PMID- 20028851
TI  - The nicotinamide phosphoribosyltransferase: a molecular link between metabolism,
      inflammation, and cancer.
AB  - Beyond its well-described role in cellular metabolism, intracellular nicotinamide
      adenine dinucleotide (NAD) levels have been shown to affect the enzymatic
      activity of a series of NAD-dependent enzymes, influencing biological responses
      such as cell survival and inflammation. Nicotinamide phosphoribosyl transferase
      activity has been shown to be essential for maintaining adequate intracellular
      NAD levels, suggesting that this enzyme may in fact play a central role in
      modulating the activity of a wide range of NAD-dependent enzymes. Several recent
      observations concur with this hypothesis and suggest that by regulating NAD
      availability, Nampt is able to control both cell viability and the inflammatory
      response. Nampt may thus represent a novel pharmacological target with valuable
      anti-inflammatory and antitumor properties.

PMID- 20028852
TI  - Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine
      and cysteine.
AB  - Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and
      are potent inhibitors of T-cell-mediated antitumor immunity. Their inhibitory
      activity is attributed to production of arginase, reactive oxygen species,
      inducible nitric oxide synthase, and interleukin-10. Here we show that MDSCs also
      block T-cell activation by sequestering cystine and limiting the availability of
      cysteine. Cysteine is an essential amino acid for T-cell activation because T
      cells lack cystathionase, which converts methionine to cysteine, and because they
      do not have an intact xc- transporter and therefore cannot import cystine and
      reduce it intracellularly to cysteine. T cells depend on antigen-presenting cells
      (APC), such as macrophages and dendritic cells, to export cysteine, which is
      imported by T cells via their ASC neutral amino acid transporter. MDSCs express
      the xc- transporter and import cystine; however, they do not express the ASC
      transporter and do not export cysteine. MDSCs compete with APC for extracellular
      cystine, and in the presence of MDSCs, APC release of cysteine is reduced,
      thereby limiting the extracellular pool of cysteine. In summary, MDSCs consume
      cystine and do not return cysteine to their microenvironment, thereby depriving T
      cells of the cysteine they require for activation and function.

PMID- 20028853
TI  - Small-molecule inhibitors of phosphatidylinositol 3-kinase/Akt signaling inhibit
      Wnt/beta-catenin pathway cross-talk and suppress medulloblastoma growth.
AB  - Activation of the beta-catenin and receptor kinase pathways occurs often in
      medulloblastoma, the most common pediatric malignant brain tumor. In this study,
      we show that molecular cross-talk between the beta-catenin and
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways is crucial to sustain
      medulloblastoma pathophysiology. Constitutive activation of phosphoinositide
      dependent protein kinase 1 (PDK1), Akt, and phosphorylation of [corrected]
      glycogen synthase kinase 3beta (GSK-3beta) was detected by immunohistochemistry
      in all primary medulloblastomas examined (n = 41). Small-molecule inhibitors
      targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by
      activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic
      retention of beta-catenin and reduced expression of its target genes cyclin D1
      and c-Myc. The PDK1 inhibitor OSU03012 induced mitochondrial-dependent apoptosis
      of medulloblastoma cells and enhanced the cytotoxic effects of chemotherapeutic
      drugs in a synergistic or additive manner. In vivo, OSU03012 inhibited the growth
      of established medulloblastoma xenograft tumors in a dose-dependent manner and
      augmented the antitumor effects of mammalian target of rapamycin inhibitor CCI
      779. These findings demonstrate the importance of cross-talk between the PI3K/Akt
      and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt
      signaling pathway as a therapeutic target in treatment of this disease.

PMID- 20028854
TI  - AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian
      target of rapamycin kinase inhibitor with in vitro and in vivo antitumor
      activity.
AB  - The mammalian target of rapamycin (mTOR) kinase forms two multiprotein complexes,
      mTORC1 and mTORC2, which regulate cell growth, cell survival, and autophagy.
      Allosteric inhibitors of mTORC1, such as rapamycin, have been extensively used to
      study tumor cell growth, proliferation, and autophagy but have shown only limited
      clinical utility. Here, we describe AZD8055, a novel ATP-competitive inhibitor of
      mTOR kinase activity, with an IC50 of 0.8 nmol/L. AZD8055 showed excellent
      selectivity (approximately 1,000-fold) against all class I phosphatidylinositol 3
      kinase (PI3K) isoforms and other members of the PI3K-like kinase family.
      Furthermore, there was no significant activity against a panel of 260 kinases at
      concentrations up to 10 micromol/L. AZD8055 inhibits the phosphorylation of
      mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2
      substrate AKT and downstream proteins. The rapamycin-resistant T37/46
      phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in
      significant inhibition of cap-dependent translation. In vitro, AZD8055 potently
      inhibits proliferation and induces autophagy in H838 and A549 cells. In vivo,
      AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and
      phosphorylated AKT at plasma concentrations leading to tumor growth inhibition.
      Notably, AZD8055 results in significant growth inhibition and/or regression in
      xenografts, representing a broad range of human tumor types. AZD8055 is currently
      in phase I clinical trials.

PMID- 20028855
TI  - Central role of IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of
      interleukin-12-mediated antitumor immunity.
AB  - Sustained intratumoral delivery of interleukin-12 (IL-12) and granulocyte
      macrophage colony-stimulating factor induces tumor regression via restoration of
      tumor-resident CD8+ T-effector/memory cell cytotoxicity and subsequent repriming
      of a secondary CD8+ T-effector cell response in tumor-draining lymph nodes
      (TDLN). However, treatment-induced T-effector activity is transient and is
      accompanied with a CD4+ CD25+ Foxp3+ T-suppressor cell rebound. Molecular and
      cellular changes in posttherapy tumor microenvironment and TDLN were monitored to
      elucidate the mechanism of counterregulation. Real-time PCR analysis revealed a 5
      fold enhancement of indoleamine 2,3-dioxygenase (IDO) expression in the tumor and
      the TDLN after treatment. IDO induction required IFNgamma and persisted for up to
      7 days. Administration of the IDO inhibitor D-1-methyl tryptophan concurrent with
      treatment resulted in a dramatic enhancement of tumor regression. Enhanced
      efficacy was associated with a diminished T-suppressor cell rebound, revealing a
      link between IDO activity and posttherapy regulation. Further analysis
      established that abrogation of the regulatory counterresponse resulted in a 10
      fold increase in the intratumoral CD8+ T-cell to CD4+ Foxp3+ T-cell ratio. The
      ratio of proliferating CD8+ T-effector to CD4+ Foxp3+ T-suppressor cells was
      prognostic for efficacy of tumor suppression in individual mice. IFNgamma
      dependent IDO induction and T-suppressor cell expansion were primarily driven by
      IL-12. These findings show a critical role for IDO in the regulation of IL-12
      mediated antitumor immune responses.

PMID- 20028856
TI  - CCL2 blockade augments cancer immunotherapy.
AB  - Altering the immunosuppressive microenvironment that exists within a tumor will
      likely be necessary for cancer vaccines to trigger an effective antitumor
      response. Monocyte chemoattractant proteins (such as CCL2) are produced by many
      tumors and have both direct and indirect immunoinhibitory effects. We
      hypothesized that CCL2 blockade would reduce immunosuppression and augment
      vaccine immunotherapy. Anti-murine CCL2/CCL12 monoclonal antibodies were
      administered in three immunotherapy models: one aimed at the human papillomavirus
      E7 antigen expressed by a non-small cell lung cancer (NSCLC) line, one targeted
      to mesothelin expressed by a mesothelioma cell line, and one using an adenovirus
      expressing IFN-alpha to treat a nonimmunogenic NSCLC line. We evaluated the
      effect of the combination treatment on tumor growth and assessed the mechanism of
      these changes by evaluating cytotoxic T cells, immunosuppressive cells, and the
      tumor microenvironment. Administration of anti-CCL2/CCL12 antibodies along with
      the vaccines markedly augmented efficacy with enhanced reduction in tumor volume
      and cures of approximately half of the tumors. The combined treatment generated
      more total intratumoral CD8+ T cells that were more activated and more antitumor
      antigen-specific, as measured by tetramer evaluation. Another important potential
      mechanism was reduction in intratumoral T regulatory cells. CCL2 seems to be a
      key proximal cytokine mediating immunosuppression in tumors. Its blockade
      augments CD8+ T-cell immune response to tumors elicited by vaccines via
      multifactorial mechanisms. These observations suggest that combining CCL2
      neutralization with vaccines should be considered in future immunotherapy trials.

PMID- 20028857
TI  - Alternative splicing of the cyclin D1 proto-oncogene is regulated by the RNA
      binding protein Sam68.
AB  - Human cyclin D1 is expressed as two isoforms derived by alternate RNA splicing,
      termed D1a and D1b, which differ for the inclusion of intron 4 in the D1b mRNA.
      Both isoforms are frequently upregulated in human cancers, but cyclin D1b
      displays relatively higher oncogenic potential. The splicing factors that
      regulate alternative splicing of cyclin D1b remain unknown despite the likelihood
      that they contribute to cyclin D1 oncogenicity. In this study, we report that
      Sam68, an RNA-binding protein frequently overexpressed in prostate cancer cells,
      enhances splicing of cyclin D1b and supports its expression in prostate cancer
      cells. Chromatin immunoprecipitation and RNA coimmunoprecipitation experiments
      showed that Sam68 is recruited to the human CCND1 gene encoding cyclin D1 and
      that it binds to cyclin D1 mRNA. Transient overexpression and RNAi knockdown
      experiments indicated that Sam68 acts to enhance endogenous expression of cyclin
      D1b. Minigene reporter assays showed that Sam68 directly affected alternative
      splicing of CCND1 message, with a preference for the A870 allele that is known to
      favor cyclin D1b splicing. Sam68 interacted with the proximal region of intron 4,
      and its binding correlated inversely with recruitment of the spliceosomal
      component U1-70K. Sam68-mediated splicing was modulated by signal transduction
      pathways that elicit phosphorylation of Sam68 and regulate its affinity for CCND1
      intron 4. Notably, Sam68 expression positively correlates with levels of cyclin
      D1b, but not D1a, in human prostate carcinomas. Our results identify Sam68 as the
      first splicing factor to affect CCND1 alternative splicing in prostate cancer
      cells, and suggest that increased levels of Sam68 may stimulate cyclin D1b
      expression in human prostate cancers.

PMID- 20028858
TI  - Changes in the mouse estrus cycle in response to BRCA1 inactivation suggest a
      potential link between risk factors for familial and sporadic ovarian cancer.
AB  - Menstrual cycle activity is the most important risk factor for sporadic serous
      ovarian carcinoma, whereas a germ-line mutation in BRCA1 is the most important
      risk factor for the familial form. Given the rarity of BRCA1 mutations in
      sporadic ovarian cancers, we hypothesized that BRCA1 influences the menstrual
      cycle in a way that mimics the factors underlying sporadic ovarian cancer
      predisposition, making BRCA1 mutations redundant in such cancers. We compared the
      length of each phase of the estrus cycle (equivalent to the human menstrual
      cycle) and of circulating levels of estradiol in control mice and in mice
      carrying a Brca1 mutation in their ovarian granulosa cells, two thirds of which
      develop ovarian or uterine epithelial tumors. We also compared the length of the
      different phases of the cycle in mutants that subsequently developed tumors with
      those in mutants that remained tumor-free. Mutant mice as well as oophorectomized
      wild-type mice harboring mutant ovarian grafts showed a relative increase in the
      average length of the proestrus phase of the estrus cycle, which corresponds to
      the estrogen-dominated follicular phase of the human menstrual cycle. Total
      circulating levels of estradiol were also increased in mutant mice injected with
      pregnant mare serum gonadotropins. The relative increase in proestrus length was
      highest in mutant mice that subsequently developed reproductive epithelial
      tumors. We conclude that loss of a functional Brca1 increases murine ovarian
      epithelial tumor predisposition by increasing estrogen stimulation in the absence
      of progesterone, recapitulating conditions associated with sporadic ovarian
      cancer predisposition in humans.

PMID- 20028859
TI  - Evaluation of microRNA expression profiles that may predict recurrence of
      localized stage I non-small cell lung cancer after surgical resection.
AB  - Prognostic markers that can predict the relapse of localized non-small cell lung
      cancer (NSCLC) have yet to be defined. We surveyed expression profiles of
      microRNA (miRNA) in stage I NSCLC to identify patterns that might predict
      recurrence after surgical resection of this common deadly cancer. Small RNAs
      extracted from formalin-fixed and paraffin-embedded tissues were hybridized to
      locked nucleic acid probes against 752 human miRNAs (representing 82% of the
      miRNAs in the miRBase 13.0 database) to obtain expression profiles for 37 cases
      with recurrence and 40 cases without recurrence (with clinical follow-up for at
      least 32 months). Differential expression between the two case groups was
      detected for 49% of the miRNAs (Wilcoxon rank sum test; P<0.01). The performance
      of expression profiles at differentiating the two case groups was assessed by
      leave-one-out and Monte Carlo cross-validations. In leave-one-out cross
      validation using support vector machines- or top-scoring gene pair classifier
      methods, which looked for six- or two-miRNA-based classifiers, the identified
      miRNA expression pattern predicted recurrence with an accuracy of 70% and 83%,
      and hazard ratio of 3.6 [95% confidence interval (95% CI), 1.8-7.1] and 9.0 (95%
      CI, 4.4-18.2), respectively. Mean accuracy in Monte Carlo cross-validation using
      1,000 random 60-17 splits was 69% (95% CI, 68-70) and 72% (95% CI, 71-72),
      respectively. The specific miRNAs mir-200b*, mir-30c-1*, mir-510, mir-630, mir
      657, and mir-146b-3p and mir-124*, mir-585, and mir-708, respectively,
      represented most commonly among the 1,000 classifiers identified in Monte Carlo
      cross-validation by the two methods. MiRNAs mir-488, mir-503, and mir-647 were
      identified as potential reference miRNAs for future studies, based on the
      stability of their expression patterns across the 77 cases and the two case
      groups. Our findings reinforce efforts to profile miRNA expression patterns for
      better prognostication of stage I NSCLC.

PMID- 20028860
TI  - Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells.
AB  - Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the
      KIT or PDGFRA receptor tyrosine kinase genes. Although >85% of GIST patients
      treated with the small-molecule inhibitor imatinib mesylate (Gleevec) achieve
      disease stabilization, complete remissions are rare and a substantial proportion
      of patients develop resistance to imatinib over time. Upregulation of soluble,
      non-chromatin-bound histone H2AX has an important role in imatinib-induced
      apoptosis of GIST cells. Additionally, H2AX levels in untreated GIST are
      maintained at low levels by a pathway that involves KIT, phosphoinositide 3
      kinase, and the ubiquitin-proteasome system. In this study, we asked whether
      bortezomib-mediated inhibition of the ubiquitin-proteasome machinery could lead
      to upregulation of histone H2AX and GIST cell death. We show that bortezomib
      rapidly triggers apoptosis in GIST cells through a combination of mechanisms
      involving H2AX upregulation and loss of KIT protein expression. Downregulation of
      KIT transcription was an underlying mechanism for bortezomib-mediated inhibition
      of KIT expression. In contrast, the nuclear factor-kappaB signaling pathway did
      not seem to play a major role in bortezomib-induced GIST cell death.
      Significantly, we found that bortezomib would induce apoptosis in two imatinib
      resistant GIST cell lines as well as a short-term culture established from a
      primary imatinib-resistant GIST. Collectively, our results provide a rationale to
      test the efficacy of bortezomib in GIST patients with imatinib-sensitive or 
      resistant tumors.

PMID- 20028861
TI  - VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription
      repressor, is a putative tumor suppressor.
AB  - Lymphoid-enhancing factor/T-cell factors (LEF1/TCF) are a high-mobility group of
      transcriptional factors that play essential roles in cell fate determination
      during early embryogenesis and ontogenesis. Aberrant activations of LEF1/TCF
      mediated transcription have been implicated in a variety of malignancies. Our
      recent studies on vertebrate embryogenesis identified Xom, a homeobox protein of
      the bone morphogenetic protein 4 pathway, as a novel LEF/TCF-associated
      transcriptional modulator. Here, we report that VentX, a human Xom homologue, is
      a LEF/TCF-associated inhibitor of canonical Wnt/beta-catenin signaling and a
      negative regulator of cell proliferation. VentX is predominantly expressed in
      hematopoietic cells, and its expression is significantly downregulated in chronic
      lymphocytic leukemia. Altered expression of VentX is associated with
      corresponding changes of LEF/TCF target oncogenes such as cyclin D1, suggesting a
      potential role of VentX in the clinical behavior of hematopoietic malignancies.

PMID- 20028862
TI  - Twenty-first annual Pezcoller Symposium: Unconventional Therapeutic Targets in
      Cancer.

PMID- 20028863
TI  - Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback
      regulators of hypoxia-inducible factors.
AB  - Adaptive responses to hypoxia in tumors are transcriptionally regulated by the
      hypoxia inducible factors (HIF-1alpha/HIF-2alpha), which are tightly controlled
      by the HIF-prolyl hydroxylases (PHD). Hypoxia induces expression of the PHD2 and
      PHD3 proteins in tumors but the pathobiological significance of these events is
      uncertain. Here, we show that PHD2 and PHD3 induction acts within a negative
      feedback loop to limit the hypoxic HIF response. In glioblastomas, PHD2 and PHD3
      are hypoxia-inducible in vitro and expressed in hypoxic areas of tumors in vivo.
      Comparison with other PHDs revealed distinct cytoplasmatic and nuclear
      localization patterns of PHD2 and PHD3. Gain and loss of function experiments
      defined PHD2 and PHD3 as HIF target genes that remained operative even at low
      oxygen concentrations. We found that increased PHD levels could compensate for
      reduced oxygen availability to regulate the HIF response. This negative feedback
      loop protected tumor cells against hypoxia-induced cell death, functionally
      implicating this pathway in the control of the tumor-suppressive components of
      the HIF system in glioblastoma. Moreover, PHD inhibition facilitated cell death
      induction by staurosporine or tumor necrosis factor-related apoptosis-inducing
      ligand, hinting at a more general protective role of PHD in the regulation of
      cell viability. In summary, our findings recognize the PHD/HIF regulatory axis as
      a novel therapeutic target to disable a tumor's ability to adjust to hypoxic
      conditions and control cell survival, helping to potentially overcome therapeutic
      cell death resistance in glioblastomas.

PMID- 20028864
TI  - Obesity and breast cancer: progress to understanding the relationship.
AB  - Epidemiological evidence supports a correlation between obesity and breast cancer
      in women. AMP-activated protein kinase (AMPK) is recognized to be a master
      regulator of energy homeostasis. One of its actions is to phosphorylate and
      inhibit the actions of cAMP-responsive element binding protein (CREB)-regulated
      transcription coactivator 2 (CRTC2). In postmenopausal women, the CREB-dependent
      regulation of aromatase is a crucial determinant of breast tumor formation
      through local production of estrogens. We report here that the regulation of
      aromatase expression in the breast by AMPK and CRTC2, in response to the altered
      adipokine milieu associated with obesity, provides an important link between
      obesity and breast cancer risk.

PMID- 20028865
TI  - Diagnosing cervical cancer and high-grade precursors by HPV16 transcription
      patterns.
AB  - Infections with high-risk human papillomaviruses (HPV), mainly HPV type 16, can
      cause malignant transformation of the human cervical epithelium and the
      development of cervical cancer (CxCa). A rapid and precise diagnosis of the
      precancerous lesions by conventional cytology or HPV DNA tests remains difficult
      and often leads to overtreatment. We quantitatively analyzed the HPV16
      transcriptome of 80 HPV16 DNA-positive cervical scrapes classified as mild
      cytologic grade, including no intraepithelial lesion or malignancy (NIL/M;
      normal, n=25) and low-grade squamous intraepithelial lesion (LSIL; n=24), and
      severe cytologic grade, including high-grade squamous intraepithelial lesion
      (HSIL; n=24) and CxCa (n=7), with novel nucleic acid sequence-based amplification
      Luminex assays. In severe lesions, HPV16 E6*II and E1C encoding transcripts were
      strongly upregulated, whereas spliced E1[SYMBOL: SEE TEXT]E4 and L1 encoding
      transcripts were markedly downregulated. Using a combination of the four marker
      transcripts, 100% of CxCa and 67% of HSIL cases were correctly identified as
      severe, and 74% of LSIL and 92% of NIL/M samples as mild cytologic grade.
      Compared with a commercially available HPV E6/E7 mRNA assay, the specificity of
      the marker combination for discriminating severe and mild cytologic lesions
      increased from 23% to 83%. In conclusion, we identified a novel HPV16 RNA pattern
      for grading of cervical lesions with a potentially high diagnostic value for the
      primary screening of CxCa precursors and the triage of cervical lesions.

PMID- 20028866
TI  - Genetically engineered Salmonella typhimurium as an imageable therapeutic probe
      for cancer.
AB  - Tumor-targeting bacteria have been studied in terms of their ability to visualize
      the infection pathway (through imaging probes) or to carry therapeutic molecules
      to tumors. To integrate these monitoring and therapeutic functions, we engineered
      attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'
      diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express
      reporter genes. We successfully visualized the therapeutic process with these
      engineered bacteria in mice and found that they often mediated complete tumor (CT
      26) eradication on cytotoxic gene induction. Furthermore, treatment with the
      engineered bacteria markedly suppressed metastatic tumor growth.

PMID- 20028867
TI  - OTX2 is critical for the maintenance and progression of Shh-independent
      medulloblastomas.
AB  - OTX2 is a developmentally regulated transcription factor involved in early
      morphogenesis of the central nervous system. This gene is amplified and
      overexpressed in medulloblastoma cell lines, but the nature and extent of its
      genetic alterations in primary tumors have not been evaluated. Analysis of a
      large cohort of primary medulloblastomas revealed frequent focal copy number gain
      of a region minimally containing OTX2 as a single gene. OTX2 copy number gain was
      restricted to tumor subtypes that did not express a molecular signature of Wnt or
      Shh pathway activation. FISH analysis revealed copy number gain in a subset of
      cells within medulloblastoma samples, suggesting a late event in tumor
      progression. Gain of OTX2 copy number was associated with the presence of
      anaplastic histologic features and shorter survival in medulloblastoma patients.
      In support of a functional role, ectopic OTX2 expression enhanced proliferation
      and tumorigenicity of immortalized primary cells, whereas OTX2 knockdown in
      medulloblastoma cells prolonged the survival of animals bearing xenograft tumors.
      Mechanistic investigations revealed upregulation of MYC as a potential mechanism
      whereby OTX2 promotes tumor progression. Our findings define OTX2 as an important
      oncogenic driver in medulloblastoma.

PMID- 20028868
TI  - Systems biologists seek fuller integration of systems biology approaches in new
      cancer research programs.
AB  - Systems biology takes an interdisciplinary approach to the systematic study of
      complex interactions in biological systems. This approach seeks to decipher the
      emergent behaviors of complex systems rather than focusing only on their
      constituent properties. As an increasing number of examples illustrate the value
      of systems biology approaches to understand the initiation, progression, and
      treatment of cancer, systems biologists from across Europe and the United States
      hope for changes in the way their field is currently perceived among cancer
      researchers. In a recent EU-US workshop, supported by the European Commission,
      the German Federal Ministry for Education and Research, and the National Cancer
      Institute of the NIH, the participants discussed the strengths, weaknesses,
      hurdles, and opportunities in cancer systems biology.

PMID- 20028869
TI  - Elimination of human lung cancer stem cells through targeting of the stem cell
      factor-c-kit autocrine signaling loop.
AB  - Cancer stem cells (CSC) are thought to be responsible for tumor initiation and
      tumor regeneration after chemotherapy. Previously, we showed that chemotherapy of
      non-small cell lung cancer (NSCLC) cells lines can select for outgrowth of highly
      tumorigenic and metastatic CSCs. The high malignancy of lung CSCs was associated
      with an efficient cytokine network. In this study, we provide evidence that
      blocking stem cell factor (SCF)-c-kit signaling is sufficient to inhibit CSC
      proliferation and survival promoted by chemotherapy. CSCs were isolated from
      NSCLC cell lines as tumor spheres under CSC-selective conditions and their stem
      properties were confirmed. In contrast to other tumor cells, CSCs expressed c-kit
      receptors and produced SCF. Proliferation of CSCs was inhibited by SCF
      neutralizing antibodies or by imatinib (Gleevec), an inhibitor of c-kit. Although
      cisplatin treatment eliminated the majority of tumor cells, it did not eliminate
      CSCs, whereas imatinib or anti-SCF antibody destroyed CSCs. Significantly,
      combining cisplatin with imatinib or anti-SCF antibody prevented the growth of
      both tumor cell subpopulations. Our findings reveal an important role for the SCF
      c-kit signaling axis in self-renewal and proliferation of lung CSCs, and they
      suggest that SCF-c-kit signaling blockade could improve the antitumor efficacy of
      chemotherapy of human NSCLC.

PMID- 20028870
TI  - Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and
      invasiveness.
AB  - Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain
      tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive
      and malignant state. Here we show that hypoxia increases Notch1 activation, which
      in turn induces the expression of transient receptor potential 6 (TRPC6) in
      primary samples and cell lines derived from GBM. TRPC6 is required for the
      development of the aggressive phenotype because knockdown of TRPC6 expression
      inhibits glioma growth, invasion, and angiogenesis. Functionally, TRPC6 causes a
      sustained elevation of intracellular calcium that is coupled to the activation of
      the calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Pharmacologic
      inhibition of the calcineurin-NFAT pathway substantially reduces the development
      of the malignant GBM phenotypes under hypoxia. Clinically, expression of TRPC6
      was elevated in GBM specimens in comparison with normal tissues. Collectively,
      our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro
      and in vivo and that TRPC6 may be a promising therapeutic target in the treatment
      of human GBM.

PMID- 20028871
TI  - Definition of microRNAs that repress expression of the tumor suppressor gene
      FOXO1 in endometrial cancer.
AB  - Endometrial cancer is the most common malignancy of the lower female reproductive
      tract. The tumor suppressor FOXO1 is downregulated in endometrial cancer compared
      with normal endometrium but the underlying mechanisms are not well understood.
      Using microRNA (miR) target prediction algorithms, we identified several miRs
      that potentially bind the 3'-untranslated region of FOXO1 transcripts. Expression
      profiling of normal and malignant endometrial samples by quantitative real-time
      PCR and Northern blot analysis revealed an inverse correlation between the levels
      of FOXO1 protein and the abundance of several of the in silico-predicted miRs,
      suggesting that loss of FOXO1 expression in endometrial cancer may be mediated by
      miRs. To determine the role of candidate miRs, we used the endometrial cancer
      cell lines HEC-1B and Ishikawa, which express FOXO1 at high and low levels,
      respectively. Expression of miR-9, miR-27, miR-96, miR-153, miR-182, miR-183, or
      miR-186, but not miR-29a, miR-128, miR-152, or miR-486 mimetics in HEC-1B cells
      was sufficient to significantly reduce the abundance of FOXO1. Conversely, FOXO1
      expression was efficiently restored in the Ishikawa cell line upon simultaneous
      inhibition of miR-9, miR-27, miR-96, miR-153, miR-183, and miR-186. Moreover,
      induction of FOXO1 in Ishikawa cells by miR inhibitors was accompanied by G1 cell
      cycle arrest and cell death, and was attenuated by the small interfering RNA
      mediated downregulation of FOXO1 expression. Our findings identify several miRs
      overexpressed in endometrial cancer that function in concert to repress FOXO1
      expression. Further, aberrant miR expression results in deregulated cell cycle
      control and impaired apoptotic responses, and thus, may be central to endometrial
      tumorigenesis.

PMID- 20028872
TI  - Imaging the unfolded protein response in primary tumors reveals microenvironments
      with metabolic variations that predict tumor growth.
AB  - Cancer cells exist in harsh microenvironments that are governed by various
      factors, including hypoxia and nutrient deprivation. These microenvironmental
      stressors activate signaling pathways that affect cancer cell survival. While
      others have previously measured microenvironmental stressors in tumors, it
      remains difficult to detect the real-time activation of these downstream
      signaling pathways in primary tumors. In this study, we developed transgenic mice
      expressing an X-box binding protein 1 (XBP1)-luciferase construct that served as
      a reporter for endoplasmic reticulum (ER) stress and as a downstream response for
      the tumor microenvironment. Primary mammary tumors arising in these mice
      exhibited luciferase activity in vivo. Multiple tumors arising in the same mouse
      had distinct XBP1-luciferase signatures, reflecting either higher or lower levels
      of ER stress. Furthermore, variations in ER stress reflected metabolic and
      hypoxic differences between tumors. Finally, XBP1-luciferase activity correlated
      with tumor growth rates. Visualizing distinct signaling pathways in primary
      tumors reveals unique tumor microenvironments with distinct metabolic signatures
      that can predict for tumor growth.

PMID- 20028873
TI  - Potentiation of temozolomide cytotoxicity by inhibition of DNA polymerase beta is
      accentuated by BRCA2 mutation.
AB  - Base excision repair (BER) plays a critical role in the repair of bases damaged
      by oxidative metabolism or alkylating agents, such as those commonly used in
      cancer therapy. Incomplete BER generates intermediates that require activation of
      homology-dependent DNA repair to resolve. We investigated the effects of
      lithocholic acid (LCA), an inhibitor of the key BER enzyme DNA polymerase beta
      (pol beta), in cells deficient in expression of the homology-dependent repair
      factor BRCA2. In vitro studies show that LCA suppresses the DNA polymerase and 5'
      deoxyribose phosphate lyase activities of DNA pol beta by preventing the
      formation of a stable pol beta-DNA complex, reducing BER effectiveness.
      Cytotoxicity assays based on colony formation revealed that LCA exhibits
      synergism with the alkylating agent temozolomide, which engages BER through DNA
      methylation, and that the degree of synergism is increased in cells lacking
      functional BRCA2. BRCA2-deficient cells also showed heightened susceptibility to
      both LCA and temozolomide individually. The potentiation of temozolomide
      cytotoxicity by LCA owes to the conversion of single-stranded DNA breaks
      generated through incomplete BER of methylated nucleotides into double-stranded
      breaks during DNA replication, as indicated by gammaH2AX immunofluorescence.
      Death seems to be induced in cotreated cells through an accumulation of
      persistent double-stranded DNA breaks. Mutations of the BRCA2 gene have been
      extensively characterized and are present in various cancers, implying that
      inhibition of BER may offer a means to augment tumor selectivity in the use of
      conventional cancer therapies.

PMID- 20028876
TI  - Fraud: just say no!

PMID- 20028874
TI  - Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab
      therapy.
AB  - One arising challenge in the treatment of breast cancer is the development of
      therapeutic resistance to trastuzumab, an antibody targeting the human epidermal
      growth factor receptor-2 (HER2), which is frequently amplified in breast cancers.
      In this study, we provide evidence that elevated level of the receptor tyrosine
      kinase Eph receptor A2 (EphA2) is an important contributor to trastuzumab
      resistance. In a screen of a large cohort of human breast cancers, we found that
      EphA2 overexpression correlated with a decrease in disease-free and overall
      survival of HER2-overexpressing patients. Trastuzumab-resistant cell lines
      overexpressed EphA2, whereas inhibiting EphA2 restored sensitivity to trastuzumab
      treatment in vivo. Notably, trastuzumab treatment could promote EphA2
      phosphorylation by activating Src kinase, leading in turn to an amplification of
      phosphoinositide 3-kinase/Akt and mitogen-activated protein kinase signaling in
      resistant cells. Our findings offer mechanistic insights into the basis for
      trastuzumab resistance and rationalize strategies to target EphA2 as a tactic to
      reverse trastuzumab resistance.

PMID- 20028875
TI  - DNA damage drives an activin a-dependent induction of cyclooxygenase-2 in
      premalignant cells and lesions.
AB  - Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the synthesis of
      prostaglandins. Its overexpression induces numerous tumor-promoting phenotypes
      and is associated with cancer metastasis and poor clinical outcome. Although COX
      2 inhibitors are promising chemotherapeutic and chemopreventative agents for
      cancer, the risk of significant cardiovascular and gastrointestinal complications
      currently outweighs their potential benefits. Systemic complications of COX-2
      inhibition could be avoided by specifically decreasing COX-2 expression in
      epithelial cells. To that end, we have investigated the signal transduction
      pathway regulating the COX-2 expression in response to DNA damage in breast
      epithelial cells. In variant human mammary epithelial cells that have silenced
      p16 (vHMEC), double-strand DNA damage or telomere malfunction results in a p53-
      and activin A-dependent induction of COX-2 and continued proliferation. In
      contrast, telomere malfunction in HMEC with an intact p16/Rb pathway induces cell
      cycle arrest. Importantly, in ductal carcinoma in situ lesions, high COX-2
      expression is associated with high gammaH2AX, TRF2, activin A, and telomere
      malfunction. These data show that DNA damage and telomere malfunction can have
      both cell-autonomous and cell-nonautonomous consequences and can provide a novel
      mechanism for the propagation of tumorigenesis.

PMID- 20028877
TI  - Fat and energy economy in hypo- and hyperthyroidism are not the mirror image of
      one another.

PMID- 20028878
TI  - Lesbian/bisexual mothers and intimate partner violence: help seeking in the
      context of social and legal vulnerability.
AB  - Mothers in same-sex relationships face unique challenges when help seeking for
      intimate partner violence (IPV). Formal helping systems often invalidate their
      family relationships, leaving them vulnerable and distrustful when help seeking.
      To better understand their experiences, the authors interviewed 24
      lesbian/bisexual mothers who were either in or had left abusive same-sex
      relationships. Increasing severity of violence, effects of violence on children
      and families, and "being tired" influenced their definitions of the situation.
      Decisions to seek formal help appeared to be influenced by their support from
      informal networks and perceived stigma related to the intersection of IPV and
      being lesbian or bisexual.

PMID- 20028879
TI  - Multiple cystlike lung lesions in the adult.

PMID- 20028880
TI  - Systemic arterial embolization in patients with hemoptysis: initial experience
      with ethylene vinyl alcohol copolymer in 15 cases.
AB  - OBJECTIVE: The purpose of this study was a preliminary evaluation of the use of
      ethylene vinyl alcohol copolymer to treat patients with hemoptysis of systemic
      arterial origin. MATERIALS AND METHODS: We reviewed the cases of 15 consecutively
      registered patients (10 men, five women; mean age, 53.7 years) who underwent
      endovascular administration of ethylene vinyl alcohol copolymer in the management
      of hemoptysis. The indications, immediate control of hemoptysis, and clinical
      tolerability were analyzed. RESULTS: The indications for embolization were mainly
      early recurrence of hemoptysis with reperfusion of systemic arteries in seven
      cases; unstable microcatheter in two cases; large ectopic bronchial artery in two
      cases; and, in one case each, bronchial arterial bleeding through a small
      anastomotic network, aneurysm of the left internal thoracic artery in a patient
      with invasive aspergillosis, a potentially risky connection between the bronchial
      and right coronary arteries, and occlusion of a systemic artery due to Pryce type
      1 intralobar lung sequestration. Hemoptysis was controlled in all but one case
      and did not recur in the other 14 cases. The injection procedure was well
      tolerated. CONCLUSION: Ethylene vinyl alcohol copolymer embolization for
      hemoptysis of systemic arterial origin is feasible. The agent seems beneficial in
      the care of patients with recurrent hemoptysis after previous bronchial arterial
      embolization, patients who would be at high risk during embolization with
      microparticles, and patients who need embolization of large systemic arteries
      through small-caliber anastomoses.

PMID- 20028881
TI  - Prospective ECG-triggered CT angiography of the thoracic aorta in patients with
      atrial fibrillation or accelerated heart rates: feasibility and image quality.
AB  - OBJECTIVE: The objective of our study was to prospectively investigate the
      feasibility and image quality of and to calculate the radiation dose estimates
      for CT angiography (CTA) of the thoracic aorta in patients with atrial
      fibrillation or accelerated heart rates using prospective ECG-triggered
      sequential dual-source data acquisition in end-systole. CONCLUSION: Prospective
      ECG-gated sequential dual-source CTA of the thoracic aorta is feasible despite
      heart rates>80 beats per minute or atrial fibrillation, making motion-free
      imaging of the thoracic aorta possible at a considerably low radiation dose.

PMID- 20028882
TI  - Lesion size inaccuracies in digital mammography.
AB  - OBJECTIVE: We show with both a clinical case and measurements using the American
      College of Radiology mammography phantom that some digital mammography
      acquisition and image display combinations lead to both marked over- and
      underestimation of lesion sizes on geometrically magnified images. CONCLUSION:
      The results of this study indicate that the accuracy of lesion size measurements
      in all magnification modes should be a routine quality control acceptance test
      with each acquisition-display system combination in digital mammography.

PMID- 20028883
TI  - Scar endometrioma: too unusual to be remembered?

PMID- 20028884
TI  - Imaging manifestations of Niemann-Pick disease type B.
AB  - OBJECTIVE: The purpose of this article is to illustrate the various imaging
      manifestations of Niemann-Pick disease type B using various imaging techniques
      emphasizing cross-sectional imaging. CONCLUSION: Niemann-Pick disease type B is a
      multisystem disease that affects the pulmonary, cardiovascular, abdominal, and
      skeletal systems. Cross-sectional imaging is well suited for detecting and
      assessing the various manifestations of this disease, which can be highly
      suggestive of the diagnosis when seen in combination.

PMID- 20028885
TI  - Digital mammography leads to more short-term follow-up.

PMID- 20028886
TI  - Uncommon occupational lung diseases: high-resolution CT findings.
AB  - OBJECTIVE: The purpose of this article is to describe the high-resolution CT
      (HRCT) features of uncommon occupational lung diseases. CONCLUSION: HRCT plays an
      increasing role in the evaluation of occupational lung diseases. We present
      several cases of unusual occupational lung diseases and their HRCT findings. The
      diseases studied were siderosis, talcosis, berylliosis, calcicosis,
      hypersensitivity pneumonitis (due to wheat flour and isocyanates), and Ardystil
      syndrome. The characteristic HRCT findings together with clinical features and
      related occupational history improve the diagnostic accuracy of these diseases.

PMID- 20028887
TI  - Dual-source dual-energy MDCT of pancreatic adenocarcinoma: initial observations
      with data generated at 80 kVp and at simulated weighted-average 120 kVp.
AB  - OBJECTIVE: The purpose of this study was to determine whether the conspicuity of
      malignant tumors of the pancreas at dual-source dual-energy CT is better with 80
      kVp acquisition than with 120-kVp acquisition simulated with a weighted average.
      MATERIALS AND METHODS: Fifteen patients with pancreatic adenocarcinoma underwent
      contrast-enhanced dual-source dual-energy CT. The abdominal diameter of all
      patients was 35 cm or less. Data were reconstructed as a weighted average of the
      140- and 80-kVp acquisitions, simulating 120 kVp, and as a pure 80-kVp data set.
      A region-of-interest cursor was placed within the tumor and the adjacent normal
      parenchyma, and attenuation differences and contrast-to-noise ratios were
      calculated for pancreatic tumors at 80 kVp and with the weighted-average
      acquisition. The 80-kVp and weighted-average images were subjectively compared in
      terms of lesion conspicuity, image quality, and duct visualization. An exact
      Wilcoxon's matched pairs signed rank test was used to test whether differences in
      attenuation, contrast-to-noise ratio, and subjective assessment were greater at
      80 kVp. RESULTS: The mean difference in attenuation for each pancreatic tumor and
      adjacent portion of normal pancreas was 83.27+/-29.56 (SD) HU at 80 kVp and
      49.40+/-23.00 HU at weighted-average 120 kVp. Adenocarcinoma attenuation
      differences were significantly greater at 80 kVp than at 120 kVp (p=0.00006).
      Contrast-to-noise ratio was significantly higher at 80 kVp than at 120 kVp
      (p=0.00147). Subjective analysis showed lesion conspicuity (p=0.001) and duct
      visualization (p=0.0156) were significantly better on the 80-kVp images.
      CONCLUSION: At portal venous phase dual-source dual-energy CT, the conspicuity of
      malignant tumors of the pancreas is greater at 80 kVp than with weighted-average
      acquisition.

PMID- 20028888
TI  - High-b-value diffusion-weighted imaging at 3 T to detect prostate cancer:
      comparisons between b values of 1,000 and 2,000 s/mm2.
AB  - OBJECTIVE: The objective of our study was to investigate the diagnostic
      performance of 3-T MRI of the prostate using diffusion-weighted imaging (DWI)
      with high b values (1,000 and 2,000 s/mm2) and a phased-array coil in predicting
      localized prostate cancer. MATERIALS AND METHODS: Forty-eight patients underwent
      single-shot echo-planar DWI at 3 T, followed by radical prostatectomy. DWI was
      performed at high b values of 1,000 and 2,000 s/mm2. Apparent diffusion
      coefficient (ADC) maps were analyzed by visual and quantitative assessment for
      tumor and benign tissue in the peripheral and transition zones. The visual and
      quantitative results of ADC maps obtained at b values of 1,000 and 2,000 s/mm2
      were compared with the histopathologic findings. RESULTS: To predict localized
      prostate cancer, the sensitivity of ADC maps obtained at a b value of 1,000
      versus 2,000 s/mm2 was 88% and 71%, respectively, and the accuracy was 89% and
      86% (p<0.01). The mean ADC values of tumors in both the peripheral and transition
      zones were significantly lower than those of benign tissues at both b values of
      1,000 and 2,000 s/mm2 (p<0.001). CONCLUSION: Prostate DWI performed at 3 T using
      high b values was able to improve differentiation of tumors from benign tissue.
      DWI performed using a b value of 1,000 s/mm2 was more sensitive and more accurate
      in predicting localized prostate cancer than DWI performed using a b value of
      2,000 s/mm2.

PMID- 20028889
TI  - Imaging evaluation for suspected pulmonary embolism: what do emergency physicians
      and radiologists say?
AB  - OBJECTIVE: The utility of various imaging techniques and strategies for the
      diagnosis of pulmonary embolism has been studied in randomized control trials and
      extensively described in the literature. CT and ventilation-perfusion
      scintigraphy are the mainstays of diagnosis, and MRI is emerging. The purpose of
      this study was to assess the diagnostic approach to pulmonary embolism practiced
      by emergency physicians and advised by radiologists. MATERIALS AND METHODS:
      Questionnaires were sent to emergency physicians and radiologists in
      Pennsylvania. The questions covered diagnostic strategies for the detection of
      pulmonary embolism in the usual situations and in clinical circumstances in which
      the primary imaging technique is considered less desirable. RESULTS: Sixty-two
      radiologists and 52 emergency physicians completed the survey. Ninety percent of
      radiologists and 96% of emergency physicians answered that CT was their first
      line choice for the diagnosis of pulmonary embolism. The use of ventilation
      perfusion scintigraphy increased in the care of patients with renal failure and
      allergy to iodinated contrast material. MRI was chosen infrequently. CONCLUSION:
      CT is the overwhelmingly preferred technique for the diagnosis of pulmonary
      embolism. The role of ventilation-perfusion scintigraphy increases when the use
      of iodinated contrast material is contraindicated. MRI does not seem to have an
      important role in practice.

PMID- 20028890
TI  - Dose reduction in helical CT: dynamically adjustable z-axis X-ray beam
      collimation.
AB  - OBJECTIVE: The purpose of this study was to measure the dose reduction achieved
      with dynamically adjustable z-axis collimation. MATERIALS AND METHODS: A
      commercial CT system was used to acquire CT scans with and without dynamic z-axis
      collimation. Dose reduction was measured as a function of pitch, scan length, and
      position for total incident radiation in air at isocenter, accumulated dose to
      the center of the scan volume, and accumulated dose to a point at varying
      distances from a scan volume of fixed length. Image noise was measured at the
      beginning and center of the scan. RESULTS: The reduction in total incident
      radiation in air at isocenter varied between 27% and 3% (pitch, 0.5) and 46% and
      8% (pitch, 1.5) for scan lengths of 20 and 500 mm, respectively. Reductions in
      accumulated dose to the center of the scan were 15% and 29% for pitches of 0.5
      and 1.5 for 20-mm scans. For scan lengths greater than 300 mm, dose savings were
      less than 3% for all pitches. Dose reductions 80 mm or farther from a 100-mm scan
      range were 15% and 40% for pitches of 0.5 and 1.5. With dynamic z-axis
      collimation, noise at the extremes of a helical scan was unchanged relative to
      noise at the center. Estimated reductions in effective dose were 16% (0.4 mSv)
      for the head, 10% (0.8 and 1.4 mSv) for the chest and liver, 6% (0.8 mSv) for the
      abdomen and pelvis, and 4% (0.4 mSv) and 55% (1.0 mSv) for coronary CT
      angiography at pitches of 0.2 and 3.4. CONCLUSION: Use of dynamic z-axis
      collimation reduces dose in helical CT by minimizing overscanning. Percentage
      dose reductions are larger for shorter scan lengths and greater pitch values.

PMID- 20028891
TI  - Web-based teaching tool incorporating peer assessment and self-assessment:
      example of aligned teaching.
AB  - OBJECTIVE: Our objective was to create an electronic learning tool that
      incorporates the pedagogic advantages of peer assessment and self-assessment into
      report-generating skills. CONCLUSION: The tool was created using Web programming
      software. It was tested with 12 veterinary students and provided peer-peer and
      tutor-student interactions that supported learning. The tool is suited for
      training any professional concerned with the interpretation of images,
      particularly resident radiologists.

PMID- 20028892
TI  - Imaging of soft tissues adjacent to orthopedic hardware: comparison of 3-T and
      1.5-T MRI.
AB  - OBJECTIVE: The purpose of this study was to compare metal artifact reduction
      techniques at 1.5-T and 3-T MRI. MATERIALS AND METHODS: A titanium plate with
      steel screws was placed in a freshly harvested pig leg. The leg was imaged with
      1.5-T and 3-T MRI. A T2-weighted turbo spin-echo sequence was used with echo
      train lengths of 8, 16, 32, and 64 and a constant readout bandwidth of 31.2 kHz.
      The images were compared qualitatively, and the optimal echo-train length was
      selected. Images were acquired at the optimal echo-train length with four
      different readout bandwidths. Artifact was measured quantitatively, and image
      quality was ranked qualitatively. The qualitatively best image acquired at 1.5 T
      was compared with the qualitatively highest-ranked image acquired at 3 T.
      RESULTS: At both 1.5 T and 3 T, optimal images of equal quality were produced at
      echo-train lengths of 8 and 16. At higher readout bandwidths, there was
      quantitatively less artifact. The qualitatively best images were acquired at a
      readout bandwidth of 31.2 kHz at 1.5 T and 62.5 kHz at 3 T (Cronbach's
      alpha=1.00). The optimal image at 3 T was qualitatively superior to that at 1.5
      T. CONCLUSION: Optimizing image acquisition parameters in this phantom model
      resulted in similar quantitative susceptibility artifact at 3 T and 1.5 T and
      better qualitative images at 3 T than at 1.5 T.

PMID- 20028893
TI  - Evaluation of diffusion tensor imaging and fiber tractography of the median
      nerve: preliminary results on intrasubject variability and precision of
      measurements.
AB  - OBJECTIVE: The purposes of this study were to determine the intrasubject side-to
      side variability of quantitative and qualitative measures of diffusion tensor
      imaging (DTI) and fiber tractography of the median nerves and to determine the
      precision of quantitative measurements and fiber tractography. SUBJECTS AND
      METHODS: Fifteen healthy volunteers (seven men, eight women; mean age, 31.2
      years) underwent DTI of both wrists with a single-shot spin-echo-based echo
      planar imaging sequence (TR/TE, 7,000/103; b value 1,025 s/mm2). Postprocessing
      included fiber tractography and quantitative analysis of fiber length, fiber
      density index, fractional anisotropy, apparent diffusion coefficient, and signal
      to-noise ratio. Two readers in consensus graded the quality of fiber tract images
      of the two wrists as equal, slightly different, or very different. Fiber
      tractography and all analyses were repeated after 3 weeks, and the images from
      the two sessions were compared. RESULTS: No statistically significant side-to
      side differences in quantitative data were found (p=0.054-0.999). In all
      subjects, the quality of fiber tract images of the right and left median nerves
      was either slightly or very different. Between the initial and the second
      quantitative analyses, no statistically significant differences (p=0.086-0.898)
      were found, and the quality of fiber tract images was rated equal for nine of 15
      subjects (60%) and slightly different for six of 15 subjects (40%). CONCLUSION:
      Preliminary results indicate that quantitative evaluation of DTI of the median
      nerve is precise. The absence of statistically significant intrasubject side-to
      side variability in quantitative data suggests that the healthy contralateral
      nerve can be used as an internal control. Observed side-to-side variability in
      the quality of fiber tract images, however, rules out side-to-side comparisons in
      fiber tractography.

PMID- 20028894
TI  - Quantification of muscle choline concentrations by proton MR spectroscopy at 3 T:
      technical feasibility.
AB  - OBJECTIVE: The quantification of choline in musculoskeletal tissues has several
      potential uses, including characterizing malignancy, but has not been previously
      achievable. We present a method of measuring the absolute concentration of
      choline by proton MR spectroscopy (MRS) in skeletal muscle at 3 T. MATERIALS AND
      METHODS: At 3 T, choline measurements were performed in phantoms and healthy
      volunteers using proton MRS (point-resolved spectroscopy sequence [PRESS]; TR/TE,
      2,000/135). In vitro choline concentrations were measured in three phantom
      solutions (10, 5, 1.25 mmol). Choline T1 and T2 relaxation times were measured in
      the muscles of five healthy subjects. In vivo choline concentrations were
      measured using water as an internal reference and average T1 and T2 relaxation
      times in 20 muscle locations (quadriceps, hamstring, adductor) of seven healthy
      subjects (four men, three women). Descriptive statistics are reported. RESULTS:
      In vitro, the average measured choline concentrations of the 10-, 5-, and 1.25
      mmol solutions were 9.91, 5.03, and 1.22 mmol, respectively. In vivo, the average
      T1 and T2 relaxation times of choline were 1,372+/-57 (SD) and 134+/-11
      milliseconds, respectively. The average choline concentrations in the quadriceps
      and hamstring muscles were 10.0+/-0.4 (SD) and 8.0+/-2.9 mmol/kg. Interindividual
      variation existed in the choline concentrations (quadriceps range, 6.7-13
      mmol/kg), but there was little variation by patient sex. CONCLUSION: In the
      musculoskeletal system, the measurement of choline concentration by proton MRS at
      3 T is feasible using water as an internal reference. These data provide a
      quantitative basis for future investigations of metabolite concentrations in
      normal and diseased musculoskeletal tissues.

PMID- 20028895
TI  - Accessory head of biceps brachii muscle: anatomy, histology, and MRI in cadavers.
AB  - OBJECTIVE: The purpose of our study is to describe and define an anatomic
      variation located close to the bicipital groove using MRI with gross anatomic and
      histologic correlation in cadavers. MATERIALS AND METHODS: Ten fresh male human
      shoulders were harvested and used in this investigation. They were derived from
      persons with a mean age of death of 78.9 years (age range, 58-92 years). MR
      arthrography using proton density-weighted sequences was used to obtain images in
      axial, coronal, and sagittal planes. After imaging, the specimens were cut in
      axial, coronal, and sagittal sections using a band saw. The slices were then
      photographed to allow correlation with the MR arthrographic images, followed by
      histologic analysis. RESULTS: Two anomalous tendons, both intimate with the
      tendon of the long head of the biceps brachii muscle in the bicipital groove,
      were recognized. The origin of both tendons was in the greater tuberosity near
      the articular capsule. These structures had a muscular belly that was joined with
      the other biceps bellies. At the level of the bicipital groove, the anomalous
      tendons appeared as hypointense structures in proton density-weighted images,
      with a mostly flat morphology in axial and coronal planes. The average dimensions
      of these structures were 45.5 (craniocaudal)x6.2 (anteroposterior)x0.85
      (mediolateral) mm. CONCLUSION: The MR images, gross anatomic inspection, and
      histologic information led us to conclude that these anomalous structures were
      accessory heads of the biceps brachii muscle.

PMID- 20028896
TI  - Percutaneous radionuclide ablation of axial aneurysmal bone cysts.
AB  - OBJECTIVE: The purpose of our study was to retrospectively examine the efficacy
      of intralesional injection of 32P chromic phosphate, a beta-emitting colloidal
      radiopharmaceutical, in the treatment of aneurysmal bone cysts of the axial
      skeleton. Five patients with large aneurysmal bone cysts were managed with
      injection of 32P chromic phosphate into their tumors under CT guidance. With only
      a single minor complication, all lesions were observed to ossify on follow-up CT,
      with an average follow up of 2 years. CONCLUSION: CT-guided injection of axial
      aneurysmal bone cysts with 32P chromic phosphate leads to excellent local lesion
      control. In addition, the morbidity associated with this procedure is lower than
      that associated with surgical or other nonsurgical treatments.

PMID- 20028897
TI  - Clinical utility of PET/CT in lymphoma.
AB  - OBJECTIVE: The purpose of this review is to assist interpreting radiologists in
      becoming familiar with the role of PET/CT in baseline staging and therapeutic
      response assessment in the management of lymphoma, in becoming aware of imaging
      pitfalls, and in understanding the natural behavior of lymphoma and the
      therapeutic options. CONCLUSION: Therapeutic strategies for the management of
      lymphoma are constantly being refined to improve long-term survival with the
      lowest risk of toxicity to the patient. PET/CT is accurate for baseline staging
      and yields important prognostic information for determining the most appropriate
      initial treatment. Used for evaluation of treatment response, PET/CT can depict
      residual viable malignant lesions with greater accuracy than can other imaging
      techniques. The findings thereby influence decisions about the need for
      additional or alternative treatment.

PMID- 20028898
TI  - Evaluation of response in malignant tumors treated with the multitargeted
      tyrosine kinase inhibitor sorafenib: a multitechnique imaging assessment.
AB  - OBJECTIVE: The purpose of this article is to illustrate the characteristic
      changes induced in different tumor types by the multitargeted tyrosine kinase
      inhibitor sorafenib. CONCLUSION: Sorafenib reduces tumor perfusion and thereby
      induces necrosis and often hemorrhage. Malignant tumors treated with sorafenib
      undergo both morphologic and functional changes; however, the morphologic changes
      are less frequent and inadequate for early evaluation of response. Therefore,
      imaging tools accurately assessing hemorrhage and decrease in tumor perfusion
      with subsequent necrosis should be the mainstay in monitoring targeted therapy
      agents.

PMID- 20028899
TI  - Imaging of traumatic brain injury: a review of the recent medical literature.
AB  - OBJECTIVE: This article provides a summary of some of the important articles
      published during the period 2005-2009 on the topic of imaging findings in head
      trauma. The intent is to provide the latest information regarding the diagnosis
      of important abnormalities and new insights into their clinical significance.
      CONCLUSION: With the growing realization that even mild head injury can lead to
      various types of neurocognitive deficits, medical imaging of brain injury has
      assumed even greater importance than previously.

PMID- 20028900
TI  - Is progesterone worth consideration as a treatment for brain injury?

PMID- 20028901
TI  - Dual-energy CT angiography in the evaluation of intracranial aneurysms: image
      quality, radiation dose, and comparison with 3D rotational digital subtraction
      angiography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the image quality, radiation
      dose, and diagnostic accuracy of dual-energy CT angiography (CTA) compared with
      3D rotational digital subtraction angiography (DSA) in the detection of
      intracranial aneurysms. SUBJECTS AND METHODS: Forty-six patients with clinically
      suspected intracranial aneurysms underwent dual-source dual-energy CTA and 3D
      DSA. For the analysis of the image quality and radiation dose of dual-energy CTA,
      46 patients who underwent digital subtraction CTA were recruited as a control
      group. The image quality of dual-energy CTA and digital subtraction CTA was rated
      on a 4-point scale as excellent, good, moderate, or poor. The radiation dose of
      CTA was recorded according to patient protocol. Aneurysm detection with dual
      energy CTA compared with 3D DSA was analyzed on a per-patient and on a
      peraneurysm basis. Sensitivity, specificity, and positive and negative predictive
      values for aneurysm presence were determined. The mean maximum diameter and dome
      and neck dimensions of aneurysms were measured on dual-energy CTA and 3D DSA
      images. Correlation analysis between the two techniques was performed. RESULTS:
      There was no statistical difference between the image quality of dual-energy CTA
      and that of digital subtraction CTA (p>0.05). Patients undergoing dual-energy CTA
      received a smaller radiation dose (volume CT dose index, 20.6+/-0.1 mGy [mean+/
      SD]; dose-length product, 398.6+/-19.0 mGy x cm) than those undergoing digital
      subtraction CTA (volume CT dose index, 50.4+/-3.4 mGy; dose-length product,
      1,095.6+/-114.2 mGyxcm) (p<0.05). Three-dimensional DSA showed no aneurysm in 11
      patients and 40 aneurysms in 35 patients. The mean maximum diameter of the
      aneurysms was 6+/-3 mm; the dome measurement, 5+/-3 mm; and the neck dimension,
      3+/-2 mm. With dual-energy CTA, 38 aneurysms in 34 patients were correctly
      detected, and two aneurysms in two patients were missed. With DSA as the standard
      of reference, the sensitivity, specificity, and positive and negative predictive
      values of dual-energy CTA in the detection of intracranial aneurysm were 97.1%,
      100%, 100%, and 91.7% on a per-patient basis and 95.0%, 100%, 100%, and 99.7% on
      a per-aneurysm basis. Dual-energy CTA had sensitivities of 93.8%, 100%, and 80.0%
      and specificities of 100%, 100%, and 100% in the detection of aneurysms larger
      than 5 mm, those measuring 3.1-5 mm, and aneurysms 3 mm or smaller. At dual
      energy CTA, the mean maximum diameter and dome and neck dimensions were 6+/-3 mm,
      5+/-3 mm, and 3+/-2 mm. Excellent correlation was found between DSA and dual
      energy CTA findings with respect to mean maximum diameter and dome and neck
      dimensions (r=0.969, 0.957, and 0.870; p = 0.000). CONCLUSION: On the basis of
      the findings in the small series of patients evaluated, contrast-enhanced dual
      energy CTA had diagnostic image quality at a lower radiation dose than digital
      subtraction CTA and high diagnostic accuracy compared with 3D DSA in the
      detection of intracranial aneurysms.

PMID- 20028902
TI  - Biopsy of thyroid nodules: comparison of three sets of guidelines.
AB  - OBJECTIVE: The purpose of this study was to compare the results with three sets
      of guidelines for fine-needle aspiration biopsy of thyroid nodules. MATERIALS AND
      METHODS: A total of 1,398 nodules confirmed with fine-needle aspiration biopsy or
      surgery were included in the study. We compared the diagnostic value of three
      sets of guidelines for ultrasound findings that should lead to fine-needle
      aspiration biopsy of a nodule. According to the Kim criteria, a nodule should
      have at least one of the following findings: marked hypoechogenicity, irregular
      or microlobulated margins, microcalcifications, or length greater than width.
      According to the Society of Radiologists in Ultrasound, biopsy should be
      performed on a nodule 1 cm in diameter or larger with microcalcifications, 1.5 cm
      in diameter or larger that is solid or has coarse calcifications, and 2 cm in
      diameter or larger that has mixed solid and cystic components, and a nodule that
      has undergone substantial growth or is associated with abnormal cervical lymph
      nodes. According to the American Association of Clinical Endocrinologists, a
      hypoechoic nodule with at least one additional feature, such as irregular
      margins, length greater than width, and microcalcifications, should be biopsied.
      RESULTS: For all nodules, the diagnostic accuracy of the Kim (area under the
      receiver operating characteristic curve [Az]=0.868) and American Association of
      Clinical Endocrinologists (Az=0.850) criteria was greater than that of the
      Society of Radiologists in Ultrasound criteria (Az=0.551). The number of nodules
      for which fine-needle aspiration biopsy was recommended (25.6%) was smallest with
      use of the American Association of Clinical Endocrinologists criteria, and the
      smallest number (7.3%) of missed malignant lesions was associated with use of the
      Kim criteria. The results did not change for the subgroup with nodules larger
      than 1 cm. CONCLUSION: The Kim and American Association of Clinical
      Endocrinologists criteria are more accurate than the Society of Radiologists in
      Ultrasound criteria. The American Association of Clinical Endocrinologists
      guidelines are recommended for achieving high specificity, and the Kim criteria
      may be chosen for higher sensitivity.

PMID- 20028903
TI  - Diagnostic approach for evaluation of lymph node metastasis from thyroid cancer
      using ultrasound and fine-needle aspiration biopsy.
AB  - OBJECTIVE: The purpose of our study was to investigate ultrasound criteria to
      determine the most accurate criterion to differentiate metastatic from benign
      lymph nodes on ultrasound and to evaluate the frequency of metastasis according
      to the cytology results. MATERIALS AND METHODS: One hundred eighteen consecutive
      patients with thyroid malignancy underwent fine-needle biopsy of suspicious lymph
      nodes. We investigated the diagnostic performance of each ultrasound feature
      (loss of fatty hilum, presence of cystic change or calcification,
      hyperechogenicity, and round shape) and ultrasound criteria 1 and 2. We
      considered criterion 1 to be if one of the aforementioned malignant ultrasound
      findings was present and criterion 2 to be if one of the aforementioned malignant
      ultrasound findings, excluding the loss of fatty hilum, was present. Cytology
      results were divided into metastasis, macrophages without malignant cells, cell
      paucity, and negative for malignancy, and we evaluated the frequency of
      metastasis. RESULTS: There were 91 metastatic and 27 benign nodes. The area under
      the receiver operating characteristic curve value of criterion 2 was
      significantly higher than that of criterion 1. The frequency of metastasis was
      highest with a cytologic result of metastasis (95.8%), followed by macrophages
      without malignant cells (87.5%), cell paucity (71.4%), and negative for
      malignancy (34.4%). CONCLUSION: The most accurate ultrasound criterion to
      differentiate metastatic from benign lymph nodes was ultrasound criterion 2 (any
      suspicious ultrasound features except for loss of fatty hilum), and we should not
      neglect lymph nodes with suspicious ultrasound features, even if they do not
      contain malignant cells on cytology.

PMID- 20028904
TI  - Thyroid follicular carcinoma: sonographic features of 50 cases.
AB  - OBJECTIVE: The purpose of our study was to retrospectively evaluate sonography of
      thyroid follicular neoplasms for features that would aid in distinguishing
      follicular carcinoma from follicular adenoma and for any imaging features that
      distinguish the Hurthle-cell variant of follicular carcinoma from classic
      follicular carcinoma. MATERIALS AND METHODS: The study cohort consisted of
      patients with the diagnosis of follicular carcinoma and patients with the
      diagnosis of follicular adenoma. Fifty patients (25 men and 25 women; median age,
      59.5 years) with a diagnosis of follicular carcinoma (27 with classic follicular
      carcinoma, 22 with Hurthle-cell variant of follicular carcinoma, and one insular
      variant) in a 6-year period were included. Fifty-two control patients (10 men and
      42 women; median age, 46.5 years) were selected from a random sampling of all
      cases of follicular adenoma during the same time period. Sonograms were reviewed
      in consensus by four radiologists for various features. All study patients and
      control patients underwent surgical resection and pathologic analysis of their
      thyroid follicular neoplasm. The chi-square or Fisher's exact test was used for
      categorical variables; the Wilcoxon's rank sum test was used for continuous
      variables. RESULTS: Hypoechoic appearance (82% of follicular carcinoma patients
      vs 50% of follicular adenoma patients; p<0.005; odds ratio [OR]), 0.5; 95% CI,
      0.3-0.7), absence of halo (64% of follicular carcinoma patients vs 42% of
      follicular adenoma patients; p<0.05; OR, 0.4; 95% CI, 0.2-0.9), absence of cystic
      change (90% of follicular carcinoma patients vs 69% of follicular adenoma
      patients; p<0.05; OR, 0.2; 95% CI, 0.1-0.7), greater patient age (median age of
      59.5 years for follicular carcinoma patients vs 46.5 years for follicular adenoma
      patients; p<0.05), size of the tumor (median size of 11.75 mL for follicular
      carcinoma patients vs 5.95 mL for follicular adenoma patients; p<0.05), and male
      sex (50% of follicular carcinoma patients vs 19.2% of follicular adenoma
      patients; p<0.005; OR, 3.7; 95% CI, 1.6-8.9) were more frequently associated with
      follicular thyroid cancer than with benign adenoma. No significant difference in
      the prevalence of refractive shadowing, echotexture, visible invasion, lymph node
      enlargement, adjacent nonfollicular suspicious lesions, vascularity subtype, and
      calcifications was observed between the two groups. Within the follicular
      carcinoma subgroup, homogeneous or predominantly homogeneous echotexture (67% of
      classic follicular carcinoma patients vs 36% of Hurthle-cell variant of
      follicular carcinoma patients; p<0.05; OR, 3.5; 95% CI, 1.1-11.4) and the
      presence of calcifications (22% of classic follicular carcinoma patients vs 4% of
      Hurthle-cell variant of follicular carcinoma patients [multivariate analysis
      including age]; p < 0.05; OR, 22.9; 95% CI, 2.0-261.9) were associated with
      classic follicular carcinoma. Greater patient age (median age of 53 years for
      classic follicular carcinoma patients vs 64.5 years for Hurthle-cell variant of
      follicular carcinoma patients; p<0.05) was associated with Hurthle-cell variant
      follicular carcinoma. There was no association between tumor volume, sex,
      sonographic halo, refractive shadowing, echogenicity, visible invasion, lymph
      node enlargement, adjacent nonfollicular suspicious lesions, vascularity subtype,
      and cystic change between the subgroups of follicular carcinoma. CONCLUSION: The
      sonographic features of follicular adenoma and follicular carcinoma are very
      similar, but larger lesion size, lack of a sonographic halo, hypoechoic
      appearance, and absence of cystic change favored a follicular carcinoma
      diagnosis. Increased patient age and male sex are associated with malignancy.
      Within the follicular carcinoma subgroup, Hurthle-cell variant of follicular
      carcinoma is more often seen in older patients with nodules having a
      heterogeneous appearance and lacking internal calcifications.

PMID- 20028905
TI  - Accuracy of contrast-enhanced MDCT and MRI for identifying the severity and cause
      of neural foraminal stenosis in cervical radiculopathy: a prospective study.
AB  - OBJECTIVE: The purpose of this study was to determine the accuracy of IV contrast
      enhanced MDCT and MRI for evaluation of the severity and cause of neural
      foraminal stenosis in patients with cervical radiculopathy. SUBJECTS AND METHODS:
      Eighteen patients with cervical radiculopathy prospectively underwent contrast
      enhanced MDCT and MRI. Contrast-enhanced MDCT scans were acquired at 1-mm
      thickness and reconstructed in oblique axial (parallel to disk) and sagittal
      (perpendicular to neural foramen) 2-mm sections without a gap. The MRI sequences
      used were sagittal T1-weighted, fast spin-echo T2-weighted, 3D fast spin-echo T2
      weighted, axial T2-weighted, and 3D gradient-recalled echo. Three
      neuroradiologists independently and blindly rated the severity and cause of
      neural foraminal stenosis on a 4-point scale. Using the same scale at surgery,
      one of three surgeons rated the severity and cause of neural foraminal stenosis,
      and the results were used as the reference standard. Interobserver and
      intraobserver agreement (kappa) was calculated. RESULTS: For severity of neural
      foraminal stenosis, the sensitivities of contrast-enhanced MDCT (50/55, 91%) and
      MRI (55/57, 96%) were similar, as were their specificities (contrast-enhanced
      MDCT, 13/24, 54%; MRI, 11/24, 46%). For cause of neural foraminal stenosis, the
      accuracies of contrast-enhanced MDCT (46/54, 85%) and MRI (45/57, 79%) were
      similar. Interobserver agreement on severity of neural foraminal stenosis was
      moderate to almost perfect for contrast-enhanced MDCT (kappa=0.50-1.00) and MRI
      (kappa=0.43-1.00). For cause of neural foraminal stenosis, interobserver
      agreement was moderate to substantial for contrast-enhanced MDCT (kappa=0.52
      0.76) but only fair for MRI (kappa=0.23-0.39). Intra observer agreement was very
      high for severity of neural foraminal stenosis (contrast-enhanced MDCT,
      kappa=0.85; MRI, kappa=0.80) and cause of neural foraminal stenosis (contrast
      enhanced MDCT, kappa=0.86; MRI, kappa=1.00). CONCLUSION: Contrast-enhanced MDCT
      is as accurate as MRI in evaluation of the severity and cause of neural foraminal
      stenosis and may have better interobserver agreement.

PMID- 20028906
TI  - CT perfusion of head and neck tumors: how we do it.
AB  - OBJECTIVE: Our purpose is to illustrate the pathophysiologic, physical, and
      technical principles of MDCT perfusion imaging of head and neck tumors. The
      rationale for data acquisition and the interpretation of perfusion parameters
      will be discussed in the context of results recently published in the literature.
      CONCLUSION: MDCT perfusion imaging of primary and recurrent head and neck tumors
      is feasible and can yield functional information that is useful for tumor grading
      and assessment of treatment response.

PMID- 20028907
TI  - Clinical utility of multiplanar reformation in pulmonary CT angiography.
AB  - OBJECTIVE: The purpose of this study was to determine whether the view used,
      multiplanar or axial, for image interpretation at pulmonary CT angiography for
      suspected acute pulmonary embolism alters the diagnostic confidence, accuracy,
      and interpretation time of cardiothoracic radiology specialists and radiology
      residents. MATERIALS AND METHODS: Patients who underwent 50 consecutive pulmonary
      64-MDCT angiographic examinations formed the study group (18 men, 32 women; mean
      age, 53 years; range, 19-93 years). Three blinded cardiothoracic faculty
      radiologists and three blinded radiology residents reviewed each case
      independently initially using only axial display mode and later using multiplanar
      reformation (MPR) in any x-, y-, or z-axis. The presence of pulmonary embolism in
      the main through subsegmental pulmonary arteries was scored on a 5-point scale;
      diagnostic confidence for the overall examination was scored on a 3-point scale;
      and interpretation time was recorded. A surrogate reference standard consisted of
      either faculty agreement or, in cases of disagreement, adjudication by another,
      senior faculty member. Statistical analysis included the Kendall coefficient (W),
      receiver operating characteristics curves, and a univariate repeated measures
      model. RESULTS: Interobserver agreement between specialists on the diagnosis of
      pulmonary embolism was good for axial viewing (W=0.72) and for MPR viewing
      (W=0.79). Interobserver agreement between residents was good for axial viewing
      (W=0.62) and for MPR viewing (W=0.70). Reader confidence improved among all
      readers with MPR viewing, but the difference did not reach statistical
      significance. Interpretation time with MPR was significantly longer for two of
      the three specialists and significantly shorter for two of the three residents.
      CONCLUSION: Use of MPR for viewing increased the reader agreement and
      interpretation time of cardiothoracic specialists but increased reader agreement
      between residents and might have decreased interpretation time. All readers had a
      trend toward increased confidence.

PMID- 20028908
TI  - Pyothorax-associated lymphoma: imaging findings.
AB  - OBJECTIVE: The purpose of this study was to evaluate the radiologic features of
      pyothorax-associated lymphoma on CT scans and chest radiographs. MATERIALS AND
      METHODS: Radiographs and CT scans of 21 patients with biopsy-proven pyothorax
      associated lymphoma (17 men, four women; median age, 71 years; range 52-77 years)
      were retrospectively identified. Two readers in consensus analyzed the
      morphologic imaging features of pyothorax-associated lymphoma and determined
      their relation to the preexisting chronic empyema cavity. In 13 cases, gallium
      scans were available and were reviewed. RESULTS: Sixteen patients had a history
      of artificial pneumothorax therapy for tuberculosis. Pyothorax-associated
      lymphoma was visualized mainly (71.4% of cases) as extrapulmonary pleural masses
      on chest radiographs. The CT features included a lenticular (60%) or crescentic
      (20%) soft-tissue mass located eccentrically at the margin of a coexistent
      empyema cavity, which was present in all cases. Masses of pyothorax-associated
      lymphoma were commonly located in the lateral costal pleura (50%) or at the
      costophrenic angle (30%). The tumor matrix often appeared heterogeneous and
      contained areas of necrosis (60%). Direct invasion of the chest wall, ribs, lung
      parenchyma, and abdomen was found in 75%, 50%, 25%, and 25% of patients. Gallium
      scans, when available, showed marked uptake in 10 of 13 patients (76.9%).
      CONCLUSION: In patients who have undergone artificial pneumothorax therapy for
      tuberculosis more than 20 years in the past, a pleural soft-tissue mass adjacent
      to the margin of a coexistent empyema cavity suggests the presence of pyothorax
      associated lymphoma. Knowledge of the typical radiologic findings and locations
      of pyothorax-associated lymphoma help in the diagnosis of this rare pathologic
      entity.

PMID- 20028909
TI  - Assessment of in-stent restenosis using 64-MDCT: analysis of the CORE-64
      Multicenter International Trial.
AB  - OBJECTIVE: Evaluations of stents by MDCT from studies performed at single centers
      have yielded variable results with a high proportion of unassessable stents. The
      purpose of this study was to evaluate the accuracy of 64-MDCT angiography (MDCTA)
      in identifying in-stent restenosis in a multicenter trial. MATERIALS AND METHODS:
      The Coronary Evaluation Using Multidetector Spiral Computed Tomography
      Angiography Using 64 Detectors (CORE-64) Multicenter Trial and Registry evaluated
      the accuracy of 64-MDCTA in assessing 405 patients referred for coronary
      angiography. A total of 75 stents in 52 patients were assessed: 48 of 75 stents
      (64%) in 36 of 52 patients (69%) could be evaluated. The prevalence of in-stent
      restenosis by quantitative coronary angiography (QCA) in this subgroup was 23%
      (17/75). Eighty percent of the stents were <or=3.0 mm in diameter. RESULTS: The
      overall sensitivity, specificity, positive predictive value, and negative
      predictive value to detect 50% in-stent stenosis visually using MDCT compared
      with QCA was 33.3%, 91.7%, 57.1%, and 80.5%, respectively, with an overall
      accuracy of 77.1% for the 48 assessable stents. The ability to evaluate stents on
      MDCTA varied by stent type: Thick-strut stents such as Bx Velocity were
      assessable in 50% of the cases; Cypher, 62.5% of the cases; and thinner-strut
      stents such as Taxus, 75% of the cases. We performed quantitative assessment of
      in-stent contrast attenuation in Hounsfield units and correlated that value with
      the quantitative percentage of stenosis by QCA. The correlation coefficient
      between the average attenuation decrease and >or=50% stenosis by QCA was 0.25
      (p=0.073). Quantitative assessment failed to improve the accuracy of MDCT over
      qualitative assessment. CONCLUSION: The results of our study showed that 64-MDCT
      has poor ability to detect in-stent restenosis in small-diameter stents.
      Evaluability and negative predictive value were better in large-diameter stents.
      Thus, 64-MDCT may be appropriate for stent assessment in only selected patients.

PMID- 20028911
TI  - Lipoid pneumonia: spectrum of clinical and radiologic manifestations.
AB  - OBJECTIVE: Lipoid pneumonia results from accumulation of lipids in the alveoli
      and can be either exogenous or endogenous in cause based on the source of the
      lipid. Exogenous lipoid pneumonia is caused by inhalation or aspiration of animal
      fat or vegetable or mineral oil. Endogenous lipoid pneumonia is usually
      associated with bronchial obstruction. The purpose of this article is to review
      the pathogenesis and clinical and radiologic manifestations of exogenous and
      endogenous lipoid pneumonia. CONCLUSION: The ability to recognize the radiologic
      manifestations of lipoid pneumonia is important because, in the appropriate
      clinical setting, these findings can be diagnostic.

PMID- 20028910
TI  - Patient characteristics as predictors of image quality and diagnostic accuracy of
      MDCT compared with conventional coronary angiography for detecting coronary
      artery stenoses: CORE-64 Multicenter International Trial.
AB  - OBJECTIVE: The purpose of the study was to investigate patient characteristics
      associated with image quality and their impact on the diagnostic accuracy of MDCT
      for the detection of coronary artery stenosis. MATERIALS AND METHODS: Two hundred
      ninety-one patients with a coronary artery calcification (CAC) score of <or=600
      Agatston units (214 men and 77 women; mean age, 59.3+/-10.0 years [SD]) were
      analyzed. An overall image quality score was derived using an ordinal scale. The
      accuracy of quantitative MDCT to detect significant (>or=50%) stenoses was
      assessed using quantitative coronary angiography (QCA) per patient and per vessel
      using a modified 19-segment model. The effect of CAC, obesity, heart rate, and
      heart rate variability on image quality and accuracy were evaluated by multiple
      logistic regression. Image quality and accuracy were further analyzed in
      subgroups of significant predictor variables. Diagnostic analysis was determined
      for image quality strata using receiver operating characteristic (ROC) curves.
      RESULTS: Increasing body mass index (BMI) (odds ratio [OR]=0.89, p<0.001),
      increasing heart rate (OR=0.90, p<0.001), and the presence of breathing artifact
      (OR=4.97, p<or=0.001) were associated with poorer image quality whereas sex, CAC
      score, and heart rate variability were not. Compared with examinations of white
      patients, studies of black patients had significantly poorer image quality
      (OR=0.58, p=0.04). At a vessel level, CAC score (10 Agatston units) (OR=1.03,
      p=0.012) and patient age (OR=1.02, p=0.04) were significantly associated with the
      diagnostic accuracy of quantitative MDCT compared with QCA. A trend was observed
      in differences in the areas under the ROC curves across image quality strata at
      the vessel level (p=0.08). CONCLUSION: Image quality is significantly associated
      with patient ethnicity, BMI, mean scan heart rate, and the presence of breathing
      artifact but not with CAC score at a patient level. At a vessel level, CAC score
      and age were associated with reduced diagnostic accuracy.

PMID- 20028912
TI  - Role of 64-MDCT in evaluation of pulmonary atresia with ventricular septal
      defect.
AB  - OBJECTIVE: The purposes of this article are to describe the technical factors in
      performing 64-MDCT of pulmonary atresia with ventricular septal defect (PA-VSD),
      to describe the anatomic variations in pulmonary arterial circulation and other
      associated anomalies, and to describe the postoperative evaluation of this
      condition. CONCLUSION: The management of this complex condition has been largely
      determined by the morphology of pulmonary arteries and the extracardiac sources
      of pulmonary blood supply. Although echocardiography and catheter angiography are
      the traditional imaging techniques used to diagnose PA-VSD, 64-MDCT has become a
      valuable noninvasive imaging technique in comprehensive evaluation of this
      condition.

PMID- 20028913
TI  - Taxonomy and imaging spectrum of small bowel obstruction after Roux-en-Y gastric
      bypass surgery.
AB  - OBJECTIVE: For most patients with morbid obesity, bariatric surgery is the only
      effective method to achieve sustainable weight loss. Small bowel obstruction
      (SBO) after bariatric surgery is a major complication that affects postoperative
      course and management. Knowledge of the types of and imaging findings for SBO is
      essential to prompt diagnosis. CONCLUSION: We discuss different types of SBO and
      a taxonomic schemata of bowel obstruction (ABC classification) and present a
      review of imaging findings that facilitates optimal patient management.

PMID- 20028914
TI  - Utility of routine barium studies after adjustments of laparoscopically inserted
      gastric bands.
AB  - OBJECTIVE: The purposes of this study were to assess the utility of barium
      studies after adjustments of laparoscopically inserted gastric bands and to
      identify a threshold stomal diameter for predicting which bands should be
      loosened because of excessive tightening. MATERIALS AND METHODS: A total of 246
      patients with laparoscopically inserted adjustable gastric bands underwent 668
      routine band adjustments and barium studies after each adjustment. Forty-one
      barium studies of 30 patients with tight bands necessitating readjustment were
      compared with barium studies of 41 patients acting as controls. Barium studies of
      nine patients with obstructive symptoms before adjustment were reviewed to
      correlate stomal diameter with symptoms. The data were analyzed for a threshold
      stomal diameter below which obstructive symptoms were likely to develop. RESULTS:
      Mean stomal diameters were 2.9 mm for the group with tight bands after routine
      adjustment, 9.5 mm for the control group, and 5.1 mm for the group with
      obstructive symptoms. Thirty-nine of the 41 studies of tight bands after routine
      adjustment showed stomal diameters less than 6 mm. Seven of nine patients with
      obstructive symptoms and none of the 41 control patients had stomal diameters
      measuring less than 6 mm. Conversely, 40 of 41 control patients and two of nine
      patients with obstructive symptoms had stomal diameters greater than 6 mm. In
      none of the 41 cases in which the band was tight after routine adjustment was the
      stomal diameter greater than 6 mm. Thus, 6 mm was the threshold stomal diameter
      below which bands should be loosened. CONCLUSION: A stomal diameter of less than
      6 mm after routine adjustment of a laparoscopically inserted gastric band can
      cause obstructive symptoms, so the band should be loosened in these patients. In
      contrast, a stomal diameter greater than 7 mm is unlikely to cause obstructive
      symptoms, so band loosening usually is not required.

PMID- 20028915
TI  - CT findings of sigmoid volvulus.
AB  - OBJECTIVE: The purpose of this study was to evaluate the features of sigmoid
      volvulus on CT scanograms and cross-sectional images. MATERIALS AND METHODS: We
      retrospectively reviewed 21 cases of sigmoid volvulus in 15 men and six women.
      Three radiologists evaluated scanograms and cross-sectional images for several
      classic and two novel imaging signs of volvulus: crossing sigmoid transitions
      (called the X-marks-the-spot sign) and folding of the sigmoid wall by partial
      twisting (called the split-wall sign). A general impression was assigned to
      scanograms and cross-sectional images. CT findings suggesting bowel compromise
      were compared with pathologic and endoscopic findings. RESULTS: The most
      sensitive scanogram findings were absence of rectal gas (19 of 21 cases, 90%) and
      an inverted-U-shaped distended sigmoid (18 of 21 cases, 86%) followed by the
      coffee bean sign and disproportionate sigmoid enlargement (both 16 of 21 cases,
      76%). The most sensitive cross-sectional findings were one sigmoid colon
      transition point (20 of 21 cases, 95%) and disproportionate enlargement of the
      sigmoid (18 of 21 cases, 86%). The X-marks-the-spot and split-wall signs were
      present in nine of 21 (43%) and 11 of 21 (52%) patients, but one of the two signs
      was present in 18 of 21 patients (86%). Classic radiographic and definitive cross
      sectional findings were seen in 11 of 21 (52%) and 16 of 21 (76%) patients. CT
      findings were definitive in five of seven patients (71%) with indeterminate
      scanogram findings. Imaging signs suggesting bowel compromise correlated poorly
      with clinical ischemia, but CT features were present in all three patients with
      frank necrosis. CONCLUSION: Sigmoid volvulus has a spectrum of imaging findings.
      A classic appearance is absent on approximately one half of scanograms and one
      fourth of CT scans. Use of new signs that model the pathophysiologic
      characteristics of volvulus (X-marks-the-spot sign for more complete twisting and
      split-wall sign for less severe twisting) may improve diagnostic confidence.

PMID- 20028916
TI  - Combined vascular-excretory phase MDCT angiography in the preoperative evaluation
      of renal donors.
AB  - OBJECTIVE: The objective of our study was to test a dose reduction protocol that
      uses combined vascular-excretory phase scanning achieved by split IV contrast
      injection and compare it with conventional multiphase MDCT angiography (MDCTA) in
      evaluating potential renal donors. MATERIALS AND METHODS: This study is a review
      of MDCTA examinations of 54 potential renal donors scanned on 16- and 64-MDCT.
      The IV bolus was split: 50 mL was administered 3 minutes before scanning and a
      second injection of 70-100 mL was administered at a rate of 4-6 mL/s, with CT
      angiography started by bolus tracking. The second vascular (venous) phase was
      acquired 20 seconds later. Two readers reviewed the two phases, assessed vascular
      and parenchymal anatomy and variants or abnormalities, graded the added value of
      the venous phase on a 5-point scale, and took attenuation measurements in
      Hounsfield units. The operative notes of 39 subjects were reviewed as the
      reference standard for anatomic findings and compared with CT reports. RESULTS:
      All of the relevant anatomy findings, according to the operative notes, were
      accurately depicted by MDCTA, and all were well recognized on the arterial phase.
      The arterial phase combined information from the arterial, venous, parenchymal,
      and excretory phases. The venous phase was inferior to the arterial phase in
      assessing the renal arteries without additional venous, parenchymal, or excretory
      phase information. The mean renal artery attenuation was 355 HU in the first
      phase versus 173 HU in the second phase (p<0.0001). The mean renal vein
      attenuation was not significantly different between the two phases. The
      parenchymal system and excretory system were equally well depicted in both
      vascular phases. CONCLUSION: Split-bolus contrast injection and combined vascular
      excretory phase scanning are adequate for studying potential renal donors and
      result in a marked decrease in multiphase scanning and, thus, in radiation dose.

PMID- 20028917
TI  - Bladder tumor staging: comparison of contrast-enhanced and gray-scale ultrasound.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      contrast-enhanced sonography in comparison with conventional sonography in
      differentiating muscle-infiltrating and superficial neoplasms of the urinary
      bladder. SUBJECTS AND METHODS: Conventional and contrast-enhanced sonography were
      performed on 34 consecutively registered patients with bladder tumors. All
      examinations were reviewed by two independent sonologists. At gray-scale
      sonography, interruption of the hyperechoic bladder wall was considered the main
      diagnostic criterion for differentiating superficial and infiltrating tumors. At
      contrast-enhanced sonography, a tumor was considered superficial when the
      hypoenhancing muscle layer of the bladder wall was intact; disruption of the
      muscle layer by enhancing tumor tissue was considered diagnostic of infiltration.
      A level of confidence in the diagnosis of tumor infiltration of the muscle layer
      was assigned on a 5-degree scale. Receiver operating characteristic analysis was
      used to assess overall confidence in the diagnosis of muscle infiltration by
      tumor at both conventional and contrast-enhanced sonography. Histologic diagnosis
      was obtained for all patients. RESULTS: Final pathologic staging revealed 25
      superficial tumors (Ta-T1 disease) and nine muscle-infiltrating tumors (>T1).
      Conventional sonography depicted five of nine muscle-infiltrating tumors, and
      contrast-enhanced sonography depicted all nine. The diagnostic performance of
      contrast-enhanced sonography approached that of the reference standard (area
      under the receiver operating characteristic curve, 0.996), but the diagnostic
      performance of gray-scale ultrasound was worse (area under curve, 0.613).
      CONCLUSION: Our study showed that contrast-enhanced sonography is better than
      conventional sonography for differentiating muscle-infiltrating and superficial
      neoplasms of the urinary bladder.

PMID- 20028918
TI  - Assessing tumor response and detecting recurrence in metastatic renal cell
      carcinoma on targeted therapy: importance of size and attenuation on contrast
      enhanced CT.
AB  - OBJECTIVE: The aim of this study was to improve response assessment in patients
      with metastatic renal cell carcinoma (RCC) on antiangiogenic targeted therapy by
      evaluating changes in both tumor size and attenuation and by detecting unique
      patterns of contrast enhancement on contrast-enhanced CT (CECT). MATERIALS AND
      METHODS: Tumor long-axis measurements and volumetric mean tumor attenuation of
      target lesions on CECT images were correlated with time to progression in 53
      patients with metastatic clear cell RCC treated with first-line sorafenib or
      sunitinib. The frequencies of specific patterns of tumor progression were
      assessed. The data were used to develop new imaging criteria, the size and
      attenuation CT (SACT) criteria. CECT findings were evaluated using the SACT
      criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and modified
      Choi criteria, and the Kaplan-Meier method was used to estimate survival
      functions. RESULTS: One or more target metastatic lesions had decreased
      attenuation of >or=40 HU in 59% of patients with progression-free survival of
      >250 days (n=44) after initiating targeted therapy; 0% of patients with earlier
      disease progression (n=9) had this finding. A favorable response based on SACT
      criteria had a sensitivity of 75% and specificity of 100% for identifying
      patients with progression-free survival of >250 days, versus 16% and 100%,
      respectively, for RECIST and 93% and 44% for the modified Choi criteria.
      CONCLUSION: Objectively measuring changes in both tumor size and attenuation on
      the first CECT study after initiating targeted therapy for metastatic RCC
      markedly improves response assessment. Distinct patterns of disease recurrence
      are seen in patients with metastatic RCC on targeted therapy.

PMID- 20028920
TI  - Masters of radiology panel discussion: responding to health care reform and other
      market pressures.

PMID- 20028919
TI  - Perfusion CT in patients with metastatic renal cell carcinoma treated with
      interferon.
AB  - OBJECTIVE: The objective of our study was to assess the potential value of tumor
      perfusion parameters measured by perfusion CT as possible biomarkers of prognosis
      and early indicator of treatment efficacy in patients with metastatic
      conventional renal cell carcinoma (RCC) treated with interferon. MATERIALS AND
      METHODS: This study comprised 37 patients with metastatic RCC who were enrolled
      in a larger (n=118) randomized clinical trial of intermediate- versus low-dose
      interferon. Tumor perfusion parameters-that is, tumor blood flow, blood volume,
      mean transit time (MTT), and permeability-surface area product-of index
      metastatic lesions were obtained at baseline and at 8-week follow-up. Baseline
      perfusion parameters and changes at follow-up were compared, and their
      associations with patient progression-free survival were estimated. Univariate
      and multivariate analyses were performed. RESULTS: Twenty-eight patients were
      assessable. Median progression-free survival was 5.3 months (95% CI, 2.4-7.4
      months), with one partial response. Tumor blood flow at baseline was inversely
      associated with patient progression-free survival in both univariate (hazard
      ratio [HR]=1.006, p=0.025) and multivariate (HR=1.007, p=0.012) analyses. There
      were significant increases in tumor blood flow and reductions in MTT on follow-up
      scans compared with baseline scans (both, p=0.04), but no association between
      changes in perfusion parameters and progression-free survival was detected.
      CONCLUSION: Patients with highly vascularized metastatic RCC as shown by high
      baseline tumor blood flow appear to have a worse prognosis than those who do not.
      Tumor perfusion may be a useful biomarker of prognosis and additionally, in the
      future, may assist in treatment stratification. The potential utility of
      perfusion CT as an early response indicator was probably inadequately assessed in
      this study because of the limited antiangiogenic activity of interferon in
      metastatic RCC.

PMID- 20028921
TI  - Demographic changes in radiology residency positions 1980-2007: the divergence
      between California and the rest of the United States.
AB  - OBJECTIVE: The objective of our study was to show the disparity in the expansion
      of radiology residency training slots over the past 27 years between California
      and the rest of the United States and to relate that divergent distribution to
      regional differences in medical school enrollment as a precursor and state-based
      per capita ratios of population to radiologist trainees as a consequence.
      MATERIALS AND METHODS: Radiology positions were obtained from the annual editions
      of the American Medical Association's Graduate Medical Educational Directory.
      Population data were recorded from U.S. censuses for 1980, 1990, 2000, and 2007.
      Medical school matriculant data were provided by the American Association of
      Medical Colleges. The numbers of radiologists in practice were provided by the
      American College of Radiology. RESULTS: From 1980 to 2007, the U.S. population
      increased by 35%, predominantly in the South (52%) and West (65%). At the same
      time, the number of medical school matriculants remained relatively constant.
      Simultaneously diagnostic radiology positions increased by 55%, rising from 1980
      to 1993, declining until 2001, and rising again since then. The greatest
      increases in radiology residency positions were observed in the Northeast and
      South, and the least increase was seen in the West. The greatest discrepancy
      between concomitant population growth and radiology resident positions occurred
      in California where training slots increased by 17% while population grew by 54%.
      CONCLUSION: Since 1980, a disparity between population growth and radiology
      residency position growth has been sustained between the West and the rest of the
      country. This disparity is a consequence of California's policy of restricting
      medical school enrollment and radiology residency positions despite continual
      population growth.

PMID- 20028922
TI  - Radiation dose from cone beam CT in a pediatric phantom: risk estimation of
      cancer incidence.
AB  - OBJECTIVE: The objective of our study was to measure absorbed doses and calculate
      effective dose (ED) from cone beam CT (CBCT) with metal oxide semiconductor field
      effect transistor (MOSFET) detectors in an anthropomorphic phantom and to
      estimate the risk of cancer incidence for CBCT. MATERIALS AND METHODS: Abdominal
      CBCT was performed in an anthropomorphic phantom of a 5-year-old child using the
      On-Board Imager with arbitrarily designated standard-dose (125 kVp, 80 mA, 25
      milliseconds) and low-dose (125 kVp, 40 mA, 10 milliseconds) modes. The full-fan
      mode was used, and 20 MOSFET dosimeters were used to measure the absorbed doses
      in various organs. We calculated the ED, the lifetime attributable risk (LAR) for
      cancer incidence, and relative risk (RR) of cancer induction from a single scan
      for both standard- and low-dose modes in 5-year-old children. RESULTS: The
      highest absorbed doses were found in the skin, ascending colon, and stomach. The
      mean ED was 37.8+/-0.7 (SD) mSv for the standard-dose mode and 8.1+/-0.2 mSv for
      the low-dose mode. The LAR of cancer incidence ranged from 23 to 144 cases per
      100,000 exposed persons for the standard-dose mode and from five to 31 cases per
      100,000 exposed persons for the low-dose mode. The RR of cancer incidence ranged
      from 1.003 to 1.054 for the standard-dose mode and from 1.001 to 1.012 for the
      low-dose mode. CONCLUSION: The ED from pediatric CBCT using the standard-dose
      mode was considerably higher than that of MDCT, whereas the ED for CBCT using the
      low-dose mode was comparable to that of abdominal MDCT. For abdominal CBCT in the
      pediatric phantom, the highest LARs were for colon and bladder cancers and the
      highest RRs were for stomach and liver cancers.

PMID- 20028923
TI  - Innovations in CT dose reduction strategy: application of the adaptive
      statistical iterative reconstruction algorithm.
AB  - OBJECTIVE: The purpose of this article is to discuss the application of a new CT
      reconstruction algorithm, adaptive statistical iterative reconstruction (ASIR),
      to reduce radiation dose at body CT and to provide imaging examples in comparison
      with low-dose and standard-dose filtered back projection CT. CONCLUSION: The ASIR
      reconstruction algorithm is a promising technique for providing diagnostic
      quality CT images at significantly reduced radiation doses.

PMID- 20028924
TI  - Effectiveness of ultrasound-guided corticosteroid injection for the treatment of
      gluteus medius tendinopathy.
AB  - OBJECTIVE: The objective of our study was to evaluate the effectiveness of
      ultrasound-guided corticosteroid injection for the treatment of gluteus medius
      tendinopathy. SUBJECTS AND METHODS: We prospectively evaluated 54 consecutive
      patients (48 women, six men; mean age, 54.7 years; mean body mass index, 26
      kg/m2) with a clinical diagnosis of gluteus medius tendinopathy. Pain assessment
      using a 10-cm visual analog scale (VAS) was obtained as part of the initial
      clinical evaluation of all patients. A hip ultrasound study was performed
      followed by a gluteus medius peritendinous ultrasound-guided injection of 30 mg
      of triamcinolone combined with 3 mL of bupivacaine 0.5% using an anterior oblique
      coronal plane. One month after treatment, participants were reassessed
      clinically, and they were asked to quantify their pain using the VAS pain score
      and their satisfaction with the outcome of the injection using a 4-point rating
      scale (very satisfied, somewhat satisfied, somewhat dissatisfied, or very
      dissatisfied). Statistical analysis included a paired Student's t test
      (comparison of pain levels before and after treatment, p=0.05) and a multivariate
      analysis of covariance. RESULTS: There was a 55% average reduction of pain level
      before versus after treatment (mean VAS pain score, 6.4 vs 2.9 cm, respectively;
      p<0.001). One month after treatment, 72% of the patients showed a clinically
      significant improvement in pain level, which was defined as a reduction in the
      VAS pain score of >or=30%. Seventy percent of patients were satisfied with the
      results of the intervention. No correlation was shown between treatment outcome
      and any of the clinical variables or ultrasound findings. CONCLUSION: Our study
      shows that a peritendinous ultrasound-guided corticosteroid injection may be an
      effective treatment of gluteus medius tendinopathy.

PMID- 20028925
TI  - Unilateral lumbar spondylolysis on radiography and MRI: emphasis on morphologic
      differences according to involved segment.
AB  - OBJECTIVE: The objective of our study was to retrospectively compare the
      radiography and MRI findings of unilateral spondylolysis in the upper lumbar
      segment and in the lower lumbar segment and to consider how these radiologic
      findings can be applied in the diagnosis of unilateral spondylolysis. MATERIALS
      AND METHODS: Thirty patients with unilateral lumbar spondylolysis were
      categorized into one of two groups according to the lumbar levels involved with
      pars interarticularis defects: group A (L1, L2, and L3) or group B (L4 and L5).
      On radiographs, we evaluated contour bulging of the affected pars
      interarticularis, reactive sclerosis in the contralateral pedicle,
      anterolisthesis of the involved vertebra, and deviation of the spinous process.
      On MRI, we assessed pseudoarticulation of the pars interarticularis defect,
      uneven distribution of posterior epidural fat, the interspinous distance between
      adjacent segments, facet and disk degeneration in adjacent segments, and other
      anomalous changes. RESULTS: Among the 63 patients with unilateral spondylolysis,
      the upper lumbar segment was involved in 29 and the lower lumbar segment, in 34.
      Group A often displayed contour bulging of the affected pars interarticularis,
      reactive sclerosis of the contralateral pedicle, and contralateral deviation of
      the spinous process, all of which were easily detectable on radiography. Group B
      frequently showed anterolisthesis, pseudoarticulation of the pars
      interarticularis defect, adjacent facet-disk degeneration, and other anomalous
      changes that were well observed on MRI. CONCLUSION: Unilateral lumbar
      spondylolysis displayed radiologic differences in morphology of the isthmic
      defect itself and in ancillary findings of the adjacent structures based on the
      segment involved. Recognition of different ancillary features of unilateral
      spondylolysis with the use of a feasible diagnostic tool can be helpful for the
      diagnosis of cases in which a direct sign of isthmic defect is equivocal.

PMID- 20028926
TI  - Musculoskeletal sonography: important imaging pitfalls.
AB  - OBJECTIVE: The purpose of this article is to describe the pitfalls that may be
      encountered when performing musculoskeletal sonography. CONCLUSION: Sonography of
      the musculoskeletal system is a useful diagnostic technique, but awareness and
      understanding of the pitfalls will minimize errors in diagnosis.

PMID- 20028927
TI  - FDG PET/CT in assessment of pulmonary lymphangitic carcinomatosis.
AB  - OBJECTIVE: The purpose of this study was to assess the role of PET/CT in the
      diagnosis of pulmonary lymphangitic carcinomatosis. MATERIALS AND METHODS:
      Integrated PET/CT images of 35 patients (15 men, 20 women; mean age, 64.5 years)
      with pulmonary lymphangitic carcinomatosis confirmed at follow-up chest CT or
      histopathologic examination were analyzed retrospectively. Standardized uptake
      value based on body weight and the initial injected activity was measured in the
      affected lung, the normal lung, and the mediastinal blood pool. Two radiologists
      independently assessed abnormal PET activity in the lungs. Both radiologists
      reviewed the CT images to determine the presence, size, location, and extent of
      pulmonary lymphangitic carcinomatosis. The data were analyzed to determine the
      sensitivity and specificity of PET for pulmonary lymphangitic carcinomatosis.
      RESULTS: Among the 35 patients with pulmonary lymphangitic carcinomatosis, 17
      (49%), 13 (37%), and five (14%) patients had diffuse, focal, and bilateral
      pulmonary lymphangitic carcinomatosis, respectively. Thirty of the 35 patients
      had nodular septal thickening as the chief CT finding of pulmonary lymphangitic
      carcinomatosis. Subjective assessment showed a visually identifiable increase in
      uptake in the region of pulmonary lymphangitic carcinomatosis in 30 of the 35
      patients (86%). Four of the other five patients had focal pulmonary lymphangitic
      carcinomatosis, and one patient had diffuse pulmonary lymphangitic carcinomatosis
      of the right lung. The specificity of PET/CT for pulmonary lymphangitic
      carcinomatosis was 100%, and the sensitivity was 86%. The mean standardized
      uptake value in the region of pulmonary lymphangitic carcinomatosis (1.37+/-0.64)
      was significantly greater than that in normal lung (0.51+/-0.29) (p<0.0001). The
      standardized uptake ratio of mediastinal blood pool to lymphangitic lung was
      1.26+/-0.45, and that of blood pool to normal lung was 3.78+/-1.37. CONCLUSION:
      FDG PET/CT has high specificity in the detection of pulmonary lymphangitic
      carcinomatosis. Focal pulmonary lymphangitic carcinomatosis close to a primary
      malignant tumor, however, can be missed at PET.

PMID- 20028928
TI  - Neuroendocrine cell hyperplasia of infancy: diagnosis with high-resolution CT.
AB  - OBJECTIVE: Neuroendocrine cell hyperplasia of infancy is a form of childhood
      interstitial lung disease originally reported as persistent tachypnea of infancy.
      Reports of small series of cases and anecdotal experience have suggested that
      this disorder may have a consistent CT pattern. The purpose of this study was to
      review the CT findings in children with neuroendocrine cell hyperplasia of
      infancy to determine the findings at high-resolution CT, the diagnostic accuracy
      of CT compared with biopsy, and interrater reliability. MATERIALS AND METHODS:
      Images from 23 CT examinations of children with biopsy-proven neuroendocrine cell
      hyperplasia of infancy and six CT examinations of children with other childhood
      interstitial lung diseases were reviewed by two pediatric radiologists with
      special expertise in thoracic imaging. Identifying digital data were removed, and
      images were reviewed without clinical data. A CT assessment form was completed
      for each patient. RESULTS: Ground-glass opacification was the most common finding
      in patients with neuroendocrine cell hyperplasia of infancy. The right middle
      lobe and lingula were most commonly involved. Air trapping with a mosaic pattern
      was the second most common finding. Interrater reliability was very good with a
      kappa value of 0.93. The sensitivity and specificity of CT in the diagnosis of
      neuroendocrine cell hyperplasia of infancy were at least 78% and 100%.
      CONCLUSION: Neuroendocrine cell hyperplasia of infancy can have a characteristic
      appearance on high-resolution CT scans, the imaging findings being useful in
      differentiating neuroendocrine cell hyperplasia of infancy from other types of
      childhood interstitial lung disease. The appearance aids radiologists in
      suggesting a specific diagnosis but does not exclude this diagnosis; in 17-22% of
      cases, the readers in this study did not suggest the diagnosis of neuroendocrine
      cell hyperplasia of infancy when it was present.

PMID- 20028930
TI  - MRI of surgical repair of transposition of the great vessels.
AB  - OBJECTIVE: Our objectives are to review the surgical procedures that have been
      performed for the treatment of transposition of the great vessels. Using MRI, we
      illustrate the normal postoperative findings and many of the long-term
      complications for each of the surgical procedures. CONCLUSION: MRI is an
      extremely useful imaging method for evaluation of normal and abnormal findings
      after surgical repair of transposition of the aorta and pulmonary artery.

PMID- 20028929
TI  - Estimation of potential excess cancer incidence in pediatric 201Tl imaging.
AB  - OBJECTIVE: Little information is available regarding doses of ionizing radiation
      from medical imaging in the growing population of children undergoing therapy for
      cancer who are at risk of developing second cancers. The purpose of our study was
      to estimate the potential excess lifetime cancer incidence and mortality
      associated with thallium bone imaging in pediatric patients. MATERIALS AND
      METHODS: We retrospectively reviewed the medical records of pediatric patients
      treated between August 1991 and December 2003 for newly diagnosed osteosarcoma
      who underwent 201Tl imaging as part of the treatment protocol. According to age
      at diagnosis and doses of 201Tl, we estimated the excess cancer incidence and
      cancer mortality for boys and girls at 5 and 15 years old. RESULTS: The study
      cohort consisted of 73 patients, 32 males (median age at diagnosis, 14.8 years;
      age range, 8.1-20.1 years) and 41 females (median age at diagnosis, 13.3 years;
      age range, 6.0-20.7 years). Patients underwent a total of three 201Tl studies
      with a median dose of 4.4 mCi (162.8 MBq) (range, 2.2-8.4 mCi [81.4-310.8 MBq])
      per study. Total median cumulative patient radiation dose for 201Tl studies was
      18.6 rem (186 mSv) (range, 8.4-44.2 rem [84-442 mSv]) for males and 21.5 rem (215
      mSv) (range, 7.0-43.8 rem [70-438 mSv]) for females. Estimated excess cancer
      incidence was 6.0 per 100 (male) and 13.0 per 100 (female) if exposed by 5 years
      of age; 2.0 per 100 (male) and 3.1 per 100 (female) by 15 years of age. Estimated
      excess cancer mortality was 3.0 per 100 for males and 5.2 per 100 for females at
      5 years of age; 1.0 per 100 (male) and 1.4 per 100 (female) exposed at 15 years
      of age. CONCLUSION: Further reduction of doses in younger patients is needed to
      consider 201Tl a viable option for imaging osteosarcoma.

PMID- 20028931
TI  - Early infectious complications of percutaneous metallic stent insertion for
      malignant biliary obstruction.
AB  - OBJECTIVE: This study was designed to evaluate predisposing factors for early
      infectious complications after percutaneous metallic biliary stent insertion in
      patients with malignant biliary obstruction. MATERIALS AND METHODS: From August
      1999 to June 2008, 215 consecutively registered patients with inoperable
      malignant biliary obstruction were treated with percutaneous placement of a
      metallic stent. The incidence of early infectious complications was evaluated.
      Sex, age, level of obstruction, type and number of stents, and stent position
      (across or above the main duodenal papilla) were retrospectively reviewed. The
      findings in patients with early infectious complications were compared with those
      in patients without early infectious complications. RESULTS: Infectious
      complications occurred within 30 days after stent placement in 14 of 215 (6.5%)
      patients. Univariate analysis showed a significant difference between the two
      groups with respect to nontranspapillary stent placement (p=0.003). In the
      multiple logistic regression analysis, age, sex, level of obstruction, and type
      and number of stents were negatively associated with the development of early
      infectious complications (p>0.05). CONCLUSION: Our study data showed that stent
      placement across the main duodenal papilla seemed to prevent early infectious
      complications after percutaneous metallic biliary stent insertion in patients
      with malignant biliary obstruction.

PMID- 20028932
TI  - Core needle lung biopsy specimens: adequacy for EGFR and KRAS mutational
      analysis.
AB  - OBJECTIVE: The purpose of this study was to prospectively compare the adequacy of
      core needle biopsy specimens with the adequacy of specimens from resected tissue,
      the histologic reference standard, for mutational analysis of malignant tumors of
      the lung. SUBJECTS AND METHODS: The first 18 patients enrolled in a phase 2 study
      of gefitinib for lung cancer in July 2004 through August 2005 underwent CT- or
      fluoroscopy-guided lung biopsy before the start of gefitinib therapy. Three weeks
      after gefitinib therapy, the patients underwent lung tumor resection. The results
      of EGFR and KRAS mutational analysis of the core needle biopsy specimens were
      compared with those of EGFR and KRAS mutational analysis of the surgical
      specimens. RESULTS: Two specimens were unsatisfactory for mutational analysis.
      The results of mutational assay results of the other 16 specimens were the same
      as those of analysis of the surgical specimens obtained an average of 31 days
      after biopsy. CONCLUSION: Biopsy with small (18- to 20-gauge) core needles can
      yield sufficient and reliable samples for mutational analysis. This technique is
      likely to become an important tool with the increasing use of pharmacotherapy
      based on the genetics of specific tumors in individual patients.

PMID- 20028933
TI  - Leiomyoma shrinkage after MRI-guided focused ultrasound treatment: report of 80
      patients.
AB  - OBJECTIVE: The purpose of this study was to assess the degree of leiomyoma
      ablation and shrinkage after MRI-guided focused ultrasound treatment performed
      according to U.S. Food and Drug Administration protocols for commercial trials.
      MATERIALS AND METHODS: A total of 147 symptomatic leiomyomas in 80 women (average
      age, 46 years; range, 34-55 years) were managed with MRI-guided focused
      ultrasound. The average volume of treated fibroids was 175+/-201 (SD) cm3. Before
      treatment, T2-weighted MR images in three planes were obtained to measure
      leiomyoma volume. Immediately after treatment, T1-weighted contrast-enhanced fat
      suppressed MR images in three planes were used to measure nonperfused volume
      ratio. Similar images obtained 6 months after treatment were used to determine
      leiomyoma shrinkage. Qualitative and quantitative relations between fibroid
      volume, nonperfused volume ratio at treatment, and 6-month shrinkage were
      measured. RESULTS: The average nonperfused volume ratio was 55%+/-25% immediately
      after treatment. Six months after treatment, the average volume of treated
      fibroids had decreased to 112+/-141 cm3 (n=81) (p<0.0001) with an average volume
      reduction of 31%+/-28%. A linear regression model showed highly significant
      correlation between posttreatment nonperfused volume ratio and shrinkage at 6
      months (p<0.0001). CONCLUSION: MRI-guided focused ultrasound therapy for
      leiomyoma can result in nonperfused volume ratio and shrinkage that exceed those
      in previous clinical trials because the treatment guidelines have been relaxed to
      allow a greater amount of tissue ablation. The results suggest that a larger
      nonperfused volume ratio can be achieved, resulting in greater shrinkage and
      improved relief of symptoms.

PMID- 20028934
TI  - Interaction between SNPs in the NRF2 gene and elite endurance performance.
AB  - Nuclear respiratory factor 2 (NRF2), a member of the Cap-N-Collar family of
      transcription factors, plays an important role in the mitochondrial biogenesis,
      and variants of NRF2 gene have been associated with endurance performance. The
      aims of the present study were 1) to compare NRF2 A/C (rs12594956) and NRF2 C/T
      (rs8031031) genotype and allele frequencies between athletes of sports with
      different demands (endurance vs. sprinters) as well as between competitive levels
      (elite level vs. national level) and 2) to analyze the interaction of these two
      polymorphisms and its influence on the level of endurance performance. One
      hundred and fifty-five track and field athletes (74 endurance athletes and 81
      sprinters) and 240 nonathletic healthy individuals participated in this study.
      Endurance athletes presented a higher frequency of the AA (rs12594956) and CT
      (rs8031031) genotypes than sprinters and the control group, as well as higher A
      and T alleles, respectively. These differences did not appear between the
      sprinters and control subjects. The odds ratio for harboring the "optimal
      genotype" (NRF2 AA+ NRF2 CT) was 4.53 (95% confidence interval 1.23-16.6) in the
      whole cohort of endurance athletes and 6.55 (95% confidence interval 1.12-38.25)
      in elite-level endurance athletes, compared with control subjects and both levels
      of sprinters. In conclusion, our data indicate that the NRF2 A/C and NRF2 C/T
      single nucleotide polymorphisms (SNPs) are associated, separately and in
      combination, with elite endurance athletes, which supports the notion that these
      specific gene variants might belong to a growing group of SNPs that are
      associated with endurance performance.

PMID- 20028935
TI  - EDNRA variants associate with smooth muscle mRNA levels, cell proliferation
      rates, and cystic fibrosis pulmonary disease severity.
AB  - Airway inflammation and pulmonary disease are heterogeneous phenotypes in cystic
      fibrosis (CF) patients, even among patients with the same cystic fibrosis
      transmembrane conductance regulator (CFTR) genotype. Endothelin, a
      proinflammatory peptide and smooth muscle agonist, is increased in CF airways,
      potentially contributing to the pulmonary phenotype. Four cohorts of CF patients
      were screened for variants in endothelin pathway genes to determine whether any
      of these variants associated with pulmonary function. An initial cohort of 808 CF
      patients homozygous for the common CF mutation, DeltaF508, showed significant
      association for polymorphisms in the endothelin receptor A gene, EDNRA (P =
      0.04), but not in the related endothelin genes (EDN1, EDN2, EDN3, or EDNRB) or
      NOS1, NOS2A, or NOS3. Variants within EDNRA were examined in three additional
      cohorts of CF patients, 238 patients from Seattle, WA, 303 from Ireland and the
      U.K., and 228 from Cleveland, OH, for a total of 1,577 CF patients. The three
      additional groups each demonstrated a significant association between EDNRA 3'
      untranslated region (UTR) variant rs5335 and pulmonary function (P = 0.002). At
      the molecular level, single nucleotide primer extension assays suggest that the
      effect of the variants is quantitative. EDNRA mRNA levels from cultured primary
      tracheal smooth muscle cells are greater for the allele that appears to be
      deleterious to lung function than for the protective allele, suggesting a
      mechanism by which increased receptor function is harmful to the CF airway.
      Finally, cell proliferation studies using human airway smooth muscle cells
      demonstrated that cells homozygous for the deleterious allele proliferate at a
      faster rate than those homozygous for the protective allele.

PMID- 20028936
TI  - Are elite endurance athletes genetically predisposed to lower disease risk?
AB  - We compared a polygenic profile that combined 33 disease risk-related mutations
      and polymorphisms among nonathletic healthy control subjects and elite endurance
      athletes. The study sample comprised 100 healthy Spanish male nonathletic
      (sedentary) control subjects and 100 male elite endurance athletes. We analyzed
      33 disease risk-related mutations and polymorphisms. We computed a health-related
      total genotype score (TGS, 0-100) from the accumulated combination of the 33
      variants. We did not observe significant differences in genotype or allele
      distributions among groups, except for the rs4994 polymorphism (P < 0.001). The
      computed health-related TGS was similar among groups (23.8 +/- 1.0 vs. 24.2 +/-
      0.8 in control subjects and athletes, respectively; P = 0.553). Similar results
      were obtained when computing specific TGSs for each main disease category
      (cardiovascular disease and cancer). We observed no evidence that male elite
      endurance athletes are genetically predisposed to have lower disease risk than
      matched nonathletic control subjects.

PMID- 20028937
TI  - Regulatory T cell-mediated resolution of lung injury: identification of potential
      target genes via expression profiling.
AB  - In animal models of acute lung injury (ALI), gene expression studies have focused
      on the acute phase of illness, with little emphasis on resolution. In this study,
      the acute phase of intratracheal lipopolysaccharide (IT LPS)-induced lung injury
      was similar in wild-type (WT) and recombinase-activating gene-1-deficient (Rag-1(
      /-)) lymphocyte-deficient mice, but resolution was impaired and resolution-phase
      lung gene expression remained different from baseline only in Rag-1(-/-) mice. By
      focusing on groups of genes involved in similar biological processes (gene
      ontologies) pertinent to inflammation and the immune response, we identified 102
      genes at days 4 and 10 after IT LPS with significantly different expression
      between WT and Rag-1(-/-) mice. After adoptive transfer of isolated
      CD4+CD25+Foxp3+ regulatory T cells (Tregs) to Rag-1(-/-) mice at the time of IT
      LPS, resolution was similar to that in WT mice. Of the 102 genes distinctly
      changed in either WT or Rag-1(-/-) mice from our 7 gene ontologies, 19 genes
      reverted from the Rag-1(-/-) to the WT pattern of expression after adoptive
      transfer of Tregs, implicating those 19 genes in Treg-mediated resolution of ALI.

PMID- 20028938
TI  - Lack of lipotoxicity effect on {beta}-cell dysfunction in ketosis-prone type 2
      diabetes.
AB  - OBJECTIVE Over half of newly diagnosed obese African Americans with diabetic
      ketoacidosis (DKA) discontinue insulin therapy and go through a period of near
      normoglycemia remission. This subtype of diabetes is known as ketosis-prone type
      2 diabetes (KPDM). RESEARCH DESIGN AND METHODS To investigate the role of
      lipotoxicity on beta-cell function, eight obese African Americans with KPDM,
      eight obese subjects with type 2 diabetes with severe hyperglycemia without
      ketosis (ketosis-resistant type 2 diabetes), and nine nondiabetic obese control
      subjects underwent intravenous infusion of 20% intralipid at 40 ml/h for 48 h.
      beta-Cell function was assessed by changes in insulin and C-peptide concentration
      during infusions and by changes in acute insulin response to arginine stimulation
      (AIR(arg)) before and after lipid infusion. RESULTS The mean time to discontinue
      insulin therapy was 11.0 +/- 8.0 weeks in KPDM and 9.6 +/- 2.2 weeks in ketosis
      resistant type 2 diabetes (P = NS). At remission, KPDM and ketosis-resistant type
      2 diabetes had similar glucose (94 +/- 14 vs. 109 +/- 20 mg/dl), A1C (5.7 +/- 0.4
      vs. 6.3 +/- 1.1%), and baseline AIR(arg) response (34.8 +/- 30 vs. 64 +/- 69
      microU/ml). P = NS despite a fourfold increase in free fatty acid (FFA) levels
      (0.4 +/- 0.3 to 1.8 +/- 1.1 mmol/l, P < 0.01) during the 48-h intralipid
      infusion; the response to AIR(arg) stimulation, as well as changes in insulin and
      C-peptide levels, were similar among obese patients with KPDM, patients with
      ketosis-resistant type 2 diabetes, and nondiabetic control subjects. CONCLUSIONS
      Near-normoglycemia remission in obese African American patients with KPDM and
      ketosis-resistant type 2 diabetes is associated with a remarkable recovery in
      basal and stimulated insulin secretion. A high FFA level by intralipid infusion
      for 48 h was not associated with beta-cell decompensation (lipotoxicity) in KPDM
      patients.

PMID- 20028939
TI  - Six months of diazoxide treatment at bedtime in newly diagnosed subjects with
      type 1 diabetes does not influence parameters of {beta}-cell function and
      autoimmunity but improves glycemic control.
AB  - OBJECTIVE Continuous beta-cell rest with diazoxide preserves residual endogenous
      insulin production in type 1 diabetes. However, side effects have hampered
      therapeutic usefulness. In a double-blind study, we tested whether lower,
      intermittent dosing of diazoxide had beneficial effects on insulin production,
      metabolic control, and autoimmunity markers in the absence of side effects.
      RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients
      were randomized to 6 months of treatment with placebo or 100 mg diazoxide at
      bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3(+)
      regulatory T-cells (Tregs) were measured. Patients were followed for 6 months
      after intervention. RESULTS Of six dropouts, three were due to perceived side
      effects; one subject in the diazoxide group experienced rash, another dizziness,
      and one in the placebo group sleep disturbance. Adverse effects in others were
      absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months
      and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3,
      and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and
      stimulated C-peptide decreased during 12 months similarly in both arms (mean 
      0.30 and -0.18 nmol/l in the diazoxide arm and -0.08 and -0.09 nmol/l in the
      placebo arm). The proportion of Tregs was similar in both arms and remained
      stable during intervention but was significantly lower compared with nondiabetic
      subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects
      and did not measurably affect insulin production but was associated with improved
      metabolic control.

PMID- 20028940
TI  - Islet cell antibody-positive versus -negative phenotypic type 2 diabetes in
      youth: does the oral glucose tolerance test distinguish between the two?
AB  - OBJECTIVE Using the clamp technique, youths with a clinical diagnosis of type 2
      diabetes (CDx-type 2 diabetes) and positive pancreatic autoantibodies (Ab(+))
      were shown to have severe impairment in insulin secretion and less insulin
      resistance than their peers with negative antibodies (Ab(-)). In this study, we
      investigated whether oral glucose tolerance test (OGTT)-derived indexes of
      insulin secretion and sensitivity could distinguish between these two groups.
      RESEARCH DESIGN AND METHODS A total of 25 Ab(-), 11 Ab(+) CDx-type 2 diabetic,
      and 21 obese control youths had an OGTT. Fasting and OGTT-derived indexes of
      insulin sensitivity (including the Matsuda index, homeostasis model assessment
      [HOMA] of insulin resistance, quantitative insulin sensitivity check index, and
      glucose-to-insulin ratio) and insulin secretion (HOMA of insulin secretion and 30
      min insulogenic and C-peptide indexes) were used. Glucagon and glucagon-like
      peptide (GLP)-1 responses were assessed. RESULTS Fasting C-peptide and C-peptide
      to-glucose ratio, and C-peptide area under the curve (AUC) were significantly
      lower in the Ab(+) CDx-type 2 diabetic patients. Other OGTT-derived surrogate
      indexes of insulin sensitivity and secretion were not different between the Ab(+)
      versus Ab(-) patients. GLP-1 during the OGTT was highest in the Ab(+) youths
      compared with the other two groups, but this difference disappeared after
      adjusting for BMI. Ab(+) and Ab(-) CDx-type 2 diabetes had relative
      hyperglucagonemia compared with control subjects. CONCLUSIONS The clinical
      measures of fasting and OGTT-derived surrogate indexes of insulin sensitivity and
      secretion, except for fasting C-peptide and C-peptide AUC, are less sensitive
      tools to distinguish metabolic/pathopysiological differences, detected by the
      clamp, between Ab(+) and Ab(-) CDx-type 2 diabetic youths. This underscores the
      importance of using more sensitive methods and the importance of determining
      antibody status in obese youths with CDx-type 2 diabetes.

PMID- 20028941
TI  - Marked hypotonia in an infant of a mother with Devic disease.
AB  - A full-term female neonate was born with severe hypotonia and weakness. Her
      mother had been treated for neuromyelitis optica (Devic disease) for 6 years. Her
      previous son, born 10 years earlier and before she developed the disease, also
      had marked hypotonia that gradually improved over several weeks. A suspicion of
      neonatal myasthenia gravis arose, as a search of the literature revealed the
      occasional detection of anti-acetylcholine receptor antibodies in patients with
      Devic disease. A neostigmine test was mildly positive in the baby, but anti
      acetylcholine receptor antibodies were elevated. Aquaporin 4 antibodies typical
      of neuromyelitis optica were not detected in the infant. Because of clinical
      deterioration, intravenous immunoglobulin was administered with substantial
      improvement. Anti-acetylcholine antibodies were markedly elevated in the mother's
      serum, although she showed no clinical signs of myasthenia gravis. It is very
      likely that her previous baby also had unrecognized transient myasthenia gravis.

PMID- 20028942
TI  - Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2
      deficient mice.
AB  - OBJECTIVE: Mice with complete deletion of insulin receptor substrate 2 (IRS2)
      develop hyperglycemia, impaired hepatic insulin signaling, and elevated
      gluconeogenesis, whereas mice deficient for protein tyrosine phosphatase (PTP)1B
      display an opposing hepatic phenotype characterized by increased sensitivity to
      insulin. To define the relationship between these two signaling pathways in the
      regulation of liver metabolism, we used genetic and pharmacological approaches to
      study the effects of inhibiting PTP1B on hepatic insulin signaling and expression
      of gluconeogenic enzymes in IRS2(-/-) mice. RESEARCH DESIGN AND METHODS: We
      analyzed glucose homeostasis and insulin signaling in liver and isolated
      hepatocytes from IRS2(-/-) and IRS2(-/-)/PTP1B(-/-) mice. Additionally, hepatic
      insulin signaling was assessed in control and IRS2(-/-) mice treated with
      resveratrol, an antioxidant present in red wine. RESULTS: In livers of
      hyperglycemic IRS2(-/-) mice, the expression levels of PTP1B and its association
      with the insulin receptor (IR) were increased. The absence of PTP1B in the double
      mutant mice restored hepatic IRS1-mediated phosphatidylinositol (PI) 3
      kinase/Akt/Foxo1 signaling. Moreover, resveratrol treatment of hyperglycemic
      IRS2(-/-) mice decreased hepatic PTP1B mRNA and inhibited PTP1B activity, thereby
      restoring IRS1-mediated PI 3-kinase/Akt/Foxo1 signaling and peripheral insulin
      sensitivity. CONCLUSIONS: By regulating the phosphorylation state of IR, PTB1B
      determines sensitivity to insulin in liver and exerts a unique role in the
      interplay between IRS1 and IRS2 in the modulation of hepatic insulin action.

PMID- 20028943
TI  - Cerebral metabolic alterations in rats with diabetic ketoacidosis: effects of
      treatment with insulin and intravenous fluids and effects of bumetanide.
AB  - OBJECTIVE: Cerebral edema is a life-threatening complication of diabetic
      ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion
      and activation of cerebral ion transporters may be involved, but data describing
      cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND
      METHODS: We evaluated 50 juvenile rats with DKA and 21 normal control rats using
      proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured
      cerebral intracellular pH and ratios of metabolites including ATP/inorganic
      phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr),
      and lactate/Cr before and during DKA treatment. We determined the effects of
      treatment with insulin and intravenous saline with or without bumetanide, an
      inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 x 2 factorial study
      design. RESULTS: Cerebral intracellular pH was decreased during DKA compared with
      control (mean +/- SE difference -0.13 +/- 0.03; P < 0.001), and lactate/Cr was
      elevated (0.09 +/- 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (-0.32
      +/- 0.10, P = 0.003, and -0.14 +/- 0.04, P < 0.001, respectively) compared with
      controls, but PCr/Pi was not significantly decreased. During 2-h treatment with
      insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an
      increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi
      and ameliorated the declines in these values with insulin/saline treatment.
      CONCLUSIONS: These data demonstrate that cerebral metabolism is significantly
      compromised during DKA and that further deterioration occurs during early DKA
      treatment--consistent with possible effects of cerebral hypoperfusion and
      reperfusion injury. Treatment with bumetanide may help diminish the adverse
      effects of initial treatment with insulin/saline.

PMID- 20028944
TI  - Gene variants of TCF7L2 influence weight loss and body composition during
      lifestyle intervention in a population at risk for type 2 diabetes.
AB  - OBJECTIVE: The impact of the diabetes risk gene transcription factor 7-like 2
      (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and
      involved in Wnt-dependent regulation of adipogenesis, we studied the impact of
      TCF7L2 variants on body composition and weight loss during lifestyle
      intervention. RESEARCH DESIGN AND METHODS: We genotyped 309 German subjects at
      increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs)
      rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral
      glucose tolerance tests before and after a 9-month lifestyle intervention. Fat
      distribution was quantified using whole-body magnetic resonance
      imaging/spectroscopy in a subgroup of 210 subjects. RESULTS: After adjustment for
      confounding variables, we observed a negative impact of the type 2 diabetes
      allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in
      nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle
      intervention. An association of rs7903146 with lifestyle intervention-induced
      changes in insulin secretion, glucose concentrations, liver fat, or insulin
      sensitivity were not detected (all P > 0.2). Essentially the same results were
      obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205
      and rs7895340 on change in BMI (all P > or = 0.5). CONCLUSIONS: Our data reveal
      that diabetes-associated alleles of TCF7L2 are associated with less weight loss
      in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene
      variation predicts the success of lifestyle intervention in terms of weight loss
      and determines individual susceptibility toward environmental factors.

PMID- 20028945
TI  - Metabolic changes following a 1-year diet and exercise intervention in patients
      with type 2 diabetes.
AB  - OBJECTIVE: To characterize the relationships among long-term improvements in
      peripheral insulin sensitivity (glucose disposal rate [GDR]), fasting glucose,
      and free fatty acids (FFAs) and concomitant changes in weight and adipose tissue
      mass and distribution induced by lifestyle intervention in obese individuals with
      type 2 diabetes. RESEARCH DESIGN AND METHODS: We measured GDR, fasting glucose,
      and FFAs during a euglycemic clamp and adipose tissue mass and distribution,
      organ fat, and adipocyte size by dual-energy X-ray absorptiometry, CT scan, and
      adipose tissue biopsy in 26 men and 32 women in the Look-AHEAD trial before and
      after 1 year of diet and exercise aimed at weight loss. RESULTS: Weight and
      fasting glucose decreased significantly (P < 0.0001) and significantly more in
      men than in women (-12 vs. -8% and -16 vs. -7%, respectively; P < 0.05), while
      FFAs during hyperinsulinemia decreased and GDR increased significantly (P <
      0.00001) and similarly in both sexes (-53 vs. -41% and 63 vs. 43%; P = NS). Men
      achieved a more favorable fat distribution by losing more from upper compared
      with lower and from deeper compared with superficial adipose tissue depots (P <
      0.01). Decreases in weight and adipose tissue mass predicted improvements in GDR
      but not in fasting glucose or fasting FFAs; however, decreases in FFAs during
      hyperinsulinemia significantly determined GDR improvements. Hepatic fat was the
      only regional fat measure whose change contributed independently to changes in
      metabolic variables. CONCLUSIONS: Patients with type 2 diabetes undergoing a 1
      year lifestyle intervention had significant improvements in GDR, fasting glucose,
      FFAs and adipose tissue distribution. However, changes in overall weight (adipose
      tissue mass) and hepatic fat were the most important determinants of metabolic
      improvements.

PMID- 20028946
TI  - Insulin acutely inhibits intestinal lipoprotein secretion in humans in part by
      suppressing plasma free fatty acids.
AB  - OBJECTIVE: Intestinal lipoprotein production has recently been shown to be
      increased in insulin resistance, but it is not known whether it is regulated by
      insulin in humans. Here, we investigated the effect of acute hyperinsulinemia on
      intestinal (and hepatic) lipoprotein production in six healthy men in the
      presence and absence of concomitant suppression of plasma free fatty acids
      (FFAs). RESEARCH DESIGN AND METHODS: Each subject underwent the following three
      lipoprotein turnover studies, in random order, 4-6 weeks apart: 1) insulin and
      glucose infusion (euglycemic-hyperinsulinemic clamp) to induce hyperinsulinemia,
      2) insulin and glucose infusion plus Intralipid and heparin infusion to prevent
      the insulin-induced suppression of plasma FFAs, and 3) saline control. RESULTS:
      VLDL1 and VLDL2-apoB48 and -apoB100 production rates were suppressed by 47-62% by
      insulin, with no change in clearance. When the decline in FFAs was prevented by
      concomitant infusion of Intralipid and heparin, the production rates of VLDL1 and
      VLDL2-apoB48 and -apoB100 were intermediate between insulin and glucose infusion
      and saline control. CONCLUSIONS: This is the first demonstration in humans that
      intestinal apoB48-containing lipoprotein production is acutely suppressed by
      insulin, which may involve insulin's direct effects and insulin-mediated
      suppression of circulating FFAs.

PMID- 20028947
TI  - Detailed investigation of the role of common and low-frequency WFS1 variants in
      type 2 diabetes risk.
AB  - OBJECTIVE: Wolfram syndrome 1 (WFS1) single nucleotide polymorphisms (SNPs) are
      associated with risk of type 2 diabetes. In this study we aimed to refine this
      association and investigate the role of low-frequency WFS1 variants in type 2
      diabetes risk. RESEARCH DESIGN AND METHODS: For fine-mapping, we sequenced WFS1
      exons, splice junctions, and conserved noncoding sequences in samples from 24
      type 2 diabetic case and 68 control subjects, selected tagging SNPs, and
      genotyped these in 959 U.K. type 2 diabetic case and 1,386 control subjects. The
      same genomic regions were sequenced in samples from 1,235 type 2 diabetic case
      and 1,668 control subjects to compare the frequency of rarer variants between
      case and control subjects. RESULTS: Of 31 tagging SNPs, the strongest associated
      was the previously untested 3' untranslated region rs1046320 (P = 0.008); odds
      ratio 0.84 and P = 6.59 x 10(-7) on further replication in 3,753 case and 4,198
      control subjects. High correlation between rs1046320 and the original strongest
      SNP (rs10010131) (r2 = 0.92) meant that we could not differentiate between their
      effects in our samples. There was no difference in the cumulative frequency of 82
      rare (minor allele frequency [MAF] <0.01) nonsynonymous variants between type 2
      diabetic case and control subjects (P = 0.79). Two intermediate frequency (MAF
      0.01-0.05) nonsynonymous changes also showed no statistical association with type
      2 diabetes. CONCLUSIONS: We identified six highly correlated SNPs that show
      strong and comparable associations with risk of type 2 diabetes, but further
      refinement of these associations will require large sample sizes (>100,000) or
      studies in ethnically diverse populations. Low frequency variants in WFS1 are
      unlikely to have a large impact on type 2 diabetes risk in white U.K.
      populations, highlighting the complexities of undertaking association studies
      with low-frequency variants identified by resequencing.

PMID- 20028948
TI  - Restoration of muscle mitochondrial function and metabolic flexibility in type 2
      diabetes by exercise training is paralleled by increased myocellular fat storage
      and improved insulin sensitivity.
AB  - OBJECTIVE: Mitochondrial dysfunction and fat accumulation in skeletal muscle
      (increased intramyocellular lipid [IMCL]) have been linked to development of type
      2 diabetes. We examined whether exercise training could restore mitochondrial
      function and insulin sensitivity in patients with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: Eighteen male type 2 diabetic and 20 healthy male control
      subjects of comparable body weight, BMI, age, and VO2max participated in a 12
      week combined progressive training program (three times per week and 45 min per
      session). In vivo mitochondrial function (assessed via magnetic resonance
      spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect
      calorimetry), and IMCL content (histochemically) were measured before and after
      training. RESULTS: Mitochondrial function was lower in type 2 diabetic compared
      with control subjects (P = 0.03), improved by training in control subjects (28%
      increase; P = 0.02), and restored to control values in type 2 diabetic subjects
      (48% increase; P < 0.01). Insulin sensitivity tended to improve in control
      subjects (delta Rd 8% increase; P = 0.08) and improved significantly in type 2
      diabetic subjects (delta Rd 63% increase; P < 0.01). Suppression of insulin
      stimulated endogenous glucose production improved in both groups (-64%; P < 0.01
      in control subjects and -52% in diabetic subjects; P < 0.01). After training,
      metabolic flexibility in type 2 diabetic subjects was restored (delta respiratory
      exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects
      (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with
      comparable pretraining IMCL levels, training tended to increase IMCL content in
      type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle
      fibers. CONCLUSIONS: Exercise training restored in vivo mitochondrial function in
      type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic
      flexibility improved in type 2 diabetic subjects in the face of near
      significantly increased IMCL content. This indicates that increased capacity to
      store IMCL and restoration of improved mitochondrial function contribute to
      improved muscle insulin sensitivity.

PMID- 20028949
TI  - Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and
      mode of onset.
AB  - OBJECTIVE: Relatives of type 1 diabetic patients are at enhanced risk of
      developing diabetes. We investigated the mode of onset of hyperglycemia and how
      insulin sensitivity and beta-cell function contribute to the progression to the
      disease. RESEARCH DESIGN AND METHODS: In 328 islet cell autoantibody-positive,
      nondiabetic relatives from the observational arms of the Diabetes Prevention
      Trial-1 Study (median age 11 years [interquartile range 8], sequential OGTTs
      (2,143 in total) were performed at baseline, every 6 months, and 2.7 years [2.7]
      later, when 115 subjects became diabetic. Beta-cell glucose sensitivity (slope of
      the insulin-secretion/plasma glucose dose-response function) and insulin
      sensitivity were obtained by mathematical modeling of the OGTT glucose/C-peptide
      responses. RESULTS: In progressors, baseline insulin sensitivity, fasting insulin
      secretion, and total postglucose insulin output were similar to those of
      nonprogressors, whereas beta-cell glucose sensitivity was impaired (median 48
      pmol/min per m2 per mmol/l [interquartile range 36] vs. 87 pmol/min per m2 per
      mmol/l [67]; P < 0.0001) and predicted incident diabetes (P < 0.0001)
      independently of sex, age, BMI, and clinical risk. In progressors, 2-h glucose
      levels changed little until 0.78 years before diagnosis, when they started to
      rise rapidly (approximately 13 mmol x l(-1) x year(-1)); glucose sensitivity
      began to decline significantly (P < 0.0001) earlier (1.45 years before diagnosis)
      than the plasma glucose surge. During this anticipation phase, both insulin
      secretion and insulin sensitivity were essentially stable. CONCLUSIONS: In high
      risk relatives, beta-cell glucose sensitivity is impaired and is a strong
      predictor of diabetes progression. The time trajectories of plasma glucose are
      frequently biphasic, with a slow linear increase followed by a rapid surge, and
      are anticipated by a further deterioration of beta-cell glucose sensitivity.

PMID- 20028950
TI  - Measuring the impact of diabetes on life expectancy and disability-free life
      expectancy among older adults in Mexico.
AB  - OBJECTIVES. The aim of the present study is to investigate differences in total
      life expectancy (TLE), disability-free life expectancy (DFLE), disabled life
      expectancy (DLE), and personal care assistance between individuals with and
      without diabetes in Mexico. METHODS: The sample was drawn from the nationally
      representative Mexican Health and Aging Study. Disability was assessed through a
      basic Activities of Daily Living (ADL) measure, the Instrumental Activities of
      Daily Living (IADL) scale, and the Nagi physical performance measure. The
      Interpolation of Markov Chains method was used to estimate the impact of diabetes
      on TLE and DFLE. RESULTS: Results indicate that diabetes reduces TLE at ages 50
      and 80 by about 10 and 4 years, respectively. Diabetes is also associated with
      fewer years in good health. DFLE (based on ADL measures) at age 50 is 20.8 years
      (95% confidence interval [CI]: 19.2-22.3) for those with diabetes, compared with
      29.9 years (95% CI: 28.8-30.9) for those without diabetes. Regardless of diabetes
      status, Mexican women live longer but face a higher disability burden than men.
      CONCLUSION: Among older adults in Mexico, diabetes is associated with shorter TLE
      and DFLE. The negative effect of diabetes on the number of years lived,
      particularly in good health, creates significant economic, social, and individual
      costs for elderly Mexicans.

PMID- 20028951
TI  - Longitudinal association between self-rated health and timed gait among older
      persons.
AB  - OBJECTIVE: We evaluated the longitudinal association between self-rated health
      (SRH) and timed gait, an indicator of lower extremity dysfunction, in a community
      based sample of older persons. METHODS: Participants (N = 754) were evaluated at
      18-month intervals for 72 months. SRH was categorized as Excellent/Very Good/Good
      and Fair/Poor. Participants were asked to walk a 10-foot course "as fast as it
      feels safe and comfortable," turn around, and walk back, with timed gait defined
      as normal (<=10 s) or slow (>10 s). Generalized multinomial logit models,
      adjusted for demographic features, biomedical and psychosocial factors, and
      activities of daily living, evaluated the association between SRH and the
      likelihood of 6 possible transitions (from normal or slow timed gait to normal
      timed gait, slow timed gait, or death) over time. We also ran a repeated measures
      linear mixed model with change in timed gait as the outcome. RESULTS: Compared
      with participants reporting Excellent/Very Good/Good SRH, those reporting
      Fair/Poor SRH were more likely to transition from normal to slow timed gait or to
      death. SRH was not associated with transitions from slow timed gait to normal
      timed gait or to death. In addition, time to complete the gait task increased
      (i.e., slowed) over time among participants reporting Fair/Poor SRH compared with
      those reporting Excellent/Very Good/Good SRH. DISCUSSION: Among older persons,
      SRH is associated with the development of lower extremity dysfunction but not
      with recovery from lower extremity dysfunction. This relationship may indicate an
      intermediate step in the pathway from SRH to mortality.

PMID- 20028952
TI  - Is it better to give or to receive? Social support and the well-being of older
      adults.
AB  - OBJECTIVES. This study examines the separate effects of several dimensions of
      giving and receiving social support on the well-being of older adults, with
      hypotheses guided by identity theory. METHODS: Data derive from the Social
      Networks in Adult Life survey, a national probability sample of older adults (N =
      689). Ordinary least squares regression was used to examine the impact of total
      support, size of support network, number of types of support, and types of alter
      support relationships-both given and received-on well-being. RESULTS: Providing
      support to others is beneficial to older adults' well-being, as illustrated in
      the relatively strong, positive associations of total support given, the number
      of types of support given, and support given to friends and children on well
      being. Receiving support was less important to well-being except when received
      from a spouse or sibling. CONCLUSION: Evidence from this analysis provides
      support for hypotheses predicted by identity theory, highlights the importance of
      examining giving and receiving support net of the other, and suggests that it is
      often better for the well-being of older adults to give than to receive.

PMID- 20028953
TI  - Comment: Drug-drug interaction between clopidogrel and the proton pump
      inhibitors.

PMID- 20028954
TI  - Candida meningitis post Gliadel wafer placement successfully treated with
      intrathecal and intravenous amphotericin B.
AB  - OBJECTIVE: To report a case of Candida meningitis post Gliadel wafer
      (polifeprosan 20 with carmustine implant) placement successfully treated with the
      combination of intrathecal and intravenous amphotericin B. CASE SUMMARY: A 33
      year-old white female with a history of recurrent oligodendroglioma was admitted
      to the neuroscience intensive care unit with acute mental status changes.
      Computed tomography of the head demonstrated a cystic dilation of the right
      frontoparietal tumor resection cavity with Gliadel wafers in place and the
      presence of a large fluid collection. The cavity was debrided surgically and a
      ventriculostomy catheter was left in place. Cerebrospinal fluid (CSF) cultures
      were positive for Candida albicans and methicillin-resistant coagulase-negative
      Staphylococcus spp. Antiinfective therapy with intrathecal and intravenous
      amphotericin B as well as flucytosine and vancomycin was started. The patient had
      subsequent improvement in clinical manifestations, resolution of CSF
      leukocytosis, and mycologic cure. DISCUSSION: Candida meningitis occurs primarily
      in the setting of immunosuppression, intravenous drug abuse and following
      neurosurgical procedures. Secondary bacterial and fungal infections have been
      reported following Gliadel wafer placement in patients with brain tumor
      resection. Candida meningitis has traditionally been treated with intravenous
      amphotericin B with or without oral flucytosine. There have been reports of
      treatment with intrathecal amphotericin B with variable clinical outcomes.
      CONCLUSIONS: This case demonstrates successful treatment of Candida meningitis
      post Gliadel wafer placement with the combination of intrathecal and intravenous
      amphotericin B. This treatment modality may provide an effective therapeutic
      option for other patients with Candida meningitis, especially those unresponsive
      to intravenous therapy.

PMID- 20028955
TI  - Characterizing hospitalizations of end-stage renal disease patients on dialysis
      and inpatient utilization of erythropoiesis-stimulating agent therapy.
AB  - BACKGROUND: In 2006, there were over 350,000 patients with end-stage renal
      disease (ESRD) receiving dialysis therapy. Studies have found that hemoglobin
      concentrations are often low among dialysis patients after hospital discharge,
      yet little is known about inpatient anemia treatment. OBJECTIVE: To characterize
      hospitalizations among patients with ESRD on dialysis, specifically, inpatient
      utilization of erythropoiesis-stimulating agent (ESA) therapy. METHODS: A cross
      sectional, retrospective study of claims data from 5 commercial health plans for
      the years 2004-2006 was conducted. Inclusion criteria included 1 or more ESRD
      specific International Classification of Diseases Ninth Edition (ICD-9) codes, 3
      or more ESRD-specific Current Procedural Terminology/Healthcare Common Procedure
      Coding System (CPT/HCPCS) procedures on different days, or 3 or more dialysis ICD
      9 codes or CPT/HCPCS dialysis procedures on separate days. ESRD patient and
      hospital characteristics were outlined. RESULTS: ESRD patients were hospitalized
      an average of 1.8 times in both 2004-2005 and 2005-2006. The mean +/- SD hospital
      length of stay (LOS) was 13.3 +/- 20.5 and 12.8 +/- 19.0 days for 2004-2005 and
      2005-2006, respectively. For each year, LOS greater than 7 days occurred in 44%
      of hospitalizations. Many of these patients were admitted for kidney-related
      comorbidities and ultimately received procedures and services relevant to
      dialysis care. For each year, ESA utilization was 13% in year 1 and 11% in year 2
      across any LOS. For ESRD patients with a 4- to 7-day LOS (the most common LOS),
      less than 20% received ESA treatment. ESA utilization increased correspondingly
      with longer hospital LOS (p < 0.001). CONCLUSIONS: Although ESRD patients are
      commonly hospitalized and claims recognize that kidney-related conditions exist,
      the utilization of ESAs is low.

PMID- 20028956
TI  - Stability of mesna in ReadyMed infusion devices.

PMID- 20028957
TI  - A pharmacist and health promoter team to improve medication adherence among
      Latinos with diabetes.
AB  - BACKGROUND: There is a need to improve blood glucose levels of underserved Latino
      patients with uncontrolled diabetes. OBJECTIVE: To determine the feasibility of a
      pharmacist and health promoter team designed to address the barriers to
      medication adherence and adjustment and improve self-care among Latinos with type
      2 diabetes. METHODS: Clinical staff at the University of Illinois at Chicago
      Medical Center referred Latino patients with uncontrolled diabetes (hemoglobin
      A(1c) [A1C] > or =8.0%) to the study. A research assistant assessed patients on
      diabetes and medical history, medication list, medication adherence and related
      habits, health literacy, diabetes knowledge and numeracy, beliefs in benefits of
      diabetes therapy, depression, social support, and access to care. A bilingual,
      bicultural health promoter reviewed these assessments and worked with patients
      through home and clinic visits and telephone calls. The health promoter
      communicated with a pharmacist to receive assistance in medication management
      (reconciliation and adjustment). Participants received case management for 6
      months. RESULTS: Nine patients were successfully recruited. The mean age was 58
      years and mean duration of diabetes was 21 years. Successful collaboration
      between pharmacists and the health promoter required frequent communication and
      intense effort to address complex patient barriers. Health promoter contact time,
      in person, per participant ranged from 0 minutes to 640 minutes, and telephone
      call time ranged from 27 minutes to 111 minutes during the study period. Eight
      participants had medication adjustments during the study period, with a maximum
      of 7 adjustments per participant. Mean hemoglobin A1C declined from an average of
      9.6% to 9.0%. Two patients are presented as case studies to describe how the
      pharmacist-health promoter team functioned. Information was obtained from health
      promoter records, survey results, and chart reviews. CONCLUSIONS: The pharmacist
      and health promoter team management of uncontrolled diabetes among Latinos
      appears to be a feasible approach to improving medication management.

PMID- 20028958
TI  - Evaluation of inpatient admissions and potential antimicrobial and analgesic
      dosing errors in overweight children.
AB  - BACKGROUND: The prevalence of overweight/obesity in US children has increased
      over the past several decades. Routine use of weight-based dosing of medications
      could potentially result in over- or underdosing in these children. OBJECTIVE: To
      determine the percentage of admissions of children with a body mass index (BMI)
      greater than or equal to the 85th percentile for age and sex and the mean error
      rate per admission in the overweight versus control group. METHODS: We performed
      a retrospective, preliminary study of children aged 5-12 years who were admitted
      to a children's hospital over a period of 6 months. The overweight group included
      children with a BMI greater than or equal to the 85th percentile; the control
      group included children with a BMI less than the 85th percentile. Dose
      appropriateness was assessed, using 2 references. An overdose was defined as: (1)
      total mg/kg/day or mg/kg/dose greater than or equal to 110% of the maximum
      recommended pediatric dose, (2) total mg/day greater than the adult maximum
      recommended dose, or (3) greater than the recommended number of doses per day. An
      underdose was defined as: (1) total mg/kg/day or mg/kg/dose less than or equal to
      90% of the minimum recommended pediatric dose, or (2) fewer than the recommended
      number of doses per day. Baseline comparisons between groups were done via
      Student's t-tests and chi2 analysis, when appropriate, with an a priori alpha of
      p less than or equal to 0.05. RESULTS: A total of 839 admissions representing 699
      patients were included. The overweight group included 278 (33.1%) admissions.
      Comparison of overall mean error rate per admission revealed a statistically
      significant increase in dosing errors for overweight patients (0.4 +/- 0.6 vs 0.3
      +/- 0.6; p = 0.030), with underdose errors occurring more frequently than
      overdose errors (0.3 +/- 0.6 vs 0.2 +/- 0.5; p = 0.010). CONCLUSIONS: Overweight
      children accounted for one-third of admissions, and the results of this study
      suggest that these patients are at greater risk for errors in dosing than are
      children of age- and sex-appropriate weight. This study did not assess clinical
      outcomes; however, overweight children could be at increased risk for therapeutic
      failures or adverse effects.

PMID- 20028959
TI  - Melatonin treatment for insomnia in pediatric patients with attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: To evaluate the efficacy and safety of melatonin for the treatment of
      insomnia in pediatric patients with attention-deficit/hyperactivity disorder
      (ADHD). DATA SOURCES: Literature was accessed through MEDLINE (1948-August 2009),
      EMBASE (1950-August 2009), and Scopus (1960-August 2009) using the terms
      melatonin, attention-deficit/hyperactivity disorder (ADHD), pediatric, insomnia,
      sleep disorder, and sleep. In addition, reference citations from publications
      identified were reviewed for relevant information. STUDY SELECTION AND DATA
      EXTRACTION: All English-language articles and human studies were identified and
      evaluated. Results from all identified randomized trials (n = 5), safety studies
      (n = 1), long-term follow-up studies (n = 1), post hoc retrospective analyses (n
      = 1), meta-analyses (n = 2), review articles (n = 9), and letters (n = 1) were
      summarized. DATA SYNTHESIS: Pediatric insomnia is prevalent in children with ADHD
      and impacts academic performance, social functioning, overall health, and family
      life. First-line therapy includes ruling out differential diagnoses, optimizing
      ADHD stimulant treatment, and initiating good sleep hygiene and behavioral
      therapy. Adjuvant pharmacotherapy is then an option and melatonin is often
      prescribed. Melatonin regulates circadian rhythm sleep disorders such as sleep
      onset insomnia (SOI) in children with ADHD. Four studies in children with ADHD
      and insomnia showed improvement in sleep onset and sleep latency. Studies
      included children 6-14 years old and melatonin doses ranged from 3 to 6 mg
      administered within a few hours of a scheduled bedtime. In all studies, adverse
      events were transient and mild. The available melatonin studies are limited by
      small size and short duration; variable SOI criteria, ADHD criteria, and
      treatment assessments; and lack of generalizability. CONCLUSIONS: Available data
      suggest that melatonin is a well-tolerated and efficacious treatment option for
      pediatric patients with chronic SOI and ADHD. Regulated melatonin products and
      larger, well-designed trials to establish optimal dosing regimens and long-term
      safety are needed.

PMID- 20028960
TI  - Effect of a pharmacy-based health literacy intervention and patient
      characteristics on medication refill adherence in an urban health system.
AB  - BACKGROUND: Limited health literacy is associated with poor understanding of
      medication instructions and may be related to medication adherence. OBJECTIVE: To
      evaluate a 3-part intervention (automated telephone reminder calls to refill
      prescriptions, picture prescription card, and clear health communication training
      for pharmacists) intended to increase refill adherence through attention to
      health literacy. METHODS: Three pharmacies that serve a primarily indigent,
      minority population served as the intervention sites, and one pharmacy served as
      the control site. To evaluate the impact of the 6-month intervention on
      medication adherence, pharmacy refill data were used to calculate the cumulative
      medication gap (CMG), in which values close to zero indicate better adherence.
      The primary measure of treatment effect was a comparison of the change in refill
      adherence within each group, from baseline to follow-up. RESULTS: A total of 173
      patients were enrolled in the intervention group and 102 patients in the control
      group. Medication adherence was significantly different between intervention (CMG
      = 0.25) and control (CMG = 0.18) groups at baseline (p = 0.004). Refill adherence
      in the intervention group improved slightly during follow-up (CMG = 0.23), while
      it worsened slightly in the control group (CMG = 0.21), but the change in
      adherence between intervention and control groups was not significantly different
      (p = 0.4). Between 80% and 90% of intervention participants indicated that
      receiving the picture prescription and phone call interventions helped them
      remember when and how to take their medications and refill their prescriptions.
      No patient characteristics, including health literacy, were consistently
      associated with adherence. CONCLUSIONS: Implementation of a 3-part intervention-
      automated telephone reminders, picture prescription card, and pharmacist
      communication skills training--did not significantly improve refill adherence
      among inner-city patients. Further study should explore whether other aspects of
      medication management, such as dosing or adverse events, can be improved through
      these types of interventions, implemented either alone or in combination.

PMID- 20028961
TI  - Evaluation of a pharmacist-managed telephone lipid clinic at a Veterans Affairs
      Medical Center.
AB  - BACKGROUND: Heart disease is one of the leading causes of death and disability in
      the US, with dyslipidemia being a significant risk factor. Pharmacist-managed
      lipid clinics have been shown to be effective in lowering low-density lipoprotein
      cholesterol (LDL-C) values in the veteran population. In addition, telephone
      managed clinics are known to be an effective method to manage anticoagulation
      therapy. This type of appointment is very convenient; it reduces travel and
      waiting times, costs, and potential no-show rates. OBJECTIVE: To assess changes
      in LDL-C levels from baseline to follow-up and number of patients attaining LDL-C
      goals during enrollment in the pharmacist-managed telephone lipid clinic (PMTLC).
      METHODS: A retrospective chart review was conducted on all patients enrolled in
      the clinic who had follow-up laboratory data available. Baseline LDL-C values
      were compared with values obtained at follow-up. Patients' total cholesterol
      (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) values
      were also collected and analyzed for improvement. The agents used, number of
      antidyslipidemic medications, and the incidence of adverse drug reactions prior
      to and during clinic enrollment were also collected. RESULTS: Patients in the
      PMTLC had a mean +/- SD reduction in LDL-C of 44.3 +/- 45.2 mg/dL (p < 0.001). In
      addition, 10 (28%) patients achieved the LDL-C goal (p = 0.002). Mean reductions
      in TC and TG levels were 44 mg/dL (18%) and 14.6 mg/dL (8%), respectively. There
      was no significant change in HDL-C levels. CONCLUSIONS: The PMTLC at the Erie,
      PA, Veterans Affairs Medical Center demonstrated statistically significant
      reduction in patients' LDL-C levels and increase in the number of patients
      attaining LDL-C goal.

PMID- 20028962
TI  - Two cases of sudden sensorineural hearing loss after methadone overdose.
AB  - OBJECTIVE: To document the presentation of 2 cases of sudden sensorineural
      hearing loss (SSHL) following methadone overdose. CASE SUMMARY: We report 2 cases
      of acute, bilateral methadone-induced hearing loss that took place on the same
      night in our emergency department. A 30-year-old male and his 25-year-old wife
      were found unresponsive in their home after ingesting an unknown, but presumably
      large, quantity of methadone. Drugs that are typically categorized as ototoxic
      were ruled out in each patient via rapid in-house urine drug screens as well with
      a comprehensive analysis via gas chromatography mass spectrometry. Methadone and
      tetrahydrocannabinol (THC) were the only drugs found in the toxicology screenings
      that were common to both patients. The man had a long treatment course that
      included several days in the intensive care unit. The woman recovered completely
      and was discharged within a day of admission. The hearing loss in both patients
      reversed completely within 24 hours. DISCUSSION: Several medications are commonly
      associated with ototoxicity, including nonsteroidal antiinflammatory drugs,
      antibiotics, loop diuretics, and chemotherapy agents. Although rare, drug-induced
      SSHL has been documented particularly among intravenous drug abusers after heroin
      injection. Until now, there has been only one published case report documenting
      drug-induced SSHL attributed to methadone. CONCLUSIONS: We believe methadone to
      be the probable cause of SSHL in both patients, because it and THC were the only
      common drugs found on toxicology screens, a recent case report involved methadone
      induced SSHL, and because of the suddenness of the onset and recovery of the
      patient's hearing coinciding with the time frame of the ingestion. The Naranjo
      probability scale score revealed that the adverse reaction was probable for each
      patient.

PMID- 20028964
TI  - Emerging role of neuregulin as a modulator of muscle metabolism.
AB  - Neuregulin was described initially as a neurotrophic factor involved in the
      formation of the neuromuscular junction in skeletal muscle. However, in recent
      years, neuregulin has been reported to be a myokine that exerts relevant effects
      on myogenesis and the regulation of muscle metabolism. In this new context, the
      rapid and chronic metabolic effects of neuregulin appear to be related to muscle
      contraction. Indeed, the effects of neuregulin resemble those of exercise, which
      are accompanied by an improvement in insulin sensitivity. In this review, we
      challenge the classical role assigned to neuregulin in muscle and propound the
      emerging concept of its involvement in the regulation of energetic metabolism and
      insulin responsiveness.

PMID- 20028965
TI  - Cardiomyocyte-derived adiponectin is biologically active in protecting against
      myocardial ischemia-reperfusion injury.
AB  - Adiponectin (APN) has traditionally been viewed as an adipocyte-specific
      endocrine molecule with cardioprotective effects. Recent studies suggest that APN
      is also expressed in cardiomyocytes. However, biological significances of this
      locally produced APN remain completely unknown. The aim of this study was to
      investigate the pathological and pharmacological significance of cardiac-derived
      APN in cardiomyocyte pathology. Adult cardiomyocytes from wild-type littermates
      (WT) or gene-deficient mice were pretreated with vehicle (V) or rosiglitazone
      (RSG) for 6 h followed by simulated ischemia-reperfusion (SI/R, 3 h/12 h).
      Compared with WT cardiomyocytes, myocytes from APN knockout (APN-KO) mice
      sustained greater SI/R injury, evidenced by greater oxidative/nitrative stress,
      caspase-3 activity, and lactate dehydrogenase (LDH) release (P < 0.05). Myocytes
      from adiponectin receptor 1 knockdown (AdipoR1-KD) or AdipoR1-KD/AdipoR2-KO mice
      had slightly increased SI/R injury, but the difference was not statistically
      significant. RSG significantly (P < 0.01) increased APN mRNA and protein
      expression, upregulated AdipoR1/AdipoR2 expression, reduced SI/R-induced
      apoptosis, and decreased LDH release in WT cardiomyocytes. However, the anti
      oxidative/anti-nitrative and cell protective effects of RSG were completely lost
      in APN-KO cardiomyocytes (P > 0.05 vs. vehicle group), although a comparable
      degree of AdipoR1/AdipoR2 upregulation was observed. The upregulatory effect of
      RSG on APN mRNA and protein expression was significantly potentiated in AdipoR1
      KD/AdipoR2-KO cardiomyocytes. However, the cellular protective effects of RSG
      were significantly blunted, although not completely lost, in these cells. These
      results demonstrated that cardiomyocyte APN is biologically active in protecting
      cells against SI/R injury. Moreover, this locally produced APN achieves its
      protective effect primarily through paracrine/autocrine activation of APN
      receptors.

PMID- 20028966
TI  - RAGE supports parathyroid hormone-induced gains in femoral trabecular bone.
AB  - Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but
      significant questions remain as to the underlying mechanisms. The receptor for
      advanced glycation end products (RAGE) is a multiligand receptor of the
      immunoglobulin superfamily; however, recent studies indicate a role in bone
      physiology. We investigated the significance of RAGE to hormone-induced increases
      in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice
      with human PTH-(1-34) at 30 microg.kg(-1).day(-1) or vehicle control, 7 days/wk,
      for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD)
      and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH
      mediated relative increases in cortical area of the midshaft femur were not
      compromised in the null mice. However, the hormone-induced gain in femoral
      cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE
      impaired PTH-mediated increases in femoral cancellous bone volume, connectivity
      density, and trabecular number but did not impact increases in trabecular
      thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral
      expression of bone formation genes, but their relative PTH-responsiveness was not
      impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response
      to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass,
      with the exception of the spine, and an enhanced accrual rate of fat mass. We
      conclude that RAGE is necessary for key aspects of the skeleton's response to
      anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of
      femoral trabecular architecture but not intrinsically necessary for increasing
      cortical thickness.

PMID- 20028967
TI  - Increased subsarcolemmal lipids in type 2 diabetes: effect of training on
      localization of lipids, mitochondria, and glycogen in sedentary human skeletal
      muscle.
AB  - The purpose of the study was to investigate the effect of aerobic training and
      type 2 diabetes on intramyocellular localization of lipids, mitochondria, and
      glycogen. Obese type 2 diabetic patients (n = 12) and matched obese controls (n =
      12) participated in aerobic cycling training for 10 wk. Endurance-trained
      athletes (n = 15) were included for comparison. Insulin action was determined by
      euglycemic-hyperinsulinemic clamp. Intramyocellular contents of lipids,
      mitochondria, and glycogen at different subcellular compartments were assessed by
      transmission electron microscopy in biopsies obtained from vastus lateralis
      muscle. Type 2 diabetic patients were more insulin resistant than obese controls
      and had threefold higher volume of subsarcolemmal (SS) lipids compared with obese
      controls and endurance-trained subjects. No difference was found in
      intermyofibrillar lipids. Importantly, following aerobic training, this excess SS
      lipid volume was lowered by approximately 50%, approaching the levels observed in
      the nondiabetic subjects. A strong inverse association between insulin
      sensitivity and SS lipid volume was found (r(2)=0.62, P = 0.002). The volume
      density and localization of mitochondria and glycogen were the same in type 2
      diabetic patients and control subjects, and showed in parallel with improved
      insulin sensitivity a similar increase in response to training, however, with a
      more pronounced increase in SS mitochondria and SS glycogen than in other
      localizations. In conclusion, this study, estimating intramyocellular
      localization of lipids, mitochondria, and glycogen, indicates that type 2
      diabetic patients may be exposed to increased levels of SS lipids. Thus
      consideration of cell compartmentation may advance the understanding of the role
      of lipids in muscle function and type 2 diabetes.

PMID- 20028968
TI  - Executioners of apoptosis in pancreatic {beta}-cells: not just for cell death.
AB  - Pancreatic beta-cell mass is dynamic and is regulated by beta-cell proliferation,
      neogenesis, and apoptosis. Under physiological conditions, apoptosis is tightly
      regulated with a slow, net rise in beta-cell mass over time. Excessive beta-cell
      apoptosis is an important contributor to both type 1 and type 2 diabetes
      development. Therefore, much effort has been given recently to better understand
      the mechanisms of apoptosis that occur both during physiological homeostasis and
      during the course of both types of diabetes. Caspases are the executioners of
      apoptosis that ultimately result in cell suicide. In mammals, there are 14
      caspases, of which many participate in the apoptotic pathways. Genetic mouse
      models have been important tools for elucidation of the specific apoptotic
      pathways that play an essential role in beta-cell apoptosis under physiological
      and pathological conditions. This review focuses on the diverse roles of each of
      the specific caspases and their regulators, unveiling both the classical
      apoptotic roles as well as emerging nonapoptotic roles.

PMID- 20028969
TI  - Metabolic effects of intensive insulin therapy in critically ill patients.
AB  - Our aim was to investigate the effects of glycemic control and insulin
      concentration on lipolysis, glucose, and protein metabolism in critically ill
      medical patients. For our methods, the patients were studied twice. In study 1,
      blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with
      intravenous insulin. After study 1, patients entered one of four protocols for 48
      h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9
      mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high
      insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin
      requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG;
      insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6
      mmol/l]. Age-matched healthy control subjects received two-step euglycemic
      hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups.
      In our results, whole body proteolysis was higher in patients in study 1 (P <
      0.006) compared with control subjects at comparable insulin concentrations and
      was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in
      patients. Endogenous glucose production rate (R(a)), glucose disposal, and
      lipolysis were not different in all patients in study 1 compared with control
      subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not
      change in any of the study 2 patient groups. HI increased glucose disposal in the
      patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in
      controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin
      administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis
      and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia
      nor normoglycemia had any protein-sparing effect.

PMID- 20028970
TI  - Identification of clusterin domain involved in NF-kappaB pathway regulation.
AB  - Clusterin (CLU) is a ubiquitous protein that has been implicated in
      tumorigenesis, apoptosis, inflammation, and cell proliferation. We and others
      have previously shown that CLU is an inhibitor of the NF-kappaB pathway. However,
      the exact form of CLU and the region(s) of CLU involved in this effect were
      unknown. Using newly generated molecular constructs encoding for CLU and various
      regions of the molecule, we demonstrated that the presecretory form of CLU
      (psCLU) form bears the NF-kappaB regulatory activity. Sequence comparison
      analysis showed sequence motif identity between CLU and beta-transducin repeat
      containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB
      alpha degradation. These homologies were localized in the disulfide constraint
      region of CLU. We generated a specific molecular construct of this region, named
      DeltaCLU, and showed that it has the same NF-kappaB regulatory activity as CLU.
      Neither the alpha-chain nor the beta-chain of CLU had any NF-kappaB regulatory
      activity. Furthermore, we showed that following tumor necrosis factor-alpha
      stimulation of transfected cells, we could co-immunoprecipitate phospho-IkappaB
      alpha with DeltaCLU. Moreover, we showed that DeltaCLU could localize both in the
      cytoplasm and in the nucleus. These results demonstrate the identification of a
      new CLU activity site involved in NF-kappaB pathway regulation.

PMID- 20028971
TI  - c-Jun N-terminal kinase enhances MST1-mediated pro-apoptotic signaling through
      phosphorylation at serine 82.
AB  - Protein kinases play an important role in the maintenance of homeostasis between
      cell survival and apoptosis. Deregulation of these kinases leads to various
      pathological manifestations, such as cancer and neurodegenerative diseases. The
      MST1 encodes a serine/threonine kinase that is activated upon apoptotic
      stimulation, which in turn phosphorylates its downstream targets, Histone H2B and
      FOXO. However, the upstream regulators of MST1 kinase have been poorly studied.
      In this study, we report that JNK (c-Jun N-terminal kinase) phosphorylates MST1
      at serine 82, which leads to the enhancement of MST1 activation. Accordingly, the
      activation of MST1 phosphorylates FOXO3 at serine 207 and promotes cell death.
      The inhibition of JNK kinase per se attenuates MST1 activity and nuclear
      translocation as well as MST1-induced apoptosis. We also find the S82A (serine
      mutated to alanine) diminishes MST1 activation and its effect on the FOXO
      transcription activity. Collectively, these findings define the novel feedback
      regulation of MST1 kinase activation by its putative substrate, JNK, with
      implication for our understanding of the signaling mechanism during cell death.

PMID- 20028972
TI  - STAT5 activation is critical for the transformation mediated by
      myeloproliferative disorder-associated JAK2 V617F mutant.
AB  - It has been well established that disruption of JAK2 signaling regulation is
      involved in various hematopoietic disorders; however, the detailed mechanism by
      which abnormal activation of JAK2 exhibits transforming activity remains to be
      elucidated. Here, to clarify the functional role of the erythropoietin receptor
      (EpoR) and its downstream transcription factor STAT5 in the abnormal activation
      of JAK2-induced hematopoietic diseases, we generated a stable transfectant of
      Ba/F3 cells expressing EpoR and analyzed the molecular mechanism of how JAK2
      mutation induces cell growth disorder. JAK2 V617F mutant exhibited transforming
      activity when EpoR was coexpressed. According to a study utilizing several
      truncated mutants of EpoR, the ability of EpoR to facilitate the transforming
      activity of JAK2 V617F mutant required the intracellular domain to interact with
      STAT5. Strikingly, once the truncated EpoR (EpoR-H) was mutated on Tyr-343, the
      phosphorylation of which is known to be important for interaction with STAT5,
      JAK2 V617F mutant failed to exhibit transforming activity, suggesting that STAT5
      is critical for JAK2 mutant-induced hematopoietic disorder. Furthermore, the
      expression of the constitutively active STAT5 mutant exhibited transforming
      activity in Ba/F3 cells, and short hairpin RNA-mediated knockdown of STAT5
      significantly inhibited the transforming activity of JAK2 V617F mutant. Taking
      these observations together, STAT5 plays an essential role in EpoR-JAK2 V617F
      mutant-induced hematopoietic disorder. Although it remains unclear why the
      presence of EpoR is required to activate oncogenic signaling via the JAK2 mutant
      and STAT5, its interacting ability is a target for the treatment of these
      hematopoietic diseases.

PMID- 20028973
TI  - Initiation factor eIF2-independent mode of c-Src mRNA translation occurs via an
      internal ribosome entry site.
AB  - Overexpression and activation of the c-Src protein have been linked to the
      development of a wide variety of cancers. The molecular mechanism(s) of c-Src
      overexpression in cancer cells is not clear. We report here an internal ribosome
      entry site (IRES) in the c-Src mRNA that is constituted by both 5'-noncoding and 
      coding regions. The inhibition of cap-dependent translation by m(7)GDP in the
      cell-free translation system or induction of endoplasmic reticulum stress in
      hepatoma-derived cells resulted in stimulation of the c-Src IRES activities.
      Sucrose density gradient analyses revealed formation of a stable binary complex
      between the c-Src IRES and purified HeLa 40 S ribosomal subunit in the absence of
      initiation factors. We further demonstrate eIF2-independent assembly of 80 S
      initiation complex on the c-Src IRES. These features of the c-Src IRES appear to
      be reminiscent of that of hepatitis C virus-like IRESs and translation initiation
      in prokaryotes. Transfection studies and genetic analysis revealed that the c-Src
      IRES permitted initiation at the authentic AUG351, which is also used for
      conventional translation initiation of the c-Src mRNA. Our studies unveiled a
      novel regulatory mechanism of c-Src synthesis mediated by an IRES element, which
      exhibits enhanced activity during cellular stress and is likely to cause c-Src
      overexpression during oncogenesis and metastasis.

PMID- 20028974
TI  - Thermodynamic analysis of the CSL x Notch interaction: distribution of binding
      energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of
      competition with the viral transactivator EBNA2.
AB  - The Notch signaling pathway is a cell-cell communication network giving rise to
      cell differentiation during metazoan development. Activation of the pathway
      releases the intracellular portion of the Notch receptor to translocate to the
      nucleus, where it is able to interact with the effector transcription factor CSL,
      converting CSL from a transcriptional repressor to an activator. This conversion
      is dependent upon the high affinity binding of the RAM region of the Notch
      receptor to the beta-trefoil domain (BTD) of CSL. Here we probe the energetics of
      binding to BTD of each conserved residue of RAM through the use of isothermal
      titration calorimetry and single residue substitution. We find that although the
      highly conserved PhiW PhiP motif is the largest determinant of binding,
      energetically significant interactions are contributed by N-terminal residues,
      including a conserved Arg/Lys-rich region. Additionally, we present a
      thermodynamic analysis of the interaction between the Epstein-Barr virus protein
      EBNA2 with BTD and explore the extent to which the EBNA2- and RAM-binding sites
      on BTD are nonoverlapping, as proposed by Fuchs et al. (Fuchs, K. P., Bommer, G.,
      Dumont, E., Christoph, B., Vidal, M., Kremmer, E., and Kempkes, B. (2001) Eur. J.
      Biochem. 268, 4639-4646). Combining these results with displacement isothermal
      titration calorimetry, we propose a mechanism by which the PhiW PhiP motif of RAM
      and EBNA2 compete with one another for binding at the hydrophobic pocket of BTD
      using overlapping but specific interactions that are unique to each BTD ligand.

PMID- 20028975
TI  - Differential phosphorylation of RhoGDI mediates the distinct cycling of Cdc42 and
      Rac1 to regulate second-phase insulin secretion.
AB  - Cdc42 cycling through GTP/GDP states is critical for its function in the
      second/granule mobilization phase of insulin granule exocytosis in pancreatic
      islet beta cells, although the identities of the Cdc42 cycling proteins involved
      remain incomplete. Using a tandem affinity purification-based mass spectrometry
      screen for Cdc42 cycling factors in beta cells, RhoGDI was identified. RNA
      interference-mediated depletion of RhoGDI from isolated islets selectively
      amplified the second phase of insulin release, consistent with the role of RhoGDI
      as a Cdc42 cycling factor. Replenishment of RhoGDI to RNA interference-depleted
      cells normalized secretion, confirming the action of RhoGDI to be that of a
      negative regulator of Cdc42 activation. Given that RhoGDI also regulates Rac1
      activation in beta cells, and that Rac1 activation occurs in a Cdc42-dependent
      manner, the question as to how the beta cell utilized RhoGDI for differential
      Cdc42 and Rac1 cycling was explored. Co-immunoprecipitation was used to determine
      that RhoGDI-Cdc42 complexes dissociated upon stimulation of beta cells with
      glucose for 3 min, correlating with the timing of glucose-induced Cdc42
      activation and the onset of RhoGDI tyrosine phosphorylation. Glucose-induced
      disruption of RhoGDI-Rac1 complexes occurred subsequent to this, coincident with
      Rac1 activation, which followed the onset of RhoGDI serine phosphorylation.
      RhoGDI-Cdc42 complex dissociation was blocked by mutation of RhoGDI residue Tyr
      156, whereas RhoGDI-Rac1 dissociation was blocked by RhoGDI mutations Y156F and
      S101A/S174A. Finally, expression of a triple Y156F/S101A/S174A-RhoGDI mutant
      specifically inhibited only the second/granule mobilization phase of glucose
      stimulated insulin secretion, overall supporting the integration of RhoGDI into
      the activation cycling mechanism of glucose-responsive small GTPases.

PMID- 20028976
TI  - Targets of the Tal1 transcription factor in erythrocytes: E2 ubiquitin conjugase
      regulation by Tal1.
AB  - The Tal1 transcription factor is essential for the development of the
      hematopoietic system and plays a role during definitive erythropoiesis in the
      adult. Despite the importance of Tal1 in erythropoiesis, only a small number of
      erythroid differentiation target genes are known. A chromatin precipitation and
      cloning approach was established to uncover novel Tal1 target genes in
      erythropoiesis. The BirA tag/BirA ligase biotinylation system in combination with
      streptavidin chromatin precipitation (Strep-CP) was used to co-precipitate
      genomic DNA bound to Tal1. Tal1 was found to bind in the vicinity of 31 genes
      including the E2-ubiquitin conjugase UBE2H gene. Binding of Tal1 to UBE2H was
      confirmed by chromatin immunoprecipitation. UBE2H expression is increased during
      erythroid differentiation of hCD34(+) cells. Tal1 expression activated UBE2H
      expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin
      transfer activity. This study identifies parts of the ubiquitinylation machinery
      as a cellular target downstream of the transcription factor Tal1 and provides
      novel insights into Tal1-regulated erythropoiesis.

PMID- 20028977
TI  - Adiponectin promotes macrophage polarization toward an anti-inflammatory
      phenotype.
AB  - It is established that the adipocyte-derived cytokine adiponectin protects
      against cardiovascular and metabolic diseases, but the effect of this adipokine
      on macrophage polarization, an important mediator of disease progression, has
      never been assessed. We hypothesized that adiponectin modulates macrophage
      polarization from that resembling a classically activated M1 phenotype to that
      resembling alternatively-activated M2 cells. Peritoneal macrophages and the
      stromal vascular fraction (SVF) cells of adipose tissue isolated from adiponectin
      knock-out mice displayed increased M1 markers, including tumor necrosis factor
      alpha, interleukin-6, and monocyte chemoattractant protein-1 and decreased M2
      markers, including arginase-1, macrophage galactose N-acetyl-galactosamine
      specific lectin-1, and interleukin-10. The systemic delivery of adenovirus
      expressing adiponectin significantly augmented arginase-1 expression in
      peritoneal macrophages and SVF cells in both wild-type and adiponectin knock-out
      mice. In culture, the treatment of macrophages with recombinant adiponectin
      protein led to an increase in the levels of M2 markers and a reduction of
      reactive oxygen species and reactive oxygen species-related gene expression.
      Adiponectin also stimulated the expression of M2 markers and attenuated the
      expression of M1 markers in human monocyte-derived macrophages and SVF cells
      isolated from human adipose tissue. These data show that adiponectin functions as
      a regulator of macrophage polarization, and they indicate that conditions of high
      adiponectin expression may deter metabolic and cardiovascular disease progression
      by favoring an anti-inflammatory phenotype in macrophages.

PMID- 20028978
TI  - Mycobacterium tuberculosis cAMP receptor protein (Rv3676) differs from the
      Escherichia coli paradigm in its cAMP binding and DNA binding properties and
      transcription activation properties.
AB  - The pathogen Mycobacterium tuberculosis produces a burst of cAMP upon infection
      of macrophages. Bacterial cyclic AMP receptor proteins (CRP) are transcription
      factors that respond to cAMP by binding at target promoters when cAMP
      concentrations increase. Rv3676 (CRP(Mt)) is a CRP family protein that regulates
      expression of genes (rpfA and whiB1) that are potentially involved in M.
      tuberculosis persistence and/or emergence from the dormant state. Here, the
      CRP(Mt) homodimer is shown to bind two molecules of cAMP (one per protomer) at
      noninteracting sites. Furthermore, cAMP binding by CRP(Mt) was relatively weak,
      entropy driven, and resulted in a relatively small enhancement in DNA binding.
      Tandem CRP(Mt)-binding sites (CRP1 at -58.5 and CRP2 at -37.5) were identified at
      the whiB1 promoter (PwhiB1). In vitro transcription reactions showed that CRP1 is
      an activating site and that CRP2, which was only occupied in the presence of cAMP
      or at high CRP(Mt) concentrations in the absence of cAMP, is a repressing site.
      Binding of CRP(Mt) to CRP1 was not essential for open complex formation but was
      required for transcription activation. Thus, these data suggest that binding of
      CRP(Mt) to the PwhiB1 CRP1 site activates transcription at a step after open
      complex formation. In contrast, high cAMP concentrations allowed occupation of
      both CRP1 and CRP2 sites, resulting in inhibition of open complex formation.
      Thus, M. tuberculosis CRP has evolved several distinct characteristics, compared
      with the Escherichia coli CRP paradigm, to allow it to regulate gene expression
      against a background of high concentrations of cAMP.

PMID- 20028979
TI  - Activation of the Ran GTPase is subject to growth factor regulation and can give
      rise to cellular transformation.
AB  - Although the small GTPase Ran is best known for its roles in nucleocytoplasmic
      transport, mitotic spindle assembly, and nuclear envelope formation, recent
      studies have demonstrated the overexpression of Ran in multiple tumor types and
      that its expression is correlated with a poor patient prognosis, providing
      evidence for the importance of this GTPase in cell growth regulation. Here we
      show that Ran is subject to growth factor regulation by demonstrating that it is
      activated in a serum-dependent manner in human breast cancer cells and, in
      particular, in response to heregulin, a growth factor that activates the
      Neu/ErbB2 tyrosine kinase. The heregulin-dependent activation of Ran requires
      mTOR (mammalian target of rapamycin) and stimulates the capped RNA binding
      capability of the cap-binding complex in the nucleus, thus influencing gene
      expression at the level of mRNA processing. We further demonstrate that the
      excessive activation of Ran has important consequences for cell growth by showing
      that a novel, activated Ran mutant is sufficient to transform NIH-3T3 cells in an
      mTOR- and epidermal growth factor receptor-dependent manner and that Ran
      transformed cells form tumors in mice.

PMID- 20028980
TI  - Inhibition of AcpA phosphatase activity with ascorbate attenuates Francisella
      tularensis intramacrophage survival.
AB  - Acid phosphatase activity in the highly infectious intracellular pathogen
      Francisella tularensis is directly related with the ability of these bacteria to
      survive inside host cells. Pharmacological inactivation of acid phosphatases
      could potentially help in the treatment of tularemia or even be utilized to
      neutralize the infection. In the present work, we report inhibitory compounds for
      three of the four major acid phosphatases produced by F. tularensis SCHU4: AcpA,
      AcpB, and AcpC. The inhibitors were identified using a catalytic screen from a
      library of chemicals approved for use in humans. The best results were obtained
      against AcpA. The two compounds identified, ascorbate (K(i) = 380 +/- 160 microM)
      and 2-phosphoascorbate (K(i) = 3.2 +/- 0.85 microM) inhibit AcpA in a
      noncompetitive, nonreversible fashion. A potential ascorbylation site in the
      proximity of the catalytic pocket of AcpA was identified using site-directed
      mutagenesis. The effects of the inhibitors identified in vitro were evaluated
      using bioassays determining the ability of F. tularensis to survive inside
      infected cells. The presence of ascorbate or 2-phosphoascorbate impaired the
      intramacrophage survival of F. tularensis in an AcpA-dependent manner as it was
      probed using knockout strains. The evidence presented herein indicated that
      ascorbate could be a good alternative to be used clinically to improve treatments
      against tularemia.

PMID- 20028981
TI  - Ran overexpression leads to diminished T cell responses and selectively modulates
      nuclear levels of c-Jun and c-Fos.
AB  - Ras-related nuclear protein (Ran) is a Ras family GTPase, and its documented
      functions are the regulation of DNA replication, cell cycle progression, nuclear
      structure formation, RNA processing and exportation, and nuclear protein
      importation. In this study, we performed detailed mapping of Ran expression
      during mouse ontogeny using in situ hybridization. High Ran expression was found
      in various organs and tissues including the thymus cortex and spleen white pulp.
      Ran was induced in T cells 24 h after their activation. The function of Ran in
      the immune system was investigated using Ran transgenic (Tg) mice. In Ran Tg T
      cells, there was compromised activation marker expression, lymphokine secretion,
      and proliferation upon T cell receptor activation in vitro when compared with
      wild type T cells. Tg mice also manifested defective delayed type
      hypersensitivity in vivo. Upon PMA and ionomycin stimulation, Tg T cells were
      defective in nuclear accumulation of AP-1 factors (c-Jun and c-Fos) but not NF
      kappaB family members. Our experiments showed that Ran had important regulatory
      function in T cell activation. One of the possible mechanisms is that
      intracellular Ran protein levels control the nuclear retention for selective
      transcription factors such as c-Jun and c-Fos of AP-1, which is known to be
      critical in T cell activation and proliferation and lymphokine secretion.

PMID- 20028982
TI  - Interaction between Hhex and SOX13 modulates Wnt/TCF activity.
AB  - Fine-tuning of the Wnt/TCF pathway is crucial for multiple embryological
      processes, including liver development. Here we describe how the interaction
      between Hhex (hematopoietically expressed homeobox) and SOX13 (SRY-related high
      mobility group box transcription factor 13), modulates Wnt/TCF pathway activity.
      Hhex is a homeodomain factor expressed in multiple endoderm-derived tissues, like
      the liver, where it is essential for proper development. The pleiotropic
      expression of Hhex during embryonic development and its dual role as a
      transcriptional repressor and activator suggest the presence of different tissue
      specific partners capable of modulating its activity and function. While
      searching for developmentally regulated Hhex partners, we set up a yeast two
      hybrid screening using an E9.5-10.5 mouse embryo library and the N-terminal
      domain of Hhex as bait. Among the putative protein interactors, we selected SOX13
      for further characterization. We found that SOX13 interacts directly with full
      length Hhex, and we delineated the interaction domains within the two proteins.
      SOX13 is known to repress Wnt/TCF signaling by interacting with TCF1. We show
      that Hhex is able to block the SOX13-dependent repression of Wnt/TCF activity by
      displacing SOX13 from the SOX13 x TCF1 complex. Moreover, Hhex de-repressed the
      Wnt/TCF pathway in the ventral foregut endoderm of cultured mouse embryos
      electroporated with a SOX13-expressing plasmid. We conclude that the interaction
      between Hhex and SOX13 may contribute to control Wnt/TCF signaling in the early
      embryo.

PMID- 20028983
TI  - Native-unlike long-lived intermediates along the folding pathway of the
      amyloidogenic protein beta2-microglobulin revealed by real-time two-dimensional
      NMR.
AB  - Beta2-microglobulin (beta2m), the light chain of class I major histocompatibility
      complex, is responsible for the dialysis-related amyloidosis and, in patients
      undergoing long term dialysis, the full-length and chemically unmodified beta2m
      converts into amyloid fibrils. The protein, belonging to the immunoglobulin
      superfamily, in common to other members of this family, experiences during its
      folding a long-lived intermediate associated to the trans-to-cis isomerization of
      Pro-32 that has been addressed as the precursor of the amyloid fibril formation.
      In this respect, previous studies on the W60G beta2m mutant, showing that the
      lack of Trp-60 prevents fibril formation in mild aggregating condition, prompted
      us to reinvestigate the refolding kinetics of wild type and W60G beta2m at atomic
      resolution by real-time NMR. The analysis, conducted at ambient temperature by
      the band selective flip angle short transient real-time two-dimensional NMR
      techniques and probing the beta2m states every 15 s, revealed a more complex
      folding energy landscape than previously reported for wild type beta2m, involving
      more than a single intermediate species, and shedding new light into the
      fibrillogenic pathway. Moreover, a significant difference in the kinetic scheme
      previously characterized by optical spectroscopic methods was discovered for the
      W60G beta2m mutant.

PMID- 20028984
TI  - Human negative elongation factor activates transcription and regulates
      alternative transcription initiation.
AB  - The human negative elongation factor (NELF) is a four-subunit protein complex
      that inhibits the movement of RNA polymerase II (RNAPII) at an early elongation
      stage in vitro. NELF-mediated stalling of RNAPII also attenuates transcription of
      a number of inducible genes in human cells. To obtain a genome-wide understanding
      of human NELF-mediated transcriptional regulation in vivo, we carried out an exon
      array study in T47D breast cancer cells with transient small interfering RNA
      knockdown of individual NELF subunits. Upon depletion of NELF-A, -C, or -E, the
      vast majority of NELF-regulated genes were down-regulated. Many of the down
      regulated genes encode proteins that play key roles in cell cycle progression.
      Consequently, NELF knockdown resulted in significant reduction in DNA synthesis
      and cell proliferation. Chromatin immunoprecipitation showed that NELF knockdown
      led to dissociation of RNAPII from the promoter-proximal region of the cell cycle
      regulating genes. This was accompanied by decreased histone modifications
      associated with active transcription initiation (H3K9Ac) and elongation
      (H3K36Me3), as well as reduced recruitment of the general transcription factor
      TFIIB and increased overall histone occupancy at a subset of the down-regulated
      promoters. Lastly, our study indicates that NELF regulates alternative
      transcription initiation of BSG (Basigin) gene by differentially influencing
      RNAPII density at the two neighboring exons at the 5' end of the gene. Taken
      together, our data suggest a diverse transcriptional consequence of NELF-mediated
      RNAPII pausing in the human genome.

PMID- 20028985
TI  - Reduction of Raf kinase inhibitor protein expression by Bcr-Abl contributes to
      chronic myelogenous leukemia proliferation.
AB  - Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal
      translocation (9;22) that generates the Bcr-Abl fusion gene. The Ras/Raf
      1/MEK/ERK pathway is constitutively activated in Bcr-Abl-transformed cells, and
      Ras activity enhances the oncogenic ability of Bcr-Abl. However, the mechanism by
      which Bcr-Abl activates the Ras pathway is not completely understood. Raf kinase
      inhibitor protein (RKIP) inhibits activation of MEK by Raf-1 and its downstream
      signal transduction, resulting in blocking the MAP kinase pathway. In the present
      study, we found that RKIP was depleted in CML cells. We investigated the
      interaction between RKIP and Bcr-Abl in CML cell lines and Bcr-Abl(+) progenitor
      cells from CML patients. The Abl kinase inhibitors and depletion of Bcr-Abl
      induced the expression of RKIP and reduced the pERK1/2 status, resulting in
      inhibited proliferation of CML cells. Moreover, RKIP up-regulated cell cycle
      regulator FoxM1 expression, resulting in G(1) arrest via p27(Kip1) and p21(Cip1)
      accumulation. In colony-forming unit granulocyte, erythroid, macrophage,
      megakaryocyte, colony-forming unit-granulocyte macrophage, and burst-forming unit
      erythroid, treatment with the Abl kinase inhibitors and depletion of Bcr-Abl
      induced RKIP and reduced FoxM1 expressions, and inhibited colony formation of Bcr
      Abl(+) progenitor cells, whereas depletion of RKIP weakened the inhibition of
      colony formation activity by the Abl kinase inhibitors in Bcr-Abl(+) progenitor
      cells. Thus, Bcr-Abl represses the expression of RKIP, continuously activates
      pERK1/2, and suppresses FoxM1 expression, resulting in proliferation of CML
      cells.

PMID- 20028986
TI  - Phosphorylation-dependent activation of peroxisome proliferator protein PEX11
      controls peroxisome abundance.
AB  - Peroxisomes are dynamic organelles that divide continuously in growing cell
      cultures and expand extensively in lipid-rich medium. Peroxisome population
      control is achieved in part by Pex11p-dependent regulation of peroxisome size and
      number. Although the production of Pex11p in yeast is tightly linked to
      peroxisome biogenesis by transcriptional regulation of the PEX11 gene, it remains
      unclear if and how Pex11p activity could be modulated by rapid signaling. We
      report the reversible phosphorylation of Saccharomyces cerevisiae Pex11p in
      response to nutritional cues and delineate a mechanism for phosphorylation
      dependent activation of Pex11p through the analysis of phosphomimicking mutants.
      Peroxisomal phenotypes in the PEX11-A and PEX11-D strains expressing
      constitutively dephosphorylated and phosphorylated forms of Pex11p resemble those
      of PEX11 gene knock-out and overexpression mutants, although PEX11 transcript and
      Pex11 protein levels remain unchanged. We demonstrate functional inequality and
      differences in subcellular localization of the Pex11p forms. Pex11Dp promotes
      peroxisome fragmentation when reexpressed in cells containing induced
      peroxisomes. Pex11p translocates between endoplasmic reticulum and peroxisomes in
      a phosphorylation-dependent manner, whereas Pex11Ap and Pex11Dp are impaired in
      trafficking and constitutively associated with mature and proliferating
      peroxisomes, respectively. Overexpression of cyclin-dependent kinase Pho85p
      results in hyperphosphorylation of Pex11p and peroxisome proliferation. This
      study provides the first evidence for control of peroxisome dynamics by
      phosphorylation-dependent regulation of a peroxin.

PMID- 20028987
TI  - Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation
      of epididymally derived white adipocyte cultures reveals a population of
      thermogenically competent, UCP1-containing adipocytes molecularly distinct from
      classic brown adipocytes.
AB  - The recent insight that brown adipocytes and muscle cells share a common origin
      and in this respect are distinct from white adipocytes has spurred questions
      concerning the origin and molecular characteristics of the UCP1-expressing cells
      observed in classic white adipose tissue depots under certain physiological or
      pharmacological conditions. Examining precursors from the purest white adipose
      tissue depot (epididymal), we report here that chronic treatment with the
      peroxisome proliferator-activated receptor gamma agonist rosiglitazone promotes
      not only the expression of PGC-1alpha and mitochondriogenesis in these cells but
      also a norepinephrine-augmentable UCP1 gene expression in a significant subset of
      the cells, providing these cells with a genuine thermogenic capacity. However,
      although functional thermogenic genes are expressed, the cells are devoid of
      transcripts for the novel transcription factors now associated with classic brown
      adipocytes (Zic1, Lhx8, Meox2, and characteristically PRDM16) or for myocyte
      associated genes (myogenin and myomirs (muscle-specific microRNAs)) and retain
      white fat characteristics such as Hoxc9 expression. Co-culture experiments verify
      that the UCP1-expressing cells are not proliferating classic brown adipocytes
      (adipomyocytes), and these cells therefore constitute a subset of adipocytes
      ("brite" adipocytes) with a developmental origin and molecular characteristics
      distinguishing them as a separate class of cells.

PMID- 20028992
TI  - Useful immunohistochemical markers of tumor differentiation.
AB  - Immunohistochemistry (IHC) has been somewhat underutilized in the practice of
      toxicological pathology but can be a valuable tool for the evaluation of rodent
      neoplasms, both in a diagnostic and an investigational role. Determining an exact
      tumor type using standard hematoxylin and eosin (H&E) staining of formalin-fixed
      tissues can be challenging, especially with metastatic and/or poorly
      differentiated tumors. Successful IHC is dependent on many factors, including
      species and tissue type, type and duration of fixation, quality fresh or frozen
      sectioning, and antibody specificity. The initial approach of most tumor
      diagnosis IHC applications is distinguishing epithelial from mesenchymal
      differentiation using vimentin and cytokeratin markers, although false-negative
      and/or false-positive results may occur. Experimentally, IHC can be employed to
      investigate the earliest changes in transformed tissues, identifying cellular
      changes not normally visible with H&E. Individual markers for proliferation,
      apoptosis, and specific tumor proteins can be used to help distinguish
      hyperplasia from neoplasia and determine specific tumor origin/type. IHC provides
      a relatively rapid and simple method to better determine the origin of neoplastic
      tissue or investigate the behavior or progression of a given neoplasm. Several
      experimental and diagnostic examples will be presented to illustrate the utility
      of IHC as a supplement to standard staining techniques.

PMID- 20028994
TI  - The strategic health authorities' emergency services review.

PMID- 20028995
TI  - The service concept: the missing link in our specialty's development?

PMID- 20028993
TI  - Risks of Lynch syndrome cancers for MSH6 mutation carriers.
AB  - BACKGROUND: Germline mutations in MSH6 account for 10%-20% of Lynch syndrome
      colorectal cancers caused by hereditary DNA mismatch repair gene mutations.
      Because there have been only a few studies of mutation carriers, their cancer
      risks are uncertain. METHODS: We identified 113 families of MSH6 mutation
      carriers from five countries that we ascertained through family cancer clinics
      and population-based cancer registries. Mutation status, sex, age, and histories
      of cancer, polypectomy, and hysterectomy were sought from 3104 of their
      relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for
      cancer risks of carriers, compared with those of the general population of the
      same country, were estimated by use of a modified segregation analysis with
      appropriate conditioning depending on ascertainment. RESULTS: For MSH6 mutation
      carriers, the estimated cumulative risks to ages 70 and 80 years, respectively,
      were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14%
      to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and
      20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to
      36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch
      syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40%
      (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with
      incidence for the general population, MSH6 mutation carriers had an eightfold
      increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which
      was independent of sex and age. Women who were MSH6 mutation carriers had a 26
      fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7)
      and a sixfold increased incidence of other cancers associated with Lynch syndrome
      (HR = 6.0, 95% CI = 3.4 to 10.7). CONCLUSION: We have obtained precise and
      accurate estimates of both absolute and relative cancer risks for MSH6 mutation
      carriers.

PMID- 20028996
TI  - Performance of influenza rapid antigen testing in influenza in emergency
      department patients.
AB  - BACKGROUND: The use of rapid antigen tests to triage specimens for polymerase
      chain reaction (PCR) testing from emergency department patients with influenza
      like illness during surveillance for novel influenza viruses has been suggested.
      OBJECTIVE: To measure the observed sensitivity and specificity for a widely used
      rapid antigen test (Binax) using a PCR-based assay (Medical Diagnostic
      Laboratories). METHODS: Nasopharyngeal samples were taken with flocked swabs
      (Copan Diagnostics) from patients presenting to the emergency department of a
      community hospital. Samples were analysed using a rapid antigen and a PCR-based
      test. PCR testing was used as the criterion reference. Sensitivity and
      specificity were calculated for influenza and influenza A. Positive predictive
      values were calculated over a range of possible prevalence. RESULTS: Samples from
      566 unique patients were tested using both methods. Sensitivity was 69.1% (95% CI
      58.9% to 78.1%) and specificity was 97.7% (95% CI 95.8% to 98.8%) for the
      detection of any influenza and 75.3% (95% CI 64.7% to 84.0%) and 97.8% (95% CI
      95.9% to 98.9%), respectively, for influenza A only. The resultant positive
      predictive value ranges from 23% to 77% when the prevalence ranges from 1% to
      10%. CONCLUSION: When planning early outbreak surveillance, provision of adequate
      PCR testing capacity rather than triaging specimens using rapid antigen testing
      for influenza is advisable.

PMID- 20028997
TI  - Sustained manual abdominal compression during cardiopulmonary resuscitation in a
      pig model: a preliminary investigation.
AB  - OBJECTIVES: The present study was undertaken to determine whether sustained
      manual abdominal compression (SMAC) using left paramedian compression technique
      can improve coronary perfusion pressure (CPP) during cardiopulmonary
      resuscitation (CPR) and resuscitation outcomes without causing liver laceration.
      METHODS: Ventricular fibrillation was induced in 14 pigs, and circulatory arrest
      was maintained for 6 min. Animals were resuscitated either by standard CPR
      (control group) or by standard CPR with SMAC (SMAC-CPR group). RESULTS: Mean
      blood pressure, aortic diastolic pressure and right atrial diastolic pressure in
      the SMAC-CPR group were significantly greater than in the control group
      throughout simulated basic life support. However, since the increases in aortic
      and right atrial diastolic pressures were similar, no significant intergroup
      difference was found in terms of CPP. Return of spontaneous circulation (ROSC)
      was attained in four of seven animals in the control group and in six of seven
      animals in the SMAC-CPR group (p = 0.55). Three animals in the control group and
      four in the SMAC-CPR group survived 24 h after ROSC (p = 1.00). Two of the seven
      animals in the SMAC-CPR group had a ruptured liver, but no such injury occurred
      in the control group. CONCLUSIONS: SMAC using left paramedian compression
      technique failed to improve CPP during CPR and resuscitation outcomes.
      Furthermore, this method could not avoid liver laceration.

PMID- 20028998
TI  - Comparison of four manikins and fresh frozen cadaver models for direct
      laryngoscopic orotracheal intubation training.
AB  - OBJECTIVE: To compare the acceptability and preference between manikin models and
      fresh frozen cadaver (FFC) for direct laryngoscopic orotracheal intubation
      training. METHODS: In this prospective crossover trial, participants in the
      airway workshop performed direct laryngoscopic orotracheal intubation on four
      airway training manikins: Airway Management Trainer (Ambu, St Ives, UK), Airway
      Trainer (Laerdal, Medical, Stavanger, Norway), Airsim (Trucorp, Belfast, Northern
      Ireland) and "Bill 1" (VBM, Sulz, Germany), and FFC. Participants were asked to
      access the following: reality of jaw mobility, difficulty with mouth opening,
      reality of neck flexibility, difficulty with intubation, overall model reality
      and model preference for each model using a visual analogue scale (VAS) of 0-10
      cm. The VAS scores for each model were compared. RESULTS: Fifty-six participants
      were included in the study. The FFC had a highest VAS score for reality of jaw
      mobility, overall reality and preference of model. Trucorp manikin and Laerdal
      manikin followed cadaver. There were no significant statistical differences
      between Trucorp manikin and Laerdal manikin. In difficulty with mouth opening and
      difficulty with intubation, Trucorp manikin had the lowest VAS score. CONCLUSION:
      The FFC is a more realistic and preferred model for direct laryngoscopic
      orotracheal intubation training. Trucorp and Laerdal manikin can be used as
      alternative models.

PMID- 20028999
TI  - An intervention trial increases the evidence-based use of bupivacaine in hand
      injuries.
AB  - AIM: Published evidence indicates that bupivacaine is the superior local
      anaesthetic for digital nerve blocks and where long-lasting analgesia is
      desirable. We aimed to develop and evaluate a multifaceted education initiative
      designed to improve the evidence-based use of bupivacaine in hand injuries.
      METHODS: This was a pre- and post-intervention trial undertaken in a single
      emergency department (ED). All physicians working in the ED were included. The
      intervention comprised a specifically designed "e-learning module" supplemented
      by in-service training, reminder techniques and improved accessibility to
      bupivacaine. The primary end point was the proportion of patients with hand
      injuries administered bupivacaine in whom bupivacaine was the most appropriate
      local anaesthetic. Data were collected by explicit chart review of consecutive
      cases. RESULTS: Both pre- and post-intervention periods were of 5 months'
      duration. The charts of 107 pre-intervention and 111 post-intervention cases were
      reviewed. In the post-intervention period, the appropriate use of bupivacaine
      increased from 14.3% to 49.4% (difference 35.2%, 95% CI 20.9 to 49.4, p<0.001);
      the appropriate use of lignocaine and bupivacaine increased from 38.3% to 59.5%
      (difference 21.1%, 95% CI 7.3 to 35.0, p = 0.003); the total number of
      bupivacaine ampoules issued rose by 308% (from 60 to 245); the total number of
      lignocaine ampoules issued decreased by 6.7% (from 2008 to 1873); and the number
      of files with adequate documentation increased from 56.3% to 63.4% (difference
      7.1%, 95% CI -3.5 to 17.7, p = 0.20). CONCLUSION: The education initiative
      resulted in significant improvements in the evidence-based use of bupivacaine,
      and its adoption by others is recommended.

PMID- 20029000
TI  - Emergency Medicine Questions (EMQs): theme: vascular access.

PMID- 20029001
TI  - How have changes to out-of-hours primary care services since 2004 affected
      emergency department attendances at a UK District General Hospital? A
      longitudinal study.
AB  - BACKGROUND: The delivery of out-of-hours primary medical care in the United
      Kingdom has changed substantially since 2004, and there has been little
      examination of the effect that this has on secondary care. AIM: The authors aimed
      to quantify the change in patient type presenting to our emergency department.
      METHODS: In this study, routinely collected coding data before, during and after
      the changes were analysed. Each September and October between 1999 and 2006 were
      included. RESULTS: There was a steady increase in all attendances at our
      emergency department. The number and proportions of patients with non-traumatic
      conditions rose steadily throughout the study period. The number of patients
      presenting with traumatic conditions stayed the same. The number of patients
      presenting with non-traumatic conditions out-of-hours rose after the changes were
      implemented. INTERPRETATION: The changes to the provision of out-of-hours primary
      care have been associated with an increase in patients with non-traumatic
      attendances presenting to our emergency department. This effect is most marked
      outside of office hours.

PMID- 20029002
TI  - Emergency department attendance by children at risk of abuse.
AB  - BACKGROUND: Frequency of emergency department (ED) attendance has long been
      thought to be a risk factor for child abuse. The aim of this study was to test
      this assumption by comparing the ED attendances of at-risk children (before being
      placed on a child protection register) with the attendances of an age-matched
      control group (before an index attendance) Method: A group of 220 children (aged
      0-12 years inclusive) were identified from the two child protection registers in
      the Shropshire area in 2006. The ED attendances of these children in the 2 years
      before registration were identified using the computer records of the two local
      EDs. A control group of 150 children for each year of age (0-12 years inclusive)
      was then identified from ED attendances between October and December 2006. The
      attendances of these children in the 2 years before this index attendance were
      obtained. The data for these two groups of children were then compared. RESULTS:
      The at-risk children did not attend the EDs more frequently than did the children
      in the control group. CONCLUSION: The identification of children who attend EDs
      frequently may be useful for other reasons but is unlikely to be an effective way
      to detect child abuse.

PMID- 20029003
TI  - Oesophagography and oesophagoscopy are not necessary in patients with spontaneous
      pneumomediastinum.
AB  - BACKGROUND: Because the condition is rare, the proper assessment of spontaneous
      pneumomediastinum (SPM) remains controversial. The purpose of this study was to
      determine whether additional oesophageal investigations beyond chest x ray and
      chest computed tomography (CT) scan are necessary for the diagnosis of SPM.
      METHODS: The medical records of 25 patients diagnosed and treated for SPM from
      March 1986 to December 2007 were retrospectively reviewed. RESULTS: There were 22
      men and 3 women, with a median age of 19 years (range 15-57 years). All patients
      received chest x rays, which revealed air shadows within the mediastinum or
      subcutaneous emphysema in 24 patients. Twenty-two patients underwent chest CT
      scans, which showed pneumomediastinum in all cases. Oesophagography was performed
      in 14 patients and oesophagoscopy in three. All oesophagographies and
      oesophagoscopies were clear. Despite conservative treatment, no patients
      developed mediastinitis or complications associated with oesophageal injury.
      CONCLUSIONS: Chest x ray and CT scan are sufficient to diagnose SPM. Additional
      diagnostic assessments such as oesophagography and oesophagoscopy are not
      necessary in patients without evidence of mediastinitis or a history of
      oesophageal injury.

PMID- 20029004
TI  - Evaluation of morning report in an emergency medicine department.
AB  - BACKGROUND: Morning report is considered as an important educational tool in
      different branches of medicine. The purpose of the present study was to examine
      the method of case selection, the leadership, the participant's satisfaction and
      the educational value of morning report held in our centre. METHOD: In September
      2007, a formal feedback about the morning report was provided by questionnaire
      surveys. The data on the method of case selection, the leadership, the
      participant's satisfaction and the educational value of the sessions were
      collected from the residents, medical students and the academic staff in
      emergency medicine department. Each questionnaire also contained an open-ended
      question, asking for the responders' suggestions for improving these sessions.
      RESULTS: 73.2% of the responders were satisfied with the current model of the
      conference hall. The data showed that 46.3% of the participants believed these
      sessions are held for giving the medical team the required information and 65.9%
      for solving the patient's problems. The data showed that the participants had
      evaluated the presentation strategy to be good; however, the presentation pattern
      was reported to be traditional and based on differential diagnosis in 53.7% of
      the cases and modern problem oriented in only 39%. CONCLUSION: Most participants
      considered morning report sessions held in our hospital to be effective in the
      way it is; however, issues such as communication skill, emergency department
      management, critical thinking, ethics, professionalism and evidence-based
      medicine should also be added to the sessions.

PMID- 20029005
TI  - Evaluation of a bedside immunotest to predict individual anti-tetanus
      seroprotection: a prospective concordance study of 1018 adults in an emergency
      department.
AB  - BACKGROUND: Unscheduled tetanus prophylaxis (UTP) used in the emergency room (ER)
      in patients with wounds who are unaware of their vaccination history is erroneous
      in 40% of cases. Evaluation of bedside tetanus immunity with the Tetanos Quick
      Stick (TQS) test may improve UTP. OBJECTIVES: To show that (1) a positive TQS
      result reflects immunity to tetanus; and (2) TQS is reproducible by ER workers.
      METHODS: In a prospective concordance study, immunity to tetanus of patients with
      wounds was assessed by two techniques: (1) TQS at the bedside, which detects
      specific tetanus antitoxins at concentrations > or =0.2 IU/ml in whole blood or >
      or =0.1 IU/ml in serum; (2) ELISA in the laboratory (threshold >0.1 IU/ml). The
      study comprised three groups: (A) healthcare personnel self-tested with the two
      techniques to determine the effect of training; (B) selected patients with wounds
      were double-tested with TQS by two healthcare providers whose readings were
      compared to test reproducibility; and (C) all patients with wounds aged > or =15
      years were consecutively included. RESULTS: Of 1018 individuals included, 60 were
      in group A, 50 were in group B and 908 were in group C. 403 patients who were not
      included were similar to those included for age, vaccination history and types of
      wounds. The reproducibility of the test was 98%. TQS sensitivity was 83.0%,
      specificity 97.5%, positive predictive value 99.6% and negative predictive value
      42.9%. CONCLUSIONS: TQS reliably predicts tetanus immunity and is reproducible by
      healthcare providers. Although it may not accurately discriminate between
      patients with ongoing and declining immunity, it is currently the most sensitive
      and specific tool for guiding tetanus prophylaxis and should be included in
      current guidelines on UTP.

PMID- 20029006
TI  - Inappropriate use and interpretation of D-dimer testing in the emergency
      department: an unexpected adverse effect of meeting the "4-h target".
AB  - INTRODUCTION: D-dimer tests were inappropriately overused in our emergency
      department as a result of bloods being taken before clinical assessment to help
      meet the "4-hour target". We introduced a multifaceted intervention to reduce the
      number of inappropriate D-dimer tests. The secondary aim was to improve the
      diagnostic workup of suspected pulmonary embolism (PE). METHOD: Rate of D-dimer
      test and ventilation/perfusion scan requests were compared before, during and
      after a staggered intervention at two hospitals in one National Health Service
      Trust. Audits before and after the intervention were done to determine whether
      test use was appropriate and whether the diagnostic workup was complete. RESULTS:
      At hospital 1, D-dimer testing after the intervention was almost halved: ratio
      0.59 (95% CI 0.55 to 0.63) (p<0.0001). There was also a small reduction at
      hospital 2 (control): rate 0.88 (95% CI 0.78 to 0.99) (p = 0.03). After the
      formal introduction of change at hospital 2, there was a further reduction in
      tests: ratio 0.67 (95% CI 0.58 to 0.76) (p<0.0001). In hospital 1, pretest
      probability assessment improved by 42% (p = 0.0004) and D-dimer test use was
      reduced by 12.5% (p = 0.04) between audits. Improvement in the use of D-dimer
      test according to the pathway was not significant (32.5%, p = 0.11), and there
      was no change in the proportion of patients with completion of their diagnostic
      workup for PE: 47.6% (95% CI 38.3% to 56%) before and 45.6% (95% CI 38.3% to
      53.1%) after the intervention. CONCLUSION: Implementation of a multifaceted
      change program reduced the number of D-dimer test requests in both hospitals and
      may have improved the diagnostic workup for PE at hospital 1. Processes that
      speed patient transit through the emergency department may impact negatively on
      other aspects of patient care. This should be the subject of further studies.

PMID- 20029007
TI  - The impact of a temporary ice rink on a local emergency department service.
AB  - Ice skating is becoming more popular throughout the UK, with temporary ice rinks
      opening in many city centres during holiday periods, especially during Christmas.
      Data were collected from patients who presented to the local emergency department
      with injuries sustained on a nearby city-centre temporary ice rink. Injuries
      related to ice rinks accounted for 0.76% of all emergency department attendances
      and represented 0.29% of ice rink participants (2.9 per 1000). Women in the older
      age range sustained the most significant injuries. Our study has shown that the
      rate of injuries per 1000 ice rink participants is comparable with data recorded
      when a new ice rink is opened.

PMID- 20029009
TI  - Frenal injury in children is not pathognomic of non-accidental injury.
AB  - Upper labial frenal tear in infants is classically taught as having associations
      with non-accidental injury. Collection of data for a 12-month period in our
      paediatric facial injury study revealed that this injury pattern is common in
      ambulant children and was associated with other facial trauma. In assessing the
      possibility of this injury being due to abuse, the importance of the mobility of
      the child and the mechanism of the injury are paramount.

PMID- 20029008
TI  - Google governance: increasing the effectiveness of critical care physicians
      through the use of an online usergroup.
AB  - AIMS: The aim of this study was to describe the use of an online user group to
      enhance communication and productivity by critical care specialists. METHODS: In
      this article, we provide a description of the first 6 months of use of an online
      user group by senior retrieval physicians. RESULTS: Initially developed as a
      communication and online discussion tool, our online user group evolved to
      include a number of other utilities that support clinical governance. These
      included a repository for useful files, educational presentations, online
      rostering and "portfolio pages", updating aspects of an individual specialist's
      non-clinical activity. Its applications continue to evolve in number and utility.
      Participating physicians perceive an increase in organisational efficiency.
      CONCLUSIONS: An online user group such as Google Groups may provide powerful
      support to an organisation's clinical governance. We recommend this tool to other
      services with limited administrative personnel.

PMID- 20029010
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: blood component therapy in trauma patients requiring massive
      transfusion.

PMID- 20029012
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: potato peel dressings for burn wounds.

PMID- 20029013
TI  - Towards evidence based emergency medicine: best BETs from theManchester Royal
      Infirmary. BET 3: chlordiazepoxide, the management of alcohol withdrawal and the
      kindling effect.

PMID- 20029014
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 4: ACE inhibitors in addition to standard treatments in acute
      heart failure.

PMID- 20029015
TI  - Chest compression first aid for respiratory arrest due to acute asphyxic asthma.
AB  - This report demonstrates the importance of including external chest compression
      as a method of resuscitation in first aid for cases of life-threatening asphyxic
      asthma. Chest compression may be the only way that death of such patients may be
      avoided. Three such patients, two with respiratory arrest, were successfully
      treated by external chest compression. During the 1960s, there was an increase in
      asthma deaths, 81% of which occurred unexpectedly, outside the hospital. This
      coincided with the abandonment of the trusted methods of chest compression and
      the introduction of mouth-to-mouth resuscitation. Acute asphyxic asthma was the
      most common cause of death. In acute asphyxic asthma, the chest wall does not
      deflate spontaneously. The trapped air must be expelled by external compression.
      Mouth-to-mouth resuscitation may not work because air is being blown in while
      none escapes.

PMID- 20029016
TI  - Back pain after wild mushroom consumption.

PMID- 20029017
TI  - Defining a standard medication kit for prehospital and retrieval physicians: a
      comprehensive review.
AB  - BACKGROUND: There is little consolidated evidence for which prehospital and
      retrieval drugs a given service should carry. OBJECTIVES: To suggest a core group
      of drugs based on the best evidence currently available. METHODS: This paper has
      reviewed documents from recognised evidence-based sources and put together an
      initial skeleton for an evidence-based drug pack. RESULTS: The resultant list of
      drugs is divided up into core agents with suggestions for regional variations.
      This may be of particular interest to de novo services. CONCLUSIONS: This review
      offers a starting point for services based on the evidence currently available.
      It is hoped that prehospital and retrieval clinicians will start to look
      analytically at what they carry and, through a process of audit, aim to improve
      the evidence in this area. Future reviews and comparisons of worldwide
      prehospital and retrieval databases are suggested.

PMID- 20029018
TI  - Delayed presentation following accidental inhalation of a pushpin.
AB  - A previously fit and well 18-year-old woman presented to the accident and
      emergency department following referral by her general practitioner with a
      provisional diagnosis of appendicitis. The history obtained from the patient
      revealed the presence of a bitemporal headache with associated neck stiffness,
      photophobia and vomiting for approximately 1.5 weeks. The patient complained of
      abdominal pain localised to her right iliac fossa and anorexia for approximately
      1 week. She also noted the presence of a cough productive of green sputum for 3
      weeks. A chest radiograph was obtained which showed a large area of consolidation
      in the right lower lobe consistent with infection and a linear density in keeping
      with a metallic foreign body. Following review of the chest radiograph, the
      patient was interviewed further and recalled having inhaled a pushpin
      approximately 1 year before her presentation. Aspiration of foreign bodies is
      relatively common in children and is often associated with delayed diagnosis and
      high morbidity. To prevent delayed diagnosis, characteristic symptoms and
      clinical and radiological signs of foreign body aspiration should be checked in
      all suspected cases and a low index of suspicion for ordering additional imaging
      or using bronchoscopy for diagnostic purposes should be employed.

PMID- 20029019
TI  - Possible interaction between pomegranate juice and warfarin.
AB  - Pomegranate juice is growing in popularity in the UK. We report a potential
      interaction between pomegranate juice and warfarin. Laboratory studies have shown
      that pomegranate juice inhibits cytochrome P450 enzymes involved in warfarin
      metabolism. As with previous reports of interactions between food and warfarin,
      this case does not definitively prove the association between pomegranate juice
      consumption and increased warfarin bioactivity but highlights the importance of
      taking a complete drug, food and juice history when assessing patients with
      unstable anticoagulation.

PMID- 20029020
TI  - An adolescent athlete with groin and hip pain.
AB  - The case report is presented of a 14-year-old boy with persistent right hip and
      groin pain. After failing to respond to conventional management, the patient was
      admitted and investigated. He had a fever and raised inflammatory markers. MRI of
      the pelvis revealed pyomyositis of the right adductor compartment extending into
      the pelvis. Pyomyositis should be considered in a patient with pain
      disproportionate to the physical examination findings.

PMID- 20029021
TI  - The radiology investigation of renal colic in the emergency department.

PMID- 20029022
TI  - Inadvertent prostatic stimulation causing cardioversion of unstable
      superventricular tachycardia.

PMID- 20029024
TI  - Reporting positive results in OEM.

PMID- 20029025
TI  - Maternal occupation and the risk of birth defects: an overview from the National
      Birth Defects Prevention Study.
AB  - OBJECTIVES: To examine the association between a spectrum of 24 maternal
      occupations and 45 birth defects for hypothesis generating purposes. METHODS:
      Cases of isolated and multiple birth defects (n = 8977) and all non-malformed
      live-born control births (n = 3833) included in the National Birth Defects
      Prevention Study (NBDPS) with estimated dates of delivery from 1 October 1997
      through 31 December 2003 were included. A computer-assisted telephone interview
      with mothers was conducted. Occupational coding using the 2000 Standard
      Occupational Classification System and the 1997 North American Industry
      Classification System was completed for all jobs held by mothers. Jobs held from
      1 month before pregnancy to the end of the third pregnancy month were considered
      exposures. Logistic regression models were run, adjusted for potential
      confounders. We also used a Bayesian approach to logistic regression. RESULTS:
      Approximately 72% of case mothers and 72% of control mothers in the NBDPS were
      employed. Several occupational groups were positively associated with one or more
      birth defects, including janitors/cleaners, scientists and electronic equipment
      operators. Using standard logistic regression, we found 42 (26 for Bayesian)
      significantly elevated risks of birth defects in offspring of working mothers. In
      addition, several other occupational groups were found to be negatively
      associated with one or more birth defects, including teachers and healthcare
      workers. Using standard logistic regression, we found 12 (11 for Bayesian)
      significantly reduced risks of birth defects among offspring of working women.
      CONCLUSIONS: Results from these analyses can be used for hypothesis generating
      purposes and guiding future investigations of occupational exposures and birth
      defects.

PMID- 20029026
TI  - Discrete time hazards models for occupational and environmental cohort analyses.
AB  - OBJECTIVE: To discuss the use of discrete time hazards models for the analysis of
      occupational and environmental cohort data. METHODS: Analytical data structures
      and regression methods for discrete time hazards models are described. This
      approach is illustrated via analyses of data from a study of mortality in a
      cohort of chemical workers exposed to dioxin. RESULTS AND CONCLUSIONS: Analyses
      employing a discrete time hazards model facilitate examination of observed and
      expected counts, the calculation of attributable fractions, and empirical
      description of the estimated hazard rates. In addition, this approach can be used
      to fit non-multiplicative models, such as the linear hazards ratio model (which
      has been employed in epidemiological analyses of a variety of environmental and
      occupational exposures).

PMID- 20029028
TI  - Channeling calcium: a shared mechanism for exocytosis-endocytosis coupling.
AB  - Cell surface area is maintained in most cells by coupling exocytotic activity to
      compensatory endocytosis, a process that specifically retrieves membrane inserted
      by exocytosis. Although such coupling mechanisms seem to be ubiquitous, the
      mechanisms through which these membrane trafficking events are linked have
      remained elusive. A mechanism for coupling exocytosis to endocytosis in fruit fly
      nerve terminals that depends on the exocytotic insertion of vesicular calcium
      channels into the plasma membrane has recently been identified. This coupling
      mechanism resembles one previously described in sea urchin eggs. Here, I compare
      the similarities and differences of the processes involved in linking exocytosis
      to endocytosis in these two invertebrate systems and speculate on whether the
      vertebrate coupling mechanism might also depend on vesicular channels.

PMID- 20029029
TI  - Regulation of epidermal growth factor receptor trafficking by lysine deacetylase
      HDAC6.
AB  - Binding of epidermal growth factor (EGF) to its receptor leads to receptor
      dimerization, assembly of protein complexes, and activation of signaling networks
      that control key cellular responses. Despite their fundamental role in cell
      biology, little is known about protein complexes associated with the EGF receptor
      (EGFR) before growth factor stimulation. We used a modified membrane yeast two
      hybrid system together with bioinformatics to identify 87 candidate proteins
      interacting with the ligand-unoccupied EGFR. Among them was histone deacetylase 6
      (HDAC6), a cytoplasmic lysine deacetylase, which we found negatively regulated
      EGFR endocytosis and degradation by controlling the acetylation status of alpha
      tubulin and, subsequently, receptor trafficking along microtubules. A negative
      feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr(570)
      resulted in reduced deacetylase activity and increased acetylation of alpha
      tubulin. This study illustrates the complexity of the EGFR-associated interactome
      and identifies protein acetylation as a previously unknown regulator of receptor
      endocytosis and degradation.

PMID- 20029030
TI  - Tumor suppression by PTEN requires the activation of the PKR-eIF2alpha
      phosphorylation pathway.
AB  - Inhibition of protein synthesis by phosphorylation of the alpha subunit of
      eukaryotic translation initiation factor 2 (eIF2) at Ser(51) occurs as a result
      of the activation of a family of kinases in response to various forms of stress.
      Although some consequences of eIF2alpha phosphorylation are cytoprotective,
      phosphorylation of eIF2alpha by RNA-dependent protein kinase (PKR) is largely
      proapoptotic and tumor suppressing. Phosphatase and tensin homolog deleted from
      chromosome 10 (PTEN) is a tumor suppressor protein that is mutated or deleted in
      various human cancers, with functions that are mediated through phosphatase
      dependent and -independent pathways. Here, we demonstrate that the eIF2alpha
      phosphorylation pathway is downstream of PTEN. Inactivation of PTEN in human
      melanoma cells reduced eIF2alpha phosphorylation, whereas reconstitution of PTEN
      null human glioblastoma or prostate cancer cells with either wild-type PTEN or
      phosphatase-defective mutants of PTEN induced PKR activity and eIF2alpha
      phosphorylation. The antiproliferative and proapoptotic effects of PTEN were
      compromised in mouse embryonic fibroblasts that lacked PKR or contained a
      phosphorylation-defective variant of eIF2alpha. Induction of the pathway leading
      to phosphorylation of eIF2alpha required an intact PDZ-binding motif in PTEN.
      These findings establish a link between tumor suppression by PTEN and inhibition
      of protein synthesis that is independent of PTEN's effects on phosphoinositide 3'
      kinase signaling.

PMID- 20029031
TI  - Cbl controls EGFR fate by regulating early endosome fusion.
AB  - Amino acid residues 1 to 434 of the E3 ubiquitin ligase Cbl control signaling of
      the epidermal growth factor receptor (EGFR) by enhancing its ubiquitination, down
      regulation, and lysosomal degradation. This region of Cbl comprises a tyrosine
      kinase-binding domain, a linker region, a really interesting new gene finger
      (RF), and a subset of the residues of the RF tail. In experiments with full
      length alanine substitution mutants, we demonstrated that the RF tail of Cbl
      regulated biochemically distinct checkpoints in the endocytosis of EGFR. The Cbl-
      and ubiquitin-dependent degradation of the regulator of internalization hSprouty2
      was compromised by the Val(431)--> Ala mutation, whereas the Cbl- and EGFR
      dependent dephosphorylation or degradation of the endosomal trafficking regulator
      Hrs was compromised by the Phe(434)--> Ala mutation. Deregulated phosphorylation
      of Hrs correlated with inhibition of the fusion of early endosomes and of the
      degradation of EGFR. This study provides the first evidence that Cbl regulates
      receptor fate by controlling the fusion of sorting endosomes. We postulate that
      it does so by modulating the abundance of tyrosine-phosphorylated Hrs.

PMID- 20029032
TI  - COPD as a disease of children: hype or hope for better understanding?

PMID- 20029033
TI  - A Bill of "Rights" for patients with COPD: the "right" therapy for the "right"
      patient at the "right" time.

PMID- 20029034
TI  - Childhood obstructive sleep apnoea: to treat or not to treat, that is the
      question.

PMID- 20029035
TI  - Seldinger chest drain insertion: simpler but not necessarily safer.

PMID- 20029037
TI  - Meta-analysis of the risk of mortality with salmeterol and the effect of
      concomitant inhaled corticosteroid therapy.
AB  - BACKGROUND: There is concern that long-acting beta agonist (LABA) drugs may
      increase the risk of asthma mortality. METHODS: A meta-analysis was conducted of
      asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline
      database that compared salmeterol with a non-LABA comparator treatment in asthma.
      The Peto one-step method was used to determine the risk overall (all studies) and
      in derived datasets based on inhaled corticosteroid (ICS) use. RESULTS: There
      were 35 asthma deaths in 215 studies with 106,575 subjects. Two studies (SMART
      and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely
      reflecting the characteristics of these studies. The odds ratio for risk of
      asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo
      controlled studies the risk of death from asthma in patients not prescribed ICS
      was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed
      ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which
      patients were randomised to receive the combination salmeterol/fluticasone
      propionate inhaler or ICS, there were no asthma deaths among 22,600 patients.
      CONCLUSIONS: Salmeterol monotherapy in asthma increases the risk of asthma
      mortality and this risk is reduced with concomitant ICS therapy. There is no
      evidence that combination salmeterol/fluticasone propionate therapy is associated
      with an increased risk of asthma mortality, although this interpretation is
      limited by the low statistical power of available studies.

PMID- 20029038
TI  - Once bitten, twice shy.

PMID- 20029040
TI  - Diffuse interlobular septal thickening in a coal miner.
AB  - Diffuse interlobular septal thickening (DIST) is an abnormality seen on high
      resolution CT (HRCT) scanning of the thorax. While DIST may be present to
      variable extents in a number of lung conditions, it is uncommon as a predominant
      finding except in a few entities. This report features an ex-coal miner, thought
      to have coal workers' pneumoconiosis (CWP), in whom the HRCT scan showed no
      evidence of CWP and instead showed DIST. The patient's condition progressed
      incessantly towards death from severe secondary pulmonary hypertension. The case
      links fatal pulmonary hypertension to DIST, a pattern not previously described in
      coal workers.

PMID- 20029042
TI  - Upper airway. 3: Sinonasal involvement in chronic obstructive pulmonary disease.
AB  - This review presents the evidence that chronic obstructive pulmonary disease
      (COPD) is associated with significant sinonasal symptoms, inflammation and airway
      obstruction. Upper airway symptoms in COPD cause impairment to quality of life.
      The severity of upper airway involvement relates to that present in the lower
      airway, suggesting that the nose may be used to model the lung in COPD. More
      importantly, relationships between upper and lower airway bacteria and
      inflammation, and the association between sinusitis and treatment failure at
      exacerbation raise the possibility that nasal intervention in COPD may not only
      improve health status but may also affect important clinical outcomes such as
      exacerbation frequency.

PMID- 20029043
TI  - What size parapneumonic effusions should be sampled?

PMID- 20029044
TI  - Endobronchial metastasis of osteosarcoma presenting as position-dependent and
      variable airway obstruction of the trachea.

PMID- 20029045
TI  - Mislocalization of SLP-76 leads to aberrant inflammatory cytokine and
      autoantibody production.
AB  - Central and peripheral tolerance is required to prevent immune responses to self
      antigens. We now present a mouse model in which wild-type (WT) SH2 domain
      containing leukocyte phosphoprotein of 76 kDa (SLP-76) has been constitutively
      targeted to the membrane, where CD4+ T cells become spontaneously dysregulated
      and develop an inflammatory phenotype. Mice bearing membrane-targeted SLP-76
      (MTS) have a partial T-cell lymphopenia and impaired signaling though the mature
      T-cell receptor. The CD4+ T cells that develop in these mice possess an activated
      like phenotype and are skewed toward the inflammatory T(H)1 and T(H)17 lineages.
      MTS mice also spontaneously develop autoantibodies at an early age. To rule out
      abnormal thymic selection as the sole cause of the MTS phenotype, we expressed WT
      SLP-76 along with the MTS followed by deletion of the WT allele in peripheral T
      cells. The peripheral MTS-expressing T cells demonstrate skewed cytokine
      responses when transferred into lymphopenic hosts. Thus, the abnormal effector T
      cell phenotype still occurs in the presence of preserved central and peripheral
      tolerance, suggesting that diminished T-cell receptor signaling can promote
      skewed T-cell responses.

PMID- 20029046
TI  - Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative
      feedback loop in acute myeloid leukemia.
AB  - Transcription factor CCAAT enhancer binding protein alpha (C/EBPalpha) is
      essential for granulopoiesis and its function is deregulated in leukemia.
      Inhibition of E2F1, the master regulator of cell-cycle progression, by C/EBPalpha
      is pivotal for granulopoiesis. Recent studies show microRNA-223 (miR-223), a
      transcriptional target of C/EBPalpha, as a critical player during granulopoiesis.
      In this report, we demonstrate that during granulopoiesis microRNA-223 targets
      E2F1. E2F1 protein was up-regulated in miR-223 null mice. We show that miR-223
      blocks cell-cycle progression in myeloid cells. miR-223 is down-regulated in
      different subtypes of acute myeloid leukemia (AML). We further show that E2F1
      binds to the miR-223 promoter in AML blast cells and inhibits miR-223
      transcription, suggesting that E2F1 is a transcriptional repressor of the miR-223
      gene in AML. Our study supports a molecular network involving miR-223,
      C/EBPalpha, and E2F1 as major components of the granulocyte differentiation
      program, which is deregulated in AML.

PMID- 20029047
TI  - Single-agent arsenic trioxide in the treatment of children with newly diagnosed
      acute promyelocytic leukemia.
AB  - The aim of this study was to determine the efficacy and safety of treatment of
      pediatric acute promyelocytic leukemia (APL) with single-agent arsenic trioxide
      (ATO). A total of 19 children (< or = 15 years of age) with newly diagnosed APL
      were treated with single-agent ATO for remission induction and postremission
      therapy. Seventeen of the children (89.5%) achieved complete hematologic
      remission, and 2 early deaths occurred from intracranial hemorrhage. ATO-induced
      leukocytosis was observed in 13 (68.4%) patients. Other ATO-related toxicities
      were minimal and transient. Postremission ATO therapy continued for 3 years; the
      most common side effect was ATO-induced neutropenia. With a median follow-up of
      53 months (range, 23-76 months), the calculated 5-year overall survival and event
      free survival were 83.9% and 72.7%, respectively, which are comparable with
      results achieved by the use of ATRA plus chemotherapy, which is the standard
      therapy for APL. No chronic arsenic toxicity or second malignancies were found
      during the follow-up period, and arsenic retention was not significant in
      patients off treatment more than 24 months. ATO resistance was observed in only 1
      patient with a complex karyotype. The results indicate the high efficacy and
      safety of single-agent ATO regimens in the treatment of children with de novo
      APL.

PMID- 20029048
TI  - Combined effect of total nucleated cell dose and HLA match on transplantation
      outcome in 1061 cord blood recipients with hematologic malignancies.
AB  - Both total nucleated cell (TNC) dose and human leukocyte antigen (HLA)-match
      affect the outcome of cord blood (CB) transplantation. However, how to prioritize
      these characteristics in unit selection is not established. Therefore, we
      analyzed the outcomes of 1061 patients who received single-unit myeloablative CB
      transplantation for leukemia or myelodysplasia. TNC dose and HLA-match each
      affected survival via their effect on transplant-related mortality (TRM); neither
      was associated with relapse. Therefore, TRM was the focus of multivariate
      analyses combining dose and HLA-match. Compared with our 1 HLA-mismatch (MM)
      reference group with TNC 2.5 to 4.9 x 10(7)/kg, recipients of 0 MM units had the
      lowest TRM regardless of dose (relative risk [RR] = 0.4, P = .019). TRM for
      recipients of 1- or 2-MM units with TNC 5.0 x 10(7)/kg or greater was similar to
      the reference group (RR = 0.8, P = .391 and RR = 1.0, P = .847) despite their
      greater dose. Recipients of 2 MM units with TNC 2.5 to 4.9 x 10(7)/kg had a
      greater TRM (RR = 1.5, P = .014), and those with 1 or 2 MM and TNC less than 2.5
      x 10(7)/kg or 3 MM did substantially worse. These findings support new unit
      selection criteria that take into account both TNC dose and HLA-match and have
      important implications for the size of the global CB inventory needed to find an
      optimum CB graft.

PMID- 20029049
TI  - Bivariate genetic analyses of stuttering and nonfluency in a large sample of 5
      year-old twins.
AB  - PURPOSE: Behavioral genetic studies of speech fluency have focused on
      participants who present with clinical stuttering. Knowledge about genetic
      influences on the development and regulation of normal speech fluency is limited.
      The primary aims of this study were to identify the heritability of stuttering
      and high nonfluency and to assess the relative contribution of genetic and
      environmental factors to the correlation between these 2 fluency phenotypes.
      METHOD: Information on 6 specific speech fluency behaviors was obtained by
      maternal report for over 10,500 5-year-old Dutch twin pairs. RESULTS: Genetic
      analyses revealed that both fluency phenotypes were moderately heritable, with
      heritability estimates of 42% and 45% for probable stuttering and high
      nonfluency, respectively. Shared environmental factors were also significant,
      explaining 44% of the individual differences in probable stuttering and 32% in
      nonfluency. For both phenotypes, the magnitude of the genetic and environmental
      influences did not differ between boys and girls. The overlap between the 2
      traits was substantial (tetrachoric correlation was .72). A bivariate genetic
      analysis showed that this overlap was due to both overlapping genetic and
      environmental influences. CONCLUSIONS: These findings provide a foundation to
      justify further studies in normal fluency control, a scientific area that has
      received little cross-disciplinary attention.

PMID- 20029050
TI  - Intonation contrast in Cantonese speakers with hypokinetic dysarthria associated
      with Parkinson's disease.
AB  - PURPOSE: Speech produced by individuals with hypokinetic dysarthria associated
      with Parkinson's disease (PD) is characterized by a number of features including
      impaired speech prosody. The purpose of this study was to investigate intonation
      contrasts produced by this group of speakers. METHOD: Speech materials with a
      question-statement contrast were collected from 14 Cantonese speakers with PD.
      Twenty listeners then classified the productions as either questions or
      statements. Acoustic analyses of F0, duration, and intensity were conducted to
      determine which acoustic cues distinguished the production of questions from
      statements, and which cues appeared to be exploited by listeners in identifying
      intonational contrasts. RESULTS: The results show that listeners identified
      statements with a high degree of accuracy, but the accuracy of question
      identification ranged from 0.56% to 96% across the 14 speakers. The speakers with
      PD used similar acoustic cues as nondysarthric Cantonese speakers to mark the
      question-statement contrast, although the contrasts were not observed in all
      speakers. Listeners mainly used F0 cues at the final syllable for intonation
      identification. CONCLUSION: These data contribute to the researchers'
      understanding of intonation marking in speakers with PD, with specific
      application to the production and perception of intonation in a lexical tone
      language.

PMID- 20029051
TI  - Perception of wet vocal quality in identifying penetration/aspiration during
      swallowing.
AB  - PURPOSE: In the present study, the authors investigated the association between
      wet vocal quality (WVQ) and prandial material in the larynx during phonation. The
      presence of such material is indicative of oropharyngeal dysphagia and results
      from entry of material into the laryngeal vestibule during swallowing. The
      primary aim of the study was to determine whether clinicians reliably perceive
      WVQ during phonation when prandial material is in the larynx. METHOD: Seventy
      eight subjects underwent videofluoroscopic swallow study, and simultaneous
      recording of time-linked videofluoroscopic and acoustic data was conducted during
      postswallow phonation. Experienced dysphagia clinicians then rated randomized
      audio samples for presence or absence of WVQ. RESULTS: WVQ is not reliably
      perceived by clinicians when material is present in the larynx in the region of
      the glottis during phonation, and there is a high degree of interrater
      variability for perceptual judgments of wetness. CONCLUSIONS: Material in the
      larynx during phonation may result in multiple voice quality percepts, and even
      experienced clinicians may not be adept at identifying the perceptual
      consequences of this. Observation of laryngeal physiology during voicing when
      material is in the larynx using vocal tract imaging can improve reliability in
      the identification of wet vocal quality.

PMID- 20029052
TI  - Effects of masking noise on laryngeal resistance for breathy, normal, and pressed
      voice.
AB  - PURPOSE: The purpose of the present study was to explore the effects of masking
      noise on laryngeal resistance for breathy, normal, and pressed voice in vocally
      trained women. METHOD: Eighteen vocally trained women produced breathy, normal,
      and pressed voice across 7 fundamental frequencies during a repeated CV utterance
      of /pi/ under normal and masked auditory feedback. Dependent variables were mean
      and standard deviation of laryngeal resistance (LR; cmH2O/l/s). RESULTS: LR
      values for breathy and normal voice remained constant across normal and masked
      auditory feedback, whereas LR values for pressed voice increased significantly
      from normal to masked auditory feedback. CONCLUSIONS: The results suggest that
      both voice pattern and feedback condition influenced the stability of the LR
      data. Specifically, the pressed voice pattern may be more susceptible to auditory
      feedback influence because it was less stable than the breathy and the normal
      voice patterns. Future investigation should continue to explore the relevance of
      auditory feedback for theoretical and clinical issues surrounding voice.

PMID- 20029053
TI  - Randomized controlled trial of video self-modeling following speech restructuring
      treatment for stuttering.
AB  - PURPOSE: In this study, the authors investigated the efficacy of video self
      modeling (VSM) following speech restructuring treatment to improve the
      maintenance of treatment effects. METHOD: The design was an open-plan, parallel
      group, randomized controlled trial. Participants were 89 adults and adolescents
      who undertook intensive speech restructuring treatment. Post treatment,
      participants were randomly assigned to 2 trial arms: standard maintenance and
      standard maintenance plus VSM. Participants in the latter arm viewed stutter-free
      videos of themselves each day for 1 month. RESULTS: The addition of VSM did not
      improve speech outcomes, as measured by percent syllables stuttered, at either 1
      or 6 months postrandomization. However, at the latter assessment, self-rating of
      worst stuttering severity by the VSM group was 10% better than that of the
      control group, and satisfaction with speech fluency was 20% better. Quality of
      life was also better for the VSM group, which was mildly to moderately impaired
      compared with moderate impairment in the control group. CONCLUSIONS: VSM
      intervention after treatment was associated with improvements in self-reported
      outcomes. The clinical implications of this finding are discussed.

PMID- 20029054
TI  - Chronic subjective dizziness versus conversion disorder: discussion of clinical
      findings and rehabilitation.
AB  - PURPOSE: Audiologists frequently encounter patients who complain of chronic
      dizziness or imbalance, in the absence of active vestibular or neurological
      deficits. Knowledge about conditions that cause this clinical presentation will
      allow audiologists to make important contributions to accurate diagnosis and
      effective management of these patients. This article reviews 2 such conditions,
      chronic subjective dizziness (CSD) and conversion disorder. METHOD: A case of CSD
      and another of conversion disorder are presented, with a literature review of
      their clinical presentations, key diagnostic features, and treatment strategies.
      The role of the audiologist in assessing patients with these conditions and
      facilitating appropriate treatment referrals is discussed. CONCLUSIONS: The
      audiologist is in a key position to identify individuals with CSD and conversion
      disorder, 2 conditions that can be effectively managed if properly recognized.
      The authors demonstrate an effective team approach program that includes the
      audiologist's contribution to differential diagnosis, education of patients and
      other clinicians about these conditions, and development of recommendations for
      neurological, psychiatric, otologic, and physical therapy referrals.

PMID- 20029055
TI  - Covariance 99mTc-exametazime SPECT patterns in Alzheimer's disease and dementia
      with Lewy bodies: utility in differential diagnosis.
AB  - (99m)Tc-exametazime single photon emission computed tomography (SPECT) scans of
      36 patients with Alzheimer's disease (AD) and 30 with dementia with Lewy bodies
      (DLB) underwent region of interest (ROI) and principal component analysis (PCA).
      Principal component analysis was performed on the entire ROI data set. Principal
      components (PCs) were obtained, representing common intercorrelated regions in AD
      and DLB. Topographic expression that signified the extent to which a participant
      expressed the topographic covariance pattern was derived and used as a
      discriminatory variable. Principal components were identified, accounting for 77%
      of total data variance. Significant (PC x group) interaction was observed (P <
      .001). Topographic expression was significantly higher in DLB than AD (F(1,64) =
      21.6, P < .001), and differentiated DLB from AD with sensitivity 73% specificity
      72%. Calculating the topographic expression in an independent data set of 48
      patients with AD and 23 with DLB gave sensitivity = 70%, specificity = 67%.
      Principal component analysis captures additional sources of variance and if
      perfusion SPECT is the only scan available, this procedure may offer extra
      information.

PMID- 20029056
TI  - Medial temporal lobe correlates of memory screening measures in normal aging,
      MCI, and AD.
AB  - This article aimed to study the correlations for both the Memory Impairment
      Screen (MIS) and the Free and Cued Selective Reminding Test (FCSRT) with regard
      to the volumetric measures of hippocampal formation and entorhinal cortex and to
      explore the effect size of these measures. METHODS: A total of 34 healthy
      controls, 24 participants with mild cognitive impairment (MCI), and 20 mild-to
      moderate-staged Alzheimer disease (AD) participants underwent neuropsychological
      testing and magnetic resonance imaging (MRI). Global volumetric measures were
      obtained and hippocampal and entorhinal volumes were calculated. Spearman
      correlations were calculated between memory scores and brain volumes and an
      effect size analysis was performed. RESULTS: No significant correlations with
      global brain volumes were found. There were dissimilar correlations among groups
      regarding memory and hippocampal and entorhinal volumes. No significant
      relationships were observed in healthy controls. The MCI group reached the higher
      correlation indexes, up to r = .55. In AD, only one significant correlation was
      observed between the delayed score of the FCSRT and the left hippocampus. Effect
      size values were higher for memory tests than for MRI measures, reaching d = 4.3
      for the delayed score of the FCSRT. CONCLUSIONS: Although the MIS did not reach
      the strong results of the FCSRT, it demonstrated a similar pattern to the FCSRT
      in correlational analysis. These results support the validity and usefulness of
      the MIS despite its brevity of application. Memory testing showed better
      discrimination among healthy controls, MCI, and AD participants than MRI measures
      by means of effect size analysis.

PMID- 20029057
TI  - Reconsidering the asymptotic null distribution of likelihood ratio tests for
      genetic linkage in multivariate variance components models under complete
      pleiotropy.
AB  - Accurate knowledge of the null distribution of hypothesis tests is important for
      valid application of the tests. In previous papers and software, the asymptotic
      null distribution of likelihood ratio tests for detecting genetic linkage in
      multivariate variance components models has been stated to be a mixture of chi
      square distributions with binomial mixing probabilities. For variance components
      models under the complete pleiotropy assumption, we show by simulation and by
      theoretical arguments based on the geometry of the parameter space that all
      aspects of the previously stated asymptotic null distribution are incorrect-both
      the binomial mixing probabilities and the chi-square components. Correcting the
      null distribution gives more conservative critical values than previously stated,
      yielding P values that can easily be 10 times larger. The true mixing
      probabilities give the highest probability to the case where all variance
      parameters are estimated positive, and the mixing components show severe
      departures from chi-square distributions. Thus, the asymptotic null distribution
      has complex features that raise challenges for the assessment of significance of
      multivariate linkage findings. We propose a method to generate an asymptotic null
      distribution that is much faster than other empirical methods such as
      permutation, enabling us to obtain P values with higher precision more
      efficiently.

PMID- 20029060
TI  - Causal links between binge drinking patterns, unsafe sex and HIV in South Africa:
      its time to intervene.
AB  - South Africa has a massive burden of HIV and alcohol disease, and these pandemics
      are inextricably linked. Much evidence indicates that alcohol independently
      influences decisions around sex, and undermines skills for condom negotiation and
      correct use. Thus, not surprisingly, people with problem drinking in Africa have
      twofold higher risk for HIV than non-drinkers. Also, sexual violence incidents
      often coincide with heavy alcohol use, both among perpetrators and victims.
      Reducing alcohol harms necessitates both population- and individual-level
      interventions, especially raised taxation, regulation of alcohol advertising and
      provision of Brief Interventions. Alcohol counselling interventions must include
      discussion of linkages between alcohol and sex, and consequences thereof. Within
      positive-prevention services, alcohol reduction interventions could diminish HIV
      transmission. A trial is needed to definitively demonstrate that reduced drinking
      lowers HIV incidence. However, given available evidence, implementation of
      effective interventions could alleviate much alcohol-attributable disease,
      including unsafe sex, sexual violence, unintended pregnancy and, likely, HIV
      transmission.

PMID- 20029061
TI  - More than a decade on: review of the use of imiquimod in lower anogenital
      intraepithelial neoplasia.
AB  - To assess the effectiveness of 5% imiquimod cream (IQ) in the treatment of
      vulvar, penile and anal intraepithelial neoplasias (VIN, PIN and AIN), we
      searched Medline, Embase, PubMed and Cochrane Library databases. With regard to
      VIN there were two randomized controlled trials (RCTs), eight uncontrolled/cohort
      studies, nine case reports and one review article. Use of IQ in PIN and AIN were
      only supported by cohort studies (two each for PIN and AIN) and case reports (15
      for PIN and 3 for AIN). On pooled analysis of RCTs, uncontrolled and cohort
      studies, the mean complete response (CR) rate for VIN, PIN and AIN were 51%, 70%
      and 48%, respectively. The mean partial response (PR) rate for VIN, PIN and AIN
      were 25%, 30% and 34% respectively. The recurrence (RR) rate for VIN, PIN and AIN
      were 16%, 0% and 36%, respectively. The follow-up period for VIN, PIN and AIN
      ranged from 2 to 32 months, 10 to 12 months and 11 to 39 months, respectively.
      Although the results for PIN look the best, the strongest evidence regarding
      efficacy of IQ in anogenital intraepithelial neoplasia is for VIN supported by
      RCTs. Evidence for use of IQ in AIN was essentially limited to HIV-positive men
      who have sex with men. IQ was reasonably well tolerated with side-effects being
      managed with reduction in frequency of drug usage and/or rest periods. Based on
      these results, IQ seems to be a safe mode of treatment and is possibly an
      alternative to currently available methods of treatment. However, there are no
      comparative studies assessing its efficacy against traditional modes of
      treatment.

PMID- 20029062
TI  - Characteristics of research-related HIV testing programmes contribute to
      detection of more HIV infections.
AB  - HIV prevalence estimates from bathhouse testing programmes differ widely, ranging
      from 3% to 11%. The observed difference may be a consequence of whether the
      programme was part of a research project or a community-based programme. A
      research-funded testing programme was offered at a bathhouse between May 2001 and
      December 2002. A local community-based organization began a testing programme in
      July 2006 at the same bathhouse; the data for this analysis cover the period July
      2006 through December 2007. County-wide HIV prevalence estimates were available
      across the two time periods (i.e. 2001-2002 and 2006-2007). The research-funded
      testing programme recruited fewer men but identified more positive individuals
      (10.7% of those testing in the research programme) than were identified among men
      who tested in the area clinics (3.8% of those men who have sex with men [MSM]
      testing throughout the county in the same time period). However, the community
      based testing programme identified about the same proportion of positive MSM
      (2.6%) as county clinics (2.7%) in the same time period. In conclusion, results
      confirmed that even in the same venue, a community-based HIV testing programme
      identified a similar proportion of positive MSM as the area clinics; however, the
      research-funded programme identified appreciably more. Incentives may contribute
      to the difference.

PMID- 20029063
TI  - Prevalence of Mycoplasma genitalium among HIV-infected men in Sao Paulo city
      detected by realtime polymerase chain reaction.
AB  - Genital mycoplasmas are natural inhabitants of the male urethra and are
      potentially pathogenic species playing an aetiological role in both genital
      infections and male infertility. This study aims to determine the presence of
      Mycoplasma genitalium DNA in urine samples of HIV-1-infected men in Sao Paulo
      city. Realtime polymerase chain reaction (PCR) was performed using the primers My
      ins and Mgso-2 and the Taqman probe Mgen-P1 as described previously. A total of
      223 HIV-1-infected men were tested with a mean age of 44 years. Thirteen (5.8%)
      presented M. genitalium in urine and the co-infection was more common among
      homosexual men (76.9% versus 51.9%, P < 0.26). In conclusion, realtime PCR was a
      useful and rapid method for detecting M. genitalium DNA in urine samples. Further
      studies should be conducted to assess the clinical significance of these results
      on HIV transmission and its impact on HIV viral load.

PMID- 20029064
TI  - Are primary care-based sexually transmitted infection services in the UK
      delivering public health benefit?
AB  - Sexual health services in primary care, known in the UK as local enhanced
      services in sexual health (LESSH), aim to increase access to sexually transmitted
      infection (STI) screening and treatment. Little is known about the
      characteristics, quality or public health impact of these services. We identified
      national standards for service provision, and evaluated LESSH against them using
      a structure, process and outcome approach. Clinical structure and process
      standards were generally well met, with the exception of partner notification
      provision. However, public health and outcome measures were largely
      unascertainable and often undefined in the standards. If the primary care STI
      services are to deliver public health benefit, improved outcome measures and data
      collection are required.

PMID- 20029065
TI  - Relative efficiency of chlamydia screening in non-clinical settings in two
      California counties.
AB  - We examined the relative efficiency of non-clinical sites to screen for chlamydia
      in youth and young adults. Chlamydia screening targeting youth (under 30 years of
      age) was performed at non-clinical sites in high-morbidity neighbourhoods of two
      California counties. Venues were subdivided into community outreach, schools,
      parenting centres and drug treatment/correctional facilities. Relative efficiency
      was estimated with multivariate Poisson regression using incidence of chlamydia
      per person-hours labour adjusting for strategy and county. Among the 1514 youths
      screened, the overall prevalence of chlamydia was 5.5%. By venue, the highest
      prevalence was in drug treatment/correction facilities at 11.1% followed by
      parenting centres at 6.3%, community outreach at 4.9% and schools at 4.6%. Drug
      treatment/correctional facilities were the most labour time efficient at 9.9
      person-hours per chlamydia case. Schools and parenting centres had the lowest
      cost per screen at 0.9 person-hours per screen. Adjusted relative labour time
      efficiency (chlamydia cases per paid person-hour) was significantly higher in
      schools, 2.0 (95% confidence interval [CI] 1.0-4.2), parenting centres, 3.2 (95%
      CI 1.6-6.6) and drug treatment/correctional facilities, 2.9 (95% CI 1.0-7.8),
      compared with community outreach. In conclusion, parenting centres and drug
      treatment centres and correctional facilities are the most efficient venues for
      chlamydia screening.

PMID- 20029066
TI  - Audit of a sexual health website email link for general practitioners.
AB  - The aim of this review was to evaluate an 'Email a Clinician' link on a medically
      reviewed sexual health website, which was established to allow general
      practitioners (GPs) to communicate remotely with sexual health clinic
      specialists. The website was developed in consultation with GPs and extensively
      promoted throughout the relevant professional primary health-care networks.
      Despite this, the email link appeared to fail in its objective of facilitating GP
      access to specialist sexual health physician opinion within five working days. An
      audit examining use of the email link was conducted for a one-year period, during
      which time 324 emails were received. Results showed that the bulk of the emails
      (93.2%) were spam, and only 6.8% were genuine enquiries. Of the 22 genuine
      emails, 21 (95%) originated from the general public and there were no enquiries
      from the GPs, who were the target audience of the website, resulting in removal
      of the email link from the site. Direct survey of local GPs to evaluate reasons
      for non-utilization of the link was not possible. However, discomfort with the
      technology, time added to existing workload, lack of direct perceived benefit and
      lack of immediate response have been cited as contributing factors that may limit
      widespread adoption of other telemedicine services. As a new generation of
      recently graduated GPs enters the Australian workforce, who might be expected to
      be skilled and comfortable with electronic medical communication, the option of a
      direct email link to a sexual health clinic, with a faster turnaround time, may
      be worth re-visiting in the future.

PMID- 20029067
TI  - Hepatic encephalopathy as an unusual late complication of transjugular
      intrahepatic portosystemic shunt insertion for non-cirrhotic portal hypertension
      caused by nodular regenerative hyperplasia in an HIV-positive patient on highly
      active antiretroviral therapy.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) is an artificially created
      conduit between the portal and systemic vascular system in the liver performed
      percutaneously via radiological guidance. It is used mainly in conditions causing
      portal hypertension and its resulting complications. It reduces portal pressure
      by diverting portal blood flow into the systemic circulation. Hepatic
      encephalopathy is the most common complication following TIPS insertion and tends
      to present fairly early. We describe a case of hepatic encephalopathy as an
      unusual late complication of TIPS insertion (first presenting six years after)
      for non-cirrhotic portal hypertension caused by nodular regenerative hyperplasia
      in an HIV-positive patient on highly active antiretroviral therapy.

PMID- 20029068
TI  - Lack of association between heterosexual lifetime number of sex partners and
      prevalent HIV infection: a crucial implication.

PMID- 20029069
TI  - HIV test result disclosure.

PMID- 20029070
TI  - Charles Darwin (1809-82) and his doctors.

PMID- 20029071
TI  - Giuseppe Pasta (1742-1823): protophysician and pioneer of psychological studies
      in the medical field.
AB  - Giuseppe Pasta was a pioneer of psychological support in physical disease. Born
      in Bergamo, Italy, he was a cousin of the physician Andrea Pasta who was a pupil
      of Giovanni Battista Morgagni. Giuseppe's cultural and clinical resources were
      the teachings of Francesco Redi's medical school in Tuscany. This paper discusses
      the courage and philosophical tolerance of disease and the etiquette of the
      physician.

PMID- 20029072
TI  - The first Charles Darwin (1758-78).
AB  - The paper places the first Charles Darwin in his family context: the eldest son
      of Dr Erasmus Darwin and Mary Howard. Mention is made of Charles's upbringing and
      education, with illustrative material taken from his father's writings and from
      Anna Seward's Memoirs of the Life of Dr Darwin (1804). The part played by Dr
      Andrew Duncan of the Edinburgh Medical School is established. The award to
      Charles in March 1778 of the first medal by the Aesculapian Society of Edinburgh
      is described. The involvement of Dr William Cullen and Dr Joseph Black in the
      treatment of Charles's fatal infection is evidenced from Erasmus' letters.
      Attention is given to 'An Elegy on the much-lamented death of a most ingenious
      young gentleman who lately died in the College at Edinburgh where he was a
      student' which was written jointly by Duncan and Erasmus in 1778. The Elegy's
      curious publishing history will be glanced at. The paper concludes with a
      statement of Charles's great promise as a medical student and of Erasmus' efforts
      to ensure that his son's achievements were memorialised.

PMID- 20029073
TI  - William Somerset Maugham (1874-1966).

PMID- 20029074
TI  - Edward Meryon (1807-80) and Charles Darwin's (1809-82) On the Origin of Species.
AB  - London in the first half of the 19th century was a centre of scientific and
      medical interest. For example, the Royal Society, the Linnean Society, the
      Geological Society, the Chemical Society and the Royal Astronomical Society were
      all centred on Burlington House and, not far away, in Berner's Street was the
      Medical and Chirurgical Society, which in 1834 became the Royal Medical and
      Chirurgical Society and later the Royal Society of Medicine. It was also in this
      period that Edward Meryon became a member of the latter society and subsequently
      a Council Member, Librarian and Vice-President. His research led to the clear
      identification for the first time of the disease Duchenne muscular dystrophy and
      he published his results in the Transactions of the Royal Medical and Chirurgical
      Society in 1852.

PMID- 20029075
TI  - Paget's disease.

PMID- 20029076
TI  - Sarcophilia, cremation and Sir Henry Thompson (1820-1904).
AB  - Sarcophilia, a neologism for an attachment to human remains, is set in a review
      of the history of the disposal of the dead. The ancient practice of cremation was
      relaunched late in the 19th century by the urological surgeon cum social reformer
      Sir Henry Thompson. He was stimulated by Edwin Chadwick and Charles Dickens, and
      by Charles Darwin's observations on the earthworm. Sarcophilia is the reason for
      the controversial Human Tissue Act of 2004.

PMID- 20029077
TI  - John Rae (1813-93): explorer of the Canadian Arctic, the great pedestrian.
AB  - Born and raised in the Orkney Islands, Dr John Rae joined the Hudson's Bay
      Company and rose to be Chief Factor. Unusually tough and intelligent, he explored
      much of northern Canada, mapping the north eastern shore and finding
      controversial evidence of the lost Franklin expedition of 1845. A talented
      botanist, geologist, anthropologist and cartographer, he was northern Canada's
      most distinguished explorer.

PMID- 20029078
TI  - Walcheren 1809.

PMID- 20029079
TI  - Jean Martin Charcot (1825-93) and John Hughlings Jackson (1835-1911): neurology
      in France and England in the 19th century.
AB  - In 1862 Jean Martin Charcot was appointed Physician at the Salpetriere Hospital
      in Paris, and simultaneously John Hughlings Jackson was appointed as assistant
      physician at the National Hospital for the Paralysed and Epileptic, Queen Square,
      London. Both men made significant contributions to the development of neurology,
      many of which remain important to contemporary neurologists. The achievements and
      the work of Charcot and Hughlings Jackson are considered in the light of their
      respective localities and medical education, and the structure of hospital
      institutions and political allegiances are compared in the late 19th century in
      France and Britain.

PMID- 20029081
TI  - Alfred Russel Wallace (1823-1913): evolution and medicine.
AB  - The theory we now know simply as 'evolution' was first presented to the
      scientific world one and a half centuries ago, on 1 July 1858, when the work of
      two men, Alfred Russel Wallace and Charles Robert Darwin (1809-82), was jointly
      read at the Linnean Society. While Charles Darwin has rightly taken his place in
      history as one of the greatest scientists of all time, Alfred Russel Wallace has
      been largely forgotten outside of the scientific community. However, Wallace was
      a prolific researcher and writer with interests in a wide range of topics, from
      medicine to economics.

PMID- 20029083
TI  - Jules Bordet (1870-1961): a bridge between early and modern immunology.
AB  - Jules Bordet, a pioneering immunologist, lived until the dawn of molecular
      immunology. He was born in Belgium in 1870, obtained a medical degree in 1892,
      worked at l'Institut Pasteur in Paris from 1894 to 1901 and then established the
      Pasteur Institute of Brabant in Brussels. Before World War I, Bordet found that
      complement binds to antibody-antigen complexes regardless of the antigen or
      antibodies involved. Subsequently he developed the complement fixation test that
      was of diagnostic importance for several decades. For his research concerning
      complement he was awarded the 1919 Nobel Prize in Physiology or Medicine. During
      that period he also discovered anaphylatoxin, conglutinin, and the cause of
      whooping cough (Bordetella pertussis). After World War I he found how thrombin
      forms, how platelets participate in clotting, lysozyme in human milk and much of
      the biology of bacteriophages. In addition, Bordet worked fervently to limit
      weapons of mass destruction and promote peace until his death in 1961.

PMID- 20029084
TI  - Dr Arnold Renshaw (1885-1980): Manchester pathologist and forensic pathologist
      with a clinical interest in rheumatoid arthritis.
AB  - Dr Arnold Renshaw trained in both dentistry and medicine in Manchester, being
      actively involved in the University student organisations. He followed a career
      in pathology and bacteriology that was interrupted by serving in the RAMC during
      World War I. Bacteriological interest in the antiseptic properties of aniline
      dyes followed. His main interest, however, was in pathology where he was
      associated with the Pathology Society of Manchester for more than twenty years.
      He was also actively involved in the founding of the Association of Clinical
      Pathologists. The Association led to the formation of the Royal College of
      Pathologists and to Renshaw being elected one of the Founding Fellows. He also
      developed a special expertise in forensic pathology which he pioneered in
      northwest England. His later years witnessed an interest in rheumatoid arthritis
      to investigate a possible cause and suggest a unique treatment consisting of the
      small intestinal enzymes, erepsin.

PMID- 20029085
TI  - Did one ear infection in France change the history of Britain? The illness and
      death of Francis II (1544-60).
AB  - The middle ear has long been considered a continuum of the upper respiratory
      tract and modern physicians recognize the impact of upper respiratory tract
      pathology on the middle ear and are familiar with the possible neurosurgical
      complications of any resultant chronic or acute middle ear infection. In the 16th
      century, lack of this knowledge may have led to a sequence of events and one of
      the most important turning points for the British monarchy. This paper on the
      illness and death of King Francis II of France uncovers interesting aspects of
      ENT practice from the French Renaissance period and the intrigue surrounding this
      royal patient's well-documented but little discussed illness.

PMID- 20029086
TI  - The untold neurological disease of Franklin Delano Roosevelt (1882-1945).
AB  - Conventional wisdom suggests that Franklin Delano Roosevelt died on 12 April 1945
      aged 63 from a massive cerebral haemorrhage attributable to uncontrolled
      hypertension and atherosclerosis. Evidence from numerous reliable sources is
      presented, based largely on a constellation of previously unrecognized
      neurological symptoms including seizures, encephalopathy and hemianopia,
      supporting a scenario that, while indeed he suffered from severe cardiovascular
      disease, Roosevelt died from melanoma with the terminal event attributable to a
      metastatic lesion in the brain.

PMID- 20029087
TI  - The emperor Hadrian (fl. AD 117-138) and medicine.

PMID- 20029088
TI  - John Rae (1813-93), Kirkwall, Orkney.

PMID- 20029089
TI  - Re: Where Ronald Ross (1857-1932) worked: the discovery of malarial transmission
      and the Plasmodium life cycle.

PMID- 20029090
TI  - Activation and inhibition of histone deacetylase 8 by monovalent cations.
AB  - The metal-dependent histone deacetylases (HDACs) catalyze hydrolysis of acetyl
      groups from acetyllysine side chains and are targets of cancer therapeutics. Two
      bound monovalent cations (MVCs) of unknown function have been previously observed
      in crystal structures of HDAC8; site 1 is near the active site, whereas site 2 is
      located > 20 A from the catalytic metal ion. Here we demonstrate that one bound
      MVC activates catalytic activity (K(1/2) = 3.4 mM for K(+)), whereas the second,
      weaker-binding MVC (K(1/2) = 26 mM for K(+)) decreases catalytic activity by 11
      fold. The weaker binding MVC also enhances the affinity of the HDAC inhibitor
      suberoylanilide hydroxamic acid by 5-fold. The site 1 MVC is coordinated by the
      side chain of Asp-176 that also forms a hydrogen bond with His-142, one of two
      histidines important for catalytic activity. The D176A and H142A mutants each
      increase the K(1/2) for potassium inhibition by > or = 40-fold, demonstrating
      that the inhibitory cation binds to site 1. Furthermore, the MVC inhibition is
      mediated by His-142, suggesting that this residue is protonated for maximal HDAC8
      activity. Therefore, His-142 functions either as an electrostatic catalyst or a
      general acid. The activating MVC binds in the distal site and causes a time
      dependent increase in activity, suggesting that the site 2 MVC stabilizes an
      active conformation of the enzyme. Sodium binds more weakly to both sites and
      activates HDAC8 to a lesser extent than potassium. Therefore, it is likely that
      potassium is the predominant MVC bound to HDAC8 in vivo.

PMID- 20029091
TI  - Investigations of pi initiator protein-mediated interaction between replication
      origins alpha and gamma of the plasmid R6K.
AB  - A typical plasmid replicon of Escherichia coli, such as ori gamma of R6K,
      contains tandem iterons (iterated initiator protein binding sites), an AT-rich
      region that melts upon initiator-iteron interaction, two binding sites for the
      bacterial initiator protein DnaA, and a binding site for the DNA-bending protein
      IHF. R6K also contains two structurally atypical origins called alpha and beta
      that are located on either side of gamma and contain a single and a half-iteron,
      respectively. Individually, these sites do not bind to initiator protein pi but
      access it by DNA looping-mediated interaction with the seven pi-bound gamma
      iterons. The pi protein exists in 2 interconvertible forms: inert dimers and
      active monomers. Initiator dimers generally function as negative regulators of
      replication by promoting iteron pairing ("handcuffing") between pairs of
      replicons that turn off both origins. Contrary to this existing paradigm, here we
      show that both the dimeric and the monomeric pi are necessary for ori alpha
      driven plasmid maintenance. Furthermore, efficient looping interaction between
      alpha and gamma or between 2 gamma iterons in vitro also required both forms of
      pi. Why does alpha-gamma iteron pairing promote alpha activation rather than
      repression? We show that a weak, transitory alpha-gamma interaction at the iteron
      pairs was essential for alpha-driven plasmid maintenance. Swapping the alpha
      iteron with one of gamma without changing the original sequence context that
      caused enhanced looping in vitro caused a significant inhibition of alpha
      mediated plasmid maintenance. Therefore, the affinity of alpha iteron for pi
      bound gamma and not the sequence context determined whether the origin was
      activated or repressed.

PMID- 20029094
TI  - Effects of Ramadan intermittent fasting on sports performance and training: a
      review.
AB  - The month-long diurnal Ramadan fast imposes a major challenge to Islamic
      athletes. Sporting events are programmed throughout the year, with the result
      that training and competition are often scheduled during Ramadan. The small
      numbers of well-controlled studies that have examined the effects of Ramadan on
      athletic performance suggest that few aspects of physical fitness are negatively
      affected, and only modest decrements are observed. Whereas subjective feelings of
      fatigue and other mood indicators are often cited as implying additional stress
      on the athlete throughout Ramadan, most studies show these measures may not be
      reflected in decreases in performance. The development and early implementation
      of sensible eating and sleeping strategies can greatly alleviate the disruptions
      to training and competitiveness, thus allowing the athlete to perform at a high
      level while undertaking the religious intermittent fast. Nevertheless, further
      research is required to understand the mechanisms and energy pathways that allow
      athletes to maintain their performance capacities during Ramadan, and which
      factors are responsible for the observed decrements in performance of some
      individuals.

PMID- 20029095
TI  - Nocturnal heart rate variability following supramaximal intermittent exercise.
AB  - PURPOSE: To assess the effect of supramaximal intermittent exercise on long-term
      cardiac autonomic activity, inferred from heart rate variability (HRV). METHODS:
      Eleven healthy males performed a series of two consecutive intermittent 15-s runs
      at 95% VIFT (i.e., speed reached at the end of the 30-15 Intermittent Fitness
      Test) interspersed with 15 s of active recovery at 45% VIFT until exhaustion.
      Beat-to-beat intervals were recorded during two consecutive nights (habituation
      night and 1st night) before, 10 min before and immediately after exercise, as
      well as 12 h (2nd night) and 36 h (3rd night) after supramaximal intermittent
      exercise. The HRV indices were calculated from the last 5 min of resting and
      recovery periods, and the first 10 min of the first estimated slow wave sleep
      period. RESULTS: Immediate post-supramaximal exercise vagal-related HRV indices
      were significantly lower than immediate pre-supramaximal exercise values (P <
      .001). Most vagal-related indices were lower during the 2nd night compared with
      the 1st night (eg, mean RR intervals, P = .03). Compared with the 2nd night,
      vagal-related HRV indices were significantly higher during the 3rd night.
      Variables were not different between the 1st and 3rd nights; however, we noted a
      tendency (adjusted effect size, aES) for an increased normalized high-frequency
      component (P = .06 and aES = 0.70) and a tendency toward a decreased low
      frequency component (P = .06 and aES = 0.74). CONCLUSION: Results confirm the
      strong influence of exercise intensity on short- and long-term postexercise heart
      rate variability recovery and might help explain the high efficiency of
      supramaximal training for enhancing indices of cardiorespiratory fitness.

PMID- 20029092
TI  - Interactions of human mismatch repair proteins MutSalpha and MutLalpha with
      proteins of the ATR-Chk1 pathway.
AB  - At clinically relevant doses, chemotherapeutic S(N)1 DNA methylating agents
      induce an ATR-mediated checkpoint response in human cells that is dependent on
      functional MutSalpha and MutLalpha. Deficiency of either mismatch repair activity
      renders cells highly resistant to this class of drug, but the mechanisms linking
      mismatch repair to checkpoint activation have remained elusive. In this study we
      have systematically examined the interactions of human MutSalpha and MutLalpha
      with proteins of the ATR-Chk1 pathway using both nuclear extracts and purified
      proteins. Using nuclear co-immunoprecipitation, we have detected interaction of
      MutSalpha with ATR, TopBP1, Claspin, and Chk1 and interaction of MutLalpha with
      TopBP1 and Claspin. We were unable to detect interaction of MutSalpha or
      MutLalpha with Rad17, Rad9, or replication protein A in the extract system. Use
      of purified proteins confirmed direct interaction of MutSalpha with ATR, TopBP1,
      and Chk1 and of MutLalpha with TopBP1. MutSalpha-Claspin and MutLalpha-Claspin
      interactions were not demonstrable with purified proteins, suggesting that
      extract interactions are indirect or depend on post-translational modification.
      Use of a modified chromatin immunoprecipitation assay showed that proliferating
      cell nuclear antigen, ATR, TopBP1, and Chk1 are recruited to chromatin in a
      MutLalpha- and MutSalpha-dependent fashion after N-methyl-N'-nitro-N
      nitrosoguanidine treatment. However, chromatin enrichment of replication protein
      A, Claspin, Rad17-RFC, and Rad9-Rad1-Hus1 was not detected in these experiments.
      Although our failure to observe enrichment of the latter activities could be due
      to sensitivity limitations, these observations may indicate a novel mechanism for
      ATR activation.

PMID- 20029096
TI  - Training methods and intensity distribution of young world-class rowers.
AB  - PURPOSE: To describe the distribution of exercise types and rowing intensity in
      successful junior rowers and its relation to later senior success. METHODS: 36
      young German male rowers (31 international, 5 national junior finalists; 19.2 +/-
      1.4 y; 10.9 +/- 1.6 training sessions per week) reported the volumes of defined
      exercise and intensity categories in a diary over 37 wk. Training categories were
      analyzed as aggregates over the whole season and also broken down into defined
      training periods. Training organization was compared between juniors who attained
      national and international senior success 3 y later. RESULTS: Total training time
      consisted of 52% rowing, 23% resistance exercise, 17% alternative training, and
      8% warm-up programs. Based on heart rate control, 95% of total rowing was
      performed at intensities corresponding to <2 mmol x L(-1), 2% at 2 to 4 mmol x L(
      1), and 3% at >4 mmol x L(-1) blood lactate. Low-intensity work remained widely
      unchanged at approximately 95% throughout the season. In the competition period,
      the athletes exhibited a shift within <2 mmol exercise toward lower intensity and
      within the remaining approximately 5% of total rowing toward more training near
      maximal oxygen consumption (VO(2max)) intensity. Retrospectively, among subjects
      going on to international success 3 y later had their training differed
      significantly from their peers only in slightly higher volumes at both margins of
      the intensity scope. CONCLUSION: The young world-class rowers monitored here
      exhibit a constant emphasis on low-intensity steady-state rowing exercise, and a
      progressive polarization in the competition period. Possible mechanisms
      underlying a potential association between intensity polarization and later
      success require further investigation.

PMID- 20029097
TI  - Relationship between strength characteristics and unweighted and weighted
      vertical jump height.
AB  - PURPOSE: To investigate the relationship between maximum strength and differences
      in jump height during weighted and unweighted (body weight) static (SJ) and
      countermovement jumps (CMJ). METHODS: Sixty-three collegiate athletes (mean +/-
      SD; age= 19.9 +/- 1.3 y; body mass = 72.9 +/- 19.6 kg; height = 172.8 +/- 7.7 cm)
      performed two trials of the SJ and CMJ with 0 kg and 20 kg on a force plate; and
      two trials of mid-thigh isometric clean pulls in a custom rack over a force plate
      (1000-Hz sampling). Jump height (JH) was calculated from flight time. Force-time
      curve analyses determined the following: isometric peak force (IPF), isometric
      force (IF) at 50, 90, and 250 ms, and isometric rates of force development
      (IRFD). Absolute and allometric scaled forces, [absolute force/(body
      mass(0.67))], were used in correlations. RESULTS: IPF, IRFD, F50(a), F50, F90,
      and F250 showed moderate/strong correlations with SJ and CMJ height percent
      decrease from 0 to 20 kg. IPF(a) and F250(a) showed weak/moderate correlations
      with percent height decrease. Comparing strongest (n = 6) to weakest (n = 6): t
      tests revealed that stronger athletes (IPF(a)) performed superior to weaker
      athletes. CONCLUSION: Data indicate the ability to produce higher peak and
      instantaneous forces and IRFD is related to JH and to smaller differences between
      weighted and unweighted jump heights. Stronger athletes jump higher and show
      smaller decrements in JH with load. A weighted jump may be a practical method of
      assessing relative strength levels.

PMID- 20029098
TI  - Effect of two different training programs with the same workload on soccer
      overhead throwing velocity.
AB  - PURPOSE: The purpose of this study was to determine whether two throwing
      programs, based upon velocity or resistance with the same workload, would enhance
      soccer overhead throwing velocity. METHODS: Sports science students (n = 64, age
      21.1 +/- 2.1 y, mass 71.1 +/- 11 kg, height 1.75 +/- 0.09 m; mean +/- SD) divided
      into two groups matched on performance, participated in the study. The resistance
      training group trained overhead throwing with a 5-kg medicine ball for two sets
      of 8 reps per session, whereas a velocity training group threw four sets of 16
      reps with a regular soccer ball. These training programs were matched on
      workload. Throwing performance with a soccer ball and a 5-kg medicine ball were
      tested before and after a training period of 6 wk with two sessions per week.
      RESULTS: Both groups significantly increased the throwing velocity with the
      soccer ball (resistance-training group: 3.2% [1.0-5.5%]; P = .003 and velocity
      training group: 5.1% [2.6-7.7%]; P < .001), whereas no substantial changes were
      found for throwing with the 5-kg medicine ball after the training period. No
      substantial differences between the groups were found, which indicates that both
      forms of training increased the throwing velocity. CONCLUSIONS: It is concluded
      that both velocity and resistance throwing training programs after a short period
      of training with the same workload can increase throwing velocity and that
      workload is of importance in designing training programs and comparing them with
      each other.

PMID- 20029099
TI  - Physiological responses and perceived exertion during international Taekwondo
      competition.
AB  - PURPOSE: To investigate the physiological responses and perceived exertion during
      international Taekwondo competition. METHODS: Eight male Taekwondo black belts
      (mean +/- SD, age 22 +/- 4 y, body mass 69.4 +/- 13.4 kg, height 1.82 +/- 0.10 m,
      competition experience 9 +/- 5 y) took part in an international-level Taekwondo
      competition. Each combat included three 2-min rounds with 30 s of recovery
      between each round. Heart rate (HR) was recorded at 5-s intervals during each
      combat. Capillary blood lactate samples were taken from the fingertip 1 min
      before competition, directly after each round and 1 min after competition.
      Competitors' rating of perceived exertion (RPE) was recorded for each round using
      Borg's 6-to-20 scale. RESULTS: HR (round 1: 175 +/- 15 to round 3: 187 +/- 8
      beats x min(-1); P < .05), percentage of HR maximum (round 1: 89 +/- 8 to round
      3: 96 +/- 5% HRmax; P < .05), blood lactate (round 1: 7.5 +/- 1.6 to round 3:
      11.9 +/- 2.1 mmol x L(-1); P < .05) and RPE (round 1: 11 +/- 2 to round 3: 14 +/-
      2; P < .05; mean +/- SD) increased significantly across rounds. CONCLUSIONS:
      International-level Taekwondo competition elicited near-maximal cardiovascular
      responses, high blood lactate concentrations, and increases in competitors' RPE
      across combat. Training should therefore include exercise bouts that sufficiently
      stimulate both aerobic and anaerobic metabolism.

PMID- 20029100
TI  - Effects of SAQ training and small-sided games on neuromuscular functioning in
      untrained subjects.
AB  - PURPOSE: The main objective of this study was to investigate the efficacy of both
      programmed (speed, agility, and quickness; SAQ) and random (small-sided games;
      SSG) conditioning methods on selected neuromuscular and physical performance
      variables. METHODS: Twenty volunteers (21.1 +/- 4.0 y, 1.71 +/- 0.09 m, 66.7 +/-
      9.9 kg; mean +/- SD) completed the study. The study design used two physically
      challenging periodized experimental conditions (SAQ and SSG conditions) and a
      nonexercise control condition (CON). Participants engaged in 12.2 +/- 2.1 h of
      directed physical conditioning. All participants had at least 24 h of recovery
      between conditioning sessions, and each 1-h session included 15 min of general
      warm-up and a 45-min exercise session. Participants completed a battery of tests
      (15-m sprint, isokinetic flexion/extension, depth jump) before and following the
      training program. RESULTS: There was a 6.9% (95% CI: -4.4 to 18.3) greater
      improvement in 5-m acceleration time and 4.3% (95% CI: -0.9 to 9.5) in 15-m mean
      running velocity time for the SAQ group compared with the SSG group. In addition,
      increases in maximal isokinetic concentric strength for both the flexor and
      extensor muscles, with the exception of 180 degrees /s flexion, were greater in
      the SAQ than SSG condition. The SAQ group also showed 19.5% (95% CI: -11.2 to
      50.2) greater gain in reactive strength (contact time depth jump) and 53.8% (95%
      CI: 11.2 to 98.6) in mean gastrocnemius medialis activity in comparison with SSG.
      CONCLUSIONS: SAQ training should benefit the physical conditioning programs of
      novice players performing invasion games.

PMID- 20029101
TI  - Development of a simulated round of golf.
AB  - PURPOSE: The aim of this study was to develop a laboratory-based treadmill
      simulation of the on-course physiological demands of an 18-hole round of golf and
      to identify the underlying physiological responses. METHODS: Eight amateur
      golfers completed a round of golf during which heart rate (HR), steps taken, and
      global positioning system (GPS) data were assessed. The GPS data were used to
      create a simulated discontinuous round on a treadmill. Steps taken and HR were
      recorded during the simulated round. RESULTS: During the on-course round, players
      covered a mean (+/-SD) of 8,251 +/- 450 m, taking 12,766 +/- 1,530 steps. The
      mean exercise intensity during the on-course round was 31.4 +/- 9.3% of age
      predicted heart rate reserve (%HRR) or 55.6 +/- 4.4% of age-predicted maximum HR
      (%HRmax). There were no significant differences between the simulated round and
      the on-course round for %HRR (P = .537) or %HRmax (P = .561) over the entire
      round or for each individual hole. Furthermore, there were no significant
      differences between the two rounds for steps taken. Typical error values for
      steps taken, HR, %HRmax, and %HRR were 1,083 steps, +/-7.6 b x min(-1), +/-4.5%,
      and +/-8.1%, respectively. CONCLUSION: Overall, the simulated round of golf
      successfully recreated the demands of an on-course round. This simulated round
      could be used as a research tool to assess the extent of fatigue during a round
      of golf or the impact of various interventions on golfers.

PMID- 20029102
TI  - Effects of shoe cleat position on physiology and performance of competitive
      cyclists.
AB  - PURPOSE: Aerobic economy is an important factor that affects the performance of
      competitive cyclists. It has been suggested that placing the foot more anteriorly
      on the bicycle pedals may improve economy over the traditional foot position by
      improving pedaling efficiency. The current study examines the effects of changing
      the anterior-posterior pedal foot position on the physiology and performance of
      well-trained cyclists. METHODS: In a crossover study, 10 competitive cyclists
      completed two maximal incremental and two submaximal tests in either their
      preferred (control) or a forward (arch) foot position. Maximum oxygen consumption
      and peak power output were determined from the incremental tests for both foot
      positions. On two further occasions, cyclists also completed a two-part 60-min
      submaximal test that required them to maintain a constant power output
      (equivalent to 60% of their incremental peak power) for 30 min, during which
      respiratory and blood lactate samples were taken at predetermined intervals.
      Thereafter, subjects completed a 30-min self-paced maximal effort time trial.
      RESULTS: Relative to the control, the mean changes (+/-90% confidence limits) in
      the arch condition were as follows: maximum oxygen consumption, -0.5% (+/-2.0%);
      incremental peak power output, -0.8% (+/-1.3%); steady-state oxygen consumption
      at 60%, -2.4% (+/-1.1%); steady-state heart rate 60%, 0.4% (+/-1.7%); lactate
      concentration 60%, 8.7% (+/-14.4%); and mean time trial power, -1.5% (+/-2.9%).
      CONCLUSIONS: We conclude that there was no substantial physiological or
      performance advantage in this group using an arch-cleat shoe position in
      comparison with a cyclist's normal preferred condition.

PMID- 20029103
TI  - Oxygen uptake kinetics: an underappreciated determinant of exercise performance.
AB  - The rate at which VO(2) adjusts to the new energy demand following the onset of
      exercise strongly influences the magnitude of the "O(2) deficit" incurred and
      thus the extent to which muscle and systemic homeostasis is perturbed. Moreover,
      during continuous high-intensity exercise, there is a progressive loss of muscle
      contractile efficiency, which is reflected in a "slow component" increase in
      VO(2). The factors that dictate the characteristics of these fast and slow phases
      of the dynamic response of VO(2) following a step change in energy turnover
      remain obscure. However, it is clear that these features of the VO(2) kinetics
      have the potential to influence the rate of muscle fatigue development and,
      therefore, to affect sports performance. This commentary outlines the present
      state of knowledge on the characteristics of, and mechanistic bases to, the VO(2)
      response to exercise of different intensities. Several interventions have been
      reported to speed the early VO(2) kinetics and/or reduce the magnitude of the
      subsequent VO(2) slow component, and the possibility that these might enhance
      exercise performance is discussed.

PMID- 20029104
TI  - Hyperthermic fatigue precedes a rapid reduction in serum sodium in an ironman
      triathlete: a case report.
AB  - PURPOSE: To monitor the hydration, core temperature, and speed (pace) of a
      triathlete performing an Ironman triathlon. METHODS: A 35-year-old experienced
      male triathlete participated in the Western Australian Ironman triathlon on
      December 1, 2006. The participant was monitored for blood Na(+) concentration
      before the race (PRE), at the transitions (T1 and T2), halfway through the run
      (R21), and after the race (POST; 2hPOST). Core body temperature (T(c); pill
      telemetry) was recorded continuously, and running speed (s3 stride sensor) was
      measured during the run. RESULTS: The participant completed the race in 11 h 38
      min, in hot conditions (26.6 +/- 5.8 degrees C; 42 +/- 19% rel. humidity). His
      T(c) increased from 37.0 to 38.6 degrees C during the 57-min swim, and averaged
      38.4 degrees C during the 335-min bike (33.5 km x h(-1)). After running at 12.4
      km x h(-1) for 50 min in the heat (33.1 degrees C), T(c) increased to 39.4
      degrees C, before slowing to 10.0 km x h(-1) for 20 min. T(c) decreased to 38.9
      degrees C until he experienced severe leg cramps, after which speed diminished to
      6 km x h(-1) and T(c) fell to 38.0 degrees C. The athlete's blood Na(+) was
      constant from PRE to T2 (139-140 mEq x L(-1), but fell to 131 mEq x L(-1) at R21,
      133 mEq x L(-1) at POST, and 128 mEq x L(-1) at 2hPOST. The athlete consumed 9.25
      L of fluid from PRE to T2, 6.25 L from T2 to POST, and lost 2% of his body mass,
      indicating sweat losses greater than 15.5 L. CONCLUSION: This athlete slowed
      during the run phase following attainment of a critically high T(c) and
      experienced an unusually rapid reduction in blood Na(+) that preceded cramping,
      despite presenting with signs of dehydration.

PMID- 20029105
TI  - The effect of competition on salivary testosterone in elite female athletes.
AB  - The association between androgens and competition in women has been understudied
      compared with men. The current study examined the link between testosterone (T)
      and competition in elite female athletes, using a sample of female wrestlers that
      included athletes competing at both the national and international level. In a
      repeated-measures design, saliva samples were collected before and after
      wrestling bouts, with comparable samples of wins and losses, and subsequently
      analyzed for T. Study results showed a 22% increase in circulating bioavailable T
      from pre- to postbout, F(1, 12) = 9.71, P = .009. There was no significant
      difference in T between win or loss outcomes. These findings-showing a link
      between individual head-to-head competition and T in women-demonstrate that
      women's androgenic responses to environmental contexts are dynamic and may be an
      important factor to address in research on competitive performance.

PMID- 20029106
TI  - Facing the challenge of biosample imaging by FTIR with a synchrotron radiation
      source.
AB  - Fourier-transform infrared (FTIR) synchrotron radiation (SR) microspectroscopy is
      a powerful molecular probe of biological samples at cellular resolution (<10
      microm). As the brilliance of SR is 100-1000 times higher than that of a
      conventional Globar source, FTIR microscopes are now available in almost all
      advanced SR facilities around the world. However, in spite of this superior
      performance, the expected advances in IR SR microscopy have not yet been
      realised, particularly with regard to bio-analytical studies of single cells and
      soft tissues. In recent decades solid-state array detectors have revolutionized
      the fields of molecular spectroscopy and chemical imaging, and now new IR focal
      plane array detectors implemented at ultra-bright SR facilities will extend the
      performance and overcome the existing limitations, possibly allowing IR SR
      instrumentation to achieve the highest sensitivity and resolution of molecular
      imaging. The impact of IR imaging on large tissue area and the complexity of the
      analysis are discussed. In view of the high brilliance of SR sources, a
      comparison of published microscope images is given. Finally, it is briefly
      outlined how an optimized combination of IR instrumentation and SR optical
      systems could reach the expected advantages of a SR-based FTIR imaging system.

PMID- 20029107
TI  - Temperature gradient analyzers for compact high-resolution X-ray spectrometers.
AB  - Compact high-resolution X-ray spectrometers with a one-dimensional temperature
      gradient at the analyzer crystal are considered. This gradient, combined with the
      use of a position-sensitive detector, makes it possible to relax the usual
      Rowland-circle condition, allowing increased space at the sample position for a
      given energy resolution or arm radius. Thus, for example, it is estimated that
      approximately meV resolution is possible with a 3 m analyzer arm and 200 mm
      clearance between the sample and detector. Simple analytic formulae are provided,
      supported by excellent agreement with ray-tracing simulations. One variation of
      this method also allows the detector position sensitivity to be used to determine
      momentum transfer, effectively improving momentum resolution without reducing
      (slitting down) the analyzer size. Application to medium-resolution (
      approximately 10-100 meV) inelastic X-ray scattering spectrometers with large
      angular acceptance is discussed, where this method also allows increased space at
      the sample. In some cases the application of a temperature gradient can improve
      the energy resolution even with a single-element detector.

PMID- 20029108
TI  - Towards a black-box for biological EXAFS data analysis. II. Automatic BioXAS
      Refinement and Analysis (ABRA).
AB  - In biological systems, X-ray absorption spectroscopy (XAS) can determine
      structural details of metal binding sites with high resolution. Here a method
      enabling an automated analysis of the corresponding EXAFS data is presented,
      utilizing in addition to least-squares refinement the prior knowledge about
      structural details and important fit parameters. A metal binding motif is
      characterized by the type of donor atoms and their bond lengths. These fit
      results are compared by bond valance sum analysis and target distances with
      established structures of metal binding sites. Other parameters such as the Debye
      Waller factor and shift of the Fermi energy provide further insights into the
      quality of a fit. The introduction of mathematical criteria, their combination
      and calibration allows an automated analysis of XAS data as demonstrated for a
      number of examples. This presents a starting point for future applications to all
      kinds of systems studied by XAS and allows the algorithm to be transferred to
      data analysis in other fields.

PMID- 20029109
TI  - Diffractive-refractive optics: low-aberration Bragg-case focusing by precise
      parabolic surfaces.
AB  - Based on analytical formulae calculations and ray-tracing simulations a low
      aberration focal spot with a high demagnification ratio was predicted for a
      diffractive-refractive crystal optics device with parabolic surfaces. Two Si(111)
      crystals with two precise parabolic-shaped grooves have been prepared and
      arranged in a dispersive position (+,-,-,+) with high asymmetry. Experimental
      testing of the device at beamline BM05 at the ESRF provided a focal spot size of
      38.25 microm at a focal distance of 1.4 m for 7.31 keV. This is the first
      experiment with a parabolic-shaped groove; all previous experiments were
      performed with circular grooves which introduced extreme aberration broadening of
      the focal spot. The calculated and simulated focal size was 10.8 microm at a
      distance of 1.1 m at 7.31 keV. It is assumed that the difference between the
      measured and calculated/simulated focal spot size and focal distance is due to
      insufficient surface quality and to alignment imperfection.

PMID- 20029110
TI  - Synergic approach to XAFS analysis for the identification of most probable
      binding motifs for mononuclear zinc sites in metalloproteins.
AB  - In the present work a data analysis approach, based on XAFS data, is proposed for
      the identification of most probable binding motifs of unknown mononuclear zinc
      sites in metalloproteins. This approach combines multiple-scattering EXAFS
      analysis performed within the rigid-body refinement scheme, non-muffin-tin ab
      initio XANES simulations, average structural information on amino acids and metal
      binding clusters provided by the Protein Data Bank, and Debye-Waller factor
      calculations based on density functional theory. The efficiency of the method is
      tested by using three reference zinc proteins for which the local structure
      around the metal is already known from protein crystallography. To show the
      applicability of the present analysis to structures not deposited in the Protein
      Data Bank, the XAFS spectra of six mononuclear zinc binding sites present in
      diverse membrane proteins, for which we have previously proposed the coordinating
      amino acids by applying a similar approach, is also reported. By comparing the Zn
      K-edge XAFS features exhibited by these proteins with those pertaining to the
      reference structures, key spectral characteristics, related to specific binding
      motifs, are observed. These case studies exemplify the combined data analysis
      proposed and further support its validity.

PMID- 20029111
TI  - Characterization of wax as a potential diffraction intensity standard for
      macromolecular crystallography beamlines.
AB  - A number of commercially available waxes in the form of thin disc samples have
      been investigated as possible diffraction intensity standards for macromolecular
      crystallography synchrotron beamlines. Synchrotron X-ray powder diffraction
      measurements show that beeswax offers the best performance of these waxes owing
      to its polycrystallinity. Crystallographic lattice parameters and diffraction
      intensities were examined between 281 and 309 K, and show stable and predictable
      thermal behaviour. Using an X-ray beam of known incident flux at lambda = 1 A,
      the diffraction power of two strong Bragg reflections for beeswax were quantified
      as a function of sample thickness and normalized to 10(10) photons s(-1). To
      demonstrate its feasibility as a diffraction intensity standard, test
      measurements were then performed on a new third-generation macromolecular
      crystallography synchrotron beamline.

PMID- 20029112
TI  - Analysis of tapered front-coupling X-ray waveguides.
AB  - The coupling and propagation of electromagnetic waves through planar X-ray
      waveguides (WG) with vacuum gap and Si claddings are analyzed in detail, starting
      from the source and ending at the detector. The general case of linearly tapered
      WGs (i.e. with the entrance aperture different from the exit one) is considered.
      Different kinds of sources, i.e. synchrotron radiation and laboratory desk-top
      sources, have been considered, with the former providing a fully coherent
      incoming beam and the latter partially coherent beams. It is demonstrated that
      useful information about the parameters of the WG can be derived, comparing
      experimental results with computer simulation based on analytical solutions of
      the Helmholtz equation which take into account the amplitude and phase matching
      between the standing waves created in front of the WG, and the resonance modes
      propagating into the WG.

PMID- 20029113
TI  - Synchrotron-radiation-stimulated etching of polydimethylsiloxane using XeF(2) as
      a reaction gas.
AB  - The synchrotron radiation (SR) stimulated etching of silicon elastomer
      polydimethylsiloxane (PDMS) using XeF(2) as an etching gas has been demonstrated.
      An etching system with differential pumps and two parabolic focusing mirrors was
      constructed to perform the etching. The PDMS was found to be effectively etched
      by the SR irradiation under the XeF(2) gas flow, and the etching process was area
      selective and anisotropic. An extremely high etching rate of 40-50 microm (10
      min)(-1) was easily obtained at an XeF(2) gas pressure of 0.2-0.4 torr. This
      suggests that SR etching using XeF(2) gas provides a new microfabrication
      technology for thick PDMS membranes, which can open new applications such as the
      formation of three-dimensional microfluidic circuits.

PMID- 20029114
TI  - First experiments on the Australian Synchrotron Imaging and Medical beamline,
      including investigations of the effective source size in respect of X-ray
      imaging.
AB  - The Imaging and Medical beamline at the Australian Synchrotron achieved ;first
      light' in December 2008. Here, the first experiments performed on the beamline
      are reported, which involved both X-ray imaging and tomography studies for a
      range of samples. The use of a plastic-edge phantom for quantitative measurements
      of contrast and resolution proved to be very instructive and helped to confirm
      certain parameter values such as the effective horizontal source size, detector
      resolution and average X-ray energy for the polychromatic beam.

PMID- 20029115
TI  - Synchrotron infrared reflectance microspectroscopy study of film formation and
      breakdown on copper.
AB  - This work demonstrates the utility of synchrotron infrared reflectance
      microspectroscopy in the far- and mid-IR for the determination of the composition
      of electrogenerated surface films formed during the general and localized
      corrosion of copper in alkaline and bicarbonate solutions. Back-reflection
      geometry has been employed to identify the anodic film formed on copper in 0.1 M
      NaOH solution at 0.3 V (versus a Ag/AgCl reference) to be mainly CuO. In 0.01 M
      NaHCO(3) solution general corrosion occurs with passive film formation below 0.2
      V. The surface film at 0.2 V consisted mainly of bicarbonate, copper carbonate
      dihydroxide or malachite [CuCO(3).Cu(OH)(2)], Cu(OH)(2) and possibly some CuO. At
      higher potentials the passive film breaks down and localized corrosion occurs
      leading to the formation of pits. The composition of the surface films inside the
      pits formed at 0.6 V was found to be essentially the same as that outside but the
      relative amount of Cu(OH)(2) appears to be higher.

PMID- 20029116
TI  - Artificial neural networks applied to the analysis of synchrotron nuclear
      resonant scattering data.
AB  - The capabilities of artificial neural networks (ANNs) have been investigated for
      the analysis of nuclear resonant scattering (NRS) data obtained at a synchrotron
      source. The major advantage of ANNs over conventional analysis methods is that,
      after an initial training phase, the analysis is fully automatic and practically
      instantaneous, which allows for a direct intervention of the experimentalist on
      site. This is particularly interesting for NRS experiments, where large amounts
      of data are obtained in very short time intervals and where the conventional
      analysis method may become quite time-consuming and complicated. To test the
      capability of ANNs for the automation of the NRS data analysis, a neural network
      was trained and applied to the specific case of an Fe/Cr multilayer. It was shown
      how the hyperfine field parameters of the system could be extracted from the
      experimental NRS spectra. The reliability and accuracy of the ANN was verified by
      comparing the output of the network with the results obtained by conventional
      data analysis.

PMID- 20029117
TI  - Energy-dispersive X-ray absorption spectroscopy at LNLS: investigation on
      strongly correlated metal oxides.
AB  - An energy-dispersive X-ray absorption spectroscopy beamline mainly dedicated to X
      ray magnetic circular dichroism (XMCD) and material science under extreme
      conditions has been implemented in a bending-magnet port at the Brazilian
      Synchrotron Light Laboratory. Here the beamline technical characteristics are
      described, including the most important aspects of the mechanics, optical
      elements and detection set-up. The beamline performance is then illustrated
      through two case studies on strongly correlated transition metal oxides: an XMCD
      insight into the modifications of the magnetic properties of Cr-doped manganites
      and the structural deformation in nickel perovskites under high applied pressure.

PMID- 20029118
TI  - Concept of a spectrometer for resonant inelastic X-ray scattering with parallel
      detection in incoming and outgoing photon energies.
AB  - A spectrometer for resonant inelastic X-ray scattering (RIXS) is proposed where
      imaging and dispersion actions in two orthogonal planes are combined to deliver a
      full two-dimensional map of RIXS intensity in one shot with parallel detection at
      incoming hv(in) and outgoing hv(out) photon energies. Preliminary ray-tracing
      simulations with a typical undulator beamline demonstrate a resolving power well
      above 11000 with both hv(in) and hv(out) near 930 eV, with a vast potential for
      improvement. Combining this instrument - nicknamed hv(2) spectrometer - with an X
      ray free-electron laser source simplifies its technical implementation and
      enables efficient time-resolved RIXS experiments.

PMID- 20029119
TI  - The ID23-2 structural biology microfocus beamline at the ESRF.
AB  - The first phase of the ESRF beamline ID23 to be constructed was ID23-1, a tunable
      MAD-capable beamline which opened to users in early 2004. The second phase of the
      beamline to be constructed is ID23-2, a monochromatic microfocus beamline
      dedicated to macromolecular crystallography experiments. Beamline ID23-2 makes
      use of well characterized optical elements: a single-bounce silicon (111)
      monochromator and two mirrors in Kirkpatrick-Baez geometry to focus the X-ray
      beam. A major design goal of the ID23-2 beamline is to provide a reliable, easy
      to-use and routine microfocus beam. ID23-2 started operation in November 2005, as
      the first beamline dedicated to microfocus macromolecular crystallography. The
      beamline has taken the standard automated ESRF macromolecular crystallography
      environment (both hardware and software), allowing users of ID23-2 to be rapidly
      familiar with the microfocus environment. This paper describes the beamline
      design, the special considerations taken into account given the microfocus beam,
      and summarizes the results of the first years of the beamline operation.

PMID- 20029120
TI  - Development and exploration of a new methodology for the fitting and analysis of
      XAS data.
AB  - A new data analysis methodology for X-ray absorption near-edge spectroscopy
      (XANES) is introduced and tested using several examples. The methodology has been
      implemented within the context of a new Matlab-based program discussed in a
      companion related article [Delgado-Jaime et al. (2010), J. Synchrotron Rad. 17,
      132-137]. The approach makes use of a Monte Carlo search method to seek
      appropriate starting points for a fit model, allowing for the generation of a
      large number of independent fits with minimal user-induced bias. The
      applicability of this methodology is tested using various data sets on the Cl K
      edge XAS data for tetragonal CuCl(4)(2-), a common reference compound used for
      calibration and covalency estimation in M-Cl bonds. A new background model
      function that effectively blends together background profiles with spectral
      features is an important component of the discussed methodology. The development
      of a robust evaluation function to fit multiple-edge data is discussed and the
      implications regarding standard approaches to data analysis are discussed and
      explored within these examples.

PMID- 20029121
TI  - Diffractive-refractive optics: X-ray splitter.
AB  - The possibility of splitting a thin (e.g. undulator) X-ray beam based on
      diffraction-refraction effects is discussed. The beam is diffracted from a
      crystal whose diffracting surface has the shape of a roof with the ridge lying in
      the plane of diffraction. The crystal is cut asymmetrically. One half of the beam
      impinges on the left-hand part of the roof and the other half impinges on the
      right-hand side of the roof. Owing to refraction the left part of the beam is
      deviated to the left whereas the right part is deviated to the right. The device
      proposed consists of two channel-cut crystals with roof-like diffraction
      surfaces; the crystals are set in a dispersive position. The separation of the
      beams after splitting is calculated at a distance of 10 m from the crystals for
      various asymmetry and inclination angles. It is shown that such a splitting may
      be utilized for long beamlines. Advantages and disadvantages of this method are
      discussed.

PMID- 20029122
TI  - Blueprint XAS: a Matlab-based toolbox for the fitting and analysis of XAS
      spectra.
AB  - Blueprint XAS is a new Matlab-based program developed to fit and analyse X-ray
      absorption spectroscopy (XAS) data, most specifically in the near-edge region of
      the spectrum. The program is based on a methodology that introduces a novel
      background model into the complete fit model and that is capable of generating
      any number of independent fits with minimal introduction of user bias [Delgado
      Jaime & Kennepohl (2010), J. Synchrotron Rad. 17, 119-128]. The functions and
      settings on the five panels of its graphical user interface are designed to suit
      the needs of near-edge XAS data analyzers. A batch function allows for the
      setting of multiple jobs to be run with Matlab in the background. A unique
      statistics panel allows the user to analyse a family of independent fits, to
      evaluate fit models and to draw statistically supported conclusions. The version
      introduced here (v0.2) is currently a toolbox for Matlab. Future stand-alone
      versions of the program will also incorporate several other new features to
      create a full package of tools for XAS data processing.

PMID- 20029127
TI  - Dense quasicrystalline tilings by squares and equilateral triangles.
AB  - Dense square-symmetry tilings of the plane by equilateral triangles and squares
      are described. Repeated substitution of a vertex of a tiling by groups of
      vertices leads asymptotically to a limiting density that is independent of the
      starting pattern and to a family of quasicrystalline patterns with 12-fold
      symmetry. Diffraction patterns were computed by treating the vertices as point
      scatterers. As the number of substitutions increases, and as the unit-cell size
      increases, the diffraction patterns from a single unit cell develop a near
      perfect 12-fold symmetry. In addition, the low-intensity background scattering in
      the diffraction patterns exhibits fractal-like self-similar properties, with
      motifs of local intensity recursively decorating the more intense features as the
      number of substitutions progresses.

PMID- 20029128
TI  - Effect of convergent beam semiangle on image intensity in HAADF STEM images.
AB  - In this study, we experimentally and theoretically show that the intensities of
      bright spots in a spherical aberration (C(s))-uncorrected high-angle annular dark
      field (HAADF) scanning transmission electron microscope (STEM) image of [011]
      oriented Co(3)O(4), which has two different numbers of Co atoms in the projected
      atomic columns, are reversed with increasing sample thickness. However, C(s)
      corrected HAADF STEM images produce intensities that correctly depend on the
      average number of atoms in the projected atomic columns. From an analysis based
      on the Bloch-wave theorem, it is found that an insufficient semiangle of the
      incident convergent beam yields intensities that do not depend on the average
      atomic number in the atomic columns.

PMID- 20029129
TI  - A neutron interferometric measurement of a phase shift induced by Laue
      transmission.
AB  - The phenomenon of a neutron phase shift due to Laue transmission in a perfect
      crystal blade is discussed. Quantitative measurements of this phase shift are
      presented in the vicinity of the Bragg condition well in agreement with numerical
      calculations. The phase shift shows a strong angular sensitivity and might
      constitute an interesting opportunity for precision measurements of fundamental
      quantities like the neutron-electron scattering length or gravitational short
      range interactions.

PMID- 20029130
TI  - The long-wavelength limit of the structure factor of amorphous silicon and
      vitreous silica.
AB  - Liquids are in thermal equilibrium and have a non-zero structure factor S(Q -->
      0) = [<N(2)>-<N>(2)]/<N> = rho(0)k(B)Tchi(T) in the long-wavelength limit where
      rho(0) is the number density, T is the temperature, Q is the scattering vector
      and chi(T) is the isothermal compressibility. The first part of this result
      involving the number N (or density) fluctuations is a purely geometrical result
      and does not involve any assumptions about thermal equilibrium or ergodicity, so
      is obeyed by all materials. From a large computer model of amorphous silicon,
      local number fluctuations extrapolate to give S(0) = 0.035 +/- 0.001. The same
      computation on a large model of vitreous silica using only the silicon atoms and
      rescaling the distances gives S(0) = 0.039 +/- 0.001, which suggests that this
      numerical result is robust and perhaps similar for all amorphous tetrahedral
      networks. For vitreous silica, it is found that S(0) = 0.116 +/- 0.003, close to
      the experimental value of S(0) = 0.0900 +/- 0.0048 obtained recently by small
      angle neutron scattering. Further experimental and modeling studies are needed to
      determine the relationship between the fictive temperature and structure.

PMID- 20029131
TI  - Reconstruction from a single diffraction pattern of azimuthally projected
      electron density of molecules aligned parallel to a single axis.
AB  - Diffraction from the individual molecules of a molecular beam, aligned parallel
      to a single axis by a strong electric field or other means, has been proposed as
      a means of structure determination of individual molecules. As in fiber
      diffraction, all the information extractable is contained in a diffraction
      pattern from incidence of the diffracting beam normal to the molecular alignment
      axis. The limited size of the object results in continuous diffraction patterns
      characterized by neither Bragg spots nor layer lines. Equations relating the
      scattered amplitudes to the molecular electron density may be conveniently
      formulated in terms of cylindrical harmonics. For simulated diffraction patterns
      from short C nanotubes aligned along their axes, iterative solution of the
      equation for the zeroth-order cylindrical harmonic and its inverse with
      appropriate constraints in real and reciprocal space enables the phasing of the
      measured amplitudes, and hence a reconstruction of the azimuthal projection of
      the molecule.

PMID- 20029132
TI  - Molecular crystal global phase diagrams. II. Reference lattices.
AB  - In the first part of this series [Keith et al. (2004). Cryst. Growth Des. 4, 1009
      1012; Mettes et al. (2004). Acta Cryst. A60, 621-636], a method was developed for
      constructing global phase diagrams (GPDs) for molecular crystals in which crystal
      structure is presented as a function of intermolecular potential parameters. In
      that work, a face-centered-cubic center-of-mass lattice was arbitrarily adopted
      as a reference state. In part two of the series, experimental crystal structures
      composed of tetrahedral point group molecules are classified to determine what
      fraction of structures are amenable to inclusion in the GPDs and the number of
      reference lattices necessary to span the observed structures. It is found that
      60% of crystal structures composed of molecules with T(d) point-group symmetry
      are amenable and that eight reference lattices are sufficient to span the
      observed structures. Similar results are expected for other cubic point groups.

PMID- 20029133
TI  - Molecular crystal global phase diagrams. III. Sufficient parameter space
      determination.
AB  - In previous parts of this series [Mettes et al. (2004). Acta Cryst. A60, 621-636;
      McClurg & Keith (2010). Acta Cryst. A66, 38-49] a method for constructing global
      phase diagrams (GPDs) for molecular crystals was developed and the method was
      applied to single-component ordered crystal structures of tetrahedral molecules.
      GPDs are useful for visualizing what types of crystal structures a given molecule
      may assume depending on molecular form/interaction. Their construction uses group
      theoretical methods which enumerate all possible symmetry breakings during a
      statistical mechanical high-to-low temperature search. In this work these results
      are expanded upon by outlining a method to determine a sufficiently rich
      parameter space to represent the experimentally observed crystal structures in a
      data set derived from the Cambridge Structural Database. This is significant
      because previous work (Mettes et al., 2004) did not specify the number of
      parameters needed for GPDs. Although there are suggestions in the literature that
      thousands of parameters are required to adequately describe tetrahedral molecule
      intermolecular potentials, it is found that 15 parameters are sufficient to
      represent the structures of the test data. The origin of this difference and its
      implications for determining GPD parameter values from a more detailed
      intermolecular potential and for interpreting GPD parameter values are discussed.

PMID- 20029134
TI  - A new approach to calculating powder diffraction patterns based on the Debye
      scattering equation.
AB  - A new method is defined for the calculation of X-ray and neutron powder
      diffraction patterns from the Debye scattering equation (DSE). Pairwise atomic
      interactions are split into two contributions, the first from lattice-pair
      vectors and the second from cell-pair vectors. Since the frequencies of lattice
      pair vectors can be directly related to crystallite size, application of the DSE
      is thereby extended to crystallites of lengths up to approximately 200 nm. The
      input data correspond to unit-cell parameters, atomic coordinates and
      displacement factors. The calculated diffraction patterns are characterized by
      full backgrounds as well as complete reflection profiles. Four illustrative
      systems are considered: sodium chloride (NaCl), alpha-quartz, monoclinic lead
      zirconate titanate (PZT) and kaolinite. The effects of varying crystallite size
      on diffraction patterns are calculated for NaCl, quartz and kaolinite, and a
      method of modelling static structural disorder is defined for kaolinite. The idea
      of partial diffraction patterns is introduced and a treatment of atomic
      displacement parameters is included. Although the method uses pair distribution
      functions as an intermediate stage, it is anticipated that further progress in
      reducing computational times will be made by proceeding directly from crystal
      structure to diffraction pattern.

PMID- 20029135
TI  - X-ray constrained unrestricted Hartree-Fock and Douglas-Kroll-Hess wavefunctions.
AB  - The extension of the X-ray constrained (XC) wavefunction approach to open-shell
      systems using the unrestricted Hartree-Fock formalism is reported. The XC method
      is also extended to include relativistic effects using the scalar second-order
      Douglas-Kroll-Hess approach. The relativistic effects on the charge and spin
      density on two model compounds containing the copper and iron atom are reported.
      The size of the relativistic effects is investigated in real and reciprocal
      space; in addition, picture-change effects are investigated and discussed for the
      isolated Cu atom. It is found that the relativistic terms lead to changes in the
      densities that are much smaller than those from the X-ray constraint.
      Nevertheless, the use of the relativistic corrections in the ab initio model
      always leads to an improvement in the agreement statistics. An interesting result
      of the unrestricted XC technique is the possibility of obtaining experimentally
      derived spin densities from X-ray data.

PMID- 20029136
TI  - Low-angle scattering by cylindrical structures.
AB  - A theory of diffraction at small angles of scattering by a cylindrically
      constructed structure has been developed and general expressions for two- and
      three-dimensional cylindrically curved crystallites have been obtained. Modified
      expressions have been derived for special cases of (a) a single arc of
      equiangularly spaced identical atoms, (b) several coaxial arcs each having an
      equal number of equiangularly spaced identical atoms and (c) such arcs arranged
      at equal distances along the common axis of the arc, including single cylinders
      and multilayered cylindrical structures. From the expressions obtained, it is
      possible to measure the magnitudes of the radius of the cylinder, the length of
      the cylinder, the angular distance between the scattering atoms on each
      cylindrical arc, their atomic number and the radius of the hole inside each
      cylindrical structure when a particular tube is considered for a particular
      purpose or even when predicting the properties required by a nanotube for a
      particular purpose.

PMID- 20029140
TI  - Treatment of uveitis: beyond steroids.

PMID- 20029141
TI  - Inflammatory choroidal neovascular membrane in posterior uveitis-pathogenesis and
      treatment.
AB  - Choroidal neovascular membrane (CNVM) formation is a well-documented sight
      threatening complication of posterior segment intraocular inflammation (PSII).
      The aim of this article is to review the basic and clinical science literature on
      the pathogenesis of CNVM formation in PSII and to present results of a case
      series. We searched the literature using the mesh terms- inflammation, CNVM, age
      related macular degeneration, immunosuppression, photodynamic therapy, steroids,
      vascular endothelial growth factors and posterior uveitis. Additionally, we
      evaluated the visual outcome of and clinical response to our standard treatment
      protocol involving a combination treatment for young patients with inflammatory
      CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid
      cells as well as choroidal and retinal myeloid cell activation, subsequent
      vascular endothelial growth factors, cytokine and chemokine production and
      complement activation acting in consort to mediate angiogenic responses. No clear
      standard of care currently exists for the treatment of inflammatory CNVM and
      various combinations have been tried. Using our combination treatment, visual
      acuity improved in four, stabilized in one and worsened in four patients. Though
      significant advances have occurred in the understanding of the pathogenesis and
      management of this condition, optimizing therapeutic regimens will require
      further well-constructed prospective cohort series.

PMID- 20029142
TI  - Current approach in diagnosis and management of anterior uveitis.
AB  - Uveitis is composed of a diverse group of disease entities, which in total has
      been estimated to cause approximately 10% of blindness. Uveitis is broadly
      classified into anterior, intermediate, posterior and panuveitis based on the
      anatomical involvement of the eye. Anterior uveitis is, however, the commonest
      form of uveitis with varying incidences reported in worldwide literature.
      Anterior uveitis can be very benign to present with but often can lead to severe
      morbidity if not treated appropriately. The present article will assist
      ophthalmologists in accurately diagnosing anterior uveitis, improving the quality
      of care rendered to patients with anterior uveitis, minimizing the adverse
      effects of anterior uveitis, developing a decision-making strategy for management
      of patients at risk of permanent visual loss from anterior uveitis, informing and
      educating patients and other healthcare practitioners about the visual
      complications, risk factors, and treatment options associated with anterior
      uveitis.

PMID- 20029143
TI  - Intermediate uveitis.
AB  - Intermediate uveitis (IU) is described as inflammation in the anterior vitreous,
      ciliary body and the peripheral retina. In the Standardization of Uveitis
      Nomenclature (SUN) working group's international workshop for reporting clinical
      data the consensus reached was that the term IU should be used for that subset of
      uveitis where the vitreous is the major site of the inflammation and if there is
      an associated infection (for example, Lyme disease) or systemic disease (for
      example, sarcoidosis). The diagnostic term pars planitis should be used only for
      that subset of IU where there is snow bank or snowball formation occurring in the
      absence of an associated infection or systemic disease (that is, "idiopathic").
      This article discusses the clinical features, etiology, pathogenesis,
      investigations and treatment of IU.

PMID- 20029144
TI  - Current approach in the diagnosis and management of posterior uveitis.
AB  - Posterior uveitic entities are varied entities that are infective or non
      infective in etiology. They can affect the adjacent structures such as the
      retina, vitreous, optic nerve head and retinal blood vessels. Thorough clinical
      evaluation gives a clue to the diagnosis while ancillary investigations and
      laboratory tests assist in confirming the diagnosis. Newer evolving techniques in
      the investigations and management have increased the diagnostic yield. In case of
      diagnostic dilemma, intraocular fluid evaluation for polymerase chain testing for
      the genome and antibody testing against the causative agent provide greater
      diagnostic ability.

PMID- 20029145
TI  - Current approach in the diagnosis and management of panuveitis.
AB  - Panuveitis is a generalized inflammation of not only the whole of the uveal tract
      but also involves the retina and vitreous humor. It differs from other anatomical
      sites of inflammation in terms of causes as well as distribution. The common
      causes of panuveitis in our population are tuberculosis, Vogt-Koyanagi-Harada
      syndrome, sympathetic ophthalmia, Behcet's disease and sarcoidosis. A large
      number of cases still remain idiopathic. A stepwise approach is essential while
      evaluating these patients to be able to identify and treat the disease timely and
      correctly. Ancillary tests can be appropriately applied once the anatomic site of
      inflammation is identified. An exhaustive approach comprising a full battery of
      tests is obsolete. Only specific tailored investigations are ordered as suggested
      by the preliminary clinical and ocular examination. The mainstay of the treatment
      of uveitis is corticosteroids. Immunosuppressive agents are administered if the
      inflammation is not adequately controlled with corticosteroids. One of the recent
      breakthroughs in the treatment of refractory uveitis includes the introduction of
      immunomodulating drugs: Tumor necrosis factor-alpha antagonist and Interferon
      alpha. Vitrectomy has been used in uveitis for over a few decades for diagnostic
      and therapeutic purposes. When compared to other anatomical sites of
      inflammation, panuveitis has poor visual outcome due to more widespread
      inflammation. The side-effects of the chronic treatment that these patients
      receive cannot be overlooked and should be specifically monitored under the
      supervision of an internist with special interest in inflammatory diseases.

PMID- 20029146
TI  - Low-dose cyclosporine treatment for sight-threatening uveitis: efficacy,
      toxicity, and tolerance.
AB  - AIM: To ascertain the effectiveness, tolerability, and safety of low-dose
      cyclosporine in the management of sight-threatening uveitis. MATERIALS AND
      METHODS: This was a retrospective clinical case series of patients using oral low
      dose cyclosporine for the management of sight-threatening uveitis in the uvea
      clinic (UC). Patients receiving cyclosporine were identified from the clinic
      database. Main outcome measures were degree of intraocular inflammation, visual
      acuity and dose reduction of oral steroid for effectiveness and adverse symptoms,
      systemic hypertension, and raised serum creatinine for tolerability and safety.
      RESULTS: Intraocular inflammation was improved or stable in 97% of patients,
      visual acuity was improved or stable in 91%, and oral steroid dosage was reduced
      in 73% (by half or more in 51%). Adverse symptoms were almost universal, the
      commonest being peripheral paresthesia/burning in 70% and fatigue in 67%.
      Significant systemic hypertension developed in 27% and raised creatinine in 30%,
      necessitating dose reduction. Cyclosporine was discontinued in 35%, being
      intolerable in 20% and ineffective in 15%. CONCLUSIONS: Cyclosporine was found to
      be effective in reducing inflammation and protecting vision in sight-threatening
      uveitis. It was safe with proper monitoring, including in children. It had a
      significant toxicity profile and a high incidence of adverse symptoms which
      required close supervision, and a prompt dose reduction or drug exchange.

PMID- 20029147
TI  - Pseudo-gonio synechia: an artifact on two-mirror gonioscopy.
AB  - Gonioscopy is an important component of evaluation of any glaucoma patient.
      Goldmann two-mirror and Sussman or Zeiss four-mirror are the commonly used
      gonioscopes. Presence of synechia in the angle is diagnostic of angle closure
      disease in an occludable angle. A patient with pseudo-gonio synechia that
      disappeared on indentation gonioscopy with Sussman lens but persisted with
      manipulation gonioscopy with a Goldmann lens is reported.

PMID- 20029148
TI  - Disseminated orbital actinomycetoma: a case report.
AB  - Mycetoma is a chronic granulomatous infection. Lower extremities are commonly
      involved. A 20-year-old male came with complaints of multiple sinuses on scalp,
      left eyelid swelling with a sinus and dystopia, since one year. On examination
      there was relative proptosis in left eye of 2 mm. Computed tomography scan showed
      soft tissue swelling of the pre-septal area of the left upper eyelid with orbital
      involvement. Magnetic resonance imaging showed increased left orbital volume and
      evident dystopia. Microbiology testing of the erosive scalp and lid lesions
      showed genus Nocardia, suggestive of actinomycetoma. This case is presented as it
      shows an unusual involvement of the orbit.

PMID- 20029149
TI  - Coin-shaped epithelial lesions following an acute attack of erythema multiforme
      minor with confocal microscopy findings.
AB  - We report an interesting ocular finding of bilateral multiple coin-shaped
      epithelial lesions along with the confocal microscopy findings in a patient
      following an acute attack of erythema multiforme (EM) minor. A 30-year-old male
      presented with a history of watering and irritation in both eyes of three days
      duration. He was diagnosed to have EM minor and was on oral acyclovir. Slit-lamp
      examination revealed multiple coin-shaped epithelial lesions. Confocal microscopy
      showed a corresponding conglomerate of hyper-reflective epithelial lesions. The
      corneal lesions resolved over six weeks with oral steroids and acyclovir. An
      immunological mechanism is suspected.

PMID- 20029150
TI  - Isolated trochlear nerve palsy with midbrain hemorrhage.
AB  - Midbrain hemorrhage causing isolated fourth nerve palsy is extremely rare.
      Idiopathic, traumatic and congenital abnormalities are the most common causes of
      fourth nerve palsy. We report acute isolated fourth nerve palsy in an 18-year-old
      lady due to a midbrain hemorrhage probably due to a midbrain cavernoma. The case
      highlights the need for neuroimaging in selected cases of isolated trochlear
      nerve palsy.

PMID- 20029151
TI  - Clear lens extraction and intraocular lens implantation in a case of
      microspherophakia with secondary angle closure glaucoma.
AB  - Phacoemulsification with implantation of single-piece acrylic foldable
      intraocular lens (IOL) in a 19-year-old boy with microspherophakia, high myopia
      and angle closure glaucoma is described. The associated myopia and angle closure
      glaucoma was severely compromising the quality of life. Post-surgical visual
      recovery was 20/20 with sustained normal intraocular pressure. Management of such
      cases at times calls for innovations in current surgical technique.

PMID- 20029152
TI  - Intravitreal cysticercosis presenting as neovascular glaucoma.
AB  - We report two cases of intraocular cysticercosis which showed a peculiar
      presentation of neovascular glaucoma which is hitherto unreported. Two young
      adults presented with symptoms of raised intraocular pressure due to neovascular
      glaucoma. On dilated fundus examination both were found to have dead intravitreal
      cysticercosis. The cysts were removed by a three-port vitrectomy and intracameral
      injection of bevacizumab was given to help in the regression of rubeosis.
      Trabeculectomy had to be combined in one case. The intraocular pressure returned
      to normal. No recurrence of rubeosis was seen even after one year.

PMID- 20029153
TI  - Verteporfin photodynamic therapy of retinal capillary hemangioblastoma in von
      Hippel-Lindau disease.
AB  - An 18-year-old boy presented to us with bilateral retinal hemangioblastoma and
      von Hippel-Lindau disease with history of cerebral capillary hemangioblastoma and
      embryonic cell carcinoma of left testes. The vision in the right eye was already
      lost with development of secondary closed angle glaucoma, optic atrophy with
      subsequent development of bullous keratopathy. The multiple retinal angiomatous
      lesions in the seeing left eye were treated with various modalities like triple
      freeze thaw cryopexy, focal lasers and transpupillary thermo therapy in multiple
      sittings over a period of almost 20 years since detection. One particular
      angiomatous lesion in the left eye was showing resistance to all the above
      mentioned modalities and was finally successfully treated with verteporfin and
      photodynamic therapy to achieve complete regression without any post-treatment
      complication and with a sustained 20/20 vision till a follow-up of 15 months.

PMID- 20029155
TI  - Melkersson-Rosenthal syndrome in a patient with tubercular panuveitis.
AB  - We report a rare presentation of Melkersson-Rosenthal syndrome in a patient with
      tubercular panuveitis. A 45-year-old male being treated with antitubercular
      therapy for tubercular panuveitis presented with unilateral, non-pitting right
      upper eyelid edema. Excision biopsy showed granulomatous inflammation involving
      the lymphatics. Immunohistochemistry confirmed the presence of histiocytes around
      the lymphatics.

PMID- 20029154
TI  - Intravitreal anti-vascular endothelial growth factor agents as an adjunct in the
      management of Coats' disease in children.
AB  - We describe the role of intravitreal anti-vascular endothelial growth factor
      (VEGF) agents in Coats' disease in children. In a prospective, interventional,
      non-randomized case series, three patients (three eyes) aged 16, seven and two
      years were diagnosed to have Coats' disease. In Case 1 (16 yr/ male) with macular
      edema, previous laser photocoagulation being unsuccessful, intravitreal
      pegaptanib sodium (Macugen) was tried. Case 2 (seven yr/ male) and Case 3 (two
      yr/ female) were diagnosed to have Stage 4 Coats' and underwent external needle
      drainage, laser photocoagulation, SF6 gas injection and intravitreal injection of
      bevacizumab (Avastin). Reduction of exudation and attached posterior pole (Cases
      2 and 3) was seen at a follow-up of six months and two months respectively.
      Intravitreal anti-VEGF agents may be successfully used as adjunct treatment in
      select cases of Coats' disease in childhood.

PMID- 20029156
TI  - Resolution of macular edema in Coats' disease with intravitreal bevacizumab.
AB  - A 13-year-old boy was referred because of visual deterioration in his right eye.
      The visual acuity was two meters of counting fingers. Indirect ophthalmoscopy and
      biomicroscopy revealed exudative macular edema as well as tumor-like
      telangiectatic vessels and exudation in temporal periphery. With diagnosis of
      Coats' disease (stage II) confirmed by fluorescein angiography, three
      intravitreal injections of bevacizumab were performed at 6-week intervals. One
      year after the last injection, there was a significant resolution of macular
      edema as well as visual acuity improvement to 20/20. This is the first case
      report in which a distinct improvement in macular edema was observed with
      intravitreal bevacizumab in Coats' disease.

PMID- 20029157
TI  - Intracameral use of 2% lignocaine with preservative: is it really safe?

PMID- 20029158
TI  - Evaluation of medical college departments of ophthalmology in India.

PMID- 20029159
TI  - Nucleus management with Blumenthal technique: anterior chamber maintainer.

PMID- 20029160
TI  - Wound construction in manual small incision cataract surgery.

PMID- 20029161
TI  - Modified "temporal" sutureless vitrectomy.

PMID- 20029162
TI  - Blumenthal technique and its modification: the glory of anterior chamber
      maintainer.

PMID- 20029163
TI  - Clinicopathological study of 13 cases of squamous cell carcinoma complicating
      hidradenitis suppurativa.
AB  - BACKGROUND: To the best of our knowledge, only 52 cases of squamous cell
      carcinoma (SCC) complicating hidradenitis suppurativa (HS) have been reported
      since 1958. We describe 13 new cases. METHODS: We propose a clinical and
      histological analysis of our cases. We include these results in a review of
      previously reported cases to analyze a total of 65 patients. In our series of 13
      cases, we also investigate the presence of human papillomavirus (HPV) in tumor
      samples, by polymerase chain reaction (PCR) on paraffin-embedded material.
      RESULTS: Malignant transformation affects mainly men with a long-term history of
      genitoanal HS. Although our cases were 7 well-differentiated carcinomas and 6
      verrucous carcinomas, lymphatic and visceral metastasis occurred in 2 and 3
      cases, respectively. With PCR, we demonstrated presence of HPV in genitoanal
      tumoral lesions, principally HPV-16. CONCLUSION: SCC complicating HS evolves
      poorly, despite a good histological prognosis. Our results sustain the
      implication of HPV in the malignant transformation of HS.

PMID- 20029164
TI  - Disseminated cutaneous lymphoid hyperplasia of 12 years' duration triggered by
      vaccination.
AB  - Vaccine-induced cutaneous lymphoid hyperplasia (CLH) is rare. Its natural
      evolution is not well known, nor is its treatment. We report a case of B-cell CLH
      with secondary dissemination that occurred following vaccination. The symptoms
      lasted 12 years and were efficiently treated by thalidomide. A 17-year-old girl
      presented CLH which had begun at the age of 8 at the site of hepatitis B
      vaccination. The lesions progressively enlarged and disseminated far from the
      injection sites. There was no spontaneous remission. Cyclins and
      hydroxychloroquine were inefficient. Thalidomide treatment finally led to
      complete remission. Aluminium hydroxide is used as adjuvant in the majority of
      vaccinations. In this case, occurrence of lesions far from the injection site of
      the vaccine suggested that it was not the only cause and that CLH may occur in
      other localizations after a vaccination. Furthermore, the diagnosis of CLH should
      not be excluded in front of such a prolonged course, and we underline the
      potential efficacy of thalidomide.

PMID- 20029165
TI  - Coupling aging immunity with a sedentary lifestyle: has the damage already been
      done?--a mini-review.
AB  - The elderly population is at an unprecedented risk of infectious diseases and
      malignancy due to apparently inevitable age-related declines in immunity. The
      'immune risk profile' (IRP) is an array of biomarkers that has been used to
      predict morbidity and mortality in older adults. As it is generally accepted that
      middle-aged and elderly individuals who habitually participate in moderate
      intensity exercise are less likely to incur an infection than their sedentary
      counterparts, this review addresses current knowledge on the effects of regular
      exercise on aspects of adaptive immunity as they relate to the IRP. Findings from
      cross-sectional studies mostly show enhanced immunity in physically active
      compared to sedentary older adults. These include greater T-cell responsiveness
      to mitogens in vitro, a reduced frequency of antigen-experienced and senescent T
      cells (i.e. CD45RO+/KLRG1+/CD57+/CD28-), enhanced IL-2 production and T
      lymphocyte expression of the IL-2 receptor, longer chromosome telomere lengths in
      blood leukocytes and in vivo immune responses to vaccines and recall antigens. In
      contrast, the evidence from the available longitudinal studies that have used an
      exercise training intervention in previously sedentary elderly to improve similar
      immune responses is less compelling. Although this might indicate that exercise
      has limited immune restorative properties in previously sedentary elderly, there
      are still relatively few studies that have addressed specific IRP criteria and
      the large variation in experimental design among the longitudinal studies
      complicates the juxtaposition of these results. It is clear that a more
      substantial and focused research approach is required before physical exercise
      can be used in earnest as an effective immune restorative strategy in the
      elderly. This mini-review summarizes the major findings of these studies and
      proposes future avenues of research to investigate the effects of regular
      exercise on aspects of adaptive immunity in the elderly as they relate to the
      IRP.

PMID- 20029166
TI  - Residual pleural thickening is related to vascular endothelial growth factor
      levels in parapneumonic pleural effusions.
AB  - BACKGROUND: Many patients with pneumonia develop pleural effusions. Pleural fluid
      vascular endothelial growth factor (VEGF) levels are known to be elevated in
      complicated parapneumonic effusion and seem to play a major role in the fibrotic
      process in the pleura. OBJECTIVES: To test whether VEGF levels in pleural
      effusions of infectious origin correlate with the residual pleural thickening.
      METHODS: VEGF levels were measured in the pleural fluid of 45 patients with
      pleural effusion of infectious origin. Patients were reassessed 3 months after
      hospital discharge and residual pleural thickening (RPT) was recorded using a
      simple chest radiograph. RESULTS: Pleural fluid VEGF was higher in empyemas
      compared to simple parapneumonic and complicated parapneumonic effusions. RPT was
      higher in patients with empyemas compared to simple parapneumonic effusions.
      Patients with RPT >2 mm had higher pleural fluid LDH and pleural fluid to serum
      LDH ratio, lower glucose and pH and higher VEGF levels. However, patients with
      RPT >=10 mm differed only in pleural fluid VEGF levels. Pleural fluid VEGF levels
      correlated to RPT and to pleural fluid pH. VEGF presented moderate performance
      for the prediction of RPT 3 months after hospital discharge. Its performance was
      comparable to that of pleural fluid glucose and pH for the development of a
      radiologically significant RPT >2 mm, whereas it was the only statistically
      significant predictor of a clinically significant RPT >=10 mm. CONCLUSION: VEGF
      levels are elevated in complicated parapneumonic effusions and empyemas compared
      to simple parapneumonic effusions and are a significant predictor for the
      development of clinically significant RPT.

PMID- 20029167
TI  - First case of a neocentromere formation in an otherwise normal chromosome 7.
AB  - According to cytogenetic and molecular cytogenetic characterization, an otherwise
      not-altered chromosome 7 formed a neocentromere in band 7q32.1 in a clinically
      normal female. The alpha satellite sequence D7Z1 remained in its place but was
      not used for formation of the primary chromosomal incision. Similar observations
      of centromere repositioning have been made for chromosomes 3 (2x), 4, 8 and Y
      (2x). Even though data is available for some neocentromeres whose positions are
      correlated with evolutionary new centromeres for 7q32.1, no correlation could be
      found for an ancestral inactivated centromere in any of the presently living
      primates. Overall, we report a new case of centromere repositioning at a position
      not known to harbor an ancestral inactivated centromere.

PMID- 20029168
TI  - Nurse-administered propofol sedation: feasibility and safety in bronchoscopy.
AB  - BACKGROUND: Propofol is a fast-acting intravenous sedative that has advantages as
      a procedural sedative over traditional regimens. It has been shown to have a
      similar safety profile to traditional sedating medications in the setting of
      gastroenterologic endoscopy. Nurse-administered propofol sedation is given by a
      specially-trained nurse, without anesthesiologist involvement. OBJECTIVES: We
      have used nurse-administered propofol sedation in our bronchoscopy suite for
      several years. In this report, we summarize our experience with nurse
      administered propofol sedation, and demonstrate it to be feasible and safe for
      bronchoscopic procedures. METHODS: Procedure reports and nursing notes for 588
      bronchoscopic procedures performed between July 2006 and June 2008 were
      retrospectively reviewed. Patient demographics, procedure type and indication,
      procedure time, medication doses, and adverse events were noted and analyzed.
      RESULTS: Nurse-administered propofol sedation was used in 498/588 (85%)
      procedures. Patients utilizing nurse-administered propofol sedation had an
      average age of 53 years (range 18-86) with an average weight of 80 kg. 56% of the
      patients were male, and 57% of the procedures were performed on outpatients.
      Average procedure duration was 25 min (range 3-123). The average propofol dose
      was 3.13 mg/kg (range 0.12-20 mg/kg). Adverse events attributable to sedation
      were noted in 33 (6.6%) procedures. Of the 14 (2.8%) major adverse events (death,
      need for intubation, ICU stay, or hospitalization), only 6 (1.2%) were
      potentially attributable to the sedation regimen. There were 2 deaths, neither of
      which was related to sedation. CONCLUSIONS: Nurse-administered propofol sedation
      is a feasible and safe sedation method for bronchoscopic procedures.

PMID- 20029170
TI  - Response to spray cryotherapy in a patient with adenocarcinoma in the parietal
      pleura.
AB  - Malignancies of the parietal pleura, whether primary or metastatic, are a
      therapeutic challenge, and current therapies target their symptoms and not their
      tumor burden. Therefore, alternatives to standard approaches seem warranted. A
      patient with a parietal pleura-based adenocarcinoma was treated with low-pressure
      spray cryotherapy after failing more traditional approaches. The patient
      underwent therapeutic pleuroscopy with moderate sedation and local analgesia of
      the right chest. She was treated with the CSA Medical spray cryotherapy system,
      which was introduced into the chest via the working channel of a semi-rigid
      pleuroscope. Pleuroscopic examination 3 days after spray cryotherapy revealed
      >50% reduction in tumor size. No adverse events or complications occurred as a
      result of treatment. At the 3-month follow-up, a slightly raised mound of tissue
      was noted at the treatment site. This area was biopsied and found to be negative
      for tumor, containing only chronic inflammatory tissue. No evidence of residual
      cancer was observed. Initial observations include lack of a bystander effect on
      lung and pleura; no significant side effects or symptoms; a 50% tumoricidal
      response 3 days after treatment, and a complete tumoricidal response 90 days
      after treatment without evidence of tumor on the parietal pleura.

PMID- 20029169
TI  - Novel method to process cystic fibrosis sputum for determination of oxidative
      state.
AB  - BACKGROUND: Induced sputum is the most commonly used method to analyze airway
      inflammation in cystic fibrosis (CF) patients ex vivo. Due to the complex matrix
      of the sample material, precise and reliable analysis of sputum constituents
      depends critically on preanalytical issues. OBJECTIVES: Here we compared the
      commonly used method for sputum processing by dithiothreitol (DTT) with a novel
      mechanical method in regard to basal cellular parameters, neutrophil markers and
      glutathione (GSH) levels. METHODS: Sputum samples from CF patients were processed
      in parallel with or without the use of DTT. The key improvement of the mechanical
      method was the processing in many very small aliquots. Cellular and humoral
      markers were assessed and compared according to Bland-Altman. RESULTS: Total cell
      count, cell viability, differential cell count, neutrophil elastase levels and
      flow cytometrically analyzed neutrophil markers (CD63, CD11b, DHR) did not differ
      between the two methods. Intracellular and extracellular GSH levels were
      significantly higher in DTT-treated samples (p = 0.002). CONCLUSION: The
      mechanical sputum-processing method presented had a similar yield of cells and
      fluids as the conventional DTT method and the advantage of omitting the
      introduction of reducing agents. This method allows a more reliable analysis of
      redox-dependent airway inflammation in sputum cells and fluid from CF patients
      than methods utilizing DTT.

PMID- 20029171
TI  - Concurrent and apposed hepatocellular carcinoma and small lymphocytic
      lymphoma/chronic lymphocytic leukemia in a patient with hepatitis C virus.
AB  - A patient with chronic hepatitis C virus (HCV) presented to our clinic with a
      hepatic mass as well as lymphocytosis. Biopsy of the hepatic mass revealed
      apposed hepatocellular carcinoma (HCC) and small lymphocytic lymphoma
      (SLL)/chronic lymphocytic leukemia (CLL). Dramatic examples of lymphoma
      regression during treatment with antiviral medication in chronic HCV patients
      have suggested an etiologic role for HCV in lymphomagenesis. A growing body of
      research seeks to clarify the details of the interaction between HCV and B-cell
      lymphomas. This case of adjacent SLL/CLL and HCC is the first published diagnosis
      of these two diseases in the liver at one time, and the only published example of
      the physical apposition of any lymphoma and HCC. The case is provocative in light
      of recent evidence that local interactions between HCV-infected hepatocytes and B
      cells may contribute to lymphomagenesis.

PMID- 20029172
TI  - Erythropoietin and cyclophosphamide combination treatment additively enhances
      antibody production in mice.

PMID- 20029173
TI  - Vascular endothelial growth factor polymorphisms in mantle cell lymphoma.
AB  - In this study, we determined the allele and genotype frequencies of vascular
      endothelial growth factor (VEGF) G+405C, C-460T, C+936T and C-2578A single
      nucleotide polymorphisms (SNPs) in 32 patients affected by mantle cell lymphoma
      (MCL) and 58 healthy controls. Real-time PCR combined with melting curve analysis
      was used for the determination of SNP alleles. A significant difference in the
      allele frequency of VEGFC-460T and C+936T SNPs in MCL and healthy cases was not
      observed. On the contrary, VEGF G+405C and C-2578A SNP allele distribution was
      significantly lower in the patient group than among normal controls (p = 0.014, p
      = 0.001). This observation suggests that further investigation is warranted, both
      in vitro and in a larger series of patients, to further examine the role of VEGF
      polymorphisms in the pathogenesis of MCL. In addition, the use of quantitative
      real-time PCR combined with a melting curve analysis method in the detection of
      the 4 VEGF SNPs may have the potential to replace older and more time-consuming
      PCR-RFLP methods and bears further investigation.

PMID- 20029174
TI  - Management of chronic childhood immune thrombocytopenic purpura: AIEOP consensus
      guidelines.
AB  - BACKGROUND/OBJECTIVE: The management of chronic childhood idiopathic
      thrombocytopenic purpura (ITP) is distinct from acute ITP. Similar to the
      publication on acute ITP guidelines, the AIEOP (Associazione Italiana di
      Ematologia e Oncologia Pediatrica) considered it appropriate to develop consensus
      guidelines for chronic childhood ITP to provide useful and shared information for
      physicians, healthcare professionals, parents and patients. DESIGN/METHODS: A
      preliminary, evidence-based document issued by a select group of AIEOP pediatric
      hematologists was discussed, modified and approved during a Consensus Conference
      according to procedures previously validated by the AIEOP Board. RESULTS: The
      guidelines give prominence to the periodical reevaluation of all the etiological
      hypotheses of thrombocytopenia in relation to its clinical condition. The
      majority of chronic ITP children do not require treatment, especially if bleeding
      is absent or minimal. The treatment decision depends on several factors other
      than the platelet count, and treatment options are suggested in relation to the
      therapeutic scenarios. Recommendations are given regarding support for surgery,
      particular hemorrhagic conditions, daily activities/sports, as well as for
      vaccines and drugs. Experimental treatments are also discussed.

PMID- 20029175
TI  - Mechanisms and control of protein translation in the kidney.
AB  - Translational control of protein synthesis is critical for cell division,
      homeostasis and survival. Recent data indicate that dysregulation of protein
      synthesis that leads to either increased or decreased expression of specific
      proteins contributes to the manifestations of various kidney diseases. Most of
      the control of protein synthesis occurs in the first or initiation phase, which
      is also the most complicated. Following the initiation phase is the elongation
      phase where the peptide chain is formed. RNA transcripts are released from
      ribosomes after the termination phase. Transcripts can be translated in a cap
      dependent or cap-independent manner. The mTOR (mammalian target of rapamycin)
      cascade regulates translation of most cap-dependent transcripts at the level of
      initiation and elongation, which represents 95% of total transcripts. During
      specific events (e.g. mitosis, stress cell survival) control of the less-common
      cap-independent transcripts occurs which allows the cell to adapt to the new
      state. Activation of stress kinases and inactivation of the mTOR pathway are at
      the center of this adaptive mechanism. Recent studies have elucidated the role of
      micro-RNAs (miRs) in controlling translation. miRs bind directly to specific
      transcripts and most often directly reduce translation; however, by targeting
      other positive or negative regulators of the pathways regulating protein
      synthesis they may indirectly affect synthetic levels of other transcripts.
      Several examples are described below in which these mechanisms are intertwined
      and act together to dysregulate protein synthesis in the diseased kidney.

PMID- 20029177
TI  - Use of body surface area for assessing extracellular fluid volume and glomerular
      filtration rate in obesity.
AB  - OBJECTIVE: To examine body surface area (BSA) for scaling extracellular fluid
      volume (ECV) in obesity. ECV varies less than glomerular filtration rate (GFR) in
      a clinical population and was therefore used as a surrogate for GFR on the
      grounds that if BSA is unsuitable for scaling GFR, it will also be unsuitable for
      ECV. METHODS: GFR was measured in 917 patients using (51)Cr-EDTA. GFR scaled to
      ECV was measured exclusively from the slope rate constant. ECV was calculated as
      GFR divided by GFR/ECV. RESULTS: BSA correlated strongly with body mass index
      (BMI). ECV correlated strongly with BSA but the intercept was significantly lower
      than zero, indicating a disproportionate relation. ECV/BSA correlated with BSA
      but not with BMI. ECV in obese subjects was significantly less than in non-obese
      subjects individually matched for BSA. ECV/BSA was similar between obese and lean
      subjects matched for GFR/ECV and height. CONCLUSIONS: For subjects of similar
      BSA, a high BMI decreases ECV (the 'obesity effect'). Subjects with high BMI
      generally have high BSA, which tends to increase ECV/BSA because of the
      disproportionate relation between ECV and BSA (the 'BSA effect'). These opposing
      effects serendipitously and erroneously create the impression that BSA is
      suitable for scaling ECV (and by implication, GFR) in obesity.

PMID- 20029176
TI  - The Association of African Ancestry and elevated creatinine in the Coronary
      Artery Risk Development in Young Adults (CARDIA) Study.
AB  - Whether genetic factors account for differences in early kidney disease among
      blacks in a young healthy population is not well known. We evaluated the
      association of self-reported race and genetic African ancestry with elevated
      creatinine (> or =1.3 mg/dl for men, > or =1.1 mg/dl for women) among 3,113 black
      and white participants in the Coronary Artery Risk Development in Young Adults
      (CARDIA) study, ages 38-50 years. We estimated individual African ancestry using
      42 ancestry informative markers. Blacks were more likely to have elevated
      creatinine than whites, and this effect was more pronounced in men: adjusted odds
      ratio (AOR) for black versus white men = 7.03, 4.15-11.91; AOR for women = 2.40,
      1.15-5.02. Higher African ancestry was independently associated with elevated
      creatinine among black men (AOR = 1.53,1.08-2.16 per SD increase in African
      ancestry), but not women. A graded increase in odds of elevated creatinine by
      African Ancestry was observed among black men compared with white men: AOR = 4.27
      (2.26-10.06) for black men with 40-70% African ancestry; AOR = 8.09 (4.19-15.61)
      for black men with 70-80% African ancestry; AOR = 9.05 (4.81-17.02) for black men
      with >80% African ancestry. Genetic factors common to African ancestry may be
      associated with increased risk of early kidney dysfunction in a young, healthy
      population, particularly among black men.

PMID- 20029178
TI  - Glutathione s-transferase m1 and t1 polymorphisms and susceptibility to oxidative
      damage in healthy korean smokers.
AB  - AIMS: The relationship between glutathione S-transferase (GST) polymorphisms and
      susceptibility to smoking-induced oxidative damage was investigated in healthy
      Korean smokers. METHODS: Forty-nine healthy male smokers (20-59 years)
      participated in the study. GSTT1 and GSTM1 genotypes were determined, and
      lymphocyte DNA damage was assessed by the Comet assay. RESULTS: Out of the 49
      smokers, 20 individuals were GSTT1 positive and 29 were GSTT1 null. For GSTM1, 45
      smokers were GSTM1 positive and 4 were GSTM1 null. HDL cholesterol levels (p =
      0.011) and the atherogenic index of plasma (p = 0.01) were significantly reduced,
      and concentrations of conjugated dienes were increased (p = 0.01) in the GSTT1
      null individuals but not in the GSTT1-positive individuals. The GSTT1-null
      individuals were more susceptible to DNA damage than the GSTT1-positive
      individuals. For all parameters, the GSTM1 genotypes were excluded from
      statistical analyses due to the small number of subjects with the GSTM1-null
      type. CONCLUSIONS: Our findings suggest that subjects with the GSTT1-null
      genotype were more susceptible to oxidative damage than the GSTT1-positive
      subjects. Therefore, the GSTT1-null genotype may confer an increased risk of
      smoking-related cardiovascular disease.

PMID- 20029179
TI  - Association of a common G6PC2 variant with fasting plasma glucose levels in non
      diabetic individuals.
AB  - BACKGROUND/AIMS: Fasting plasma glucose (FPG) levels correlate with
      cardiovascular disease and mortality in both diabetic and non-diabetic subjects.
      G6PC2 encodes a pancreatic islet-specific glucose-6-phosphatase-related protein
      and G6pc2-null mice were reported to exhibit decreased blood glucose levels. Two
      recent genome-wide association studies have implicated a role for G6PC2 in
      regulation of FPGlevels in the general European population and reported the
      strongest association with the rs560887 SNP. The purpose of this study was to
      replicate this association in our independent epidemiological samples. METHODS:
      DNA samples from non-Hispanic white Americans (NHWs; n = 623), Hispanic Americans
      (n = 410) and black Africans (n = 787) were genotyped for rs560887 using TaqMan
      allelic discrimination. RESULTS: While no minor allele A of rs560887 was observed
      among blacks, its frequency was 33% in NHWs and 17.5% in Hispanics. The rs560887
      minor allele was associated with reduced FPG levels in non-diabetic NHWs (p =
      0.002 under an additive model). A similar trend of association was observed in
      non-diabetic Hispanics (p = 0.076 under a dominant model), which was more
      pronounced in normoglycemic subjects (p = 0.036). CONCLUSIONS: Our results
      independently confirm the robust association of G6PC2/rs560887 with FPG levels in
      non-diabetic NHWs. The observed evidence for association in Hispanics warrants
      further studies in larger samples.

PMID- 20029180
TI  - Preface to molluscan neurobiology: recent advances and new vistas.

PMID- 20029181
TI  - Developing nervous systems in molluscs: navigating the twists and turns of a
      complex life cycle.
AB  - Molluscs constitute a richly diversified phylum, containing abundant species that
      have successfully invaded a variety of habitats. Despite the long-standing
      importance of its various members as model species for neurobiology, research on
      the development of the molluscan nervous system has lagged behind that on several
      other phyla. Recent studies, however, have begun to sketch an overview of neural
      development during the complex life cycles of these animals, involving multiple
      larval and postlarval stages and often including processes of torsion and
      occasionally detorsion affecting the entire body plan. The first neurons appear
      early in life and innervate a variety of larval organs. The central and
      peripheral neurons that comprise the adult nervous system generally appear later
      in larval life. Metamorphosis involves the loss of many neurons and the gain of
      others, and yet more neurons change to accommodate transitions in modes of
      locomotion, feeding and habitat. But such large-scale transitions do not stop at
      metamorphosis as massive changes in body size and behavior occur during juvenile
      and adult stages, and the nervous system must change accordingly to meet the
      demands of expanding target tissues and the need to generate new behaviors. Work
      over the years has gradually revealed some of the genes important in molluscan
      neural development, but recent whole-genome, EST and microarray projects are now
      allowing much more rapid progress and providing a valuable molluscan perspective
      for understanding broader issues concerning the evolution of the nervous system
      across the animal kingdom.

PMID- 20029182
TI  - On the independent origins of complex brains and neurons.
AB  - Analysis of the origin and evolution of neurons is crucial for revealing
      principles of organization of neural circuits with unexpected implications for
      genomic sciences, biomedical applications and regenerative medicine. This article
      presents an overview of some controversial ideas about the origin and evolution
      of neurons and nervous systems, focusing on the independent origin of complex
      brains and possible independent origins of neurons. First, earlier hypotheses
      related to the origin of neurons are summarized. Second, the diversity of nervous
      systems and convergent evolution of complex brains in relation to current views
      about animal phylogeny is discussed. Third, the lineages of molluscs and basal
      metazoans are used as illustrated examples of multiple origins of complex brains
      and neurons. Finally, a hypothesis about the independent origin of complex
      brains, centralized nervous systems and neurons is outlined. Injury-associated
      mechanisms leading to secretion of signal peptides (and related molecules) can be
      considered as evolutionary predecessors of inter-neuronal signaling and the major
      factors in the appearance of neurons in the first place.

PMID- 20029183
TI  - Evolutionary conservation of the signaling proteins upstream of cyclic AMP
      dependent kinase and protein kinase C in gastropod mollusks.
AB  - The protein kinase C (PKC) and the cAMP-dependent kinase (protein kinase A; PKA)
      pathways are known to play important roles in behavioral plasticity and learning
      in the nervous systems of a wide variety of species across phyla. We briefly
      review the members of the PKC and PKA family and focus on the evolution of the
      immediate upstream activators of PKC and PKA i.e., phospholipase C (PLC) and
      adenylyl cyclase (AC), and their conservation in gastropod mollusks, taking
      advantage of the recent assembly of the Aplysiacalifornica and Lottia gigantea
      genomes. The diversity of PLC and AC family members present in mollusks suggests
      a multitude of possible mechanisms to activate PKA and PKC; we briefly discuss
      the relevance of these pathways to the known physiological activation of these
      kinases in Aplysia neurons during plasticity and learning. These multiple
      mechanisms of activation provide the gastropod nervous system with tremendous
      flexibility for implementing neuromodulatory responses to both neuronal activity
      and extracellular signals.

PMID- 20029186
TI  - The evolution of flexible behavioral repertoires in cephalopod molluscs.
AB  - Cephalopods are a large and ancient group of marine animals with complex brains.
      Forms extant today are equipped with brains, sensors, and effectors that allow
      them not to just exist beside modern vertebrates as predators and prey; they
      compete fiercely with marine vertebrates at every scale from small crustaceans to
      sperm whales. We review the evolution of this group's brains, learning ability
      and complex behavior. We outline evidence that although competition with
      vertebrates has left a deep impression on the brains and behavior of cephalopods,
      the original reorganization of their complex brains from their molluscan
      ancestors might have been forged in ancient seas millions of years before the
      advent of bony fishes.

PMID- 20029184
TI  - Molluscan memory of injury: evolutionary insights into chronic pain and
      neurological disorders.
AB  - Molluscan preparations have yielded seminal discoveries in neuroscience, but the
      experimental advantages of this group have not, until now, been complemented by
      adequate molecular or genomic information for comparisons to genetically defined
      model organisms in other phyla. The recent sequencing of the transcriptome and
      genome of Aplysia californica, however, will enable extensive comparative studies
      at the molecular level. Among other benefits, this will bring the power of
      individually identifiable and manipulable neurons to bear upon questions of
      cellular function for evolutionarily conserved genes associated with clinically
      important neural dysfunction. Because of the slower rate of gene evolution in
      this molluscan lineage, more homologs of genes associated with human disease are
      present in Aplysia than in leading model organisms from Arthropoda (Drosophila)
      or Nematoda (Caenorhabditis elegans). Research has hardly begun in molluscs on
      the cellular functions of gene products that in humans are associated with
      neurological diseases. On the other hand, much is known about molecular and
      cellular mechanisms of long-term neuronal plasticity. Persistent nociceptive
      sensitization of nociceptors in Aplysia displays many functional similarities to
      alterations in mammalian nociceptors associated with the clinical problem of
      chronic pain. Moreover, in Aplysia and mammals the same cell signaling pathways
      trigger persistent enhancement of excitability and synaptic transmission
      following noxious stimulation, and these highly conserved pathways are also used
      to induce memory traces in neural circuits of diverse species. This functional
      and molecular overlap in distantly related lineages and neuronal types supports
      the proposal that fundamental plasticity mechanisms important for memory, chronic
      pain, and other lasting alterations evolved from adaptive responses to peripheral
      injury in the earliest neurons. Molluscan preparations should become increasingly
      useful for comparative studies across phyla that can provide insight into
      cellular functions of clinically important genes.

PMID- 20029185
TI  - Comparative neurobiology of feeding in the opisthobranch sea slug, Aplysia, and
      the pulmonate snail, Helisoma: evolutionary considerations.
AB  - The motor systems that generate feeding-related behaviors of gastropod mollusks
      provide exceptional opportunities for increasing our understanding of neural
      homologies and the evolution of neural networks. This report examines the neural
      control of feeding in Helisoma trivolvis, a pulmonate snail that ingests food by
      rasping or scraping material from the substrate, and Aplysia californica, an
      opisthobranch sea slug that feeds by using a grasping or seizing motion. Two
      classes of neurons that are present in the buccal ganglia of both species are
      considered: (1) clusters of peptidergic mechanoafferent cells that transmit
      sensory information from the tongue-like radula/odontophore complex to the
      central motor circuit; and (2) sets of octopamine-immunoreactive interneurons
      that are intrinsic to the feeding network. We review evidence that suggests
      homology of these cell types and propose that their roles have been largely
      conserved in the control of food-scraping and food-grasping consummatory
      behaviors. We also consider significant differences in the feeding systems of
      Aplysia and Helisoma that are associated with the existence of radular closure in
      Aplysia, an action that does not occur in Helisoma. It is hypothesized that a
      major adaptation in the innervation patterns of analogous, possibly homologous
      muscles could distinguish the food-scraping versus food-grasping species. It
      appears that although core CPG elements have been largely conserved in this
      system, the neuromuscular elements that they regulate have been more
      evolutionarily labile.

PMID- 20029188
TI  - The modified Rankin Scale in acute stroke has good inter-rater-reliability but
      questionable validity.
AB  - BACKGROUND AND PURPOSE: The modified Rankin Scale (mRS), designed as a measure of
      disability in the community, has increasingly been administered in the acute
      stroke setting but has been poorly studied within the hospital environment. We
      prospectively studied the interrater reliability of the mRS in acutely
      hospitalised stroke patients and examined the effect of prior experience with the
      scale and use of a decision tool on the interrater agreement of trained raters.
      METHODS: Patients <4 days after stroke were recruited. Individuals from 3 trained
      rater groups (experienced, inexperienced and inexperienced with decision tool)
      independently scored each patient within 6 h of each other. Agreement was
      measured with the intraclass correlation (ICC) and the weighted kappa statistic
      (kappa(w)), with systematic bias evaluated using the bias index. RESULTS: Twelve
      raters scored 56 patients with overall agreement of ICC = 0.675. Agreement of
      kappa(w) = 0.686 was found between experienced and inexperienced raters but a
      modest systematic bias was present. Experience in rating patients appeared to
      play some role in affecting agreement but the decision tool did not improve the
      performance of inexperienced raters. CONCLUSIONS: Trained raters were found to
      have good interrater agreement overall when the mRS was scored in acute stroke
      patients but obvious problems with the interpretation and relevancy of the scale
      in this setting raise concerns about validity. The use of the mRS to rate
      disability in the acute hospital environment should be questioned.

PMID- 20029187
TI  - Proportion, risk factors and outcome of lacunar infarction: a hospital-based
      study in a Chinese population.
AB  - BACKGROUND: There is scant information on the proportion, risk factors and
      outcome of lacunar infarction in China. METHODS: Prospective registry data
      entered within 1 month after a first-ever stroke between March 2002 and March
      2007 were used from 4 Chinese hospitals. Data regarding stroke risk factors and
      baseline characteristics were examined in a long-term follow-up. Case fatality,
      death and dependency, and stroke recurrence were assessed at 30, 90, 180 days and
      1 year. Predictive factors for death at 1 year in patients with lacunar
      infarction were tested by logistic regression analysis. We constructed Kaplan
      Meier survival curves and compared groups with lacunar infarction and nonlacunar
      infarction by means of log rank tests for significant difference. RESULTS: A
      total of 3,905 patients with first-ever cerebral infarction were included, of
      whom 1,650 (42.3%) had a lacunar infarction and 2,255 (57.7%) a nonlacunar
      infarction. Case fatality was lower in patients with lacunar infarction at all 4
      time points (5.3, 6.4, 7.8 and 17.4%, respectively), as compared to patients with
      nonlacunar infarction (9.5, 14.3, 16.5 and 20.1%, respectively). Age, diabetes,
      smoking and NIHSS score at admission were the independent predictors for 1-year
      case fatality in patients with lacunar infarction. Death and dependency rates
      were also lower in patients with lacunar infarction than in those with nonlacunar
      infarction. Recurrent stroke was an important cause of death for lacunar
      infarction patients. CONCLUSIONS: The proportion of lacunar infarction in China
      is much higher than that in Western countries. The long-term prognosis of lacunar
      infarction is not benign.

PMID- 20029189
TI  - Nicergoline increases serum substance P levels in patients with an ischaemic
      stroke.
AB  - BACKGROUND: Aspiration pneumonia is one of the most important complications
      following ischaemic stroke, and a leading cause of mortality in stroke patients.
      This is particularly prevalent in patients with involvement of the basal ganglia,
      which may be due to impaired neurotransmission through lack of production of
      substance P. METHODS: Consecutive patients in the chronic stage, 1-3 months after
      cerebral ischaemic infarction, were assessed for basal ganglia involvement by
      magnetic resonance imaging. The patients were randomised to 4 weeks of treatment
      with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration
      of substance P was measured by radioimmunoassay. RESULTS: At entry to the study,
      mean concentration of substance P was significantly (p < 0.001) lower in patients
      with bilateral basal ganglia lesions than in patients with no or unilateral basal
      ganglia involvement. Nicergoline administration caused a significant (p = 0.021)
      increase from baseline in mean substance P concentration. No significant change
      was seen in the nicergoline-untreated patients (p = 0.626). Among the patients
      who received nicergoline, 11 patients had bilateral basal ganglia involvement and
      there was no significant mean change in substance P in these patients, whereas
      there was a significant increase (p = 0.032) in the 14 nicergoline-treated
      patients with no or unilateral basal ganglia involvement. CONCLUSIONS: The
      present study suggests a possible effect of nicergoline to increase substance P
      level in ischaemic stroke patients with partial damage to basal ganglia, who have
      a decreased swallowing response and consequent risk of aspiration pneumonia.
      Further trials of nicergoline treatment in patients at risk for aspiration
      pneumonia are warranted.

PMID- 20029190
TI  - Spatial distension variations are associated with focal atherosclerotic plaques.
AB  - BACKGROUND: Alterations in arterial absolute distension (AD) and relative
      distension (RD) in the common carotid artery (CCA), as observed by ultrasound,
      may relate to atherosclerotic processes in a nearby vascular segment. The main
      objective of the study was to establish to what extent these mechanical vascular
      alterations relate to carotid bulb stenosis. METHODS: The AD, RD and their
      interrecording variation (Delta AD and Delta RD), representing the spatial
      inhomogeneity of AD and RD, were evaluated in 308 CCA and associated with the
      degree of bulb stenosis. RESULTS: The mechanical CCA parameters were marginally
      correlated to the degree of ipsilateral (r = -0.14 for AD and r = -0.28 for RD)
      and contralateral stenosis (r = -0.21 for AD and r = -0.27 for RD). However,
      Delta AD (r = 0.54; p < 0.001) and Delta RD (r = 0.59; p < 0.001) were
      significantly correlated to ipsilateral stenosis, independent of age, gender and
      pulse pressure. CONCLUSIONS: The indices of CCA arterial stiffness are weakly
      associated with ipsilateral bulb stenosis, but their interrecording variation is
      a good indicator for atherosclerotic alterations in the carotid bulb. The results
      indicate that a focal atherosclerotic lesion is associated with modifications in
      the dynamic characteristics of a nearby vascular segment.

PMID- 20029191
TI  - JAK2 V617F mutation associated with cerebral venous thrombosis: a report of five
      cases.

PMID- 20029192
TI  - A simultaneous EEG and transcranial Doppler technique to investigate the
      neurovascular coupling in the human visual cortex.
AB  - Due to lacking energy stores, high energy consumption and dependency on a strict
      aerobic glycolysis, the brain is very dependent on an adequate blood supply of
      active neurons. Adequate regulation of the functionally induced local cerebral
      blood flow is assured by neurovascular coupling. Our understanding of its role in
      different disease processes has improved considerably in the last few years.
      Consequently, a diagnostic tool is needed which allows an easy and cost-effective
      investigation of the coupling in clinical conditions. A combined EEG and Doppler
      technique might be suitable in this regard. This review gives a short overview of
      the neurophysiological background and the techniques, before validation studies
      and first clinical applications are addressed.

PMID- 20029193
TI  - The spot sign in intracerebral hemorrhage: the importance of looking for contrast
      extravasation.
AB  - BACKGROUND: The 'spot sign' is a bright spot on computerized tomography
      angiography (CTA) source images predictive of hematoma growth. Contrast
      extravasation (CE) is seen on routine head CT following CTA as pooling of
      contrast within the hematoma. Our aim was to re-evaluate the predictive value of
      both the spot sign and CE and measure the reliability of scoring them. METHODS:
      Consecutive cases of spontaneous intracerebral hemorrhage (ICH) presenting within
      4 h. The presence of a 'spot' and CE, ICH and intraventricular hemorrhage volume
      at baseline and on follow-up scans were assessed. Clinical outcome was captured
      using the modified Rankin Scale on hospital discharge. RESULTS: We identified 28
      patients with a mean age of 56.8 years, median ICH volume of 19 ml, and median
      NIH Stroke Scale score on admission of 17.5. 11/27 (40.7%) had a positive spot
      and 13/22 (59.1%) had CE. Interrater reliability was 0.812 (95% CI 0.57-0.91, p <
      0.001) for the spot sign and 0.952 (95% CI 0.89-0.98, p < 0.001) for CE. ICH
      volume increased in 16/28 (57.1%) patients. Both the spot sign and CE were
      associated with ICH growth (p < 0.001) and poor outcome (p < 0.001). CONCLUSIONS:
      In ICH patients, the presence of the spot sign or CE is highly correlated with
      early ICH growth. In our experience, CE is a more sensitive predictor of ICH
      growth with a better negative predictive value than the spot sign; CE is more
      consistently identified even by experienced clinicians. Postcontrast CT should be
      done routinely after CTA in patients presenting with ICH within 4 h. Patients who
      are CE-positive may be candidates for hemostatic therapies or early surgical
      intervention.

PMID- 20029194
TI  - Symptom progression or fluctuation in transient ischemic attack patients predicts
      subsequent stroke.
AB  - BACKGROUND: The aim of this study was to investigate whether progression or
      fluctuation of transient ischemic attack (TIA) symptoms is a predictor of
      subsequent stroke. METHODS: We prospectively analyzed 113 consecutive patients
      admitted with a diagnosis of classical TIA with symptom duration of less than 24
      h. We assessed the background characteristics, TIA symptoms, attack
      characteristics, results of in-hospital examinations, and prescription of
      antithrombotic agents on discharge for each patient. We then analyzed the factors
      related to progression or fluctuation of TIA symptoms. RESULTS: Of the 113
      patients, 35 (31.0%) exhibited symptom progression or fluctuation. Subsequent
      stroke occurred in 12 (10.6%) patients within 180 days. Symptom progression or
      fluctuation was significantly related to the TIA symptoms of speech disturbance,
      hemiparesis, and monoparesis, and were also related to subsequent stroke
      occurrence within 90 days (29 vs. 3%, p = 0.004) and 180 days (23 vs. 5%, p =
      0.008). In a logistic regression model analysis, symptom progression or
      fluctuation was a significant predictor of subsequent stroke within 90 days (odds
      ratio = 7.65, 95% CI 1.27-46.06) and 180 days (odds ratio = 4.44, 95% CI 1.08
      18.13), independently of other predictors demonstrated in previous studies.
      CONCLUSIONS: Progression or fluctuation of TIA symptoms may be an important
      predictor of subsequent stroke. A detailed interview about the characteristics of
      each attack is also indispensable for the provision of appropriate care to TIA
      patients.

PMID- 20029195
TI  - Dynamic cerebral autoregulation is compromised acutely following mild ischaemic
      stroke but not transient ischaemic attack.
AB  - BACKGROUND: Dynamic cerebral autoregulation (dCA), the process by which the
      cerebral blood flow (CBF) is normally maintained relatively constant despite
      fluctuations in beat-to-beat blood pressure (BP), is impaired acutely following
      major ischaemic stroke. It is uncertain if dCA is impaired acutely after mild
      ischaemic stroke or transient ischaemic attack (TIA). We assessed dCA in patients
      acutely and sub-acutely following TIA or mild ischaemic stroke. METHODS: Nineteen
      consecutive mild ischaemic stroke patients and 17 consecutive TIA patients
      underwent recordings of beat-to-beat BP, cerebral blood flow velocity (bilateral
      transcranial Doppler insonation of the middle cerebral artery) and heart rate a
      median of 36 h from onset and again a median of 96 h from onset. Dynamic
      autoregulatory indices (ARI) were then calculated from these data and the results
      compared to 22 age-, BP- and gender-matched controls. RESULTS: ARI was
      significantly reduced in affected hemispheres of mild stroke patients at baseline
      compared to controls (4.0 +/- 1.7 vs. 5.6 +/- 1.1, p < 0.01) and remained so
      after adjustment for significant covariates. ARI was significantly reduced in
      both affected (4.0 +/- 2.7 vs. 5.6 +/- 1.1, p = 0.03) and unaffected hemispheres
      (4.2 +/- 1.8 vs. 5.6 +/- 1.1, p = 0.01) of mild stroke patients at follow-up
      compared to controls. However, after adjustment for significant covariates
      including ipsilateral carotid stenosis these results were not significant. No
      reduction in ARI was seen in TIA patients. CONCLUSIONS: The impairment of
      cerebrovascular haemodynamic control that was observed acutely following mild
      ischaemic stroke may have implications for the appropriate timing of anti
      hypertensive therapy acutely following mild ischaemic stroke. No impairment of
      cerebrovascular haemodynamic control was seen following TIA.

PMID- 20029196
TI  - Long-term outcomes of ischemic stroke patients with concurrent intracranial and
      extracranial stenoses and ischemic heart disease.
AB  - BACKGROUND AND PURPOSE: Coexisting ischemic heart disease (IHD) and concurrent
      atherosclerosis of intracranial and extracranial vessels is common in Asians.
      This study aims to investigate the long-term outcomes of ischemic stroke patients
      with concurrent stenoses and IHD. METHODS: This was a prospective cohort study in
      Hong Kong. Consecutive Chinese patients with acute ischemic stroke underwent MRI,
      magnetic resonance angiography and carotid duplex sonography. RESULTS: A total of
      428 patients were included. The mean follow-up period was 65 months (up to 87
      months). Ninety-three patients (22%) died of any cause and 104 patients (22%)
      suffered from nonfatal vascular events. Fifty-four patients (13%) had IHD. Among
      them, 27 patients (50%) had concurrent stenoses. In patients with concurrent
      stenoses and IHD, only 3 (11%) were free of death and recurrent vascular events.
      Eight (30%) had recurrent nonfatal stroke, 7 (26%) had nonfatal myocardial
      infarct (MI) and 11 (41%) died, 6 (22%) of them due to fatal MI. The overall 5
      year cumulative rates of mortality, recurrent vascular events and combined poor
      outcomes were 21, 23 and 43%, respectively. In patients with concurrent stenoses
      and IHD, these rates were 40, 50 and 83%, respectively. More deaths (log rank:
      6.56; p = 0.01), recurrent vascular events (log rank: 25.24; p < 0.001) and poor
      outcomes (log rank: 27.50; p < 0.001) were found among patients with concurrent
      stenoses and IHD. CONCLUSIONS: Ischemic stroke patients with concurrent stenoses
      and IHD had high risks of death and recurrent vascular events. Future studies on
      aggressive medical therapy and early cardiac interventions in this high-risk
      group of stroke patients are warranted.

PMID- 20029198
TI  - High prevalence of peripheral arterial disease in patients with acute ischaemic
      stroke.
AB  - BACKGROUND: After acute ischaemic stroke (AIS) or transient ischaemic attack
      (TIA), the detection of peripheral arterial disease (PAD) as a marker of
      generalized atherosclerosis may improve the risk stratification and prevention of
      future atherothrombotic events. We aimed to determine the prevalence of PAD
      indicated by an ankle-brachial index (ABI) of < or =0.9 in a large cohort of
      patients with AIS/TIA. METHODS: In this prospective, multicentre, Austrian, cross
      sectional study (OECROSS), 759 patients with AIS or TIA were recruited for a
      systematic assessment of cardiovascular risk profiles and Doppler ultrasound at
      the ankle and brachial artery to calculate the ABI from systolic blood pressure
      readings. RESULTS: 739 patients (97.4%) had a complete ABI assessment. The mean
      age was 69.5 (+/- 12.1) years, and 55.8% of the patients were men. 81.6% of the
      patients had AIS and 18.4% had TIA. Only 6.2% of the patients had a history of
      PAD, but an abnormal ABI of < or =0.9 was found in 44.9%. Patients with an ABI of
      < or =0.9 were more likely (p < 0.05) to be older and have a history of PAD,
      hypertension, diabetes and congestive heart failure. An ABI of < or =0.9 was
      significantly associated (p < 0.0005) with a presence of carotid stenosis of >50%
      and an Essen Stroke Risk Score of >2, indicating a risk of > or =4% per year of
      stroke recurrence. DISCUSSION: A high proportion of patients with AIS/TIA have
      subclinical PAD, a cross-risk stroke physicians should be aware of. Large
      longitudinal studies are needed to elucidate whether the ABI can improve our
      estimation of the risk of future atherothrombotic events and help in optimizing
      secondary prevention.

PMID- 20029197
TI  - The -928 G/C and -362 G/C single-nucleotide polymorphisms in the promoter of MCP
      1: Increased transcriptional activity and novel binding sites.
AB  - BACKGROUND: The -928 guanine (G)/cytosine (C) and -362 G/C single-nucleotide
      polymorphisms (SNPs) in the proximal promoter region of the monocyte
      chemoattractant protein 1 gene have been associated with an increased risk for
      intimal medial thickness and carotid atherosclerosis, respectively. We
      characterized the transcriptional activity of these two SNPs in vitro and
      identified transcription factors that bind to them. METHODS: The proximal
      promoter region spanning bases -2746 to +440 was sequenced in subjects with
      carotid atherosclerosis. Two SNPs consisting of C-for-G substitution at bases 
      928 and -362 were characterized. Each observed haplotype was inserted into a
      luciferase reporter and transfected into mammalian cells. RESULTS: Stimulation
      with 12-O-tetradecanoylphorbol 13-acetate increased transcriptional activity of
      the -928 C plasmid (p = 0.005). The basal transcription activities of the
      plasmids containing -928 C and -362 C were also increased (p < 0.001 and p <
      0.0001, respectively). Electrophoretic mobility shift assay (EMSA) and DNA
      footprinting identified an Ah receptor nuclear translocator protein (ARNT)
      binding site at the -928 C SNP. EMSA data indicated signal transducers and
      activators of transcription (STAT) binding at the -362 G SNP. A nuclear binding
      protein, poly(ADP-ribose) polymerase (PARP) 1, was purified from the -928 C SNP
      site and identified by mass spectroscopy. CONCLUSION: The -928 C SNP and the -362
      C SNP are associated with increased transcriptional activity in vitro, but the 
      362 G site is not. The -928 C SNP is associated with PARP-1 and ARNT binding, and
      the -362 G is associated with a STAT binding site.

PMID- 20029199
TI  - Predictors of one-year disability and death in Chinese hospitalized women after
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Women have a worse functional outcome after stroke, but
      the specific factors associated with a poor outcome in women are rarely reported.
      This study was designed to investigate the clinical predictors of 1-year
      disability and death in women after ischemic stroke. METHODS: Patients with
      ischemic stroke consecutively registered from March 2002 to July 2007 were
      followed prospectively for 1 year. Multivariate regression models were employed
      to analyze predictors of disability (defined as modified Rankin scale score, mRS,
      3-5) and death. RESULTS: A total of 2,774 ischemic stroke patients were included
      with 1,119 (40.3%) females (mean age 65 +/- 13.5 years). Among female patients,
      disability (mRS 3-5) is 1.68-fold higher and case fatality is 1.23-fold higher
      than in men at the 1-year follow-up. Diabetes is an independent predictor of 1
      year disability among women (odds ratio, 1.56; 95% confidence interval, CI, 1.01
      2.39). In-hospital acute renal failure (hazard ratio, HR, 7.26; 95% CI, 3.47
      5.19), suboptimal antiplatelets (HR, 0.55; 95% CI, 0.37-0.83) and
      antihypertensive therapy (HR, 0.61; 95% CI, 0.42-0.90) are associated with death
      at 1 year after stroke among women. CONCLUSIONS: The present study indicates that
      diabetes, in-hospital acute renal failure, suboptimal antiplatelets and
      antihypertensive therapy are the possible explanations for the poor 1-year
      outcome of women hospitalized with ischemic stroke.

PMID- 20029200
TI  - MicroRNAs miR-1, miR-133a, miR-133b and miR-208 are dysregulated in human
      myocardial infarction.
AB  - OBJECTIVES: MicroRNAs (miRNAs) are noncoding single-stranded RNA molecules that
      regulate gene expression in physiological functions, development and disease. In
      recent studies, three miRNAs have been described as muscle or cardiac specific:
      miR-1, miR-133, and miR-208, being involved in heart development and disease; but
      there are limited data on their role in human myocardial infarction (MI). We
      therefore analyzed their expression in human MI. METHODS: Autopsy samples of
      infarcted heart tissue from 50 patients with MI, 8 healthy trauma victims and 9
      fetuses that died in utero were included. miRNAs miR-1, miR-133a/b and miR-208
      were analyzed using quantitative real-time polymerase chain reaction. RESULTS:
      miR-208 was upregulated, whereas miR-1 and miR-133a were downregulated in MI
      compared to healthy adult and fetal hearts. All four tested miRNAs were
      downregulated in fetal hearts compared to healthy adult hearts. CONCLUSIONS: Our
      study showed the involvement of muscle- and/or cardiac-specific miRNAs miR-1, miR
      133a/b and miR-208 in human MI. The most significant finding was upregulation of
      miR-208 and downregulation of miR-1 and miR-133a in MI compared to healthy adult
      hearts. Some patterns of miRNA expression were similar in MI and fetal hearts,
      supporting the concept of cardiac gene reprogramming in the remodeling of the
      heart.

PMID- 20029202
TI  - Robot-assisted laparoscope fundoplication for gastroesophageal reflux disease: a
      systematic review of randomized controlled trials.
AB  - OBJECTIVE: To evaluate the efficacy and safety of robot-assisted fundoplication
      (RAF) for treating gastroesophageal reflux disease (GERD). METHODS: Randomized
      controlled trials (RCTs) or quasi-RCTs were searched for in PubMed, EMBASE, the
      Cochrane Library, SCI, Chinese Biomedical Database, China Academic Journals Full
      Text Database, Chinese Scientific Journals Database, China online journals, and
      related journals. We evaluated the quality of the included studies by using the
      5.0.1 Cochrane Handbook standards and analyzed the data using the Cochrane
      Collaboration's RevMan 5.0. RESULTS: Five studies (n = 181) were included. A meta
      analysis showed that besides the time taken to carry out fundoplication (p <
      0.00001), both RAF and conventional laparoscopic fundoplication (CLF) were
      similar in postoperative antisecretory medication (p = 1.0), intraoperative
      conversion to open surgery (p = 0.94), postoperative dysphagia (p = 1.0),
      pneumothorax (p = 1.0), total intraoperative complications (p = 0.24), the time
      of hiatal dissection (p = 0.98), the time of incision to completion of sutures (p
      = 0.95), total operation time (p = 0.16), hospital stay (p = 0.97), and total
      cost (p = 0.25). CONCLUSIONS: The current evidence demonstrates that RAF is safe
      and effective in treating GERD. The weakness of this treatment method is that it
      prolongs the time necessary to carry out fundoplication. However, RAF should be
      the future trend for treating GERD.

PMID- 20029203
TI  - Current standings of the proton pump inhibitor and clopidogrel co-therapy: review
      on an evolving field with the eyes of the gastroenterologist.
AB  - The negative effect of proton pump inhibitors (PPI) on the antiplatelet function
      of clopidogrel has only recently emerged on the horizon of cardiological
      interest. To date, one can only find 10 peer-reviewed papers on PubMed on this
      issue, although the increasing activity is unquestionable. Besides publications,
      conference reports and official web sites are therefore important sources of
      information. In this field, the first step was made by an experimental study
      proving the adverse effect of omeprazole on clopidogrel function. Consequently,
      retrospective studies reported a significant increase of major adverse
      cardiovascular events among patients taking the combination of omeprazole and
      clopidogrel. Based on the paucity of quality data and limitations of studies
      conducted on this interaction, some are still reluctant to confirm the pathogenic
      role of PPI and clopidogrel interaction in the development of reinfarctions. One
      step further ahead, admitting the risks related to the combination of these two
      drugs, the next question to be decided is whether we face a class effect, or
      thanks to the different metabolic pathways there are indeed relevant differences
      among PPIs. There is a lot at stake, since the volume of patients taking the dual
      aspirin-clopidogrel antiplatelet therapy and thereby needing gastroprotection is
      immense, rendering a huge responsibility to the societies and committees who are
      making proposals on the selection of appropriate PPIs.

PMID- 20029204
TI  - Atherosclerosis and colorectal carcinogenesis: shared risk factors or common
      pathogenesis?

PMID- 20029205
TI  - Cardiovascular risk status can influence the colorectal cancer screening
      strategy.

PMID- 20029206
TI  - A systematic review on intrapyloric botulinum toxin injection for gastroparesis.
AB  - BACKGROUND: Though trials evaluating the effect of intrapyloric botulinum toxin
      injection on gastroparesis have been reported, there is no agreement whether
      botulinum toxin can effectively relieve the symptoms and improve the results of
      gastric emptying study in patients with gastroparesis. We performed a systematic
      literature review to address this issue. METHODS: Databases including PubMed,
      EMBASE, and the Cochrane Library and Science Citation Index were searched. Two
      reviewers independently identified relevant trials. Outcome measures were the
      improvement of subjective symptoms and objective measurement. RESULTS: 15 reports
      were included; only 2 randomized controlled trials were available. Almost all the
      non-randomized trials reported significant improvement in subjective symptoms and
      objective gastric emptying study after botulinum toxin injection. While the 2
      randomized controlled trials did not confirm the efficacy of botulinum toxin
      injection, none of the individual trials showed that there was statistically
      significant subjective and objective improvement in the active patients when
      compared with patients receiving placebo. CONCLUSIONS: Available high-quality
      trials showed that intrapyloric botulinum toxin injection could not significantly
      relieve subjective symptoms and improve objective measurement in patients with
      gastroparesis, and there is no evidence to recommend botulinum toxin injection
      for the treatment of gastroparesis.

PMID- 20029207
TI  - Undifferentiated histology after endoscopic resection may predict synchronous and
      metachronous occurrence of early gastric cancer.
AB  - BACKGROUND: Endoscopic resection (endoscopic mucosal resection, EMR, and
      endoscopic submucosal dissection, ESD) has been accepted worldwide as a less
      invasive standard treatment for early gastric cancer (EGC). However, the risk of
      synchronous and metachronous gastric cancer developing in the post-endoscopic
      resection patient has become a major problem. We investigated the incidence and
      characteristics of synchronous and metachronous multiple gastric cancers in a
      retrospective study of patients with EGC after endoscopic resection. PATIENTS AND
      METHODS: We studied the clinicopathological features of 235 patients with EGC who
      had undergone endoscopic resection and were periodically followed up using
      endoscopic examinations (181 with a single lesion, 34 synchronous multiple
      lesions, and 20 metachronous multiple lesions). RESULTS: The overall incidence of
      synchronous and metachronous multiple gastric cancer was 14.5 and 8.5%,
      respectively, during a follow-up of 12-77 (median 26.5) months. Undifferentiated
      histology of the primary lesion was related to the occurrence of synchronous
      gastric cancer (p < 0.001). Undifferentiated histology and upper location of the
      primary lesion were correlated with the occurrence of metachronous gastric cancer
      (p = 0.002, 0.001). Most synchronous and metachronous lesions were well to
      moderately differentiated (82.4 and 80.0%); however, the proportion with
      undifferentiated histology (including poorly differentiated carcinoma and signet
      ring cell carcinoma) in synchronous and metachronous gastric cancer was
      significantly higher than in single gastric cancer (p = 0.008). CONCLUSIONS:
      Undifferentiated histology of EGC may predict the occurrence of synchronous and
      metachronous lesions after endoscopic resection.

PMID- 20029208
TI  - Pharmacological dependency in chronic treatment of gastroesophageal reflux
      disease: a randomized controlled clinical trial.
AB  - BACKGROUND: Despite evidence of the overuse of acid suppressive medication for
      gastroesophageal reflux disease (GERD), a transfer to noncontinuous therapy after
      long-term treatment proves difficult. AIM: To quantify the effect of blinded
      dosage reduction after long-term therapy on symptom control and quality of life
      while assessing pharmacological and placebo needs. METHODS: Primary care patients
      with a history of GERD and long-term treatment were randomized to daily placebo
      with pantoprazole rescue (n = 141) or daily pantoprazole with placebo rescue (n =
      62) upon relief after 4 weeks pantoprazole 20 mg. The number of rescue tablets,
      symptom control and generic quality of life were analyzed. RESULTS: Measured from
      the daily placebo arm, 19% of the patients terminated treatment, 33% managed with
      2-6 tablets/week, 38% needed a daily dosage and 10% needed more than a daily
      dosage in the long run. At these final dosages, symptom control and quality of
      life were dosage-independent and, furthermore, equal to values of patients on
      fixed daily pantoprazole. A temporal decrease in well-being was seen in 24% of
      the patients. CONCLUSION: A significant placebo response is apparent in long-term
      users of acid suppressive medication and pharmacological dependency is
      overestimated. Despite their history of long-term treatment, the majority of GERD
      patients can be switched from daily to on-demand treatment without impairing
      symptom control and quality of life.

PMID- 20029209
TI  - Natural history of functional dyspepsia: a 10-year population-based study.
AB  - BACKGROUND: Functional dyspepsia (FD) is a common disorder, but information on
      its natural history is limited. AIM: To study the natural history of FD as
      assessed by 2 criteria over a 10-year period. METHOD: A population-based study
      conducted by mailing a questionnaire to the same age- and gender-stratified
      random sample of the Icelandic population aged 18-75 in 1996 and again in 2006.
      FD was estimated by the Functional Dyspepsia Score List and by dyspepsia
      subgroups categorized into 4 groups: (1) frequent upper pain, (2) meal-related,
      (3) nausea or vomiting, and (4) combinations of these groups. RESULTS: FD was
      diagnosed in 13.9% of the subjects in the 1996 sample (11.3% male, 15.8% female)
      and 16.7% in 2006 (12.3% male, 20.2% female) with a significant difference
      between males and females in 2006. Dyspepsia subgroup criteria showed a higher
      prevalence than conventional FD criteria. The proportion of FD subjects in one of
      the dyspepsia subgroups was low. There was a significant relationship between FD
      and heartburn and irritable bowel syndrome. A high proportion of subjects who
      seek medical care have FD. CONCLUSION: FD was stable over the 10-year period, but
      there was turnover in symptoms and increased intensity and frequency of
      gastrointestinal pain. Dyspepsia subgroup criteria showed a higher prevalence
      than FD, which was more common in young subjects and females. FD poses a heavy
      burden on the health care system.

PMID- 20029210
TI  - Caspase-4 activation in association with decreased adenosine deaminase activity
      may be a factor for gastric ulcer.
AB  - BACKGROUND/AIMS: Adenosine deaminase (ADA)-deficient disease, a severe combined
      immunodeficiency, is most commonly associated with gastrointestinal disorders
      such as ulcer. The present study investigated the role of ADA in the pathogenesis
      of gastric ulcer. METHODS: ADA activity was measured in a variety of organs and
      tissues from rats and in human gastric biopsy samples from patients who underwent
      gastrofiberscope. An MTT assay and TUNEL staining were carried out, and activity
      of caspase-3 and -4 was enzymatically measured in MKN45 human gastric cancer
      cells. In the Western blot analysis, caspase-4 activation was identified in
      gastric biopsy samples. RESULTS: In rat organs and tissues, the epithelium of the
      gastrointestine exhibited higher ADA activity. The ADA inhibitor EHNA reduced
      cell viability, increased TUNEL-positive cells, and activated caspase-3 and -4 in
      MKN45 cells. For gastric biopsy samples, much lower ADA activity was found in
      gastric ulcer tissues, with a tendency of caspase-4 activation. CONCLUSION: A
      decline in ADA activity and the ensuing increase in intracellular adenosine
      concentrations for the stomach could induce gastric epithelial cell apoptosis by
      activating caspase-4 and the effector caspase-3. This may represent a fresh
      pathogenetical pathway for gastric ulcer relevant to ADA activity and caspase-4
      activation.

PMID- 20029211
TI  - Prevalence and factors related to substance use among adolescents with eating
      disorders.
AB  - OBJECTIVE: Very few studies have assessed substance use in clinical samples of
      adolescents with eating disorders (ED). This paper reports the prevalence of
      regular or risky substance use (RRSU) and substance use disorder (SUD) in
      adolescents with ED. METHODS: The Teen-Addiction Severity Index (T-ASI), the
      Youth Self-Report (YSR) scale and substance use questionnaires were administered
      to 95 adolescent patients aged 12-17 years who fulfilled the DSM-IV-TR diagnostic
      criteria for anorexia nervosa, bulimia nervosa and ED not otherwise specified.
      All patients were consecutively attended at an Eating Disorders Unit. RESULTS:
      14.7% presented SUD related to tobacco, 3.2% to cannabis, 1.1% to alcohol, and
      1.1% to other substances. Patients with RRSU-SUD of any substance except tobacco
      were 34.7%. Patients with RRSU-SUD failed more subjects, repeated more school
      years and had higher scores on T-ASI scales of problems at school, family
      function and social relationships, and on YSR scales of delinquent behavior and
      externalizing problems. CONCLUSIONS: Substance use problems in ED adolescents are
      frequent and formal screening of them as well as a specific therapeutic approach
      are necessary.

PMID- 20029212
TI  - Cost-effectiveness of home visits in the outpatient treatment of patients with
      alcohol dependence.
AB  - The purpose of this study was to compare the cost-effectiveness of conventional
      outpatient treatment for alcoholic patients (CT) with this same conventional
      treatment plus home visits (HV), a new proposal for intervention within the
      Brazilian outpatient treatment system. A cost-effectiveness evaluation alongside
      a 12-week randomized clinical trial was performed. We identified the resources
      utilized by each intervention, as well as the cost according to National Health
      System (SUS), Brazilian Medical Association (AMB) tables of fees, and others
      based on 2005 data. The incremental cost-effectiveness ratio (ICER) was estimated
      as the main outcome measure - abstinent cases at the end of treatment. There were
      51.8% abstinent cases for HV and 43.1% for CT, a clinically relevant finding.
      Other outcome measures, such as quality of life, also showed significant
      improvements that favored HV. The baseline scenario presented an ICER of USD
      1,852. Sensitivity analysis showed an ICER of USD 689 (scenario favoring HV) and
      USD 2,334 (scenario favoring CT). The HV treatment was found to be cost-effective
      according to the WHO Commission on Macroeconomics and Health.

PMID- 20029213
TI  - Timing of birth and risk of multiple sclerosis in the Scottish population.
AB  - Development of multiple sclerosis (MS) is believed to result from interplay of
      genes and environmental factors, which may be anticipated to act in a seasonal
      manner. Scotland has the highest prevalence of MS in the world. We aimed to
      determine if risk of multiple sclerosis is associated with season of birth in the
      Scottish population. Data for MS patients within the West of Scotland (n = 1,309)
      was obtained. Birth rates of MS patients were compared with national (n =
      6,198,352) and regional (n = 664,447) controls. Excess MS births occur in the
      spring months, with 22% more than expected (401 observed vs. 328 expected, p <
      0.0001). Peak month in both sexes was April. Fewer MS births occurred in autumn,
      with 16% fewer births compared with regional controls (275 observed vs. 328
      expected, p = 0.01). Our study, the largest in the Scottish population,
      demonstrates season of birth and risk of MS are associated. Elucidating potential
      environmental factor(s) accounting for such an association remains a challenge.

PMID- 20029214
TI  - Month of birth and multiple sclerosis risk in Scotland.

PMID- 20029215
TI  - Carpal tunnel syndrome: associations between risk factors and laterality.
AB  - AIMS: The investigation of the association between known risk factors and
      laterality in patients with carpal tunnel syndrome (CTS). PATIENTS AND METHODS:
      130 consecutive subjects with CTS only, or mainly, in the left hand were compared
      with 130 consecutive subjects with CTS only, or mainly, in the right hand. The
      following parameters were recorded: age, sex, job, handedness, hand mainly used
      in daily activities, BMI, diabetes mellitus, thyroid dysfunction, wrist trauma
      and connective tissue diseases. RESULTS: A left dominant hand was independently
      associated with 13-fold higher odds for left-hand CTS, while a right dominant
      hand had 5-fold higher odds for right-hand CTS. Right-hand CTS was more frequent
      in younger subjects and females. CONCLUSION: Older age, higher BMI and diabetes
      mellitus were more prevalent in patients with bilateral CTS. Age and BMI were
      independently associated with bilateral CTS.

PMID- 20029216
TI  - Neuropsychiatric profiles of patients with insulinomas.
AB  - BACKGROUND/AIMS: Insulinoma is a rare and potentially curable disease. It is
      often misdiagnosed as neurological or psychiatric disorder. This study was
      performed to characterize the neuropsychiatric symptoms (PNS) of the patients
      with insulinoma from a regional clinical center. METHODS: All medical records of
      the patients with histopathologically identified insulinoma were reviewed during
      the period from 1998 to 2008. A case-control analysis was performed to compare
      the demographic data, details of clinical presentation, biochemical findings,
      tumor localization, and intraoperative findings between the patients with and
      without a prior misdiagnosis. RESULTS: Among 42 patients with insulinoma, 25
      patients with PNS were initially misdiagnosed as having a neurological or
      psychiatric disease, while 17 patients with no PNS were correctly diagnosed. Most
      (64%) of PNS cases were not diagnosed correctly until 12 months after the first
      consultation. In patients with PNS that remained undiagnosed for at least 5
      years, the most frequent symptoms were confusion, convulsion, and visual
      disturbances. Twelve cases of PNS were initially misdiagnosed as epilepsy and 3
      of them showed epileptiform discharges on electroencephalography. CONCLUSIONS:
      Episodic hypoglycemia induced by insulinoma can greatly mimic neurological and
      psychiatric presentation. A thorough history taking and inpatient assessment are
      necessary in evaluating recurrent neurological and psychiatric symptoms.

PMID- 20029217
TI  - Relationship between cerebral hypoxic tissue volume and prognosis after stroke.
AB  - BACKGROUND/AIMS: Between 50 and 70% of stroke survivors suffer from severe
      disabilities such as paralysis and aphasia. Poor stroke outcome is a reflection
      of our incomplete understanding of the underlying mechanisms, and hence the
      capacity to implement appropriate treatment(s). We evaluated hypoxic tissue after
      stroke and patient condition severity and prognosis. METHODS: Hypoxic tissue
      volume was quantified within 14 days after stroke. Patients were classified as
      hypoxic positive or negative. Patients were evaluated at imaging and 21 days
      later. Prognosis was assessed at 30 and 90 days. RESULTS: Significant improvement
      was shown in hypoxia-positive (vs. hypoxia-negative) patients (p < 0.05). There
      were significant positive relationships between the volume of hypoxic tissue and
      the improvement in specialized test scores at 90 days (p < 0.05 for both).
      Presence of hypoxic tissue within 14 days after cerebral stroke was related to
      recovery at 3 weeks and prognosis at 90 days. CONCLUSIONS: The assessment of
      hypoxic tissue volume after stroke may be useful in predicting patient recovery.

PMID- 20029218
TI  - Borderlands of transient ischemic attacks, seizures and other transient
      neurological deficits. Commentary on de Reuck and van Maele: transient ischemic
      attacks and inhibitory seizures in elderly patients (Eur Neurol 2009;62:344-348).

PMID- 20029219
TI  - Distal migration of thrombus during intra-arterial thrombolysis.

PMID- 20029220
TI  - Amniotic fluid index in low-risk, post-dates pregnancies.
AB  - OBJECTIVE: To determine normal values for amniotic fluid index (AFI) in
      uncomplicated post-dates singleton pregnancies and compare it to current
      reference ranges. POPULATION: Four hundred and forty-eight women with singleton,
      uncomplicated pregnancies, presenting for post-dates assessment (gestation 40+0
      to 42+0 weeks) between January 1, 2004 and June 30, 2005. METHODS: Ultrasound
      assessment of liquor to calculate the AFI. RESULTS: The mean and standard
      deviation for AFI in the sample was 9.86 (SD 3.4), which is significantly
      different to the mean of the currently used reference range (mean 11.6, SD 3.9, p
      < 0.0001). The 5th percentile in this population was 4.6 cm. CONCLUSIONS: This
      study has demonstrated lower mean and 5th percentile values for AFI in post-dates
      pregnancies than current reference ranges. It has the largest published UK study
      population, and can therefore be used as a reference range in similar
      populations, which is likely to reduce unnecessary obstetric interventions.

PMID- 20029221
TI  - Potential errors with rapid analysis techniques: partial duplication 21q
      resulting from a paternal paracentric insertion uncovered in chorionic villus
      sampling by fluorescence in situ hybridization.
AB  - We report on partial duplication 21q resulting from a paternal insertion
      identified during prenatal diagnosis. While performing interphase fluorescence in
      situ hybridization (I-FISH), we were able to identify 3 signals of the LSI 21
      Spectrum Orange probe with chorionic villus sampling. Using standard cytogenetic
      analysis, I-FISH and GTG banding, structural aberrations in 21q in the parents
      and in the fetus could not be reliably determined. Applying metaphase
      fluorescence in situ hybridization (M-FISH), we identified a recombinant
      chromosome 21 carrying an interstitial duplication of the Down syndrome critical
      region inherited from the father. Both data from our analysis and published
      literature recommend the use of rapid testing methods such as I-FISH and standard
      cytogenetic analysis in prenatal diagnosis. It became obvious that I-FISH would
      not detect such a particular aberration. Thus, karyotyping, I-FISH and M-FISH
      should be performed in all Down syndrome cases.

PMID- 20029222
TI  - Is antibiotic prophylaxis necessary in elective laparoscopic surgery for benign
      gynecologic conditions?
AB  - BACKGROUND: The use of prophylactic antibiotics in gynecologic laparoscopic
      surgery is still popular and many gynecologic surgeons believe that prophylactic
      antibiotic therapy will decrease the incidence of postoperative infection
      complications. AIM: The aim of this prospective cohort study was to investigate
      the opportunity of prophylactic antibiotics to prevent early postoperative
      infections and febrile morbidity in elective laparoscopic surgery for benign
      gynecological conditions. METHODS: 300 women who underwent laparoscopic surgery
      for benign gynecological conditions were included in the study. After the
      patients were included they were divided in two groups (ratio 1:1). Group A (n =
      150) received 2 g of cefazolin (Cefamezin; Pfizer Italia Srl, Italy) 30 min
      before surgery and group B (n = 150) received no antibiotic prophylaxis. RESULTS:
      No postoperative infection was diagnosed for a total of 300 study patients. The
      overall rate of febrile morbidity was 3.3% for a total of 300 patients (1.3% for
      group A and 2% for group B). No differences in infection complications and
      febrile morbidity were found between the two groups. CONCLUSION: Postoperative
      infection complications in laparoscopic gynecologic surgery without antimicrobial
      prophylaxis are negligible and overlapping to those obtained with cefazolin
      prophylaxis.

PMID- 20029223
TI  - In-office thermachoice III ablation: a comparison of two anesthetic techniques.
AB  - BACKGROUND: Patient comfort and safety are prerequisites for office procedures.
      STUDY OBJECTIVE: comparison of the fentanyl transdermal patch with injection of
      local anesthesia for intraoperative/postoperative pain from in-office
      Thermachoice III ablations. METHODS: Single-center prospective randomized (1:1)
      cohort study. Primary Endpoint: intraoperative and postoperative VAS pain scores
      (0 as no pain, 10 as extreme pain). Secondary Endpoints: patient satisfaction
      between cohorts and adverse events. RESULTS: 41 patients were randomized [21
      patch protocol (FP), 20 injection protocol (IP)]. For patch users, the median VAS
      scores were 2.60 (range 1-4) intraoperatively and 3.30 (range 2-5)
      postoperatively (p = 0.09, CI = -0.8 to 0.4), with the most common adverse events
      being nausea (62%) and vomiting (38%). Compared to injection, there was no
      significant difference in intraoperative VAS score (FP median VAS = 2.60, IP
      median VAS = 2.59; p = 0.15, CI = -0.05 to 0.48), but a significant difference
      postoperatively (FP median VAS = 3.30, IP median VAS = 6.0; p = 0.01, CI = -2.6
      to -1.4). Less NSAIDs were used postoperatively with the FP. At 24 h, more FP
      patients were 'very satisfied' or 'satisfied' than IP patients. CONCLUSION: Patch
      intraoperative VAS pain scores are comparable to uterine block scores;
      postoperative VAS pain scores were statistically lower with the FP. FP resulted
      in more favorable 'satisfaction' rates compared to IP.

PMID- 20029224
TI  - Continuation of metformin reduces early pregnancy loss in obese Pakistani women
      with polycystic ovarian syndrome.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common cause of
      anovulatory infertility worldwide. In addition to a poor conception rate,
      pregnancy loss rates are significantly higher (30-50%) during the first trimester
      in women with PCOS. Insulin resistance (IR) in this syndrome is not only
      implicated toward early pregnancy loss (EPL) but also pathognomic for various
      obstetrical complications during pregnancy. We evaluated the role of Metformin in
      the reduction of EPL in women with PCOS who conceived spontaneously or after
      induction ovulation with or without Metformin. OBJECTIVE: The primary objective
      was to evaluate the effectiveness of Metformin in the reduction of EPL in women
      with PCOS. Secondary outcomes like gestational diabetes, pregnancy-induced
      hypertension and intrauterine growth restriction were also analyzed at the end of
      the study. MATERIAL AND METHODS: This case-control study was conducted from March
      2005 to March 2008 in the infertility and antenatal clinics of the Department of
      Obstetrics and Gynecology of Aga Khan University Hospital, Karachi, Pakistan. A
      total of 197 infertile women with PCOS were included. 'Cases' were women with
      PCOS who conceived while taking Metformin and it whom it was continued throughout
      pregnancy. 'Controls' were women in whom Metformin was either stopped in first
      trimester after confirmation of pregnancy (by serum betaHCG or by ultrasound) or
      they conceived spontaneously without the use of Metformin. RESULTS: All 197 women
      in this study had a confirmed diagnosis of PCOS (Rotterdam criteria). These women
      were followed till the final outcome of pregnancy was achieved. Both groups were
      compared for risk of EPL. It was found that continuation of Metformin during
      pregnancy reduces EPL, i.e. 8.8 vs. 29.4% in cases and controls, respectively (p
      < 0.001). In the subset of women with a prior history of miscarriage, the
      pregnancy loss rate was 12.5% in the Metformin versus 49.4% in control group (p =
      0.002). CONCLUSION: Metformin continuation during pregnancy significantly reduces
      EPL in women with PCOS. IR may play a significant role in EPL.

PMID- 20029225
TI  - Severe transient leukopenia following hysterosalpingography.
AB  - Severe anaphylaxis to contrast media used in hysterosalpingography is very rare.
      Leukopenia may sometimes be seen in severe anaphylaxis associated with shock.
      This case report is about an atypical presentation of anaphylaxis following the
      injection of Conray 280 for hysterosalpingography. The patient had severe
      leukopenia without other associated features of anaphylaxis that resolved
      spontaneously after 48 h. This type of reaction to Conray 280 has not been
      reported before.

PMID- 20029226
TI  - Rank transformation in Haseman-Elston regression using scores for location-scale
      alternatives.
AB  - The Haseman-Elston method is a simple regression approach for detecting genetic
      linkage to quantitative traits in sib-pair studies. Although this method and
      especially the new extended Haseman-Elston approach are quite robust, there might
      be some loss of power for non-normally distributed traits. We propose using rank
      transformation techniques, which either combine the information on a trend in
      locations and in scales or detect a trend only for a subset of the trait
      variables for genetically different sibs under linkage. As this rank
      transformation is based on linear regression, no exact grouping of identity by
      descent proportions has to be assumed. Simulation results indicate a gain in
      power compared to recently suggested nonparametric methods.

PMID- 20029227
TI  - Multiple subsampling of dense SNP data localizes disease genes with increased
      precision.
AB  - BACKGROUND/AIMS: Current linkage studies detect and localize trait loci using
      genotypes sampled at hundreds of thousands of single nucleotide polymorphisms
      (SNPs). Such data should provide precise estimates of trait location once linkage
      has been established. However, correlations between nearby SNPs can distort the
      information about trait location. Traditionally, when faced with this dilemma,
      three approaches have been used: (1) ignore the correlation; (2) approximate the
      correlation; or, (3) analyze a single, approximately uncorrelated subset of the
      original dense data. METHODS: Here, we examine and test a simple and efficient
      estimator of trait location that averages location estimates across random
      subsamples of the original dense data. Based on pairwise estimates of
      correlation, we ensure that the SNPs within each subsample are approximately
      uncorrelated. In addition, we use the nonparametric bootstrap procedure to
      compute narrow, high-resolution candidate gene regions (i.e. confidence intervals
      for the true trait location). RESULTS: Using simulated data, we show that the
      three existing approaches to dense SNP linkage analysis (described above) can
      yield biased and/or inefficient estimation depending on the underlying
      correlation structure. With respect to mean squared error, our estimator
      outperforms the third approach, and is as good as, but usually better than the
      first and second approaches. Relative to the third approach, our estimator led to
      a 47.5% reduction in the candidate gene region length based on the analysis of 15
      hypertension families genotyped at approximately 500,000 SNPs. CONCLUSION: The
      method we developed will be an important tool for constructing high-resolution
      candidate gene regions that could ultimately aid in targeting regions for
      sequencing projects.

PMID- 20029228
TI  - Association Analysis under Population Stratification: A Two-Stage Procedure
      Utilizing Population- and Family-Based Analyses.
AB  - OBJECTIVE: The association analysis based on a population-based case-control
      study is convenient and powerful, but may be biased under population
      stratification (PS), namely the study population consists of strata heterogeneous
      in disease rates and allele frequencies. On the other hand, a family-based (e.g.
      case-parents) study is robust against the PS bias, but may be less convenient to
      implement. We propose an association analysis that preserves the full robustness
      property of the family-based analysis while allowing for borrowing information
      from a population-based analysis. METHODS: A two-stage procedure is proposed. In
      the first stage, one selects a population-based case-control sample and performs
      a traditional case-control association analysis. In the second stage, one
      randomly selects a subset of the first-stage cases and recruits their family
      controls (e.g. parents), and performs a family-based association analysis. An
      overall two-stage analysis is then performed to utilize information from the two
      stages. RESULTS: The proposed two-stage analysis achieves higher power than the
      second-stage family-based analysis by utilizing information in the first-stage
      population study, while maintaining the full robustness of the family study and
      hence is still valid under PS. The proposal can also accommodate parental
      missingness when the case-parents study is used as the second-stage family study.
      CONCLUSION: The two-stage analysis facilitates efficient and robust association
      analysis under PS. Its computation- and cost-effectiveness render it very
      promising in genome-wide association studies.

PMID- 20029229
TI  - Growing news on Noonan and related syndromes.

PMID- 20029230
TI  - Noonan syndrome: introduction and basic clinical features.
AB  - Noonan syndrome (NS) is a fairly common (1 per 1,000-2,500 live births) autosomal
      dominantly inherited disorder and the most common syndromal cause of congenital
      heart disease after Down's syndrome. The clinical features vary with age, but
      typical signs of NS include characteristic facial features with hypertelorism,
      down-slanting palpebral fissures, low-set posteriorly rotated ears, chest and
      spinal deformities, short stature, specific heart defects, learning disabilities
      and mild mental retardation. This article gives a brief introduction to NS and
      its basic clinical features using the established and generally accepted NS
      scoring system based on family history and facial, cardiac, growth, chest wall
      and other criteria. Aspects discussed include the definition, epidemiology,
      etiology, diagnosis and genetics of NS, as well as growth, skeletal and gonadal
      anomalies, pubertal development, ophthalmic and cutaneous abnormalities and the
      incidence of cancer in patients with NS.

PMID- 20029231
TI  - Malignant diseases in Noonan syndrome and related disorders.
AB  - The overall risk of cancer in children with Noonan (NS), cardio-facial-cutaneous,
      Costello or LEOPARD syndrome is high, although no precise estimates are
      available. There are few data on cancer in adults with NS, but the reported
      numbers of malignancies in adults do not seem excessive. Juvenile myelomonocytic
      leukemia (JMML) is a rare aggressive leukemia in young children. A JMML-like
      myeloproliferative disorder has been described in about 30 neonates with NS and
      the PTPN11 mutation. The disorder often regresses spontaneously, but fatal
      complications may occur. A review of the literature indicates an increased risk
      of acute lymphoblastic leukemia and acute myeloid leukemia in NS. Young children
      with Costello syndrome have an extremely high risk of rhabdomyosarcoma, and also
      an increased risk of neuroblastoma and bladder carcinoma. Registry-based studies
      of patients with NS and related disorders diagnosed with molecular genetics and a
      high-quality long-term follow-up are necessary to further estimate the incidence
      of malignancy.

PMID- 20029232
TI  - Neuropsychological and behavioral aspects of Noonan syndrome.
AB  - The current paper introduces concise neuropsychological assessment as an
      essential tool for studying the contribution of cognition and behavior in the
      expression of genetic syndromes, like Noonan syndrome (NS). Cognitive and
      behavioral findings in NS show intelligence scores across a wide range, with a
      mildly lowered average level. Language and motor development are often delayed,
      but no longer dysfunctional in adulthood. Continuing mild problems in selective
      and sustained attention are noted, as well as suboptimal organization skills and
      compromised abilities to structure complex information. These problems seem to
      culminate in learning difficulties, requiring attention for special needs in
      education. It seems that a complex of psychosocial immaturity, alexithymia and
      amenable traits is typical of NS patients. Consequently, psychopathology or
      psychological problems in leading a self-serving life may often remain
      underreported. This is why the authors advocate the integration of the domain of
      social cognition and personality in NS assessment.

PMID- 20029233
TI  - Noonan syndrome: the hypothalamo-adrenal and hypothalamo-gonadal axes.
AB  - The hypothalamo-pituitary-adrenal axis has not been studied systematically in
      Noonan syndrome (NS), despite potential concerns about other aspects of
      hypothalamo-pituitary function. While adrenarche may be delayed in children with
      constitutional growth of puberty and in isolated GH deficiency, this does not
      generally seem to be the case in hypergonadotrophic hypogonadism due to Turner
      syndrome (TS) and this is (anecdotally) the usual hormonal profile in NS children
      and adults. Precocious or 'exaggerated' adrenarche can be associated with
      intrauterine growth retardation and is a forerunner of syndrome X. Although NS
      neonates often have 'normal' birth weights, in some it can be artificially
      inflated by subcutaneous edema (as in TS, where intrauterine growth retardation
      is characteristic). Overall, however, a controlling role for adrenarche (whether
      precocious or delayed) in gonadarche in NS seems unlikely. Neither normally
      descended testes nor normal (even if delayed) pubertal development implies normal
      fertility in NS men. Interactions between fetal, neonatal, childhood and pubertal
      testis development and gonadal axis maturation are complex. There is probably a
      spectrum of abnormalities in NS, but most commonly primary gonadal failure and
      hypergonadotrophic hypogonadism - characteristic NS molecular genetic
      abnormalities - may be important for normal germ cell proliferation, development
      and migration. The identification of different gene defects facilitates
      understanding of NS phenotypic diversity and provides opportunities for
      prospective studies on gonadal and adrenal axes in better defined populations
      less subject to ascertainment bias. At a clinical level, more longitudinal data
      are still needed with regard to the natural history of pubertal timing, its tempo
      of progression and the pattern of pubertal growth.

PMID- 20029234
TI  - Growth in Noonan syndrome.
AB  - Growth failure in Noonan syndrome is mainly postnatal of character and is
      dominated by slow maturation and late puberty. The postnatal early decline seems
      to be an intrinsic part of the syndrome. Reported adult heights are about -2 SD
      and are indicative of a secular trend.

PMID- 20029235
TI  - Noonan syndrome: growth to growth hormone - the experience of observational
      studies.
AB  - Short stature is one of the key features of Noonan syndrome (NS). Attempts have
      therefore been made to improve height by means of recombinant human growth
      hormone (rhGH) treatment. Most of these endeavors were carried out either as case
      studies or observational studies. The overall experience in treating NS is still
      rather limited, and, in general, it can be said that the NS patients who received
      GH treatment represent a very narrow segment. The dosages applied in both the
      case studies and observational studies tended to be higher than those used in the
      replacement therapy of GH-deficient patients, but lower than in Turner syndrome
      patients. The NS studies have shown that the overall height gain of patients is
      small (5-10 cm), and that treatment usually begins at the age of about 10 years,
      at a height of approximately -3.0 SDS. This small response to treatment reflects
      the external treatment conditions (i.e. late age at GH start, low GH dose), but
      may also be associated with the fact that impaired sensitivity to GH is common in
      NS. Both case studies and observational studies are necessary in order to obtain
      further evidence about the efficacy and safety of GH treatment in NS.

PMID- 20029236
TI  - Growth hormone therapy in Noonan syndrome: growth response and characteristics.
AB  - Growth hormone treatment in Noonan syndrome increases growth velocity
      significantly during the first 2 years of treatment and, to some extent, until
      puberty. This increase is more pronounced if treatment is started at an early
      age. Treatment before the age of 5 years is not recommended due to an increased
      risk of malignancies. In contrast to other growth hormone-treated patients, a
      slight but significant further increase in height gain can be expected during
      pubertal growth (at least in boys). Final height improvement varies between 1 and
      2 SDS in different studies. Cardiac function does not seem to be impaired during
      treatment. No significant adverse events have been reported.

PMID- 20029237
TI  - GH therapy in Noonan syndrome: Review of final height data.
AB  - BACKGROUND AND AIMS: Several studies, despite using small cohorts, have shown a
      short-term improvement in the height velocity of short children with Noonan
      syndrome (NS) when treated with recombinant growth hormone (GH). However, the
      question is whether or not this improvement is sustained until adult height is
      reached. This paper reviews the few studies reporting final height data of GH
      treatment in individuals with NS. METHODS: Review of published papers from 4 main
      and several small studies with final height data after GH treatment in NS.
      RESULTS: The range of height gain to adult age varies between 0.6 and 2.0 SDS,
      depending on genotype, age at start of treatment, duration of treatment and which
      growth charts are used. The younger the age at which treatment is started, the
      better the result. There seems to be a correlation between growth response and
      genotype, with a diminished growth response when the PTPN11 mutation is present.
      CONCLUSION: Data on the benefits of GH treatment during childhood and adolescence
      upon the final height are encouraging in individuals with NS. There is a
      substantial height gain during prepubertal years, which continues during the
      pubertal period, reaching a final height within the normal population in the
      majority of previously short individuals with NS.

PMID- 20029238
TI  - Growth hormone and the heart in Noonan syndrome.
AB  - BACKGROUND: The clinical hallmarks of Noonan syndrome (NS) are facial
      dysmorphism, short stature and cardiac defects. As one of the common cardiac
      defects in NS is hypertrophic cardiomyopathy, there have been concerns regarding
      cardiac safety since the start of human growth hormone (hGH) therapy for NS.
      METHODS: Review of currently available data on the prevalence of cardiac defects,
      the theoretical effects of hGH on the heart and the results of studies on the
      effects of hGH on the heart. RESULTS: The prevalence of cardiac defects in NS is
      high, and the spectrum is very broad. Progression of ventricular wall thickness
      during hGH therapy has never been reported. There are barely any data available
      on children with NS and hypertrophic cardiomyopathy collected during hGH therapy.
      In post-marketing surveillance studies, there are no reports of adverse cardiac
      events related to hGH therapy. CONCLUSION: The reported absence of negative
      effects of hGH therapy on the heart in NS and especially on ventricular wall
      thickness is reassuring. Still, keeping in mind the current limited experience,
      any effects on the heart resulting from hGH therapy should be monitored carefully
      in NS.

PMID- 20029239
TI  - Response to growth hormone in short children with Noonan syndrome: correlation to
      genotype.
AB  - Short stature is a major characteristic of Noonan syndrome (NS), the biological
      basis of which is not yet clear. In around half of all individuals with NS, the
      cytoplasmic tyrosine phosphatase SHP2 encoded by PTPN11 is mutated and predicted
      to be overactive. While SHP2 enhances Ras-MAPK signaling, it downregulates
      Jak2/STAT5b signaling of the growth hormone (GH) receptor, according to in vitro
      data. Decreased IGF-I levels have been measured in those children with NS who
      carried PTPN11 mutations suggesting a mode of mild GH insensitivity. The short
      term responsiveness to GH therapy in NS with respect to PTPN11 mutations has been
      addressed in 3 studies in the past. The number of treated children was small and
      gene analysis was restricted to PTPN11, excluding the recent discovered candidate
      genes KRAS, RAF1 and SOS1. All 3 studies showed that GH responsiveness was mildly
      reduced in the presence of PTPN11 mutations; relevant long-term data, however,
      are missing. In a small subgroup of patients with NS, tumor risk is increased and
      related to specific mutations of Ras-MAPK pathway genes, including PTPN11.
      Therefore, when long-term GH therapy is intended to promote growth in children
      with NS, it has to be considered in relation to the genotype, the effective
      promotion of growth and the potentially increased tumor risk. Progress in the
      understanding of cell regulation by Ras-MAPK signaling will hopefully provide
      more evidence on which therapy might be helpful in the care of children with NS.

PMID- 20029240
TI  - Genetic and pathogenetic aspects of Noonan syndrome and related disorders.
AB  - Noonan syndrome (NS) and the clinically overlapping disorders cardio-facio
      cutaneous syndrome, LEOPARD syndrome, Costello syndrome and Neurofibromatosis
      Noonan syndrome share the clinical features of short stature, the same spectrum
      of congenital heart defects, and a similar pattern of craniofacial anomalies. It
      is now known that all these disorders are caused by mutations in components of
      the RAS-MAPK signaling pathway. This pathway was previously known for its
      involvement in tumorigenesis. This article reviews the current knowledge on
      underlying genetic alterations and possible pathogenetic mechanisms responsible
      for NS and related disorders. It discusses the relationship between a group of
      developmental disorders and oncogenes. Potential future treatment prospects are
      based on the possibility of inhibiting RAS-MAPK signaling by pharmaceuticals.

PMID- 20029241
TI  - Expression of the Foxp3 gene in spleen mononuclear cells of a mouse model with
      allergic rhinitis.
AB  - OBJECTIVE: There is growing speculation that the impairment in regulatory-T-cell
      (Treg)-mediated dominant tolerance may play an important role in the pathogenesis
      of allergic rhinitis (AR). The aim of this study was to investigate whether the
      changes in the forkhead transcription factor 3 (Foxp3) gene expression may
      aggravate nasal mucosal inflammation in allergic mice, and whether or not these
      features result from the loss of Tregs. METHODS: AR was induced by both
      intraperitoneal injection and intranasal administration of ovalbumin in BALB/c
      mice, while the control mice were treated with saline. A comparison of the
      frequency of CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells of the
      AR and control mice was made by flow cytometry. Spleen mononuclear cells were
      used for RNA extraction and RT-PCR was used to measure Foxp3 mRNA expression.
      RESULTS: The expression of the Foxp3 gene was significantly reduced in spleen
      mononuclear cells in AR mice compared with the control. Moreover, a significant
      decrease in the percentage of CD4+CD25+Foxp3+ Tregs was exhibited in peripheral
      blood mononuclear cells of AR mice compared with the control mice. CONCLUSION:
      The insufficiency of Tregs and the Foxp3 gene may contribute to the development
      of AR in mice.

PMID- 20029242
TI  - Surgical outcome in patients with oral verrucous carcinoma: long-term follow-up
      in an endemic betel quid chewing area.
AB  - BACKGROUND/AIMS: To evaluate the clinical features and prognosis of patients with
      oral verrucous carcinoma (OVC) in an endemic betel quid chewing area. METHODS: A
      retrospective review was conducted in 39 patients with OVC treated surgically
      from 1991 to 2002. RESULTS: Thirty-seven patients (94.9%) were male. The median
      age at diagnosis was 53.8 years. All patients had been exposed to betel quid,
      cigarette smoking, and/or alcohol. The most common site of tumor origin was the
      buccal mucosa (64.1%). The tumor control rate was 97.4% after the first surgical
      procedure. Second/multiple primary tumors (SPTs/MPTs) were found in 21 patients.
      There were 13 deaths during the follow-up period, with SPTs/MPTs being the most
      common cause. The cancer-specific survival rate was 89.1% at 5 years, but
      continued to decrease thereafter. CONCLUSION: Surgery was effective for
      controlling OVC. However, long-term follow-up was necessary because of the high
      incidence of SPTs/MPTs and its impact on patient survival.

PMID- 20029243
TI  - A double-blind study of zaltoprofen for the treatment of upper respiratory tract
      infection.
AB  - We conducted a double-blind study to evaluate the antipyretic and analgesic
      effects of a single administration of zaltoprofen, a nonsteroidal anti
      inflammatory drug, in patients with acute upper respiratory tract infection. 170
      patients were assigned to one of the 3 treatment groups (80, 160 mg, placebo).
      Changes over time of body temperature and the visual analog scale score of pain
      were measured under the supervision of the study staff at the participating
      medical institutions. A significant decrease in body temperature from the
      baseline value was noted at all measurement points from 0.5 to 6 h after drug
      administration in the zaltoprofen groups. The lowest temperature during the
      observation period was recorded between 3 and 4 h, and the body temperature
      tended to rise at 6 h. No significant decrease in body temperature was noted at
      any time during the observation period in the placebo group. A significant
      decrease in pain scores from the baseline was noted at all measurement points in
      the zaltoprofen groups, and the decrease was maintained even at 6 h. An analgesic
      effect but no antipyretic effect was observed in the placebo group.

PMID- 20029244
TI  - Modification of fentanyl analgesia by antidepressants.
AB  - Clinical practice often requires simultaneous administration of antidepressants
      with opioids (oncology, rheumatology). Coadministration may either attenuate or
      potentiate opioid analgesia. The purpose of this paper was to verify how the
      analgesic action of fentanyl (0.05 mg/kg) is affected by single administration as
      well as 4- or 21-day premedication with antidepressants characterized by various
      mechanisms of action. The effects of amitriptyline 3 mg/kg, moclobemide 5 mg/kg,
      fluoxetine 5 mg/kg and reboxetine 0.08 mg/kg were investigated. Experiments were
      conducted on normotensive Wistar Kyoto rats. The pain threshold was measured
      using an analgesimeter. It was concluded that the single administration of an
      antidepressant increases the analgesic action of fentanyl. Four-day premedication
      with fluoxetine and reboxetine significantly attenuated the antinociceptive
      action of fentanyl, whereas 21-day premedication with all antidepressants
      investigated (fluoxetine, amitriptyline, moclobemide, reboxetine) markedly
      decreased it. The potential clinical importance of this observation is discussed.

PMID- 20029247
TI  - Portrait of Paul M. Wood, M.D.

PMID- 20029248
TI  - Death after initiation of intrathecal drug therapy for chronic pain: assessing
      risk and designing prevention.

PMID- 20029249
TI  - The Cotton-Boothby apparatus.

PMID- 20029250
TI  - Long, Wells, Morton, or Jackson?

PMID- 20029251
TI  - Operation timing does not affect outcome after coronary artery bypass graft
      surgery.
AB  - BACKGROUND: Human factors such as fatigue, circadian rhythms, scheduling, and
      staffing may have an impact on patient care over the course of a day across all
      medical specialties. Research by the transportation industry concludes that human
      performance is degraded by shift work, circadian rhythm disturbances, and
      prolonged duty. This study investigated whether the timing of coronary artery
      bypass graft surgery affects outcomes. METHODS: The outcomes of coronary artery
      bypass graft surgery patients were analyzed according to the hour of the day, day
      of the workweek, month, and moon phase in which the surgery started. All patients
      who underwent isolated coronary artery bypass graft surgery between January 1,
      1993 and July 1, 2006 were considered for the study.The primary outcome
      measurement was a compound morbidity outcome of six variables defined by the
      Society of Thoracic Surgeons. These outcomes included (1) in-hospital death, (2)
      acute postoperative myocardial infarction, (3) neurologic morbidity, including
      focal or global neurologic deficits or death without awakening, (4) serious
      infection morbidity consisting of sepsis syndrome or septic shock, (5) new-onset
      renal failure requiring dialysis, and (6) postoperative ventilatory support
      exceeding 72 h. RESULTS: The composite morbidity and in-hospital mortality rates
      were 4.8% and 1.4%, respectively. The number of cases each weekday, each month of
      the year, and during each phase of the moon were consistent. None of the time
      factors significantly affected the composite morbidity outcome. CONCLUSIONS:
      Elective coronary artery bypass graft surgery can be scheduled throughout the
      workday, any day of the work week and in any month of the year without
      compromising outcome.

PMID- 20029252
TI  - Cordus' synthesis of ether.

PMID- 20029253
TI  - Mortality associated with implantation and management of intrathecal opioid drug
      infusion systems to treat noncancer pain.
AB  - BACKGROUND: In 2006, the authors observed a cluster of three deaths, which
      circumstances suggested were opioid-related, within 1 day after placement of
      intrathecal opioid pumps for noncancer pain. Further investigation suggested that
      mortality among such patients was higher than previously appreciated. The authors
      performed investigations to quantify that mortality and compare the results to
      control populations, including spinal cord stimulation and low back surgery.
      METHODS: After analyzing nine index cases--three sentinel cases and six
      identified by a prospective strategy--the authors used epidemiological methods to
      investigate whether mortality rates reflected patient- or therapy-related
      differences. Mortality rates after intrathecal opioid therapy and spinal cord
      stimulation were derived by correlating Medtronic device registration data with
      de-identified data from the Social Security Death Master File. Aggregate
      demographic and comorbidity data were obtained from Medicare and United
      Healthcare population databases to examine the influence of demographics and
      comorbidities on mortality. RESULTS: Device registration and Social Security
      analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3
      days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality
      than after spinal cord stimulation implants or after lumbar diskectomy in
      community hospitals. Demographic, illness profile, and mortality analyses of
      large databases suggest, despite limitations, that excess mortality was related
      to intrathecal opioid therapy, and could not be fully explained by other factors.
      These findings were consistent with the nine index cases that revealed that
      respiratory arrest caused or contributed to death in all patients. No device
      malfunctions associated with overinfusion were identified among cases where data
      were available. CONCLUSIONS: Patients with noncancer pain treated with
      intrathecal opioid therapy experience increased mortality compared to similar
      patients treated by using other therapies. Respiratory depression as a
      consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug
      interactions is one plausible, but hypothetical mechanism. The exact causes for
      patient deaths and the proportion of those deaths attributable to intrathecal
      opioid therapy remain to be determined. These findings, although based on
      incomplete information, suggest that it may be possible to reduce mortality in
      noncancer intrathecal opioid therapy patients.

PMID- 20029254
TI  - Body mass index: an illogical correlate of obesity.

PMID- 20029255
TI  - Paradigm consciousness: a new approach to understanding anesthesia knowledge and
      education.

PMID- 20029256
TI  - Ventilator-associated pneumonia or endotracheal tube-associated pneumonia or none
      of the above? Lessons learned from laboratory animal studies.

PMID- 20029259
TI  - Endotracheal tube-associated pneumonia.

PMID- 20029260
TI  - Wren, Boyle, and the origins of intravenous injections and the Royal Society of
      London.

PMID- 20029261
TI  - Esmolol may abolish volatile anesthetic-induced postconditioning by scavenging
      reactive oxygen species.

PMID- 20029263
TI  - Goals neither validated nor met in goal-directed colloid versus crystalloid
      therapy.

PMID- 20029268
TI  - It takes two to tango: combined amylin/leptin agonism as a potential approach to
      obesity drug development.
AB  - The discovery of leptin in 1994 was a seminal event in obesity research. It
      helped to establish that body weight is tightly regulated by a complex
      neurohormonal feedback system and that obesity should be viewed as a disorder
      with a strong biological basis rather than simply the result of poor lifestyle
      choices and lack of willpower.Leptin, secreted from adipocytes, acts as a
      prototypic long-term (tonic) adiposity signal. Although nonclinical and clinical
      studies have provided unequivocal evidence that leptin plays a unique, pivotal
      role in body weight regulation, efforts to develop recombinant leptin
      (metreleptin) as a monotherapy for obesity have proven unsuccessful. Amylin,
      secreted from pancreatic beta-cells, fulfills the criteria for a short-term
      (episodic) satiety signal. The amylin analog pramlintide elicits sustained
      reductions in food intake and body weight in obese rodents and humans.A
      translational research program aimed at elucidating the interaction between
      different islet-, gut-, and adipocyte-derived hormones led to the discovery that
      combined amylin/leptin agonism induces marked, synergistic, fat-specific weight
      loss in leptin-resistant diet-induced obese rodents. In obese humans, combination
      treatment with pramlintide/metreleptin led to an approximately 13% weight loss
      after 24 weeks, significantly more than after treatment with pramlintide or
      metreleptin alone.Collectively, these findings suggest that combined
      amylin/leptin agonism may have therapeutic utility as part of an integrated,
      neurohormonal approach to obesity pharmacotherapy.

PMID- 20029271
TI  - HIV-1 seroreversion following antiretroviral therapy in an HIV-infected child
      initially presenting with acquired immunodeficiency syndrome.

PMID- 20029272
TI  - Pharmacokinetics of double-dose raltegravir in two patients with HIV infection
      and tuberculosis.

PMID- 20029274
TI  - Pain relief in the emergency department.

PMID- 20029269
TI  - Central leptin receptor action and resistance in obesity.
AB  - The discovery of leptin in 1994 has led to remarkable advances in obesity
      research. We now know that leptin is a cytokinelike hormone that is produced in
      adipose tissue and plays a pivotal role in regulation of energy balance and in a
      variety of additional processes via actions in the central nervous system. This
      symposium review covers current understandings of neuronal leptin receptor
      signaling and mechanisms of obesity-related leptin resistance in the central
      nervous system and provides recent insights into the regulation of peripheral
      glucose balance by central leptin action in rodents.

PMID- 20029275
TI  - Anal pain: an unusual presentation of ectopic pregnancy.

PMID- 20029276
TI  - Dexmedetomidine for procedural sedation in the emergency department.

PMID- 20029277
TI  - Almost innovation.

PMID- 20029278
TI  - Prevention--what is your strategy?

PMID- 20029280
TI  - Fifteen tips for success in injury prevention.
AB  - Fifteen tips for success in injury prevention include the following: (1) make a
      plan; (2) understand injury epidemiology; (3) read, learn, and get educated; (4)
      show me the data; (5) select prevention strategies thoughtfully; (6) define risk
      factors and understand risk taking; (7) evaluate; (8) schedule a lunch meeting;
      (9) use principles of health behavior change, adult education theory, and
      communication theory; (10) be friends with the marketing and public affairs
      people; (11) recognize the fact that people are more emotional about injury in
      children than in adults; (12) understand cost-benefits and payoffs; (13) get
      stuff; (14) report your results; and (15) be patient. Several useful tables for
      basic references to resources in injury prevention are included.

PMID- 20029281
TI  - Sustainability of an in-home fire prevention intervention.
AB  - Residential fires remain a challenge in many parts of the United States. This
      project assessed the sustainability of a community-based fire prevention
      intervention on household fire safety knowledge and practices. The design was a
      prospective, cohort study including preintervention and postintervention surveys,
      which assessed participants' fire safety knowledge and behavior. The
      implementation of an in-home visit to educate parents of third- and fourth-grade
      students on escape planning coupled with the installation of smoke alarms can be
      successful in increasing basic fire safety knowledge and household fire safety
      practices.

PMID- 20029283
TI  - High-risk adolescent injury prevention: the first program of its kind.
AB  - This article describes the history, development, and growth of Maryland's first
      hospital-based trauma prevention program. It details how the creators of the
      program partnered with multiple community agencies to provide a much-needed
      service for high-risk teens. The program has grown to include a variety of
      prevention education programs reaching people of all ages.

PMID- 20029284
TI  - Including fall prevention for older adults in your trauma injury prevention
      program--introducing Farewell to Falls.
AB  - With data showing that more than 50% of visits to our trauma center for older
      adults 65 years and older are due to falls, injury prevention programs in trauma
      centers should be paying more attention to the area of fall prevention for older
      adults. Farewell to Falls, a free, home-based program of Stanford Hospital and
      Clinic's trauma service, utilizes a multifaceted approach to help reduce falls.
      In addition to improving the lives of seniors, the program fulfills a community
      benefit goal and provides strong hospital marketing opportunities. This program
      is a benefit to hospitals and the older adults they serve.

PMID- 20029285
TI  - A multidisciplinary motorcycle safety initiative.
AB  - Motorcycle registrations are on the rise in the United States, especially among
      riders over 40 years of age. While motorcycle popularity has been increasing, so
      have injuries and fatalities. Unfortunately, motorcycle crashes have been
      increasing at a disproportionately high rate. In 2007, motorcycle fatalities
      reached the highest level since the Department of Transportation began collecting
      data in 1975. Because of the increasing number of motorcycle crashes in Ohio and
      Central Ohio, a multidisciplinary team consisting of the Grant Medical Center's
      trauma program, Franklin County Safe Communities (a Columbus Public Health
      program), the American Motorcyclist Association, and Columbusbiker.com applied
      for and received a $5,000 motorcycle safety mini-grant from the American Public
      Health Association, Public Health Traffic Safety Institute. The mini-grant
      provided funding from October 2008 to September 2009. The 3 goals of the mini
      grant were to promote "sharing the road" with motorcycles, inform the reentry
      riding community on the necessity of proper rider training, and train the Ohio
      injury prevention workforce on motorcycle safety and the motorcycling culture.
      However, the ultimate goal is to prevent death and reduce injury due to
      motorcycle crashes.

PMID- 20029287
TI  - Establishing an injury prevention program to address pediatric pedestrian
      collisions.
AB  - The implementation of a pedestrian safety education program in public schools can
      change the knowledge and beliefs about safe pedestrian behaviors among students
      and their parents or caregivers with the goal of reducing morbidity and mortality
      of children. WalkSafe is a well-established, multiphase pedestrian safety
      intervention program. This program has been shown to improve pedestrian safety
      knowledge of school-aged children in kindergarten through grade 5 after receiving
      a 3-day educational curriculum. A reduction in pediatric pedestrian struck
      injuries is anticipated following program implementation in an urban area with
      significantly increased incidence of such injuries.

PMID- 20029288
TI  - Close the loop on med errors.
AB  - Nurses and pharmacists jointly share an appreciation of the many challenges of
      implementing error-free systems.

PMID- 20029289
TI  - "Mission zero" with smart pumps.
AB  - Implementing this technology can immediately and significantly reduce a
      facility's error rate.

PMID- 20029290
TI  - Extending automation into the OR.
AB  - Explore the merits of this concept for improved medication management.

PMID- 20029291
TI  - Bar coding: what's your role?
AB  - As many as 32% of medication errors occur during administration, so there's good
      reason to find effective methods to minimize these error opportunities.

PMID- 20029292
TI  - Healthcare in the USA: predictions for 2010.

PMID- 20029293
TI  - Embracing the leader in all of us.

PMID- 20029294
TI  - Letter from the president of PSNCB.

PMID- 20029297
TI  - Setting up your office for clinical photography.
AB  - Most clinical photographs utilized in a plastic surgical practice are taken in
      the office setting, primarily to document surgical results. This article will
      discuss the various ways that the office environment can be optimized for
      clinical photography.

PMID- 20029295
TI  - Treatment of skin graft donor sites with a unique transparent absorbent acrylic
      dressing.
AB  - Split-thickness skin grafting is a common plastic surgical procedure to achieve
      quick coverage of a skin deficit, including burn reconstruction, muscle-flap
      coverage, and acute and chronic full-thickness wounds. Despite the varied uses of
      the skin graft, there is always a donor site from which the skin is harvested.
      The focus of our study was the treatment of the donor site.

PMID- 20029299
TI  - Educational program: the nurse's role in educating postmastectomy breast cancer
      patients.
AB  - "You have breast cancer" may be some of the most devastating words a woman may
      hear. Breast cancer is the most common cancer among women and the second leading
      cause of cancer death in women behind lung cancer in the United States ().
      According to ACS, more than 180,000 U.S. women will be diagnosed with breast
      cancer in 2008 and more than 40,000 will die from this disease. Although the
      incidence of breast cancer has increased, death rates are on the decline due to
      early detection and improved treatments ().

PMID- 20029301
TI  - Cosmetic medical treatments: why are we so obsessed with beauty-is it nature or
      nurture?
AB  - Cosmetic medical treatments have become mainstream, and images of beauty surround
      us on television, in magazines, and in advertising. It is no wonder that the
      quest for beauty has become so prevalent. This paper explores why individuals
      choose to undergo cosmetic procedures, and looks at the nature versus nurture
      debate surrounding this phenomenon. It is important for nurses, physicians, nurse
      practitioners, or other healthcare professionals involved in the cosmetic surgery
      field to understand the underlying motivations for choosing to undergo elective
      cosmetic procedures in order to make appropriate choices about their patients'
      care. The first theory in this article is rooted in the "nature" school-of
      thought and explores the evolutionary basis behind the quest for beauty. It shows
      that we may be 'hardwired' to think that our appearance signals our reproductive
      capability (D. B. Sarwer, L. Magee, & V. Clark, 2004) and that human physical
      attractiveness is merely a collection of physical traits that signal fecundity
      and health (V. Swami, C. Greven, & A. Furnham, 2007). The "nurture" concept
      focuses on the second theory, the sociocultural theory, which implies that people
      who choose to use cosmetic medical treatments to enhance their appearance may be
      attempting to increase their self-image or self-perception, improve their social
      relationships, and increase their probability of success across a variety of
      social situations. Other minor theories such as the estrogen theory and the
      psychological theory are discussed, along with implications for practice. All of
      these theories are valuable to the healthcare professional and allow a deeper
      understanding of the psyche of their patients.

PMID- 20029303
TI  - New drugs 09, part 1.
AB  - In this article, you'll learn about 10 new drugs, including: * nebivolol HCl, the
      newest beta-adrenergic blocking agent for hypertension * methylnaltrexone
      bromide, a subcutaneous injection for opioid-induced constipation * alvimopan, a
      selective mu-opioid receptor antagonist to combat postoperative ileus.Unless
      otherwise specified, the information in the following summaries applies to
      adults, not children. Consult the product insert for information about each
      drug's safety during pregnancy and breast-feeding. Also consult a pharmacist, the
      product insert, or a comprehensive drug reference for more details on
      precautions, drug interactions, and adverse reactions for all these drugs.

PMID- 20029305
TI  - New drugs 09, part 2.
AB  - In this article, you'll learn about six new drugs, including: * clevidipine, an
      I.V. antihypertensive for use when oral medication isn't feasible * romiplostim
      and eltrombopag olamine, new agents for chronic immune thrombocytopenic purpura *
      C1 inhibitor (human) for hereditary angioedema. Unless otherwise specified, the
      information in the following summaries applies to adults, not children. Consult
      the package insert for information about each drug's safety during pregnancy and
      breast-feeding. Also consult a pharmacist, the package insert, or a comprehensive
      drug reference for more details on precautions, drug interactions, and adverse
      reactions for all these drugs.

PMID- 20029307
TI  - Getting to the root of medication errors.
AB  - Are you following best practices to prevent errors? Is your facility doing all it
      should? Read these revealing survey responses for answers.

PMID- 20029309
TI  - Plastic surgical nursing practice guidelines: blepharoplasty.

PMID- 20029310
TI  - Flash sterilization.

PMID- 20029311
TI  - Hand-off communication does affect patient safety.
AB  - When there is a cacophony of activity happening all at once, it is difficult to
      find the time for proper hand-offs and the communication that accompanies the
      hand-off. The patient is very often hustled from one department to another and
      from one healthcare professional to another-this in spite of everyone's best
      efforts to keep the patient's "transitions smooth" without any interruptions,
      catastrophes, or other unbidden woe. This article will focus on the need for hand
      off communications that are methodical yet flexible and that promote patient
      safety.

PMID- 20029312
TI  - H1N1 Flu.
AB  - Centers for Disease Control and Prevention, U.S. Department of Health & Human
      Services.

PMID- 20029313
TI  - Connections.

PMID- 20029314
TI  - Remember the people: the emotional side of case management.

PMID- 20029316
TI  - Obesity weight management and bariatric surgery case management programs: a
      review of literature.
AB  - PURPOSE/OBJECTIVES: The proportion of Americans with clinically severe obesity
      has vast implications for the nation's healthcare system since this population
      have twice as many chronic medical conditions as people with normal weight.
      Through the use of review of literature, this article (a) describes the types of
      weight loss programs; (b) reviews the results from studies on effectiveness of
      bariatric surgery; and (c) identifies recommendations for obesity and bariatric
      surgery case management programs. PRIMARY PRACTICE SETTINGS: Disease management
      companies appear to be concentrating on general weight loss strategies associated
      with wellness and other condition-specific disease management products, whereas
      larger national healthcare companies with at-risk and insurance products offer
      specific bariatric surgery management products. Case management programs within
      healthcare systems, health management organizations, and insurance companies are
      frequently faced with the management of individuals with morbid obesity and,
      increasingly, those who are requesting or have undergone bariatric surgery.
      FINDINGS/CONCLUSIONS: Research shows that morbid obesity is a disease that
      remains generally unresponsive to diet and drug therapy but appears to respond
      well to bariatric surgery. Research findings suggest that surgical treatment is
      more effective than pharmacological treatment of weight loss and the control of
      some comorbidities associated with obesity. The number of Americans having weight
      loss surgery increased by 804% between 1998 and 2004, which appears to be a
      driver for the recent development of obesity disease management and bariatric
      surgery case management programs. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      Although the immaturity and lack of studies citing outcomes of obesity disease
      and case management programs limit the identification of best practices based on
      outcomes, emerging practices can be identified and recommendations for case
      management can be formulated. In addition to primary prevention and treatment
      programs for obesity, this article describes program activities in detail for the
      following key areas: (1) identification and engagement; (2) coaching, education,
      and support; (3) collaboration among treating providers; (4) preparation,
      management, and follow-up when bariatric surgery is indicated; (5) aggressive
      follow-up until personal goals are achieved; and (6) outcome measurement.

PMID- 20029318
TI  - Supporting people with disabilities in managing individual budgets: the role of
      support brokers.
AB  - PURPOSE: Nationwide people with disabilities are self-directing their long-term
      care supports through individual budgets. Because these individuals may rely on a
      "support broker" to assist them in making and executing decisions regarding their
      budgets, the interactions between the participant and the support broker can
      influence participant autonomy. PRIMARY PRACTICE SETTING: Massachusetts piloted a
      program for 14 participants to receive individual budgets for home and community
      based services. Central to this pilot were the participant-designated support
      brokers, including home care case managers and peer advocates.
      FINDINGS/CONCLUSIONS: Analysis of data on participants and support brokers
      indicated that the support brokers struggled with when, how, and how much to
      assist participants to self-direct. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      Case managers or other providers assuming the support broker's role will need
      proper training if they are to respond skillfully to challenging situations self
      direction may bring.

PMID- 20029320
TI  - Now is the time.

PMID- 20029319
TI  - Case management in the obstetric clinic setting: providing quality, compassionate
      care, while improving outcomes and reducing costs.

PMID- 20029322
TI  - Is specialized care required for concussive injuries?

PMID- 20029323
TI  - Who needs mentoring in case management?

PMID- 20029324
TI  - On being a case manager for friends and family, part 1.

PMID- 20029325
TI  - Facilitating appropriate return to work: case study of a truck driver.

PMID- 20029327
TI  - Maximizing growth in children after renal transplantation.
AB  - Achieving normal height in children after renal transplantation is a crucial
      issue for both quality of life and self-esteem. The management of growth
      retardation in renal transplant recipients includes adequate nutritional intake,
      correction of acidosis, optimal drug compliance, limited calcineurin inhibitor
      nephrotoxicity, steroid-sparing strategies, and sometimes recombinant human
      growth hormone.

PMID- 20029328
TI  - Impact of reduced nephron mass on cyclosporine- and/or sirolimus-induced
      nephrotoxicity.
AB  - BACKGROUND: We evaluated the impact of reduced nephron mass on nephrotoxicity by
      cyclosporine A (CsA) and/or sirolimus (SRL). METHODS: Renal function was tested
      in salt-depleted rats bearing two kidneys (2K), one kidney, or half a kidney
      (1/2K) and treated for 7 or 28 days with CsA (5 mg/kg) and/or SRL (0.8 mg/kg). We
      also measured the expression of aquaporin-2, sodium/phosphate cotransporter
      (NaPi)-2, paracellin-1, and kidney injury molecule (KIM)-1 by real-time
      polymerase chain reaction. RESULTS: At 7 days in 2K, serum creatinine clearance
      (CrCl) was decreased only in CsA/SRL-treated group (P<0.05) compared with
      controls; in 1/2K, CrCl was decreased in all groups, but most dramatically in
      CsA/SRL group (P<0.05). Extended 28-day therapy worsened CrCl in all 1/2K groups
      (P<0.01). Although the expression of aquaporin-2, NaPi-2, and paracellin-1 mRNAs
      tended to increase in kidneys with a reduced nephron mass, NaPi-2 mRNA levels
      decreased in 1/2K rats exposed to CsA/SRL for 28 days (P<0.05). In contrast, low
      KIM-1 mRNA expression in control 2K rats increased fourfold in untreated 1/2K
      (P<0.05), and 50- to 200-fold in CsA/SRL-treated 1/2K (P=0.01). CONCLUSIONS:
      Nephrotoxicity is significantly worsened by reduced nephron mass, which
      correlates with increased expression of KIM-1 and inhibited expression of NaPi-2.

PMID- 20029329
TI  - Bone marrow-derived cells promote liver regeneration in mice with erythropoietic
      protoporphyria.
AB  - BACKGROUND: Bone marrow transplantation can reverse hepatic protoporphyrin
      accumulation and prevent the hepatobiliary complications characteristic of
      erythropoietic protoporphyria. The aim of this study was to assess the
      recruitment capacity of bone marrow cells in the damaged liver and their possible
      contribution to the improved or recovered hepatic function in a murine model of
      erythropoietic protoporphyria (EPP). METHODS: Lethally irradiated female EPP mice
      were transplanted with bone marrow cells from healthy male mice and were
      monitored during 12 or 36 weeks. Two groups of animals killed 12 weeks after
      transplant were also treated with granulocyte colony-stimulating factor. RESULTS:
      Cell transplantation decreased porphyrin contents in erythrocytes and liver.
      Improved hepatic structure and function and reduced hepatic fibrosis were
      observed, especially 36 weeks after transplant. Bone marrow-derived cells (22%
      35%) were identified in the liver of recipient mice by means of fluorescence in
      situ hybridization (chrY-FISH) or green fluorescent protein staining and were
      characterized by immunofluorescence staining. The livers of recipients contained
      20% to 30% myofibroblasts (alpha-smooth muscle actin-positive cells), 40% CK19
      positive cells, and 10% to 28% hepatocytes (albumin-positive cells) derived from
      the donor bone marrow. CONCLUSIONS: Bone marrow-derived cells play a significant
      role in restoring and regenerating hepatic tissue in EPP mice. Hepatic repair was
      associated with fibrogenesis, enhanced by granulocyte colony-stimulating factor
      treatment, and almost normal liver structure and function was observed in the
      long term (36 weeks posttransplant).

PMID- 20029330
TI  - Transfer of tolerance to collagen type V suppresses T-helper-cell-17 lymphocyte
      mediated acute lung transplant rejection.
AB  - BACKGROUND: Rat lung allograft rejection is mediated by collagen type V (col(V))
      specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is
      sufficient to induce rejection pathology in isografts, whereas tolerance to
      col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T
      cells from tolerant rats could suppress the Th17-mediated rejection in the
      syngeneic model of lung transplantation. METHODS: Rats were subjected to
      syngeneic left lung transplantation, and acute rejection was induced by adoptive
      transfer of lymph node cells from col(V)-immunized rats. Tolerance was induced by
      intravenous injection of col(V), and spleen lymphocytes were used for adoptive
      transfer. CD4+ T cells were depleted using magnetic beads. Lung isografts were
      analyzed using micro-positron emission tomography imaging and histochemistry. The
      transvivo delayed type hypersensitivity assay was used to analyze the Th17
      response. RESULTS: Adoptive cotransfer of col(V)-specific effector cells with
      cells from col(V)-tolerized rats suppressed severe vasculitis and bronchiolitis
      with parenchymal inflammation, and the expression of interleukin (IL)-17
      transcripts in mediastinal lymph nodes induced by effector cells alone. Analysis
      by transvivo delayed type hypersensitivity showed that the reactivity to col(V)
      was dependent on the presence of tumor necrosis factor-alpha and IL-17 but not
      interferon-gamma. Depletion of CD4+ T cells from the suppressor cell population
      abrogated the col(V)-specific protection. CONCLUSION: Th17-mediated acute
      rejection after lung transplantation is ameliorated by CD4+ col(V)-specific
      regulatory T cells. The mechanism for this Th17 suppression is consistent with
      tolerance induction to col(V). The goal of transplantation treatment, therefore,
      should target Th17 development and not suppression of T-cell activation by
      suppressing IL-2.

PMID- 20029331
TI  - Bortezomib can suppress activation of rapamycin-resistant memory T cells without
      affecting regulatory T-cell viability in non-human primates.
AB  - BACKGROUND: Memory T cells specific for donor antigens are currently recognized
      as a significant barrier for maintaining a successful transplant. Furthermore, it
      has been shown that commonly used immunosuppressive drugs do not alleviate this
      memory response. Here, we report that rapamycin allows significant proliferation
      of memory T cells and bortezomib can abrogate the proliferation of rapamycin
      resistant memory T cells when preserving the survival of regulatory T cells.
      METHODS: Peripheral blood mononuclear cells freshly isolated from non-human
      primates were stimulated with anti-CD3/CD28 antibodies, and inhibitory and
      apoptotic effects of rapamycin and bortezomib on memory T-cell proliferation were
      investigated. The CD95 marker in CD3+ T cells was used for the separate
      enrichment of memory T cells and naive T cells. RESULTS: Rapamycin at the level
      even higher than therapeutic concentration could not suppress the proliferation
      of a significant proportion of memory T cells. However, the combined
      administration of bortezomib and rapamycin abrogated the proliferation of
      rapamycin-resistant memory T cells. Furthermore, bortezomib preserved the
      survival of preexisting CD4+ FoxP3+ regulatory T cells, while inducing apoptosis
      of CD4+ FoxP3- conventional T cells. The combined administration of low doses of
      rapamycin and bortezomib also exerted an additive effect on suppressing T-cell
      proliferation. Cytokine analysis demonstrated that bortezomib could not only
      suppress rapamycin-permissive interleukin (IL)-6 production, but also production
      of interferon (IFN)-gamma, IL-4, and IL-10. CONCLUSIONS: This article provides in
      vitro data from which immunosuppressive regimens for the effective control of
      memory T cells in non-human preclinical experiments and in clinical trials are
      selected.

PMID- 20029332
TI  - Induction of regulatory T cells and indefinite survival of fully allogeneic
      cardiac grafts by ursodeoxycholic acid in mice.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) has been used to treat patients with
      cholestatic and autoimmune liver diseases. Several studies have addressed whether
      UDCA can inhibit graft rejection in experimental and clinical transplantation,
      but the results have varied. We investigated the effect of UDCA and the mechanism
      of its effect on alloimmune responses in a murine model of cardiac
      transplantation. METHODS: CBA mice underwent transplantation of a C57BL/10 heart
      and received a single dose of UDCA. Survival times of the allografts were
      recorded. An adoptive transfer study was conducted to determine whether
      regulatory cells were generated. The effects on graft survival of adding FK506 or
      cyclosporine A (CyA) to UDCA treatment were assessed. Histologic, cell
      proliferation, and cytokine assessments were performed. RESULTS: CBA recipients
      given UDCA (25 mg/kg) had indefinite allograft survival (median survival time
      [MST], >100 days). UDCA also suppressed proliferation of splenocytes and
      production of interleukin (IL)-2, IL-6, and interferon-gamma, and up-regulated IL
      10 production. Adoptive transfer of either whole splenocytes or CD4+ cells from
      UDCA-treated allograft recipients resulted in indefinite survival of allografts
      in naive secondary recipients (MST, >100 days). Adoptive transfer of CD4+ CD25+
      cells from UDCA-treated recipients significantly prolonged allograft survival in
      naive secondary recipients (MST, >80 days). FK506 (0.1 mg/kg/day) was compatible
      with the induction of indefinite allograft survival by UDCA, whereas CyA (10
      mg/kg/day) abrogated the effect of UDCA. CONCLUSION: UDCA induced
      unresponsiveness to fully allogeneic cardiac allografts and generated CD4+ CD25+
      regulatory cells in our model. FK506, but not CyA, was compatible with UDCA
      treatment.

PMID- 20029333
TI  - A study of renal outcomes in African American living kidney donors.
AB  - BACKGROUND: Little is known about the long-term outcomes of African American
      living kidney donors (AALKDs). We undertook this study to describe renal outcomes
      of AALKDs several years after donation. METHODS: We invited 107 AALKDs to come
      for follow-up health evaluation. RESULTS: Thirty-nine subjects (36.4%) completed
      evaluation at a mean of 7.1+/-1.6 (range, 3.9-10.2) years postdonation. The mean
      estimated glomerular filtration rate using the abbreviated Modification of Diet
      in Renal Disease equation [eGFR(MDRD)] at follow-up was 72.1+/-16.3 (range, 42
      106) mL/min/1.73 m2, and 18% of subjects had an eGFR(MDRD) of 30 to 59. The mean
      absolute and relative decrease in eGFR(MDRD) from the time of donation to follow
      up was 30.5+/-16.4 mL/min/1.73 m2 and 28.8%, respectively. Subjects whose body
      mass index was more than or equal to 35 kg/m2 (n=8) were found to have a greater
      decrement in e(MDRD) than those with body mass index less than 35 kg/m2 (40.1+/
      7.3 and 28.3+/-17.1 mL/min/1.73 m2, respectively; P=0.009). Sixteen (41%) were
      hypertensive at follow-up, as defined as treatment with antihypertensive
      medications (n=8) or average blood pressure of more than or equal to 140 systolic
      or 90 mm Hg diastolic (n=10, of whom two were on antihypertensive medications).
      One subject had macroalbuminuria (>300 microg/mg creatinine), and six (15.4%) had
      microalbuminuria (30-300 microg/mg creatinine). CONCLUSIONS: AALKDs experience a
      substantial incidence of hypertension and a modest drop in eGFR(MDRD)
      postdonation, and obesity may increase the magnitude of renal decline. Further
      study is urgently needed to determine the long-term risks of AALKDs.

PMID- 20029334
TI  - Effect of hemodialysis before transplant surgery on renal allograft function--a
      pair of randomized controlled trials.
AB  - BACKGROUND: Hemodialysis immediately before kidney transplant surgery has been
      suggested to adversely affect early graft function. On the other hand,
      considering its profound antiinflammatory effects, a beneficial impact of
      regional citrate anticoagulation on the evolution of graft function can be
      speculated. We sought to assess the clinical impact of preoperative hemodialysis
      and dialysis anticoagulation in two related randomized trials. METHODS: Eligible
      kidney transplant candidates with a serum potassium less than or equal to 5.0
      mEq/L were randomized to receive dialysis or no dialysis before deceased donor
      transplantation. Patients with a potassium more than 5.0 mEq/L were randomized to
      receive dialysis with heparin or citrate anticoagulation. The primary endpoint
      was the estimated glomerular filtration rate (eGFR) at posttransplant day 5.
      RESULTS: The first comparison (56 vs. 54 patients) revealed no effect of dialysis
      on eGFR at day 5 (primary endpoint, 12 [interquartile range 5-36] vs. 13 [5-37]
      mL/min/1.73 m2, P=0.98), rates of delayed graft function (22% vs. 27%, P=0.66),
      cellular rejection (20% vs. 24%, P=0.65), and C4d-positive dysfunction (2% vs.
      9%, P=0.11) or 1-year death-censored graft survival (89% vs. 91%, P=0.51).
      Comparing citrate with heparin anticoagulation (44 vs. 66 patients), no
      differences in eGFR at day 5 (17 [8-31] vs. 14 [6-38] ml/min/1.73 m2, P=0.57),
      delayed graft function (21% vs. 30%, P=0.28), cellular rejection (23% vs. 33%,
      P=0.29), and graft survival (90% vs. 88%, P=0.44) were found. For citrate
      anticoagulation, less C4d-positive rejection episodes (P=0.08) and higher 1-year
      eGFR levels (P=0.03) were observed. CONCLUSION: Pretransplant hemodialysis and
      anticoagulation may not affect early graft function in a meaningful way.

PMID- 20029335
TI  - Donor and recipient contribution to transplant vasculopathy in chronic renal
      transplant dysfunction.
AB  - BACKGROUND: Chronic transplant dysfunction is the leading cause of long-term
      renal allograft loss. One of the histologic hallmarks of chronic transplant
      dysfunction is transplant vasculopathy characterized by accumulation of smooth
      muscle cells (SMCs) in the arterial subendothelial space, leading to ischemic
      graft failure. Currently, no therapy is available for transplant vasculopathy,
      and knowledge of the origin (donor vs. recipient) of neointimal cells may
      contribute to develop adequate strategies. METHODS: Origin of neointimal SMCs,
      endothelial, and tubular cells was determined in four nephrectomy samples from
      male recipients transplanted with a female kidney. Recipient-derived cells were
      detected using X- and Y-chromosome-specific fluorescent in situ hybridization
      combined with immunofluorescent staining. Specificity and sensitivity of
      fluorescent in situ hybridization were determined with corresponding controls.
      RESULTS: No Y-chromosome-positive cells were detected in the female to female
      graft, whereas approximately 31% of nucleated cells in male to male grafts had a
      detectable Y-chromosome. In female to male grafts, a recipient-derived population
      of neointimal alpha-smooth muscle actin-positive SMCs were detected (6%, range 3%
      11%). Percentages of recipient-derived arterial endothelial cells, glomerular
      endothelial cells, and tubular epithelial cells were 14% (range 4%-32%), 19%
      (range 7%-31%) and 3% (range 2%-5%), respectively. CONCLUSIONS: Both donor- and
      recipient-derived cells contribute to vascular remodeling in clinical renal
      transplantation. The presence of alpha-smooth muscle actin in donor- and
      recipient-derived cells supports a constructive role for these cells in
      neointimal formation. However, the predominance of donor-derived cells in the
      neointima points to these cells as the likely therapeutic target.

PMID- 20029336
TI  - HLA class I (ABC) upregulation on peripheral blood CD3+/CD8+ T lymphocyte surface
      is a potential predictor of acute rejection in renal transplantation.
AB  - BACKGROUND: Renal transplantation is currently the prevalent therapy for most
      patients with end-stage renal disease. No clinical markers for such rejection
      have been universally accepted. We aimed to investigate the possibility of use of
      human leukocyte antigen (HLA) class I (ABC) on peripheral blood CD3+/CD8+ T
      lymphocytes as a marker of acute rejection. METHODS: For recipients undergoing
      renal transplantation from September 2007 to November 2008, peripheral blood
      samples were obtained pretransplantation and at days 3 and 7 posttransplantation
      when the patients were still hospitalized and at weeks 2 and 3 and months 1, 2,
      3, and 6 posttransplantation. For patients with fever, lumbodynia, gross
      hematuria, or oliguria after transplantation, blood samples were collected
      immediately before and at days 3 and 7 after the administration of anti
      inflammatory regents. The level of HLA class I (ABC) on peripheral-blood
      CD3+/CD8+ T lymphocytes was measured on flow cytometry. RESULTS: For the 79
      transplant recipients, the level of HLA class I (ABC) on peripheral-blood
      CD3+/CD8+ T lymphocytes was consistently elevated during the first 3 weeks after
      transplantation, declined gradually to pretransplantation levels, then tapered
      off and remained stable. Patients experiencing acute rejection (AR) or not after
      transplantation did not differ in level of HLA class I (ABC) up to 6-month follow
      up, except at days 14 and 21 after transplantation, when the level was higher for
      patients experiencing AR (P<0.01). CONCLUSIONS: Upregulation of HLA class I (ABC)
      on peripheral-blood CD3+/CD8+ T lymphocytes could be used as an accurate and
      reliable predictor of AR after renal transplantation.

PMID- 20029337
TI  - Immunosuppressive regimen influences incidence of skin cancer in renal and
      pancreatic transplant recipients.

PMID- 20029338
TI  - Anti-human leukocyte antigen antibodies and development of graft failure after
      renal transplantation.

PMID- 20029339
TI  - Vitacyte collagenase HA: a novel enzyme blend for efficient human islet
      isolation.

PMID- 20029341
TI  - Changing cardiac arrest and hospital mortality rates through a medical emergency
      team takes time and constant review.
AB  - OBJECTIVE: To determine the long-term impact of a medical emergency team on
      survival and to assess the utility of administrative data to monitor outcomes.
      DESIGN: Prospective study of cardiac arrests and survival. Retrospective study of
      administrative data. SETTING: University affiliated tertiary referral hospital in
      Melbourne, Australia. PATIENTS: All patients admitted to hospital in three 6
      month periods between 2002-2007 (prospective) and 1993-2007 (retrospective).
      INTERVENTION: Implementation of a medical emergency team in November 2002.
      MEASUREMENTS AND MAIN RESULTS: In the prospective analysis, rates of unexpected
      cardiac arrest and hospital mortality (referenced to 1000 patient-care days) were
      measured before (July-August 2002) and after (December 2002-May 2003, December
      2004-May 2005, December 2006-May 2007) the introduction of the medical emergency
      team. Cardiac arrest rates decreased progressively from 0.78 per 1000 (95%
      confidence interval, 0.50-1.16) to 0.25 per 1000 (95% confidence interval, 0.15
      0.39, p < .001), and hospital mortality from 0.58 per 1000 (95% confidence
      interval, 0.35-0.92) to 0.30 per 1000 (95% confidence interval, 0.20-0.46, p <
      .05); cardiac arrest rates achieved statistical significance at 2 yrs and
      hospital mortality at 4 yrs. Using administrative data adjusted for age, sex,
      case-mix, and comorbidity, hazard ratios for mortality for the three post
      implementation periods were statistically lower than for the 10 yrs pre
      implementation (0.85, 0.74, 0.65). The intensity of calling (calls/1000 patient
      days) inversely correlated with cardiac arrest rate, unexpected mortality rate,
      and total hospital mortality rate. CONCLUSIONS: The introduction of a medical
      emergency team was associated with a progressive decline of unexpected cardiac
      arrests within 2 yrs, and of unexpected mortality within 4 yrs. This suggests
      that changes to organizational practice take time and benefits may not be
      immediately obvious. Such changes are reflected in total hospital mortality
      measured from administrative data and make monitoring simpler in the longer term.
      Finally, efforts to increase calling of emergency teams should reduce cardiac
      arrests and mortality.

PMID- 20029340
TI  - Cyclooxygenase-2 inhibition provides lasting protection against neonatal hypoxic
      ischemic brain injury.
AB  - OBJECTIVE: To investigate whether inhibition of cyclooxygenase-2, a critical
      component of the inflammatory pathway, is neuroprotective in a neonatal rat model
      of cerebral hypoxia-ischemia. The development of brain inflammation largely
      contributes to neonatal brain injury that may lead to a lifetime of neurologic
      deficits. DESIGN: Laboratory investigation. SETTING: University research
      laboratory. SUBJECTS: Postnatal day ten Sprague-Dawley rats. INTERVENTIONS:
      Neonatal hypoxia-ischemia was induced by ligation of the right common carotid
      artery followed by 2 hrs of hypoxia (8% oxygen). The pups in treatment groups
      were administered 10 mg/kg (low dose) or 30 mg/kg (high dose) of a known
      selective cyclooxygenase-2 inhibitor (NS398). Animals were euthanized at three
      time points: 72 hrs, 2 wks, or 6 wks. Inflammation outcomes were assessed at 72
      hrs; brain damage was assessed at 2 wks and 6 wks along with other organs (heart,
      spleen). Detailed neurobehavioral examination was performed at 6 wks.
      MEASUREMENTS AND MAIN RESULTS: Pharmacologic inhibition of cyclooxygenase-2
      markedly increased survivability within the first 72 hrs compared with untreated
      rats (100% vs. 72%). Low- and high-dose NS398 significantly attenuated the loss
      of brain and body weights observed after hypoxia-ischemia. Neurobehavioral
      outcomes were significantly improved in some parameters with low-dose treatment,
      whereas high-dose treatment consistently improved all neurologic deficits.
      Immunohistochemical results showed a marked decrease in macrophage, microglial,
      and neutrophil abundance in ipsilateral hemisphere of the NS398-treated group
      along with a reduction in interleukin-6 expression. CONCLUSIONS: Selective
      cyclooxygenase-2 inhibition protected neonatal rats against death, progression of
      brain injury, growth retardation, and neurobehavioral deficits after a hypoxic
      ischemic insult.

PMID- 20029342
TI  - Reduced L-type calcium current in ventricular myocytes from pigs with
      hyperdynamic septic shock.
AB  - OBJECTIVE: To hypothesize that reduced L-type calcium current with consequent
      shortening of cardiac repolarization is present in a clinically relevant porcine
      model of hyperdynamic septic shock. Myocardial depression is a well-recognized
      manifestation of sepsis and septic shock. Reduction of L-type calcium current was
      demonstrated to contribute to the myocardial depression in endotoxemic rodents.
      DESIGN: Laboratory animal experiments. SETTING: Animal research laboratory at a
      university. SUBJECTS: Twenty-two domestic pigs of either gender. INTERVENTIONS:
      In anesthetized, mechanically ventilated, and instrumented pigs, sepsis was
      induced by bacteremia (central venous infusion of live Pseudomonas aeruginosa)
      and continued for 22 hrs. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram was
      recorded before and 22 hrs after induction of bacteremia. RR, QT, and QTc
      intervals were significantly shortened by sepsis. In vitro, action potentials
      were recorded in right ventricular trabeculae. Action potential durations were
      shortened in septic preparations. Tumor necrosis factor-alpha did not influence
      action potential durations. L-type calcium current was measured in isolated
      ventricular myocytes. Peak L-type calcium current density was reduced in myocytes
      from septic animals (8.3 +/- 0.4 pA/pF vs. 11.2 +/- 0.6 pA/pF in control). The
      voltage dependence of both L-type calcium current activation and inactivation was
      shifted to more negative potentials in myocytes from septic animals. Action
      potential-clamp experiments revealed that the contribution of L-type calcium
      current to the septic action potential was significantly diminished. In cardiac
      myocytes incubated with tumor necrosis factor-alpha, L-type calcium current was
      not further affected. CONCLUSIONS: In a clinically relevant porcine model,
      hyperdynamic septic shock induced shortening of ventricular repolarization and
      reduction of L-type calcium current. The contribution of L-type calcium current
      to the action potential in septic ventricular myocytes was significantly
      diminished. Tumor necrosis factor-alpha probably did not contribute to this
      effect.

PMID- 20029343
TI  - Bundled care for septic shock: an analysis of clinical trials.
AB  - CONTEXT: Sepsis bundles have been developed to improve patient outcomes by
      combining component therapies. Valid bundles require effective components with
      additive benefits. Proponents encourage evaluation of bundles, both as a whole
      and based on the performance of each component. OBJECTIVE: Assess the association
      between outcome and the utilization of component therapies in studies of sepsis
      bundles. DATA SOURCE: Database searches (January 1980 to July 2008) of PubMed,
      Embase, and the Cochrane Library, using the terms sepsis, bundles, guidelines,
      and early goal directed therapy. DATA EXTRACTION: Inclusion required comparison
      of septic adults who received bundled care vs. nonprotocolized care. Survival and
      use rates for individual interventions were abstracted. MAIN RESULTS: Eight
      unblinded trials, one randomized and seven with historical controls, were
      identified. Sepsis bundles were associated with a consistent (I2 = 0%, p = .87)
      and significant increase in survival (odds ratio, 1.91; 95% confidence interval,
      1.49-2.45; p < .0001). For all studies reporting such data, there were consistent
      (I2 = 0%, p > or = .64) decreases in time to antibiotics, and increases in the
      appropriateness of antibiotics (p < or = .0002 for both). In contrast,
      significant heterogeneity was seen across trials for all other treatments
      (antibiotic use within a specified time period; administration of fluids,
      vasopressors, inotropes, and packed red blood cells titrated to hemodynamic
      goals; corticosteroids and human recombinant activated protein C use) (all I2 >
      or = 67%, p < .002). Except for antibiotics, sepsis bundle components are still
      being investigated for efficacy in randomized controlled trials. CONCLUSION:
      Bundle use was associated with consistent and significant improvement in survival
      and antibiotic use. Use of other bundle components changed heterogeneously across
      studies, making their impact on survival uncertain. However, this analysis should
      be interpreted cautiously as these studies were unblinded, and only one was
      randomized.

PMID- 20029344
TI  - Evolution of the coronary care unit: clinical characteristics and temporal trends
      in healthcare delivery and outcomes.
AB  - OBJECTIVE: To describe long-term temporal trends in patient characteristics,
      processes of care, and in-hospital outcomes among unselected admissions within
      the contemporary coronary care unit. DESIGN: Hospital administrative database
      that records both payment and operation data. SETTING: Coronary care unit of a
      large, academic, tertiary-care medical institution. PATIENTS: A total of 29,275
      patients admitted from January 1, 1989 through December 31, 2006. INTERVENTIONS:
      Unadjusted time-trend plots were created for all variables of interest, and
      multivariable modeling of coronary care unit death was performed. MEASUREMENTS
      AND MAIN RESULTS: Temporal trends in Coronary Care Unit and in-hospital
      mortality, length-of-stay, demographic characteristics, discharge diagnoses,
      Coronary Care Unit procedures, and Charlson comorbidity scores were evaluated.
      Admission severity increased significantly over time (p < .001), but hospital
      length-of-stay decreased (p < .001). The proportion of coronary care unit
      admissions with non-ST-segment elevation myocardial infarction increased (p <
      .001), whereas ST-segment elevation myocardial infarction decreased (p < .001).
      The prevalence of non-cardiovascular diagnoses increased, with the rate greatest
      for comorbid critical illnesses, including sepsis, acute kidney injury, and
      respiratory failure (all p < .001). The use of non-cardiac procedures, such as
      mechanical ventilation and central venous catheterization, also increased over
      time (p < .001). Unadjusted coronary care unit and in-hospital mortality did not
      change during the study period, although death did decrease in the adjusted
      setting. CONCLUSIONS: Substantial changes have occurred over time in patient
      characteristics, diagnoses, and procedures within the coronary care unit of a
      large, academic medical center. In particular, there have been significant
      increases in noncardiovascular critical illness, the results of which may be
      influencing patient outcomes. These findings underscore an existing need to
      clarify the role of the coronary care unit in contemporary cardiovascular care
      and to develop strategies for optimal training, staffing, and clinical
      investigation.

PMID- 20029345
TI  - Different assessment tools for intensive care unit delirium: which score to use?
AB  - OBJECTIVE: To compare validity and reliability of three instruments for detection
      and assessment of delirium in intensive care unit (ICU) patients. Delirium in
      critically ill patients is associated with higher mortality, prolonged duration
      of ICU stay, and greater healthcare costs. Currently, there are several
      assessment tools available for detection of delirium, but only a few of these
      assessment systems are developed specifically to screen for delirium in ICU
      patients. DESIGN: Prospective cohort study. SETTING: ICU at a university
      hospital. PATIENTS: A total of 156 surgical patients aged > or = 60 yrs
      consecutively admitted to the ICU, with a length of stay of at least 24 hrs.
      MEASUREMENTS AND MAIN RESULTS: This study was approved by the institutional
      ethics committee. Trained staff members performed daily and independently the
      Confusion Assessment Method for the ICU (CAM-ICU), the Nursing Delirium Screening
      Scale (Nu-DESC), and the Delirium Detection Score (DDS). These evaluations were
      compared against the reference standard conducted by a delirium expert (blinded
      to the study), who used delirium criteria from the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition (DSM-IV). Of 156 patients, 63 (40%)
      were identified as delirious by the reference standard during the study. Using
      the CAM-ICU and the Nu-DESC, we measured comparable sensitivities (CAM-ICU, 81%;
      Nu-DESC, 83%). The specificity of the CAM-ICU was significantly higher than that
      of the Nu-DESC (96% vs. 81%, p < .01). In contrast, the DDS showed poor
      sensitivity (30%), whereas the specificity was significantly higher compared with
      the Nu-DESC (DDS, 91%; Nu-DESC, 81%, p < .05). The interrater reliability was
      "almost perfect" for the CAM-ICU (kappa = 0.89) and "substantial" for DDS and Nu
      DESC (kappa = 0.79, 0.68). CONCLUSION: The CAM-ICU showed the best validity of
      the evaluated scales to identify delirium in ICU patients. The Nu-DESC might be
      an alternative tool for detection of ICU delirium. The DDS should not be used as
      a screening tool.

PMID- 20029346
TI  - Hemoperfusion with a high-mobility group box 1 adsorption column can prevent the
      occurrence of hepatic ischemia-reperfusion injury in rats.
AB  - OBJECTIVE: High-mobility group box 1, a ubiquitous nonhistone chromosomal
      protein, is passively released from necrotic cells and actively secreted by
      inflammatory cells. Extracellular high-mobility group box 1 has recently been
      recognized to be a mediator of hepatic ischemia-reperfusion injury; however, the
      kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion and the
      role of high-mobility group box 1 in ischemia-reperfusion injury still remain
      poorly understood. This study was designed to assess the localization and the
      kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion injury
      and the effects of high-mobility group box 1 adsorption column in hepatic
      ischemia-reperfusion injury. DESIGN: A prospective, randomized animal study.
      SETTING: University medical center research laboratory. SUBJECTS: Male Sprague
      Dawley rats. INVESTIGATION: The animals underwent 70% partial hepatic ischemia
      for 60 or 90 mins and were then reperfused. To investigate the high-mobility
      group box 1 levels in the serum and in the liver, the animals were killed at
      predetermined periods. As a lethal model, global hepatic ischemia-reperfusion was
      induced by portal triad cross-clamping for 30 mins. Hemoperfusion therapy using a
      cellulofine sulfate bead column (high-mobility group box 1 adsorption column) was
      performed during global hepatic ischemia. MEASUREMENTS AND MAIN RESULTS: During
      60 mins of 70% hepatic ischemia, nuclear high-mobility group box 1 was
      translocated to the cytoplasm in hepatocytes; however, serum high-mobility group
      box 1was not increased. Immediately after reperfusion, the serum high-mobility
      group box 1 was significantly increased (p < .05). High-mobility group box 1
      mediated ischemia-reperfusion injury in not only liver but also the remote organ,
      lung. Removal of excess high-mobility group box 1 in blood using an adsorption
      column significantly improved animal survival (p < .03) and liver and lung
      injuries. CONCLUSIONS: High-mobility group box 1 plays an important role in the
      systemic as well as local pathogenesis of hepatic ischemia-reperfusion injury.
      The removal of excessive high-mobility group box 1 with adsorption column was
      beneficial and promising option in ischemia-related liver injuries.

PMID- 20029348
TI  - A tale of Lutes and Ouds: time to play together in the same key?

PMID- 20029347
TI  - Expanding the paradigm of the physician's role in surrogate decision-making: an
      empirically derived framework.
AB  - BACKGROUND: Little is known about what role physicians take in the decision
      making process about life support in intensive care units. OBJECTIVE: To
      determine how responsibility is balanced between physicians and surrogates for
      life support decisions and to empirically develop a framework to describe
      different models of physician involvement. DESIGN: Multi-centered study of audio
      taped clinician-family conferences with a derivation and validation cohort.
      SETTING: Intensive care units of four hospitals in Seattle, Washington, in 2000
      to 2002 and two hospitals in San Francisco, California, in 2006 to 2008.
      PARTICIPANTS: Four hundred fourteen clinicians and 495 surrogates who were
      involved in 162 life support decisions. RESULTS: In the derivation cohort (n = 63
      decisions), no clinician inquired about surrogates' preferred role in decision
      making. Physicians took one of four distinct roles: 1) informative role (7 of 63)
      in which the physician provided information about the patient's medical
      condition, prognosis, and treatment options but did not elicit information about
      the patient's values, engage in deliberations, or provide a recommendation about
      whether to continue life support; 2) facilitative role (23 of 63), in which the
      physician refrained from providing a recommendation but actively guided the
      surrogate through a process of clarifying the patients' values and applying those
      values to the decision; 3) collaborative role (32 of 63), in which the physician
      shared in deliberations with the family and provided a recommendation; and 4)
      directive role (1 of 63), in which the physician assumed all responsibility for,
      and informed the family of, the decision. In 10 out of 20 conferences in which
      surrogates requested a recommendation, the physician refused to provide one. The
      validation cohort revealed a similar frequency of use of the four roles, and
      frequent refusal by physicians to provide treatment recommendations. CONCLUSIONS:
      There is considerable variability in the roles physicians take in decision-making
      about life support with surrogates but little negotiation of desired roles. We
      present an empirically derived framework that provides a more comprehensive view
      of physicians' possible roles.

PMID- 20029349
TI  - Clinical research ethics for critically ill patients: a pandemic proposal.
AB  - Pandemic H1N1 influenza is projected to be unprecedented in its scope, causing
      acute critical illness among thousands of young otherwise healthy adults, who
      will need advanced life support. Rigorous, relevant, timely, and ethical clinical
      and health services research is crucial to improve their care and outcomes.
      Studies designed and conducted during a pandemic should be held to the same high
      methodologic and implementation standards as during other times. However, unique
      challenges arise with the need to conduct investigations as efficiently as
      possible, focused on the optimal outcome for the individual patient, while
      balancing the need for maximal societal benefit. We believe that clinical
      critical care research during a pandemic must be approached differently from
      research undertaken under nonemergent circumstances. We propose recommendations
      to clinical investigators and research ethics committees regarding clinical and
      health services research on pandemic-related critical illness. We also propose
      strategies such as expedited and centralized research ethics committee reviews
      and alternate consent models.

PMID- 20029351
TI  - Minimally invasive thyroidectomy: state of the art.

PMID- 20029350
TI  - Influenza epidemiology--past, present, and future.
AB  - In April 2009, Mexican, American, and Canadian authorities announced that a novel
      influenza virus with pandemic potential had been identified in large segments of
      the population. Within weeks, it became apparent that the world was dealing with
      the first influenza pandemic in >40 yrs. Despite the unpredictable nature of
      influenza severity and spread in the pandemics of the 20th century, understanding
      the epidemiology of the past pandemics and current influenza pandemic will help
      prepare physicians, hospitals, and governments to predict and prepare for the
      subsequent waves and subsequent pandemics. We present a summary of the biology
      that predisposes influenza to cause sudden pandemics, as well as a summary of the
      epidemiology of the 20th century pandemics. We also report on the epidemiology,
      disease severity, and risk factors for severe disease and intensive care
      admission from the first wave of the current pandemic (April-August 2009). Last,
      we provide a mathematical model based on transmission dynamics of the H1N1
      influenza virus that may provide some guidance in terms of disease incidence and
      hospital impact.

PMID- 20029352
TI  - The role of liver surgery in the treatment of non-colorectal non-neuroendocrine
      metastases (NCRNNE). Analysis of 134 resected patients.
AB  - AIM: The aim of this study was to evaluate the role of surgery in the treatment
      of non-colorectal, non-neuroendocrine (NCRNNE) liver metastases. METHODS: One
      hundred and thirty-four patients undergoing curative liver resection for NCRNNE
      liver metastases were retrospectively analyzed. Perioperative results (blood
      transfusion, hospital stay, morbidity and mortality), 3 and 5-year overall and
      disease-free survival were evaluated. The following prognostic factors were
      analyzed: age (cut-off 50 year old), single vs. multiple nodules, diameter (cut
      off 5 cm), disease-free interval less vs. more than one year, type of primary
      tumor, blood transfusion, major hepatectomy vs. minor hepatectomy. Survival of
      patients undergoing liver resection for metastatic colorectal cancer was also
      analyzed to compare the results with the study population. RESULTS: Mortality and
      morbidity rate were 3% and 23.1%, respectively. The 3 and 5-year survival were
      56.5% and 40%, respectively. The 3 and 5-year disease-free survival were 44% and
      30%, respectively. Diameter, disease-free interval and metastases from
      gastrointestinal cancers were independently related to the survival at the
      multivariate analysis. Thirty-nine patients (27%) survived over five years.
      Patients with liver metastases from gastrointestinal primary tumors were those
      with a worse survival (25% and 19% at 3 and 5 years, respectively). CONCLUSIONS:
      Surgery is an effective treatment for patients with NCRNNE liver metastases,
      providing satisfactory long-term outcomes with acceptable morbidity and
      mortality, in particular when excluding patients with gastro-intestinal
      metastases.

PMID- 20029353
TI  - Use of alprostadil, a stable prostaglandin E1 analogue, for the attenuation of
      rat skeletal muscle ischemia and reperfusion injury.
AB  - AIM: Some stable prostaglandin analogues such as alprostadil have been used to
      attenuate the deleterious effects of ischemia and reperfusion injury. The aim of
      this paper was to test if alprostadil can decrease the ischemia- reperfusion
      injury in rat skeletal muscle using muscular enzymes as markers, such as
      aspartate aminotransferase (AST), creatine kinase (CPK), lactate dehydrogenase
      (LDH); degeneration products of cell membrane-malondialdehyde (MDA) and muscle
      glycogen storage. METHODS: Thirty male Wistar rats were used in a model of hind
      limb ischemia achieved by infrarenal aortic cross-clamping. The animals were
      randomized into three equal groups (N=10) submitted to 5 hours of ischemia
      followed by one hour of reperfusion. The first group (control) received
      continuous intravenous infusion of saline solution and the second group
      (preischemia, GPI) received continuous intravenous infusion of alprostadil
      throughout the experiment starting 20 minutes before the aortic cross-clamping.
      The third group, prereperfusion (GPR), received alprostadil only during the
      reperfusion period, with intravenous infusion being started 10 min before the
      clamp release. RESULTS: There was no difference in CPK, LDH, AST or tissue
      glycogen values between groups. However, a significant elevation in MDA was
      observed in the GPI and GPR groups compared to the control group, with no
      difference between the GPI and GPR. CONCLUSIONS: Under conditions of partial
      skeletal muscle ischemia, alprostadil did not reduce the release of muscular
      enzymes, the consumption of tissue glycogen or the effects of ischemia and
      reperfusion on the cell membrane, characterized by lipid peroxidation.

PMID- 20029355
TI  - Minimally invasive surgical techniques in the treatment of lung cancer.
AB  - Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer
      related mortality worldwide. Despite recent advances in molecular
      characterization, targeted and adjuvant therapies of NSCLC, surgical resection
      remains the mainstay of curative treatment. Minimally invasive video-assisted
      thoracic surgery (VATS) techniques, in particular VATS lobectomy, are being
      increasingly utilized over traditional thoracotomy approaches in the treatment of
      localized NSCLC for the reported benefits with respect to postoperative recovery
      and the conviction of oncologic equivalence. This article will review the major
      VATS procedures, including their development, outcomes, and purported advantages
      over thoracotomy, as well as highlight new advances, such as robotic-assisted
      procedures.

PMID- 20029354
TI  - Thyroidectomy in patients at high-risk of bleeding: can it be safely performed?
AB  - AIM: This study evaluated the safety of thyroid surgery in patients where
      anticoagulation was unavoidable or in patients with coagulopathy. METHODS: The
      records of all patients having high risk of bleeding at the time of thyroidectomy
      (July 2000 and March 2005) were retrospectively reviewed to evaluate
      intraoperative and postoperative bleeding. RESULTS: Ten patients were studied.
      Thyroid lobectomy with isthmusectomy (N=3) and bilateral thyroidectomy (N=7) were
      performed. Intraoperative surgical hemostasis was meticulous using ligasure
      vessel sealing system. Patients were divided in 3 groups. Group I (N=2) had small
      vessel vasculitis, underwent thyroidectomy under full heparinization. Heparin
      therapy was continued until full anticoagulation by oral anticoagulants. Group II
      (N=2) had a documented congenital coagulation defect, had a pre and postoperative
      special protocols. Group III (N=6) underwent simultaneous thyroid and cardiac
      surgery (e.g.: intraoperative full heparinization and postoperative antiplatelet
      therapy in some cases). No extra-bleeding was noted on surgical reports. In the
      postoperative period, one patient developed a superficial small hematoma in the
      neck that resolved spontaneously. Transient unilateral laryngeal nerve palsy and
      transient hypocalcemia were seen in one and two patients respectively.
      CONCLUSIONS: Thyroidectomy in patients with coagulopathy is feasible with low
      risk of bleeding if meticulous hemostasis, particularly using ligasure vessel
      sealing system, is respected.

PMID- 20029356
TI  - Stereotactic radiosurgery for lung cancer.
AB  - Lung cancer is the most common cause of cancer death in both men and women in the
      United States. Anatomic lobectomy is the standard treatment and offers the best
      results for curative treatment of early stage non-small cell lung cancer (NSCLC).
      With an aging population, a significant proportion of patients are not surgical
      candidates at the time of diagnosis. In medically inoperable patients, standard
      external beam radiation has been offered as treatment, with suboptimal results.
      Stereotactic radiosurgery (SRS), a term coined by Leksell describes an approach
      using multiple convergent beams, precise localization with a stereotactic
      coordinate system, and rigid immobilization. It provides precise delivery of
      beams from multiple collimated paths which maximizes radiation delivery to the
      tumor, and minimizes the exposure of normal tissue. Early results with SRS are
      very encouraging, and prospective trials are underway in our institution and
      others to evaluate its role in early stage NSCLC. In article we review the role
      of stereotactic radiosurgery for the treatment of lung cancer.

PMID- 20029357
TI  - Adjuvant therapy for lung cancer.
AB  - To improve outcome of patients with lung cancer, the leading cause of cancer
      mortality worldwide, a multidisciplinary approach is required. Only approximately
      30% of all lung cancer patients present with early stage disease (IA-IIIA). For
      non-small cell lung cancer (NSCLC) complete surgical resection is currently
      considered to be the optimal treatment, but high rates of recurrence even after
      complete resection require to investigate regimes of additional therapy. In the
      last years, evidence for adjuvant chemotherapy in stage II and III of NSCLC was
      shown, supported by large clinical trials and meta-analyses, while for stage IB
      disease the role of adjuvant chemotherapy remains controversial. Further there is
      actually no evidence to support the routine use of adjuvant radiation or radio
      chemotherapy in completely resected patients. For small cell lung cancer (SCLC) a
      multimodality adjuvant approach is feasible in early stages, his definitive value
      however should be evaluated in further randomized trials. Current efforts are
      directed toward identification of prognostic and predictive markers to
      individualize treatment stratification, a realistic goal for the future. The
      current status and future perspectives of adjuvant therapy in lung cancer are
      reviewed in this manuscript.

PMID- 20029358
TI  - Neoadjuvant chemotherapy for non-small cell lung cancer.
AB  - Even with aggressive surgical treatment, relapse rates remain high for patients
      with resectable non-small cell lung cancer (NSCLC). In an effort to improve
      survival in these patients, numerous clinical trials have evaluated neoadjuvant
      and adjuvant chemotherapy. Three large, randomized clinical trials and two meta
      analyses have demonstrated a survival benefit for adjuvant cisplatin-based
      chemotherapy compared to surgery alone. Adjuvant chemotherapy has become the
      standard of care for patients with resected NSCLC. A neoadjuvant approach offers
      several potential advantages over adjuvant therapy, including earlier treatment
      of micrometastatic disease, improved compliance and pathologic confirmation of
      efficacy. Randomized trials have shown neoadjuvant therapy to be feasible and
      safe and some studies have yielded promising efficacy. The applicability of these
      results has been limited due to patient heterogeneity, imprecise staging and lack
      of standardization with respect to inclusion of radiation therapy. With novel
      agents, improved staging, better supportive care and relevant molecular markers,
      a neoadjuvant strategy is promising for future clinical trials in NSCLC.

PMID- 20029359
TI  - Chemotherapy regimens for non-small cell lung cancer.
AB  - In spite of medical progresses, lung cancer still remains the leading cause of
      cancer-related deaths. Treatment of lung cancer is based on a multidisciplinary
      approach including surgery, chemotherapy, radiotherapy, molecular targeted
      therapies and supportive cares. These different treatments have been largely
      evaluated in the last decades with an enormous quantity of available literature.
      In this paper, authors provide a short review on chemotherapy in non-small cell
      lung cancer, based on a selection of the most relevant trials. The use in
      different settings is reviewed, including adjuvant and neo-adjuvant treatments in
      operable patients as well as therapy in inoperable patients. The association with
      both radiotherapy and recently available molecular targeted therapies is also
      reviewed. In the adjuvant setting, chemotherapy achieved an approximately 5%
      increase in five-year survival, suggesting that studies to identify ideal
      candidates to this combined treatment are mandatory. In inoperable patients, the
      efficacy of chemotherapy has been definitively established, as it provides a
      significant survival advantage, with improved quality of life, over best
      supportive cares. Evidences exist on the benefit of the association of molecular
      targeted drugs to chemotherapy. However, more trials comparing combinations of
      chemotherapy, radiotherapy, biological therapies, at different doses and
      duration, are needed. Further research on toxicity and costs are also needed. The
      possibility of choosing the most appropriate cancer treatment on an individual
      basis represents the main challenge for the future.

PMID- 20029360
TI  - Cancer vaccines for non-small-cell lung cancer.
AB  - Lung cancer is globally the second most common form of cancer in both men and
      women and the single largest cause of cancer-related mortality in the world. It
      is a disease with poor prognosis and the survival statistics have scarcely
      improved since historical times. The advent of targeted therapies has caused an
      incremental increase in survival figures. Nevertheless, significant progress in
      treatment outcomes need to be achieved before any perceptible improvement in
      overall survival of lung cancer patients becomes evident. The use of active
      specific immunotherapy or cancer vaccines for the treatment of lung cancer is
      still in its infancy. Nevertheless several cancer vaccines have demonstrated
      clinical effects and improvements in overall survival in phase II and phase III
      trials and several more clinical trials are currently ongoing. This review
      summarizes the recent developments in NSCLC vaccines.

PMID- 20029361
TI  - Quality of life after lung cancer surgery: a review.
AB  - The long-term goals of lung cancer surgery include cancer control, survival and
      quality of life (QoL). In a patient population with a high mortality rate,
      evaluation and preservation of QoL after treatment is imperative. Lung cancer
      patients already have a significant lower QoL compared to an age-matched healthy
      population with significant impairment in physical and emotional functioning.
      Lung cancer surgery causes further deterioration of QoL, especially in the first
      3 to 6 months after surgery. While some studies suggest that QOL returns to
      baseline levels at 6 to 9 months postoperatively, others report that QOL is still
      significantly impaired at 6 and 12 months after surgery. Age, extent of surgery,
      preoperative lung function, access technique, and adjuvant treatment may all
      influence postoperative QoL. This review presents the basic concepts of QoL
      research, several commonly used QoL measurement instruments, and a summary of the
      available data on post-lung cancer surgery QoL.

PMID- 20029362
TI  - Resection and end-to-end anastomosis for ascending aortic aneurysm: surgical
      technique.
AB  - Treatment of ascending aortic aneurysm, without involvement of aortic sinuses of
      Valsalva, is usually treated by tube graft interposition. Nowadays, many
      alternative techniques were described. The technique of resection and end-to-end
      anastomosis has been already described both by our group and by other authors as
      well. This report will focus on some surgical details of this technique based on
      a ten-year-experience. The preoperative study of candidates amenable to undergo
      this technique has to be completed by a computed tomography-scan of thoracic
      aorta. The ideal candidate has an elongated aorta in the antero-lateral wall. As
      a consequence, the heart is usually displaced inferiorly and toward a more
      horizontal plane. The aortotomy is done circumferentially one and half cm above
      the aortic commissures. A wide wedge resection of the aortic wall is performed.
      The resected aortic wall is wider in the anterior part than in the posterior. A
      very accurate hemostasis of the fat tissue close to the pulmonary artery is
      achieved by diathermy. The amount of wedge resection is mainly dictated by the
      elongation of the aortic wall. In authors' experience it usually ranges between 4
      and 6 cm anteriorly and 1 cm posteriorly. The suture of the two stumps is
      performed by a running suture. The technique described has extensively been used;
      up today 136 patients undergo. According to authors' opinion this technique can
      be a useful alternative to the tube graft interposition in selected patients.

PMID- 20029363
TI  - Synchronous pleuro - renal solitary fibrous tumors: a new clinical-pathological
      finding.
AB  - Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal neoplasms
      usually originating from the visceral pleura, but sometimes found in other sites
      like the orbit, dura, paranasal sinus, upper respiratory tract, thyroid,
      sublingual gland, lung, periosteum, cauda equina, ovary, scrotum and testicular
      tunica vaginalis. Solitary fibrous tumor of the kidney is extremely rare with
      fewer than 15 reported cases in modern English literature. To the best of our
      knowledge, this report describes the first known case of synchronous SFTP in the
      left parietal pleura and left kidney. The SFTP of the pleura, widely compressing
      and displacing the left lower lung lobe, was resected via left thoracotomy,
      whereas the renal SFTP, diagnosed by echo-guided histological biopsy, was closely
      monitored by computed tomography scan and ultrasound. After a one-year follow-up
      no recurrence was detected in the left hemithorax and the renal lesion remained
      stable.

PMID- 20029364
TI  - Isolated dissection of the superior mesenteric artery: conservative approach in a
      selected patient.
AB  - The authors present the case report of effective conservative treatment in a
      patient with spontaneous, self-limiting, non-atherosclerotic dissection of the
      superior mesenteric artery (SMA) without fixed obstruction of the vessel lumen
      and signs of intestinal ischemia. Treatment with both anti-coagulant and anti
      hypertensive agents succeeded in limiting the progression of intimal dissection
      and in preventing the potential dramatic sequelae of this rare clinical
      condition. Conservative treatment of spontaneous SMA dissection may be an
      alternative to surgery, if residual blood flow is maintained.

PMID- 20029367
TI  - Culture and maintenance of human embryonic stem cells.
AB  - Human embryonic stem (hES) cells must be monitored and cared for in order to
      maintain healthy, undifferentiated cultures. At minimum, the cultures must be fed
      every day by performing a complete medium change to replenish lost nutrients and
      to keep the cultures free of unwanted differentiation factors. Although a small
      amount of differentiation is normal and expected in stem cell cultures, the
      culture should be routinely cleaned up by manually removing, or "picking"
      differentiated areas. Identifying and removing excess differentiation from hES
      cell cultures are essential techniques in the maintenance of a healthy population
      of cells.

PMID- 20029368
TI  - Theoretical and experimental analysis links isoform-specific ERK signalling to
      cell fate decisions.
AB  - Cell fate decisions are regulated by the coordinated activation of signalling
      pathways such as the extracellular signal-regulated kinase (ERK) cascade, but
      contributions of individual kinase isoforms are mostly unknown. By combining
      quantitative data from erythropoietin-induced pathway activation in primary
      erythroid progenitor (colony-forming unit erythroid stage, CFU-E) cells with
      mathematical modelling, we predicted and experimentally confirmed a distributive
      ERK phosphorylation mechanism in CFU-E cells. Model analysis showed bow-tie
      shaped signal processing and inherently transient signalling for cytokine-induced
      ERK signalling. Sensitivity analysis predicted that, through a feedback-mediated
      process, increasing one ERK isoform reduces activation of the other isoform,
      which was verified by protein over-expression. We calculated ERK activation for
      biochemically not addressable but physiologically relevant ligand concentrations
      showing that double-phosphorylated ERK1 attenuates proliferation beyond a certain
      activation level, whereas activated ERK2 enhances proliferation with saturation
      kinetics. Thus, we provide a quantitative link between earlier unobservable
      signalling dynamics and cell fate decisions.

PMID- 20029369
TI  - Update on the Keio collection of Escherichia coli single-gene deletion mutants.

PMID- 20029370
TI  - A global view of protein expression in human cells, tissues, and organs.
AB  - Defining the protein profiles of tissues and organs is critical to understanding
      the unique characteristics of the various cell types in the human body. In this
      study, we report on an anatomically comprehensive analysis of 4842 protein
      profiles in 48 human tissues and 45 human cell lines. A detailed analysis of over
      2 million manually annotated, high-resolution, immunohistochemistry-based images
      showed a high fraction (>65%) of expressed proteins in most cells and tissues,
      with very few proteins (<2%) detected in any single cell type. Similarly,
      confocal microscopy in three human cell lines detected expression of more than
      70% of the analyzed proteins. Despite this ubiquitous expression, hierarchical
      clustering analysis, based on global protein expression patterns, shows that the
      analyzed cells can be still subdivided into groups according to the current
      concepts of histology and cellular differentiation. This study suggests that
      tissue specificity is achieved by precise regulation of protein levels in space
      and time, and that different tissues in the body acquire their unique
      characteristics by controlling not which proteins are expressed but how much of
      each is produced.

PMID- 20029371
TI  - Chemogenomic profiling predicts antifungal synergies.
AB  - Chemotherapies, HIV infections, and treatments to block organ transplant
      rejection are creating a population of immunocompromised individuals at serious
      risk of systemic fungal infections. Since single-agent therapies are susceptible
      to failure due to either inherent or acquired resistance, alternative therapeutic
      approaches such as multi-agent therapies are needed. We have developed a
      bioinformatics-driven approach that efficiently predicts compound synergy for
      such combinatorial therapies. The approach uses chemogenomic profiles in order to
      identify compound profiles that have a statistically significant degree of
      similarity to a fluconazole profile. The compounds identified were then
      experimentally verified to be synergistic with fluconazole and with each other,
      in both Saccharomyces cerevisiae and the fungal pathogen Candida albicans. Our
      method is therefore capable of accurately predicting compound synergy to aid the
      development of combinatorial antifungal therapies.

PMID- 20029372
TI  - Desaturation of excess intramyocellular triacylglycerol in obesity: implications
      for glycemic control.
AB  - OBJECTIVE: Excess intramyocellular triacylglycerol (IMTG), found especially in
      obese women, is slowly metabolized and, therefore, prone to longer exposure to
      intracellular desaturases. Accordingly, it was hypothesized that IMTG content
      correlates inversely with IMTG fatty acid (FA) saturation in sedentary subjects.
      In addition, it was validated if IMTG palmitic acid is associated with insulin
      resistance as suggested earlier. DESIGN: Cross-sectional human study. SUBJECTS:
      In skeletal muscle biopsies, which were obtained from sedentary subjects (34
      women, age 48+/-2 years (27 obese including 7 type 2 diabetes (T2DM), body mass
      index (BMI)=35.5+/-0.8 kg m(-2)) and 25 men, age 49+/-2 years (20 obese including
      6 T2DM, BMI=35.8+/-0.8 kg m(-2))), IMTG FA composition was determined by gas
      liquid chromatography after separation from phospholipids by thin-layer
      chromatography. RESULTS: Independently of gender saturated FA correlated
      inversely with IMTG (P<0.001) and monounsaturated FA (P<0.001) including total
      unsaturation of FA (P<0.002) correlated positively with IMTG. Obese women
      exhibited lower total saturated FA (P<0.001) and palmitic acid (P<0.001) than
      obese men independent of IMTG, the latter of which, however, was increased
      twofold in obese women compared to obese men (P<0.001). Polyunsaturated and long
      chain polyunsaturated FA did not correlate with IMTG. Palmitic acid correlated
      positively with insulin resistance (homeostasis insulin resistance index,
      P<0.05), fasting glucose (P<0.01) and glycosylated hemoglobin (P<0.002) both in
      univariate analysis and after correction for gender and IMTG. CONCLUSION: IMTG
      content correlates inversely with IMTG saturated FA, potentially reflecting a low
      turnover of excess IMTG prone to in situ desaturation probably by the ubiquitous
      stearoyl-CoA desaturase-1. IMTG FA composition is gender specific and implicates
      on insulin sensitivity and glycemic control.

PMID- 20029373
TI  - A nationally representative study of maternal obesity in England, UK: trends in
      incidence and demographic inequalities in 619 323 births, 1989-2007.
AB  - BACKGROUND: There is an absence of national statistics for maternal obesity in
      the UK. This study is the first to describe a nationally representative maternal
      obesity research data set in England. DESIGN: Retrospective epidemiological study
      of first trimester obesity. METHODS: Data from 34 maternity units were analysed,
      including 619 323 births between 1989 and 2007. Data analysis included trends in
      first trimester maternal body bass index status over time, and geographical
      distribution of maternal obesity. Population demographics including maternal age,
      parity, ethnic group, deprivation and employment were analysed to identify any
      maternal obesity-associated health inequalities. All demographics were tested for
      multicollinearity. Logistic regression analyses were adjusted for all
      demographics as confounders. RESULTS: First trimester maternal obesity is
      significantly increasing over time, having more than doubled from 7.6% to 15.6%
      over 19 years (P<0.001), and shows geographic variation in incidence. There are
      also demographic health inequalities associated with maternal obesity, including
      increased odds of being obese with increasing age, parity, Black ethnic group and
      deprivation. There is also an association between morbid obesity and increased
      levels of unemployment. CONCLUSIONS: The increase in maternal obesity has serious
      implications for the health of mothers, infants and service providers, yielding
      an additional 47 500 women per year requiring high dependency care in England.
      The demography of women most at risk of first trimester obesity highlights health
      inequalities associated with maternal obesity, which urgently needs to be
      addressed.

PMID- 20029374
TI  - Thyroid hormone responsive Spot 14 increases during differentiation of human
      adipocytes and its expression is down-regulated in obese subjects.
AB  - CONTEXT: Very limited information is available regarding the function of human
      thyroid hormone responsive Spot 14 (human S14, hS14) in adipogenesis and human
      adiposity. OBJECTIVE: To evaluate hS14 levels during differentiation of human pre
      adipocytes, in human fat depots and isolated fat cells. DESIGN: This was a cross
      sectional study. SUBJECTS: A total of 161 omental (OM) and 87 subcutaneous (SC)
      adipose tissue samples obtained during elective surgical procedures from a
      population who varied widely in terms of obesity. MEASUREMENTS: hS14 gene
      expression and protein levels during adipogenesis were assessed by RT-PCR,
      western blot, and using an automated confocal imaging approach. RESULTS: hS14
      gene expression levels were decreased in OM adipose tissue from overweight (
      42.0%) and obese subjects (-56.5%) compared with lean subjects (P<0.05 and
      P<0.0001, respectively). hS14 mRNA (but not hS14-related) was inversely
      associated with obesity measures such as body mass index (P=0.001), percent fat
      mass (P=0.001), waist-to-hip ratio (P=0.020), and systolic blood pressure
      (P=0.031). hS14 gene expression and protein levels were up-regulated at the early
      stages of differentiation of human pre-adipocytes as well as for 3T3-L1 cells.
      That observation was most prominent in those individual cells exhibiting the more
      marked differentiation features. hS14 gene expression levels increased by
      approximately 45 000-fold in mature adipocytes. Increased hS14 levels were also
      found in stromal-vascular cells/pre-adipocytes (3.8-fold, P<0.05) and in adipose
      tissue samples (1.9-fold, P<0.0001) from SC compared with OM fat depots.
      CONCLUSIONS: These results suggest that hS14 is involved in human adipogenesis,
      but inversely related to obesity and OM fat accumulation.

PMID- 20029375
TI  - FAAH deficiency promotes energy storage and enhances the motivation for food.
AB  - RATIONALE: Fatty acid amide hydrolase (FAAH) is the main degrading enzyme of the
      fatty acid ethanolamides anandamide (AEA) and oleoylethanolamide (OEA), which
      have opposite effects on food intake and energy balance. AEA, an endogenous
      ligand of CB(1) cannabinoid receptors, enhances food intake and energy storage,
      whereas OEA binds to peroxisome proliferator-activated receptors-alpha to reduce
      food intake and promoting lipolysis. To elucidate the role of FAAH in food intake
      and energy balance, we have evaluated different metabolic and behavioral
      responses related to feeding in FAAH-deficient (FAAH(-/-)) mice and their wild
      type littermates. METHODOLOGY AND RESULTS: Total daily food intake was similar in
      both genotypes, but high-fat food consumption was enhanced during the dark hours
      and decreased during the light hours in FAAH(-/-) mice. The reinforcing and
      motivational effects of food were also enhanced in FAAH(-/-) mice as revealed by
      operant behavioral paradigms. These behavioral responses were reversed by the
      administration of the selective CB(1) cannabinoid antagonist rimonabant.
      Furthermore, body weight, total amount of adipose tissue, plasma-free fatty acids
      and triglyceride content in plasma, liver, skeletal muscle and adipose tissue,
      were increased in FAAH(-/-) mice. Accordingly, leptin levels were increased and
      adiponectin levels decreased in these mutants, FAAH(-/-) mice also showed
      enhanced plasma insulin and blood glucose levels revealing an insulin resistance.
      As expected, both AEA and OEA levels were increased in hypothalamus, small
      intestine and liver of FAAH(-/-) mice. CONCLUSION: These results indicate that
      the lack of FAAH predominantly promotes energy storage by food intake-independent
      mechanisms, through the enhancement of AEA levels rather than promoting the
      anorexic effects of OEA.

PMID- 20029376
TI  - The Ski proto-oncogene regulates body composition and suppresses lipogenesis.
AB  - OBJECTIVE: The Ski gene regulates skeletal muscle differentiation in vitro and
      and in vivo. In the c-Ski overexpression mouse model there occurs marked skeletal
      muscle hypertrophy with decreased adipose tissue mass. In this study, we have
      investigated the underlying molecular mechanisms responsible for the increased
      skeletal muscle and decreased adipose tissue mass in the c-Ski mouse. APPROACH:
      Growth and body composition analysis (tissue weights and dual energy X-ray
      absorptiometry) coupled with skeletal muscle and white adipose gene expression
      and metabolic phenotyping in c-Ski mice and wild-type (WT) littermate controls
      was performed. RESULTS: The growth and body composition studies confirmed the
      early onset of accelerated body growth, with increased lean mass and decreased
      fat mass in the c-Ski mice. Gene expression analysis in skeletal muscle from c
      Ski mice compared with WT mice showed significant differences in myogenic and
      lipogenic gene expressions that are consistent with the body composition
      phenotype. Skeletal muscle of c-Ski mice had significantly repressed Smad1, 4, 7
      and myostatin gene expression and elevated myogenin, myocyte enhancer factor 2,
      insulin-like growth factor-1 receptor and insulin-like growth factor-2
      expression. Strikingly, expression of the mRNAs encoding the master lipogenic
      regulators, sterol-regulatory enhancer binding protein 1c (SREBP1c), and the
      nuclear receptor liver X-receptor-alpha, and their downstream target genes, SCD-1
      and FAS, were suppressed in skeletal muscle of c-Ski mice, as were the
      expressions of other nuclear receptors involved in adipogenesis and metabolism,
      such as peroxisome proliferator-activated receptor-gamma, glucocorticoid receptor
      and retinoic acid receptor-related orphan receptor-alpha. Transfection analysis
      demonstrated Ski repressed the SREBP1c promoter. Moreover, palmitate oxidation
      and oxidative enzyme activity was increased in skeletal muscle of c-Ski mice.
      These results suggest that the Ski phenotype involves attenuated lipogenesis,
      decreased myostatin signalling, coupled to increased myogenesis and fatty acid
      oxidation. CONCLUSION: Ski regulates several genetic programs and signalling
      pathways that regulate skeletal muscle and adipose mass to influence body
      composition development, suggesting that Ski may have a role in risk for obesity
      and metabolic disease.

PMID- 20029377
TI  - Excessive fructose intake induces the features of metabolic syndrome in healthy
      adult men: role of uric acid in the hypertensive response.
AB  - BACKGROUND: Excessive fructose intake causes metabolic syndrome in animals and
      can be partially prevented by lowering the uric acid level. We tested the
      hypothesis that fructose might induce features of metabolic syndrome in adult men
      and whether this is protected by allopurinol. METHODS: A randomized, controlled
      trial of 74 adult men who were administered 200 g fructose daily for 2 weeks with
      or without allopurinol. Primary measures included changes in ambulatory blood
      pressure (BP), fasting lipids, glucose and insulin, homeostatic model assessment
      (HOMA) index, body mass index and criteria for metabolic syndrome. RESULTS: The
      ingestion of fructose resulted in an increase in ambulatory BP (7+/-2 and 5+/-2
      mm Hg for systolic (SBP) and diastolic BP (DBP), P<0.004 and P<0.007,
      respectively). Mean fasting triglycerides increased by 0.62+/-0.23 mmol l(-1)
      (55+/-20 mg per 100 ml), whereas high-density lipoprotein cholesterol decreased
      by 0.06+/-0.02 mmol l(-1) (2.5+/-0.7 mg per 100 ml), P<0.002 and P<0.001,
      respectively. Fasting insulin and HOMA indices increased significantly, whereas
      plasma glucose level did not change. All liver function tests showed an increase
      in values. The metabolic syndrome increased by 25-33% depending on the criteria.
      Allopurinol lowered the serum uric acid level (P<0.0001) and prevented the
      increase in 24-h ambulatory DBP and daytime SBP and DBP. Allopurinol treatment
      did not reduce HOMA or fasting plasma triglyceride levels, but lowered low
      density lipoprotein cholesterol relative to control (P<0.02) and also prevented
      the increase in newly diagnosed metabolic syndrome (0-2%, P=0.009). CONCLUSIONS:
      High doses of fructose raise the BP and cause the features of metabolic syndrome.
      Lowering the uric acid level prevents the increase in mean arterial blood
      pressure. Excessive intake of fructose may have a role in the current epidemics
      of obesity and diabetes.

PMID- 20029378
TI  - Tackling the growth of the obesity literature: obesity evidence spreads across
      many journals.
AB  - OBJECTIVE: This study identified the journals with the highest yield of clinical
      obesity research articles and surveyed the scatter of such studies across
      journals. The study exemplifies an approach to establish a journal collection
      that is likely to contain most new knowledge about a field. DESIGN AND METHODS:
      All original studies that were cited in 40 systematic reviews about obesity
      topics ('included studies') were compiled and journal titles in which they were
      published were extracted. The journals were ranked by the number of included
      studies. The highest-yielding journals for clinical obesity and the scatter
      across journal titles were determined. A subset of these journals was created in
      MEDLINE (PubMed) to test search recall and precision for high-quality studies of
      obesity treatment (that is, articles that pass predetermined methodology
      criteria, including random allocation of participants to comparison groups,
      assessment of clinical outcomes, and at least 80% follow-up). RESULTS: Articles
      in 252 journals were cited in the systematic reviews. The three highest-yielding
      journals specialized in obesity, but they published only 19.2% of the research,
      leaving 80.8% scattered across 249 non-obesity journals. The MEDLINE journal
      subset comprised 241 journals (11 journals were not indexed in MEDLINE) and
      included 82% of the clinical obesity research articles retrieved by a search for
      high-quality treatment studies ('recall' of 82%). Of the articles retrieved, 11%
      were about clinical obesity care ('precision' of 11%), compared with precision of
      6% for obesity treatment studies in the full MEDLINE database. CONCLUSION:
      Obesity journals captured only a small proportion of the literature on clinical
      obesity care. Those wishing to keep up in this field will need to develop more
      inclusive strategies than reading these specialty journals. A journal subset
      based on these findings may be useful when searching large electronic databases
      to increase search precision.

PMID- 20029379
TI  - Peripherally acting CB1-receptor antagonist: the relative importance of central
      and peripheral CB1 receptors in adiposity control.
AB  - OBJECTIVE: To investigate whether drugs targeting peripheral cannabinoid-1 (CB1)
      receptor ameliorate adiposity comparable to central CB1-receptor antagonist or
      not. MEASUREMENTS: Receptor binding assay and functional assay in vitro.
      Pharmacokinetic parameters in mice, brain uptake clearance of compounds in rats
      and antagonism on the CB1-agonist-induced hypothermia in mice. Diet consumption,
      body weight changes, hepatic gene expression of sterol-regulatory element-binding
      protein-1 (SREBP-1) and plasma/tissue concentrations of compounds in HF diet
      induced obese (HF-DIO) mice after acute and chronic treatment. RESULTS: Compound
      1, an SR141716A derivative, is a peripheral CB1-receptor-selective antagonist
      that is 10 times less potent than SR141716A in in vitro evaluations. Although the
      plasma concentrations of Compound-1 are five times higher than those of
      SR141716A, its potency is still 10 times lower than that of SR141716A in reducing
      the consumption of normal or HF diet by mice. Through evaluations of brain uptake
      and the effect on CB1-agonist-induced hypothermia, it was verified that the blood
      brain barrier (BBB) penetration of Compound-1 is much lower than that of
      SR141716A. In HF-DIO mice, chronic treatment by Compound-1 showed dose-dependent
      antiobesity activities, while its brain distribution was very low as compared
      with that of SR141716A. Compound-1's effective doses for antiobesity activity
      were just over 30 mg kg(-1). However, Compound-1 completely suppressed the
      elevated hepatic SREBP-1 expression even at 10 mg kg(-1). CONCLUSION: These
      results suggest that (1) central CB1 receptors mediate anorectic response of CB1
      receptor antagonists and (2) peripheral modulations, including SREBP-1
      expression, are not major mechanisms in the antiobesity effects of CB1-receptor
      antagonists.

PMID- 20029380
TI  - Insufficient evidence to support separate BMI definitions for obesity in children
      and adolescents from south Asian ethnic groups in the UK.
AB  - Re-evaluation of adult obesity thresholds in some ethnic groups has led to the
      questioning of childhood obesity thresholds. An expert group was convened to
      examine the representativeness of childhood obesity definitions, evidence for
      ethnic differences in body composition in UK children and the extent of
      misclassification of adiposity by current body mass index (BMI) thresholds in
      south Asian and black groups. The group concluded that the current International
      Obesity Task Force (IOTF) definitions remained the most appropriate for use in
      the United Kingdom, but further research was needed on the relationship of body
      shape, fat mass, metabolic markers and ethnicity in children and adolescents.

PMID- 20029381
TI  - Blood orange juice inhibits fat accumulation in mice.
AB  - OBJECTIVE: To analyze the effect of the juice obtained from two varieties of
      sweet orange (Citrus sinensis L. Osbeck), Moro (a blood orange) and Navelina (a
      blond orange), on fat accumulation in mice fed a standard or a high-fat diet
      (HFD). METHODS: Obesity was induced in male C57/Bl6 mice by feeding a HFD. Moro
      and Navelina juices were provided instead of water. The effect of an anthocyanin
      enriched extract from Moro oranges or purified cyanidin-3-glucoside (C3G) was
      also analyzed. Body weight and food intake were measured regularly over a 12-week
      period. The adipose pads were weighted and analyzed histologically; total RNA was
      also isolated for microarray analysis. RESULTS: Dietary supplementation of Moro
      juice, but not Navelina juice significantly reduced body weight gain and fat
      accumulation regardless of the increased energy intake because of sugar content.
      Furthermore, mice drinking Moro juice were resistant to HFD-induced obesity with
      no alterations in food intake. Only the anthocyanin extract, but not the purified
      C3G, slightly affected fat accumulation. High-throughput gene expression analysis
      of fat tissues confirmed that Moro juice could entirely rescue the high fat
      induced transcriptional reprogramming. CONCLUSION: Moro juice anti-obesity effect
      on fat accumulation cannot be explained only by its anthocyanin content. Our
      findings suggest that multiple components present in the Moro orange juice might
      act synergistically to inhibit fat accumulation.

PMID- 20029382
TI  - A free-choice high-fat high-sugar diet induces changes in arcuate neuropeptide
      expression that support hyperphagia.
AB  - OBJECTIVES: The mechanisms for how saturated fat and sugar-based beverages
      contribute to human obesity are poorly understood. This paper describes a series
      of experiments developed to examine the response of hypothalamic neuropeptides to
      diets rich in sugar and fat, using three different diets: a high-fat high-sugar
      (HFHS) choice diet with access to chow, saturated fat and a 30% sugar solution; a
      high-fat (HF) choice diet with access to chow and saturated fat; or to a high
      sugar (HS) choice diet with access to chow and a sugar solution. METHOD: We first
      studied caloric intake, body weight gain, hormonal alterations and hypothalamic
      neuropeptide expression when male Wistar rats were subjected to an HFHS choice,
      an HF choice or an HS choice diet for 1 week. Next, we studied caloric intake and
      body weight gain when rats were subjected to the choice diets for 5 weeks.
      Finally, we measured neuropeptide expression in hepatic vagotomized rats
      subjected to an HFHS choice, an HF choice or an HS choice diet for 1 week.
      RESULTS: In rats on an HF choice diet, plasma leptin concentrations and
      proopiomelanocortin (POMC) mRNA increased and neuropeptide Y (NPY) mRNA
      decreased. Rats on an HFHS choice diet showed identical plasma leptin
      concentrations as rats on an HF choice diet. However, NPY mRNA increased and POMC
      mRNA decreased. An HS choice diet for 1 week did not alter hypothalamic
      neuropeptide expression or plasma leptin concentrations. As hormonal changes did
      not explain the differences in hypothalamic neuropeptide expression between rats
      on the choice diets, we addressed whether neuronal feedback signals mediated the
      hypothalamic neuropeptide response. The POMC mRNA response to different diets
      depended on an intact innervation of liver and upper intestinal tract.
      CONCLUSION: Our data suggest that the specific combination of saturated fat and a
      30% sugar solution results in hyperphagia-induced obesity and alters hypothalamic
      neuropeptide expression, and that the response of the melanocortin system is
      mediated by the hepatic vagus.

PMID- 20029383
TI  - Acute effects of gastric bypass versus gastric restrictive surgery on beta-cell
      function and insulinotropic hormones in severely obese patients with type 2
      diabetes.
AB  - CONTEXT: Hyperglycemia resolves quickly after bariatric surgery, but the
      underlying mechanism and the most effective type of surgery remains unclear.
      OBJECTIVE: To examine glucose metabolism and beta-cell function in patients with
      type 2 diabetes mellitus (T2DM) after two types of bariatric intervention; Roux
      en-Y gastric bypass (RYGB) and gastric restrictive (GR) surgery. DESIGN:
      Prospective, nonrandomized, repeated-measures, 4-week, longitudinal clinical
      trial. PATIENTS: In all, 16 T2DM patients (9 males and 7 females, 52+/-14 years,
      47+/-9 kg m(-2), HbA1c 7.2+/-1.1%) undergoing either RYGB (N=9) or GR (N=7)
      surgery. OUTCOME MEASURES: Glucose, insulin secretion, insulin sensitivity at
      baseline, and 1 and 4 weeks post-surgery, using hyperglycemic clamps and C
      peptide modeling kinetics; glucose, insulin secretion and gut-peptide responses
      to mixed meal tolerance test (MMTT) at baseline and 4 weeks post-surgery.
      RESULTS: At 1 week post-surgery, both groups experienced a similar weight loss
      and reduction in fasting glucose (P<0.01). However, insulin sensitivity increased
      only after RYGB, (P<0.05). At 4 weeks post-surgery, weight loss remained similar
      for both groups, but fasting glucose was normalized only after RYGB (95+/-3 mg
      100 ml(-1)). Insulin sensitivity improved after RYGB (P<0.01) and did not change
      with GR, whereas the disposition index remained unchanged after RYGB and
      increased 30% after GR (P=0.10). The MMTT elicited a robust increase in insulin
      secretion, glucagon-like peptide-1 (GLP-1) levels and beta-cell sensitivity to
      glucose only after RYGB (P<0.05). CONCLUSION: RYGB provides a more rapid
      improvement in glucose regulation compared with GR. This improvement is
      accompanied by enhanced insulin sensitivity and beta-cell responsiveness to
      glucose, in part because of an incretin effect.

PMID- 20029384
TI  - Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment
      response: exploratory analysis of nine polymorphisms and meta-analysis of the
      Ser9Gly variant.
AB  - D2 blockade has been implicated in having a central role in antipsychotic
      response. However, treatment refractoriness, in spite of complete D2 blockade, as
      well as the efficacy of clozapine (CLZ) in a portion of this patient population,
      indicates the involvement of other factors as well. Several lines of evidence
      suggest a role for D3. Furthermore, an earlier meta-analysis by Jonsson et al.
      (2003) (n=233) suggested a role for genetic variation in the D3 gene. Relevant to
      this study, Jonsson et al. found the Ser allele of the D3 serine-to-glycine
      substitution at amino acid position 9 (Ser9Gly) polymorphism to be associated
      with worse CLZ response compared with the Gly allele. In this study, we attempt
      to validate these findings by performing a meta-analysis in a much larger sample
      (n=758). Eight other variants were also tested in our own sample to explore the
      possible effect of other regions of the gene. We report a negative but consistent
      trend across individual studies in our meta-analysis for the DRD3 Ser allele and
      poor CLZ response. A possible minor role for this single-nucleotide polymorphism
      cannot be disregarded, as our sample size may have been insufficient. Other DRD3
      variants and haplotypes of possible interest were also identified for replication
      in future studies.

PMID- 20029385
TI  - Weight gain related to treatment with atypical antipsychotics is due to
      activation of PKC-beta.
AB  - Atypical antipsychotics (APDs) are currently used in clinical practice for a
      variety of mental disorders such as schizophrenia, bipolar disorder and severe
      behavioral disturbances. A well-known disadvantage of using these compounds is a
      propensity for weight gain, resulting frequently in obesity. The mechanisms
      underlying pharmacologically induced weight gain are still controversial. The
      objective of this study was to evaluate in vitro the effects of different APDs on
      adipogenic events in cultured human pre-adipocytes and in rat muscle-derived stem
      cells (MDSCs), aiming to identify a common intracellular event contributable to
      these drugs. Culture behavior was evaluated in terms of cell proliferation, lipid
      accumulation, gene expression and morphological features. Results indicate that
      APDs influence adipogenic events through changes in the differentiation and
      proliferation of pre-adipocytes and MDSCs that are brought on by protein kinase C
      beta (PKC-beta) activation. These data identify a signaling route that could be a
      potential target of pharmacological approaches for preventing the weight gain
      associated with APD treatment.

PMID- 20029387
TI  - Functional analysis of intron 8 and 3' UTR variable number of tandem repeats of
      SLC6A3: differential activity of intron 8 variants.
AB  - Association studies have found that variation in the dopamine transporter gene
      (SLC6A3) is important in the susceptibility to attention-deficit hyperactivity
      disorder (ADHD) and response to methylphenidate treatment. An understanding of
      the biological mechanisms underlying these associations is still inconclusive. We
      assessed the relative activity of variable number tandem repeat (VNTR) alleles of
      SLC6A3 under basal and stimulated cellular conditions, as well as in the presence
      of pharmacological blockade of the dopamine transporter using gene-reporter
      constructs. The intron 8 VNTR 5-repeat allele is more active than the 6-repeat
      allele. In the presence of forskolin, both alleles were significantly induced.
      Blockade of the dopamine transporter did not influence activity of either allelic
      construct. No difference in activity between 9- and 10-repeat alleles of the 3'
      untranslated region VNTR was observed under any experimental condition. These
      data suggest that the intron 8 VNTR is a functional variant with an ADHD
      susceptibility allele having reduced activity. The lack of enhanced allele
      specific activity in response to treatment regimes suggests that differential
      activity under basal conditions is the primary mode of action.

PMID- 20029386
TI  - A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's
      disease.
AB  - The E4 allele of the apolipoprotein E (APOE) gene is currently the strongest and
      most highly replicated genetic factor for risk and age of onset of late-onset
      Alzheimer's disease (LOAD). Using phylogenetic analysis, we have identified a
      polymorphic poly-T variant, rs10524523, in the translocase of outer mitochondrial
      membrane 40 homolog (TOMM40) gene that provides greatly increased precision in
      the estimation of age of LOAD onset for APOE E3 carriers. In two independent
      clinical cohorts, longer lengths of rs10524523 are associated with a higher risk
      for LOAD. For APOE E3/4 patients who developed LOAD after 60 years of age,
      individuals with long poly-T repeats linked to APOE E3 develop LOAD on an average
      of 7 years earlier than individuals with shorter poly-T repeats linked to APOE E3
      (70.5 +/- 1.2 years versus 77.6 +/- 2.1 years, P=0.02, n=34). Independent
      mutation events at rs10524523 that occurred during Caucasian evolution have given
      rise to multiple categories of poly-T length variants at this locus. On
      replication, these results will have clinical utility for predictive risk
      estimates for LOAD and for enabling clinical disease prevention studies. In
      addition, these results show the effective use of a phylogenetic approach for
      analysis of haplotypes of polymorphisms, including structural polymorphisms,
      which contribute to complex diseases.

PMID- 20029388
TI  - Evidence for the involvement of ActA in maturation of the Listeria monocytogenes
      phagosome.

PMID- 20029389
TI  - The serine/threonine kinase LKB1 controls thymocyte survival through regulation
      of AMPK activation and Bcl-XL expression.
AB  - LKB1 is a serine/threonine kinase that directly activates the energy sensor AMP
      activated protein kinase (AMPK) in response to bioenergetic stress, and mainly
      acts as a tumor suppressor that controls cell polarity and proliferation.
      Although LKB1 is expressed in multiple tissues including the thymus and the
      spleen, its roles in T-cell development and function remain unknown. Here, we
      show that T-cell-specific deletion of LKB1 resulted in reduced survival of double
      positive (DP) thymocytes and impaired generation of both CD4 and CD8 single
      positive thymocytes. Disruption of LKB1 not only prevented the activation of AMPK
      but also impaired the expression of anti-apoptotic protein Bcl-XL. Importantly,
      ectopic expression of either Bcl-XL or the constitutively active AMPK mutant
      significantly rescued DP thymocytes from LKB1 deficiency-induced cell death.
      Moreover, ectopic expression of the constitutively active AMPK mutant was found
      to restore the expression of Bcl-XL in LKB1-deficient DP thymocytes. These
      findings identify LKB1 as a critical factor for the survival of DP thymocytes
      through regulation of AMPK activation and Bcl-XL expression.

PMID- 20029390
TI  - Quick to remember, slow to forget: rapid recall responses of memory CD8+ T cells.
AB  - The functional roles of memory B and T lymphocytes underlie the phenomenal
      success of prophylactic vaccinations, which have decreased morbidities and
      mortalities from infectious diseases globally over the last 50 years. However, it
      is becoming increasingly appreciated that memory cells are also capable of
      mediating the pathology associated with autoimmune disorders and transplant
      rejection, and may pose a significant barrier to future clinical advancement in
      immunoregulation. Therefore, understanding the unique properties of memory
      lymphocytes (as compared to their naive precursors) is a major area of
      investigation. Here, we focus on one of those singular properties of memory T
      cells (T(M))-rapid recall. As will be discussed in more detail, rapid recall
      refers to the ability of quiescent T(M) cells to efficiently and robustly express
      'effector functions' following stimulation. Studies that have advanced our
      understanding of T(M) cells' rapid recall using CD4(+) T cells have been expertly
      reviewed elsewhere, so we will focus primarily on studies of CD8(+) T cells. We
      will first review the different ways that CD8(+) T(M) cells can be generated,
      followed by discussing how this influences their functional properties in the
      settings of immune protection and pathology. Then, rapid recall ability will be
      discussed, with emphasis placed on what is currently known about the mechanisms
      that underlie this unique property of T(M) cells.

PMID- 20029391
TI  - Sex differences in orbitofrontal gray as a partial explanation for sex
      differences in antisocial personality.
AB  - Attention is increasingly being given to understanding sex difference in
      psychopathology to better understand the etiology of disorders. This study tests
      the hypothesis that sex differences in ventral and middle frontal gray volume
      contribute to sex differences in antisocial personality disorder (APD) and crime.
      Participants were recruited from temporary employment agencies, consisting of
      normal controls, substance/alcohol-dependent controls, axis I/II psychiatric
      controls and individuals with APD. An independent sample of female volunteers was
      also recruited. Magnetic resonance imaging volumes of superior frontal, middle
      frontal, inferior frontal, orbital frontal and rectal gyral frontal gray matter,
      and dimensional scores of APD and criminal behavior were assessed. APD males when
      compared with male controls showed an 8.7% reduction in orbitofrontal gray
      volume, a 17.3% reduction in middle frontal gray and a 16.1% reduction in right
      rectal gray. Reduced middle and orbitofrontal volumes were significantly
      associated with increased APD symptoms and criminal offending in both males and
      females. Males as a whole had reduced orbitofrontal and middle frontal gray
      volume when compared with females, and controlling for these brain differences
      reduced the gender difference in the antisocial personality/behavior by 77.3%.
      Findings were not a function of psychiatric comorbidity, psychosocial risk
      factors, head injury or trauma exposure. Findings implicate structural
      differences in the ventral and middle frontal gray as both a risk factor for APD
      and as a partial explanation for sex differences in APD.

PMID- 20029392
TI  - Medical conditions and outcomes at 1 year after acute traumatic spinal cord
      injury in a Greek and a Swedish region: a prospective, population-based study.
AB  - STUDY DESIGN: Prospective, population-based study. This paper is part of the
      Stockholm Thessaloniki Acute Traumatic Spinal Cord Injury Study (STATSCIS).
      OBJECTIVES: To evaluate and compare outcomes, length of stay (LOS), associated
      conditions and medical complications at 1-year post-trauma. SETTINGS: The Greater
      Thessaloniki region, Greece, and the Greater Stockholm region, Sweden. While
      Stockholm follows a SCI system of care, Thessaloniki follows a fragmented 'non
      system' approach. SUBJECTS: Out of the 87 cases in Thessaloniki and the 49 cases
      in Stockholm who comprised the study population of STATSCIS, 75 and 42 cases
      respectively were successfully followed-up during the first year post-trauma.
      RESULTS: Significantly superior outcomes (that is, survival with neurological
      recovery, functional ability and discharge to home) and shorter LOS for initially
      motor complete cases occurred in Stockholm. Management routines known to increase
      long-term morbidity, for example, long-term tracheostomy and indwelling urethral
      catheters were significantly more common in Thessaloniki. Major medical
      complications, that is, multiple pressure ulcers, heterotopic ossification and
      bacteremia/sepsis were more frequent in Thessaloniki. CONCLUSIONS: Our findings
      show how two rather similar cohorts of TSCI manifest large discrepancies in terms
      of 1-year outcomes and complications, depending on the type of management they
      receive. As the major difference between regions was the presence or absence of a
      SCI system of care, rather than differences in availability of modern medicine,
      the mere presence of the latter does not seem to be sufficient to guarantee
      adequate outcomes. This study provides strong evidence as to the urgent need of
      implementing a SCI system of care in Greece.

PMID- 20029394
TI  - Psychological intervention during spinal rehabilitation: a preliminary study.
AB  - STUDY DESIGN: A repeated measures, non-randomised controlled trial. OBJECTIVE: To
      examine the effectiveness of individualised cognitive behaviour therapy (CBT) on
      the psychological adjustment of patients undergoing rehabilitation for newly
      acquired spinal cord injury. SETTING: South Australian Spinal Cord Injury
      Service, Hampstead Rehabilitation Centre, South Australia, Australia. METHODS:
      Eleven participants received individual CBT as part of their spinal
      rehabilitation. Self-reported levels of depression, anxiety and stress were
      assessed before the intervention, at week 12 of rehabilitation and at 3 months
      post-discharge, using the depression, anxiety and stress scales (DASS-21).
      Functional independence was also assessed, using the Functional Independence
      Measure (FIM). Responses were compared with 13 participants, closely matched on
      demographic and injury variables, who received standard psychological care (that
      is, assessment and monitoring only). RESULTS: Depression scores for treatment
      participants showed a significant time effect, with worsening symptoms reported
      at three-month follow-up, after CBT was discontinued. In contrast, the DASS-21
      scores of standard care participants remained at subclinical levels throughout
      the study. Clinical improvements in symptoms of anxiety and stress were also
      reported by the treatment group as inpatient therapy progressed. CONCLUSION:
      Targeted, individualised psychological treatment contributed to short-term,
      meaningful improvements in emotional outcomes for individuals reporting
      psychological morbidity after recent spinal injury. The results also highlight
      the need for ongoing access to specialised, psychological services post
      discharge. Replication of these results with a larger sample is required before
      definitive conclusions can be drawn.

PMID- 20029393
TI  - Quality of life instruments and definitions in individuals with spinal cord
      injury: a systematic review.
AB  - STUDY DESIGN: A systematic review. OBJECTIVE: To critically review quality of
      life (QOL) instruments used with spinal cord injury (SCI) populations. SETTING:
      Vancouver, Canada. METHODS: A systematic literature review was conducted for
      publications assessing the measurement properties of QOL outcome measures. Pre
      established criteria were used to evaluate the measurement properties. RESULTS:
      Fourteen articles reporting on 13 QOL instruments met the inclusion criteria,
      including the Patient Reported Impact of Spasticity Measure (PRISM), Quality of
      Well-being Scale, Qualiveen, Sickness Impact Profile (SIP68), Short Form (SF)-36,
      SF-36V, SF-12, SF-6D, Quality of Life Index, Quality of Life Profile for Adults
      with Physical Disabilities (QOLP-PD), Satisfaction with Life Scale, Sense of Well
      being Index (SWBI), and the World Health Organization Quality of Life-BREF scale
      (WHOQOL-BREF). The SF-36 and WHOQOL-BREF have been widely used and validated. The
      SIP68, QOLP-PD, SF-36V, and SWBI are promising with limited investigation. The
      Qualiveen and PRISM performed well and are specific to SCI complications.
      CONCLUSION: The WHOQOL-BREF is presently the most acceptable and established
      instrument to assess QOL after SCI. The SIP68, QOLP-PD, SF-36V, and SWBI are
      promising; however, require further evaluation of their measurement properties.

PMID- 20029395
TI  - Development of an international spinal injury prevention module: application of
      the international classification of external cause of injury to spinal cord
      injury.
AB  - STUDY DESIGN: An end-user response survey and assessments of inter-rater
      reliability before and after training. OBJECTIVES: Evaluate the spinal cord
      injury (SCI) application of the international classification of external cause of
      injury (ICECI) in a mixed group of untrained and trained coders to assess
      agreement, refine coding and training methodology. SETTING: An interactive coding
      workshop for an international group of coders with varying previous training.
      METHODS: Evaluate content validity (qualitative survey) and inter-rater
      reliability (kappa estimate of agreement) of the ICECI in a variety of injury
      scenarios presented within a computerized data-entry and training module. The
      results of this evaluation are compared with an earlier published gold standard.
      RESULTS: The ICECI is a flexible data coding system that appears to work with
      reasonable content validity in the regions assessed with English-language coders.
      Training appeared to narrow the difference between the inexperienced and trained
      coders. This is reflected in a borderline tendency for lower kappa scores pre
      training compared with an earlier examined group of expert coders (P=0.073) but
      no difference in kappa scores after training (P=0.67). Computer-based training on
      a face-to-face level with computerized data entry appears an effective tool for
      training coders to use the ICECI. CONCLUSIONS: This report shows that using
      electronic data-entry and training assistance, inexperienced coders using the SCI
      ICECI computerized system quickly approach the levels of agreement of trained
      coders in related data systems. The content validity of the training data set is
      adequate but needs to include more cases representative for use in SCI.

PMID- 20029396
TI  - Acute management of traumatic spinal cord injury in a Greek and a Swedish region:
      a prospective, population-based study.
AB  - STUDY DESIGN: Prospective, population-based study. This paper is part of the
      Stockholm Thessaloniki Acute Traumatic Spinal Cord Injury Study (STATSCIS).
      OBJECTIVES: To characterize patient populations and to compare acute management
      after traumatic spinal cord injury (TSCI). SETTINGS: The Greater Thessaloniki
      region in Greece and the Greater Stockholm region in Sweden. METHODS: Inception
      cohorts with acute TSCI that were hospitalized during the study period, that is
      September 2006 to October 2007, were identified. Overall, 81 out of 87 cases
      consented to inclusion in Thessaloniki and 47 out of 49 in Stockholm. Data from
      Thessaloniki were collected through physical examinations, medical record reviews
      and communication with TSCI cases and medical teams. Data from Stockholm were
      retrieved from the Nordic Spinal Cord Injury Registry. RESULTS: There were no
      significant differences between study groups with regard to core clinical
      characteristics. In contrast, there were significant differences in (1) transfer
      logistics from the scene of trauma to a tertiary-level hospital (number of
      intermediate admissions, modes of transportation and duration of transfer) and
      (2) acute key therapeutic interventions, that is, the use of mechanical
      ventilation (49% in Thessaloniki versus 20% in Stockholm), and performance of
      tracheostomy (36% in Thessaloniki versus 15% in Stockholm); spinal surgery was
      performed significantly more often and earlier in Stockholm than in Thessaloniki.
      CONCLUSIONS: Despite largely similar core clinical characteristics, Stockholm and
      Thessaloniki cases underwent significantly different acute management, most
      probably to be attributed to adaptations to the differing regional approaches of
      care one following a systematic approach of SCI care and the other not.

PMID- 20029398
TI  - Reducible poly(oligo-D-arginine) for enhanced gene expression in mouse lung by
      intratracheal injection.
AB  - Nonarginine (D-R9) has been reported to be one of the most efficacious protein
      transduction domains (PTDs) for the intracellular cargo delivery such as DNA,
      RNA, proteins, and particles. Although oligoarginines are capable of forming
      polyplex with DNA by electrostatic interaction, the length of oligoarginine can
      affect the toxicity and gene expression. The reducible poly(oligo-D-arginine)
      (rPOA) composed of the Cys-(D-R9)-Cys repeating unit forming disulfide bonds
      between terminal cysteinyl-thiol groups of short peptides was hypothesized to
      show efficient gene transfection without toxicity. The reducible high molecular
      weight poly(oligo-D-arginine) may fragment into the Cys-(D-R9)-Cys in cellular
      environments such as cytosol, cell surface, endosomes, and lysosomes, and enhance
      DNA transfection efficiency. In the present study, in vitro stability,
      cytotoxicity, and transfection efficiency of DNA/poly(oligo-D-arginine) polyplex
      were evaluated. In addition, in vivo delivery of DNA into the lung was performed
      by intratracheal injection of DNA/poly(oligo-D-arginine) polyplex. The in vivo
      study with rPOA showed higher level of gene expression than PEI, sustaining for 1
      week without toxicity. Reducible high molecular weight poly(oligo-D-arginine)
      based on R9 PTD is a very promising nonviral gene carrier for lung diseases by
      efficiently condensing, stabilizing, and transfecting DNA.

PMID- 20029397
TI  - Adoptive transfer of ex vivo HO-1 modified bone marrow-derived macrophages
      prevents liver ischemia and reperfusion injury.
AB  - Macrophages play a critical role in the pathophysiology of liver ischemia and
      reperfusion (IR) injury (IRI). However, macrophages that overexpress antioxidant
      heme oxygenase-1 (HO-1) may exert profound anti-inflammatory functions. This
      study explores the cytoprotective effects and mechanisms of ex vivo modified HO-1
      expressing bone marrow-derived macrophages (BMDMs) in well-defined mouse model of
      liver warm ischemia followed by reperfusion. Adoptive transfer of Ad-HO-1
      transduced macrophages prevented IR-induced hepatocellular damage, as evidenced
      by depressed serum glutamic-oxaloacetic transaminase (sGOT) levels and preserved
      liver histology (Suzuki scores), compared to Ad-beta-gal controls. This
      beneficial effect was reversed following concomitant treatment with HO-1 siRNA.
      Ad-HO-1-transfected macrophages significantly decreased local neutrophil
      accumulation, TNF-alpha/IL-1beta, IFN-gamma/E-selectin, and IP-10/MCP-1
      expression, caspase-3 activity, and the frequency of apoptotic cells, as compared
      with controls. Unlike in controls, Ad-HO-1-transfected macrophages markedly
      increased hepatic expression of antiapoptotic Bcl-2/Bcl-xl and depressed caspase
      3 activity. These results establish the precedent for a novel investigative tool
      and provide the rationale for a clinically attractive new strategy in which
      native macrophages can be transfected ex vivo with cytoprotective HO-1 and then
      infused, if needed, to prospective recipients exposed to hepatic IR-mediated
      local inflammation, such as during liver transplantation, resection, or trauma.

PMID- 20029400
TI  - Novel role for the transient receptor potential channel TRPM2 in prostate cancer
      cell proliferation.
AB  - We have identified a novel function for a member of the transient receptor
      potential (TRP) protein super-family, TRPM2, in prostate cancer cell
      proliferation. TRPM2 encodes a non-selective cation-permeable ion channel. We
      found that selectively knocking down TRPM2 with the small interfering RNA
      technique inhibited the growth of prostate cancer cells but not of non-cancerous
      cells. The subcellular localization of this protein is also remarkably different
      between cancerous and non-cancerous cells. In BPH-1 (benign), TRPM2 protein is
      homogenously located near the plasma membrane and in the cytoplasm, whereas in
      the cancerous cells (PC-3 and DU-145), a significant amount of the TRPM2 protein
      is located in the nuclei in a clustered pattern. Furthermore, we have found that
      TRPM2 inhibited nuclear ADP-ribosylation in prostate cancer cells. However, TRPM2
      knockdown-induced inhibition of proliferation is independent of the activity of
      poly(ADP-ribose) polymerases. We conclude that TRPM2 is essential for prostate
      cancer cell proliferation and may be a potential target for the selective
      treatment of prostate cancer.

PMID- 20029401
TI  - Upgrading of Gleason score 6 prostate cancers on biopsy after prostatectomy in
      the low and intermediate tPSA range.
AB  - When offering watchful waiting or active monitoring protocols to prostate cancer
      (PCa) patients, differentiation between Gleason scores (GS) 6 and 7 at biopsy is
      important. However, upgrading after prostatectomy is common. We investigated the
      impact of different PSA levels on misclassification in the PSA range of 2-3.9 and
      4-10 ng ml(-1). A total of 448 patients with GS 6 PCa on prostate biopsy were
      evaluated by comparing biopsy and prostatectomy GS. Possible over diagnosis was
      defined as GS <7, pathological stage pT2a and negative surgical margins, and
      possible under diagnosis was defined as pT3a or greater, or positive surgical
      margins; the percentage of over- or under diagnosis was determined for correctly
      and upgraded tumors after prostatectomy. A match between biopsy and prostatectomy
      GS was found in 210 patients (46.9%). Patients in the PSA range of 2.0-3.9 and
      4.0-10.0 ng ml(-1) were upgraded in 32.6 and 44.0%, respectively. Over diagnosis
      was more common than under diagnosis (23.2% vs 15.6%). When upgraded there was a
      significant increase in under diagnosis. As almost 40% of GS 6 tumors on biopsy
      are GS 7 or higher after surgery with a significant rise in under diagnosis there
      is a risk of misclassification and subsequent delayed or even insufficient
      treatment, when relying on favorable biopsy GS.

PMID- 20029399
TI  - Intelligent design: combination therapy with oncolytic viruses.
AB  - Metastatic cancer remains an incurable disease in the majority of cases and thus
      novel treatment strategies such as oncolytic virotherapy are rapidly advancing
      toward clinical use. In order to be successful, it is likely that some type of
      combination therapy will be necessary to have a meaningful impact on this
      disease. Although it may be tempting to simply combine an oncolytic virus with
      the existing standard radiation or chemotherapeutics, the long-term goal of such
      treatments must be to have a rational, potentially synergistic combination
      strategy that can be safely and easily used in the clinical setting. The
      combination of oncolytic virotherapy with existing radiotherapy and chemotherapy
      modalities is reviewed along with novel biologic therapies including
      immunotherapies, in order to help investigators make intelligent decisions during
      the clinical development of these products.

PMID- 20029402
TI  - Obesity-PSA relationship: a new formula.
AB  - To clinically apply the inverse PSA-body mass index (BMI) correlation and enhance
      PSA sensitivity in obese cases, a new formula is warranted. An innovated BMI-PSA
      equation is designed. PSA-BMI adjusted formula (named Hekal's equation): measured
      total PSA (ng ml(-1)) multiplied by age (years) and divided by BMI of the
      patient. The formula is applied over a randomly chosen 1000 cases of different
      PSA, BMI, age and trans-rectal ultrasound biopsy results, the yield of new PSA is
      correlated with pathology and age-specific PSA adjustment values. Among the 988
      cases with complete data, obesity (BMI: 30-35 kg m(-2)) in 236 cases (23.8%) and
      79 cases (7.9%) have BMI>35 kg m(-2). Mean PSA was 5.8 ng ml(-1) (s.d.+/-8.4 ng
      ml(-1)). Cases stratified based on their age (every 10 years). The new equation
      was applied. Obesity is detected in 33.5 and 43.6% of fifth and sixth decade of
      life respectively (P=0.02), with low measured PSA values (2.1, 3.8 ng ml(-1),
      respectively). By such PSA measurement biopsy may be omitted, missing 53.3% of
      malignant cases. In contrast, PSA adjusted were 4 and 9.3 ng ml(-1) within the
      same group of patients. With such values, the decision of a biopsy could not be
      missed for the targeted groups. Specificity and sensitivity of adjusted PSA
      values at cutoff point 4 ng ml(-1) was 41.7 and 70%, respectively. Based on our
      results, the new PSA-BMI adjusted formula is reproducible, easy applied formula.
      With such a formula the higher sensitivity of PSA in obese patients could be
      achieved. The misleading low PSA in obese cases in the fifth and sixth decade
      will be corrected.

PMID- 20029403
TI  - Potential diagnostic markers for postpartum depression point out to altered
      immune signaling.

PMID- 20029405
TI  - Elevated S100B levels in schizophrenia are associated with insulin resistance.

PMID- 20029406
TI  - Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with
      bipolar disorder and visual processing.

PMID- 20029407
TI  - Prenatal exposure to maternal cigarette smoking interacts with a polymorphism in
      the alpha6 nicotinic acetylcholine receptor gene to influence drug use and
      striatum volume in adolescence.

PMID- 20029408
TI  - A canine chromosome 7 locus confers compulsive disorder susceptibility.

PMID- 20029409
TI  - Association of polymorphisms in the SLIT2 axonal guidance gene with anger in
      suicide attempters.

PMID- 20029410
TI  - The 2009 Nobel conference on the role of genetics in promoting suicide prevention
      and the mental health of the population.
AB  - A 3-day Nobel Conference entitled 'The role of genetics in promoting suicide
      prevention and the mental health of the population' was held at the Nobel Forum,
      Karolinska Institute (KI) in Stockholm, Sweden, during 8-10 June 2009. The
      conference was sponsored by the Nobel Assembly for Physiology or Medicine and
      organized by the National Prevention for Suicide and Mental Ill-Health and the
      Center for Molecular Medicine at KI. The program consisted of 19 invited
      presentations, covering the genetic basis of mood/psychotic disorders and
      substance abuse in relation to suicide, with topics ranging from cellular
      molecular mechanisms to (endo)phenotypes of mental disorders at the level of the
      individual and populations. Here, we provide an overview based on the highlights
      of what was presented.

PMID- 20029411
TI  - The moderation by the serotonin transporter gene of environmental adversity in
      the etiology of depression: 2009 update.
AB  - An updated review of 34 human observational studies indicates that the length
      polymorphism of the serotonin transporter gene moderates the effect of
      environmental adversity in the development of depression. This finding depends on
      the use of contextual or objective methods to assess environmental adversity and
      is attenuated when self-report instruments are used. Inconsistent findings in
      male adolescents suggest a developmental stage and sex-specific protective
      mechanism. These systematic relationships between method and results should be
      followed up to specify causal mechanisms leading to depression.

PMID- 20029412
TI  - Capsule endoscopy has a significantly higher diagnostic yield in patients with
      suspected and established small-bowel Crohn's disease: a meta-analysis.
AB  - OBJECTIVES: Capsule endoscopy (CE) has demonstrated superior performance compared
      with other modalities in its ability to detect early small-bowel (SB) Crohn's
      disease (CD), especially when ileoscopy is negative or unsuccessful. The aim of
      this study was to evaluate the diagnostic yield of CE compared with other
      modalities in patients with suspected and established CD using a meta-analysis.
      METHODS: A thorough literature search for prospective studies comparing the
      diagnostic yield of CE with other modalities in patients with CD was undertaken.
      Other modalities included push enteroscopy (PE), colonoscopy with ileoscopy
      (C+IL), SB radiography (SBR), computed tomography enterography (CTE), and
      magnetic resonance enterography (MRE). Data on diagnostic yield among various
      modalities were extracted, pooled, and analyzed. Data on patients with suspected
      and established CD were analyzed separately. Weighted incremental yield (IYW)
      (diagnostic yield of CE-diagnostic yield of comparative modality) and 95%
      confidence intervals (CIs) of CE over comparative modalities were calculated.
      RESULTS: A total of 12 trials (n=428) compared the yield of CE with SBR in
      patients with CD. Eight trials (n=236) compared CE with C+IL, four trials (n=119)
      compared CE with CTE, two trials (n=102) compared CE with PE, and four trials
      (n=123) compared CE with MRE. For the suspected CD subgroup, several comparisons
      met statistical significance. Yields in this subgroup were CE vs. SBR: 52 vs. 16%
      (IYw=32%, P<0.0001, 95% CI=16-48%), CE vs. CTE: 68 vs. 21% (IYw=47%, P<0.00001,
      95% CI=31-63%), and CE vs. C+IL: 47 vs. 25% (IYw=22%, P=0.009, 95% CI=5-39%).
      Statistically significant yields for CE vs. an alternate diagnostic modality in
      established CD patients were seen in CE vs. PE: 66 vs. 9% (IYw=57%, P<0.00001,
      95% CI=43-71%), CE vs. SBR: 71 vs. 36% (IYw=38%, P<0.00001, 95% CI=22-54%), and
      in CE vs. CTE: 71 vs. 39% (IYw=32%, P=or<0.0001, 95% CI=16-47%). CONCLUSIONS: Our
      meta-analysis demonstrates that CE is superior to SBR, CTE, and C+IL in the
      evaluation of suspected CD patients. CE is also a more effective diagnostic tool
      in established CD patients compared with SBR, CTE, and PE.

PMID- 20029413
TI  - Role of esophageal stents in benign and malignant diseases.
AB  - These recommendations provide an evidence-based approach to the role of
      esophageal stents in the management of benign and malignant diseases. These
      guidelines have been developed under the auspices of the American College of
      Gastroenterology and its Practice Parameters Committee and approved by the Board
      of Trustees. The following guidelines are based on a critical review of the
      available scientific literature on the topic identified in Medline and PubMed
      (January 1992-December 2008) using search terms that included stents, self
      expandable metal stents, self-expandable plastic stents, esophageal cancer,
      esophageal adenocarcinoma, esophageal squamous cell carcinoma, esophageal
      stricture, perforations, anastomotic leaks, tracheoesophageal fistula, and
      achalasia. These guidelines are intended for use by health-care providers and
      apply to adult, but not pediatric, patients. As with other practice guidelines,
      these guidelines are not intended to replace clinical judgment but rather to
      provide general guidelines applicable to the majority of patients. Clinicians
      need to integrate recommendations with their own clinical judgment, and with
      individual patient circumstances, values, and preferences. They are intended to
      be flexible, in contrast to standards of care, which are inflexible policies
      designed to be followed in every case. Specific recommendations are based on
      relevant published information. The quality of evidence and strength of
      recommendations have been assessed using the Grading of Recommendations
      Assessment, Development, and Evaluation (GRADE) system, which is a system that
      has been adopted by multiple national and international societies. The GRADE
      system is based on a sequential assessment of quality of evidence, followed by
      assessment of the balance between benefits vs. downsides (harms, burden, and
      costs) and subsequent judgment regarding the strength of recommendation.

PMID- 20029415
TI  - Methodology for randomized trials of patients with nonvariceal upper
      gastrointestinal bleeding: recommendations from an international consensus
      conference.
AB  - The aim of this document is to provide a methodological framework for the design,
      performance, analysis, interpretation, and communication of randomized trials
      that assess management of patients with nonvariceal upper gastrointestinal
      bleeding. Literature searches were performed and an iterative process with
      electronic and face-to-face meetings was used to achieve consensus among panel
      members as part of an International Consensus Conference on Nonvariceal Upper
      Gastrointestinal Bleeding. Recommendations of the panel include the following.
      Randomized trials must explicitly state their primary hypothesis. A
      nonmanipulable randomization schedule with concealed allocation should be used.
      Stratification (e.g., for age and stigmata of hemorrhage) may be considered,
      especially in smaller studies. The patient and personnel providing care or
      recording information should be blinded. Inclusion criteria should be overt
      bleeding with endoscopy performed within 24 h or less. One type of lesion (e.g.,
      ulcer) should be studied with stigmata to be included predefined. Use of
      placebo/no therapy vs. active controls depends on current standard practice.
      Standardizing study and key non-study interventions should ensure uniform
      provision of interventions. Criteria for repeat endoscopy and subsequent
      interventions should be predefined. The primary end point should be further
      bleeding (persistent and recurrent bleeding) with primary assessment at 7 days;
      mortality, with primary assessment at 30 days, would be appropriate in very large
      trials. Sample size calculation based on assumptions regarding primary end point
      results with regard to study intervention and control must be provided, and all
      patients enrolled must be accounted for. In general, the primary population for
      analysis is all patients randomized, although a per-protocol population may be
      used if this is the more conservative approach (e.g., equivalence study).

PMID- 20029414
TI  - Appropriateness guidelines and predictive rules to select patients for upper
      endoscopy: a nationwide multicenter study.
AB  - OBJECTIVES: Selecting patients appropriately for upper endoscopy (EGD) is crucial
      for efficient use of endoscopy. The objective of this study was to compare
      different clinical strategies and statistical methods to select patients for EGD,
      namely appropriateness guidelines, age and/or alarm features, and multivariate
      and artificial neural network (ANN) models. METHODS: A nationwide, multicenter,
      prospective study was undertaken in which consecutive patients referred for EGD
      during a 1-month period were enrolled. Before EGD, the endoscopist assessed
      referral appropriateness according to the American Society for Gastrointestinal
      Endoscopy (ASGE) guidelines, also collecting clinical and demographic variables.
      Outcomes of the study were detection of relevant findings and new diagnosis of
      malignancy at EGD. The accuracy of the following clinical strategies and
      predictive rules was compared: (i) ASGE appropriateness guidelines (indicated vs.
      not indicated), (ii) simplified rule (>or=45 years or alarm features vs. <45
      years without alarm features), (iii) logistic regression model, and (iv) ANN
      models. RESULTS: A total of 8,252 patients were enrolled in 57 centers. Overall,
      3,803 (46%) relevant findings and 132 (1.6%) new malignancies were detected.
      Sensitivity, specificity, and area under the receiver-operating characteristic
      curve (AUC) of the simplified rule were similar to that of the ASGE guidelines
      for both relevant findings (82%/26%/0.55 vs. 88%/27%/0.52) and cancer
      (97%/22%/0.58 vs. 98%/20%/0.58). Both logistic regression and ANN models seemed
      to be substantially more accurate in predicting new cases of malignancy, with an
      AUC of 0.82 and 0.87, respectively. CONCLUSIONS: A simple predictive rule based
      on age and alarm features is similarly effective to the more complex ASGE
      guidelines in selecting patients for EGD. Regression and ANN models may be useful
      in identifying a relatively small subgroup of patients at higher risk of cancer.

PMID- 20029416
TI  - Differential miRNA expression profiles in variants of papillary thyroid carcinoma
      and encapsulated follicular thyroid tumours.
AB  - BACKGROUND: Recent studies showed a significant upregulation of distinct
      microRNAs (miRNAs) in papillary thyroid carcinoma (PTC). The objective of this
      study was to explore whether this upregulation could also be assigned to distinct
      histomorphological variants of PTC, especially the follicular variant and other
      encapsulated follicular thyroid tumours. METHODS: We used total RNA of 113
      formalin-fixed paraffin-embedded tissues of 50 PTCs ((10 conventional type (PTC
      CT), 10 tall cell variants (PTC-TCVs), 30 follicular variants (PTC-FVs)), 10
      follicular adenomas (FAs), 10 multinodular goitres (MNGs), 21 follicular thyroid
      carcinomas and 22 well-differentiated tumours of unknown malignant potential (WDT
      UMP) to analyse the miRNA expression pattern of five selected miRNAs (146b, 181b,
      21, 221 and 222) using RT-PCR TaqMan miRNA assay to explore the diagnostic
      utility of this method. RESULTS: The mean values of the expression pattern of all
      miRNAS in PTCs show a statistically significant difference from those in MNG and
      FA with fold changes up to 90 for miRNA 146b, P<0.001. No differences in
      expression pattern could be showed between MNG and FA. The PTC-FVs differ
      significantly from FA in all five miRNAS, from MNG in three and from WDT-UMP in
      one miRNA with fold changes between 1.7 and 21.2, but failed to be of diagnostic
      value regarding individual cases with substantial overlaps. CONCLUSION: We
      conclude that analysis of a set of five selected miRNAS distinguish common
      variants of PTC from FA/MNG but failed to be a useful diagnostic method in
      individual and doubtful cases, especially in the differential diagnosis of
      encapsulated follicular thyroid tumours.

PMID- 20029417
TI  - Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated
      cytotoxicity in patients with oesophageal squamous cell carcinoma.
AB  - BACKGROUND: We previously reported that Trastuzumab- and Cetuximab-mediated
      antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer patients was
      impaired in comparison with that in healthy donors because of NK-cell
      dysfunction. In this study, we evaluated whether IL-21 could improve the
      impairment of ADCC in patients with oesophageal squamous cell carcinoma (ESCC),
      as IL-21 was reported to have the ability to activate NK cells. METHODS: We
      examined Trastuzumab- and Cetuximab-mediated ADCC of peripheral blood mononuclear
      cells (PBMCs) or of enriched NK cells derived from ESCC patients (n=20) and
      healthy donors (n=16) in the presence of IL-21. We further analysed ADCC-related
      molecules (perforin, granzyme-B, and CD247) on NK cells in response to IL-21.
      RESULTS: Trastuzumab- and Cetuximab-mediated ADCC of PBMCs or of enriched NK
      cells was enhanced by the addition of IL-21 in a dose-dependent manner and the
      levels of ADCC enhanced by IL-21 in patients were high enough in comparison with
      those in healthy donors, paralleling the upregulation of CD247 on NK cells.
      CONCLUSION: IL-21 could efficiently restore impaired ADCC in ESCC patients with
      the upregulation of CD247 molecules.

PMID- 20029418
TI  - Class III beta-tubulin expression and in vitro resistance to microtubule
      targeting agents.
AB  - BACKGROUND: Class III beta-tubulin overexpression is a marker of resistance to
      microtubule disruptors in vitro, in vivo and in the clinic for many cancers,
      including breast cancer. The aims of this study were to develop a new model of
      class III beta-tubulin expression, avoiding the toxicity associated with chronic
      overexpression of class III beta-tubulin, and study the efficacy of a panel of
      clinical and pre-clinical drugs in this model. METHODS: MCF-7 (ER+ve) and MDA-MB
      231 (ER-ve) were either transfected with pALTER-TUBB3 or siRNA-tubb3 and 24 h
      later exposed to test compounds for a further 96 h for proliferation studies. RT
      PCR and immunoblotting were used to monitor the changes in class III beta-tubulin
      mRNA and protein expression. RESULTS: The model allowed for subtle changes in
      class III beta-tubulin expression to be achieved, which had no direct effect on
      the viability of the cells. Class III beta-tubulin overexpression conferred
      resistance to paclitaxel and vinorelbine, whereas downregulation of class III
      beta-tubulin rendered cells more sensitive to these two drugs. The efficacy of
      the colchicine-site binding agents, 2-MeOE2, colchicine, STX140, ENMD1198 and
      STX243 was unaffected by the changes in class III beta-tubulin expression.
      CONCLUSION: These data indicate that the effect of class III beta-tubulin
      overexpression may depend on where the drug's binding site is located on the
      tubulin. Therefore, this study highlights for the first time the potential key
      role of targeting the colchicine-binding site, to develop new treatment
      modalities for taxane-refractory breast cancer.

PMID- 20029419
TI  - Whole-genome cancer analysis as an approach to deeper understanding of tumour
      biology.
AB  - Recent advances in DNA sequencing technology are providing unprecedented
      opportunities for comprehensive analysis of cancer genomes, exomes,
      transcriptomes, as well as epigenomic components. The integration of these data
      sets with well-annotated phenotypic and clinical data will expedite improved
      interventions based on the individual genomics of the patient and the specific
      disease.

PMID- 20029420
TI  - BRCA1 and its toolbox for the maintenance of genome integrity.
AB  - The breast and ovarian cancer type 1 susceptibility protein (BRCA1) has pivotal
      roles in the maintenance of genome stability. Studies support that BRCA1 exerts
      its tumour suppression function primarily through its involvement in cell cycle
      checkpoint control and DNA damage repair. In addition, recent proteomic and
      genetic studies have revealed the presence of distinct BRCA1 complexes in vivo,
      each of which governs a specific cellular response to DNA damage. Thus, BRCA1 is
      emerging as the master regulator of the genome through its ability to execute and
      coordinate various aspects of the DNA damage response.

PMID- 20029421
TI  - Integrins in cancer: biological implications and therapeutic opportunities.
AB  - The integrin family of cell adhesion receptors regulates a diverse array of
      cellular functions crucial to the initiation, progression and metastasis of solid
      tumours. The importance of integrins in several cell types that affect tumour
      progression has made them an appealing target for cancer therapy. Integrin
      antagonists, including the alphavbeta3 and alphavbeta5 inhibitor cilengitide,
      have shown encouraging activity in Phase II clinical trials and cilengitide is
      currently being tested in a Phase III trial in patients with glioblastoma. These
      exciting clinical developments emphasize the need to identify how integrin
      antagonists influence the tumour and its microenvironment.

PMID- 20029423
TI  - Senescence in tumours: evidence from mice and humans.
AB  - The importance of cellular senescence, which is a stress response that stably
      blocks proliferation, is increasingly being recognized. Senescence is prevalent
      in pre-malignant tumours, and progression to malignancy requires evading
      senescence. Malignant tumours, however, may still undergo senescence owing to
      interventions that restore tumour suppressor function or inactivate oncogenes.
      Senescent tumour cells can be cleared by immune cells, which may result in
      efficient tumour regression. Standard chemotherapy also has the potential to
      induce senescence, which may partly underlie its therapeutic activity. Although
      these concepts are well supported in mouse models, translating them to clinical
      oncology remains a challenge.

PMID- 20029422
TI  - Leukaemogenesis: more than mutant genes.
AB  - Acute leukaemias are characterized by recurring chromosomal aberrations and gene
      mutations that are crucial to disease pathogenesis. It is now evident that
      epigenetic modifications, including DNA methylation and histone modifications,
      substantially contribute to the phenotype of leukaemia cells. An additional layer
      of epigenetic complexity is the pathogenetic role of microRNAs in leukaemias, and
      their key role in the transcriptional regulation of tumour suppressor genes and
      oncogenes. The genetic heterogeneity of acute leukaemias poses therapeutic
      challenges, but pharmacological agents that target components of the epigenetic
      machinery are promising as a component of the therapeutic arsenal for this group
      of diseases.

PMID- 20029424
TI  - A census of amplified and overexpressed human cancer genes.
AB  - Integrated genome-wide screens of DNA copy number and gene expression in human
      cancers have accelerated the rate of discovery of amplified and overexpressed
      genes. However, the biological importance of most of the genes identified in such
      studies remains unclear. In this Analysis, we propose a weight-of-evidence based
      classification system for identifying individual genes in amplified regions that
      are selected for during tumour development. In a census of the published
      literature we have identified 77 genes for which there is good evidence of
      involvement in the development of human cancer.

PMID- 20029426
TI  - The right to choose parenthood among HIV-infected women and men.
AB  - As life expectancy for HIV-infected persons improves, studies in sub-Saharan
      Africa show that a considerable proportion of HIV-positive women and men desire
      to have children. Integrating sexual and reproductive health care into HIV
      services has until now emphasized the right of women to make informed choices
      about their reproductive lives and the right of self-determination to reproduce,
      but this is often equated with avoidance of pregnancy. Here, we explore guidance
      and attention to safer conception for HIV-infected women and men. We find this
      right lacking. Current sexual and reproductive health guidelines are not
      proactive in supporting HIV-positive people desiring children, and are
      particularly silent about the fertility needs of HIV-infected men and uninfected
      men in discordant partnerships. Public health policymakers and providers need to
      engage the HIV-infected and uninfected to determine both the demand for and how
      best to address the need for safer conception services.

PMID- 20029427
TI  - How China responded to the May 2008 earthquake during the emergency and rescue
      period.
AB  - This article describes the overall damage caused by the May 2008 earthquake in
      Beichuan County of Sichuan Province in China and the response over the initial
      three-month 'Emergency Response and Rescue Period' as defined by the Chinese
      government. We hope to inform people by sharing observations and that lessons
      from the earthquake can be learned in order to make response to similar disasters
      more effective in future. We used questionnaires to collect data from the County
      government authorities, including the health bureau, civil affairs bureau, county
      hospital, and authorities in four townships, four township hospitals, and four
      village health posts. In addition, we conducted semi-structured interviews with
      major directors of each department. The catastrophic damage caused by the
      earthquake attracted rapid and widespread responses from all the departments
      within the County as well as many external organizations. The inputs from the
      central government and other provincial and municipal government authorities,
      external medical teams, voluntary associations, other countries, and
      international organizations played important roles in minimizing the risk to
      survivors and maintaining social order. By formulating emergency plans,
      departments could more effectively fulfill their functions. Additional strategies
      are required to enhance cooperation and coordination between different sectors,
      and to help social organizations and the general public actively contribute so
      that similar disasters can be more effectively dealt with in the future.

PMID- 20029428
TI  - Changing images of violence in Rap music lyrics: 1979-1997.
AB  - Rap music has been at the center of concern about the potential harmful effects
      of violent media on youth social behavior. This article explores the role of
      changing images of violence in rap music lyrics from the 1970s to the 1990s. The
      results indicate that there has been a dramatic and sustained increase in the
      level of violence in rap music. The percentage of songs mentioning violence
      increased from 27 per cent during 1979-1984 to 60 per cent during 1994-1997. In
      addition, portrayals of violence in later songs are viewed in a more positive
      light as shown by their increased association with glamor, wealth, masculinity,
      and personal prowess. Additional analyses revealed that genre, specifically
      gangster rap, is the most powerful predictor of the increased number of violent
      references in songs. The discussion suggests that violence in rap music has
      increased in response to the complex interplay of changing social conditions such
      as the elevated levels of youth violence in the 1980s and changing commercial
      practices within the music industry.

PMID- 20029429
TI  - Commentary: do violent lyrics call forth a violent culture?

PMID- 20029425
TI  - Emerging roles of ATF2 and the dynamic AP1 network in cancer.
AB  - Cooperation among transcription factors is central for their ability to execute
      specific transcriptional programmes. The AP1 complex exemplifies a network of
      transcription factors that function in unison under normal circumstances and
      during the course of tumour development and progression. This Perspective
      summarizes our current understanding of the changes in members of the AP1 complex
      and the role of ATF2 as part of this complex in tumorigenesis.

PMID- 20029430
TI  - Self-rated health and health problems of undocumented immigrant women in the
      Netherlands: a descriptive study.
AB  - In this descriptive study, 100 female undocumented immigrants aged > or =18 years
      were interviewed about their health condition. The objective was to gain insight
      into the health situation and specific health problems of undocumented women.
      Sixty-five per cent of these undocumented women rated their health as 'poor'
      (moderate or bad) and 91 per cent spontaneously mentioned having current health
      problems. When provided with a list of 26 common health problems, subjects
      reported on average 11.1 complaints. Gynaecological and psychological complaints
      were very prevalent, but seldom mentioned spontaneously. Also obstetric problems
      were numerous. Undocumented women may not present important symptoms to
      physicians when they encounter them. We conclude that physicians should actively
      ask about psychological and gynaecological problems in this patient group.
      Special training on the health problems of undocumented female immigrants for
      health providers is recommended.

PMID- 20029431
TI  - Commentary: undocumented women: pushed from poverty and conflict, pulled into
      unjust disparity.

PMID- 20029432
TI  - Interface Carpet and Fabric Company's sustainability efforts: what the company
      does, the crucial role of employees, and the limits of this approach.
AB  - Much has been written touting the environmental achievements of Interface Carpet
      and Fabric Company, but not much has been said about how this firm has
      accomplished it goals, using employee participation. This case study documents
      the importance and benefits of employee participation, employee perceptions of
      the experience, as well as limits to this approach in achieving the goal of
      sustainability.

PMID- 20029433
TI  - Examining gender equity in health policies in a low- (Peru), middle- (Colombia),
      and high- (Canada) income country in the Americas.
AB  - Gender inequities in health prevail in most countries despite ongoing attempts to
      eliminate them. Assessment of gender-sensitive health policies can be used to
      identify country specific progress as well as gaps and issues that need to be
      addressed to meet health equity goals. This study selected and measured the
      existence of gender-sensitive health policies in a low- (Peru), middle-
      (Colombia), and high (Canada)-income country in the Americas. Investigators
      selected 10 of 20 gender-sensitive health policy indicators and found eight to be
      feasible to measure in all three countries, although the wording and scope
      varied. The results from this study inform policy makers and program planners who
      aim to develop, improve, implement, and monitor national gender-sensitive health
      policies. Future studies should assess the implementation of policy indicators
      within countries and assess their performance in increasing gender equity.

PMID- 20029434
TI  - Viewpoint: childhood undernutrition: a failing global priority.
AB  - Undernutrition remains a significant underlying cause of death among children
      worldwide. Although alleviating hunger is part of the first United Nation's
      Millennium Development Goal and a declared global priority, undernutrition
      continues to be prevalent in low-income and middle-income countries throughout
      the world. The authors review the problem and policies and recommend how,
      particularly in this time of global economic difficulties, to improve policies to
      prevent undernutrition. They advocate even greater urgency.

PMID- 20029436
TI  - The national public health institutes of the world--update.

PMID- 20029438
TI  - Prion-like mechanisms in neurodegenerative diseases.
AB  - Many non-infectious neurodegenerative diseases are associated with the
      accumulation of fibrillar proteins. These diseases all exhibit features that are
      reminiscent of those of prionopathies, including phenotypic diversity and the
      propagation of pathology. Furthermore, emerging studies of amyloid-beta, alpha
      synuclein and tau--proteins implicated in common neurodegenerative diseases-
      suggest that they share key biophysical and biochemical characteristics with
      prions. Propagation of protein misfolding in these diseases may therefore occur
      through mechanisms similar to those that underlie prion pathogenesis. If this
      hypothesis is verified in vivo, it will suggest new therapeutic strategies to
      block propagation of protein misfolding throughout the brain.

PMID- 20029440
TI  - Conflict of interest disclosures.

PMID- 20029439
TI  - Chemosensory organs as models of neuronal synapses.
AB  - Neuronal synapses are important microstructures that underlie complex cognitive
      capacities. Recent studies, primarily in Caenorhabditis elegans and Drosophila
      melanogaster, have revealed surprising parallels between these synapses and the
      'chemosensory synapses' that reside at the tips of chemosensory cells that
      respond to environmental stimuli. Similarities in the structures, mechanisms of
      action and specific molecules found at these sites extend to the presynaptic,
      postsynaptic and glial entities composing both synapse types. In this article I
      propose that chemosensory synapses may serve as useful models of neuronal
      synapses, and consider the possibility that the two synapse types derive from a
      common ancestral structure.

PMID- 20029441
TI  - Targeted therapies: Sunitinib versus interferon-alpha in metastatic RCC.
AB  - Motzer and colleagues present updated results from a multicenter, phase III trial
      of sunitinib versus interferon-alpha as first-line treatment for patients with
      metastatic renal-cell carcinoma. The observed improvement in overall survival for
      patients treated with sunitinib further establishes this agent as the reference
      standard for first-line treatment of good-risk and intermediate-risk patients
      with metastatic renal cancer.

PMID- 20029442
TI  - Hematology: ATG and Newton's third law of motion.
AB  - Patients with hematological malignancies have a risk of developing graft-versus
      host disease (GVHD) following allogeneic hematopoietic stem-cell transplantation.
      The addition of ATG to prophylaxis regimens decreases the incidence of GVHD
      without compromising overall survival in these patients.

PMID- 20029443
TI  - Surgery: Future directions in multimodality therapy for NSCLC.
AB  - Patients with stage III non-small-cell lung cancer (nSclc) comprise a
      heterogeneous population; the role of surgical resection in this setting has been
      controversial. Albain and colleagues recently demonstrated that trimodality
      therapy with lobectomy had clinical benefit for patients with pathologic nodal N2
      stage III nSclc. we discuss the trial and its implications for future lung cancer
      therapy.

PMID- 20029444
TI  - Interaction between capecitabine and brivudin in a patient with breast cancer.
AB  - BACKGROUND: A 66-year-old woman with metastatic mammary carcinoma, who was being
      treated with capecitabine, contracted a herpes zoster infection that was treated
      with the antiviral drug brivudin. A drug-drug interaction between brivudin and
      capecitabine caused medullar aplasia, serious toxic effects to the intestinal
      mucous membrane, hand-foot syndrome, onycholysis and dental pigmentation.
      INVESTIGATIONS: Physical examination, blood analysis, blood cultures, chest X
      ray, bone marrow aspiration and biopsy. DIAGNOSIS: Serious adverse event
      secondary to inhibition of dihydropyrimidine dehydrogenase by a drug-drug
      interaction between capecitabine and brivudin. MANAGEMENT: Intravenous hydration,
      imipenem, red blood cell and platelet transfusions, filgrastim, omeprazole, care
      of the mouth and feet, topical anesthetics, systemic analgesics and parenteral
      nutrition.

PMID- 20029445
TI  - Explanations for worsening cancer survival.
AB  - If cancer survival is reported to be worsening over time or inferior compared to
      other countries, politicians and health-care workers may get blamed because
      suboptimal care is presumed to be the cause. Yet, a variety of reasons exist for
      cancer survival statistics to change for the worse, of which deterioration of
      care is only one. Another explanation is that the improved diagnosis of
      premalignant lesions causes survival statistics to reflect only the most
      aggressive cancers-those with the poorest prognosis. In addition, deleterious
      changes in the distribution of prognostic factors and in the distribution of
      sociodemographic characteristics may negatively affect survival proportions. In
      this article, we identify the pitfalls that might be encountered in comparisons
      of published, population-based survival data from different time periods or
      populations.

PMID- 20029446
TI  - Post-transcriptional regulons coordinate the initiation and resolution of
      inflammation.
AB  - Transcriptional control mechanisms chart the course of the inflammatory response
      by synthesizing mRNAs encoding proteins that promote or inhibit inflammation.
      Because these mRNAs can be long-lived, turning off their synthesis does not
      rapidly stop or change the direction of inflammation. Post-transcriptional
      mechanisms that modify mRNA stability and/or translation provide more rapid and
      flexible control of this process and are particularly important in coordinating
      the initiation and resolution of inflammation. Here, I review the surprising
      variety of post-transcriptional control mechanisms that regulate the initiation
      and resolution of inflammation and discuss how these mechanisms are integrated to
      coordinate this essential process.

PMID- 20029447
TI  - Evolution of host innate defence: insights from Caenorhabditis elegans and
      primitive invertebrates.
AB  - The genetically tractable model organism Caenorhabditis elegans was first used to
      model bacterial virulence in vivo a decade ago. Since then, great strides have
      been made in identifying the host response pathways that are involved in its
      defence against infection. Strikingly, C. elegans seems to detect, and respond
      to, infection without the involvement of its homologue of Toll-like receptors, in
      contrast to the well-established role for these proteins in innate immunity in
      mammals. What, therefore, do we know about host defence mechanisms in C. elegans
      and what can they tell us about innate immunity in higher organisms?

PMID- 20029448
TI  - Pairing computation with experimentation: a powerful coupling for understanding T
      cell signalling.
AB  - T cells are activated when extracellular stimuli, such as a ligand binding to the
      T cell receptor, are converted into functional outputs by the T cell signalling
      network. T cell receptor signalling is a highly complex, stochastic and dynamic
      process involving many interacting proteins. This complexity often confounds
      intuition, making it difficult to develop mechanistic principles that underly
      experimental observations. In this Review, we describe how computational
      approaches can partner successfully with biological experimentation to help
      address this challenge, and we illustrate this paradigm by summarizing recent
      work that shows new aspects of the T cell signalling network.

PMID- 20029449
TI  - Early nonischemic oxidative metabolic dysfunction leads to chronic brain atrophy
      in traumatic brain injury.
AB  - Chronic brain atrophy after traumatic brain injury (TBI) is a well-known
      phenomenon, the causes of which are unknown. Early nonischemic reduction in
      oxidative metabolism is regionally associated with chronic brain atrophy after
      TBI. A total of 32 patients with moderate-to-severe TBI prospectively underwent
      positron emission tomography (PET) and volumetric magnetic resonance imaging
      (MRI) within the first week and at 6 months after injury. Regional lobar
      assessments comprised oxidative metabolism and glucose metabolism. Acute MRI
      showed a preponderance of hemorrhagic lesions with few irreversible ischemic
      lesions. Global and regional chronic brain atrophy occurred in all patients by 6
      months, with the temporal and frontal lobes exhibiting the most atrophy compared
      with the occipital lobe. Global and regional reduction in cerebral metabolic rate
      of oxygen (CMRO(2)), cerebral blood flow (CBF), oxygen extraction fraction (OEF),
      and cerebral metabolic rate of glucose were observed. The extent of metabolic
      dysfunction was correlated with the total hemorrhage burden on initial MRI
      (r=0.62, P=0.01). The extent of regional brain atrophy correlated best with
      CMRO(2) and CBF. Lobar values of OEF were not in the ischemic range and did not
      correlate with chronic brain atrophy. Chronic brain atrophy is regionally
      specific and associated with regional reductions in oxidative brain metabolism in
      the absence of irreversible ischemia.

PMID- 20029450
TI  - Agmatine attenuates brain edema through reducing the expression of aquaporin-1
      after cerebral ischemia.
AB  - Brain edema is frequently shown after cerebral ischemia. It is an expansion of
      brain volume because of increasing water content in brain. It causes to increase
      mortality after stroke. Agmatine, formed by the decarboxylation of L-arginine by
      arginine decarboxylase, has been shown to be neuroprotective in trauma and
      ischemia models. The purpose of this study was to investigate the effect of
      agmatine for brain edema in ischemic brain damage and to evaluate the expression
      of aquaporins (AQPs). Results showed that agmatine significantly reduced brain
      swelling volume 22 h after 2 h middle cerebral artery occlusion in mice. Water
      content in brain tissue was clearly decreased 24 h after ischemic injury by
      agmatine treatment. Blood-brain barrier (BBB) disruption was diminished with
      agmatine than without. The expressions of AQPs-1 and -9 were well correlated with
      brain edema as water channels, were significantly decreased by agmatine
      treatment. It can thus be suggested that agmatine could attenuate brain edema by
      limiting BBB disruption and blocking the accumulation of brain water content
      through lessening the expression of AQP-1 after cerebral ischemia.

PMID- 20029451
TI  - Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI
      patients and CCL2-/- mice.
AB  - Cerebral inflammation involves molecular cascades contributing to progressive
      damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2)
      (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage
      recruitment into damaged parenchyma after TBI. This study analyzed the presence
      of CCL2 in human TBI, and further investigated the role of CCL2 in physiological
      and cellular mechanisms of secondary brain damage after TBI. Sustained elevation
      of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for
      10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4
      to 12 h after closed head injury (CHI). Neurological outcome, lesion volume,
      macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine
      network were thus examined in CCL2-deficient (-/-) mice subjected to CHI. We
      found that CCL2-/- mice showed altered production of multiple cytokines acutely
      (2 to 24 h); however, this did not affect lesion size or cell death within the
      first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in
      lesion volume, macrophage accumulation, and astrogliosis were observed in the
      injured cortex and ipsilateral thalamus of CCL2-/- mice, corresponding to
      improved functional recovery as compared with wild-type mice after CHI. Our
      findings confirm the significant role of CCL2 in mediating post-traumatic
      secondary brain damage.

PMID- 20029452
TI  - Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade
      of the 5-HT 2A receptors.
AB  - [(11)C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro
      IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the
      D(1) receptor (R) over the 5-HT(2A) R in vitro, has shown lower selectivity in
      vivo, hampering measurement of D(1) R in the cortex. [(11)C]NNC112 PET and
      intravenous (i.v) ketanserin challenge were used to (1) confirm the previous
      findings of [(11)C]NNC112 in vivo D(1) R selectivity, and (2) develop a feasible
      methodology for imaging cortical D(1) R without contamination by 5-HT(2A) R.
      Seven healthy volunteers underwent [(11)C]NNC112 PET scans at baseline and after
      a 5-HT(2A) R-blocking dose of ketanserin (0.15 mg/kg, i.v.). Percent BP(ND)
      change between the post-ketanserin and baseline scans was calculated.
      Irrespective of the quantification method used, ketanserin pretreatment led to
      significant decrease of BP(ND) in the cortical (approximately 30%) and limbic
      regions (approximately 20%) but not in the striatum, which contains a much lower
      amount of 5-HT(2A) R. Therefore, ketanserin allows D(1) R signal to be detected
      by [(11)C]NNC112 PET without significant 5-HT(2A) R contamination. These data
      confirm the presence of a significant 5-HT(2A) R contribution to cortical
      [(11)C]NNC112 signal, and call for caution in the interpretation of published
      [(11)C]NNC112 PET findings on cortical D(1) R in humans. In the absence of more
      selective ligands, [(11)C]NNC112 PET with ketanserin can be used for cortical
      D(1) R imaging in vivo.

PMID- 20029453
TI  - Restricted pollen flow of Dieffenbachia seguine populations in fragmented and
      continuous tropical forest.
AB  - Habitat fragmentation can change the ecological context of populations, rupturing
      genetic connectivity among them, changing genetic structure, and increasing the
      loss of genetic diversity. We analyzed mating system and pollen structure in two
      population fragments and two continuous forest populations of Dieffenbachia
      seguine (Araceae), an insect-pollinated understory herb in the tropical rain
      forest of Los Tuxtlas, Mexico, using nine allozyme loci. Mating system analysis
      indicated almost complete outcrossing but some inbreeding among the adults.
      Pollen structure analysis indicated highly restricted pollen flow, both within
      and among populations. We showed that the effective pollination neighborhood was
      small in all populations, and slightly (though not significantly) smaller in
      fragments, partially as a consequence of an increase in density of reproductive
      individuals in those fragments. Using assignment analysis, we showed that all
      populations were strongly structured, suggesting that pollen and seed flow across
      the Los Tuxtlas landscape has been spatially restricted, though sufficient to
      maintain connectedness. Forest fragmentation at Los Tuxtlas has (so far) had
      limited impact on pollen dynamics, despite the changing ecological context, with
      reduced pollinator abundance being partially offset by increased flowering
      density in fragments. Continued outcrossing and limited pollen immigration,
      coupled with more extensive seed migration, should maintain genetic connectedness
      in D. seguine, if fragmentation is not further exacerbated by additional
      deforestation.

PMID- 20029456
TI  - Complete mitochondrial DNA sequences provide new insights into the Polynesian
      motif and the peopling of Madagascar.
AB  - More than a decade of mitochondrial DNA (mtDNA) studies have given the
      'Polynesian motif' renowned status as a marker for tracing the late-Holocene
      expansion of Austronesian speaking populations. Despite considerable research on
      the Polynesian motif in Oceania, there has been little equivalent work on the
      western edge of its expansion - leaving major issues unresolved regarding the
      motif's evolutionary history. This has also led to considerable uncertainty
      regarding the settlement of Madagascar. In this study, we assess mtDNA variation
      in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and
      Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian
      motif in Madagascar; two coding region mutations define a Malagasy-specific sub
      branch. This newly defined 'Malagasy motif' occurs at high frequency in all three
      ethnic groups (13-50%), and its phylogenetic position, geographic distribution,
      and estimated age all support a recent origin, but without conclusively
      identifying a specific source region. Nevertheless, the haplotype's limited
      diversity, similar to those of other mtDNA haplogroups found in our Malagasy
      groups, best supports a small number of initial settlers arriving to Madagascar
      through the same migratory process. Finally, the discovery of this lineage
      provides a set of new polymorphic positions to help localize the Austronesian
      ancestors of the Malagasy, as well as uncover the origin and evolution of the
      Polynesian motif itself.

PMID- 20029457
TI  - A gene-based method for detecting gene-gene co-association in a case-control
      association study.
AB  - Association study (especially the genome-wide association study) now has a key
      function in identification and characterization of disease-predisposing genetic
      variant(s), which customarily involve multiple single nucleotide polymorphisms
      (SNPs) in a candidate region or across the genome. Case-control association
      design remains the most popular and a challenging issue in the statistical
      analysis is the optimal use of all information contained in these SNPs. Previous
      approaches often treated gene-gene interaction as deviation from additive genetic
      effects or replaced it with SNP-SNP interaction. However, these approaches are
      limited for their failure of consideration of gene-gene interaction or gene-gene
      co-association at gene level. Although the co-association of the SNPs within a
      candidate gene can be detected by principal component analysis-based logistic
      regression model, the detection of co-association between genes in genome remains
      uncertain. Here, we proposed a canonical correlation-based U statistic (CCU) for
      detecting gene-based gene-gene co-association in the case-control design. We
      explored its type I error rates and power through simulation and analyzed two
      real data sets. By treating gene as a functional unit in analysis, we found that
      CCU was a strong alternative to previous approaches. We discussed the performance
      of CCU as a gene-based gene-gene co-association statistic and the prospect of
      further improvement.

PMID- 20029458
TI  - CASK mutations are frequent in males and cause X-linked nystagmus and variable
      XLMR phenotypes.
AB  - Mutations of the calcium/calmodulin-dependent serine protein kinase (CASK) gene
      have recently been associated with X-linked mental retardation (XLMR) with
      microcephaly, optic atrophy and brainstem and cerebellar hypoplasia, as well as
      with an X-linked syndrome having some FG-like features. Our group has recently
      identified four male probands from 358 probable XLMR families with missense
      mutations (p.Y268H, p.P396S, p.D710G and p.W919R) in the CASK gene. Congenital
      nystagmus, a rare and striking feature, was present in two of these families. We
      screened a further 45 probands with either nystagmus or microcephaly and mental
      retardation (MR), and identified two further mutations, a missense mutation
      (p.Y728C) and a splice mutation (c.2521-2A>T) in two small families with
      nystagmus and MR. Detailed clinical examinations of all six families, including
      an ophthalmological review in four families, were undertaken to further
      characterise the phenotype. We report on the clinical features of 24 individuals,
      mostly male, from six families with CASK mutations. The phenotype was variable,
      ranging from non-syndromic mild MR to severe MR associated with microcephaly and
      dysmorphic facial features. Carrier females were variably affected. Congenital
      nystagmus was found in members of four of the families. Our findings reinforce
      the CASK gene as a relatively frequent cause of XLMR in females and males. We
      further define the phenotypic spectrum and demonstrate that affected males with
      missense mutations or in-frame deletions in CASK are frequently associated with
      congenital nystagmus and XLMR, a striking feature not previously reported.

PMID- 20029459
TI  - Influences on transfer of selected synthetic pyrethroids from treated Formica to
      foods.
AB  - Children's unstructured eating habits and activities may lead to excess dietary
      exposures not traditionally measured by the US Environmental Protection Agency.
      Influence of these activities on transfer of pesticides from treated Formica to
      foods was studied. The objective was to perform simulation experiments using four
      foods (bread, apple slices, bologna, and sugar cookies) exposed to treated
      Formica after varied time intervals between surface contamination and contact (1,
      6, and 24 h) and frequency of contact with and without recontamination.
      Pesticides investigated included permethrin, bifenthrin, cyfluthrin,
      cypermethrin, and deltamethrin. Data will be used as input parameters for
      transfer efficiencies (TEs) within the Children's Dietary Intake Model (CDIM),
      which predicts total dietary exposure of a child. Pesticide transfer from
      surfaces to bologna and apples was more efficient than to bread and cookies. For
      the bread and cookies, all pyrethroids had a TE that ranged from below detectible
      levels to <= 4%. A combined average of 32-64% and 19-43% was transferred to
      bologna and apples, respectively, for the three contact times for all
      pyrethroids. The TEs of the varied time intervals indicated that increased time
      between contamination and contact showed little difference for bologna, bread,
      and cookies, but a significant difference for apples. As long as pesticide levels
      are measureable on surfaces in children's eating environment, it can be concluded
      that transfer of pesticides to foods will take place. Foods' characteristics had
      an important function in the transfer of pesticides when multiple contacts
      occurred. Regardless of recontamination, pesticides were efficiently transferred
      from the treated surface to bologna. The bologna did not reach a saturation point
      during the contacts. Pesticides were also efficiently transferred to apples, but
      reached a maximum TE during the second contact. The distribution of activity
      factors within CDIM needs to reflect the differences in the characteristics of
      the foods.

PMID- 20029460
TI  - Hypoxia induces T-cell apoptosis by inhibiting chemokine C receptor 7 expression:
      the role of adenosine receptor A(2).
AB  - Hypoxia is a major characteristic of the tumor microenvironment, and its effects
      on immune cells are proposed to be important factors for the process of tumor
      immune escape. It has been reported that hypoxia affects the function of
      dendritic cells and the antitumor function of T cells. Here we discuss the
      effects of hypoxia on T-cell survival. Our results showed that hypoxia induced
      apoptosis of T cells. Adenosine and adenosine receptors (AR) are important to the
      hypoxia-related signaling pathway. Using AR agonists and antagonists, we
      demonstrated that hypoxia-induced apoptosis of T cells was mediated by A(2a )and
      A(2b) receptors. Furthermore, we are the first, to our knowledge, to report that
      hypoxia significantly inhibited the expression of chemokine C receptor 7 (CCR7)
      of T cells via the A(2)R signal pathway, perhaps representing a mechanism of
      hypoxia-induced apoptosis of T cells. Collectively, our research demonstrated
      that hypoxia induces T-cell apoptosis by the A(2)R signaling pathway partly by
      suppressing CCR7. Blocking the A(2)R signaling pathway and/or activation of CCR7
      can increase the anti-apoptosis function of T cells and may become a new strategy
      to improve antitumor potential.

PMID- 20029461
TI  - Intracellular signaling mechanisms regulating the activation of human eosinophils
      by the novel Th2 cytokine IL-33: implications for allergic inflammation.
AB  - The novel interleukin (IL)-1 family cytokine IL-33 has been shown to activate T
      helper 2 (Th2) lymphocytes, mast cells and basophils to produce an array of
      proinflammatory cytokines, as well as to mediate blood eosinophilia, IgE
      secretion and hypertrophy of airway epithelium in mice. In the present study, we
      characterized the activation of human eosinophils by IL-33, and investigated the
      underlying intracellular signaling mechanisms. IL-33 markedly enhanced eosinophil
      survival and upregulated cell surface expression of the adhesion molecule
      intercellular adhesion molecule (ICAM)-1 on eosinophils, but it suppressed that
      of ICAM-3 and L-selectin. In addition, IL-33 mediates significant release of the
      proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2. We found that IL
      33-mediated enhancement of survival, induction of adhesion molecules, and release
      of cytokines and chemokines were differentially regulated by activation of the
      nuclear factor (NF)-kappaB, p38 mitogen-activated protein kinase (MAPK) and
      extracellular signal-regulated kinase (ERK) pathways. Furthermore, we compared
      the above IL-33 activities with two structurally and functionally related
      cytokines, IL-1beta and IL-18. IL-1beta, but not IL-18, markedly upregulated cell
      surface expression of ICAM-1. IL-1beta and IL-18 also significantly enhanced
      eosinophil survival, and induced the release of IL-6 and chemokines CXCL8 and
      CCL2 via the activation of the NF-kappaB, p38 MAPK and ERK pathways. Synergistic
      effects on the release of IL-6 were also observed in combined treatment with IL
      1beta, IL-18 and IL-33. Taken together, our findings provide insight into IL-33
      mediated activation of eosinophils via differential intracellular signaling
      cascades in the immunopathogenesis of allergic inflammation.

PMID- 20029463
TI  - Cross-immune tolerance: conception and its potential significance on
      transplantation tolerance.
AB  - The diversity of alloreactive T cells in graft rejection and the presence of
      extensive crossreactivity among alloreactive T cells indicate that the induction
      of transplantation tolerance may fundamentally alter the size of host T-cell
      repertoire involved in protective immunity and immune surveillance, especially
      those that are crossreactive to conventional antigens. We herein highlight the
      crossreactive nature of alloreactive T cells and the potential risks of altered T
      cell repertoire associated with the induction of transplantation tolerance. The
      possibility that T-cell tolerance to one set of antigens results in their
      tolerance to other unrelated antigens due to T-cell crossreactivity and/or
      heterogeneity is defined as 'cross-immune tolerance'. The definition and
      significance of this concept were discussed in details.

PMID- 20029462
TI  - Experimental evidence on the immunopathogenesis of primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease for which
      an autoimmune pathogenesis is supported by clinical and experimental data,
      including the presence of autoantibodies and autoreactive T cells. The etiology
      remains to be determined, yet data suggest that both a susceptible genetic
      background and unknown environmental factors determine disease onset. Multiple
      infectious and chemical candidates have been proposed to trigger the disease in a
      genetically susceptible host, mostly by molecular mimicry. Most recently, several
      murine models have been reported, including genetically determined models as well
      as models induced by immunization with xenobiotics and bacteria.

PMID- 20029464
TI  - IFN-inducible p47 GTPases display differential responses to Schistosoma japonicum
      acute infection.
AB  - Interferon gamma induced GTPase (IGTP) (also named Irgm3) and interferon gamma
      inducible protein 47 (IRG-47) (also named Irgd) are interferon (IFN)-inducible
      p47 GTPases that have been shown to regulate host resistance to intracellular
      pathogens. Little knowledge has been known about the role of p47 GTPases in host
      responses against extracellular pathogens. To investigate possible roles of IGTP
      and IRG-47 in the course of Schistosoma japonicum infection, IGTP and IRG-47
      knockout and wild-type (WT) mice were challenged with cercariae of S. japonicum,
      and host responses were analyzed. At the acute stage of S. japonicum infection,
      mice that lacked IGTP displayed similar parasite burden and pathological damage
      to WT mice. Importantly, S. japonicum-infected IRG-47-deficient mice, in contrast
      to IGTP-deficient mice and WT mice, showed significantly reduced worms and lower
      egg-burden, but intense granulomatous reaction evoked by schistosome eggs in
      peripheral parts of liver lobes. In addition, upregulation of inflammation
      related gene expression was observed in the spleen of IRG-47-deficient mice using
      oligonucleotide microarrays, in which multiple pathways of cytokine-cytokine
      receptor interaction, T-cell receptor signaling, complement, coagulation cascades
      and cell adhesion molecules were highlighted. Taken together, these data suggest
      that IGTP and IRG-47 might have distinct features that were differentially
      required for resistance to S. japonicum.

PMID- 20029465
TI  - Risk adapted combined modality treatment in children with Hodgkin's disease: NCI,
      Cairo.
AB  - OBJECTIVE: The objective of this study is to maximize the chance of cure while
      minimizing surgery, radiotherapy and chemotherapy as much as possible to avoid
      late effects and toxicity of combined modality treatment in children with
      Hodgkin's disease. PATIENTS AND METHODS: One hundred twenty-one (121) children
      under the age of 18 years with a histopathologic diagnosis of Hodgkin's disease
      were enrolled into this study. Patients were stratified according to stage into 3
      risk groups: low (Stages: I, II A), intermediate (Stages: II B, III A) and high
      risk group (Stages: III B, IV). Oral Etoposide was used in this study instead of
      procarbazine in the management of boys with HD to reduce the gonadotoxic effects
      of procarbazine. Two cycles of OPPA for females and E-OPA for males were
      effective induction treatment for children with all stages of HD and stage
      tailored chemotherapy (2, 4, 6 cycles of OPPA, E-OPA/ COPP) was sufficient to
      eradicate occult microfoci. Involved field radiotherapy was given in doses of 30,
      25, 20 Gy, depending on the extent of initial chemotherapy and risk status.
      Staging laparotomy was performed in 30 patients out of the 121 patients, 24 of
      them underwent splenectomy. Patients who received whole neck radiotherapy were
      submitted to thyroid U/S and thyroid hormonal profile. Only 3 adolescent patients
      did semen analysis. RESULTS: The overall and disease-free survival rates at 6
      years were 95.3% and 86.1% (95% CI), respectively (entire group), 96.1% , 92.3%
      (95% CI) for low risk, 96.1% , 80.7% (95% CI) for intermediate risk and 93.3% ,
      80% (95% CI) for high risk patients. During the followup period all patients had
      normal thyroid functions. CONCLUSIONS: In children with HD, only low dose
      involved field radiotherapy with reduced doses is needed,if a risk-dependent
      chemotherapy is given. In this series the strategy of selective laparotomy and
      restrictive splenectomy is very useful in the context of combined modality
      treatment, in which laparotomy was omitted if both abdominal U/S and CT were
      negative.

PMID- 20029466
TI  - Clinical significance of immunophenotypic markers in pediatric T-cell acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Cell-marker profiling has led to conflicting conclusions about its
      prognostic significance in T-ALL. AIM: To investigate the prevalence of the
      expression of CD34, CD10 and myeloid associated antigens (CD13/ CD33) in
      childhood T-ALL and to relate their presence to initial clinical and biologic
      features and early response to therapy. PATIENTS AND METHODS: This study included
      67 consecutive patients with newly diagnosed T-ALL recruited from the Children's
      Cancer Hospital in Egypt during the time period from July 2007 to June 2008.
      Immunophenotypic markers and minimal residual disease (MRD) were studied by five
      color flow cytometry. RESULTS: The frequency of CD34 was 34.9% , CD10 33.3% ,
      while CD13/CD33 was 18.8%. No significant association was encountered between
      CD34, CD10 or myeloid antigen positivity and the presenting clinical features as
      age, sex, TLC and CNS leukemia. Only CD10(+) expression had significant
      association with initial CNS involvement (p=0.039). CD34 and CD13/CD33 expression
      was significantly associated with T-cell maturation stages (p<0.05). No
      relationship was observed for age, TLC, gender, NCI risk or CNS involvement with
      early response to therapy illustrated by BM as well as MRD day 15 and day 42.
      CD34(+), CD13/CD33(+) and early T-cell stage had high MRD levels on day 15 that
      was statistically highly significant (p<0.01), but CD10(+) had statistically
      significant lower MRD level on day 15 (p=0.049). However, only CD34 retained its
      significance at an MRD cut-off level of 0.01%. CONCLUSIONS: CD34, CD10, CD13/CD33
      expression, as well as T-cell maturation stages, may have prognostic significance
      in pediatric T-ALL as they have a significant impact on early clearance of
      leukemic cells detected by MRD day 15.

PMID- 20029467
TI  - ZAP-70 as a possible prognostic factor in childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Zeta-chain-associated protein (ZAP- 70) is a 70kD adaptor protein
      that acts quickly after T cell activation to propagate signal. The role of ZAP-70
      in Tcell function is well established, and in the previous years, this molecule
      was considered to be T-cell specific. More recent data have documented a role of
      ZAP-70 in B cells. Interest in ZAP-70 has grown since it has been shown, through
      gene expression profiling, that it is expressed in a subset of cases of chronic
      lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). PURPOSE: The aim of
      this study was to investigate the expression of ZAP-70 in leukemic blasts of 50
      newly diagnosed patients of B-lineage acute lymphoblastic leukemia (ALL), and to
      assess the correlation between ZAP-70 expression and various prognostic factors
      and outcome. PATIENTS AND METHODS: This study included 50 pediatric patients with
      newly diagnosed B-lineage ALL. They were 28 males (56% ) and 22 females (44% )
      presented to the Pediatric Oncology Department, National Cancer Institute, Cairo
      University, during the period from 2005 to 2007. The age range was 2 to 17 years
      with a mean of 8.58+/-5.8 years and median 8 years. All patients were subjected
      at presentation to a full clinical history and physical examination. Patients
      diagnosed with ALL were enrolled on St. Jude Total XV protocol: standard risk and
      low risk according to results of primary investigation. Immunophenotyping was
      done using monoclonal antibodies which were analyzed on Coulter XL (Panel
      included CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD19, CD22, Cytoplasmic m, anti
      k, anti l, CD13, CD33, anti classII MHC and TdT). Cases were considered ZAP-70
      positive when exhibiting a ZAP/GAPDH (Glyceraldehyde- 3-phosphate dehydrogenase)
      ratio >or= 0.13. RESULTS: The study revealed expression of ZAP-70 in 5/50 cases
      (10% ). There was no statistically significant relation between ZAP-70 expression
      and the following: age, Total Leukocytic Count, hepatomegaly and splenomegaly.
      There was a correlation however between ZAP-70- expression and sex. Four patients
      died of disease progression: one patient with positive ZAP-70 expression and 3
      patients with negative ZAP-70 expression. Fifteen patients (30% ) relapsed after
      achieving complete remission (CR) and 3 patients (6% ) did not achieve CR. Four
      patients of those who relapsed had positive ZAP-70 expression. The 2.5 years DFS
      was 73.1% for negative ZAP-70 cases while it was 20% in positive ZAP-70 cases.
      There was a statistically significant difference between 2.5-year DFS and ZAP-70
      expression (p=0.048). The Overall Survival at 2.5-years for negative ZAP-70 cases
      was 93.3% while it was 80% for positive ZAP-70 cases with p-value =0.27.
      CONCLUSIONS: Our results show that in B-Lineage ALL, ZAP-70 expression correlates
      with a worse DFS and an increased relapse rate. Furthermore, these results raise
      the need of prospective trials to evaluate the possibility of designing new
      compounds targeting this protein.

PMID- 20029468
TI  - Detection of anti-asparaginase antibodies during therapy with E.coli asparaginase
      in children with newly diagnosed acute lymphoblastic leukemia and lymphoma.
AB  - BACKGROUND: Asparaginase is an effective antileukemic agent which is included in
      most front-line protocols for pediatric acute lymphoblastic leukemia (ALL)
      worldwide. Since asparaginase is a bacterial protein, it may induce formation of
      antibodies. The reported frequency of anti-asparaginase antibodies is highly
      variable: antibodies have been reported in as many as 79% of adults and as many
      as 70% of children after intravenous or intramuscular administration of E.coli
      asparaginase. PURPOSE: The aim of this study was to determine if the presence of
      antibodies during induction and continuation phases in newly diagnosed children
      with ALL and lymphoblastic lymphoma during therapy with E.coli asparaginase, had
      any correlation with various factors such as: age, gender, hypersensitivity
      reactions, response to therapy and Event Free Survival (EFS). PATIENTS AND
      METHODS: Between the period from March 2005 to May 2007, sixty-four children who
      attended the Menia outpatient pediatric oncology clinic, or were admitted to the
      inpatient department of the Menia oncology center, were enrolled in the study.
      Forty children had newly diagnosed ALL and 24 had lymphoblastic lymphoma.
      Patients were 48 males (75%) and 16 females (25%) with a male:female ratio 3:1.
      Their ages ranged from 3.5 to 17 years with mean age of 9.6 years. All patients
      received asparaginase therapy according to the St. Jude Total XIII protocol, in a
      dose of 10,000 IU/m(2)/dose, intramuscularly for 6-9 doses during the induction
      phase and another 6-9 doses during continuation phase according to disease
      status. RESULTS: Forty one patients achieved complete remission, 9 had partial
      remission, and 14 were lost to followup at different intervals of treatment.
      Antiasparaginase antibodies were detected in 36 patients (56%) out of 64
      patients, and 37 patients (60%) out of 62 patients who were treated with
      asparaginase at day 8 and day 27 of induction phase respectively. Moreover, 33
      patients (61%) out of 54 patients, and 41 patients (83%) out of 50 patients had
      positive antiasparaginase antibodies at week 10 and week 21 of continuation phase
      respectively. The 2-year EFS of the whole group was 50%. There was no
      statistically significant relation between positivity of antiasparaginase
      antibodies and the following: age, gender, hypersensitivity reaction, response to
      therapy and EFS. CONCLUSIONS: The presence of antiasparaginase antibodies was
      unrelated to age, gender, hypersensitivity reaction, response to therapy and
      event free survival of newly diagnosed children with acute lymphoblastic leukemia
      and lymphoblastic lymphoma.

PMID- 20029469
TI  - Phase II trial of metronomic chemotherapy as salvage therapy for patients with
      metastatic breast cancer.
AB  - AIM OF WORK: To evaluate the efficacy and tolerability of metronomic chemotherapy
      (which is the continuous administration of chemotherapy at relatively low
      minimally toxic doses on a frequent schedule of administration at close regular
      intervals with no prolonged drug-free breaks) in metastatic breast cancer
      patients as salvage therapy. PATIENTS AND METHODS: In this phase II study we
      evaluated the clinical efficacy and tolerability of low dose, oral Methotrexate
      (MTX) and Cyclophosphamide (CTX) in patients with metastatic breast cancer.
      Between January 2004 and December 2005, 42 patients received MTX 2.5mg bid on day
      1 and 2 each week and CTX 50mg/day administered continuously. RESULTS: Forty two
      patients were evaluable. The overall clinical benefit was 31% complete response,
      partial response and stable disease (CR+PR+SD >or=24 weeks), while the overall
      response rate was 16.7% (none of the patients attained CR). Toxicity was
      generally mild. The most common non hematological toxicity was elevation in
      transaminases level, it was reported in 40.4% of patients and was reversible,
      while mild grade 1 or 2 neutropenia was the most common hematological toxicity,
      (28.5% of patients). Median time to response was 3+/-0.18 while progression free
      survival (PFS) among patients with clinical benefit was 10 months (95% CI 6.65
      13.44). CONCLUSIONS: This phase II study shows that, the combination of
      continuously low dose MTX and CTX is an active minimally toxic and significantly
      cost effective regimen for the treatment of metastatic breast cancer patients.

PMID- 20029470
TI  - Curcumin attenuates methotraxate-induced hepatic oxidative damage in rats.
AB  - In the present study, we have addressed the ability of curcumin to suppress MTX
      induced liver damage. Hepatotoxicity was induced by injection of a single dose of
      MTX (20mg/kg I.P.). MTX challenge induced liver damage that was well
      characterized histopathologically and biochemically. MTX increased relative
      liver/body weight ratio. Histologically, MTX produced fatty changes in
      hepatocytes and sinusoidal lining cells, mild necrosis and inflammation.
      Biochemically, the test battery entailed elevated activities of serum ALT and
      AST. Liver activities of superoxide dismutase (SOD), catalase (CAT) and level of
      reduced glutathione (GSH), were notably reduced, while lipid peroxidation,
      expressed as malondialdhyde (MDA) level was significantly increased.
      Administration of curcumin (100mg/kg, I.P.) once daily for 5 consecutive days
      after MTX challenge mitigated the injurious effects of MTX and ameliorated all
      the altered biochemical parameters. These results showed that administration of
      curcumin decreases MTX-induced liver damage probably via regulation of
      oxidant/anti-oxidant balance. In conclusion, the present study indicates that
      curcumin may be of therapeutic benefit against MTX-cytotoxicity.

PMID- 20029471
TI  - T(14;18) is not associated with mixed cryoglobulinemia or with clonal B cell
      expansion in egyptian patients with hepatitis C virus infection.
AB  - BACKGROUND/AIM: The mechanisms of B-cell lymphoproliferative disorders in chronic
      hepatitis C virus (HCV) infection are unclear. An increased prevalence of
      circulating monoclonal B-cells and t(14;18) has been reported. Geographic
      heterogeneity of prevalence of t(14;18) has been shown to exist. We investigated
      the prevalence of t(14;18) and B-cell clonality as possible mechanisms of
      lymphomagenesis in chronic HCV patients, in whom cryoglobulinemia status was
      previously detected. METHODS: A cohort of 111 patients was studied, including 87
      patients with chronic HCV disease (18 cryoglobulinemic and 69 non-
      cryoglobulinemic); 24 HCV-negative, cryoglobulin negative patients with other
      nonimmune chronic liver diseases were enrolled as controls. The t(14;18) and IgH
      rearrangement (as a marker of B-cell clonality) were detected by the polymerase
      chain reaction. RESULTS: t(14;18) was detected in 27.6% of HCV patients and in
      none of the controls. Detection rates were comparable in both cryoglobulin
      positive and negative groups (22.2% and 29% , respectively), p=0.769. IgH
      rearrangement was detected in 39.1% of HCV patients and in none of the controls.
      The cryoglobulin-positive group showed significantly higher prevalence of IgH
      rearrangement compared to the cryoglobulin-negative group (61.1% and 33.3% ,
      respectively), p=0.03, OR=3.13 and 95% CI=1.07-9.17. t(14;18) and monoclonal IgH
      rearrangement detection rates were not associated with each other, p=0.467.
      CONCLUSIONS: t(14;18) is uncommon in HCV-mixed cryogoblulinemia Egyptian
      patients; it does not seem to play a role in HCV-associated MC and
      lymphomagenesis in our geographical area. HCV may play a role in mixed
      cryogoblulinemia and lymphomagenesis, probably by inducing clonal B-cell
      expansions.

PMID- 20029472
TI  - Immunohistochemical expression of topoisomerase II alpha and Her-2/neu in
      prostatic carcinoma and benign prostatic hyperplasia.
AB  - BACKGROUND AND PURPOSE: Topoisomerase II a (Topo II a) and Her-2/neu are two
      important targeted therapeutic molecules. The immunohistochemical expression of
      both of them has not been widely studied in prostatic carcinoma and benign
      prostatic hyperplasia (BPH). The aim of this study was to evaluate the
      immunohistochemical expression of Topo II a and Her-2/neu in prostatic carcinoma
      and BPH and compare the expression patterns of both genes in cases of prostatic
      carcinoma in relation to Gleason score and hormonal status. MATERIAL AND METHODS:
      Paraffin blocks of 30 cases of prostatic carcinoma (categorized by Gleason score
      and hormonal status) and 5 cases of BPH presented to the Department of Pathology,
      Faculty of Medicine, Tanta University during the period from 2005 to 2008 were
      retrieved from the files. The immunohistochemical expression of Topo II a and Her
      2/neu antibodies in the above-mentioned diagnostic categories was investigated
      and compared. The percentage of nuclei staining for Topo II a was
      semiquantitated; overexpression was defined as >or=5% nuclear staining. Her-2/neu
      immunoreactivity was scored from 0 to 3 + depending on membrane staining
      intensity and pattern. RESULTS: The expression of Topo II a varied significantly
      among the different studied groups (p<0.001). Topo II a expression increased
      significantly with increased Gleason score in prostatic carcinoma (p=0.001). Its
      expression in both moderately and poorly differentiated carcinomas was
      significantly higher than in BPH (p=0.005 and 0.002 respectively); however the
      difference between its expression in well-differentiated carcinoma and in BPH was
      statistically insignificant (p=0.171). Her-2/neu expression was higher in
      prostatic carcinoma than in BPH, however the difference did not reach the level
      of statistical significance (p=0.084). Also, the increase in its expression
      within prostatic carcinoma cases with increased Gleason score was statistically
      insignificant (p=0.100). There was a significant correlation between Topo II a
      and Her-2/neu expression (p=0.008, r=0.478). Hormone resistant carcinomas showed
      higher expression of Topo II a and Her- 2/neu than carcinomas with no hormone
      treatment, however, the differences were statistically insignificant (p=0.594 and
      0.667 respectively). CONCLUSIONS: Topo II a expression was significantly higher
      in poorly differentiated and moderately differentiated prostatic carcinoma
      compared to BPH. There was a significant increase in Topo II a expression with
      increased Gleason score. Her-2/neu expression was higher in prostatic carcinoma
      than in BPH, however the difference did not reach the level of statistical
      significance and the increase in its expression with increased Gleason score was
      also statistically insignificant. Topo II a and Her-2/neu were co-expressed
      significantly. Hormone resistant carcinomas showed higher expression of both
      markers, however, the differences were statistically insignificant. The latter
      finding may have important therapeutic implications, however, further large scale
      studies are required for confirmation. KEYWORDS: Topo II a - Her-2/neu -
      Prostatic carcinoma - BPH.

PMID- 20029473
TI  - Time-trend in epidemiological and pathological features of schistosoma-associated
      bladder cancer.
AB  - OBJECTIVE: To investigate the different emerging trends in the features of
      bladder cancer along 17 years. PATIENTS AND METHODS: During a 17-year period
      (1988- 2004), 5071 epithelial bladder cancer patients underwent radical
      cystectomy at the National Cancer Institute (NCI), Cairo University, Egypt. The
      time was divided into 3 time periods to detect changes of the clinicopathologic
      features of patients in these periods. RESULTS: There was a significant
      progressive increase in the patients' age with time and decrease in
      squamous/transitional ratio, with transient increase in male predominance during
      the 2nd time period. Moreover, there was a decrease in the well differentiated
      (grade 1) tumor (p<0.001) and an increase in the frequency of pelvic nodal
      involvement (p<0.001). Transitional cell carcinoma (TCC) patients were
      significantly older than those with squamous cell carcinoma (SCC) (p<0.001).
      Progressive increase of age with time was evident in TCC, SCC and adenocarcinoma
      patients. Male to female ratio changed significantly in TCC and SCC. CONCLUSION:
      Time trend was confirmed with relative decrease in frequency of SCC and increase
      of TCC with changes in their pathological details. The differences between their
      characteristics and that of the Western countries are decreasing.

PMID- 20029474
TI  - Treatment results of adults and children with medulloblastoma NCI, Cairo
      University experience.
AB  - PURPOSE: To evaluate treatment outcome and prognostic factors of adults and
      pediatric medulloblastoma patients treated by adjuvant postoperative craniospinal
      irradiation (CSI) and chemotherapy. PATIENTS AND METHODS: Between 1997 and 2004,
      67 patients were treated in the National cancer Institute- Cairo University; 51
      pediatric patients with a median age of 7 years and 16 adult patients with a
      median age of 25 years. According to the Chang staging system; 50%-35% , 37.5%
      47% and 12.5%-18% had T2, T3 and T4 tumors of adults and pediatric patient's
      population respectively. M1, M2 and M4 were reported in 16% , 3% and in 1.5%
      respectively. All patients underwent primary surgical resection; near total
      resection in 25% , Subtotal resection in 61% ; with tumor residual < 1.5cm(2) in
      49% compared to 51% with > 1.5cm(2) residual tumor and 14% , had biopsy only. All
      patients were treated by craniospinal radiotherapy (RT); with a median dose of
      34Gy to the whole brain, 54Gy to the posterior fossa and 32Gy to the spinal axis.
      The median interval between surgery and RT was 45 days and 38 days for the
      pediatric and adult groups respectively. The median duration of RT was 54 days
      and 52 days for pediatric and adult patients respectively. Thirty four pediatric
      patients (67% ) received concomitant chemotherapy, while 61% received adjuvant
      (postoperative) chemotherapy and 57% received sequential chemotherapy. Only 33%
      of patients did not receive chemotherapy. The median follow-up was 49 months for
      the whole group of patients (range 11-121). RESULTS: For the pediatric and adult
      patients, the 5- and 7-year overall and disease-free survival rates were 89% &
      78% Vs. 84% & 56% and 80% & 68% Vs. 79% & 52% respectively. Fourteen patients
      (21% ) relapsed (10 pediatric and 4 adults) at a median time of 11 months vs. 23
      months and a median follow-up period of 8 and 12 months respectively; Neuro-axis
      was the most common site of relapse (11 patients). Ninety percent (9/10) of the
      pediatric relapses were of the high risk group (8 received no chemotherapy) and
      took place within 2 years; similarly all adult relapses were of the high risk
      group; three relapses took place after 2 years. In univariate analysis, T stages,
      M stages, extent of surgery, CSF seedling and risk category were significant
      prognostic factors for disease free survival for the pediatric age group. At 5
      years, 87% , 87% , 78% , 85% and 85% of T2, M0, near total resection, negative
      CSF seedling and low risk patients were estimated to be disease-free
      respectively, compared to none of the T4, M +, biopsy only, positive CSF seedling
      patients and only 41% of the high risk patients achieved 5 years without
      recurrence (p=0.001, <0.001, <0.001, <0.001, <0.001). Patients who did not
      receive chemotherapy had a 69% 5-year DFS Vs. 76% (p=0.286). For adult patients;
      only the risk category was a significant prognostic factor with 5-year disease
      free survival rate of 100% Vs. 40% for low and high risk respectively (p=0.03).
      On multivaiate analysis only the risk category and the T-stage were significant
      prognostic factors for disease free survival for the pediatric age group (p=0.042
      and 0.031). CONCLUSION: Survival rates of medulloblastoma pediatric patients were
      better than the adult ones. Neuro-axis relapse was the most common site of
      relapse for pediatric patients. Late relapses, lateral tumor location and shorter
      median follow up were noted in adult patients. Advanced tumor stage, metastases
      at presentation, limited tumor resection were powerful prognostic factors among
      the pediatric patients. In addition, high risk category was shown to be a
      prognostic factor for both pediatric and adult patients.

PMID- 20029475
TI  - Long term behavior of pedicled vascularized fibular grafts in reconstruction of
      middle and distal tibia after resection of malignant bone tumors.
AB  - OBJECTIVE: The aim of this study was to evaluate the long term behavior of
      pedicled vascualrized fibula graft in reconstruction of middle and distal tibia
      defects following malignant tumor resection with particular emphasis on success
      in limb salvage and the specific late related complications. PATIENTS AND
      METHODS: Between 1997 and 2006, 16 patients having malignant bone tumors of the
      middle tibia (10 cases) and distal tibia (6 cases) were candidate for wide
      resection of their tumors and reconstruction of the bony defect by ipsilateral
      vascularized pedicled fibular graft based on the peroneal vessels. There were 9
      males and 7 females with a mean age of 13 years at time of surgery (range 11-23
      years). Mean follow up period was 52 months (range 32 -110 months). Fixation was
      done by cast in 14 cases and by plate and screws in 2 patients. According to the
      Enneking staging system (1), 9 patients had stage IIB and 7 had stage IIA. Bony
      union and hypertrophy were assessed radio graphically on regular basis.
      Hypertrophy was estimated in a percentage. Functional limb results were also
      reported according to MSTS functional scores [2]. RESULTS: The mean length of
      bony gap bridged was 14 cm (range of 11.0-16.0 cm) and the mean length of fibula
      harvested was 15.5 cm (range 12-17 cm). Ninety seven percent of patients (15
      cases) healed primarily at a mean time of 4.8 months (range 3.5-6 months).
      Hypertrophy was evident in all patients and ranged from 60 to 210% (mean 91% ).
      Increase in size of the hypertrophied fibula beyond the recipient bone was
      noticed in three cases (18.7% ) and we relate this to weight-bearing forces and
      not to the size of the recipient bone. The mean time of the fibula to double its
      size (10 cases) was 21 months (range 18-31 months). Young patients developed full
      hypertrophy earlier than older patients. Complication rate was low. One patient
      had non union at the proximal end of the fibulotibial junction and two patients
      had stress fracture of the fibula. CONCLUSION: Long term follow-up of pedicled
      vascularized fibula in reconstruction of bony defects of the middle or distal
      tibia after bone tumor resection showed that it is a useful tool in the limb
      salvage procedure. It is a short procedure, inexpensive, with low rate of late
      complications. It has a good outcome regarding the union, hypertrophy and the
      functional outcome.

PMID- 20029476
TI  - Pedicled gastrocnemius flap: clinical application in limb sparing surgical
      resection of sarcoma around the knee region and popliteal fossa.
AB  - OBJECTIVE: To highlight on the versatility of superiorly based pedicled
      gastrocnemius muscle flap in the limb-sparing surgery for bone or soft tissue
      sarcoma around the knee and popliteal fossa. PATIENTS AND METHODS: A total of 30
      patients with localized bone or soft tissue sarcoma around the knee and popliteal
      fossa were treated with limb-salvage procedure. The study included 5 cases with
      bone sarcoma of the distal femur, 15 cases having bone sarcoma of proximal tibia
      and 10 cases having soft tissue sarcoma around the knee region and popliteal
      fossa. Routine preoperative staging studies were done for every patient and
      included local plain radiography, local MRI, isotopic bone scan and CT chest.
      Local MRA or angiography was done in selected cases. According to the Enneking
      staging system, 19 patients had stage IIB and 11 had stage IIA. Patients having
      bone sarcoma of the proximal tibia were subjected to wide resection,
      endoprosthetic reconstruction and reconstruction of the extensor mechanism by the
      medial gastrocnemius muscle flap. Patients having bone sarcoma of the distal
      femur were subjected to wide resection, endo prosthetic reconstruction and
      coverage of the prosthesis and rebalance of the patellar tendon by the medial
      gastrocnemius flap. Patients having soft tissue sarcoma were subjected to wide
      resection and soft tissue coverage with either medial or lateral myocutaneous
      gastrocnemius flap or muscle flap with grafting. Limb function was evaluated
      according to MSTS functional scores. Adjuvant chemotherapy or radiotherapy was
      given according to nationally-agreed protocols. RESULTS: There were 18 males and
      12 females with a mean age of 29 years at the time of surgery (range 11-44
      years). The mean follow-up period was 52 months (range 25-72 months). Resection
      with a negative bony and soft tissue margins could be achieved in all cases. A
      total of 30 flaps were used and included medial gastrocnemius muscle flaps in 21
      cases (15 cases had proximal tibia endoprothesis, 5 cases had distal femur
      endoprothesis, 2 cases had soft tissue sarcoma infiltrating the chin of tibia),
      myocutaneous gastrocnemius flaps in 8 cases having soft tissue sarcoma (5 had
      medial head flap and 3 cases lateral head flap). Flap survival was 100&. The
      success rate of limb salvage was 96.6% with high score functional results
      according to MSTS functional scores. The area of the skin island harvested in
      cases of myocutaneous flaps ranged from 11 to 18cm in length and from 5 to 8cm in
      width and all these cases required grafting of the donor site. Complications
      included partial wound dehiscence in one case, revision of the prosthesis in one
      case, amputation due to local recurrence in one case and significant extension
      lag in 2 cases. CONCLUSION: The unique vascularization of the gastrocnemius
      muscle (one pedicle to each head), the size of the muscle belly, the fact that it
      is situated in the dissection field and that its transfer does not affect the
      function of the spared limb too adversely, makes it particularly suitable for
      limb sparing procedures for sarcoma in the region of the knee and popliteal
      fossa. The medial head is the workhorse muscle flap for soft tissue coverage of
      knee endoprothesis and reconstruction of extensor mechanism. This decreases the
      rate of complications and improves the functional outcome. Reconstruction of the
      soft issue defect improves wound healing, protects exposed deep structures and
      subsequently prevents wound problems, delays adjuvant therapy and secondary
      amputation.

PMID- 20029477
TI  - Canadian guidelines for retinoblastoma care.

PMID- 20029478
TI  - The secret of teaching surgery.

PMID- 20029479
TI  - Is fasting required before cataract surgery?

PMID- 20029481
TI  - Discussing resident participation in cataract surgery.
AB  - OBJECTIVE: To investigate the proportion of patients who would consent to
      resident participation in cataract surgery. STUDY DESIGN: Prospective
      observational case series. PARTICIPANTS: Consecutive series of patients
      presenting for consideration of cataract surgery. METHODS: A specifically worded
      discussion of resident participation in cataract surgery was developed on the
      basis of literature recommendations and was used when obtaining consent for
      cataract surgery from eligible patients. The main outcome measure was the
      proportion of patients who consented to resident participation in their cataract
      surgery. RESULTS: Of the 106 patients eligible for enrollment in the study, 101
      (95.3%) consented to resident participation in their cataract surgery.
      CONCLUSIONS: Despite suggestions in the previous literature to the contrary,
      surgeons can be reassured that the vast majority of patients, when informed by
      means of the wording described in this study, will consent to resident
      participation in their cataract surgery.

PMID- 20029482
TI  - Is fasting required before cataract surgery? A retrospective review.
AB  - OBJECTIVE: To investigate the possibility that fasting is not required before
      cataract surgery. STUDY DESIGN: Retrospective review. PARTICIPANTS: All patients
      who had cataract surgery alone (not combined with corneal or glaucoma surgery) at
      Mount St. Joseph Hospital between April 1, 2007, and March 31, 2008. METHODS:
      Three methods were used to determine whether any cases of aspiration pneumonia
      after cataract surgery had occurred: recall by the supervising anaesthetist, a
      search of hospital medical records for admissions with a diagnosis of pneumonia,
      and recall by the operating surgeons. RESULTS: In 5125 cases of cataract surgery,
      no case of aspiration pneumonia was found. CONCLUSIONS: This study suggests that
      it is safe to perform cataract surgery under topical or infiltration anaesthesia
      with intravenous sedation without fasting prior to surgery.

PMID- 20029483
TI  - Histological and clinical study of eyes with true exfoliation and a double-ring
      sign on the anterior lens capsule.
AB  - OBJECTIVE: To investigate the histological and clinical relation between eyes
      with true exfoliation (TEX) and a double-ring sign (DRS). STUDY DESIGN:
      Retrospective clinical case study. PARTICIPANTS: Twenty-four eyes of 22 patients
      who underwent cataract surgery at Kochi Medical School Hospital and its
      affiliated hospitals during the period from April 1994 to September 2007.
      METHODS: Twenty-four anterior lens capsules excised in cataract surgery underwent
      a histological examination and their clinical backgrounds were investigated. The
      TEX group consisted of 13 eyes with capsular delamination on the anterior lens
      capsule confirmed by slit-lamp microscopy before the surgery, and the DRS group
      consisted of 11 eyes that showed a double-ring sign during capsulorrhexis.
      RESULTS: Twenty-two eyes underwent phacoemulsification and aspiration after
      uneventful capsulorrhexis. Two eyes that showed phacodonesis underwent
      extracapsular cataract extraction. In all specimens the capsular delamination was
      confirmed. In some specimens from both groups, vesicle spaces were observed in
      the capsule and the underlying epithelium. In the TEX group, 8 eyes had capsular
      complications, such as pseudoexfoliation and phacodonesis, and in the DRS group,
      2 eyes had phacodonesis (p = 0.016, student's t test). CONCLUSIONS: In spite of
      different clinical processes leading to capsular delamination, there were not any
      specific histological differences distinguishing the TEX group from the DRS
      group. The incidence of capsular complications was significantly higher in the
      TEX group than in the DRS group.

PMID- 20029484
TI  - Effect of cefuroxime and moxifloxacin on Staphylococcus epidermidis adherence to
      intraocular lenses.
AB  - OBJECTIVE: To investigate and compare the effect of cefuroxime and moxifloxacin
      on adhesion of Staphylococcus epidermidis to intraocular lenses (IOLs). DESIGN:
      Experimental study. METHODS: The 3-pieced hydrophobic acrylic lenses were
      contaminated with S. epidermidis (American Type Culture Collection 35983)
      solutions containing 108 colony-forming units. IOLs were inoculated into test
      tubes containing tryptic soy broth after being held in antibiotic solutions for
      15 minutes. Sonication and vortex procedures were performed in order to remove
      all the remaining bacteria. From each tube 10 microL and 100 microL was taken and
      inoculated into sheep blood agar. The colonies were counted overnight. The
      statistical analyses were made using one-way ANOVA, Turkey Honestly Significant
      Differences test (HSD) and independent t tests, and a p value less than 0.05 was
      considered statistically significant. RESULTS: Overall, the mean numbers of
      colony-forming units on the lenses that were held in control, cefuroxime,
      moxifloxacin 0.5 mg/0.1 mL and moxifloxacin 0.1 mg/0.1 mL solutions were 1398 (SE
      10.01 x 10(3)), 29.9 (SE 1.16 x 10(3)), 0.23 (SD 0.04 x 10(3)), and 0.41 (SD 0.05
      x 10(3)), respectively. The evaluation using one-way ANOVA and Turkey HSD tests
      revealed significant statistical differences among the groups (p = 0.000). The
      evaluation using independent t tests revealed significant statistical differences
      between the 2 moxifloxacin groups (p < 0.05). CONCLUSION: Our results suggest
      that moxifloxacin and cefuroxime significantly inhibit bacterial adherence to
      IOLs. The effect of moxifloxacin on inhibition of bacterial adherence was
      significantly greater than that of cefuroxime. For this reason moxifloxacin might
      be considered as a better prophylactic agent.

PMID- 20029485
TI  - Dehiscence of levator aponeurosis in ptosis after sub-Tenon injection of
      triamcinolone acetonide.
AB  - OBJECTIVE: To report the incidence, intraoperative findings, and surgical outcome
      of secondary ptosis that developed after a sub-Tenon injection of triamcinolone
      acetonide (TA). STUDY DESIGN: Retrospective, cross-sectional study. PARTICIPANTS:
      One hundred forty-seven cases with a total of 286 sub-Tenon TA injections.
      METHODS: The medical records of 163 eyes of 147 cases treated with a sub-Tenon
      injection of 10 mg or 20 mg TA were reviewed. The incidence of secondary ptosis
      (palpebral fissure >2 mm narrower than that of the fellow eye) after a sub-Tenon
      TA injection was determined. The preoperative levator function and margin reflex
      distance (MRD) of the affected eyes, and the intraoperative findings in eyes that
      underwent reconstructive surgery, were evaluated. RESULTS: Eight eyes (5%)
      developed secondary ptosis after the injection and 6 eyes were treated by
      reconstructive surgery. The preoperative levator function of the affected eyes
      did not differ from that of the fellow eyes. Intraoperatively, no septal
      disruption or fat herniation was noted, but an aponeurotic disinsertion was
      identified and repaired with an advancement of the leading edge to the anterior
      tarsal plate. The surgery led to satisfactory results, with improvement of the
      MRD from -1.3 (SD 1.5) mm preoperatively to 2.3 (SD 0.5) mm postoperatively (p =
      0.027). Additional sub-Tenon TA injections were required in 2 eyes after eyelid
      surgery but the ptosis did not worsen. CONCLUSIONS: A sub-Tenon TA injection can
      occasionally cause ptosis by inducing a disinsertion of the levator aponeurosis.
      However, surgical reconstruction can lead to successful resolution of the ptosis.

PMID- 20029486
TI  - The histopathology of involutional ectropion and entropion.
AB  - OBJECTIVE: Involutional ectropion and entropion are characterized by excessive
      horizontal eyelid length, which is thought to be secondary to laxity of the
      medial and lateral canthal tendons and to the stretching of the tarsus.
      Histopathological features of the surgical eyelid specimens from patients with
      involutional ectropion and entropion were evaluated. DESIGN: Prospective
      histopathological study. PARTICIPANTS: Eighteen full-thickness eyelid specimens
      from patients with involutional ectropion and entropion were obtained during
      horizontal eyelid shortening procedures performed at the Ministry of Health
      Ankara Training and Research Hospital. METHODS: All specimens were fixed in 4%
      formaldehyde solution and sectioned sagittally. Hematoxylin-eosin, periodic acid
      Schiff, and Masson's trichrome staining were done for all specimens.
      Histopathologic alterations of the tarsal plate, the palpebral portion of the
      orbicularis muscle, and the conjunctiva were examined. RESULTS: The patients
      ranged in age from 60 to 80 years. The main histopathologic features of the
      ectropic eyelids included collagen degeneration and elastosis of the tarsal
      plate, increased amounts of adipose tissue in the distal tarsus, and subacute
      inflammation and epidermalization of the tarsal conjunctiva. Specimens from
      patients with involutional entropion generally had milder degrees of these
      histopathological features. CONCLUSIONS: The causes of the excessive horizontal
      length of the eyelid, which is thought to be secondary to laxity of the medial
      and lateral canthal tendons, may be collagen degeneration and elastosis of the
      tarsal plate and canthal tendons.

PMID- 20029487
TI  - Beyond visual acuity: functional outcome and patient satisfaction following
      treatment for age-related macular degeneration.
AB  - OBJECTIVE: The success of current medical treatments for choroidal neovascular
      membranes secondary to age-related macular degeneration (AMD) has often been
      determined anatomically by change in lesion size and cessation of leakage.
      Measuring the functional success of treatments has most often revolved around
      visual acuity and has seldom encompassed patients' satisfaction with treatment.
      Using additional objective and subjective measures to assess the outcome of
      treatments may provide greater insight into the visual functions that are lost,
      maintained, or improved during the course of treatment. STUDY DESIGN: Cross
      sectional study. PARTICIPANTS: Forty-six patients diagnosed with exudative AMD.
      Participants had received at least 1 photodynamic therapy (PDT) treatment at the
      time of testing (mean 3.0, SD 1.9). METHODS: Objective tests of visual function
      (Snellen, Early Treatment Diabetic Retinopathy Study, Minnesota Low-Vision
      Reading Test, Contrast Sensitivity, Face Acuity) and a subjective questionnaire,
      the Visual Function-14 (VF-14) were administered to all patients. Treating
      ophthalmologists completed a 3-item questionnaire. RESULTS: No objective measures
      of visual function correlated with patient satisfaction or with the
      ophthalmologists' evaluation of treatment success. The VF-14 was not related to
      the ophthalmologists' evaluation of treatment outcome. Similarly, patient
      satisfaction was unrelated to the ophthalmologists' assessment of treatment
      success. A correlation was found between the VF-14 and patient satisfaction, r =
      0.50, p < 0.05. CONCLUSIONS: Objective measures of visual function do not
      necessarily reflect the viewpoint of patients regarding PDT treatment outcome.
      Patients and doctors differ in their interpretation of treatment success and
      patients' overall satisfaction might best be reflected through a visual function
      questionnaire.

PMID- 20029488
TI  - Disparities in awareness and use of low-vision rehabilitation.
AB  - OBJECTIVE: To describe the demographic, visual, health, and psychological
      variables associated with awareness and use of low-vision rehabilitation services
      in Montreal, Que. STUDY DESIGN: Hospital-based cross-sectional study.
      PARTICIPANTS: Four hundred forty-eight patients with best-corrected visual acuity
      worse than 20/70 in their better eye recruited from 4 ophthalmology departments.
      METHODS: Patients answered questions about their awareness and use of low-vision
      services. Visual acuity was recorded and patients answered the Brief Cope and
      Center for Epidemiologic Studies - Depression Scale questionnaires and provided
      information on demographics and health status. Multiple logistic regression was
      used to identify independent predictors of awareness and use of low-vision
      rehabilitation services. RESULTS: A majority of patients in the sample (71%) were
      aware of low-vision rehabilitation. Of those who were aware, 81% reported
      participating in low-vision rehabilitation. Black patients, those whose first
      language was French, those with less severe visual acuity loss, and those who
      reported less acceptance on the Brief Cope questionnaire were less likely to know
      about low-vision services (p < 0.05). Of those who knew about low-vision
      services, those with less severe visual acuity loss were less likely to have
      participated in low-vision services (p < 0.05). CONCLUSIONS: It is important that
      all those who qualify for low-vision rehabilitation services can access them.
      Although the patients in this Montreal area study showed a high rate of awareness
      and use of low-vision rehabilitation, awareness and use could be improved in
      certain demographic populations and in those with less severe vision loss.

PMID- 20029489
TI  - The effect of low-vision simulators on ophthalmology residents' perception of
      quality of life.
AB  - OBJECTIVE: To evaluate the effect of low-vision simulators on daily activities
      performed by ophthalmology residents. DESIGN: Experimental study. PARTICIPANTS:
      Twenty-nine ophthalmology residents. METHODS: Four types of low-vision simulators
      central loss, peripheral loss, hemianopia, and overall blur-were provided to 29
      residents. They wore these simulators while performing daily activities described
      in the Visual Function-14 (VF-14). Their VF-14 scores after the exercises and the
      utility values before and after the exercises were analyzed. RESULTS: After the
      exercises, the residents recorded significantly different utility values in the
      peripheral loss and overall blur groups. The changes in utility values were
      similar for the senior and junior residents. On the basis of the mean VF-14
      scores of the 4 simulators, the residents considered overall blur to be the most
      serious visual impairment and hemianopia to be the least. CONCLUSION:
      Ophthalmology residents tend to underestimate the impact of visual disability on
      patients' quality of life. They can gain a better appreciation of such an impact
      by using low-vision simulators during daily activities.

PMID- 20029490
TI  - Recurrent anterior uveitis after trabeculectomy with mitomycin C.
AB  - OBJECTIVE: To report 4 cases of recurrent anterior uveitis occurring 1-11 months
      after trabeculectomy with mitomycin C. DESIGN: Observational case series.
      PARTICIPANTS: Four patients in whom recurrent uveitis developed after
      trabeculectomy with mitomycin C, followed at Maisonneuve-Rosemont Hospital in
      Montreal, Quebec. METHODS: Retrospective review of the medical records. RESULTS:
      One to 11 months after trabeculectomy with mitomycin C, noninfectious, recurrent
      anterior uveitis developed in 4 patients with no prior history of uveitis.
      Topical and intravitreal corticosteroids were effective in reducing acute
      inflammation, yet 2 patients went on to have chronic anterior uveitis.
      CONCLUSIONS: Recurrent anterior uveitis presenting later than 3 weeks
      postoperatively may be associated with trabeculectomy with mitomycin C. It should
      be included in the differential diagnosis of a nonresolving blebitis.

PMID- 20029491
TI  - A comparison of Scheimpflug imaging simulated and Holladay equivalent keratometry
      values with partial coherence interferometry keratometry measurements in phakic
      eyes.
AB  - OBJECTIVE: To evaluate the interchangeability of a Scheimpflug camera (Pentacam,
      Oculus) and a partial coherence interferometry keratometer (IOLMaster, Zeiss) for
      measures of keratometry and anterior chamber depth (ACD). A particular focus was
      to determine which Pentacam keratometry value best correlates with the IOLMaster
      and if these results can be used interchangeably in clinical practice. STUDY
      DESIGN: Retrospective comparative study using data from the GRMC Vision Centre
      and ImagePlus Laser Eye Centre. PARTICIPANTS: Fifty-two eyes from 27 patients (11
      male, 16 female) of normal general health with no history of ocular disease.
      METHODS: Each eye was assessed by an IOLMaster as part of a complete eye
      examination, and later by the Pentacam, prior to laser in situ keratomileusis
      (LASIK) surgery. RESULTS: The differences in the mean keratometry readings of the
      IOLMaster and those of the simulated and equivalent Pentacam measurements were
      0.35 D and 0.23 D, respectively. The Bland-Altman plots showed 95% limits of
      agreement (LOA) of 0.92 D and 1.68 D for the same parameters. A comparison of ACD
      measurements revealed a 0.03 mm difference in mean measurements with a 95% LOA of
      0.33 mm. CONCLUSIONS: The interdevice variability was significantly lower than
      that reported previously but still warrants caution if the 2 instruments are to
      be used interchangeably. With an appropriate correction for mean differences, the
      Pentacam's simulated keratometry values would be within 0.46 D of the IOLMaster,
      95% of the time. When the Holladay equivalent keratometry values were compared
      with the IOLMaster, a greater interdevice variability was seen.

PMID- 20029492
TI  - Factors that influence intraocular pressure after cataract surgery in primary
      glaucoma.
AB  - OBJECTIVE: We sought to find predictive factors for favourable postoperative
      intraocular pressure (IOP) after cataract surgery in patients with primary open
      angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). STUDY DESIGN:
      Retrospective evaluation of patients who had undergone cataract surgery.
      PARTICIPANTS: Forty-eight patients with POAG and 48 patients with PACG. METHODS:
      Various clinical factors were evaluated retrospectively in 96 patients. All
      patients had undergone standard 2.75-3.5 mm limbal incision cataract surgery.
      Clinical parameters in patients with successful postoperative IOP courses were
      compared with those in unsuccessful patients. Success was defined as an IOP
      between 6 and 21 mm Hg, with fewer antiglaucoma medications needed compared with
      before surgery, and no need of additional glaucoma surgery. RESULTS: In POAG,
      eyes with a highest preoperative IOP of <31 mm Hg or those being treated with <3
      antiglaucoma medications before surgery had a significantly higher probability of
      success. In PACG, the probability of success was significantly higher if the
      highest preoperative IOP was <42 mm Hg, the number of antiglaucoma medications
      before surgery was <3, or the areas of peripheral anterior synechiae were <4
      clock hours. CONCLUSIONS: Primary small-incision cataract surgery using
      phacoemulsification and foldable intraocular lens implantation may be the
      procedure of choice in patients with medically controlled glaucoma and coexisting
      visually significant cataracts, considering the highest preoperative IOP and
      number of antiglaucoma medications in POAG and PACG, and the area of peripheral
      anterior synechiae in PACG.

PMID- 20029494
TI  - Operative time in postoperative endophthalmitis (Incidence of postoperative
      endophthalmitis in a high-volume cataract surgicentre in Canada. Vol. 44[3]).

PMID- 20029495
TI  - Simple surgical manoeuvre for liberating retinal incarceration during 23-gauge
      vitrectomy for retinal detachment: advantage of vitrectomy trocar/cannula
      systems.

PMID- 20029496
TI  - Optic neuropathy and perichiasmal tuberculomas associated with Mycobacterium
      tuberculosis meningitis in pregnancy.

PMID- 20029497
TI  - Bilateral pterygium, symmetrical nodosity of the auricle, and free iris cyst.

PMID- 20029498
TI  - Transient monocular visual loss following administration of topical latanoprost:
      a case report.

PMID- 20029499
TI  - Atopic dermatitis, facial trauma, and cataract surgery.

PMID- 20029500
TI  - Tuberous sclerosis with homonymous hemianopsia.

PMID- 20029501
TI  - Central retinal vein occlusion after nonperforating sclerectomy without
      mitomycin.

PMID- 20029502
TI  - Management of pseudophakic malignant glaucoma and ultrasound biomicroscopic
      features.

PMID- 20029503
TI  - Macular infarction after 23-gauge transconjunctival sutureless vitrectomy and
      subconjunctival gentamicin for macular pucker: a case report.

PMID- 20029506
TI  - Quercetin's effect on cycling efficiency and substrate utilization.
AB  - Previous evidence suggests that quercetin supplementation increases performance
      in humans. We examined the effects of 3 weeks of quercetin supplementation on
      fuel utilization, gross efficiency (GE), and perceived effort during 3 h of
      cycling over 3 successive days. Forty cyclists were randomized into quercetin and
      placebo groups and tested for maximal oxygen consumption (53.2 +/- 1.2 and 54.7
      +/- 1.1 mL.kg(-1).min(-1)). For 3 weeks following maximal oxygen consumption
      testing, subjects supplemented either 1000 mg.day(-1) quercetin or placebo during
      normal training. Following supplementation, subjects cycled at 57% maximum power
      for 3 h, on 3 successive days, using their own bicycles fitted to CompuTrainer
      Pro Model trainers (RacerMate, Seattle, Wash.). Metabolic measurements were taken
      every 30 min for each 3-h ride. Muscle biopsies obtained from the vastus
      lateralis immediately pre-exercise and postexercise on days 1 and 3 were analyzed
      for muscle glycogen content. Power output remained constant for all 3 exercise
      trials, but significant decreases over time were measured for GE, cadence,
      respiratory exchange ratio, blood glucose, and muscle glycogen. Significant
      increases were measured for heart rate and volume of oxygen consumption over
      time. No quercetin treatment effect was observed for any of the outcome measures
      in this study. These data indicate that GE is reduced during an exhausting 3-h
      bout of exercise. However, quercetin did not significantly affect any outcomes in
      these already well-trained subjects.

PMID- 20029507
TI  - The effect of prior heavy exercise on the parameters of the power-duration curve
      for cycle ergometry.
AB  - The tolerable duration (t) of high-intensity cycle ergometry is well
      characterized by a hyperbolic function of power output (P) with an asymptote
      (termed the critical power (CP)) and a curvature constant (denoted W'). The
      purpose of this study was to investigate the effect of prior heavy exercise (W
      up) that specifically engenders an acidosis on CP and W'. Eight healthy subjects
      performed 2 sets of 4 high-intensity square-wave exercise bouts on a bicycle
      ergometer to estimate CP and W', with (W-up) and without (control) prior
      exercise, respectively. Exercise intensities of the 4 main bouts were selected in
      the range of 90% to 135% peak oxygen uptake so as to reach the limit of tolerance
      between approximately 1.5 and 10 min. The W-up bout was preceded by 6 min cycling
      at a work rate halfway between the lactate threshold and peak oxygen uptake (mean
      +/- SD of 153.8 +/- 29.8 W) starting 12 min before the main bout. Blood lactate
      levels ([La]b) just before the main exercise bouts in W-up conditions were
      significantly higher than those of the control (4.7 +/- 1.1 and 1.4 +/- 0.4
      mEq.L(-1), respectively; p < 0.05). However, there were no significant
      differences in end-exercise [La]b. W-up increased significantly the tolerable
      duration at every work rate compared with the control, which was attributable
      exclusively to increased CP (176.5 +/- 34.3 and 168.7 +/- 31.3 W, respectively; p
      < 0.05), without any significant change in W' (11.0 +/- 3.2 and 11.0 +/- 3.1 kJ,
      respectively). It is concluded that the prior heavy exercise improved performance
      mainly because of an enhanced aerobic component of exercise energetics, as
      indicated by a higher CP and lower increment in the [La]b.

PMID- 20029508
TI  - Trunk muscle activation during moderate- and high-intensity running.
AB  - Time constraints are cited as a barrier to regular exercise. If particular
      exercises can achieve multiple training functions, the number of exercises and
      the time needed to achieve a training goal may be decreased. It was the objective
      of this study to compare the extent of trunk muscle electromyographic (EMG)
      activity during running and callisthenic activities. EMG activity of the external
      obliques, lower abdominals (LA), upper lumbar erector spinae (ULES), and
      lumbosacral erector spinae (LSES) was monitored while triathletes and active
      nonrunners ran on a treadmill for 30 min at 60% and 80% of their maximum heart
      rate (HR) reserve, as well as during 30 repetitions of a partial curl-up and 3
      min of a modified Biering-Sorensen back extension exercise. The mean root mean
      square (RMS) amplitude of the EMG signal was monitored over 10-s periods with
      measures normalized to a maximum voluntary contraction rotating curl-up (external
      obliques), hollowing exercise (LA), or back extension (ULES and LSES). A main
      effect for group was that triathletes had greater overall activation of the
      external obliques (p < 0.05), LA (p = 0.01), and LSES (p < 0.05) than did
      nonrunners. Main effects for exercise type showed that the external obliques had
      less EMG activity during 60% and 80% runs, respectively, than with the curl-ups
      (p = 0.001). The back extension exercise provided less ULES (p = 0.009) and LSES
      (p = 0.0001) EMG activity than the 60% and 80% runs, respectively. In conclusion,
      triathletes had greater trunk activation than nonrunners did while running, which
      could have contributed to their better performance. Back-stabilizing muscles can
      be activated more effectively with running than with a prolonged back extension
      activity. Running can be considered as an efficient, multifunctional exercise
      combining cardiovascular and trunk endurance benefits.

PMID- 20029509
TI  - Acute effects of chocolate milk and a commercial recovery beverage on
      postexercise recovery indices and endurance cycling performance.
AB  - To maximize training quality, athletes have sought nutritional supplements that
      optimize recovery. This study compared chocolate milk (CHOC) with a carbohydrate
      replacement beverage (CRB) as a recovery aid after intense exercise, regarding
      performance and muscle damage markers in trained cyclists. Ten regional-level
      cyclists and triathletes (maximal oxygen uptake 55.2 +/- 7.2 mL.kg(-1).min(-1))
      completed a high-intensity intermittent exercise protocol, then 15-18 h later
      performed a performance trial at 85% of maximal oxygen uptake to exhaustion.
      Participants consumed 1.0 g carbohydrate.kg-1.h-1 of a randomly assigned
      isocaloric beverage (CHOC or CRB) after the first high-intensity intermittent
      exercise session. The same protocol was repeated 1 week later with the other
      beverage. A 1-way repeated measures analysis of variance revealed no significant
      difference (p = 0.91) between trials for time to exhaustion at 85% of maximal
      oxygen uptake (CHOC 13 +/- 10.2 min, CRB 13.5 +/- 8.9 min). The change in
      creatine kinase (CK) was significantly (p < 0.05) greater in the CRB trial than
      in the CHOC trial (increase CHOC 27.9 +/- 134.8 U.L(-1), CRB 211.9 +/- 192.5 U.L(
      1)), with differences not significant for CK levels before the second exercise
      session (CHOC 394.8 +/- 166.1 U.L(-1), CRB 489.1 +/- 264.4 U.L(-1)) between the 2
      trials. These findings indicate no difference between CHOC and this commercial
      beverage as potential recovery aids for cyclists between intense workouts.

PMID- 20029510
TI  - Male and female rats with severe protein restriction present delayed wound
      healing.
AB  - Malnutrition remains a significant problem, not only in developing countries, but
      also in the developed world. The aim of this study was to investigate the effects
      of protein restriction on rat excisional cutaneous healing. Male and female rats
      (12 weeks old) were exposed to different degrees of protein restriction (23%, 12%
      (slight restriction), and 0% (severe restriction)) for 12 weeks. On week 9, a
      full-thickness excisional skin lesion was performed, and the lesion area was
      measured to evaluate wound contraction and re-epithelialization. Euthanasia was
      performed after 12 weeks, and the lesion and adjacent skin were removed, fixed in
      formalin, and embedded in paraffin. Sections were stained with hematoxylin-eosin,
      toluidine blue, picro-mallory, and sirius red, and were immunostained for alpha
      smooth muscle actin. Animals (males and females) exposed to severe protein
      restriction (0% protein) presented impairment of wound contraction. Inflammatory
      cells were present in higher amounts in the protein-restricted groups than in the
      23% group. Extracellular matrix was poorly deposited in the severely restricted
      group (0%), but only mildly disturbed in the slightly restricted group (12%).
      Neovascularization was disturbed in both restricted groups. Our study
      demonstrates that animals exposed to slight protein restriction present disturbed
      wound healing, but animals exposed to severe protein restriction present impaired
      wound healing.

PMID- 20029511
TI  - Serum uric acid is associated with metabolic risk factors for cardiovascular
      disease in the Uygur population.
AB  - The prevalence of hyperuricemia is low in Uygurs, who have a high prevalence of
      cardiovascular risk factors such as hypertension, overweight-obesity,
      dyslipidemia, hyperglycemia, and insulin resistance (IR). This study sought to
      investigate the relationships between serum uric acid (UA) and these risk factors
      in this population. A cross-sectional study was conducted in Uygurs (859 males,
      1268 females) aged 20 to 70 years. Demographic data, systolic blood pressure
      (SBP), diastolic blood pressure (DBP), body mass index (BMI), and fasting and
      postprandial blood were obtained, and biological measurements were determined.
      The mean of BMI, SBP, DBP, total cholesterol, high-density lipoprotein
      cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides,
      fasting blood glucose, fasting insulin, and homeostasis model assessment insulin
      resistance index (HOMA-IR), and the prevalence of hypertension, IR,
      hyperglycemia, overweight-obesity, hypercholesteremia, hyper-LDL-c, and
      hypertriglyceridemia increased with UA but the prevalence of hypo-HDL-c decreased
      (p < 0.05). Logistic regression analysis showed that the odds ratios for IR,
      overweight-obesity, hypercholesteremia, hyper-LDL-c, and hypertriglyceridemia
      against the lowest UA group increased but decreased for hypo-HDL-c (p < 0.05).
      The UA in the hypo-HDL-c group was lower than that of the controls; the
      prevalence of hypo-HDL-c in hyperuricemia subjects was lower than in those with
      normal UA (p < 0.05). But the opposite results were observed between overweight
      obesity, hyperglycemia, IR, hypercholesteremia, hypertriglyceridemia, and hyper
      LDL-c and correspondence controls, respectively (p < 0.05). In Uygur, elevated UA
      is associated with overweight-obesity, hypercholesteremia, hyper-LDL-c,
      hypertriglyceridemia, hyperglycemia, and IR. The HDL-c level significantly
      increases with UA, whereas the prevalence of hypo-HDL-c decreases. Further
      studies are needed to clarify why UA is positively correlated to HDL-c.

PMID- 20029512
TI  - Effects of magnesium on exercise performance and plasma glucose and lactate
      concentrations in rats using a novel blood-sampling technique.
AB  - Repeated blood sampling in rodents is often necessary and difficult. Magnesium
      has been touted as an agent for enhancing physical activity. An auto-blood
      sampling device coupled with a microdialysis analyzer was developed to determine
      blood glucose and lactate concentrations in rats subjected to treadmill exercise.
      The effects of magnesium on exercise performance and blood energy metabolism were
      also evaluated. Sprague-Dawley rats fed a magnesium-adequate diet were randomly
      assigned to 2 experimental groups. Exercise performance was evaluated at 3
      treadmill speeds (10, 15, and 20 m.min(-1)) with or without magnesium
      administration (90 mg.kg-1, intraperitoneal) in the first experiment. In the
      other experiment, each rat was fitted with a catheter in the jugular vein for
      collection of blood samples during the treadmill exercise at a speed of 20 m.min(
      1). Exercise performance was significantly higher at the lower speed of 10 m.min(
      1) in the control group. In addition, exercise performance was significantly
      enhanced only at 20 m.min(-1) in the magnesium-sulfate-treated group when
      compared with the control group. Blood samples were collected every 15 min.
      Glucose concentrations increased significantly and then declined immediately
      after completion of the exercise task at 20 m.min-1 in both groups. However,
      glucose concentrations increased immediately after administration of magnesium
      and increased further during exercise when compared with those of the control
      group. Findings from a repeated blood-sampling assay suggest that increased blood
      glucose contributes to enhanced exercise performance by rats injected
      intraperitoneally with magnesium.

PMID- 20029513
TI  - Repeated-sprint ability in professional and amateur soccer players.
AB  - This study investigated the repeated-sprint ability (RSA) physiological responses
      to a standardized, high-intensity, intermittent running test (HIT), maximal
      oxygen uptake (VO(2) (max)) and oxygen uptake (VO(2)) kinetics in male soccer
      players (professional (N = 12) and amateur (N = 11)) of different playing
      standards. The relationships between each of these factors and RSA performance
      were determined. Mean RSA time (RSA(mean)) and RSA decrement were related to the
      physiological responses to HIT (blood lactate concentration ([La(-)]), r = 0.66
      and 0.77; blood bicarbonate concentration ([HCO(3)-]), r = -0.71 and -0.75; and
      blood hydrogen ion concentration ([H(+)]), r = 0.61 and 0.73; all p < 0.05),
      VO(2) (max) (r = -0.45 and -0.65, p < 0.05), and time constant (tau) in VO(2)
      kinetics (r = 0.62 and 0.62, p < 0.05). VO(2) (max) was not different between
      playing standards (58.5 +/- 4.0 vs. 56.3 +/- 4.5 mL.kg(-1).min(-1); p = 0.227);
      however, the professional players demonstrated better RSA(mean) (7.17 +/- 0.09
      vs. 7.41 +/- 0.19 s; p = 0.001), lower [La-] (5.7 +/- 1.5 vs. 8.2 +/- 2.2 mmol.L(
      1); p = 0.004), lower [H+] (46.5 +/- 5.3 vs. 52.2 +/- 3.4 mmol.L(-1); p = 0.007),
      and higher [HCO3-] (20.1 +/- 2.1 vs. 17.7 +/- 1.7 mmol.L(-1); p = 0.006) after
      the HIT, and a shorter in VO2 kinetics (27.2 +/- 3.5 vs. 32.3 +/- 6.0 s; p =
      0.019). These results show that RSA performance, the physiological response to
      the HIT, and differentiate between professional- and amateur-standard soccer
      players. Our results also show that RSA performance is related to VO(2) max, tau,
      and selected physiological responses to a standardized, high-intensity,
      intermittent exercise.

PMID- 20029514
TI  - Effect of extracellular osmolality on metabolism in contracting mammalian
      skeletal muscle in vitro.
AB  - Extensive research has been conducted on hepatocyte metabolism perturbed under
      the influence of anisosmotic stress. However, much less is known about the
      behaviour of skeletal muscle metabolism under similar conditions. After
      establishing a working model to study anisosmotic stress in resting mammalian
      skeletal muscle, the current study tested the hypothesis that hyperosmotic
      (HYPER) stress would lead to increased creatine, lactate, and measured enzyme
      activity, whereas hypo-osmotic (HYPO) stress would lead to decreased metabolites
      and enzyme activity vs. iso-osmotic (ISO) stress post contraction. Rat soleus
      (SOL) and extensor digitorum longus (EDL) were isolated and incubated in an organ
      bath (95% O2, 5% CO2, pH 7.4, 25 degrees C) altered to targeted osmotic
      conditions (ISO, 290 osmol.L(-1); HYPO, 180 osmol.L(-1); HYPER, 400 osmol.L(-1)).
      Muscle samples were flash frozen after 10 min of contraction. Post contraction,
      muscle water content in the SOL HYPO condition was 18% greater than ISO, and
      HYPER had approximately 14% less water content than ISO (p < 0.05). In the HYPO
      condition, EDL had 21% greater water content than ISO, and HYPER had 17% less
      water content than ISO (p < 0.05). SOL HYPO resulted in higher phosphocreatine
      and lower lactate and creatine vs. HYPER (p < 0.05) but there were no differences
      in EDL between HYPO and HYPER. Pyruvate dehydrogenase activity increased in SOL
      HYPER vs. HYPO, whereas glycogen phosphorylase a increased in EDL HYPER vs. HYPO.
      In conclusion, fibre-type-specific responses exist after contraction such that
      when SOL muscle is perturbed in HYPER, as compared with HYPO, media, metabolic
      activity increases. Future work should focus on glucose uptake-regulation during
      anisosmotic conditions.

PMID- 20029515
TI  - Moderate and heavy oxygen uptake kinetics in postmenopausal women.
AB  - The lack of estrogen in postmenopausal women not using hormone replacement
      therapy (HRT), compared with those using HRT, may reduce submaximal blood flow
      during exercise and result in an oxygen delivery limitation constraining oxygen
      uptake (VO(2) have been changed to V in the abstract, but will appear correctly
      in the body of the paper.) kinetics. The adaptation of pulmonary VO(2) (VO(2p))
      during the transition to exercise in older women was examined in this study.
      Thirty-one healthy postmenopausal women (mean age, 61 +/- 6 years), 15 not using
      HRT and 16 using HRT, performed repeated exercise transitions (6 min) on a cycle,
      to work rates corresponding to 80% of estimated ventilatory threshold (moderate
      intensity exercise) and to Delta50 (heavy-intensity exercise). There was no
      difference in moderate-intensity tauVO(2p) between non-HRT (40 +/- 9 s) and HRT
      (41 +/- 9 s) women. Similarly, there was no difference in heavy-intensity
      tauVO(2p) between non-HRT (44 +/- 8 s) and HRT (45 +/- 8 s) women. Thus, HRT did
      not affect the slowing of VO(2) kinetics of older women.

PMID- 20029516
TI  - Effects of ingesting a commercial thermogenic product on hemodynamic function and
      energy expenditure at rest in males and females.
AB  - The purpose of this study was to examine the effects of a commercially available
      thermogenic product (TP) on resting energy expenditure (REE) and hemodynamic
      variables in a randomized, double-blind, placebo (PL)-controlled study. Eight
      male (age: 23.0 +/- 3.70 years, weight: 95.77 +/- 16.44 kg, height: 182.4 +/-
      7.87 cm) and 10 female (age: 23.6 +/- 4.81 years, weight: 67.25 +/- 5.74 kg,
      height: 172.42 +/- 10.31 cm) physically active individuals participated in this
      study. Participants reported to the laboratory on a 10-h fast and performed
      baseline testing on REE, heart rate, and blood pressure. Participants were then
      randomly assigned to ingest 3 capsules of either an experimental TP or a vitamin
      E PL. Criterion variables were then measured at 1-, 2-, and 3-h post ingestion.
      Data were analyzed by 2-factor analysis of variance (ANOVA) using SPSS, version
      16.0 (SPSS Inc., Chicago, Ill.). Supplementation of the TP resulted in a
      significant main effect for time (p = 0.040) and for interaction (p < 0.01) in
      REE when compared with PL. Post hoc analysis revealed that there was no
      significant difference (p > 0.05) between groups at baseline, but the TP group
      was significantly higher (p < 0.01) than the PL group at 1-, 2-, and 3-h post,
      with peak values being achieved at 2-h post time point. The TP group also
      experienced an overall increase in REE by 17.3%, 19.6%, and 15.3% at the 1-, 2-,
      and 3-h time points, respectively, over baseline values. Conversely, the PL group
      experienced a reduction in REE by 2.5%, 1.8%, and 0.3% at the same time points
      compared with baseline values. There was no significant change in heart rate,
      systolic blood pressure, or diastolic blood pressure in either group. Taken on a
      daily basis, a TP may increase overall energy expenditure. Caloric expenditure
      significantly increased at all 3 time points in the TP group, whereas the PL
      group experienced no change in energy expenditure.

PMID- 20029517
TI  - Effects of ovariectomy and resistance training on lipid content in skeletal
      muscle, liver, and heart; fat depots; and lipid profile.
AB  - The aim of the present study was to investigate the effects of resistance
      training on skeletal muscle lipid content, liver lipid content, heart lipid
      content, fat depots, and lipid profile in ovariectomized rats. Wistar adult
      female rats were divided into 4 groups (n = 10 per group): sedentary (Sed
      Intact), sedentary ovariectomized (Sed-Ovx), strength trained (ChronicEx-intact),
      and strength trained ovariectomized (ChronicEx-Ovx). A 12-week strength-training
      period was used, during which the animals climbed a 1.1-m vertical ladder with
      weights attached to their tails. The sessions were performed once every 3 days,
      with 4-9 climbs and 8-12 dynamic movements per climb. Ovariectomy increased liver
      lipid content and fat depots, and heart and muscle lipid content. There was an
      increase in the atherogenic index and a negative change in lipid profile because
      of the ovariectomy. Resistance training decreased lipid content in the liver,
      soleus, and tibialis anterior, decreased fat depots (mesenteric and
      retroperitoneal), and changed the lipid profile, independently of ovarian hormone
      status. These results indicate the potential benefits of resistance training as
      an alternative strategy to control the effects of ovariectomy on fat depot, lipid
      profile, and tissue lipid content.

PMID- 20029518
TI  - Slow postmeal walking reduces postprandial glycemia in middle-aged women.
AB  - Postprandial blood glucose concentration is a risk factor for the development of
      cardiovascular diseases and diabetes, even at states well below hyperglycemic
      levels. A previous study has shown that postmeal exercise of moderate intensity
      blunts the blood glucose increase after carbohydrate intake (Hostmark et al.
      Prev. Med. 42(5): 369-371). The objective of the present study was to examine
      whether even postmeal slow walking would have a similar effect. Fourteen healthy
      women aged >50 years participated in 3 experiments in a random crossover design:
      after a carbohydrate-rich meal, either they were seated (control experiment) or
      they performed slow postmeal walking for 15 min (W15) or 40 min (W40). Blood
      glucose concentration was determined prior to the meal (fasting), and at 11 time
      points throughout each experiment. The W15 trial lowered the blood glucose values
      during walking and delayed the peak blood glucose value (p = 0.003). In W40, the
      postmeal blood glucose increase during walking was blunted, the peak glucose
      value was delayed (p = 0.001), and the incremental area under the 2-h blood
      glucose curve (IAUC) was reduced (p = 0.014). There was a negative relationship
      between IAUC and walking time (p = 0.016). The individual reducing effect of
      walking on IAUC correlated strongly with IAUC on the control day (p < 0.001). We
      conclude that even slow postmeal walking can reduce the blood glucose response to
      a carbohydrate-rich meal. The magnitude of this effect seems to be related to the
      duration of walking and to the magnitude of the postprandial blood glucose
      response when resting after a carbohydrate-rich meal.

PMID- 20029519
TI  - Protective effect of resveratrol on formation of membrane protein carbonyls and
      lipid peroxidation in erythrocytes subjected to oxidative stress.
AB  - Many of the biological actions of resveratrol have been attributed to its
      antioxidant properties. In this work, we subjected human erythrocytes to in vitro
      oxidative stress by incubating them with tert-butylhydroperoxide (t-BHP). This
      caused a significant increase in the malondialdehyde (MDA) level and the protein
      carbonyl group content above the basal values. The presence of trans-resveratrol
      at micromolar concentrations in the incubation medium protected the erythrocytes
      from t-BHP-induced oxidative stress, as evidenced by the decrease in the MDA
      level and the protein carbonyl group content. The effect of resveratrol was
      concentration and time-dependent. Our findings help to explain some of the
      beneficial effects of resveratrol.

PMID- 20029521
TI  - The C allele of the AGT Met235Thr polymorphism is associated with power sports
      performance.
AB  - Whether the Met235Thr (rs699) variation in the angiotensinogen (AGT) gene,
      encoding a threonine instead of a methionine in codon 235 of the mature protein,
      is associated with athletic performance remains to be elucidated. We compared the
      genotype and allele frequencies for the AGT Met235Thr variation (rs699) in 119
      nonathletic controls, 100 world-class endurance athletes (professional cyclists,
      Olympic-class runners), and 63 power athletes (top-level jumpers, throwers,
      sprinters). Participants were all males and from the same descent (Caucasian) for
      > or =3 generations. The proportion of the CC genotype was significantly higher
      in the power group (34.9%) than in either the control (16%) or the endurance
      group (16%) (p = 0.008 and p = 0.005, respectively). The odds ratio (95% CI) of
      being a power athlete if the subject has a CC genotype was 1.681 (1.176-2.401),
      compared with the control group. In summary, the C allele of the AGT Met235Thr
      polymorphism might favour power sports performance. Although more research is
      needed, this could be attributed to the higher activity of angiotensin II, a
      skeletal muscle growth factor.

PMID- 20029520
TI  - High-intensity interval training attenuates the exercise-induced increase in
      plasma IL-6 in response to acute exercise.
AB  - This aims of this study were to investigate the effects of carbohydrate
      availability during endurance training on the plasma interleukin (IL)-6, IL-8,
      and tumor necrosis factor (TNF)-alpha response to a subsequent acute bout of high
      intensity interval exercise. Three groups of recreationally active males
      performed 6 weeks of high-intensity interval running. Groups 1 (LOW+GLU) and 2
      (LOW+PLA) trained twice per day, 2 days per week, and consumed a 6.4% glucose or
      placebo solution, respectively, before every second training session and at
      regular intervals throughout exercise. Group 3 (NORM) trained once per day, 4
      days per week, and consumed no beverage during training. Each group performed 50
      min of high-intensity interval running at the same absolute workloads before and
      after training. Muscle glycogen utilization in the gastrocnemius muscle during
      acute exercise was reduced (p < 0.05) in all groups following training, although
      this was not affected by training condition. Plasma IL-6 concentration increased
      (p < 0.05) after acute exercise in all groups before and after training.
      Furthermore, the magnitude of increase was reduced (p < 0.05) following training.
      This training-induced attenuation in plasma IL-6 increase was similar among
      groups. Plasma IL-8 concentration increased (p < 0.05) after acute exercise in
      all groups, although the magnitude of increase was not affected (p > 0.05) by
      training. Acute exercise did not increase (p > 0.05) plasma TNF-alpha when
      undertaken before or after training. Data demonstrate that the exercise-induced
      increase in plasma IL-6 concentration in response to customary exercise is
      attenuated by previous exercise training, and that this attenuation appears to
      occur independent of carbohydrate availability during training.

PMID- 20029523
TI  - Abstracts for the 14th International Conference Biochemistry of Exercise: Muscles
      as Molecular and Metabolic Machines. June 2-4, 2009. Guelph, Ontario, Canada.

PMID- 20029525
TI  - Bacterial populations and metabolites in the feces of free roaming and captive
      grizzly bears.
AB  - Gut physiology, host phylogeny, and diet determine the composition of the
      intestinal microbiota. Grizzly bears (Ursus arctos horribilis) belong to the
      Order Carnivora, yet feed on an omnivorous diet. The role of intestinal
      microflora in grizzly bear digestion has not been investigated. Microbiota and
      microbial activity were analysed from the feces of wild and captive grizzly
      bears. Bacterial composition was determined using culture-dependent and culture
      independent methods. The feces of wild and captive grizzly bears contained log
      9.1 +/- 0.5 and log 9.2 +/- 0.3 gene copies x g(-1), respectively. Facultative
      anaerobes Enterobacteriaceae and enterococci were dominant in wild bear feces.
      Among the strict anaerobes, the Bacteroides-Prevotella-Porphyromonas group was
      most prominent. Enterobacteriaceae were predominant in the feces of captive
      grizzly bears, at log 8.9 +/- 0.5 gene copies x g(-1). Strict anaerobes of the
      Bacteroides-Prevotella-Porphyromonas group and the Clostridium coccoides cluster
      were present at log 6.7 +/- 0.9 and log 6.8 +/- 0.8 gene copies x g(-1),
      respectively. The presence of lactate and short-chain fatty acids (SCFAs)
      verified microbial activity. Total SCFA content and composition was affected by
      diet. SCFA composition in the feces of captive grizzly bears resembled the SCFA
      composition of prey-consuming wild animals. A consistent data set was obtained
      that associated fecal microbiota and metabolites with the distinctive gut
      physiology and diet of grizzly bears.

PMID- 20029526
TI  - An Australian environmental survey reveals moderate Spiroplasma biodiversity:
      characterization of four new serogroups and a continental variant.
AB  - An environmental survey of tabanid host spiroplasma carriage was undertaken at 10
      collection sites in Australia during February 1999. A total of 164 tabanid flies,
      representing 27 species, were collected and sustainable spiroplasma isolations
      were made from 48 of the flies. The morphology of the cultured spiroplasmas, as
      observed in M1D medium under dark-field microscopy, was typical of either (i)
      Apis group spiroplasmas (relatively thick cells (approximately 150 nm) with six
      or more turns) or (ii) chrysopicola-syrphidicola-TAAS-1 clade spiroplasmas
      (narrower, often much shorter cells) serologically related to Spiroplasma
      serogroup VIII. Repetitive serological analyses, involving successive rounds of
      dilution cloning and serological reevaluation, identified one serotype referable
      to the Spiroplasma serogroup VIII strain complex and five putative members of the
      Apis clade. Apis clade placement for these five groups was verified using 16S
      rRNA phylogenetic analyses. Among the Apis clade members, one serotype
      representing 11 isolates was identified as a geographic variant of Spiroplasma
      turonicum. Spiroplasma turonicum (Tab4C) was originally isolated from a tabanid
      Haematopoda sp. in France. The other 34 isolates represented four new serogroups
      (= putative species). The following strains are proposed as representatives of
      the new serogroups: strain GSU5478 (group XXXIX), strain GSU5490 (group XL),
      strain GSU5508 (group XLI), and strain GSU5603 (group XLII). In summary, six
      serogroups were observed from isolations originating from seven distinct sample
      sites in Australia. Surprisingly, the serotype with the greatest geographical
      range (five sites from 16 degrees 48.9'S to 35 degrees 40.0'S) and the greatest
      host diversity (nine species over three genera) was the geographic variant of S.
      turonicum, which had only been reported previously in France.

PMID- 20029527
TI  - Construction of a doramectin producer mutant from an avermectin-overproducing
      industrial strain of Streptomyces avermitilis.
AB  - The avermectin analogue doramectin (CHC-B1), which is produced in mutants that
      have an altered biosynthesis pathway of avermectin, is one of the most effective
      agricultural pesticides and antiparasitics. We report here the construction of a
      bkdF olmA double-deletion mutant lacking one of the branched-chain alpha-keto
      acid dehydrogenase encoding genes (bkdF) and the oligomycin PKS encoding gene
      cluster (olmA) in Streptomyces avermitilis 76-05. We then characterized the
      production of various antibiotics in cultures of the deletion mutant. In a
      fermentation medium supplemented with cyclohexanecarboxylic acid, this double
      mutant produced doramectin and its analogues but no oligomycin. The mutant proved
      to be genetically stable, without any antibiotic resistance markers inserted into
      its chromosome, and could potentially become an industrial doramectin-producing
      strain after further improvement.

PMID- 20029528
TI  - The impact of pond depth and environmental conditions on sunlight inactivation of
      Escherichia coli and enterococci in wastewater in a warm climate.
AB  - Microcosm experiments were carried out under dark and real sunlight conditions in
      Ouagadougou (Burkina Faso) to investigate the survival of faecal indicators
      (Escherichia coli and enterococci) in secondary wastewater. Light damage was
      estimated by loss of bacterial culturability. The results clearly show that
      sunlight has a deleterious effect on the survival of both indicators. The mean
      dark inactivation coefficients for E. coli and enterococci were 0.045 and 0.047
      h(-1), respectively, whereas inactivation coefficients in the shallowest
      microcosm (0.1 m) in illuminated conditions were 0.796 and 0.559 h(-1),
      respectively. No significant effect of pond depth (0.1-0.9 m) on the inactivation
      of both indicators was observed in the dark. However, the effect of depth was
      significant in the microcosms exposed to sunlight, probably because of
      attenuation. In illuminated conditions, enterococci were broadly inactivated more
      rapidly than E. coli (T90 = 26.81 h for E. coli and 15.67 h for enterococci in
      the 0.4 m microcosm). However, E. coli presented greater variability in the
      survival capabilities, suggesting difficulties in interpreting data using only E.
      coli as an indicator. Therefore, the use of both indicators together should be
      advisable for the assessment of effluent quality from waste stabilization ponds
      in the Sahelian region.

PMID- 20029529
TI  - Real-time molecular beacon NASBA for rapid and sensitive detection of norovirus
      GII in clinical samples.
AB  - To improve the sensitivity and efficiency of the real-time nucleic acid sequence
      based amplification (NASBA) assay targeting the open reading frame 1-2 (ORF1
      ORF2) junction of the norovirus (NoV) genome, a selection of clinical samples
      were analyzed. The assay results were compared with those of TaqMan and
      conventional reverse transcription PCR (RT-PCR) and a commercial enzyme-linked
      immunoassay (ELISA) for the specific detection of GII NoV in 96 fecal samples.
      Based on end-point dilution, the two real-time assays had similar sensitivities
      (0.01 particle detectable units), two log10 cycles greater than that of
      conventional RT-PCR. GII NoV was detected in 88.54% of the samples by real-time
      NASBA, in 86.46% by TaqMan RT-PCR, in 81.25% by conventional RT-PCR, and in 65.7%
      by ELISA. The two real-time assays were in agreement for 88.5% of the samples.
      These results demonstrate that real-time NASBA with a molecular beacon probe is
      highly sensitive, accurate, and specific for NoV detection in clinical samples.
      Applying this technique to samples with complex matrix and low viral loads, such
      as food and environmental samples, could be useful for the detection of NoVs and
      will improve the prevention of NoV outbreaks.

PMID- 20029530
TI  - Antimicrobial activity of endophytic fungi associated with Orchidaceae in Brazil.
AB  - The purpose of this study was to examine antimicrobial activity of endophytic
      fungi isolated from the leaves, stems, and roots of 54 species of Orchidaceae
      collected in a Brazilian tropical ecosystem. In total, 382 filamentous fungi and
      13 yeast isolates were obtained and cultured to examine the production of crude
      extracts. Thirty-three percent of the isolates displayed antimicrobial activity
      against at least one target microorganism. The multivariate statistical analyses
      conducted indicate that the extracts of endophytic fungi isolated from leaves of
      terrestrial orchids in semideciduous forest were more active against Escherichia
      coli, whereas extracts of endophytic fungi from roots of rupicolous orchids
      collected in rock fields were more active against Candida krusei and Candida
      albicans. Among the fungi that were screened in the study, 22 isolates held their
      antimicrobial activities after replication and were therefore selected for
      assessment of the minimum inhibitory concentration (MIC), which ranged from 62.5
      to 250 microg/mL and 7.8 to 250 microg/mL against bacteria and fungi,
      respectively. One isolate of Alternaria sp. and one isolate of Fusarium oxysporum
      presented the strongest antibacterial activity. Three Fusarium isolates,
      Epicoccum nigrum, and Sclerostagonospora opuntiae showed the greatest MIC values
      against the pathogenic yeasts. This study is the first survey investigating the
      bioactive potential of endophytic fungi associated with tropical Orchidaceae
      species present in Brazilian ecosystems.

PMID- 20029531
TI  - Anti-inflammatory drugs selectively target sporangium development in Mucor.
AB  - It is known that acetylsalicylic acid, an anti-inflammatory and anti
      mitochondrial drug, targets structure development and functions of yeasts
      depending on elevated levels of mitochondrial activity. Using antibody probes, we
      previously reported that sporangia of Mucor circinelloides also contain increased
      mitochondrial activity, yielding high levels of 3-hydroxyoxylipins. This was,
      however, not found in Mortierella alpina (subgenus Mortierella). In this study we
      report that acetylsalicylic acid (aspirin) also targets sporangium development of
      Mucor circinelloides selectively, while hyphae with lower levels of mitochondrial
      activity are more resistant. Similar results were obtained when the anti
      inflammatory compounds benzoic acid, ibuprofen, indomethacin, and salicylic acid
      were tested. The anti-inflammatory drugs exerted similar effects on this
      dimorphic fungus as found under oxygen-limited conditions. Interestingly,
      sporangium development of Mortierella alpina was found not to be selectively
      targeted by these drugs. Mortierella alpina, which could not exhibit dimorphic
      growth under oxygen-limited conditions, was also more sensitive to the anti
      inflammatory drugs when compared with Mucor circinelloides. These results prompt
      further research to assess the applicability of these antimitochondrial
      antifungals to protect plants and animals against Mucor infections.

PMID- 20029532
TI  - Comparative production of ligninolytic enzymes by Phanerochaete chrysosporium and
      Polyporus sanguineus.
AB  - The aim of the present study was to compare the effect of a wide range of culture
      conditions on production of ligninolytic enzymes by Polyporus sanguineus and
      Phanerochaete chrysosporium. Lignin peroxidase production by P. sanguineus was
      comparable with that of P. chrysosporium, although the culture conditions giving
      the highest yield varied greatly between the two fungi. Highest yield of
      manganese peroxidase by P. sanguineus obtained in 0.5% malt extract medium and
      peptone or malt extract supplemented mineral salts broth could not be surpassed
      by P. chrysosporium in any of the optimization experiments. In addition to lignin
      peroxidase and manganese peroxidase, P. sanguineus also produced laccase, which
      was best expressed in malt extract medium supplemented with sugarcane bagasse.

PMID- 20029533
TI  - Morphology of Salmonella Typhimurium typing phages of the Lilleengen set.
AB  - The Lilleengen scheme for typing Salmonella enterica serovar Typhimurium consists
      of 12 tailed phages. Ten phages are podoviruses and morphologically identical to
      Salmonella phage P22. Two phages are siphoviruses and identical to flagella
      specific phage chi.

PMID- 20029534
TI  - Brain renin-angiotensin-aldosterone system and ventricular remodeling after
      myocardial infarct: a review.
AB  - After a myocardial infarct (MI), a variety of mechanisms contribute to
      progressive cardiac remodeling and dysfunction. Progressive activation of central
      sympathoexcitatory pathways appears to depend on a neuromodulatory pathway,
      involving local production of aldosterone and release of endogenous ouabain-like
      compounds ('ouabain') possibly from magnocellular neurons in the supraoptic and
      paraventricular nuclei. 'Ouabain' may lower the membrane potential of neurons and
      thereby enhance activity of angiotensinergic pathways. These central pathways
      appear to coordinate progressive activation of several peripheral mechanisms such
      as sympathetic tone and circulating and cardiac renin-angiotensin-aldosterone
      system (RAAS). Central blockade of aldosterone production, mineralocorticoid
      receptors, 'ouabain' activity, or AT1 receptors similarly prevents activation of
      these peripheral mechanisms. Cardiac remodeling after MI involves progressive
      left ventricular dilation, fibrosis, and decrease in contractile performance.
      Central blockade of this neuromodulatory pathway causes a marked attenuation of
      the remodeling and dysfunction, presumably by inhibiting increases in (cardiac)
      sympathetic activity and RAAS. At the cellular level, these systems may
      contribute to the cardiac remodeling by activating proinflammatory cytokines and
      cardiac myocyte apoptosis. New therapeutic approaches, specifically preventing
      activation of this brain neuromodulatory pathway, may lead to more optimal and
      specific approaches to the prevention of heart failure after MI.

PMID- 20029535
TI  - Redox regulation of stem cell mobilization.
AB  - A growing body of evidence supports the role of redox signaling in the mechanisms
      of hematopoietic stem cell mobilization and homing. Cytokines and adhesion
      molecules control stem cell mobilization through a redox-regulated process. The
      FoxO-SirT network appears to be intimately involved in redox-regulated stem cell
      homeostasis, whereas the process of stem cell differentiation is regulated by
      redox effector factor-1 (Ref-1) protein. Lack of oxygen (hypoxia), specifically
      controlled hypoxia, can stimulate the growth of the stem cells in their niche,
      and hypoxia-inducible factor (HIF)-1alpha appears to play a significant role in
      their maintenance and homing mechanism.

PMID- 20029536
TI  - Emerging concepts in cardiac matrix biology.
AB  - The cardiac extracellular matrix, far from being merely a static support
      structure for the heart, is now recognized to play central roles in cardiac
      development, morphology, and cell signaling. Recent studies have better shaped
      our understanding of the tremendous complexity of this active and dynamic
      network. By activating intracellular signal cascades, the matrix transduces
      myocardial physical forces into responses by myocytes and fibroblasts, affecting
      their function and behavior. In turn, cardiac fibroblasts and myocytes play
      active roles in remodeling the matrix. Coupled with the ability of the matrix to
      act as a dynamic reservoir for growth factors and cytokines, this interplay
      between the support structure and embedded cells has the potential to exert
      dramatic effects on cardiac structure and function. One of the clearest examples
      of this occurs when cell-matrix interactions are altered inappropriately,
      contributing to pathological fibrosis and heart failure. This review will examine
      some of the recent concepts that have emerged regarding exactly how the cardiac
      matrix mediates these effects, how our collective vision of the matrix has
      changed as a result, and the current state of attempts to pharmacologically treat
      fibrosis.

PMID- 20029538
TI  - Apparent desensitization of the effects of sigma receptor ligand haloperidol in
      isolated rat and guinea pig hearts after chronic treatment.
AB  - The supposed role of cardiac sigma receptors is fine tuning of contractility.
      Sigma receptors affect several ionic channels and hence their signaling is
      reflected by the electrophysiological properties of the heart. Numerous ligands
      of sigma receptors are known to prolong the QT interval and therefore cause a
      variety of arrhythmias, including severe ones. The effects of the prototypical
      sigma ligand haloperidol have been studied extensively in humans as well as in
      various animal models, primarily after acute administration. We examined the
      incidence of arrhythmias, changes in heart rate, and prolongation of QT interval
      in isolated Langendorff-perfused rat and guinea pig hearts after they were
      exposed to nanomolar concentrations of haloperidol. Hearts from both untreated
      (acute) and pretreated (chronic) animals were investigated. While QT prolongation
      and arrhythmias due to haloperidol administration were observed in untreated rat
      and guinea pig hearts, arrhythmias were completely prevented in both species of
      chronically treated animals. In treated guinea pigs, the results were generally
      less convincing. Since the hearts were exposed to nanomolar concentration of
      haloperidol, we conclude that our data may be explained by desensitization of
      sigma receptors.

PMID- 20029537
TI  - Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and
      angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative
      responses in vascular smooth muscle cells.
AB  - Endothelin-1 (ET-1) and angiotensin II (Ang II) are vasoactive peptides believed
      to contribute to the pathogenesis of vascular abnormalities such as hypertension,
      atherosclerosis, hypertrophy, and restenosis. The concept of transactivation of
      growth factor receptors, such as epidermal growth factor receptor (EGFR), in
      triggering vasoactive peptide-induced signaling events has gained much
      recognition during the past several years. We have demonstrated that insulin-like
      growth factor type 1 receptor (IGF-1R) plays a role in transducing the effect of
      H2O2, leading to protein kinase B (PKB) phosphorylation. Since vasoactive
      peptides elicit their responses through generation of reactive oxygen species,
      including H2O2, we investigated whether IGF-1R transactivation plays a similar
      role in ET-1- and Ang II-induced PKB phosphorylation and hypertrophic responses
      in vascular smooth muscle cells (VSMC). AG1024, a specific inhibitor of IGF-1R
      protein tyrosine kinase (PTK), attenuated both ET-1- and Ang II-induced PKB
      phosphorylation in a dose-dependent manner. ET-1 and Ang II treatment also
      induced the phosphorylation of tyrosine residues in the autophosphorylation sites
      of IGF-1R, which were blocked by AG1024. In addition, both ET-1 and Ang II evoked
      tyrosine phosphorylation of c-Src, a nonreceptor PTK, whereas pharmacological
      inhibition of c-Src PTK activity by PP2, a specific inhibitor of Src-family
      tyrosine kinase, significantly reduced PKB phosphorylation as well as tyrosine
      phosphorylation of IGF-1R induced by the 2 vasoactive peptides. Furthermore,
      protein and DNA synthesis enhanced by ET-1 and Ang II were attenuated by AG1024
      and PP2. In conclusion, these data suggest that IGF-1R PTK and c-Src PTK play a
      critical role in mediating PKB phosphorylation as well as hypertrophic and
      proliferative responses induced by ET-1 and Ang II in A10 VSMC.

PMID- 20029539
TI  - Changes in PPAR gene expression and myocardial tolerance to ischaemia: relevance
      to pleiotropic effects of statins.
AB  - Peroxisome proliferator-activated receptors (PPAR), which are key transcriptional
      regulators of lipid metabolism and energy production, have been suggested to play
      an important role in myocardial ischaemia-reperfusion (I/R) injury. Their role in
      cardioprotection, however, is not yet fully elucidated. Statins have shown
      beneficial effects on I/R damage beyond lipid lowering, and some of their
      cardioprotective cholesterol-independent effects may be related to the regulation
      of PPAR. To clarify this issue, we explored a potential link between a response
      to I/R and changes in cardiac PPARalpha protein and gene expression in
      simvastatin-treated normocholesterolaemic rats. After 5 days of treatment with
      simvastatin (10 mg/kg per day, p.o.), Langendorff-perfused hearts were subjected
      to 30 min regional ischaemia (occlusion of the left anterior descending coronary
      artery) or global ischaemia and 2 h reperfusion for the evaluation of the infarct
      size (triphenyltetrazolium chloride and planimetry; as percentage of risk area),
      ischaemic arrhythmias, and postischaemic contractile recovery. Baseline PPARalpha
      mRNA and protein levels were increased by 3-fold and 2-fold, respectively, in
      simvastatin-treated hearts compared with the untreated controls. Simvastatin
      treated hearts exhibited smaller size of infarction (11.5% +/- 0.4% vs. 33.7% +/-
      4% in controls; p < 0.01), improved postischaemic contractile recovery, and lower
      severity of arrhythmias during ischaemia and early reperfusion. Enhanced
      resistance to I/R injury was associated with preservation of mRNA and protein
      levels of PPARalpha in contrast to their marked downregulation in controls. In
      conclusion, statin-induced changes in the expression of PPARalpha may contribute
      to attenuation of myocardial I/R injury and thus suggest the involvement of
      cardioprotective mechanisms independent of inhibition of HMG-CoA reductase.

PMID- 20029540
TI  - Contribution of epidermal growth factor receptor transactivation in angiotensin
      II-induced enhanced expression of Gi protein and proliferation in A10 vascular
      smooth muscle cells.
AB  - We have recently shown that vasoactive peptides such as angiotensin II (Ang II)
      and endothelin-1 (ET-1) increased the expression of G(i) proteins and
      proliferation of A10 vascular smooth muscle cells (VSMC) through MAP kinase / PI3
      kinase pathways. The present study was undertaken to examine the implication of
      growth factor receptor activation in Ang II-induced enhanced expression of G(i)
      proteins and proliferation of A10 VSMC and to further investigate the underlying
      mechanisms responsible for these increases. Cell proliferation was determined by
      [(3)H]thymidine incorporation, and the expression of G(i) proteins and the
      phosphorylation of ERK1/2 and epidermal growth factor receptor (EGFR) was
      determined by Western blotting. Treatment of A10 VSMC with Ang II enhanced the
      expression of Gi proteins, which was attenuated by Ang II AT(1) receptor
      antagonist but not by AT(2) receptor antagonist. The inhibitor of EGFR also
      attenuated the enhanced expression of G(i) proteins induced by Ang II to control
      levels. In addition, Ang II enhanced the phosphorylation of EGFR in A10 VSMC, and
      this was restored to control levels by the EGFR inhibitor and antioxidants.
      Furthermore, Ang II also augmented the proliferation and ERK1/2 phosphorylation
      of A10 VSMC, which were restored to control levels by the EGFR inhibitor. These
      data suggest that the Ang II-induced increase in oxidative stress transactivates
      EGFR, which through MAP kinase signaling may contribute to the enhanced
      expression of G(i) proteins and thereby to the increased proliferation of A10
      VSMC.

PMID- 20029541
TI  - Dual effect of polyphenolic compounds on cardiac Na+/K+-ATPase during development
      and persistence of hypertension in rats.
AB  - The enzyme kinetics of cardiac Na(+)/K(+)-ATPase were used for characterizing the
      ATP- and Na(+)-binding sites after administration of red wine polyphenolic
      compounds (Provinol) during developing and sustained hypertension. Hypertension
      was induced in rats (LN group) by the nitric oxide synthase inhibitor N(G)-nitro
      L-arginine methyl ester (L-NAME, 40 mg*kg(-1)*day(-1)). Provinol (40 mg*kg(
      1)*day(-1)) was applied during developing hypertension (LNPF4 group) and
      sustained hypertension (LNPF7/3 group). Provinol reduced the number of active
      Na(+)/K(+)-ATPase molecules in cardiac tissue, as indicated by decreased V(max)
      values (by 33% in LNPF4 and 26% in LNPF7/3 compared with LN). Concerning
      qualitative properties of the enzyme, Provinol induced different effects on the
      ATP- and Na(+)-binding sites of Na(+)/K(+)-ATPase. The ATP-binding site was
      impaired by Provinol, as indicated by increased K(m) value (by 52% in LNPF4 vs.
      LN), suggesting worsened utilization of substrate by the enzyme. In sustained
      hypertension, however, Provinol had no effect on the ATP-binding site, as
      indicated by unchanged K(m) value (LNPF7/3 vs. LN). On the other hand, the Na(+)
      binding site was protected by Provinol, as suggested by decreased K(Na) value (by
      72% in LNPF4 and 69% in LNPF7/3 vs. LN), indicating an increased affinity of the
      enzyme for sodium. Thus, Provinol appeared to stimulate the extrusion of Na(+)
      from cardiac cells, especially in the physiologically important range of sodium
      concentrations (2-10 mmol*L(-1)), during both developing and sustained
      hypertension.

PMID- 20029542
TI  - Mitochondrial KATP opening confers protection against lethal myocardial injury
      and ischaemia-induced arrhythmias in the rat heart via PI3K/Akt-dependent and 
      independent mechanisms.
AB  - Opening of mitochondrial KATP channels (mitoKATP) has been reported to underlie
      protection against ischaemia-reperfusion injury induced by ischaemic
      preconditioning (I-PC); however, the molecular mechanisms of its antiarrhythmic
      effect have not been fully elucidated. We explored the involvement of
      phosphatidylinositol 3-kinase (PI3K)/Akt in the PC-like effect of mitoKATP opener
      diazoxide with particular regard to its role in protection against ischaemia
      induced arrhythmias. Langendorff-perfused rat hearts were subjected to 30 min LAD
      occlusion with or without a prior 15 min of perfusion with diazoxide (50
      micromol/L) given either alone (D-PC) or in combination with the PI3K/Akt
      inhibitor wortmannin (100 nmol/L). In an additional protocol, ischaemia was
      followed by 2 h reperfusion for infarct size (IS) determination (tetrazolium
      staining). The total number of premature ventricular complexes over the whole
      period of ischaemia, episodes of ventricular tachycardia and its duration were
      significantly lower in the D-PC group than in the non-preconditioned controls
      (158 +/- 20, 2 +/- 0.6 and 4.6 +/- 1.8 s vs. 551 +/- 61, 11 +/- 2 and 42 +/- 8 s,
      respectively; p < 0.05), concomitant with a 62% reduction in the size of
      infarction. Wortmannin modified neither arrhythmogenesis nor IS in the non
      preconditioned hearts. Bracketing of diazoxide with wortmannin did not reverse
      the antiarrhythmic protection, whereas the IS-limiting effect was blunted. The
      results indicate that in contrast with the positive role of PI3K/Akt in
      protection against lethal myocardial injury, its activity is not involved in
      suppression of ischaemia-induced arrhythmias conferred by mitoKATP opening in the
      rat heart.

PMID- 20029543
TI  - Omega-3E treatment regulates matrix metalloproteinases and prevents vascular
      reactivity alterations in diabetic rat aorta.
AB  - It is known that increased generation of oxidants and (or) reduced endogenous
      antioxidant defense mechanisms are associated with the etiology of diabetic
      vascular complications. Although a close correlation exists between increased
      oxidative stress and the activation of matrix metalloproteinases (MMPs), little
      is known about the effect of hyperglycemia on the regulation and contribution of
      MMPs in the vascular system. Therefore, we aimed to examine whether omega-3E (50
      mg/kg per day for 4 weeks), a long-chain (n-3) polyunsaturated fatty acid
      enriched with vitamin E, has a beneficial effect on vascular dysfunction via
      affecting MMPs in streptozotocin-diabetic rat aorta. Omega-3E treatment improved
      the diabetes-induced impairment of phenylephrine-induced contraction and
      isoproterenol-induced relaxation responses of aorta. It also exhibited marked
      protection against diabetes-induced degenerative changes in smooth muscle cell
      morphology. Biochemical data showed that this treatment significantly prevented
      important changes, such as inhibition of MMP-2 and MMP-9 activity, loss of tissue
      inhibitor of matrix metalloproteinase-4 (TIMP-4) protein, increase in tissue
      levels of thiol oxidation, endothelin-1, protein kinase C (PKC), and cAMP
      production, and decrease in tissue level of nitrite. These results indicated that
      omega-3E significantly improved impaired vascular responses and regulated the
      activity of MMPs via preventing oxidative injury. Overall, the data suggest that
      omega-3E ameliorates or prevents vascular reactivity alterations in diabetes.
      Such an observation provides preliminary evidence for omega-3E's potential as a
      therapeutic agent for the prevention of vascular disorders in diabetes.

PMID- 20029544
TI  - Omega-3 fatty acids and atorvastatin affect connexin 43 expression in the aorta
      of hereditary hypertriglyceridemic rats.
AB  - Statins and omega-3 polyunsaturated fatty acids (n-3 PUFA) reduce cardiovascular
      disease incidence during hypertriglyceridemia (HTG). To elucidate possible
      cardioprotective mechanisms, we focused on gap junction protein connexin 43
      (Cx43). Its expression is disturbed during atherogenesis, but little information
      is available on its expression during HTG. Experiments were performed on adult
      male hereditary HTG (hHTG) rats treated with n-3 PUFA (30 mg/day) and
      atorvastatin (0.5 mg/100 g body weight per day) for 2 months. Cx43 expression and
      distribution in the aorta were investigated by using Western blotting and
      immunolabeling, followed by quantitative analysis. Transmission
      electronmicroscopy was used to study ultrastructure of endothelial contact sites.
      In contrast to age-matched Wistar, Cx43 expression in aorta of hHTG rats was
      significantly higher (p < 0.05), and prominent Cx43 immunospots were seen in
      tunica media and less in endothelium of hHTG rats. Changes in Cx43 expression
      were accompanied by local qualitative subcellular alterations of interendothelial
      connections. Treatment of hHTG rats with n-3 PUFA and atorvastatin markedly
      lowered Cx43 expression in aorta and modified connexin distribution in
      endothelium and media (p < 0.05 vs. untreated hHTG). The protective effect of
      treatment of HTG was observed on the structural integrity of the endothelium and
      was readily visible at the molecular level. Results indicate the involvement of
      altered Cx43 expression in vascular pathophysiology during HTG and during HTG
      treatment.

PMID- 20029545
TI  - Calcium signaling-mediated endogenous protection of cell energetics in the
      acutely diabetic myocardium.
AB  - In acute diabetic myocardium, calcium signals propagated by intracellular calcium
      transients participate in the protection of cell energetics via upregulating the
      formation of mitochondrial energy transition pores (ETP). Mechanisms coupling ETP
      formation with an increase in membrane fluidity and a decrease in transmembrane
      potential of the mitochondria are discussed. Our results indicate that the
      amplification of calcium transients in the diabetic heart is associated with an
      increase in their amplitude. Moreover, the signals transferred by calcium
      transients also regulated ETP formation in nondiabetic myocardium. Evidence for
      the indispensable role of calcium in the regulation of transition pore formation
      is provided whereby an exchange of cadmium for calcium ions led to a rapid and
      dramatic decrease in the amount of ETP. Another possible regulatory factor of the
      mitochondrial function may be radical-induced damage to the diabetic heart.
      Nevertheless, our data indicate that radical-induced changes in mitochondria
      predominantly concern the respiratory chain and have no appreciable effect on the
      fluidity of the mitochondrial membranes. The residual mitochondrial production of
      ATP owing to its augmented transfer to the cytosol proved to be adequate to
      preserve sufficient levels of adenine nucleotides in the acute diabetic
      myocardium.

PMID- 20029546
TI  - Vascular responses to nitrite are mediated by xanthine oxidoreductase and
      mitochondrial aldehyde dehydrogenase in the rat.
AB  - Sodium nitrite has been shown to have vasodilator activity in experimental
      animals and in human subjects. However, the mechanism by which nitrite anion is
      converted to vasoactive nitric oxide (NO) is uncertain. It has been hypothesized
      that deoxyhemoglobin, xanthine oxidoreductase, mitochondrial aldehyde
      dehydrogenase, and other heme proteins can reduce nitrite to NO, but studies in
      the literature have not identified the mechanism in the intact rat, and several
      studies report no effect of inhibitors of xanthine oxidoreductase. In the present
      study, the effects of the xanthine oxidoreductase inhibitor allopurinol and the
      mitochondrial aldehyde dehydrogenase inhibitor cyanamide on decreases in mean
      systemic arterial pressure in response to i.v. sodium nitrite administration were
      investigated in the rat. The decreases in mean systemic arterial pressure in
      response to i.v. administration of sodium nitrite were inhibited in a selective
      manner after administration of allopurinol in a dose of 25 mg/kg i.v. A second 25
      mg/kg i.v. dose had no additional inhibitory effect on the response to sodium
      nitrite. The decreases in mean systemic arterial pressure in response to sodium
      nitrite were attenuated by cyanamide and a second 25 mg/kg i.v. dose had no
      additional inhibitory effect. In L-NAME-treated animals, allopurinol attenuated
      responses to sodium nitrite and a subsequent administration of cyanamide had no
      additional effect. When the order of administration of the inhibitors was
      reversed, responses to sodium nitrite were attenuated by administration of
      cyanamide and a subsequent administration of allopurinol had no additional
      inhibitory effect. The results of these studies suggest that nitrite can be
      reduced to vasoactive NO in the systemic vascular bed of the rat by xanthine
      oxidoreductase and mitochondrial aldehyde dehydrogenase and that the 2 pathways
      of nitrite activation act in a parallel manner.

PMID- 20029547
TI  - U74389F, a 21-aminosteroid antioxidant, improves neoendothelial morphology, but
      not neointimal thickening after balloon catheter injury.
AB  - U74389F is a compound in a family of 21-aminosteroids devoid of classical
      glucocorticoid action that inhibit lipid peroxidation. These compounds improve
      neurologic function and tissue survival after head or spinal cord injury.
      Dexamethasone inhibits development of intimal hyperplasia (IH) and improves
      attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon
      catheter injury. We tested the hypothesis that U74389F is protective in a
      catheter-induced endothelial-denuded and arterial injury model. A 4-Fr Fogarty
      balloon (BALL) embolectomy catheter was passed through the thoracic aorta of New
      Zealand White rabbits treated with 15 mg/kg U74389F (LAZ) 2 days before and 1
      week after injury. Animals were killed at 4 weeks after surgical intervention,
      and formation of IH was determined by calculating the intimal/medial ratio (I/M).
      The treatment groups of animals were injured untreated (BALL), injured treated
      (BALL/LAZ), uninjured treated (CONTROL/LAZ), and sham-operated treated
      (SHAM/LAZ). Scanning electron microscopy revealed that after injury lazaroid
      treatment produced an improvement of the neoendothelium (alignment in the
      direction of blood and fewer intercellular gaps) as compared with injured but
      untreated aortas. Relaxation to acetylcholine (NO formation) was impaired in
      aortic rings from catheterized animals; lazaroid treatment improved the
      relaxation to 10-6 mol/L acetylcholine but not to lower concentrations. I/M for
      SHAM/LAZ, BALL, and BALL/LAZ was 0.02 +/- 0.02, 21.6 +/- 1.6, and 17.2 +/- 2.5,
      respectively; BALL vs. BALL/LAZ, p < 0.06. An increased contractile response to
      120 mmol/L KCl was observed after lazaroid treatment. This is the first report of
      lazaroid-mediated improvement in the neoendothelial morphology, improved
      neoendothelial NO generation, and augmented hypopolarizing contractile response,
      but no attenuation in the development of IH.

PMID- 20029548
TI  - Attenuation of ischemia-reperfusion-induced alterations in intracellular Ca2+ in
      cardiomyocytes from hearts treated with N-acetylcysteine and N
      mercaptopropionylglycine.
AB  - This study was undertaken to test whether Ca(2+)-handling abnormalities in
      cardiomyocytes after ischemia-reperfusion (I/R) are prevented by antioxidants
      such as N-acetyl L-cysteine (NAC), which is known to reduce oxidative stress by
      increasing the glutathione redox status, and N-(2-mercaptopropionyl)-glycine
      (MPG), which scavenges both peroxynitrite and hydroxyl radicals. For this
      purpose, isolated rat hearts were subjected to 30 min of global ischemia followed
      by 30 min of reperfusion, and cardiomyocytes were prepared to monitor changes in
      the intracellular concentration of free Ca(2+) ([Ca(2+)](i)). Marked depression
      in the left ventricular developed pressure and elevation in the left ventricular
      end-diastolic pressure in I/R hearts were attenuated by treatment with NAC or
      MPG. Cardiomyocytes obtained from I/R hearts showed an increase in the basal
      level of [Ca(2+)](i) as well as augmentation of the low Na(+)-induced increase in
      [Ca(2+)](i), with no change in the KCl-induced increase in [Ca(2+)](i). These I/R
      induced alterations in Ca(2+) handling by cardiomyocytes were attenuated by
      treatment of hearts with NAC or MPG. Furthermore, reduction in the isoproterenol
      , ATP-, ouabain-, and caffeine-induced increases in [Ca(2+)](i) in cardiomyocytes
      from I/R hearts were limited by treatment with NAC or MPG. The increases in the
      basal [Ca(2+)](i), unlike the KCl-induced increase in [Ca(2+)](i), were fully or
      partially prevented by both NAC and MPG upon exposing cardiomyocytes to hypoxia
      reoxygenation, H(2)O(2), or a mixture of xanthine and xanthine oxidase. These
      results suggest that improvement in cardiac function of I/R hearts treated with
      NAC or MPG was associated with attenuation of changes in Ca(2+) handling by
      cardiomyocytes, and the results support the view that oxidative stress due to
      oxyradical generation and peroxynitrite formation plays an important role in the
      development of intracellular Ca(2+) overload in cardiomyocytes as a consequence
      of I/R injury.

PMID- 20029550
TI  - [We and the "others"].

PMID- 20029551
TI  - [Scientific misconduct and the National Advisory Board on Research Ethics].

PMID- 20029549
TI  - Myocardial Ca2+ handling and cell-to-cell coupling, key factors in prevention of
      sudden cardiac death.
AB  - Using whole-heart preparations, we tested our hypothesis that Ca(2+) handling is
      closely related to cell-to-cell coupling at the gap junctions and that both are
      critical for the development and particularly the termination of ventricular
      fibrillation (VF) and hence the prevention of sudden arrhythmic death.
      Intracellular free calcium concentration ([Ca(2+)](i)), ECG, and left ventricular
      pressure were continuously monitored in isolated guinea pig hearts before and
      during development of low K(+)-induced sustained VF and during its conversion
      into sinus rhythm facilitated by stobadine. We also examined myocardial
      ultrastructure to detect cell-to-cell coupling alterations. We demonstrated that
      VF occurrence was preceded by a 55.9% +/- 6.2% increase in diastolic [Ca(2+)](i),
      which was associated with subcellular alterations indicating Ca(2+) overload of
      the cardiomyocytes and disorders in coupling among the cells. Moreover, VF itself
      further increased [Ca(2+)](i) by 58.2% +/- 3.4% and deteriorated subcellular and
      cell-to-cell coupling abnormalities that were heterogeneously distributed
      throughout the myocardium. In contrast, termination of VF and its conversion into
      sinus rhythm was marked by restoration of basal [Ca(2+)](i), resulting in
      recovery of intercellular coupling linked with synchronous contraction.
      Furthermore, we have shown that hearts exhibiting lower SERCA2a (sarcoplasmic
      reticulum Ca(2+)-ATPase) activity and abnormal intercellular coupling (as in
      older guinea pigs) are more prone to develop Ca(2+) overload associated with cell
      to-cell uncoupling than hearts with higher SERCA2a activity (as in young guinea
      pigs). Consequently, young animals are better able to terminate VF spontaneously.
      These findings indicate the crucial role of Ca(2+) handling in relation to cell
      to-cell coupling in both the occurrence and termination of malignant arrhythmia.

PMID- 20029552
TI  - [Differences in cancer treatment].

PMID- 20029554
TI  - [Survival after breast cancer--differences between Norwegian counties].
AB  - BACKGROUND: A major goal in Norwegian health politics is that all patients should
      have equal access to health services irrespective of where they live. Different
      access to health services may affect prognosis. Breast cancer is the most common
      type of cancer among Norwegian women. In this article we analyse breast cancer
      survival by Norwegian county. MATERIAL AND METHODS: Population-based study
      including all Norwegian women diagnosed with breast cancer between 1985 and 2004.
      Breast cancer survival was analysed by county using Cox proportional hazards
      models. RESULTS: 41,833 women with breast cancer were included in the study.
      After a median follow-up time of 5.8 years, 16,494 (39.4 %) women died; 9953
      (60.3 %) of them of breast cancer. Five-year breast cancer specific survival
      varied from 74.1 to 80.6 % in the different counties. Age-adjusted analyses that
      excluded women invited to mammography screening, showed a 20 % difference in
      breast cancer survival (HR 0.80; 95 %KI 0.72-0.90; p < 0.001) between the
      counties. For women diagnosed with tumours in stage two, the difference was 45 %.
      Treatment varied between counties, but the treatment trends were similar in the
      different counties during the study period. INTERPRETATION: There is a
      significant difference in breast cancer survival between Norwegian counties.
      Possible explanations may be differences in offering of mammography screening,
      diagnostics and treatment.

PMID- 20029553
TI  - [Liver transplantation in Norway through 25 years].
AB  - BACKGROUND: In Norway, liver transplantation has been the treatment of choice for
      irreversible acute and chronic liver failure for 25 years. The aim of this
      article is to present a summary of the results obtained. MATERIAL AND METHODS:
      All liver transplants performed in Norway in the period 25.02.84-31.12.08 have
      been reviewed retrospectively with respect to patient and donor epidemiology,
      survival and recurrence. RESULTS: 651 transplants have been performed in this
      period. The annual number of transplants increased gradually up to the year 2000
      (31), and more steeply afterwards - to 79 in 2008. Also the number of organ
      donations has increased and reached 98 (20 pr. million inh.) in 2008. 5-year
      patient survival was 53 % in the period 1984-1994. In the period 2001-2008, 1
      year survival was 90 % and 5-year survival was 83 %. INTERPRETATION: The gradual
      improvement of results should be interpreted in light of improvements within
      transplant surgery, medicine and anaesthesiology and the increased local
      experience due to the increasing number of transplants performed. The transplant
      centre at Rikshospitalet has developed into being among the largest of its kind
      within the Nordic Countries and the results compare well with the best
      international data.

PMID- 20029555
TI  - [Use of radiotherapy in South-Eastern Norway Regional Health Authority].
AB  - BACKGROUND: The National Cancer Plan (NCP) provided the incentives needed to
      establish a technical infrastructure adequate to meet the medical needs of
      radiotherapy in cancer care. The goal of this study is to evaluate the
      development of radiotherapy in South-Eastern Norway Regional Health Authority (S
      E NRHA) and to compare it with the aims of NCP. MATERIAL AND METHODS: The
      material includes the 86,000 courses of radiotherapy performed in S-E NRHA in the
      period 1985-2008. The data were extracted from existing patient registries and
      include cancer diagnosis and patient demographic information. The number of
      treatment series is coupled with cancer incidence of each county and that in S-E
      NRHA. RESULTS: During the latter half of the 1980s, radiotherapy was only offered
      to 50 % (range 30-60 % in the various counties) of those who needed it. The
      situation had improved in 2007, when this figure was close to 80 %, but there was
      still a significant discrepancy between counties (67-91 %). With respect to the
      medical needs, 10 000 additional courses of radiotherapy should have been
      performed in S-E NRHA in the period 2003-2007. INTERPRETATION: The demonstrated
      insufficient use of radiotherapy and the geographical differences between
      counties are not acceptable. A prerequisite for optimal use of radiotherapy in
      cancer treatment is that the medical professions strengthen their oncological
      competence.

PMID- 20029556
TI  - [Environmental toxins in breast milk].
AB  - BACKGROUND: Breast milk is very important to ensure infants a well-composed and
      safe diet during the first year of life. However, the quality of breast milk
      seems to be affected by an increasing amount of environmental toxins
      (particularly so-called Persistent, Bioaccumulative Toxins [PBTs]). Many concerns
      have been raised about the negative effects this may have on infant health.
      MATERIAL AND METHODS: The article is a review of literature (mainly review
      articles) identified through a non-systematic search in PubMed. RESULTS: The
      concentration of PBTs in breast milk is mainly caused by man's position as the
      terminal link in the nutritional chain. Many breast-fed infants have a daily
      intake of such toxins that exceed limits defined for the population in general.
      Animal studies demonstrate effects on endocrine function and neurotoxicity in the
      offspring, and a number of human studies seem to point in the same direction.
      However the "original" optimal composition of breast milk still seems to protect
      against long-term effects of such toxicity. INTERPRETATION: There is
      international consensus about the need to monitor breast milk for the presence of
      PBTs. Such surveillance will be a good indicator of the population's general
      exposure to these toxins and may also contribute to identifying groups as risk
      who should not breast-feed their children for a long time.

PMID- 20029557
TI  - [Should penicillin be given on an empty stomach?].
AB  - To improve absorption, it is usually recommended that penicillin is given on an
      empty stomach. However, current knowledge on pharmacodynamic and pharmacokinetic
      properties of penicillins does not support this recommendation. It is time to
      leave this advice behind, and rather focus on good compliance and completion of
      the entire treatment cure.

PMID- 20029558
TI  - [A 67-year old man with right arm paresthesias].
AB  - A 63-year-old man was admitted to the emergency room with chest pain. He had
      experienced a painful, tingling sensation in the right arm for the last three
      months, as well as pain in the right scapula. ECG and standard blood samples were
      normal. An X-ray of the thorax showed a mass in the superior sulcus on the right
      side. Further investigation with CT and MRI identified a large tumour, about 6 cm
      in size, with infiltrative growth involving the upper costae. Biopsy revealed a
      non-small cell carcinoma of the lung. The patient underwent a tri-modal treatment
      regimen with induction chemotherapy (two courses of cisplatin and etopside) and
      concomitant radiotherapy (50 Gy in 2 Gy fractions) before a right upper lobectomy
      was performed. 1 year after surgery the patient is alive, with no signs of
      recurrent or metastatic disease. Pancoast tumours are an infrequent subtype of
      lung cancers. Diagnostic delay is not uncommon. The peripheral location of the
      tumour generates symptoms that may easily be attributed to other causes, such as
      those of a musculoskeletal origin. Pre-operative chemo-radiotherapy has showed
      improved survival outcomes compared to pre-operative radiotherapy alone.

PMID- 20029559
TI  - [Rare conditions are rare].

PMID- 20029560
TI  - [Time for retirement of tuberculin tests?].

PMID- 20029561
TI  - [What is bisalbuminemia?].

PMID- 20029562
TI  - [Backwards towards the future].
AB  - Partly owing to disregard for natural and cultural history, theoretical medicine
      has become an insufficient guide for much medical practice. Based on theoretical
      elaborations by G.W.F. Hegels (1770-1831) and Charles Darwin (1809-1882) I
      attempt to demonstrate the relevance of such historical knowledge for the much
      debated field of evidence-based medicine.

PMID- 20029563
TI  - [Those days cooperation was poor].

PMID- 20029564
TI  - [A faculty directed by heads of clinics].

PMID- 20029566
TI  - [Surgical treatment of benign gynecological disorders].

PMID- 20029570
TI  - [Quackery, coriander and mercury].

PMID- 20029572
TI  - [Groundless conclusions from Charlotte Haug].

PMID- 20029573
TI  - [Edgar Allan Poe and the disease which disappeared].

PMID- 20029574
TI  - [Physicians in Hamsun's novels].

PMID- 20029575
TI  - [Art as pedagogical catalyzator].

PMID- 20029576
TI  - ["Surgicalization" of medicine and establishment of a Norwegian medical school in
      1814].
AB  - The medical faculty at the royal Frederik's University (later the University of
      Oslo) was established in 1814 with a combined education of medicine and surgery.
      This made the Norwegian medical education quite unique at the time, and the
      university played a main role in uniting medicine and surgery into one
      profession. In other European countries, medical/surgical education in
      universities emerged later, mainly because academic schools for surgical
      education already existed and because both the medical and surgical elites were
      reluctant to let their professions fuse into a unity. However, from the late 1700
      s, a unified education seemed rational for several reasons. The surgical
      education had become scientific; the medical elites had accepted the surgeons'
      clinical-anatomical approach to disease; and Enlightenment ideas favoured a
      utilitarian education of doctors that could serve the society's need of a more
      practical, i.e. more surgical medicine. These factors became influential in
      Norway at the beginning of the 19th century, when the country's first medical
      education was to be built from scratch. The fact there were more positions for
      surgeons than medical doctors was also important, so a school merely for medical
      subjects other than surgery was not feasible.

PMID- 20029577
TI  - [Establishment of a research school--The Gade Institute 1912-35].
AB  - The Gade institute in Bergen was established in 1912, at the same time as the
      city's new hospital was opened at Haukeland. The aim of the benefactor F. G. Gade
      was that the institution should function as a research institute in addition to
      being the hospital's pathological department and laboratory. The task of leading
      this work was given to a young cancer researcher, Magnus Haaland. He succeeded in
      establishing an effective research school within these institutional settings
      through educating assistants in pathological-anatomic, bacteriological and
      serological themes during a two-year rotational arrangement. The institute
      produced a great number of scientific articles and also several doctoral
      dissertations. A hallmark for this research was its practical orientation; almost
      all the major works were concerned with important epidemic diseases in western
      Norway. A reform of the rotational arrangement and a bitter conflict between
      Haaland and the director of the hospital led to a less fruitful development for
      the institute from 1925 until Haaland's death in 1935.

PMID- 20029578
TI  - [On chlorosis and anaemic girls in the end of the 19th century].
AB  - Towards the end of the 1800 s, chlorosis was a frequently used diagnosis, in
      Norway as well as in America and the rest of Europe. The physiological basis for
      the disease was assumed to be decreased levels of haemoglobin and/or red blood
      cells. Chlorosis was not synonymous with anaemia, but rather a subcategory with a
      vague symptom-based picture associated with female puberty. The different
      opinions on causes of the disease can be divided into three main groups:
      environmental, moral and biological-constitutional. At the time, it was well
      known that iron was an effective treatment. In a cultural critical perspective
      the disease was seen both as a phenomenon of degeneration and as a reaction to
      modern life with its stress and demands. During the first decades of the 1900 s,
      the chlorotic girl disappeared from medical textbooks and articles. The article
      points at medical, biological and dietary improvements as explanations for why
      chlorosis disappeared as a diagnosis, but also considers historical aspects such
      as new cultural norms for femininity, changed laws and an increasing political
      understanding of health's role in society.

PMID- 20029579
TI  - [Physicians, books and medical knowledge in Norway around the year 1700].
AB  - Development of medicine in the early modern period (1500-1800) formed the basis
      for modern medicine, in that iatrochemical and mechanistic perceptions of the
      human body gradually became more influential. Several different medical theories
      prevailed and were tested in parallel, and perceptual changes developed over
      time. Few studies have looked into the knowledge universe that Norwegian doctors
      were part of in this period. I have examined book collections owned by the
      physicians Jacob Woldenberg, Georg Blumenthal and Paul Dons, in order to discern
      how physicians practicing in Norway around 1700 responded to this particular
      situation of "complexity". In general, these book collections covered antique
      medical theories and more recent debates within the medical profession at the
      time. Most of the books are from Germany and the Netherlands, which means the
      three doctors were part of firstly a German and secondly a Dutch medical
      tradition. The article is based on the authors' doctoral thesis about doctors'
      and clergymens' book collections in the period 1650-1750.

PMID- 20029580
TI  - [Harald Froshaug and social psychiatry in Norway].
AB  - Harald Froshaug received training in scientific research by Rolv Gjessing (1887
      1959), who was well known for his research on schizophrenic periodic catatonia.
      The Second World War brought new challenges for psychiatrists, and there was a
      pressing need for new treatment procedures and theories. Harald Froshaug was
      inspired by English and American psychiatry, especially the psychoanalytic
      traditions. When he became head of the ward for women at Dikemark hospital in
      Asker in 1949, time was ripe to put new theories and methods into practice.

PMID- 20029581
TI  - [When the knowledge on alloimmune antibody formation came about].

PMID- 20029583
TI  - [The cholera epidemic which came to an end at last].

PMID- 20029584
TI  - [Hope about a HIV vaccine].

PMID- 20029585
TI  - Computer generated hologram from point cloud using graphics processor.
AB  - Computer generated holography is an extremely demanding and complex task when it
      comes to providing realistic reconstructions with full parallax, occlusion, and
      shadowing. We present an algorithm designed for data-parallel computing on modern
      graphics processing units to alleviate the computational burden. We apply
      Gaussian interpolation to create a continuous surface representation from
      discrete input object points. The algorithm maintains a potential occluder list
      for each individual hologram plane sample to keep the number of visibility tests
      to a minimum. We experimented with two approximations that simplify and
      accelerate occlusion computation. It is observed that letting several neighboring
      hologram plane samples share visibility information on object points leads to
      significantly faster computation without causing noticeable artifacts in the
      reconstructed images. Computing a reduced sample set via nonuniform sampling is
      also found to be an effective acceleration technique.

PMID- 20029586
TI  - Homodyne readout on dc-removed coaxial holographic data storage.
AB  - Multiplexing characteristics of a dc-removed coaxial holographic storage system
      were evaluated for what is believed to be the first time. Our dc-removed coaxial
      system achieved 3.5 times higher raw data density than a conventional coaxial
      system that involved dc recording. The increase of the data density was due not
      only to less M/# consumption but also to the effects of signal amplification and
      noise reduction by use of the positive and negative images reconstructed from the
      same holograms.

PMID- 20029587
TI  - Normalization of fringe patterns using the bidimensional empirical mode
      decomposition and the Hilbert transform.
AB  - We evaluate a data-driven technique to perform bias suppression and modulation
      normalization of fringe patterns. The proposed technique uses a bidimensional
      empirical mode decomposition method to decompose a fringe pattern in a set of
      intrinsic frequency modes and the partial Hilbert transform to characterize the
      local amplitude of the modes in order to perform the normalization. The
      performance of the technique is tested using computer simulated fringe patterns
      of different fringe densities and illumination defects with high local variations
      of the modulation, and its advantages and limitations are discussed. Finally, the
      performance of the normalization approach in processing real data is also
      illustrated.

PMID- 20029588
TI  - Real-time three-color reflection holographic interferometer.
AB  - A compact real-time three-color reflection holographic interferometer (RCRHI) was
      developed by Office National d'Etudes et de Recherches Aerospatiales for
      analyzing high-speed flows. As a classical in-line Lippmann-Denisyuk holographic
      setup, a reflection panchromatic silver-halide holographic plate is used to
      simultaneously record three reference holograms. The best results are obtained
      when the diffraction efficiency of the holographic plate reaches 50% for the
      three wavelengths used (red-green-blue). For that, problems in gelatin shrinkage
      due to the hologram treatment had to be solved for the two types of holographic
      plates used (Slavich and Gentet). This new optical setup was applied to analyze
      the two-dimensional unsteady wake flow around a circular cylinder at Mach 0.45.
      Interferograms recorded at a high framing rate exhibit very well saturated colors
      and high contrast, which eases the quasi-automated interferogram analysis.
      Finally, the evolution in time of the instantaneous gas density field has been
      obtained from the analysis of several interferograms covering one period of the
      phenomenon. In the future, the analysis of three-dimensional flows should be
      investigated using an optical bench based on RCRHI multidirectional tomography.

PMID- 20029589
TI  - Model reduction using wavelet multiresolution technique applied to fluorescence
      diffuse optical tomography.
AB  - Fluorescence diffuse optical tomography is a powerful tool for the investigation
      of molecular events in studies for new therapeutic developments. Here, the stress
      is put on the mathematical problem of tomography, which can be formulated in
      terms of an estimation of physical parameters appearing as a set of partial
      differential equations and solved by the finite element method. This method is
      well known to be time consuming, and our principal objective is to reduce the
      model in order to speed up computation. A method based on a wavelet
      multiresolution technique is presented in detail. A validation study was
      conducted on synthetic data and experiments.

PMID- 20029590
TI  - Spatial carrier fringe pattern phase demodulation by use of a two-dimensional
      real wavelet.
AB  - A two-dimensional continuous wavelet transform employing a real mother wavelet is
      applied to phase analysis of spatial carrier fringe patterns. In this method, a
      Hilbert transform is first performed on a carrier fringe pattern to get an
      analytic signal. Then a two-dimensional wavelet transform is calculated for the
      signal that is yielded by the first transform. Finally, the height-demodulated
      phase information can be gotten from the wavelet transform coefficients at the
      wavelet ridge position. The performance of the proposed method has been evaluated
      by using computer-generated and real fringe patterns. The result performed better
      than that of one-dimensional real wavelet transform algorithms in the area with
      phase discontinuous points and high phase variation, especially when there is
      much noise in the fringe patterns. Computer simulations and experiments verified
      the validity of the proposed method.

PMID- 20029591
TI  - Phase shifting digital holography implemented with a twisted-nematic liquid
      crystal display.
AB  - We describe and experimentally demonstrate a phase shifting method based on the
      lateral displacement of a grating implemented with a twisted-nematic liquid
      crystal spatial light modulator. This method allows an accurate implementation of
      the phase shift without requiring moving parts. The technique is implemented in a
      Mach-Zehnder digital holography setup in which the field transmitted by the
      sample object freely propagates to the hologram plane.

PMID- 20029592
TI  - Uncertainties in extracted parameters of a Gaussian emission line profile with
      continuum background.
AB  - We derive analytical equations for uncertainties in parameters extracted by
      nonlinear least-squares fitting of a Gaussian emission function with an unknown
      continuum background component in the presence of additive white Gaussian noise.
      The derivation is based on the inversion of the full curvature matrix (equivalent
      to Fisher information matrix) of the least-squares error, chi(2), in a four
      variable fitting parameter space. The derived uncertainty formulas (equivalent to
      Cramer-Rao error bounds) are found to be in good agreement with the numerically
      computed uncertainties from a large ensemble of simulated measurements. The
      derived formulas can be used for estimating minimum achievable errors for a given
      signal-to-noise ratio and for investigating some aspects of measurement setup
      trade-offs and optimization. While the intended application is Fabry-Perot
      spectroscopy for wind and temperature measurements in the upper atmosphere, the
      derivation is generic and applicable to other spectroscopy problems with a
      Gaussian line shape.

PMID- 20029593
TI  - Photonic NOT and NOR gates based on a single compact photonic crystal ring
      resonator.
AB  - New all-optical NOT and NOR logic gates based on a single ultracompact photonic
      crystal ring resonator (PCRR) have been proposed. The PCRR was formed by removing
      the line defect along the GammaM direction instead of the conventional GammaX
      direction in a square-pattern cylindrical silicon-rod photonic crystal structure.
      The behavior of the proposed logic gates is qualitatively analyzed with the
      theory of beam interference and then numerically investigated by use of the two
      dimensional finite-difference time-domain method. No nonlinear material is
      required with less than a 2.2 microm effective ring radius. The wavelengths of
      the input signal and the probe signal are the same. This new device can
      potentially be used in on-chip photonic logic-integrated circuits.

PMID- 20029594
TI  - Fiber-optic dipping liquid analyzer: theoretical and experimental study of light
      transmission.
AB  - A fiber-optic dipping liquid analyzer (FDLA) is developed for measuring liquid
      properties such as concentration, refractive index, surface tension, and
      viscosity. An important feature of the FDLA is that a liquid drop is introduced
      on the end face of a fiber probe, and the drop can be regarded as a planar-convex
      lens. The light transmitting path and receiving power are affected by the
      refractive index of the liquid drop. We present a theoretical and experimental
      analysis of the light transmission. A mathematical model of receiving power is
      established based on paraxial refraction imaging and fiber reflective intensity
      modulation methods. Sucrose-water solutions were tested with the FDLA. The
      experimental results agree well with the theoretical analysis.

PMID- 20029595
TI  - Enhancement and suppression of terahertz emission by a Fabry-Perot cavity
      structure with a nonlinear optical crystal.
AB  - We have fabricated Fabry-Perot (FP) cavities in the THz region with a ZnTe
      crystal as a cavity layer by a simple stacking method. We observed more than a
      three times enhancement of the THz emission intensity in the FP cavities compared
      with the bare ZnTe crystal at the frequencies of the resonant modes and stopband
      edges. On the other hand, suppression of the THz emission occurs at frequencies
      in the stopband. The enhancement and suppression of the THz emission are caused
      by the modification of the optical density of state in the FP cavities compared
      to the vacuum.

PMID- 20029596
TI  - Replacers of barcodes for small application areas by using grating dots to
      diffractively form bright points.
AB  - Although barcodes can be used to manage data conveniently, they cannot be applied
      to small areas. Therefore, pointcodes are used to overcome the issue in this
      article. A pointcode uses a pointcode pattern to encode data and uses a pointcode
      image to decode data. A pointcode pattern is composed of many grating dots with
      different specified grating pitches and grating orientations. Moreover, there are
      two grating-dot sizes generated. When a laser beam illuminates a pointcode
      pattern with correct illuminating conditions, a pointcode image corresponding to
      the hidden data is diffractively reconstructed. A pointcode image is composed of
      many bright points with different positions. There are two possible bright-point
      sizes generated. A bright point or two bright points at specified positions are
      used to denote a number. Small pointcode patterns are enough to diffractively
      form pointcode images.

PMID- 20029597
TI  - Geometric characteristics of aberrations of plane-symmetric optical systems.
AB  - The geometric characteristics of aberrations of plane-symmetric optical systems
      are studied in detail with a wave-aberration theory. It is dealt with as an
      extension of the Seidel aberrations to realize a consistent aberration theory
      from axially symmetric to plane-symmetric systems. The aberration distribution is
      analyzed with the spot diagram of a ray and an aberration curve. Moreover, the
      root-mean-square value and the centroid of aberration distribution are discussed.
      The numerical results are obtained with the focusing optics of a toroidal mirror
      at grazing incidence.

PMID- 20029598
TI  - Linewidths below 100 kHz with external cavity diode lasers.
AB  - The linewidth of external cavity diode lasers (ECDLs) is an increasingly
      important characteristic for experiments in coherent optical communications and
      atomic physics. The Schawlow-Townes and time-averaged linewidths depend on free
      parameters of the design, such as cavity length, power, and grating
      characteristics. We show that the linewidth is also sensitive to the focus, set
      by the distance between the laser and the collimating lens, due to the effect on
      the external cavity backcoupling efficiency. By considering these factors, a
      simple ECDL can readily achieve linewidths below 100 kHz.

PMID- 20029599
TI  - Performance comparison between Shack-Hartmann and astigmatic hybrid wavefront
      sensors.
AB  - Simulations on Kolmogorov phase screens are employed to compare the relative
      performance of an astigmatic hybrid wavefront sensor (AHS) to that of a Shack
      Hartmann sensor (SHS). The AHS is shown to improve phase reconstruction accuracy
      when the subaperture phase contains significant energy in curvature modes and a
      moderate to high number of photons are collected. Dual use of the AHS and SHS may
      extend enhanced reconstruction to low signal levels. The AHS is also shown to
      have a small benefit for tilt-only reconstruction when the beam has sufficient
      power.

PMID- 20029600
TI  - Matched spectral filter based on reflection holograms for analyte identification.
AB  - A matched spectral filter set that provides automatic preliminary analyte
      identification is proposed and analyzed. Each matched spectral filter in the set
      containing the multiple spectral peaks corresponding to the Raman spectrum of a
      substance is capable of collecting the specified spectrum into the detector
      simultaneously. The filter set is implemented by multiplexed volume holographic
      reflection gratings. The fabrication of a matched spectral filter in an
      Fe:LiNbO(3) crystal is demonstrated to match the Raman spectrum of the sample
      Rhodamine 6G (R6G). An interference alignment method is proposed and used in the
      fabrication to ensure that the multiplexed gratings are in the same direction at
      a high angular accuracy of 0.0025 degrees . Diffused recording beams are used to
      control the bandwidth of the spectral peaks. The reflection spectrum of the
      filter is characterized using a modified Raman spectrometer. The result of the
      filter's reflection spectrum matches that of the sample R6G. A library of such
      matched spectral filters will facilitate a fast detection with a higher
      sensitivity and provide a capability for preliminary molecule identification.

PMID- 20029601
TI  - Stabilization of a self-referenced, prism-based, Cr:forsterite laser frequency
      comb using an intracavity prism.
AB  - The frequency comb from a prism-based Cr:forsterite laser has been frequency
      stabilized using intracavity prism insertion and pump power modulation. Absolute
      frequency measurements of a CW fiber laser stabilized to the P(13) transition of
      acetylene demonstrate a fractional instability of approximately 2 x 10(-11) at a
      1 s gate time, limited by a commercial Global Positioning System (GPS)
      disciplined rubidium oscillator. Additionally, absolute frequency measurements
      made simultaneously using a second frequency comb indicate relative instabilities
      of 3 x 10(-12) for both combs for a 1 s gate time. Estimations of the carrier
      envelope offset frequency linewidth based on relative intensity noise and the
      response dynamics of the carrier-envelope offset to pump power changes confirm
      the observed linewidths.

PMID- 20029602
TI  - Absorption and scattering of 1.06 microm laser radiation from oceanic aerosols.
AB  - The absorption and scattering of oceanic aerosols are characterized using low-
      and high-power lasers in the near IR (1.064 microm). The imaginary part of the
      refractive index of sea salt inferred from low-power absorption measurements is
      200x less than the commonly accepted value from the literature. The measured
      absorption coefficients of natural and artificial saltwater are within 5% of the
      absorption of pure water (0.14 cm(-1)). High-power aerosol experiments are
      consistent with low-power liquid absorption measurements, which yield comparable
      absorption coefficients for pure water and saltwater. High-power illumination of
      test aerosols (CuSO(4).5H(2)O) with an absorption coefficient alpha > or = 0.19
      cm(-1) and a dwell time of 100 ms results in a consistent reduction in scattering
      from the aerosol column. The high-power laser scattering measurements are in good
      agreement with the theory, which accounts for the absorption, heating, and
      vaporization of the water-based aerosols. The measured absorption of oceanic
      aerosols in the laboratory is much less than the literature values at 1.064
      microm and should result in reduced heating and thermal blooming in open ocean
      atmospheres.

PMID- 20029603
TI  - Trajectory and velocity measurement of a particle in spray by digital holography.
AB  - We present a method for the trajectory and the velocity measurement of a particle
      in spray by digital holography. Based on multiple exposure digital in-line
      holography, a sequence of digital holograms of a dynamic spray particle field at
      different times are recorded with a CW laser and a high-speed CCD. The time
      evolution of the serial positions of particles, i.e., the motion trajectories of
      the particles, is obtained by numerically reconstructing the synthetic hologram
      of a sequence of digital holograms. The center coordinate (x,y) of each particle
      image can be extracted using a Hough transform and subpixel precision computing,
      and the velocity of an individual particle can also be obtained, which is then
      applied to measuring the velocity of diesel spray and alcohol spray. The research
      shows that the method presented in this paper for measuring spray field is
      feasible.

PMID- 20029604
TI  - Predispensing of antivirals to high-risk individuals in an influenza pandemic.
AB  - We consider the net benefits of predispensing antivirals to high-risk individuals
      during an influenza pandemic, where the measure of the benefit is the number of
      severe outcomes (such as deaths or hospitalizations) prevented by antivirals in
      the whole population. One potential benefit of predispensing is that individuals
      to whom antivirals have been predispensed may be able to initiate treatment
      earlier than if they had to wait to obtain and fill a prescription, reducing
      their risk of progression to severe disease. If this benefit exceeds the side
      effects of misuse for the category of individuals to whom antivirals were
      predispensed, and if antiviral supply exceeds overall population demand (which
      appears relevant for several countries including US in the current H1N1
      pandemic), predispensing a quantity of antivirals not exceeding the difference
      between supply and demand is always beneficial. In this paper we consider the net
      benefits of predispensing antivirals under various scenarios, including demand
      exceeding supply, and derive mathematical conditions under which antiviral
      predispensing is advantageous on balance. For individuals whose relative risk of
      severe outcome is high enough, such as immunosuppressed individuals (particularly
      children) and possibly individuals with neurological disorders, predispensing is
      always beneficial at a given level of antiviral stockpile with modest assumptions
      on the relative benefit of early treatment by a predispensed course, regardless
      of the overall population demand for antivirals during the course of an epidemic.
      Making additional assumptions on either the overall population demand for
      antivirals (which appear relevant in the current situation) or on the relative
      benefit of predispensing would make predispensing net beneficial with inclusion
      of a larger number of persons such as pregnant women and morbidly obese adults.

PMID- 20029605
TI  - The Contribution of the PB1-F2 protein to the fitness of Influenza A viruses and
      its recent evolution in the 2009 Influenza A (H1N1) pandemic virus.
AB  - The absence of a full-length PB1-F2 protein has been suggested as one possible
      determinant for the low pathogenicity of the 2009 Influenza A H1N1 pandemic
      strain. Since the PB1-F2 sequence of this strain has three stop codons and its
      ancestors encode a full-length protein, the stop codons must have appeared
      recently. This suggests that the PB1-F2 protein is not evolutionary and
      functionally important for the new virus. We investigate the role of this protein
      in the evolution of influenza A viruses, and in particular in relation to the
      history of the new strain. We show that its evolutionary history is comparable to
      other, non-translated, subsequences in the PB1 segment, suggesting that PB1-F2
      does not contribute significantly to the fitness of the influenza A virus.

PMID- 20029606
TI  - Fitness of pandemic H1N1 and seasonal influenza A viruses during co-infection:
      evidence of competitive advantage of pandemic H1N1 influenza versus seasonal
      influenza.
AB  - On June 11, 2009 the World Health Organization (WHO) declared a new H1N1
      influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and
      H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new
      virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2
      human strains. Using the ferret model, we investigated which of these three
      possibilities were most likely favored. Our studies showed that the current
      pandemic virus is more transmissible than, and has a biological advantage over,
      prototypical seasonal H1 or H3 strains.

PMID- 20029607
TI  - Mortality and morbidity burden associated with A/H1N1pdm influenza virus.
AB  - Who is likely to be infected, experience clinical symptoms, or die from the
      H1N1pdm 2009 pandemic virus? Here we use lessons from past influenza pandemics
      and recent information about the H1N1pdm pandemic to discuss variations in
      H1N1pdm disease burden with age, underlying risk factors, and geography.

PMID- 20029608
TI  - Tracking the evolution and geographic spread of Influenza A.
AB  - The 2009 swine-origin strain of Influenza A H1N1 has spread to nearly all parts
      of the world, with 175 countries reporting confirmed cases thus far. Consistent
      with seasonal flu outbreaks, the current pandemic strain has shown rapid
      dispersal, with multiple examples of introduction into different geographic
      regions. Here we use an automated pipeline to collect data for analysis in the
      geospatial package GenGIS, which allows the geographic and temporal tracking of
      new sequence types and polymorphisms. Using this approach, we examine a pair of
      amino acid changes in the neuraminidase protein that are implicated in antibody
      recognition, and exhibit global dispersal with little or no geographic structure.

PMID- 20029609
TI  - Molecular modeling of swine influenza A/H1N1, Spanish H1N1, and avian H5N1 flu N1
      neuraminidases bound to Tamiflu and Relenza.
AB  - A molecular model of the swine influenza A/H1N1 type-I neuraminidase was built
      using the pathogenic avian H5N1 type-I neuraminidase as a basis, due to the
      higher sequence identity between A/H1N1 and H5N1 (91.47%) compared to Spanish
      H1N1 (88.37%) neuraminidase. All-atom molecular dynamics (MD) simulations of all
      three neuraminidases were performed, either as apo-structures or with commercial
      antiviral drugs Tamiflu or Relenza separately bound; the simulations allowed for
      the identification of both conserved and unique drug-protein interactions across
      all three proteins. Specifically, conserved networks of hydrogen bonds
      stabilizing the drugs in the sialic acid binding site of the simulated
      neuraminidases are analyzed, providing insight into how disruption due to
      mutations may lead to increased drug resistance. In addition, a possible
      mechanism through which the residue 294 mutation acquires drug resistance is
      proposed by mapping the mutation site onto an electrostatic pathway which may
      play a role in controlling drug access to the binding pocket of neuraminidase,
      establishing a starting point for further investigations of neuraminidase drug
      resistance.

PMID- 20029611
TI  - Adjuvant is necessary for a robust immune response to a single dose of H1N1
      pandemic flu vaccine in mice.
AB  - Pandemic H1N1 influenza vaccine antigens are currently being manufactured. The
      MF(59) adjuvant has an established safety profile in humans and a proven ability
      to increase responses to some influenza vaccines in humans. To inform initial
      decisions on the use of these vaccine components to protect human populations, we
      have immunized mice with MF(59)-adjuvanted or non-adjuvanted pandemic influenza
      vaccine. Immunizing unprimed mice with a single dose of MF(59)-adjuvanted vaccine
      elicits functional antibody titers equivalent to those associated with protection
      of humans from seasonal influenza. Without adjuvant, two doses are required for a
      robust antibody response. Unadjuvanted vaccines with 0.5 and 1 microgram of
      antigen elicit equivalent titers. These data support including MF(59) in pandemic
      flu vaccines to rapidly protect young adults and children, who may have little or
      no previous exposure to influenza infection or immunization.

PMID- 20029610
TI  - Reassortment patterns in Swine influenza viruses.
AB  - Previous human influenza pandemics were the results of emerging viruses from non
      human reservoirs, with at least two caused by strains of mixed human and avian
      origin. Also, many cases of swine influenza viruses have reportedly infected
      humans, including the recent human H1N1 strain, isolated in Mexico and the United
      States. Pigs are documented to get infected with human, avian, and swine viruses
      and allow productive replication, thus it has been conjectured that they are the
      "mixing vessel" that create reassortant strains, causing the human pandemics. In
      this paper, we apply several statistical techniques to an ensemble of publicly
      available swine viruses to study the reassortment phenomena. The reassortment
      patterns in swine viruses confirm previous results found in human viruses that
      the glycoprotein coding segments reassort most often. Moreover, one of the
      polymerase segments (PB1), reassorted in the strains responsible for the last two
      human pandemics of 1957 and 1968, also reassorts frequently.

PMID- 20029612
TI  - Top-hits for H1N1pdm identified by virtual screening using ensemble-based
      docking: top-hits for A/H1N1 identified by virtual screening using ensemble-based
      docking.
AB  - A list of 27 promising antiviral drugs are proposed for use against the H1N1pdm
      strain. Since the binding site of the H1N1pdm neuraminidase is similar to that of
      the bird flu H(5)N1, an effective means to quickly identify top candidates for
      use against H1N1pdm is to use known bird-flu drugs and the 27 compounds from the
      NCI diversity set which bind best to H(5)N1 neuraminidase. These compounds serve
      as viable candidates for docking against the H1N1pdm neuraminidase, using
      ensembles extracted from molecular dynamics simulations of the H1N1pdm system.
      The ranking order of these top candidates was found to be different from the
      previously published results for H(5)N1. The results indicated that the
      Oseltamivir (Tamiflu) and Peramivir drugs have higher ranking than Zanamivir
      (Relenza). However, six drug candidates were found to bind more effectively to
      H1N1pdm neuraminidase than Tamiflu. Detailed hydrogen bond network analysis for
      these six candidates is also provided.

PMID- 20029613
TI  - Reconstructing the initial global spread of a human influenza pandemic: a
      Bayesian spatial-temporal model for the global spread of H1N1pdm.
AB  - Here, we present an analysis of the H1N1pdm genetic data sampled over the initial
      stages in the epidemic. To infer phylodynamic spread in time and space we employ
      a recently developed Bayesian statistical inference framework (Lemey et al., in
      press). We model spatial diffusion as a continuous-time Markov chain process
      along time-measured genealogies. In this analysis, we consider 40 locations for
      which sequence data were available on 06-Aug-2009. The sampling time interval of
      the 242 sequences spans from 30-Mar-2009 to 12-Jul-2009. The Bayesian inference
      typically results in a posterior distribution of phylogenetic trees, each having
      an estimate of the epidemic locations at the ancestral nodes in the tree. We
      summarize these trees using the most representative clustering pattern and
      annotate these clusters with the most probable location states. We can visualize
      this information as tree that grows over time, seeding locations each time an
      ancestral node is inferred to exist at a different location. A Bayes factor test
      provides statistical support for epidemiological linkage throughout the
      evolutionary history. We demonstrate how our full probabilistic approach
      efficiently tracks an epidemic based on viral genetic data as it unfolds across
      the globe.

PMID- 20029615
TI  - E14-F55 combination in M2 protein: a putative molecular determinant responsible
      for swine-origin influenza A virus transmission in humans.
AB  - The species-specific signatures of the swine-origin influenza A (H1N1) virus (S
      OIV), which caused the current influenza pandemic, have not been well defined. By
      comparing the protein sequences of S-OIVs with those of swine, avian and human
      influenza viruses, we found that that almost all human IAVs and those causing
      influenza pandemics, including the 2009 S-OIVs, had a combination of glutamic
      acid (E) residue at position 14 and phenylalanine (F) residue at position 55 in
      their M2 protein, while only 22% and 4% of the swine and avian IAVs had the E14
      F55 combination. These finding suggests that E14-F55 combination in the M2
      protein of S-OIV may be a molecular determinant associated with its human-to
      human transmission.

PMID- 20029614
TI  - The severity of pandemic H1N1 influenza in the United States, April -- July 2009.
AB  - BACKGROUND: Accurate measures of the severity of pandemic influenza A/H1N1
      (pH1N1) are needed to assess the likely impact of an anticipated resurgence in
      the autumn in the Northern Hemisphere. Severity has been difficult to measure
      because jurisdictions with large numbers of deaths and other severe outcomes have
      had too many cases to assess the total number with confidence. Also, detection of
      severe cases may be more likely. METHODS AND FINDINGS: We used complementary data
      from two US cities: Milwaukee attempted to identify cases of medically attended
      infection whether or not they required hospitalization, while New York City
      focused on the identification of hospitalizations, intensive care admission or
      mechanical ventilation (hereafter, ICU), and deaths. New York data were used to
      estimate numerators for ICU and death, and two sources of data: medically
      attended cases in Milwaukee or self-reported influenza-like illness in New York,
      were used to estimate ratios of symptomatic cases:hospitalizations. Combining
      these data with estimates of the fraction detected for each level of severity, we
      estimated the proportion of symptomatic cases that died (symptomatic case
      fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR),
      overall and by age category. Evidence, prior information and associated
      uncertainty were analyzed in a Bayesian evidence synthesis framework. Using
      medically attended cases and estimates of the proportion of symptomatic cases
      medically attended, we estimated sCFR of 0.045% (95% credible interval, CI 0.020%
      0.090%), sCIR of 0.222% (0.105%-0.425%), and sCHR of 1.37% (0.68%-2.52%). Using
      self-reported ILI, we obtained estimates approximately 6-9 times lower. sCFR was
      highest in the 18-64 age group, and sCIR and sCHR highest in the 18-64 or 0-4 age
      group depending on the approach. CONCLUSIONS: These estimates suggest that an
      autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead
      to a number of deaths in the range from considerably below that associated with
      seasonal influenza to slightly higher, but with greatest impact in young children
      and non-elderly adults. These estimates of impact depend on assumptions about
      total incidence of infection and would be larger if incidence of symptomatic
      infection were higher or shifted toward adults, if viral virulence increased, or
      if suboptimal treatment resulted from stress on the health care system; numbers
      would decrease if the proportion infected or symptomatic were lower.

PMID- 20029617
TI  - Hypotheses on mechanisms linking cardiovascular and psychiatric/neurological
      disorders.

PMID- 20029616
TI  - The shifting demographic landscape of influenza.
AB  - BACKGROUND: As Pandemic (H1N1) 2009 influenza spreads around the globe, it
      strikes school-age children more often than adults. Although there is some
      evidence of pre-existing immunity among older adults, this alone may not explain
      the significant gap in age-specific infection rates. METHODS AND FINDINGS: Based
      on a retrospective analysis of pandemic strains of influenza from the last
      century, we show that school-age children typically experience the highest attack
      rates in primarily naive populations, with the burden shifting to adults during
      the subsequent season. Using a parsimonious network-based mathematical model
      which incorporates the changing distribution of contacts in the susceptible
      population, we demonstrate that new pandemic strains of influenza are expected to
      shift the epidemiological landscape in exactly this way. CONCLUSIONS: Our results
      provide a simple demographic explanation for the age bias observed for H1N1/09
      attack rates, and a prediction that this bias will shift in coming months. These
      results also have significant implications for the allocation of public health
      resources including vaccine distribution policies.

PMID- 20029618
TI  - The potential for xanthine oxidase inhibition in the prevention and treatment of
      cardiovascular and cerebrovascular disease.
AB  - There is a now a wealth of epidemiological, animal, and clinical data to suggest
      the benefits of uric acid reduction and hxanthine oxidase inhibition in
      prevention of vascular disease. This review discusses the available
      epidemiological, preclinical, and clinical data and considers arguments for and
      against a role for serum uric acid in common cardiovascular disorders. It
      concludes that large scale trials with clinical endpoints are justified to
      address this important question and to define whether use of drugs such as
      allopurinol should be a routine part of preventative strategies.

PMID- 20029619
TI  - Do Neural Cells Communicate with Endothelial Cells via Secretory Exosomes and
      Microvesicles?
AB  - Neurons, glial, cells, and brain tumor cells tissues release small vesicles
      (secretory exosomes and microvesicles), which may represent a novel mechanism by
      which neuronal activity could influence angiogenesis within the embryonic and
      mature brain. If CNS-derived vesicles can enter the bloodstream as well, they may
      communicate with endothelial cells in the peripheral circulation and with cells
      concerned with immune surveillance.

PMID- 20029620
TI  - Chromatin from peripheral blood mononuclear cells as biomarkers for epigenetic
      abnormalities in schizophrenia.
AB  - Background. Studies have implicated abnormalities in epigenetic gene regulation
      in schizophrenia. Presentation. We hypothesize that identifying abnormalities in
      chromatin structure and the epigenetic machinery in peripheral blood mononuclear
      cells (PBMC) from schizophrenia patients could (a) help characterize a subset of
      schizophrenia patients and (b) lead to targeted pharmacological interventions.
      Testing. Investigate the relationship between clinical symptoms, demographics,
      hormonal fluctuations, substance abuse, disease characteristics across the major
      mental illnesses, and epigenetic parameters in PBMC. In addition, examine the
      effects of individual antipsychotics, mood stabilizers, as well as experimental
      agents both as clinically prescribed as well as in cultured PBMC to understand
      the effects of these agents on chromatin. Implications. If PBMC could serve as a
      reliable model of overall epigenetic mechanisms then this could lead to a
      "biomarker" approach to revealing pathological chromatin state in schizophrenia.
      This approach may provide an informed method for selecting chromatin modifying
      agents for psychiatric disorders.

PMID- 20029621
TI  - Possible Role of Platelet GluR1 Receptors in Comorbid Depression and
      Cardiovascular Disease.
AB  - The exact nature of the comorbidity between cardiovascular disease (CVD) and
      major depressive disorder (MDD) is poorly understood. The proposed mechanisms
      include various biochemical and molecular pathways as well as health behaviors
      such as physical inactivity. One possible link between MDD and CVD is increased
      platelet activity and blood viscosity. Recently, it was discovered that platelets
      express functional subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acid (AMPA) receptors, for example, glutamate receptor 1 (GluR1). Here, I propose
      that this type of AMPA receptor could play a role in comorbid MDD and CVD, and
      antidepressants may interfere with platelet activation via direct or indirect
      effects on platelet GluR1 phosphorylation. Testing this hypothesis could provide
      a novel view on the pathobiological mechanisms of comorbid MDD and CVD. With
      respect to the recently discovered role of AMPA receptors in regulating platelet
      activation and thrombosis, it appears that the information about the putative
      effects of psychoactive AMPA-modifying drugs on platelet AMPA receptors would be
      critical in evaluating the putative effects of such drugs on CVD.

PMID- 20029622
TI  - Heart and brain tissue banks for research on co-occurring cardiovascular and
      neurological/psychiatric disorders.
AB  - Epidemiological studies point to a strong and possibly causal association of
      psychiatric and neurological disorders with cardiovascular disease (CVD).
      Mechanistic links between these co-occurring illnesses are not well understood.
      Better insight into their relationship could help identify novel diagnostic
      markers and therapeutic targets. For successful translation of basic biomedical
      research into clinical practice, analyses of postmortem human tissues are
      essential. However, current tissue banks dedicated to psychiatric and
      neurological research collect only brain tissue samples deemed most important to
      the institution's participating investigators. While this practice is often
      dictated by budget constraints, restricted tissue storage space and other
      practical reasons, it limits the ability of the biological research community to
      access and study multiple organ systems relevant to cardiovascular and neuronal
      systems dysfunction. This problem is worsened when clinical records pertaining to
      coexistent systemic pathology are not available. To promote further understanding
      of co-occurring CVD and psychiatric/neurological disorders, efforts should be
      made to support tissue banks that harvest heart, coronary arteries, and aorta
      samples as well as brain tissue, from the same subjects.

PMID- 20029623
TI  - Depression with panic episodes and coronary vasospasm.
AB  - Variant (Prinzmetal's) angina is an uncommon cause of precordial pain caused by
      coronary vasospasm and characterized by transient ST elevation and negative
      markers of myocardial necrosis. This is the case of a female patient with a prior
      history of depression and panic attacks who presented with recurrent symptoms
      including chest pain. A cardiac event monitor positively documented coronary
      vasospasm associated with anxiety-provoking chest pain, whereas the coronary
      arteries were angiographically normal. We noted that the frequency of angina
      attacks apparently increased during the period that coincided with the
      introduction of Bupropion SR for treatment of the patient's depression.
      Considering the possibility of bupropion-associated negative impact on coronary
      vasospasm, the antidepressant therapy was adjusted to exclude this drug. Although
      Prinzmetal's angina is relatively uncommon, we suspect that a routine use of
      cardiac event monitors in subjects with panic disorder might reveal a greater
      incidence of coronary vasospasm in this patient population.

PMID- 20029624
TI  - Serotonin 5-HT(2A) Receptor Function as a Contributing Factor to Both
      Neuropsychiatric and Cardiovascular Diseases.
AB  - There are high levels of comorbidity between neuropsychiatric and cardiovascular
      disorders. A key molecule central to both cognitive and cardiovascular function
      is the molecule serotonin. In the brain, serotonin modulates neuronal activity
      and is actively involved in mediating many cognitive functions and behaviors. In
      the periphery, serotonin is involved in vasoconstriction, inflammation, and cell
      growth, among other processes. It is hypothesized that one component of the
      serotonin system, the 5-HT(2A) receptor, is a common and contributing factor
      underlying aspects of the comorbidity between neuropsychiatric and cardiovascular
      disorders. Within the brain this receptor participates in processes such as
      cognition and working memory, been implicated in effective disorders such as
      schizophrenia, and mediate the primary effects of hallucinogenic drugs. In the
      periphery, 5-HT(2A) receptors have been linked to vasoconstriction and
      hypertension, and to inflammatory processes that can lead to atherosclerosis.

PMID- 20029625
TI  - P2X(7) Receptors as a Transducer in the Co-Occurrence of Neurological/Psychiatric
      and Cardiovascular Disorders: A Hypothesis.
AB  - Background. Over-stimulation of the purinergic P2X(7) receptor may bring about
      cellular dysfunction and injury in settings of neurodegeneration, chronic
      inflammation, as well as in psychiatric and cardiovascular diseases. Here we
      speculate how P2X(7) receptor over-activation may lead to the co-occurrence of
      neurological and psychiatric disorders with cardiovascular disorders.
      Presentation. We hypothesize that proinflammatory cytokines, in particular
      interleukin-1beta, are key players in the pathophysiology of neurological,
      psychiatric, and cardiovascular diseases. Critically, this premise is based on a
      role for the P2X(7) receptor in triggering a rise in these cytokines. Given the
      broad distribution of P2X(7) receptors in nervous, immune, and vascular tissue
      cells, this receptor is proposed as central in linking the nervous, immune, and
      cardiovascular systems. Testing. Investigate, retrospectively, whether a
      bidirectional link can be established between illnesses with a proinflammatory
      component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular
      disease, for example, hypertension, and whether patients treated with anti
      inflammatory drugs have a lower incidence of disease complications. Positive
      outcome would indicate a prospective study to evaluate therapeutic efficacy of
      P2X(7) receptor antagonists. Implications. It should be stressed that sufficient
      direct evidence does not exist at present supporting our hypothesis. However, a
      positive outcome would encourage the further development of P2X(7) receptor
      antagonists and their application to limit the co-occurrence of neurological,
      psychiatric, and cardiovascular disorders.

PMID- 20029626
TI  - Cardiovascular disease and psychiatric comorbidity: the potential role of
      perseverative cognition.
AB  - The high comorbidity between psychiatric disorders and cardiovascular disease has
      received increasing attention, yet little is known about the processes linking
      the two. One plausible contributing mechanism is the tendency of those with
      psychiatric disorders to ruminate on stressful events. This phenomenon, sometimes
      called perseverative cognition, can extend the psychological and physiological
      effects of stress, which could contribute to cardiovascular disease etiology. In
      this paper, we discuss the potential role of perseverative cognition in mediating
      the relationship between psychiatric illness and cardiovascular disease.
      Rumination can delay physiological recovery from acute stress, which in turn has
      been found to predict future cardiovascular health. This delayed recovery could
      act as a mechanism in the longitudinal link between worry and cardiovascular
      health. The cognitive inflexibility that characterizes mood and anxiety disorders
      may then contribute to disease not by producing greater reactivity, but instead
      through extending activation, increasing the risks for cardiovascular damage.

PMID- 20029627
TI  - Putative Role of MicroRNA-Regulated Pathways in Comorbid Neurological and
      Cardiovascular Disorders.
AB  - Background. The conserved noncoding microRNAs (miRNAs) that function to regulate
      gene expression are essential for the development and function of the brain and
      heart. Changes in miRNA expression profiles are associated with an increased risk
      for developing neurodegenerative disorders as well as heart failure. Here, the
      hypothesis of how miRNA-regulated pathways could contribute to comorbid
      neurological and cardiovascular disorders will be discussed. Presentation.
      Changes in miRNA expression occurring in the brain and heart could have an impact
      on coexisting neurological and cardiovascular characteristics by (1) modulating
      organ function, (2) accentuating cellular stress, and (3) impinging on neuronal
      and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in
      the brain and heart tissues from individuals with comorbid neurodegenerative and
      cardiovascular disorders will be of great importance and relevance. Implications.
      Careful experimental design will shed light to the deeper understanding of the
      molecular mechanisms tying up those different but yet somehow connected diseases.

PMID- 20029628
TI  - Omega-3 Polyunsaturated Fatty Acids (n-3 PUFAs) in Cardiovascular Diseases (CVDs)
      and Depression: The Missing Link?
AB  - Background. Based on epidemiological data, clinical trials, and meta-analytic
      reviews, omega-3 polyunsaturated fatty acids (n-3 PUFAs) seem to be a biological
      link between depression and cardiovascular diseases (CVDs). Presentation.
      Involvement of n-3 PUFAs in depression and CVDs may be associated with a chronic,
      low-grade, inflammation. We hypothesize that n-3 PUFAs link depression and CVDs
      via "PUFA-prostaglandin E2 (PGE2) cascade." Testing. To further support our
      hypothesis, case-control studies are needed to test the role of COX2 and PLA2
      functions in depression and in CVDs. In addition, the effects of n-3 PUFAs on
      cardiovascular markers in depression and on depressive symptoms in CVDs should be
      investigated in clinical trials. Finally, the effects of manipulating COX2 and
      PLA2 functions on depression-like behaviors and cardiovascular functions could be
      explored in animal studies. Implications. n-3 PUFAs might be a promising
      treatment for both cardiovascular diseases and depression via its anti
      inflammatory, cardioprotective, and neuroprotective effects.

PMID- 20029629
TI  - Retrusive chin reconstruction after burn injuries using submental and labiomental
      fat flaps: an innovative method.
AB  - OBJECTIVE: A simple method has been introduced for augmentation and restoration
      of normal chin protrusion as an important element of facial contour in patients
      suffering from severe skin retraction and scar resulting from head and neck area
      burns. PATIENTS AND METHODS: For releasing skin retraction and compression of the
      mental area subcutaneous fat tissues, under general anesthesia, 2 incisions were
      made in the submental and labiomental areas, each about 3 to 5 cm. After
      dissection of the superior portions of labiomental and inferior pedicle of
      submental fat pads, turning over and attaching them together, the skin over the
      area was reconstructed as needed. RESULTS: Thirty-four patients with
      pseudomicrogenia were involved. In 32 patients, the procedure was performed
      successfully and the results were evaluated as excellent in 15 cases and good in
      17 cases. However, in 2 patients, suboptimal results were obtained, which were
      corrected using genioplasty in one of them. The other one did not consent for any
      further surgeries. Split-thickness skin grafting was performed in 3 cases. Tissue
      expansion and full-thickness skin grafting were used in 3 others for resurfacing
      the area. CONCLUSION: Taken together, the current technique might be helpful in
      restoring normal chin protrusion and can be used besides available methods for
      resurfacing and reconstruction of the defective skin for enhancing the facial
      appearance.

PMID- 20029630
TI  - Arginase in parasitic infections: macrophage activation, immunosuppression, and
      intracellular signals.
AB  - A type 1 cytokine-dependent proinflammatory response inducing classically
      activated macrophages (CaMvarphis) is crucial for parasite control during
      protozoan infections but can also contribute to the development of
      immunopathological disease symptoms. Type 2 cytokines such as IL-4 and IL-13
      antagonize CaMvarphis inducing alternatively activated macrophages (AaMvarphis)
      that upregulate arginase-1 expression. During several infections, induction of
      arginase-1-macrophages was showed to have a detrimental role by limiting
      CaMvarphi-dependent parasite clearance and promoting parasite proliferation.
      Additionally, the role of arginase-1 in T cell suppression has been explored
      recently. Arginase-1 can also be induced by IL-10 and transforming growth factor
      beta (TGF-beta) or even directly by parasites or parasite components. Therefore,
      generation of alternative activation states of macrophages could limit collateral
      tissue damage because of excessive type 1 inflammation. However, they affect
      disease outcome by promoting parasite survival and proliferation. Thus,
      modulation of macrophage activation may be instrumental in allowing parasite
      persistence and long-term host survival.

PMID- 20029631
TI  - Detection of GAD65 autoreactive T-cells by HLA class I tetramers in type 1
      diabetic patients.
AB  - Type 1 diabetes (T1D) is an autoimmune disease, in which pancreatic beta cells
      are destroyed in genetically predisposed individuals. While the direct
      contribution of autoantibodies to the disease pathogenesis is controversial, it
      is generally recognised that the mechanism of beta cell destruction is mediated
      by autoreactive T cells that had escaped the thymic selection. We aimed to design
      a method to detect circulating CD8+ T cells autoreactive against an epitope of
      the glutamic acid decarboxylase autoantigen, isoform 65 (GAD65) ex vivo in T1D
      patients by using HLA class I tetramers. Low frequencies of GAD65 peptide
      specific CD8+ cytotoxic T lymphocytes were detected in peripheral blood
      lymphocytes (PBMC) of normal controls after GAD65 peptide-specific stimulation.
      Conversely, their frequencies were significantly higher than in controls in PBMC
      of T1D patients after GAD65 peptide stimulation. These preliminary data are
      encouraging in order to develop a reliable assay to be employed in large-scale
      screening studies.

PMID- 20029632
TI  - Challenges for biomarker discovery in body fluids using SELDI-TOF-MS.
AB  - Protein profiling using SELDI-TOF-MS has gained over the past few years an
      increasing interest in the field of biomarker discovery. The technology presents
      great potential if some parameters, such as sample handling, SELDI settings, and
      data analysis, are strictly controlled. Practical considerations to set up a
      robust and sensitive strategy for biomarker discovery are presented. This paper
      also reviews biological fluids generally available including a description of
      their peculiar properties and the preanalytical challenges inherent to sample
      collection and storage. Finally, some new insights for biomarker identification
      and validation challenges are provided.

PMID- 20029634
TI  - P2X(7) Receptors in Neurological and Cardiovascular Disorders.
AB  - P2X receptors are ATP-gated cation channels that mediate fast excitatory
      transmission in diverse regions of the brain and spinal cord. Several P2X
      receptor subtypes, including P2X(7), have the unusual property of changing their
      ion selectivity during prolonged exposure to ATP, which results in a channel pore
      permeable to molecules as large as 900 daltons. The P2X(7) receptor was
      originally described in cells of hematopoietic origin, and mediates the influx of
      Ca(2+) and Na(+) and Ca(2+) and Na(+) ions as well as the release of
      proinflammatory cytokines. P2X(7) receptors may affect neuronal cell death
      through their ability to regulate the processing and release of interleukin
      1beta, a key mediator in neurodegeneration, chronic inflammation, and chronic
      pain. Activation of P2X(7), a key mediator in neurodegeneration, chronic
      inflammation, and chronic pain. Activation of P2X(7) receptors provides an
      inflammatory stimulus, and P2X(7) receptor-deficient mice have substantially
      attenuated inflammatory responses, including models of neuropathic and chronic
      inflammatory pain. Moreover, P2X(7) receptor activity, by regulating the release
      of proinflammatory cytokines, may be involved in the pathophysiology of
      depression. Apoptotic cell death occurs in a number of vascular diseases,
      including atherosclerosis, restenosis, and hypertension, and may be linked to the
      release of ATP from endothelial cells, P2X(7) receptor activation,
      proinflammatory cytokine production, and endothelial cell apoptosis. In this
      context, the P2X(7) receptor may be viewed as a gateway of communication between
      the nervous, immune, and cardiovascular systems.

PMID- 20029633
TI  - Role of ryanodine receptor subtypes in initiation and formation of calcium sparks
      in arterial smooth muscle: comparison with striated muscle.
AB  - Calcium sparks represent local, rapid, and transient calcium release events from
      a cluster of ryanodine receptors (RyRs) in the sarcoplasmic reticulum. In
      arterial smooth muscle cells (SMCs), calcium sparks activate calcium-dependent
      potassium channels causing decrease in the global intracellular [Ca2+] and oppose
      vasoconstriction. This is in contrast to cardiac and skeletal muscle, where
      spatial and temporal summation of calcium sparks leads to global increases in
      intracellular [Ca2+] and myocyte contraction. We summarize the present data on
      local RyR calcium signaling in arterial SMCs in comparison to striated muscle and
      muscle-specific differences in coupling between L-type calcium channels and RyRs.
      Accordingly, arterial SMC Ca(v)1.2 L-type channels regulate intracellular calcium
      stores content, which in turn modulates calcium efflux though RyRs.
      Downregulation of RyR2 up to a certain degree is compensated by increased SR
      calcium content to normalize calcium sparks. This indirect coupling between
      Ca(v)1.2 and RyR in arterial SMCs is opposite to striated muscle, where
      triggering of calcium sparks is controlled by rapid and direct cross-talk between
      Ca(v)1.1/Ca(v)1.2 L-type channels and RyRs. We discuss the role of RyR isoforms
      in initiation and formation of calcium sparks in SMCs and their possible
      molecular binding partners and regulators, which differ compared to striated
      muscle.

PMID- 20029635
TI  - The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to
      B6C3Fe Mice for Three Generations Elicits Obesity.
AB  - Feeding mice, over 3 generations, an equicaloric diet in which alpha-linolenic
      acid, the dietary precursor of n-3 polyunsaturated fatty acids, was substituted
      by linoleic acid, the dietary precursor of n-6 polyunsaturated fatty acids,
      significantly increased body weight throughout life when compared with standard
      diet-fed mice. Adipogenesis observed in the low n-3 fatty acid mice was
      accompanied by a 6-fold upregulation of stearyl-coenzyme A desaturase 1 (Scd1),
      whose activity is correlated to plasma triglyceride levels. In total liver lipid
      and phospholipid extracts, the sum of n-3 fatty acids and the individual longer
      carbon chain acids, eicosapentaenoic acid (20:5n3), docosapentaenoic acid
      (22:5n3), and docosahexaenoic acid (22:6n3) were significantly decreased whereas
      arachidonic acid (20:4n6) was significantly increased. In addition, low n-3 fatty
      acid-fed mice had liver steatosis, heart, and kidney hypertrophy. Hence, reducing
      dietary alpha-linolenic acid, from 1.02 energy % to 0.16 energy % combined with
      raising linoleic acid intake resulted in obesity and had detrimental consequences
      on organ function.

PMID- 20029636
TI  - Possible treatment concepts for the levodopa-related hyperhomocysteinemia.
AB  - The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD)
      resulted from outcomes of animal-and cell culture studies and the clinical
      observation of motor complication related to the short half life of LD. Further
      aspects of LD long term application, the LD associated homocysteine increase and
      its emerging consequences on progression, and onset of neuropsychiatric symptoms
      and of vascular disease are only partially considered. Therapeutic approaches for
      this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or
      LD application with an inhibitor of catechol-O-methyltransferase (COMT). However,
      forcing central dopamine metabolism further down the methylation path by central
      blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels.
      But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N
      methylated tetrahydroisoquinolines. These compounds were observed in
      cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD
      application with peripheral COMT inhibition may be safer.

PMID- 20029637
TI  - Fast track liver resection: the effect of a comprehensive care package and
      analgesia with single dose intrathecal morphine with gabapentin or continuous
      epidural analgesia.
AB  - BACKGROUND: A comprehensive care package for patients undergoing hepatectomy was
      developed with the aim of minimal physiological disturbance in the peri-operative
      period. Peri-operative analgesia with few gastrointestinal effects and reduced
      requirement for intravenous (IV) fluid therapy was central to this plan. METHODS:
      Data on 100 consecutive patients managed with continuous epidural infusion (n =
      50; bupivicaine 0.125% and fentanyl 2 microg/mL at 0.1 mL/kg/hr) or intrathecal
      morphine (n = 50; 300 microg in combination with oral gabapentin 1200 mg
      preoperatively and 400 mg bd postoperatively) was compared. RESULTS: The epidural
      and intrathecal morphine groups were equivalent in terms of patient demographics,
      procedures and complications. Patients receiving intrathecal morphine received
      less intra-operative IV fluids (median 1500 mL versus 2200 mL, P = .06), less
      postoperative IV fluids (median 1200 mL versus 4300 mL, P = .03) than patients
      receiving epidural infusion. Patients managed with intrathecal morphine
      established a normal dietary intake sooner (16 hours versus 20 hours, P = .05)
      and had shorter hospital stays than those managed with epidural infusions (4.7 +/
      0.9 days versus 6.8 +/- 1.2 days, P = .02). CONCLUSIONS: Single dose intrathecal
      morphine is a safe and effective means of providing peri-operative analgesia.
      Patients managed with intrathecal morphine have reduced peri-operative
      physiological disturbance and return home within a few days of hepatic resection.

PMID- 20029638
TI  - Behavioral intervention versus pharmacotherapy or their combinations in the
      management of overactive bladder dysfunction.
AB  - Overactive bladder syndrome (OAB) refers to individuals with the following
      symptoms: urinary urgency, increased urinary frequency, and urge incontinence.
      These symptoms are not life threatening but can cause embarrassment and
      significantly impact quality of life. There are numerous treatment options for
      OAB, including behavioral therapy, traditional pharmacological therapy or a
      combination of the two. These options are considered the mainstay of treatment
      for OAB. We carried out a comprehensive systematic review of the available
      literature on the effectiveness of behavioral intervention, anticholinergic
      drugs, and their combination in the management of adults with overactive bladder,
      with emphasis on results from clinical trials and primary literature. Each
      treatment intervention is efficacious, and the choice should be based on the
      patient's severity of symptoms, tolerability, compliance and satisfaction with
      the treatment. Based on available literature, management of OAB using a
      combination of behavioral therapy and drug intervention is the most efficacious
      in terms of patient satisfaction, perceived improvement, and reduction of bladder
      symptoms. It is also the most practical and cost effective for optimal management
      of patients with OAB. Pharmacological treatment, in addition to behavioral
      therapy, remains important in the management of adults with OAB syndrome.

PMID- 20029639
TI  - Differences in protein expression and gene amplification of cyclins between colon
      and rectal adenocarcinomas.
AB  - Adenocarcinomas of rectum and colon may be different with regard to the cellular
      biological basis for cancer development. A material of 246 rectal cancers removed
      surgically at Akershus University Hospital in the years 1992-2000 was
      investigated and was compared to a material of 219 colon cancers operated on at
      Akershus University Hospital during the years 1988, 1990 and 1997-2000. There
      were highly significant differences between the rectal and the colon cancers in
      the protein expression of cyclin D1, cyclin D3, cyclin E, nuclear beta-catenin,
      and c-Myc and in gene amplification of cyclin A2, cyclin B1, cyclin D1, and
      cyclin E. Gene amplification and protein expression in the rectal cancers
      correlated significantly for the cyclins B1, D3, and E. A statistically
      significant relation was observed between overexpression of cyclin A2 and local
      relapse of rectal carcinomas, as higher expression of cyclin A2 was associated
      with lower local recurrence rate.

PMID- 20029640
TI  - Factitious disorders and cardiothoracic surgery: the ongoing multidisciplinary
      challenges of a complex case.
AB  - Chronic factitious disorder, Munchausen's syndrome, can be challenging to manage
      particularly when complaints and symptoms suggest medical or surgical
      emergencies. We present a patient whose problems have spanned many years and a
      great distance. Hopefully, with a greater awareness of this disease, as this
      patient continues to seek health care in many different hospitals, the
      implications of timely access to information, good histories and physical exams,
      and an index of suspicion can assist in potentially avoiding unnecessary,
      expensive, and invasive evaluations.

PMID- 20029641
TI  - Surgical approach to a large left adrenocortical mass with associated tumour
      thrombosis of the left renal vein: preservation of the ipsilateral kidney.
AB  - A sixty-years-old male with diagnosis of a left adrenal mass (146 x 99 x 126 mm)
      with associated tumour thrombosis of the left renal vein with no clear signs of
      thrombosis of the inferior vena cava was admitted for elective surgery Finally an
      adrenalectomy and excision of tumour thrombus preserving the ipsilateral kidney
      was made. Despite of the complex vascular management, this kind of approaches
      allow to preserve normal renal function in patients with future nephrotoxic
      treatment like cisplatin.

PMID- 20029642
TI  - Comparison of two common outpatient preparations for colonoscopy in children and
      youth.
AB  - Colonoscopies are often performed in children for diagnostic and therapeutic
      purposes. Our study compared two bowel-cleansing solutions: sodium picosulphate,
      magnesium oxide, and citric acid (Pico-Salax) with liquid magnesium citrate as
      preparations for colonoscopy. A retrospective chart review of all patients seen
      in the Gastroenterology outpatient clinic and who underwent bowel cleansing in
      preparation for colonoscopy from February to December 2006 was undertaken. Thirty
      two children received Pico-Salax and 36 received liquid magnesium citrate. The
      tolerability of both solutions was similar. Most children in both groups had
      liquid stools and complete colonoscopies. Bowel preparation for a colonoscopy can
      be successfully achieved using either Pico-Salax or liquid magnesium citrate.

PMID- 20029643
TI  - Pole to pole intraocular transit of tarantula hairs-an intriguing cause of red
      eye.
AB  - This intriguing case report provides novel images and a description of the
      anterior and rarer posterior segment findings seen in ocular inflammation
      associated with tarantula spider hair exposure. We present an interventional case
      report of a 9-year-old boy who presented with a red, sore eye. Slit lamp
      examination revealed right eye injection, multiple small hairs at differing
      levels of the cornea with associated opacities and inflammation within the
      anterior and posterior segments of the eye. Only after detailed and repeated
      questioning did the aetiology become apparent. Conservative management in the
      form of topical steroid and antibiotics was commenced and he did well with no
      obvious sequelae in the medium term. Healthcare personnel (and indeed pet shop
      owners, arachnid enthusiasts and even parents) should be aware of the potential
      ocular complications of tarantula hair exposure and clinicians should perhaps
      specifically ask about pet-keeping when presented with an unusual red eye.

PMID- 20029644
TI  - Gastric hyperplastic polyp associated with proliferation of xanthoma cells
      observed by magnification narrow-band imaging endoscopy.
AB  - A case of gastric hyperplastic polyp with proliferation of xanthoma cells is
      reported. The patient was a 69-year-old man who visited our hospital for further
      evaluation of gastric polyps. Endoscopic examination of the upper digestive tract
      revealed multiple hyperplastic polyps in the gastric antrum. There was a
      pedunculated polyp with whitish yellow granules, 7 mm in diameter, arising from
      the greater curvature of the antrum. Magnification narrow-band imaging endoscopy
      (GIF-H260Z, Olympus) revealed long microcapillaries in the polyp but did not
      reveal disappearance of the mucosal microstructure or irregular branched
      capillaries. Endoscopic mucosal resection (EMR) was performed. Histological
      examination of the specimen revealed the lengthened gastric foveolae in the
      superficial portion and tight sheet of foamy histiocytes in the lamina propria.
      Diagnosis of gastric hyperplastic polyp with proliferation of xanthoma cells was
      made. There was no evidence of malignancy. It is necessary to know that a gastric
      hyperplastic polyp may associate with gastric xanthoma, although such association
      is very rare.

PMID- 20029645
TI  - Drainage or packing of the sella? Transsphenoidal surgery for primary pituitary
      abscess: report of two cases.
AB  - The detailed surgical procedure of the transsphenoidal surgery for pituitary
      abscess has scarcely been described previously because it is a very rare clinical
      entity. The authors reported two cases of primary pituitary abscess. In case 1,
      the anterior wall of the sella turcica was reconstructed with the vomer bone
      after irrigating the abscess cavity, but the sella was not packed by fat for fear
      of the persistent infection by devascularized tissues. This led to the
      postoperative meningocele, the cerebrospinal fluid leak, and bacterial meningitis
      despite the successful abscess drainage. In case 2, tight sellar packing and
      reconstruction of the sellar wall were performed to avoid these postoperative
      complications, which resulted in complete drainage and uneventful postoperative
      course. Although accumulation of more cases is obviously needed to establish the
      definitive surgical technique in pituitary abscess surgery, our experience might
      suggest that packing of the sella is not impeditive for postoperative sufficient
      drainage.

PMID- 20029646
TI  - Enhanced Interaction between Warfarin and High-Dose Ketoconazole: A Case Report.
AB  - This case describes the increased anticoagulation effect associated with the use
      of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic
      valve replacement was prescribed high-dose ketoconazole and hydrocortisone for
      the treatment of prostate cancer. Despite lowering the warfarin dosage by 35%
      during the start of high dose ketoconazole, an additional dose reduction was
      required subsequently when the INR rose from 2.62 to 3.82 within nine days. After
      a total dose reduction of 43%, the INR returned to therapeutic range within two
      weeks. The Naranjo probability scale revealed a probable adverse reaction of
      increased anticoagulant effect associated with high dose ketoconazole. Due to the
      inhibition of warfarin metabolism by ketoconazole, patients taking high dose
      ketoconazole concomitantly with warfarin may need their warfarin dosage reduced
      by more than is currently recommended, as well as receive more frequent INR
      monitoring to avoid over anticoagulation.

PMID- 20029647
TI  - Congenital eye malformations associated with extensive periocular neural crest
      apoptosis after influenza B virus infection during early embryogenesis.
AB  - PURPOSE: Congenital eye malformations are a leading cause of blindness in
      children. Influenza virus infections prevail worldwide and have been implicated
      in congenital defects. Infections acquired during gestation may disrupt eye
      morphogenesis. We investigated the effects of influenza B virus infection on eye
      malformations during early embryogenesis. METHODS: Chick embryos were exposed to
      influenza B virus at Hamburger-Hamilton stage 9. Maternal infection was conducted
      by exposing pregnant ICR mice to influenza B virus at the embryonic gestation
      stage E 5.0. After infection, virus RNA distribution was detected by in situ
      hybridization at various developmental stages. The distribution of periocular
      neural crest cells and the extent of apoptosis were examined by
      immunohistochemical staining, in correlation with eye malformations. RESULTS:
      Microphthalmos and anophthalmos, together with neural tube defects, were found in
      the chick and mouse embryos following the infections. The viral RNA was detected
      in the head neuroepithelium, optic vesicle, periocular mesenchyme, and the
      forming ventricles of the developing brain. Immunohistochemical staining revealed
      aberrant neural crest distribution and extensive apoptosis in the head surface
      ectoderm, periocular mesenchyme, and optic vesicle in the chick embryos.
      Furthermore, transplacental infection was confirmed by the presence of viral RNA
      in the mouse fetuses, with eye and neural tube defects similar to those found in
      the chick embryos after experimental infections. CONCLUSIONS: Influenza B virus
      may act as a teratogen to cause aberrant periocular neural crest cell
      contribution to eye development and extensive apoptosis, resulting in congenital
      eye malformations.

PMID- 20029648
TI  - Trimethylamine N-oxide alleviates the severe aggregation and ER stress caused by
      G98R alphaA-crystallin.
AB  - PURPOSE: Crystallins are major functional and structural proteins in mammalian
      lens. Their expression, distribution, and protein-protein interaction affect lens
      development and fiber cell differentiation. Mutated crystallins lead to
      structural and functional changes of lens structure and could lead to opacity
      formation and cataract development. The purpose of this study was to investigate
      the biological effects of the cataract-causing G98R mutation on the alphaA
      crystallin (CRYAA) protein and to test the capability of chemical chaperone
      trimethylamine N-oxide (TMAO) to reverse such effects. METHODS: Myc/His-tagged,
      human, full-length, wild-type (WT) or G98R CRYAA was expressed in human lens
      epithelial B3 cells and treated or not treated with TMAO. Triton X-100 (Tx)
      solubility and cellular localization of CRYAA were examined by western blotting
      and confocal immunofluorescence, respectively. Ubiquitin proteasome-associated
      degradation was assayed by MG132 treatment. Endoplasmic reticulum (ER) stress,
      unfolded protein response, and apoptosis were analyzed by the expression of
      phosphorylated protein kinase-like ER-kinase, binding immunoglobulin protein
      (BiP), C/EBP homologous protein/growth arrest and DNA damage-inducible gene 153
      (CHOP/GADD153), and caspase-3 and immunocytochemistry. Changes in heat shock and
      stress signaling were investigated. RESULTS: When transfected in lens epithelial
      B3 cells, unlike WT CRYAA located in the cytoplasm, the G98R CRYAA mutant formed
      aggregates inside the ER and the protein was predominantly Tx-insoluble. ER
      stress was induced by G98R CRYAA expression, and cells underwent apoptosis, as
      shown by a more frequent appearance of fragmented nuclei. Treatment with TMAO
      reduced Tx-insoluble mutant protein in time- and dose-dependent manners. Other
      chemical chaperones, 4-phenylbutyric acid, dimethysulfoxide, and glycerol, were
      much less effective than TMAO. ER-associated aggregates were reduced after TMAO
      treatment, and the protein was degraded through the ubiquitin-proteasome pathway.
      This alleviated ER stress and resulted in less apoptosis. Moreover, TMAO
      treatment induced a moderate upregulation of heat shock protein 70, indicating
      its effect on heat-shock response to modulate protein folding and assembly. No
      change was found for nontransfected cells after TMAO treatment. CONCLUSION: The
      natural osmolyte and chemical chaperone TMAO reduced the aggregation of G98R
      CRYAA. This alleviated ER stress and rescued the affected cells from apoptosis.
      Our results showed that the chemical chaperone reduces mutant CRYAA aggregates in
      lens cells. We suggest a potential chemical-based strategy to reduce lens opacity
      formation.

PMID- 20029649
TI  - Outcome of ABCA4 microarray screening in routine clinical practice.
AB  - PURPOSE: To retrospectively analyze the clinical characteristics of patients who
      were screened for mutations with the ATP-binding cassette transporter gene ABCA4
      (ABCA4) microarray in a routine clinical DNA diagnostics setting. METHODS: We
      performed a retrospective analysis of the medical charts of 65 patients who
      underwent an ABCA4 microarray screening between the years 2002 and 2006. An
      additional denaturing gradient gel electrophoresis (DGGE) was performed in these
      patients if less than two mutations were found with the microarray. We included
      all patients who were suspected of autosomal recessive Stargardt disease (STGD1),
      autosomal recessive cone-rod dystrophy (arCRD), or autosomal recessive retinitis
      pigmentosa at the time of microarray request. After a retrospective analysis of
      the clinical characteristics, the patients who were suspected of STGD1 were
      categorized as having either a typical or atypical form of STGD1, according to
      the age at onset, fundus appearance, fluorescein angiography, and
      electroretinography. The occurrence of typical clinical features for STGD1 was
      compared between patients with different numbers of discovered mutations.
      RESULTS: Of the 44 patients who were suspected of STGD1, 26 patients (59%) had
      sufficient data available for a classification in either typical (six patients;
      23%) or atypical (20 patients; 77%) STGD1. In the suspected STGD1 group, 59% of
      all expected pathogenic alleles were found with the ABCA4 microarray. DGGE led to
      the finding of 12 more mutations, resulting in an overall detection rate of 73%.
      Thirty-one percent of patients with two or three discovered ABCA4 mutations met
      all typical STGD1 criteria. An age at onset younger than 25 years and a dark
      choroid on fluorescein angiography were the most predictive clinical features to
      find ABCA4 mutations in patients suspected of STGD1. In 18 patients suspected of
      arCRD, microarray screening detected 22% of the possible pathogenic alleles.
      CONCLUSIONS: In addition to confirmation of the diagnosis in typical STGD1, ABCA4
      microarray screening is usually requested in daily clinical practice to
      strengthen the diagnosis when the disease is atypical. This study supports the
      view that the efficiency and accuracy of ABCA4 microarray screening are directly
      dependent upon the clinical features of the patients who are screened.

PMID- 20029652
TI  - Changes in plasma IL-6, plasma VEGF and serum YKL-40 during Treatment with
      Etanercept and Methotrexate or Etanercept alone in Patients with Active
      Rheumatoid Arthritis Despite Methotrexate Therapy.
AB  - Changes in plasma IL-6, plasma VEGF and serum YKL-40 were determined in
      rheumatoid arthritis (RA) patients during treatment with etanercept alone or in
      combination with methotrexate. Twenty-five patients with active RA (DAS28 >/=
      3.2) were randomized to receive etanercept (25 mg sc. biweekly) plus methotrexate
      (n = 12) or etanercept alone (n = 13). Plasma IL-6, plasma VEGF and serum YKL-40
      were determined by ELISA. The 3 biomarkers and DAS28 scores were evaluated at
      baseline and after 4, 8, 12 and 16 weeks of treatment. At inclusion all patients
      had significantly (p < 0.001) elevated plasma IL-6, plasma VEGF and serum YKL-40
      compared to healthy subjects. Eighteen patients responded to treatment (pooled
      data from both treatment groups), and they had significant (p < 0.05 to p <
      0.001) decreases in plasma IL-6, plasma VEGF, serum YKL-40, ESR and DAS28 after 4
      weeks of treatment and throughout the study (except serum YKL-40 at week 16).
      Plasma IL-6 showed the largest reductions. Non-responders had unchanged
      biomarkers. At week 16 the patients with DAS28 < 3.2 had lower levels compared to
      baseline values in plasma IL-6 (p = 0.005), plasma VEGF (p = 0.014), and ESR (p =
      0.024).Plasma IL-6, plasma VEGF and serum YKL-40, which reflect different aspects
      of the inflammatory process, may provide useful information regarding early
      differentiation of responders from non-responders.

PMID- 20029651
TI  - Biomarkers of adiponectin: plasma protein variation and genomic DNA
      polymorphisms.
AB  - Adiponectin is secreted by white adipose tissue and exists as the most abundant
      adipokine in the human plasma. Recent research has indicated that plasma
      adiponectin levels are inversely correlated with body mass index (BMI) and
      insulin resistance. Reduction of plasma adiponectin levels is commonly observed
      in the patients with type 2 diabetes (T2D) and/or in those who are obese in
      comparison with healthy control individuals. The adiponectin (AdipoQ) gene has a
      moderate linkage disequilibrium (LD), but two small LD blocks are observed,
      respectively, in the promoter region and the boundary of exon 2-intron 2. Genetic
      association studies have demonstrated that single nucleotide polymorphisms (SNPs)
      +45G15G(T/G) in exon 2 and +276G/T in intron 2 of the AdipoQ gene confer the risk
      susceptibility to the development of T2D, obesity and diabetic nephropathy (DN).
      The SNPs in the promoter region, including -11426A/G, -11377C/G and -11391G/A,
      are found to be associated with T2D and DN. Recent research has indicated that
      the promoter polymorphisms interfere with the AdipoQ promoter activity. The
      haplotypes constructed by the promoter polymorphisms and SNP +276G/T in intron 2
      are associated with circulating adiponectin levels. This review summarises
      genetic and pathophysiological relevancies of adiponectin and discusses about the
      biomarkers of adiponectin plasma protein variation and genomic DNA polymorphisms.

PMID- 20029650
TI  - Biomarker Validation for Aging: Lessons from mtDNA Heteroplasmy Analyses in Early
      Cancer Detection.
AB  - The anticipated biological and clinical utility of biomarkers has attracted
      significant interest recently. Aging and early cancer detection represent areas
      active in the search for predictive and prognostic biomarkers. While applications
      differ, overlapping biological features, analytical technologies and specific
      biomarker analytes bear comparison. Mitochondrial DNA (mtDNA) as a biomarker in
      both biological models has been evaluated. However, it remains unclear whether
      mtDNA changes in aging and cancer represent biological relationships that are
      causal, incidental, or a combination of both. This article focuses on evaluation
      of mtDNA-based biomarkers, emerging strategies for quantitating mtDNA admixtures,
      and how current understanding of mtDNA in aging and cancer evolves with
      introduction of new technologies. Whether for cancer or aging, lessons from mtDNA
      based biomarker evaluations are several. Biological systems are inherently
      dynamic and heterogeneous. Detection limits for mtDNA sequencing technologies
      differ among methods for low-level DNA sequence admixtures in healthy and
      diseased states. Performance metrics of analytical mtDNA technology should be
      validated prior to application in heterogeneous biologically-based systems.
      Critical in evaluating biomarker performance is the ability to distinguish
      measurement system variance from inherent biological variance, because it is
      within the latter that background healthy variability as well as high-value,
      disease-specific information reside.

PMID- 20029653
TI  - Decreased Serum Hepatocyte Growth Factor (HGF) in Autistic Children with Severe
      Gastrointestinal Disease.
AB  - AIM: To assess serum Hepatocyte Growth Factor (HGF) levels in autistic children
      with severe gastrointestinal (GI) disease and to test the hypothesis that there
      is a relationship between GI pathology and HGF concentration. SUBJECTS AND
      METHODS: Serum from 29 autistic children with chronic digestive disease (symptoms
      for a minimum of 6-12 months), most with ileo-colonic lymphoid nodular
      hyperplasia (LNH-markedly enlarged lymphoid nodules) and inflammation of the
      colorectum, small bowel and/or stomach), and 31 controls (11 age matched autistic
      children with no GI disease, 11 age matched non autistic children without GI
      disease and 9 age matched non autistic children with GI disease) were tested for
      HGF using ELISAs. HGF concentration of autistic children with GI disease was
      compared to GI disease severity. RESULTS: Autistic children with GI disease had
      significantly lower serum levels of HGF compared to controls (autistic without GI
      disease; p = 0.0005, non autistic with no GI disease; p = 0.0001, and non
      autistic with GI disease; p = 0.001). Collectively, all autistic children had
      significantly lower HGF levels when compared to non autistic children (p <
      0.0001). We did not find any relationship between severity of GI disease and HGF
      concentration in autistic children with GI disease. DISCUSSION: These results
      suggest an association between HGF serum levels and the presence of GI disease in
      autistic children and explain a potential functional connection between the Met
      gene and autism. The concentration of serum HGF may be a useful biomarker for
      autistic children, especially those with severe GI disease.

PMID- 20029654
TI  - An optimal protocol to analyze the rat spinal cord proteome.
AB  - Since the function of the spinal cord depends on the proteins found there, better
      defing the normal Spinal Cord Proteome is an important and challenging task.
      Although brain and cerebrospinal fluid samples from patients with different
      central nervous system (CNS) disorders have been studied, a thorough examination
      of specific spinal cord proteins and the changes induced by injury or associated
      to conditions such as neurodegeneration, spasticity and neuropathies has yet to
      be performed. In the present study, we aimed to describe total protein content in
      the spinal cord of healthy rats, employing different proteomics tools.
      Accordingly, we have developed a fast, easy, and reproducible sequential protocol
      for protein extraction from rat spinal cords. We employed conventional two
      dimensional electrophoresis (2DE) in different pH ranges (eg. 4-7, 3-11 NL)
      combined with identification by mass spectrometry (MALDI-TOF/TOF), as well as
      first dimension protein separation combined with Liquid Chromatography Mass
      Spectrometry/Mass Spectrometry (LC-MS/MS) to maximise the benefits of this
      technology. The value of these techniques is demonstrated here by the
      identification of several proteins known to be associated with neuroglial
      structures, neurotransmission, cell survival and nerve growth in the central
      nervous system. Furthermore this study identified many spinal proteins that have
      not previously been described in the literature and which may play an important
      role as either sensitive biomarkers of dysfunction or of recovery after Spinal
      Cord Injury.

PMID- 20029655
TI  - Association of tumor necrosis factor alpha gene polymorphism G-308A with
      pseudoexfoliative glaucoma in the Pakistani population.
AB  - PURPOSE: The purpose of the present study was to determine the role of the tumor
      necrosis factor alpha (TNF-alpha) gene polymorphism G-308A and total serum
      immunoglobulin E (TsIgE) levels in the onset of pseudoexfoliation glaucoma (PEXG)
      in Pakistani patients. METHODS: The TNF-alpha polymorphism G-308A was analyzed in
      122 patients with PEXG and 126 healthy unrelated controls by using polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP). TsIgE
      levels were determined by solid-phase enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The AA and GA genotypes were strongly associated with PEXG (p<0.001),
      with an odds ratio (OR) of 0.07 (95% confidence interval [CI]=0.02-0.27) and 0.24
      (95% CI=0.12-0.51), respectively, while the GG genotype was found at a higher
      frequency in controls as compared to patients (p<0.001) OR=8.95 (95% CI=4.55
      17.81). No significant difference was found in TsIgE levels of both patients and
      controls (p=0.86). CONCLUSION: The present study concludes that the TNF-alpha
      polymorphism G-308A is strongly associated with PEXG. To our knowledge this is
      the first study in southeast Asia which demonstrates a strong association of a
      TNF-alpha polymorphism with PEXG.

PMID- 20029656
TI  - Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus.
AB  - PURPOSE: Alterations in collagen type IV, alpha-3 (COL4A3) and collagen type IV,
      alpha-4 (COL4A4) genes may be responsible for a decrease in collagen types I and
      III, a feature often detected in keratoconus (KC). To evaluate the significance
      of alterations in COL4A3 and COL4A4 genes in KC patients, we screened both genes
      and estimated the significance of polymorphisms in Slovenian patients with KC.
      METHODS: The study included 104 unrelated patients with KC and 157 healthy blood
      donors. Diagnosis was established by clinical examination, electronic
      refractometry, and keratometry. DNA was extracted from blood, and gene exons were
      amplified by PCR. Non-isotopic high-resolution single-stranded conformation
      analysis (SSCA) was used to screen COL4A3 and COL4A4 genes, and migration shifts
      detected by SSCA were subsequently sequenced. For statistical evaluation, control
      blood donors were chosen according to age, sex, and not having blood
      relationship. Neither patients nor control blood donors chosen for statistical
      analysis were in blood relationship. We used Fisher's exact test for statistical
      evaluation, with p<0.05 considered significant. RESULTS: We detected eight
      polymorphisms in the COL4A3 gene and six in the COL4A4 gene. Allele differences
      in D326Y in COL4A3 and M1237V and F1644F in COL4A4 are significantly distinctive
      of KC patients (Fisher's exact test, p<0.05). When analyzing different genotypes
      under three models (dominant, recessive, and additive), we established that
      P141L, D326Y, and G895G in COL4A3 and P482S, M1327V, V1516V, and F1644F in COL4A4
      have significant differences in genotype distribution between KC patients and the
      control group. CONCLUSIONS: This is the first mutational screening of COL4A3 and
      COL4A4 genes in KC patients to establish the status of these genes and compare
      them to a control population. Analysis of COL4A3 and COL4A4 revealed no mutations
      related to KC patients, but specific genotypes of seven previously described
      polymorphisms are significantly associated with KC under dominant, recessive, or
      additive models. Differences in the expression of type IV collagen in previously
      published data about chromosomal instabilities in the regions in which the
      analyzed genes were mapped and our data indicate a probability that some of the
      polymorphisms we detected could be related to KC.

PMID- 20029657
TI  - Can reactive school closures help critical care provision during the current
      influenza pandemic?
AB  - Although the current H1N1 influenza strain is now considered to be relatively
      mild, it still has the potential to place a serious burden on health services.
      The closure of schools has been postulated as a means of reducing transmission
      between children and hence reducing the number of cases at the peak of an
      epidemic; however if instigated nationally such a policy has severe economic
      costs. Reactive short-duration closure of schools in regions where health
      services are close to capacity offers a potential compromise, but it is unclear
      over what spatial scale and timeframe closures would need to be made to have a
      substantial impact. Here, using detailed geographic information for England, we
      assess how localized school closures could alleviate the burden on hospital
      intensive care units (ICUs) that are reaching capacity. We show that, for a range
      of epidemiologically plausible assumptions, considerable local coordination of
      school closures is needed to achieve a substantial reduction in the number of
      hospitals that are over capacity at the epidemic peak. The heterogeneity in
      demand per hospital means that even widespread school closures are unlikely to
      impact on whether demand will exceed capacity for many hospital ICUs. These
      results re-enforce the UK policy of not utilising school closures as a control
      mechanism, but have far wider international public-health implications. The
      spatial heterogeneities in both population density and hospital capacity that
      give rise to our results are present in many Northern Hemisphere countries where
      a second wave of influenza is predicted this autumn and winter. This leads us to
      believe that even widespread reactive school closures are unlikely to eliminate
      problems of demand exceeding local capacity in many regions.

PMID- 20029658
TI  - Improving the diagnostic efficiency of H1N1 2009 pandemic flu: analysis of
      predictive clinical signs through a prospective cohort.
AB  - In late June 2009, we set up a dedicated flu-like illness outpatient consultation
      in the Infectious Diseases and Tropical Medicine department of Marseille
      university hospital to detect the new A/H1N1 pandemic influenza and to contain
      efficiently the A/H1N1 infected patients. For 3 months, we compiled data
      corresponding to a total of 307 patients who presented with a flu-like syndrome.
      31 of them were positive for H1N1 pandemic flu through real-time RT-PCR (rRT
      PCR); among them, 19 were positive for a rapid influenza detection test (RIDT).
      We report here the significant clinical characteristics of A/H1N1 pandemic flu
      patients compared with other flu-like illnesses, which were used to improve the
      predictive value of the diagnosis in the current epidemiological situation. We
      found that regardless of the prevalence of A/H1N1 positive cases in the suspected
      patients, the absence of cough rejects the diagnosis of A/H1N1 infection in 100%
      of cases. Among patients referred for flu-like illness, those with cough should
      be tested for A/H1N1 by RIDT. In the current situation, the PPV and NPV of RIDT
      for H1N1 reached 90.5% and 95.8 %, respectively. It is important to notice that
      the 2 RIDT-positive that were negative for H1N1 were seasonal H3N2 influenza
      indicating that specificity and PPV of RIDT for all influenza was 100%.
      Therefore, positive RIDT does not require rRT-PCR confirmatory test. Only
      negative RIDT should be tested with rRT-PCR assay. Respecting this algorithm
      would have saved up to 70,000 Euros ( 100.000 USD) for the 307 patients and would
      have resulted in a significant gain of time to transmit the laboratory results to
      the clinical ward.

PMID- 20029660
TI  - Antiviral usage for H1N1 treatment: pros, cons and an argument for broader
      prescribing guidelines in the United States.
AB  - Current CDC guidelines for antiviral treatment of people with influenza like
      illness (ILI) effectively discourage treatment of people with no underlying
      medical conditions unless they exhibit severe symptoms, such as evidence of lower
      respiratory tract infection or clinical deterioration. This guidance is unlike
      that provided by some other countries, which allow for treatment of most
      moderately symptomatic individuals. We examine evidence for benefits of antiviral
      usage for influenza treatment, including its relation to severe outcomes for the
      current pandemic H1N1 strain. We also discuss some of the potential cons of
      antiviral usage. In the current situation in the US, with an elevated and
      evidently growing burden of influenza hospitalizations and mortality, a high
      percentage of individuals infected with influenza (with almost all of those
      carrying the H1N1pdm strain) among those who exhibit ILI and get tested for
      influenza virus, very low levels of antiviral resistance and little time left for
      antiviral resistance to take off before large quantities of vaccine become
      available, we think it is worthwhile to consider a revision to the current
      antiviral usage recommendations, such that physicians would be encouraged to
      consider prescribing antivirals to individuals with moderate to severe symptoms
      who present for treatment.

PMID- 20029659
TI  - Targeted vs. systematic early antiviral treatment against A(H1N1)v influenza with
      neuraminidase inhibitors in patients with influenza-like symptoms: clinical and
      economic impact.
AB  - Capitalizing on available data, we used a decision model to estimate the clinical
      and economic outcomes associated with early initiation of treatment with
      neuraminidase inhibitors in all patients with influenza-like illnesses ( ILI )
      (systematic strategy) vs. only those at high risk of complications (targeted
      strategy). Systematic treatment of ILI during an A(H1N1)v influenza epidemic wave
      is both effective and cost-effective. Patients who present to care with ILI
      during an A(H1N1)v influenza epidemic wave should initiate treatment with
      neuraminidase inhibitors, regardless of risk status. Administering neuraminidase
      inhibitors between epidemic waves, when the probability of influenza is low, is
      less effective and cost-effective.

PMID- 20029661
TI  - Rapid development of an efficacious swine vaccine for novel H1N1.
AB  - Recombinant hemagglutinin (HA) from a novel H1N1 influenza strain was produced
      using an alphavirus replicon expression system. The recombinant HA vaccine was
      produced more rapidly than traditional vaccines, and was evaluated as a swine
      vaccine candidate at different doses in a challenge model utilizing the
      homologous influenza A/California/04/2009 (H1N1) strain. Vaccinated animals
      showed significantly higher specific antibody response, reduced lung lesions and
      viral shedding, and higher average daily gain when compared to non-vaccinated
      control animals. These data demonstrate that the swine vaccine candidate was
      efficacious at all of the evaluated doses.

PMID- 20029662
TI  - Mining the NCBI influenza sequence database: adaptive grouping of BLAST results
      using precalculated neighbor indexing.
AB  - The Influenza Virus Resource and other Virus Variation Resources at NCBI provide
      enhanced visualization web tools for exploratory analysis for influenza sequence
      data. Despite the improvements in data analysis, the initial data retrieval
      remains unsophisticated, frequently producing huge and imbalanced datasets due to
      the large number of identical and nearly-identical sequences in the database.We
      propose a data mining algorithm to organize reported sequences into groups based
      on their relatedness to the query sequence and to each other. The algorithm uses
      BLAST to find database sequences related to the query. Neighbor lists
      precalculated from pairwise BLAST alignments between database sequences are used
      to organize results in groups of nearly-identical and strongly related sequences.
      We propose to use a non-symmetric dissimilarity measure well crafted for dealing
      with sequences of different length (fragments). A balanced and representative
      data set produced by this tool can be used for further analysis, i.e. multiple
      sequence alignment and phylogenetic trees. The algorithm is implemented for
      protein coding sequences and is being integrated with the NCBI Influenza Virus
      Resource.

PMID- 20029663
TI  - Quantifying the transmissibility of human influenza and its seasonal variation in
      temperate regions.
AB  - Seasonal influenza has considerable impact around the world, both economically
      and in mortality among risk groups. The long term patterns of disease are hard to
      capture with simple models, while the interplay of epidemiological processes with
      antigenic evolution makes detailed modelling difficult and computationally
      intensive. We identify a number of characteristic features of flu incidence time
      series in temperate regions, including ranges of annual attack rates and outbreak
      durations. We construct pseudo-likelihoods to capture these characteristic
      features and examine the ability of a collection of simple models to reproduce
      them under seasonal variation in transmission. Results indicate that an age
      structured model with non-random mixing and co-circulating strains are both
      required to match time series data. The extent of matching behaviour also serves
      to define informative ranges for parameters governing essential dynamics. Our
      work gives estimates of the seasonal peak basic reproduction, R0, in the range
      1.7-2.1, with the degree of seasonal variation having limited impact of these
      estimates. We find that it is only really possible to estimate a lower bound on
      the degree of seasonal variation in influenza transmissibility, namely that
      transmissibility in the low transmission season may be only 5-10% less than the
      peak value. These results give some insight into the extent to which
      transmissibility of the H1N1pdm pandemic virus may increase in Northern
      Hemisphere temperate countries in winter 2009. We find that the timescale for
      waning of immunity to current circulating seasonal influenza strain is between 4
      and 8 years, consistent with studies of the antigenic variation of influenza, and
      that inter-subtype cross-immunity is restricted to low levels.

PMID- 20029664
TI  - The early diversification of influenza A/H1N1pdm.
AB  - Background Since its initial detection in April 2009, the A/H1N1pdm influenza
      virus has spread rapidly in humans, with over 5,700 human deaths. However, little
      is known about the evolutionary dynamics of H1N1pdm and its geographic and
      temporal diversification.Methods Phylogenetic analysis was conducted upon the
      concatenated coding regions of whole-genome sequences from 290 H1N1pdm isolates
      sampled globally between April 1 - July 9, 2009, including relatively large
      samples from the US states of Wisconsin and New York. Results At least 7
      phylogenetically distinct viral clades have disseminated globally and co
      circulated in localities that experienced multiple introductions of H1N1pdm. The
      epidemics in New York and Wisconsin were dominated by two different clades, both
      phylogenetically distinct from the viruses first identified in California and
      Mexico, suggesting an important role for founder effects in determining local
      viral population structures. Conclusions Determining the global diversity of
      H1N1pdm is central to understanding the evolution and spatial spread of the
      current pandemic, and to predict its future impact on human populations. Our
      results indicate that H1N1pdm has already diversified into distinct viral
      lineages with defined spatial patterns.

PMID- 20029665
TI  - Optimizing tactics for use of the U.S. Antiviral Strategic National Stockpile for
      Pandemic (H1N1) Influenza, 2009.
AB  - Public health agencies across the globe are working to mitigate the impact of the
      2009 pandemic caused by swine-origin influenza A (H1N1) virus. Prior to the large
      scale distribution of an effective vaccine, the primary modes of control have
      included careful surveillance, social distancing and hygiene measures, strategic
      school closures, other community measures, and the prudent use of antiviral
      medications to prevent infection (prophylaxis) or reduce the severity and
      duration of symptoms (treatment). Here, we use mathematical models to determine
      the optimal geo-temporal tactics for distributing the U.S. strategic national
      stockpile of antivirals for treatment of infected cases during the early stages
      of a pandemic, prior to the wide availability of vaccines.We present a versatile
      optimization method for efficiently searching large sets of public health
      intervention strategies, and apply it to evaluating tactics for distributing
      antiviral medications from the U.S. Strategic National Stockpile (SNS). We
      implemented the algorithm on a network model of H1N1 transmission within and
      among U.S. cities to project the epidemiological impacts of antiviral stockpile
      distribution schedules and priorities. The resulting optimized strategies
      critically depend on the rates of antiviral uptake and wastage (through
      misallocation or loss). And while a surprisingly simple pro rata distribution
      schedule is competitive with the optimized strategies across a wide range of
      uptake and wastage, other equally simple policies perform poorly.Even as
      vaccination campaigns get underway worldwide, antiviral medications continue to
      play a critical in reducing H1N1-associated morbidity and mortality. If efforts
      are made to increase the fraction of cases treated promptly with antivirals above
      current levels, our model suggests that optimal use of the antiviral component of
      the Strategic National Stockpile may appreciably slow the transmission of H1N1
      during fall 2009, thereby improving the impact of targeted vaccination. A more
      aggressive optimized antiviral strategy of this type may prove critical to
      mitigating future flu pandemics, but may increase the risk of antiviral
      resistance.

PMID- 20029666
TI  - Public preparedness guidance for a severe influenza pandemic in different
      countries: a qualitative assessment and critical overview.
AB  - During a severe influenza pandemic individuals and families can, by following
      well-directed and scientifically-based measures, not only benefit themselves but
      also play an effective role in reducing transmission rates and the burden on
      public services. Such guidelines should be provided as clearly and
      comprehensively as possible by official sources. Here we examine the official
      recommendations issued by 10 countries to prepare their citizens for a severe
      pandemic. We have found the presence of hazardous guidelines - as the advice to
      personally visit a health center at the earliest symptoms - and shortage of
      practical advices for home isolation, business preparation and treatment to be
      widespread. Our review shows that, while many positive recommendations were
      provided, the set of recommendations issued by most countries was not
      comprehensive enough for severe influenza scenarios. This is a situation that
      needs revision.

PMID- 20029667
TI  - Estimate of Novel Influenza A/H1N1 cases in Mexico at the early stage of the
      pandemic with a spatially structured epidemic model.
AB  - Determining the number of cases in an epidemic is fundamental to properly
      evaluate several disease features of high relevance for public health policies
      such as mortality, morbidity or hospitalization rates. Surveillance efforts are
      however incomplete especially at the early stage of an outbreak due to the
      ongoing learning process about the disease characteristics. An example of this is
      represented by the number of H1N1 influenza cases in Mexico during the first
      months of the current pandemic. Several estimates using backtrack calculation
      based on imported cases from Mexico in other countries point out that the actual
      number of cases was likely orders of magnitude larger than the number of
      confirmed cases. Realistic computational models fed with the best available
      estimates of the basic disease parameters can provide an ab-initio calculation of
      the number of cases in Mexico as other countries. Here we use the Global Epidemic
      and Mobility (GLEaM) model to obtain estimates of the size of the epidemic in
      Mexico as well as of imported cases at the end of April and beginning of May. We
      find that the reference range for the number of cases in Mexico on April 30th is
      121,000 to 1,394,000 in good agreement with the recent estimates by Lipsitch et
      al. [M. Lipsitch, PloS One 4:e6895 (2009)]. The number of imported cases from
      Mexico in several countries is found to be in good agreement with the
      surveillance data.

PMID- 20029669
TI  - H1N1 vaccination and adults with underlying health conditions in the US.
AB  - 65% of fatalities from pH1N1 infections in a large US case series occur in adults
      with underlying health conditions other than pregnancy, but it appears that only
      relatively few high-risk adults will get vaccinated during the fall wave of pH1N1
      transmission. There are several reasons for this problem; the most important is
      vaccine shortage. High risk adults (other than pregnant women) were not part of
      the initial, narrow priority cohort which included pregnant women and children
      ages 0.5-4; this is despite the fact that some of those high risk groups, such as
      immunosuppressed adults and possibly individuals with neurological disorders,
      have a relative risk for fatality (per capita) higher than pregnant women, and
      over 28-fold higher than healthy children under the age of 4. With more vaccine
      becoming available than needed in the initial priority cohort, a broader group
      which includes high risk adults and individuals under 24 becomes eligible for
      vaccine in many locations. Nonetheless, due to continuing high demand, high-risk
      adults face competition for vaccine from healthy individuals under 24;
      additionally, some locations specifically prioritize school students over high
      risk adults. Finally, there is an issue of awareness and a shortage of specific
      channels that target high risk adults other than pregnant women and facilitate
      vaccine distribution among them in the US.

PMID- 20029668
TI  - The Early Transmission Dynamics of H1N1pdm Influenza in the United Kingdom.
AB  - We analyzed data on all laboratory-confirmed cases of H1N1pdm influenza in the UK
      to 10th June 2009 to estimate epidemiological characteristics. We estimated a
      mean incubation period of 2.05 days and serial interval of 2.5 days with
      infectivity peaking close to onset of symptoms. Transmission was initially
      sporadic but increased from mid-May in England and from early June in Scotland.
      We estimated 37% of transmission occurred in schools, 24% in households, 28%
      through travel abroad and the remainder in the wider community. Children under 16
      were more susceptible to infection in the household (adjusted OR 5.80, 95% CI
      2.99-11.82). Treatment with oseltamivir plus widespread use of prophylaxis
      significantly reduced transmission (estimated reduction 16%). Households not
      receiving oseltamivir within 3 days of symptom onset in the index case had
      significantly increased secondary attack rates (adjusted OR 3.42, 95% CI 1.51
      8.55).

PMID- 20029670
TI  - Modeling the critical care demand and antibiotics resources needed during the
      Fall 2009 wave of influenza A(H1N1) pandemic.
AB  - While the H1N1 pandemic is reaching high levels of influenza activity in the
      Northern Hemisphere, the attention focuses on the ability of national health
      systems to respond to the expected massive influx of additional patients. Given
      the limited capacity of health care providers and hospitals and the limited
      supplies of antibiotics, it is important to predict the potential demand on
      critical care to assist planning for the management of resources and plan for
      additional stockpiling. We develop a disease model that considers the development
      of influenza-associated complications and incorporate it into a global epidemic
      model to assess the expected surge in critical care demands due to viral and
      bacterial pneumonia. Based on the most recent estimates of complication rates, we
      predict the expected peak number of intensive care unit beds and the stockpile of
      antibiotic courses needed for the current pandemic wave. The effects of dynamic
      vaccination campaigns, and of variations of the relative proportion of bacterial
      co-infection in complications and different length of staying in the intensive
      care unit are explored.

PMID- 20029671
TI  - Osteotomy and autograft lengthening for intra-articular malunion of the proximal
      ulna: a case report.
AB  - An osteotomy with interposition of iliac crest bone graft and lengthening of the
      proximal ulna can be used to restore ulnohumeral congruency after a malunited
      comminuted olecranon fracture treated with figure-of-eight tension band wiring.

PMID- 20029672
TI  - Glioblastoma multiforme in the posterior cranial fossa in a patient with
      neurofibromatosis type I.
AB  - Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing
      neoplasms. The most common brain tumors, found in 15%-20% of NF1 patients, are
      hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic
      astrocytomas. These tumors generally have a benign nature. NF1 patients are
      predisposed to a 5-fold increased incidence of high-grade astrocytomas, which are
      usually located in supratentorial regions of the brain. We present an NF1 patient
      who developed a high-grade astrocytoma in the posterior fossa and discuss
      possible pathophysiological mechanisms.

PMID- 20029673
TI  - Renal angiomyolipoma associated with inferior vena cava thrombus.
AB  - A 57-year-old woman was found to have an inferior vena cava involvement of a
      known sinusal angiomyolipoma incompletely resected three years beforehand.
      Intravascular extension into the IVC of angiomyolipoma has rarely been reported.
      We present a new case and reconsider the literature about this uncommon
      complication of a benign renal tumor.

PMID- 20029675
TI  - The heart-brain connection begets cardiovascular psychiatry and neurology.

PMID- 20029674
TI  - Atypical craniosynostosis with torticollis and neurological symptoms: a
      rhombencephalosynapsis sequence.
AB  - Purpose. We describe a case of 3-year-old girl with rhombencephalosynapsis, a
      rare cerebellar anomaly. Patient. A 3-year-old girl was admitted to our hospital
      due to congenital torticollis and asymmetry of face, skull and trunk.
      Craniosynostosis was suspected due to abnormal head shape. 3D-CT revealed closure
      of the sagittal suture without scaphocephalic skull. Due to atypical
      craniosynostosis with neurological symptoms, brain-MRI was performed revealing
      rhombencephalosynapsis. Results. Our patient presented with atypical
      craniosynostosis and balance problems, not typical for scaphocephaly. Operative
      treatment for craniosynotosis was not carried out because the cause of the
      problems was the cerebellum instead of the brain. Conclusions. Therefore, we
      conclude that patients with atypical craniosynostosis should be examined with
      brain-MRI to exclude the intracranial malformations, which 3D-CT does not reveal.
      Without brain-MRI, decision (not) to perform surgery could have been different.

PMID- 20029680
TI  - Calcification-related absorption in thyroid scintigraphy.
AB  - The enhanced absorption of X-rays in calcified structures is a basic prerequisite
      for performing conventional bone radiography. On the other hand, nothing has been
      reported on possible absorption effects of 'calcifications' as frequent findings
      in thyroid nodules or in the sternal bone / sternoclavicular joints. This may be
      caused by the general opinion, that the high energy of 99mTc-photons (140 keV) do
      not make visible absorptions effects very likely. PATIENTS, METHODS: To prove
      possible absorption effects of calcifications on thyroid scintigraphy
      experimentally, effects of calcium absorbers were tested on a technetium flood
      phantom. Furthermore, absorption effects of various calcifications (discs of
      calcium sulphate and calcium carbonate with varying thickness) on normal thyroid
      tissue and autonomous nodules were simulated in a thyroid phantom. CT 130 kV
      images of 46 consecutive patients were checked for presence of retrosternal or
      retroclavicular growth of the thyroid gland and to measure the extent and density
      of the sternal bone and calcified intrathyroidal nodules. In addition, clinical
      cases are presented in which a possible absorption by calcifications seems to be
      likely. RESULTS: Bony structures in front of the thyroid gland or calcified
      intrathyroidal nodules could be seen on CT in 24/46 patients. The mean averaged
      density was 219 Houndsfield units (SD: 89 HU). The quantitative measurements
      using a 99mTc-flood source showed a mean absorption of 4.9%. In a thyroid
      phantom, absorption effects were visible only in 3/20 positions of the calcium
      discs over the thyroid phantom. Focal effects could be better detected in
      situations of only moderate uptake of the surrounding tissue. A dependence of
      absorption and chemistry (sulphate, carbonate) could not be found. CONCLUSION:
      Visible absorption effects caused by sternal bone or thyroid calcifications are
      seldom but potentially able to diminish the visible uptake and should be taken
      into account when interpreting thyroid scintigrams.

PMID- 20029681
TI  - [Chromatographic determination of radiochemical purity - replacement of ITLC SG].
AB  - Thin layer chromatography is well established for quality control of
      radiopharmaceuticals. A convenient and widely used stationary phase are ITLC SG
      strips. However, the Pall Corporation stopped manufacturing of the silica gel
      impregnated glass fibre strips (ITLC SG). Material, Methode: As a replacement we
      tested silicic acid impregnated glass fibre strips from Varian (ITLC SA) and
      sufficient mobile phases. RESULTS: The chromatography with these strips takes two
      to three times longer than with ITLC SG, but it is in an acceptable range. Only
      three mobile phases are necessary to test most of the common in-house made
      radiopharmaceuticals. CONCLUSION: The proposed method is suitable for routinely
      measuring the radiochemical purity of radiophamaceuticals.

PMID- 20029682
TI  - Quantitative analysis of synaptic vesicle release and readily releasable pool
      size in hippocampal neurons.
AB  - In central nervous system only a limited number of vesicles exist in the
      presynaptic terminals. The size and fusion modes of the vesicles were
      particularly important because of their potential impact on neuronal
      communications. Efficient methods were needed to analyze the recycling kinetics
      of synaptic vesicle and the size of readily releasable pool (RRP). In this study,
      fluorescent dyes with different affinity for membranes (FM1-43 with high affinity
      and FM2-10 with low affinity) were used to stain the functional synaptic vesicles
      of cultured hippocampal neurons and the kinetics of vesicle recycling was
      measured. The results showed that the destaining proportion was larger for FM2-10
      than that for FM1-43 during the first trial, while it was greater for FM1-43 than
      FM2-10 during the second and third trials (first round, 93.0%+/-5.9% versus
      57.9%+/-3.5% for FM2-10 and FM1-43, respectively, P<0.0001; second round, 1.4%+/
      3.8% versus 24.0%+/-2.3%, P<0.0001; third round, 2.3%+/-1.6% versus 8.6%+/-1.5%,
      P=0.005). The results indicated that rapid endocytosis existed not only in the
      first round but also occurred when the vesicles were reused. Moreover, Both high
      frequency stimuli and hypertonic sucrose stimuli were used to estimate the RRP
      sizes in the mix cultured hippocampal inhibitory neurons at 13-14 days in vitro
      (DIV). We found that the RRP size estimated by hypertonic sucrose stimuli [(200+/
      23.0) pC] was much larger than that estimated by high-frequency stimuli [(51.1+/
      10.5) pC]. One possible reason for the discrepancies in RRP estimates is that in
      mix cultured conditions, one neuron may receive inputs from several neurons and
      hypertonic sucrose stimuli will cause RRP of all those neurons release, while
      using dual patch recording, only the connection between two neurons was analyzed.
      Thus, to exclude out the impacts of inputs numbers on RRP sizes, it is more
      reasonable to use high-frequency stimuli to estimate the RRP size in mix cultured
      neurons.

PMID- 20029683
TI  - [Dopamine-dependent long-term depression in hippocampus of rat induced by
      exposure to spatial novelty.].
AB  - To study the role of long-term depression (LTD) in the mechanisms of learning and
      memory in hippocampus of rat, recordings were taken from freely moving animals
      that had undergone chronic implantation of a recording electrode in the
      hippocampus CA1 region and a bipolar stimulating electrode in the ipsilateral
      Schaffer collateral-commissural pathway. The recording electrode was inserted 3.8
      mm posterior to bregma and 2.8 mm right of the midline, and the stimulating
      electrode was inserted 4.8 mm posterior to bregma and 3.8 mm right of the midline
      via holes drilled through the skull. The entire assembly was connected with a
      rubber socket on the animal's head and then stabilized with dental cement. The
      correct placement of the electrodes into the hippocampal CA1 area was confirmed
      via electrophysiological criteria and postmortem histological analysis. After 2
      weeks of surgery recovery, the rats were placed in the familiar recording chamber
      for 3 days. The field excitatory postsynaptic potentials (fEPSPs) were evoked by
      stimulating with a square wave constant current pulse of 0.2 ms duration, at a
      frequency of 0.033 Hz and at a stimulation intensity adjusted to given an fEPSP
      amplitude of 50% of the maximum, and the baseline of fEPSPs were recorded for 3
      days in the familiar recording environment at the same time each day. A novelty
      environment that was made of clear Perspex (40 cm x 40 cm x 40 cm) was prepared
      and we examined whether exposure to a novelty spatial environment facilitated the
      expression of activity-dependent persistent decrease in synaptic transmission
      (namely LTD) at CA1 synapses in the rat hippocampus. The results showed that
      brief exposure to a novelty environment for 10 min facilitated the expression of
      LTD in the hippocampal CA1 area under no other exogenous high- or low-frequency
      stimulation protocol. This facilitatory effect was dependent on the activation of
      D1/D5 receptors: the D1/D5 receptors antagonist SCH23390 prevented the decrease
      of synaptic transmission in the hippocampus during the novelty exploration. These
      data provided important evidence that LTD may underlie certain forms of learning
      and memory and that dopamine participates in the synaptic plasticity in the
      process of hippocampal spatial information storage.

PMID- 20029684
TI  - Involvement of nicotinic acetylcholine receptors in amyloid beta-fragment-induced
      intracellular Ca(2+) elevation in cultured rat cortical neurons.
AB  - The amyloid beta-protein (Abeta)-induced disturbance of intracellular calcium
      homeostasis has been regarded as the final route whereby Abeta insults neurons.
      However, the mechanism of Abeta-induced Ca(2+) overloading is still unclear so
      far. Especially, it remains to be clarified whether nicotinic acetylcholine
      receptors (nAChRs) are involved in the Abeta-induced elevation of intracellular
      calcium concentration ([Ca(2+)](i)). In the present study, we observed the
      effects of Abeta fragments 25-35 (Abeta(25-35)) and 31-35 (Abeta(31-35)) on
      [Ca(2+)](i) in primary cultured rat cortical neurons using laser-scanning
      confocal calcium imaging technique, and investigated its probable cholinergic
      mechanism. The results showed that: (1) Both Abeta(25-35) and Abeta(31-35)
      induced similar and significant [Ca(2+)](i) elevation in a concentration
      dependent manner, and no statistical difference was found between the effects of
      both peptides; (2) The reverse peptide of Abeta(31-35), i.e. Abeta(35-31), had no
      effect on [Ca(2+)](i) elevation; (3) Mecamylamine (MCA), a non-specific nAChRs
      antagonist, significantly and dose-dependently blocked the [Ca(2+)](i) elevation
      induced by Abeta(25-35) or Abeta(31-35) (4) Dihydro-beta-erythroidine (D-beta-E),
      a specific alpha4beta2 subtype nAChRs antagonist, also significantly inhibited
      the [Ca(2+)](i) elevation induced by Abeta(25-35) and Abeta(31-35), but the
      effect was weaker than the effect of MCA at the same concentration. These results
      indicate that Abeta(31-35) may be a shorter active sequence in full length of
      Abeta molecule, and the overactivation of nAChRs, including alpha4beta2 subtype,
      may be, at least partly, responsible for the Abeta-induced elevation of
      [Ca(2+)](i) in cultured rat cortical neurons. Thus, the present study suggests a
      new potential target of Abeta in the brain, and provides a new insight into the
      mechanisms by which Abeta impairs the cognitive function in Alzheimer's disease.

PMID- 20029685
TI  - [Intein-mediated F309SfVIII ligation with enhanced secretion of its heavy
      chain.].
AB  - Coagulation factor VIII (fVIII) is a secretion protein and plays a crucial role
      in the coagulation cascade. Hemophilia A resulted from deficiency of fVIII is the
      most common X-linked recessive bleeding disorder. Gene therapy is recognized as
      an attractive strategy for the eventual cure of this disease. However, the gene
      therapy is hampered by the big size of fVIII gene when using the most promising
      gene vectors, adeno-associated virus (AAV) vectors. In this study we explored the
      intein-mediated protein trans-splicing to deliver a Phe(309)-->Ser mutant full
      length fVIII (F309SfVIII) gene by using a dual-vector system. An intein is a
      protein sequence embedded within a precursor protein and can excise itself
      through protein splicing. The F309SfVIII is proven to be beneficial to its
      secretion. The F309SfVIII gene was broken into heavy and light chains before
      Ser(1239) in B domain and fused with the coding sequences of Ssp DnaB intein
      respectively to construct a pair of plasmid vectors by inserting them into the
      pcDNA3.1 vectors. Forty-eight hours after co- or separate transfection of 293
      cells, the co-transfected cell lysate showed an obvious ligated F309SfVIII
      protein band by Western blot with a polyclonal antibody against fVIII. The
      amounts of secreted F309SfVIII protein in culture supernatants and their
      bioactivities were (71+/-9) ng/mL and (0.38+/-0.09) IU/mL determined by ELISA and
      Coatest assay respectively. The supernatant from combined cells with separate
      transfections also displayed lower levels of F309SfVIII antigen and fVIII
      activity [(25+/-6) ng/mL and (0.12+/-0.05) IU/mL], indicating the F309SfVIII
      could be formed by splicing both before and after secretion. The content of
      F309SfVIII heavy chain protein from co-transfected cell supernatant was higher
      than that of intein-fused heavy chain transfection alone [(135+/-10) ng/mL vs
      (37+/-7) ng/mL, P<0.01)]. These data demonstrated that intein could be used as a
      technical strategy in a dual-vector system delivering F309SfVIII gene with
      improved secretion of fVIII providing an alternative approach to circumvent the
      packaging limitation of AAV for F309SfVIII gene transfer, which encourages our
      continuing study in hemophilia A gene therapy in vivo.

PMID- 20029686
TI  - [Construction of eukaryotic expression vector of glucose-regulated protein 75
      gene deletion mutant and its expression in PC12 cells.].
AB  - Glucose-regulated protein 75 (Grp75) binds to p53 and inhibits its nuclear
      translocation, and thus plays a role in cell protection. To investigate whether
      the binding of Grp75 and p53 would influence the viability of cells, we
      constructed the eukaryotic expression vector of Grp75 deletion mutant. The
      deletion mutant gene was obtained by SOE-PCR (gene splicing by overlap extension)
      and then linked to the pcDNA3.0 vector. The constructed specific expression
      vector, pcDNA3.0/Grp75(Delta253-282), was identified by restriction enzymes and
      sequencing. Then we used liposome to transfect the specific vector into PC12
      cells. The stable cell strain PC12/Grp75(Delta253-282)(+) was selected by G418 (1
      mg/mL). Semi-quantitative RT-PCR and Western blot showed that Grp75 mRNA and
      protein expressions in PC12/Grp75(Delta253-282)(+) cells were higher than those
      in PC12 cells. The viability of cells undergoing 0 h, 3 h, 9 h, 18 h and 36 h of
      glucose deprivation respectively was measured by MTT assay. The results showed
      that the cell viability of PC12/Grp75(+) group was significantly higher than that
      of the other two groups, and the cell viability of PC12/Grp75(Delta253-282)(+)
      group was significantly higher than that of the PC12 group (P<0.05). Hoechst33324
      staining was employed to detect cell apoptosis and the results were consistent
      with the MTT assay results. Western blot results indicated that the expression of
      p53 in PC12/Grp75(+) cells was lower than those in the other two groups, which
      might be due to the overexpression of Grp75. These results suggest that the
      protective role of Grp75 is partly associated with its binding to p53. The above
      results suggest that Grp75 deletion mutation could to some extent reduce the
      viability of cells.

PMID- 20029687
TI  - [Relevance of vasoactive intestinal peptide and total bronchial mucin in rat
      lung.].
AB  - Vasoactive intestinal peptide (VIP) is a neuropeptide with potent bronchodilator,
      immunomodulator, and anti-inflammatory properties, and thus has biological
      properties capable of counteracting all major features of the asthmatic response.
      However, the effect of VIP on bronchial mucin secretion remains unclear. In order
      to observe the influence of VIP on bronchial mucin, the present study was
      designed to observe the correlation between VIP and total bronchial mucin changes
      under different time of ozone stress in rat lung. Sixty-four Sprague-Dawley rats
      were used in the experiment. Under different time of ozone stress, VIP content in
      lung homogenate was analyzed by radioimmunoassay, and changes in total bronchial
      mucin in the lung were analyzed by calculating the goblet cell hyperplasia ratio
      and the epithelial cell mucus occupying ratio from the periodic acid-Schiff
      reaction (PAS) staining. The results showed that, at early stage of respiratory
      tract injury, VIP did not change significantly, while the total bronchial mucin
      secretion increased; with the development of damage, the secretion of VIP
      increased by compensation, followed by a decrease in total bronchial mucin; with
      further injury, the numbers of pulmonary endocrine VIP positive nerve fibers and
      endocrine cells decreased, but bronchial mucin volume gradually increased. It is
      concluded that the secretion of VIP is negatively correlated with the secretion
      of bronchial mucin during the development of inflammation.

PMID- 20029688
TI  - [Comparison of the systemic vascular resistance and the correlative factors in
      Han and Korean populations of China.].
AB  - In the present study, the differences in systemic vascular resistance (SVR) and
      the correlated risk factors between Han and Korean residents were investigated. 1
      647 Hans and 876 Koreans from Mudanjiang and Hailin areas of Heilongjiang
      Province were examined with BIOZ Cardio Dynamics Monitor. A series of factors
      were determined, including SVR, systemic vascular resistance index (SVRI),
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), cardiac output (CO), cardiac output index (CI) and heart rate
      (HR). The data were analyzed with SPSS 15.0 statistic software. When SVR/SVRI
      were compared between Han and Korean populations by t-test, it was shown that
      statistic difference existed in the following age and gender groups: (1) For SVR:
      male 41-50, 51-60, and 61-70 (P<0.001), 31-40 (P<0.01), 19-30 (P<0.05) age
      groups; female 15-18, 31-40, 51-60 (P<0.001), 41-50 (P<0.01), and 61-70 (P<0.05)
      age groups; (2) For SVRI, male 41-50, 51-60 (P<0.05) age groups; female 10-14, 51
      60 (P<0.001), 15-18, 31-40 (P<0.01), and 41-50 (P<0.05) age groups. Covariance
      analysis suggests that, excluding the contributions of gender, age and body mass
      index (BMI), the differences in SVR/SVRI between the two populations are still
      significant (P<0.001). Multiple linear regression analysis reveals that SVR
      difference between Han and Korean populations is attributed to MAP, DBP, CI, SBP,
      HR; While SVRI difference between two populations is attributed to MAP, DBP, SBP,
      CI, HR, strongly to weakly, respectively. These results suggest the higher SVR
      and SVRI are possibly correlated with the relatively higher blood pressure of
      Korean, compared with that of Han population.

PMID- 20029689
TI  - [Comparison of cardiac function and expression and activity of myocardial calcium
      regulatory proteins in rabbit systolic and diastolic heart failure models.].
AB  - The aim of the present study is to investigate the differences in cardiac
      function, and the expression and activity of calcium regulatory proteins between
      rabbit systolic heart failure (SHF) and diastolic heart failure (DHF) models. New
      Zealand white rabbits were randomly divided into three groups: sham operation
      (SO) group, DHF group (receiving abdominal aortic constriction) and SHF group
      (receiving aortic valve destruction and abdominal aortic constriction). The
      cardiac function was detected by echocardiographic and hemodynamic assays. The
      mRNA expression levels of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) and
      phospholamban (PLB) were evaluated by RT-PCR. The protein expression levels of
      SERCA2a, PLB, phosphoserine 16-PLB (pSer-16-PLB) and protein kinase A (PKA) were
      evaluated by Western blot, and the phosphorylation status of PLB was determined
      by the ratio of pSer-16-PLB protein level to that of PLB. The activity of SERCA2a
      was measured through inorganic phosphate. The activity of PKA was measured by
      gamma-(32)P ATP-binding assays. Compared with SO group, there were significantly
      increased ventricular wall thickness, raised left ventricular end diastolic
      pressure (LVEDP), reduced diastolic function in DHF group (P<0.05 or P<0.01), and
      significantly increased ventricular cavity size and LVEDP, reduced systolic
      function in SHF group (P<0.05 or P<0.01). The expression levels of SERCA2a in DHF
      and SHF groups were lower than that in SO group (P<0.05), while the expression
      and activity of PKA in DHF and SHF groups were higher than that in SO group
      (P<0.05 or P<0.01), and there was no significant difference between DHF and SHF
      groups. The expression levels of PLB and pSer-16-PLB as well as the
      phosphorylation status of PLB and activity of SERCA2a in SHF group were lower
      than those in DHF and SO groups respectively. Posing a contrast, the
      phosphorylation status of PLB and activity of SERCA2a in DHF group were higher
      than that in SO group (P<0.05). These results indicate that the SHF and DHF
      models were successfully established, and there are some differences in the
      expression and activity of calcium regulatory proteins between two models.

PMID- 20029690
TI  - [High-frequency rotation sensation function damage of the crista of the
      horizontal semicircular canal induced by gentamicin and its morphological
      basis.].
AB  - The goal of the present study was to explore high-frequency rotation sensation
      function damage of the crista of the horizontal semicircular canal induced by
      gentamicin and its morphological basis. The guinea pigs were randomly divided
      into four groups (group 1, 2, 3 and control group, n=20). The animals of treated
      groups received gentamicin subcutaneously (50 mg/kg per day) for 1 week (group
      1), 2 weeks (group 2) and 3 weeks (group 3), respectively. The animals of control
      group were administered with equal volume of saline subcutaneously.
      Videonystagmography (VNG) evoked by ice water or high-frequency rotations, and
      vestibular evoked potential (VsEP) evoked by low- and high-frequency rotations
      were recorded after the administration. After VNG and VsEP were examined, the
      cristae of the horizontal semicircular canals were prepared for scanning and
      transmission electron microscopy. The results are as follows: (1) In VNG
      examination, after ice water stimulation, no obvious nystagmus was observed in
      the animals of group 3, and there was no significant difference in nystagmus
      frequency and duration among group 1, 2 and control group (P>0.05). After high-
      frequency rotations, no obvious nystagmus was yet observed in the animals of
      group 3. There were significant differences in the nystagmus frequency and
      duration of the VNG waves between the experimental group 2 and control group
      (P<0.01), and no difference was found between group 1 and control group (P>0.05).
      (2) In VsEP examination, there was no significant difference in the parameters of
      VsEP among group 1, 2 and control group (P>0.05), and VsEP was not observed in
      group 3 after low-frequency rotations. After high- frequency rotations, compared
      with control group, the latencies and amplitudes of P1 and P2 in group 2
      significantly decreased (P<0.01), while no changes were found in group 1
      (P>0.05). Group 3 had no response of VsEP to high-frequency rotations. (3)
      Electron microscopy was used to observe the crista hair cells of the four groups.
      In control group, the hair cells were normal. In group 1, almost normal
      appearance with slight edema of the hair cells was shown. In group 2, some hair
      cells in the central top of the crista necrosed, but other hair cells in the
      peripheral area showed normal appearance. In group 3, vestibular hair cells were
      entirely impaired or necrosis. These results show gentamicin selectively induces
      high-frequency rotation sensation function damage of the crista of the horizontal
      semicircular canal. The damage is concentrated on the central top area and then
      subsequently extended to the peripheral area of vestibular crista. It can be
      inferred that the hair cells in the central top area of the crista are involved
      in high-frequency rotation vestibular perception.

PMID- 20029691
TI  - Effect of quercetin on colon contractility and L-type Ca(2+) channels in colon
      smooth muscle of guinea-pig.
AB  - The aim of the present study was to investigate the effects of quercetin on colon
      contractility and voltage-dependent Ca(2+) channels in the single smooth muscle
      cell isolated from the proximal colon of guinea-pig and to clarify whether its
      effect on L-type Ca(2+) current (I(Ca,L)) would be related to its myorelaxing
      properties. Colon smooth muscle strips were used to take contractile tension
      recordings. Smooth muscle cells were freshly isolated from the proximal colon of
      guinea-pig by means of papain treatment. I(Ba,L) (barium instead of calcium as
      current carrier) was measured by using whole-cell patch-clamp techniques. The
      results showed that quercetin relaxed colon muscle strips in a concentration
      dependent manner and antagonized the contractile effect of acetylcholine and
      neostigmine. Preincubation with indomethcin [cyclooxygenase (COX) inhibitor] and
      methylene blue [guanylate cyclase (GC) inhibitor] significantly attenuated the
      relaxing effect of quercetin, respectively. Quercetin increased I(Ba,L) in a
      concentration- [EC(50)= (7.59+/-0.38) mumol/L] and voltage-dependent pattern, and
      shifted the maximum of the current-voltage curve by 10 mV in the depolarizing
      direction without modifying the threshold potential for Ca(2+) influx. Quercetin
      shifted the steady-state inactivation curve toward more positive potentials by
      approximately 3.75 mV without affecting the slope of activation and inactivation
      curve. H-89 (PKA inhibitor) abolished quercetin-induced I(Ba,L) increase, while
      cAMP enhanced the quercetin-induced I(Ba,L) increase. The patch-clamp results
      proved that quercetin increased I(Ba,L) via PKA pathway. It is therefore
      suggested that the relaxing effect of quercetin attributes to the interaction of
      GC and COX stimulation, as well as the antagonism effect on acetylcholine, which
      hierarchically prevails over the increase in the Ca(2+) influx to be expected
      from I(Ca,L) stimulation.

PMID- 20029692
TI  - [Intracellular recordings and multi-parameter analysis of long-term potentiation
      of synaptic responses in chick brain slices.].
AB  - Day-old chick is unique animal model in brain development and behavior study. The
      intermediate medial mesopallium (IMM), a region of the chick forebrain, is
      intimately involved in the early learning processes, which offers the ideal
      opportunity to study the neural changes that underlie behavioral plasticity. In
      this paper, the intracellular recordings were conducted from IMM neurons in chick
      forebrain slices, in which electrophysiological properties, synaptic responses
      and long-term potentiation (LTP) were observed. Coronal sections of left
      forebrains (500 mum thick), containing IMM, were prepared from domestic chicks,
      aged 2-10 days. In 69 IMM neurons, the resting membrane potential was measured to
      be (-59.4+/-5.3) mV, slope membrane resistance (70.8+/-27.2) MOmega, and time
      constant (10.2+/-4.3) ms. The amplitude, threshold, overshoot, half-width, max
      rise slope and max decay slope of action potential evoked by intracellular
      current injection were (85.2+/-9.4) mV, (-38.7+/-7.6) mV, (25.6+/-8.9) mV, (2.1+/
      0.5) ms, (150.5+/-41.2) mV/ms and (-64.3+/-14.0) mV/ms, respectively. Spike
      firing frequency was increased with depolarizing current intensity in 32 of 69
      tested cells [linear regression slope was (21.5+/-10.9) Hz/nA, P<0.05 in all
      cells]. The depolarizing synaptic responses (i.e. EPSPs), with stimulus intensity
      and membrane potential-dependent properties, were elicited by dorsal (n=25) or
      ventral (n=62) focal electrical stimuli at 0.1 Hz in all tested IMM neurons and
      could be nullified reversibly by perfusion with 100 mumol/L AP5 (NMDA receptor
      antagonist) and 3 mumol/L DNQX (non-NMDA receptor antagonist), but enlarged by 6
      mumol/L bicuculline (GABA(A) receptor antagonist). The EPSPs evoked by ventral
      stimulation were persistently increased after tetanic stimulation (5 Hz, 300
      pulses/train, 2 trains, train interval 10 min) in 6 of 12 tested IMM neurons. The
      amplitude of EPSPs was potentiated to more than 120% of control level (when
      analyzed at 45 min of enhancement, P<0.05, n=5), which lasted at least 30 min and
      then could be referred to as LTP. Moreover, area under curve, duration and max
      rise slope of EPSPs were also enhanced (P<0.05), while no significant changes
      were observed in the electrophysiological parameters of IMM neurons following
      induction of LTP (P>0.05). These results suggest that the intracellular recording
      techniques in the chick brain slices can be used to perform multi-parameter
      analysis of synaptic responses and their LTP.

PMID- 20029694
TI  - Psychometric support for an abbreviated version of the Behavior Rating Inventory
      of Executive Function (BRIEF) Parent Form.
AB  - The objectives of this study were to systematically develop and evaluate the
      psychometric properties of an abbreviated version of the Behavior Rating
      Inventory of Executive Function (BRIEF) Parent Report; a questionnaire widely
      used by pediatric neuropsychologists. A total of 24 items from the original BRIEF
      Parent Form were selected for the short-form, which was then evaluated in three
      complementary samples, according to six a priori psychometric criteria. The short
      form generally demonstrated appropriate psychometric qualities, with convincing
      evidence for the reliability and validity of the three composite indices:
      Behavioral Regulation, Metacognition, and the Global Executive Composite.
      Potential clinical applications include screening at-risk children in medical
      clinics to facilitate appropriate referrals for further psychological
      consultation. In research settings, the short-form can be easily integrated into
      studies involving mass collection of data (e.g., large-scale epidemiological
      research), facilitating advancements in the scientific understanding of
      neuropsychological morbidity in medically involved populations.

PMID- 20029693
TI  - A novel insight into neuroprotection against hypoxic/ischemic stress.
AB  - The use of opioid analgesics has a long history in clinical settings, although
      the functions of opioid receptors, especially their role in the brain, are not
      well understood yet. Recent studies have generated abundant new data on opioid
      receptor-mediated functions and the underlying mechanisms. The most exciting
      finding in the past decade is probably the neuroprotection against
      hypoxic/ischemic stress mediated by delta-opioid receptors (DOR). An up
      regulation of DOR expression and the release of endogenous opioids may increase
      neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending
      on stress duration and severity, different mechanisms at multiple levels to
      preserve neuronal survival, including the stabilization of ionic homeostasis, an
      increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti
      oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new
      concept of neuroprotection against neurological disorders and have a potentially
      significant impact on the prevention and treatment of some serious neurological
      conditions, such as stroke.

PMID- 20029695
TI  - Mental time in amnesia: evidence from bilateral medial temporal damage before and
      after recovery.
AB  - The human mind is continuously involved in "projecting" the self in time in order
      to process past memories and predict future occurrences. "Self-projection" in
      time involves episodic and spatial memory, relying on medial-temporal structures,
      but also engages visuo-spatial imagery, relying on occipito-temporal structures,
      and self-location, relying on temporo-parietal structures. Here we had the rare
      opportunity to investigate the relation between self-projection in time and
      memory, using a novel behavioural paradigm, in a patient with subacute bilateral
      medial-temporal damage during a period of amnesia as well as after recovery.
      Despite her memory deficit the patient was able to "project" herself to past and
      future, yet with significant improvement after recovery. We discuss our findings
      with respect to the relations between episodic memory and medial-temporal
      structures with self-projection in time to past and future.

PMID- 20029697
TI  - Profiles of emotional and behavioral sequelae following acquired brain injury:
      cluster analysis of the Personality Assessment Inventory.
AB  - Due to the multidimensional nature of symptom complaints within the acquired
      brain injury (ABI) population, emotional and behavioral profiles obtained from
      using comprehensive validated measures often yield more relevant information than
      tools that assess for symptoms of a single diagnostic disorder. The current study
      used the Personality Assessment Inventory (PAI) to detect emotional and
      behavioral profiles in a sample of 440 adult ABI patients. Using a rigorous three
      step cluster analytic approach, seven clusters were identified, indicating that
      half of the sample (50%) showed clinically significant affective and behavioral
      symptoms typified by multiple Diagnostic and Statistical Manual of Mental
      Disorders (DSM) Axis I and/or II features. Two of the subtypes showed severe and
      diverse affective symptoms but were distinguished from each other by antisocial
      features and substance use. Two other subtypes, with predominantly internalized
      presentations, were characterized by mainly depressive and somatic features, and
      the second by mild anxiety and cognitive disturbance. One group, predominantly
      externalized presentation, showed high substance use and antisocial features. The
      other part of the sample (50%) had no significant affective or behavioral
      complaints but were characterized by two profile types classified as essentially
      normal, but distinguishable by one having an increased tendency to minimize
      symptoms. Sex, age, marital status, education/preinjury, and vocation typified
      various subtypes. The identified profiles taken in the context of important
      demographic information can provide descriptive insight into the nature of
      postinjury affective and behavioral symptoms, facilitating more comprehensive
      conceptualization of the client's needs that can be addressed through more
      tailored interventions.

PMID- 20029698
TI  - Introducing the policy forum.

PMID- 20029699
TI  - Analysis and advocacy in home- and community-based care: an approach in three
      parts.
AB  - A new chapter in health policy presents both challenges and opportunities for
      aging policy analysts and advocates concerned with long-term care. Millions of
      long-term care recipients and providers live today in a pubic policy netherworld,
      one principally associated with Medicaid. I suggest here that moving policy
      forward will entail three key steps: (a) to overcome structural lag in key home
      and community-based care (HCBC) policy arenas; (b) to reverse a contemporary
      pattern of risk-shifting from institutions to individuals; and (c) to inform and
      empower caregivers to have their own pressing needs recognized. Recent
      developments in Washington provide new optimism on these fronts. Voluntary long
      term care and community-based care (LTC/HCBC) proposals are on the table within
      the broad context of health care reform. Whether they remain will be, in large,
      part a function of how far we have moved along the fronts described: modernizing
      policies, recognizing risks, and activating neglected policy constituencies.

PMID- 20029700
TI  - NORC supportive services model implementation and community capacity.
AB  - As community residents age, service delivery systems may not be equipped to meet
      their changing needs. The Naturally Occurring Retirement Community (NORC) model
      has emerged as a strategy to utilize existing resources and develop a
      comprehensive approach to maintaining older adult functional status. However,
      little has been written about how community capacity influences NORC
      implementation. A community capacity framework was used to analyze the themes
      that emerged from participant and service provider interviews at two diverse NORC
      sites. The findings revealed that perceptions of a sense of community and
      partnership management influenced the NORC experience for participants and
      providers.

PMID- 20029701
TI  - Long-term care in the United States: policy themes and promising practices.
AB  - This analysis provides an overview of the major policy themes and promising
      practices emerging in recent years as policymakers and researchers struggle to
      design a long-term care system that meets the needs of an aging population.
      Themes that have dominated the long-term care policy debates include: recruiting
      and retaining a qualified long-term care workforce; devising financing mechanisms
      for those requiring long-term care; and moving away from an institutional-based
      long-term care system towards more home- and community-based services. Three
      promising practices that have emerged in the past few decades include: the
      culture change movement; service integration that combines medical and social
      care; and various forms of community residential care that bring together housing
      and services in a more home-like environment. It concludes with long-term care
      recommendations for policymakers.

PMID- 20029702
TI  - The omission of comprehensive care: an analysis of the Nursing Home Reform Act of
      1987.
AB  - With the large increase in the older adult population, the number of people in
      need of nursing home services is expected to grow rapidly. The challenge is to
      attain or maintain the highest possible physical, mental and psychological well
      being of residents through provision of medically-related social services as
      required by the Nursing Home Reform Act (NHRA) of 1987. However, the basis of
      psycho-social service provision in NHRA is the size of the nursing home, which is
      questionable and is therefore making legislation less equitable. This policy
      analysis of NHRA will include suggestions of feasible policy alternatives to make
      the current legislation more equitable and effective. The article recognizes and
      endorses the contribution of social workers in psycho-social service provision
      and advocates for an increase in the ratio of mental health professionals to
      residents, therefore meeting the psycho-social service needs of the residents.

PMID- 20029703
TI  - Linking the NIH strategic plan to the research agenda for social workers in
      health and aging.
AB  - Although social work has a long and distinctive tradition of practice-relevant
      research aimed at enhancing the health and well-being of older adults, the
      profession has been underrepresented among the ranks of academic researchers and
      the National Institutes of Health's (NIH) scientific endeavors. In this article,
      the inherent capacities of social workers to generate and disseminate empirical
      health-related knowledge are discussed and recent developments in social work's
      geriatric research infrastructure are described. Emerging domains for advancing
      the profession's contribution to practice-relevant geriatric research on the
      federal level are identified and the next steps toward advancing the field's
      research agenda are posed.

PMID- 20029704
TI  - Learning from recruitment challenges: barriers to diagnosis, treatment, and
      research participation for Latinos with symptoms of Alzheimer's disease.
AB  - This article discusses barriers to diagnosis and treatment of Alzheimer's disease
      (AD) and concomitantly to participation in AD research as elicited from 29
      potential Latino participants who ultimately did not enroll in a study evaluating
      a caregiver intervention. Nearly half of all individuals contacting the
      researcher about the intervention study failed to meet criteria stipulating an
      existing AD diagnosis. Barriers to obtaining a diagnosis include lack of
      knowledge about AD, perceptions of memory loss as normal aging, and structural
      barriers to accessing care. A quarter of caregivers contacting the researcher
      felt too overwhelmed to participate. Many of these barriers have been previously
      identified as challenges to treatment, suggesting this is not just a
      methodological research problem, but inextricably tied to larger issues of AD
      knowledge and service accessibility. Engaging Latino communities equitably in the
      assessment of needs and the process of addressing them, thus ensuring the
      validity and applicability of the research and findings, is important both for
      increasing this group's participation in relevant studies and for addressing
      existing health disparities.

PMID- 20029706
TI  - Health care: America stands alone.

PMID- 20029707
TI  - Validating measures of scanned information exposure in the context of cancer
      prevention and screening behaviors.
AB  - Individuals may obtain health information, particularly from the mass media,
      without engaging in purposeful information searches (called scanning). This study
      used the Seeking and Scanning Behavior Survey of the General Population (SSBG), a
      nationally representative survey of adults aged 40-70 years (n = 2,489), to
      validate measures of scanned information exposure about cancer prevention and
      screening behaviors. Scanned exposure measures concerning specific behaviors
      (exercise; fruit and vegetable consumption; dieting; and mammogram, prostate
      specific antigen (PSA) text, and colonoscopy screening) have good face validity
      and are convergent across behaviors (mean correlation across six preventive
      behaviors = 0.50, sd = 0.09). These measures can be discriminated from measures
      of general media exposure (mean r = 0.23, sd = 0.02) and seeking exposure for the
      same behaviors (mean r = 0.25, sd = 0.06). Scanned information exposure was
      associated with weekly volume of newspaper coverage for two of six behaviors,
      providing additional evidence of nomological validity. Scanned information
      exposure at the first round of measurement was associated with identical exposure
      1 year later (mean r = .41, sd = .04). Scanned exposure measures also were
      significantly associated with five of the six preventive behaviors. These results
      provide evidence that scanned information exposure measures are valid indicators
      of the construct. Researchers might consider their use to capture scanned media
      influence on cognitions and behaviors.

PMID- 20029708
TI  - Disaster communication on the internet: a focus on mobilizing information.
AB  - While local television news is the most cited source for seeking news and
      information, many individuals also report finding their news from the Internet.
      During a disaster, people need access to accurate information and clear, specific
      instructions to help them act appropriately. Therefore, it is important to assess
      the volume and scope of emergency information being disseminated on local
      television news websites. This study analyzed the content of 293 emergency
      related stories on 119 local television news websites. Mobilizing information
      (MI), information found in news that can cue people to act on preexisting
      attitudes, also was explored. Results showed that emergency information was
      present on nearly all (96%) of the sites examined. A majority of news stories
      focused on natural disasters (52%) and most frequently discussed multiple
      disasters (e.g., hurricanes and pandemics). Mobilizing information was present in
      fewer than half of the stories (44%); stories were more likely to contain
      identificational MI than either locational or tactical MI (p < .05). There were
      also significant differences in type of MI present according to U.S. region. More
      stories by wire and syndicated services included MI (p < 0.05). Implications for
      future research on inclusion of MI in general health and emergency stories are
      discussed.

PMID- 20029709
TI  - Tobacco, alcohol, and other risk behaviors in film: how well do MPAA ratings
      distinguish content?
AB  - To evaluate the usefulness of Motion Picture Association of America (MPAA)
      ratings for parental selection of appropriate films for children, the 100 top
      grossing movies each year from 1996 through 2004 (N = 900) were content analyzed
      to measure risk behaviors in each film. More restrictive MPAA ratings (R and PG
      13) were associated with increased mean seconds of portrayals of tobacco use,
      alcohol use, and sexual content; increased frequency of violent content; and
      increased salience of drug use. MPAA ratings, however, did not clearly
      distinguish films based on tobacco or alcohol use. Fifty percent of R-rated
      movies contained 124 seconds or more of tobacco use, comparable with 26% of PG-13
      and 17% of PG movies. Fifty percent of R-rated movies contained 162 seconds or
      more of alcohol use, comparable with 49% of PG-13 and 25% of PG movies. Because
      of the high degree of overlap in alcohol and tobacco content between rating
      categories, the MPAA rating system, as currently defined, is not adequate for
      parents who wish to limit their children's exposure to tobacco or alcohol content
      in movies.

PMID- 20029711
TI  - Cancer prevention information seeking: a signal detection analysis of data from
      the cancer information service.
AB  - Communication and health information seeking play a significant role in the
      promotion of cancer prevention behaviors, including screening. Data from a sample
      of information seekers who contacted the National Cancer Institute's (NCI's)
      Cancer Information Service (CIS; N = 20,412) were split randomly into an
      exploratory and validation sample to conduct signal detection analysis predicting
      cancer prevention information seeking. Important predictors of seeking prevention
      information in the exploratory sample were type of information seeker,
      communication channel, age, and gender; these findings generally were confirmed
      in the validation sample. Our findings also reveal important information about
      the demographic characteristics and communication channel preferences of cancer
      prevention information seekers.

PMID- 20029710
TI  - Disclosing the disclosure: factors associated with communicating the results of
      genetic susceptibility testing for Alzheimer's disease.
AB  - This study explored the extent to which recipients of genetic susceptibility
      testing for Alzheimer's disease (AD) communicated their results to others. It
      also examined demographic characteristics, along with beliefs about AD,
      associated with such communication. Participants (N = 271) in a randomized
      clinical trial involving genetic testing for Apolipoprotein E (APOE) gene
      variants among first-degree relatives of AD patients reported their communication
      behaviors 6 weeks after the results disclosure. Information on beliefs about AD
      and genetic testing was collected at baseline. Eighty-two percent of participants
      receiving APOE genotype information shared their results with someone.
      Specifically, 64% shared with family members, 51% with spouse or significant
      others, 35% with friends, and 12% with health care professionals. Greater AD
      treatment optimism was associated with communicating results to family (OR =
      1.43), spouse (OR = 1.62), friends (OR = 1.81), and health care professionals (OR
      = 2.20). Lower perceived risk (OR = 0.98) and higher perceived importance of
      genetics in the development of AD (OR = 1.93) were associated with results
      communication in general. Lower perceived drawbacks of AD genetic testing was
      associated with results communication to friends (OR = 0.65). Beliefs about AD
      risks and causes, genetic testing, and development of treatments partly may
      determine the interpersonal communication patterns of genetic susceptibility test
      results.

PMID- 20029712
TI  - What can I learn from this interaction? A qualitative analysis of medical student
      self-reflection and learning in a standardized patient exercise about disability.
AB  - Patients with disabilities receive fewer health services than the general
      population, yet they have greater health needs. Similarly, physicians report
      limited training in disability. The current project examines medical students'
      learning about disability in a project using individuals with disabilities as
      medical educators. Family medicine clerkship students (N = 138) across an
      academic year were videotaped during interviews with standardized patient
      educators with disabilities and during feedback sessions following the
      interactions. Qualitative analysis of feedback transcripts identifies three
      primary areas of integrating learning, reflective practice, and disability: (1)
      learning how disability impacts the treatment plan, (2) self-reflection and
      recognizing attitudes about disability, and (3) learning about the practice of
      medicine generally from the disability exercise. Themes are identified within
      each of the primary learning areas. Medical student reflection provides evidence
      of learning to connect disability with pain, everyday life, and treatment.
      Medical students learned to recognize patients' expertise in their own condition
      and in health care navigation. Medical students also examined how their language
      implies attitude. The current investigation provided evidence of the ways
      examining disability can serve as a cornerstone for building relationship
      centered patient care and encouraging reflective practice overall.

PMID- 20029714
TI  - Underestimation of terpene exposure in the Nordic wood industry.
AB  - This study determined that emission of sesquiterpenes from processed wood
      warrants attention in the work environment. Currently, only the monoterpenes in
      the terpene group are monitored in occupational hygiene studies. Terpene
      emissions are a work environment issue for industries that process wood, as they
      are known to cause respiratory difficulties and mucous membrane irritation. Fresh
      sawdust of the most common boreal conifers, Norway spruce (Picea abies) and Scots
      pine (Pinus sylvestris), was subjected to processing (drying), and the emissions
      were analyzed with a gas chromatograph-mass spectrometer. The data indicate that
      workers are exposed to significant amounts of sesquiterpenes, an observation that
      has not been recorded previously at wood processing plants. On average, the
      proportion of sesquiterpenes to monoterpenes was 21 +/- 5% (STD, n = 11) for
      spruce and 15 +/- 5% (STD, n = 13) for pine. The composition of terpenes emitted
      in air from spruce wood differs from the composition in resin. The sum of
      monoterpenes and sesquiterpenes can exceed the occupational exposure limit for
      turpentine for processes where monoterpene concentrations are already close to
      the occupational exposure limit, and for processes involving the processing of
      bark. Findings suggest that future studies of health effects from terpenes in air
      should measure monoterpenes and sesquiterpenes to assess whether the current OELs
      are appropriate.

PMID- 20029715
TI  - Efficacy of a cognitive training programme for mild cognitive impairment: results
      of a randomised controlled study.
AB  - This study aimed to determine the efficacy of cognitive training in a 10-week
      randomised controlled study involving 22 individuals presenting with mild
      cognitive impairment of the amnestic type (MCI-A). Participants in the
      experimental group (n = 11) learned face-name associations using a paradigm
      combining errorless (EL) learning and spaced retrieval (SR) whereas participants
      in the control group (n = 11) were trained using an errorful (EF) learning
      paradigm. Psycho-educational sessions on memory were also provided to all
      participants. After neuropsychological screening and baseline evaluations, the
      cognitive training took place in 6 sessions over a 3-week period. The post
      training and follow-up evaluations, at one and four weeks respectively, were
      performed by research assistants blind to the participant's study group. The
      results showed that regardless of the training condition, all participants
      improved their capacity to learn face-name associations. A significant
      amelioration was also observed in participant satisfaction regarding their memory
      functioning and in the frequency with which the participants used strategies to
      support memory functions in daily life. The absence of difference between groups
      on all variables might be partly explained by the high variability of scores
      within the experimental group. Other studies are needed in order to verify the
      efficacy of EL learning and SR over EF in MCI-A.

PMID- 20029717
TI  - President's Annual State of the Academy Report.

PMID- 20029718
TI  - Bowden, shores, & Mathias (2006): failure to replicate or just failure to notice.
      Does effort still account for more variance in neuropsychological test scores
      than TBI severity?
AB  - Several studies have reported that traumatic brain injury (TBI) has a smaller
      effect on neuropsychological test scores, in contrast to the large effect of poor
      effort on test performance. Consequently, many authors have concluded that effort
      needs to be measured routinely and that it is necessary to control for poor
      effort when measuring the effects of brain disease or injury on performance.
      Recently, however, Bowden, Shores, and Mathias (2006) have challenged these
      notions. They argued that the Immediate Recognition subtest of the Word Memory
      Test (Green & Flaro, 2003), an effort measure, is another verbal memory test
      rather than a measure of cognitive effort. In this study we re-examine the data
      from Bowden et al. (2006) and Green, Rohling, Lees-Haley, and Allen (2001) to
      identify differences between the two studies that might account for their
      contradictory conclusions. In both sets of data, reanalysis showed that effort
      explains approximately five times more of the variance in composite
      neuropsychological test scores than TBI severity. Importantly, scores on the Word
      Memory Test-Immediate Recognition (WMT-IR) were not correlated with measures of
      TBI severity, and were not found to correlate with major variables known to be
      measuring ability (e.g., years of education). These findings challenge the
      conclusions offered by Bowden and colleagues (2006).

PMID- 20029719
TI  - [Abstracts of a research workshop pulmonary hypertension].

PMID- 20029734
TI  - Walking economy of adults with Down syndrome.
AB  - This study intended to investigate walking economy (WE) in response to different
      treadmill speeds and grades in adults with Down syndrome (DS) and in non-disabled
      controls. Eighteen participants (14 males; 4 females) with DS (33.6+/-7.6 years)
      and 16 non-disabled (12 males, 4 females) controls (33.3+/-8.0 years) performed
      submaximal (2.5 km . h (-1) and 4 km . h (-1) at 0% grade; 4 km . h (-1) at 2.5%
      and 5% grade, for 5 min each) and maximal treadmill tests with metabolic and
      heart rate measurements. Oxygen uptake (VO(2)) was not different between groups
      at rest or during the slowest treadmill speed. However, at faster speeds and
      increased grades, adults with DS presented lower WE than controls (p<0.0001).
      Subsequent analyses revealed that, despite showing higher delta VO(2) response to
      the selected speed increments (p<0.0001), individuals with DS produced similar
      VO(2) increase as controls to grade variations. Therefore, adults with DS exhibit
      lower WE than non-disabled controls at a speed faster than their preferred
      walking speed. Additionally, in comparison to controls, individuals with DS show
      a greater change in energy expenditure with a change in walking speed. In
      conclusion, lower WE in individuals with DS is mainly related to their inability
      to adapt efficiently to positive variations in walking speed.

PMID- 20029735
TI  - Kinematical profiling of the front crawl start.
AB  - This study analysed the start phases of 15 elite front crawl swimmers, all
      specialists of sprint events. The first aim was to determine which phases were
      correlated with the 15-m start time. The features common to the sample of
      swimmers were then established and individual profiles were clustered. The
      subjects performed two 25-m trials at the 50-m race-pace using their preferential
      start technique (grab start). The kinematical analysis assessed the durations of
      the block, flight, entry, glide, leg kicking and full swimming phases to the 15-m
      mark. Stroking parameters and the index of arm coordination (IdC) were analysed
      for the swimming part (10-20 m) of the 25-m. Through the swimming part IdC
      increased while stroke length and velocity decreased (p<0.05). The relative
      durations of the aerial (block, flight), entry and underwater phases were
      correlated with start time. Inter-subject variability was observed, which
      suggests that various motor solutions were used for the start. Notably, four
      clusters led to a short 15-m start time: the leg kicking style, mixed "leg
      kicking/swimming" style, long glide style and short glide style.

PMID- 20029736
TI  - Performance trends in 161-km ultramarathons.
AB  - This report documents performance-related trends in 100-mile (161-km)
      ultramarathon running competitions in North America. A retrospective analysis of
      results from 1977 through 2008 revealed that annual finish rates increased
      initially and then plateaued by the early 1990s at nearly 60%. The fastest times
      were produced by the 30-39 year age group among the men and the 40-49 year age
      group for the women. Finish times of women improved relative to men through the
      1980s, but were then stable over the past two decades with the fastest women
      running about 20% slower than the fastest men. Additionally, the average times of
      the fastest runners did not change over the past two decades for any age group
      for either sex. The percentage difference in finish times between the first and
      fifth place runners has remained lower (p<0.0001) for men than women, and has
      shown an upward trend (p=0.003) across time for men. It is concluded that
      increasing participation in 161-km ultramarathons in North America has not been
      associated with improvements in performance or depth of competition with the
      exception of the relative improvements in finish times for women compared with
      men that was evident through the 1980s.

PMID- 20029737
TI  - Equal BMD after daily or triweekly exercise in growing rats.
AB  - The purpose of this study was to examine the efficacy of continuous resistance
      training (3 days/wk) compared to interrupted resistance training where 20-24 h
      separated an exercise bout (i. e. 6 days/wk) for enhancing bone mineral density
      (BMD) in growing male rats. The total volume of work performed per week between
      the two resistance training programs was equivalent by design. Young male rats
      were randomly divided into Control (Con, n=9), 3 days/wk resistance trained group
      (RT3, n=9), and 6 days/wk resistance trained group (RT6, n=9). The RT3 and RT6
      groups were conditioned to climb a vertical ladder with weights appended to their
      tail for a total of 6 wks. After 6 wks, BMD (assessed via DXA) from the left
      tibia was significantly greater for RT3 (0.242+/-0.004 g/cm (2)) and RT6 (0.244+/
      0.004 g/cm (2)) compared to Con (0.226+/-0.003 g/cm (2)). Further, serum
      osteocalcin (oc, in ng/ml) was significantly greater for RT3 (75.8+/-4.4) and RT6
      (73.5+/-3.8) compared to Con (53.4+/-2.4). There was no significant difference in
      BMD or serum OC between RT3 and RT6 groups. The results indicate that both
      resistance training programs were equally effective in elevating bone mineral
      density in young, growing rats.

PMID- 20029738
TI  - In vivo assessment of both active and passive parts of the plantarflexors series
      elastic component stiffness using the alpha method: a reliability study.
AB  - The aim of this study was to investigate the reliability of an in vivo adaptation
      of the short range stiffness experiment associated with the application of a
      mathematical model to determine the stiffness of both torque dependent and
      independent components of the plantarflexors series elastic component. Fourteen
      subjects participated in this study. The experimental protocol consisted of
      quickly moving the ankle joint in dorsiflexion during constant voluntary
      isometric plantarflexion at 7 submaximal torque levels. Relationships between
      joint stiffness and torque were established and the stiffness of both torque
      dependent and independent components were determined using the alpha method. The
      day-to-day reliability was assessed for joint stiffness and stiffness of both
      torque dependent and independent components (ICC higher than 0.88 and CVs lower
      than 6.0%). This method could then be used to better understand adaptive
      subjacent mechanisms to assess the effects of training protocols, and the
      rehabilitation of neuromuscular pathologies or traumatisms.

PMID- 20029739
TI  - Echocardiography of the right ventricle in athlete's heart and hearts of normal
      size compared to magnetic resonance imaging: which measurements should be applied
      in athletes?
AB  - Right ventricular (RV) pathologic hypertrophy and cardiomyopathy have been
      reported to be related to ventricular arrhythmias and sudden cardiac death in
      athletes. However, it is unclear which echocardiographic measurements reflect RV
      dimensions in athlete's heart (AH) correctly. We aimed to compare two-dimensional
      echocardiography of the RV in AH and normal hearts to magnetic resonance imaging
      (MRI), and derive recommendations for RV echocardiography in athletes. Twenty
      three healthy male endurance athletes with AH (A; 28+/-4 yrs) and 26 healthy
      untrained males (C; 26+/-4 yrs) matched for body-dimensions were examined. In
      recommended echocardiographic parasternal and 4-chamber views, three enddiastolic
      RV free wall-thicknesses (T1,T5,T9) and RV diameters were determined (M-mode
      enddiastolic diameter [RV-EDD]; longitudinal [RV-LAX], sagittal, outflow-tract
      and tricuspid valve anulus diameters). MRI determined RV enddiastolic volumes (RV
      EDV) and masses (RVM) in A and C were: 162+/-29 vs. 136+/-15 ml and 76+/-10 vs.
      59+/-13 g (p<0.001). Significant correlations between RV-EDV and RV-EDD (r=0.49;
      p=0.001) as well as RV-LAX (r=0.38; p=0.01), and RVM and T5 (r=0.52; p=0.01) were
      found. For RV echocardiography, significant differences between A and C were
      documented for RV-EDD (medians [quartiles]: A: 26 mm [24/29 mm]; C: 22 mm [21/27
      mm]; p=0.04; measurable in 49/49 subjects), and in the parasternal short axis
      view for T5 (A: 6.0 mm [5.4/7.8 mm]; C: 5.0 mm [4.5/5.2 mm]; p=0.04; measurable
      in 22/49). In conclusion, two-dimensional echocardiographic RV measurements offer
      only a limited potential to reflect true RV dimensions. Only RV-EDD may
      differentiate between normal hearts and exercise related RV adaptations in AH,
      and is the only recommendable parameter to be measured in athletes routinely. In
      unclear cases additional methods should be used to examine the RV in athletes.

PMID- 20029740
TI  - ACE DD genotype is unfavorable to Korean short-term muscle power athletes.
AB  - The purpose of this study was to test the hypothesis that the ACE DD genotype is
      unfavorably associated with the ultimate power-oriented performance. To test the
      hypothesis we recruited a total of 848 subjects including 55 international level
      power-oriented athletes (High-performance), 100 national level power-oriented
      athletes (Mid-performance) and 693 healthy controls (Control) in Korea. Then the
      distributions of ACE polymorphism throughout these groups were analyzed. As a
      result, there was a gradual decrease of frequencies of the DD genotype with
      advancing levels of performance (Control vs. Mid-performance vs. High
      performance=17.2% vs. 10.0% vs. 5.5%, p=0.002). Also, the frequencies of D allele
      decreased gradually with advancing levels of performance (Control vs. Mid
      performance vs. High-performance=42.6% vs. 35.0% vs. 30.9%, p<0.01). Therefore,
      power-oriented athletes at the top level had a markedly diminished frequency of
      the DD genotype and the D allele. This finding gave 3.83 times lower probability
      of success in power-oriented sports for individuals with the DD genotype than
      those with the II+ ID genotype. In conclusion, these results indicate that Korean
      power-oriented athletes with a lower frequency of the DD genotype had a lower
      probability of success in power-oriented sports.

PMID- 20029741
TI  - [The thoracoscopic talc pleurodesis with intraoperative pleural biopsy - a
      retrospective analysis in patients with malignant pleural effusion].
AB  - BACKGROUND: The thoracoscopic pleurodesis with talc is an established therapy in
      case of malignant pleural effusion. With the instillation of talc a -localised
      inflammation is induced. However, some-times it turns into a severe systemic
      reaction. In this study of the postoperative course, the -question is examined
      whether a pleural biopsy is an additional risk factor for morbidity and mortality
      after talc pleurodesis. PATIENTS AND METHODS: Between January 2002 and December
      2004, 77 patients with a malignant pleural effusion were enrolled in this
      retrospective trial. All patients received a thoracoscopic talc pleurodesis. The
      patients were divided retrospectively into two groups: 50 patients with an intra
      operative pleural biopsy, 27 patients without a biopsy were the control group. C
      reactive protein (CrP), leukocytes, and creatinine were -analysed. RESULTS: In
      both groups, CrP and leukocytes increased postoperatively with a peak on day 2 or
      3. In general, the analysed data for creatinine -showed in the median standard
      values but with a high range up to at most 317 micromol / L on the 2 (nd)
      postoperative day, also in both groups. At no time was any significant difference
      in laboratory values seen among the two groups. Concerning morbidity and
      mortality also no significant difference could be determined. CONCLUSIONS: There
      were no significant differences for the examined laboratory values or for the
      morbidity / mortality between the two groups. That is why a disadvantage for
      patients with an intraoperative pleural biopsy is not to be expected.

PMID- 20029742
TI  - [Science and research in academic plastic surgery in Germany].
AB  - Plastic surgery has passed through a very positive evolution in the last decades
      on the solid fundament of constantly developing academic plastic surgery. Aim of
      this paper is an objective evaluation of the current status of academic plastic
      surgery regarding research topics, currently available ressources and scientific
      outcome based on a questionnaire. The return rate of the questionnaire in
      academic departments was 92%. Main topics in research besides wound healing were
      topics from regenerative medicine such as tissue engineering, biomaterials,
      genetherapy and angiogenesis with the main focus on skin and fat tissues. In the
      past five years a total of 25 million Euros of third party research grants were
      raised. Research relied mainly on interdisciplinary research facilities.
      Regarding the scientific outcome more than 200 scientific papers were published
      in basic science research journals having an impactfactor higher than two. These
      results clearly demonstrate that plastic surgery is scientifically highly
      productive in academic surroundings where independent departments are
      established. Considering that independent units of plastic surgery exist in a
      relatively small number of all 36 university hospitals in germany, it has to be
      claimed for further independent departments so to provide adequate research
      facilities for further evolution of academic plastic surgery.

PMID- 20029743
TI  - Students' perceptions of the effectiveness of a professional skills program in
      preparation for clerkship training.
AB  - CONTEXT: The goal of the Professional Skills Program at Arabian Gulf University,
      Bahrain, is to prepare medical students for the clerkship phase. In the six-year
      integrated problem-based learning (PBL) medical program, the Professional Skills
      Program is introduced in years two to four. The aim of this study was to evaluate
      program effectiveness as perceived by the students in the clerkship phase.
      METHOD: Students' perceptions were obtained using a mailed questionnaire. Close
      ended questions were assessed using a 5-point Likert scale. Students were also
      asked to comment on areas of strengths or suggestions for improvement. The
      questionnaire was piloted with a group of students in the clerkship years.
      Results were analyzed in relation to the different domains of the program.
      RESULTS: Students were positive about their clinical skills training in preparing
      them for their clerkship in relation to three levels of Kirkpatrick outcome
      measures. This was particularly true for the domains of physical examination and
      procedural skills. However, they indicated some areas in need of program
      development, particularly in the history-taking domain. CONCLUSION: The students'
      opinions generally support the effectiveness of the Professional Skills Program
      training in preparing them for the clerkship phase. Program evaluation has helped
      us to plan for further development of the program.

PMID- 20029744
TI  - The educational environment and self-perceived clinical competence of senior
      medical students in a Malaysian medical school.
AB  - INTRODUCTION: The educational environment is widely considered to be a major
      factor affecting students' motivation and learning outcomes. Although students'
      perceptions of their educational environment are often reported, we are unaware
      of any published reports that relate this information to students' clinical
      competence, either self-perceived or objectively measured. OBJECTIVES: We aimed
      to correlate students' perceptions of their learning environment and their self
      perceived competence in clinical, practical and personal skills, using validated
      scales. METHODS: Subjects included a cohort of 71 final-year medical students who
      were posted to a peripheral campus affiliated with a district hospital. Two
      questionnaires were administered concurrently: a modified DREEM (50 items) to
      assess the learning environment and an abbreviated IMU Student Competency Survey
      (29 items) to examine self-perceived competence across a wide range of skills and
      work-readiness. We correlated the major domains in both surveys using Spearman's
      Correlation. FINDINGS: Fifty-nine students (83%) completed the questionnaires.
      Comparing correlations of the five major domains of the modified DREEM
      questionnaire ("Perception of learning", "Perception of teachers", "Academic self
      perception", "Perception of atmosphere" and "Social self-perception") with all
      subscales in the abbreviated IMU Student Competency Survey (clinical, practical,
      personal skills and overall work-readiness), we found that academic self
      perception domain had the strongest correlations (r:0.405 to 0.579, p:0.002 to <
      0.001) and perception of teachers bears the weakest correlations (r:0.171 to
      0.284, p:0.254 to 0.031). Self-perceived competence in practical skills in the
      IMU Student Competency Survey correlated the weakest with all domains of the
      modified DREEM (r:0.206 to 0.405, p:0.124 to 0.002). DISCUSSION AND CONCLUSION:
      The overall weak-to-moderate correlations between perceptions of learning
      environment and self-perceived clinical competence suggest that other factors
      might interact with the learning environment to determine students' confidence
      and achievements.

PMID- 20029745
TI  - Barriers to advanced education for indigenous Australian health workers: an
      exploratory study.
AB  - INTRODUCTION: Aboriginal Health Workers (AHWs) play a crucial role in the
      delivery of primary health care services in underserved rural and remote
      communities throughout Australia. The Mount Isa Centre for Rural and Remote
      Health (MICRRH), in Northwest Queensland, Australia, has been involved in
      training AHWs since 2001. During this time, it has been observed that while there
      has been interest in pursuing further education in other health careers, the
      uptake for advanced study by AHWs has been minimal. This exploratory study was
      designed to assess the career aspirations of local AHWs (both qualified and
      students) as well as community stakeholder views to identify barriers experienced
      when undertaking advanced education. METHODS: The study used a descriptive and
      exploratory design. AHWs and key stakeholders were invited to participate. Open
      ended interviews were undertaken with nine participants in two communities in the
      Mount Isa Health Service District in Northwest Queensland, Australia. FINDINGS:
      While there was some interest expressed in careers like medicine and nursing, the
      majority of participants indicated a preference for advancement to management or
      specialist areas as AHWs. In relation to the barriers faced by AHWs and students
      in continuing study or career advancement, three main themes emerged: support;
      infrastructure; and promotion.

PMID- 20029746
TI  - Realising whanau ora through community action: the role of Maori community health
      workers.
AB  - CONTEXT: In New Zealand, the government's key strategy to improve the health of
      the indigenous population is advanced through a policy where families are
      supported to achieve their maximum health and well-being: "whanau ora" (for a
      glossary of Maori words and phrases, see appendix). OBJECTIVES: This paper
      outlines the role Maori community health workers (CHWs) play in the delivery of
      whanau ora services and explores the tensions and challenges faced by these
      workers in carrying out their role. METHODS: Recent literature, existing
      qualitative research data and local level verification from a practising
      community health worker with 12 years experience. FINDINGS: Roles were complex,
      varied and generally executed in high need communities. Differing expectations
      between the contractual requirements, the community and the CHW's own
      expectations meant CHWs continually managed competing demands. CHWs describe
      training opportunities as being short-term and ad hoc, specific to a particular
      health provider's needs and offering only limited options for career advancement.
      CONCLUSION: CHWs form an integral part of the New Zealand health workforce acting
      as the interface between the health sector and Maori communities. By working in a
      culturally distinctive manner, they help give effect to Maori health development
      aspirations. Increasingly this work is carried out in complex and demanding
      environments. Key challenges that need to be resolved to further advance the
      position of CHWs in New Zealand include greater recognition of the unique role
      they play in the delivery of public health and primary healthcare services,
      linking this recognition to appropriate remuneration and ensuring ongoing role
      development is met within a Maori worldview.

PMID- 20029747
TI  - Standardization of rotation schedules for pharmacy students' advanced practice
      rotations and potential impact on rotation site availability.
AB  - BACKGROUND: Increasing enrollment in pharmacy schools has led to a shortage of
      adequate advanced pharmacy practice experience (APPE) sites. OBJECTIVE: We sought
      to assess our preceptors' support for a standardized rotation schedule for the
      multiple schools that compete for APPE sites in our area. A secondary objective
      was to ascertain preceptors' beliefs about the impact a regional standardized
      rotation schedule might have on the number of students their sites would be able
      to accept on rotation. METHODS: A short questionnaire was developed. All APPE
      preceptors at our institution were invited to participate by e-mail, telephone
      and/or U.S. mail. RESULTS: A total of 232 preceptors were contacted;
      questionnaires were returned by 133 preceptors (57%). A proposed region-wide
      rotation schedule was supported by 75.2% of respondents. Most (79%) believed that
      the standardization of schedules will not affect the number of students they will
      be able to accommodate on rotations, while 18.1% believed the new schedule will
      allow them to accept more students. CONCLUSION: APPE preceptors in our area
      generally support standardization of pharmacy students' community rotation
      schedules, and this may increase the APPE availability but perhaps for only a
      minority of sites.

PMID- 20029749
TI  - Applied topics in the essentials of public health: a skills-based course in a
      public health certificate program developed to enhance the competency of working
      health professionals.
AB  - INTRODUCTION: In addition to understanding core public health fundamentals,
      health professionals must also be equipped with the skills necessary to implement
      strategies to promote population health. In response, the University of New
      Hampshire (UNH) has developed a unique Public Health Certificate (PHC) Program
      designed to strengthen knowledge and skills in basic public health competencies
      of working health professionals. A distinctive feature of this program is its
      culminating course "Applied Topics in the Essentials of Public Health," which
      entails a practical, applied learning experience where students explore a variety
      of essential public health services (EPHS) relevant to their career goals.
      OBJECTIVES: 1) Explain the rationale for educating working health professionals
      about public health; 2) Describe the UNH graduate PHC Program, its framework and
      innovative process for implementing a skills-based course to improve the
      competency of practitioners to perform the EPHS; 3) Review the benefits and
      challenges of implementing a skills-based course for working health
      professionals; and 4) Evaluate the PHC Program. DISCUSSION: The UNH PHC Program
      and its capstone course serve as a model for providing a unique, skills-based
      learning opportunity for working health professionals pursuing advanced public
      health education in U.S.-based or international public health education programs.
      This novel course design allows for students to develop the skills necessary to
      perform the EPHS.

PMID- 20029750
TI  - Blended E-learning in a Web-based virtual hospital: a useful tool for
      undergraduate education in urology.
AB  - INTRODUCTION: E-learning is a teaching tool used successfully in many medical
      subspecialties. Experience with its use in urology, however, is scarce. We
      present our teaching experience with the INMEDEA simulator to teach urological
      care to medical students. METHODS: The INMEDEA simulator is an interactive e
      learning system built around a virtual hospital which includes a department of
      urology. It allows students to solve virtual patient cases online. In this study,
      students were asked to prepare two urological cases prior to discussion of the
      cases in small groups. This blended teaching approach was evaluated by students
      through anonymous questionnaires. RESULTS: Of 70 4th year medical students 76%
      judged this teaching method as good or very good. Eighty-seven percent felt that
      it offered a good way to understand urological diseases better and 72% felt that
      learning with this method was fun. Nevertheless, 30 out of 70 free text
      statements revealed that further improvements of the program, including an easier
      and more comfortable navigation and a faster supply of information are necessary.
      CONCLUSIONS: Virtual patient cases offer a practicable solution for teaching
      based on problem solving in urology with a high acceptance rate by students.

PMID- 20029748
TI  - Clinical community health: revisiting "the community as patient".
AB  - INTRODUCTION: A little over fifty years ago, Edward McGavran, Dean of the
      University of North Carolina School of Public Health, articulated the concept of
      treating the community as if it were a patient. Although McGavran was addressing
      public health practitioners, the concept has applicability in academic medicine
      and reflects contemporary thought in patient care, research, and education. The
      goals of this paper are (1) to present a framework through which clinicians can
      conceptualize the community as an appropriate level of intervention to improve
      health, to conduct research and to educate students, and (2) to illustrate the
      framework by presenting information on how programs at Morehouse School of
      Medicine have used it to organize community-focused initiatives. The concept may
      be called Clinical Community Health. CLINICAL COMMUNITY HEALTH AND ITS
      APPLICATIONS AT MOREHOUSE SCHOOL OF MEDICINE: Health problems of communities are
      more readily understood by clinicians when analyzed in the same way that
      clinicians analyze the health problems of individual patients: by gathering
      subjective and objective data, formulating an assessment that is expressed as a
      problem list, and developing a plan ("SOAP"). The plan is created in consultation
      with the community, much as a modern physician engages in shared decision-making
      with a patient rather than issuing "doctor's orders." Similarly, community-based
      participatory research creates a relationship between the researcher and the
      community that parallels the relationship between the researcher and the
      individual research participant in traditional clinical research. When viewed
      through this lens, the education of students in the community resembles the
      education of students in the hospital or clinic--both are a type of service
      learning. Hence, the community work of faculty is best evaluated and rewarded in
      a fashion that parallels evaluation of faculty work in the clinic or hospital.
      This paper reports on our experiences at Morehouse School of Medicine (MSM), a
      historically black institution in the United States whose mission focuses on
      primary care and the health of the underserved. We report on our efforts to apply
      the model in service, research, and education. CONCLUSION: Viewing the community
      as a patient provides a useful conceptual framework for primary care physicians
      and other clinicians, since it allows them to recognize that it is not necessary
      to learn a different conceptual framework to diagnose and treat the community;
      rather, one can think of the community as a patient and apply a similar approach
      to that used in the care of individuals.

PMID- 20029751
TI  - Experiences of The Network: Towards Unity for Health Women and Health Taskforce.
AB  - CONTEXT: Women's health is an often neglected component of health professions
      education despite the well-documented need to improve the health status of women,
      especially in low income countries. This paper was written on behalf of all
      members of The Network: Towards Unity for Health Women and Health Taskforce
      (WHTF) which unites leaders in women's health and higher education from different
      countries around the world. The WHTF objectives include teaching health providers
      the skills and knowledge necessary to improve care to women; encouraging
      universities to partner with community women's groups; promoting the inclusion of
      women's rights and gender issues in curricula; and cultivating leadership among
      female health professions students. OBJECTIVE/CONTENT: The main goal of the paper
      is to provide an overview of the collaborative processes, the accomplishments and
      the lessons learned in this project since the early 1990s. It includes the
      history and evolution of the Taskforce; the importance of human rights and gender
      issues in approaching women's health; teaching tools--the Women and Health
      Learning Package (WHLP); implementation of WHLP in health professions education
      and community settings; and main outcomes and future challenges. The WHLP was
      implemented in fourteen universities and seven university community programs. A
      new edition of WHLP will be available in 2009. CONCLUSION: The WHTF is a model of
      south-south collaboration in health professions education and community programs
      to improve women's health. It has been successful in reaching universities and
      communities all over the globe and provides a model for other education, health
      and community issues.

PMID- 20029752
TI  - Realistic expectations: the changing role of paraprofessional health workers in
      First Nation communities in Canada.
AB  - CONTEXT: First Nation communities in Canada rely on a mix of non-indigenous
      professionals and large numbers of indigenous paraprofessionals to deliver
      healthcare. Formerly allowed to perform controlled acts in emergencies, the
      direct care role of paraprofessionals is now restricted because of concerns about
      liability and accountability. As such, they are limited to health promotion and
      prevention activities. OBJECTIVES: Focusing on the largest group of indigenous
      health workers, viz. Community Health Representatives (CHRs), for illustration
      purposes, this paper (1) examines the evolving role of First Nation health
      workers, and (2) discusses the proposed introduction of competency-based
      standards for their education, certification and regulation. METHODS: The paper
      is informed by findings from open ended, semi-structured and focus group
      interviews, as well as qualitative survey data, derived from seven studies done
      in Ontario, Canada. OUTCOMES: Paraprofessionals face conflicting and sometimes
      unrealistic expectations. Past practices have accustomed community members to
      hands-on care; however, professionals will no longer delegate tasks requiring
      clinical skills to them. Moreover, First Nation leaders are concerned about
      liability for their paraprofessional employees' actions. The paper discusses
      issues related to paraprofessional competence, preparation for practice, and
      continuing health education. It then presents the National Indian and Inuit
      Community Health Representatives Organization's proposal to establish a scope of
      practice and set of competencies that can form the basis for national practice
      and training standards, accreditation and regulation. CONCLUSIONS: In Canada or
      elsewhere, changing practice environments may require adjustments in the roles
      played by indigenous health workers. The case of First Nation Community Health
      Representatives illustrates a strategy for role transformation.

PMID- 20029753
TI  - Developing a tool for measuring quality of medical education.

PMID- 20029755
TI  - In the News! An opinion. "Wat kan ik voor u doen?" towards culturally competent
      communication.

PMID- 20029754
TI  - Scientific publication productivity of Libyan medical schools: a bibliometric
      study of papers listed in PubMed, 1988-2007.
AB  - BACKGROUND: Scientific publication is a vital mission of medical schools and it
      is important to periodically document how well schools fulfil this mission. AIMS:
      This study aimed to analyse the publication record of Libyan medical schools in
      international journals indexed in PubMed between 1988 and 2007. METHODS: Medline
      was searched using PubMed for publications affiliated to Libya during 1988-2007.
      RESULTS: Out of 417 papers related to Libya, 348 (84%) are affiliated to the
      medical schools and related hospitals. More than 60% of the 348 papers are
      affiliated to Al-Arab Medical University, Benghazi, while Al-Fateh Medical
      University, Tripoli, contributed 103 papers (30%). The rest of the papers (n=25,
      7%) were published by medical schools in other parts of the country. The
      publication rate declined by 3% annually between 1988 and 2007. The decline was
      mainly due to a decrease in the publication rate by Al-Arab Medical University,
      Benghazi. Overall, nine departments produced 10 or more papers each. Out of about
      1675 staff members, there are only 148 first authors and 207 last authors. The
      estimated annual publication rate is 0.7 papers per 100 academic staff members.
      CONCLUSION: This study reveals that published scholarship of the Libyan medical
      schools is extremely low, that the publication rate has declined, and that most
      academic staff have no publications listed in PubMed. This issue needs urgent
      attention.

PMID- 20029756
TI  - Making a difference: an interview with Pauline Vluggen.

PMID- 20029757
TI  - Guest editorial: the role and impact of indigenous community health workers.

PMID- 20029758
TI  - Co-editors' notes 22:2.

PMID- 20029759
TI  - Assessing CPR training: The willingness of teaching credential candidates to
      provide CPR in a school setting.
AB  - INTRODUCTION: The study explores the anticipated willingness of teacher
      credential candidates at one California public university in the U.S. to perform
      cardiopulmonary resuscitation (CPR) or foreign body airway obstruction (FBAO)
      skills in a school setting. Objectives included (1) identifying reasons that
      credential candidates would elect or decline to perform CPR, (2) assisting
      schools to remediate cardiac/respiratory emergency preparedness, and (3)
      assessing CPR training courses to determine how they may influence teachers'
      willingness to perform CPR. METHOD: Participants included 582 teacher credential
      candidates, who were 95.2% of those surveyed after completion of a health science
      course and CPR certification. Participants described their attitudes regarding
      the importance of CPR, the CPR training course, and their willingness to perform
      CPR in a school environment. RESULTS: Based upon chi-square analysis, an
      association was found between the willingness to perform CPR and the presence of
      any one concern regarding training, with 68.6% of those expressing concerns
      willing to perform CPR compared to 81.9% of those expressing no concerns
      (p<.0005). Participants certified multiple times stated that they were more
      likely to perform FBAO skills on both conscious (89% vs. 78.9%, p=.025) and
      unconscious victims (80% vs. 72%, p<.001), as were participants who believed CPR
      to be an important skill for teachers (76.9% vs. 43.5%, p<.001). Males were more
      likely to express willingness to perform CPR than females (84.6% vs. 72.1%,
      p<.001). CONCLUSIONS: Attitudes regarding CPR training may influence teachers'
      willingness to perform CPR. Recommendations based on these findings include
      pedagogical changes to CPR curricula, focusing on the importance of CPR as a
      teacher skill and additional time for hands-on practice. Future research should
      include U.S. and international participants from a broader geographic area and
      assessment of both learning and affective outcomes.

PMID- 20029760
TI  - Pedagogical processes in healthcare: an exploratory study of pedagogic work with
      patients and next of kin.
AB  - BACKGROUND: Care and education have much in common, and work in the healthcare
      sector is closely associated with learning and teaching. It is felt that many in
      the healthcare and medical services are not aware of their pedagogic skills and
      how they can be developed. FRAME OF REFERENCE: Belonging to a community of
      practice means that you share perspectives, methods and language. OBJECTIVE: The
      aim is to describe the pedagogical discourse by identifying pedagogical processes
      and studying the staff's awareness of such processes or situations in which a
      pedagogical approach would be useful in their work with patients and next of kin.
      METHOD: A qualitative study based on individual and group interviews. The
      analysis is directed by grounded theory. RESULTS: The pedagogical processes
      varied in length and quality. Most were unplanned and were usually embedded in
      treatment. The pedagogical process is linear (planning, goal setting, teaching
      and evaluating) in an educational setting but we found that the beginning and end
      can be unclear and the goals can be vague or non-existent. The pedagogical
      process is best described using the concepts Read, Guide and Provide learning
      support. DISCUSSION: The pedagogical discourse in healthcare is almost silent.
      Data indicate that at the collective level there is very little support for
      professional development of pedagogical ability. Tacit knowledge may therefore
      remain silent even though it may be possible to formulate and describe it.
      CONCLUSIONS: There is a strong need to focus on the pedagogical parts of the work
      and to encourage and support the development of professional pedagogical
      knowledge.

PMID- 20029761
TI  - Use of community-based participatory research to disseminate baseline results
      from a cardiovascular disease randomized community trial for Mexican Americans
      living in a U.S.-Mexico border community.
AB  - INTRODUCTION: This article describes the development of a community-based
      participatory research (CBPR) process conducted in the context of a randomized
      community health education trial utilizing community health workers (CHWs).
      OBJECTIVES: To present lessons learned from the utilization of CBPR methodology
      in a cardiovascular disease (CVD) prevention trial among Mexican American adults
      in a U.S.-Mexico border community and to disseminate the baseline results
      associated with risk factors for CVD and their associated demographic and
      psychosocial characteristics. METHODS: Participants were 328 Hispanic adults ages
      30-75 with at least one risk factor for CVD (overweight, smoking, high
      cholesterol, diabetic or hypertensive), who were recruited through approaching
      households in randomly selected census tracts within a specified zip code area.
      RESULTS: CBPR methods were applied during the different stages of the research
      enterprise to support the development and implementation of the intervention
      trial aim at reducing cardiovascular risk factors for Mexican American adults.
      Data from baseline were used as an important component of dialogue with the
      community. DISCUSSION: CBPR proved to be a good learning process for all partners
      involved. The risk profile of the participants demonstrated the "epidemic" nature
      of CVD morbidity conditions associated with Mexican origin populations living in
      a U.S.-Mexico border community. The CBPR dialogue was instrumental as a process
      to help disseminate to the community the need for projects like the one described
      in this article.

PMID- 20029762
TI  - Learner-centred medical education: Improved learning or increased stress?
AB  - CONTEXT: Globally, as medical education undergoes significant reform towards more
      "learner-centred" approaches, specific implications arise for medical educators
      and learners. Although this learner-centredness is grounded in educational
      theory, a point of discussion would be whether the application and practice of
      these new curricula alleviate or exacerbate student difficulties and levels of
      stress. OBJECTIVES: This commentary will argue that while this reform in medical
      education is laudable, with positive implications for learning, medical educators
      may not have understood or perhaps not embraced "learner-centredness" in its
      entirety. DISCUSSION: During their training, medical students are expected to be
      "patient-centred". They are asked to apply a biopsychosocial model, which takes
      cognisance of all aspects of a patient's well-being. While many medical schools
      profess that their curricula reflect these principles, in reality, many may not
      always practice what they preach. Medical training all too often remains grounded
      in the biomedical model, with the cognitive domain overshadowing the psychosocial
      development and needs of learners. CONCLUSIONS: Entrusted by parents and society
      with the education and training of future healthcare professionals, medical
      education needs to move to a "learner-centred philosophy", in which the "whole"
      student is acknowledged. As undergraduate and post-graduate students increasingly
      apply their skills in an international arena, this learner-centredness should
      equally encapsulate the gender, cultural and religious diversity of both patients
      and students. Appropriate support structures, role models and faculty development
      are required to develop skills, attitudes and professional behaviour that will
      allow our graduates to become caring and sensitive healthcare providers.

PMID- 20029763
TI  - Communicating across cultures: suggested teaching strategies.
AB  - CONTEXT: Quality healthcare for diverse populations requires providers that
      understand the impact of culture on health and health-seeking behaviors.
      Recruiting individuals from diverse cultures into healthcare professions
      facilitates this understanding. Although nursing education programs have been
      successful in recruiting such individuals, they often experience difficulties
      communicating with faculty and patients, which contributes to attrition from
      their first clinical course. Communicating Across Cultures is an innovative
      learning experience at our school to facilitate achievement of clinical
      competencies in the first nursing course. The purpose of this paper is to
      describe the teaching strategies used in this course that have increased
      achievement of clinical competencies and decreased the attrition rate of students
      from diverse cultures at our school. SUGGESTED TEACHING STRATEGIES: First,
      assessing the students' specific communication difficulties guides what learning
      objectives and content are appropriate. Second, an immersion experience
      immediately before students begin their first clinical course provides
      experiential learning suited to acquiring new communication styles. Third, the
      experience and subsequent reinforcement are facilitated by faculty with expertise
      in teaching communication skills and with guiding the learning experiences of
      students from diverse cultures. Fourth, delineation of eligibility criteria
      allows students to self-identify their need to participate. Finally, an
      evaluation plan provides information to help make decisions about subsequent
      implementation of the learning experience.

PMID- 20029764
TI  - Portfolio assessment during medical internships: How to obtain a reliable and
      feasible assessment procedure?
AB  - BACKGROUND: A portfolio is used to mentor and assess students' clinical
      performance at the workplace. However, students and raters often perceive the
      portfolio as a time-consuming instrument. PURPOSE: In this study, we investigated
      whether assessment during medical internship by a portfolio can combine
      reliability and feasibility. METHODS: The domain-oriented reliability of 61
      double-rated portfolios was measured, using a generalisability analysis with
      portfolio tasks and raters as sources of variation in measuring the performance
      of a student. RESULTS: We obtained reliability (Phi coefficient) of 0.87 with
      this internship portfolio containing 15 double-rated tasks. The generalisability
      analysis showed that an acceptable level of reliability (Phi = 0.80) was
      maintained when the amount of portfolio tasks was decreased to 13 or 9 using one
      and two raters, respectively. CONCLUSIONS: Our study shows that a portfolio can
      be a reliable method for the assessment of workplace learning. The possibility of
      reducing the amount of tasks or raters while maintaining a sufficient level of
      reliability suggests an increase in feasibility of portfolio use for both
      students and raters.

PMID- 20029765
TI  - Evaluation of a workshop to improve community involvement in community-based
      participatory research efforts.

PMID- 20029766
TI  - Faculty as simulated patients (FSPs) in assessing medical students' clinical
      reasoning skills.
AB  - CONTEXT: At the University of Sharjah College of Medicine in the United Arab
      Emirates, clinical faculty are used as simulated patients (FSP) to assess
      students' communication, history taking and reasoning skills on summative
      Objective Structured Clinical Examinations (OSCEs). OBJECTIVES: The aim of this
      study is to evaluate student and faculty perceptions of using a faculty member
      simultaneously as both the simulated patient and the assessor in OSCEs. METHODS:
      Two structured questionnaires were developed. The questionnaires measured, on a
      five-point Likert scale, the students' and faculty's agreement with statements
      related to the ability of the FSPs to convince students that they were real
      patients, to respond to students' questions, and to evaluate students' skills in
      questioning, communication and clinical reasoning. Responses to items were
      collapsed into three-point scales (3=Agree/Strongly Agree, 2=Neutral/Uncertain,
      1=Disagree/Strongly Disagree). Students' and faculty's responses to the
      questionnaires' items were summarized and presented in frequencies, percentages
      and mean scores. FINDINGS: A total of 412 students and 28 FSPs responded to the
      questionnaires with response rates of 98% and 93%, respectively. The encounter
      with a FSP was generally found not to be stressful by students and faculty.
      Students were able to think of the FSP as a real patient and faculty generally
      felt they were able to assess the students' reasoning processes, communication
      skills and history taking. The percentage of students who agreed or strongly
      agreed with the various positively-worded questionnaire items ranged from a
      lowest of 52% (mean = 2.32) to a highest of 78% (mean = 2.66) and among faculty
      ranged from a lowest of 61% (mean = 2.54) to a highest of 100% (mean=3.0).
      CONCLUSION: Student and faculty perceptions about the simultaneous use of faculty
      as simulated patients and assessors were generally positive. The results of this
      study encouraged the program to continue using FSPs on formative and summative
      OSCE assessments. Further studies are needed to assess its generalizability and
      application in other contexts.

PMID- 20029767
TI  - Direct observation of resident-patient encounters in continuity clinic: a
      controlled study of parent satisfaction and resident perceptions.
AB  - CONTEXT: Direct observation (DO) by teaching physicians of medical care provided
      by resident physicians offers a method to evaluate clinical skills beyond
      traditional measures that focus solely on medical knowledge assessment.
      OBJECTIVES: We sought to determine if the presence of the teaching physician
      observer affects parental satisfaction with care and to assess resident
      perceptions of DO in a general pediatrics residency clinic. METHODS: A cross
      sectional parent survey compared visit satisfaction of parents who experienced a
      DO with controls in a traditional clinic visit. Additionally, a pre-post survey
      measured resident perceptions of direct observation before and after
      implementation of DO in the clinic. FINDINGS: Parents frequently described their
      overall satisfaction with care as "excellent" after DO and traditional visits (DO
      70%, 95% CI, 50-86% and control 80%, CI 66-89%). However, parents in DO visits
      were less likely to rate their satisfaction with the amount of time spent in the
      room as excellent (DO 78%, CI 58-91%; Control 95%, CI 85-99%). Most resident
      physicians were in favor of the DO process (63%) and agreed that DO provides
      feedback about history-taking (94%), physical examination (94%) and interpersonal
      skills (91%). CONCLUSIONS: Direct observation by attending physicians does not
      decrease overall parental satisfaction during clinical encounters. Additionally,
      residents have a generally favorable opinion of direct observation and believe
      that it can provide useful feedback.

PMID- 20029768
TI  - Why a medical career and what makes a good doctor? Beliefs of incoming United
      States medical students.
AB  - INTRODUCTION: Beginning medical students' beliefs about the medical profession
      have been well studied internationally but have only been minimally studied in
      the United States (U.S.) recently. Up-to-date research on U.S. medical students'
      beliefs is warranted so educators can employ these predispositions as a baseline
      for curriculum and student professional development. METHODS: We conducted focus
      groups with a first-year class (n=189) of U.S. medical students at the beginning
      of their academic year. In an iterative theming process, investigators worked in
      dyads and subsequently as a group to develop a list of preliminary themes
      expressed in the focus groups. Investigators individually sorted preliminary
      themes into similar categories. All sorted preliminary themes and categories were
      placed in a matrix from which final themes were derived. FINDINGS: Investigators
      found eight themes for the question "Why pursue a career in medicine?" and six
      themes for "What makes a good doctor?". Students expected medicine to be
      intellectually and personally fulfilling, they expected to be respected by the
      community, indicated that early experiences with medicine impacted their career
      choices, and anticipated that a medical career would yield financial security. A
      good doctor was described as a committed, smart, decisive leader who
      enthusiastically partners with patients via effective interpersonal skills.
      DISCUSSION: Beginning U.S. medical students hold multi-faceted beliefs about
      medicine that are similar to international medical students' beliefs. Themes
      related to patient-centeredness, decisive leadership, and intellectual curiosity
      have particular utility in curriculum and professional development and should not
      be ignored. Administrators seeking to expand the physician workforce should
      consider early experiences, status, and monetary rewards.

PMID- 20029769
TI  - Process and outcome evaluation of a diabetes prevention education program for
      community healthcare workers in Thailand.
AB  - OBJECTIVE: To describe the development, process and outcome evaluation of a
      culturally tailored diabetes prevention education program for community
      healthcare workers (CHCWs) in Thailand. METHODS: A tailored diabetes prevention
      education program was designed based on formative research and implemented with
      35 CHCWs in semi-urban areas in Chiang Mai province, Thailand. Modules were
      delivered over eight group classes and eight self-directed E-learning sessions
      (www.FitThai.org). The program incorporated problem-based learning, discussion,
      reflection, community-based application, self-evaluation and on-line support. The
      frequency that students accessed on-line materials, including videotaped
      lectures, readings, monthly newsletters and community resources, was documented.
      Participant satisfaction was assessed through three questionnaires. Knowledge was
      assessed through pre-post testing. RESULTS: Three-quarters of participants
      attended all eight classes and no participant attended fewer than six. On-line
      support and materials were accessed 3 to 38 times (median 13). Participants
      reported that program information and activities were fun, useful, culturally
      relevant and applicable to diabetes prevention in their specific communities.
      Participants also appreciated the innovative technology support for their work.
      Comfort with E-learning varied among participants. Scores on pre-post knowledge
      test increased from a mean (sd) of 56.5% (6.26) to 75.5% (6.01) (p < .001).
      CONCLUSIONS: An innovative diabetes prevention education program was developed
      for CHCWs in Thailand. Interactive classroom modules and self-directed E-learning
      were generally well-received and supported better knowledge scores. Ongoing
      access to web-based materials and expert support may help sustain learning.

PMID- 20029770
TI  - The observer program: insights from international medical graduates.
AB  - CONTEXT: This paper presents the findings of qualitative research documenting the
      experiences in the Observer Program (OP) from the perspectives of international
      medical graduates (IMGs) entering the Australian healthcare system. OBJECTIVES:
      To examine the experience of IMGs participating in the OP. METHODS: In-depth,
      open-ended interviews were conducted with nine IMGs who had been part of the OP.
      FINDINGS: The feedback provided by the IMG participants about the OP was
      overwhelmingly positive. Participants identified a strong need for such a
      program, both from the perspective of increasing their confidence and competence
      and integrating them into and lifting their status within the Australian
      healthcare system. Positive outcomes reported to result from the program included
      increased confidence as a doctor in Australia, development of a sound knowledge
      of the Australian medical system, including basic medications used in local
      practice, familiarity with appropriate paperwork and the specialties of
      particular physicians, increased experience, refreshment of existing clinical
      skills and the opportunity to learn Australian idioms. However, some participants
      related difficulties created by their unpaid tenure whilst undergoing the
      program, as well as difficulties in relationships with particular supervising
      physicians within the program. DISCUSSION: Findings provide insights into a
      hospital-based educational initiative designed to integrate IMGs into the
      Australian healthcare system. CONCLUSIONS: Responses from participants offer
      practical insights into the need for, strengths, weaknesses and outcomes of the
      OP.

PMID- 20029771
TI  - Making a difference: an interview with Rita Giacaman. Working for health in the
      occupied palestinian territory. Interviewed by Jane Westberg.

PMID- 20029772
TI  - Network: TUFH position paper. The ultimate challenge? Higher education for
      adapting to change and participating in managing change.

PMID- 20029773
TI  - Pauline Vluggen has, indeed, made a difference.

PMID- 20029774
TI  - Renewed focus on Primary Health Care (PHC).

PMID- 20029775
TI  - Co-editors' notes 22:3.

PMID- 20029776
TI  - [FUO: fever of unknown origin].

PMID- 20029777
TI  - [CME ultrasound diagnosis 31. Renal colic: and the anamnesis?].

PMID- 20029778
TI  - [Comment on rule of thumb 6 in Praxis no. 16. Cough and rhinitis: no Strep A
      angina].

PMID- 20029780
TI  - [Prison violence: prevalence, manifestation and risk factors].
AB  - When comparing different studies on prison violence, it must be taken into
      account that correctional facilities vary considerably among one another. Studies
      conducted in Switzerland have shown that every one inmate in four is violent at
      least once during incarceration. These violent acts differ in regard to
      manifestation and a specific characterization of violence according to type,
      target, implication and trigger appears to be necessary. Existing criminal
      prognostic instruments are not suitable for estimating the risk of violent
      behavior in prisons. Therefore, the development of specific models is essential.
      International studies have identified various risk factors. However, due to the
      aforementioned differences in facilities, these predictors can only partly be
      transferred to a Swiss setting.

PMID- 20029781
TI  - [Stroke].
AB  - Ischemic stroke is a very frequent neurological disorder. It's incidence is
      increasing as western societies are aging. Effective therapies that reduce
      mortality and increase the chances of living symptom-free or, at least, in
      independence are available. Intravenous or intraarterial thrombolysis is an
      effective treatment with a number needed to treat of 6 if given within 4.5 hours
      after symptom onset. The safe use of thrombolysis requires an effective and
      repeatedly trained workflow established within a team of a neurologist and
      specialized nursing staff in an optimized environment (admission, imaging
      facility, laboratory, stroke unit). After peracute treatment, the patient should
      be transferred to a stroke unit. This unit is a spatially defined intermediate
      care unit with specifically trained personnel (physicians, nurses, therapists).
      Treating the patient in a stroke unit is as effective in improving outcome as
      thrombolysis and also reduces the length of hospital stay. In contrast to
      thrombolysis, which can be provided, on average, to only 5% of stroke patients,
      stroke unit care is applicable to most. The organization of medical care in most
      European countries and in Switzerland separate the acute phase from subacute
      rehabilitation and chronic stroke treatment. This can be highly confusing for the
      patient who, during the course of the disease, meets different physicians, nurses
      and therapists with often diverging opinions about prognosis and therapies.
      Consistent treatment approaches and patient/caregiver information is necessary
      and can only be implemented by providing a homogeneous pathway for continuous
      stroke care.

PMID- 20029782
TI  - [Nuclear medicine diagnosis of bone metastases].
AB  - Conventional bone scintigraphy is still the standard investigation for the
      detection of bone metastases, especially in breast and prostate cancer. In
      unclear scintigraphic uptakes in the appendicular skeleton conventional x-rays
      are problem solving in most of the cases. In unclear uptakes in the axial
      skeleton additional performance of SPECT/CT can increase the specificity.
      Fluoride-PET/CT is superior to conventional bone scintigraphy but is not yet
      available in clinical routine. Patients with high-risk breast cancer and patients
      with lung cancer should be staged with FDG-PET/CT primarily. An additional bone
      scan is than superfluous. The great advantage of FDG-PET/CT is the fact that bone
      metastases and organ metastases can be detected in the same investigation. There
      is a clear trend of shifting patients from conventional nuclear medicine to
      PET/CT.

PMID- 20029783
TI  - [Ethyl glucuronide: a biomarker of alcohol consumption].
AB  - Excessive alcohol consumption represents a major risk factor for morbidity and
      mortality. It is therefore indispensable to be able to detect at-risk drinking.
      Ethyl glucuronide (EtG) is a specific marker of alcohol consumption. The
      determination of ethyl glucuronide in urine or blood can be used to prove recent
      driving under the influence of alcohol, even if ethanol is no longer detectable.
      The commercialization of an EtG specific immunological assay now allows to obtain
      preliminary results rapidly and easily with satisfying sensitivity. Moreover, the
      detection of ethyl glucuronide in hair offers the opportunity to evaluate an
      alcohol consumption over a long period. The EtG concentration in hair is in
      correlation with the amount of ingested alcohol. Thus, the analysis of ethyl
      glucuronide can be used to monitor abstinence, to detect alcohol relapse and to
      identify at-risk drinkers. However, a cut off allowing to detect chronic alcohol
      abuser reliably still does not exist. Therefore, it is recommended to perform the
      analysis of ethyl glucuronide in complement to the existing blood markers. A
      study financed by the Swiss Foundation for Alcohol Research is actually conducted
      by the West Switzerland University Center of Legal Medicine in order to establish
      an objective cut-off.

PMID- 20029784
TI  - [Acne vulgaris].

PMID- 20029785
TI  - [Coma after lucid interval--severe secondary alteration of consciousness
      following multiple trauma].
AB  - A 71-year-old man sustains multiple fractures in an accident; after a lucid
      interval he deteriorates neurologically and becomes comatose. Intracranial
      hemorrhage, status epilepticus, adverse drug reactions, toxic-metabolic, ischemic
      or infectious causes are subsequently ruled out. Development of petechiae and
      thrombopenia raises the possibility of fat embolism syndrome, which is confirmed
      in a MRI of the head 72 hours after the accident. We discuss current aetiologic
      concepts as well as diagnosis and clinical course of the cerebral fat embolism
      syndrome.

PMID- 20029786
TI  - [Aspirin for the prevention of cardiovascular events in patients with peripheral
      artery disease].

PMID- 20029787
TI  - [Compression stockings do not reduce the risk of deep vein thrombosis in patients
      after stroke].

PMID- 20029794
TI  - Olanzapine monotherapy for acute depression in patients with bipolar I or II
      disorder: results of an 8-week open label trial.
AB  - We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in
      20 adult patients with bipolar I or II disorder, depressed phase. Patients
      received open-label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8
      weeks. Assessments of psychopathology (Montgomery-Asberg Depression Rating Scale
      [MADRS], Quick Inventory of Depressive Symptomatology [QIDS-SR-16], Young Mania
      Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI]
      scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6,
      and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS
      total scores was observed after the first week of treatment, and at all remaining
      follow-up time points (p < or = 0.005). Parallel improvement in QIDS-SR-16 (p <
      0.001) and CGI-Severity (p < 0.001) was observed between baseline and study
      endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom
      (40%) also achieved symptom remission. There were significant increases in weight
      (+3.2 kg, p = 0.001) and body mass index (+1.1 kg/m(2), p = 0.001), but not
      fasting glucose or lipids, with the exception of reduced triglyceride levels in
      the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an
      effective, well-tolerated option for treating acute non-psychotic depression
      across a variety of bipolar disorder subtypes.

PMID- 20029795
TI  - Reliability and validity of the PHQ-9 for screening late-life depression in
      Chinese primary care.
AB  - OBJECTIVE: The aim of this study was to examine the reliability and validation of
      the 9-item Patient Health Questionnaire (PHQ-9) for late-life depression in
      Chinese primary care. METHODS: In the primary care clinics (PCCs) of Hangzhou
      city, we recruited 364 older patients (aged >= 60) for the PHQ-9 screening. Then
      77 of them were further interviewed with Structured Clinical Interview for DSM
      Disorders (SCID) for the diagnosis of major depression in late life. Statistic
      strategies for the feasibility, reliability, validity, and receiver operating
      characteristic curve were performed. RESULTS: The mean administration time was
      7.5 min, and the Cronbach's alpha was 0.91. The optimal cut-off score of PHQ-9 >=
      9 revealed a sensitivity of 0.86, specificity of 0.77, and positive likelihood
      ratio of 5.73. The area under the curve (AUC) in this study was 0.92 (SD = 0.02,
      95% CI 0.88-0.96). The PHQ-2 also revealed good sensitivity (0.84) and
      specificity (0.90) at the cut-off point >= 3. CONCLUSIONS: The PHQ-9 performs
      well and has acceptable psychometric properties for screening of patients with
      late-life depression in Chinese primary care settings.

PMID- 20029796
TI  - A case-control study of risk factors for hepatitis B virus infection in North
      Jordan.
AB  - Jordan is a country with intermediate endemicity for hepatitis B virus (HBV)
      infection where risk factors for viral transmission and their relative
      contributions are not well known. A case-control study of 100 hepatitis B virus
      seropositive patients and another 100 seronegative controls was conducted.
      Univariate analysis and logistic regression model were performed to examine
      probable risk factors for acquisition of hepatitis B virus infections. Logistic
      regression analysis showed that significant risk factors for acquisition of
      hepatitis B virus infection were sharing toothbrushes (odds ratio = 10.167; 95%
      confidence interval, 1.181-87.509), unhygienic dental care (odds ratio = 2.455;
      95% confidence interval, 1.294-4.658), and living abroad for at least 1 year
      (odds ratio = 20.018; 95% confidence interval, 2.268-176.685). The presence of
      these risk factors emphasizes the need for both increasing the use of hepatitis B
      vaccines and risk-targeted public health education. Development and enforcement
      of appropriate infection control guidelines for dental care services are also
      necessary to curtail HBV transmission. Further research that controls for
      confounding factors is needed to assess the relative contribution of the
      identified risk factors in the Jordanian community.

PMID- 20029797
TI  - Determination of rubella virus-specific cell-mediated immunity using IFN gamma
      ELISpot.
AB  - Immunity to rubella virus (RV) is conventionally determined by measuring specific
      immunoglobulin G (IgG). However, several individuals may be considered immune
      despite undetectable antibody levels. In the present study RV-specific interferon
      gamma (IFN gamma)-ELISpot and rubella-IgG-ELISA were compared in 75 young adults
      aged between 20 and 30 years. In a subgroup, not only rubella-like particles
      (RLP), but also HPV77 rubella vaccine derived antigen was used in IFN gamma
      ELISpot. The results from both, ELISA and ELISpot were independent of previous
      encounter to RV (vaccination, exanthematous disease, or childhood infection).
      There was no difference between RLP and RV vaccine antigen in IFN gamma-ELISpot
      response, and there was no correlation between IFN gamma-ELISpot and RV-specific
      IgG levels. IFN gamma-producing cells were found in 78.7% of all tested persons,
      and 83.8% of them were positive in ELISA. In almost all individuals seronegative
      for RV antibody, IFN gamma-producing cells were detected. Considering both
      humoral and cell-mediated immune responses, a positive RV immune reaction was
      seen in 98.6%. The results indicate that the IFN gamma-ELISpot can provide
      valuable additional information in seronegative individuals.

PMID- 20029798
TI  - Sustained low-dose growth hormone therapy optimizes bioactive insulin-like growth
      factor-I level and may enhance CD4 T-cell number in HIV infection.
AB  - High-dose recombinant human growth hormone (rhGH) (2-6 mg/day) regimes may
      facilitate T-cell restoration in patients infected with human immunodeficiency
      virus (HIV) on highly active antiretroviral therapy (HAART). However, high-dose
      rhGH regimens increase insulin-like growth factor-I (IGF-I) to supra
      physiological levels associated with severe side effects. The present study
      investigated whether lower doses of rhGH may improve T-cell restoration in
      patients infected with HIV following an expedient response of total and bioactive
      (i.e., free) IGF-I. A previous 16-week pilot-study included six HIV-infected
      patients on stable HAART to receive rhGH 0.7 mg/day, which increased total
      (+117%, P < 0.01) and free (+155%, P < 0.01) IGF-I levels. The study was extended
      to examine whether continuous use of low-dose rhGH (0.7 mg/day until week 60; 0.4
      mg/day from week 60 to week 140) would maintain expedient IGF-I levels and
      improve CD4 T-cell response. Total and free IGF-I increased at week 36 (+97%, P <
      0.01 and +125%, P < 0.01, respectively) and week 60 (+77%, P = 0.01 and +125%, P
      < 0.01) compared to baseline levels (161 +/- 15 and 0.75 +/- 0.11 microg/L). CD4
      T-cell number increased at week 36 (+15%, P < 0.05) and week 60 (+31%, P = 0.01)
      compared to baseline levels (456 +/- 55 cells/microL). Following rhGH dose
      reduction, total IGF-I and CD4 T-cell number remained increased at week 88 (+44%,
      P = 0.01 and +33%, P < 0.01) and week 140 (+46%, P = 0.07 and +36%, P = 0.02)
      compared to baseline levels. These data support the notion that low-dose rhGH
      regimens may increase expediently total and bioactive IGF-I and improve T-cell
      restoration in patients infected with HIV on HAART.

PMID- 20029799
TI  - Hepatitis C virus recombinants are rare even among intravenous drug users.
AB  - Systematic studies of the circulation of hepatitis C virus (HCV) recombinants in
      different parts of the world have been initiated only recently, and no detailed
      information on this subject is available. The aim of the current investigation
      was to determine the frequency of HCV recombinants in intravenous drug users
      (IVDU) from two European countries. HCV RNA from serum samples was tested by RT
      PCR with primers derived from the core and NS5B regions with subsequent
      sequencing and genotype assignment. The 118 samples from Germany (100%) and 45
      out of 47 (96%) sera from Russia demonstrated concordant genotyping results. In
      the two genotype discrepant sera from Russia 2k/1b recombinants were identified.
      In order to test the hypothesis that the individuals from the IVDU group might be
      multiply exposed to various genotypes, 145 out of 165 genotyped serum samples,
      which were found to be positive for anti-NS4 antibodies, were serotyped with the
      Murex HCV serotyping kit that is based on detection of antibodies to type
      specific peptides derived from the NS4 proteins of different HCV genotypes.
      Discrepancy in genotype and serotype attributions was observed in 11% cases.
      Retesting of 99 type 1a or 3a samples with a set of type- and subtype-specific
      primers revealed the presence of a mixed infection only in one case (1a/3a).
      Thus, the cases of the mixed infection with different HCV genotypes as well as
      the recombinant forms of HCV are very rare even in such a highly exposed group as
      IVDU.

PMID- 20029800
TI  - High circulating levels of N-terminal pro-brain natriuretic peptide and
      interleukin 6 in patients with mixed cryoglobulinemia.
AB  - Many patients with mixed cryoglobulinemia and chronic HCV infection experience
      symptoms, such as dyspnea, which sometimes do not seem to indicate the
      involvement of the liver but rather the symptoms of heart failure. To our
      knowledge, there has been no other study evaluating the serum levels of N
      terminal pro-brain natriuretic peptide (NTproBNP) and Interleukin 6 (IL-6) in
      such patients. Serum NTproBNP and IL-6 were assayed in 54 patients with mixed
      cryoglobulinemia and chronic HCV infection, and in 54 sex- and age-matched
      controls. Cryoglobulinemic-patients showed significantly higher mean NTproBNP and
      IL-6 levels than the controls (P = 0.005). By defining a high NTproBNP level as a
      value higher than 125 pg/ml (the single cut-off point for patients under 75 years
      of age), 30% of patients with mixed cryoglobulinemia and chronic HCV infection
      and 7% of controls had high NTproBNP (chi-square; P < 0.003). With a cut-off
      point of 300 pg/ml (used to rule out heart failure in patients under 75 years of
      age), 5/49 patients with mixed cryoglobulinemia and chronic HCV infection and
      0/54 controls had high NTproBNP (chi-square; P < 0.04). With a cut-off point of
      900 pg/ml (used for including heart failure in patients aged between 50 and 75,
      such as the patients in this study) 3/51 of patients with mixed cryoglobulinemia
      and chronic HCV infection and 0/54 controls had high NTproBNP (chi-square; P =
      0.07). The study revealed high levels of circulating NTproBNP and IL-6 in
      patients with mixed cryoglobulinemia and chronic HCV infection. The increase in
      NTproBNP could indicate the presence of a subclinical cardiac dysfunction.

PMID- 20029801
TI  - Genetic polymorphism at the apolipoprotein E locus affects the outcome of chronic
      hepatitis B.
AB  - Apolipoprotein E (ApoE) and H (ApoH) genotypes are known to affect plasma
      lipoprotein concentrations. By modulating transport and entry of the hepatitis B
      virus into hepatocytes, apolipoproteins may influence the course of infection. To
      verify this hypothesis, 105 patients with chronic HBV infection were examined.
      Sixty-two of the patients were followed-up for a median time of 21 years. One
      hundred two controls were included. ApoE and ApoH genotypes were determined by
      the restriction fragment length polymorphism method. A trend was found for
      progressive overrepresentation of ApoE3/E3 among patients with advanced liver
      disease: 13/27 (48%) of inactive HBV carriers, 36/61 (59%) of chronic hepatitis B
      patients and 16/17 (94%) of patients who received liver transplants (P < 0.005).
      Being an E3/* carrier was associated with a lower probability of loss of HBsAg:
      9/56 (16%) versus 3/6 (50%) (P < 0.05); it was also associated with a longer time
      before HBsAg loss (P < 0.05). No influence of ApoH genotypes on clinical outcomes
      was found. The probability of disease progression was higher, and that of loss of
      HBsAg was lower, among patients with the ApoE3 allelic variant. Downregulation
      and/or reduced binding of the LDL receptor may explain the more benign course of
      hepatitis B among carriers of ApoE2-E4.

PMID- 20029802
TI  - Hepatitis C virus core protein enhances Telomerase activity in Huh7 cells.
AB  - Hepatitis C is an oncogenic virus although the mechanisms responsible for this
      behavior are not clear. We studied the effects of hepatitis C virus (HCV) core
      protein expression on Telomerase, an enzyme closely associated with cellular
      immortalization and neoplasia. The aim of this study was to investigate the
      effects of HCV core protein on the regulation of Telomerase activity in human
      hepatoma cells. Regulation and expression of human Telomerase reverse
      transcriptase (TERT) was compared in Huh7 cells stably transfected with HCV core
      protein or cells expressing vector alone. Telomerase activity was measured using
      Quantitative Telomerase Detection (QTD) and telomere length was measured by
      fluorescence in situ hybridization (FISH). Transient transfection and luciferase
      assay were used to evaluate TERT promoter activity. Telomerase activity was
      increased twofold in Huh7 cells expressing HCV core protein compared to controls
      (P < 0.01). This was accompanied by a 1.4-fold increase of TERT mRNA and 1.9-fold
      increase in TERT protein (P < 0.01 in either case). Cellular fractionation and
      immunocytochemical studies showed increased localization of TERT in the nucleus
      of core-expressing cells as compared to controls. FISH assay confirmed that
      telomeres of HCV core-expressing Huh7 cells were relatively longer than those of
      control cells (0.22 + 0.05 vs. 0.12 + 0.03, P < 0.01). TERT promoter activity was
      enhanced about 30% in HCV core-expressing Huh7 cells compared to control cells (P
      < 0.02). HCV core protein is associated with increased Telomerase activity in
      hepatoma cells. These findings suggest that enhancement of Telomerase activity by
      HCV core protein may contribute to the oncogenicity of HCV.

PMID- 20029803
TI  - No evidence of porcine endogenous retrovirus in patients with type 1 diabetes
      after long-term porcine islet xenotransplantation.
AB  - Xenotransplantation is a promising alternative for donor shortage to ameliorate
      physiologic and metabolic disorders. The major concern for xenotransplant is the
      risk of zoonosis mainly by the porcine endogenous retrovirus (PERV), presentation
      in the piglet genome. Twenty-three patients with type 1 diabetes were
      transplanted with porcine islets using collagen-generating devices which were
      implanted subcutaneously in the anterior wall of the abdomen. Clinical
      characteristics and metabolic tests were recorded in each visit. They were tested
      for PERV using PCR and RT-PCR from blood pretransplantation and every 3 months
      during a 4.6- to 8-year follow-up after their first xenotransplant. Tests by PCR
      of every DNA sample (780 samples) revealed that there was no PERV infection in
      the DNA of white cells. No evidence of PERV activation was found in this group of
      patients with type 1 diabetes during clinical long-term follow-up.

PMID- 20029804
TI  - Improving on analyses of self-reported data in a large-scale health survey by
      using information from an examination-based survey.
AB  - Common data sources for assessing the health of a population of interest include
      large-scale surveys based on interviews that often pose questions requiring a
      self-report, such as, 'Has a doctor or other health professional ever told you
      that you have health condition of interest?' or 'What is your (height/weight)?'
      Answers to such questions might not always reflect the true prevalences of health
      conditions (for example, if a respondent misreports height/weight or does not
      have access to a doctor or other health professional). Such 'measurement error'
      in health data could affect inferences about measures of health and health
      disparities. Drawing on two surveys conducted by the National Center for Health
      Statistics, this paper describes an imputation-based strategy for using clinical
      information from an examination-based health survey to improve on analyses of
      self-reported data in a larger interview-based health survey. Models predicting
      clinical values from self-reported values and covariates are fitted to data from
      the National Health and Nutrition Examination Survey (NHANES), which asks self
      report questions during an interview component and also obtains clinical
      measurements during a physical examination component. The fitted models are used
      to multiply impute clinical values for the National Health Interview Survey
      (NHIS), a larger survey that obtains data solely via interviews. Illustrations
      involving hypertension, diabetes, and obesity suggest that estimates of health
      measures based on the multiply imputed clinical values are different from those
      based on the NHIS self-reported data alone and have smaller estimated standard
      errors than those based solely on the NHANES clinical data. The paper discusses
      the relationship of the methods used in the study to two-phase/two
      stage/validation sampling and estimation, along with limitations, practical
      considerations, and areas for future research.

PMID- 20029805
TI  - Recombination of human papillomavirus-16 and host DNA in exfoliated cervical
      cells: a pilot study of L1 gene methylation and chromosomal integration as
      biomarkers of carcinogenic progression.
AB  - Human papillomavirus-16 DNA replicates in productive infections in circular form,
      but is found in most carcinomas integrated into the host cell DNA. Because this
      transition is essential for carcinogenesis, detailed research is desirable and
      may help to triage patients with abnormal Pap smears. Previous studies addressed
      the chromosomal integration of HPV-16 DNA in biopsies of tumors by an indirect
      biomarker, methylation of the viral L1 gene and by reverse ligation polymerase
      chain reaction (rliPCR). The pilot study reported here asked whether these
      techniques can be targeted successfully at DNA prepared from exfoliated cervical
      cells. Abnormal Pap smears of 21 patients that were positive for HPV-16 were
      analyzed for (i and ii) methylation of the L1 gene after bisulfite modification
      and PCR amplification by direct sequencing and indirectly in cloned DNA and (iii)
      recombination with chromosomal DNA by rliPCR. Four of these 21 patients contained
      highly methylated L1 DNA, which was integrated in three of the samples with
      sufficient DNA for rliPCR analysis. Seven patients contained sporadically
      methylated L1 DNA, which was integrated in two and episomal in three samples with
      sufficient DNA. Ten patients contained only unmethylated DNA, which was episomal
      in six but possibly integrated in two samples. It is concluded that HPV-16 is
      found integrated chromosomally in a fraction of precancerous infections, and with
      higher frequency in methylated than in low or unmethylated samples. Since L1 gene
      methylation indicates integration, it has the potential to be used as a clinical
      marker of cancer progression.

PMID- 20029806
TI  - Institutional outbreak of rubella in a healthcare center in Chandigarh, North
      India.
AB  - Rubella is traditionally considered a childhood disease but it has the potential
      to cause outbreaks in closed communities when a susceptible population
      accumulates. The present study reports an outbreak of rubella among healthcare
      workers in the pediatric center of a tertiary care North Indian hospital. The
      cases of rubella were identified by clinical features and confirmed by the
      detection of anti-rubella IgM antibodies in blood by enzyme linked immunosorbent
      assay. A total of 23 cases of rubella occurred over a period of one and a half
      month, out of which 9 (39%) were males. All the patients were in the age group of
      21-35 years. None of the patients gave a history of rubella vaccination. This
      outbreak of rubella occurred due to the accumulation of a susceptible population
      in a closed hospital environment. There is need for the introduction of rubella
      vaccination in healthcare workers to prevent outbreaks at work place.

PMID- 20029807
TI  - Immunomodulatory cytokines determine the outcome of Japanese encephalitis virus
      infection in mice.
AB  - Japanese encephalitis virus (JEV) induces an acute infection of the central
      nervous system, the pathogenic mechanism of which is not fully understood. To
      investigate host response to JEV infection, 14-day-old mice were infected via the
      extraneural route, which resulted in encephalitis and death. Mice that received
      JEV immune splenocyte transfer were protected from extraneural JEV infection.
      Pathology and gene expression profiles were then compared in brains of mice that
      either succumbed to JEV infection or were protected from infection by JEV immune
      cell transfer. Mice undergoing progressive JEV infection had increased expression
      of proinflammatory cytokines, chemokines, and signal transducers associated with
      the interferon (IFN) pathway. In contrast, mice receiving immune cell transfer
      had increased production of the Th2 cytokine IL-4, and of IL-10, with subdued
      expression of IFN-gamma. We observed IL-10 to be an important factor in
      determining clinical outcome in JEV infection. Data obtained by microarray
      analysis were further confirmed by quantitative RT-PCR. Together, these data
      suggest that JEV infection causes an unregulated inflammatory response that can
      be countered by the expression of immunomodulatory cytokines in mice that survive
      lethal infection.

PMID- 20029808
TI  - Human bocavirus infection in young children with acute respiratory tract
      infection in Lanzhou, China.
AB  - Human bocavirus (HBoV) is a recognized human parvovirus associated with acute
      respiratory tract infection. However, HBoV has yet to be established as a
      causative agent of respiratory disease. In this study, the epidemiological and
      virological characteristics of HBoV infection were studied in children with acute
      respiratory tract infection in China. In total, 406 children younger than 14
      years of age with acute respiratory tract infection were included in this
      prospective 1-year study. HBoV was detected in 29 (7.1%) of the 406 children. No
      clear seasonal fluctuation was observed in infection rates of HBoV. Of the 29
      children infected with HBoV, 16 (55.2%) were coinfected with other respiratory
      viruses, most commonly respiratory syncytial virus (RSV). Viral coinfection with
      HBoV did not affect the severity of the respiratory disease (P = 0.291). The
      number of HBoV genome copies ranged from 5.80 x 10(2) to 9.72 x 10(8) copies/ml
      in nasopharyngeal aspirates among HBoV-positive specimens by real-time PCR, and
      neither coinfection nor the severity of disease correlated with the viral load (P
      = 0.148, P = 0.354, respectively). The most common clinical features were cough
      and acute upper respiratory infection, and acute bronchopneumonia. Additionally,
      the NP-1 gene of HBoV showed minimal sequence variation. These data suggest that
      HBoV is frequent in young children with acute respiratory tract infection in
      Lanzhou, China, and RSV is the most common coinfecting virus. There was no
      apparent association between the viral load of HBoV and coinfection or disease
      severity. The NP-1 gene was highly conserved in HBoV.

PMID- 20029809
TI  - Hepatitis C infection among intravenous drug users attending therapy programs in
      Cyprus.
AB  - The most high-risk population for HCV transmission worldwide today are
      intravenous drug users. HCV genotypes in the general population in Cyprus
      demonstrate a polyphyletic infection and include subtypes associated with
      intravenous drug users. The prevalence of HCV, HBV, and HIV infection, HCV
      genotypes and risk factors among intravenous drug users in Cyprus were
      investigated here for the first time. Blood samples and interviews were obtained
      from 40 consenting users in treatment centers, and were tested for HCV, HBV, and
      HIV antibodies. On the HCV-positive samples, viral RNA extraction, RT-PCR and
      sequencing were performed. Phylogenetic analysis determined subtype and any
      relationships with database sequences and statistical analysis determined any
      correlation of risk factors with HCV infection. The prevalence of HCV infection
      was 50%, but no HBV or HIV infections were found. Of the PCR-positive samples,
      eight (57%) were genotype 3a, and six (43%) were 1b. No other subtypes,
      recombinant strains or mixed infections were observed. The phylogenetic analysis
      of the injecting drug users' strains against database sequences observed no
      clustering, which does not allow determination of transmission route, possibly
      due to a limitation of sequences in the database. However, three clusters were
      discovered among the drug users' sequences, revealing small groups who possibly
      share injecting equipment. Statistical analysis showed the risk factor associated
      with HCV infection is drug use duration. Overall, the polyphyletic nature of HCV
      infection in Cyprus is confirmed, but the transmission route remains unknown.
      These findings highlight the need for harm-reduction strategies to reduce HCV
      transmission.

PMID- 20029810
TI  - Detection of varicella-zoster virus DNA in 414 human trigeminal ganglia from
      cadavers by the polymerase chain reaction: a comparison of the detection rate of
      varicella-zoster virus and herpes simplex virus type 1.
AB  - Investigation of varicella-zoster virus (VZV) is important epidemiologically, and
      determination of its prevalence rate in human trigeminal ganglia is important to
      provide surveillance data. To date, studies on VZV detection in trigeminal
      ganglia have used specimens obtained from a relatively limited number of
      cadavers. This study attempted to detect VZV DNA as well as Herpes simplex virus
      type 1 (HSV-1) DNA by the polymerase chain reaction (PCR) from 414 samples of
      trigeminal ganglia obtained from 207 cadavers selected at random. The detection
      rate was examined to determine whether there were significant differences in the
      positive rate between the left and right trigeminal ganglia, males and females,
      and among age groups. A relationship was found between the positive rates for VZV
      and HSV-1. VZV DNA was detected in 391 of the trigeminal ganglia (94.4%) and 201
      of the cadavers (97.1%) in 121/124 males and 80/83 females. HSV-1 DNA was
      detected in 251 of the samples (60.6%) and 134 of the cadavers (64.7%) in 72/124
      males and 62/83 females. There was no significant difference for either virus in
      the detection rates between the left and right trigeminal ganglia and males and
      females. Age and positivity for HSV-1, but not VZV, showed a significant
      relationship. All 134 cadavers positive for HSV-1 were also positive for VZV. VZV
      and HSV-1 become latent in bilateral trigeminal ganglia, and are not affected by
      gender. The prevalence of HSV-1 was greater in advanced age, and the HSV-1
      positive rate was correlated with the VZV-positive rate.

PMID- 20029812
TI  - Monitoring hepatitis C infection in a major Swedish nephrology unit and molecular
      resolution of a new case of nosocomial transmission.
AB  - Hepatitis C virus (HCV) infection is a frequent problem in hemodialysis units.
      The prevalence and incidence of HCV infection over a decade were studied in a
      nephrology unit affected by previous nosocomial HCV transmission. The HCV non
      structural 5B protein gene was sequenced to achieve phylogenetic analysis of a
      new (incident) case of infection. Proportions of patients who were and were not
      infected with HCV remained similar over the period, as did the inflow and outflow
      of patients infected previously. In 1997, 12/157 (8%) of patients at the unit
      (treatment: hemodialysis, peritoneal dialysis, and renal transplant recipients)
      were positive in HCV RNA, whereas in 2007 the overall number was 9/239 (4%). One
      patient acquired an HCV infection, and the NS5B sequence in that case clustered
      with genotype 2b sequences found in patients from an earlier outbreak. Comparing
      the HCV from the incident patient with several stored longitudinal samples and
      cloned PCR products from the most likely source patient revealed close
      phylogenetic relationship with an HCV quasispecies member from the possible
      source. The source patient and the incident newly infected patient were not
      scheduled on the same dialysis shift, although the records showed that
      simultaneous treatment occurred on two occasions during the months preceding
      transmission. In conclusion, over the 10-year period, the proportion of HCV
      infected patients at the unit was unchanged. Only one new infection occurred,
      which originated from a fellow patient's quasispecies. This establishes
      phylogenetic analysis as a valuable tool for tracing patient sources of HCV
      transmission.

PMID- 20029811
TI  - Geographic distribution of hepatitis C virus genotype 6 subtypes in Thailand.
AB  - The nucleotide sequence of hepatitis C virus (HCV) genotype 6 found mostly in
      south China and south-east Asia, displays profound genetic diversity. The aim of
      this study to determine the genetic variability of HCV genotype 6 (HCV-6) in
      Thailand and locate the subtype distribution of genotype 6 in various geographic
      areas. Four hundred nineteen anti-HCV positive serum samples were collected from
      patients residing in - the central part of the country. HCV RNA positive samples
      based on reverse transcriptase- polymerase chain reaction (RT-PCR) of the 5'UTR
      were amplified with primers specific for the core and NS5B regions. Nucleotide
      sequences of both regions were analyzed for the genotype by phylogenetic
      analysis. To determine geographic distribution of HCV-6 subtypes, a search of the
      international database on subtype distribution in the respective countries was
      conducted. Among 375 HCV RNA positive samples, 71 had HCV-6 based on phylogenetic
      analysis of partial core and NS5B regions. The subtype distribution in order of
      predominance was 6f (56%), 6n (22%), 6i (11%), 6j (10%), and 6e (1%). Among the
      13 countries with different subtypes of HCV-6, most sequences have been reported
      from Vietnam. Subtype 6f was found exclusively in Thailand where five distinct
      HCV-6 subtypes are circulating. HCV-6, which is endemic in south China and south
      east Asia, displays profound genetic diversity and may have evolved over a
      considerable period of time.

PMID- 20029813
TI  - Sequence variations of the VP1 gene of Polyomavirus hominis 1 among Bulgarians.
AB  - Polyomavirus hominis 1 (BK virus, BKV) is an important pathogen in the field of
      transplantation medicine. BKV reactivation among renal-transplant recipients
      could cause BK associated nephropathy, which has unfavorable prognosis and is a
      cause for graft rejection. It is not clear why only few transplanted patients
      develop BK associated nephropathy while most exhibit asymptomatic viruria. One of
      the possible reasons lies in the mutations of the VP1 gene, encoding the main
      structural protein, bearing important determinants for the recognition of
      specific cellular receptors. The change of amino acid sequence could result in
      altered pathogenicity of BKV. The amplified sequences of BK in this research were
      from urines of patients with various clinical conditions along with healthy
      individuals. Nevertheless the sequence analysis which was undertaken did not show
      correlation between the viral genotype and the clinical condition. It was
      demonstrated that the most common BKV genotype in Bulgaria is genotype I and that
      the strains common in Bulgaria (genotypes I and IV) have typical European origin.
      Most of the sequenced BKV DNA samples (8/10) were correlated with the highest
      degree of similarity (81%) to the subcluster Ib. A specific place among the
      samples is taken by Pr-9, amplified from the urine of a pregnant woman that has a
      different evolutionary origins and might establish the beginning of a new
      distinct BKV strain.

PMID- 20029814
TI  - Prediction of response to treatment of chronic hepatitis B with pegylated
      interferon in the Philippines.
AB  - The response marker for interferon has not been investigated fully for hepatitis
      B viruses (HBVs) in the Philippines where novel subtypes B5 and C5 were
      recognized recently. The prediction parameters for interferon treatment were
      assessed, with emphasis on the mutation patterns in the basal core promoter and
      precore regions in patients with chronic hepatitis B. Seventeen HBeAg-positive
      patients were stratified according to response to treatment with pegylated
      interferon based on HBe seroconversion and HBV load. Intra-patient distributions
      of wild-type strains (A1762, G1764) and variants (T1762, A1764) were analyzed
      using HBV-DNA amplification and subsequent molecular cloning. The rate of
      variants (T1762, A1764) harbored by a patient was higher among responders (41.2%
      and 31% per person on average) than among non-responders (2.4% and 2.4%) to
      treatment with pegylated interferon at the baseline, respectively (P < 0.05). The
      rate of variants (T1762, A1764) harbored by responders (41.2% and 31%) decreased
      to 1.7% and 1.7%, and wild-type strains (A1762, G1764) conversely became majority
      (98.3% and 98.3%) after treatment with pegylated interferon, respectively. HBV
      strains harbored by two of six responders and a patient with lower baseline load
      (1.0 x 10(4) copies/ml) showed genotype shift from A to other genotypes, where
      genotype A disappeared preferentially after the loss of HBeAg and genotypes B and
      C formed a major population. These results suggest that the HBV variants (T1762,
      A1764) and HBV genotype A in the Philippines have an advantage in the response to
      pegylated interferon. These results warrant a large-scale examination for further
      precise prediction of the response to treatment with interferon.

PMID- 20029815
TI  - Emergence of new norovirus variants and genetic heterogeneity of noroviruses and
      sapoviruses in children admitted to hospital with diarrhea in Thailand.
AB  - Enteric caliciviruses, including noroviruses (NoVs) and sapoviruses (SaVs), are
      recognized as important etiologic agents of acute gastroenteritis with
      considerable genetic diversity. In this study, fecal specimens collected from 147
      infants and young children admitted to hospital with acute gastroenteritis in
      2005 in Chiang Mai, Thailand, were screened for NoVs and SaVs by reverse
      transcription-multiplex polymerase chain reaction (RT-multiplex PCR). Ten
      isolates (6.8%) belonged to NoV GII genogroup and five (3.4%) were positive for
      SaVs. GII/4 was the most predominant genotype of NoVs, followed by GII/15, GII/6,
      and GII/12. Surprisingly, NoVs GII/1, GII/2, GII/3, GII/7, and GII/16 genotypes,
      which were detected previously during the 2002-2004 survey, were not detected in
      2005. Conversely, NoVs GII/6, GII/12, and GII/15 appeared in 2005 but were not
      detected during the 2002-2004 survey. The only genotype found to be common, as
      the most predominant genotype, in both surveys was NoV GII/4. Similar findings
      were also observed for SaVs, that is, the GI/2 and GIV detected during 2002-2004
      were not detected in 2005, while GI/5 and GII/3 detected in 2005 were not
      detected previously during the 2002-2004 surveillance. In addition, comprehensive
      genetic evolutionary analysis of NoV GII/4 genotype demonstrated that the
      majority of GII/4 detected in this study (CMH002/05, CMH005/05, CMH042/05, and
      CMH083/05) were classified as new NoV variants and fell into subtype GII/4-d
      (Hunter'04-like cluster). Only one NoV GII/4 strain (CMH142/05) belonged to
      subtype GII/4-e. The data indicated heterogeneity and highly dynamic genotypic
      distribution of NoVs and SaVs circulating in children admitted to hospital with
      acute gastroenteritis in Chiang Mai, Thailand.

PMID- 20029816
TI  - HIV-1 reverse transcriptase drug-resistance mutations in chronically infected
      individuals receiving or naive to HAART in Cameroon.
AB  - The most common first-line, highly active anti-retroviral therapy (HAART)
      received by individuals infected with HIV-1 in Cameroon is the combination
      therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors
      (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in
      Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate,
      the reverse transcriptase (RT) viral sequences in patient plasma were analyzed
      for the presence of mutations that confer drug resistance. Forty-nine HIV-1
      positive individuals were randomly selected from those receiving care in HIV/AIDS
      outpatient clinics in the South-West and North-West Regions of Cameroon. Among
      the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46%
      (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among
      those with drug-resistance mutations, there was a median of 14 months from the
      start of HAART, versus 9 months for those without; no difference was observed in
      the average viral load (10,997 copies/ml vs. 8,056 copies/ml). In contrast, drug
      naive individuals had a significantly higher average viral load (27,929
      copies/ml) than those receiving HAART (9,527 copies/ml). Strikingly, among the 21
      drug-naive individuals, 24% harbored viruses with drug-resistance mutations,
      suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon.
      Given the high frequency of resistance mutations among those on first-line HAART,
      coupled with the high prevalence of HIV-1 variants with drug-resistance mutations
      among drug-naive individuals, this study emphasizes the need for extensive
      monitoring of resistance mutations and the introduction of a second-line HAART
      strategy in Cameroon.

PMID- 20029817
TI  - A nationwide survey of hepatitis E virus infection in the general population of
      Japan.
AB  - To investigate nationwide the prevalence of hepatitis E virus (HEV) infection in
      the general population of Japan, serum samples were collected from 22,027
      individuals (9,686 males and 12,341 females; age, mean +/- standard deviation:
      56.8 +/- 16.7 years; range: 20-108 years) who lived in 30 prefectures located in
      Hokkaido, mainland Honshu, Shikoku, and Kyushu of Japan and underwent health
      check-ups during 2002-2007, and were tested for the presence of IgG, IgM, and IgA
      classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA by nested
      RT-PCR. Overall, 1,167 individuals (5.3%) were positive for anti-HEV IgG,
      including 753 males (7.8%) and 414 females (3.4%), the difference being
      statistically significant (P < 0.0001). The prevalence of anti-HEV IgG generally
      increased with age and was significantly higher among individuals aged >or=50
      years than among those aged <50 years (6.6% vs. 2.7%, P < 0.0001). Although 13
      individuals with anti-HEV IgG also had anti-HEV IgM and/or anti-HEV IgA, none of
      them had detectable HEV RNA. The presence of HEV RNA was further tested in 50 or
      49-sample minipools of sera from the remaining 22,014 individuals, and three
      individuals without anti-HEV antibodies tested positive for HEV RNA. The HEV
      isolates obtained from the three viremic individuals segregated into genotype 3
      and were closest to Japan-indigenous HEV strains. When stratified by geographic
      region, the prevalence of anti-HEV IgG as well as the prevalence of HEV RNA or
      anti-HEV IgM and/or anti-HEV IgA was significantly higher in northern Japan than
      in southern Japan (6.7% vs. 3.2%, P < 0.0001; 0.11% vs. 0.01%, P = 0.0056;
      respectively).

PMID- 20029818
TI  - Molecular detection and characterization of noroviruses from children in
      Botswana.
AB  - Stool specimens were collected from 100 children in Botswana. RT-PCR analysis
      detected noroviruses (NoVs) in 24% of samples tested. Genogroup I and genogroup
      II strains were identified. There was no association between NoV detection and
      age or gender. This study is the first indication that NoVs circulate widely in
      Botswana.

PMID- 20029819
TI  - Occult hepatitis B infection in patients infected with HIV: report of two cases
      of hepatitis B reactivation and prevalence in a hospital cohort.
AB  - Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV) are particularly at risk of hepatitis B reactivation. Two cases of
      patients infected with HIV with isolated anti-HBc antibodies who had experienced
      an HBV reactivation are described. In the two cases HBV reactivation occurred
      after withdrawal of anti-retroviral treatment with anti-HBV activity from the
      patients' highly active antiretroviral therapy (HAART), in accordance with HIV
      genotypic resistance profiles. Consequently, plasma samples from 383 patients
      infected with HIV were tested to assess the prevalence of occult HBV infection in
      the Infectious Diseases Department Unit of Nancy Hospital by investigating
      serological patterns and HBV replication. Forty-five percent (172/383) of
      patients had had previous contact with HBV. Isolated anti-HBc antibodies were
      observed in 48 patients (48/383, 12%) and, among these, 2 were HBV-DNA positive.
      Since 75% (288/383) of the patients were treated with HAART, including at least
      one drug active against HBV, occult HBV infection was perhaps unrecognized. In
      cases of HIV infection, all patients should be screened for HBV infection and the
      knowledge of HBV status as well as the monitoring of HBV viral load are essential
      in preventing HBV reactivation. Consideration should be given to the continuation
      of drugs with anti-HBV activity in co-infected patients receiving HAART, as
      cessation of therapy is associated with a risk of HBV reactivation. At least,
      close monitoring of the HBV viral load is warranted in such situations.

PMID- 20029820
TI  - Ageism in first episode psychosis.
AB  - OBJECTIVE: To consider the characteristics of first episode psychosis in older
      adults in a county in North East England. METHOD/DESIGN: The present study used a
      naturalistic design to compare individuals aged 65 years and over with those
      under 65, with a first episode psychosis. Data were collected on demographics,
      diagnosis at presentation and hospital admissions in the first year. RESULTS:
      Almost a quarter of all patients were aged 65 years or older. The older group
      were admitted later on after presentation, but with longer average hospital stays
      (p < 0.01), compared to the younger group, with no difference in the use of the
      Mental Health Act. Late onset schizophrenia (40-59 years) and very late onset
      schizophrenia-like psychosis (60 + years) formed a considerable proportion of
      patients. CONCLUSIONS: There is a substantial proportion of older people with
      first episode psychosis, with a significant use of hospital bed days. There are
      large gaps in services for this group who often do not have the same access to
      those offered to younger people, e.g. Assertive Outreach or crisis teams, access
      to Clozapine and CBT. Ageism exists in all forms; the elderly are doubly
      disadvantaged in view of their age and mental illness.In view of the Age
      Discrimination Act (2006) the elderly functionally ill group of patients should
      be entitled to the same level of care and equal access to services as younger
      people. More attention and interventions need to be focused on this overlooked
      group.

PMID- 20029821
TI  - Does consumption of processed foods explain disparities in the body weight of
      individuals? The case of Guatemala.
AB  - Overweight/obesity, caused by the 'nutrition transition', is identified as one of
      the leading risk factors for non-communicable mortality. The nutrition transition
      in developing countries is associated with a major shift from the consumption of
      staple crops and whole grains to highly and partially processed foods. This study
      examines the contribution of processed foods consumption to the prevalence of
      overweight/obesity in Guatemala using generalized methods of moments (GMM)
      regression. The results show that all other things remaining constant, a 10%
      point increase in the share of partially processed foods from the total household
      food expenditure increases the BMI of family members (aged 10 years and above) by
      3.95%. The impact of highly processed foods is much stronger. A 10% point
      increase in the share of highly processed food items increases the BMI of
      individuals by 4.25%, ceteris paribus. The results are robust when body weight is
      measured by overweight/obesity indicators. These findings suggest that increasing
      shares of partially and highly processed foods from the total consumption
      expenditure could be one of the major risk factors for the high prevalence of
      overweight/obesity in the country.

PMID- 20029822
TI  - Women with advanced breast cancer and their spouses: diversity of support and
      psychological distress.
AB  - OBJECTIVE: The current study examines the effect of perceived support from
      different agents (spouse, family, friends, religion-spirituality) on
      psychological distress experienced by women with advanced breast cancer and their
      male spouses. METHODS: In all, 150 couples consisting of women with advanced
      breast cancer and their spouses completed the Cancer Perceived Agent of Support
      Questionnaire and the Brief Symptom Inventory Scale. RESULTS: Spouses reported
      more psychological distress (global, depression and anxiety) than patients. Both
      patients and spouses report a similar level of spousal support, and spouses
      reported a lower level of support provided from family and friends. Perceived
      support in the current study contributed significantly to the explanations of
      global psychological distress, depression and anxiety both for patients and their
      spouses. However, the specific agents of support that were significant in
      explaining these outcomes varied between patients and their spouses. For
      patients, family support received by both patient and partner was the most
      important source of support, protecting from psychological distress, while for
      the male partners, support from friends was most important. Religious-based
      support was found to contribute negatively to the psychological distress of the
      patient and spouse. CONCLUSIONS: This study emphasizes the role of breast cancer
      spouses as care receivers in parallel to their role as caregivers, which is
      especially important in light of the high psychological distress reported by the
      spouses. The findings support the buffering effect, which different agents of
      support have against psychological distress while facing cancer for both patients
      and spouses. Patients and spouses differ with regard to the agents of support
      possessing this buffering effect.

PMID- 20029824
TI  - Canadian Alzheimer's disease caregiver survey: baby-boomer caregivers and burden
      of care.
AB  - OBJECTIVE: Alzheimer's disease (AD) burdens not only the person, but also the
      person's caregiver(s). This burden has been linked to negative health effects for
      caregivers. To that end, a survey of Canadian caregivers of persons with AD/other
      dementias was conducted to investigate the social, physical, psychological and
      financial impact of AD and/or dementia-related conditions on caregivers' quality
      of life. METHODS: A web-based survey, the Canadian Alzheimer's Disease Caregiver
      survey, was made available through the Canadian Alzheimer's Society website and
      50plus.com, an internet portal for baby boomers (BB) (people aged 50 years or
      older), as well as through HarrisDecima Research's e-Vox panel. A total of 398
      individuals completed the survey between 15 September and 5 November 2006.
      RESULTS: Of the 398 total respondents, 221 were identified as baby boomers who
      provided care to an individual with AD/dementia. Respondents identified several
      areas of burden of care. These included negative effects on emotional health
      (such as increased depression, more stress and greater fatigue), financial costs
      and a need to change a working situation (e.g. by retiring early, reducing work
      hours or refusing a promotion). CONCLUSION: Caregivers of persons with AD/related
      dementia face important social, physical, psychological and financial pressures.
      These negatively affect the quality of life of caregivers with a significant
      increased burden being placed on live-in caregivers versus caregivers who do not
      co-reside with their care recipients. Interventions that address these pressures
      will not only improve the health and well-being of caregivers, but likely also
      the care of persons with AD/dementia.

PMID- 20029823
TI  - A computer case definition for sudden cardiac death.
AB  - PURPOSE: To facilitate studies of medications and sudden cardiac death, we
      developed and validated a computer case definition for these deaths. The study of
      community dwelling Tennessee Medicaid enrollees 30-74 years of age utilized a
      linked database with Medicaid inpatient/outpatient files, state death certificate
      files, and a state 'all-payers' hospital discharge file. METHODS: The
      computerized case definition was developed from a retrospective cohort study of
      sudden cardiac deaths occurring between 1990 and 1993. Medical records for 926
      potential cases had been adjudicated for this study to determine if they met the
      clinical definition for sudden cardiac death occurring in the community and were
      likely to be due to ventricular tachyarrhythmias. The computerized case
      definition included deaths with (1) no evidence of a terminal hospital
      admission/nursing home stay in any of the data sources; (2) an underlying cause
      of death code consistent with sudden cardiac death; and (3) no terminal
      procedures inconsistent with unresuscitated cardiac arrest. This definition was
      validated in an independent sample of 174 adjudicated deaths occurring between
      1994 and 2005. RESULTS: The positive predictive value of the computer case
      definition was 86.0% in the development sample and 86.8% in the validation
      sample. The positive predictive value did not vary materially for deaths coded
      according to the ICO-9 (1994-1998, positive predictive value = 85.1%) or ICD-10
      (1999-2005, 87.4%) systems. CONCLUSION: A computerized Medicaid database, linked
      with death certificate files and a state hospital discharge database, can be used
      for a computer case definition of sudden cardiac death.

PMID- 20029825
TI  - Efficient removal of unwanted signals in NMR spectra using the filter
      diagonalization method.
AB  - It is often desirable to selectively remove corrupting or uninteresting signals
      from complex NMR spectra without disturbing overlapping or nearby signals. For
      biofluids in particular, removal of solvent and urea signals is important for
      retaining quantitative accuracy in NMR-based metabonomics. This article presents
      a novel algorithm for efficient filtering of unwanted signals using the filter
      diagonalization method (FDM). Unwanted signals are modeled in the time domain
      using FDM. This modeled signal is subtracted from the original free induction
      decay. The resulting corrected signal is then processed using established
      workflow. The algorithm is found to be reliable and fast. By eliminating large,
      broad, uninteresting signals, many spectra can be subjected to fully automated
      absolute value processing, allowing objective preparation of spectra for pattern
      recognition analysis.

PMID- 20029826
TI  - Developmental competence of morphologically poor oocytes in relation to
      follicular size and oocyte diameter in the pig.
AB  - The objective of this study was to assess the practical usefulness of
      morphologically poor oocytes (MPCOCs) in relation to follicular size and oocyte
      diameter. Oocytes collected from medium (3-8 mm in diameter) and small (<3 mm)
      follicles were classified into five categories of morphologically good oocytes
      (MGCOCs) from medium follicles (MA, control), MPCOCs with larger and smaller
      diameters from medium follicles (ML and MS, respectively), and those from small
      follicles (SL and SS, respectively). The oocytes were examined for maturation and
      developmental competence after parthenogenesis and somatic cell nuclear transfer
      (SCNT). Nuclear maturation of ML oocytes (91%) was similar to that of control
      oocytes (94%), but higher than MS (80%), SL (79%), and SS (63%) oocytes. This
      pattern was also observed in the intracellular glutathione level, p34(cdc2)
      kinase activity, and gene (CDK1, PCNA, and ERK2) expression levels in in vitro
      matured oocytes. ML oocytes showed a similar proportion of blastocyst formation
      (20%) after SCNT to control oocytes (21%). In addition, the use of ML oocytes
      resulted in a 50% farrowing rate with 1.8% efficiency of piglet production after
      SCNT embryo transfer, while control oocytes showed a 60% farrowing rate with 2.4%
      production efficiency. Our results demonstrate that MPCOCs, if appropriately
      selected, have a comparable ability to MGCOCs in supporting not only in vitro
      blastocyst formation, but also development to term in vivo after SCNT. These
      oocytes can be used as a source for in vitro production of embryos with normal in
      vivo viability in pigs.

PMID- 20029827
TI  - Copy number and sequence variants implicate APBA2 as an autism candidate gene.
AB  - We recently reported an autistic proband and affected sibling with maternally
      inherited microduplications within the 15q13.1 and 15q13.3 regions that contain a
      total of 4 genes. The amyloid precursor protein-binding protein A2 (APBA2) gene
      is located within the 15q13.1 duplication and encodes a neuronal adaptor protein
      essential to synaptic transmission that interacts directly with NRXN1 at the
      presynaptic membrane. We interpreted this as evidence for a putative role of
      APBA2 in autism as larger maternal duplications of 15q11-q13 are the most common
      known cause of autism. We therefore resequenced 512 subjects with autism spectrum
      disorder (ASD) and 463 controls, and identified 7 novel nonsynonymous coding
      variants in ASD subjects compared with 4 in controls. Five of the seven variants
      in the ASD group were predicted to affect protein function, alter residues
      conserved across 18 species, or both. All of the variants for which parental DNA
      was available were inherited. We also found two different nonsynonymous variants
      in two siblings with autism: (1) a paternally inherited heterozygous 6 bp
      deletion and (2) a maternally inherited heterozygous missense mutation, the
      latter also found in a single control. These results indicate compound
      heterozygous mutations of APBA2 in this autism sibship. The co-occurrence of two
      nonsynonymous mutations in both affected siblings in a single family, each
      transmitted from a different unaffected parent, suggest a role for APBA2
      mutations in rare individuals with ASD.

PMID- 20029831
TI  - Role of dopamine D(1) receptors in caffeine-mediated ERK phosphorylation in the
      rat brain.
AB  - The aim of this research was to study the role of dopamine D(1) receptors in
      caffeine elicited ERK phosphorylation in the prefrontal and other cortical
      (cingulate and motor) and subcortical (shell and core of the nucleus accumbens)
      regions. To this end, caffeine (3 and 10 mg/kg) was administered before
      phosphoERK immunohistochemistry. Caffeine dose-dependently increased the number
      of phosphoERK-positive neurons in the prefrontal and cingulate cortices but not
      in the secondary motor cortex and in the nucleus accumbens shell and core. The
      dopamine D(1) receptor antagonist, SCH 39166 (50 microg/kg), fully prevented
      phosphoERK activation by caffeine (10 mg/kg) in the superficial and deep layers
      of the prefrontal cortex but failed to prevent it in the cingulate cortex. Given
      that phosphoERK can be regarded as a postsynaptic marker of neuronal activation,
      the present results indicate that psychotropic properties of caffeine may result
      from the activation of prefrontal, via dopamine D(1) receptors, and cingulate
      cortices. Failure of caffeine to activate ERK in the nucleus accumbens further
      supports, indirectly, the observation that caffeine fails to activate dopamine
      transmission in this structure and is consistent with the tenet that caffeine
      lacks of true addictive properties.

PMID- 20029832
TI  - Effects of the endogenous PPAR-alpha agonist, oleoylethanolamide on MDMA-induced
      cognitive deficits in mice.
AB  - MDMA (3,4-Methylenedioxymethamphetamine) is an amphetamine derivative widely used
      for recreational purposes. We have recently shown that repeated treatment with
      high doses of MDMA-induced impairments in the acquisition and recall of an active
      avoidance task in mice. In this study, we examined whether the endogenous
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist,
      oleoylethanolamide (OEA) protects against these MDMA-induced deficits. Mice were
      pretreated twice a day with OEA (0, 5, and 25 mg/kg) 30 min before an injection
      of MDMA (30 mg/kg) or saline during four consecutive days. Twenty-four hours
      after the last treatment, animals were trained in an active avoidance task for
      two consecutive weeks. After a 5-day resting period, a recall session was
      performed. Mice treated with MDMA showed reduced learning and recall of the task
      when compared with saline-treated controls. OEA at 5 mg/kg ameliorated and at 25
      mg/kg worsened this deficit. Dopamine transporter (DAT)-binding sites
      significantly decreased 4 days after the last MDMA administration and
      pretreatment with both doses of OEA prevented this effect. In immunohistochemical
      studies, coexpression of tyrosine-hydroxylase and PPAR-alpha receptors was
      observed in the striatum and substantia nigra pars compacta of mice. These
      results suggest that OEA administration can modulate the cognitive deficits
      induced by MDMA in a DAT-independent manner.

PMID- 20029829
TI  - Autism spectrum and obsessive-compulsive disorders: OC behaviors, phenotypes and
      genetics.
AB  - Autism spectrum disorders (ASDs) are a phenotypically and etiologically
      heterogeneous set of disorders that include obsessive-compulsive behaviors (OCB)
      that partially overlap with symptoms associated with obsessive-compulsive
      disorder (OCD). The OCB seen in ASD vary depending on the individual's mental and
      chronological age as well as the etiology of their ASD. Although progress has
      been made in the measurement of the OCB associated with ASD, more work is needed
      including the potential identification of heritable endophenotypes. Likewise,
      important progress toward the understanding of genetic influences in ASD has been
      made by greater refinement of relevant phenotypes using a broad range of study
      designs, including twin and family-genetic studies, parametric and nonparametric
      linkage analyses, as well as candidate gene studies and the study of rare genetic
      variants. These genetic analyses could lead to the refinement of the OCB
      phenotypes as larger samples are studied and specific associations are
      replicated. Like ASD, OCB are likely to prove to be multidimensional and
      polygenic. Some of the vulnerability genes may prove to be generalist genes
      influencing the phenotypic expression of both ASD and OCD while others will be
      specific to subcomponents of the ASD phenotype. In order to discover molecular
      and genetic mechanisms, collaborative approaches need to generate shared samples,
      resources, novel genomic technologies, as well as more refined phenotypes and
      innovative statistical approaches. There is a growing need to identify the range
      of molecular pathways involved in OCB related to ASD in order to develop novel
      treatment interventions.

PMID- 20029833
TI  - Striatal and extrastriatal dopamine release measured with PET and [(18)F]
      fallypride.
AB  - The amphetamine challenge, in which positron emission tomography (PET) or single
      photon emission computed tomography radioligand binding following administration
      of amphetamine is compared to baseline values, has been successfully used in a
      number of brain imaging studies as an indicator of dopaminergic function,
      particularly in the striatum. [(18)F] fallypride is the first PET radioligand
      that allows measurement of the effects of amphetamine on D2/D3 ligand binding in
      striatum and extra-striatal brain regions in a single scanning session following
      amphetamine. We scanned 15 healthy volunteer subjects with [(18)F] fallypride at
      baseline and following amphetamine (0.3 mg/kg) using arterial plasma input-based
      modeling as well as reference region methods. We found that amphetamine effect
      was robustly detected in ventral striatum, globus pallidus, and posterior
      putamen, and with slightly higher variability in other striatal subregions.
      However, the observed effect sizes in striatum were less than those observed in
      previous studies in our laboratory using [(11)C] raclopride. Robust effect was
      also detected in limbic extra-striatal regions (hippocampus, amygdala) and
      substantia nigra, but the signal-to-noise ratio was too low to allow accurate
      measurement in cortical regions. We conclude that [(18)F] fallypride is a
      suitable ligand for measuring amphetamine effect in striatum and limbic regions,
      but it is not suitable for measuring the effect in cortical regions and may not
      provide the most powerful way to measure the effect in striatum.

PMID- 20029835
TI  - Selective probing of a NADPH site controlled light-induced enzymatic catalysis.
AB  - Achieving molecular recognition of NADPH binding sites is a compelling strategy
      to control many redox biological processes. The NADPH sites recognize the
      ubiquitous NADPH cofactor via highly conserved binding interactions, despite
      differences in the regulation of the hydride transfer in redox active proteins.
      We recently developed a photoactive NADPH substitute, called nanotrigger NT
      synchronizing the initiation of enzymatic catalysis of the endothelial NO
      synthase (eNOS) with a laser pulse. Spatial and temporal control of enzymatic
      activity by such a designed light-driven activator would benefit from achieving
      molecular selectivity, i.e. activation of a single NADPH-mediated enzyme.In this
      work, we probe the ability of NT to discriminate between two NADPH sites with
      light. The selected NADPH sites belong to dihydrofolate reductase dihydrofolate
      reductase enzyme (DHFR) and endothelial NO-synthase (eNOS). Ultrafast kinetics
      showed that NT could not activate DHFR catalysis with a laser pulse in contrast
      with the observed trigger of eNOS catalysis leading to NO formation. Homology
      modelling, molecular dynamics simulations showed that NT discriminated between
      the two NADPH sites by different donor to acceptor distances and by local steric
      effects hindering light activation of DHFR catalysis. The data suggested that the
      narrow NADPH site required a tight fit of the nanotrigger at a suitable
      distance/angle to the electron acceptor for a specific activation of the
      catalysis. The ability of the nanotrigger to activate eNOS combined with a low
      reactivity in unfavourable NADPH sites makes NT a highly promising tool for
      targeting eNOS in endothelial cells with a laser pulse.

PMID- 20029834
TI  - Preweaning manganese exposure causes hyperactivity, disinhibition, and spatial
      learning and memory deficits associated with altered dopamine receptor and
      transporter levels.
AB  - Epidemiological studies in children have reported associations between elevated
      dietary manganese (Mn) exposure and neurobehavioral and neurocognitive deficits.
      To better understand the relationship between early Mn exposure and
      neurobehavioral deficits, we treated neonate rats with oral Mn doses of 0, 25, or
      50 mg Mn/kg/day over postnatal day (PND) 1-21, and evaluated behavioral
      performance using open arena (PND 23), elevated plus maze (PND 23), and 8-arm
      radial maze (PND 33-46) paradigms. Brain dopamine D1 and D2-like receptors, and
      dopamine transporter (DAT) densities were determined on PND 24, and blood and
      brain Mn levels were measured to coincide with behavioral testing (PND 24, PND
      36). Preweaning Mn exposure caused hyperactivity and behavioral disinhibition in
      the open arena, but no altered behavior in the elevated plus maze. Manganese
      exposed males committed significantly more reference and marginally more working
      errors in the radial arm maze compared to controls. Fewer Mn exposed males
      achieved the radial maze learning criterion, and they required more session days
      to reach it compared to controls. Manganese-exposed animals also exhibited a
      greater frequency of stereotypic response strategy in searching for the baited
      arms in the maze. These behavioral and learning deficits were associated with
      altered expression of the dopamine D1 and D2 receptors and the DAT in prefrontal
      cortex, nucleus accumbens, and dorsal striatum. These data corroborate
      epidemiological studies in children, and suggest that exposure to Mn during
      neurodevelopment significantly alters dopaminergic synaptic environments in brain
      nuclei that mediate control of executive function behaviors, such as reactivity
      and cognitive flexibility.

PMID- 20029836
TI  - A molecular dynamics study on binding recognition between several 4,5 and 4,6
      linked aminoglycosides with A-site RNA.
AB  - A molecular dynamics (MD) simulation has been performed for two sets of
      aminoglycoside antibiotics bound with an RNA duplex corresponding to the
      aminoacyl-tRNA decoding site of the 16S rRNA to characterize the energetics and
      dynamics of binding for several aminoglycosides. The binding free energy,
      essential dynamics and hydration analysis have been conducted to characterize the
      dynamics' properties associated with the binding recognition between each set of
      antibiotics and the RNA duplex. We have built several dynamic models with
      reasonable binding free energies showing good correlation with the experimental
      data. We have also conducted a hydration analysis on some long residency water
      molecules detected as W8 and W49 sites around the U1406 . U1495 pair and which
      are found to be important in binding recognition and in causing some apparent
      stretch variations of this pair during the dynamic studies. In addition, we also
      find that the hydration sites with long residence time identified between the
      ring III of two 4,6-linked antibiotics (tobramycin and kanamycin) and phosphate
      oxygen atoms of G1405/U1406 may be worthy of further exploration for rational
      drug design.

PMID- 20029837
TI  - An improved SUMmOn-based methodology for the identification of ubiquitin and
      ubiquitin-like protein conjugation sites identifies novel ubiquitin-like protein
      chain linkages.
AB  - Ubiquitin (Ub) and the ubiquitin-like proteins (Ubls) comprise a remarkable
      assortment of polypeptides that are covalently conjugated to target proteins (or
      other biomolecules) to modulate their intracellular localization, half-life,
      and/or activity. Identification of Ub/Ubl conjugation sites on a protein of
      interest can thus be extremely important for understanding how it is regulated.
      While MS has become a powerful tool for the study of many classes of PTMs, the
      identification of Ub/Ubl conjugation sites presents a number of unique
      challenges. Here, we present an improved Ub/Ubl conjugation site identification
      strategy, utilizing SUMmOn analysis and an additional protease (lysyl
      endopeptidase C), as a complement to standard approaches. As compared with
      standard trypsin proteolysis-database search protocols alone, the addition of
      SUMmOn analysis can (i) identify Ubl conjugation sites that are not detected by
      standard database searching methods, (ii) better preserve Ub/Ubl conjugate
      identity, and (iii) increase the number of identifications of Ub/Ubl
      modifications in lysine-rich protein regions. Using this methodology, we
      characterize for the first time a number of novel Ubl linkages and conjugation
      sites, including alternative yeast (K54) and mammalian small ubiquitin-related
      modifier (SUMO) chain (SUMO-2 K42, SUMO-3 K41) assemblies, as well as previously
      unreported NEDD8 chain (K27, K33, and K54) topologies.

PMID- 20029838
TI  - iTRAQ-based quantitative analysis of protein mixtures with large fold change and
      dynamic range.
AB  - Quantitation of changes in protein abundance is key to understanding the
      alterations that biological systems undergo and to discovering novel biomarkers.
      Currently, HPLC-MS/MS can be used to quantify changes in protein expression
      levels [Ong, S. E. and Mann, M., Nat. Chem. Biol. 2005, 1, 252-262].
      Nevertheless, quantitative analysis of protein mixtures by HPLC-MS/MS is still
      hampered by the wide range of protein expression levels, the high dynamic range
      of protein concentrations and the lack of reliable quantitation algorithms
      [D'Ascenzo, M., et al. Brief. Funct. Genomic. Proteomic. 2008, 7, 127-135; Lin,
      W. T., et al., J. Proteome Res. 2006, 5, 2328-2338; Matthiesen, R., et al. J.
      Proteome Res. 2005, 4, 2338-2347; Yu, C. Y., et al. Nucleic Acids Res. 2007, 35,
      W707-W712]. In this context, we describe two different samples (4-protmix and 8
      protmix) suitable for relative protein quantitation using iTRAQ. Using the 4
      protmix, relative protein changes of up to 24-fold were measured. The 8-protmix
      allowed the quantitation of the relative protein changes in a mixture of proteins
      within the range of two orders of magnitude in concentration and ten-fold
      differences in relative abundance. We propose that the two samples are suited to
      test the iTRAQ quantitative proteomic workflow. We analyzed the iTRAQ samples
      with a LTQ Orbitrap using "higher energy collision-induced dissociation"
      fragmentation [Olsen, J. V., et al., Nat. Methods 2007, 4, 709-712] and
      quantified with Proteome Discoverer v.1.1 (Thermo Fisher Scientific). We believe
      that the presented protein mixtures will be useful to assess the performance of
      the iTRAQ-based quantitation proteomic strategy in any laboratory.

PMID- 20029839
TI  - A proteome map of the pituitary melanotrope cell activated by black-background
      adaptation of Xenopus laevis.
AB  - Upon transfer of Xenopus laevis from a white to a black background, the
      melanotrope cells in the pituitary pars intermedia secrete alpha-melanocyte
      stimulating hormone, which stimulates dispersion of melanin pigment in skin
      melanophores. This adaptive behavior is under the control of neurotransmitters
      and neuropeptides of hypothalamic origin. The alpha-melanocyte-stimulating
      hormone-producing cells and their hypothalamic control system provide an
      interesting model to study proteins required for biosynthetic and secretory
      processes involved in peptide hormone production and for brain-pituitary
      signaling. We present a 2-D PAGE-based proteome map of melanotrope cells from
      black-adapted animals, identifying 204 different proteins by MS analysis.

PMID- 20029840
TI  - Unrestricted identification of modified proteins using MS/MS.
AB  - Proteins undergo PTM, which modulates their structure and regulates their
      function. Estimates of the PTM occurrence vary but it is safe to assume that
      there is an important gap between what is currently known and what remains to be
      discovered. The highest throughput and most comprehensive efforts to catalogue
      protein mixtures have so far been using MS-based shotgun proteomics. The standard
      approach to analyse MS/MS data is to use Peptide Fragment Fingerprinting tools
      such as Sequest, MASCOT or Phenyx. These tools commonly identify 5-30% of the
      spectra in an MS/MS data set while only a limited list of predefined protein
      modifications can be screened. An important part of the unidentified spectra is
      likely to be spectra of peptides carrying modifications not considered in the
      search. Bioinformatics for PTM discovery is an active area of research. In this
      review we focus on software solutions developed for unrestricted identification
      of modifications in MS/MS data, here referred to as open modification search
      tools. We give an overview of the conceptually different algorithmic solutions to
      evaluate the large number of candidate peptides per spectrum when accounting for
      modifications of unrestricted size and demonstrate the value of results of large
      scale open modification search studies. Efficient and easy-to-use tools for
      protein modification discovery should prove valuable in the quest for mapping the
      dynamics of proteomes.

PMID- 20029841
TI  - Caenorhabditis elegans proteomics comes of age.
AB  - Caenorhabditis elegans, a free-living soil nematode, is an ideal model system for
      studying various physiological problems relevant to human diseases. Despite its
      short history, C. elegans proteomics is receiving great attention in multiple
      research areas, including the genome annotation, major signaling pathways (e.g.
      TGF-beta and insulin/IGF-1 signaling), verification of RNA interference-mediated
      gene targeting, aging, disease models, as well as peptidomic analysis of
      neuropeptides involved in behavior and locomotion. For example, a proteome-wide
      profiling of developmental and aging processes not only provides basic
      information necessary for constructing a molecular network, but also identifies
      important target proteins for chemical modulation. Although C. elegans has a
      simple body system and neural circuitry, it exhibits very complicated functions
      ranging from feeding to locomotion. Investigation of these functions through
      proteomic analysis of various C. elegans neuropeptides, some of which are not
      found in the predicted genome sequence, would open a new field of peptidomics.
      Given the importance of nematode infection in plants and mammalian pathogenesis
      pathways, proteomics could be applied to investigate the molecular mechanisms
      underlying plant- or animal-nematode pathogenesis and to identify novel
      antinematodal drugs. Thus, C. elegans proteomics, in combination of other
      molecular, biological and genetic techniques, would provide a versatile new tool
      box for the systematic analysis of gene functions throughout the entire life
      cycle of this nematode.

PMID- 20029842
TI  - Analysis of the budding yeast pH 4-7 proteome in meiosis.
AB  - Meiosis, the developmental programme generating haploid gametes from diploid
      precursors, requires two cell divisions and many innovations. In budding yeast, a
      large number of genes are expressed exclusively during meiosis while others are
      repressed compared to vegetative growth. Microarray analysis has shown that gene
      expression during meiosis is highly regulated, and has been used to classify
      yeast genes according to meiotic temporal expression pattern. In this study, we
      have begun to investigate the kinetics of meiotic protein expression using a
      proteomics approach. 2-D DIGE was used to characterise the temporal protein
      expression patterns of the budding yeast pH 4-7 proteome in meiosis. More than
      1400 meiotic protein spots were visualised and at least 63 spots were temporally
      regulated during meiosis in a statistically significant manner. Gel spots with
      significant expression changes were excised and 26 unique proteins were
      identified using LC-MS/MS. The identified proteins could be classified into
      functional categories and the genes encoding a number of these were previously
      shown to be involved in yeast sporulation and meiosis. This data set was used to
      assemble the first differential 2-D PAGE map of budding yeast meiosis, which can
      be accessed through a web server. This work represents one of the first
      quantitative proteomic analyses of meiosis in yeast and will provide a valuable
      resource for future investigations.

PMID- 20029843
TI  - Adjuvant effects of ambient particulate matter monitored by proteomics of
      bronchoalveolar lavage fluid.
AB  - Ambient particulate matter (PM) from air pollution is associated with
      exacerbation of asthma. The immunological basis for the adjuvant effects of PM is
      still not well understood. The generation of ROS and the resulting oxidative
      stress has been identified as one of the major mechanisms. Using a new intranasal
      sensitization model in which ambient PM is used as an adjuvant to enhance
      allergic inflammation (Li et al., Environ. Health Perspect. 2009, 117, 1116
      1123), a proteomics approach was applied to study the adjuvant effects of ambient
      PM. The enhanced in vivo adjuvant effect of ultrafine particles correlates with a
      higher in vitro oxidant potential and a higher content of redox-cycling organic
      chemicals. Bronchoalveolar lavage fluid proteins from normal and sensitized mice
      were resolved by 2-DE, and identified by MS. Polymeric immunoglobulin receptor,
      complement C3, neutrophil gelatinase-associated lipocalin, chitinase 3-like
      protein 3, chitinase 3-like protein 4, and acidic mammalian chitinase
      demonstrated significantly enhanced up-regulation by UFP with a polycyclic
      aromatic hydrocarbon content and a higher oxidant potential. These proteins may
      be the important specific elements targeted by PM in air pollution through the
      ability to generate ROS in the immune system, and may be involved in allergen
      sensitization and asthma pathogenesis.

PMID- 20029844
TI  - Silk cocoon of Bombyx mori: proteins and posttranslational modifications--heavy
      phosphorylation and evidence for lysine-mediated cross links.
AB  - Although silk is used to produce textiles and serves as a valuable biomaterial in
      medicine, information on silk proteins of the cocoon is limited. Scanning
      electron microscopy was applied to morphologically characterise the sample and
      the solubility of cocoon in lithium thiocyanate and 2-DE was carried out with
      multi-enzyme in-gel digestion followed by MS identification of silk-peptides.
      High-sequence coverage of the silk cocoon proteins fibroin light and heavy chain,
      sericins and fibrohexamerins was revealed and PTMs as heavy phosphorylation of
      silk fibroin heavy chain; lysine hydroxylation and Lys->allysine formation have
      been observed providing evidence for lysine-mediated cross linking of silk as
      found in collagens, which has not been reported so far. Tyrosine oxidation
      verified the presence of di-tyrosine cross links. A high degree of sequence
      conflicts probably representing single-nucleotide polymorphisms was observed. PTM
      and sequence conflicts may be modulating structure and physicochemical properties
      of silk.

PMID- 20029845
TI  - On-line desorption of dried blood spots coupled to hydrophilic
      interaction/reversed-phase LC/MS/MS system for the simultaneous analysis of drugs
      and their polar metabolites.
AB  - An assay for the simultaneous analysis of pharmaceutical compounds and their
      metabolites from micro-whole blood samples (i.e. 5 microL) was developed using an
      on-line dried blood spot (on-line DBS) device coupled with hydrophilic
      interaction/reversed-phase (HILIC/RP) LC/MS/MS. Filter paper is directly
      integrated to the LC device using a homemade inox desorption cell. Without any
      sample pretreatment, analytes are desorbed from the paper towards an automated
      system of valves linking a zwitterionic-HILIC column to an RP C18 column. In the
      same run, the polar fraction is separated by the zwitterionic-HILIC column while
      the non-polar fraction is eluted on the RP C18. Both fractions are detected by IT
      MS operating in full scan mode for the survey scan and in product ion mode for
      the dependant scan using an ESI source. The procedure was evaluated by the
      simultaneous qualitative analysis of four probes and their relative phase I and
      II metabolites spiked in whole blood. In addition, the method was successfully
      applied to the in vivo monitoring of buprenorphine metabolism after the
      administration of an intraperitoneal injection of 30 mg/kg on adult female Wistar
      rat.

PMID- 20029846
TI  - Chiral stationary phases for separation of intermedine and lycopsamine
      enantiomers from Symphytum uplandicum.
AB  - Enantioseparation of the pyrrolizidine alkaloid isomers intermedine and
      lycopsamine, isolated from Symphytum uplandicum, is discussed. The separatory
      power of two immobilized carbohydrate-based chiral HPLC columns, Chiralpak IA and
      IC, in different chromatographic conditions is compared. The study demonstrated
      the importance of solvent and column selection while developing such chiral HPLC
      separation methods. The baseline HPLC separation of the two alkaloid isomers in
      preparatory scale is reported for the first time. The optimized separations were
      achieved on a Chiralpak IA column with mobile phases of ACN/methanol (80:20) and
      methanol/methyl-t-butyl ether (90:10), both containing 0.1% diethylamine.

PMID- 20029851
TI  - BaO clusters on MgO nanocubes: a quantitative analysis of optical-powder
      properties.
AB  - Uniformly sized and shaped nanoparticles are well suited for the quantitative
      characterization of optical-powder properties. For the first time, quantum yields
      related to photoluminescence emissions that originate from the photoexcitation of
      MgO nanocube corners and edges are measured. In addition, the surfaces of these
      nanoparticles are doped with submonolayer barium, which oxidizes during
      adsorption onto the MgO nanocrystal surfaces and transforms in O(2) atmosphere
      into BaO. UV-Vis diffuse reflectance and photoluminescence spectroscopy is
      employed to explore whether 10(-3) monolayer equivalents of these dopants affect
      the MgO specific optical properties. Surface-admixed BaO produces additional
      absorption and photoluminescence emission features but does not significantly
      affect those specific to MgO nanocubes. On this basis the number of optically
      active sites that can be sampled inside a powder of alkaline earth oxide
      nanoparticles using a standard spectrometer system is estimated.

PMID- 20029850
TI  - The effects of size, shape, and surface functional group of gold nanostructures
      on their adsorption and internalization by cells.

PMID- 20029852
TI  - Competing risks and time-dependent covariates.
AB  - Time-dependent covariates are frequently encountered in regression analysis for
      event history data and competing risks. They are often essential predictors,
      which cannot be substituted by time-fixed covariates. This study briefly recalls
      the different types of time-dependent covariates, as classified by Kalbfleisch
      and Prentice [The Statistical Analysis of Failure Time Data, Wiley, New York,
      2002] with the intent of clarifying their role and emphasizing the limitations in
      standard survival models and in the competing risks setting. If random (internal)
      time-dependent covariates are to be included in the modeling process, then it is
      still possible to estimate cause-specific hazards but prediction of the
      cumulative incidences and survival probabilities based on these is no longer
      feasible. This article aims at providing some possible strategies for dealing
      with these prediction problems. In a multi-state framework, a first approach uses
      internal covariates to define additional (intermediate) transient states in the
      competing risks model. Another approach is to apply the landmark analysis as
      described by van Houwelingen [Scandinavian Journal of Statistics 2007, 34, 70-85]
      in order to study cumulative incidences at different subintervals of the entire
      study period. The final strategy is to extend the competing risks model by
      considering all the possible combinations between internal covariate levels and
      cause-specific events as final states. In all of those proposals, it is possible
      to estimate the changes/differences of the cumulative risks associated with
      simple internal covariates. An illustrative example based on bone marrow
      transplant data is presented in order to compare the different methods.

PMID- 20029853
TI  - Synthetic alpha-helix mimetics as agonists and antagonists of islet amyloid
      polypeptide aggregation.

PMID- 20029854
TI  - ZrO(HPO(4))(1-x)(FMN)(x): quick and easy synthesis of a nanoscale luminescent
      biomarker.

PMID- 20029855
TI  - Temperature-induced spin-transition in a low-spin cobalt(II) semiquinonate
      complex.

PMID- 20029856
TI  - Labeling and glycosylation of peptides using click chemistry: a general approach
      to (18)F-glycopeptides as effective imaging probes for positron emission
      tomography.

PMID- 20029857
TI  - Catalytic asymmetric synthesis of substituted 3-hydroxy-2-oxindoles.

PMID- 20029858
TI  - Enantiodivergent organocascade reactions.

PMID- 20029859
TI  - Anodic phenol-arene cross-coupling reaction on boron-doped diamond electrodes.

PMID- 20029860
TI  - Asymmetric synthesis of chiral silacarboxylic acids and their ester derivatives.

PMID- 20029861
TI  - High-resolution single-turnover mapping reveals intraparticle diffusion
      limitation in Ti-MCM-41-catalyzed epoxidation.

PMID- 20029862
TI  - Total synthesis of celogentin C by stereoselective C-H activation.

PMID- 20029863
TI  - Asymmetric synthesis of chiral tetraphenylenes.

PMID- 20029864
TI  - Strong two-photon excited fluorescence and stimulated emission from an organic
      single crystal of an oligo(phenylene vinylene).

PMID- 20029865
TI  - Spectroscopic evidence for an enhanced anion-cation interaction from hydrogen
      bonding in pure imidazolium ionic liquids.

PMID- 20029866
TI  - Carbonyl imines from oxaziridines: generation and cycloaddition of N-O=C dipoles.

PMID- 20029867
TI  - Substrate-controlled asymmetric total synthesis and structure revision of (+)
      itomanallene A.

PMID- 20029868
TI  - Remote control of regio- and diastereoselectivity in the hydroformylation of
      bishomoallylic alcohols with catalytic amounts of a reversibly bound directing
      group.

PMID- 20029869
TI  - Halogen bonding: a supramolecular entry for assembling nanoparticles.

PMID- 20029870
TI  - Copper-catalyzed direct alkenylation of N-iminopyridinium ylides.

PMID- 20029871
TI  - Autonomic self-healing of hydrogel thin films.

PMID- 20029872
TI  - Rhodium and iridium aminoborane complexes: coordination chemistry of BN alkene
      analogues.

PMID- 20029880
TI  - Polarized absorption, spontaneous and stimulated blue light emission of J-type
      tetraphenylbutadiene monocrystals.
AB  - Blue amplified spontaneous emission at room temperature is demonstrated from the
      exposed face of the strongly emitting organic semiconductor 1,1,4,4-tetraphenyl
      1,3-butadiene in single crystal form. The symmetry of the crystal and calculation
      of lattice sums indicate the J-type organization of the molecular transition
      moments. The minimum in the lowest exciton dispersion branch, from which emission
      takes place, is found at the edge of the Brillouin zone leading to a dominant
      vibronic emission since the zero-phonon line is forbidden. The observed gain
      narrowed line is attributed to the vibronic replica which becomes amplified with
      increased pumping. The reported emission is along the normal to the exposed
      crystal face, important for the development of vertical cavity geometry lasers
      based on organic single crystals. The threshold excitation fluence of 400 microJ
      cm(-2) is comparable to other organic crystalline systems, even if the
      amplification path is much reduced as a consequence of the vertical geometry.
      Considering these relevant aspects, the optical characterization of this material
      is provided. The polarized absorption spectra are reported and the properties of
      the lowest-energy excitonic state investigated. Calculation of the electronic
      transitions for the isolated molecule, lattice sums for the transition at lowest
      energy, and the symmetry of the crystal allow attributing the largest face of the
      samples and the observed optical bands in the spectra. Polarized time-resolved
      spectra are also reported allowing to identify the intrinsic excitonic emission.

PMID- 20029881
TI  - Tuning adsorption via strain and vertical ligand effects.
AB  - We report on the structure and electrochemical adsorption properties of well
      defined pseudomorphic Pt mono- and multilayers on Ru(0001). These act as model
      surfaces for Pt(111) with slightly decreased affinity to adsorbed hydrogen
      (H(ad)) and hydroxyl (OH(ad)). In cyclic voltammograms, this is reflected in more
      negative/positive potential regions for the reversible adsorption of upd
      H(ad)/OH(ad), respectively, compared to Pt(111). For upd-H(ad), we show that the
      corresponding trends can be predicted with high accuracy by density functional
      theory (DFT). In particular, the upd-H(ad) onset regions can be precisely
      simulated using the H(ad) adsorption energies from DFT, the layer thickness
      distribution from STM, and the base voltammogram of Pt(111) as reference.

PMID- 20029882
TI  - Can copper(II) mediate Hoogsteen base-pairing in a left-handed DNA duplex? A
      pulse EPR study.
AB  - Pulse EPR spectroscopy is used to investigate possible structural features of the
      copper(II) ion coordinated to poly(dG-dC).poly(dG-dC) in a frozen aqueous
      solution, and the structural changes of the polynucleotide induced by the
      presence of the metal ion. Two different copper species were identified and their
      geometry explained by a molecular model. According to this model, one species is
      exclusively coordinated to a single guanine with the N7 nitrogen atom forming a
      coordinative bond with the copper. In the other species, a guanine and a cytosine
      form a ternary complex together with the copper ion. A copper crosslink between
      the N7 of guanine and N3 of cytosine is proposed as the most probable
      coordination site. Moreover, no evidence was found for an interaction of either
      copper species with a phosphate group or equatorial water molecules. In addition,
      circular dichroism (CD) spectroscopy showed that the DNA of the Cu(II)-poly(dG
      dC).poly(dG-dC) adducts resembles the left-handed Z-form. These results suggest
      that metal-mediated Hoogsteen base pairing, as previously proposed for a right
      handed DNA duplex, can also occur in a double-stranded left-handed DNA.

PMID- 20029883
TI  - The role of ion pairs in the second-order NLO response of 4-X-1-methylpiridinium
      salts.
AB  - A series of 4-X-1-methylpyridinium cationic nonlinear optical (NLO) chromophores
      (X = (E)-CH=CHC(6)H(5); (E)-CH=CHC(6)H(4)-4'-C(CH(3))(3); (E)-CH=CHC(6)H(4)-4'
      N(CH(3))(2); (E)-CH=CHC(6)H(4)-4'-N(C(4)H(9))(2); (E,E)-(CH=CH)(2)C(6)H(4)-4'
      N(CH(3))(2)) with various organic (CF(3)SO(3)(-), p-CH(3)C(6)H(4)SO(3)(-)),
      inorganic (I(-), ClO(4)(-), SCN(-), [Hg(2)I(6)](2-)) and organometallic (cis
      [Ir(CO)(2)I(2)](-)) counter anions are studied with the aim of investigating the
      role of ion pairing and of ionic dissociation or aggregation of ion pairs in
      controlling their second-order NLO response in anhydrous chloroform solution. The
      combined use of electronic absorption spectra, conductimetric measurements and
      pulsed field gradient spin echo (PGSE) NMR experiments show that the second-order
      NLO response, investigated by the electric-field-induced second harmonic
      generation (EFISH) technique, of the salts of the cationic NLO chromophores
      strongly depends upon the nature of the counter anion and concentration. The ion
      pairs are the major species at concentration around 10(-3) M, and their dipole
      moments were determined. Generally, below 5x10(-4) M, ion pairs start to
      dissociate into ions with parallel increase of the second-order NLO response, due
      to the increased concentration of purely cationic NLO chromophores with improved
      NLO response. At concentration higher than 10(-3) M, some multipolar aggregates,
      probably of H type, are formed, with parallel slight decrease of the second-order
      NLO response. Ion pairing is dependent upon the nature of the counter anion and
      on the electronic structure of the cationic NLO chromophore. It is very strong
      for the thiocyanate anion in particular and, albeit to a lesser extent, for the
      sulfonated anions. The latter show increased tendency to self-aggregate.

PMID- 20029884
TI  - Excited-state dynamics of metal string complex Ni3(dpa)4X2 from femtosecond
      transient absorption spectra.
AB  - The excited-state dynamics of Ni(3)(dpa)(4)X(2), in which dpa is the ligand di(2
      pyridyl)amido and X = NCS or Cl, are investigated by transient absorption
      spectroscopy. The pi pi* and dd states are excited upon irradiation at
      wavelengths of 330 and 600 nm, respectively. Similar transient spectra are
      observed under the experimental temporal resolution. The transient species also
      show weak absorption. It is proposed that a low-lying metal-centered dd state is
      accessed immediately after excitation. Analyses of the experimental kinetic
      traces reveal a rapid conversion from a ligand-centered pi pi* state to a metal
      centered dd state in 0.1-0.4 ps. Vibrational cooling occurs with a time
      coefficient of 3.0-15.9 ps. From the spectral shift observed in the transient
      spectra relative to the steady-state spectra, the dd state is assigned as
      B(1)/B(2)(Ni(t)). This dd state eventually converts to the electronic ground
      state, in about 100 ps for the isothiocyanate complex and 200 ps for the
      chloride. In this trimetal string complex, relaxation to the ground electronic
      surface after excitation is therefore rapid.

PMID- 20029885
TI  - Controlled interfacial assembly and transfer of brushlike copolymer films.
AB  - The self-assembly and compression of polybutadiene-bpoly(ethylene oxide) (PBd
      PEO) at the air/water interface enables control over surface density, height, and
      film structure. Interfacial transfer was performed by a combination of Langmuir
      Blodgett (LB) and Langmuir-Schaefer (LS) techniques, resulting in monolayer and
      bilayer films. Ellipsometry and wettability results were used to characterize the
      efficiency of transfer and to determine the properties of the resulting films,
      confirming a brushlike monolayer. Importantly, a high surface density is
      essential to obtain the desired film structure (i.e. a dense brush) and surface
      properties. The films were challenged by adsorption of fibrinogen, and the
      results are consistent with the notion of a PEO-enriched, and protein-repellant,
      bilayer surface. Such a bilayer film provides an opportunity for a tunable
      biomaterial interface to probe cell-surface interactions.

PMID- 20029886
TI  - Self-diffusion on Au(100): a density functional theory study.
AB  - We used density functional theory to detail new self-diffusion mechanisms on
      perfect and imperfect Au(100) surfaces. Herein, we report binding energies of
      stable intermediates and transition states lying on the potential energy surface
      for these systems. We report migration pathways in the presence of a variety of
      surface defects and along different step edges, explaining their energetics in
      terms of chemical bonding. Furthermore, diffusion rate constants are deduced,
      which are useful for both experimental verification and for implementation into
      large-scale kinetic Monte Carlo simulations.

PMID- 20029887
TI  - An efficient and convenient synthesis of ethyl 1-(4-methoxyphenyl)-5-phenyl-1H
      1,2,3-triazole-4-carboxylate.
AB  - The "click chemistry" of using organic azides and terminal alkynes is arguably
      the most efficient and straightforward route to the synthesis of 1,2,3-triazoles.
      In this paper, an alternative and direct access to ethyl 1-(4-methoxyphenyl)-5
      phenyl-1H-1,2,3-triazole-4-carboxylate is described. Treatment of ethyl
      diazoacetate with 4-methoxyaniline derived aryl imines in the presence of 1,8
      diazabicyclo[5.4.0]undec-7-ene provided fully substituted 1,2,3-triazoles in good
      to high chemical yields. The base-mediated reaction tolerates various substituted
      phenyl imines as well as ethyl diazoacetate or the more bulky diazoacetamide. A
      reasonable mechanism is proposed that involves the addition of an imine nitrogen
      atom to the terminal nitrogen atom of the diazo compound, followed by
      aromatization to give the 1,2,3-triazole. The presence of the 4-carboxy group is
      advantageous as it can be easily transformed into other functional groups.

PMID- 20029888
TI  - Functionalized carbon nanomaterials derived from carbohydrates.
AB  - A tremendous growth in the field of carbon nanomaterials has led to the emergence
      of carbon nanotubes, fullerenes, mesoporous carbon and more recently graphene.
      Some of these materials have found applications in electronics, sensors,
      catalysis, drug delivery, composites, and so forth. The high temperatures and
      hydrocarbon precursors involved in their synthesis usually yield highly inert
      graphitic surfaces. As some of the applications require functionalization of
      their inert graphitic surface with groups like -COOH, -OH, and -NH(2), treatment
      of these materials in oxidizing agents and concentrated acids become inevitable.
      More recent works have involved using precursors like carbohydrates to produce
      carbon nanostructures rich in functional groups in a single-step under
      hydrothermal conditions. These carbon nanostructures have already found many
      applications in composites, drug delivery, materials synthesis, and Li ion
      batteries. The review aims to highlight some of the recent developments in the
      application of carbohydrate derived carbon nanostructures and also provide an
      outlook of their future prospects.

PMID- 20029889
TI  - Vesicle formation from an amphiphilic porphyrin derivative at the air-water
      interface.
AB  - A tetraphenyl porphyrin derivative with two C(16) alkyl chains covalently bound
      to each of the four peripheral phenyl rings through ether linkages formed
      multilayer clusters or vesicles at the air-water surface. More interestingly,
      spherical vesicles were also formed when deposited on appropriate solid surfaces,
      and these vesicles were stable even in dry conditions. Various microscopic images
      of the cast film deposited on a mica surface confirmed closed-ended
      nanotube/nanorod-type formation with necking and bulging. These narrow tubes are
      proposed to be intermediates for the formation of vesicles by fission at either
      side of the bulge. Such vesicular formation is not common when either cast or
      Langmuir-Blodgett films were deposited on a solid surface.

PMID- 20029890
TI  - Conformational polymorph of o-aminoanilinium(dibenzo[18]crown-6) supramolecules
      in [Ni(dmit)2]- salts.
AB  - The supramolecular (HOPD(+))(DB[18]crown-6) cation, in which HOPD(+) and
      DB[18]crown-6 are o-aminoanilinium and dibenzo[18]crown-6, respectively, was
      introduced into [Ni(dmit)(2)](-) salts (dmit(2-) = 2-thioxo-1,3-dithiole-4,5
      dithiolate). Conformational polymorphs were observed as tetragonal
      (HOPD(+))(DB[18]crown-6)[Ni(dmit)(2)](-) (1) and monoclinic (HOPD(+))(DB[18]crown
      6)[Ni(dmit)(2)](-) (2). The ammonium group of HOPD(+) in salts 1 and 2 formed the
      N-H(+)O hydrogen bonds at the bottom and upper positions of V-shaped DB[18]crown
      6, respectively, thereby producing a different supramolecular conformation. The
      [Ni(dmit)(2)](-) anion arrangements in salts 1 and 2 were 4(1)-helical pi
      stacking and a two-dimensional layer, respectively, depending on the conformation
      of the supramolecular cations. The magnetic behavior of salts 1 and 2 obeyed the
      Curie-Weiss law at room temperature with S = 1/2 spin on the [Ni(dmit)(2)](-)
      anion. However, the g value and line width in the electron resonance spectra of
      salt 1 showed a magnetic anomaly at 28 K, which was owing to antiferromagnetic
      ordering in the 4(1)-helical [Ni(dmit)(2)](-) pi stack. Large temperature- and
      frequency-dependent dielectric responses were observed for salt 2 at temperatures
      above 200 K, whereas no particular dielectric responses were observed in salt 1.
      The molecular motion of HOPD(+) within the cationic layer of salt 2 contributed
      to the dielectric response, and this was supported by ab initio calculations
      showing the potential-energy curve for pendulum motion and by the large thermal
      parameters in the X-ray crystal structure analysis. The fixed
      (HOPD(+))(DB[18]crown-6) arrangement in the crystal of salt 1 was consistent with
      the small dielectric response. The steric hindrance of the o-amino group of
      HOPD(+) in the supramolecular cation structure yielded the conformational
      polymorph with different dielectric and magnetic properties.

PMID- 20029891
TI  - Synthesis and rearrangement of stable NHC-->silylene adducts and their unique
      reactivity towards cyclohexylisocyanide.
AB  - The syntheses and reactivity of the two N-heterocyclic carbene (NHC) --> silylene
      complexes 2 and 4 have been investigated. The latter are easily accessible by
      reaction of the zwitterionic, N-heterocyclic silylene LSi: 1 [L=Ar-N
      C(=CH(2))CH=C(Me)-N-Ar, Ar=2,6-iPr(2)C(6)H(3)] with 1,3,4,5-tetramethylimidazol-2
      ylidene and 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene, respectively. While
      compound 2 undergoes facile rearrangement above -20 degrees C to give the
      unsymmetrical N-heterocyclic silylcarbene 3, the derivative 4 remains unchanged
      even after boiling in benzene. The remarkable reactivity of 3 and 4 towards
      cyclohexylisocyanide has been examined which leads in a unique series of C-H, Si
      H, and C-N bond activations to the new triaminosilanes 5 and 6, respectively. The
      novel compounds 3, 4, 5, and 6 were fully characterized by (1)H, (13)C, and
      (29)Si NMR spectroscopy, EI-MS, elemental analysis, and single-crystal X-ray
      diffraction.

PMID- 20029892
TI  - Controllable synthesis and optical properties of connected zinc oxide
      nanoparticles.
AB  - Connected zinc oxide (ZnO) nanoparticles are successfully synthesized by a simple
      solution-based chemical route that uses evaporation and concentration technology.
      The influences of processing parameters, especially the evaporation and
      concentration time on the size and morphology of the nanoparticles, have been
      investigated by transmission electron microscopy (TEM) and high-resolution TEM
      (HRTEM). The structure and optical properties are systematically characterized by
      X-ray diffraction (XRD), UV/Vis spectrophotometery, and fluorescence spectroscopy
      (FL). It is found that the average diameter and morphology are strongly affected
      by the evaporation and concentration time. Additionally, the formation mechanism
      of the nanoparticles is also discussed. The studies revealed that the evaporation
      and concentration are important aggregation or nucleation processes for ZnO
      growth, which leads to the macro-differences in morphology. These results provide
      some insight into the growth mechanism of ZnO nanostructures. The synthetic
      strategy developed in this study may also be extended to the preparation of other
      nanomaterials and promising applications in various fields of nanotechnology.

PMID- 20029894
TI  - An accelerated failure time mixture cure model with masked event.
AB  - We extend the Dahlberg and Wang (Biometrics 2007, 63, 1237-1244) proportional
      hazards (PH) cure model for the analysis of time-to-event data that is subject to
      a cure rate with masked event to a setting where the PH assumption does not hold.
      Assuming an accelerated failure time (AFT) model with unspecified error
      distribution for the time to the event of interest, we propose rank-based
      estimating equations for the model parameters and use a generalization of the EM
      algorithm for parameter estimation. Applying our proposed AFT model to the same
      motivating breast cancer dataset as Dahlberg and Wang (Biometrics 2007, 63, 1237
      1244), our results are more intuitive for the treatment arm in which the PH
      assumption may be violated. We also conduct a simulation study to evaluate the
      performance of the proposed method.

PMID- 20029895
TI  - Pattern-mixture zero-inflated mixed models for longitudinal unbalanced count data
      with excessive zeros.
AB  - Analysis of longitudinal data with excessive zeros has gained increasing
      attention in recent years; however, current approaches to the analysis of
      longitudinal data with excessive zeros have primarily focused on balanced data.
      Dropouts are common in longitudinal studies; therefore, the analysis of the
      resulting unbalanced data is complicated by the missing mechanism. Our study is
      motivated by the analysis of longitudinal skin cancer count data presented by
      Greenberg, Baron, Stukel, Stevens, Mandel, Spencer, Elias, Lowe, Nierenberg,
      Bayrd, Vance, Freeman, Clendenning, Kwan, and the Skin Cancer Prevention Study
      Group[New England Journal of Medicine 323, 789-795]. The data consist of a large
      number of zero responses (83% of the observations) as well as a substantial
      amount of dropout (about 52% of the observations). To account for both excessive
      zeros and dropout patterns, we propose a pattern-mixture zero-inflated model with
      compound Poisson random effects for the unbalanced longitudinal skin cancer data.
      We also incorporate an autoregressive of order 1 correlation structure in the
      model to capture longitudinal correlation of the count responses. A quasi
      likelihood approach has been developed in the estimation of our model. We
      illustrated the method with analysis of the longitudinal skin cancer data.

PMID- 20029896
TI  - Resampling in multiple-dose factorial designs.
AB  - Multiple-dose factorial designs may provide confirmatory evidence that (fixed)
      combination drugs are superior to either component drug alone. Moreover, a useful
      and safe range of dose combinations may be identified. In our study, we focus on
      (A) adjustments of the overall significance level made necessary by multiple
      testing, (B) improvement of conventional statistical methods with respect to
      power, distributional assumptions and dimensionality, and (C) construction of
      corresponding simultaneous confidence intervals. We propose novel resampling
      algorithms, which in a simple way take the correlation of multiple test
      statistics into account, thus improving power. Moreover, these algorithms can
      easily be extended to combinations of more than two component drugs and binary
      outcome data. Published data summaries from a blood pressure reduction trial are
      analysed and presented as a worked example. An implementation of the proposed
      methods is available online as an R package.

PMID- 20029897
TI  - Additive-multiplicative regression models for spatio-temporal epidemics.
AB  - An extension of the stochastic susceptible-infectious-recovered (SIR) model is
      proposed in order to accommodate a regression context for modelling infectious
      disease data. The proposal is based on a multivariate counting process specified
      by conditional intensities, which contain an additive epidemic component and a
      multiplicative endemic component. This allows the analysis of endemic infectious
      diseases by quantifying risk factors for infection by external sources in
      addition to infective contacts. Inference can be performed by considering the
      full likelihood of the stochastic process with additional parameter restrictions
      to ensure non-negative conditional intensities. Simulation from the model can be
      performed by Ogata's modified thinning algorithm. As an illustrative example, we
      analyse data provided by the Federal Research Centre for Virus Diseases of
      Animals, Wusterhausen, Germany, on the incidence of the classical swine fever
      virus in Germany during 1993-2004.

PMID- 20029898
TI  - Exploring spatial and multitype assemblages of species abundances.
AB  - The ecological theory of the existence of multiple stable states between species,
      or the spatial heterogeneity of some unobserved environmental factor, supports
      the idea of multitype interactions between species. These multitype interactions
      can lead to different assemblages of species abundances. An exploratory tool for
      the detection of these species assemblages and for their spatial analysis is
      presented in this article. A two-stage analysis is proposed. First, a
      classification into types of species assemblages using only the species
      abundances at each site, regardless of their spatial location, is performed. The
      clustering procedure is based on multivariate normal mixtures and provides a
      measure of the classification uncertainty. Second, some tools for the study of
      the spatial structure of these types of assemblages are presented. We transfer
      the classification uncertainty to the spatial analysis of the classes in order to
      draw more accurate conclusions. This classification and spatial analysis method
      is used to point out a spatial gradient of infection in a host-pathogen system in
      the Aland Islands in Finland. It can be a useful preliminary tool for ecological
      studies involving the spatial distributions of several species.

PMID- 20029899
TI  - Interval estimation of the effective population size from heterozygote-excess in
      SNP markers.
AB  - The effective population size N(e) is an important parameter in population
      genetics and conservation biology. In recent years, there has been great interest
      in the use of molecular markers to estimate N(e). Although the point estimates
      from molecular markers in general suffer from a low reliability, the use of
      single nucleotide polymorphism (SNP) markers over a wide range of genome is
      expected to remarkably improve the reliability. In this study, expressions were
      derived for interval estimates of N(e) from one published method, the
      heterozygote-excess method, when it is applied to SNP markers. The conditional
      variance theory is applied to the derivation of a confidence interval for N(e)
      under random union of gametes, monogamy and polygyny. Stochastic simulation shows
      that the obtained confidence interval is slightly conservative, but fairly useful
      for practical applications. The result is illustrated with real data on SNP
      markers in a pig strain.

PMID- 20029903
TI  - Biophotonics for dermatology: science & applications.

PMID- 20029904
TI  - Food analysis.

PMID- 20029905
TI  - Analytical food control does not live up to expectations--what to do?
AB  - There are good reasons to devote a special issue to food analysis. First of all
      it is a challenging field, extremely wide and complex. There is a need for many
      more methods and plenty of room for technical improvements, as will be shown in
      the articles presented in this issue. However, there are also structural problems
      to be discussed, which are as challenging as the technical issues. Analytical
      chemistry is primarily a tool and its development is directly linked to the
      success of the service it provides and the reputation it has. We analysts must,
      therefore, have an interest in the success of the tool we are developing,
      structural aspects of our profession, financial issues and perhaps even
      "politics".

PMID- 20029906
TI  - Identification, quantitation, and method validation for flavan-3-ols in fermented
      ready-to-drink teas from the Italian market using HPLC-UV/DAD and LC-MS/MS.
AB  - The present study is focused on flavan-3-ols characterizing the antioxidant
      properties of fermented tea (Camellia sinensis). These bioactive compounds,
      object of nutritional claims in commercial products, should be quantified with
      rigorous analytical procedures whose accuracy and precision have been stated with
      a certain level of confidence. An HPLC-UV/DAD method, able to detect and quantify
      flavan-3-ols in infusions and ready-to-drink teas, has been developed for routine
      analysis and validated by characterizing several performance parameters. The
      accuracy assessment has been run through a series of LC-MS/MS analyses.
      Epigallocatechin, (+)-catechin, (-)-epigallocatechingallate, (-)-epicatechin, (-)
      gallocatechingallate, (-)-epicatechingallate, and (-)-catechingallate were chosen
      as markers of the polyphenolic fraction. Quantitative results showed that samples
      obtained from tea leaves infusion were richer in polyphenolic antioxidants than
      those obtained through other industrial processes. The influence of shelf-life
      and packaging material on the flavan-3-ols content was also considered; markers
      decreased, with an exponential trend, as a function of time within the shelf life
      while packaging materials demonstrated to influence differently the flavan-3-ol
      fraction composition over time. The method presented here provides quantitative
      results with a certain level of confidence and is suitable for a routine quality
      control of iced teas whose antioxidant properties are object of nutritional
      claim.

PMID- 20029907
TI  - Coumarins and phenolic fingerprints of oak and Brazilian woods extracted by
      sugarcane spirit.
AB  - A total of 25 sugarcane spirit extracts of six different Brazilian woods and oak,
      commonly used by cooperage industries for aging cachaca, were analyzed for the
      presence of 14 phenolic compounds (ellagic acid, gallic acid, vanillin,
      syringaldehyde, synapaldehyde, coniferaldehyde, vanillic acid, syringic acid,
      quercetin, trans-resveratrol, catechin, epicatechin, eugenol, and myricetin) and
      two coumarins (scopoletin and coumarin) by HPLC-DAD-fluorescence and HPLC-ESI
      MS(n). Furthermore, an HPLC-DAD chromatographic fingerprint was build-up using
      chemometric analysis based on the chromatographic elution profiles of the
      extracts monitored at 280 nm. Major components identified and quantified in
      Brazilian wood extracts were coumarin, ellagic acid, and catechin, whereas oak
      extracts shown a major contribution of catechin, vanillic acid, and
      syringaldehyde. The main difference observed among oak and Brazilian woods
      remains in the concentration of coumarin, catechin, syringaldehyde, and
      coniferaldehyde. The chemometric analysis of the quantitative profile of the 14
      phenolic compounds and two coumarins in the wood extracts provides a
      differentiation between the Brazilian wood and oak extracts. The chromatographic
      fingerprint treated by multivariate analysis revealed significant differences
      among Brazilian woods themselves and oak, clearly defining six groups of wood
      extracts: (i) oak extracts, (ii) jatoba extracts, (iii) cabreuva-parda extracts,
      (iv) amendoim extracts, (v) canela-sassafras extracts and (vi) pequi extracts.

PMID- 20029908
TI  - Varietal characterization of hop (Humulus lupulus L.) by GC-MS analysis of hop
      cone extracts.
AB  - An approach is described for use in the varietal characterization of hop (Humulus
      lupulus L.) varieties. The study focuses on commercial hop varieties and was
      timed to coincide with the 2008 commercial hop harvest in Tasmania, Australia.
      Analysis of hop extracts was performed using GC-MS. A 60 m capillary column was
      employed to increase efficiency to permit the use of a quadrupole mass
      spectrometer in place of a time of flight mass spectrometer that is more commonly
      used for this type of analysis. A set of characterization functions were derived
      from discriminant analysis which were highly suitable for varietal
      characterization of the eight commercial varieties included in the study, namely
      Willamette, Victoria, Pride of Ringwood, Cascade, Southern Hallertau, Millennium,
      Southern Saaz, and Super Pride.

PMID- 20029909
TI  - Headspace solid-phase microextraction for direct determination of volatile
      phenols in cider.
AB  - A headspace solid-phase microextraction coupled to gas chromatography-tandem mass
      spectrometry (GC-MS/MS) method was optimised and validated for the determination
      of 4-ethylguaiacol, 4-ethylphenol, 4-vinylguaiacol and 4-vinylphenol, involved in
      the presence of Brett character, in ciders. The influence of different parameters
      on extraction efficiency (fibre coating, salt addition, exposure time, extraction
      temperature and sample volume/total volume ratio) was evaluated.
      Divinylbenzene/carboxen/PDMS was selected as extraction fibre and the other
      optimised parameters were as follows: 10 mL of cider, temperature 70 degrees C,
      extraction time 60 min and addition of 0.4 g/mL of NaCl. The proposed method
      showed satisfactory linearity. The detection limits obtained were 0.01 microg/L
      for 4-ethylguaiacol, 0.02 microg/L for 4-ethylphenol, 0.08 microg/L for 4
      vinylguaiacol and 0.03 microg/L for 4-vinylphenol. These detection limits were
      lower than those obtained in previous studies on the determination of volatile
      phenols in other alcoholic beverages. Good recoveries of over 95% were observed
      for all compounds, and the repeatability obtained was considered acceptable,
      ranging between 4 and 10%. To demonstrate the feasibility of the procedure, the
      method was applied to the analysis of commercial ciders. To our knowledge, this
      is the first time that the headspace solid-phase microextraction procedure has
      been optimised to determine specifically the Brett character responsible
      compounds in cider.

PMID- 20029912
TI  - Mental health parity legislation, cost-sharing and substance-abuse treatment
      admissions.
AB  - Treatment is highly cost-effective in reducing an individual's substance abuse
      (SA) and associated harms. However, data from Treatment Episodes (TEDS) indicate
      that per capita treatment admissions substantially lagged behind increases in
      heavy drug use from 1992 to 2007. Only 10% of individuals with clinical SA
      disorders receive treatment, and almost half who forgo treatment point to
      accessibility and cost constraints as barriers to care. This study investigates
      the impact of state mental health and SA parity legislation on treatment
      admission flows and cost-sharing. Fixed effects specifications indicate that
      mandating comprehensive parity for mental health and SA disorders raises the
      probability that a treatment admission is privately insured, lowering costs for
      the individual. Despite some crowd-out of charity care for private insurance,
      mandates reduce the uninsured probability by a net 2.4 percentage points. States
      mandating comprehensive parity also see an increase in treatment admissions.
      Thus, increasing cost-sharing and reducing financial barriers may aid the at-risk
      population in obtaining adequate SA treatment. Supply constraints mute effect
      sizes, suggesting that demand-focused interventions need to be complemented with
      policies supporting treatment providers. These results have implications for the
      effectiveness of the 2008 Federal Mental Health Parity and Addiction Equity Act
      in increasing SA treatment admissions and promoting cost-sharing.

PMID- 20029913
TI  - Co-crystals with acetylene: small is not simple!
AB  - Acetylene is an amazingly versatile component for the formation of co-crystals.
      It requires careful handling and special techniques for crystallisation, but the
      efforts seem to be rewarding when attaining co-crystals with small molecules as
      partners. Many basic questions such as the dominance of specific heterogeneous
      intermolecular interactions, their driving force for the formation of
      multicomponent crystals instead of neat ones are expected to be easily analysed.
      The underlying packing patterns and resulting stoichiometries based on the known
      supramolecular synthons seem to be straightforward for such small molecules and
      crystal engineering, considered as the prototype of supramolecular synthesis,
      should be a simple task. Nineteen co-crystals with acetylene are presented in
      this paper, some of which have been previously reported individually. An attempt
      has been made to find features shared by the groups of co-crystals, including
      those that could not be co-crystallised. But in spite of clear ideas and
      experiences from previous experiments, surprisingly almost none of systems
      reached our expectations. Our intuitive approach was not fulfilled, which
      demonstrates that multicomponent crystals even of small molecules will remain a
      great challenge for theoretical methods and the crystal structures shown herein
      represent good candidates for future testing. On the other hand, we wish to
      encourage other groups to present their views on the crystal structures with an
      unbiased approach that may offer a better explanation than we are able to outline
      in this article.

PMID- 20029914
TI  - Thermal- and light-induced spin crossover in a guest-dependent dinuclear iron(II)
      system.
AB  - We previously reported the dinuclear material [Fe(II) (2)(ddpp)(2)(NCS)(4)] x 4
      CH(2)Cl(2) (1 x 4 CH(2)Cl(2); ddpp = 2,5-di(2',2''-dipyridylamino)pyridine) and
      its partially desolvated analogue (1 x CH(2)Cl(2)), which undergo two- and one
      step spin-crossover (SCO) transitions, respectively. Here, we manipulate the type
      and degree of solvation in this system and find that either a one- or two-step
      spin transition can be specifically targeted. The chloroform clathrate 1 x 4
      CHCl(3) undergoes a relatively abrupt one-step SCO, in which the two equivalent
      Fe(II) sites within the dinuclear molecule crossover simultaneously. Partial
      desolvation of 1 x 4 CHCl(3) to form 1 x 3 CHCl(3) and 1 x CHCl(3) occurs through
      single-crystal-to-single-crystal processes (monoclinic C2/c to P2(1)/n to
      P2(1)/n) in which the two equivalent Fe(II) sites become inequivalent sites
      within the dinuclear molecule of each phase. Both 1 x 3 CHCl(3) and 1 x CHCl(3)
      undergo one-step spin transitions, with the former having a significantly higher
      SCO temperature than 1 x 4 CHCl(3) and the latter, and each has a broader SCO
      transition than 1 x 4 CHCl(3), attributable to the overlap of two SCO steps in
      each case. Further magnetic manipulation can be carried out on these materials
      through reversibly resolvating the partially desolvated material with chloroform
      to produce the original one-step SCO, or with dichloromethane to produce a two
      step SCO reminiscent of that seen for 1 x 4 CH(2)Cl(2). Furthermore, we
      investigate the light-induced excited spin state trapping (LIESST) effect on 1 x
      4 CH(2)Cl(2) and 1 x CH(2)Cl(2) and observe partial LIESST activity for the
      former and no activity for the latter.

PMID- 20029915
TI  - Binary Au/MWCNT and ternary Au/ZnO/MWCNT nanocomposites: synthesis,
      characterisation and catalytic performance.
AB  - Gold nanoparticles of 10-24 and 5-8 nm in size were obtained by chemical citrate
      reduction and UV photoreduction, respectively, on acid-treated multiwalled carbon
      nanotubes (MWCNTs) and on ZnO/MWCNT composites. The shape and size of the
      deposited Au nanoparticles were found to be dependent upon the synthetic method
      used. Single-crystalline, hexagonal gold particles were produced in the case of
      UV photoreduction on ZnO/MWCNT, whereas spherical Au particles were deposited on
      MWCNT when the chemical citrate reduction method was used. In the UV
      photoreduction route, n-doped ZnO serves as the e(-) donor, whereas the solvent
      is the hole trap. All materials were fully characterised by UV/Vis spectroscopy,
      scanning electron microscopy, transmission electron microscopy, X-ray
      photoelectron spectroscopy, Raman spectroscopy and BET surface analysis. The
      catalytic activity of the composites was studied for the selective hydrogenation
      of alpha,beta-unsaturated carbonyl compound 3,7-dimethyl-2,6-octadienal (citral).
      The Au/ZnO/MWCNT composite favours the formation of unsaturated alcohols
      (selectivity=50% at a citral conversion of 20%) due to the presence of single
      crystalline, hexagonal gold particles, whereas saturated aldehyde formation is
      favoured in the case of the Au/MWCNT nanocomposite that contains spherical gold
      particles.

PMID- 20029916
TI  - Synthesis and optical properties of europium-complex-doped inorganic/organic
      hybrid materials built from oxo-hydroxo organotin nano building blocks.
AB  - Hybrid materials doped with novel europium complexes were synthesized using PMMA
      co-Sn(12)Clusters (copolymers from oxohydroxo-organotin dimethacrylate and
      methylmethacrylate) as the matrix material. Two types of hybrid materials were
      obtained: the physically doped product, PMMA-co-Sn(12)Cluster/Eu(TTA)(3)phen, and
      the grafted product, PMMA-co-Sn(12)Cluster-co-[EuAA(TTA)(2)phen] (TTA = 2
      thenoyltrifluoroacetone, phen = phenanthroline and AA = acrylic acid). The hybrid
      materials exhibited characteristic luminescence of the Eu(3+) ions, and also
      showed relative especial optical properties compared with samples just using PMMA
      as the matrix material. The PMMA-co-Sn(12)Cluster matrix exhibited a high
      physical doping quantity of [Eu(TTA)(3)phen], which can be attributed to the
      special structure of this kind of hybrid material. GPC (gel-permeation
      chromatography), TGA (thermogravimetric analysis), SEM, (1)H NMR, ICP
      (inductively coupled plasma), (119)Sn NMR, FTIR, and diffuse reflectance
      techniques were employed to characterize the structures and properties of these
      hybrid materials.

PMID- 20029917
TI  - Antithyroid drugs and their analogues protect against peroxynitrite-mediated
      protein tyrosine nitration--a mechanistic study.
AB  - In this paper, the effect of some commonly used antithyroid drugs and their
      analogues on peroxynitrite-mediated nitration of proteins is described. The
      nitration of tyrosine residues in bovine serum albumin (BSA) and cytochrome c was
      studied by Western blot analysis. These studies reveal that the antithyroid drugs
      methimazole (MMI), 6-n-propyl-2-thiouracil (PTU), and 6-methyl-2-thiouracil
      (MTU), which contain thione moieties, significantly reduce the tyrosine nitration
      of both BSA and cytochrome c. While MMI exhibits good peroxynitrite (PN)
      scavenging activity, the thiouracil compounds PTU and MTU are slightly less
      effective than MMI. The S- and Se- methylated compounds show a weak inhibitory
      effect in the nitration of tyrosine, indicating that the presence of a thione or
      selone moiety is important for an efficient inhibition. Similarly, the
      replacement of N-H moiety in MMI by N-methyl or N-m-methoxybenzyl substituents
      dramatically reduces the antioxidant activity of the parent compound. Theoretical
      studies indicate that the substitution of N-H moiety by N-Me significantly
      increases the energy required for the oxidation of sulfur center by PN. However,
      such substitution in the selenium analogue of MMI increases the activity of
      parent compound. This is due to the facile oxidation of the selone moiety to the
      corresponding selenenic and seleninic acids. Unlike N,N'-disubstituted thiones,
      the corresponding selones efficiently scavenge PN, as they predominantly exist in
      their zwitterionic forms in which the selenium atom carries a large negative
      charge.

PMID- 20029918
TI  - Vibrational signature of double-end-linked molecules at Au nanojunctions probed
      by surface-enhanced Raman spectroscopy.

PMID- 20029919
TI  - Sandwich compounds of transition metals with cyclopolyenes and isolobal boron
      analogues.
AB  - A series of sandwich compounds of transition metals (M=Ni, Fe, Cr) with cyclic
      hydrocarbon (M(CH)(n)) and borane (M(BH(2))(n)), ligands (including mixed
      hydrocarbon/borane sandwiches) has been studied using density functional theory
      (B3LYP/6-311+G(df,p)). Multicenter bonding between the central metal atom and
      basal cycloborane rings provides stabilization to planar cycloborane species.
      Large negative NICS values allude to aromatic character in the cycloboranes
      similar to the analogous cyclic hydrocarbons. The ability of cycloborane
      sandwiches to stabilize attached carbocations, radicals and carbanions is also
      assessed.

PMID- 20029920
TI  - Regiocontrolled synthesis of ethene-bridged para-phenylene oligomers based on
      Pt(II)- and Ru(II)-catalyzed aromatization.
AB  - We report the regiocontrolled syntheses of ethene-bridged para-phenylene
      oligomers in three distinct classes by using Pt(II)- and Ru(II)-catalyzed
      aromatization. This synthetic approach has been developed based on twofold
      aromatization of the 1-aryl-2-alkynylbenzene functionality, which proceeds by
      distinct regioselectivity for platinum and ruthenium catalysts. Variable
      temperature NMR spectra provide evidence that large arrays of these oligomers are
      prone to twist from planarity. The UV/Vis and photoluminescence (PL) spectra as
      well as the band gaps of these regularly growing arrays show a pattern of
      extensive pi conjugation with increasing array sizes, except for in one instance.

PMID- 20029921
TI  - The role of solvent on the mechanism of proton transfer to hydride complexes: the
      case of the [W(3)PdS(4)H(3)(dmpe)(3)(CO)](+) cubane cluster.
AB  - The kinetics of reaction of the [W(3)PdS(4)H(3)(dmpe)(3)(CO)](+) hydride cluster
      (1(+)) with HCl has been measured in dichloromethane, and a second-order
      dependence with respect to the acid is found for the initial step. In the
      presence of added BF(4) (-) the second-order dependence is maintained, but there
      is a deceleration that becomes more evident as the acid concentration increases.
      DFT calculations indicate that these results can be rationalized on the basis of
      the mechanism previously proposed for the same reaction of the closely related
      [W(3)S(4)H(3)(dmpe)(3)](+) cluster, which involves parallel first- and second
      order pathways in which the coordinated hydride interacts with one and two acid
      molecules, and ion pairing to BF(4) (-) hinders formation of dihydrogen bonded
      adducts able to evolve to the products of proton transfer. Additional DFT
      calculations are reported to understand the behavior of the cluster in neat
      acetonitrile and acetonitrile-water mixtures. The interaction of the HCl molecule
      with CH(3)CN is stronger than the W-H...HCl dihydrogen bond and so the reaction
      pathways operating in dichloromethane become inefficient, in agreement with the
      lack of reaction between 1(+) and HCl in neat acetonitrile. However, the
      attacking species in acetonitrile-water mixtures is the solvated proton, and DFT
      calculations indicate that the reaction can then go through pathways involving
      solvent attack to the W centers, while still maintaining the coordinated hydride,
      which is made possible by the capability of the cluster to undergo structural
      changes in its core.

PMID- 20029922
TI  - Desymmetrization of 3,3'-bis(acylamino)-2,2'-bipyridine-based discotics: the high
      fidelity of their self-assembly behavior in the liquid-crystalline state and in
      solution.
AB  - Two novel nonsymmetrical disc-shaped molecules 1 and 2 based on 3,3'
      bis(acylamino)-2,2'-bipyridine units were synthesized by means of a statistical
      approach. Discotic 1 possesses six chiral dihydrocitronellyl tails and one
      peripheral phenyl group, whereas discotic 2 possesses six linear dodecyloxy tails
      and one peripheral pyridyl group. Preorganization by strong intramolecular
      hydrogen bonding and subsequent aromatic interactions induce self-assembly of the
      discotics. Liquid crystallinity of 1 and 2 was determined with the aid of
      polarized optical microscopy, differential scanning calorimetry, and X-ray
      diffraction. Two columnar rectangular mesophases (Col(r)) have been identified,
      whereas for C(3)-symmetrical derivatives only one Col(r) mesophase has been
      found. In solution, the molecularly dissolved state in chloroform was studied
      with (1)H NMR spectroscopy, whereas the self-assembled state in apolar solution
      was examined with optical spectroscopy. Remarkably, these desymmetrized
      discotics, which lack one aliphatic wedge, behave similar to the symmetric parent
      compound. To prove that the stacking behavior of discotics 1 and 2 is similar to
      that of reported C(3)-symmetrical derivatives, a mixing experiment of chiral 1
      with C(3)-symmetrical 13 has been undertaken; it has shown that they indeed
      belong to one type of self-assembly. This helical J-type self-assembly was
      further confirmed with UV/Vis and photoluminescence (PL) spectroscopy.
      Eventually, disc 2, functionalized with a hydrogen-bonding acceptor moiety, might
      perform secondary interactions with molecules such as acids.

PMID- 20029923
TI  - Ionic-liquid-grafted rigid poly(p-phenylene) microspheres: efficient
      heterogeneous media for metal scavenging and catalysis.
AB  - Novel guanidinium ionic liquid-grafted rigid poly(p-phenylene) (PPPIL)
      microspheres have been developed for metal scavenging and catalysis. The noble
      metal nanoparticles supported on the microspheres surface can be used as
      efficient heterogeneous catalysts. The combination of nanoparticles and ionic
      liquid fragments on the microsphere surfaces enhance the activity and durability
      of the catalyst. The PPPILPd(0) catalyst has been tested in the Suzuki cross
      coupling reaction, and exhibits much higher catalytic activity than Pd catalysts
      supported on porous polymer matrices. The PPPILPd(0) catalyst can be recycled at
      least for nine runs without any significant loss of activity. The present
      approach may, therefore, have potential applications in transition-metal
      nanocatalyzed reactions.

PMID- 20029924
TI  - Iridium-catalyzed coupling reaction of primary alcohols with 2-alkynes leading to
      hydroacylation products.
AB  - A novel iridium-catalyzed intermolecular coupling reaction of primary alcohols or
      aldehydes with 2-alkynes was successfully achieved with high regioselectivity to
      give hydroacylation products such as alpha,beta-unsaturated ketones in good
      yields. The mechanistic investigation of the reaction strongly indicated that the
      coupling proceeds through the initial formation of homoallylic alcohols followed
      by dehydrogenation to beta,gamma-unsaturated ketones and then isomerisation,
      which leads to the hydroacylation products.

PMID- 20029925
TI  - Substrate-dependent nonlinear effects in proline-thiourea-catalyzed aldol
      reactions: unraveling the role of the thiourea co-catalyst.

PMID- 20029926
TI  - A singularity model for chemical reactivity.
AB  - This article proposes a model for chemical reactivity that involves singularities
      ("catastrophes") in the timing of bond-making and bond-breaking events. The
      common stapler is a good mechanical analogy: As hand-pressure is increased on the
      machine, the staple hardly changes its configuration until the staple suddenly
      bends. This is viewed as a singularity or catastrophe, defined classically as an
      abrupt change resulting from a smooth increase or decrease in external conditions
      (pressure in the case of a stapler, distance in the case of reactivity). Although
      experimental observations are provided to support the singularity effect, the
      model remains a heterodox notion at the present time.

PMID- 20029927
TI  - Reactive intermediates: a transient electrophilic phosphinidene caught in the
      act.

PMID- 20029928
TI  - Medicinal Chemistry of Incretin Mimetics and DPP-4 Inhibitors.

PMID- 20029929
TI  - A comparative study on the lithium-ion storage performances of carbon nanotubes
      and tube-in-tube carbon nanotubes.
AB  - A comparative study of the electrochemical performances of carbon nanotubes and
      tube-in-tube carbon nanotubes reveals a dependence effect of lithium-ion storage
      behavior on the detailed nanostructure of carbon nanotubes. In particular, the
      impurity that graphitic particles or graphene fragments inherently present in
      carbon nanotubes plays a crucial role in the lithium-ion storage capacity of the
      carbon nanotubes. Compared to acid-washed carbon nanotubes, the assembly of
      graphitic impurity fragments in the tube-in-tube structures hinders lithium-ion
      diffusion, thus drastically decreasing the rate performance of lithium-ion
      storage. Significantly, our results indicate that the lithium-ion storage
      capacity of carbon nanotubes as anode electrodes can be improved or controlled by
      optimizing the microstructure composition of impurity graphitic nanoparticles or
      graphene fragments in the matrix of the carbon nanotubes.

PMID- 20029930
TI  - Delivery of macromolecules into live cells by simple co-incubation with a
      peptide.

PMID- 20029932
TI  - Phenotypic plasticity in number of glomeruli and sensory innervation of the
      antennal lobe in leaf-cutting ant workers (A. vollenweideri).
AB  - In the leaf-cutting ant Atta vollenweideri, the worker caste exhibits a
      pronounced size-polymorphism, and division of labor is dependent on worker size
      (alloethism). Behavior is largely guided by olfaction, and the olfactory system
      is highly developed. In a recent study, two different phenotypes of the antennal
      lobe of Atta vollenweideri workers were found: MG- and RG-phenotype (with/without
      a macroglomerulus). Here we ask whether the glomerular numbers are related to
      worker size. We found that the antennal lobes of small workers contain
      approximately 390 glomeruli (low-number; LN-phenotype), and in large workers we
      found a substantially higher number of approximately 440 glomeruli (high-number;
      HN-phenotype). All LN-phenotype workers and some small HN-phenotype workers do
      not possess an MG (LN-RG-phenotype and HN-RG-phenotype), and the remaining
      majority of HN-phenotype workers do possess an MG (HN-MG-phenotype). Using mass
      staining of antennal olfactory receptor neurons we found that the sensory tracts
      divide the antennal lobe into six clusters of glomeruli (T1-T6). In LN-phenotype
      workers, approximately 50 glomeruli are missing in the T4-cluster. Selective
      staining of single sensilla and their associated receptor neurons revealed that
      T4-glomeruli are innervated by receptor neurons from the main type of olfactory
      sensilla, the Sensilla trichodea curvata. The other type of olfactory sensilla
      (Sensilla basiconica) exclusively innervates T6-glomeruli. Quantitative analyses
      of differently sized workers revealed that the volume of T6 glomeruli scales with
      the power of 2.54 to the number of Sensilla basiconica. The results suggest that
      developmental plasticity leading to antennal-lobe phenotypes promotes differences
      in olfactory-guided behavior and may underlie task specialization within ant
      colonies.

PMID- 20029933
TI  - Discounting future health gains: an empirical enquiry into the influence of
      growing life expectancy.
AB  - We tested the influence of the growth in life expectancy over time on social time
      preferences for health. Growing life expectancy of future generations should
      raise social discount rates for health because of diminishing marginal utility of
      additional health gains and equity reasons reflecting the desire for a more
      equitable distribution of benefits over generations. This influence has, however,
      been largely ignored in empirical studies. We provide a first comprehensive
      analysis of how time preferences for health gains vary with projected growth
      rates, indicating the importance of subjective expectations about the growth in
      life expectancy in the elicitation of social time preference. Six hundred and
      fifty-six respondents, representative of the Dutch population, completed one of
      four questionnaires, differing in the projected growth in life expectancy.
      Results showed that individuals discount future health gains at different rates,
      depending on the latency period and on the projected or expected growth in life
      expectancy. As hypothesized, discount rates increased with higher growth rates.
      The association between observed discount rates and expectations regarding future
      life expectancy was confirmed, suggesting that discount rates for health may
      depend on future life expectancy. In light of our results, specifying life
      expectancy of future generations in time preference exercises appears
      appropriate.

PMID- 20029934
TI  - Female germline stem cell niches of earwigs are structurally simple and different
      from those of Drosophila melanogaster.
AB  - Stem cells function in niches, which consist of somatic cells that control the
      stem cells' self-renewal, proliferation, and differentiation. Drosophila ovary
      germline niche consists of the terminal filament (TF) cells, cap cells, and
      escort stem cells; signaling from the TF cells and the cap cells is essential for
      maintenance of germline stem cells (GSCs). Here, we show that in the earwig
      Opisthocosmia silvestris, the female GSC niche is morphologically simple and
      consist of the TF cells and several structurally uniform escort cells. The most
      posterior cell of the TF (the basal cell of the TF) differs from remaining TF
      cells and is separated from the anterior region of the germarium by the processes
      of the escort cells, and consequently, does not contact the GSCs directly. We
      also show that between somatic cells of earwig niche argosome-like vesicles and
      cytoneme-like extensions are present.

PMID- 20029935
TI  - Correction of bias from non-random missing longitudinal data using auxiliary
      information.
AB  - Missing data are common in longitudinal studies due to drop-out, loss to follow
      up, and death. Likelihood-based mixed effects models for longitudinal data give
      valid estimates when the data are missing at random (MAR). These assumptions,
      however, are not testable without further information. In some studies, there is
      additional information available in the form of an auxiliary variable known to be
      correlated with the missing outcome of interest. Availability of such auxiliary
      information provides us with an opportunity to test the MAR assumption. If the
      MAR assumption is violated, such information can be utilized to reduce or
      eliminate bias when the missing data process depends on the unobserved outcome
      through the auxiliary information. We compare two methods of utilizing the
      auxiliary information: joint modeling of the outcome of interest and the
      auxiliary variable, and multiple imputation (MI). Simulation studies are
      performed to examine the two methods. The likelihood-based joint modeling
      approach is consistent and most efficient when correctly specified. However, mis
      specification of the joint distribution can lead to biased results. MI is
      slightly less efficient than a correct joint modeling approach and can also be
      biased when the imputation model is mis-specified, though it is more robust to
      mis-specification of the imputation distribution when all the variables affecting
      the missing data mechanism and the missing outcome are included in the imputation
      model. An example is presented from a dementia screening study.

PMID- 20029937
TI  - Potential surrogate endpoints in cancer research--some considerations and
      examples.
AB  - We present an introductory survey of the use of surrogates in cancer research, in
      particular in clinical trials. The concept of a surrogate endpoint is introduced
      and contrasted with that of a biomarker. It is emphasized that a surrogate
      endpoint is not universal for an indication but will depend on the mechanism of
      treatment. We discuss the measures of validity of a surrogate and give examples
      of both cancer surrogates and biomarkers on the path to surrogacy. Circumstances
      in which a surrogate endpoint may actually be preferred to the clinical endpoint
      are described. We provide pointers to the recent substantive literature on
      surrogates.

PMID- 20029936
TI  - That instrument is lousy! In search of agreement when using instrumental
      variables estimation in substance use research.
AB  - The primary statistical challenge that must be addressed when using cross
      sectional data to estimate the consequences of consuming addictive substances is
      the likely endogeneity of substance use. While economists are in agreement on the
      need to consider potential endogeneity bias and the value of instrumental
      variables estimation, the selection of credible instruments is a topic of heated
      debate in the field. Rather than attempt to resolve this debate, our paper
      highlights the diversity of judgments about what constitutes appropriate
      instruments for substance use based on a comprehensive review of the economics
      literature since 1990. We then offer recommendations related to the selection of
      reliable instruments in future studies.

PMID- 20029938
TI  - Analysis of multiple endpoints in clinical trials: it's time for the designations
      of primary, secondary and tertiary to go.

PMID- 20029939
TI  - Polymorphisms in CRHR1 and the serotonin transporter loci: gene x gene x
      environment interactions on depressive symptoms.
AB  - Gene x environment (G x E) interactions mediating depressive symptoms have been
      separately identified in the stress-sensitive serotonergic (5-HTTLPR) and
      corticotropin-releasing hormone (CRHR1) systems. Our objective was to examine
      whether the effects of child abuse are moderated by gene x gene (G x G)
      interactions between CRHR1 and 5-HTTLPR polymorphisms. We used an association
      study examining G x G x E interactions of CRHR1 and 5-HTTLPR polymorphisms and
      measures of child abuse on adult depressive symptomatology. The participant
      population (N = 1,392) was African-American, of low socioeconomic status (60%
      with <$1,000/month family income), and with high rates of childhood and lifetime
      trauma. Depressive symptoms were measured with Beck Depression Inventory (BDI)
      and history of Major Depression by Structure Clinical Interview based on DSM-IV
      (SCID). We first replicated an interaction of child abuse and 5-HTTLPR on
      lifetime SCID diagnosis of major depression in a subsample (N = 236) of the study
      population-the largest African-American 5-HTTLPR cohort reported to date. We then
      extended our previously reported interaction with both a CRHR1 SNP (rs110402) and
      TCA haplotype interacting with child abuse to predict current symptoms (N =
      1,059; P = 0.0089). We found that the 5-HTTLPR S allele interacted with CRHR1
      haplotypes and child abuse to predict current depressive symptoms (N = 856, P =
      0.016). These data suggest that G x E interactions predictive of depressive
      symptoms may be differentially sensitive to levels of childhood trauma, and the
      effects of child abuse are moderated by genetic variation at both the CRHR1 and 5
      HTTLPR loci and by their G x G interaction.

PMID- 20029941
TI  - A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes
      for autism spectrum disorder.
AB  - High resolution genomic copy-number analysis has shown that inherited and de novo
      copy-number variations contribute significantly to autism pathology, and that
      identification of small chromosomal aberrations related to autism will expedite
      the discovery of risk genes involved. Here, we report a microduplication of
      chromosome 15q11.2, spanning only four genes, co-segregating with autism in a
      Dutch pedigree, identified by SNP microarray analysis, and independently
      confirmed by FISH and MLPA analysis. Quantitative RT-PCR analysis revealed over
      70% increase in peripheral blood mRNA levels for the four genes present in the
      duplicated region in patients, and RNA in situ hybridization on mouse embryonic
      and adult brain sections revealed that two of the four genes, CYFIP1 and NIPA1,
      were highly expressed in the developing mouse brain. These findings point towards
      a contribution of microduplications at chromosome 15q11.2 to autism, and
      highlight CYFIP1 and NIPA1 as autism risk genes functioning in axonogenesis and
      synaptogenesis. Thereby, these findings further implicate defects in dosage
      sensitive molecular control of neuronal connectivity in autism. However, the
      prevalence of this microduplication in patient samples was statistically not
      significantly different from control samples (0.94% in patients vs. 0.42%
      controls, P = 0.247), which suggests that our findings should be interpreted with
      caution and indicates the need for studies that include large numbers of control
      subjects to ascertain the impact of these changes on a population scale.

PMID- 20029940
TI  - Suggestive synergy between genetic variants in TF and HFE as risk factors for
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex disease that is likely influenced by many
      genetic and environmental factors. Citing evidence that iron may play a role in
      AD pathology, Robson et al. [Robson et al. (2004); J Med Genet 41:261-265]
      reported that epistatic interaction between rs1049296 (P589S) in the transferrin
      gene (TF) and rs1800562 (C282Y) in the hemochromatosis gene (HFE) results in
      significant association with risk for AD. In this study we attempted to replicate
      their findings in a total of 1,166 cases and 1,404 controls from three European
      and European American populations. Allele and genotype frequencies were
      consistent across the three populations. Using synergy factor analysis (SFA) and
      Logistic Regression analysis we tested each population and the combined sample
      for interactions between these two SNPs and risk for AD. We observed significant
      association between bi-carriers of the minor alleles of rs1049296 and rs1800562
      in the combined sample using SFA (P = 0.0016, synergy factor = 2.71) and adjusted
      SFA adjusting for age and presence of the APOE epsilon 4 allele (P = 0.002, OR =
      2.4). These results validate those of the previous report and support the
      hypothesis that iron transport and regulation play a role in AD pathology.

PMID- 20029943
TI  - Rituximab as an effective treatment of hyperhemolysis syndrome in sickle cell
      anemia.

PMID- 20029942
TI  - Ethnic differences in anemia among patients with diabetes mellitus: the Diabetes
      Study of Northern California (DISTANCE).
AB  - To examine ethnic differences in hemoglobin testing practices and to test the
      hypothesis that ethnicity is an independent predictor of anemia among patients
      with diabetes mellitus. We conducted a panel study to assess the rate of
      hemoglobin testing during 1999-2001 and the period prevalence and incidence of
      anemia among 79,985 adults with diabetes mellitus receiving care within Kaiser
      Permanente of Northern California. Anemia was defined as hemoglobin <13.0 g/dL in
      men or < 12.0 g/dL in women. Overall, 82.1% of the cohort was tested for anemia
      at least once during the 3-year study period. Mixed ethnicity patients were most
      likely to be tested, followed by whites, blacks, Latinos, and Asians (P <
      0.0001). Fifteen percent of the cohort had prevalent anemia at baseline, and an
      additional 22% of those tested developed anemia during the study period. Anemia
      was more prevalent among blacks and mixed ethnicity persons compared with other
      racial/ethnic groups. Anemia was also more prevalent among those >/=70 years of
      age or with estimated glomerular filtration rate <60 ml/min/1.73 m(2). In
      multivariable models, blacks had higher and Asians had lower odds of prevalent
      anemia and hazard ratios of incident anemia compared with whites. Within a large,
      diverse cohort with diabetes, ethnicity was predictive of anemia, even after
      adjustment for age, level of kidney function, and other potential confounders.
      Blacks with diabetes are at increased risk of anemia relative to whites. These
      differences may account for some of the observed ethnic disparities in diabetes
      complications.

PMID- 20029944
TI  - Genetic polymorphisms in the metabolic pathway and non-Hodgkin lymphoma survival.
AB  - Metabolic pathway enzymes, such as Cytochrome P450 (CYP), glutathione S
      transferase (GST), and N-acetyltransferases (NAT) are involved in activation and
      detoxification of environmental carcinogens as well as drug metabolism. We
      hypothesized that the genetic variations in such metabolic pathways may affect
      NHL prognosis and survival. Follow-up information of 496 female NHL incident
      cases diagnosed during 1996-2000 in Connecticut were abstracted from the
      Connecticut Tumor Registry in 2008; survival analyses were conducted by comparing
      the Kaplan-Meier curves, and hazard ratios (HR) were computed from the Cox
      Proportional Hazard models adjusting for demographic and tumor characteristics
      which were suggested by previous studies to be determinants of NHL survival. We
      identified six SNPs from four metabolism genes (CYP2E1, GSTP1, GSTT1, and NAT1)
      that were associated with NHL survival. Specifically, polymorphisms in GSTT1 were
      associated with follicular lymphoma survival; and polymorphisms in CYP2E1, GSTP1,
      and NAT1 were associated with survival of chronic lymphocytic leukemia/small
      lymphocytic lymphoma. Our study suggests that genetic polymorphisms in metabolic
      pathways may help improve the prediction of NHL survival and prognosis.

PMID- 20029945
TI  - Endothelial nitric oxide synthase and nitric oxide regulate endothelial tissue
      factor expression in vivo in the sickle transgenic mouse.
AB  - Activation of the coagulation system is a characteristic feature of sickle cell
      anemia, which also includes clinical thrombosis. The sickle transgenic mouse
      abnormally expresses tissue factor (TF) on the pulmonary vein endothelium.
      Knowing that this aberrancy is stimulated by inflammation, we sought to determine
      whether nitric oxide (NO) contributes to regulation of endothelial TF expression
      in the sickle mouse model. We used the NY1DD sickle mouse, which exhibits a low
      TF to high-TF phenotype switch on exposure to hypoxia/reoxygenation.
      Manipulations of NO biology, such as breathing NO or addition of arginine or L
      NAME (N-nitro-L-arginine-methyl-ester) to the diet, caused significant
      modulations of TF expression. This was also seen in hBERK1 sickle mice, which
      have a different genetic background and already have high-TF even at ambient air.
      Study of NY1DD animals bred to overexpress endothelial nitric oxide synthase
      (eNOS; eNOS-Tg) or to have an eNOS knockout state (one eNOS(-/-) animal and
      several eNOS(+/-) animals) demonstrated that eNOS modulates endothelial TF
      expression in vivo by down-regulating it. Thus, the biodeficiency of NO
      characteristic of patients with sickle cell anemia may heighten risk for
      activation of the coagulation system.

PMID- 20029946
TI  - Finally, a consensus statement on sickle cell disease manifestations: a critical
      step in improving the medical care and research agenda for individuals with
      sickle cell disease.

PMID- 20029947
TI  - Prognosis and survivorship in primary myelofibrosis.

PMID- 20029948
TI  - Endogenous thrombin potential in the assessment of hypercoagulability in systemic
      lupus erythematosus.

PMID- 20029949
TI  - HIV-negative, HHV-8-unrelated primary effusion lymphoma-like lymphoma: report of
      two cases.

PMID- 20029951
TI  - The number of people with sickle-cell disease in the United States: national and
      state estimates.

PMID- 20029950
TI  - Cardiopulmonary complications leading to premature deaths in adult patients with
      sickle cell disease.
AB  - Sickle cell disease (SCD) is associated with early mortality. We sought to
      determine the incidence, cause, and risk factors for death in an adult population
      of patients with SCD. All patients aged >/=18 years seen at the Adult Sickle Cell
      Center at Duke University Medical Center between January 2000 and April 2005 were
      enrolled. Forty-three patients (21 males and 22 females) died during the study
      period. The median age of survival was 39 years for females (95% CI: 34-56), 40
      years for males (95% CI: 34-48), and 40 years overall (95% CI: 35-48). Cardiac
      causes of death accounted for 25.6% (11/43 patients); pulmonary, 14.0% (six
      patients); other SCD related, 32.6% (14 patients); unknown, 14.0% (six patients);
      and others, 14.0% (six patients). Pulseless electrical activity arrest, pulmonary
      emboli, multiorgan failure, and stroke were the most frequent causes of death.
      Among the deceased patients, the most common premorbid conditions were
      cardiopulmonary: acute chest syndrome/pneumonia (58.1%), Pulmonary hypertension
      (pHTN; 41.9%), systemic HTN (25.6%), congestive heart failure (25.6%), myocardial
      infarction (20.9%), and arrhythmias (14.0%). Tricuspid regurgitant jet velocity
      was significantly higher (3.1 m/sec vs. 2.6 m/sec, P < 0.001) and hemoglobin
      significantly lower (8.3 g/dL vs. 9.2 g/dL, P < 0.05) in deceased patients when
      compared with patients who lived, respectively. With improved preventive and
      therapeutic advances, including hydroxyurea therapy, acute complications such as
      infection are no longer the leading cause of death; instead, causes of death and
      premorbid conditions are shifting to chronic cardiopulmonary complications.
      Further, arrhythmia leading to premature death is under-recognized in SCD and
      warrants further investigation.

PMID- 20029952
TI  - Genetic modifiers of the severity of sickle cell anemia identified through a
      genome-wide association study.
AB  - We conducted a genome-wide association study (GWAS) to discover single nucleotide
      polymorphisms (SNPs) associated with the severity of sickle cell anemia in 1,265
      patients with either "severe" or "mild" disease based on a network model of
      disease severity. We analyzed data using single SNP analysis and a novel SNP set
      enrichment analysis (SSEA) developed to discover clusters of associated SNPs.
      Single SNP analysis discovered 40 SNPs that were strongly associated with sickle
      cell severity (odds for association >1,000); of the 32 that we could analyze in
      an independent set of 163 patients, five replicated, eight showed consistent
      effects although failed to reach statistical significance, whereas 19 did not
      show any convincing association. Among the replicated associations are SNPs in
      KCNK6 a K(+) channel gene. SSEA identified 27 genes with a strong enrichment of
      significant SNPs (P < 10(-6)); 20 were replicated with varying degrees of
      confidence. Among the novel findings identified by SSEA is the telomere length
      regulator gene TNKS. These studies are the first to use GWAS to understand the
      genetic diversity that accounts the phenotypic heterogeneity sickle cell anemia
      as estimated by an integrated model of severity. Additional validation,
      resequencing, and functional studies to understand the biology and reveal
      mechanisms by which candidate genes might have their effects are the future goals
      of this work.

PMID- 20029953
TI  - Transfusion-dependency at presentation and its acquisition in the first year of
      diagnosis are both equally detrimental for survival in primary myelofibrosis-
      prognostic relevance is independent of IPSS or karyotype.
AB  - The International Prognostic Scoring System (IPSS) and karyotype are useful tools
      for risk stratification in primary myelofibrosis (PMF). We examined the
      additional prognostic impact of red blood cell transfusion need among 254
      consecutive patients (median age, 59 years). Sixty-two patients ( approximately
      24%) required transfusions at diagnosis whereas 22 ( approximately 9%) became
      transfusion-dependent and 170 remained transfusion-independent during the first
      year postdiagnosis; after a median follow-up of 55 months, the respective median
      survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis
      confirmed the IPSS- and karyotype-independent prognostic weight of transfusion
      status. Among IPSS intermediate-1 risk patients, overall median survival of 82
      months was modified to 60 or 118 months, based on presence or absence of
      transfusion need, respectively (P < 0.01). The corresponding figures for
      intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented
      causes of death did not include iron overload. We conclude that transfusion
      status in PMF downgrades or upgrades prognosis within specific IPSS categories;
      transfusion need is a marker of aggressive disease biology in PMF, as it is in
      myelodysplastic syndromes.

PMID- 20029954
TI  - Costs and length of stay for patients with and without sickle cell disease after
      hysterectomy, appendectomy, or knee replacement.

PMID- 20029955
TI  - Tumor flare reactions and response to lenalidomide in patients with refractory
      classic Hodgkin lymphoma.

PMID- 20029956
TI  - Decrease of adenosine deaminase activity and increase of the lipid peroxidation
      after acute methotrexate treatment in young rats: protective effects of grape
      seed extract.
AB  - The methotrexate (MTX) is an anti-folate used to treat cancer and some
      inflammatory diseases. The efficacy of MTX is often limited by its severe
      toxicity. The present study was undertaken to determine whether Grape seed
      (Cabernet Sauvignon) extract (GSE) could ameliorate the MTX-induced oxidative
      injury and the effect on adenosine deaminase activity (ADA) in rats. The rats
      were pretreated with 50 mg/kg of GSE, i.p., prior to MTX administration (10
      mg/kg, i.p.) with a second dose given 4 h and a third dose 16 h after MTX
      administration. Biochemical parameters were investigated 48 h after the last MTX
      administration. The administration of MTX increased thiobarbituric acid reactive
      species (TBARS) levels in hippocampus, kidney and liver, whereas induced a
      significant decreased in the ADA activity in the cerebral cortex, kidney and
      liver tissues. MTX administration significantly increased the activity of
      ALT(alanine aminotransferase) and urea levels and decreased uric acid levels in
      the serum. Urinary uric acid levels decreased in the MTX group when compared to
      those of the control group. The GSE along with MTX-administration significantly
      reversed these parameters toward to near normal. These results indicated that GSE
      could reduce hepatic and nephritic damage induced by MTX-treatment in young rats
      therefore having free radical scavenging.

PMID- 20029957
TI  - The effects of Nigella sativa on bile duct ligation induced-liver injury in rats.
AB  - Nigella sativa (NS) has been shown to have antioxidant and antiinflammatory
      activities in different conditions. The goal of this study was to evaluate the
      effects of NS on cholestatic liver injury in rats. Thirty rats were recruited in
      the study as follows: Group 1, Bile duct ligation (BDL) (n = 10); Group 2, BDL
      plus NS (n = 10); and Group 3, Sham (n = 10). Bile duct ligated group received
      0.2 mL kg(-1) dose of NS intraperitoneally daily throughout 14 days. Liver damage
      and cholestasis were determined by the biochemical and the pathologic
      examination. Data showed a decrease in gamma glutamyl transferase (GGT), alkaline
      phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), and lactate dehydrogenase (LDH) activities of the NS treated rats when
      compared with BDL group (p < 0.001 for GGT and p < 0.05 for others). The NS
      treated rats' tissue levels of total oxidant status (TOS), oxidative stress index
      (OSI), and myeloperoxidase (MPO) were significantly lower than that of the BDL
      group (p < 0.01 for all). Increases in total antioxidant capacity (TAC) and
      catalase (CAT) levels were statistically significant in the NS treated rats
      compared to BDL group (p < 0.01 for both). On the other hand, administration of
      NS in the rats with biliary obstruction resulted in inhibition of necro
      inflammation. These results indicate that NS exerts a therapeutic effect on
      cholestatic liver injury in bile duct ligated rats possibly through attenuation
      of enhanced neutrophil infiltration and oxidative stress in the liver tissue.

PMID- 20029958
TI  - Dose-dependent actions of curcumin in experimentally induced myocardial necrosis:
      a biochemical, histopathological, and electron microscopic evidence.
AB  - Curcumin, an active component of turmeric, is a well-known antioxidant due to its
      reactive oxygen species (ROS) scavenging property. However, some in vitro studies
      have suggested that curcumin induces generation of ROS at higher doses and thus
      exerts pro-oxidant effect. We demonstrate, for the first time, the dose-dependent
      effects of curcumin in isoprenaline-induced model of myocardial necrosis in rats.
      The animals were assigned to control, isoprenaline and three curcumin treatment
      groups. Curcumin (100, 200, and 400 mg/kg) and vehicle (dimethyl sulfoxide) were
      administrated orally for 15 days and isoprenaline (85 mg/kg, s.c.) was given to
      curcumin treated and isoprenaline group on 13th and 14th day, respectively.
      Thereafter, on 15th day, the animals were sacrificed for biochemical analysis
      along with histopathological and ultrastructural examination. There was an
      increase in glutathione, superoxide dismutase (SOD), creatine kinase-MB (CK-MB)
      and lactate dehydrogenase (LDH) levels, decrease in thiobarbituric acid reactive
      substances (TBARS), and preservation of myocardial architecture in the curcumin
      (100 and 200 mg/kg) treated groups. However, at 400 mg/kg dose there was
      ineffectual protection against isoprenaline-induced myocardial damage. Instead,
      there was significant lipid peroxidation as evident by increased levels of TBARS
      (93.87 +/- 9.93, p < 0.0001) and decrease in CK-MB (206.32 +/- 13.54, p < 0.0001)
      and LDH (134.26 +/- 9.13, p < 0.01) as compared to the two lower doses. Hence, it
      can be concluded that curcumin augments endogenous antioxidant system at lower
      doses but mediates ROS induction at higher concentration leading to myocardial
      damage.

PMID- 20029959
TI  - Protein disulfide isomerase chaperone ERP-57 decreases plasma membrane expression
      of the human GnRH receptor.
AB  - Retention of misfolded proteins by the endoplasmic reticulum (ER) is a quality
      control mechanism involving the participation of endogenous chaperones such as
      calnexin (CANX). CANX interacts with and restricts plasma membrane expression
      (PME) of the gonadotropin releasing hormone receptor (GnRHR), a G protein-coupled
      receptor. CANX also interacts with ERP-57 a thiol oxidoreductase chaperone
      present in the ER. CANX along with ERP-57 promotes the formation of disulfide
      bond bridges in nascent proteins. The human GnRH receptor (hGnRHR) is stabilized
      by two disulfide bond bridges (C(14)-C(200) and C(114)-C(196)), that, when
      broken, lead to a decrease in receptor expression at the plasma membrane. To
      determine if the presence of chaperones CANX and ERP-57 exerts an influence over
      membrane routing and second messenger activation, we assessed the effect of
      various mutants including those with broken disulfide bridges (Cys --> Ala) along
      with the hGnRHR. The effect of chaperones on mutants was insignificant, whereas
      the over expression of ERP-57 led to an hGnRHR retention. This effect was further
      enhanced by cotransfection with cDNA for CANX showing receptor retention by ERP
      57 augmented by CANX, suggesting utilization of these chaperones for quality
      control of the GnRHR.

PMID- 20029960
TI  - The inhibitory effects of rosiglitazone on cardiac hypertrophy through modulating
      the renin-angiotensin system in diet-induced hypercholesterolemic rats.
AB  - Cardiac hypertrophy is not only an adaptational state before heart failure but
      also is an independent risk factor for ischemia, arrhythmia, and sudden death.
      However, the direct effects of hypercholesterolemia on the myocardium and
      mechanisms are not completely understood. It has been demonstrated that
      peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand agonists
      attenuate cardiac hypertrophy through anti-inflammatory effects. The present
      study investigated the effects of PPARgamma agonists on hypercholesterolemia
      dependent, renin-angiotensin-system-related cardiac hypertrophy. The findings
      showed that left ventricular hypertrophy, eminent cardiomyocyte hypertrophy, and
      lipid deposits in myocardium were observed in the rats fed a cholesterol-rich
      diet for 6 months, while these characteristic pathological alterations and the
      increase in angiotensin II (ANG II) level and over-expression of angiotensin II
      type 1 receptor (AT(1)R) in the left ventricular tissues induced by the
      cholesterol-rich diet were significantly suppressed to equal extents by
      rosiglitazone and irbesartan. In contrast, expression of angiotensin II type 2
      receptor (AT(2)R) was upregulated by these two drugs. In addition, lipid
      metabolism was markedly improved. The above findings suggest that the
      cardioprotection of the PPARgamma agonist against cardiac hypertrophy evoked by
      hypercholesterolemia in rats is mediated partially by the improvement of lipid
      profile, the reduction of ANG II level in the local tissue along with the
      downregulation of AT(1)R expression, and upregulation of AT(2)R expression.

PMID- 20029961
TI  - Enantioseparation of benzazoles and benzanilides on polysaccharide-based chiral
      columns.
AB  - The chiral recognition ability of the polysaccharide-based chiral columns
      (Chiralpak AD-RH, Chiralpak AS-RJ, Chiralpak IC, Chiralcel OD-RH, and Chiralcel
      OJ-RH) for the benzazoles and the benzanilides was evaluated under reversed phase
      conditions. The columns showed the high chiral recognition ability for a wide
      range of benzazoles and benzanilides. Twenty-one racemates were used for the
      evaluation, and 20 racemates were completely separated on at least one of the
      columns. In particular, AS-RH and OJ-RH showed the high chiral recognition
      ability for the benzazoles, and the AD-RH, IC, and OJ-RH were effective for the
      benzanilides.

PMID- 20029962
TI  - P2X7 receptors mediate ischemic damage to oligodendrocytes.
AB  - Brain ischemia leading to stroke is a major cause of disability in developed
      countries. Therapeutic strategies have most commonly focused on protecting
      neurons from ischemic damage. However, ischemic damage to white matter causes
      oligodendrocyte death, myelin disruption, and axon dysfunction, and it is
      partially mediated by glutamate excitotoxicity. We have previously demonstrated
      that oligodendrocytes express ionotropic purinergic receptors. The objective of
      this study was to investigate the role of purinergic signaling in white matter
      ischemia. We show that, in addition to glutamate, enhanced ATP signaling during
      ischemia is also deleterious to oligodendrocytes and myelin, and impairs white
      matter function. Thus, ischemic oligodendrocytes in culture display an inward
      current and cytosolic Ca(2+) overload, which is partially mediated by P2X7
      receptors. Indeed, oligodendrocytes release ATP after oxygen and glucose
      deprivation through the opening of pannexin hemichannels. Consistently, ischemia
      induced mitochondrial depolarization as well as oxidative stress culminating in
      cell death are partially reversed by P2X7 receptor antagonists, by the ATP
      degrading enzyme apyrase and by blockers of pannexin hemichannels. In turn,
      ischemic damage in isolated optic nerves, which share the properties of brain
      white matter, is greatly attenuated by all these drugs. Ultrastructural analysis
      and electrophysiological recordings demonstrated that P2X7 antagonists prevent
      ischemic damage to oligodendrocytes and myelin, and improved action potential
      recovery after ischemia. These data indicate that ATP released during ischemia
      and the subsequent activation of P2X7 receptor is critical to white matter demise
      during stroke and point to this receptor type as a therapeutic target to limit
      tissue damage in cerebrovascular diseases.

PMID- 20029963
TI  - Taurine stimulates proliferation of mice embryonic cultured neural progenitor
      cells.
AB  - Taurine is present in high levels in fetal brain which decrease in the adult,
      suggesting its role in brain development. In some regions of taurine deficient
      animals cells show defective migration and the presence of numerous mitotic
      figures, suggesting a delay in cell proliferation. To know more about the role of
      taurine in the developing brain cells, the present study investigated whether
      taurine is a factor involved in proliferation or/and viability of neural
      progenitor cells (NPC). NPC were obtained from 13.5-days mice embryos
      mesencephalon, and cultured during 4-5 days to form neurospheres in the presence
      of EGF plus FGFb (EGF/FGF) or EGF alone. Mesencephalon taurine content (349
      mmoles/kg protein) was lost in NPC and recovered after addition of 10 mM taurine
      to the culture. Neurospheres-forming NPC were over 94% nestin-positive. Taurine
      increased 38.6% and 43.2% the number of NPC formed in EGF/FGF or EGF conditions,
      respectively. In secondary neurospheres this increase was 24.6% and 62.1%, in
      EGF/FGF or EGF cultures respectively. Correspondingly neurospheres size was
      increased by taurine but neurospheres number was not enhanced. Taurine
      significantly increased the number of BrdU-positive cells, without affecting cell
      viability, suggesting proliferation as the mechanism responsible for taurine
      action increasing NPC. Taurine seems unable to increase the number of beta-III
      tubulin-positive cells differentiated from neurospheres after serum addition, and
      rather an increase in astrocytes was observed. These results point to taurine as
      a trophic factor contributing to optimize NPC proliferation.

PMID- 20029964
TI  - Mobilization of CD133(+)CD34(-) cells in healthy individuals following whole-body
      acupuncture for spinal cord injuries.
AB  - Acupuncture can alleviate symptoms of spinal cord injuries (SCI). The underlying
      mechanism, however, is unknown. We hypothesized that stem cells could be
      mobilized by acupuncture. Therefore, we enrolled 14 healthy study participants
      using acupuncture points for the treatment of SCI. The frequency of CD133 and
      CD34 cells in peripheral blood and the serum concentrations of matrix
      metalloproteinase (MMP)-9, brain-derived neurotrophic factor (BDNF), nerve growth
      factor (NGF), and interleukin-6 were determined before and after acupuncture (<1
      hr, 24 hr, and 48 hr). CD133(+)34(-) cells were doubled 48 hr after acupuncture,
      with concomitant decreases in BDNF and MMP-9 levels. Interleukin-6 remained below
      detectable levels, eliminating a stress-induced cell release. Individuals
      acupunctured on control counterpoints showed no changes in CD133(+) cells. Our
      results indicate that acupuncture for SCI can mobilize human CD133(+)34(-) cells.
      (c) 2009 Wiley-Liss, Inc.

PMID- 20029965
TI  - A mouse model to dissect progesterone signaling in the female reproductive tract
      and mammary gland.
AB  - Considering the regulatory complexities of progesterone receptor (PR) action
      throughout the female reproductive axis and mammary gland, we generated a mouse
      model that enables conditional ablation of PR function in a spatiotemporal
      specific manner. Exon 2 of the murine PR gene was floxed to generate a
      conditional PR allele (PR(flox)) in mice. Crossing the PR(flox/flox) mouse with
      the ZP3-cre transgenic demonstrated that the PR(flox) allele recombines to a PR
      null allele (PR(d)). Mice homozygous for the recombined null PR allele (PR(d/d))
      exhibit uterine, ovarian, and mammary gland defects that phenocopy those of our
      previously described PR knockout (PRKO) model. Therefore, this conditional mouse
      model for PR ablation represents an invaluable resource with which to further
      define in a developmental and/or reproductive stage-specific manner the
      individual and integrative roles of distinct PR populations resident in multiple
      progesterone-responsive target sites.

PMID- 20029966
TI  - Angiogenesis and vascular targeting in Ewing sarcoma: a review of preclinical and
      clinical data.
AB  - Ewing sarcoma is the second most common type of bone cancer in children and young
      adults. In recent years, the mechanisms by which these tumors develop and
      maintain their vascular supply have been elucidated. Additional work has
      demonstrated that inhibition of angiogenic pathways or disruption of established
      vasculature can attenuate the growth of Ewing sarcoma mouse xenografts. Early
      clinical data suggest that these results also may extend to patients with Ewing
      sarcoma who are treated with antiangiogenic or antivascular therapies. For the
      current review, the authors summarized the available data supporting this
      approach.

PMID- 20029967
TI  - Differentiation and behavior of human neural progenitors on micropatterned
      substrates and in the developing retina.
AB  - In this study we investigated the differentiation of human neural progenitor
      cells (hNPCs) in vitro to evaluate their differentiation potential and in vivo to
      explore their viability and behavior following transplantation. Progenitors were
      maintained as neurospheres in media containing basic fibroblast growth factor and
      epidermal growth factor. Micropatterned polystyrene substrates were fabricated
      and coated with ECL (entactin, collagen, and laminin) to provide physical and
      chemical guidance during the differentiation of the hNPCs. The hNPCs growing on
      the micropatterned substrates showed no differences in proliferation or
      differentiation potential compared with those hNPCs growing on the nonpatterned
      substrates. However, hNPCs cultured on the micropatterned substrates were aligned
      in the direction of the micropattern compared with those cells growing on the
      nonpatterned substrates. Furthermore, hNPC migration was directed in alignment
      with the micropatterned substrates. Transplantation of the hNPCs into the
      developing retina was used to evaluate their behavior in vivo. Cells displayed
      extensive survival, differentiation, and morphological integration following
      xenotransplant into the retina, even in the absence of immunosuppression. Taken
      together, our results show that these multipotent hNPCs are a neurogenic
      progenitor population that can be maintained in culture for extended periods.
      Although the micropatterned substrates have no major effect on the proliferation
      or differentiation of the hNPCs, they clearly promoted alignment and directed
      neurite outgrowth along the pattern as well as directing migration of the cells.
      These approaches may provide important strategies to guide the growth and
      differentiation of NPCs in vitro and in vivo.

PMID- 20029968
TI  - Complex care systems in developing countries: breast cancer patient navigation in
      Ethiopia.
AB  - BACKGROUND: As the global visibility and importance of breast cancer increases,
      especially in developing countries, ensuring that countries strengthen and
      develop health systems that support prevention, diagnosis, and treatment of a
      complex chronic disease is a priority. Understanding how breast cancer patients
      navigate health systems to reach appropriate levels of care is critical in
      assessing and improving the health system response in countries to an increasing
      breast cancer burden in their populations. Ethiopia has accelerated attention to
      breast cancer, expanding clinical and public health efforts at diagnosing and
      treating breast cancer earlier and more efficiently. METHODS: This project used a
      mixed-method approach to assessing patient navigation of the healthcare system
      that resulted in care at the cancer referral hospital for Ethiopia (Tikur Anbessa
      Hospital [TAH]). In total, 69 patients representative of the entire breast cancer
      clinical population at TAH were interviewed. RESULTS: Navigation chains are
      widely divergent and typically involve 3 or more care nodes until they reach the
      referral hospital. Patients who consult traditional healers have significantly
      more care nodes to reach the referral hospital than others, and patients who have
      direct access to local and regional hospitals have the smallest number of care
      nodes. Patients report moving laterally from 1 health institution to another or
      regressing to lower levels of care, sometimes complicated by reinvolving
      traditional healers. CONCLUSIONS: The care system can be streamlined for breast
      cancer patients in Ethiopia to facilitate patient access to available and
      clinically effective diagnostic and treatment services in the country, largely
      through improving local primary care and hospital capacity to provide basic
      breast cancer services and improve detection and referral.

PMID- 20029969
TI  - Involvement of brain-derived neurotrophic factor (BDNF) in the functional
      elimination of synaptic contacts at polyinnervated neuromuscular synapses during
      development.
AB  - We use immunohistochemistry to describe the localization of brain-derived
      neurotrophic factor (BDNF) and its receptors trkB and p75(NTR) in the
      neuromuscular synapses of postnatal rats (P6-P7) during the synapse elimination
      period. The receptor protein p75(NTR) is present in the nerve terminal, muscle
      cell and glial Schwann cell whereas BDNF and trkB proteins can be detected mainly
      in the pre- and postsynaptic elements. Exogenously applied BDNF (10 nM for 3 hr
      or 50 nM for 1 hr) increases ACh release from singly and dually innervated
      synapses. This effect may be specific for BDNF because the neurotrophin NT-4 (2-8
      nM) does not modulate release at P6-P7. Blocking the receptors trkB and p75(NTR)
      (with K-252a and anti-p75-192-IgG, respectively) completely abolishes the
      potentiating effect of exogenous BDNF. In addition, exogenous BDNF transiently
      recruits functionally depressed silent terminals, and this effect seems to be
      mediated by trkB. Calcium ions, the L-type voltage-dependent calcium channels and
      protein kinase C are involved in BDNF-mediated nerve ending recruitment. Blocking
      experiments suggest that endogenous BDNF could operate through p75(NTR) receptors
      coupled to potentiate ACh release in all nerve terminals because the anti-p75-192
      IgG reduces release. However, blocking the trkB receptor (K-252a) or neutralizing
      endogenous BDNF with the trkB-IgG fusion protein reveals a trkB-mediated release
      inhibition on almost mature strong endings in dual junctions. Taken together
      these results suggest that a BDNF-induced p75(NTR)-mediated ACh release
      potentiating mechanism and a BDNF-induced trkB-mediated release inhibitory
      mechanism may contribute to developmental synapse disconnection.

PMID- 20029970
TI  - Evaluation of direct medical costs of hospitalization for febrile neutropenia.
AB  - BACKGROUND: Treatment of febrile neutropenia (FN) is costly, because it typically
      involves hospitalization. As cancer rates continue to increase, the number of
      patients suffering from FN will also increase, making it important to quantify
      the costs of treating this condition accurately and comprehensively. METHODS: A
      consecutive sample of patients admitted to an inpatient hematology/oncology ward
      at a tertiary care hospital for the treatment of chemotherapy-induced FN was
      enrolled in this study. Patients were followed prospectively during
      hospitalization, and information on medical resource utilization including length
      of stay, medications, and laboratory and diagnostic tests was collected. Costs,
      extracted from hospital and provincial databases, were used to calculate the
      overall cost per FN episode, from the hospital perspective. RESULTS: Fifty-one
      episodes of FN that occurred in 46 patients were included in the study.
      Approximately 52% of these episodes occurred in women, and 65% of these episodes
      occurred in patients with hematologic malignancies. The mean +/- standard
      deviation age of patients was 60.3 +/- 13.4 years. The mean length of stay per
      episode was 6.8 +/- 4.9 days. The mean overall cost per episode was 6324 +/- 4783
      in 2007 Canadian dollars. CONCLUSIONS: Hospitalization for the treatment of FN is
      expensive. The results of this study could be used in future economic evaluations
      of preventive measures and treatments for FN, including primary prophylactic
      administration of hematopoietic growth factors and outpatient treatment of this
      condition.

PMID- 20029971
TI  - Intracellular calcium and calmodulin link brain-derived neurotrophic factor to
      p70S6 kinase phosphorylation and dendritic protein synthesis.
AB  - The mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway plays an
      important role in brain-derived neurotrophic factor (BDNF)-mediated protein
      synthesis and neuroplasticity. Although many aspects of neuronal function are
      regulated by intracellular calcium ([Ca(2+)](i)) and calmodulin (CaM), their
      functions in BDNF-induced phosphorylation of p70S6K and protein synthesis are
      largely unknown. Here, we report that BDNF, via TrkB-dependent activation of
      mTOR, induces sustained phosphorylation of p70S6K at Thr389 and Thr421/Ser424.
      BDNF-induced phosphorylation at Thr389 was dependent on PI3 kinase but
      independent of ERK-MAPK. The previously identified MAPK phosphorylation site at
      Thr421/Ser424 required both PI3K and MAPK in BDNF-stimulated neurons.
      Furthermore, we found that the reduction in [Ca(2+)](i), but not extracellular
      calcium, blocked the BDNF-induced phosphorylation of p70S6K at both sites.
      Inhibition of CaM by W13 also blocked p70S6K phosphorylation. In correlation, W13
      inhibited BDNF-induced local dendritic protein synthesis. Interestingly,
      sustained elevation of [Ca(2+)](i) by membrane depolarization antagonized the
      BDNF-induced p70S6K phosphorylation. Finally, the BDNF-induced p70S6K
      phosphorylation did not require the increase of calcium level through either
      extracellular influx or PLC-mediated intracellular calcium release. Collectively,
      these results indicate that the basal level of intracellular calcium gates BDNF
      induced activation of p70S6K and protein synthesis through CaM. (c) 2009 Wiley
      Liss, Inc.

PMID- 20029973
TI  - Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis
      of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients
      from the Adult Lymphoma Study Group.
AB  - BACKGROUND: Nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a
      rare entity. METHODS: A clinical registry was launched from 1973 to 2003 in
      France. To determine the histologic transformation (HT) rate to diffuse large B
      cell lymphoma (DLBCL) and long-term outcomes, 164 patients were selected after
      histologic review. RESULTS: The median follow-up was 9.5 years. The high biopsy
      rate (85%) at each recurrence enabled the analysis of HT. The median patient age
      was 30 years (range, 6-69 years), 80% of patients were men, 83% had Ann Arbor
      stage I/II disease, 65% had supradiaphragmatic-disease; 27% received
      radiotherapy, 9% received chemotherapy, 29% received combined-modality therapy,
      and 35% were followed with a watch-and-wait strategy. All 106 treated patients
      achieved complete remission and 66 patients developed disease recurrence at a
      median of 3.3 years (range, 0.4-18.3 years after diagnosis). The majority of
      recurrences were NLPHL, but 19 patients progressed to DLBCL at a median of 4.7
      years (range, 0.4-18 years after diagnosis). The 10-year cumulative HT rate was
      12% and was found to be associated significantly with a poor prognosis. The 10
      year overall survival rate was 91%. Fourteen patients died (7 died of progressive
      disease, 3 died of secondary cancers, and 4 died from other causes). HT was
      diagnosed at a median of 4.7 years (range, 0.4-18 years after diagnosis). The 19
      patients who had HT were treated with curative intent: Nine patients received
      high-dose therapy with subsequent autologous stem cell transplantation (ASCT),
      and 10 patients received different chemotherapy regimens. The overall survival
      rate after HT did not differ between patients who underwent ASCT and the others.
      CONCLUSIONS: This long-term follow-up study confirmed that NLPHL is a separate
      entity that has a favorable clinical presentation and outcome despite frequent
      recurrences. The current findings also emphasize the importance of biopsies at
      the time patients develop recurrent disease to evaluate HT.

PMID- 20029972
TI  - Cervical cancer incidence among 6 asian ethnic groups in the United States, 1996
      through 2004.
AB  - BACKGROUND: Cervical cancer incidence was evaluated by histologic type, age at
      diagnosis, and disease stage for 6 Asian ethnic groups residing in the United
      States. METHODS: Incidence rates were estimated for cervical squamous cell
      carcinoma (SCC) and adenocarcinoma by age and stage for 6 Asian ethnic groups
      Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, and Vietnamese-in 5
      US cancer registry areas during 1996 through 2004. For comparison, rates among
      non-Hispanic whites, non-Hispanic blacks, and Hispanics were also calculated.
      RESULTS: During 1996 through 2004, Vietnamese women had the highest (18.9 per
      100,000) and Asian Indian/Pakistani women had the lowest (4.5) incidence of
      cervical cancer; this pattern was consistent by histologic type. Vietnamese women
      also had the highest incidence for localized (7.3) and regional (5.7) SCC and for
      localized (2.4) adenocarcinoma. Contrary to the plateau of SCC incidence apparent
      among white women by age 45 years, SCC rates continued to rise with age among
      Chinese, Filipina, Korean, and Vietnamese women. CONCLUSIONS: There exists large
      variation in invasive cervical cancer incidence patterns among Asian ethnic
      groups in the United States and in comparison with rates for blacks, Hispanics,
      and whites. Early detection and prevention strategies for cervical cancer among
      Asians require targeted strategies by ethnic group.

PMID- 20029974
TI  - Quality of life after adjuvant intra-arterial chemotherapy and radiotherapy
      versus surgery alone in resectable pancreatic and periampullary cancer: a
      prospective randomized controlled study.
AB  - BACKGROUND: Adjuvant therapies for pancreatic and periampullary cancer reportedly
      achieve only a marginal survival benefit. In this randomized controlled trial,
      120 patients with resected pancreatic or periampullary cancer received either
      adjuvant celiac axis infusion chemotherapy combined with radiotherapy (CAI/RT) or
      no adjuvant treatment. The objective of the study was to compare the quality of
      life (QoL) in patients who received CAI/RT after pancreatoduodenectomy with the
      QoL in patients who did not receive adjuvant treatment. METHODS: During and after
      CAI/RT, QoL was assessed using the European Organization for Research and
      Treatment of Cancer QoL Questionnaire C30 every 3 months during the first 24
      months after randomization. RESULTS: Eighty-six percent of patients (n = 103)
      completed 1 or more questionnaires. In total, 355 questionnaires were completed.
      The results indicated that CAI/RT did not impair physical, emotional, or social
      functioning. During and after CAI/RT, patients had significantly less pain (P =
      .02) and less nausea and vomiting (P = .01). Overall QoL (global functioning)
      tended to be better (P = .08) after CAI/RT. CONCLUSIONS: Over a period of 24
      months, CAI/RT improved QoL compared with observation alone in patients with
      resected pancreatic and periampullary cancer. This beneficial effect of CAI/RT
      was most prominent in the latter half of the follow-up.

PMID- 20029976
TI  - Gene expression signatures in breast cancer distinguish phenotype
      characteristics, histologic subtypes, and tumor invasiveness.
AB  - BACKGROUND: The development of reliable gene expression profiling technology is
      having an increasing impact on the understanding of breast cancer biology.
      METHODS: In this study, microarray analysis was performed to establish gene
      signatures for different breast cancer phenotypes, to determine differentially
      expressed gene sequences at different stages of the disease, and to identify
      sequences with biologic significance for tumor progression. Samples were taken
      from patients before their treatment. After microarray analysis, the expression
      level of 153 selected genes was studied by real-time quantitative polymerase
      chain reaction analysis. RESULTS: Several gene sequences were expressed
      differentially in tumor samples versus control samples and also were associated
      with different breast cancer phenotypes, estrogen receptor status, tumor
      histology, and grade of tumor differentiation. In lymph node-negative tumors were
      identified a set of genes related to tumor differentiation grade. CONCLUSIONS:
      Several differentially expressed gene sequences were identified at different
      stages of breast cancer.

PMID- 20029975
TI  - Quantitative assessment of cardiorespiratory fitness, skeletal muscle function,
      and body composition in adults with primary malignant glioma.
AB  - BACKGROUND: The study was undertaken to evaluate cardiorespiratory fitness,
      skeletal muscle function, and body composition of patients with newly diagnosed
      and untreated, postsurgical primary malignant glioma. METHODS: By using a cross
      sectional design, patients with clinically stable (10 +/- 7 days postsurgery)
      high-grade glioma (HGG; n = 25) or low-grade glioma (LGG; n = 10) were studied.
      Participants performed a cardiopulmonary exercise test (CPET) with expired gas
      analysis to assess cardiorespiratory fitness (peak oxygen consumption, VO2peak).
      Other physiological outcomes included skeletal muscle cross-sectional area (CSA;
      magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer),
      and body composition (air displacement plethysmography). Quality of life was
      assessed with the Functional Assessment of Cancer Therapy-Brain scale. RESULTS:
      CPET was a feasible and safe procedure to assess VO2peak, with no serious adverse
      events. VO2peak indexed to total body weight and lean body mass (LBM) for both
      groups was 13.0 mL x weight x min(-1) and 19 mL x LBM x min(-1), the equivalent
      to 59% and 38% below age- and sex-predicted normative values, respectively.
      Skeletal muscle strength and mid-thigh CSA were lower in HGG relative to LGG
      patients (83 vs 125 Nm, P = .025; 94 vs 119 cm2, P = .171, respectively).
      Skeletal muscle isokinetic strength, CSA, and body composition outcomes predicted
      VO2peak (r = -0.59 to 0.68, P < .05). CONCLUSIONS: Postsurgical glioma patients
      have markedly reduced cardiorespiratory fitness, isokinetic strength, and CSA.
      Prospective studies are now required to determine whether such abnormalities
      influence treatment toxicity and clinical outcome as well as to test the effect
      of appropriately selected interventions to prevent and/or mitigate dysfunction.

PMID- 20029977
TI  - Pack-years of cigarette smoking as a prognostic factor in patients with stage
      IIIB/IV nonsmall cell lung cancer.
AB  - BACKGROUND: This study was undertaken to characterize the relation between the
      survival of patients with stage IIIB/IV nonsmall cell lung cancer (NSCLC) and
      pack-years of cigarette smoking (graded according to the American Joint Committee
      on Cancer staging system). METHODS: Data were analyzed from patients with stage
      IIIB/IV NSCLC who had completed a prospective smoking questionnaire. The impact
      of pack-years of cigarette smoking, age, sex, Karnofsky performance status (KPS),
      and the presence of weight loss >5% was evaluated on overall survival using
      univariate and multivariate analyses. RESULTS: Smoking history and clinical data
      were available for 2010 patients with stage IIIB/IV NSCLC (1004 women and 1006
      men). Approximately 70% of patients (1409 patients) had smoked >15 pack-years,
      13% (270) were former and current smokers who had smoked < or = 15 pack-years,
      and 16% (331) were never-smokers (<100 lifetime cigarettes). Never-smokers had a
      longer median survival compared with former or current smokers (17.8 months vs
      11.3 months; log-rank P < .001). Among smokers, patients with a < or = 15 pack
      year history of smoking had a longer median survival than patients who had smoked
      >15 pack-years (14.6 months vs 10.8 months; log-rank P = .03). As the number of
      pack-years increased, the median overall survival decreased (log-rank P < .001).
      Multivariate analysis indicated that a history of smoking was an independent
      prognostic factor (hazard ratio, 1.36; P < .001). CONCLUSIONS: More cigarette
      smoking, measured in pack-years, was associated with decreased survival after a
      diagnosis of stage IIIB/IV NSCLC. Trials assessing survival in patients with
      stage IIIB/IV NSCLC should report a detailed cigarette smoking history for all
      patients.

PMID- 20029978
TI  - Alpha-synuclein overexpression in mice alters synaptic communication in the
      corticostriatal pathway.
AB  - alpha-Synuclein (alpha-Syn) is a presynaptic protein implicated in Parkinson's
      disease (PD). Mice overexpressing human wildtype (WT) alpha-Syn under the Thy1
      promoter show high levels of alpha-Syn in cortical and subcortical regions,
      exhibit progressive sensorimotor anomalies, as well as non-motor abnormalities
      and are considered models of pre-manifest PD as there is little evidence of early
      loss of dopaminergic (DA) neurons. We used whole-cell patch clamp recordings from
      visually identified striatal medium-sized spiny neurons (MSSNs) in slices from
      alpha-Syn and WT littermate control mice at 35, 90 and 300 days of age to examine
      corticostriatal synaptic function. MSSNs displayed significant decreases in the
      frequency of spontaneous excitatory postsynaptic currents (EPSCs) in alpha-Syn
      mice at all ages. This difference persisted in the presence of tetrodotoxin,
      indicating it was independent of action potentials. Stimulation thresholds for
      evoking EPSCs were significantly higher and responses were smaller in alpha-Syn
      mice. These data suggest a decrease in neurotransmitter release at the
      corticostriatal synapse. At 90 days the frequency of spontaneous GABA(A) receptor
      mediated synaptic currents was decreased in MSSNs but increased in cortical
      pyramidal neurons. These observations indicate that high levels of expression of
      alpha-Syn alter corticostriatal synaptic function early and they provide evidence
      for early synaptic dysfunction in a pre-manifest model of PD. Of importance,
      these changes are opposite to those found in DA-depletion models, suggesting that
      before degeneration of DA neurons in the substantia nigra synaptic adaptations
      occur at the corticostriatal synapse that may initiate subtle preclinical
      manifestations.

PMID- 20029979
TI  - Behavioral and electrophysiological effects of 5-HT in globus pallidus of 6
      hydroxydopamine lesioned rats.
AB  - Anatomical studies have shown that the globus pallidus receives abundant 5
      hydroxytryptamine (5-HT) innervations from raphe nuclei. 5-HT may occupy an
      important position in the modulation of motor function through its affect on the
      activity of globus pallidus. In the present study, intrapallidal microinjection
      of 5-HT (0.1 mM) alone did not induce any motor behavior or postural asymmetry in
      the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. However, when infused
      concomitantly with a low dose of 3, 4-dihydroxyphenylalanine (L-DOPA, 3 mg/kg
      i.p.), which itself can induce modest contralateral rotational behavior, 5-HT
      significantly potentiated the number of contralateral rotations. To elucidate the
      cellular mechanism, in vivo extracellular recordings were performed to examine
      the effects of 5-HT on globus pallidus neurons. In normal rats, the predominant
      effect of micropressure ejection of 5-HT on pallidal neurons was excitation. In 6
      OHDA-lesioned rats, although 5-HT increased the firing rate in most pallidal
      neurons, 5-HT-induced inhibitory effects was stronger than that on the unlesioned
      side as well as normal rats. Furthermore, 5-HT(1B) receptors are mainly involved
      in 5-HT-induced excitation while 5-HT(1A) receptors are involved in 5-HT-induced
      inhibition. The results suggest that 5-HT may potentiate the antiparkinsonian
      effect of L-DOPA through modulating the activity of globus pallidus.

PMID- 20029980
TI  - Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric
      assay kits and laboratory standardization using Certified Reference Material 457
      (CRM-457).
AB  - BACKGROUND: Serum thyroglobulin (Tg) is essential in the follow-up of patients
      with differentiated thyroid carcinoma (DTC). However, interchangeability and
      standardization between Tg assays have not yet been achieved, even with the
      development of an international Tg standard (Certified Reference Material 457
      [CRM-457]). METHODS: Serum Tg from 30 DTC patients and serially diluted CRM-457
      were measured using 3 different immunoradiometric assays (IRMA-1, IRMA-2, IRMA
      3). The intraclass correlation coefficient (ICC) method was used to describe the
      concordance of each IRMA to CRM-457. RESULTS: The serum Tg measured by 3
      different IRMAs correlated well (r > .85, p < .0001), but clinically relevant
      discrepancies were found in 13.3% of patients. IRMA-3, which claims to be
      standardized to CRM-457, showed the best ICC (p(1) = .98) for the CRM-457.
      CONCLUSIONS: Hospitals caring for patients with DTC should either set their own
      cutoffs for IRMAs for Tg based on their patient pools, or adopt IRMAs
      standardized to CRM-457 and calibrate their laboratory using CRM-457.

PMID- 20029981
TI  - Interpretation of treatment outcome in the clinically node-negative neck in
      primary parotid carcinoma: a systematic review of the literature.
AB  - BACKGROUND: Critical evaluation of outcome of primary parotid carcinoma treatment
      is limited by pathologic diversity and low incidence numbers. Scientific evidence
      for the optimal management of the N0-neck is scarce and was, therefore,
      investigated in a systematic literature review. METHODS: The articles included
      were published in English between 1997 and 2007 and describe populations with the
      definitive pathology, staging, and treatment. Of 1104 articles, 19 were selected,
      describing 2703 patients. RESULTS: Of eligible populations, 83% were clinically
      N0. Pathology reporting of elective lymph node dissection (ELND) had limitations,
      but 23% showed occult metastases. Regional recurrence occurred in 5% of patients.
      CONCLUSION: The discrepancy between the relatively high percentage of occult
      metastases and reported low regional recurrence rates may indicate the efficacy
      of treatment, being either ELND or radiotherapy of the neck. Pooling,
      standardized collection, and reporting of data are essential in comparing
      outcomes in populations to determine optimal treatment.

PMID- 20029982
TI  - Intrinsic differences in cisplatin sensitivity of head and neck cancer cell
      lines: Correlation to lysosomal pH.
AB  - BACKGROUND: Cisplatin treatment is beneficial for approximately 20% of patients
      with head and neck squamous cell carcinoma (HNSCC). Tools to predict the clinical
      outcome and evaluate intrinsic cisplatin sensitivity are, therefore, required.
      METHODS: Cisplatin sensitivity, lysosomal pH, and cell death pathway was studied
      in 5 HNSCC lines and compared with normal oral keratinocytes. RESULTS: We
      identified a linear relationship between lysosomal pH and cisplatin sensitivity.
      Reduced lysosomal acidification was correlated to decreased expression of the
      V(0)V(1)-ATPase B2 subunit, which is part of the lysosomal acidifying complex.
      Cisplatin caused apoptosis accompanied by lysosomal membrane permeabilization,
      and inhibition of lysosomal proteases (cathepsins) partly prevented cell death.
      CONCLUSION: Cisplatin-induced apoptosis of HNSCC is more efficient in cell lines
      with low lysosomal pH and is mediated by the release of lysosomal content.
      Lysosomal pH and expression of V(0)V(1)-ATPase subunits are possible future
      markers of intrinsic cisplatin sensitivity.

PMID- 20029983
TI  - Narrow-band imaging for detecting early recurrent nasopharyngeal carcinoma.
AB  - BACKGROUND: Detection of early recurrent nasopharyngeal carcinoma (NPC) is
      clinically challenging. Narrow-band imaging (NBI) is powerful in detecting early
      superficial lesions in the head and neck, although the utility of NBI in
      detecting nasopharyngeal cancer is still unknown. METHODS AND RESULTS: We
      describe a case of a 51-year-old man with early recurrent NPC detected in
      subclinical stage by NBI coupled with conventional endoscopy. MRI revealed no
      obvious bulging or inward invasion over the nasopharynx. Because of superficial,
      localized recurrence, we performed laser nasopharyngectomy and his postoperation
      course was uneventful. CONCLUSIONS: We demonstrated that postirradiated NPC in a
      patient with early recurrence was successfully detected by NBI coupled with
      conventional endoscopy. NBI endoscopy is a simple, convenient, and reliable tool,
      and adds additional value to detect local recurrence in the early phase. It may
      serve as an ideal tool in posttreatment surveillance in a patient with NPC.

PMID- 20029984
TI  - Incidence and circumstances of cervical hematoma complicating thyroidectomy and
      its relationship to postoperative vomiting.
AB  - BACKGROUND: Cervical hematoma is hardly a predictable complication of thyroid
      surgery. Postoperative vomiting has been reported as a likely risk factor.
      METHODS: Five hundred sixty-two patients undergoing thyroidectomy were
      prospectively enrolled in the study and divided into 2 groups. Patients in group
      A received ondansetron to prevent postoperative vomiting. In group B, patients
      with low vomiting risk received ondansetron whereas patients at high risk
      received ondansetron plus dexamethasone. Postoperative outcomes of the groups
      were analyzed and compared. RESULTS: Cervical hematomas developed in 3 patients
      (0.53%): 2 in group A and 1 in group B. All hematomas occurred after 6 hours. The
      incidence of postoperative vomiting was 11.4% in group A and 6.4% in group B (p =
      .04). CONCLUSION: Careful hemostasis remains of prime importance in preventing
      cervical hematoma. Postoperative vomiting has not been confirmed by this study as
      a risk factor for the development of hematoma. Ambulatory thyroid surgery is not
      advisable.

PMID- 20029985
TI  - Prognostic value of MAGE-A and NY-ESO-1 expression in pharyngeal cancer.
AB  - BACKGROUND: The prognostic value of cancer testis antigens in pharyngeal cancer
      is understudied. METHODS: We recruited 90 patients who were treated for
      pharyngeal cancer. Monoclonal antibodies 57B and B9.8.1.1 were used for detection
      of MAGE-A and NY-ESO-1 genes. RESULTS: MAGE-A and NY-ESO-1 gene products were
      detectable in 70.0% and 33.3% of pharyngeal tumors, respectively. No correlation
      was established between MAGE-A and NY-ESO-1 expression and TNM staging at
      presentation. Survival analysis showed a trend toward a shorter 5-year disease
      free survival in the group of patients with MAGE-A-positive tumors (log-rank
      test, p = .122). In contrast, a trend toward a prolonged 5-year disease-free
      survival was observed in the group of patients with NY-ESO-1-positive tumors (log
      rank test, p = .219). CONCLUSION: In a large population of patients with
      pharyngeal cancer and available 5-year survival data, prognosis tended to be
      poorer with MAGE-A expression and better with NY-ESO-1 expression, but the
      correlations did not reach statistical significance.

PMID- 20029987
TI  - Role of radiotherapy in early glottic carcinoma.
AB  - BACKGROUND: Early glottic carcinoma has a high local control prospect with
      radiotherapy. This review evaluates a single center's experience. METHODS: All
      patients from 1967 to 2006 diagnosed with Tis/T1/T2/N0 early glottic carcinoma
      treated definitively with radiotherapy at Prince of Wales Hospital were reviewed.
      Local control and cancer-specific survival (CSS) rates were primary endpoints,
      and the impact of various factors on these outcomes was statistically analyzed.
      RESULTS: This review of 522 patients includes 24 with Tis, 356 with T1, and 142
      with T2. Ultimate local control rates were as follows: Tis 87.5%, T1 94.7%, and
      T2 84.5%. Multivariate analysis found fitness for surgery, no involvement of
      anterior commissure, normal cord movement, and radiotherapy dose >60 Gy
      significant for local control. Fitness for surgery, no involvement of the
      anterior commissure, normal cord movement, and no ventricular involvement were
      significant prognostic factors for CSS. CONCLUSION: Definitive radiotherapy for
      early glottic carcinoma provides high local control rates, with the option of
      surgical salvage to achieve ultimate local control.

PMID- 20029986
TI  - HPV status-independent association of alcohol and tobacco exposure or prior
      radiation therapy with promoter methylation of FUSSEL18, EBF3, IRX1, and SEPT9,
      but not SLC5A8, in head and neck squamous cell carcinomas.
AB  - Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with
      more than half a million people being diagnosed with the disease annually. Within
      the last 2 decades, the human papillomavirus (HPV) has been found to be
      associated with this malignancy. More recently, HPV-infected HNSCC has been found
      to exhibit higher levels of global DNA methylation. In a recent study, we
      identified five tumor suppressive genes (IRX1, EBF3, SLC5A8, SEPT9, and FUSSEL18)
      as frequently methylated in HNSCC biopsies using a global methylation analysis
      via restriction landmark genomic scanning. In this study, we verify these genes
      as valid methylation markers in two separate sets of HNSCC specimens. By using
      the available clinical information linked to the patient specimens, we found a
      strong association between promoter methylation of FUSSEL18, IRX1, and EBF3 and
      prior radiation therapy (P < 0.0001) irrespective of HPV status. Also, promoter
      methylation of FUSSEL18 and SEPTIN9 was found to correlate significantly with
      exposure to alcohol and tobacco (P = 0.021). Importantly, in this study, we
      preliminarily show a trend between HPV16 positivity and specific target gene
      hypermethylation of IRX1, EBF3, SLC5A8, and SEPT9. If replicated in a larger
      study, the HPV status may be a patient selection biomarker when determining the
      most efficacious treatment modality for these different subsets of patients
      (e.g., inclusion or exclusion of epigenetic therapies). Equally notable and
      independent of HPV status, hypermethylation of the promoters of a subset of these
      genes in recurrences especially in the setting of prior radiation or in the
      setting of alcohol and tobacco use might help guide adjunctive inclusion or
      exclusion or epigenetic therapy.

PMID- 20029988
TI  - Retinal vascular changes after glial disruption in rats.
AB  - Glial dysfunction is found in a number of retinal vascular diseases but its link
      with blood-retinal barrier (BRB) breakdown remains poorly understood. The present
      study tested the hypothesis that glial dysfunction is a major contributor to the
      BRB breakdown that is a hallmark of retinal vascular diseases. We investigated
      the specificity of the purportedly selective glial toxin, DL-alpha-aminoadipic
      acid (DL-alpha-AAA) on different types of ocular cells in vitro and then tested
      the effect of glial disruption on retinal vasculature after intraocular injection
      of DL-alpha-AAA or siRNA targeting glutamine synthetase (GS) in rats. DL-alpha
      AAA was toxic to astrocytes and Muller cells but not to other types of BRB
      related cells in vitro. Subretinal injection of DL-alpha-AAA disrupted retinal
      glial cells, induced vascular telangiectasis and increased vascular permeability
      from 4 days to over 2 months post-injection. Vascular changes induced by DL-alpha
      AAA were observed predominantly in regions of glial disruption, as reflected by
      reduced expression of GS and increased expression of glial fibrillary acidic
      protein and vimentin. Confocal microscopy showed changes in all three layers of
      the retinal vasculature, which co-localised with areas of Muller cell disruption.
      Double labeling immunohistochemistry revealed that retinal glial disruption after
      DL-alpha-AAA injection was accompanied by increased expression of vascular
      endothelial growth factor and reduced expression of the tight junction protein
      claudin-5. Intravitreal injection of GS siRNA induced similar changes in Muller
      cells and BRB breakdown. Our data are consistent with the hypothesis that glial
      dysfunction is a primary contributor to the BRB breakdown in retinal vascular
      diseases.

PMID- 20029989
TI  - A young woman with episodic angioedema, papilledema, and eosinophilia.

PMID- 20029990
TI  - Progressive multifocal leukencephalopathy and cerebral toxoplasmosis in a patient
      with CLL.

PMID- 20029991
TI  - The value of monitoring minimal residual disease in the patients with donor
      lymphocyte infusion as intervention of relapsed/refractory acute lymphoblastic
      leukemia after allogeneic hematopoietic stem cell transplantation.

PMID- 20029992
TI  - Coexistence of primary AL amyloidosis and POEMS syndrome: efficacy of melphalan
      dexamethasone and role of biochemical markers in monitoring the diseases course.

PMID- 20029993
TI  - Letter in response to: "Pulmonary thrombi are not detected by 3D magnetic
      resonance angiography in adults with sickle cell anemia and an elevated
      triscuspid regurgitant jet velocity".

PMID- 20029996
TI  - Knockdown of IGF-binding protein 7 inhibits transformation of the endometrial
      gland in an in vitro model.
AB  - Uterine endometrial glands and their secretory products are critical for the
      implantation and survival of the peri-implantation embryo, and for the
      establishment of uterine receptivity. We previously reported that insulin-like
      growth factor binding protein 7 (IGFBP7) is abundantly expressed in uterine
      glandular epithelial cells during the secretory phase of the menstrual cycle. In
      the present study, we used a cultured glandular epithelial cell line of human
      (EM1) to investigate the significance of IGFBP7 in the function of endometrial
      glands. EM1 cells formed a mesh-like structure on Matrigel, which was accompanied
      by elevated levels of intracellular cyclic AMP. However, these morphological
      changes were blocked by treatment with protein kinase A (PKA) inhibitor (H89).
      IGFBP7 knockdown using specific short interference RNA (siRNA) inhibited the
      formation of the mesh-like structure on Matrigel. Cyclic AMP analogs, dibutyryl
      cAMP, and N(6)-phenyl-cAMP induced the expression of leukemia inhibitory factor
      (LIF) which is essential for the onset of implantation. Enhanced LIF expression
      was suppressed by IGFBP7 siRNA treatment. Western blot analysis revealed that
      IGFBP7 knockdown results in the aberrant, constitutive expression of the MAPK
      signaling pathway. These results suggest that IGFBP7 regulates morphological
      changes of glandular cells by interfering with the normal PKA and MAPK signaling
      pathways that are associated with the transformation and/or differentiation of
      endometrial glands.

PMID- 20029997
TI  - A continuous spectrophotometric assay for determination of the aureusidin
      synthase activity of tyrosinase.
AB  - INTRODUCTION: Aurones (aureusidin glycosides) are plant flavonoids that provide
      yellow colour to the flowers of some ornamental plants. In this study we analyse
      the capacity of tyrosinase to catalyse the synthesis of aureusidin by tyrosinase
      from the chalcone THC (2',4',6',4-tetrahydroxychalcone). OBJECTIVE: To develop a
      simple continuous spectrophotometric assay for the analysis of the
      spectrophotometric and kinetic characteristics of THC oxidation by tyrosinase.
      METHODOLOGY: THC oxidation was routinely assayed by measuring the increase in
      absorbance at 415 nm vs. reaction time. RESULTS: According to the mechanism
      proposed for tyrosinase, the enzymatic reaction involves the o-hydroxylation of
      the monophenol THC to the o-diphenol (PHC, 2',4',6',3,4 - pentahydroxychalcone),
      which is then oxidised to the corresponding o-quinone in a second enzymatic step.
      This product is highly unstable and thus undergoes a series of fast chemical
      reactions to produce aureusidin. In these experimental conditions, the optimum pH
      for THC oxidation is 4.5. The progress curves obtained for THC oxidation showed
      the appearance of a lag period. The following kinetic parameters were also
      determined: K(m )= 0.12 mM, V(m )= 13 microM/min, V(m)/K(m )= 0.11/min.
      CONCLUSION: This method has made it possible to analyse the spectrophotometric
      and kinetic characteristics of THC by tyrosinase. This procedure has the
      advantages of a short analysis time, straightforward measurement techniques and
      reproducibility. In addition, it also allows the study of tyrosinase inhibitors,
      such as tropolone.

PMID- 20029995
TI  - Neurogenin1 effectively reprograms cultured chick retinal pigment epithelial
      cells to differentiate toward photoreceptors.
AB  - Photoreceptors are highly specialized sensory neurons in the retina, and their
      degeneration results in blindness. Replacement with developing photoreceptor
      cells promises to be an effective therapy, but it requires a supply of new
      photoreceptors, because the neural retina in human eyes lacks regeneration
      capability. We report efficient generation of differentiating, photoreceptor-like
      neurons from chick retinal pigment epithelial (RPE) cells propagated in culture
      through reprogramming with neurogenin1 (ngn1). In reprogrammed culture, a large
      number of the cells (85.0% +/- 5.9%) began to differentiate toward
      photoreceptors. Reprogrammed cells expressed transcription factors that set in
      motion photoreceptor differentiation, including Crx, Nr2E3, NeuroD, and RXRgamma,
      and phototransduction pathway components, including transducin, cGMP-gated
      channel, and red opsin of cone photoreceptors (equivalent to rhodopsin of rod
      photoreceptors). They developed inner segments rich in mitochondria. Furthermore,
      they responded to light by decreasing their cellular free calcium (Ca(2+)) levels
      and responded to 9-cis-retinal by increasing their Ca(2+) levels after
      photobleaching, hallmarks of photoreceptor physiology. The high efficiency and
      the advanced photoreceptor differentiation indicate ngn1 as a gene of choice to
      reprogram RPE progeny cells to differentiate into photoreceptor neurons in future
      cell replacement studies.

PMID- 20029998
TI  - Countenancing history: Mary Wollstonecraft, Samuel Stanhope Smith, and
      Enlightenment racial science.

PMID- 20029999
TI  - "To laugh at a penniless man rather than a prostitute": the unofficial worlds of
      prostitution in late Qing and early republican South China.

PMID- 20030000
TI  - "Wish you were here": exporting England in James Grainger's The Sugarcane.

PMID- 20030001
TI  - Measuring social capital: culture as an explanation of Italy's economic dualism.

PMID- 20030002
TI  - Tristram Shandy and the theater of the mechanical mother.

PMID- 20030003
TI  - Daniel Defoe's Colonel Jack, grateful slaves, and racial difference.

PMID- 20030004
TI  - A less common cause of diarrhoea.

PMID- 20030005
TI  - "Counterfeit Egyptians" and imagined borders: Jonson's The Gypsies Metamorphosed.

PMID- 20030006
TI  - Feeding on the seed of the woman: Dorothy Leigh and the figure of maternal
      dissent.

PMID- 20030008
TI  - Oysters and rye bread: polarising living standards in Flanders, 1800-1860.

PMID- 20030009
TI  - Rational investment behaviour and seasonality in early modern grain prices.

PMID- 20030010
TI  - "To pursue the stream to its fountain": race, inequality, and the post-colonial
      exchange of knowledge across the Atlantic.

PMID- 20030011
TI  - [An Estonian Volksgemeinschaft? The Estonian Joint Help organization in 1941
      1944].

PMID- 20030012
TI  - [Unruly women: Finnish missionaries and authority in early-20th-century Japan].

PMID- 20030013
TI  - Violent repression or modern strategies of crowd management: soldiers as riot
      police in France and Germany, 1890-1914.

PMID- 20030014
TI  - The Hopital general, the Parisian elites and crown social policy during the reign
      of Louis XIV.

PMID- 20030016
TI  - [Places for the everyday - places of piety: observations on the city/spaces of
      the Viennese high aristocracy at the end of the 17th century].

PMID- 20030017
TI  - [Mass relief projects in the early Nazi era: focusing on winter relief work].

PMID- 20030018
TI  - Journal of Health Politics, Policy and Law. Editor's note.

PMID- 20030019
TI  - [Joking about sex and the body in late imperial China: an analysis based on the
      jest book Xiaolin Guangji].

PMID- 20030020
TI  - The publication of sources on the history of the 1932-1933 famine-genocide:
      history, current state, and prospects.

PMID- 20030022
TI  - Aliskiren/valsartan combination for the treatment of cardiovascular and renal
      diseases.
AB  - Chronic activation of the renin-angiotensin-aldosterone system (RAAS) plays a key
      role in the development of hypertension, and cardiac and renal diseases. RAAS
      inhibitors, such as angiotensin-converting enzyme (ACE) inhibitors and
      angiotensin receptor blockers (ARBs), improve cardiovascular and renal outcomes.
      However, studies have shown that residual morbidity and mortality remains high,
      despite current optimal treatment. More comprehensive control of the RAAS might
      provide additional reductions in morbidity and mortality. Direct renin inhibitors
      offer the potential for enhanced RAAS control as they target the system at the
      point of activation, thereby reducing plasma renin activity (PRA); by contrast,
      ARBs and ACE inhibitors increase PRA. Elevated PRA is independently associated
      with cardiovascular morbidity and mortality. A single-pill combination of the
      direct renin inhibitor, aliskiren, and the ARB, valsartan, at once-daily doses of
      150/160 mg and 300/320 mg, has recently been approved by the US FDA for the
      treatment of hypertension in patients not adequately controlled on aliskiren or
      ARB monotherapy, and as initial therapy in patients likely to need multiple drugs
      to achieve their blood pressure goals. This article examines the efficacy, safety
      and tolerability of aliskiren/valsartan combination therapy, and considers the
      evidence for the potential organ-protection benefits of this treatment.

PMID- 20030023
TI  - Current noninvasive imaging techniques for detection of coronary artery disease.
AB  - The development and widespread use of noninvasive imaging techniques have
      contributed to the improvement in evaluation of patients with known or suspected
      coronary artery disease. Stress echocardiography and single-photon computed
      tomography are well-established noninvasive techniques with a proven track record
      for the diagnosis of coronary atherosclerosis. These modalities are generally
      widely available and provide a relatively high sensitivity and specificity along
      with an incremental value over clinical risk factors for detection of coronary
      artery disease. PET has a high diagnostic performance but continues to have
      limited clinical use because of the high expense of the dedicated equipment and
      difficulties in obtaining adequate radionuclides. Cardiac MRI and multislice
      computed tomography constitute the most recent addition to the cardiac imaging
      armamentarium. Cardiac MRI offers a comprehensive cardiac evaluation, which
      includes wall-motion analysis, myocardial tissue morphology, rest and stress
      first-pass myocardial perfusion, as well as ventricular systolic function.
      Cardiac computed tomography allows coronary calcium scanning along with
      noninvasive anatomic assessment of the coronary tree. It can be combined with
      functional imaging to provide a complete evaluation of the presence and
      physiological significance of the atherosclerotic coronary disease. No single
      imaging modality has been proven to be superior overall. Available tests all have
      advantages and drawbacks, and none can be considered suitable for all patients.
      The choice of the imaging method should be tailored to each person based on the
      clinical judgment of the a priori risk of cardiac event, clinical history and
      local expertise.

PMID- 20030024
TI  - Echocardiographic strain imaging and its use in the clinical setting.
AB  - The use of echocardiography has grown tremendously over the past several years.
      It is used routinely for diagnosis, prognosis and monitoring changes of cardiac
      function in coronary artery disease, heart failure, pulmonary hypertension,
      arrhythmias, pericardial disease and valvular disease, as well as congenital
      conditions. In recent years, the advancing technology used to evaluate the heart
      by ultrasound has allowed physicians to understand the mechanics of the heart
      muscle and the contribution of abnormalities in myocardial movement to heart
      disease. This review will discuss novel echocardiographic strain imaging
      techniques, placing them in the context of myocardial mechanics and describing
      current and future applications.

PMID- 20030025
TI  - Transcatheter aortic valve implantation: role of multimodality cardiac imaging.
AB  - Current evidence based on more than 8000 high-risk patients with severe aortic
      stenosis has demonstrated that transcatheter aortic valve implantation (TAVI) is
      a feasible alternative to surgical aortic valve replacement in selected patients.
      Despite current promising results on hemodynamic and clinical improvements, there
      are several unresolved safety issues, such as the frequency of vascular
      complications, postprocedural paravalvular leak, atrioventricular heart block and
      stroke. Multimodality cardiac imaging may help to minimize these complications
      and may play a central role before (optimizing patient selection, selection of
      appropriate prosthesis size and anticipating the procedural approach), during and
      after TAVI (evaluating the immediate and long-term procedural results). This
      article reviews the state-of-the-art TAVI procedures and the role that
      multimodality cardiac imaging plays before, during and after TAVI.

PMID- 20030026
TI  - Comparison of porcelain veneers and crowns for resolving esthetic problems: two
      case reports.

PMID- 20030027
TI  - Multilocus variable-number tandem repeat analysis as a molecular tool for
      subtyping and phylogenetic analysis of bacterial pathogens.

PMID- 20030028
TI  - Clinical implication of endothelial progenitor cells.
AB  - The exact origin and functional definition of endothelial progenitor cells (EPCs)
      remains rather controversial, but many authors agree that the main feature of
      EPCs is the ability to directly participate in vessel growth by differentiation
      into endothelial cells in vivo. The majority of these cells originate from the
      hematopoietic stem cells of the bone marrow and, under specific signals,
      differentiate and shift into the systemic circulation, contributing to the
      neoangiogenic process and repair of the damaged endothelial monolayer. Recently,
      it has been demonstrated that the number and function of EPCs is positively
      linked with an improved endothelial function or regeneration but inversely
      correlated with cardiovascular risk factors: a reduced number of EPCs is an
      independent predictor of morbidity and mortality of cardiovascular diseases and
      of atherosclerotic disease progression. Owing to their role in endogenous
      maintenance and repair of damaged endothelium, EPCs have been examined for
      therapeutic potential in ischemic diseases and there are evidence-based
      perspectives regarding their use for vascular regenerative medicine.

PMID- 20030029
TI  - Who is responsible for the care of patients treated with warfarin therapy?
      Comment.

PMID- 20030030
TI  - Adverse outcomes of labour in public and private hospitals in Australia. Comment.

PMID- 20030031
TI  - Assessment of hospital performance: the need to complete the "hat trick".

PMID- 20030032
TI  - Does every question deserve a randomized controlled trial?

PMID- 20030033
TI  - Is laparoscopic total gastrectomy the right operation?

PMID- 20030034
TI  - Possibility of sepsis prevention with common genotype.

PMID- 20030035
TI  - Slimming down for safer surgery.

PMID- 20030036
TI  - Getting old shouldn't be an emergency.

PMID- 20030037
TI  - Sutureless thyroidectomy- technological advance or toy?

PMID- 20030038
TI  - [Effect of clarithromycin on the expressions of cyclooxygenase-2 and nuclear
      factor-kappa B in nasal polyps in vitro].
AB  - OBJECTIVE: To detect the expression and correlation of cyclooxygenase-2 (COX-2)
      and nuclear factor-kappa B (NF-kappaB) in nasal polyps co-cultured with
      clarithromycin, and to investigate their roles in CRS pathogenesis. METHOD: Nasal
      polyps from 11 patients with chronic rhinosinusitis (CRS) were cultured for 24
      hours with different doses of clarithromycin (0, 10(-6), 10(-5), 10(-4) mol/L).
      Western blot and real time fluorescence quantitative PCR were performed to detect
      the expressions of COX-2 and NF-kappaB subunits. RESULT: The expression levels of
      COX-2, NF-kappaBp50 and NF-kappaBp65 were most high in control groups (0 mol/L
      clarithromycin). The expressions of COX-2, NF-kappaBp50 and NF-kappaBp65 were
      dose-dependently attenuated as the concentrations of clarithromycin increased.
      Significantly positive correlation between RNA expressions of COX-2 and NF-kappaB
      subunits in each CRS group was confirmed by Pearson correlation treatment
      (P<0.05). CONCLUSION: The increased expression of COX-2 is involved in the
      inflammation in CRS. It indicate that clarithromycin may play an anti
      inflammatory effect on CRS by decreasing the synthesis of COX-2 through blocking
      NF-kappaB pathway.

PMID- 20030039
TI  - [A computational fluid dynamics study of inner flow through nasal cavity with
      unilateral hypertrophic inferior turbinate].
AB  - OBJECTIVE: To investigate the anatomical influence of the hypertrophic inferior
      turbinate on computational fluid dynamics (CFD) model of unilateral hypertrophic
      inferior turbinate nasal cavity, and to analyze the bilateral detailed nasal
      airflow simulations under both inspiratory and expiratory phases in CFD model.
      METHOD: One male volunteer troubled with unilateral hypertrophic inferior
      turbinate accepted CT scan. CFD model was built by CT scans through Simplant 10.0
      and ANSYS ICEM. Fluent 6.3.26 simulated the airflow of both nasal cavity in
      breathing rates 200 ml/s. RESULT: 1) In infraturbinal region, the cross-section
      area (CSA) of the nasal cavity with hypertrophic inferior turbinate was smaller
      than that in healthy side and the average area difference between two sides was
      1.62 cm2. 2) In both inspiration and expiration phases, the hypertrophic
      infraturbinal produced a markable reduction in intranasal pressures drop along
      the full length of the infraturbinal region. The volumetric flow rate in the
      hypertrophic infraturbinal side was 50 ml/s, which equalled to one third of that
      in healthy side; Mean air speed in the anterior valve region was estimated to be
      0.57 m/s at hypertrophic infraturbinal side and 1.83 m/s at healthy side during
      inspiration; More vortices happened in the hypertrophic infraturbinal side.
      CONCLUSION: The unilateral hypertrophic infraturbinal change the normal anatomy
      and influence the aerodynamic of nasal cavity, which is harmful to the functions
      of human nasal in ventilation, temperature accommodation and olfactory sensation.

PMID- 20030040
TI  - [Analysis of the factors affecting the operational therapeutic efficacy for
      rhinosinusitis].
AB  - OBJECTIVE: To investigate the factors influence in the operational therapeutic
      efficacy for sinusitis. METHOD: Logistic regression analysis was performed for
      sex, age, clinical stage of sinusitis, used nasal decongestant preparation,
      recurrence of sinus surgery, allergic rhinitis, extensive postoperative
      treatments in 210 patients. RESULT: Age, used nasal decongestant preparation,
      recurrence of sinus surgery, allergic rhinitis, extensive postoperative
      treatments were the important factors influenced the operation therapeutic
      efficacy. CONCLUSION: Independent prognostic factors for patients with sinusitis
      after endoscopic sinus surgery are age, used nasal decongestant preparation,
      recurrence of sinus surgery, allergic rhinitis, extensive postoperative
      treatments. What's more, extensive postoperative treatments are one of the
      important factors to improve the operational therapeutic efficacy for chronic
      rhinosinusitis.

PMID- 20030041
TI  - [Symptomatic characteristics of chronic rhinosinusitis patients and symptom
      specific outcomes after endoscopic sinus surgery].
AB  - OBJECTIVE: To explore the symptomatic characteristics of chronic rhinosinusitis
      patients and the report symptom-based outcomes after endoscopic sinus surgery.
      METHOD: One hundred and nineteen chronic rhinosinusitis patients underwent
      endoscopic sinus surgery, including 52 patients of chronic rhinosinusitis without
      nasal polyps and 67 patients of chronic rhinosinusitis with nasal polyps, were
      enrolled. Patients were asked to evaluate their symptoms before surgery and 12
      months after endoscopic sinus surgery using 10 cm visual analog scale measures.
      RESULT: The most commonly reported symptoms were nasal obstruction, nasal
      discharge, headache, facial pressure and altered sense of smell. Compared with
      patients of chronic rhinosinusitis with nasal polyps, patients of chronic
      rhinosinusitis without nasal polyps reported significantly higher scores of nasal
      discharge, whereas lower scores of altered sense of smell (P<0.01 for both). The
      most disturbing symptom was nasal discharge and altered sense of smell for
      chronic rhinosinusitis patients without and with nasal polyps, respectively.
      After endoscopic sinus surgery, the scores for all studied symptoms were improved
      greatly in both chronic rhinosinusitis with and without nasal polyps groups
      (P<0.01 for all). CONCLUSION: Chronic rhinosinusitis patients with and without
      nasal polyps present different symptomatic characteristics. Endoscopic sinus
      surgery can improve patient-based symptoms significantly. Visual analog scale is
      a simple and powerful tool to evaluate chronic rhinosinusitis symptoms.

PMID- 20030042
TI  - [Clinical analysis on 14 cases with malignant melanoma in nasal cavity and
      sinus].
AB  - OBJECTIVE: To investigate the effect of treatment on malignant melanoma in nasal
      cavity and paranasal sinus. METHOD: Fourteen patients with malignant melanoma in
      nasal cavity and paranasal sinus were retrospectively analyzed from 1995 to 2002,
      including clinical presentation, diagnosis, treatment and follow-up data. RESULT:
      Thirteen patients were followed up, the survival rates of 3 and 5 years were
      42.9% and 21.4% respectively. CONCLUSION: Sinonasal malignant melanoma has an
      aggressive behavior and easy recurrence. Early diagnosis, radical operation and
      postoperative radiotherapy could improve the survival rate.

PMID- 20030043
TI  - [Treatment of nasal malignant tumor with electron beam irradiation after repair
      of nasolabial flap].
AB  - OBJECTIVE: To explore the appropriate reconstructive methods and curative effect
      after nasal skin malignant tumor excision. METHOD: Nasolabial flap was selected
      to cover the nasal defects in 15 cases which nasal tumors were removed. The
      secondary defect of donor site was directly sutured. Electron beam conventional
      radiotherapy (DT40-50 Gy/20-25 times/4-5 weeks) was delivered to the involved
      field after incision sutured out 2-5 days. RESULT: A total of 15 patients with
      nasal tumor were available for follow-up of 6 to 24 months, no tumor recurrence
      occurred, and the repaired tissue were good match with surrounding tissue, good
      nasal contour was obtained with an inconspicuous scar. CONCLUSION: These data
      indicate that the nasolabial flap can be used to repair defects of the nose
      tumors in 15 cases and is surgically convenient. Combination of nasolabial flap
      repairing and postoperative local electron beam irradiation, inhibited the
      recurrence of nose tumor effectively, is an ideal method.

PMID- 20030044
TI  - [Retrospective analysis on three operative methods for curettage of adenoids in
      children].
AB  - OBJECTIVE: To compare the three different approaches in the curettage of adenoid
      hypertrophy: the traditional curettage of adenoids through mouth (group A), the
      adenoidectomy through nose under nasal endoscope (group B), the adenoidectomy
      through both mouth and nose under nasal endoscope (group C). METHOD: Clinical
      data of adenoid hypertrophy patients who had accepted the surgery therapy, were
      retrospectively analyzed; Symptoms of night snore, nasal obstruction, rhinorrhea,
      acouesthesia and the adenoid residue among the patients who had got three
      different surgery, were compared among them. RESULT: Adenoid residue were found
      in six cases of group A. No adenoid residue were found in group B and C .
      Recovery of nasal obstruction and night snore in group C were much better than
      that in group A and B (P<0.01, <0.05). CONCLUSION: The ideal way to cure
      adenoidal hypertrophy is the adenoidectomy done through mouth and nose under
      nasal endoscope.

PMID- 20030045
TI  - [Repairment of laryngeal fistula following electrical burn].
AB  - OBJECTIVE: To explore a method for the repairment of laryngeal fistula following
      electrical burn. METHOD: Sternocleidomastoid myocutaneous flap was applied to
      restore laryngeal fistula following electrical injuries. RESULT: The patient was
      cured with good repairment of cutaneous defect and laryngeal function following
      operation. CONCLUSION: Application of neighboring myocutaneous flap is beneficial
      for the reconstruction of damaged tissue.

PMID- 20030046
TI  - [Expression of thymic stromal lymphopoietin in nasal mucosa of a mouse model with
      allergic rhinitis].
AB  - OBJECTIVE: To investigate the expression of thymic stromal lymphopoietin (TSLP)
      in the nasal mucosa of mouse with allergic rhinitis. METHOD: Twenty wide type
      BALB/c mouse were divided into 2 groups randomly. Two groups were included,
      allergic rhinitis group (group A) and control group (group B). The mouse model of
      allergic rhinitis was established by ovalbumin (OVA) sensitization and challenge.
      The expressions of TSLP in the nasal mucosa was determined by realtime
      quantitative PCR and immunohistochemical method. RESULT: The expression of TSLP
      in the nasal mucosa of group A was significantly higher than that in group B
      (P<0.01). CONCLUSION: TSLP plays a role in the mouse model of allergic rhinitis.

PMID- 20030047
TI  - [Expression and significance of Survivin mRNA in xenotransplanted nasopharyngeal
      carcinoma treated by paclitaxel combined with radiotherapy].
AB  - OBJECTIVE: To investigate the expression and significance of Survivin mRNA in
      xenotransplanted nasopharyngeal carcinoma treated by paclitaxel combined with
      radiotherapy. METHOD: Xenotransplanted nasopharyngeal carcinoma was established
      by CNE-2 cell line, then grouped and treated with paclitaxel, radiotherapy,
      paclitaxel combined with radiotherapy respectively. Xenotransplanted tumor volume
      was measured; tumor specimens were confirmed by routine hemotoxylin-eosin
      staining; apoptosis index was assayed by flow cytometry and Survivin mRNA was
      detected by one step RT-PCR. RESULT: Xenotransplanted tumor growth was
      significantly inhibited by paclitaxel combined with radiotherapy and its
      inhibition rate was 99.3%. Compared to control group, apoptosis index was
      apparently increased in the other three groups (P<0.05), especially in the
      combined therapy group (P<0.05). Survivin mRNA expression was obviously decreased
      in the combined therapy group (P<0.05); whereas there was no difference in its
      expression among the groups of paclitaxel, radiotherapy, and control group
      (P>0.05). CONCLUSION: Paclitaxel combined with radiotherapy can induce
      significant killing effect in xenotransplanted nasopharyngeal carcinoma;
      paclitaxel can enhance the radiosensitivity of xenotransplanted nasopharyngeal
      carcinoma and its mechanism may rely on the down-regulation of Survivin
      expression.

PMID- 20030048
TI  - [Recent advances and prospect on structural biology of beta-mannanase--a review].
AB  - Beta-mannanases (beta-1,4-D-mannanase, EC 3.2.1.78), as a hemicellulose
      hydrolase, are widely distributed in bacteria, fungi, plants and even animals.
      They can randomly hydrolyze the beta-1,4-mannosidic linkages in mannan and
      heteromannan and have great potential in the food/feed, pulp/paper, medicine, oil
      exploitation and detergent industries. Most beta-mannanases often display a
      modular organization and usually contain structurally discrete catalytic and non
      catalytic modules. Catalytic domains of these enzymes share a (beta/alpha)8
      barrel fold, which play important roles in substrate binding and catalysis.
      Carbohydrate binding modules, as the most common non-catalytic modules, fold as
      beta-sandwich and facilitate the targeting of these enzymes to polysaccharide. In
      this review, a brief introduction is given concerning structural characteristics
      and function of these beta-mannanase modules.

PMID- 20030049
TI  - [Swine influenza virus: evolution mechanism and epidemic characterization--a
      review].
AB  - Pigs may play an important role in the evolution and ecology of influenza A
      virus. The tracheal epithelium of pigs contain both SA alpha 2,6 Gal and SA alpha
      2,3 Gal receptors and can be infected with swine, human and avian viruses,
      therefore, pigs have been considered as an intermediate host for the adaptation
      of avian influenza viruses to humans or as mixing vessels for the generation of
      genetically reassortant viruses. Evolution patterns among swine influenza viruses
      including evolution of host adaptation, antigenic drift and genetic reassortment,
      and the latter is the main one. Unlike human influenza viruses, swine viruses
      have different epizootiological patterns in different areas of world, which is
      enzootic and geographic dependence. Currently, three predominant subtypes of
      influenza virus are prevalent in pig populations worldwide: H1N1, H3N2, and H1N2,
      and these include classical swine H1N1, avian-like H1N1, human-like H3N2,
      reassortant H3N2 and various genotype H1N2 viruses. In Europe, North America and
      China, influenza A viruses circulating in pigs are distinct in the genetic
      characteristics and genetic sources. Since 1979, three subtypes, avian-like H1N1,
      reassortant H1N2 and H3N2 viruses, have been co-circulating in European swine.
      Before 1998, classical H1N1 viruses were the exclusive cause of swine influenza
      in North America. However, after that, three triple-reassortant H1N2, H3N2 and
      H1N1 viruses with genes of human, swine and avian virus began to emerge in pigs.
      Genetically, the pandemic viruses emerging in human, so called influenza A (H1N1)
      viruses, contain genes from both Europe and North American SIV lineages. SIV is
      not the same as Europe and the United States in the prevalence and genetic
      background in China, mainly classical swine H1N1 and human-like H3N2 type virus.
      However, in recent years, SIV from Europe and North America have been introduced
      into Chinese pig herds, so more attention should be given on the evolutionary of
      SIV in China. Worldwide, more than 50 cases of SIV infection in human have been
      documented since the 1970s, which indicate that SIV is also an important
      zoonosis, and the potential of SIV as human pandemic virus or genes donator. In
      view of SIV in the importance of ecology, as well as a potential threat to human
      public health, it is recommended to start as soon as possible regular
      surveillance, paying close attention to its prevalence and molecular evolution.
      At the same time, we should establish the surveillance network of the whole
      influenza virus (including human and animal influenza virus) in China,
      ecologically mastering the prevalence and evolution of influenza viruses, which
      is of great significance for the protection of animal health and the prevention
      of human pandemic.

PMID- 20030050
TI  - [Progress on pigment-protein complexes from anoxygenic phototrophic bacteria--a
      review].
AB  - Anoxygenic phototrophic bacteria have evolved highly efficient systems-membrane
      located pigment-protein complexes which can convert sunlight into chemical energy
      that they can use and also benefit other organisms. More and more attentions have
      been paid to pigment-protein complexes of anoxygenic phototrophic bacteria in
      recent years. We summarized the current opinions in the pigment-protein complexes
      from anoxygenic phototrophic bacteria, including their chemical compositions,
      crystal structures and functions, homology of protein sequence. In particular, we
      depicted the novel light-harvesting complexes namely LH3 and LH4. The problems
      and prospects about the pigment-protein complexes have also been addressed in
      this review.

PMID- 20030051
TI  - [Diversity and bioactivities of cultured actinomycete isolated from animal feces
      and Xylocopa dissimilis].
AB  - OBJECTIVE: To study the diversity and bioactivities of cultured actinomycete from
      feces of Ailuropoda melanoleuca, Equus burchelli and Rhizomys sinensis, and
      Xylocopa dissimilis body. METHODS: Fresh feces samples of animals' and Xylocopa
      dissimilis were collected. We used four media to isolate the actinomycete.
      Strains were identified by phylogenetic analysis of 16S rRNA gene sequences.
      Hydrolization and enzyme activities of isolates were examined. RESULTS:
      Actinomycetes (121) from the samples were isolated on four media. Among them 47
      strains belonged to 9 actinomycetes genera. Six known rare genera and one
      possible new genus of actinomyctes from Rhizomys sinensis were identified. Three
      possible new species from other three samples were identified. Some strains could
      hydrolyze chicken feather and cellulose. CONCLUSION: It is considered that the
      coprophilous microorganisms not only have important function on the digestion and
      absorption of animal feed, but also are important resource for development of
      industrial products, including enzyme and bioactive metabolites.

PMID- 20030052
TI  - [Regulation of type III secretion system by Rhl and PQS quorum sensing systems in
      Pseudomonas aeruginosa].
AB  - OBJECTIVE: To investigate the relationship between quorum sensing (QS) and type
      III secretion system (T3SS) in Pseudomonas aeruginosa. METHODS: We constructed
      several gene knockout mutants of QS systems. The promoters of the T3SS genes,
      exoS, exoY, exoT and exsD-pscA-L were cloned and fused upstream of the
      luminescence reporter gene cluster, luxCDABE. The reporter constructs were
      integrated on the chromosome in the wild type strain PAO1 and the QS mutants
      respectively, and the expression of the T3SS genes in these strains was compared.
      RESULTS: The expression of exoS and exoT in pqsR mutant was increased
      significantly. The Rhl system repressed the activities of the four T3SS genes and
      the Las system had no effect. CONCLUSION: The results indicate that the Rhl and
      Pseudomonas quinolone signal (PQS) systems play an important role in regulating
      T3SS gene expression in Pseudomonas aeruginosa.

PMID- 20030053
TI  - [Characterization of Bacillus thuringiensis spoIII D gene mutation].
AB  - OBJECTIVE: Construction and characterization of a spoIII D gene deletion mutant
      of Bacillus thuringiensis. METHODS: Scanning electron microscopy and spore
      formation analysis were used to detect the ability of sporulation and formation
      of crystal protein in both the mutant and the wild strain. SDS-PAGE analysis was
      used to detect the expression of crystal protein. RESULTS: Scanning electron
      microscopy and spore formation analysis showed that spores were hardly produced
      and the crystal existed in the spoIII D deletion strain. SDS-PAGE results showed
      that the expression of cry gene in the mutant was decreased in Luria-Bertani
      medium, but not affected obviously in Schaeffer's sporulation medium (SSM).
      CONCLUSION: This indicated that the spoIII D gene was one of the essential genes
      for the sporulation of Bacillus thuringiensis, and influenced the expression of
      crystal protein.

PMID- 20030054
TI  - [Identification and functional characterization of genes induced by seed exudates
      in Azorhizobium caulinodans ORS571].
AB  - OBJECTIVE: To identify genes induced by plant seed exudates in Azorhizobium
      caulinodans ORS571. METHODS: Using promoterless kanamycin resistance gene (Km(r))
      on transposon as reporter gene and seed exudates as inducers, we screened genes
      of interest from transposon insertion mutants libraries. We streaked mutants on
      TY solid medium with Km, and another with Km and seed exudates correspondingly.
      If Km(r) is inserted into a gene that can be induced by plant signals, Km(r) will
      possibly express at the same time. Thus, mutants were selected that can grow on
      medium with Km and exudates, rather than on medium with Km. RESULTS: We
      identified a lysE family gene named asiE in strain Azc0 that can be induced by
      seed exudates and further analysis indicated that the inducing substance is
      canavanine (CAN). lacZ transcriptional fusion of asiE confirmed that its
      expression increased by ten-fold or so under the induction of CAN. Besides, lysE
      gene in four different species of Rhizobia can be induced by CAN. lysE mutants
      are all sensitive to CAN treatment whereas wild type are resistant. CONCLUSION:
      The existence of LysE can make rhizobia better survived in the rhizosphere and
      may play an important role in early stage of interaction between rhizobia and
      host plant.

PMID- 20030055
TI  - [Acid and bile tolerance and cholesterol reduction ability of Lactobacillus
      paraplantarum].
AB  - OBJECTIVE: We studied the acid and bile tolerance of Lactobacillus paraplantarum
      II 32, and examined the possible mechanisms of cholesterol reduction. METHODS:
      Strain II 32 was incubated in MRS (de Man, Rogosa, Sharpe) broth supplemented
      with cholesterol, and the cholesterol in medium was determined using gas
      chromatography. We examined cholesterol reducing ability under different
      conditions, and the relation between growth and cholesterol reduction of strain
      II 32. RESULTS: Strain II 32 showed acid resistance, bile salt tolerance and the
      cholesterol-reducing ability. The results indicated that strain II 32 survived at
      pH2 after 2 h culture and the living bacterial number could reach 10(4) cfu/mL.
      In addition, the growth of strain II 32 was delayed less than 0.5 h in MRS broth
      with 0.3% - 0.4% bile salt, when the absorbance value both increased to 0.6 unit.
      Cholesterol removed by dead and resting cells were 5.64 and 5.90 mg/g of dry
      weight compared with growing cells, which was 16.98 mg/g of dry weight.
      Cholesterol removal was greatly associated with growth of the bacteria. The
      possible mechanisms for removal of cholesterol from media were proposed:
      assimilation of cholesterol during growth, and binding of cholesterol to the cell
      surface. CONCLUSION: Strain II 32 may be promising candidates for use as a
      dietary adjunct to lower serum cholesterol in vivo.

PMID- 20030056
TI  - [Cloning and analysis of the gene encoding lycopene epsilon cyclase in Chlorella
      protothecoides CS-41].
AB  - OBJECTIVE: Lycopene epsilon cyclase (LCYE) is the key enzyme in the lutein
      synthesis pathway and catalyses linear lycopene to form cyclic epsilon-carotene,
      a presucursor of lutein. We aimed to clone the full-length cDNA of LCYE gene from
      Chlorella protothecoides CS-41, to predict the functional sites and the three
      dimensional structure of LCYE through bioinformatics analysis and to confirm its
      activities and functions. METHOD: We used RACE (rapid-amplification of cDNA ends)
      essay and RT-PCR for the cloning of the full-length cDNA of LCYE from C.
      protothecoides CS-41. The online software such as PredictProtein, Pfam HMMs and
      Swiss-Model were used in bioinformatics analysis of the amino acid sequence of
      LCYE protein. We constructed the expression vector for LCYE gene with pET-28a(+)
      and transformed into Escherichia coli BL21 (DE3). Furthermore, the E. coli strain
      containing the pAC-LYC plasmid which could accumulate lycopene was used for the
      functional confirmation of LCYE from C. protothecoides CS-41. RESULTS: A 2107 bp
      cDNA (GenBank Accession No. FJ752528) sequence was cloned with 1731 bp open
      reading frame, encoding a putative LCYE, from C. protothecoides CS-41. Homology
      studies showed that the deduced amino acid sequence of LCYE gene had a
      significant similarity with the corresponding sequences of other green algae and
      higher plants. It shared the highest sequence identity, up to 67%, with the LCYE
      gene from Chlamydomonas reinhardtii. One typical lycopene cyclase protein domain
      (Pfam05834) was predicted between the 48th-459th amino acid. In addition, the
      sequence between 261th -284th was one typical conserved lycopene cyclase protein
      motif. The SDS-PAGE result showed that the LCYE gene was overexpressed in
      Escherichia coli BL21 (DE3) after the addition of IPTG. The prokaryotically
      expressed LCYE protein was able to transfer the color of the E. coli strain
      containing the pAC-LYC plasmid from pink to yellow. CONCLUSION: The full-length
      cDNA sequence of LCYE gene was successfully cloned with the size of 2107 bp.
      Several typical motifs were found and the three-dimensional structure of LCYE was
      constructed from Bioinformatics analysis. The generated phylogenetic tree showed
      the closest relationship between C. protothecoides CS-41 and C. reinhardtii among
      the listed organisms. Finally, the expression product of the LCYE gene cloned in
      the study was confirmed to hold the function and activity of lycopene epsilon
      cyclase.

PMID- 20030057
TI  - [Effects of organic solvents and inhibitors on the decolorization activity of
      TpmD expressed in Pichia pastoris].
AB  - OBJECTIVE: We studied the effects of different organic solvents and inhibitors on
      the decolorization of recombinant triphenylmethane dyes decolorization enzyme
      (TpmD), expressed extracellularly from Pichia pastoris. METHODS: The recombinant
      TpmD was purified by ultrafiltration and Ni2+ affinity chromatography. The
      decolorization activity for malachite green was determined by UV-visible
      spectrophotometer. We studied the effects of some organic solvents and inhibitors
      on TpmD activity through the rate of decolorization decreased using malachite
      green as the substance. We also compared the difference between dithicthreitol
      (DTT) and NADH as the cofactor in assisting the decolorization by monitoring the
      dissolved oxygen consumption and the end products. RESULTS: The effect of
      methanol on the enzymatic activity was weak since TpmD still retained its high
      activity in the reaction environment containing 10% - 20% methanols. The ethanol
      and acetone made the enzymatic activity fade away quickly. Dimethylsulfoxide in
      low concentration was propitious to keep the TpmD activity, although 30%
      dimethylsulfoxide inhibited the enzymatic activity lost in a half.
      Ethylenediaminetetraacetic acid (EDTA) of low concentration, L-cysteine and NaN3
      all exhibited only weakly inhibitory effects; higher concentrated (25 mmol/L)
      EDTA could strongly inhibit enzymatic activity and sodium dodecylsulfonate (SDS)
      inhibited the activity completely. The effect of DTT on TpmD activity was beyond
      the expectation. It could substitute of coenzyme NADH to assist and accelerate
      the enzyme in decolorizing reaction. We found that the dissolved oxygen
      consumption behaviors and reaction end products measuring by UV-Visible full wave
      scan were completely different between the reactions assisted with DTT or NADH.
      This is the first report about DTT which can act as a cofactor for a
      decolorization enzyme. CONCLUSION: The effects of different organic solvents and
      inhibitors on the enzymatic activity of TpmD are very different. By the dissolved
      oxygen assay and the end products analysis, we concluded that the decolorizing
      reaction assisted with DTT was a novel reaction process. The mechanism of
      reaction with DTT as cofactor is completely different from that with NADH as
      coenzyme.

PMID- 20030058
TI  - [Population dynamics and antagonism toward Fusarium oxysporium f. sp.
      Vasinfectum. and Verticillium dahliae Kleb of endophytic bacteria from cotton].
AB  - OBJECTIVE: To explore population dynamics of endophytic bacteria and obtain
      antagonistic endophytic bacteria toward Verticillium dahliae Kleb (Vd), Fusarium
      oxysporium f. sp. Vasinfectum (Fov) from cotton. METHODS: Root, stem and leaf
      samples were surface-disinfested, and subsequently used to isolate endophytic
      bacteria by diluting plate counting method. We assayed antagonism of the isolated
      endophytic bacteria toward three pathogens: Vd (V107, which is a highly virulent
      defoliating isolate and V396, which is a mildly virulent non-defoliating
      isolate), Fov (F108) using a dual culture method, and analyzed the 16S rDNA
      sequence of doubly antagonistic endophytic bacteria (DAEB) isolates toward both
      Vd and Fov. RESULTS: The population size of endophytic bacteria in root was
      significantly larger than that in leaf and stem. The populations at seedling
      stage were generally lower than those at the flowering/maturing stage in root,
      the populations in stem and leaf were fluctuant at different development stages,
      but variation law was not observed obviously. Furthermore, although no
      significant differences of the population densities in root were found among 6
      cotton cultivars, the population densities in stem and leaf showed cultivar
      differences. The proportion of endophytic bacteria antagonizing Vd (V107, V396)
      and Fov (F108) in root was higher than that in stem/leaf, moreover, the amount of
      endophytic bacteria antagonizing toward V107 was less than that toward V396/F108.
      Based on 16S rDNA sequence analysis, all 44 DAEB isolates consisted of two phyla,
      i.e., Bacteroidetes (1 out of 44) and Proteobacteria (43 out of 44), and fell
      into 8 genera. The genus enterobacter (18 out of 44) and Pantoea (15 out of 44)
      were predominant. Notably, ten DAEB isolates demonstrated <97% sequence
      similarity with the most similar sequences of strain deposited in the Ribosomal
      Database, these DAEB isolates might be potential novel species. CONCLUSION: This
      article suggested that plant genotype, development stage, and tissue influenced
      the population of endophytic bacteria. We discovered that DAEB with predominant
      and various genus existed in cotton. Endophytic bacteria in cotton could serve as
      a pool for discovering biocontrol agent toward cotton pathogens.

PMID- 20030059
TI  - [Diversity of nirS-type denitrifying bacteria under different nitrogen fertilizer
      management in wheat soil].
AB  - OBJECTIVE: To study the effect of inorganic nitrogen fertilizer on nirS-type
      denitrifiers' community in the wheat soil. METHODS: We constructed nirS gene
      libraries of two different treatments of soil: soil fertilized with inorganic
      nitrogen fertilizer (B-UN) and without nitrogen fertilizer (B-NN). And we used
      restriction fragment length polymorphism (RFLP) method to analyze the nirS-type
      denitrifiers' diversity. RESULTS: There were 27 operational taxa units (OTUs) in
      each treatment after Msp I and Afa I digestion and only nine OTUs existed in both
      treatments. The ecological indexes such as Shannon-Wiene index, Simpon index,
      richness index and evenness index of two different soils were nearly equivalent.
      However, significant difference was found between the OTU clusters from clone
      libraries of different treatments. Eleven representative clones were sequenced.
      The similarities of ten sequences were from 73% to 95% to the sequences of the
      database. There was one sequence which had no similar nucleotide identities in
      database. CONCLUSION: The application of inorganic nitrogen fertilizer altered
      significantly the nirS-type denitrifiers' community in the wheat soil.

PMID- 20030060
TI  - [Construction and characterization of an attenuate strain apxIC-/P36+ of
      Actinobacillus pleuropneumoniae serovar 10].
AB  - OBJECTIVE: To construct an attenuate Actinobacillus pleuropneumoniae serovar 10
      strain apxIC-/P36+ for new vaccine development. METHODS: The mutant was
      constructed by transconjugation and counter-selection and then verified by PCR,
      western blot and sequence analysis. A transconjugation plasmid pEICALDH was
      constructed and transformed into donor strain Escherichia coli X7213. After
      mixing the donor cells with A. pleuropneumoniae acceptor cells, we cultivated the
      mixture for 6 hours and plated on solid medium containing chloromycetin. Then the
      Cm(R) positive clones were picked and inoculated into liquid medium without any
      antibiotic. Cultures were pelleted, plated on sucrose plates and incubated
      overnight. Finally, Sucrose-resistant colonies (SucB(R)) were selected and
      considered as mutant. RESULTS: Compared with parental strain, the mutant have the
      same growth rate in vitro and reduced virulence in mice; additionally, the animal
      experiment indicated that the mutant strain can successfully induce as good
      immune response as the parental strain, despite of deletion of apxIC gene.
      CONCLUSION: In conclusion, we successfully constructed the attenuate strain apxIC
      /P36+ of Actinobacillus pleuropneumoniae serovar 10, and this mutation system
      will facilitate development of live attenuated vaccines.

PMID- 20030061
TI  - [Biological character of porcine circovirus type 2 with site mutation at
      interferon stimulation reaction element (ISRE) like region in Rep gene promoter].
AB  - OBJECTIVE: To explore the biological function of the interferon stimulation
      reaction element (ISRE) like motif CTGAAAACGAAAGA within porcine circovirus type
      2 (PCV2) Rep promoter. METHODS: Two recombinant PCV2 strains, namely PCV2 1740(G
      C) and PCV2 1741(A-T), were constructed by transfecting PK15 cells with site
      mutated infectious clone of PCV2 strain Denta. Replication character, genetic
      stability and reactive character to porcine interferon alpha (poIFN-alpha) were
      compared among parental PCV2 and the two mutant viruses. RESULTS: The ISRE like
      motif in Rep promoter was not necessary for the replication of PCV2 because two
      site-mutated viral genome clones both produced infectious virus. In contrast to
      parental PCV2, the viral antigen positive PK15 cells of the two site-mutated PCV2
      were decreased. PCV2 1740(G-C) was genetically stable in the PK15 cell while PCV2
      1741(A-T) was found to have another two nucleotide mutated from 1744AC1745 to
      1744TT1745 between 3rd and 7th passage in the PK15 cell. After treated with 100
      U/mL porcine interferon alpha, the viral antigen positive PK15 cells and virus
      genomes of parental PCV2 and two site-mutated viruses were both increased. But
      the enhancement rate of the two site-mutated PCV2 was significantly lower than
      parental PCV2. CONCLUSION: Site-mutation of ISRE like motif in Rep promoter
      decreased the replication and poIFN-alpha induced enhancement of PCV2 in PK15
      cells. According to these above results, it maybe speculated that ISRE like motif
      in PCV2 Rep gene promoter contain a functional element and it may contribute to
      the interferon inducible enhancement of virus replication in PK15 cells.

PMID- 20030062
TI  - [Quantitative detection of NADH by in vitro bacterial luciferase bioluminescent].
AB  - OBJECTIVE: The study aimed at establishing the bacterial luciferase: FMN-NADH
      oxidoreductase bioluminescent system in vitro and evaluating its potential for
      quantitative detection of NADH. METHODS: By optimizing the amount of substrates,
      we set up the coupled luciferase: FMN-NADH oxidoreductase bioluminescent system
      in vitro, based on the crude extract from Photobacterium leiognathi YL. RESULTS:
      The in vitro coupled bacterial luciferase: FMN-NADH oxidoreductase bioluminescent
      system was: 1 mL crude extract, 27 mmol/L Dodecane 100 microL, 10 mmol/L FMN-Na
      0.5 microL and 0.14 mmol/L NADH 300 microL. Furthermore, we developed a method
      for quantitative detection of NADH according to the bioluminescence of NADH
      catalyzed of bacterial luciferase: FMN-NADH oxidoreductase system in vitro. A
      good linear relationship of NADH concentration was in a range of 1.0 x 10(-10) to
      1.0 x 10(-8) mol/L. CONCLUSION: The bacterial luciferase: FMN-NADH oxidoreductase
      system used to measure NADH concentration was a good attempt to detect living
      bacterial cells in the fields of environment, food sanitation and other related.

PMID- 20030063
TI  - [Cloning of Nisin resistent gene nisI from Lactococcus lactis and its application
      as a food grade selection marker].
AB  - OBJECTIVE: To construct an E. coli-L. lactis shuttle expression vector with nisI
      as a food grade selection marker. METHODS: According to the sequence of Nisin
      resistant gene nisI reported by GenBank, the nisI fragment was amplified by
      polymerase chain reaction with pLEB590 as template. After being sequenced, the
      amplicon was confirmed by Blast from NCBI. Then, the nisI was subcloned into the
      E. coli-L. lactis shuttle vector pMG36e, resulting in the plasmid pMG36e-NisI.
      The recombinant strain MG1363/pMG36e-NisI was obtained when the plasmid pMG36e
      NisI was transformed into L. lactis MG1363 competent cell by electroporation.
      RESULTS: When the medium contained 20 IU Nisin/mL, the recombinant strain
      carrying pMG36e-NisI showed the same growth curve and genetic stability as L.
      lactis MG1363. CONCLUSION: The nisI gene could be used as a selection marker for
      construction of a food grade expression vector.

PMID- 20030064
TI  - [Isolation and identification of seven thermophilic and anaerobic bacteria from
      hot springs in Tengchong Rehai].
AB  - OBJECTIVE: In order to study the taxonomic characteristic and physiological,
      biochemical properties of anaerobic bacteria from hot springs in Tengchong Rehai,
      Yunnan Province, China. METHODS: Using Hungate anaerobic technique We isolated
      seven strains from hot springs in Tengchong Rehai, Yunnan province, and analyzed
      their 16S rRNA gene sequences. RESULTS: The seven isolates were rod-shaped, Gram
      negative, obligate anaerobe, and spores formation was not observed. All strains
      could grow well at 70 degrees C. Growth of strain RH0802 occurred between 60 and
      80 degrees C, optimally around 70 degrees C. The pH range for its growth was
      between 5.5 and 8.5, with an optimum around 7.0. Strain RH0802 grew on a wide
      range of carbon sources, including glucose, starch, mannitol, mannose, ribose,
      maltose, cellobiose, xylose, fructose, galactose, xylan and glycerol, but it
      could not utilize sucrose or pyruvate. 16S rRNA gene phylogenetic analysis showed
      that the maximum similarity between the five strains and the strains of genus
      Caldanaerobacter was up to 98%, except RH0804 and RH0806, which reached to 96%
      and 93%, respectively. The two isolates were presumed to be potential novel
      species. The GenBank accession numbers of RH0802 to RH0808 were FJ748766,
      FJ748762, FJ748761, FJ748763, FJ748765, FJ748764 and FJ748767. CONCLUSION: The
      results showed that the seven thermophilic anaerobes belonged to the genus
      Caldanaerobacter.

PMID- 20030065
TI  - Identification of two marine fungi and evaluation of their antivirus and
      antitumor activities.
AB  - OBJECTIVE: To identify two marine fungi and evaluate the inhibitory effects of
      their crude extracts on Tobacco mosaic virus and two tumor cell lines. METHODS:
      Crude extracts was obtained by extracting with MeOH and evaporated in vacuo. The
      extracts was water-soluble fraction which was dissolved in water, and the other
      fraction was water insoluble. The fungi were identified by morphology and
      Internal Transcribed Spcer (ITS) rDNA molecular methods. The inhibitory effect on
      Tobacco mosaic virus was evaluated by indirect enzyme linked immunosorbent assay,
      and the anti-tumor activity was tested by methyl thiazolyl tetrazolium method.
      RESULTS: The fungi were identified as Penicillium oxalicum and Neosartorya
      fischeri. There crude extracts inhibited Tobacco Mosaic Virus and two tumor cell
      lines. The active fraction named 0312F1 inhibited Tobacco Mosaic Virus and tumor
      cell lines and was water-soluble. The fraction named 1008F1 inhibited Tobacco
      Mosaic Virus and was insoluble in water, whereas the fraction inhibited tumor
      cell lines was water-soluble. CONCLUSION: The active fraction named 0312F1
      inhibited Tobacco Mosaic Virus was different from that named 1008F1 inhibited
      Tobacco Mosaic Virus. The active fraction named 0312F1 inhibited tumor cell lines
      was the same as that named 1008F1. Furthermore, the inhibitory activity of water
      soluble fraction named 0312F1 against BEL-7404 cell line was much higher than
      that against SGC-7901 cell lines, whereas the inhibitory activity of active
      fraction named 1008F1 against SGC-7901 cell line was much higher.

PMID- 20030066
TI  - [Expression profile analysis of intestinal Caco-2 cells treated with
      Lactobacillus acidophilus NCFM].
AB  - OBJECTIVE: Lactobacillus acidophilus NCFM is a probiotic strain that promotes
      human health. We evaluated the influence of Lactobacillus acidophilus NCFM on the
      genetic expression patterns in the Caco-2 cells. METHODS: Caco-2 cells were
      treated with Lactobacillus acidophilus NCFM for 2h. The total RNA of cells was
      extracted. Hybridization with Human Genome U133 Plus 2.0 Array was performed. The
      image scanning and data analysis were performed subsequently. Genes with
      significant expression changes were selected and analyzed. To support the
      microarray data, three striking difference genes were studied using Real-time RT
      PCR. RESULTS: Microarrays analysis showed that the expression levels of 508 genes
      were altered as compared with the control 473 of them were up-regulated, and 35
      were down-regulated. It was supposed that many genes in Caco-2 cell were induced,
      so that Lactobacillus acidophilus NCFM could play a part in immune system
      process, antioxidant activity, biological adhesion, cholesterol absorption and so
      on. Three striking difference genes CCL2, PTX3 and TNFRSF9 which involved immune
      system process were validated by Real-time RT PCR. And the results of Real-time
      RT PCR showed the same expression trend as in microarray. CONCLUSION: Based on
      the results of gene expression alterations, the beneficial function of
      Lactobacillus acidophilus NCFM could be more greatly and deeply understood than
      ever before, and the mechanism of lactic acid bacteria would be revealed.

PMID- 20030067
TI  - [Construction and characterization of a novel baculovirus vector based on the
      White spot syndrome virus immediately-early promoter].
AB  - OBJECTIVE: To construct a universal baculovirus vector for efficient gene
      expression in both invertebrate and vertebrate cell lines. METHODS: Using the Bac
      To-Bac system, we genetically engineered the immediately-early 1 gene promoter
      (ie1 promoter) from White spot syndrome virus into a baculovirus vector that was
      pseudotyped with Vesicular stomatitis virus glycoprotein (VSV G). We placed the
      enhanced green fluorescent protein (EGFP) gene under the control of iel promoter
      in the baculovirus vector to get the reporter recombinant baculovirus, vAc-G
      EGFP. We tested the reporter EGFP gene expression in tested cell lines through
      virus infection or transduction experiments using direct fluorescence microscopy
      and Western blot analysis. RESULTS: Under the control of ie1 promoter, vAc-G-EGFP
      could efficiently express the EGFP reporter gene in both invertebrate and
      vertebrate cells. The steady-state expression level of EGFP in vertebrate cell
      lines were different from that in invertebrate Sf9 cells as reflected by Western
      blot assays. CONCLUSION: The iel promoter-based and VSV G-pseudotyped baculovirus
      vector presents a unique and effective tool to express target genes
      simultaneously in various cell systems; the novel baculovirus-mediated gene
      expression system developed in this study has the potential to be widely used in
      both basic and applied research.

PMID- 20030068
TI  - [The expression of IBDV VP2 in chicken primary myoblast cells using the
      baculovirus vector].
AB  - OBJECTIVE: To construct the recombinant baculovirus expressing Infectious bursal
      disease (IBDV) VP2 gene in the chicken primary myoblast cells. METHODS: A
      proteinase K digestion and phenol-chloroform extraction method was used to
      extract dsRNA genome from IBDV. VP2 gene was amplified by Reverse Transcription
      Polymerase Chain Reaction (RT-PCR) with the genome RNA as template. The pFastBac
      pCMV-VP2 baculovirus transfer vector was constructed by inserting VP2 gene under
      the immediate-early promoter of cytomegalovirus. The VP2 recombinant bacmid was
      obtained by Bac-to-Bac system and transfected sf9 insect cell to acquire VP2
      recombinant baculovirus. After amplification of recombinant baculovirus on cell
      passages, the recombinant virus was seeded on chicken primary myoblast cells with
      50 multiplicity of infection (MOI), and the cells were harvested at 72 hours
      after infection. RESULTS: Sodium Dodecyl Sulphate Poly-Acrylamide Gel
      Electrophoresis (SDS-PAGE) and Western blot results showed that the VP2 gene was
      successfully expressed in chicken primary myoblast cells. The product was a 48kDa
      protein and could be recognized by anti-IBDV serum. CONCLUSION: The recombinant
      baculovirus could efficiently delivery IBDV VP2 gene into chicken primary cells
      and that CMV, a mammalian-cell-active promoter, was functional in chicken primary
      cells and could direct the expression of VP2 antigen protein. The research can be
      a potential basis for the development of baculovirus vector vaccines for IBDV and
      other avian infectious disease.

PMID- 20030069
TI  - [Genetic diversity of different geographical populations of Rhodiola rosea based
      on AFLP markers].
AB  - OBJECTIVE: To research the genetic diversity of different Rhodiola rosea
      geographical populations in Tianshan Mountain, China; METHOD: The genetic
      diversity of eighteen R. rosea geological populations from six niches was
      estimated using amplified fragment length polymorphism (AFLP) markers. The data
      of amplified bands were analyzed by the software POPGENE v1.31 (32-bit) and SPSS.
      RESULT: The nine primers employed produced a total of 238 discernable and
      reproducible amplified fragments. There were 228 polymorphic bands. The
      percentage of polymorphic bands with in different populations was 95.6%. Genetic
      diversity analysis showed that average number of alleles per loci was Na =
      1.4883, effective number of alleles per loci Ne = 1.3907, Neis gene diversity
      index H = 0.2170, Shannon's information index I = 0.3108, the percentage of
      polymorphic loci P = 52.71, genetic differentiation among populations Gst =
      0.364; UPGMA cluster analysis based on genetic distance data divided eighteen
      populations into two clusters: Cluster I composed of twelve populations and
      Cluster II 6 populations which distributed in attitude upper 3 175 m; CONCLUSION:
      Our researches suggest that the best niche of R. rosea was at attitude between 3
      150-3 250 m; this region is important for the conservation of R. rosea germplasm
      resource.

PMID- 20030070
TI  - [Effects of waterlogging stress on physiological and biochemical characteristics
      of medicinal Chrysanthemum morifolium during seedling stage].
AB  - OBJECTIVE: To study the effect of waterlogging stress on medicinal Chrysanthemum
      morifolium during the seedling stage and build a reliable evaluation of flooding
      tolerance indicator system. METHOD: The three cultivars: C. morifolium cv.
      Hongxinju, C. morifolium cv. Xiaobaiju and C. morifolium cv. Changbanju were
      studied for the and the effect of waterlogging stress on their physiological and
      biochemical chracteristics. RESULT: With the extension of waterlogging, the
      content of chlorophyll and relative leaf water potential were decreased,
      meanwhile malonaldehyde (MDA), glutathione (GSH) and soluble sugar were
      increased. The catalase (CAT) of C. morifolium cv. Hongxinju rose at first and
      then dropped and CAT of C. morifolium cv. Xiaobailu and C. morifolium cv.
      Changbanju declined at first before decreased, and then dropped again. The
      peroxidase (POD) rose firstly before decrease and then increases again. After the
      waterlogging treatments which last for 4 days, the physiology and biochemistry
      characteristics can not restore to the comparison (CK) within 3 days. CONCLUSION:
      Four days waterlogging treatment had made serious damage on medicinal
      Chrysanthemum. Among three cultivars, C. morifolium Ramat. cv. Hongxinju showed
      the highest tolerance ability, while C. morifolium cv. Changbanju was the lowest,
      and C. morifolium cv. Xiaobaiu was in the middle. The malonaldehyde (MDA) and
      catalase (CAT) could be the main physiological and biochemical indexes to reflect
      the tolerance ability against waterlogging.

PMID- 20030071
TI  - [Effects of application of N, P and K and plant density on growth of Artemisia
      annua and yield of artemisinin].
AB  - OBJECTIVE: To study the effects of different doses of fertilizer N,P and K and
      different plant densities on the growth of Artemisia annua and the yield of
      artemisinin which provides a scientific basis for the A. annua cultivation and
      artemisinin production. METHOD: Field experiment with an orthogonal experimental
      design L16(45) was applied. RESULT: N, P and K in moderate supplies increased
      significantly total biomass, leaf yield, artemisinin content in leaf and
      artemisinin yield under both per plant and per plot, with N and K having more
      effective on the artemisinin content in leaves than P. Ample N benefited the
      formation of leaf yield, but excess N had a significant negative effect on
      artemisinin content. Extra supply of P or K had hardly obvious father positive
      efficiency, nor negative on artemisinin content. The plant density had strong
      negative effects on total biomass, leaf output and artemisinin yield of single
      plant (per plant), but obvious positive effects on the same indices of population
      (per plot) with the moderate densities due to the enlarging numbers of the
      population; over crowded density significantly decreased artemisinin content and
      artemisinin yield per plot. By multiple comparison, the treatment 12 (N3P4K2
      density 3) which produced the highest yields of artemisinin and artemisinin-rich
      leaf per plot was selected as the best in the experiment. CONCLUSION:
      Fertilization quantities of N, P and K fertilizer and moderate density were
      essential for A. annua growth and artemisinin production. The optimal application
      of N, P and K were respectively 300 (N), 150-300(P2O5), 210(K2O) kg x hm(-2) and
      the optimum density was 25 000 plant x hm(-2) nearby the test area in Chongqing.

PMID- 20030072
TI  - [Optimization of fermentation medium for antagonistic actinomycetes F05 of
      American ginseng rust rot pathogen].
AB  - One strain F05 which had better antagonism for American ginseng rust rot was
      obtained from continuous cropping ground, and its fermentation had been
      preliminarily studied, more over the research can further determine the optimum
      composition. The single factor and uniform design were used to optimize the
      formulation medium. The identified formulation was powder of cornstalks 3.7206%,
      (NH4)2HPO4 0.5312%, MgSO4 0.0355%, K2HPO4 0.0400%. The bacteria number was 1.57 x
      10(9) per milliliter culture solution.

PMID- 20030073
TI  - [Correlation analysis on main agronomic characters, yield per plant, artemisinin
      percentage contents and total artemisinin content per plant of Artemisia annua].
AB  - OBJECTIVE: To study the relationships among the main agronomic characters, yield
      per plant,content of artemisinin of Artemisia annua, and provide the theoretical
      basis for breeding the A. annua varieties with high-yield and high artemisinin
      content. METHOD: The main agronomic characters, yield per plant, artemisinin
      content of the wild and cultivated A. annua of Sichuan province were investigated
      and determined, and the correlated relationships among them were analyzed.
      RESULT: It was showed that the weight of dried stem per plant had very
      significantly positive correlation with the yield per plant,and the number of
      primary branches, the diameter of stem had significantly positive correlation
      with the yield per plant. The flower bud stage, first flowering stage and full
      bloom stage had significantly positive correlation with the artemisinin content.
      The first flowering stage and full-bloom stage had significantly positive
      correlation with the total artemisinin content per plant. The weight of dried
      stem per plant,the diameter of stem and the flower bud stage had significantly
      correlation with the total artemisinin content per plant. A. annua with the
      purple-stem had significant higher artemisinin content than that with the green
      stem. Through the multiple regression analysis, the classic multiple regression
      equation of the yield per plant was gained as Y = 0.06121-0.000 08X(1) +
      0.30378X(3) - 0.00051X(4) - 0.00031X5 (F = 20.15, P < 0.0001), the classic
      multiple regression equation of the artemisinin content as Y = -1.45849 -
      0.00099X(1) - 0.24079X(3) + 0.13362X(6) - 0.00719X(7) + 0.01454X(9) (F = 46.55, P
      < 0.0001), the classic multiple regression equation of the total artemisinin
      content per plant as Y = -2.67001 - 0.00249X(1) + 0.98873X(3) + 0.30037X(6) +
      0.113X(9) F = 22.62, P < 0.001). CONCLUSION: The plant with purple, thick and
      strong stem, higher plant height, moderate primary branches number and bloom
      stage, small stem-branch angle should be selected for a breeding new A. annua
      varieties with high yield and artemisinin content.

PMID- 20030074
TI  - [Isolation and identification of endophytes from Pinellia].
AB  - OBJECTIVE: To investigate the varieties of entophytes in different parts of
      Pinellia ternata. METHOD: The solidified plates were applied for the isolation of
      the endophytes, and three methods were used for the identification of endophytic
      fungi. RESULT: Eighty four strains of the entophytes were isolated from the P.
      ternata collected from 3 habitations. Endophytic fungi were morphologically
      identified belonging to 15 genera, 4 families. CONCLUSION: It indicated that the
      entophytes in P. ternata were diversity and rich, and there were some differences
      at quantity and species in different organs of P. ternata.

PMID- 20030075
TI  - [Geographical variation of Glycyrrhiza uralensis seed germination character on
      water stress].
AB  - OBJECTIVE: We studied the licorice provenance rule under the manual simulative
      water stress conditions, discussed geographical variation pattern and the ecology
      mechanism and laid the theoretical basis for the licorice seed regionalization
      and the seed allocation. METHOD: On the spot we investigated and collected seed
      materials. Setting up water potential gradient by PEG, we observed the seed
      germination characteristic through the experiment of indoor germination. RESULT:
      The sensitivity of various provenance seed germinative energy show quite
      remarkable difference for water potential reducing. Along with geographic
      longitude increasing, the seed germinates variation sensitivity increasing
      gradually to the water stress. The results of climatic factors' correlation
      analysis indicated that provenance seed germinate energy to the water stress is
      sensitive, in which the annual average temperature is low and annual
      precipitation is abundant. But it is insensitive in which the annual
      precipitation is little, the annual average temperature, average temperature in
      July and the annual average ground temperature is high. CONCLUSION: Under the
      water stress condition the licorice provenance seed germination characteristic
      exists remarkable geographical variation. Geographical variation is the result of
      natural selection.

PMID- 20030076
TI  - [Compatibility chemistry of acid-alkaline pair medicine of Dahuang and Huangbai
      in Dahuang Xiaoshi decoction].
AB  - OBJECTIVE: To determine the change pattern of alkaline and acid components of
      Dahuang and Huangbai amoung different combinations in Dahuang Xiaoshi decotion.
      METHOD: The contents of anthraquinones and berberine were determined by HPLC in
      samples of Dahuang extracts, Huangbai extracts, Dahuang and Huangbai pair
      medicine extracts, and extracts of whole recipe. RESULT: The contents of
      anthraquinones and berberine were decreased with the changes of combinations:
      from component medicinal material alone to pair medicines, and to whole recipe.
      the change pattern was more apparent in water decoctions than in ethanol
      extracts. CONCLUSION: The contents of alkaline and acid components are changed
      with different extract methods and different combinations.

PMID- 20030077
TI  - [Determination of densities of mineral drugs and their calcined products by
      sealing wax densimetry].
AB  - OBJECTIVE: To determine densities of mineral drugs and their calcined products by
      using sealing wax densimetry, and to establish the testing method of crispness
      for calcined traditional Chinese medicine. METHOD: Taking density as detection
      indicator, the accuracies of mineral drugs and their calcined products were
      investigated by sealing wax densimetry compared with direct densimetry, and the
      method of density determination was optimized. RESULT: The density values
      measured by two methods investigated above were significantly different (P <
      0.01), the density values of Pyritum, Haematitum, calcined Pyritum and calcined
      Haematitum measured by direct densimetry were increased 1.66%, 9.43%, 96.72% and
      9.02%, respectively compared with that measured by sealing wax densimetry.
      CONCLUSION: Sealing wax densimetry is suitable for the density determination of
      mineral drugs and their calcined products with its high accuracy, whereas direct
      densimetry'is not suitable for the density determination of mineral drugs and
      their calcined products.

PMID- 20030078
TI  - [Swelling property of common hydrophilic polymers and their use in push-pull
      osmotic-pump tablets].
AB  - OBJECTIVE: To investigate the feasibility of swelling hydrogel instead of
      polyethylene oxide as swelling polymer in push-layer of push-pull osmotically
      controlled-release tablets. METHOD: The swelling patterns of tablets made of pure
      polymers were studied by immerging the tablets into purified water and testing
      their size at different time points. The push-pull osmotic-pump tablets were
      prepared and their release patterns in vitro were studied and compared by their
      similar factor (f2). RESULT: Tablets with different swelling materials all showed
      satisfying release pattern in vitro and their release ratio at 12 h were all
      above 80%. CONCLUSION: With its release rate and cumulative release percentage at
      12 h, the mixture of HPMC K15M and CMCNa in ratio of 1:1 is the best choice
      instead of polyethylene oxide as swelling polymer in push-layer.

PMID- 20030079
TI  - [Preparation and in vitro evaluation of brucine-loaded polylacticacid
      nanoparticles].
AB  - OBJECTIVE: To prepare and evaluate brucine-loaded polylacticacid nanoparticles
      (Bru-PLA-NPs). METHOD: The Bru-PLA-NPs were prepared by solvent diffusion method.
      The physical, chemical properties and in vitro release behavior of the prepared
      Bru-PLA-NPs were evaluated, respectively. RESULT: The mean particle size of the
      prepared Bru-PLA-NPs was 95 nm with polydispersity index of 0.362. The zeta
      potential was -15.68 mV. The mean loading and entrapment efficiency of Bru were
      7% and 37%, respectively. Compared with Bru solution, an obvious sustained
      release behavior of Bru from Bru-PLA-NPs was observed in the in vitro release
      experiment. CONCLUSION: The Bru-PLA-NPs prepared by solvent diffusion method
      exhibit small particle size, high Bru-loading efficiency, and obvious sustained
      release in vitro

PMID- 20030080
TI  - [Dual index information markedly similar sequence clustering analysis on IR
      fingerprint spectra of extracts of Guifu Dihuang and Jingui Shenqi pills with
      ethanol].
AB  - OBJECTIVE: To establish, a novel method, Dual index information markedly similar
      sequence clustering analysis to identify and control the quality of formula
      Chinese patent medicine. METHOD: Based on common and variation peak ratio dual
      index sequence analysis proposed by authors, a new equation was built up, in
      which the common inherited and variant information could be integrated into
      unique information represent. It described the properties of biological samples
      simply and synthetically. The dual index information markedly similar sequence
      were determined and used to cluster samples. RESULT: The novel approach was
      applied for pattern recognition of IR fingerprint spectra of components of Guifu
      dihuang and Jingui shenqi pills, composed of extremely similar components
      extracted with ethanol, the two pills could be classified accurately and
      distinctly. CONCLUSION: The dual index information markedly similar sequence
      clustering method is an excellent one-fit pattern recognition one fit to analyze
      biologically complex samples.

PMID- 20030081
TI  - [Chemical constituents from roots of Distylium myricoides].
AB  - OBJECTIVE: To study the chemical constituents from the roots of Distylium
      myricoides. METHOD: The chemical constituents were isolated and separated with
      chromatographic techniques, and structures were identified by spectroscopic
      methods. RESULT: Eight phenolic compounds were isolated and identified as: 4
      hydroxy-2-methoxyphenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (1), 4-hydroxy
      3-methoxy-phenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (2), 3,4,5-tri
      methoxyphenol 1-O-beta-D-(6'-O-galloyl) glucopyranoside (3), 1,2,3,4,6-penta-O
      galloyl-beta-D-glucopyranoside (4), methyl gallate (5), ethyl gallate (6), 3,4
      dihydroxybenzoic acid (7), gallic acid (8). CONCLUSION: All compounds were
      isolated from the genus Distylium for the first time.

PMID- 20030083
TI  - [Chemical constituents from twigs of Garcinia xipshuanbannaensis].
AB  - OBJECTIVE: To study the chemical constituents of the twigs of Garcinia
      xipshuanbannaensis. METHOD: The compounds were isolated by column chromatography
      with silica gel, RP-18 and Sephadex LH-20, and their structures were elucidated
      by spectroscopic analysis. RESULT: Fifteen compounds were obtained and
      identified, which were bannaxanthone E (1), xanthochymol (2), isoxanthochymol
      (3), cycloxanthochymol (4), osajaxanthone (5), gentisein (6), mangostinone (7),
      kaempferol (8), quercetin (9), vitexin (10), 2"-O-acetylvitexin (11), 3
      acetoxyoleanolic acid (12), (-)-epicatechin (13), beta-sitosterol (14) and
      daucosterol (15), respectively. CONCLUSION: Compounds 4-9 and 11-13 were isolated
      from the plant and compounds 11-13 were obtained from the genus Garcinia for the
      first time.

PMID- 20030082
TI  - [Non-alkaloid constituents of Gelsemium elegans].
AB  - OBJECTIVE: To study the non-alkaloid chemical constituents of Gelsemium elegans.
      METHOD: Compounds were isolated and purified by repeated column chromatography,
      and their structures were elucidated by spectroscopic methods. RESULT: Ten
      compounds were isolated and their structures were identified as tamarixin (1),
      tamarixetin 3-O-beta-D-galactopyranoside (2), scopolin (3), scopoletin (4),
      uradine (5), caffeic acid (6), caffeic acid ethyl ester (7), ferulic acid ethyl
      ester (8), ethyl-alpha-D-fructofuranoside (9), and ethyl-beta-D-fructopyranoside
      (10). CONCLUSION: Compounds 1-3,5-10 are firstly isolated from this plant and
      compounds 1, 2, and 5-10 are isolated from the genus Gelsemium for the first
      time.

PMID- 20030084
TI  - [Aporphine alkaloids from branches and leaves of Polyalthia nemoralis].
AB  - OBJECTIVE: To investigate the aporphine alkaloids in the branches and leaves of
      Polyalthia nemoralis. METHOD: The compounds were isolated and purified by silica
      gel and Sephadex LH-20 column chromatographies. Their chemical structures were
      elucidated on the basis of physicochemical properties and spectral data. RESULT:
      Five aporphine alkaloids were isolated and identified as: bidebiline A (1),
      annobraine (2), lanuginosine (3), liriodenine (4), oxostephanosine (5),
      respectively. CONCLUSION: For the first time, Compounds 2 and 5 were obtained
      from Polyalthia while 1, 3 and 4 isolated from this plant. The bioassays in vitro
      against five human tumor cell lines with MTT method showed moderate cytotoxic
      activities (IC50 1 mg x L(-1)) of compounds 3-5.

PMID- 20030085
TI  - [Caffeoylquinic acid derivatives from leaves of Lonicera japonica].
AB  - OBJECTIVE: To study the caffeoylquinic acid derivatives from the leaves of
      Lonicera japonica. METHOD: The compounds were isolated by column chromatography
      and identified on the basis of physico-chemical constants and spectral analysis.
      RESULT: Five caffeoylquinic acid derivatives were isolated,and their structures
      were identified as 3,4-di-O-caffeoyl quinic acid methyl ester (1), 5-O-caffeoyl
      quinic acid methyl ester (2), 3,4-di-O-caffeoyl quinic acid (3), 1,3-di-O
      caffeoyl quinic acid (4) and chlorogenic acid (5), respectively. CONCLUSION:
      Compounds 2, 4 were obtained from this genus for the first time. Compounds 1, 3
      were obtained from this plant for the first time.

PMID- 20030086
TI  - [Rapid simultaneous determination of main nucleosides in Cordyceps sinensis with
      LC-ESI-MS].
AB  - OBJECTIVE: To establish an LC-MS method for rapid simultaneous determination of
      adenine,adenosine and cordycepin in Cordyceps sinensis. METHOD: An electrospray
      ionization (ESI) interface and selective ion monitoring (SIM) mode were used. The
      analytical column was a Shimadzu VP-ODS column (2.0 mm x 150 mm) and the mobile
      phase was water-methanol-formic acid (92:7:1). Methanol was used as extraction
      solvent and 2-chloroadenosine was used as internal standard for this assay.
      RESULT: The regression equations and coefficient were Y = 0.07264X + 0.00622 and
      r = 0.9987 for adenine, Y = 0.1597X + 0.0146 and r = 0.9991 for adenosine, Y =
      0.1942X + 0.0186 and r = 0.9994 for cordycepin. The linear range was 0.8-130.0 mg
      x L(-1), 0.5 - 124.5 mg x L(-1) and 0.5-128.5 mg x L(-1) for adenine, adenosine
      and cordycepin, respectively. The average recovery was 98.76%, 99.37% and 99.26%
      for adenine, adenosine and cordycepin, respectively. CONCLUSION: This established
      method was highly sensitive, fast and selective, which can be used for rapid
      simultaneous determination of adenine, adenosine and cordycepin in C. sinensis.
      This method also can be applied for the quality control of C. sinensis.

PMID- 20030087
TI  - [Determination of triterpenoid acids in leaves of Eriobotrya japonica collected
      at in different seasons].
AB  - OBJECTIVE: To find out the change regularity of triterpenoid acids content in
      leaves of Eriobotrya japonica. (Folium Eriobotryae) in different seasons. METHOD:
      The content of triterpenoid acids was determined by RP-HPLC. RESULT: The content
      changes of oleanolic acid, ursolic acid, corosolic acid were minor in the
      different seasons. The content of oleanolic acid and ursolic acid were highest in
      April while the content of corosolic acid was highest in July. The content of
      maslinic acid has a significant change, the material which collected in November
      has the highest content in a year. CONCLUSION: The content of triterpenoid acids
      changes regularly.

PMID- 20030088
TI  - [Chromatographic fingerprints of triterpenoid constituents of Ganoderma lucidum].
AB  - OBJECTIVE: To establish chromatographic fingerprints of triterpenoid compounds in
      ganoderma RP-HPLC for the quality control of ganoderma. METHOD: HPLC fingerprints
      were established. The chromatographic conditions were as follows: the separation
      was performed on a Diamonsil C18 column (4.6 mm x 250 mm, 5 microm), using a
      gradient elution with acetonitrile-water containing 0.8% perchloric acid as the
      mobile phases. The flow rate was 0.9 mL x min(-1), the detection wavelength was
      254 nm and the temperature of column was at ambient temperature. The common
      patterns of HPTLC and HPLC fingerprints were separately obtained through
      "Chromafinger" solution software, and quality assessments were analyzed by
      similarity. RESULT: The HPLC fingerprint pattern of G. lucidum consists of 18
      peaks, among them 6 peaks were identified by chemical reference substances.
      CONCLUSION: This study provided theory and experimental data in order to
      comprehensively evaluate the quality of ganoderma.

PMID- 20030089
TI  - [GC-MS fingerprint analyses of fatty acids in peach seed].
AB  - OBJECTIVE: To investigate the GC fingerprint of fatty acids in peach seed,and
      provide evidences for quality assessment on peach seed. METHOD: Capillary gas
      chromatography was applied in analysis of fatty acids in peach seed, and the
      distinctive information was confirmed by GC-MS with hierarchical cluster and
      species similarity analysis. RESULT: The GC fingerprint containing distinctive
      information was obtained after investigation of peach seeds from 34 varieties and
      origins. CONCLUSION: With Good reproducibility, fingerprints established for
      peach seeds provided an effective method for quality control.

PMID- 20030090
TI  - [Comparative research of different Bupleurum chinense composition to influence of
      hepatotoxicity of rats and oxidative damage mechanism].
AB  - OBJECTIVE: To compare the influence of different Bupleurun chinense composition
      to the degree of hepatotoxicity damage to rats and oxidative damage mechanism.
      METHOD: To successively lavage alcohol extracted and water extracted B. chinense
      composition to rats for 30 days, the general conditions were observed and the
      related index of liver function, the content of total-SH in serum, the content of
      MDA, the activity of SOD and the content and activity of GSH and GSH-Px in serum
      and liver tissue were detected. RESULT: Alcohol and water extracted B. chinense
      composition all could induce the increases of the activity of ALT and AST in
      serum, liver weight and the ratio of liver to body, and the content of MDA and
      induce the decreses of the content of total -SH in serum, the content of GSH, and
      the activity of SOD and GSH-Px in serum and liver tissue. The above-mentioned
      changes gradually aggravated with dose increasing, and there was significant
      difference compared with control group with distilled water. CONCLUSION: The
      different B. chinense composition all can induce hepatotoxicity damage, and the
      channel of hepatic damage is related with the peroxidative damage mechanism. The
      degree of hepatotoxicity damage caused by the alcohol extracted composition is
      more serious than that by the water extracted composition.

PMID- 20030091
TI  - [Experiment research of Jiajian Yunvjian granules on hyperthyroidism graves].
AB  - OBJECTIVE: To investigate the effects and the related mechanisms of Jiajian
      Yunujian (JJYNJ) granules, which were made from traditional Chinese medicinal
      prescription, on hyperthyroidism graves. METHOD: Except that in the normal group,
      all mice were injected 350 mcirog x kg x d(-1) L-Thyroxin sodium to establish the
      hyperthyroidism graves model. The model mice were divided randomly into model
      control group, 3 different groups of JJYNJ granules at oral dosage of 2.17, 4.33,
      8.66 g x kg(-1), every day and thiamazole group at oral dosage of 10 mg x kg(-1)
      every day, respectively. The body weight, heart/body weight index, heart rate
      (HR), spontaneous activity and oxygen consumption of all the mice were measured.
      The serum T3, T4 levels were evaluated with the method of RIA. Meanwhile, the
      effect of JJYNJ granules and thiamazole on iodine uptake by thyroid was
      determined by radio-assay. RESULT: JJYNJ granules could improve the symptoms
      caused by thyroxin, increase body weight (P < 0.05), reduce heart/body weight
      index, spontaneous activity and oxygen consumption (P < 0.05). The HR of model
      group was (794.5 +/- 47.8) beats x min(-1), significantly faster than that of
      normal group (682.5 +/- 116.4) beats x min(-1). Those of low, middle and high
      JJYNJ granule group were (736.9 +/- 66.6), (742.1 +/- 62.3), (715.8 +/- 102.8)
      beats x min(-1) respectively, obviously slower than that of model group (P <
      0.05). The serum T3, T4 levels of model group were (3.85 +/- 0.960), (234.46 +/-
      58.11) microg x L(-1), significantly higher than those of normal group (0.99 +/-
      0.30), (65.94 +/- 13.94) microg x L(-1), P < 0.01). Those of middle, high of
      JJYNJ granule group were (2.57 +/- 0.81), (164.27 +/- 72.63) microg x L(-1) and
      (2.70 +/- 0.55), (157.26 +/- 35.03) microg x L(-1). Those of thiamazole group
      were (2.88 +/- 0.59), (172.65 +/- 39.73) miicrog x L(-1). These values were
      significantly lower than those of model group. Thiamazole could significantly
      inhibit the iodine uptake in thyroid (P < 0.01), but JJYNJ granules did not block
      that obviously. CONCLUSION: JJYNJ granules could significantly improve the
      symptoms of experimental hyperthyroidism graves. Its mechanisms may be different
      from that of thiamazole, which is related to inhibiting the synthesis of thyroxin
      in thyroid.

PMID- 20030092
TI  - [Research of Herba Artemisiae Scoporiae inhibits the hepatic lipotoxicity].
AB  - OBJECTIVE: To study the efficiency and effect mechanism of Herba Artemisiae
      Scoporiae inhibits the hepatic lipotoxicity model in vitro. METHOD: Preparation
      rat regular serum and medicine serum. Under the safty of medicine thickness by
      toxicity testing, normal and model groups were added 10% normal rat serum, Herba
      Artemisiae Scoporiae group was added 10% medicine serum incubation for 24 h, FFA
      was added to all the groups but the normal incubation for 24 h. The indices were
      tested below: the content of serum tumor necrosis factor alpha (TNF-alpha) by
      ELISA, cellular triglyceride content (TG), Oil Red Staining; protein expression
      of cellular Bcl-2 Assaciated X protein (Bax), phospho-IKB (P-IkappaB) and
      Cathepsin B (ctsb) by Western Blotting; gene expression of cellular TNF-alpha,
      Bax and ctsb by real-time PCR; the expression and distribution of ctsb observed
      by immunofluorescence. RESULT: After being incubated with FFA for 24 hours, TG
      deposition of HepG2 in the model group increased markedly. Compared with normal
      group, not only the content of serum TNF-alpha, but also the protein expression
      of cellular ctsb, P-IkappaB and mRNA expression of ctsb, TNF-a increased
      significantly. Contrast to model group, TG deposition decreased markedly in the
      Herba Artemisiae Scoporiae group. The Herba Artemisiae Scoporiae inhibited TNF
      alpha content, the protein expression of cellular ctsb, P-IkappaB and mRNA
      expression of TNF-alpha significantly. CONCLUSION: Herba Artemisiae Scoporiae has
      a direct inhibition on HepG2 steatosis and TNF-alpha secretion induced by long
      chain FFA. The effect mechanism of Herba Artemisiae Scoporiae inhibits the
      hepatic lipotoxicity has close relationship with inhibition on the protein
      expression and mRNA expression of ctsb.

PMID- 20030093
TI  - [Vasorelaxational effects of total alkali Sophora alopecuroids on rabbit aorta in
      vitro].
AB  - OBJECTIVE: To study the vasodilation effects of the Total alkali Sophora
      alopecuroids L (TASa) on rabbit thoracic aortic rings in vitro and the possible
      mechanisms. METHOD: Rabbit aortic rings were isolated and precontracted with
      noradrenaline (NA) and then were divided into six groups including control group,
      TASa group, TASa + 1 x 10(-5) mol x L(-1) indomethacin (Indo), TASa + 1 x 10(-5)
      mol x L(-1) propranolol (Prop), TASa + 1 x 10(-10 mol x L(-1) N(omega)-nitro-L
      arginine (L-NNA), TASa + removal of endothelium. The vasodilation effects of TASa
      were investigated. In addition, the thoracic aortic rings were pre-treated with
      TASa (40 mg x L(-1)) and then the thoracic aortic rings were treated with
      cumulative NA (110(-8)-110(-5) mol x L(-1)), KCl (6.3-100 mmol x L(-1)) or CaCl2
      (110(-5)-110(-2) mol x L(-1)). The dose response curves of aortic rings were
      recorded. RESULT: TASa can relax isolated rabbit aorta and has an obvious
      concentration-dependent relaxation (r = 0.94, P < 0.01). The relaxant effect of
      TASa was no significant reducing by removal of endothelium and by treatment with
      L-NNA, Indo or Prop. In addition, TASa can decrease the dose response curves of
      aortic rings to NA, KCl or CaCl2. CONCLUSION: The vasodilation effects of TASa
      are related to not only inhibition of intracellular calcium release, but also
      reduction to calcium flow to the interior of the cell with blockage of calcium
      channels.

PMID- 20030094
TI  - [Comparative study between Cassia obtusifolia and processed Cassia obtusifolia on
      anti-oxidation effect and NO/ET secretion].
AB  - OBJECTIVE: To observe the different effects of water soluble extracts from Cassia
      obtusifolia and processed C. obtusifolia on anti-oxidation and vasodilatation,
      and to explore the mechanism of eye-clearing effect. METHOD: Mice were randomly
      divided into three groups: normal control group, C. obtusifolia group and
      processed C. obtusifolia group. Ten male and 10 female mice were in each group.
      mice were given extracts orally 10 g (20 mL) crude drug/kg for one month, control
      group were given same volume water. Then the eyeball tissue was harvested to
      prepare homogenate to test SOD, MDA, LDH and NO. Blood was collected from
      posterior orbital venous plexus to test ET. RESULT: Both two kinds of extracts
      could raise the activity of SOD and LDH, decrease the MDA level. Extracts from C.
      obtusifolia showed higher effects on above mentioned action. Both two kinds of
      extracts increased the ratio value of NO/ET significantly, and extracts from
      processed C. obtusifolia showed higher activity. CONCLUSION: Both C. obtusifolia
      and processed C. obtusifolia extracts show obvious anti-oxidation and
      vasodilatation effects. These results may support the eye-clearing activity of C.
      obtusifolia.

PMID- 20030095
TI  - [Effect of chlorpromazine combined with Platycodon grandiflorum on change of
      dopamine in rat striatum by microdialysis].
AB  - OBJECTIVE: To study the effects of chlorpromazine combined with Platycodon
      grandiflorum on the striatal extracellular dopamine level in rats and to research
      the interaction and the mechanism of action after combining traditional Chinese
      medicine with western medicine. METHOD: Twenty four rats were randomly assigned
      into four groups: the control group, Platycodon group, chlorpromazine group and
      chlorpromazined combined with P. grandiflorum group. The level of dopamine in CSF
      microdialysis samples was detected with high performance liquid chromatography
      with electrochemical detector after administration for 10 days. RESULT: The CSF
      level of DA (1.52 +/- 0.34) microg x L(-1) was significantly higher (P < 0.01) in
      chlorpromazine combined with P. grandiflorum group than that in the
      chlorpromazine group (1.25 +/- 0.22) microg x L(-1) (P < 0.05) and that in the
      normal control (1.06 +/- 0.24) microg x L(-1) (P < 0.01). CONCLUSION: The
      combining utilization of P. grandiflorum and chlorpromazine may increase the DA
      concentration of monoamine neurotransmitters, which results in under the
      therapeutic effect is maintained, the dosage of chlorpromazine used to
      individuals are decreased and the incidence rate of the adverse reactions of
      chlorpromazine will descend.

PMID- 20030096
TI  - [Effect of Panax notoginseng on genes expression of CYP and GST in liver tissues
      of rats].
AB  - OBJECTIVE: To examine the effects of Panax notoginseng on the expression of
      cytochrome P450 (CYP) genes and glutathione S-trans-ferase (GST) genes in liver
      tissues of male SD rats. METHOD: Rats were administered P. notoginseng 2 or 4 g x
      kg(-1) bw/d by gavage daily for 14 days. The levels of gene expression of CYP1A1,
      CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and GSTml, GST-pi were examined by
      quantitative real-time reverse-transcription polymerase chain reaction
      (quantitative real time-RT-PCR) assays. RESULT: The expression of CYP1A1, CYP1A2,
      CYP2E1, CYP3A1, GSTml and GST-pi genes was not changed by 2 or 4 g x kg(-1) P.
      notoginseng treatment, But P. notoginseng significantly inhibited mRNA
      expressions of CYP2B1 (0.48-fold, P < 0.05, and 0.61-fold, P < 0.05,
      respectively) and CYP 4A1 (0.69-fold, and 0. 51-fold, respectively). CONCLUSION:
      P. notoginseng had a special inhibitory selectivity on the expression of CYP2B1
      and CYP4A1 genes in liver tissues of rats, which indicated it may be one of the
      mechanisms of actions of P. notoginseng. P. notoginseng had no effects on the
      expressions of CYP1A1, CYP1A2, CYP2E1 and CYP3A1 genes, which suggested when P.
      notoginseng co-administrated with those drugs metabolized by the above major
      metabolizing enzymes in liver, metabolic herb-drug interactions would not be
      happened.

PMID- 20030097
TI  - [Progressive studies on toxity of Strychons nuxvomica].
AB  - Strychons nuxvomica is widely used by clinic and individual owing to its
      officinal value. Since toxic dose and therapeutic dose are very close, the
      poisoning cases are reported frequently. In this review, based on the recent
      available papers published in the PubMed and CNKI about Strychons nuxvomica, a
      traditional Chinese herbal medicine, we present the major current approaches in
      the field of composition, toxicology, pharmacokinetics, decreasing toxicity and
      increasing efficacy, in order to guide the use of S. nuxvomica in the clinic.

PMID- 20030098
TI  - [Current status, problems and countermeasures for properties theory of Chinese
      medicinal herbs].
AB  - This research has analyzed the current status, problems for the properties theory
      of Chinese medicinal herbs. Proposed that the Chinese medicine literature
      research is a foundation, the research of properties theory of Chinese medicinal
      herbs should under the'Chinese medicine theory instruction. It must use the
      modern scientific method to study and unify the Chinese medicine superiority,
      establish the standards and reveal the scientific essence of Chinese medicine
      property.

PMID- 20030099
TI  - [Review of experimental study on treatment of lung cancer with traditional
      Chinese medicine].
AB  - Lung cancer has been the leading cause of cancer death in the world. It is a
      health threat of human being. The clinical observations confirmed that there are
      some advantages by using traditional Chinese medicine (TCM) to treat lung cancer.
      TCM can improve symptoms and the quality of life, and extend lifespan of lung
      cancer patients as well. However, the specific mechanism of TCM treatment is
      unclear. Many scholars in the world have done a lot of research about the
      treatment of lung cancer with TCM. In this paper, the experimental study on
      treatment of lung cancer with TCM was reviewed over the past 10 years from the
      following aspects: inhibiting proliferation and inducing apoptosis of lung cancer
      cell, impact on the tumor cell matrix, inhibiting the angiogenesis and regulation
      the immune system. This review summarizes the research results in recent years
      and provides a reference for further study.

PMID- 20030100
TI  - [Investigation of research method of fingerprint pharmacodynamics of traditional
      Chinese medicines].
AB  - Fingerprinting techniques play a increasingly important role in the quality
      control standards of traditional Chinese medicines (TCM), research and establish
      the fingerprint about spectral-efficiency could improve the quality control of
      TCM. The necessity of the fingerprint pharmacodynamics research and the analysis
      and evaluation of the research methods in the existing literature at home and
      abroad were reviewed in this article, Combined with the author's laboratory
      research, we proposed the research methods of fingerprint pharmacodynamics of TCM
      and provided the basis for effectively promoting the the establishment and
      development of fingerprint pharmacodynamics of Chinese medicine compound
      preparations.

PMID- 20030101
TI  - [Evaluation and consideration on safety information abroad of Polygonum
      multiflorum and its preparations].
AB  - This article retrospectively analyzed the safety reports published abroad
      regarding Polygonum multiflorum and its preparations in terms of drug use and
      liver damage. The authors found that the foreign drug regulatory authorities are
      lack of in-depth analysis and investigation on the safety information of P.
      multiflorum and its preparations in the process of reporting and warning.
      Therefore, the authors consider the following factors are significant for
      scientific evaluation of traditional Chinese medicine (TCM) safety: follow-up and
      investigation of the information based on literature study, establishment of the
      safety-related information communication and feedback mechanism with foreign drug
      regulatory authorities and drafting of the guidelines for rational use of TCM.

PMID- 20030102
TI  - [Thinking and look forward to clinical study of allergic rhinitis by treatment of
      traditional Chinese medicine].
AB  - Allergic rhinitis (AR) is one kind of nose mucous membrane inflammation
      reactiveness disease, which is mediated by IgE for the environment sensitizin.
      The major clinical symptoms are: nose itch, the sneeze, nasal discharge, nasal
      obstruction and so on. It is thought that the acient disease named "Bi Qiu" has
      included AR. By comparing the AR clinical manifestation characteristic with
      trditional Chinese medicine (TCM) "Feng/wind" induced disease characteristic and
      the "Feng/wind" disease clinical manifestation characteristic, we can know that
      AR should belong to the "Feng/wind" disease category of TCM. It is shown that the
      "Feng/ wind" medicine is the most windly appeared in AR treatment formulas of TCM
      clinical research data (in each formular) in the past 10 years. To aim directly
      at three knids of problem in TCM clinical research, we discussed five problems
      which should pay close attention to the feature research, therefor to provide a
      mirror for AR clinical and experimental studies by TCM.

PMID- 20030103
TI  - [Distribution, GLUT-1 expression and early surgical intervention for infantile
      hemangioma on the face].
AB  - OBJECTIVE: To investigate the development, distribution and GLUT-1 expression of
      infantile hemangioma and to discuss the early surgical intervention for better
      results and avoiding severe complication. METHODS: The lesion site of each case
      was recorded and analyzed by SPSS V13.0 to study the distribution. The operation
      was guided by the principle of plastic surgery to remove the hemangioma. The GLUT
      1 expression was detected by immunohistochemical technique in all the resected
      samples. RESULTS: All the results were satisfactory. The GLUT-1 expression was
      positive in all the cases. The incidences in different sites were significantly
      different (P < 0.05). 71.7% of the hemangiomas were located at upper and lower
      lip, periorbital region and facial midline. It indicates that hemangioma is not
      randomly distributed. Most of them were located at the fusion of facial
      prominences during embryological development. CONCLUSIONS: Infantile facial
      hemangioma maybe originated from endothelial progenitor cells of placenta which
      migrate and implant on the fusion of facial prominences. Early surgical
      intervention is one of the best choice for infantile facial hemangioma.

PMID- 20030104
TI  - [Repair of unilateral complete cleft lip with the method of rotation descent step
      by step].
AB  - OBJECTIVE: To explore the clinical effect of the method of rotation descent step
      by step for unilateral complete cleft lip with. METHODS: The method of rotation
      descent step by step was used to repair unilateral complete cleft lip. Point X
      was located on the angular bisector of 123, rotation descent step by step and
      orbicularis oris degloved dissection were used. Nasal deformities were corrected
      at the same stage. RESULTS: From Oct. 2006 to Oct. 2008, 68 cases were treated
      with primary healing. 42 cases were followed up for less than one year. Among
      them, 3 cases showed asymmetric lip height, and 6 cases showed asymmetric lip
      width. 26 cases were followed up more than one year with only two cases of
      asymmetric lip width. CONCLUSIONS: The method of rotation descent step by step is
      very suitable for repairing unilateral complete cleft lip. The restoration of the
      malpositioned tissue is especially emphasized in this method.

PMID- 20030105
TI  - [Application of hatchet flap for buccal tissue defect].
AB  - OBJECTIVE: To evaluate the therapeutic effect of hatchet flap for buccal tissue
      defect. METHODS: The hatchet flap was designed beside the tissue defect and
      advanced to cover the defect. RESULTS: Since 2006, 13 cases were treated with
      primary healing and no flap loss. The size of the flaps ranged from 1.8 cm x 2.0
      cm to 2.5 cm x 3.5 cm. All the cases were followed up for 3 months to 1.5 years.
      The postoperative appearance was satisfactory with inconspicuous scar.
      CONCLUSIONS: Hatchet flap is very suitable for the buccal tissue defect with
      satisfactory cosmetic result. The facial natural figure is protected very well.

PMID- 20030106
TI  - [Mini-invasive midface lift with SMAS suspension and subperiosteum suspension].
AB  - OBJECTIVE: To investigate a modified midface lift for baggy deformity of low
      eyelid, zygomatic laxity, periorbital wrinkle and deep nasolabial groove.
      METHODS: Through the incision at palpebral margin for baggy eyelid, the
      dissection was performed under the periosteum of midface. The orbicularis oculi
      and zygomatic major muscles were suspended to lift the midface through the
      incision at temporal area. RESULTS: During the recent 5 years, 42 cases were
      treated with satisfactory results. CONCLUSIONS: The modified midface lift is
      easily performed with low morbidity and good safety. It is one of the best
      choices for mini-invasive midface rejuvenation.

PMID- 20030107
TI  - [Application of individualized free anterolateral thigh combined flap for tongue
      and mouth floor defects resulted from tongue carcinoma].
AB  - OBJECTIVE: To investigate the application of individualized free anterolateral
      thigh combined flap (ALTCF) for tongue and mouth floor defect resulted from
      tongue carcinoma. METHODS: From 2006 to 2008, individualized ALTCFs were used in
      31 cases of tongue and mouth floor defects resulted from tongue carcinoma. The
      nutritional perforator vessel was musculocutaneous pattern in 22 cases and
      septocutaneous pattern in 9 cases. The size of the flaps and the included muscle
      was (4-8) cm x (5-10) cm and (2-5) cm x (3-6) cm, respectively. The length of
      blood vessel pedicle was (6.81 +/- 3.23) cm. RESULTS: All the 31 free flaps
      survived with primary healing and no complication. The appearance and function
      were both satisfactory. During the follow-up period of 1-3 years, 28 cases
      survived, 2 cases were reoperated due to the neck lymphatic metastasis on the
      contralateral side. 1 case died of distant metastasis. CONCLUSIONS:
      Individualized ALTCF is a reliable flap for the tongue and month floor defects
      resulted from tongue carcinoma. Both the cosmetic and functional results are
      satisfactory with less morbidity in donor site and less complication.

PMID- 20030108
TI  - [Island sternocleidomastoid myocutaneous flap for repairing the buccal composite
      tissue defect].
AB  - OBJECTIVE: To study the application of island sternocleidomastoid myocutaneous
      flap in repairing the buccal composite tissue defect especially penetrated tissue
      defect. METHODS: The flap pedicle included upper part OF sternocleidomastoid
      muscle and occipital artery. The rotation point was located at 2 cm below the
      mastoid. The distance between the pivot point and distal border of the defect was
      the length of the muscular flap. The width of the flap was slightly larger than
      the defect, but should not be more than 7 cm. The lower border of the flap should
      not exceed 2 cm below the collar bone. The flap was elevated from the starting
      point of the sternocleidomastoid muscle and beneath it. The pedicle only
      contained muscle. The flap was transferred to the defect through the tunnel
      between the pedicle and defect. The wounds at donor sites were closed directly or
      with skin graft or local flaps. RESULTS: 12 cases were treated, including 10
      cases of buccal soft tissue tumors and 2 cases of buccal penetrated defects. All
      the musculocutaneous flaps survived with good texture, color and thickness.
      CONCLUSIONS: The island sternocleidomastoid myocutaneous flap is an ideal flap
      for large buccal composite tissue defect with reliable blood supply. It is easily
      performed and very practical.

PMID- 20030109
TI  - [Application of pedicled muscular flaps of brachioradialis in repairing wounds at
      proximal forearm resulted].
AB  - OBJECTIVE: To explore the clinical effects of pedicled muscular flaps of
      brachioradialis in repairing wounds at proximal forearm resulted from hot crush
      injury. METHODS: From February 2003 to December 2008, 5 wounds at proximal
      forearm resulted from hot crush injury were repaired with pedicled muscular flaps
      of brachioradialis. The size of muscular flaps ranged from 6 cm x 4 cm - 9 cm x 5
      cm. The wounds at donor sites were closed directly or by free skin grafts.
      RESULTS: All the muscular flaps of brachioradialis were survived completely. 4
      patients were followed up for 3 to 36 months. The cosmetic and functional results
      were satisfactory both in recipient areas and in donor sites. CONCLUSIONS:
      Pedicled muscular flap of brachioradialis can not only repair wounds at proximal
      forearm resulted from hot crush injury, but also repair extensor muscle defects.
      It is an ideal method and is very practical.

PMID- 20030110
TI  - [Treatment of complicated cavernous venous malformation with retained copper
      wires combined with pingyangmycin injection].
AB  - OBJECTIVE: To evaluate the therapeutic effect of retained copper wires combined
      with pingyangmycin (PYM) injection for complicated cavernous venous malformation.
      METHODS: The location of venous malformation was detected by physical examination
      and MRI. The copper wires in 0.2 mm width were used to puncture the lesion
      repeatedly and retained in the lesion to form a net. After that, 8 mg PYM was
      injected into the residue malformed veins. 8-10 days later, the copper wires were
      taken out and necrotic tissue was squeezed out. The wounds of punctual holes
      healed through dressing. The patients received postoperative MRI to evaluate the
      therapeutic effect. RESULTS: From Jan. 2002 to Dec. 2008, 45 cases were treated.
      The patients were followed up for 1-3 years. 51.1% (23/45) of the lesions
      shrinked markedly or even disappeared. 42.2% (19/45) of the lesions reduced.
      6.67% (3/45) of the lesions didn't change. There was no complication like
      invasive infection. CONCLUSIONS: It is very effective to treat complicated
      cavernous venous malformation with retained copper wires combined with
      pingyangmycin injection.

PMID- 20030111
TI  - [Auricular reconstruction with overlapping tissue expansion techniques].
AB  - OBJECTIVE: To investigate a method of auricular reconstruction with overlapping
      tissue expansion techniques and without skin graft. METHODS: Two tissue expanders
      were implanted subcutaneously at the mastoid. 6 patients with microtia
      (overlapping group) were treated. After completion of skin expansion, the
      expanders were removed. The autologous rib cartilage or Medpor scaffolds were
      implanted. The flap A made by the upper expanded flap was used to cover the upper
      part of the front and the back of the framework. The flap B made by lower
      expanded flap was transplanted to cover the lower part of the back of frameworks.
      The remaining expanded skin was designed to cover the postauricular wound. The
      other thirteen microtia patients who treated by the traditional auricular
      reconstruction were selected as control(traditional group). RESULTS: Skin graft
      was not necessary in the patients of overlapping groups. The appearance of the
      reconstructed ear was very satisfactory. Epidermal necrosis of 0.5 cm x 0.5 cm
      happened at the distal end of postauricular flap in one case. All the other cases
      had no complication of infection or framework exposure. The patients were
      followed up for 3-6 months. Compared with the traditional group, the scar in the
      costal donor site was inconspicuous in overlapping group (P < 0.05). The
      complication rate was lower and satisfactory rate was higher in overlapping group
      (P < 0.01 and P < 0.05). But there was hair growth in the helix of reconstructed
      ear in overlapping group. CONCLUSIONS: The overlapping expansion can provide
      enough skin for ear reconstruction. The skin graft is not necessary, resulting
      less donor site scar and low complications.

PMID- 20030112
TI  - [Distribution of deep inferior epigastric perforator vessel and application of
      the expanded perforator flaps].
AB  - OBJECTIVE: To explore the distribution of deep inferior epigastric perforator
      vessel and application of the expanded perforator flap for large scar on hand and
      forearm. METHODS: 20 healthy adults were selected to detect the distribution of
      deep inferior epigastric perforator vessel. 10 cases with cicatricial
      constriction on hand and forearm were treated with expanded perforator flap.
      RESULTS: 425 perforator points were detected on the skin surface of abdomen in 20
      adults. 80% of the points are located within the area which is 1.1 -5.8 cm far
      from the mid-line of abdomen. According to the Rand method, the percentage of the
      points in zone I , II , III were 26%, 43%, and 30%, respectively. There were few
      points in zone IV. The area around navel had a high density of points. The points
      were distributed asymmetrically at the two sides of abdomen. 10 cases were
      treated. Vascular deficiency happened at the distal end of one flap. All the
      other 9 flaps survived. CONCLUSIONS: The expanded deep inferior epigastric
      perforator flap is thin and has a large size. It is very suitable for large scar
      on forearm or hand.

PMID- 20030113
TI  - [Clinical application of medial neurocutaneous flap with perforator vessel in
      upper arm].
AB  - OBJECTIVE: To report the application of medial neurocutaneous flap with
      perforator vessel in upper arm. METHODS: Based on the perforator vessel of medial
      deep main blood vessel in upper arm and blood supply of neurocutaneous flap, as
      well as their interrelation with vascularity of fascia skin, we designed the
      medial neurocutaneous flap with perforator vessel in upper arm to repair skin
      defects in shoulder, arm and elbow joint in 5 cases. RESULTS: All the flaps
      survived completely with primary healing. The patients were followed up for 6-12
      months. The contour of flaps and the function of shoulder and elbow joint were
      satisfactory. CONCLUSION: The neurocutaneous flap has a reliable blood supply and
      easily performed. It is very desirable for repairing skin defect in upper
      extremity.

PMID- 20030114
TI  - [Correction of secondary breast deformities after removement of injected
      polyacrylamide hydrophilic gel].
AB  - OBJECTIVE: To investigate the correction of secondary breast deformities after
      removement of injected polyacrylamide hydrophilic gel (PAHG). METHODS: From March
      2003 to March 2008, 100 patients with bilateral breast augmentation with injected
      PAHG underwent operation to remove the PAHG. The age of patients ranged from 35
      to 50 years. Ultrasound and MRI were performed before operation to show the
      distribution of PAHG and the muscle infiltration around the PAHG. According to
      the PAHG distribution, muscle infiltration, skin elasticity, infection and PAHG
      residue, the patients were treated respectively with breast implants at the same
      stage or at the second stage, or without implants. RESULTS: The patients were
      followed up for 3 months to 3 years. The percentage of satisfactory, median
      satisfactory and dissatisfactory was 90%, 9%, and 1%. In the median satisfactory
      group, 3 breasts in 3 cases showed slight capsular contracture (Baker II), 8
      implants in 6 cases were palpable on the lower pole of the breasts. The middle
      aged patient in dissatisfactory group was not satisfied with the high-projected
      implants shape which were chosen by herself and placed at the second stage. Then
      implants were removed. There was no complication of implant hernia, infection,
      wound disruption, or asymmetry. CONCLUSIONS: The secondary breast deformities
      could be corrected by breast augmentation with implants. Both breast appearance
      and the psychological affection can be improved.

PMID- 20030115
TI  - [Expression of the P450arom mRNA in the glandular tissue of the pubertal mammary
      hypertrophy].
AB  - OBJECTIVE: To investigate the expression status of the P450arom mRNA in breast
      tissue of pubertal mammary hypertrophy and then explore the possible etiology of
      pubertal mammary hypertrophy. METHODS: 15 patients were selected for pubertal
      mammary hypertrophy group. Breast hypertrophy tissue specimens were collected
      from the gland excised during reduction mammaplasty. 15 patients with
      pathologically simple fibroadenoma were used as another control group. Patient
      approval of participation in this study was obtained preoperatively. The
      expression of P450arom mRNA was detected by RT-PCR in all the cases above.
      RESULTS: There was no significant difference between the pubertal mammary
      hypertrophy groups and normal groups on the expression rates of P450arom mRNA.
      But among the positive cases, the expression of P450arom mRNA within breast
      tissue were 0.202 +/- 0.048 in pubertal mammary hypertrophy group; and 0.159 +/-
      0.068 in normal group. There was significant difference between the pubertal
      mammary hypertrophy and normal groups (P < 0.05). CONCLUSION: The expression of
      P450arom mRNA in pubertal mammary hypertrophy are significantly higher than in
      normal mammary glandular tissue. The pubertal mammary hypertrophy may be related
      to the expression status of P450arom mRNA within breast tissue.

PMID- 20030116
TI  - [Expression of osteopontin and osteocalcin during distraction osteogenesis on
      rhesus with cleft palate].
AB  - OBJECTIVE: To study the mechanism of new bone formation and remodeling of
      distraction osteogenesis (DO) by analysis of the expression of osteopontin (OPN)
      and osteocalcin (OC). METHODS: Rhesus were operated to reconstruct the animal
      model of cleft palate (CP). The CP was closed by DO in experimental group(n =
      21). After consolidation of 1, 2, 4, 6, 8, 12, 24 weeks, every 3 animals were
      killed to collect the specimens, respectively. The OPN and OC and their mRNA were
      detected quantitatively by Real-time RT-PCR and ELISA, respectively. The animals
      in control group (n = 2) and sham group (n = 2) were used as control. RESULTS:
      The mRNA expression of OPN increased since 2nd week of consolidation and reached
      the peak at 4th week (7.59 +/- 0.37). The mRNA expression of OC was up-regulated
      since 4th week, and reach the peak at 6th week (7.94 +/- 0.31). Then they
      decreased to about the level in sham group at 24th week (P > 0.05). The OPN and
      OC were highly expressed during 4 to 6 weeks of consolidation. During 8 to 12
      weeks, they decreased like their mRNA expression. CONCLUSION: The
      intramembraneous new bone formation after DO can reconstruct the bone defect of
      CP. The new formed bone can be remodeled to be quite normal bone tissue.

PMID- 20030117
TI  - [Biomechanical study of internal midface distraction after different types of
      maxillary osteotomy in patients with cleft lip and palate].
AB  - OBJECTIVE: To investigate the biomechanical changes of internal midface
      distraction after different types of maxillary osteotomy in patients with cleft
      lip and palate (CLP). METHODS: 3-D finite element (FEM) analysis was used. 3-D
      models of Le Fort I, II, III osteotomy and soft tissue were established. Based on
      the new pattern of internal midface distractor, the distraction of maxillary
      complex was simulated to advance 10 mm anteriorly. The mechanical change was
      studied. RESULTS: The maxillary complex in CLP were advanced after distraction.
      Constriction of alveolar crest and palate occurred in Le Fort I osteotomy, but
      not in Le Fort II and III osteotomy. The maxillary complex was moved anteriorly
      en bloc after Le Fort III osteotomy, but some degree of rotation of maxillary
      complex was observed during the distraction after Le Fort I and II osteotomy. In
      vertical direction, the maxillary complex had more counterclockwise rotation
      after Le Fort II osteotomy. CONCLUSION: 3-D FEM analysis can be used for the
      study of internal distraction. It can reflect the maxillary movement and provide
      the theory basis for preoperative design.

PMID- 20030118
TI  - [Migration of intravenously injected adipose tissue-derived stem cells in SD rats
      with soft tissue wound].
AB  - OBJECTIVE: To explore the migration of intravenously injected adipose tissue
      derived stem cells (ADSCs) in SD rats with soft tissue wound. METHODS: 1.8 cm x
      1.8 cm full thickness skin defect and 0.5 cm in depth soft tissue defects were
      made on the back of 6 SD rats. ADSCs were isolated and cultured in vitro for 3
      passages. 2.4 x 10(6) ADSCs were labeled with DiI and transplanted into the SD
      rats through tail vein. Normal skin and wound tissue samples were collected for
      fluorescent distribution observation 24, 48 days after injection, respectively.
      RESULTS: Compared to normal skin, more fluorescent positive cells were detected
      in the margin and deep layer of the wound 24 days after operation. But it is
      accumulated within dermis and adenoid 48 days after operation. CONCLUSION: Wound
      can probably induce the migration and accumulation of intravenously transplanted
      ADSCs.

PMID- 20030119
TI  - [The effect of recombinant HSP47siRNA on the pathological scar in nude mice: in
      vivo study].
AB  - OBJECTIVE: To study the significance of HSP47 gene in the development of
      pathological scar. METHODS: The nude mice were used to reconstruct animal model
      of pathological scar. 16 days later, the mixture of recombinant HSP47siRNA and
      liposome was injected into the pathological scar in experimental group. In the
      control group, 0.25 ml PBS was injected intraperitoneally. 7 days after
      injection, the specimens were collected for detection of mRNA of HSP47, the
      collagen and for immunohistochemical study. RESULTS: In the control and
      experimental group, the collagen content was (91.71 +/- 1.24)% and (82.12 +/-
      4.79)%, respectively; the expression of HSP47mRNA was 1 042 862.01 +/- 604 194.36
      and 306 123.68 +/- 105 857.08, respectively; the expression of collagen I mRNA
      was 10 228 614.70 +/- 2 532 879.04 and 6 011 841.97 +/- 2 886 897.17,
      respectively;the scar volume was (255.60 +/- 21.34) mm3 and (132.99 +/- 24.06)
      mm3, respectively. All the above results showed significant difference between
      the two groups (P < 0.05). CONCLUSIONS: The collagen production can be reduced
      through suppression of the expression of HSP47 gene. It indicates that HSP47 gene
      enhance the development of keloid and could be used as the target of treatment.

PMID- 20030120
TI  - [Experimental study of the effect of chitosan on the capsule inside the expanded
      flap].
AB  - OBJECTIVE: To investigate the effect of chitosan on the capsule inside the
      expanded flap. METHODS: The expanders were implanted in animals with the
      treatment of chitosan(experimental group, n = 15) or without (control group, n =
      15). After taking out the expanders, the flap contraction rate was calculated.
      The samples were observed through HE, Masson dyeing and CD34 immunohistochemical
      study. The thickness of capsule inside the expanded flap was measured under
      microscope. The samples were also studied under electron microscope. RESULTS: The
      thickness of capsule was 516.000 +/- 128.491 microm in the experimental group,
      and 833.000 +/- 227.379 microm in the control group (P < 0.05). The number of
      microvessels was 8.200 +/- 2.150 per visual in experimental group, and 7.900 +/-
      1.729 per visual in control group (P > 0.05). Under the electron microscope, the
      rough endoplasmic reticulum (RER) in the capsule in experimental group decreased
      and enlarged with degranulation. The mitochondria emerged or disappeared. The
      number of ribosome was reduced. In the control group, the RER enlarged without
      degranulation, the mitochondria was intact. The number of ribosome was not
      reduced. CONCLUSIONS: The chitosan can effectively reduce the contraction of
      expanded flap through collagen secretion of fibroblast, delaying the
      differentiation from fibroblast to fiber cell, inhibiting thansform from
      fibroblast to myofibroblast. It has no effect on the microvascular generation and
      expansion, so the flap blood supply will not be affected with thicker capsule.

PMID- 20030121
TI  - [Classification, species diversity, and species distribution gradient of
      permafrost wetland plant communities in Great Xing' an Mountains valleys' of
      northeast China].
AB  - By using two-way indicator species analysis (TWINSPAN) and detrended
      correspondence analysis (DCA), this paper analyzed the environmental gradients of
      the species diversity and distribution of permafrost wetland plant communities in
      12 valleys at different latitudes of the Great Xing' an Mountains. The plant
      communities in the 12 valleys could be classified into four plant associations,
      based on the latitudes. The classification results of TWINSPAN reflected well the
      relationships between the distribution of the plant associations and the
      latitudes, and these relationships were better validated by DCA ordination. The
      species diversity increased with decreasing latitude and increasing mean annual
      temperature, mean annual precipitation, mean temperature in January, and aridity.
      The dominant and co-dominant species in shrub and herb layers were mostly
      helophytes and hygrophytes. With decreasing latitude, the helophytes and
      hygrophytes decreased or disappeared, while mesophytes increased.

PMID- 20030122
TI  - [Life form spectra, leaf character, and hierarchical-synusia structure of
      vascular plants in Thuja sutchuehensis community].
AB  - Based on the investigation of the plants in Thuja sutchuenensis community, the
      life form spectra, leaf character, and hierarchical-synusia structure in the
      community were analyzed. The life form spectra of the plants in the community
      were 73.2% of phanemphyte, 18% of hemicryptophyte, 6% of geophyte, 2% of
      chamaephyte, and 0.8% of annual plants. The leaf quality was mainly of papery and
      conaceous, which occupied 48. 8% and 36. 4% , respectively. The dominant leaf
      size was microphy (60.8%), dominant leaf margin was un-entire (56.8%), and
      dominant leaf form was simple (86%). The T. sutchuenensis community had three sub
      layers, i.e., tree layer, shrub layer, and herb layer, with lesser interlayer
      plants. Each layer was respectively composed by phanemphyte evergreen
      coniferophyte, broadleaf and deciduous broad-leaf plants, nanophanerophyte
      evergreen and deciduous broad-leaf plants, as well as hemicryptophyte, geophyte,
      and annual plants.

PMID- 20030123
TI  - [Effects of nitrogen fertilization on seasonal dynamics of soil microbial biomass
      carbon and nitrogen in Larix gmelinii and Fraxinus mandshurica plantations].
AB  - This paper studied the seasonal dynamics of soil microbial biomass C (Cmic) and N
      (Nmic), and of bacteria (cfu(b)), fungi (cfu(f)), and actinomyces (cfu(a)) in
      Larix gmelinii and Fraxinus mandshurica plantations in 2007-2008 under N
      fertilization. The two-year averaged soil Cmic and Nmic in L. gmelinii plantation
      were 13.8% and 18.3% lower than those in F. mandshurica plantation, respectively,
      but the soil Cmic and Nmic in the two plantations had similar seasonal patterns,
      being the lowest in May and the highest in September. The Cmic and Nmic, and the
      cfu(b), cfu(r), and cfu(a), were all greater in topsoil (0-10 cm) than in subsoil
      (10-20 cm), but the seasonal patterns of cfu(b), cfu(f), and cfu(a), were
      different from those of Cmic and Nmic. N fertilization decreased the Cmic and
      Nmic, and the cfu(b), cfu(f), and cfu(a), significantly, with the decrements of
      Cmic and Nmic being 24% and 63% in L. gmelinii plantation, and 51% and 68% in F.
      mandshurica, respectively, which suggested that N fertilization limited soil
      microbial biomass and altered soil microbial communities in the two plantations.

PMID- 20030124
TI  - [Soil microbial biomass in Larix gmelinii forests along a latitudinal gradient
      during spring soil thawing].
AB  - The 8-year-old Larix gmelinii forests were transplanted from four sites (Tahe,
      Songling, Sunwu, and Dailing) comprising a latitudinal gradient across the
      distribution range of L. gmelinii in Northeastern China, and the soil microbial
      biomass carbon (Cmic) and nitrogen (Nmic) in spring soil thawing period were
      measured after 3-year transplanting. Under the similar soil substrates and the
      same climate conditions, the mean values of soil Cmic and Nmic in the L. gmelinii
      forests transplanted from the four sites differed significantly, being decreased
      with increasing latitude and soil depth. The Cmic for Tahe, Songling, Sunwu, and
      Dailing averaged 554.63, 826.41, 874.81, and 1246.18 mg x kg(-1), and the Nmic
      averaged 70.63, 96.78, 79.76, and 119.66 mg x kg(-1), respectively. The Cmic and
      Nmic peaked before soil thawing, declined rapidly at the early stage of soil
      thawing, and had less change and maintained at a lower level during the period of
      soil freezing-thawing. By the end of soil thawing, the Cmic for lower latitudinal
      soils (i.e., Dailing and Sunwu) recovered faster. Soil temperature and moisture
      content during spring soil thawing affected the temporal patterns of Cmic and
      Nmic significantly, but the affecting degree depended on the stages of soil
      thawing. The Cmic and Nmic were negatively correlated to the soil temperature at
      the early stage of soil thawing, and exponentially related to the soil moisture
      content during the whole soil thawing period.

PMID- 20030125
TI  - [Soil microbial biomass and activity in relation to stand age of poplar
      shelterbelts].
AB  - Taking 5-, 10-, 15-, and 20 years old poplar (Populus euramericana cv. "N 3016")
      shelterbelts in Jianping County, Liaoning Province as test objects, the effects
      of establishing shelterbelts on the farmland soil microbial biomass carbon and
      nitrogen, and microbial activity were evaluated. After the establishment of
      shelterbelts, the concentrations of organic carbon and total nitrogen, the
      microbial biomass carbon and nitrogen, and the basal respiration in 0-15 cm soil
      layer increased after an initial decrease, being reached or exceeded the levels
      of the control after 20 years afforestation. The metabolic quotient increased
      significantly after 5 years afforestation, but decreased with increasing stand
      age. All the results suggested that under the effects of shelterbelt
      establishment, farmland soil microbial biomass and activity had obvious change.

PMID- 20030126
TI  - [Effects of salt-alkali stress on osmoregulation substance and active oxygen
      metabolism of Qingshan poplar (Populus pseudo-cathayana x P. deltoides)].
AB  - Aimed to examine the adaptability of Qingshan poplar (Populus pseudo-cathayana x
      P. deltoides) to salt-alkali stress, two-year-old cutting seedlings of the poplar
      were treated with 28 combinations of salt-alkali stress. With increasing salt
      concentration, the leaf electrolyte leakage and MDA and proline contents of test
      seedlings all showed an increasing trend, while the leaf soluble sugar content
      and SOD and POD activities increased first but decreased afterwards. The increase
      of substrate pH made the electrolyte leakage, MDA content, and POD activity
      increased and the proline and soluble sugar contents decreased after an initial
      increase, but had lesser effects on the SOD activity. When the salinity was <100
      mmol x L(-1) and the pH was increasing, all test physiological indices had a
      slight change while SOD activity kept at a higher level; when the salinity was
      >200 mmol x L(-1) and the pH was higher than 8.99, the electrolyte leakagewas
      higher than 50%, POD activity and MDA content increased obviously, proline and
      soluble sugar contents declined, and SOD activity was lower. It was concluded
      that a salt-alkali condition with salinity >200 mmol x L(-1) and pH > 8.99 was
      not appropriate to the growth of Qingshan poplar.

PMID- 20030127
TI  - [Effects of simulated acid rain on Quercus glauca seedlings photosynthesis and
      chlorophyll fluorescence].
AB  - Taking the seedlings of Quercus glauca, a dominant evergreen broadleaf tree
      species in subtropical area, as test materials, this paper studied their
      photosynthesis, chlorophyll fluorescence, and chlorophyll content under effects
      of simulated acid rain with pH 2.5, 4.0, and 5.6 (CK). After 2-year acid rain
      stress, the net photosynthetic rate of Q. glauca increased significantly with
      decreasing pH of acid rain. The acid rain with pH 2.5 and 4.0 increased the
      stomatal conductance and transpiration rate, and the effect was more significant
      under pH 2.5. The intercellular CO2 concentration decreased in the order of pH
      2.5 > pH 5.6 > pH 4.0. The maximum photosynthetic rate, light compensation point,
      light saturation point, and dark respiration rate were significantly higher under
      pH 2.5 and 4.0 than under pH 5.6, while the apparent quantum yield was not
      sensitive to acid rain stress. The maximal photochemical efficiency of PS II and
      the potential activity of PS II under pH 2.5 and 4.0 were significantly higher
      than those under pH 5.6. The relative chlorophyll content was in the order of pH
      2.5 > pH 5.6 > pH 4.0, and there was a significant difference between pH 2.5 and
      4.0. All the results suggested that the photosynthesis and chlorophyll
      fluorescence of Q. glauca increased under the effects of acid rain with pH 2.5
      and 4.0, and the acid rain with pH 2.5 had more obvious effects.

PMID- 20030128
TI  - [Physical and chemical properties of throughfall in main forest types of
      secondary forest ecosystem in montane regions of eastern Liaoning Province,
      China].
AB  - From July to September 2008, a measurement was made on the physical and chemical
      properties of bulk precipitation and throughfall in five main forest types, i.e.,
      larch plantation (LP), Fraxinus rhynchophylla stand (FR), mixed forest stand
      (MF), Korean pine plantation (KP), and Mongolian oak stand (MO), of secondary
      forest ecosystem in montane regions of eastern Liaoning Province, China.
      Comparing with bulk precipitation, the throughfall in the five forest types was
      significantly acidified (P < 0.05), and the acidification degree was in the order
      of KP > LP > MF > MO > FR. The conductivity and total dissolved solids of the
      throughfall increased significantly (P < 0.05), and were in the sequence of MO >
      FR > LP > MF > KP. The dissolved oxygen concentration of the throughfall lowered
      significantly (P < 0.05), with the rank of KP > MF > FR > MO > LP, while the Cl-
      concentration increased significantly, ranked as LP > MO > MF > FR > KP. The NO3
      concentrations of the throughfall in FR, MO and MF were higher, while those in LP
      and KP were lower than that of the bulk precipitation.

PMID- 20030129
TI  - [Responses of spatial distribution pattern of Artemisia ordosica population to
      the precipitation gradient on Ordos Plateau].
AB  - Five sites along the precipitation gradient (336-249 mm x a(-1)) from east to
      west in Ordos Plateau were selected to study the spatial distribution pattern of
      Artemisia ordosica population and its responses to the precipitation gradient by
      the methods of variance mean ratio, aggregative index, and point pattern
      analysis. The reduction of precipitation affected the spatial distribution
      pattern of A. ordosica population significantly. With decreasing precipitation
      gradient, the spatial pattern of A. ordosica population changed from uniform to
      random in small scale, and from random to clumpy in large scale, suggesting that
      in the ecological restoration of Ordos Plateau, a rational arrangement of A.
      ordosica should be made.

PMID- 20030130
TI  - [Time lag characteristics of stem sap flow of common tree species during their
      growth season in Beijing downtown].
AB  - From April to September in 2008, the stem sap flow velocity (Js) of several
      common tree species (Ginkgo biloba, Aesculus chinensis, Magnolia denudata,
      Robinia pseudoacacia, Pinus tabulaeformis and Cedrus deodara) in Beijing was
      measured by thermal dissipation method. Crosscorrelation analysis was used to
      estimate the time lag between the stem sap flow and the driving factors of canopy
      transpiration among the tree species. The Js of the six tree species was
      significantly correlated with the total radiation (Rs) and vapor pressure deficit
      (D), and the Js was lagged behind Rs but ahead of D. The maximum correlation
      coefficient of Js with Rs (0.74-0.93) was often higher than that of Js with D
      (0.57-0.79), indicating that the diurnal Js was more dependent on Rs than on D.
      The sampled tree species except P. tabulaeformis had a shorter time lag of Js
      with Rs (10-70 min) than with D (47-130 min), and there existed significant
      differences among R. pseudoacacia, P. tabulaeformis, and C. deodara. The time lag
      between the Js and the driving factors of canopy transpiration was mainly
      correlated with the tree features (DBH, tree height, canopy area, and sapwood
      area) and the nocturnal water recharge, regardless of tree species.

PMID- 20030131
TI  - [Effects of inoculating AM fungi on physiological characters and nutritional
      components of Astragalus membranaceus under different N application levels].
AB  - A pot culture with unsterilized soil as growth substrate showed that AM fungi had
      significant effects on the growth of Astragalus membranaceus (Fabaceae) under
      different N application levels. Inoculation with AM fungi promoted the AM
      infection of A. membranaceus roots, but high N application level suppressed the
      infection. Inoculating AM fungi increased the growth rate, soluble protein and
      sugar contents, and SOD, POD and CAT activities of A. membranaceus. Under 50 and
      100 mg x kg(-1) of N application, new bands of POD isozyme occurred in inoculated
      plants, and the contents of flavonoid, N, and P in A. membranaceus also had
      definite increase. The best inoculation effect was observed under the N
      application level of 50-100 mg N x kg(-1) soil.

PMID- 20030132
TI  - [Characteristics of Stipa grandis growth and reproductive biomass allocation at
      different hill position of Xilingol grassland, Inner Mongolia].
AB  - An investigation was conducted on the vegetative and reproductive biomass
      allocation of Stipa grandis at the hill-top and hill-foot of Xilingol grassland,
      and relatedness- and factor analyses were made to study the effects of hill
      position on the S. grandis seed biomass. Significant differences were observed in
      the vegetative and reproductive growth of S. grandis plants at the hill-top and
      hill-foot. At hill-foot, the height and number of non-flowering S. grandis ramets
      increased by 24.69% and 35.37%, respectively, the number of flowering ramets
      increased by 102.97%, the vegetative, reproductive, and total biomass increased
      by 44.14%, 95.59% and 47.45%, respectively, and the 100-grain mass increased by
      25.00%, as compared with those at hill-top. The seed biomass of S. grandis at
      hill-top was mainly affected by soil moisture content, while that at hill-foot
      was mainly affected by soil pH. Hill position induced the differentiation of soil
      moisture and N contents, and made the S. grandis at the fertile hill-foot
      allocating more energy to its sexual reproduction.

PMID- 20030133
TI  - [Effects of climate change on photosynthesis of Diospyros kaki under different
      soil moisture conditions].
AB  - Taking two-year-old Diospyros kaki as test material, this paper studied the
      effects of high CO2 concentration (700 micromol x mol(-1)), high temperature (5
      degrees C higher than the mean daily temperature); and their combination on the
      net photosynthesis rate (Pn), evapotranspiration (Tr), stomatal conductance (Gs),
      water use efficiency (WUE), chlorophyll content, Fv/Fm, and Fv/Fo under different
      soil moisture conditions, with the ambient air temperature and CO2 concentration
      (380 micromol x mol(-1)) as the control. Under all test soil moisture conditions,
      the combination of high CO2 concentration and high temperature decreased the Tr
      and Gs, but increased the WUE. This combination increased the Pn when the soil
      moisture content was 75%-85% and 55%-65% of field capacity, but decreased the Pn
      when the soil moisture content was 35%-45%. High CO2 concentration increased the
      Pn and WUE but decreased the Gs and Tr under all test soil moisture conditions.
      The effects of high temperature and its combination with high CO2 concentration
      on the WUE depended on soil moisture condition, with the WUE increased with
      increasing soil moisture content. Comparing with the control, high CO2
      concentration also increased the leaf Chla, Chlb, Chl (a + b), and Car
      concentrations and the Fv/Fm and Fv/Fo values, relieved the water stress, and
      increased the stress-resistance of D. kaki.

PMID- 20030134
TI  - [Effects of early growth stage shading on rice flag leaf physiological characters
      and grain growth at grain-filling stage].
AB  - In a pot experiment, rice plants were shaded during the period from transplanting
      to booting, aimed to study the effects of early growth stage shading on the rice
      growth at grain-filling stage. Comparing with the control, early growth stage
      shading decreased the tiller number by 26.72%, but increased the flag leaf area
      and soluble sugar content by 33.86% and 30.23%, respectively. The filled-grain
      number per panicle, 1000-grain mass, ultimate brown rice mass, and maximum and
      average grain-filling rates decreased by 8.65%, 4.81%, 9.74%, 20.22%, and 19.13%,
      and the effective panicle number and grain yield declined by 25.26% and 39.56%,
      respectively. The peak time of grain-filling rate (Tm) advanced 1.66 days, while
      the grain-filling time (T99) prolonged 6.80 days. For shading-tolerance variety,
      its flag leaf Chl a, Chl b, and Chl (a + b) contents at early and mid grain
      filling stages, and the protein N and soluble sugar contents and Chl a/b in its
      flag leaves at grain-filling stage all increased under early growth stage
      shading, and the ultimate brown rice mass and 1000-grain mass maintained at the
      similar levels as the control. Consequently, its grain yield reduction rate was
      lower than that of shading-sensitive variety.

PMID- 20030135
TI  - [Phosphorus use efficiency of wheat on three typical farmland soils under long
      term fertilization].
AB  - Field experiments were conducted on three typical farmland soils (loess soil,
      fluvo-aquic soil, and cinnamon fluvo-aquic soil) in Northern China to study the
      grain yield, phosphorus agronomic efficiency (PAE), and phosphorus use efficiency
      (PUE) of wheat under effects of long-term fertilizations. Seven treatments were
      installed, i.e., non-fertilization (CK), nitrogen fertilization (N), nitrogen
      potassium fertilization (NK), nitrogen-phosphorus fertilization (NP), nitrogen
      phosphorus-potassium fertilization (NPK), NPK plus straw returning (NPKS), and
      NPK plus manure application (NPKM). The averaged wheat grain yields under long
      term P fertilizations (treatments NP, NPK, NPKS, and NPKM) ranged from 2914 kg x
      hm(-2) to 6219 kg x hm(-2), being 200%-400% higher than those under no P
      fertilizations (treatments CK, N, and NK), and no significant differences were
      observed between the P fertilizations. In the early years of the experiment, the
      PAE in treatment NPK on the loess soil, fluvo-aquic soil, and cinnamon fluvo
      aquic soil was 17.0 kg x kg(-1), 20.3 kg x kg(-1), and 13.3 kg x kg(-1), and the
      PUE was 15.3%, 31.2%, and 23.8%, respectively. After 15-year fertilization, the
      PAE and PUE in treatment NPK increased annually by 3.9 kg x kg(-1) and 1.3% on
      loess soil, 2.5 kg x kg(-1) and 0.9% on fluvo-aquic soil, and 2.8 kg x kg(-1) and
      1.0% on cinnamon fluvo-aquic soil, respectively. There were no significant
      differences in the PAE and PUE among the P treatments for the same soils. In
      Northern China, long-term P fertilization could increase the wheat grain yield
      and PUE significantly, and the mean annual increase of PAE and PUE in treatment
      NPKM was higher on loess soil than on fluvo-aquic soil and cinnamon fluvo-aquic
      soil.

PMID- 20030136
TI  - [Effects of water stress on protein expression and physiological properties of
      different genotype wheat (Triticum aestivum L.) sprouts].
AB  - With drought-resistant wheat (Triticum aestivum) cultivar Changwu 134 and drought
      sensitive cultivar Zhengyin 1 as test materials, and by using -1.2 MPa PEG 6000
      to treat their seeds, this paper studied the protein expression and physiological
      properties of the sprouts under different soil moisture conditions. SDS-PAGE
      analysis showed that water stress induced the production of two new proteins with
      molecular weights of 39.5 kDa and 23.0 kDa in Changwu 134 but not in Zhengyin 1
      sprouts. Under normal water supply, the expression of the protein with molecular
      weight of 48.5 kDa in the sprouts of both Changwu 134 and Zhengyin 1 increased
      with sprout growth. This protein was preliminarily named as water-sensitive
      protein, due to its water-sensitivity and of newly discovered protein. The
      determinations of physiological properties showed that under water stress, the
      sprouts of drought-resistant Changwu 134 had higher root/shoot ratio and higher
      relative water content, but lower relative membrane permeability and lower
      malondlaldehyde content than those of drought-sensitive Zhengyin 1.

PMID- 20030137
TI  - [Low-temperature responses of enzyme activities related to fiber development of
      two cotton (Gossvpium hirsutum L.) cultivars with different temperature
      sensitivity].
AB  - Taking two cotton cultivars with difterent temperature-sensitivity during tneir
      liner strength formation as test materials, a field experiment of different
      sowing dates was conducted in Nanjing of Jiangsu Province in 2006 and 2007 to
      study the effects of low temperature on the activities and gene expression of the
      enzymes related to fiber development. The low temperature induced by late sowing
      (with the mean daily minimum temperature being 21.1, 20.5, and 18.1 degrees C
      during fiber development period) had definite effects on the enzyme activities,
      and accordingly, the fiber strength formation. Low temperature increased the
      invertase and beta-1, 3-glucanase activities, decreased the sucrose synthase and
      sucrose phosphate synthase activities, prolonged the time with higher gene
      expression level of Expansin and sucrose synthase, and delayed the expression
      peak and decreased the gene expression quantity of beta-1,3-glucanase. There
      existed significant differences in the low-temperature responses of related
      enzymes activities between the two cultivars, with the change ranges of the
      enzyme activities being larger for temperature-sensitive cultivar Sumian 15 than
      for temperature-insensitive cultivar Kemian 1, which could be the main reasons
      leading to the different temnerature-sensitivitv of the two cotton cultivars
      during their fiber strength formation.

PMID- 20030138
TI  - [Effects of no-tillage and fertilization on paddy soil CH4 and N2O emissions and
      their greenhouse effect in central China].
AB  - By using static chamber-gas chromatographic techniques, the CH4 and N2O emissions
      from the paddy soil in southeast Hubei were measured. Four treatments were
      installed, i.e., no-tillage plus no-fertilization (NT0), conventional tillage
      plus no-fertilization (CT0), no-tillage plus fertilization (NTC), and
      conventional tillage plus fertilization (CTC). In all treatments, the CH4
      emission had a seasonal variation of increasing first and decreasing then, while
      the N2O emission had no significant seasonal variation. Fertilization increased
      the CH4 and N2O emissions significantly. NT0 increased the CH4 emission and
      decreased the N2O emission significantly, compared with CT0; NTC only decreased
      the CH4 emission and increased the N2O emission slightly, compared with CTC. The
      analysis on the integrated greenhouse effect of CH4 and N2O showed that NT0
      increased the effect by 25.9%, compared with CT0, while NTC decreased the effect
      by 10.1%, compared with CTC. Therefore, a reasonable arrangement of fertilization
      and no-tillage could reduce the integrated greenhouse effect of CH4 and N2O from
      paddy field.

PMID- 20030139
TI  - [Effects of different tillage measures on upland soil respiration in Loess
      Plateau].
AB  - A field experiment was conducted in Lijiabu Town of Dingxi City, Gansu Province
      to study the soil respiration and its relations with the canopy temperature and
      soil moisture content in a rotation system with spring wheat and pea under
      effects of different tillage measures. Six treatments were installed, i.e.,
      tillage with no straw- or plastic mulch (conventional tillage, T), tillage with
      straw mulch (TS), tillage with plastic mulch (TP), no-tillage (NT), no-tillage
      with straw mulch (NTS), and no-tillage with plastic mulch (NTP). During the
      growth periods of spring wheat and pea, soil respiration had different change
      patterns, with the peaks appeared at the early jointing, grain-filling, and
      maturing stages of spring wheat, and at the 5-leaf, silking, flowering and
      poding, in spring wheat field between treatments NTS and T, and the soil
      respiration rate was significantlyand maturing stages of pea. There was an
      obvious difference in the diurnal change of soil respiration lower in NTS than in
      T; while the soil respiration in pea field had less diurnal chan ge. Soil
      respiration rate had a significant linear relationship with the canopy
      temperature of both spring wheat andpea, the correlation coefficient being the
      highest at booting stage of spring wheat and at flowering and poding stage of
      pea, followed by at grain-filling stage of spring wheat and at branching stage of
      pea. There was also a significant parabola relationship between soil respiration
      rate and soil moisture content, the correlation coefficient being higher under
      conservation tillage than under conventional tillage, with the highest under NTS.
      The moisture content in 10-30 cm soil layer of spring wheat field and that in 5
      10 cm soil layer of pea field had the greatest effects on soil respiration.
      Comparing with conventional tillage, all the five conservation tillage measures
      decreased soil respiration, with the best effects of no-tillage with straw mulch.

PMID- 20030140
TI  - [Responses of enzyme activities in different particle-size aggregates of paddy
      soil in Taihu Lake region of China to long-term fertilization].
AB  - Taking a long-term fertilized paddy soil in Taihu Lake region as research object,
      the enzyme activities in <2, 2-20, 20-200, and 200-2000 microm aggregates under
      no fertilization (NF), chemical fertilization (CF), chemical fertilization plus
      straw return (CFS), and chemical fertilization plus pig manure (CFM) were
      investigated. Fertilization promoted the formation of 200-2000 microm aggregates
      significantly. The enzyme activities differed with aggregates' particle-size.
      Urease and invertase activities were the highest in <2 microm aggregates, whereas
      the activities of cellulase, polyphenoloxidase and FDA hydrolase were the highest
      in 200-2000 microm aggregates. Fertilization, especially the combined
      fertilization of inorganic and organic fertilizers, increased the activities of
      urease, invertase, cellulase and FDA hydrolase in 200-2000 microm aggregates
      significantly. With the geometric mean (GMea) of the five test enzyme activities
      as the integrative index of soil enzyme activities, it was found that under
      fertilization, the GMea was significantly higher in 200-2000 microm aggregates,
      suggesting the high sensitivity of enzyme activities in larger particle-size
      aggregates to fertilization practices. Long-term inorganic plus organic
      fertilization could enhance the soil bio-function via the promotion of the
      formation of larger particle-size aggregates and the enzyme activities in these
      aggregates.

PMID- 20030141
TI  - [Soil enzyme activities under different restoration modes after returning
      farmland to lake in Dongting Lake area].
AB  - To reveal the effects of different restoration modes after returning farmland to
      lake on the soil biological characteristics in Dongting Lake area, the activities
      of soil saccharase, urease, phosphatase, and catalase at three typical sites
      (Xiaojicheng, Guanyuan, and Qingshanyuan) were studied. At the Xiaojicheng site
      where poplar was planted, soil catalase activity increased significantly, but the
      activities'of other three test enzymes had no significant change. At the Guanyuan
      site where reed was planted, the activities of soil saccharase and phosphatase
      had somewhat decrease, and those of urease and catalase had less change. At the
      Qingshanyuan site where natural water area was restored, the test enzyme
      activities had less changes except that the phosphatase activity decreased.
      Correlation analysis showed that the test enzyme activities had significant
      positive correlations with soil organic matter content (P < 0.01), illustrating
      that the changes in the soil organic matter content under different restoration
      modes could be the main cause inducing the changes in soil enzyme activity.

PMID- 20030142
TI  - [Effects of bio-crust on soil microbial biomass and enzyme activities in copper
      mine tailings].
AB  - Bio-crust is the initial stage of natural primary succession in copper mine
      tailings. With the Yangshanchong and Tongguanshan copper mine tailings in
      Tongling City of Anhui Province as test objects, this paper studied the soil
      microbial biomass C and N and the activities of dehydrogenase, catalase, alkaline
      phosphatase, and urease under different types of bio-crust. The bio-crusts
      improved the soil microbial biomass and enzyme activities in the upper layer of
      the tailings markedly. Algal crust had the best effect in improving soil
      microbial biomass C and N, followed by moss-algal crust, and moss crust. Soil
      microflora also varied with the type of bio-crust. No'significant difference was
      observed in the soil enzyme activities under the three types of bio-crust. Soil
      alkaline phosphatase activity was significantly positively correlated with soil
      microbial biomass and dehydrogenase and urease activities, but negatively
      correlated with soil pH. In addition, moss rhizoid could markedly enhance the
      soil microbial biomass and enzyme activities in moss crust rhizoid.

PMID- 20030143
TI  - [Characteristics of agricultural climate resources in three provinces of
      northeast China under global climate change].
AB  - Based on the 1961-2007 weather data from 72 meteorological stations in three
      provinces of Northeast China, the change characteristics of agricultural climatic
      factors including yearly and temperature-defined growing season's mean air
      temperature, > or =10 degrees C accumulated temperature, precipitation, reference
      evapotranspiration, and sunshine hours were analyzed. In 1961-2007, the yearly
      mean air temperature in the three provinces had an increasing trend, with a rate
      of 0.38 degrees C x 10 a(-1). The > or =10 degrees C accumulated temperature in
      temperature-defined growing season also had an increasing trend, and the border
      of > or =10 degrees C accumulated temperature belt moved northward and eastward.
      The area of > or =3200 degrees C x d accumulated temperature increased by 2.2 x
      10(4) km2. The belt of 2800-3200 degrees C x d moved northward about 0.85 degrees
      and eastward about 0.67 degrees, while that of 2400-2800 degrees C x d moved
      northward about 1.1 degrees. The sunshine hours decreased significantly,
      especially in the east part of Songnen Plain, central and west plains of Jilin
      Province, and west part of Liaohe River Plain. The area with sunshine hours >
      2800 h decreased from 13.6 x 10(4) km2 to 4. 1 x 10(4) km2, and the zone with
      sunshine hours 2600-2800 h moved westward about 1.5 degrees. The average sunshine
      hour in temperature-defined growing season was 1174 h. Comparing with that in
      1961-1980, the region with more sunshine hours in temperature-defined growing
      season in 1981-2007 narrowed significantly, and the zone with sunshine hours 1200
      1400 h moved westward about 0.9 degrees. In 1961-2007, both the yearly and the
      temperature-defined growing season's precipitation decreased, and the yearly
      reference evapotranspiration increased in Heilongjiang Province and in the
      eastern mountain areas of Jilin Province but decreased in the central and west
      plains of Jilin Province and in Liaoning Province. Comparing with that in 1961
      1980, the zone of reference evapotranspiration with the value of > or =900 mm in
      1981-2007 moved westward about 1 degree, and the reference evapotranspiration in
      temperature-defined growing season increased in most regions of Heilongjiang and
      Jilin Province but decreased in a rate of 0-14 mm x 10 a(-1) in most regions of
      Liaoning Province.

PMID- 20030144
TI  - [Effects of nitrogen supply level on microbial transformation of amino sugar in a
      mollisol amended with maize straw].
AB  - A 38-week laboratory incubation test at 25 degrees C was conducted to examine the
      effects of different inorganic N supply level (0, 60.3, 167.2, and 701.9 mg N x
      kg(-1) soil, noted as N0, Nlow, Nmid, and Nhig, respectively) on the microbial
      transformation of amino sugar in a mollisol amended with maize straw. Comparing
      with the control, the amendment of maize straw promoted the microbial synthesis
      of amino sugar, and at the early period of incubation, the total amount of soil
      amino sugar increased with increasing inorganic N supply, being significantly
      higher in treatments Nmid and Nhig than in treatments N0 and Nlow. With prolonged
      incubation time, the total amount of soil amino sugar decreased, and the
      decrement was higher in treatments N0 and Nlow than in treatments Nmid and Nhig.
      Different inorganic N supply level also had different effects on the dynamics of
      various amino sugars. Muramic acid exclusively originated from bacteria was more
      easily to be affected by the inorganic N supply, compared with the glucosamine
      from fungal cell wall residues. For the amendment of higher C/N maize straw, a
      sufficient N supply would be necessary for the promotion of the accumulation and
      transformation of soil amino sugar. Soil N deficiency would restrict the growth
      of soil microbes, weaken the microbial synthesis of amino sugar, and decrease the
      captured N in microbial biomass, being not beneficial to the soil N accumulation.

PMID- 20030145
TI  - [Ecological security assessment of Tangshan City based on emergy analysis].
AB  - Based on 'pressure-state-response' model and by using emergy analysis method, the
      urban ecological security assessment system and urban ecological security index
      (EUESI) were constructed, and the variation of ecological security level of
      Tangshan City in 1995-2005 was evaluated. During this period, the ecological
      security level of the city increased first and decreased then. The EUESI
      increased from 0.017 in 1995 to 0.022 in 1996, then dropped yearly, and became
      unsecure in 2003. The urban ecological security assessment method based on emergy
      analysis overcame the disadvantages of conventional assessment system, e.g.,
      numerous and repetitive indicators, non-uniform units, and poor comparability,
      and reflected the urban ecological security state more objectively, being able to
      provide scientific basis for urban ecological environment management and decision
      making.

PMID- 20030146
TI  - [Ecological safety assessment of Manas River Basin oasis, Xinjiang].
AB  - By using analytic hierarchy process and fuzzy comprehensive evaluation, an index
      system for ecological safety assessment was built, and 18 indices in the aspects
      of water resource, environment, and social economy were selected to assess the
      ecological safety of Manas River Basin oasis in 2006. In the study area, the
      ecological situation in 2006 was basically safe, with the membership degree being
      0. 3347 and the integrated evaluation score being 0. 551. The water resource
      safety index, social economy index, and environmental safety index were in the
      levels of relatively safe, extremely safe, and unsafe, respectively. Water
      resource index could represent the sustainable development degree of oasis, while
      social economy index and environment safety index could indicate the oasis
      development level and environment situation, respectively. These three indices
      could most reflect the ecological safety level of the oasis.

PMID- 20030147
TI  - [Ecosystem service valuation of Ertan Reservoir watershed in mitigating reservoir
      sand sedimentation].
AB  - By using software ArcGIS 9.2, an evaluation model was established to simulate the
      ecosystem service of Ertan Reservoir watershed in mitigating the sand
      sedimentation in the reservoir. In the meantime, sediment delivery ratio and
      universal soil loss equation were used to simulate the spatial patterns of the
      annual sediment yield and sediment retention in the watershed as well as the
      value during the service life period. In 2000, the total quantity of soil
      retention in the watershed was 12. 1 x 10(8) t x a(-1). The region with higher
      soil retention was near the main and branch streams of Yalong River, and that
      with higher sediment delivery ratio was near the streams and the Ertan Reservoir.
      The region with higher sediment yield and sediment retention was around the
      reservoir. The actual sediment yield in the study area was 629.3 x 10(4) t x a(
      1), occupying 12.7% of the actual soil erosion volume. Farmland was the most
      important source of sediment yield, with its sediment yield occupying 62.9% of
      the total. The contribution of forestland to the mitigation of reservoir sand
      sedimentation was higher than that of the other lands on a per unit area basis.
      For the reservoir's designed operating life (100 a), the total value of the
      watershed in the service of mitigating Ertan Reservoir sand sedimentation was
      2.75 billion yuan.

PMID- 20030148
TI  - [Simulation and prediction of water environmental carrying capacity in Liaoning
      Province based on system dynamics model].
AB  - By the methods of system dynamics, a water environmental carrying capacity (WECC)
      model was constructed, and the dynamic trend of the WECC in Liaoning Province was
      simulated by using this model, in combining with analytical hierarchy process
      (AHP) and the vector norm method. It was predicted that under the conditions of
      maintaining present development schemes, the WECC in this province in 2000-2050
      would be decreased year after year. Only increasing water resources supply while
      not implementing scientific and rational management of water environment could
      not improve the regional WECC, and the integration of searching for new and
      saving present water resources with controlling wastewater pollution and reducing
      sewage discharge would be the only effective way to improve the WECC and the
      coordinated development of economy, society, and environment in Liaoning.

PMID- 20030149
TI  - [Transpiration of Brassica chinensis L. in a plastic greenhouse covered with
      insect-proof nets in lower reaches of Yangtze River: a simulation study].
AB  - With the climate data inside and outside a plastic greenhouse as driving
      variables, and the greenhouse structure, insect-proof net material, and
      characteristic breadth and leaf area index of Brassica chinensis L. as
      parameters; a canopy transpiration model for greenhouse B. chinensis was
      established, based on Penmam-Monteith transpiration model. This established model
      was validated by the experimental data of independent samples in a single
      greenhouse. The results showed that in lower reaches of Yangtze River, the vent
      discharge coefficient (Cd) of greenhouse covered with 20-, 25-, and 28- mesh
      insect-proof nets was 0.771, 0.758 and 0.736, and the wind pressure coefficient
      (Cw) was 0.33, 0.37, and 0.39, respectively. The determination coefficient (R2)
      between the predicted and measured canopy transpiration rate for the sunny,
      cloudy, and overcast days in summer was 0.95, 0.91, and 0.94, root mean squared
      error (RMSE) was 0.018, 0.014, and 0.015 g x m(-2) x s(-1), and relative
      prediction error (RE) was 14.27%, 18.05%, and 15.80%, respectively, suggesting
      that this model could better predict the transpiration rate of B. chinensis in
      the plastic greenhouse covered with insect-proof nets in lower reaches of Yangtze
      River.

PMID- 20030150
TI  - [Effects of host plants on selection behavior and biological parameters of
      Bemisia tabaci Gennadius biotype B].
AB  - Based on the observation of free diffusion in petri dish and biology, the
      selection behavior and biological parameters of Bemisia tabaci Gennadius biotype
      B on host plants cucumber, eggplant, pepper, cotton, and sweet potato were
      investigated. No difference was observed in the individual number of B. tabaci on
      the five host plant leaves during the early period of free diffusion (within 2
      h), but changes were found within the following periods (4-48 h), i.e., the B.
      tabaci individuals increased on cucumber, decreased on pepper, and were
      relatively stable on eggplant, cotton, and sweet potato, which indicated that
      there were significant differences in the selectivity of B. tabaci on the five
      host plants, with the highest selectivity to cucumber and the lowest selectivity
      to pepper. Pretreatment by starvation and imidacloprid did not affect the
      selectivity of B. tabaci. There were significant differences on the honeydew
      excretion of female B. tabaci adults on the host plants, which was in the order
      of cucumber > sweet potato > cotton > eggplant > pepper. The average longevity of
      B. tabaci adults on cucumber, eggplant, sweet potato, and cotton was
      significantly longer than that on pepper, and the total number of eggs laid per
      female on cucumber, eggplant, sweet potato, and cotton (224.33, 182.33, 191.73,
      and 172.60 respectively) was significantly larger than that on pepper (only
      47.83). No significant differences were observed in the hatching rate and
      development period of the eggs on the five host plants. The development period of
      nymphs on cucumber, eggplant, sweet potato, and cotton was 10.60 d, 11.96 d,
      11.11 d, and 13.20 d, and the mortality was 5.21%, 27.78%, 17.24%, and 37.11%,
      respectively. The nymphs failed to develop normally on pepper.

PMID- 20030151
TI  - [Relationships between island characteristics and arthropod diversity in Thousand
      Island Lake].
AB  - In April, May, August, and October 2006, grid-based sampling method was adopted
      to investigate the diversity and abundance of arthropods on 50 islands in the
      Thousand-island Lake, with the effects of island area, island altitude, island
      shape, inter-island distance, and island-mainland distance on arthropod species
      richness analyzed. With the increase of island area, the richness of total
      arthropod species and that of the arthropod species with high- and low- dispersal
      ability all increased, and the relationships between island area and arthropod
      species richness corresponded to the classical island biogeography model. The
      island area, island altitude, and island shape had comprehensive effects on the
      arthropod species richness, while inter-island distance and island-mainland
      distance had less effects. The richness of total arthropod species had a
      significant positive correlation with island altitude and island shape, that of
      the arthropod species with high- dispersal ability was significantly positively
      correlated with island area and island altitude, while no significant
      relationship was observed between the richness of arthropod species with low
      dispersal ability and the island characteristics.

PMID- 20030152
TI  - [Vertical distribution and community diversity of butterflies in Yaoluoping
      National Nature Reserve, Anhui, China].
AB  - By the methods of fixed point, line intercept, and random investigation, the
      vertical distribution and community diversity of butterflies in Yaoluoping
      National Nature Reserve were investigated from 2005 to 2008. A total of 3681
      specimen were collected, belonging to 111 species, 69 genera, and 10 families,
      among which, Nymphalidae had the higher species number, individual's number, and
      diversity index than the other families. The butterflies in the study area were a
      mixture of Oriental and Palaearetic species, with the Oriental species diminished
      gradually and the Palaearetic components increased gradually with increasing
      altitude. Among the three vertical zones ( <800 m, 800-1200 m, and >1200 m in
      elevation), that of 800-1200 m had the most abundant species of butterflies; and
      among the six habitat types (deciduous broad-leaved forest, evergreen conifer
      forest, conifer-broad leaf mixed forest, bush and secondary forest, farmland, and
      residential area), bush and secondary forest had the higher species number,
      individual's number, and diversity index of butterflies, while farmland had the
      lowest diversity index. The similarity coefficient of butterfly species between
      the habitats was mainly dependent on vegetation type, i.e., the more the
      difference of vegetation type, the lesser the species similarity coefficient
      between the habitats, which was the highest (0.61) between conifer-broad leaf
      mixed forest and bush and secondary forest, and the lowest (0. 20) between
      evergreen conifer forest and bush and secondary forest.

PMID- 20030153
TI  - [Distribution patterns of giant panda in Guanyinshan and Foping nature reserves].
AB  - By using line transect method, the distribution patterns of giant panda
      population and its sympatric companion wildlife species in Foping and Guanyinshan
      nature reserves were investigated in October 2007 and April 2008, and the
      environmental factors affecting the spatial distribution of giant panda activity
      were analyzed. The giant panda population and its sympatric companion wildlife
      species in the two reserves had the similar distribution patterns, and the
      density and distribution range of giant panda were smaller in Guanyinshan than in
      Foping. Giant panda had two high-density distribution areas in Foping, but no
      activity trace in most parts of Guanyinshan. The activity trace of Budorcas
      taxicolor, Naemorhedus goral and Sus scrofa was more in Guanyinshan than in
      Foping. Anthropogenic interference might affect the distribution pattern of giant
      panda.

PMID- 20030154
TI  - [Inhibitory effects of dry Acorus calamus extracts on the growth of two water
      bloom-forming algal species].
AB  - A trial with different concentrations of aqueous extracts from dry Acorus calamus
      plants was conducted to study the effects of the extracts on Microcystis
      aeruginosa and Chlorella pyrenoidosa growth. Allelopathic effects were observed.
      High concentration ( >40 ml x L(-1)) extracts inhibited the growth of the two
      algal species at low inoculation cell density significantly (P < 0.01), with the
      maximal inhibition rate being 98.66% for M. aeruginosa and 92.38% for C.
      pyrenoidosa, while low concentration ( < 30 ml x L(-1)) extracts promoted the
      growth of C. pyrenoidosa. Neither high nor low concentration extracts had
      significant effects on the growth of the two algal species at high inoculation
      cell density (P > 0.05). The comparison of adding the aqueous extracts once and
      semiconsecutively showed that the allelochemicals in the extracts were easy to be
      degraded, suggesting that the continuous secretion of allelochemicals in natural
      water bodies could play an important role in inhibiting algal growth.

PMID- 20030155
TI  - [Physiological responses of Myriophyllum spicatum to ammonium nitrogen].
AB  - With the sediment applied with 0, 0.24%, and 0.48% NH4Cl (treatments CK, SN1, and
      SN2) as the substrate, a greenhouse experiment was conducted to study the
      physiological responses of Myriophyllum spicatum to ammonium nitrogen. The NH4+ 
      N concentration in the sediment, pore-water, and overlying-water ranged in 12.35
      870.32 mg x kg(-1), 1.09-1036.05 mg x L(-1) and 0.10-24.30 mg x L(-1),
      respectively. Comparing with those in CK, the plant height, root length, and
      fresh biomass of M. spicatum in treatments SN1 and SN2 decreased by 15.66% and
      55.52%, 45.72% and 67.65%, and 19.69% and 81.16%, respectively. The SOD activity
      in M. spicatum leaves and roots was SN1 < SN2 < CK, but the peroxidase (POD) and
      catalase (CAT) activities in the leaves were SN2 < SN1 < CK, while those in the
      roots were significant higher in SN, and SN2 than in CK. The malondialdehyde
      (MDA) contents of leaves and roots in SN1 and SN2 were increased by 46.30% and
      82.75%, and 19.66% and 55.19%, respectively. It was suggested that NH4+ -N had
      toxic effects on M. spicatum, and the higher the NH4+ -N concentration in
      sediment, the more obvious the physiological responses of M. spicatum exhibited.

PMID- 20030156
TI  - [Low water temperature tolerance and responding mode of scleractinian corals in
      Sanya Bay].
AB  - In an experimental temperature-regulated mesocosm, the low water temperature
      tolerance of five dominant scleractinian coral species Pavona decussate, Acropora
      pulchra, Acropora florida, Acropora valida, and Porites lutea in Sanya Bay was
      investigated, and their responding modes to the cold water stress were analyzed.
      The tolerance of test corals to low water temperature was closely related to
      their morphologies, with the branching corals being the most vulnerable to
      bleaching and death by separating the symbiotic polyps from their skeletons. The
      lethal low water temperature for branching Acropora corals was 14 degrees C
      lasting for 3 days, and that for foliose P. decussate was 12 degrees C lasting
      for 10 days. Massive P. lutea corals responded to low water temperature by
      forming mucus membrane, which helped to prevent the further losing of symbiotic
      algae. The corals showing strong tolerance to high water temperature also had
      strong tolerance to low water temperature, and had similar responding modes to
      both high and low water temperature, i.e., the corals didn't extend their
      tentacle first, followed by the continuous release of mucus and the discharge of
      symbiotic zooxanthellae, and finally, bleached and died.

PMID- 20030157
TI  - [Ecotoxicolgical effects of albendazole on Eisenia fetida].
AB  - By using artificial soil test, the effects of different concentration albendozole
      on Eisenia foetida's growth, survival, reproduction, and activities of superoxide
      dismutase (SOD), glutathione-sulfurtransferase (GST-S) and acetylcholine esterase
      (AchE) were studied. Low concentration (5 mg x kg(-1)) albendazole inhibited the
      reproduction of E. foetida significantly (P < 0.05), and 7 mg x kg(-1) of
      albendazole had significant effects on the growth and survival of E. foetida.
      When the albendazole concentration reached to 10 mg x kg(-1), the mortality of E.
      foetida was as high as 53%. There was a significant dose-response relationship
      between the exposure concentration of albendazole and the inhibition rate of E.
      foetida's growth and reproduction. After 21 days' albendazole exposure, the SOD
      and GST-S activities were affected significantly, but no significant dose
      response relationship was observed. Albendazole exposure had less effects on AchE
      activity. In sum, albendazole had direct toxicity on soil animals, with a
      potential ecological risk.

PMID- 20030158
TI  - [Research advances in species diversity of arbuscular mycorrhizal fungi].
AB  - Arbuscular mycorrhizal (AM) fungi are one of the important components of
      biodiversity in ecosystems. They are rich in species diversity, genetic
      diversity, and function diversity. Their taxonomy position moved forward to
      phylum, and there are 214 species belonging to 19 genera, 13 families, 4 orders,
      and 1 class reported in the world. AM fungi play a vital role in keeping
      ecological balance and enhancing ecosystem sustainable productivity. This paper
      reviewed the research advances in the species diversity of AM fungi distributed
      globally, the key factors affecting this species diversity in various ecosystems,
      and related regulation pathways. It was considered that molecular biological
      techniques would be the main approaches in the future study of AM fungal species
      diversity.

PMID- 20030160
TI  - Kant on mental disorder. Part 1: an overview.
AB  - This paper sets out Kant's anthropological account of mental disorder. I begin
      with a discussion of the nature of Kant's 'pragmatic anthropology' and the
      implications of the fact that his discussion of mental disorder takes place in
      that context. I then set out Kant's taxonomy of the mind and discuss the various
      disorders affecting the cognitive faculty and the faculties of feeling and
      desire. I end with a brief discussion of Kant's views on the causes, preventions,
      and treatments of mental disorder.

PMID- 20030159
TI  - [Cyclic imine toxin gymnodimine: a review].
AB  - Gymnodimine (GYM), an algal toxin first detected from New Zealand oysters in
      1994, is identified as a cyclic imine toxin and produced by Karenia selliformis,
      with imino nitrogen attached on loop-coil. Imine is the poisonous functional
      group of the toxin. GYM has a low oral toxicity, but its acute lethal toxicity of
      intra-peritoneal injection for mice is very high. Up to now, few reports have
      been published on the detailed information about the toxicity mechanism of GYM.
      Based on limited literatures, this paper reviewed the GYM's structure, producer,
      toxicity mechanism, carrying animals, geological distribution, degradation
      metabolism, dose-effect relation, and risk evaluation, and proposed the further
      research directions on algal toxin.

PMID- 20030161
TI  - Kant on mental disorder. Part 2: philosophical implications of Kant's account.
AB  - This paper considers various philosophical problems arising from Kant's account
      of mental disorder. Starting with the reasons why Kant considered his theory of
      mental disorder important, I then turn to the implications of this theory of
      Kant's metaphysics, epistemology and ethics. Given Kant's account of insanity as
      'a totally different standpoint... from which one sees all objects differently'
      (7: 216), the Critique of Pure Reason should be read as offering a more social
      epistemology than typically recognized. Also, mental disorders that seem to
      undermine human freedom and rationality raise problems for Kant's moral
      philosophy that his pragmatic anthropology helps to mitigate. Finally, I propose
      some implications of Kant's account of mental disorder for contemporary work on
      mental illness.

PMID- 20030162
TI  - The vocabulary of madness from Homer to Hippocrates. Part 1: the verbal group of
      mualphaiotanuomicronmualphaiota.
AB  - In Part 1 of this two-part paper, I examine the evolution of the concept of
      madness expressed by the various forms--verbal and nominal, simple and compound-
      of the verbal group of mualphaiotanuomicronmualphaiota in the archaic and
      classical periods. I point out how the divine madness is contrasted to
      pathological madness considered as a psychic and mental disease and foreseeable
      by doctors as well as curable by medications. This new procedure highlights
      rational knowledge of the Greeks about the cause and the medical care of madness.

PMID- 20030163
TI  - Foucault and the 'Anti-Oedipus movement': psychoanalysis as disciplinary power.
AB  - What psychiatry was for the anti-psychiatry movement, psychoanalysis was for the
      French 'Anti-Oedipus movement' represented by Robert Castel, Gilles Deleuze and
      Felix Guattari. Until now, the contribution of Foucault to this critical movement
      has been little known. In this paper I reconstruct in a systematic and exhaustive
      way Foucault's critique of psychoanalysis and, in particular, of the Oedipus
      complex theory. I demonstrate that this critique presupposes a very specific
      epistemology and social theory. On an epistemological level, Foucault focuses on
      the power effects of psychoanalysis as a discourse of subjectivity. On a social
      theoretical level, Foucault assumes a functionalist conception of society. These
      two aspects of Foucault's critique of psychoanalysis have not been adequately
      recognized in the discussion about his relationship to psychoanalysis (Derrida,
      Miller, Whitebook, among others). I argue that a fruitful dialogue between a
      Foucault-inspired critical social theory and psychoanalysis can take place only
      if these two distinct aspects are taken into account.

PMID- 20030164
TI  - Some aspects of a medical anthropology: pathic existence and causality in Viktor
      von Weizsacker.
AB  - 'Life is not only an "event" that happens--but also something that is suffered';
      this is the core principle of what Viktor von Weizsacker (1886-1957), the German
      physician and founder of a 'Medical Anthropology', called the 'pathic' dimension.
      The personal voice of the human being himself becomes a constitutive principle
      within the medium of science. Concepts of cause and effect are no longer
      applicable in the customary functional sense of aetiology. Even the intellect or
      spirit (Geist) can no longer be regarded as unscathed. In order to handle pathic
      'causality' Weizsacker introduced his 'pathic pentagram'. The interplay of five
      modalities--must / may / want / should / can--creates a ground or reason of
      psychological and/or somatic explanation. Necessity and freedom of a person
      appear interwoven in a constitutive manner.

PMID- 20030165
TI  - The historical roots of Theory of Mind: the work of James Mark Baldwin.
AB  - The historical development of the concepts underpinning what is currently called
      'Theory of Mind' (ToM) has received little attention. This paper deals with the
      contribution of James Mark Baldwin (1861-1934) whose work on such concepts was
      original and profound. Embedding his version of ToM into a coherent developmental
      theory of human cognition, and suggesting novel methods of observation, Baldwin
      also proposed new conceptual tools and protoconcepts such as the 'ejective-self'.
      Baldwin also wrote on the distinction between the mental and the non-mental, and
      on play and imitation. His influence on Jean Piaget, another important figure in
      the development of ToM, is briefly touched upon here, as are possible
      explanations for Baldwin's woeful absence from the 20th-century ToM hagiography.

PMID- 20030166
TI  - [Body mass index and cardiovascular events: the "obesity paradox"].
AB  - Excessive body mass among healthy subjects carries an increased risk of
      subsequent cardiovascular events. Excess weight implies the presence of white,
      viscero-abdominal fat, that promotes insulin-resistance, is infiltrated by
      macrophages, and is less differentiated compared to subcutaneous or brown fat.
      Conversely, among patients with cardiovascular disease, slim patients have a
      greater risk of recurrent atherothrombotic events than fatter patients ("obesity
      paradox"). Lean patients with cardiovascular disease, on average, have more
      comorbidities and haemorrhagic complications than their heavier counteparts, and
      probably they conceal predisposing factors that are still unknown and therefore
      difficult to treat.

PMID- 20030168
TI  - [Cheyne-Stokes respiration and heart failure: pathophysiological and clinical
      implications].
AB  - The search for the presence of Cheyne-Stokes respiration should be introduced
      into the routine diagnostic process in heart failure patients, owing to its
      clinical and prognostic implications. The analysis of this specific alteration of
      the respiratory pattern could contribute both to the understanding of its
      pathophysiological role, and to the discovery of specific treatments for heart
      failure patients, characterized by poor prognosis, despite optimal conventional
      treatment.

PMID- 20030167
TI  - [Immunosuppressant treatment in refractory myositis. Our experience].
AB  - We report our experience of treating polymyositis (PM) and dermatomyositis (DM)
      with prednisone and immunosuppressants (methotrexate [MTX], cyclophosphamide
      [CTX], cyclosporine A [CsA], mycophenolate mofetil [MMF] and intravenous
      immunoglobulins [IVIg]). We revised our series of 63 subjects with primary PM or
      DM and overlap myositis, diagnosed according to the Bohan and Peter criteria. We
      used a standardised protocol to evaluate patients, and assess treatment response.
      Complete remission was achieved in 26, 60, 82, and 85% of subjects treated with
      MTX, CTX, CsA-IVIg and MMF-IVIg, respectively. Patients receiving CsA or MMF plus
      IVIg had a significantly higher probability of maintaining complete remission at
      long-term follow-up than those treated with immunosuppressant alone. In our
      experience, IVIg as add-on treatment with CsA or MMF is useful in patients with
      myositis, even those with refractory or relapsed disease. We did not find any
      increase in the number or type of side effects.

PMID- 20030169
TI  - [Environmental factors and autoimmunity].
AB  - Autoimmune diseases have a multifactorial pathogenesis. If many genetic factors,
      such as the role of major hystocompatibility complex, are called in cause for the
      risk of these diseases, many environmental factors are discovered as actors in
      the pathogenesis. In this paper we evaluated the role of the exposition to UVB
      rays, the role of activation of vitamin-D and the development of autoimmunity. We
      also observed the role of toxic esogen agents in the air, with particular
      attention for exposition workers. Finally, the role of cigarette smoking, and the
      development of particular autoantibodies such as rheumatoid factors and anti
      cyclic citrullinated peptide in the pathogenesis of rheumatoid arthritis, are
      discussed.

PMID- 20030170
TI  - [Problems related to postoperative clinical relapse and endoscopic recurrence in
      Crohn's disease].
AB  - Crohn's disease is a chronic inflammatory condition that may involve any segment
      of the gastrointestinal tract. Up to 70% of patients with Crohn's disease will
      undergo intestinal resection during the course of their disease for
      complications, but also for the control of symptoms when medical therapy is not
      useful. At 1 year after a first resection, up to 70% of patients show an
      endoscopic recurrence and 20-30% have clinical relapse. Ileocolonoscopy is
      considered the gold standard for postoperative recurrence assessment. Several
      other risk factors for postoperative recurrence have been identified such as
      smoking, the disease activity before surgery, the ileocolonic disease, the
      younger age, the fistulising disease. Several different therapeutic approaches
      have been evaluated in the prevention of postoperative recurrence. In clinical
      practice, mesalazine is the first-line treatment used in the postoperative
      setting, despite considerable controversy as to its efficacy. Immunosuppressive
      treatment is based on scant evidence but is currently used as a second-line
      treatment in post-surgical patients at high risk for recurrence, with severe
      symptoms or with early endoscopic lesions in the neoterminal ileum. Biologic
      therapy (infliximab) is a candidate new therapy but further controlled trials are
      needed.

PMID- 20030171
TI  - [Comparison between two methods for the measurement reticulated platelet and
      their clinical significance--flow cytometry (FCM) method and IPF method Using
      automated hematology analyzer (XE-2000)].
AB  - Reticulated platelet (RP) is thought to be a useful marker for differential
      diagnosis and analysis of platelet kinetics in patients with thrombocytopenia. In
      this study, we compared two methods for the measurement of RP: flow cytometric
      (FCM) method and immature platelet fraction (IPF) method using automated
      hematology analyzer (XE-2000). There was a relatively good correlation between
      RP% measured by FCM method and IPF% measured by IPF method in patients with
      idiopathic thrombocytopenic purpura (ITP) (Y = 0.806X-0.050, r = 0.634, p <
      0.001). We then measured RP% and IPF% in 61 patients with ITP and 27 patients
      with aplastic anemia (AA). For the differential diagnosis for ITP, the
      sensitivity (82%) and specificity (93%) of FCM method were better than those of
      IPF method (sensitivity 67% and specificity 63%). Our data demonstrate the
      significant difference between two methods by analyzing clinical samples in
      parallel.

PMID- 20030172
TI  - [Fully automated immunoassay system utilizing microchip electrophoresis].
AB  - Application of microTAS (micro Total Analysis Systems) technologies utilizing
      chips with microfluidic channels to clinical diagnostic testing has drawn a lot
      of attention since it is expected to contribute to shortening reaction time,
      reduction of reagent/sample consumption, reducing instrument size, and other
      advantages of microchip electrophoresis. We have developed a fully automated
      immunoassay system by employing isotachophoresis followed by capillary gel
      electrophoresis for immunoreaction and B/F separation in microfluidic channels on
      polymer microchips. Laser-Induced Fluorescence (LIF) was used for detection of
      the sandwich immunocomplex composed of DNA-conjugate antibody, antigen and
      fluorescent dye-conjugated antibody. An immunoassay for PIVKA II was demonstrated
      on this new microTAS system utilizing the DNA-conjugated anti PIVKA II antibody
      and the fluorescent-dye labeled anti-prothrombin antibody. The resulting assay
      showed good assay performance with high sensitivity (LOD = 5mAU/mL), good
      reproducibility(CV = 1.0 - 5.7%) and good correlation with the commercially
      available PIVKA II assay kit (regression curve of y = 1.04x + 11.1, r = 0.991).
      The assay turn around time (TAT) was about 9 min. The PIVKA II assay will be
      useful for the diagnosis and prognosis of hepatocellular carcinoma.

PMID- 20030173
TI  - [Relevance of urinary protein/creatinine ratio and urinary abnormal casts].
AB  - OBJECTIVES: The quantification of 24 hrs urinary protein excretion is valuable
      for diagnosing and monitoring renal disease. However, because of its practical
      difficulties, the spot urinary protein/creatinine (P/C) ratio has been utilized.
      We aimed to evaluate the analytical performance of P/C ratio by comparing with
      the qualitative urinary protein values and the microscopic urine sediment
      analysis. METHODS: We obtained 5,538 urinary samples from the outpatients of
      Juntendo University Hospital. Testing for urinary P/C ratio was performed by
      Atlas Pro12 (cut-off 150 mg/g x Cr), urinary protein (proteinuria) was detected
      quantitatively by full-automated system ATLAS XL (cut-off 30 mg/dL). Microscopic
      exams were conducted following to the JCCLS reference method. RESULTS: The P/C
      ratio demonstrated higher sensitivity but lower specificity for urinary abnormal
      casts detected by microscopic exams compared to proteinuria (sensitivity; P/C
      87%, proteinuria 77%. specificity; P/C 74%, proteinuria 93%). From the
      comparative study with microscopic exams, both P/C and proteinuria performed high
      positive rate (> 80%) for the granular cast type and mixture cast type. For the
      cellular cast type, however, the positive rate of P/C was 56% and that of
      proteinuria was only 36%. The overall abnormal casts by microscopic exams showed
      better correlation with the positive P/C ratio than proteinuria. CONCLUSION: This
      study emphasizes that a spot urine P/C ratio is useful in screening for the
      further microscopic exams. P/C ratio can be a convincing index of urinary protein
      excretion when attenuation urine is doubted.

PMID- 20030174
TI  - [Clinical significance of apolipoprotein B-48 (apoB-48) in patients with thyroid
      disease].
AB  - Apolipoprotein B-48 (apoB-48) is a constituent of chylomicrons and chylomicron
      remnants, and its serum concentration is thought to be one of the risk factors
      for atherosclerosis. Clinically overt hypothyroidism (OH) has been associated
      with accelerated and premature coronary atherosclerosis. In the current study, we
      measured the serum apoB-48 concentration in patients with hyperthyroidism and
      hypothyroidism. We also evaluated the correlations between serum apoB-48 and
      thyroid hormones, from which a clinical significance of apoB-48 measurement in
      thyroid disease was deduced. Serum apoB-48 concentration was measured by
      chemiluminescence enzyme immunoassay (CLEIA) and it correlated with thyroid
      stimulating hormone (TSH), total cholesterol (TC), low density lipoprotein
      cholesterol (LDL-C) and triglycerides(TG), but negatively correlated with free
      thyroxine (FT4) and free triiodothyronine (FT3). In a cross-sectional study,
      serum apoB-48 concentrations were significantly higher in OH subjects (8.4 +/-
      5.4 microg/ml) compared to those in 70 hyperthyroid subjects (5.0 +/- 3.9
      microg/ml) and 50 normal subjects (6.3 +/- 4.9 microg/ml). After L-T4
      replacement, serum apoB-48 concentrations were decreased in OH patients. However,
      these changes were smaller compared to those of TSH, FT4 and FT3. Serum apoB-48
      levels and thyroid hormones and lipid profiles were measured in 31 SH patients
      and 34 normal subjects. Significant difference was noted in serum apoB-48, TG and
      TSH between patients with SH and normal. In conclusion, serum apoB-48
      concentration depends on thyroid status like TC, LDL-C and TG. Thyroid hormone
      replacement therapy may reduce serum apoB-48 concentrations in patients with OH.
      Therefore, increased serum apoB-48 concentrations may contribute to the increased
      risk of atherosclerosis and premature coronary artery disease in the hypothyroid
      state.

PMID- 20030175
TI  - [Clinical laboratory examination of diabetic patients in conjunction with
      metabolic syndrome].
AB  - Diabetic patients tend to show a reduced QOL because of macrovascular
      complications such as cerebral and myocardial infarction, as well as marked
      microvascular complications. It is important for the prevention and amelioration
      of these complications to diagnose diabetes mellitus (DM) early and effectively
      control glycemia, the blood pressure, lipids, and body weight. We examine fasting
      plasma glucose (FPG) and HbA1c for a diagnosis of diabetes at any time, but
      examine 75gOGTT for impaired glucose tolerance or DM. Examination to be necessary
      for a pathologic classification of DM is islet-associated antibody, namely, GAD
      antibody, IA-2 antibody and the measurement of IRI, blood/urinary C-peptide to
      evaluate insulin secretory ability. HOMA-R is an index of insulin resistance, and
      HOMA-beta is an index of insulin secretory ability which can be calculated from
      FPG and IRI, but we need to be aware that the insulin secretory ability of the
      patient may have decreased already. HbA1c is a standard index of glycemic
      control, but glycoalbumin measurement is suitable for disease states such as
      anemia and liver cirrhosis, and 1,5-anhydroglucitol is suitable for detecting
      changes in levels of urinary glucose. Examinations necessary for the evaluation
      of diabetic nephropathy are microalbumin and 24hr Ccr in the urine, but eGFR has
      been recently recommended instead of 24hr Ccr. We measure small dense LDL-C, RLP
      C, and Lp (a) as well as conduct conventional lipid analyses for dislipidemia
      combined with DM for qualitative as well as quantitative data. Metabolic syndrome
      is caused by the life habits of overeating and lack of exercise, leading to
      atherosclerotic disease, because insulin resistance advances from visceral fat
      accumulation. TNF-alpha and leptin levels as insulin resistance advances and
      adiponectin levels as insulin resistance improves are measured as adipocytokines
      secreted by visceral fat tissue.

PMID- 20030176
TI  - [Use of a medical checkup-data to prevent lifestyle-related disease].
AB  - In Japan, medical check-ups are available under various laws. Medical check-up
      are available for students in school (School Health Law), for workers(Industrial
      Safety and Health Law), and for residents over 40 years old (Health and Medical
      Service Law for the Aged/Elderly). From 1985, citizens' health promotion has been
      presented twice under the act on building citizen's health. Furthermore, "The act
      of health promotion for citizens in the twenty-first century (Healthy Japan 21)"
      was initiated as third health promotion act for citizens starting in 2000. The
      objectives of this act are decreasing the rate of death in late middle age,
      extending life, and realizing an improvement in the quality of life. The
      underlying concept of "Healthy Japan 21" is an emphasis on prevention and the
      Health Promotion Act was established for this concept. Since then, the policy of
      health promotion has emphasized prevention and there is a need to change the
      concepts of medical check-ups to correspond with the emphasis on prevention.
      Since 2000, the number of overweight people has increased. Therefore, this
      emphasis may not be succeeding. Fat, the great risk factor for Diabetes, is due
      to life style choices, for example, dietary habits and lack of exercise.
      Therefore, individual will is important. It was thought that one of the reason
      for the increase in the number of overweigh people is insufficient investigation
      during medical check-up and lack of guidance regarding lifestyle-related
      diseases. In 2006, the medical system reform-related law mainly concerning aged
      people was established. The prevention of lifestyle-related diseases is one of
      the important approaches in this law, and a specialized medical check-up has been
      initiated starting in April, 2008.

PMID- 20030177
TI  - [The third function (regulation of physiological function) of food for prevention
      of lifestyle-related diseases--close linkage to clinical examination].
AB  - It is well known that lifestyle-related diseases are closely related with not
      only environmental factors but also genetic factors. In addition, chronic
      lifestyle-related diseases, namely malignant neoplasm, cardiovascular diseases
      and cerebro-vascular diseases are the top three among the leading causes of
      death, and account for approximately 60% of mortality in Japan. Moreover, it is
      seriously concerned that dysregulation of adipokine secretion induced by visceral
      fat accumulation causes the clustering of various lifestyle-related diseases,
      followed by a marked increase in group with a high risk of contracting metabolic
      syndrome. Accordingly, it is an important issue to promote effective clinical
      examinations and health guidance with a focus on the prevention of metabolic
      syndrome including lifestyle-related diseases. In this review, I refer to 1)
      overview of lifestyle-related diseases such as hypertension, lipid metabolism
      disorders and diabetes, and metabolic syndrome in the national health and
      nutrition survey in Japan 2007, 2) useful clinical items for prevention of
      metabolic syndrome and those significances, 3) food for special dietary uses
      (FOSDU) and food with health claims (FHC) including food for specified health
      uses (FOSHU) and food with nutrient function claims (FNFC), 4) daily food or its
      functional component which may exert effective action such as hypolipidemic
      effect, and 5) prospects of clinical examination and study of food function. In
      conclusion, for prevention of lifestyle-related diseases, close relationship and
      mutual cooperation between clinical examination and food function study will be
      much more necessary in the future, which will contribute to the promotion of
      special health checkups and healthcare guidance focused on the prevention of
      metabolic syndrome.

PMID- 20030178
TI  - [History of the histological staining survey in the Tokyo Metropolitan Hospital].
AB  - The Tokyo metropolitan hospital society of chief medical technologist has carried
      out a staining survey once a year since 1992. This staining survey is performed
      to plan improvements of the staining technology at each hospital and reduction of
      differences among hospitals. This report describes the examination results for
      PAS stain, Papanicolaou stain, and PAM stain.

PMID- 20030179
TI  - [Protein biomarker measurement and simple/rapid diagnostics with supersensitive
      and multiplex assay, MUSTag technology].
AB  - Recently, we face the rapid progression of an aging population, and so the
      importance of preventive medicine is growing. We would all like to pursue a
      healthy life during old age through effective treatment on the basis of the early
      detection of diseases. In this situation, we have developed MUSTag (Multiple
      Simultaneous Tag) assay technology through an innovative modification of the
      immuno-PCR method for the super-sensitive and multiplex detection of target
      biomarkers. In MUSTag technology, each different oligo-tag simultaneously detects
      multiplex protein targets with extremely high-level sensitivity (more than 10
      fg(10(-15) g)/ml) in a dose-dependent manner by qRT-PCR (maximum: 3 plexes).
      Herein we report our recent results of multiple cytokine assays or disease
      specific biomarker assays using MUSTag technology, and, further, clinical results
      from patients with cancer, ischemic brain, or heart attack, who need a prompt and
      predictive diagnosis for adequate treatment.

PMID- 20030180
TI  - [IgG4-related sclerosing disease].
AB  - Autoimmune pancreatitis (AIP) is a peculiar type of pancreatitis of presumed
      autoimmune etiology. AIP is diagnosed currently based on characteristic
      radiological findings (irregular narrowing of the main pancreatic duct and
      enlargement of the pancreas) in combination with serological findings (elevation
      of serum IgG, and IgG4, and presence of autoantibodies), clinical findings
      (elderly male preponderance, occasional extrapancreatic lesions, and favorable
      response to steroid therapy), and histopathological findings (dense infiltration
      of IgG4-positive plasma cells and T lymphocytes with fibrosis and obliterative
      phlebitis in the pancreas). Based on histological and immunohistochemical
      examination of various organs of AIP patients, a novel clinicopathological entity
      of "IgG4-related sclerosing disease" has been proposed. This is a systemic
      disease that is characterized by extensive IgG4-positive plasma cell and T
      lymphocyte infiltration of various organs. Clinical manifestations are apparent
      in organs such as the pancreas, bile duct, gallbladder, salivary or lacrimal
      gland, and retroperitoneum, where tissue fibrosis with obliterative phlebitis is
      pathologically induced. AIP is not simply a form of pancreatitis but rather a
      pancreatic lesion reflecting an IgG4-related sclerosing disease. This disease
      includes autoimmune pancreatitis, IgG4-related sclerosing cholangitis, IgG4
      related cholecystitis, IgG4-related sialadenitis, IgG4-related retroperitoneal
      fibrosis. In some cases, only 1 or 2 organs are clinically involved, while in
      others 3 or 4 organs are affected. Serum IgG4 levels and immunostaining with anti
      IgG4 antibody are useful in establishing the diagnosis. Since malignant tumors
      are frequently suspected on initial presentation, IgG4-related sclerosing disease
      should be considered in the differential diagnosis to avoid unnecessary surgery.

PMID- 20030181
TI  - [The effects of a novel local ventilation system to reduce the health hazard to
      students during gross anatomy courses].
AB  - Formaldehyde or formalin is indispensable not only as a preservative but also as
      a disinfectant of cadavers for gross anatomy. It has recently attracted a great
      deal of attention as a health hazard for students and lecturers. To reduce the
      concentration of formaldehyde gas (FAG), we improved a novel local ventilation
      system of the push-pull type. This is the first report dealing with the effects
      of this ventilation system on the health of students before (over 1 ppm) and
      after (0.1 ppm) the installation. The percentages of students with lacrymal
      symptoms or airway irritation were reduced to a third of what they were before
      the installation. In particular, the number of those with continuously strong
      symptoms was reduced to a sixth of the pre-installation levels. This local
      ventilation system draws in fresh air from outside, and directs it to the
      breathing zone of the students, effectively reducing their symptoms.

PMID- 20030182
TI  - [Wnt signaling and cancer].

PMID- 20030183
TI  - [Analysis of astrocyte-derived stress-related genes].

PMID- 20030184
TI  - [To elucidate the mechanisms of pain and visceral pain].

PMID- 20030185
TI  - [Comparative cytology and histology of primary urine-producing organs].

PMID- 20030186
TI  - [Reconstruction of life history of ancient human skeletal remains based on new
      methods].

PMID- 20030187
TI  - [Morphological study of the diacylglycerol kinase family].

PMID- 20030188
TI  - [Eating disorders and central nervous system damage].
AB  - Eating and swallowing disorders are developed in various periods of feeding.
      Aspiration, one eating disorder, induces aspiration pneumonitis. Elderly people
      have higher rate of mortality from aspiration pneumonitis. It is important that
      aspiration is relate to the breathing mechanism. Both swallowing and breathing
      are regulated by a solitary tract and aspects of the central nerve system. Eating
      and swallowing disorders develop as an aftereffect of central nerve system damage
      (e.g., minimal cerebral vascular disease or Parkinson's disease). Swallowing is
      regulated by the vagus nerve and glossophayngeal nerve via secretion of substance
      P, and the amount of substance P secretion depends on the content of dopamine in
      the basal nucleus. Therefore, dopamine supplement drugs (e.g., L-dopa or
      amantadine hydrochloride), and agents to block substance P degradation (e.g.,
      angiotensin-converting enzyme) are effective in the treatment of eating
      disorders. Thus, these indicate that we require an understanding of
      neuropsychopharmacology for the development of new medical treatments for eating
      and swallowing disorders.

PMID- 20030189
TI  - [Determinants of chilliness among young women and their application to
      psychopharmacological trials].
AB  - Chilliness is a common complaint among menopausal women. Increasing evidence
      indicates that young women also suffer from chilliness, resulting in decreased
      learning, motivation, and concentration. Neither diagnostic criteria nor drug
      therapies exist for chilliness, and thus, young women suffer from insomnia,
      fatigue, and mood disturbance. Because chilliness is correlated with hormonal
      changes observed during premenstrual, postpartum, and menopausal periods,
      reproductive hormones are likely involved. Recently, we elucidated methodological
      issues related to identifying young women with chilliness. We used a new
      questionnaire to determine complaint severity with regard to chills and assessed
      physical parameters (BMI, body fat ratio, basal metabolism, blood pressure),
      peripheral circulation, and recovery of skin surface temperature after mild cold
      water finger immersion. Using a discriminant analysis (hit ratio, 84.5%), we
      demonstrated that four parameters (blood flow, difference between underarm and
      surface temperature, recovery rate after mild cold exposure, and score for
      chilliness-related complaints) were important determinants of chilliness. Among
      traditional candidate substances for alleviating chilliness, Piper longum and
      royal jelly showed significant effects. Additionally, we investigated seasonal
      change in the experience of chilliness and found that young women suffer from
      chilliness during the summer. These findings have important implications for
      understanding chilliness in women.

PMID- 20030190
TI  - [Research progress in neuropsychopharmacology updated for the post-genomic era].
AB  - Neuropsychopharmacological research in the post genomic (genomic sequence) era
      has been developing rapidly through the use of novel techniques including DNA
      chips. We have applied these techniques to investigate the anti-tumor effect of
      NSAIDs, isolate novel genes specifically expressed in rheumatoid arthritis, and
      analyze gene expression profiles in mesenchymal stem cells. Recently, we have
      developed a novel system of quantitative PCR for detection of BDNF mRNA isoforms.
      By using this system, we identified the exon-specific mode of expression in acute
      and chronic pain. In addition, we have made gene expression profiles of KO mice
      of beta2 subunits in acetylcholine receptors.

PMID- 20030191
TI  - [What I have learned and accomplished through research on multiple sclerosis
      (MS)].
AB  - Multiple sclerosis is an inflammatory demyelinating disease of the central
      nervous system (CNS). This disease is characterized by so-called "multiplicity in
      time and space in the CNS". Although the pathomechanisms of MS have been
      extensively studied for a long time, the etiology is still unknown. It has been
      pointed out that the prevalence rate of MS is very low, and that the optic spinal
      form of MS (OSMS), which mainly affects the optic nerves and spinal cord, is
      common in Japan. There has been a long controversy as to the differences between
      OSMS and neuromyelitis optica (NMO), and whether NMO or OSMS is a subtype of
      multiple sclerosis (MS) or a distinct disease. Recently, a highly disease
      specific autoantibody, NMO-IgG, was found in the sera of patients with NMO as
      well as OSMS. However, this antibody was not detected in the sera of MS patients.
      Therefore, we conclude that OSMS is the same as NMO, and speculate that NMO/OSMS
      may be a distinct disease from MS. Many investigations have revealed several
      differences clinically and pathologically between MS and NMO/OSMS. The following
      features such as female predominance, no brain lesions and longitudinally
      extended spinal cord lesions by MRI study and neuropathologically necrotic or
      cavitary lesions are commonly seen in NMO/OSMS. The most recent and important
      discovery that NMO-IgG reacts specifically with aquaporin 4 (AQP4), which is a
      water channel localized in astrocytes, opened new avenues for understanding the
      pathogenesis of NMO/OSMS. We immunocytochemically studied the expression of AQP4
      in lesions of postmortem NMO/OSMS, and found that AQP4 was completely lost in the
      acute lesions. In addition, an astrocytic marker, GFAP, was also lost in the
      NMO/OSMS lesions. However, the myelin basic protein-stained fibers were
      relatively preserved. These immunocytochemical features are in contrast to those
      of MS. In MS, there was no loss of either AQP4 or GFAP expression in the lesions.
      Moreover, the values of GFAP were markedly increased in CSF from patients with
      NMO/OSMS in the acute phase but were never increased in patients with MS. These
      results strongly suggest that astrocytic impairment associated with AQP4 antibody
      may be mainly involved in NMO, and that the pathogenesis of NMO is distinct from
      MS, which is primarily a demyelinating disease.

PMID- 20030192
TI  - [Rescue treatments for multiple sclerosis].

PMID- 20030193
TI  - [Clinical and pathological topics of multiple sclerosis].
AB  - Therapeutic options for patients with progressive multiple sclerosis are
      currently limited. This is in part due to lack of knowledge regarding the
      pathophysiology of the disease in this stage. This review summarizes recent
      findings, showing profound differences in the pathology between relapsing and
      progressive MS. Pathological hallmarks in progressive MS are slow expansion of
      pre-existing white matter lesions, massive cortical demyelination and extensive
      diffuse injury of the normal appearing white matter. As in relapsing MS also in
      progressive MS active tissue injury is invariably associated with inflammation,
      but inflammation seems to be trapped behind a closed blood brain barrier.
      Different immunological mechanisms are involved in tissue destruction in
      progressive MS, but inflammation induced mitochondrial injury appears to be a
      dominant pathway. Future therapeutic interventions will have to target
      inflammation, which is compartmentalized in the central nervous system. In
      addition, however, neuroprotective therapies may be necessary.

PMID- 20030194
TI  - [Fine structure of neuronal and glial processes in neuropathology, a personal
      historical note].
AB  - Neurons and glia are characterized by their well formed processes and by cell-to
      cell relationships. Neurons show cylindrical processes, which form synaptic
      junctions. On the other hand, the peripheral parts of the glial cells are sheet
      like in nature. Thus, the oligodendroglial cells form shovel-shaped myelin sheets
      around axons. The astrocytes also form delicate sheet-like processes, which
      separate the central nervous system from the mesodermal tissue and surround
      neuronal soma, dendrites and synapses. Fine structural studies in
      neuropathological material provide many interesting new findings on neuronal and
      glial processes. This communication highlights my exciting experience studying
      neuropathology for over 50 years.

PMID- 20030195
TI  - [The Japanese Society of Neurology. In commemoration of the 50th anniversary of
      the founding].
AB  - In the last nineteenth century, Japan produced two pioneers in the neurological
      field. Perhaps Prof. Hiroshi Kawahara's most monumental contribution was the
      first publication of the textbook of neurology in Japan. He first reported the
      two-brother cases of bulbar and spinal muscular atrophy of X-linked recessive
      trait Kinnosuke Miura, the professor of the University of Tokyo, described the
      endemic disease of the "kubisagari" (head-dropping). He published a paper of
      clinical and pathological study on amyotrophic lateral sclerosis. In 1902, Miura
      founded the "Japanese Society of Neurology" together with Shuzo Kure, the
      professor of Psychiatry of the University of Tokyo. This Society underwent a
      metamorphosis to an organization mainly composed of psychiatrists, because of a
      steady increase in membership of psychiatrists. In the mid-nineteenth century,
      neurological activities were restricted within the departments of internal
      medicine, psychiatry or neurosurgery. After the end of World War II, neurology
      came to receive recognition of the identity. In 1960, Seizo Katsunuma, the
      professor of Nagoya University, and Shigeo Okinaka, the professor of the
      University of Tokyo, started anew "the Japanese Society of Neurology", which was
      independent of the former Society founded in 1902. In this paper, the outlines of
      the history and development of the former and the present Japanese Societies of
      Neurology for these one hundred years are presented.

PMID- 20030196
TI  - [Independent action of the Japanese Society of Neurology is a driving force
      behind the development of Japanese neurology].
AB  - The Japanese Society of Neurology was founded in 1960. The Department of
      Neurology was established at The Kyushu University Faculty of Medicine in 1963,
      and then The Japanese Neurology has advanced.

PMID- 20030197
TI  - [Development of Japanese neurology in the last half century: a global
      perspective].
AB  - The Japanese Society of Neurology, founded in 1960, suffered an initial set back
      internationally primarily because of the language barrier. It gained a quick, and
      justifiable recognition after the 12th World Congress of Neurology held in Kyoto
      (1981), and now enjoys an indisputable reputation in the field of neuroscience.
      Clinical neurophysiology lead the world from the inception with the early
      formation of study group in 1951 as the predecessor of the current Japanese
      Society of Clinical Neurophysiology. In both fields, however, clinical training
      has fallen behind research achievements with limited resources and a shortage of
      teaching staff. On the occasion of 50th anniversary of our society, we must seek
      the sovereignty of neurology as an independent discipline as advocated by the
      World Federation of Neurology. We must also participate in global affairs with
      confidence despite a perceived language barrier to promote neurology world wide.

PMID- 20030198
TI  - [Development of neurology in Japan and its contribution to elucidate and resolve
      the sociomedical problems].
AB  - Japanese Society of Neurology (JSN) was established in 1960 with 643 members, and
      in 2009 it has grown up to a big society having more than 8,000 members including
      3,600 neurology board specialists. JSN has greatly contributed in elucidating and
      resolving many socio-medical problems. I will take three topics including SMON
      (subacute myelo-optico-neuropathy), infectious Creutzfeldt-Jakob disease (CJD)
      and Minamata disease. SMON was a new epidemic disease characterized by subacute
      optic neuritis and myeloneuropathy associated with diarrhea and abdominal
      symptoms. The research committee clarified that it was a neurological
      complication of chinoform, a drug for gastroenteritis. CJD surveillance started
      in 1996 for variant CJD, and uncovered many patients who developed CJD after
      human dura draft. The government prohibited to use non-inactivated human dura.
      Minamata disease is an organic mercury poisoning of people who took fish
      contaminated by mercury in Minamata bay in Kumamoto or in Aganogawa river in
      Niigata. The factories discharged water contaminated with mercury which was
      accumulated in fish and shellfish. Still many victims claim for compensation to
      the companies and government. Neurologists in Kumamoto and Niigata greatly
      contributed to diagnose and treat the victims and to clarify the cause of the
      disease.

PMID- 20030199
TI  - [Certification for specialists on neurology by Japanese Society of Neurology].
AB  - In accordance with recent ever increasing numbers in elder population in Japan,
      number of patients of age-related neurological diseases such as stroke, dementia
      and neurodegenerative diseases, etc., also remarkably increasing. Naturally,
      social needs for medical intervention in neurological fields inevitably become
      indispensable. The role of the neurologists, especially specialists of neurology,
      must be substantially important in the near future. The Japanese Society of
      Neurology has already launched the system for quality-certified specialists for
      neurology in 1970's. The aim of the system to educate and certify specialists for
      neurology has been announced as follows; the specialist of neurology must widely
      experienced and practiced in clinical fields, and must properly diagnose and
      judge the neurological illness even they are so complicate and difficult to
      manage (Rinsho Shinkeigaku (Clinical Neurology) 38 (6): 593-619, 1998). However,
      in future, the specialists for neurology must cultivate and keep the minds of
      "Professionalism" of physicians as well as their skills for clinical neurology.
      The Professionalism consists of altruism, accountability, excellence, duty, honor
      and integrity, respect and a personal commitment to life-long learning (ABIM:
      American Board of Internal Medicine, Project Professionalism, 1990-). The
      specialists of neurology with recent privilege in clinical insurance system for
      their special ability and techniques for neurological examination, should not
      only share their clinical specialty but also provide their opinion based upon
      Professionalism to all over the world.

PMID- 20030200
TI  - [Molecular-targeted therapy for neurodegenerative diseases].
AB  - Neurodegenerative diseases have been construed as incurable disorders. However,
      therapeutic development for these diseases is now facing a turning point:
      analyses of cellular and animal models have provided insights into pathogenesis
      of neurodegenerative diseases, and have indicated rational therapeutic approaches
      to them. Therefore, how to realize molecular targeted therapy for
      neurodegenerative diseases is becoming one of the most challenging issues in the
      clinical neurology. Primarily, pathophysiological understanding of the disease
      from basic science is the first step. For the successful clinical trials,
      effective trial design, sufficient economic and social support, and education are
      indispensable. The development of androgen deprivation therapy for spinal and
      bulbar muscular atrophy (SBMA) is a representative study in this field. SBMA is a
      hereditary neurodegenerative disease caused by expansion of a trinucleotide CAG
      repeat in the first exon of the androgen receptor (AR) gene. There is increasing
      evidence that testosterone, the ligand of AR, plays a pivotal role in the
      neurodegeneration in SBMA. The striking success of androgen deprivation therapy
      in SBMA mouse models has been translated into phase 2, and then phase 3, clinical
      trials.

PMID- 20030201
TI  - [Molecular mechanism for spinocerebellar ataxias].
AB  - Recent advance of molecular biology reveals that quality control of intracellular
      environment takes an important role for maintaining the neuronal function. One is
      a quality control of protein and another is a quality control of nucleotide.
      Polyglutamine disease is a disease which caused by a failure of quality control
      of protein. Expanded polyglutamine repeats result in neurodegenerative disorders,
      but their cytotoxic structures remain to be elucidated. About the quality control
      of nucleotide in neuron, DNA single-strand breaks (SSBs) were continually
      produced by endogenous reactive oxygen species or exogenous genotoxic agents.
      These damaged ends posses damaged 3'-ends including 3'-phosphate, 3'
      phosphoglycolate, or 3'-alpha, beta-unsaturated aldehyde ends, and should be
      restored to 3'-hydroxyl ends for subsequent repair processes. We have
      demonstrated by in vitro assay that aprataxin, the causative gene product for
      early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ ataxia with
      oculomotor apraxia type 1 (EAOH/AOA1), specifically removes 3'-phosphoglycolate
      and 3'-phosphate ends at DNA 3'-ends, but not 3'-alpha, beta-unsaturated aldehyde
      ends. The findings indicate that aprataxin removes blocking molecules from 3'
      ends, and that the accumulation of unrepaired SSBs with damaged 3'-ends underlies
      the pathogenesis of EAOH/AOA1. The findings will provide new insight into the
      mechanism underlying degeneration and DNA repair in neurons.

PMID- 20030202
TI  - [Studies of gene therapy for Parkinson's disease].
AB  - Currently, four Phase I clinical trials are underway utilizing recombinant adeno
      associated viral (rAAV) vectors for the treatment of Parkinson's disease. The
      vehicle used mainly for gene delivery to the human brain is rAAV vector, which is
      non-pathogenic and non-self-amplifying. At present, the gene therapy approach is
      not the best way for the treatment of PD patients, but we believe that the
      further progress is anticipated toward making this strategy a therapeutic option
      for PD in the future. This article will review currently ongoing clinical trials
      of PD gene therapy and then introduce our studies about the gene therapy for PD.

PMID- 20030203
TI  - [Approach of gene medical treatment in neurological diseases with the
      neurologist's. "Approach of support to the patients with inherited and incurable
      neurological diseases"].
AB  - Advancements in medical genetics have increased access to genetic diagnosis in
      clinical neurology and accompanying genetic counseling. However, its use has not
      yet spread and the frequency of general biochemistry inspection in medical
      treatment and by patients remains low. Many problems remain for doctors, though
      sociocultural and other various causes exist. Thus, a network of care specialists
      for inherited and incurable neurological diseases has been established,
      consisting of multi-occupational categories in medical treatment, health, and
      welfare such as clinical inheritance specialists, psychiatrists, public health
      nurses, and medical social workers, to meet the rise in availability of such
      methods. Businesses in areas such as training, consultation, and field research
      have arisen. An educational campaign for neurologists who have taken a central
      role in treatment of inherited and incurable neurological diseases, and related
      information have been disseminated to those working in fields related to regional
      welfare of neurological medicine, and patients are now supported totally by team
      and regional counseling. These new developments in support systems for inherited
      and incurable neurological diseases, have steadily achieved the respective goals.
      We aim to promote its evolution to a more advanced network to promote the
      independence of individual patients in the future.

PMID- 20030204
TI  - [Practical genetic counseling and testing in clinical neurology].

PMID- 20030205
TI  - [Becoming a professional neurologist].

PMID- 20030206
TI  - [New international classification of epilepsy and new antiepileptic drugs for
      medically intractable epilepsy].
AB  - The task force of the international league against epilepsy (ILAE) proposed the
      "Diagnostic scheme for people with epileptic seizures and epilepsy" in 2001. The
      2001 diagnostic scheme was updated in 2006. The ILAE Core Group recommended the
      new classification to replace the previous one (ILAE, 1981, 1989). However, the
      new classification is too complex to use for clinicians except expert
      epileptologists. About 10 new antiepileptic drugs are launched recently. Among
      them, gabapentine, topiramate, and lamotrigine have been approved in Japan as
      adjunctive therapy for medically intractable seizures. The advantage of the new
      antiepileptic drugs includes newer mechanism of action, broad spectrum of anti
      seizure effects, fewer side effects, and lesser drug interactions. The rational
      polytherapy is necessary for refractory epilepsy. The majority of elderly
      patients with new onset epilepsy become seizure free on antiepileptic
      monotherapy, often with modest dose. We are now in the new era of epilepsy
      treatment.

PMID- 20030207
TI  - [Unique clinical features and pathophysiology of anti-NMDA receptor
      encephalitis].
AB  - Recently a new category of treatment-responsive encephalitis has been proposed
      associated with antibodies against neuronal cell membrane antigens, including
      VGKC, NMDA receptor (NMDAR) and AMPA receptor. Anti-NMDAR encephalitis is caused
      by the antibodies, which bind to extracellular conformal epitope in the NR1/NR2
      heteromers of the NMDAR. The antibodies are usually detected in CSF/serum of
      young women with ovarian teratoma (OT), who typically developed schizophrenia
      like psychiatric symptoms. Most patients developed seizures, followed by
      unresponsive/catatonic state, central hypoventilation, and bizarre orofacial-limb
      dyskinesias. Based on symptomatology and current NMDAR hypofunction hypothesis in
      schizophrenia, we speculated that the antibodies might cause inhibition of NMDAR
      in presynaptic GABAergic interneurons, causing a reduction of release of GABA.
      This results in disinhibition of postsynaptic glutamatergic transmission,
      excessive release of glutamate in the prefrontal/subcortical structures, and
      glutamate/dopamine dysregulation. Recent studies demonstrated that the antibodies
      cause reversible reduction in the numbers of cell-surface NMDAR and NMDAR
      clusters in postsynaptic dendrites, suggesting antibodies-mediated decreased
      function of NMDAR. Early tumor resection with immunotherapy is recommended in OT
      positive cases but not in OT-negative cases. However, exploratory laparotomy may
      increase the chance to identify microscopic teratoma and improve the outcome if
      patients who were refractory to immunotherapy had anti-NMDAR antibodies and
      ovarian cyst.

PMID- 20030208
TI  - [The mechanism and control of neuropathic pain].
AB  - Neuropathic pain is a debilitating pain that occurs after nerve injury and is
      generally resistant to currently available treatments including morphine. Such
      pain involves aberrant excitability in dorsal horn neurons after nerve injury.
      Emerging evidence indicate that the enhanced activity of dorsal horn neurons
      requires a communication with microglia. Results of our laboratory have shown
      that activating P2X4R upregulated in spinal microglia after nerve injury
      contributes to neuropathic pain through a release of BDNF from microglia, which
      is a crucial factor to signal to dorsal horn neurons to cause neuronal
      hyperexcitability. Activated spinal microglia also express P2Y12R, and P2Y12R-KO
      mice display impaired neuropathic pain. The mechanisms of microglia activation
      are unknown, but our recent study shows that interferon-gamma (IFN-gamma) can be
      an important factor that causes spinal microglia activation after nerve injury.
      IFN-beta upregulates P2X4R in microglia and causes P2X4R-dependent allodynia.
      These findings suggest that purinoceptors in spinal microglia is crucial for
      pathological intractable pain.

PMID- 20030209
TI  - [TDP-43 proteinopathies, toward understanding of the molecular pathogenesis].
AB  - The TDP-43 proteinopathies: Toward understanding of the molecular pathogenesis.
      TAR DNA binding protein of 43 kDa (TDP-43), a heterogeneous nuclear
      ribonucleoprotein was identified as a major component of ubiquitin-positive
      inclusions in FTLD and ALS, and the concept of TDP-43 proteinopathies was
      proposed. Immunoblot and immunohistochemical analyses using multiple anti
      phosphorylated TDP-43 antibodies revealed that hyperphosphorylated 18-26 kDa C
      terminal fragments in addition to the full-length TDP-43 are major constituents
      of inclusions in FTLD-U and ALS. Recent discovery of mutations in the TDP-43 gene
      in familial and sporadic ALS, indicating that abnormality of TDP-43 protein cause
      neurodegeneration. It also strongly suggests that aggregation of TDP-43 or the
      process is responsible for neurodegeneration in FTLD-U and ALS. To investigate
      the molecular mechanisms of aggregation of TDP-43, we have established two
      cellular models for intracellular aggregates of TDP-43 similar to those in brains
      of TDP-43 proteinopathies patients. The first consists of SH-SY5Y cells
      expressing mutant TDP-43 that lacks both the nuclear localization signal (NLS)
      and residues 187-192 (deltaNLS & 187-192). The second model consists of SH-SY5Y
      cells expressing an aggregation-prone TDP-43 C-terminal fragment as a green
      fluorescent protein (GFP)-fusion. In these cells, round structures positive for
      both anti-pS409/410 and anti-Ub are observed. These results suggest that
      intracellular localization of TDP-43, truncation of TDP-43 and proteasomal
      dysfunction of cells may be involved in the pathological process of TDP-43
      proteinopathies. We also found that two small compounds that have been reported
      to be beneficial in phase II clinical trials of Alzheimer's disease, inhibited
      the formation of TDP-43 aggregates in these two cellular models, suggesting that
      these compounds may be effective for the treatment of ALS and FTLD-U.

PMID- 20030210
TI  - [Regulation, structure and function of brain aquaporin].
AB  - Discovery of aquaporin water channel proteins has provided insight into the
      molecular mechanism of membrane water permeability. In mammalian brain, Aquaporin
      4 (AQP4) is the main water channel and is distributed with highest density in the
      perivascular and subpial astrocyte end-feet. AQP4 is a critical component of an
      integrated water and potassium homeostasis. Indeed, AQP4 has been implicated in
      several neurologic conditions, such as brain edema, seizure and even mood
      disorders. Expression and regulation of AQP4 have been studied to understand the
      roles of AQP4 in physiological and pathological conditions. Here we discuss about
      the mechanisms how AQP4 is dynamically regulated at different levels; channel
      gating, subcellular distribution, phosphorylation, protein-protein interactions
      and orthogonal array formation. Interestingly, AQP4 has been identified as a
      target antigen of autoimmune attack in neuromyelitis optica (NMO). We have
      evaluated putative epitopes on AQP4 for NMO-IgG binding. We have also studied
      Drosophila Big Brain (Bib), since Bib has high sequence homology to AQP-4, and
      play an important role for Drosophila neurogenesis. AQP4 may be a potential
      therapeutic target in several neurologic conditions. Further studies from
      different aspects are required to develop new drugs against AQP4.

PMID- 20030211
TI  - [Recent advance in research for myasthenia gravis, in relation to various
      antibodies affecting synaptic structure and function].
AB  - Autoantibodies impair acetylcholine receptor (AChR) in myasthenia gravis (MG) and
      P/Q-type voltage-gated calcium channel (VGCC) in Lambert-Eaton myasthenic
      syndrome (LEMS). (1) Some of MG and LEMS patients are "seronegative" for
      respective antibodies or modified by antibodies that recognize other proteins
      than AChR and VGCC such as MuSK, AChR allosteric site, membrane Na+ channel and
      ryanodine receptor-1 (RyR1) in MG, and synaptotagmin-1 in LEMS. (2) Autoimmune
      responses affect the proteins participating in the mechanisms to compensate for
      synaptic disorders on the basis of presynaptic Ca2+ homeostasis provided by VGCC
      and non-VGCC (receptor-operated TRPCs): they act as enhancers of Ca(2+) -mediated
      ACh release via phospholipase C signaling pathways including M1-type presynaptic
      muscarinic AChR, neurotrophin receptor (TrkB), and fast-mode of synaptic vesicle
      recycling. (3) The pathophysiology contributive to contractile fatigue in MG
      includes RyR1 and also TRPC3. The TRPC3 also forms a complex with STIM1 and Orail
      to make up for Ca2+ after sarcoplasmic Ca2+ release. The prevalent detection of
      anti-TRPC3 antibodies in MG with thymoma could affect muscle contractile
      machineries in addition to anti-RyR1-induced affection. (4) When one faces
      "seronegative" MG, one should be cautious to conformation-specific antibodies and
      also congenital myasthenic syndromes.

PMID- 20030212
TI  - [Conscious awareness of cognitive processes and their dysfunction].
AB  - Conscious awareness is the state in which external and internal stimuli are
      perceived and can be intentionally acted on. Although various investigations have
      provided new insights into the neural mechanisms of conscious awareness, its
      whole network in human remains to be solved. Anosognosia for visual dysfunction
      and unconscious processing of visual stimuli are good examples of dissociation
      between cognitive processes and conscious awareness. Anton syndrome, anosognosia
      for blind or deaf, could be observed in blindness caused by cerebral as well as
      ophthalmological diseases, when general cognitive function or attention is
      impaired. Unawareness of hemianopia is not an exception but a common phenomenon,
      which seems to be related to a completion phenomenon and macular sparing.
      Patients with visual agnosia are not consciously aware of the nature of their
      visual dysfunction but have a vague feeling of visual impairment. Blindsight,
      unconscious visual processing in the blind field, might be partly related to the
      dorso-dorsal visual stream that takes roles in the control of actions "on line"
      without awareness of spatial perception. In patients with unilateral spatial
      neglect, unconscious processing of visual stimuli on the neglected space was also
      observed. Better understanding of neural mechanisms of conscious awareness would
      provide insights into various neurological disorders and therapeutic approaches.

PMID- 20030213
TI  - [Mechanism underlying thrombus formation in cerebral infarction].
AB  - For thrombus formation, three important factors, blood flow, blood component and
      blood vessels, have been recognized as Virchow's triad. In cardiogenic embolism
      with atrial fibrillation, stagnation of blood in the left atrium causes fibrin
      rich thrombus. Anticoagulation is the only effective drug for prevention of this
      type of thrombus. In atherothrombotic and lacunar infarction, injury of
      endothelium and arterial vessels and platelet play a crucial role of formation of
      platelet-rich thrombus. Antiplatelet drugs such as aspirin, clopidogrel and
      cilostazole are effective for prevention of arterial thrombus and stroke
      recurrence, but other drugs such as statin for plaque stabilization and
      improvement of endothelial function could be used to reduce the recurrence of
      ischemic stroke.

PMID- 20030214
TI  - [Intravenous rt-PA therapy for acute ischemic stroke: efficacy and limitations].
AB  - After the success of the 1995 National Institutes of Neurological Disorders and
      Stroke (NINDS) study using intravenous (i.v.) recombinant tissue plasminogen
      activator (rt-PA, alteplase) within 3 hours in acute stroke, this therapy was
      approved worldwide and has been a standard therapy for acute stroke patients. In
      Japan, IV alteplase at a dose of 0.6 mg/kg was approved in 2005 after a
      multicenter study using this low dose of alteplase (Japan Alteplase Clinical
      Trial [J-ACT]). IV rt-PA can drastically improve stroke outcomes. However, more
      than half of treated patients are not independent in the chronic stage. In
      addition, the therapeutic time window was so limited that many stroke patients do
      not have a chance to receive the therapy. In 2008, European Cooperative Acute
      Stroke Study III showed that IV rt-PA administered between 3 and 4.5 hours after
      stroke onset significantly improved clinical outcomes in stroke patients; the
      success resulted in the renewal of recommendation in guidelines in Europe,
      Canada, and the United States. Several therapeutic strategies, including
      endovascular therapy, sonothrombolysis, and neuroprotective therapy, may improve
      the efficacy of IV rt-PA.

PMID- 20030215
TI  - [Transcranial sonothrombolysis].
AB  - Transcranial ultrasonic diagnostic equipment has been approved to enhance the
      thrombolytic effect of IVrt-PA. Moreover, transcranial sonothrombolysis with low
      frequency ultrasound has a great advantage in lytic effect of IVrt-PA. It is
      remarkable to choose a optimal ultrasonic condition for transcranial
      sonothrombolysis. We are developing a new transcranial targeting Low Frequency
      Ultrasonic Thrombolysis system (TCT-LoFUT). This system is anticipated to be a
      useful therapeutic equipment to realize a early recanalization in the acute
      ischemic stroke treatment.

PMID- 20030216
TI  - [Endovascular treatment for ischemic cerebrovascular diseases].

PMID- 20030217
TI  - [Exploration of pathogenesis and therapy development for ALS employing sporadic
      disease model].
AB  - The mechanisms underlying motor neuron degeneration in amyotrophic lateral
      sclerosis (ALS) remain poorly understood even now 140 years after the first
      description of the disease in 1869 by Jean-Martin Charcot. Exploration of
      pathogenesis of ALS has long been dependent on transgenic animal models with
      mutations in the copper/ zinc superoxide dismutase 1 (SOD1) gene. However, the
      lack of therapeutic concordance between these animal models and human sporadic
      ALS patients is troubling. The reasons include that there might exist the
      differences of pathogenesis between sporadic and familial ALS and/or the disease
      models for sporadic ALS have not been established. We have been working on
      screening motor neuron-specific genes critical for pathogenesis of sporadic ALS
      using cDNA microarray and laser capture microdissection techniques. Many of the
      resultant genes are of intense interest and may provide a powerful tool for
      determining the molecular mechanisms of sporadic ALS. In particular, dynactin-1,
      a major component of dynein/dynactin complex and several cell cycle-related genes
      are the targets of our research. Development and analysis of new disease models
      for sporadic ALS based on these genes will open an avenue for novel therapeutics.

PMID- 20030218
TI  - [Development of motor neuron restorative therapy in amyotrophic lateral sclerosis
      using hepatocyte growth factor].
AB  - Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disorder
      characterized by the death of upper and lower motor neurons. Approximately 20% of
      familial ALS cases are caused by mutations in the superoxide dismutase 1 (SOD1)
      gene. Mutations in the fused in sarcoma/translated in liposarcoma (FUS/TLS) gene
      have been recently discovered to be associated with familial ALS. We found
      FUS/TLS mutations in familial ALS cases in Japan. Even in Asian races, ALS with
      FUS/TLS mutations may have common characteristics of early onset, rapid progress,
      high penerence trait. We developed rats that express a human SOD1 transgene with
      two different ALS-associated mutations (G93A and H46R) develop striking motor
      neuron degeneration and paralysis. The larger size of this rat model as compared
      with the ALS mice will facilitate studies involving manipulations of spinal fluid
      (implantation of intrathecal catheters for chronic therapeutic studies; CSF
      sampling) and spinal cord (e.g., direct administration of viral- and cell
      mediated therapies). Hepatocyte growth factor (HGF) is one of the most potent
      survival-promoting factors for motor neurons. To examine its both protective
      effect on motor neurons and therapeutic potential, we administered human
      recombinant HGF (hrHGF) by continuous intrathecal delivery to G93A transgenic
      rats at onset of paralysis for 4 weeks. Intrathecal administration of hrHGF
      attenuates motor neuron degeneration and prolonged the duration of the disease by
      63%. Our results indicated the therapeutic efficacy of continuous intrathecal
      administration of hrHGF in ALS rats. In addition, HGF is capable of reducing
      astrocytosis and microglial accumulation, and thus supports the attention of a
      glial-dependent mechanism of ALS progression. These results should prompt further
      clinical trials in ALS using continuous intrathecal administration of hrHGF.

PMID- 20030219
TI  - [Future perspectives of immunotherapy against ALS].
AB  - Emerging evidence suggests that misfolded proteins in the various
      neurodegenerative diseases can be targets for immunotherapy including vaccination
      antibody therapy. To date, vaccination strategies have been shown to be effective
      in Alzheimer's disease, Parkinson's disease, Huntington's disease and Prion
      disease. Interestingly, the subcellular localization of the target proteins
      varies, including cytosol, synaptosomes and extracellular spaces. We have
      documented that mutant SOD1 is secreted together with a neurosecretory protein
      chromogranin, and that vaccination against the SOD1 mutant is beneficial in
      delaying the onset and prolonging the lifespan. However, the mechanism of
      vaccination on the mutant SOD1 mice remains unclear. Moreover, vaccination
      induces diverse inflammatory reactions, which are reported to modify both the
      onset and the progression of ALS. Therefore, it is important to clarify the role
      of innate or acquired immunity in the pathogenesis of ALS to avoid the adverse
      reactions of the vaccination, and rather to apply it for amelioration. Passive
      immunization is also promising since only aberrant proteins can be targeted using
      a specific monoclonal antibody. The development of the current immunization
      techniques is very important for the future application, since key molecules for
      the sporadic ALS have emerged and are intensively investigated such as TDP-43.

PMID- 20030220
TI  - [Gene therapy of ALS with RNA interference].
AB  - RNA interference (RNAi) is the process of sequence-specific, post-tanscriptional
      gene silencing, initiated by double-stranded RNA (dsRNA). The gene therapy for
      familial ALS with siRNA had been started and showed promising results in the
      model mouse. There is a recent progress in the delivery of siRNA to the central
      nervous system. There are still important problems for application of gene
      therapy including off-target effect and gene delivery of siRNA, but a rapid
      progress can be expected because of the extremely high efficiency of siRNA.

PMID- 20030221
TI  - [Regeneration of the central nervous system using iPS cell-technologies].
AB  - Induced pluripotent stem (iPS) cells are pluripotent stem cells directly
      reprogrammed from cultured mouse fibroblast by introducing Oct3/4, Sox2, c-Myc,
      and Klf4. Cells obtained using this technology, which allows the ethical issues
      and immunological rejection associated with embryonic stem (ES) cells to be
      avoided, might be a clinically useful source for cell replacement therapies. We
      found that secondary neurospheres (SNSs) generated from various mouse iPS cell
      showed their neural differentiation capacity and teratoma formation after
      transplantation into the brain of immunodeficient NOD/SCID mice. We found that
      origin (source of somatic cells) of the iPS cells are the crucial determinant for
      the potential tumorigenicity of iPS-derived neural stem/progenitor cells and that
      their tumorigenicity results from the persistent presence of undifferentiated
      cells within the SNSs. Surprisingly, SNSs derived from c-Myc minus iPS cells
      generated without drug selection showed robust tumorigenesis, in spite of their
      potential to contribute adult chimeric mice without tumor formation. Furthermore,
      we examined whether the transplantation of non-tumorigenic Nanog-iPS-derived SNSs
      into mouse spinal cord injury (SCI) model could promote locomotor function
      recovery. As a result, we found that properly pre-evaluated iPS clone-derived
      neural stem/progenitor cells may be a promising cell source for future
      transplantation therapy of SCI.

PMID- 20030222
TI  - [Preservative therapies of injured central nervous system by gene transfer].
AB  - The central nervous system (CNS) injury causes severe loss of functions, and the
      development of therapies to recover the functions can be an important target. The
      present study highlighted the preservation-oriented therapy by transferring genes
      to the injured neurons. To identify therapeutic targets for the preservative
      therapies of injured CNS, we focused on clarifying the mechanism underlying the
      degeneration and regeneration of neurons after injuries using nerve injury models
      of animals. We have identified several genes, some of which were the survive
      promoting and others were death-promoting molecules. In addition another subset
      of genes were assumed to be associated with promoting nerve regeneration. The
      single expression of variety of molecules by a viral vector was proved to have
      the potential to rescue and recover, and this was also confirmed in CNS injury
      model. We assumed that the most important issue was the balance of levels between
      the pro-survive and pro-death molecules, which expressed in response to nerve
      injury. Those suggest that variety of molecules could be a therapeutic target for
      neurodegenerative disease as well as the neuron protection after traumatic
      injury. Combining both the transplantation-oriented and the preservation-oriented
      strategies would give us more potent therapeutic possibilities.

PMID- 20030223
TI  - [Endogenous repair mechanisms in the brain].
AB  - Most of neurons are generated by neural stem cells in the developing brain at the
      embryonic or neonatal stages. However, recent studies indicate that adult brain
      also contains neural stem cells that continuously generate new neurons.
      Neurogenesis can be observed in the adult subventricular zone (SVZ) at the
      lateral wall of the lateral ventricles of various animal species including
      primates. Young neurons generated in the SVZ migrate over long distances and
      mature after they reach their final destinations where they function. In this
      talk, I will present our recent studies using animal models on the mechanisms of
      neuronal production, migration and maturation in the adult brain under
      physiological and pathological conditions, and discuss the possibility of their
      application into regeneration therapies for ischemic brain diseases.

PMID- 20030224
TI  - [Future of stem cell therapy for neuronal regeneration].
AB  - Embryonic stem (ES) cells are expected as promising donor cells for cell
      transplantation therapy. For example, mouse or monkey ES cell-derived dopamine
      (DA) neurons can survive in the brain and relieve Parkinson's disease (PD)
      symptoms in rat or monkey models. In 2001 and 2003, the results of a double-blind
      trial of the transplantation of human embryonic DA neurons into patients with PD
      were reported. These results teach us two things. First, cell transplantation has
      been clinically proven to be effective as a treatment for PD, although the
      effects are still far from optimal. Second, several problems remain to be solved,
      including patient selection, optimal donor cell volume, targeting of injection,
      immunosuppression, and control of dyskinesia. DA neurons have also been generated
      from several human ES cell lines. Furthermore, functional recovery of rat PD
      models after transplantation was observed. One of the major problems in ES cell
      transplantation is tumor formation, which is caused by a small fraction of
      undifferentiated ES cells in the graft. So, it is essential for undifferentiated
      ES cells to be eliminated from the graft for clinical application. These efforts
      will lead to clinical application of ES cell transplantation to the patients with
      PD.

PMID- 20030225
TI  - [Pre-symptomatic detection of Alzheimer's disease and mild cognitive impairment].
AB  - The clinical diagnosis of Alzheimer's disease (AD) is occasionally imprecise
      using consensus criteria for probable AD. Therefore, there is a great need for
      simple biomarkers that substantially aid early diagnosis and tract disease
      progression of AD and mild cognitive impairment. Of currently available
      biomarkers for AD, imaging markers are of particular importance based on their
      low invasiveness and reproducibility. In vivo detection of brain amyloid burden
      using positron emission tomography either by PIB or BF-227 would be quite
      attractive. In Japan, Alzheimer's disease neuroimaging initiatives (ADNI) has
      been launched in 2008 in accordance with US- and World-Wide ADNI. The paradigm of
      AD diagnosis and treatment would be shifted from "cognitive-based" to "biomarker
      based" framework. The use of ideal biomarkers can remarkably speed up AD drug
      discovery by providing earliest signals of drug efficacy.

PMID- 20030226
TI  - [Early diagnostic biomarker for Alzheimer's disease now and in the future].
AB  - Alzheimer's disease is thought to be "common disease". It is expected that new
      biological diagnostic marker will be discovered for Alzheimer's disease. There
      are two roles in diagnostic biomarker for AD.: one is a screening and the other
      one is to help definite diagnosis for AD. Simple screening method using touch
      panel type computer (Forgetfulness consultation program) is most useful of
      screening tools and phosphorylated tau protein in cerebrospinal fluid is highly
      appreciated as a diagnostic biomarker to help definite diagnosis. Serum WGA
      binding transferrin in AD is significantly higher than that in controls and high
      levels of it proceed increased levels of amyloid beta protein. Serum WGA binding
      transferrin may be useful for early diagnostic biomarker in serum.

PMID- 20030227
TI  - [Alzheimer's disease treatment by inhibition/modulation of the gamma-secretase
      activity].
AB  - Several lines of evidence indicate that the production and deposition of amyloid
      beta peptides (Abeta) contribute to the etiology of Alzheimer's disease.
      Inhibition or modulation of gamma-secretase, that is a responsible enzyme for the
      Abeta production, is one of the plausible therapeutics for Alzheimer's disease.
      However, the gamma-secretase is an unusual aspartic protease that cleaves the
      scissile bond within the transmembrane domain of several membrane protein
      including APP and Notch receptor. Thus, development of drugs that regulate the
      production of Abeta without affecting the Notch signaling is now demanding.
      Extensive drug screening and development allow that some secretase inhibitors and
      modulators have advanced into late-phase clinical trials, whereas the molecular
      mechanisms of Notch-sparing effect by these compounds effect still remain
      unknown. Identification of the molecular targets and mechanisms of these
      compounds using chemical biological approaches is currently underway. This review
      focuses on the recent development of inhibitors/modulators and provides a
      direction for the effective treatment of AD through inhibition/modulation of the
      gamma-secretase activity.

PMID- 20030228
TI  - [Vaccination therapy for Alzheimer's disease].
AB  - Since AN-1792 vaccine induced autoimmune encephalitis, several pharmaceutical
      companies are now concentrated in developing antibody therapy in Alzheimer's
      disease (AD). Each antibody has own characteristics. Thus, it is unpredictable at
      present which antibody is the most beneficial until we see the result of clinical
      trials. If disease modifying antibodies were found, they will be widely used for
      treatment of AD in near future. As a candidate of such antibodies, we have
      developed TAPIR-like antibody with much higher affinity to Abeta42 than Abeta40,
      and it effectively deleted senile plaque amyloid and Abeta oligomers without
      increasing microhemorrhages. Although passive immunization can avoid autoimmune
      encephalitis, it is expensive and it is not suitable for prevention. Thus, safe
      vaccines by active immunization would be better. Vaccines that induce Th2 type
      immune responses such as oral vaccine or per-nasal vaccine would be promising.

PMID- 20030229
TI  - [Development of therapy for distal myopathy with rimmed vacuoles].
AB  - Distal myopathy with rimmed vacuoles (DMRV), also called hereditary inclusion
      body myopathy, is an autosomal recessive disorder caused by homozygous or
      compound heterozygous missense mutations in GNE which encodes a protein with two
      enzymatic activities in sialic acid biosynthesis: UDP-GlcNAc 2-epimerase and
      ManNAc kinase. The disease starts from 1540 years and is slowly progressive. DMRV
      preferentially affects tibialis anterior and hamstrings muscles, and has
      characteristic findings in muscle pathology which include rimmed vacuoles,
      tubulofilamentous inclusions, deposition of amyloid, and phosphorylated tau. We
      generated DMRV mice (Gne -/- hGNE D176V-Tg) by crossmating Gne knock-out
      heterozygous mouse and human GNE p.D176V transgenic mouse. This model mouse
      recapitulates DMRV clinically, pathologically, and biochemically by developing
      muscle weakness and atrophy from 21 weeks, amyloid deposition from 31 weeks, and
      rimmed vacuoles and phosphorylated tau from 41 weeks while having lifelong
      hyposialylation. We gave three types of GNE metabolites, ManNAc, NeuAc and
      sialyllactose, to DMRV mice orally from 15 weeks until 55 weeks of age. Sialic
      acid supplementation almost completely precluded the disease and virtually no
      sign of DMRV was seen even at 55 weeks of age, indicating that decreased sialic
      acid is the cause of myopathic phenotype and sialic acid supplementation can
      prevent the disease process.

PMID- 20030230
TI  - [Exon skipping therapy for Duchenne muscular dystrophy by using antisense
      Morpholino].
AB  - Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin protein at
      the sarcolemma. Exon skipping by antisense oligonucleotides is a novel method to
      restore the reading frame of the mutated DMD gene, and rescue dystrophin
      production. We recently reported that systemic delivery of Morpholino antisense
      oligonucleotides targeting exon 6 and 8 of the canine DMD gene, efficiently
      recovered functional dystrophin proteins at the sarcolamma of dystrophic dogs,
      and improved performance of affected dogs without serious side effects (Yokota et
      al., Ann Neurol. 65 (6): 667-676, 2009). To optimize therapeutic antisense
      Morpholinos for more frequent mutations of the DMD gene, we designed antisense
      Morpholinos targeting exon 51 of the mouse DMD gene, and injected them separately
      or in combination into the muscles of mdx52 mice, in which exon 52 has been
      deleted by a gene targeting technique (Araki et al., 1997). We also tried
      systemic delivery of antisense Morpholino to skip exon 51 in mdx52 mice. It is
      important to verify the effectiveness and side effects of antisense Morpholino in
      experimental animal models such as dystrophic dogs or mdx52 mice, before clinical
      trials in DMD patients.

PMID- 20030231
TI  - [Pathomechanism and therapeutic strategy of Fukuyama congenital muscular
      dystrophy and related disorders].
AB  - Hypoglycosylation and reduced laminin-binding activity of alpha-dystroglycan are
      common characteristics of dystroglycanopathy, which is a group of congenital and
      limb-girdle muscular dystrophies. We previously identified the genes for Fukuyama
      congenital muscular dystrophy (FCMD) and muscle-eye-brain disease (MEB). FCMD,
      caused by a mutation in the fukutin gene, is a severe form of dystroglycanopathy.
      Knock-in mice carrying the founder retrotransposal insertion exhibited
      hypoglycosylated alpha-dystroglycan; however, no signs of muscular dystrophy were
      observed. More sensitive methods detected minor levels of intact alpha
      dystroglycan, and solid-phase assays determined laminin binding levels to be
      approximately 50% of normal. In contrast, intact alpha-dystroglycan is
      undetectable in the dystrophic Large mouse, and laminin-binding activity is
      markedly reduced. These data indicate that a small amount of intact alpha
      dystroglycan is sufficient to maintain muscle cell integrity in knock-in mice,
      suggesting that the treatment of dystroglycanopathies might not require the full
      recovery of glycosylation. Transfer of fukutin into knock-in mice restored
      glycosylation of alpha-dystroglycan. Transfer of LARGE produced laminin-binding
      forms of alpha-dystroglycan in both knock-in mice and the POMGnT1 mutant mouse.
      These data suggest that even partial restoration of alpha-dystroglycan
      glycosylation and laminin-binding activity by replacing or augmenting
      glycosylation-related genes might effectively deter dystroglycanopathy
      progression and thus provide therapeutic benefits.

PMID- 20030232
TI  - [Establishment of an evaluation method for muscular dystrophy and a patient
      registration system for clinical trials].
AB  - About 20 years have passed since the discovery of the causative protein of
      Duchenne muscular dystrophy, in 1987, and treatments targeting causative factors
      such as exon skipping, read-through of stop codons, and the upregulation of
      utrophin are approaching practical levels. In Japan, also, clinical trials are
      planned as the final stage of treatment development. In this field, an
      appropriate outcome measure has not been established due to the lack of
      experience in clinical trials. Treatments for muscular dystrophy are deemed
      effective only when increases in the muscle mass and muscle strength and
      improvements in the ADL and QOL as well as biological marker levels at target
      points have been demonstrated. The Muscular Dystrophy Clinical Study Group has
      addressed the development of these evaluation methods since 2002. Also, as
      treatments for muscular dystrophy being developed today are so-called tailor-made
      treatments aimed at specific mutations, a system that facilitates identification
      of the type and site of mutation in each individual must be prepared. The Gene
      Analysis Center was only just established in the National Center of Neurology and
      Psychiatry in 2009. Also, it is expected to be difficult to secure a sufficient
      number of subjects to start a clinical trial in a short period. Therefore, the
      Registry of Muscular Dystrophy (REMUDY), a system for the registration of
      patients with muscular dystrophy including their clinical and genetic information
      was implemented. This system, which provides information concerning the number of
      patients required by the protocol to researchers and pharmaceutical companies and
      the latest information regarding the development of treatments to patients, is
      expected to serve as a prototype for the establishment of the basis of clinical
      trials against rare diseases.

PMID- 20030233
TI  - [Establishment of the network of the severe intractacle diseases and the Center
      for Consulting and Assistance for Intractable Disorders].

PMID- 20030234
TI  - [Delivery of medical care to the neurological intractable diseases at home].
AB  - It is the case of the great difficulties for patients living with neurological
      intractable diseases to visit outpatient when the diseases are in the progressive
      stage. The national nursing care insurance was matured and the revised medical
      insurance system led to open the local supportive clinic for home care in 2006.
      It has set easier access to medical care at home. This is encouraging for
      patients who wish to continue to live with their families at their long time
      home. The medical care at home is where the attending physician has to
      demonstrate the expertise of how to assemble in- and out- interdisciplinary
      medical team. Moving a hospital room simply into at home does not made a medical
      care at home. You have to begin recognizing what gaps needed to fill in between a
      hospital room and at home. This is the area beyond what a family doctor single
      handedly deals with due to the nature of the diseases. The dual attending
      physician set-up is desirable including a family doctor and a specialist.

PMID- 20030235
TI  - [Disaster medical network for the patients with intractable disease-experiences
      of two large earthquakes].
AB  - Anti-disaster measures along with disaster medicine aims at reducing loss of
      property and life and facilitating grief work of the suffered people. In contrast
      the care system for patients with intractable disease has the same aim. According
      to the experiences of two large earthquakes including Chuetsu (2004) and Chuetsu
      oki earthquake (2007), earthquake-resistant buildings are necessary for
      maintaining hospital function as well as reviving community after occurrence of
      large earthquake. A list of patients living with ventilator and their individual
      care plan designed for disaster need to be prepared to transport each patient to
      the hospital at appropriate timing, when electricity and visiting nurse care
      system are damaged. Satellite telephone is very useful for communicating with
      such patients and medical teams because telephone connection is limited to only
      the specific calling number just after occurrence of earthquake.

PMID- 20030236
TI  - [Study and development of a new automatic suction system (SS) of intratracheal
      sputum in order to improve QOL of many patients with tracheostomy mechanical
      ventilation (TMV) and their family members by this new autonomic SS].
AB  - In Japan, many patients equipped with TMV are under medical treatment at home
      after 1990. These patients can't put out sputa in trachea, so that these
      patient's family members must suck these patient's intratracheal sputa all days.
      Mr Yamamoto and Mr Tokunaga, main researchers of this study, began the study on
      the automatic SS of itratracheal sputa from 1999. In first stage, They developed
      the intermittent SS in detaining the suction tube within tracheal cannula,
      monitering the intratracheal pressure, but this system takes the ventilation away
      from the patient. Hypoventilation caused by this SS may cause the serious
      accident in patient. Therefore, we remodel the SS from intermittent SS to
      rollerpomp-type SS continuing to suck the itratracheal sputa with low volume from
      2004, and thereafter we made up the SS of piston pomp type-SS finally at 2007. We
      developed the tracheal cannula with double suction holes of inner and lower hole
      in the lower part of its cannula together with the suction machine. We think that
      the practical use of this automatic SS will bring these patients with TMV and
      their family members great benefits. We desire that the practical use of this SS
      will be realized as soon as possible.

PMID- 20030237
TI  - [Development in researches for familial Parkinson's disease].

PMID- 20030238
TI  - [Pathogenesis of sporadic Parkinson's disease: contribution of genetic and
      environmental risk factors].
AB  - Parkinson's disease (PD) is the most common neurodegenerative disease after
      Alzheimer's disease. Although the pathogenetic mechanisms underlying PD is
      largely unknowm, it is widely believed that multiple genetic as well as
      environmental factors play critical roles in the development of PD. Alpha
      synuclein (a-SYN) and the disturbance of a-SYN metabolism seems to play the most
      important role in PD pathogenesis. a-SYN, the gene causative in PARK1, is the
      major component of Lewy bodies. Gene duplication or triplication of a-SYN leads
      to autosomal dominant form of familial PD, suggesting that disturbance of a-SYN
      may represent the etiology of sporadic PD. GBA and LRRK, the genes responsible
      for Gaucher disease and PARK8, respetively, are also likely to affect the
      development of PD. Studies of PD brains suggest that mitochondrial impairment and
      oxidative stress may contribute to the pathogenesis of sporadic PD. Mitochondrial
      complex I inhibitors, such as MPTP and rotenone, induce selective dopaminergic
      neuronal death, suggesting that chemicals may constitute risk factors of sporadic
      PD. Not only continuous infusion, but oral intake of rotenone is effective to
      establish animal models of PD. Further studies will reveal genetic or
      environmental risk factors, that are the good targets for prevention and therapy
      of PD.

PMID- 20030239
TI  - [Pathophysiological process underlying Parkinson's disease: motor & non-motor
      symptoms].
AB  - It is proposed that alpha-synucleinopathy initially affects the medulla oblongata
      and then progresses to more rostral brain areas ("Braak hypothesis"). According
      to this hypothesis, substantia nigra is affected in the later stages of PD.
      Another region affected in the earlier stages was reported to be olfactory bulb,
      although the following processes were not described in detail. On the other hand,
      several lines of evidence suggest that non-motor symptoms including constipation,
      depression, REM-sleep behavior disorder (RBD) and hyposmia may be prodromal
      symptoms in PD. The pathological staging postulated by the Braak hypothesis is in
      good agreement with the fact that these non-motor symptoms precede motor symptoms
      in PD, because affected brain areas in the early stages, such as dorsal vagal
      nucleus, locus ceruleus and olfactory bulb, are related to these non-motor
      features. Recently, it was reported that although half of brains corresponded to
      the Braak hypothesis, there were a high proportion of cases which did not fit the
      Braak's staging system and majority of the latter demonstrated amygdale
      predominant alpha-synucleinopathy. It was also demonstrated that the Lewy
      pathology in olfactory bulb was closely related to the presence of alpha
      synuclein pathology in amygdala. The amygdala is one of the main systems in odor
      perception and in PD, cortical neurons in corticomedial complex of amygdale,
      which have major olfactory connections, are selectively affected even in the
      early stages of the disease. We recently obtained the data suggesting that
      metabolic changes in the amygdala were associated with low scores in odor
      identification test. These data suggest that not only the olfactory bulb, but
      also the amygdala is also responsible for hyposmia in PD and that there may be
      another pathological process, which starts from the olfactory bulb and involves
      the amygdala.

PMID- 20030240
TI  - [Cell therapy for Parkinson disease].
AB  - Advances in the field of stem cell research have raised hopes of creating novel
      cell replacement therapies for Parkinson disease (PD), although double-blinded
      clinical trials have met with controversial success in patients implanted with
      fetal midbrain tissue and autopsy results have shown that some of the grafted
      fetal neurons displayed pathological changes typical of PD. Dopaminergic neurons
      have been efficiently derived from stem cells using various methods, and
      beneficial effects after transplantation have been demonstrated in animal models
      of PD. Some obstacles remain to be overcome before stem cell therapy can be
      routinely and safely used to treat PD in humans. A widely used prodrug/suicide
      gene therapy would be applied to stem cells to reduce risk of tumor formation.
      Since grafts were transplanted ectopically into the striatum instead of the
      substantia nigra in most current protocols, surviving dopaminergic neurons would
      not have to be the same subtype as the nigral cells. If the main mechanism
      underlying any functional recovery achieved by cell therapies is restoration of
      dopaminergic neurotransmission, then viral vector-mediated gene delivery of
      dopamine-synthesizing enzymes represents a more straightforward approach. Future
      targets for cell therapy should include some types of Parkinsonism with
      degeneration of striatal neurons.

PMID- 20030241
TI  - [Clinical overview of neuromyelitis optica].

PMID- 20030242
TI  - [Pathology of neuromyelitis optica].
AB  - Understanding of the pathogenesis of neuromyelitis optica (NMO) is rapidly
      growing. In our immunohistochemical studies from 2006, the loss of AQP4 was
      evident in about 90% of NMO lesions, especially in perivascular areas of acute
      inflammatory lesions where immunoglobulins and complements were deposited. Glial
      fibrillary acidic protein (GFAP) was also weak or lost in those lesions. In
      contrast, myelin basic protein (MBP)-stained myelinated fibers were relatively
      preserved in those lesions where AQP4 was completely lost. In contrast to NMO
      lesions, AQP4 and GFAP were preserved or increased in demyelinating MS lesions.
      The loss of AQP4 in acute inflammatory lesions was evident in the largest areas
      compared with GFAP or MBP, which probably suggested the primary loss of AQP4 on
      astrocytes and the secondarily demyelination. In contrast, the immunostaining
      patterns in more chronic lesions of NMO mostly lacked AQP4 but were necrotic
      heterogeneously with demyelination and gliosis, or completely burn-out. Swelling
      and regressive changes of astrocytes were easily evident. In addition, the
      lesions lacking AQP4 was appeared by passive-transferred Lewis rats with human
      purified IgG from NMO patients. Accordingly, these evidences strongly suggest its
      humoral autoimmune astrocytopathy in the pathomechanism of NMO.

PMID- 20030243
TI  - [Experimental models of neuromyelitis optica].
AB  - Recently a specific auto-antibody response has been found in patients with
      neuromyelitis optica, which is directed against the astrocytic water channel
      aquaporin 4. In experimental models these antibodies do not induce disease or
      lesions in the central nervous system, when present in the circulation of normal
      rats. However, when T-cell mediated inflammation is induced in such animals,
      circulating antibodies against aquaporin 4 can reach the brain and induce lesions
      in the central nervous system, which are closely similar to those, seen in
      patients with neuromyelitis optica.

PMID- 20030244
TI  - [Treatment of NMO].
AB  - The commonly used clinical diagnostic criteria for NMO still requires the
      presence of clinical episodes of both optic neuritis and myelitis. We believe
      this criteria has disadvantages for making early diagnosis in patients who fail
      to meet the criteria yet have the same disease process. Therefore we propose a
      simple new criteria which requires one of the following two: (1) centrally
      located, fully contiguous long spinal cord lesion (LCL) extending three or more
      spinal segments length or long segmental spinal cord atrophy and (2) presence of
      specific antibody to aquaporin-4 (AQP4). We also propose a new naming "autoimmune
      astrocytopathy" for such patients, since the autoimmune destructive process
      against astrocytes is the characteristic common underlying mechanism, the
      majority of patients show the clinical brain symptoms, and anti-AQP4 antibodies
      are frequently, but not exclusively, associated. The reanalysis of Japanese
      interferon beta-1b clinical trial data failed to show efficacy in patients
      meeting the diagnostic criteria for multiple sclerosis and showed MRI evidence of
      LCL. Although there is no evidence-based guideline for NMO, expert opinions
      generally agree with the treatment strategy. My treatment algorithm is shown in
      the table. At acute exacerbation, high-dose steroid infusion is the choice. If
      two cycles of infusion treatment fails to show recovery, plasma-exchange
      treatment should be initiated quickly. Medium dose oral steroids are started
      immediately after the end of high dose steroid infusion therapy. In moderate to
      severe activity cases additional usage of one of the immunosuppressants,
      Mizoribine, Tacrolimus, or Azathiopurine is quite useful, and the
      immunosuppressive effects on NMO are higher in this order, but the safety is
      higher at the opposite order. Therefore, selection of one of immunosuppressants
      should be made on individual basis and slow achievement of the immunosuppressive
      effects should be kept in mind especially in case of Azathiopurine. If any of
      these immunosuppressants are not successful in inducing stable state, then
      Mitoxantrone or Tituximab is the choice. The monthly infusion of former drug
      usually stablizes the disease activity quite quickly, but treatment duration is
      limited due to it's cardiotoxicity. Rituximab is also quite powerful in
      stabilizing the activity, but there still exist some non-or poor responder to
      this medicine, and insurance coverage is not expected for MS or NMO in Japan.
      Cyclophosphamide infusion is also an alternative choice for very difficult cases.
      Physicians working on NMO treatment in Japan are very much hoping the initiation
      of well controlled clinical trials in order to treat our patients with more
      scientific strategy based on evidences.

PMID- 20030245
TI  - [Molecular genetic approach to spinocerebellar ataxias].
AB  - Spinocerebellar ataxia (SCA) is a group of degenerative ataxias with autosomal
      dominant inheritance. The most common form of mutation that causes SCA is the
      expansion of trinucleotide (CAG) repeat encoding polyglutamine. These
      "polyglutamine disorders" are, SCA1, SCA2, Machado-Joseph disease, SCA6, SCA7,
      SCA17 and DRPLA. Another dynamic mutation, yet a non-coding one, has been
      identified as the cause of SCA8, SCA10 and SCA12. This mutation includes,
      trinucleotide (CAG/CTG) expansion causing SCA8 and SCA12, and pentanuclotide
      (ATTCT) expansion leading SCA10. In addition to these dynamic mutations, static
      mutations, such as missense mutations and deletions, have been identified to
      cause SCA5, SCA11, SCA13, SCA14, SCA15 and SCA27. Since 1992, authors have been
      involved in identifying the mutation (s) of autosomal dominant cerebellar ataxia
      with rather pure cerebellar syndrome (ADCAIII). About a half of our cohort with
      ADCAIII were SCA6, caused by a small CAG repeat expansion in the alpha1A-voltage
      dependent calcium channel gene. Recent study in patients' brains suggested that a
      small polyglutamine expansion leads a portion of this channel protein to
      aggregate in the Purkinje cell. Another type of ADCAIII is the chromosome 16q22.1
      linked ADCA. By a comprehensive positional cloning strategy, we have found a
      genetic change that segregate with the disease. Identifying the mutation of 16q
      ADCA is imperative for understanding molecular basis of this disease.

PMID- 20030246
TI  - [Genetic approach for understanding of the late-onset mechanisms of polyglutamine
      disease].
AB  - The intracellular accumulation of unfolded or misfolded proteins is believed to
      contribute to aging and age-related neurodegenerative diseases. However, the
      links between age-dependent proteotoxicity and cellular protein degradation
      systems remain poorly understood. Here, we show that 26S proteasome activity and
      abundance attenuate with age, which is associated with the impaired assembly of
      the 26S proteasome with the 19S regulatory particle (RP) and the 20S proteasome.
      In a genetic gain-of-function screen using Drosophila, we characterized Rpn11,
      which encodes a subunit of the 19S RP, as a suppressor of expanded polyglutamine
      induced progressive neurodegeneration. Rpn11 overexpression suppressed the age
      related reduction of the 26S proteasome activity, resulting in the extension of
      flies' life spans with suppression of the age-dependent accumulation of
      ubiquitinated proteins. On the other hand, the loss of function of Rpn11 caused
      an early onset of reduced 26S proteasome activity and a premature age-dependent
      accumulation of ubiquitinated proteins. It also caused a shorter life span and an
      enhanced neurodegenerative phenotype. Our results suggest that maintaining the
      26S proteasome with age could extend the life span and suppress the age-related
      progression of polyglutamine diseases.

PMID- 20030247
TI  - [Molecular therapy targeting protein misfolding and aggregation for the
      polyglutamine diseases].
AB  - Abnormal aggregation and deposition of misfolded proteins have been recognized as
      a common molecular pathogenesis of various neurodegenerative diseases including
      Alzheimer's, Parkinson's, and the polyglutamine (polyQ) diseases. The polyQ
      diseases, including Huntington's disease and various spinocerebellar ataxias, are
      caused by abnormal expansions of the polyQ stretch (> 35-40) within disease
      causative proteins, which are thought to trigger their misfolding and
      aggregation, leading to their deposition as inclusion bodies, and eventually
      resulting in neurodegeneration. We found that the expanded polyQ protein
      undergoes a conformational transition to a beta-sheet dominant structure in the
      monomeric state, triggering cytotoxicity, and subsequently resulting in formation
      of insoluble amyloid-like fibrillar aggregates. Targeting misfolding and
      aggregation of the expanded polyQ protein, we demonstrated that QBP1 (PolyQ
      Binding Peptide 1: SNWKWWPGIFD) prevents the toxic beta-sheet transition and
      aggregation of the expanded polyQ protein in vitro and suppresses polyQ-induced
      neurodegeneration in Drosophila. From high-throughput screening of a chemical
      compound library (46,000), we have identified approximately 100 polyQ aggregate
      inhibitors as therapeutic candidates so far. We also found that 17-AAG, an HSF1
      activating compound, suppresses polyQ-induced neurodegeneration in Drosophila
      through induction of endogenous molecular chaperones. We propose that our
      therapeutic strategy targeting protein misfolding and aggregation can also be
      applied to other neurodegenerative diseases.

PMID- 20030248
TI  - [Molecular-targeted therapies for spinal and bulbar muscular atrophy].
AB  - Spinal and bulbar muscular atrophy (SBMA) is a polyglutamine-mediated lower motor
      neuron disease characterized by slowly progressive muscle weakness and atrophy.
      The cause of this disease is the expansion of a trinucleotide CAG repeat, which
      encodes the polyglutamine tract, within the first exon of the androgen receptor
      (AR) gene. SBMA exclusively occurs in adult males, whereas both heterozygous and
      homozygous females are usually asymptomatic. Testosterone-dependent nuclear
      accumulation of the pathogenic AR protein has been considered to be a fundamental
      step of neurodegenerative process, which is followed by several molecular events
      such as transcriptional dysregulation, axonal transport disruption, and
      mitochondria dysfunction. Androgen deprivation suppresses the toxicity of the
      mutant AR in animal models of SBMA, and these insights have been translated to
      clinic. Animal studies have also suggested that activation of protein quality
      control systems are potential therapies for SBMA. To optimize "proof of concept",
      the process for testing candidate therapies in humans, it is of importance to
      identify responders to each therapy, to initiate interventions in early stages of
      the disease, and to establish biomarkers which can be used for evaluating the
      efficacy of treatment.

PMID- 20030249
TI  - [Molecular PET imaging for in vivo detection of amyloid in the human brain].
AB  - Neocortical deposition of amyloid plaques is one of the pathological hallmarks of
      Alzheimer's disease (AD). In vivo detection of amyloid plaques in the brain
      enables early identification of AD patients. Many beta-sheet binding agents have
      been developed as amyloid-binding radiotracers for PET. Currently, the most
      successful amyloid-binding agent is 11C-PIB. PET amyloid-imaging studies in human
      subjects have shown a robust difference between the retention pattern in AD
      patients and healthy controls. In vivo amyloid-imaging enables early and accurate
      detection of AD patients in the stage of MCI. The demonstration of abnormal
      tracer retention in a proportion of the elderly normal subjects supports post
      mortem observations that the amyloid deposition predominantly occurs before the
      onset of dementia. For presymptomatic diagnosis of AD, longitudinal studies are
      needed to elucidate the relation between amyloid deposition and time course of
      AD. AD and many other neurodegenerative disorders belong to the family of protein
      misfolding diseases, characterized by protein self-aggregation and deposition.
      Molecular PET imaging using beta-sheet binding agents has the potential to be
      extended to these wide spectrums of protein misfolding diseases.

PMID- 20030250
TI  - [Imaging of brain microgliosis by PET].
AB  - Microglia in the brain are no longer quiescent but active by extending their
      dendrite and villi to their vicinity, so that microglia play roles in immune
      surveillance in a similar way as macrophages in the periphery. Changing their
      shapes from ramified to ameboid forms is a sign of neuroinflammation triggered by
      damaged neurons or astrocytes. This microgliosis is caused not only by direct
      brain injury or vascular damage but neurodegeneration, the latter of which was
      first shown in Alzheimer's disease in vivo by PET with widely-used peripheral
      benzodiazepine receptor (PBR) tracer [11C] (R)-PK11195. The number of the PRB is
      reportedly increased on the surface of mitochondrial adventitia of the activated
      microglia, but the affinity to the tracer is shown stable. Using this tracer is
      advantageous to depict the level of neuroinflammation in vivo in many
      neurodegenerative diseases. However, the weak point of the tracer is no capacity
      to differentiate protective microglia from proinflammatory ones. So, a new tracer
      with its segregation capacity would be expected to come in the near future. This
      talk is going to cover the application of the PBR tracer to image the
      neuroinflammation in vivo in neurological and psychiatric diseases.

PMID- 20030251
TI  - [In-vivo imaging for pursuing molecular cascades in the pathogenesis of
      neurodegenerative diseases].
AB  - Nonclinical and clinical evidences have supported the view that accumulations of
      neurotoxic amyloid components initiate chain reactions of molecular and cellular
      pathologies, eventually leading to neuronal death and symptomatic onsets of
      neurodegenerative diseases. As this amyloid-triggered cascade is virtually
      composed of bidirectional causalities between upstream and downstream events, it
      is of critical significance to monitor all key processes, including amyloidosis,
      neuroinflammation, disrupted calcium homeostasis and impaired neurotransmissions,
      in living brains toward therapeutic regulations of the entire cascade. Positron
      emission tomography (PET) offers quantitative mapping of these alterations with
      the aid of multiple classes of radioprobes. Comparative PET assays of humans and
      animal models in conjunction with cognitive, biochemical and histopathological
      assessments have revealed toxic subspecies of amyloid beta peptide, tau proteins
      and microglia detectable by specific molecular probes. Dysregulated
      neurotransmissions are also capturable by PET techniques, while it should be
      noted that the accessibility of binding components to exogenous radioligands does
      not simply reflect their amounts but also is affected by their translocation,
      posttranslational modifications and interaction with endogenous ligands and other
      molecules. Clarification of these changes in target elements brings mechanistic
      insights into the molecular etiology of neuropsychiatric disorders.

PMID- 20030252
TI  - [Neuroimaging studies on higher brain functions].
AB  - For the research on human higher brain functions, both neuropsychological and
      neuroimaging studies are useful, but each of these two methodologies has merits
      and demerits. In neuropsychological studies, damaged regions are necessary for
      the normal execution of cognitive functions underlying the symptoms that patients
      show. However, it is usually difficult to determine to what extent the lesion has
      affected a specific psychological subprocess amongst several subprocesses related
      to the symptoms. On the other hand, in neuroimaging studies, activated regions
      may not be necessary for but simply participate in a targeted higher brain
      function. However, if we can set up an adequate experimental design, it provides
      an opportunity to identify brain regions related to a specific psychological
      subprocess necessary for the targeted higher brain function. In this symposium, I
      talked about several neuroimaging studies using positron emission tomography and
      functional magnetic resonance imaging. We can take advantage of neuroimaging
      techniques for the research on human brain functions, but it should be kept in
      mind that neuroimaging techniques are not the purpose of the research but simply
      one of the useful means.

PMID- 20030253
TI  - [History of 50 years of prion disease research].
AB  - The history of the research of the prion disease is consolidated in 50 years
      after the Japanese neurology association starts. It was proven that it was an
      infectious disease from kuru that was a local disease of New Guinea, explained
      how CJD, the scariest disease for a neurologist, had come to be called a prion
      disease, and even a newly emerging prion disease referred in the future.

PMID- 20030254
TI  - [Prion disease surveillance in Japan: analysis of 1,241 patients].
AB  - The Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1,241
      patients with prion diseases during 1999-2009, including 953 with sporadic CJD
      (sCJD) (76.8%), 207 with genetic prion diseases (16.7%), 78 with environmentally
      acquired prion diseases (6.3%), and 3 with unclassified CJD. Among atypical cases
      of sCJD, most common was MM2 type including the cortical and thalamic forms. The
      genetic cases included 84 with a PrP V180I mutation (40.6%), 37 with a P102L
      mutation (17.9%), 34 with a E200K mutation (16.4%), 32 with a M232R mutation
      (15.5%), 4 with a P105L mutation (1.9%), and so on. The environmentally acquired
      cases included 77 with dura mater graft-associated CJD (dCJD) and one with
      variant CJD (vCJD). Combined with the results by the previous surveillance
      systems, a total number of dCJD in Japan was 135. The vCJD patient had a history
      of short stay in the UK and presented with periodic electroencephalogram in the
      late stage. Although there was no evidence of association of surgical procedures
      or blood transfusion with sCJD, 4.5% of the sCJD patients underwent operations
      after the onset of sCJD, including neurosurgical for 0.8% and ophthalmic for
      1.9%, requiring more attention on prion diseases to reduce the iatrogenic risk.

PMID- 20030255
TI  - [Clinical features and PRNP abnormalities of prion diseases].

PMID- 20030256
TI  - [Innovation of therapeutics and prophylaxis for prion diseases].
AB  - There is no established treatment for prion diseases; however, recently several
      drug candidates, including pentosan polysulfate and doxycycline, have been
      clinically used on a trial basis to prevent accumulation of abnormal prion
      protein in the brain. So far the outcome of the trials is still very far from the
      goal where a complete cure of the diseases is expected. In order to bridge the
      gap between the reality and the ideal, the followings are suggested. First,
      combination therapy needs to be developed against multi-targets: inhibition of
      prion replication; degradation and scavengery of prion; inhibition of prion
      related neurodegeneration. Secondly, preclinical diagnostic means, by which
      healthy prion-carriers can be revealed before the onset of the diseases, should
      be explored for earlier therapeutic interventions. The last is to disclose
      intrinsic disease susceptibility factors and environmental factors, both of which
      could solely or jointly facilitate in suppressing prion replication and disease
      progress. Exploitation of these items should be tough but will be deserved for
      overcoming the fatal diseases.

PMID- 20030257
TI  - [Wide spectrum of hereditary motor sensory neuropathy (HMSN)].
AB  - Hereditary neuropathies are classified into HMSN/Charcot-Marie-Tooth disease
      (CMT), familial amyloid polyneuropathy (FAP), hereditary motor neuropathies (HMN)
      and hereditary sensory (and autonomic) neuropathies (HSAN). The clinical features
      of HMSN are generally characterized as distal dominant motor and sensory
      involvements. However, we have reported a novel HMSN with proximal dominancy
      (HMSN-P) originated in Okinawa and Shiga prefectures, Japan. The gene locus is
      located in the centromere region of chromosome 3. In 2008, a new family with the
      HMSN-P was reported from Brazilians of Japanese ancestry. This Brazilian family
      was initially diagnosed as having "a familial ALS". The HMSN-P linked to ch.3 is
      not limited in Japan, but may be present in the worldwide. The overseas
      scientific research for the elucidation of the mechanism of HMSN-P supported by
      JSPS KAKENHI (21406026) is planning. Recently several other types of HMSN-P have
      been reported; HMSN-P with urinary disturbance and paroxysmal dry cough, a
      patient with both CMT 1A and mild spinal muscular atrophy and CMT1A with severe
      paresis of the proximal lower limb muscles. Therefore the clinical concept of
      HMSN is not limited as the disease with distal dominant motor sensory
      involvement. HMSN has the wider spectrum from distal to proximal and
      motor/sensory to autonomic neuropathies.

PMID- 20030258
TI  - [Therapeutic strategy for familial amyloid polyneuropathy (FAP)].
AB  - Familial amyloid polyneuropathy (FAP) was long considered to be an incurable
      disease, but a new therapeutic approach was developed 15 years ago. As the liver
      produces most of the transthyretin (TTR) in serum, it was assumed that the
      replacement of a liver expressing an abnormal TTR gene should stop the production
      of the variant TTR, the serum amyloid precursor in FAP. Until now about 1,500 FAP
      patients underwent liver transplantation, and the 10-year-survival rate is about
      77%. After operation the progression of FAP symptoms certainly stopped, and
      patients who were in an early stage of the disease and underwent successful
      operations showed considerable improvement in their quality of life.
      Electrophysiological study of peripheral nerve function has demonstrated that
      liver transplantation can halt the progression of peripheral neuropathy in FAP
      patients, and histopathological regression of amyloid deposits was seen on the
      patients with long post-transplatation courses. Pharmacological therapies have
      been considered for FAP patients and among them, diflunisal, one of non-steroidal
      antiinflammatory drugs, is very promising. TTR tetramer dissociation is an
      initial step for the process of TTR-derived amyloid fibril formation associated
      with FAP and diflinisal can inhibit this process by stabilization of the TTR
      tetramer. Clinical trial of this drug for FAP patients is now going worldwide.

PMID- 20030259
TI  - [Immune-mediated neuropathies].
AB  - Such neuropathies as Guillain-Barre syndrome (GBS), chronic inflammatory
      demyelinating polyneuropathy (CIDP), and IgM paraproteinemic neuropathy are
      caused by autoimmune mechanisms. IgM paraproteinemic neuropathies are known to be
      intractable. Rituximab has recently been reported to be effective for IgM
      paraproteinemic neuropathy with anti-MAG IgM M-protein in a placebo-controlled
      trial. The effect should be confirmed with a larger trial. The use of this drug
      also may be tried for other type of IgM paraproteinemic neuropathy and for
      intractable CIDP in future. Antiganglioside IgG antibodies are frequently present
      in the acute-phase sera from GBS patients. Recently, presence of the antibodies
      that recognize a conformational epitope formed by carbohydrate portions of two
      different gangliosides (ganglioside complex) has been reported. Antibodies
      against a complex formed by GD1a and GD1b (anti-GD1a/GD1b antibodies) are
      associated with severe GBS. Anti-GM1/GalNAc-GD1a antibodies are found to be
      associated with pure motor GBS with frequent conduction block. Anti-ganglioside
      complex antibodies may be useful diagnostic and prognostic markers of GBS. Future
      study is necessary to clarify the pathogenetic mechanisms in which those
      antibodies are specifically involved.

PMID- 20030260
TI  - [Peripheral neuropathy and blood-nerve barrier].
AB  - It is important to know the cellular properties of endoneurial microvascular
      endothelial cells (PnMECs) and microvascular pericytes which constitute blood
      nerve barrier (BNB), since this barrier structure in the peripheral nervous
      system (PNS) may play pivotal pathophysiological roles in various disorders of
      the PNS including inflammatory neuropathies (i.e. Guillain-Barre syndrome),
      vasculitic neuropathies, hereditary neuropathies and diabetic neuropathy.
      However, in contrast to blood-brain barrier (BBB), very few studies have been
      directed to BNB and no adequate cell lines originating from BNB had been
      launched. In our laboratory, we successfully established human immortalized cell
      lines originating from BNB using temperature-sensitive SV40 large T antigen and
      the cellular properties of human cell lines are presented in this paper. Human
      PnMEC cell line showed high transendothelial electrical resistance and expressed
      tight junction components and various types of influx as well as efflux
      transporters that have been reported to function at BBB. Human pericyte cell line
      also possessed tight junction proteins except claudin-5 and secrete various
      cytokines and growth factors including bFGF, VEGF, GDNF, NGF, BDNF and
      angiopoietin-1. Co-culture with pericytes or pericyte-conditioned media
      strengthend barrier properties of PnMEC, suggesting that in the PNS, peripheral
      nerve pericytes support the BNB function and play the same role of astrocytes in
      the BBB. Future accumulation of the knowledge concerning the cellular properties
      of BNB-forming cells will open the door to novel therapeutic strategies for
      intractable peripheral neuropathies.

PMID- 20030261
TI  - [Neurology education and the history of the Korean Neurological Association].

PMID- 20030262
TI  - [Neurology education and history of Taiwan Neurological Society].

PMID- 20030263
TI  - [History of neurology and education on neurology in Japan].
AB  - The first medical society of Japanese neurologists and psychiatrists was founded
      in 1902, but psychiatrists gradually dominated in number. New "Japanese Society
      of Neurology" (JSN) was founded in 1960. The number of members was only 643 in
      1960, while it rose up to 8,555 in 2009, including regular, junior, senior and
      associate members. JSN contributed much to solve the causes and treatment of the
      medicosocial and iatrogenic diseases such as Minamata disease and SMON (subacute
      myelopticoneuropathy) at its early period. In undergraduate education at medical
      school neurology is one of the core subjects in the curriculum, and almost all
      the 80 medical schools have at least one faculty neurologist. The Board of
      neurology of JSN was started in 1975, as the third earliest of the Japanese
      Medical Associations. It takes at least 6 years' clinical training after
      graduating from the medical school to take the neurology Board examinations. By
      2009, 4,000 members passed the Board examinations. In 2002 JSN published evidence
      based "Treatment Guidelines 2002" of 6 diseases: Parkinson's disease, stroke,
      chronic headache, dementia and ALS. As to the international issues, JSN hosted
      the 12th World Congress of Neurology in 1981, and international activities
      markedly increased after that. The first informal meeting with JSN and Korean
      Neurological Association (KNA) was held at the 48th JSN Annual Meeting in Nagoya
      in May 2007. In May 2008 the KNA-JSN 1st Joint symposium was held at the 49th
      Annual Meeting of JSN in Yokohama on "International comparison of neurological
      disorders: focusing on spinocerebellar atrophies (SCA) and epilepsies". In May
      2009, KNA-JNS 2 nd Joint Symposium was held at the 50th JSN Annual Meeting in
      Sendai, inviting a speaker from Taiwan Neurological Society, on the subject
      "History and Education of Neurology in Japan, Korea and Taiwan". In this
      symposium, a strategy to make up the Northeast Asian Neurological Association was
      discussed.

PMID- 20030264
TI  - [Lipid peroxidation in pneumonia of bacterial and viral etiologies].
AB  - The blood prooxidant and antioxidant systems were studied in 165 patients with
      pneumonia of bacterial and viral etiologies over time. There was a regular and
      significant increase in the levels of malondialdehyde, spontaneous nitroblue
      tetrasolium test, and catalase in the red blood cells; in parallel to this, there
      was ceruloplasmin activity suppression that depended on etiology, stage, and
      severity. Much pronounced and long-term impairments of the activity and level of
      prooxidant and antioxidant indices were suggestive of a severer clinical course
      and the presence of complications and concomitant diseases of infectious and
      inflammatory nature.

PMID- 20030265
TI  - [Prescreening of the activity of alanine aminotransferase enhances the cost
      effectiveness of blood storage].
AB  - The cost-effectiveness of prescreening for alanine aminotransferase (ALT)
      activity was evaluated in blood donors before donation. Since September 15, 2006,
      the Krasnodar Territory blood transfusion station has examined more than 32
      thousand donors in this fashion. A Reflotron Plus biochemical analyzer (Roche
      Diagnostics, Switzerland) was used. In 2008, 1230 subjects with increased ALT
      activity were withdrawn from donation. A total of 17,096 persons were examined.
      Their examination cost 1,219,457.8 rubles. Non-productive outlays of 7,773,919.8
      rubles were prevented. The savings amounted to 6,554,462.12 rubles. Prescreening
      for ALT was found to be cost-effective if the rate of positive results in the
      donor population was 1.13% or more.

PMID- 20030266
TI  - [The serum content of gastrin-17 and pepsinogen-1 in patients with duodenal
      ulcerative disease in occupational contact with nitrogenous compounds].
AB  - The levels of serum gastrin-17 (G-17) and pepsinogen-1 (P-1) were studied in 54
      patients with duodenal ulcerative disease (UD) who worked at chemical plants
      manufacturing nitrogenous compounds and in 15 healthy individuals (a control
      group). There are objective data on the time course of changes in the functional
      characteristics (G-17 and P-1) of the gastric mucosa (GM) in the patients with
      duodenal UD, which vary with the chemical compositions of hazardous substances
      and the length of service at a chemical plant. Basic therapy for UD causes
      positive changes in the functional parameters reflecting the state of GM.

PMID- 20030267
TI  - [Clinical and laboratory indicators of systemic inflammation and endotoxicosis in
      the evaluation of the activity of an infectious process].
AB  - Patients with chronic brucellosis underwent a complex clinical and laboratory
      studies to determine the indicators reflecting the degree of systemic
      inflammation and endotoxicosis. On the basis of an analysis of the findings, an
      integral quantitative approach was applied to describing the associations between
      various pathophysiological processes and clinical manifestations; criteria for
      the activity of the infectious process were objectivized, and the form of chronic
      brucellosis was defined. The mathematical simulation method was shown to be an
      adequate tool to objectivized the differential diagnosis of the clinical forms of
      the disease.

PMID- 20030268
TI  - [Comparison of the state of the gastrointestinal tract with the values of lipids
      and their peroxidation in patients with atheromatosis of the celiac trunk].
AB  - The values of lipidemia were studied, by comparing with the levels of lipid
      peroxidation products and the state of antioxidant defense in patients with
      atheromatosis of the celiac trunk. A group of patients with ischemic
      enterocolonopathies showed a trend for the level of low-density lipoprotein
      cholesterol to increase as compared with abnormalities at other sites. In
      patients with ischemic gastropathies, the levels of heptane-soluble ketodienes
      and conjugated trienes were higher than those in patients with pancreatopathies
      and enterocolonopathies.

PMID- 20030269
TI  - [AB0 blood group-associated biological variability in the content of
      metabolites].
AB  - The performed studies provided new evidence for biological variability in
      clinically important analytes, estimated a possible association of the metabolic
      features and the conservative genetic attribute--the ABO blood group. Certain
      features in the levels of protein, carbohydrate, lipid, and mineral metabolic
      parameters were revealed in relation to various blood groups.

PMID- 20030270
TI  - [Statistical control of the quality of clinical laboratory analyses (a lecture)].
AB  - No measurement can be absolutely precise, but, by using the methods of the
      probability theory and by knowing the nature of errors, one can estimate a
      probable size. The paper considers the specific features of measurements during
      clinical laboratory analyses, as well as those of statistical methods for
      assessing their validity. The first part contains general provisions; the second
      one outlines numerical methods for assessing the quality of performed work. The
      procedures using both the data of analyses carried out in patients and those of
      special studies of a control biological material of known and unknown
      composition. Most numerical methods suggest that a laboratory has at its disposal
      a computer connected to an analyzer, but a few, quietly reliable assessments can
      be also manually made. The paper gives only final conclusions and recommendations
      and omits rather intricate mathematical proofs, which are for information
      available at the web site clilab.ru in the section "Introduction to statistical
      quality control".

PMID- 20030271
TI  - [Examining the relationship between the electrophoretic mobility of peripheral
      red blood cells and their sedimentation rate in patients with hemophilia].
AB  - The correlation between the erythrocyte sedimentation rate (ESR) and the
      electrophoretic mobility (EPM) of red blood cells in patients with hemophilia was
      studied due to the data available in the literature, showing an inverse relation.
      Anticoagulant-stabilized venous blood was a material to be tested. Patients with
      severe hemophilia A or B (factor VIII/IX < 1%; the normal values were 50-200%)
      were examined. The patients were divided into 2 groups: 1) those with an
      exacerbation of hemorrhagic syndrome and 2) those without an exacerbation. The
      patients with hemophilia with an exacerbation of the hemorrhagic syndrome showed
      a certain correlation between ESR and EPM, yielding two type of curves, which
      corresponded to two subgroups of patients. There was no correlation between EPM
      and ESR in the no-exacerbation group.

PMID- 20030272
TI  - [Use of molecular genetic diagnostic methods in periodontology and implantology].
AB  - The authors have studied the species-specific composition of major
      periodontopathogenic bacteria (P. gingivalis, P. intermedia, B. forsythus, A.
      actinomycetemcomitans, and T. denticola), by applying the Russian reagent kit
      developed and made by HPF "GENETECH", and some fungi, microorganisms, and viruses
      among the Moscow Region inhabitants with chronic generalized periodontitis in
      2006-2008. The studies have shown it possible to use molecular genetic methods
      for diagnosis, drug therapy monitoring, and epidemiological studies in
      periodontology and implantology.

PMID- 20030273
TI  - [Laboratory diagnosis of cholera: analysis and prospects for improvement].
AB  - Microbiological monitoring of the circulation of Vibro cholerae remains one of
      the key factors contributing to optimization of epidemiological surveillance in a
      specific area and the laboratory diagnosis of cholera is a basic applied tool for
      the detection and characterization of isolated cultures. The quality of
      etiological identification of the pathogen, the competent use of procedures, and
      the observance of a laboratory diagnosis scheme increases the likelihood of the
      cholera pathogen being detected in the samples taken from human beings and
      environmental objects, which allows to timely notify the disease and to prevent
      it. The current goals of investigations include the development of more
      accessible and rapid methods that would further find their place in the scheme
      for the laboratory diagnosis of cholera.

PMID- 20030274
TI  - [Human caliciviruses and an immune response].
AB  - The review deals with calicivirus infection that has long been known in animals,
      but also just recently disclosed in humans. Human caliciviruses induce outbreaks
      of acute gastroenteritis in all countries of the world, which makes this
      immunobiological research very actual. The history of this discovery, evolution
      of caliciviruses, the host resistance and immune response mechanisms are
      described in this review.

PMID- 20030275
TI  - [Impact of asymptomatic herpesvirus infection on the female reproductive system].
AB  - The fact that asymptomatic and subclinical isolation of the virus in the
      Infected, which is, according to the data of different authors, noted in 50-90%
      of cases, presents the highest hazard to the spread of herpesvirus infection may
      be now considered to be proven. The development of assisted reproductive
      technologies have led to the active study of the factor of male infertility in
      marriage, including that of the negative impact of asymptomatic infection caused
      by herpes simplex virus (HSV) on spermatogenesis. At the same time, there is no
      consent of opinion as to the implication of asymptomatic HSV in female
      reproductive dysfunction. The presented review attempts to analyze the data
      available in the literature on the detection of HSV in the reproductive organs of
      a woman without a history of the clinical episodes of the disease and to assess a
      role of HSV infection in the development of female infertility.

PMID- 20030276
TI  - [Herd immunity against poliomyelitis in children in the Moscow Region].
AB  - Herd immunity against poliomyelitis was studied in 1391 children and adolescents
      from 10 towns of the Moscow Region. It was ascertained that the values of herd
      immunity against poliomyelitis virus type 1 were high everywhere and those of
      herd immunity against poliomyelitis virus type 2 were high and very high in 9
      towns and below the WHO minimum levels (80%). The values of herd immunity against
      poliomyelitis virus type 3; they were lower than the required minimum in 2 towns
      and very low in 2 other towns arouse alarm. The study of strain-specific
      antibodies to vaccine-derived and wild polioviruses has demonstrated that wild
      poliomyelitis viruses have not circulated in the areas of the examinees in the
      past decade.

PMID- 20030277
TI  - [Herpesvirus type 8 and its implication in human pathology].
AB  - Herpesvirus type 8 or Kaposi's sarcoma-associated virus has been recently
      discovered and it is an etiologic agent of several known diseases. It has common
      features that link it with other representatives of the family Herpesviridae:
      similar structural elements and genomic organization, and the common mechanisms
      of replication. Nevertheless, this virus has a number of unique features that
      make it an interesting matter for investigations and currently central in modern
      medicine and biology. This overview is to draw attention to this representative
      of herpesviruses and to outline some epidemiological, pathogenetic, and molecular
      aspects of this problem.

PMID- 20030278
TI  - [Genetic diversity of human caliciviruses detected in schoolchildren with
      gastroenteritis in Nizhni Novgorod].
AB  - A total of 2312 children admitted to the Nizhni Novgorod infectious disease
      hospitals for diagnosed acute gastroenteritis were examined using the RT-PCR. The
      detection rate of human caliciviruses was found to be 6.5% (range 1.2 to 11.2%).
      The population of calicivuruses presented with noroviruses genogroups I (16%) and
      II (81%), and sapoviruses (3%). Noroviruses genogroup II included genotypes GII.2
      and GII.4 with a preponderance of the variant CII.4-2006b. The detected
      sapoviruses were clustered with sapoviruses GI.1, GI.2, and GII.1 by phylogenetic
      analysis.

PMID- 20030279
TI  - [Identification of human pathogenic variola and monkeypox viruses by real-time
      polymerase chain reaction].
AB  - A kit of specific oligonucleotide primers and hybridization probes has been
      proposed to detect orthopoxviruses (OPV) and to discriminate human pathogenic
      viruses, such as variola virus and monkey virus by real-time polymerase chain
      reaction (PCR). For real-time PCR, the following pairs of fluorophore and a
      fluorescence quencher were used: TAMRA-BHQ2 for genus-specific probes and FAM
      BHQ1 for species-specific ones (variola virus, monkeypox virus, ectomelia virus).
      The specificity of this assay was tested on 38 strains of 6 OPV species and it
      was 100%.

PMID- 20030280
TI  - [Localization of human cytomegalovirus immediate-early protein IE-1 pp72 in the
      juxtanuclear inclusion at the late stage of infection].
AB  - Immediate-early protein IE-1 pp72 is one of the most abundant proteins at the
      early stage of human cytomegalovirus infection and has a number of intranuclear
      activities. This paper gives immunocytochemical and ultrastructural data on IE-1
      pp72 accumulation in the juxtanuclear inclusion at the late stage of low
      multiplicity infection. Detection of a new localization site infers that this
      protein may participate in the final steps of virus morphogenesis and play a
      functional role in the pathogenesis of cytomegalovirus infection.

PMID- 20030281
TI  - [Chemotherapy for Bolivian hemorrhagic fever in experimentally infected guinea
      pigs].
AB  - The efficacy of the antiviral agents nucleoside analogues manufactured in Russia
      and foreign countries against Bolivian hemorrhagic fever in the treatment and
      rapid prevention regimens was studied in guinea pigs. In rapid prevention and
      treatment of guinea pigs, the intraperitoneal injection of 1/10 of the equivalent
      dose of vero-ribavirin for this animal species was ascertained to protect 70% of
      the animals infected with Machupo virus strain Carvallo in doses 8 and 10 LD50.

PMID- 20030282
TI  - [Nevirapine as an important component of therapy for HIV infection].

PMID- 20030283
TI  - [The innovator of Russian virology (on the occasion of the 100th anniversary of
      Academician M.P. Chumakov's birth)].

PMID- 20030284
TI  - [Live oral poliomyelitis vaccine is 50 years old].

PMID- 20030285
TI  - [True body water volume in patients on peritoneal dialysis].
AB  - Body water volume (BWV) equals urea distribution volume (UDV), crucial for
      accurate calculation of dialysis dosage from urea clearance in patients treated
      with peritoneal dialysis. BWV is precisely determined only by monitoring tritium-
      or deuterium--labeled water concentration in patient plasma. These are not
      routine methods, thus a number of alternative methods and anthropometric formulas
      have been used instead trying to determine BWV from patient body weight and body
      height, age and sex. These methods are relatively simple but not fully reliable.
      In the present study, BWV being mostly determined by use of Watson formula at the
      time of peritoneal dialysis and upon switching to hemodialysis or undergoing
      kidney transplantation, was monitored in peritoneal dialysis patients to
      demonstrate that it significantly exceeded the value obtained by the formula.
      Immediately before switching to hemodialysis or undergoing kidney
      transplantation, 39 patients (14 female, 25 male) without dialysate in the
      abdomen had a mean body weight of 74.60 +/- 12 kg and mean BWV of 37.90 +/- 5.80
      L according to Watson formula. In the first month of switching to another
      dialysis method, all patients reduced their body weight by a mean of 3.35 +/-
      2.55 kg. Now, their mean body weight was 71.25 +/- 11.45 kg and mean BWV 36.80 +/
      5.50 L. However, differences in the mean body weight and BWV did not reach
      statistical significance (t body weight = 1.25; t body water = 0.84; p>0.05). The
      body weight reduction during the period of observation could have almost
      certainly been ascribed to the accumulated fluid elimination. This in turn
      implies that immediately before switching to hemodialysis or undergoing kidney
      transplantation, peritoneal dialysis patients had a total body water greater by a
      mean of 3.35 +/- 2.55 L than the figure obtained by Watson formula. Thus, their
      BWV was not 37.90 +/- 5.80 L (50.80 +/- 7.75% of body weight) but 41.25 +/- 6.85
      L (55.16 +/- 9.15% of body weight). According to t-test, then their true BWV
      statistically significantly (by 8.83%) exceeded the figure yielded by the formula
      (t=2.39; p<0.05), the Kt/V was falsely higher by approximately the same
      percentage, and the BWV reduction upon switching from peritoneal dialysis to
      another dialysis method or undergoing kidney transplantation was statistically
      significant (41.25 +/- 6.85 vs. 36.80 +/- 5.50 L; t=3.20; p<0.01). In conclusion,
      retrograde assessment of BWV in patients treated by peritoneal dialysis showed
      the BWV calculated by the most widely used anthropometric formula to be
      considerably underestimated and urea clearance overestimated for the same reason.

PMID- 20030286
TI  - [Operative deliveries in Clinic of Gynecology and Obstetrics Tuzla, Bosnia and
      Herzegovina, during 1986-2005].
AB  - The aim of this paper was to determine the incidence of operative deliveries and
      to make a comparison between the incidence rate in the pre-war (1986-1991), war
      (1992-1995) and post-war (1996-2005) periods. METHODS: We retrospectively
      collected data from the databases of University Clinic of Gynecology and
      Obstetrics Tuzla for the period of twenty years (January 1st, 1986 - December
      31st, 2005). RESULTS: The frequency of Cesarian section was in constant rise
      since 1990 when it surpassed 11%, with the exception of two war years 1992 and
      1993 when it was 9.5%. The highest frequency was registered in 2004 - 20.7%.
      Statistically significant difference in Cesarean section was found between period
      2001-2005 (18.5%) and other analysed periods. Vacuum extraction methods were most
      used in 1989 - 3.7%, and least in 2004 - 1.1%. In 1991, 50 - 0.8% of deliveries
      were finished with forceps, and since 2000 this method has not been used in any
      delivery. The frequency of pelvic presentation for the analyzed period varied
      less and was between 2.9% and 5.1%. CONCLUSION: During the period of twenty years
      at the Clinic of Gynecology and Obstetrics in Tuzla a significant increase in the
      incidence of deliveries finished with Cesarean section was found.

PMID- 20030287
TI  - [Ultrasound-guided thrombin injection for the treatment of femoral artery
      pseudoaneurysms--report of three cases].
AB  - Authors report three cases of patients with iatrogenic, postcatheterization
      femoral artery pseudoaneurysms successfully treated with percutaneous ultrasound
      guided thrombin injection (UGTI). The technique of UGTI is described, as well as
      advantages and complications of this method. These cases highlight the role of
      UGTI in the management of the postcatheterization pseudoaneurysms.

PMID- 20030288
TI  - [Cholesterol crystal embolism and renal insufficiency: case report and literature
      review].
AB  - Cholesterol crystal embolism with renal impairment is increasingly recognised as
      an iatrogenic complication of invasive vascular procedures. We present a 58-year
      old patient in whom the presence of a classic triad of precipitating event
      (coronary angiography), subacute presentation of renal failure and cutaneous
      lesions (livedo reticularis and Blue Toe syndrome) suggested this entity. The
      confirmatory diagnosis was made by means of renal biopsy which revealed
      cholesterol crystals lodged in arteries. In our patient severe renal
      insufficiency requiering hemodialysis ensued. Glucocorticoid and statin therapy
      failed to recover the renal function. The patient died from acute myocardial
      infarction. Invasive cardiac procedures are increasing in number especially in
      the elderly population so higher incidence of cholesterol crystal embolism coud
      be expected in the future. Increased awareness of this syndrome is necessary for
      early recognition, which is crucial for treatment, and defining the high-risk
      patient in whom other modalities of coronary diagnostics coud be considered.

PMID- 20030289
TI  - [Narrow band imaging: new paradigm in gastrointestinal video-endoscopy].
AB  - Novel technologies in gastrointestinal endoscopy, such as magnification and high
      resolution endoscopy, have a clear aim in improving diagnostic accuracy of
      mucosal abnormalities. Narrow band imaging encompasses both of these by
      endoscopic display of gastric mucosa with bands of blue and green light. This
      enhances mucosal architecture and adjacent vasculature. Combined with optical
      magnification NBI enables recognition of subtle mucosal abnormalities, such as
      dysplasia in Barrett's oesophagus, early morphological changes of vasculature in
      inflammatory and malignant diseases of esophagus, stomach and colon. Before NBI
      becomes a routine diagnostic procedure, further investigations are needed
      especially in regard to standardisation and validation of findings, as well as
      their correlation with histopathological findings.

PMID- 20030290
TI  - [Microbiological diagnosis of trichinellosis].
AB  - Trichinellosis is a parasitic mammalian disease caused by roundworms from the
      Trichinella genus. It is an important zoonosis with humans becoming infected by
      eating raw or inadequately cooked infested meat. The disease is widespread and
      represents a public health problem. According to the World Health Organisation
      estimations, some 11 million people are infected by Trichinella annually.
      Trichinellosis has a broad clinical presentation, ranging from asymptomatic to
      fatal. Since there are no pathognomonic signs or symptoms, clinical diagnosis is
      difficult and the only reliable diagnostic methods are those parasitological.

PMID- 20030291
TI  - [Diagnostic-therapeutic guidelines for men whose partners have HPV genital
      infection].
AB  - Human papilloma virus infection is the most frequent sexually transmitted
      disease. HPV infections are connected with different diseases such as benign
      warts, condylomata acuminata, malignant cervical, vulvar, vaginal, penile and
      anal carcinoma. Peniscopy with HPV detection is a specific diagnostic method for
      diagnosis of subclinical HPV genital infection in asymptomatic men. Taking the
      samples for HPV detection from asymptomatic men with curette is more qualitative
      way of getting enough samples then taking swab with wooden stick or (tongue)
      depressor. Early diagnosis and treatment of HPV infections in men is of potential
      benefit because their eradication can reduce the viral reservoir and as the
      result of that the incidence of CIN, carcinoma in situ and invasive cervical
      carcinoma can be reduced. For the correct diagnosis and for choosing the adequate
      therapeutical technique, we suggest diagnostic-therapeutic guidelines for HPV
      genital infection in men.

PMID- 20030292
TI  - [Dysmenorrhea induced by lumbosacral spine disorders. Pathogenesis, diagnosis and
      therapy with special emphasis on spinal manipulative therapy].
AB  - Dysmenorrhea (painful menstruation), which can be primary or secondary, is a
      common gynecological problem. Primary dysmenorrhea (normal gynecological finding)
      is caused by increased production of uterine prostaglandins. Namely, under the
      influence of hormonal changes and vegetative factors at the end of a menstrual
      cycle, in numerous girls and women with a normal gynecological finding,
      vasoconstriction in small uterine arteries and endometrial ischemia occur,
      resulting in excessive prostaglandins synthesis in endometrial cells. Local
      effect of prostaglandins on the uterus is manifested by painful uterine
      contractions during menstruation. Prostaglandins can cause general symptoms too
      (headache, nausea, vomiting, diarrhea, urinary frequency) because they are
      released from endometrial cells and they reach the systemic circulation
      (increased plasma levels of prostaglandins, particularly F2 alpha prostaglandin).
      Nonsteroidal anti-inflammatory drugs are established as initial therapy for women
      with primary dysmenorrhea; besides that, oral contraceptives and other
      prescription drugs are taken into consideration as well as different forms of
      complementary therapy. In 20-25% of cases, the reduction of pain is not achieved
      by use of standard therapy. Clinical experiences have shown that significant pain
      regression during a menstrual cycle has been often achieved by the use of spinal
      manipulative therapy (SMT) indicated in women with primary dysmenorrhea with
      coexisting functional disorders of lumbosacral (LS) spine. Namely, by activation
      of the nociceptive and vegetative system, LS spine disorders, before all
      segmental dysfunction and degenerative changes, can induce referred pain and
      reflex disturbances of pelvic organs (somatovisceral reflexes). Since significant
      improvement or disappearance of pain during a menstrual cycle is often achieved
      with adequate therapy of coexisting vertebral disorders in women with primary
      dysmenorrhea, it is important to recognise latent or manifest vertebral disorders
      in dysmenorrheic women using clinical examination.

PMID- 20030293
TI  - [Obesity as a medical and public health problem].
AB  - Obesity is one of the leading public health problems. Fat tissue is an organ with
      intensive metabolic activity whose function is to store unused energy. At the
      same time, it is a gland with internal secretion which secretes cytokines
      (adipokines) which have an endocrine, paracrine and autocrine function. Receptors
      for numerous hormones and cytokines are found on adipocytes. In such a way a
      functional connection between fat tissue and other tissues and organs is ensured.
      Fat tissue is part of a system of neuroendocrine regulation of body mass and
      metabolism. An increase in fat tissue, especially in visceral fat tissue, leads
      to an increase in adipokine blood concentration, which results in changes in the
      functioning of distant tissues and organs with which fat tissue is hormonally
      linked. The consequent comprehensive changes in the metabolism are termed
      metabolic syndrome, and are linked with further complications. The consequences
      of these complications are a diminished quality of life and a rise in mortality.
      The treatment of obesity is a long term and often unsuccessful process. Better
      results of treatment are achieved by a multidisciplinary approach.

PMID- 20030294
TI  - [Medical Association of the Croatian Coast and Gorski kotar].
AB  - In the Province Hospital Susak the Medical Association of the Croatian Coast and
      Gorski kotar was founded on October 2nd, 1936. At that time on the territory of
      the former District of Susak there were 59 physicians. The inauguration meeting
      was attended by 41 physicians and 26 of them voted for the autonomous Association
      rather than for one within the Croatian Medical Association of Zagreb. Vladimir
      Blaz, M.D. was the first elected president. During the Italian occupation in the
      2nd World War Association's activities were interrupted. After five years of
      inactivity, the Association was restored at its constituting session held on June
      8th, 1946, when Zdravko Kucic, M.D. was elected president. The Medical
      Association Rijeka-Susak was founded on September 24th, 1947 and the first
      elected president was Fran Bakarcic, M.D. It still kept functioning as an
      autonomous association. The following year the Association became the subsidiary
      of the Croatian Medical Association.

PMID- 20030295
TI  - [Algorithm of health care measures for elderly patients with headache].

PMID- 20030296
TI  - Bibliometric analysis of Chinese research on cyclization, MALDI-TOF, and
      antibiotics.
AB  - This paper reports a bibliometric analysis of the impact of research in China on
      cyclization, MALDI-TOF, and antibiotics, comparing this research with that in the
      USA, Germany, and Japan. It is shown that the productivity of the Chinese
      research (in terms of numbers of publications) is growing rapidly; however, this
      growth has not, to date, been accompanied by an analogous growth in impact (in
      terms of citations to the published work). A citation analysis of national and
      international collaboration patterns shows that collaborative research does not
      invariably result in a larger number of citations; in part, at least, this is
      shown to be due to the dominant role played by the publications of the Chinese
      Academy of Sciences.

PMID- 20030297
TI  - Computational study of the interactions between guanine derivatives and cyclin
      dependent kinase 2 (CDK2) by CoMFA and QM/MM.
AB  - Comparative molecular field analysis (CoMFA) and QM/MM hybrid calculations were
      performed on 9H-purine derivatives as CDK2 inhibitors. CoMFA was carried out to
      describe the activities of 78 analogues. The models were applied to a training
      set including 64 compounds. The best CoMFA model included steric and
      electrostatic fields, had a good Q(2) value of 0.845, and adequately predicted
      the compounds contained in the test set. Furthermore, plots of the steric CoMFA
      field allowed conclusions to be drawn for the choice of suitable inhibitors. In
      addition, the dynamical behavior of compounds with 4-(aminosulfonyl)phenyl, 4
      [(methylamino)sulfonyl]phenyl, 4-[(dimethylamino)sulfonyl]phenyl, and [3-methoxy
      4-(aminosulfonyl)]phenyl groups at position 2 of the 9H-purine scaffold inside
      the CDK2 active site were analyzed by QM/MM calculations. The interactions of
      these compounds with residues Lys89, Asp86, and Ile10 were characterized.

PMID- 20030299
TI  - Switchable wettability on cooperative dual-responsive poly-L-lysine surface.
AB  - A cooperative dual-responsive polypeptide surface switching between
      superhydrophilic and superhydrophobic states is presented. This macroscopic
      phenomenon of surface originates from the combination of the cooperative
      unfolding/aggregation of the poly-L-lysine (PLL) immobilized on the substrate
      with micro/nanocomposite structure in response to pH and temperature. At pH lower
      than the pK(a) of PLL (approximately 11.0), PLL mainly adopts a random coil
      conformation, which corresponds to the superhydrophilic state on the rough
      surface substrate. Raising the pH to higher than the pK(a) allows the appearance
      of alpha-helix conformation, which also corresponds to the hydrophilic state.
      However, heating up the surface at pH higher than the pK(a) destabilizes the
      alpha-helix conformation and induces the formation of aggregated beta-sheet
      structures, which represents the superhydrophobic state. Lowering the pH and
      temperature simultaneously switches a reversible conversion from superhydrophobic
      to superhydrophilic states. In the switching process, the hydrophobicity and
      hydrophilicity can be "memorized" due to the cooperative pH and temperature
      stimuli-induced unfolding/aggregation behaviors of PLL. This provides a new
      exciting prospect for understanding surface properties of polypeptides and the
      design of smart material surfaces with potential applications in nanodevices,
      bioseparation, and biosensors.

PMID- 20030298
TI  - Atom-centered interacting fragments and similarity search applications.
AB  - Parts of ligands in complex crystal structures that are involved in well-defined
      protein-ligand interactions are extracted and encoded as ensembles of atom
      centered fragments, termed atom-centered interacting fragments (AIFs), which
      implicitly capture three-dimensional interaction information. AIF reference sets
      are utilized for feature count-based ranking of databases to search for molecules
      having similar activity. AIF calculations are reported for eight enzyme targets
      with multiple crystallographic inhibitor complexes and, in addition, for a
      complex of a G protein coupled receptor with an antagonist. The AIF approach
      further increases compound recall of structural key-based fingerprints. Moreover,
      AIF combinations are found to be specific markers of different classes of active
      compounds that lead to an early enrichment of inhibitors and selective
      antagonists in similarity search calculations.

PMID- 20030300
TI  - Ultrafast light-driven nanomotors based on an acridane stator.
AB  - A series of molecular motors featuring a symmetrical acridane stator is reported.
      Photochemical and thermal isomerization experiments confirm that this stator, in
      combination with a thiopyran rotor, results in molecular rotary motion in which
      the rate-determining thermal helix inversion proceeds effectively only at
      temperatures above 373 K. The introduction of a cyclopentanylidene rotor unit
      results in a decrease in steric hindrance with respect to the stator, and as a
      consequence, a 10(12)-fold increase in the rate of thermal helix inversion is
      observed. Nanosecond transient absorption spectroscopy allows for the thermal
      processes to be followed accurately at ambient temperature. The rotary motor is
      shown to be able to operate at 0.5 MHz rotational frequencies under optimal
      conditions.

PMID- 20030301
TI  - Direct metalation of heteroaromatic esters and nitriles using a mixed lithium
      cadmium base. Subsequent conversion to dipyridopyrimidinones.
AB  - All pyridine nitriles and esters were metalated at the position next to the
      directing group using (TMP)(3)CdLi in tetrahydrofuran at room temperature. The 2
      , 3-, and 4-cyanopyridines were treated with 0.5 equiv of base for 2 h to afford,
      after subsequent trapping with iodine, the corresponding 3-iodo, 2-iodo, and 3
      iodo derivatives, respectively, in yields ranging from 30 to 61%. Cyanopyrazine
      was similarly functionalized at the 3 position in 43% yield. Ethyl 3
      iodopicolinate and -isonicotinate were synthesized from the corresponding
      pyridine esters in 58 and 65% yield. Less stable ethyl 4-iodonicotinate also
      formed under the same conditions and was directly converted to ethyl 4-(pyrazol-1
      yl)nicotinate in a two-step 38% yield. All three ethyl iodopyridinecarboxylates
      were involved in a one-pot palladium-catalyzed cross-coupling
      reaction/cyclization using 2-aminopyridine to afford new dipyrido[1,2-a:3',2'
      d]pyrimidin-11-one, dipyrido[1,2-a:4',3'-d]pyrimidin-11-one, and dipyrido[1,2
      a:3',4'-d]pyrimidin-5-one in yields ranging from 50 to 62%. A similar cross
      coupling/cyclization sequence was applied to methyl 2-chloronicotinate using 2
      aminopyridine, 2-amino-5-methylpyridine, and 1-aminoisoquinoline to give the
      corresponding tricyclic or tetracyclic compounds in 43-79% yield. Dipyrido[1,2
      a:4',3'-d]pyrimidin-11-one and dipyrido[1,2-a:3',4'-d]pyrimidin-5-one showed a
      good bactericidal activity against Pseudomonas aeroginosa . Dipyrido[1,2-a:2',3'
      d]pyrimidin-5-one and pyrido[2',3':4,5]pyrimidino[2,1-a]isoquinolin-8-one showed
      a fungicidal activity against Fusarium and dipyrido[1,2-a:4',3'-d]pyrimidin-11
      one against Candida albicans . Ethyl 4-(pyrazol-1-yl)nicotinate and dipyrido[1,2
      a:2',3'-d]pyrimidin-5-one have promising cytotoxic activities, the former toward
      a liver carcinoma cell line (HEPG2) and the latter toward a human breast
      carcinoma cell line (MCF7).

PMID- 20030302
TI  - Synthesis of chiral aminophosphines from chiral aminoalcohols via cyclic
      sulfamidates.
AB  - Protic aminophosphines with multiple chiral centers were synthesized in good
      yields and high purity by the nucleophilic ring-opening of N-protected cyclic
      sulfamidates with metal phosphides, followed by hydrolysis and deprotection. This
      synthetic approach is clean, scalable, and high yielding. The method provides an
      efficient alternative route for the synthesis of chiral aminophosphines.

PMID- 20030303
TI  - Efficient construction of five-membered aromatic and nonaromatic heterocycles
      from 1,6-enynes by a palladium-catalyzed domino coupling/cycloisomerization
      process.
AB  - General and efficient methods for the construction of five-membered aromatic and
      nonaromatic heterocycles by palladium-catalyzed coupling/cycloisomerization of
      1,6-enynes and aryl halides have been developed. Results indicate that
      substituents at the terminus of the alkynes have a significant effect on the
      selective formation of the products.

PMID- 20030304
TI  - Easy fabrication and resistivity-temperature behavior of an anisotropically
      conductive carbon nanotube-polymer composite.
AB  - An easy fabrication method comprising a slit die extrusion-hot stretch-quench
      process was used to make carbon nanotubes (CNTs) filled with anisotropically
      conductive polymer composite (ACPC). CNTs were first premixed with polycarbonate
      (PC) by coagulation and then melt mixed with polyethylene (PE). During extrusion,
      the CNT/PC/PE composite was subjected to hot stretching to make the CNT/PC phase
      form in situ an oriented conductive fibril assembly in the PE matrix. Finally the
      aligned CNT/PC short fibrils were quenched to preserve their structure. The
      resultant CNT/PC/PE composite exhibited strong anisotropy in conductivity. This
      method has the advantages of giving a highly oriented structure with good control
      of electrical anisotropy as well as the ability to be fabricated in a high rate
      manner. Temperature-resistivity behavior was investigated by observing the
      resistivity during isothermal treatment (IT) as well as nonisothermal treatment
      (NIT). Percolation behavior was seen in the isolated direction during the first
      IT at 180 degrees C. This was a result of a disordering-induced conductive
      network. In addition, the positive temperature coefficient (PTC) effect
      attenuated with IT duration. This was seen in contrast to the remaining negative
      temperature coefficient (NTC). The unique evolution of PTC and NTC effects
      originated from the ACPC's special conductive network. It can be seen that this
      is composed of the originally connected "intrinsic pathway" and isolated
      "potential pathway".

PMID- 20030305
TI  - FRET fluctuation spectroscopy of diffusing biopolymers: contributions of
      conformational dynamics and translational diffusion.
AB  - The use of fluorescence correlation spectroscopy (FCS) to study conformational
      dynamics in diffusing biopolymers requires that the contributions to the signal
      due to translational diffusion are separated from those due to conformational
      dynamics. A simple approach that has been proposed to achieve this goal involves
      the analysis of fluctuations in fluorescence resonance energy transfer (FRET)
      efficiency. In this work, we investigate the applicability of this methodology by
      combining Monte Carlo simulations and experiments. Results show that diffusion
      does not contribute to the measured fluctuations in FRET efficiency in conditions
      where the relaxation time of the kinetic process is much shorter than the mean
      transit time of the molecules in the optical observation volume. However, in
      contrast to what has been suggested in previous work, the contributions of
      diffusion are otherwise significant. Neglecting the contributions of diffusion
      can potentially lead to an erroneous interpretation of the kinetic mechanisms. As
      an example, we demonstrate that the analysis of FRET fluctuations in terms of a
      purely kinetic model would generally lead to the conclusion that the system
      presents complex kinetic behavior even for an idealized two-state system.

PMID- 20030306
TI  - Mutation screening based on the mechanical properties of DNA molecules tethered
      to a solid surface.
AB  - We report a rapid gene mutation screening method by making use of the mechanical
      properties of single-strand DNA (ssDNA) tethered to a solid surface. With proper
      temperature control, ssDNA in solution undergoes intrabase pairing and forms a
      specific complex 3D structure. By tethering such ssDNA strands to a solid
      surface, a DNA film can be formed. The mechanical properties of such DNA films,
      probed by devices such as a quartz crystal resonator, are directly related to the
      specific structure of the ssDNA which is characteristic of its base sequence and
      thus can be used as the basis for mutation screening. Using this approach, we
      have detected a single base mutation among 545 bases in the P53 gene. This result
      suggests promising potential of employing the mechanical properties of DNA
      strands for rapid screening of mutations.

PMID- 20030307
TI  - Relative complexation energies for Li(+) ion in solution: molecular level
      solvation versus polarizable continuum model study.
AB  - Relative complexation energies for the lithium cation in acetonitrile and diethyl
      ether have been studied. Quantum-chemical calculations explicitly describing the
      solvation of Li(+) have been performed based on structures obtained from
      molecular dynamics simulations. The effect of an increasing number of solvent
      molecules beyond the first solvation shell has been found to consist in reduction
      of the differences in complexation energies for different coordination numbers.
      Explicit-solvation data have served as a benchmark to the results of polarizable
      continuum model (PCM) calculations. It has been demonstrated that the PCM
      approach can yield relative complexation energies comparable to the predictions
      based on molecular-level solvation, but at significantly lower computational
      cost. The best agreement between the explicit-solvation and the PCM results has
      been obtained when the van der Waals surface was adopted to build the molecular
      cavity.

PMID- 20030308
TI  - Effects of the polymorphic transformation of glutaric acid particles on their
      deliquescence and hygroscopic properties.
AB  - The effects of the polymorphism of glutaric acid (GA) particles on their
      deliquescence properties at room temperature were studied. The polymorphic states
      of GA, including the metastable alpha-form and the thermodynamically stable beta
      form, were characterized by Raman spectral measurements. The deliquescence of GA
      particles was also studied by Raman and optical observations. It was found that
      the alpha-form deliquesced at 85-86% relative humidity (RH), whereas some alpha
      form transformed to the beta-form rather than completing full deliquescence. The
      beta-form absorbed water slowly at 87-89% RH, which was higher than the
      deliquescence relative humidity (DRH) of the alpha-form. The water-uptake process
      was not completed in 5 h, but the particles deliquesced quickly (<15 min) when
      the RH was increased to about 90%, indicating that mass transfer was delayed in
      the beta-form and that a higher RH of 90% was needed to cross the kinetic
      barrier. We showed that polymorphic transformation alters the deliquescence
      properties of GA particles, which might explain the discrepancies in DRH values
      of GA particles (83-90%) reported in the literature. This transformation should
      be taken into account in future laboratory experiments and aerosol thermodynamic
      models.

PMID- 20030309
TI  - Online high-performance size exclusion chromatography-nuclear magnetic resonance
      for the characterization of dissolved organic matter.
AB  - The substantial heterogeneity of dissolved organic matter (DOM) inhibits detailed
      chromatographic analysis with conventional detectors as little structural
      information can be obtained in the presence of extensive coelution. Here we
      examine the direct hyphenation of high-performance size exclusion chromatography
      (HPSEC) with nuclear magnetic resonance (NMR) spectroscopy to determine how size
      distinguished fractions differ in composition. The results support the
      applicability of using HPSEC to generate more homogeneous fractions of DOM prior
      to NMR analysis and demonstrate that structure is significantly altered with
      size. The largest fractions are enriched in carbohydrate- and aromatic-type
      structures. The midsized material is substantial and is representative of
      carboxyl-rich alicyclic molecules (CRAMs). The smallest material has strong
      signatures of material derived from linear terpenoids (MDLT). Both CRAMs and MDLT
      have been recently hypothesized as major components of DOM, and detection by
      HPSEC-NMR confirms their existence as unique and separable entities. This
      preliminary work focuses on NMR hyphenation to HPSEC due to widespread use of
      HPSEC to characterize DOM. Online hyphenation is useful not only for time
      efficient analysis of DOM but also for that of other highly complex samples such
      as those found in many environmental analyses.

PMID- 20030310
TI  - Thickness-dependent morphologies of gold on n-layer graphenes.
AB  - We report that gold thermally deposited onto n-layer graphenes interacts
      differently with these substrates depending on the number layer, indicating the
      different surface properties of graphenes. This results in thickness-dependent
      morphologies of gold on n-layer graphenes, which can be used to identify and
      distinguish graphenes with high throughput and spatial resolution. This technique
      may play an important role in checking if n-layer graphenes are mixed with
      different layer numbers of graphene with a smaller size, which cannot be found by
      Raman spectra. The possible mechanisms for these observations are discussed.

PMID- 20030311
TI  - Calcium precursors for the production of CaO sorbents for multicycle CO2 capture.
AB  - A screening of potential calcium precursors for the production of CaO sorbents
      for CO(2) capture at high temperature was conducted in this work. The precursors
      studied include microsized calcium carbonate (CC-CaO), calcium hydroxide (CH
      CaO), nanosized (<70 nm) calcium carbonate (CC70 nm-CaO), nanosized (<160 nm)
      calcium oxide (CaO160 nm-CaO), calcium acetate hydrate (CA-CaO), calcium l
      lactate hydrate (CL-CaO), calcium formate (CF-CaO), calcium citrate tetrahydrate
      (CCi-CaO), and calcium d-gluconate monohydrate (CG-CaO). The capture capability
      of these sorbents was investigated using a thermogravimetric analyzer (TGA) for
      multiple capture cycles. CG-CaO exhibited the best capacity for capturing CO(2)
      with a 1-min conversion of 65.9% and a 30-min conversion of 83.8% at the ninth
      cycle. Subsequently, a further parametric study was conducted to examine the
      effect of reaction conditions such as reaction temperature (550-750 degrees C)
      and CO(2) gas concentration (1-15%) on the capture capacity of CG-CaO. The
      sorbent CG-CaO also showed a much lower decomposition temperature and higher
      predicted residual conversion after prolonged cycles, compared with CC-CaO.

PMID- 20030312
TI  - Combining aurophilic interactions and halogen bonding to control the luminescence
      from bimetallic gold-silver clusters.
AB  - The luminescence in a series of new bimetallic gold-silver vapochromic structures
      can be efficiently switched among different colors simply by exposure to solvent
      vapors. The emission color in these systems is controlled by both aurophilic
      interactions and halogen bonding, which affect the emission energy through
      different orbitals.

PMID- 20030313
TI  - Preparation of cyclonucleosides.

PMID- 20030314
TI  - Metal cation mediated-capillary electrophoresis of nucleic acids.
AB  - Nucleic acid electrophoresis separation heavily depends upon gel or nongel
      sieving matrix. Here we propose a metal ion mediated-capillary electrophoresis
      (MCE-CE) by utilizing the nonspecific interactions of Mg(2+) and Ca(2+) and
      demonstrate the size, conformation, or sequence based separation and
      characterization of versatile nucleic acid molecules in free solution. Mg(2+) and
      Ca(2+) can induce DNA separation at the concentrations as low as 100 and 50 muM,
      respectively. Noteworthy, the two naturally occurring polymorphisms of one base
      substitution that may change the secondary folding structure or base stacking can
      be discriminated by MCM-CE, showing its unique capability of resolving length
      identical but conformation-different ssDNA. Benefiting from the achieved
      separation, we further demonstrate that the folding conformation of oligomers and
      its change caused by single base substitution can be promptly sensed by online
      coupled fluorescence polarization. We anticipate that this method will be
      applicable in length polymorphism analysis, single-strand polymorphism analysis,
      hybridization analysis, microRNA analysis, and study of protein-nucleic acid
      interactions and the conformation-function relationship.

PMID- 20030315
TI  - Total synthesis and absolute configuration of (-)-berkeleyamide A.
AB  - A chiral-pool approach to (-)-berkeleyamide A 1 based on a diastereoselective
      nitrile oxide [3 + 2]-cycloaddition completes the first total synthesis
      establishing the absolute stereochemistry of the natural product.

PMID- 20030316
TI  - Enamine-iminium ion Nazarov cyclization of alpha-ketoenones.
AB  - The mono-triflate salts of some chiral nonracemic 1,2-diamines react with alpha
      ketoenones in a stoichiometric reaction to form products of the Nazarov
      cyclization in high enantiomeric ratios. The mechanism appears to involve
      rearrangement of an enamine-iminium ion.

PMID- 20030317
TI  - One-pot highly diastereoselective synthesis of cis-vinylaziridines via the sulfur
      ylide-mediated aziridination and palladium(0)-catalyzed isomerization.
AB  - Highly diastereoselective synthesis of cis-trisubstituted vinylaziridines
      containing a quaternary carbon center is realized by a one-pot protocol in which
      the combination of sulfur ylide-mediated aziridination of cyclic ketimines and
      Pd(0)-catalyzed isomerization is employed successfully.

PMID- 20030318
TI  - Thermal and pH stability of betacyanin pigment of Djulis (Chenopodium formosanum)
      in Taiwan and their relation to antioxidant activity.
AB  - The betacyanin pattern of Djulis (Chenopodium fromosanum), a native cereal plant
      in Taiwan, was reported for the first time. The determination of characteristics
      of the pigment, including pH and thermal stability and their relation to
      antioxidant activities, indicated that betacyanin of Djulis exhibited the maximum
      absorbance at 530 nm and their thermal stability was dependent on the pH.
      Antioxidant capacities as well as red color of that pigment were significantly
      positively related with A(530). Therefore, A(530) can be used as a simple index
      of the antioxidant capacity of that pigment. Four peaks including betanin
      (47.8%), isobetanin (30.0%) with m/z 551.0, and armaranthin (13.6%),
      isoamaranthinee (8.6%) with m/z 727.0 were purified from the pigment extract by
      HPLC and identified through LC/MS. Among them, betanin and isobetanin totally
      accounted for more than 70% of FRAP reducing power or DPPH scavenging capacity
      and were a major source of the antioxidant capacities. Our findings of this
      pigment confirmed that Djulis can be used as a novel source of betanin
      antioxidants and may provide a basis for its sustainable utilization in the food
      industry.

PMID- 20030319
TI  - Simple synthesis of clay-gold nanocomposites with tunable color.
AB  - Clay-based nanocomposites have been studied for several decades, mainly focusing
      on clay-polymer nanocomposites. Here, we report on a simple wet chemical method
      to synthesize clay-APTES-Au (CAAu) nanocomposites, where 3
      aminopropyltriethoxysilane (APTES) acts as the linkage. The silane terminal of
      APTES formed bonds with the clay surface, while the other -NH(2) terminal bonds
      to gold nanoparticles. The color of clay changed when these CAAu nanocomposites
      were formed. By changing the size of the gold nanoparticles, the color of CAAu
      could be adjusted, simply by changing process parameters. TEM characterization of
      the synthesized nanocomposites showed an even distribution of gold nanoparticles
      on the clay surfaces. The nanocomposites were stable in strong acid and high
      concentration of salt conditions, while strong basic solution like NaOH could
      slightly influence the status of the gold nanoparticles due to the rupture of the
      Si-O-Si bonds between APTES and clay. To demonstrate the potential for label free
      sensing application of CAAu nanocomposites, we made hybrids of clay-APTES-Au-HD
      Au (CAAuHAu), where hexamethylene diamine (HD) served as links between CAAu
      nanocomposites and the gold nanoparticles. The color of the composites changed
      from red to blue, when the hybrids were formed. Moreover, hemoglobin was loaded
      on the CAAu nanocomposites, which can potentially be used as a biosensor. These
      synthesized nanocomposites may combine the catalytic properties of clay and the
      well-known excellent properties of gold nanoparticles, such as the ability to
      anchor biological and chemical molecules. Furthermore, the color change of CAAu,
      when the CAAuHAu hybrids were observed, suggests the applications of these
      nanocomposites in biochemical and chemical sensing.

PMID- 20030320
TI  - Development of a poly(d,l-lactic-co-glycolic acid) nanoparticle formulation of
      STAT3 inhibitor JSI-124: implication for cancer immunotherapy.
AB  - Constitutively activated signal transducer and activator of transcription-3
      (STAT3) in tumor and dendritic cells (DCs) plays a critical role in tumor-induced
      immunosuppression. This is considered a major challenge in effective
      immunotherapy of cancer. Herein we describe the development of a polymeric
      nanocarrier for the delivery of JSI-124 (a small molecule inhibitor of STAT3) to
      tumor and immunosuppressed DCs using poly(d,l-lactic-co-glycolic acid)
      nanoparticles (PLGA NPs). For this purpose, JSI-124 was chemically conjugated to
      PLGA and the PLGA-JSI-124 conjugate was formulated into nanoparticles using the
      emulsification solvent evaporation method. The attachment of JSI-124 to PLGA was
      confirmed by a combination of thin layer chromatography and (1)H NMR. The level
      of JSI-124 in NPs, determined by liquid chromatography-mass spectrometry, was
      found to be 1.7 +/- 0.3 microg per mg of PLGA. The PLGA-JSI-124 NPs demonstrated
      a controlled drug release profile over a 1-month period and exhibited potent
      anticancer and STAT3 inhibitory activity comparable to the soluble JSI-124 after
      24 h incubation with B16 melanoma cells, in vitro. Moreover, PLGA-JSI-124 NPs
      efficiently suppressed the level of p-STAT3 in p-STAT3(high) DCs, generated from
      mouse bone marrow cells in the presence of conditioned media of B16 cells (B16CM
      DCs), and improved their function as assessed by mixed lymphocyte reaction (MLR).
      Specifically cotreatment of B16CM-DCs with PLGA-JSI-124 NPs and PLGA NPs
      containing the DC adjuvant CpG resulted in higher levels of T cell proliferation
      in the MLR assay compared with B16CM-DCs untreated or treated with either CpG NPs
      or JSI-124 NPs alone. Our results indicate that PLGA NPs containing conjugated
      JSI-124 can potentially provide a useful platform for sustained JSI-124 release
      in tumor and its targeted delivery to DCs leading to the modulation of anticancer
      response by JSI-124 in tumor cells and immunosuppressed DCs, in vitro.

PMID- 20030321
TI  - Simultaneous optical and electrical single channel recordings on a PEG glass.
AB  - Single molecule imaging of working ion-channels is much more difficult than that
      of water-soluble proteins because of the fragile nature of membranes and lateral
      diffusion of particles in the membranes, which does not allow fluorescent
      contamination for optical single channel recording. In this report, we
      reconstituted maxi-potassium channels from porcine uterine smooth muscle into
      artificial planar bilayers formed on poly(ethylene glycol) (PEG) modified glass
      and performed simultaneous optical and electrical recording of the single
      channels. The channels were immobilized in the membranes by anchoring to PEG
      molecules on the glass. The technique developed in this study should pave the way
      for single molecule pharmacology of ion-channels.

PMID- 20030322
TI  - Shape and size controlled synthesis of anatase nanocrystals with the assistance
      of ionic liquid.
AB  - We report an ionic liquid (IL) assisted hydrothermal method to synthesize anatase
      TiO(2) nanocrystals (NCs), in which TiCl(4) was used as precursor, 1-butyl-3
      methylimidazolium chloride (bmim(+)Cl(-)) as IL, and F(-) or SO(4)(2-) ions as
      phase transformation inhibitor. The surfactant-like nature of IL was found to
      play a key role in controlling the crystallization process via controlling the
      aggregation manner of the NCs. The fine-tuning abilities of the operating
      parameters of the bmim(+)Cl(-)/TiCl(4)/H(2)O system facilitated the controlling
      over the shape and size of TiO(2) NCs. Phase-pure anatase monodisperse NCs with
      various shape and size were controllably obtained. Moreover, the aggregation
      manners of anatase NCs were also studied, and it was demonstrated that the high
      concentration of HF or H(2)SO(4) could result in aggregation of anatase NCs to
      form pseudo single crystals.

PMID- 20030323
TI  - Photocatalytic coalescence of functionalized gold nanoparticles.
AB  - A novel strategy for the synthesis of chromophore-functionalized AuNPs with a
      narrow size distribution is reported. It consists of increasing the size of
      preprepared NPs by means of a fast (second scale) and clean (light and an organic
      photocatalyst) method. The results agree with thiolate ligand liberation from the
      NP surface promoted by photogenerated radicals. This lets gold cores come
      together and finally coalesce.

PMID- 20030324
TI  - Differentiating oxicam nonsteroidal anti-inflammatory drugs in phosphoglyceride
      monolayers.
AB  - Meloxicam, piroxicam, and tenoxicam belong to a highly potent oxicam group of
      nonsteroidal anti-inflammatory drugs. Whereas the structurally similar oxicams
      have different pharmacokinetics, treatment efficiency, and adverse effects, their
      common mechanism of action is the inhibition of a membrane enzyme,
      cyclooxygenase. Because the prerequisite for accessing the cyclooxygenase by the
      drugs is interaction with the membrane, the focus of the current study was a
      comparison of how meloxicam, piroxicam, and tenoxicam interact with lipid
      monolayers used as models of biological membranes. The monolayers were formed
      with 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol), 1,2-dipalmitoyl-sn
      glycero-3-phospho-l-serine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2
      dipalmitoyl-sn-glycero-3-phosphoethanolamine, 1,2-myristoyl-sn-glycero-3
      phosphoethanolamine, and 1,2-dilauroyl-sn-glycero-3-phosphoethanolamine. These
      systems were examined via surface pressure and surface electrical potential
      measurements, polarization modulation infrared reflection adsorption spectra, and
      Brewster angle microscopy. The three oxicams are differentiated in the
      monolayers; meloxicam shows the highest ability to modify membrane fluidity and
      surface potential, followed by piroxicam and tenoxicam. The dissimilarity of the
      biological activity of the oxicams may be linked to different interaction with
      the membrane, as revealed by the present study.

PMID- 20030325
TI  - Uptake and metabolism of new synthetic lipophilic derivatives, hydroxytyrosyl
      ethers, by human hepatoma HepG2 cells.
AB  - As a response to the increasing demand by the food industry for new synthetic
      lipophilic antioxidants, hydroxytyrosyl methyl, ethyl, propyl and butyl ethers
      have been synthesized from hydroxytyrosol, with similar or even higher
      antioxidant activity than free hydroxytyrosol. The uptake and metabolism of
      hydroxytyrosyl ethers with different alkyl side chain lengths (methyl, ethyl,
      propyl, and butyl) was studied after incubation for 2 and 18 h with HepG2 cells
      as a model of the human liver. LC-DAD and LC-MS were used for the identification
      of metabolites in culture media, cell lysates and samples hydrolyzed with beta
      glucuronidase and sulfatase. In vitro conjugation reactions of pure phenols were
      also performed. The results show an extensive uptake and metabolism by HepG2
      cells after 18 h of incubation. A direct relationship between the lipophilic
      nature of the compound and the biotransformation yield was observed. Similar
      ratio of methyl and glucuronide forms were detected after 2 h of incubation while
      at 18 h high amounts of methylglucuronides and glucuronide metabolites were
      identified together with low amounts of methyl conjugates. In conclusion, alkyl
      hydroxytyrosyl ethers could be metabolized by the liver, their metabolic rate
      being higher for the more lipophilic compounds.

PMID- 20030326
TI  - Microstructure and ultrastructure of high-amylose rice resistant starch granules
      modified by antisense RNA inhibition of starch branching enzyme.
AB  - A high-amylose transgenic rice line (TRS) modified by antisense RNA inhibition of
      starch branching enzymes revealed a resistant starch-rich quality. Compound
      starch granules in whole grains of the regular rice cultivar Teqing (TQ) were
      readily split during fracturing, whereas the starch granules in TRS were
      structurally intact and showed large voluminous, non-angular rounded bodies and
      elongated, filamentous structures tolerant of fracturing. In isolated
      preparation, TQ starch granules broke up into separate polygonal granules,
      whereas TRS starch granules kept their intactness. TRS starch granules consisted
      of packed smaller subgranules, some of which located at the periphery of starch
      granules were fused to each other with adjacent ones forming a thick band or wall
      encircling the entire circumference of the granules. TQ starch granules had a
      high concentration of amylose in the concentric hilum, whereas TRS starch
      granules showed a relatively even distribution of amylose with intense amylose in
      both hilum and band.

PMID- 20030327
TI  - Isolation and structural characterization of two new metabolites from monascus.
AB  - Two new pale yellow metabolites have been isolated from commercially available
      Chinese food additive Red Monascus Pigment and from Monascus ruber culture broth.
      They were isolated by successive TLC and semipreparative HPLC. Their structural
      characterization was elucidated by a variety of spectroscopic techniques (UV, IR,
      NMR) and mass spectrometry. These two new metabolites present numerous
      similarities with monascorubrin and rubropunctatin, differing in their structure
      only by the absence of the lactone ring. High-resolution mass spectrometry
      indicated the molecular formulas C(20)H(26)O(4) and C(22)H(30)O(4). The new
      compounds, named monarubrin and rubropunctin, contain a propenyl group on a
      pyrone ring, an alkyl side chain, but no gamma-lactone ring. The new metabolites
      have the property of producing strong blue fluorescence at 340 nm.

PMID- 20030328
TI  - Isoegomaketone inhibits lipopolysaccharide-induced nitric oxide production in RAW
      264.7 macrophages through the heme oxygenase-1 induction and inhibition of the
      interferon-beta-STAT-1 pathway.
AB  - Isoegomaketone (IK) is an essential oil component of Perilla frutescens (L.)
      Britt., and there have been no studies investigating its biological activities.
      We found that IK inhibits lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production in RAW 264.7 macrophages, and moreover, when IK was injected into
      animals prior to LPS administration, NO serum levels decreased in a dose
      dependent manner. These results indicate that IK possesses anti-inflammatory
      activity both in vitro and in vivo. IK suppressed the phosphorylation of STAT-1
      and the production of IFN-beta. Treatment with IK also inhibited the activation
      of NF-kappaB and activator protein-1, but more IK was required for inhibition
      than for STAT-1 inhibition, indicating that downregulation of inducible nitric
      oxide synthase gene expression by IK is mainly attributed to the blockade of STAT
      1 activation. Furthermore, IK also induced the expression of heme oxygenase-1 (HO
      1) through the activation of nuclear factor E2-related factor 2. Treatment with
      SnPP, a selective inhibitor of HO-1, reversed the IK-induced suppression of STAT
      1 phosphorylation and NO production. Taken together, IK isolated from P.
      frutescens inhibits NO production in LPS-treated RAW 264.7 macrophages through
      simultaneous induction of HO-1 and inhibition of the IFN-beta-STAT-1 pathway.

PMID- 20030329
TI  - Quantification of xylitol in foods by an indirect competitive immunoassay.
AB  - Sugar alcohols are widely used as food additives and drug excipients. d-Xylitol
      (INS 967), an important five-carbon sugar alcohol, is a natural constituent of
      many fruits and vegetables. The critical reagent for an immunoassay of haptens is
      the requirement of hapten-specific antibodies. Here, affinity-purified xylitol
      specific antibodies generated earlier [Sreenath, K.; Venkatesh, Y. P. Reductively
      aminated D-xylose-albumin conjugate as the immunogen for generation of IgG and
      IgE antibodies specific to D-xylitol, a haptenic allergen. Bioconjugate Chem.
      2007, 18, 1995-2003] have been utilized for developing an indirect competitive
      ELISA for xylitol. With xylitol-BSA conjugate as the coating antigen, a working
      range of 5-400 ng of xylitol could be determined in the immunoassay; the limit of
      detection was 1 ng of xylitol. Onion (Allium cepa) and strawberry (Fragaria
      nilgerrensis) were selected as the food sources containing D-xylitol. The amount
      of D-xylitol was found to be 12.6 and 44 mg/100 g fresh weight of onion and
      strawberry, respectively, and the results are in good agreement with the reported
      values by HPLC and GC. The recovery analyses showed that added amounts of D
      xylitol were recovered fairly accurately with recoveries in the range of 89.2 to
      94.9% in the case of onion, and 88.4 to 95.9% in the case of strawberry. The
      indirect competitive ELISA for xylitol quantification is a simple method using a
      3 kDa ultrafiltrate of whole food extract, and does not require extensive sample
      preparation and derivatization as in the case of GC and HPLC analyses. This is
      the first immunoassay developed for the sugar alcohol, xylitol.

PMID- 20030331
TI  - Reductive and transition-metal-free: oxidation of secondary alcohols by sodium
      hydride.

PMID- 20030330
TI  - Anthocyanin absorption, metabolism, and distribution from a wild blueberry
      enriched diet (Vaccinium angustifolium) is affected by diet duration in the
      Sprague-Dawley rat.
AB  - The effect of wild blueberry consumption on anthocyanin (ACNs) distribution and
      metabolism in Sprague-Dawley (SD) rats was investigated. Thirty-two rats were fed
      for 4 or 8 weeks with a control (C) or a wild blueberry-enriched diet (8%) (WB).
      Anthocyanin profile in plasma, urine, feces, brain, and liver was evaluated by LC
      MS/MS, and significantly increased in urine and not in feces after 8 weeks on the
      WB diet compared to that in 4 weeks, but no anthocyanins were detected in plasma,
      liver, and brain samples either in the C or WB groups. Metabolites of ACNs were
      detected in the plasma, urine, feces, and tissues of both the C and WB groups,
      but the urinary excretion of hippuric acid increased significantly after 4 and 8
      weeks of WB consumption. Thus, it seems that ACNs are metabolized by the
      intestinal microflora to respective phenyl-alkyl acids, which can be further
      metabolized to benzoic acid. In conclusion, ACNs are bioavailable in rats, and
      the extent of their metabolism and excretion is based on diet duration.
      Additionally, urinary hippuric acid content could represent a potential biomarker
      of ACNs absorption and metabolism in the SD rat under the present experimental
      conditions.

PMID- 20030332
TI  - Femto liquid chromatography with attoliter sample separation in the extended
      nanospace channel.
AB  - A liquid chromatography system, comprising a separation column with a width and
      depth of a few hundred nanometers, was fabricated on a glass microchip (femto
      liquid chromatography, fLC). The size of this system was approximately 10(11)
      times smaller than that of a conventional LC system, the flow rate was
      subpicoliter/minute, and the injection volume was a few hundred attoliters. The
      fLC system did not require packing stationary phase and was capable of separating
      solutes with different molecular charges (fluorescein and sulforhodamine B) that
      could not be separated on a conventional LC column whose surface was covered with
      the same functional group as that of the column of the fLC system. The fLC system
      represented herein overcomes limitations of conventional chromatography
      separation, namely, heterogeneity of the stationary phases and eddy diffusion.
      Scale-down of the chromatography system brought advantages not only in reduction
      of sample volume but also in separation efficiency. The fLC system can analyze a
      very small amount of sample with high efficiency and will be useful in analyzing
      small samples, such as single cells and synaptic clefts. fLC greatly influences
      and benefits various fields such as life sciences, medicine, environmental
      science, and manufacturing by the improvement of separation technology.

PMID- 20030333
TI  - Finding out egyptian gods' secret using analytical chemistry: biomedical
      properties of egyptian black makeup revealed by amperometry at single cells.
AB  - Lead-based compounds were used during antiquity as both pigments and medicines in
      the formulation of makeup materials. Chemical analysis of cosmetics samples found
      in Egyptians tombs and the reconstitution of ancient recipes as reported by Greco
      Roman authors have shown that two non-natural lead chlorides (laurionite Pb(OH)Cl
      and phosgenite Pb(2)Cl(2)CO(3)) were purposely synthesized and were used as fine
      powders in makeup and eye lotions. According to ancient Egyptian manuscripts,
      these were essential remedies for treating eye illness and skin ailments. This
      conclusion seems amazing because today we focus only on the well-recognized
      toxicity of lead salts. Here, using ultramicroelectrodes, we obtain new insights
      into the biochemical interactions between lead(II) ions and cells, which support
      the ancient medical use of sparingly soluble lead compounds. Submicromolar
      concentrations of Pb(2+) ions are shown to be sufficient for eliciting specific
      oxidative stress responses of keratinocytes. These consist essentially of an
      overproduction of nitrogen monoxide (NO degrees ). Owing to the biological role
      of NO degrees in stimulating nonspecific immunological defenses, one may argue
      that these lead compounds were deliberately manufactured and used in ancient
      Egyptian formulations to prevent and treat eye illnesses by promoting the action
      of immune cells.

PMID- 20030334
TI  - Genetically engineered clostridial C2 toxin as a novel delivery system for living
      mammalian cells.
AB  - The C2 toxin of Clostridium botulinum is a binary bacterial protein toxin,
      comprising the enzyme component C2I and the separate binding/translocation
      component C2IIa. C2IIa mediates the transport of C2I into the host cell cytosol.
      The N-terminal domain of C2I (C2IN) is enzymatically inactive but essential for
      C2IIa-mediated internalization of C2I. Here, we exploit the C2IIa/C2IN system to
      generate a recombinant C2IN-streptavidin fusion protein allowing for the delivery
      of biotinylated molecules into the cytosol of mammalian cells. C2IN-streptavidin
      overproduced in E. coli was affinity-purified and capable of binding biotinylated
      proteins in a concentration-dependent manner. Real-time surface plasmon resonance
      confirmed the biotin-mediated interaction yielding a K(D)-value of approximately
      0.75 muM. Internalization of C2IN-streptavidin into the cytosol of epithelial
      cells and macrophages was demonstrated by immunoblot analysis and confirmed by
      confocal microscopy. Cell viability studies showed no cytotoxic effects of the
      novel transporter. Furthermore, Vero cells treated with biotin-fluorescein or
      biocytin-Alexa488 as model cargo displayed a specific C2IN-streptavidin/C2IIa
      dependent uptake, providing proof-of-principle for the functionality of this
      novel delivery system.

PMID- 20030335
TI  - Photoelectrochemical characterization of a robust TiO2/BDD heterojunction
      electrode for sensing application in aqueous solutions.
AB  - Titanium dioxide (TiO(2)) and boron-doped diamond (BDD) are two of the most
      popular functional materials in recent years. In this work, TiO(2) nanoparticles
      were immobilized onto the BDD electrodes by a dip-coating technique. Continuous
      and uniform mixed-phase (anatase and rutile) and pure-anatase TiO(2)/BDD
      electrodes were obtained after calcination processes at 700 and 450 degrees C,
      respectively. The particle sizes of both types of TiO(2) film range from 20 to 30
      nm. In comparison with a TiO(2)/indium tin oxide (ITO) electrode, the TiO(2)/BDD
      electrode demonstrates a higher photoelectrocatalytic activity toward the
      oxidation of organic compounds, such as glucose and potassium hydrogen phthalate.
      Among all the tested TiO(2) electrodes, the mixed-phase TiO(2)/BDD electrode
      demonstrated the highest photoelectrocatalytic activity, which can be attributed
      to the formation of the p-n heterojunction between TiO(2) and BDD. The electrode
      was subsequently used to detect a wide spectrum of organic compounds in aqueous
      solution using a steady-state current method. An excellent linear relationship
      between the steady-state photocurrents and equivalent organic concentrations was
      attained. The steady-state oxidation photocurrents of the mixed-phase TiO(2)/BDD
      electrode were insensitive to pH in the range of pH 2-10. Furthermore, the
      electrodes exhibited excellent robustness under strong acidic conditions that the
      TiO(2)/ITO electrodes cannot stand. These characteristics bestow the mixed-phase
      TiO(2)/BDD electrode to be a versatile material for the sensing of organic
      compounds.

PMID- 20030336
TI  - Label-free and real-time sequence specific DNA detection based on supramolecular
      self-assembly.
AB  - A new label-free, optical method was developed to detect sequence-specific DNA
      based on supramolecular self-assembly. A cationic phenylene ethynylene oligomer
      with two pairs of positively charged side chains (OPE-2) can form a J-dimer or J
      aggregate with negatively charged DNA by a combination of electrostatic and
      hydrophobic interactions. At microM concentrations of dsDNA (number of bases in
      ssDNA ranges from 8 to 32), the optimum supramolecular self-assembly occurs
      between OPE-2 and dsDNA and is characterized by a new absorption peak emerging at
      418 nm and an increase in fluorescence intensity (about 4.5-fold for dsDNA(1)).
      In contrast, the self-assembled complexes between OPE-2 and ssDNA are less
      readily formed under the same conditions. Interestingly, the induced circular
      dichroism (CD) signal for OPE-2/ssDNA is quite strong, likely owing to the self
      assembly onto ssDNA simultaneously templating helix formation. In contrast, the
      induced CD signal for OPE-2/dsDNA is weak, likely because the dsDNA is in a
      double helix conformation, and OPE-2 associated with the dsDNA should be outside
      of the helix. In fact, there is a steady decrease in the induced CD signal for
      ssDNA with the addition of equimolar complementary ssDNA over time that allows
      the monitoring of DNA hybridization in real time. Introduction of mismatched
      bases into the target DNA sequence prevents the full hybridization between ssDNA
      and the target DNA. For these cases, the decrease in the induced CD signals
      occurs more slowly and to a lesser extent, as some of the unhybridized portions
      may remain in helical association with OPE-2. In view of these observed signal
      changes, sequence specific DNA and single nucleotide mismatch can be detected in
      a very simple and sensitive manner without any modification of the DNA.

PMID- 20030337
TI  - Magnetic ordering in nitrides with the eta-carbide structure,
      (Ni,Co,Fe)2(Ga,Ge)Mo3N.
AB  - Compositions in the series Ni(2-x)Co(x)GeMo(3)N (0 < or = x < or = 2), Co(2)Ge(1
      x)Ga(x)Mo(3)N (0 < x < or = 0.7), Co(2-x)Fe(x)GeMo(3)N (0 < or = x < or = 2), and
      Co(2-x)Fe(x)Ge(0.5)Ga(0.5)Mo(3)N (0 < or = x < or = 0.8) have been synthesized by
      the reductive nitridation of binary oxides and studied by appropriate
      combinations of magnetometry, transport measurements, neutron diffraction, and
      Mossbauer spectroscopy. All of these compositions adopt the cubic eta-carbide
      structure (a approximately 11.11 A) and show a resistivity of approximately 10(
      3) Omega cm. No long-range magnetic order was observed in Ni(2-x)Co(x)GeMo(3)N,
      although evidence of spin freezing was observed in Co(2)GeMo(3)N. The
      introduction of gallium into this composition leads to the onset of
      antiferromagnetic ordering at 90 K in Co(2)Ge(0.3)Ga(0.7)Mo(3)N. The magnetic
      structure consists of an antiferromagnetic arrangement of ferromagnetic Co(4)
      groups, with an ordered magnetic moment of 0.48(9) micro(B) per cobalt atom. The
      same magnetic structure is found in Co(0.5)Fe(1.5)GeMo(3)N and
      Co(1.2)Fe(0.8)Ge(0.5)Ga(0.5)Mo(3)N. The former orders above room temperature with
      an average moment of 1.08(3) mu(B) per transition-metal site, and the latter at
      228 K with an average moment of 1.17(4) micro(B) per site. The magnetic behavior
      of these compounds is discussed in terms of the electron count within each
      series.

PMID- 20030338
TI  - Fate of beta blockers in aquatic-sediment systems: sorption and
      biotransformation.
AB  - The fate of beta blockers (atenolol, acebutolol, bisoprolol, celiprolol,
      metoprolol, nadolol, pindolol, propranolol, and sotalol) was studied in surface
      water-sediment systems. A new analytical method was developed to determine the
      beta blockers in sediments by LC-ESI-tandem MS detection. The relative recoveries
      in sediments ranged from 89 +/- 7% (acebutolol) to 102 +/- 3% (nadolol) using
      deuterated surrogate standards. Beta blockers were present with concentrations up
      to 86 ng/g (bisoprolol) in the sediments of small German streams containing an
      elevated percentage of treated wastewater. Biotransformation studies and sorption
      isotherms of the beta blockers were performed with two natural river sediments
      ("Burgen", "Dausenau") differing in organic carbon content and particle size
      distribution. Biotransformation of beta blockers in the surface water-sediment
      systems exhibited a low to high persistence with 90% disappearance (DT(90))
      ranging from 0.4-10 d (pindolol, atenolol) to >100 d (sotalol, propranolol or
      celiprolol). For sorption studies neither NaN(3) addition nor autoclavation led
      to a complete mass balance of the beta blockers, probably due to
      biotransformation. Isotherms at 6 h (apparent equilibrium, measuring aqueous and
      sediment phase) fitted by the Freundlich equation show that sorption of all beta
      blockers to the Burgen sediment were linear or close to it (i.e., n-values
      between 0.93 and 1.13), while in the Dausenau sediment the sorptions were
      slightly non linear (i.e., n-values 0.77-0.91). In river water the sorbed
      fraction is negligible in comparison to the dissolved fraction. Nevertheless,
      beta blockers can be detected with concentrations up to 86 ng/g (bisoprolol) in
      sediments of small streams containing more than 50% treated wastewater.

PMID- 20030339
TI  - Coadsorption of ciprofloxacin and Cu(II) on montmorillonite and kaolinite as
      affected by solution pH.
AB  - The coadsorption of ciprofloxacin (Cip) and Cu(II) on montmorillonite and
      kaolinite was studied between pH 4.0 and 9.5. At pH < 5.0, Cu(2+), Cip(+) and
      [Cu(II)(Cip(+/-))](2+) were the main species in solution. Between pH 5.0-7.0
      [Cu(II)(Cip(+/-))](2+) was the dominant complex species. Above pH 8.0
      [Cu(II)(Cip(-))(2)](0) precipitated. The presence of Cu(II) exerted no effect on
      the Cip sorption onto montmorillonite at low pH, whereas it increased Cip
      sorption on montmorillonite at pH > 6.0 due to the stronger affinity of Cip
      Cu(II) complexes compared to sole Cip(-) or Cip(+/-), or Cip sorption via a
      Cu(II) bridge increased. In contrast, Cip increased Cu(II) adsorption on
      montmorillonite at pH < 7.0, whereas it decreased the adsorption of Cu(II) on
      kaolinite at pH 6.0-8.0. Cip was sorbed onto the kaolinite surface via
      interaction of carboxyl groups over the entire pH range. At pH 4.0-4.7, Cip(+)
      sorption onto kaolinite's positively charged surface was more favorable than
      sorption of Cip-Cu(II) complexes. Batch experiments and FTIR analyses indicated
      that the coordination between Cip(+/-), Cip(-) and Cu(II) were most likely
      present on kaolinite surface at pH 7.0. At pH > 8.0, Cu(OH)(2) (s) and
      [Cu(II)(Cip(-))(2)](0) precipitated out of solution or on the montmorillonite or
      kaolinite surface, which was not considered evidence for either the sorption of
      Cip or the adsorption of Cu(II).

PMID- 20030340
TI  - Time-resolved loading of monomers into bilayers with different curvature.
AB  - Directed assembly of nanostructures within temporary and recyclable self
      assembled scaffolds is emerging as an attractive method for the synthesis of
      nanomaterials with programmed properties. Understanding interactions of building
      blocks with amphiphilic scaffolds is critical for rational design of new
      nanostructures and nanodevices. Here we examine loading of hydrophobic monomers
      into bilayers with different curvatures. Time-resolved loading was studied by
      high performance liquid chromatography and dynamic light scattering. Despite
      differences in initial bilayer geometry, loading rates and maximum bilayer
      capacity are the same for liposomes with radii ranging from 25 to 100 nm. When
      using divinylbenzene (DVB) and dimyristoylphosphatidylcholine (DMPC),
      monomer/lipid loading ratio of 1.2 was achieved within 12 h. While accommodation
      of a large amount of monomers is likely to be accompanied with significant
      changes in bilayer structure, all liposomes in this study including those with
      smallest size and higher bilayer curvature retain encapsulated content and show
      no evidence of fusion during monomer loading. These results contribute to our
      understanding of interactions between hydrophobic molecules and lipid bilayers
      and expand the scope of the directed assembly method.

PMID- 20030341
TI  - Synthesis, monolayer formation, characterization, and nanometer-scale
      photolithographic patterning of conjugated oligomers bearing terminal
      thioacetates.
AB  - The synthesis of alpha-thioacetate terminated quaterthiophene and phenylene
      thiophene materials, possessing thioacetate, oxetane, and alkyl groups at their
      omega-termini, is described. After deprotection these molecules were adsorbed
      onto Au films and the resulting self-assembled monolayers were characterized by X
      ray photoelectron spectroscopy (XPS) and friction force microscopy (FFM). FFM
      indicated that monolayers formed by the dithioacetates had the highest
      coefficients of friction, followed by the oxetane-terminated adsorbates, with the
      alkyl-functionalized materials showing the lowest friction coefficients. These
      data may be understood in terms of differences in molecular packing. The
      quaterthiophene adsorbates also yielded higher friction coefficients than their
      phenylene-thiophene counterparts. Micrometer-scale patterns were fabricated by
      mask-based exposure to 244 nm light, and characterized by FFM. Nanometer-scale
      patterns were fabricated using near-field exposure and characterized by FFM. The
      images obtained demonstrated that features of conjugated oligomers with high
      spatial resolution (59 nm, ca. lambda/4) were achievable.

PMID- 20030342
TI  - Quantitation of (beta)N-Alkanoyl-5-hydroxytryptamides in coffee by means of LC
      MS/MS-SIDA and assessment of their gastric acid secretion potential using the HGT
      1 cell assay.
AB  - A straightforward stable isotope dilution analysis (SIDA) for the reliable
      quantitative determination of (beta)N-C(18:0)- to (beta)N-C(24:0)-alkanoyl-5
      hydroxytryptamides (C5HTs) in coffee powder and beverages by means of LC-MS/MS
      was developed. The developed SIDA showing accuracy values of 92.6-107% and
      precision between 0.5 and 7% relative standard deviation for the individual
      derivatives allowed the sensitive and selective quantification of the target
      compounds in coffee beverages. Depending on the type of coffee, quantitation
      revealed C5HT levels between 65 and 144 microg/L in filtered coffee and up to
      3500 microg/L in a French press beverage, thus indicating that about 0.3 or 7.2%
      of the C5HTs were extracted from the coffee powder into the beverage when using
      the cellulose filter method or the French press, respectively. To estimate the
      potential contribution of the C5HTs to the phenomenon of stomach irritation after
      ingestion of coffee brew, in vitro cell studies were performed with pure
      individual 5-hydroxytryptamides and a mixture of the predominating derivatives in
      ratios matching those found in coffee. All substances tested induced a decrease
      in the intracellular proton index (IPX) coined as an indicator of stomach acid
      secretion. While the biomimetic C5HT mixture was highest in its inducing effect,
      the individual stearic acid, oleic acid, and linoleic acid 5-hydroxytryptamide
      did not differ significantly from each other, but showed a less pronounced effect
      compared to arachinic acid 5-hydroxytryptamide. In conclusion, not the grade of
      saturation seems to determine the C5HT's mode of action in driving the stomach
      acid secretion, rather than the fatty acid chain length.

PMID- 20030343
TI  - Novel 3-arylideneindolin-2-ones as inhibitors of NAD+ -dependent histone
      deacetylases (sirtuins).
AB  - Class III histone deacetylases (sirtuins) play pivotal roles in many cellular
      processes. They are linked to extended lifespan and to the pathogenesis of cancer
      and neuronal disorders. We present novel sirtuin inhibitors based on a 6,7
      dichloro-2-oxindole scaffold with low micromolar activity. In vitro activity was
      rationalized by docking studies, and hyperacetylation of sirtuin targets could be
      demonstrated in cell culture.

PMID- 20030344
TI  - Structure and total synthesis of fungal calpinactam, a new antimycobacterial
      agent.
AB  - A new fungal metabolite designated calpinactam (1) was isolated from the culture
      broth of Mortierella alpina FKI-4905, and its structure was elucidated by
      spectroscopic analyses including NMR experiments. Calpinactam was found to be a
      hexapeptide with a caprolactam ring at its C-terminal. Its absolute
      stereochemistry was determined by amino acid analysis and total synthesis.
      Calpinactam selectively inhibited the growth of mycobacteria among various
      microorganisms. The MIC values of calpinactam against Mycobacterium smegmatis and
      M. tuberculosis were 0.78 and 12.5 microg/mL, respectively.

PMID- 20030345
TI  - Water-controlled regioselectivity of Pd-catalyzed domino reaction involving a C-H
      activation process: rapid synthesis of diverse carbo- and heterocyclic skeletons.
AB  - A palladium-catalyzed domino reaction involving a C-H activation process to
      synthesize diverse carbo- and heterocyclic skeletons was developed. H(2)O (as
      cosolvent) is used to control the regioselectivity.

PMID- 20030346
TI  - Nonaqueous photorheological fluids based on light-responsive reverse wormlike
      micelles.
AB  - Fluids whose flow properties can be altered by light are an emerging class of
      functional materials, with potential applications in microscale actuators and
      valves. While many such photorheological (PR) fluids have been developed over the
      years, most are based on specialized organized molecules that require synthesis.
      We have instead sought to develop PR fluids using inexpensive chemical components
      that are commercially available, and this approach has been successfully applied
      to aqueous systems. Here, we demonstrate a simple class of nonaqueous PR fluids
      based on the phospholipid, lecithin, and the organic derivative, para-coumaric
      acid (PCA). The combination of lecithin with the trans form of PCA results in
      reverse wormlike micelles, which are long, flexible chains that undergo
      entanglement, thereby giving rise to viscoelastic fluids. Upon UV irradiation,
      trans-PCA is photoisomerized to its cis form, which has a lower polarity and
      hydrogen-bonding tendency. This causes a significant reduction in the length of
      the micellar chains, and in turn, the fluid viscosity drops more than 1000-fold.
      We show that photoresponsive reverse micelles can be formed in a range of organic
      solvents including cyclohexane, n-alkanes, alkenes, and fatty acid esters.

PMID- 20030347
TI  - Autonomous motion of vesicle via ion exchange.
AB  - The autonomous motion of vesicle is observed in a simple chemical system. A
      vesicle composed of didodecyldimethylammonium bromide DDAB breaks down by ion
      exchange from Br(-) to I(-). When an electrolyte is supplied to vesicles, some of
      them begin to move after an induction period. They continue to move, leaving
      behind the reaction products on the trail. The ion exchange decreases the vesicle
      size, and smaller vesicles remain after the motion. We examine the
      characteristics of this motion. The surface tension of the DDAB-containing
      aqueous phase depends on the KI concentration. Considering this result carefully,
      we conclude that vesicles can move when the ion exchange from Br(-) to I(-)
      proceeds irreversibly. Then, inhomogeneity in the vesicle membrane develops
      because of the coagulating nature of the product, didodecyldimethylammonium
      iodide (DDAI), which is sparingly soluble in water. Inhomogeneous properties of
      vesicle membranes are then generated, which induce surface transport of the
      reaction product and flow in the water pool. As a result, a couple of convection
      rolls appear in the water pool of the vesicle. The convection rolls drive vesicle
      motion. A simple model for the semiquantitative description is proposed.

PMID- 20030348
TI  - Ultralyophobic oxidized aluminum surfaces exhibiting negligible contact angle
      hysteresis.
AB  - Ultralyophobic oxidized aluminum surfaces exhibiting negligible contact angle
      hysteresis for probe liquids were prepared by chemical vapor deposition (CVD) of
      bis((tridecafluoro-1,1,2,2,-tetrahydrooctyl)-dimethylsiloxy)methylsilane
      (CF(3)(CF(2))(5)CH(2)CH(2)Si(CH(3))(2)O)(2)SiCH(3)H, (R(F)Si(Me)(2)O)(2)SiMeH).
      Oxidized aluminum surfaces were prepared by photooxidation/cleaning of sputter
      coated aluminum on silicon wafers (Si/Al(Al(2)(O(3)))) using oxygen plasma. X-ray
      photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) confirmed that
      this facile CVD method produces a monolayer with a thickness of 1.1 nm on the
      Si/Al(Al(2)(O(3))) surface without a discernible change in surface morphology.
      After monolayer deposition, the hydrophilic Si/Al(Al(2)(O(3))) surface became
      both hydrophobic and oleophobic and exhibited essentially no contact angle
      hysteresis for water and n-hexadecane (advancing/receding contact angles
      (theta(A)/theta(R)) = 110 degrees/109 degrees and 52 degrees/50 degrees,
      respectively). Droplets move very easily on this surface and roll off of slightly
      tilted surfaces, independently of the contact angle (which is a practical
      definition of ultralyophobic). A conventional fluoroalkylsilane monolayer was
      also prepared from 1H,1H,2H,2H-perfluorodecyltrimethoxysilane
      (CF(3)(CF(2))(7)CH(2)CH(2)Si(OCH(3))(3), R(F)Si(OMe)(3)) for comparison. The
      theta(A)/theta(R) values for water and n-hexadecane are 121 degrees/106 degrees
      and 76 degrees/71 degrees, respectively. The larger hysteresis values indicate
      the "pinning" of probe liquids, even though advancing contact angles are larger
      than those of the (R(F)Si(Me)(2)O)(2)SiMeH-derived monolayers. The
      (R(F)Si(Me)(2)O)(2)SiMeH-derived monolayers have excellent hydrolytic stability
      in water. We propose that the (R(F)Si(Me)(2)O)(2)SiMeH-derived monolayers are
      flexible and liquidlike and that drops in contact with these surfaces experience
      very low energy barriers between metastable states, leading to the formation of
      nonhysteretic ultralyophobic surfaces.

PMID- 20030349
TI  - Solvent-controlled 2D host-guest (2,7,12-trihexyloxytruxene/coronene) molecular
      nanostructures at organic liquid/solid interface investigated by scanning
      tunneling microscopy.
AB  - The two-dimensional (2D) self-assembled networks of 2,7,12-trihexyloxytruxene
      (Tr) are shown to accommodate coronene guest molecules on highly oriented
      pyrolytic graphite (HOPG) surfaces. The host-guest structures are revealed by
      scanning tunneling microscopy (STM) at liquid/solid interfaces. The effect of
      solvents on the host-guest structures is intensively investigated in different
      solvents such as 1,2,4-trichlorobenzene (TCB), 1-phenyloctane, 1-octanol, and
      tetradecane. In contrast to the similar 2D hexagonal self-assembly of Tr host
      template on HOPG in different solvents, the formation of host-guest
      nanostructures of coronene in Tr 2D network strongly depend on the polarity of
      the solvents. The thermodynamic equilibrium during the host-guest assembly
      process is discussed, and the solvent-guest interaction is proposed as a main
      contributor for the observed solvent effect in the 2D host-guest self-assembly
      process. The results are significant to surface host-guest chemistry and
      nanopatterning.

PMID- 20030350
TI  - Combined role of water and surface chemistry in reactive adsorption of ammonia on
      graphite oxides.
AB  - Graphite oxide synthesized using the Brodie method was tested for ammonia
      adsorption after two different levels of drying in dynamic conditions at the
      ambient temperature. Surface characterization before and after exposure to
      ammonia was done using X-ray diffraction (XRD), Fourier transform infrared (FTIR)
      spectroscopy, and potentiometric titration. On the surface of the initial
      materials, besides epoxy, hydroxyl, and carboxylic groups, various amounts of
      water within the interlayer space are present. The results showed that ammonia is
      intercalated within the interlayer space of graphite oxides. Water enhances the
      amount of ammonia adsorbed via the dissolution and promotes the dissociation of
      surface functional groups. This enhances formation of ammonium ions. On the other
      hand, water screens the accessibility of epoxy and -COOH groups for reactions
      with ammonia and thus limits the amount adsorbed. The retention of ammonia on a
      partially dried graphite oxide is enhanced not only owing to those reactions but
      also because of the formation of new adsorption centers as a result of an
      incorporation of ammonia to the graphene layers.

PMID- 20030351
TI  - Glucose-based fluorescent low-molecular mass compounds: creation of simple and
      versatile supramolecular gelators.
AB  - Five novel glucose-based naphthalene derivatives with linkers containing
      hydrazine, ethylenediamine, 1,3-propanediamine, 1,4-butanediamine, and 1,6
      hexanediamine, respectively (1, 2, 3, 4, and 5) were designed and prepared. The
      gelation test revealed the following points: (1) within the 30 solvents tested, 1
      gels water only; (2) in contrast, 2 gels not only water, but also 11 of the
      organic solvents tested, a typical "ambidextrous gelator"; (3) 3, 4, and 5,
      however, gel organic solvents only, and the numbers of solvents gelled are 11, 11
      and 13, respectively. Clearly, these compounds are effective low-molecular mass
      gelators, and show transitions from a low-molecular mass hydrogelator to an
      ambidextrous gelator and then to low-molecular mass organogelators with a slight
      increase in the length of the spacers. Interestingly, 5 is a super gelator to
      acetonitrile, of which the minimum gelation concentration is only 0.07%, w/v. The
      morphology, microstructure and molecular aggregation of the system strongly
      depend on the transition, as revealed by SEM, contact angle, energy dispersive X
      ray spectroscopy, and XRD measurements. More interestingly, an aggregation
      induced enhanced emission was observed along with gelation. Furthermore, the
      system appeared as a supramolecular chiroptical switch in the sol-gel process
      that is the chirality disappeared when the gel was heated to solution, whereas it
      reappeared when cooled to a gel.

PMID- 20030352
TI  - Compact and versatile nickel-nitrilotriacetate-modified quantum dots for protein
      imaging and Forster resonance energy transfer based assay.
AB  - The generation of compact quantum dots (QDs) probes is of critical importance for
      visualizing molecular interaction occurring in biological context, particularly
      when using the Forster resonance energy transfer (FRET) approach. This Article
      reports novel water-soluble compact CdSe/ZnS QDs prepared by ligand exchange
      reaction using thiolated nitrilotriacetate (NTA). The resulting NTA-QDs revealed
      higher stability and remarkable conjugation efficiency compared to the other QDs
      prepared with different ligands by using the ligand exchange method. The Ni-NTA
      group is a well-known binding moiety for the detection and purification of
      oligohistidine-tagged recombinant proteins. We demonstrated that NiNTA-QDs
      prepared by Ni(2+) complexation exhibited highly specific binding ability toward
      6-histidine (His)-tagged peptides present in various experimental conditions
      (buffer solution, agarose beads, and HEK cells). Importantly, the compact NiNTA
      QDs serve as an efficient FRET donor. These results suggest that the stable and
      highly selective multifunctional NTA-QDs can be useful for labeling and tracking
      molecular interactions within biological context.

PMID- 20030353
TI  - Computational study for water sorption in AlPO(4)-5 and AlPO(4)-11 molecular
      sieves.
AB  - The unusual water adsorption behavior in aluminophosphate molecular sieves
      AlPO(4)-5 and AlPO(4)-11 was studied using canonical Monte Carlo and periodic
      density functional theory (DFT) calculation. The number of adsorbed water
      molecules per cavity ranging from 1 to 12 were located inside the molecular
      sieves by canonical Monte Carlo simulation methods using a "compass" forcefield.
      The DFT calculations were done for optimizing each structure with and without
      adsorbed water molecules employing generalized gradient approximation with the
      Perdew-Burke-Ernzerhof exchange-correction functional. Both classical and quantum
      mechanical calculations have exhibited hydrogen bonding between adsorbed water
      molecules inside the main 12-membered ring. The Al-O-P angles were observed to
      decrease after adsorbing water molecules in geometry optimized AlPO(4)-5 and
      AlPO(4)-11 molecular sieves. DFT calculations illustrate that the initial loading
      of water in the large cavity is due to the mild acidity in the framework but the
      isobaric increase in loading is due to the abundant hydrogen bonding between
      adsorbed water at higher water loading.

PMID- 20030354
TI  - Synthesis and photocatalytic properties of mixed polyoxometalate-porphyrin
      copolymers obtained from Anderson-type polyoxomolybdates.
AB  - Hybrid polyoxometalate-porphyrin copolymeric films are obtained by the electro
      oxidation of zinc octaethylporphyrin (ZnOEP) and zinc 5,15-dipyridinium
      octaethylporphyrin (5,15-ZnOEP(py)(2)(2+)) in the presence of the polyoxometalate
      [MnMo(6)O(18){(OCH(2))(3)CNHCO(4-C(5)H(4)N)}(2)](3-) (Py-POM-Py). These films
      allow the photocatalytic reduction of Ag(I)(2)SO(4) under visible irradiation in
      air in the presence of propan-2-ol at the 2D interface between water and the
      copolymeric films. The formation of metallic Ag(0) nanowires and triangular
      nanosheets is observed.

PMID- 20030355
TI  - Photoinduced formation of shape-selective Pt nanoparticles.
AB  - A new synthetic route has been utilized for the formation of multiple-shaped Pt
      nanoparticles (NPs) under UV-photoirradiation. The one-step process exclusively
      generates different shapes, such as spheres, cubes, short and long wires, and
      flakelike nanostructures. The reduction of Pt(IV) ions was done using alkaline
      2,7-DHN in CTAB micellar media under 3 h UV-photoirradiation. The synthesized Pt
      NPs are stable for more than 4 months in ambient conditions. By changing the
      surfactant-to-metal ion molar ratios and the concentration of reducing agent, the
      particle size and shape can be tuned. The mechanisms of the particles formation
      with variable shapes and the effects of different reaction parameters are studied
      in detail. The present approach can be extended to a fast synthetic method for
      the formation of other metallic and semiconductor particles with variable shapes.
      The evolved Pt NPs will find promising applications in different types of organic
      and inorganic catalysis reactions, medicinal applications, and nanoelectronics.

PMID- 20030356
TI  - Alkyne [3 + 2] cycloadditions of iodosydnones toward functionalized 1,3,5
      trisubstituted pyrazoles.
AB  - The cycloaddition of 4-iodosydnones with terminal alkynes proceeds with excellent
      regiocontrol to provide 5-iodo pyrazoles. These products participate smoothly in
      subsequent C-C and C-heteroatom bond forming processes.

PMID- 20030357
TI  - Orientation-dependent plasticity in metal nanowires under torsion: twist boundary
      formation and Eshelby twist.
AB  - We show that the plastic deformation of nanowires under torsion can be either
      homogeneous or heterogeneous, regardless of size, depending on the wire
      orientation. Homogeneous deformation occurs when 110-oriented face-centered-cubic
      metal wires are twisted, leading to the nucleation of coaxial dislocations,
      analogous to the Eshelby twist mechanism. Heterogeneous deformation is predicted
      for 111 and 100 wires under torsion, localized at the twist boundaries. These
      simulations also reveal the detailed mechanisms of twist boundary formation from
      dislocation reactions.

PMID- 20030358
TI  - Whole genome expression analysis reveals differential effects of TiO2 nanotubes
      on vascular cells.
AB  - The response of primary human endothelial (ECs) and vascular smooth muscle cells
      (VSMCs) to TiO2 nanotube arrays is studied through gene expression analysis.
      Microarrays revealed that nanotubes enhanced EC proliferation and motility,
      decreased VSMC proliferation, and decreased expression of molecules involved in
      inflammation and coagulation in both cell types. Networks generated from
      significantly affected genes suggest that cells may be sensing nanotopographical
      cues via pathways previously implicated in sensing shear stress.

PMID- 20030359
TI  - Design of bis-spiropyran ligands as dipolar molecule receptors and application to
      in vivo glutathione fluorescent probes.
AB  - Despite considerable efforts toward the development of various sophisticated
      spiropyrans for metal ion sensing, less attention has been paid to organic
      molecule sensing. One of the major difficulties for detection of organic
      molecules using a spiropyran is the weak and nonspecific interaction between the
      spiropyran and the target. Here, we report the synthesis and molecular
      recognition characterization of two bis-spiropyrans for dipolar molecules and
      their application to in vivo glutathione (GSH) fluorescent probes. Unlike the
      mono-spiropyrans, the newly designed bis-spiropyran molecules feature a rigidly
      maintained molecular cleft and two spiropyran units as binding modules. The
      molecular recognition is based on multipoint electrostatic interactions and
      structure complementarity between the opened merocyanine form of the spiropyran
      and the analyte. It was observed that the spiropyran 1a binds GSH in aqueous
      solution with high affinity (K = (7.52 +/- 1.83) x 10(4) M(-1)) and shows strong
      fluorescence emission upon binding. Remarkably, fluorescence output of 1a is not
      significantly affected by other amino acids and peptides, especially,
      structurally similar compounds, such as cysteine and homocysteine. Furthermore,
      fluorescence anisotropy and confocal fluorescent microscopy confirmed that
      spiropyran 1a is a comparatively good candidate for intracellular delivery and
      can be accumulated intensively into cells. Thus, 1a can be utilized in vivo as a
      GSH probe or as a marker to show the level of intracellular GSH.

PMID- 20030360
TI  - Rapid nanoimprinting and excellent piezoresponse of polymeric ferroelectric
      nanostructures.
AB  - Nanostructured ferroelectric patterns are promising for a wide range of
      applications, including sensing and actuation, data storage, photonics,
      spintronics, and energy conversion and storage. In this work, a rapid
      nanoimprinting technique is developed to pattern ferroelectric poly(vinylidene
      fluoride-trifluoroethylene) [P(VDF-TrFE)] copolymers in just 3 min, which exhibit
      excellent ferroelectricity and piezoresponse without any post-imprinting
      annealing. The effects of imprinting conditions have been thoroughly
      investigated, and the optimal imprinting parameters for excellent pattern
      transfer have been identified. The application of the imprinted polymeric
      patterns as a ferroelectric nonvolatile memory for data storage has also been
      demonstrated and discussed.

PMID- 20030361
TI  - Palladium-catalyzed gamma-selective and stereospecific allyl-aryl coupling
      between acyclic allylic esters and arylboronic acids.
AB  - Reactions between acyclic (E)-allylic acetates and arylboronic acids in the
      presence of a palladium catalyst prepared from Pd(OAc)(2), phenanthroline (or
      bipyridine), and AgSbF(6) (1:1.2:1) proceeded with excellent gamma-selectivity to
      afford allyl-aryl coupling products with E-configuration. The reactions of alpha
      chiral allylic acetates took place with excellent alpha-to-gamma chirality
      transfer with syn stereochemistry to give allylated arenes with a stereogenic
      center at the benzylic position. The reaction tolerated a broad range of
      functional groups in both the allylic acetates and the arylboronic acids.
      Furthermore, gamma-arylation of cinnamyl alcohol derivatives afforded gem
      diarylalkane derivatives containing an unconjugated alkenic substituent. The
      synthetic utility of this method was demonstrated by its utilization in an
      efficient synthesis of (+)-sertraline, an antidepressant agent. The observed
      gamma-regioselectivity and E-1,3-syn stereochemistry were rationalized based on a
      Pd(II) mechanism involving transmetalation between a cationic
      mono(acyloxo)palladium(II) complex and arylboronic acid, and directed
      carbopalladation followed by syn-beta-acyloxy elimination. The results of
      stoichiometric reactions of palladium complexes related to possible intermediates
      were fully consistent with the proposed mechanism.

PMID- 20030362
TI  - Versatile solution phase triangular silver nanoplates for highly sensitive
      plasmon resonance sensing.
AB  - Solution phase triangular silver nanoplates (TSNP) with versatile tunability
      throughout the visible-NIR wavelengths are presented as highly sensitive
      localized surface plasmon refractive index sensors. A range of 20 TSNP solutions
      with edge lengths ranging from 11 to 200 nm and aspect ratios from 2 to 13 have
      been studied comprehensively using AFM, TEM, and UV-vis-NIR spectroscopy. Studies
      of the localized surface plasmon resonance (LSPR) peak's sensitivity to
      refractive index changes are performed using a simple sucrose concentration
      method whereby the surrounding refractive index can solely be changed without
      variation in any other parameter. The dependence of the TSNP localized surface
      plasmon resonance (LSPR) peak wavelength lambda(max) and its bulk refractive
      index sensitivity on the nanoplate's structure is determined. LSPR sensitivities
      are observed to increase linearly with lambda(max) up to 800 nm, with the values
      lying within the upper limit theoretically predicted for optimal sensitivity,
      notwithstanding any diminution due to ensemble averaging. A nonlinear increase in
      sensitivity is apparent at wavelengths within the NIR region with values reaching
      1096 nm.RIU(-1) at lambda(max) 1093 nm. Theoretical studies performed using a
      simple aspect ratio dependent approximation method and discrete dipole
      approximation methods confirm the dependence of the LSPR bulk refractive index
      sensitivity upon the TSNP aspect ratio measured experimentally. These studies
      highlight the importance of this key parameter in acquiring such high
      sensitivities and promote these TSNP sols for sensing applications at appropriate
      wavelengths for biological samples.

PMID- 20030363
TI  - Sex-related differences in alkaloid chemical defenses of the dendrobatid frog
      Oophaga pumilio from Cayo Nancy, Bocas del Toro, Panama.
AB  - Poison frogs contain an alkaloid-based chemical defense that is sequestered
      directly from a diet of alkaloid-containing arthropods. Geographic and temporal
      variation in alkaloid defense is common in poison frogs and is generally
      attributed to differences in the availability of alkaloid-containing arthropods.
      Variable chemical defense in poison frogs may have important consequences for
      predator-prey interactions, requiring a full understanding of the factors
      involved in explaining such variation. In the present study, we examine alkaloid
      variation in the dendrobatid poison frog Oophaga pumilio between males and
      females on Cayo Nancy (Isla Solarte), located in the Bocas del Toro archipelago
      of Panama. On average, females contained a significantly larger number and
      quantity of alkaloids when compared to males. Alkaloid composition varied
      significantly between males and females, illustrating that chemical defense in
      this population of O. pumilio is sex-dependent. The variation in alkaloids
      between sexes is attributed to differences in feeding and behavior between males
      and females. The majority of alkaloids present in the skin of O. pumilio appear
      to be of oribatid mite origin, supporting the importance of these dietary
      arthropods in the chemical defense of poison frogs.

PMID- 20030364
TI  - Assessing pressurized liquid extraction for the high-throughput extraction of
      marine-sponge-derived natural products.
AB  - In order to compare the utility of standard solvent partitioning (SSP) versus
      accelerated solvent extraction (ASE), a series of experiments were performed and
      evaluated. Overall yields, solvent consumption, processing time, and chemical
      stability of the fractions obtained by both methods were compared. Five marine
      sponges were selected for processing and analysis containing 12 structurally
      distinct, bioactive natural products. Extracts generated using SSP and ASE were
      assessed for chemical degradation using comparative LC MS-ELSD. The extraction
      efficiency (EE) of the ASE apparatus was 3 times greater than the SSP method on
      average, while the total extraction yields (TEY) were roughly equivalent.
      Furthermore, the ASE methodology required only 2 h to process each sample versus
      80 h for SSP, and the LC MS-ELSD from extracts of both methods appeared
      comparable. These results demonstrate that ASE can serve as an effective high
      throughput methodology for extracting marine organisms to streamline the
      discovery of novel and bioactive natural products.

PMID- 20030365
TI  - Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with
      antileishmanial activity.
AB  - Tropical parasitic and infectious diseases, such as leishmaniasis, pose enormous
      global health threats, but are largely neglected in commercial drug discovery
      programs. However, the Panama International Cooperative Biodiversity Group (ICBG)
      has been working to identify novel treatments for malaria, Chagas' disease, and
      leishmaniasis through an investigation of plants and microorganisms from Panama.
      We have pursued activity-guided isolation from an extract of Lyngbya majuscula
      that was found to be active against leishmaniasis. A new modified linear peptide
      from the dragonamide series was isolated, dragonamide E (1), along with two known
      modified linear peptides, dragonamide A (2) and herbamide B (3). Dragonamides A
      and E and herbamide B exhibited antileishmanial activity with IC50 values of 6.5,
      5.1, and 5.9 microM, respectively. Spectroscopic and stereochemical data for
      dragonamide E (1) and herbamide B (3; the spectroscopic and stereochemical data
      for this substance is incomplete in the literature) are presented as well as
      comparisons of biological activity within the dragonamide compound family.
      Biosynthetic differences among marine compounds with a terminal free amide are
      also discussed.

PMID- 20030366
TI  - Decoding of lipoprotein-receptor interactions: properties of ligand binding
      modules governing interactions with apolipoprotein E.
AB  - Clusters of complement-type ligand binding repeats in the LDL receptor family are
      thought to mediate the interactions between these receptors and their various
      ligands. Apolipoprotein E, a key ligand for cholesterol homeostasis, has been
      shown to interact with LDLR, LRP, and VLDLR, through these clusters. LDLR and
      VLDLR each contain a single ligand binding repeat cluster, whereas LRP contains
      three large clusters of ligand binding repeats, each with ligand binding
      functions. We show that within sLRP3 the three-repeat subcluster CR16-18
      recapitulated ligand binding to the isolated receptor binding portion of ApoE
      (residues 130-149). Binding experiments with LA3-5 of LDLR and CR16-18 showed
      that a conserved W25/D30 pair appears to be critical for high-affinity binding to
      ApoE(130-149). The triple repeat LA3-5 showed the expected interaction with
      ApoE(1-191).DMPC, but surprisingly CR16-18 did not interact with this form of
      ApoE. To understand these differences in ApoE binding affinity, we introduced
      mutations of conserved residues from LA5 into CR18 and produced a CR16-18 variant
      capable of binding ApoE(1-191).DMPC. This change cannot fully be accounted for by
      the interaction with the proposed ApoE receptor binding region; therefore, we
      speculate that LA5 is recognizing a distinct epitope on ApoE that may only exist
      in the lipid-bound form. The combination of avidity effects with this distinct
      recognition process likely governs the ApoE-LDL receptor interaction.

PMID- 20030367
TI  - High-tech charcoal fights climate change.

PMID- 20030369
TI  - Theoretical study on acidities of (S)-proline amide derivatives in DMSO and its
      implications for organocatalysis.
AB  - The acidities (pK(a) values) of proline amide derivatives are of great importance
      for understanding the catalytic activity of proline-based organocatalysts. The
      development of new catalysts could also benefit from the systematic study of the
      pK(a) values of these compounds. However, only a few pK(a) values of the proline
      based organocatalysts are currently available due to the difficulty in
      experimentally measurements. In this work, we set out to study the pK(a) values
      of various proline amide derivatives with theoretical calculations. Different
      theoretical methods were evaluated and the combined method, B3PW91/6
      311++G(3df,2p)//B3LYP/6-31+G(d)//HF//CPCM/UA0, was found to be the best one in
      reproducing the pK(a) values of structurally unrelated amides and amide
      derivatives in DMSO. The MAD and RMSE of the newly developed theoretical model
      equal to 0.98 and 1.3 pK units, respectively. The method also enabled the
      systematically study on various structural effects on pK(a) values of proline
      amide derivatives, such as the ZE-isomerization, remote substitution, and alpha
      substitution effects, for the first time. The pK(a) values of a series of chiral
      amides were also studied in this work. Finally, we applied the theoretical method
      to predict a large number of proline-based organocatalysts and established an
      extensive acidity scale of the compounds.

PMID- 20030368
TI  - Life cycle assessment of biochar systems: estimating the energetic, economic, and
      climate change potential.
AB  - Biomass pyrolysis with biochar returned to soil is a possible strategy for
      climate change mitigation and reducing fossil fuel consumption. Pyrolysis with
      biochar applied to soils results in four coproducts: long-term carbon (C)
      sequestration from stable C in the biochar, renewable energy generation, biochar
      as a soil amendment, and biomass waste management. Life cycle assessment was used
      to estimate the energy and climate change impacts and the economics of biochar
      systems. The feedstocks analyzed represent agricultural residues (corn stover),
      yard waste, and switchgrass energy crops. The net energy of the system is
      greatest with switchgrass (4899 MJ t(-1) dry feedstock). The net greenhouse gas
      (GHG) emissions for both stover and yard waste are negative, at -864 and -885 kg
      CO(2) equivalent (CO(2)e) emissions reductions per tonne dry feedstock,
      respectively. Of these total reductions, 62-66% are realized from C sequestration
      in the biochar. The switchgrass biochar-pyrolysis system can be a net GHG emitter
      (+36 kg CO(2)e t(-1) dry feedstock), depending on the accounting method for
      indirect land-use change impacts. The economic viability of the pyrolysis-biochar
      system is largely dependent on the costs of feedstock production, pyrolysis, and
      the value of C offsets. Biomass sources that have a need for waste management
      such as yard waste have the highest potential for economic profitability (+$69 t(
      1) dry feedstock when CO(2)e emission reductions are valued at $80 t(-1) CO(2)e).
      The transportation distance for feedstock creates a significant hurdle to the
      economic profitability of biochar-pyrolysis systems. Biochar may at present only
      deliver climate change mitigation benefits and be financially viable as a
      distributed system using waste biomass.

PMID- 20030370
TI  - Reductive coupling of nitrogen monoxide (*NO) facilitated by heme/copper
      complexes.
AB  - The interactions of nitrogen monoxide (*NO; nitric oxide) with transition metal
      centers continue to be of great interest, in part due to their importance in
      biochemical processes. Here, we describe *NO((g)) reductive coupling chemistry of
      possible relevance to that process (i.e., nitric oxide reductase (NOR)
      biochemistry), which occurs at the heme/Cu active site of cytochrome c oxidases
      (CcOs). In this report, heme/Cu/*NO((g)) activity is studied using 1:1 ratios of
      heme and copper complex components, (F(8))Fe (F(8) = tetrakis(2,6
      difluorophenyl)porphyrinate(2-)) and [(tmpa)Cu(I)(MeCN)](+) (TMPA = tris(2
      pyridylmethyl)amine). The starting point for heme chemistry is the mononitrosyl
      complex (F(8))Fe(NO) (lambda(max) = 399 (Soret), 541 nm in acetone). Variable
      temperature (1)H and (2)H NMR spectra reveal a broad peak at delta = 6.05 ppm
      (pyrrole) at room temperature (RT), which gives rise to asymmetrically split
      pyrrole peaks at 9.12 and 8.54 ppm at -80 degrees C. A new heme dinitrosyl
      species, (F(8))Fe(NO)(2), obtained by bubbling (F(8))Fe(NO) with *NO((g)) at -80
      degrees C, could be reversibly formed, as monitored by UV-vis (lambda(max) = 426
      (Soret), 538 nm in acetone), EPR (silent), and NMR spectroscopies; that is, the
      mono-NO complex was regenerated upon warming to RT. (F(8))Fe(NO)(2) reacts with
      [(tmpa)Cu(I)(MeCN)](+) and 2 equiv of acid to give [(F(8))Fe(III)](+),
      [(tmpa)Cu(II)(solvent)](2+), and N(2)O((g)), fitting the stoichiometric *NO((g))
      reductive coupling reaction: 2*NO((g)) + Fe(II) + Cu(I) + 2H(+) --> N(2)O((g)) +
      Fe(III) + Cu(II) + H(2)O, equivalent to one enzyme turnover. Control reaction
      chemistry shows that both iron and copper centers are required for the NOR-type
      chemistry observed and that, if acid is not present, half the *NO is trapped as a
      (F(8))Fe(NO) complex, while the remaining nitrogen monoxide undergoes copper
      complex promoted disproportionation chemistry. As part of this study,
      [(F(8))Fe(III)]SbF(6) was synthesized and characterized by X-ray crystallography,
      along with EPR (77 K: g = 5.84 and 6.12 in CH(2)Cl(2) and THF, respectively) and
      variable-temperature NMR spectroscopies. These structural and physical properties
      suggest that at RT this complex consists of an admixture of high and intermediate
      spin states.

PMID- 20030371
TI  - A versatile tripodal amide receptor for the encapsulation of anions or hydrated
      anions via formation of dimeric capsules.
AB  - A bowl-shaped tripodal receptor with an appropriately positioned amide
      functionality on the benzene platform and electron-withdrawing p-nitrophenyl
      terminals (L(1)) has been designed, synthesized, and studied for the anion
      binding properties. The single-crystal X-ray crystallographic analysis on
      crystals of L(1) with tetrabutylammonium salts of nitrate (1), acetate (2),
      fluoride (3), and chloride (4) obtained in moist dioxane medium showed
      encapsulation of two NO(3)(-), [(AcO)(2)(H(2)O)(4)](2-), [F(2)(H(2)O)(6)](2-),
      and [Cl(2)(H(2)O)(4)](2-) respectively as the anionic guests inside the staggered
      dimeric capsular assembly of L(1). The p-nitro substitution in the aryl terminals
      assisted the formation of dimeric capsular assembly of L(1) exclusively upon
      binding/encapsulating above different guests. Though L(1) demonstrates capsule
      formation upon anion or hydrated anion complexation for all of the anions studied
      here, its positional isomer with the o-nitro-substituted tripodal triamide
      receptor L(2) selectively formed the dimeric capsular assembly upon encapsulation
      of [F(2)(H(2)O)(6)](2-) and noncapsular aggregates in the cases of other anions
      such as Cl(-), NO(3)(-), and AcO(-). Interestingly, structural investigations
      upon anion exchange of the complexes revealed that both isomers have selectivity
      toward the formation of a [F(2)(H(2)O)(6)](2-) encapsulated dimeric capsule. In
      contrast, solution-state (1)H NMR titration studies of L(1) and L(2) in DMSO-d(6)
      with AcO(-) indicated 1:3 (host:guest) binding.

PMID- 20030372
TI  - Octahedral copper(II) and tetrahedral copper(I) double-strand helicates: chiral
      self-recognition and redox behavior.
AB  - The racemic form of 5 ((RR)5 + (SS)5) gives dinuclear complexes of 2:2
      stoichiometry both with Cu(II), acting as a bis-terdentate ligand, and with
      Cu(I), acting as a bis-bidentate ligand. Single crystal X-ray diffraction studies
      have shown that the Cu(II) complex exists as double-strand homochiral helicate
      molecules: P,P-[Cu(2)(II)((RR)5)(2)](4+) and M,M-[Cu(2)(II)((SS)5)(2)](4+); in
      which the two trans-1,2-cyclohexanediamine subunits have the same chirality for
      of the two strands. Each Cu(II) metal center is six-coordinated according to a
      cis-octahedral geometry and interacts with a NNO donor subunit of each strand.
      The Cu(I) complex, when crystallized from THF in the presence of (rac)5, gives a
      double-strand homochiral helicate complex and in the solid state forms a racemic
      mixture of the homochiral metal complexes M,M-[Cu(2)(I)((RR)5)(2)](2+) and P,P
      [Cu(2)(I)((SS)5)(2)](2+). When crystallizing from a MeCN solution, Cu(I) and
      (rac)5 give rise to the heterochiral nonhelicate dimeric complex
      [Cu(2)(I)((RR)5)((SS)5)](2+), in which the two strands of the dimer have inverse
      configuration of the trans-1,2-cyclohexanediamine subunits and are assembled side
      by-side. In both structural architectures, the Cu(I) centers are four-coordinated
      by two nitrogen atoms from each strand, according to a distorted tetrahedral
      geometry. In MeCN solution, the dinuclear Cu(II) complex disassembles to give the
      mononuclear species, which, on reduction at a platinum electrode in a cyclic
      voltammetry experiment, gives two Cu(I) mononuclear complexes that quickly
      assemble to give the dinuclear Cu(I) complex. This complex undergoes two
      consecutive one-electron oxidation processes, but the dinuclear Cu(II) species
      that forms decomposes in less than 1 s. On the contrary, the
      [Cu(2)(I)((rac)5)(2)](2+) complex is stable in MeCN solution and undergoes two
      one-electron oxidation processes to give a form of dinuclear Cu(II) complex that
      lasts in solution for more than 20 s.

PMID- 20030373
TI  - Reactions of monodithiolene tungsten(VI) sulfido complexes with copper(I) in
      relation to the structure of the active site of carbon monoxide dehydrogenase.
AB  - Reactions directed at the synthesis of structural analogues of the active site of
      molybdenum-containing carbon monoxide dehydrogenase have been investigated
      utilizing [WO(2)S(bdt)](2-) (1) and [WOS(2)(bdt)](2-) (2) and sterically hindered
      [Cu(R)L] or [Cu(SSiR'(3))(2)](-) as reactants. All successful reactions of 2
      afford the binuclear W(VI)/Cu(I) products [WO(bdt)(mu(2)-S)(2)Cu(L)](2-/-) with L
      = carbene (3), Ar*S (4), Ar* (7), SSiR(3) (R = Ph (5), Pr(i) (6)). Similarly,
      [W(bdt)(OSiPh(3))S(2)](-) leads to [W(bdt)(OSiPh(3))(mu(2)-S)(2)Cu(SAr*)](-) (8).
      These complexes, with apical oxo and basal dithiolato and sulfido coordination
      (excluding 8), terminal thiolate ligation at Cu(I) (4-6, 8), and W-(mu(2)-S)-Cu
      bridging, bear a structural resemblance to the enzyme site. Differences include
      two bridges instead of one and the absence of basal oxo/hydroxo ligation. Complex
      8 differs from the others by utilizing apical and basal sulfido ligands in bridge
      formation. Related reaction systems based on 1 gave 4 in small yield or product
      mixtures in which the desired monobridged complex [WO(2)(bdt)(mu(2)-S)Cu(R)](2-)
      was not detected. Mass spectrometric analysis of the reaction system with L =
      carbene suggests that any monobridged species forms may converted to the
      dibridged form by disproportionation. In these experiments, the use of W(VI)
      preserves the structural integrity of Mo(VI), whose analogues of 1 and 2 have not
      been isolated. (Ar* = 2,6-bis(2,4,6-triisopropylphenyl)phenyl, bdt = benzene-1,2
      dithiolate(2-)).

PMID- 20030374
TI  - Structural diversity by mixing chalcogen atoms in the chalcophosphate system
      K/In/P/Q (Q = S, Se).
AB  - The new thiophosphate salt K(4)In(2)(PS(4))(2)(P(2)S(6)) (1), the selenophosphate
      salts K(5)In(3)(mu(3)-Se)(P(2)Se(6))(3) (2), K(4)In(4)(mu-Se)(2)(P(2)Se(6))(3)
      (3), and the mixed seleno-/thiophosphate salt K(4)In(4)(mu
      Se)(P(2)S(2.36)Se(3.64))(3) (4) are described. For the first time, a structurally
      different outcome of a chalcophosphate reaction was observed when sulfur and
      selenium are mixed, for example, by the use of K(2)S/P(2)Se(5)/S/In instead of
      K(2)Se/P(2)Se(5)/Se/In or K(2)S/P(2)S(5)/S/In. In compounds 1-4 indium atoms
      exist in a variety coordination environments. While in 1, indium is octahedrally
      coordinated, in 2-4 tetrahedral, trigonal-bipyramidal, and octahedral
      coordination environments are found for indium atoms. This remarkable structural
      diversity possibly is a reason, why particularly indium chalcophosphate flux
      reactions often produce a large variety of compounds at intermediate
      temperatures. In the mixed seleno-/thiophosphate salt K(4)In(4)(mu
      Se)(P(2)S(2.36)Se(3.64))(3) (4) most of the chalcogen sites around the
      tetrahedrally coordinated P atoms show mixed S/Se occupancy. There is, however, a
      preference for Se binding to In ions and S binding to potassium ions.

PMID- 20030376
TI  - Synthesis and characterization of iron(II) quinaldate complexes.
AB  - Treatment of iron(II) chloride or iron(II) bromide with 2 equiv of sodium
      quinaldate (qn = quinaldate or C(10)H(6)NO(2)(-)) yields the coordinatively
      unsaturated mononuclear iron(II) quinaldate complexes Na[Fe(II)(qn)(2)Cl].DMF and
      Na[Fe(II)(qn)(2)Br].DMF (DMF = N,N-dimethylformamide), respectively. When a
      similar synthesis is carried out using iron(II) triflate, a solvent-derived
      linear triiron(II) complex, [Fe(II)(3)(qn)(6)(DMF)(2)], with two five-coordinate
      iron(II) centers and a single six-coordinate iron(II) center is obtained. Each of
      these species has been characterized using X-ray diffraction. The vibrational
      features of these complexes are consistent with the observed solid-state
      structures. Each of these compounds exhibits an iron(II)-to-quinaldate (pi*)
      charge-transfer band between 520 and 550 nm. These metal-to-ligand charge
      transfer bands are sensitive to substitution of the quinaldates as well as
      alteration of the first coordination sphere ligands. However, the (1)H NMR
      spectra of these paramagnetic high-spin iron(II) complexes are not consistent
      with retention of the solid-state structures in a DMF solution. The chemical
      shifts, longitudinal relaxation times (T(1)), relative integrations, and
      substitution of the quinaldate ligands provide a means to fully assign the (1)H
      NMR spectra of the paramagnetic materials. These spectra are consistent with
      coordination equilibria between five- and six-coordinate species in a DMF
      solution. Electrochemical studies are reported to place these oxygen-sensitive
      compounds in a broader context with other iron(II) compounds. Iron complexes of
      bidentate quinoline-2-carboxylate-derived ligands are germane to metabolic
      pathways, environmental remediation, and catalytic applications.

PMID- 20030375
TI  - Eribulin binds at microtubule ends to a single site on tubulin to suppress
      dynamic instability.
AB  - Eribulin mesylate (E7389), a synthetic analogue of the marine natural product
      halichondrin B, is in phase III clinical trials for the treatment of cancer.
      Eribulin targets microtubules, suppressing dynamic instability at microtubule
      plus ends through an inhibition of microtubule growth with little or no effect on
      shortening [Jordan, M. A., et al. (2005) Mol. Cancer Ther. 4, 1086-1095]. Using
      [(3)H]eribulin, we found that eribulin binds soluble tubulin at a single site;
      however, this binding is complex with an overall K(d) of 46 microM, but also
      showing a real or apparent very high affinity (K(d) = 0.4 microM) for a subset of
      25% of the tubulin. Eribulin also binds microtubules with a maximum stoichiometry
      of 14.7 +/- 1.3 molecules per microtubule (K(d) = 3.5 microM), strongly
      suggesting the presence of a relatively high-affinity binding site at microtubule
      ends. At 100 nM, the concentration that inhibits microtubule plus end growth by
      50%, we found that one molecule of eribulin is bound per two microtubules,
      indicating that the binding of a single eribulin molecule at a microtubule end
      can potently inhibit its growth. Eribulin does not suppress dynamic instability
      at microtubule minus ends. Preincubation of microtubules with 2 or 4 microM
      vinblastine induced additional lower-affinity eribulin binding sites, most likely
      at splayed microtubule ends. Overall, our results indicate that eribulin binds
      with high affinity to microtubule plus ends and thereby suppresses dynamic
      instability.

PMID- 20030377
TI  - Decoding the nitrogenase mechanism: the homologue approach.
AB  - The (Mo)-nitrogenase is a complex metalloenzyme that catalyzes the key step in
      the global nitrogen cycle, the reduction of atmospheric dinitrogen (N(2)) to
      bioavailable ammonia (NH(3)), at the iron-molybdenum cofactor (FeMoco) site of
      its molybdenum-iron (MoFe) protein component. Despite the fundamental
      significance of biological nitrogen fixation and extensive studies over the past
      decades, the catalytic mechanism of nitrogenase has not been deciphered. One
      major challenge for the mechanistic study of nitrogenase is the redox versatility
      of its FeMoco center. The ability of FeMoco to shuttle between oxidation states
      in a rapid and unsynchronized manner results in a mixed oxidation state of the
      cofactor population during turnover. The substrate and the various intermediates
      can only interact with the FeMoco site in a transient manner, so it is extremely
      difficult to capture any substrate- or intermediate-bound form of nitrogenase for
      the direct examination of substrate-enzyme interactions during catalysis. In this
      Account, we describe the approach of identifying a partially "defective"
      nitrogenase homologue, one with a slower turnover rate, as a means of overcoming
      this problem. The NifEN protein complex serves as an ideal candidate for this
      purpose. It is an alpha(2)beta(2)-heterotetramer that contains cluster-binding
      sites homologous to those found in the MoFe protein: the "P-cluster site" at the
      interface of the alphabeta-subunit dimer, which accommodates a [Fe(4)S(4)]-type
      cluster; and the "FeMoco site" within the alpha-subunit, which houses an all-iron
      homologue to the FeMoco. Moreover, NifEN mimics the MoFe protein in catalysis: it
      is capable of reducing acetylene (C(2)H(2)) and azide (N(3)(-)) in an ATP- and
      iron (Fe) protein-dependent manner. However, NifEN is unable to reduce proton
      (H(+)) and N(2), and it is an inefficient enzyme with a restricted electron flux
      during the turnover. The extremely slow turnover rate of NifEN and the possible
      "synchronization" of its FeMoco homologue at a certain oxidation level permit the
      observation of a new S = 1/2 EPR signal upon turnover of C(2)H(2) by NifEN, which
      is analogous to the signal reported for a MoFe protein variant upon turnover of
      the same substrate. This result is exciting, because it suggests the possibility
      of naturally enriching a C(2)H(2)-bound form of NifEN for the successful
      crystallization of the first intermediate-bound nitrogenase homologue. On the
      other hand, the fact that NifEN represents a partially "defective" homologue of
      the MoFe protein makes it a promising mutational platform on which a functional
      MoFe protein equivalent may be reconstructed by introducing the missing features
      of MoFe protein step-by-step into NifEN. Such a strategy allows us to define the
      function of each feature and address questions such as the following: What is the
      function of P-cluster in catalysis? Are Mo and homocitrate the essential
      constituents of the cofactor in N(2) reduction? How does substrate accessibility
      affect the reactivity of the enzyme? This homologue approach could complement the
      mechanistic analysis of the nitrogenase MoFe protein, and information derived
      from both approaches will help achieve the ultimate goal of solving the riddle of
      biological nitrogen fixation.

PMID- 20030378
TI  - Tracking chemical processing pathways in combinatorial polymer libraries via data
      mining.
AB  - Changes in the molecular structure and composition of interpenetrating polymer
      networks (IPNs) can be used to tailor their properties. While the properties of
      IPNs are typically different than polymer blends, a clear understanding of the
      impact of changing polymerization sequence on the physical properties and the
      corresponding molecular bonding is needed. To address this issue, a data mining
      approach is used to identify the change with polymerization sequence of tensile
      and rheological properties of acrylate-epoxy IPNs. The experimental approach used
      to study the molecular structure is high throughput Fourier transform infrared
      (FTIR) spectroscopy. Analysis of the FTIR spectra of IPNs synthesized with
      different polymerization sequences leads to an understanding of the molecular
      bonding responsible for the tensile and rheological properties. From the
      interpretation of the wavenumber bands and associated molecular bonds, we find
      that the polymerization sequence most affects hydrogen bonding and aromatic ring
      bond energies. This work defines the relationships between chemistry, structure,
      processing, and properties of the IPN samples.

PMID- 20030379
TI  - Significance of biological hydrogen oxidation in a continuous single-chamber
      microbial electrolysis cell.
AB  - A single-chamber microbial electrolysis cell (MEC) that used a high density of
      nonmetal-catalyst carbon fibers as the anode achieved high volumetric current
      densities from 1470 +/- 60 to 1630 +/- 50 A/m(3) for a hydraulic retention time
      of 1.6-6.5 h. The high current density was driven by a large anode surface area
      and corresponded to a volumetric chemical oxygen demand (COD)-removal rate of 27
      49 kg COD/m(3).d. Observed H(2) harvesting rates were from 2.6 +/- 0.10 to 4.3 +/
      0.46 m(3) H(2)/m(3).d, but the H(2) production rates computed from the current
      densities were 16.3-18.2 m(3) H(2)/m(3).d. Tracking all significant electron
      sinks (residual acetate, H(2), CH(4), biomass, and soluble microbial products
      (SMP)) in the single-chamber MEC showed that H(2) reoxidation by anode-respiring
      bacteria recycled H(2) between the cathode and the anode, and this caused the
      large discrepancy in H(2) production and harvest rates. H(2) recycle accounted
      for 62-76% of observed current density, and this made the observed Coulombic
      efficiency 190-310% at steady state. Consequently, the cathodic conversion
      efficiency was only 16-24%. The current density added by H(2) recycle also
      increased the applied voltage from approximately 0.6 V to approximately 1.5 V for
      the highest H(2) harvest rate (4.3 m(3) H(2)/m(3).d). CH(4) generation
      consistently occurred in the continuous single-chamber MEC, and its electron
      fraction of consumed acetate was 7-25%. Because of methane formation and
      biomass/SMP accumulation, the overall H(2) recovery was moderate at 1.8-2.0 mol
      of H(2)/mol of acetate in the MEC. Thus, this study illustrates that a single
      chamber MEC with a high anode surface area can generate high volumetric rates for
      COD removal and H(2) generation, but H(2) recycle and methanogenesis present
      significant challenges for practical application.

PMID- 20030380
TI  - Urinary bisphenol A concentrations in relation to serum thyroid and reproductive
      hormone levels in men from an infertility clinic.
AB  - Human exposure to bisphenol A (BPA) is widespread. Animal studies have
      demonstrated that BPA can alter endocrine function, but human studies are
      limited. For the present study, we measured urinary BPA concentrations and serum
      thyroid and reproductive hormone levels in 167 men recruited through an
      infertility clinic. BPA was detected in 89% of urine samples with a median
      (range) of 1.3 (<0.4 - 36.4) ng/mL. In multivariable regression models adjusted
      for potential confounders, BPA concentrations in urine collected on the same day
      as a blood sample were inversely associated with serum levels of inhibin B and
      estradiol:testosterone ratio (E(2):T) and positively associated with follicle
      stimulating hormone (FSH) and FSH:inhibin B ratio. Because BPA is metabolized
      quickly and multiple urine measures may better reflect exposure than a single
      measure, we also considered among a subset of the men the BPA concentrations in
      repeated urine samples collected weeks or months following serum sample
      collection. In these analyses, the effect estimates remained consistent for FSH
      and E(2):T but were somewhat weakened for inhibin B. In addition, we observed
      inverse relationships between urinary BPA concentrations and free androgen index
      (ratio of testosterone to sex hormone binding globulin), estradiol, and thyroid
      stimulating hormone. Our results suggest that urinary BPA concentrations may be
      associated with altered hormone levels in men, but these findings need to be
      substantiated through further research.

PMID- 20030381
TI  - DNA interstrand cross-linking activity of (1-Chloroethenyl)oxirane, a metabolite
      of beta-chloroprene.
AB  - With the goal of elucidating the molecular and cellular mechanisms of chloroprene
      toxicity, we examined the potential DNA cross-linking of the bifunctional
      chloroprene metabolite, (1-chloroethenyl)oxirane (CEO). We used denaturing
      polyacrylamide gel electrophoresis to monitor the possible formation of
      interstrand cross-links by CEO within synthetic DNA duplexes. Our data suggest
      interstrand cross-linking at deoxyguanosine residues within 5'-GC and 5'-GGC
      sites, with the rate of cross-linking depending on pH (pH 5.0 > pH 6.0 > pH 7.0).
      A comparison of the cross-linking efficiencies of CEO and the structurally
      similar cross-linkers diepoxybutane (DEB) and epichlorohydrin (ECH) revealed that
      DEB > CEO > or = ECH. Furthermore, we found that cytotoxicity correlates with
      cross-linking efficiency, supporting a role for interstrand cross-links in the
      genotoxicology of chloroprene.

PMID- 20030382
TI  - Sensitized emission of luminescent lanthanide complexes based on a phosphane
      oxide derivative.
AB  - The photophysical properties of a complex based on diphenylphosphanoethane (DPPE)
      fluorescent ligands linked to a europium ion have been investigated by different
      spectroscopic methods. Upon complexation with europium, the interaction of the
      phosphane oxide group with europium leads to a red shift of the absorption
      spectrum and a strong quenching of the ligand emission. The typical sensitized
      emission of Eu(3+) is observed upon excitation of the ligand with a fluorescence
      quantum yield of 1%. Time-resolved absorption and emission experiments have been
      performed in order to investigate the photophysical mechanism involved in this
      complex. Photophysical studies show that an energy-transfer mechanism occurs from
      both the first excited singlet and triplet states of the ligand, and the
      population of the europium ion to the (5)D(1) state takes place, from which the
      (5)D(0) state is populated. Additionally, electron transfer from the excited
      singlet state of the ligand to the europium ion appears as a very efficient
      process.

PMID- 20030383
TI  - Impact of the incorporation of Au nanoparticles into polymer/fullerene solar
      cells.
AB  - The addition of small amounts of dodecylamine-capped Au nanoparticles into the
      active layer of organic bulk heterojunction solar cells consisting of poly(3
      octylthiophene) (P3OT) and C(60) was recently suggested to have a positive impact
      on device performance due to improved electron transport. This issue was
      systematically further investigated in the present work. Different strategies to
      incorporate colloidally prepared Au nanoparticles with a narrow size distribution
      into organic solar cells with the more common donor/acceptor system consisting of
      poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C(61)-butyric acid methyl ester
      (PCBM) were pursued. Au nanoparticles were prepared with either P3HT or
      dodecylamine as ligands. Additionally, efforts were undertaken to incorporate
      nearly ligand-free Au nanoparticles into the system. Therefore, a procedure was
      successfully developed to remove the dodecylamine ligand shell by a
      postpreparative ligand exchange with pyridine, a much smaller molecule that can
      later partly be removed from solid films by annealing. However, for all types of
      nanoparticles studied here, the performance of the P3HT/PCBM solar cells was
      found to decrease with the Au particles as an additive to the active layer,
      meaning that adding Au nanoparticles is not a suitable strategy in the case of
      the P3HT/PCBM system. Possible reasons are discussed on the basis of detailed
      investigations of the structure, photophysics and charge transport in the system.

PMID- 20030384
TI  - Effect of liberibacter infection (huanglongbing disease) of citrus on orange
      fruit physiology and fruit/fruit juice quality: chemical and physical analyses.
AB  - More than 90% of oranges in Florida are processed, and since Huanglongbing (HLB)
      disease has been rumored to affect fruit flavor, chemical and physical analyses
      were conducted on fruit and juice from healthy (Las -) and diseased (Las +) trees
      on three juice processing varieties over two seasons, and in some cases several
      harvests. Fruit, both asymptomatic and symptomatic for the disease, were used,
      and fresh squeezed and processed/pasteurized juices were evaluated. Fruit and
      juice characteristics measured included color, size, solids, acids, sugars, aroma
      volatiles, ascorbic acid, secondary metabolites, pectin, pectin-demethylating
      enzymes, and juice cloud. Results showed that asymptomatic fruit from symptomatic
      trees were similar to healthy fruit for many of the quality factors measured, but
      that juice from asymptomatic and especially symptomatic fruits were often higher
      in the bitter compounds limonin and nomilin. However, values were generally below
      reported taste threshold levels, and only symptomatic fruit seemed likely to
      cause flavor problems. There was variation due to harvest date, which was often
      greater than that due to disease. It is likely that the detrimental flavor
      attributes of symptomatic fruit (which often drop off the tree) will be largely
      diluted in commercial juice blends that include juice from fruit of several
      varieties, locations, and seasons.

PMID- 20030385
TI  - The new face of rhodium alloys: revealing ordered structures from first
      principles.
AB  - The experimental and computational data on rhodium binary alloys is sparse
      despite its importance in numerous applications, especially as an alloying agent
      in catalytic materials. Half of the Rh-transition metal systems (14 out of 28)
      are reported to be phase separating or are lacking experimental data.
      Comprehensive high-throughput first-principles calculations predict stable
      ordered structures in 9 of those 14 binary systems. They also predict a few
      unreported compounds in the known compound-forming systems. These results
      indicate the need for an extensive revision of our current understanding of Rh
      alloys through a combination of theoretical predictions and experimental
      validations.

PMID- 20030386
TI  - Three-component synthesis of perfluoroalkyl- or perfluoroaryl-substituted 4
      hydroxypyridine derivatives and their palladium-catalyzed coupling reactions.
AB  - A three-component reaction with lithiated alkoxyallenes, nitriles, and
      perfluorinated carboxylic acids as precursors led to a series of perfluoroalkyl-
      or perfluoroaryl-substituted 4-hydroxypyridine derivatives. These compounds were
      converted into 4-pyridyl nonaflates which can be employed as versatile building
      blocks for the synthesis of pi-conjugated compounds with use of palladium
      catalyzed couplings. Suzuki reactions at C-4 and C-3 of the pyridine ring
      proceeded with moderate to high yields. In addition, Suzuki-Miyaura, Stille, or
      Buchwald-Hartwig coupling reactions have also been studied and afforded the
      corresponding highly substituted pyridine derivatives. Starting from an arylated
      propargylic ether the three-component reaction led to a pentasubstituted 4
      hydroxypyridine derivative that could also be employed in palladium-catalyzed
      processes at C-4 and at C-3 of the pyridine core. With this simple approach the
      sterically highly crowded 3,4,5-triphenyl-substituted pyridine derivative 37a
      could be prepared and studied by an X-ray analysis. With acetonitrile as
      precursor a different reaction pathway was found when this component was used in
      excess resulting in a pyridine derivative with a new substitution pattern. In
      summary, the methods described here allow a flexible and fairly efficient entry
      to a variety of highly substituted pyridine derivatives bearing perfluorinated
      alkyl or aryl groups.

PMID- 20030387
TI  - Mechanistic detail revealed via comprehensive kinetic modeling of [rac-C(2)H4(1
      indenyl)2ZrMe2]-catalyzed 1-hexene polymerization.
AB  - Thorough kinetic characterization of single-site olefin polymerization catalysis
      requires comprehensive, quantitative kinetic modeling of a rich multiresponse
      data set that includes monomer consumption, molecular weight distributions
      (MWDs), end group analysis, etc. at various conditions. Herein we report the
      results obtained via a comprehensive, quantitative kinetic modeling of all
      chemical species in the batch polymerization of 1-hexene by rac-C(2)H(4)(1
      Ind)(2)ZrMe(2) activated with B(C(6)F(5))(3). While extensive studies have been
      published on this catalyst system, the previously acknowledged kinetic mechanism
      is unable to predict the MWD. We now show it is possible to predict the entire
      multiresponse data set (including the MWDs) using a kinetic model featuring a
      catalytic event that renders 43% of the catalyst inactive for the duration of the
      polymerization. This finding has significant implications regarding the behavior
      of the catalyst and the polymer produced and is potentially relevant to other
      single-site polymerization catalysts, where it would have been undetected as a
      result of incomplete kinetic modeling. In addition, comprehensive kinetic
      modeling of multiresponse data yields robust values of rate constants
      (uncertainties of less than 16% for this catalyst) for future use in developing
      predictive structure-activity relationships.

PMID- 20030388
TI  - Nanohole chains for directional and localized surface plasmon excitation.
AB  - Arrangements of subwavelength sized holes in metal films are often used to launch
      surface plasmon polaritons (SPPs) onto metal-dielectric interfaces. They are
      readily fabricated and can also be used to generate a variety of near- and far
      field intensity patterns. We use a short chain of equally spaced subwavelength
      sized holes to launch SPPs onto a gold-air interface in complex patterns of
      hotspots. With a phase-sensitive near-field microscope, we visualize the electric
      field of the excited SPPs. We observe self-images of the chain that we attribute
      to the Talbot effect. Far from the chain we observe the SPP diffraction orders.
      We find that when the spacing of the holes is of the order of the wavelength, the
      revivals do not occur on the well-known Talbot distance as derived in the
      paraxial limit. We present an alternative expression for the Talbot distance that
      does hold for these small spacings. We study the behavior of both the revivals
      and the diffraction orders as a function of the number of holes. We find that the
      Talbot revivals become more pronounced as the number of holes is increased, which
      is in accordance with numerical calculations. We anticipate that our findings are
      interesting for multiplexing sensor applications, where control over the local
      intensity of SPPs is crucial.

PMID- 20030389
TI  - Norfloxacin sorption and its thermodynamics on surface-modified carbon nanotubes.
AB  - Adsorption on carbon nanotubes (CNTs) may affect the environmental behavior of
      organic contaminants including antibiotics. In this study, sorption of
      norfloxacin (NOR) onto graphitized multiwall CNTs (G-CNTs), carboxylated
      multiwall CNTs (C-CNTs), hydroxylated multiwall CNTs (H-CNTs), and activated
      carbon (AC) was investigated. All sorption isotherms were highly nonlinear and
      were fitted well by Freundlich and Polanyi-Manes models. AC showed the highest
      NOR sorption capacity because of its highest surface area. H-CNTs had much higher
      NOR sorption than C-CNTs, and the pi-pi electron donor-acceptor (EDA)
      interactions could explain the distinction between the two types of CNTs.
      Comparison of sorption coefficients at different pHs indicates that hydrophobic
      and electrostatic interaction also played major roles in sorption of NOR on CNTs.
      Furthermore, high sorption capacity and hysteresis of NOR on CNTs were
      demonstrated in this study, which needs to be considered for predicting
      environmental risks of CNTs and NOR. The results from thermodynamic analysis show
      that sorption of NOR on AC and CNTs was thermodynamically favorable and generally
      endothermic. Sorption site energy analysis illustrates a distribution of sorption
      energy, consistent with nonlinear isotherms, which indicates the heterogeneous
      sites on CNTs for NOR adsorption.

PMID- 20030390
TI  - Effects of cosolvents on the hydration of carbon nanotubes.
AB  - Molecular dynamics simulations of a nonpolar single-walled carbon nanotube (SWNT)
      solvated in aqueous solutions of urea, methanol, and trimethylamine N-oxide
      (TMAO) show clearly the effects of cosolvents on the hydration of the interior of
      the SWNT. The size of the SWNT was chosen to be small enough that water but not
      the cosolvent molecules can penetrate into its interior. Urea as a protein
      denaturant improves hydration of the interior of the SWNT, while the protein
      protectant TMAO dehydrates the SWNT. The interior of the SWNT is also dehydrated
      when methanol is added to the solution. The analysis of interaction energies of
      the water confined inside the SWNT pore shows that the stability of the confined
      water in the methanol and TMAO solutions mainly depends on electrostatic
      interactions. In contrast, both van der Waals and electrostatic interactions were
      shown to be important in stabilizing the confined water when the SWNT is immersed
      in the urea solution.

PMID- 20030391
TI  - Alignment, rotation, and spinning of single plasmonic nanoparticles and nanowires
      using polarization dependent optical forces.
AB  - We demonstrate optical alignment and rotation of individual plasmonic
      nanostructures with lengths from tens of nanometers to several micrometers using
      a single beam of linearly polarized near-infrared laser light. Silver nanorods
      and dimers of gold nanoparticles align parallel to the laser polarization because
      of the high long-axis dipole polarizability. Silver nanowires, in contrast,
      spontaneously turn perpendicular to the incident polarization and predominantly
      attach at the wire ends, in agreement with electrodynamics simulations. Wires,
      rods, and dimers all rotate if the incident polarization is turned. In the case
      of nanowires, we demonstrate spinning at an angular frequency of approximately 1
      Hz due to transfer of spin angular momentum from circularly polarized light.

PMID- 20030392
TI  - Topological insulator nanowires and nanoribbons.
AB  - Recent theoretical calculations and photoemission spectroscopy measurements on
      the bulk Bi(2)Se(3) material show that it is a three-dimensional topological
      insulator possessing conductive surface states with nondegenerate spins,
      attractive for dissipationless electronics and spintronics applications.
      Nanoscale topological insulator materials have a large surface-to-volume ratio
      that can manifest the conductive surface states and are promising candidates for
      devices. Here we report the synthesis and characterization of high quality single
      crystalline Bi(2)Se(3) nanomaterials with a variety of morphologies. The
      synthesis of Bi(2)Se(3) nanowires and nanoribbons employs Au-catalyzed vapor
      liquid-solid (VLS) mechanism. Nanowires, which exhibit rough surfaces, are formed
      by stacking nanoplatelets along the axial direction of the wires. Nanoribbons are
      grown along [1120] direction with a rectangular cross-section and have diverse
      morphologies, including quasi-one-dimensional, sheetlike, zigzag and sawtooth
      shapes. Scanning tunneling microscopy (STM) studies on nanoribbons show
      atomically smooth surfaces with approximately 1 nm step edges, indicating single
      Se-Bi-Se-Bi-Se quintuple layers. STM measurements reveal a honeycomb atomic
      lattice, suggesting that the STM tip couples not only to the top Se atomic layer,
      but also to the Bi atomic layer underneath, which opens up the possibility to
      investigate the contribution of different atomic orbitals to the topological
      surface states. Transport measurements of a single nanoribbon device (four
      terminal resistance and Hall resistance) show great promise for nanoribbons as
      candidates to study topological surface states.

PMID- 20030393
TI  - New series of ruthenium(II) and osmium(II) complexes showing solid-state
      phosphorescence in far-visible and near-infrared.
AB  - A new Ru(II) complex, [Ru(fpbpymH)(2)]Cl(2) (1), in which fpbpymH = [5
      (trifluoromethyl)pyrazol-3-yl](2,2'-bipyrid-6-yl)methane, was prepared by the
      treatment of [Ru(DMSO)(4)Cl(2)] with 2 equiv of the terdentate chelate fpbpymH in
      refluxing ethanol. A single-crystal X-ray diffraction study of 1 revealed a
      distorted octahedral Ru(II) framework, showing strong N-H...Cl hydrogen bonding
      between the fpbpymH ligand and Cl anions. In the presence of Na(2)CO(3), the
      methylene linkers of chelates in 1 underwent stepwise oxygenation, forming the
      charge-neutral complexes [Ru(fpbpym)(fpbpyk)] (2) and [Ru(fpbpyk)(2)] (3)
      [fpbpykH = [5-(trifluoromethyl)pyrazol-3-yl](2,2'-bipyrid-6-yl) ketone] in
      sequence. The respective charge-neutral Os(II) complex [Os(fpbpyk)(2)] (4) was
      also isolated by the treatment of OsCl(3).3H(2)O with 2 equiv of the terdentate
      chelate fpbpymH. Electrochemical analysis indicated that the introduction of the
      electron-withdrawing ketone group in 2-4 increased the metal-based oxidation
      potential in sequence. For the photophysical properties, complexes 1-4 are
      essentially nonluminescent in solution (e.g., CH(2)Cl(2) or MeOH) at room
      temperature, but all exhibit 600-1100 nm phosphorescence with moderate intensity
      for the powdery, solid sample at room temperature. The trend in terms of the
      emission peak wavelength of 1 (666 nm) < 3 (795 nm) < 2 (810 nm) < 4 (994 nm)
      among titled complexes is in agreement with the corresponding onset of absorption
      spectra as well as the time-dependent density functional theory calculation of 1
      < 3 < 2 < 4.

PMID- 20030394
TI  - Infrared spectroscopy of hydrated bicarbonate anion clusters: HCO3(-)(H2O)(1-10).
AB  - Infrared multiple photon dissociation spectra are reported for HCO(3)(-)(H(2)O)(1
      10) clusters in the spectral range of 600-1800 cm(-1). In addition, electronic
      structure calculations at the MP2/6-311+G(d,p) level have been performed on the n
      = 1-8 clusters to identify the structure of the low-lying isomers and to assign
      the observed spectral features. General trends in the stepwise solvation motifs
      of the bicarbonate anion can be deduced from the overall agreement between the
      calculated and experimental spectra. The most important of these is the strong
      preference of the water molecules to bind to the negatively charged CO(2) moiety
      of the HCO(3)(-) anion. However, a maximum of four water molecules interact
      directly with this site. The binding motif in the most stable isomer of the n = 4
      cluster, a four-membered ring with each water forming a single H-bond with the
      CO(2) moiety, is retained in all of the lowest-energy isomers of the larger
      clusters. Starting at n = 6, additional solvent molecules are found to form a
      second hydration layer, resulting in a water-water network bound to the CO(2)
      moiety of the bicarbonate anion. Binding of a water to the hydroxyl group of
      HCO(3)(-) is particularly disfavored and apparently does not occur in any of the
      clusters investigated here. Similarities and differences with the infrared
      spectrum of aqueous bicarbonate are discussed in light of these trends.

PMID- 20030395
TI  - Tunable nanoscale graphene magnetometers.
AB  - The detection of magnetic fields with nanoscale resolution is a fundamental
      challenge for scanning probe magnetometry, biosensing, and magnetic storage.
      Current technologies based on giant magnetoresistance and tunneling
      magnetoresistance are limited at small sizes by thermal magnetic noise and spin
      torque instability. These limitations do not affect Hall sensors consisting of
      high mobility semiconductors or metal thin films, but the loss of magnetic flux
      throughout the sensor's thickness greatly limits spatial resolution and
      sensitivity. Here we demonstrate graphene extraordinary magnetoresistance devices
      that combine the Hall effect and enhanced geometric magnetoresistance, yielding
      sensitivities rivaling that of state of the art sensors but do so with
      subnanometer sense layer thickness at the sensor surface. Back-gating provides
      the ability to control sensor characteristics, which can mitigate both inherent
      variations in material properties and fabrication-induced device-to-device
      variability that is unavoidable at the nanoscale.

PMID- 20030396
TI  - Direct observation of the pH-dependent equilibrium between metarhodopsins I and
      II and the pH-independent interaction of metarhodopsin II with transducin C
      terminal peptide.
AB  - Bovine rhodopsin contains 11-cis-retinal as a light-absorbing chromophore that
      binds to a lysine residue of the apoprotein opsin via a protonated Schiff base
      linkage. Light isomerizes 11-cis-retinal into the all-trans form, which
      eventually leads to the formation of an enzymatically active state, metarhodopsin
      II (MII). It is widely believed that MII forms a pH-dependent equilibrium with
      metarhodopsin I (MI), but direct evidence for this equilibrium has not been
      reported. Here, we confirmed this equilibrium by direct observation of the mutual
      conversions of MI and MII upon changing the pH of the MI/MII mixture. We also
      observed a reversible binding of the synthetic peptide constituting the C
      terminal 11 amino acids of the transducin alpha-subunit to MII, which resulted in
      change of the amounts of MI and MII in the equilibrium. Interestingly, addition
      of the peptide did not induce a simple pK(a) shift but rather induced an increase
      of the MII fraction at high pH. These results indicate that in addition to the
      MII that is formed from MI in a pH-dependent manner there also exists another
      MII, which is in equilibrium with MI in a pH-independent manner and can bind to
      the peptide. Therefore, there is no need for proton uptake by the protein moiety
      of opsin for the binding to the peptide.

PMID- 20030397
TI  - Electronic properties of the 2,6-diiododithieno[3,2-b:2',3'-d]thiophene molecule
      and crystal: a joint experimental and theoretical study.
AB  - The electronic properties of the 2,6-diiododithieno[3,2-b:2',3'-d] thiophene
      molecule and crystal are investigated by means of UV-vis spectroscopy, cyclic
      voltammetry, X-ray crystallography, and density functional theory. The
      experimental and calculated properties of the compound are compared to those
      exhibited by the parent molecule, dithieno[3,2-b:2',3'-d]thiophene. Quantum
      chemical studies of the 2,6-diiododithieno[3,2-b:2',3'-d]thiophene crystal
      suggest uniaxial hole-transport character with an effective mass of about 2m(0),
      comparable to that in the pentacene single crystal.

PMID- 20030398
TI  - Dimers of quadrupolar chromophores in solution: electrostatic interactions and
      optical spectra.
AB  - Two dimers of a heteroaromatic quadrupolar (acceptor-donor-acceptor) chromophore
      have been synthesized with different interchromophoric distances. Optical spectra
      of dimers in solution show a red shift of the linear absorption band upon
      decreasing the interchromophore distance, while fluorescence and two-photon
      absorption spectra are only marginally affected by the interactions. A bottom up
      approach is adopted to describe the spectra: via a detailed spectroscopic
      analysis of the monomeric species in solution, we define an essential-state model
      for the isolated chromophore and use this information to set up a model for the
      dimers also accounting for interchromophore electrostatic interactions. To
      discriminate between static screening governed by the static dielectric constant
      and dynamical screening at optical frequencies, we first solve the problem in the
      mean-field approximation and then define the excitonic Hamiltonian on the
      resulting best excitonic basis. Along this line, the evolution of spectral
      properties with the interchromophore distance is properly rationalized.

PMID- 20030399
TI  - GlycoSpectrumScan: fishing glycopeptides from MS spectra of protease digests of
      human colostrum sIgA.
AB  - With the emergence of glycoproteomics, there is a need to develop bioinformatic
      tools to identify glycopeptides in protease digests of glycoproteins.
      GlycoSpectrumScan is a web-based tool that identifies the glycoheterogeneity on a
      peptide from mass spectrometric data. Two experimental data sets are required as
      inputs: (1) oligosaccharide compositions of the N- and/or O-linked glycans
      present in the sample and (2) in silico derived peptide masses of proteolytically
      digested proteins with a potential number of N- and/or O-glycosylation sites.
      GlycoSpectrumScan uses MS data, rather than MS/MS data, to identify glycopeptides
      and determine the relative distribution of N- and O-glycoforms at each site. It
      is functional for assigning monosaccharide compositions on glycopeptides with
      single and multiple sites of glycosylation. The algorithm allows the input of raw
      mass data, including multiply charged ions, making it applicable for both ESI and
      MALDI data from all mass spectrometer platforms. Manual analysis time for
      identifying glycosylation heterogeneity at each site on glycoprotein(s) is
      substantially decreased. The application of this tool to characterize the N- and
      O-linked glycopeptides from human secretory IgA (sIgA), consisting of secretory
      component (7 N-linked sites), IgA1 (2 N-linked, <or=5 O-linked sites), IgA2 (4 N
      linked sites) and J-chain (1 N-linked site) is described. GlycoSpectrumScan is
      freely available at www.glycospectrumscan.org .

PMID- 20030400
TI  - Mechanisms by which human DNA primase chooses to polymerize a nucleoside
      triphosphate.
AB  - Human DNA primase synthesizes short RNA primers that DNA polymerase alpha then
      elongates during the initiation of all new DNA strands. Even though primase
      misincorporates NTPs at a relatively high frequency, this likely does not impact
      the final DNA product since the RNA primer is replaced with DNA. We used an
      extensive series of purine and pyrimidine analogues to provide further insights
      into the mechanism by which primase chooses whether or not to polymerize a NTP.
      Primase readily polymerized a size-expanded cytosine analogue, 1,3-diaza-2
      oxophenothiazine NTP, across from a templating G but not across from A. The
      enzyme did not efficiently polymerize NTPs incapable of forming two Watson-Crick
      hydrogen bonds with the templating base with the exception of UTP opposite purine
      deoxyribonucleoside. Likewise, primase did not generate base pairs between two
      nucleotides with altered Watson-Crick hydrogen-bonding patterns. Examining the
      mechanism of NTP polymerization revealed that human primase can misincorporate
      NTPs via both template misreading and a primer-template slippage mechanism.
      Together, these data demonstrate that human primase strongly depends on Watson
      Crick hydrogen bonds for efficient nucleotide polymerization, much more so than
      the mechanistically related herpes primase, and provide insights into the
      potential roles of primer-template stability and base tautomerization during
      misincorporation.

PMID- 20030401
TI  - Monitoring bioaugmenation with single-well push-pull tests in sediment systems
      contaminated with trichloroethene.
AB  - Bioaugmentation to enhance the rate and extent of reductive dechlorination of
      chlorinated ethenes was investigated in intermediate ( approximately 1 m) scale
      physical aquifer models (PAMs) designed to simulate the groundwater flow field
      near an injection well. Push-pull tests were used to quantify the reductive
      dechlorination of injected trichloroethene (TCE) and trichlorofluoroethene (TCFE)
      in prepared sediment packs with and without an added dechlorinating culture
      containing Dehalococcoides spp. Distribution of the added culture throughout the
      sediment pack was confirmed by microscopic observation. Repeated additions of TCE
      (100-350 microM) were completely transformed to ethene in 14 days and a
      subsequent TCFE addition (114 microM) was completely transformed to fluoroethene
      (FE) in 24 days. Similar transformation rates, product distributions, and time
      courses for TCE and TCFE transformation were observed when these compounds were
      added together at similar initial concentrations. In the control PAM
      (nonbioaugmented), TCE and TCFE were transformed to only cis-DCE and cis-DCFE,
      respectively, and transformation rates were 6-12 times slower than those in the
      bioaugmented PAM. The use of TCFE for push-pull tests is shown to be an effective
      tool for detecting and quantifying the effects of bioaugmentation on TCE
      transformation.

PMID- 20030402
TI  - Protocol to reconstruct historical contaminant loading to large lakes: the Lake
      Michigan sediment record of mercury.
AB  - Samples of opportunity from Pb-210 dated sediment cores collected from Lake
      Michigan between 1994 and 1996 were analyzed for mercury. The storage of
      anthropogenic and total (post-1850) mercury in the lake is calculated to be 186
      and 228 t, respectively. By setting the sum of mercury stored in a representative
      core equal to the mercury storage within the entire lake, the time variation of
      annual mercury loading to the lake is calculated. The modern (1980-2002) mercury
      flux to the lake represented by the surface of the core at the time of collection
      in 1994 was 21.4 microg/m(2)/y. The preindustrial flux (< or =1850) was 3.09
      microg/m(2)/y, and the peak flux in 1946 was 53.3 microg/m(2)/y. These yield
      modern and peak enrichment factors of 6.92 and 17.2, respectively. Modern fluxes
      exceed published atmospheric deposition estimates and, therefore, include
      terrestrial point sources, atmospheric deposition to watersheds, and atmospheric
      deposition to the lake. The modern net mercury load to the lake's sediments was
      1157 kg/y in 1994. The atmosphere is estimated to contribute 91% of this load
      directly to the lake.

PMID- 20030403
TI  - Antioxidant activities and xanthine oxidase inhibitory effects of phenolic
      phytochemicals from Acacia confusa twigs and branches.
AB  - This study investigates bioactivities and active phytochemicals of the extracts
      of twigs and branches from the indigenous Taiwanese tree Acacia confusa Merr. The
      bioassay-guided fractionation yielded 8 potent antioxidative phytochemicals.
      Catechins are the major components in the extract of 5 cm branch bark, including
      catechin, catechin-3-O-rhamnopyranoside, epi-catechin, and quercetin-3-O
      rhamnopyranoside, while flavonol glycosides are the major components in twig
      extract, namely, myricetin-3-O-glucopyranoside, myricetin-3-O-rhamnopyranoside,
      quercetin-3-O-rhamnopyranoside, myricetin-3-O-(2''-O-galloyl)-alpha
      rhamnopyranoside, and luteolin. Of the test compounds, myricetin-3-O-(2''-O
      galloyl)-alpha-rhamnopyranoside exhibited the highest antioxidant activity
      against DPPH radicals, showing a 2.8-fold lower IC(50) value of 5.3 microM
      related to that of quercetin. On the other hand, catechins apparently had no XOD
      inhibitory effect apart from their good antioxidant activities, while luteolin
      exhibited excellent activity against XOD with an IC(50) value of 11.6 microM.
      These results may provide useful information for future studies on the
      applications of A. confusa to be used as a source for natural health products.

PMID- 20030404
TI  - Cysteine sulfoxides and volatile sulfur compounds from Allium tripedale.
AB  - Allium tripedale Trautv. belonging to the subgenus Nectaroscordum grows naturally
      in the mountainous areas of northwest Iran. Leaves have a very strong and
      somewhat unpleasant taste and are widely used by the local population as a spicy
      vegetable. Three new cysteine based compounds were identified in A. tripedale as
      the first examples of sulfur containing 1-butenyl derivatives in nature. The
      compounds have been described as o-phthaldialdehyde (OPA) derivatives and
      identified as (+)-S-(1-butenyl)-L-cysteine sulfoxide (homoisoalliin) and its
      gamma-glutamyl derivative as well as the gamma-glutamyl derivative of S-(1
      butenyl)-L-cysteine (desoxyhomoisoalliin). These cysteine sulfoxides have been
      also found in Allium siculum Ucria. As volatile compounds, di-(1-butenyl)
      disulfide and the cepaene-like compounds di-(1-S-sulfoxymethyl-butyl)-disulfide,
      1-S-sulfoxymethyl-butyl-1'-S-sulfoxy-1-butenyl-butyl-disulfide and 1-S
      sulfoxymethyl-butyl-1'-S-sulfoxybutyl-butyl-disulfide could be tentatively
      identified by various MS experiments. Primary products resulting from the
      alliinase reaction of homoisoalliin seem to be highly unstable and were rapidly
      converted to the volatile compounds listed above.

PMID- 20030405
TI  - Benzo[e]isoindole-1,3-diones as potential inhibitors of glycogen synthase kinase
      3 (GSK-3). Synthesis, kinase inhibitory activity, zebrafish phenotype, and
      modeling of binding mode.
AB  - Benzo[e]isoindole-1,3-dione derivatives were synthesized, and the effects on GSK
      3beta activity and zebrafish embryo growth were evaluated. A series of
      derivatives show obvious inhibitory activity against GSK-3beta. The most potent
      inhibitor, 7,8-dimethoxy-5-methylbenzo[e]isoindole-1,3-dione (8a), shows
      nanomolar IC(50) and obvious phenotype on zebrafish embryo growth associated with
      the inhibition of GSK-3beta at low micromolar concentration. The interaction mode
      between 8a and GSK-3beta was characterized by computational modeling.

PMID- 20030406
TI  - Theoretical study of the mechanism of inhibition of xanthine oxidase by
      flavonoids and gallic acid derivatives.
AB  - Xanthine oxidase is a flavoprotein enzyme which catalyzes the oxidative
      hydroxylation of purine substrates. Because of its availability, it has become a
      model for structural molybdoenzymes in general. The enzyme is a well-established
      target of drugs against gout and hyperuricemia and exists in two forms: oxidase
      and deshydrogenase. In some pathologies, its level increases in oxidase form,
      being the source of free radicals which can cause damage to surrounding tissues.
      It is important to understand the mechanisms of the enzyme inhibition to help in
      the search of new inhibitors. The main active center is a molybdopterin buried in
      a cavity. Theoretical calculations can be of some help for distinguishing the
      important aspects in the inhibition: attraction inside the cavity and anchorage.
      In this paper, the molybdopterin molecule geometry has been optimized by ab
      initio with the DFT method and the results have been shown to be very similar to
      the X-ray coordinates. In order to evaluate the attraction inside the cavity, the
      electrostatic potential between the charged molybdopterin molecule and two series
      of inhibitors, some flavonoids, and some gallic acid derivatives have been
      calculated using the multipolar development supplied by the Gaussian package. The
      good concordance between the electrostatic force and IC(50) indicates that the
      attraction is an important factor in the inhibition and must be taken into
      account in the designing of new drugs.

PMID- 20030407
TI  - Site-specific chemistry directed by a bifunctional nanostructured surface.
AB  - Using the scanning tunneling microscope (STM), we have created a bifunctional
      nanostructured surface which consists of parallel stripes of gold atoms on the
      Au(111) substrate. Each stripe has two parallel step-edges separated by a few
      nanometers in distance. The two step-edges have very different binding properties
      to molecules, and they are able to separate C(60) molecules into two types of
      adsorbed structures, giving rise to a controlled formation of two-dimensional
      closely spaced multiple molecular nanostructures.

PMID- 20030408
TI  - Active-site engineering of benzaldehyde lyase shows that a point mutation can
      confer both new reactivity and susceptibility to mechanism-based inhibition.
AB  - Benzaldehyde lyase (BAL) from Pseudomonas putida is a thiamin diphosphate (ThDP)
      dependent enzyme that catalyzes the breakdown of (R)-benzoin. Here we report that
      a point mutant, BAL A28S, not only catalyzes the decarboxylation of
      benzoylformate but, like benzoylformate decarboxylase (BFDC), is also inactivated
      by the benzoylformate analogues methyl benzoylphosphonate (MBP) and
      benzoylphosphonate (BP). The latter has no effect on wild-type BAL, and the
      inactivation of the A28S variant is shown to result from phosphorylation of the
      newly introduced serine residue. This lends support to the proposal that an
      appropriately placed nucleophile facilitates the expulsion of carbon dioxide from
      the active site in many ThDP-dependent decarboxylases.

PMID- 20030409
TI  - Dammarane-type saponins from the flower buds of Panax ginseng and their
      intracellular radical scavenging capacity.
AB  - Korean ginseng (Panax ginseng C.A. Meyer) has been extensively used as a
      functional food for thousands of years. This study with the aim to evaluate the
      potential of P. ginseng flower components as a functional food with medicinal
      properties resulted in the identification of three new dammarane-type saponins,
      named floralginsenosides Ka-Kc (1-3), along with seventeen known ones (4-20).
      Their structures were elucidated on the basis of chemical and spectroscopic
      methods, and their antioxidant activities were evaluated by the intracellular ROS
      radical scavenging DCF-DA assay. Among them, floralginsenoside Ka (1) displayed
      potent scavenging activity with the inhibition value of 64% at 10 microM; and
      ginsenoside Rb(1) (13), floralginsenoside Kc (3), floralginsenoside Kb (2),
      vinaginsenoside R(9) (11), majoroside F(1) (12), ginsenoside I (17), and
      ginsenoside II (18) showed moderate scavenging capacity with the inhibition rate
      of 28, 33, 35, 35, 35, 38, and 38% at 10 microM, respectively. These results
      warrant further studies concerning the potential of saponin extracts of P.
      ginseng flowers for functional foods.

PMID- 20030411
TI  - Formation of N(epsilon)-(carboxymethyl)lysine and loss of lysine in casein
      glucose-fatty acid model systems.
AB  - Advanced glycation end-products (AGEs) and advanced lipoxidation end-products
      (ALEs) form when proteins are heated with reducing sugar or lipid. N(epsilon)
      (Carboxymethyl)lysine (CML) is the most commonly studied AGE/ALE in foods, but
      the relative importance of dietary sugar and lipid as its precursors is
      uncertain. The aim of this study was to determine the relative amounts of CML
      formed from fatty acid and glucose in a model food system. Model systems were
      prepared by heating casein (3.2%) with glucose or fatty acid (oleic, linoleic,
      linolenic, or arachidonic acid) (200 mM) or a mixture of glucose and linolenic
      acid (200 mM of each precursor) at 95 degrees C for up to 8 h. CML was determined
      by ultrapressure liquid chromatography-tandem mass spectrometry. The amount of
      CML formed from casein and glucose incubated at 95 degrees C for 8 h was 15-fold
      higher than that obtained when casein was heated with arachidonic acid under the
      same conditions. However, the loss of lysine in the casein-arachidonic acid
      incubations was 83% compared to 54% loss in the casein-glucose incubations. The
      loss of lysine in casein-fatty acid model systems increased with degree of
      unsaturation of the fatty acid. The formation of lipid peroxidation products
      during oxidation of fatty acids might be a potent factor for loss of lysine in
      the casein-fatty acid systems.

PMID- 20030413
TI  - Controlled nitric oxide delivery platform based on S-nitrosothiol conjugated
      interpolymer complexes for diabetic wound healing.
AB  - Nitric oxide (NO) is known to play a critical role in enhancing wound healing as
      topical NO administration has demonstrated enhanced wound healing in diabetic
      animal models. However, this approach has been limited by the short duration of
      NO release, short half-life of NO, and instability of available NO donors. To
      overcome these deficiencies, we have developed a new NO delivery platform based
      on grafting S-nitrosothiols (RSNOs), derived from endogenous glutathione (GSH) or
      its oligomeric derivatives, phytochelatins (PCs), onto poly(vinyl methyl ether-co
      maleic anhydride) (PVMMA), and their subsequent formation of interpolymer
      complexes with poly(vinyl pyrrolidone) (PVP). Such interpolymer complexes provide
      controlled release of NO for an extended duration (>10 days) and exhibit enhanced
      stability in the solid state over that of free RSNOs. The existence of
      intermolecular hydrogen bonding in such complexes and the formation of disulfide
      bonds following the NO release have been confirmed by FTIR and Raman. Preliminary
      wound healing study in a diabetic rat model demonstrates that, with a single
      topical application, the present controlled release NO delivery system can
      effectively accelerate wound closure as compared with the control (p < 0.05). The
      results suggest that the present NO releasing interpolymer complexes could be
      potentially useful for diabetic wound healing.

PMID- 20030412
TI  - Chronic exposure to zinc chromate induces centrosome amplification and spindle
      assembly checkpoint bypass in human lung fibroblasts.
AB  - Hexavalent chromium (Cr(VI)) compounds are known human lung carcinogens.
      Solubility plays an important role in its carcinogenicity with the particulate or
      insoluble form being the most potent. Of the particulate Cr(VI) compounds, zinc
      chromate appears to be the most potent carcinogen; however, very few studies have
      investigated its carcinogenic mechanism. In this study, we investigated the
      ability of chronic exposure to zinc chromate to induce numerical chromosome
      instability. We found no increase in aneuploidy after a 24 h exposure to zinc
      chromate, but with more chronic exposures, zinc chromate induced concentration-
      and time-dependent increases in aneuploidy in the form of hypodiploidy,
      hyperdiploidy, and tetraploidy. Zinc chromate also induced centrosome
      amplification in a concentration- and time-dependent manner in both interphase
      and mitotic cells after chronic exposure, producing cells with centriolar
      defects. Furthermore, chronic exposure to zinc chromate induced concentration-
      and time-dependent increases in spindle assembly checkpoint bypass with increases
      in centromere spreading, premature centromere division, and premature anaphase.
      Last, we found that chronic exposure to zinc chromate induced a G2 arrest. All
      together, these data indicate that zinc chromate can induce chromosome
      instability after prolonged exposures.

PMID- 20030414
TI  - Sceptrin, a marine natural compound, inhibits cell motility in a variety of
      cancer cell lines.
AB  - Sceptrin, a natural compound produced by various marine sponges, was tested for
      its effect on cell motility. We report for the first time that sceptrin inhibits
      cell motility in several cancer cell lines. The compound shows no toxicity at
      concentrations that are double the amount of sceptrin required for maximal
      inhibitory effect. Both random and factor-induced migration were impaired,
      suggesting that sceptrin targets a central process of cell motility machinery.
      Activity of de novo synthesized sceptrin was indistinguishable from sceptrin
      purified from Agelas nakamurai, and the inhibitory activity was found to be, at
      least partially, due to sceptrin's capability to inhibit cell contractility.
      Additionally, sceptrin was found to bind to monomeric actin, further suggesting a
      mechanism involving the actin cytoskeleton. Close analogues of sceptrin were
      synthesized, tested for their effect on cell motility, and found to be either
      equimolar or less potent compared to the parental compound. Inadvertent cell
      motility is a key contributing factor in various human diseases, including cancer
      and chronic inflammation. Marine compounds isolated from sponges have been proven
      to be an excellent source of metabolites that show biological activities. Given
      the recently achieved total synthesis of sceptrin in multigram quantities,
      sceptrin could prove to be an attractive lead molecule for further preclinical
      testing and development for therapeutic purposes, as well as a useful research
      tool to elucidate the mechanisms involved in cell motility.

PMID- 20030415
TI  - Role of brain-derived neurotrophic factor in the aetiology of depression:
      implications for pharmacological treatment.
AB  - Brain-derived neurotrophic factor (BDNF) is a critical mediator of activity
      dependent neuronal plasticity in the cerebral cortex. Deficits in neurotrophic
      factors have been proposed to underlie mood disorders. However, recent evidence
      suggests that mood disorders may be produced by abnormalities in the adaptation
      of neural networks to environmental conditions. Antidepressants may act by
      enhancing neuronal plasticity, which allows environmental inputs to modify the
      neuronal networks to better fine tune the individual to the outside world. Recent
      observations in the visual cortex directly support this idea. According to the
      network hypothesis of depression, changes in the levels of neurotrophins
      including BDNF may not directly produce depression or an antidepressant effect,
      but neurotrophins may act as critical tools in the process whereby environmental
      conditions guide neuronal networks to better adapt to the environment. This
      hypothesis suggests that antidepressant drugs should not be used alone but should
      always be combined with rehabilitation to guide the plastic networks within the
      brain.

PMID- 20030416
TI  - Progress in defining optimal treatment outcome in schizophrenia.
AB  - Historically, schizophrenia has been associated with early-onset, persistent
      symptoms, and progressive decline accompanied by poor functional recovery. The
      advent of effective drugs in the 1950s improved symptom control, at least from
      the standpoint of positive features (e.g. hallucinations, delusions). However,
      even here the response was limited and efficacy in other symptom domains
      (cognitive, deficit/negative) was minimal. With clozapine as the prototype, the
      second-generation antipsychotics arrived in the 1990s with claims of improved
      tolerability, as well as greater and broader clinical efficacy, all of which was
      to translate to gains in functional outcome and quality of life. The capacity of
      these drugs to effect such changes has since been tempered, but it remains that
      the research and hope generated served as an impetus to redefine outcomes. A
      medical-based model, centred on pharmacotherapy and symptom resolution, has given
      way to a re-conceptualization of schizophrenia and treatment goals. There is a
      clearer distinction between clinical and functional outcomes, and, with this,
      greater attention has been given to these other symptom domains that curtail
      improvement in the latter. At the same time, a concerted shift to shared decision
      making has underscored quality-of-life issues that benefit from, but cannot be
      guaranteed by, either clinical or functional improvement. To this end, the field
      has now embraced a recovery model that is seen as a process, multidimensional and
      individualized, rather than dichotomous and symptom driven.

PMID- 20030417
TI  - Role of antiepileptic drugs as preventive agents for migraine.
AB  - Migraine is a common neurological disease affecting about 12% of the population
      in Western Europe and North America, and causing a considerable burden both to
      migraineurs and to society. Severe, frequent and disabling migraine attacks, as
      well as those poorly responsive to acute care medication, require preventive
      treatment, which is often under-utilized. Antiepileptic drugs are used in the
      prevention of migraine. We performed a literature search of PubMed through June
      2008 for controlled trials of antiepileptic drugs in the prevention of migraine.
      The search identified 70 papers for a full-text review. The majority of these
      papers referred to valproate and topiramate, and showed that these drugs are
      effective and well tolerated in migraine prevention and are suitable for first
      line clinical use. On the other hand, acetazolamide, lamotrigine, oxcarbazepine
      and vigabatrin have been shown to be not effective and gabapentin requires
      further evaluation. For the rest of the antiepileptic drugs, no data from
      controlled trials are available.

PMID- 20030418
TI  - Safety reporting and adverse-event profile of mirtazapine described in randomized
      controlled trials in comparison with other classes of antidepressants in the
      acute-phase treatment of adults with depression: systematic review and meta
      analysis.
AB  - BACKGROUND: Mirtazapine has a unique mechanism of antidepressant action, and thus
      is thought to have a different profile of adverse events from that of other
      antidepressants. OBJECTIVE: To present a methodologically rigorous systematic
      review of the adverse event profile of mirtazapine and point to possible problems
      with safety reporting in randomized controlled trials (RCTs) of the acute-phase
      treatment of major depression in adults with mirtazapine in comparison with other
      types of antidepressant. METHODS: The Cochrane Collaboration Depression, Anxiety
      and Neurosis Controlled Trials Register was electronically searched using the
      following search terms: 'depress*', 'dysthymi*', 'adjustment disorder*', 'mood
      disorder*', 'affective disorder', 'affective symptoms' and 'mirtazapine'.
      Pharmaceutical companies and experts in this field were contacted, and the
      reference lists of the relevant RCTs were checked, for additional data. No
      language restriction was imposed. Two authors independently assessed the quality
      of trials for inclusion in the review. Disagreements were resolved by consensus.
      Two authors independently extracted data on adverse events. Disagreements were
      resolved by consensus. The adequacy of safety reporting was assessed by one
      author. Regarding the adequacy of safety reporting, the qualitative and
      quantitative parameters of safety reporting were determined. Regression analyses
      were conducted to assess characteristics of trials influencing safety reporting.
      The primary and secondary outcomes in the systematic review of the adverse events
      associated with mirtazapine were defined as the proportion of patients having
      each of 43 adverse events listed in the modified version of the WHO Adverse
      Reaction Terminology, and the proportion of patients experiencing at least one
      adverse event, respectively. Meta-analyses were conducted for these outcomes.
      RESULTS: Twenty-five RCTs involving 4842 patients were identified as meeting our
      inclusion criteria. With regard to safety reporting, only two trials and no
      trials were rated as 'adequate' in terms of the reporting of clinical adverse
      events and laboratory-determined toxicity, respectively. The proportion of text
      in the results sections of the study reports devoted to safety reporting was a
      mean of 22%. No associations were observed between the adequacy of safety
      reporting and any characteristics of the trials; however, sample size over 100
      participants in total and over 50 subjects in a study arm, double blindness and
      sponsorship by the company marketing mirtazapine were significantly associated
      with a greater number of reported adverse events in mirtazapine recipients. In
      terms of individual adverse events, mirtazapine was significantly less likely to
      cause hypertension or tachycardia (risk ratio [RR] 0.51) and tremor (RR 0.43)
      than tricyclic antidepressants (TCAs). In comparison with selective serotonin
      uptake inhibitors (SSRIs), mirtazapine was significantly more likely to cause
      weight gain or increased appetite (RR 3.68), increased salivation (RR 3.66),
      somnolence (RR 1.62) and fatigue (RR 1.45), but less likely to cause flatulence
      (RR 0.26), sweating (RR 0.28), sexual dysfunction (RR 0.34), tremor (RR 0.37),
      nausea or vomiting (RR 0.40), sleep disturbance (RR 0.55) and diarrhoea (RR
      0.61). In comparison with the serotonin-noradrenaline (norepinephrine) reuptake
      inhibitor (SNRI) venlafaxine, mirtazapine was significantly more likely to cause
      fatigue (RR 2.02), but less likely to cause sleep disturbance (RR 0.03), sweating
      (RR 0.03) and constipation (RR 0.25). Relative to trazodone, mirtazapine was
      significantly more likely to cause weight gain or increased appetite (RR 4.00).
      Approximately 70% of patients treated with mirtazapine experienced at least one
      adverse event, with no significant difference in comparison with other
      antidepressants. CONCLUSIONS: The study confirmed the paucity of adequate safety
      reporting in trials comparing mirtazapine with other types of antidepressant in
      the acute-phase treatment of depression in adults. Based on the available
      evidence, mirtazapine appears to have a unique adverse-event profile. Using these
      findings, clinicians can inform their patients, not only of the simple frequency
      of adverse events with mirtazapine, but also of the relative difference in the
      frequency of adverse events in comparison with that of other antidepressants, to
      aid pragmatic clinical decisions.

PMID- 20030419
TI  - Factors associated with serious adverse reactions to cholinesterase inhibitors: a
      study of spontaneous reporting.
AB  - BACKGROUND: Cholinesterase inhibitors are used in Alzheimer's disease, mostly in
      elderly persons with co-morbidities and receiving co-medications that could
      increase the risk of serious adverse reactions. OBJECTIVE: To identify factors
      associated with serious adverse drug reactions (ADRs) in patients treated with
      cholinesterase inhibitors. METHODS: All ADRs associated with donepezil,
      rivastigmine or galantamine were identified in the French pharmacovigilance
      database, from the launching of these drugs to January 2007. Serious ADRs (SADRs)
      were those that led to death, hospitalization or prolongation of hospitalization,
      or that were life threatening. A multiple logistic regression analysis was used
      to identify factors associated with seriousness in the reported adverse
      reactions. RESULTS: We identified 773 reports of ADRs related to cholinesterase
      inhibitor use, among which 438 (57%) concerned SADRs. The median age of patients
      was 80 years (interquartile range: 75-84 years); 65.1% were women. The most
      represented ADRs were those responsible for CNS disorders (17.0%),
      gastrointestinal disorders (16.2%) and cardiac rhythm disorders (11.2%). Factors
      associated with an increased risk of SADRs were: age (odds ratio [OR] 1.92; 95%
      CI 1.22, 3.02 for subjects aged 85 years and over), use of atypical
      antipsychotics (OR 2.15; 95% CI 1.04, 4.46), use of conventional antipsychotics
      (OR 2.06, 95% CI 1.10, 3.85), use of antihypertensive drugs (OR 2.11; 95% CI
      1.47, 3.02) and use of drugs targeting the alimentary tract and metabolism (OR
      1.62; 95% CI 1.06, 2.46). The use of benzodiazepines (long-acting or others),
      antidepressants (tricyclic or others) or antiarrhythmic drugs was not associated
      with the reporting of SADRs. CONCLUSIONS: An increased risk of SADRs related to
      cholinesterase inhibitors was associated with the use of antipsychotics (with no
      difference between conventional and atypical antipsychotics), drugs targeting the
      alimentary tract/metabolism and antihypertensive drugs. It was not associated
      with the use of other psychotropic drugs, other non-psychotropic CNS drugs or
      with the use of antiarrhythmic agents. The association with drugs targeting the
      alimentary tract and metabolism could result from a protopathic bias or reflect
      the particular sensitivity to serious nausea and vomiting in patients already
      treated for gastrointestinal disorders. These results confirm that attention
      needs to be paid to patients receiving both cholinesterase inhibitors and
      antipsychotics.

PMID- 20030420
TI  - Blonanserin: a review of its use in the management of schizophrenia.
AB  - Oral blonanserin (Lonasen) is an atypical antipsychotic agent indicated for use
      in patients with schizophrenia in Japan and Korea. It is effective in the
      treatment of patients with schizophrenia, providing short- and long-term efficacy
      against both the positive and negative symptoms of the disorder in several
      randomized and noncomparative trials. Notably, in two randomized, double-blind
      trials of 8 weeks' duration, blonanserin was noninferior to haloperidol or
      risperidone for primary endpoints, although it appeared to be better than
      haloperidol in improving negative symptoms. Blonanserin is generally well
      tolerated and appears to have an acceptable profile in terms of bodyweight gain.
      Potential tolerability benefits of the drug in short-term trials included fewer
      extrapyramidal symptoms than haloperidol and fewer reports of prolactin level
      increases or hyperprolactinaemia than risperidone. Nevertheless, extrapyramidal
      symptoms and hyperprolactinaemia were among the most common adverse reactions
      associated with blonanserin in noncomparative long-term studies. Further
      prospective and long-term comparative studies are required in order to
      definitively position blonanserin with respect to other antipsychotic agents. In
      the meantime, available clinical data suggest that blonanserin is an effective
      and generally well tolerated option for the short-term treatment of schizophrenia
      and for those requiring longer-term therapy.

PMID- 20030421
TI  - Spotlight on atomoxetine in attention-deficit hyperactivity disorder in children
      and adolescents.
AB  - Atomoxetine (Strattera) is a selective noradrenaline (norepinephrine) reuptake
      inhibitor that is not classified as a stimulant, and is indicated for use in
      patients with attention-deficit hyperactivity disorder (ADHD). Atomoxetine is
      effective and generally well tolerated. It is significantly more effective than
      placebo and standard current therapy and does not differ significantly from, or
      is noninferior to, immediate-release methylphenidate; however, it is
      significantly less effective than the extended-release methylphenidate
      formulation OROS methylphenidate (hereafter referred to as osmotically released
      methylphenidate) and extended-release mixed amfetamine salts. Atomoxetine can be
      administered either as a single daily dose or split into two evenly divided
      doses, has a negligible risk of abuse or misuse and is not a controlled substance
      in the US. Atomoxetine is particularly useful for patients at risk of substance
      abuse, as well as those who have co-morbid anxiety or tics, or who do not wish to
      take a controlled substance. Thus, atomoxetine is a useful option in the
      treatment of ADHD in children and adolescents.

PMID- 20030422
TI  - Pharmacological treatment of fibromyalgia syndrome: new developments.
AB  - Fibromyalgia is a chronic pain disorder characterized by widespread pain,
      stiffness, insomnia, fatigue and distress. Several randomized controlled trials
      (RCTs) have shown moderate effectiveness of pharmacological therapies for
      fibromyalgia pain. Evidence from these trials suggests that pharmacological
      therapy can not only improve pain but also fatigue, function and well-being in
      patients with fibromyalgia. Duloxetine and milnacipran, two highly selective
      serotonin-norepinephrine (noradrenaline) reuptake inhibitors, and the
      alpha(2)delta agonist pregabalin have been approved by the US FDA for the
      treatment of fibromyalgia symptoms. In general, about half of all treated
      patients seem to experience a 30% reduction of symptoms, suggesting that many
      patients with fibromyalgia will require additional therapies. Thus, other forms
      of treatment, including exercise, cognitive behavioural therapies and self
      management strategies, may be necessary to achieve satisfactory treatment
      outcomes. Despite promising results of pilot trials, RCTs with dopamine receptor
      agonists and sodium channel antagonists have so far been disappointing for
      patients with fibromyalgia. However, new pharmacological approaches for the
      treatment of fibromyalgia pain and insomnia using sodium oxybate appear to be
      promising.

PMID- 20030423
TI  - Attention-deficit hyperactivity disorder: recent advances in paediatric
      pharmacotherapy.
AB  - Throughout this decade, there has been significant research into
      pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This
      article considers the efficacy and safety of five of the more novel long-acting
      pharmacological treatments recently approved by the FDA for marketing in the US
      for paediatric ADHD, along with an alpha(2)-adrenoceptor agonist in preparation.
      Reviewed treatments include the non-stimulant atomoxetine, three novel extended
      release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine
      dimesylate and the methylphenidate transdermal system (TDS), and the recently
      approved XR alpha(2)-adrenoceptor agonist, guanfacine. Dexmethylphenidate XR is a
      stimulant treatment in a single isomer form, and has an efficacy and tolerability
      similar to two doses of immediate-release (IR) dexmethylphenidate when taken 4
      hours apart, but is dosed at half of the usual d,l-methylphenidate dose.
      Dexmethylphenidate XR utilizes a beaded bimodal release, with 50% initially
      released and another 50% released 4 hours later to provide benefit lasting up to
      10-12 hours. Lisdexamfetamine was the first stimulant treatment approved as a
      prodrug, whereby the single isomer d-amfetamine remains pharmacologically
      inactive until activated by cleaving the lysine. Its efficacy and tolerability
      are generally consistent with that of XR mixed amfetamine salts, with this
      activation method and more consistent absorption generally resulting in up to an
      11- to 13-hour benefit. The methylphenidate TDS patch utilizes skin absorption to
      provide predictable and uniform delivery of methylphenidate when worn for 9
      hours/day. The efficacy and tolerability of the methylphenidate TDS patch is
      generally consistent with that of osmotic-controlled release oral system (OROS)
      methylphenidate, providing benefit for about 11-12 hours. Because of their
      formulation, lisdexamfetamine and methylphenidate each have an onset of effect at
      about 2 hours after administration. An adjustable wear time for the
      methylphenidate TDS patch accommodates related adverse effects, but its
      disadvantages are frequent skin irritation and the need to remember to take the
      patch off. Atomoxetine is the first non-stimulant treatment approved by the FDA
      and employs weight-based dosing up to 1.4 mg/kg/day. Benefit is generally
      observed within 2-8 weeks of initiation and is considered to have a lesser
      therapeutic effect than that of stimulants. A recent parallel-group controlled
      study found that atomoxetine (up to 1.8 mg/kg/day) and OROS methylphenidate both
      improved ADHD symptoms, although subjects receiving OROS methylphenidate had a
      significantly better response. Interestingly, treatment-naive children had a
      similar beneficial response to atomoxetine as those receiving OROS
      methylphenidate. Subsequent crossover treatment revealed a subgroup of youths who
      did not respond well to OROS methylphenidate but did respond to atomoxetine. Also
      identified was a larger than expected subgroup who did not respond well to either
      active treatment, confirming the need to continue the pursuit of novel
      treatments. As of September of 2009, guanfacine in XR form is the first alpha(2)
      adrenoceptor agonist to gain approval to treat ADHD, approved for the treatment
      of 6- to 17-year olds. A second alpha(2)-adrenoceptor agonist, clonidine, is in
      development as a potential XR treatment for paediatric ADHD. IR clonidine has a
      fast onset and short half-life, with its use historically limited by somnolence.
      Although early formulations did not improve inattention well, recent evidence
      suggests that clonidine XR may have potential use as monotherapy or in extending
      benefit when taken with a stimulant. Guanfacine has a more specific neuronal
      action and a longer action than that of clonidine. The approved dosing of
      guanfacine XR 1 to 4 mg daily generally provides symptom benefit lasting 8-14
      hours, and up to 24 hours in some children and adolescents receiving a higher
      dose. Such recent developments and ongoing study of additional potential
      pharmacological interventions may lead to additional future treatment options for
      children with ADHD.

PMID- 20030424
TI  - Nebivolol: haemodynamic effects and clinical significance of combined beta
      blockade and nitric oxide release.
AB  - Nebivolol is a third-generation beta-adrenergic receptor antagonist (beta
      blocker) with high selectivity for beta(1)-adrenergic receptors. In addition, it
      causes vasodilatation via interaction with the endothelial L-arginine/nitric
      oxide (NO) pathway. This dual mechanism of action underlies many of the
      haemodynamic properties of nebivolol, which include reductions in heart rate and
      blood pressure (BP), and improvements in systolic and diastolic function. With
      respect to BP lowering, the NO-mediated effects cause a reduction in peripheral
      vascular resistance and an increase in stroke volume with preservation of cardiac
      output. Flow-mediated dilatation and coronary flow reserve are also increased
      during nebivolol administration. Other haemodynamic effects include beneficial
      effects on pulmonary artery pressure, pulmonary wedge pressure, exercise capacity
      and left ventricular ejection fraction. In addition, nebivolol does not appear to
      have adverse effects on lipid metabolism and insulin sensitivity like traditional
      beta-blockers. The documented beneficial haemodynamic effects of nebivolol are
      translated into improved clinical outcomes in patients with hypertension or heart
      failure. In patients with hypertension, the incidence of bradycardia with
      nebivolol is often lower than that with other currently available beta-blockers.
      This, along with peripheral vasodilatation and NO-induced benefits such as
      antioxidant activity and reversal of endothelial dysfunction, should facilitate
      better protection from cardiovascular events. In addition, nebivolol has shown an
      improved tolerability profile, particularly with respect to events commonly
      associated with beta-blockers, such as fatigue and sexual dysfunction. Data from
      SENIORS (Study of the Effects of Nebivolol Intervention on Outcomes and
      Rehospitalization in Seniors with Heart Failure) showed that significantly fewer
      nebivolol versus placebo recipients experienced the primary endpoint of all-cause
      mortality or cardiovascular hospitalization. The benefits of nebivolol therapy
      were shown to be cost effective. Thus, nebivolol is an effective and well
      tolerated agent with benefits over and above those of traditional beta-blockade
      because of its effects on NO release, which give it unique haemodynamic effects,
      cardioprotective activity and a good tolerability profile.

PMID- 20030426
TI  - Icatibant.
AB  - Icatibant is a selective antagonist of the bradykinin type 2 receptor. In the
      randomized, double-blind, multicentre, FAST-1 trial, the difference in the median
      time to the onset of symptom relief (primary endpoint) did not reach statistical
      significance between a single dose of subcutaneous icatibant 30 mg and placebo in
      adults with moderate to very severe acute abdominal or cutaneous episodes of
      hereditary angioedema. However, icatibant was effective with regard to several
      other endpoints, providing significantly greater reductions from baseline in
      symptom severity scores 4 and 12 hours after administration, and eliciting
      significantly shorter times to both first symptom improvement and overall patient
      improvement than placebo. In the similarly designed, active comparator
      controlled, FAST-2 trial, a single dose of subcutaneous icatibant 30 mg was
      associated with a significantly shorter median time to onset of symptom relief
      (primary endpoint) than oral tranexamic acid in adults with acute abdominal or
      cutaneous episodes of hereditary angioedema, and was also more effective than
      tranexamic acid in terms of most other endpoints. Across both FAST-1 and -2, the
      efficacy of subcutaneous icatibant 30 mg in the treatment of laryngeal episodes
      of hereditary angioedema was generally consistent with that seen for abdominal
      and cutaneous episodes, with a median time to first symptom improvement of 0.6
      1.0 hours. Subcutaneous icatibant was generally well tolerated in adult patients
      with hereditary angioedema in the FAST trials, with the most common adverse
      events being injection-site reactions that were generally of mild severity,
      transient in nature and resolved spontaneously without treatment.

PMID- 20030425
TI  - Formulations of fentanyl for the management of pain.
AB  - Fentanyl is an opioid initially developed for parenteral administration. While
      oral administration is not an option due to a high first-pass metabolism, its
      high potency and lipophilicity have made a number of new routes of administration
      feasible. The transdermal therapeutic system offers an excellent option for long
      term treatment of cancer and chronic pain, achieving stable plasma concentrations
      over the treatment period. The recent change from reservoir to matrix systems has
      made these systems more convenient to wear and safer to use, while being
      bioequivalent. In contrast, the patient-controlled iontophoretic transdermal
      system has been developed to enable on-demand delivery of transdermal bolus doses
      of fentanyl to treat postoperative pain. It offers a needle-free system to
      provide patient-controlled analgesia otherwise offered by intravenous pumps.
      However, due to technical difficulties the system is currently not clinically
      available. Oral transmucosal fentanyl utilizes the rapid uptake through the
      buccal mucosa to achieve high plasma concentrations rapidly and is indicated to
      treat breakthrough pain in patients who are not opioid-naive. The recently
      introduced fentanyl buccal tablets offer slightly better pharmacokinetics for the
      same indication. The intranasal route is another option to achieve rapid uptake
      of fentanyl, and is currently being investigated to provide acute and
      breakthrough pain relief. Transpulmonary administration of fentanyl remains
      experimental and this route of administration is not yet in clinical use.
      Overall, the specific pharmacological and physicochemical properties of fentanyl
      have made this compound highly suitable for novel routes of administration in a
      range of clinical indications.

PMID- 20030427
TI  - Besifloxacin ophthalmic suspension 0.6%.
AB  - Besifloxacin is a novel fluoroquinolone that, like other fluoroquinolones, acts
      by inhibiting the essential bacterial enzymes DNA gyrase and topoisomerase IV.
      Topical besifloxacin ophthalmic suspension 0.6% is indicated for use in patients
      with bacterial conjunctivitis caused by susceptible bacteria. Besifloxacin had in
      vitro activity against a broad spectrum of Gram-positive and -negative bacteria
      that commonly cause ocular infections (e.g. Haemophilus influenzae,
      Staphylococcus aureus, S. epidermidis and Streptococcus pneumoniae), including
      drug-resistant strains. In two randomized, double-blind, multicentre trials,
      besifloxacin ophthalmic suspension 0.6% administered at the recommended dose for
      5 days in patients aged > or =1 year with bacterial conjunctivitis was
      significantly (p < 0.01) more effective than vehicle in terms of clinical
      resolution and microbial eradication rates (coprimary endpoints) at study visit
      two (day 5+/-1) or three (day 8 or 9) [primary timepoints]. Besifloxacin
      ophthalmic suspension 0.6% was noninferior to moxifloxacin ophthalmic solution
      0.5% in patients aged > or =1 year with bacterial conjunctivitis with regard to
      clinical resolution (58.3% vs 59.4%) and microbial eradication (93.3% vs 91.1%)
      rates on day 5 +/- 1 of treatment (coprimary endpoints) in a randomized, double
      blind, multicentre trial; both drugs were administered at a dosage of one drop in
      the affected eye(s) three times daily for 5 days. Besifloxacin ophthalmic
      suspension 0.6% was generally well tolerated in clinical trials, with most
      adverse events being mild in severity. The tolerability profile of besifloxacin
      ophthalmic suspension 0.6% was similar to that of moxifloxacin ophthalmic
      solution 0.5%.

PMID- 20030428
TI  - Milnacipran: in fibromyalgia.
AB  - Milnacipran is an orally administered selective serotonin and norepinephrine
      (noradrenaline) reuptake inhibitor indicated for the management of fibromyalgia
      in adults. In adults, milnacipran was generally effective in the treatment of
      fibromyalgia in four well designed trials of 3 or 6 months' duration. Composite
      responder rates for the treatment of fibromyalgia and fibromyalgia pain (co
      primary efficacy variables) were generally higher with milnacipran 100 or 200
      mg/day (in two divided doses) than with placebo after 12 weeks of fixed-dose
      treatment. In one study, the composite responder rate for fibromyalgia pain (co
      primary efficacy variable) was also higher with milnacipran 200 mg/day than with
      placebo after 24 weeks of fixed-dose treatment. Furthermore, the benefits of
      milnacipran therapy were sustained in a 6-month extension of an initial double
      blind trial. Improvements from baseline in mean 24-hour recall pain scores, mean
      weekly recall pain scores, Patient Global Impression of Change scores and in
      several items of the Fibromyalgia Impact Questionnaire were observed in patients
      receiving continuous milnacipran for up to 12 months, as well as in patients who
      switched from placebo to milnacipran therapy at the start of the extension phase.
      Milnacipran was generally well tolerated in adults with fibromyalgia, with most
      adverse events being mild to moderate in severity. Nausea was the most common
      adverse event reported in milnacipran recipients.

PMID- 20030429
TI  - Autoimmune bullous dermatoses in the elderly: an update on pathophysiology,
      diagnosis and management.
AB  - Elderly individuals are susceptible to autoimmune bullous dermatoses (ABDs),
      which may be associated with high morbidity and mortality. ABDs result from an
      autoimmune response to components of the basement membrane zone at the dermal
      epidermal junction or desmosomes. Bullous pemphigoid results from autoimmunity to
      hemidesmosomal proteins present in the basement membrane of stratified squamous
      epithelia. Patients present with tense blisters in flexural areas of the skin.
      Mild disease may be treated with potent topical corticosteroids, while extensive
      disease usually requires systemic corticosteroids or systemic immunosuppressive
      agents such as azathioprine. Mucosal pemphigoid affects one or more mucous
      membranes that are lined by stratified squamous epithelia. The two most commonly
      involved sites are the eye and the oral cavity. Lesions frequently result in scar
      formation that may cause blindness. Patients with severe disease or ocular
      involvement require aggressive therapy with corticosteroids and cyclophosphamide.
      Epidermolysis bullosa acquisita results from autoimmunity to type VII collagen in
      the anchoring fibrils of the basement membrane. Lesions may either arise on an
      inflammatory base or be non-inflammatory and result primarily from trauma.
      Treatment options include corticosteroids, dapsone, ciclosporin, methotrexate and
      plasmapheresis/immunoapheresis. Paraneoplastic pemphigus results from
      autoimmunity to multiple desmosomal antigens. The disorder is associated with
      neoplasms, especially leukaemia, lymphoma and thymoma. Patients present with
      stomatitis and polymorphous skin eruption. The disease may respond to successful
      treatment of the underlying neoplasm or may require immunosuppressive therapy.

PMID- 20030431
TI  - Reasons for undertreatment with oral anticoagulants in frail geriatric
      outpatients with atrial fibrillation: a prospective, descriptive study.
AB  - OBJECTIVES: The main aims of the study were to explore whether oral
      anticoagulation (OAC) for atrial fibrillation (AF) in geriatric outpatients is
      prescribed in accordance with international (American College of
      Cardiology/American Heart Association/European Society of Cardiology
      [ACC/AHA/ESC]) and Dutch national guidelines for the general practitioner (GP)
      and to identify whether age and selected co-morbid conditions are associated with
      undertreatment. As a secondary objective, we wanted to establish how many
      patients discontinue OAC because of major bleeding. METHODS: In 2004, at the
      first visit of all patients to the geriatric day clinic of the Slotervaart
      Hospital in Amsterdam, the Netherlands, demographic data, Mini-Mental State
      Examination score, medical history, Charlson Comorbidity Index score, and data on
      medication use and changes were documented. The presence of AF was established by
      assessment of medical history information obtained by the GP, the history taken
      from patients and their caregivers, and the results of clinical evaluation,
      including ECG findings. Associations between the use of OAC, demographic data and
      co-morbid conditions registered in the Dutch NHG (Nederlands Huisartsen
      Genootschap [Dutch College of General Practitioners]) standard for GPs as risk
      factors for stroke or contraindications to the use of OAC were analysed. The
      reasons for discontinuing OAC were assessed after 4 years by requesting the
      information from the anticoagulation services or the GP. RESULTS: At the time of
      the initial visit, 17.5% of the 807 outpatients had chronic AF (n = 135) or were
      known to have paroxysmal AF (n = 6). The mean age of the 141 patients in this
      cohort was 84.3 years (SD 6.2 years). Co-morbid conditions increasing the risk of
      stroke were present in 129 patients (91.5%). Contraindications to the use of OAC
      were observed in 118 patients (83.7%). Of the 116 patients with AF in their
      history before their visit, 57.8% were being treated with OAC at the time of
      their visit. After comprehensive geriatric assessment, 73 (51.8%) of the 141
      patients with chronic or paroxysmal AF were continued on OAC. Of the 141 patients
      with chronic or paroxysmal AF, 110 (78.0%) had both extra stroke risk factors and
      contraindications to the use of OAC. Only increasing age was significantly and
      independently associated with not being prescribed anticoagulants (p < 0.001). At
      the 4-year follow-up, OAC had been discontinued in 5.5% of patients because of
      major bleeding; three patients (4.1%) taking OAC had died as a result of major
      bleeding, and one other patient had discontinued treatment because of a major,
      non-lethal bleeding episode. CONCLUSION: Applying the NHG standard for
      appropriate prescription, and disregarding age as a risk factor or
      contraindication, in this population, 14 of 141 patients (9.9%) were
      inappropriately prescribed OAC, salicylates or no prophylaxis. Since only patient
      age was associated with not prescribing OAC in this study, higher age still seems
      to be considered the most important contraindication to anticoagulation therapy.
      Implementation of better models for stratifying bleeding risk in the frail
      elderly is needed. After 4 years, the cumulative rate of bleeding causing
      discontinuation of anticoagulation therapy in this usual-care study of frail
      older patients was not alarmingly higher than in other usual-care studies.

PMID- 20030432
TI  - Drug-induced, dementia-associated and non-dementia, non-drug delirium
      hospitalizations in the United States, 1998-2005: an analysis of the national
      inpatient sample.
AB  - BACKGROUND: The incidence and pattern of delirium recorded in a broad spectrum of
      American hospitalizations has not been well described. The National Inpatient
      Sample (NIS) of the Healthcare Cost and Utilization Project is an administrative
      database of hospitalizations in the US that affords an opportunity to examine for
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9) codes relating to delirium. OBJECTIVE: To examine the prevalence of
      delirium diagnoses and associated clinical factors, including adverse drug
      effects, in a broad spectrum of hospitalizations in the US. Delirium was grouped
      into three categories: drug-induced delirium, dementia-associated delirium, and
      non-dementia, non-drug (NDND). METHODS: Hospitalizations during the years 1998
      2005 in the NIS databases were examined. These databases represent samples of
      hospitalizations that allow for national prevalence estimates. ICD-9 codes for
      drug-induced, dementia-associated and NDND delirium were identified in the
      hospitalizations for each year. Delirium tremens was not considered in this
      classification, and paediatric and psychiatric admissions were excluded. Yearly
      prevalence for drug-induced, dementia-associated and NDND delirium were
      tabulated, and time trends were analysed with negative binomial regression. A
      hospitalization subset cohort with urinary tract/kidney infection, pneumonia,
      heart failure and lower extremity orthopaedic surgery diagnosis-related group
      categories was also analysed for clinical associations with the presence of the
      three categories of delirium using multinomial logistic regression. ICD-9 E codes
      (external causes of injury) constituting adverse drug effects were identified and
      considered as clinical predictors. RESULTS: Delirium was recorded in 1 269 185
      (0.54%) non-psychiatric adult hospitalizations during the study years. Whereas
      the overall prevalence of dementia-associated delirium and NDND delirium
      decreased over time, drug-induced delirium prevalence increased (p < 0.0001). As
      expected, the presence of dementia and adverse drug effects had the strongest
      associations with dementia-associated and drug-induced delirium, respectively, in
      the cohort hospitalizations. CONCLUSIONS: Drug-induced delirium and NDND delirium
      had the strongest associations with lower extremity orthopaedic surgery
      hospitalizations and urinary tract/kidney infection hospitalizations,
      respectively. Among the NDND co-morbid conditions, volume depletion and sodium
      imbalance had the strongest, albeit modest, associations with delirium. The
      association between decade of age and delirium was strongest for NDND delirium
      (adjusted odds ratio 1.53; 95% CI 1.52, 1.53), but age had significant
      associations with drug-induced and dementia-associated delirium as well. In the
      cohort, the most frequent adverse effects codes were for opioids and for
      benzodiazepines or other sedatives, which were noted in 21.3% and 15.2% of drug
      induced delirium hospitalizations, respectively. Drug-induced delirium is being
      increasingly identified in hospitalized patients. Administrative hospitalization
      databases constitute a resource to explore factors and trends associated with
      delirium. The findings suggest that interventions focusing on adverse drug
      effects have the greatest potential for preventing delirium.

PMID- 20030430
TI  - Anaesthesia for cataract surgery.
AB  - Cataract surgery is the most frequent surgical procedure requiring anaesthesia in
      developed countries. It is performed mainly in elderly patients, who present with
      many coexisting diseases that induce subsequent hazards from general anaesthesia.
      Cataract anaesthesia is performed following various techniques of regional
      anaesthesia, which are detailed in this review. Needle block carries a low but
      real risk of complications, mainly because of needle misplacement. Correct
      teaching and training are mandatory to prevent complications. The main patient
      risk factor for inadvertent globe perforation is the presence of a myopic
      staphyloma. Retrobulbar block has been progressively phased out and replaced by
      peribulbar block, sub-Tenon's block (STB) or topical anaesthesia (TA). The
      requirement for very deep block with total akinesia has greatly decreased with
      the use of phacoemulsification for cataract surgery, allowing for use of TA or
      low-volume STB. However, non-akinesia techniques may give rise to impaired
      surgical conditions, which have the potential to result in surgical
      complications. A surgical approach to accessing sub-Tenon's space avoids needle
      block, but does not totally prevent complications. When deep anaesthesia is
      required, low-volume STB, performed using either the needle technique or a
      surgical approach, appears to be the technique of choice in terms of efficacy.
      Increasing the anaesthetic volume provides reproducible akinesia. Various local
      anaesthetics may be used, depending on their availability and respective
      properties. The most useful adjuvant to local anaesthetic is hyaluronidase.

PMID- 20030433
TI  - Differential impact of NSAIDs on rate of adverse events that require
      hospitalization in high-risk and general veteran populations: a retrospective
      cohort study.
AB  - BACKGROUND: Many observational studies in the general population have
      demonstrated an increased risk of adverse events associated with NSAIDs,
      including gastrointestinal bleeds, congestive heart failure, acute renal failure,
      hypertension and acute myocardial infarction. Few studies, however, have explored
      outcomes in populations considered to be more vulnerable to their effects.
      OBJECTIVE: To determine the rate of adverse events requiring hospitalization that
      are associated with NSAIDs in two high-risk veteran populations and the general
      veteran population. METHODS: In this retrospective cohort study, we identified
      veterans being dispensed medicines for diabetes mellitus (diabetes cohort), those
      receiving renin-angiotensin system medicines and frusemide (furosemide)
      concurrently (ACE inhibitors/angiotensin II type 1 receptor antagonists
      [angiotensin receptor blockers; ARBs] and frusemide cohort), or at least one
      other medicine (general population/reference cohort). The primary endpoint was
      hospitalization with a primary diagnosis of congestive heart failure,
      gastrointestinal ulcer, acute renal failure, acute myocardial infarction or
      hypertension. Hospitalization rates during the period of non-exposure and the 30
      day period after a subject was first dispensed an NSAID were compared using
      Poisson regression. RESULTS: There was a significant increase in risk of all
      hospitalizations of interest in the exposed period compared with the unexposed
      period in the diabetes cohort (incidence rate ratio [IRR] 1.31; 95% CI 1.08,
      1.60), ACE inhibitor/ARB and frusemide cohort (IRR 1.34; 95% CI 1.13, 1.58) and
      reference cohort (IRR 1.47; 95% CI 1.30, 1.66). The incidence rates demonstrate
      that for every 10,000 veterans treated for 30 days with NSAIDs, there were 20
      extra hospitalizations in the diabetes population, 30 additional hospitalizations
      in the ACE inhibitor/ARB and frusemide cohort and 6 extra hospitalizations in the
      reference population compared with those not treated with NSAIDs. CONCLUSIONS:
      NSAID use is associated with an increased risk of hospitalization in all groups,
      with similar risk ratio estimates. However, the clinical implications were
      greater in the high-risk populations, in which more hospitalizations were
      observed. Consideration may need to be given to differential presentation of risk
      information to clinicians.

PMID- 20030434
TI  - Zonisamide in Parkinson's disease: profile report.

PMID- 20030435
TI  - Hylan G-F 20 single-injection formulation.
AB  - Hylan G-F 20, a cross-linked hyaluronic acid derivative, is an elastoviscous,
      high-molecular-weight (average 6000 kDa) fluid with rheological properties
      similar to those of knee synovial fluid of healthy young individuals. In a 26
      week, randomized, double-blind, multicentre study in patients with symptomatic
      primary osteoarthritis of the knee (n = 253), one intra-articular injection of
      hylan G-F 20 (single-injection formulation) into the target knee significantly
      relieved pain (as measured by the Western Ontario and McMaster Universities
      Osteoarthritis Index pain [WOMAC A] subscale), including pain while walking on a
      flat surface (as assessed by the WOMAC A1 subscore), compared with placebo.
      Observer-reported disease status and patient-reported health status were also
      significantly improved in hylan G-F 20-treated patients compared with placebo
      treated patients. A single intra-articular injection of hylan G-F 20 was
      generally well tolerated, with an adverse event profile similar to that of
      placebo. Repeat administration of hylan G-F 20 after 6 months had a similar
      tolerability profile to that of the initial injection. However, no patient who
      developed a target-knee adverse event after their first injection experienced
      such an event following their second injection.

PMID- 20030436
TI  - Subjective sleep quality alterations at high altitude.
AB  - OBJECTIVE: Sleep pattern at high altitude has been studied, mainly with the use
      of polysomnography. This study aimed to analyze subjective sleep quality at high
      altitude using the following standardized scales: the Pittsburgh Sleep Quality
      Index (PSQI) and the Athens Insomnia Scale (AIS-8). METHODS: Thirty-two members
      of 2 expeditions--28 males and 4 females (mean age 31 years)--participated in
      this study conducted in Nepal, Himalayas (Lobuche East, 6119 m above sea level
      [masl]), Kyrgyzstan, Pamirs (Lenin Peak, 7134 masl), and Poland (sea level). The
      scales were administered twice, at high altitude (mean altitude 4524 masl) and at
      sea level. RESULTS: Both measures showed a decrease in sleep quality at high
      altitude (statistical significance, P < .001). Sleep problems affected general
      sleep quality and sleep induction. Sleep disturbances due to awakenings during
      the night, temperature-related discomfort, and breathing difficulties were
      reported. High altitude had no statistically significant effect on sleep duration
      or daytime dysfunction as measured by PSQI. CONCLUSIONS: The overall results of
      PSQI and AIS-8 confirm the data based on the climbers' subjective accounts and
      polysomnographic results reported in previous studies. The introduction of
      standardized methods of subjective sleep quality assessment might resolve the
      problem of being able to perform precise evaluations and research in the field of
      sleep disturbances at high altitude.

PMID- 20030437
TI  - Determinants of summiting success and acute mountain sickness on Mt Kilimanjaro
      (5895 m).
AB  - OBJECTIVE: To determine the incidence of acute mountain sickness (AMS), the
      frequency of summiting success, and the factors that affect these in trekkers on
      Kilimanjaro, one of the world's most summitted high-altitude peaks. METHODS: The
      study group comprised 312 trekkers attempting Mt Kilimanjaro summit by the
      Marango Route. Trekkers ascended over 4 or 5 days along a fixed ascent profile,
      stopping at 3 huts on ascent (2700 m, 3700 m, and 4700 m) before attempting the
      summit. Researchers were stationed at each hut for 16 days. Each night we
      measured heart rate, respiratory rate, blood pressure, oxygen saturation, and
      Lake Louise Score. We recorded the highest altitude that trekkers reached on the
      mountain. RESULTS: Of 181 complete sets of data, 111 (61%) trekkers reached the
      summit, and 139 (77%) developed AMS. Physiological results were not related to
      summit success. The incidence of AMS and summiting success were similar in those
      on the 4- or 5-day route. Trekkers on the 5-day route who used acetazolamide were
      less likely to develop AMS and more likely to summit than were those not taking
      acetazolamide (P = <.05); this difference was not present with trekkers on the 4
      day route. CONCLUSIONS: The risk of developing AMS is high on Mt Kilimanjaro.
      Although taking an extra day to acclimatize with the use of acetazolamide did
      provide some protection against AMS, ideally trekkers need a more gradual route
      profile for climbing this mountain.

PMID- 20030438
TI  - Injury and illness encountered in Shenandoah National Park.
AB  - OBJECTIVE: There have been no studies to date exploring the nature of injuries
      and illness experienced by individuals in a National Park in the southeastern
      United States. The purpose of this study was to determine the incidence of such
      illnesses and injuries to visitors in Shenandoah National Park. METHODS: This
      study was a retrospective review of the case incident reports from Shenandoah
      National Park from 2003 to 2007. Data obtained included age, sex, time and date
      report was received, medical symptoms, trauma type, location of injury, mechanism
      of injury, level of care, time to patient, time to disposition, disposition type,
      location, and activity at time of event. RESULTS: There were 159 total cases,
      corresponding to a reported incident rate of 2.7 persons reported injured or ill
      per 100 000 visitors to Shenandoah National Park. A total of 23.3% of all
      reported injuries occurred in persons less than 18 years of age. The most common
      reported adult injury was soft tissue injury, with the most common anatomical
      location being the distal lower extremity. The most common activity in which
      adults were involved at the time of the injury was hiking. Of the pediatric
      trauma cases, the most common mechanism of injury was a fall. Of the adult
      medical illnesses, the most common complaint was chest pain. CONCLUSIONS: The
      pattern of adult and pediatric trauma is consistent among several geographically
      different National Parks in the United States and represents an injury pattern
      that all wilderness/outdoor care providers need to be competent to treat. Among
      adult visitors, the most common medical complaint was chest pain, a complaint
      more prevalent at Shenandoah National Park compared to other parks. Knowing that
      trauma injury patterns are relatively similar to those of other parks but that
      medical illness is more locale specific can help health care providers tailor
      their resource allotment and health management protocols.

PMID- 20030439
TI  - Injuries and medical conditions among kayakers paddling in the sea environment.
AB  - OBJECTIVE: Directly experienced health impacts and the perception of health
      impacts affecting the wider community kayaking in the sea environment were
      assessed. METHODS: Four hundred questionnaires were distributed at coastal launch
      sites in West Wales. One hundred and seventy-eight questionnaires were returned.
      RESULTS: The majority of respondents had not received injuries or developed
      medical conditions as a result of kayaking in the sea. Among those who had
      directly encountered health impacts, problems with joints, tendons, and muscles
      were the most frequently reported injury. When asked what were the most common
      health impacts in general among those who kayak in the sea, 'sprains and pulled
      muscles' and 'cuts and abrasions' were the most frequently cited factors. The
      rank order of the 'most common injury or medical condition' and the 'most
      commonly injured part of the body' varied according to type of boat used and
      activity undertaken. This variation was evident in relation to direct experience
      of health impacts and the perception of injuries and medical conditions affecting
      other kayakers. Most respondents regarded injuries and medical conditions as
      uncommon and not serious and reported positive health effects from kayaking.
      CONCLUSIONS: Health impacts encountered by those kayaking in the sea reflect many
      of those identified in literature focusing upon other aspects of kayaking.
      Responses to questions regarding the most common injury or medical condition and
      the most common injury site vary according to type of boat used and activity
      undertaken. It is concluded that while there may be common demands placed upon
      paddlers using a variety of boats and participating in differing activities, it
      cannot be assumed that they are a homogeneous group. This has implications for
      the development of incident prevention strategies.

PMID- 20030440
TI  - Recreational surfing injuries in Cornwall, United Kingdom.
AB  - OBJECTIVE: To analyze the nature of surfing injuries in Cornwall in order to
      identify trends and inform clinical management. METHODS: The details of patients
      presenting (with injuries sustained while surfboard/bodyboard riding) to the
      Emergency Department (ED) of the Royal Cornwall Hospital, Truro (UK), from
      September 2004 until August 2006 were recorded prospectively. The notes were then
      retrospectively reviewed by a senior ED physician. The records of each visit were
      scrutinized for date, age, sex, injury type, and injury severity and outcome; in
      addition, the patient's residential status (Cornish resident or visitor) was
      recorded. RESULTS: A total of 212 patient episodes were collected. Male patients
      represented 80% of injuries. The average age was 27 years (range, 11-66 years).
      Nonresident surfers represented 57% (121) of the patients, and 43% (91) of
      patients were local Cornwall residents. Of the total injuries, 90% (n = 190) were
      injuries that were minor/moderate (allowing for discharge after treatment).
      Lacerations accounted for 38% (n = 73) of injuries, and bruising and laceration
      to the head represented 37% (n = 71) of injuries in this group. Sprains to the
      neck and back represented 53% (21/40) of all sprains. Fractures of the facial
      bones represented 6 of the 8 fractures to the head region; the other 2 fractures
      involved teeth. Fractures to the upper and lower limbs were equally frequent (6
      cases of each). Anterior shoulder dislocations accounted for 10% (n = 19) of
      injuries not requiring hospital admission. Injuries requiring hospital admission
      represented 10% (n = 22). These injuries were a more disparate group, with
      fractures of the cervical spine and skull accounting for 32% (n = 7) and
      fractures of the lower limb 27% (n = 6) of the total. A total of 77% (n = 168) of
      all injuries presented in the summer months (April through September). The
      greatest number of presentations occurred in August, with 33% (n = 69) of the
      total surf-related injuries for the year. CONCLUSIONS: Surfing injuries were most
      common in young adult men. Most injuries presenting to the ED were minor/moderate
      injuries and did not require hospital admission. The overall pattern of injuries
      was similar to those found in studies from other countries where surfing is
      popular; however, there was a higher-than-expected incidence of shoulder
      dislocation. The trends identified in this study could be used to inform
      education focused on prevention of the most common injuries. Increased use of
      protective headwear should be considered.

PMID- 20030441
TI  - Latrodectism in New Caledonia: first report of presumed redback spider
      (Latrodectus hasselti) envenomation.
AB  - We describe a recent case of presumed redback spider (Latrodectus hasselti)
      envenomation observed near Noumea in New Caledonia. This is the first local
      reported case in this archipelago, where L. hasselti is currently considered a
      native species. We highlight the challenge of providing appropriate analgesia in
      this situation and believe that the use of specific redback spider antivenom
      should be considered in New Caledonia.

PMID- 20030442
TI  - Attack upon a bather by a swordfish: a case report.
AB  - We report a case of a bather injured by a swordfish in shallow water off the
      coast of southern Brazil. The victim suffered multiple injuries from the fish's
      bill, including a puncture wound of his left knee and the tip of the bill
      remaining as a foreign body. The victim made a full recovery after field
      management and conservative care. The potential factors leading to this most
      unusual attack are discussed.

PMID- 20030443
TI  - A long-duration (118-day) backpacking trip (2669 km) normalizes lipids without
      medication: a case study.
AB  - OBJECTIVE: To evaluate the effects of a long-distance backpacking trip on body
      composition, weight, blood lipids, and lipoproteins. METHODS: Single-subject
      (male, aged 49 years) study of an experienced backpacker who hiked 118 days on
      the Appalachian Trail. Outcome measures that were assessed pre-hike and post-hike
      included body fat (%) by hydrostatic weighing and skinfold assessment, height and
      weight, body mass index (BMI), circumference measurements (umbilicus, anterior
      suprailiac, maximum hip, greater trochanter, minimum waist, umbilicus/anterior
      suprailiac ratio), and blood pressure (systolic and diastolic at rest and peak).
      Dietary analyses (total kilocalories, protein, carbohydrate, fat, cholesterol,
      saturated fat, monounsaturated fat, polyunsaturated fat, dietary fiber) were
      conducted pre-hike, on days 54 through 56, and on days 98 through 100. Blood
      lipids and lipoproteins (triglycerides, high-density lipoprotein, low-density
      lipoprotein) were measured pre-hike, on day 89, and post-hike. RESULTS: Pre-post
      differences showed decreases in body weight, from 85.3 kg to 73.9 kg (-11.4 [
      13.4%]); percent body fat, hydrostatic weighing, from 25.18 to 14.31 (-10.87 [
      43.2%]); percent body fat, skinfolds (7-site), from 23.79 to 11.61 (12.18 [
      51.2%]); and BMI, from 29.37 to 25.46 (-3.91 [-13.3%]). Pre-post differences in
      blood lipid changes over the course of 118 days were as follows: triglycerides
      (mg x dL(-1)) fell from 319 to 79 (-240 [-75%]); total cholesterol (mg x dL(-1))
      fell from 276 to 196 (-80 [-29%]); high-density lipoprotein (HDL) (mg x dL(-1))
      rose from 46 to 63 (+17 [+37%]); low-density lipoprotein (LDL) (mg.dL(-1)) fell
      from 167 to 118 (-49 [-29%]); LDL/HDL ratio fell from 3.63 to 1.87 (-1.76 [
      48%]); and total cholesterol/HDL ratio fell from 6.00 to 3.11 (-2.89 [-48%]).
      CONCLUSION: The physical activity and diet associated with an extended
      backpacking adventure can considerably reduce and clinically normalize blood
      lipids and lipoproteins without medication and can very positively affect body
      composition and weight.

PMID- 20030444
TI  - Changes in plasma bradykinin concentration and citric acid cough threshold at
      high altitude.
AB  - OBJECTIVE: Altitude-related cough is a troublesome condition of unknown etiology.
      Inhaled tussive agents are used to quantify cough, and the citric acid cough
      threshold has been shown to fall on ascent to altitude. Cough can occur in
      patients taking angiotensin-converting enzyme inhibitors due to stimulation of
      airway sensory receptors by increased levels of bradykinin. We hypothesized that
      increased levels of bradykinin could be responsible for the decrease in citric
      acid cough threshold on exposure to altitude and a possible etiologic factor in
      altitude-related cough. METHODS: Twenty healthy volunteers underwent baseline
      tests at 700 m before a 2-week stay at 3800 m. Angiotensin-converting enzyme
      activity and plasma bradykinin were measured at baseline and altitude. Citric
      acid cough threshold and nocturnal cough frequency were measured at baseline and
      throughout the 2 weeks at altitude. RESULTS: Citric acid cough threshold fell
      from 3.7 g/dL at baseline to 2.1 g/dL on the second day at 3800 m (geometric mean
      difference 1.8, 95% CIs 1.0-5.0, P = .025) and remained reduced throughout the
      stay at altitude. Nocturnal cough frequency was unchanged compared to baseline.
      Plasma bradykinin fell from 0.43 ng/mL at baseline to 0.08 ng/mL at altitude
      (geometric mean difference 5.7, 95% CIs 2.1-15.5, P = .002), but angiotensin
      converting enzyme activity was unchanged (mean difference 0.06, 95% CIs -2.7-2.8,
      P = .97). There was no correlation between plasma bradykinin and citric acid
      cough threshold. CONCLUSIONS: Increased levels of bradykinin are unlikely to be a
      significant factor in the increased sensitivity to citric acid seen in hypobaric
      hypoxia. Further studies are required to elucidate the etiology of altitude
      related cough.

PMID- 20030445
TI  - Acute mountain sickness in children at 4380 meters in the Himalayas.
AB  - OBJECTIVE: To determine the incidence of and risk factors for acute mountain
      sickness (AMS) in native Nepalese children during a pilgrimage trip to Gosaikunda
      Lake in the Langtang National Park Region of Nepal (elevation 4380 m). METHODS: A
      descriptive, noninterventional, cross-sectional study was completed on a group of
      children during the pilgrimage to Gosaikunda. Participants were interviewed about
      the symptoms of AMS using the Lake Louise Scoring System. RESULTS: Thirty-six
      children between 3 and 15 years of age were interviewed after a rapid ascent
      (over 1 to 3 days) from 1950 m to 4380 m. Acute mountain sickness was diagnosed
      in 17 of 36 (47.2%) children. The sickness was seen in only 5 of 20 (25%)
      children who took 2 or more days to ascend, compared with 12 of 16 (75%) children
      who spent only 1 night (reaching the study site at Gosaikunda on the second day)
      to complete the same ascent (P < or = .01, odds ratio [OR] = 9.0, 1.61 < OR <
      57.36). No significant correlation was found between the incidence of AMS and
      gender, previous exposure to high altitude, or concurrent illness. CONCLUSIONS:
      Our results indicate that the incidence of AMS in this group of Nepalese children
      was high and associated with rapidity of ascent. Rapid ascent to high sleeping
      altitude and increased physical activity were observed as possible risk factors.
      We suggest organizing educational programs to make children and their parents
      aware of altitude-related problems and advise gradual ascent to such high
      altitude pilgrimage sites.

PMID- 20030446
TI  - A survey of snakebite management knowledge amongst select physicians in Hong Kong
      and the implications for snakebite training.
AB  - OBJECTIVE: The objective of the study was to assess the level of knowledge
      regarding snakebite management in doctors likely to treat such bites in the
      Special Administrative Region of Hong Kong in the People's Republic of China. Key
      concerns were doctor confidence, consistency of approach, use of anti-snake venom
      (ASV), and ancillary treatments. Hong Kong hospitals are equipped according to
      developed country standards, and knowledge therefore becomes the key factor in
      successful management. METHODS: A predesigned questionnaire consisting of 29
      multiple-choice questions was submitted to physicians likely to treat snakebite
      victims at all Hong Kong hospitals receiving such patients. RESULTS: The key
      finding identified that only 29% of responding doctors were confident about
      treating snakebites. In the case of ASV selection between the 2 products
      available that deal with different species, 66% of doctors either were unsure of
      which to use or believed the 2 ASVs to be the same. The use of inappropriate
      clinical endpoints for ASV therapy suggests it is being used unnecessarily.
      CONCLUSIONS: There is clear room for improvement in the knowledge base and
      confidence level of physicians treating snakebites in Hong Kong. Key components
      of management, such as ASV choice, indications, dosing, and clinical endpoints
      for administration, were sources of confusion to the participants in this study.
      The results demonstrate the need for a locally developed and widely distributed
      snakebite management protocol.

PMID- 20030447
TI  - A comparison of bacterial colony-forming units in water bottles and hydration
      bags among outdoor enthusiasts.
AB  - OBJECTIVE: Transporting clean drinking water in an easily accessible container is
      a priority for many outdoor enthusiasts. Two basic hydration systems are commonly
      used to provide water: the water bottle and the hydration bladder. The authors
      tested the hypothesis that there were different levels of microbiologic
      contamination between these 2 systems. METHODS: Sixty-seven water samples were
      collected using sterile techniques from outdoor enthusiasts at several outdoor
      recreational locations. These users were then asked to complete a brief survey
      that reported demographic information and details of water container use. Water
      samples were then plated on sheep blood agar, and the colony-forming units were
      counted after 24 hours of growth. The 2 groups were compared using Student's t
      test. RESULTS: The 2 groups using water bottles or hydration bladders did not
      show significant differences in container age, duration of outdoor activity, or
      duration since last cleaning. The groups differed slightly in their composition
      of hikers/walkers/runners vs cyclists. The water bottle group had a mean colony
      forming unit count per 100 mL of 37 (95% CI 26-48), and the hydration bladder had
      a mean of 27 (95% CI 17-35). CONCLUSIONS: There was no statistically significant
      difference between hydration bladders and water bottles in microbial
      contamination or colonization. Judging from the available data, outdoor
      enthusiasts should select their water container based on criteria other than the
      relative exposure to microbes. Additional study is required to replicate this
      finding in other locations and with improved sample methodology.

PMID- 20030448
TI  - The most dangerous catch: fisherman caught by halibut hook.

PMID- 20030449
TI  - Love and fear of heights: the pathophysiology and psychology of height imbalance.
AB  - Individual psychological responses to heights vary on a continuum from acrophobia
      to height intolerance, height tolerance, and height enjoyment. This paper reviews
      the English literature and summarizes the physiologic and psychological factors
      that generate different responses to heights while standing still in a static or
      motionless environment. Perceptual cues to height arise from vision. Normal
      postural sway of 2 cm for peripheral objects within 3 m increases as eye-object
      distance increases. Postural sway >10 cm can result in a fall. A minimum of 20
      minutes of peripheral retinal arc is required to detect motion. Trigonometry
      dictates that a 20-minute peripheral retinal arch can no longer be achieved in a
      standing position at an eye-object distance of >20 m. At this distance, visual
      cues conflict with somatosensory and vestibular inputs, resulting in variable
      degrees of imbalance. Co-occurring deficits in the visual, vestibular, and
      somatosensory systems can significantly increase height imbalance. An
      individual's psychological makeup, influenced by learned and genetic factors, can
      influence reactions to height imbalance. Enhancing peripheral vision and
      vestibular, proprioceptive, and haptic functions may improve height imbalance.
      Psychotherapy may improve the troubling subjective sensations to heights.

PMID- 20030450
TI  - Antarctic medicine--the challenges of being a doctor in an isolated and confined
      environment.

PMID- 20030452
TI  - An interesting cause of trauma: a ship's signal flare.

PMID- 20030453
TI  - Injury caused by the redtail botia, Botia modesta (Bleeker, 1865).

PMID- 20030454
TI  - In response to "Health screening on Aconcagua".

PMID- 20030455
TI  - Hypothermia in open-water swimming events: a medical risk that deserves more
      attention.

PMID- 20030457
TI  - In response to "Ankle-brachial index on Kilimanjaro: lessons from high altitude".

PMID- 20030459
TI  - Liver damage from chronic acetaminophen dosing is dangerous, but not the only
      risk.

PMID- 20030460
TI  - Thyroid disruption: mechanism and clinical implications in human health.
AB  - Exposure to specific environmental toxins, including polychlorinated biphenyls,
      dioxins, phthalates, polybrominated diphenyl ethers (PBDEs), and other
      halogenated organochlorines, has been shown to interfere with the production,
      transportation, and metabolism of thyroid hormones by a variety of mechanisms. A
      broad range of chemicals, with structural similarity to thyroid hormone, have
      been shown to bind to thyroid receptors with both agonist and antagonist effects
      on thyroid hormone signaling. The incidence of thyroid disease in the United
      States, particularly for thyroid cancer and thyroid autoimmune disease, is
      increasing substantially. The evidence for the significant effects of background
      levels of thyroid-disrupting chemicals, the known pathways for thyroid
      disruptors, and the evidence and implications for neurodevelopmental damage due
      to thyroid-disrupting chemicals is reviewed.

PMID- 20030461
TI  - Chlorinated pesticides: threats to health and importance of detection.
AB  - Although chlorinated pesticides have been mostly banned from use in the United
      States, their persistent presence in the environment poses an ongoing threat to
      health. Because of the lipophilic nature of chlorinated pesticides, they are
      bioaccumulative and difficult to excrete from the body. A select group of these
      xenobiotics is also associated with a wide range of health problems,
      identification of which would aid in disease prevention and reversal. Ongoing
      research by the Centers for Disease Control and Prevention now provides national
      standards for some of these compounds, allowing the clinician to evaluate levels
      in a patient. Serum samples are easily obtained and can reveal the presence of
      these xenobiotics. Eight of the most commonly found and harmful chlorinated
      pesticides are reviewed in this article, along with the most common sources of
      exposure and possible action steps.

PMID- 20030462
TI  - Did acetaminophen provoke the autism epidemic?
AB  - Schultz et al (2008) raised the question whether regression into autism is
      triggered, not by the measles-mumps-rubella (MMR) vaccine, but by acetaminophen
      (Tylenol) given for its fever and pain. Considerable evidence supports this
      contention, most notably the exponential rise in the incidence of autism since
      1980, when acetaminophen began to replace aspirin for infants and young children.
      The impetus for this shift - a Centers for Disease Control and Prevention warning
      that aspirin was associated with Reye's syndrome - has since been compellingly
      debunked. If aspirin is not to be feared as a cause of Reyes syndrome, and
      acetaminophen is to be feared as a cause of autism, can the autism epidemic be
      reversed by replacing acetaminophen with aspirin or other remedies?

PMID- 20030463
TI  - The relationship between Alzheimer's disease and diabetes: Type 3 diabetes?
AB  - In recent years, Alzheimer's disease (AD) has been considered to be, in part, a
      neuroendocrine disorder, even referred to by some as type 3 diabetes. Insulin
      functions by controlling neurotransmitter release processes at the synapses and
      activating signaling pathways associated with learning and long-term memory.
      Novel research demonstrates that impaired insulin signaling may be implicated in
      AD. Post-mortem brain studies show that insulin expression is inversely
      proportional to the Braak stage of AD progression. It was also demonstrated that
      neurotoxins, coined amyloid beta-derived diffusible ligands (ADDLs), disrupt
      signal transduction at synapses, making the cell insulin resistant. ADDLs reduce
      plasticity of the synapse, potentiate synapse loss, contribute to oxidative
      damage, and cause AD-type tau hyperphosphorylation. Diabetes and AD have signs of
      increased oxidative stress in common, including advanced glycation end products
      (AGEs), when compared to normal subjects. Diabetic patients appear to have an
      increased risk for AD because AGEs accumulate in neurofibrillary tangles and
      amyloid plaques in AD brains. This research should encourage a more proactive
      approach to early diagnosis of diabetes and nutritional counseling for AD
      patients.

PMID- 20030464
TI  - Essential oils in the treatment of intestinal dysbiosis: A preliminary in vitro
      study.
AB  - INTRODUCTION: Dysbiosis is associated with a number of gastrointestinal and
      systemic disorders. There is a need for selectively acting antimicrobial agents
      capable of inhibiting the growth of potentially pathogenic microorganisms, or
      those found to be out of balance, while not negatively impacting the bulk
      gastrointestinal tract microflora. OBJECTIVE: The purpose of this in vitro study
      is to examine the potential of a selection of essential oils as agents to treat
      dysbiosis. MATERIALS AND METHODS: Eight essential oils were examined using the
      agar dilution method, including Carum carvi, Citrus aurantium var. amara,
      Foeniculum vulgare dulce, Illicium verum, Lavandula angustifolia, Mentha
      arvensis, Mentha x piperita, and Trachyspermum copticum. Doubling dilutions of
      the essential oils were tested against 12 species of intestinal bacteria, which
      represent the major genera found in the human gastrointestinal tract (GIT).
      RESULTS: Carum carvi, Lavandula angustifolia, Trachyspermum copticum, and Citrus
      aurantium var. amara essential oils displayed the greatest degree of selectivity,
      inhibiting the growth of potential pathogens at concentrations that had no effect
      on the beneficial bacteria examined. CONCLUSION: The most promising essential
      oils for the treatment of intestinal dysbiosis are Carum carvi, Lavandula
      angustifolia, Trachyspermum copticum, and Citrus aurantium var. amara. The herbs
      from which these oils are derived have long been used in the treatment of
      gastrointestinal symptoms and the in vitro results of this study suggest that
      their ingestion will have little detrimental impact on beneficial members of the
      GIT microflora. More research is needed, however, to investigate tolerability and
      safety concerns, and verify the selective action of these agents.

PMID- 20030465
TI  - Silybin-phosphatidylcholine complex. Monograph.

PMID- 20030466
TI  - Docosahexaenoic acid (DHA). Monograph.

PMID- 20030467
TI  - Association of aldosterone concentration and mineralocorticoid receptor genotype
      with potassium response to spironolactone in patients with heart failure.
AB  - STUDY OBJECTIVE: To identify patient-specific factors associated with
      spironolactone-induced potassium level elevation in patients with heart failure.
      DESIGN: Prospective cohort study. SETTING: Two adult heart failure clinics.
      PATIENTS: Sixty-two adult (mean +/- SD age 54 +/- 16 yrs) aldosterone antagonist
      naive patients with heart failure. INTERVENTION: Patients received spironolactone
      12.5 mg/day, titrated to 25 mg/day if tolerated. MEASUREMENTS AND MAIN RESULTS:
      Blood samples were obtained at baseline, 1 week after spironolactone initiation,
      and 1 week after spironolactone dose titration for assessment of baseline
      aldosterone level, serum chemistry, and angiotensinogen (AGT) c.-6G>A and p.M268T
      and mineralocorticoid receptor (NR3C2) c.215C>G and p.I180V genotypes. Patient
      characteristics, laboratory values, and genotypes were compared between those
      whose potassium levels increased by more than 0.5 mEq/L (15 patients) and those
      with lower potassium level elevations (47 patients) after spironolactone
      initiation and dose titration. Patients with a greater potassium level elevation
      had a higher mean +/- SD aldosterone concentration (178 +/- 92 vs 102 +/- 57
      pg/ml, p=0.007) and NR3C2 215G allele frequency (50% vs 22%, p<0.01). Aldosterone
      concentrations positively correlated with diuretic dose (r=0.313, p=0.014) and
      negatively correlated with serum potassium level (r= -0.319, p=0.012). On
      regression analysis, factors predictive of potassium level increases greater than
      0.5 mEq/L with spironolactone were aldosterone level greater than 150 pg/ml (odds
      ratio [OR] 30, 95% confidence interval [CI] 3.2-287] and NR3C2 215G carrier
      status (OR 17, 95% CI 1.6-167). CONCLUSION: Our data suggest that potassium
      should be monitored with particular caution when spironolactone is started in
      patients with heart failure who have evidence of elevated aldosterone levels,
      such as high diuretic requirements, or the NR3C2 215G allele.

PMID- 20030468
TI  - Decreased T-cell responses to influenza vaccination in patients with heart
      failure.
AB  - STUDY OBJECTIVE: To determine whether T-cell immune responses to influenza
      vaccination in patients with chronic heart failure (CHF) are less vigorous than
      the responses of healthy control subjects. DESIGN: Prospective, single-center
      study. SETTING: University hospital and research laboratory. PARTICIPANTS:
      Eighteen adults with stable CHF receiving optimal treatment and 16 healthy
      control subjects. INTERVENTION: Participants were immunized with the 2006-2007
      trivalent inactivated (killed) influenza vaccine during October-December of 2006.
      MEASUREMENTS AND MAIN RESULTS: Blood samples were taken from the participants
      before and 2-4 weeks after vaccination to measure antibody titers, which were
      measured with a hemagglutination inhibition assay, then 3-4 months after
      vaccination to assess T-cell responses, measured by using the trans vivo delayed
      type hypersensitivity method. As part of this method, which mimics physiologic
      conditions, peripheral blood mononuclear cells were isolated from the blood
      samples. The cells were mixed with influenza vaccine antigens A/H1N1, A/H3N2, and
      B type and injected into the footpads of SCID mice (mice with severe combined
      immunodeficiency), as their resulting swelling is an index of human T-cell
      sensitization. Median T-cell-mediated immune responses to A/H3N2 were less
      vigorous in patients with CHF than in control subjects (62.5 vs 87.5 microm,
      unadjusted p=0.031, age-adjusted p=0.006). Median responses to A/H1N1 were not
      significantly different between the groups (56.3 vs 75 microm, p=0.11). Median
      responses to B type were also similar between the groups (62.5 vs 75 microm,
      p=0.47). All participants mounted an antibody response to the influenza vaccine.
      CONCLUSION: Patients with CHF had reduced T-cell responses to the influenza
      vaccine compared with healthy control subjects, as demonstrated by a lower
      response to A/H3N2, the newest antigen in the 2006-2007 vaccine. However,
      differences in T-cell immune responses to the A/H1N1 and B type strains were not
      found to be significant between the two groups, which suggests that patients with
      CHF can mount an appropriate response to vaccine antigens to which they have been
      previously exposed, but less so to new antigens. These findings suggest that
      patients with CHF may be at increased risk for influenza infection, and
      clinicians may want to investigate other or additional strategies for influenza
      vaccination.

PMID- 20030469
TI  - Plasma bile acid concentrations in patients with human immunodeficiency virus
      infection receiving protease inhibitor therapy: possible implications for
      hepatotoxicity.
AB  - STUDY OBJECTIVES: To evaluate whether patients with human immunodeficiency virus
      (HIV) infection who were receiving protease inhibitor therapy had altered bile
      acid concentrations compared with noninfected control subjects, and whether bile
      acid concentrations could predict the onset of hepatotoxicity caused by protease
      inhibitors. DESIGN: Retrospective sample analysis from a prospectively conducted
      clinical trial. SETTING: Academic research center. PATIENTS: Eleven adults with
      advanced HIV disease who were taking protease inhibitor-based antiretroviral
      therapy, one of whom had developed protease inhibitor-induced hepatotoxicity.
      MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cholic acid (CA),
      chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA),
      ursodeoxycholic acid (UDCA), and taurocholic acid (TC) were analyzed by using a
      novel high-performance liquid chromatography with tandem mass spectrometry
      detection method. Comparisons of the relative contribution of each bile acid to
      the total bile acid pool were made with previously published values and with bile
      acid concentrations contained in two pooled plasma samples from healthy, non-HIV
      infected volunteers analyzed in our laboratory. Each pooled plasma sample used
      for this analysis contained contributions from three non-HIV-infected volunteers.
      The LCA and TC concentrations in HIV-infected patients were 3-4-fold higher than
      those previously reported for non-HIV-infected subjects; concentrations of other
      bile acids were similar to those of previous reports. The relative contribution
      of CDCA to the total bile acid pool was 9% in HIV-infected patients compared with
      30-50% in noninfected subjects. Total and individual bile acid concentrations in
      the HIV-infected patient who developed hepatotoxicity were similar to the bile
      acid concentrations from the other study patients who did not develop
      hepatotoxicity. CONCLUSION: These data suggest that bile acid concentrations may
      be altered by HIV infection and/or protease inhibitor therapy. However, further
      investigations should be performed to assess whether antiretroviral-associated
      hepatotoxicity can be predicted by alterations in individual bile acid
      concentrations.

PMID- 20030470
TI  - Effects of acetaminophen, naproxen, and acetylsalicylic acid on tapentadol
      pharmacokinetics: results of two randomized, open-label, crossover, drug-drug
      interaction studies.
AB  - STUDY OBJECTIVE: To evaluate the effects of acetaminophen, naproxen, and
      acetylsalicylic acid on the pharmacokinetics of the centrally acting analgesic
      tapentadol in healthy subjects. DESIGN: Two randomized, open-label, crossover,
      drug-drug interaction studies. SETTING: Clinical research facilities in the
      United States and Belgium. PARTICIPANTS: Twenty-four healthy adults (2-way
      crossover study) and 38 healthy adults (3-way crossover study). INTERVENTIONS: In
      both studies, tapentadol immediate release (IR) 80 mg was administered as a
      single oral dose alone. In the 2-way crossover study, tapentadol IR was also
      given with the fifth of seven doses of acetaminophen 1000 mg; in the 3-way
      crossover study, tapentadol IR was also given with the third of four doses of
      naproxen 500 mg and the second of two doses of acetylsalicylic acid 325 mg. All
      treatments were separated by a washout period of 7-14 days. MEASUREMENTS AND MAIN
      RESULTS: Overall, mean serum concentrations were similar after administration of
      tapentadol IR alone and after coadministration with acetaminophen or
      acetylsalicylic acid, and the 90% confidence intervals (CIs) for the ratios of
      the mean area under the serum concentration-time curve (AUC) from time zero to
      time of the last measurable concentration (AUC(0-t)) and from time zero
      extrapolated to infinity (AUC(0-infinity)) and the maximum serum concentration
      (C(max)) of the combined treatments to those parameters of tapentadol alone were
      well within 80-125%, representing the accepted range for bioequivalence.
      Coadministration of naproxen did not significantly alter the C(max) of
      tapentadol, although a slightly higher serum tapentadol exposure relative to
      tapentadol alone was observed. Coadministration of naproxen resulted in a mean
      increase of 17% in AUCs, and the upper limits of the 90% CIs for the ratios of
      the mean AUC(0-t) and AUC(0-infinity) were slightly outside the upper limit of
      bioequivalence range of 80-125%(126.47%AUC(0-t) and 126.14%AUC(0-infinity)).
      CONCLUSION: No clinically relevant changes were noted in the serum concentrations
      of tapentadol, and accordingly, no dosage adjustments with respect to the
      investigated pharmacokinetic mechanism of interaction are warranted for the
      administration of tapentadol given concomitantly with acetaminophen, naproxen, or
      acetylsalicylic acid.

PMID- 20030471
TI  - Lack of effect of moderate hepatic impairment on the pharmacokinetics of
      telavancin.
AB  - STUDY OBJECTIVE: To evaluate the pharmacokinetics of the lipoglycopeptide
      antibiotic, telavancin, in patients with moderate hepatic impairment compared
      with healthy controls. DESIGN: Phase I, open-label, single-dose, matched-control,
      pilot study. SETTING: Clinical research unit. PARTICIPANTS: Eight adults with
      moderate hepatic impairment (Child-Pugh class B) and eight age-, sex-, and weight
      matched healthy control subjects. INTERVENTION: All participants received a
      single 1-hour intravenous infusion of telavancin 10 mg/kg. MEASUREMENTS AND MAIN
      RESULTS: Plasma samples were collected for pharmacokinetic analysis before the
      infusion and 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours after the start of the
      infusion. Concentrations of telavancin and the most prevalent of several minor
      hydroxylated metabolites, THRX-651540, were assayed with a validated liquid
      chromatography-tandem mass spectrometry technique. Telavancin binding to plasma
      proteins was determined in a preinfusion sample by using equilibrium dialysis.
      Pharmacokinetic parameters for telavancin and THRX-651540 were generally similar
      between the hepatic impairment and control groups. The mean maximum plasma
      concentration was 21% lower in patients with hepatic impairment than in controls,
      which was a statistically (analysis of variance, p<0.05), but not clinically,
      significant difference. There were no other statistically significant between
      group differences. Adverse events were few and mild. CONCLUSION: No apparent
      differences were observed in the pharmacokinetic disposition of telavancin in
      patients with hepatic impairment compared with healthy controls in this pilot
      study. Thus, adjustment of the standard telavancin dosage regimen does not appear
      to be required in patients with mild-to-moderate hepatic impairment.

PMID- 20030472
TI  - Once-daily gentamicin dosing in children with febrile neutropenia resulting from
      antineoplastic therapy.
AB  - STUDY OBJECTIVES: To evaluate an existing once-daily gentamicin dosing guideline
      in children with febrile neutropenia resulting from antineoplastic therapy and,
      if necessary, to develop a new simulated dosing guideline that would achieve
      pharmacokinetic targets more reliably after the first dose. DESIGN:
      Pharmacokinetic analysis of data from a retrospective medical record review.
      SETTING: Hematology-oncology unit of a university-affiliated pediatric hospital
      in Canada. PATIENTS: One hundred eleven patients aged 1-18 years who received
      once-daily gentamicin between April 2006 and January 2008 for the treatment of
      febrile neutropenia resulting from antineoplastic therapy, and who had plasma
      gentamicin concentrations determined after their first dose. MEASUREMENTS AND
      MAIN RESULTS: Demographic data, gentamicin dosing information, blood sampling
      times, and plasma gentamicin concentrations were noted. Plasma gentamicin
      concentrations were determined at approximately 3 and 6 hours after the start of
      the 30-minute infusion of the first dose. Pharmacokinetic parameters were
      calculated according to standard first-order, one-compartment equations. The
      proportion of children who achieved pharmacokinetic targets after the first
      gentamicin dose was used as a measure of dosing guideline performance; the
      guideline achieved maximum concentration (C(max)) values below the target range
      (20-25mg/L) in 51% of patients. Ideal dosing guidelines were then developed using
      the mean dose required to achieved a C(max) of 23 mg/L for each patient.
      Univariate analysis or the Student t test was used to determine the existence of
      significant relationships between pharmacokinetic parameters and patient age and
      sex. The recursive binary partitioning method was used to determine critical
      values of age for dosage guideline development; analysis of variance was then
      used to compare the different levels obtained after use of this technique.
      Simulated administration of once-daily gentamicin in the following doses achieved
      a C(max) within or above target in 73% of patients: 1 year to < 6 years,
      10.5mg/kg/dose; girls > or = 6 years, 9.5mg/kg/dose; and boys > or = 6 years,
      7.5mg/kg/dose. Doses were based on actual body weight for children who weighed
      less than 125% of ideal body weight or based on effective body weight for
      children 125% or more of ideal body weight. CONCLUSION: The initial gentamicin
      dosing guidelines were not effective in achieving C(max). The new proposed dosing
      guidelines are predicted to achieve a C(max) within or above the target range in
      almost three quarters of patients. Subsequent dosing should be tailored according
      to plasma gentamicin concentrations.

PMID- 20030473
TI  - Lack of association between excretion of sorafenib in sweat and hand-foot skin
      reaction.
AB  - STUDY OBJECTIVE: To determine if excretion of sorafenib in sweat is associated
      with hand-foot skin reaction in patients receiving sorafenib. DESIGN: Prospective
      pilot study. SETTING: Outpatient clinic of a cancer research institution.
      PATIENTS: Two patients who were receiving sorafenib and developed a hand-foot
      skin reaction of at least grade 1 and two healthy subjects (controls).
      INTERVENTION: Sweat production was stimulated in both the patients with hand-foot
      skin reaction and the healthy subjects by means of pilocarpine iontophoresis.
      MEASUREMENTS AND MAIN RESULTS: Sweat samples were collected from the patients
      with hand-foot skin reaction and from the healthy subjects. Using liquid
      chromatography-tandem mass spectrometry, sorafenib concentrations were measured
      in the sweat samples. Sweat samples from the healthy subjects were spiked with
      known concentrations of sorafenib to determine the lower limit of quantification
      of the assay, which was determined to be 5 ng/ml. Sorafenib concentrations in the
      samples from the patients with hand-foot skin reaction were undetectable based on
      the assay's sensitivity. CONCLUSION: Our results suggest that hand-foot skin
      reaction in patients receiving sorafenib is not associated with excretion of
      sorafenib in sweat. Further studies are needed to understand the mechanism of
      hand-foot skin reaction, a treatment-limiting adverse effect of multikinase
      inhibitors.

PMID- 20030474
TI  - Drug fever.
AB  - Drug fever is a common condition that is frequently misdiagnosed. It is a febrile
      response that coincides temporally with the administration of a drug and
      disappears after discontinuation of the offending agent. Drug fever is usually
      suspected when no other cause for the fever can be elucidated, sometimes after
      antimicrobial therapy has already been started. In nonsensitized individuals
      receiving a drug for the first time, the onset of fever is highly variable and
      differs among drug classes, but most commonly appears after 7-10 days of drug
      administration and rapidly reverses after discontinuation of the drug. Early
      diagnosis may reduce inappropriate and potentially harmful and expensive
      diagnostic and therapeutic interventions. Rechallenge with the offending agent
      will usually cause recurrence of fever within a few hours, confirming the
      diagnosis. Rechallenge is controversial and should be performed with extreme
      caution, since there is a potential for a more severe drug reaction. We describe
      the mechanisms in the pathophysiology of drug fever and summarize the results of
      published case reports on the wide variety of agents that are implicated in
      causing drug fever. Special attention is paid to the role of antimicrobial agents
      in drug fever.

PMID- 20030475
TI  - Ferumoxytol: a new intravenous iron preparation for the treatment of iron
      deficiency anemia in patients with chronic kidney disease.
AB  - Ferumoxytol is an intravenous iron preparation for treatment of the anemia of
      chronic kidney disease (CKD). It is a carbohydrate-coated, superparamagnetic iron
      oxide nanoparticle. Because little free iron is present in the preparation, doses
      of 510 mg have been administered safely in as little as 17 seconds. Two
      prospective, randomized studies compared two doses of ferumoxytol 510 mg given in
      5 +/- 3 days with 3 weeks of oral iron 200 mg/day (as ferrous fumarate) in anemic
      patients with CKD. One study enrolled 304 patients with stages 1-5 CKD
      (predialysis), and the other study enrolled 230 patients with stage 5D CKD
      (undergoing hemodialysis). In both studies, a greater increase in hemoglobin
      level from baseline to end of study (day 35) was noted in patients who received
      ferumoxytol compared with those who received oral iron (mean +/- SD 0.82 +/- 1.24
      vs 0.16 +/- 1.02 g/dl in patients with stages 1-5 CKD and 1.02 +/- 1.13 vs 0.46
      +/- 1.06 g/dl in patients with stage 5D CKD, p<0.001). A greater proportion of
      both predialysis and hemodialysis patients who received ferumoxytol had
      hemoglobin level increases from baseline of 1 g/dl or more compared with those
      who received oral iron (p<0.001). In a prospective, double-blind, crossover study
      of more than 700 patients with CKD stages 1-5D that compared the safety of
      ferumoxytol with normal saline injection, the rates of treatment-related adverse
      events were 5.2% and 4.5%, respectively. Serious treatment-related adverse events
      were seen in one patient in each treatment group. The most common adverse events
      with ferumoxytol occurred at the injection site (bruising, pain, swelling,
      erythema). Dizziness, nausea, pruritus, headache, and fatigue occurred in less
      than 2% of patients receiving ferumoxytol, with a similar frequency noted after
      administration of normal saline. In short-term studies, intravenous ferumoxytol
      was safely and rapidly administered, and was more effective than oral iron
      therapy in increasing hemoglobin levels in anemic patients with CKD. Long-term
      clinical trials with clinical outcomes and studies comparing ferumoxytol with
      other parenteral iron agents will help define the role of ferumoxytol in treating
      the anemia of CKD.

PMID- 20030476
TI  - A comparative review of the lipoglycopeptides: oritavancin, dalbavancin, and
      telavancin.
AB  - Resistance to antibiotics among gram-positive bacteria, especially enterococci
      and staphylococci, has led to the need to develop new antibiotics. Vancomycin, a
      glycopeptide antibiotic, has been used for over 3 decades to treat serious
      methicillin-resistant Staphylococcus aureus infections. The increased frequency
      of multidrug-resistant bacteria, especially vancomycin-resistant strains, has
      focused interest on three new lipoglycopeptides for the treatment of infections
      caused by gram-positive bacteria: oritavancin, dalbavancin, and telavancin.
      Although oritavancin and dalbavancin are still in development, telavancin
      received approval from the United States Food and Drug Administration in
      September 2009 for treatment of complicated skin and skin structure infections.
      Structurally different from vancomycin and teicoplanin, all three
      lipoglycopeptides have greater potency and less potential for development of
      resistant organisms. Of particular importance is the activity of oritavancin,
      dalbavancin, and telavancin against vancomycin-resistant organisms. In addition,
      the pharmacokinetic properties of these new antimicrobials substantially differ
      from those of vancomycin. Both oritavancin and dalbavancin have long terminal
      half-lives, which may allow for infrequent dosing. In addition, oritavancin is
      primarily cleared through hepatic pathways, which makes it potentially useful in
      patients with renal compromise. In animal models, these new lipoglycopeptides
      were effective in treating serious gram-positive infections, including
      complicated skin and skin structure infections, endocarditis, bacteremia, and
      pneumonia; in clinical studies, however, efficacy was shown only in complicated
      skin and skin structure infections for all three agents. According to preliminary
      data, the adverse-effect profile of these lipoglycopeptides is generally similar
      to that of drugs currently used to treat severe gram-positive infections.
      However, further evaluation and monitoring is necessary as more patients are
      exposed to these agents. As antimicrobial resistance continues to increase
      worldwide, the lipoglycopeptides may provide clinicians with a useful
      antimicrobial in the continued fight against multidrug-resistant gram-positive
      bacteria.

PMID- 20030477
TI  - Extended-interval once-daily dosing of aminoglycosides in adult and pediatric
      patients with cystic fibrosis.
AB  - Extended-interval once-daily dosing with the aminoglycoside tobramycin has been
      proven to be equally efficacious as traditional thrice-daily dosing for treatment
      of the pulmonary exacerbations of cystic fibrosis in adults and children older
      than 5 years. The frequencies of acute ototoxicity and nephrotoxicity do not
      appear to be significantly different between patients treated with once- versus
      thrice-daily dosing, and the risk of acute nephrotoxicity may actually be lower
      in pediatric patients when once-daily dosing is used. Long-term studies are
      needed to fully assess the impact that cumulative treatments with once-daily
      dosing have on renal and auditory function. An increase in antimicrobial
      resistance has been suggested with once-daily dosing in the cystic fibrosis
      population. The extended-interval aminoglycoside dose should be determined based
      on previous therapeutic drug monitoring. If the patient is aminoglycoside
      (tobramycin) naive, a dose of 10 mg/kg once/day is suggested, with the dose
      adjusted by using therapeutic drug monitoring to individualize therapy.

PMID- 20030478
TI  - Key articles related to complementary and alternative medicine in cardiovascular
      disease: part 1.
AB  - Complementary and alternative medicine (CAM) therapy has gained popularity in
      America over the past several years, reflected in the increased utilization of
      these agents. Given the abundance of nontraditional products available to the
      public, clinicians should be made aware of the existing evidence relating to CAM
      therapy to better provide patient care in a meaningful manner. This bibliography
      article compiled key articles specific to CAM therapy and cardiovascular disease,
      which include primary literature, review articles, consensus statements, and
      abstracts of landmark studies. Based on the numerous published reports available
      on this topic, this bibliography, as part 1 of 2, focuses on the efficacy of CAM
      therapy in cardiovascular disease.

PMID- 20030479
TI  - Probable warfarin interaction with menthol cough drops.
AB  - Warfarin is a widely used and effective oral anticoagulant; however, the agent
      has an extensive drug and food interaction profile. We describe a 46-year-old
      African-American man who was receiving warfarin for a venous thromboembolism and
      experienced a decrease in his international normalized ratio (INR). No
      corresponding reduction had been made in his warfarin dosage, and no changes had
      been made in his concomitant drug therapy or diet. The patient's INR fell from a
      therapeutic value of 2.6 (target range 2-3) to 1.6 while receiving a weekly
      warfarin dose of 50 mg. His INR remained stable at 1.6 for 3 weeks despite
      incremental increases in his warfarin dose. The patient reported that he had been
      taking 8-10 menthol cough drops/day due to dry conditions at his workplace during
      the time period that the INR decreased. Five days after discontinuing the cough
      drops, his INR increased from 1.6 to 2.9. Over the subsequent 5 weeks, his INR
      was stabilized at a much lower weekly warfarin dose of 40 mg. Use of the Naranjo
      adverse drug reaction probability scale indicated that the decreased INR was
      probably related to the concomitant use of menthol cough drops during warfarin
      therapy. The mechanism for this interaction may be related to the potential for
      menthol to affect the cytochrome P450 system as an inducer and inhibitor of
      certain isoenzymes that would potentially interfere with the metabolism of
      warfarin. To our knowledge, this is the second case report of an interaction
      between warfarin and menthol. Patients receiving warfarin should be closely
      monitored, as they may choose to take over-the-counter products without
      considering the potential implications, and counseled about a possible
      interaction with menthol cough drops.

PMID- 20030480
TI  - Treatment of methotrexate intoxication with various modalities of continuous
      extracorporeal therapy and glucarpidase.
AB  - Methotrexate, administered for treatment of pediatric and adult malignancies, is
      a direct renal toxin, which can lead to renal dysfunction, decreased methotrexate
      clearance, elevated methotrexate concentrations, and systemic toxicity. Although
      plasma methotrexate concentrations have been shown to decline precipitously after
      a single dose of glucarpidase, this drug is investigational and available only
      through compassionate use. Therefore, alternative treatments for methotrexate
      removal may be required. We describe a 13-year-old girl (body surface area 1.2
      m(2)) with osteosarcoma who was treated with high-dose methotrexate 12 g/m(2)
      infused over 4 hours. Forty-eight hours after the infusion, her plasma
      methotrexate concentrations were elevated at 446 micromol/L. She exhibited severe
      signs of methotrexate toxicity, including encephalopathy, liver failure, and
      acute kidney injury, and could not tolerate conventional hemodialysis. Over the
      next 12 days, the patient was treated with continuous venovenous hemodialysis
      (CVVHD), single-pass albumin dialysis (SPAD), continuous venovenous
      hemodiafiltration (CVVHDF), and glucarpidase to enhance methotrexate elimination.
      Compared with standard CVVHD, SPAD did not significantly increase methotrexate
      removal as measured by elimination half-life and methotrexate saturation
      coefficient. The highest clearance rate among extracorporeal therapies was
      achieved by CVVHDF, with an effluent rate of 4950 ml/hour. The patient's clinical
      condition steadily improved, and all extracorporeal therapies were stopped 168
      hours after methotrexate administration. The patient was discharged home and
      continued with chemotherapy, including methotrexate, which was dosed based on
      iothalamate glomerular filtration rates on the day before infusion. Although
      extracorporeal treatments appeared to enhance methotrexate clearance, the
      administration of glucarpidase resulted in the most rapid percentage decline
      (86%) in methotrexate concentration. Until glucarpidase is readily available,
      intermittent hemodialysis should be used to enhance methotrexate clearance. If
      the patient is unable to tolerate hemodialysis, use of CVVHDF with maximum
      effluent rates will enhance methotrexate clearance.

PMID- 20030482
TI  - Mercaptopurine-induced fever: hypersensitivity reaction in a patient with acute
      lymphoblastic leukemia.
AB  - The antimetabolite mercaptopurine is commonly used as part of treatment regimens
      for acute lymphoblastic leukemia and as treatment for inflammatory bowel
      diseases. Adverse effects associated with mercaptopurine include
      myelosuppression, hepatotoxicity, and hyperpigmentation. We describe a 36-year
      old man with Philadelphia chromosome-negative pre-B-cell acute lymphoblastic
      leukemia who experienced a serious mercaptopurine-induced hypersensitivity
      reaction requiring prolonged hospitalization and extensive laboratory testing and
      imaging. He was treated with a multiagent chemotherapy regimen. Mercaptopurine 60
      mg/m(2)/day orally was started as part of his third course of chemotherapy. On
      day 9 of mercaptopurine therapy, the patient developed persistent fevers, skaking
      chills, and rigors that persisted in the absence of documented infection,
      consistent with drug fever. All symptoms and signs resolved after discontinuation
      of mercaptopurine. Use of the Naranjo adverse drug reaction probability scale
      indicated a probable relationship between the patient's development of fever and
      mercaptopurine therapy. Mercaptopurine-induced fever has been reported in
      patients with inflammatory bowel diseases, but this case report is the first, to
      our knowledge, in a patient with acute lymphoblastic leukemia. Health care
      professionals should be aware of the possible development of fever as a
      hypersensitivity reaction in patients with acute lymphoblastic leukemia treated
      with mercaptopurine.

PMID- 20030481
TI  - Sudden sensorineural hearing loss associated with vardenafil.
AB  - The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and
      tadalafil-are used primarily in erectile dysfunction, but sildenafil is also
      indicated for pulmonary hypertension. Common adverse effects of vardenafil
      include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently,
      PDE-5 inhibitors have been associated with adverse vision effects, and emerging
      evidence now indicates that they may also be responsible for hearing changes and
      hearing loss. We describe a patient who developed unilateral sudden sensorineural
      hearing loss possibly related to the use of vardenafil for erectile dysfunction.
      To our knowledge, only one other case of hearing loss related to this drug class
      has been published. Our patient was a 57-year-old man who came to the emergency
      department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz
      range, confirmed by audiogram, that occurred after ingestion of vardenafil. The
      patient was hospitalized 2 days later for administration of intravenous
      dexamethasone, followed by oral prednisone. He reported that his hearing had
      improved on the fourth hospital day and was discharged 3 days later, continuing
      to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days
      of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was
      within normal limits. Use of the Naranjo adverse drug reaction probability scale
      indicated a possible (score of 3) adverse reaction of sudden sensorineural
      hearing loss associated with vardenafil consumption. We also performed an
      analysis of hearing loss cases related to PDE-5 inhibitors in the United States
      Food and Drug Administration's Adverse Event Reporting System database to compare
      the characteristics of our patient with those of other reported adverse event
      cases. Based on the temporal relation of the sudden sensorineural hearing loss to
      this patient's drug consumption, we propose that the vardenafil is a likely cause
      of the hearing loss. This case provides further evidence that PDE-5 inhibitor
      consumption should be considered as a possible cause in patients presenting with
      sudden sensorineural hearing loss.

PMID- 20030483
TI  - Rewards and advancements for clinical pharmacists.
AB  - The American College of Clinical Pharmacy charged the Clinical Practice Affairs
      Committee to review and update the College's 1995 White Paper, "Rewards and
      Advancements for Clinical Pharmacy Practitioners." Because of the limited data on
      the present state of rewards and advancements for clinical pharmacists, an online
      survey of "front-line" clinical pharmacists and pharmacy managers was conducted
      (1126 total respondents, 14% response rate). The resulting White Paper discusses
      motivators and existing systems of rewards and advancements for clinical
      pharmacists, as well as perceived barriers to implementation of these systems.
      Clinical pharmacists reported work-life balance, a challenging position, and
      opportunities for professional advancement as the most important factors for
      career success. At the time of the survey, financial rewards appeared not to be a
      major motivator for clinical pharmacists. Managers underestimated the importance
      that clinical pharmacists place on work-life balance and favorable work
      schedules. Although almost two thirds of the clinical pharmacists surveyed had
      not developed a professional development plan, 84% indicated an interest in
      career planning. Both clinical pharmacists and managers rated the lack of a clear
      reward and advancement structure as the most important barrier to effective
      systems of rewards and advancements. Pharmacy managers and administrators are
      encouraged to develop effective systems of rewards and advancements for clinical
      pharmacists that positively impact patient care and the institution's mission;
      these systems will benefit the clinical pharmacist, the health care institution,
      and the patient.

PMID- 20030484
TI  - The projective identifications of everyday life.

PMID- 20030485
TI  - Whose hate is it? Encountering emotional turbulence in the crosscurrents of
      projective identification and countertransference experience.

PMID- 20030486
TI  - Falling into sexuality: sexual boundary violations in psychotherapy.

PMID- 20030487
TI  - Interpreting the sense of badness.

PMID- 20030488
TI  - The dramatic meaning of madness in psycho(analy)sis: the ear-rationality of
      treating illusion as reality.

PMID- 20030489
TI  - Do ask, do tell? Narcissistic need as a determinant of analyst self-disclosure.

PMID- 20030490
TI  - Precreative space.

PMID- 20030491
TI  - The extermination of extimacy: an internal view of a city hospital community.

PMID- 20030495
TI  - Increasing parent involvement in youth HIV prevention: a randomized Caribbean
      study.
AB  - This article presents preliminary findings of a randomized HIV prevention study
      in Trinidad and Tobago in the Caribbean. The study centers on a family HIV
      workshop aimed at strengthening parenting skills that are empirically linked to
      reducing adolescent HIV exposure and other sexual risks. These skills include
      parental monitoring; educating youth about HIV, sex, and other sexually
      transmitted infections (STI's); and discussing cultural and interpersonal
      pressures to have sex. Participants include 180 primary caregivers and their 12
      14-year-old adolescents randomized to either the Trinidad and Tobago family HIV
      Workshop (N = 92) or a general workshop (N = 88). Intervention and control group
      participants completed pretest and posttest measures on parenting and HIV risk
      outcomes. Compared to controls, intervention parents reported improvements in HIV
      knowledge (d = .79); attitudes toward AIDS (d = .42); general communication with
      adolescents (d = .94); conversations with adolescents about sex (d = .95);
      conversations about sexual risks and values (d = .43); monitoring of adolescents
      (d = .34); conflicts with adolescents (d = .30); and intensity of daily parenting
      hassles (d = .35). Intervention and control parents did not differ in behavioral
      control, use of positive parenting techniques, and expansion of support networks.
      Implications for addressing rising HIV risks among young people in Trinidad and
      Tobago and the Caribbean are discussed.

PMID- 20030496
TI  - Promoting continuous use as a strategy for achieving adherence in a trial of the
      diaphragm with candidate microbicide.
AB  - Women need more choices for protection from HIV and other sexually transmitted
      infections (STIs). We conducted a randomized 4-week study in Madagascar in
      preparation for a Phase III randomized controlled trial (RCT) of the diaphragm
      with a candidate microbicide for STI prevention. All participants completed
      quantitative surveys; half participated in a qualitative interview. We advised
      women to wear the diaphragm at all times except for daily cleaning (rather than
      inserting it before intercourse). The objective of this analysis was to determine
      whether women who followed this "continuous use" approach more often used the
      diaphragm for 100% of sex acts as compared with other women. If so, this would
      support advising continuous diaphragm use in the upcoming RCT. To meet our
      objective, we analyzed qualitative data thematically, developed a measure of
      continuous diaphragm use based on qualitative data, and used multiple regression
      to evaluate the measure's association with adherence to diaphragm use during 100%
      of sex acts. Women who wore the diaphragm continuously had 4 times higher odds of
      reporting diaphragm use during 100% of sex acts (OR: 4.6, 95% CI: 1.2, 24.0). If
      the diaphragm proves effective against STI, continuous use may help women achieve
      high levels of protection.

PMID- 20030497
TI  - Perceptions of vulnerability to HIV/AIDS: a comparison of two college cohorts,
      1990 and 2005.
AB  - Theories of preventive health behavior posit that perceived vulnerability to
      health threats motivates self-protective behavior. Fifteen years after an initial
      study of college students' perceptions of their vulnerability to HIV, a
      replication was conducted on the same campus in 2005. Comparisons between cohorts
      on vulnerability judgements were conducted to examine whether, and to what
      extent, student perceptions had changed across time. Respondents in the 1990
      study had judged themselves as less vulnerable to HIV/AIDS than others about whom
      they also made risk estimates; this pattern was replicated among 2005
      respondents, even though many in both cohorts were involved in objectively risky
      practices. Comparisons between the cohorts on risk behaviors revealed that fewer
      of the 2005 students reported being sexually active, and those who were active
      used condoms more frequently. However, 2005 respondents also reported more
      recreational drug use, and oral and anal sexual activity than the 1990 students.

PMID- 20030498
TI  - Acceptability and use of the female condom and diaphragm among sex workers in
      Dominican Republic: results from a prospective study.
AB  - To assess the acceptability and use of the female condom and diaphragm among
      female sex workers in the Dominican Republic, 243 participants were followed for
      5 months. Participants received female and male condoms and a diaphragm along
      with proper counseling at monthly visits. Seventy-six percent reported used of
      female condom at least once during the final month of the study, compared with
      50% that used the diaphragm with male condoms and 9% that used the diaphragm
      alone. The proportion of women reporting every sex act protected with some
      barrier method increased from 66% at first month to 77% at final month (p <
      0.05). Participants reported higher acceptability and use of the female condom
      than the diaphragm. The introduction of female-controlled barrier methods
      resulted in the use of a wide range of prevention methods and a significant
      reduction in unprotected sex.

PMID- 20030499
TI  - Pairing HIV-positive prisoners with volunteer life coaches to maintain health
      promoting behavior upon release: a mixed-methods needs analysis and pilot study.
AB  - Drawing on individuals who volunteer in US prisons to mentor HIV-infected inmates
      returning to the community may promote successful transitions. Evaluations
      published in the scientific literature of such community linkage programs are
      scant. Our quantitative and qualitative methods needs analysis and pilot study
      entailed interviewing convenience samples of 24 HIV-positive persons recently
      released from Georgia correctional facilities and 12 potential volunteer mentors.
      Both releasees and potential mentors were open to the establishment of a
      mentoring program. Releasees wanted nonjudgmental mentors. Releasees and
      volunteers had statistically significant differences in marital status,
      education, current employment, and possession of a driver's license but not in
      degree of religious involvement and attitudes toward condom use. A volunteer
      staffed program, perhaps more aptly named "life coaching" than mentoring, to help
      HIV-infected persons to transition from prison to the community may be feasible.
      Success will require adequately trained volunteers and a straightforward program.

PMID- 20030500
TI  - Knowledge, attitudes, and practices of voluntary HIV counseling and testing among
      rural migrants in Shanghai, China.
AB  - A study of knowledge, attitudes and practices (KAP) of voluntary HIV counseling
      and testing (VCT) among rural migrants was conducted in Shanghai, China. An
      anonymous questionnaire was administered face-to-face. Among 2,690 participants,
      78% reported having had lifetime sexual intercourse with 41.3% of singles
      reporting sexual intercourse, 9.2% having had multiple sex partners in the past
      year, only 19% of the participants always using condoms whereas 61.6% did not use
      in their sexual acts in the past month, 80% knew HIV infection was diagnosed
      through a blood test, 46.5% had heard of VCT ever before, but only 3.5% felt that
      they were likely to be HIV-infected now or in the future and only 62 (2.3%) had
      ever had HIV testing with 19 of them getting tested at a VCT site. Gender,
      working venue, multiple sex partnerships and knowledge of VCT were independently
      correlated with having had HIV testing. This study suggests that a much greater
      effort is needed to promote safer sex and to improve VCT knowledge and services
      among rural migrants particularly those who are engaging in risky behaviors.

PMID- 20030501
TI  - "It's better not to know": perceived barriers to HIV voluntary counseling and
      testing among sub-Saharan African migrants in Belgium.
AB  - This study explored perceptions, needs, and barriers of sub-Saharan African
      migrants in relation to HIV voluntary counseling and testing (VCT). Using an
      inductive qualitative methodological approach, data were obtained from focus
      group discussions. Results showed that participants were in principle in favor of
      VCT. However, they indicated that barriers outweighed advantages. Such barriers
      included fear of positive test results and its related personal and social
      consequences, lack of information, lack of preventive health behavior, denial of
      HIV risk, and missed opportunities. Limited financial resources were only a
      concern for some subgroups like young people, asylum seekers, and recent
      migrants. This study identified multiple and intertwined barriers to VCT from a
      community perspective. In order to promote VCT, interventions such as raising
      awareness through culturally sensitive education should be adopted at community
      level. At level of service provision, provider initiated HIV testing including
      target group tailored counseling should be promoted.

PMID- 20030503
TI  - Formulation of intranasal mucoadhesive temperature-mediated in situ gel
      containing ropinirole and evaluation of brain targeting efficiency in rats.
AB  - Mucoadhesive temperature-mediated in situ gel formulations using chitosan and
      hydroxyl propyl methyl cellulose were used to enhance intranasal (i.n.) delivery
      of the dopamine D2 agonist ropinirole to the brain. Formulations were tested for
      gelation time, thermosensitivity, mucoadhesion, in vitro release and permeation,
      in vitro cytotoxicity, nasal clearance, in vivo bioavailability and brain uptake.
      In vivo bioavailability and brain uptake of ropinirole were assessed in albino
      rats following intranasal administration of 99mTc-ropinirole in situ gel,
      intranasal ropinirole solution and intravenous (i.v.) ropinirole solution.
      Radiolabeled ropinirole uptake was calculated as a fraction of administered dose.
      The absolute bioavailabilty of ropinirole from the temperature-mediated in situ
      gelling nasal formulation was 82%. The AUC (0-480 min) in brain after nasal
      administration of ropinirole in situ gel was 8.5 times (869 +/- 250% x min/g
      versus 102 +/- 20% x min/g) that obtained following i.v. administration, this
      value was also considerably higher (869 +/- 250% x min/g versus 281 +/- 52% x
      min/g) than that achieved with intranasal ropinirole solution. High brain direct
      drug transport percentage (DTP; 90.36%) and drug targeting index (DTI) > 1
      confirms direct nose to brain transport of the intranasal in situ gel formulation
      of ropinirole.

PMID- 20030504
TI  - Fluorobenzoyl dipeptidyl derivatives as inhibitors of the Fasciola hepatica
      cysteine protease cathepsin L1.
AB  - Cathepsins are known to have many important physiological roles and provide a
      viable target for inhibition. Fluorobenzoyl dipeptide derivatives were
      synthesized and tested for biological activity in an effort to find an efficient
      inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1
      36) were synthesized from protected amino acids via the standard DCC/HOBt
      coupling protocol, containing a benzyl ester or a nitrile as an electrophilic
      warhead. The activity of the inhibitors was evaluated against cathepsin L and
      IC50 values calculated. Modification of both amino acids and terminal groups
      afforded compounds with single digit micromolar inhibition. Results utilizing the
      benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the
      commercially available inhibitor 39.

PMID- 20030505
TI  - Stereoselective inhibition of butyrylcholinesterase by enantiomers of exo- and
      endo-2-norbornyl-N-n-butylcarbamates.
AB  - Enantiomers of exo- and endo-2-norbornyl-N-n-butylcarbamates were characterized
      as pseudo substrate inhibitors of butyrylcholinesterase. These inhibitions
      discriminate enantiomers of the inhibitors and therefore show stereoselectivity
      for the enzyme. For inhibitions by (R)-(+)- and (S)-(-)-exo-2-norbornyl-N-n
      butylcarbamates, R-enantiomer is a more potent inhibitor than S-enantiomer. But,
      for inhibitions by (R)-(+)- and (S)-(-)-endo-2-norbornyl-N-n-butylcarbamates, S
      enantiomer is a more potent inhibitor than R-enantiomer. Optically pure (R)-(+)
      exo-, (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norbornyl-N-n
      butylcarbamates were synthesized from condensations of optically pure (R)-(+)-exo
      , (S)-(-)-exo-, (R)-(+)-endo-, and (S)-(-)-endo-2-norborneols with n-butyl
      isocyanate, respectively. Optically pure norborneols were obtained from kinetic
      resolution of their racemic esters by lipase catalysis in organic solvent.

PMID- 20030506
TI  - Antibacterial and antifungal studies of macrocyclic complexes of trivalent
      transition metal ions with their spectroscopic approach.
AB  - A new series of complexes of the type [M(C24H16N4)X]X2, where M = Cr(III),
      Fe(III), and Mn(III), X = Cl-, NO3-, and CH3COO-, has been synthesized by
      template condensation of 1,8-diaminonaphthalene and glyoxal in the presence of
      trivalent metal salts in methanolic medium. The complexes have been characterized
      with the help of elemental analysis, conductance measurements, magnetic
      measurements, and electronic, NMR, IR, and mass spectral studies. On the basis of
      these studies, a five-coordinate square pyramidal geometry for all of these
      complexes has been proposed. All the synthesized metal complexes were also tested
      for their in vitro antimicrobial activities against some bacterial strains, viz.
      Bacillus subtilis, Bacillus stearothermophilus (gram-positive bacteria),
      Escherichia coli, and Pseudomonas putida (gram-negative bacteria), and some
      fungal strains, viz. Aspergillus flavus and Aspergillus niger. The results
      obtained were compared with standard antibiotics: chloramphenicol, streptomycin,
      and the antifungal drug cyclohexamide. Some of the tested complexes showed
      remarkable antimicrobial activities.

PMID- 20030507
TI  - Synthesis and leishmanicidal activity of 2,3,4-substituted-5-imidazolones.
AB  - Twenty-nine imidazolones 1-29 were synthesized and were randomly screened for
      their in vitro anti-leishmanial potential. Compound 17 showed a good anti
      leishmanial activity with an IC50 value of 12.98 +/- 0.32 microg/mL. Compounds 14
      and 24 were also found to be moderately active (IC50 values 28.20 +/- 0.03 and
      41.12 +/- 0.32 microg/mL, respectively). The activity was compared with that of
      standard drugs, amphotericin B (IC50 = 0.12 +/- 0.41 microg/mL) and pentamidine
      (IC50 = 2.56 +/- 0.10 microg/mL).

PMID- 20030508
TI  - Antioxidant activity of bisbenzylisoquinoline alkaloids from Stephania rotunda:
      cepharanthine and fangchinoline.
AB  - In the present study, we determined the antioxidant activity of cepharanthine and
      fangchinoline from Stephania rotunda by performing different in vitro antioxidant
      assays, including 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging,
      2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging,
      N,N- dimethyl-p-phenylenediamine dihydrochloride (DMPD) radical scavenging,
      superoxide anion (O2*-) radical scavenging, hydrogen peroxide scavenging, total
      antioxidant activity, reducing power, and ferrous ion (Fe2+) chelating
      activities. Cepharanthine and fangchinoline showed 94.6 and 93.3% inhibition on
      lipid peroxidation of linoleic acid emulsion at 30 microg/mL concentration,
      respectively. On the other hand, butylated hydroxyanisole (BHA), butylated
      hydroxytoluene (BHT), alpha-tocopherol, and trolox indicated inhibitions of 83.3,
      92.2, 72.4, and 81.3% on peroxidation of linoleic acid emulsion at the same
      concentration (30 microg/mL), respectively. According to the results,
      cepharanthine and fangchinoline have effective antioxidant and radical scavenging
      activity.

PMID- 20030509
TI  - Antimicrobial activities of some synthetic butenolides and their pyrrolone
      derivatives.
AB  - In the present investigation, 17 new synthetic butenolides, i.e. 2-arylidene-4-(4
      chloro/ethyl-phenyl)but-3-en-4-olides (3-19) have been synthesized from 3-(4
      chloro-benzoyl)propionic acid or 3-(4-ethyl-benzoyl)propionic acid using
      appropriate reagents. Some of the selected butenolides were reacted with ammonia
      and benzylamine to give the corresponding pyrrolones (20-31) and N-benzyl
      pyrrolones (32-39) respectively. All the compounds were screened for their
      antibacterial activity against Staphylococcus aureus, Escherichia coli, and
      Pseudomonas aeruginosa and antifungal activity against Candida albicans,
      Aspergillus niger, and Rhizopus oryza. Minimum inhibitory concentration (MIC)
      values of the compounds are reported. The pyrrolone derivatives discovered in
      this study may provide valuable therapeutic intervention for the treatment of
      microbial diseases, especially against fungal species.

PMID- 20030510
TI  - Cruzain inhibition by hydroxymethylnitrofurazone and nitrofurazone: investigation
      of a new target in Trypanosoma cruzi.
AB  - Nitrofurazone (NF) and its derivative, hydroxymethylnitrofurazone (NFOH), have
      presented antichagasic activity. NFOH has higher activity and lower mutagenicity.
      The aim of this work was to assess whether NF and its derivative NFOH would also
      be inhibitors of cruzain, besides their trypanothione reductase inhibitory
      activity. In vitro cruzain inhibition tests were performed for both compounds,
      and the 50% inhibitory concentration (IC50) for NF and NFOH presented values of
      22.83 +/- 1.2 microM and 10.55 +/- 0.81 microM, respectively. AM1 semi-empirical
      molecular modeling studies were performed to understand the activity of the
      compounds, corroborating the observed cruzain inhibitory activity.

PMID- 20030511
TI  - Synthesis of some imidazolyl-thioacetyl-pyrazolinone derivatives and their
      antinociceptive and anticancer activities.
AB  - In this study, some 4-(1,5-diarylimidazol-2-yl)thioacetyl-1-phenyl-2,3-dimethyl-3
      pyrazoline-5-one derivatives were prepared by reacting 4-(2-chloroacetyl)-1
      phenyl-2,3-dimethyl-3-pyrazoline-5-one and 2-mercapto-1, 5-diarylimidazole
      derivatives. The antinociceptive and anticancer activities of the compounds
      obtained were investigated. It was observed that some of the compounds, 2a, 2d,
      2g, and 2j, showed remarkable antinociceptive activity, and one of the compounds,
      2i, showed weak anticancer activity.

PMID- 20030512
TI  - New antihyperglycemic, alpha-glucosidase inhibitory, and cytotoxic derivatives of
      benzimidazoles.
AB  - Glycosidases play an important role in a wide range of physiological and
      pathological conditions, and have become potential targets for the discovery and
      development of agents useful for the treatment of diseases such as diabetes,
      cancer, influenza, and even AIDS. In this study, several benzimidazole
      derivatives were prepared from o-phenylenediamine and aromatic and heteroaromatic
      carboxaldehydes in very good yields, using PdCl2(CH3CN)2 as the most efficient
      catalyst. Synthesized compounds were assayed for their activity on yeast and rat
      intestinal alpha-glucosidase inhibition and cytotoxic activity against colon
      carcinoma cell line HT-29. Compound 3e exhibited 95.6% and 75.3% inhibition of
      yeast and rat intestinal alpha-glucosidase enzyme, while showing 74.8% cytotoxic
      activity against the HT-29 cell line at primary screening concentrations of 2.1
      mM for yeast and rat intestinal alpha-glucosidase enzyme and 0.2 mM for cytotoxic
      activity against the HT-29 cell line, respectively. Compound 3c displayed 76% and
      34.4% inhibition of yeast and rat intestinal alpha-glucosidase enzyme, and 80.4%
      cytotoxic activity against the HT-29 cell line at similar primary screening
      concentrations. The IC50 value for the most potent intestinal alpha-glucosidase
      inhibitor compound 3e was found to be 99.4 microM. The IC50 values for the most
      active cytotoxic compounds 3c and 3e were 82 microM and 98.8 microM,
      respectively. Both compounds displayed significant antihyperglycemic activity in
      starch-induced postprandial hyperglycemia in rats. This is the first report
      assigning yeast and rat intestinal alpha-glucosidase enzyme inhibition, cytotoxic
      activity against the HT-29 cell line, and antihyperglycemic activity to
      benzimidazole compounds 3c and 3e.

PMID- 20030513
TI  - DNA cleavage and in vitro antimicrobial studies of Co(II), Ni(II), and Cu(II)
      complexes with ONNO donor Schiff bases: synthesis, spectral characterization, and
      electrochemical studies.
AB  - A series of Co(II), Ni(II), and Cu(II) complexes of the type ML.2H2O have been
      synthesized with Schiff bases derived from 8-formyl-7-hydroxy-4-methylcoumarin
      and o-phenylenediamine/ethylenediamine. The structure of the complexes has been
      proposed in the light of analytical, spectral (IR, UV-Vis, ESR, and FAB-mass),
      magnetic, thermal, and fluorescence studies. The complexes are soluble in DMF and
      DMSO. The measured molar conductance values indicate that the complexes are non
      electrolytes in nature. In view of IR, UV-Vis, and magnetic studies, it has been
      concluded that all the complexes possess octahedral geometry, in which ligand is
      coordinated to metal ion through the azomethine nitrogen and phenolic oxygen via
      deprotonation. Thermal studies provide useful information about the coordination
      of water molecules to the metal ion and the stability of the complexes. The redox
      behavior of the complexes has been investigated by an electrochemical method
      using cyclic voltammetry. The Schiff bases and their metal complexes have been
      screened for their antibacterial (Escherichia coli, Staphylococcus aureus,
      Pseudomonas aeruginosa, and Salmonella typhi) and antifungal activities
      (Aspergillus niger, Aspergillus flavus, and Cladosporium) by the minimum
      inhibitory concentration method. DNA binding with Co(II) and Cu(II) complexes has
      been studied by the agarose gel electrophoresis method.

PMID- 20030514
TI  - Metabolite profile and in vitro activities of Phagnalon saxatile (L.) Cass.
      relevant to treatment of Alzheimer's disease.
AB  - The present study describes for the first time the in vitro properties
      (inhibition of NO production and anticholinesterase) of Phagnalon saxatile (L.)
      Cass. (Asteraceae). The methanolic extract showed antioxidant activity that was
      measured by DPPH assay and beta-carotene bleaching test. The same extract
      inhibited NO production in the murine monocytic macrophage cell line RAW 264.7.
      Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition was
      assessed by modifications of Ellman's method. Purification of the MeOH extract of
      P. saxatile allowed the isolation of phenolic compounds. Among them, the
      compounds that most effectively inhibited lipopolysaccharide-induced NO
      production were caffeic acid and methylchlorogenic acid, with IC50 values of 7
      microg/mL and 12 microg/mL, respectively. Luteolin and 3,5-dicaffeoylquinic acid
      exhibited the most promising activity against AChE with an IC50 of 25.2 and 54.5
      microg/mL, respectively, while caffeic acid and luteolin exhibited higher
      activity against BChE with an IC50 of 32.2 and 37.2 microg/mL, respectively.

PMID- 20030515
TI  - Trypanocidal activity of the ethyl esters of N-propyl and N-isopropyl oxamates on
      intracellular amastigotes of Trypanosoma cruzi acute infected mice.
AB  - In this investigation we studied the trypanocidal activity of the ethyl esters of
      N-propyl (Et-NPOX) and N-isopropyl (Et-NIPOX) oxamates on bloodstream
      trypomastigotes and on the clinically relevant intracellular amastigotes of
      Trypanosoma cruzi acute infected mice. In the infected and treated mice, the
      levels of parasitemia were drastically reduced between days 15 and 20 of
      treatment and almost to zero between days 35 and 40. We also found that Et-NPOX
      completely eliminated amastigote nests in the myocardium of mice infected with
      INC-5 or NINOA T. cruzi strain, and in skeletal muscle the reduction in the
      number of amastigote nests was between 60 and 80% in both strains. Also, Et-NIPOX
      reduced by 60-80% the number of amastigote nests in the myocardium and skeletal
      muscle of mice infected with these T. cruzi strains. In contrast, nifurtimox,
      used for comparison, produced a reduction of amastigote nests of only 20-40% in
      the studied tissues in both strains.

PMID- 20030516
TI  - Synthesis, structure, and antifungal evaluation of some novel 1,2,4
      triazolylmercaptoacetylthiosemicarbazide and 1,2,4-triazolylmercaptomethyl-1,3,4
      thiadiazole analogs.
AB  - Novel 1-[[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-yl]mercaptoacetyl]-4
      alkyl/aryl-3-thiosemicarbazides (5-12) were synthesized by the reaction of 4-(4
      bromophenyl)-5-(2-furyl)-4H-1,2,4-triazole-3-ylmercaptoacetylhydrazide (4) with
      substituted isothiocyanates. Cyclodehydration of thiosemicarbazides with
      concentrated sulfuric acid yielded 2-[4-(4-bromophenyl)-5-(2-furyl)-4H-1,2,4
      triazole-3-yl]mercaptomethyl-5-alkyl/arylamino-1,3, 4-thiadiazoles (13-17). The
      new compounds were evaluated for in vitro antifungal activity using the
      microdilution method. The tested compounds showed varying degrees of activity
      against Microsporum gypseum NCPF-580, Microsporum canis, Trichophyton
      mentagrophytes, Trichophyton rubrum, and Candida albicans ATCC 10231 (MIC 8-4
      microg/mL).

PMID- 20030517
TI  - Synthesis and activity of amides of tripeptides as potential urokinase
      inhibitors.
AB  - Eleven peptides of the general formula H-d-Ser-Ala-Arg-NH-X, where X = (CH2)n
      NH2, n = 2-9, (CH2)m-OH, m = 2-4, were obtained and tested for their effect on
      the amidolytic activities of urokinase, thrombin, trypsin, plasmin, t-PA, and
      kallikrein. H-D-Ser-Ala-Arg-NH-(CH2)5-NH2 inhibited urokinase with a Ki value of
      6.3 microM.

PMID- 20030518
TI  - New antioxidant flavonoid isolated from Leuzea carthamoides.
AB  - A new natural flavonoid patuletin 3'-beta-xylofuranoside was isolated from Leuzea
      carthamoides leaves. The antioxidant activity of this compound was evaluated by
      the DPPH radical assay and ferric reducing antioxidant power (FRAP) assay, and
      the results were compared with those for trolox and quercetin. DPPH radical
      scavenging activity of the tested compounds was expressed by the parameter EC50:
      patuletin 3'-beta-xylofuranoside (56.0 microM), trolox (27.8 microM), and
      quercetin (25.3 microM). The ferric reducing activity of the compounds was
      demonstrated as FRAP values at 4 and 60 min: patuletin 3'-beta-xylofuranoside
      (28.4 microM, 35.8 microM), trolox (19.3 microM, 20.2 microM), and quercetin
      (54.3 microM, 79.9 microM). The structure/activity relationship of the flavonoid
      is also discussed. The results indicate significant antioxidant potency of
      patuletin 3'-beta-xylofuranoside.

PMID- 20030519
TI  - Incidence of fever of unknown origin and subsequent antitubercular medications in
      hemodialysis patients: a two-year prospective study.
AB  - BACKGROUND: Hemodialysis (HD) patients are susceptible to atypical tuberculosis
      (TB), especially among patients presenting with fever of unknown origin (FUO),
      because of their impaired cellular immunity. Diagnostic trials of anti-TB drugs
      are therefore recommended in some TB endemic countries, including Japan, though
      clinical evidence for this therapy is scarce. METHODS: We prospectively collected
      data for incident cases of clinical FUO for two years in 78 of 169 dialysis
      facilities in Aichi prefecture, located in central Japan. Clinical FUO was
      defined as sustained fever without any localizing signs and no infiltration on
      chest x-rays after a one-week antibiotic trial. The baseline characteristics,
      subsequent body temperatures on the days of HD therapy, and names of antibiotics
      including anti-TB drugs with the durations of medication were reported until
      fever alleviation or fever sustainment for over eight weeks. RESULTS: We
      identified 15 newly developed clinical FUO patients among 8,125 HD patients. The
      incidence rate was estimated to be 92 (95% CI, 26-158) per 100,000 person-years.
      This corresponds to 244 cases per year among 264,473 HD patients in Japan. Anti
      TB drugs were secondarily prescribed in 8 of 15 clinical FUO patients (53%). No
      improved fever alleviation was observed when anti-TB drugs were secondarily
      prescribed compared with cases in which other antibiotics were preferred.
      CONCLUSION: We investigated the incidence of FUO in HD patients and found that
      the rate was not very high, whereas anti-TB drugs were frequently used for FUO
      cases. The efficacy of this diagnostic therapy should be elucidated in large
      scale studies.

PMID- 20030520
TI  - Anemia development and cardiovascular risk management in nonanemic stage 3
      chronic kidney disease.
AB  - BACKGROUND/AIM: There is little information on the development of anemia in the
      early stages of chronic kidney disease. The aim of this study was to analyze the
      onset of renal anemia in a cohort of initially nonanemic chronic kidney disease
      patients followed up in nephrology clinics. METHODS: This epidemiological,
      prospective, three-year, multicenter study enrolled patients aged 18-78 years
      with stage 3 chronic kidney disease without anemia. Interim analysis was
      performed on the data collected during the first 12 months. RESULTS: The study
      included 432 patients, average age 63.6 years (range 22-78 years, 70% male). The
      main etiologies of chronic kidney disease were glomerular (11.6%), interstitial
      (10.4%), vascular (29.4%), and diabetic (16.9%). The percentages of patients with
      comorbidities were 33.8% diabetes (2.5% type 1), 69% dyslipidemia, and 93%
      hypertension. During the first year, 12.4% of patients developed anemia. The
      chronic kidney disease progression rate was low: proteinuria was 0.46 +/- 0.8
      g/24 h at one year versus 0.67 +/- 1.0 g/24 h at baseline. Diabetic patients
      showed a greater prevalence of previous cardiovascular events (50.0% vs. 24.5%)
      and worse control of some modifiable cardiovascular risk factors: smoking (13.4%
      vs. 8.6%), obesity (BMI > 30 kg/m(2), 33.6% vs. 25.3%), target blood pressure
      (<130/80 mmHg, 21.0% vs. 27.9%), and proteinuria (0.8 +/- 1.1 vs. 0.6 +/- 0.9
      g/day). CONCLUSIONS: After one year, 12.4% of patients developed anemia. Diabetic
      patients had a higher cardiovascular risk and limited blood pressure control. The
      overall control of cardiovascular risk was unsatisfactory.

PMID- 20030521
TI  - Type of renal replacement therapy and residual renal function may affect
      prohepcidin and hepcidin.
AB  - Hepcidin is a small defensin-like peptide, the production of which by hepatocytes
      is modulated in response to anemia, hypoxia, or inflammation. Kidneys are
      involved in not only the synthesis of hepcidin, but they also may be involved in
      its elimination. A cross-sectional study was performed to assess prohepcidin and
      hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to
      type of renal replacement therapy and prohepcidin and hepcidin correlations with
      renal function, iron status, and markers of inflammation. METHODS: Prohepcidin
      and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using
      commercially available kits in 102 patients on hemodialyses, 17 on
      hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers. RESULTS:
      In hemodialyzed and peritoneally dialyzed patients with residual renal function,
      serum prohepcidin (264.21 +/- 95.84 vs. 341.84 +/- 90.45 ng/mL, p < 0.01; 142.76
      +/- 57.87 vs. 238.42 +/- 84.32 ng/mL, p < 0.01, respectively) and hepcidin
      (178.89 +/- 89.87 vs. 295.76 +/- 129.65 ng/mL, p < 0.01; 108.43 +/- 75.49 vs.
      186.53 +/- 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in
      anuric patients. In peritoneal effluent, prohepcidin level was significantly
      higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis,
      residual renal function, ferritin, and hsCRP were predictors of hepcidin in
      hemodialyzed patients, while residual renal function and ferritin were predictors
      of hepcidin in peritoneally dialyzed patients. CONCLUSIONS: Residual renal
      function seems to play a pivotal role in hepcidin levels in dialyzed patients. In
      addition, the presence of low-grade inflammation, more pronounced in anuric
      patients, and functional iron deficiency may also contribute to the elevated
      hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may
      partially explain its lower concentration in peritoneal dialysis and
      hemodiafiltration.

PMID- 20030522
TI  - Urine volume in acute kidney injury: how much is enough?
AB  - Eight hundred and seventy-nine patients with acute kidney injury were
      retrospectively studied over year and eleven months for evaluation of urine
      volume as a risk factor for death. They were divided into five groups, according
      to the 24 h urine volume (UV): anuric (UV <or= 50 mL/24 h, group 1), oliguric (UV
      > 50 mL/24 h and < 400 mL/24 h, group 2), and non-oliguric (UV >or= 400 mL/24 h).
      Nonoliguric group was subdivided in three subgroups: UV > 400 mL/24 h and <or=
      1000 mL/24 h (group 3, reference group), UV > 1000 mL/24 h and <or= 2000 mL/24 h
      (group 4), and UV > 2000 mL/24 h (group 5). Linear tendency test (Mantel
      extension) pointed out a significant increase in mortality with UV decrease (p <
      0.001), confirmed by multivariate analysis. Anuric and oliguric patients had
      increased risk of respectively 95% and 76% times for death compared to controls
      (p < 0.05). Patients from groups 4 and 5 presented a reduced risk for death of
      50% and 70%, respectively, p = 0.004 and p = 0.001. In conclusion, urine volume
      was a strong independent factor for mortality in this cohort of AKI patients.

PMID- 20030523
TI  - Prevalence of hyperkalemia among hemodialysis patients in Egypt.
AB  - INTRODUCTION: Hyperkalemia is a frequent problem in patients with end stage renal
      disease (ESRD) on maintenance hemodialysis and is often attributed as a cause of
      deaths in these patients. The aim of this study was to estimate the prevalence of
      hyperkalemia among Egyptian hemodialysis patients. PATIENTS AND METHODS: 400 ESRD
      patients on maintenance hemodialysis were enrolled in the study. They were
      allowed their usual diets and medications during the study periods. For all
      patients, history and clinical examinations and serum potassium level was
      measured three times--pre- and post-1st session and pre-next session--at two
      successive sessions of hemodialysis. RESULTS: The results of this study showed
      that the prevalence of hyperkalemia was 41.2%, 6.5%, and 66.9% of pre- and post
      dialysis and before the next session of dialysis, respectively. Hyperkalemia
      significantly correlates with potassium-rich diets, non-compliant patients, two
      sessions of hemodialysis per week, and constipation in ESRD patients during the
      study periods. Serum potassium level was significantly higher in anuric ESRD
      patients than those who had residual renal function, patients using acetate
      dialysate than those using bicarbonate dialysate, and patients with low blood
      flow rate than those with higher blood flow rates. There was a non-significant
      correlation between serum potassium and ACEls, B-blockers, or diabetes.
      CONCLUSION: Hyperkalemia is a frequent problem in patients with end stage renal
      disease in Egypt. Hyperkalemia significantly correlates with a potassium-rich
      diet and inadequate dialysis either by prescription or non-compliance. Thrice
      weekly bicarbonate dialysis with higher blood pump flow rate had better
      elimination of potassium.

PMID- 20030524
TI  - Effects of ureteral stent on urologic complications in renal transplant
      recipients: a retrospective study.
AB  - The aim of the present study was to analyze the effects of ureteral stents used
      in renal transplantation on urologic as well as other complications. Cases of
      renal transplants from living or deceased donors performed in our hospital were
      retrospectively evaluated. The effects of the routine use of ureteral stents on
      postoperative complications were investigated. All outcomes and complications
      encountered during the postoperative follow-up were recorded. The Lich-Gregoire
      technique, which is a method of extravesical ureteroneocystostomy, was performed
      on all patients. One hundred and twenty-two patients underwent renal
      transplantation between 2001 and 2007 in our hospital. Stents were placed
      routinely in all patients. Leakage was observed in one patient, and one patient
      developed an obstruction; however, none of the patients developed an infection. A
      lymphocele developed in one patient. All urologic complications were treated
      without major morbidity. Graft loss did not occur. Complications following
      urinary anastomosis have a high rate of morbidity in renal transplantation.
      Ureteral stenting in renal transplant recipients prevents early urologic
      complications. The data generated in the current study were compared to the
      literature.

PMID- 20030525
TI  - A study on the protection of hemodialysis patients against diphtheria and
      tetanus.
AB  - Patients with end stage renal disease suffer from a high incidence of infectious
      diseases believed to be related to their impaired immune system. To determine the
      antitetanus and antidiphtheria IgG antibody levels in Iranian hemodialysis
      patients with end stage renal disease, as well as its association with sex, age,
      hemoglobin, zinc serum level, serum albumin, duration of dialysis, number of
      dialysis per week, dialysis adequacy, erythropoietin or iron supplements such as
      venofer, body mass index (BMI), and underlying renal disorder, we conducted a
      cross-sectional study on a total of 112 hemodialysis patients with end stage
      renal disorder (60 male, 52 female ) and 36 healthy individuals in the control
      group (14 male, 22 female). The patients and the control group received no
      antitetanus or antidiphtheria vaccine or immunoglobulin in the year prior to the
      investigation. The serum antitetanus and antidiphtheria IgG antibody levels were
      measured using the ELISA method. We found out that only 16% of our hemodialysis
      patients were immune to diphtheria (19% of the control group), and this rate for
      tetanus was 24% (48.2% in the healthy control). Except for the hemodialysis
      duration, none of the mentioned factors seemed to affect immunity. We conclude
      that in our study, the level of the antitetanus IgG antibody (unlike the
      antidiphtheria IgG antibody level) is significantly different among the
      hemodialysis patients, the chronic hemodialysis patients, and the control group.

PMID- 20030526
TI  - Urinary and serum biomarkers after cardiac catheterization in diabetic patients
      with stable angina and without severe chronic kidney disease.
AB  - BACKGROUND/AIMS: Different serum and urinary biomarkers have been recently
      proposed to serve as markers of acute kidney injury. We tested the hypothesis
      whether NGAL and other biomarkers could represent an early biomarker of contrast
      nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing
      cardiac catheterization in comparison with non-diabetic patients. METHODS: Serum,
      urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin
      18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated
      before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using
      commercially available kits. RESULTS: In both groups we found a significant rise
      in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8,
      and 24 hours after cardiac catheterization. Serum cystatin C increased
      significantly 8 hours, reaching peak 24 hours after cardiac catheterization in
      both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase
      significantly after 24 and 48 hours after cardiac catheterization. CONCLUSIONS:
      CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing
      cardiac catheterization. NGAL seems to be a potential early marker for
      nephrotoxicity and predictor of contrast nephropathy. It is particularly
      important in the upcoming setting of short-time hospitalizations for cardiac
      catheterization.

PMID- 20030527
TI  - Prevalence of chronic kidney disease in the Black Sea Region, Turkey, and
      investigation of the related factors with chronic kidney disease.
AB  - We aimed to assess the prevalence of CKD in the Black Sea Region, Turkey, and to
      evaluate any relationship between age, gender, diabetes, obesity, hypertension,
      and CKD. This study was conducted in 70 different areas in Tokat Province in the
      Black Sea Region, in the northern part of Turkey. The estimated glomerular
      filtration rate (eGFR) was calculated from the serum creatinine using MDRD
      formulas. CKD-defined estimated GFR was lower than 60 mL/min/1.73 m(2). A total
      of 1,079 persons were included in this study (mean age 41.4+/-17 years [range: 18
      95 years], 49.4% males, 50.6% living in an urban area). Of the 1,079 individuals,
      5.28% were diabetic, 22.9% were obese, and 37.8% were hypertensive. CKD was found
      in 62 of them (5.75%). The prevalence of CKD was 5.58% in non-diabetics and 8.77%
      in diabetics. No significant differences were found between two groups. The
      prevalence of CKD was 3.77% in non-hypertensive individuals and 8.82% in
      hypertensive patients, and 4.46% in non-obese and 9.31% in obese. The evident
      significant differences were found between groups (p < 0.0001 and p = 0.004,
      respectively). The prevalence of CKD increased with age within our population. A
      salient observation was the markedly higher prevalence of CKD in females than
      males (p = 0.046). There was an inverse correlation between eGFR and age (r =
      0.529, p < 0.0001). The overall prevalence of CKD was 5.75% in general
      population. The prevalence of CKD increased with age within our population. Age,
      gender, obesity and hypertension were found to be significant risk factors for
      development of CKD in our population.

PMID- 20030528
TI  - Effect of spironolactone on urinary protein excretion in patients with chronic
      kidney disease.
AB  - AIM: To investigate antiproteinuric effect of spironolactone in patients with
      chronic kidney disease (CKD) treated with angiotensin-converting enzyme (ACE)
      inhibitors and/or angiotensin II type 1 receptor blockers (ARBs). METHODS: This
      study was performed in 33 CKD patients with proteinuria. 24 h urinary protein
      excretion and biochemical parameters were obtained before the therapy. Then,
      spironolactone (25 mg/d) was added to the therapy. The antiproteinuric effect of
      spironolactone was examined for eight weeks. RESULTS: At eight weeks, there was a
      significant decrease in proteinuria (p < 0.001, 47.9% decrease). Systolic and
      diastolic blood pressures were significantly decreased (p < 0.004, p < 0.001,
      respectively). However, no correlation was detected between the reductions in
      systolic and diastolic BP and the reduction in proteinuria (p = 0.464, p = 0.239,
      respectively). Serum potassium level increased significantly (p < 0.001).
      CONCLUSIONS: Our study suggests that spironolactone significantly reduces urinary
      protein excretion. This strategy may be useful to slow the progression of CKD.
      However, hyperkalemia is the most important side effect of treatment, and it is
      necessary to monitor potassium level. Further studies are needed to determine the
      efficacy of spironolactone on proteinuria.

PMID- 20030529
TI  - Factors related to silent myocardial damage in hemodialysis patients.
AB  - BACKGROUND: Both traditional and non-traditional risk factors play a role for the
      development of cardiovascular disease in hemodialysis patients. However, a
      specific relationship between these risk factors and silent myocardial damage is
      unknown. METHODS: Demographic, anthropometric, clinical, and laboratory data were
      collected. Silent myocardial damage was defined by elevated cardiac troponin I
      values above cutoff values. RESULTS: In total, 113 hemodialysis patients were
      included. Cardiac troponin I concentrations were below cutoff value (<2.3 ng/mL)
      in 103 (91.2%) patients (Group 1), whereas 10 (8.8%) patients had elevated
      concentrations (Group 2). Group 1 patients had higher levels of hemoglobin (p =
      0.002) and high-density lipoprotein cholesterol (p = 0.002) and lower C-reactive
      protein (p = 0.003) and tumor necrosis factor-alpha (p = 0.005) levels, as well
      as less incidence of left ventricular hypertrophy (p = 0.045), when compared to
      Group 2 patients. Diabetes mellitus (Beta = +0.160, p = 0.021), left ventricular
      hypertrophy (Beta = +0.247, p < 0.0001), uncontrolled blood pressure (Beta =
      +0.170, p = 0.016), normalized protein equivalent of total nitrogen appearance
      (Beta = -0.230, p = 0.001), hemoglobin (Beta = -0.302, p < 0.0001), and tumor
      necrosis factor-alpha (Beta = +0.506, p < 0.0001) were found to be independently
      associated with cardiac troponin I levels in multiple linear regression analysis.
      CONCLUSIONS: Both traditional and non-traditional risk factors are related with
      silent myocardial damage, which is considered to an antecedent of major
      cardiovascular events. Hemodialysis patients, even when asymptomatic, must be
      closely followed up for the presence of these risk factors.

PMID- 20030530
TI  - Renin-angiotensin system blockade is not associated with hyperkalemia in chronic
      hemodialysis patients.
AB  - BACKGROUND: Serious hyperkalemia was reported in 10% of chronic hemodialysis (HD)
      patients that could lead to arrhythmia and death. Angiotensin-converting enzyme
      inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) are well accepted
      for cardio-protective benefits. The relationship between renin-angiotensin system
      blockade (RASB) and hyperkalemia in chronic HD patients remains controversial.
      The aim of this study was to find the relationship between RASB and hyperkalemia
      in these patients. METHODS: Pre-dialysis serum potassium, clinical factors, and
      drugs were evaluated in 200 chronic HD patients in one HD center. Hyperkalemia
      was defined as serum K >or= 5.3 meq/L. Finally, multivariate analysis with
      logistic regression was used to evaluate the risk of hyperkalemia by RASB and
      other factors. RESULTS: In 200 patients, the mean K was 4.93 +/- 0.79 meq/L, and
      70 (35%) patients had hyperkalemia. Fifty-eight (29%) patients were prescribed
      with RASB. Seven variables--non-DM, longer HD duration, lower dialysate calcium,
      lower serum glucose, higher serum iPTH, not using RASB, and not using furosemide-
      were more frequent in hyperkalemia group. In logistic regression analysis, RASB
      was associated with decreased odds for hyperkalemia (OR 0.262, p = 0.001 in model
      A; OR 0.205, p = 0.001 in model B). In addition, furosemide was associated with
      decreased odds for hyperkalemia (OR 0.068, p = 0.022 in model B). CONCLUSIONS:
      RASB is not associated with hyperkalemia in chronic HD patients.

PMID- 20030531
TI  - Expression of augmenter of liver regeneration in rats with gentamicin-induced
      acute renal failure and its protective effect on kidney.
AB  - Augmenter of liver regeneration (ALR) enhances the proliferation of hepatocytes
      and accelerates recovery from acute liver failure in animal models. ALR is
      expressed in both the liver and kidney; however, the specific location of ALR
      expression and its biological effects in the kidney remain unknown. We aimed to
      investigate the efficacy of ALR in rats with gentamicin (GM)-induced acute renal
      failure (ARF). Rats were randomized into the normal group, GM+saline group,
      GM+vehicle group, and GM+rrALR group. Blood urea nitrogen, serum creatinine, and
      urine beta-N-acetyl-D-glucosaminidase were measured, and histological analyses of
      the kidneys were performed. The expression of ALR protein was determined by
      immunohistochemistry and Western blotting. In vitro incorporation of tritiated
      thymidine was used to measure the proliferation of renal tubular epithelial
      cells. In normal rats, the expression of ALR protein was faint in the medulla and
      absent in the cortex. However, in ARF rats, ALR expression increased
      significantly in both the renal cortex and medulla. Histological analyses
      revealed that treatment with recombinant rat ALR (rrALR) reduced the extent of
      injury of tubular cells in the renal cortex. Serum/urine biochemical parameters
      also showed that renal dysfunction was improved by the administration of rrALR.
      Intraperitoneal injection of rrALR enhanced the proliferation of tubular cells in
      vivo. We also confirmed that rrALR could promote the proliferation of renal
      tubular cells in vitro. These results indicate that rrALR effectively accelerates
      kidney recovery after ARF induced by gentamicin, and that the protective effect
      is associated with enhanced proliferation of renal tubular cells.

PMID- 20030532
TI  - Evaluation of gadolinium pre-treatment with or without splenectomy in the setting
      of renal ischemia reperfusion injury in rats.
AB  - INTRODUCTION: This study aims to investigate gadolinium chloride (Gd) pre
      treatment with/without splenectomy (Splx) in the setting of renal
      ischemia/reperfusion (IR) injury in rats. MATERIALS AND METHODS: Under
      anesthesia, male Wistar albino rats with or without splenectomized (Splx) were
      right nephrectomized and subjected to 45 min of renal pedicle occlusion followed
      by 3 h of reperfusion. Gadolinium chloride (10 mg kg(-1)) or saline was
      administered 24 hours prior to ischemia via penile vein. Right nephrectomy and
      intravenous saline administration was performed in the control group. At the end
      of the reperfusion period, following decapitation, kidney samples were taken for
      histological examination or determination of renal malondialdehyde (MDA) and
      glutathione (GSH) levels and myeloperoxidase (MPO) and Na(+)-K(+) ATPase
      activities. Creatinine, blood urea nitrogen (BUN), lactate dehydrogenase (LDH),
      TNF-alpha, and IL-1 beta were assayed in the serum samples. RESULTS:
      Ischemia/reperfusion caused significant increases in the serum TNF-alpha, IL-1
      beta, BUN, creatinine, AST, ALT, LDH, and tissue MDA levels and MPO activity,
      while either Gd pre-treatment or Splx decreased these parameters significantly.
      On the other hand, IR induced a decrease in the tissue GSH, and Na(+)-K(+) ATPase
      activity was restored by both gadolinium and Splx. Furthermore, histopathological
      alterations induced by IR were also reversed. CONCLUSION: The extent of renal IR
      injury depends on the pro-inflammatory cytokine response. Gd pre-treatment
      decreases macrophage-derived cytokine secretion and thereby effectively limits
      the extent of renal IR injury in rats similar to Splx. Further studies needed to
      define an optimal way of decreasing macrophage-derived cytokine release due to
      the clinical limitations of Gd.

PMID- 20030533
TI  - Effect of the absence of interleukin-12 on mesangial proliferative
      glomerulonephritis induced by habu snake venom.
AB  - BACKGROUND: Interleukin-12 (IL12) participates in the pathophysiology of various
      experimental types of progressive glomerulonephritis, but its role in acute
      mesangial glomerulonephritis (AMG) induced by habu snake venom (HSV) has not been
      determined. This study aims to evaluate the effect of the absence of IL12 on AMG
      induced by HSV. METHODS: AMG was induced in IL12 knockout (IL12-/-) and C57Bl/6
      (IL12+/+) mice by a single i.v. administration of HSV. Vehicle was used in
      control animals. Mice were studied after 3, 7, and 14 days (D3, D7, and D14).
      RESULTS: After treatment with HSV, IL12+/+ and -/- mice developed focal
      glomerular lesions, but groups of both lineages showed no statistical difference
      concerning albuminuria, serum creatinine, histopathology, number of cells by
      glomerular tuft, and glomerular tuft area. Compared to IL12+/+ mice, IL12-/- mice
      showed lower scores of glomerular desmin expression on D7 [1.55 (1.32; 1.65) vs.
      1.12 (1.07; 1.22); p < 0.01] and D14 [1.60 (1.55; 1.75) vs. 1.20 (1.15; 1.20); p
      < 0.001], respectively, and lower scores of glomerular alpha-SMA expression on
      D14 [0.30 (0.21; 0.38) vs. 0.16 (0.26; 0.36); p < 0.001], respectively.
      CONCLUSION: The absence of IL12 reduced the activity of mesangial cells, but did
      not modify the course of HSV-induced AMG in mice.

PMID- 20030534
TI  - Apart from the other members of PDE inhibitors' family, enoximone does not
      enhance renal ischemic reperfusion injury: the effects of enoximone on renal
      ischemia reperfusion.
AB  - Many pharmacological agents were investigated for the prevention of renal
      ischemic reperfusion (IR) injury as well as the phosphodiesterase (PDE)
      inhibitors. The aim of the study was to examine the possible renoprotective
      effect of enoximone as a member of this family on IR injury. Thirty-six Wistar
      Albino rats were allocated to six groups. Sham (S) and control groups (E1, E2)
      only received 0.09% NaCl, 5 mg/kg and 10 mg/kg enoximone via caudal caval vein,
      respectively. In ischemia (I) and treatment groups (IE1, IE2), the rats were
      subjected to bilateral renal artery occlusion and were given 0.09% NaCl, 5 mg/kg
      and 10 mg/kg enoximone in the same route, respectively. Bilateral kidneys were
      removed at the sixth hour of laparotomy for histopathological and biochemical
      analysis, such as superoxide dismutase, myeloperoxidase, malonyldialdehyde, and
      nitric oxide end products. Blood samples were taken in order to evaluate renal
      function tests. The data were analyzed by using one-way analysis of variance, and
      p < .05 was considered to be statistically significant. The worst results were
      achieved in ischemia group (p < .05). Treatments groups showed nearly similar
      findings with this group (p < .05). There was no significant difference between
      control and sham groups. In this study, we found that apart from the other
      members of the PDE inhibitors' family, enoximone did not contribute to the
      attenuation of IR injury of kidney.

PMID- 20030535
TI  - Pancreatic injury in rabbits with acute renal failure.
AB  - BACKGROUND: Acute renal failure (ARF) is a common critical disorder. To decrease
      the mortality, it is important to prevent ARF from invading other organs in
      clinical setting. It is not known whether there is a dysfunction in pancreas
      during the pathogenesis of ARF. This study aimed to investigate the changes of
      morphology and function on pancreas in ARF rabbits. METHODS: Sixty rabbits were
      randomly divided into four groups. The ARF model of groups 1 and 2 rabbits was
      established by hypodermic injection of 1% HgCl(2) (1.3 mL/kg) and intramuscular
      injection of 50% glyceritum (10 mL/kg), respectively. The control groups 1 and 2
      were injected with same volume of normal saline. After 24 hours, urea and
      creatinine contents and pancreatic amylase (AMY) activities in serum were
      measured using an automatic biochemical analyzer; the insulin levels were
      measured with radioimmunoassay method. Moreover, morphological alterations were
      examined by light microscopy; free radicals, nitric oxide (NO), and nitric oxide
      synthase (NOS) in pancreas homogenate were determined. RESULTS: Morphological
      study showed that there were vacuolar degeneration and necrosis in pancreas of
      ARF for both groups 1 and 2. Compared with corresponding control group, the AMY
      activity was significantly elevated, whereas the INS values were decreased
      significantly in ARF groups 1 and 2. Malonaldehyde, NO, and NOS in pancreas
      homogenate were significantly increased, and superoxide dismutase activity was
      decreased. CONCLUSION: These data suggested that there were morphological damage
      of pancreas and disturbance of pancreatic secretion function in rabbits with ARF.
      Free radicals-injury and NO excessive release may explain the observed
      dysfunction.

PMID- 20030536
TI  - Transplant renal artery stenosis associated with acute cytomegalovirus infection:
      resolution following ganciclovir administration.
AB  - Cytomegalovirus has been implicated in the pathogenesis of transplant renal
      artery stenosis. However, the clinical course of this infection-associated
      transplant renal artery stenosis and its response to antiviral treatment is still
      unclear. We report a patient with transplant renal artery stenosis associated
      with an acute cytomegalovirus infection, which resolved following ganciclovir
      administration without the need for surgical or angiographic intervention.
      Serological testing revealed positive titers of anti- cytomegalovirus IgM and IgG
      antibodies. Renal allograft Doppler study findings were compatible with critical
      renal artery stenosis. Renal allograft angiography disclosed a critical circular
      stenosis. Following the intravenous ganciclovir administration, dramatically
      decreased Doppler ultrasound parameters along with the absence of parvus/tardus
      waveform pattern revealed the resolution of the stenosis. Moreover, the
      serological testing was negative for anti-cytomegalovirus IgM antibody, but anti
      cytomegalovirus IgG antibody was positive. This report not only implies the
      causative possible relationship between acute cytomegalovirus infection and
      transplant renal artery stenosis, but it also highlights the importance of this
      complication when managing a renal transplant recipient with signs of allograft
      arterial stenosis.

PMID- 20030537
TI  - The crosstalk between physiology and circadian clock proteins.
AB  - In mammals, many physiological processes present diurnal variations, and most of
      these rhythms persist even in absence of environmental timing cues. These
      endogenous circadian rhythms are generated by intracellular timing mechanisms
      termed circadian clocks. In mammals, the master clock is located in the
      suprachiasmatic nuclei (SCN), but other brain regions and most peripheral tissues
      contain circadian clocks. These clocks are responsive to environmental cues, in
      particular light/dark and feeding/fasting cycles. In the last few years, tissue
      specific knock-out and transgenic mouse models have helped to define the
      physiological roles of specific clocks. Recent reports indicate that the clock
      physiology connection is bi-directional, and physiological cues, in particular
      the energetic status of the cell, can feed into the clockwork. This effect was
      discovered unexpectedly in molecular analyses of clock protein modifications.
      Beyond the positive and negative transcription/translation feedback loops of the
      molecular oscillator lies another level of complexity. Post-translational
      modifications of clock proteins are both critical for the timing of the clock
      feedback mechanism and to provide regulatory fine-tuning. This review summarizes
      recent advances in our understanding of the roles of peripheral clocks and of
      post-translational modifications occurring on clock proteins. These two matters
      are at the intersection of physiology, metabolism, and the circadian system.

PMID- 20030538
TI  - Expression profiling reveals a positive regulation by mPer2 on circadian rhythm
      of cytotoxicity receptors: Ly49C and Nkg2d.
AB  - The mammalian circadian gene, mPer2, an indispensable component of the mammalian
      circadian clock, not only modulates endogenous circadian rhythms but also plays a
      crucial role in regulating innate immune function. Previously, we showed that
      mPer2 plays a crucial role in regulating cytotoxic response. To investigate the
      molecular mechanism for mPer2-controlled cytotoxic response, in the present study
      we conducted mRNA expression for 11 genes participating in cytotoxicity
      regulation in wild-type (WT) and mPer2 knockout (mPer2(-/-)) mice bone marrow,
      that is, Dap-10, Ly49C, Ly49I, Rac1, Mapk1, Map2k1, Nkg2d, Shp-1, Pak1, Pik3ca,
      and Vav1. The mRNA levels of Ly49C (p < 0.001), Ly49I (p = 0.039), and Nkg2d (p =
      0.038) were significantly downregulated in mPer2(-/-) mice. Time-dependence of
      expression profiling was then conducted for four core clock genes (Per1, Bmal1,
      Clock, Rev-erbalpha), and six out of these 11 cytotoxic regulation genes (Ly49C,
      Ly49I, Mapk1, Nkg2d, Shp-1, Pik3ca) in WT and mPer2(-/-) entrained in light/dark
      (LD) or dark/dark (DD) cycles. Consistently, circadian oscillations were observed
      for Per1, Rev-erbalpha, Ly49C, and Nkg2d in WT mice under LD and DD cycles.
      However, these rhythmic expressions were either disrupted or dampened in mPer2(-/
      ) mice. Comparison of gene expression between WT and mPer2(-/-) mice showed that
      mPer2 knockout had systematically downregulated the mRNA expression of two
      cytotoxicity regulators, Ly49C and Nkg2d. FACS analysis further confirmed that
      the circadian expression of these genes was not due to the daily difference in
      cell numbers of NK, NKT, or T cells in bone marrow. Taken together, our results
      reveal that mPer2 is a critical clock component in modulating circadian rhythms
      in bone marrow. Furthermore, it implies that Ly49C and Nkg2d are two clock
      controlled genes that may play an important role in mediating mPer2-controlled
      cytotoxic response.

PMID- 20030539
TI  - Early programming of astrocyte organization in the mouse suprachiasmatic nuclei
      by light.
AB  - The principal pacemaker in mammals, controlling physiology and behavior, is
      located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Early photic
      experience has long-term effects on the animal's rhythmic behavior, as indicated
      by alterations in the phase shift induced by a light pulse, and in the expression
      of the circadian rhythm of locomotor activity under light-dark (LD), constant
      light (LL), and constant darkness (DD) environments. However, the brain
      substrates targeted by early light have not yet been identified. Possible
      candidates are astrocytes, as they develop postnatally in parallel to the
      circadian system, and are involved in SCN function by modulating intercellular
      communication and mediating photic input. Here, we reared three groups of mice
      under different light environments (LD, LL, and DD) during the suckling period.
      Later on, all mice were entrained to LD, and we determined associated astrocytic
      modifications by examining the expression of glial fibrillary acidic protein
      (GFAP) in the SCN. We observed that although LL-reared mice showed lowest GFAP
      expression in the SCN, as determined by quantification of immunostaining levels,
      the number of GFAP-positive cells was highest in this group, suggesting
      structural remodelling of SCN astrocytes by early light experience. These results
      indicate the postnatal light environment has long-term effects on the astrocytic
      population of the SCN. We argue that these neurochemical and structural
      alterations may affect clock function, which may in turn modify animal behavior

PMID- 20030540
TI  - Response of melatonin receptor MT1 in spleen of a tropical Indian rodent,
      Funambulus pennanti, to natural solar insolation and different photoperiodic
      conditions.
AB  - We analyzed the effect of natural solar insolation and artificial photoperiodic
      conditions on melatonin MT1 receptor expression of a tropical rodent, Funambulus
      pennanti. Melatonin mediates reproductive and circadian responses and regulates
      the production of a large number of cytokines, including interleukin-2 (IL-2),
      via modulation of MT1 receptor expression. Maximum pineal activity, resulting in
      high melatonin level, low melatonin receptor expression, and increased splenic
      mass, was noted in the winter months, while an opposite effect was noted during
      the summer months. Further, constant light exposure mimicked an "enhanced summer"
      like condition with significant hyposplenia, and an opposite effect was observed
      with constant dark exposure with significant splenomegaly in F. pennanti. In the
      annual study, a slight increase in melatonin level was noted during the monsoon
      period, when the duration of photoperiod was the same but the amount of solar
      insolation and direct radiation decreased. The present study found that not only
      the duration of natural sunlight (i.e., photoperiod) but the intensity of
      sunlight expressed by solar insolation affects the circulatory level of melatonin
      and melatonin receptor expression in this wild tropical rodent. An increase in
      the circulatory level of melatonin induced a decrease in its receptor subtype MT1
      expression in splenic cells, both at the transcriptional and translational
      levels, thus reflecting autoregulatory down-regulation of melatonin receptors.
      Therefore, in our animal model, F. pennanti melatonin may be suggested as a
      molecular messenger of photoperiodic signals (duration and intensity) directly
      acting via MT1 receptor regulation to adapt the immune system of animals residing
      in the tropical zone.

PMID- 20030541
TI  - Light at night alters the parameters of the eclosion rhythm in a tropical fruit
      fly, Drosophila jambulina.
AB  - We investigated the effects of natural light at night (LAN) in the field and
      artificial LAN in the laboratory on the circadian rhythm of pupal eclosion in a
      tropical wild type strain of Drosophila jambulina captured at Galle, Sri Lanka
      (6.1(o)N, 80.2(o)E). The influence of natural LAN, varying in intensity from
      0.004 lux (starlight intensity) to 0.45 lux (moonlight intensity), on the
      entrainment pattern of the circadian rhythm of eclosion at 25(o) +/- 0.5(o)C was
      examined by subjecting the mixed-aged pupae to natural cycles of light and
      darkness at the breeding site of this strain in the field. The eclosion peak was
      approximately 2 h prior to sunrise, and the 24 h rhythmicity was the most robust.
      Effects of artificial LAN at 25(o) +/- 0.5(o)C were determined in the laboratory
      by subjecting pupae to LD 12:12 cycles in which the light intensity of the
      photophase was 500 lux in all LD cycles, while that of the scotophase was either
      0 lux (complete darkness, DD), 0.5, 5, or 50 lux. In the 0 lux LAN condition
      (i.e., the control experiment), the eclosion peak was approximately 2 h after
      lights-on, and the 24 h eclosion rhythm was not as strong as in the 0.5 lux LAN
      condition. The entrainment pattern in 0.5 lux LAN was strikingly similar to that
      in the field, as the 0.5 lux LAN condition is comparable to the full moonlight
      intensity in the tropics. LAN at 0.5 lux dramatically altered both parameters of
      entrainment, as the eclosion peak was advanced by approximately 4 h and the 24 h
      eclosion rhythm was better than that of the control experiment. LAN at 5 lux,
      however, resulted in a weak eclosion rhythm that peaked in the subjective
      forenoon. Interestingly, the 50 lux LAN condition rendered the eclosion events
      unambiguously arrhythmic. After-effects of LAN on the period (tau) of the free
      running rhythm and the nature of eclosion rhythm were also determined in DD by a
      single LD 12:12 to DD transfer. After-effects of the LAN intensity were observed
      on both the tau and nature of the eclosion rhythm in all four experiments. Pupae
      raised in 0.5 lux LAN exhibited the shortest tau (20.6 +/- 0.2 h, N = 11 for this
      and subsequent values) and the most robust rhythm, while pupae raised in 50 lux
      LAN had the longest tau (29.5 +/- 0.2 h) and weakest rhythm in DD. Thus, these
      results demonstrate the intensity of LAN, varying from 0 to 50 lux, profoundly
      influences the parameters of entrainment as well as free-running rhythmicity of
      D. jambulina. Moreover, the observed arrhythmicity in LD 12:12 cycles caused by
      the 50 lux LAN condition appeared to be the masking effect of relatively bright
      light at night, as the LD 12:12 to DD transfer restored the rhythmicity, although
      it was rather weak.

PMID- 20030542
TI  - Plasma levels of interferon-gamma correlate with age-related disturbances of
      circadian rhythms and survival in a non-human primate.
AB  - Aging can be associated with changes in circadian rhythms and reduction in
      adaptive immune responses accompanied by expansion of memory T cells and elevated
      levels of pro-inflammatory cytokines. Recent findings suggest the cytokine
      interferon-gamma (IFN-gamma) can affect the function of the hypothalamic
      suprachiasmatic nucleus (SCN), the master mammalian circadian pacemaker, both in
      vitro and in vivo. We studied the correlation of plasma levels of IFN-gamma and
      changes in circadian rhythms in a non-human primate species, the nocturnal mouse
      lemur (Microcebus murinus). Plasma IFN-gamma and dehydroepiandrosterone sulfate
      (DHEA-S), a known biomarker of aging, were determined in middle- to old-age
      animals by immunoenzymoassay. Daily rhythms of locomotor activity and body
      temperature as well as survival time of the lemurs were recorded. With aging,
      mean levels of DHEA-S decreased whereas IFN-gamma increased. Aged animals showed
      biological rhythm alterations characterized by a high percentage of diurnal
      activity, anticipation of the activity onset relative to lights-off, short free
      running period, and delayed occurrence of minimal body temperature. The magnitude
      of these disturbances was correlated with the plasma level of IFN-gamma but not
      DHEA-S. Most remarkably, in contrast to DHEA-S, increased levels of IFN-gamma
      correlated with duration of the lifetime of the lemurs. These results show the
      degree of circadian rhythm alterations in an individual is correlated with plasma
      IFN-gamma level during aging, and that plasma IFN-gamma level may predict
      survival, at least in this non-human primate.

PMID- 20030543
TI  - Amber lenses to block blue light and improve sleep: a randomized trial.
AB  - All light is not equal: blue wavelengths are the most potent portion of the
      visible electromagnetic spectrum for circadian regulation. Therefore, blocking
      blue light could create a form of physiologic darkness. Because the timing and
      quantity of light and darkness both affect sleep, evening use of amber lenses to
      block blue light might affect sleep quality. Mood is also affected by light and
      sleep; therefore, mood might be affected by blue light blockade. In this study,
      20 adult volunteers were randomized to wear either blue-blocking (amber) or
      yellow-tinted (blocking ultraviolet only) safety glasses for 3 h prior to sleep.
      Participants completed sleep diaries during a one-week baseline assessment and
      two weeks' use of glasses. Outcome measures were subjective: change in overall
      sleep quality and positive/negative affect. Results demonstrated that sleep
      quality at study outset was poorer in the amber lens than the control group. Two-
      by three-way ANOVA revealed significant (p < .001) interaction between quality of
      sleep over the three weeks and experimental condition. At the end of the study,
      the amber lens group experienced significant (p < .001) improvement in sleep
      quality relative to the control group and positive affect (p = .005). Mood also
      improved significantly relative to controls. A replication with more detailed
      data on the subjects' circadian baseline and objective outcome measures is
      warranted.

PMID- 20030544
TI  - Circadian variability of bilirubin in healthy men during normal sleep and after
      an acute shift of sleep.
AB  - Bilirubin is a laboratory test widely used for patient care, especially neonatal
      patients and patients with anemia or suspected liver disorders. Bilirubin has
      also been shown to be associated with sleep pattern and oxidative stress. The aim
      of this study was to investigate the variation of bilirubin in a group of healthy
      individuals with normal night sleep as well as during acutely displaced sleep, as
      sleep timing varies immensely between individuals while clinical samples are
      still mainly taken in the morning. We studied the diurnal variation of bilirubin
      during night-sleep and day-sleep conditions in seven healthy volunteers. Serum
      samples were collected every hour (50 samples/individual) to evaluate the effect
      of different sampling times and sleep displacement on the test results. The mean
      acrophases (peak time) occurred at 10.6 h during the night-sleep condition and at
      18.4 h during the day-sleep condition. The diurnal intraindividual variation was
      high during both the night-sleep and day-sleep conditions, with coefficients of
      variation (CV) in the range of 12.8 to 42.5%. The diurnal variation was higher
      during the day compared to night-sleep condition. Thus, bilirubin sampling should
      be restricted to the morning, preferably after a normal night sleep, to minimize
      intraindividual variation.

PMID- 20030545
TI  - Time-of-day effects on fatigue during a sustained anaerobic test in well-trained
      cyclists.
AB  - The aim of this study was to evaluate time-of-day effects on fatigue during a
      sustained anaerobic cycling exercise. Sixteen healthy male competitive cyclists
      were asked to perform a 60 s Wingate test against a braking load of 0.087 kg.kg
      body mass(-1) during two experimental sessions, which were set up either at 06:00
      or 18:00 h in counterbalanced order. There was only one session per day with a
      recovery period of at least 36 h between the two sessions. Each subject was
      trained to perform the test. The body mass used to determine the braking load was
      that of the first test session for each subject and remained constant throughout
      the two test periods. During the test, peak power (PP), mean power during the
      first 30 s (MP30 s) and the full 60 s of the test (MP60 s), and fatigue (i.e.,
      the decrease in power output values throughout the exercise) were analyzed.
      Results confirmed the existence of diurnal variation in anaerobic power output.
      PP, MP30 s, and MP60 s were significantly higher at 18:00 than 06:00 h, with
      gains equal to 8.2, 7.8, and 7.8%, respectively. Moreover, all the power output
      values recorded in the evening were higher than those recorded in the morning,
      indicating that fatigue induced by this exercise is not affected by time-of-day
      in male competitive cyclists. It is hypothesized that the freedom and complexity
      of pedalling could allow adaptations in movement patterns, as a function of time
      of-day, in order to maintain higher performance in the evening. For practical
      considerations, the more complex the movements required to perform a sport, the
      more the time-of-day effect can be taken into account and adapted to by the
      trained athlete, particularly in cyclic sporting disciplines such as swimming,
      running, rowing, and kayaking.

PMID- 20030546
TI  - Effects of aerobic exercise on the circadian rhythm of heart rate and blood
      pressure.
AB  - Although the effects of aerobic exercise on resting heart rate, heart rate
      variability, and blood pressure have been investigated, there are scant data on
      the effects of aerobic exercise on the circadian rhythm of such cardiovascular
      parameters. In this study, we investigated the effects of aerobic exercise on the
      24 h rhythm of heart rate and ambulatory blood pressure in the morning, when
      cardiovascular events are more common. Thirty-five healthy young subjects were
      randomized to control and aerobic exercise groups. Subjects in the latter group
      participated in their respective exercise program for two months, while those in
      the former group did not exercise. Twenty-four-hour electrocardiogram and
      ambulatory blood pressure monitoring data were obtained at baseline and at the
      end of the exercise intervention. The control group showed no changes, while the
      aerobic exercise group showed a significant decrease in heart rate (73.7 +/- 6.6
      bpm to 69.5 +/- 5.1 bpm, p < 0.005) and sympathetic activity such as LF/HF ratio
      (2.0 +/- 0.7 to 1.8 +/- 0.6, p < 0.05) throughout the 24 h period, particularly
      in the daytime. The decrease in the heart rate was most prominent in the morning.
      However, heart rate and LF/HF ratio showed no statistical changes during the
      night. No significant changes were observed in blood pressure. These findings
      suggest aerobic exercise exerts beneficial effects on the circadian rhythm of
      heart rate, especially in the morning.

PMID- 20030547
TI  - Seasonality of pneumonia admissions and its association with climate: an eight
      year nationwide population-based study.
AB  - The aim of the study was to examine seasonal variability in monthly admissions
      for community-acquired pneumonia (CAP) in Taiwan. Our study sample comprised
      477,541 pneumonia patients in Taiwan between 1998 and 2005, inclusive. Results
      showed a fairly consistent seasonal pattern of pneumonia admissions, regardless
      of sex and age, and for the groups combined. Seasonal trends showed a peak in
      hospitalizations from January through April, followed by a sharp decrease in May
      and a trough from August through October. The auto-regressive integrated moving
      average (ARIMA) test found significant seasonality for all age and sex groups and
      for the whole sample (all p < 0.001). After adjusting for seasonality, month, and
      trends, the ARIMA regression models revealed that the monthly pneumonia
      admissions rate was significantly associated with ambient temperature, for the
      total sample, for female groups, and for the 65-74 and > or =75 age groups (all p
      < 0.01). A 1 degrees C decrease in ambient temperature was associated with
      roughly a 0.03 increase in monthly pneumonia admissions rate (per 10,000 people)
      for the entire sample. We conclude the monthly pneumonia admissions rate was
      significantly associated with seasonality, and was higher in periods with low
      ambient temperatures.

PMID- 20030548
TI  - Season of birth and smoking: findings from the Northern Finland 1966 Birth
      Cohort.
AB  - A season of birth effect in addictive disorders has scarcely been studied. As
      smoking is known to be a highly addictive behavior, we examined whether there
      exists an association between season of birth and smoking habits among the
      general population in the Northern Finland 1966 Birth Cohort (NFBC, n = 8,319).
      The birth month of each cohort member was categorized into one of the four
      seasons: spring (March-May), summer (June-August), autumn (September-November),
      or winter (December-February). Smoking habits of the cohort members were assessed
      by a postal questionnaire at the age of 31 yrs. Those who reported that they
      regularly smoked 11 or more cigarettes/day were regarded as heavy smokers. The
      association between season of birth and smoking was assessed with a logistic
      regression analysis: first, after controlling for early pregnancy-related and
      perinatal characteristics (Model 1) and second, after controlling for cohort
      members' hospital-treated psychiatric disorders, suicide attempts, adult
      educational level, and marital status (Model 2). Compared to males born in
      winter, the likelihood for heavy daily smoking was significantly increased, up to
      1.3-fold, among males born in the autumn in both logistic regression models.
      However, among females the likelihood for heavy smoking was statistically
      significantly elevated among those born during any season other than winter.
      Season of birth may modify the development of dopaminergic or other
      neurotransmitter systems divergently among males and females. Altered expression
      of dopaminergic genes due to environmental climatic factors could explain the
      association between season of birth and heavy smoking.

PMID- 20030549
TI  - Professor Tom Reilly (1941-2009).

PMID- 20030550
TI  - Inflexibility as an interactional phenomenon: Using conversation analysis to re
      examine a symptom of autism.
AB  - Many accounts of autism spectrum disorder (ASD) imply that the condition's
      behavioural 'symptoms' are direct reflexes of underlying deficits. In doing so,
      however, they invariably overlook the social contexts in which symptomatic
      behaviours occur and are identified as pathological. This study addresses this
      issue, using conversation analysis (CA) to examine the emergence of
      inflexibility, a behavioural trait symptomatic of ASD, during play involving an
      adult and diagnosed child. We argue that 'inflexibility' is the product of the
      child's strategic attempts to retain control over the unfolding interaction,
      within a context where such attempts breach normative expectations about adult
      child play. Furthermore, it demonstrates that the adult does not resist these
      attempts, on occasion even explicitly providing opportunity for subsequent
      inflexibility. This challenges the assumption that ASD's behavioural profile
      solely represents the endpoint of underlying deficit, and demonstrates how 'non
      impaired' speakers can be implicated in the manifestation of symptomatic
      behaviours.

PMID- 20030552
TI  - Speech after radial forearm free flap reconstruction of the tongue: a
      longitudinal acoustic study of vowel and diphthong sounds.
AB  - The purpose of this study was to use acoustic analyses to describe speech
      outcomes over the course of 1 year after radial forearm free flap (RFFF)
      reconstruction of the tongue. Eighteen Canadian English-speaking females and
      males with reconstruction for oral cancer had speech samples recorded (pre
      operative, and 1 month, 6 months, and 1 year post-operative). Acoustic
      characteristics of formants (F1, F2), fundamental frequency (F0), and duration of
      699 vowel and diphthong tokens were analysed. Furthermore, the changes in size of
      the vowel space area were studied, as well as the effects of radiation therapy
      (RT) and inclusion of the floor of the mouth (FOM) in the reconstruction. RFFF
      reconstruction was found to affect several characteristics in males, and a
      minimal number of variables in females. General signs of reduced ability to
      articulate were not observed. RT and FOM had no differing effects compared to non
      RT or non-FOM. There were individual differences between patients.

PMID- 20030551
TI  - The relationship between articulatory control and improved phonemic accuracy in
      childhood apraxia of speech: a longitudinal case study.
AB  - Jaw movement patterns were examined longitudinally in a 3-year-old male with
      childhood apraxia of speech (CAS) and compared with a typically developing
      control group. The child with CAS was followed for 8 months, until he began
      accurately and consistently producing the bilabial phonemes /p/, /b/, and /m/. A
      movement tracking system was used to study jaw duration, displacement, velocity,
      and stability. A transcription analysis determined the percentage of phoneme
      errors and consistency. Results showed phoneme-specific changes which included
      increases in jaw velocity and stability over time, as well as decreases in
      duration. Kinematic parameters became more similar to patterns seen in the
      controls during final sessions where tokens were produced most accurately and
      consistently. Closing velocity and stability, however, were the only measures to
      fall within a 95% confidence interval established for the controls across all
      three target phonemes. These findings suggest that motor processes may differ
      between children with CAS and their typically developing peers.

PMID- 20030553
TI  - Conversation after right hemisphere brain damage: motivations for applying
      conversation analysis.
AB  - Despite the well documented pragmatic deficits that can arise subsequent to Right
      Hemisphere Brain Damage (RHBD), few researchers have directly studied everyday
      conversations involving people with RHBD. In recent years, researchers have begun
      applying Conversation Analysis (CA) to the everyday talk of people with aphasia.
      This research programme has provided novel insights into the complex inter
      relationship between impairment, language use, and interactional organization.
      This paper will argue that the detailed, inductive approach of CA is well suited
      to investigating pragmatic communication disorders resulting from RHBD, and will
      help to elaborate previous findings about RHBD and conversation. In particular,
      this paper will review and discuss previous investigations of conversation after
      RHBD, and put forward arguments relating to how CA might be applied to talk-in
      interaction involving people with RHBD.

PMID- 20030554
TI  - Stuttering and lexical category in adult Arabic speakers.
AB  - The purpose of this study was to test whether the content and function word
      dichotomy of speech disfluency found in English-speaking adults who stutter (AWS)
      was evident in a language other than English. A group of adult Arabic-speaking
      AWS were sampled across spontaneous speaking, oral reading, and single-word
      naming tasks. Moments of disfluency were identified and examined in regard to
      lexical category. Results indicated no significant differences in the amount of
      disfluency occurring on content and function words. The production of combined
      content-function words, a unique feature of the Arabic language, was associated
      with a high level of disfluency. The linguistic bases of stuttering are discussed
      in regard to language-specific influences.

PMID- 20030555
TI  - Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus:
      implications for treatment strategies.
AB  - BACKGROUND. Given the apparent high mortality associated with the novel swine
      origin influenza A/H1N1 virus (S-OIV) in Mexico, we aimed to study the cytokine
      profiles induced by S-OIV and the effect of immunomodulators. METHODS. We assayed
      cytokines and their messenger RNA (mRNA) levels in culture supernatants of human
      macrophages infected with H5N1, S-OIV California/04/2009 (S-OIV-CA), S-OIV Hong
      Kong/415742 (S-OIV-HK), or seasonal H1N1 with or without celecoxib and
      mesalazine. RESULTS. Among the 12 cytokines showing detectable levels, levels of
      8 proinflammatory cytokines (interleukin [IL] 2R, IL-6, interferon [IFN] alpha,
      macrophage inflammatory protein [MIP] alpha, MIP-1beta, IFN-induced protein 10,
      regulated on activation, normal T cell expressed and secreted [RANTES], and
      monocyte chemotactic protein [MCP] 1) were higher in cells infected by H5N1 but
      similar among cells infected with H1N1, S-OIV-CA, or S-OIV-HK. The levels of the
      other 4 cytokines were similar for H5N1, H1N1, S-OIV-CA and S-OIV-HK. Among the 8
      cytokines induced by H5N1, 6 were suppressed by celecoxib and mesalazine. The
      mRNA levels of tumor necrosis factor alpha, IFN-gamma, IL-6, and MCP-1 induced by
      H5N1 were higher than the levels of other cytokines at 12 and/or 24 h.
      CONCLUSIONS. No major cytokine storm, as seen in H5N1 infection, is associated
      with S-OIV infection of cell lines. The mainstay of treatment for uncomplicated S
      OIV infections should be antiviral agents without immunomodulators. For
      individual S-OIV-infected patients with severe primary viral pneumonia, severe
      sepsis, and multiorgan failure, immunomodulators may be considered as an
      adjunctive therapy in clinical trials.

PMID- 20030556
TI  - CD4(+)CD25(+/hi)CD127(lo) phenotype does not accurately identify regulatory T
      cells in all populations of HIV-infected persons.
AB  - The most commonly used regulatory T cell (Treg) phenotypes,
      CD4(+)CD25(hi)CD127(lo) and CD4(+)CD25(hi)FoxP3(+), were simultaneously used to
      determine the Treg frequency in 2 different groups of human immunodeficiency
      virus (HIV)-infected persons, one viremic and other aviremic. As expected, a
      strong correlation between both Treg phenotypes was observed in the aviremic
      group (r = 0.913; P < .001), but surprisingly, this correlation was completely
      absent in the viremic group (r = 0.143; P = .572). Data on T cell activation
      levels of both HIV groups suggest that the CD4(+)CD25(hi)CD127(lo) phenotype
      could just be mirroring the elevated numbers of activated non-regulatory T cells
      in the viremic HIV group.

PMID- 20030557
TI  - Gene transfer vectors targeted to human prostate cancer: do we need better
      preclinical testing systems?
AB  - Destruction of cancer cells by genetically modified viral and nonviral vectors
      has been the aim of many research programs. The ability to target cytotoxic gene
      therapies to the cells of interest is an essential prerequisite, and the
      treatment has always had the potential to provide better and more long-lasting
      therapy than existing chemotherapies. However, the potency of these infectious
      agents requires effective testing systems, in which hypotheses can be explored
      both in vitro and in vivo before the establishment of clinical trials in humans.
      The real prospect of off-target effects should be eliminated in the preclinical
      stage, if current prejudices against such therapies are to be overcome. In this
      review we have set out, using adenoviral vectors as a commonly used example, to
      discuss some of the key parameters required to develop more effective testing,
      and to critically assess the current cellular models for the development and
      testing of prostate cancer biotherapy. Only by developing models that more
      closely mirror human tissues will we be able to translate literature publications
      into clinical trials and hence into acceptable alternative treatments for the
      most commonly diagnosed cancer in humans.

PMID- 20030558
TI  - A systematic review of intensive cardiopulmonary management after spinal cord
      injury.
AB  - Intensive cardiopulmonary management is frequently undertaken in patients with
      spinal cord injury (SCI), particularly due to the occurrence of neurogenic shock
      and ventilatory insufficiency and in an attempt to reduce secondary injury. We
      undertook a systematic review of the literature to examine the evidence that
      intensive care management improves outcome after SCI and to attempt to define key
      parameters for cardiopulmonary support/resuscitation. We review the literature in
      five areas: management of SCI patients in specialized centers, risk in SCI
      patients of cardiopulmonary complications, parameters for blood pressure and
      oxygenation/ventilation support following SCI, risk factors for cardiopulmonary
      insufficiency requiring ICU care after SCI, and preventative strategies to reduce
      the risks of cardiopulmonary complications in SCI patients. The literature
      supports that, in light of the significant incidence of cardiorespiratory
      complications, SCI patients should be managed in a monitored special care unit.
      There is weak evidence supporting the maintenance of MAP >85 mmHg for a period
      extending up to 1 week following SCI.

PMID- 20030559
TI  - Assessment of impairment in patients with acute traumatic spinal cord injury: a
      systematic review of the literature.
AB  - The most common primary end-point of the trial on treatment of traumatic spinal
      cord injury (SCI) is the degree of impairment. The American Spinal Injury
      Association (ASIA) Standards have been widely used to assess motor function and
      pin-prick and light-touch sensory function. In addition, pain assessment is
      another clinically relevant aspect of the impairment in individuals with SCI.
      Given this, we sought to systematically review the studies that focused on the
      psychometric properties of ASIA Standards and all previously used outcome
      measures of pain in the SCI population in the acute care setting. For the primary
      literature search strategy, the MEDLINE, CINAHL, EMBASE, and Cochrane databases
      were sought out. Subsequently, a secondary search strategy was carried out using
      the articles listed in the references of meta-analysis, systematic, and non
      systematic review articles. Two reviewers (JCF and VN) independently selected the
      articles that fulfill the inclusion and exclusion, assessed the level of evidence
      of each article, and appraised the psychometric properties of each instrument.
      Divergences during those steps were solved by consensus between both reviewers.
      Of 400 abstracts captured in our primary search strategy on the ASIA Standards,
      16 full articles fulfilled the inclusion and exclusion criteria. An additional 40
      references were obtained from two prior systematic reviews on ASIA Standards.
      While 45 of 56 of the studies on ASIA Standards provided level 4 evidence, there
      were 11 level 2b evidence studies. Convergent construct validity (n = 34),
      reliability (n = 12), and responsiveness (n = 10) were the most commonly studied
      psychometric properties of the ASIA Standards, but two prior studies examined
      their content validity. Of the 267 abstracts yielded in our primary search on
      pain assessment, 24 articles with level 4 evidence fulfilled the inclusion and
      exclusion criteria. There was no study that examined pain assessment in the acute
      care setting. While 18 of 24 articles studied an instrument for assessment of
      pain intensity, the remaining six studies were focused on classifications of pain
      in the SCI population. In conclusion, the ASIA Standards represent an appropriate
      instrument to categorize and evaluate spinal cord injured adults over time with
      respect to their motor and sensory function. Nevertheless, further investigation
      of the psychometric properties of the ASIA Standards is recommended due to a lack
      of studies focused on some key elements of responsiveness, including minimal
      clinically important difference. The visual analog scale (VAS) is the most
      commonly studied instrument of assessment of pain intensity in the SCI
      population. However, further investigation is required with regard to its
      reliability and responsiveness in the SCI population. Our results also suggest
      that there is no instrument with appropriate psychometric properties for this
      particular population.

PMID- 20030561
TI  - Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients
      have diminished stem cell capacity.
AB  - Human bone marrow stromal cells (BM-SCs) possess the potential to differentiate,
      self-renew, and produce diverse trophic/growth factors and are an excellent cell
      therapy tool for degenerative diseases. However, they exhibit different
      therapeutic efficacies, depending on the health status and age of the cell donor.
      Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by progressive motor neuron death in the central nervous system. In
      this study, we isolated BM-SCs from 11 ALS patients and characterized their
      potential secretory capacity of neurotrophic factors. We identified significant
      reductions in the expression of Oct-4 and Nanog , and in the trophic factors ANG,
      FGF -2, HGF, IGF-1, PIGF, SDF-1alpha , TGF-beta, and VEGF, but not in BDNF or
      ECGF. Migration of ALS-SCs was reduced, although the cells expressed the same
      markers for human mesenchymal phenotypes. These data suggest that ALS-SCs have
      diminished capacity as trophic mediators and may have reduced beneficial effects
      in cell therapy.

PMID- 20030560
TI  - Long-term gliosis and molecular changes in the cervical spinal cord of the rhesus
      monkey after traumatic brain injury.
AB  - Recovery of fine motor skills after traumatic brain injury (TBI) is variable,
      with some patients showing progressive improvements over time while others show
      poor recovery. We therefore studied possible cellular mechanisms accompanying the
      recovery process in a non-human primate model system, in which the lateral
      frontal motor cortex areas controlling the preferred upper limb were unilaterally
      lesioned, and the animals eventually regained fine hand motor function.
      Immunohistochemical staining of the cervical spinal cord, the site of
      compensatory sprouting and degeneration of corticospinal axons, showed profound
      increases in immunoreactivities for major histocompatibility complex class II
      molecule (MHC-II) and extracellular signal-regulated kinases (ERK1/2) up to 12
      months post lesion, particularly within the lateral corticospinal tract (LCST).
      Double immunostaining demonstrated that phosphorylated ERK1/2 colocalized within
      the MCH-II + microglia, suggesting a trophic role of long-term microglia
      activation after TBI at the site of compensatory sprouting. Active sprouting was
      observed in the LCST as well as in the spinal gray matter of the lesioned
      animals, as illustrated by increases in growth associated protein 43.
      Upregulation of Nogo receptor and glutamate transporter expression was also
      observed in this region after TBI, suggesting possible mechanisms for controlling
      aberrant sprouting and/or synaptic formation en route and interstitial glutamate
      concentration changes at the site of axon degeneration, respectively. Taken
      together, these changes in the non-human primate spinal cord support a long-term
      trophic/tropic role for reactive microglia, in particular, during functional and
      structural recovery after TBI.

PMID- 20030563
TI  - Plant strategies in relation to resource supply in mesic to wet environments:
      does theory mirror nature?
AB  - In ecology, strategy schemes based on propositions about the selection of plant
      attributes are common, but quantification of such schemes in relation to nutrient
      and water supply is lacking. Through structural equation modeling, we tested
      whether plant strategies related to nutrient and water/oxygen supply are
      reflected in a coordination of traits in natural communities. Structural equation
      models, based on accepted ecological concepts, were tested with measured plant
      traits of 105 different species across 50 sites in mesic to wet plant communities
      in the Netherlands. For each site, nutrient and water supply were measured and
      modeled. Hypothesized multivariate strategy models only partly reflected current
      theoretical schemes. Alternative models were consistent, showing that lack of
      consistency of the original models was because of (i) strong correlations among
      traits that supposedly belong to different strategy components; (ii) poor
      understanding of mechanisms determining the covariation of plant maximum height,
      leaf size, and stem density; and (iii) lack of integrative and long-term measures
      of nutrient supply needed to predict coordinated plant trait responses. Our main
      conclusion is that a combination of trade-offs (partly) across different plant
      organs and diverging effects of resource supply ultimately determines the
      coordination of plant traits needed to "make a living."

PMID- 20030562
TI  - Human-induced pluripotent stem cells produced under xeno-free conditions.
AB  - Induced pluripotent stem cells (iPSCs) have radically advanced the field of
      regenerative medicine by making possible the production of patient-specific
      pluripotent stem cells from adult individuals. While cell differentiation
      protocols have been successfully developed, and animal models of human disease
      have proved that these cells have the potential to treat human diseases and
      conditions produced as a consequence of aging, degeneration, injury, and birth
      defects, logistical issues still remain unsolved and hamper the possibility of
      testing these cells in human clinical trials. Among them is the widely spread use
      of animal products for the generation and culture of iPSCs. We report here a xeno
      free iPSC generation system that addresses all the steps of iPSCs production
      including the isolation and culture of adult skin fibroblasts, and iPSCs
      generation, expansion, and maintenance. iPSCs generated with a polycistronic
      lentiviral vector under xeno-free conditions displayed markers of pluripotency
      and gave rise to embryoid bodies (EBs) displaying indicators of the 3 primary
      germ layers. Xeno-free iPSCs injected into nude mice produced classic teratomas,
      and teratoma explants cultured under conditions favoring fibroblastic cells gave
      rise to cells morphologically indistinguishable from input cells. Protocols here
      described will facilitate the implementation of new cellular therapies for
      preclinical and clinical studies, potentially reducing the regulatory burden
      without compromising the differentiation potential of the cells.

PMID- 20030564
TI  - Increasing resistance of acinetobacter species to imipenem in United States
      hospitals, 1999-2006.

PMID- 20030565
TI  - In situ detection of inflammatory mediators in post mortem human brain tissue
      after traumatic injury.
AB  - Little is known about the molecular events following severe traumatic brain
      injury (TBI) in humans and to date there are no efficient therapies for the
      treatment of patients. In this study, the first of its kind in human tissue, a
      total of 21 post mortem trauma brain samples were analyzed. The inflammatory
      response within the brain tissue was explored by measuring the expression of
      various inflammatory cytokines at the mRNA and protein levels. These mediators
      were interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor
      (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony
      stimulating factor (GM-CSF). This study shows for the first time in human brain
      tissue that 1) pro-inflammatory mediator protein levels are significantly
      increased in situ following acute brain injury while anti-inflammatory cytokines
      protein levels remain unchanged; 2) the cerebral inflammatory response begins
      within minutes of acute TBI, much earlier than previously thought; 3) IL-6, IL-8,
      TNF-alpha, and IL-1beta mRNA levels are significantly increased following injury;
      4) the rise in cytokine protein level coincides with increased levels of their
      mRNAs suggesting that traumatic injury elicits an immediate cerebral inflammatory
      response. Altogether these data confirm and extend previous observations on the
      release of cytokines in the cerebrospinal fluid of severe TBI patients. Finally,
      this study highlights the need to characterize the cell source of cytokines and
      elucidate their mode of action.

PMID- 20030566
TI  - Differences in pharmacology and their translation into differences in clinical
      efficacy--a comparison of the renin angiotensin blocking agents irbesartan and
      losartan.
AB  - IMPORTANCE OF THE FIELD: Guidelines recommend five antihypertensive drug classes,
      but which particular drug to choose is up to the treating physician. We aimed at
      an in-depth comparison of two frequently used angiotensin receptor blockers to
      provide evidence for this decision. AREAS COVERED IN THIS REVIEW: Pharmacology of
      irbesartan and losartan, their blood-pressure-lowering efficacy, their
      tolerability/safety, end-organ protective effects and economic evaluation. WHAT
      THE READER WILL GAIN: Both drugs differ in their oral bioavailability, potential
      for food interactions, degree of metabolism, dosing interval, time to peak,
      volume of distribution and terminal half-life. Irbesartan provides a greater and
      longer-lasting antihypertensive effect and was determined to be cost effective
      over losartan in Denmark and Sweden. Irbesartan was more effective in preventing
      deterioration of kidney function in patients with diabetic nephropathy, being
      cost effective from a German perspective. There is only one end point trial for
      either drug in patients with left ventricular hypertrophy, heart failure and
      atrial fibrillation, but no direct comparison. TAKE HOME MESSAGE: There is an
      incremental clinical benefit of irbesartan over losartan in the treatment of
      hypertension and diabetic nephropathy which can be substantiated by corresponding
      preclinical study evidence. This has translated into an economic benefit in a
      number of country-specific evaluations.

PMID- 20030567
TI  - Bromocriptine--unique formulation of a dopamine agonist for the treatment of type
      2 diabetes.
AB  - IMPORTANCE TO THE FIELD: There is a large unmet need for new therapies to treat
      type 2 diabetes (T2DM) which reduce fasting and postprandial glucose without
      increasing insulin levels and which are not associated with weight gain or
      hypoglycemia. The quick-release formulation of bromocriptine (bromocriptine-QR;
      Cycloset) represents such a therapy. AREAS COVERED IN THE REVIEW: Bromocriptine
      QR's proposed mechanism of action, unique formulation and clinical efficacy and
      safety will be discussed. A Medline search was conducted using the terms:
      bromocriptine quick-release, circadian rhythms, treatment type 2 diabetes,
      insulin resistance, beta-cell dysfunction (years 1985 - 2009). WHAT THE READER
      WILL GAIN: The reader will gain an understanding of the importance of the brain
      as a target for the treatment of type 2 diabetes. In addition the safety,
      efficacy and indication for use of a first-in-class dopamine agonist as a
      treatment option for type 2 diabetes are discussed. TAKE HOME MESSAGE:
      Bromocriptine-QR is indicated to be used alone or in conjunction with all
      available treatments for type 2 diabetes. Although the mechanism of action is not
      fully understood, bromocriptine-QR's action points to a central target in the
      brain (hypothalamus) which may explain the observed peripheral improvements in
      metabolic parameters.

PMID- 20030568
TI  - Combined oral prolonged-release oxycodone and naloxone in opioid-induced bowel
      dysfunction: review of efficacy and safety data in the treatment of patients
      experiencing chronic pain.
AB  - IMPORTANCE OF THE FIELD: Despite proven analgesic efficacy, opioid use is
      associated with frequently dose-limiting bowel dysfunction that seriously impacts
      patients' quality of life (QoL). Agents used at present to manage opioid-induced
      constipation do not address the underlying opioid receptor-mediated cause of
      bowel dysfunction and are often ineffective. There is, therefore, a significant
      need for more effective treatment options. The combination of the strong opioid
      oxycodone and the opioid antagonist naloxone has the potential to prevent opioid
      induced bowel dysfunction (OIBD) while maintaining analgesic efficacy. OBJECTIVE:
      To review the safety and efficacy of oral prolonged-release (PR)
      oxycodone/naloxone in the treatment of patients experiencing chronic pain. AREAS
      COVERED IN THIS REVIEW: A MEDLINE search was done (January 2002 - July 2009) for
      available literature for prolonged release oxycodone and naloxone in different
      patient groups. Results were limited to English-language and clinical trials.
      Data were also obtained from congress materials. WHAT KNOWLEDGE THE READER WILL
      GAIN: Unmet needs of opioid pain treatment in terms of OIBD, reduced QoL and low
      treatment compliance, leading to reduced efficacy. A data overview demonstrates
      the efficacy and tolerability of PR oxycodone/naloxone in the management of
      severe chronic pain without the burden of severe gastrointestinal adverse events.
      The combined formulation of a highly effective opioid and an antagonist that acts
      locally to reduce gastrointestinal side effects is expected to simplify pain
      management. TAKE HOME MESSAGE: The combination of PR oxycodone/naloxone offers
      the potential of maintaining normal bowel function in patients requiring opioid
      therapy--it is a strong analgesic that is well tolerated.

PMID- 20030569
TI  - Health-related quality of life and depression in dialysis patients: associations
      with current smoking.
AB  - OBJECTIVE: The study explored health-related quality of life (HRQoL) and
      depression in a culturally homogeneous dialysis patient population. Furthermore,
      the associations between HRQoL and depression with current smoking were
      elaborated. MATERIAL AND METHODS: In a cross-sectional study of 301 dialysis
      patients from 10 dialysis centres in Norway, HRQoL was evaluated with the Kidney
      Disease and Quality of Life Short Form, version 1.3. Physical component summary
      scores (PCS) and mental component summary scores (MCS) were computed. Depression
      was assessed using the Beck Depression Inventory (BDI), and Cognitive Depression
      Index (CDI) was calculated. Depression was defined as a BDI score greater than
      14. RESULTS: HRQoL was poorer in dialysis patients compared with population
      norms. Depression was prevalent (33.2%), and differed significantly between
      smokers and non-smokers (52.8 vs 26.4%, p < 0.001). MCS was significantly reduced
      in smokers compared with non-smokers (44.1 +/- 12.2 vs 48.7 +/- 10.3, p < 0.001),
      but there was no difference in PCS (35.7 +/- 10.2 vs 37.1 +/- 10.4, not
      significant). Current smoking was independently associated with higher BDI score
      (p = 0.039), as well as with higher CDI score (p = 0.005) and worse score on MCS
      (p = 0.002), after adjustments for multiple covariates. CONCLUSIONS: HRQoL is
      lower in Norwegian dialysis patients than in the general population, and
      depression is prevalent. The study suggests that poor perceived mental aspects of
      HRQoL and depression are associated with current smoking in dialysis patients,
      but a causal relationship remains to be shown.

PMID- 20030570
TI  - Body size and obesity patterns in Caboclo populations from Para, Amazonia,
      Brazil.
AB  - BACKGROUND: In many developing countries overweight, obesity and obesity-related
      morbidity are becoming a problem of increasing public health importance. The
      purpose of this study was to investigate differences in body size and body
      composition with age in adults of the Caboclo populations from the Brazilian
      Amazon as well as to examine the prevalence of overweight and obesity in adults
      aged 20-75 years, taking into account recent trends for the whole country.
      Caboclo are genetically and culturally admixed rural peasant groups that live
      along the Amazon River and its tributaries in Brazil, and there are few previous
      studies of their health and lifestyle. SUBJECTS AND METHODS: A total of 304
      subjects (149 males and 155 females) from two socioecologically different areas
      were studied. Height, weight and skinfolds (tricipital, subscapular and
      suprailiac) were measured; international intervals (WHO) for overweight and
      obesity were used. RESULTS: Women showed significantly lower values than men for
      height, weight, upper arm circumference and fat-free mass and higher values for
      triceps, subscapular and suprailiac skinfolds and body fat (%). In the overall
      sample combined overweight and obesity was 47.8% in men and 50.8% in women. When
      compared to recent values published for the Northern region and for the whole of
      Brazil, 20.5% of Caboclo women aged 20-75 years were obese, which is higher than
      all other populations, including other rural samples. Caboclo men showed the
      highest rates of obesity (9.1%) and overweight (39.1%) of any rural population
      from the country, including Northern Brazil. CONCLUSION: The results suggest an
      effect of increased Western lifestyle influence on the body composition of these
      Caboclo populations. Considering that these are rural populations with limited
      access to education and health care, the high prevalence of overweight and
      obesity associated with low socio-economic status makes them a vulnerable group
      that deserves a higher level of attention by the country's public health
      authorities.

PMID- 20030571
TI  - Ischemic colitis in the elderly: predictors of the disease and prognostic factors
      to negative outcome.
AB  - OBJECTIVE: Ischemic colitis (IC) poses a challenge for physicians, especially in
      elderly patients. The aim of this study was to identify predictors of the disease
      and to assess the factors predicting its evolution in elderly people. MATERIAL
      AND METHODS: A retrospective study was undertaken in patients with IC admitted to
      Padua General Hospital between 2003 and 2008. Only patients with biopsy-proven IC
      were considered. Fifty control subjects were randomly selected from those seen at
      our units for acute geriatric disease during the same interval. Patients with IC
      were classified as having either a positive or negative outcome. RESULTS: A total
      of 46 patients were considered. The risk factors for IC identified from
      univariate analysis were analyzed in a multivariate logistic regression model and
      constipation [adjusted odds ratio (OR) 4.8; 95% confidence interval (CI) 1.1
      20.1], vasculopathy (OR 4.9; 95% CI 1.4-16.6), hepatitis C virus (HCV) (OR 9.9;
      95% CI 1.1-92.9) and cancer (OR 7.5; 95% CI 2.1-26.9) confirmed their independent
      significance as risk factors. Hematochezia was predictive of a positive outcome
      (OR 0.07; 95% CI 0.02-0.40), while cancer (OR 3.2; 95% CI 1.2-11.9), HCV
      positivity (OR 9.6; 95% CI 1.6-56.5), signs of peritonism (OR 4.7; 95% CI 1.2
      18.4), localization in the right colon (OR 5.75; 95% CI 1.5-21.9) and increased
      levels of lactate dehydrogenase (LDH) and urea were independently predictive of a
      negative outcome. CONCLUSIONS: Elderly patients with IC are characterized by
      significant comorbidities. The absence of hematochezia and the presence of a
      concomitant malignancy, HCV, a marked increase in urea and LDH and disease
      involving only the right colon are factors that may predict a negative outcome in
      elderly patients.

PMID- 20030573
TI  - Atrial fibrillation after thoracic surgery for lung cancer: use of a single cut
      off value of N-terminal pro-B type natriuretic peptide to identify patients at
      risk.
AB  - Postoperative atrial fibrillation (AF) is a well-known complication occurring
      after thoracic surgery. B-type natriuretic peptide has recently been investigated
      as a predictive marker of postoperative AF after cardiac surgery. The aim of this
      study was to evaluate a definite cut-off for N-terminal pro-B type natriuretic
      peptide (NT-proBNP) in predicting postoperative AF in lung cancer patients. NT
      proBNP was determined before and after surgery in 400 patients. Cardiac function
      was monitored by continuous postoperative ECG and clinical cardiological
      evaluation. AF occurred in 18% of the patients. Receiver operating characteristic
      curve analyses identified a cut-off of 182.3 ng l(-1) as the one with the highest
      sensitivity and specificity. Perioperative increased levels of NT-proBNP seem to
      predict postoperative AF in patients undergoing thoracic surgery, and a single
      cut-off of 182.3 ng l(-1) can be used to select high-risk patients who could
      receive preventive therapy, leading to a considerable decrease in the total costs
      associated with the management of this complication.

PMID- 20030572
TI  - Anti-mutagenic lichen extract has double-edged effect on azoxymethane-induced
      colorectal oncogenesis in C57BL/6J mice.
AB  - This study compared the effects of three anti-mutagenic lichen extracts on
      colorectal oncogenesis in azoxymethane (AOM)-treated mice and determined whether
      the extracts also regulated the homeostatic response to genotoxic damage.
      C57BL/6J mice (n = 12 per group) were treated with the lichen extracts
      Antimutagen-He (AMH): AMH-C, AMH-D, or AMH-E dimethyl sulfoxide (DMSO, control)
      for 2 weeks. At the end of the treatment, mice were given a single AOM injection
      to induce DNA damage and killed 6 h later for measuring apoptosis and
      proliferation. Apoptotic and proliferation indexes in mice treated with AMH-C,
      AMH-D, and AMH-E were 0.61%, 1.41%, and 0.77%; and 30.62%, 21.93%, and 27.27%,
      respectively, which were significantly lower than those of control mice (5.88%
      and 38.69%) (p < 0.05). To examine the effects of lichen extracts on colorectal
      cancer, separate groups of mice (n = 25 per group) treated with AMH-C, AMH-D, AMH
      E, or DMSO were given 4-weekly AOM injections to induce oncogenesis. Mice were
      killed 24 weeks after the last AOM injection for assessing colon tumor formation.
      Colonic tumor incidences were 47.3%, 13%, and 20%; the tumor volumes were 18.47,
      2.75, and 10.78 mm(3), respectively, in mice treated with AMH-C (p < 0.05), AMH-D
      (p < 0.05), and AMH-E (p > 0.05), compared to 24% and 13.28 mm(3) in mice of
      control correspondingly. No lichen extract showed evident toxic effects on mice.
      No usnic acid was found in these lichen extracts. The regulation of acute
      apoptosis and cell proliferation in colonic epithelial cells and the anti
      mutagenesis do not seem directly related to the cancer protective effect.

PMID- 20030574
TI  - Exploring QSAR for CYP11B2 binding affinity and CYP11B2/CYP11B1 selectivity of
      diverse functional compounds using GFA and G/PLS techniques.
AB  - A data set of a series of 132 structurally diverse compounds with cytochrome 11B2
      and 11B1 (CYP11B2 and CYP11B1) enzyme inhibitory activities was subjected to
      molecular shape analysis to explore contributions of shape features as well as
      electronic, structural, and physicochemical parameters toward enzyme inhibitory
      activities, in search of appropriate molecular scaffolds with optimum
      substitutions for highly potent CYP11B2 inhibitors. Genetic function
      approximation (GFA) and genetic partial least squares (G/PLS) were used as
      chemometric tools for modeling, and the derived equations were of acceptable
      statistical quality considering both internal and external validation parameters
      (Q(2): 0.514-0.659, R(2)(pred): 0.510-0.734). The G/PLS models with spline option
      for CYP11B2 and CYP11B1 inhibition and selectivity modeling appeared to be the
      best models based on r(m)(2)((overall)) criterion. The study indicates the
      importance of the pyridinylnaphthalene and pyridylmethylene-indane scaffolds with
      less polar and electrophilic substituents for optimum CYP11B2 inhibitory activity
      and CYP11B2/CYP11B1 selectivity.

PMID- 20030576
TI  - Helicobacter pylori, nutrition and smoking interactions: their impact in gastric
      carcinogenesis.
AB  - Gastric cancer (GC) is the result of a long multi-step and multifactorial process
      involving possible interactions between Helicobacter pylori infection,
      environmental exposures and host genetic susceptibility. Interactions between H.
      pylori infection, tobacco smoking and dietary antioxidants are biologically
      plausible. Positive interactions between risk factors imply that, in certain
      subgroups of the population, the risk of GC associated with simultaneous exposure
      to these factors is higher than that in the rest of the population, and these
      subgroups have to be the target for preventive measures. Using PubMed, we
      reviewed all studies published in English up to December 2008 carried out in
      humans on interactions between H. pylori infection and smoking exposure and
      between H. pylori infection and dietary factors in gastric carcinogenesis.
      Although relatively few epidemiological studies have evaluated the effect of the
      interaction between smoking and H. pylori infection on GC risk, there is a
      suggestion of a positive interaction between the two factors. In contrast,
      evidence suggests a negative interaction between dietary antioxidants and H.
      pylori infections on GC risk. The potential protective effect of dietary
      antioxidants such as vitamins C and E and beta-carotene seems to be stronger in
      those infected by H. pylori, even though results are inconsistent. In Asian
      populations, subjects infected by H. pylori and with high dietary salt intake may
      have a higher risk of GC than subjects without H. pylori infection and with a low
      salt intake. The risk of GC associated with red meat, processed meat or
      endogenous formation of nitrosamines appears to only be observed in subjects
      infected by H. pylori. More and larger epidemiological studies, mainly
      prospective studies, are necessary to reach a more definitive conclusion on these
      interactions.

PMID- 20030577
TI  - Non-invasive evaluation of the fibrosis stage in chronic hepatitis C: a
      comparative analysis of nine scoring methods.
AB  - OBJECTIVE: Liver biopsy is an invasive procedure and new surrogate markers to
      assess fibrosis are needed. We performed a comparative external evaluation of
      nine non-invasive scores of liver fibrosis and tried to identify other potential
      biochemical markers of low-stage liver fibrosis in chronic hepatitis C (CHC).
      MATERIAL AND METHODS: We included 429 previously untreated consecutive patients
      from a single centre who underwent a liver biopsy between January 1999 and April
      2009. Biopsies were evaluated for the stage of fibrosis according to the METAVIR
      scoring method. RESULTS: None of the evaluated scores were adequate to disclose
      null-low fibrosis due to a lack of specificity at the proposed cut-offs and the
      poor sensitivity of lower cut-offs. Serum ferritin and cholesterol values were
      found to be independently related to the fibrosis stage and their inclusion in
      the best performing scores at lower cut-off values (the APRI and King's scores)
      improved the sensitivity for null-low fibrosis by 8% with a specificity >or= 93%.
      CONCLUSIONS: Approximately 30% of patients with null-low fibrosis may be
      accurately identified by supplementing current scores with new independent
      variables (serum ferritin and cholesterol), thus obviating the need for a liver
      biopsy.

PMID- 20030578
TI  - Liver transplantation of patients with cryptogenic cirrhosis: clinical
      characteristics and outcome.
AB  - OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH)
      and unapparent alcohol abuse may be underlying causes of cryptogenic cirrhosis,
      but the frequencies of these underlying factors differ between studies. Also,
      previous studies have shown various outcomes after orthotopic liver
      transplantation (OLT) for cryptogenic cirrhosis. The aims of this study were (1)
      to evaluate the presence of NAFLD in patients with cryptogenic cirrhosis
      evaluated for OLT and (2) to compare the severity of liver disease and patient
      survival in OLT candidates with cryptogenic cirrhosis and those with cirrhosis of
      another known origin. MATERIAL AND METHODS: Four-hundred and seventy adult
      patients with end-stage liver cirrhosis evaluated for OLT between 1990 and 2004
      were included, of whom 39 had cryptogenic cirrhosis. Clinical, histological and
      laboratory data that had been prospectively collected were re-evaluated. RESULTS:
      Seventeen (44%) of the cryptogenic patients had NAFLD in a previous liver biopsy
      and/or clinical features of the metabolic syndrome. Two patients had occult
      alcohol over-consumption and one patient had burnt-out AIH. Cryptogenic patients
      had significantly higher frequencies of diabetes, ascites, and hyponatraemia and
      weight loss. Patient survival was similar between cryptogenic patients and
      cirrhotics with a known aetiology. CONCLUSIONS: Re-evaluation of patient data
      discovered probable underlying aetiologies in 51% of patients with cryptogenic
      cirrhosis evaluated for OLT, of which NAFLD was the most common (44%). Although
      cryptogenic patients had a more advanced liver disease when evaluated for OLT,
      patient survival was similar. Recent weight loss was significantly more common in
      cryptogenic patients, possibly being a sign of liver decompensation and
      signalling a need for OLT evaluation.

PMID- 20030579
TI  - Bile duct stone procedures are more frequent in patients with hypothyroidism. A
      large, registry-based, cohort study in Finland.
AB  - OBJECTIVE: Delayed bile flow may induce the formation/accumulation of common bile
      duct stones (CBDS). Bile flow is delayed in hypothyroidism, partly due to
      insufficient sphincter of Oddi relaxation. Patients with CBDS have higher
      incidences of clinical and subclinical hypothyroidism compared to healthy
      controls and gallbladder stone patients. The aim of this large registry-based
      study was to investigate the prevalence of CBDS in patients with diagnosed
      hypothyroidism compared to age-, sex- and living area-adjusted glaucoma (control)
      patients. MATERIAL AND METHODS: Between 1987 and 2001, all patients with approved
      Special Medical Coverage (SMC) for hypothyroidism or glaucoma, and without other
      SMC approvals, were included. The glaucoma (control) cohort was adjusted for age,
      sex and area of residence. For each patient, onset of SMC, all prescription drugs
      and treatments for CBDS were noted. RESULTS: A total of 14,334 patients in each
      group met the inclusion criteria. Thirty-three patients (0.23%) in the
      hypothyroidism cohort and 23 (0.16%) in the glaucoma cohort had been treated for
      CBDS (p = 0.018). The groups did not differ in the number of CBDS treatments
      before the diagnosis of hypothyroidism or glaucoma. However, after the diagnosis
      of hypothyroidism or glaucoma there were significantly more CBD stone patients in
      the hypothyroid cohort (n = 25) than in the glaucoma cohort (n = 14) (p < 0.05).
      CONCLUSIONS: Diagnosed hypothyroidism is a significant risk factor for CBDS. We
      hypothesize that CBD stone formation begins during the untreated period and
      develops/matures even after the medication has been initiated, raising the
      question of the efficiency of treatment in this respect. When treating CBDS
      patients, one should be aware of the possible hypothyroid background.

PMID- 20030580
TI  - Extended lamivudine consolidation therapy in hepatitis B e antigen-positive
      chronic hepatitis B patients improves sustained hepatitis B e antigen
      seroconversion.
AB  - OBJECTIVES: Longer lamivudine (LAM) consolidation therapy after hepatitis B e
      antigen (HBeAg) seroconversion has been demonstrated to reduce the cumulative
      relapse rate. However, the optimal interval of LAM consolidation therapy remains
      controversial. We evaluated the post-treatment durability of LAM-induced HBeAg
      seroconversion and the length of LAM consolidation therapy required to maintain
      sustained HBeAg seroconversion. MATERIAL AND METHODS: This retrospective study
      included 401 naive HBeAg-positive chronic hepatitis B patients who were treated
      with LAM 100 mg daily for at least 24 weeks (range 24-258 weeks). Among them, 124
      patients who achieved a complete response (HBeAg seroconversion, alanine
      aminotransferase normalization, hepatitis B virus DNA < 200 copies/ml) at the end
      of LAM therapy were followed up for at least 48 weeks (range 48-350 weeks).
      RESULTS: Of the 124 complete responders, 42 (33.87%) achieved a sustained
      response (persistent response >or= 48 weeks). However, the cumulative relapse
      rates at 48 and 96 weeks post-treatment were 54.03% and 68.4%, respectively.
      Multivariate analysis revealed pretreatment age <or= 34 years [hazard ratio (HR)
      2.25; 95% confidence interval (CI) 1.40-3.62; p < 0.001] and LAM consolidation
      therapy >or= 48 weeks (HR 2.44; 95% CI 1.35-4.40; p = 0.003) to be independent
      factors for predicting a sustained response. CONCLUSIONS: LAM-induced HBeAg
      seroconversion is not durable in Taiwan. However, a duration of LAM consolidation
      therapy > 48 weeks may be favorable for maintaining durable HBeAg seroconversion.

PMID- 20030581
TI  - Prevention of covered enteral stent migration in patients with malignant gastric
      outlet obstruction: a pilot study of anchoring with endoscopic clips.
AB  - OBJECTIVE: Placement of a self-expandable metal stent is a palliative treatment
      of choice for patients with malignant gastric outlet obstruction (GOO). Although
      covering an enteral stent with a membrane almost solves the problem of tumor
      ingrowth, stent migration continues to be a major unresolved problem. Our aim was
      to evaluate the clinical efficacy of endoscopic clipping for prevention of
      covered stent migration in the treatment of malignant GOO. MATERIAL AND METHODS:
      A total of 25 consecutive patients with malignant GOO were evaluated
      prospectively. After deployment of a double-layered combination stent (comprising
      an outer uncovered stent and an inner covered stent), three endoscopic clips were
      applied for fixation of the proximal end of the enteral stent to the gastric or
      duodenal mucosa. RESULTS: Technical and clinical success rates were 100% (25/25)
      and 88% (22/25), respectively. No stent migration was observed in any of the
      patients. Five patients (20%) experienced complications such as tumor overgrowth
      and stent compression. CONCLUSION: Endoscopic clipping for enteral stent
      placement seems to be effective for prevention of covered stent migration in
      patients with malignant GOO.

PMID- 20030582
TI  - Ubiquitin ligase complexes: from substrate selectivity to conjugational
      specificity.
AB  - Localization, activity and lifespan of a protein are signaled by a small, 8 kDa
      protein, ubiquitin (Ub). Ub conjugation is a post-translational modification
      orchestrated by the sequential action of activating (E1), conjugating (E2), and
      ligating (E3) enzymes. Although a simple combination of an E2 and an E3 enzyme
      can be sufficient for an active complex, in other cases ubiquitination can occur
      in the context of large multimeric complexes with enhanced molecular abilities.
      Here, we review several Ub ligase complexes to highlight strategies governing
      conjugational specificity, the gained adaptability in substrate specificity, and
      modulatory flexibility encoded in regulatory components of these diverse
      multimers.

PMID- 20030583
TI  - Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human
      cell infection: insights into new synthetic subunit vaccine candidates.
AB  - Mycobacterium tuberculosis infection continues to be a major cause of morbidity
      and mortality throughout the world. The vast complexity of the intracellular
      pathogen M. tuberculosis and the diverse mechanisms by which it can invade host
      cells highlight the importance of developing a fully protective vaccine. Our
      vaccine development strategy consists of including fragments from multiple
      mycobacterial proteins involved in cell invasion. The aim of this study was to
      identify high activity binding peptides (HABPs) in the immunogenic protein
      Rv1980c from M. tuberculosis H37Rv with the ability to inhibit mycobacterial
      invasion into U937 monocyte-derived macrophages and A549 cells. The presence and
      transcription of the Rv1980c gene was assessed in members belonging to the M.
      tuberculosis complex and other nontuberculous mycobacteria by PCR and RT-PCR,
      respectively. Cell surface localization was confirmed by immuno-electron
      microscopy. Three peptides binding with high activity to U937 cells and one to
      A549 cells were identified. HABPs 31100, 31101, and 31107 inhibited invasion of
      M. tuberculosis into A549 and U937 cells and therefore could be promising
      candidates for the design of a subunit-based antituberculous vaccine.

PMID- 20030584
TI  - Signal transduction in CHO cells stably transfected with domain-selective forms
      of murine ACE.
AB  - Membrane-bound human angiotensin-converting enzyme (ACE) has been reported to
      initiate intracellular signaling after interaction with substrates or inhibitors.
      Somatic ACE is known to contain two distinct, extracellular catalytic centers. We
      analyzed the signal transduction mechanisms in cells transfected with different
      forms of murine ACE (mACE) and investigated whether the two domains are similarly
      involved in these processes. For this purpose, CHO cells were stably transfected
      with mACE or with its domain-selective mutants. In addition to these modified
      cellular models, human umbilical vein endothelial cells were used in this study.
      Signal transduction molecules such as JNK and c-Jun were analyzed after
      activation of cells with several ACE substrates and inhibitors. ACE-targeting
      compounds such as substrates, inhibitors, or even the ACE product angiotensin-II
      induce in mACE-expressing cells a signal transduction response. These processes
      are also evoked by partially inactivated forms of mACE and finally result in an
      enhanced cyclooxygenase-2 transcription. Surprisingly, the membrane-bound ACE
      activity is also influenced by ACE-targeted interventions. Our data suggest that
      the two catalytic domains of mACE do not function independently but that the
      signal transduction is influenced by negative cooperativity of the two catalytic
      domains. This study underlines that ACE indeed has receptor-like properties which
      occur in a species-specific manner.

PMID- 20030585
TI  - The epimerase activity of anthocyanidin reductase from Vitis vinifera and its
      regiospecific hydride transfers.
AB  - Anthocyanidin reductase (ANR) from Vitis vinifera catalyzes an NADPH-dependent
      double reduction of anthocyanidins producing a mixture of (2S,3R)- and (2S,3S)
      flavan-3-ols. At pH 7.5 and 30 degrees C, the first hydride transfer to
      anthocyanidin is irreversible, and no intermediate is released during catalysis.
      ANR reverse activity was assessed in the presence of excess NADP(+). Analysis of
      products by reverse phase and chiral phase HPLC demonstrates that ANR acts as a
      flavan-3-ol C(3)-epimerase under such conditions, but this is only observed with
      2R-flavan-3-ols, not with 2S-flavan-3-ols produced by the enzyme in the forward
      reaction. In the presence of deuterated coenzyme 4S-NADPD, ANR transforms
      anthocyanidins into dideuterated flavan-3-ols. The regiospecificity of deuterium
      incorporation into catechin and afzelechin - derived from cyanidin and
      pelargonidin, respectively - was analyzed by liquid chromatography coupled with
      electro- spray ionization-tandem mass spectrometry (LC/ESI-MS/MS), and it was
      found that deuterium was always incorporated at C(2) and C(4). We conclude that
      C(3)-epimerization should be achieved by tautomerization between the two hydride
      transfers and that this produces a quinone methide intermediate which serves as
      C(4) target of the second hydride transfer, thereby avoiding any stereospecific
      modification of carbon 3. The inversion of C(2) stereochemistry required for
      'reverse epimerization' suggests that the 2S configuration induces an
      irreversible product dissociation.

PMID- 20030587
TI  - Antibacterial activity of radical scavengers against class Ib ribonucleotide
      reductase from Bacillus anthracis.
AB  - Bacillus anthracis is a severe mammalian pathogen. The deoxyribonucleotides
      necessary for DNA replication and repair are provided via the ribonucleotide
      reductase (RNR) enzyme. RNR is also important for spore germination and cell
      proliferation upon infection. We show that the expression of B. anthracis class
      Ib RNR responds to the environment that the pathogen encounters upon infection.
      We also show that several anti-proliferative agents (radical scavengers)
      specifically inhibit the B. anthracis RNR. Owing to the importance of RNR in the
      pathogenic infection process, our results highlight a promising potential to
      inhibit the growth of B. anthracis early during infection.

PMID- 20030586
TI  - An examination of the proteolytic activity for bovine pregnancy-associated
      glycoproteins 2 and 12.
AB  - The pregnancy-associated glycoproteins (PAGs) represent a complex group of
      putative aspartic peptidases expressed exclusively in the placentas of species in
      the Artiodactyla order. The ruminant PAGs segregate into two classes: the
      'ancient' and 'modern' PAGs. Some of the modern PAGs possess alterations in the
      catalytic center that are predicted to preclude their ability to act as
      peptidases. The ancient ruminant PAGs in contrast are thought to be peptidases,
      although no proteolytic activity has been described for these members. The aim of
      the present study was to investigate (1) if the ancient bovine PAGs (PAG-2 and
      PAG-12) have proteolytic activity, and (2) if there are any differences in
      activity between these two closely related members. Recombinant bovine PAG-2 and
      PAG-12 were expressed in a baculovirus expression system and the purified
      proteins were analyzed for proteolytic activity against a synthetic fluorescent
      cathepsin D/E substrate. Both proteins exhibited proteolytic activity with acidic
      pH optima. The k(cat)/K(m) for bovine PAG-2 was 2.7x10(5) m(-1) s(-1) and for
      boPAG-12 it was 6.8x10(4) m(-1) s(-1). The enzymes were inhibited by pepstatin A
      with a K(i) of 0.56 and 7.5 nm for boPAG-2 and boPAG-12, respectively. This is
      the first report describing proteolytic activity in PAGs from ruminant ungulates.

PMID- 20030588
TI  - Analysis of an autoproteolytic activity of rice yellow mottle virus silencing
      suppressor P1.
AB  - Ectopically expressed rice yellow mottle virus P1 fusion proteins were found to
      be cleaved in planta and in Escherichia coli. Cleavage takes place in the absence
      of bacterial protease activity, indicating that the P1 fusion is
      autocatalytically processed independently of host factors. N-terminal sequencing
      of the C-terminal cleavage product of transiently expressed P1/GFP (green
      fluorescence protein) in Nicotiana benthamiana showed that the cleavage site is
      located between the first two amino acids (aa) downstream of the P1 sequence.
      Mutagenesis experiments revealed that a phenylalanine to valine substitution at
      position 157 of the P1 aa sequence impairs proper cleavage, which is nearly
      unaffected by replacement of phenylalanine with tyrosine. Deletion of
      methionine(159) (first GFP aa residue) appeared to not affect P1/GFP cleavage. N
      terminal P1-tagging with GFP turned out to impair autocleavage, whereas a small
      His-tag could not fully prevent cleavage. Additionally, a modified P1/GFP
      carrying an N-terminal deletion of 81 aa was not cleaved. These findings indicate
      that this region is involved in the proteolysis mechanism and that large N
      terminal fusion partners might affect correct folding of the P1 necessary for
      self-catalysis.

PMID- 20030589
TI  - 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent
      synthesis of small de novo products.
AB  - 6S RNA from Escherichia coli is known to bind to RNA polymerase, preventing
      interaction with many promoters during stationary growth. The resulting
      repression is released under conditions of nutritional upshift, when the growth
      situation improves. 6S RNA, which binds to the active site of RNA polymerase, has
      the particularly interesting feature to act as a template, causing the
      transcription of defined de novo RNAs (dnRNA) that are complementary to a
      specific sequence region of the 6S RNA. We analyzed the conditions of dnRNA
      synthesis and determined their effect on the 6S RNA-mediated inhibition of RNA
      polymerase in vitro and in vivo. Upon nutritional upshift the RNA polymerase/6S
      RNA complex induces the rapid synthesis of dnRNAs, which form stable hybrids with
      the 6S RNA template. The resulting structural change destabilizes the inactivated
      RNA polymerase complex, causing sigma subunit release. Both dnRNA and 6S RNA are
      rapidly degraded after complex disintegration. Experiments using the
      transcriptional inhibitor rifampicin demonstrate that active transcription is
      required for the disintegration of the RNA polymerase/6S RNA complex. Our results
      support the conclusion that 6S RNA not only inhibits transcription during
      stationary growth but also enables cells to resume rapid growth after starvation
      and help to escape from stationary phase.

PMID- 20030590
TI  - Phosphorylase and the origin of reversible protein phosphorylation.
AB  - This article presents a historical account of the discovery of reversible protein
      phosphorylation. The process was uncovered in the mid-1950s in a study designed
      to elucidate the complex hormonal regulation of skeletal muscle glycogen
      phosphorylase. This enzyme was originally thought to be regulated by AMP now
      known to serve as an allosteric effector. By contrast, hormonal regulation was
      found to result from a phosphorylation of the protein triggered by Ca(2+) and ATP
      which activate phosphorylase kinase; the reverse reaction is catalyzed by a
      phosphorylase phosphatase. Although that reaction is extremely simple, it came
      nevertheless as a complete surprise because essentially nothing was known at that
      time about the structure and function of phosphoproteins. This study led to the
      establishment of the first hormonal cascade of successive enzymatic reactions,
      kinases acting on kinases, initiated by cAMP discovered by Earl Sutherland. It
      also showed how two different physiological processes (carbohydrate metabolism
      and muscle contraction) could be regulated in concert. The regulation of
      phosphorylase was so straightforward that it was thought to represent the
      prototype for these kinds of interconversions. We know today that it was almost
      the absolute exception.

PMID- 20030591
TI  - beta-Catenin as a multilayer modulator of zonal cytochrome P450 expression in
      mouse liver.
AB  - The liver is the major organ for metabolism of drugs and other xenobiotics.
      Expression of many drug-metabolizing enzymes is not equally distributed
      throughout the liver: under normal conditions, many of them, including the most
      relevant members of the cytochrome P450 superfamily, are exclusively expressed in
      a hepatocyte subpopulation located near branches of the efferent central vein.
      Activation of different ligand-dependent transcription factors by exogenous
      compounds stimulates high expression of certain cytochrome P450 isoforms. This
      process also occurs preferentially in perivenous hepatocytes. The mechanisms,
      however, which determine the zone-specificity of basal and xenobiotic-induced
      expression of cytochrome P450 enzymes, have remained largely unknown for decades.
      Very recently, signaling through the Wnt/beta-catenin pathway has been implicated
      in the regulation of zonal gene expression in mouse liver. In this review,
      current knowledge of cytochrome P450 regulation by beta-catenin-dependent
      transcription is summarized and underlying molecular mechanisms are discussed.

PMID- 20030592
TI  - Principles, implementation, and application of biology-oriented synthesis (BIOS).
AB  - Biology-oriented synthesis (BIOS) represents an alternative approach for the
      generation of compound collections for biological applications. In BIOS,
      biologically relevant and prevalidated scaffold structures, such as core
      structures of natural products or known drugs, are employed as scaffolds for the
      generation of compound collections with focused diversity. In this review, we
      discuss the underlying concept of the BIOS approach, and its practical
      implementation in library design and synthesis. To highlight its relevance for
      chemical biology applications, we finally present examples in which compound
      collections generated under the BIOS principle have been used to elucidate
      biological questions.

PMID- 20030593
TI  - The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic
      responses in dolphin skin cells.
AB  - The Atlantic bottlenose dolphin has been the focus of much attention owing to the
      considerable impact of environmental stress on its health and the associated
      implications for human health. Here, we used skin cells from the dolphin to
      investigate the protective role of the vitamin D pathway against environmental
      stressors. We previously reported that dolphin skin cells respond to 1,25
      dihydroxyvitamin D3 (1,25D3), the bioactive metabolite of vitamin D3, by
      upregulation of the vitamin D receptor (VDR) and expression of several genes.
      Methylmercury is a highly bioaccumulative environmental stressor of relevance to
      the dolphin. We currently report that in dolphin cells sublethal concentrations
      of methylmercury compromise the ability of 1,25D3 to upregulate VDR, to
      transactivate a vitamin D-sensitive promoter, and to express specific target
      genes. These results help elucidate the effects of vitamin D and methylmercury on
      innate immunity in dolphin skin and potentially in human skin as well,
      considering similarities in the vitamin D pathway between the two species.

PMID- 20030594
TI  - Advanced oxidation protein products as an oxidative stress marker in allergic
      rhinitis.
AB  - OBJECTIVES: This study was designed to compare the levels of dityrosine
      containing protein cross-link products, also known as advanced oxidation protein
      products (AOPP); in patients with allergic rhinitis with those in healthy
      individuals considering the fact that AOPP has the potential to be a marker of
      oxidative stress specific to proteins in mammalian systems. PATIENTS AND METHODS:
      This study was performed on 40 patients (18 males, 22 females; mean age 29 years;
      range 10 to 53 years) with allergic rhinitis admitted to our clinic between
      December 2008 and January 2009 and on 40 healthy volunteers (16 males, 24
      females; mean age 31 years; range 13 to 48 years). Skin prick test was performed
      to establish a diagnosis of allergic rhinitis in patients with major symptoms and
      allergic sensitization was also supported with serum IgE levels. Blood samples
      were obtained and examined in all patients to determine AOPP. RESULTS: Serum AOPP
      levels were significantly higher in patients with allergic rhinitis (169.0+/-14.2
      micromol/L) compared to controls (43.9+/-3.5 micromol/L; p<0.001). In addition,
      mean serum IgE levels of patients with allergic rhinitis (308.2+/-38.5 IU/ml)
      were found to support the presence of allergic sensitization. CONCLUSION:
      Determining the levels of serum AOPP, a well-known marker of protein oxidation,
      appears to be a useful method in determining the role of oxidative stress in the
      etiopathogenesis of allergic rhinitis.

PMID- 20030595
TI  - [The incidence of group A beta haemolytic streptococci in upper respiratory tract
      infections in Erzurum].
AB  - OBJECTIVES: The incidence of group A beta hemolytic streptococci (GABHS) in upper
      respiratory tract infections in Erzurum was investigated. PATIENTS AND METHODS:
      In this descriptive study throat swabs were obtained from 4112 patients (1989
      males, 2123 females; mean age 21+/-1.5 years; range 14 to 46 years) with upper
      respiratory tract infections in Erzurum, Turkey between January 2006 and December
      2006 and they were cultured for isolation of GABHS. RESULTS: In this study GABHS
      were isolated in 268 (6.51%) of patients. Group A beta hemolytic streptococci
      were isolated in 51 of 941 patients (5.42%) in the spring, in 23 of 592 patients
      (3.88%) in the summer, in 69 of 968 patients (7.13%) in the autumn, and in 125 of
      1611 patients in the winter. Of those patients in whom GABHS were isolated, 128
      (6.43%) were male and 140 (6.59%) were female. At Chi square test, (Range for
      alpha value, p=0.01 and p=0.05) there was a significant difference in the
      frequency of infection between the seasons (p<0.01). There was no significant
      difference between men and women with respect to carrier rate (p>0.05).
      CONCLUSION: The incidence of GABHS detected in Erzurum was lower than that in
      other countries. There were statistically significant differences in frequency
      between the seasons (p<0.01). The highest incidence was in the winter. Low
      incidence of GABHS in this region may be due to prevention of the colonization
      because of geographic features, nutritional habits and other factors.

PMID- 20030596
TI  - The effectiveness of nasal decongestants, oral decongestants and oral
      decongestant-antihistamines in the treatment of acute otitis media in children.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of nasal
      decongestants, oral decongestants and oral decongestant-antihistamines in the
      treatment of acute otitis media and resolution of the middle ear effusion in
      children. PATIENTS AND METHODS: 355 ears of 318 children [160 boys (179 ears) and
      158 girls (176 ears)] who were diagnosed to have acute otitis media and treated
      for it with different drug regimens were evaluated retrospectively regarding
      resolution of the middle ear fluid. 151 ears were treated with antibiotics and
      analgesics (group 1), 64 with antibiotics, topical decongestants and analgesics
      (group 2), 81 with antibiotics, oral decongestants and analgesics (group 3), and
      59 with antibiotics, oral decongestant-antihistamine combinations and analgesics
      (group 4). The children with middle ear effusion were followed up for three
      months. RESULTS: Group 1, 2, 3 and 4 had persistent middle ear effusion and the
      presence of middle ear effusion was 27.2%, 18.8%, 25.9%, 28.8% at the 1st month
      and 5.8%, 0%, 0% and 5.9% at the end of the 3rd month, respectively. At the end
      of the 3rd month, there was no significant difference between the groups
      regarding the resolution rates of the middle ear fluids in the antibiotic group
      and decongestants groups (p>0.05). CONCLUSION: We do not recommend the use of
      decongestants and antihistamines in the treatment of acute otitis media as they
      do not change the natural course of the disease.

PMID- 20030597
TI  - [The importance of computed tomography examination of temporal bone in detecting
      tympanosclerosis].
AB  - OBJECTIVES: The aim of this study was to show detectability of tympanosclerotic
      plaques with computed tomography (CT) which has an important role in the
      evaluation of temporal bone. PATIENTS AND METHODS: Our study group included 19
      tympanoplasty cases (12 females, 7 males; mean age 31 years; range 12 to 57
      years) who were operated on for hearing restoration due to chronic otitis media
      and conductive hearing loss between January 2006 and May 2006 at the Department
      of Otolaryngology, Head and Neck Surgery, Izmir Ataturk Training and Research
      Hospital. The tympanosclerotic plaques obtained from surgical specimens were sent
      for pathological confirmation and temporal bone CT scans which were obtained
      preoperatively were reevaluated by a blinded radiologist who was dealing with
      head and neck radiology. RESULTS: All histopathological specimens obtained from
      tympanosclerotic plaques showed hyaline degeneration and increased collagen
      formation, resulting in increased epithelial thickness, calcification and in some
      cases ossification. Tympanosclerosis was identified in CT scans as ossified or
      calcified high density regions in the soft tissue in middle ear cavity, leading
      to ovoid, linear or weblike forms. Of those 19 cases, who were unilaterally
      operated on, eight cases had findings suggestive of tympanosclerosis in CT only
      in tympanic membrane (42.1%), two in only middle ear (10.5%) and eight in both
      middle ear and tympanic membrane (42.1%). In only one case (5.2%),
      tympanosclerosis was not identified radiologically. CONCLUSION: This study shows
      that temporal bone CT scan is a valuable method to diagnose the etiology of
      hearing loss and to detect the localization of the tympanosclerosis, in patients
      with chronic otitis media and conductive hearing loss. When combined with
      clinical findings, CT scans can be an informative guide to otolaryngologists for
      preoperative evaluation of tympanosclerosis.

PMID- 20030598
TI  - [Total thyroidectomy in benign thyroid diseases].
AB  - OBJECTIVES: In this retrospective study, we reviewed the data from patients who
      had total thyroidectomy for benign thyroid disease and evaluated the safety of
      this surgery. PATIENTS AND METHODS: Three hundred and twenty three patients (49
      males, 274 females; mean age 42.6+/-14.1 years; range 13 to 80 years) who
      underwent total thyroidectomy between 2002 and 2008 were included in the study.
      In the preoperative studies, patients with suspicion of thyroid cancer were
      excluded. Indications for total thyroidectomy, cancer incidence and complication
      rates were evaluated. Two hundred and eighty three patients (87.6%) were operated
      on due to bilateral multinodular goiter, 17 (5.3%) due to toxic goiter, 23 (7.1%)
      due to thyroiditis. RESULTS: In our study, it was found that the incidences of
      permanent recurrent laryngeal nerve palsy and permanent hypoparathyroidism were
      0.6% and 1.86%, respectively. Postoperative hemorrhage requiring repeat surgery
      occurred in 0.6% of the patients. There was no recurrence during follow-up.
      CONCLUSION: The present study shows that total thyroidectomy is a safe procedure
      with a low incidence of permanent complications. Total thyroidectomy is an
      acceptable surgical alternative for benign multinodular or diffuse goiters.

PMID- 20030599
TI  - Cutaneous horn on the upper lip associated with squamous cell carcinoma.
AB  - Cutaneous horn is a protrusion from the skin consisting of cornified material. It
      usually appears on exposed skin areas especially on the head and neck. A 70-year
      old woman applied to our clinic with a hard, conical, black-grey 2 cm lesion on
      the upper lip. On physical examination, there was no palpable lymph node in the
      neck other than the lesion. Diagnosed to be cutaneous horn, the lesion was
      completely removed together with 4-5 mm surrounding tissues under local
      anaesthesia. The histopathological examination reported this lesion to be
      cutaneous horn with well differentiated squamous cell carcinoma at its base. No
      recurrences or metastasis were detected within a follow-up period of 5.5 years.
      It should be kept in mind that cutaneous horns may be associated with
      premalignant and malignant lesions at the base, masking numerous conditions.

PMID- 20030600
TI  - [Foreign body which resembles concha bulloza in the middle meatus: a case
      report].
AB  - Diagnosis of foreign body in the nasal cavity may be difficult because it has a
      wide variety of presentations. Concha bullosa is defined as the pneumatization of
      the middle concha in various degrees. A 43-year-old female patient was admitted
      to our clinic with the complaint of breathing difficulty through her right
      nostril which had been going on for the last year. She had had some medical
      treatments previously in some different medical centers, there wasn't purulent
      discharge with unpleasant odour, bleeding and halitosis in the nose and there
      wasn't a history of a blow to the nose or a history of previous facial, nasal or
      dental surgery. In the computed tomography there was an image resembling concha
      bullosa. Transnasal endoscopic approach was used, under general anesthesia, in
      the patient, whose physical examination results, laboratory findings and allergy
      test results were normal. Endoscopic sinus surgery was performed including
      polypectomy, right uncinektomy and the foreign body was removed from the middle
      meatus using a forceps. No complications were observed in the follow-up control
      one month later.

PMID- 20030601
TI  - [Zenker diverticulum: a case report].
AB  - Zenker's diverticulum is a pulsion typed pharyngoeosophageal diverticle caused by
      the herniation of the pharyngeal mucosa, standing beside the posterior pharyngeal
      wall, through the Killian opening which is known as the weak area between the
      inferior constructor muscle's oblique fibres and transverse fibres of
      cricopharyngeal muscle. In patients with Zenker's diverticulum, symptoms such as
      disfagia, globus in the cervical area, weigh loss, regurgitation, cough, and
      aspiration. These patients are primarily admitted to the Gastroenterology and
      Othorhinolaryngology clinics with the complaint of disfagia and the diagnosis of
      this disease is mostly established late and the treatment is started late because
      the results of their physical examinations seem normal. Therefore, especially in
      the patients who have disfagia complaint, pharyngoeosophageal diverticle
      prediagnosis should be thought and that should be examined by passage graphies
      with barium and endoscopic methods, if needed. In this article, we presented the
      67-year-old Zenker's diverticulum patient in whom we performed open
      diverticulectomy and posterior cricopharyngeal myotomy, and we specified the
      important points in choosing the patient and the type of surgery.

PMID- 20030609
TI  - Neuropeptide receptors in intestinal disease: physiology and therapeutic
      potential.
AB  - The autonomous nervous system of the gut is increasingly recognized as an
      important regulatory factor in intestinal permeability and immune cell
      activation. Neuropeptides released by neurons -or inflammatory cells- have
      emerged as neuro-immune modulators that can relay, for instance, stress-induced
      neuronal activity to immune processes. Such peptides can participate in processes
      reducing inflammatory responses, or augment resolution of inflammation.
      Neuropeptides and hormones such as vasoactive intestinal peptide, urocortin,
      ghrelin, and cortistatin have been shown to modulate the disease activity in a
      variety of experimental models of inflammatory and autoimmune disease via
      modulation of immune or neuronal cell activity. We review here the potential of
      neuropeptide receptor activation to modulate inflammatory diseases of the
      intestine. We will highlight the role of neuropeptides in gastrointestinal (GI)
      physiology and immune regulation, and we will speculate on the therapeutic
      potential of peptides that bind G protein coupled receptors (GPCRs) in the
      management of inflammation in the GI tract.

PMID- 20030610
TI  - Peptide antagonist of the androgen receptor.
AB  - Androgen receptor (AR) is a steroid hormone receptor that is activated by
      endogenous androgens, mainly testosterone and 5alpha-dihydrotestosterone (5alpha
      DHT). AR is also an important drug target, and AR antagonists (antiandrogens)
      have been widely used for prostate cancer therapy. Antiandrogens currently
      available on the market are all small molecules that antagonize AR function via
      binding to the ligand binding domain (LBD). AR peptide antagonist has been
      proposed as a 'mechanism-based' approach to directly block AR function by
      interrupting AR-protein interactions from the surface of the receptor. Without
      targeting the rigid ligand binding pocket within LBD, peptide antagonists allow
      more flexibility in structure design, and are likely to provide more efficient
      and complete blockade of AR function as compared to small molecule antagonists.
      AR interacts with a variety of proteins, and the interaction may be mediated by
      different functional domains of the receptor. Although varieties of AR-protein
      interfaces might serve as the target for peptide antagonist, majority of ongoing
      research is still focusing on peptides that target the LBD, which is mainly due
      to the abundance of structural information revealed by crystal structures. This
      review gives an overview of the current research attempts to develop AR peptide
      antagonists, particularly peptide antagonists that target the LBD and N-terminal
      domain (NTD). The challenges and opportunities for future discovery and
      development of peptide antagonists are discussed as well.

PMID- 20030611
TI  - Emerging peptide therapeutics for inflammatory autoimmune diseases.
AB  - Current pharmacologic treatments for inflammatory diseases are largely palliative
      rather than curative. Most of them result in nonspecific immunosuppression. This
      can be associated with disruption of natural and induced immunity with
      significant, sometimes dramatic, adverse effects. Among the novel strategies that
      are under development, tools that target specific molecular pathways and cells,
      and more precisely modulate the immune system to restore normal tolerance
      mechanisms are central. In these approaches, peptide therapeutics constitute a
      valuable class of therapeutic agents. They possess a number of intrinsic
      properties that are favorable for long-term treatments. They are also versatile
      components that can be modified to improve their capacities without affecting
      their bioactivity. Peptide-mediated immunotherapy has been evaluated in several
      appropriate experimental animal models. A few peptides are currently evaluated in
      clinical trials for the treatment of human chronic inflammatory diseases. In this
      review we describe a number of these emerging peptide therapeutics. We also
      discuss future challenges that, in addition to include selection of appropriate
      peptide drugs, also involve the optimization of peptide dosage and route of
      administration as well as the improvement of peptide stability for adequate
      bioavailability and specific targeting.

PMID- 20030612
TI  - Peptides targeting Toll-like receptor signalling pathways for novel immune
      therapeutics.
AB  - Toll-like receptors (TLRs) are a family of key proteins that permit mammals to
      detect microbes and endogenous molecules, which are present in body fluids, cell
      membranes and cytoplasm. They confer mechanisms to the host for maintaining
      homeostasis, activating innate immunity and inducing signals that lead to the
      activation of adaptive immunity. TLR signalling induces the expression of pro
      inflammatory and anti-viral genes through different and intricate pathways.
      However, persistent signalling can be dangerous and all members of the TLR family
      are involved in the pathogenesis of acute and chronic inflammation, autoimmunity,
      allergy, cancer and aging. The pharmaceutical industry has begun intensive work
      developing novel immunotherapeutic approaches based on both activation and
      inhibition of TLR triggering. Further, clinical trials are pending to evaluate
      TLR agonists as novel vaccine adjuvants and for the treatment of infectious
      diseases, allergic diseases and asthma. Since systemic, metabolic and
      neuroendocrine changes are elicited by inflammation, TLR activity is susceptible
      of regulation by hormones and neuroendocrine factors. Neuroendocrine mediators
      are important players in modulating different phases of TLR regulation
      contributing to the endogenous control of homeostasis through local, regional and
      systemic routes. Vasoactive intestinal peptide (VIP) is an important signal
      molecule of the neuroendocrine-immune network that has recently emerged as a
      potential candidate for the treatment of inflammatory and autoimmune disorders by
      controlling innate and adaptive immunity. This review shows current advances in
      the understanding of TLR modulation by VIP that could contribute to the use of
      this natural peptide as a therapeutic tool.

PMID- 20030613
TI  - Peptide-based inhibitors of the HIV envelope protein and other class I viral
      fusion proteins.
AB  - Viruses need to deliver their genomic information into the host cell lumen to
      establish productive infection. Enveloped viruses accomplish this task by fusing
      their membrane with a host cell membrane. Membrane fusion is facilitated by
      specialized viral membrane proteins, which mediate binding and entry into host
      cells. The architecture of the fusion machinery of envelope proteins can differ
      between viruses, and class I, II and III fusion systems have been described.
      However, the conformational rearrangements associated with membrane fusion are
      comparable and constitute attractive targets for intervention. The fusion
      apparatus of the human immunodeficiency virus (HIV) envelope protein (Env), a
      class I fusion protein, is located in the transmembrane unit gP41 of Env. The
      fusion machinery is activated by Env binding to CD4 and a chemokine coreceptor,
      and the structural rearrangements in gp41 associated with membrane fusion
      comprise the insertion of a fusion peptide into the target cell membrane and the
      formation of a stable six-helix bundle structure. These processes can be
      efficiently inhibited by peptides mimicking conserved functional elements in
      gp41. A prominent example for such peptides, termed fusion inhibitors, is the
      peptide T-20 (enfuvirtide, Fuzeon) which is used as salvage therapy of HIV/AIDS.
      Here, we will discuss how HIV mediates fusion with host cell membranes and how
      this process can be blocked by peptides targeting gp41. In addition, we will
      discuss peptide inhibitors of other class I viral fusion proteins.

PMID- 20030614
TI  - Antimicrobial peptides present in mammalian skin and gut are multifunctional
      defence molecules.
AB  - Antimicrobial peptides are major components of the innate immune defence. They
      are well conserved along evolution, non-toxic and they ensure potent defences
      against a large number of pathogens. They act by direct killing of microorganisms
      and they possess additional roles in the regulation of adaptive immune responses,
      by recruting or stimulating immune cells. Skin and gut are positioned at the
      interface of internal milieu and external environment. They represent a physical
      and chemical barrier against pathogens invasion and the antimicrobial peptides
      limit pathogen growth in normal conditions. During infection or injury, some of
      these peptides are overexpressed and disrupt microbial membranes and/or stimulate
      immune cell recruitment, allowing to return to homeostasis or to increase
      inflammation. Antimicrobial peptides expression is altered in several diseases:
      alpha-defensins deficiency is related with Crohn's disease and in skin,
      cathelicidin LL-37 and beta-defensin-2 are overexpressed in psoriasis, while in
      atopic dermatitis, their expression is decreased. The present review provides an
      up-to-date summary of the expression and the biological roles of the
      antimicrobial peptides found in the skin and gastrointestinal mucosa of the host,
      in normal and pathological conditions. The involvement of these natural
      antimicrobial peptides in inflammation, is also discussed.

PMID- 20030615
TI  - Cyclic nucleotide phosphodiesterases (PDE) and peptide motifs.
AB  - Cyclic nucleotide phosphodiesterase (PDE), that is a multigenic enzyme
      superfamily ubiquitously distributed in mammalians, mainly contributes to
      intracellular signaling regulation. Its various isozymes specifically control in
      a spatio-temporal manner intracellular levels of cAMP and cGMP downstream
      receptor activation and nearby functional proteins. The PDE superfamily is
      constituted by 11 gene families (PDE1-PDE11), comprising 21 genes represented by
      more than 100 mRNA products due to alternative splicing. Among them, PDE3, PDE4
      and PDE5 were viewed as therapeutic targets and therefore, due to the successful
      development of Viagra (sildenafil, potent selective PDE5 inhibitor), the
      knowledge in PDE field burst out with the help of academic/pharmaceutical
      collaborations. Organic medicinal chemistry, using crystallographic and docking
      approaches, has focused its search on the catalytic pocket of PDEs, leaving aside
      the development of variant subtype specific PDE inhibitors and activators. This
      review firstly describes the various properties of each PDE isozyme, focusing
      particularly on their regulatory domains, mainly located in the N-terminus.
      Thereafter, we review the possible peptidic regulations of PDE activity itself,
      then the PDE anchoring in macromolecular complexes and finally the direct
      interaction of PDE with some critical intracellular proteins, such as beta
      arrestin, immunophilin and proteins containing SH3-domain. Altogether, it appears
      that a peptidic approach would be helpful to study the intrinsic PDE regulation
      of each subfamily, and thereafter the PDE peptidic motifs implicated as well as
      PDE location in signaling cascades. Taking in account the various regulatory PDE
      domains could lead to design new peptides to conceive variant specific inhibitors
      as well as activators in a therapeutical goal.

PMID- 20030616
TI  - Peptide-based matrices as drug delivery vehicles.
AB  - Peptides, polypeptides and proteins have been extensively studied for their
      various structural and functional roles in living organisms. However,
      breakthrough discoveries in the last decades identified some peptide-based
      matrices that posses the ability to traverse biological membranes, and many
      peptides, polypeptides and even complete proteins have been shown to have such
      properties. Hence, these matrices have been successfully used for the
      intracellular delivery of many therapeutic cargos including small molecules,
      proteins, peptides, oligonucleutides, plasmids and nanoparticles both in vitro
      and in vivo. Being neither toxic nor carcinogenic and meanwhile efficient in
      delivery, they are recognized as very promising vectors to overcome the
      shortcomings of the available technologies. The characteristics of these peptide
      based matrices and their applications in drug delivery are here briefly
      illustrated together with current challenges and future prospects.

PMID- 20030618
TI  - Toll-like receptors: cost or benefit for cancer?
AB  - The function of the Toll-like receptor (TLR) family members has been extensively
      studied in the recent decades. The TLR family is generally involved in the
      defense against microbial infections. TLRs are expressed mainly on macrophages
      and dendritic cells (DCs) and activate these cells upon ligand binding. The
      activation of TLRs basically initiates innate immune response, but can also
      induce adaptive immune response. TLRs have also been found on epithelial and
      tumor cells, but their role on tumor cells is still unclear. In some tumor types
      TLRs promote tumor proliferation and survival, while in others TLR2, -3 and -9
      have been shown to be directly involved in apoptosis. Therefore, they seem to be
      promising candidates for the development of new, effective therapeutic options.
      It is however necessary to conduct comprehensive studies to assess the
      significance of these receptors in neoplastic cells. TLR ligands can also be used
      as immunostimulatory molecules to boost immune system in anticancer treatment. In
      this respect TLRs have been used in numerous preclinical and clinical studies.
      However, adjuvants can evoke distinct immune responses, either beneficial or
      deleterious in the neoplastic setting. Moreover, neoplastic processes may also
      subvert different signaling pathways and thereby advance cancer progression. From
      both points of view careful selection of adjuvants is a necessary prerequisite
      for cancer patient's treatment. Thus, TLRs have a dual role, when used as a
      target for immunostimulation, as well as when used directly to kill the cancer
      cell.

PMID- 20030619
TI  - Development of agents that modulate protein-protein interactions in membranes.
AB  - Membrane proteins account for approximately one third of all proteins in
      eukaryotic and prokaryotic cells. These proteins are critical in a diverse array
      of cellular functions. Despite their obvious importance, the effectiveness of
      research tools to study the structure and function of integral membrane proteins
      lags behind that of water-soluble proteins. This is due in part to the lack of
      probing agents that can specifically and selectively recognize these targets.
      This review focuses on methods developed to overcome the obstacles of studying
      membrane proteins. We describe TM protein properties as well as biophysical
      properties of amino acids within the membrane bilayer. We also summarize the
      known characteristics of membrane regions in their distinctive environments and
      generate a summary of current research approaches that succeed in probing
      interactions of TM proteins within their native setting. This allows further
      insight into protein-protein interactions in a hydrophobic environment as it
      pertains to drug development.

PMID- 20030617
TI  - Peptidic tumor targeting agents: the road from phage display peptide selections
      to clinical applications.
AB  - Cancer has become the number one cause of death amongst Americans, killing
      approximately 1,600 people per day. Novel methods for early detection and the
      development of effective treatments are an eminent priority in medicine. For this
      reason, isolation of tumor-specific ligands is a growing area of research. Tumor
      specific binding agents can be used to probe the tumor cell surface phenotype and
      to customize treatment accordingly by conjugating the appropriate cell-targeting
      ligand to an anticancer drug. This refines the molecular diagnosis of the tumor
      and creates guided drugs that can target the tumor while sparing healthy tissues.
      Additionally, these targeting agents can be used as in vivo imaging agents that
      allow for earlier detection of tumors and micrometastasis. Phage display is a
      powerful technique for the isolation of peptides that bind to a particular target
      with high affinity and specificity. The biopanning of intact cancer cells or
      tumors in animals can be used as the bait to isolate peptides that bind to cancer
      specific cell surface biomarkers. Over the past 10 years, unbiased biopanning of
      phage-displayed peptide libraries has generated a suite of cancer targeting
      peptidic ligands. This review discusses the recent advances in the isolation of
      cancer-targeting peptides by unbiased biopanning methods and highlights the use
      of the isolated peptides in clinical applications.

PMID- 20030620
TI  - Metabolic targets of cardiac hormones' therapeutic anti-cancer effects.
AB  - The heart is a sophisticated endocrine gland synthesizing a family of peptide
      hormones by three different genes. These cardiac hormones are stored as 3
      prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide
      (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP
      prohormones are 4 peptide hormones, i.e. atrial natriuretic peptide, vessel
      dilator, kaliuretic peptide and long-acting natriuretic peptide (LANP) which
      decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and
      ovarian carcinomas as well as small-cell and squamous cell lung cancer cells
      within 24 hours in cell culture. In vivo these 4 cardiac hormones eliminate up to
      80% of human pancreatic adenocarcinomas, 2/3rds of human breast cancers, and up
      to 86% of human small-cell lung cancers in athymic mice. Their anticancer
      mechanism(s) target the Ras-MEK 1/2-ERK 1/2 kinase cascade in cancer cells. These
      4 cardiac hormones inhibit up to 95% of the basal activity of Ras, 98% of the
      phosphorylation of MEK 1/2 and 97% of the activation of basal activity of ERK
      1/2. They also completely block the activity of mitogens such as epidermal growth
      factor's ability to stimulate ERK. They do not inhibit the activity of ERK in
      healthy cells such as human fibroblasts. The final step in their anticancer
      mechanism of action is that they enter the nucleus as demonstrated by
      immunfluorescence to inhibit DNA synthesis within cancer cells.

PMID- 20030621
TI  - Development of opioid peptide analogs for pain relief.
AB  - Opioid receptors and opioid peptides constitute the endogenous opioid system. The
      most relevant function of the opioid system seems to be the inhibitory modulation
      of nociceptive information at supraspinal, spinal and peripheral sites, although
      it is also implicated in the modulation of many other processes in the body.
      Centrally acting plant opiates, such as morphine, are the most frequently used
      analgesics for the relief of severe pain, even though their undesired side
      effects are serious limitation to their usefulness. Opioid peptides have the
      potential to be pharmaceutical agents for the treatment of pain, devoid of side
      effects accompanying morphine. Unfortunately, peptides are generally hydrophilic
      compounds that will not enter the central nervous system via passive diffusion,
      due to the existence of the blood-brain barrier. Peptides are also easily
      degraded by proteolytic enzymes which further reduces their therapeutic value.
      Therefore, the design of peptide analogs based on the sequence of endogenous
      opioid peptides must be focused on increasing bioavailability and enhancing brain
      uptake.

PMID- 20030622
TI  - Role of dietary polyphenols in attenuating brain edema and cell swelling in
      cerebral ischemia.
AB  - Polyphenols are natural substances with variable phenolic structures and are
      enriched in vegetables, fruits, grains, bark, roots, tea, and wine. There are
      over 8000 polyphenolic structures identified in plants, but edible plants contain
      only several hundred polyphenolic structures. Recent interest in polyphenols has
      increased greatly due to their potential antioxidant effects. In addition, some
      polyphenols also have insulin-potentiating, anti-inflammatory, anti-carcinogenic,
      anti-viral, anti-ulcer, and anti-apoptotic properties although some of these
      properties may be a consequence of their anti-oxidant effects. Given that
      oxidative stress and inflammation are hypothesized to contribute to increased
      neural damage in ischemia, polyphenols appear to have a tremendous potential in
      attenuating such injuries. One important consequence of ischemia is brain edema
      and oxidative stress and inflammation are implicated in its pathogenesis. Brain
      edema is defined as an abnormal accumulation of fluid in the brain parenchyma
      resulting in a volumetric enlargement of the cells or tissue and can cause
      further ischemic damage. The purpose of this article is to review the current
      literature on brain edema and/or cell swelling in ischemic injury with the goal
      to identify newer approaches to attenuate brain edema. A review of currently
      known mechanisms underlying edema/cell swelling will be undertaken and the
      potential of dietary polyphenols to reduce edema will be critically reviewed with
      the discussion of some recent patents.

PMID- 20030623
TI  - Herbals and natural dietary supplements in psychiatric practice.
AB  - There is some evidence that links the increase of mental disorders' prevalence
      with a deterioration of Western countries' nutritional habits and it is found
      that the use of herbal and "natural" food supplements to treat different
      disorders is increasing. With factors such as chronic illness, poor health,
      emotional distress, and quality of life influencing the desire for complementary
      medicine, patients with comorbid medical and psychiatric problems seem likely to
      turn to this approach. We reviewed the most commonly used herbal and dietary
      supplements for which a certain efficacy on psychiatric symptoms or disorders has
      been claimed, checking current Pubmed-indexed literature (the most important
      being St. John's wort, Omega-3 fatty acids, valerian, Kava, Ginkgo, folate, B
      vitamins, SAMe, Inositol). There is an evidence of efficacy for some of these
      herbs an supplements, but current studies are often insufficient to reach a final
      conclusion; still patents are being requested and registered. Many different
      areas (including efficacy, tolerability, optimal dosing, adequate shelf life,
      drug and non-pharmacological interactions) need to be thoroughly studied;
      moreover political decisions need to be scientifically guided in order to best
      serve psychiatric patients' interests and to prevent the usage of expensive and
      sometimes un-useful therapies. This implies that a scientific strategy has to be
      used to rule out any third-part economical interest which could in any way
      influence therapeutic choices.

PMID- 20030625
TI  - Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity.
AB  - Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family of
      structurally related proteins that promote neuronal differentiation and survival
      during development, is a potent modulator of synaptic plasticity. Changes in BDNF
      expression, release and neuromodulatory activity, mediated by both epigenetic and
      post-translational mechanisms, have been associated with many pathological
      conditions and developmental experiences, such as maternal deprivation and
      environmental enrichment. Much effort has been devoted to studying plasticity in
      the hippocampus, a structure traditionally associated with learning and memory,
      yet there is increasing empirical support for the contribution of another
      structure--the amygdala--to BDNF-induced changes. Because the amygdala is a
      critical site for emotional memory formation, and many emotional and
      neurodevelopmental pathologies have been linked to amygdala-based abnormalities,
      considerable efforts have been devoted to the characterization of its circuitry.
      Here we review the role of BDNF as a biochemical integrator of convergent
      cellular signals, and as a central driver of neural plasticity. We conclude by
      emphasizing the importance of characterizing BDNF signaling cascades in
      behaviorally-relevant networks, to identify potential drug targets for novel
      therapeutic interventions.

PMID- 20030626
TI  - Molecular and cellular control of dendrite maturation during brain development.
AB  - Neuronal dendrites are generated during development by a series of processes
      involving extension and retraction of dendritic branches in a first step, and
      subsequently stabilisation of existing dendrites through building of synaptic
      connections. These processes are tightly controlled at any of these time points
      and control of dendritic development follows individual differentiation stages.
      This review describes aspects of the maturation process in cerebellar Purkinje
      cells and spinal motoneurons. Although motoneurons are glutamatergic whereas
      Purkinje cells are GABAergic and thereby functionally very different, dendritic
      maturation processes appear to share common mechanisms and processes in both
      neuronal cell types. Genetically-regulated cell-intrinsic processes control
      dendritic outgrowth at an early stage, being thereafter supported by local growth
      factors. In contrast, increasing synaptic input promotes dendritic maturation by
      limiting overgrowth at a later stage, with Ca2+-dependent signalling involving
      PKC or CaMKII as the common mode of action. This series of events apparently is
      common for other neuronal cell types suggesting a generalised concept for
      intercellular control of neuronal connectivity.

PMID- 20030627
TI  - The roles of I(D), I(A) and I(K) in the electrophysiological functions of small
      diameter rat trigeminal ganglion neurons.
AB  - The Kv currents are divided into three different K+ currents, such as slow
      inactivating transient K+ current (I(D)), fast inactivating transient K+ current
      (I(A)) and dominant sustained K+ current (I(K)), in small-diameter rat trigeminal
      ganglion (TG) neurons. The concentration of alpha-DTX (an I(D) blocker) to evoke
      the maximal inhibition of I(A) was 0.1 microM, and this concentration caused a 20
      % inhibition of I(A) and increased the number of action potentials. Irrespective
      of the presence of 0.1 microM alpha-DTX, the application of 0.5 mM 4-AP (an IA
      blocker) caused a 51 % inhibition of I(A) and increased the number of action
      potentials. The responses were associated with the decreases in the resting
      membrane potential (RMP) and duration of depolarization phase of action potential
      (DDP). The application of 2 mM tetraethylammonium (TEA, an I(K) blocker) produced
      a 55 % inhibition of I(K). Irrespective of the presence of both I(D) and I(A)
      blockers, the I(K) was the predominant K+ current. The prolongation of duration
      of action potential was usually observed following TEA treatment, suggesting that
      I(A) and I(K) had independent effects regulating the intrinsic firing properties
      of the action potential number and timing, respectively. Furthermore, the
      response characteristics of action potentials in the presence of both 4-AP and
      TEA resemble those of TG neurons in rats following chronic constriction nerve
      injury of the infraorbital nerve as well as after inferior alveolar nerve
      section. Thus, reducing effects of both I(A) and I(K) may be useful to
      investigate the mechanism of allodynia.

PMID- 20030624
TI  - EGFR-targeted therapy in malignant glioma: novel aspects and mechanisms of drug
      resistance.
AB  - Glioblastoma, GBM, is the most frequent brain malignancy in adults. Patients with
      these tumors survive only, approximately, one year after diagnosis and rarely
      survive beyond two years. This poor prognosis is, in part, due to our
      insufficient understanding of the complex aggressive nature of these tumors and
      the lack of effective therapy. In GBM, over-expression of EGFR and/or its
      constitutively activated variant EGFRvIII is a major characteristic and is
      associated with tumorigenesis and more aggressive phenotypes, such as,
      invasiveness and therapeutic resistance. Consequently, both have been major
      targets for GBM therapy, however, clinical trials of EGFR- and EGFRvIII-targeted
      therapies have yielded unsatisfactory results and the molecular basis for the
      poor results is still unclear. Thus, in this review, we will summarize results of
      recent clinical trials and recent advances made in the understanding of the
      EGFR/EGFRvIII pathways with a key focus on those associated with intrinsic
      resistance of GBM to EGFR-targeted therapy. For example, emerging evidence
      indicates an important role that PTEN plays in predicting GBM response to EGFR
      targeted therapy. Aberrant Akt/mTOR pathway has been shown to contribute to the
      resistant phenotype. Also, several studies have reported that EGFR/EGFRvIII's
      cross-talk with the oncogenic transcription factorSTAT3 and receptor tyrosine
      kinases, (c-Met and PDGFR) potentially lead to GBM resistance to anti-EGFR
      therapy. Other emerging mechanisms, including one involving HMG-CoA reductase,
      will also be discussed in this mini-review. These recent findings have provided
      new insight into the highly complex and interactive nature of the EGFR pathway
      and generated rationales for novel combinational targeted therapies for these
      tumors.

PMID- 20030629
TI  - Increased hepatic and decreased urinary metallothionein in rats after cessation
      of oral cadmium exposure.
AB  - We investigated the role of metallothionein (MT) in tissues after cessation of
      cadmium (Cd) exposure. Wistar rats of both genders were given CdCl(2) in drinking
      water at daily doses of 0, 2.5, 5.0 or 10.0 mg Cd/kg body-weight for 12 weeks.
      Half of the animals were then killed; the others were given Cd-free water for the
      following 16 weeks, i.e. until 28 weeks after start of the experiment (28-week
      rats). We observed dose-dependent increases in the levels of MT in the tissues of
      rats 12 weeks after beginning the experiment (12-week rats). After the exposure
      ceased, levels of MT in the 28-week rats changed in three ways: an increase in
      the liver, persistence in the kidney cortex and a decrease in the medulla,
      relative to those levels in their 12-week counterparts. Biomarkers of kidney
      dysfunction were determined to be urinary MT (UMT) and urinary N-acetyl-beta-D
      glucosaminidase (UNAG). After 12 weeks, we observed dose-related statistically
      significant increases in UMT and UNAG in all of the Cd-exposed groups. A
      statistically significant decrease for UNAG between the 12- and 28-week rats
      occurred among males at the lowest Cd dose and for UMT in all of the Cd-exposed
      groups. The unchanged tissue levels of MT in the kidney cortex suggest that
      decreased UMT is a sign either of (i) decreased transport of Cd-MT from the liver
      via blood plasma to the renal tubules or (ii) increased tubular reabsorption and
      recovery of renal tubular function.

PMID- 20030628
TI  - Molecular mechanism of elongation factor 1A inhibition by a Legionella
      pneumophila glycosyltransferase.
AB  - Legionnaires' disease is caused by a lethal colonization of alveolar macrophages
      with the Gram-negative bacterium Legionella pneumophila. LpGT (L. pneumophila
      glucosyltransferase; also known as Lgt1) has recently been identified as a
      virulence factor, shutting down protein synthesis in the human cell by specific
      glucosylation of EF1A (elongation factor 1A), using an unknown mode of substrate
      recognition and a retaining mechanism for glycosyl transfer. We have determined
      the crystal structure of LpGT in complex with substrates, revealing a GT-A fold
      with two unusual protruding domains. Through structure-guided mutagenesis of
      LpGT, several residues essential for binding of the UDP-glucose-donor and EF1A
      acceptor substrates were identified, which also affected L. pneumophila virulence
      as demonstrated by microinjection studies. Together, these results suggested that
      a positively charged EF1A loop binds to a negatively charged conserved groove on
      the LpGT structure, and that two asparagine residues are essential for catalysis.
      Furthermore, we showed that two further L. pneumophila glycosyltransferases
      possessed the conserved UDP-glucose-binding sites and EF1A-binding grooves, and
      are, like LpGT, translocated into the macrophage through the Icm/Dot
      (intracellular multiplication/defect in organelle trafficking) system.

PMID- 20030630
TI  - Modelling of drug disposition kinetics in in vitro intestinal absorption cell
      models.
AB  - One major prerequisite for an orally administered drug is the ability to cross
      the intestinal epithelia from intestinal lumen into the blood circulation.
      Therefore, the absorption potential of molecules is studied early on during the
      drug development process. Permeation experiments using cultured cell monolayers
      are one of the most often applied methods to screen and also to predict in more
      detail the intestinal absorption potential of molecules in preclinical phase.
      Furthermore, these studies are also used to screen the molecules for transporter
      interactions as well as for more detailed mechanistic studies of the transfer
      routes involved. Several mathematical and computational models with complexity
      varying from simple non-mechanistic single barrier models to mechanistically more
      detailed compartmental models have been developed to describe the drug
      disposition during these in vitro permeation experiments. This MiniReview gives
      an overview of these models and their applications. Also the implications of
      these models to the prediction of intestinal absorption in vivo are discussed.

PMID- 20030631
TI  - Calcium-sensing receptors induce apoptosis in rat cardiomyocytes via the
      endo(sarco)plasmic reticulum pathway during hypoxia/reoxygenation.
AB  - The calcium-sensing receptor (CaR) is a G protein-coupled receptor. The CaR
      stimulation elicits phospholipase C-mediated inositol triphosphate formation,
      leading to an elevation in the level of intracellular calcium released from
      endoplasmic reticulum (ER). Depletion of ER Ca(2+) leads to ER stress, which is
      thought to induce apoptosis. Intracellular calcium overload-induced apoptosis in
      cardiac myocytes during hypoxia-reoxygenation (H/Re) has been demonstrated.
      However, the links between CaR, ER stress and apoptosis during H/Re are unclear.
      This study hypothesized that the CaR could induce apoptosis in neonatal rat
      cardiomyocytes during H/Re via the ER stress pathway. Neonatal rat cardiomyocytes
      were subjected to 3 hr of hypoxia, followed by 6 hr of reoxygenation. CaR
      expression was elevated and the number of apoptotic cells was significantly
      increased, as shown by transferase-mediated dUTP nick end-labelling, with
      exposure to CaCl(2), a CaR activator, during H/Re. The intracellular calcium
      concentration was significantly elevated and the Ca(2+) concentration in the ER
      was dramatically decreased during H/Re with CaCl(2); both intracellular and ER
      calcium concentrations were detected by laser confocal microscopy. Expression of
      GRP78 (glucose-regulated protein 78), the cleavage products of ATF6 (activating
      transcription factor 6), phospho-PERK [pancreatic ER kinase (PKR)-like ER
      kinase], the activated fragments of caspase-12, and phospho-JNK (c-Jun NH(2)
      terminal kinase) were increased following exposure to CaCl(2) during H/Re. Our
      results confirmed that the activated CaR can induce cardiomyocyte apoptosis via
      ER stress-associated apoptotic pathways during H/Re.

PMID- 20030632
TI  - Formalin-induced short- and long-term modulation of Cav currents expressed in
      Xenopus oocytes: an in vitro cellular model for formalin-induced pain.
AB  - Xenopus oocytes expressing high voltage-gated calcium channels (Ca(v)) were
      exposed to formalin (0.5%, v/v, 5 min.) and the oocyte death and Ca(v) currents
      were studied for up to 10 days. Ca(v) channels were expressed with
      alpha(1)beta(1)b and alpha(2)delta sub-units and the currents (I(Ba)) were
      studied by voltage clamp. None of the oocytes was dead during the exposure to
      formalin. Oocyte death was significant between day 1 and day 5 after the exposure
      to formalin and was uniform among the oocytes expressing various Ca(v) channels.
      Peak I(Ba) of all Ca(v) and A(1), the inactivating current component was
      decreased whereas the non-inactivated R current was not affected by 5 min.
      exposure to formalin. On day 1 after the exposure to formalin, Ca(v)1.2c currents
      were increased, 2.1 and 2.2 currents were decreased and 2.3 currents were
      unaltered. On day 5, both peak I(Ba) and A(1) currents were increased. Ca(v)1.2c,
      2.2 and 2.3 currents were increased and Ca(v)2.1 was unaltered on day 10 after
      the exposure to formalin. Protein kinase C (PKC) may be involved in formalin
      induced increase in Ca(v) currents due to the (i) requirement for Ca(v)beta(1)b
      sub-units; (ii) decreased phorbol-12-myristate,13-acetate potentiation of
      Ca(v)2.3 currents; (iii) absence of potentiation of Ca(v)2.3 currents following
      down-regulation of PKC; and (iv) absence of potentiation of Ca(v)2.2 or 2.3
      currents with Ser-->Ala mutation of Ca(v)alpha(1)2.2 or 2.3 sub-units. Increased
      Ca(v) currents and PKC activation may coincide with changes observed in in vivo
      pain investigations, and oocytes incubated with formalin may serve as an in vitro
      model for some cellular mechanisms of pain.

PMID- 20030633
TI  - Mode of action considerations in the quantitative assessment of tumour responses
      in the liver.
AB  - Chemical carcinogenesis is a complex, multi-stage process and the relationship
      between dose and tumour formation is an important consideration in the risk
      assessment of chemicals. Extrapolation from empirical dose-response relationships
      obtained in experimental studies has been criticized, as it fails to take into
      account information on mode of action. Strategies for incorporating mode of
      action information into the risk assessment of chemical carcinogens are
      described, with a focus on hepatic cancer. Either toxicokinetic or toxicodynamic
      processes can be addressed. Whilst the former have been the focus of more
      attention to date, for example by using physiologically based modelling, there is
      increasing interest in the development of mode of action-based toxicodynamic
      models. These have the advantage that they do not require extreme assumptions,
      and may be amenable to paramaterization using human data. This is rarely if ever
      possible when using conventional dose-tumour response relationships. The
      approaches discussed are illustrated using chloroform as a case study. This
      compound is converted to a cytotoxic metabolite, phosgene, by CYP2E1 in liver
      and/or kidney. Cytotoxicity results in proliferative regeneration, with increased
      probability of tumour formation. Both physiologically based toxicokinetic and
      toxicodynamic models have been developed, and it is possible to use probabilistic
      approaches incorporating, for example, data on the distribution of hepatic CYP2E1
      levels. Mode of action can provide an invaluable link between observable,
      experimental data, on both toxicokinetics and toxicodynamics, and chemical
      specific risk assessment, based on physiological approaches.

PMID- 20030634
TI  - Biopharmaceutical classification based on solubility and dissolution: a
      reappraisal of criteria for hypothesis models in the light of the experimental
      observations.
AB  - The diffusion layer model of drug dissolution is used for the simulation of oral
      drug absorption as well as for the analysis of experimental data. The governing
      role of saturation solubility in the rate of dissolution makes this parameter
      predominant for biopharmaceutical classification purposes. The hypothesis models
      and criteria associated with the use of solubility and dissolution for the
      biopharmaceutical classification of compounds and marketed drugs are reviewed in
      this article. The complex hydrodynamics in the in vitro dissolution apparatuses
      as well as the motility in the gastrointestinal tract do not allow the
      application of the diffusion layer model in these systems, as this has been built
      and verified in the rotating disk device. The solubilizing capacity of
      gastrointestinal fluids media is higher than the aqueous saturation solubility
      usually reported and used for biopharmaceutical purposes. Emphasis is given on
      the reaction-limited model of dissolution which provides a useful alternative not
      based on diffusion principles. Model independent dissolution parameters are more
      useful for regulators as our knowledge for the dissolution mechanism(s) under in
      vivo conditions is limited.

PMID- 20030635
TI  - The TRAF1/C5 locus confers risk for familial and severe alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is a common hair loss disorder with a complex
      mode of inheritance. Autoimmune mechanisms are presumed to be crucial
      aetiologically. It is plausible that a number of autoimmune disorders may share a
      common genetic background. This phenomenon has been demonstrated in previous
      studies, which have shown an overlap of susceptibility alleles between AA and
      other autoimmune disorders. Recent studies have shown that genetic variants on
      the TRAF1/C5 (tumor necrosis factor receptor-associated factor 1, complement
      component 5) locus confer susceptibility to rheumatoid arthritis (RA).
      OBJECTIVES: To examine the role of the TRAF1/C5 locus in the development of AA
      using a large sample of 1,195 patients with AA and 1280 controls. METHODS: We
      genotyped the two most significant single nucleotide polymorphisms (SNPs)
      (rs10818488, rs2416808) from a former RA candidate gene study. After having
      obtained evidence for association, we performed a fine-mapping study and
      genotyped the locus with an additional 27 SNPs. RESULTS: While no significant
      result was obtained for the overall sample, rs2416808 showed significant
      associations in the analysis of the subgroups with severe AA and with a positive
      family history. The most significant P-value for rs2416808 was in familial cases
      (P = 0.004, P(corr) = 0.026). The fine mapping revealed significant associations
      for four additional SNPs in the analysis of subgroups, with rs2416808 remaining
      the most significant marker. CONCLUSIONS: Our results point to the involvement of
      the TRAF1/C5 locus in the aetiology of familial and severe AA, and provide
      further support for a shared aetiology between AA and other autoimmune disorders.

PMID- 20030636
TI  - Vitamin D in treated melanoma patients on follow up.

PMID- 20030637
TI  - Ethnic differences in pain, itch and thermal detection in response to topical
      capsaicin: African Americans display a notably limited hyperalgesia and
      neurogenic inflammation.
AB  - BACKGROUND: Topical application of capsaicin commonly produces burning, stinging
      and itching as well as hyperalgesia to heat stimuli via activation of transient
      receptor potential vanilloid subtype 1. OBJECTIVES: To investigate whether there
      are differences in sensory response and neurogenic inflammation to topical
      capsaicin in four different ethnic populations with different skin types.
      METHODS: The study was performed in 40 healthy subjects consisting of 10 African
      Americans, 10 East Asians, 10 Hispanics and 10 Caucasians. Warmth sensation and
      heat pain detection thresholds, as well as pain intensity, were measured before
      and after application of capsaicin or placebo on forearms along with skin blood
      flow and the extent of the flare reaction. RESULTS: In African Americans the heat
      pain detection threshold, pain intensity and skin blood flow did not change
      significantly after capsaicin application, while in the other three ethnic groups
      a significant change occurred characterized by hyperalgesia and vasodilatation.
      The postcapsaicin warmth sensation threshold increased in African Americans and
      decreased in Hispanics, the latter also uniquely experiencing postcapsaicin itch.
      CONCLUSIONS: Our observations indicate that African Americans display a limited
      hypersensitivity following topical capsaicin, compared with the three other
      ethnic groups.

PMID- 20030638
TI  - Differential gene expression in drug hypersensitivity reactions: induction of
      alarmins in severe bullous diseases.
AB  - BACKGROUND: Delayed hypersensitivity reactions to drugs can be life-threatening
      and constitute a growing problem in clinical practice. Although drug-specific T
      cells seem to be involved, the cellular and molecular bases of their
      aetiopathology are not fully understood. OBJECTIVES: To study the molecular
      mechanisms underlying the pathogenesis and the clinical heterogeneity of
      cutaneous delayed hypersensitivity reactions to drugs. MATERIALS AND METHODS: We
      characterized the gene expression profiles of peripheral blood mononuclear cells
      (PBMCs) isolated from patients during the acute phase of the reaction and upon
      resolution of clinical symptoms using a cDNA array technology. Low-density arrays
      were used to confirm differential expression of selected genes during the acute
      disease in patients and to compare gene expression in patients and exposed
      control donors by quantitative real-time polymerase chain reaction. RESULTS:
      Eighty-five genes were found to be differentially expressed during the acute
      phase of cutaneous drug-induced delayed hypersensitivity reactions. Furthermore,
      92 genes with distinct expression patterns in severe and benign diseases during
      the acute phase were identified. PBMCs from patients with severe bullous diseases
      showed a characteristic gene expression pattern with lower expression of genes
      encoding T cell-specific proteins and high expression of cell cycle-related genes
      and genes coding for inflammatory-related mediators among which several
      endogenous damage-associated molecular patterns (DAMPs) or alarmins were found.
      CONCLUSIONS: Distinct gene expression profiles in PMBCs define benign and severe
      clinical entities. Overexpression of endogenous DAMPs in Stevens-Johnson syndrome
      and toxic epidermal necrolysis suggest that drugs can trigger the alarmin system
      in sensitized patients leading to life-threatening diseases.

PMID- 20030639
TI  - Keratin mutations in patients with epidermolysis bullosa simplex: correlations
      between phenotype severity and disturbance of intermediate filament molecular
      structure.
AB  - BACKGROUND: Epidermolysis bullosa simplex (EBS) is an inherited skin disorder
      caused by mutations in the keratin 5 (KRT5) and keratin 14 (KRT14) genes, with
      fragility of basal keratinocytes leading to epidermal cytolysis and blistering.
      OBJECTIVES: In this study, we characterized mutations in KRT5 and KRT14 genes in
      patients with EBS and investigated their possible structure-function
      correlations. MATERIALS AND METHODS: Mutations were characterized using
      polymerase chain reaction (PCR) and DNA sequencing. Further, to explore possible
      correlations with function, the structural effects of the mutations in segment 2B
      of KRT5 and KRT14 and associated with EBS in our patients, as well as those
      reported previously, were modelled by molecular dynamics with the aid of the
      known crystal structure of the analogous segment of human vimentin. RESULTS: We
      have identified mutations in the KRT5 and KRT14 genes in 16 of 23 families
      affected by EBS in the Czech Republic. Eleven different sequence variants were
      found, of which four have not been reported previously. Novel mutations were
      found in two patients with the EBS-Dowling-Meara variant (EBS-DM) [KRT14
      p.Ser128Pro and KRT14-p.Gln374_Leu387dup(14)] and in three patients with
      localized EBS (KRT14-p.Leu136Pro and KRT5-p.Val143Ala). Molecular dynamics
      studies show that the mutations p.Glu411del and p.Ile467Thr perturb the secondary
      alpha-helical structure of the mutated polypeptide chain, the deletion
      p.Glu411del in KRT14 has a strong but only local influence on the secondary
      structure of KRT14, and the structural impact of the mutation p.Ile467Thr in KRT5
      is spread along the helix to the C-terminus. In all the other point mutations
      studied, the direct structural impact was significantly weaker and did not
      destroy the alpha-helical pattern of the secondary protein structure. The changes
      of 3-D structure of the KRT5/KRT14 dimer induced by the steric structural impact
      of the single point mutations, and the resulting altered inter- and
      intramolecular contacts, are spread along the protein helices to the protein C
      terminus, but the overall alpha-helical character of the secondary structure is
      not destroyed and the atomic displacements induced by mutations cause only
      limited-scale changes of the quaternary structure of the dimer. CONCLUSIONS: The
      results of molecular modelling show relationships between patients' phenotypes
      and the structural effects of individual mutations.

PMID- 20030640
TI  - Complete remission in a patient with multifocal metastatic cutaneous angiosarcoma
      with a combination of paclitaxel and sorafenib.

PMID- 20030641
TI  - Histological regression in primary melanoma: not a predictor of sentinel lymph
      node metastasis in a cohort of 397 patients.
AB  - BACKGROUND: Regression has been proposed as a potential marker of dissemination
      in thin melanomas. Previous studies have shown conflicting results. OBJECTIVE: To
      determine if regression in melanoma is associated with an increased risk of
      sentinel lymph node (SLN) metastasis. METHODS: A cohort analysis was conducted.
      Data on all patients were collected on a standardized case report form during 10
      years. A total of 397 consecutive patients with melanoma who underwent a SLN
      biopsy were analysed. All cases of melanoma and SLN biopsies were examined by the
      same two pathologists. Differences between melanomas with and without SLN
      metastasis were compared using Fisher's exact test or the two-sample t-test and
      the chi(2) test. Multivariable logistic regression was used to adjust for
      possible confounding factors. RESULTS: We analysed 397 patients (411 melanomas)
      who underwent a SLN biopsy. The median Breslow index was 1.8 mm (interquartile
      range 1.1-3). Regression was observed in 23% (n = 94). SLN metastases were
      observed in 26% (n = 106). The frequency of SLN metastasis was 16% in melanomas
      with regression and 29% without regression (P = 0.012). The adjusted odds ratio
      (OR) for regressive melanoma was 0.9 [95% confidence interval (CI) 0.4-1.9; P =
      0.777]. The risk of SLN metastasis was increased in melanoma cases with a Breslow
      index from 1.5 to < 2.0 mm (adjusted OR 3.1; 95% CI 1.4-7.1; P = 0.006) and >or=
      2.0 mm (adjusted OR 3.5; 95% CI 1.7-7.4; P = 0.001) and ulceration of the
      melanoma (adjusted OR 1.8; 95% CI 1.1-3.2; P = 0.03). CONCLUSION: Regression is
      not an independent predictor of the risk of SLN metastasis in melanoma.

PMID- 20030642
TI  - Iontophoretic terbinafine delivery in onychomycosis: questionable nail growth.

PMID- 20030643
TI  - Follicular hyperkeratosis as a manifestation of Sezary syndrome.

PMID- 20030645
TI  - The role of radiation therapy in locally advanced breast cancer.
AB  - The purpose of the study was to evaluate and compare the impact of postoperative
      radiotherapy, whether it was based on the clinical stage at presentation of the
      disease or on the pathological downstaged disease after initial chemotherapy for
      non-inflammatory locally advanced breast cancer (LABC). We retrospectively
      analyzed locoregional recurrence (LRR), relapse free survival (RFS), overall
      survival (OS) and disease free survival (DFS) in 55 patients treated for non
      inflammatory LABC with neoadjuvant chemotherapy and surgery with or without
      radiotherapy. The mean follow-up was 55 months. The 3-year OS was 74%, DFS 73%
      and RFS 87%. The OS and DFS benefit was seen in those receiving radiation, with a
      mean OS of 89 months versus 68 months (p = 0.029) and mean DFS of 72 months
      versus 54 months (p = 0.029). Total LRR was 11% (8% versus 17% in the non
      radiotherapy group, p = 0.349) and mean RFS of 95 months versus 86 months (p =
      0.164). If the treatment planning was to be based on the original extent of the
      disease, then all patients in our study should have received adjuvant
      radiotherapy. Significantly lower OS and DFS without the addition of radiotherapy
      suggests that indication for radiation treatment should be based on the clinical
      pre-chemotherapy stage rather than the pathological post-chemotherapy stage.
      Radiation should therefore always be considered regardless of the response to
      initial chemotherapy for non-inflammatory LABC.

PMID- 20030644
TI  - Expression of KIT receptor tyrosine kinase in endothelial cells of juvenile brain
      tumors.
AB  - KIT receptor tyrosine kinase is expressed in tumor endothelial cells of adult
      glioblastomas, but its expression in pediatric brain tumor endothelial cells is
      unknown. We assessed expression of KIT, phosphorylated KIT, stem cell factor
      (SCF) and vascular endothelial growth factor receptor-2 (VEGFR-2) in 35 juvenile
      pilocytic astrocytomas and 49 other pediatric brain tumors using
      immunohistochemistry, and KIT messenger RNA (mRNA) using in situ hybridization.
      KIT and phospho-KIT were moderately or strongly expressed in tumor endothelia of
      37% and 35% of pilocytic astrocytomas, respectively, whereas marked SCF and VEGFR
      2 expression was uncommon. KIT mRNA was detected in tumor endothelial cells.
      Tumor endothelial cell KIT expression was strongly (P < 0.01) associated with
      endothelial cell phospho-KIT and SCF expression, and with tumor KIT (P = 0.0011)
      and VEGFR-2 expression (P = 0.022). KIT and phospho-KIT were present in
      endothelia of other pediatric brain tumors, notably ependymomas. Endothelial cell
      KIT expression was associated with a young age at diagnosis of pilocytic
      astrocytoma or ependymoma, and it was occasionally present in histologically
      normal tissue of the fetus and children. We conclude that KIT is commonly present
      in endothelial cells of juvenile brain tumors and thus may play a role in
      angiogenesis in these neoplasms.

PMID- 20030646
TI  - Hydatid disease of the breast.

PMID- 20030647
TI  - Racial differences in adjuvant systemic therapy for early breast cancer among
      Medicaid beneficiaries.
AB  - Black breast cancer patients have shorter survival compared to whites. Lack of
      optimal treatment may be a potential explanation for this difference. Although
      racial disparities in surgical and radiation therapy have been studied
      extensively, there is little information on racial disparities in use of adjuvant
      systemic therapy. Medicaid enrolled patients provide an opportunity to examine
      racial disparity in breast cancer treatment by minimizing the roles of access to
      health care and socioeconomic status. This study, therefore, compared breast
      cancer treatment, particularly adjuvant systemic therapy and survival in black
      and white women enrolled in Medicaid. Linked New Jersey Cancer Registry and
      Medicaid Research files provided diagnostic, prognostic, and treatment
      information on 237 black and 485 white women aged 20-64 years diagnosed with
      early stage breast cancer between January 1997 and December 2001. Racial
      differences in treatment and survival were examined using logistic regression and
      Cox proportional hazards models respectively. There were no differences in
      surgical, radiation, or adjuvant systemic treatment between blacks and whites.
      Breast cancer specific mortality (Hazard ratio (HR) = 1.37; 95% confidence
      interval (CI) = 0.94-1.98) and all-cause mortality (HR = 1.43; 95% CI = 1.08
      1.89) were higher among blacks than whites. In this study of Medicaid-enrolled
      women with similar socioeconomic status and health care access, blacks and whites
      received similar breast cancer treatment. In spite of this, blacks had higher
      mortality than whites. Our findings suggest that factors other than treatment
      differences may contribute to the racial disparity in mortality.

PMID- 20030648
TI  - Adenoid cystic carcinoma of the breast: a review of a single institution's
      experience.

PMID- 20030649
TI  - Does compliance with radiation therapy differ in African-American patients with
      early-stage breast cancer?
AB  - The worse outcomes in African-American (AA) breast cancer patients have been
      attributed to a variety of factors, including compliance/variations with
      treatment. We evaluated a large cohort of AA patients treated with breast
      conservation therapy (BCT) in an effort to determine if compliance with radiation
      or if choice of chemotherapy regimen could be a contributing factor for the worse
      outcomes reported in AA patients. Our two cohorts consisted of 221 AA and 2170
      white patients treated with BCT. Chart reviews were conducted to document dates
      of treatment, treatment breaks, dose delivered, and chemotherapy delivered. The
      data were analyzed to detect differences between the two cohorts. The median
      radiation dose delivered (including cone-down) was 64 Gy in both cohorts (p =
      0.9910). The median number of treatment days was: AA, 45 (range 21-71 days)
      versus white, 45 (range 14-90 days; p = 0.8465). The chemotherapy regimens
      administered were: adriamycin/cytoxan (17% AA versus 19% white, respectively),
      adriamycin/cytoxan/taxol (13% versus 5%), cytoxan/methotrexate/5-FU (53% versus
      59%), cytoxan/methotrexate/5-FU/vincristine (0% versus 3%), cytoxan/adriamycin/5
      FU (12% versus 11%), high dose/transplant (0% versus 1%), and other (4% versus
      5%), p = 0.113. Our large institutional series suggests that compliance with
      radiation therapy, once patients are seen in consultation and simulated, does not
      differ significantly between AA and white patients. In our large cancer center
      environment, AA patients referred for radiation therapy appear to receive the
      same radiation doses in a comparable time frame to white patients. Further
      exploration of compliance for adjuvant chemotherapy regimens in AA patients is
      warranted.

PMID- 20030650
TI  - Comparing the effect of diclofenac gel and piroxicam gel on mastalgia.

PMID- 20030651
TI  - Imaging features of bilateral lupus mastitis.

PMID- 20030652
TI  - Granulomatous mastitis: clinical, pathological features, and management.
AB  - This clinical study was conducted to present clinical, radiologic, and
      histopathologic features of Granulomatous Mastitis (GM) and evaluate the result
      of surgical and steroid treatment. Sixteen cases diagnosed histologically as GM
      were reviewed. Patient characteristics, clinical presentation, radiologic
      imaging, microbiologic, histopathologic assessment, treatment modalities,
      recurrence, morbidity, and follow-up data were analyzed. Majority of the patients
      were child bearing age and all of the patients had a history of breast feeding.
      Radiologic findings were nonspecific. Histopathology showed the characteristic
      distribution of granulomatous inflammation in all cases. In 12 cases, surgical
      excision of the lesion with negative margins was performed. Four cases required
      quadranectomy because of wideness of the disease. Three patients who had local
      reoccurrence and three resistant patients were treated by oral prednisone after
      surgical attempt. Complete remission was obtained and no further recurrence was
      observed in this patients. GM predominantly occurs in premenopausal women and the
      clinical symptoms might be misjudged as breast cancer. Histopathologic
      examination remains the gold standard for the diagnosis. Wide excision of the
      lesions is the recommended therapy and we suggest steroid therapy in resistant or
      recurrent disease following the idea that the disease has an autoimmune
      component.

PMID- 20030653
TI  - An exception to tumour neoangiogenesis in a malignant breast-lesion.
AB  - Magnetic resonance-mammography is regarded as the most sensitive diagnostic
      modality in the detection of breast cancer. It uses the tumour neoangiogenesis to
      depict lesions after intravenous contrast agent injection. It is said, that for
      tumours exceeding a diameter of three millimetres contrast agent enhancement is
      mandatory. In our case report we describe a rare tumour growth condition. We
      observed a large invasive carcinoma (18 millimetres diameter) without contrast
      enhancement in breast MRI due to an almost missing tumour neoangiogenesis. The
      cancer had a low cellularity and a strong desmoplastic reaction.

PMID- 20030654
TI  - Assessing the knowledge and attitudes regarding genetic testing for breast cancer
      risk in our region of southeastern Georgia.
AB  - Genetic testing for the breast cancer susceptibility genes, BRCA1 and BRCA2, has
      been available for over a decade. Positive test results carry significant
      medical, psychological, and social implications. Knowledge of the public's
      awareness concerning BRCA testing, and perceived benefits and barriers to testing
      can help refine educational programs and identify subgroups needing additional
      support. Patients and their acquaintances with a breast complaint attending a
      surgical clinic or private office were asked to complete a questionnaire about
      their knowledge of breast cancer genes and their desire to be tested. Demographic
      information collected included ethnicity, education background, age, income, and
      personal and family history of breast cancer, knowledge of BRCA genes and
      testing, and their willingness to participate in genetic counseling. A total of
      222 people completed the questionnaire that showed the majority of subjects in
      southeast Georgia believe breast cancer is inherited 26-50% of the time.
      Caucasians and those with advanced degrees are the most informed regarding
      awareness of BRCA genes (p < 0.05); the least informed groups include African
      Americans and those with no more than a college education. Participants with a
      family history of breast cancer were significantly more likely to know that genes
      had been identified that indicate an increased risk of breast cancer (p < 0.05).
      A history of breast cancer did not impact the degree of awareness (p > 0.05).
      Subjects aware of genetic testing are more willing to utilize counseling (p <
      0.05). Perceptions of breast cancer inheritance, awareness of susceptibility
      genes, and availability of testing and counseling are not uniform among all
      population subgroups. In southeast Georgia, educational efforts should focus on
      the less educated and minority groups.

PMID- 20030655
TI  - True recurrences and new primary tumors have different clinical features in
      invasive breast cancer patients with ipsilateral breast tumor relapse after
      breast-conserving treatment.
AB  - Ipsilateral breast tumor relapse (IBTR) after breast-conserving treatment (BCT)
      may represent two distinct types of lesion, including a true recurrence (TR) or a
      new primary tumor (NPT). The aim of this study was to ascertain the difference
      between TRs and NPTs and to show the clinical significance of classifying IBTR
      into these two types of recurrence. Patients (n = 2,075) with unilateral invasive
      breast cancer who underwent BCT between 1987 and 2005 at Saitama Cancer Center
      were analyzed. IBTR was classified into TR and NPT, which was based on all
      clinical and pathological features of both a primary tumor and IBTR that can be
      evaluated. IBTR-free survival and the risk factors were analyzed in order to
      compare the findings for TR and NPT. In addition, the salvage surgical methods
      for IBTR and overall survival after IBTR were analyzed. Sixty patients with IBTR
      were classified into 52 with TR and eight with NPT. IBTR-free survival was
      significantly shorter in the patients with TR than those with NPT. Young age,
      tumor size, a positive surgical margin, and omission of radiation therapy (RT)
      were significant risk factors for TR. Omission of RT was the only significant
      risk factor for NPT. In 27 patients who underwent a repeat lumpectomy for TR,
      four had a second IBTR. The overall survival after IBTR was worse in patients
      with TR than NPT. TR and NPT show quite different clinical features. Classifying
      IBTR into TR or NPT can therefore help to select the most appropriate treatment
      for IBTR.

PMID- 20030656
TI  - Axillary Metastatic Disease Secondary to Occult Breast Cancer: A Diagnostic and
      Therapeutic Dilemma.

PMID- 20030657
TI  - Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd
      Ed. with the Bayley Scales of Infant Development II in a low-risk sample.
AB  - Abstract Background This study assessed the concurrent validity of the Ages and
      Stages Questionnaire (ASQ) compared with Bayley Scales of Infant Development II
      (BSID II) amongst children aged 24 months. Methods Data were collected from 53
      infants and mothers who participated in the New York State Angler Cohort Child
      Development Study. Parents completed the 24-month ASQ to assess communication,
      personal-social, problem-solving ability, and fine and gross motor control. The
      BSID II was administered by a clinical psychologist at the 24-month home visit
      for cognitive and psychomotor assessment. The ASQ was scored using age-specific
      norms of <2 SDs below any domain mean to define failure. A BSID II score of <85
      indicated mild or severe delay, while a score of <70 suggested a severe delay.
      Results Scores on the ASQ communication and personal-social domains were
      moderately correlated with the BSID II Mental Scale (R= 0.52, P < 0.001; R= 0.45,
      P < 0.01) and ASQ gross motor with the BSID II Motor Scale (R= 0.46, P < 0.01),
      whereas ASQ problem-solving and fine motor domains were not significantly
      correlated with BSID II scores. The ASQ had a sensitivity of 100% and specificity
      of 87% at 24 months (n= 40) for severely delayed status. Conclusions Results
      suggest the ASQs provide a simple, valid, and cost-effective method for
      clinicians and field-based researchers to reduce the number of standardized
      assessments required to identify developmentally delayed infants at age 24
      months. Future studies should further assess the validity of the ASQs in larger,
      more diverse populations of infants.

PMID- 20030658
TI  - Legal dilemmas for clinicians involved in the care and treatment of children and
      young people with mental disorder.
AB  - BACKGROUND: The 2008 revised Mental Health Act Code of Practice describes the
      legal framework governing the admission to hospital and treatment of children and
      young people for mental disorders as complex. Clinicians are required to be
      conversant with common law principles as well as the Mental Health Act (MHA),
      Children Act, Mental Capacity Act (MCA), Family Law Reform Act, Human Rights Act,
      and the United Nations Convention on the Rights of the Child. Professionals
      working with the MHA and the MCA have a legal duty to have regard to the
      respective Codes of Practice (MHA Code and MCA Code). In addition there is a need
      to keep up-to-date with developments in case law. The recent guidance from the
      National Institute for Mental Health in England, 'The Legal Aspects of the Care
      and Treatment of Children and Young People with Mental Disorder' draws all of the
      legal regimes together and suggests pointers on the most appropriate course of
      action when the regimes overlap. DISCUSSION: This paper will aim to highlight
      legal dilemmas relating to the care and treatment of under 18-year-olds for
      mental disorder and to discuss the impact of these on clinical practice. The new
      legal framework will be discussed with reference to hypothetical cases. Key
      issues include age and maturity, capacity, deprivation of liberty and the zone of
      parental control (ZPC). CONCLUSIONS: It is essential that clinicians are aware of
      their responsibilities within the new legal framework in order to avoid becoming
      a target for litigation. This paper is aimed at meeting the recommendation for
      clinicians to be aware of their responsibilities and engage in appropriate
      training.

PMID- 20030659
TI  - Goal-setting in paediatric rehabilitation: perceptions of parents and
      professional.
AB  - BACKGROUND: In paediatric rehabilitation, there is a belief in goal-setting as a
      fundamental component of decision-making that encourages collaboration and
      motivation, and improves outcomes. This study aimed to explore parents' and
      professionals' perceptions of setting and implementing goals within a family
      centred rehabilitation programme for preschoolers with cerebral palsy (CP).
      METHODS: Parents and service providers of 13 preschoolers with CP, classified in
      Gross Motor Function Classification System level I-III, participated in two-step
      focus group interviews. RESULTS: Three major themes emerged, each with two
      subthemes: (1) 'Goals enhance competence' with the subthemes 'parents as
      drivers', and 'awareness through observation'; (2) 'Goals direct attention' with
      the subthemes 'goals as valuable means' and 'collaboration through
      participation', and (3) 'Goals enter everyday life' with the subthemes 'goals as
      activities' and 'training vs. everyday practise'. A fourth theme 'child
      perspective' with the subthemes 'follow-up initiative', 'capture mastery', and
      'create learning opportunities' was both an exclusive theme and integrated in the
      other three main themes. CONCLUSIONS: Active involvement of parents throughout
      the process of setting and implementing goals seemed to increase their feeling of
      competency and partnership with professionals. Concrete goals based on families'
      preferences and concerns, participatory observation, and discussions with
      professionals, came out as valuable means for practice of functional tasks within
      home environments.

PMID- 20030660
TI  - Is there a relationship between foetal position and both preferred lying posture
      after birth and pattern of subsequent postural deformity in non-ambulant people
      with cerebral palsy?
AB  - BACKGROUND: A pattern of postural deformity was observed in a previous study that
      included an association between direction of spinal curvature and direction of
      windsweeping with more windswept deformities occurring to the right and lateral
      spinal curvatures occurring convex to the left. The direction of this pattern was
      found to be associated with preferred lying posture in early life. The aim of
      this study was to test the association between foetal position and both the
      preferred lying posture after birth, and the direction of subsequent postural
      deformity in non-ambulant children with cerebral palsy (CP). METHODS: A
      retrospective cohort study was carried out involving 60 participants at level
      five on the gross motor function classification for CP. Foetal position during
      the last month of pregnancy was taken from antenatal records and parents were
      interviewed to identify preferred lying posture in the first year of life. At the
      time of the physical assessment ages ranged from 1 year and 1 month to 19 years
      with a median age of 13 years and 1 month. RESULTS: Foetal presentation was found
      to be associated with the preferred lying posture with participants carried in a
      left occipito-anterior/lateral position more likely to adopt a supine head right
      lying posture, and vice versa. An association was also observed between the
      foetal position and asymmetrical postural deformity occurring later in life with
      participants carried in a left occipito-anterior/lateral presentation more likely
      to have a convex left spinal curve, a lower left pelvic obliquity, and a
      windswept hip pattern to the right. CONCLUSIONS: Clinicians should be aware of
      the association between foetal presentation, asymmetrical lying posture, and the
      direction of subsequent postural deformity for severely disabled children. A
      hypothesis is described that might help to explain these findings.

PMID- 20030661
TI  - Experimental hookworm infection: a randomized placebo-controlled trial in asthma.
AB  - BACKGROUND: Epidemiological studies suggest that hookworm infection protects
      against asthma, and therefore that hookworm infection may have a direct or an
      indirect therapeutic potential in this disease. We now report the first clinical
      trial of experimental hookworm infection in people with allergic asthma.
      OBJECTIVES: To determine the effects of experimental hookworm infection in
      asthma. METHODS: Thirty-two individuals with asthma and measurable airway
      responsiveness to adenosine monophosphate (AMP) were randomized and double
      blinded to cutaneous administration of either ten Necator americanus larvae, or
      histamine solution (placebo), and followed for 16 weeks. The primary outcome was
      the change in provocation dose of inhaled AMP required to reduce forced
      expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary
      outcomes included change in several measures of asthma control and allergen skin
      sensitivity and the occurrence of adverse effects. RESULTS: Mean PD(20)AMP
      improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the
      placebo group (0.98 DD), but the difference between groups was not significant
      (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no
      significant differences between the two groups for other measures of asthma
      control or allergen skin sensitization. Infection was generally well tolerated.
      CONCLUSIONS: Experimental infection with ten hookworm larvae in asthma did not
      result in significant improvement in bronchial responsiveness or other measures
      of asthma control in this study. However, infection was well tolerated and
      resulted in a non-significant improvement in airway responsiveness, indicating
      that further studies that mimic more closely natural infection are feasible and
      should be undertaken.

PMID- 20030662
TI  - Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and
      ILT4 in cord blood.
AB  - BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect
      against the development of atopic diseases in young children. Vitamin D has been
      shown to induce tolerogenic antigen-presenting cells such as dendritic cells.
      Whether the allergy-protective potential of prenatal vitamin D is mediated
      through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the
      association between prenatal vitamin D supplementation and tolerogenic antigen
      presenting cells in cord blood (CB) as determined by mRNA measurement of
      immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi
      centre birth cohort was established in rural areas of five European countries.
      Information on maternal exposures including vitamin D intake was collected by
      questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was
      analysed by real-time PCR in the CB of 927 children. Maternal vitamin D
      supplementation was assessed in Finland and France (n=349). RESULTS: Maternal
      vitamin D supplementation during pregnancy was associated with an increase in the
      gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained
      significant for ILT4 (P=0.020) and showed a positive trend for the gene
      expression of ILT3 (P=0.059) after multivariate analysis controlling for various
      confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase
      the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early
      induction of tolerogenic immune responses by maternal vitamin D intake.

PMID- 20030663
TI  - Processing-dependent and -independent pathways for recognition of iodinated
      contrast media by specific human T cells.
AB  - BACKGROUND: One to three percent of patients exposed to intravenously injected
      iodinated contrast media (CM) develop delayed hypersensitivity reactions.
      Positive patch test reactions, immunohistological findings, and CM-specific
      proliferation of T cells in vitro suggest a pathogenetic role for T cells. We
      have previously demonstrated that CM-specific T cell clones (TCCs) show a broad
      range of cross-reactivity to different CM. However, the mechanism of specific CM
      recognition by T cell receptors (TCRs) has not been analysed so far. OBJECTIVE:
      To determine how T cells specifically recognize CM. METHODS: CM-specific TCCs
      were generated from human blood of three CM-allergic patients and a specific TCR
      was transfected into a mouse T cell hybridoma. Functional analysis such as
      proliferation assays, IL-2 secretion assays, and calcium influx experiments were
      performed using irradiated, glutaraldehyde-fixed, CM-pre-incubated, human
      leucocyte antigen (HLA)-DR-matched or -mismatched antigen-presenting cells
      (APCs), and HLA-blocking antibodies. RESULTS: We identified two mechanisms of T
      cell stimulation: some TCCs and the transfectant reacted to CM independent of
      uptake by APCs because proliferation/IL-2 secretion occurred in the presence of
      glutaraldehyde-fixed APCs, and intracellular calcium increased within seconds
      after drug addition. Other TCCs required functional APCs, compatible with uptake
      and presentation of CM on MHC-class II molecules, as implied by three findings:
      (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be
      washed away from CM-pre-incubated APCs; and (3) the optimal pulsing time was 10
      20 h. Because allogeneic, MHC-matched, CM-pulsed APCs could induce proliferative
      responses as well, the ability of CM uptake and presentation is not unique to
      APCs from patients with CM-induced delayed hypersensitivity. CONCLUSION: Our data
      suggest that CM may be stimulatory for T cells either by direct binding to the
      MHC-TCR complex or by binding after uptake and processing by APCs. This questions
      the assumed inert nature of CM.

PMID- 20030664
TI  - Airway smooth muscle proliferation and survival is not modulated by mast cells.
AB  - BACKGROUND: Airway smooth muscle (ASM) hyperplasia and mast cell localization
      within the ASM bundle are important features of asthma. The cause of this
      increased ASM mass is uncertain and whether it is a consequence of ASM-mast cell
      interactions is unknown. OBJECTIVE: We sought to investigate ASM proliferation
      and survival in asthma and the effects of co-culture with mast cells. METHODS:
      Primary ASM cultures were derived from 11 subjects with asthma and 12 non
      asthmatic controls. ASM cells were cultured for up to 10 days in the presence or
      absence of serum either alone or in co-culture with the human mast cell line-1,
      unstimulated human lung mast cells (HLMC) or IgE/anti-IgE-activated HLMC.
      Proliferation was assessed by cell counts, CFSE assay and thymidine
      incorporation. Apoptosis and necrosis were analysed by Annexin V/propidium iodide
      staining using flow cytometry and by assessment of nuclear morphology using
      immunofluorescence. Mast cell activation was confirmed by the measurement of
      histamine release. RESULTS: Using a number of techniques, we found that ASM
      proliferation and survival was not significantly different between cells derived
      from subjects with or without asthma. Co-culture with mast cells did not affect
      the rate of proliferation or survival of ASM cells. CONCLUSION: Our findings do
      not support a role for increased airway smooth proliferation and survival as the
      major mechanism driving ASM hyperplasia in asthma.

PMID- 20030666
TI  - Expression of neuropeptides and their degrading enzymes in ACD.
AB  - BACKGROUND: Sensory neuropeptides such as neurokinin A or substance P modulate
      skin and immune cells the functions of neurokinin receptor activation during
      neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase
      (NEP) and angiotensin-converting enzyme (ACE), effectively control the
      bioavailability of these neuropeptide mediators, which are released from sensory
      nerves, immune and skin cells during cutaneous responses to endogenous or
      exogenous noxious stimuli. Recently, studies have suggested that neuropeptides
      are one of the major pathogenetic fact in many dermatoses, such as allergic
      contact dermatitis (ACD), atopic dermatitis and psoriasis. AIM: To investigate
      the expression of major neuropeptides, SP and its degrading enzymes such as NEP
      and ACE, in the lesions of ACD. METHODS: A skin biopsy was obtained from 10
      patients with ACD. We analysed the expression of these molecules by
      immunohistochemical staining, confocal laser scanning microscopy, western
      blotting and reverse transcription PCR. RESULTS: There was a significant increase
      in expression of SP in keratinocytes from ACD lesions compared with those in
      control skin. There was also increased expression of ACE but not NEP in ACD.
      CONCLUSION: Neuropeptides and their degrading enzymes, particularly SP and ACE,
      have a significant role in the pathogenesis of ACD.

PMID- 20030665
TI  - Interleukin-13 directly promotes oesophagus production of CCL11 and CCL24 and the
      migration of eosinophils.
AB  - BACKGROUND: Eosinophilic oesophagitis (EE) is a clinico-pathologically defined
      oesophageal disorder that is characterized by eosinophil migration into
      oesophageal tissues. There is growing support for EE being an allergic disease
      and for a contribution of T-helper type 2 (Th2)-associated cytokines in disease
      pathogenesis. The respiratory system has been shown to be critical in driving the
      development of EE in animal models. However, the mechanisms underlying the
      recruitment of eosinophils into the oesophagus remain unclear. OBJECTIVE: We
      sought to investigate the influence of Th2-associated cytokines on the production
      of eosinophil-specific chemokines from the oesophagus directly. METHODS: In order
      to eliminate the potential involvement of the lung, we utilized isolated
      oesophageal rings. These were treated in vitro with IL-4 or IL-13 and the
      expression and production of CCL11 and CCL24 were determined. RESULTS: Our data
      demonstrate that IL-13 is a potent and direct inducer of both CCL11 and CCL24
      production from the oesophagus, as is IL-4 also. The expression of CCL11 precedes
      CCL24 by several hours but then diminishes over time, as well as at high
      concentrations of IL-13. We demonstrate that there is an up-regulation of the
      inhibitory IL-13 receptor, IL-13Ralpha2 but that IL-13Ralpha1 remains unaltered.
      Oesophagus rings isolated from STAT6(-/-) mice were unable to produce CCL11 or
      CCL24 upon IL-13 treatment. Lastly, we demonstrate that oesophageal production of
      CCL11 and CCL24 upon IL-13 stimulation is sufficient to promote eosinophil
      migration. CONCLUSIONS: IL-13 is capable of directly stimulating oesophageal
      tissue to produce eosinophil-attracting chemokines and drive eosinophil
      migration.

PMID- 20030667
TI  - A guide to anticoagulation and endocarditis prophylaxis during cutaneous surgery.
AB  - Management of perioperative antiplatelet/anticoagulation drugs and appropriate
      antibiotic prophylaxis for endocarditis are two controversial issues in the safe
      practice of cutaneous surgery. This article highlights the current best practice
      based on a literature review on these topics. Antiplatelet agents should be
      continued perioperatively whenever clinically possible, and discontinued only
      after consultation with the patient's cardiologist. The exception to this is
      primary cardiovascular disease, when antiplatelet drugs should be stopped for 1
      week before surgery. Warfarin can be continued perioperatively when the
      international normalised ratio is controlled at < 3. The use of antibiotics in
      patients at risk of endocarditis has been recently reviewed by the National
      Institute of Health and Clinical Excellence (NICE), the American Heart
      Association, and the European Society of Cardiology. The advice has changed
      significantly over the past few years, and the routine use of antibiotics
      perioperatively should occur only when there is evidence of infection
      perioperatively at the site of surgery.

PMID- 20030668
TI  - Calreticulin is a B cell molecular target in some gastrointestinal malignancies.
AB  - Calreticulin, upon translocation to the cell surface, plays a critical role in
      the recognition of tumour cells and in experimentally induced cellular anti
      tumour immunity. However, less is known about anti-calreticulin antibodies and
      their role in malignancies. Using enzyme-linked immunosorbent assay (ELISA), we
      found immunoglobulin (Ig)A and/or IgG anti-calreticulin antibodies in sera of
      approximately 63% of patients with hepatocellular carcinoma (HCC), 57% of
      patients with colorectal adenocarcinoma (CRA) and 47% of patients with pancreatic
      adenocarcinoma (PACA), while healthy controls, patients with viral hepatitis C
      and with chronic pancreatitis reached only 2%, 20% and 31% seropositivity,
      respectively. We found significantly elevated mean levels of IgA anti
      calreticulin antibodies (P < 0.001) in patients with HCC (78.7 +/- 52.3 AU, mean
      +/- standard deviation), PACA (66.5 +/- 30.9 AU) and CRA (61.8 +/- 25.8 AU) when
      compared to healthy controls (41.4 +/- 19.2 AU). Significantly elevated mean
      levels of IgG anti-calreticulin antibodies (P < 0.001) were detected in patients
      with HCC (121.9 +/- 94.2 AU), gall bladder adenocarcinoma (118.4 +/- 80.0 AU) and
      PACA (88.7 +/- 55.6 AU) when compared to healthy controls (56.7 +/- 22.9 AU).
      Pepscan analysis revealed a large number of antigenic epitopes of calreticulin
      recognized by both IgA and IgG antibodies of patients with HCC and PACA,
      indicating robust systemic immune response. Moreover, significantly elevated
      levels of antibodies against peptide KGEWKPRQIDNP (P < 0.001) in these patients,
      tested by ELISA, confirmed the distinct character of antibody reactivity against
      calreticulin. The high occurrence and specificity of serum anti-calreticulin
      autoantibodies in the majority of patients with some gastrointestinal
      malignancies provide the evidence for their possible clinical relevance.

PMID- 20030669
TI  - Vitamin K3 attenuates lipopolysaccharide-induced acute lung injury through
      inhibition of nuclear factor-kappaB activation.
AB  - Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin
      K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was
      reported that vitamin K, especially vitamins K1 and K2, exerts a variety of
      biological effects, and these compounds are expected to be candidates for
      therapeutic agents against various diseases. In this study, we investigated the
      anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and
      in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3
      inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear
      factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin
      K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of
      NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells.
      Moreover, the addition of vitamin K3 before and after LPS administration
      attenuated the severity of lung injury in an animal model of acute lung
      injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of
      acute severe illness complicated by systemic inflammation. In the ARDS model,
      vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level
      and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue.
      Despite marked efforts, little therapeutic progress has been made, and the
      mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic
      strategy against acute lung injury including ARDS.

PMID- 20030670
TI  - Dendritic cells pulsed with antigen-specific apoptotic bodies prevent
      experimental type 1 diabetes.
AB  - Dendritic cells (DCs) are powerful antigen-presenting cells capable of
      maintaining peripheral tolerance. The possibility to generate tolerogenic DCs
      opens new therapeutic approaches in the prevention or remission of autoimmunity.
      There is currently no treatment inducing long-term tolerance and remission in
      type 1 diabetes (T1D), a disease caused by autoimmunity towards beta cells. An
      ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side
      effects and allow islet regeneration. Apoptotic cells--a source of autoantigens-
      are cleared rapidly by macrophages and DCs through an immunologically silent
      process that contributes to maintaining tolerance. Our aims were to prevent T1D
      and to evaluate the re-establishment of peripheral tolerance using autologous DCs
      pulsed in vitro with apoptotic bodies from beta cells. Immature DCs derived from
      bone marrow of non-obese diabetic (NOD) mice were obtained and pulsed with
      antigen-specific apoptotic bodies from the beta cell line NIT-1. Those DCs that
      phagocytosed apoptotic cells diminished the expression of co-stimulatory
      molecules CD40 and CD86 and reduced secretion of proinflammatory cytokines.
      Moreover, these cells were resistant to increase the expression of co-stimulatory
      molecules after lipopolysaccharide activation. The administration of these cells
      to NOD transgenic mice expressing interferon-beta in their insulin-producing
      cells, a model of accelerated autoimmune diabetes, decreased diabetes incidence
      significantly and correlated positively with insulitis reduction. DCs pulsed with
      apoptotic cells that express disease-associated antigens constitutes a promising
      strategy to prevent T1D.

PMID- 20030671
TI  - T-cell activation profiles in different granulomatous interstitial lung diseases-
      a role for CD8+CD28(null) cells?
AB  - Lymphocytes play a crucial role in lung inflammation. Different interstitial lung
      diseases may show distinct lymphocyte activation profiles. The aim of this study
      was to examine the expression of a variety of activation markers on T lymphocyte
      subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with
      different granulomatous interstitial lung diseases and healthy controls.
      Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven
      patients with hypersensitivity pneumonitis and 24 healthy controls were analysed.
      Lymphocyte activation status was determined by flow cytometry. Lymphocytes were
      stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late
      antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In
      general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR
      expression on BALF CD8+ lymphocytes was different in patients with
      hypersensitivity pneumonitis and sarcoidosis patients with parenchymal
      involvement. This BALF lymphocyte phenotype correlated with carbon monoxide
      diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2
      = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes
      correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte
      activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I
      versus stage II and higher, P = 0.006) and with the need for corticosteroid
      treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower
      expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic
      lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null)
      cells might be a new biomarker for disease severity but needs further
      investigation.

PMID- 20030674
TI  - Tactile sensibility of single-tooth implants and natural teeth under local
      anesthesia of the natural antagonistic teeth.
AB  - INTRODUCTION AND AIM: The term osseoperception describes the capability of
      developing a subtle tactile sensibility over dental implants. The present
      clinical study aims at clarifying the question of how far tactile sensibility is
      to be attributed to the periodontium of the natural opposing tooth of the
      implant. MATERIAL AND METHOD: Thirty-two subjects with single-tooth implants with
      natural opposing teeth were included in this clinical, single-blind, split-mouth
      study. The natural antagonistic tooth of the implant and the corresponding
      natural contralateral tooth were anesthetized with a locally infiltrated
      articaine anesthetic. In a computer-assisted and randomized way, copper foils of
      varying thickness (0-100 um) were placed interocclusally between the single-tooth
      implant and the natural opposing tooth, and between the contralateral pair of
      natural opposing teeth in order to investigate the active tactile sensibility
      according to the psychophysical method of constant stimuli and evaluate it
      statistically by the Weibull distribution. RESULTS: The average tactile
      sensibility of the implants with anesthetized antagonists at the 50% value
      calculated by means of the Weibull distribution was 20 +/- 11 um with a support
      area (90%-10% value) of 77 +/- 89 um. For the pair of natural teeth, the tactile
      sensibility at the 50% value was 16 +/- 9 um with a support area of 48.4 +/- 93
      um. This resulted in an average intraindividual difference of 3.5 +/- 7 um at the
      50% value and 29 +/- 93 um in the support area. The statistical calculations
      demonstrated an equivalent tactile sensibility (50% value) of the single-tooth
      implant and the contralateral natural control tooth with the natural antagonists
      being anesthetized in each case (double t-test, equivalence limit +/- 8 um, P <
      0.01, power >80%). CONCLUSION: Apparently, the active tactile sensibility of
      single-tooth implants with natural opposing teeth is not only to be attributed to
      the periodontium of the opposing tooth but also to a perception over the implant
      itself. This could support the hypothesis according to which the implant may have
      a tactile sensibility of its own.

PMID- 20030672
TI  - Immune response to Plasmodium vivax has a potential to reduce malaria severity.
AB  - Plasmodium falciparum infection causes transient immunosuppression during the
      parasitaemic stage. However, the immune response during simultaneous infections
      with both P. vivax and P. falciparum has been investigated rarely. In particular,
      it is not clear whether the host's immune response to malaria will be different
      when infected with a single or mixed malaria species. Phenotypes of T cells from
      mixed P. vivax-P. falciparum (PV-PF) infection were characterized by flow
      cytometry, and anti-malarial antibodies in the plasma were determined by an
      enzyme-linked immunosorbent assay. We found the percentage of CD3+delta2+-T cell
      receptor (TCR) T cells in the acute-mixed PV-PF infection and single P. vivax
      infection three times higher than in the single P. falciparum infection. This
      implied that P. vivax might lead to the host immune response to the production of
      effector T killer cells. During the parasitaemic stage, the mixed PV-PF infection
      had the highest number of plasma antibodies against both P. vivax and P.
      falciparum. Interestingly, plasma from the group of single P. vivax or P.
      falciparum malaria infections had both anti-P. vivax and anti-P. falciparum
      antibodies. In addition, antigenic cross-reactivity of P. vivax or P. falciparum
      resulting in antibodies against both malaria species was shown in the supernatant
      of lymphocyte cultures cross-stimulated with either antigen of P. vivax or P.
      falciparum. The role of delta2 +/- TCR T cells and the antibodies against both
      species during acute mixed malaria infection could have an impact on the immunity
      to malaria infection.

PMID- 20030673
TI  - High density of intraepithelial gammadelta lymphocytes and deposits of
      immunoglobulin (Ig)M anti-tissue transglutaminase antibodies in the jejunum of
      coeliac patients with IgA deficiency.
AB  - The diagnosis of coeliac disease (CD) represents a special challenge in selective
      immunoglobulin (Ig)A deficiency (IgAD). A high density of T cell receptor
      (TCR)gammadelta(+) intraepithelial lymphocytes (IELs) and intestinal IgA anti
      tissue transglutaminase 2 (anti-TG2) antibody deposits are suggestive of CD. We
      analysed the density of TCRgammadelta(+) IELs and the deposition of IgM anti-TG2
      antibodies in the jejunal mucosa of IgAD patients with and without CD.
      Immunohistochemical analyses for the number of CD3+ and TCRgammadelta(+) IELs and
      double immunofluorescence assay for IgM anti-TG2 antibody deposits were performed
      in biopsies from 25 children with IgAD (nine untreated CD, seven potential CD and
      nine without CD). Sixteen immunologically intact children without CD represented
      the controls. IgAD without CD had a higher number of CD3+ and TCRgammadelta(+)
      IELs than controls (P < 0.05), but lower than IgAD with CD (P < 0.01). No
      significant differences were noted between IgAD subjects without CD and those
      with potential CD. Furthermore, IgAD patients without CD showed a higher
      TCRgammadelta(+)/CD3+ ratio than the control group (P < 0.05), while the ratio
      was similar to subjects with CD and potential CD. Intestinal IgM anti-TG2
      antibody deposits were present in six of seven of the IgAD patients with
      untreated CD, one of seven with potential CD and none of those without CD. Most
      of the patients with IgAD show immune activation in the jejunal mucosa. IgM anti
      TG2 antibody deposits are present only in CD. Intestinal IgM anti-TG2 and
      immunohistochemical markers do not discriminate between IgAD and potential CD
      with IgAD. Therefore, the serum IgG CD-associated autoantibodies remains very
      important for the diagnosis of CD in IgAD.

PMID- 20030675
TI  - Clinical evaluation of 209 all-ceramic single crowns cemented on natural and
      implant-supported abutments with different luting agents: a 6-year retrospective
      study.
AB  - BACKGROUND: The Procera AllCeramTM system (Nobel Biocare AB, Goteborg, Sweden) is
      a valid alternative to metal-ceramic restorations. However, limited long-term
      data of its use for single crowns on natural and implant-supported abutments are
      available. PURPOSE: The present study aimed at evaluating the clinical
      performances of Procera AllCeram single crowns in both anterior and posterior
      regions of the oral cavity either on natural tooth or implant abutments over a
      period of 6 years. MATERIALS AND METHODS: Two hundred nine single crowns were
      fabricated and used in 112 patients. Zinc phosphate and resin luting agents were
      used to cement the restorations. The crowns were evaluated according to the
      California Dental Association's quality assessment system. RESULTS: Three crowns
      were lost at follow-up. Of the 206 restorations, which completed the 6-year
      follow-up, 9 crowns were affected by mechanical complications and 7 crowns
      failed. All surviving crowns were ranked as either excellent or acceptable.
      Cumulative survival and success rates of 95.2 and 90.9%, respectively, were
      recorded. CONCLUSIONS: Within the limitations of the present study, Procera
      AllCeram crowns proved to be a reliable clinical option to restore both anterior
      and posterior missing teeth either on natural or implant abutments. The resin
      cement used in the present study performed better than the zinc phosphate luting
      agent.

PMID- 20030676
TI  - Prevalence and severity of renal dysfunction among 1062 heart transplant patients
      according to criteria based on serum creatinine and estimated glomerular
      filtration rate: results from the CAPRI study.
AB  - Chronic kidney disease (CKD) is staged on the basis of glomerular filtration
      rate; generally, the MDRD study estimate, eGFR, is used. Renal dysfunction (RD)
      in heart transplant (HT) patients is often evaluated solely in terms of serum
      creatinine (SCr). In a cross-sectional, 14-center study of 1062 stable adult HT
      patients aged 59.1+/-12.5 yr (82.3% men), RD was graded as absent-or-mild (AoM),
      moderate, or severe (this last including dialysis and kidney graft) by two
      classifications: SCr-RD (SCr cutoffs 1.6 and 2.5 mg/dL) and eGFR-RD (eGFR cutoffs
      60 and 30 mL/min/1.73 m2). SCr-RD was AoM in 68.5% of patients, moderate in
      24.9%, and severe in 6.7%; eGFR-RD, AoM in 38.6%, moderate in 52.2%, severe in
      9.2%. Among patients evaluated <2.7, 2.7-6.2, 6.2-9.5 and >9.5 yr post-HT (the
      periods defined by time-since-transplant quartiles), AoM/moderate/severe RD
      prevalences were <2.7, SCr-RD 74/21/5%, eGFR-RD 47/47/6%; 2.7-6.2, SCr-RD
      73/22/5%, eGFR-RD 37/56/7%; 6.2-9.5, SCr-RD 69/24/7%, eGFR-RD 37/54/9%; >9.5, SCr
      RD 58/32/10%, eGFR-RD 32/52/16%. The prevalence of severe RD increases with time
      since transplant. If the usual CKD stages are appropriate for HT patients, the
      need for less nephrotoxic immunosuppressants and other renoprotective measures is
      greater than is suggested by direct SCr-based grading, which should be abandoned
      as excessively insensitive.

PMID- 20030677
TI  - Soluble cytokeratin 18 biomarkers may provide information on the type of cell
      death during early ischemia and reperfusion periods of liver transplantation.
AB  - Hepatocellular damage takes place as a result of ischemia and reperfusion during
      liver transplantation (LT). To discriminate the type of cell death and quantitate
      its severity may provide new insights into the mechanisms of hepatocellular
      damage. Therefore, we investigated the type of cell death by ELISA-based assays
      in patient sera. Apoptosis was specifically assessed by measuring a novel soluble
      biomarker, the caspase-cleaved cytokeratin 18, while total cell death (apoptosis
      and necrosis) by cytokeratin 18 released from dead (necrotic and apoptotic)
      cells. Twenty-seven live (LDLT) and 14 deceased (DDLT) donor liver
      transplantations were analyzed before the operation, at the anhepatic stage,
      first, sixth and 24th hour after the reperfusion. Both apoptosis and total cell
      death have successfully been demonstrated although they have not been confirmed
      by the liver biopsy that is impossible to perform in this setting. Apoptosis was
      not induced in LDLT. Total cell death (primarily necrosis) only transiently
      appeared the first hour after the reperfusion in LDLT, while it sharply increased
      the first hour after the reperfusion and maintained its level in DDLT. Soluble
      cytokeratin 18 biomarkers seem to be useful to discriminate and quantitate the
      type of cell death during early ischemia and reperfusion periods of LT.

PMID- 20030678
TI  - Association of plasma pentosidine concentrations with renal function in kidney
      graft recipients.
AB  - BACKGROUND: Advanced glycation end-products accumulate in the plasma of uremic
      patients. We aimed to assess the changes of free (P(free)) and total (P(tot))
      plasma pentosidine concentrations in kidney graft recipients, create a model
      describing their profile and analyze associations with clinical parameters.
      MATERIAL AND METHODS: We measured P(free) and P(tot) in the plasma of 12 non
      diabetic patients before and after kidney transplantation by HPLC. RESULTS: P
      (tot) concentrations were significantly decreasing after transplantation. The
      changes were well described by the exponential model assuming an asymptotic fall
      until the steady-state concentration is attained. P(tot) before and after
      transplantation displayed a strong negative correlation with mean daily diuresis
      (Rs = -0.64, p < 0.05 before; Rs = -0.94, p < 0.01 after 20 d). The rate of fall
      of the P(tot) was positively correlated with the mean daily volume of urine
      passed in the second week after operation (Rs = +0.58, p < 0.05). CONCLUSIONS:
      The rate of fall of the P(tot) after transplantation displays a strong
      correlation with diuresis, and the P(tot) before transplantation is a potential
      prognostic factor for diuresis after the operation. Further prospective studies
      are necessary to demonstrate whether an effort to reduce carbonyl stress and
      pentosidine concentration before transplantation improves renal outcome.

PMID- 20030679
TI  - In vitro isolation of stem cells derived from human dental pulp.
AB  - Stem cells are characterized by the ability to differentiate and to self-renew.
      Stem cells derived from human dental pulp have been shown to differentiate into
      osteoblasts serving as a potential source of autologous bone produced in vitro.
      The purpose of the present study was to isolate mesenchymal stem cells from
      dental pulp. Dental pulp was gently extracted from 27 intact human permanent
      third molars of patients aged 18-25. Cow horn forceps were used to isolate intact
      dental pulp in sterilized condition. The pulps were cultured in a medium
      containing Dulbecco's modified Eagle's medium-low glucose (DMEM)-LG and
      Amphotericin 1%. The cells were subsequently expanded by passages, two passages
      were performed before they were stored in liquid nitrogen for further
      examination. DMEM + fetal bovine serum (FBS) 10% L-Glutamin 0.1% + Trypsin 2.5% +
      ethylene diamine tetraacetic acid (EDTA) were used for passage. Light microscope
      and flow cytometry were used to study the cells. The isolated dental pulp cells
      expressed mesenchymal stem cell markers. The cells were negative for CD34 and
      CD31 and CD45 but were positive for CD13, CD44, CD90, CD166, and CD105. These
      results indicate that dental pulp can be use as a source of stem cells that we
      can isolate and culture.

PMID- 20030680
TI  - Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related
      neurotoxicity after hematopoietic stem cell transplantation.
AB  - BACKGROUND: One severe side effect of calcineurin inhibitors (CNIs: such as
      cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates
      for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present
      study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be
      associated with CNI-related neurotoxicity. METHODS: The effects of the
      polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T,
      associated with CNI-related neurotoxicity were evaluated in 63 patients with
      hematopoietic stem cell transplantation. RESULTS:   Of the 63 cases, 15 cases
      developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p =
      0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p
      < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC
      genotype at ABCB1 C1236T was associated with it, but not significantly so (p =
      0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506
      patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002)
      were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G
      (expressor genotype) was strongly associated with it according to logistic
      regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4-51.4). CONCLUSION:   The
      polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related
      neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or
      metabolites of CNIs.

PMID- 20030681
TI  - The influence of OKT3 therapy on hepatocellular carcinoma recurrence following
      liver transplantation.
AB  - INTRODUCTION: Cancer recurrence following orthotopic liver transplantation (OLT)
      for hepatocellular carcinoma (HCC) is a significant obstacle in up to 10-20% of
      recipients. Recent evidence suggests that anti-CD3 antibody (OKT3) therapy may be
      associated with increased rates of HCC recurrence. METHODS: At the University of
      Colorado Transplant Center, 173 patients underwent OLT for end-stage liver
      disease with concomitant HCC between 1997 and 2008. Nine clinical and pathologic
      variables were analyzed to test the association between OKT3 therapy for steroid
      resistant rejection (SRR) and HCC recurrence-free survival. RESULTS: Overall, the
      rate of HCC recurrence in this cohort was low and comparable across treatment
      groups (8.7%). Multivariate analysis reveals that increasing tumor diameter and
      differentiation have a negative impact on HCC recurrence-free survival.
      CONCLUSIONS: While several pathologic variables appear to influence outcome, we
      found no association between OKT3 therapy for SRR and HCC recurrence or survival.

PMID- 20030682
TI  - Improvement of sleep-related breathing disorder in patients with end-stage renal
      disease after kidney transplantation.
AB  - Sleep-related breathing disorder (SRBD) is a common symptom of end-stage renal
      disease (ESRD). The aim of this study was to determine whether kidney
      transplantation improves SRBD. Twenty-four patients with ESRD, who were admitted
      for kidney transplantation, underwent a sleep study using a portable ventilation
      effort recorder on the night before transplantation. Of these patients, 20 could
      repeat the overnight monitoring two wk after the transplantation. The median
      apnea-hypopnea index (AHI) of the 20 patients was 13.5 (range, 2-40), and
      significantly reduced to 4.5 (range, 0-20) after transplantation (p = 0.003).
      This reduction was most prominent in 12 patients with SRBD, for whom the median
      AHI fell from 22 (range, 10-40) to 6.5 (range, 1-20; p = 0.010). SRBD
      improvement, defined as an AHI equal to or >50% and/or reduced to <10/h, was
      observed in eight of the 12 apneic patients. These results suggest that kidney
      transplantation may immediately improve SRBD in patients with ESRD. However,
      conclusions from this study should be taken with caution because of the
      limitations of our method, specifically the use of a portable recorder and a
      small number of patients.

PMID- 20030683
TI  - A single-center retrospective analysis of liver transplantation on 255 patients
      with hepatocellular carcinoma.
AB  - BACKGROUND: Liver transplantation (LT) was advocated as a salvage treatment of
      choice for patients with unresectable hepatocellular carcinoma (HCC). This study
      was designed to assess the eligibility of LT criteria for patients with HCC and
      to analyze the factors influencing the recurrence of HCC following LT, aiming to
      further improve the efficacy of LT for patients with HCC. METHODS: Clinical data
      of 255 patients with HCC who underwent LT between December 2001 and December 2007
      at Shanghai Changzheng Hospital, China were retrospectively analyzed. RESULTS:
      Among these cases, 75 patients were within the Milan criteria and 180 were beyond
      it; 110 patients were within the University of California, San Francisco (UCSF)
      criteria, while 145 were beyond it. The difference in overall survival rates was
      not only significant between the patients within and beyond the Milan criteria
      but also between patients within and beyond the UCSF criteria. Tumor-node
      metastasis (TNM) staging, portal vein tumor thrombus (PVTT), and the pre
      operative alpha-fetoprotein (AFP) level were independent risk factors affecting
      the overall survival and post-operative recurrence-free survival rates of
      patients with HCC. Pathological staging and pre-operative local treatment of HCC
      had no obvious correlation with the post-operative recurrence-free survival rate.
      CONCLUSION: LT is an effective treatment modality for HCC. The UCSF criteria did
      not show better effectiveness than the Milan criteria. TNM staging, PVTT, and the
      pre-operative AFP level are closely related to the recurrence of HCC following
      LT.

PMID- 20030684
TI  - Early (fifth day) vs. late (sixth month) steroid withdrawal in renal transplant
      recipients treated with Neoral((r)) plus Rapamune((r)): four-yr results of a
      randomized monocenter study.
AB  - The most advisable timing for steroid withdrawal (CSWD) after renal
      transplantation (Tx) is still an open issue. This randomized study has compared
      early CSWD (at day 5) with late (at month 6) in patients under Neoral +
      Sirolimus. The primary end point was the percentage of success in CSWD at month
      48. Ninety-six transplants from deceased donors were randomized to withdraw
      steroids either early (n = 49) or late (n = 47). At four yr, the two strategies
      were comparable for: success in CSWD (65% in both), graft survival (95% and 98%),
      patient survival (92% and 96%) creatininemia (1.7 +/- 0.3 and 1.6 +/- 0.4 mg/dL),
      side effects, being still on Sirolimus + Neoral (69% and 74%), reversibility of
      rejection (AR) (all cases), severity of AR (grade 1A/1B: 81% and 63%). The major
      differences were incidence of AR: at month twelve (48% vs. 30%, p < 0.04), at 48
      (53% and 33%, p < 0.03); timing of AR (72 +/- 86 d vs. 202 +/- 119 d, p <
      0.0001). The timing of CSWD influences neither the rate of successful CSWD nor
      the long-term results. However, early suspension causes a higher AR rate, mostly
      arising within month one, but always responsive to steroids. Yet, the early
      appearance of AR can make patient management easier and safer.

PMID- 20030685
TI  - The terms diplegia and quadriplegia should not be abandoned.

PMID- 20030687
TI  - Echocardiographic detection of atrial septal defects: the forgotten view.
AB  - The right parasternal view is conventionally used to assess the aortic valve and
      the ascending aorta. We describe two cases in which the right parasternal view
      was helpful in assessment of the interatrial septum and the detection of atrial
      septal defects (ASD), including one case in which this view confirmed the
      presence of a defect not seen in any other echocardiographic view. Use of the
      right parasternal view should be considered for assessment of the interatrial
      septum, particularly when there is a high index of suspicion for an atrial septal
      defect but no defect is seen on conventional views. It should also be used to
      exclude the possibility of multiple defects even when an ASD is visualized using
      conventional imaging planes.

PMID- 20030688
TI  - 3D Transesophageal echocardiographic guidance and monitoring of percutaneous
      aortic valve replacement.
AB  - We describe a preliminary clinical experience with 3D transesophageal
      echocardiography (3D TEE) in an 84-year-old man with severe aortic stenosis and
      multiple comorbidity, who underwent percutaneous aortic valve implantation.
      Although 3D TEE monitoring is not a standard procedure during aortic valve
      replacement procedure (PAVR), when used in combination with conventional 2D-TEE
      contributes to improving adequate patient selection and provides more accurate
      information to the interventional cardiologist during positioning, deployment,
      and early function of the prosthesis.

PMID- 20030689
TI  - Preoperative right ventricular function in patients with organic mitral
      regurgitation.
AB  - AIMS: To assess the right ventricular (RV) function in patients with severe
      mitral regurgitation (MR); to find a relation between preoperative and
      postoperative parameters. METHODS: RV function was echocardiographically assessed
      by determining the tricuspid annular plane systolic excursion (TAPSE) and the
      peak systolic velocity of the lateral tricuspid annulus (Sa) in 45 patients with
      severe organic MR (53.3% men, age 58 +/- 10 years). Mean NYHA class was 2.6 +/-
      0.4, LVEF was 55.3 +/- 12%, RV end-diastolic diameter was 28.7 +/- 4.7, left
      ventricular end-systolic diameter (LVESD) was 44.6 +/- 12.6 mm, and LV end
      diastolic volume (Simpson) was 160.6 +/- 50.3 ml. All patients underwent mitral
      valve replacement with posterior chordal sparing. RESULTS: Mean preoperative
      TAPSE and Sa were 19.4 +/- 4.3 mm and 10.3 +/- 3 cm/sec, respectively. RV
      dysfunction, defined as TAPSE < 22 mm, had 66.6% of the patients, and Sa < 11
      cm/sec was found in 62.2% of the patients preoperatively. Preoperative TAPSE and
      Sa were significantly correlated (P < 0.00001, r = 0.61). Both TAPSE and Sa were
      correlated with the RV end-diastolic diameter (P < 0.01), LVESD (P < 0.05) left
      ventricular dp/dt (P < 0.05), and LVEF (P < 0.0001). Postoperative LVEF was 50%
      (P < 0.001), Sa 5.3 +/- 2 cm/sec (P < 0.001), and TAPSE 8.7 +/- 3.2mm (P <
      0.001). Twenty-one patients (46.6%) reached the study end point of decrease of
      LVEF by more than 10%. Univariate predictors were age (P = 0.04), male gender (P
      = 0.01), TAPSE (P = 0.007), and Sa (P = 0.009), while a trend was found for
      regurgitation fraction (P = 0.058) and LV end-diastolic volume index (P = 0.09).
      By multivariate analysis, TAPSE (P = 0.01) and Sa (P = 0.01) were predictive for
      the study end point. CONCLUSION: The assessment of the RV function by
      echocardiography is a simple tool that provides prognostic information in
      patients with MR.

PMID- 20030690
TI  - Clinically relevant drug interactions between anticancer drugs and psychotropic
      agents.
AB  - Drug interactions are commonly seen in the treatment of cancer patients.
      Psychotropics are often indicated for these patients since they may also suffer
      from pre-existing psychological disorders or experience insomnia and anxiety
      associated with cancer therapy. Thus, the risk of anticancer drug (ACD)
      psychotropic drug-drug interactions (DDIs) is high. Drug interactions were
      compiled from the British National Formulary (53rd edn), Lexi-Comp's Drug
      Information Handbook (15th edn), Micromedex (v5.1), Hansten & Horn's Drug
      Interactions (2000) and Drug Interaction Facts (2008 edn). Product information of
      the individual drugs, as well as documented literature on ACD-psychotropic
      interactions from PubMed and other databases was also incorporated. This paper
      identifies clinically important ACD-psychotropic DDIs that are frequently
      observed. Pharmacokinetic DDIs were observed for tyrosine kinase inhibitors,
      corticosteroids and antimicrotubule agents due to their inhibitory or inductive
      effects on cytochrome P450 isoenzymes. Pharmacodynamic DDIs were identified for
      thalidomide with central nervous system depressants, procarbazine with
      antidepressants, myelosuppressive ACDs with clozapine and anthracyclines with QT
      prolonging psychotropics. Clinicians should be vigilant when psychotropics are
      prescribed concurrently with ACDs. Close monitoring of plasma drug levels should
      be carried out to avoid toxicity in the patient, as well as to ensure adequate
      chemotherapeutic and psychotropic coverage.

PMID- 20030691
TI  - Cancer-related secondary lymphoedema due to cutaneous lymphangitis carcinomatosa:
      clinical presentations and review of literature.
AB  - Lymphoedema is a clinical condition caused by impairment of the lymphatic system,
      leading to swelling of subcutaneous soft tissues. As a result, accumulation of
      protein-rich interstitial fluid and lymphostasis often causes additional
      swelling, fibrosis and adipose tissue hypertrophy leading to progressive
      morbidity and loss of quality of life for the patient. Lymphoedema can be
      distinguished as primary or secondary. Lymphoedema is a complication frequently
      encountered in patients treated for cancer, especially after lymphadenoectomy
      and/or radiotherapy based on destruction of lymphatics. However, although
      lymphatic impairment is sometimes caused by obstructive solid metastasis, we
      present three cases of secondary lymphoedema with minor dermatological features
      without detectable solid metastasis. Sometimes this type of lymphoedema is
      mistakenly called malignant lymphoedema. All patients were previously treated for
      cancer without clinical signs of recurrence, presented with progressive
      lymphoedema and minor dermatological features of unknown origin. Clinical and
      histopathological examination of the skin revealed diffuse lymphangitis
      carcinomatosa, leading to secondary lymphoedema and adjustment of the therapeutic
      approach and prognosis. We reviewed literature on these rare presentations of
      cancer recurrence and recommend, where appropriate, consulting a dermatologist
      when discrete skin abnormalities are seen in patients with a history of cancer
      and developing lymphoedema.

PMID- 20030692
TI  - Health-related quality of life in lung cancer patients in Serbia: correlation
      with socio-economic and clinical parameters.
AB  - The objective of this study was to assess health-related quality of life (HRQoL)
      in patients with advanced non-small cell lung cancer (NSCLC). In Serbia, there is
      the lack of available data on HRQoL in lung cancer patients. The special
      attention in our study has been paid on relationships between socio-economic
      factors and HRQoL. This cross-sectional study was undertaken in group of 100
      NSCLC patients with advanced stage diseases. HRQoL was measured using three
      standard instruments: 36-item Short Form Health Survey, EORTC QLQ-C30 and its
      Lung Cancer module (EORTC QLQ-LC13). Unexpected, highly educated patients
      reported significantly worse social functioning (P=0.044), and higher degree of
      financial difficulties (P=0.047), in comparison with less-educated. Also unusual,
      unemployed patients had significantly better HRQoL in all domains and
      significantly lower symptom distress. Significantly better overall HRQoL
      (P=0.043), social (P=0.024), emotional (P=0.001) and mental functioning (P=0.011)
      were observed in patients treated with chemotherapy in comparison with newly
      diagnosed ones. In addition, the most prominent side effects of chemotherapy were
      nausea and vomiting, and all QoL domains correlated significantly with them.
      Patients who undergo active treatment improve their HRQoL but chemotherapy
      induced emesis adversely affects many HRQoL domains. Additionally, HRQoL is
      highly dependent on patient's socio-economic characteristic.

PMID- 20030693
TI  - Not telling the truth: circumstances leading to concealment of diagnosis and
      prognosis from cancer patients.
AB  - While autonomy has gradually become a key concept in the doctor-patient
      relationship, truth-telling is far from being the norm in many countries in the
      world. Despite the general agreement on the benefits of open communication
      between physicians and cancer patients, there is still strong resistance against
      disclosure of cancer diagnosis and prognosis in many cultures. Although fear of
      causing psychological morbidity to patients and their reluctance to find out the
      truth are two main justifications of non-disclosure attitudes, there are other
      important contributing factors that need to be further explored and better
      understood including those related to the relatives, doctors and healthcare
      systems. Cultural disparities in attitudes towards truth-telling persist;
      however, these differences should not be used as excuses not to respect the
      rights and individual preferences of cancer patients by making assumptions based
      on their age, sex, type of cancer, language and/or cultural background.

PMID- 20030694
TI  - VEGF mRNA expression in jugulotympanic paraganglioma.
AB  - The vascular endothelial growth factor (VEGF) family are essential regulators of
      angiogenesis and vascular permeability. VEGF protein was found in the
      jugulotympanic paraganglioma, but it wasn't confirmed on mRNA level. Our aim of
      this study is the mRNA expression of VEGF in jugulotympanic paraganglioma. We
      chose six cases of primary jugulotympanic paraganglioma wax specimen by
      hybridisation in situ. It suggested that VEGF mRNA had significant expression in
      the tumour cytoplasm of jugulotympanic paraganglioma. The correlation is not yet
      clear. It could be suggested the higher degree of malignancy, the stronger
      expression of VEGF mRNA in cytoplasm, but not found in the cellular nucleus.

PMID- 20030695
TI  - Oncological emergencies: clinical importance and principles of management.
AB  - Oncological emergencies are common conditions associated with significant
      morbidity and mortality. Delay in diagnosis and treatment can result in
      unfavourable outcomes. Cancer itself, cancer-related hormones or cytokines, or
      treatment effects can cause emergency problems. Febrile neutropaenia, frequently
      associated with chemotherapy, can lead to life-threatening conditions. Treatment
      requires systematic evaluation and early empirical antibiotics. Hypercalcaemia of
      malignancy is the most common metabolic emergency in cancer patients. Non
      specific clinical features may cause delay in diagnosis and increase morbidity
      and mortality. Treatment includes active fluid resuscitation, diuretics and
      intravenous bisphosphonates. Superior vena cava syndrome is usually caused by
      external compression. Computerised tomography is useful to confirm diagnosis,
      evaluate the extent of disease and guide invasive tissue diagnosis. Treatment and
      prognosis depend on the underlying malignancies. Spinal cord compression is a
      true emergency due to risk of permanent neurological impairment. Localised back
      pain is the most common presenting symptom while late presentation of
      neurological deficit is associated with irreversible outcomes. Magnetic resonance
      imaging is the investigation of choice. Treatment includes corticosteroids,
      radiotherapy and/or decompressive surgery.

PMID- 20030697
TI  - Anxiety and depression in cancer patients compared with the general population.
AB  - The objective of this study was to compare the prevalence of anxiety and
      depression in cancer patients with the prevalence found in the general
      population, using the Hospital Anxiety and Depression Scale (HADS). Participants
      were 1529 cancer patients treated between 2002 and 2004 in Germany and 2037
      persons from the German general population. In the cancer patients, the risk of
      psychiatric distress was nearly twice that of the general population. While for
      older age groups (61 years and above) there were only small differences between
      cancer patients and the general population, the differences in both scales were
      high for young persons. There were differences between the HADS mean scores of
      the patients with different tumour localisations, with high values for brain
      cancer and low scores for prostate cancer. The influence of the tumour stage on
      anxiety and depression was weak. However, depression scores of patients with a
      survival time less than 1 year were elevated. The results show that large sample
      sizes are necessary to evaluate the psychological situation of cancer patients,
      and that age and gender differences must be taken into account when several
      samples are compared.

PMID- 20030696
TI  - Caritas, spirituality and religiosity in nurses' coping.
AB  - The purpose of this qualitative study was to investigate registered nurses'
      coping processes when working with terminally ill and dying cancer patients, with
      special focus on religious aspects of coping resources. What religious components
      can be identified as coping resources in oncology nurses' orienting system and
      what function has religiosity in the nurse's work? The theoretical reference is
      care philosophy and the psychology of religion and coping. The material consists
      of interviews with 15 Swedish registered oncology nurses. The results highlight
      different dynamic aspects of the nurses' life orientation such as caritas,
      religiosity, spirituality and atheism and demonstrate that religiosity can have a
      protective function that facilitates coping, as the nurse has something to turn
      to. Religious coping dominated by basic trust where prayer is used as a coping
      strategy may support the nurse.

PMID- 20030698
TI  - Aflatoxin levels in common foods of South Western Uganda: a risk factor to
      hepatocellular carcinoma.
AB  - Prolonged exposure to aflatoxins by humans and animals leads to adverse effects
      to the various body systems of affected individuals including death. Studies have
      linked aflatoxins to hepatocellular carcinoma (HCC). In Uganda, HCC is observed
      to be on increase in communities of South-Western Uganda. A cross-sectional study
      was therefore conducted in five districts of the region and 90 various food
      samples were collected for total aflatoxin determination. They included ground
      nuts, cassava, millet, sorghum flour and eshabwe sauce. The aflatoxin levels were
      determined using Vicam aflatest method. The results were compared with acceptable
      European Union aflatoxin levels. Aflatoxin levels in the food samples ranged from
      0 to 55 ppb with a mean total aflatoxin level of 15.7 +/- 4.9 ppb. Eshabwe sauce
      had the highest mean total aflatoxin levels (18.6 +/- 2.4 ppb). Traditional
      methods of food processing in this study were found to be contributing risk
      factor of food contamination and hence the observed increased HCC cases and
      mortalities in the region.

PMID- 20030699
TI  - Management of chylous fistula as a complication of neck dissection: a 10-year
      retrospective review.
AB  - Chylous fistula is a serious complication of neck surgery. The aim of this study
      was to analyse the incidence, treatment and evolution of chylous fistula in neck
      dissection. We conducted a retrospective study of 304 patients, 295 (97.03%) men
      and nine (2.97%) women. Ages ranged from 24 to 80 years (mean = 59.28 years, SD =
      6.02) and they had all undergone neck dissection. Chylous fistula occurred in
      four cases (1.31%). Incidence was 1.83% in laryngeal cancer and 2.7% in oral
      cavity and oropharyngeal cancer. No statistically significant correlation was
      found between tumoral stage and fistula occurrence. Radiotherapy prior to surgery
      was a risk factor although the association was not statistically significant. The
      incidence rates for radical and functional neck dissection were 3.3% and 0.46%,
      respectively, statistically significant (P = 0.042). The fistulas were located on
      the left side in all cases. One of the four patients required surgical
      intervention and another one died. The occurrence of chylous fistula increased
      significantly the length of hospital stay (P = 0.01). Chylous fistulas appear on
      the left side, radiotherapy prior to surgery is a risk factor and there is not
      correlation with tumoral stage. Chylous fistulas are significantly more common in
      radical than in functional dissections and increase significantly the length of
      hospital stay.

PMID- 20030700
TI  - 'It's hard to take because I am a man's man': an ethnographic exploration of
      cancer and masculinity.
AB  - This paper reports on a study into male participation in cancer support groups,
      which elicited data on the impact of cancer on masculinities. This small
      qualitative pilot study, which took place in Belfast in Northern Ireland,
      involved semi-structured interviews with eight men with a history of cancer who
      were no longer being actively treated (i.e. they were not receiving chemotherapy
      or radiotherapy), and who were proficient in spoken and written English. Whereas
      most studies into men with cancer that have looked at issues of masculinity have
      been on prostate and/or testicular cancer and have tended to focus upon sexual
      ability and activity, this study identified more sociological issues of concern
      that also present challenges to masculinity and to male identity. Economic
      concerns were identified as being major issues for men, as were their changing
      role vis-a-vis their family, friends and colleagues, and changes to their body
      and to their body image. The findings from this study indicate that cancer
      support services need to be gender sensitive in order to ensure that
      interventions do not undermine masculine values but address men's concerns and
      foster their positive coping strategies.

PMID- 20030701
TI  - The effect of aerobic exercise on treatment-related acute toxicity in men
      receiving radical external beam radiotherapy for localised prostate cancer.
AB  - We retrospectively analysed acute radiation toxicity data for patients who had
      participated in a randomised controlled study in our centre in order to assess
      the impact of aerobic exercise on acute rectal and bladder morbidity during
      treatment. Data from 65 of 66 patients were analysed: 33 allocated into a control
      group (standard advice) and 33 into an exercise group (aerobic walking for 30 min
      at least three times per week) during 4 weeks of external beam radiotherapy; one
      patient in the exercise group withdrew after randomisation before starting
      radiotherapy. There was a trend towards less severe acute rectal toxicity in the
      exercise group with a statistically significant difference in mean toxicity
      scores over the 4 weeks of radiotherapy (P=0.004), with no significant difference
      in bladder toxicity scores between the two groups (P=0.123). The lack of an
      association for severity of bladder toxicity could be attributed to the
      confounding effect of lower urinary tract symptoms from their prostate cancer.
      Keeping active and being asked to adhere to a well-defined exercise schedule
      appears to reduce the severity of rectal toxicity during radiotherapy to the
      prostate.

PMID- 20030702
TI  - The effect of communication skills training on patient outcomes in cancer care: a
      systematic review of the literature.
AB  - The objective of this review was to determine whether communication training for
      healthcare professionals (HCP), including nurses and medical doctors, in cancer
      care improves patient outcomes. Eligible studies with a focus on patient outcomes
      and a controlled or single group pretest-posttest design were identified
      according to Cochrane Collaboration Guidelines. Seven studies, encompassing 10
      papers and involving five randomised controlled trials, were included. Studies
      involved 411 HCP, including a total of 1677 encounters with adult cancer
      patients. Forty-nine papers were excluded, primarily because no patient outcomes
      were reported. Regarding patient satisfaction outcomes, estimated effects in
      favour of communication training ranged from 0.07 (95% CI: -0.30 to 0.44) for
      satisfaction with information and support to 0.70 (95% CI: 0.16 to 1.24) for
      satisfaction with assessment of concerns. No evidence was found for the
      effectiveness of communication training on patient distress outcomes. We
      concluded that the current review reveals inconclusive evidence to prove the
      effectiveness of communication training on patient satisfaction and patient
      distress. More high-quality studies are needed.

PMID- 20030704
TI  - Dying at home: community nurses' views on the impact of informal carers on cancer
      patients' place of death.
AB  - Giving patients with cancer a choice in where they want to die including the
      choice to die at home if they so wish, underpin the recent UK government policies
      and is embedded in the End of Life Care Programme. However, this presents
      increasing challenges for the informal carers particularly with an increasingly
      aging population. Despite the policy initiatives, there remain a persistent
      number of patients with cancer who had chosen to die at home being admitted to
      hospital in the last days and hours of life. A qualitative study using two focus
      group interviews with community nurses (district nurses and community specialist
      palliative care nurses) was undertaken across two primary care trusts in the
      north-west of England. Data were analysed using a thematic analysis approach. The
      results indicated that informal carer burden was a key reason for prompting
      hospital admission. Recommendations for the development of a carer assessment
      tool with appropriate supportive interventions are made.

PMID- 20030706
TI  - Spontaneous mutation parameters for Arabidopsis thaliana measured in the wild.
AB  - Mutations are the ultimate source of genetic diversity and their contributions to
      evolutionary process depend critically on their rate and their effects on traits,
      notably fitness. Mutation rate and mutation effect can be measured simultaneously
      through the use of mutation accumulation lines, and previous mutation
      accumulation studies measuring these parameters have been performed in laboratory
      conditions. However, estimation of mutation parameters for fitness in wild
      populations requires assays in environments where mutations are exposed to
      natural selection and natural environmental variation. Here we quantify mutation
      parameters in both the wild and greenhouse environments using 100 25th generation
      Arabidopsis thaliana mutation accumulation lines. We found significantly greater
      mutational variance and a higher mutation rate for fitness under field conditions
      relative to greenhouse conditions. However, our field estimates were low when
      scaled to natural environmental variation. Many of the mutation accumulation
      lines have increased fitness, counter to the expectation that nearly all
      mutations decrease fitness. A high mutation rate and a low mutational
      contribution to phenotypic variation may explain observed levels of natural
      genetic variation. Our findings indicate that mutation parameters are not fixed,
      but are variables whose values may reflect the specific environment in which
      mutations are tested.

PMID- 20030707
TI  - Recent ecological divergence despite migration in sockeye salmon (Oncorhynchus
      nerka).
AB  - Ecological divergence may result when populations experience different selection
      regimes, but there is considerable discussion about the role of migration at the
      beginning stages of divergence before reproductive isolating mechanisms have
      evolved. However, detection of past migration is difficult in current populations
      and tools to differentiate genetic similarities due to migration versus recent
      common ancestry are only recently available. Using past volcanic eruption times
      as a framework, we combine morphological analyses of traits important to
      reproduction with a coalescent-based genetic analysis of two proximate sockeye
      salmon (Oncorhynchus nerka) populations. We find that this is the most recent
      (approximately 500 years, 100 generations) natural ecological divergence recorded
      in a fish species, and report that this divergence is occurring despite
      migration. Although studies of fish divergence following the retreat of glaciers
      (10,000-15,000 years ago) have contributed extensively to our understanding of
      speciation, the Aniakchak system of sockeye salmon provides a rare example of the
      initial stages of ecological divergence following natural colonization. Our
      results show that even in the face of continued migration, populations may
      diverge in the absence of a physical barrier.

PMID- 20030708
TI  - Extinction rates should not be estimated from molecular phylogenies.
AB  - Molecular phylogenies contain information about the tempo and mode of species
      diversification through time. Because extinction leaves a characteristic
      signature in the shape of molecular phylogenetic trees, many studies have used
      data from extant taxa only to infer extinction rates. This is a promising
      approach for the large number of taxa for which extinction rates cannot be
      estimated from the fossil record. Here, I explore the consequences of violating a
      common assumption made by studies of extinction from phylogenetic data. I show
      that when diversification rates vary among lineages, simple estimators based on
      the birth-death process are unable to recover true extinction rates. This is
      problematic for phylogenetic trees with complete taxon sampling as well as for
      the simpler case of clades with known age and species richness. Given the
      ubiquity of variation in diversification rates among lineages and clades, these
      results suggest that extinction rates should not be estimated in the absence of
      fossil data.

PMID- 20030709
TI  - Prohibitin is expressed in pancreatic beta-cells and protects against oxidative
      and proapoptotic effects of ethanol.
AB  - Pancreatic beta-cell dysfunction is a prerequisite for the development of type 2
      diabetes. Alcoholism is a diabetes risk factor and ethanol increases oxidative
      stress in beta-cells, whereas the mitochondrial chaperone prohibitin (PHB) has
      antioxidant effects in several cell types. In the present study we investigated
      whether PHB is expressed in beta-cells and protects these cells against
      deleterious effects of ethanol, using INS-1E and RINm5F beta-cell lines.
      Endogenous PHB was detected by western blot and immunocytochemistry. Reactive
      oxygen species were determined by 5-(and-6)-chloromethyl-2',7'
      dichlorodihydrofluorescein diacetate fluorescence assay, and mitochondrial
      activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium
      bromide (MTT) reduction, uncoupling protein 2 expression and ATP production. Cell
      death was determined by Hoechst 33342 staining, cleaved caspase-3 levels and flow
      cytometry. PHB was expressed in beta-cells under normal conditions and
      colocalized with Hoechst 33342 in the nucleus and with the mitochondrial probe
      Mitofluor in the perinuclear area. In ethanol-treated cells, MTT reduction and
      ATP production decreased, whereas reactive oxygen species, uncoupling protein 2
      and cleaved caspase-3 levels increased. In addition, flow cytometry analysis
      showed an increase of apoptotic cells. Ethanol treatment increased PHB expression
      and induced PHB translocation from the nucleus to the mitochondria. PHB
      overexpression decreased the apoptotic effects of ethanol, whereas PHB knockdown
      enhanced these effects. The protective effects of endogenous PHB were
      recapitulated by incubation of the cells with recombinant human PHB. Thus, PHB is
      expressed in beta-cells, increases with oxidative stress and protects the cells
      against deleterious effects of ethanol.

PMID- 20030710
TI  - Comparison of functional properties of two fungal antifreeze proteins from
      Antarctomyces psychrotrophicus and Typhula ishikariensis.
AB  - Antifreeze proteins are structurally diverse polypeptides that have thermal
      hysteresis activity and have been discovered in many cold-adapted organisms. Of
      these, fungal antifreeze protein has been purified and partially characterized
      only in a species of psychrophilic basidiomycete, Typhula ishikariensis. Here we
      report a new fungal antifreeze protein from another psychrophile, Antarctomyces
      psychrotrophicus. We examined its biochemical properties and thermal hysteresis
      activity, and compared them with those of the T. ishikariensis antifreeze
      protein. The antifreeze protein from A. psychrotrophicus was purified and
      identified as an extracellular protein of approximately 28 kDa, which halved in
      size following digestion with glycosidase. The A. psychrotrophicus antifreeze
      protein generated bipyramidal ice crystals and exhibited thermal hysteresis
      activity (for example thermal hysteresis = 0.42 degrees C for a 0.48 mM solution)
      similar to that of fish antifreeze proteins, while a unique rugged pattern was
      created on the facets of the ice bipyramid. The thermal hysteresis activity of
      the A. psychrotrophicus antifreeze protein was maximized under alkaline
      conditions, while that of the T. ishikariensis antifreeze protein was greatest
      under acidic conditions. The T. ishikariensis antifreeze protein exhibited a
      bursting ice growth normal to the c-axis of the ice crystal and high thermal
      hysteresis activity (approximately 2 degrees C), as in the case of insect
      hyperactive antifreeze proteins. From these results, we speculate that the A.
      psychrotrophicus antifreeze protein is very different from the T. ishikariensis
      antifreeze protein, and that these two psychrophiles have evolved from different
      genes.

PMID- 20030712
TI  - Identification and molecular characterization of a cyclic-di-GMP effector
      protein, PlzA (BB0733): additional evidence for the existence of a functional
      cyclic-di-GMP regulatory network in the Lyme disease spirochete, Borrelia
      burgdorferi.
AB  - The Borrelia burgdorferi Rrp1 protein is a diguanylate cyclase that controls a
      regulon consisting of approximately 10% of the total genome. Because Rrp1 lacks a
      DNA-binding domain, its regulatory capability is most likely mediated through the
      production of bis-(3'-5')-cyclic dimeric GMP (c-di-GMP). C-di-GMP binds to and
      activates the regulatory activity of proteins that harbor a PilZ domain. The
      occurrence of a PilZ domain within a protein is not in and of itself sufficient
      to convey c-di-GMP binding, as other structural aspects of the protein are
      important in the interaction. In this study, we have assessed the expression and
      c-di-GMP binding ability of the sole PilZ domain-containing protein of B.
      burgdorferi B31, PlzA. PlzA was determined to be upregulated by tick feeding and
      to be expressed during mammalian infection. The gene is highly conserved and
      present in all Borrelia species. Analyses of recombinant PlzA demonstrated its
      ability to bind c-di-GMP and site-directed mutagenesis revealed that this
      interaction is highly specific and dependent on Arg residues contained within the
      PilZ domain. In summary, this study is the first to identify a c-di-GMP effector
      molecule in a spirochete and provides additional evidence for the existence of a
      complete c-di-GMP regulatory network in the Lyme disease spirochete, B.
      burgdorferi.

PMID- 20030713
TI  - Adipophilin protein expression in muscle--a possible protective role against
      insulin resistance.
AB  - Adipophilin is a 50 kDa protein that belongs to the PAT family (perilipin,
      adipophilin, TIP47, S3-12 and OXPAT), which comprises proteins involved in the
      coating of lipid droplets. Little is known about the functional role of
      adipophilin in muscle. Using the C2C12 cell line as a model, we demonstrate that
      palmitic acid-treated cells highly express the adipophilin protein in a dose
      dependent way. Next, we show that oleic acid is a more potent inducer of
      adipophilin protein levels than palmitic acid. Cells treated with oleic acid have
      a higher adipophilin protein expression and higher triglyceride levels but less
      impairment of insulin signaling than cells treated with palmitic acid.
      Additionally, we show that peroxisome proliferator-activated receptor
      (PPAR)alpha, PPARbeta/delta and PPARgamma agonists all increase the expression of
      the adipophilin protein in C2C12 cells. This effect was most pronounced for the
      PPARalpha agonist GW7647. Furthermore, the expression of adipophilin as a 37 kDa
      N-terminally truncated protein is higher in the gastrocnemius than in the
      quadriceps of C57BL/6J mice, especially after an 8-week high-fat diet. The
      expression of adipophilin was higher in the muscle of mice fed a 4-week high-fat
      diet based on olive oil or safflower oil than in mice fed a 4-week high-fat diet
      based on palm oil. After 2 weeks of intervention, plasma glucose, plasma insulin
      and the homeostasis model assessment of insulin resistance index were lower in
      mice fed a 4-week high-fat diet based on olive oil or safflower oil than in mice
      fed a 4-week high-fat diet based on palm oil. Taken together, the results
      obtained in the present study indicate that adipophilin protein expression in
      muscle is involved in maintaining insulin sensitivity.

PMID- 20030714
TI  - Factors controlling the effect of praziquantel on liver fibrosis in Schistosoma
      mansoni-infected patients.
AB  - An association study of a cohort of 177 Sudanese patients infected with
      Schistosoma mansoni [82 (46%) males and 95 (54%) females] was conducted to
      evaluate the factors controlling the regression of liver fibrosis 39 months after
      treatment with praziquantel using ultrasound evaluation. Periportal fibrosis
      (PPF) was regressed in 63 (35.6%) patients, while the disease progressed to
      higher grades in 24 (13.6%) patients. The grade of PPF did not change in 90
      (50.8%) patients. The mean values of portal vein diameter, splenic vein diameter
      and index liver size in subjects in whom PPF regressed after treatment were
      significantly lower than in subjects in whom the disease was progressed
      (P<0.0001, P=0.031 and P=0.003, respectively). The progression of hepatic
      fibrosis in males (15, 8.5%) was greater than that in females (9, 5.1%). Patients
      with regression or progression phenotypes tend to cluster in certain families.
      Our study indicated that regression, progression and stabilization of PPF after
      praziquantel therapy is controlled by gender, age, grade of fibrosis and possibly
      inherited factors.

PMID- 20030715
TI  - MMP-9/TIMP-1 imbalance induced in human dendritic cells by Porphyromonas
      gingivalis.
AB  - Matrix metalloproteinase-9 (MMP-9) cleaves collagen, allowing leukocytes to
      traffic toward the vasculature and the lymphatics. When MMP-9 is unregulated by
      tissue inhibitor of metalloproteinase-1 (TIMP-1), this can lead to tissue
      destruction. Dendritic cells (DCs) infiltrate the oral mucosa increasingly in
      chronic periodontitis, characterized by infection with several pathogens
      including Porphyromonas gingivalis. In this study, human monocyte-derived DCs
      were pulsed with different doses of lipopolysaccharide of P. gingivalis 381 and
      of Escherichia coli type strain 25922, as well as whole live isogenic fimbriae
      deficient mutant strains of P. gingivalis 381. Levels of induction of MMP-9 and
      TIMP-1, as well as interleukin-10 (IL-10), which reportedly inhibits MMP-9
      induction, were measured by several approaches. Our results reveal that
      lipopolysaccharide of P. gingivalis, compared with lipopolysaccharide from E.
      coli type strain 25922, is a relatively potent inducer of MMP-9, but a weak
      inducer of TIMP-1, contributing to a high MMP-9/TIMP-1 ratio.Whole live P.
      gingivalis strain 381, major fimbriae mutant DPG-3 and double mutant MFB were
      potent inducers of MMP-9, but minor fimbriae mutant MFI was not. MMP-9 induction
      was inversely proportional to IL-10 induction. These results suggest that
      lipopolysaccharide and the minor and the major fimbriae of P. gingivalis may play
      distinct roles in induction by DCs of MMP-9, a potent mediator of local tissue
      destruction and leukocyte trafficking.

PMID- 20030716
TI  - Molecular characterization of class 1 integrons in MDR Pseudomonas aeruginosa
      isolated from clinical settings in Iran, Tehran.
AB  - Seven hundred and fifty nonreplicated clinical isolates of Pseudomonas aeruginosa
      were collected from five hospitals during March 2007 to May 2009. Forty-one
      isolates (5.46%) were characterized as multidrug-resistant P. aeruginosa (MDRPA).
      PCR assays were used to detect class 1 integrons. Amplifications of internal
      variable regions (IVRs) of class 1 integrons revealed three different arrays
      (0.8, 1.3, and 1.7 kb) with different distributions in clinical isolates. The
      amplified IVRs were sequenced and three gene cassette arrays including aadB (0.8
      kb), aadA6-orfD (1.3 kb), and bla(OXA10)-aacA4 (1.7 kb) were identified. In
      conclusion, we confirmed the high prevalence of class 1 integons with limited
      diversity of gene cassette arrays in MDRPA clinical isolates found from five
      hospitals. This is the first report showing gene cassette contents of class 1
      integrons in P. aeruginosa isolates in Iran.

PMID- 20030717
TI  - Effect of environment on the abundance and activity of the nematophagous fungus
      Hirsutella minnesotensis in soil.
AB  - Environmental factors greatly affect the activity of soil microorganisms.
      However, not enough is known about how the environment affects the abundance and
      activity of many beneficial microorganisms after they are released into soil.
      Hirsutella minnesotensis is an important fungal parasite of nematodes and has
      shown great potential in nematode control. The objective of this study was to
      measure the effects of environmental factors on the abundance and activity of H.
      minnesotensis in soil. Fungal mycelium was mixed with dry soil (1% wet weight per
      dryweight) and placed into 50-mL plastic tubes. Soil temperature ranged from 5 to
      30 degrees C; soil water content ranged from 6% to 22%; and the soil was
      supplemented with 0-70% of fine soil particles (silt and clay) or sand. After 24
      days, fungal abundance was quantified by real-time PCR and its activity was
      inferred from the numbers of second-stage juveniles (J2) parasitized. The amount
      of H. minnesotensis DNA g(-1) soil and the percentage of J2 parasitized by H.
      minnesotensis were higher with lower soil temperature and water content, and
      higher fine particle content, demonstrating that H. minnesotensis has a greater
      potential to multiply and control pest nematodes in cooler, drier and heavier
      soils.

PMID- 20030719
TI  - Reduction of accumulated volatile fatty acids by an acetate-degrading enrichment
      culture.
AB  - The effects of the addition of an acetate-degrading enrichment culture to an
      anaerobic digester with a stagnating biogas production were investigated.
      Initially, a thermophilic batch-operated lab-scale digester was inoculated with
      the diluted fermenter sludge of a biogas plant, and process parameters including
      the concentration of volatile fatty acids (VFAs) and gases in the headspace were
      measured. After a phase of high gas production, a stagnation of biogas production
      followed for a further 30 days. An acetate enrichment culture was added 34 days
      after the commencement of the experiment and this resulted in a sharp decrease in
      the concentrations of accumulated VFAs and an increase in total biogas and CH(4)
      production. An archaeon with a sequence similarity of 98% to Methanosarcina sp.
      and the ability to degrade acetic acid was introduced with the enrichment culture
      and is proposed to have been the driving factor for the changes that occurred
      within a few days to the process.

PMID- 20030718
TI  - Identification of a novel ABC transporter required for desiccation tolerance, and
      biofilm formation in Rhizobium leguminosarum bv. viciae 3841.
AB  - Rhizobium leguminosarum is a soil bacterium with the ability to form nitrogen
      fixing nodules on the roots of leguminous plants. Soil-dwelling, free-living R.
      leguminosarum often encounters desiccation stress, which impacts its survival
      within the soil. The mechanisms by which soil bacteria resist the effects of
      desiccation stress have been described. However, the role of the cell envelope in
      the desiccation tolerance mechanisms of rhizobia is relatively uncharacterized.
      Using a transposon mutagenesis approach, a mutant of R. leguminosarum bv. viciae
      was isolated that was highly sensitive to desiccation. The mutation is located in
      the ATP-binding protein of an uncharacterized ATP-binding cassette transporter
      operon (RL2975-RL2977). Exopolysaccharide accumulation was significantly lower in
      the mutant and the decrease in desiccation tolerance was attributed to the
      decreased accumulation of exopolysaccharide. In addition to desiccation
      sensitivity, the mutant was severely impaired in biofilm formation, an important
      adaptation used by soil bacteria for survival. This work has identified a novel
      transporter required for physiological traits that are important for the survival
      of R. leguminosarum in the rhizosphere environment.

PMID- 20030720
TI  - Genetic analysis of CTX prophages with special reference to ctxB and rstR alleles
      of Vibrio cholerae O139 strains isolated from Kolkata over a decade.
AB  - Chronological analysis of 125 Vibrio cholerae O139 strains isolated during 1993
      2005 in Kolkata revealed the prevalence of two new genotypes of cholera toxin
      (CT) and novel combinations of ctxB and rstR alleles resulting in variant CTX
      prophages. One of the new genotypes of ctxB, which first appeared in 1996 with
      the re-emerged V. cholerae O139 strains that had CTX Calcutta phage, was
      designated as genotype 4. In 1998, another new genotype, designated as genotype
      5, was detected that prevailed mostly in CTX phages with El Tor rstR. The
      prototype El Tor CTX phage with genotype 3 gradually disappeared in O139, and
      since 2002 the predominant CTX prophages in O139 are Calcutta phages with
      genotype 4 and El Tor phages with genotype 5. Results showed that V. cholerae
      O139 strains of Kolkata, isolated over a decade, harboured CTX prophages in the
      large chromosome having no RS1 downstream of CTX prophage. During the course of
      its intermittent incidence over a decade, five types of O139 strains were
      detected based on CT genotypes. Such abrupt genetic changes in O139 strains might
      not favour its continued prevalence in human cases in Kolkata, India.

PMID- 20030721
TI  - Skn1 and Ipt1 negatively regulate autophagy in Saccharomyces cerevisiae.
AB  - We demonstrated that a yeast deletion mutant in IPT1 and SKN1, encoding proteins
      involved in the biosynthesis of mannosyldiinositolphosphoryl ceramides, is
      characterized by increased autophagy and DNA fragmentation upon nitrogen (N)
      starvation as compared with the single deletion mutants or wild type (WT).
      Apoptotic features were not significantly different between single and double
      deletion mutants upon N starvation, pointing to increased autophagy in the double
      Deltaipt1 Deltaskn1 deletion mutant independent of apoptosis. We observed
      increased basal levels of phytosphingosine in membranes of the double Deltaipt1
      Deltaskn1 deletion mutant as compared with the single deletion mutants or WT.
      These data point to a negative regulation of autophagy by both Ipt1 and Skn1 in
      yeast, with a putative involvement of phytosphingosine in this process.

PMID- 20030722
TI  - Effect of the association of reduced glutathione and ciprofloxacin on the
      antimicrobial activity in Staphylococcus aureus.
AB  - We report the effect of glutathione and the role of reactive oxygen species
      (ROS), assayed by a nitro blue tetrazolium reaction, on the antibacterial action
      of ciprofloxacin, gentamicin and chloramphenicol in Staphylococcus aureus 22
      resistant to ciprofloxacin and gentamicin, and in S. aureus ATCC 29213 sensitive
      to the above three antibiotics. The association of glutathione with ciprofloxacin
      or gentamicin significantly reduced the value of the minimum inhibitory
      concentration (MIC) in resistant S. aureus 22, measured using the macrodilution
      method, with a concomitant increase of intracellular ROS and a decrease of
      extracellular ROS. However, glutathione did not induce modifications in MIC or
      ROS generated by chloramphenicol. Furthermore, in the sensitive S. aureus ATCC
      29213, the association of glutathione with ciprofloxacin, gentamicin or
      chloramphenicol did not induce any significant variations of MIC or ROS. There
      was a correlation between the stimulus of intracellular ROS and the decrease of
      MIC caused by exogenous glutathione. According to the results obtained, it is
      possible to modify the sensitivity of resistant strains of S. aureus by the
      addition of exogenous glutathione.

PMID- 20030723
TI  - Evaluation of multiple-locus variable number of tandem-repeats analysis (MLVA) as
      a method for identification of clonal groups among enteropathogenic,
      enterohaemorrhagic and avirulent Escherichia coli O26 strains.
AB  - A published multiple-locus variable number of tandem-repeats analysis (MLVA)
      scheme was compared with pulsed-field gel electrophoresis (PFGE) for genotyping
      of 62 Escherichia coli O26 strains from humans, animals and food. The strains
      were isolated between 1947 and 2006 in eight countries on three continents and
      divided into 23 enterohaemorrhagic E. coli (EHEC), 33 enteropathogenic E. coli
      (EPEC), one enterotoxigenic E. coli (ETEC) and five avirulent strains. ETEC and
      avirulent E. coli serotyped as O26:H32. EHEC and EPEC O26 strains shared
      flagellar type H11 and the eae-beta gene, and divided into two clonal lineages by
      their arcA gene sequence and fermentation of rhamnose and dulcitol. The
      rhamnose/dulcitol-nonfermenting (RDF-), 'arcA allele 1' type comprised 22 EHEC
      and 15 EPEC strains. The rhamnose/dulcitol-fermenting (RDF+), 'arcA allele 2'
      type encompassed 17 EPEC and one EHEC strain. PFGE typing of the 62 O26 strains
      revealed 54 distinct patterns, whereas 29 profiles were obtained by MLVA. Like
      PFGE, MLVA divided RDF- and RDF+ O26:[H11] strains into two distinct clusters of
      related strains. The O26:H32 strains formed a separate PFGE cluster and two
      clusters by MLVA. MLVA was found as suitable, but more rapid and easier to
      standardize than PFGE for identifying genetically related E. coli O26 strains.

PMID- 20030725
TI  - Transcriptional profile of the Shigella flexneri response to an alkaloid:
      berberine.
AB  - Berberine, a natural isoquinoline alkaloid found in many medicinal herbs, has
      been shown to be active against a variety of microbial infections. To examine the
      potential effects of berberine on Shigella flexneri, a whole-genome DNA
      microarray was constructed and a transcriptome analysis of the cellular responses
      of S. flexneri when exposed to berberine chloride (BC) was performed. Our data
      revealed that BC upregulated a group of genes involved in DNA replication, repair
      and division. Intriguingly, the expression of many genes related to cell envelope
      biogenesis was increased. In addition, many genes involved in cell secretion,
      nucleotide metabolism, translation, fatty acid metabolism and the virulence
      system were also induced by the drug. However, more genes from the functional
      classes of carbohydrate metabolism, energy production and conversion as well as
      amino acid metabolism were significantly repressed than were induced. These
      results provide a comprehensive view of the changes in gene expression when S.
      flexneri was exposed to BC, and shed light on its complicated effects on this
      pathogen.

PMID- 20030724
TI  - Phosphatidylcholine levels of peanut-nodulating Bradyrhizobium sp. SEMIA 6144
      affect cell size and motility.
AB  - Phosphatidylcholine, the major phospholipid in eukaryotes, is found in rhizobia
      and in many other bacteria interacting with eukaryotic hosts. Phosphatidylcholine
      has been shown to be required for a successful interaction of Bradyrhizobium
      japonicum USDA 110 with soybean roots. Our aim was to study the role of bacterial
      phosphatidylcholine in the Bradyrhizobium-peanut (Arachis hypogaea) symbiosis.
      Phospholipid N-methyltransferase (Pmt) and minor phosphatidylcholine synthase
      (Pcs) activities were detected in crude extracts of the peanut-nodulating strain
      Bradyrhizobium sp. SEMIA 6144. Our results suggest that phosphatidylcholine
      formation in Bradyrhizobium sp. SEMIA 6144 is mainly due to the phospholipid
      methylation pathway. Southern blot analysis using pmt- and pcs-probes of B.
      japonicum USDA 110 revealed a pcs and multiple pmt homologues in Bradyrhizobium
      sp. SEMIA 6144. A pmtA knockout mutant was constructed in Bradyrhizobium sp.
      SEMIA 6144 that showed a 50% decrease in the phosphatidylcholine content in
      comparison with the wild-type strain. The mutant was severely affected in
      motility and cell size, but formed wild-type-like nodules on its host plant.
      However, in coinoculation experiments, the pmtA-deficient mutant was less
      competitive than the wild type, suggesting that wild-type levels of
      phosphatidylcholine are required for full competitivity of Bradyrhizobium in
      symbiosis with peanut plants.

PMID- 20030726
TI  - Genomic differences between Actinobacillus pleuropneumoniae serotypes 1 and 3 and
      the diversity distribution among 15 serotypes.
AB  - The limited information on the genetic differences among the 15 currently known
      serotypes of Actinobacillus pleuropneumoniae has significantly hampered the
      development of typing-based diagnostic methods and multivalent vaccines. In this
      study, we compared the genomic differences between A. pleuropneumoniae strains
      CVCC259 (serotype 1) and CVCC261 (serotype 3) by representational difference
      analysis. Of the eight differential DNA sequences in the CVCC259 strain and 11
      differential DNA sequences in the CVCC261 strain that we identified, seven
      represent known virulent genes, 10 encode putative proteins, and two encode
      hypothetical proteins. We also investigated the distribution of these 19
      sequences among the 15 serotypes, and each serotype showed a different
      distribution pattern. The autotransporter adhesin occurred as a novel putative
      virulence factor in serotypes 1, 5, 7, 8, 9, and 11. Notably, the presence of wzm
      and wzt in serotypes 1, 9, and 11 and the diverse distribution of wzz and wzy in
      the other serotypes suggest the presence of different O-antigen biosynthesis
      pathways among serotypes. The information on the differential distribution of
      these DNA sequences in the 15 serotypes of A. pleuropneumoniae may contribute to
      future research on the pathogenic mechanisms of different serotypes, typing-based
      diagnosis methods, and multivalent vaccines.

PMID- 20030727
TI  - Characterization of an SXT variant Vibrio cholerae O1 Ogawa isolated from a
      patient in Trivandrum, India.
AB  - The emerging multiple drug resistance in bacterial pathogens is complicating the
      treatment of diseases and hence is a major public health concern. In the present
      study, Vibrio cholerae O1 El Tor Ogawa isolated from a patient was examined for
      antibiotic susceptibility pattern, presence of SXT and its transmissibility,
      associated drug resistance genes and variation in the int gene and the attP
      attachment site of SXT. The strain showed resistance to ampicillin, polymixin B,
      co-trimoxazole, trimethoprim, streptomycin, spectinomycin, furazolidone,
      tetracycline, ciprofloxacin and nalidixic acid. The sequencing of int, the SXT
      specific integrase and attP attachment site indicated that it possessed a variant
      of SXT with trimethoprim (dfrA1), sulphamethoxazole (sul2) and streptomycin
      (strB) resistance genes. Its mobile nature was demonstrated by conjugation with
      rifampicin-resistant Escherichia coli. The emergence of such an isolate should be
      closely monitored because it will improve our understanding of the evolution of
      the multidrug resistance phenotype.

PMID- 20030728
TI  - The type IV secretion system affects the expression of Omp25/Omp31 and the outer
      membrane properties of Brucella melitensis.
AB  - The type IV secretion system (T4SS) contributes to Brucella intracellular
      survival through its effector proteins. Comparative proteomic analysis showed
      that intracellular survival proteins are expressed differentially in a virB
      mutant. Interestingly, several outer membrane proteins (OMPs) are also
      differentially expressed, implying that T4SS might affect the OM properties of
      Brucella. To further evaluate the impact of T4SS on OM, in the present study, the
      OM proteomes were isolated and compared. Many more products of OMPs, particularly
      different products of the Omp25/Omp31 family, were found to be altered in the
      virB mutant. The transcription profiles of Omp25/Omp31 were different from those
      of their protein products, implying their regulation by virB at both
      transcriptional and post-transcriptional levels. The virB mutant aggregates at a
      high cell density and produces exopolysaccharide, a phenotype resembling that of
      the vjbR mutant. The virB mutant showed increased sensitivity to polymyxin B and
      decreased survival under oxidative, high-salt and high-osmolarity stresses,
      indicating drastic membrane alterations. These results indicated that in addition
      to being an effector protein secretion system, T4SS affects OM properties that
      might be important for the adaptation of Brucella to both in vitro and in vivo
      hostile environments.

PMID- 20030729
TI  - The antibacterial mode of action of allitridi for its potential use as a
      therapeutic agent against Helicobacter pylori infection.
AB  - Eradication of Helicobacter pylori with traditional therapy often fails in
      clinical treatment. As a result, a novel efficacious therapeutic agent is
      strongly needed. Allitridi, a proprietary garlic derivative, has been
      successfully used to treat both systemic fungal and bacterial infections in
      China. Our previous study has shown a dose-dependent inhibitory effect of
      allitridi on H. pylori growth. However, the antibacterial mode of action of
      allitridi is still unclear. Proteomic analysis was used to study the global
      protein alterations induced by allitridi. A total of 21 protein spots were
      identified to be differentially expressed. Our results indicated that the
      bacteriostatic mechanism of allitridi in H. pylori can be attributed to its
      multitarget inhibitory effects in energy metabolism and biosynthesis including
      amino acid biosynthesis, protein synthesis, mRNA synthesis and fatty acid
      biosynthesis. Allitridi can also disturb the expression of antioxidant proteins
      and decrease the production of virulence factors. Western blot analysis showed
      that allitridi at subinhibitory concentrations can potently suppress the
      production of CagA and VacA. Our investigations on the antibacterial mode of
      action of allitridi provide an insight into the potential use of allitridi as a
      therapeutic agent against H. pylori infection.

PMID- 20030730
TI  - Hydrocarbon utilization within a diesel-degrading bacterial consortium.
AB  - Diesel fuel is a common environmental pollutant comprised of a large number of
      both aromatic and aliphatic hydrocarbons. The microbial degradation of individual
      hydrocarbons has been well characterized, however, the community dynamics within
      a system degrading a complex pollutant such as diesel fuel are still poorly
      understood. The growth capabilities of a diesel-degrading consortium, along with
      organisms isolated from a contaminated site, were investigated using molecular
      profiling, isolation, and physiological methods using 10 of the fuel's most
      abundant constituents as sole carbon sources. The results indicated that the
      degradation of the fuel's constituents may be shared among the diverse microbial
      community. Some organisms were capable of growth on the majority of the
      hydrocarbons tested, whereas others seemed specialized to only a few of the
      substrates.

PMID- 20030731
TI  - Broad-spectrum beta-lactamases among Enterobacteriaceae of animal origin:
      molecular aspects, mobility and impact on public health.
AB  - Broad-spectrum beta-lactamase genes (coding for extended-spectrum beta-lactamases
      and AmpC beta-lactamases) have been frequently demonstrated in the microbiota of
      food-producing animals. This may pose a human health hazard as these genes may be
      present in zoonotic bacteria, which would cause a direct problem. They can also
      be present in commensals, which may act as a reservoir of resistance genes for
      pathogens causing disease both in humans and in animals. Broad-spectrum beta
      lactamase genes are frequently located on mobile genetic elements, such as
      plasmids, transposons and integrons, which often also carry additional resistance
      genes. This could limit treatment options for infections caused by broad-spectrum
      beta-lactam-resistant microorganisms. This review addresses the growing burden of
      broad-spectrum beta-lactam resistance among Enterobacteriaceae isolated from
      food, companion and wild animals worldwide. To explore the human health hazard,
      the diversity of broad-spectrum beta-lactamases among Enterobacteriaceae derived
      from animals is compared with respect to their presence in human bacteria.
      Furthermore, the possibilities of the exchange of genes encoding broad-spectrum
      beta-lactamases - including the exchange of the transposons and plasmids that
      serve as vehicles for these genes - between different ecosystems (human and
      animal) are discussed.

PMID- 20030732
TI  - Extracellular signals that define distinct and coexisting cell fates in Bacillus
      subtilis.
AB  - The soil-dwelling bacterium Bacillus subtilis differentiates into distinct
      subpopulations of specialized cells that coexist within highly structured
      communities. The coordination and interplay between these cell types requires
      extensive extracellular communication driven mostly by sensing self-generated
      secreted signals. These extracellular signals activate a set of sensor kinases,
      which respond by phosphorylating three major regulatory proteins, Spo0A, DegU and
      ComA. Each phosphorylated regulator triggers a specific differentiation program
      while at the same time repressing other differentiation programs. This allows a
      cell to differentiate in response to a specific cue, even in the presence of
      other, possibly conflicting, signals. The sensor kinases involved respond to an
      eclectic group of extracellular signals, such as quorum-sensing molecules,
      natural products, temperature, pH or scarcity of nutrients. This article reviews
      the cascades of cell differentiation pathways that are triggered by sensing
      extracellular signals. We also present a tentative developmental model in which
      the diverse cell types sequentially differentiate to achieve the proper
      development of the bacterial community.

PMID- 20030733
TI  - From the editor.

PMID- 20030734
TI  - Multiple effects of amprenavir against Candida albicans.
AB  - Secreted aspartyl peptidases (Saps) are virulence attributes produced by Candida
      albicans that participate in multiple aspects of the fungal biology and
      pathogenesis. In the present paper, we have shown that amprenavir, a peptidase
      inhibitor used in HIV chemotherapy, inhibited Sap2 and growth of C. albicans and
      also promoted ultrastructural alterations. Esterase activity, sterol content,
      biofilm formation and the expression of surface mannose- and sialic acid-rich
      glycoconjugates were also reduced by amprenavir.

PMID- 20030735
TI  - Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline.
AB  - Oxymetazoline and xylometazoline are both used as nasal mucosa decongesting alpha
      adrenoceptor agonists during a common cold. However, it is largely unknown which
      of the six alpha-adrenoceptor subtypes are actually present in human nasal
      mucosa, which are activated by the two alpha-adrenoceptor agonists and to what
      extent. Therefore, mRNA expression in human nasal mucosa of the six alpha
      adrenoceptor subtypes was studied. Furthermore, the affinity and potency of the
      imidazolines oxymetazoline and xylometazoline at these alpha-adrenoceptor
      subtypes were examined in transfected HEK293 cells. The rank order of mRNA levels
      of alpha-adrenoceptor subtypes in human nasal mucosa was: alpha(2A) > alpha(1A)
      >= alpha(2B) > alpha(1D) >= alpha(2C) >> alpha(1B) . Oxymetazoline and
      xylometazoline exhibited in radioligand competition studies higher affinities
      than the catecholamines adrenaline and noradrenaline at most alpha-adrenoceptor
      subtypes. Compared to xylometazoline, oxymetazoline exhibited a significantly
      higher affinity at alpha(1A) - but a lower affinity at alpha(2B) -adrenoceptors.
      In functional studies in which adrenoceptor-mediated Ca(2+) signals were
      measured, both, oxymetazoline and xylometazoline behaved at alpha(2B) 
      adrenoceptors as full agonists but oxymetazoline was significantly more potent
      than xylometazoline. Furthermore, oxymetazoline was also a partial agonist at
      alpha(1A) -adrenoceptors; however, its potency was relatively low and it was much
      lower than its affinity. The higher potency at alpha(2B) -adrenoceptors, i.e. at
      receptors highly expressed at the mRNA level in human nasal mucosa, could
      eventually explain why in nasal decongestants oxymetazoline can be used in lower
      concentrations than xylometazoline.

PMID- 20030736
TI  - Hepatic effects of flunixin-meglumin in LPS-induced sepsis.
AB  - The aim of this study was to evaluate the actions of the non-steroidal anti
      inflammatory drug flunixin-meglumin (FM) on the changes caused by
      lipopolysaccharide (LPS)-induced sepsis in the rat liver. Eight groups of five
      adult male Wistar rats were analysed: (1) saline injected (controls), (2) FM
      treated with 1.1 mg/kg, (3) FM treated with 2.2 mg/kg, (4) LPS-injected (10
      mg/kg), (5) LPS-injected with 1.1 mg/kg FM pretreatment, (6) LPS-injected with
      2.2 mg/kg FM pretreatment, (7) LPS-injected with 1.1 mg/kg FM post-treatment and
      (8) LPS-injected with 2.2 mg/kg FM post-treatment. All drugs were
      intraperitoneally injected. The following parameters were evaluated: plasma
      levels of hepatic enzymes and urea, hepatic histological characteristics,
      antioxidant enzymes and several metabolic fluxes. The latter comprised
      gluconeogenesis, ureagenesis and oxygen consumption. Liver damage in LPS-induced
      sepsis was characterized by histological changes, increased plasma levels of
      alanine aminotransferase and aspartate aminotransferase (P < 0.001) and
      diminished gluconeogenesis (P < 0.001) and ureagenesis (P < 0.01). LPS also
      induced oxidative stress as evidenced by increased catalase (P < 0.05) and
      superoxide dismutase activities and enhanced lipid peroxidation (P < 0.001).
      Pretreatment of the animals with FM minimized the histological changes and
      normalized, in part, all enzymatic activities. Pretreatment of the animals with
      FM also normalized gluconeogenesis and partly restored ureagenesis (P < 0.05).
      These and other results show that LPS-induced sepsis may lead to severe liver
      damage, affecting both structure and function. Treatment with FM can be used to
      avoid this damage. The antioxidant properties of FM can be, partly at least,
      responsible for this protective action.

PMID- 20030737
TI  - Effects of trimetazidine, a partial inhibitor of fatty acid oxidation, on
      ventricular function and survival after myocardial infarction and reperfusion in
      the rat.
AB  - Trimetazidine (TMZ), a partial inhibitor of fatty acid oxidation, has been
      effective in treating chronic angina, but its effects on the development of post
      myocardial infarction (MI) left ventricular remodeling are not defined. In this
      study, we tested whether chronic pre-MI administration of TMZ would be beneficial
      during and after acute MI. Two-hundred male Wistar rats were studied in four
      groups: sham + TMZ diet (n = 20), sham + control diet (n = 20), MI + TMZ diet (n
      = 80), and MI + control diet (n = 80) splitted into one short-term and one long
      term experiments. Sham surgery consisted of a thoracotomy without coronary
      ligation. MI was induced by coronary occlusion followed by reperfusion. Left
      ventricle (LV) function and remodeling were assessed by serial echocardiography
      throughout a 24-week post-MI period. LV remodeling was also assessed by
      quantitative histological analysis of post-MI scar formation at 24 weeks post-MI.
      During the short-term experiment, 10/80 rats died after MI, with no difference
      between groups (MI + control = 7/40, MI + TMZ = 3/40, P = 0.3). In the long-term
      experiment, the deaths occurred irregularly over the 24 weeks with no difference
      between groups (MI + control = 16% mortality, MI + TMZ = 17%, P = 0.8). There was
      no difference between groups as regard to LV ejection fraction (MI + control = 36
      +/- 13%, MI + TMZ = 35 +/- 13%, P = 0.6). In this experimental model, TMZ had no
      effects on the post-MI occurrence of LV dysfunction or remodeling. Further
      investigations are warranted to assess whether the partial inhibition of fatty
      acid oxidation may limit the ability of the heart to respond to acute severe
      stress.

PMID- 20030738
TI  - Animal models of neuropathic pain.
AB  - Animal models are pivotal for understanding the mechanism of neuropathic pain and
      development of effective therapy for its optimal management. A battery of
      neuropathic pain models has been developed to simulate the clinical pain
      conditions with diverse etiology. The present review exhaustively discusses the
      methodology, behavioral alterations, limitations, and advantages of about 40
      different animal models of neuropathic pain along with their modifications.
      Development of these models has contributed immensely in understanding the
      chronic pain and underlying peripheral as well as central pathogenic mechanisms.
      Furthermore, research has resulted in the development of new therapeutic agents
      for neuropathic pain management, and the preclinical data obtained using these
      animal models have been successively translated to effective pain management in
      clinical setup also. As each animal model has been created with specific
      methodology and results tend to vary largely with the slight changes related to
      methodology, therefore, it is essential that data from different models should be
      reported and interpreted in the context of the specific pain model.

PMID- 20030739
TI  - The effect of insulin in combination with selenium on blood glucose and GLUT4
      expression in the cardiac muscle of streptozotocin-induced diabetic rats.
AB  - We evaluated the effect of a combination of low doses of insulin (1 U/kg/day) and
      selenium (180 microg/kg/day) on general physiological parameters and the level of
      glucose transporter (GLUT4) in the cardiac muscle of streptozotocin-induced
      diabetic rats. Diabetic rats were treated with insulin, selenium and a
      combination of insulin and selenium for 4 weeks. The levels of blood glucose and
      hemoglobin A1c were estimated; the level of the GLUT4 in the cardiac muscle was
      examined by immunoblotting and immunohistochemistry. Insulin in combination with
      selenium could significantly lower blood glucose and HbA1c levels and could
      restore disturbances in GLUT4 level in the cardiac muscle. The treatment with
      insulin was only partially effective in the restoration of diabetic alterations.
      We conclude that there was cooperation between insulin and selenium, and that the
      treatment of diabetic rats with combined doses of insulin and selenium was
      effective in the control of blood glucose and correction of altered GLUT4
      distribution in diabetic rat hearts.

PMID- 20030741
TI  - Rapidly metastatic carcinoma in lupo in a patient with lupus vulgaris for more
      than 50 years.
AB  - According to current statistics of the WHO, tuberculosis is the infectious
      disease that causes the most deaths worldwide. Its most common cutaneous
      manifestation is lupus vulgaris which is seldom diagnosed today. A 69-year old
      immunocompetent woman complained of a partly elevated, partly sclerotic plaque on
      her left thigh which had been present for more than 55 years before slowly
      becoming ulcerated. After biopsy and subsequent excision of the 13 cm ulcer, the
      diagnosis of carcinoma in lupo with lymph node metastasis was made. Cutaneous and
      additional nodal metastases appeared rapidly. Tuberculostatic therapy was
      initiated. Despite systemic chemotherapy the tumor subsequently progressed and
      the patient died of metastatic carcinoma in lupo 15 months after the initial
      diagnosis. Early diagnosis and treatment of lupus vulgaris might have prevented
      the development of carcinoma in lupo and ensuing metastatic death of the patient.

PMID- 20030742
TI  - Expert guideline on the use of porcine collagen in aesthetic medicine.

PMID- 20030743
TI  - The Brief Pain Inventory and its "pain at its worst in the last 24 hours" item:
      clinical trial endpoint considerations.
AB  - CONTEXT: In 2006, the United States Food and Drug Administration (FDA) released a
      draft Guidance for Industry on the use of patient-reported outcomes (PRO)
      Measures in Medical Product Development to Support Labeling Claims. This draft
      guidance outlines psychometric aspects that should be considered when designing a
      PRO measure, including conceptual framework, content validity, construct
      validity, reliability, and the ability to detect clinically meaningful score
      changes. When finalized, it may provide a blueprint for evaluations of PRO
      measures that can be considered by sponsors and investigators involved in PRO
      research and drug registration trials. OBJECTIVE: In this review we examine the
      short form of the Brief Pain Inventory (BPI) and particularly the "pain at its
      worst in the last 24 hours" item in the context of the FDA draft guidance, to
      assess its utility in clinical trials that include pain as a PRO endpoint.
      RESULTS AND CONCLUSIONS: After a systematic evaluation of the psychometric
      aspects of the BPI, we conclude that the BPI and its "pain at its worst in the
      last 24 hours" item generically satisfy most key recommendations outlined in the
      draft guidance for assessing a pain-reduction treatment effect. Nonetheless, when
      the BPI is being considered for assessment of pain endpoints in a registration
      trial, sponsors and investigators should consult with the appropriate FDA
      division early during research design to discuss whether there is sufficient
      precedent to use the instrument in the population of interest or whether
      additional evaluations of measurement properties are advisable.

PMID- 20030744
TI  - A new muscle pain detection device to diagnose muscles as a source of back and/or
      neck pain.
AB  - BACKGROUND: Trigger point (TrPs) identification has become the mainstay of
      diagnosis for the treatment of Myofascial Pain Syndrome; however, manual pressure
      (MP) to identify TrPs by determining low-pressure pain threshold has low
      interrater reliability and may lack validity since it is done on inactive
      muscles. To elicit contractions and mimic an active muscle or movement that
      "causes" pain, a Muscle Pain Detection Device (MPDD) has been developed. A
      selected muscle is stimulated and painful muscles are precisely detected,
      allowing distinctions between primary and referred muscle pain as well as
      distinguishing other functional muscle pain thought to cause MPS. METHODS: An IRB
      approved randomized controlled study is presented of MP (20 patients) control vs
      MPDD (20 patients) to identify which muscle(s) was the source of pain in subjects
      presenting to the NYU Pain Management Center with a minimum 3 months history of
      back pain. Patients were unaware of their diagnostic method. Subjects were
      injected in 1-3 sites identified via MP or MPDD by a separate, blinded physician.
      Prior to, and following treatment at one week and one month, the patients were
      administered Oswestry and visual analog scale pain questionnaires by a blinded
      evaluator, and their range of motion was measured by a blinded physical
      therapist. RESULTS: The MPDD group reported significantly larger improvements in
      pain, mood and Oswestry scores compared with the control (P < 0.05). Moreover,
      the MPDD group reported 82.5% pain relief at 1 month, compared with 53.2% in the
      control (P < 0.001). The range of motion measurements failed to reveal any
      significant difference between the groups. CONCLUSIONS: Using the MPDD appears to
      be more valid and potentially more reliable than palpation to identify muscles
      causing regional pain that could benefit from injections.

PMID- 20030745
TI  - Cooled radiofrequency (RF) of L5 dorsal ramus for RF denervation of the
      sacroiliac joint: technical report.
AB  - BACKGROUND AND OBJECTIVES: The sacroiliac joint is a common source of chronic low
      back pain. We recently described the use of cooled radiofrequency (RF) electrodes
      for performing lateral branch neurotomy to treat sacroiliac joint pain. The
      procedure involves lesioning the lateral branches of the posterior primary rami
      at S1-S3, and the L5 dorsal ramus (L5DR). While the cooled RF electrode has been
      adopted as a means for lesioning the lateral branches, conventional RF electrodes
      are used to lesion the L5DR. The objective of this technical report is to
      evaluate the acute safety of denervating the L5DR using cooled RF electrode.
      METHODS: Electronic chart review was conducted on 100 consecutive RF procedures.
      Data collected included age, sex, years of pain, body mass index, post-procedural
      pain, numbness, weakness, and other complications. RESULTS: Of 100 procedures 82
      were completed using cooled electrode for sacral lateral branches and L5DR. Of
      the 82 procedures completed using cooled RF to L5DR, 24 were reported to be of
      high difficulty and 19 with poor visualization (bowel gas). There were no major
      complications related to the procedure. Four patients reported increased pain:
      two from the conventional RF of L5DR group and two from the cooled RF group. All
      of the pains were transient and returned to the baseline within 6 weeks. There
      were two patients experiencing localized numbness over the upper medial quadrant
      of the buttock, both in cooled RF group. There was no reported weakness of the
      lower extremity. Two patients complained of increased lower back pain and two of
      prolonged itching. CONCLUSIONS: This review demonstrates the acute safety of
      using cooled RF for L5DR denervation with no report of significant or unusual
      patient complications. To establish frequency of complication associated with the
      treatment, a larger registry is required.

PMID- 20030746
TI  - WITHDRAWN: TRANSIENT TACHYPNEA OF THE NEWBORN: A PREDICTIVE FACTOR FOR PROLONGED
      TACHYPNEA.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 20030747
TI  - Activity, inactivity and quality of life among Lebanese adolescents.
AB  - BACKGROUND: The aim of the present study was to investigate recent overweight and
      obesity prevalence rates for Lebanese adolescents, and to examine differences in
      physical activity, screen time (sum of time spent in front of TV, computer, and
      videogames), and health-related quality of life (HRQOL) for the first time among
      normal, overweight, and obese adolescents. METHODS: One thousand Lebanese
      adolescents (14-18 years old) from nine schools participated in the study.
      Height, weight, physical activity, screen time, and HRQOL variables were assessed
      using validated self-report questionnaires. RESULTS: A total of 7.8% of boys and
      1.75% of girls were obese, and 22.5% of boys and 12.47% of girls were overweight.
      Normal-weight boys reported higher physical activity scores at health clubs than
      obese boys. Normal-weight girls reported higher leisure time and total physical
      activity scores than obese girls. In the normal-weight group, boys reported
      higher total screen time than girls. Normal-weight boys reported higher physical
      functioning scores than their obese peers. Normal-weight girls reported higher
      physical functioning and average HRQOL scores than obese girls. Normal-weight and
      overweight boys reported higher average HRQOL scores than girls. CONCLUSION: The
      present study is the first to provide data on physical activity, screen time, and
      HRQOL among Lebanese adolescents. Despite the need for further research, all
      those concerned with the pediatric population are urged to develop and implement
      effective strategies to increase physical activity and improve HRQOL among
      adolescents based on the present findings.

PMID- 20030748
TI  - Comprehensive genetic analysis of overlapping syndromes of RAS/RAF/MEK/ERK
      pathway.
AB  - BACKGROUND: Germline mutations in several members of RAS/RAF/MEK/ERK pathway
      cause clinically similar genetic disorders, including Noonan syndrome (NS),
      Costello syndrome (CS) and cardio-facio-cutaneous syndrome (CFC). Each of these
      syndromes has a wide spectrum of molecular etiology. The aim of the present study
      was to conduct a comprehensive genetic analysis of RAS/RAF/MEK/ERK pathway in
      these syndromes. METHODS: Three patients with NS and two patients with CS/CFC
      were examined. Peripheral blood samples were collected from all patients as well
      as from 100 healthy Japanese volunteers. The protein phosphatase, non-receptor
      type II (PTPN11), KRAS, HRAS, NRAS, BRAF, RAF1, Son of Sevenless (SOS1) and
      MEK1genes were analyzed. RESULTS: In a patient with a severe Noonan phenotype, a
      rare PTPN11 mutation was detected: A to G transition at position 172, causing an
      N58D substitution within the N-SH2 domain. In a CS/CFC patient no HRAS mutations
      were found, but a novel SOS1 missense mutation was found: A to G transition at
      position 473, causing a T158A substitution within domain of histone-like fold
      (HF). CONCLUSIONS: A case mimicking CS with SOS1 T158A substitution, which has
      not been reported previously in CS, revealed the complex relationship between the
      genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.

PMID- 20030749
TI  - Increased mucosal expression of GATA-3 and STAT-4 in pediatric ulcerative
      colitis.
AB  - BACKGROUND: Serum pro-inflammatory cytokine levels are frequently elevated in the
      acute phase of pediatric inflammatory bowel disease (IBD). Because the role of
      pro-inflammatory cytokine in the acute phase of pediatric IBD has not been well
      investigated, the serum levels of pro-inflammatory cytokines and the expression
      of Th1 and Th2 signaling molecules in mucosa from the acute phase of pediatric
      IBD were examined. METHODS: Twenty children with ulcerative colitis (UC; mean
      age, 9.95 +/- 4.10 years) and 12 with Crohn's disease (CD; mean age, 10.0 +/-
      4.90 years) were enrolled for the serum cytokine (interleukin [IL]-4, IL-5, IL-6,
      tumor necrosis factor-alpha, tumor growth factor-beta1, and interferon-gamma)
      assay. Expression of T-helper cell 1 (Th1) (T-box expressed in T cells: T-bet and
      signal transducer and activator of transcription-4: STAT-4) and Th2 (GATA-3 and
      STAT-6) signaling molecules was examined on real-time polymerase chain reaction
      using mucosal samples from eight children in the acute phase of UC, eight with CD
      and eight controls. RESULTS: Significant elevation of serum IL-4 and IL-6 levels
      was detected at the acute phase of pediatric UC and CD compared with levels at
      remission (P < 0.05 in each). The mucosal expression of GATA-3 and STAT-4 was
      significantly enhanced in the acute phase of pediatric UC compared with normal
      mucosa. No significant difference was observed in the expression of all examined
      molecules in the acute phase of pediatric CD. CONCLUSIONS: IL-4 and its signaling
      molecule GATA-3, as well as the Th1 signaling molecule STAT-4, are involved in
      the pathogenesis of acute phase of pediatric UC.

PMID- 20030750
TI  - G-fibres in storage roots of Trifolium pratense (Fabaceae): tensile stress
      generators for contraction.
AB  - Root contraction has been described for many species within the plant kingdom for
      over a century, and many suggestions have been made for mechanisms behind these
      contractions. To move the foliage buds deeper into the soil, the proximal part of
      the storage root of Trifolium pratense contracts by up to 30%. Anatomical studies
      have shown undeformed fibres next to strongly deformed tissues. Raman imaging
      revealed that these fibres are chemically and structurally very similar to poplar
      (Populus) tension wood fibres, which are known to generate high tensile stresses
      and bend leaning stems or branches upright. Analogously, an almost pure
      cellulosic layer is laid down in the lumen of certain root fibres, on a thin
      lignified secondary cell wall layer. To reveal its stress generation capacities,
      the thick cellulosic layer, reminiscent of a gelatinous layer (G-layer) in
      tension wood, was selectively removed by enzymatic treatment. A substantial
      change in the dimensions of the isolated wood fibre bundles was observed. This
      high stress relaxation indicates the presence of high tensile stress for root
      contraction. These findings indicate a mechanism of root contraction in T.
      pratense (red clover) actuated via tension wood fibres, which follows the same
      principle known for poplar tension wood.

PMID- 20030751
TI  - Ethylene perception is involved in female cucumber flower development.
AB  - It is well established that ethylene promotes female flower development in
      cucumber. However, little is known about how the gaseous hormone selectively
      affects female flowers, and what mechanism it uses. Previously, we found organ
      specific DNA damage in the primordial anther of female cucumber flowers. This
      finding led to a hypothesis that ethylene might promote female flower development
      via the organ-specific induction of DNA damage in primordial anthers. In this
      study, we tested this hypothesis first by demonstrating ethylene induction of DNA
      damage via the ethylene signaling pathway using cucumber protoplasts. Then, using
      representative component genes of the ethylene signaling pathway as probes, we
      found that one of the ethylene receptors, CsETR1, was temporally and spatially
      downregulated in the stamens of stage-6 female cucumber flowers, especially along
      with the increase of the nodes. Furthermore, by constructing transgenic
      Arabidopsis plants with organ-specific expression of antisense CsETR1 under the
      control of an AP3 promoter to downregulate ETR1 expression in the stamens, we
      generated Arabidopsis 'female flowers', in which the abnormal stamens mimic those
      of female cucumber flowers. Our data suggest that ethylene perception is involved
      in the arrest of stamen development in female cucumber flowers through the
      induction of DNA damage. This opens up a novel perspective and approach to solve
      the half-century-long puzzle of how gaseous ethylene selectively promotes female
      flowers in the monoecious cucumber plant.

PMID- 20030752
TI  - An engineered C-terminal disulfide bond can partially replace the phaseolin
      vacuolar sorting signal.
AB  - Seed storage proteins accumulate either in the endoplasmic reticulum (ER) or in
      vacuoles, and it would appear that polymerization events play a fundamental role
      in regulating the choice between the two destinies of these proteins. We
      previously showed that a fusion between the Phaseolus vulgaris vacuolar storage
      protein phaseolin and the N-terminal half of the Zea mays prolamin gamma-zein
      forms interchain disulfide bonds that facilitate the formation of ER-located
      protein bodies. Wild-type phaseolin does not contain cysteine residues, and
      assembles into soluble trimers that transiently polymerize before sorting to the
      vacuole. These transient interactions are abolished when the C-terminal vacuolar
      sorting signal AFVY is deleted, indicating that they play a role in vacuolar
      sorting. We reasoned that if the phaseolin interactions directly involve the C
      terminus of the polypeptide, a cysteine residue introduced into this region could
      stabilize these transient interactions. Biochemical studies of two mutated
      phaseolin proteins in which a single cysteine residue was inserted at the C
      terminus, in the presence (PHSL*) or absence (Delta 418*) of the vacuolar signal
      AFVY, revealed that these mutated proteins form disulphide bonds. PHSL* had
      reduced protein solubility and a vacuolar trafficking delay with respect to wild
      type protein. Moreover, Delta 418* was in part redirected to the vacuole. Our
      experiments strongly support the idea that vacuolar delivery of phaseolin is
      promoted very early in the sorting process, when polypeptides are still contained
      within the ER, by homotypic interactions.

PMID- 20030753
TI  - Vacuolar sorting receptors (VSRs) and secretory carrier membrane proteins
      (SCAMPs) are essential for pollen tube growth.
AB  - Vacuolar sorting receptors (VSRs) are type-I integral membrane proteins that
      mediate biosynthetic protein traffic in the secretory pathway to the vacuole,
      whereas secretory carrier membrane proteins (SCAMPs) are type-IV membrane
      proteins localizing to the plasma membrane and early endosome (EE) or trans-Golgi
      network (TGN) in the plant endocytic pathway. As pollen tube growth is an
      extremely polarized and highly dynamic process, with intense anterograde and
      retrograde membrane trafficking, we have studied the dynamics and functional
      roles of VSR and SCAMP in pollen tube growth using lily (Lilium longiflorum)
      pollen as a model. Using newly cloned lily VSR and SCAMP cDNA (termed LIVSR and
      LISCAMP, respectively), as well as specific antibodies against VSR and SCAMP1 as
      tools, we have demonstrated that in growing lily pollen tubes: (i) transiently
      expressed GFP-VSR/GFP-LIVSR is located throughout the pollen tubes, excepting the
      apical clear-zone region, whereas GFP-LISCAMP is mainly concentrated in the tip
      region; (ii) VSRs are localized to the multivesicular body (MVB) and vacuole,
      whereas SCAMPs are localized to apical endocytic vesicles, TGN and vacuole; and
      (iii) microinjection of VSR or SCAMP antibodies and LlVSR small interfering RNAs
      (siRNAs) significantly reduced the growth rate of the lily pollen tubes. Taken
      together, both VSR and SCAMP are required for pollen tube growth, probably
      working together in regulating protein trafficking in the secretory and endocytic
      pathways, which need to be coordinated in order to support pollen tube
      elongation.

PMID- 20030754
TI  - Wavelet denoising of vaginal pulse amplitude.
AB  - Vaginal pulse amplitude (VPA) has been the most commonly analyzed signal of the
      vaginal photoplethysmograph. Frequent, large, and variable-morphology artifacts
      typically have crowded this signal. These artifacts usually were corrected by
      hand, which may have introduced large differences in outcomes across
      laboratories. VPA signals were collected from 22 women who viewed a neutral film
      and a sexual film. An automated, wavelet-based, denoising algorithm was compared
      against the uncorrected signal and the signal corrected in the typical manner (by
      hand). The automated wavelet denoising resulted in the same pattern of results as
      the hand-corrected signal. The wavelet procedure automated artifact reduction in
      the VPA, and this mathematical instantiation permits the comparison of competing
      methods to improve signal:noise in the future.

PMID- 20030755
TI  - Retest reliability of medial frontal negativities during performance monitoring.
AB  - The error-related negativity (ERN) and feedback-related negativity (FRN) have
      been used as electrophysiological indices of performance monitoring produced in
      response to internally generated (errors) and externally generated (feedback)
      activations of the anterior cingulate cortex (ACC). No studies to date have
      systematically examined the measurement reliability of these components. In this
      article, we present the retest reliability of the ERN and FRN during response
      tasks designed to elicit errors or feedback responses on two occasions. Data from
      four experiments are presented in which participants performed tasks over various
      periods of time. Results indicate good retest reliability of the ERN and FRN
      amplitudes and source generation of these components. The present article
      provides important validation of the ERN and FRN as stable and trait-like
      electrophysiological reflections of performance monitoring and ACC functional
      integrity.

PMID- 20030756
TI  - Is freezing an adaptive reaction to threat? Evidence from heart rate reactivity
      to emotional pictures in victims of war and torture.
AB  - The influence of past traumatic experiences on the defense cascade in response to
      affective pictures was examined in survivors of war and torture. Trauma-exposed
      refugees with and without Posttraumatic Stress Disorder (PTSD) as well as healthy
      individuals viewed 75 pictures that varied in emotional content. Heart rate (HR)
      was recorded during the flickering stimulation of affective pictures in the
      context of a steady-state experiment. Whereas healthy controls showed the typical
      orienting response to aversive stimuli, PTSD patients reacted with an almost
      immediate increase in HR toward unpleasant pictures. Trauma-exposed participants
      without PTSD showed an indiscriminate orienting response regardless of picture
      category. The present findings argue for a faster flight/fight response to
      threatening cues in PTSD. In contrast, trauma-exposed controls seem to exhibit a
      state of permanent alertness toward a wide range of stimuli.

PMID- 20030757
TI  - Effects of essential hypertension on short latency human somatosensory-evoked
      potentials.
AB  - Reduced perception of somatosensory stimulation in patients with essential
      hypertension may be due to deficits in the ascending somatosensory pathway.
      Function in the ascending somatosensory pathway was assessed by measuring N9,
      N13, and N20 somatosensory-evoked potentials in 14 unmedicated essential
      hypertensives and 22 normotensives. N9 amplitudes were smaller and N13 amplitudes
      marginally smaller in hypertensives than normotensives. N9 amplitudes were
      inversely associated with blood pressure. N20 amplitudes and N9, N13, and N20
      latencies did not differ between groups. In addition, plexus-to-cord, cord-to
      cortex, and plexus-to-cortex conduction times were not different between groups.
      These data suggest that hypertension affects the peripheral nervous system by
      reducing the number of active sensory nerve fibers without affecting myelination.
      However, hypertension does not seem to affect the afferent somatosensory pathway
      within the brain.

PMID- 20030759
TI  - Unexpected action effects elicit deviance-related brain potentials and cause
      behavioral delay.
AB  - To examine how people deal with perceivable consequences of their voluntary
      actions, we recorded event-related potentials (ERPs) during a self-paced, two
      choice random generation task. Sixteen participants were asked to press one of
      two buttons randomly at a regular but self-selected interval of once per 1-2 s.
      Each button press produced either a 1000-Hz or 2000-Hz tone, but participants
      were told that the tones were irrelevant to the task. The button-tone
      combinations were initially fixed, but in subsequent blocks, a button press
      infrequently produced the tone associated with the opposite button (p=.15). This
      cognitively mismatched tone elicited N2, P3, and late positive potential (or
      positive slow wave) of the ERP and delayed the timing of the next button press.
      These results suggest that action effects are difficult to ignore and that an
      action effect that is different from a performer's expectation may cause task
      disruption.

PMID- 20030758
TI  - Don't look at me in anger! Enhanced processing of angry faces in anticipation of
      public speaking.
AB  - Anxiety is supposed to enhance the processing of threatening information. Here,
      we investigated the cortical processing of angry faces during anticipated public
      speaking. To elicit anxiety, a group of participants was told that they would
      have to perform a public speech. As a control condition, another group was told
      that they would have to write a short essay. During anticipation of these tasks,
      participants saw facial expressions (angry, happy, and neutral) while
      electroencephalogram was recorded. Event-related potential analysis revealed
      larger N170 amplitudes for angry compared to happy and neutral faces in the
      anxiety group. The early posterior negativity as an index of motivated attention
      was also enhanced for angry compared to happy and neutral faces in participants
      anticipating public speaking. These results indicate that fear of public speaking
      influences early perceptual processing of faces such that especially the
      processing of angry faces is facilitated.

PMID- 20030760
TI  - Cardiovascular patterns associated with appetitive and defensive activation
      during affective picture viewing.
AB  - In this study we assessed blood pressure (BP), heart rate (HR), stroke volume
      (SV), cardiac output (CO), and total peripheral resistance (TPR) in response to
      13 picture series in 37 participants in order to investigate their hemodynamic
      response associated with activation of the appetitive and defensive motivational
      systems underlying emotional experience. BP and SV, but not TPR, increased with
      increasing self-rated arousal, whereas HR decelerated more in response to
      negative than positive and neutral pictures. These findings suggest that
      modulation of the cardiovascular response to pictures is primarily myocardial.
      The observed response pattern is consistent with a configuration of cardiac
      sympathetic-parasympathetic coactivation. The relationships between self-rated
      arousal, BP, and SV were mainly exhibited by men, suggesting that increases in
      the sympathetic inotropic effect to the heart with self-rated arousal may be
      larger in men than in women.

PMID- 20030761
TI  - ERP correlates of linear hand movements in a motor reproduction task.
AB  - Blindfolded participants performed one-dimensional movements towards a mechanical
      stop and back to the start. After a varying delay, they had to reproduce the
      encoded target position by a second mechanically unrestricted movement. Average
      event-related potentials accompanying the "encoding" and the "reproduction"
      movements revealed a biphasic waveshape over primary sensorimotor areas. The
      first negative deflection was the gradually increasing motor potential (MP) that
      precedes movement onset. This was followed by a second negative component (N4)
      starting about 100 ms after movement onset. Its amplitude and latency increased
      with increasing movement distance and reached its maximum in unrestricted
      movements (i.e., during reproduction) shortly before the deceleration peak. These
      results show that rapid hand movements are accompanied by non-continuous and
      highly distance specific activity changes measured over the sensorimotor cortex.

PMID- 20030762
TI  - Using multilevel path analysis in analyzing 24-h ambulatory physiological
      recordings applied to medically unexplained symptoms.
AB  - A non-clinical group high on heterogeneous medically unexplained symptoms (MUS;
      n=97) was compared with healthy controls (n=66) on the within-subject
      relationships between physiological measures using multilevel path analysis.
      Momentary experienced somatic complaints, mood (tension and depression), cardiac
      autonomic activity (inter-beat intervals, pre-ejection period (PEP), and
      respiratory sinus arrhythmia (RSA)) and respiration (rate and partial pressure of
      CO(2) at the end of a normal expiration) were monitored for 24 h using electronic
      diary and ambulatory devices. Relationships between measures were controlled for
      diurnal variation and individual means. Only subtle group differences were found
      in the diurnal rhythm and in the within-subject relationships between
      physiological measures. For participants high on MUS, within-subject changes in
      bodily symptoms were related to changes in mood, but only marginally to the
      physiological measures. Results of the current path analysis confirm the
      subordinate role of cardiac autonomic and respiratory parameters in MUS.

PMID- 20030763
TI  - Sport is not always healthy: Executive brain dysfunction in professional boxers.
AB  - We measured ERPs of professional boxers in a Go/No-Go task, comparing them to
      fencers and non-athletes. Results showed that fencing improved attention and
      motor response control, but boxing did not. More strikingly, in boxers, as in
      brain trauma patients, the P3 component was delayed and reduced. The P3 delay of
      boxers was correlated with the amount of performed sport exercise. Furthermore,
      in terms of behavior, boxers showed increased intra-individual variability and
      switch cost. Results were consistent with the hypothesis of specific impairment
      at the level of response inhibition processing. We suggest that this impairment
      is derived from the cumulative effect of blows to the head. The changes found in
      boxers suggest that ERPs and reaction times may be a tool for early detection of
      specific brain dysfunction.

PMID- 20030764
TI  - Empathy and error processing.
AB  - Recent research suggests a relationship between empathy and error processing.
      Error processing is an evaluative control function that can be measured using
      post-error response time slowing and the error-related negativity (ERN) and post
      error positivity (Pe) components of the event-related potential (ERP). Thirty
      healthy participants completed two measures of empathy, the Interpersonal
      Reactivity Index (IRI) and the Empathy Quotient (EQ), and a modified Stroop task.
      Post-error slowing was associated with increased empathic personal distress on
      the IRI. ERN amplitude was related to overall empathy score on the EQ and the
      fantasy subscale of the IRI. The Pe and measures of empathy were not related.
      Results remained consistent when negative affect was controlled via partial
      correlation, with an additional relationship between ERN amplitude and empathic
      concern on the IRI. Findings support a connection between empathy and error
      processing mechanisms.

PMID- 20030765
TI  - Cardiovascular measures independently predict performance in a university course.
AB  - The factors that predict academic performance are of substantial importance yet
      are not understood fully. This study examined the relationship between
      cardiovascular markers of challenge/threat motivation and university course
      performance. Before the first course exam, participants gave speeches on
      academics-relevant topics while their cardiovascular responses were recorded.
      Participants who exhibited cardiovascular markers of relative challenge (lower
      total peripheral resistance and higher cardiac output) while discussing academic
      interests performed better in the subsequent course than those who exhibited
      cardiovascular markers of relative threat. This relationship remained significant
      after controlling for two other important predictors of performance (college
      entrance exam score and academic self-efficacy). These results have implications
      for the challenge/threat model and for understanding academic goal pursuit.

PMID- 20030766
TI  - Reducing overconfidence in the interval judgments of experts.
AB  - Elicitation of expert opinion is important for risk analysis when only limited
      data are available. Expert opinion is often elicited in the form of subjective
      confidence intervals; however, these are prone to substantial overconfidence. We
      investigated the influence of elicitation question format, in particular the
      number of steps in the elicitation procedure. In a 3-point elicitation procedure,
      an expert is asked for a lower limit, upper limit, and best guess, the two limits
      creating an interval of some assigned confidence level (e.g., 80%). In our 4-step
      interval elicitation procedure, experts were also asked for a realistic lower
      limit, upper limit, and best guess, but no confidence level was assigned; the
      fourth step was to rate their anticipated confidence in the interval produced. In
      our three studies, experts made interval predictions of rates of infectious
      diseases (Study 1, n = 21 and Study 2, n = 24: epidemiologists and public health
      experts), or marine invertebrate populations (Study 3, n = 34: ecologists and
      biologists). We combined the results from our studies using meta-analysis, which
      found average overconfidence of 11.9%, 95% CI [3.5, 20.3] (a hit rate of 68.1%
      for 80% intervals)-a substantial decrease in overconfidence compared with
      previous studies. Studies 2 and 3 suggest that the 4-step procedure is more
      likely to reduce overconfidence than the 3-point procedure (Cohen's d = 0.61,
      [0.04, 1.18]).

PMID- 20030767
TI  - Conundrums with uncertainty factors.
AB  - The practice of uncertainty factors as applied to noncancer endpoints in the IRIS
      database harkens back to traditional safety factors. In the era before risk
      quantification, these were used to build in a "margin of safety." As risk
      quantification takes hold, the safety factor methods yield to quantitative risk
      calculations to guarantee safety. Many authors believe that uncertainty factors
      can be given a probabilistic interpretation as ratios of response rates, and that
      the reference values computed according to the IRIS methodology can thus be
      converted to random variables whose distributions can be computed with Monte
      Carlo methods, based on the distributions of the uncertainty factors. Recent
      proposals from the National Research Council echo this view. Based on
      probabilistic arguments, several authors claim that the current practice of
      uncertainty factors is overprotective. When interpreted probabilistically,
      uncertainty factors entail very strong assumptions on the underlying response
      rates. For example, the factor for extrapolating from animal to human is the same
      whether the dosage is chronic or subchronic. Together with independence
      assumptions, these assumptions entail that the covariance matrix of the logged
      response rates is singular. In other words, the accumulated assumptions entail a
      log-linear dependence between the response rates. This in turn means that any
      uncertainty analysis based on these assumptions is ill-conditioned; it
      effectively computes uncertainty conditional on a set of zero probability. The
      practice of uncertainty factors is due for a thorough review. Two directions are
      briefly sketched, one based on standard regression models, and one based on
      nonparametric continuous Bayesian belief nets.

PMID- 20030768
TI  - Probability of exporting infected carcasses from vaccinated pigs following a foot
      and-mouth disease epidemic.
AB  - Emergency vaccination is an effective control strategy for foot-and-mouth disease
      (FMD) epidemics in densely populated livestock areas, but results in a six-month
      waiting period before exports can be resumed, incurring severe economic
      consequences for pig exporting countries. In the European Union, a one-month
      waiting period has been discussed based on negative test results in a final
      screening. The objective of this study was to analyze the risk of exporting FMD
      infected pig carcasses from a vaccinated area: (1) directly after final screening
      and (2) after a six-month waiting period. A risk model has been developed to
      estimate the probability that a processed carcass was derived from an FMD
      infected pig (P(carc)). Key variables were herd prevalence (P(H)), within-herd
      prevalence (P(A)), and the probability of detection at slaughter (P(SL)). P(H)
      and P(A) were estimated using Bayesian inference under the assumption that,
      despite all negative test results, > or =1 infected pigs were present. Model
      calculations indicated that P(carc) was on average 2.0 x 10(-5) directly after
      final screening, and 1.7 x 10(-5) after a six-month waiting period. Therefore,
      the additional waiting time did not substantially reduce P(carc). The estimated
      values were worst-case scenarios because only viraemic pigs pose a risk for
      disease transmission, while seropositive pigs do not. The risk of exporting FMD
      via pig carcasses from a vaccinated area can further be reduced by heat treatment
      of pork and/or by excluding high-risk pork products from export.

PMID- 20030769
TI  - 'We got the whole story all at once': physiotherapists' use of key questions when
      meeting patients with long-standing pain.
AB  - Long-standing musculoskeletal pain has many dimensions. Physiotherapy lacks a
      tested method of dialogue with which physiotherapists and patients can together
      explore pain in all its complexity. The present aim was to find out how
      physiotherapists experienced the influence of systematically prepared key
      questioning on their relation to, and understanding of, patients with long
      standing pain. A group of six physiotherapists with long experience of pain
      rehabilitation used such questions in their encounters with their patients. Two
      periods of work with the questions were followed by discussions in which the
      physiotherapists shared their experience in a joint focus group. Verbatim
      transcripts of the discussions constitute the data of the study. A
      phenomenographic method was used for the analysis. The responses to the key
      questions gave the physiotherapists an insight into the patient as a person. The
      questions started a process of change in the patient, and changed the
      physiotherapist's relation to her or him. The patient expressed feelings and
      experience, and this also seemed to encourage a change in chosen coping
      strategies. This new content of the interaction challenged the physiotherapist's
      role, thus raising questions about her professional mandate.

PMID- 20030770
TI  - Swedish District Nurses' experiences on the use of information and communication
      technology for supporting people with serious chronic illness living at home--a
      case study.
AB  - The aim of this case study was to describe two District Nurses' (DN) experiences
      of using information and communication technology (ICT) to communicate with
      chronically ill people in their homes. An electronic messaging program via
      computers and mobile phones with an Internet connection was used, enabling DNs
      and the ill people to exchange messages to and from anywhere. The program
      comprised different virtual rooms, and communication was via text messages. The
      DNs in this study used the program two to four times each week from November 2003
      to March 2004. Semi-structured interviews were performed before, during and after
      the implementation of the new technology and were analysed using thematic content
      analysis. The results showed that the DNs felt that the technology increased
      accessibility to nursing care through a more direct communication with the ill
      person meaning that a more trusting relationship could be created. The DNs also
      experienced that the use of ICT saved working time. This study indicates that the
      use of ICT for communication allowed the DN to better support a chronically ill
      person at home leading to improved home nursing care. This method of
      communication cannot replace physical presence, but can be seen as a complement
      to nursing care at home.

PMID- 20030771
TI  - Watching television in later life: a deeper understanding of TV viewing in the
      homes of old people and in geriatric care contexts.
AB  - A secret among staff at nursing homes is that they are often ambivalent about old
      residents spending more time in watching TV as it is a common cultural perception
      that it makes the viewer passive. The purpose of this paper is to highlight the
      importance of reflecting on the TV viewing habits that old people bring with them
      when they move into geriatric care. The findings are based on a study involving
      qualitative interviews and observations in two nursing home settings - urban and
      rural - of 20 persons between 82 and 100 years of age. The results confirm that
      TV viewing is far from a passive activity. Instead, it contributes to structuring
      daily life, to satisfying old peoples' needs for reflection and contemplation and
      to remain socially integrated. As such, TV viewing makes a significant
      contribution to their capacity to cope with disengagement in old age and can be
      used as a way of promoting communication and well-being in geriatric care.

PMID- 20030772
TI  - How to cope with the mask? Experiences of mask treatment in patients with acute
      chronic obstructive pulmonary disease-exacerbations.
AB  - The aim of the study was to focus on important aspects and issues associated with
      bi-level positive airway pressure (BPAP) mask treatment in acute exacerbation of
      chronic obstructive pulmonary disease based on the experiences of patients and
      nurses. The study has a qualitative design with a phenomenological approach. The
      data are based on qualitative in-depth interviews with five patients who had used
      BPAP-mask treatment intermittently over several days in the acute stages and a
      focus group with eight experienced nurses from a specialized unit in a Norwegian
      university hospital. The data have been analysed on the basis of Amadeo Giorgi's
      phenomenological method. Findings are discussed in the light of the Norwegian
      philosopher Kari Martinsen's nursing philosophy with practical implications. The
      essential structure of being treated with BPAP-mask from the patients' point of
      view may be characterised as a feeling of being trapped in a situation of
      complete dependence on others, combined with a will to mobilize inner strength.
      The essential structure is presented through three themes describing the
      patient's lived experience: Anxiety, panic and loss of control, regaining control
      and trust through skilled help, and a mobilization of willpower. The nurses'
      experiences point to the challenges related to individual needs, ethics,
      technical, medical and relational competence in addition to constraints on time.
      The study concludes that mask treatment can be a traumatic experience for the
      patients. The interplay between dependence and autonomy in the patient's
      interaction with health care providers, such as deciding when to take breaks,
      getting enough sleep, mobilizing inner strength and establishing trust and
      security are important factors in coping with the mask. Clinical competence, the
      ability to articulate impressions, and sufficient time on the part of health
      workers are other aspects that can be decisive to how well the patient tolerates
      BPAP-mask treatment.

PMID- 20030773
TI  - The meaning of a consultation with the diabetes nurse specialist.
AB  - OBJECTIVE: The aim of this study was to elucidate the essential meaning of a
      consultation between diabetes nurse specialists and patients to gain a deeper
      understanding of the patients' experiences. METHODS: Twenty patients with type 2
      diabetes were interviewed about their experience of a consultation at an annual
      check-up with the diabetes nurse specialist. A phenomenological hermeneutic
      method was used in the analysis and interpretation of the text. RESULTS: The
      patient's experience of a consultation was interpreted as manifestation of hold
      on the disease control. This means a safeguard to continue daily life shown in
      the four themes being controlled, feeling exposed, feeling comfortable, and
      feeling prepared. CONCLUSION: The patients' experiences of a consultation with
      the diabetes nurse specialist became the basis for a health maintenance process
      in dealing with critical health-disease aspects. IMPLICATIONS TO PRACTICE: In a
      consultation, professionals have to take into account the potential emotional
      turbulence that disease progression can mean to a patient. Diabetes care implies
      patient dependence on support to avoid a potential self-management insufficiency
      and call attention to professionals' time for listening to patients' perceptions.

PMID- 20030774
TI  - Utilization of medical healthcare among people receiving long-term care at home
      or in special accommodation.
AB  - AIM: To investigate the utilization of medical healthcare, hospital care and
      outpatient care, during a 1-year period in relation to informal care,
      multimorbidity, functional status and health complaints and to long-term care at
      home or in special accommodation among people aged 65+, with one or more hospital
      admissions and receiving long-term care. METHOD: A total of 694 people receiving
      long-term care during the year 2001 were studied. Data were collected by means of
      the administrative registers Patient Administrative Support in Skane and
      PrivaStat and through the study Good Ageing in Skane. Those at home and those in
      special accommodation were compared regarding utilization of medical healthcare,
      informal care, multimorbidity, functional status and health complaints. Multiple
      logistic regression analysis was performed using at home vs. in special
      accommodation as the dependent variable and also two multiple linear regression
      analyses using the number of hospital stays and the number of contacts with the
      physician in outpatient care separately as dependent variables. FINDINGS: Those
      at home were significantly younger (mean age: 81 vs. 84 years) and less dependent
      in personal and instrumental activities of daily living (PADL/IADL) than those in
      special accommodation. A larger proportion of those at home was admitted to
      hospital three times or more (21 vs. 14%) and they had significantly more
      contacts with physicians in outpatient care (md: 10 vs. md: 7). Informal care was
      associated with care at home (OR = 0.074) and with utilization of outpatient care
      (B = 2.045). Dependency in PADL was associated with care in special accommodation
      (OR = 1.375) and with utilization of hospital care (B = -0.060) and outpatient
      care (B = -0.581). CONCLUSION: Medical healthcare seems more accessible to those
      who live at home are younger, less dependent and who have access to informal
      caregivers.

PMID- 20030775
TI  - Effects of combined endurance and strength training on muscle strength, power and
      hypertrophy in 40-67-year-old men.
AB  - Both strength and endurance training have several positive effects on aging
      muscle and physical performance of middle-aged and older adults, but their
      combination may compromise optimal adaptation. This study examined the possible
      interference of combined strength and endurance training on neuromuscular
      performance and skeletal muscle hypertrophy in previously untrained 40-67-year
      old men. Maximal strength and muscle activation in the upper and lower
      extremities, maximal concentric power, aerobic capacity and muscle fiber size and
      distribution in the vastus lateralis muscle were measured before and after a 21
      week training period. Ninety-six men [mean age 56 (SD 7) years] completed high
      intensity strength training (S) twice a week, endurance training (E) twice a
      week, combined training (SE) four times per week or served as controls (C). SE
      and S led to similar gains in one repetition maximum strength of the lower
      extremities [22 (9)% and 21 (8)%, P<0.001], whereas E and C showed minor changes.
      Cross-sectional area of type II muscle fibers only increased in S [26 (22)%,
      P=0.002], while SE showed an inconsistent, non-significant change [8 (35)%,
      P=0.73]. Combined training may interfere with muscle hypertrophy in aging men,
      despite similar gains in maximal strength between the strength and the combined
      training groups.

PMID- 20030776
TI  - To stretch or not to stretch: the role of stretching in injury prevention and
      performance.
AB  - Stretching is commonly practiced before sports participation; however, effects on
      subsequent performance and injury prevention are not well understood. There is an
      abundance of literature demonstrating that a single bout of stretching acutely
      impairs muscle strength, with a lesser effect on power. The extent to which these
      effects are apparent when stretching is combined with other aspects of a pre
      participation warm-up, such as practice drills and low intensity dynamic
      exercises, is not known. With respect to the effect of pre-participation
      stretching on injury prevention a limited number of studies of varying quality
      have shown mixed results. A general consensus is that stretching in addition to
      warm-up does not affect the incidence of overuse injuries. There is evidence that
      pre-participation stretching reduces the incidence of muscle strains but there is
      clearly a need for further work. Future prospective randomized studies should use
      stretching interventions that are effective at decreasing passive resistance to
      stretch and assess effects on subsequent injury incidence in sports with a high
      prevalence of muscle strains.

PMID- 20030777
TI  - An examination of serotonin and psychological variables in the relationship
      between exercise and mental health.
AB  - Research has revealed that exercise is effective for reducing symptoms of
      depression and anxiety. The mechanisms by which these reductions occur, however,
      have not been widely studied. To examine several potential theories, a
      prospective, randomized, 7-week exercise intervention was conducted. Untrained
      participants were randomly assigned to an aerobic exercise group or to a
      stretching-control group. Participants completed several questionnaires to assess
      psychological variables, including measures of depression and anxiety, and blood
      was drawn at pre- and post-test to measure serum serotonin levels. A mixed-design
      ANOVA revealed that the exercise group had lower levels of depression than the
      stretching-control group after the intervention. The exercise group also showed a
      larger percentage decrease in serotonin than the stretching-control group. This
      reduction in blood serotonin after exercise is similar to the effects of
      selective serotonin reuptake inhibitors. Additionally, percent change in
      serotonin was found to partially mediate the relationship between exercise and
      depression.

PMID- 20030778
TI  - Recording injuries among World Cup skiers and snowboarders: a methodological
      study.
AB  - No long-term injury surveillance programs exist for competitive skiing or
      snowboarding. The objective of this study was, therefore, to compare different
      methods to record injuries among World Cup athletes in alpine, freestyle, and
      cross-country skiing, snowboarding, ski jumping and Nordic combined. Information
      regarding injuries sustained during the 2006-2007 winter season was recorded
      through three separate and independent systems: prospective injury reports by
      technical delegates (TD) from the International Ski Federation, prospective
      medical team registration by selected teams, and retrospective athlete interviews
      at the end of the season. A total of 100 unique injuries to 602 World Cup
      athletes were identified from any of the three recording methods. Of these, 91%
      were registered through the athlete interviews, 47% by the medical team
      registration and 27% by the TD reports. Only 20 injuries (20%) were captured by
      all three methods. A total of 64 time-loss injuries were registered. The
      interviews captured 60 (94%), the medical team registration 39 (61%), and the TD
      reports 23 (36%) time-loss injuries, while 18 (28%) were registered by all three
      systems. Retrospective interviews with athletes/coaches regarding injuries during
      the last 6 months gave the most complete picture of injuries to World Cup skiers
      and snowboarders.

PMID- 20030779
TI  - Stress-related hormonal and psychological changes to official youth Taekwondo
      competitions.
AB  - The aim of this study was to evaluate the effects of an official Taekwondo
      competition on the heart rate (HR), salivary alpha-amylase (sA-A), salivary free
      cortisol (sC), and Profile of Mood States (POMS) in 10 young male (14+/-0 years)
      and six female (13+/-1 years) athletes. POMS and hormones were measured 15 min
      before and directly after the competition. During the recovery phase (30 and 90
      min), sA-A and sC were also measured. HR measured during the competition was
      expressed as a percentage of individual's maximal heart rate (%HR(max) ) to
      evaluate the intensity of exercise. During the competition, athletes spent 65% of
      the time working at HR>90% of individuals HR(max). A significant increase
      (P<0.0001) in sA-A (115%) was observed at the end of the match. At 30 min of
      recovery, sA-A returned to the pre-competition level. The peak sC values were
      observed at 30 min of recovery (P<0.001), returning to the pre-competition level
      at 90 min of recovery. A gender difference (P=0.01) emerged only for sC, although
      a similar trend was observed for female and male athletes. Significantly higher
      post-match scores emerged for Anger-hostility (pre: 6.1+/-1.1, post: 11.2+/-1.9;
      P=0.03) and Depression-dejection (pre: 4.5+/-0.5, post: 10.2+/-1.9; P=0.006),
      whereas the reverse picture was observed for Vigour-activity (pre: 23.2+/-1.2,
      post: 16.3+/-1.7; P=0.0006). Taekwondo competition results in temporary changes
      in the stress-related parameters measured in this study. The present findings
      suggest that this experimental paradigm can represent a useful model for further
      research on the effects of various stressors (i.e., training and competition) in
      Taekwondo athletes of different levels (i.e., novice, international).

PMID- 20030780
TI  - Skyscraper running: physiological and biomechanical profile of a novel sport
      activity.
AB  - Skyscraper running is here analyzed in terms of mechanical and metabolic
      requirements, both at the general and at the individual level. Skyscraper
      runners' metabolic profile has been inferred from the total mechanical power
      estimated in 36 world records (48-421 m tall buildings), ranked by gender and age
      range. Individual athlete's performance (n=13) has been experimentally
      investigated during the Pirelli Vertical Sprint, with data loggers for altitude
      and heart rate (HR). At a general level, a non-linear regression of Wilkie's
      model relating maximal mechanical power to event duration revealed the gender and
      age differences in terms of maximum aerobic power and anaerobic energy resources
      particularly needed at the beginning of the race. The total mechanical power was
      found to be partitioned among: the fraction devolved to raise the body center of
      mass , the need to accelerate the limbs with respect to the body , and running in
      turns between flights of stairs . At the individual level, experiments revealed
      that these athletes show a metabolic profile similar to middle-distance runners.
      Furthermore, best skyscraper runners maintain a constant vertical speed and HR
      throughout the race, while others suddenly decelerate, negatively affecting the
      race performance.

PMID- 20030781
TI  - Differences in scapular and humeral head position between swimmers and non
      swimmers.
AB  - The aims of this study were to determine differences between swimmers/non
      swimmers, males/females and dominant/non-dominant sides for scapular and humeral
      head position, while accounting for size, and to determine the relationship
      between scapular and humeral head position. 46 teenage swimmers (30 females) and
      43 non-swimmers (28 females) were measured. The distances between (a) medial
      spine of the scapula and T3/4 (Superior Kibler), (b) inferior scapula and T7/8
      (Inferior Kibler) and (c) anterior acromion and anterior humeral head were
      recorded while teenagers stood with their hands-on hips. There was no main effect
      difference between swimmers and non-swimmers for scapular or humeral head
      position. There were interactions for swim status/dominance (Superior Kibler;
      P=0.005, Inferior Kibler; P<0.001) and swim status/gender (Superior Kibler;
      P=0.027). The humeral head was significantly further from the acromion on the
      dominant side (adjusted mean difference=1.4 mm, P=0.004). Little relationship
      between scapular and humeral head position was evident. Clinicians should be
      aware that swim status, in combination with gender or dominance may affect
      scapular position but does not affect humeral head position. Where swimming had
      an effect, it minimized differences between genders and sides. The small
      dominance effect on the humeral head position is unlikely to be clinically
      detectable.

PMID- 20030782
TI  - Functional movement test scores improve following a standardized off-season
      intervention program in professional football players.
AB  - The purpose of this study was to determine if an off-season intervention program
      was effective in improving Functional Movement Screen(TM) (FMS) scores in
      professional American football players. Pre- and post-intervention FMS scores
      were obtained on 62 subjects who completed a 7-week off-season intervention
      program. A repeated measures ANOVA was conducted to determine the effectiveness
      of the training program on FMS scores. A chi-square was performed to determine if
      there were a greater number of players who met the injury threshold and if
      asymmetries were reduced following intervention. Logistic regression was used to
      predict what factors were associated with failure (post-test score of <14). There
      was a positive main effect for time (P<0.01) and a greater number of individuals
      with a score >14 following the intervention. At post-test, 41 players were free
      of asymmetry as compared with 31 at the pre-test. The strongest predictor of
      program failure was a low squat score at pre-test. This study demonstrated that
      fundamental movement characteristics do change with a standardized intervention.
      Further research is required to determine if injury risk is reduced when a
      player's score improves beyond the established cut-off of 14 and/or asymmetry is
      resolved.

PMID- 20030783
TI  - Associations of physical activity with muscular fitness in adolescents.
AB  - The aim of this study was to examine the associations between objectively
      assessed physical activity (PA) and muscular fitness (MF) in adolescents, and to
      determine whether only resistance training exercise is associated with the
      increase of MF. A sample of 211 Spanish adolescents (105 girls) wore the
      ActiGraph monitor for 7 days. Participants also completed a fitness evaluation
      including three MF tests (handgrip strength, a 60-s abdominal test and a standing
      broad jump), a cardiorespiratory fitness assessment and anthropometric measures.
      A standardized MF score was computed using the three muscular tests. Adolescent
      participation in resistance training was self-reported. Linear regression showed
      that only vigorous PA was significantly (P=0.041) and positively (beta=0.133)
      associated with MF after adjustment by gender, age, pubertal status, BMI, and
      cardiorespiratory fitness. Significant differences in MF were found between youth
      in the lowest and upper tertiles of vigorous PA. Moreover, adolescents who were
      involved in resistance training had significantly higher MF scores compared with
      youth in low and medium tertiles of vigorous PA, but no significant differences
      were found when compared with non-lifters from the highest tertile of vigorous PA
      (P=0.356). These findings suggest that vigorous activity may be associated with
      indicators of MF in adolescents.

PMID- 20030784
TI  - Spinal modulations accompany peripheral fatigue during prolonged tennis playing.
AB  - To examine the time course of alteration in neural process (spinal loop
      properties) during prolonged tennis playing, 12 competitive players performed a
      series of neuromuscular tests every 30 min during a 3-h match protocol. Muscle
      activation (twitch interpolation) and normalized EMG activity were assessed
      during maximal voluntary contraction (MVC) of plantar flexors. Spinal reflexes
      and M-waves were evoked at rest (i.e., H(max) and M(max) , respectively) and
      during MVC (i.e., H(sup) , V-wave, M(sup) , respectively). MVC torque declined
      significantly (P<0.001) across the match protocol, due to decrease (P<0.001) in
      muscle activation and in normalized EMG activity. The impairment in MVC was
      significantly correlated (r=0.77; P<0.05) with the decline in muscle activation.
      H(max) /M(max) (P<0.001), H(sup) /M(sup) (P<0.01) and V/M(sup) (P<0.05) ratios
      were depressed with fatigue and decreased by ~80%, 46% and 61% at the end of
      exercise, respectively. Simultaneously, peak twitch torque and M-wave amplitude
      were significantly (P<0.01) altered with exercise, suggesting peripheral
      alterations. During prolonged tennis playing, the compromised voluntary strength
      capacity is linked to a reduced neural input to the working muscles. This central
      activation deficit partly results from a modulation in spinal loop properties.

PMID- 20030785
TI  - The Babel Tower revisited: SNPs - Indels - CNVs. Confusion in naming sequence
      variant always rises from ashes.

PMID- 20030786
TI  - HLA-G*0105N and HLA-G 14 bp dimorphisms in exon 8 in four distinct populations in
      mainland China.
AB  - In this study, we investigated human leukocyte antigen (HLA)-G*0105N and the 14
      bp deletion/insertion polymorphism in exon 8 of the HLA-G gene in 600 individuals
      from two southern Chinese Han populations (Hunan Han and Guangdong Han) and two
      northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol), we
      also studied the linkage disequilibrium (LD) between HLA-G and HLA-A locus in
      these four populations. Our data showed that (1) the allele and haplotype
      frequencies of HLA-G and HLA-A loci did not differ significantly between the two
      southern Chinese Han populations, and showed remarkable homogeneity in the two
      northern Chinese populations; (2) HLA-G*0105N had significantly higher
      frequencies in the two northern Chinese populations with a frequency of 10.1% in
      the Inner Mongolia Han population, HLA-G 14 bp deletion/insertion frequency did
      not differ significantly between the southern and northern Chinese populations;
      (3) Ewens-Watterson homozygosity statistics at HLA-G*0105N, HLA-G 14 bp
      deletion/insertion polymorphism and HLA-A were consistent with neutral
      expectations for all populations; (4) HLA-G*0105N allele harbored the HLA-G 14 bp
      insertion in exon 8 and was linked to HLA-A*30, five HLA-G*0105N homozygotes were
      detected in the four populations; (5) haplotypes HLA-A*30-HLA-G*0105N and HLA
      A*02-HLA-G 14 bp deletion were in significant LD across four populations, other
      LD patterns were more population-specific. Our data suggest that HLA-A*30-HLA
      G*0105N-HLA-G 14 bp insertion is a conserved haplotype, the ethnic and/or
      geographic difference in HLA-G*0105N and HLA-G 14 bp distribution could largely
      be attributable to demographic factors other than selection. The LD patterns
      uncovered will facilitate the understanding of HLA-G role in associations
      previously described between HLA-A subregion and diseases.

PMID- 20030787
TI  - Identification of a novel HLA-DRB3*01 variant, HLA-DRB3*0114, containing a DRB1
      sequence motif by micro-temperature gradient gel electrophoresis confirmed by
      sequence-based typing.
AB  - A novel human leukocyte antigen (HLA)-DRB3*01 allele carrying a HLA-DRB1-specific
      sequence motive in exon 2 is described.

PMID- 20030788
TI  - Polymorphisms of cytotoxic T lymphocyte-associated antigen-4 and cytokine genes
      in Taiwanese patients with ankylosing spondylitis.
AB  - Cytokines, costimulatory and counter-regulatory molecules play important roles in
      the regulation of inflammatory response, and are good candidates involved in the
      development of ankylosing spondylitis (AS). This study investigated the genotypic
      distribution of proinflammatory cytokines and T-cell negative regulator cytotoxic
      T lymphocyte-associated antigen-4 (CTLA-4) in healthy subjects and AS patients.
      Genomic DNA was extracted from 143 AS patients and 166 ethnic-matched healthy
      subjects. Nine polymorphisms within the genes of interleukin-4 (IL-4) (-34T>C, 
      81A>G, -285C>T and -589T>C), interleukin-6 (IL-6) (-174G>C), interleukin-10 (IL
      10) (-592A>C and -819T>C) and CTLA-4 (-318C>T and +49A>G) were examined by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. Significantly less AS patients carried the CTLA-4 high-expressing -318
      T allele (P = 0.040). The CTLA-4 +49A>G genotypes were associated with
      circulatory levels of the inflammatory marker C-reactive protein (CRP) (P =
      0.022). Our study documented the most complete genetic information of Taiwanese
      AS patients. The observations that CTLA-4 +49A>G genotypes are associated with
      circulatory CRP levels and significantly less AS subjects carrying CTLA-4 higher
      secretor -318 T allele suggest the level and regulation of inflammation in AS
      subjects may be pre-determined by and associated with CTLA-4 genotypes.

PMID- 20030789
TI  - Therapeutic efficacy of platelet transfusion in patients with acute leukemia: an
      evaluation of methods.
AB  - BACKGROUND: Clinical effect of platelet (PLT) transfusion is monitored by
      measures of PLT viability (PLT recovery and survival) and functionality. In this
      study we evaluate and compare transfusion effect measures in patients with
      chemotherapy-induced thrombocytopenia due to treatment of acute leukemia. STUDY
      DESIGN AND METHODS: Forty transfusions (28 conventional gamma-irradiated and 12
      pathogen-inactivated photochemical-treated PLT concentrates [PCs]) were
      investigated. PC quality was analyzed immediately before transfusion. Samples
      were collected from thrombocytopenic patients at 1 and 24 hours for PLT
      increments and thromboelastography (TEG) with assessments of bleeding score and
      intertransfusion interval (ITI). Data were analyzed by Spearman's correlation.
      Patient and PC variables influencing the effect of transfusion were analyzed by
      use of a mixed-effects model. RESULTS: PLT dose, storage time, and pathogen
      inactivation correlated with PLT recovery but not with PLT survival (including
      ITI), TEG, or clinical bleeding. Fever was negatively correlated with PLT
      survival but did not affect PLT recovery. After 1 and 24 hours, strong
      correlations were observed within measures of PLT viability and between PLT
      increment and the TEG value maximal amplitude (MA). Negative correlation was
      observed between late MA increment and clinical bleeding status after transfusion
      (r = -0.494, p = 0.008). PLT count increments did not correlate to clinical
      bleeding status. CONCLUSIONS: PLT dose and quality of PCs are important for
      optimal immediate transfusion response, whereas duration of transfusion effect is
      influenced mainly by patient variables. The TEG value MA correlates with PLT
      count increments and bleeding, thus reflecting both PLT viability and
      functionality.

PMID- 20030790
TI  - Calcium is a key constituent for maintaining the in vitro properties of platelets
      suspended in the bicarbonate-containing additive solution M-sol with low plasma
      levels.
AB  - BACKGROUND: Commercially available additive solutions (ASs) require 30% to 35%
      plasma for optimal storage of platelets (PLTs). PLTs suspended in M-sol, a
      bicarbonate-based experimental platelet additive solution (PAS), maintain in
      vitro PLT properties during storage with low levels of plasma (< or =5%). STUDY
      DESIGN AND METHODS: Four different formulations of M-sol were prepared at the
      optimal pH (6.1): M-sol, M-sol without calcium, M-sol without citric acid, and M
      sol without calcium and citric acid. Apheresis PLT units (100% plasma) were
      equally divided into five 50-mL aliquots in PL732 containers, centrifuged, and
      resuspended to prepare units suspended in the four different PASs (95%) with 5%
      plasma and 1 unit in 100% plasma. Units (n = 10) were stored under standard
      conditions and assayed for in vitro properties on Days 1, 5, and 7. The data were
      analyzed by analysis of variance for repeated measures (n = 10, p < 0.001).
      RESULTS: On Day 5 of storage, PLTs suspended in the M-sol formulation containing
      calcium but lacking citric acid had similar pH, extent of shape change (ESC)
      values, and percentage of CD62-positive PLTs and greater hypotonic shock response
      (HSR) and percentage of discoid PLTs compared to those of PLTs suspended in 100%
      plasma. In contrast, PLTs suspended in the M-sol formulation lacking calcium had
      lesser ESC values, greater percentage of CD62-positive PLTs, and similar HSR
      values and percentage of discoid PLTs compared to those of PLTs suspended in 100%
      plasma on Day 5 (p < 0.001). CONCLUSIONS: Calcium plays an important role in
      maintaining CD62-negative PLTs and relatively high ESC in 5% plasma. The removal
      of citric acid from M-sol may improve PLT storage properties with low plasma
      levels.

PMID- 20030791
TI  - Evaluation of the Mirasol pathogen [corrected] reduction technology system
      against Babesia microti in apheresis platelets and plasma.
AB  - BACKGROUND: Babesia microti is an intraerythrocytic parasite, transmitted
      naturally to humans by infected ixodid ticks, that causes babesiosis. In recent
      years, B. microti has been identified as a growing public health concern that has
      also emerged as a critical blood safety issue in the absence of appropriate
      interventions to reduce transmission by blood transfusion. Thus, we evaluated the
      ability of the Mirasol pathogen reduction technology (PRT; CaridianBCT), which
      uses riboflavin (RB) and ultraviolet (UV) light, to diminish the presence of B.
      microti in apheresis plasma and platelets (PLTs). STUDY DESIGN AND METHODS:
      Apheresis plasma and PLT units were spiked with B. microti-infected hamster blood
      and subsequently treated using the Mirasol PRT system. Control and experimental
      samples were collected at different stages during the treatment process and
      injected into hamsters to detect the presence of viable parasites. Four weeks
      postinoculation, hamster blood was tested for B. microti infection by blood smear
      and real-time polymerase chain reaction analysis. RESULTS: None of the blood
      smears from animals injected with samples from PRT-treated plasma or PLT units
      were positive by microscopy, while all the non-PRT-treated plasma and PLT units
      were demonstrably parasitemic. Parasite load reduction in hamsters ranged between
      4 and 5 log in all PRT-treated units compared to untreated controls. CONCLUSION:
      The data indicate that the use of RB and UV light efficiently reduces the
      presence of viable B. microti in apheresis plasma and PLT products, thereby
      reducing the risk of transfusion-transmitted Babesia potentially associated with
      these products. Based on this observed "proof of principle," future studies will
      determine the efficacy of the Mirasol PRT in whole blood.

PMID- 20030792
TI  - The first case of alloantibody against human platelet antigen-15b in Japan:
      possible alloimmunization by a hydatidiform mole.
AB  - BACKGROUND: The involvement of the human platelet antigen (HPA)-15 system in
      neonatal alloimmune thrombocytopenia (NAIT) has been reported in various
      populations, but not in the Japanese population. In Japan, the mixed passive
      hemagglutination assay (MPHA) is used for detection of HPA alloantibodies.
      However, most of the reported cases of HPA-15 incompatibility are based on the
      monoclonal antibody immobilization of platelet antigen (MAIPA) assay or
      immunoprecipitation; thus there is a possibility that HPA-15 alloantibodies are
      not efficiently detected by the MPHA, and currently, the causative antibody is
      not detectable in approximately half of the suspected NAIT cases in Japan. STUDY
      DESIGN AND METHODS: We examined the sera of mothers from NAIT cases, previously
      with undetected HPA antibodies by MPHA, using the MAIPA technique. Sera from 90
      mothers of suspected NAIT were tested by MAIPA for the presence of anti-HPA-15
      alloantibodies. RESULTS: Anti-HPA-15b was detected in one case. This case was a
      mother in the first pregnancy diagnosed as hydatid mole-coexisting fetus, and the
      baby was born with suspected NAIT. The familial analysis revealed compatibility
      of HPA-15 genotype between the mother and the baby (both HPA-15a/a), but
      incompatibility with the paternal one (HPA-15a/b). The hydatid mole's tissue was
      genotyped as HPA-15b positive. Besides anti-HPA-15b, maternal sera contain strong
      HLA Class I antibody CONCLUSIONS: Here we reported the first case of anti-HPA-15
      in Japan. Alloimmunization against the hydatid mole seems to be responsible for
      the production of HPA-15b alloantibody. This antibody, however, did not
      apparently involve in the development of NAIT of the newborn, the coexisting anti
      HLA Class I being the possible cause.

PMID- 20030793
TI  - Hypothesis testing in clinical and basic science research.

PMID- 20030794
TI  - Acute cellular rejection and Epstein-Barr virus-related post-transplant
      lymphoproliferative disorder in a pediatric lung transplant with low viral load.
AB  - We report the case of an 18-year-old male who underwent bilateral lung
      transplantation for end-stage cystic fibrosis. No Epstein-Barr virus (EBV) or
      cytomegalovirus serology mismatch was detected on pre-transplant evaluation
      (donor and recipient were both positive). Two months after lung transplantation a
      computed tomography scan showed multiple nodules throughout both lungs. At that
      time a low EBV DNA blood level was detected (<300 copies/100,000
      lymphomonocytes). Scheduled follow-up transbronchial biopsy (TBB) revealed a
      prevalent finding characterized by perivascular lymphoid infiltrates with
      endothelitis. Extensive tissue coagulative necrosis with peripheral areas of
      dense aggregates of larger lymphoid cells were detected in the trans-thoracic
      fine needle core biopsy (FNCB) performed on the largest nodule. The
      immunophenotypic profile characterized the perivascular lymphoid cells in TBB as
      mainly composed of T lymphocytes (CD3 positive) while the larger number of
      lymphocytes in FNCB as B cells (CD20 positive). In situ hybridization for EBV
      (EBER mRNA) was negative in TBB while it was positive in many lymphocytes of the
      FNCB. Real-time polymerase chain reaction (PCR) for EBV was performed on paraffin
      embedded FNCB and detected a high quantity of EBV genomes (1260 copies/cell). IgH
      gene rearrangement using a fragment size PCR technique revealed a monoclonal B
      cell population in FNCB. Morphological and molecular findings suggest a final
      diagnosis of acute cellular rejection and a post-transplant lymphoproliferative
      disorder (PTLD) EBV-related in a lung transplant recipient with a low EBV DNA
      blood level. A possible coexistence of PTLD and acute rejection should be
      considered both for diagnosis and treatment. EBV PCR in the peripheral blood is a
      useful screening tool in transplant recipients; however, rare cases with PTLD may
      not have detectable levels of EBV DNA. This aspect should be taken into
      consideration to avoid false negatives.

PMID- 20030795
TI  - Herpes simplex virus hepatitis after pediatric liver transplantation.
AB  - Herpes simplex virus (HSV) hepatitis has a fatal impact on the outcome of organ
      transplanted recipients. Here, we present a thought-provoking case of HSV
      hepatitis in a high-risk recipient after living-related liver transplantation
      (LRLT). A 1-month-old female newborn infant was affected by HSV encephalitis.
      Fulminant hepatic failure (FHF) of unknown etiology occurred suddenly at 4.4
      years of age. Viral infections were ruled out as the cause of FHF. Intensive care
      including plasma exchange (PE) was started, and the preoperative treatments for
      ABO incompatibility were performed. Thereafter, LRLT was performed emergently.
      Although strong immunosuppression for ABO incompatibility was continued after
      LRLT, antibody-mediated rejection (AMR) occurred on postoperative day (POD) 4. PE
      was repeated and improvements were obtained. However, liver dysfunction appeared
      on POD 8. Histopathological findings of liver needle biopsy clearly revealed HSV
      hepatitis, although the results of HSV DNA and antibody titer in blood sample did
      not clearly indicate HSV infection. On POD 21, thrombotic microangiopathy (TMA)
      occurred and the plasma and immunoglobulin were replenished. Our pediatric
      recipient recovered successfully from AMR, HSV hepatitis, TMA, and repeated
      sepsis. We conclude that well considered therapy based on the real-time detection
      of HSV hepatitis is indispensable for the further improvements of outcome in HSV
      hepatitis after LRLT.

PMID- 20030796
TI  - Endovascular treatment of hepatic artery thrombosis following liver
      transplantation.
AB  - Hepatic artery thrombosis (HAT) is the most frequent vascular complication
      following orthotopic liver transplantation. Urgent retransplantation has been
      considered as the mainstay therapy. Surgical revascularization is an effective
      alternative in asymptomatic patients. Endovascular therapies including intra
      arterial thrombolysis, percutaneous transluminal angioplasty (PTA), and stent
      placement have shown encouraging results in recent years; however, their use
      remains controversial because of potential risk of hemorrhage. Until June 2009,
      69 cases were published in 16 reports describing therapeutic potential of
      endovascular modalities. Interventions were performed as early as within 4 h to
      as late as 120 days in patients ranging from 4 months to 64 years of age.
      Majority of published reports suggested the use of urokinase. Thrombolysis was
      successful in 47 out of 69 (68%) patients. Bleeding was the most common
      complication including fatal intra-abdominal hemorrhage in three patients. Twenty
      nine out of 47 (62%) patients underwent further intervention in the form of PTA,
      stenting, or both. The follow-up patency ranged from 1 month to 26 months. In
      conclusion, whenever possible, efforts should be made to rescue the liver grafts
      through urgent revascularization (surgical and/or endovascular) depending on
      patient's condition and interventional expertise at the transplant center;
      reserving the option of retransplantation for failure, complications, and cases
      with severe clinical symptoms or allograft dysfunction.

PMID- 20030798
TI  - Expression of oestrogen and progesterone receptors in canine sebaceous gland
      tumours.
AB  - Sebaceous gland oestrogen alpha (ERalpha) and progesterone (PR) receptor
      expression was examined immunohistochemically in 26 and 32 dogs respectively with
      sebaceous gland hyperplasia/adenomas, epitheliomas and carcinomas, and in the
      glands of 10 healthy controls. The mean percentage of ERalpha positive nuclei in
      control sebaceous glands was 21.31% compared with 11.5% in hyperplasia/adenoma
      type lesions, although these values were not statistically different. In
      sebaceous gland epitheliomas and carcinomas, positive basal cells represented
      7.86% and 3.53% of neoplastic cells respectively and these mean percentages were
      significantly lower in epitheliomas (P < 0.024) and carcinomas (P < 0.015) than
      in controls. The mean percentage of PR-positive nuclei in control sebaceous
      glands was 23.96%, similar to the 22.07% found in hyperplasia/adenoma-type
      lesions. In sebaceous gland epitheliomas and carcinomas, positive cells were
      scarce and represented 13.5% and 4.06% of neoplastic cells respectively.
      Differences in the percentage of positive cells between normal and pathological
      glands reached statistical significance for carcinomas (P < 0.043). In the
      control group there was greater PR (P < 0.001) and ERalpha expression (P < 0.014)
      in sebaceous glands in female dogs. The PR and ERalpha immunoreactivity in each
      category of neoplastic lesions could not be analysed because sample size was too
      small but when all the sebaceous gland tumours were grouped and analysed, no sex
      difference was found. The results suggest that oestrogen and progesterone
      receptor expression is reduced in some canine sebaceous gland tumours. These
      changes may represent a contributing factor for tumour growth or simply be a
      consequence of tumour progression.

PMID- 20030799
TI  - In vitro antimicrobial activity of a commercial ear antiseptic containing
      chlorhexidine and Tris-EDTA.
AB  - Minimum bactericidal concentrations (MBCs) of a commercial ear antiseptic
      containing chlorhexidine 0.15% and Tris-EDTA (Otodine) were determined by broth
      microdilution for 150 isolates representing the most common pathogens associated
      with canine otitis. The microorganisms were classified into three groups
      according to their levels of susceptibility. The most susceptible group included
      Staphylococcus pseudintermedius, Malassezia pachydermatis, Streptococcus canis
      and Corynebacterium auriscanis, which were generally killed by 1 : 64 dilution of
      the antiseptic product (MBC = 23/0.8 microg/mL of chlorhexidine/Tris-EDTA). The
      most resistant organism was Proteus mirabilis, which survived up to 1 : 8
      dilution of the product (MBC = 375/12 microg/mL). Escherichia coli, Pseudomonas
      aeruginosa and Staphylococcus aureus displayed intermediate MBCs ranging between
      188/6 and 47/1.5 microg/mL. Interestingly, S. pseudintermedius was more
      susceptible than S. aureus, and no significant difference was observed between
      meticillin-resistant and meticillin-susceptible isolates within each species,
      indicating that antiseptic use is unlikely to co-select for meticillin
      resistance. Although the concentrations required for killing (MBCs) varied
      considerably with microorganism type, the combination of chlorhexidine 0.15% and
      Tris-EDTA was active against all the pathogens most commonly involved in canine
      otitis.

PMID- 20030800
TI  - Copia and Gypsy retrotransposons activity in sunflower (Helianthus annuus L.).
AB  - BACKGROUND: Retrotransposons are heterogeneous sequences, widespread in
      eukaryotic genomes, which refer to the so-called mobile DNA. They resemble
      retroviruses, both in their structure and for their ability to transpose within
      the host genome, of which they make up a considerable portion. Copia- and Gypsy
      like retrotransposons are the two main classes of retroelements shown to be
      ubiquitous in plant genomes. Ideally, the retrotransposons life cycle results in
      the synthesis of a messenger RNA and then self-encoded proteins to process
      retrotransposon mRNA in double stranded extra-chromosomal cDNA copies which may
      integrate in new chromosomal locations. RESULTS: The RT-PCR and IRAP protocol
      were applied to detect the presence of Copia and Gypsy retrotransposon
      transcripts and of new events of integration in unstressed plants of a sunflower
      (Helianthus annuus L.) selfed line. Results show that in sunflower
      retrotransposons transcription occurs in all analyzed organs (embryos, leaves,
      roots, and flowers). In one out of sixty-four individuals analyzed,
      retrotransposons transcription resulted in the integration of a new element into
      the genome. CONCLUSION: These results indicate that the retrotransposon life
      cycle is firmly controlled at a post transcriptional level. A possible silencing
      mechanism is discussed.

PMID- 20030801
TI  - Leptin and Adiponectin: new players in the field of tumor cell and leukocyte
      migration.
AB  - Adipose tissue is no longer considered to be solely an energy storage, but exerts
      important endocrine functions, which are primarily mediated by a network of
      various soluble factors derived from fat cells, called adipocytokines. In
      addition to their responsibility to influence energy homeostasis, new studies
      have identified important pathways linking metabolism with the immune system, and
      demonstrating a modulatory role of adipocytokines in immune function.
      Additionally, epidemiological studies underline that obesity represents a
      significant risk factor for the development of cancer, although the exact
      mechanism of this relationship remains to be determined. Whereas a possible
      influence of adipocytokines on the proliferation of tumor cells is already known,
      new evidence has come to light elucidating a modulatory role of this signaling
      substances in the regulation of migration of leukocytes and tumor cells. The
      migration of leukocytes is a key feature to fight cancer cells, whereas the
      locomotion of tumor cells is a prerequisite for tumor formation and metastasis.
      We herein review the latest tumor biological findings on the role of the most
      prominent adipocytokines leptin and adiponectin, which are secreted by fat cells,
      and which are involved in leukocyte migration, tumor growth, invasion and
      metastasis. This review thus accentuates the complex, interactive involvement of
      adipocytokines in the regulation of migration of both leukocytes and tumor cells,
      and gives an insight in the underlying molecular mechanisms.

PMID- 20030802
TI  - Effects of acute hypoventilation and hyperventilation on exhaled carbon monoxide
      measurement in healthy volunteers.
AB  - BACKGROUND: High levels of exhaled carbon monoxide (eCO) are a marker of airway
      or lung inflammation. We investigated whether hypo- or hyperventilation can
      affect measured values. METHODS: Ten healthy volunteers were trained to achieve
      sustained end-tidal CO2 (etCO(2)) concentrations of 30 (hyperventilation), 40
      (normoventilation), and 50 mmHg (hypoventilation). As soon as target etCO(2)
      values were achieved for 120 sec, exhaled breath was analyzed for eCO with a
      photoacoustic spectrometer. At etCO(2) values of 30 and 40 mmHg exhaled breath
      was sampled both after a deep inspiration and after a normal one. All
      measurements were performed in two different environmental conditions: A) ambient
      CO concentration = 0.8 ppm and B) ambient CO concentration = 1.7 ppm. RESULTS:
      During normoventilation, eCO mean (standard deviation) was 11.5 (0.8) ppm; it
      decreased to 10.3 (0.8) ppm during hyperventilation (p < 0.01) and increased to
      11.9 (0.8) ppm during hypoventilation (p < 0.01). eCO changes were less
      pronounced than the correspondent etCO(2) changes (hyperventilation: 10% Vs 25%
      decrease; hypoventilation 3% Vs 25% increase). Taking a deep inspiration before
      breath sampling was associated with lower eCO values (p < 0.01), while
      environmental CO levels did not affect eCO measurement. CONCLUSIONS: eCO
      measurements should not be performed during marked acute hyperventilation, like
      that induced in this study, but the influence of less pronounced hyperventilation
      or of hypoventilation is probably negligible in clinical practice.

PMID- 20030803
TI  - Effects of temperature on gene expression in embryos of the coral Montastraea
      faveolata.
AB  - BACKGROUND: Coral reefs are expected to be severely impacted by rising seawater
      temperatures associated with climate change. This study used cDNA microarrays to
      investigate transcriptional effects of thermal stress in embryos of the coral
      Montastraea faveolata. Embryos were exposed to 27.5 degrees C, 29.0 degrees C,
      and 31.5 degrees C directly after fertilization. Differences in gene expression
      were measured after 12 and 48 hours. RESULTS: Analysis of differentially
      expressed genes indicated that increased temperatures may lead to oxidative
      stress, apoptosis, and a structural reconfiguration of the cytoskeletal network.
      Metabolic processes were downregulated, and the action of histones and zinc
      finger-containing proteins may have played a role in the long-term regulation
      upon heat stress. CONCLUSIONS: Embryos responded differently depending on
      exposure time and temperature level. Embryos showed expression of stress-related
      genes already at a temperature of 29.0 degrees C, but seemed to be able to
      counteract the initial response over time. By contrast, embryos at 31.5 degrees C
      displayed continuous expression of stress genes. The genes that played a role in
      the response to elevated temperatures consisted of both highly conserved and
      coral-specific genes. These genes might serve as a basis for research into coral
      specific adaptations to stress responses and global climate change.

PMID- 20030804
TI  - BAC array CGH in patients with Velocardiofacial syndrome-like features reveals
      genomic aberrations on chromosome region 1q21.1.
AB  - BACKGROUND: Microdeletion of the chromosome 22q11.2 region is the most common
      genetic aberration among patients with velocardiofacial syndrome (VCFS) but a
      subset of subjects do not show alterations of this chromosome region. METHODS: We
      analyzed 18 patients with VCFS-like features by comparative genomic hybridisation
      (aCGH) array and performed a face-to-face slide hybridization with two different
      arrays: a whole genome and a chromosome 22-specific BAC array. Putative
      rearrangements were confirmed by FISH and MLPA assays. RESULTS: One patient
      carried a combination of rearrangements on 1q21.1, consisting in a
      microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously
      reported in patients with variable phenotypes, including mental retardation,
      congenital heart defects (CHD) and schizophrenia. While 326 control samples were
      negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212
      kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected
      four copy number variants (CNVs) inherited from one parent (a 744-kb duplication
      on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a
      gain of 140 kb on 22q13.2), not present in control subjects, raising the
      potential role of these CNVs in the VCFS-like phenotype. CONCLUSIONS: Our results
      confirmed aCGH as a successful strategy in order to characterize additional
      submicroscopic aberrations in patients with VCF-like features that fail to show
      alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1,
      detected in two patients, which may contribute to CHD.

PMID- 20030805
TI  - Cooperation of Notch and Ras/MAPK signaling pathways in human breast
      carcinogenesis.
AB  - BACKGROUND: Recent studies have implicated aberrant Notch signaling in breast
      cancers. Yet, relatively little is known about the pattern of expression of
      various components of the Notch pathway, or its mechanism of action. To better
      understand the role of the Notch pathway in breast cancer, we have undertaken a
      detailed expression analysis of various Notch receptors, their ligands, and
      downstream targets at different stages of breast cancer progression. RESULTS: We
      report here that there is a general increase in the expression levels of Notch 1,
      2, 4, Jagged1, Jagged2, and Delta-like 4 proteins in breast cancers, with
      simultaneous upregulation of multiple Notch receptors and ligands in a given
      cancer tissue. While Notch3 and Delta-like1 were undetectable in normal tissues,
      moderate to high expression was detected in several cancers. We detected the
      presence of active, cleaved Notch1, along with downstream targets of the Notch
      pathway, Hes1/Hes5, in approximately 75% of breast cancers, clearly indicating
      that in a large proportion of breast cancers Notch signaling is aberrantly
      activated. Furthermore, we detected cleaved Notch1 and Hes1/5 in early precursors
      of breast cancers - hyperplasia and ductal carcinoma in situ - suggesting that
      aberrant Notch activation may be an early event in breast cancer progression.
      Mechanistically, while constitutively active Notch1 alone failed to transform
      immortalized breast cells, it synergized with the Ras/MAPK pathway to mediate
      transformation. This cooperation is reflected in vivo, as a subset of cleaved
      Notch positive tumors additionally expressed phopsho-Erk1/2 in the nuclei. Such
      cases exhibited high node positivity, suggesting that Notch-Ras cooperation may
      lead to poor prognosis. CONCLUSIONS: High level expression of Notch receptors and
      ligands, and its increased activation in several breast cancers and early
      precursors, places Notch signaling as a key player in breast cancer pathogenesis.
      Its cooperation with the Ras/MAPK pathway in transformation offers combined
      inhibition of the two pathways as a new modality for breast cancer treatment.

PMID- 20030806
TI  - Helicobacter pylori infection is associated with decreased serum levels of high
      density lipoprotein, but not with the severity of coronary atherosclerosis.
AB  - OBJECTIVE: The objective of this survey was to study the association between
      Helicobacter pylori infection and the severity of coronary atherosclerosis.
      METHODS: The study population consisted of 961 consecutive patients (711 males
      and 250 females) who underwent coronary angiography for suspected or known
      coronary atherosclerosis. The patients' body mass index, blood pressure, the
      blood lipid, blood glucose, leukocyte count (10(9)/L), neutrophil count
      (10(9)/L), and Helicobacter pylori-specific IgG antibodies were performed.
      Coronary angiograms were scored according to vessel score and Gensini's score.
      RESULTS: A significant association between H. pylori infection and coronary
      atherosclerosis as well as its severity was not find in this cross section study
      (p = 0.858). And, the level distribution of vessel score (p = 0.906) and
      Gensini's score (p = 0.905) were similar in the seropositivity group and
      seronegativity group of Helicobacter pylori infection. However, the level of
      fasting high-density lipoprotein cholesterol (mmol/L) (p = 0.013) was
      significantly lower in the seropositivity group than that in the seronegativity
      group of Helicobacter pylori infection. CONCLUSIONS: In conclusion, in the
      present study, a significantly correlation between Helicobacter pylori
      seropositivity and angiographically evaluated severity of atherosclerosis was not
      find. And, the present study showed a good correlation between Helicobacter
      pylori infection and decreased HDL cholesterol. However, the exact mechanisms
      need further study.

PMID- 20030807
TI  - MultiTest V.1.2, a program to binomially combine independent tests and
      performance comparison with other related methods on proportional data.
AB  - BACKGROUND: Combining multiple independent tests, when all test the same
      hypothesis and in the same direction, has been the subject of several approaches.
      Besides the inappropriate (in this case) Bonferroni procedure, the Fisher's
      method has been widely used, in particular in population genetics. This last
      method has nevertheless been challenged by the SGM (symmetry around the geometric
      mean) and Stouffer's Z-transformed methods that are less sensitive to asymmetry
      and deviations from uniformity of the distribution of the partial P-values.
      Performances of these different procedures were never compared on proportional
      data such as those currently used in population genetics. RESULTS: We present new
      software that implements a more recent method, the generalised binomial
      procedure, which tests for the deviation of the observed proportion of P-values
      lying under a chosen threshold from the expected proportion of such P-values
      under the null hypothesis. The respective performances of all available
      procedures were evaluated using simulated data under the null hypothesis with
      standard P-values distribution (differentiation tests). All procedures more or
      less behaved consistently with approximately 5% significant tests at alpha =
      0.05. Then, linkage disequilibrium tests with increasing signal strength (rate of
      clonal reproduction), known to generate highly non-standard P-value distributions
      are undertaken and finally real population genetics data are analysed. In these
      cases, all procedures appear, more or less equally, very conservative, though SGM
      seems slightly more conservative. CONCLUSION: Based on our results and those
      discussed in the literature we conclude that the generalised binomial and
      Stouffer's Z procedures should be preferred and Z when the number of tests is
      very small. The more conservative SGM might still be appropriate for meta
      analyses when a strong publication bias in favour of significant results is
      expected to inflate type 2 error.

PMID- 20030808
TI  - Helicobacter pylori--a seasoned pathogen by any other name.
AB  - Helicobacter pylori is a well known inhabitant of human stomach which is linked
      to peptic ulcer disease and gastric adenocarcinoma. It was recently shown in
      several studies that H. pylori can be harnessed as a surrogate marker of human
      migration and that its population structure and stratification patterns exactly
      juxtapose to those of Homo sapiens. This is enough a testimony to convey that H.
      pylori may have coevolved with their host. Several protective effects of H.
      pylori colonization have been considered as evidence of a presumed symbiotic
      relationship. Contrary to this assumption is the presence of a strong virulence
      apparatus within H. pylori; why a co-evolved parasite would try inflicting its
      host with serious infection and even causing cancer? The answer is perhaps
      embedded in the evolutionary history of both the bacterium and the host. We
      discuss a hypothetical scenario wherein H. pylori may have acquired virulence
      genes from donors within its environment that varied with change in human history
      and ecology. The H. pylori genomes sequenced to date portray fairly high
      abundance of such laterally acquired genes which have no assigned functions but
      could be linked to inflammatory responses or other pathogenic attributes.
      Therefore, the powerful virulence properties and survival strategies of
      Helicobacter make it a seasoned pathogen; thus the efforts to portray it as a
      commensal or a (harmless) 'bacterial parasite' need rethinking.

PMID- 20030809
TI  - Conservation of DNA-binding specificity and oligomerisation properties within the
      p53 family.
AB  - BACKGROUND: Transcription factors activate their target genes by binding to
      specific response elements. Many transcription factor families evolved from a
      common ancestor by gene duplication and subsequent divergent evolution. Members
      of the p53 family, which play key roles in cell-cycle control and development,
      share conserved DNA binding and oligomerisation domains but exhibit distinct
      functions. In this study, the molecular basis of the functional divergence of
      related transcription factors was investigated. RESULTS: We characterised the DNA
      binding specificity and oligomerisation properties of human p53, p63 and p73, as
      well as p53 from other organisms using novel biophysical approaches. All p53
      family members bound DNA cooperatively as tetramers with high affinity. Despite
      structural differences in the oligomerisation domain, the dissociation constants
      of the tetramers was in the low nanomolar range for all family members,
      indicating that the strength of tetramerisation was evolutionarily conserved.
      However, small differences in the oligomerisation properties were observed, which
      may play a regulatory role. Intriguingly, the DNA-binding specificity of p53
      family members was highly conserved even for evolutionarily distant species.
      Additionally, DNA recognition was only weakly affected by CpG methylation.
      Prediction of p53/p63/p73 binding sites in the genome showed almost complete
      overlap between the different homologs. CONCLUSION: Diversity of biological
      function of p53 family members is not reflected in differences in sequence
      specific DNA binding. Hence, additional specificity factors must exist, which
      allowed the acquisition of novel functions during evolution while preserving
      original roles.

PMID- 20030811
TI  - The Colombian conflict: a description of a mental health program in the
      Department of Tolima.
AB  - Colombia has been seriously affected by an internal armed conflict for more than
      40 years affecting mainly the civilian population, who is forced to displace,
      suffers kidnapping, extortion, threats and assassinations. Between 2005 and 2008,
      Medecins Sans Frontieres-France provided psychological care and treatment in the
      region of Tolima, a strategic place in the armed conflict. The mental health
      program was based on a short-term multi-faceted treatment developed according to
      the psychological and psychosomatic needs of the population. Here we describe the
      population attending during 2005-2008, in both urban and rural settings, as well
      as the psychological treatment provided during this period and its outcomes.We
      observed differences between the urban and rural settings in the traumatic events
      reported, the clinical expression of the disorders, the disorders diagnosed, and
      their severity. Although the duration of the treatment was limited due to
      security reasons and access difficulties, patient condition at last visit
      improved in most of the patients. These descriptive results suggest that further
      studies should be conducted to examine the role of short-term psychotherapy,
      adapted specifically to the context, can be a useful tool to provide
      psychological care to population affected by an armed conflict.

PMID- 20030810
TI  - Hypothermia in bleeding trauma: a friend or a foe?
AB  - The induction of hypothermia for cellular protection is well established in
      several clinical settings. Its role in trauma patients, however, is
      controversial. This review discusses the benefits and complications of induced
      hypothermia--emphasizing the current state of knowledge and potential
      applications in bleeding patients. Extensive pre-clinical data suggest that in
      advanced stages of shock, rapid cooling can protect cells during ischemia and
      reperfusion, decrease organ damage, and improve survival. Yet hypothermia is a
      double edged sword; unless carefully managed, its induction can be associated
      with a number of complications. Appropriate patient selection requires a thorough
      understanding of the pre-clinical literature. Clinicians must also appreciate the
      enormous influence that temperature modulation exerts on various cellular
      mechanisms. This manuscript aims to provide a balanced view of the published
      literature on this topic. While many of the advantageous molecular and
      physiological effects of induced hypothermia have been outlined in animal models,
      rigorous clinical investigations are needed to translate these promising findings
      into clinical practice.

PMID- 20030812
TI  - MTHFR C677T and postmenopausal breast cancer risk by intakes of one-carbon
      metabolism nutrients: a nested case-control study.
AB  - INTRODUCTION: The C677T polymorphism of the methylenetetrahydrofolate reductase
      (MTHFR) gene has been hypothesized to increase breast cancer risk. However,
      results have been inconsistent, and few studies have reported the association by
      menopausal status or by intakes of nutrients participating in one-carbon
      metabolism. Our aims were to investigate whether MTHFR C677T was associated with
      postmenopausal breast cancer risk and whether this relation was modified by
      intakes of folate, methionine, vitamins B(2), B(6), and B(12), and alcohol.
      METHODS: We studied 318 incident breast cancer cases and 647 age- and race
      matched controls participating in a nested case-control study of postmenopausal
      women within the VITamins And Lifestyle (VITAL) cohort. Genotyping was conducted
      for MTHFR C677T and dietary and supplemental intakes were ascertained from a
      validated questionnaire. Adjusted odds ratios (OR) and 95% confidence intervals
      (CI) were calculated using unconditional logistic regression. RESULTS: We
      observed a 62% increased risk of breast cancer among postmenopausal women with
      the TT genotype (OR = 1.62; 95% CI: 1.05 to 2.48). Women with a higher number of
      variant T alleles had higher risk of breast cancer (P for trend = 0.04). Evidence
      of effect-modification by intakes of some B vitamins was observed. The most
      pronounced MTHFR-breast cancer risks were observed among women with the lowest
      intakes of dietary folate (P for interaction = 0.02) and total (diet plus
      supplemental) vitamin B(6) (P for interaction = 0.01), with no significant
      increased risks among women with higher intakes. CONCLUSIONS: This study provides
      support that the MTHFR 677TT genotype is associated with a moderate increase in
      risk of postmenopausal breast cancer and that this risk may be attenuated with
      high intakes of some one-carbon associated nutrients.

PMID- 20030813
TI  - The use of mobile phones as a data collection tool: a report from a household
      survey in South Africa.
AB  - BACKGROUND: To investigate the feasibility, the ease of implementation, and the
      extent to which community health workers with little experience of data
      collection could be trained and successfully supervised to collect data using
      mobile phones in a large baseline survey METHODS: A web-based system was
      developed to allow electronic surveys or questionnaires to be designed on a word
      processor, sent to, and conducted on standard entry level mobile phones. RESULTS:
      The web-based interface permitted comprehensive daily real-time supervision of
      CHW performance, with no data loss. The system permitted the early detection of
      data fabrication in combination with real-time quality control and data collector
      supervision. CONCLUSIONS: The benefits of mobile technology, combined with the
      improvement that mobile phones offer over PDA's in terms of data loss and
      uploading difficulties, make mobile phones a feasible method of data collection
      that needs to be further explored.

PMID- 20030814
TI  - The emerging dental workforce: long-term career expectations and influences. A
      quantitative study of final year dental students' views on their long-term career
      from one London Dental School.
AB  - BACKGROUND: Research into the motivation and expectations of the emerging
      workforce and their short-term expectations has already been reported with a view
      to informing professional and policy decisions. The objective of this component
      of the research programme was to examine the long-term goals and perceived
      influences on final year dental students' professional careers. METHODS:
      Univariate analysis of a self completed questionnaire survey of all final year
      dental students from King's College London, comprising questions on demography,
      long-term career goals and influences, proposed commitment to dentistry,
      commitment to healthcare systems and the influences thereon. Statistical analysis
      included Chi Squared tests for linear association. RESULTS: Ninety per cent of
      students responded to this survey (n = 126), the majority of whom were aged 23
      years (59%), female (58%) and Asian (70%). Long-term career goals were fairly
      evenly split between 'dentist with a special interest' (27%), 'primary dental
      care practitioner' (26%) and 'specialist' (25%), with 19% not certain. Only 60%
      of total respondents anticipated working full-time in the long-term (79% males cf
      52% females; p = 0.00). The vast majority of respondents (> or =80%) identified
      'work-life balance', 'financial stability' and 'professional development' as
      'important' or 'very important' influences on the number of future sessions.
      Females were significantly more likely to rate childcare commitments as an
      important influence on their future working capacity compared with males (p =
      0.00). A wide range of factors were considered important or very important in
      making the NHS attractive, led by support for professional development (88%) and
      feeling valued by patients (88%), as well as funding, time with patients, rewards
      for prevention and practical issues such as dental materials and premises.
      Females were significantly more likely than males to be attracted to work within
      the NHS by 'childcare support' (p = 0.02), 'retraining facilities after career
      break' (p = 0.01), 'assistance with student debt' (p = 0.01) and 'incentives to
      work in deprived areas'. CONCLUSION: Long-term career plans of new graduates from
      this London Dental School commonly embrace opportunities for professional
      development as well as personal issues such as work/life balance and financial
      income. Significant differences were identified between male and females long
      term plans and influences. The implications of these findings are discussed.

PMID- 20030815
TI  - PLCL1 rs7595412 variation is not associated with hip bone size variation in
      postmenopausal Danish women.
AB  - BACKGROUND: Bone size (BS) variation is under strong genetic control and plays an
      important role in determining bone strength and fracture risk. Recently, a genome
      wide association study identified polymorphisms associated with hip BS variation
      in the PLCL1 (phospholipase c-like 1) locus. Carriers of the major A allele of
      the most significant polymorphism, rs7595412, have around 17% larger hip BS than
      non-carriers. We therefore hypothesized that this polymorphism may also influence
      postmenopausal complications. METHODS: The effects of rs7595412 on hip BS, bone
      mineral density (BMD), vertebral fractures, serum Crosslaps and osteocalcin
      levels were analyzed in 1,191 postmenopausal Danish women. RESULTS: This
      polymorphism had no influence on hip and spine BS as well as on femur and spine
      BMD. Women carrying at least one copy of the A allele had lower levels of serum
      osteocalcin as compared with those homozygous for the G allele (p = 0.03) whereas
      no effect on serum Crosslaps was detected. Furthermore, women homozygous for the
      A allele were more affected by vertebral fractures than those carrying at least
      one copy of the G allele (p = 0.04). CONCLUSIONS: In postmenopausal women, our
      results suggest that the PLCL1 rs7595412 polymorphism has no obvious effect on
      hip BS or BMD but may be nominally associated with increased proportion of
      vertebral fracture and increased levels of osteocalcin.

PMID- 20030816
TI  - Active immunization to tumor necrosis factor-alpha is effective in treating
      chronic established inflammatory disease: a long-term study in a transgenic model
      of arthritis.
AB  - INTRODUCTION: Passive blockade of tumor necrosis factor-alpha (TNF-alpha) has
      demonstrated high therapeutic efficiency in chronic inflammatory diseases, such
      as rheumatoid arthritis, although some concerns remain such as occurrence of
      resistance and high cost. These limitations prompted investigations of an
      alternative strategy to target TNF-alpha. This study sought to demonstrate a long
      lasting therapeutic effect on established arthritis of an active immunotherapy to
      human (h) TNF-alpha and to evaluate the long-term consequences of an endogenous
      anti-TNF-alpha response. METHODS: hTNF-alpha transgenic mice, which spontaneously
      develop arthritides from 8 weeks of age, were immunized with a heterocomplex (TNF
      kinoid, or TNF-K) composed of hTNF-alpha and keyhole limpet hemocyanin after
      disease onset. We evaluated arthritides by clinical and histological assessment,
      and titers of neutralizing anti-hTNF-alpha antibody by enzyme-linked
      immunosorbent assay and L929 assay. RESULTS: Arthritides were dramatically
      improved compared to control mice at week 27. TNF-K-treated mice exhibited high
      levels of neutralizing anti-hTNF-alpha antibodies. Between weeks 27 and 45, all
      immunized mice exhibited symptoms of clinical deterioration and a parallel
      decrease in anti-hTNF-alpha neutralizing antibodies. A maintenance dose of TNF-K
      reversed the clinical deterioration and increased the anti-hTNF-alpha antibody
      titer. At 45 weeks, TNF-K long-term efficacy was confirmed by low clinical and
      mild histological scores for the TNF-K-treated mice. Injections of unmodified
      hTNF-alpha did not induce a recall response to hTNF-alpha in TNF-K immunized
      mice. CONCLUSIONS: Anti-TNF-alpha immunotherapy with TNF-K has a sustained but
      reversible therapeutic efficacy in an established disease model, supporting the
      potential suitability of this approach in treating human disease.

PMID- 20030817
TI  - Nine years experience in surgical approach of leiomyomatosis of esophagus.
AB  - BACKGROUND: Leiomyomas of esophagus, although rare, are the most frequent benign
      tumors of esophagus. Aim of this study is the presentation of 7 patients with
      esophageal leiomyomas who underwent surgical treatment during a 9-year period.
      METHODS: Epidemiological data (sex, age), the presenting symptoms, diagnostic
      examinations, tumor location, histopathological findings and the safety and
      efficacy of surgical resection are analyzed and assessed. RESULTS: 5 men and 2
      women with mean age of 56.9 years were operated. In 3 cases the tumor was located
      at the lower esophagus, while in the other 4 cases, the leiomyoma was found at
      the median third of esophagus. 4 patients had severe symptoms related to the
      leiomyoma, such as dysphagia and epigastric pain. All patients underwent a right
      postolateral thoracotomy with enucleation of the lesion. None of them received
      resection of part of the esophagus. The mean diameter of the resected tumors was
      4.3 cm. The dimensions of leiomyomas were immediately associated with the
      symptoms. In no case was detected malignancy or recurrence. All patients were
      relieved from their symptoms, while postoperative morbidity and mortality did not
      occur. CONCLUSIONS: Esophageal leiomyoma is a benign tumor, which causes symptoms
      only if its size becomes large. Surgical enucleation is considered to be safe and
      effective, without complications.

PMID- 20030818
TI  - IRIS: a method for reverse engineering of regulatory relations in gene networks.
AB  - BACKGROUND: The ultimate aim of systems biology is to understand and describe how
      molecular components interact to manifest collective behaviour that is the sum of
      the single parts. Building a network of molecular interactions is the basic step
      in modelling a complex entity such as the cell. Even if gene-gene interactions
      only partially describe real networks because of post-transcriptional
      modifications and protein regulation, using microarray technology it is possible
      to combine measurements for thousands of genes into a single analysis step that
      provides a picture of the cell's gene expression. Several databases provide
      information about known molecular interactions and various methods have been
      developed to infer gene networks from expression data. However, network topology
      alone is not enough to perform simulations and predictions of how a molecular
      system will respond to perturbations. Rules for interactions among the single
      parts are needed for a complete definition of the network behaviour. Another
      interesting question is how to integrate information carried by the network
      topology, which can be derived from the literature, with large-scale experimental
      data. RESULTS: Here we propose an algorithm, called inference of regulatory
      interaction schema (IRIS), that uses an iterative approach to map gene expression
      profile values (both steady-state and time-course) into discrete states and a
      simple probabilistic method to infer the regulatory functions of the network.
      These interaction rules are integrated into a factor graph model. We test IRIS on
      two synthetic networks to determine its accuracy and compare it to other methods.
      We also apply IRIS to gene expression microarray data for the Saccharomyces
      cerevisiae cell cycle and for human B-cells and compare the results to literature
      findings. CONCLUSIONS: IRIS is a rapid and efficient tool for the inference of
      regulatory relations in gene networks. A topological description of the network
      and a matrix of gene expression profiles are required as input to the algorithm.
      IRIS maps gene expression data onto discrete values and then computes regulatory
      functions as conditional probability tables. The suitability of the method is
      demonstrated for synthetic data and microarray data. The resulting network can
      also be embedded in a factor graph model.

PMID- 20030819
TI  - Basal cell adenocarcinoma of a hard palate minor salivary gland: case report and
      review of the literature.
AB  - OBJECTIVE: Basal cell adenocarcinoma of a minor salivary gland is extremely rare.
      The goal of this report is to increase awareness of this rare disease and to
      review and discuss the differential diagnosis and important considerations in
      treatment. STUDY DESIGN: Case report and review of the literature. METHODS: Case
      report of a basal cell adenocarcinoma of a hard palate minor salivary gland and
      review of the literature of basal cell adenocarcinoma. RESULTS: Basal cell
      adenocarcinomas are slow-growing tumours that most commonly involve the parotid
      gland and very rarely involve minor salivary glands. Although recurrence rates
      for these tumours are high, mortality rates are low. Histological diagnosis is
      important to distinguish this tumour from adenoid cystic carcinoma given the
      significant difference in disease prognosis. CONCLUSIONS: Diagnosis of these
      tumours must be made histologically. Recommended treatment options include wide
      local excision with radiotherapy reserved for close surgical margins or for local
      recurrence.

PMID- 20030820
TI  - Systematic review of epidemiological studies on health effects associated with
      management of solid waste.
AB  - BACKGROUND: Management of solid waste (mainly landfills and incineration)
      releases a number of toxic substances, most in small quantities and at extremely
      low levels. Because of the wide range of pollutants, the different pathways of
      exposure, long-term low-level exposure, and the potential for synergism among the
      pollutants, concerns remain about potential health effects but there are many
      uncertainties involved in the assessment. Our aim was to systematically review
      the available epidemiological literature on the health effects in the vicinity of
      landfills and incinerators and among workers at waste processing plants to derive
      usable excess risk estimates for health impact assessment. METHODS: We examined
      the published, peer-reviewed literature addressing health effects of waste
      management between 1983 and 2008. For each paper, we examined the study design
      and assessed potential biases in the effect estimates. We evaluated the overall
      evidence and graded the associated uncertainties. RESULTS: In most cases the
      overall evidence was inadequate to establish a relationship between a specific
      waste process and health effects; the evidence from occupational studies was not
      sufficient to make an overall assessment. For community studies, at least for
      some processes, there was limited evidence of a causal relationship and a few
      studies were selected for a quantitative evaluation. In particular, for
      populations living within two kilometres of landfills there was limited evidence
      of congenital anomalies and low birth weight with excess risk of 2 percent and 6
      percent, respectively. The excess risk tended to be higher when sites dealing
      with toxic wastes were considered. For populations living within three kilometres
      of old incinerators, there was limited evidence of an increased risk of cancer,
      with an estimated excess risk of 3.5 percent. The confidence in the evaluation
      and in the estimated excess risk tended to be higher for specific cancer forms
      such as non-Hodgkin's lymphoma and soft tissue sarcoma than for other cancers.
      CONCLUSIONS: The studies we have reviewed suffer from many limitations due to
      poor exposure assessment, ecological level of analysis, and lack of information
      on relevant confounders. With a moderate level confidence, however, we have
      derived some effect estimates that could be used for health impact assessment of
      old landfill and incineration plants. The uncertainties surrounding these numbers
      should be considered carefully when health effects are estimated. It is clear
      that future research into the health risks of waste management needs to overcome
      current limitations.

PMID- 20030821
TI  - Lipogenesis in arterial wall and vascular smooth muscular cells: regulation and
      abnormalities in insulin-resistance.
AB  - BACKGROUND: Vascular smooth muscular cells (VSMC) express lipogenic genes.
      Therefore in situ lipogenesis could provide fatty acids for triglycerides
      synthesis and cholesterol esterification and contribute to lipid accumulation in
      arterial wall with aging and during atheroma. METHODS: We investigated expression
      of lipogenic genes in human and rat arterial walls, its regulation in cultured
      VSMC and determined if it is modified during insulin-resistance and diabetes,
      situations with increased risk for atheroma. RESULTS: Zucker obese (ZO) and
      diabetic (ZDF) rats accumulated more triglycerides in their aortas than their
      respective control rats, and this triglycerides content increased with age in ZDF
      and control rats. However the expression in aortas of lipogenic genes, or of
      genes involved in fatty acids uptake, was not higher in ZDF and ZO rats and did
      not increase with age. Expression of lipogenesis-related genes was not increased
      in human arterial wall (carotid endarterectomy) of diabetic compared to non
      diabetic patients. In vitro, glucose and adipogenic medium (ADM) stimulated
      moderately the expression and activity of lipogenesis in VSMC from control rats.
      LXR agonists, but not PXR agonist, stimulated also lipogenesis in VSMC but not in
      arterial wall in vivo. Lipogenic genes expression was lower in VSMC from ZO rats
      and not stimulated by glucose or ADM. CONCLUSION: Lipogenic genes are expressed
      in arterial wall and VSMC; this expression is stimulated (VSMC) by glucose, ADM
      and LXR agonists. During insulin-resistance and diabetes, this expression is not
      increased and resists to the actions of glucose and ADM. It is unlikely that this
      metabolic pathway contribute to lipid accumulation of arterial wall during
      insulin-resistance and diabetes and thus to the increased risk of atheroma
      observed in these situations.

PMID- 20030822
TI  - Prevalence and sociodemographic correlates of stunting, underweight, and
      overweight among Palestinian school adolescents (13-15 years) in two major
      governorates in the West Bank.
AB  - BACKGROUND: There is little information about height and weight status of
      Palestinian adolescents. The objective of this paper was to assess the prevalence
      of stunting, underweight, and overweight/obesity among Palestinian school
      adolescents (13-15 years) and associated sociodemographic factors in 2 major
      governorates in the West Bank. METHODS: A Cross-sectional survey was conducted in
      2005 comprising 1942 students in 65 schools in Ramallah and Hebron governorates.
      Data was collected through self-administered questionnaires from students and
      parents. Weights and heights were measured. Overweight and obesity were assessed
      using the 2000 Centers for Disease Control and Prevention (CDC) reference and the
      International Obesity Task Force (IOTF) criteria. Stunting and underweight were
      assessed using the 2000 CDC reference. RESULTS: Overweight/obesity was more
      prevalent in Ramallah than in Hebron and affected more girls than boys. Using the
      2000 CDC reference, the prevalence of overweight and obesity in Ramallah among
      boys was 9.6% and 8.2%, respectively versus 15.6% and 6.0% among girls (P <
      0.01). In Hebron, the corresponding figures were 8.5% and 4.9% for boys and 13.5%
      and 3.4% for girls (P < 0.01). Using the IOTF criteria, the prevalence of
      overweight and obesity among boys in Ramallah was 13.3% and 5.2%, respectively
      versus 18.9% and 3.3% for girls. The prevalence of overweight and obesity among
      boys in Hebron was 10.9% and 2.2%, respectively versus 14.9% and 2.0% for girls.
      Overweight/obesity was associated with high standard of living (STL) among boys
      and with the onset of puberty among girls. More boys were underweight than girls,
      and the prevalence was higher in Hebron (12.9% and 6.0% in boys and girls,
      respectively (P < 0.01)) than in Ramallah (9.7% and 3.1% in boys and girls,
      respectively (p < 0.01)). The prevalence of stunting was similar in both
      governorates, and was higher among boys (9.2% and 9.4% in Ramallah and Hebron,
      respectively) than among girls (5.9% and 4.2% in Ramallah and Hebron,
      respectively). Stunting was negatively associated with father's education among
      boys and with urban residence, medium STL and onset of puberty among girls.
      CONCLUSION: Under- and overnutrition co-exist among Palestinian adolescents, with
      differences between sexes. Region, residence, STL, and onset of puberty were
      associated factors.

PMID- 20030823
TI  - Normal kidney size and its influencing factors - a 64-slice MDCT study of 1.040
      asymptomatic patients.
AB  - BACKGROUND: Normal ultrasound values for pole-to-pole kidney length (LPP) are
      well established for children, but very little is known about normal kidney size
      and its influencing factors in adults. The objectives of this study were thus to
      establish normal CT values for kidney dimensions from a group of unselected
      patients, identify potential influencing factors, and to estimate their
      significance. METHODS: In multiphase thin-slice MDCTs of 2.068 kidneys in 1.040
      adults, the kidney length pole to pole (LPP), parenchymal (PW) and cortical width
      (CW), position and rotation status of the kidneys, number of renal arteries,
      pyelon width and possible influencing factors that can be visualized, were
      recorded from a volume data set. For length measurements, axes were adjusted
      individually in double oblique planes using a 3D-software. Analyses of
      distribution, T-tests, ANOVA, correlation and multivariate regression analyses
      were performed. RESULTS: LPP was 108.5 +/- 12.2 mm for the right, and 111.3 +/-
      12.6 mm for the left kidney (p < 0.0001 each). PW on the right side was 15.4 +/-
      2.8 mm, slightly less than 15.9 +/- 2.7 mm on the left side (p < 0.0001), the CW
      was the same (6.6 +/- 1.9 mm). The most significant independent predictors for
      LPP, CW, and PW were body size, BMI, age, and gender (p < 0.001 each). In men,
      the LPP increases up to the fifth decade of life (p < 0.01). It is also
      influenced by the position of the kidneys, stenoses and number of renal arteries
      (SRA/NRA), infarctions suffered, parapelvic cysts, and absence of the
      contralateral kidney; CW is influenced by age, position, parapelvic cysts, NRA
      and SRA, and the PW is influenced in addition by rotation status (p < 0.05 each).
      Depending on the most important factors, gender-specific normal values were
      indicated for these dimensions, the length and width in cross section, width of
      the renal pelvis, and parenchyma-renal pyelon ratio. CONCLUSIONS: Due to the
      complex influences on kidney size, assessment should be made individually. The
      most important influencing factors are BMI, height, gender, age, position of the
      kidneys, stenoses and number of renal arteries.

PMID- 20030824
TI  - Molecular evolution of dentin phosphoprotein among toothed and toothless animals.
AB  - BACKGROUND: Dentin sialophosphoprotein (DSPP) is the largest member of the
      SIBLING family and is the most abundant noncollagenous protein in dentin. DSPP is
      also expressed in non-mineralized tissues including metabolically active ductal
      epithelia and some cancers. Its function, however, is poorly defined. The carboxy
      terminal fragment, dentin phosphoprotein (DPP) is encoded predominantly by a
      large repetitive domain that requires separate cloning/sequencing reactions and
      is, therefore, often incomplete in genomic databases. Comparison of DPP sequences
      from at least one member of each major branch in the mammalian evolutionary tree
      (including some "toothless" mammals) as well as one reptile and bird may help
      delineate its possible functions in both dentin and ductal epithelia. RESULTS:
      The BMP1-cleavage and translation-termination domains were sufficiently conserved
      to permit amplification/cloning/sequencing of most species' DPP. While the
      integrin-binding domain, RGD, was present in about half of species, only
      vestigial remnants of this tripeptide were identified in the others. The number
      of tandem repeats of the nominal SerSerAsp phosphorylation motif in toothed
      mammals (including baleen whale and platypus which lack teeth as adults), ranged
      from approximately 75 (elephant) to >230 (human). These repeats were not perfect,
      however, and patterns of intervening sequences highlight the rapidity of changes
      among even closely related species. Two toothless anteater species have evolved
      different sets of nonsense mutations shortly after their BMP1 motifs suggesting
      that while cleavage may be important for DSPP processing in other tissues, the
      DPP domain itself may be required only in dentin. The lizard DSPP had an intact
      BMP1 site, a remnant RGD motif, as well as a distinctly different Ser/Asp-rich
      domain compared to mammals. CONCLUSIONS: The DPP domain of DSPP was found to
      change dramatically within mammals and was lost in two truly toothless animals.
      The defining aspect of DPP, the long repeating phosphorylation domain, apparently
      undergoes frequent slip replication and recombination events that rapidly change
      specific patterns but not its overall biochemical character in toothed animals.
      Species may have to co-evolve protein processing mechanisms, however, to handle
      increased lengths of DSP repeats. While the RGD domain is lost in many species,
      some evolutionary pressure to maintain integrin binding can be observed.

PMID- 20030825
TI  - Immunologic aspects of patients with disseminated bacille Calmette-Guerin disease
      in north-west of Iran.
AB  - BACKGROUND: Adverse reactions induced by BCG vaccination are rare, disseminated
      mycobacterial BCG infection in particular, which is often fatal and results from
      impaired immunity. The aim of this study is to determine the nature of the
      immunodeficiences in patients with disseminated BCG infection in northwest region
      of Iran. MATERIALS AND METHODS: Through 2 years all infants with BCG adenitis or
      other complications of this vaccine that had suspicious BCG infection were
      referred to children's hospital and health centers of Tabriz. Evaluation of
      immune system and in some cases genetic survey was performed in infants with
      evidence of histopathologic demonstration of acid-fast bacilli. Then frequency of
      infants who had disseminated BCG infection with immunodeficiency was defined.
      RESULTS: From 48 selected infants with complications of BCG vaccine in the range
      of 2 to 62 months, 28 infants (58.3%) were male and 20 infants (41.7%) were
      female. Disseminated BCG infection was diagnosed in 11 cases, almost all of whom
      had immunodeficiency as follows: Seven cases had severe combined immunodeficiency
      and one cases had chronic granulomatous disease. MSMD in two cases and IL12 R
      deficiency in another one was diagnosed. Overall, the mortality rate was 72.8% (8
      cases) which 7 cases of them were SCID and another one CGD Consanguineous was
      found in more than half (7 cases) of patients and family history of disseminated
      BCG infection or immunodeficiency was found in nearly one third (3 cases) of
      patients. DISCUSSION: BCG vaccine is administered world wide to prevent
      tuberculosis and is considered to have excellent safety profile. However in some
      immunodeficient patients it can cause severe and fatal complications, like in our
      region, where all cases of disseminated BCG infection with severe
      immunodeficiency died. CONCLUSION: BCG vaccination is necessary in some countries
      such as Iran, so it seems that development of a more safer vaccine and change of
      vaccine program in the families with history of inherited immunodeficiency can be
      identifies such high risk infants and prophylaxis of severe complications or dead
      in such patients.

PMID- 20030826
TI  - The requirements and challenges in preventing of road traffic injury in Iran. A
      qualitative study.
AB  - BACKGROUND: Road traffic injuries (RTIs) are a major public health problem,
      especially in low- and middle-income countries. Among middle-income countries,
      Iran has one of the highest mortality rates from RTIs. Action is critical to
      combat this major public health problem. Stakeholders involved in RTI control are
      of key importance and their perceptions of barriers and facilitators are a vital
      source of knowledge. The aim of this study was to explore barriers to the
      prevention of RTIs and provide appropriate suggestions for prevention, based on
      the perceptions of stakeholders, victims and road-users as regards RTIs. METHODS:
      Thirty-eight semi-structured interviews were conducted with informants in the
      field of RTI prevention including: police officers; public health professionals;
      experts from the road administrators; representatives from the General Governor,
      the car industry, firefighters; experts from Emergency Medical Service and the
      Red Crescent; and some motorcyclists and car drivers as well as victims of RTIs.
      A qualitative approach using grounded theory method was employed to analyze the
      material gathered. RESULTS: The core variable was identified as "The lack of a
      system approach to road-user safety". The following barriers in relation to RTI
      prevention were identified as: human factors; transportation system; and
      organizational coordination. Suggestions for improvement included education (for
      the general public and targeted group training), more effective legislation, more
      rigorous law enforcement, improved engineering in road infrastructure, and an
      integrated organization to supervise and coordinate preventive activities.
      CONCLUSION: The major barriers identified in this study were human factors and
      efforts to change human behaviour were suggested by means of public education
      campaigns and stricter law enforcement. However, the lack of a system approach to
      RTI prevention was also an important concern. There is an urgent need for both an
      integrated system to coordinate RTI activities and prevention and a major change
      in stakeholders' attitudes towards RTI prevention. The focus of all activities
      should take place on road users' safety.

PMID- 20030827
TI  - Are there geographic and socio-economic differences in incidence, burden and
      prevention of malaria? A study in southeast Nigeria.
AB  - RATIONALE: It is not clearly evident whether malaria affects the poor more
      although it has been argued that the poor bear a very high burden of the disease.
      This study explored the socioeconomic and geographic differences in incidence and
      burden of malaria as well as ownership of mosquito nets. METHODS: Structured
      questionnaires were used to collect information from 1657 respondents from rural
      and urban communities in southeast Nigeria on: incidence of malaria, number of
      days lost to malaria; actions to treat malaria and household ownership of
      insecticide treated and untreated mosquito nets. Data was compared across socio
      economic status (SES) quartiles and between urban and rural dwellers. RESULTS:
      There was statistically significant urban-rural difference in malaria occurrence
      with malaria occurring more amongst urban dwellers. There was more reported
      occurrence of malaria amongst children and other adult household members in
      better-off SES groups compared to worse-off SES groups, but not amongst
      respondents. The average number of days that people delayed before seeking
      treatment was two days, and both adults and children were ill with malaria for
      about six days. Better-off SES quartile and urban dwellers owned more mosquito
      nets (p < 0.05) (treated and untreated). CONCLUSION: Malaria occurs more amongst
      better-off SES groups and urban dwellers in southeast Nigeria. Deployment of
      malaria control interventions should ensure universal access since targeting the
      poor and other supposedly vulnerable groups may exclude people that really
      require malaria control services.

PMID- 20030828
TI  - A rhodanine agent active against non-replicating intracellular Mycobacterium
      avium subspecies paratuberculosis.
AB  - BACKGROUND: Antibiotic therapy targeting chronic mycobacterial disease is often
      ineffective due to problems with the emergence of drug resistance and non
      replicating persistent intracellular antibiotic resistant phenotypes. Strategies
      which include agents able to enhance host cell killing mechanisms could represent
      an alternative to conventional methods with the potential for host clearance if
      active against dormant phenotypes. Investigations of agents with potential
      activity against non-replicating mycobacteria however are restricted due to a
      need for assays that can assess bacterial viability without having to culture.
      RESULTS: This study describes the development and use of a pre16S ribosomal gene
      RNA/DNA ratio viability assay which is independent of the need for culture,
      supported by a novel thin layer accelerated mycobacterial colony forming method
      for determining viability and culturability of MAP in intracellular environments.
      We describe the use of these tools to demonstrate intracellular killing activity
      of a novel rhodanine agent (D157070) against the intracellular pathogen
      Mycobacterium avium subspecies paratuberculosis (MAP) and show that the
      culturability of MAP decreases relative to its viability on intracellular entry
      suggesting the induction of a non-culturable phenotype. We further demonstrate
      that D157070, although having no direct activity against the culturability of
      extracellular MAP, can bind to cultured MAP cells and has significant influence
      on the MAP transcriptome, particularly with respect of delta(L )associated genes.
      D157070 is shown to be taken up by bovine and human cells and able to enhance
      host cell killing, as measured by significant decreases in both culturability and
      viability of intracellular MAP. CONCLUSIONS: This work suggests that pre16srRNA
      gene ratios represent a viable method for studying MAP viability. In addition,
      the rhodanine agent D157070 tested is non-toxic and enhances cell killing
      activity against both growing and latent MAP phenotypes.

PMID- 20030829
TI  - Neural progenitor cells attenuate inflammatory reactivity and neuronal loss in an
      animal model of inflamed AD brain.
AB  - BACKGROUND: Transplantation of neural progenitor cells (NPC) constitutes a
      putative therapeutic maneuver for use in treatment of neurodegenerative diseases.
      At present, effects of NPC transplantation in Alzheimer's disease (AD) brain are
      largely unknown and a primary objective of this work was to demonstrate possible
      efficacy of NPC administration in an animal model of AD. The benefits of
      transplantation could involve a spectrum of effects including replacement of
      endogenous neurons or by conferring neuroprotection with enhancement of
      neurotrophic factors or diminishing levels of neurotoxic agents. Since chronic
      inflammation is a characteristic property of AD brain, we considered that
      transplantation of NPC could have particular utility in inhibiting ongoing
      inflammatory reactivity. We have tested intrahippocampal transplantation of NPC
      for efficacy in attenuating inflammatory responses and for neuroprotection in
      beta-amyloid (Abeta1-42) peptide-injected rat hippocampus. METHODS: Spheres of
      neural progenitor cells were grown from dissociated telencephalon tissue of rat
      embryos. NPC were infected with lentiviral vector green fluorescent protein (GFP)
      with subsequent cell transplantation into rat hippocampus previously injected (3
      d prior) with Abeta1-42 peptide or PBS control. Immunohistochemical analysis was
      carried out (7 d post-NPC transplantation, 10 d post-peptide/PBS injection) for
      GFP, microgliosis (Iba-1 marker), astrogliosis (GFAP marker), neuron viability
      (MAP-2 marker) and levels of the proinflammatory cytokine, TNF-alpha. RESULTS:
      Successful infection of cultured NPC with lentiviral vector green fluorescent
      protein (GFP) was demonstrated prior to cell transplantation into rat
      hippocampus. In vivo, immunohistochemical staining showed migration of GFP
      positive cells, in a region of dentate gyrus between Abeta1-42/PBS injection site
      and NPC transplantation site, was increased x2.8-fold with Abeta1-42 compared to
      PBS injection. Double immunostaining in peptide-injected brain indicated GFP
      association with nestin and GFAP, but not MAP-2. Cell-specific immunostaining
      showed marked increases in microgliosis and astrogliosis in Abeta1-42-injected
      brain (respective increases of x4.3- and x4.6-fold compared with PBS injection).
      NPC transplantation significantly reduced microgliosis (by 38%) but not
      astrogliosis in peptide-injected hippocampus. The proinflammatory cytokine TNF
      alpha was elevated by 6.7-fold (peptide vs PBS injection) with NPC administration
      attenuating levels of TNF-alpha (by 40%). Peptide-injected brain demonstrated
      neuronal loss (MAP-2 staining reduced by 45% vs PBS injection) with NPC
      transplantation effective in conferring neuroprotection (26% recovery of
      neurons). CONCLUSIONS: These findings indicate efficacy for NPC transplantation
      in an animal model of AD with effects consistent with cellular actions to
      attenuate inflammatory reactivity induced by intrahippocampal peptide injection.

PMID- 20030830
TI  - Screening asymptomatic patients with diabetes for unknown coronary artery
      disease: does it reduce risk? An open-label randomized trial comparing a strategy
      based on exercise testing aimed at revascularization with management based on
      pharmacological/behavioural treatment of traditional risk factors. DADDY-D Trial
      (Does coronary Atherosclerosis Deserve to be Diagnosed and treated early in
      Diabetics?).
AB  - BACKGROUND: Coronary artery disease is the leading cause of morbidity and
      mortality in patients with type 2 diabetes. Screening for asymptomatic coronary
      artery disease with treatment by means of revascularization seems to be an
      appealing option for prevention. The utility of such a strategy has never been
      challenged in a randomized trial. METHODS/DESIGN: In the present study a cohort
      of diabetic patients without any symptoms and without known coronary artery
      disease will be screened at two diabetes outpatients services. Those with
      intermediate or high risk (equal or greater than 10% according to the Italian
      risk chart) will be asked to participate and enrolled. They will be seen and
      followed in order to provide the best adherence to medical therapy. Half of the
      patients will be randomized to undergo an exercise tolerance testing while the
      other group will continue to be regularly seen at diabetes outpatients services.
      Best medical/behavioral therapy will be offered to both groups. Those patients
      with a positive exercise tolerance testing will be studied by coronary
      angiography and treated according to the severity of coronary lesions by
      percutaneous stenting or surgery.The objective of the study is to evaluate the
      efficacy of the screening strategy aimed at revascularization. A cost
      effectiveness analysis will be performed at the end of the follow up. DISCUSSION:
      The study will provide useful information about prevention and treatment of
      diabetic patients at high risk of coronary events. It will be made clearer if
      detection of silent coronary artery disease has to be recommended and followed by
      treatment. Given the simplicity of the study protocol, it will be easily
      transferable to the real world. TRIAL REGISTRATION: (ClinicalTrials.gov):
      NCT00547872.

PMID- 20030831
TI  - SP-D counteracts GM-CSF-mediated increase of granuloma formation by alveolar
      macrophages in lysinuric protein intolerance.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a syndrome with multiple
      etiologies and is often deadly in lysinuric protein intolerance (LPI). At
      present, PAP is treated by whole lung lavage or with granulocyte/monocyte colony
      stimulating factor (GM-CSF); however, the effectiveness of GM-CSF in treating LPI
      associated PAP is uncertain. We hypothesized that GM-CSF and surfactant protein D
      (SP-D) would enhance the clearance of proteins and dying cells that are typically
      present in the airways of PAP lungs. METHODS: Cells and cell-free supernatant of
      therapeutic bronchoalveolar lavage fluid (BALF) of a two-year-old patient with
      LPI were isolated on multiple occasions. Diagnostic BALF samples from an age
      matched patient with bronchitis or adult PAP patients were used as controls. SP-D
      and total protein content of the supernatants were determined by BCA assays and
      Western blots, respectively. Cholesterol content was determined by a calorimetic
      assay or Oil Red O staining of cytospin preparations. The cells and surfactant
      lipids were also analyzed by transmission electron microscopy. Uptake of Alexa
      647 conjugated BSA and DiI-labelled apoptotic Jurkat T-cells by BAL cells were
      studied separately in the presence or absence of SP-D (1 microg/ml) and/or GM-CSF
      (10 ng/ml), ex vivo. Specimens were analyzed by light and fluorescence
      microscopy. RESULTS: Here we show that large amounts of cholesterol, and large
      numbers of cholesterol crystals, dying cells, and lipid-laden foamy alveolar
      macrophages were present in the airways of the LPI patient. Although SP-D is
      present, its bioavailability is low in the airways. SP-D was partially degraded
      and entrapped in the unusual surfactant lipid tubules with circular lattice, in
      vivo. We also show that supplementing SP-D and GM-CSF increases the uptake of
      protein and dying cells by healthy LPI alveolar macrophages, ex vivo.
      Serendipitously, we found that these cells spontaneously generated granulomas, ex
      vivo, and GM-CSF treatment drastically increased the number of granulomas whereas
      SP-D treatment counteracted the adverse effect of GM-CSF. CONCLUSIONS: We propose
      that increased GM-CSF and decreased bioavailability of SP-D may promote granuloma
      formation in LPI, and GM-CSF may not be suitable for treating PAP in LPI. To
      improve the lung condition of LPI patients with PAP, it would be useful to
      explore alternative therapies for increasing dead cell clearance while decreasing
      cholesterol content in the airways.

PMID- 20030833
TI  - Single strand conformation polymorphism based SNP and Indel markers for genetic
      mapping and synteny analysis of common bean (Phaseolus vulgaris L.).
AB  - BACKGROUND: Expressed sequence tags (ESTs) are an important source of gene-based
      markers such as those based on insertion-deletions (Indels) or single-nucleotide
      polymorphisms (SNPs). Several gel based methods have been reported for the
      detection of sequence variants, however they have not been widely exploited in
      common bean, an important legume crop of the developing world. The objectives of
      this project were to develop and map EST based markers using analysis of single
      strand conformation polymorphisms (SSCPs), to create a transcript map for common
      bean and to compare synteny of the common bean map with sequenced chromosomes of
      other legumes. RESULTS: A set of 418 EST based amplicons were evaluated for
      parental polymorphisms using the SSCP technique and 26% of these presented a
      clear conformational or size polymorphism between Andean and Mesoamerican
      genotypes. The amplicon based markers were then used for genetic mapping with
      segregation analysis performed in the DOR364 x G19833 recombinant inbred line
      (RIL) population. A total of 118 new marker loci were placed into an integrated
      molecular map for common bean consisting of 288 markers. Of these, 218 were used
      for synteny analysis and 186 presented homology with segments of the soybean
      genome with an e-value lower than 7 x 10-12. The synteny analysis with soybean
      showed a mosaic pattern of syntenic blocks with most segments of any one common
      bean linkage group associated with two soybean chromosomes. The analysis with
      Medicago truncatula and Lotus japonicus presented fewer syntenic regions
      consistent with the more distant phylogenetic relationship between the galegoid
      and phaseoloid legumes. CONCLUSION: The SSCP technique is a useful and
      inexpensive alternative to other SNP or Indel detection techniques for saturating
      the common bean genetic map with functional markers that may be useful in marker
      assisted selection. In addition, the genetic markers based on ESTs allowed the
      construction of a transcript map and given their high conservation between
      species allowed synteny comparisons to be made to sequenced genomes. This synteny
      analysis may support positional cloning of target genes in common bean through
      the use of genomic information from these other legumes.

PMID- 20030834
TI  - Infection of the malaria mosquito, Anopheles gambiae, with two species of
      entomopathogenic fungi: effects of concentration, co-formulation, exposure time
      and persistence.
AB  - BACKGROUND: Entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana
      isolates have been shown to infect and reduce the survival of mosquito vectors.
      METHODS: Here four different bioassays were conducted to study the effect of
      conidia concentration, co-formulation, exposure time and persistence of the
      isolates M. anisopliae ICIPE-30 and B. bassiana I93-925 on infection and survival
      rates of female Anopheles gambiae sensu stricto. Test concentrations and exposure
      times ranged between 1 x 10(7) - 4 x 10(10) conidia m(-2) and 15 min - 6 h. In co
      formulations, 2 x 10(10) conidia m(-2) of both fungus isolates were mixed at
      ratios of 4:1, 2:1, 1:1,1:0, 0:1, 1:2 and 1:4. To determine persistence,
      mosquitoes were exposed to surfaces treated 1, 14 or 28 d previously, with
      conidia concentrations of 2 x 10(9), 2 x 10(10) or 4 x 10(10). RESULTS: Mosquito
      survival varied with conidia concentration; 2 x 10(10) conidia m(-2) was the
      concentration above which no further reductions in survival were detectable for
      both isolates of fungus. The survival of mosquitoes exposed to single and co
      formulated treatments was similar and no synergistic or additive effects were
      observed. Mosquitoes were infected within 30 min and longer exposure times did
      not result in a more rapid killing effect. Fifteen min exposure still achieved
      considerable mortality rates (100% mortality by 14 d) of mosquitoes, but at lower
      speed than with 30 min exposure (100% mortality by 9 d). Conidia remained
      infective up to 28 d post-application but higher concentrations did not increase
      persistence. CONCLUSION: Both fungus isolates are effective and persistent at low
      concentrations and short exposure times.

PMID- 20030832
TI  - Quality of life data as prognostic indicators of survival in cancer patients: an
      overview of the literature from 1982 to 2008.
AB  - BACKGROUND: Health-related quality of life and survival are two important outcome
      measures in cancer research and practice. The aim of this paper is to examine the
      relationship between quality of life data and survival time in cancer patients.
      METHODS: A review was undertaken of all the full publications in the English
      language biomedical journals between 1982 and 2008. The search was limited to
      cancer, and included the combination of keywords 'quality of life', 'patient
      reported-outcomes' 'prognostic', 'predictor', 'predictive' and 'survival' that
      appeared in the titles of the publications. In addition, each study was examined
      to ensure that it used multivariate analysis. Purely psychological studies were
      excluded. A manual search was also performed to include additional papers of
      potential interest. RESULTS: A total of 451 citations were identified in this
      rapid and systematic review of the literature. Of these, 104 citations on the
      relationship between quality of life and survival were found to be relevant and
      were further examined. The findings are summarized under different headings:
      heterogeneous samples of cancer patients, lung cancer, breast cancer, gastro
      oesophageal cancers, colorectal cancer, head and neck cancer, melanoma and other
      cancers. With few exceptions, the findings showed that quality of life data or
      some aspects of quality of life measures were significant independent predictors
      of survival duration. Global quality of life, functioning domains and symptom
      scores - such as appetite loss, fatigue and pain - were the most important
      indicators, individually or in combination, for predicting survival times in
      cancer patients after adjusting for one or more demographic and known clinical
      prognostic factors. CONCLUSION: This review provides evidence for a positive
      relationship between quality of life data or some quality of life measures and
      the survival duration of cancer patients. Pre-treatment (baseline) quality of
      life data appeared to provide the most reliable information for helping
      clinicians to establish prognostic criteria for treating their cancer patients.
      It is recommended that future studies should use valid instruments, apply sound
      methodological approaches and adequate multivariate statistical analyses adjusted
      for socio-demographic characteristics and known clinical prognostic factors with
      a satisfactory validation strategy. This strategy is likely to yield more
      accurate and specific quality of life-related prognostic variables for specific
      cancers.

PMID- 20030835
TI  - Effect on health-related quality of life of changes in mental health in children
      and adolescents.
AB  - BACKGROUND: The objective of the study was to assess the effect of changes in
      mental health status on health-related quality of life (HRQOL) in children and
      adolescents aged 8 - 18 years. METHODS: A representative sample of Spanish
      children and adolescents aged 8-18 years completed the self-administered
      KIDSCREEN-52 questionnaire at baseline and after 3 years. Mental health status
      was measured using the Strengths and Difficulties Questionnaire (SDQ). Changes on
      SDQ scores over time were used to classify respondents in one of 3 categories
      (improved, stable, worsened). Data was also collected on gender, undesirable life
      events, and family socio-economic status. Changes in HRQOL were evaluated using
      effect sizes (ES). A multivariate analysis was performed to identify predictors
      of poor HRQOL at follow-up. RESULTS: Response rate at follow-up was 54% (n =
      454). HRQOL deteriorated in all groups on most KIDSCREEN dimensions. Respondents
      who worsened on the SDQ showed the greatest deterioration, particularly on
      Psychological well-being (ES = -0.81). Factors most strongly associated with a
      decrease in HRQOL scores were undesirable life events and worsening SDQ score.
      CONCLUSIONS: Changes in mental health status affect children and adolescents'
      HRQOL. Improvements in mental health status protect against poorer HRQOL while a
      worsening in mental health status is a risk factor for poorer HRQOL.

PMID- 20030836
TI  - Identification of mammalian orthologs using local synteny.
AB  - BACKGROUND: Accurate determination of orthology is central to comparative
      genomics. For vertebrates in particular, very large gene families, high rates of
      gene duplication and loss, multiple mechanisms of gene duplication, and high
      rates of retrotransposition all combine to make inference of orthology between
      genes difficult. Many methods have been developed to identify orthologous genes,
      mostly based upon analysis of the inferred protein sequence of the genes. More
      recently, methods have been proposed that use genomic context in addition to
      protein sequence to improve orthology assignment in vertebrates. Such methods
      have been most successfully implemented in fungal genomes and have long been used
      in prokaryotic genomes, where gene order is far less variable than in
      vertebrates. However, to our knowledge, no explicit comparison of synteny and
      sequence based definitions of orthology has been reported in vertebrates, or,
      more specifically, in mammals. RESULTS: We test a simple method for the
      measurement and utilization of gene order (local synteny) in the identification
      of mammalian orthologs by investigating the agreement between coding sequence
      based orthology (Inparanoid) and local synteny based orthology. In the 5
      mammalian genomes studied, 93% of the sampled inter-species pairs were found to
      be concordant between the two orthology methods, illustrating that local synteny
      is a robust substitute to coding sequence for identifying orthologs. However, 7%
      of pairs were found to be discordant between local synteny and Inparanoid. These
      cases of discordance result from evolutionary events including retrotransposition
      and genome rearrangements. CONCLUSIONS: By analyzing cases of discordance between
      local synteny and Inparanoid we show that local synteny can distinguish between
      true orthologs and recent retrogenes, can resolve ambiguous many-to-many
      orthology relationships into one-to-one ortholog pairs, and might be used to
      identify cases of non-orthologous gene displacement by retroduplicated paralogs.

PMID- 20030837
TI  - A case of polymicrogyria in macaque monkey: impact on anatomy and function of the
      motor system.
AB  - BACKGROUND: Polymicrogyria is a malformation of the cerebral cortex often
      resulting in epilepsy or mental retardation. It remains unclear whether this
      pathology affects the structure and function of the corticospinal (CS) system.
      The anatomy and histology of the brain of one macaque monkey exhibiting a
      spontaneous polymicrogyria (PMG monkey) were examined and compared to the brain
      of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA)
      unilaterally in a region where low intensity electrical microstimulation elicited
      contralateral hand movements (presumably the primary motor cortex in the PMG
      monkey). RESULTS: The examination of the brain showed a large number of microgyri
      at macro- and microscopic levels, covering mainly the frontoparietal regions. The
      layered cortical organization was locally disrupted and the number of SMI-32
      stained pyramidal neurons in the cortical layer III of the presumed motor cortex
      was reduced. We compared the distribution of labelled CS axons in the PMG monkey
      at spinal cervical level C5. The cumulated length of CS axon arbors in the spinal
      grey matter was not significantly different in the PMG monkey. In the red
      nucleus, numerous neurons presented large vesicles. We also assessed its motor
      performances by comparing its capacity to execute a complex reach and grasp
      behavioral task. The PMG monkey exhibited an increase of reaction time without
      any modification of other motor parameters, an observation in line with a normal
      CS tract organisation. CONCLUSION: In spite of substantial cortical malformations
      in the frontal and parietal lobes, the PMG monkey exhibits surprisingly normal
      structure and function of the corticospinal system.

PMID- 20030838
TI  - Neural networks for modeling gene-gene interactions in association studies.
AB  - BACKGROUND: Our aim is to investigate the ability of neural networks to model
      different two-locus disease models. We conduct a simulation study to compare
      neural networks with two standard methods, namely logistic regression models and
      multifactor dimensionality reduction. One hundred data sets are generated for
      each of six two-locus disease models, which are considered in a low and in a high
      risk scenario. Two models represent independence, one is a multiplicative model,
      and three models are epistatic. For each data set, six neural networks (with up
      to five hidden neurons) and five logistic regression models (the null model,
      three main effect models, and the full model) with two different codings for the
      genotype information are fitted. Additionally, the multifactor dimensionality
      reduction approach is applied. RESULTS: The results show that neural networks are
      more successful in modeling the structure of the underlying disease model than
      logistic regression models in most of the investigated situations. In our
      simulation study, neither logistic regression nor multifactor dimensionality
      reduction are able to correctly identify biological interaction. CONCLUSIONS:
      Neural networks are a promising tool to handle complex data situations. However,
      further research is necessary concerning the interpretation of their parameters.

PMID- 20030839
TI  - The repertoire of equine intestinal alpha-defensins.
AB  - BACKGROUND: Defensins represent an important class of antimicrobial peptides.
      These effector molecules of the innate immune system act as endogenous
      antibiotics to protect the organism against infections with pathogenic
      microorganisms. Mammalian defensins are classified into three distinct sub
      families (alpha-, beta- and theta-defensins) according to their specific
      intramolecular disulfide-bond pattern. The peptides exhibit an antimicrobial
      activity against a broad spectrum of microorganisms including bacteria and fungi.
      Alpha-Defensins are primarily synthesised in neutrophils and intestinal Paneth
      cells. They play a role in the pathogenesis of intestinal diseases and may
      regulate the flora of the intestinal tract. An equine intestinal alpha-defensin
      (DEFA1), the first characterised in the Laurasiatheria, shows a broad
      antimicrobial spectrum against human and equine pathogens. Here we report a first
      investigation of the repertoire of equine intestinal alpha-defensins. The equine
      genome was screened for putative alpha-defensin genes by using known alpha
      defensin sequences as matrices. Based on the obtained sequence information, a set
      of oligonucleotides specific to the alpha-defensin gene-family was designed. The
      products generated by reverse-transcriptase PCR with cDNA from the small
      intestine as template were sub-cloned and numerous clones were sequenced.
      RESULTS: Thirty-eight equine intestinal alpha-defensin transcripts were
      determined. After translation it became evident that at least 20 of them may code
      for functional peptides. Ten transcripts lacked matching genomic sequences and
      for 14 alpha-defensin genes apparently present in the genome no appropriate
      transcript could be verified. In other cases the same genomic exons were found in
      different transcripts. CONCLUSIONS: The large repertoire of equine alpha
      defensins found in this study points to a particular importance of these peptides
      regarding animal health and protection from infectious diseases. Moreover, these
      findings make the horse an excellent species to study biological properties of
      alpha-defensins. Interestingly, the peptides were not found in other species of
      the Laurasiatheria to date. Comparison of the obtained transcripts with the
      genomic sequences in the current assembly of the horse (EquCab2.0) indicates that
      it is yet not complete and/or to some extent falsely assembled.

PMID- 20030840
TI  - Sphingobacterium respiratory tract infection in patients with cystic fibrosis.
AB  - BACKGROUND: Bacteria that belong to the genus Sphingobacterium are Gram-negative,
      non-fermentative bacilli, ubiquitous in nature and rarely involved in human
      infections. The aims of this study were to evaluate the epidemiology of infection
      by Sphingobacterium in a cohort of patients affected by Cystic Fibrosis (CF), the
      antibiotic susceptibility and the DNA fingerprinting of the isolated strains and
      to analyze some clinical outcomes of the infected patients. FINDINGS: Between
      January 2006 and June 2008, patients (n = 332) attending the Regional CF Unit in
      Naples, Italy, were enrolled. Sputum samples were processed for microscopic,
      cultural, phenotypic identification and antibiotic susceptibility testing. DNA
      fingerprinting was performed by pulsed-field gel electrophoresis (PFGE). A total
      of 21 strains of Sphingobacterium were isolated from 7 patients (13 of S.
      spiritovorum, 8 of S. multivorum). S. multivorum isolates were more resistant
      than those of S. spiritovorum. PFGE profiles were in general heterogeneous, which
      suggested independent circulation. CONCLUSIONS: This is the first Italian report
      about respiratory tract infections by Sphingobacterium in CF patients. In our
      cohort, these infections were not associated with a deterioration of pulmonary
      function during the follow-up period. Although the exact role of this
      microorganism in CF lung disease is unknown and the number of infected patients
      was small, this study could represent an important starting-point for
      understanding the epidemiology and the possible pathogenic role of
      Sphingobacterium in CF patients.

PMID- 20030841
TI  - Treatment outcomes and plasma level of ritonavir-boosted lopinavir monotherapy
      among HIV-infected patients who had NRTI and NNRTI failure.
AB  - BACKGROUND: Different strategies of ritonavir-boosted lopinavir monotherapy have
      been explored; however, data regarding salvage therapy among HIV-infected
      patients who failed nucleoside reverse transcriptase inhibitor (NRTI) and non
      nucleoside reverse transcriptase inhibitor (NNRTI) is still limited. METHODS: A
      prospective study was conducted among HIV-infected patients who failed NNRTI
      based antiretroviral therapy with M184V, TAMs, and NNRTI mutations, and were
      naive to protease inhibitor. LPV/r at 400/100 mg and lamivudine 150 mg were given
      twice daily. CD4 and HIV-1 RNA were monitored at week 0, 12, 24, and 48. LPV Cmin
      was assayed for the first 14 patients using HPLC. RESULTS: There were 40 patients
      with a mean age of 37 years and 70% were male. Median (IQR) baseline CD4 was 123
      (37-245) cells/mm(3) and median (IQR) HIV-1 RNA was 55,800 (9,670-100,000)
      copies/mL. By intend-to-treat analysis, 30 (75%) and 24 (60%) patients achieved
      HIV-1 RNA at <400 and <50 copies/mL, respectively. In as-treated analysis, the
      corresponding rates were 29 (83%) and 23 (67%), respectively. Low-level viral
      rebound was found in 6 (15%) patients at week 48. Medians CD4 at week 12, 24, 36
      and 48 were 249, 283, 307, and 351 cells/mm(3) and significantly changed from
      baseline (all, P < 0.05). At 6 and 12 weeks, median (min-max) LPV Cmin was 6.52
      (1.62-11.64) mg/L and 5.79 (0.75-16.31) mg/L, respectively. There were increments
      of mean total cholesterol and triglyceride at 48 weeks from baseline (P < 0.05).
      CONCLUSION: LPV/r monotherapy with recycled lamivudine can maintain virological
      suppression in a substantial proportion of patients failing NNRTI-based regimen
      and provides adequate plasma concentrations of LPV although the incidence of low
      level viremia is relatively high.

PMID- 20030842
TI  - Students' and teachers' perceptions of clinical assessment program: A qualitative
      study in a PBL curriculum.
AB  - BACKGROUND: "Examinations drive students' learning." This statement refers to
      what is assumed to be one of the strongest relationships in education. We
      explored in this research how and why students differ in their approaches to
      learning, how assessment affects deep learning, and which barriers stand in the
      way of good assessment and learning in the clinical years of a Problem Based
      Learning (PBL) graduate entry medical curriculum. FINDINGS:  METHOD: We conducted
      a qualitative, phenomenological study using semi-structured group interviews with
      students and semi-structured individual interviews with teachers and students.
      The transcripts were analyzed, and themes were identified. SETTING: The research
      was conducted at the King Saud bin Abdulaziz University for Health Sciences,
      College of Medicine, Riyadh, Saudi Arabia from November 2007 to March 2008.
      RESULTS: A total of 28 students participated in 7 focus group interviews. Semi
      structured individual interviews were conducted with 12 teachers and 12 students.
      The analysis yielded four themes: summative assessment, formative assessment,
      continuous assessment of clinical attachments, and learning objectives.
      CONCLUSIONS: The results of this study confirm that assessment affects students'
      perceptions of learning and how they learn. These effects are not uniformly
      positive. According to the students, the predominantly summative assessment
      program offers little inducement to engage in deep learning. They express a clear
      preference for formative assessment, which may foster a deeper approach to
      learning. Efforts to achieve more clinically relevant assessment with adequate
      balance between the various types of assessment are required. Research is needed
      to decide this balance.

PMID- 20030843
TI  - Rationale and design of WEBCARE: a randomized, controlled, web-based behavioral
      intervention trial in cardioverter-defibrillator patients to reduce anxiety and
      device concerns and enhance quality of life.
AB  - BACKGROUND: The implantable cardioverter defibrillator (ICD) is generally well
      accepted, but 25-33% of patients experience clinical levels of anxiety,
      depression, and impaired quality of life (QoL) following implantation. Few trials
      in ICD patients have investigated whether behavioral intervention may mitigate
      the development of these adjustment problems. We present the rationale and study
      design of the WEB-based distress management program for implantable CARdioverter
      dEfibrillator patients (WEBCARE) trial. METHODS: WEBCARE is a multi-center, multi
      disciplinary, randomized, controlled behavioral intervention trial designed to
      examine the effectiveness of a web-based approach in terms of reducing levels of
      anxiety and device concerns and enhancing QoL. Consecutive patients hospitalized
      for the implantation of an ICD will be approached for study participation while
      in hospital and randomized to the intervention arm (n = 175) versus usual care (n
      = 175) at baseline (5-10 days post implantation). Patients will complete
      assessments of patient-centered outcomes at baseline, 14, 26, and 52 weeks after
      implantation. Patients randomized to the intervention arm will receive a 12-week
      web-based behavioral intervention starting 2 weeks after implantation. Primary
      endpoints include (i(i)) patient-centered outcomes (i.e., anxiety, depression,
      ICD acceptance, QoL); (i(ii)) health care utilization; and (i(iii)) cost
      effectiveness. All primary endpoints will be assessed with standardized and
      validated disease-specific or generic questionnaires. Secondary endpoints include
      (ii(i)) cortisol awakening response; and (ii(ii)) ventricular arrhythmias.
      DISCUSSION: WEBCARE will show whether a behavioral intervention using a web-based
      approach is feasible and effective in reducing anxiety and ICD concerns and
      improving QoL in ICD patients. TRIAL REGISTRATION: http://www.ClinicalTrials.gov.
      Identifier: NCT00895700.

PMID- 20030844
TI  - ERG is required for the differentiation of embryonic stem cells along the
      endothelial lineage.
AB  - BACKGROUND: The molecular mechanisms that govern stem cell differentiation along
      the endothelial lineage remain largely unknown. Ets related gene (ERG) has
      recently been shown to participate in the transcriptional regulation of a number
      of endothelial specific genes including VE-cadherin (CD144), endoglin, and von
      Willebrand's Factor (vWF). The specific role of the ETS factor ERG during
      endothelial differentiation has not been evaluated. RESULTS: ERG expression and
      function were evaluated during the differentiation of embryonic stem cells into
      embryoid bodies (EB). The results of our study demonstrate that ERG is first
      expressed in a subpopulation of vascular endothelial growth factor receptor 2
      (VEGF-R2) expressing cells that also express VE-cadherin. During ES cell
      differentiation, ERG expression remains restricted to cells of the endothelial
      lineage that eventually coalesce into primitive vascular structures within
      embryoid bodies. ERG also exhibits an endothelial cell (EC)-restricted pattern
      during embryogenesis. To further define the role of ERG during ES cell
      differentiation, we used a knockdown strategy to inhibit ERG expression. Delivery
      of three independent shRNA led to 70-85% reductions in ERG expression during ES
      cell differentiation compared to no change with control shRNA. ERG knockdown was
      associated with a marked reduction in the number of ECs, the expression of EC
      restricted genes, and the formation of vascular structures. CONCLUSION: The ETS
      factor ERG appears to be a critical regulator of EC differentiation.

PMID- 20030846
TI  - Temporal analysis of the incidence of meningitis in the Tehran metropolitan area,
      1999-2005.
AB  - OBJECTIVES: The aim of this study was to describe the temporal determinants of
      meningitis incidence in the population living in the Tehran metropolis. METHODS:
      All cases of meningitis reported to health districts throughout the Tehran
      metropolis from 1999 to 2005 were abstracted from patient files. Referral cases
      (patients who did not reside in the Tehran metropolis) were excluded. For each
      year, sex- and age-specific incidences were estimated. Temporality and its
      determinants were analyzed using Poisson regression. RESULTS: Age-specific
      incidence is highest among males younger than 5 years of age at 10.2 cases per
      100,000 population per year. The lowest incidence was among females aged 30 to 40
      years at 0.72 cases per 100,000 population per year, with an overall male-to
      female incidence ratio of 2.1. The temporal analysis showed seasonality, with a
      higher risk of meningitis in spring at a rate ratio of 1.31 with a 95% confidence
      interval (CI) of 1.20 to 1.41 and in autumn (rate ratio = 1.16, 95% CI 1.06,
      1.27). For periodicity, we found a peak of occurrence around the years 2000 and
      2003. CONCLUSION: The epidemiology of meningitis in Iran follows similar patterns
      of age, sex, and seasonality distribution as found in other countries and
      populations.

PMID- 20030847
TI  - Validation of internal reference genes for quantitative real-time PCR in a non
      model organism, the yellow-necked mouse, Apodemus flavicollis.
AB  - BACKGROUND: Reference genes are used as internal standards to normalize mRNA
      abundance in quantitative real-time PCR and thereby allow a direct comparison
      between samples. So far most of these expression studies used human or classical
      laboratory model species whereas studies on non-model organism under in-situ
      conditions are quite rare. However, only studies in free-ranging populations can
      reveal the effects of natural selection on the expression levels of functional
      important genes. In order to test the feasibility of gene expression studies in
      wildlife samples we transferred and validated potential reference genes that were
      developed for lab mice (Mus musculus) to samples of wild yellow-necked mice,
      Apodemus flavicollis. The stability and suitability of eight potential reference
      genes was accessed by the programs BestKeeper, NormFinder and geNorm. FINDINGS:
      Although the three programs used different algorithms the ranking order of
      reference genes was significantly concordant and geNorm differed in only one,
      NormFinder in two positions compared to BestKeeper. The genes ordered by their
      mean rank from the most to the least stable gene were: Rps18, Sdha, Canx, Actg1,
      Pgk1, Ubc, Rpl13a and Actb. Analyses of the normalization factor revealed best
      results when the five most stable genes were included for normalization.
      DISCUSSION: We established a SYBR green qPCR assay for liver samples of wild A.
      flavicollis and conclude that five genes should be used for appropriate
      normalization. Our study provides the basis to investigate differential
      expression of genes under selection under natural selection conditions in liver
      samples of A. flavicollis. This approach might also be applicable to other non
      model organisms.

PMID- 20030848
TI  - ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain.
AB  - BACKGROUND: ZnT3 is a membrane Zn(2+ )transporter that is responsible for
      concentrating Zn(2+ )into neuronal presynaptic vesicles. Zn(2+ )homeostasis in
      the brain is relevant to Alzheimer's disease (AD) because Zn(2+ )released during
      neurotransmission may bind to Abeta peptides, accelerating the assembly of Abeta
      into oligomers which have been shown to impair synaptic function. RESULTS: We
      quantified ZnT3 mRNA levels in Braak-staged human post mortem (pm) brain tissue
      from medial temporal gyrus, superior occipital gyrus, superior parietal gyrus,
      superior frontal gyrus and cerebellum from individuals with AD (n = 28), and
      matched controls (n = 5) using quantitative real-time PCR. ZnT3 mRNA levels were
      significantly decreased in all four cortical regions examined in the AD patients,
      to 45-60% of control levels. This reduction was already apparent at Braak stage 4
      in most cortical regions examined. Quantification of neuronal and glial-specific
      markers in the same samples (neuron-specific enolase, NSE; and glial fibrillary
      acidic protein, GFAP) indicated that loss of cortical ZnT3 expression was more
      pronounced, and occurred prior to, significant loss of NSE expression in the
      tissue. Significant increases in cortical GFAP expression were apparent as the
      disease progressed. No gene expression changes were observed in the cerebellum,
      which is relatively spared of AD neuropathology. CONCLUSIONS: This first study to
      quantify ZnT3 mRNA levels in human pm brain tissue from individuals with AD and
      controls has revealed a significant loss of ZnT3 expression in cortical regions,
      suggesting that neuronal cells in particular show reduced expression of ZnT3 mRNA
      in the disease. This suggests that altered neuronal Zn(2+ )handling may be an
      early event in AD pathogenesis.

PMID- 20030849
TI  - Factors associated with seroprevalence of hepatitis C among dentists at a large
      Brazilian city.
AB  - BACKGROUND: The aim of the present study was to investigate the seroprevalence
      and sociodemographic data, health-related and occupational factors and other
      correlates of sero-posivity among dentists in the city of Belo Horizonte, MG,
      Brazil. METHODS: A cross-sectional survey was carried out with 1302 dentists in
      Belo Horizonte, Brazil. All dentists were tested for anti-HCV using a
      commercially available enzyme-linked immunosorbent assay (ELISA). Individuals
      positive for anti-HCV were recalled for further evaluation. The presence of HCV
      RNA in anti-HCV-positive samples was assessed using reverse transcription
      polymerase chain reaction (RT-PCR). Data on demographic, behavioural and
      occupational exposure aspects were collected through questionnaires. RESULTS: The
      seroprevalence of anti-HCV was 0.9% (95% IC 0.5-1.7%). The factors associated to
      the prevalence of hepatitis C were history of blood transfusion (p = 0.002) and
      having undergone a test for hepatitis C (p = 0.015). CONCLUSIONS: The
      seroprevalence of anti-HCV among dentists is low. Moreover, no occupational
      exposure was associated to the seroprevalence of hepatitis C.

PMID- 20030850
TI  - "Getting your message through": an editorial guide for meeting publication
      standards.

PMID- 20030845
TI  - Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage.
AB  - Human immunodeficiency virus type 1 (HIV-1) has been shown to replicate
      productively in cells of the monocyte-macrophage lineage, although replication
      occurs to a lesser extent than in infected T cells. As cells of the monocyte
      macrophage lineage become differentiated and activated and subsequently travel to
      a variety of end organs, they become a source of infectious virus and secreted
      viral proteins and cellular products that likely initiate pathological
      consequences in a number of organ systems. During this process, alterations in a
      number of signaling pathways, including the level and functional properties of
      many cellular transcription factors, alter the course of HIV-1 long terminal
      repeat (LTR)-directed gene expression. This process ultimately results in events
      that contribute to the pathogenesis of HIV-1 infection. First, increased
      transcription leads to the upregulation of infectious virus production, and the
      increased production of viral proteins (gp120, Tat, Nef, and Vpr), which have
      additional activities as extracellular proteins. Increased viral production and
      the presence of toxic proteins lead to enhanced deregulation of cellular
      functions increasing the production of toxic cellular proteins and metabolites
      and the resulting organ-specific pathologic consequences such as neuroAIDS. This
      article reviews the structural and functional features of the cis-acting elements
      upstream and downstream of the transcriptional start site in the retroviral LTR.
      It also includes a discussion of the regulation of the retroviral LTR in the
      monocyte-macrophage lineage during virus infection of the bone marrow, the
      peripheral blood, the lymphoid tissues, and end organs such as the brain. The
      impact of genetic variation on LTR-directed transcription during the course of
      retrovirus disease is also reviewed.

PMID- 20030852
TI  - Overexpression of the ATP binding cassette gene ABCA1 determines resistance to
      Curcumin in M14 melanoma cells.
AB  - BACKGROUND: Curcumin induces apoptosis in many cancer cells and it reduces
      xenograft growth and the formation of lung metastases in nude mice. Moreover, the
      plant derived polyphenol has been reported to be able to overcome drug resistance
      to classical chemotherapy. These features render the drug a promising candidate
      for tumor therapy especially for cancers known for their high rates concerning
      therapy resistance like melanoma. RESULTS: We show here that the melanoma cell
      line M14 is resistant to Curcumin induced apoptosis, which correlates with the
      absence of any effect on NFkappaB signaling. We show that CXCL1 a chemokine that
      is down regulated in breast cancer cells by Curcumin in an NFkappaB dependent
      manner is expressed at variable levels in human melanomas. Yet in M14 cells,
      CXCL1 expression did not change upon Curcumin treatment. Following the hypothesis
      that Curcumin is rapidly removed from the resistant cells, we analyzed expression
      of known multi drug resistance genes and cellular transporters in M14 melanoma
      cells and in the Curcumin sensitive breast cancer cell line MDA-MB-231. ATP
      binding cassette transporter ABCA1, a gene involved in the cellular lipid removal
      pathway is over-expressed in resistant M14 melanoma as compared to the sensitive
      MDA-MB-231 breast cancer cells. Gene silencing of ABCA1 by siRNA sensitizes M14
      cells to the apoptotic effect of Curcumin most likely as a result of reduced
      basal levels of active NFkappaB. Moreover, ABCA1 silencing alone also induces
      apoptosis and reduces p65 expression. CONCLUSION: Resistance to Curcumin thus
      follows classical pathways and ABCA1 expression should be considered as response
      marker.

PMID- 20030851
TI  - New targets for the treatment of follicular lymphoma.
AB  - The last two decades have witnessed striking advances in our understanding of the
      biological factors underlying the development of Follicular lymphoma (FL).
      Development of newer treatment approaches have improved the outlook for many
      individuals with these disorders; however, with these advances come new
      questions. Given the long-term survival of patients with FL, drugs with
      favourable side-effect profile and minimal long-term risks are desired. FL is
      incurable with current treatment modalities. It often runs an indolent course
      with multiple relapses and progressively shorter intervals of remission. The
      identification of new targets and development of novel targeted therapies is
      imperative to exploit the biology of FL while inherently preventing relapse and
      prolonging survival. This review summarizes the growing body of knowledge
      regarding novel therapeutic targets, enabling the concept of individualized
      targeted therapy for the treatment of FL.

PMID- 20030853
TI  - Antioxidant enzymes and lipid peroxidation in endometrium of patients with
      polyps, myoma, hyperplasia and adenocarcinoma.
AB  - BACKGROUND: Oxidative stress and impaired antioxidant system have been proposed
      as a potential factors involved in the pathophysiology of diverse disease states,
      including carcinogenesis. In this study, we explored the lipid peroxidation
      levels and antioxidant enzyme activities in women diagnosed with different forms
      of gynecological diseases in order to evaluate the antioxidant status in
      endometrium of such patients. METHODS: Endometrial tissues of gynecological
      patients with different diagnoses were collected and subjected to assays for
      superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and
      lipid hydroperoxides. RESULTS: Superoxide dismutase activity was significantly
      decreased (50% in average) in hyperplastic and adenocarcinoma patients.
      Activities of both glutathione peroxidase and glutathione reductase were
      increased 60% and 100% on average, in hyperplastic patients, while in
      adenocarcinoma patients only glutathione reductase activity was elevated 100%.
      Catalase activity was significantly decreased in adenocarcinoma patients (47%).
      Lipid hydroperoxides level was negatively correlated to superoxide dismutase and
      catalase activities, and positively correlated to glutathione peroxidase and
      glutathione reductase activities. CONCLUSIONS: This study provided the first
      comparison of antioxidant status and lipid peroxidation in endometrial tissues of
      patients with polyps, myoma, hyperplasia and adenocarcinoma. The results showed
      that patients with premalignant (hyperplastic) and malignant (adenocarcinoma)
      lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme
      activities than patients with benign uterine diseases, polyps and myoma, although
      the extent of disturbance varied with the diagnosis. Further investigation is
      needed to clarify the mechanisms responsible for the observed alterations and
      whether lipid hydroperoxide levels and antioxidant enzyme activities in uterus of
      gynecological patients might be used as additional parameter in clinical
      evaluation of gynecological disorders.

PMID- 20030854
TI  - The GYMSSA trial: a prospective randomized trial comparing gastrectomy,
      metastasectomy plus systemic therapy versus systemic therapy alone.
AB  - BACKGROUND: The standard of care for metastatic gastric cancer (MGC) is systemic
      chemotherapy which leads to a median survival of 6-15 months. Survival beyond 3
      years is rare. For selected groups of patients with limited MGC, retrospective
      studies have shown improved overall survival following gastrectomy and
      metastasectomies including peritoneal stripping with continuous hyperthermic
      peritoneal perfusion (CHPP), liver resection, and pulmonary resection. Median
      survival after liver resection for MGC is up to 34 months, with a five year
      survival rate of 24.5%. Similarly, reported median survival after pulmonary
      resection of MGC is 21 months with long term survival of greater than 5 years a
      possibility. Several case reports and small studies have documented evidence of
      long-term survival in select individuals who undergo CHPP for MGC. DESIGN: The
      GYMSSA trial is a prospective randomized trial for patients with MGC. It is
      designed to compare two therapeutic approaches: gastrectomy with metastasectomy
      plus systemic chemotherapy (GYMS) versus systemic chemotherapy alone (SA).
      Systemic therapy will be composed of the FOLFOXIRI regimen. The aim of the study
      is to evaluate overall survival and potential selection criteria to determine
      those patients who may benefit from surgery plus systemic therapy. The study will
      be conducted by the Surgery Branch at the National Cancer Institute (NCI),
      National Institutes of Health (NIH) in Bethesda, Maryland. Surgeries and followup
      will be done at the NCI, and chemotherapy will be given by either the local
      oncologist or the medical oncology branch at NCI. TRIAL REGISTRATION:
      ClinicalTrials.gov ID. NCT00941655.

PMID- 20030855
TI  - Design and baseline characteristics of a prospective cohort study for
      determinants of osteoporotic fracture in community-dwelling elderly Japanese men:
      the Fujiwara-kyo osteoporosis risk in men (FORMEN) study.
AB  - BACKGROUND: Osteoporosis and osteoporotic fracture in men are significant public
      health problems in an aging society. However, information on male osteoporosis
      remains impressively lacking, especially for Asians. We designed the Fujiwara-kyo
      Osteoporosis Risk in Men (FORMEN) study as an ancillary study of a cohort study,
      the Fujiwara-kyo study, to determine risk factors for osteoporotic fractures in
      Japanese men. METHODS/DESIGN:  DESIGN: A community-based single-centre
      prospective cohort study with at least a 5-year follow-up. SUBJECTS: All the male
      participants of the Fujiwara-kyo study who were living in the four cities
      studied, aged 65 years and older, and able to walk without aid from others.
      PRIMARY OUTCOME: Incidence of osteoporotic fractures including vertebral and
      clinical non-vertebral fractures. ADDITIONAL OUTCOMES: Change in bone mineral
      density (BMD), change in hip geometry, onset of receiving benefits from Long-term
      Care Insurance (LCI), health-related quality of life, and mortality. BASELINE
      MEASUREMENTS: BMD at the lumbar spine (LS) and hip (TH), hip geometry, vertebral
      deformity assessment, bone turnover markers, physical and cognitive performance,
      various medical and lifestyle factors, and geriatric psychosocial measures
      confirmed by interviews based on self-administrated questionnaires.OUTCOME
      SURVEILLANCE: Annual mail surveys and a follow-up survey at the fifth year
      comprising similar items to the baseline study will be used to determine the
      outcomes. Receipt of benefits from LCI and mortality will be obtained from the
      city governments. CURRENT STATUS: The baseline study was conducted for 2174
      eligible men, and 2012 completed the study and were eligible for follow-up.
      Prevalence rates of osteoporosis (BMD 2.5 SD or more below the young adult mean
      (YAM)) and low BMD (BMD 1 SD or more below YAM) in at least one of LS and TH were
      calculated to be 4.4% and 41.8%, respectively. The proportion of men with low BMD
      only at TH showed a significant increasing trend with aging (p < 0.0001) while
      that only at LS showed a decreasing trend (p = 0.0386). The prevalence rate of
      osteoporosis was underestimated when diagnosed using only BMD at LS. Other
      baseline measurements were successfully obtained. DISCUSSION: FORMEN baseline
      study was performed as designed and the FORMEN cohort study was successfully
      launched.

PMID- 20030856
TI  - Management of gastro-bronchial fistula complicating a subtotal esophagectomy: a
      case report.
AB  - BACKGROUND: The development of a fistula between the tracheobronchial tree and
      the gastric conduit post esophagectomy is a rare and often fatal complication.
      CASE PRESENTATION: A 68 year old man underwent radical esophagectomy for
      esophageal adenocarcinoma. On postoperative day 14 the nasogastric drainage bag
      dramatically filled with air, without deterioration in respiratory function or
      progressive sepsis. A fiberoptic bronchoscopy was performed which demonstrated a
      gastro-bronchial fistula in the posterior aspect of the left main bronchus. He
      was managed conservatively with antibiotics, enteral nutrition via jejunostomy,
      and non-invasive respiratory support. A follow- up bronchoscopy 60 days after the
      diagnostic bronchoscopy, confirmed spontaneous closure of the fistula
      CONCLUSIONS: This is the first such case where a conservative approach with no
      surgery or endoprosthesis resulted in a successful outcome, with fistula closure
      confirmed at subsequent bronchoscopy. Our experience would suggest that in very
      carefully selected cases where bronchopulmonary contamination from the fistula is
      minimal or absent, there is no associated inflammation of the tracheobronchial
      tree and the patient is stable from a respiratory point of view without evidence
      of sepsis, there may be a role for a trial of conservative management.

PMID- 20030857
TI  - LipocalinPred: a SVM-based method for prediction of lipocalins.
AB  - BACKGROUND: Functional annotation of rapidly amassing nucleotide and protein
      sequences presents a challenging task for modern bioinformatics. This is
      particularly true for protein families sharing extremely low sequence identity,
      as for lipocalins, a family of proteins with varied functions and great diversity
      at the sequence level, yet conserved structures. RESULTS: In the present study we
      propose a SVM based method for identification of lipocalin protein sequences. The
      SVM models were trained with the input features generated using amino acid,
      dipeptide and secondary structure compositions as well as PSSM profiles. The
      model derived using both PSSM and secondary structure emerged as the best model
      in the study. Apart from achieving a high prediction accuracy (>90% in leave-one
      out), lipocalinpred correctly differentiates closely related fatty acid-binding
      proteins and triabins as non-lipocalins. CONCLUSION: The method offers a
      promising approach as a lipocalin prediction tool, complementing PROSITE, Pfam
      and homology modelling methods.

PMID- 20030858
TI  - Downregulation of protein kinase C-alpha enhances intracellular survival of
      Mycobacteria: role of PknG.
AB  - BACKGROUND: Intracellular trafficking of mycobacteria is comprehensively
      dependent on the unusual regulation of host proteins. Recently, we have reported
      that infection of macrophages by Mycobacterium tuberculosis H37Rv (Rv)
      selectively downregulates the expression of PKCalpha while infection by
      Mycobacterium smegmatis (MS) does not. RESULTS: Based on our earlier study, we
      have extrapolated for the first time that knockdown of PKCalpha, impairs
      phagocytosis of mycobacteria by macrophages while their intracellular survival is
      drastically increased. Mycobacterium bovis BCG (BCG) and Mycobacterium
      tuberculosis H37Ra (Ra) have also been shown to downregulate the expression of
      PKCalpha during the infection. Since PknG is uniquely expressed in BCG, Ra, Rv
      but not in MS and has been reported to promote intracellular survival of
      mycobacteria, led us to believe that PknG may be involved in such downregulation
      of PKCalpha. THP-1 cells infected with recombinant MS expressing PknG (MS-G),
      showed significant reduction in PKCalpha expression. In normal THP-1 cells
      survival of MS-G was enhanced as compared to MS, while their behavior in PKCalpha
      deficient cells could not be distinguished. The results strongly demonstrate that
      pathogenic mycobacteria recognize and then inhibit PKCalpha to circumvent
      phagocytosis and the hostile environment of macrophages. We emphasize that, this
      inhibition is controlled by PknG. CONCLUSIONS: All together, our data reveal a
      mechanism that shows substantial interdependence of PKCalpha with PknG, in
      sustaining mycobacterial infection.

PMID- 20030859
TI  - Study on the evaluation of the clinical effects of traditional chinese medicine
      in heart failure by complex intervention: protocol of SECETCM-HF.
AB  - BACKGROUND: Experts in Traditional Chinese Medicine (TCM) have studied the TCM
      subject of the pathogenesis of heart failure (HF) for several decades. As a
      result, the general idea is ben deficiency and biao excess. However, the clinical
      evaluation system which combined the TCM and western medicine in HF has not been
      developed yet. The objective is to establish the evaluation index system for the
      integration of TCM and western medicine. The evaluation indexes which include TCM
      items will specify the research design and methods. METHODS: Nine medical centers
      in different cities in China will participate in the trial. A population of 340
      patients with HF will be enrolled through a central randomized system for
      different test groups. Group A will be treated with only western medicine, while
      group B with western and Chinese medicine together. The study will last for 12
      months from the date of enrollment. The cardiovascular death will be the primary
      outcome. DISCUSSION: By putting the protocol into practice, the clinical effects
      of TCM for HF will be identified scientifically, objectively as well as
      rationally. The proper index system which built in the study will be helpful for
      the clinical effect expression of HF by integrated medicine in future. TRIAL
      REGISTRATION: ChiCTR-TRC-00000059.

PMID- 20030860
TI  - Controversies in breast cancer 2009.

PMID- 20030862
TI  - Gene expression profiling of breast cancer.

PMID- 20030861
TI  - Clinical relevance and current challenges of research on disseminating tumor
      cells in cancer patients.

PMID- 20030863
TI  - Next-generation sequencing.
AB  - Next-generation sequencing (also known as massively parallel sequencing)
      technologies are revolutionising our ability to characterise cancers at the
      genomic, transcriptomic and epigenetic levels. Cataloguing all mutations, copy
      number aberrations and somatic rearrangements in an entire cancer genome at base
      pair resolution can now be performed in a matter of weeks. Furthermore, massively
      parallel sequencing can be used as a means for unbiased transcriptomic analysis
      of mRNAs, small RNAs and noncoding RNAs, genome-wide methylation assays and high
      throughput chromatin immunoprecipitation assays. Here, I discuss the potential
      impact of this technology on breast cancer research and the challenges that come
      with this technological breakthrough.

PMID- 20030864
TI  - Who would have thought it! Influence on outcome of radiotherapy, Ki67 and stroma.
      Introduction to Session 5.

PMID- 20030865
TI  - Radiation impact in breast cancer.

PMID- 20030866
TI  - Who would have thought a single Ki67 measurement would predict long-term outcome?

PMID- 20030867
TI  - Breast tumour stroma is a prognostic indicator and target for therapy.

PMID- 20030868
TI  - Introduction to sessions on guidelines and endocrine therapy, the influence of
      breast screening on number of mastectomies and the challenge between molecular
      science and traditional dogma in the treatment of breast cancer. Introduction to
      Session 6.

PMID- 20030869
TI  - Do BIG1-98 and ZOFAST demand a change in guidelines for endocrine therapy?

PMID- 20030870
TI  - Breast screening has increased the number of mastectomies.

PMID- 20030871
TI  - Risk factors. Introduction to Session 1.

PMID- 20030872
TI  - Are current drug development programmes realising the full potential of new
      agents? Introduction to Sessions 7 and 8.

PMID- 20030873
TI  - Are current drug development programmes realising the full potential of new
      agents? The scenario.

PMID- 20030874
TI  - The role of preclinical animal models in breast cancer drug development.

PMID- 20030875
TI  - Foundation clinical trials.

PMID- 20030876
TI  - Are current drug development programmes realising the full potential of new
      agents? Tyrosine kinase inhibitors.

PMID- 20030877
TI  - Controversies in breast cancer: the mammalian target of rapamycin as a target for
      breast cancer therapy.

PMID- 20030878
TI  - Alcohol consumption and breast cancer risk.

PMID- 20030879
TI  - Mammographic density.

PMID- 20030880
TI  - Underarm antiperspirants/deodorants and breast cancer.

PMID- 20030881
TI  - Debate: tailored targeted therapy for all--a realistic and worthwhile objective?
      Introduction to Session 2.

PMID- 20030882
TI  - Tailored targeted therapy for all: a realistic and worthwhile objective?

PMID- 20030883
TI  - Tailored targeted therapy for all: a realistic and worthwhile objective against.

PMID- 20030884
TI  - The potential of new technologies/approaches. Introduction to Sessions 3 and 4.

PMID- 20030885
TI  - Practical tools and methods for health technology assessment in Europe:
      structures, methodologies, and tools developed by the European Network for Health
      Technology Assessment, EUnetHTA.
AB  - OBJECTIVES: This article presents an overview of the practical methods and tools
      to support transnational Health Technology Assessment (HTA) that were developed
      and pilot tested by the European network for HTA (EUnetHTA), which involved a
      total of sixty-four Partner organizations. METHODS: The methods differ according
      to scope and purpose of each of the tools developed. They included, for example,
      literature reviews, surveys, Delphi and consensus methods, workshops, pilot
      tests, and internal/public consultation. RESULTS: Practical results include an
      HTA Core Model and a Handbook on the use of the model, two pilot examples of HTA
      core information, an HTA Adaptation Toolkit for taking existing reports into new
      settings, a book about HTA and health policy making in Europe, a newsletter
      providing structured information about emerging/new technologies, an interactive
      Web-based tool to share information about monitoring activities for emerging/new
      technologies, and a Handbook on HTA capacity building for Member States with
      limited institutionalization of HTA. CONCLUSIONS: The tools provide high-quality
      information and methodological frameworks for HTA that facilitate preparation of
      HTA documentation, and sharing of information in and across national or regional
      systems. The tools will be used and further tested by partners in the EUnetHTA
      Collaboration aiming to (i) help reduce unnecessary duplication of HTA
      activities, (ii) develop and promote good practice in HTA methods and processes,
      (iii) share what can be shared, (iv) facilitate local adaptation of HTA
      information, (v) improve the links between health policy and HTA.

PMID- 20030886
TI  - The HTA core model: a novel method for producing and reporting health technology
      assessments.
AB  - OBJECTIVES: The aim of this study was to develop and test a generic framework to
      enable international collaboration for producing and sharing results of health
      technology assessments (HTAs). METHODS: Ten international teams constructed the
      HTA Core Model, dividing information contained in a comprehensive HTA into
      standardized pieces, the assessment elements. Each element contains a generic
      issue that is translated into practical research questions while performing an
      assessment. Elements were described in detail in element cards. Two pilot
      assessments, designated as Core HTAs were also produced. The Model and Core HTAs
      were both validated. Guidance on the use of the HTA Core Model was compiled into
      a Handbook. RESULTS: The HTA Core Model considers health technologies through
      nine domains. Two applications of the Model were developed, one for medical and
      surgical interventions and another for diagnostic technologies. Two Core HTAs
      were produced in parallel with developing the model, providing the first real
      life testing of the Model and input for further development. The results of
      formal validation and public feedback were primarily positive. Development needs
      were also identified and considered. An online Handbook is available.
      CONCLUSIONS: The HTA Core Model is a novel approach to HTA. It enables effective
      international production and sharing of HTA results in a structured format. The
      face validity of the Model was confirmed during the project, but further testing
      and refining are needed to ensure optimal usefulness and user-friendliness. Core
      HTAs are intended to serve as a basis for local HTA reports. Core HTAs do not
      contain recommendations on technology use.

PMID- 20030887
TI  - Testing the HTA core model: experiences from two pilot projects.
AB  - OBJECTIVES: The aim of this study was to analyze and describe process and
      outcomes of two pilot assessments based on the HTA Core Model, discuss the
      applicability of the model, and explore areas of development. METHODS: Data were
      gathered from HTA Core Model and pilot Core HTA documents, their validation
      feedback, questionnaires to investigators, meeting minutes, emails, and
      discussions in the coordinating team meetings in the Finnish Office for Health
      Technology Assessment (FINOHTA). RESULTS: The elementary structure of the HTA
      Core Model proved useful in preparing HTAs. Clear scoping and good coordination
      in timing and distribution of work would probably help improve applicability and
      avoid duplication of work. CONCLUSIONS: The HTA Core Model can be developed into
      a platform that enables and encourages true HTA collaboration in terms of
      distribution of work and maximum utilization of a common pool of structured HTA
      information for national HTA reports.

PMID- 20030888
TI  - The adaptation of health technology assessment reports: identification of the
      need for, and development of, a toolkit to aid the process.
AB  - OBJECTIVES: Europe has many health technology assessment (HTA) agencies, each
      producing their own HTA reports. Adapting HTA reports for different contexts
      could reduce the need for multiple reports on the same health technology with
      resultant saving of time and resources. This study aims to examine and understand
      the process of adaptation, and to develop a toolkit that would help the
      adaptation of reports produced by other countries. METHODS: The methods used were
      a review of the literature; a survey of twenty-nine European HTA organizations,
      two rounds of a Delphi survey, a face-to-face meeting of twenty-one European
      network for Health Technology Assessment (EUnetHTA) representatives, iterative
      rounds of review, and two rounds of quality assurance testing (termed
      applicability testing). RESULTS: Descriptions of previous examples of adaptation
      in the literature are sparse. Most respondents had previous experience in
      adapting reports, and all believed that adaptation was useful, and there was the
      ability to benefit from the use of a toolkit to aid in the process. EUnetHTA
      Partners developed and tested an adaptation toolkit. The toolkit is composed of a
      series of checklists and resources that identify or clarify the relevance,
      reliability, and transferability of data and information from existing reports.
      CONCLUSIONS: Consensus of opinion from twenty-nine European
      organizations/networks has indicated that the adaptation of HTA reports would be
      desirable and beneficial. A toolkit was developed to help with the adaptation of
      HTA reports produced in other settings. This collection of resources is available
      for use by all HTA agencies and can be accessed at:
      http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf.

PMID- 20030889
TI  - The health technology assessment adaptation toolkit: description and use.
AB  - OBJECTIVES: Adapting health technology assessment (HTA) reports for different
      contexts could reduce the need for multiple reports on the same health technology
      with resultant saving of time and resources. This article describes an
      instrument, the adaptation toolkit, which has been developed to aid in the
      process of adaptation of HTA reports. METHODS: The toolkit was developed by a
      partnership of HTA agencies and networks from across Europe. The role of the
      toolkit is to guide the user through the process of selecting possible relevant
      material from these report(s), assessing the relevance, reliability, and
      transferability of the material, and adapting it for the desired context.
      RESULTS: The adaptation toolkit has been developed, it comprises a collection of
      resources that help the user assess whether data and information in existing HTA
      reports should and could be adapted for their own setting. The toolkit contains
      two sections: a preliminary speedy sifting section and the main toolkit. The main
      toolkit includes five domains: (i) technology use and development, (ii) safety,
      (iii) effectiveness (including efficacy), (iv) economic evaluation, and (v)
      organizational aspects. Legal, ethical, and social aspects are beyond the scope
      of the toolkit. The toolkit is designed for the adaptation of evidence synthesis
      rather than primary research. CONCLUSIONS: The completed current version of the
      toolkit contains checklists and resources to aid in the adaptation of HTA
      reports. This collection of resources is available for use by all HTA agencies
      and can be accessed at:
      http://www.eunethta.net/upload/WP5/EUnetHTA_HTA_Adaptation_Toolkit_October08.pdf.

PMID- 20030890
TI  - Enhancing understanding: the development of a glossary of health technology
      assessment adaptation terms.
AB  - BACKGROUND: The way people use health technology assessment (HTA) terms varies
      considerably across Europe. Such variation can lead to misunderstandings when
      reading HTA reports from different contexts. This work is one of the outputs of
      the EUnetHTA Project and was undertaken between 2006 and 2008. OBJECTIVES: The
      aim of this study was to develop a glossary of HTA adaptation terms to help
      reduce the misunderstandings of terms used in HTA reports from contexts other
      than the reader's own. METHODS: Several HTA glossaries were examined to identify
      ways in which an additional glossary could offer readers something new and to
      identify adaptation terms for inclusion. Twenty-eight European HTA organizations
      provided terms for the glossary and drafted descriptions and examples of how each
      specific term was used in their particular setting. The organizations then
      commented on the descriptions provided by the other groups and worked together to
      draft a single description for certain terms. RESULTS: A glossary of HTA
      adaptation terms was developed. It provides a comprehensive range of
      descriptions, examples, and comments for forty-two potentially confusing HTA
      terms related to adaptation. CONCLUSIONS: This glossary will be a valuable
      resource for European HTA agencies when reading HTA reports produced in different
      contexts and for adapting HTA reports produced in other countries. The glossary
      will help improve understanding and help facilitate the adaptation process.

PMID- 20030891
TI  - Information service on new and emerging health technologies: identification and
      prioritization processes for a European union-wide newsletter.
AB  - OBJECTIVES: EUnetHTA WP 7 (Strand B) aimed to promote sharing information on new
      and emerging technologies. The task was to develop a prototype of a newsletter
      and pilot the processes of production. METHODS: The EuroScan database served as
      information source on pertinent technologies. To prioritize, a set of criteria
      for scoring the potential impact and for selecting the technologies for articles
      was applied and a pilot newsletter was produced. RESULTS: Being objective and
      transparent about the content of a newsletter required a method for prioritizing
      health technologies. Using significance criteria, members of the prioritization
      panel selected twelve technologies for articles of different length and depth.
      Potential recipients, surveyed on relevance, content, timeliness, and readability
      responded mostly positive, but requested more information on cost effectiveness
      and criticized timeliness. CONCLUSIONS: Dissemination of an EU-wide newsletter
      would be feasible, but time-consuming. Although a newsletter appears to fulfill a
      need for information on emerging and new health technologies, it is not
      considered the right tool to avoid duplication of effort in the present
      international constellation of horizon scanning for new health technologies.
      Other options will be pursued as part of future collaborative actions, for
      example, a core set of early awareness information, or an on-demand electronic
      information system.

PMID- 20030892
TI  - A common policy framework for evidence generation on promising health
      technologies.
AB  - BACKGROUND: Generation of additional evidence may be necessary to access new
      promising technologies (marketing approval or coverage). Access with evidence
      generation (AEG) is a more recent concept with regard to coverage than to
      marketing approval. OBJECTIVES: One aim of Work Package 7 (WP7) Strand A of the
      European network for Health Technology Assessment (EUnetHTA) was to provide an
      overview of national AEG mechanisms associated with marketing approvals and
      funding or coverage decisions. METHODS: A systematic literature review, surveys
      of WP7 Partners, and consultation of key people were used to obtain information
      on the AEG mechanisms used by twenty-three countries (twenty European countries,
      United States, Canada [Ontario], and Australia). RESULTS: Interest in the
      implementation of AEG policies, particularly at the coverage decision stage, is
      growing. An overview of national experiences was used to draw up a generally
      applicable five-step policy framework for AEG mechanisms that comprised (i) a
      first assessment identifying knowledge gaps; (ii) a decision conditional to
      evidence generation; (iii) generation of the evidence requested; (iv) re
      assessment integrating the new evidence; (v) a revised decision. The critical
      factors for success that were identified were coordination, methodological
      guidance, funding, and a regulatory framework. Countries were categorized on the
      basis of current implementation of the proposed policy framework. CONCLUSIONS:
      International collaboration is necessary to gather a critical mass of high
      quality data quickly and to ensure timely access to new promising technologies.
      The overview produced by WP7A has led to development of tools to facilitate
      collaboration on evidence generation.

PMID- 20030893
TI  - Web-based toolkit to facilitate European collaboration on evidence generation on
      promising health technologies.
AB  - BACKGROUND: Several countries have developed policy frameworks allowing timely
      access to promising health technologies on the condition that additional evidence
      is generated. However, an important barrier to evidence generation is the lack of
      structured collaboration among health technology assessment (HTA) agencies.
      OBJECTIVES: One of the aims of Work Package 7 (WP7) of the European network for
      Health Technology Assessment (EUnetHTA) Project was to determine the types of
      structured collaboration that could facilitate evidence generation and to develop
      a Web-based toolkit to support such collaboration. METHODS: Collaboration
      modalities were defined by all WP7 Partners. Initial emphasis was on information
      sharing. Standardized forms for information sharing were developed and tested. An
      information technology development phase followed with the creation of the Web
      based toolkit (Web site). RESULTS: Three levels of collaboration were agreed on:
      (i) sharing information, (ii) coordinated action, and (iii) joint action. The Web
      site allows access to structured and standardized forms for requesting
      information, posting information in response to a request, and posting
      information spontaneously. An online database contains all of the information
      requested or posted. Pilot tests on twenty-one promising technologies were
      satisfactory. CONCLUSIONS: This new Web site for sharing information on evidence
      generation should help countries reach robust decisions on the timely adoption of
      promising health technologies. It will only become fully operational if EUnetHTA
      Partners supply relevant, accurate, and updated information, and regularly use
      the Web site.

PMID- 20030894
TI  - Systems to support health technology assessment (HTA) in member states of the
      European union with limited institutionalization of HTA.
AB  - OBJECTIVES: The aim of this study was to support health technology assessment
      (HTA) capacity building in Member States of the European Union with limited
      experience or without institutionalized HTA. The main output is a Handbook on HTA
      Capacity Building. METHODS: The methods used were worldwide surveys of (i) HTA
      organizations, (ii) information management units, and (iii) HTA educational
      programs. The results of two surveys (i & ii) were combined with expert opinion
      to produce the Handbook on HTA Capacity Building. RESULTS: Survey of HTA
      organizations (n = 41, response rate 35 percent). Most of the organizations were
      established by the government (61 percent), and all were not-for-profit. Working
      on HTA (80.5 percent) and doing research (63.4 percent) were the main lines of
      activity. Survey on information management units (n = 23, response rate 23
      percent). Most (74.2 percent) of the responding HTA agencies reported having
      personnel dedicated to HTA information services. Survey on HTA educational
      programs (n = 48, response rate 60 percent). In total, nine Master of Science
      (MSc) programs were identified (three MSc in HTA and six MSc in HTA-related
      areas). Handbook on HTA Capacity Building. A group of twenty experts from
      thirteen countries developed the handbook. It consists of nine chapters focusing
      on HTA institutional development (structural setup, work processes, and
      visibility). CONCLUSIONS: Setting up organizational structures and establishing
      effective HTA programs that guide key policy decisions is a challenging task.
      There are no standard models or pathways. "One size fits all" is not a useful
      principle because of the wide systemic and cultural differences between
      countries. The Handbook on HTA Capacity Building includes approaches for overall
      institutional development, especially in formulating objectives, setting up
      structures, and defining work processes.

PMID- 20030895
TI  - Involving stakeholders and developing a policy for stakeholder involvement in the
      European network for health technology assessment, EUnetHTA.
AB  - OBJECTIVES: This article explains how the issue of stakeholder involvement was
      addressed in the European network for Health Technology Assessment (EUnetHTA)
      Project and describes the structures of future stakeholder involvement in the
      EUnetHTA Collaboration. METHODS: Initiatives led to a dialogue with stakeholders
      and exchanging views and expectations on health technology assessment (HTA)
      processes and the future development of EUnetHTA. The methods of involving
      different stakeholder groups in EUnetHTA included general information to
      stakeholders about EUnetHTA, targeted information on a Web site, analysis of
      stakeholder opinions on HTA and EUnetHTA, and development of a draft stakeholder
      policy. RESULTS: First steps were taken to organize processes to consolidate the
      legitimacy of EUnetHTA and its products and encourage the representation of
      interests, thus contributing to promoting the utilization of HTA in
      national/regional policy making. A stakeholder Web site, analyses of stakeholder
      opinions on HTA and EUnetHTA in a discussion topic catalog, and a draft
      stakeholder policy resulted from the work. CONCLUSIONS: Stakeholder involvement
      in EUnetHTA is necessary to ensure the legitimacy and prospects for utilization
      of EUnetHTA and its products. The described activities and results create the
      foundation for a continued dialogue with, and involvement of, stakeholders. The
      EUnetHTA stakeholder meeting can be considered as a successful experience of
      dialogue between EUnetHTA and stakeholders, which should be continued. Our
      experience shows the challenge of obtaining balanced stakeholder representation
      across the identified stakeholder groups. Continued attention should be given to
      achieving balanced stakeholder representation.

PMID- 20030896
TI  - Toward a new information infrastructure in health technology assessment:
      communication, design, process, and results.
AB  - OBJECTIVES: The aim of this study was to facilitate effective internal and
      external communication of an international network and to explore how to support
      communication and work processes in health technology assessment (HTA). STRUCTURE
      AND METHODS: European network for Health Technology Assessment (EUnetHTA)
      connected sixty-four HTA Partner organizations from thirty-three countries. User
      needs in the different steps of the HTA process were the starting point for
      developing an information system. A step-wise, interdisciplinary, creative
      approach was used in developing practical tools. RESULTS: An Information Platform
      facilitated the exchange of scientific information between Partners and with
      external target groups. More than 200 virtual meetings were set up during the
      project using an e-meeting tool. A Clearinghouse prototype was developed with the
      intent to offering a single point of access to HTA relevant information. This
      evolved into a next step not planned from the outset: Developing a running HTA
      Information System including several Web-based tools to support communication and
      daily HTA processes. A communication strategy guided the communication effort,
      focusing on practical tools, creating added value, involving stakeholders, and
      avoiding duplication of effort. CONCLUSIONS: Modern technology enables a new
      information infrastructure for HTA. The potential of information and
      communication technology was used as a strategic tool. Several target groups were
      represented among the Partners, which supported collaboration and made it easier
      to identify user needs. A distinctive visual identity made it easier to gain and
      maintain visibility on a limited budget.

PMID- 20030897
TI  - Internal evaluation of the European network for health technology assessment
      project.
AB  - OBJECTIVES: The internal evaluation studied the development of the European
      network for Health Technology Assessment (EUnetHTA) Project in achieving the
      general objective of establishing an effective and a sustainable network of
      health technology assessment (HTA) in Europe. METHODS: The Work Package 3 group
      was dedicated to this task and performed the work. Information on activities
      during the project was collected from three sources. First, three yearly cross
      sectional studies surveyed the participants' opinions. Responses were by
      individuals or by institutions. The last round included surveys to the Steering
      Committee, the Stakeholder Forum, and the Secretariat. Second, the Work Package
      Lead Partners were interviewed bi-annually, five times in total, to update the
      information on the Project's progress. Third, additional information was sought
      in available documents. RESULTS: The organizational structure remained stable.
      The Project succeeded in developing tools aimed at providing common methodology
      with intent to establish a standard of conducting and reporting HTA and to
      facilitate greater collaboration among agencies. The participants/agencies
      expressed their belief in a network and in maintaining local/national autonomy.
      The Work Package Leaders expressed a strong belief in the solid base of the
      Project for a future network on which to build, but were aware of the need for
      funding and governmental support. CONCLUSIONS: Participants and Work Package
      Leaders have expressed support for a future network that will improve national
      and international collaboration in HTA based on the experience from the EUnetHTA
      project.

PMID- 20030898
TI  - European network for health technology assessment, EUnetHTA: planning,
      development, and implementation of a sustainable European network for health
      technology assessment.
AB  - OBJECTIVES: The European network on Health Technology Assessment (EUnetHTA) aimed
      to produce tangible and practical results to be used in the various phases of
      health technology assessment and to establish a framework and processes to
      support this. This article presents the background, objectives, and organization
      of EUnetHTA, which involved a total of sixty-four partner organizations. METHODS:
      Establishing an effective and sustainable structure for a transnational network
      involved many managerial, policy, and methodological tools, according to the
      objective of each task or Work Package. Transparency in organization, financial
      transactions, and decision making was a key principle in the management of the
      Project as was the commitment to appropriately involve stakeholders. RESULTS:
      EUnetHTA activities resulted in a clear management and governance structure,
      efficient partnership, and transnational cooperation. The Project developed a
      model for sustainable continuation of the EUnetHTA Collaboration. CONCLUSIONS:
      The EUnetHTA Project achieved its goals by producing a suite of practical tools,
      a strong network, and plans for continuing the work in a sustainable EUnetHTA
      Collaboration that facilitates and promotes the use of HTA at national and
      regional levels. Responsiveness to political developments in Europe should be
      balanced with maintaining a high level of ambition to promote independent,
      evidence-based information and well-tested tools for best practice based on a
      strong network of HTA institutions.

PMID- 20030899
TI  - Epicatechin induces NF-kappaB, activator protein-1 (AP-1) and nuclear
      transcription factor erythroid 2p45-related factor-2 (Nrf2) via
      phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular
      regulated kinase (ERK) signalling in HepG2 cells.
AB  - The dietary flavonoid epicatechin has been reported to exhibit a wide range of
      biological activities. The objective of the present study was to investigate the
      time-dependent regulation by epicatechin on the activity of the main
      transcription factors (NF-kappaB, activator protein-1 (AP-1) and nuclear
      transcription factor erythroid 2p45-related factor (Nrf2)) related to antioxidant
      defence and survival and proliferation pathways in HepG2 cells. Treatment of
      cells with 10 microm-epicatechin induced the NF-kappaB pathway in a time
      dependent manner characterised by increased levels of IkappaB kinase (IKK) and
      phosphorylated inhibitor of kappaB subunit-alpha (p-IkappaBalpha) and proteolytic
      degradation of IkappaB, which was consistent with an up-regulation of the NF
      kappaB-binding activity. Time-dependent activation of the AP-1 pathway, in
      concert with enhanced c-Jun nuclear levels and induction of Nrf2 translocation
      and phosphorylation were also demonstrated. Additionally, epicatechin-induced NF
      kappaB and Nrf2 were connected to reactive oxygen species intracellular levels
      and to the activation of cell survival and proliferation pathways, being
      phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular
      regulated kinase (ERK) associated to Nrf2 modulation and ERK to NF-kappaB
      induction. These data suggest that the epicatechin-induced survival effect occurs
      by the induction of redox-sensitive transcription factors through a tight
      regulation of survival and proliferation pathways.

PMID- 20030900
TI  - Detection of mastitis and its stage of progression by automatic milking systems
      using artificial neural networks.
AB  - Two types of artificial neural networks, multilayer perceptron (MLP) and self
      organizing feature map (SOM) were used to detect mastitis by automatic milking
      systems (AMS) using a new mastitis indicator that combined two previously
      reported indicators based on higher electrical conductivity (EC) and lower
      quarter yield (QY). Four MLPs with four combinations of inputs were developed to
      detect infected quarters. One input combination involved principal components
      (PC) adopted for addressing multi-collinearity in the data. The PC-based MLP
      model was superior to other non-PC-based models in terms of less complexity and
      higher predictive accuracy. The overall correct classification rate (CCR),
      sensitivity and specificity of this model were 90.74%, 86.90% and 91.36%,
      respectively. The SOM detected the stage of progression of mastitis in a quarter
      within the mastitis spectrum and revealed that quarters form three clusters:
      healthy, moderately ill and severely ill. The clusters were validated using k
      means clustering, ANOVA and least significant difference. Clusters reflected the
      characteristics of healthy and subclinical and clinical mastitis, respectively.
      We conclude that the PC based model based on EC and QY can be used in AMS to
      detect mastitis with high accuracy and that the SOM model can be used to monitor
      the health status of the herd for early intervention and possible treatment.

PMID- 20030901
TI  - Evaluation of different approaches for the estimation of daily yield from single
      milk testing scheme in cattle.
AB  - Three models for the estimation of milk, fat and protein daily yield (DY) based
      on a.m. (AM) or p.m. (PM) milkings were compared. A total of 518 766 test-day
      records from 5078 dairy cattle farms obtained between March 2004 and April 2008
      were analysed. The DY model was a linear model with DY as a dependent variable.
      In the PYR model and the DYR model, partial yield ratios (AM:DY and PM:DY) and
      daily yield ratios (DY:AM and DY:PM), respectively, were used as a dependent
      variable in the first step. In the second step, DY was estimated as a partial
      yield divided (PYR model) or multiplied (DYR model) by the estimated yield ratio
      from the first step. Models included the effect of partial yield (only in the DY
      model), milking interval, stage (month) of lactation and parity. Analysis of
      variance indicated that partial yield was the most important source of variation
      for the DY model whereas milking interval had the biggest effect in the PYR model
      and the DYR model. Differences in accuracy (correlation between the true and the
      estimated DY) between the models were negligible. On the other hand, models
      differed in the amount of bias (average error). The DYR model on average
      overestimated DY by 0.13 kg, 0.01 kg and 0.01 kg for milk, fat and protein,
      respectively. For the other two models the overall bias was almost zero. However,
      the DY model overestimated low and underestimated high DY owing to the well known
      regression property. The DYR model progressively overestimated high DY. These
      problems were not observed with the PYR model which seemed to be the best model.
      In this paper a relatively old topic was analysed and discussed from a new point
      of view, where the estimation of DY is based on modelling biologically more
      stable partial yield ratios rather than yield values from a.m. or p.m. milking.

PMID- 20030902
TI  - Relationship between virulence factor genes in bovine Staphylococcus aureus
      subclinical mastitis isolates and binding to anti-adhesin antibodies.
AB  - Staphylococcus aureus is the most common aetiologic agent of contagious bovine
      mastitis. It is characterized by a wide array of virulence factors. The
      differences among strains jeopardize the development of effective vaccines
      against Staph. aureus mastitis. We tested the immunogenicity of a peptide subunit
      vaccine coding for three different adhesion factors, fibrinogen-binding protein
      (Efb), fibronectin-binding protein A (FnbpA) and clumping factor A (ClfA). Then
      we evaluated the influence of some virulence factors on the ability of specific
      anti-adhesin antibodies to react with sixteen Staph. aureus strains isolated from
      bovine subclinical mastitis. Immunization with the recombinant adhesins
      stimulated a strong humoural (IgG and IgA) and mucosal IgA immune response in all
      animals tested. Hyperimmune serum recognized with diverse efficiency the sixteen
      Staph. aureus strains and this circumstance correlated well with the level of
      expression of adhesins. Among the different virulence factors considered to
      classify strains, spa gene polymorphisms showed the strongest influence on
      isolate reactions to hyperimmune serum. Our results indicate the importance of a
      disease- and environment-specific analysis of isolates. Thus, as opposed to other
      pathogens to obtain an effective vaccine we should characterize multiple strains
      and identify the prevalent virulence factors expressed.

PMID- 20030903
TI  - Milk production, peripartal liver triglyceride concentration and plasma
      metabolites of dairy cows fed diets supplemented with calcium soaps or
      hydrogenated triglycerides of palm oil.
AB  - The aim of the study was to test the effect of rumen-inert fat supplements of
      different chemical forms or containing different unsaturated/saturated (U/S)
      fatty acid contents on milk production, milk composition and liver and blood
      metabolic variables of high-yielding dairy cows in the peripartal period. Thirty
      Holstein-Friesian dairy cows were divided into three equal groups and fed a corn
      silage-based diet, without fat supplementation (control) or supplemented with
      11.75 MJ NEl per day of calcium soaps of palm oil fatty acids (CAS; U/S=61/39) or
      with 11.75 MJ NEl per day of hydrogenated palm oil triglyceride (HTG; U/S=6/94).
      Each diet was fed from 25+/-2 d prior to the expected calving to 100+/-5 d post
      partum. Compared with the control, both CAS and HTG supplementation resulted in
      an increase of the average milk yield. Milk fat content and fat-corrected milk
      yield were higher in the HTG group but lower in the CAS group than in the control
      group. In all groups liver triglyceride concentrations (TGL) increased from 15 d
      prepartum to 5 d post partum, and then decreased thereafter. At 5 d TGL was lower
      in the HTG group than control or CAS cows. No significant differences were
      detected in TGL among dietary treatments at 15 d prepartum and 25 d post partum.
      Higher plasma glucose and insulin and lower non-esterified fatty acids and beta
      hydroxybutyrate concentrations and aspartate aminotransferase activity were
      measured in the HTG group than in the control or CAS groups at 5 d or 25 d post
      partum. Our results show that HTG may provide a better energy supply for high
      yielding dairy cows in negative energy balance than CAS around calving.

PMID- 20030904
TI  - Effect of postprandial modulation of glucose availability: short- and long-term
      analysis.
AB  - Low glycaemic index (LGI) foods have been proposed as potential means to decrease
      postprandial glucose excursions and thus to improve diabetes management. We
      modulated glucose availability of cereal products and thus their glycaemic index
      to study the metabolic effect of LGI foods on daylong glucose control acutely and
      in the long term following a 5-week GI intervention diet in free-living subjects.
      In this randomised, parallel trial, two groups of nineteen overweight subjects
      followed an ad libitum 5-week intervention diet in which usual starch was
      replaced by either LGI or high GI (HGI) starch. During the exploration days (days
      1 and 36), subjects ate their assigned 13C-labelled test breakfast (LGI or HGI),
      and total and exogenous glucose kinetics (using stable isotopes), postprandial
      concentrations of glucose, insulin, lipid profile and nutrient oxidation were
      assessed after the test breakfast and a standardised lunch. At day 1, LGI
      breakfast significantly decreased post-breakfast glycaemic response with a
      parallel decrease in exogenous and total glucose appearance (P < 0.05). Post
      lunch and post-breakfast glycaemic responses were positively correlated (r 0.79,
      P < 0.0001). Following the 5-week diet, difference between the groups in terms of
      glucose kinetics and response was maintained (no significant interaction group x
      time) but tended to decrease over time for the post-breakfast glycaemic response.
      Post-lunch and post-breakfast glycaemic responses remained positively correlated
      (r 0.47, P = 0.004). Modulation of postprandial glucose availability at breakfast
      decreased plasma exogenous glucose appearance and improved glucose control at the
      subsequent lunch. After 5 weeks, these effects were maintained in healthy
      subjects but remained to be confirmed in the longer term.

PMID- 20030905
TI  - Bovine colostrum supplementation attenuates the decrease of salivary lysozyme and
      enhances the recovery of neutrophil function after prolonged exercise.
AB  - Oral supplementation with bovine colostrum (COL) has been shown to enhance
      immunity in human subjects. However, there is limited research on the use of
      bovine COL supplementation to counter exercise-induced immunodepression, as a
      model of stress-induced immunodepression, and previous research has focused
      primarily on salivary IgA. The aim of the present study was to determine the
      effects of bovine COL supplementation on exercise-induced changes in innate
      immunity (neutrophil function and salivary lysozyme) in addition to salivary IgA.
      Twenty healthy, active men cycled for 2 h at approximately 64 % maximal oxygen
      uptake after 4 weeks of daily bovine COL (n 10) or placebo (PLA, n 10)
      supplementation. Blood and saliva samples were obtained before and after
      supplementation, before and after exercise. Exercise induced significant
      increases in markers of physiological stress and stress to the immune system
      (circulating neutrophils, neutrophil:lymphocyte ratio, immature granulocytes,
      atypical lymphocytes and plasma cortisol), but there were no differences between
      the COL and PLA groups. Significant group x time interactions (two-way mixed
      model ANOVA) were observed for neutrophil function (stimulated degranulation) and
      salivary lysozyme concentration and release (P < 0.05). Significant exercise
      induced decreases were observed in these parameters, and bovine COL
      supplementation either speeded the recovery (neutrophil function) or prevented
      the decrease (salivary lysozyme) in these measures of innate immunity. These
      results suggest that 4 weeks of bovine COL supplementation limits the
      immunodepressive effects induced by an acute prolonged physical stressor, such as
      exercise, which may confer some benefits to host defence.

PMID- 20030906
TI  - Impact of adopting a vegan diet or an olestra supplementation on plasma
      organochlorine concentrations: results from two pilot studies.
AB  - The aim of these studies was to evaluate the potential of some nutritional
      approaches to prevent or reduce the body load of organochlorines (OC) in humans.
      Study 1 compared plasma OC concentrations between vegans and omnivores while
      study 2 verified if the dietary fat substitute olestra could prevent the increase
      in OC concentrations that is generally observed in response to a weight-reducing
      programme. In study 1, nine vegans and fifteen omnivores were recruited and the
      concentrations of twenty-six OC (beta-hexachlorocyclohexane (beta-HCH), p, p'
      dichlorodiphenyldichloroethane (p, p'-DDE), p, p'-dichlorodiphenyltrichloroethane
      (p, p'-DDT), hexachlorobenzene, mirex, aldrin, alpha-chlordane, gamma-chlordane,
      oxychlordane, cis-nonachlor, trans-nonachlor, polychlorinated biphenyl (PCB) nos.
      28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187, and aroclor
      1260) were determined. In study 2, the concentrations of these twenty-six OC were
      measured before and after weight loss over 3 months in thirty-seven obese men
      assigned to one of the following treatments: standard group (33 % fat diet; n
      13), fat-reduced group (25 % fat diet; n 14) or fat-substituted group (1/3 of
      dietary lipids substituted by olestra; n 10). In study 1, plasma concentrations
      of five OC compounds (aroclor 1260 and PCB 99, PCB 138, PCB 153 and PCB 180) were
      significantly lower in vegans compared with omnivores. In study 2, beta-HCH was
      the only OC which decreased in the fat-substituted group while increasing in the
      other two groups (P = 0.045). In conclusion, there was a trend toward lesser
      contamination in vegans than in omnivores, and olestra had a favourable influence
      on beta-HCH but did not prevent plasma hyperconcentration of the other OC during
      ongoing weight loss.

PMID- 20030907
TI  - A transmission electron microscope study on the route of entry of triclabendazole
      into the liver fluke, Fasciola hepatica.
AB  - Uptake of triclabendazole by the liver fluke, Fasciola hepatica has been studied
      by experiments designed to block either oral uptake of drug, by use of ligatures,
      or trans-tegumental diffusion, by allowing the drug to bind to an excess of
      bovine serum albumin (BSA) in the medium. Changes to the tegumental system,
      musculature and gut were assessed using transmission electron microscopy. Flukes
      were incubated in vitro for 24 h in TCBZ.SO (15 microg/ml). Disruption to the
      tegument and muscle was similar in ligatured and non-ligatured flukes, suggesting
      that closing the oral route did not affect drug uptake. The ultrastructure of the
      gastrodermal cells remained unchanged. Non-ligatured flukes were also incubated
      for 24 h in vitro in TCBZ.SO (15 microg/ml) in the presence of red blood cells
      (RBCs). Oral uptake of blood was demonstrated, but gut ultrastructure remained
      normal, whereas the tegument was severely disrupted. In separate experiments,
      ligatured and non-ligatured flukes were incubated in TCBZ.SO (15 microg/ml) in
      the presence of BSA (30 mg/ml) for 24 h in vitro. There was a marked decrease in
      the degree of tegumental disruption observed compared with TCBZ.SO action alone;
      again, the gut remained normal. The findings support previous morphological and
      pharmacological studies indicating that trans-tegumental uptake of
      triclabendazole predominates in the liver fluke.

PMID- 20030908
TI  - A layered structure in the organic envelopes of the prismatic layer of the shell
      of the pearl oyster Pinctada margaritifera (Mollusca, Bivalvia).
AB  - The organic interprismatic layers of the mollusc Pinctada margaritifera are
      studied using a variety of highly spatially-resolved techniques to establish
      their composition and structure. Our results show that both the interlamellar
      sheets of the nacre and interprismatic envelopes form layered structures.
      Additionally, these organic layers are neither homogeneous in composition, nor
      continuous in their structure. Both structures play a major role in the
      biomineralization process and act as a boundary between mineral units.

PMID- 20030909
TI  - Colloidal palladium particles of different shapes for electron microscopy
      labeling.
AB  - The immunogold technique is a valuable method for labeling cellular
      macromolecules. However, multiple labeling using colloidal gold (cAu)
      nanoparticles of different sizes presents certain drawbacks; namely, as particle
      size increases, there is a decreased labeling efficiency and diminished spatial
      resolution with respect to the locations of labeled epitopes. Both concerns also
      limit the utility of heavy metal particles for comparative analysis of labeling
      densities. To minimize the variables due to differential labeling efficiencies,
      the best solution would be to conduct multiple labeling with particles of similar
      size. Consequently, some parameter other than size is necessary to distinguish
      each label type. In this study, we report the synthesis of colloidal palladium
      (cPd) nanoparticles of similar size but having two distinct shapes, umbonate and
      faceted, which are readily distinguishable from spherical colloidal gold
      particles. Their utility and fidelity as labels using a human platelet whole
      mount model is also demonstrated.

PMID- 20030910
TI  - Fractal and image analysis of the microvasculature in normal intestinal submucosa
      and intestinal polyps in Apc(Min/+) mice.
AB  - Tumors are supported by the development of a unique vascular bed. We used fractal
      dimension (Db) and image analysis to quantify differences in the complexity of
      the vasculature in normal intestinal submucosa and intestinal polyps. Apc(Min/+)
      mice and wild-type mice were perfused with a curable latex compound, intestines
      sectioned, and images collected via confocal microscopy. The images were analyzed
      and area (A), perimeter (P), and integrated optical density (IOD) of the normal
      and tumor vascular beds were measured. The Db, a quantitative descriptor of
      morphological complexity, was significantly greater for the polyp vasculature
      from Apc(Min/+) mice than controls. This indicates that the polyp
      microvasculature is more chaotic than that of the controls, while the IOD and
      average vascular density values displayed no differences. This suggests the mass
      of blood volume is equivalent in normal and polyp microvasculature. The lower
      vascular area-perimeter ratios expressed by the polyp microvasculature suggest it
      is composed of smaller, more tortuous vessels. These data demonstrate that
      fractal analysis is applicable for providing a quantitative description of
      vascular complexity associated with angiogenesis occurring in normal or diseased
      tissue. Application of Db, IOD, and average density provides a clearer
      quantification of the complex morphology associated with tissue microvasculature.

PMID- 20030911
TI  - Electron-beam-induced carbon contamination on silicon: characterization using
      Raman spectroscopy and atomic force microscopy.
AB  - Electron-beam-induced carbon film deposition has long been recognized as a side
      effect of scanning electron microscopy. To characterize the nature of this type
      of contamination, silicon wafers were subjected to prolonged exposure to 15 kV
      electron beam energy with a probe current of 300 pA. Using Raman spectroscopy,
      the deposited coating was identified as an amorphous carbon film with an
      estimated crystallite size of 125 A. Using atomic force microscopy, the cross
      sectional profile of the coating was found to be raised and textured, indicative
      of the beam raster pattern. A map of the Raman intensity across the coating
      showed increased intensity along the edges and at the corner of the film. The
      intensity profile was in excess of that which could be explained by thickness
      alone. The enhancement was found to correspond with a modeled local field
      enhancement induced by the coating boundary and showed that the deposited carbon
      coating generated a localized disturbance in the opto-electrical properties of
      the substrate, which is compared and contrasted with Raman edge enhancement that
      is produced by surface structure in silicon.

PMID- 20030912
TI  - Electron probe microanalysis of thin films and multilayers using the computer
      program XFILM.
AB  - XFILM is a computer program for determining the thickness and composition of thin
      films on substrates and multilayers by electron probe microanalysis. In this
      study, we describe the X-ray emission model implemented in the latest version of
      XFILM and assess its reliability by comparing measured and calculated k-ratios
      from thin-film samples available in the literature. We present and discuss
      examples of applications of XFILM that illustrate the capabilities of the
      program.

PMID- 20030913
TI  - Characterization of SiGe films for use as a National Institute of Standards and
      Technology Microanalysis Reference Material (RM 8905).
AB  - Bulk silicon-germanium (SiGe) alloys and two SiGe thick films (4 and 5 microm) on
      Si wafers were tested with the electron probe microanalyzer (EPMA) using
      wavelength dispersive spectrometers (WDS) for heterogeneity and composition for
      use as reference materials needed by the microelectronics industry. One alloy
      with a nominal composition of Si0.86Ge0.14 and the two thick films with nominal
      compositions of Si0.90Ge0.10 and Si0.75Ge0.25 on Si, evaluated for micro- and
      macroheterogeneity, will make good microanalysis reference materials with an
      overall expanded heterogeneity uncertainty of 1.1% relative or less for Ge. The
      bulk Ge composition in the Si0.86Ge0.14 alloy was determined to be 30.228% mass
      fraction Ge with an expanded uncertainty of the mean of 0.195% mass fraction. The
      thick films were quantified with WDS-EPMA using both the Si0.86Ge0.14 alloy and
      element wafers as reference materials. The Ge concentration was determined to be
      22.80% mass fraction with an expanded uncertainty of the mean of 0.12% mass
      fraction for the Si0.90Ge0.10 wafer and 43.66% mass fraction for the Si0.75Ge0.25
      wafer with an expanded uncertainty of the mean of 0.25% mass fraction. The two
      thick SiGe films will be issued as National Institute of Standards and Technology
      Reference Materials (RM 8905).

PMID- 20030914
TI  - [A comparative cytogenetic analysis in large scale between adult and childhood
      patients with acute lymphoblastic leukemia].
AB  - This study was purposed to comparatively analyze the cytogenetic characteristics
      between 566 cases of adult acute lymphoblastic leukemia (aALL) and 586 cases of
      childhood acute lymphoblastic leukemia (cALL). The cytogenetic analysis of all
      the patients was performed, and the FISH detection for partial patients was
      carried out. The result showed that the difference of chromosome abnormality
      between cALL and aALL was statistically significant. The percentage of abnormal
      karyotypes in aALL was 62.0%, including mainly t(9;22)(q34;q11), hypodiploidy,
      hyperdiploidy (47 - 50), abn(6q), abn(9p) and -7, most of which conferring an
      unfavorable prognosis. The percentage of abnormal karyotypes in cALL was 39.2%,
      composed mainly of high hyperdiploidy, hypodiploidy, TEL/AML1(+), +8,
      hyperdiploidy (47 - 50) and +21, etc, most of which conferring a favorable
      prognosis. The incidences of abnormal karyotypes, total hypodiploidy, total
      hyperdiploidy (47 - 50), t(9;22)(q34;q11), -7, abn(7q), abn(14q32) and +Ph in
      aALL were significantly higher than those of cALL (p < 0.05), whereas the
      incidences of normal karyotype (N), high hyperdiploidy, +8, +21*2 and TEL/AML1(+)
      in cALL were significantly higher than those of aALL (p < 0.05). 20.5% of aALL
      were Ph+ aALL, with 63.8% of which being with additional abnormalities, composed
      mainly of +Ph, -7, i (9q+), 9p-, +8, +21, +X, 6q-, abn(14q32) and +14. In
      contrast, only 4.4% of cALL were Ph+ aALL, with 42.3% of which being with
      additional abnormalities, including mainly abn(9p), abn(7p), -7, 17p- and +21. It
      is concluded that almost every chromosome is involved in the numerical and
      structural abnormalities and complex karyotypes are common. The significant
      difference of chromosome abnormality exists between aALL and cALL.

PMID- 20030915
TI  - [Methylation status of JunB and CDH13 gene promoter in CD34(+)CD38(-) chronic
      myelogenous leukemia cells].
AB  - Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease of
      transformed hematopoietic progenitor cells. The expressions of JunB and CDH13
      (cadherin-13) gene as tumor suppressor gene were inactivated by promoter
      methylation in CML patients. This study was purposed to investigate the
      methylation difference of JunB and CDH13 gene promoter and the expression levels
      of JunB and CDH13 gene in CD34(+)CD38(-) cells in CML patients vs normal
      individuals. CD34(+)CD38(-) cells from 8 cases of CML and 5 normal individuals
      were selected by flow cytometry. The methylation status of JunB and CDH13 genes
      were detected by MS-PCR in selected CD34(+)CD38(-) cells. The expression levels
      of JunB and CDH13 gene was detected with real time polymerase chain reaction (RT
      PCR). The results showed that no methylation of JunB and CDH13 gene was detected
      in CD34(+)CD38(-) cells of 5 normal individuals. Methylations of JunB and CDH13
      promoter were found in 87.5% (7/8) and 50% (4/8) CML CD34(+)CD38(-) cells,
      percentages of which were significantly higher than those in normal individuals.
      The difference was statistically significant (p < 0.05). The relative expression
      levels of JunB and CDH13 mRNA in CD34(+)CD38(-) cells of CML patients were
      significantly lower than those in normal individuals (2(-DeltaDeltaCT) were
      1/5.21 and 1/10.63 respectively). It is concluded that the high methylation of
      JunB and CDH13 gene promoter occurs in CD34(+)CD38(-) cells of CML patients,
      their mRNA expression level is significantly lower, thus the methylation of JunB
      and CDH13 gene promoter probably plays a role in the pathogenesis of CML and may
      have clinical significance in predicting prognosis of CML.

PMID- 20030916
TI  - [Telomere length and telomerase expression activity in mononuclear cells of
      patients with chronic lymphocytic leukemia].
AB  - This study was aimed to detect the telomere length and the telomerase expression
      activity in patients with chronic lymphocytic leukemia (CLL), and investigate
      their relation to prognosis of CLL. The telomere length and the telomerase
      expression activity of peripheral blood and / or bone marrow mononuclear cells
      were examined by Tel-FISH, a semi-quantitative method and by TRAP-ELISA
      respectively; the expressions of ZAP70 and CD38 were detected by flow cytometry.
      The results showed that comparing the telomere length in different stages, there
      was a tendency that the telomere became prolonged when the stage raised up. There
      was statistical significant difference between Rai stages III-IV and stage 0, Rai
      stages III-IV and stages I-II, Binet stage C and stage A, Binet stage C and stage
      B; while no statistical significant difference existed between Rai stage 0 and
      stages I-II, Binet stage A and stage B. The telomere length in ZAP70 negative
      group was found similar as in ZAP70 positive group. The telomere length in CD38
      positive group was shorter than that in CD38 negative group, but there was no
      statistical difference between them. Comparing the telomerase expression activity
      between different stages, there was a tendency that it increased when the stages
      went up; comparing the telomerase expression activity at different Rai stages, it
      increased at the higher stages. One case of CLL demonstrated that telomerase
      expression did not show at remission stage, but was found at relapse stage, which
      suggested that telomerase expression may relate to prognosis of disease. It is
      concluded that the telomerase length is in relation to Rai and Binet stage, which
      was shorter at higher stage than that at lower stage and intermediate stage. It
      seemed that the telomerase expression activity increased at higher stages. The
      expression of telomerase in mononuclear cells is stable and not influenced by
      treatment.

PMID- 20030917
TI  - [Inhibition effect of short hairpin RNA on VEGF receptor flt-1 gene expression in
      leukemia cell line K562].
AB  - This study was purposed to investigate the inhibitory effect of short hairpin RNA
      (shRNA) on expression of vascular endothelial growth factor (VEGF) receptor flt-1
      gene in leukemia cells line K562, and to explore the influence of shRNA invasive
      ability on leukemia cells and its mechanism. The recombinant eukaryotic
      expression plasmid containing flt-1 shRNA gene was transfected into K562 cells by
      lipofectamine mediation and positive clones were screened by G418. shRNA gene in
      K562 cells was confirmed by PCR. RT-PCR and Western blot were employed to detect
      the expression of flt-1 mRNA and protein in leukemia cells. The invasive ability
      of K562 cells was studied by Boyden chamber invasion assay before and after flt-1
      shRNA transfection. MMP-2 and MMP-9 mRNA expressions were detected by RT-PCR
      after transfection of the recombinant plasmid C1/U6/FltS2 into K562 cells through
      liposome. The results showed that the recombinant eukaryotic expression plasmid
      had been transfected into the human leukemia cell line K562 and positive clones
      had been screened by G418 for 2 weeks. PCR detection revealed the stable
      expression of the shRNA gene in K562 cells. Flt-1 gene and protein expressions
      were inhibited by plasmid-expressed shRNA after transfection of recombinant
      vetors C1/U6/FltS into K562 cells. The inhibitory efficiency of two different
      shRNA sequences targeting Flt-1 gene were 46.1% and 65.4% respectively. The
      expression of MMP-2 and MMP-9 mRNA decreased, and the mean invasion rate in
      C1/U6/fltS2-transfected K562 cells was lower than that in nontransfected cells.
      It is concluded that shRNA eukaryotic expression vector specific to VEGF receptor
      flt-1 gene can high efficiently be transfected into leukemia cell line K562,
      effectively inhibits the expression of flt-1 gene, weakens the in vitro invasive
      ability of leukemia cells and the expression levels of MMP-2 and MMP-9 mRNA,
      which suggests that the VEGF involves in the migration of leukemia cells by
      regulating the MMP-2 and MMP-9 through joints with the receptor.

PMID- 20030918
TI  - Cross-lineage expression in 505 patients with acute lymphoblastic leukemia by
      multiparametric flow cytometry analysis.
AB  - The expression of immunological markers of one hematopoietic lineage on the
      abnormal cells of another lineage (cross-lineage expression) is a known feature
      of leukemia. The present study was aimed to investigate the cross-lineage
      expression in ALL cells. The cross-lineage expression in ALL cells from 505
      patients was detected by flow cytometry using 23 monoclonal antibodies (McAbs) in
      triple staining combinations. The results showed that in whole ALL, the
      expression of myeloid antigens occurred in 56.4% of the cases, and CD13 was the
      most frequently expressed myeloid marker (32.7%) followed by CD33 (29.5%), CD15
      (19.2%) and CD11b (7.7%). CD13/CD33 expressions were more frequent in CD34(+)
      cases than in CD34(-) cases. In B-ALL, T-cell antigen CD4, CD5, CD7 and CD2 were
      found in 27 (6.3%), 12 (2.8%), 8 (1.9%), and 6 (1.4%) cases respectively, and
      CD7(+), CD2(+) and CD4(+) cases commonly expressed CD13/CD33. In T-ALL, B-cell
      antigen cCD79a, CD19 and CD22 were found in 6 (8.1%), 5 (6.8%), and 2 (2.8%)
      cases respectively, and all of CD19(+) and CD22(+) cases were all accompanied
      with CD13/CD33. It is concluded that cross-lineage expression in ALL mostly
      exists in the immature stages, ALL cells more frequently express phenotypes
      B(+)M(+), T(+)M(+) and occasionally B(+)T(+)M(+), but B(+)T(+)M(-) phenotype is
      extremely rare.

PMID- 20030919
TI  - [Expression of antiapoptotic gene aven in de novo acute myeloid leukemia patients
      and its clinical significance].
AB  - This study was aimed to investigate the aven mRNA expression level of leukocytes
      from peripheral blood(PB)of de novo patients with acute myeloid leukemia (AML)
      and analyze its clinical significance, so as to provide a experimental basis for
      evaluating prognosis. The aven mRNA expression levels in PB samples from 69 de
      novo AML patients were detected by using real-time quantitative PCR. The relation
      of aven mRNA level with clinical and hematological characteristics (age, sex,
      WBC, Hb, Plt, LDH, Blast% in PB and BM, FAB subtype) and treatment outcome (CR
      rate and relapse rate) were analyzed. 21 normal individuals served as controls.
      The results showed that the expression level of aven mRNA was between 11.72% and
      178.93% (median 37.2%) in de novo AML and between 10.81% and 50.98% (median
      28.81%) in normal individuals. Aven mRNA expression level was higher in the AML
      group than that in the controls (p = 0.006). As aven mRNA expression level was
      compared with other clinical and hematological parameters, there were significant
      correlations between aven mRNA expression level and age (r = 0.25, p = 0.039),
      and between hemoglobin level (r = 0.29, p = 0.019), FAB subtype(r = 0.253, p =
      0.036). The median expression level (50.08%) of aven mRNA in older patients (> or
      = 44 years) was higher then that (32.41%) in younger patients (< 44 years) (p =
      0.018). The complete remission (CR) rate after two cycles of chemotherapy in
      patients with lower aven mRNA level (25/30, 83.33%) was higher than that in
      patients with higher aven mRNA level(21/30, 70%), but the difference was not
      significant(p = 0.22). The difference of aven mRNA expression level between AML
      patients with relapse and AML patents without relapse was not significant (p =
      0.076). It is concluded that the expression level of aven mRNA in de novo AML
      patients obviously increases, the overexpression of aven mRNA likely involves in
      genesis of AML. The definite relation of aven mRNA expression level with
      treatment outcome and relapse was not been found.

PMID- 20030920
TI  - [Expression of c-fes gene in leukemia cells and its clinical significance].
AB  - This study was purposed to investigate the expression of c-fes gene in leukemia
      patients and its clinical significance. The expression of c-fes mRNA in bone
      marrow cells from 121 cases of acute and chronic leukemia patients, and the
      expression of c-fes mRNA in peripheral blood mononuclear cells of 20 normal
      persons were detected by real time-quantitative reverse transcription polymerase
      chain reaction (RQ-PCR). The results showed that the level of c-fes mRNA in AML
      patients was higher than that in normal controls [(48.017 +/- 57.170) x 10(-3) vs
      (0.152 +/- 0.398) x 10(-3)] (p < 0.0001); but there was no significant
      differences of level of c-fes mRNA between samples of ALL and normal
      controls(0.047 +/- 0.068) x 10(-3) vs(0.152 +/- 0.398) x 10(-3) (p>0.05); the
      level of c-fes mRNA in CML patients was higher than that in normal persons
      (21.605 +/- 24.818) x 10(-3) vs (0.152 +/- 0.398) x 10(-3) (p < 0.0001). The
      positive expression rate of c-fes gene in CML-CP patients (80%) was higher than
      that in CML-AP patients (66.7%) and CML-BP (28.6%) patients. In AML patients, c
      fes gene was expressed higher in M(2) (80.77%) and M(3) (92.86%) patients. The
      remission rate of AML (except M(3))patients who had expression of c-fes gene was
      81.08%, which was higher than that of patients with no expression of c-fes gene
      (40.00%). It is concluded that c-fes gene expression was found in myeloid
      leukemias, whereas low or no expression in lymphocytic leukemias. The
      differentiation of myelocytic cells may be related to c-fes gene. All AML (except
      M(3))patients with high level of c-fes mRNA may get good prognosis.

PMID- 20030921
TI  - [Effect of emodin on proliferation inhibition and apoptosis induction in leukemic
      K562 cells].
AB  - The study was aimed to investigate the effects of emodin on proliferation
      inhibition and apoptosis induction in human chronic myeloid leukemia cell line
      K562 cells, and to explore the role of P210 protein and activation of caspase 3
      in these processes. K562 cells were exposed to emodin at different doses. The
      proliferation inhibition was detected by MTT assay and colony formation test. The
      ability of emodin to induce apoptosis and DNA fragmentation were examined by flow
      cytometry. The expressions of P210, procaspase-3 and PARP protein were determined
      by Western blot. The results indicated that the emodin remarkably inhibited the
      K562 cell proliferation, with IC(50) value of 38.25 micromol/L after treatment
      for 48 hours. Meanwhile induced apoptosis, Annexin V-FITC positive cells, sub
      G(1) apoptotic peak and DNA fragmentation in K562 cells confirmed that emodin
      induced apoptosis in K562 cells in dose-dependent manner. Western blot results
      showed that emodin inhibited phosphorylation of P210 protein in K562 cells and
      down-regulated the expression levels of P210. The procaspase-3 level in treated
      K562 cells decreased with increased expressions of PARP in time-dependent manner.
      It is concluded that the emodin efficiently inhibits growth and induces apoptosis
      of K562 cells, while the inhibition of phosphorylation of P210 protein, down
      regulation of P210 protein expression and activation of caspase-3 may be involved
      in these processes.

PMID- 20030922
TI  - [Effect of compound Zhe-Bei granule (CZBG) combined with doxorubicin on cell
      apoptosis and expression of related proteins in K562/A02 multidrug resistance
      tumor xenografts in mice].
AB  - This study was purposed to investigate the effects of compound Zhe-Bei granule
      (CZBG) combined with doxorubicin (Dox) on the expression of BCL-2, BAX and cell
      apoptosis rate in K562/A02 multidrug resistant tumor xenografts. Tumor xenograft
      model was established by injecting the K562/A02 cells into the axillary flank of
      BALB/c nude mice. The cell apoptosis rate of xenografts was detected by flow
      cytometry with Annexin V-FITC/PI staining. The expressions of BCL-2 and BAX in
      xenografts were measured by immunohistochemistry staining. The value of integral
      optical density (IOD) was calculated according to staining image on slide. The
      results indicated that as compared with normal saline control group and Dox
      group, the high, middle, low dose of CZBG combined with Dox could increase the
      cell apoptosis rate of tumor xenografts with statistical significance (p < 0.05);
      and could decrease the IOD value of BCL-2 and increase the IOD value of BAX in
      xenografts with statistical significance (p < 0.05). It is concluded that CZBG
      combined with Dox can enhance the apoptosis rate in K562/A02 cells, down-regulate
      the expression of BCL-2 and up-regulate the expression of BAX, thereby, can
      reverse the multidrug resistance of K562/A02 cells by decreasing the ratio of BCL
      2/BAX.

PMID- 20030923
TI  - [Apoptosis-inducing effect of gambogic acid on K562 cells and its mechanism].
AB  - This study was aimed to investigate the apoptosis-inducing effect of gambogic
      acid (GA) on K562 cell line and its mechanism. The K562 cells were treated with
      GA at different concentrations and times, the inhibition rates were detected by
      MTT assay. Apoptosis induced by GA was assayed by Annexin-V/PI doubling staining.
      The influence of GA on cell cycle was studied by propidium iodide method. The
      mitochondrial membrane potential was measured by JC assay. The levels of caspase
      3, caspase 8 and caspase 9 activated by fluorescein in living K562 cells were
      measured by caspGLOW(TM) fluorescein staining kit. The results showed that after
      incubation with GA, K562 cell proliferation was dramatically inhibited in
      concentration- and time-dependent manners. K562/A02 cells need higher GA
      concentration (> 2 microg/ml) to show antiproliferative effect, compared with
      that of K562 cells (> 0.5 microg/ml). Apoptosis could be induced by GA but the
      influence on cell cycle was not significant. GA could decrease the mitochondrial
      membrane potential and increase the activated caspase 3, caspase 8, caspase 9
      positive cell levels by 2.19%, -1.95%, 34.01% in 24 hr and 60.4%, 71.3%, 77.7% in
      48 hr respectively. It is concluded that the GA can significantly inhibit the
      proliferation of K562 cells without influence on cell cycles. The GA triggers
      K562 cell apoptosis through both intrinsic and extrinsic pathways.

PMID- 20030924
TI  - [Pathological features and ultrastructure of N-methyl-N-nitrosourea (MNU)-induced
      thymic lymphomas in mice].
AB  - The objective of study was to investigate the origin and to classify the subtype
      of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice.
      Histopathologic, immunohistochemical and ultrastructural studies were performed
      to analyze the pathological features of the neoplasms. The results showed that
      the thymus in all cases became totally replaced by sheets of cells of the
      lymphoid series. All the tumors coexpressed CD3 and TdT. Transmission electron
      microscopic study showed the plasma membranes of malignant lymphoma cells were
      smooth. The nuclear profiles were usually regular, with varying percentage of
      convoluted nuclei. Few cell organoids were observed in cytoplasm. In conclusion,
      all the MNU-induced tumor classified by histopathologic, immunohistochemical and
      ultrastructural studies as precursor lymphoblastic lymphoma that were
      unquestionably related to the thymus origin and T-cell lineage.

PMID- 20030925
TI  - [Construction of expression plasmid for fused idiotypic DNA vaccine of B-cell
      lymphoma].
AB  - The idiotypic determinant of surface immunoglobulin of B-cell lymphoma, as a
      tumor-specific antigen, has proved to be able to induce immune responses. To
      analyze whether an idiotypic vaccine fused with cytokine can elicit more
      effectively protective antitumor immunity, an eukaryotic expression plasmid was
      constructed, which encoded the fusion gene of single-chain variable fragment as a
      tumor specific antigen against B-cell lymphoma with monocyte chemotactic protein
      3 (MCP3) as immunogen to elicit T-cell-dependent protective antitumor immunity,
      and EGFP (Enhanced Green Fluorescent Protein) gene as a marker to trace the
      survival, growth, differentiation and expression of the former exogenetic genes.
      The cDNAs for immunoglobulin (Ig) VH and IgVL were amplified by RT-PCR and
      assembled into the single-chain variable fragment (scFv) connected with a
      (Gly(4)Ser)(3) linker by recombinant PCR method. Then, the fragments of scFv and
      MCP3 were ligated with a NDAQAPKS spacer by the same method. The results showed
      that the fusion genes of scFv and MCP3-scFv were inserted into an eukaryotic
      expression vector pTARGET, and EGFP was cloned into the downstream of scFv and
      MCP3-scFv respectively. Finally the constructed plasmids were confirmed by
      sequencing and restriction analysis. In conclusion, a tumor-derived idiotypic DNA
      vaccine, encoding the fusion gene of single-chain variable fragment and monocyte
      chemotactic protein-3 (MCP3) to elicit a T-cell dependent, antitumor immunity,
      and the EGFP gene was inserted correctly. The DNA vaccine could be used for
      further study of DNA vaccine against B cell lymphoma in vivo.

PMID- 20030926
TI  - [Apoptosis of multiple myeloma cells induced by gossypol acetic acid in vitro and
      its mechanism].
AB  - This study was aimed to investigate the apoptosis effect of gossypol acetic acid
      on classic human multiple myeloma RPMI8226 cell line in vitro and its mechanism.
      The inhibitory effect on proliferation of RPMI8226 cells was evaluated by means
      of MTT assay. Cytotoxic effect and apoptosis was identified and analyzed with the
      aid of transmission electron microscopy, mitochondria membrane potential (MMP)
      and DNA gel electrophoresis. Meanwhile, Western-blot assay was used to detect the
      changes of several key cell apoptosis regulatory proteins such as BAX, caspase-3
      and caspase-8 in these cells before and after treatment. The results showed that
      low concentrations of gossypol acetic acid (> 16 micromol/L) could suppress the
      proliferation and induce the apoptosis in RPMI8226 cells effectively. At the same
      time, gossypol acetic acid could also down-regulate the mitochondrial membrane
      potential, up-regulate the expression of the apoptosis-related protein such as
      BAX and caspase-3. It is concluded that the gossypol acetic acid can selectively
      induce proliferation inhibition and apoptosis of multiple myeloma RPMI8226 cells
      with a smaller dose.

PMID- 20030927
TI  - [Expression of midkine and vascular endothelial growth factor in bone marrow of
      patients with multiple myeloma and its significance].
AB  - The purpose of this study was to explore the expressions of midkine (MK) and
      vascular endothelial growth factor (VEGF) in multiple myeloma (MM), and to
      evaluate their relation with angiogenesis and prognosis. The expression levels of
      MK and VEGF in bone marrow mononuclear cells of 31 MM patients in different
      stages and 20 controls were detected by real-time fluorescent quantitative RT
      PCR. The results showed that the MM patients had significantly higher MK and VEGF
      expression level than control group (p < 0.05, p < 0.01), and there was a linear
      relationship between MK and VEGF (r = 0.692, p < 0.01); The expression levels of
      MK and VEGF in stage III was significantly higher than those in stage I and stage
      II (p < 0.05, p < 0.01), but there was no difference between stage I and stage II
      (p > 0.05); MK and VEGF levels were significantly decreased in MM patients after
      treatment than those before treatment (p < 0.05, p < 0.01). It is concluded that
      the high expression of MK and VEGF is correlated with angiogenesis and prognosis
      of MM, and there is synergistic effect between MK and VEGF. It is supposed that
      the monitoring MK and VEGF expression levels may contribute to guide the
      treatment and estimate prognosis for MM.

PMID- 20030928
TI  - Combined effects of bortezomib and daunorubicin on multiple myeloma cell KM3 in
      vitro.
AB  - The aim of this study was to investigate the combined effects of bortezomib (Bor)
      and daunorubicin (DNR) or each drug alone on proliferation of human multiple
      myeloma cell line KM3. KM3 cells were cultured with different concentrations of
      Bor and DNR, Bor or DNR alone for different times. The cell proliferation was
      analyzed by MTT assay, and the concentration of 50% growth inhibition (IC(50))
      was calculated. The results indicated that both of Bor and DNR inhibited KM3 cell
      proliferation in dose dependent manner. The IC(50) of both drugs were 0.27
      micromol/L and 0.16 micromol/L respectively. The inhibiting rate of Bor plus DNR
      on KM3 cells was much higher than that of Bor (p < 0.05). It is concluded that
      the Bor has synergistic inhibitory effect with DNR on the growth of KM3 cell in
      vitro.

PMID- 20030929
TI  - [Analysis on laboratory and clinical characteristics in 65 cases of
      myelodysplastic syndrome].
AB  - The aim of this study was to gain more insight into the understanding of
      myelodysplastic syndrome in the clinical and laboratory features. The clinical
      data of 65 patients with MDS were reviewed and analysed. According to FAB
      criteria, 65 patients were classified as follows: 27 patients with RA, 1 patient
      with RAS, 33 patients with RAEB, 3 patients with RAEB-T, and 1 patient with CMML.
      The median age of them was 66 years old (range 19-89 years), and 6 patients had a
      history of toxic exposure (secondary MDS). The bone marrow smears, bone marrow
      biopsy and cytogenetic examinations were performed in this study. The results
      showed that dysplasia was found in 64 patients examined with bone marrow smears
      (98.5%), among them trilineage dysplasia in 21 patients (32.3%), bilineage
      dysplasia in 33 patients (50.8%), only erythroid dysplasia in 8 cases (12.3%) and
      2 patients (3.1%) only with myeloid dysplasia. The bone marrow biopsy was
      performed in 38 patients, abnormal localization of immature precursor (ALIP)
      occurred in 6 cases. 29 patients had abnormal karyotypes, accounting for 59.2% of
      the 49 patients subjected cytogenetic examination. The abnormal chromosome was
      the major cytogenetic abnormality, which occurred more often in secondary MDS and
      the patients with RAEB or RAEB-T. Among the 49 patients who had received
      cytogenetic examination, 15 patients transformed into AML with the incidence of
      30.61%, but only 3 out of 20 patients in the group of normal chromosome
      transformed into AML (15%), while 12 out of 29 patients in the group of abnormal
      karyotypes transformed into AML (41.4%). The median time of following up was 35
      months (range 2 - 106 months). The median survival time was 26.8 months and 8
      months in the patients with normal karyotype and chromosome aberrations
      respectively. In conclusion, the incidence of MDS in our country is younger than
      that in Western countries, the rate of abnormal chromosome in high risk MDS is
      higher than that in low risk MDS. Meanwhile, those who have the change of
      chromosome are related to the transformation of MDS into AML and have shorter
      survival time than those MDS patients with normal karyotypes.

PMID- 20030930
TI  - [Diagnostic significance of immunophenotyping of bone marrow cells in
      myelodysplastic syndrome without an increase of marrow blasts].
AB  - This study was aimed to investigate the characteristics of immunophenotypes in
      the patients with myelodysplastic syndrome (MDS) without an increase of marrow
      blasts, and to confirm their diagnostic significance. Marrow cells from 222
      patients with pancytopenia, dysplastic changes in one or more hematopoietic
      lineages and blast cells less than 5% were analyzed by multiparametric flow
      cytometry(FCM). The abnormal immunophenotypes were evaluated in asynchronous
      antigen expression (CD34 or CD117 in mature granulocytes or mature monocytes, HLA
      DR in mature granulocytes), in cross-lineage antigen expression (CD7 or CD56 in
      granulocytes or monocytes), in aberrant light-scatter (CD45/SSC in mature
      granulocyte or monocyte) and in abnormal expression of differentiation antigen
      (CD13/CD16 pattern in granulocytes and HLA-DR under-expression in monocytes). The
      sensitivity and specificity of abnormal immunophenotypes were determined on
      diagnosis. Among 222 cases, 127 cases were diagnosed as MDS by traditional
      diagnostic method and 95 cases were non-MDS (drug-related neutropenia, autoimmune
      cytopenia and idiopathic thrombocytopenia). In mature granulocyte gate, the
      sensitivity of asynchronous, cross-lineage antigen expression, aberrant light
      scatter of CD45/SSC and abnormal expression of differentiation antigen were
      31.5%, 30.7%, 49.6% and 60.6% respectively, and the specificity were 100%, 100%,
      88.4% and 52.6% respectively. In monocyte gate, the sensitivity of asynchronous,
      cross-lineage antigen expression, aberrant light-scatter of CD45/SSC and abnormal
      expression of differentiation antigen were 2.3%, 11%, 37% and 12.6% respectively.
      The specificity was 100% in all of them. Among 8 above mentioned items,
      sensitivity of more than 2 abnormalities was 77.9%, and specificity was 95.8%.
      The positive predictive value was 96.1%. It is concluded that the abnormal
      expression of asynchronous, cross-lineage antigen expression, aberrant light
      scatter of CD45/SSC have a high specificity and a low sensitivity for diagnosis
      of MDS. The abnormal expressions of differentiation antigens have a high
      sensitivity and a low specificity; however, the detection of multiple expression
      abnormalities possesses the high sensitivity and specificity for diagnosis of
      MDS.

PMID- 20030931
TI  - [Influence of AML1 and AML1-ETO on transcriptional regulation of nucb2 gene].
AB  - This study was purposed to investigate the effect of AML1-ETO fusion protein
      resulted from hematopoietic transcription factor (AML1) and acute myeloid
      leukemia M(2b)(AML-M(2b)) on transcription activity of nucleobindin 2 (nucb2)
      promoter, and to explore the role of AML1-ETO in molecular pathogenesis of AML
      M(2b). The real-time RT-PCR was used to study the regulation of AML1-ETO on nucb2
      at transcription level in AML1-ETO inducible leukemia cell line, the chromatin
      immunoprecipitation (ChIP)-based qPCR was used to investigate the direct in vivo
      interaction between the AML1, AML1-ETO and nucb2 promoter in AML1-ETO positive
      leukemia cell line, the luciferase report gene assay was used to detect the
      regulation of AML1, AML1-ETO on the transcription activity of nucb2 promoter. The
      results showed that the expression level of nucb2 was reduced with the increase
      of AML1-ETO. The promoter of nucb2 could be bound by both AML1 and AML1-ETO. The
      promoter of nucb2 was trans-repressed by AML1 and AML1-ETO respectively. It is
      concluded that the nucb2 is the direct target gene of AML1 and AML1-ETO, the
      transcription regulation of AML1, AML1-ETO on nucb2 is carried out via repressing
      its promoter activity.

PMID- 20030932
TI  - [Methylation status of CpG islands in secreted frizzled-related protein gene
      promoter region of malignant hematopoietic cell lines].
AB  - To investigate the methylation status of CpG islands of the secreted frizzled
      related protein (SFRP) gene promoter region in malignant hematopoietic cell
      lines, and to explore the possible relationship of CpG abnormal methylation
      status with pathogenic mechanism of hematologic malignancies. Methylation
      specific PCR was used to detect the status of SFRP gene promoter region in nine
      malignant hematopoietic cell lines and peripheral blood mononuclear cells from
      healthy people. The results indicated that hypermethylation of 2 genes coding for
      SFRP1 and 2 were present in nine malignant hematopoietic cell lines, however,
      methylation and unmethylation of SFRP4 were both detected in CA46, HL60 and U937
      cell lines, and SFRP5 in U266 as well. None of the normal mononuclear cells
      showed methylation of SFRP 1-5 genes. It is concluded that the hypermethylation
      of SFRP genes is related to the evolution of malignant hematopoiesis. Methylation
      of SFRP genes may serve as potential independent biomarkers for early detection
      of hematologic malignancies.

PMID- 20030933
TI  - [Immune regulation effect of rat dendritic cells phagocytosing photochemotherapy
      treated allogeneic cells on syngeneic T cells].
AB  - The aim of this study was to investigate the immune regulatory effect of
      dendritic cells phagocytosing photochemotherapy-treated allogeneic spleen
      lymphocytes on syngeneic T cells. DA rat spleen lymphocytes were treated with 8
      methoxypsoralen plus UVA irradiation (PUVA). LEW rat bone marrow-derived DCs were
      co-cultured with PUVA-treated DA spleen lymphocytes (PUVA-SP), and the surface
      markers (MHC-II, CD86 and CD40) of treated DC were detected by flow cytometry.
      CFSE-labeled PUVA SP were incubated with LEW DCs and the phagocytosis of DCs on
      PUVA-SP was observed by using fluorescent microscope. The ability of DC
      phagocytosing allogeneic PUVA-SP (PUVA-SP DC) to stimulate the proliferation of
      LEW T cells was analyzed by mixed leukocyte reactions (MLR). The production of IL
      4, IL-10, IL-2, IFN-gamma in MLR culture supernatant was determined by luminex
      method. The results indicated that the PUVA treatment effectively induced early
      apoptosis of DA rat spleen lymphocytes. After co-culture, DC efficiently
      phagocytosed allogeneic PUVA-SP and still maintained an immature phenotype with
      low levels of MHC II, CD40 and CD86. PUVA-SP DC induced LEW T cell
      hyporesponsiveness to DA rat antigen, and led to skewing of T cell cytokine
      expression toward Th2 (IL-10 and IL-4). It is concluded that the PUVA-SP DC
      effectively down-regulate T cell response to alloantigen and induce Th2 immune
      deviation in vitro.

PMID- 20030934
TI  - [Application of measuring human peripheral NK cell activity with flow cytometry
      in diagnosis for hemophagocytic lymphohistiocytosis].
AB  - The aim of study was to establish an accurate and stable technique for the
      detection of NK cell activity in the diagnosis of hemophagocytic
      lymphohistiocytosis (HLH). 21 suspected acquired HLH patients and 20 healthy
      subjects as controls were enrolled in the study, and the suspected HLH patients
      were divided into confirmedly diagnosed group and excluded group according to HLH
      2004 diagnostic criteria. The plasmid pEGFP-N1 was transfected into K562 cells.
      After scanned with G4l8 and monoclone, the EGFP-K562 cell line stably expressing
      enhanced green fluorescent protein was obtained. PBMNC and EGFP-K562 were mixed
      at the effector to target ratio of 10:1. After incubation for of 2 hours,
      propidium iodine (PI) was added to stain dead cells, and then cytotoxic activity
      was analyzed by using flow cytometry. Meanwhile, the cytotoxic activity of NK
      cells in peripheral blood on K562 cells was detected by LDH release assay, and
      was compared with results detected by flow cytometry. The results showed that a
      K562 cell line stably expressing EGFP was constructed and were used to measure NK
      cytotoxicity against the target cells by flow cytometry without pre-staining or
      pre-labeling target cells. There was significant difference in killing rate of NK
      cells between the diagnostic group and the control group. This new technique
      correlated strongly with the results by LDH release assay. In conclusion, this
      study provides a novel, simple, rapid, repeatable and reproducible method to
      measure NK activity by flow cytometry using EGFP-K562 without pre-staining or pre
      labeling target cells. It may be widely used in the diagnosis of hemophagocytic
      lymphohistiocytosis.

PMID- 20030935
TI  - [Relationship between midkine expression and drug efflux in childhood acute
      lymphoblastic leukemia cells].
AB  - This study was aimed to investigate the expression of midkine gene in childhood
      acute lymphoblastic leukemia patients (ALL) and to explore the possible effects
      of midkine gene on the chemotherapeutic drug efflux. Real-time quantitative PCR
      (RQ-PCR) method was used to determine the expression of midkine at mRNA level in
      153 ALL patients and 20 normal children. Meanwhile, laser scanning confocal
      microscope was used to observe the rhodamine 123 efflux from the mononuclear
      cells in 30 de novo B-ALL patients and 20 healthy individuals (as control). Flow
      cytometry was used to detect intracellular mean fluorescence intensity (MFI)
      which can reflect the degree of drug accumulation. The results showed that the
      significant statistical difference of midkine gene expression was found among the
      normal controls, the B-ALL patients in complete remission (CR) and progress with
      the expression level increasing in turns 0.795 (0.697 - 1.570), 3.012 (0.932 -
      5.076) and 12.909 (2.385 - 26.347) respectively (p < 0.01). Expression level of
      midkine gene in progressing B-ALL group was higher than that in progressing T-ALL
      (p < 0.01). The rhodamine 123 efflux test revealed that MFI in the leukemia cells
      was obviously lower than that in normal cells (p < 0.01), furthermore, there was
      an evident negative correlation between the MFI and MK mRNA expression (r = 
      0.869, p < 0.001). It is concluded that there is powerful drug efflux ability in
      lymphoblastic leukemia cells with high midkine gene expression. The midkine may
      take part in multidrug resistance.

PMID- 20030936
TI  - [Relation of HLA-DRB1*15 with pathogenesis in 162 childhood cases of acute
      lymphoblastic leukemia].
AB  - To unravel the relation of HLA-DRB1*15 with childhood acute lymphoblastic
      leukemia (ALL), 162 childhood patients with ALL were selected for this
      investigation. 1 000 normal umbilical cord blood samples were used as control.HLA
      DRB1*15 and HLA-DRB5* were typed by polymerase chain reaction (PCR) analysis. The
      relation of HLA-DRB1*15 with childhood ALL was studied by calculating the chi
      square test and relative risk. The results showed that the antigen frequencies
      and allele frequencies of HLA-DRB1*15 in childhood patients with ALL were 40.12%
      and 22.62% respectively, while the antigen frequencies and allele frequencies of
      HLA-DRB1*15 in control were 30.80% and 16.81% respectively, there were
      significant difference between them (chi(2) = 5.560, p = 0.018, RR = 1.506). In
      conclusion, the antigen frequencies and allele frequencies of HLA-DRB1*15 in
      childhood patients with ALL were higher than those in control, so the HLA-DRB1*15
      gene is one of the genetic risk factors for childhood ALL. These preliminary data
      may be useful for further study on the pathogenesis of childhood ALL.

PMID- 20030937
TI  - [Effect of 1,4-benzoquinone on growth of hematopoietic myeloid progenitor cells
      with IFN-gamma different genotypes].
AB  - This study was aimed to investigate the effect of 1,4-benzoquinone (1,4-BQ) on
      growth of myeloid progenitor cells with IFN-gamma different genotypes and to
      compare its differences. Polymerase chain reaction (PCR) was used to amplify the
      polymorphism gene segment of IFN-gamma +874 A/T in 36 cord blood (CB) specimens.
      The specimens were divided into three groups (AA, AT and TT group). MNCs were
      planted on complete methylcellulose medium containing different concentrations of
      1,4-BQ. The colony-forming units (CFU) were assayed, the differences of colony
      growth in specimens with different genotypes (AA, AT and TT) under 1,4-BQ
      exposure were analyzed. The results showed that frequencies of AA, AT and TT
      genotypes were 5.56%, 88.89% and 5.56% in the 36 CB samples respectively.
      Comparing colony numbers of IFN-gamma +874 AA, AT and TT genotype indicated that
      there was significant difference (p(AA) = 0.033, p(AT) = 0.009, p(TT) = 0.001, <
      0.05). Significant cytotoxicity was observed after exposure to concentrations of
      1,4-BQ > or = 5 micromol/L. Cytotoxic response of 1,4-BQ was dose-dependent.
      Under the same concentration of 1,4-BQ, there were no significant differences in
      capacity of cell colony growth between 3 groups (AA, AT and TT). Colony numbers
      of specimen No 3 in AT group and specimen No 2 in TT group were less than those
      of other specimens significantly. It is concluded that the hematopoietic myeloid
      progenitor cells cultured in the presence of 1,4-BQ show a dose-dependent
      cytotoxic response, but there are no significant differences in colony growth of
      IFN-gamma different genotypes (AA, AT and TT) under the same concentration of 1,4
      BQ.

PMID- 20030938
TI  - [Effect of ATRA on the expression of genes Hoxb2 and Hoxb4 in cord blood
      erythroid progenitors].
AB  - This study was aimed to investigate the expressions of genes hoxb2 and hoxb4
      after interference of the proliferation and differentiation of hematopoietic stem
      cells (HSC) to the erythroid progenitors (CFU-E) in vitro by using all-trans
      retinoic acid (ATRA). The cord blood was collected from 12 cases of fetal
      placenta umbilical vein and cultured by using culture technique of HSC in vitro.
      The proliferation and differentiation of HSC to CFU-E were interfered with 6 x
      10(-8) mol/L of ATRA. The expression levels of genes hoxb2 and hoxb4 in blank
      control and ATRA groups were detected by FQ-RT-PCR on day 3, 7 and 10 of culture.
      The results showed that the expressions of genes Hoxb2 and hoxb4 were a little on
      day 3, obviously increased on day 7 and reached highest level on day 10 in 2
      groups. The expression level of hoxb4 on day 3, 7 and 10 in blank control group
      was obviously higher than expression level of hoxb2. As compared with blank
      control group, the expressions of genes hoxb2 and hoxb4 in the ATRA group were
      significantly up-regulated. It is concluded that the genes hoxb2 and hoxb4 all
      expressed in process of proliferation and differentiation to erythroid
      progenitors, which suggests that hoxb2 and hoxb4 relate to erythroid
      hematopoiesis, and the hoxb4 has more great relevance to erythroid hematopoiesis
      as compared with hoxb2. The ATRA (6 x 10(-8) mol/L) can up-regulate the
      expression of hoxb2 and hoxb4 significantly.

PMID- 20030939
TI  - [Comparison between CMV quantitative PCR and CMV-pp65 antigen test for detection
      of CMV infection in allogeneic hematopoietic stem cell transplantation].
AB  - The study was aimed to compare the efficiency of cytomegalovirus (CMV)
      quantitative PCR and CMV-pp65 antigen test for detection of CMV infection and
      their clinical significance in patients received allogeneic hematopoietic stem
      cell transplantation (HSCT). 84 patients received allogeneic HSCT were enrolled
      in study. Anticoagulant blood samples were obtained from the recipients before
      and after transplantation and in the convalescence. CMV quantitative PCR and CMV
      pp65 antigen test were performed weekly. The results showed that out of 84
      patients, 26 cases were positive (30.95%) by CMV quantitative PCR method. Of the
      26 cases, 9 cases were CMV antigenemia and 13 cases were CMV disease, the median
      positive time was 37.1 (7 - 105) days after HSCT. 22 cases were positive (26.19%)
      by CMV-pp65 antigen test method, the median positive time was 46.6 (10 - 128)
      days after HSCT. All the 22 positive cases detected by CMV-pp65 antigen test were
      also positive by CMV quantitative PCR method. Nevertheless, 4 positive cases
      detected by CMV quantitative PCR but negative detected by CMV-pp65 antigen test
      method did not develop CMV disease. The CMV disease was found in the cases either
      with moderate to high copies of CMV quantitative PCR or moderate to high level
      CMV antigenemia by CMV-pp65 antigen test method. The clearance median time was
      17.5 (11 - 28) days by CMV quantitative PCR method after receiving antiviral
      therapy and was 10.0 (7 - 21) days by CMV-pp65 antigen detection method. It is
      concluded that both CMV quantitative PCR and CMV-pp65 antigen test can detect the
      infection of CMV early and effectively in patients received HSCT. CMV
      quantitative PCR is more sensitive, and CMV-pp65 is more specific. It can be more
      effective to guide the antiviral treatment and evaluate its efficacy when
      combining the two methods.

PMID- 20030940
TI  - [Changes of lymphocyte subsets in acute leukemia patients after HLA-mismatched
      nonmyeloablative hematopoietic stem cell transplantation].
AB  - This study was purposed to investigate the reconstitution of immune system in
      patients with acute lymphocyte leukemia (ALL) or acute myeloid leukemia (AML)
      after HLA-mismatched nonmyeloablative hematopoietic stem cell transplantation
      (NHSCT) and its relation with infection and GVHD. 6 ALL and 4 AML patients having
      HLA-mismatched related donors received the nonmyeloablative precondition regimen
      composed of fludarabine (Fln), ATG, Ara-C, CTX and total body irradiation (TBI)
      in dose 2 Gy. The GVHD was prevented and treated by CsA, anti-CD25 antibody and
      mycophenolic mofetil (MMF) before and after transplantation. The flow cytometry
      was used to detect the changes of total T cells, help/inducer T cells,
      suppressor/killer T cells, gamma/delta T cells, B cells, NK cells, NKT cells,
      regulatory T cells, activated T cells, naive T cells, memory T cells and ratio of
      CD4/CD8 in patients with remission resulting from chemotherapy before
      transplantation, and analyse the relation of immunofunctional cells to infection
      and GVHD after transplantation, compare the difference in recovery of immune
      system of ALL and AML patients. The results showed that the recovery of total
      lymphocytes and lymphocyte subsets displayed one's own regular pattern. As
      compared with patients without GVHD, the counts of lymphocyte subsets in patients
      with GVHD was higher, while the counts of gamma/delta T cells, regulatory T
      cells, NK cells, the counts of B cells, NK cells, naive cells and CD4/CD8 ratio
      as well as the counts of B cells, naive T cells and NK cells were lower at 1
      month, 2 - 3 months and 6 - 8 months after transplantation respectively. The
      total T cells and subsets recovered slowly, but NK cells and NKT cells recovered
      rapidly in patients with infection at early period after transplantation, the B
      cells and naive B cells recovered rapidly at 3 months after transplantation.
      There was no difference in lymphocyte recovery between ALL and AML patients. It
      is concluded that the analysis of each lymphocyte subsets may indirectly show the
      recovery of thymus function in patients, the changes of NK cells, B cells and
      naive T cells have an important significance for identifying and forecasting the
      GVHD and infection.

PMID- 20030941
TI  - [Effect of recombinant human tumor necrosis factor alpha on activity of
      gelatinase B and migration of human umbilical cord blood mononuclear cells in
      vitro].
AB  - This study was aimed to investigate the activity of matrix metalloproteinase-9
      (MMP-9) in umbilical cord blood mononuclear cells, the effect of recombinant
      human tumor necrosis factor alpha (rhTNF-alpha) on the activity of MMP-9 and cell
      migration capability of umbilical cord blood mononuclear cells, as well as the
      relationship between them. The different concentrations of TNF-alpha was added
      into the mononuclear cells. The activity of MMP-9 in umbilical cord blood
      mononuclear cells were analyzed by gelatinase spectrum. The cell migration
      capability was observed through the millicell carbine. The results showed that
      after umbilical cord blood mononuclear cells were cultured in serum-free RPMI
      1640 medium for 24 and 48 hours, the activity of MMP-9 could be detected, the
      cell migration capability at 24 and 48 hours were (1.371 +/- 0.011)% and (1.384
      +/- 0.014)% respectively, there was no statistical difference between them. Large
      dose of TNF-alpha (500 U/ml) led to the death of the cells; small doses of TNF
      alpha (< 200 U/ml) up-regulated the activity of MMP-9, and as the concentration
      of TNF-alpha increased, the activity of MMP-9 was enhanced. Small doses of TNF
      alpha (< 200 U/ml) improved the migration capability of umbilical cord blood
      mononuclear cells in a dose-dependent manner. It is concluded that small doses of
      TNF-alpha can upregulate the activity, enhance the migration capability of
      umbilical cord blood mononuclear cells, which probably accelerates cell homing
      after umbilical cord blood stem cell transplant and improves the hematopoietic
      reconstruction after transplantation.

PMID- 20030942
TI  - [Influence of intra-bone marrow infusion of donor lymphocytes on development of
      graft-versus-host disease and level of IL-4 and IFN-gamma in peripheral blood].
AB  - To investigate the effect of donor lymphocyte infusion (DLI) by intra-bone marrow
      (IBM) routes on the incidence of graft-versus-host disease(GVHD), level of IL-4
      and IFN-gamma after allogeneic peripheral hematopoietic stem cell transplantation
      (allo-PBSCT). Female C57BL/6 mice as recipients received total body irradiation
      (TBI) on day 0, followed by injection of peripheral hematopoietic stem cells from
      mobilized donor of male BALB/c with the granulocyte-colony stimulating factor
      (rhG-CSF), and DLI was performed via ether IV or IBM routes. The severity of GVHD
      was compared in recipients received allogeneic IBM-DLI with those mice received
      IV-DLI; at 14 days after DLI, the levels of IL-4 and interferon (IFN)-gamma were
      tested by ELISA. The results showed that as compared with IV-DLI group the
      frequency and severity of GVHD were reduced in IBM-DLI (p < 0.01); the level of
      IL-4 significantly increased, while the level of IFN-gamma decreased in group IV
      DLI (p < 0.01). It is concluded that IBM-DLI declines the incidence and severity
      of GVHD after allo-PBSCT.

PMID- 20030943
TI  - [Factors impacting yield of CD34(+) cells from healthy donors mobilized with rhG
      CSF].
AB  - This study was aimed to explore the effect of donor characteristics (age, sex and
      so on.) on CD34(+) cell yields in apheresis from healthy donors mobilized by
      recombinant granulocyte colony-stimulating factor(rhG-CSF). In 61 healthy donors,
      the characteristics associated with CD34(+) cell yield were analysed. The
      relationship between the CD34(+) cell yields and donor characteristics was
      statistically assessed with multivariate forward, backward and stepwise
      regression methods. A variety of parameters were analyzed which included donor
      age, sex, weight, height, body mass index (BMI) and time for collection of
      peripheral blood apheresis, while the mean number of peripheral blood mononuclear
      cells (MNCs), CD34(+) cell count, CD34(+) cell proportion based on MNC and
      CD34(+) cell count per kg of donor weight were used as the variables. The results
      showed that age of donors was the main factor impacting CD34(+) cell yields (
      0.60 < r < -0.45, p < 0.005). In a partial correlation analysis the body weight,
      height and BMI were served as control factors, the negative correlation of age
      with CD34(+) cell yields was still found (-0.50 < r < -0.35, p < 0.02). BMI was
      only weakly correlated with the yields of CD34(+) cells per kg(r = -0.297, p <
      0.05). As a whole, sex showed no relation with the CD34(+) cell yields. Compared
      with the female group less than 35 years old, height, weight and BMI in male
      group of low age exerted a positive impact on CD34(+) cell yield. The optimal
      time for collection of PB was day 4 after treatment with rhG-CSF, when 70% of the
      donors could reach the peak CD34(+) cell yields. It is concluded that the age of
      the donors is the first factor determining the choice of donors for allogeneic
      hematopoietic stem cell transplantation, the sex, height, weight and BMI are
      secondary factors impacting yield of CD34(+) cells from donors mobilized with rhG
      CSF.

PMID- 20030944
TI  - [Effects of anti-TGF-beta1 monoclonal antibody on in vitro expansion of cord
      blood CD34(+) cells].
AB  - In order to investigate the effect of anti-TGF-beta1 monoclonal antibody on the
      expansion of cord blood CD34(+) cells, the purified cord blood CD34(+) cells were
      divided into three groups: blank control group: purified cord blood CD34(+) cells
      cultured on day 0; control group: cells cultured for 3 days in the culture
      system, containing SCF, IL-3, IL-6 and FLT3-L; test group: cells cultured for 3
      days in the same culture system as control group, but with anti-TGF-beta1
      monoclonal antibody. The mononuclear cell counting (MNC), the expression of CD34
      and c-kit, and CFU-GEMM, BFU-E and CFU-GM counting were detected in all three
      groups. The result showed that the expansion of MNCs, CD34(+) cells and CD34(+)c
      kit(+) cells in test group [(2.35 +/- 0.25) x 10(5), (1.16 +/- 0.29) x 10(5),
      (1.09 +/- 0.26) x 10(5)] was significantly higher than that in control group
      [(1.25 +/- 0.13) x 10(5), (0.55 +/- 0.19) x 10(5), (0.51 +/- 0.2) x 10(5)](p <
      0.01). The expansion of more primitive CD34(+)c-kit(-) subpopulation in test
      group [(12.95 +/- 3.17) x 10(3)] was even significantly higher than in control
      group (1.71 +/- 0.83) x 10(3) (p < 0.01). Colony forming assay showed that the
      number of earlier progenitor colony CFU-GEMM, BFU-E in test group [(16.3 +/-
      4.72) x 10(3), (60.5 +/- 20.96) x 10(3)] was higher than that in control group
      [(5.0 +/- 2.58) x 10(3), (16.25 +/- 7.93) x 10(3)] (p < 0.01). The number of
      relatively mature CFU-GM between test group and control group was not statistical
      significance [(6.33 +/- 2.85) x 10(3) vs (4.0 +/- 2.28) x 10(3)](p > 0.05), but
      both were higher than that in blank group (0.75 +/- 0.29) x 10(3). These results
      demonstrated that anti-TGF-beta1 monoclonal antibody promoted the expansion of
      MNC and CD34(+) cells, and even more marked expansion of the more primitive
      progenitor cells-CD34(+)c-kit(-) cells. Meanwhile, it enhanced the output of more
      immature colony CFU-GEMM and BFU-E, but had no evident influence on the mature
      myeloid colony CFU-GM. It is concluded that the anti-TGF-beta1 monoclonal
      antibody can synergize other cytokines to enhance the proliferation of cord blood
      CD34(+) progenitor cells effectively, and it is more important that can reserve
      more primitive progenitor cells.

PMID- 20030945
TI  - [Effect of inflammatory cytokines on the expression of Krupple-like factor 4 in
      endothelium].
AB  - The aim of this study was to investigate the expression of Krupple-like factor 4
      (KLF-4) in human umbilical vein endothelial cells (HUVEC) under stimulating of
      cytokines IL-1beta and TNF-alpha. The HUVEC were isolated, cultured and exposed
      to IL-1beta, TNF-alpha for 2 and 4 hours, the expression level of KLF-4 mRNA was
      detected by real-time PCR, the expression level of KLF-4 protein was measured by
      Western blot, the location of KLF-4 in HUVEC was determined by confocal laser
      microscopy. The results showed that the KLF-4 mRNA lowly expressed in normal
      HUVEC, but highly expressed in HUVEC after stimulation with IL-1beta and TNF
      alpha; furthermore the expressions of KLF-4 mRNA and protein were enhanced along
      with prolonging of time. Confocal laser microscopy showed that the expression of
      KLF-4 was enhanced in nucleus and plasma of HUVEC after stimulating with IL
      1beta. It is concluded that the expression of KLF-4 increases under IL-1beta and
      TNF-alpha stimulation which may participate in regulation of endothelial
      activity.

PMID- 20030946
TI  - [PI3-kinase mediates activity of RhoA and interaction of RhoA with mDia1 in
      thrombin-induced platelet aggregation].
AB  - The aim of this study was to investigate the role of RhoA/mDia1 pathway in the
      process of thrombin-induced platelet aggregation and regulatory effect of PI3K
      inhibitor on this process. The human platelets were isolated from peripheral
      blood, the activation of RhoA, Rac1 and Cdc42 in the platelet aggregation was
      detected by GST pull-down assay and immune co-precipitation, the interaction of
      RhoA, Rac1 and Cdc42 with mDia1 and the formation of complex in the process of
      platelet aggregation were determined by immune coprecipitation, and the effect of
      PI3K inhibitor (wortmannin) on above-mentioned process was assayed. The results
      showed that thrombin elevated the activity of RhoA and the binding capability of
      RhoA with mDia1 during thrombin-induced platelet aggregation and spreading on Fg
      coated coverslips. Wortmannin inhibited the rising of RhoA activity and the
      binding level of RhoA with mDia1 induced by thrombin. Thrombin elevated the
      activity of Rac1 and Cdc42 during thrombin-induced platelet aggregation, but
      could not induce binding of Rac1 or Cdc42 with mDia1. Wortmannin could not
      inhibit the rising of Rac1 and Cdc42 activity induced by thrombin. It is
      concluded that the PI3-kinase regulates the thrombin-induced actin cytoskeleton
      reconstitution in platelets by RhoA-mDia1 pathway.

PMID- 20030947
TI  - [Establishment of Chinese hamster ovary cell line expressing recombinant GPIb-IX
      complex].
AB  - The aim of this study was to construct Chinese Hamster Ovary (CHO) cell models
      expressing recombinant wild-type GPIb-IX and mutant GPIb-IX complex, so as to
      provide the platform to study the related physiologic functions of GPIb-IX. The
      plasmids were extracted from E.coli expressing wild-type or deletion mutant
      GPIbalpha and were identified by digestion with EcoR I. Three plasmids containing
      GPIbalpha, GPIbbeta, and GPIX genes were co-transfected into CHO cells, and then
      the expression of GPIb-IX complex was detected by immune coprecipitation, Western
      blot and flow cytometry. The results showed that the expression of GPIb-IX
      complex could be detected in the lysate and on the surface of CHO cells at 48
      hours after transfection. In conclusion, CHO cell models expressing recombinant
      wild-type or mutation GPIb-IX complex has been successfully constructed.

PMID- 20030948
TI  - [Toll-like receptor 4 expression mediates the activation of platelets induced by
      LPS].
AB  - The study was aimed to investigate the expression of Toll-like receptor 4 (TLR4)
      on platelets and to determine whether platelet TLR4 involves in its activation
      induced by lipopolysaccharide (LPS). Human platelet-rich plasma (PRP) and
      platelet suspension obtained from 15 healthy individuals pretreated with a
      concentration of 0.2 microg/ml of LPS in the presence or absence of thrombin (1
      U/ml) for 1 hour. The expressions of TLR4, CD62P (P-select) and CD40L on
      platelets were detected by flow cytometry, and platelet TLR4 expression was
      further determined by Western blot analysis. The results indicated that the
      percentage of TLR4-positive platelets induced by thrombin was increased by 32.34%
      compared with the resting platelets (25.44%, p < 0.05). TLR4 expression on
      platelets treated with LPS was remarkably elevated in the presence or absence of
      thrombin. However, the expression level of the former was much higher than that
      of the latter and thrombin stimulation alone (p < 0.05). Moreover, the similar
      results were found in Western blot analysis. Synchronously, expressions of CD62P
      and CD40L on resting platelets were 6.39% and 2.45%, they were also markedly
      increased when treated with thrombin (42.68% and 14.8%) and LPS respectively, and
      the increases of expression of CD62P and CD40L were more significant when
      stimulated with both LPS and thrombin (63.03% and 13.94%). Although anti-TLR4
      antibody inhibited significantly the increase of TLR4, CD62P and CD40L on
      platelets induced by LPS, which did not affect their increase induced by
      thrombin. In conclusion, the evidence has been shown that functional TLR4 can be
      expressed on human platelets. It may involve in platelet activation as an
      important mediator of LPS-induced CD62P and CD40L expressions on platelets.

PMID- 20030949
TI  - [Polymorphism of DXS15, CA13, CA22 loci in Guangdong normal population].
AB  - The aim of this study was to investigate the polymorphism of microsatellite
      repeats DXS15, CA13, CA22 tightly linked to FVIII gene in Guangdong population
      and its practical value in genetic diagnosis for hemophilia A. The polymerase
      chain reaction (PCR) and capillary electrophoresis (CE) methods were adopted to
      test the variability of the 3 microsatellite repeat in Guangdong females,
      including 111 females, 222 X chromosomes for detecting DXS15 polymorphism; 87
      females, 174X chromosomes for detecting CA13 polymorphism; 94 females, 188 X
      chromosomes for detecting CA22 polymorphism. The results indicated that 11
      alleles corresponding to DXS15 were found at this locus with size ranging from
      140 to 160 bp. The polymorphism information content (PIC) of this microsatellite
      repeat was 0.82, heterozygosity was 82%. Six alleles corresponding to CA13 were
      found, with a size from 145 to 155 bp, and PIC was 0.56, heterozygosity was
      56.2%. Four alleles corresponding to CA22 were found with size ranging from 79 to
      85 bp, and PIC was 0.41, heterozygosity was 50%. It is concluded that in contrast
      to the information about Caucasian, the polymorphism of these 3 microsatellites
      differs from race to race, and region to region. DXS15, CA13 and CA22 are highly
      polymorphic genetic markers useful for linkage analysis of haemophilia A, which
      may play a vital role in detection and prenatal diagnosis for hemophilia A.

PMID- 20030950
TI  - [Retrospective analysis of 71 cases of multiple myeloma].
AB  - The aim of this study was to investigate the efficacy of different chemotherapy
      regimens in patients with multiple myeloma (MM). The therapeutic effects of 71 MM
      patients receiving standard chemotherapy regimens were retrospectively analyzed
      and evaluated. The results showed that 44 out of 71 new-diagnosed MM patients
      gained remission in varying degree, total effective rate was 61.9%, in which the
      rate of complete remission (CR) plus nearly complete remission (nCR) was 21.1%.
      21 MM patients received M2 regimen gained total effective rate of 57.1%, in which
      the CR plus nCR were found in 5 MM patients, and partial remission (PR) was
      observed in 7 MM patients. 8 MM patients received MP chemotherapy regimen gained
      total effective rate of 37.5%, in which the CR + nCR was not found, but the PR
      was observed in 3 MM patients. 30 MM patients received VAD regimen gained total
      effective rate of 63.3%, in which CR + nCR and PR were found in 6 and 13 MM
      patients respectively, 12 MM patients received combined bortezomib regimen gained
      total effective rate of 83.3%, in which CR + nCR and PR were found in 4 and 6 MM
      patients respectively. The median time of progression and the median time of
      survival in 72 MM patients were 22.1 and 29.5 months respectively. The 3 and 5
      year survival rates in 72 MM patients were 41.2% and 20.6% respectively. In
      conclusion, the chemotherapy regimen for new-diagnosed MM patients should be
      selected according to their clinical features and subtypes, the bortezomib
      combined regimen may be considered as a new and effective regimen for MM
      patients.

PMID- 20030951
TI  - [FLAG regimen as consolidation therapy for patients with acute myeloid leukemia].
AB  - The objective of study was to primarily explore the efficacy of combination of
      high doses cytarabine, fludarabine and G-CSF (FLAG) as the consolidation therapy
      for patients with acute myeloid leukemia (AML), and to analyze the influence of
      FLAG on peripheral stem cell mobilization. 31 patients with AML in complete
      remission were divided into two groups based on induction regimens, e.g. IA group
      (idarubicin and cytarabine) and non-IA group. All patients were consolidated with
      FLAG regimen which including fludarabine 50 mg/d, days 1-5; Ara-C 2 g/(m(2).d),
      days 1-5; G-CSF 300 microg/d. Time of its use sustained from day 0 until absolute
      neutrophil count > 1.0 x 10(9)/L. 17 patients received 2 or 3 courses of FLAG
      regimen, and 14 patients took 1 course. 9 patients received 2 courses of FLAG
      regimen as consolidation therapy, and then peripheral stem cells were collected
      from them. The results showed that sufficient peripheral stem cells were obtained
      in 7 out of 9 patients (77.8%) after 2 courses of FLAG regimen, however one
      patient failed to obtain sufficient CD34(+) cells after 3 courses. 6 patients
      received autologous stem cell transplantation, 3 patients received allogeneic
      stem cell transplantation, and 7 cases received 2 courses of Ara-c after treating
      with mitoxantrone or daunorubicin. One patient died within 4 weeks. 9 patients
      relapsed. The median survival duration was 14 (1 - 46) months and median disease
      free survival time was 12 (2 - 45) months. There was no significant difference
      for OS and DFS between IA and non-IA groups. Myelosuppression and infections due
      to neutropenia were the most frequent adverse effects, severe nonhematologic
      toxicities were not observed in all patients. It is concluded that as
      consolidation regimen, the FLAG is an effective and well-tolerated treatment in
      AML with acceptable toxicity, and may not influence the peripheral stem cell
      mobilization for autologous stem cell transplantation after 2 courses of FLAG.

PMID- 20030952
TI  - [Preliminary study on rehydrated conditions for lyophilized human red blood
      cells].
AB  - The objective of this study was to investigate the effect of different
      rehydration conditions on recovery of the lyophilized red blood cells (RBC) so as
      to optimize the RBC rehydration. The different conditions, including different
      rehydration solution, the rehydration temperature, volume change rate of the
      lyophilized RBC rehydrated by the vapor firstly, were studied, the recovery rate
      and change of physiological and biochemical properties of the rehydrated RBC were
      detected. The results indicated that the solution of 10% (w/v) PVP40 in PBS
      showed the best effect, and the RBC recovery rate increased with increasing of
      rehydration temperature, and the optimal temperature of rehydration was at 37
      degrees C. Pre-rehydration in condition of vapor could raise the RBC recovery
      rate, and promote the MCV and RDW to close to index of the fresh RBC, the
      deformability of the rehydrated RBC was no serious as compared with RBC preserved
      in conventional condition, but the activity level of ATP, G-6-PD, SOD, 2, 3-DPG
      of the rehydrated RBC less decreased. It is concluded that the optimal
      rehydration conditions for lyophilized RBC are pre-rehydration in the 37 degrees
      C with vapor firstly, PBS + 10% (w/v) PVP40 rehydration solution and rehydration
      temperature at 37 degrees C, but the protection of RBC membrane needs to be
      furtherly studied.

PMID- 20030953
TI  - [Impact of immunoglobulin gene somatic high mutation on prognosis of the chronic
      lymphocytic leukemia].
AB  - There are great differences in the clinical process and prognosis of the chronic
      lymphocytic leukemia(CLL), the precise diagnosis is of importance to judge
      prognosis, guide therapy and research pathogenesis mechanism. The variable region
      mutation of immunoglobulin heavy chain is the most stable molecular index of
      disease prediction. The patients with sequence of IgHV somatic high mutation
      usually have a better prognosis and a more longer survival time than those
      without the mutation. The recent study has found that specific IgHV gene
      expression also can predict the disease outcome in some cases regardless of
      mutation. The clinical prognosis of CLL patients can be further stratified by
      specific IgHV gene expression. In this review, the progress in the research of
      the clinical significance of specific IgHV gene expression in the chronic
      lymphocytic leukemia is summarized.

PMID- 20030954
TI  - [Advances of study on PPARgamma/PPARgamma ligand in hematologic malignancies].
AB  - Recently, along with the thorough investigation on the gene and molecular biology
      of peroxisome proliferators activated receptorgamma (PPARgamma), the therapeutic
      effects of PPARgamma ligand and its potential mechanism were gradually
      recognized. PPARgamma will probably become a new target of oncotherapy and is now
      extensively followed by researchers. This review focuses the advances of study on
      PPARgamma distribution in tissue, its function, its ligand in relationship with
      hematologic malignancies including acute myeloid leukemia, acute lymphocytic
      leukemia, chronic myeloid leukemia, lymphoma, multiple myeloma and so on.

PMID- 20030955
TI  - [Mechanism and problem of amifostine in treating myelodysplastic syndromes].
AB  - Myelodysplastic syndrome (MDS) is one of the most prevalent haematological
      malignancies originating from haemopoietic stem/progenitor cells. MDS
      characterized by morbid haematopoiesis of bone marrow and peripheral blood cell
      reduction and mainly occurs in the elders. The dangerous factors of MDS include
      chemotherapy, radiotherapy, benzene, other organic solvent, immune depressants
      and so on. Following the recent progress of medical sciences, a large number of
      new regimens of chemotherapy, radiotherapy and immune therapy against carcinomas
      generate and lead the development of therapeutics for malignancies. It is worried
      that the incidence of MDS still increases year by year and the patient age
      becomes younger. Although many agents are used to MDS, curative effect is not as
      good as expect. Amifostine, a kind of pancytoprotector also used in treatment of
      MDS. This review summarizes the mechanism of amifostine in MDS therapy which
      possesses a challenge binding with the current related investigations.

PMID- 20030956
TI  - [Progress of study on the detection technique of microRNA].
AB  - MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate
      gene expression via degradation or translational repression of their targeted
      mRNAs. MiRNAs are involved in critical biologic processes, including development,
      cell differentiation, proliferation and the pathogenesis of disease. This review
      focuses on recent researches on the detection techniques of miRNA including
      micorarray technique, Northern blot, real-time quantitative PCR, detection
      technique of miRNA function and so on.

PMID- 20030957
TI  - [Immunoregulatory function of mesenchymal stem cells and application of
      mesenchymal stem cells in therapy of autoimmune disease].
AB  - Mesenchymal stem cells (MSCs) are multipotent cells derived from many adult
      tissues, which can differentiate into cells of the mesodermal lineage, such as
      adipocyte, osteocyte and chondrocyte, as well as cells of other embryonic
      lineages. They are a promising tool for tissue engineering. In addition, MSC
      interacts with immune system, suppressing T cell, B cell and NK cell function and
      dendritic cell activities. MSC migrates to injured tissue to promote the survival
      of damaged cells and induces peripheral immune tolerance. The role of MSC in
      reducing the incidence and severity of graft versus host disease (GVHD)
      clinically has recently been reported. The immunoregulatory function of MSCs also
      shows a growing promise in the therapeutic application in autoimmune diseases.
      This review discusses the mechanism of MSC immunomodulatory ability and its
      therapeutic potential in autoimmune diseases.

PMID- 20030958
TI  - [Individualizing treatment of refractory and relapsed ITP in adults and its
      development of study].
AB  - Idiopathic thrombocytopenic purpura (ITP) is a common hematological disease. It
      bleeds with peripheral blood platelet reduction as the main clinical
      manifestation, and manifests a chronic history in adult people. 11% - 35% ITP
      patients develop into a refractory course, which may be related with gene
      polymorphisms. There is currently no consensus on how best to manage
      refractory/relapsed ITP. In part, this reflects the need for individualized
      treatment due to the patients' requirements and their responsiveness to
      therapies. The objective of this review is to provide a clinically useful guide
      to current management strategies. This article summarizes all the treatment for
      refractory ITP, and highlights new therapies, including the anti-CD20 antibody,
      thrombopoietic agents, TPO receptor agonist and HSCT. The pancytoprotector shows
      good effect in the treatment of refractory and relapsed ITP in China. In a word,
      to give different treatments individually is most important.

PMID- 20030959
TI  - [New insights on hepcidin in anemia of chronic disease].
AB  - Anemia of chronic disease is normocytic and normochromic. One of the mechanisms
      is misbalance of iron metabolism. Hepcidin, a kind of protein secreted by liver
      is considered to be the hormone regulating iron metabolism. It binds to
      ferroportin and induces the latter one's internalization. Thus, iron
      transportation from iron storage cells to serum is reduced. Cytokines are
      elevated in chronic disease. They stimulate hepcidin expression in liver through
      JAK2/STAT3 pathway. As a result, iron absorption and reabsorption is blocked,
      which leads to the misbalance of iron metabolism in anemia of chronic disease. In
      this article, the hepcidin and its relation to iron metabolism and anemia in
      chronic disease are reviewed.

PMID- 20030960
TI  - [Current approaches to diagnosis and treatment of invasive fungal infection in
      HSCT recipients].
AB  - Invasive fungal infections (IFI) are a kind of the most severe complications
      after hematopoietic stem cell transplantation (HSCT), Candida and Aspergillus are
      common causes. Because of immunosuppressive therapy, ablative conditioning
      regimen, acute or chronic graft-versus-host disease, long-term treatment of broad
      spectrum antibiotics and cytomegalovirus infection, IFI has increased in the past
      few years. Invasive mould infection is a major cause of morbidity and mortality
      in HSCT recipients. Methods for early diagnosis of IFI include clinical and
      laboratory examinations, as well as characteristic radiography. Voriconazole is
      the first-line antifungal agent for prevention of IFI. Combination therapy of two
      antifungal compounds such as azoles or amphotericin B with echinocandins have
      shown a good effectiveness and may be a promising future strategy for antifungal
      treatment. In this review, the early diagnosis and treatment of IFI in HSCT
      recipients are summarized. As for early diagnosis of IFI, the laboratory
      diagnosis techniques such as GM test, G test and PCR techniques are discussed. As
      for prophylaxis and treatment of IFI, the prophylaxis treatment, empirical
      treatment, preemptive treatment, targeted treatment, combined treatment and
      immunologic treatment are discussed.

PMID- 20030961
TI  - [Recent advances on extranodal NK/T-cell lymphoma of nasal type].
AB  - Extranodal NK/T-cell lymphoma, nasal type (ENKT), is a distinct clinicopathologic
      disease, common among East Asia and Latin America population. Clinically, it
      frequently occurs in middle-aged men. It predominantly occurs in the nasal or
      paranasal areas and less frequently in the skin. The main clinical features are
      nasal congestion, sore throat, dysphagia and epistaxis, due to a destructive mass
      involving the midline facial tissues. The pathogenesis of ENKT remains uncertain.
      It is thought that Epstein-Barr virus (EBV) may play a role in the development of
      this entity. Pathologically, lymphoma cells exhibit angioinvasion,
      angiodestruction and coagulative necrosis. It has unique characteristics
      including the expression of cytoplasmic CD3, CD56 and cytotoxic molecules such as
      TIA-1, and is positive for EBV in situ hybridization. The overall prognosis of
      this disease is poor because of frequent relapse or resistance to treatment.
      Although several studies have explored the treatment of ENKL in recent years, the
      optimal therapy has still not been found. Due to the highly aggressive features
      of tumors, every endeavor has been made to investigate factors associated with
      poor outcome. In this review, the recent advances on cause and pathogenesis,
      clinical manifestations and staging, pathologic characteristics, diagnosis and
      differential diagnosis, therapy and prognosis of ENKL are summarized.

PMID- 20030962
TI  - [Research progress on gene mutation of jak2].
AB  - Chronic myeloproliferative disease (CMPD) is a group of malignant blood disorders
      including polycythemia vera, essential thrombocythemia, primary myelofibrosis,
      chronic myeloid leukemia, and so on. CMPD is characterized by proliferation of
      one or several lineages in hematopoietic system. The pathogenesis of CMPD is not
      clear except chronic myeloid leukemia associated with the bcr/abl fusion gene. In
      recent years, more studies demonstrated that CMPD have a higher mutation rate of
      gene jak2. In this review, the association of jak2 gene mutation with clinical
      diagnosis, clinical feature and molecular target therapy in CMPD and other
      hematological disease were summarized.

PMID- 20030963
TI  - Perceived vulnerability as a common basis of moral emotions.
AB  - It is theorized that many moral emotions are triggered when a mechanism for
      (parental) care is activated by perceived vulnerability, and changes in the care
      object's well-being are subsequently evaluated and causally attributed.
      Participants reported different moral emotions (tenderness, concern, sympathy,
      guilt, and moral anger) in relation to different photographs of males and females
      widely differing in age. Using variation between emotion objects, it was shown
      that emotional reactions were highly intercorrelated and strongly related to
      perceived vulnerability and aroused protective tendency; with children and
      elderly arousing the strongest, and adult males the weakest, emotions. Moreover,
      these intercorrelations largely disappeared when vulnerability and protective
      tendency were statistically controlled. Theoretical implications are discussed.

PMID- 20030964
TI  - A comparison of statistical selection strategies for univariate and bivariate log
      linear models.
AB  - In this study, eight statistical selection strategies were evaluated for
      selecting the parameterizations of log-linear models used to model the
      distributions of psychometric tests. The selection strategies included
      significance tests based on four chi-squared statistics (likelihood ratio,
      Pearson, Freeman-Tukey, and Cressie-Read) and four additional strategies (Akaike
      information criterion (AIC), Bayesian information criterion (BIC), consistent
      Akaike information criterion (CAIC), and a measure attributed to Goodman). The
      strategies were evaluated in simulations for different log-linear models of
      univariate and bivariate test-score distributions and two sample sizes. Results
      showed that all eight selection strategies were most accurate for the largest
      sample size considered. For univariate distributions, the AIC selection strategy
      was especially accurate for selecting the correct parameterization of a complex
      log-linear model and the likelihood ratio chi-squared selection strategy was the
      most accurate strategy for selecting the correct parameterization of a relatively
      simple log-linear model. For bivariate distributions, the likelihood ratio chi
      squared, Freeman-Tukey chi-squared, BIC, and CAIC selection strategies had
      similarly high selection accuracies.

PMID- 20030965
TI  - Estimation of a four-parameter item response theory model.
AB  - We explore the justification and formulation of a four-parameter item response
      theory model (4PM) and employ a Bayesian approach to recover successfully
      parameter estimates for items and respondents. For data generated using a 4PM
      item response model, overall fit is improved when using the 4PM rather than the
      3PM or the 2PM. Furthermore, although estimated trait scores under the various
      models correlate almost perfectly, inferences at the high and low ends of the
      trait continuum are compromised, with poorer coverage of the confidence intervals
      when the wrong model is used. We also show in an empirical example that the 4PM
      can yield new insights into the properties of a widely used delinquency scale. We
      discuss the implications for building appropriate measurement models in education
      and psychology to model more accurately the underlying response process.

PMID- 20030966
TI  - Cocaine addiction and personality: a mathematical model.
AB  - The existence of a close relation between personality and drug consumption is
      recognized, but the corresponding causal connection is not well known. Neither is
      it well known whether personality exercises an influence predominantly at the
      beginning and development of addiction, nor whether drug consumption produces
      changes in personality. This paper presents a dynamic mathematical model of
      personality and addiction based on the unique personality trait theory (UPTT) and
      the general modelling methodology. This model attempts to integrate personality,
      the acute effect of drugs, and addiction. The UPTT states the existence of a
      unique trait of personality called extraversion, understood as a dimension that
      ranges from impulsive behaviour and sensation-seeking (extravert pole) to fearful
      and anxious behaviour (introvert pole). As a consequence of drug consumption, the
      model provides the main patterns of extraversion dynamics through a system of
      five coupled differential equations. It combines genetic extraversion, as a
      steady state, and dynamic extraversion in a unique variable measured on the
      hedonic scale. The dynamics of this variable describes the effects of stimulant
      drugs on a short-term time scale (typical of the acute effect); while its mean
      time value describes the effects of stimulant drugs on a long-term time scale
      (typical of the addiction effect). This understanding may help to develop
      programmes of prevention and intervention in drug misuse.

PMID- 20030967
TI  - Separating response-execution bias from decision bias: arguments for an
      additional parameter in Ratcliff's diffusion model.
AB  - Diffusion model data analysis permits the disentangling of different processes
      underlying the effects of experimental manipulations. Estimates can be provided
      for the speed of information accumulation, for the amount of information used to
      draw conclusions, and for a decision bias. One parameter describes the duration
      of non-decisional processes including the duration of motor-response execution.
      In the default diffusion model, it is implicitly assumed that both responses are
      executed with the same speed. In some applications of the diffusion model, this
      assumption will be violated. This will lead to biased parameter estimates.
      Consequently, we suggest accounting explicitly for differences in the speed of
      response execution for both responses. Results from a simulation study illustrate
      that parameter estimates from the default model are biased if the speed of
      response execution differs between responses. A second simulation study shows
      that large trial numbers (N>1,000) are needed to detect whether differences in
      response-execution times are based on different execution times.

PMID- 20030968
TI  - Detecting a lack of association: an equivalence testing approach.
AB  - Researchers often test for a lack of association between variables. A lack of
      association is usually established by demonstrating a non-significant
      relationship with a traditional test (e.g., Pearson's r). However, for logical as
      well as statistical reasons, such conclusions are problematic. In this paper, we
      discuss and compare the empirical Type I error and power rates of three lack of
      association tests. The results indicate that large, sometimes very large, sample
      sizes are required for the test statistics to be appropriate. What is especially
      problematic is that the required sample sizes may exceed what is practically
      feasible for the conditions that are expected to be common among researchers in
      psychology. This paper highlights the importance of using available lack of
      association tests, instead of traditional tests of association, for demonstrating
      the independence of variables, and qualifies the conditions under which these
      tests are appropriate.

PMID- 20030969
TI  - Bayesian analysis of mixtures in structural equation models with non-ignorable
      missing data.
AB  - Structural equation models (SEMs) have become widely used to determine the
      interrelationships between latent and observed variables in social,
      psychological, and behavioural sciences. As heterogeneous data are very common in
      practical research in these fields, the analysis of mixture models has received a
      lot of attention in the literature. An important issue in the analysis of mixture
      SEMs is the presence of missing data, in particular of data missing with a non
      ignorable mechanism. However, only a limited amount of work has been done in
      analysing mixture SEMs with non-ignorable missing data. The main objective of
      this paper is to develop a Bayesian approach for analysing mixture SEMs with an
      unknown number of components and non-ignorable missing data. A simulation study
      shows that Bayesian estimates obtained by the proposed Markov chain Monte Carlo
      methods are accurate and the Bayes factor computed via a path sampling procedure
      is useful for identifying the correct number of components, selecting an
      appropriate missingness mechanism, and investigating various effects of latent
      variables in the mixture SEMs. A real data set on a study of job satisfaction is
      used to demonstrate the methodology.

PMID- 20030972
TI  - Society for applied spectroscopy - presidential reflections.

PMID- 20030973
TI  - Mining the information content buried in infrared and near-infrared band shapes
      by temporal, spatial, and other perturbations.

PMID- 20030974
TI  - A chemometric analysis of ligand-induced changes in intrinsic fluorescence of
      folate binding protein indicates a link between altered conformational structure
      and physico-chemical characteristics.
AB  - Ligand binding alters the conformational structure and physico-chemical
      characteristics of bovine folate binding protein (FBP). For the purpose of
      achieving further information we analyzed ligand (folate and methotrexate)
      induced changes in the fluorescence landscape of FBP. Fluorescence excitation and
      emission two-dimensional (2D) spectra were recorded over a wide range of
      wavelengths on a Perkin-Elmer LS 55 spectrofluorometer at varying pH in different
      buffers, and the resulting three-dimensional data were subjected to a chemometric
      analysis, parallel factor analysis (PARAFAC). The most important finding was the
      occurrence of two maximum intensity emission wavelengths of tryptophan, 350 nm
      (component one) and 330 nm (component two). In contrast to the first component,
      the score of the short wavelength component increased with increasing ligation of
      FBP. Since the emission wavelengths of indole groups in tryptophan shorten with
      increasing distance from the solvent surface of proteins, an increasing number of
      the 11 tryptophan residues seem to reorientate from the solvent surface to the
      interior of FBP with increasing ligation. The sharp decrease in hydrophobicity at
      pI=7-8 following binding of folate accords fairly well with the disappearance of
      strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP.
      The PARAFAC has thus proven useful to establish a hitherto unexplained link
      between parallel changes in conformational structure and physico-chemical
      characteristics of FBP induced by folate binding. Parameters for ligand binding
      derived from PARAFAC analysis of the fluorescence data were qualitatively and
      quantitatively similar to those obtained from binding of radiofolate to FBP.
      Herein, methotrexate exhibited a higher affinity for FBP than in competition with
      radiofolate. This could suggest a rapid and firm complexation of folate to FBP,
      blocking access of competing ligands.

PMID- 20030975
TI  - Application of the Kubelka-Munk correction for self-absorption of fluorescence
      emission in carmine lake paint layers.
AB  - The variations of the fluorescence emission of carmine lake travelling through an
      absorbing and scattering medium, such as a paint layer, were investigated by
      ultraviolet (UV)-visible absorption, fluorescence spectroscopy, and imaging
      techniques. Samples of the lake were studied in dilute and saturated solutions,
      on a reference test panel and a real case study. Relevant spectral modifications
      have been observed as a function of the lake concentration mainly consisting of a
      fluorescence quenching, red shift of emission maxima, and deformation of emission
      band. The application of a correction factor based on the Kubelka-Munk model
      allowed fluorescence spectra obtained in solution and on painted samples of known
      composition to be compared and correlated, highlighting that the fluorescence of
      the lake within paint layers is affected by both self-absorption and aggregation
      phenomena. This approach has been successfully applied on a painting by G. Vasari
      for the noninvasive identification of carmine lake. The results reported here
      emphasize the necessity of taking physical phenomena into account in the
      interpretation of the fluorescence spectra for a proper and reliable
      characterization and identification of painting materials in works of art.

PMID- 20030976
TI  - Study on the genotoxic interaction of methyl violet with calf thymus DNA.
AB  - By utilizing ultraviolet (UV)-visible absorption spectroscopy, circular dichroism
      (CD), resonance light scattering (RLS), and transmission electron microscope
      (TEM) techniques, the toxic interaction of methyl violet (MV) with calf thymus
      DNA (ctDNA) was investigated at the molecular level. The UV-visible absorption
      spectra results showed that MV intercalated into ctDNA base pairs at low MV
      concentrations, while MV was attached to the negative charged phosphate groups at
      higher concentrations and the binding constant (K(theta)(25 degrees C)) was 1.80
      x 10(3) L mol(-1). The absorbency results showed that the genotoxic interaction
      of MV with ctDNA is under the electrostatic binding mode. MV had strong toxic
      interaction with ctDNA at 4.0 x 10(-5) mol L(-1) MV and pH 6.5. The toxic
      interaction of MV with ctDNA can result in the formation of massive aggregates
      and change of the ctDNA conformation, which showed a significant linear dose
      response relationship.

PMID- 20030977
TI  - Molecular spectral imaging system for quantitative immunohistochemical analysis
      of early diabetic retinopathy.
AB  - A molecular spectral imaging system has been developed based on microscopy and
      spectral imaging technology. The system is capable of acquiring molecular
      spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic
      principles, instrumental systems, and system calibration method as well as its
      applications for the calculation of the stain-uptake by tissues are introduced.
      As a case study, the system is used for determining the pathogenesis of diabetic
      retinopathy and evaluating the therapeutic effects of erythropoietin. Some
      molecular spectral images of retinal sections of normal, diabetic, and treated
      rats were collected and analyzed. The typical transmittance curves of positive
      spots stained for albumin and advanced glycation end products are retrieved from
      molecular spectral data with the spectral response calibration algorithm. To
      explore and evaluate the protective effect of erythropoietin (EPO) on retinal
      albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on
      Beer-Lambert's law is presented. The algorithm can assess the uptake by
      histologic retinal sections of stains used in quantitative pathology to label
      albumin leakage and advanced glycation end products formation. Experimental
      results show that the system is helpful for the ophthalmologist to reveal the
      pathogenesis of diabetic retinopathy and explore the protective effect of
      erythropoietin on retinal cells of diabetic rats. It also highlights the
      potential of molecular spectral imaging technology to provide more effective and
      reliable diagnostic criteria in pathology.

PMID- 20030978
TI  - The use of attenuated total reflection infrared spectroscopy to study the
      intercalation of molten polymer into layered silicates in real time.
AB  - The intercalation of molten polymer into layered silicates (nanoclays) is a
      critical step in the fabrication of commercial polymer nanocomposite products, so
      it is therefore very important to understand the process of intercalation and
      exfoliation, as well as to properly characterize the final state achieved.
      Following on our recent work demonstrating the potential of transmission infrared
      spectroscopy for this purpose, we show in this work how the attenuated total
      reflection technique can be used to study the intercalation process in real time.
      Although various aspects of the Si-O stretching bands near 1150-950 cm(-1) are
      sensitive to the intercalation, the most sensitive parameter is the relative
      intensity of the out-of-plane band near 1077 cm(-1). A method based on the second
      derivative of the spectrum has been developed to quantify this aspect. The
      application of this approach is described in detail and examples are given
      involving different polymers.

PMID- 20030979
TI  - In situ orientation studies of a poly(3-hydroxybutyrate)/poly(epsilon
      caprolactone) blend by rheo-optical fourier transform infrared spectroscopy and
      two-dimensional correlation spectroscopic analysis.
AB  - In the present study, the orientation of a poly(3-hydroxybutyrate)
      (PHB)/poly(epsilon-caprolactone) (PCL) blend was monitored during uniaxial
      elongation by rheo-optical Fourier transform infrared (FT-IR) spectroscopy and
      analyzed by generalized two-dimensional correlation spectroscopy (2D-COS). The
      dichroism of the delta(CH(2)) absorption bands of PHB and PCL was employed to
      determine the polymer chain orientation in the PHB/PCL blend during the
      elongation up to 267% strain. From the PHB and PCL specific orientation functions
      it was derived that the PCL chains orient into the drawing direction while the
      PHB chains orient predominantly perpendicular to the applied strain. To extract
      more detailed information about the polymer orientation during uniaxial
      elongation, 2D-COS analysis was employed for the dichroic difference of the
      polarization spectra recorded during the drawing process. In the corresponding
      synchronous and asynchronous 2D correlation plots, absorption bands
      characteristic of the crystalline and amorphous regions of PHB and PCL were
      separated. Furthermore, the 2D-COS analysis revealed that during the mechanical
      treatment the PCL domains orient before the PHB domains.

PMID- 20030980
TI  - Hydrogen bonding interactions in three 2-mercaptoethanol systems: an excess
      infrared spectroscopic study.
AB  - The hydrogen bonding properties of a representative molecule, 2-mercaptoethanol
      (ME), of which two functional groups OH and SH are believed to interact
      competitively or selectively with proton-accepting molecules, have been studied.
      Three binary systems, namely ME-CCl(4), ME-dimethyl sulfoxide (DMSO), and ME
      acetone, were investigated with excess infrared absorption spectroscopy. It is
      found that when DMSO or acetone is added into ME, they preferentially form
      hydrogen bonds with OH, and the hydrogen bonds in the ME-DMSO system are stronger
      than those in the ME-acetone system. When CCl(4) is added into ME, the weak
      hydrogen bonds involving the SH group are broken preferentially with increasing
      CCl(4) concentration. The dissociation process of ME in the inert diluent CCl(4)
      over the entire concentration range has been discussed in detail. In the very low
      concentration range of CCl(4), the highly hydrogen bonded ME multimers mainly
      break into medium-sized aggregates. The amount of the trimers and dimers first
      increases and then, at x(CCl(4)) = 0.77, begins to decrease. These results
      suggest that excess infrared spectroscopy can provide detailed molecular pictures
      in liquid solutions containing complex hydrogen bonding interactions. It can also
      help to locate individual peak positions in the deconvolution of overlapped
      absorption bands.

PMID- 20030981
TI  - Procedure for automated background correction in flow systems with infrared
      spectroscopic detection and changing liquid-phase composition.
AB  - This paper describes a partial least squares (PLS) based automatic procedure to
      correct for changes in the spectral contribution of the solvent or solvent
      mixtures from solute spectra recorded in these solvents. The procedure was
      developed for successful on-line Fourier transform infrared (FT-IR) detection in
      gradient high-performance liquid chromatography (HPLC) separations. It requires a
      reference FT-IR data set containing all possible combinations of the expected
      variation in solvent composition. Furthermore, a spectral region (A) in these
      spectra is required where the solvents show absorption but the analytes do not.
      This is the case for the system ACN:H(2)O, an often-applied solvent mixture in
      gradient HPLC, in the spectral region from 2300-2400 cm(-1). By focusing on (A)
      the developed numerical method selects an appropriate background spectrum from
      the reference data set, which is then subtracted from the analyte spectra. The
      method was programmed in Matlab and tested on different isocratic and gradient on
      line reversed phase liquid chromatography-Fourier transform infrared spectrometry
      (LC-FT-IR) data sets. This work describes a successful method to perform eluent
      correction in on-line coupling of FT-IR spectrometry with gradient LC.

PMID- 20030982
TI  - An iterative algorithm for background removal in spectroscopy by wavelet
      transforms.
AB  - Wavelet transforms are an extremely powerful tool when it comes to processing
      signals that have very "low frequency" components or non-periodic events. Our
      particular interest here is in the ability of wavelet transforms to remove
      backgrounds of spectroscopic signals. We will discuss the case of surface
      enhanced Raman spectroscopy (SERS) for illustration, but the situation it depicts
      is widespread throughout a myriad of different types of spectroscopies (IR, NMR,
      etc.). We outline a purpose-built algorithm that we have developed to perform an
      iterative wavelet transform. In this algorithm, the effect of the signal peaks
      above the background is reduced after each iteration until the fit converges
      close to the real background. Experimental examples of two different SERS
      applications are given: one involving broad backgrounds (that do not vary much
      among spectra), and another that involves single molecule SERS (SM-SERS)
      measurements with narrower (and varying) backgrounds. In both cases, we will show
      that wavelet transforms can be used to fit the background with a great deal of
      accuracy, thus providing the framework for automatic background removal of large
      sets of data (typically obtained in time-series or spatial mappings). A
      MATLAB((R)) based application that utilizes the iterative algorithm developed
      here is freely available to download from
      http://www.victoria.ac.nz/raman/publis/codes/cobra.aspx.

PMID- 20030983
TI  - The beta-spherulite morphology of isotactic polypropylene investigated by Raman
      spectroscopy.
AB  - Raman spectroscopy is used to investigate the alpha- and beta-crystalline
      polymorphs of isotactic polypropylene. Raman spectra of the polymorphs show some
      minor differences, in particular the wavenumber shifting of certain scattering
      bands, which reflect the environment of an isolated macromolecular chain within
      the packing unit cell of the different crystal forms. For example, the shifting
      of the 842 cm(-1) scattering band, which is the most susceptible band to cause
      intermolecular interactions, is used to generate a structural map of one beta
      spherulite among alpha-spherulites with a well-defined resolution. Anisotropy of
      the crystalline phase orientation within a beta-spherulite is also investigated
      by performing polarized Raman spectroscopy measurements. Differences in the
      polarized spectra are then finely exploited to map the radial lamellae
      orientation distribution within one beta-spherulite.

PMID- 20030984
TI  - Model-based measurements of diffusion of sulfuric acid into water using Raman
      spectroscopy.
AB  - The diffusion of molecular species within a sulfuric acid-water system has been
      monitored by Raman spectroscopy, a thermodynamic-chemical model of the mass
      transport properties of the species has been established, and its parameters
      optimized. It has been shown that the non-ideality of this multicomponent system
      plays a crucial role in its mass transport properties, which have been explained
      in terms of a diffusion model for the molecular species. The individual effective
      diffusion coefficients are not constant (characteristic of ideal systems) but are
      a function of the concentration of the species in solution. The model has been
      conceived in such a way that it can be adapted to any multicomponent mixture when
      the equilibriums among the ions are known. Raman spectroscopy provides the means
      to derive the speciation and concentration of species in multicomponent systems,
      and we have shown that the model-based measurement of the diffusion properties
      using Raman is a robust and accurate technique that allows for measuring the
      individual diffusion coefficients of the species in the mentioned system.

PMID- 20030985
TI  - Cavity enhanced spectroscopy of high-temperature H(2)o in the near-infrared using
      a supercontinuum light source.
AB  - In this paper we demonstrate how broadband cavity enhanced absorption
      spectroscopy (CEAS) with supercontinuum (SC) radiation in the near-infrared
      spectral range can be used as a sensitive, multiplexed, and simple tool to probe
      gas-phase species in high-temperature environments. Near-infrared SC radiation is
      generated by pumping a standard single-mode fiber with a picosecond fiber laser.
      Standard low reflectivity mirrors are used for the cavity and an optical spectrum
      analyzer is used for the detection of gas-phase species in combustion. The method
      is demonstrated by measuring flame generated H(2)O in the 1500 to 1550 nm region
      and room-temperature CO(2) between 1520 nm and 1660 nm. The broadband nature of
      the technique permits hundreds of rotational features to be recorded, giving good
      potential to unravel complex, convoluted spectra. We discuss practical issues
      concerning the implementation of the technique and present a straightforward
      method for calibration of the CEAS system via a cavity ringdown measurement.
      Despite the large spectral variation of SC radiation from pulse to pulse, it is
      shown that SC sources can offer good stability for CEAS where a large number of
      SC pulses are typically averaged.

PMID- 20030986
TI  - Application of small-spot energy dispersive X-ray fluorescence instrumentation in
      phytoremediation activities around metal mines.
AB  - In view of the considerable number of analyses necessary in phytoremediation and
      plant biology studies, it is important that the analytical procedures used for
      elemental determination in plant tissues should be fast and cheap, with simple
      sample preparation, and of adequate accuracy and precision. The aim of the
      present work was focused on the possibilities and drawbacks of a low-cost
      benchtop energy dispersive X-ray fluorescence (EDXRF) instrument to be used as an
      analytical technique for studying the potential use of sunflowers (Helianthus
      annuus) for the phytoremediation of an abandoned Pb/Zn mining area. The
      simplicity and the ability to operate at room temperature and open air conditions
      provides a flexible setup for the rapid analysis of vegetation material without
      complicated previous sample pretreatments. With the help of different collimator
      caps, a modest lateral resolution (from 200 mum to 1 mm) was achieved and it was
      thought to be small enough to study the accumulation of Pb and Zn and its
      distribution between parts of the vegetation specimens (roots, stems, and
      leaves); the limits of detection achieved (0.6 ng for Zn and 3.0 ng for Pb)
      proved to be suitable for the intended purpose. Therefore, obtained data revealed
      that EDXRF spectrometry could be a useful tool to better understand the metal
      uptake, translocation, and tolerance mechanisms in vegetation species related to
      biomonitoring and phytoremediation studies.

PMID- 20030987
TI  - Direct determination of bismuth in steel samples by magnetic drop-in
      electrothermal vaporization inductively coupled plasma atomic emission
      spectrometry.

PMID- 20030988
TI  - What were they drinking? A critical study of the radium ore revigator.

PMID- 20030989
TI  - Effect of hydrogen bonding on the amide II band of model disubstituted urea
      compounds.

PMID- 20030990
TI  - Visceral leishmaniasis in Aba-Roba, south-western Ethiopia: prevalence and
      incidence of active and subclinical infections.
AB  - Between August 1997 and February 2005, a prospective study of human visceral
      leishmaniasis (VL) was undertaken in two villages in the Konso district of south
      western Ethiopia, to provide epidemiological indices of subclinical infection and
      active VL. Six cross-sectional surveys at 6-month intervals (ending in August
      2000) were complemented by a single survey in February 2005. The prevalences and
      incidences of leishmanial infection and active VL, which were determined using
      leishmanin skin tests (LST), direct agglutination tests (DAT) and parasitological
      diagnosis, varied spatio-temporally and by age and gender. At baseline, when 1339
      individuals were investigated, the overall prevalences of LST positivity, DAT
      positivity and active VL among the 1232 subjects who had not been treated
      previously were 30.0%, 5.4% and 0.49%, respectively. During the study, <10% of
      the subjects found DAT-positive at baseline progressed to active VL (with a mean
      of about nine cases of subclinical infection for every one of active VL). The
      median age of an incident VL case was 10.5 years. The highest rates of LST
      conversion occurred among the subjects aged 5-25 years. A subject who became LST
      positive during the study was much less likely to develop active VL than the
      other subjects.

PMID- 20030991
TI  - Lymphocyte phenotyping, using cluster-of-differentiation (CD) markers, in young
      Iraqi children with visceral leishmaniasis.
AB  - The lymphocytic phenotypes involved in the pathogenesis of visceral leishmaniasis
      (VL) in Iraqi children have recently been investigated, in a study based on
      cluster-of-differentiation (CD) markers. Each case of VL investigated was
      confirmed parasitologically by the observation of amastigotes in a bone-marrow
      smear. Compared with the values for the healthy children used as controls, a
      lymphocyte from an untreated VL case was significantly less likely to be CD3+ or
      CD4+, significantly more likely to be CD8+, and more (but not significantly more)
      likely to be CD22+. The untreated cases also had significantly lower CD4+/CD8+
      ratios than the controls. Among the untreated cases, gender and age had no
      apparent effect on any of these variables. After 28 days of treatment with sodium
      stibogluconate, there was a trend towards normalization in the lymphocytic
      phenotypes of the VL cases, with significant increases in the CD4+/CD8+ ratios
      and the percentages of lymphocytes that were CD3+ or CD4+, and a significant
      decrease in the percentages of lymphocytes that were CD22+.

PMID- 20030992
TI  - Increase in the prevalence of canine leishmaniasis in urban Algiers (Algeria)
      following the 2003 earthquake.
AB  - Between 2005 and 2008, a serological survey for leishmanial infection was
      conducted among dogs from urban and peri-urban Algiers, with the focus on the
      new, densely populated areas that were built after the 2003 earthquake. Serum
      samples were collected from 1810 animals and tested for the presence of
      leishmanial antibodies by IFAT, ELISA and western blotting. The overall
      seroprevalence recorded was 25.1%. Of the seropositive dogs, 58.8% showed no
      clinical signs of the disease, 25.8% had a few, minor signs and the remaining
      15.4% showed more severe illness. The major clinical signs of infection were
      weight loss, skin lesions and lymphadenopathy. Although seropositive dogs were
      found in all of the boroughs (dairas) of Algiers, seroprevalences were highest in
      the western part of the city (i.e. in the boroughs of Bouzareah, Cheraga and
      Zeralda), ranging from 23.0% to 44.5%. Statistical analysis showed a relationship
      between seropositivity for leishmanial infection and the dog's age and lifestyle
      (i.e. whether the dog lived outside and/or in areas with dense vegetation). Only
      two zymodemes were identified amongst the 50 isolates investigated: MON-1 (88%)
      and MON-281 (12%). The latter zymodeme has not been previously found in Algeria,
      sandflies or dogs.

PMID- 20030993
TI  - Antibody and cytokine responses in BALB/c mice immunized with the
      excreted/secreted proteins of Giardia intestinalis: the role of cysteine
      proteases.
AB  - The mechanisms involved in the induction of the immune response in humans or
      experimental hosts infected with Giardia intestinalis are not well understood.
      The results of previous studies indicate that the parasite induces a mixed
      Th1/Th2 response and that, in experimentally infected mice, the parasite's
      excreted/secreted (E/S) proteins contain cysteine proteases that are recognised
      by the murine immune system. In the present study, the possible effects of the
      E/S proteases of G. intestinalis on the host's humoral and cellular immune
      responses were investigated in BALB/c mice immunized with the parasite's E/S
      proteins. High titres of specific IgG(1), IgG(2a) and IgE antibodies were
      detected after immunization with native E/S proteins. Spleen cells stimulated
      with such proteins in vitro showed a significant antigen-specific proliferative
      response accompanied by the production of high concentrations of interleukin-4
      (IL-4), interleukin-5 (IL-5) and interleukin-10 (IL-10) but little secretion of
      interferon-gamma (IFN-gamma). When, before use, the proteases in the E/S proteins
      were inhibited, by heat treatment or the addition of E-64, they elicited much
      lower titres of specific IgG(1) and IgE in mice while, in splenocytes in vitro,
      they triggered much lower production of IL-4, IL-5 and IL-10 and reduced antigen
      specific proliferation. Since E-64 only inhibits cysteine proteases, these
      results indicate that the excreted/secreted cysteine proteases of G. intestinalis
      may be involved in the induction and regulation of a specific immune response in
      the infected host.

PMID- 20030994
TI  - Hypomagnesaemia in the first 10 days of severe leptospirosis.
AB  - Magnesium imbalance in leptospirosis has, for the most part, been neglected by
      the medical and leptospirosis communities. In a recent, retrospective study,
      serum concentrations of magnesium were followed in 15 patients with severe
      leptospirosis. The results revealed that 14 of the 15 patients developed
      hypomagnesaemia at some time during the first 10 days of their illness. In
      severely ill patients, such magnesium deficiency can worsen clinical outcome.
      Magnesium concentrations may affect a number of organ systems and mental status.
      Since altered mental status in leptospirosis is a poor prognostic indicator, it
      is suggested that serum concentrations of magnesium be monitored closely in
      patients with leptospirosis. Any hypomagnesaemia can then be treated promptly, in
      an effort to reduce the morbidity and mortality attributable to the disease.

PMID- 20030995
TI  - Risk factors associated with the seroprevalence of leptospirosis, amongst at-risk
      groups in and around Tanga city, Tanzania.
AB  - The epidemiological status of human leptospirosis in Tanzania has not been well
      defined because of a general lack of awareness of the disease and difficulties in
      its diagnosis. A cross-sectional seroprevalence study, using the microscopic
      agglutination test with a threshold titre of 1 : 160, was therefore conducted,
      among various occupational groups from Tanga city, in November 2005. Of the 199
      subjects investigated, 30 (15.1%) were found to have antibodies that reacted with
      antigens from at least one of the six Leptospira interrogans serovars used in the
      agglutination test. Of the seropositive samples, 36.6% were positive for serovar
      Icterohaemorrhagiae, 30.0% for Bataviae, 20.0% for Hardjo, 6.6% for Tarrassovi,
      3.3% for Ballum and 3.3% for Pomona. Amongst the occupational groups examined,
      livestock farmers, veterinary/meat inspectors and abattoir workers appeared to be
      most at risk, with seroprevalences of 19.4%, 18.1% and 17.1%, respectively.
      Subjects who reported that they milked cows were significantly more likely to be
      found seropositive for Leptospira infection than the other subjects (odds
      ratio=3.44; P<0.001). These findings indicate that a significant proportion of
      the population of Tanga city is being exposed to pathogenic Leptospira. Public
      health interventions against leptospirosis will need to target not only the
      occupational groups considered to be at high risk of infection but also the
      general population at large.

PMID- 20030996
TI  - Molecular and clinical evidence of Ehrlichia chaffeensis infection in Cameroonian
      patients with undifferentiated febrile illness.
AB  - In the U.S.A., human monocytotropic ehrlichiosis (HME) caused by Ehrlichia
      chaffeensis is an emerging tick-transmitted zoonosis. In Cameroon, where E.
      canis, E. chaffeensis and E. ewingii have recently been detected in dogs and/or
      ticks (Rhipicephalus sanguineus), the potential exists for human infections.
      Patients from the coastal region of Cameroon who had acute fevers of unknown
      aetiology were therefore checked for ehrlichial infection, using a real-time PCR
      that amplifies part of a genus-specific gene (dsb) that codes for a disulphide
      bond formation protein. Ehrlichial blood was detected in the peripheral blood
      from 12 (10%) of the 118 patients investigated by PCR. When the 12 amplicons from
      the positive cases were sequenced, they were found to be identical to each other
      and to the corresponding dsb sequence of an Arkansas strain of E. chaffeensis.
      The 12 patients who were PCR-positive for E. chaffeensis suffered from fever
      (100%), headache (67%), myalgia (42%), arthralgia (58%), pulmonary involvement
      (17%) and/or a diffuse rash (17%).

PMID- 20030997
TI  - Post-kala-azar dermal leishmaniasis (PKDL) developing after treatment of visceral
      leishmaniasis with amphotericin B and miltefosine.

PMID- 20030998
TI  - Seroprevalence of Toxoplasma gondii infection among children in Swaziland,
      southern Africa.

PMID- 20030999
TI  - Isolated nasolabial hydatid cyst: an unusual location.

PMID- 20031000
TI  - High prevalence of Schistosoma haematobium infection in Gereida Camp, in southern
      Darfur, Sudan.

PMID- 20031001
TI  - Schistosomiasis in the North region of Cameroon: unexplained decrease in
      prevalence among schoolchildren between 1986 and 2008-2009.

PMID- 20031002
TI  - The Obama dilemma: allergic rhinitis (animal dander allergy)-the great burden of
      illness.
AB  - Allergic rhinitis is one of the most common chronic diseases with over 600
      million people affected worldwide. More than 200 million of them also suffer from
      concomitant asthma. Allergic rhinitis is generally under-diagnosed and under
      treated. A significant burden of allergic rhinitis is due to pet allergies. In
      2008 two major evidence-based documents on the management of allergic rhinitis
      were published, namely the US Rhinitis Practice Parameters and the ARIA/WHO
      Guidelines that stress the burden of allergic rhinitis due to animal allergens
      and the comorbidities of allergic rhinitis. We need a new approach targeting
      individual disease control in rhinitis due to animal allergens emphasizing
      avoidance and active treatment. The goals of the avoidance-treatment are to first
      improve patient care by recognizing each individual patient's burden of disease
      and expectations of therapy, and then to target and adjust the appropriate
      therapies to meet these expectations. Achieving these goals will, ultimately,
      help the patient to better self-manage his or her disease, thereby improving
      overall quality of life.

PMID- 20031003
TI  - Pet dander and perennial allergic rhinitis: therapeutic options.
AB  - Pet allergy may now be the most common perennial allergen in the United States
      based on recent skin-prick testing data. This trend corresponds with the rise
      (from 56 to 63%) in U.S. households having indoor pets over the past 10 years.
      Furthermore small, suspended, particulate animal allergens may be found in 90% of
      all homes and most public indoor areas. Although the most important cat and dog
      allergens are Fel d 1 and Can f 1, respectively, there are five well-described
      allergens for both cats and dogs. The effects of early life domestic pet and
      endotoxin exposure and subsequent clinical sensitivity remain controversial.
      Given that only the rare pet-allergic patient is willing to give away his/her
      pet, it is important to take an evidence-based approach to environmental control.
      Unfortunately, the benefits from changes in the environment that have been shown
      in research studies relate more to a reduction of allergens than symptoms. The
      pharmacotherapy for pet allergy will vary based on whether this is episodic or
      perennial allergic rhinitis (PAR) and on the severity of the symptoms. A stepwise
      approach for management, using both mono- and combination therapy, is proposed.
      Allergen immunotherapy, the only disease-modifying treatment available, may be
      the best therapeutic recommendation for patients with moderate to severe pet
      induced PAR.

PMID- 20031004
TI  - Antihistamines treatment for allergic rhinitis: different routes, different
      mechanisms?
AB  - Antihistamines have been used in the treatment of rhinitis since ancient times.
      Antihistamines can be used via oral or topical route for the treatment of
      allergic rhinitis, as well as nonallergic forms of rhinitis. The topical
      formulation of medications is the preferred treatment route used for many
      diseases. This article will investigate the differences in the route of
      antihistamines in the treatment of allergic rhinitis. A review of the literature
      was performed to investigate the differences between the use of oral and topical
      antihistamines in the treatment of allergic rhinitis. Antihistamines inhibit the
      mediators of inflammation that worsen the symptoms of allergic rhinitis.
      Intranasal and oral antihistamines are important options in the therapy of
      allergic rhinitis, and topical use may result in unexpected benefits to patients
      with allergic rhinitis.

PMID- 20031005
TI  - Antihistamine treatment for allergic rhinitis: different routes, different
      outcomes?
AB  - Allergic rhinitis is one of the most common chronic disorders in the United
      States, causing patients significant discomfort and interfering with quality of
      life and functioning. Histamine is the primary mediator in the development of
      allergic rhinitis symptoms and is a primary therapeutic target. Guidelines, both
      in the United States and globally, recommend antihistamines as first-line therapy
      of allergic rhinitis. This article discusses the outcomes associated with
      intranasal versus oral administration of antihistamines. Both oral and intranasal
      antihistamines are approved for the first-line treatment of allergic rhinitis and
      both formulations result in a reduction in symptoms and an improvement in quality
      of life. Intranasal agents may be preferred in patients in whom nasal congestion
      is particularly bothersome or in cases where a more rapid onset of action is
      desired. Oral agents would be a better choice in young children (especially
      children who are at risk of developing asthma), in cases of poor medication
      compliance, and in patients who are bothered most by histamine-associated
      symptoms, such as itching or red and watery eyes. Both oral and intranasal
      antihistamines are safe and well tolerated and meet the needs of patients with
      allergic rhinitis, especially those with mild to moderate disease.

PMID- 20031006
TI  - Establishing the onset of action of intranasal corticosteroids: is there an ideal
      study design?
AB  - Intranasal corticosteroids (INs) are considered the most effective pharmaceutical
      treatments for nasal allergic rhinitis (AR) symptoms and are recommended as first
      line therapy for moderate-to-severe symptoms. United States Food and Drug
      Administration (FDA) guidelines for clinical development of drug products for AR
      describe three study types used to determine medication onset of action: (1)
      standard phase 3 efficacy studies, (2) park-setting studies, and (3)
      environmental exposure chamber studies. This study was designed to review the
      U.S. FDA guidelines and discuss published studies of each type examining INS
      onset of action. Medline searches were conducted using the terms "onset of
      action" and each of the following: "beclomethasone," "budesonide," "ciclesonide,"
      "fluticasone furoate," "fluticasone propionate," "mometasone furoate," and
      "triamcinolone." Studies included in the analysis were of subjects with seasonal
      or perennial AR; were double-blind, placebo-controlled, and randomized; and
      reported onset-of-action data. Published studies of all three types describing
      INS onset of action vary widely in compliance with guideline recommendations and
      in the calculated onset of these medications. The usefulness of the study types
      used to assess AR therapies-standard efficacy, park setting, and environmental
      exposure chamber-can be assessed based on each study's ability to reproduce real
      world settings, limit variability of allergen exposure, limit variation in study
      design, and ensure patient adherence to study drug. Studies conducted in an
      environmental exposure chamber to determine onset of action for INSs may be of
      superior design because outcomes are significantly less variable and more
      reproducible than those of other types.

PMID- 20031007
TI  - Safety and efficacy of olopatadine hydrochloride nasal spray 0.6% in pediatric
      subjects with allergic rhinitis.
AB  - Olopatadine (OLO) nasal spray 0.6% is indicated for treatment of seasonal
      allergic rhinitis (SAR) in subjects > or = 12 years of age. This study was
      designed to present the results of two studies that evaluated the efficacy,
      safety, and pharmacokinetics (PK) of OLO in children with allergic rhinitis (AR).
      These were multicenter, double-blind, randomized, parallel-group studies in
      subjects 6 to <12 years of age (study 1) and 2 to <6 years of age (study 2) with
      SAR (study 1) or AR (study 2). In study 1, nasal and ocular symptoms were scored
      for efficacy, and study 2 included PK analyses. In both studies, subjects were
      evaluated based on physical/nasal examinations and adverse events (AEs). Overall,
      1188 subjects (study 1) and 132 subjects (study 2) were randomized, respectively.
      OLO (1 or 2 sprays/nostril, b.i.d.) was superior to vehicle in the percent
      decrease in reflective total nasal symptom scores (p < or = 0.0120). OLO 1
      spray/nostril b.i.d. was also superior to vehicle in the percent decreases in
      reflective total ocular symptom scores (p < or = 0.0084), change from baseline in
      Pediatric Rhinoconjunctivitis Quality-of-Life Questionnaire scores (p < or =
      0.0377), Caregiver Treatment Satisfaction Questionnaire scores (p < or = 0.0450),
      and proportions of subjects reporting improvements in Subject Global Assessments
      (p = 0.0035). The most frequently reported treatment-related events in the OLO
      group were bad/bitter taste and epistaxis. In subjects 6 to <12 years of age, OLO
      was superior to vehicle in the treatment of SAR. In subjects 2 to <12 years of
      age, OLO had an overall low rate of AEs and low systemic exposure.

PMID- 20031008
TI  - Effect of evaporative coolers on skin test reactivity to dust mites and molds in
      a desert environment.
AB  - Dust mites and molds are usually not found in arid environments and have a lower
      prevalence in desert areas. Evaporative (swamp) coolers increase indoor humidity
      significantly. The purpose of this study is to determine whether evaporative
      coolers affect the skin test rate to dust mites and molds in patients. Patients
      with asthma or allergic rhinitis who were undergoing skin testing for molds,
      indoor allergens, grasses, weeds, and trees were asked about presence of central,
      window, and evaporative cooler air conditioning in their home. All were tested
      using the prick technique with controls. One hundred ninety patients between 1
      and 42 years (mean, 5.4 years) were evaluated. Fifty-nine (31%) had an
      evaporative cooler in their home. Twenty-five (42%) of those with evaporative
      coolers had a positive skin test to at least one mold compared with 26 (19%)
      without coolers (chi-square, 10.5; p = 0.001). Twenty (34%) of those with
      evaporative coolers had a positive skin test to dust mites compared with 23
      (17.5%) without coolers (chi-square, 6.2; p = 0.013). Children < or = 6 years of
      age had the greatest skin test prevalence (chi-square, 4.3; p = 0.03). In the
      desert, children in homes using evaporative coolers are significantly more likely
      to have positive skin tests to molds or mites. This appears to be because of
      humidity caused by these devices. Patients with asthma in homes with evaporative
      coolers should be counseled about the risk for mold and dust-mite allergy.
      Humidity monitoring, cooler maintenance, and filter changes should be discussed.

PMID- 20031009
TI  - Cost and resource utilization comparisons of second-generation antihistamines vs.
      montelukast for allergic rhinitis treatment.
AB  - This study evaluates the costs and utilization burden associated with oral,
      branded second-generation antihistamines (BSGAs) compared with montelukast (MTLK)
      as first-choice treatment in newly diagnosed allergic rhinitis (AR) patients
      without asthma. We compared annual medical costs of illness and utilization
      changes from 1 year before index AR diagnosis to 1 year after for continuously
      enrolled AR patients initiating therapy with BSGA or MTLK. Multivariate
      regressions for each outcome variable adjusted for confounders including age,
      sex, geographic region, Charlson Comorbidity Index, RxRisk Score, 18 comorbidity
      groups, and payer type. Treatment selection bias was evaluated by propensity
      score with all covariates plus instrumental variables including physician type
      and likelihood of prescribing MTLK versus BSGA. Insurance claims data for the
      years 2003-2007 included AR patients in all regions of the United States. The
      final sample included 13,703 AR patients taking BSGAs (84%) or MTLK (16%). After
      confounder adjustment, MTLK patients experienced higher total medical costs
      ($1,542 versus $989), drug costs ($714 versus $477), AR drug costs ($474 versus
      $298), and outpatient visit costs ($480 versus $277) than BSGA patients (all
      values of p < 0.025). MTLK patients experienced higher total visits (0.96), AR
      outpatient visits (0.71), and comorbidity visits (0.12) than BSGA patients (all
      values of p < 0.01). MTLK patients were more likely to add additional AR therapy
      medications (MTLK, 43.2%; BSGA, 31.6%; p < 0.01). New AR patients prescribed MTLK
      as first-line medication therapy have higher medical costs and resource
      utilization than those prescribed first-line oral BSGAs. These differences
      persisted after adjustment for patient fixed effects, available confounders, and
      treatment propensity scores.

PMID- 20031010
TI  - Sesame allergy: role of specific IgE and skin-prick testing in predicting food
      challenge results.
AB  - There are conflicting data regarding the diagnostic value of sesame-specific IgE
      and sesame skin test. Currently, there are no established thresholds that predict
      clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin
      prick test (SPT) results with oral challenge outcomes in children suspected of
      having a sesame food allergy. We conducted a retrospective chart review of
      children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food
      challenge from January 2004 to August 2008 at Children's Hospital Boston and
      affiliated allergy clinics. Food challenges were conducted in cases of
      questionable clinical history or a negative ImmunoCAP and/or negative SPT despite
      a convincing history. Thirty-three oral sesame challenges were conducted. Of the
      33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame
      specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal
      size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic
      (ROC) curve analysis for sesame-specific IgE revealed an area under the curve
      (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To
      our knowledge, this study represents the largest number of sesame challenges
      performed to evaluate the diagnostic value of both sesame-specific IgE and SPT.
      Based on our sample, both tests are not good predictors of true sesame allergy as
      determined by an oral challenge. We were unable to establish a threshold with a
      95% positive predictive value for both sesame-specific IgE and SPT.

PMID- 20031011
TI  - Quantitative immunoglobulins in adulthood.
AB  - Although age-related changes in serum immunoglobulins are well described in
      childhood, alterations in immunoglobulins in the elderly are less well described
      and published. This study was designed to better define expected immunoglobulin
      ranges and differences in adults of differing decades of life. Sera from 404
      patients, aged 20-89 years old were analyzed for quantitative immunoglobulin G
      (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). The patients with
      diagnoses or medications known to affect immunoglobulin levels were identified
      while blinded to their immunoglobulin levels. A two-factor ANOVA was performed
      using decade of life and gender on both the entire sample population as well as
      the subset without any disease or medication expected to alter immunoglobulin
      levels. A literature review was also performed on all English language articles
      evaluating quantitative immunoglobulin levels in adults >60 years old. For the
      entire population, IgM was found to be higher in women when compared with men (p
      < 0.001) and lower in the oldest sample population compared with the youngest
      population (p < 0.001). For the population without diseases known to affect
      immunoglobulin levels, the differences in IgM with gender and age were maintained
      (p < or = 0.001) and IgA levels were generally higher in the older population
      when compared with the younger population (p = 0.009). Elderly patients without
      disease known to affect immunoglobulin levels have higher serum IgA levels and
      lower serum IgM levels. Women have higher IgM levels than men throughout life.
      IgG levels are not significantly altered in an older population.

PMID- 20031012
TI  - A 6-year-old boy with fever and eosinophilia.
AB  - Tissue and blood eosinophilia can be associated with a variety of infectious,
      allergic, and systemic diseases. Eosinophilia can range from mild and clinically
      inconsequential levels to high-grade eosinophilia with severe and potentially
      fatal consequences. Because of its ability to degranulate and produce cytotoxic
      mediators such as major basic protein and eosinophil peroxidase the eosinophil
      has the potential to cause considerable tissue damage, including potentially
      fatal conditions such as endomyocardial fibrosis. The most common infectious
      cause of eosinophilia worldwide is the parasitic helminth; fungal infection as a
      cause of eosinophilia is rarer, but must also be considered in the differential
      diagnosis. In this article we describe a unique case of reactive eosinophilia.

PMID- 20031013
TI  - Egg allergy and influenza vaccination.
AB  - Many egg-allergic patients are unnecessarily restricted from receiving the
      influenza vaccine. Patients with suspected egg allergy who require seasonal or
      H1N1 influenza vaccination can pose a significant challenge and should be
      appropriately evaluated by an allergist/immunologist. In most cases, if the
      benefits are felt to outweigh the risks, precautionary measures are available
      that can enhance safe vaccine administration. A case of influenza vaccine
      management in a child with egg allergy is presented. Clinical characteristics,
      diagnostic testing, case management, and natural history are reviewed. Clinical
      Pearls and Pitfalls include: (1) Batch-to-batch variability of egg content in
      extant influenza vaccines necessitates an informed and cautious approach to
      vaccination of an egg-allergic individual. (2) Due to denaturation of some egg
      proteins through heating, tolerance of "baked egg" products may not predict
      tolerance of "native egg" proteins present in the influenza vaccine. (3)
      Intradermal skin testing with influenza vaccine diluted 1:10 may be irritating to
      the skin and result in false positive results. (4) If skin test to the vaccine is
      positive, vaccination may still be cautiously administered, if necessary, in a
      graded-dose protocol, as presented herein. (5) Most patients with egg allergy are
      likely to develop egg tolerance by late childhood.

PMID- 20031014
TI  - What's on the mind of IVF consumers?
AB  - During economic downturns demographers note that birth rates often decline as
      couples are more concerned with job security than providing for an additional
      child. The effects of economic conditions are likely to be amplified in infertile
      couples because there is often the need to pay for treatment. To try and
      understand changes in public interest in IVF over time, this study explored
      publicly available data (Google Insights) that reports changes in internet search
      activity relative to baseline volumes for search queries entered into Google
      search engines. Using the USA and the UK as case studies, it was observed that
      interest in internet searches using the term 'IVF' relative to searches within
      the infertility category remained relatively unchanged in the USA, with a small
      decrease observed in the UK. Internet searches using the combined terms 'IVF
      cost' and 'cost of IVF' have increased over the past 2 years relative to the
      infertility category. Additionally, inclusion of the term 'cost' appears
      concentrated in US states without insurance mandates compared with states with
      mandated insurance coverage. The extent to which Google internet search queries
      reflect public interest, and more importantly interest from infertile couples, is
      difficult to know for certain; however, there appears to be increased interest in
      the cost of treatment.

PMID- 20031015
TI  - Phosphatidylserine translocation in human spermatozoa from impaired
      spermatogenesis.
AB  - The aim of the present study was to evaluate phosphatidylserine translocation in
      specific patient groups and compare the rates of apoptosis between ejaculated and
      testicular spermatozoa. Fifty-six patients undergoing infertility treatments were
      included in the present study. Semen samples (n = 37) were obtained from cases
      with normozoospermia (n = 9) and abnormal semen parameters (n = 28). Testicular
      biopsy was performed in 19 patients, eight with obstructive and six with non
      obstructive (hypospermatogenesis) azoospermia, and in five patients without
      azoospermia (anejaculation and oligozoospermia). Phosphatidylserine
      externalization was assessed using annexin-V binding and fluorescence microscopy,
      and propidium iodide exclusion tests were used to distinguish live from dead
      cells. In semen, oligoasthenoteratozoospermia showed significantly increased
      rates of sperm apoptosis (60.3 +/- 12.9) than normozoospermia (47.5 +/- 10.2). In
      testis, hypospermatogenesis (63.3 +/- 10.3) and obstructive azoospermia (63.6 +/-
      15.1) showed significantly increased rates of sperm apoptosis than non
      azoospermic patients (49.6 +/- 25.5). Comparisons between semen and testis showed
      that oligozoospermia had significantly higher rates of sperm apoptosis in semen
      (57.9 +/- 11.9) than in testis (29.4 +/- 1.1). The results suggest the presence
      of a post-testicular apoptotic induction factor and the potential beneficial use
      of testicular spermatozoa in clinical treatments.

PMID- 20031016
TI  - Does age at orchidopexy impact on the results of testicular sperm extraction?
AB  - The aim of this study was to evaluate the affect of age at the time of
      orchidopexy on testicular sperm extraction (TESE) results among patients with a
      history of cryptorchidism and azoospermia. This retrospective study compared TESE
      results for couples undergoing IVF treatment, among two groups of patients. Group
      A included patients who underwent orchidopexy at age 10 and younger, and group B
      included patients who had the procedure above the age of 10. A total of 42
      patients were included in the study. Forty patients had bilateral cryptorchidism
      and two had unilateral. The overall rate of sperm recovery was 59.5%. No
      differences were found in the sperm retrieval, fertilization, implantation,
      pregnancy, or live birth rates between the groups. The results suggest that age
      at orchidopexy, either at 10 years of age or younger or above 10 years of age,
      was not a predictive factor for successful TESE. Although bilateral
      cryptorchidism is usually considered a testicular secretory dysfunction, it was
      found that sperm retrieval attempts yielded spermatozoa in almost 60% of patients
      with azoospermia and a history of cryptorchidism.

PMID- 20031017
TI  - Effect of vascular endothelial growth factor on sperm motility and survival.
AB  - Vascular endothelial growth factor (VEGF) and its receptors are present in both
      male and female reproductive systems. In this experimental study, the effect of
      different concentrations of VEGF on sperm motility and survival in vitro was
      investigated. Human spermatozoa, collected from voluntary, proven fertile donors,
      were incubated in sperm washing medium containing different concentrations of
      VEGF (5, 10, 15, 20 ng/ml) for 24 h in a university reproductive endocrinology
      laboratory setting. Assessment of VEGF action on sperm motion characteristics was
      evaluated using a computer-assisted semen analyser. Sperm survival was determined
      by hypo-osmotic swelling and eosin-Y dye tests. VEGF had a positive effect on
      some parameters of sperm motility in a concentration-dependent manner. Maximal
      effect was observed at a concentration of 15 ng/ml; motility, progression,
      straight-line velocity and curvilinear velocity of VEGF-exposed spermatozoa were
      significantly increased (P < 0.05) at this concentration. However, sperm
      viability was not prolonged at any concentration of VEGF as shown by hypo-osmotic
      swelling and eosin-Y dye tests. VEGF may increase some sperm motility parameters,
      but not survival, in a concentration-dependent manner in vitro.

PMID- 20031018
TI  - Live births after management of severe OHSS by GnRH antagonist administration in
      the luteal phase.
AB  - Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian
      stimulation protocols. Currently, no curative therapy exists and the main
      preventive option is cycle cancellation. Gonadotrophin-releasing hormone (GnRH)
      antagonist administration in the luteal phase was recently proposed as a new
      approach for the management of patients with established severe OHSS. Three
      polycystic ovarian syndrome patients undergoing IVF treatment developed severe
      OHSS, diagnosed 6 days after oocyte retrieval. On day 6, the patients underwent
      blastocyst transfer and received GnRH antagonist for 4 days, combined with luteal
      phase support using exogenous oestradiol and progesterone. Two patients had
      successful pregnancies that resulted in births of healthy infants, while one
      patient had a biochemical pregnancy. In all patients, established severe OHSS
      regressed to a moderate form of the syndrome, no pregnancy-induced life
      threatening OHSS was observed, while a short monitoring period was required at an
      outpatient level, avoiding the need for patient hospitalization. This is the
      first report in the literature on GnRH antagonist administration in the luteal
      phase, combined with embryo transfer and exogenous oestradiol and progesterone
      supplementation. This novel treatment was effective in the regression of
      established severe OHSS, and resulted in the birth of healthy infants.

PMID- 20031019
TI  - Pronuclear zygote score following intracytoplasmic injection of hyaluronan-bound
      spermatozoa: a prospective randomized study.
AB  - The aim of this study was to determine whether the early stages of embryo
      development, as assessed by the zygote score (Z-score), could be influenced by
      the injection of spermatozoa that had been preselected on the basis of their
      binding to hyaluronic acid (HA). A total of 407 sibling metaphase II oocytes,
      belonging to 44 different patients, were injected in a prospective randomized
      way, with either hyaluronic acid bound (HA(+) ) or non-bound (HA(-)) spermatozoa.
      The fertilization rate (75-70%), the percentage of the different Z-scores (Z 1:
      22-24%, Z 2: 22-22.5%, Z 3: 44- 45%, Z 4: 12-8.5%), the mean score of the
      transferred embryos (3.76 +/- 1.29, 3.78 +/- 1.1) and the number of embryos at
      the 4-cell stage 45 h after injection (77-76%) were not different between the two
      groups. The ongoing pregnancy rate in this study (>20 weeks of gestation) was
      36.4% per replacement, the implantation rate 28% and the twin pregnancy rate 44%
      (7/16). Although binding to HA did not apparently influence the Z-score, this
      agent continues to be used for the immobilization of spermatozoa prior to
      injection, on the basis that it is a natural product that can easily be
      metabolized by the oocyte via normal biological mechanisms.

PMID- 20031020
TI  - Outcome of ICSI using zona pellucida-bound spermatozoa and conventionally
      selected spermatozoa.
AB  - This study aimed to investigate whether the spermatozoa-zona pellucida binding
      test is able to select spermatozoa with higher fertilization potential and higher
      rate of successful embryo development. This prospective study was performed with
      metaphase II (MII) oocytes retrieved from couples undergoing intracytoplasmic
      sperm injection (ICSI) cycles. For each patient, half of the MII oocytes were
      injected using a routine ICSI method (control group, n = 194) while the other
      half were injected with previously zona pellucida-bound spermatozoa (ZP-binding
      group, n = 194). Fertilization rate, high-quality embryo rate, and embryo
      transfer rate were compared between the groups. No significant difference was
      observed among the groups in the fertilization rate (76.8% versus 77.3% for
      control and ZP-binding groups, respectively). However, an increased percentage of
      high-quality embryos was observed when zona pellucida-bound spermatozoa were
      injected (70.0% versus 83.3% for control and ZP-binding groups, respectively, P =
      0.003). Moreover, when embryo selection was performed while ignoring experimental
      group origin, embryos from the ZP-binding group were more commonly selected for
      transfer (43.6% versus 54.6% for control and ZP-binding groups, respectively, P =
      0.004). These findings suggest that the spermatozoa-zona pellucida binding test
      may be an efficient method to identify the most competent spermatozoa for ICSI.

PMID- 20031021
TI  - Apoptosis in normal ovaries of women with and without endometriosis.
AB  - The aim of this study was to evaluate the factors predisposing to implants of
      endometriotic lesions in normal ovarian cortexes of women with and without
      endometriosis by assessing the expression of pro-apoptotic and anti-apoptotic
      factors and follicular density. Ovarian biopsies were performed during
      laparoscopy in 18 patients with endometrioma and in 10 healthy women. Detection
      of apoptosis was performed with terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labelling assay. p53 and BCL2 proteins were assessed by
      immunohistochemistry. Quantitative real-time polymerase chain reaction was
      performed to evaluate BAX , BAK , BCL2 , BCL-XL , survivin and beta-actin ( ACTB
      ) expression. The p53 protein was positive in a significantly higher number of
      secondary follicles, whereas the B-cell chronic lymphocytic leukaemia/lymphoma 2
      (BCL2) protein was positive in all follicles in unaffected tissue of
      endometriotic women, compared with the controls. Overexpression of the BCL2 and
      survivin genes and a decreased BAX and BAK gene expression were observed in the
      endometriotic group although only the difference in survivin expression was
      significant (P = 0.016). The BCL2 / BAX ratio showed an increased value in the
      ovarian cortex in controls compared with endometriosis patients. In conclusion,
      the reduction of apoptosis in unaffected tissue in women with endometriosis
      suggests that they may be predisposed to develop endometriosis.

PMID- 20031022
TI  - Ongoing pregnancies from early retrieval of prematurely developing antral
      follicles after DHEA supplementation.
AB  - Two patients with severely diminished ovarian reserve who were refractory to
      aggressive ovarian stimulation conceived with oocytes from prematurely developing
      antral follicles after dehydroepiandrosterone supplementation. The first patient
      had 11 and 14.5 mm, and the second patient had 13 mm antral follicles on cycle
      days 2 and 3 respectively. In the first case, no ovarian stimulation was
      performed, while the second case received one dose of gonadotrophins with a
      gonadotrophin-releasing hormone antagonist. Following very early human chorionic
      gonadotrophin (HCG) triggering on cycle day 5, when antral follicles reached 15
      and 18.5 mm in the first case, and 19 mm in the second case, IVF intracytoplasmic
      sperm injection treatment resulted in pregnancies in both cases, which are
      currently ongoing at 35 and 14 weeks of gestation. The results in these patients
      show that pregnancy can be achieved in poor responder patients with prematurely
      developing antral follicles following early HCG triggering based on follicle size
      rather than cycle day, with no or minimal stimulation. Whether DHEA
      supplementation had any impact on the success of these cycles remains to be
      determined.

PMID- 20031023
TI  - Excellent embryo quality obtained from vitrified oocytes.
AB  - Oocyte vitrification has the potential to expand tremendously the reproductive
      options for women desiring fertility preservation. Indeed, the number of
      publications regarding the reliability and efficiency of oocyte vitrification has
      increased exponentially over the past decade. The application of the technique to
      standard reproductive technologies depends on not only oocyte survival, but also
      the developmental potential and clinical outcomes from the resultant embryos. The
      aim of this study, therefore, was to examine the embryo quality obtained from
      vitrified, warmed oocytes in a standard infertility population. The results
      demonstrate that high quality blastocyst development can be expected with
      subsequent excellent obstetric and perinatal outcomes. These data support oocyte
      vitrification as a promising technique for fertility preservation.

PMID- 20031024
TI  - Comparison of methods to determine the assigned value in an external quality
      control programme for embryo evaluation.
AB  - This study set out to establish adequate assigned values for a National External
      Quality Control Programme of embryo evaluation. The results obtained by Spanish
      laboratories in this programme are compared with those of a group of national
      experts in embryo quality. Image-based embryo evaluation consists not only of
      classifying embryos as being of optimal, moderate or poor quality, but also of
      specifying the clinical decision to be taken regarding each embryo (transfer,
      cryopreservation or rejection). The proportion of embryos for which there was a
      high degree of agreement among the experts was 98.3% for embryo classification
      and 93.3% for clinical decision; for the laboratories, the respective values were
      44.2 and 42.5%. With respect to the interobserver agreement among laboratories
      and experts, kappa coefficients were lower than 0.6 both for classification and
      for clinical decision. The experts recommended cryopreservation of a higher
      percentage of embryos classified as poor quality than did the laboratories (28
      versus 4%, P = 0.05). The data obtained show that the agreement among
      laboratories is lower than among experts, and that the concordance among experts
      and laboratories is moderate. Therefore, it is recommended that an assigned value
      from external quality control programmes is established based on the consensus
      values obtained from experts.

PMID- 20031025
TI  - Rapid and powerful decaplex and dodecaplex PGD protocols for Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a common childhood lethal X-linked recessive
      disorder, resulting from deletions, duplications and point mutations in the
      dystrophin gene. Single-cell protocols for preimplantation genetic diagnosis
      (PGD) still remain challenging due to the enormous size of the gene and the high
      risk of intragenic recombination, limitations that often lead to sex
      determination and selection of female embryos. This study describes direct and
      rapid decaplex and dodecaplex polymerase chain reaction protocols enabling the
      analysis of five or seven exons and four microsatellite markers scattered along
      the dystrophin gene, chosen to be located in the two deletion hotspots, and the
      analysis of amelogenin sequences for gender determination. The dodecaplex
      protocol may be applied to most of the couples requesting PGD for DMD in whom the
      female partner is a carrier of a deletion. This generic approach will allow
      prompt response to the PGD referrals by reducing the pre-clinical PGD work-up. It
      was successfully applied in three DMD families, resulting in the birth of a girl
      as well as in a healthy ongoing pregnancy.

PMID- 20031026
TI  - Induction of mesenchymal/epithelial marker expression in human amniotic fluid
      stem cells.
AB  - Although dialysis and transplantation are widely applied therapies for renal
      failure, drawbacks such as morbidity, shortage of compatible organs and high cost
      are limiting factors. Recently, interest has increased in the potential use of
      stem cells for the repair of kidney injury, which has been considered as an
      alternative therapeutic strategy. Due to their high proliferation rates, their
      pluripotent differentiation potential, the finding that they do not induce tumour
      formation and the fact that they do not raise the ethical concerns connected with
      human embryonic stem cells, human amniotic fluid stem cells are considered to be
      a very promising cell source. This study demonstrates that the expression of the
      mesenchymal markers CD29 and CD44, the epithelial markers CD51 and ZO-1 and the
      podocyte markers CD2AP and NPHS2 can be induced in these cells via incubation
      with epidermal growth factor/platelet-derived growth factor BB and fibroblast
      growth factor 4/hepatocyte growth factor, respectively. Since podocytes are
      visceral epithelial cells in the kidneys, which form the essential part of the
      glomerular filtration barrier, these findings warrant further investigation of
      the potential use of human amniotic fluid stem cells for cell-based kidney
      therapies.

PMID- 20031027
TI  - Significance of positive Chlamydia serology in women with normal-looking
      Fallopian tubes.
AB  - Chlamydia trachomatis poses a potential threat to the fertility of women by
      causing tubal damage. Many women with serological evidence of past Chlamydia
      infection have normal tubal appearances on laparoscopic assessment. The aim of
      this study was to assess if serological evidence of past chlamydial infection
      affects the likelihood of conception in women with normal tubes. Infertile
      couples in which the female partner was under the age of 40 years, with normal
      ovulatory function and a male partner with normal sperm function were studied.
      All women had normal tubes as assessed by laparoscopy. Serum Chlamydia antibody
      titres were assayed using the immunofluorescence test. Pregnancy rates were
      related to grouped Chlamydia antibody titres (<64, 64-256 and > or =512). A total
      of 174 women were studied. The cumulative pregnancy rates (SE) according to these
      titres were 45.1% (6.2), 42.6% (9.3), 59.1% (11.8) and the risk ratios (95%
      confidence interval) were 1, 1.59 (0.82-3.07) and 1.04 (0.52-2.08) respectively.
      The differences were not statistically significant. Therefore, in women with
      normal-looking tubes, serological evidence of past chlamydial infection does not
      appear to have an adverse effect on pregnancy rates. These findings suggest that
      laparoscopic findings and not Chlamydia serological titres are the key to
      prognosis.

PMID- 20031028
TI  - Effect of exercise on the reproductive outcome and fetal development of diabetic
      rats.
AB  - The aim of this study was to evaluate the effect of exercise on pregnancy outcome
      in streptozotocin-induced diabetic Wistar rats (n = 11 animals/group). These
      animals were randomly assigned to sedentary (G1) and exercised groups, beginning
      from day 0 (G2) or 7 (G3) to day 20 of pregnancy. The moderate exercise was a
      swimming programme. At day 21 of pregnancy, all rats were anaesthetized and
      killed to obtain pregnancy outcome data. All rats presented glycaemia higher than
      300 mg/dl, regardless of the exercise training. The G3 group showed higher live
      fetus number per implantation site and lower resorption number per implantation
      site compared with the G1 group. The fetal and placental mean weights per litter
      and the total number of ossification sites were significantly lower in the
      exercised groups (P < 0.05). Placental index was lower in the G2 and G3 groups
      compared with the G1 group. The occurrence of skeletal anomalies indicated that
      exercise increased the number of altered fetuses. Thus, moderate exercise
      achieved better outcomes by increasing the number of live births and decreasing
      resorption. However, exercise increased skeletal anomalies and decreased fetal
      and placental weights.

PMID- 20031029
TI  - Serum anti-carbonic anhydrase I and II antibodies and idiopathic recurrent
      pregnancy loss.
AB  - In up to 50% of recurrent pregnancy losses (RPL), the underlying
      pathophysiological mechanisms remain undetermined. Immunological factors may be
      involved. The objective of this study was to compare serum concentrations of
      autoantibodies to carbonic anhydrase (CA) I and II in women with and without RPL.
      Serum anti-CA-I and anti-CA-II concentrations in 29 women with RPL and 39 women
      without RPL on menstrual cycle day 3 were assessed and compared for this
      prospective age-matched controlled study. The mean serum anti-CA-I (0.287 +/-
      0.177 versus 0.184 +/- 0.093, P = 0.003) and anti-CA-II (0.496 +/- 0.240 versus
      0.344 +/- 0.108, P = 0.001) antibody concentrations were significantly higher in
      women with RPL, compared with controls. For serum anti-CA-I, an absorbance higher
      than 0.463 was taken as positive (mean + 3 SD of controls) and was detected in
      four of 29 patients with RPL (13.79%, 0.287 +/- 0.177). For serum anti-CA-II, an
      absorbance higher than 0.668 was taken as positive (mean + 3SD of controls) and
      was detected in seven of 29 patients with RPL (24.14%, 0.496 +/- 0.240). All
      patients with positive anti-CA-I antibody also had positive anti-CA-II antibody.
      Antibodies specifically reactive to CA-I and CA-II were found to be present at a
      higher frequency in the serum of subjects with RPL.

PMID- 20031030
TI  - Differential regulation of Akt phosphorylation in endometriosis.
AB  - Protein kinase B (PKB/Akt), a serine/threonine kinase, regulates the function of
      many cellular proteins involved in apoptosis and proliferation. It was postulated
      that there is a higher Akt activity in endometriosis compared with normal
      endometrium, and that oestrogen may be one of the factors responsible for the
      high Akt activation in endometriotic cells. Phospho-Akt (pAkt) concentrations in
      normal, eutopic and ectopic endometrial tissues were compared by
      immunohistochemistry, and a higher pAkt immunoreactivity was revealed in eutopic
      and ectopic endometrium compared with normal endometrium, in vivo. Higher Akt
      phosphorylation in stromal cells from eutopic endometrium was observed, when
      compared with normal, in vitro (P < 0.05). Akt phosphorylation was rapidly (2-10
      min) stimulated when endometrial stromal cells from normal and endometriosis
      patients were treated with 17 beta-oestradiol. In endometrial stromal cells from
      the endometriosis group, ICI 182,780 (ICI, a specific oestrogen receptor
      antagonist) failed to antagonize the effect of oestradiol when combined with
      oestradiol, and revealed a stimulatory effect on Akt phosphorylation when given
      alone (P < 0.05). In conclusion, since Akt affects cell survival, it is suggested
      that increased Akt phosphorylation may be related to the altered
      apoptosis/proliferation harmony in endometriosis, and therefore Akt may play a
      critical role in the pathogenesis of endometriosis.

PMID- 20031031
TI  - Assisted reproductive technologies in public and private clinics.
AB  - The aim of this study was to analyse the influence of the type of service
      provided by assisted reproduction clinics. The activities, treatment patterns and
      results achieved by assisted reproduction centres in Spain were examined,
      comparing public and private clinics. A retrospective study was carried out using
      the Assisted Reproductive Technology Register of the Spanish Fertility Society
      for 2002-2004. The results showed that 74%, 96% and 99% of IVF/intracytoplasmic
      sperm injection, oocyte donation and preimplantation genetic diagnosis cycles,
      respectively, were carried out in the private sector. Public clinics performed
      proportionally more transfers of three embryos than the private clinics (48.1%
      versus 41.7%). More elective transfers were performed in private clinics.
      Pregnancy rates per cycle started, per puncture and per transfer were
      significantly higher among private than public clinics (29.1%, 32.7% and 35.9%
      versus 25.2%, 28.5% and 32.6%, respectively) (P < 0.05). Implantation rate has
      risen year on year in both types of clinic and was significantly higher (P <
      0.05), every year, among the private clinics. The multiple-pregnancy rate was
      significantly higher among the private clinics (30.8% versus 26.4%) (P < 0.05).
      In conclusion, differences exist between public and private clinics as regards to
      their volume of activity, the range of services offered, clinical practice and
      results achieved.

PMID- 20031032
TI  - Mid-follicular LH supplementation in women aged 35-39 years undergoing ICSI
      cycles: a randomized controlled study.
AB  - This single-centre, randomized, parallel group, comparative study aimed to
      identify potential benefits of mid-follicular recombinant human LH (r-HLH)
      supplementation in women aged 35-39 years undergoing ovarian stimulation for
      intracytoplasmic sperm injection (ICSI). The main endpoint was the number of
      metaphase II oocytes retrieved. After pituitary suppression with a gonadotrophin
      releasing hormone agonist, ovarian stimulation was initiated with recombinant
      human FSH (r-HFSH; 300-450 IU/day). On stimulation day 6, patients were
      randomized to receive r-HFSH alone or r-HFSH + r-HLH (r-HLH 150 IU/day) for the
      remainder of the stimulation period. Final follicular maturation was triggered
      with 250 mug of recombinant human chorionic gonadotrophin. After assessing oocyte
      nuclear maturity, oocyte were fertilized by ICSI and afterwards embryo quality
      was analyzed. Of the 131 women enrolled, 68 were allocated to r-HFSH alone and 63
      to r-HFSH + r-HLH. No significant differences were observed in markers of either
      oocyte or embryo quality or quantity. However, higher rates of implantation and
      live birth per started cycle were observed with r-HLH supplementation than with r
      HFSH alone. Although additional large studies are required to further investigate
      these findings, r-HLH supplementation for women aged 35-39 years undergoing ICSI
      is recommended as it may have a beneficial action on implantation.

PMID- 20031033
TI  - Role of androgens in the treatment of patients with low ovarian response.
AB  - The objective of the current report was to provide a summary of knowledge
      concerning the treatment of women with poor ovarian response with androgens and
      androgen modulating agents. This involved a review of the literature. The
      literature search was performed using PubMed. Information concerning the role of
      androgens and androgen modulating agents in treating women with poor ovarian
      response is limited. The search of the literature yielded five studies and one
      case report concerning the treatment of poor responders with androgens. The
      variations in patient selection, type of androgens employed and the different
      duration of exposure preclude drawing any definite conclusions. Aromatase
      inhibitors block the conversion of androgens to oestrogens, thereby promoting an
      androgen-rich intrafollicular environment. The evidence presented in this review
      suggests a potential beneficial role for the use of aromatase inhibitors in
      treating women who have previously experienced failure of standard IVF protocols.
      The optimal dose and duration of this treatment is yet to be determined. Although
      the results of studies concerning LH supplementation in poor responders are
      conflicting, the latest Cochrane review on the use of recombinant LH for ovarian
      stimulation supports its use in poor responders, based on pooled pregnancy
      estimates.

PMID- 20031035
TI  - Public health threat of new, reemerging, and neglected zoonoses in the
      industrialized world.
AB  - Microbiologic infections acquired from animals, known as zoonoses, pose a risk to
      public health. An estimated 60% of emerging human pathogens are zoonotic. Of
      these pathogens, >71% have wildlife origins. These pathogens can switch hosts by
      acquiring new genetic combinations that have altered pathogenic potential or by
      changes in behavior or socioeconomic, environmental, or ecologic characteristics
      of the hosts. We discuss causal factors that influence the dynamics associated
      with emergence or reemergence of zoonoses, particularly in the industrialized
      world, and highlight selected examples to provide a comprehensive view of their
      range and diversity.

PMID- 20031036
TI  - Laboratory surge response to pandemic (H1N1) 2009 outbreak, New York City
      metropolitan area, USA.
AB  - The North Shore-Long Island Jewish Health System Laboratories serve 15 hospitals
      and affiliated regional physician practices in the New York City metropolitan
      area, with virus testing performed at a central reference laboratory. The
      influenza A pandemic (H1N1) 2009 outbreak began in this area on April 24, 2009,
      and within weeks respiratory virus testing increased 7.5 times. In response,
      laboratory and client service workforces were increased, physical plant build-out
      was completed, testing paradigms were converted from routine screening tests and
      viral culture to a high-capacity molecular assay for respiratory viruses,
      laboratory information system interfaces were built, and same-day epidemiologic
      reports were produced. Daily review by leadership of data from emergency rooms,
      hospital facilities, and the Health System Laboratories enabled real-time
      management of unfolding events. The ability of System laboratories to rapidly
      increase to high-volume comprehensive diagnostics, including influenza A
      subtyping, provided key epidemiologic information for local and state public
      health departments.

PMID- 20031037
TI  - Projecting global occurrence of Cryptococcus gattii.
AB  - Cryptococcus gattii and C. neoformans cause pulmonary and systemic
      cryptococcosis. Recently, C. gattii was recognized as a distinct pathogen of
      humans and animals. We analyzed information from 400 publications (1948-2008) to
      examine whether the fungus occurs globally. Known distribution of C. gattii is
      possibly limited because specialized reagents for differentiation from C.
      neoformans are not readily available and not always used, and environmental
      surveys are patchy. However, autochthonous reports of C. gattii cryptococcosis
      have now been recognized from tropical and temperate regions. An ongoing outbreak
      in western Canada strengthens the case that the range of the pathogen has
      expanded. A few studies have highlighted differences in cryptococcosis between C.
      gattii and C. neoformans. More than 50 tree species have yielded C. gattii
      especially from decayed hollows suggesting a possible ecologic niche. This
      pathogen merits more attention so its environmental occurrence and role in
      cryptococcosis can be accurately determined.

PMID- 20031038
TI  - Epidemiology of travel-associated pandemic (H1N1) 2009 infection in 116 patients,
      Singapore.
AB  - In June 2009, during Singapore's pandemic influenza plan containment phase,
      pandemic (H1N1) 2009 was introduced into the country through imported cases. To
      understand how travel patterns affected the initial outbreak, we examined
      epidemiologic and travel data for the first 116 case-patients admitted to Tan
      Tock Seng Hospital, Singapore, with travel-associated infection. Sixty-one
      percent and 54% of patients, respectively, met US Centers for Disease Control and
      Prevention and World Health Organization temperature criteria for influenza-like
      illness. One fourth of the case-patients traveled after illness onset, and 15%
      became ill while traveling. Regions of exposure for imported infections changed
      rapidly; case-patients initially arrived from North America, followed by
      Australasia and Southeast Asia. Case-patients on longer flights were more likely
      to become ill before arrival; those with shorter flights tended to become ill
      after arrival. Thermal scanners detected fevers in 12% of the arriving case
      patients, resulting in a shorter time to isolation.

PMID- 20031039
TI  - Severe pneumonia associated with pandemic (H1N1) 2009 outbreak, San Luis Potosi,
      Mexico.
AB  - We describe the clinical characteristics and outcomes of adults hospitalized with
      pneumonia during the pandemic (H1N1) 2009 outbreak. Patients admitted to a
      general hospital in San Luis Potosi, Mexico, from April 10 through May 11, 2009,
      suspected to have influenza virus-associated pneumonia were evaluated. We
      identified 50 patients with suspected influenza pneumonia; the presence of
      influenza virus was confirmed in 18: 11 with pandemic (H1N1) 2009 virus, 5 with
      unsubtypeable influenza A virus, 1 with seasonal influenza A virus (H3N2), and 1
      in whom assay results for seasonal and pandemic (H1N1) 2009 viruses were
      positive. Eighteen patients were treated in the intensive care unit, and 10 died.
      During the pandemic (H1N1) 2009 outbreak, severe pneumonia developed in young
      adults who had no identifiable risk factors; early diagnosis and treatment of
      influenza virus infections may have a determinant role in outcome.

PMID- 20031040
TI  - Worldwide dissemination of the blaOXA-23 carbapenemase gene of Acinetobacter
      baumannii.
AB  - To assess dissemination of OXA-23-producing strains of Acinetobacter baumannii,
      we obtained 20 carbapenem-resistant, OXA-23-producing isolates from different
      regions. Their clonal relationship was assessed by pulsed-field gel
      electrophoresis and multilocus sequence typing. We identified 8 sequence types,
      including 4 novel types. All except 2 strains belonged to 2 main European clonal
      lineages. The blaOXA-23 gene was either located on the chromosome or on plasmids
      and associated with 4 genetic structures.

PMID- 20031041
TI  - Recombinant canine coronaviruses in dogs, Europe.
AB  - Coronaviruses of potential recombinant origin with porcine transmissible
      gastroenteritis virus (TGEV), referred to as a new subtype (IIb) of canine
      coronavirus (CCoV), were recently identified in dogs in Europe. To assess the
      distribution of the TGEV-like CCoV subtype, during 2001-2008 we tested fecal
      samples from dogs with gastroenteritis. Of 1,172 samples, 493 (42.06%) were
      positive for CCoV. CCoV-II was found in 218 samples, and CCoV-I and CCoV-II
      genotypes were found in 182. Approximately 20% of the samples with CCoV-II had
      the TGEV-like subtype; detection rates varied according to geographic origin. The
      highest and lowest rates of prevalence for CCoV-II infection were found in
      samples from Hungary and Greece (96.87% and 3.45%, respectively). Sequence and
      phylogenetic analyses showed that the CCoV-IIb strains were related to prototype
      TGEV-like strains in the 5' and the 3' ends of the spike protein gene.

PMID- 20031042
TI  - Ceftiofur resistance in Salmonella enterica serovar Heidelberg from chicken meat
      and humans, Canada.
AB  - The Canadian Integrated Program for Antimicrobial Resistance Surveillance
      describes a strong correlation (r = 0.9, p<0.0001) between ceftiofur-resistant
      Salmonella enterica serovar Heidelberg isolated from retail chicken and incidence
      of ceftiofur-resistant Salmonella serovar Heidelberg infections in humans across
      Canada. In Quebec, changes of ceftiofur resistance in chicken Salmonella
      Heidelberg and Escherichia coli isolates appear related to changing levels of
      ceftiofur use in hatcheries during the study period, from highest to lowest
      levels before and after a voluntary withdrawal, to increasing levels after
      reintroduction of use (62% to 7% to 20%, and 34% to 6% to 19%, respectively).
      These events provide evidence that ceftiofur use in chickens results in extended
      spectrum cephalosporin resistance in bacteria from chicken and humans. To ensure
      the continued effectiveness of extended-spectrum cephalosporins for treating
      serious infections in humans, multidisciplinary efforts are needed to scrutinize
      and, where appropriate, limit use of ceftiofur in chicken production in Canada.

PMID- 20031043
TI  - Healthcare-associated viral gastroenteritis among children in a large pediatric
      hospital, United Kingdom.
AB  - Viruses are the major pathogens of community-acquired (CA) acute gastroenteritis
      (AGE) in children, but their role in healthcare-associated (HA) AGE is poorly
      understood. Children with AGE hospitalized at Alder Hey Children's Hospital,
      Liverpool, UK, were enrolled over a 2-year period. AGE was classified as HA if
      diarrhea developed > or =48 hours after admission. Rotavirus, norovirus,
      adenovirus 40/41, astrovirus, and sapovirus were detected by PCR. A total of 225
      children with HA-AGE and 351 with CA-AGE were enrolled in the study. HA viral
      gastroenteritis constituted one fifth of the diarrheal diseases among
      hospitalized children and commonly occurred in critical care areas. We detected >
      or =1 virus in 120 (53%) of HA-AGE cases; rotavirus (31%), norovirus (16%), and
      adenovirus 40/41 (15%) were the predominant viruses identified. Molecular
      evidence indicated rotaviruses and noroviruses were frequently introduced into
      the hospital from the community. Rotavirus vaccines could substantially reduce
      the incidence of HA-AGE in children.

PMID- 20031044
TI  - Meningitis and a febrile vomiting illness caused by echovirus type 4, Northern
      Territory, Australia.
AB  - In July 2007, a cluster of meningitis cases caused by an echovirus 4 strain was
      detected in 1 indigenous community in the Top End of the Northern Territory of
      Australia. Illness was characterized by fever, vomiting, and headache. Over the
      next 4 months, additional cases of meningitis and the fever and vomiting syndrome
      emerged in other indigenous communities and subsequently in the major urban
      center of Darwin. We describe the epidemiology of 95 laboratory-confirmed
      meningitis cases and conclude that the epidemic fever and vomiting syndrome was
      caused by the same enterovirus. Nucleotide sequencing of the whole genome
      verified this enterovirus (AUS250G) as a strain of echovirus type 4. Viral
      protein 1 nucleotide sequencing demonstrated 96% homology with an echovirus 4
      strain responsible for a large outbreak of meningitis in the Yanbian Prefecture
      of China in 1996.

PMID- 20031045
TI  - Methicillin-resistant and -susceptible Staphylococcus aureus infections in dogs.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become a pathogen of
      animals. To compare types of infections, clinical outcomes, and risk factors
      associated with MRSA in dogs with those associated with methicillin-susceptible
      Staphylococcus aureus (MSSA) infections, we conducted a case-control study at 3
      veterinary referral hospitals in the United States and Canada during 2001-2007.
      Risk factors analyzed were signalment, medical and surgical history, and
      infection site. Among 40 dogs with MRSA and 80 with MSSA infections, highest
      prevalence of both infections was found in skin and ears. Although most (92.3%)
      dogs with MRSA infections were discharged from the hospital, we found that
      significant risk factors for MRSA infection were receipt of antimicrobial drugs
      (odds ratio [OR] 3.84, p = 0.02), Beta-lactams (OR 3.58, p = 0.04), or
      fluoroquinolones (OR 5.34, p = 0.01), and intravenous catheterization (OR 3.72, p
      = 0.02). Prudent use of antimicrobial drugs in veterinary hospitals is advised.

PMID- 20031046
TI  - Actinobaculum schaalii, a common uropathogen in elderly patients, Denmark.
AB  - Actinobaculum schaalii can cause urinary tract infections and septicemia but is
      difficult to identify by cultivation. To obtain a fast diagnosis and identify A.
      schaalii, we developed a TaqMan real-time quantitative PCR. Routine urine samples
      were obtained from 177 hospitalized patients and 75 outpatients in Viborg County,
      Denmark, in 2008-2009. The PCR detected A. schaalii in 22% of samples from
      patients >60 years of age. This assay showed that A. schaalii is more common than
      implied by routine cultivation. In 90% of PCR-positive urine samples, other
      common uropathogens were identified. This finding suggests that A. schaalii is a
      common, undetected, bacterial pathogen. Our results suggest that A. schaalii may
      be a more common pathogen than previously thought, especially in patients with
      unexplained chronic urinary tract infections, who are often treated with
      trimethoprim or ciprofloxacin, to which A. schaalii is resistant.

PMID- 20031047
TI  - Norovirus gastroenteritis outbreak with a secretor-independent susceptibility
      pattern, Sweden.
AB  - Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis
      among adults. Susceptibility to disease has been associated with histo-blood
      group antigens and secretor status; nonsecretors are almost completely resistant
      to disease. We report a foodborne outbreak of GI.3 NoV gastroenteritis that
      affected 33/83 (40%) persons. Symptomatic disease was as likely to develop in
      nonsecretors as in secretors (odds ratio [OR] 1.41, 95% confidence interval [CI]
      0.46-4.36 vs. OR 0.71, 95% CI 0.23-2.18, p = 0.57). Moreover, no statistical
      difference in susceptibility was found between persons of different Lewis or ABO
      phenotypes. The capsid gene of the outbreak strain shares high amino acid
      homology with the Kashiwa645 GI.3 strain, previously shown to recognize
      nonsecretor saliva, as well as synthetic Lewis a. This norovirus outbreak
      affected persons regardless of secretor status or Lewis or ABO phenotypes.

PMID- 20031048
TI  - Food reservoir for Escherichia coli causing urinary tract infections.
AB  - Closely related strains of Escherichia coli have been shown to cause
      extraintestinal infections in unrelated persons. This study tests whether a food
      reservoir may exist for these E. coli. Isolates from 3 sources over the same time
      period (2005-2007) and geographic area were compared. The sources comprised
      prospectively collected E. coli isolates from women with urinary tract infection
      (UTI) (n = 353); retail meat (n = 417); and restaurant/ready-to-eat foods (n =
      74). E. coli were evaluated for antimicrobial drug susceptibility and O:H
      serotype and compared by using 4 different genotyping methods. We identified 17
      clonal groups that contained E. coli isolates (n = 72) from >1 source. E. coli
      from retail chicken (O25:H4-ST131 and O114:H4-ST117) and honeydew melon (O2:H7
      ST95) were indistinguishable from or closely related to E. coli from human UTIs.
      This study provides strong support for the role of food reservoirs or foodborne
      transmission in the dissemination of E. coli causing common community-acquired
      UTIs.

PMID- 20031049
TI  - Serologic cross-reactivity with pandemic (H1N1) 2009 virus in pigs, Europe.
AB  - We tested serum samples from pigs infected or vaccinated with European swine
      influenza viruses (SIVs) in hemagglutination-inhibition assays against pandemic
      (H1N1) 2009 virus and related North American SIVs. We found more serologic cross
      reaction than expected. Data suggest pigs in Europe may have partial immunity to
      pandemic (H1N1) 2009 virus.

PMID- 20031050
TI  - Hospitalizations for pandemic (H1N1) 2009 among Maori and Pacific Islanders, New
      Zealand.
AB  - Community transmission of influenza A pandemic (H1N1) 2009 was followed by high
      rates of hospital admissions in the Wellington region of New Zealand,
      particularly among Maori and Pacific Islanders. These findings may help health
      authorities anticipate the effects of pandemic (H1N1) 2009 in other communities.

PMID- 20031051
TI  - Pandemic (H1N1) 2009 surveillance and prevalence of seasonal influenza,
      Singapore.
AB  - On April 25, 2009, Singapore implemented strict containment measures for pandemic
      (H1N1) 2009 with enhanced surveillance and hospital isolation. In the first
      month, seasonal influenza, predominantly virus subtype H3N2, was diagnosed for
      32% of patients with acute febrile respiratory illness. Our findings underscore
      the high prevalence of seasonal influenza in Singapore.

PMID- 20031052
TI  - Reemergence of syphilis in Martinique, 2001-2008.
AB  - Syphilis reemerged in Martinique in 2004 and initially affected 3 HIV-infected
      patients. By March 2008, syphilis was diagnosed for 37 men and 18 women. As of
      October 31, 2009, this outbreak had not yet been brought under control. It
      initially affected mainly men who had sex with men before it spread to
      heterosexual persons, minority group members, and crack cocaine users.

PMID- 20031053
TI  - Seagulls and beaches as reservoirs for multidrug-resistant Escherichia coli.
AB  - A variety of extended-spectrum Beta-lactamase-producing Escherichia coli
      isolates, with a high rate of cefotaximase-15 resistance, were identified in
      seagull feces from Porto, Portugal, beaches. Beaches may therefore present a risk
      to public health because of the potential pathogen-spreading capacity of
      migratory birds.

PMID- 20031054
TI  - Cluster of serogroup W135 meningococci, southeastern Florida, 2008-2009.
AB  - Recently, 14 persons in southeastern Florida were identified with Neisseria
      meningitidis serogroup W135 invasive infections. All isolates tested had matching
      or near-matching pulsed-field gel electrophoresis patterns and belonged to the
      multilocus sequence type 11 clonal complex. The epidemiologic investigation
      suggested recent endemic transmission of this clonal complex in southeastern
      Florida.

PMID- 20031055
TI  - Human group A streptococci virulence genes in bovine group C streptococci.
AB  - Phage-encoded virulence genes of group A streptococci were detected in 10 (55.6%)
      of 18 isolates of group C streptococci that had caused bovine mastitis. Bovine
      isolates carried other genetic determinants, such as composite transposon
      Tn1207.3/F10394.4 (100%) and antimicrobial drug resistance genes erm(B)/erm(A)
      (22.2%), linB (16.6%), and tet(M)/tet(O) (66.7%), located on mobile elements.

PMID- 20031056
TI  - Perceptions and reactions with regard to pneumonic plague.
AB  - We assessed perceptions and likely reactions of 1,005 UK adults to a hypothetical
      terrorist attack involving pneumonic plague. Likely compliance with official
      recommendations ranged from good (98% would take antimicrobial drugs) to poor
      (76% would visit a treatment center). Perceptions about plague were associated
      with these intentions.

PMID- 20031057
TI  - Rapid displacement of dengue virus type 1 by type 4, Pacific region, 2007-2009.
AB  - Since 2000-2001, dengue virus type 1 has circulated in the Pacific region.
      However, in 2007, type 4 reemerged and has almost completely displaced the
      strains of type 1. If only 1 serotype circulates at any time and is replaced
      approximately every 5 years, DENV-3 may reappear in 2012.

PMID- 20031058
TI  - Hepatitis E epidemic, Uganda.
AB  - In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of
      northern Uganda where no previous epidemics had been documented. This outbreak
      has progressed to become one of the largest hepatitis E outbreaks in the world.
      By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths.

PMID- 20031059
TI  - Novel human parechovirus, Sri Lanka.
AB  - Of 362 fecal samples collected from children with acute gastroenteritis in Sri
      Lanka during 2005-2006, 30 (8.3%) were positive for human parechovirus (HPeV) by
      reverse transcription-PCR. A novel HPeV, designated as HPeV10, was identified in
      2 samples by sequence analysis of the viral protein 1 gene of the detected HPeVs.

PMID- 20031060
TI  - Broiler chickens as source of human fluoroquinolone-resistant Escherichia coli,
      Iceland.
AB  - To investigate feed as a source for fluoroquinolone-resistant Escherichia coli in
      broiler chickens, we compared antimicrobial drug-resistant E. coli from broiler
      feed and broilers with ciprofloxacin-resistant human clinical isolates by using
      pulsed-field gel electrophoresis. Feed was implicated as a source for
      ciprofloxacin-resistant broiler-derived E. coli and broilers as a source for
      ciprofloxacin-resistant human-derived E. coli.

PMID- 20031061
TI  - Human listeriosis caused by Listeria ivanovii.
AB  - Two species of Listeria are pathogenic; L. monocytogenes infects humans and
      animals, and L. ivanovii has been considered to infect ruminants only. We report
      L. ivanovii-associated gastroenteritis and bacteremia in a man. This isolate was
      indistinguishable from prototypic ruminant strains. L. ivanovii is thus an
      enteric opportunistic human pathogen.

PMID- 20031062
TI  - Acute encephalopathy associated with influenza A infection in adults.
AB  - We report acute encephalopathy associated with influenza A infection in 3 adults.
      We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL
      8 and CCL2/MCP-1 (CSF/plasma ratios > or =3), and interleukin-6, CXCL10/IP-10,
      but no evidence of viral neuroinvasion. Patients recovered without sequelae.
      Hyperactivated cytokine response may play a role in pathogenesis.

PMID- 20031063
TI  - Enterotoxigenic Escherichia coli multilocus sequence types in Guatemala and
      Mexico.
AB  - The genetic backgrounds of 24 enterotoxigenic Escherichia coli (ETEC) strains
      from Mexico and Guatemala expressing heat-stable toxin (ST) and coli surface
      antigen 6 (CS6) were analyzed. US travelers to these countries and resident
      children in Guatemala were infected by ETEC strains of sequence type 398,
      expressing STp and carrying genetically identical CS6 sequences.

PMID- 20031064
TI  - Laboratory surge capacity and pandemic influenza.
AB  - In this issue, Crawford et al. describe their experiences running a clinical
      diagnostic laboratory during the first 3 weeks of the influenza A pandemic (H1N1)
      2009 outbreak (1). During the early weeks of the outbreak, their laboratory,
      which serves 15 hospitals and affiliated physician practices in the greater New
      York City metropolitan area, experienced an approximately 8x increase in
      respiratory virus testing, reaching a maximum of about 900 samples processed in 1
      day.

PMID- 20031065
TI  - Fatal case of pneumonia associated with pandemic (H1N1) 2009 in HIV-positive
      patient.

PMID- 20031066
TI  - Human herpesvirus 8 in healthy blood donors, Argentina.

PMID- 20031067
TI  - Real-time PCR for diagnosis of oculoglandular tularemia.

PMID- 20031068
TI  - Increase in serotype 6C pneumococcal carriage, United Kingdom.

PMID- 20031069
TI  - Oseltamivir- and amantadine-resistant influenza virus A (H1N1).

PMID- 20031070
TI  - Pandemic (H1N1) 2009 reinfection, Chile.

PMID- 20031071
TI  - Skin lesion caused by ST398 and ST1 MRSA, Spain.

PMID- 20031072
TI  - Identification of a rotavirus G12 strain, Indonesia.

PMID- 20031073
TI  - Age-based human influenza A virus (H5N1) infection patterns, Egypt.

PMID- 20031074
TI  - Imported chikungunya virus infection.

PMID- 20031075
TI  - Distinct molecular signature of bovine spongiform encephalopathy prion in pigs.

PMID- 20031076
TI  - Parvovirus 4 in blood donors, France.

PMID- 20031077
TI  - Otomastoiditis caused by Mycobacterium abscessus, The Netherlands.

PMID- 20031078
TI  - Diseases tracked by using Google trends, Spain.

PMID- 20031079
TI  - Detection of newly described astrovirus MLB1 in stool samples from children.

PMID- 20031080
TI  - Optimal therapy for multidrug-resistant Acinetobacter baumannii.

PMID- 20031082
TI  - Tasty bits a Dutch treat.

PMID- 20031083
TI  - Socio-demographic and geographic analysis of overweight and obesity in Canadian
      adults using the Canadian Community Health Survey (2005).
AB  - Using the 2005 Canadian Community Health Survey, this study examined how
      overweight and obesity in Canadian adults are distributed across socio
      demographic and geographic groupings. Overweight and obesity prevalence were
      modeled against socio-demographic indicators using Poisson regression and were
      assessed geographically using choropleth maps. The Gini coefficient was used to
      assess the distribution of prevalence across risk groups. The potential impacts
      of high risk versus population-based prevention approaches on the population
      prevalence of obesity were also examined. Of adults aged 25 to 64 years, 17% were
      obese and 53% were overweight or obese, with the highest proportions observed in
      older age groups, among those who were physically inactive, white or non
      immigrant, with low educational levels, and living in the prairie and east coast
      regions. Recalculation of obesity rates under the different prevention scenarios
      demonstrated that population-based approaches could achieve a four-fold greater
      decrease in obesity cases than high risk approaches, highlighting the need for
      broader population strategies for obesity prevention in Canada.

PMID- 20031084
TI  - Using cancer registry data: agreement in cause-of-death data between the Ontario
      Cancer Registry and a longitudinal study of breast cancer patients.
AB  - Data from the Ontario Cancer Registry (OCR) were compared with data from a multi
      centred prospective cohort of 1655 node-negative breast cancer patients with
      intensive clinical follow-up. Agreement in cause of death was evaluated using
      kappa statistics. The accuracy of OCR classification was evaluated against the
      Mount Sinai Hospital (MSH) study oncologist's interpretation of intensely
      followed, cohort-collected data as the reference standard. The two sources showed
      a high level of agreement (kappa statistic [kappa] = 0.88; 95% confidence
      interval [CI]: 0.86, 0.90) in vital status and cause of death. Among those cases
      where both sources reported a death, the OCR had a sensitivity of 95% (95% CI:
      90.5, 98.8) and a specificity of 88% (95% CI: 79.6, 92.4). The OCR is a valuable
      tool for epidemiologic studies of breast cancer to acquire adequate and easily
      attainable cause-of-death information.

PMID- 20031085
TI  - Using administrative data to understand the geography of case ascertainment.
AB  - We examined the geographic variability of information generated from different
      case definitions of childhood asthma derived from administrative health data used
      in Alberta, Canada. Our objective was to determine if analyses based on different
      case ascertainment algorithms identify geographic clusters in the same region of
      the study area. Our study group was based on a closed cohort of asthmatic
      children born in 1988. We used a spatial scan statistic to identify variations in
      the approximate location of geographic clusters of asthma based on different case
      definitions. Our results indicate that the geographic patterns are not greatly
      affected by the case ascertainment algorithm or the source of data. For example,
      asthmatics identified from medical claims data showed similar clustering to
      asthmatics defined through hospitalization and emergency department data.
      However, estimates of prevalence and incidence require careful consideration and
      validation against other data sources.

PMID- 20031086
TI  - Association of obesity with mood and anxiety disorders in the adult general
      population.
AB  - Obesity is a major health concern. It has been implicated as a risk factor for
      several physical illnesses, functional limitations and poor quality of life.
      However, while the physical consequences of obesity are well established, the
      relationship between obesity and mental health is still unclear. This study used
      data collected in the Canadian Community Health Survey, cycle 3.1 (2005) to
      examine this relationship in adults 20 to 64 years old. Obesity was significantly
      associated with mood disorders, but not with anxiety disorders. When adjusting
      for sex, place of birth, smoking, and functional limitations, all of which were
      significantly associated with obesity, the odds of obesity remained significantly
      higher in persons with mood disorders (with or without anxiety disorders). It is
      still unclear whether the relationship between obesity and depression is causal,
      and if so, whether obesity causes depression or depression causes obesity.
      Implications for health care providers and suggestions for future research are
      discussed.

PMID- 20031087
TI  - The clinical effectiveness and cost-effectiveness of testing for cytochrome P450
      polymorphisms in patients with schizophrenia treated with antipsychotics: a
      systematic review and economic evaluation.
AB  - OBJECTIVE: To determine whether testing for cytochrome P450 (CYP) polymorphisms
      in adults entering antipsychotic treatment for schizophrenia leads to improvement
      in outcomes, is useful in medical, personal or public health decision-making, and
      is a cost-effective use of health-care resources. DATA SOURCES: The following
      electronic databases were searched for relevant published literature: Cochrane
      Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of
      Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment
      database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation
      Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA)
      Registry and the Centre for Health Economics website. In addition, publicly
      available information on various genotyping tests was sought from the internet
      and advisory panel members. REVIEW METHODS: A systematic review of analytical
      validity, clinical validity and clinical utility of CYP testing was undertaken.
      Data were extracted into structured tables and narratively discussed, and meta
      analysis was undertaken when possible. A review of economic evaluations of CYP
      testing in psychiatry and a review of economic models related to schizophrenia
      were also carried out. RESULTS: For analytical validity, 46 studies of a range of
      different genotyping tests for 11 different CYP polymorphisms (most commonly
      CYP2D6) were included. Sensitivity and specificity were high (99-100%). For
      clinical validity, 51 studies were found. In patients tested for CYP2D6, an
      association between genotype and tardive dyskinesia (including Abnormal
      Involuntary Movement Scale scores) was found. The only other significant finding
      linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the
      inclusion criteria for clinical utility. One economic evaluation assessing the
      costs and benefits of CYP testing for prescribing antidepressants and 28 economic
      models of schizophrenia were identified; none was suitable for developing a model
      to examine the cost-effectiveness of CYP testing. CONCLUSIONS: Tests for
      determining genotypes appear to be accurate although not all aspects of
      analytical validity were reported. Given the absence of convincing evidence from
      clinical validity studies, the lack of clinical utility and economic studies, and
      the unsuitability of published schizophrenia models, no model was developed;
      instead key features and data requirements for economic modelling are presented.
      Recommendations for future research cover both aspects of research quality and
      data that will be required to inform the development of future economic models.

PMID- 20031088
TI  - Augmentation and combination strategies for complicated depression.
AB  - Approximately half of patients with depression do not respond or only partially
      respond to first-line antidepressant monotherapy. To enhance treatment response,
      the treating clinician may choose to augment the antidepressant with a
      nonantidepressant agent or combine the initial antidepressant with another
      antidepressant, typically of another class. Although the augmentation and
      combination strategies reviewed here appear relatively safe and effective,
      additional controlled studies are needed to compare these treatment options,
      guide treatment selection for individual patients, and answer questions regarding
      the duration of combination or augmentation strategies for patients with
      treatment-resistant depression.

PMID- 20031089
TI  - Diagnosing bipolar disorder in children and adolescents.
AB  - Pediatric-onset bipolar disorder is common but often difficult to diagnose in
      younger patients. Clinicians should be sure to establish the presence of a full
      manic episode to make the diagnosis of bipolar I disorder. Because adult criteria
      are used for children and adolescents, clinicians also should be aware of
      developmental norms that can help to make an accurate diagnosis. Bipolar disorder
      NOS and other disorders in children and adolescents may be prodromal states for
      bipolar disorder, especially in the presence of a positive family history.

PMID- 20031090
TI  - Pharmacotherapeutic treatment strategies for antidepressant nonresponse.
AB  - Patients who do not respond to initial antidepressant treatment are more
      difficult to treat and have lower odds of remission than those who fully or
      partially respond to initial pharmacotherapy. Potential treatment options for
      nonresponders include combination and switching strategies, both of which can be
      done within a single class of medications or across medication classes. Choosing
      the correct strategy and appropriate pharmaceutical option or options requires
      consideration of not only algorithm recommendations, but also a variety of
      variables including, but not limited to, the patient's symptom and side effect
      profiles.

PMID- 20031091
TI  - Pain and the brain 2: the recognition and management of chronic pain in primary
      care.
AB  - Somatic symptoms are the foremost reason that individuals seek medical care, and
      most patients present with these symptoms in the primary care setting. Thus,
      clinicians must be able to recognize the manifestations of chronic pain as well
      as devise and implement an individualized treatment strategy that will relieve
      pain, manage any psychiatric comorbidities, and improve functioning and quality
      of life. This video includes 3 example patient cases and expert recommendations
      on accurately identifying, diagnosing, and treating the illnesses related to
      chronic pain, including comorbid depression and anxiety.

PMID- 20031092
TI  - Safety and tolerability of bipolar disorder treatment in youth.
AB  - Bipolar disorder is an increasingly common diagnosis given to children and
      adolescents. Most studies of lithium, anticonvulsants, and atypical
      antipsychotics have been conducted in adult populations, but new data are
      providing information on the safety and tolerability of these medications for
      treating children and adolescents. Although generally well tolerated,
      psychotropic agents have different side effect profiles that should be considered
      when planning treatment regimens for pediatric patients. Additional controlled
      and comparative trials are needed on the safety and tolerability of these
      medications in young patients, especially for long-term maintenance treatment.

PMID- 20031093
TI  - Combining antidepressant therapies from the initiation of treatment: a paradigm
      shift for major depression.

PMID- 20031096
TI  - The role of divalproex plus olanzapine in outpatient mixed-episode bipolar I
      disorder.

PMID- 20031094
TI  - Exploratory data mining analysis identifying subgroups of patients with
      depression who are at high risk for suicide.
AB  - OBJECTIVE: Although prior research has identified a number of separate risk
      factors for suicide among patients with depression, little is known about how
      these factors may interact to modify suicide risk. Using an empirically based
      decision tree analysis for a large national sample of Veterans Affairs (VA)
      health system patients treated for depression, we identified subgroups with
      particularly high or low rates of suicide. METHOD: We identified 887,859 VA
      patients treated for depression between April 1, 1999, and September 30, 2004.
      Randomly splitting the data into 2 samples (primary and replication samples), we
      developed a decision tree for the primary sample using recursive partitioning. We
      then tested whether the groups developed within the primary sample were
      associated with increased suicide risk in the replication sample. RESULTS: The
      exploratory data analysis produced a decision tree with subgroups of patients at
      differing levels of risk for suicide. These were identified by a combination of
      factors including a co-occurring substance use disorder diagnosis, male sex,
      African American race, and psychiatric hospitalization in the past year. The
      groups developed as part of the decision tree accurately discriminated between
      those with and without suicide in the replication sample. The patients at highest
      risk for suicide were those with a substance use disorder who were non-African
      American and had an inpatient psychiatric stay within the past 12 months.
      CONCLUSIONS: Study findings suggest that the identification of depressed patients
      at increased risk for suicide is improved through the examination of higher order
      interactions between potential risk factors.

PMID- 20031098
TI  - Early career psychiatry.

PMID- 20031099
TI  - Commentaries on peer review and the evolving journal.

PMID- 20031097
TI  - Presenting ADHD symptoms, subtypes, and comorbid disorders in clinically referred
      adults with ADHD.
AB  - OBJECTIVE: Despite the increasing presentation of attention-deficit/hyperactivity
      disorder (ADHD) in adults, many practitioners remain reluctant to assess
      individuals for ADHD, in part related to the relative lack of data on the
      presenting symptoms of ADHD in adulthood. Comorbidity among adults with ADHD is
      also of great interest due to the high rates of psychiatric comorbidity, which
      can lead to a more persistent ADHD among adults. METHOD: We assessed 107 adults
      with ADHD of both sexes (51% female; mean +/- SD of 37 +/- 10.4 years) using
      structured diagnostic interviews. Using DSM-IV symptoms, we determined DSM-IV
      subtypes. The study was conducted from 1998 to 2003. RESULTS: Inattentive
      symptoms were most frequently endorsed (> 90%) in adults with ADHD. Using current
      symptoms, 62% of adults had the combined subtype, 31% the inattentive only
      subtype, and 7% the hyperactive/impulsive only subtype. Adults with the combined
      subtype had relatively more psychiatric comorbidity compared to those with the
      predominately inattentive subtype. Women were similar to men in the presentation
      of ADHD. CONCLUSION: Adults with ADHD have prominent inattentive symptoms of
      ADHD, necessitating careful questioning of these symptoms when evaluating these
      individuals.

PMID- 20031100
TI  - Learning to review.

PMID- 20031101
TI  - Peer review perspective for early career psychiatrists.

PMID- 20031102
TI  - Peer review by early career psychiatrists: an opportunity for development.

PMID- 20031103
TI  - The evolution of the psychiatry research journal.

PMID- 20031104
TI  - Peer review in early career: just say yes!

PMID- 20031105
TI  - Do glutamatergic agents represent a new class of antidepressant drugs? Part 2.

PMID- 20031106
TI  - Treatment of morbidly obese psychotic patients with molindone: three case
      reports.

PMID- 20031107
TI  - Symptom exacerbation in tourette syndrome due to bacterial reinfection.

PMID- 20031108
TI  - Myxedema madness rapidly reversed with levothyroxine.

PMID- 20031109
TI  - The impact of ethnicity on metabolic outcomes during treatment with
      antipsychotics: complexities abound.

PMID- 20031110
TI  - Body mass index and response to antidepressants in depressed research subjects.

PMID- 20031111
TI  - Glyburide: caution for efficacy and fetal programming effects.

PMID- 20031112
TI  - Intrauterine progestins, progesterone antagonists, and receptor modulators: a
      review of gynecologic applications.
AB  - Intrauterine progestins, progesterone receptor modulators, and antagonists have
      many important current and potential gynecologic applications. This article will
      describe the evidence for use of intrauterine progestin for common gynecologic
      conditions beyond its important role in contraception. We will review the
      evidence for use of intrauterine progestin delivery for menorrhagia,
      endometriosis management, adenomyosis treatment, uterine fibroids, endometrial
      hyperplasia, and its concurrent use in women on hormone replacement therapy or
      tamoxifen.

PMID- 20031113
TI  - Hypochloremia and hyponatremia as the initial presentation of cystic fibrosis in
      three adults.
AB  - Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene. Most diagnoses of CF are made during infancy
      or childhood, and are based on respiratory or digestive involvement. Initial
      extracellular dehydration leading to the diagnosis of CF is usual in infants but
      has only exceptionally been reported in adults. We describe three new adult cases
      of CF initially presenting with depletive hyponatremia and hypochloremia
      following exposure to heat. At first consultation, these patients had no symptoms
      suggestive of CF. One patient presented with a seizure induced by hyponatremia.
      The two other patients were siblings carrying a novel c.4434insA mutation in exon
      24 of CFTR. Acute dehydration is a very rare initial manifestation of CF but may
      be life-threatening. The possibility of CF should not be ignored in cases of
      depletive hyponatremia, hypochloremia or hypokalemic metabolic alkalosis, even in
      otherwise healthy patients.

PMID- 20031114
TI  - Genetics of pheochromocytoma and paraganglioma: new developments.
AB  - Since 2000, several new susceptibility genes for hereditary pheochromocytoma or
      paraganglioma have been discovered. The aim of this review is to highlight how
      these discoveries have improved our knowledge on the mode of inheritance of these
      tumors and also on their molecular pathogenesis. Concerning this specific point,
      we will show that the different key players of tumorigenesis can converge on two
      pathways, the first being the hypoxia/angiogenesis pathway and the second being
      the control of neural crest cell development pathway. Finally, practical issues
      are considered; for us, it would be preferable to apply easy-to-identify clinical
      predictors to preselect patients eligible for molecular testing in order to
      improve the efficiency of these high-cost tests.

PMID- 20031115
TI  - Mismatch between classroom furniture and anthropometric measures in Chilean
      schools.
AB  - Children spend about five hours per day sitting down while doing their school
      work. Considering this as well as the potential inadequate use of school
      furniture, it is likely that some anatomical-functional changes and problems in
      the learning process may occur. The aim of this study was to compare furniture
      sizes within three different schools with the anthropometric characteristics of
      Chilean students in the Valparaiso region, in order to evaluate the potential
      mismatch between them. The sample consisted of 195 volunteer students (94 male,
      101 female) of the 8th grade, ranging from 12.5 to 14.5 years of age from 3
      different schools. Regarding the methodology, 6 anthropometric measures (Stature,
      Popliteal height, Buttock-popliteal length, Elbow height while sitting, Hip
      width, Thigh thickness and Subscapular height) were gathered, as well as 8
      dimensions from the school furniture. For the evaluation of classroom furniture a
      match criterion equation was defined. After considering the existing classroom
      furniture dimensions in each match criterion equation, the anthropometric
      characteristics of the considered population were compared in order to determine
      the mismatch between them. Results indicated that seat height, which should be
      considered as the starting point for the design of classroom furniture, was
      appropriate for students' popliteal height in only 14% of the 2 out of the 3
      schools, and 28% in the third. Seat to desk height was too high and mismatched
      99% of the students in one school and 100% in the others. Therefore, it was
      possible to conclude that the classroom's furniture was inadequate in almost all
      the analyzed cases and subjects. It is possible that the high mismatch percentage
      found between furniture and students' anthropometry can be associated to the fact
      that the acquisition and selection of the furniture was made without any
      ergonomic concern or criteria.

PMID- 20031116
TI  - A standardized method for measuring the force required to join wire harnesses and
      sparkplugs.
AB  - Understanding the forces required to insert a sparkplug wire (wire) onto a
      sparkplug (plug), independent of worker variation, is important for ergonomists,
      engineers, and designers. This paper describes a methodology for measuring the
      forces required to seat a wire onto a plug. A three-axis programmable mill was
      used to insert wires onto plugs mounted on a force transducer. Inflection points
      and slopes of the force-displacement curves were found to correspond to
      mechanical events as the plug and wire were joined. These events were further
      isolated by dissecting the wires to better understand the force contribution of
      each wire component. Liner superposition was then used to show that each of these
      force elements may be added to estimate the total force required to seat a wire
      onto a plug. This methodology may be used to quantify the effects of design
      choices, lubricants (wet and dry), and pre-working on axial insertion forces
      associated with sparkplugs and other insertions. This paper does not address
      worker abilities or variation, however, the methodology and equipment described
      may provide a foundation for the exploration of worker ability, variation and
      work techniques.

PMID- 20031118
TI  - Psychopathy and fearlessness: an interhemispheric imbalance perspective.

PMID- 20031117
TI  - Effect of a pulsed CO2 laser and fluoride on the prevention of enamel and dentine
      erosion.
AB  - OBJECTIVE: The hypotheses of this study was that pulsed CO(2) laser (lambda=10.6
      microm) treatment in combination (or not) with previous fluoride gel application
      could increase the resistance of enamel and dentine to erosion, throughout
      successive erosive challenges. DESIGN: Thirty-two bovine specimens of enamel and
      of root dentine were flattened, polished and randomly assigned to the following
      treatments (n=8): fluoride (F), laser (L), fluoride+laser (FL) or no treatment as
      negative control (C). The treated specimens were submitted to demineralization
      (0.3% citric acid, pH 2.45, for 5 min) and remineralization (artificial saliva,
      for 60 min) cycles, three times a day, for 3 days. Dental surface loss as well as
      the concentration of calcium, phosphorus and fluoride in the demineralizing
      solutions were determined after each cycling day. Enamel and dentine were
      analysed separately using repeated measures ANOVA for ranks (alpha=0.05).
      RESULTS: The association between fluoride and laser (FL) resulted in the lowest
      enamel and dentine surface loss values throughout the cycles, differing
      significantly from the control group. No clear benefit of FL over the F or L
      treatments was observed. There was a non-significant trend (p>0.05) for FL to
      release less calcium, phosphorus and fluoride into the demineralizing solutions
      when compared to the other groups. CONCLUSIONS: Pulsed CO(2) laser (lambda=10.6
      microm) alone was not able to prevent enamel or dentine surface losses due to
      erosion. Laser treatment in combination with fluoride showed some protection, but
      the effect does not appear to be synergistic.

PMID- 20031119
TI  - Lactose as an inexpensive starting material for the preparation of aldohexos-5
      uloses: synthesis of L-ribo and D-lyxo derivatives.
AB  - Partially protected derivatives of L-ribo- and D-lyxo-aldohexos-5-ulose have been
      prepared starting from triacetonlactose dimethyl acetal derivatives. Key steps of
      the synthetic sequences are (a) the synthesis of 4'-deoxy-4'-eno- and 6'-deoxy-5'
      eno lactose derivatives, and (b) the epoxidation-methanolysis of the above
      mentioned enol ethers to give 1,5-bis-glycopyranosides, masked form of the target
      1,5-dicarbonyl hexoses.

PMID- 20031120
TI  - Synthesis and characterization of thermo-sensitive semi-IPN hydrogels based on
      poly(ethylene glycol)-co-poly(epsilon-caprolactone) macromer, N
      isopropylacrylamide, and sodium alginate.
AB  - Thermo-sensitive semi-IPN hydrogels were prepared via in situ copolymerization of
      N-isopropylacrylamide (NIPAAm) with poly(ethylene glycol)-co-poly(epsilon
      caprolactone) (PEG-co-PCL) macromer in the presence of sodium alginate by UV
      irradiation technology. The effects of the sodium alginate content, temperature,
      and salt on the swelling behavior of the as-obtained hydrogels were studied. The
      results showed that the swelling ratio of the hydrogels increased with the
      increasing sodium alginate content at the same temperature, and decreased with
      the increase in temperature. The salt sensitivity of the semi-IPN hydrogels was
      dependent on the content of sodium alginate introduced in the hydrogels. The
      mechanical rheology of the hydrogels and in vitro release behavior of bovine
      serum albumin (BSA) in situ encapsulated within the hydrogels were also
      investigated. It was found that the introduction of sodium alginate with semi-IPN
      structure improved mechanical strength of the hydrogels and the cumulative
      release percentage of BSA from the hydrogels. Such double-sensitive semi-IPN
      hydrogel materials could be exploited as potential candidates for drug delivery
      carriers.

PMID- 20031122
TI  - [Giant pancreatic abscess].

PMID- 20031121
TI  - A unique unresponsive CD4+ T cell phenotype post TCR antagonism.
AB  - The functional outcomes of the T cell's interaction with the peptide:MHC complex
      can be dramatically altered by the introduction of a single amino acid
      substitution. Previous studies have described the varied effects of these altered
      peptide ligands (APL) on T cell responses. These outcomes of T cell interaction
      with an APL include the induction of clonal unresponsiveness (anergy) and
      inhibition of T cell responses (antagonism). The phenotype of peptide-induced
      anergy, i.e. low proliferation and low IL-2 production, has been extensively
      described, and a number of groups have demonstrated antagonism. However, the
      response of T cells to an agonist ligand after encountering an antagonistic
      stimulus has not been previously characterized. Here, we show that T cells post
      antagonism fail to proliferate but produce large quantities of IL-2 upon
      stimulation with their wild type ligand. This unique phenotype is not due to
      differences in IL-2 receptor expression or rates of apoptosis, and cannot be
      overcome by the addition of recombinant IL-2. The response of CD4 T cells to
      agonist stimulation after encountering an antagonist is a novel phenotype, and is
      distinct from previously described forms of anergy.

PMID- 20031123
TI  - Removal of ring artifacts in computed tomographic imaging using iterative center
      weighted median filter.
AB  - A new iterative center weighted median filter (ICWMF) for ring artifact reduction
      from the micro-computed tomographic (micro-CT) image is proposed in this paper.
      The center weight of the median filter is computed based on the characteristic of
      the ring artifact in the mean curve of the projection data. The filter operates
      on the deviation of the mean curve to smooth the ring generating peaks and
      troughs iteratively while preserving the details due to image. A convergence
      criterion for the iterative algorithm is determined from the distribution of the
      local deviation computed from the mean curve deviation. The estimate of the mean
      curve obtained using the ICWMF is used to correct the ring corrupted projection
      data from which reconstruction gives the ring artifact suppressed micro-CT image.
      Test results on both the synthetic and real images demonstrate that the ring
      artifacts can be more effectively suppressed using our method as compared to
      other ring removal techniques reported in the literature.

PMID- 20031124
TI  - Burn mortality in Bangladesh: findings of national health and injury survey.
AB  - OBJECTIVE: The study was designed to explore the epidemiology of burn mortality
      in Bangladesh. METHODS: A population-based cross-sectional survey was conducted
      between January and December 2003. Nationally representative data was collected
      from 171,366 rural and urban households, comprising of a total population of
      819,429. RESULTS: Overall mortality burn rate was 2.2 per 100,000 populations per
      year. The rate was higher amongst females. Most of the deaths were accidental in
      nature, only 5% of deaths were from self-inflected burn. The rate was higher
      amongst the rural population compared to the urban population. About 90% of the
      burn incidences were at home with the kitchen the most frequent place at home for
      burn incidence to occur. A majority, 89%, of the deaths were caused by flame
      burn. Cooking fire, heating fire and fire from kerosene lamps were the major
      sources of flames. The majority of burn deaths occurred during winter season.
      CONCLUSION: Burn is a considerable cause of death in Bangladesh. Females, rural
      dwellers and populations of low socioeconomic condition are more vulnerable to
      burn injury. With simple intervention many of the deaths due to burn can be
      prevented. Considering the magnitude of the problem it is very important to
      address it as a public health problem and develop a national burn prevention
      program.

PMID- 20031126
TI  - Promoting healthy behaviors: how do we get the message across?
AB  - The world is experiencing a rapid rise in chronic health problems, which places
      an enormous burden on health care services. Modifiable health behaviors are
      largely responsible for this high prevalence and incidence of chronic diseases.
      This realization has made initiatives that promote healthy behaviors an
      international and interdisciplinary priority. How can nurses and other health
      care providers get the message across to their patients in order to maximize
      likelihood of leading to desired outcomes? Message tailoring is a well
      established health communication approach shown to increase the persuasiveness of
      message effects in the promotion of healthy behaviors. Message framing is an
      effective message tailoring strategy that has been well-studied in the psychology
      literature over the past 20-plus years across a breadth of health behaviors while
      being severely understudied in the nursing literature. Numerous variables,
      especially those related to individual differences, have been shown to moderate
      message framing effects, a finding of great utility for nursing. This article
      presents a detailed review of the current state of the message framing
      literature, offers specific suggestions for advancing this literature, and
      highlights implications for research, education, and practice, with particular
      attention to nurses.

PMID- 20031127
TI  - Changes in cytokine levels during acute hyperinsulinemia in offspring of type 2
      diabetic subjects.
AB  - OBJECTIVE: To investigate the changes in the levels of cytokines and adhesion
      molecules in response to acute hyperinsulinemia in the offspring of type 2
      diabetic subjects. METHODS: Forty healthy offspring of type 2 diabetic subjects
      and 19 control offspring of healthy parents were included in the study. Twenty
      offspring had normal glucose tolerance (NGT) and twenty offspring impaired
      glucose tolerance (IGT). Insulin sensitivity was determined by the
      hyperinsulinemic euglycemic clamp and insulin secretion with the intravenous
      glucose tolerance test. The levels of cytokines and adhesion molecules were
      measured before and at the end of the clamp. RESULTS: Acute hyperinsulinemia
      induced by the euglycemic hyperinsulinemic clamp reduced the levels of TNF-alpha,
      IL-8, IL-10 and IL-18 in healthy controls but not in the offspring of type 2
      diabetic subjects having NGT or IGT. In response to insulin, levels of hs-CRP
      decreased and levels of IL-6 increased significantly in all study groups. The
      levels of adhesion molecules (ICAM-1, VCAM-1, E-Selectin) remained unchanged in
      response to hyperinsulinemia. CONCLUSIONS: The suppression of cytokine levels
      (particularly proinflammatory cytokines) during acute hyperinsulinemia observed
      in healthy controls was not present in offspring of type 2 diabetic patients.
      This emphasizes the crucial role of low-grade inflammation in insulin resistance
      in subjects with high risk of developing diabetes.

PMID- 20031128
TI  - Cardiorespiratory fitness modifies the association between the UCP3-55C>T
      (rs1800849) polymorphism and plasma homocysteine in Swedish youth.
AB  - OBJECTIVE: Whether the polymorphisms in the UCP3 gene have an influence on plasma
      homocysteine levels during youth is not known, and to elucidate the putative
      modifying role of fitness is also of clinical interest. We analysed the
      association between polymorphisms in the UCP3 gene and plasma homocysteine in
      youth and to examine whether fitness modifies this association. METHODS: The
      study population comprised 267 Swedish children (8-10 years) and 305 adolescents
      (14-16 years). Fasting total plasma homocysteine was the outcome variable. We
      genotyped five UCP3 polymorphisms (rs1800849, rs1800006, rs2075577, rs647126, and
      rs591758) and one MTHFR 677C>T (rs1801133) polymorphism. Cardiorespiratory
      fitness was measured with a maximal ergometer bike test. RESULTS: Youth
      homozygous or heterozygous for the T allele of the rs1800849 polymorphism had
      significantly higher levels of homocysteine than those carrying the CC genotype
      (8.56+/-4.72 micromol/L vs. 7.72+/-2.73 micromol/L, respectively, P=0.011) after
      adjusting for gender, age, pubertal status, folate and vitamin B(12) intake and
      MTHFR 677C>T polymorphism, whereas no association was observed for the other
      analysed polymorphisms. There was a significant interaction effect of
      fitnessxrs1800849 polymorphism (P=0.042). The effect of the rs1800849
      polymorphism on homocysteine levels persisted in youth with low fitness, whereas
      it was abolished in those with moderate or high cardiorespiratory fitness
      (P>0.1). CONCLUSIONS: Cardiorespiratory fitness modifies the association between
      the rs1800849 polymorphism and homocysteine so that the negative effect of the T
      allele does not persist in youth with moderate to high levels of fitness.

PMID- 20031129
TI  - Anaemia, independent of chronic kidney disease, predicts all-cause and
      cardiovascular mortality in type 2 diabetic patients.
AB  - OBJECTIVE: There is limited and controversial information on whether anaemia is a
      risk factor for cardiovascular mortality in type 2 diabetes, and whether this
      risk is modified by the presence of chronic kidney disease (CKD). We assessed the
      predictive role of lower hemoglobin concentrations on all-cause and
      cardiovascular mortality in a cohort of type 2 diabetic individuals. METHODS: The
      cohort included 1153 type 2 diabetic outpatients, who were followed for a mean
      period of 4.9 years. The independent association of anaemia (i.e., hemoglobin
      <120 g/l in women and <130 g/l in men) with all-cause and cardiovascular
      mortality was evaluated by Cox proportional hazards regression models and
      adjusted for several potential confounders, including kidney function measures.
      RESULTS: During follow-up, 166 (14.4%) patients died, 42.2% (n=70) of them from
      cardiovascular causes. In univariate analysis, anaemia was associated with
      increased risk of all-cause (hazard ratio HR 2.62, 95% confidence intervals 1.90
      3.60, p<0.001) and cardiovascular mortality (HR 2.70, 1.67-4.37, p<0.001). After
      adjustment for age, sex, body mass index, smoking, hypertension, dyslipidemia,
      diabetes duration, hemoglobin A1c, medication use (hypoglycemic, anti
      hypertensive, lipid-lowering and anti-platelet drugs) and kidney function
      measures, the association of anaemia with all-cause (adjusted HR 2.11, 1.32-3.35,
      p=0.002) and cardiovascular mortality (adjusted HR 2.23, 1.12-4.39, p=0.020)
      remained statistically significant. CONCLUSIONS: Anaemia is associated with
      increased risk of all-cause and cardiovascular mortality in type 2 diabetic
      individuals, independently of the presence of CKD and other potential
      confounders. The advantage to treat anaemia in type 2 diabetes for reducing the
      risk of adverse cardiovascular outcomes remains to be demonstrated.

PMID- 20031130
TI  - Serum low-density lipoprotein cholesterol level is strong risk factor for
      acquired color vision impairment in young to middle-aged Japanese men: the Okubo
      Color Study Report 2.
AB  - OBJECTIVE: To investigate associations between blood low-density lipoprotein
      cholesterol (LDL-C) levels and the prevalence of acquired color vision impairment
      (ACVI) in middle-aged Japanese men. METHODS: Participants in this cross-sectional
      study underwent color vision testing, ophthalmic examination, a standardized
      interview and examination of venous blood samples. Ishihara plates, a Lanthony 15
      hue desaturated panel, and Standard pseudoisochromatic Plates part 2 were used to
      examine color vision ability. The Farnsworth-Munsell 100-hue test was performed
      to define ACVI. Smoking status and alcohol intake were recorded during the
      interview. We performed logistic regression analysis adjusted for age, LDL-C
      level, systemic hypertension, diabetes, cataract, glaucoma, overweight, smoking
      status, and alcohol intake. Adjusted odds ratios for four LDL-C levels were
      calculated. RESULTS: A total of 1042 men were enrolled, 872 participants were
      eligible for the study, and 31 subjects were diagnosed with ACVI. As compared to
      the lowest LDL-C category level (<100 mg/dl), the crude OR of ACVI was 3.85 (95%
      confidence interval [CI], 1.24-11.00) for the 2nd highest category (130-159
      mg/dl), and 4.84 (95% CI, 1.42-16.43) for the highest level (>or=160 mg/dl). The
      multiple-adjusted ORs were 2.91 (95% CI, 0.87-9.70) for the 2nd highest category
      and 3.81 (95% CI, 1.03-14.05) for the highest level. Tests for trend were
      significant (P<0.05) in both analyses. CONCLUSIONS: These findings suggested that
      the prevalence of ACVI is higher among middle-aged Japanese men with elevated LDL
      C levels. These changes might be related to deteriorated neurologic function
      associated with lipid metabolite abnormalities.

PMID- 20031131
TI  - Postprandial metabolic and hormonal responses of obese dyslipidemic subjects with
      metabolic syndrome to test meals, rich in carbohydrate, fat or protein.
AB  - BACKGROUND: The metabolic syndrome (MS) is a cluster of heterogeneous
      abnormalities conferring increased risk of cardiovascular diseases. Few
      postprandial studies have been conducted in MS individuals. OBJECTIVES: We aimed
      to study MS subjects with the same abnormalities: abdominal obesity,
      hypertriglyceridemia and low plasma HDL. We assessed postprandial variations of
      metabolic parameters related to obesity, dyslipidemia and glucose homeostasis.
      METHODS: In this randomized, double-blind, cross-over study, male MS and control
      subjects consumed, at separate occasions, a high carbohydrate (HC), high fat (HF)
      or high protein (HP) breakfast meal providing 30% of each subject's resting
      energy expenditure. RESULTS: Appetite hormones peptide YY and ghrelin did not
      differ between-subject groups. Interleukin-6 was two-fold higher in MS compared
      with control subjects, consistently with an inflammatory state.
      Hypertriglyceridemia of MS subjects was aggravated postprandially with the HF and
      HP meals and was lowest after the HC meal, arguing against increased hepatic VLDL
      production. HDL-cholesterol of MS subjects remained low postprandially, whereas
      apolipoprotein (apo) A-II was higher than in control subjects. Unexpectedly,
      postprandial insulin and glucose responses were higher in MS compared with
      control subjects, with the HP meal inducing the greater effects. CONCLUSIONS: The
      sustained postprandial hypertriglyceridemia of MS subjects after all meals
      suggests defective catabolism of triglyceride-rich lipoproteins. The greater
      postprandial increases in plasma insulin and glucose in MS relatively to control
      subjects indicate decreased insulin sensitivity, not revealed in the fasted
      state.

PMID- 20031133
TI  - Epicardial adipose tissue and coronary artery plaque characteristics.
AB  - OBJECTIVE: Epicardial adipose tissue (EAT) has been implicated in the
      pathogenesis of coronary atherosclerosis. The association of EAT volume with type
      of coronary artery plaque on computed tomography angiography (CTA) is not known.
      METHODS: Coronary artery calcium (CAC) scoring and EAT volume measurement were
      performed on 214 consecutive patients (mean age 54+/-14 years) referred for
      coronary CTA. CAC was performed on non-contrast images, while EAT volume, the
      severity of luminal stenoses, and plaque characterization were assessed using
      contrast-enhanced CTA images. EAT volume was also indexed to body surface area
      (EAT-i). RESULTS: EAT volume correlated with age, height, body mass index (BMI),
      and CAC score. EAT volume increased significantly with the severity of luminal
      stenosis (p<0.001), and in patients with no plaques, calcified, mixed, and non
      calcified plaques (62+/-33mL, 63+/-22mL, 98+/-47mL, and 99+/-36mL, respectively,
      p<0.001). The EAT volume was significantly larger in patients with mixed or non
      calcified plaques compared to patients with calcified plaques or no plaques (all
      p<0.01 or smaller). The trend remained significant after adjustment for
      traditional risk factors for coronary artery disease. In adjusted models EAT was
      an independent predictor of CAC [exp(B)=3.916, p<0.05], atherosclerotic plaques
      of any type [exp(B)=4.532, p<0.01], non-calcified plaques [exp(B)=3.849, p<0.01],
      and obstructive CAD [exp(B)=3.824, p<0.05]. The above results were unchanged
      after replacing EAT with EAT-i. CONCLUSION: EAT volume was larger in the presence
      of obstructive CAD and non-calcified plaques. These data suggest that EAT is
      associated with the development of coronary atherosclerosis and potentially the
      most dangerous types of plaques.

PMID- 20031132
TI  - Association of apolipoprotein M with high-density lipoprotein kinetics in
      overweight-obese men.
AB  - OBJECTIVE: The aim of this study was to investigate associations between plasma
      apoM concentration and HDL apoA-I and apoA-II kinetics in 60 overweight-obese,
      insulin resistant men. METHODS: Plasma apoM concentration was determined using a
      sandwich ELISA with two monoclonal antibodies (CV<5%). The kinetics of HDL apoA-I
      and apoA-II were measured using intravenous administration of D(3)-leucine, gas
      chromatography-mass spectrometry and multi-compartmental modeling. RESULTS:
      Plasma apoM was inversely associated with body mass index and positively
      associated with plasma total cholesterol, LDL cholesterol and HDL cholesterol
      (p<0.05). There were no associations between plasma apoM and plasma triglyceride,
      NEFA, insulin, glucose, HOMA score or adiponectin concentrations. Plasma apoM was
      positively associated with both apoA-I and apoA-II concentrations (r=0.406,
      p<0.01 and r=0.510, p<0.01, respectively) and negatively associated with HDL apoA
      I and apoA-II fractional catabolic rate (FCR) (r=-0.291, p=0.03 and r=-0.291,
      p=0.026, respectively). No significant associations were observed between plasma
      apoM and HDL apoA-I and apoA-II production rate. In multivariate regression
      models, both plasma apoM and triglycerides were significant, independent
      predictors of HDL apoA-I FCR (adjusted R(2)=16%, p<0.01) and HDL apoA-II FCR
      (adjusted R(2)=14%, p<0.01). CONCLUSION: ApoM may be a significant, independent
      predictor of HDL apoA-I and apoA-II catabolism in overweight-obese, insulin
      resistant men.

PMID- 20031134
TI  - The natural history of aortic atherosclerosis: a systematic histopathological
      evaluation of the peri-renal region.
AB  - BACKGROUND: Risk factor profiles for the different vascular beds (i.e. coronary,
      carotid, peripheral and aortic) are remarkably different, suggesting that
      atherosclerosis is a heterogeneous disorder. Little is known about the
      morphologic progression of atherosclerosis in the peri-renal aorta, one of the
      primary predilection sites of atherosclerosis. METHODS: A systematic analysis was
      performed in 260 consecutive peri-renal aortic patches (stained with Movat
      Pentachrome and H&E) collected during organ transplantation (mean donor age 46.5
      (range 5-76) years; 54% male symbol; mean BMI 24.9; 40% smokers; 20%
      hypertensive). Plaque morphology was classified according to the modified AHA
      classification scheme proposed by Virmani et al. [4]. Immunostaining against CD68
      was used to identify the distribution of intimal macrophages and monocytes in
      several predefined locations among various plaque types and fibrous cap
      thickness. RESULTS: There was significant intimal thickening (p<0.013) and medial
      thinning (p<0.032) with advancing age. The incidence of atherosclerotic plaques
      in the abdominal aorta correlated with age (r=0.640, p=0.01). During the first
      three decades of life adaptive intimal thickening and intimal xanthomas were the
      predominant lesions. In contrast, the fourth, fifth and sixth decades hallmarked
      more complicated plaques of pathological intimal thickening, early and late
      fibroatheromas (EFAs and LFAs), thin-cap FAs (TCFAs; cap thickness <155 microm),
      ruptured plaques (PRs), healed rupture and fibrotic calcified plaques. The mean
      percentage of lesional macrophages increased significantly from LFAs to TCFAs (5
      17%; p<0.001). Macrophage infiltration of the fibrous cap was negatively
      correlated with fibrous cap thickness (p<0.0004); TCFAs and PRs (caps<100 microm)
      contained significantly more macrophages (19%) compared with caps 101-300 microm
      (6%) and >300 microm (2%). Macrophages in shoulder regions were highest in early
      and late FAs ( approximately 45%) followed by TCFAs (27%) and PR (20%). Further,
      intimal vasa vasorum were mostly seen adjacent to the necrotic core of advanced
      atherosclerotic plaques and remained confined to the intimo-medial border despite
      marked thickening of the intima. CONCLUSION: This study shows that peri-renal
      aortic atherosclerosis starts early in life. Gross plaque morphologies of the
      peri-renal abdominal aorta are similar to coronary atherosclerosis yet
      indications were found for site specific differences in macrophage content and
      neovascularization.

PMID- 20031135
TI  - Parallel-plate fluid flow systems for bone cell stimulation.
AB  - Bone responds to changes in its mechanical environment, but the mechanisms by
      which it does so are poorly understood. One hypothesis of mechanosensing in bone
      states that osteocytes can sense the flow of fluid through the canalicular
      system. To study this in vitro a number of fluid flow devices have been designed
      in which cells are placed between parallel plates in sealed chambers. Fluid flows
      through the chambers at controlled rates, most commonly driven by a peristaltic
      pump. In addition to fluid flow, high pressures have been observed in these
      chambers, but the effect of this on the cellular responses has generally been
      ignored or considered irrelevant, something challenged by recent cellular
      experiments using pressure only. We have, therefore, devised a system in which we
      can considerably reduce the pressure while maintaining the flow rate to enable
      study of their effects individually and in combination. As reducing pressure also
      reduces the risk of leaks in flow chambers, our system is suitable for real-time
      microscopical experiments. We present details of the new systems and of
      experiments with osteoblasts to illustrate the effects of fluid flow with and
      without additional pressure on the translocation of beta-catenin to the nucleus.

PMID- 20031136
TI  - Structural behaviour and strain distribution of the long bones of the human lower
      limbs.
AB  - Although stiffness and strength of lower limb bones have been investigated in the
      past, information is not complete. While the femur has been extensively
      investigated, little information is available about the strain distribution in
      the tibia, and the fibula has not been tested in vitro. This study aimed at
      improving the understanding of the biomechanics of lower limb bones by: (i)
      measuring the stiffness and strain distributions of the different low limb bones;
      (ii) assessing the effect of viscoelasticity in whole bones within a
      physiological range of strain-rates; (iii) assessing the difference in the
      behaviour in relation to opposite directions of bending and torsion. The
      structural stiffness and strain distribution of paired femurs, tibias and fibulas
      from two donors were measured. Each region investigated of each bone was
      instrumented with 8-16 triaxial strain gauges (over 600 grids in total). Each
      bone was subjected to 6-12 different loading configurations. Tests were
      replicated at two different loading speeds covering the physiological range of
      strain-rates. Viscoelasticity did not have any pronounced effect on the
      structural stiffness and strain distribution, in the physiological range of
      loading rates explored in this study. The stiffness and strain distribution
      varied greatly between bone segments, but also between directions of loading.
      Different stiffness and strain distributions were observed when opposite
      directions of torque or opposite directions of bending (in the same plane) were
      applied. To our knowledge, this study represents the most extensive collection of
      whole-bone biomechanical properties of lower limb bones.

PMID- 20031137
TI  - Theoretical modeling of the interaction between alveoli during inflation and
      deflation in normal and diseased lungs.
AB  - Alveolar recruitment is a central strategy in the ventilation of patients with
      acute lung injury and other lung diseases associated with alveolar collapse and
      atelectasis. However, biomechanical insights into the opening and collapse of
      individual alveoli are still limited. A better understanding of alveolar
      recruitment and the interaction between alveoli in intact and injured lungs is of
      crucial relevance for the evaluation of the potential efficacy of ventilation
      strategies. We simulated human alveolar biomechanics in normal and injured lungs.
      We used a basic simulation model for the biomechanical behavior of virtual single
      alveoli to compute parameterized pressure-volume curves. Based on these curves,
      we analyzed the interaction and stability in a system composed of two alveoli. We
      introduced different values for surface tension and tissue properties to simulate
      different forms of lung injury. The data obtained predict that alveoli with
      identical properties can coexist with both different volumes and with equal
      volumes depending on the pressure. Alveoli in injured lungs with increased
      surface tension will collapse at normal breathing pressures. However, recruitment
      maneuvers and positive endexpiratory pressure can stabilize those alveoli, but
      coexisting unaffected alveoli might be overdistended. In injured alveoli with
      reduced compliance collapse is less likely, alveoli are expected to remain open,
      but with a smaller volume. Expanding them to normal size would overdistend
      coexisting unaffected alveoli. The present simulation model yields novel insights
      into the interaction between alveoli and may thus increase our understanding of
      the prospects of recruitment maneuvers in different forms of lung injury.

PMID- 20031138
TI  - The challenges of the analysis of basic compounds by high performance liquid
      chromatography: some possible approaches for improved separations.
AB  - This review considers some of the difficulties encountered with the analysis of
      ionised bases using reversed-phase chromatography, such as detrimental
      interaction with column silanol groups, and overloading which both lead to poor
      peak shapes. Methods of overcoming these problems in reversed-phase (RP)
      separations, by judicious selection of the column and mobile phase conditions,
      are discussed. Hydrophilic interaction chromatography is considered as an
      alternative method for the separation of some basic compounds.

PMID- 20031140
TI  - Development of a microbioreactor with ecto-nucleoside triphosphate
      diphosphohydrolase 2 (NTPDase2) immobilized on a polyacrylamide-coated capillary
      at the outlet.
AB  - A simple and fast method of immobilization of cell membrane suspension containing
      human ecto-nucleoside triphosphate diphosphohydrolase 2 (NTPDase2) on a
      polyacrylamide-coated capillary was developed. The enzyme microbioreactor was
      prepared by hydrodynamic injection of a small plug of the polycationic
      electrolyte hexadimethrine bromide (HDB) followed by a suspension of an enzyme
      containing membrane preparation. In order to shorten the enzyme assay time and to
      increase the throughput of the assay, the capillary was coated from the outlet
      end and all injections were performed from the outlet end of the capillary. For
      the monitoring of the enzymatic reaction, the substrate ATP dissolved in reaction
      buffer (140 mM NaCl, 5mM KCl, 1mM MgCl(2), 2mM CaCl(2), and 10mM Hepes, pH 7.4,
      internal standard: 10 microM UMP) in the absence or presence of inhibitor was
      injected electrokinetically and incubated in the microbioreactor for 1 min with 1
      kV of applied voltage. Then, the electrophoretic separation of the reaction
      products was initiated by applying a constant current of 60 microA. A 50mM
      phosphate buffer (pH 6.5) was used for the separations and the products were
      detected by UV absorbance at 260 nm. The new method was compared with an at
      capillary-inlet method without immobilization of the enzyme. The results (K(m)
      values, K(i) values for inhibitor) obtained with both methods were similar and
      comparable with literature data. The developed outlet immobilized enzyme
      microreactor using a coated capillary is very fast, simple and most economic
      allowing multiple use of the enzyme.

PMID- 20031139
TI  - Surfactant-bound monolithic columns for separation of proteins in capillary high
      performance liquid chromatography.
AB  - A surfactant-bound monolithic stationary phase based on the co-polymerization of
      11-acrylamino-undecanoic acid (AAUA) is designed for capillary high performance
      liquid chromatography (HPLC). Using D-optimal design, the effect of the
      polymerization mixture (concentrations of monomer, crosslinker and porogens) on
      the chromatographic performance (resolution and analysis time) of the AAUA-EDMA
      monolithic column was evaluated. The polymerization mixture was optimized using
      three proteins as model test solutes. The D-optimal design indicates a strong
      dependence of chromatographic parameters on the concentration of porogens (1,4
      butanediol and water) in the polymerization mixture. Optimized solutions for fast
      separation and high resolution separation, respectively, were obtained using the
      proposed multivariate optimization. Differences less than 6.8% between the
      predicted and the experimental values in terms of resolution and retention time
      indeed confirmed that the proposed approach is practical. Using the optimized
      column, fast separation of proteins could be obtained in 2.5 min, and a tryptic
      digest of myoglobin was successfully separated on the high resolution column. The
      physical properties (i.e., morphology, porosity and permeability) of the
      optimized monolithic column were thoroughly investigated. It appears that this
      surfactant-bound monolith may have a great potential as a new generation of
      capillary HPLC stationary phase.

PMID- 20031141
TI  - Simultaneous determination of acidic, neutral and basic pharmaceuticals in urban
      wastewater by ultra high-pressure liquid chromatography-tandem mass spectrometry.
AB  - In this work, an ultra high-pressure liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) method has been developed for the simultaneous
      quantification and confirmation of the 20 most consumed pharmaceuticals in Spain
      in urban wastewater and surface water samples. The scope of the method included
      acidic, neutral and basic compounds belonging to different therapeutic classes
      and allows their simultaneous determination in just a single injection, giving
      realistic information of the most widely consumed pharmaceuticals in only one
      analysis. An enrichment step based on solid-phase extraction using Oasis HLB
      cartridges was carried out, followed by UHPLC-MS/MS measurement with a fast
      acquisition triple quadrupole mass analyzer. It allowed working with short dwell
      times and made possible to acquire three simultaneous SRM transitions per
      compound to assure a reliable identification. Several isotope-labelled internal
      standards were used as surrogates to correct SPE losses, as well as matrix
      effects that notably affect quantification of analytes. The method was validated
      in surface water and effluent and influent urban wastewater at different
      concentrations from 0.005microg/L (surface water) to 1.25microg/L (influent
      wastewater). The optimized method was applied to the analysis of 84 urban
      wastewater samples (influent and effluent), with the result that 17 out of 20
      compounds monitored were detected in the samples. Analgesics and anti
      inflamatories, cholesterol lowering statin drugs and lipid regulators were the
      major groups found, with diclofenac, ketoprofen, naproxen, 4-aminoantipyrine,
      bezafibrate, gemfibrozil and venlafaxine being the most frequently detected. The
      highest concentration level reached was 277microg/L for salicylic acid in
      influent wastewater.

PMID- 20031142
TI  - Determination of the interparticle void volume in packed beds via intraparticle
      Donnan exclusion.
AB  - Interparticle void volumes and porosities of packed capillaries have been
      determined using intraparticle Donnan exclusion of a small, unretained, co-ionic
      tracer (nitrate ions). The operational domain of this approach has been
      characterized for bare silica, reversed-phase, and strong cation-exchange
      materials (with different particle sizes and intraparticle pore sizes) in
      dependence of the mobile phase ionic strength. Interparticle porosities agree
      well with those analyzed by inverse size-exclusion chromatography (ISEC).
      Limitations to the use of Donnan exclusion (electrostatic exclusion) and ISEC
      (mechanical exclusion) arise as either type of exclusion becomes noticeable also
      in the cusp regions between the particles, or as the intraparticle pores are so
      large that complete electrostatic and size-exclusion are difficult to realize.
      Our data confirm that intraparticle Donnan exclusion presents a most simple,
      fast, and reliable approach for the analysis of packing densities.

PMID- 20031143
TI  - Solid-phase microextraction in bioanalysis: New devices and directions.
AB  - The primary objective of this review is to discuss recent technological
      developments in the field of solid-phase microextraction that have enhanced the
      utility of this sample preparation technique in the field of bioanalysis. These
      developments include introduction of various new biocompatible coating phases
      suitable for bioanalysis, such as commercial prototype in vivo SPME devices, as
      well as the development of sampling interfaces that extend the use of this
      methodology to small animals such as mice. These new devices permit application
      of in vivo SPME to a variety of analyses, including pharmacokinetics,
      bioaccumulation and metabolomics studies, with good temporal and spatial
      resolution. New calibration approaches have also been introduced to facilitate in
      vivo studies and provide fast and quantitative results without the need to
      achieve equilibrium. In combination with the drastic improvement in the
      analytical sensitivity of modern liquid chromatography-tandem mass spectrometry
      instrumentation, full potential of in vivo SPME as a sample preparation tool in
      life sciences can finally be explored. From the instrumentation perspective, SPME
      was successfully automated in 96-well format for the first time. This opens up
      new opportunities for high-throughput applications (>1000 samples/day) such as
      for the determination of unbound and total drug concentrations in complex
      matrices such as whole blood with no need for sample pretreatment, studies of
      distribution of drugs in various compartments and/or determination of plasma
      protein binding and other ligand-receptor binding studies, and this review will
      summarize the progress in this research area to date.

PMID- 20031144
TI  - Ganoderma species discrimination by dual-mode chromatographic fingerprinting: a
      study on stationary phase effects in hydrophilic interaction chromatography and
      reduction of sample misclassification rate by additional use of reversed-phase
      chromatography.
AB  - Acetonitrile-water extracts of several Ganoderma species - a mushroom being used
      in Traditional Chinese Medicine - were analysed by liquid chromatography-UV
      detection in hydrophilic interaction chromatography (HILIC) and reversed-phase
      (RP) elution modes. A set of six polar stationary phases was used for HILIC runs.
      These columns had remarkably different separation properties under binary
      gradient conditions as evinced by hierarchical cluster analysis on retention
      patterns of seven test compounds. Complementary measurements of RP chromatograms
      were carried out on a C(18) packing. Injection precision (n=5) and intra-day
      precision (n=5) were each <2.0% RSD (HILIC) and <0.7% RSD (RP) for relative
      retention times of main characteristic peaks of a sample extract while for
      relative peak areas RSD values were max. 6.8%. Repetitive analysis (n=7) of a
      processed sample stored in the autosampler tray for 48h was used to confirm
      within-sequence sample stability. Eleven Ganoderma lucidum samples served as
      training set for the construction of column-specific simulated mean
      chromatograms. Validation with twelve samples comprising G. lucidum, Ganoderma
      sinense, Ganoderma atrum, and Ganoderma tsugae by correlation coefficient based
      similarity evaluation of peak patterns showed that a discrimination of G. lucidum
      from other Ganoderma species by means of chromatographic fingerprints is
      conceptually possible on all columns, except of a bare silica packing. The
      importance of the combined use of RP and HILIC fingerprints to improve the rate
      of correct sample classification was demonstrated by the fact that each one G.
      sinense specimen was wrongly assigned being G. lucidum by all HILIC fingerprints
      but not the RP fingerprint and vice versa. The present data revealed that (i) the
      analysis of complex biological materials by quasi orthogonal chromatographic
      modes such as HILIC and RP may deliver more discriminative information than
      single-mode approaches which strengthens the reliability of fingerprint-based
      sample classification and (ii) different retention and selectivity
      characteristics of polar bonded silica packings in the HILIC elution mode may
      only have a minor impact on chemometric sample discrimination capabilities in
      such kind of pattern-oriented metabolomics separation problems.

PMID- 20031145
TI  - Enantiomeric separation of chiral polycyclic musks by capillary electrophoresis:
      Application to the analysis of cosmetic samples.
AB  - The enantiomeric separation of four chiral polycyclic musks (Galaxolide,
      Tonalide, Traseolide and Phantolide) using CE was achieved for the first time in
      this work. Two chiral methodologies were developed by CD-MEKC using SDS as
      surfactant in a CHES buffer (pH 9.0). One methodology enabled the fast
      enantiomeric separation of individual polycyclic musks with analysis times lower
      than 10min for Tonalide, 13min for Traseolide and Phantolide, and 17min for
      Galaxolide. Enantiomeric resolutions obtained were higher than 1.5 using
      different separation media for each compound. A second methodology was also
      developed enabling the simultaneous enantioseparation of the four musks. In this
      case, the use of a dual CD system containing two neutral CDs was necessary to
      achieve the separation of all enantiomers from three out of four musks in 45min.
      Although a coelution between Galaxolide and Phantolide was observed, the use of
      different UV absorption wavelengths allowed the simultaneous analysis of both
      musks. In addition, a sweeping strategy was performed in order to increase the
      sensitivity of the method. Appropriate analytical characteristics (linearity, LOD
      and LOQ, precision and absence of matrix interferences) were obtained for
      conventional and sweeping methodologies. Finally, the usefulness of the method
      was demonstrated in the determination of the enantiomers of the polycyclic musks
      in personal care products as perfumes.

PMID- 20031146
TI  - Mesoporous zirconium phosphate from yeast biotemplate.
AB  - Mesoporous zirconium phosphate has attracted increasing interest due to its
      extraordinary functionalities. In particular, great progress has been made in the
      synthesis of mesoporous zirconium phosphate using traditional approaches.
      However, synthesis of mesoporous zirconium phosphate using yeast as biotemplate
      has not been well studied so far. Here, we show that zirconium phosphate with a
      mesoporous structure has been synthesized under ambient conditions using yeast as
      biotemplate. The derived samples were examined by X-ray diffraction (XRD), energy
      dispersive X-ray analysis (EDX), transmission electron microscopy (TEM),
      thermogravimetry/differential thermal analysis (TG/DTA), fourier transform
      infrared spectroscopy (FTIR), and N(2) adsorption-desorption isotherms. A
      biotemplated mesoporous zirconium phosphate, possessing a specific surface area
      (Brunauer-Emmett-Teller, BET) of 217.64 m(2) g(-1), a narrow pore distribution
      centered at 2.7 nm, and pore volume of 0.24 cm(3) g(-1), was obtained. We
      discover that amide carboxyl groups of yeast play an important role in the
      chemical interaction between protein molecules and zirconium phosphate
      nanoparticles. Interestingly, an air electrode fabricated using mesoporous
      zirconium phosphate exhibits remarkable electrocatalytic activity for oxygen
      reduction reaction (ORR), compared to that of the electrolytic manganese dioxide
      (EMD) air electrode employed commercially, which has important applications in
      fuel cell technologies.

PMID- 20031147
TI  - Oxide surface modification: synthesis and characterization of zirconia-coated
      alumina.
AB  - Four aluminas were used as supports for impregnation with a zirconium oxide with
      the aim to achieve a coating, without phase separation, between support and
      modifier. The supports were impregnated with different concentrations of
      zirconium aqueous resin, obtained through the polymeric precursor method. After
      impregnation the samples were calcined and then characterized by XRD, which led
      to identification of crystalline zirconia in different concentrations from each
      support used. Using a simple geometric model the maximum amount of surface
      modifier oxide required for the complete coating of a support with a layer of
      unit cells was estimated. According to this estimate, only the support should be
      identified below the limit proposed and crystalline zirconium oxide should be
      identified above this limit when a complete coating is reached. The results
      obtained from XRD agree with the estimated values and to confirm the coating, the
      samples were also characterized by EDS/STEM, HRTEM, XPS, and XAS. The results
      showed that the zirconium oxide on the surface of alumina support reached the
      coating in the limit of 15 Zr nm(-2), without the formation of the ZrO(2) phase.

PMID- 20031148
TI  - Polymerizable gemini surfactants at solid/solution interfaces: adsorption and
      polymerization on melamine formaldehyde particles and capsule fabrication.
AB  - Organic capsules have been fabricated via three steps, by using the polymerizable
      gemini surfactant (1,2-bis(dimethyl(11-methacryloyloxy)undecylammonio) hexane
      dibromide, PC11-6-11) as a single wall component. In the first fabrication step,
      the surfactant spontaneously adsorbs on acid-dissolvable melamine formaldehyde
      (MF) particles in aqueous media. The adsorption isotherm data reveal that the
      adsorbed amount of PC11-6-11 (per chain) is greater than that of the
      corresponding monomeric surfactant ((11-methacryloyloxy)undecyltrimethylammonium
      bromide, PC11), resulting from the greater intermolecular association of PC11-6
      11 at the solid/solution interface. The closely packed adsorbed layer of PC11-6
      11 provides an opportunity to give a polymer thin film, as a result of in situ
      photo-polymerization on MF particles (in the second fabrication step) and
      subsequent acid dissolution of the core MF particles (in the third fabrication
      step). The dynamic light scattering (DLS) measurements have shown that the
      apparent hydrodynamic diameter of PC11-6-11 capsules is reversibly changed in
      response to a change in ionic strength: the increased background electrolyte
      concentration results in deswelling of the capsules, and vice versa. It seems
      likely that this swelling/deswelling behavior is primarily driven by the
      electrostatic interaction between quaternary ammonium groups within the
      polymerized film. We have also studied the capture and release capabilities of
      glucose into/from the capsule core and found that (i) glucose is encapsulated
      into the capsule core at high electrolyte concentrations and (ii) the glucose
      molecules encapsulated into the core are gradually released when the outer
      electrolyte solution is replaced by pure water. We believe, therefore, that the
      PC11-6-11 capsules fabricated here are useful as stimulus-responsive smart
      vehicles.

PMID- 20031149
TI  - Avalanches of coalescence events and local extensional flows--stabilisation or
      destabilisation due to surfactant.
AB  - From two-drop collision experiments, it is known that local extensional flow
      favors coalescence. Recently, Bremond et al. used microfluidic methods to
      evidence this point. Similarly, we used specific microfluidic geometries to
      impose sudden extensional flow, following drop collision under controlled
      conditions, and coalescence events were recorded with a high-speed camera. In
      this study we focus on the effect of surfactant on the coalescence, or
      stabilisation against it, between drops flowing apart due to either imposed
      external flow or capillary forces related to drop shape relaxation. Coalescence
      can be induced even when drops are initially separated by an intersticial
      lubricating film by far thicker than the critical thickness for rupturing under
      the action of Van der Waals forces. This is particularly relevant to avalanches
      of coalescence events, in flowing or even quiescent emulsions or foams. When non
      ionic surfactant was used, it was observed that small concentrations apparently
      enhance coalescence in extension. But at higher concentrations it provides
      stabilisation through a specific mechanism of thread formation and rupture; the
      stabilisation mechanism can be complex.

PMID- 20031150
TI  - Cement-epoxy/water interfaces--energetic, thermodynamic, and kinetic parameters
      by means of heat-conduction microcalorimetry.
AB  - Hydration phenomena at cement/water interfaces drive the characteristics of oil
      well cement slurries. In this study, new epoxy-modified cement slurries were
      synthesized. The slurries characterization has suggested the presence of low
      amounts of portlandite in the slurry with the higher content of polymerized epoxy
      resin. The hydration processes of the cement slurries were studied by heat
      conduction microcalorimetry. The energetic and enthalpic hydration data were all
      exothermic in nature. The cumulative heat release curves have shown the presence
      of multilinearity of the kinetic processes. The hydration microcalorimetric data
      were well fitted to the multistep Avrami kinetic model. It was found that the
      epoxy-modified cement slurries present a good potential to be used in
      environmental-friendly oil-well operations.

PMID- 20031151
TI  - A practical method for quantifying atherosclerotic lesions in rabbits.
AB  - The rabbit has been widely used for the study of human atherosclerosis; however,
      the method for analysis of the atherosclerotic lesions has not been standardized
      between laboratories. The present study reports a practical method for
      quantifying the changes that occur in aortic atherosclerosis of rabbits. Male
      Japanese white rabbits were fed with either a standard chow or a diet containing
      10% fat and 0.3% cholesterol for 16 weeks. Plasma concentrations of glucose,
      insulin, total cholesterol, triglycerides and high-density lipoprotein were
      measured. Aortic atherosclerotic lesions were assessed in quantitative fashion
      using an image analysis system that measured (1) the gross area of the entire
      aorta affected by atherosclerosis as defined by Sudan IV staining, (2) the
      microscopical intimal lesion defined by the elastic van Gieson stain and (3) the
      infiltration of macrophages and smooth muscle cell proliferation as determined
      immunohistochemically. The rabbits developed severe aortic atherosclerosis
      without apparent abnormality of glucose metabolism. The quantitative method
      described here will be useful for the further investigation of atherosclerosis in
      rabbits.

PMID- 20031152
TI  - Novel labels support 10-month-olds' attention to novel objects.
AB  - What is the source of the mutual exclusivity bias whereby infants map novel
      labels onto novel objects? In an intermodal preferential looking task, we found
      that novel labels support 10-month-olds' attention to a novel object over a
      familiar object. In contrast, familiar labels and a neutral phrase gradually
      reduced attention to a novel object. Markman (1989, 1990) argued that infants
      must recall the name of a familiar object to exclude it as the referent of a
      novel label. We argue that 10-month-olds' attention is guided by the novelty of
      objects and labels rather than knowledge of the names for familiar objects.
      Mutual exclusivity, as a language-specific bias, might emerge from a more general
      constraint on attention and learning.

PMID- 20031153
TI  - Rectal anatomy after rectopexy: cinedefecography versus MR-defecography.
AB  - BACKGROUND: Conventional defecography can reveal abnormalities in patients with
      evacuatory disorders. With fast dynamic MR imaging systems, MR-defecography has
      become possible, which does not expose patients to ionizing radiation. The
      purpose of this study was to assess the correlation of both methods after
      rectopexy. MATERIALS AND METHODS: Twenty-one consecutive patients underwent
      abdominal sigmoidectomy and rectopexy due to evacuatory disorders.
      Postoperatively, all patients were investigated by cineradiographic defecography.
      Fourteen patients underwent MR-defecography additionally. The results were
      screened for anorectal angle and pelvic floor position (rest, squeezing, and
      evacuation). The findings were depicted in Box plot analysis and compared with
      the Friedman-test. Descent of pelvic organs was also assessed. RESULTS: In MR
      defecography, anorectal angle at rest was smaller than in conventional
      defecography, but there was no difference during squeezing and defecation.
      Concerning pelvic floor position, during squeezing, MR-defecography illustrated a
      lower perineum and a broader range of pelvic settings, but no difference at rest
      and during evacuation. In four patients, MR-defecography visualized a descent of
      the bladder. However, in four patients with complete evacuation in
      cineradiography and with no clinical complaints about incomplete evacuation, MR
      imaging showed deficient evacuation. Overall continence of patients was
      significantly improved through surgery, but there was no change in sphincter
      pressure, radial asymmetry, or sphincter length. CONCLUSIONS: In general, with
      respect to anorectal angle and perineal motility, both methods revealed
      consistent results. The concomitant depiction of structures in MR-defecography is
      helpful in the assessment of descent of pelvic organs and permits visualization
      of enteroceles. However, in 30% of patients, MR-defecography wrongly showed
      incomplete evacuation.

PMID- 20031154
TI  - A novel hydrogel-coated polyester mesh prevents postsurgical adhesions in a rat
      model.
AB  - BACKGROUND: The specific aim of this study was to determine the whether a novel,
      hydrogel-coated polyester mesh (Scout) can be used to reduce the incidence and
      severity of adhesion formation in vivo. METHODS: An established rat model of post
      surgical adhesion formation was used in which adhesions are generated through
      surgical trauma to the surfaces of the cecum and the adjacent abdominal wall.
      Thirty-seven rats were randomly allocated either to a control group (no
      intervention; n=14 rats) or to one of two treatment groups in which the abraded
      surfaces were separated with either the Scout material (n=11 rats) or an FDA
      approved form of expanded polytetrafluorethylene (PTFE) (PRECLUDE Vessel Guard;
      n=12 rats). Animals were euthanized 7 d after surgery and gross necropsy
      examinations were performed. Mechanical testing was used to measure the strength
      of any adhesions that were identified, and histology was used to characterize
      within the adhesion tissue and on the surface(s) of the barrier materials.
      RESULTS: Five animals were excluded because of surgical failure (1 control; 2
      PRECLUDE Vessel Guard; 2 Scout). Adhesions were seen in 10 of 13 control animals
      (77%). There were no adhesions in any of the animals treated with either PRECLUDE
      Vessel Guard or Scout material. Histology demonstrated mild cellular adhesion to
      both the PRECLUDE Vessel Guard and the Scout material. Although there was a sub
      acute to chronic inflammatory response to the surgical trauma, there was no
      evidence of delamination, shearing, or degradation of either the Scout material
      or PRECLUDE Vessel Guard. CONCLUSIONS: The hydrogel-coated Scout material was as
      effective as the approved predicate material in this model. Both materials were
      well tolerated. Further testing of the Scout material is now warranted.

PMID- 20031155
TI  - Effectiveness of standardized clerkship teaching across multiple sites.
AB  - BACKGROUND: Surgical clerkship teaching for medical students at the University of
      Auckland is undertaken across multiple clinical campuses. Concerns are that
      differences in clinical experience may result in variability of learning outcome
      achievements. Our objectives were to investigate whether differences in clinical
      experience existed between teaching sites, and whether these differences
      correlate to differences in learning outcome achievements. Influence of clinical
      experience on future career choice was also explored. MATERIALS AND METHODS:
      Prospectively collected data were retrospectively reviewed. Clinical experience
      from assigned hospitals was collected using student Feedback Questionnaires and
      case history logbooks. Results were analyzed for inter-hospital differences. The
      Questionnaire included a question on influence of clinical experience on future
      career choice. A formative Objective Structured Clinical Examination (OSCE) was
      administered and results were analyzed for inter-hospital differences in learning
      outcome achievements. RESULTS: Feedback Questionnaires and case history logbooks
      identified inter-hospital differences in clinical experience. Clerkship enjoyment
      and involvement in theater correlated with increased likelihood of choosing a
      future surgical career. The OSCE had acceptable internal reliability (Cronbach's
      alpha 0.69-0.74) and strong correlations with other formal assessments,
      indicating its external validity. No significant inter-hospital differences in
      OSCE results were found after one-way analysis of variance comparison (P=0.125).
      CONCLUSION: Heterogeneity of clinical experience from multiple teaching sites did
      not translate into heterogeneity in achievement of learning outcomes when
      teaching and assessment materials were standardized. Clinical experience during
      undergraduate clerkships may influence future career choices. The OSCE is a
      validated and reliable tool for assessing student achievement of learning
      outcomes.

PMID- 20031156
TI  - Trends in pediatric appendectomy outcomes.

PMID- 20031157
TI  - Splanchnic Th(2) and Th(1) cytokine redistribution in microsurgical cholestatic
      rats.
AB  - BACKGROUND: Long-term extrahepatic cholestasis in the rat induces ductular
      proliferation and fibrosis in the liver, portal hypertension, splenomegaly,
      portosystemic collateral circulation, and ascites. These splanchnic alterations
      could have an inflammatory pathophysiology. MATERIAL AND METHODS: We measured
      serum levels of hepatobiliary injury markers and the acute phase proteins, alpha
      1-major acid protein (alpha(1)-MAP) and alpha-1-acid glycoprotein (alpha(1)-GPA)
      in rats 6 wk after microsurgical extrahepatic cholestasis. We also assayed Th(1)
      (TNF-alpha and IL-1beta) and Th(2) (IL-4 and IL-10) cytokine levels in the liver,
      ileum, spleen, and mesenteric lymph complex by enzyme-linked immunosorbent assay
      (ELISA) techniques. Liver fibrosis was measured by Sirius red stain and by using
      an image system computer-assisted method and mast cell liver infiltration by
      Giemsa stain. RESULTS: The cholestatic rats showed an increase (P<0.001) in serum
      levels of bile acids, total and direct bilirubin, AST, ALT, AST/ALT index, gamma
      GT, alkaline phosphatase, alpha(1)- MAP, alpha(1)-GPA, and LDH (P<0.05) in
      relation to sham-operated rats. TNF-alpha, IL-1beta, IL-4, and IL-10 increased in
      the ileum (P<0.01) and mesenteric lymph complex (P<0.001), and decreased in the
      liver (P<0.001). A marked bile proliferation associated with fibrosis (P<0.001)
      and mast cell infiltration was also shown in the liver of cholestatic rats.
      CONCLUSION: The splanchnic redistribution of cytokines, with an increase of Th(1)
      and Th(2) production in the small bowel and in the mesenteric lymph complex,
      supports the key role of inflammatory mechanisms in rats with secondary biliary
      fibrosis.

PMID- 20031158
TI  - Caveolin-1 regulating the invasion and expression of matrix metalloproteinase
      (MMPs) in pancreatic carcinoma cells.
AB  - The gelatinases B (MMP9) and A (MMP2) are two members of the matrix
      metalloproteinase (MMPs) family that are expressed in human cancer, and play a
      critical role in tumor cell invasion and metastasis. Caveolin-1 (Cav1) has
      recently been identified as a tumor metastasis modifier gene. However, the effect
      and mechanism of Cav1 in pancreatic carcinoma cell invasion remain unknown. In
      this study, we investigated the expression of Cav1, MMP2, and MMP9 in several
      different pancreatic carcinoma cell lines. We transfected pcDNA3.0-Cav1 plasmid
      and Cav1 siRNA into SW1990 and Bxpc3 cells, respectively. Using cell invasion
      assay, we found that overexpression of Cav1 inhibited cell invasion, whereas the
      knockdown of Cav1 in Bxpc3 cells promoted cell invasion. Moreover, to explore the
      mechanisms underlying these observations, we further investigated the expression
      of MMP2, MMP9, phospho-Akt, and phospho-Erk by Western blot, and the activities
      of MMP2 and MMP9 by gelatin zymography. The results indicated that Cav1 gene
      could inhibit pancreatic carcinoma cell invasion, at least in part, probably
      through Erk-MMP signal pathway, suggesting that the endogenous expression or re
      expression of Cav1 might help therapeutically reduce their invasive potential in
      pancreatic carcinoma cells.

PMID- 20031159
TI  - Autopsy after traumatic death--a shifting paradigm.
AB  - OBJECTIVE: The role of autopsy in evaluating missed injury after traumatic death
      is well established and discussed in the literature. The frequency of incidental
      findings in trauma patients has not been reported. We believe that incidental
      findings are under recognized and reported by trauma surgeons. PATIENTS AND
      METHODS: This prospective, descriptive, cohort study was conducted at a Level 1
      trauma center in a rural state. Four hundred ninety-six deaths over a 4-y period
      were identified from the trauma registry. Two hundred four complete autopsies
      were available for review. One thousand eighteen traumatic diagnoses were
      identified from 204 autopsies and corresponding medical records by trauma
      surgeons blinded to patient identity. The surgeons recorded missed diagnoses,
      incidental diagnoses identified at autopsy, and diagnoses known at the time of
      death confirmed by autopsy. RESULTS: The surgeons had a kappa-score of 0.82-0.84.
      Forty-two patients (21% of patients) had 68 severe missed injuries; 67 patients
      (33% of patients) had 94 minor missed injuries. Twenty-eight patients (14%) had
      significant incidental findings including premature atherosclerosis, multiple
      endocrine neoplasia, tuberculosis, and others. CONCLUSIONS: The autopsy after
      traumatic death is more than a mechanism of quality control and teaching. A high
      proportion of patients will have incidental findings important to family members,
      and have public health importance. Systems need to be developed to review autopsy
      results with attention to identifying and communicating incidental findings.
      Given the incidence of significant missed injuries and incidental findings, the
      autopsy continues to have an important role in health care.

PMID- 20031160
TI  - ZM336372 induces apoptosis associated with phosphorylation of GSK-3beta in
      pancreatic adenocarcinoma cell lines.
AB  - INTRODUCTION: ZM336372 is small molecule tyrosine kinase modulator. It has been
      shown to inhibit glycogen synthase kinase-3beta (GSK-3beta) through
      phosphorylation of GSK-3beta at Ser 9. GSK-3beta has previously been shown to
      mediate cell survival in pancreatic cancer cells. Here we determine the effects
      of ZM336372 on GSK-3beta phosphorylation, apoptosis, and growth in pancreatic
      adenocarcinoma cell lines. METHODS: Panc-1 and MiaPaCa-2 cells were treated with
      ZM336372 or lithium chloride (LiCl) and compared with solvent control. The
      effects on proliferation for each cell line were determined using the MTT assay.
      Western blot analysis was performed to examine the effects of treatment on the
      phosphorylation of GSK-3beta. In addition, western blot was utilized to examine
      the cleavage of poly (ADP-ribose) polymerase (PARP), a marker of apoptosis.
      RESULTS: A dose-dependent increase in phosphorylation of GSK-3beta was observed
      after treatment with both ZM336372 and LiCl. Growth inhibition due to treatment
      with ZM336372 and LiCl also occurred in a dose-dependent fashion. An increase in
      cleaved PARP was demonstrated after treatment with both agents, as was seen
      previously with GSK-3beta inhibition in pancreatic adenocarcinoma cells.
      CONCLUSION: This is the first description of growth inhibition and apoptosis in
      pancreatic cancer cells related to GSK-3beta inhibition through treatment with
      ZM336372.

PMID- 20031161
TI  - Comparisons of three surgical procedures on intestine ischemia reperfusion injury
      in a superior mesenteric artery injury model.
AB  - BACKGROUND: Temporary ligation, primary anastomosis, and temporary shunt have
      been reported to deal with superior mesenteric artery (SMA) injuries. We aimed to
      investigate which brought minimal ischemia reperfusion injury in a hypothermic
      traumatic shock swine model. METHODS: SMA was completely clamped while pigs were
      hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg. Animals were then
      randomized into temporary ligation (A, n=8), primary anastomosis (B, n=8),
      temporary shunt (C, n=8), and control groups (n=4). Animals in group A remained
      SMA interrupted for additional 1h while the other groups underwent the
      corresponding procedures immediately. Intestine injury was assessed by histologic
      examination and measurement of lipid peroxidations at the end of ischemia and
      experiment. RESULTS: Overall mortality rate was 50%, 25%, and 0% in groups A, B,
      and C, respectively (P<0.05). The total intestine ischemia time was predominantly
      shorter in group C in the other groups. Remarkable elevations of malonaldehyde
      (MDA) in small intestine were noted after reperfusion in group A. Animals in
      other groups, however, did not exacerbate during the 6-h reperfusion
      (resuscitation period). Group C showed the lowest MDA level at the end of
      experiment. Myeloperoxidase (MPO) levels showed no significant elevations during
      the ischemia or early reperfusion period; nevertheless, it reached approximately
      3- to 6-fold in groups A and B (compared with baseline, P<0.01), and remained
      unchanged in group C at the end of experiment. CONCLUSION: Our study suggests
      that temporary shunt insertion might be preferred as it shortens ischemia time,
      alleviates intestinal ischemia/reperfusion injury, and thus decreases early
      mortality in this animal model.

PMID- 20031162
TI  - Cancer therapy beyond apoptosis: autophagy and anoikis as mechanisms of cell
      death.
AB  - Apoptosis has long been recognized as a critical mechanism of programmed cell
      death that is preserved among all eukaryotes and is involved in a variety of
      disease processes. Malignant transformation of cells is associated with a
      constellation of pro-survival mutations rendering them resistant to apoptosis.
      Traditional cancer therapy evokes cell death by inducing apoptosis; however, the
      apoptotic resistance inherent in cancer cells has been a significant barrier to
      effective chemotherapy. More recently, other mechanisms of cell death have
      emerged as potential novel mechanisms for cancer therapies to induce cell death,
      either in addition to, or instead of, apoptosis-induced cytotoxic treatment.
      Autophagy is a process that occurs in all cells, but is induced in many types of
      cancer. Autophagy functions as both a cell survival and a cell death mechanism
      depending on the context and the stimuli, which are likely exploitable for cancer
      therapy. Anoikis is also a physiologic process in normal cells used to maintain
      homeostasis, in which cell death is induced in response to loss of extracellular
      membrane (ECM) attachment. Cancer cells are notoriously resistant to anoikis,
      enabling metastasis and new tumor growth beyond their original environment.
      Interestingly, autophagy may actually by a major contributor to anoikis
      resistance in cancer. As these two processes are elucidated in more detail, there
      is great potential for novel targets that affect cancer cell death, in addition
      to the current cytotoxic agents.

PMID- 20031163
TI  - Remote thermal injury increases LPS-induced intestinal IL-6 production.
AB  - BACKGROUND: Patients suffering from burn injury are at high risk for subsequent
      infection. Thermal injury followed by endotoxemia may result in a "second hit,"
      causing an exaggerated inflammatory response with increased morbidity and
      mortality. The role of the intestine in this "second hit" response is unknown. We
      hypothesized that remote thermal injury increases the inflammatory response of
      intestinal mucosa to subsequent treatment with lipopolysaccharide (LPS). METHODS:
      Mice underwent sham or scald injury. Seven days after injury, mice were treated
      with LPS. Blood and bowel specimens were obtained. Serum and intestinal
      inflammatory cytokines were measured by enzyme-linked immunosorbent assay
      (ELISA). Changes in TLR-4 pathway components in intestine were measured by
      reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and
      electrophoretic mobility shift assay (EMSA). Intestinal leukocyte infiltration
      was analyzed by myeloperoxidase assay. RESULTS: A "second hit" of injected LPS
      resulted in increased IL-6 in intestine of burned mice compared with sham.
      Similarly, jejunal IL-6 mRNA levels increased in mice with prior thermal injury,
      suggesting a transcriptional mechanism. Of transcription factors known to drive
      IL-6 expression, only AP-1 activation was significantly elevated by a "second
      hit" of LPS. CONCLUSION: Prior thermal injury potentiates LPS-induced IL-6
      cytokine production in intestine. These results indicate a heightened
      inflammatory response to a second hit by intestine after burn injury.

PMID- 20031164
TI  - Clinical significance of immunohistochemically-identified lymphatic and/or blood
      vessel tumor invasion in gastric cancer.
AB  - BACKGROUND: Tumor invasion and lymph node metastasis are significant prognostic
      factors for gastric cancer, and lymphatic and vascular tumor invasion are also
      significant risk factors for gastric cancer recurrence. Recently, the
      immunohistochemical detection of lymphatic and blood vessel tumor invasion (LBVI)
      has been shown to have a higher sensitivity and specificity than hematoxylin
      eosin staining methods. MATERIALS AND METHODS: One hundred forty-nine gastric
      cancer patients who underwent curative resection at Korea University Hospital
      between November 2003 and December 2006 served as the study subjects. Lymphatic
      vessel invasion was evaluated by immunostaining with the new selective marker, D2
      40, and blood vessel invasion was assessed with anti-CD31 antibody. Patients were
      divided according to the presence of LBVI, clinicopathologic factors were
      compared, and postoperative surgical outcomes were analyzed. RESULTS: LBVI was
      present in 66 patients (44.3%). LBVI was significantly correlated with depth of
      tumor invasion (P < 0.001), lymph node stage (P < 0.001), and lymph node
      micrometastasis (P = 0.013). Cancer recurrence was more common in the LBVI group
      (P = 0.007), and peritoneal seeding was the most prevalent type of recurrence (P
      = 0.028). Univariate analysis showed tumor size, depth of tumor invasion, lymph
      node stage, and LBVI to have a significant impact on survival. Based on
      multivariate analysis, however, depth of tumor invasion and lymph node stage were
      correlated with survival. CONCLUSION: Immunohistochemical demonstration of LBVI
      is an additional prognostic marker, and provides useful information for planning
      treatment strategies in gastric cancer patients.

PMID- 20031165
TI  - Early blood biomarkers predict organ injury and resource utilization following
      complex cardiac surgery.
AB  - BACKGROUND: Patients undergoing complex cardiac surgery (thoracic aorta and
      valve) are at risk for organ failure and increased resource utilization.
      Neutrophil gelatinase-associated lipocalin (NGAL) has been found to be an early
      biomarker for renal injury. Multiplex cytokine immunoassays allow the evaluation
      of the early inflammatory response. We examined the relationship between early
      biomarker appearance (NGAL and multiplex cytokines) and organ injury and resource
      utilization. MATERIALS AND METHODS: NGAL and multiplex cytokine immunoassays were
      performed at baseline, 1, 6, and 24 h following surgery on 38 patients undergoing
      thoracic aorta and valve operations. The mean age was 65 y with 26 males and 12
      females. Acute kidney injury (AKIN definition), pulmonary failure (>24 h
      ventilation), and intensive care unit and hospital stays were examined. RESULTS:
      One hour following complex cardiac surgery, the quartile of patients with the
      greatest IL-6 response had higher serum NGAL levels compared with the lowest
      quartile (347 versus 145 ng/mL, P=0.002), and 70% of these patients progressed to
      clinical kidney injury. Six hours following surgery, the quartile of patients
      with the greatest IL-10 response had higher serum NGAL compared with the lowest
      quartile (271 versus 160, P =0.04), more pulmonary failure (60% versus 10%, P
      =0.01), and longer ICU and hospital stays (P =0.001). CONCLUSIONS: Patients with
      early elevated biomarkers of inflammation exhibited higher NGAL, more pulmonary
      failure, and greater resource utilization. Earlier identification of patients at
      risk for organ injury may allow for earlier intervention and reduce resource
      utilization.

PMID- 20031166
TI  - Pterostilbene inhibits lung cancer through induction of apoptosis.
AB  - BACKGROUND: Lung cancer remains the leading cause of cancer mortality in the
      United States. Resveratrol is a potent antioxidant found in grapes that inhibits
      several types of cancer, including lung cancer. Herein, we investigated the
      effects of pterostilbene, an analog of resveratrol found in blueberries, on lung
      cancer, in vitro. We hypothesized that pterostilbene would inhibit lung cancer
      cell growth in vitro by a pro-apoptotic mechanism. METHODS: Two lung cancer cell
      lines (NCI-H460 and SK-MES-1) were cultured using standard techniques. Cells were
      treated with increasing doses of pterostilbene (10-100 microM). Cell viability
      was measured at 24, 48, and 72h using a MTT assay. Apo-ONE Caspase-3/7 assay was
      used to evaluate caspase activity. T-test and two-way ANOVA were used for
      statistical analysis. RESULTS: Pterostilbene significantly decreased cell
      viability in lung cancer cells in a concentration- and time-dependent manner
      (P<0.001). Concentrations greater than 20 microM of pterostilbene produced
      significant growth inhibition by 72h (P<0.001). Apoptosis and caspase-3/7
      activity were significantly increased by pterostilbene treatment (P<0.05).
      CONCLUSIONS: Pterostilbene inhibits growth via apoptosis induction in vitro.
      Further in vitro mechanistic studies and in vivo experiments are warranted to
      determine the potential role for pterostilbene in lung cancer treatment or
      prevention.

PMID- 20031167
TI  - Significance of insulin signaling in liver regeneration triggered by portal vein
      ligation.
AB  - BACKGROUND: To investigate the role of insulin signaling in liver regeneration
      following portal vein ligation (PVL). MATERIALS AND METHODS: Streptozotocin
      induced insulin-deficient rats underwent PVL, and were sacrificed at indicated
      time points. Liver regeneration indices, including volumetric shifting, BrdU,
      proliferative cell nuclear antigen (PCNA), and Ki-67 labeling index, were
      determined. Cell cycle markers, telomerase reverse transcriptase (TERT), and
      apoptosis-related genes were detected using quantitative real time polymerase
      chain reaction (PCR). Cell cycle analysis was determined using flow cytometry.
      Expression of insulin-like growth factor receptor (IGFR)-2 and TGFbeta1 were
      determined using Western blot. RESULTS: Restituted liver mass and redistributed
      volume ratio of insulin-deficient rats were decreased compared with those of
      normal rats. Labeling index of BrdU and PCNA of insulin-deficient rats were
      increased compared with normal rats, evidenced by an increased S-phase fraction
      detected by flow cytometry. Expression of cyclin A2, cyclin B1, TERT mRNA, and
      telomerase activity were decreased in insulin-deficient rats. Increased Bax,
      Daxx, and JNK mRNA expression and decreased Bcl X(L) expression in insulin
      deficient rats, led to increased hepatocyte apoptosis than normal rats. Finally,
      expression of IGFR-2 was increased in insulin-deficient rats. CONCLUSIONS:
      Insulin signaling plays an important role in liver regeneration triggered by
      portal vein ligation.

PMID- 20031168
TI  - Laparoscopic versus open appendectomy in children: outcomes comparison based on a
      statewide analysis.
AB  - BACKGROUND: To compare the differences in hospital utilization and complications
      between laparoscopic (LA) and open appendectomy (OA) for pediatric appendicitis.
      METHODS: A retrospective study from 1999 to 2006 of children aged 1 to 18 y with
      appendicitis, from the California Patient Discharge Database was performed.
      Children with significant comorbidities were excluded. Initial hospital course,
      subsequent readmissions, and the need for additional procedures were analyzed.
      RESULTS: The use of LA increased steadily from 19% in 1999 to 52% in 2006.
      Overall, 95,806 children were studied. Readmissions were tracked over a median
      period of 3 y. LA was associated with increased need for postoperative intra
      abdominal abscess drainage for both perforated appendicitis (4.9% versus 3.8%,
      P<0.001) and nonperforated appendicitis (0.6% versus 0.3%, P<0.001) compared with
      OA. Multivariate regression showed an increased risk of postoperative abscess
      drainage for children after LA compared with OA (RR 1.81, 99% CI 1.41-2.27).
      However, the lengths of readmission hospitalizations were the same between the
      two groups (5.8 versus 5.7 d, P=NS). CONCLUSION: LA has become the preferred
      operation for pediatric appendicitis. The need for postoperative abscess drainage
      is small, and laparoscopy appears to increase this risk slightly. However, LA did
      not affect long-term hospital utilizations.

PMID- 20031169
TI  - Effect of pravastatin on experimental diabetic wound healing.
AB  - BACKGROUND: Impaired wound healing in diabetes has been associated with
      abnormalities in wound nitric oxide (NO) and nitric oxide synthase (NOS)
      availability. Efforts to alter the profile of NO expression in the wound
      microenvironment have proven to be successful in partially restoring wound
      healing deficits. We investigated the effects of pravastatin, a HMG Co A
      reductase inhibitor on endothelial nitric oxide synthase (eNOS) expression, NO
      production, and wound healing in a diabetic acute wound healing model. MATERIALS
      AND METHODS: Of 70 male Sprague Dawley rats injected with streptozocin, 62 were
      confirmed diabetic after 1 wk. Animals were randomized into two groups: (1)
      diabetic control and (2) diabetic treated with pravastatin. Pravastatin sodium
      was gavaged at 0.4 mg/kg/d for 5 d, after which all animals underwent dorsal
      incision with insertion of subcutaneous sponges. Breaking strengths and
      hydroxyproline were measured on days 1, 3, and 10 post-wounding. Wound fluid was
      analyzed for nitrate/nitrite production. Tissue samples were analyzed for eNOS
      expression. RESULTS: We demonstrated enhanced wound breaking strengths,
      hydroxyproline accumulation, an up-regulation in eNOS expression, and elevated NO
      levels in the pravastatin treated group. CONCLUSION: We have shown that
      pravastatin, in an experimental model of diabetes may through up-regulation of
      eNOS and NO expression improve wound healing.

PMID- 20031170
TI  - The porcine hepatic arterial supply, its variations and their influence on the
      extracorporeal perfusion of the liver.
AB  - BACKGROUND: Variations in the porcine hepatic vasculature may contribute to the
      outcome of experiments based on liver perfusion models. We studied the hepatic
      artery (HA), variations of its branches, and the correlation with the resultant
      perfusion. MATERIALS AND METHODS: Nineteen animals were used. After 6 h of
      perfusion, dissection of the HA and its branches was conducted up to the
      insertion in the liver parenchyma. Data about the macroscopic appearance of lobes
      and the pattern of branching were recorded. RESULTS: In all cases, the HA
      bifurcated into two constant branches, one for the LL/LM lobes (further divided
      in two vessels for each lobe) and one for the RM lobe. Five main patterns were
      identified involving vessels for the RL and the CL lobes. Two variations produced
      complete and uniform perfusion of the entire liver in all cases, while in the
      remaining cases, only part of them were completely perfused. CONCLUSIONS: Some
      variants of the porcine HA and its branches are associated with the risk of
      incomplete perfusion if the perfusion cannula placement does not take the
      individual hepatic arterial anatomy into account. Understanding of the hepatic
      arteries branching patterns is essential when ex vivo perfusion models are being
      established.

PMID- 20031171
TI  - Evaluation of fundamental critical care course in Kenya: knowledge, attitude, and
      practice.
AB  - BACKGROUND: Critical care training for medical personnel is crucial for the
      survival of the highest acuity patients. The Fundamental Critical Care Course
      (FCCS), a critical care course developed by the Society of Critical Care
      Medicine, permits course adaption and, thus, has potential for global
      dissemination. The FCCS course was provided in two Kenyan hospitals after minimal
      adaption. Participant knowledge and confidence gain as well as FCCS applicability
      to an African context were evaluated. METHODS: Questionnaires and a multiple
      choice test were administered to assess knowledge, attitude, and self-reported
      confidence or self-efficacy. For applicability, the pre-course questionnaire
      assessed participant expectations and existing levels of confidence/knowledge in
      the care of the critically ill patient. Post-course, the participant evaluated
      the overall quality of the course, lectures, and skill stations along with
      context applicability questions. RESULTS: There were 100 participants, 45
      doctors, 45 nurses, and 10 clinical officers. There was a 22.7% gain in the mean
      test score (P < 0.0001) after the course, with 98% of participants showing
      improvement. Confidence to perform new skills post-course, or self-efficacy, was
      demonstrated by a median of 4 or greater on a Likert scale of 5 (most confident)
      in 10 of 12 clinical scenarios and in 11 of 14 new procedures. There was a
      consistency between areas reported as needed expertise, and participant
      evaluation of similar lecture and skill station's quality and appropriateness.
      The most common areas reported were mechanical ventilation, patient monitoring,
      and their related procedures. CONCLUSIONS: The FCCS course met participant's
      expectations and was reported as applicable for the Kenyan context with minimal
      adaption. Post-course, knowledge improved and confidence increased for
      implementation of new skills in clinical care situations. We confirmed the
      effectiveness and relevancy of the FCCS course for other resource-constrained
      health care settings.

PMID- 20031173
TI  - Nile red staining helps select cells with adrenocortical progenitor cell-like
      phenotype.

PMID- 20031172
TI  - Pterostilbene inhibits breast cancer in vitro through mitochondrial
      depolarization and induction of caspase-dependent apoptosis.
AB  - BACKGROUND: Epidemiologic studies suggest that diets high in fruits and
      vegetables reduce cancer risk. Resveratrol, a compound present in grapes, has
      been shown to inhibit a variety of primary tumors. Pterostilbene, an analogue of
      resveratrol found in blueberries, has both antioxidant and antiproliferative
      properties. We hypothesized that pterostilbene would induce apoptosis and inhibit
      breast cancer cell growth in vitro. METHODS: Breast cancer cells were treated
      with graduated doses of pterostilbene. Cell viability was measured by MTT assay.
      Apoptosis was evaluated via DNA fragmentation assay and TUNEL assay. Apo-ONE
      caspase-3/7 assay was used to evaluate caspase activity. Flow cytometry was used
      to evaluate mitochondrial depolarization, superoxide formation, and cell cycle.
      Student's t-test and two-way ANOVA with Bonferroni posttests were utilized for
      statistical analysis. RESULTS: Pterostilbene decreased breast cancer cell
      viability in a concentration- and time-dependent manner. Pterostilbene treatment
      increased caspase-3/7 activity and apoptosis in both cell lines. Caspase-3/7
      inhibitors completely reversed pterostilbene's effects on cell viability.
      Pterostilbene treatment triggered mitochondrial depolarization, increased
      superoxide anion, and caused alteration in cell cycle. CONCLUSIONS: Pterostilbene
      treatment inhibits the growth of breast cancer in vitro through caspase-dependent
      apoptosis. Mitochondrial membrane depolarization and increased superoxide anion
      may contribute to the activation downstream effector caspases. Caspase inhibition
      leads to complete reversal of pterostilbene's effect on cell viability. Further
      in vitro mechanistic studies and in vivo experiments are warranted to determine
      its potential for the treatment of breast cancer.

PMID- 20031174
TI  - Liver regeneration is impaired in macrophage colony stimulating factor deficient
      mice after partial hepatectomy: the role of M-CSF-induced macrophages.
AB  - Macrophage colony stimulating factor (M-CSF), which induces maturation of
      macrophages, is notably expressed in the liver. Thus, the specific purpose of
      this study was to investigate the role of M-CSF in liver regeneration after
      partial hepatectomy (PH). Osteopetrotic (op/op) mice, genetically lacking
      functional M-CSF, or their littermate mice underwent 70% PH. Animals were
      sacrificed at the designated time points after PH, and remnant liver tissues were
      harvested for further investigations. Proliferation of hepatocytes was evaluated
      by the expression of BrdU and the liver-body weight ratio. The mRNA expression
      levels of TNF-alpha and IL-6 and protein expression levels of phosphorylated (p)
      STAT3 were measured. The number of Kupffer cells (KCs) was determined by
      immunohistochemistry. Furthermore, KCs were isolated from op/op mice or
      littermate mice, and mRNA expression levels of TNF- alpha and IL-6 were assessed
      after stimulation with LPS. In littermate mice, steady liver regeneration was
      observed. The number of KCs reduced markedly by about 60% in the op/op mice
      compared with littermates as reported previously. Furthermore, these cells were
      morphologically small and immature. In littermate mice, the peak expression
      levels of TNF-alpha and IL-6 in the liver was observed 1h after PH, which was
      consistent with data in previous reports. In contrast, in op/op mice, the peak
      expression levels were observed 3 h after PH and were significantly lower
      compared with littermate mice. As a result, the proliferation of hepatocytes was
      significantly impaired in op/op mice. The mRNA expression level of IL-6, but not
      TNF-alpha,was significantly reduced in isolated KCs from op/op mice compared with
      the littermates after stimulation with LPS, suggesting that the function of KCs
      is different between op/op mice and littermate mice. To clarify the role of M-CSF
      in liver regeneration, op/op mice received intraperitoneally, mouse recombinant M
      CSF 2 d before PH, and liver regeneration was also assessed. As a result, the
      numbers of Kupffer cells and liver regeneration were recovered in the op/op mice
      treated with M-CSF to a similar extent to those in their littermates. Thus, M-CSF
      induced hepatic macrophages play an important role in liver regeneration after
      PH.

PMID- 20031175
TI  - Occurrence of anthropogenic and naturally-produced organohalogenated compounds in
      tissues of Black Sea harbour porpoises.
AB  - Harbour porpoises are one of the three cetacean species inhabiting the Black Sea.
      This is the first study to report on polybrominated diphenyl ethers (PBDEs) and
      naturally-produced compounds, methoxylated PBDEs (MeO-PBDEs) and polybrominated
      hexahydroxanthene derivatives (PBHDs), in tissues (kidney, brain, blubber, liver,
      muscle) of male harbour porpoises (11 adults, 9 juveniles) from the Black Sea.
      Lipid-normalized concentrations decreased from muscle>blubber>liver>kidney>brain
      for the sum of polychlorinated biphenyls (PCBs) and for the sum of PBDEs. Among
      the naturally-produced compounds, levels of PBHDs were higher than of MeO-PBDEs,
      with tri-BHD and 6-MeO-BDE 47 being the dominant compounds for both groups,
      respectively. Concentrations of naturally-produced compounds decreased from
      blubber to brain, similarly to the sum of DDT and metabolites (DDXs).
      Concentrations of DDXs were highest, followed by PCBs, HCB, PBHDs, PBDEs and MeO
      PBDEs. Levels of PCBs and PBDEs in blubber were lower than concentrations
      reported for harbour porpoises from the North Sea, while concentrations of DDXs
      were higher.

PMID- 20031176
TI  - Marine species mortality in derelict fishing nets in Puget Sound, WA and the
      cost/benefits of derelict net removal.
AB  - Derelict fishing gear persists for decades and impacts marine species and
      underwater habitats. Agencies and organizations are removing significant amounts
      of derelict gear from marine waters in the United States. Using data collected
      from repeated survey dives on derelict gillnets in Puget Sound, Washington, we
      estimated the daily catch rate of a given derelict gillnet, and developed a model
      to predict expected total mortality caused by a given net based on entanglement
      data collected upon its removal. We also generated a cost:benefit ratio for
      derelict gear removal utilizing known true costs compared to known market values
      of the resources benefiting from derelict gear removal. For one study net, we
      calculated 4368 crab entangled during the impact lifetime of the net, at a loss
      of 19,656 dollars of Dungeness crab to the commercial fishery, compared to 1358
      dollars in costs to remove a given gillnet, yielding a cost:benefit ratio of
      1:14.5.

PMID- 20031177
TI  - Interactive effects of metal contamination and pathogenic organisms on the marine
      bivalve Cerastoderma edule.
AB  - The present study evaluated the interactive effects of cadmium contamination and
      pathogenic organisms (trematodes Himasthla elongata and bacteria Vibrio tapetis)
      singularly and in combination during 7 days on the bivalve Cerastoderma edule.
      Some defense-related activities were analyzed such as genetic expression,
      metallothionein and immune responses. Trematode metacercarial infection, similar
      whatever the treatment, induced the strongest responses of immune parameters.
      Particularly, the interaction between cadmium and parasite exposures induced
      unusual responses on gene expression and immune responses. No effect of bacterial
      challenge appeared on bivalve responses, nevertheless a strong mortality of V.
      tapetis infected cockles occurred between 7 and 14 days. Cadmium bioaccumulation
      was significantly modulated by both pathogenic organisms. Furthermore, an
      antagonistic effect of trematodes and bacteria was shown on metal bioaccumulation
      of co-infected cockles. These results highlighted the importance of considering
      the multiplicity of perturbation sources in coastal ecosystems to assess the
      health status of organisms.

PMID- 20031178
TI  - Acylated flavonol tetraglycosides from Delphinium gracile.
AB  - An ethanol extract of the aerial parts of Delphinium gracile DC. yielded five
      flavonol glycosides quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(E-p
      caffeoyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta-d
      glucopyranoside (1), quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(E-p
      coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta
      d-glucopyranoside (2), quercetin-3-O-{[beta-d-xylopyranosyl (1-->3)-4-O-(Z-p
      coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranosyl (1-->2)]}-beta
      d-glucopyranoside (3), kaempferol-3-O-{[beta-d-glucopyranosyl (1-->3)-4-O-(E-p
      coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranoside-7-O-(4-O
      acetyl)-alpha-l-rhamnopyranoside (4) kaempferol-3-O-{[beta-d-glucopyranosyl (1-
      >3)-4-O-(E-p-coumaroyl)-alpha-l-rhamnopyranosyl (1-->6)][beta-d-glucopyranoside-7
      O-(4-O-acetyl)-alpha-l-rhamnopyranoside (5) in addition to 4-(beta-d
      glucopyranosyloxy)-6-methyl-2H-pyran-2-one (6) and rutin. Structures were
      elucidated by spectroscopic methods.

PMID- 20031179
TI  - Co-existence of classical scrapie and Nor98 in a sheep from an Italian outbreak.
AB  - Nor98 is an atypical scrapie strain characterized by a molecular pattern and
      brain distribution of the pathological prion protein (PrP(Sc)) different from
      classical scrapie. In Italy, 69 atypical cases have been identified so far and
      all were characterized as Nor98 strain. In this paper we report an unusual case
      in a sheep which showed immunohistochemical and molecular features of PrP(Sc)
      different from the other atypical cases. The sheep was from an outbreak where the
      index and the other four cases were affected by classical scrapie.
      Histopathological, immunohistochemical and Western blot analyses on the brain of
      the unusual case revealed the simultaneous presence of pathological features
      characteristic of Nor98 and classical scrapie. Interestingly, the prevalent
      disease phenotype in the brainstem was classical scrapie-like, while in the
      cerebral cortex and cerebellum the Nor98 phenotype was dominant. The sub
      mandibular lymph node was positive and showed a PrP(Sc) molecular pattern
      referable to classical scrapie. The PrP genotype was AL(141)RQ/AF(141)RQ. Taken
      together, the occurrence of classical scrapie in the outbreak, the PrP genotype,
      the involvement of different cellular targets in the brain and the pathological
      and molecular PrP(Sc) features observed suggest that this unusual case may result
      from the co-existence of Nor98 and classical scrapie.

PMID- 20031180
TI  - First report of porcine circovirus type 2 infections in Cuba.
AB  - To obtain information about the porcine circovirus type 2 (PCV2) infection status
      of pigs in Cuba and the probable association of PCV2 with other porcine viruses,
      tissue samples collected from ill pigs were evaluated using polymerase chain
      reaction (PCR). The PCR analysis showed that 67.7% of the samples (23/34) from
      seven swine herds of six different geographic regions were detected to be
      positive for PCV2. Ten of the 23 PCV2 positive samples (43.5%) shown a concurrent
      infection with porcine parvovirus (PPV) and 17 of 23 PCV2 positive samples
      (73.9%) exhibited a concomitant infection with classical swine fever virus
      (CSFV). This study is the first report of PCV2 infecting pigs with different
      clinical conditions in Cuban swine herds and provides evidence of PCV2 co
      infection with PPV and CSFV in the field.

PMID- 20031182
TI  - Efficient temperature compensation strategies for guided wave structural health
      monitoring.
AB  - The application of temperature compensation strategies is important when using a
      guided wave structural health monitoring system. It has been shown by different
      authors that the influence of changing environmental and operational conditions,
      especially temperature, limits performance. This paper quantitatively describes
      two different methods to compensate for the temperature effect, namely optimal
      baseline selection (OBS) and baseline signal stretch (BSS). The effect of
      temperature separation between baseline time-traces in OBS and the parameters
      used in the BSS method are investigated. A combined strategy that uses both OBS
      and BSS is considered. Theoretical results are compared, using data from two
      independent long-term experiments, which use predominantly A(0) mode and S(0)
      mode data respectively. These confirm that the performance of OBS and BSS
      quantitatively agrees with predictions and also demonstrate that the combination
      of OBS and BSS is a robust practical solution to temperature compensation.

PMID- 20031181
TI  - Study on precipitation of struvite and struvite-K crystal in goats during onset
      of urolithiasis.
AB  - To learn more about the biomineralization process of struvite in ruminants, a
      seldom noticeable crystal, struvite-K, was investigated in six goats in which
      urolithiasis was induced by feeding a cottonseed meal and rice straw diet
      supplemented with MgO. The compositions of crystals and calculi were studied by
      chemical qualitative analysis and X-ray energy dispersive spectrometry (EDS). The
      activity product (AP) and relative supersaturation (RSS) of magnesium ammonium
      phosphate (MAP) and potassium magnesium phosphate (MKP) were calculated to
      compare the difference of crystals formed in this process. The results showed
      that calculi consisted of MAP with a little MKP. Crystals in the urine consisted
      of MAP and MKP before stone formation, but crystals in urine after stone
      formation mainly consisted of MKP. The AP and RSS of MAP and MKP significantly
      decreased after stone formation. It was concluded that MAP and MKP may coexist in
      the crystals of urine before struvite calculi formation but MKP did not
      precipitate to struvite calculi and was separated out as crystal sedimentation of
      urine. The changes of crystallization of MAP and MKP contributed partially to the
      supersaturation status of MAP and MKP during struvite stone formation.

PMID- 20031183
TI  - Ultrasonic transcutaneous energy transfer for powering implanted devices.
AB  - This paper investigates ultrasonic transcutaneous energy transfer (UTET) as a
      method for energizing implanted devices at power level up to a few 100 mW. We
      propose a continuous wave 673 kHz single frequency operation to power devices
      implanted up to 40 mm deep subcutaneously. The proposed UTET demonstrated an
      overall peak power transfer efficiency of 27% at 70 mW output power (rectified DC
      power at the load). The transducers consisted of PZT plane discs of 15 mm
      diameter and 1.3mm thick acoustic matching layer made of graphite. The power
      rectifier on the implant side attained 88.5% power transfer efficiency. The
      proposed approach is analyzed in detail, with design considerations provided to
      address issues such as recommended operating frequency range, acoustic link
      matching, receiver's rectifying electronics, and tissue bio-safety concerns.
      Global optimization and design considerations for maximum power transfer are
      presented and verified by means of finite element simulations and experimental
      results.

PMID- 20031184
TI  - Water purification from metal ions using carbon nanoparticle-conjugated polymer
      nanocomposites.
AB  - The paper deals with a novel method of obtaining nanocarbon-conjugated polymer
      nanocomposites (NCPC) using nanocarbon colloids (NCC) and polyethylenimine (PEI)
      for water purification from metal ions. Size of NCC, process of NCPC synthesis,
      its chemical characteristics, ratio of NCC and PEI in NCPC, speed of coagulation
      of NCPC, mechanism of interaction of metal ions with NCPC, ability of removing
      metal ions from water by NCPC against pH have been studied. NCPC has a bonding
      capacity of 4.0-5.7mmol/g at pH 6 for most of the divalent metal ions. Percent of
      sorption of Zn(2+), Cd(2+), Cu(2+), Hg(2+), Ni(2+), Cr(6+) ions is higher than
      99%. Lifetime of NCPC before coagulation in the treated water is 1s-1000min and
      depends on the ratio of polymeric molecules and carbon nanoparticle
      concentrations. Results of laboratory tests of the method are described.

PMID- 20031185
TI  - Hypochlorite oxidation of select androgenic steroids.
AB  - Steroid hormones are vital for regulation of various biological functions
      including sexual development. Elevated concentrations of natural and synthetic
      androgenic steroids have been shown to adversely affect normal development in
      indigenous aqueous species. Androgens and their synthetic analogs released from
      agricultural activities and wastewater discharge may be introduced into drinking
      water sources. The fate of androgenic steroids during drinking water treatment,
      specifically the use of chlorine for biological control, has not been extensively
      studied. As such, this study focuses on the hypochlorite oxidation of a select
      number of androgenic compounds that vary in their structural composition. Where a
      favorable reaction is observed, we also attempt to describe the product
      distribution. The results show compounds that possess a ketonic functional group
      conjugated with a double bond inhibit oxidation by hypochlorite in the absence of
      biological or indirect oxidative pathways. Oxidative reactivity in the presence
      of hypochlorite was favorably correlated with the presence of isolated
      unsaturated carbon bonds and resulted in various transformation products.

PMID- 20031186
TI  - Nitrate removal by a paired electrolysis on copper and Ti/IrO(2) coupled
      electrodes - influence of the anode/cathode surface area ratio.
AB  - In this study, nitrate removal in alkaline media by a paired electrolysis with
      copper cathode and Ti/IrO(2) anode enabled the conversion of nitrate to nitrogen.
      Optimum conditions for carrying out reduction of nitrate to ammonia and
      subsequent oxidation of the produced ammonia to nitrogen were found. At the
      copper cathode, electroreduction of nitrate to ammonia was optimal near -1.4 V vs
      Hg/HgO. At the Ti/IrO(2) anode, a pH value of 12, the presence of chloride and a
      potential fixed around 2.3 V vs Hg/HgO permitted the production of hypochlorite,
      leading to the oxidation of ammonia to nitrogen with a N(2) selectivity of 100%.
      Controlling the cathode/anode surface area ratio, and thus the current density,
      appeared to be a very efficient way of shifting electrode potentials to optimal
      values, consequently favoring the conversion of nitrate to nitrogen during a
      paired galvanostatic electrolysis. A cathode/anode surface area ratio of 2.25 was
      shown to be the most efficient to convert nitrate to nitrogen.

PMID- 20031187
TI  - In situ relationships between spatio-temporal variations in diuron concentrations
      and phototrophic biofilm tolerance in a contaminated river.
AB  - Microbial biofilms are useful indicators for monitoring the ecological state of
      rivers. When assessing the effects of toxicants on microbial communities in
      natural ecosystems, special attention must be paid to the distinction between
      such effects and those resulting from other environmental variables. The
      pollution-induced community tolerance (PICT) approach offers the means to
      partially isolate effects of individual toxicants within a complex ecosystem by
      studying shifts in community sensitivity. To validate PICT for site-specific risk
      assessment, we investigated how closely diuron tolerance acquisition by
      photoautrophic biofilm communities could reflect their previous in situ exposure
      to this herbicide. To this end, a field survey was conducted for 9 months in a
      French river contaminated by diuron inputs from adjacent vineyards. Spatio
      temporal variations in diuron tolerance capacities of photoautotrophic
      communities were estimated monthly using short-term photosynthetic bioassays. The
      biological survey was coupled with intensive physico-chemical monitoring to
      analyze the environmental factors influencing tolerance induction. We revealed a
      possible influence of three co-varying environmental variables (nitrates,
      conductivity and temperature), but statistical analysis clearly demonstrated that
      the main factor explaining variation in diuron sensitivity was the mean in situ
      diuron exposure level during biofilm colonization periods. A remarkable
      exponential correlation between EC(50) values and in situ diuron concentrations
      (R(2)=0.90, p<0.0001) was recorded, confirming that PICT can be a powerful tool
      for the environmental monitoring of rivers.

PMID- 20031188
TI  - Chemical cleaning of potable water membranes: The cost benefit of optimisation.
AB  - A study of the variability in chemical cleaning factors on permeability recovery
      for potable water microfiltration (MF) and ultrafiltration (UF) systems has been
      carried out employing a cost model simulating plant fouling and cleaning regimes.
      The impact of a range of operating and cleaning factors on operating cost
      variation was computed using algorithms describing operational and cleaning
      factor relationships with permeability recovery data measured from bench scale
      tests on fibres sampled from full-scale operational plants. The model proceeded
      through sequencing of the cleaning and backwashing operations to generate
      transmembrane pressure (TMP), and so head loss, transients. A number of cleaning
      scenarios were considered for each plant, based on employing either a threshold
      TMP or fixed chemical cleaning intervals. The resulting TMP profiles were then
      converted to operational costs. The effect of the variability in permeability
      recovery on annual operating costs was calculated for each of the simulations. It
      was evident that significant operating cost reductions were possible from
      optimisation of the cleaning protocol. Cost benefit varied according to facets of
      plant design and operation; the innate variability in permeability recovery
      precluded the correlation of cleaning efficacy with fouling characteristics.

PMID- 20031189
TI  - Drugs degrading photocatalytically: Kinetics and mechanisms of ofloxacin and
      atenolol removal on titania suspensions.
AB  - The conversion of the antibiotic ofloxacin and the beta-blocker atenolol by means
      of TiO(2) photocatalysis was investigated. Irradiation was provided by a UVA lamp
      at 3.37x10(-6)einstein/s photon flux, while emphasis was given on the effect of
      catalyst type and loading (50-1500mg/L), initial substrate concentration (5
      20mg/L), initial pH (3-10) and the effect of H(2)O(2) (0.07-1.4mM) as an
      additional oxidant on substrate conversion and mineralization in various matrices
      (i.e. pure water, groundwater and treated municipal effluent). Conversion was
      assessed measuring sample absorbance at 288 and 224nm for ofloxacin and atenolol,
      respectively, while mineralization measuring the dissolved organic carbon.
      Degussa P25 TiO(2) was found to be more active than other TiO(2) samples for
      either substrate degradation, with ofloxacin being more reactive than atenolol.
      Conversion generally increased with increasing catalyst loading, decreasing
      initial substrate concentration and adding H(2)O(2), while the effect of solution
      pH was substrate-specific. Reaction rates, following a Langmuir-Hinshelwood
      kinetic expression, were maximized at a catalyst to substrate concentration ratio
      (w/w) of 50 and 15 for ofloxacin and atenolol, respectively, while higher ratios
      led to reduced efficiency. Likewise, high concentrations of H(2)O(2) had an
      adverse effect on reaction, presumably due to excessive oxidant scavenging
      radicals and other reactive species. The ecotoxicity of ofloxacin and atenolol to
      freshwater species Daphnia magna was found to increase with increasing substrate
      concentration (1-10mg/L) and exposure time (24-48h), with atenolol being more
      toxic than ofloxacin. Photocatalytic treatment eliminated nearly completely
      toxicity and this was more pronounced for atenolol.

PMID- 20031190
TI  - Fate of aerobic bacterial granules with fungal contamination under different
      organic loading conditions.
AB  - Aerobic sludge granulation is an attractive new technology for biological
      wastewater treatment. However, the instability of aerobic granules caused by
      fungal growth is still one of the main problems encountered in granular
      bioreactors. In this study, laboratory experiments were conducted to investigate
      the fate and transformation of aerobic granules under different organic loading
      conditions. Bacterial granules (2-3mm) in a poor condition with fungi-like black
      filamentous growth were seeded into two 1L batch reactors. After more than 100d
      of cultivation, the small seed granules in the two reactors had grown into two
      different types of large granules (>20mm) with different and unique morphological
      features. In reactor R1 with a high organic loading rate of 2.0g COD L(-1)d(-1),
      the black filaments mostly disappeared from the granules, and the dominance of
      rod-shaped bacteria was recovered. In contrast, at a low loading of 0.5g COD L(
      1)d(-1) in reactor R2, the filaments eventually became dominant in the black
      fungal granules. The bacteria in R1 granules had a unique web-like structure with
      large pores of a few hundred microm in size, which would allow for effective
      substrate and oxygen transport into the interior of the granules. DNA-based
      molecular analysis indicated the evolution of the bacterial population in R1 and
      that of the eukaryal community in R2. The experimental results suggest that a
      high loading rate can be an effective means of helping to control fungal bloom,
      recover bacterial domination and restore the stability of aerobic granules that
      suffer from fungal contamination.

PMID- 20031191
TI  - Were snares and traps used in the Middle Stone Age and does it matter? A review
      and a case study from Sibudu, South Africa.
AB  - The concept of remote capture involved in the creation and use of snares and
      traps is one of several indicators that can be used for the recognition of
      enhanced working memory and complex cognition. It can be argued that this humble
      technology is a more reliable indicator of complex cognition than encounter
      hunting, for example with spears. It is difficult to recognize snares and traps
      archaeologically because they are generally made from materials that do not
      preserve well. To infer their presence in the past, it is therefore necessary to
      rely on circumstantial evidence such as mortality profiles, taxonomic diversity
      and high frequencies of creatures that are susceptible to capture in snares or
      traps. Clearly there are some problems with using snares to infer complex
      cognition because people do not necessarily choose meat-getting strategies with
      the lowest costs. Although snares make economic sense because they reduce search
      costs, their use by modern hunters is not associated with the type of status
      accorded to other means of hunting. Social demands, more than economic or
      environmental ones, may consequently have determined the amount of snaring and
      trapping that occurred in the past. Because of social attitudes, an absence of
      snaring need not mean that people were incapable of using this technique. At
      Sibudu, a South African Middle Stone Age site, snares or other non-selective
      capture techniques may have been used during the Howiesons Poort and perhaps also
      the Still Bay Industry. The circumstantial evidence consists of 1. high frequency
      representations of animals that prefer forested environments, including the tiny
      blue duiker (adult and juvenile) and the dangerous bushpig, 2. high frequencies
      of small mammals, 3. high taxonomic diversity and, 4. the presence of small
      carnivores. Importantly, the Howiesons Poort faunal assemblage is different from
      that in more recent Middle Stone Age occupations of the site.

PMID- 20031192
TI  - Involvement of Heparanase in early pregnancy losses.
AB  - BACKGROUND: Heparanase cloned from and abundant in the placenta is implicated in
      cell invasion, tumor angiogenesis and metastasis. Recently, we demonstrated that
      heparanase is involved in the regulation of the hemostatic system. Heparanase was
      found to up-regulate tissue factor (TF) expression (Nadir et al., JTH, 2006) and
      interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading
      to dissociation of TFPI from the cell membrane resulting in increased cell
      surface coagulation activity (Nadir et al., TH, 2008). Herein, we investigated
      the role of heparanase in the placenta, focusing on its effect on TF, TFPI, TFPI
      2, and vascular endothelial growth factor (VEGF)-A. METHODS: Twenty formalin
      embedded placenta samples of abortions (weeks 6-10) were studied applying real
      time RT-PCR and immunostaining. Ten cases were miscarriages of women with
      thrombophilia and recurrent fetal losses, and ten control cases were pregnancy
      terminations. JAR (human choriocarcinoma trophoblasts) cells were transfected
      with full-length heparanase cDNA or incubated with active (50+8 kDa) recombinant
      heparanase and the effects on TF, TFPI, TFPI-2 and VEGF-A were examined using
      real time RT-PCR and immunoblotting. RESULTS: Sections obtained from miscarriages
      revealed increased (2-3-folds) levels of heparanase, VEGF-A and TFPI-2 compared
      to placentas from controls in maternal as well as in fetal placenta elements. JAR
      cells overexpressing heparanase or incubated with exogenous recombinant
      heparanase exhibited a 2-3-fold increase in TFPI and TFPI-2 in cell lysates both
      at the protein and mRNA levels, with no detectable effect on VEGF-A and TF
      levels. Accumulation of TFPI and TFPI-2 in the cell culture medium was increased
      4-6-folds, exceeding the observed induction of TFPI and TFPI-2 gene
      transcription. CONCLUSIONS: These results indicate a regulatory effect of
      heparanase on TFPI and TFPI-2 in trophoblasts, suggesting a potential involvement
      of heparanase in early miscarriages.

PMID- 20031193
TI  - Spermidine/spermine N1-acetyltranferase modulation by novel folate cycle
      inhibitors in cisplatin-sensitive and -resistant human ovarian cancer cell lines.
AB  - OBJECTIVE: Polyamines have been shown to play a role in the growth and survival
      of several solid tumors, including ovarian cancer. Intracellular polyamine
      depletion by the inhibition of biosynthesis enzymes or by the induction of the
      catabolic pathway leads to antiproliferative effects in many different tumor cell
      lines. Recent studies showed that the thymidylate synthase inhibitor 5
      fluorouracil (5-FU) affects polyamine metabolism in colon carcinoma cells through
      the induction of the key catabolic enzyme spermidine/spermine N1
      acetyltransferase (SSAT). METHODS: We therefore examined whether combinations of
      novel folate cycle inhibitors with quinoxaline structure and drugs that
      specifically target polyamine metabolism, such as diethylderivatives of
      norspermine (DENSPM) or spermine (BESpm), have synergistic effect in killing
      cisplatin-sensitive and drug-resistant daughter human ovarian cell lines.
      RESULTS: Our results showed that simultaneous drug combination or quinoxaline pre
      treatment synergistically increased SSAT expression, depleted polyamines,
      increased reactive oxygen species production, and produced synergistic tumor cell
      killing in both cell lines. Of note, this combined therapy increased the
      chemosensitivity of cisplatin-resistant cells and cross-resistant to the
      polyamine analogues. On the contrary, some pre-treatment regimens of Spm
      analogues were antagonistic. CONCLUSIONS: These results show that SSAT plays an
      important role in novel folate cycle inhibitors effects and suggest that their
      combination with analogues has potential for development as therapy for ovarian
      carcinoma based on SSAT modulation.

PMID- 20031194
TI  - Color-coded real-time cellular imaging of lung T-lymphocyte accumulation and
      focus formation in a mouse asthma model.
AB  - BACKGROUND: A critical role for CD4(+)T(H)2 cells in the pathogenesis of acute
      asthma has been demonstrated in the studies of human asthma as well as of animal
      models of asthma. T(H)2-cell migration into the lung is crucial for the
      initiation of asthma phenotype, but the dynamics of this process are poorly
      understood because it has been difficult to visualize this process. OBJECTIVE:
      Our aim was to image the cellular dynamics of the migration of T(H)2 cells into
      the lung of living animals in a mouse model of asthma and identify the cellular
      processes required for the initiation of the asthma phenotype. METHODS: We
      developed a color-coded real-time imaging model of cell migration into the lung
      using green fluorescent protein (GFP) and red fluorescent protein (RFP)
      transgenic CD4 T cells. RESULTS: Selective accumulation of antigen-specific CD4 T
      cells in the lungs was quantitatively imaged in a mouse model of asthma. The
      inhibition of accumulation by dexamethasone was imaged. Accumulating GFP(+) T(H)2
      cells formed foci in the lungs from 6 to 20 hours after antigen inhalation. This
      process was also inhibited by the administration of anti-intercellular adhesion
      molecule 1 or anti-vascular cell adhesion molecule 1 mAbs. Two days after
      inhalation of antigen, GFP(+) T(H)2 cells were detected in the area of eosinophil
      infiltration. CONCLUSION: Focus formation generated by accumulating antigen
      specific T(H)2 cells in the lung appeared to be a critical process in the
      initiation of the asthma phenotype. This new model enables the study of in vivo
      cell biology of airway inflammation and novel drug discovery for lung
      inflammatory diseases.

PMID- 20031195
TI  - The effect of estradiol on COX-2, EP2, and EP4 mRNA expression and the
      extracellular matrix in the cervix of the hypogonadotrophic, ovariectomized ewe.
AB  - There is a degree of cervical relaxation in the ewe at estrus that is regulated
      by changes in prostaglandin synthesis, prostaglandin receptor expression, and
      changes in the cervical extracellular matrix. It is likely that these are
      regulated by changes in periovulatory hormones, particularly estradiol. This
      study determined the effect of estradiol benzoate on the mRNA expression of
      cyclooxygenase-2 (COX-2) and the prostaglandin E receptors EP(2) and EP(4), the
      concentration of cervical hyaluronan, and the proportion of smooth muscle and
      collagen in the cervix of the hypogonadotrophic ovariectomized ewe (Ovis aries).
      Ovariectomized hypogonadotrophic ewes were given 100 microg estradiol benzoate,
      and their cervices were collected 0, 24, and 48 h thereafter to determine the
      expression of cervical COX-2, EP(2), and EP(4) mRNA by in situ hybridization, the
      concentration of hyaluronan by ELISA, and the proportion of smooth muscle and
      collagen by Masson's trichrome staining. Estradiol benzoate increased the mRNA
      expression of COX-2 and EP(4) within 24h after treatment (P<0.05), whereas EP(2)
      mRNA, hyaluronan, and the ratio of smooth muscle to collagen did not change
      within 48 h after treatment. The COX-2, EP(2), and EP(4) mRNA expression were
      greatest in the smooth muscle layers (P<0.05) and least in the luminal epithelium
      (P<0.05). In conclusion, we inferred that estradiol regulates cervical COX-2 and
      EP(4) mRNA expression and may regulate cervical relaxation via the synthesis of
      prostaglandin E(2) and activation of the PGE(2) receptors EP(2) and EP(4).

PMID- 20031196
TI  - Effect of equine chorionic gonadotropin on the efficiency of superovulation
      induction for in vivo and in vitro embryo production in the cat.
AB  - The effects of various dosages of equine chorionic gonadotropin (eCG) on
      superovulation induction for in vivo and in vitro embryo production were examined
      in stray cats (Felis catus). Cats (n=286) were allocated into five treatment
      groups with 0, 50, 100, 200, or 400 IU eCG, followed by 100 IU human chorionic
      gonadotropin (hCG). In vivo- and in vitro-produced blastocysts were obtained by
      artificial insemination (AI) and in vitro fertilization (IVF), somatic cell
      nucleus transfer (SCNT), or parthenogenetic activation (PA). The percentage of
      cats that developed mature follicles, the percentage of cats with collected
      embryos, and the mean number of in vivo blastocysts per cat were higher in the
      200 IU treatment group (43.9%, 31.8%, and 1.53, respectively) compared with those
      of the other groups (P<0.05). The percentage of follicular developed cats, the
      percentage of cumulus-expanded oocytes, and the mean number of collected cumulus
      oocyte complexes per cat in the 200 IU (56.7%, 67.8%, and 26.2, respectively) and
      400 IU (53.3%, 64.2%, and 26.7, respectively) groups were higher than those in
      the other groups (P<0.05). Furthermore, the percentage of in vitro-produced
      blastocyst per cleaved embryos and the average cell number of the blastocysts
      from IVF (52.7% and 125.8, respectively) was higher than those of the blastocysts
      from PA (30.1% and 85.2) and higher than those of the blastocysts from SCNT
      (15.3% and 37.5; P<0.05). In conclusion, the current study demonstrated that in
      vivo and in vitro embryo production were affected by the dosage of eCG; the best
      results were obtained with 200 IU.

PMID- 20031197
TI  - Language laterality in autism spectrum disorder and typical controls: a
      functional, volumetric, and diffusion tensor MRI study.
AB  - Language and communication deficits are among the core features of autism
      spectrum disorder (ASD). Reduced or reversed asymmetry of language has been found
      in a number of disorders, including ASD. Studies of healthy adults have found an
      association between language laterality and anatomical measures but this has not
      been systematically investigated in ASD. The goal of this study was to examine
      differences in gray matter volume of perisylvian language regions, connections
      between language regions, and language abilities in individuals with typical left
      lateralized language compared to those with atypical (bilateral or right)
      asymmetry of language functions. Fourteen adolescent boys with ASD and 20
      typically developing adolescent boys participated, including equal numbers of
      left- and right-handed individuals in each group. Participants with typical left
      lateralized language activation had smaller frontal language region volume and
      higher fractional anisotropy of the arcuate fasciculus compared to the group with
      atypical language laterality, across both ASD and control participants. The group
      with typical language asymmetry included the most right-handed controls and
      fewest left-handers with ASD. Atypical language laterality was more prevalent in
      the ASD than control group. These findings support an association between
      laterality of language function and language region anatomy. They also suggest
      anatomical differences may be more associated with variation in language
      laterality than specifically with ASD. Language laterality therefore may provide
      a novel way of subdividing samples, resulting in more homogenous groups for
      research into genetic and neurocognitive foundations of developmental disorders.

PMID- 20031198
TI  - Effect of low-elastic modulus liner and base as stress-absorbing layer in
      composite resin restorations.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of liner and
      base materials to reduce the stress resulting from polymerization shrinkage. The
      null hypothesis tested was that the presence of low-viscosity liner and base
      materials under the composite resin restoration reduces the polymerization
      shrinkage stress. METHODS: A quasi-three-dimensional photoelastic model of a
      second premolar with a class I preparation was restored using four experimental
      groups (n=7): RC, resin composite (Filtek Z250); FLRC, flowable liner (Filtek
      Flow)+resin composite restoration; VLRC, resin-modified glass-ionomer liner+resin
      composite restoration; and VBRC, resin-modified glass-ionomer base+resin
      composite restoration. The maximum shear stresses (tau(max)) were calculated
      along the adhesive interface in 13 predefined and standardized point locations.
      Data were submitted to one-way ANOVA, followed by a Tukey's post hoc test
      (p<0.05). RESULTS: A significant difference was found among the experimental
      groups (p=0.001); therefore, the null hypothesis was rejected. The mean maximum
      shear stress was: 38.0kPa for RC, 52.1kPa for FLRC, 72.8kPa for VLRC, and 90.2kPa
      for VBRC. The polymerization shrinkage stress level from least to greatest was:
      RC<FLRC<VLRC<VBRC. The overall stress distribution in class I restoration
      indicated that stresses were primarily accumulated at the cavosurface and
      internal line angles. SIGNIFICANCE: Using a flowable composite or resin-modified
      glass-ionomer as liner or base material under composite resin restoration
      increases the polymerization shrinkage stresses at the adhesive interface leading
      to a possible adhesive failure.

PMID- 20031200
TI  - C-reactive protein and cardiovascular risk: more fuel to the fire.

PMID- 20031201
TI  - A biodegradable polymer-based coating to control the performance of magnesium
      alloy orthopaedic implants.
AB  - Magnesium and its alloys may potentially be applied as degradable metallic
      materials in orthopaedic implantations due to their degradability and resemblance
      to human cortical bone. However, the high corrosion rate and accumulation of
      hydrogen gas upon degradation hinders its clinical application. In this study, we
      adopt a new approach to control the corrosion rate by coating a controllable
      polymeric membrane fabricated by polycaprolactone and dichloromethane onto
      magnesium alloys, in which the pore size was controlled during the manufacturing
      process. The addition of the polymeric membrane was found to reduce the
      degradation rate of magnesium, and the bulk mechanical properties were shown to
      be maintained upon degradation. The in-vitro studies indicated good
      cytocompatibility of eGFP and SaOS-2 osteoblasts with the polymer-coated samples,
      which was not observed for the uncoated samples. The in-vivo study indicated that
      the uncoated sample degraded more rapidly than that of the polymer-coated
      samples. Although new bone formation was found on both samples, as determined by
      Micro-CT, higher volumes of new bone were observed on the polymer-coated samples.
      Histological analysis indicated no inflammation, necrosis or hydrogen gas
      accumulation on either of the samples during degradation. Collectively, these
      data suggest that the use of polymeric membrane may be potentially applied for
      future clinical use.

PMID- 20031202
TI  - The effects of mixed MPEG-PLA/Pluronic copolymer micelles on the bioavailability
      and multidrug resistance of docetaxel.
AB  - A mixed micelle that comprised of MPEG-PLA (MPP) and Pluronic copolymers was
      developed for enhanced bioavailability and to overcome multidrug resistance of
      docetaxel in cancer therapy. The mixed micelles that sufficiently solubilized
      docetaxel were evaluated for the effect of Pluronic copolymers weight ratio on
      the mixed micelles with respect to drug loading and drug release. In vitro, cell
      viability and cytotoxicity studies in KB and KBv cells revealed that the mixed
      micellar formulations were more potent than the commercial docetaxel formulation
      (Taxotere). In vivo pharmacokinetics study in rats showed that the mixed micelles
      significantly enhanced the bioavailability of docetaxel (3.6 fold) than Taxotere.
      Moreover, antitumor activity assessed in KBv cancer xenograft BALB/C nude mice
      models showed that the mixed micelles significantly reduced the tumor size than
      the control (Taxotere). Clear differences in the intracellular uptake of
      docetaxel between MPP and mixed micelles were observed using confocal laser
      scanning microscopy. This study presents not only a new micelle structure for a
      diblock-triblock copolymer system, but also a method for enhanced bioavailability
      of docetaxel and to overcome some of the limitations on its multidrug resistance
      in cancer therapy.

PMID- 20031203
TI  - Enhanced drug targeting by attachment of an anti alphav integrin antibody to
      doxorubicin loaded human serum albumin nanoparticles.
AB  - Specific transport of anti-cancer drugs into tumor cells may result in increased
      therapeutic efficacy and decreased adverse events. Expression of alphavbeta3
      integrin is enhanced in various types of cancer and monoclonal antibodies (mAbs)
      directed against alphavbeta3 integrins hold promise for anti-cancer therapy.
      DI17E6 is a monoclonal antibody directed against alphav integrins that inhibits
      growth of melanomas in vitro and in vivo and inhibits angiogenesis due to
      interference with alphavbeta3 integrins. Here, DI17E6 was covalently coupled to
      human serum albumin nanoparticles. Resulting nanoparticles specifically targeted
      alphavbeta3 integrin positive melanoma cells. Moreover, doxorubicin loaded DI17E6
      nanoparticles showed increased cytotoxic activity in alphavbeta3-positive
      melanoma cells than the free drug. Therefore, DI17E6-coupled human serum albumin
      nanoparticles represent a potential delivery system for targeted drug transport
      into alphavbeta3-positive cells.

PMID- 20031204
TI  - Engineering cardiac tissue in vivo from human adipose-derived stem cells.
AB  - Cardiac tissue engineering offers promise as a surgical approach to cardiac
      repair, but requires an adequate source of cardiomyocytes. Here we evaluate the
      potential for generating human cardiac muscle cells in vivo from adipose-derived
      stem cells (ASC) by co-implanting in a vascularised tissue engineering chamber
      with inducing rat cardiomyocytes (rCM). Co-implantation (ASC-rCM) was compared
      with rCM or ASC controls alone after 6 weeks. Immunostaining using human nucleus
      specific antibody and cardiac markers revealed several fates for ASC in the
      chamber; (1) differentiation into cardiomyocytes and integration with co
      implanted rCM; (2) differentiation into smooth muscle cells and recruitment into
      vascular structures; (3) adipogenic differentiation. ASC-rCM and ASC groups grew
      larger tissue constructs than rCM alone (212+/-25 microl, 171+/-16 microl vs.
      137+/-15 microl). ASC-rCM and rCM groups contracted spontaneously at up to 140
      bpm and generated a 10-15-fold larger volume of cardiac muscle (14.5+/-4.8 microl
      and 18.5+/-2.6 microl) than ASC alone group (1.3+/-0.5 microl). Vascular volume
      in ASC-rCM group was twice that of the rCM group (28.7+/-5.0 microl vs. 14.8+/
      1.8 microl). The cardiac tissue engineered by co-implanting human ASC with
      neonatal rCM showed in vivo plasticity of ASC and their cardiomyogenic potential
      in tissue engineering. ASC contribution to vascularisation also promoted the
      growth of engineered tissue, confirming their utility in this setting.

PMID- 20031205
TI  - Chorioamnionitis--a complex pathophysiologic syndrome.
AB  - Chorioamnionitis, inflammation of the amniochorionic membrane (fetal membranes)
      is a very common disease but a complex syndrome associated with pregnancy. It
      presents a clinical impasse due to lack of knowledge of specific etiologies
      associated with this condition making confident clinical interventions difficult.
      Recent reports provide insight into genetic, epigenetic, behavioral,
      psychosocial, molecular and pathophysiological factors that are associated with
      chorioamnionitis. However, a coordinated approach in understanding causality and
      lack of early indicators (clinical and biomarkers) has hampered gaining knowledge
      about the disease status preventing proper intervention. Several reviews have
      provided in-depth analysis of the histologic and clinical evidence associated
      with chorioamnionitis. In this review, we provide a novel perspective on
      chorioamnionitis based on recent evidences from scientific literature on
      inflammation, apoptosis and genetics.

PMID- 20031206
TI  - Estrogen-regulated expression and distribution of Id-1 in the mouse uterus.
AB  - Id genes are involved in proliferation and differentiation in various cell types.
      However, it remains to be fully investigated how Id genes are regulated in highly
      dynamic uterine tissue. Using cDNA microarray, we previously observed that Id-1
      was upregulated in uteri from ovariectomized (OVX) mice exposed to 17beta
      estradiol (E2). Here, we further examined the expression pattern of Id-1 and its
      regulation of by E2 and progesterone (P4) in the mouse uterus. Increased Id-1
      transcripts in OVX mice uterus exposed to E2 were efficiently reduced by
      pretreatment with ICI 182,780 (an antagonist for nuclear estrogen receptor),
      suggesting that E2 induced expression of Id-1 is mediated via classical estrogen
      receptor (ER). In contrast, P4 treatment did not enhance or antagonize the action
      of E2 on Id-1 expression. Laser capture microdissection revealed that Id-1 is
      exclusively expressed in luminal epithelial cells. Notably, Id-1 was
      significantly upregulated at implantation sites on day 4.5 of pregnancy due to
      strong expression of Id-1 in blastocyst stage embryos. The present results show
      that the expression of Id-1 in the mouse uterus is tightly regulated by E2 via
      classical ER genomic pathway, not P4 suggesting an important role in uterine
      physiological events such as the estrous cycle and implantation process.

PMID- 20031207
TI  - Ethanol exposure selectively alters beta-endorphin content but not [3H]-DAMGO
      binding in discrete regions of the rat brain.
AB  - The dopaminergic mesocorticolimbic system plays an important role in the
      reinforcing effects of ethanol. Opioid peptides modulate the activity of this
      system and have been suggested to mediate, at least in part, the reinforcing
      properties of ethanol. Thus, beta-endorphin (beta-END) could participate in the
      development of ethanol reinforcement and addiction. The aim of this work was to
      investigate the acute and chronic ethanol effects on beta-END content in regions
      of the mesolimbic system and to examine if chronic ethanol treatment alters
      ligand binding to mu opioid receptor (muOR). Male Wistar rats received a single
      acute ethanol dose of 2.5 g/kg or water by intra-gastric administration. For
      chronic ethanol treatment experiments, one group of rats was given ethanol (10%
      v/v solution) to drink, two groups were given equivalent volumes of sucrose
      (14.14% isocaloric solution) or water, respectively, and a fourth group had ad
      libitum access to food and water. Treatment was followed for 4 weeks. Beta
      endorphin content in brain regions was quantified by radioimmunoassay and ligand
      binding studies to muOR were performed by quantitative autoradiography using 8 nM
      [(3)H]-DAMGO as radioligand. Acute ethanol decreased beta-END content in the
      hypothalamus (26%) 1h after administration. No ethanol effects were observed in
      the midbrain, ventral tegmental area, substantia nigra, nucleus accumbens,
      nucleus accumbens-septum and prefrontal cortex. Chronic ethanol treatment neither
      changed beta-END levels nor [(3)H]-DAMGO binding to mu opioid receptors in any of
      the regions studied. However, beta-END levels in the sucrose group were
      significantly increased in the nucleus accumbens and substantia nigra, in
      comparison to all other groups. These findings suggest that different neural
      mechanisms and specific brain regions may be involved in the reinforcing effects
      of ethanol and sucrose.

PMID- 20031208
TI  - VPAC1 receptor binding site: contribution of photoaffinity labeling approach.
AB  - The vasoactive intestinal peptide (VIP) is a prominent 28 aminoacid neuropeptide
      with wide distribution in both central and peripheral nervous systems, where it
      plays important regulatory role in many physiological processes. VIP has a large
      spectrum of biological functions including exocrine secretions, hormone release,
      foetal development, immune response and also exerts beneficial effect in neuro
      degenerative and inflammatory diseases. Few years ago, it has been shown that VIP
      can be a promising anti-inflammatory agent. VIP mechanisms of action implicate
      two sub-types of receptors (VPAC1 and VPAC2) which are members of class B
      receptors belonging to the super-family of G protein-coupled receptor (GPCR).
      Because, VPAC1 receptor plays an important role in the modulation of the ant
      inflammatory response and represent an archetype of class B GPCR, we have
      extensively studied the structure-function relationship of this receptor, which
      allowed us to define the molecular basis of that receptor in term of affinity,
      specificity, desensitization and coupling to adenylyl cyclase. Those studies
      showed the crucial role of the N-terminal ectodomain (N-ted) of VPAC1 receptor in
      VIP binding. Using different techniques including photoaffinity labeling, NMR,
      molecular modeling and molecular dynamic simulation, it has been possible to
      define how VIP interacts with its receptor. We have shown that most of the VIP
      molecule, 1-28 (alpha-helix) sequence, tightly binds the N-ted part of the
      receptor which is himself structured as a <<Sushi>> domain. In contrast, the N
      terminal part of the specific antagonist PG97-269 is in physical contact with the
      N-ted but in different region. These studies define the molecular mechanism
      implicated in the activation of class B VPAC1 receptor and should allow the
      development of new VIP pharmacology using rational synthesis of agonist
      molecules.

PMID- 20031199
TI  - C-reactive protein concentration and risk of coronary heart disease, stroke, and
      mortality: an individual participant meta-analysis.
AB  - BACKGROUND: Associations of C-reactive protein (CRP) concentration with risk of
      major diseases can best be assessed by long-term prospective follow-up of large
      numbers of people. We assessed the associations of CRP concentration with risk of
      vascular and non-vascular outcomes under different circumstances. METHODS: We
      meta-analysed individual records of 160 309 people without a history of vascular
      disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease
      outcomes) from 54 long-term prospective studies. Within-study regression analyses
      were adjusted for within-person variation in risk factor levels. RESULTS: Log(e)
      CRP concentration was linearly associated with several conventional risk factors
      and inflammatory markers, and nearly log-linearly with the risk of ischaemic
      vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart
      disease per 1-SD higher log(e) CRP concentration (three-fold higher) were 1.63
      (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27
      1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and
      1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for
      vascular mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular
      mortality. RRs were largely unchanged after exclusion of smokers or initial
      follow-up. After further adjustment for fibrinogen, the corresponding RRs were
      1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemic
      stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non
      vascular mortality. INTERPRETATION: CRP concentration has continuous associations
      with the risk of coronary heart disease, ischaemic stroke, vascular mortality,
      and death from several cancers and lung disease that are each of broadly similar
      size. The relevance of CRP to such a range of disorders is unclear. Associations
      with ischaemic vascular disease depend considerably on conventional risk factors
      and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical
      Research Council, BUPA Foundation, and GlaxoSmithKline.

PMID- 20031209
TI  - Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral
      blood in patients with myelodysplastic syndromes.
AB  - Wilms tumor gene (WT1) mRNA expression in peripheral blood cells was examined in
      80 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
      transformed from MDS. Serum anti-WT1 antibody titers were also determined in 45
      patients. Their long-term follow-up showed that the survival rate became worse as
      the WT1 mRNA level increased. In particular, a high WT1 mRNA level was a strong
      predictor of a short time to AML transformation even if adjusted by the
      International Prognostic Scoring System category. Moreover, high values of anti
      WT1 antibody were an independent predictor of longer survival. These data may
      justify therapeutic strategies targeting WT1 molecules in MDS.

PMID- 20031210
TI  - Molecular characterization and prognostic significance of FLT3 in CML
      progression.
AB  - To characterize the molecular mechanisms involved in the transition from the
      chronic phase to blast crisis in chronic myelogenous leukemia (CML), gene
      expression profiles of leukemic cells from patients in the chronic and blast
      crisis phases were analyzed using an 8.7K cDNA chip and real-time PCR. A
      transient transfection analysis was conducted to evaluate the role of FLT3, which
      was significantly upregulated in the blast crisis patients. Abl and c-Kit
      induction was detected in K562 cells transfected with FLT3 cDNA (K562/FLT3), and
      Abl and c-Kit levels were reduced in K562/FLT3 cells transfected with FLT3-siRNA
      (K562/FLT3-siRNA). The induction of FLT3 in CML cells attenuated imatinib-induced
      apoptosis. The opposite effect was observed in K562/FLT3-siRNA cells. An
      increased level of cleaved PARP and decreased level of pro-caspase 3 were noted
      when K562/FLT3-siRNA cells were treated with imatinib. These findings indicate
      that FLT3 is associated with disease progression, despite imatinib therapy. These
      results may help in the prediction of disease progression in CML patients and the
      development of more appropriate therapeutic modalities.

PMID- 20031211
TI  - Micro-RNA-15a and micro-RNA-16 expression and chromosome 13 deletions in multiple
      myeloma.
AB  - We have used copy number variation (CNV) analysis with SNP mapping arrays for
      miRNA-15a and miRNA-16-1 expression analysis in patients with multiple myeloma
      (MM) with or without deletion of chromosome 13q14. MiRNA-15a and miRNA-16 display
      a range of expression patterns in MM patients, independent of the chromosome 13
      status. These findings suggest that genes other than miR-15a and miR-16 may
      explain the prognostic significance of 13q14 deletions.

PMID- 20031212
TI  - Unrelated donor umbilical cord blood transplantation versus unrelated donor bone
      marrow transplantation in adult and pediatric patients: A meta-analysis.
AB  - The effect of unrelated donor bone marrow transplantation (UBMT) and unrelated
      donor cord blood transplantation (UCBT) on the outcome of patients with
      hematological diseases remains controversial. We conducted a meta-analysis using
      data from controlled clinical trials comparing UCBT to UBMT in patients
      undergoing hematopoietic stem cell transplantation. Pooled comparisons of studies
      of UCBT and UBMT in children found that the incidence of chronic graft-versus
      host disease (GVHD) was lower with UCBT (relative risk [RR]=0.41; 95% confidence
      interval [CI] (0.25, 0.68)), and the incidence of grades II-IV aGVHD was also
      significantly different (RR=0.69; 95% CI (0.55, 0.86)). The incidence of relapse
      was also lower with UCBT (RR=0.72; 95% CI (0.59, 0.87)). There was no difference
      in OS in children when studies were pooled (Hazard ratio [HR]=1.25; 95% CI (0.87,
      1.78)). For adults, OS (HR=1.26; 95% CI (1.13, 1.40)) was statistically
      different. Thus, UCBT led to inferior outcomes than UBMT in adults.

PMID- 20031213
TI  - The use of marine benthic diatoms in a growth inhibition test with spiked whole
      sediment.
AB  - The benthic diatom Cylindrotheca closterium was exposed to whole-sediment spiked
      with the synthetic surfactant Linear Alkylbenzene Sulphonate (LAS), as commercial
      mixture or individual homologues (C10-LAS, C11-LAS or C12-LAS). Separately, the
      diatoms were exposed to C12-LAS in a water-only system. The algal growth was
      determined after 72 h. The 72-h ErC50 values ranged from <or=4 to 29 mg/kg
      sediment, suggesting that C. closterium was sensitive to LAS. The outcomes were
      reproducible with a variation factor lower than 3, showing the reproducibility of
      the method. The test set up was cost effective, used little bench space and
      employed a micro-phytobenthos species that fulfilled most of the criteria for a
      suitable test species in sediment systems. The 72-h ErC50 obtained in a water
      only system (0.141 mg/L) was ca. 2 orders of magnitude lower (0.002 mg/L). This
      was likely due to an indirect effect of the use of fresh sediment.

PMID- 20031214
TI  - Photobiont diversity in lichens from metal-rich substrata based on ITS rDNA
      sequences.
AB  - The photobiont is considered as the more sensitive partner of lichen symbiosis in
      metal pollution. For this reason the presence of a metal tolerant photobiont in
      lichens may be a key factor of ecological success of lichens growing on metal
      polluted substrata. The photobiont inventory was examined for terricolous lichen
      community growing in Cu mine-spoil heaps derived by historical mining. Sequences
      of internal transcribed spacer (ITS) were phylogenetically analyzed using maximum
      likelihood analyses. A total of 50 ITS algal sequences were obtained from 22
      selected lichen taxa collected at three Cu mine-spoil heaps and two control
      localities. Algae associated with Cladonia and Stereocaulon were identified as
      members of several Asterochloris lineages, photobionts of cetrarioid lichens
      clustered with Trebouxia hypogymniae ined. We did not find close relationship
      between heavy metal content (in localities as well as lichen thalli) and
      photobiont diversity. Presence of multiple algal genotypes in single lichen
      thallus has been confirmed.

PMID- 20031215
TI  - Biochemical, metabolic, and behavioural responses and recovery of Daphnia magna
      after exposure to an organophosphate.
AB  - The responses of various suborganismal and organismal endpoints of Daphnia magna
      to pulse exposure to sublethal levels of the organophosphate paraoxon-methyl were
      compared. The changes and recovery of biochemical, metabolic, and behavioural
      variables, as well as physiological responses, were observed. The cholinesterase
      (ChE), filtration, and swimming activities were all affected in a concentration
      dependent manner, and these effects reached significance at concentrations of
      1.0, 1.5, and 0.7 microg L(-1), respectively. The levels of these variables
      recovered significantly after detoxification for 24h in clean medium. ChE and
      swimming activities were affected significantly by lower concentrations of
      paraoxon-methyl than filtration activity, which had the same threshold as the
      physiological responses ((15)N abundance and body size). This study showed that
      among the parameters studied, swimming activity was the most sensitive, whereas
      changes in filtration activity had the most significant physiological
      consequences, and were therefore important in terms of effects propagation to the
      population level.

PMID- 20031216
TI  - RT-PCR evaluation for identification and sequence analysis of foot-and-mouth
      disease serotype O from 2006 to 2007 in Punjab, Pakistan.
AB  - FMD clinically positive 250 tissue samples (mouth and hoof epithelium and vesicle
      swabs, tongue tissue) and 175 secretion samples (milk, saliva, serum, plasma)
      were evaluated by RT-PCR for the diagnosis of FMD with different pair of
      universal and serotype-specific primers from 2006 to 2007 in Punjab, Pakistan.
      Universal primer pair P1/P2 from VP1 gene detected FMD in 182 out of 250 (72.8%)
      tissues and 92 out of 175 (52.6%) secretion samples, while universal primer 1F/1R
      from 5'UTR region detected FMD in 218 out of 250 (87.2%) tissues and 142 out of
      175 (81.1%) secretion samples. 1F/1R proved better than the P1/P2 primer pair for
      primary diagnosis of FMD, direct from the clinical positive samples. Direct
      sequencing of the universal primer pair P1/P2 revealed that O serotype of FMD was
      circulating in this region. O serotype of FMD was detected with O-1C(ARS4)/PNK
      61, AU(O)/AU(rev), AU(O)/PNK61 primer pairs, these primer pairs also compared
      with each other. AU(O)/AU(rev) and AU(O)/PNK61 detected O serotype of FMD in
      88.9% tissue and swab (mouth and hoof vesicle swabs) samples and 71.9% different
      secretion (milk, saliva, serum, plasma) samples, while O-1C(ARS4)/PNK 61 detected
      48.1% tissue and swab (mouth and hoof vesicle swabs) samples and 37.5% different
      secretion (milk, saliva, serum, plasma) samples. AU(O)/AU(rev), AU(O)/PNK61
      primer pairs detected 40.8% more tissue and swab samples, while these pairs
      detected 34.4% more secretion samples. Cloning of PCR product of AU(O)/AU(rev)
      VP1 gene and sequencing for phylogenetic studies revealed that O serotype of FMD
      circulating in Punjab, Pakistan was genetically very diverse from the 'O'
      serotype in Middle East and Europe. The dendrogram showed that Pakistan 'O'
      serotype was very much similar genetically to its neighbor countries (Sri Lanka,
      India, Iran, Iraq, and China) and PanAsia 1 lineage which caused 2001-outbreak in
      UK and 1994-outbreak in Saudi Arabia, etc.

PMID- 20031217
TI  - Greenwich, time and 'the line'.
AB  - Ask most visitors to the Royal Observatory, Greenwich, why they have come and
      they will tell you that they want to stand on 'the line'. Press them further and
      they might add something about standing astride longitude zero, one foot in the
      eastern hemisphere and one in the west. Few know how the Prime Meridian of the
      world comes to pass through Greenwich, or even realise that the line is there
      because of the observatory, rather than vice versa. But the line, of course, has
      a history, as does the public's response to it.

PMID- 20031220
TI  - Detection of bacterial endosymbionts in clinical acanthamoeba isolates.
AB  - PURPOSE: To determine the presence of 4 clinically relevant bacterial
      endosymbionts in Acanthamoeba isolates obtained from patients with Acanthamoeba
      keratitis (AK) and the possible contribution of endosymbionts to the pathogenesis
      of AK. DESIGN: Experimental study. PARTICIPANTS: Acanthamoeba isolates (N = 37)
      recovered from the cornea and contact lens paraphernalia of 23 patients with
      culture-proven AK and 1 environmental isolate. METHODS: Acanthamoeba isolates
      were evaluated for the presence of microbial endosymbionts belonging to the
      bacterial genera Legionella, Pseudomonas, Mycobacterium, and Chlamydia using
      molecular techniques (polymerase chain reaction and sequence analysis,
      fluorescence in situ hybridization) and transmission electron microscopy. Corneal
      toxicity and virulence of Acanthamoeba isolates with and without endosymbionts
      were compared using a cytopathic effect (CPE) assay on human corneal epithelial
      cells in vitro. Initial visual acuity, location and characteristics of the
      infiltrate, time to detection of the infection, and symptom duration at
      presentation were evaluated in all patients. MAIN OUTCOME MEASURES: Prevalence
      and potential pathobiology of bacterial endosymbionts detected in Acanthamoeba
      isolates recovered from AK. RESULTS: Twenty-two (59.4%) of the 38 cultures
      examined contained at least 1 bacterial endosymbiont. One isolate contained 2
      endosymbionts, Legionella and Chlamydia, confirmed by fluorescence in situ
      hybridization. Corneal toxicity (CPE) was significantly higher for Acanthamoeba
      hosting endosymbionts compared with isolates without endosymbionts (P<0.05).
      Corneal pathogenic endosymbionts such as Pseudomonas and Mycobacterium enhanced
      Acanthamoeba CPE significantly more than Legionella (P<0.05). In the presence of
      bacterial endosymbionts, there was a trend toward worse initial visual acuity
      (P>0.05), central location (P<0.05), absence of radial perineuritis (P<0.05),
      delayed time to detection (P>0.05), and longer symptom duration at presentation
      (P>0.05). CONCLUSIONS: Most Acanthamoeba isolates responsible for AK harbor 1 or
      more bacterial endosymbionts. The presence of endosymbionts enhances the corneal
      pathogenicity of Acanthamoeba isolates and may impact detection time and clinical
      features of AK.

PMID- 20031218
TI  - Channel catfish soluble FcmuR binds conserved linear epitopes present on Cmu3 and
      Cmu4.
AB  - A linear epitope on catfish IgM has been identified as the docking site for the
      catfish soluble FcmuR (IpFcRI). Western blot analyses and latex bead binding
      assays identified the consensus octapeptide motif FxCxVxHE located at the second
      cysteine that forms the intrachain disulfide bond of the catfish Cmu3 and Cmu4
      immunolglobulin (Ig) domains as the IpFcRI binding sites. Furthermore, molecular
      modeling of catfish Cmu3 and Cmu4 confirmed that the octapeptide in both of these
      domains is accessible for IpFcRI interactions. In addition, since this
      octapeptide motif is also found in other vertebrate Ig domains, IpFcRI binding to
      Ig heavy (H) and light (L) chains from rainbow trout, chicken, mouse, rabbit, and
      goat were examined by Western blot analyses and latex bead binding assays. IpFcRI
      readily bound reduced rainbow trout (Igmu), chicken (Ignu), mouse (Igmu,
      Iggamma1, Iggamma2a, Iggamma2b, and Igalpha), rabbit (Igmu and Iggamma) and goat
      (Iggamma) IgH chains, and mouse Igkappa and Iglambda, and chicken Iglambda IgL
      chains. IpFcRI also bound mouse IgM, IgA and IgG subclasses when examined under
      native conditions.

PMID- 20031221
TI  - Acute retinal necrosis: the effects of intravitreal foscarnet and virus type on
      outcome.
AB  - PURPOSE: To study the effects of intravitreal foscarnet and the clinical
      differences between varicella zoster virus (VZV) and herpes simplex virus (HSV)
      induced acute retinal necrosis (ARN). DESIGN: Retrospective comparative case
      series. PARTICIPANTS: Eighty-one eyes of 74 patients. METHODS: A retrospective
      case note analysis was performed in 2 tertiary referral centers. MAIN OUTCOME
      MEASURES: Presenting and final visual acuity, and progression to retinal
      detachment. RESULTS: Thirty-three eyes had HSV-ARN and 48 had VZV-ARN. The
      average age for HSV-ARN was 34 years and 51 for VZV-ARN (P<0.001). Visual acuity
      on presentation was similar (P = 0.48), but a larger proportion had better vision
      (> or =20/60) in the HSV-ARN group (52%) than the VZV-ARN group (35%). A greater
      proportion of eyes with poor vision (< or =20/200) was found at the 12-month
      follow-up in the VZV-ARN group (60%) compared with the HSV-ARN group (35%). A
      greater degree of visual loss in the VZV-ARN group (0.4 logarithm of the minimum
      angle of resolution [logMAR]) compared with the HSV-ARN group (0.04 logMAR) was
      detected (P = 0.016). Retinal detachment was 2.5-fold more common in VZV-ARN
      (62%) compared with HSV-ARN (24%). When comparing eyes treated with (n = 56) and
      without (n = 25) intravitreal foscarnet, there was a 40% lower rate in retinal
      detachment (53.6% vs 75.0%) for VZV-ARN (P = 0.23). The numbers with HSV-ARN were
      too small for analysis. CONCLUSIONS: The results support the difference of
      outcome in HSV-ARN and VZV-ARN. Therefore, viral identification serves as a key
      to predicting outcome in these patients. Intravitreal foscarnet seems to be a
      useful adjunct for the treatment of ARN in that it reduced rate of retinal
      detachment.

PMID- 20031219
TI  - Exploring peptide mimics for the production of antibodies against discontinuous
      protein epitopes.
AB  - Peptide "mimics" (mimotopes) of linear protein epitopes and carbohydrate epitopes
      have been successfully used as immunogens to elicit cross-reactive antibodies
      against their cognate epitopes; however, immunogenic mimicry has been difficult
      to achieve for discontinuous protein epitopes. To explore this, we developed from
      phage-displayed peptide libraries optimized peptide mimics for three well
      characterized discontinuous epitopes on hen egg lysozyme and horse cytochrome c.
      The peptides competed with their cognate antigens for antibody binding, displayed
      affinities in the nM range, and shared critical binding residues with their
      native epitopes. Yet, while immunogenic, none of the peptides elicited antibodies
      that cross-reacted with their cognate antigens. We analyzed the 3-D structure of
      the site within each discontinuous epitope that shared critical binding residues
      with its peptide mimic, and observed that in each case it formed a ridge-like
      patch on the epitope; in no case did it cover most or all of the epitope. Thus,
      the peptides' lack of immunogenic mimicry could be attributed to their inability
      to recapitulate the topological features of their cognate epitopes. Our results
      suggest that direct peptide immunizations are not a practical strategy for
      generating targeted antibody responses against discontinuous epitopes.

PMID- 20031222
TI  - The incidence of retinal vein occlusion in the ocular hypertension treatment
      study.
AB  - OBJECTIVE: To determine the incidence of retinal vein occlusion (RVO) in the
      Ocular Hypertension Treatment Study (OHTS). DESIGN: Retrospective analysis of
      data from a randomized clinical trial. PARTICIPANTS: We included 1636 ocular
      hypertensive participants with a mean follow-up of 9.1 years. Participants in the
      medication and observation groups were managed according to their original
      randomization assignment until June 1, 2002. At that time, the observation
      participants were offered ocular hypotensive treatment. Data to July 1, 2005, are
      included in this report. METHODS: Occurrences of RVO in study participants,
      categorized as branch, central or hemicentral vein occlusion, were documented.
      Potential RVO events were identified by a keyword search of Adverse Event
      Reports, the Optic Disc Reading Center database, Endpoint Committee reviews, and
      by response to a written request for information sent to each clinical site. To
      confirm a potential RVO, the complete OHTS chart was reviewed. Statistical
      analyses included t tests, chi-square tests and Cox proportional hazards models.
      MAIN OUTCOME MEASURES: Incidence of RVO. RESULTS: Twenty-six RVOs-5 branch, 14
      central, and 7 hemicentral RVOs-were confirmed in 23 participants (15 observation
      and 8 medication). The 10-year cumulative incidence of RVO was 2.1% in the
      observation group and 1.4% in the medication group (P = 0.14; log-rank test). At
      baseline, participants who later developed a RVO were significantly older (65.1
      vs 55.3 years; P = 0.01), and had greater horizontal cup-to-disc ratios (P =
      0.0004). CONCLUSIONS: Although the incidence of RVO was higher in the observation
      group than the medication group, this difference did not attain significance.
      Consistent with some previous studies, older age and greater cup-to-disc ratio
      were associated with the development of RVO.

PMID- 20031224
TI  - Are myopic eyes less likely to have diabetic retinopathy?
AB  - PURPOSE: Eyes with myopia may be less likely to develop diabetic retinopathy
      (DR). The relationship between refractive error, ocular biometry, and DR
      therefore was investigated. DESIGN: Population-based, cross-sectional study.
      PARTICIPANTS: Persons with diabetes from the Singapore Malay Eye Study (SiMES).
      METHODS: Diabetes mellitus was defined as random glucose of 11.1 mmol/l or more,
      use of diabetic medication, or a physician diagnosis of diabetes. Spherical
      equivalent refraction (SE) was assessed using an autokeratorefractometer and
      subjective refraction. Axial length (AL) and anterior chamber depth (ACD) were
      measured by IOLMaster (Carl Zeiss Meditec AG, Jena, Germany). Diabetic
      retinopathy was graded from retinal photographs. MAIN OUTCOME MEASURES: Any DR
      was defined by characteristic lesions defined by the Early Treatment Diabetic
      Retinopathy Study (ETDRS); moderate DR by ETDRS retinopathy severity scores of 43
      or higher; and vision-threatening retinopathy by severe nonproliferative
      retinopathy, proliferative DR, or clinically significant macular edema. RESULTS:
      Of 3280 adult Malay participants (78.7% response), 629 persons with diabetes
      contributed to this analysis. In multivariate analyses adjusting for age, gender,
      education, height, cataract, hypertension, hemoglobin A1c, and other factors,
      eyes with myopic SE were less likely to have any DR (odds ratio [OR], 0.90; 95%
      confidence interval [CI], 0.84-0.96; P = 0.002, per 1-diopter [D] decrease),
      moderate DR (OR, 0.83; 95% CI, 0.73-0.93; P = 0.001, per 1-D decrease), and
      vision-threatening DR (OR, 0.77; 95% CI, 0.67-0.88; P<0.001, per 1-D decrease).
      Eyes with longer AL were less likely to have any DR (OR, 0.86; 95% CI, 0.75-0.99;
      P = 0.041, per 1-mm increase), moderate DR (OR, 0.80; 95% CI, 0.62-1.05; P =
      0.11, per 1-mm increase), and vision-threatening DR (OR, 0.63; 95% CI, 0.40-0.99;
      P = 0.044, per mm increase). Eyes with deeper ACD were less likely to have
      moderate DR (OR, 0.32; 95% CI, 0.16-0.64; P = 0.001, per 1-mm increase) and
      vision-threatening DR (OR, 0.14; 95% CI, 0.06-0.36; P = 0.001, per 1-mm
      increase). CONCLUSIONS: Myopic refraction and longer AL are associated with a
      lower risk of DR, particularly vision-threatening retinopathy, without any
      evidence of a threshold.

PMID- 20031223
TI  - Cyclosporine for ocular inflammatory diseases.
AB  - PURPOSE: To evaluate the clinical outcomes of cyclosporine treatment for
      noninfectious ocular inflammation. DESIGN: Retrospective cohort study.
      PARTICIPANTS: A total of 373 patients with noninfectious ocular inflammation
      managed at 4 tertiary ocular inflammation clinics in the United States observed
      to use cyclosporine as a single noncorticosteroid immunosuppressive agent to
      their treatment regimen, between 1979 and 2007 inclusive. METHODS: Participants
      were identified from the Systemic Immunosuppressive Therapy for Eye Diseases
      Cohort Study. Demographic and clinical characteristics, including dosage of
      cyclosporine and main outcome measures, were obtained for every eye of every
      patient at every visit via medical record review by trained expert reviewers.
      MAIN OUTCOME MEASURES: Control of inflammation, sustained control after reducing
      corticosteroid dosages, and discontinuation of therapy because of toxicity.
      RESULTS: Of the 373 patients (681 eyes) initiating cyclosporine monotherapy,
      33.4% by 6 months and 51.9% by 1 year gained sustained, complete control of
      inflammation over at least 2 visits spanning at least 28 days. Approximately 25%
      more improved to a level of slight inflammatory activity by each of these time
      points. Corticosteroid-sparing success (completely controlled inflammation for at
      least 28 days with prednisone < or = 10 mg/day) was achieved by 22.1% by 6 months
      and 36.1% within 1 year. Toxicity led to discontinuation of therapy within 1 year
      by 10.7% of the population. Patients aged more than 55 years were more than 3
      fold more likely to discontinue therapy because of toxicity than patients aged 18
      to 39 years. Doses of 151 to 250 mg/day tended to be more successful than lower
      doses and were not associated with a higher discontinuation for toxicity rate;
      higher doses did not seem to offer a therapeutic advantage. CONCLUSIONS:
      Cyclosporine, with corticosteroid therapy as indicated, was modestly effective
      for controlling ocular inflammation. Our data support a preference for
      cyclosporine adult dosing between 151 and 250 mg/day. Although cyclosporine was
      tolerated by the majority of patients, toxicity was more frequent with increasing
      age; alternative agents may be preferred for patients aged more than 55 years.

PMID- 20031226
TI  - High-resolution imaging of the human retina in vivo after scatter
      photocoagulation treatment using a semiautomated laser system.
AB  - PURPOSE: To image the ultrastructural morphology of retinal laser effects and
      their healing response in vivo using spectral domain optical coherence tomography
      (SD-OCT). DESIGN: Prospective, interventional study. PARTICIPANTS: Ten patients
      undergoing panretinal photocoagulation for proliferative diabetic retinopathy.
      METHODS: Panretinal photocoagulation (PRP) was performed using a semiautomated
      patterned scanning laser system providing a raster of effects with homogenous
      intensity. Retinal morphology and localization of effects owing to laser-tissue
      interaction were imaged at 1 day, 1 week, and at monthly intervals for 6 months.
      The characteristic, specific structural changes during the healing process were
      followed over time using an SD-OCT device (Spectralis OCT) allowing for high
      resolution raster scanning of the entire lesion pattern with identification of
      identical retinal sites (tracking modality). MAIN OUTCOME MEASURES: Retinal
      morphology and localization of effects of photocoagulation on SD-OCT images.
      RESULTS: At day 1 after PRP, the photocoagulation effects were sharply delineated
      from the surrounding unaffected retina and all spots seemed to be identical in
      size and location. The area of tissue destruction was confined to the outer
      retinal layers, extending from the outer nuclear layer (ONL) to the retinal
      pigment epithelium (RPE). At 1 week, images showed a progressive loss of the
      affected outer retinal layers, namely, the ONL and the outer plexiform layer.
      Concomitant distortion of the inner nuclear and plexiform layers generated a
      pattern of "archways" between adjacent laser spots. The photoreceptor layers
      (PRL) seemed to be eliminated in the photocoagulated area, particularly at the
      borders of each lesion. The lesion center contained a condensed RPE and PRL
      segment. The ONL recovered partially, but the PRL inner and outer segments
      remained absent. During the long-term follow-up, RPE cells migrated to the center
      of the lesion, forming a hyperplastic scar. CONCLUSIONS: The characteristic
      morphology of retinal photocoagulation effects in vivo and over time was
      identified for the first time in human eyes using SD-OCT. The OCT imaging
      demonstrated a well-defined reproducible area of destruction confined to the
      outer retinal layers. Healing proceeded as the condensation of the RPE and PRL in
      the lesion center.

PMID- 20031225
TI  - Central and peripheral visual impairment and the risk of falls and falls with
      injury.
AB  - OBJECTIVE: To evaluate whether central (CVI) and peripheral visual impairment
      (PVI) are independent risk factors for falls and falls with injury 4 years later.
      DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A population
      based sample of 3203 adult Latinos. METHODS: Baseline presenting binocular
      central distance acuity was measured and impairment was classified as mild (20/40
      20/63) or moderate/severe (<or=20/80). Peripheral visual impairment was
      classified as mild (-6 dB < mean deviation < -2 dB in worse eye), moderate/severe
      (mean deviation <or=-6 dB in worse eye). MAIN OUTCOME MEASURES: Falls and falls
      with injury in the past 12 months were assessed by self-report at the 4-year
      follow-up visit. RESULTS: Out of 3203 individuals, 19% reported falls and 10%
      falls with injury 4 years after the baseline examination; participants with falls
      were more likely to be >or=60 years of age, be female, report lower income, have
      >2 comorbidities, report alcohol use, report wearing bifocal glasses, and report
      obesity. Among those who reported falls, 7% had CVI (visual acuity >20/40)
      compared with 4% who did not report falls; and 49% had PVI (mean deviation < -2
      dB) compared with 39% of those who did not report falls (both P<0.0001). After
      adjusting for confounders, moderate to severe CVI and PVI were associated with
      increased risk for falls (odds ratio [OR], 2.36; 95% confidence interval [CI],
      1.02-5.45; P(trend) = 0.04; and OR, 1.42; 95% CI, 1.06-1.91l P(trend) = 0.01,
      respectively) and with falls with injury (OR, 2.76; 95% CI, 1.10-7.02; P(value) =
      0.03; and OR, 1.40; 95% CI, 0.94-2.05 P(trend) = 0.04, respectively).
      CONCLUSIONS: Both CVI and PVI were independently associated with increased risk
      for falls and falls with injury 4 years after the initial examination in a dose
      response manner. Although vision-related interventions for preventing falls have
      mainly focused on correcting CVI, this study suggests that targeting both central
      and peripheral components may be necessary to effectively reduce rates of falls
      and falls with injury related to vision loss.

PMID- 20031227
TI  - Distribution of axial length and ocular biometry measured using partial coherence
      laser interferometry (IOL Master) in an older white population.
AB  - PURPOSE: We aimed to describe norms for the distribution of axial length (AL) and
      other ocular biometric parameters in an older Caucasian population, measured
      using partial coherence laser interferometry (Zeiss IOL Master; Carl Zeiss AG,
      Oberkochen, Germany), a technique now routinely used in measuring AL before
      cataract surgery. We also aimed to assess age and gender relationships with these
      parameters and their correlations with spherical equivalent refraction (SER).
      DESIGN: Cross-sectional analysis of the Blue Mountains Eye Study (BMES) cohort at
      the examinations (10-year follow-up examination). PARTICIPANTS: From 2002 to
      2004, 1952 persons (76% of surviving baseline BMES participants) aged 59 years or
      older had ocular biometry measured at the 10-year examinations. METHODS:
      Spherical equivalent refraction was calculated as the sum of sphere +0.5 cylinder
      power, after protocol refraction. Measurements of AL, corneal curvature (K1),
      anterior chamber depth (ACD), and corneal diameter (WTW) were performed using the
      IOL Master. Only right phakic eyes (n = 1335) with biometry data were included.
      MAIN OUTCOME MEASURES: Axial length distribution. RESULTS: Mean AL was 23.44 mm
      (95% confidence interval [CI], 23.38-23.50) and was greater in men, 23.76 mm (CI,
      23.68-23.84), than in women, 23.19 mm (CI, 23.11-23.27). The mean K1, ACD, and
      WTW were 43.42 diopters (D), 3.10 mm, and 12.06 mm, respectively. The AL and ACD
      distributions were both positively skewed and peaked, whereas the WTW and K1
      distributions were near normal. From age 59 years or older, a mean reduction in
      AL with age was observed (P for trend = 0.005), 0.12 mm per decade (P = 0.0176)
      in women but only 0.02 mm per decade (P = 0.6319) in men. Mean SER was 0.58 D,
      and the distribution was peaked with a negative skew. The SER was negatively
      correlated with both AL (beta coefficient -0.688) and ACD (beta coefficient 
      0.222), but not with K1 or WTW. CONCLUSIONS: These data provide normative values
      in the older general population for AL measured using the IOL Master. Axial
      length distribution was peaked and skewed, suggesting an active modulation
      process.

PMID- 20031228
TI  - Natural history of Leber's hereditary optic neuropathy: longitudinal analysis of
      the retinal nerve fiber layer by optical coherence tomography.
AB  - PURPOSE: To investigate by optical coherence tomography (OCT) the topographic
      pattern and temporal sequence of fiber loss in the peripapillary retinal nerve
      fiber layer (RNFL) of patients with Leber's hereditary optic neuropathy (LHON) in
      a longitudinal follow-up. DESIGN: Cohort study. PARTICIPANTS: Six eyes of 4
      patients with molecularly defined LHON were enrolled before the subacute period
      of visual loss. METHODS: Subjects were studied by StratusOCT (Carl Zeiss Meditec,
      Inc., Dublin, CA) during a 9-month follow-up starting from the presymptomatic
      stage of the disease. Examinations were carried out at 4 different time points:
      presymptomatic stage, time of visual loss, and 3 and 9 months later. MAIN OUTCOME
      MEASURES: Peripapillary RNFL thickness for each quadrant of the optic nerve.
      Statistical comparisons were performed by ordinary analysis of variance with
      Dunnett's post-test. RESULTS: A significant increase of RNFL thickness was
      detected in the temporal and inferior quadrants between the presymptomatic stage
      and the disease onset (P<0.05). The 360-degree average and the superior and nasal
      quadrants showed a nonstatistically significant increase of thickness at this
      time. In the 360-degree average (P<0.01), superior (P<0.01), nasal (P<0.05), and
      inferior (P<0.01) quadrants, RNFL thickening showed statistically significant
      changes between the presymptomatic stage and the 3-month follow-up. At 3 months,
      a nonsignificant reduction of RNFL thickness was detected in the temporal
      quadrant. A significant reduction of RNFL was detected in all but the nasal
      quadrants between the presymptomatic stage and the 9-month Follow-up.
      CONCLUSIONS: The RNFL thickness increase first appeared at the temporal and
      inferior quadrants. Conversely, at 3 months the thickening fibers were more
      evident in the superior and nasal quadrants. These findings are consistent with
      the established preferential early involvement of the papillomacular bundle in
      LHON. We also demonstrated the previously unrecognized simultaneous early
      involvement of the inferior quadrant. The late involvement of both superior and
      nasal quadrants suggests a dynamic evolution of the acute stage that continues
      for 3 months and may represent a therapeutic window of opportunity.

PMID- 20031229
TI  - Severe intraocular inflammation after intravitreal injection of bevacizumab.
AB  - PURPOSE: To report 5 cases of severe intraocular inflammation that developed
      after an intravitreal injection of the same lot of bevacizumab. DESIGN:
      Retrospective case series. PARTICIPANTS: Patients treated with an intravitreal
      injection of bevacizumab (lot B3003B01). METHODS: The clinical charts of 35 eyes
      of 35 consecutive patients who were treated with intravitreal injection of lot
      B3003B01 bevacizumab from December 18, 2008, through January 20, 2009, were
      reviewed. MAIN OUTCOME MEASURES: Incidence of intraocular inflammation, results
      of bacterial cultures, best-corrected visual acuity (BCVA), and endothelial cell
      density. RESULTS: Five (14.3%) of the 35 cases had severe intraocular
      inflammation, and the inflammation had some characteristics of toxic anterior
      segment syndrome (TASS). Five of the 5 cases had a predominantly anterior chamber
      reaction, and 4 of the 5 cases were accompanied by hypopyon. Undiluted samples
      collected from both the aqueous and vitreous of the 5 cases were culture
      negative. The BCVA was 0.66+/-0.29 (mean+/-standard deviations) logarithm of the
      minimum angle resolution (logMAR) units, and the endothelial cell density was
      2683.6+/-97.3/mm(2) before the intravitreal bevacizumab. At the final visit, the
      BCVA was 0.44+/-0.36 logMAR units, and the cell density was 2679.0+/-217.5/mm(2).
      These differences were not significant (P = 0.171 and 0.964). CONCLUSIONS: These
      observations indicate that an intravitreal injection of bevacizumab can induce
      sterile endophthalmitis that has characteristics of TASS.

PMID- 20031231
TI  - Screening for glaucoma in high-risk populations using optical coherence
      tomography.
AB  - OBJECTIVE: To estimate the diagnostic accuracy of Stratus optical coherence
      tomography (OCT) for glaucoma screening in high-risk populations. DESIGN: Cross
      sectional evaluation of a diagnostic test for screening. PARTICIPANTS: Three
      hundred thirty-three community-based volunteer participants with risk factors for
      glaucoma. METHODS: The optic nerve and peripapillary retinal nerve fiber layer
      (RNFL) of participants' eyes were scanned using the Stratus OCT. Based on an
      ophthalmologic examination and frequency doubling perimetry, eyes were classified
      into 4 categories: normal, possible glaucoma, probable glaucoma, and definitive
      glaucoma. MAIN OUTCOME MEASURES: The sensitivities, specificities, positive and
      negative likelihood ratios of the RNFL, optic disc parameters, and their
      combinations were calculated. RESULTS: The right eyes were retained for analyses.
      After excluding eyes with missing data or with poor quality scans, the data of
      210 right eyes were analyzed. Six eyes had definitive glaucoma. Combining the
      best performing optic nerve head parameters (cup diameter or cup/disc vertical
      ratio or cup/disc area ratio) and RNFL parameters (superior average or inferior
      average or overall average) using AND-logic resulted in a sensitivity of 67% (95%
      confidence interval [CI], 24%-94%), specificity of 96% (95% CI, 92%-98%), a
      positive likelihood ratio of 17.08 (95% CI, 7.06-41.4), and a negative likelihood
      ratio of 0.35 (95% CI, 0.11-1.08). CONCLUSIONS: When adequate quality scans may
      be obtained, the Stratus has moderate sensitivity and high specificity for
      definitive glaucoma. Specificity is increased when parameters from both the optic
      nerve head and RNFL scans are combined.

PMID- 20031230
TI  - Descemet's stripping automated endothelial keratoplasty outcomes compared with
      penetrating keratoplasty from the Cornea Donor Study.
AB  - PURPOSE: To assess outcomes 1 year after Descemet's stripping automated
      endothelial keratoplasty (DSAEK) in comparison with penetrating keratoplasty
      (PKP) from the Specular Microscopy Ancillary Study (SMAS) of the Cornea Donor
      Study. DESIGN: Multicenter, prospective, nonrandomized clinical trial.
      PARTICIPANTS: A total of 173 subjects undergoing DSAEK for a moderate risk
      condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema)
      compared with 410 subjects undergoing PKP from the SMAS who had clear grafts with
      at least 1 postoperative specular image within a 15-month follow-up period.
      METHODS: The DSAEK procedures were performed by 2 experienced surgeons per their
      individual techniques, using the same donor and similar recipient criteria as for
      the PKP procedures in the SMAS performed by 68 surgeons at 45 sites, with donors
      provided from 31 eye banks. Graft success and complications for the DSAEK group
      were assessed and compared with the SMAS group. Endothelial cell density (ECD)
      was determined from baseline donor, 6-month (range, 5-7 months), and 12-month
      (range, 9-15 months) postoperative central endothelial images by the same reading
      center used in the SMAS. MAIN OUTCOME MEASURES: Endothelial cell density and
      graft survival at 1 year. RESULTS: Although the DSAEK recipient group criteria
      were similar to the PKP group, Fuchs' dystrophy was more prevalent in the DSAEK
      group (85% vs. 64%) and pseudophakic corneal edema was less prevalent (13% vs.
      32%, P<0.001). The regraft rate within 15 months was 2.3% (DSAEK group) and 1.3%
      (PKP group) (P = 0.50). Percent endothelial cell loss was 34+/-22% versus 11+/
      20% (6 months) and 38+/-22% versus 20+/-23% (12 months) in the DSAEK and PKP
      groups, respectively (both P<0.001). Preoperative diagnosis affected endothelial
      cell loss over time; in the PKP group, the subjects with pseudophakic/aphakic
      corneal edema experienced significantly higher 12-month cell loss than the
      subjects with Fuchs' dystrophy (28% vs. 16%, P = 0.01), whereas in the DSAEK
      group, the 12-month cell loss was comparable for the 2 diagnoses (41% vs. 37%, P
      = 0.59). CONCLUSIONS: One year post-transplantation, overall graft success was
      comparable for DSAEK and PKP procedures and endothelial cell loss was higher with
      DSAEK.

PMID- 20031232
TI  - Infant object categorization transcends diverse object-context relations.
AB  - Infants' categorization of objects in different object-context relations was
      investigated. The experiment used a multiple-exemplar habituation-categorization
      procedure where 92 6-month olds formed categories of animals and vehicles
      embedded in congruent, incongruent, and homogeneous object-context relations.
      Across diverse object-context relations, infants habituated to multiple exemplars
      within a category and categorized novel members of both animal and vehicle
      categories. Infants showed a slight advantage for categorizing animals. Infant
      object categorization appears to be robust to diversity in object-context
      relations.

PMID- 20031233
TI  - Infants use attention but not emotions to predict others' actions.
AB  - Phillips et al. (2002) suggest that by 12-14 months, infants can use a person's
      emotional and attentional cues to predict that person's actions. However, this
      work was conducted using only positive emotions, which is problematic because
      attention and positive emotions lead to the same prediction about a person's
      actions, thus leaving unclear whether infants made predictions based upon
      attention and emotion or attention alone. To get around this problem, we used
      both positive and negative emotions in a looking-time paradigm to investigate
      whether 14-month-old infants can use emotional cues to predict a person's
      actions. The findings suggest that infants used attentional but not emotional
      cues as predictors. We argue that while 14-month-olds can use another person's
      emotion cues to modify their own behavior (as in social referencing situations),
      they do not yet use them robustly to predict the other's behavior.

PMID- 20031235
TI  - Serotonin transporter polymorphisms and early response to antipsychotic treatment
      in first episode of psychosis.
AB  - There is substantial evidence suggesting that individual variability in
      antipsychotic treatment response could be genetically determined. Variations in
      several serotonin transporter (5-HTT) gene polymorphisms have been associated
      with antipsychotic response among chronic patients with schizophrenia, although
      their implication in early response among first-episode patients remains unclear.
      Two polymorphisms in the 5-HTT gene (a 44 bp insertion/deletion in the promoter
      region and the functional polymorphism rs25531) were genotyped in a sample of 147
      drug-naive patients experiencing a first episode of a non-affective psychosis.
      Early (6 weeks) response to antipsychotic treatment with haloperidol, olanzapine
      or risperidone was assessed with the Brief Psychiatric Rating Scale, the Scale
      for the Assessment of Positive Symptoms, and the Scale for the Assessment of
      Negative Symptoms. No clear association was found between the rs25531 variant and
      treatment response. However, significant associations were observed between 5-HTT
      LPR variants and early negative symptom response among first-episode patients
      with psychosis. Our results suggest a minor contribution to antipsychotic drug
      response of genetic alterations in the 5-HTT gene.

PMID- 20031234
TI  - The prevalence of night eating syndrome and binge eating disorder among
      overweight and obese individuals with serious mental illness.
AB  - The prevalence of night eating syndrome (NES) and binge eating disorder (BED) was
      assessed among overweight and obese, weight-loss-seeking individuals with serious
      mental illness (SMI). Sixty-eight consecutive overweight (BMI > or = 25 kg/m(2))
      and obese (BMI > or = 30 kg/m(2)) individuals with SMI (mean age = 43.9 years;
      mean BMI = 37.2 kg/(2); 67.6% Caucasian, 60.3% female) who were enrolled in a
      group behavioral weight loss treatment program were assessed at baseline for NES
      and BED with clinician-administered diagnostic interviews. Using conservative
      criteria, 25.0% met criteria for NES, 5.9% met criteria for BED, and only one
      participant met criteria for both NES and BED. This is the first study to find
      that obese individuals with SMI, compared with previously studied populations,
      are at significantly greater risk for NES, but are not at greater risk for BED.
      Stress, sleep, and medication use might account for the high prevalence of NES
      found in this population.

PMID- 20031236
TI  - Chemical destruction of brain noradrenergic neurons affects splenic cytokine
      production.
AB  - The neurotransmitter noradrenaline (NA) plays a pivotal role in immune
      regulation. Here we used the selective neurotoxin N-(2-chloroethyl)-N-ethyl-2
      bromobenzylamine (DSP-4) to investigate the impact of central NA depletion on
      cytokine production by splenic monocytes/macrophages and T cells. Intraperitoneal
      administration of DSP-4 in adult rats induced a substantial reduction of
      noradrenergic neurons in the locus coeruleus and the A5 cell group. The
      degeneration of brainstem noradrenergic neurons was accompanied by a significant
      decrease in the production of interleukin (IL)-1beta, IL-6, and tumor necrosis
      factor (TNF)-alpha by lipopolysaccharide-stimulated splenocytes. In addition,
      upon T cell receptor stimulation with anti-CD3, isolated splenocytes of DSP-4
      treated animals produced significantly less interferon (IFN)-gamma but not IL-2
      and IL-4. The proportion of monocytes/macrophages and T cells in the spleen
      remained unaffected by the neurotoxin treatment, however, the percentage of
      natural killer cells decreased significantly. The findings suggest that a certain
      level of central noradrenergic tone is required for normal functioning of
      peripheral immune cells.

PMID- 20031237
TI  - Biomarker candidate discovery in Atlantic cod (Gadus morhua) continuously exposed
      to North Sea produced water from egg to fry.
AB  - In this study Atlantic cod (Gadus morhua) were exposed to different levels of
      North Sea produced water (PW) and 17beta-oestradiol (E(2)), a natural oestrogen,
      from egg to fry stage (90 days). By comparing changes in protein expression
      following E(2) exposure to changes induced by PW treatment, we were able to
      compare the induced changes by PW to the mode of action of oestrogens. Changes in
      the proteome in response to exposure in whole cod fry (approximately 80 days post
      hatching, dph) were detected by two-dimensional gel electrophoresis and image
      analysis and identified by MALDI-ToF-ToF mass spectrometry, using a newly
      developed cod EST database and the NCBI database. Many of the protein changes
      occurred at low levels (0.01% and 0.1% PW) of exposure, indicating putative
      biological responses at lower levels than previously detected. Using discriminant
      analysis, we identified a set of protein changes that may be useful as biomarker
      candidates of produced water (PW) and oestradiol exposure in Atlantic cod fry.
      The biomarker candidates discovered in this study may, following validation,
      prove effective as diagnostic tools in monitoring exposure and effects of
      discharges from the petroleum industry offshore, aiding future environmental risk
      analysis and risk management.

PMID- 20031238
TI  - Prevalence of pain in elderly hospitalized patients.
AB  - Several studies indicate that pain, although very common in the elderly, is under
      treated, because it is considered as a concomitant effect of aging. This study
      aimed to evaluate the prevalence of pain among patients in eight Italian
      geriatric hospital departments, correlated to prescribed therapy. We enrolled 387
      patients in the study, 367 of whom were evaluated. Each patient's recovery, co
      morbidity, pain intensity, prescribed therapy, side effects, duration of pain,
      and efficacy of therapy were monitored during two 15-day periods from 15 July to
      end of August 2008, and from 1 October to 15 November 2008. The results of this
      study confirmed that hypertension, cardiopathic disease, diabetes, and chronic
      obstructive pulmonary disease (COPD) are common pathologies, and that pain is
      present in 67.3% of those recovered in geriatric departments. In general,
      however, pain is not treated. Indeed only 49% of those with pain had any type of
      treatment, which was adequate for the pain intensity. In fact 74.5% of patients
      considered the therapy to be of low or no efficacy. These data demonstrate the
      presence of pain in a high percentage of elderly patients, which is either not
      treated, or treated inadequately. Controlling pain is essential in elderly
      patients in order to allow a normal life and an active role in family and
      society. The main conclusion is that pain is often poorly considered in the
      elderly, thus leading to a dangerous under-treatment. We want to underline the
      crucial clinical impact of such under-treatment in elderly patients.

PMID- 20031239
TI  - Interventions to reduce verocytotoxigenic Escherichia coli in ground beef in
      Argentina: a simulation study.
AB  - A stochastic simulation model was used to assess the effects of measures
      implemented in the agri-food-chain to reduce the contamination of ground beef
      with verotoxigenic Escherichia coli (VTEC). A published risk assessment model
      developed in Argentina was used as baseline scenario. Control measures assessed
      were based on either a reduction in herd prevalence of infection due to
      vaccination, reduction in opportunity for cross-contamination in the
      slaughterhouses by the introduction of an on-line hide-wash cabinet, and control
      of storage temperature in slaughterhouses, retail and home. Additionally, the
      increase of feedlot production was modelled. Simulations suggested that the
      greatest potential impact was associated with hide-wash cabinet and vaccination,
      measures aimed to reduce the VTEC prevalence and concentration in the cattle
      hides at the beginning of the food-chain. Control of storage temperature was not
      effective if the carcasses cross-contamination with the pathogen was not
      prevented or reduced. An increase production (fattening) of cattle in feedlots
      may raise the risk of VTEC infection and its sequelae. This information can be
      used as a basis for measures of risk management.

PMID- 20031240
TI  - Determination of the within and between flock prevalence and identification of
      risk factors for Salmonella infections in laying hen flocks housed in
      conventional and alternative systems.
AB  - Salmonella outbreaks in humans are often linked with the consumption of
      contaminated eggs. Therefore a profound knowledge of the actual prevalence of
      Salmonella spp. in laying hens and the factors that influence the presence and
      persistence of Salmonella on a farm is of utmost importance. The housing of
      laying hens in conventional battery cages will be forbidden in the European Union
      (EU) from 2012 onwards. There is an urgent need to evaluate whether this move to
      alternative housing systems will influence the prevalence of Salmonella in laying
      hens. Therefore, a cross-sectional study was performed in 5 European countries
      (Belgium, Germany, Greece, Italy and Switzerland) to determine the between and
      within flock prevalence of hens shedding Salmonella and to investigate whether
      there is an effect of the housing type on Salmonella prevalence. In total 292
      laying hen farms were sampled in the month prior to depopulation. An on-farm
      questionnaire was used to collect information on general management practices and
      specific characteristics of the sampled flock. Twenty-nine flocks were found
      positive for at least 1 Salmonella-serotype. In these flocks the within flock
      prevalence of shedding hens, determined by individual sampling of 40 hens, varied
      between 0% and 27.50%. A wide variety of serotypes was isolated with Salmonella
      Enteritidis as the most common. Housing in conventional battery cages, the
      absence of dry cleaning in between production rounds and sampling in winter
      turned out to be risk factors for the shedding of Salmonella Enteritidis or
      Typhimurium (P<0.05).

PMID- 20031242
TI  - Visual strategies of sub-elite cricket batsmen in response to different ball
      velocities.
AB  - When different interceptive skills are considered, humans tend not to pursuit
      track the approaching object along its entire trajectory to the point of
      interception. Previous research of cricket batsmen facing medium paced deliveries
      reported pursuit visual tracking of the ball for the first 100-150 ms of flight
      followed by a saccade to the predicted ball bounce location. The aim of this
      study was to examine eye movements of batsmen while facing a range of slow to
      medium pace delivery speeds. Thirteen sub-elite batsmen faced 36 deliveries from
      a ball machine in which the projection speed was randomly varied across a range
      of 17-25 ms(-1). The foveal gaze of the batsmen was recorded with a monocular eye
      movement registration system. Gaze strategies differed between participants in
      several ways, i.e., in the initial location of gaze prior to delivery (on the
      outlet of the ball machine or "parked" at a location on the predicted flight
      trajectory), the behavior immediately after ball release (pursuit tracking or
      saccade), and the behavior in mid-late flight (predictive saccade to the bounce
      point or "parafoveal" pursuit tracking). Across the range of delivery speeds used
      in the current study, it was possible to pursuit track the ball from release to
      bounce point but it was also possible to choose to make saccades along the
      trajectory. Depending on the spatio-temporal demands of the task and the
      intentions of the batsman a range of visual search strategies can be employed to
      support their actions.

PMID- 20031241
TI  - Progress and compliance in alcohol abuse treatment.
AB  - Improving patient compliance with physicians' treatment or prescription
      recommendations is an important goal in medical practice. We examine the
      relationship between treatment progress and patient compliance. We hypothesize
      that patients balance expected benefits and costs during a treatment episode when
      deciding on compliance; a patient is more likely to comply if doing so results in
      an expected gain in health benefit. We use a unique data set of outpatient
      alcohol abuse treatment to identify a relationship between treatment progress and
      compliance. Treatment progress is measured by the clinician's comments after each
      attended visit. Compliance is measured by a client attending a scheduled
      appointment, and continuing with treatment. We find that a patient who is making
      progress is less likely to drop out of treatment. We find no evidence that
      treatment progress raises the likelihood of a patient attending the next
      scheduled visit. Our results are robust to unobserved patient heterogeneity.

PMID- 20031243
TI  - Prevalence of broad-spectrum cephalosporin-resistant Escherichia coli isolates in
      food samples in Tunisia, and characterization of integrons and antimicrobial
      resistance mechanisms implicated.
AB  - The presence of broad-spectrum-cephalosporin-resistant Escherichia coli isolates
      and the implicated mechanisms of resistance were investigated in 79 food samples
      of animal origin obtained in different supermarkets and local butcheries in
      Tunisia. Ten of these samples (12.6%) harbored extended-spectrum beta-lactamase
      (ESBL) producing E. coli isolates and 13 ESBL-positive isolates were recovered
      (one or two/sample), which exhibited nine different Pulsed-Field-Gel
      Electrophoresis (PFGE) patterns. ESBLs detected were the following: CTX-M-1 (10
      strains), CTX-M-1+TEM-1b (2 strains) and CTX-M-1+TEM-20 (1 strain). The orf477
      sequence was identified downstream of bla(CTX-M-1) gene in all 13 strains and
      ISEcp1 upstream in 9 strains. All ESBL-positive strains were included into
      phylogenetic group A or B1 (4 and 9 strains, respectively). Three of the 79 food
      samples (3.8%) contained broad-spectrum-cephalosporin-resistant and ESBL-negative
      E. coli isolates with AmpC phenotype. One isolate per sample was studied, and
      they showed unrelated PFGE patterns. The CMY-2 type beta-lactamase was identified
      in one of these 3 strains and specific point mutations in the promoter/attenuator
      region of ampC gene (at positions -42, -18, -1 and +58) were detected in the
      remaining two strains. Twelve ESBL-positive and one ESBL-negative E. coli strains
      contained class 1 integrons with the following gene cassette arrangements:
      dfrA1+aadA (6 strains) and dfrA17+aadA5 (7 strains). E. coli strains from food
      samples could represent a reservoir of ESBL-encoding genes and integrons that
      could be transmitted to humans through the food chain.

PMID- 20031244
TI  - Microsatellite loci to recognize species for the cheese starter and contaminating
      strains associated with cheese manufacturing.
AB  - We report the development of 17 microsatellite markers in the cheese fungi
      Penicillium camemberti and P. roqueforti, using an enrichment protocol.
      Polymorphism and cross-amplification were explored using 23 isolates of P.
      camemberti, 26 isolates of P. roqueforti, and 2 isolates of each of the P.
      chrysogenum and P. nalgiovense species, used to produce meat fermented products.
      The markers appeared useful for differentiating species, both using their
      amplification sizes and the sequences of their flanking regions. The
      microsatellite locus PC4 was particularly suitable for distinguishing contaminant
      species closely related to P. camemberti and for clarifying the phylogenetic
      relationship of this species with its supposed ancestral form, P. commune. We
      analyzed 22 isolates from different culture collections assigned to the
      morphospecies P. commune, most of them occurring as food spoilers, mainly from
      the cheese environment. None of them exhibited identical sequences with the ex
      type isolate of the species P. commune. They were instead distributed into two
      other distinct lineages, corresponding to the old species P. fuscoglaucum and P.
      biforme, previously synonymized respectively with P. commune and P. camemberti.
      The ex-type isolate of P. commune was strictly identical to P. camemberti at all
      the loci examined. P. caseifulvum, a non toxinogenic species described as a new
      candidate for cheese fermentation, also exhibited sequences identical to P.
      camemberti. The microsatellite locus PC4 may therefore be considered as a useful
      candidate for the barcode of these economically important species.

PMID- 20031245
TI  - Plasma sRAGE is independently associated with high sensitivity C-reactive protein
      in type 2 diabetes without coronary artery disease.
AB  - Our studies suggest that plasma soluble advanced glycation end products (sRAGEs)
      has significantly negative association with high sensitivity C-reactive protein
      (hs-CRP) in 245 type 2 diabetes patients without diagnosed coronary artery
      disease (CAD). sRAGE maybe act as a novel biomarker for predicting the
      atherosclerosis in diabetes at the early stage.

PMID- 20031246
TI  - Proteomic analysis reveals a major role for contact inhibition in the terminal
      differentiation of hepatocytes.
AB  - BACKGROUND & AIMS: Hepatocytes are considered an exception of the paradigmatic
      inverse correlation between cell proliferation and terminal differentiation. In
      fact, hepatic vital functions are guaranteed by proliferating parenchymal cells
      during liver regeneration. However, a fine molecular characterization of the
      relationship between proliferation and differentiation in hepatocytes has been
      hampered by the lack of reliable in vivo or in vitro models. METHODS: The
      hepatocyte terminal differentiation program was characterized in the
      immortalized, untransformed and differentiated hepatocytic cell line MMH, using
      several techniques. Particularly, two-dimensional difference gel electrophoresis
      combined to tandem mass spectrometry proteomic approach was used. Cell cycle and
      cell adhesion properties of MMH have been altered using either myc-overexpression
      and MEK1/2 inhibition or a constitutive active beta-catenin mutant, respectively.
      RESULTS: The hepatocyte terminal differentiation program is stimulated by the
      exit from the cell cycle induced by cell-cell contact. Comparative proteomic
      analysis of proliferating versus quiescent hepatocytes validated the importance
      of contact inhibition, identifying 68 differently expressed gene products,
      representing 49 unique proteins. Notably, enzymes involved in important liver
      functions such as detoxification processes, lipid metabolism, iron and vitamin A
      storage and secretion, anti-inflammatory response and exocytosis were found
      significantly up-regulated in quiescent hepatocytes. Finally, we found that: (i)
      cell cycle arrest induced by MEK1/2 inhibition is not sufficient to induce
      hepatic product expression; (ii) constitutive activation of beta-catenin
      counteracts the contact inhibition-induced terminal differentiation. CONCLUSION:
      The hepatocyte terminal differentiation program requires a quiescent state
      maintained by cell-cell contact through the E-cadherin/beta-catenin pathway,
      rather than the inhibition of proliferation.

PMID- 20031247
TI  - Adult-onset ornithine transcarbamylase (OTC) deficiency unmasked by the Atkins'
      diet.
AB  - BACKGROUND & AIMS: Late-onset symptoms of urea-cycle disorder may lead to a life
      threatening disease which is often undetected. We report the clinical and
      metabolic manifestations of acute hyperammonemic encephalopathy in a 47-year-old
      asymptomatic man with ornithine transcarbamylase (OTC) deficiency. The
      hyperammonemic encephalopathy was unmasked by a high-protein Atkins diet.
      METHODS: Genetic analysis of the patient's family, 89 unrelated Ashkenazi Jewish
      and 50 unrelated Europeans subjects was performed using polymerase chain reaction
      amplification and DNA sequencing of the OTC gene. RESULTS: Treatment with
      hemodialysis, provision of adequate calories to prevent catabolism, and protein
      elimination for 24h followed by protein restriction and ammonia scavenging
      medications effectively lowered the patient's plasma ammonia level and resulted
      in full recovery. Genetic analysis of the OTC gene revealed a novel hemizygous
      missense mutation in exon 5 (c.477T>G), leading to an isoleucine-to-methionine
      substitution in codon 159 (Ile159Met). Further genetic analysis of the patient's
      family yielded the mutation in many of them, although findings were negative in
      89 unrelated Ashkenazi Jewish and 50 unrelated Europeans subjects. CONCLUSIONS:
      This is the first reported case of an adult urea-cycle defect unmasked by the
      Atkins diet. Measurements of serum ammonia level must be part of the basic work
      up in all patients presenting with encephalopathy of unknown origin even in the
      absence of liver dysfunction. Awareness of this important association can
      contribute to prompt diagnosis and life-saving treatment. Correct diagnosis is
      also important to prevent future recurrences and to provide genetic counselling
      for family members.

PMID- 20031249
TI  - Purchasing health services abroad: practices of cross-border contracting and
      patient mobility in six European countries.
AB  - OBJECTIVES: Contracting health services outside the public, statutory health
      system entails purchasing capacity from domestic non-public providers or from
      providers abroad. Over the last decade, these practices have made their way into
      European health systems, brought about by performance-oriented reforms and EU
      principles of free movement. The aim of the article is to explain the
      development, functioning, purposes and possible implications of cross-border
      contracting. METHODS: Primary and secondary sources on purchasing from providers
      abroad have been collected in a systematic way and analysed in a structured
      frame. RESULTS: We found practices in six European countries. The findings
      suggest that purchasers from benefit-in-kind systems contract capacity abroad
      when this responds to unmet demand; pressures domestic providers; and/or offers
      financial advantages, especially where statutory purchasers compete. Providers
      which receive patients tend to be located in countries where treatment costs are
      lower and/or where providers compete. The modalities of purchasing and delivering
      care abroad vary considerably depending on contracts being centralised or direct,
      the involvement of middlemen, funding and pricing mechanisms, cross-border
      pathways and volumes of patient flows. CONCLUSIONS: The arrangements and concepts
      which cross-border contracting relies on suggest that statutory health
      purchasers, under pressure to deliver value for money and striving for cost
      efficiency, experiment with new ways of organising health services for their
      populations.

PMID- 20031248
TI  - Minor access control of Hong Kong under the Framework Convention on Tobacco
      Control.
AB  - BACKGROUND: Asia's tobacco control movement was strengthened owing to the need to
      fulfill the Framework Convention on Tobacco Control (FCTC). OBJECTIVE: The
      present study aims to assess the compliance rates of tobacco retailers to the law
      forbidding the sales of tobacco to minors in Hong Kong before and after the
      growth of the tobacco control movement brought by the enactment of the newly
      amended tobacco control law with effect from 2007. The legislation was enacted to
      fulfill the FCTC. DESIGN AND METHOD: Two waves of territory-wide compliance
      checks conducted in 2006 and 2008 were compared. The compliance check was
      conducted using Standard Protocol. RESULT: The overall compliance rate was still
      low though it increased from 18.9% in 2006 to 27.0% in 2008. The compliance rate
      of convenience stores and newspaper stands improved whereas the rate for
      restaurants, grocery stores and petrol stations worsened. Less tobacco retailing
      outlets displayed a specified warning sign required in 2008 (33.7%) comparing to
      2006 (41.4%). CONCLUSION: The indoor smoking ban of the FCTC unintentionally
      changed the cigarette retailing landscape and finally improved the compliance
      rate. The case study also demonstrated that the Asia region still has much room
      for improvement in fulfilling the FCTC in term of effective implementation and
      enforcement.

PMID- 20031250
TI  - Measurement of efficiency of the dialysis sector in Turkey using data envelopment
      analysis.
AB  - OBJECTIVES: Limited prior work exists on the efficiency of the dialysis sector
      characterized by steady increase in the dialysis population, providers, and
      dialysis expenditures in Turkey. The study aimed to examine technical efficiency
      among producers of dialysis treatment in Turkey. METHODS: Cross-sectional data
      were used from the 2008 Turkish Statistical Yearbook of Dialysis for total 830
      dialysis facilities. Efficiency was measured using data envelopment analysis
      technique. RESULTS: Results drawn from an input-oriented variable-returns-to
      scale model showed technical efficiency from only 3% of facilities, as well as
      50% reduction in inputs. Mean efficiency score was found higher among facilities
      that were freestanding, private, affiliated with international chains, older, and
      located in Istanbul. CONCLUSION: Efficiency enhancement in dialysis production in
      Turkey should be placed on the priority agenda, along with careful evaluation of
      impact of the already-inserted changes on efficiency.

PMID- 20031251
TI  - Can an appropriateness evaluation tool be used to prioritize patients on a
      waiting list for cataract extraction?
AB  - OBJECTIVES: To determine whether a system originally developed to ascertain the
      appropriateness of cataract intervention may also be used to prioritize patients
      on cataract extraction waiting lists. METHODS: The IRYSS-appropriateness of
      indication for cataract surgery tool and the IRYSS-Cataract Priority Score were
      applied to a sample of 5448 patients consecutively placed on waiting lists for
      cataract surgery. Clinical data were gathered by ophthalmologists, and patients
      self-completed the Visual Function Index-14. The general linear model (GLM) was
      used to assign scores to the categories of the appropriateness and priority
      criteria. The relationship between both systems was evaluated by correlating
      scores. To assess the validity of the new appropriateness and priority scores,
      correlations with visual acuity (VA) and visual function were calculated.
      RESULTS: The GLM method generated highly similar scores for both appropriateness
      and prioritization systems. The correlation between scores was very strong
      (r=0.96). The appropriateness scoring system correlated 0.29 with VA and 0.21
      with gain in visual function. The priority system correlated -0.54 with VA and 
      0.28 with preintervention visual function. CONCLUSIONS: The new appropriateness
      scoring system strongly correlates with the priority scoring system. This easy-to
      use appropriateness rating could serve as a tool for simultaneously assessing the
      appropriateness of cataract surgery and assigning priority.

PMID- 20031252
TI  - Cell-cell communication in Arabidopsis early embryogenesis.
AB  - The basic body plan of the adult plant is established during embryogenesis,
      resulting in the juvenile form of the seedling. Arabidopsis embryogenesis is
      distinguished by a highly regular pattern of cell divisions. Some of these
      divisions are asymmetric, generating daughter cells with different fates.
      However, their subsequent differentiation might still depend on cell-cell
      communication to be fully accomplished or maintained. In some cases, cell fate
      specification solely depends on cell-cell communication that in general plays an
      important role in the generation of positional information within the embryo.
      Although auxin-dependent signalling has received much attention, other ways of
      cell-cell communication have also been demonstrated or suggested. This review
      focuses on aspects of pattern formation and cell-cell communication during
      Arabidopsis embryogenesis up to the mid-globular stage of development.

PMID- 20031253
TI  - Small RNAs in flower development.
AB  - Development of multi-cellular organisms depends on the correct spatial and
      temporal expression of numerous genes acting in concert to form regulatory
      networks. The expression of individual genes can be controlled at different
      levels, e.g. at the transcriptional level by sequence-specific binding of
      transcription factors and/or by epigenetic modifications, or at the post
      transcriptional level, e.g., by modulating translation or protein stability.
      Within the last decade the picture of gene regulatory mechanisms has been
      substantially enriched by the identification of small RNAs (sRNAs) of several
      distinct subspecies. Non-coding regulatory sRNAs contribute to transcriptional
      and post-transcriptional gene regulation by different modes of sequence-specific
      interaction with their targets. MicroRNAs (miRNAs), which guide post
      transcriptional gene silencing, have been found to contribute to a variety of
      developmental programs in plants and animals. Here we provide an overview about
      generation and action of miRNAs and other small RNAs, and their contribution to
      an important developmental process in plants, flower formation.

PMID- 20031254
TI  - Exogenously applied isothiocyanates enhance glutathione S-transferase expression
      in Arabidopsis but act as herbicides at higher concentrations.
AB  - Isothiocyanates (ITCs) are sulfur-containing compounds that are generated by the
      glucosinolate-myrosinase system in plants. Although previous greenhouse studies
      have demonstrated the phytotoxicity of ITCs, their action modes are still
      unknown. In this study, we report the physiological responses of Arabidopsis
      thaliana treated with three exogenous ITCs: methyl ITC, allyl ITC, and phenethyl
      ITC. Administration of a high dose of each ITC inhibited plant growth and induced
      severe bleaching in the rosette leaves. The bleaching was concomitant with the
      elevation of electrolyte leakage and the generation of hydrogen peroxide.
      Although the three ITCs showed bleaching symptoms, phenethyl ITC was the most
      potent. A low dose of phenethyl ITC, at which the ITC did not promote leaf
      bleaching, enhanced the accumulation of transcripts of glutathione S-transferases
      (GSTs) in Arabidopsis. When 16 GST genes were tested, the levels of transcripts
      corresponding to 5 of the GST genes were enhanced in response to the phenethyl
      ITC treatment. In particular, the expression of a Tau class gene (AtGSTU19,
      At1g78380) responded to the phenethyl ITC treatment. Enhancement of the AtGSTU19
      gene expression also occurred in the treatment of both allyl ITC and methyl ITC.
      These results suggest that the administration of ITCs to Arabidopsis at high
      doses has an herbicidal effect by inducing oxidative burst-like responses, but
      that administration at lower doses enhances the expression of specific GST genes
      in Arabidopsis.

PMID- 20031255
TI  - Cadmium has contrasting effects on polyethylene glycol-sensitive and resistant
      cell lines in the Mediterranean halophyte species Atriplex halimus L.
AB  - Beside a direct toxicity, cadmium impact on plants involves both a secondary
      induced water stress and an oxidative stress. Proliferating cell lines of
      Atriplex halimus were selected for their sensitivity or resistance to
      polyethylene glycol (PEG 10,000, 20%) and then exposed to 100 microM CdCl2 in the
      simultaneous presence or absence of PEG 20% or 150 mM NaCl. The PEG resistant
      cell line exhibited a higher growth in the presence of Cd than the sensitive
      line, although Cd acccumulation was higher in the former than in the latter.
      Exogenous PEG induced an increase in Cd concentration in the sensitive but not in
      the resistant cell line while NaCl induced a decrease in Cd accumulation in both
      cell lines. In the presence of Cd alone, the water content (WC) was higher and
      the osmotic potential was lower in PEG-sensitive than in PEG resistant line. The
      presence of PEG in the Cd-containing medium increased the WC and decreased the
      osmotic potential in PEG-resistant line comparatively to Cd stress alone, while
      an inverse trend was observed for the sensitive line. The PEG-resistant cell line
      displayed a higher ability to cope with oxidative stress in relation to an
      increase of endogenous antioxidants (glutathione and ascorbic acid), a high
      constitutive superoxide dismutase (EC 1.15.1.1) activity and an efficient Cd
      induced increase in glutathione reductase (GR) (EC 1.6.4.1) and ascorbate
      peroxidase (APX) (EC 1.11.1.11). Cadmium tolerance in PEG-resistant line is thus
      not related to any strategy of Cd exclusion or osmotic adjustment but to
      tolerance mechanisms allowing the tissue to restrict the deleterious impact of
      accumulated Cd.

PMID- 20031256
TI  - [Central retinal vein occlusion and internal carotid artery hypoplasia: a case
      report].
AB  - INTRODUCTION: Retinal vein occlusion is usually encountered in the elderly and is
      often associated with systemic vascular disease. It is rarer in young subjects
      and requires a serious etiological search to best adapt the treatment.
      OBSERVATION: We report the case of a central retinal vein occlusion (CRVO) in a
      26-year-old patient who had no pathological history, discovered at a sudden
      decline of vision in the right eye, reduced to light perception. Fundus
      examination and retinal angiography showed an edematous CRVO. Radiologic imaging
      revealed a narrowing of the right carotid canal, probably congenital, and a
      reduction in the size of the right common carotid artery and internal carotid
      artery. Progression was favorable without treatment, and visual acuity improved
      to 8/10. CONCLUSION: The etiological investigation in retinal vein occlusion in
      young people must be exhaustive. The visual prognosis is variable and may depend
      on the etiology.

PMID- 20031257
TI  - [Unilateral acute endophthalmitis due to Staphylococcus epidermidis after
      simultaneous bilateral intravitreal injection using the same ranibizumab vial: a
      case report].
AB  - PURPOSE: To report a case of unilateral acute endophthalmitis due to
      Staphylococcus epidermidis after simultaneous bilateral intravitreal injection
      using the same ranibizumab vial. CASE REPORT: A 68-year-old phakic man had
      uneventful bilateral sequential ranibizumab intravitreal injection for bilateral
      neovascular age-related macular degeneration using the same vial. All of the vial
      contents (0.3 mL) were withdrawn through the filter needle attached to a 1-cc
      tuberculin syringe. Using the same syringe but separate injection needles, 0.05
      mL was administrated to the right eye before 0.05 mL was injected into the left
      eye. Sterile gloves, drape, and eyelid speculum were used for each eye. Early
      Staphylococcus epidermidis postoperative endophthalmitis developed 3 days later
      in the right eye (injected first) with intense vitreous inflammation, limiting
      visual acuity to light perception. Management included intravitreal antibiotic
      agents and pars plana vitrectomy. The patient achieved an excellent visual
      outcome. DISCUSSION: This case report demonstrates that bacterial endophthalmitis
      is a rare but potential complication of intravitreal anti-VEGF injection, that
      infection generally results from self-contamination of the patient from his or
      her own bacterial flora, and that simultaneous bilateral intravitreal injection
      should be avoided.

PMID- 20031258
TI  - [Lipemia retinalis: a sign of a severe hypertriglyceridemia].

PMID- 20031259
TI  - [Iatrogenic disease: role of ophthalmologists].

PMID- 20031260
TI  - [Effects of spherical aberration on objective optical quality after microincision
      cataract surgery].
AB  - PURPOSE: To assess the impact of spherical aberration (SA) on clinical ocular
      performance and the objective quality of vision in pseudophakic patients.
      METHODS: Twenty-five consecutive eyes were divided into two groups: 13 eyes
      received an aspherical AcriSmart 36A intraocular lens (IOL) (Carl Zeiss Meditec,
      USA) generating a negative SA and 12 eyes received a zero-aberration AcriSmart 46
      LC IOL (Carl Zeiss Meditec, USA). Postoperative evaluations were conducted 6
      months after 1.8-mm microincision cataract surgery and included wavefront
      aberration analysis (Wavescan, AMO, USA) and objective quality of vision
      (Objective Quality Analysis System, Visiometrics, Spain). RESULTS: Best corrected
      visual acuity (BCVA) was not different in the two groups (p=0.89). Total
      spherical aberration was significantly less with the 36A IOL (0.075 +/- 0.05
      microm versus 0.20 +/- 0.05 microm; p=0.0002). The 36A IOL induced better
      objective image quality with an average MTF of 32.7+/-9.6 c/deg versus 23.8+/-8.1
      c/deg with the 46LC, p=0.0002. The 36A IOL group had 1 D less depth of focus than
      the 46LC IOL group: 1.3+/-0.59 and 2.27+/-0.63 D, respectively. For the whole
      population, the depth of focus appeared to be correlated with SA (r(2)=0.40,
      p=0.002) and with trefoil (r(2)=0.53, p=0.001). CONCLUSION: Aspheric IOLs
      objectively improved the quality of vision with greater MTF values. Reduction of
      aberrations may be also be responsible for reduced depth of focus with the 36A
      IOLs. However, residual trefoil aberrations may be advantageous for depth of
      focus.

PMID- 20031261
TI  - [Branch retinal artery occlusion as the sole ocular manifestation of Takayasu
      arteritis].
AB  - We report a case of branch retinal artery occlusion in a young woman suffering
      from established Takayasu arteritis. A 35-year-old woman with a previous history
      of Takayasu arteritis, diagnosed 5 years before, presented to the emergency
      department reporting sudden visual loss in her left eye and restriction of the
      visual field for the past hour. On ophthalmologic examination, occlusion of the
      superior temporal branch of the central retinal artery was revealed. However, no
      other classic signs of ocular ischemia associated with Takayasu arteritis were
      observed. Three out of the six criteria set out by the American College of
      Rheumatology for the diagnosis of Takayasu disease were met. Visual acuity
      recovered to 7/10(e), corrected, with the presence of a patent cilioretinal
      artery. The occurrence of retinal artery occlusion at such a young age is
      exceptional, justifying a thorough examination to reveal the underlying
      pathology. There is only one other report in the literature of a case of branch
      retinal artery occlusion as a manifestation of Takayasu arteritis. The case
      reported here is exceptional because of the absence of more typical signs of
      ocular ischemia and the moderate degree of involvement of the major cervical
      arteries.

PMID- 20031262
TI  - Just say no: gastric aspiration and lavage rarely provide benefit.

PMID- 20031263
TI  - Patient identification errors are common in a simulated setting.
AB  - STUDY OBJECTIVE: We evaluate the frequency and accuracy of health care workers
      verifying patient identity before performing common tasks. METHODS: The study
      included prospective, simulated patient scenarios with an eye-tracking device
      that showed where the health care workers looked. Simulations involved nurses
      administering an intravenous medication, technicians labeling a blood specimen,
      and clerks applying an identity band. Participants were asked to perform their
      assigned task on 3 simulated patients, and the third patient had a different date
      of birth and medical record number than the identity information on the artifact
      label specific to the health care workers' task. Health care workers were unaware
      that the focus of the study was patient identity. RESULTS: Sixty-one emergency
      health care workers participated--28 nurses, 16 technicians, and 17 emergency
      service associates--in 183 patient scenarios. Sixty-one percent of health care
      workers (37/61) caught the identity error (61% nurses, 94% technicians, 29%
      emergency service associates). Thirty-nine percent of health care workers (24/61)
      performed their assigned task on the wrong patient (39% nurses, 6% technicians,
      71% emergency service associates). Eye-tracking data were available for 73% of
      the patient scenarios (133/183). Seventy-four percent of health care workers
      (74/100) failed to match the patient to the identity band (87% nurses, 49%
      technicians). Twenty-seven percent of health care workers (36/133) failed to
      match the artifact to the patient or the identity band before performing their
      task (33% nurses, 9% technicians, 33% emergency service associates). Fifteen
      percent (5/33) of health care workers who completed the steps to verify patient
      identity on the patient with the identification error still failed to recognize
      the error. CONCLUSION: Wide variation exists among health care workers verifying
      patient identity before performing everyday tasks. Education, process changes,
      and technology are needed to improve the frequency and accuracy of patient
      identification.

PMID- 20031264
TI  - Nasogastric aspiration: a useful tool in some patients with gastrointestinal
      bleeding.

PMID- 20031265
TI  - Ondansetron use in the pediatric emergency department and effects on
      hospitalization and return rates: are we masking alternative diagnoses?
AB  - STUDY OBJECTIVE: We evaluate the effect of ondansetron use in cases of suspected
      gastroenteritis on the proportion of hospital admissions and return visits and
      assess whether children who receive ondansetron on their initial visit to the
      pediatric emergency department (ED) for suspected gastroenteritis return with an
      alternative diagnosis more frequently than those who did not receive ondansetron.
      METHODS: This is a retrospective review of visits to 2 tertiary care pediatric
      EDs with an International Classification of Diseases, Ninth Revision diagnosis of
      vomiting or gastroenteritis. A logistic regression model was developed to
      determine the effect of ondansetron use during the initial pediatric ED visit on
      hospital admission, return to the pediatric ED within 72 hours, and admission on
      this return visit. For patients who returned within 72 hours and were admitted,
      hospital discharge records were reviewed. The proportions of alternative
      diagnoses, defined as a hospital discharge diagnosis that was not a continuation
      of gastroenteritis or vomiting, were compared between the groups. RESULTS: During
      the 3-year study period (2005 to 2007), 34,117 patients met study criteria.
      Ondansetron was used for 19,857 (58.2%) of these patients on their initial
      pediatric ED visit. After controlling for differences between the groups,
      patients who received ondansetron were admitted on their initial visit less
      often: odds ratio (OR) 0.47 (95% confidence interval [CI] 0.42 to 0.53). However,
      those who received ondansetron were more likely to return to the pediatric ED
      within 72 hours (OR 1.45; 95% CI 1.27 to 1.65) and be admitted on the return
      visit (OR 1.74; 95% CI 1.39 to 2.19). The proportions of alternative diagnoses at
      hospital discharge were not significantly different in the group that received
      ondansetron on the initial pediatric ED visit (14.9%) compared with the group
      that did not (22.4%) (absolute difference 7.5% [95% CI -0.5% to 16.4%).
      CONCLUSION: Ondansetron use in the pediatric ED reduces hospital admissions for
      suspected gastroenteritis and vomiting. However, children who receive ondansetron
      in the pediatric ED appear more likely to return to the pediatric ED and be
      admitted on this return visit than their counterparts. Furthermore, the use of
      ondansetron does not appear to be associated with increased risks of masking
      serious diagnoses in children.

PMID- 20031266
TI  - Effective clinical teaching by residents in emergency medicine.

PMID- 20031267
TI  - Confusion about epinephrine dosing leading to iatrogenic overdose: a life
      threatening problem with a potential solution.
AB  - Epinephrine is indicated for various medical emergencies, including cardiac
      arrest and anaphylaxis, but the dose and route of administration are different
      for each indication. For anaphylaxis, it is given intramuscularly at a low dose,
      whereas for cardiac arrest a higher dose is required intravenously. We
      encountered a patient with suspected anaphylaxis who developed transient severe
      systolic dysfunction because of inappropriately received cardiac arrest dose, ie,
      larger dose given as an intravenous push. Three additional patients who
      experienced potentially lethal cardiac complications after receiving
      inappropriately higher doses intravenously were also identified. These iatrogenic
      errors resulted from underlying confusion by physicians about proper dosing of
      epinephrine for anaphylaxis. The risk of error was amplified by the need for
      rapid decision making in critically ill anaphylactic patients. An e-mail survey
      of local hospitals in southeast Michigan revealed that 6 of 7 hospitals did not
      stock prefilled intramuscular dose syringes for emergency use in anaphylaxis. At
      our institution, we have introduced prefilled and appropriately labeled
      intramuscularly dosed epinephrine syringes in crash carts, which are easily
      distinguished from intravenously dosed epinephrine syringes. In this Concepts
      article, we describe the clinical problem of inadvertent epinephrine overdose and
      propose a potential solution. Epinephrine must be clearly packaged and labeled to
      avoid inappropriate usage and unnecessary, potentially lethal complications in
      patients with anaphylaxis.

PMID- 20031268
TI  - Pediatric subperiosteal orbital abscess secondary to acute sinusitis: a 5-year
      review.
AB  - OBJECTIVE: Subperiosteal orbital abscesses (SPOAs) secondary to acute sinusitis
      are rare occurrences in the pediatric age group, more so in the neonatal period.
      Here, a rare case of SPOA in a 38-day-old newborn later drained via endoscopic
      sinus surgery is included also. This review describes the demographic data,
      clinical history, treatment, microbiology results, complications, and outcome.
      METHODS: The admission records for all the patients who were admitted to the
      Pediatric Surgical Ward in Sarawak General Hospital, Kuching, Malaysia, between
      January 2004 and May 2009 were retrospectively reviewed. Records of patients who
      presented with preseptal cellulitis, orbital cellulitis, subperiosteal abscess
      (extraconal), orbital abscess (intraconal), and cavernous sinus thrombosis were
      closely studied. Ophthalmology consultations were obtained in all these cases.
      Ultimately, 3 patients having SPOA secondary to acute sinusitis were selected for
      this review. RESULTS: All patients were male with rapid onset of periorbital
      signs, absence of purulent rhinorrhea, and presence of significant thrombocytosis
      (exceeding 500 * 10(9)/L). The 38-day-old newborn had mixed infection of
      methicillin-resistant coagulase-negative Staphylococcus bacteremia and local
      Acinetobacter eye infection with Staphylococcus aureus in the SPOA. All had
      medially located SPOA that was adequately drained via endoscopic sinus surgery,
      resulting in full recovery. CONCLUSION: Newborns with preexisting risk factors
      and immature immunity are at risk of severe and rare infections. Contrast
      enhanced paranasal sinus computed tomographic scan is mandatory and reliable to
      differentiate preseptal and postseptal orbital infection, as both conditions can
      present similarly and rapidly deteriorate. In the contrast-enhanced computed
      tomography-demonstrable SPOA, endoscopic sinus surgery drainage of the abscess
      proved to be safe and reliable as the main treatment modality. All patients
      recovered well without complications.

PMID- 20031269
TI  - Metastasis to head and neck area: a 16-year retrospective study.
AB  - PURPOSE: One of the most striking qualities of cancer is its spread throughout
      the body. The location of a metastatic mass may help to identify the primary
      tumor. Metastases to head and neck area can occur either from local structures or
      from distant organs. MATERIALS AND METHODS: This study was a retrospective review
      of patients from a University Hospital in Tehran, Iran, during the period 1992 to
      2008. The data were analyzed for sex, age, primary site of tumors, metastatic
      site, and histology of the tumors. The tumors were classified into 2 groups:
      intraoral and extraoral. RESULTS: A total of 191 cases were found; of these, 118
      (62%) were men and 73 (38%) were women. The most common intraoral primary site
      was tongue (anterior and posterior parts). Thyroid gland was the most frequent
      primary extraoral site. The most frequent metastatic site was the lymph node, and
      level II most commonly involved lymph nodes, followed by level I. CONCLUSION:
      Metastases are an infrequent finding in head and neck region and they may
      represent the initial manifestation of the disease. Diagnostic evaluation of
      metastatic lesion will detect the primary tumor.

PMID- 20031270
TI  - Contamination of intravenous fluids: a continuing cause of hospital bacteremia.
AB  - BACKGROUND: Nosocomial bacteremia caused by the contamination of intravenous (IV)
      infusates is considered rare. Unfortunately, this problem has been underestimated
      because its identification requires culturing infusates, a procedure not
      performed routinely. METHODS: This study was conducted in a referral hospital
      where IV infusates are admixed in nursing areas. The aim was to determine the
      prevalence of infusate contamination in adult patients with gram-negative rod
      (GNR) bacteremia. Over a period of 32 months, a specimen of infusate was drawn
      for culture from each patient recruited after the laboratory reported a GNR in
      the blood. RESULTS: A total of 384 infusates were cultured from 384 patients who
      had been diagnosed with GNR bacteremia. Seven infusates grew a GNR in culture,
      for a contamination rate of 2% (7/384; 95% confidence interval [CI] = 1% to 3%).
      In all cases, the infectious organism was the same as the organism isolated from
      the blood. Infusate contamination was responsible for 7% (7/108; 95% CI = 2% to
      11%) of all primary bloodstream infections and 11% (7/62; 95% CI = 2% to 22%) of
      all primary bloodstream infections not associated with central venous catheter
      infection. CONCLUSIONS: For patients in hospitals where IV drugs are admixed in
      nursing units, we recommend instituting infusate culture as routine practice
      following the diagnosis of a GNR in the blood.

PMID- 20031271
TI  - Notifiable infectious disease reporting awareness among physicians and registered
      nurses in primary care and emergency department settings.
AB  - This study examined knowledge about notifiable infectious disease reporting among
      physicians and registered nurses (RNs) in primary care and emergency department
      settings in King County, Washington. In 2005, a total of 165 physicians and 170
      RNs completed a questionnaire to assess knowledge, training and feedback
      regarding notifiable infectious disease reporting. Only 55% of the physicians and
      63% of the RNs were aware of reporting procedures within their institution.
      Awareness was higher when employer-provided training had been provided. Our
      findings indicate that employer training can improve reporting knowledge.

PMID- 20031272
TI  - Effect of temporal lobe structure volume on memory in elderly depressed patients.
AB  - OBJECTIVE: To compare the volume of the hippocampus and parahippocampal gyrus in
      elderly individuals with and without depressive disorders, and to determine
      whether the volumes of these regions correlate with scores on memory tests.
      METHOD: Clinical and demographic differences, as well as differences in regional
      gray matter volumes, were assessed in 48 elderly patients with depressive
      disorders and 31 control subjects. Brain (structural MRI) scans were processed
      using statistical parametric mapping and voxel-based morphometry. Cognitive tests
      were administered to subjects in both groups. RESULTS: There were no between
      group gray matter volume differences in the hippocampus or parahippocampal gyrus.
      In the elderly depressed group only, the volume of the left parahippocampal gyrus
      correlated with scores on the delayed naming portion of the visual-verbal
      learning test. There were also significant direct correlations in depressed
      subjects between the volumes of the left hippocampus, right and left
      parahippocampal gyrus and immediate recall scores on verbal episodic memory tests
      and visual learning tests. In the control group, there were direct correlations
      only between overall cognitive performance (as assessed with the MMSE) and the
      volume of right hippocampus, and between the total score on the visual-verbal
      learning test and the volume of the right and left parahippocampal gyrus.
      CONCLUSIONS: These findings highlight different patterns of relationship between
      cognitive performance and volumes of medial temporal structures in depressed
      individuals and healthy elderly subjects. The direct correlation between delayed
      visual-verbal memory recall scores with left parahippocampal volumes specifically
      in elderly depressed individuals provides support to the view that depression in
      elderly populations may be a risk factor for dementia.

PMID- 20031273
TI  - Telomere length and cognitive function in community-dwelling elders: findings
      from the Health ABC Study.
AB  - Telomere shortening is a marker of cellular aging and has been associated with
      risk of Alzheimer's disease. Few studies have determined if telomere length is
      associated with cognitive decline in non-demented elders. We prospectively
      studied 2734 non-demented elders (mean age: 74 years). We measured cognition with
      the Modified Mini-Mental State Exam (3MS) and Digit Symbol Substitution Test
      (DSST) repeatedly over 7 years. Baseline telomere length was measured in blood
      leukocytes and classified by tertile as "short", "medium", or "long". At
      baseline, longer telomere length was associated with better DSST score (36.4,
      34.9 and 34.4 points for long, medium and short, p<0.01) but not for change in
      score. However, 7-year 3MS change scores were less among those with longer
      telomere length (-1.7 points vs. -2.5 and -2.9, p=0.01). Findings were similar
      after multivariable adjustment for age, gender, race, education, assay batch, and
      baseline score. There was a borderline statistically significant interaction for
      telomere length and APOE e4 on 3MS change score (p=0.06). Thus, telomere length
      may serve as a biomarker for cognitive aging.

PMID- 20031274
TI  - Persistent increase of D-aspartate in D-aspartate oxidase mutant mice induces a
      precocious hippocampal age-dependent synaptic plasticity and spatial memory
      decay.
AB  - The atypical amino acid d-aspartate (d-Asp) occurs at considerable amounts in the
      developing brain of mammals. However, during postnatal life, d-Asp levels
      diminish following the expression of d-aspartate oxidase (DDO) enzyme. The strict
      control of DDO over its substrate d-Asp is particularly evident in the
      hippocampus, a brain region crucially involved in memory, and highly vulnerable
      to age-related deterioration processes. Herein, we explored the influence of
      deregulated higher d-Asp brain content on hippocampus-related functions during
      aging of mice lacking DDO (Ddo(-/-)). Strikingly, we demonstrated that the
      enhancement of hippocampal synaptic plasticity and cognition in 4/5-month-old
      Ddo(-/-) mice is followed by an accelerated decay of basal glutamatergic
      transmission, NMDAR-dependent LTP and hippocampus-related reference memory at
      13/14 months of age. Therefore, the precocious deterioration of hippocampal
      functions observed in mutants highlights for the first time a role for DDO enzyme
      in controlling the rate of brain aging process in mammals.

PMID- 20031275
TI  - Mutational analysis of TARDBP in neurodegenerative diseases.
AB  - Neurodegenerative diseases are often characterized by the presence of aggregates
      of misfolded proteins. TDP-43 is a major component of these aggregates in
      amyotrophic lateral sclerosis (ALS), but has also been observed in Alzheimer's
      (AD) and Parkinson's Diseases (PD). In addition, mutations in the TARDBP gene,
      encoding TDP-43, have been found to be a significant cause of familial ALS
      (FALS). All mutations, except for one, have been found in exon 6. To confirm this
      observation in ALS and to investigate whether TARDBP may play a role in the
      pathogenesis of AD and PD, we screened for mutations in exon 6 of the TARDBP gene
      in three cohorts composed of 376 AD, 463 PD (18% familial PD) and 376 ALS
      patients (50% FALS). We found mutations in ~ 7% of FALS and ~0.5% of sporadic ALS
      (SALS) patients, including two novel mutations, p.N352T and p.G384R. In contrast,
      we did not find TARDBP mutations in our cohort of AD and PD patients. These
      results suggest that mutations in TARDBP are not a significant cause of AD and
      PD.

PMID- 20031276
TI  - Insulin resistance and hippocampal volume in women at risk for Alzheimer's
      disease.
AB  - Insulin resistance (IR) is the main pathological condition underlying vascular
      disorders, such as diabetes and cardiovascular disease, which are well
      established risk factors for cognitive decline and Alzheimer disease (AD).
      Hippocampal atrophy has been associated with cognitive decline, but little is
      known about the influence of IR on hippocampus integrity in non-diabetic,
      cognitively intact individuals. Herein, 50 women ages 50-65, current users of
      hormone therapy, underwent magnetic resonance imaging, cognitive testing, and
      homeostatic assessment of insulin resistance (HOMA-IR), as part of a longitudinal
      study examining brain structure and function in postmenopausal women at risk for
      AD. Results demonstrated a significant negative relationship between HOMA-IR and
      right and total hippocampal volume, overall cognitive performance, and selective
      tests of verbal and non-verbal memory. The main effect of HOMA-IR on brain
      structure and cognition was not altered by the presence of APOE-epsilon4 allele
      or by reproductive history, such as duration of endogenous and exogenous estrogen
      exposure. These results suggest that IR in middle-aged individuals at risk for AD
      may be biomarker for dementia risk.

PMID- 20031277
TI  - Declining phosphatases underlie aging-related hyperphosphorylation of
      neurofilaments.
AB  - Cytoskeletal protein phosphorylation is frequently altered in neuropathologic
      states but little is known about changes during normal aging. Here we report that
      declining protein phosphatase activity, rather than activation of kinases,
      underlies aging-related neurofilament hyperphosphorylation. Purified PP2A or PP2B
      dephosphorylated the heavy neurofilament (NFH) subunit or its extensively
      phorphorylated carboxyl-terminal domain in vitro. In cultured primary hippocampal
      neurons, inhibiting either phosphatase induced NFH phosphorylation without
      activating known neurofilament kinases. Neurofilament phosphorylation in the
      mouse CNS, as reflected by levels of the RT-97 phosphoepitope associated with
      late axon maturation, more than doubled during the 12-month period after NFH
      expression plateaued at p21. This was accompanied by declines in levels and
      activity of PP2A but not PP2B, and no rise in activities of neurofilament kinases
      (Erk1,2, cdk5 and JNK1,2). Inhibiting PP2A in mice in vivo restored brain RT-97
      to levels seen in young mice. Declining PP2A activity, therefore, can account for
      rising neurofilament phosphorylation in maturing brain, potentially compounding
      similar changes associated with adult-onset neurodegenerative diseases.

PMID- 20031279
TI  - [Does a history of substance abuse influence sedation requirements in critically
      ill patients?].

PMID- 20031278
TI  - Cognitive effects of cell-derived and synthetically derived Abeta oligomers.
AB  - Soluble forms of amyloid-beta peptide (Abeta) are a molecular focus in
      Alzheimer's disease research. Soluble Abeta dimers (~8 kDa), trimers (~12 kDa),
      tetramers (~16 kDa) and Abeta*56 (~56 kDa) have shown biological activity. These
      Abeta molecules have been derived from diverse sources, including chemical
      synthesis, transfected cells, and mouse and human brain, leading to uncertainty
      about toxicity and potency. Herein, synthetic Abeta peptide-derived oligomers,
      cell- and brain-derived low-n oligomers, and Abeta*56, were injected
      intracerebroventricularly (icv) into rats assayed under the Alternating Lever
      Cyclic Ratio (ALCR) cognitive assay. Cognitive deficits were detected at 1.3 MUM
      of synthetic Abeta oligomers and at low nanomolar concentrations of cell-secreted
      Abeta oligomers. Trimers, from transgenic mouse brain (Tg2576), did not cause
      cognitive impairment at any dose tested, whereas Abeta*56 induced concentration
      dependent cognitive impairment at 0.9 and 1.3MUM. Thus, while multiple forms of
      Abeta have cognition impairing activity, there are significant differences in
      effective concentration and potency.

PMID- 20031280
TI  - [Treatment of diseases caused by parasites].
AB  - Parasitic infections occur worldwide and cause significant morbidity and
      mortality, especially in tropical areas. In recent years, the interest in these
      infections has grown because of the increase in immigration, international
      travel, and international adoptions. In Spain, these factors have led to a rise
      in the incidence of parasitic infections. The typical profile of travelers has
      also changed, with an increase in immunosuppressed persons, and those of advanced
      age or with pre-existing medical conditions. Immigrants who have settled in host
      countries often return to their countries of origin to visit friends and
      relatives, and these travelers are at a higher risk of acquiring certain
      infections. Immigrants may be blood or organ donors, and transmission of exotic
      infections may occur. This review summarizes the management of the most frequent
      parasitic infections at a time when clinical parasitology is of considerable
      interest.

PMID- 20031281
TI  - Synthesis, antibacterial and antifungal activities of 6,5 fused steroidal
      oxazoles in cholestane series.
AB  - Herein, we report a convenient one-pot synthesis of 2'-amino-5alpha-cholest-6-eno
      [6,5-d] oxazole derivatives (4-6). The synthesis involves the reaction of
      cholestan-6-ones (1-3) with urea and iodine. The structural assignment of the
      products was confirmed on the basis of IR, (1)H NMR, (13)C NMR, and Mass spectra
      which find support from comparison with authentic samples. The antibacterial
      activity of all the synthesized compounds was tested in vitro by the disk
      diffusion assay against three Gram-positive and three Gram-negative strains of
      bacteria. All the synthesized compounds were also tested for their inhibitory
      action against five strains of fungus and then the minimum inhibitory
      concentration (MIC) of all the synthesized compounds were determined. Compounds
      (4-6) showed inhibitory action against both types of the bacteria (Gram-positive
      and Gram-negative) and five strains of fungi are good antimicrobial agents.
      Chloramphenicol (30 microg) was used as standard drug in case of bacteria and
      nystatin was used as a standard drug in case of fungi.

PMID- 20031282
TI  - QSAR study on melanocortin-4 receptors by support vector machine.
AB  - Quantitative structure activity relationship (QSAR) of the melanocortin-4
      receptor (MC4R) binding affinities (K(i)) of trans-4-(4-chlorophenyl) pyrrolidine
      3-carboxamides of piperazinecyclohexanes was studied. A suitable set of molecular
      descriptors was calculated and the genetic algorithm (GA) was employed to select
      those descriptors that resulted in the best-fit models. The multiple linear
      regression (MLR), and the support vector machine (SVM) were utilized to construct
      the linear and nonlinear QSAR models. The models were validated using Leave-One
      Out (LOO) and Leave-Group-Out (LGO) cross-validation, external test set, and
      chance correlation. The SVM model generalizes better than the MLR model. The SVM
      model, with high statistical significance (R(2)(train)=0.908, Q(2)(LOO)=0.781,
      Q(2)(LGO)=0.872), could be used to predict melanocortin-4 receptor binding
      affinities of piperazinecyclohexanes.

PMID- 20031283
TI  - Incorporating a research apprenticeship model in a Canadian nursing Honors
      Program.
AB  - In this article, we describe the development of a BScN (Honors) Program in a
      large Canadian university. We describe the elements of the program, including the
      application of a research apprenticeship model as the core of the program. We
      provide examples of student learning experiences culminating in the Honors
      project. Recruitment, balancing clinical and research interests, financial
      support, and manageability of the Honors project emerged as key challenges in our
      first offerings of the program. Overall, students perceived that experiential
      research learning enhanced their research skills, increased appreciation of the
      process and outcomes of nursing research, and inspired confidence to pursue
      graduate education. We conclude that an apprenticeship model providing students
      with experiential research learning with established faculty researchers is an
      effective and efficient way to deliver the Honors Program in the context of a
      research-intensive nursing faculty.

PMID- 20031284
TI  - Use of Lugol's iodine in the resection of oral and oropharyngeal squamous cell
      carcinoma.
AB  - We evaluated the use of Lugol's iodine in achieving surgical margins free from
      dysplasia, carcinoma in situ, and invasive carcinoma by an observational study of
      two series of 50 consecutive patients having resection of oral and oropharyngeal
      squamous cell carcinoma (SCC) between November 2004 and March 2007. The standard
      group had resection of the primary tumour with a macroscopic 1cm margin and
      removal of adjacent visibly abnormal mucosa. The Lugol's iodine group had
      identical treatment with resection of any adjacent mucosa that did not stain
      after the application of Lugol's iodine (where this was feasible). In the
      standard group 16 patients (32%) had dysplasia, carcinoma in situ, or invasive
      SCC at a surgical margin. In the Lugol's iodine group two patients (4%) had
      dysplasia or carcinoma in situ; none had invasive SCC. Lugol's iodine is a
      simple, inexpensive, and apparently effective means of reducing the likelihood of
      unsatisfactory surgical margins in the resection of oral and oropharyngeal SCC.

PMID- 20031285
TI  - Enhanced reductive dechlorination of DDT in an anaerobic system of dissimilatory
      iron-reducing bacteria and iron oxide.
AB  - The transformation of DDT was studied in an anaerobic system of dissimilatory
      iron-reducing bacteria (Shewanella decolorationis S12) and iron oxide (alpha
      FeOOH). The results showed that S. decolorationis could reduce DDT into DDD, and
      DDT transformation rate was accelerated by the presence of alpha-FeOOH. DDD was
      observed as the primary transformation product, which was demonstrated to be
      transformed in the abiotic system of Fe(2+)+alpha-FeOOH and the system of
      DIRB+alpha-FeOOH. The intermediates of DDMS and DBP were detected after 9 months,
      likely suggesting that reductive dechlorination was the main dechlorination
      pathway of DDT in the iron-reducing system. The enhanced reductive dechlorination
      of DDT was mainly due to biogenic Fe(II) sorbed on the surface of alpha-FeOOH,
      which can serve as a mediator for the transformation of DDT. This study
      demonstrated the important role of DIRB and iron oxide on DDT and DDD
      transformation under anaerobic iron-reducing environments.

PMID- 20031286
TI  - Trace element mobility in a contaminated soil two years after field-amendment
      with a greenwaste compost mulch.
AB  - Application of greenwaste compost to brownfield land is increasingly common in
      soil and landscape restoration. Previous studies have demonstrated both
      beneficial and detrimental effects of this material on trace element mobility. A
      pot experiment with homogenised soil/compost investigated distribution and
      mobility of trace elements, two years after application of greenwaste compost
      mulch to shallow soils overlying a former alkali-works contaminated with Pb, Cu
      and As (approximately 900, 200 and 500 mg kg(-1), respectively). Compost mulch
      increased organic carbon and Fe in soil pore water, which in turn increased As
      and Sb mobilization; this enhanced uptake by lettuce and sunflower. A very small
      proportion of the total soil trace element pool was in readily-exchangeable form
      (<0.01% As, <0.001% other trace elements), but the effect of compost on behaviour
      of metals was variable and ambiguous. It is concluded that greenwaste compost
      should be applied with caution to multi-element contaminated soils.

PMID- 20031287
TI  - Impact of erythropoiesis-stimulating agents on energy and physical function in
      nondialysis CKD patients with anemia: a systematic review.
AB  - BACKGROUND: Previous analyses report the impact of erythropoiesis-stimulating
      agents (ESAs) on health-related quality of life across various populations. In
      this analysis, we review published studies and quantify the effect of ESA therapy
      on energy/fatigue and physical function in nondialysis patients with chronic
      kidney disease (CKD) related anemia. STUDY DESIGN: Systematic literature search
      to identify articles (1980-2008) that evaluated effects of ESAs on patient
      reported energy and physical function. SETTING & POPULATION: Nondialysis CKD
      patients with anemia enrolled in prospective trials. SELECTION CRITERIA FOR
      STUDIES: Prospective studies measuring energy or physical function with both
      baseline and follow-up measurement. INTERVENTION: ESA treatment. OUTCOMES:
      Improvements in energy and physical function assessed using effect size, a
      measure of treatment responsiveness. RESULTS: 14 studies were identified: 11
      measured energy and 14 measured physical function. The 36-Item Short-Form Health
      Survey (SF-36) was the most common instrument used to report energy and physical
      function. Of 11 studies measuring energy, 2 were double-blind randomized placebo
      controlled trials (RCTs), 5 were open-label RCTs, and 4 were single-arm open
      label studies. Eight of 11 studies reported statistically significant
      improvements in energy. Effect size for energy ranged from small (0.24) to large
      (1.90) in ESA-treated groups and was moderate in each arm of the low- versus high
      hemoglobin target RCTs. Of 14 studies measuring physical function, 2 were double
      blind RCTs, 6 were open-label RCTs, and 6 were single-arm open-label studies. Ten
      of 14 studies reported statistically significant improvements in physical
      function. Effect size for physical function ranged from small (0.37) to large
      (2.38) in ESA-treated groups and was negligible to moderate in each arm of low-
      versus high-hemoglobin target studies. LIMITATIONS: Findings and conclusions were
      limited by the available evidence. CONCLUSION: RCTs and single-arm studies
      indicate that treatment of anemia with ESAs improves energy and physical function
      in nondialysis CKD patients.

PMID- 20031288
TI  - Surgical approach to impacted mandibular third molars--operative classification.
AB  - PURPOSE: The aim of the present study is to suggest a convenient way to classify
      the position of the impacted third mandibular molar relative to the mandibular
      canal and to suggest indications for the use of each surgical approach for
      mandibular third molar extraction. MATERIALS AND METHODS: The presented new
      typing system, Third Molar Classification (TMC), is a simple and easy-to-apply
      method for the surgical management of mandibular third molars and can be extended
      for any ectopic or impacted mandibular tooth. There are 3 major types of third
      molar positions. The second type is subdivided further into 2 subtypes. In the
      present study, 9 patients with high-risk mandibular third molars were treated
      according to the present classification and are presented and discussed. Patients
      typed as TMC IIb were treated with a sagittal split osteotomy approach and
      patients typed as TMC III were treated with an extraoral approach. RESULTS: The
      operative classification was successfully implemented in very rare cases of
      deeply impacted mandibular third molars. In 3 of 9 cases (33%) minor
      complications included some degree of hypoesthesia using the extraoral approach;
      these complications resolved spontaneously without the need for any intervention.
      CONCLUSIONS: The present study describes the use of a new surgical classification
      system for treatment planning in all types of mandibular third molar extractions.
      We believe that the present classification could help the oral and maxillofacial
      surgeon in decision-making and limit the possible risks that are present when
      attempting to extract impacted mandibular third molars.

PMID- 20031289
TI  - Relationship of synovial tumor necrosis factor alpha and interleukin 6 to
      temporomandibular disorder.
AB  - PURPOSE: The purpose of this study was to elucidate the relationship of tumor
      necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) to temporomandibular
      disorder with clinical symptoms such as pain, joint sounds, and mouth opening
      limitation by analysis of the level of these molecules in the synovial fluid.
      PATIENTS AND METHODS: Twenty-four patients with chief complaints of pain, mouth
      opening limitation, and clicking sounds were selected as the experimental group
      and compared with 5 healthy subjects. After joint lavage with arthrocentesis,
      diluted synovial fluid was collected and enzyme-linked immunosorbent assay was
      done for analysis of TNF-alpha and IL-6 in 24 experimental patients and 5 healthy
      subjects. RESULTS: The synovial levels of TNF-alpha and IL-6 were elevated in the
      experimental group compared with the healthy control group, but no significant
      correlation was established. The synovial levels of TNF-alpha and IL-6 were
      elevated in the acute pain group compared with the chronic pain group, but no
      significant correlation was established. CONCLUSION: In our analysis of 2
      proinflammatory cytokines, TNF-alpha and IL-6, in the synovial fluid of
      temporomandibular disorder patients with symptoms of pain, mouth opening
      limitation, and clicking, both were elevated without statistical significance.

PMID- 20031290
TI  - Felypressin, but not epinephrine, reduces myocardial oxygen tension after an
      injection of dental local anesthetic solution at routine doses.
AB  - PURPOSE: The aim of this study was to evaluate the effect of epinephrine (Epi) or
      felypressin (Fely) contained in dental local anesthetics on myocardial oxygen
      balance. MATERIALS AND METHODS: Male Japanese White tracheotomized rabbits were
      anesthetized with isoflurane. Three doses of 0.18, 0.36, and 0.72 mL of 2%
      lidocaine hydrochloride containing 1:80,000 Epi or 3% prilocaine hydrochloride
      containing Fely 0.03 IU/mL were injected into the rabbit tongue muscle. These
      doses were equivalent to 2, 4, and 8 of dental local anesthetic cartridges in
      humans weighing 50 kg by body weight correction, respectively. Heart rate, blood
      pressure, aortic blood flow, myocardial tissue blood flow, and myocardial tissue
      oxygen tension were continuously monitored. Data were recorded immediately before
      and 10, 20, 30, and 60 minutes after the injection. RESULTS: Heart rate decreased
      in the Fely group. Systolic blood pressure increased in the Epi group, and
      diastolic blood pressure increased in both groups. Aortic blood flow and
      myocardial tissue blood flow increased, whereas myocardial tissue oxygen tension
      did not change in the Epi group. In contrast, aortic blood flow, myocardial
      tissue blood flow, and myocardial tissue oxygen tension decreased in the Fely
      group. CONCLUSION: It is suggested that Fely, but not Epi, decreases myocardial
      oxygen tension and aggravates myocardial oxygen demand/supply balance even after
      an injection of dental local anesthetic solution at routine doses.

PMID- 20031291
TI  - Ultrasonography for intraoperative determination of tumor thickness and resection
      margin in tongue carcinomas.
AB  - PURPOSE: Exact estimation of tumor thickness and the status of the resection
      margin in tongue carcinoma are important prognostic factors for local recurrence,
      subclinical nodal metastasis, and survival. This study aims to evaluate the
      accuracy of intraoral ultrasonography-guided measurement of tumor thickness and
      define an adequate intraoperative resection margin in squamous cell carcinomas of
      the tongue. MATERIALS AND METHODS: In this prospective study, 13 patients with
      presurgical, biopsy-proven, clinical T1N0 or T2N0 tongue squamous cell carcinomas
      who underwent a partial glossectomy were examined preoperatively with
      ultrasonography to assess tumor thickness under general anesthesia. Nine cases
      underwent resection by a conventional method, whereas we introduced elastic
      needles with a metal core to mark a deep surgical margin of 10 mm from the
      deepest tumor invasion front under ultrasonographic monitoring as a new technique
      in the remaining 4 cases. Each resected specimen was immediately immersed in
      gelatin solution while maintaining its original shape and orientation and was
      placed under refrigeration to solidify. Ultrasonographic observations of the
      gelatin-embedded specimens were performed from the superior surface of the
      gelatin block. RESULTS: Very fine ultrasonographic images of the resected
      specimen could be easily obtained without any special skills, and surgical
      clearance could be verified intraoperatively. The ultrasonographic tumor
      thickness measurements corresponded well with those of histologic sections, with
      a consistency ratio of 91.4% to 98.2% (Pearson correlation coefficient = 0.981, P
      < .05). CONCLUSION: Intraoperative ultrasonography is a reliable method to
      objectively evaluate tumor thickness and surgical margin clearance.

PMID- 20031292
TI  - Deactivation in the sensorimotor area during observation of a human agent
      performing robotic actions.
AB  - It is well established that several motor areas, called the mirror-neuron system
      (MNS), are activated when an individual observes other's actions. However,
      whether the MNS responds similarly to robotic actions compared with human actions
      is still controversial. The present study investigated whether and how the motor
      area activity is influenced by appearance (human vs. robot) and/or kinematics
      (human vs. robot) of the observed action using near-infrared spectroscopy. The
      results showed that there was a strong interaction between these factors,
      revealing strong deactivations in sensorimotor areas when the subject saw a human
      agent performing robotic actions, which was significantly different from
      responses when observing the human agent acting in a human way and the robot
      agent performing robotic actions. These results indicate that MNS activity is
      sensitive to congruency between the appearance and kinematics of the agent,
      especially when the agent has a human appearance. We discuss the experience
      dependent characteristics of MNS sensitivity to observed actions.

PMID- 20031293
TI  - Cardoon allergy.

PMID- 20031294
TI  - Health burden of co-morbid asthma and allergic rhinitis in West Indian children.
AB  - BACKGROUND: Co-morbid allergic rhinitis (AR) and asthma has not been studied in
      Caribbean countries where there is a high prevalence of childhood asthma.
      METHODS: Using the International Primary Care Airways Group (IPAG) guidelines to
      determine AR, care-givers of 393 (response rate=100%) children attending asthma
      clinics in selected public sector health facilities in Trinidad, West Indies,
      were interviewed. RESULTS: Children (393) were between 2-17 years and included
      239 (60.8%) boys and 154 (39.2%) girls. As many as 53.9% of children sampled (95%
      CI 45.9-55.8) suffered from AR. Children exposed to household smoking were nearly
      twice as likely to have AR (p<0.0041, OR=1.9, CI 1.22-2.88). Significantly
      (p<0.01) more asthmatics with AR (154, 58.6%) visited Accident and Emergency
      (A&E) in the past 12 months. The odds of visiting A&E at least once in the past
      12 months for asthmatics with AR were 1.75 (95% CI 1.15-2.68). The average
      frequency of A&E visits was higher in children who also suffered from AR (1.75 vs
      1.36, p<0.04). Age was negatively correlated (-0.21, p<0.005) with exacerbation
      frequency for asthmatics without AR suggesting A&E visits are independent of age
      in co-morbid disease. More children with AR (>60%) suffer day and night symptoms
      (p<0.001), and miss school (59.8%) (p<0.03) at least once a week (p<0.002) than
      asthmatics without AR (OR=1.5, 95% CI=1.03-2.30). CONCLUSIONS: AR is prevalent in
      53.9% of Trinidadian children with asthma. The burden of co-morbid disease in
      asthmatic children is associated with increased likelihood of asthma-related A&E
      visits, day and night symptoms and absence from school.

PMID- 20031295
TI  - Horner's syndrome following epidural analgesia during labor: report of six cases.

PMID- 20031296
TI  - Evans' syndrome in pregnancy: a systematic literature review and two new cases.
AB  - Evans' syndrome, the coexistence of immune thrombocytopenia (ITP) with autoimmune
      haemolytic anaemia (AIHA), is rare in pregnancy, with a few published cases.
      Concerns about the teratogenic effect of pharmacological agents used in the
      management of Evans' syndrome limit the treatment options in pregnancy. In this
      paper we performed a systematic review of the literature of all published cases
      with Evans' syndrome in pregnancy and we report two new cases. The review was
      performed by searching the electronic databases PubMed, EMBASE, Cochrane Library
      and Google scholar up to the end of December 2008. The selection criteria were
      Evans' syndrome in pregnancy; autoimmune haemolytic anaemia; immune
      thrombocytopenia. Thirteen papers reporting 14 pregnancies in women with Evans'
      syndrome have been published: 7 papers are written in English. Evans' syndrome
      can be diagnosed with a full blood count, film and Coombs testing. It runs a more
      benign course in pregnancy than in non-pregnant state (notably neutropenia does
      not occur) and very often resolves post-delivery. The fetal outcome may be less
      favourable: a minority of fetuses are affected by transplacental passage of
      antibody and have a significant morbidity and mortality. With appropriate
      treatment, women with Evans' syndrome can have successful pregnancies, with a
      good response to conventional treatment. More detailed studies of Evans' syndrome
      in pregnancy, especially of fetal outcome, are required.

PMID- 20031297
TI  - A new approach to postoperative peritoneal adhesions: prevention of peritoneal
      trauma by aloe vera gel.
AB  - OBJECTIVE: Covering peritoneal surfaces with aloe vera gel may prevent peritoneal
      trauma and hence postoperative peritoneal adhesions. STUDY DESIGN: Forty Wistar
      albino out-bred female rats (mean weight, 180+/-25 g; mean age, 6 months) were
      divided into four groups. In Group 1, 0.1 mL aloe vera gel was injected into the
      peritoneal cavities. In Group 2, peritoneal adhesions were induced. In Group 3,
      adhesions were induced and the modeled area was covered by 0.1 mL aloe vera gel.
      In Group 4, the area was covered with aloe vera gel prior to adhesion induction.
      The rats were sacrificed on postoperative day 10 and the adhesions were scored
      both microscopically and macroscopically. RESULTS: The mean macroscopic adhesion
      score in the four groups was 0, 5.8+/-0.42, 5.2+/-0.79, and 1.1+/-1.2
      respectively, with the difference between Group 4 and Groups 2 (p<0.001) and 3
      (p<0.05) statistically significant. The mean histopathological fibrosis values
      were significantly higher in Group 3 than in Group 4 (2.6+/-0.51 vs 1.2+/-0.91,
      p=0.002). CONCLUSION: Aloe vera gel can effectively decrease adhesion formation
      if applied before, but not after, after peritoneal trauma. This effect is likely
      due not to its chemical properties but to its viscosity, providing a covering to
      prevent peritoneal trauma.

PMID- 20031298
TI  - Quantifying the membrane potential during E. coli growth stages.
AB  - The presence of the resting membrane potential has a strong effect on the
      dielectric behavior of cell suspensions. Using this observation and a well
      established theoretical model, the low frequency dielectric dispersion curves of
      E. coli cell suspensions are de-convoluted to obtain the resting membrane
      potential of E. coli cells at various growth stages. Four regions of the
      exponential growth stage are investigated and the measurements indicate that the
      membrane depolarizes from -220mV in the early exponential phase to -140mV in the
      late exponential phase. The conductivity of the cell suspension is also found to
      decrease as the cells progress from the early to the late exponential phases.

PMID- 20031299
TI  - Temporal variability of surface runoff due to cropping systems in cultivated
      catchment areas: Use of the DIAR model for the assessment of environmental public
      policies in the Pays de Caux (France).
AB  - This article proposes the use of a new model, DIAR (Diagnostic Agronomique du
      Ruissellement, or Agronomic Assessment of Runoff), for the prediction of the
      timing of the risk of runoff. DIAR is dedicated to loamy soils which are very
      sensitive to surface crusting, leading to runoff, soil erosion and muddy flows.
      The approach is proposed for the north-western European loess belt regions where
      muddy flows severely impact human activities. The likelihood of runoff is
      assessed from the sequence of soil surface states generated by cultivation
      practices. DIAR is based on the calculation of curve number values, for each
      stage of the soil-surface-state sequence, for calculating runoff for each of
      these stages. In this study, DIAR is applied to a catchment of 912 ha, cultivated
      by 26 farmers in the Pays de Caux (Normandy, France) where infrastructures
      located at the outlet have been damaged several times by muddy flows. Local
      public authorities involved in reducing muddy flows are eager to limit the
      agricultural upstream runoff by extending the planting of mustard as a winter
      cover crop. We tested the efficiency of such a policy on the reduction of the
      mean runoff. We also tested the year-to-year variability of this efficiency using
      the acreages of four successive years (1999-2000 to 2002-2003). Finally, the cost
      efficiency of the policy was also considered. Though we used the same weather
      scenario, the initial situation (without much mustard cover) showed a wide year
      to-year variation in the total runoff. This variation can be associated with the
      structure of the farms that cultivate the catchment (Utilised Agricultural Area
      (UAA) of each farm and percentage of this UAA inside the catchment). Our results
      showed that the widespread planting of winter cover crops could reduce the runoff
      by 10-20% compared with the initial situation (depending on the year), and also
      reduce the year-to-year variability of runoff. For each of the 4 tested years,
      the cost of the infiltrated m(3), due to each ha of mustard cover, decreases with
      the increase in mustard cover. It indicates that the present siting of the
      mustard cover is not as efficient as it could be. We should ask why farmers do
      not sow it elsewhere.

PMID- 20031300
TI  - Re: Umberto Capitanio, Shahrokh F. Shariat, Hendrik Isbarn, et al. Comparison of
      oncologic outcomes for open and laparoscopic nephroureterectomy: a multi
      institutional analysis of 1249 cases. Eur Urol 2009;56:1-9.

PMID- 20031301
TI  - Neurological complications of miliary tuberculosis.
AB  - INTRODUCTION: The symptomatic central nervous system involvement is often seen in
      patients with miliary tuberculosis. MATERIALS AND METHODS: In this study, we
      evaluated 60 consecutive miliary tuberculosis patients, who presented with some
      neurological manifestations. Evaluation included neurological examination, a
      battery of blood tests, HIV serology, sputum examination, cerebrospinal fluid
      (CSF) examination along with imaging of the brain and spinal cord. The patients
      were followed up after completion of 6 months of antituberculous treatment.
      RESULTS: Patients ranged between 14 and 53 years in age. Three patients tested
      HIV positive. Forty-eight (80%) patients had tuberculous meningitis. In 12 (20%)
      patients, the CSF examination was normal. In 27 patients with tuberculous
      meningitis, neuroimaging revealed intracerebral tuberculoma. Fourteen patients
      showed multiple tuberculomas, while 7 had a solitary tuberculoma. In six
      patients, the tuberculomas were small and numerous. In two patients, neuroimaging
      revealed a spinal tuberculoma. For three patients with tuberculous brain masses,
      the CSF was normal. Nine (15%) patients presented with myelopathy. Three patients
      exhibited Pott's paraplegia. Three patients had transverse myelitis (with normal
      neuroimaging). In three patients, the spinal MRI revealed an intramedullary
      tuberculoma. On follow-up, 15 (25%) patients expired. Thirty-one (52%) patients
      showed significant improvement. Eight patients (13%) showed nil or partial
      recovery. Six of the patients with no improvement developed vision loss. Six
      (10%) patients were lost to follow up. CONCLUSION: A variety of neurological
      complications were noted in military tuberculosis patients, tuberculous
      meningitis and cerebral tuberculomas being the most frequent complications.
      However, a majority of patients improved following antituberculous treatment.

PMID- 20031302
TI  - Cognitive forms of multiple sclerosis: report of a dementia case.
AB  - Cognitive impairment is now well documented in patients with multiple sclerosis
      (MS), and series of MS patients with predominant cognitive problems have been
      published recently. We report the observation of a female patient with severe
      cognitive presentation at the onset of MS, with dramatically demented evolution,
      and show MRI examination results. We discuss the published reports of primary
      cognitive types of MS.

PMID- 20031303
TI  - Intracranial plasmacytoma with apoplectic presentation and spontaneous
      intracerebral hemorrhage: Case report and review of the literature.
AB  - Involvement of the nervous system is not uncommon in patients with multiple
      myeloma, with polyneuropathy and myelopathy predominating. Intracranial
      involvement producing neurological symptoms, however, is distinctly uncommon.
      Massive intraparenchymal hemorrhage from a previously unrecognized intracranial
      plasmacytoma is exceedingly rare. The authors report the case of a 57-year-old
      male who presented with sudden onset of severe headache, rapid onset of right
      sided weakness and deterioration in level of consciousness while at work. Two
      years earlier the patient had completed treatment for multiple myeloma and was
      considered to be in remission, with a recent bone marrow biopsy that was
      negative, and complete normalization of serum protein electrophoresis. Imaging
      studies revealed a massive intracerebral hemorrhage with the possibility of an
      underlying lesion, and the patient was taken for emergent hematoma evacuation and
      tumor resection. The patient made an excellent recovery and was treated with
      intracranial radiation. Even in patients with multiple myeloma without evidence
      of systemic disease following successful treatment, the possibility of
      unrecognized lesions lingers. The onset of new symptoms referable to potential
      intracranial pathology in this setting should prompt consideration of
      intracranial plasmacytoma in the differential diagnosis.

PMID- 20031304
TI  - Motor and cognitive slowing in multiple sclerosis: an attentional deficit?
AB  - BACKGROUND: Action slowing is frequently observed in multiple sclerosis (MS)
      patients. Several factors may account for response slowing: motor, perceptual,
      cognitive deficits, global mental slowing. Our objective was to examine
      mechanisms accounting for action slowing in MS patients. METHODS: Twenty MS
      patients, free of visual impairment and of upper limbs sensory-motor deficit
      underwent previously validated reaction time (RT) tests using visual stimuli.
      Three tasks were used: (1) motor tapping, (2) simple reaction time (SRT) in a
      simple and dual task condition, and (3) choice RT (CRT) with varying response
      probabilities. Results were compared to those of 20 healthy matched subjects.
      RESULTS: MS patients had: (1) lower motor tapping frequency (p=0.02); (2) SRT
      lengthening (p=0.001) related to a lower proportion of fast responses (p=0.001)
      indicating attentional deficit whereas perceptuomotor index was spared (p=0.5),
      without higher sensitivity to dual task (p=0.9); and (3) CRT lengthening
      (p=0.001) with spared decision time (p=0.7). CONCLUSIONS: This study showed that
      action slowing of MS patient is mainly related to (1) attentional deficit
      resulting in inability to maintain high level of rapid actions, and (2) subtle
      motor slowing even in patients without motor deficit on clinical examination,
      whereas (3) divided attention and decisional process are preserved.

PMID- 20031305
TI  - Distribution of polycyclic aromatic hydrocarbons in different size fractions of
      soil from a coke oven plant and its relationship to organic carbon content.
AB  - The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in US EPA
      priority list were analyzed in the bulk and six particle size fractions of soil
      samples from a coke oven plant. The relationships of PAHs concentrations with
      total organic carbon (TOC), black carbon (BC) and other forms of organic carbon
      (OC) contents have been investigated. Total PAH concentrations ranged from 6.27
      to 40.18 mg kg(-1) dry weight. The highest total PAH concentration occurred in
      the 250-500 microm size fraction. The maximum individual PAH concentration was in
      the 250-500 microm or 500-2000 microm size fraction. The size fractions of 125
      500 microm and <50 microm have higher percentages and contributed 24.62% and
      23.33% of the total PAH mass, respectively. The relative abundance of individual
      PAH compounds and PAH molecular indices present typical characteristic pyrogenic
      origin. The maximal TOC and BC contents were found in the 125-250 microm size
      fraction. Strong positive linear relationship between total PAH concentration and
      TOC or BC has been demonstrated, with a linear regression coefficient value of
      0.7277 and 0.9245, respectively. The linear relationship between total PAH
      concentration versus OC (OC = TOC - BC) is weaker than that versus TOC or BC,
      with a correlation coefficient of 0.4117. It indicates that partitioned in
      organic matter, especially in black carbon is the dominant form of PAHs in the
      soil.

PMID- 20031306
TI  - Treatment of dye wastewater with permanganate oxidation and in situ formed
      manganese dioxides adsorption: cation blue as model pollutant.
AB  - This study investigated the process of potassium permanganate (KMnO(4)) oxidation
      and in situ formed hydrous manganese dioxides (deltaMnO(2)) (i.e., KMnO(4)
      oxidation and deltaMnO(2) adsorption) for the treatment of dye wastewater. The
      effectiveness of decolorization, removing dissolved organic carbon (DOC), and
      increasing biodegradable oxygen demand (BOD) were compared among these processes
      of KMnO(4) oxidation, deltaMnO(2) adsorption, and KMnO(4) oxidation and
      deltaMnO(2) adsorption. DeltaMnO(2) adsorption contributed to the maximum DOC
      removal of 65.0%, but exhibited limited capabilities of decolorizing and
      increasing biodegradability. KMnO(4) oxidation alone at pH 0.5 showed
      satisfactory decrease of UV-vis absorption peaks, and the maximum BOD(5)/DOC
      value of 1.67 was achieved. Unfortunately, the DOC removal was as low as 27.4%.
      Additionally, the great amount of acid for pH adjustment and the much too low pH
      levels limited its application in practice. KMnO(4) oxidation and deltaMnO(2)
      adsorption at pH 2.0 was the best strategy prior to biological process, in
      balancing the objectives of decolorization, DOC removal, and BOD increase. The
      optimum ratio of KMnO(4) dosage to X-GRL concentration (R(KMnO(4)/X-GRL)) was
      determined to be 2.5, at which KMnO(4) oxidation and deltaMnO(2) adsorption
      contributed to the maximal DOC removal of 53.4%. Additionally, the optimum pH for
      X-GRL treatment was observed to be near 3.0.

PMID- 20031307
TI  - The use of polyethyleneglycolmethacrylate-co-vinylimidazole (PEGMA-co-VI)
      microspheres for the removal of nickel(II) and chromium(VI) ions.
AB  - The polyethyleneglycolmethacrylate-co-vinylimidazole (PEGMA-VI) copolymers, that
      can be used in heavy metal removal applications, were synthesized and
      characterized; and their use as sorbents in heavy metal removal was investigated.
      It was determined that the ligand vinylimidazole was successfully inserted into
      the polymer structure. Then, chromium (Cr(VI)) and nickel (Ni(II)) ions were used
      as model species to investigate the usability of the obtained microspheres in
      heavy metal removal. The effects of pH of the adsorption medium, initial
      concentration of the metal ions and VI content of PEGMA-VI microspheres were
      investigated as the effective parameters on the adsorption capacities of the
      microspheres. The adsorption rate of the microspheres was also investigated for
      determination of the optimum adsorption time which is the required time for
      maximum adsorption capacity. The adsorption capacities under optimum conditions
      were also determined. The order of adsorption affinities of PEGMA-VI microspheres
      with respect to the used metals was determined by competitive adsorption studies.
      According to the obtained results, the highest adsorption affinity of the PEGMA
      VI microspheres was towards Cr(VI) ions, the adsorption affinity was less for
      Ni(II) and the least affinity was towards Cu(II) ions. The adsorption-desorption
      studies showed that the microspheres were reusable without a significant decrease
      in the ion adsorption capacities.

PMID- 20031308
TI  - Hybrid inorganic/organic alumina adsorbents-functionalized-purpurogallin for
      removal and preconcentration of Cr(III), Fe(III), Cu(II), Cd(II) and Pb(II) from
      underground water.
AB  - Metal pollution is well recognized as one of the major environmental problems
      that must be imperatively addressed and solved. In this study, three types of
      alumina adsorbents (I-III) were physically immobilized with purporogallin as a
      chelating ion exchangers. These were found to exhibit strong capability and
      selectivity characters for a series of heavy metal ions. Surface modification of
      hybrid alumina was characterized and identified from the determination of surface
      coverage and infrared analysis. Hybrid alumina adsorbents were identified for
      their strong resistivity to acid leaching in pH>2-7 as well as their high thermal
      stability up to 350 degrees C. The ability of newly synthesized hybrid
      inorganic/organic alumina adsorbents (I-III) to bind and extract various metal
      ions was examined and evaluated in various buffer solutions (pH 1.0-7.0) via
      determination of the metal adsorption capacity values. These were identified as
      high as 420-560, 500-580 and 500-590 micromol g(-1) for alumina adsorbents (I),
      (II) and (III), respectively in the case of high concentration levels of Cr(III),
      Fe(III) and Cu(II). The influence of alumina matrices were highly characterized
      when low concentration levels (microg ml(-1) and ng ml(-1)) of metal ions were
      used. Hybrid alumina adsorbents were successfully applied for selective
      extraction, removal and preconcentration of various heavy metals from underground
      water samples with percentage recovery values of 92-100+/-1-3%.

PMID- 20031309
TI  - Production of basic chromium sulfate by using recovered chromium from ashes of
      thermally treated leather.
AB  - Leather wastes tanned with chromium are generated during the production process
      of leather, hence the wastes from hand crafted goods and footwear industries are
      a serious environmental problem. The thermal treatment of leather wastes can be
      one of the treatment options because the wastes are rich in chromium and can be
      used as a raw material for sodium chromate production and further to obtain
      several chromium compounds. The objective of this study was to utilize the
      chromium from leather wastes via basic chromium sulfate production to be
      subsequently applied in a hide tanning. The obtained results have shown that this
      is the first successful attempt to achieve desired base properties of the
      product. The result was achieved when the following conditions were applied: a
      molar ratio between sodium sulfite and sodium dichromate equal to 6; reaction
      time equal to 5 min before addition of sulfuric acid; pH of sodium dichromate
      solution equal to 2. Summarizing, there is an opportunity to utilize the
      dangerous wastes and reused them in the production scheme by minimizing or
      annulling the environmental impact and to attend a sustainable process
      development concept.

PMID- 20031310
TI  - Assessment of arsenic toxicity using Allium/Vicia root tip micronucleus assays.
AB  - Arsenic is ubiquitous in the environment and is a potential human carcinogen. Its
      carcinogenicity has been demonstrated in several models. In this study, broad
      bean (Vicia faba L.) and common onion (Allium cepa L.), two plant species which
      are commonly used for detecting the genotoxic effects of environmental
      pollutants, were used to measure possible genotoxic effect of arsenite (0.3-30
      mg/l). Present results showed that arsenite (As(III)) induced micronuclei (MN)
      formation in both Allium and Vicia root tips. MN frequency significantly
      increased in Vicia root cells exposed to 0.3-10 mg/l arsenite and in Allium root
      cells exposed to 1-30 mg/l arsenite, which indicated that Vicia root tip cells
      are more sensitive to arsenite than Allium. Mitotic index (MI) decreased in a
      concentration-dependent manner and showed significant differences in Vicia/Allium
      roots among treatments and the control, after exposure to 1-30 mg/l arsenite for
      at least 4 h. In the present study, MN frequency was positively associated with
      lipid peroxidation, which indicated that arsenite exposure can induce oxidative
      stress, cytotoxicity and genotoxicity in plant cells. The results also suggested
      that Vicia/Allium root micronucleus (MN) assays are simple, efficient and
      reproducible methods for the genotoxicity monitoring of arsenic water
      contamination.

PMID- 20031311
TI  - Removal of insecticide carbofuran from aqueous solutions by banana stalks
      activated carbon.
AB  - In this work, activated carbon was prepared from banana stalks (BSAC) waste to
      remove the insecticide carbofuran from aqueous solutions. The effects of contact
      time, initial carbofuran concentration, solution pH and temperature (30, 40 and
      50 degrees C) were investigated. Adsorption isotherm, kinetics and thermodynamics
      of carbofuran on BSAC were studied. Equilibrium data were fitted to the Langmuir,
      Freundlich and Temkin isotherm models and the data best represented by the
      Langmuir isotherm. Thermodynamic parameters such as standard enthalpy
      (DeltaH(o)), standard entropy (DeltaS(o)) and standard free energy (DeltaG(o))
      were evaluated. Regeneration efficiency of spent BSAC was studied using ethanol
      as a solvent. The efficiency was found to be in the range of 96.97-97.35%. The
      results indicated that the BSAC has good regeneration and reusability
      characteristics and can be used as alternative to present commercial activated
      carbon.

PMID- 20031312
TI  - Enhanced toluene removal using granular activated carbon and a yeast strain
      Candida tropicalis in bubble-column bioreactors.
AB  - The yeast strain Candida tropicalis was used for the biodegradation of gaseous
      toluene. Toluene was effectively treated by a liquid culture of C. tropicalis in
      a bubble-column bioreactor, and the toluene removal efficiency increased with
      decreasing gas flow rate. However, toluene mass transfer from the gas-to-liquid
      phase was a major limitation for the uptake of toluene by C. tropicalis. The
      toluene removal efficiency was enhanced when granular activated carbon (GAC) was
      added as a fluidized material. The GAC fluidized bioreactor demonstrated toluene
      removal efficiencies ranging from 50 to 82% when the inlet toluene loading was
      varied between 13.1 and 26.9 g/m(3)/h. The yield value of C. tropicalis ranged
      from 0.11 to 0.21 g-biomass/g-toluene, which was substantially lower than yield
      values for bacteria reported in the literature. The maximum elimination capacity
      determined in the GAC fluidized bioreactor was 172 g/m(3)/h at a toluene loading
      of 291 g/m(3)/h. Transient loading experiments revealed that approximately 50% of
      the toluene introduced was initially adsorbed onto the GAC during an increased
      loading period, and then slowly desorbed and became available to the yeast
      culture. Hence, the fluidized GAC mediated in improving the gas-to-liquid mass
      transfer of toluene, resulting in a high toluene removal capacity. Consequently,
      the GAC bubble-column bioreactor using the culture of C. tropicalis can be
      successfully applied for the removal of gaseous toluene.

PMID- 20031313
TI  - Multivariate statistical analysis of heavy metals pollution in industrial area
      and its comparison with relatively less polluted area: a case study from the City
      of Peshawar and district Dir Lower.
AB  - Multivariate and univariate statistical techniques i.e., cluster analysis PCA,
      regression and correlation analysis, one way ANOVA, were applied to the metal
      data of effluents soil and ground water to point out the contribution of
      different industries towards the metals pollution, their source identification
      and distribution. The samples were collected from different industries and
      different downstream points of the main effluents stream and from the relatively
      less polluted area considered as control area. The samples were analyzed for
      metal concentration levels by flame atomic absorption spectrophotometer. The
      metal concentration data in the three media of the polluted area were compared
      with background data and control data as well as with the WHO safe limits. The
      results showed that soil has high metals concentration compared to effluents and
      water. The data also showed elevated levels of Mn and Pb in water that are 8.268
      and 2.971 mg/L, respectively. Principal component analysis along with regression
      analysis showed that the elevated levels of metals in the effluents contaminate
      adjacent soil and ultimately the ground water. The other elements Co, Cd, Ni and
      Cu were also found to have correlation in the three media.

PMID- 20031314
TI  - Hexachlorobenzene dechlorination by indigenous sediment microorganisms.
AB  - Indigenous microbes from the sediments, whether contaminated with
      hexachlorobenzene (HCB) or not, could dechlorinate HCB effectively without any
      acclimation and supplemental nourishment. Temperature seriously affected the HCB
      dechlorination: within the measured 15-45 degrees C span, the optimum range was
      between 30 and 35 degrees C. Sulfate-reducing bacteria (SRB), denitrifiers, and
      acetogens might not be directly involved in the HCB dechlorination. However, the
      SRB retarded subsequent dechlorination of pentachlorobenzene to tetra- and
      trichlorobenzenes. Some vancomycin-resistant gram-positive bacteria and
      methanogens were most likely to be the HCB-dechlorinators. The dechlorination
      followed the Michaelis-Menten behavior with the k'(m) and K(HCB) between 0.45
      0.73 mg L(-1)day(-1) and 3.2-17.2 mg L(-1), respectively. These findings suggest
      a potential HCB treatment and cleanup for wastewater and contaminated site.

PMID- 20031315
TI  - Interaction of cadmium and zinc in biological samples of smokers and chewing
      tobacco female mouth cancer patients.
AB  - Epidemiologic studies suggest that zinc (Zn) deficiency and high accumulation of
      cadmium (Cd) may be associated with increased risk of cancer. The incidence of
      mouth cancer has increased among females, who possess habits of chewing tobacco
      with gradients (areca nut and betel quid) and smoking tobacco in Pakistan. In
      present study, we measured the concentration of Cd and Zn in 96 mouth cancer
      patients (MCPs) and 110 female controls/referents (67 smoker and chewing
      tobacco), while 43 have none of smoking and chewing tobacco habits, belongs to
      different cities of Pakistan. Both controls and patients have same age group
      (ranged 35-65 years), socio-economic status, localities and dietary habits. The
      Zn and Cd were determined by flame/graphite furnace atomic absorption
      spectrophotometer, prior to microwave assisted acid digestion method. The Cd/Zn
      ratio in both biological samples was also calculated. The results of this study
      showed that the mean value of Zn was lower, while the mean concentration of Cd
      was higher in the blood and scalp hair samples of MCPs as compared to control
      subjects (p<0.001). The controls chewing and smoking tobacco have high level of
      Cd in both biological samples as compared to those have not smoking or chewing
      tobacco (p<0.012). The Cd/Zn ratio was higher in MCPs than control subjects. This
      study is compelling evidence in support of positive associations between cadmium,
      cigarette smoking, deficiency of Zn and cancer risk.

PMID- 20031316
TI  - Laboratory investigation of DNAPL migration in porous media.
AB  - Laboratory experiments have been carried out with and without groundwater flow in
      a two-dimensional laboratory-scale tank to assess the influence of layered media
      and hydraulic gradient on DNAPL infiltration and redistribution processes.
      Hydrofluoroether has been used as DNAPL and glass beads have been utilized as
      porous medium. An image analysis procedure has been used to determine saturation
      distribution during infiltration and redistribution processes. This method allows
      quantitative time dependent full fields mapping of the DNAPL saturation, as well
      as the monitoring of DNAPL saturation variation. By means of performed
      experiments important information were obtained about the migration and
      redistribution process, the infiltration and migration velocity, the
      characteristics of migration body. The experimental results show that the
      hydraulic gradient promotes the infiltration process, increasing the infiltration
      rate. It hampers DNAPL spread and fingering bringing to a reduction of residual
      DNAPL and it also promotes the DNAPL redistribution, and it reduces the amount
      remaining at residual saturation. Furthermore the hydraulic gradient promotes
      downward and down-gradient migration. DNAPL migration in the direction of water
      flow, can be considered important due to significant errors in the location of
      sources in the case of high gradients and high aquifer thicknesses, and for high
      water flow velocities, such as those which can be expected during pumping actions
      in water supply or in remediation activities.

PMID- 20031317
TI  - Effects of the presence of a composted biosolid on the metal immobilizing action
      of an urban soil.
AB  - The influence of a composted biosolid from urban wastewater treatment on the
      retention and solubility of Cu, Pb or Zn added to a soil was studied by batch
      adsorption/desorption experiments, equilibrating both materials and their
      mixtures with solutions containing various metal concentrations. The composted
      biosolid adsorbed less Cu or Pb and slightly more Zn than the soil, and thus
      caused a noticeable decrease in the retention of Cu or Pb and an increase in Zn
      adsorption by soil-biosolid mixtures, but these effects in the mixtures were not
      additive for any metal. The pH effects were studied by means of (log metal
      concentration)/pH diagrams. It was shown that Cu behaviour was different from
      that of the other metals: the relation between pH and Cu concentrations suggested
      similar solubilities in the presence of the biosolid and the mixtures, whereas
      the biosolid-free soil gave data located on a region of the diagram corresponding
      to slightly lower solubility. In the case of Pb or Zn, the data for the biosolid
      were located in a region of the diagram corresponding to clearly lower
      solubilities than those for the biosolid/soil mixtures. It was concluded that the
      biosolid has little effect on metal solubility when it is mixed with the soil in
      the proportions used here.

PMID- 20031318
TI  - Cr(VI) reduction in wastewater using a bimetallic galvanic reactor.
AB  - The electrochemical reduction of Cr(VI)-Cr(III) in wastewater by iron and copper
      iron bimetallic plates was evaluated and optimized. Iron has been used as a
      reducing agent, but in this work a copper-iron galvanic system in the form of
      bimetallic plates is applied to reducing hexavalent chromium. The optimal pH (2)
      and ratio of copper to iron surface areas (3.5:1) were determined in batch
      studies, achieving a 100% reduction in about 25 min. The Cr(VI) reduction
      kinetics for the bimetallic system fit a first order mechanism with a correlation
      of 0.9935. Thermodynamic analysis shows that the Cr(VI) reduction is possible at
      any pH value. However, at pH values above 3.0 for iron and 5.5 for chromium
      insoluble species appear, indicating that the reaction will be hindered.
      Continuous column studies indicate that the bimetallic copper-iron galvanic
      system has a reduction capacity of 9.5890 mg Cr(VI) cm(-2) iron, whereas iron
      alone only has a capacity of 0.1269 mg Cr(VI) cm(-2). The bimetallic copper-iron
      galvanic system is much more effective in reducing hexavalent chromium than iron
      alone. The exhausted plates were analyzed by SEM, EDS, and XRD to determine the
      mechanism and the surface effects, especially surface fouling.

PMID- 20031319
TI  - BBQ charcoal combustion as an important source of trace metal exposure to humans.
AB  - To provide information about charcoal combustion as an important source of
      atmospheric trace metal pollution, 11 charcoal products were combusted and PM(10)
      filter samples were collected. The PM-bound metal elements were extracted by
      microwave acid digestion and analyzed by ICP-AES. The concentrations of trace
      metal elements ranged from a few to 10(5)ng m(-3) in the following order of
      magnitude: Zn>Pb>Mg>Ba>Cu>V>Cr>Co>Cd>Ni>Mn>Se>As. Emissions of most elements from
      charcoal combustion were high compared to other sources. In case of Cd, Co, and
      Ni, their concentrations exceeded the inhalation minimum risk levels (MRLs) of
      the United States Agency for Toxic Substances and Disease Registry (US-ATSDR) for
      chronic duration exposure by a factor of 30, 3.9, and 2.2, respectively.
      Likewise, Cd levels exceeded the US-ATSDR MRLs for acute-duration exposure by a
      factor of 10, while those of Pb and Cd exceeded air quality guideline (AQG) of
      the World Health Organization (WHO) by a factor of 29 and 59, respectively. Mn
      levels also exceeded the United States Environmental Protection Agency (US EPA)
      Reference Air Concentrations (RfCs) by a factor of 2.7. This study shows that
      barbecue charcoal combustion can be an important source of trace metal emissions
      to the atmosphere with potential health risks.

PMID- 20031320
TI  - Degradation of the drug sodium diclofenac by Trametes versicolor pellets and
      identification of some intermediates by NMR.
AB  - Degradation of diclofenac sodium, a nonsteroidal anti-inflammatory drug widely
      found in the aquatic environment, was assessed using the white-rot fungus
      Trametes versicolor. Almost complete diclofenac removal (> or = 94%) occurred the
      first hour with T. versicolor pellets when the drug was added at relatively high
      (10 mg L(-1)) and environmentally relevant low (45 microg L(-1)) concentrations
      in a defined liquid medium. In vivo and in vitro experiments using the cytochrome
      P450 inhibitor 1-aminobenzotriazole and purified laccase, respectively, suggested
      at least two different mechanisms employed by T. versicolor to initiate
      diclofenac degradation. Two hydroxylated metabolites, 4'-hydroxydiclofenac and 5
      hydroxydiclofenac, were structurally elucidated by nuclear magnetic resonance as
      degradation intermediates in fungal cultures spiked with diclofenac. Both parent
      compound and intermediates disappeared after 24 h leading to a decrease in
      ecotoxicity calculated by the Microtox test. Laccase-catalyzed transformation of
      diclofenac led to the formation of 4-(2,6-dichlorophenylamino)-1,3
      benzenedimethanol, which was not detected in in vivo experiments probably due to
      the low laccase activity levels observed through the first hours of incubation.

PMID- 20031326
TI  - Identification of novel and zoonotic Cryptosporidium species in marine fish.
AB  - Little is known about the prevalence and genotypes of Cryptosporidium in fish.
      The present study investigated the prevalence of Cryptosporidium species in
      cultured fingerlings (n=227), wild freshwater (n=227) and wild marine/estuarine
      species (n=255) of fish in Western Australia by PCR amplification at the 18S rRNA
      locus. Results revealed a low prevalence of Cryptosporidium infection in fish
      hosts; 0.8% (6/709). Four species of Cryptosporidium were identified including C.
      parvum, C. xiaoi and pig genotype II in whiting (Sillago vittata) and a novel
      Cryptosporidium spp. in mullets (Mugil cephalus). The identification of zoonotic
      species of Cryptosporidium in fish indicates that future research to gain a
      better understanding of the public health impacts is warranted. The detection of
      the protozoa in fish may also be a good sentinel for environmental contamination
      or ecosystem health.

PMID- 20031321
TI  - Nociceptive sensitization by complement C5a and C3a in mouse.
AB  - Activation of the complement system by injury increases inflammation by producing
      complement fragments C5a and C3a which are able to recruit and activate immune
      cells. Complement activation may contribute to pain after inflammation and
      injury. In this study, we examined whether C5a and C3a elicit nociception when
      injected into mouse hind paws in vivo, and whether C5a and C3a activate and/or
      sensitize mechanosensitive nociceptors when applied on peripheral terminals in
      vitro. We also examined the dorsal root ganglia (DRG) for C5a receptor (C5aR)
      mRNA and effects of C5a and C3a on intracellular Ca(2+) concentration
      ([Ca(2+)](i)) using Ca(2+) imaging. Heat hyperalgesia was elicited by
      intraplantar injection of C5a, and mechanical hyperalgesia by C5a and C3a. After
      exposure to either C5a or C3a, C-nociceptors were sensitized to heat as evidenced
      by an increased proportion of heat responsive fibers, lowered response threshold
      to heat and increased action potentials during and after heat stimulation. A
      nociceptors were activated by complement. However, no change was observed in
      mechanical responses of A- and C-nociceptors after C5a and C3a application. The
      presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated
      [Ca(2+)](i) and facilitated capsaicin-induced [Ca(2+)](i) responses in DRG
      neurons. The results suggest a potential role for complement fragments C5a and
      C3a in nociception by activating and sensitizing cutaneous nociceptors.

PMID- 20031327
TI  - Recovery of Toxocara canis eggs from soil.

PMID- 20031328
TI  - Development and evaluation of real-time PCR assays for the quantitative detection
      of Babesia caballi and Theileria equi infections in horses from South Africa.
AB  - A quantitative real-time polymerase chain reaction (qPCR) assay using a TaqMan
      minor groove binder (MGB) probe was developed for the detection of Babesia
      caballi infection in equids from South Africa. Nine previously published
      sequences of the V4 hypervariable region of the B. caballi 18S rRNA gene were
      used to design primers and probes to target unique, conserved regions. The B.
      caballi TaqMan MGB qPCR assay was shown to be efficient and specific. The
      detection limit, defined as the concentration at which 95% of positive samples
      can be detected, was determined to be 0.000114% parasitized erythrocytes (PE). We
      further evaluated a previously reported Theileria equi-specific qPCR assay and
      showed that it was able to detect the 12 T. equi 18S rRNA sequence variants
      previously identified in South Africa. Both qPCR assays were tested on samples
      from two ponies experimentally infected with either T. equi or B. caballi. The
      qPCR assays were more sensitive than the indirect fluorescent antibody test
      (IFAT) and the reverse-line blot (RLB) during the early onset of the disease. The
      assays were subsequently tested on field samples collected from 41 horses,
      resident on three stud farms in the Northern Cape Province, South Africa. The
      IFAT detected circulating T. equi and B. caballi antibody in, respectively, 83%
      and 70% of the samples. The RLB detected T. equi parasite DNA in 73% of the
      samples, but none of the samples were positive for B. caballi, although 19 T.
      equi-positive samples also hybridized to the Babesia genus-specific probe. This
      could indicate a mixed T. equi and B. caballi infection in these samples, with
      either the B. caballi parasitaemia at a level below the detection limit of the B.
      caballi RLB probe, or the occurrence of a novel Babesia genotype or species. In
      contrast, the qPCR assays correlated fairly well with the IFAT. The B. caballi
      TaqMan MGB qPCR assay was able to detect B. caballi parasite DNA in 78% of the
      samples. The T. equi-specific qPCR assay could positively detect T. equi DNA in
      80% of the samples. These results suggest that the qPCR assays are more sensitive
      than the RLB assay for the detection of T. equi and B. caballi infections in
      field samples.

PMID- 20031329
TI  - Intestinal helminths of feral cat populations from urban and suburban districts
      of Qatar.
AB  - A survey of the helminths of 658 adult cats from feral urban and suburban
      populations in Qatar was conducted across all months in 2006 and 2007. Six
      species of helminths were identified, comprising two cestodes (Taenia
      taeniaeformis [73.6%] and Diplopylidium acanthotetra [47.1%]) and four nematodes
      (Ancylostoma tubaeforme [14.7%], Physaloptera praeputialis [5.2%], Toxocara cati
      [0.8%] and Toxascaris leonina [0.2%]), and 83% of cats were infected with at
      least one of these. The average number of species harboured was 1.4 and the
      average worm burden was 55.8 worms/cat. The vast majority of worms (97.6%) were
      cestodes, nematodes being relatively rare. Prevalence and abundance of infections
      were analyzed, taking into consideration four factors: year (2006 and 2007), site
      (urban and suburban), season (winter and summer) and sex of the host. Analyses
      revealed marked year effects, female host bias in some species and interactions
      involving combination of factors, but especially sex and season of the year. The
      results indicate that whilst the majority of adult feral cats in Qatar carry
      helminth infections, infections are variable between years and subject to annual
      changes that may reflect climatic and other environmental changes in the rapidly
      developing city of Doha and its suburban surroundings. Only two species have the
      potential to infect humans and both were rare among the sampled cats (A.
      tubaeforme and T. cati).

PMID- 20031330
TI  - Emerging trends in the seroprevalence of canine leishmaniasis in the Madrid
      region (central Spain).
AB  - This report describes a cross-sectional serological survey of the epidemiology of
      canine leishmaniasis (CanL) performed in 2006 and 2007 in the Madrid region
      (central Spain) where the disease is endemic. The work presented here is one of
      the several studies conducted in different Spanish regions under the Integrated
      Project of the European Commission entitled Emerging Diseases in a changing
      European eNvironment (EDEN). The aim of this project is to identify and catalogue
      European ecosystems and environmental conditions that determine the spatial and
      temporal distributions and dynamics of several pathogenic agents including
      Leishmania infantum (EDEN-LEI). The study area (Madrid Autonomous Region) was
      selected on the grounds of its wide altitude range. This area was surveyed from
      NE to SW across its mountain range (Sistema Central) and plateau area. One
      thousand and seventy-six dogs from 32 villages were examined for clinical signs
      of CanL, and serum samples were obtained to determine several haematological and
      biochemical variables. Leishmaniasis-specific antibodies were identified using an
      indirect immunofluorescence antibody test (IFAT). 87 of the 1076 dogs were
      seropositive for the protozoan (IFAT: cut-off>or=1/80) indicating a
      seroprevalence of 8.1% (0-16.1% depending on the village). On the basis of a
      physical examination and the biochemical/haematological status of each dog, 32 of
      the 87 infected dogs were described as clinically healthy (37%). Seroprevalence
      showed a peak in young dogs (1-2 years) and a second larger peak among the older
      dogs (7-8 years). Factors correlated with a higher infection risk were age
      (OR=1.15 [95% CI: 1.07-1.22]), weight (OR=1.10 [95% CI: 1.04-1.16]), and living
      outdoors as opposed to in a home (OR=3.38 [95% CI: 1.42-8.05]). According to data
      from studies performed in 1992 in the same area, the seroprevalence of CanL has
      increased 1.54-fold [95% CI: 1.04-2.29]. Given that this increasing trend cannot
      be attributed to differences in the sociodemographic characteristics of the dog
      populations, it is proposed that environmental changes could have had an impact
      on vector and reservoir densities and their geographical distributions. Further
      studies designed to explain this trend should attempt to correlate sand fly
      densities and CanL seroprevalences with climate, land use and human changes.

PMID- 20031331
TI  - An integrated clinical approach for the identification, prevention, and treatment
      of tumor lysis syndrome.
AB  - Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder
      that occurs when tumor cells undergo rapid decomposition spontaneously or in
      response to cytoreductive therapy. Delayed recognition of the metabolic
      imbalances caused by the massive release of tumor cell contents may result in
      clinical complications such as acute kidney injury, seizures, and cardiac
      arrhythmias. Prevention, the key principle in TLS management, relies on the
      identification of patients at risk for developing TLS during chemotherapy or
      because of disease progression. TLS-related risk factors pertain to tumor type
      (particularly hematologic malignancies), specific tumor characteristics (e.g.
      bulky tumor, high cellular proliferation rate, sensitivity to cytoreductive
      therapy), and other host-related factors. A comprehensive grading system proposed
      by Cairo and Bishop classifies TLS syndromes into laboratory or clinical TLS,
      thus facilitating TLS prevention and management. The mainstays of TLS management
      include monitoring of electrolyte abnormalities, vigorous hydration, prophylactic
      antihyperuricemic therapy with allopurinol, and rasburicase treatment of patients
      at high TLS risk or with established hyperuricemia. Urine alkalinization and use
      of diuretics remain controversial clinical practices. In this review, we describe
      the incidence of, risk factors for, and diagnostic characteristics of TLS and
      summarize strategies for the prevention and management of TLS-associated
      metabolic abnormalities, particularly hyperuricemia. We specifically highlight
      recently published TLS management guidelines, which focus on the prevention of
      TLS and hyperuricemia based on a patient's level of risk, and the important role
      of nephrologists in the prevention and treatment of one of the most serious
      complications of TLS, acute kidney injury.

PMID- 20031332
TI  - Approach to radiation therapy in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), the 5th most common cancer and the third most
      common cause of cancer-related death in the world with an estimated incidence of
      approximately 1 million new cases annually, has becoming a major global health
      problem in the world. A variety of treatment modalities, including resection,
      liver transplantation, transarterial chemoembolization (TACE), local ablative
      therapy and radiation therapy (RT) have been reported. Although partial
      hepatectomy and liver transplantation may offer the best chance of cure, only 15%
      of the patients have the chance to be treated by surgery when diagnosed. The
      effectiveness of systemic chemotherapy for HCC has been minimal, and local
      ablative therapy may offer comparable survival in patients with small HCC and
      preserve liver function. Recently, with developments in radiotherapy techniques,
      radiotherapy has been shown to play potential roles in a wide spectrum of HCC and
      to become more important so that it is necessary to evaluate the effect of
      radiotherapy in treatment of HCC. This paper is aiming mainly at the current
      radiation therapy strategies and their current advances, the optimal radiation
      therapy strategies will complement the current treatments and improve the
      treatment efficiency.

PMID- 20031333
TI  - Depression and anxiety: Associations with biological and perceived stress
      reactivity to a psychological stress protocol in a middle-aged population.
AB  - BACKGROUND: Depression and anxiety have been linked to higher as well as lower
      reactivity to stressful circumstances. Large, population-based studies
      investigating the association between depression and anxiety, perceived and
      physiological stress responses are lacking. METHODS: We studied 725 men and
      women, aged 55-60 years, from a population-based cohort, who filled out the
      Hospital Anxiety and Depression Scale (HADS). We performed a standardized
      interview on medical history and lifestyle. We measured continuous blood pressure
      (BP) and heart rate (HR) reactivity, saliva cortisol reactivity and perceived
      stress during a psychological stress protocol. RESULTS: Albeit not statistically
      significant in all groups, systolic BP (SBP), diastolic BP (DBP), HR and cortisol
      reactivity to the psychological stress protocol were lower in those with mild-to
      severe depression or anxiety symptoms and those ever clinically diagnosed with
      depression or anxiety, while perceived levels of stress were higher compared to
      those without depression or anxiety symptomatology. Maximum SBP, HR and cortisol
      stress responses significantly decreased and perceived stress scores
      significantly increased with increasing scores on the HADS depression subscale
      (HADS-D) and HADS anxiety subscale (HADS-A) (all P<0.05). The same held for
      stress responses in relation to the total HADS score (all P<0.05) and, in this
      case, the maximum DBP stress response was also significantly lower with an
      increasing HADS score (P=0.05). In addition, the maximum DBP stress response was
      significantly lower for those ever clinically diagnosed with depression (P=0.04).
      Adjusting for sex, use of anti-hypertensive medication, anti-depressant and
      anxiolytic medication, smoking, alcohol consumption, socio-economic status (SES)
      and body mass index (BMI) did not attenuate the results. CONCLUSION: The present
      study results suggest that the biological stress response of middle-aged men and
      women who experienced depressed and anxious feelings does not completely
      correspond with how stressed they feel at that moment. Although differences were
      not substantial in all cases, response to a psychological stress protocol seemed
      to be decreased in the groups with experience of depressed and anxious feelings,
      while the perception of stress seemed to be increased.

PMID- 20031334
TI  - Can traditional "cupping" treatment cause a stroke?
AB  - The case study of a patient who developed haemorrhagic stroke after 'cupping' to
      the cervical area is presented. We consider the various manners in which cupping
      might induce haemorrhagic or ischemic stroke with particular reference to the
      relevant pathologies of the major cervical arteries. The other possible causes
      due to the induced cupping stresses are also examined using a computer based
      simulation study. Cupping of the cervical area may cause a haemorrhagic stroke by
      an acute rise in blood pressure. The tensile radial stresses generated by cupping
      may potentially facilitate the development of a dissection in the presence of an
      intimal tear. Moreover, the possible presence of micro-inclusions can intensify
      the local stress concentration for a thin cap.

PMID- 20031335
TI  - Scope of medical implications of the Master Development Program hypothesis.

PMID- 20031336
TI  - Hypotheses concerning rickettsial microorganisms, autoimmune diseases and new
      treatment strategies.

PMID- 20031337
TI  - Is the increase in LDL cholesterol induced by selective serotonin reuptake
      inhibitor therapy a blessing in disguise?

PMID- 20031338
TI  - Targeting hematogenous spread of circulating tumor cells by a chemotactic drug
      eluting IVC filter to prevent pulmonary and systemic metastasis.
AB  - The formation of distant metastases is the main cause of morbidity and mortality
      in patients with cancer. Hematogenous spread through venous drainage of tumors is
      the main route of metastatic spread. We propose that the use of a drug-eluting
      chemotactic Inferior vena cava (IVC) filter coated with specific antibodies to
      surface markers of circulating tumor cells will attract these malignant cells and
      lyse them thus theoretically decreasing formation of distant systemic metastases.
      This could have a major impact on cancer related morbidity and mortality caused
      by metastatic disease.

PMID- 20031339
TI  - [Reply to the remarks on the article HELLP syndrome-like by vitamin B12
      deficiency: report of seven cases].

PMID- 20031340
TI  - Maillard reaction, mitochondria and oxidative stress: potential role of
      antioxidants.
AB  - Glycation and oxidative stress are two important processes known to play a key
      role in complications of many disease processes. Oxidative stress, either via
      increasing reactive oxygen species (ROS), or by depleting the antioxidants may
      modulate the genesis of early glycated proteins in vivo. Maillard Reactions,
      occur in vivo as well as in vitro and are associated with the chronic
      complications of diabetes, aging and age-related diseases. Hyperglycaemia causes
      the autoxidation of glucose, glycation of proteins, and the activation of polyol
      metabolism. These changes facilitate the generation of reactive oxygen species
      and decrease the activity of antioxidant enzymes such as Cu,Zn-superoxide
      dismutase, resulting in a remarkable increase of oxidative stress. A large body
      of evidence indicates that mitochondria alteration is involved and plays a
      central role in various oxidative stress-related diseases. The damaged
      mitochondria produce more ROS (increase oxidative stress) and less ATP (cellular
      energy) than normal mitochondria. As they are damaged, they cannot burn or use
      glucose or lipid and cannot provide cell with ATP. Further, glucose, amino acids
      and lipid will not be correctly used and will accumulate outside the
      mitochondria; they will undergo more glycation (as observed in diabetes, obesity,
      HIV infection and lipodystrophia). The objective of this paper is to discuss how
      to stop the vicious circle established between oxidative stress, Maillard
      Reaction and mitochondria. The potential application of some antioxidants to
      reduce glycation phenomenon and to increase the antioxidant defence system by
      targeting mitochondria will be discussed. Food and pharmaceutical companies share
      the same challenge, they must act now, urgently and energetically.

PMID- 20031341
TI  - Salvia divinorum: effects and use among YouTube users.
AB  - Salvia divinorum (salvia) is an intense, short-acting hallucinogenic plant
      gaining popularity among adolescents in the United States. There has been little
      scientific documentation of salvia's effects. The popular video-sharing website
      YouTube has received literally thousands of video-posts of people using salvia.
      The objective of this study was to assess the effects of salvia use through
      systematic observations of YouTube videos. A sample of salvia videos was obtained
      using the search term "salvia." The videos were further screened and only videos
      that captured the entire drug "trip" without video edits were included in the
      analyses described here (n=34). Three trained research assistants independently
      watched the videos and rated their observations on 42 effects in 30-s intervals.
      Onset of symptoms was quick (often less than 30s) and tended to dissipate within
      8min. Further, there was a relationship between salvia dose and effect duration.
      Since salvia's effects on humans are largely undocumented, this study provides
      the look at users in a non-laboratory environment (e.g. self-taped videos)
      exhibiting impairments and behaviors consistent with this powerful hallucinogen.
      Also, this study demonstrates the feasibility and shortcomings of using YouTube
      videos to assess emerging drugs and drug effects.

PMID- 20031342
TI  - Porcine Torque teno virus: determination of viral genomic loads by genogroup
      specific multiplex rt-PCR, detection of frequent multiple infections with
      genogroups 1 or 2, and establishment of viral full-length sequences.
AB  - Torque teno virus (TTV) is a non-enveloped virus with a circular, single-stranded
      DNA genome. TTV is currently classified in the unassigned genus Anellovirus, and
      distinct TTVs of tentative species-status infect a wide range of vertebrates. In
      domestic pigs and wild boars, porcine TTV occurs in two genogroups, TTV1 and
      TTV2, which are currently detected using only conventional PCR assays. To allow
      high-throughput testing, the present study describes development of a multiplex
      real-time (rt)-PCR assay for efficient simultaneous detection of TTV1 and TTV2.
      To demonstrate usefulness of this rt-PCR assay for large-scale testing, 203 serum
      samples from domestic pigs were screened for TTV infection. The detected rates of
      single TTV1, single TTV2, and double TTV1/TTV2 infections were 32, 17, and 32%
      and represent the first report on the occurrence of porcine TTV in Germany. In
      addition, 100 wild boar lung samples were tested that confirmed high prevalences
      of TTV infection. Moreover, establishment of genogroup-specific rt-PCR standards
      allowed the determination of mean viral genomic loads in sera from TTV-infected
      swine to about 10(4.5)/ml, respectively. To verify the specificity of the rt-PCR
      assay, conventional PCR assays that amplify genogroup-specific, size
      distinguishable products from the TTV untranslated regions were designed. In
      total, 50 clones derived from 24 PCR products obtained from 19 TTV1 and TTV2
      single- or double-infected animals were sequenced. Phylogenetic analyses of these
      sequences demonstrated the frequent occurrence of multiple infections with
      distinct porcine TTVs of the same genogroup. Moreover, two porcine TTV full
      length sequences were established, one for each genogroup.

PMID- 20031343
TI  - Immunization of pregnant sows with a novel virulence gene deleted live Salmonella
      vaccine and protection of their suckling piglets against salmonellosis.
AB  - This study was carried out to examine a novel Salmonella Typhimurium (S.
      Typhimurium) vaccine for protection of suckling piglets against salmonellosis by
      immunization of pregnant sows using various administration routes. The vaccine
      strain was constructed by deletion of cpxR and lon from a wild type S.
      Typhimurium and the S. Typhimurium Delta cpxR Delta lon Delta asd secreting the B
      subunit of the Escherichia coli heat-labile enterotoxin were used as a live form
      of mucosal adjuvant for this study. Pregnant sows were divided into 4 groups of 3
      sows a piece. Sows were primed at 8 weeks of pregnancy and were boosted 11 weeks
      of pregnancy. Group A sows were primed intramuscularly with the formalin
      inactivated vaccine and boosted orally with the live vaccine and mucosal
      adjuvant, group B sows were orally primed with the live vaccine and mucosal
      adjuvant and boosted orally with live vaccine, group C sows were orally primed
      with live vaccine and mucosal adjuvant and intramuscularly boosted, and group D
      sows were primed and boosted with phosphate-buffered saline as controls. Piglets
      were orally challenged with a virulent S. Typhimurium strain at day 6 after
      birth. Sows from group A and B had significantly increased IgG levels compared to
      control group sows (P<0.05), and group C sows had lower IgG levels compared to
      group A and B sows. Mucosal sIgA and IgG levels in group A and B sow colostrums
      were significantly increased as compared to those of group D sows (P<0.05). Serum
      IgG and IgA levels in group A and B piglets were also significantly increased as
      compared to those of group D piglets (P<0.001). These data suggested that
      systemic and mucosal immune responses were highly induced by the vaccine
      candidate, especially when this was administered by both routes of intramuscular
      prime and oral booster, and oral prime and booster. Furthermore, clinical signs
      such as diarrhea and weight loss were not observed after virulent Salmonella
      strain challenge in group A and B suckling piglets, however, group C (41.7%) and
      group D (83.3%) piglets suffered from diarrhea. This data suggested that sow
      immunized by intramuscular-prime and oral booster and oral prime and oral booster
      with this vaccine candidate effectively protected piglets from salmonellosis.

PMID- 20031344
TI  - Proportion of the litter farrowed, litter size, and progesterone and estradiol
      effects on piglet birth intervals and stillbirths.
AB  - Stillbirth in swine ranges from 2 to 9%, resulting in a significant loss of
      piglets. Previous studies clearly indicate a relationship between prolonged birth
      intervals and stillbirth, but factors influencing birth intervals are not fully
      known. To characterize birth intervals and stillbirth, farrowing was recorded
      during three farrowing seasons. Blood samples were collected on d 110 and d 113
      of gestation, and were assayed for progesterone and estrogen. Relationships
      between estrumate (cloprostenol sodium, an analogue of prostaglandin F(2alpha))
      usage, litter size, proportion of the litter farrowed, progesterone and estrogen
      concentrations, birth intervals, and stillbirth were analyzed using regression
      analysis. A clear relationship between birth intervals and stillbirth was
      observed. Stillbirth rate was unaffected by birth intervals of <1 h, and
      increased (P < 0.01) for birth intervals >1 h. A significant negative association
      between litter size and birth intervals was observed (P < 0.01). Birth intervals
      were unaffected by proportion of the litter farrowed until the last piglet in the
      litter, whose birth interval increased dramatically (1.5-fold; P < 0.01).
      Stillbirth rates increased as proportion of the litter farrowed increased, and a
      dramatic increase in stillbirth occurred for the last piglet in the litter.
      Neither d 110 nor 113 plasma progesterone concentrations were associated with
      litter size, birth intervals, or stillbirth rates. Curvilinear relationships were
      present between d 110 or 113 plasma estradiol concentrations and litter size.
      However, neither d 110 nor 113 estradiol concentrations were associated with
      birth intervals or stillbirth rates. These results indicate that (1) birth
      intervals greater than 1 h are associated with increased stillbirth; (2) larger
      litter size reduces birth intervals; (3) the last piglet in the litter has both a
      prolonged birth interval and increased risk of stillbirth; (4) plasma
      progesterone before farrowing does not influence birth intervals or stillbirth;
      and (5) plasma estradiol does not influence birth interval or stillbirth, despite
      a positive relationship between litter size and plasma estradiol. An
      understanding of the effects of litter size and proportion of the litter farrowed
      on birth intervals might be exploited to decrease stillbirth in piglets.

PMID- 20031345
TI  - Menopause and modifiable coronary heart disease risk factors: a population based
      study.
AB  - OBJECTIVES: The aim of our study was to determine the effect of the menopause on
      various coronary heart disease (CHD) risk factors and on the global risk of CHD
      in a population based sample of women, making the difference between menopause
      and age related effects. STUDY DESIGN: The Third French MONICA cross-sectional
      survey on cardiovascular risk included 1730 randomly selected women, aged 35-64
      years, representative from the general population. MAIN OUTCOME MEASURES: Women
      were defined as post-menopausal (postM; n=696), peri-menopausal (periM; n=183) or
      pre-menopausal (preM; n=659) based on the date of last menses. Socio-demographic,
      clinical and biological data were collected. Analyses of variance were used to
      compare means. RESULTS: PostM women had significantly higher age-adjusted levels
      of total cholesterol (6.0mmol/L in postM vs. 5.7mmol/L in preM, p<0.05) and LDL
      cholesterol (3.9mmol/L vs. 3.6mmol/L, p<0.05). There was no difference in HDL
      cholesterol or triglyceride levels, glycemia or blood pressure. Further
      adjustment on body mass index and hormonal treatments did not modify the results.
      No risk factor was significantly different between periM and postM. However, the
      Framingham 10-year risk of CHD was higher in postM, as compared with periM (5.1%
      vs. 5.0%, p<0.05). In postM women, lipids and the Framingham risk were not
      associated with elapsed time since menopause. CONCLUSIONS: The CHD risk increases
      during the sixth decade could be explained not only by estrogen deprivation but
      also by an effect on lipid profile, which is likely to occur in the peri
      menopause period.

PMID- 20031346
TI  - Menopausal hormone therapy and risk of lung cancer-Systematic review and meta
      analysis.
AB  - OBJECTIVES: Lung cancer rates increase among women in many regions of the world.
      To explore whether menopausal hormone therapy (MHT) plays a role. METHODS: We
      conducted a systematic search of the literature and performed meta-analyses of
      cohort studies (C), case-control studies (CC), randomized controlled trials
      (RCTs), and cancer registry studies (CR) to analyse the impact of estrogen
      therapy (ET), estrogen/progestin therapy (EPT) and any hormone therapy (HT) on
      lung cancer risks. We explored associations between ever-use of therapies and
      risks, analysed annual changes of risk, and the impact of therapies on
      histological subtypes. We calculated summary odds ratios, relative risks, 95%
      confidence intervals (CI; fixed-effects model), and assessed heterogeneity across
      studies. Eighteen studies were eligible (9 CC, 4 C, 3 RCT, 2 CR). RESULTS: We
      found a significant increase of risk - 76.2% - in non-smoking women with
      adenocarcinoma (CI 1.072-2.898) reporting ever-use of HT. Estrogen plus progestin
      therapy does not change the risk; however, the pooled analysis of 2 RCTs points
      at an increased risk (RR 1.359; CI 1.031-1.791). Our further results should be
      interpreted with caution as significances were found in analyses only when
      smoking and non-smoking women, various hormone regimens, or histological
      subtypes, respectively, were pooled. CONCLUSIONS: Dedicated studies designed to
      more adequately delineate the role of MHT are necessary to substantiate whether
      use of MHT is a risk factor for this or other types of lung cancer.

PMID- 20031347
TI  - Treatment of menopausal hot flashes with 5-hydroxytryptophan.
AB  - OBJECTIVE: Much recent research has focused on nonhormonal treatments for
      menopausal hot flashes. The purpose of the present study was to determine the
      effects of 5-hydroxytroptophan (5-HTP), the immediate precursor of serotonin,
      upon menopausal hot flashes. Selective, serotonergic, reuptake inhibitors
      (SSRIs), which increase the amount of serotonin in the synaptic gap, have shown
      some promise in the amelioration of hot flashes. METHODS: We administered 5-HTP
      or placebo, in double-blind fashion, to 24 postmenopausal women reporting
      frequent hot flashes. Treatment outcome was measured using a miniature,
      electronic, hot flash recorder. RESULTS: No significant effects of 150 mg/day 5
      HTP upon hot flash frequency were found. The 5-HTP group had 23.8 + or - 5.7 (SD)
      hot flashes/24 h prior to treatment and 18.5 + or - 9.6 at the end of treatment.
      The placebo group had 18.5 + or - 9.6 before treatment and 22.6 + or - 12.4 at
      treatment completion. CONCLUSIONS: At the dose given, 5-HTP does not
      significantly ameliorate frequency of menopausal hot flashes, as measured
      objectively with an electronic recorder. Given the small size, this study must be
      considered preliminary in nature.

PMID- 20031348
TI  - Levels of vitamin D and cardiometabolic disorders: systematic review and meta
      analysis.
AB  - Cardiometabolic disorders and vitamin D deficiency are becoming increasingly more
      prevalent across multiple populations. Different studies have suggested a
      potential association between abnormal vitamin D levels and multiple pathological
      conditions including cardiovascular diseases and diabetes. We aimed to evaluate
      the association between vitamin D levels, using 25-hydroxy vitamin D (25OHD) as
      an indicator of vitamin D status, and the presence of cardiometabolic disorders
      including cardiovascular disease, diabetes and metabolic syndrome. We performed a
      systematic review of the current literature on vitamin D and cardiometabolic
      disorders using the PubMed and Web of Knowledge databases in September 2009.
      Studies in adults looking at the effect of vitamin D levels on outcomes relating
      to cardiometabolic disorders were selected. We performed a meta-analysis to
      assess the risk of developing cardiometabolic disorders comparing the highest and
      lowest groups of serum 25OHD. From 6130 references we identified 28 studies that
      met our inclusion criteria, including 99,745 participants. There was moderate
      variation between the studies in their grouping of 25OHD levels, design and
      analytical approach. We found that the highest levels of serum 25OHD were
      associated with a 43% reduction in cardiometabolic disorders [OR 0.57, 95% (CI
      0.48-0.68)]. Similar levels were observed, irrespective of the individual
      cardiometabolic outcome evaluated or study design. High levels of vitamin D among
      middle-age and elderly populations are associated with a substantial decrease in
      cardiovascular disease, type 2 diabetes and metabolic syndrome. If the
      relationship proves to be causal, interventions targeting vitamin D deficiency in
      adult populations could potentially slow the current epidemics of cardiometabolic
      disorders.

PMID- 20031349
TI  - The metabolic syndrome: validity and utility of clinical definitions for
      cardiovascular disease and diabetes risk prediction.
AB  - The purpose of clinical definitions of the metabolic syndrome is frequently
      misunderstood. While the metabolic syndrome as a physiological process describes
      a clustering of numerous age-related metabolic abnormalities that together
      increase the risk for cardiovascular disease and type 2 diabetes, clinical
      definitions include obesity which is thought to be a cause rather than a
      consequence of metabolic disturbance, and several elements that are routinely
      measured in clinical practice, including high blood pressure, high blood glucose
      and dyslipidaemia. Obesity is frequently a central player in the development of
      the metabolic syndrome and should be considered a key component of clinical
      definitions. Previous clinical definitions have differed in the priority given to
      obesity. Perhaps more importantly than its role in a clinical definition,
      however, is obesity in isolation before the hallmarks of metabolic dysfunction
      that typify the syndrome have developed. This should be treated seriously as an
      opportunity to prevent the consequences of the global diabetes epidemic now
      apparent. Clinical definitions were designed to identify a population at high
      lifetime CVD and type 2 diabetes risk, but in the absence of several major risk
      factors for each condition, are not optimal risk prediction devices for either.
      Despite this, the metabolic syndrome has several properties that make it a useful
      construct, in conjunction with short-term risk prediction algorithms and sound
      clinical judgement, for the identification of those at high lifetime risk of CVD
      and diabetes. A recently published consensus definition provides some much needed
      clarity about what a clinical definition entails. Even this, however, remains a
      work in progress until more evidence becomes available, particularly in the area
      of ethnicity-specific waist cut-points.

PMID- 20031350
TI  - Risk factors related to the presence and severity of hot flushes in mid-aged
      Ecuadorian women.
AB  - BACKGROUND: Several studies drawn from the Ecuadorian population have previously
      reported that more than half of mid-aged women present hot flushes, which can
      impair their quality of life. However up-to-date risk factors for their presence
      and severity have not been assessed. OBJECTIVE: To assess hot flush frequency and
      intensity and related risk factors among middle-aged Ecuadorian women. METHODS:
      In this cross-sectional study, 1154 healthy women aged 40-59 years, visiting
      healthcare centers of eight main cities of Ecuador with more than 100,000
      inhabitants, were assessed with the first item of the Menopause Rating Scale
      (MRS) and a questionnaire containing female and partner socio-demographic data.
      RESULTS: Mean age of the entire sample was 48.8+/-5.6 years (median 48), a 48.7%
      had 12 or less years of schooling, 52.8% were postmenopausal, 43.6% lived at high
      altitude, 56.8% were married and 10% were on hormonal therapy (HT). Hot flushes
      accounted for 56% (n=646) of the whole sample, of which 29.1% and 9.1% were
      respectively graded as severe and very severe. Logistic regression determined
      that female sedentarism (OR: 2.42, CI 95% [1.63-3.59]), accessing a free
      healthcare system (OR: 1.96, CI 95% [1.30-2.96]), living at high altitude (OR:
      1.82, CI 95% [1.14-2.90]) and having a partner abusing alcohol (OR: 1.92, CI 95%
      [1.09-3.35]) were significant risk factors related to the presence of hot
      flushes. The regression model also determined that among women with hot flushes
      (n=646), sedentarism (OR: 1.73, CI 95% [1.14-2.62]) and having a partner with
      erectile dysfunction (OR: 2.57, CI 95% [1.44-4.59]) were significant risk factors
      related to severe/very severe hot flushes whereas married status (OR: 0.53, CI
      95% [0.32-0.86]), living at high altitude (OR: 0.46, CI 95% [0.26-0.78]) and
      partner healthiness (OR: 0.59, CI 95% [0.36-0.95]) were not. CONCLUSION: To the
      best of our knowledge this is the first and largest study assessing hot flushes
      in a mid-aged Ecuadorian population. We found that the presence and severity were
      not significantly related to age and hormonal status yet to other individual
      female/male characteristics and the demography of the studied population.

PMID- 20031351
TI  - DNA degradation and genetic analysis of empty puparia: genetic identification
      limits in forensic entomology.
AB  - Puparial cases are common remnants of necrophagous flies in crime investigations.
      They usually represent the longest developmental time and, therefore, they can be
      very useful for the estimation of the post-mortem interval (PMI). However, before
      any PMI estimate, it is crucial to identify the species of fly eclosed from each
      puparium associated with the corpse. Morphological characteristics of the
      puparium are often distinctive enough to permit a species identification. But,
      even an accurate morphological analysis of empty puparia cannot discriminate
      among different species of closely related flies. Furthermore, morphological
      identification may be impossible if the fly puparia are poorly preserved or in
      fragments. This study explores the applicability of biomolecular techniques on
      empty puparia and their fragments for identification purposes. A total of 63
      empty puparia of necrophagous Diptera resulting from forensic casework were
      examined. Samples were divided into three groups according to size, type and time
      of eclosion in order to verify whether the physical characteristics and puparia
      weathering can influence the amount of DNA extraction. The results suggest that a
      reliable genetic identification of forensically important flies may also be
      performed from empty puparia and/or their fragments. However, DNA degradation can
      deeply compromise the genetic analysis since the older the fly puparia, the
      smaller are the amplified fragments.

PMID- 20031352
TI  - Modified fronto-lateral laryngectomy in treatment of glottic T1(a-b) cancer with
      anterior commissure involvement.
AB  - OBJECTIVE: Evaluation of clinical and oncological safety of the modified fronto
      lateral laryngectomy in the treatment of T1a-b glottic cancer. METHODS:
      Retrospective review of charts of patients managed with classical fronto-lateral
      laryngectomy or with our modified technique using a cervical fascia flap and a
      false cord flap to reconstruct the defect. RESULTS: No recurrence of cancer was
      observed in the present series and slight dysphonia was present in all cases. The
      patients managed with classical technique required a revision surgery for
      granulations or anterior synechia in 4 cases; those managed with modified
      technique did not need a second intervention. CONCLUSION: The fronto-lateral
      laryngectomy should be present in the head-neck surgeon armamentarium. In T1a-b
      glottic cancer this technique gives a good oncological resection, but the
      postoperative period requires an intensive rehabilitation process. The
      modification of the classical technique reduces the incidence of a second
      intervention.

PMID- 20031353
TI  - A case of idiopathic lymph leakage in the neck.
AB  - A 48-year-old female patient was seen in our institution complaining of sudden
      onset of swelling and tenderness in the left side of her neck. Computed
      tomography and magnetic resonance imaging revealed abundant effusions in this
      area. Since these narrowed the patient's airway, we performed incisional drainage
      and intra-operatively we observed a transparent, colorless lymph fluid that oozed
      from the operative field, which was mainly a fatty layer at the supraclavicular
      area. Dilated lymphatic ducts were seen along the carotid artery and internal
      jugular vein, but damaged lymphatic ducts and obvious causative disease
      structures like tumorous lesions were not seen. Idiopathic lymph leakage was
      diagnosed due to the serous discharge from the left side of the neck and no
      apparent causative disease. The patient was successfully treated with incisional
      drainage and dietary restriction. Lymph leakage in the neck is more common after
      trauma or surgery. To our knowledge, no similar cases have ever been reported.

PMID- 20031354
TI  - Change of the human taste bud volume over time.
AB  - OBJECTIVE: The specific aim of this study is to measure the taste volume in
      healthy human subjects over a 2.5-month period and to demonstrate morphological
      changes of the peripheral taste organs. MATERIAL AND METHODS: Eighteen human
      taste buds in four fungiform papillae (fPap) were examined over a 10-week period.
      The fungiform papillae investigated were selected based on the form of the
      papillae or the arrangement of surface taste pores. Measurements were performed
      over 10 consecutive weeks, with five scans in a day once a week. The following
      parameters were measured: height and diameter of the taste bud, diameter of the
      fungiform papilla and diameter of the taste pore. RESULTS: The findings of this
      exploratory study indicated that (1) taste bud volumes changed over a 10-week
      period, (2) the interval between two volume maxima within the 10-week period was
      3-5 weeks, and (3) the diameter of the fPap did not correlate with the volume of
      a single taste bud or with the volume of all taste buds in the fPap within the 10
      week period. CONCLUSIONS: This exploratory in vivo study revealed changes in
      taste bud volumes in healthy humans with age-related gustatory sensitivity. These
      findings need to be considered when studying the effect of denervation of
      fungiform papillae in vivo using confocal microscopy.

PMID- 20031355
TI  - Transoral laser microsurgery for recurrence after primary radiotherapy of early
      glottic cancer.
AB  - OBJECTIVE: To analyze oncological results of transoral laser microsurgery (TLM)
      on recurrent early glottic cancer after primary radiotherapy. METHODS: The
      records of 53 patients treated by TLM for early (rTis-rT2) and advanced (rT3,
      rT4) recurrence after curative radiotherapy were retrospectively analyzed. Data
      on loco-regional control, overall survival, and disease specific survival were
      calculated by the Kaplan-Meier method. The larynx preservation rates were given
      absolutely. RESULTS: Mean post-therapeutic follow-up time after TLM for patients
      alive was 87.9 months. Twenty-two patients (42%) were cured by the first TLM
      procedure, but one of them underwent total laryngectomy after TLM due to
      chondronecrosis without evidence of residual tumor. Thirty-one patients (58%)
      developed another recurrence after TLM. Ten of them were cured by further laser
      procedures alone. Therefore, in 31 patients (58%), local recurrences were
      successfully treated by TLM alone. In 20 patients, recurrences could not be
      controlled by TLM: 14 patients underwent salvage laryngectomy and six palliative
      treatment. Three- and five-year loco-regional control rates for all patients were
      46.1 and 38.8%. Three- and five-year overall survival rates were 67.5 and 53.3%.
      The corresponding 3- and 5-year disease specific survival rates were 68.6%, each.
      There was no statistically significant difference in loco-regional control or
      survival between patients presenting initially with early and advanced
      recurrence. Further recurrence after the first TLM procedure was associated with
      a statistically significant decrease in 3- and 5-year overall (56.6% vs. 81.8%
      and 40.2% vs. 70.5%; p=0.03) and disease specific (48.9% vs. 100%, each; p=0.001)
      survival. Ultimate local control rate including repeated TLM and salvage
      laryngectomy was 77.4%. CONCLUSIONS: Many patients with recurrent glottic
      carcinoma after primary radiotherapy can be cured by single or repeated TLM as an
      organ-preserving procedure. However, in case of failure after TLM for the first
      recurrence, salvage laryngectomy should be considered early as local control by
      further laser surgery is unfavorable.

PMID- 20031356
TI  - Identification and characterization of novel sequence variations in MECP2 gene in
      Rett syndrome patients.
AB  - Rett syndrome (RS) is a neurodevelopmental disorder caused by mutations in MECP2
      gene. Exons 2, 3, and 4, in addition to intronic and 3'UTR adjacent regions, were
      sequenced in 80 patients with RS. Twenty-nine sequence variations were detected
      in 49 patients, 34 (69.4%) patients with the classic form of RS, and 15 (30.6%)
      patients with atypical forms of RS. Thirteen of the 29 detected mutations
      represent novel sequence variations. Missense mutation T158M was the most
      commonly observed mutation, detected in nine patients (11.2%). Six hotspot
      pathogenic mutations (R133C, T158M, R168X, R255X, R270X, and R294X) were
      responsible for the phenotype in 26/80 patients (32.5%).

PMID- 20031357
TI  - Tau proteins in the cerebrospinal fluid of patients with subacute sclerosing
      panencephalitis.
AB  - Neurodegenerative diseases characterized by cytoskeletal deformation and
      neurofibrillary tangles are associated with altered levels of tau and related
      proteins in cerebrospinal fluid (CSF). Neuronal or glial fibrillary tangles have
      been shown in 20% of subacute sclerosing panencephalitis (SSPE) patients. We
      therefore investigated CSF samples from 60 newly diagnosed SSPE and 31
      neurological control patients for total tau (t-tau), phosphorylated tau (p-tau),
      and S100-B levels by ELISA. There was no difference between patient and control
      groups in t-tau and S100-B levels. p-Tau was lower in the SSPE group (p=0.009).
      Past history of measles infection, measles immunization status, latent period
      between measles and onset of SSPE, duration of symptoms, frequency of myoclonia,
      neurological deficit index, stage and progression rate of the disease, CSF
      glucose levels and cell counts, CSF and serum measles IgG titer, distribution of
      lesions on brain magnetic resonance imaging were not related to t-tau, p-tau and
      S100-B levels. Mental status and age were negatively correlated with t-tau, and
      male gender and EEG abnormalities were associated with higher t-tau levels. The
      levels of tau proteins in our patients suggest there is no, or only scarce and
      immature, neurofibrillary tangle formation in SSPE. Autopsy studies showing
      neurofibrillary tangles might have examined older patients with longer disease
      and more parenchymal involvement.

PMID- 20031358
TI  - Carotid artery stenosis quantification: concordance analysis between radiologist
      and semi-automatic computer software by using Multi-Detector-Row CT angiography.
AB  - PURPOSE: Carotid artery stenosis quantification is still considered a leading
      parameter in the choice of the therapeutic option. Our purpose was to asses the
      concordance between radiologist and a semi-automatic computer software in the
      stenosis quantification of carotid artery studied by using a Multi-Detector-Row
      CT angiography (MDCTA). METHODS AND MATERIAL: 45 patients studied by using a 40
      detector row CT scanner were retrospectively analyzed. Carotid artery stenosis
      was quantified by one high experienced radiologist in vessel analysis and by
      using a dedicated software. Carotid artery stenosis was calculated according to
      the ECST method. Bland-Altman statistics was used to measure the inter- and intra
      concordance between radiologist and software and correlation coefficient between
      measures were performed by using nonparametric Spearmann correlation statistic. A
      p value<0.05 was considered to mean statistical significance. RESULTS: A strength
      correlation according to linear regression (correlation Spearman'rho
      coefficient=0.975; p<0.0001) between radiologist and software of vessel analysis
      was observed. Between first and second stenosis of carotid artery quantification
      performed by radiologist and software of vessel analysis we observed a
      Spearman'rho coefficient=0.943 (p<0.0001) and a Spearman'rho coefficient=0.9879;
      (p<0.0001) respectively. CONCLUSIONS: Our results indicated that there is a
      strength correlation according to linear regression between stenosis of carotid
      artery quantification performed by radiologist and semi-automatic software.
      Reproducibility between measurements performed by semi-automatic software are
      higher compared to radiologist.

PMID- 20031359
TI  - Relationship between levels of serum creatinine and perirenal hyperintensity on
      heavily T2-weighted MR images.
AB  - OBJECTIVE: To determine the frequency of perirenal hyperintensity on heavily T2
      weighted images and to evaluate its relationship with serum creatinine levels.
      SUBJECTS AND METHODS: Axial and coronal single-shot fast spin-echo images which
      have been originally obtained for MR cholangiopancreatography in 150 subjects
      were examined by two observers individually for the presence of perirenal
      hyperintensity. The morphologic properties of perirenal hyperintensity
      (peripheral rim-like, discontinuous, polar) were recorded. Chi square test was
      used to test whether the frequencies of bilateral perirenal hyperintensity differ
      significantly in subjects with high serum creatinine levels and those with normal
      creatinine levels. This test was also used to compare the frequencies of
      perirenal hyperintensity in patients with and without renal cysts and in patients
      with and without corticomedullary differentiation. A p value of less than 0.05
      was considered to be statistically significant. RESULTS: The perirenal
      hyperintensity was identified in 40 of 150 cases (26.6%) on heavily T2-weighted
      image. Serum creatinine levels were high in 18 of 150 cases (12%). The perirenal
      hyperintensity was present in 11 of 18 subjects (61%) with high serum creatinine
      levels and 26 of 132 subjects (19.7%) with normal creatinine levels. The
      difference of rates in two groups was statistically significant. Odds ratio was
      6407 (95% confidence interval 2264 -18,129) . The frequency of perirenal
      hyperintensity was also significantly higher in subjects with renal cyst or cysts
      in whom serum creatinine levels were normal (p<0.05) (37.5% vs. 11.8%).
      CONCLUSION: Perirenal hyperintensities are more frequent in patients with high
      serum creatinine levels. They are also more common in patients with simple renal
      cysts.

PMID- 20031360
TI  - The value teleradiology represents for Europe: a study of lessons learned in the
      U.S.
AB  - Pathology and demography have combined to fuel exponential demand for advanced
      medical imaging. To support this demand, radiology must move beyond traditional
      department or modality-based picture archiving and communication systems (PACS)
      to solutions that ensure access regardless of location. This article delineates
      underlying reasons for the growth in demand for access to medical imaging in both
      Europe and the United States. It explains why teleradiology/PACS is critical to
      support this growth in Europe. It discusses the benefits of and barriers to its
      widespread implementation as discovered in Canada and the U.S. and how these
      lessons learned relate to Europe. The article establishes the technological
      imperatives for teleradiology/PACS and presents three real-world case studies of
      successful data sharing and shared workflow models via single imaging
      implementations. Finally, it provides a high-level list of selection criteria for
      teleradiology/PACS and examines how industry trends affecting the U.S. are
      important baseline considerations to the success of teleradiology/PACS in Europe.

PMID- 20031361
TI  - Analytical approaches for the detection of epoxides and hydroperoxides in active
      pharmaceutical ingredients, drug products and herbals.
AB  - This review summarizes the analytical approaches reported in the literature
      relating to epoxide and hydroperoxide impurities. It is intended that it should
      provide guidance for analysts faced by the need to control such impurities,
      particularly where this is due to concerns relating to their potential
      genotoxicity. An extensive search of the literature relating to this class of
      impurities revealed a large number of references relating to analysis of
      epoxides/hydroperoxides associated with herbal remedies. Given the general
      applicability of the analytical methodology and due to the widespread use of
      herbal products the authors decided to include herbal medicines in this review.
      The review also reflects on the very different approaches taken in terms of the
      assessment/control of genotoxic impurities for such herbal remedies to that
      required for pharmaceutical products.

PMID- 20031362
TI  - Development and validation of an ion chromatography method for the determination
      of phosphate-binding of lanthanum carbonate.
AB  - Lanthanum carbonate is indicated to reduce serum phosphate in patients with end
      stage renal disease (ESRD). When given orally, lanthanum carbonate dissociates in
      the acid environment of the upper gastrointestinal tract to release lanthanum
      ions. The free lanthanum ions bind with dietary phosphate released from food
      during digestion to form highly insoluble lanthanum-phosphate complexes which
      prevent the absorption of phosphate, consequently reduce the serum phosphate. In
      order to evaluate the in vitro binding capacity of lanthanum carbonate, a simple
      and efficient ion chromatography (IC) method was developed and validated for
      determination of phosphate across the pH range encountered in the
      gastrointestinal tract. Chromatographic separation was achieved on a Dionex ICS
      2000 IC system using a Dionex AS16, IonPac (4mmx250mm) analytical column and
      Dionex AG16, IonPac (4mmx50mm) guard column. Column temperature was maintained at
      30 degrees C. Injection volume was 10microL. The compounds were eluted
      isocratically at a flow rate of 1mL/min and detected by suppressed conductivity.
      The analytical method was validated according to USP Category I requirements. The
      validation characteristics included accuracy, precision, quantification limit,
      linearity, and stability. The intra-day accuracy ranged from 89% to 103% for the
      solutions of pH 1.2-6.8. The intra-day precision (RSD) ranged from 0.6% to 3.7%
      for the solutions of pH 1.2-6.8. The analytical range was linear from 2 to 200ppm
      (mg/L). The R(2) ranged from 0.9998 to 1.0. This method was found to be simple,
      robust, sensitive, specific, and accurate. It has been successfully applied for
      determination of phosphate binding to lanthanum carbonate over the human
      gastrointestinal pH range at different time-points (from 0.5 to 24h).

PMID- 20031363
TI  - Quantification of the major metabolites of bromhexine in human plasma using RRLC
      MS/MS and its application to pharmacokinetics.
AB  - (E)-4-hydroxydemethylbromhexine (E-4-HDMB) and (E)-3-hydroxydemethylbromhexine (E
      3-HDMB) were found as major metabolites, while (Z)-4-hydroxydemethylbromhexine
      and (Z)-3-hydroxydemethylbromhexine as minor metabolites of bromhexine in human
      plasma. These compounds were identified in comparison with synthetic authentic
      samples. A sensitive and selective rapid resolution liquid chromatography tandem
      mass spectrometry (RRLC-MS/MS) method was developed to quantify the concentration
      of bromhexine and its two major metabolites (E-4-HDMB and E-3-HDMB) in human
      plasma. Following solid phase extraction, the analytes were separated on a Zorbax
      1.8microm particle size reversed-phase C(18) column, using a gradient elution
      program with solvents consisting of 0.1% formic acid in acetonitrile and 0.1%
      formic acid in 5mM ammonium acetate at a flow rate of 0.7mL/min. Detection was
      carried out with an Agilent 6460 triple-quadrupole mass spectrometer operated
      with an electrospray ionization source mode operated in the positive ion mode.
      The recovery of bromhexine, E-4-HDMB, E-3-HDMB, and internal standard (IS) was
      63.1-70.9%, 60.5-68.4%, 57.0-63.5%, and 87.8%, respectively. The matrix factors
      of bromhexine, E-4-HDMB, E-3-HDMB, and IS were 89.9-96.7%, 89.6-94.8%, 90.4
      91.4%, and 103%, respectively. After an oral administration of 8.0mg bromhexine
      to five healthy male subjects, AUC(0-24h) values of bromhexine, E-4-HDMB, and E-3
      HDMB were found to be 93.5+/-31.9, 34.0+/-14.5, and 15.8+/-6.89ngh/mL,
      respectively; while C(max) values were 24.6+/-5.16, 3.11+/-1.13, and 5.36+/
      2.55ng/mL, respectively. Plasma concentration of bromhexine, E-4-HDMB, and E-3
      HDMB declined with t(1/2) which gave 3.6+/-0.5, 8.4+/-2.7, and 6.4+/-2.5h,
      respectively.

PMID- 20031364
TI  - A tangential gunshot wound to the head: case report and review of the literature.
AB  - BACKGROUND: Patients with tangential gunshot wounds (TGSWs) commonly present with
      a good Glasgow Coma Scale score and without a history of loss of consciousness.
      Typically, the bullet does not breach the skull, however, there is a considerable
      force directed into the brain, and these patients are best treated as sustaining
      a moderate-to-severe blunt head injury. These patients require observation and
      repeat imaging. Physicians should be aware of this entity as these patients can
      deteriorate in a delayed fashion. OBJECTIVES: The authors present a case of a
      TGSW to the head in a neurologically intact patient. The initial post-injury
      computed tomography (CT) scan showed a very small subdural hematoma (SDH) with no
      overlying fracture of the skull. A delayed CT scan performed 4 h after arrival to
      the Emergency Department and 6 h after injury demonstrated an increase in size of
      the SDH, new traumatic subarachnoid hemorrhage, and bilateral cerebral
      contusions. Clinically, the patient showed worsening of her neurological
      examination. She underwent aggressive non-surgical treatment for increased
      intracranial pressure with almost complete recovery. CONCLUSION: Although
      patients with TGSWs are typically in good condition upon presentation, these
      injuries are not always trivial, and these patients should have, at minimum, a
      non-contrast brain CT scan to evaluate underlying damage to the brain and skull.
      In addition, a delayed CT scan and close observation on a neurosurgical service
      are indicated.

PMID- 20031365
TI  - Cerebral venous sinus thrombosis in the emergency department: retrospective
      analysis of 17 cases and review of the literature.
AB  - BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare but serious cause
      of neurologic impairment. Due to its relative rarity, there is limited research
      that describes the incidence and clinical features of CVST in the emergency
      department (ED). OBJECTIVES: To describe the demographic, clinical, and
      historical characteristics of patients with CVST who were initially seen in the
      ED. METHODS: This is a retrospective analysis of all patients presenting to three
      urban, tertiary care hospitals between January 2001 and December 2005 who were
      diagnosed with CVST. Patients were excluded if they were transferred from other
      hospitals, or admitted directly to the hospital without evaluation in the ED. We
      use one representative case to describe the presentation, evaluation, and
      treatment of CVST. RESULTS: Seventeen patients met the inclusion criteria.
      Patients had a mean age of 42 years. Presenting complaints included headache
      (70%), focal neurologic complaints (numbness, weakness, aphasia) (29%), seizure
      (24%), and head injury (12%). Ninety-four percent of patients had a focal
      neurologic finding in the ED. A likely contributing cause of thrombosis was
      identified in all but one patient. More than half of the patients had been
      evaluated in the ED in the previous 60 days. Two patients died, both as a result
      of their thrombosis and resulting cerebral infarctions and edema. Of the patients
      who survived, 80% had a good functional outcome. CONCLUSIONS: CVST is rare, but
      it can have significant associated morbidity and mortality. Whereas the clinical
      outcome and functional outcomes of treated patients can vary, prompt recognition
      of the disease is important.

PMID- 20031366
TI  - Mirtazapine intoxication in a child.

PMID- 20031367
TI  - Pilot study on documentation skills: is there adequate training in emergency
      medicine residency?
AB  - BACKGROUND: Thorough and accurate documentation in the medical record is
      important, and documentation skills should be an integral component of emergency
      medicine (EM) residency training. STUDY OBJECTIVE: We sought to study the
      documentation skills of EM residents as they relate to emergency department (ED)
      reimbursement. METHODS: This was a retrospective, cross-sectional study. We
      reviewed all charts of patients presenting to the adult ED during a 2-week
      period. We compared three groups: patients seen primarily by an EM resident,
      patients seen primarily by a physician assistant (PA), and patients seen
      primarily by an attending emergency physician. Outcome measures were the
      incidence of downcodes and dollars lost to downcodes in all groups. RESULTS:
      There were 212 patients in the resident group, 683 patients in the PA group, and
      437 patients in the attending group. There were 12 downcodes (5.7%, 95%
      confidence interval [CI] 2.96-9.70) in the resident group, 10 downcodes (1.5%,
      95% CI 0.70-2.68) in the PA group, and 17 downcodes (3.9%, 95% CI 2.28-6.14) in
      the attending group (p = 0.002). The mean dollar lost per patient seen in the
      resident group was $3.21 (95% CI 1.41-5.00); $0.91 (95% CI 0.33-1.49) in the PA
      group; and $2.23 (95% CI 1.17-3.28) in the attending group (p = 0.002).
      CONCLUSION: Charts documented primarily by EM residents were more likely to be
      downcoded than charts documented primarily by PAs or ED attendings. This downcode
      rate resulted in a greater loss of revenue in the resident group. We believe this
      represents an area for improvement in EM residency education.

PMID- 20031368
TI  - Spontaneous lumbar artery pseudoaneurysm bleeding: a case report.

PMID- 20031369
TI  - Heavy in utero ethanol exposure is associated with the use of other drugs of
      abuse in a high-risk population.
AB  - Many ethanol dependent women also use other drugs of abuse that may affect
      pregnancy outcome and long-term child neurodevelopment. This study investigated
      the association between drugs of abuse and concurrent use of ethanol in
      pregnancy. A study cohort of neonates with FAEE levels above 2 nmol per gram
      meconium, indicative of heavy in utero ethanol exposure, was identified (n=114).
      Meconium and hair analyses for the presence of other drugs of abuse were obtained
      for some of these neonates and the rates of drug exposure were compared with the
      rates in a cohort of neonates who were tested negative (FAEE below 2 nmol per
      gram meconium) for ethanol exposure (n=622). Odds ratios (ORs) for various drugs
      were calculated with ethanol exposure. A 15.5% positive rate for intrauterine
      ethanol exposure was detected. A high rate of in utero drug exposure was detected
      in neonates with and without in utero ethanol exposure, 60.5% versus 62.7%
      respectively. Neonates with heavy in utero ethanol exposure were almost twice as
      likely to be exposed to narcotic opiates (OR=1.90; 95% confidence interval [CI]:
      1.13-3.20) and 3.3 times as likely to be exposed to amphetamine (OR=3.30; 95% CI
      1.06-10.27) when compared to neonates with no ethanol exposure. Exposure to
      cannabinoids predicted less likely exposure to ethanol (OR=0.61; 95% CI: 0.38
      0.98) and no significant difference was noted in the exposure to cocaine
      (OR=1.24, 95% CI: 0.81-1.91). Neonates suspected of heavy in utero ethanol
      exposure should be tested for other drugs of abuse and vice versa. Early
      detection of drug exposures can facilitate early intervention to both the neonate
      and the mother, thus decreasing the risk of long-term neurodevelopmental outcomes
      for the child, including secondary disabilities associated with fetal alcohol
      spectrum disorder.

PMID- 20031370
TI  - A hybrid CPG-ZMP control system for stable walking of a simulated flexible spine
      humanoid robot.
AB  - Biped humanoid robots have gained much popularity in recent years. These robots
      are mainly controlled by two major control methods, the biologically-inspired
      approach based on Central Pattern Generator (CPG) and the engineering-oriented
      approach based on Zero Moment Point (ZMP). Given that flexibility in the body
      torso is required in some human activities, we believe that it is beneficial for
      the next generation of humanoid robots to have a flexible spine as humans do. In
      order to cope with the increased complexity in controlling this type of robot, a
      new kind of control system is necessary. Currently, there is no controller that
      allows a flexible spine humanoid robot to maintain stability in real-time while
      walking with dynamic spine motions. This paper presents a new hybrid CPG-ZMP
      control system for the walking of a realistically simulated flexible spine
      humanoid robot. Experimental results showed that using our control method, the
      robot is able to adapt its spine motions in real-time to allow stable walking.
      Our control system could be used for the control of the next generation humanoid
      robots.

PMID- 20031371
TI  - The implications of autoimmunity and pregnancy.
AB  - There are multiple epidemiological studies that document the potential adverse
      affects of autoimmunity on nearly every aspect of reproduction, even in the
      absence of clinically manifest autoimmune disease. Two decades ago, it was
      suggested that women with autoimmune diseases avoid pregnancy due to inordinate
      risks to the mother and the child. In contrast, newer epidemiological data
      demonstrated that advances in the treatment of autoimmune diseases and the
      management of pregnant women with these diseases have similarly improved the
      prognosis for mother and child. In particular, if pregnancy is planned during
      periods of inactive or stable disease, the result often is giving birth to
      healthy full-term babies without increased risks of pregnancy complications.
      Nonetheless, pregnancies in most autoimmune diseases are still classified as high
      risk because of the potential for major complications. These complications
      include disease exacerbations during gestation and increased perinatal mortality
      and morbidity in most autoimmune diseases, whereas fetal mortality is
      characteristic of the anti-phospholipid syndrome (APS). In this review, we will
      discuss these topics, including issues of hormones, along with potential long
      term effects of the microchimerism phenomenon. With respect to pregnancy and
      autoimmune diseases, epidemiological studies have attempted to address the
      following questions: 1) Is it safe for the mother to become pregnant or are there
      acute or chronic effects of pregnancy on the course of the disease? 2) Does the
      disease alter the course and/or the outcome of a pregnancy and thereby represent
      an inordinate risk for the fetus and infant? And do new therapeutic and
      management approaches improve the pregnancy outcomes in women with autoimmune
      diseases? 3) Does passage of maternal autoantibodies represent a risk to the
      child? 4) Do pregnancy, parity, or other factors influencing hormonal status
      explain the female predominance of many autoimmune diseases, and is the pregnancy
      effect related to microchimerism? Answering these questions has taken on
      additional importance in recent decades as women in western countries now
      frequently choose to delay pregnancies and have some or all of their pregnancies
      after disease onset. In this paper, we primarily focus on APS, systemic lupus
      erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), and type
      1 diabetes (T1D).

PMID- 20031372
TI  - Nucleic acid-associated autoantigens: pathogenic involvement and therapeutic
      potential.
AB  - Autoimmunity to ubiquitously expressed macromolecular nucleic acid-protein
      complexes such as the nucleosome or the spliceosome is a characteristic feature
      of systemic autoimmune diseases. Disease-specificity and/or association with
      clinical features of some of these autoimmune responses suggest pathogenic
      involvement which, however, has been proven in only a few cases so far. Although
      the mechanisms leading to autoimmunity against nucleic acid-containing complexes
      are still far from being fully understood, there is increasing experimental
      evidence that the nucleic acid component may act as a co-stimulator or adjuvans
      via activation of nucleic acid-binding receptor systems such as Toll-like
      receptors in antigen-presenting cells. Dysregulated apoptosis and inappropriate
      stimulation of nucleic acid-sensing receptors may lead to loss of tolerance
      against the protein components of such complexes, activation of autoreactive T
      cells and formation of autoantibodies. This has been demonstrated to occur in
      systemic lupus erythematosus and seems to represent a general mechanism that may
      be crucial for the development of systemic autoimmune diseases. This review
      provides a comprehensive overview of the most thoroughly-characterized nucleic
      acid-associated autoantigens, describing their structure and biological function,
      as well as the nature and pathogenic importance of the reactivities directed
      against them. Furthermore, recent advances in immunotherapy such as antigen
      specific approaches targeted at nucleic acid-binding antigens are discussed.

PMID- 20031373
TI  - Electrographic high-frequency activity and epilepsy.
AB  - High-frequency electrographic activity (HFA) has a frequency of 80-600Hz. It can
      be observed interictally in epileptic foci and also at the onset of epileptic
      seizures. There are several hypotheses about how HFA is generated, and it has
      been suggested that the underlying mechanisms may play an important role in
      epileptogenesis and ictogenesis. The high specificity of HFA for epileptic foci
      is now used during presurgical evaluation to help localize epileptic focus. In
      this article we review the current state of knowledge regarding this phenomenon
      and challenges for the future studies focusing on HFA.

PMID- 20031374
TI  - The clinical value of chloral hydrate in the routine electroencephalogram.
AB  - PURPOSE: To evaluate the diagnostic yield and clinical impact of chloral hydrate
      (CH) in the routine EEG. METHODS: The EEG results and records of all patients
      receiving CH during routine EEG (CH-EEG) at Mayo Clinic Rochester between 4/1/07
      and 9/30/07 (n=216 total; 148 adults) were reviewed for clinical indication,
      presence of epileptiform abnormalities and EEG duration. The results were
      compared to an equivalent number of consecutive EEGs performed without CH over
      the same time period (non-CH-EEGs). The clinical impact of the CH-EEG findings
      was evaluated by evaluating resulting clinical decisions made in the medical
      record. Chi-squared analysis was performed for discontinuous data, Student's t
      test for continuous data. RESULTS: The proportion of EEGs with sleep-specific
      epileptiform abnormalities (SSEAs) was not statistically different (7.8% CH-EEG
      vs. 10.5% non-CH-EEG, p=0.34). CH was ordered more often by non-epileptologists
      than epileptologists (57% vs. 35%, p=0.0004). The mean acquisition time was
      greater for CH-EEGs (66.9min vs. 55.1min; p<<0.001). CH-EEGs resulted in a change
      in clinical management in 5/216 (2.3%). DISCUSSION: Compared to non-CH-EEGs, CH
      EEGs were no more likely to show SSEAs, prolonged the acquisition time, and were
      associated with changes in clinical care in <3%. Routine use of CH in outpatient
      EEG is not strongly supported by these data.

PMID- 20031375
TI  - In vitro interference of beta-lactams with biofilm development by prevalent
      community respiratory tract isolates.
AB  - Interference of cefditoren (CDN) and amoxicillin/clavulanic acid (AMC) with
      biofilm production was studied using 11 Streptococcus pneumoniae isolates with
      minimum inhibitory concentrations (MICs) ranging from 0.015microg/mL to
      0.5microg/mL for CDN and from 0.06microg/mL to 2microg/mL for AMC (except for one
      isolate with an AMC MIC of 8microg/mL) and 5 Haemophilus influenzae isolates with
      MICs of 0.03-0.06microg/mL for CDN and 0.5-16microg/mL for AMC. Slime production
      was assessed in antibiotic-free medium and with 0.03microg/mL CDN or
      1/0.5microg/mL AMC by measuring the optical density at 450nm (OD(450)).
      Significantly lower mean OD(450) values were obtained for S. pneumoniae with
      antibiotics compared with controls (CDN, 0.088 vs. 0.118, P=0.003; and AMC, 0.095
      vs. 0.112, P=0.003), with significant correlation between both antibiotics
      (r=0.752; P=0.008). Percent reduction in OD(450) values was higher for CDN
      compared with AMC (24.02% vs. 15.92%; P=0.008). For H. influenzae, significantly
      lower mean OD(450) values were obtained with CDN compared with controls (0.083
      vs. 0.096; P=0.043) but not with AMC (0.086 vs. 0.095; P=0.08). Comparing percent
      reductions in S. pneumoniae versus H. influenzae for each antibiotic, no
      differences were found for AMC (15.92% vs. 9.40%; P=0.36), with a tendency for
      CDN (24.02% vs. 13.79%; P=0.069). Different beta-lactams may have different
      capabilities of interfering with S. pneumoniae biofilm development when tested
      under the same experimental conditions.

PMID- 20031376
TI  - Phenotypic characterisation of Clostridium difficile reveals lack of
      extracellular virulence factor production and significant differences in
      antibiogram profiles.

PMID- 20031377
TI  - The designer proline-rich antibacterial peptide A3-APO is effective against
      systemic Escherichia coli infections in different mouse models.
AB  - Antimicrobial peptides are considered to be viable alternatives to conventional
      antibiotics. However, they rarely show systemic efficacy in animal models when
      added at non-toxic doses. The dimer A3-APO was designed to attack both the
      bacterial membrane and the Enterobacteriaceae-specific domain of the heat shock
      protein DnaK in order to reduce toxicity whilst maintaining activity. The peptide
      exhibited a minimal inhibitory concentration (MIC) range of 2-128 mg/L against 28
      clinical Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar
      Typhimurium strains, with a median MIC of 30 mg/L. At this concentration, A3-APO
      was bactericidal to E. coli 5770, a fluoroquinolone-resistant extended-spectrum
      beta-lactamase-producing strain. The No Observed Adverse Effect Limit (NOAEL) at
      repeated intraperitoneal peptide administration was 20mg/kg. When administered at
      this dose three times starting immediately after E. coli Neumann infection, A3
      APO cured 100% of mice in a standard bacteraemia model used by the pharmaceutical
      industry. In a more stringent assay, when treatment started after E. coli 5770
      bacteraemia had already been established, three doses of 10mg/kg A3-APO prolonged
      early survival at a rate similar to that of imipenem and reduced the bacterial
      counts to base level. When the second assay was repeated in kidney clearance
      conditions resembling those in humans, 10mg/kg A3-APO was as efficacious as
      imipenem in the long-term. The increased in vivo efficacy compared with the in
      vitro bactericidal figures can potentially be explained by the generally
      observable immunostimulatory properties of antimicrobial peptides. Peptide A3-APO
      shows promising features as a member in our antibiotic arsenal against multidrug
      resistant bacterial pathogens.

PMID- 20031378
TI  - Antimicrobial and immunomodulatory activities of an ovine proline/arginine-rich
      cathelicidin.
AB  - In in vitro co-culture experiments, the ovine-derived cathelicidin OaBac5mini
      showed antimicrobial activity against Escherichia coli cells and modulated
      production of a cytokine by a mammalian inflammatory cell type (macrophage).
      Using atomic force microscopy, the morphology of peptide-treated E. coli bacteria
      showed no cell lysis, indicating an intracellular mode of action of the peptide
      leading to bacterial cell inhibition. At a concentration of 50microg/mL
      OaBac5mini, the peptide suppressed production of the inflammatory cytokine
      interleukin-12 by murine J774A cells that had been stimulated with Staphylococcus
      aureus strain Cowan; levels of other cytokines were unaffected. Thus, certain
      cationic peptides can enter and disrupt invading Gram-negative pathogens and may
      be able to modulate inflammatory responses induced by Gram-positive bacterial
      products.

PMID- 20031379
TI  - Inhibition of Listeria monocytogenes infection by neurological drugs.
AB  - To gain insights into the cellular processes required for intracellular bacterial
      pathogenesis, we previously developed a generalisable screening approach to
      identify small molecule compounds that alter Listeria monocytogenes infection. In
      this report, a small molecule library enriched for compounds affecting
      neurological functions was screened and 68 compounds that disrupted L.
      monocytogenes infection of macrophages were identified. Many of these compounds
      were known antimicrobial agents, however 26 compounds were novel inhibitors of
      intracellular infection. Two of the compounds chosen for further study, the
      antipsychotic drug thioridazine and the calcium channel blocker bepridil,
      exhibited dose-dependent inhibition of vacuolar escape and intracellular
      replication of L. monocytogenes during infection of murine macrophages. These
      results suggest that clinically approved neurological drugs may provide a novel
      source of anti-infective agents that are suitable for development as therapeutics
      against intracellular bacterial infections.

PMID- 20031380
TI  - Effects of one serving of mixed nuts on serum lipids, insulin resistance and
      inflammatory markers in patients with the metabolic syndrome.
AB  - BACKGROUND AND AIMS: Knowledge of the effect of nut consumption on metabolic
      syndrome (MetS) components is limited. We assessed the effects of nut intake on
      adiposity, serum lipids, insulin resistance, and inflammatory biomarkers in
      patients with MetS. METHODS AND RESULTS: In a randomized, parallel-group, 12-week
      feeding trial, 50 patients with MetS were given recommendations for a healthy
      diet with or without supplementation with 30 g/day of raw nuts (15 g walnuts, 7.5
      g almonds and 7.5 g hazelnuts) (Nut and Control diet groups, respectively).
      Adiposity measures, serum lipids, insulin, Homeostasis Model Assessment (HOMA),
      interleukin-6 (IL-6) and other inflammatory biomarkers, and 48-h fecal fat were
      determined basally and at study's completion. Moderate weight loss, decreased
      adiposity, and lower blood pressure occurred similarly after both diets. The
      Control, but not the Nut diet, was associated with significant (P<0.05) reduction
      of LDL-cholesterol, with mean changes of -0.36 versus -0.13 mmol/L, respectively
      (between-group differences, P=0.154). The Nut diet reduced fasting insulin by
      2.60 MUU/mL (95% CI, -4.62 to -0.59) and HOMA-insulin resistance by 0.72 (-1.28
      to -0.16) (P<0.05 versus Control diet; both). Among inflammatory markers, the Nut
      diet resulted in changes of median plasma IL-6 of -1.1 ng/L (-2.7 to -0.1;
      P=0.035 versus Control diet), but adjustment for weight loss attenuated the
      significance of the association. Stool fat decreased with the Control diet and
      slightly increased with the Nut diet (P<0.05 for between-group differences).
      CONCLUSION: Patients with MetS show decreased lipid responsiveness but improved
      insulin sensitivity after daily intake of 30 g of mixed nuts.

PMID- 20031381
TI  - Metabolic toxicity of the heart: insights from molecular imaging.
AB  - There is convincing evidence that alterations in myocardial substrate use play an
      important role in the normal and diseased heart. In this review, insights gained
      by using quantitative molecular imaging by positron emission tomography and
      magnetic resonance spectroscopy in the study of human myocardial metabolism will
      be discussed, and attention will be paid to the effects of nutrition, gender,
      aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure. The
      heart is an omnivore organ, relying on metabolic flexibility, which is
      compromised by the occurrence of defects in coronary flow reserve, insulin
      mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes,
      and ischemic cardiomyopathy appear as states of high uptake and oxidation of
      fatty acids, that compromise the ability to utilize glucose under stimulated
      conditions, and lead to misuse of energy and oxygen, disturbing mechanical
      efficiency. Idiopathic heart failure is a complex disease frequently coexisting
      with diabetes, insulin resistance and hypertension, in which the end stage of
      metabolic toxicity manifests as severe mitochondrial disturbance, inability to
      utilize fatty acids, and ATP depletion. The current literature provides evidence
      that the primary events in the metabolic cascade outlined may originate in extra
      cardiac organs, since fatty acid, glucose levels, and insulin action are mostly
      controlled by adipose tissue, skeletal muscle and liver, and that a broader
      vision of organ cross-talk may further our understanding of the primary and the
      adaptive events involved in metabolic heart toxicity.

PMID- 20031383
TI  - Mechanics of cytokinesis in eukaryotes.
AB  - Research on eukaryotic cytokinesis using advantageous model systems is rapidly
      advancing our understanding of most aspects of the process. Cytokinesis is very
      complicated with more than 100 proteins participating. Both fungi and animal
      cells use proteins to mark the cleavage site for the assembly of a contractile
      ring of actin filaments and myosin-II. Formins nucleate and elongate the actin
      filaments and myosin-II helps to organize the filaments into a contractile ring.
      Much is still to be learned about the organization of the contractile ring and
      the mechanisms that disassemble the ring as it constricts. Although fungi and
      animals share many proteins that contribute to cytokinesis, the extent to which
      they share mechanisms for the location, assembly, constriction, and disassembly
      of their contractile rings is still in question.

PMID- 20031384
TI  - From signaling pathways to microtubule dynamics: the key players.
AB  - Microtubules are highly dynamic structures whose regulation is crucial for cell
      division, cell polarity, cell migration, or neuronal differentiation. Because
      they contribute to most cellular functions, they must be regulated in response to
      extracellular and intracellular signals. The parameters of microtubule dynamics
      are numerous and complex and the connection between signaling pathways and
      regulation of microtubule dynamics remain obscure. Recent observations reveal key
      players that can both integrate the diversity of signaling cascades and directly
      influence microtubule dynamics. I review here how modifications of the tubulin
      dimer, tubulin modifying enzymes, and microtubule-associated proteins are
      directly involved in the regulation of microtubule behavior and functions.

PMID- 20031385
TI  - Decision support system for the optimal location of electrical and electronic
      waste treatment plants: a case study in greece.
AB  - Environmentally sound end-of-life management of Electrical and Electronic
      Equipment has been realised as a top priority issue internationally, both due to
      the waste stream's continuously increasing quantities, as well as its content in
      valuable and also hazardous materials. In an effort to manage Waste Electrical
      and Electronic Equipment (WEEE), adequate infrastructure in treatment and
      recycling facilities is considered a prerequisite. A critical number of such
      plants are mandatory to be installed in order: (i) to accommodate legislative
      needs, (ii) decrease transportation cost, and (iii) expand reverse logistics
      network and cover more areas. However, WEEE recycling infrastructures require
      high expenditures and therefore the decision maker need to be most precautious.
      In this context, special care should be given on the viability of infrastructure
      which is heavily dependent on facilities' location. To this end, a methodology
      aiming towards optimal location of Units of Treatment and Recycling is developed,
      taking into consideration economical together with social criteria, in an effort
      to interlace local acceptance and financial viability. For the decision support
      system's needs, ELECTRE III is adopted as a multicriteria analysis technique. The
      methodology's applicability is demonstrated with a real-world case study in
      Greece.

PMID- 20031386
TI  - Feasibility study of the separation of chlorinated films from plastic packaging
      wastes.
AB  - This study describes the possible separation of chlorinated plastic films (PVC
      and PVDC) from other heavy plastic packaging waste (PPW) by selective twist
      formation and gravity separation. Twists formation was mechanically induced in
      chlorinated plastic films, whereas twist formation did not occur in PS and PET
      films. After twist formation, all the films had the apparent density of less than
      1.0g/cm(3) and floated in water even though the true density was more than
      1.0g/cm(3). However, the apparent density of the PS and the PET films increased
      with agitation to more than 1.0g/cm(3), whereas that of chlorinated plastic films
      was kept less than 1.0g/cm(3). The main reason would be the air being held inside
      the chlorinated plastic films which was difficult to be removed by agitation.
      Simple gravity separation after twist formation was applied for artificial film
      with 10wt.% of the chlorinated films and real PPW films with 9wt.% of the
      chlorinated films. About 76wt.% of the artificial PPW films and 75wt.% of real
      PPW films after the removal of PP and PE were recovered as settling fraction with
      4.7wt.% and 3.0wt.% of chlorinated plastic films, respectively. These results
      indicate that simple gravity separation process after twist formation can be used
      to reduce the chlorinated plastic concentration from mixed heavy PPW films.

PMID- 20031387
TI  - Selective collection and detection of leukemia cells on a magnet-quartz crystal
      microbalance system using aptamer-conjugated magnetic beads.
AB  - A novel method for selective collection and detection of human acute leukemia
      cells has been proposed using aptamer-conjugated magnetic beads (apt-MBs) and a
      magnet-quartz crystal microbalance (QCM) system. The sgc8c aptamer-conjugated MBs
      specifically binding to CCRF-CEM cells were used for target cell extraction from
      complex matrixes, and the magnet-QCM system was successfully applied for
      quantitative cell detection, requiring no further labeling of cells. The
      accumulation of MBs-conjugated CCRF-CEM cells on a quartz crystal gold electrode
      surface under a magnetic field resulted in decreased resonant frequency. A linear
      relationship between the frequency shift and cell concentration over the range of
      1 x 10(4)-1.5 x 10(5)cells mL(-1) was obtained, with a detection limit of 8 x
      10(3)cells mL(-1). The applicability of the method for target cell detection from
      cell mixture was satisfactory.

PMID- 20031389
TI  - Association between CYP2E1 genetic polymorphisms and lung cancer risk: a meta
      analysis.
AB  - Genetic variations in metabolic genes are thought to modify the metabolic process
      of carcinogens and are suggested to be related to cancer risk. However,
      epidemiological results are not always consistent. In this meta-analysis, we
      assessed reported studies of associations between polymorphisms of CYP2E1
      RsaI/PstI and DraI, and the risk of lung cancer. We found decreased lung cancer
      risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotype
      [odds ratio (OR)=0.80, 95% confidence interval (CI): 0.72-0.89 and OR=0.82, 95%
      CI: 0.72-0.93, respectively], using 4436 cases and 6385 controls from 26 studies.
      We also observed a decreased lung cancer risk among subjects carrying c1/c2 and
      c1/c2+c2/c2 genotypes in the Asian population and on the basis of population
      control in stratified analysis. We found a protective effect of the CYP2E1 DraI
      CC and CD+CC polymorphisms for lung cancer (OR=0.58, 95% CI: 0.41-0.81 and
      OR=0.84, 95% CI: 0.73-0.96, respectively). The meta-analysis suggests that CYP2E1
      RsaI/PstI and DraI polymorphisms may affect the susceptibility of lung cancer,
      and a study with a larger sample size is needed to further evaluate gene
      environment interaction on CYP2E1 polymorphisms and lung cancer risk.

PMID- 20031388
TI  - High metastatic efficiency of human sarcoma cells in Rag2/gammac double knockout
      mice provides a powerful test system for antimetastatic targeted therapy.
AB  - Immunodeficient animal models are invaluable tools to investigate the metastatic
      propensity of human tumours. However residual immune responses, in particular
      natural killer (NK) cells, severely hamper the traffic and growth of human tumour
      cells. We studied whether a genetically modified mouse host lacking T, B and NK
      immunity allowed an improved expression of the metastatic phenotype of malignant
      human tumours. Metastatic spread of a panel of human sarcoma cell lines was
      studied in double knockout Rag2(-/-);gammac(-/-) mice in comparison with NK
      depleted nude mice. Rag2(-/-);gammac(-/-) mice receiving intravenous (i.v.) or
      subcutaneous (s.c.) human sarcoma cell lines developed extensive multiorgan
      metastases. Metastatic efficiency in Rag2(-/-);gammac(-/-) was superior than in
      nude mice in terms of both metastatic sites and metastasis number. Metastatic
      growth in Rag2(-/-);gammac(-/-) mice was faster than that in nude mice, thus
      allowing an earlier metastasis evaluation. Most human sarcomas metastasised in
      the liver of Rag2(-/-);gammac(-/-) mice, a kind of organ preference undetectable
      in nude mice and specific of sarcomas, as several carcinoma cell lines failed to
      colonise the liver of Rag2(-/-);gammac(-/-) mice, independently of their
      metastatic spread to other sites. In vitro analysis of the molecular mechanisms
      of liver metastasis of sarcomas implicated liver-produced growth and motility
      factors, in particular the insulin-like growth factor (IGF) axis. NVP-BEZ235, a
      specific inhibitor of downstream signal transduction targeting PI3K and mTOR,
      strongly inhibited liver metastasis of human sarcoma cells. In conclusion, the
      Rag2(-/-);gammac(-/-) mouse model allowed the expression of human metastatic
      phenotypes inapparent in conventional immunodeficient mice and the preclinical
      testing of appropriate targeted therapies.

PMID- 20031390
TI  - Evaluation of the safety of C-1311 (SYMADEX) administered in a phase 1 dose
      escalation trial as a weekly infusion for 3 consecutive weeks in patients with
      advanced solid tumours.
AB  - PURPOSE: C-1311 is a member of the novel imidazoacridinone family of anticancer
      agents. This phase 1 trial was designed to investigate the safety, tolerability
      and preliminary anti-tumour activity of C-1311. PATIENTS AND METHODS: This was a
      phase 1, inter-subject dose escalating and pharmacokinetic study of intravenous
      (IV) C-1311, administered weekly during 3consecutive weeks followed by 1week rest
      (constituting 1 cycle) in subjects with advanced solid tumours. RESULTS: Twenty
      two (22) patients were treated with C-1311, the highest dose given was
      640mg/m(2). All subjects experienced one or more treatment-related adverse events
      (AEs). The most frequently observed treatment-related AEs were neutropaenia and
      nausea (50% each), followed by vomiting (27%), anaemia (23%), asthenia (23%) and
      diarrhoea (18%). Most treatment-related AEs were of Common Terminology Criteria
      for Adverse Events (CTCAE) grades 1-2, except for the blood and lymphatic system
      disorders, which were primarily of grades 3-4. The recommended dose (RD) of C
      1311 administered as once weekly IV infusions for 3weeks every 4weeks is
      480mg/m(2), with the dose limiting toxicity (DLT) being grade 4 neutropaenia
      lasting more than 7days. Treatment at this dose offers a predictable safety
      profile and excellent tolerability. CONCLUSION: The safety profile and
      preliminary anti-tumour efficacy of C-1311, observed in this broad-phase dose
      finding study, warrants further evaluation of the compound.

PMID- 20031391
TI  - New data tells us more about cancer incidence in North Africa.
AB  - Over the last few years, Cancer Registries in North Africa (Morocco, Algeria,
      Tunisia, Libya and Egypt) increased in number from one to nine, and now covers
      13% of the total regional population. Their data can be considered of good or
      acceptable quality, according to available indicators. The pattern of risk shown
      by these Registries is quite unique. The total cancer burden in the North African
      countries is between one third and one half of what is observed in Europe. The
      overall incidence rate in men (world age standardised, per 100,000) ranges from
      86.3 in Setif, Algeria, to 156.1 in Garbiah, Egypt. The range is similar in
      women: from 80.3 in Setif to 164.0 in Algier, both in Algeria. The case mix and
      the level of rates are quite homogeneous in the countries considered. The most
      frequent cancers are the same as in Europe (Lung, Breast and Prostate). This
      pattern completely differs from that of Central and Southern African countries,
      where infection-related cancers are predominant. The well-known excess risk for
      nasopharyngeal carcinoma in this area is confirmed, with rates reaching the level
      of 5.4 in men and 1.9 in women, which is 10 times higher than that in Europe.

PMID- 20031382
TI  - Add-on montelukast in inadequately controlled asthma patients in a 6-month open
      label study: the MONtelukast In Chronic Asthma (MONICA) study.
AB  - Bronchial asthma often remains uncontrolled despite treatment with inhaled
      corticosteroids (ICS), long-acting beta(2)-agonists (LABA) or both, necessitating
      additional treatment. Patients >or=18 years (n=1681) with mild-to-moderate asthma
      received oral montelukast 10mg added to ICS or ICS+LABAs, and were followed for 6
      months in a prospective, open-label observational study. The primary endpoint was
      change in Asthma Control Test (ACT) score. Secondary endpoints included mini
      Asthma Quality-of-Life Questionnaire (mini-AQLQ) and FEV(1)/PEF. Mean ACT scores
      improved from 14.6+/-4.6 (baseline) to 19.4+/-4.4 (month 6; p<0.0001). Using ACT
      score categories, the percentage of patients with uncontrolled (57.5%) or poorly
      controlled (25.0%) asthma at baseline decreased at month 6 (17.6 and 21.7%,
      respectively); the percentage of patients with well controlled (13.9%) or
      completely controlled (1.2%) asthma at baseline increased at month 6 (47.5 and
      11.4%, respectively). The mini-AQLQ score (mean+/-SD) improved from 4.0+/-1.1 to
      5.3+/-1.1 (p<0.0001); FEV(1) increased from 2.46+/-0.89 to 2.60+/-0.92L
      (p<0.0001). Treatment with montelukast was generally well tolerated. In patients
      insufficiently controlled with ICS or ICS+LABAs, daily add-on montelukast
      improved both asthma control and asthma-related quality of life.
      Clinicaltrials.gov registry number NCT00802789.

PMID- 20031392
TI  - Effect of oral clodronate on bone mass, bone turnover and subsequent metastases
      in women with primary breast cancer.
AB  - Breast cancer treatments have been associated with accelerated bone loss and
      increased osteoporosis risk. In a subgroup analysis of a randomised, double
      blind, placebo-controlled study, we compared the changes in spine and total hip
      bone mineral density (BMD) and biochemical markers of bone turnover in women with
      primary breast cancer who had received standard therapy plus either oral
      clodronate 1600 mg/d (n=419) or placebo (n=432) for 2 years. After 2 years, spine
      BMD was 1.92% higher in patients who received clodronate instead of placebo
      (P<0.0001) and total hip BMD was 1.29% higher (P=0.002 versus placebo). Patients
      who received clodronate had a median 26% reduction in levels of serum N-terminal
      pro-peptide of type I procollagen (PINP)--a marker of bone turnover--after 2
      years of therapy. This compares with a median 5% increase in patients who
      received placebo (P<0.0001). Effects on BMD, but not biochemical markers,
      persisted for up to 3 years post-treatment. Early changes in PINP were associated
      with changes in BMD and the likelihood of developing bone metastases. This study
      shows the use of oral clodronate during primary breast cancer treatment is
      associated with reduced bone turnover and protection against bone metastases.

PMID- 20031393
TI  - Liquefaction of bio-mass in hot-compressed water for the production of phenolic
      compounds.
AB  - Direct liquefaction of lignocellulosic wastes (sawdust and cornstalks) and two
      model bio-mass compounds (pure lignin and pure cellulose as references) has been
      conducted in hot-compressed water at temperatures from 250 to 350 degrees C in
      the presence of 2MPa H(2), for the production of phenolic compounds that may be
      suitable for the production of green phenol-formaldehyde resins. The liquefaction
      operations at 250 degrees C for 60 min produced the desirable product of
      phenolic/neutral oil at a yield of about 53, 32, 32 and 17 wt.% for lignin,
      sawdust, cornstalk and cellulose, respectively. The yield of phenolic/neutral oil
      for each feedstock was found to decrease with increasing temperature. As
      evidenced by GC-MS measurements, significant quantities of phenolic compounds
      such as 2-methoxy-phenol, 4-ethyl-2-methoxy-phenol, and 2,6-dimethoxy-phenol,
      were present in the resulting phenolic/neutral oils from the two lignocellulosic
      wastes and pure lignin. The relative concentration of phenolic compounds in the
      lignin-derived oil was as high as about 80%. As expected, the liquid products
      from cellulose contained essentially carboxylic acids and neutral compounds.
      Addition of Ba(OH)(2) and Rb(2)CO(3) catalysts were found to significantly
      increase both phenolic/neutral oil and gas yields for all feedstocks except for
      lignin.

PMID- 20031394
TI  - Production of bioethanol from wheat straw: An overview on pretreatment,
      hydrolysis and fermentation.
AB  - Wheat straw is an abundant agricultural residue with low commercial value. An
      attractive alternative is utilization of wheat straw for bioethanol production.
      However, production costs based on the current technology are still too high,
      preventing commercialization of the process. In recent years, progress has been
      made in developing more effective pretreatment and hydrolysis processes leading
      to higher yield of sugars. The focus of this paper is to review the most recent
      advances in pretreatment, hydrolysis and fermentation of wheat straw. Based on
      the type of pretreatment method applied, a sugar yield of 74-99.6% of maximum
      theoretical was achieved after enzymatic hydrolysis of wheat straw. Various
      bacteria, yeasts and fungi have been investigated with the ethanol yield ranging
      from 65% to 99% of theoretical value. So far, the best results with respect to
      ethanol yield, final ethanol concentration and productivity were obtained with
      the native non-adapted Saccharomyses cerevisiae. Some recombinant bacteria and
      yeasts have shown promising results and are being considered for commercial scale
      up. Wheat straw biorefinery could be the near-term solution for clean, efficient
      and economically-feasible production of bioethanol as well as high value-added
      products.

PMID- 20031395
TI  - On-farm production of inoculum of indigenous arbuscular mycorrhizal fungi and
      assessment of diluents of compost for inoculum production.
AB  - On-farm production of arbuscular mycorrhizal [AM] fungus inoculum can be employed
      to make the benefits of the symbiosis more available to vegetable farmers.
      Experiments were conducted to modify an existing method for the production of
      inoculum in temperate climates to make it more readily adoptable by farmers.
      Perlite, vermiculite, and peat based potting media were tested as diluents of
      yard clippings compost for the media in which the inoculum was produced using
      bahiagrass (Paspalum notatum Flugge) as host plant. All produced satisfactory
      concentrations of AM fungus propagules, though vermiculite proved to be better
      than potting media (89 vs. 25 propagules cm(-3), respectively). Two methods were
      tested for the growth of AM fungi indigenous to the farm: (1) adding field soil
      into the vermiculite and compost mixture and (2) pre-colonizing the bahiagrass
      seedlings in media inoculated with field soil prior to transplant into that
      mixture. Adding 100 cm(3) of field soil to the compost and vermiculite produced
      465 compared to 137 propagules cm(-3) for the pre-colonization method. The
      greater flexibility these modifications give will make it easier for farmers to
      produce inoculum of AM fungi on-the-farm.

PMID- 20031396
TI  - Very stable silica-gel-bound laccase biocatalysts for the selective oxidation in
      continuous systems.
AB  - Cerrena unicolor laccase was immobilized by adsorption and covalent bonds
      formation on silica-gel carriers, functionalized with different organosilanes and
      surface densities. The effects of protein concentration, pH value of the coupling
      mixture and the enzyme purity on immobilization efficiency of the best carrier,
      moderately modified (0.75 mmol/g carrier) with 3-aminopropyltriethoxysilane were
      investigated. Activity of the best biocatalysts, expressed in ABTS oxidation, was
      4028 U/mL of the carrier or 3530 U/mg of bound protein. Properties of immobilized
      laccase were determined to find excellent thermal stability improvement; t(1/2)
      for freely suspended enzyme was 2-3 min at 80 degrees C, whereas after
      immobilization over 100 min. Kinetic experiments in both batch and packed-bed
      reactors gave only four times lower k(cat)/K(m) value than for the native enzyme.
      A packed-bed reactor with silica-gel-bound laccase beads appeared to be very
      efficient in ABTS oxidation and its exceptional potentials were shown in the
      continuous decolorization of indigo carmine for 18 days without loss in activity.
      This system offers perfect ability to degrade recalcitrant dyes, but we can also
      envisage its use, with ABTS acting as a mediator, in regeneration of nicotinamide
      cofactors.

PMID- 20031397
TI  - Model of a polyethylene microporous hollow-fiber membrane biofilm reactor
      inoculated with Pseudomonas putida strain To1 1A for gaseous toluene removal.
AB  - A diffusion and reaction model is presented for a gas phase membrane biofilm
      reactor (MBfR) that overcomes many of limitations of conventional biofilters. The
      model considers transfer of toluene from the gas phase through the membrane and
      into a toluene degrading biofilm. Data from bench-scale tests of toluene removal
      in an MBfR were used to validate the model. Overall mass transfer coefficients
      were 0.64 x 10(-3), 1.1 x 10(-3), 1.86 x 10(-3) (ms(-1)) at liquid flow rates
      (shell-side) of 4, 7, and 9 L min(-1), respectively. Modeled mass transfer
      coefficients were in good agreement with experimental values. The bench-scale
      MBfR was capable of removing more than 98% of the influent toluene (an overall
      removal rate of 17 g m(-3)min(-1)) at an inlet concentration of 100 ppm(v) and a
      gas flow rate of 1.0 L min(-1) (gas residence time of 1.3s in the membrane
      lumen). Model predictions were well in agreement with experimental values.

PMID- 20031398
TI  - Degradation of naproxen and carbamazepine in spiked sludge by slurry and solid
      phase Trametes versicolor systems.
AB  - Growth and activity of the white-rot fungus Trametes versicolor on sewage sludge
      were assessed in bioslurry and solid-phase systems. Bioslurry cultures with
      different loads of sludge (10%, 25% and 38%, w/v) were performed. A lag phase of
      at least 2 d appeared in the 25 and 38%-cultures, however, the total fungal
      biomass was higher for the latter and lower for the 10%-culture after 30 d, as
      revealed by ergosterol determination. Detectable laccase activity levels were
      found in the 10 and 25%-cultures (up to 1308 and 2588 AUL(-1), respectively)
      while it was negligible in the 38%-culture. Important levels of ergosterol and
      laccase were obtained over a 60 d period in sludge solid-phase cultures amended
      with different concentrations of wheat straw pellets as lignocellulosic bulking
      material. Degradation experiments in 25%-bioslurry cultures spiked with naproxene
      (NAP, analgesic) and carbamazepine (CBZ, antiepileptic) showed depletion of
      around 47% and 57% within 24h, respectively. Complete depletion of NAP and around
      48% for CBZ were achieved within 72 h in sludge solid cultures with 38% bulking
      material. CBZ degradation is especially remarkable due to its high persistence in
      wastewater treatment plants. Results showed that T. versicolor may be an
      interesting bioremediation agent for elimination of emerging pollutants in sewage
      sludge.

PMID- 20031399
TI  - Production of polyhydroxyhexadecanoic acid by using waste biomass of
      Sphingobacterium sp. ATM generated after degradation of textile dye Direct Red
      5B.
AB  - The degradation of textile effluent using microorganisms has been studied
      extensively, but disposal of generated biomass after dye degradation is a serious
      problem. The isolated Sphingobacterium sp. ATM was found to decolorize dye Direct
      Red 5B (DR5B) and simultaneously it produced polyhydroxyhexadecanoic acid (PHD).
      The organism decolorized DR5B at 500mgl(-1) concentration within 24h of dye
      addition and gave optimum production of PHD. The medium contains carbon source as
      a molasses which was found to be more significant within all carbon sources used.
      The Nuclear Magnetic Resonance spectroscopy (NMR), Fourier Transform Infrared
      spectroscopy (FTIR) and Gas Chromatography-Mass Spectroscopy (GC-MS)
      characterization of polyhydroxyalkanoates obtained revealed the compound as a
      polyhydroxyhexadecanoic acid. The activity of PHA synthase was found more at 24h
      after dye addition. The enzymes responsible for dye degradation include veratrol
      oxidase, laccase, DCIP (2,6-dichlorophenol-indophenol) reductase, riboflavin
      reductase and azo reductase was found to be induced during decolorization
      process. The FTIR analysis of samples before and after decolorization of dye
      confirmed the biotransformation of DR5B. The GC-MS analysis of product obtained
      led to the identification of two metabolites after biotransformation of dye as p
      amino benzenesulfonic acid and naphthalene-1-ol.

PMID- 20031400
TI  - Purification and characterization of a thermostable intra-cellular beta
      glucosidase with transglycosylation properties from filamentous fungus
      Termitomyces clypeatus.
AB  - An intra-cellular beta-glucosidase was purified to homogeneity by gel filtration,
      ion exchange chromatography and HPGPLC from mycelial extract of Termitomyces
      clypeatus in the presence of the glycosylation inhibitor 2-deoxy-d-glucose. CD
      spectroscopy demonstrated that the purified enzyme exhibited alpha-helical
      conformation. MALDI-TOF identified the enzyme's molecular weight as 6688Daltons,
      but SDS-PAGE and immunoblotting indicated that the enzyme formed aggregates. The
      enzyme also showed unique properties of co-aggregation with sucrase in the
      fungus. The enzyme showed around 80% stability up to 60 degrees C and residual
      activity was 80-100% between pH ranges 5-8. The enzyme had higher specific
      activity against p-nitrophenyl-d-glucopyranoside than cellobiose and HPLC showed
      that the enzyme possesses transglycosylation activity and synthesizes cello
      oligosaccharides by addition of glucose. The enzyme will be useful in synthetic
      biology to produce complex bioactive glycosides and to avoid chemical hazards.
      This is the first report of a beta-glucosidase enzyme with such a low monomeric
      unit size.

PMID- 20031401
TI  - Identification and SAR of novel pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives as
      inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1).
AB  - Herein we describe the discovery of a novel series of pyrrolo[1,2-a]pyrazin-1(2H)
      one PARP inhibitors. Optimization led to compounds that display excellent PARP-1
      enzyme potency and inhibit the proliferation of BRCA deficient cells in the low
      double-digit nanomolar range showing excellent selectivity over BRCA proficient
      cancer cells.

PMID- 20031402
TI  - Molecular design of small organic molecules based on structural information for a
      conformationally constrained peptide that binds to G-CSF receptor.
AB  - Based on structural information for a peptide (P8-2KAQ) that binds to granulocyte
      colony stimulating factor receptor (G-CSFR), small ligands with a biaryl scaffold
      were designed and their binding affinities were evaluated.

PMID- 20031403
TI  - Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in
      silico derived hits. Part 1.
AB  - Structure-activity relationships of three related series of 4-phenylthiazol-5
      ylacetic acids, derived from two hits emanating from a focused library obtained
      by in silico screening, have been explored as CRTH2 (chemoattractant receptor
      homologous molecule expressed on Th2 cells) antagonists. Several compounds with
      double digit nanomolar binding affinity and full antagonistic efficacy for human
      CRTH2 receptor were obtained in all subclasses. The most potent compound was [2
      (4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding
      affinity of 3.7nM and functional antagonistic effect of 66 nM in a BRET and 12 nM
      in a cAMP assay with no functional activity for the other PGD2 DP receptor (27
      microM in cAMP).

PMID- 20031404
TI  - Synthesis and application of a photoaffinity analog of dehydroepiandrosterone
      (DHEA).
AB  - We have synthesized an analog of dehydroepiandrosterone (DHEA, 1) containing both
      a benzophenone (BP) and a biotin (Bt) group (DHEA-BP-Bt, 8). Compound 8 was
      prepared by functionalization on C-17 of 1. Biocytin was reacted with 4
      benzoylbenzoic acid and the product was condensed with 1 containing a diamine
      hexane linker. We detected specific protein bands of approximately 55, 80, and
      150 kDa by SDS-PAGE analysis of vascular endothelial cell plasma membranes which
      had been photoirradiated in the presence of 8.

PMID- 20031405
TI  - Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV
      inhibitor for the treatment of type 2 diabetes.
AB  - Design, synthesis, and SAR are described for a class of DPP-IV inhibitors based
      on aminobenzo[a]quinolizines with non-aromatic substituents in the S1 specificity
      pocket. One representative thereof, carmegliptin (8p), was chosen for clinical
      development. Its X-ray structure in complex with the enzyme and early efficacy
      data in animal models of type 2 diabetes are also presented.

PMID- 20031406
TI  - Synthesis and evaluation of two series of 4'-aza-carbocyclic nucleosides as
      adenosine A2A receptor agonists.
AB  - The synthesis of two series of 4'-aza-carbocyclic nucleosides are described in
      which the 4'-substituent is either a reversed amide, relative to the carboxamide
      of NECA, or an N-bonded heterocycle. Using established purine substitution
      patterns, potent and selective examples of agonists of the human adenosine A(2A)
      receptor have been identified from both series. The propionamides 14-18 and the 4
      hydroxymethylpyrazole 32 were determined to be the most potent and selective
      examples from the 4'-reversed amide and 4'-N-bonded heterocyclic series,
      respectively.

PMID- 20031407
TI  - Syntheses and antibacterial activity studies of new oxazolidinones from nitroso
      Diels-Alder chemistry.
AB  - A series of novel oxazolidinone antibiotics having [2.2.1] and [2.2.2] bicyclic
      oxazine moieties at the C-5 side chain of the A-ring was synthesized by nitroso
      Diels-Alder reactions, from three linezolid analogs containing morpholine,
      piperazine and thiomorpholine, respectively, as the C-ring components. Subsequent
      N-O bond cleavage generated oxazolidinones with 4-amino cyclo-2-en-1-ol
      substituents. The in vitro antibacterial activities of these oxazolidinone
      analogs were evaluated.

PMID- 20031409
TI  - Photoactive ligands probing the sweet taste receptor. Design and synthesis of
      highly potent diazirinyl D-phenylalanine derivatives.
AB  - Some D-amino acids such as d-tryptophan and D-phenylalanine are well known as
      naturally-occurring sweeteners. Photoreactive D-phenylalanine derivatives
      containing trifluoromethyldiazirinyl moiety at 3- or 4-position of phenylalanine,
      were designed as sweeteners for functional analysis with photoaffinity labeling.
      The trifluoromethyldiazirinyl D-phenylalanine derivatives were prepared
      effectively with chemo-enzymatic methods using L-amino acid oxidase and were
      found to have potent activity toward the human sweet taste receptor.

PMID- 20031408
TI  - Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl
      peptidase IV inhibitors.
AB  - Synthesis and SAR are described for a structurally distinct class of DPP-IV
      inhibitors based on aminobenzo[a]quinolizines bearing (hetero-)aromatic
      substituents in the S1 specificity pocket. The m-(fluoromethyl)-phenyl derivative
      (S,S,S)-2g possesses the best fit in the S1 pocket. However, (S,S,S)-2i, bearing
      a more hydrophilic 5-methyl-pyridin-2-yl residue as substituent for the S1
      pocket, displays excellent in vivo activity and superior drug-like properties.

PMID- 20031410
TI  - Design, synthesis, and pharmacological evaluation of phenoxy pyridyl derivatives
      as dual norepinephrine reuptake inhibitors and 5-HT1A partial agonists.
AB  - Preclinical studies suggest that compounds with dual norepinephrine reuptake
      inhibitor (NRI) and 5-HT(1A) partial agonist properties may provide an important
      new therapeutic approach to ADHD, depression, and anxiety. Reported herein is the
      discovery of a novel chemical series with a favorable NRI and 5-HT(1A) partial
      agonist pharmacological profile as well as excellent selectivity for the
      norepinephrine transporter over the dopamine transporter.

PMID- 20031411
TI  - Piperidine-based heterocyclic oxalyl amides as potent p38 alpha MAP kinase
      inhibitors.
AB  - The design and synthesis of a new class of p38alpha MAP kinase inhibitors based
      on 4-fluorobenzylpiperidine heterocyclic oxalyl amides are described. Many of
      these compounds showed low-nanomolar activities in p38alpha enzymatic and cell
      based cytokine TNFalpha production inhibition assays. The optimal linkers between
      the piperidine and the oxalyl amide were found to be [6,5] fused ring
      heterocycles. Substituted indoles and azaindoles were favored structural motifs
      in the cellular assay.

PMID- 20031412
TI  - Synthesis and SAR of novel imidazoles as potent and selective cannabinoid CB2
      receptor antagonists with high binding efficiencies.
AB  - The synthesis and structure-activity relationship studies of imidazoles are
      described. The target compounds 6-20 represent a novel chemotype of potent and
      CB(2)/CB(1) selective cannabinoid CB(2) receptor antagonists/inverse agonists
      with very high binding efficiencies in combination with favourable logP and
      calculated polar surface area values. Compound 12 exhibited the highest CB(2)
      receptor affinity (K(i)=1.03 nM) in this series, as well as the highest
      CB(2)/CB(1) subtype selectivity (>9708-fold).

PMID- 20031413
TI  - Adult age differences in familiarization to treadmill walking within virtual
      environments.
AB  - We assessed age-related differences in adults in familiarization to treadmill
      walking within virtual environments (VE), and examined whether treadmill walking
      after familiarization resembles overground walking. Seventeen younger and 17
      older adults walked at preferred speed on an overground walkway and afterwards
      walked at the same speed for 20 min on a treadmill coupled to a VE. A motion
      capture system was used to measure spatio-temporal gait parameters. On the
      treadmill, both younger and older adults initially displayed decreased step
      length and increased step width, cadence, and time in double support relative to
      overground walking. Except for time in double support, step characteristics
      approached overground walking-behavior with a negatively accelerated trend. After
      15 min of treadmill walking, changes became minor corresponding to less than 1%
      deviations to individuals' overground walking. At the end of familiarization,
      average differences in step length, cadence, and double support relative to
      overground walking were reduced to less than 5 percent in both age groups. For
      step width, younger adults approximated overground walking after 20 min more
      closely than older adults, probably reflecting larger initial differences between
      treadmill and overground walking among older adults. We conclude (a) that 20 min
      of familiarization to treadmill walking in a VE are sufficient to reach stable
      walking patterns resembling those observed in overground walking, but that some
      differences between the two settings remain, especially in older adults; (b) that
      sufficient familiarization to the treadmill is needed to ascertain the validity
      and generalizability of comparisons between younger and older adults.

PMID- 20031414
TI  - Ocular dominance and balance performance in healthy adults.
AB  - PURPOSE: To evaluate the effect of ocular dominance on balance performance in
      healthy adult subjects. METHODS: Ocular dominance was determined in 24 healthy
      subjects using the hole-in-the-paper test. Balance function was evaluated by
      computerized dynamic platform posturography (CDPP). Sway index (SI), antero
      posterior sway (APS) and lateral sway (LS) were served as outcome parameters.
      RESULTS: The outcome parameters did not differ significantly between dominant and
      non-dominant eye fixation both in static and angular balance tests (SI-5.47+/
      0.42, 6.23+/-0.52, p=0.146 and 18.4+/-1.07, 19.11+/-1.15, p=0.142, respectively;
      APS--2.26+/-4.68, -5.1+/-4.6, p=0.082 and -1.94+/-3.33, -3.64+/-2.6, p=0.48,
      respectively; LS--1.21+/-1.46, -1.12+/-1.66 p=0.94 and -1.98+/-1.16, -1.55+/
      1.39, p=0.69, respectively). CONCLUSIONS: Ocular dominance does not seem to
      affect postural function in the monovision and far viewing condition.

PMID- 20031416
TI  - New heteroaryl nitrones with spin trap properties: Identification of a 4
      furoxanyl derivative with excellent properties to be used in biological systems.
AB  - A new series of heteroaryl nitrones, 1-7, bearing furoxanyl and thiadiazolyl
      moieties, were evaluated for their free radical-trapping properties. The
      physicochemical characterization by electron paramagnetic resonance (EPR)
      demonstrated its capability to trap and stabilize oxygen-, carbon-, sulfur-, and
      nitrogen-centered free radicals. The 4-furoxanyl nitrone 3 (FxBN), alpha(Z)-(3
      methylfuroxan-4-yl)-N-tert-butylnitrone, showed appropriate solubility in aqueous
      solution and taking into account that this physicochemical property is very
      important for biological applications, we studied it deeply in terms of its
      trapping and kinetic behaviors. For this, kinetic studies of the hydroxyl adduct
      decay gave rate constants k(ST) of 1.22x10(10)dm(3)mol(-1)s(-1) and half-live up
      to 7200s at physiological pH, without any artifactual signals. The ability of
      FxBN to directly traps and stabilizes superoxide free radical, with a half-life
      of 1620s at physiological pH, was also demonstrated. Besides, FxBN-hydroxyl and 
      superoxide adducts exhibited distinct and characteristic EPR spectral patterns.
      Finally, we confirmed the ability of FxBN to act as spin trap in a specific
      biological system, that is, in the free radical production of experimental anti
      trypanosomatid drugs using Trypanosoma cruzi microsomes as biological system.
      Moreover, previous observations of low FxBN toxicity transform it in a good
      candidate for in vivo spin trapping.

PMID- 20031417
TI  - Labeled 3-aryl-4-indolylmaleimide derivatives and their potential as angiogenic
      PET biomarkers.
AB  - In a continued effort to find a suitable PET tracer for visualization of
      angiogenic processes, we explored the 3,4-diarylmaleimide family, known to have
      high affinity and selectivity towards the VEGFR-TKs. One previously reported
      agent and three new halogen-containing 3,4-diarylmaleimide derivatives were
      synthesized. The four maleimide derivatives were evaluated for their affinity and
      selectivity towards the VEGFRs and exhibited promising results. An automated
      carbon-11 radiolabeling route with a total synthesis time of 50min successfully
      labeled the lead compound, resulting in 1.55+/-0.15GBq of tracer with a
      radiochemical yield of 20+/-2%, 96% radiochemical purity and a SA of 111+/
      22GBq/micromol (EOB, n=5). The tracer possessed high stability in in vitro blood
      stability tests and specific VEGFR-TK binding profiles in intact cell binding
      experiments. Tracer lipophilicity was evaluated in an n-octanol/phosphate buffer
      system giving a LogD(7.4) of 1.99+/-0.04. For the in vivo experiments, two animal
      models were used. The first was a U87 glioma tumor model, frequently reported in
      the literature and the second, a newly developed 293/KDR tumor model. Both models
      were validated for VEGFR-2 expression and used in in vivo biodistribution
      studies. These studies revealed low accumulation and rapid washout of the tracer
      from tumor tissue. High accumulation of activity in the liver prompted us to
      examine the tracer's in vitro stability to liver microsomes, revealing low
      resistance to P450 metabolism. In spite of encouraging in vitro results, the
      labeled lead tracer failed to accumulate in VEGFR-2 overexpressing tumors. It is
      possible that poor resistance to P450 metabolism reduces tracer's circulation
      leading to low tumor accumulation.

PMID- 20031415
TI  - Potential role for mucosally active vaccines against pneumococcal pneumonia.
AB  - Pneumococcal pneumonia is a life-threatening disease with high mortality and
      morbidity among children under 5 years of age, the elderly and immunocompromised
      individuals worldwide. Protection against pneumococcal pneumonia relies on
      successful regulation of colonisation in the nasopharynx and a brisk alveolar
      macrophage-mediated immune response in the lung. Therefore, enhancing pulmonary
      mucosal immunity (which includes a combination of innate, humoral and cell
      mediated immunity) through mucosal vaccination might be the key to prevention of
      pneumococcal infection. Current challenges include a lack of information in
      humans on mucosal immunity against pneumococci and a lack of suitable adjuvants
      for new vaccines. Data from mouse models, however, suggest that mucosally active
      vaccines will enhance mucosal and systemic immunity for protection against
      pneumococcal infection.

PMID- 20031418
TI  - Identification of novel allosteric nonpeptidergic inhibitors of the human
      cytomegalovirus-encoded chemokine receptor US28.
AB  - Human cytomegalovirus (HCMV) is a widespread human pathogen, possessing onco
      modulatory properties. Constitutive signaling of the HCMV-encoded chemokine
      receptor US28 and its ability to bind a broad spectrum of chemokines might
      facilitate HCMV-associated tumor progression. Novel nonpeptidergic chemotypes
      were identified as neutral antagonists or inverse agonists on US28, that
      allosterically inhibit chemokine binding to US28.

PMID- 20031419
TI  - Synthesis of structurally simplified analogues of aplidinone A, a pro-apoptotic
      marine thiazinoquinone.
AB  - The synthesis of analogues of aplidinone A (7), a prenylated quinone isolated
      from the Mediterranean ascidian Aplidium conicum, has been performed. This work
      not only allowed confirming the structural assignment of aplidinone A, previously
      made with the support of GIAO shielding calculations, but, above all, made a
      series of structurally related quinone derivatives (compounds 8-13 and the
      natural metabolite) available for a screening in vitro for cytotoxic and pro
      apoptotic activity and for SAR studies. The study evidenced one of the synthetic
      analogues (11) as a potent cytotoxic and pro-apoptotic agent against several
      tumor cell lines which also inhibits the TNFalpha-induced NF-kappaB activation in
      a human leukemia T cell line. This exemplifies the potential of a natural product
      to qualify as lead structure for medicinal chemistry campaigns, affording
      simplified analogues with better bioactivity and easier to synthesize.

PMID- 20031420
TI  - Click synthesis of estradiol-cyclodextrin conjugates as cell compartment
      selective estrogens.
AB  - Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing
      aqueous solubility. CDs themselves are anticipated to have low membrane
      permeability because of relatively high hydrophilicity and molecular weight. CD
      derivatization with 17-beta estradiol (E(2)) was explored extensively using a
      number of different click chemistries and the cell membrane permeability of
      synthetic CD-E(2) conjugate was explored by cell reporter assays and confocal
      fluorescence microscopy. In simile with reported dendrimer-E(2) conjugates, CD
      E(2) was found to be a stable, extranuclear receptor selective estrogen that
      penetrated into the cytoplasm.

PMID- 20031421
TI  - Synthesis, DNA binding, fluorescence measurements and antiparasitic activity of
      DAPI related diamidines.
AB  - A novel series of extended DAPI analogues were prepared by insertion of either a
      carbon-carbon triple bond (16a-d) or a phenyl group (21a,b and 24) at position-2.
      The new amidines were evaluated in vitro against both Trypanosoma brucei
      rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.). Five compounds (16a,
      16b, 16d, 21a, 21b) exhibited IC(50) values against T. b. r. of 9nM or less which
      is two to nine folds more effective than DAPI. The same five compounds exhibited
      IC(50) values against P. f. of 5.9nM or less which is comparable to that of DAPI.
      The fluorescence properties of these new molecules were recorded, however; they
      do not offer any advantage over those of DAPI.

PMID- 20031422
TI  - Design and synthesis of selective inhibitors of placental alkaline phosphatase.
AB  - Placental Alkaline Phosphatase (PLAP) is a tissue-restricted isozyme of the
      Alkaline Phosphatase (AP) superfamily. PLAP is an oncodevelopmental enzyme
      expressed during pregnancy and in a variety of human cancers, but its biological
      function remains unknown. We report here a series of catechol compounds with
      great affinity for the PLAP isozyme and significant selectivity over other
      members of the AP superfamily. These selective PLAP inhibitors will provide small
      molecule probes for the study of the pathophysiological role of PLAP.

PMID- 20031423
TI  - Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design,
      synthesis and biological evaluation as potential anticancer agents.
AB  - A series of novel quinazolinone linked pyrrolobenzodiazepine (PBD) conjugates
      were synthesized. These compounds 4a-f and 5a-f were prepared in good yields by
      linking C-8 of DC-81 with quinazolinone moiety through different alkane spacers.
      These conjugates were tested for anticancer activity against 11 human cancer cell
      lines and found to be very potent anticancer agents with GI(50) values in the
      range of <0.1-26.2microM. Among all the PBD conjugates, one of the conjugate 5c
      was tested against a panel of 60 human cancer cells. This compound showed
      activity for individual cancer cell lines with GI(50) values of <0.1microM. The
      thermal denaturation studies exhibited effective DNA binding ability compared to
      DC-81 and these results are further supported by molecular modeling studies. The
      detailed biological aspects of these conjugates on A375 cell line were studied.
      It was observed that compounds 4b and 5c induced the release of cytochrome c,
      activation of caspase-3, cleavage of PARP and subsequent cell death. Further,
      these compounds when treated with A375 cells showed the characteristic features
      of apoptosis like enhancement in the levels of p53, p21 and p27 inhibition of
      cyclin dependent kinase-2 (CDK2) and suppression of NF-kappaB. Moreover, these
      two compounds 4b and 5c control the cell proliferation by regulating anti
      apoptotic genes like (B-cell lymphoma 2) Bcl-2. Therefore, the data generated
      suggests that these PBD conjugates activate p53 and inhibit NF-kappaB and thereby
      these compounds could be promising anticancer agents with better therapeutic
      potential for the suppression of tumours.

PMID- 20031424
TI  - The separation of X-ray diffraction patterns for threat detection.
AB  - We introduce a novel method for identifying materials using a series of X-ray
      diffractograms collected in transmission. A multiple perspective approach is used
      to identify the diffractograms produced by materials located at different
      positions along the primary X-ray beam. This technique promises to enhance
      materials identification performance in cluttered environments such as those
      prevalent in aviation security screening.

PMID- 20031425
TI  - An automated ionization chamber for secondary radioactivity standards.
AB  - I report on the operation and characterization of a new ionization chamber
      system, "AUTOIC", featuring a commercial digital electrometer and a commercial
      robotic sample changer. The relative accuracy of the electrometer was improved
      significantly beyond the manufacturer's specifications through an in-house
      calibration of the various ranges, applied via software. The measurement
      precision and repeatability of the system have been determined by measuring
      multiple samples of the same radionuclide over the span of two or three years.
      The linearity of the system was examined by following the decay of (99m)Tc,
      (99)Mo and (133)Xe sources for up to 19 half-lives and determining half-life
      values. All of these values agree with the accepted literature values, within
      their combined uncertainties.

PMID- 20031426
TI  - Neutron fluence depth profiles in water phantom on epithermal beam of LVR-15
      research reactor.
AB  - Horizontal channel with epithermal neutron beam at the LVR-15 research reactor is
      used mainly for boron neutron capture therapy. Neutron fluence depth profiles in
      a water phantom characterise beam properties. The neutron fluence (approximated
      by reaction rates) depth profiles were measured with six different types of
      activation detectors. The profiles were determined for thermal, epithermal and
      fast neutrons.

PMID- 20031427
TI  - Activity standardization of 3H with the new TDCR system at PTB.
AB  - A triple-to-double coincidence ratio (TDCR) liquid scintillation counting system
      (Pochwalski et al., 1988; Grau Malonda and Coursey, 1988) was set up at the
      Physikalisch-Technische Bundesanstalt (PTB) to be used as an additional technique
      for primary activity standardization. The optical chamber of the system was
      designed in our laboratory, expending great effort to achieve maximum light
      transmission to the photomultiplier tubes (PMT) and, consequently, a maximum
      counting efficiency and low uncertainties. A programme to compute the counting
      efficiencies and to analyse the measurement data was developed and tested. The
      software can also be used to allow for PMT asymmetries. The system and recently
      developed analysis procedures were used for the activity standardization of a
      tritiated water solution within the scope of an international comparison under
      the auspices of the Bureau International des Poids et Mesures (BIPM).

PMID- 20031428
TI  - Methodological analysis of gamma tomography system for large random packed
      columns.
AB  - Gamma ray tomography experiments have been carried out to detect spatial patterns
      in the porosity in a 0.27 m diameter column packed with steel Rashig rings of
      different sizes: 12.6, 37.9, and 76 mm. using a first generation CT system (Chen
      et al., 1998). A fast Fourier transform tomographic reconstruction algorithm has
      been used to calculate the spatial variation over the column cross section. Cross
      sectional gas porosity and solid holdup distribution were determinate. The values
      of cross-sectional average gas porosity were epsilon=0.849, 0.938 and 0.966 for
      the 12.6, 37.9, and 76 mm rings, respectively. Radial holdup variation within the
      packed bed has been determined. The variation of the circumferentially averaged
      gas holdup in the radial direction indicates that the porosity in the column wall
      region is a somewhat higher than that in the bulk region, due to the effect of
      the column wall.

PMID- 20031429
TI  - Simulation of Cherenkov photons emitted in photomultiplier windows induced by
      Compton diffusion using the Monte Carlo code GEANT4.
AB  - The implementation of the TDCR method (Triple to Double Coincidence Ratio) is
      based on a liquid scintillation system which comprises three photomultipliers; at
      LNHB, this counter can also be used in the beta-channel of a 4pi(LS)beta-gamma
      coincidence counting equipment. It is generally considered that the gamma
      sensitivity of the liquid scintillation detector comes from the interaction of
      the gamma-photons in the scintillation cocktail but when introducing solid gamma
      ray emitting sources instead of the scintillation vial, light emitted by the
      surrounding of the counter is observed. The explanation proposed in this article
      is that this effect comes from the emission of Cherenkov photons induced by
      Compton diffusion in the photomultiplier windows. In order to support this
      assertion, the creation and the propagation of Cherenkov photons inside the TDCR
      counter is simulated using the Monte Carlo code GEANT4. Stochastic calculations
      of double coincidences confirm the hypothesis of Cherenkov light produced in the
      photomultiplier windows.

PMID- 20031430
TI  - Fe-55 activity measurements at the NMISA revisited.
AB  - Twenty years ago South Africa's Radioactivity Standards Laboratory (now operated
      by the NMISA) was the first to measure the activity of (55)Fe by combining the
      triple-to-double coincidence ratio (TDCR) liquid scintillation method with
      theoretical efficiency formulae. The extracted activity was however found to be
      consistently low by about 6%. Due to improvements in both the counting system and
      analysis technique, it was decided to re-examine the method as applied at the
      NMISA. The latest results are presented and discussed, particularly with regard
      to a quantitative study into which vial type is better suited to obtaining
      accurate (55)Fe activity measurements.

PMID- 20031431
TI  - Radioactivity evaluation of Ebro river water and sludge treated in a potable
      water treatment plant located in the South of Catalonia (Spain).
AB  - A potable water treatment plant with an average production rate of 4.3m(3)/s,
      providing several cities in the south of Catalonia (Spain) with drinking water,
      has been studied for a period of six years (2002-2007) regarding its capacity to
      remove several natural and anthropogenic radionuclides. First, gross alpha, gross
      beta and tritium activities were determined in ingoing and outgoing water
      samples. The values for all these parameters were below the Spanish normative
      limits established for waters for human consumption. For the sludge samples
      generated in the plant, we quantified some gamma emitting radioisotopes: natural
      ((40)K, (214)Pb, etc.) and artificial ((60)Co, (110m)Ag, etc.) which may be
      related to the geological or/and industrial activities (such as a nuclear power
      plant) located upstream of the PWTP on the Ebro River. Finally, when the sludge
      samples were compared with those from other water treatment plants, the influence
      of the industrial activities on the radioisotopes found in the analysed samples
      was confirmed since the activity levels for some of the isotopes quantified were
      10 times higher.

PMID- 20031432
TI  - New type of cells with multiple chromosome rearrangements.
AB  - A comparative analysis of the distribution and the frequency of multiaberrant
      cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy)
      irradiated people was carried out. The highest MAC frequency was observed in
      people exposed to alpha-radiation (Pu, Rn) and in cosmonauts. This fact allows
      MAC to be considered as an indicator of a high-energy local exposure. A new type
      of cells with multiple chromosome rearrangements was discovered in the course of
      analysis of stable aberrations by the fluorescence in situ hybridization (FISH)
      method. The biological consequences of MAC formation and possibility of revealing
      the whole diversity of cells with multiple aberrations by means of modern
      molecular-cytogenetic methods are discussed.

PMID- 20031433
TI  - Standardization of 241Am by digital coincidence counting, liquid scintillation
      counting and defined solid angle counting.
AB  - The nuclide (241)Am decays by alpha emission to (237)Np. Most of the decays
      (84.6%) populate the excited level of (237)Np with energy of 59.54 keV. Digital
      coincidence counting was applied to standardize a solution of (241)Am by alpha
      gamma coincidence counting with efficiency extrapolation. Electronic
      discrimination was implemented with a pressurized proportional counter and the
      results were compared with two other independent techniques: Liquid scintillation
      counting using the logical sum of double coincidences in a TDCR array and defined
      solid angle counting taking into account activity inhomogeneity in the active
      deposit. The results show consistency between the three methods within a limit of
      a 0.3%. An ampoule of this solution will be sent to the International Reference
      System (SIR) during 2009. Uncertainties were analysed and compared in detail for
      the three applied methods.

PMID- 20031434
TI  - Redox regulation of root apical meristem organization: connecting root
      development to its environment.
AB  - Post-embryonic root growth relies on the proliferative activity of the root
      apical meristem (RAM), consisting, in part, of cells with juvenile
      characteristics (stem cells). It is generally, but erroneously held that the RAM
      indefinitely produces new cells throughout the lifespan of a plant, resulting in
      indeterminate root growth. On the contrary, convincing data, mainly from the lab
      of Thomas L. Rost, show in all species analyzed so far, including Arabidopsis,
      that RAM organization changes over time in parallel with both a cessation of the
      production of new cells, and a consequent reduction in root growth, even under
      optimal conditions. In addition, RAM organization evolved to become highly
      plastic and dynamic in response to environmental triggers (e.g. water and
      nutrient availability, pollutants). Under unfavourable conditions, the RAM is
      rapidly reorganized, and, as a result of the cessation of new cell production at
      the root tip, root growth is altered, and lateral root production is enhanced,
      thus providing the plant additional strategies to overcome the stress. It is now
      becoming increasingly clear that this environment-responsive developmental
      plasticity is linked to reactive oxygen/nitrogen species, antioxidants, and
      related enzymes, which form part of a complex signalling module specifically
      operating in the regulation of RAM functioning, in strict relationship with
      hormonal control of root development exerted by auxin, gibberellins and
      cytokinins. In turn, such redox/hormone crosstalk regulates gene expression.

PMID- 20031435
TI  - Post-translational processing of beta-d-xylanases and changes in extractability
      of arabinoxylans during wheat germination.
AB  - Endo-1,4-beta-d-xylanase (EC 3.2.1.8, beta-d-xylanase) activity, and arabinoxylan
      (AX) level and extractability were monitored for the first time simultaneously in
      wheat kernels (Triticum aestivum cv. Glasgow) up to 24 days post-imbibition
      (DPI), both in the absence and presence of added gibberellic acid (GA). Roughly
      three different stages (early, intermediate and late) can be discriminated.
      Addition of GA resulted in a faster increase of water extractable arabinoxylan
      (WEAX) level in the early stage (up to 3-4 DPI). This increase was not
      accompanied by the discernible presence of homologues of the barley X-I beta-d
      xylanase as established by immunodetection. This suggests that other, yet
      unidentified beta-d-xylanases operate in this early time window. The intermediate
      stage (up to 13 DPI) was characterized by the presence of unprocessed 67 kDa X-I
      like beta-d-xylanase, which was much more abundant in the presence of GA. The
      occurrence of higher levels of the unprocessed enzyme was related with higher
      beta-d-xylanase activities and a further increase in WEAX level, pointing to in
      vivo activity of the unprocessed 67 kDa beta-d-xylanase. During the late stage
      (up to 24 DPI) gradual processing of the 67 kDa beta-d-xylanase occurred and was
      associated with a drastic increase in beta-d-xylanase activity. Up to 120-fold
      higher activity was recorded at 24 DPI, with approx. 85% thereof originating from
      the kernel remnants. The WEAX level decreased during the late stage, suggesting
      that the beta-d-xylanase is processed into more active forms to achieve extensive
      AX breakdown.

PMID- 20031436
TI  - Acute dissection of an ascending aorta vascular conduit.

PMID- 20031437
TI  - Strain rate imaging would predict sub-clinical acute rejection in heart
      transplant recipients.
AB  - OBJECTIVE: Non-invasive diagnosis of rejection is a major objective in the
      management of heart transplant recipients. The ability of strain rate (SR)
      imaging on echocardiograms to detect rejection in heart transplant recipients was
      investigated. METHODS: A total of 396 endomyocardial biopsies, right-heart
      catheterisation and echocardiograms were performed in 35 heart transplant
      recipients. Mean values of systolic strain (epsilon(sys)), peak systolic SR
      (SR(sys)), and peak early diastolic SR (SR(dia)) obtained from eight left
      ventricular segments were calculated. RESULTS: According to the conventional
      International Society for Heart and Lung Transplantation criteria, 351 biopsies
      showed a rejection grade (acute rejection, AR) of 0 or 1a (group AR(-)) whereas
      45 biopsies showed a grade of 1b or higher (group AR(+)). The epsilon(sys),
      SR(sys) and SR(dia) were significantly different between group AR(+) and group
      AR(-) (-20.7+/-8.0 vs -32.6+/-6.3%, p<0.0001, 2.5+/-1.8 vs 3.6+/-1.1/s, p<0.0001,
      and -1.9+/-1.6 vs -3.5+/-1.3/s, p<0.001, respectively). Multivariate analysis
      identified epsilon(sys) (p<0.0001) as a strong predictor for group AR(+), and
      epsilon(sys) cut-off value of -27.4% was associated with a predictive accuracy of
      82.3%. The combination of epsilon(sys) and SR(dia) discriminated group AR(+) from
      group AR(-) with a predictive accuracy of 84.8%. The pulmonary artery wedge
      pressure was higher in group AR(+) than that in group AR(-) (7.4+/-3.0 vs 9.4+/
      4.4 mm Hg, p<0.05). CONCLUSION: SR imaging is of potential clinical value for
      monitoring acute rejection in heart transplant recipients.

PMID- 20031438
TI  - Editorial comment: mind the step!

PMID- 20031439
TI  - Pulsatility index variations using two different transit-time flowmeters in
      coronary artery bypass surgery.
AB  - OBJECTIVE: Transit-time flow measurement is widely accepted as an intra-operative
      assessment in coronary artery bypass grafting (CABG). However, the two most
      commonly applied flowmeters, manufactured by MediStim ASA and Transonic Inc.,
      have different default filter settings of 20 and 10 Hz, respectively. This may
      cause different flow measurements, which will influence the reported results. The
      aim was to compare pulsatility index (PI) values recorded by the MediStim and
      Transonic flowmeters in two different clinical settings: (1) analysis of the flow
      patterns recorded simultaneously by both flowmeters in the same CABGs; and (2)
      evaluation of flow patterns under different levels of filter settings in the same
      grafts. METHODS: Graft flow and PI were measured using the two different
      flowmeters simultaneously in 19 bypass grafts. Finally, eight grafts were
      assessed under different digital filter settings at 5, 10, 20, 30, 50 and 100 Hz.
      RESULTS: The Transonic flowmeter provided substantially lower PI as compared with
      the MediStim flowmeter. By increasing the filter setting in the flowmeter, PI
      increased considerably. CONCLUSIONS: The Transonic flowmeter displayed a lower PI
      than the MediStim, due to a lower filter setting. In the Transonic,flow signals
      are filtered at a lower level, rendering a 'smoother' pattern of flow curves.
      Because different filter settings determine different PIs, caution must be taken
      when flow values and flowmeters are compared. The type of flowmeter should be
      indicated whenever graft flow measurements and derived indexes are provided
      [corrected].

PMID- 20031440
TI  - Postoperative acute superior mesenteric venous thrombosis after cardiac surgery
      in a patient with anti-phospholipid syndrome.

PMID- 20031441
TI  - Unusual presentation of catamenial pneumothorax.

PMID- 20031442
TI  - Apico-aortic bypass and concomitant replacement of a descending aorta containing
      severe atherosclerotic plaques.

PMID- 20031444
TI  - Increased plasma levels of osteopontin are associated with activation of the
      renin-aldosterone system and with myocardial and coronary microvascular damage in
      dilated cardiomyopathy.
AB  - In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow
      (MBF) has been associated with coronary microvascular dysfunction. The aim of
      this study was to test the hypothesis that osteopontin (OPN) plasma levels could
      be associated with the activation of the renin-aldosterone system (RAS) in these
      patients and be involved in mediating myocardial and coronary damage. In 66
      patients with idiopathic left ventricular dysfunction of variable severity the
      plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS
      activation, myocardial dysfunction and with clinical indexes of left ventricle
      (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared
      to controls, patients showed a significant increase of inflammatory markers (OPN:
      508+/-30.8ng/ml vs. 426.9+/-16.4, p<0.05 and interleukin (IL)-6: 1.71+/-0.29pg/ml
      vs. 0.38+/-0.03pg/ml, p<0.001) and of indexes of cardiac damage. OPN levels were
      significantly correlated with the extent of microvascular dysfunction (MBF at
      rest: p=0.01; during dipyridamole: p=0.0003) and with plasma renin activity (PRA)
      (r=0.26, p=0.04). Both in patients with milder or more severe LV dysfunction
      lower MBF values were associated with higher OPN levels and PRA. These results
      suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy.

PMID- 20031445
TI  - Mass analysis with islands of stability with linear quadrupoles incorporating
      higher order multipole fields.
AB  - Mass analysis with islands of stability has been investigated with three linear
      quadrupole mass filters: two with 4% added hexapole fields constructed with equal
      diameter (quadrupole 4A) and unequal diameter (quadrupole 4B) rods, and a
      conventional round-rod quadrupole that has apparently been slightly damaged.
      Islands are formed by applying auxiliary quadrupole excitation. With the Mathieu
      parameter, a < 0, mass analysis with both quadrupoles with hexapole fields
      operated normally, i.e., without islands, gives only low resolution. A factor of
      10 or more increase in resolution is possible with the use of stability islands.
      With a > 0, when quadrupole 4A is operated normally, peak shapes similar to that
      of a conventional quadrupole can be obtained at resolutions higher than 850. At
      lower resolutions, peaks are split. When quadrupole 4B is operated without
      islands, resolution up to 2000 is possible, but there are low mass tails and
      structure is formed on the peaks. With mass analysis with an island of stability,
      both quadrupoles 4A and 4B show peaks free of structure and without tails. Ion
      transmission is also improved with some operating conditions. With the
      conventional round-rod quadrupole, mass analysis with islands of stability
      increases the limiting resolution from 2500 to 4360. At a resolution of 2500, the
      transmission is increased by about two orders of magnitude. These results show
      that the use of islands of stability improves mass analysis with quadrupoles with
      distorted fields, and may, in the future, allow use of quadrupoles constructed
      with at least some lower mechanical tolerances.

PMID- 20031443
TI  - Pre-clinical whole-body fluorescence imaging: Review of instruments, methods and
      applications.
AB  - Fluorescence sampling of cellular function is widely used in all aspects of
      biology, allowing the visualization of cellular and sub-cellular biological
      processes with spatial resolutions in the range from nanometers up to
      centimeters. Imaging of fluorescence in vivo has become the most commonly used
      radiological tool in all pre-clinical work. In the last decade, full-body pre
      clinical imaging systems have emerged with a wide range of utilities and niche
      application areas. The range of fluorescent probes that can be excited in the
      visible to near-infrared part of the electromagnetic spectrum continues to
      expand, with the most value for in vivo use being beyond the 630 nm wavelength,
      because the absorption of light sharply decreases. Whole-body in vivo
      fluorescence imaging has not yet reached a state of maturity that allows its
      routine use in the scope of large-scale pre-clinical studies. This is in part due
      to an incomplete understanding of what the actual fundamental capabilities and
      limitations of this imaging modality are. However, progress is continuously being
      made in research laboratories pushing the limits of the approach to consistently
      improve its performance in terms of spatial resolution, sensitivity and
      quantification. This paper reviews this imaging technology with a particular
      emphasis on its potential uses and limitations, the required instrumentation, and
      the possible imaging geometries and applications. A detailed account of the main
      commercially available systems is provided as well as some perspective relating
      to the future of the technology development. Although the vast majority of
      applications of in vivo small animal imaging are based on epi-illumination planar
      imaging, the future success of the method relies heavily on the design of novel
      imaging systems based on state-of-the-art optical technology used in conjunction
      with high spatial resolution structural modalities such as MRI, CT or ultrasound.

PMID- 20031446
TI  - Influence of bovine serum albumin on the secondary structure of interferon alpha
      2b as determined by far UV circular dichroism spectropolarimetry.
AB  - Many therapeutic biologics are formulated with excipients, including the protein
      excipient human serum albumin (HSA), to increase stability and prevent protein
      aggregation and adsorption onto glass vials. One biologic formulated with albumin
      is interferon alpha-2b (IFN alpha-2b). As is the case with other therapeutic
      biologics, the increased structural complexity of IFN alpha-2b compared to a
      small molecule drug requires that both the correct chemical structure (amino acid
      sequence) and also the correct secondary and tertiary structures (3 dimensional
      fold) be verified to assure safety and efficacy. Although numerous techniques are
      available to assess a biologic's primary, secondary and tertiary structures,
      difficulties arise when assessing higher order structure in the presence of
      protein excipients. In these studies far UV circular dichroism spectropolarimetry
      (far UV-CD) was used to determine the secondary structure of IFN alpha-2b in the
      presence of a protein excipient (bovine serum albumin, BSA). We demonstrated that
      the secondary structure of IFN alpha-2b remains mostly unchanged at a variety of
      BSA to IFN alpha-2b protein ratios. A significant difference in alpha helix and
      beta sheet content was noted when the BSA to IFN alpha-2b ratio was 5:1 (w/w),
      suggesting a potential conformational change in IFN alpha-2b secondary structure
      when BSA is in molar excess.

PMID- 20031447
TI  - Swelling following percutaneous transluminal angioplasty for radiocephalic
      fistula mimicking hyperperfusion syndrome.

PMID- 20031448
TI  - Prospective study of a 'popping' sound during percutaneous radiofrequency
      ablation for hepatocellular carcinoma.
AB  - PURPOSE: To prospectively evaluate the occurrence of a 'popping' sound during
      radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) and its
      association with early tumor progression and patient survival. MATERIALS AND
      METHODS: Seventy-six patients with 100 tumors underwent RF ablation by using an
      internally cooled electrode. A popping sound was defined as an audible sound or
      tactile vibration detected by the operator during RF ablation. Follow-up ranged
      from 6 to 38 months (mean, 19 months) and included 3-6 month ultrasonography,
      serum alpha-fetoprotein measurements, and computed tomography or magnetic
      resonance imaging. Early local and distant intrahepatic tumor progression within
      12 months and survival were analyzed. RESULTS: A popping sound occurred during 58
      of the 100 (58%) tumor ablations. Primary technique effectiveness was achieved in
      97 of the 100 (97%) tumors. Major complications occurred in 2 of the 76 patients
      (2.6%). The cumulative rate of early local tumor progression was 20.8%. At
      multivariate analysis, early local tumor progression was associated with tumor
      size larger than 3 cm (odds ratio [OR] = 4.08, P = .012) and inversely associated
      with a popping sound (OR = 0.267, P = .026). The cumulative rate of early distant
      intrahepatic tumor progression was 21.4%, and the cumulative survival of the
      whole cohort at 6, 12, 18, and 24 months was 98.7%, 96%, 92.7%, and 83.6%,
      respectively. A popping sound was not significantly associated with either early
      distant intrahepatic tumor progression (P = .341) or patient survival (P = .975).
      CONCLUSIONS: A popping sound during RF ablation is not associated with an
      increased risk of early tumor progression or poorer patient survival.

PMID- 20031449
TI  - Successful recanalization of bile duct occlusion with a radiofrequency puncture
      wire technique.
AB  - A radiofrequency (RF) wire puncture technique was used in the recanalization of
      biliary anastomotic occlusions in five patients. The technical success of
      recanalization, which was defined as successful puncture and crossing of the
      obstruction followed by balloon cholangioplasty and internal-external biliary
      drainage without evidence of complications, was 100%. The average follow-up was
      13 months (range, 11-16 months). For biliary occlusion recanalization, the RF
      wire may allow the use of percutaneous therapy in the treatment of a subset of
      individuals who would otherwise have to undergo open surgical intervention.

PMID- 20031450
TI  - Epilepsy surgery program in Tunisia: an example of a Tunisian French
      collaboration.
AB  - OBJECTIVE: To describe the first Tunisian epilepsy surgery program establishment
      and to emphasize on its originality that is an exchange and surgery decision
      taken by two Mediterranean neurophysiological teams, via the Internet. METHODS:
      Patients with mesial temporal lobe epilepsy (MTLE) and refractory to
      antiepileptic drugs were included. A noninvasive protocol evaluation including a
      detailed history, neurological evaluation, brain imaging, scalp video-EEG
      monitoring and neuropsychological evaluation were performed. The different
      findings were discussed between the Neurophysiological Department of Charles
      Nicolle Hospital of Tunis and Rouen through the EUMEDCONNECT Internet network
      project. If cases of concordance of clinical, neuropsychological, neuroimaging
      data and video-EEG recordings, surgery was indicated. RESULTS: 15 patients (7
      women and 8 men) with mean age of 30 years were included. 10 patients had right
      hippocampal sclerosis (HS) and 5 had left HS. MRI findings were concordant with
      the ictal EEG in 12 patients. One patient had bitemporal ictal EEG abnormalities
      and right HS on MRI. One patient had contralateral ictal clinical and EEG
      patterns to the side of HS. One patient had temporal 'plus' epilepsy. Surgery was
      performed in 10 cases. After surgery, all patients are seizure free, with no
      operative mortality or major surgery complications. CONCLUSION: Our model of twin
      affiliations between advanced epilepsy surgery programs in a developed country
      and starting programs in a developing country, using Internet technology, can be
      a model for collaboration in other countries.

PMID- 20031451
TI  - Vohwinkel Syndrome secondary to missense mutation D66H in GJB2 gene (connexin 26)
      can include epileptic manifestations.
AB  - Vohwinkel Syndrome (VS) is a type of diffuse hereditary palmoplantar keratodermas
      (DHPPK) accompanied by skeletal dimorphisms and sensorineural deafness. The most
      frequently reported genetic substrate in VS is a point mutation of GJB2 gene,
      responsible for encoding connexin 26, a gap-junction protein with a crucial role
      in neuronal migration in rats. We report the case of a 21-year-old male who is a
      second-generation member of a family with VS and developed cryptogenic focal
      epilepsy. Genetic study showed a nucleotide change (c.196G>C) in exon 1 of GJB2
      gene, producing a missense mutation, D66H. It is plausible that a functional
      alteration of connexin 26, such as that resulting of the mutation of our case,
      can produce an alteration in cortical development with epileptogenic potential.
      The present case and experimental evidence that connexin 26 is related to animal
      epileptogenesis suggest that the phenotypic spectrum of VS could be expanded to
      include epileptic manifestations.

PMID- 20031452
TI  - Advanced carotid plaque imaging.
AB  - Treatment of carotid artery stenosis by endarterectomy or stenting can
      significantly reduce stroke risk. In clinical practice, indication for surgery or
      stenting is primarily based on the degree of stenosis, but there is growing
      awareness that pathophysiological features within a vulnerable plaque play a key
      role in predicting stroke risk. Important molecular processes associated with
      plaque vulnerability are inflammation, lipid accumulation, proteolysis,
      apoptosis, angiogenesis and thrombosis. The rapidly emerging field of molecular
      and functional imaging strategies allows identification of pathophysiological
      processes in carotid artery stenosis. We aimed to review the literature regarding
      the current most promising advanced imaging techniques in carotid artery disease.
      Various advanced imaging methods are available, such as high-resolution magnetic
      resonance imaging (HR-MRI), single photon emission computed tomography (SPECT),
      positron emission tomography (PET) and near-infrared fluorescence (NIRF).
      Radionuclide and fluorescent tracers that identify inflammation, apoptosis and
      proteolysis, such as FDG, MMP probes and Annexin A5, are promising. A combination
      of activity of molecular processes and detailed anatomic information can be
      obtained, providing a powerful tool in the identification of the vulnerable
      plaque. With these developments, we are entering a new era of imaging techniques
      in the selection of patients for carotid surgery.

PMID- 20031453
TI  - Effect of titanium implant surface nanoroughness and calcium phosphate low
      impregnation on bone cell activity in vitro.
AB  - BACKGROUND AND OBJECTIVE: In the field of bone implant surfaces, the effects of
      nanoscale modifications have received significant attention. In the present
      study, bone cell activity on 2 implant surfaces with similar microtopography but
      distinct chemistry and nanotopography (sandblasted/acid-etched surface as control
      group, and calcium phosphate (CaP) low impregnated surface (Ossean) as test
      group, both from Intra-Lock, Boca Raton, FL) were evaluated. STUDY DESIGN: The 2
      surfaces were characterized by X-ray photoelectronic spectroscopy (XPS) and
      scanning electron microscopy (SEM) up to x200,000 magnification. The micrometer
      level roughness profiles were evaluated by means of computer software. Cell
      adhesion, proliferation, and alkaline phosphatase activity were assessed with
      human SaOS-2 osteoblasts and bone mesenchymal stem cells in nonosteogenic culture
      conditions. RESULTS: The XPS and SEM results showed that the Ossean surface
      presented low levels of CaP impregnation within the titanium oxide layer and
      texturization at the nanometer scale (nanoroughness) compared with the control
      surface. Moreover Ossean surface induced significantly higher cell
      differentiation levels than the control (P < .01). CONCLUSION: This study showed
      that both homogeneous nanoroughness and CaP low impregnation differently affected
      in vitro bone cell behavior compared with the control moderately rough surface
      with less texturing in the nanometer scale. However, the relative importance of
      nanotopography and surface chemistry in cell reactions is yet to be determined.

PMID- 20031454
TI  - Detection of vertical root fracture using cone-beam computerized tomography: an
      in vitro assessment.
AB  - OBJECTIVES: This study aimed to compare 2 cone-beam CT units [NewTom 3G (small
      FOV), Iluma (ultra/low resolution)] and an intraoral CCD sensor in the detection
      of vertical root fracture (VRF). STUDY DESIGN: The VRFs were created in 30 teeth,
      and 30 intact teeth served as control samples. All images were evaluated twice by
      4 observers. Kappa coefficients were calculated to assess intra- and
      interobserver agreement, and t tests were used to compare Az values (alpha =
      0.05). RESULTS: Both intra- and interobserver agreement values were higher for
      the ultra-resolution Iluma and NewTom 3G images compared with the low-resolution
      Iluma and intraoral CCD images. Az values for the ultra-resolution Iluma and
      NewTom 3G images were also higher than for the Iluma low-resolution and intraoral
      CCD images. No significant differences (P > .05) in diagnostic accuracy were
      found between the Iluma ultra-resolution and NewTom 3G images, with the exception
      of the second reading of observer 2 (P = .036), and no significant differences (P
      > .05) were found between the intraoral digital and low-resolution Iluma images.
      CONCLUSION: Both ultra-resolution Iluma and NewTom 3G images performed better
      than low-resolution Iluma and intraoral CCD images in the detection of VRF.

PMID- 20031456
TI  - Misleading presentation of an orbital lymphangioma.
AB  - We describe a 2-year-old patient with an orbital lymphangioma who presented with
      massive proptosis. We highlight the importance of magnetic resonance imaging in
      evaluating such patients, because physical examination can be misleading. We also
      demonstrate the difficulties of managing recurrent hemorrhages when only subtotal
      excision is possible, as is frequently the case.

PMID- 20031455
TI  - Effect of Tisseel on bone healing with particulate dentin and plaster of Paris
      mixture.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of Tisseel on
      the early healing of bone defects in the skulls of rats. STUDY DESIGN: Forty
      eight rats were randomly assigned to 4 groups, and each group was further divided
      into 3 subgroups which were examined at 4 and 8 weeks after the defects were
      filled. The 4 different groups were animals containing: no graft (group 1);
      particulate dentin and plaster of Paris mixture graft (group 2); Tisseel and
      particulate dentin and plaster of Paris mixture graft (group 3); and Tisseel
      graft (group 4). After killing the animals at 4 and 8 weeks after surgery, all
      implant blocks were prepared for histologic sections and histomorphometric
      analysis. RESULTS: The overall new bone formation was significantly different
      between the 4-week samples and the 8-week samples. Significant differences
      between groups 1 and 2, groups 1 and 3, groups 1 and 4, groups 2 and 4, and
      groups 3 and 4 were observed at 4 weeks after surgery. At 8 weeks after surgery,
      significant differences between groups 1 and 2, groups 1 and 3, groups 1 and 4,
      and groups 2 and 4 were observed. As expected, effective bone formation was
      observed when the defects were filled with either particulate dentin, Tisseel, or
      particulate dentin-Tisseel combination. It was also observed from this study that
      particulate dentin is especially effective, followed by the particulate dentin
      Tisseel combination and Tisseel. CONCLUSION: It was concluded that the use of
      Tisseel may be an alternative therapy for regenerating bone in defects when used
      in combination with particulate dentin.

PMID- 20031457
TI  - Isolation of cervid herpesvirus 1 from the genital tract of a farmed red deer in
      Northern France.
AB  - In autumn 2008, several captive red deer in the North of France were found to be
      serologically positive for a ruminant alphaherpesvirus. A viral isolate obtained
      from the genital mucosa of a female red deer was characterised by sequencing and
      restriction endonuclease analyses as a cervid herpesvirus 1 closely related to
      Scottish Banffshire 82 strain.

PMID- 20031458
TI  - Cryogenic receive coil and low noise preamplifier for MRI at 0.01T.
AB  - We have investigated the design and construction of liquid nitrogen cooled
      surface coils made from stranded (litz) copper wire for low field MRI
      applications. If designed correctly, cooled litz coils can provide a competitive
      alternative to high temperature superconducting (HTS) coils without the
      complications associated with flux trapping. Litz coils can also be produced with
      a wider range of shapes and sizes, and at lower cost. Existing models were
      verified experimentally for flat spiral coils wound from solid and litz wires,
      operated at room temperature and 77K, and then used to design and optimise a
      cooled receive coil for MRI at 0.01T (425 kHz). The Q-factor reached 1022 when
      the coil was cooled to 77K, giving a bandwidth of just 0.42 kHz, so a low noise
      JFET preamplifier was developed to provide active damping of the coil resonance
      and thus minimise image intensity artefacts. The noise contribution of the
      preamplifier was determined using a method based on resistive sources and image
      noise analysis. The voltage and current noise were measured to be 1.25 nV/Hz(1/2)
      and 51 fA/Hz(1/2), respectively, and these values were used to estimate a noise
      figure of 0.32 dB at the resonant frequency of the cooled coil. The coil was used
      to acquire 0.01T spin echo images, first at room temperature and then cooled to
      77K in a low noise liquid nitrogen cryostat. The measured SNR improvement on
      cooling, by a factor of 3.0, was found to correspond well with theoretical
      predictions.

PMID- 20031459
TI  - Field strength dependence of PRESS timings for simultaneous detection of
      glutamate and glutamine from 1.5 to 7T.
AB  - An optimization of the PRESS sequence for magnetic resonance spectroscopy is
      presented to simultaneously detect the important brain metabolites of glutamate
      (Glu) and glutamine (Gln) at field strengths of 1.5, 3, 4.7, and 7T. Standard,
      clinical examinations typically use short echo times which in general are not
      ideal for the separation of Glu and Gln. The optimization procedure is based on
      numerical product operator simulations to produce yield and overlap measurements
      for all possible practical choices of PRESS inter-echo timings. The simulations
      illustrate the substantial modulations in Glu and Gln with field strength. At all
      field strengths, the optimized timings demonstrate a significant reduction in
      overlap compared to short echo PRESS, while maintaining a high metabolite signal,
      with Glu and Gln yields >90% when excluding T2 relaxation losses. Minimal overlap
      was attained at 7T (0.3% Gln contamination in the Glu signal), and 4.7T (1.2%).
      The optimized timings were applied in vivo on healthy volunteers at field
      strengths of 1.5 and 4.7T.

PMID- 20031460
TI  - Guidelines for the use of band-selective radiofrequency pulses in hetero-nuclear
      NMR: example of longitudinal-relaxation-enhanced BEST-type 1H-15N correlation
      experiments.
AB  - Band-selective radiofrequency (rf) pulses provide powerful spectroscopic tools
      for many biomolecular NMR applications. Band-selectivity is commonly achieved by
      pulse shaping where the rf amplitude and phase are modulated according to a
      numerically optimized function. This results in complex spin evolution
      trajectories during the pulse duration. Here we introduce simplified
      representations of a number of shaped pulses, commonly used in biomolecular NMR
      spectroscopy. These simple schemes, consisting in a suite of free evolution
      delays and ideal rf pulses, reproduce astonishingly well the effect on a scalar
      coupled hetero-nuclear two-spin system. As a consequence, optimal use of such
      pulse shapes in complex multi-pulse sequences becomes straightforward, as
      demonstrated here for the example of longitudinal-relaxation-enhanced BEST-HSQC
      and BEST-TROSY experiments. Applications of these optimized pulse sequences to
      several proteins in the size range of 8-21 kDa are shown.

PMID- 20031461
TI  - Coordinated increase in skeletal muscle fiber area and expression of IGF-I with
      resistance exercise in elderly post-operative patients.
AB  - Hypertrophy of developing skeletal muscle involves stimulation by insulin-like
      growth factor-I (IGF-I), however, the role of IGF-I in adult muscle is less
      clarified. In the present study, the mRNA splice variants of IGF-I (IGF-IEa and
      MGF) and the changes in muscle fiber cross sectional area after 12 weeks of
      training were studied in elderly post-operative patients. About 28 subjects, 14
      men and 14 women (age 69, range 60-86 years) were randomized to unilateral
      resistance training (RT: 3/week), electrical stimulation (ES: 1h/day) or
      functional exercises (FE: 1h/day). The non-operated-side served as a within
      subject control. Muscle biopsies were obtained from the vastus lateralis of both
      limbs at +2d post-operative (baseline), at 5 weeks and 12 weeks post-surgery to
      analyze for changes in type 1 and type 2 muscle fiber area. Changes in expression
      levels of IGF-I mRNA isoforms were determined using real-time RT-PCR, normalized
      to the ribosomal protein large protein 0 (RPLP0) mRNA and presented relative to
      the control-side. At baseline there was no difference between the three groups in
      muscle fiber area or resting levels of IGF-IEa and MGF. RT resulted in a
      significant increase in muscle fiber area of type 1 (+17%, p<0.05) and type 2
      (+36%, p<0.05) parallel to an increase in the expression of IGF-IEa and MGF, in
      contrast to ES and FE. The present study demonstrates that resistance training
      initiated in the acute post-operative phase is highly effective in increasing
      mean fiber area and in addition induces marked increases in the expression of IGF
      I splice variants, supporting the idea that IGF-I is involved in regulating
      muscle hypertrophy.

PMID- 20031462
TI  - Chronic cardiac tamponade in a cat caused by an intrapericardial biliary cyst.
AB  - A 1-year-old domestic longhair cat presented to our hospital with a 4-month
      history of progressive exercise intolerance and coughing. Two-dimensional
      echocardiography confirmed the presence of an intrapericardial cyst and cardiac
      tamponade. Tamponade was relieved via percutaneous aspiration of the cyst. The
      cyst was surgically excised 4 days later, and histopathology was consistent with
      a biliary cyst. The cat's clinical signs completely resolved following surgery.

PMID- 20031463
TI  - The susceptibility to tigecycline of Acinetobacter spp. may vary depending on the
      methodology used.

PMID- 20031465
TI  - Prolidase deficiency: a rare aetiology of arthritis.

PMID- 20031464
TI  - The impact of pregnancy on rheumatoid arthritis outcome: the role of maternofetal
      HLA class II disparity.
AB  - OBJECTIVES: To investigate the influence of pregnancy and postpartum on
      rheumatoid arthritis (RA) course and the impact of maternofetal HLA class II
      disparity. METHODS: In 13 women with RA, disease activity was assessed
      prospectively, before and every three months throughout pregnancy and after
      delivery until one year in postpartum. The HLA class II disparity was evaluated
      by typing HLA-DRB1, DQB1 and DQA1 alleles by the PCR-SSOP for 12 couples mothers
      and babies. Furthermore, for three women, RA disease activity during a previous
      pregnancy was evaluated retrospectively and HLA typing was performed for the
      three children. RESULTS: The mean age of patients was 30+/-5 years. All women had
      successful pregnancy. During pregnancy, a favourable RA outcome was noted in
      62.5% of cases. Three patients were in remission after conception. Persistent
      disease activity was noted in 30% of cases. In postpartum, disease relapse
      occurred in 92% of cases at a mean delay of 80+/-63 days. Three women did not
      resume the initial modifying antirheumatic drugs (DMARDs) 12 months after
      delivery. For others, the mean delay was 6+/-3.5 months. There was no significant
      correlation between the clinicoradiological parameters and the RA outcome. We
      noted a tendency towards correlation between male newborns and an unfavourable RA
      outcome (p=0.059). A high degree of maternofetal disparity in HLA class II was
      seen in 73.5% of cases. We observed a more marked improvement in disease activity
      parameters in case of more than one disparity but without a significant
      statistical difference. CONCLUSION: A favourable RA outcome during pregnancy in
      about two-thirds of the cases and a frequent relapse after delivery were
      observed. RA activity improvement is more obvious at the end of pregnancy. A high
      degree of maternofetal HLA class II disparity seems to modulate RA disease
      activity.

PMID- 20031466
TI  - Vertebral osteitis adjacent to kyphoplasty.
AB  - Vertebroplasty and vertebral kyphoplasty are increasingly performed to treat
      vertebral fractures, most notably those related to osteoporosis. Adverse effects
      are uncommon and consist chiefly of cement leakage out of the vertebral body and
      of vertebral fractures adjacent to the treatment site. We report two cases of
      vertebral osteitis adjacent to vertebroplasty sites, in a 60-year-old woman and a
      79-year-old man. Kyphoplasty to treat an osteoporotic vertebral fracture was
      followed by acute pain with an inflammatory time pattern and laboratory evidence
      of inflammation. Time to symptom onset was 10 days and 45 days, respectively.
      Magnetic resonance imaging showed changes consistent with inflammation in an
      adjacent vertebra (low signal on T1 images, gadolinium enhancement, and high
      signal on T2 images). A biopsy of the lesion disclosed moderate nonspecific
      inflammation, with no microorganisms or evidence of malignancy. Both patients
      recovered slowly. The male patient experienced a fracture at the site of the
      lesion. Few cases of osteitis adjacent to kyphoplasty have been reported. The
      underlying pathophysiology may involve changes in vertebral loading and cement
      leakage into the intervertebral disk.

PMID- 20031467
TI  - New treatments for myeloma.
AB  - The management of multiple myeloma has benefited substantially from the
      introduction of three new drugs, namely, the proteasome inhibitor bortezomib and
      the immunomodulators thalidomide and lenalidomide. These drugs were initially
      shown to improve the outcome of advanced myeloma and were subsequently found to
      transform the treatment of patients with previously untreated myeloma. Melphalan
      and prednisone combined with thalidomide or bortezomib is the new treatment of
      reference for patients who are elderly or ineligible for intensification. The
      introduction of these new drugs into induction regimens, intensified conditioning
      regimens, and posttransplantation regimens may improve overall survival among
      young patients by increasing the rate and quality of the treatment responses.
      Although myeloma remains incurable, prolonged survival is now a reasonable
      objective.

PMID- 20031468
TI  - Effectiveness of a semi-intensive multidisciplinary outpatient rehabilitation
      program in chronic low back pain.
AB  - OBJECTIVES: To evaluate the efficacy of a semi-intensive multidisciplinary
      outpatient program complying with the requirements of the Belgian National
      Institute for Health and Disability Insurance and intended for patients with
      chronic low back pain. METHODS: We included 262 patients with nonspecific chronic
      low back pain, among whom 136 (73 women and 63 men) with a mean pain duration of
      11.3 years completed the outpatient program (36 sessions each lasting 2h). The
      program consisted of education about back-sparing techniques, interventions by an
      occupational therapist and psychologist, and physical reconditioning. Three
      sessions (sessions 1, 18, and 36) were used to evaluate pain intensity,
      functional impairment, kinesiophobia, cognitive knowledge, knowledge of
      appropriate spinal movement technique, and physical performance (trunk muscle
      strength and endurance, mobility of the pelvis and lumbar spine, and aerobic
      capacity). RESULTS: All study variables were significantly improved at study
      completion compared to baseline: pain intensity was decreased by 44%, functional
      impairment by 40%, and kinesiophobia by 11% whereas knowledge was improved by
      59%, back-sparing technique by 95%, trunk muscle strength by 40% on average,
      trunk extensor muscle endurance by 90%, mobility by 8%, and aerobic capacity by
      18%. CONCLUSIONS: A semi-intensive multidisciplinary outpatient program was
      beneficial in patients with chronic low back pain. Careful patient selection and
      increased patient involvement in the program may help to improve adherence.

PMID- 20031470
TI  - The social costs of digital ulcer management in sclerodema patients: an
      observational Italian pilot study.

PMID- 20031469
TI  - Prevalence and significance of MEFV gene mutations in a cohort of patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: Pyrin/marenostrin, an inhibitory regulator of inflammation, is
      encoded by MEditerranean FeVer (MEFV) gene. Mutations of this gene are the cause
      of familial Mediterranean fever (FMF). A connection between MEFV gene mutations
      and rheumatic diseases has been suggested. The aim of this study was to explore
      the frequency and clinical significance of MEFV gene mutations in a cohort of
      Turkish patients with rheumatoid arthritis (RA). METHODS: The study included 103
      patients with RA and 103 age-, sex- and origin-matched healthy controls (HC). In
      all participants, genomic DNA was isolated and genotyped using amplification
      refractory mutation system or restriction fragment length polymorphism for the
      eight MEFV gene mutations (E148Q, M694V, M694I, M680I, V726A, A744S, R761H, and
      P369S). In the RA group, disease activity was determined using the disease
      activity score-28 (DAS-28), and radiological damage was evaluated by the modified
      Larsen scoring method. RESULTS: Carrier rates of MEFV gene mutations were 26/103
      (25.2%) and 24/103 (23.3%) in the RA and HC groups, respectively (p>0.05, OR:
      0.9, 95% CI: 0.48-1.71). In the RA group, while deformed joint count was
      significantly higher in the mutation carrier group than those of the non-carrier
      group (p<0.05), the level of C-reactive protein, DAS-28 and modified-Larsen
      scores were slightly but not significantly higher in the carrier group.
      CONCLUSION: The results of this study suggest that MEFV gene mutations appear to
      be an aggravating factor for the severity of RA, and consequently, patients with
      RA might be screened for MEFV gene mutations in countries where FMF is frequent.
      Whether the searching of MEFV gene mutations in RA patients is cost-effective
      deserves further investigations.

PMID- 20031471
TI  - Complete resolution of universal calcinosis in a patient with juvenile
      dermatomyositis using pamidronate.
AB  - A 14-year-old girl with juvenile dermatomyositis developed extensive and
      debilitating calcinosis, unresponsive to colchicine, while muscle involvement
      subsided. Pamidronate (2mg/kg/year) produced dramatic improvement of pain and
      function within 2 months and calcinosis had completely resolved by 2 years. No
      new calcifications have been noted with a 5-year follow-up.

PMID- 20031472
TI  - [The use of the "spare-parts tissue bank" concept in emergency hand surgery].
AB  - INTRODUCTION: In the case of multidigital hand trauma, the tissue of the
      amputated parts can be used for the reconstruction of the defected tissue
      localized on the other fingers. PATIENTS AND METHODS: A series of seven patients
      has been reviewed in this paper; the authors illustrate the different
      possibilities of using the "spare-parts concept" in the emergency hand trauma
      surgery. RESULTS: The functional results are presented. DISCUSSION: The different
      techniques of reconstruction using the "spare-parts concept" are discussed.
      CONCLUSION: In the cases of multidigital lesions, the surgeon should choose the
      best opportunity to use the tissue of the amputated digits, or the non
      conservable ones, to reconstruct the neighboring preserved segments.

PMID- 20031473
TI  - Living in 'Birdsville': exploring the impact of neighbourhood stigma on health.
AB  - AIMS: The stigma of living in a disadvantaged area is a consistent theme in
      discussions with residents of neighbourhood renewal (NR) areas in Victoria,
      Australia. Despite this, stigma is rarely examined explicitly in studies of
      neighbourhood disadvantage and health. This study will address four questions:
      (1) How do residents of disadvantaged areas describe their experiences of
      neighbourhood stigma? (2) Do experiences of neighbourhood stigma vary within
      neighbourhoods? (3) Is neighbourhood stigma related to health? (4) Is the
      relationship between neighbourhood stigma and health explained by other social
      factors that may contribute to poorer health? DESIGN: Cross-sectional community
      interviews comparing people living in NR areas (n = 4029) to people living in
      other parts of the same local government areas (LGAs) (n = 1857). Recruitment was
      achieved using community interviewers in NR areas and stratified random sampling
      in LGAs. MAIN OUTCOME MEASURES: A neighbourhood stigma variable, self-reported
      health, and satisfaction with life. RESULTS: About half (47.7%) of residents
      living in NR neighbourhoods compared to 9.4% of residents living elsewhere in the
      same LGAs felt that their neighbourhoods did not have a good reputation in
      surrounding areas. In NR areas, reported neighbourhood stigma was higher among
      people born in a non-English speaking country, receiving benefits or pensions,
      educated above year 10, or who reported having a disability. Reported
      neighbourhood stigma decreased with age. Stigma was associated with being in
      fair/poor health status (OR = 1.33, 1.06-1.89) and life satisfaction (OR = 0.66,
      0.55-0.8). CONCLUSIONS: Neighbourhood stigma may be a useful addition to the
      portfolio of variables that describe 'place' and its relationship with health.

PMID- 20031476
TI  - Essential fatty acids for dry eye: A review.
AB  - PURPOSE: Dry eye is a common complaint often encountered in optometric practice.
      However, it is a difficult condition to treat as clinical signs do not always
      correlate with patient symptoms. Essential fatty acids (EFA), particularly omega
      3 EFA, may be effective in dealing with the underlying causes. METHODS: A
      literature review was carried out on the PubMed, ScienceDirect and Ovid
      databases. Searches included keywords such as 'dry eye', 'essential fatty acids'
      and 'nutrition' to find articles relating to the treatment of dry eye syndrome
      (DES) with omega-3 EFAs. RESULTS: Omega-3 and -6 EFAs need to be consumed
      together within a reasonable ratio to be effective. Currently, typical diets in
      developed countries lack omega-3 EFA and this results in an overexposure to omega
      6. Omega-3 supplementation has an anti-inflammatory effect, inhibiting creation
      of omega-6 prostaglandin precursors. Omega-3 EFAs also demonstrate anti
      inflammatory action in the lacrimal gland preventing apoptosis of the secretory
      epithelial cells. Supplementation clears meibomitis, allowing a thinner, more
      elastic lipid layer to protect the tear film and cornea. CONCLUSION: Dietary
      supplementation of omega-3 EFA has already proven to be effective in coronary
      heart disease and arthritis. Safety is not a concern as it works synergistically
      with omega-6 in the body. Evidence suggests that supplementation with omega-3 EFA
      may be beneficial in the treatment and prevention of DES.

PMID- 20031478
TI  - Excited-state proton transfer of 3-hydroxybenzoic acid and 4-hydroxybenzoic acid.
AB  - The excited-state proton transfer of 3-hydroxybenzoic acid and 4-hydroxybenzoic
      acid was studied by time-resolved laser-induced fluorescence spectroscopy with
      ultra-short laser pulses. The excited-state reactions were identified in aqueous
      media as a function of the pH value. Apart from the well-known inversion of the
      ordinary dissociation properties of these compounds, new species were found which
      exist only in the excited-state resulting from a temporal and reversible
      annihilation of the aromatic bond system. These species and their reaction
      mechanisms were detected by their absorption and fluorescence spectra.

PMID- 20031477
TI  - Genomic and expression plasticity of polyploidy.
AB  - Polyploidy or whole genome duplication (WGD) occurs throughout the evolutionary
      history of many plants and some animals, including crops such as wheat, cotton,
      and sugarcane. Recent studies have documented rapid and dynamic changes in
      genomic structure and gene expression in plant polyploids, which reflects genomic
      and functional plasticity of duplicate genes and genomes in plants. Common
      features of uniparental gene regulation and nonadditive gene expression in
      regulatory pathways responsive to growth, development, and stresses in many
      polyploids have led to the conclusion that epigenetic mechanisms including
      chromatin modifications and small RNAs play central roles in shaping molecular
      and phenotypic novelty that may be selected and domesticated in many polyploid
      plants and crops.

PMID- 20031479
TI  - Lanthanide complexes derived from hexadentate macrocyclic ligand: synthesis,
      spectroscopic and thermal investigation.
AB  - The lanthanide complexes derived from (3,5,13,15-tetramethyl 2,6,12,16,21-22
      hexaazatricyclo[15.3.I(1-17)I(7-11)]cosa-1(21),2,5,7,9,11(22),12,15,17,19-decane)
      were synthesized. The complexes were found to have general composition
      [Ln(L)X(2).H(2)O]X, where Ln=La(3+), Ce(3+), Nd(3+), Sm(3+) and Eu(3+) and
      X=NO(3)(-) and Cl(-). The ligand was characterized by elemental analyses, IR,
      Mass, and (1)H NMR spectral studies. All the complexes were characterized by
      elemental analyses, molar conductance measurements, magnetic susceptibility
      measurements, IR, Mass, electronic spectral techniques and thermal studies. The
      ligand acts as a hexadentate and coordinates through four nitrogen atoms of
      azomethine groups and two nitrogen of pyridine ring. The lanthanum complexes are
      diamagnetic while the other Ln(III) complexes are paramagnetic. The spectral
      parameters i.e. nephelauxetic ratio (beta), covalency factor (b(1/2)), Sinha
      parameter (delta%) and covalency angular overlap parameter (eta) have been
      calculated from absorption spectra of Nd(III) and Sm(III) complexes. These
      parameters suggest the metal-ligand covalent bonding. In the present study, the
      complexes were found to have coordination number nine.

PMID- 20031480
TI  - Synthesis, characterization and spectroscopic investigation of a novel
      phenylhydrazone Schiff base with solvatochromism.
AB  - A novel Schiff base of 4,5-diazafluorene-9-p-nitrophenylhydrazone (DAFND) has
      been synthesized and characterized. The crystal structures of DAFND and its
      analogue 4,5-diazafluorene-9-phenylhydrazone (DAFPD) were determined by single
      crystal X-ray diffraction method. X-ray analyses reveal that DAFPD comprise of a
      nonplanar molecule and all atoms of DAFND are essentially coplanar. The color of
      DAFND changes from brown to blue when heated, so called thermochromism and the
      spectroscopic properties of the two compounds are investigated by electronic
      absorption spectra, showing DAFND possess solvatochromism, while DAFPD does not
      have thermochromic and solvatochromic properties. The lambda(max) of DAFND within
      various pure solvents are different ranging from 370 nm in toluene to 614 nm in
      pyridine. The imaginable mechanisms of thermochromism and solvatochromism are
      proposed.

PMID- 20031481
TI  - Vibrational spectroscopy investigation using ab initio and density functional
      theory on 3'-chloropropiophenone and 3'-nitropropiophenone.
AB  - The FTIR and FT Raman spectra of 3'-chloropropiophenone and 3'-nitropropiophenone
      have been recorded in the regions 4000-400 and 3500-100 cm(-1) respectively. The
      optimized geometry, frequency and intensity of the vibrational bands of 3'
      chloropropiophenone and 3'-nitropropiophenone were obtained by ab initio and DFT
      levels of theory with complete relaxation in the potential energy surface using 6
      31G (d,p) basis set. A complete vibrational assignment aided by the theoretical
      harmonic frequency analysis has been proposed. The harmonic vibrational
      frequencies calculated have been compared with experimental FTIR and FT Raman
      spectra. The observed and the calculated frequencies are found to be in good
      agreement. The experimental spectra also coincide satisfactorily with those of
      theoretically constructed simulated spectrograms.

PMID- 20031482
TI  - Attitudes and behaviors related to the introduction of electronic health records
      among Austrian and German citizens.
AB  - BACKGROUND: Acceptance by citizens seems to be crucial for the future success of
      an electronic health record (EHR) in Germany and Austria. We analyzed citizens'
      knowledge and expectations about the concept and contents of an EHR. We also
      addressed possible fears and barriers, and we investigated desired EHR
      functionalities relevant to citizens in the Austrian and German population.
      METHODS: Standardized interviews of a convenience sample of 203 Austrian and 293
      German citizens recruited in two metropolises. RESULTS: Up to three-quarter of
      the interviewed citizens already collect and store medical documents at home,
      mostly in paper-based form. No respondents had already used an Internet-based
      personal health record. Between 80% and 90% of respondents were supportive of the
      idea of an electronic exchange of health-related data between health care
      providers as core functionality of an EHR. However, many respondents formulated
      concerns with regard to data protection and data security within an EHR. The EHR
      functionalities most supported by respondents included the electronic vaccination
      record, online information on doctors and hospitals, and the administration of
      appointments and reminders. CONCLUSION: The results indicate a generally positive
      attitude towards the EHR. However, the study shows that data protection is an
      issue for many citizens, and that despite strong media discussion, there are
      information deficits with regard to the national EHR initiatives.

PMID- 20031483
TI  - Reactivation of hepatitis B virus infection with persistently negative HBsAg on
      three HBsAg assays in a lymphoma patient undergoing chemotherapy.
AB  - In patients with occult hepatitis B virus (HBV) infection, acute exacerbation may
      occur when they become immunocompromised. Usually, these patients develop
      hepatitis B surface antigen (HBsAg) seroreversion during the flare. Here we
      report on a patient with occult HBV infection, who developed HBV exacerbation
      after chemotherapy for diffuse large B-cell lymphoma. The resurgence of HBV DNA
      preceded the elevation of liver enzymes for 20 weeks. Atypically, despite high
      viraemia, serological tests showed persistently negative HBsAg using three
      different sensitive HBsAg assays (i.e., Architect, Murex and AxSYM). On comparing
      the amino acid sequence of the index patient with the consensus sequence, five
      mutations were found at pre-S1, five at pre-S2 and twenty-three mutations at the
      S region. Six amino acid mutations were located in the 'a' determinant, including
      P120T, K122R, M133T, F134L, D144A and G145A. The mutants K122R, F134L and G145A
      in our patient have not been tested for their sensitivity to Architect and Murex
      assays by the previous investigators and might represent the escape mutants to
      these assays.

PMID- 20031484
TI  - Absence of human bocavirus from deceased fetuses and their mothers.
AB  - BACKGROUND: The human bocavirus (HBoV), a newly discovered parvovirus, is closely
      related to the bovine parvovirus and the canine minute virus, which are known to
      cause adverse pregnancy outcomes. Another human parvovirus, B19, can lead to
      fetal hydrops, miscarriage and intrauterine fetal death (IUFD). OBJECTIVES: To
      determine the prevalence of HBoV DNA in aborted fetuses and IUFDs. The HBoV
      serology of the mothers was also studied. STUDY DESIGN: We retrospectively
      studied all available fetuses (N=535) autopsied during 7/1992-12/1995, and 1/2003
      12/2005 in Helsinki, Finland. All available formalin-fixed paraffin-embedded
      fetal tissues - placenta, heart and liver - of 120 miscarriages, 169 IUFDs, and
      246 induced abortions were studied by quantitative PCR. We also measured the HBoV
      IgM and IgG antibodies in the corresponding maternal sera (N=462) mostly of the
      first trimester. The IgM-positive sera underwent HBoV PCR. RESULTS: None of the
      fetal tissues harbored HBoV DNA. A total of 97% (448/462) of the mothers were
      positive for IgG antibodies to HBoV, while only 0.9% (4/462) exhibited HBoV
      specific IgM antibodies without viremia or respiratory symptoms. One IgM-positive
      mother had an unexplained fetal loss. CONCLUSIONS: We did not find HBoV DNA in
      any of the deceased fetuses. Almost all pregnant women were HBoV-IgG positive.

PMID- 20031485
TI  - Fielders and batters are injured too: a prospective cohort study of injuries in
      junior club cricket.
AB  - Internationally, there is a lack of good quality, prospectively collected injury
      data reported for junior club cricketers. This study describes injury rates
      according to age level of play and playing positions in junior community-level
      club cricketers to identify priorities for prevention. A prospective cohort study
      was used to monitor injuries in 88 under 12 years (U12), 203 U14 and 120 U16
      players from the Ballarat Junior Cricket Association, Australia over the
      2007/2008 playing season. Injury rates were calculated per 1000 participations
      when batting, bowling or fielding in matches and training sessions. Injury rate
      ratios were used to compare rates across age levels of play and position of play.
      Overall, 47 injuries were reported. Injury rates increased with age level of play
      with only one U12 player injured. Match injury rates were 3.57 per 1000 U14
      participations versus 4.80 per 1000 U16 participations. Training injury rates
      were 4.20 per 1000 U14 participations versus 5.11 per 1000 U16 participations. On
      a proportionate basis, injuries occurred equally to fielders, batters and
      bowlers. There was a trend towards more injuries occurring while batting and
      fielding in matches, and more injuries occurring while bowling and batting during
      training sessions. In conclusion, injury rates in junior cricket players are low,
      but increase with age level of play. Unlike adult forms of the game, injuries
      occur to fielders and batters at least as frequently as to bowlers, indicating
      that preventive strategies need to be developed for all junior players and not
      just bowlers, as has been the focus previously.

PMID- 20031486
TI  - Developing c-MET pathway inhibitors for cancer therapy: progress and challenges.
AB  - Successfully developed target-based therapies have significantly changed cancer
      treatment. Among many targets, the c-MET receptor tyrosine kinase and its ligand
      hepatocyte growth factor have recently gained considerable attention. The c-MET
      pathway is dysregulated in most human malignancies, and regulates tumor
      formation, progression and dissemination, and numerous c-MET pathway inhibitors
      are currently being evaluated in the clinic. Although some studies have shown
      impressive evidence of antitumor activity, the data should be interpreted with
      caution because of the distinct properties of these agents and diverse patient
      populations studied. Furthermore, in tumor types where patients might benefit
      from c-MET inhibition, rational combination treatments might ultimately provide
      maximal clinical benefit. Here, we review the evidence linking c-MET activation
      to cancer, and discuss the latest progress, opportunities and challenges in the
      clinical development of c-MET pathway inhibitors.

PMID- 20031489
TI  - Use of Dermabond in cleft lip repair.

PMID- 20031487
TI  - The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit different
      substrate preferences from their Escherichia coli counterparts.
AB  - The DNA glycosylases that remove oxidized DNA bases fall into two general
      families: the Fpg/Nei family and the Nth superfamily. Based on protein sequence
      alignments, we identified four putative Fpg/Nei family members, as well as a
      putative Nth protein in Mycobacterium tuberculosis H37Rv. All four Fpg/Nei
      proteins were successfully overexpressed using a bicistronic vector created in
      our laboratory. The MtuNth protein was also overexpressed in soluble form. The
      substrate specificities of the purified enzymes were characterized in vitro with
      oligodeoxynucleotide substrates containing single lesions. Some were further
      characterized by gas chromatography/mass spectrometry (GC/MS) analysis of
      products released from gamma-irradiated DNA. MtuFpg1 has substrate specificity
      similar to that of EcoFpg. Both EcoFpg and MtuFpg1 are more efficient at removing
      spiroiminodihydantoin (Sp) than 7,8-dihydro-8-oxoguanine (8-oxoG). However,
      MtuFpg1 shows a substantially increased opposite base discrimination compared to
      EcoFpg. MtuFpg2 contains only the C-terminal domain of an Fpg protein and has no
      detectable DNA binding activity or DNA glycosylase/lyase activity and thus
      appears to be a pseudogene. MtuNei1 recognizes oxidized pyrimidines on both
      double-stranded and single-stranded DNA and exhibits uracil DNA glycosylase
      activity. MtuNth recognizes a variety of oxidized bases, including urea, 5,6
      dihydrouracil (DHU), 5-hydroxyuracil (5-OHU), 5-hydroxycytosine (5-OHC) and
      methylhydantoin (MeHyd). Both MtuNei1 and MtuNth excise thymine glycol (Tg);
      however, MtuNei1 strongly prefers the (5R) isomers, whereas MtuNth recognizes
      only the (5S) isomers. MtuNei2 did not demonstrate activity in vitro as a
      recombinant protein, but like MtuNei1 when expressed in Escherichia coli, it
      decreased the spontaneous mutation frequency of both the fpg mutY nei triple and
      nei nth double mutants, suggesting that MtuNei2 is functionally active in vivo
      recognizing both guanine and cytosine oxidation products. The kinetic parameters
      of the MtuFpg1, MtuNei1 and MtuNth proteins on selected substrates were also
      determined and compared to those of their E. coli homologs.

PMID- 20031488
TI  - Simultaneous analysis of ochratoxin A and its major metabolite ochratoxin alpha
      in plasma and urine for an advanced biomonitoring of the mycotoxin.
AB  - Ochratoxin A (OTA) is a frequent mycotoxin contaminant found worldwide in foods
      and feedstuffs. Biomonitoring has been used to assess internal OTA exposure
      resulting from dietary intake and from other sources. Mycotoxin levels in blood
      and/or urine provide good estimates of past and recent exposure since OTA binds
      to serum proteins and is also partly excreted via the kidney. But, measuring OTA
      alone does not reflect its biotransformation. In light of scarce data on its
      metabolites in humans, it was the aim of this study to develop a method that
      allows analysis of OTA and its detoxication product ochratoxin alpha (OTalpha) in
      urine and in blood plasma. The method involves enzymatic hydrolysis of
      conjugates, liquid-liquid extraction, and analysis of sample extracts by liquid
      chromatography with fluorescence detection. Application of the validated method
      in a pilot study with 13 volunteers revealed the presence of OTA and OTalpha in
      all samples (limit of quantification: 0.05 ng/mL in urine, and 0.1 ng/mL in
      plasma). In line with negative findings of others, an OTA glucuronide was not
      detected, neither in urine nor in plasma. By contrast, conjugates of OTalpha
      (glucuronide and/or sulfate) are major products in these samples. This was
      confirmed by mass spectrometry detection. As OTalpha represents a large fraction
      of ingested mycotoxin, we propose to include analyses of this metabolite in
      future biomonitoring studies, also in light of the observed variations for urine
      OTalpha-levels that suggest different interindividual abilities for OTA
      detoxification in humans.

PMID- 20031490
TI  - A pilot application of image-guided navigation system in mandibular angle
      reduction surgery.

PMID- 20031494
TI  - High-accuracy sub-pixel motion estimation from noisy images in Fourier domain.
AB  - In this paper, we propose a new method for estimating sub-pixel motion via
      exploiting the principle of phase correlation in the Fourier domain. The method
      is based on linear weighting of the height of the main peak on the one hand and
      the difference between its two neighboring side-peaks on the other. Using both
      synthetic and real data we show that the proposed method outperforms many
      established approaches and achieves improved accuracy even in the presence of
      noisy samples.

PMID- 20031496
TI  - Projective nonnegative graph embedding.
AB  - We present in this paper a general formulation for nonnegative data
      factorization, called projective nonnegative graph embedding (PNGE), which 1)
      explicitly decomposes the data into two nonnegative components favoring the
      characteristics encoded by the so-called intrinsic and penalty graphs ,
      respectively, and 2) explicitly describes how to transform each new testing
      sample into its low-dimensional nonnegative representation. In the past, such a
      nonnegative decomposition was often obtained for the training samples only, e.g.,
      nonnegative matrix factorization (NMF) and its variants, nonnegative graph
      embedding (NGE) and its refined version multiplicative nonnegative graph
      embedding (MNGE). Those conventional approaches for out-of-sample extension
      either suffer from the high computational cost or violate the basic nonnegative
      assumption. In this work, PNGE offers a unified solution to out-of-sample
      extension problem, and the nonnegative coefficient vector of each datum is
      assumed to be projected from its original feature representation with a universal
      nonnegative transformation matrix. A convergency provable multiplicative
      nonnegative updating rule is then derived to learn the basis matrix and
      transformation matrix. Extensive experiments compared with the state-of-the-art
      algorithms on nonnegative data factorization demonstrate the algorithmic
      properties in convergency, sparsity, and classification power.

PMID- 20031495
TI  - A motion-aligned auto-regressive model for frame rate up conversion.
AB  - In this paper, a motion-aligned auto-regressive (MAAR) model is proposed for
      frame rate up conversion, where each pixel is interpolated as the average of the
      results generated by one forward MAAR (Fw-MAAR) model and one backward MAAR (Bw
      MAAR) model. In the Fw-MAAR model, each pixel in the to-be-interpolated frame is
      generated as a linear weighted summation of the pixels within a motion-aligned
      square neighborhood in the previous frame. To derive more accurate interpolation
      weights, the aligned actual pixels in the following frame are also estimated as a
      linear weighted summation of the newly interpolated pixels in the to-be
      interpolated frame by the same weights. Consequently, the backward-aligned actual
      pixels in the following frame can be estimated as a weighted summation of the
      corresponding pixels within an enlarged square neighborhood in the previous
      frame. The Bw-MAAR is performed likewise except that it is operated in the
      reverse direction. A damping Newton algorithm is then proposed to compute the
      adaptive interpolation weights for the Fw-MAAR and Bw-MAAR models. Extensive
      experiments demonstrate that the proposed MAAR model is able to achieve superior
      performance than the traditional frame interpolation methods such as MCI, OBMC,
      and AOBMC, and it is even better than STAR model for the most test sequences with
      moderate or large motions.

PMID- 20031497
TI  - Conjoint analysis for evaluating parameterized gamut mapping algorithms.
AB  - We show that conjoint analysis, a popular multi-attribute preference assessment
      technique used in market research, is a well suited tool to evaluate a multitude
      of gamut mapping algorithms simultaneously. Our analysis is based on data from
      psycho-visual tests assessed in a laboratory and in a web environment. Conjoint
      analysis allows us to quantify the contribution of every single parameter value
      to the perceived value of the algorithm; it also allows us to test the influence
      of additional parameters like gamut size or color shifts. We show that conjoint
      analysis can be individualized to images or observers if enough data is
      available. Especially promising in this respect is the combination of individual
      and population data.

PMID- 20031498
TI  - Wavelet steerability and the higher-order Riesz transform.
AB  - Our main goal in this paper is to set the foundations of a general continuous
      domain framework for designing steerable, reversible signal transformations
      (a.k.a. frames) in multiple dimensions ( d >or= 2). To that end, we introduce a
      self-reversible, Nth-order extension of the Riesz transform. We prove that this
      generalized transform has the following remarkable properties: shift-invariance,
      scale-invariance, inner-product preservation, and steerability. The pleasing
      consequence is that the transform maps any primary wavelet frame (or basis) of
      [Formula: see text] into another "steerable" wavelet frame, while preserving the
      frame bounds. The concept provides a functional counterpart to Simoncelli's
      steerable pyramid whose construction was primarily based on filterbank design.
      The proposed mechanism allows for the specification of wavelets with any order of
      steerability in any number of dimensions; it also yields a perfect reconstruction
      filterbank algorithm. We illustrate the method with the design of a novel family
      of multidimensional Riesz-Laplace wavelets that essentially behave like the N th
      order partial derivatives of an isotropic Gaussian kernel.

PMID- 20031499
TI  - Steerable weighted median filters.
AB  - A filter is steerable if transformed (i.e., rotated, scaled, etc.) versions of
      its impulse response can be expressed as linear combinations of a fixed set of
      basis functions. Steerability is important for numerous image processing
      applications. However, it is a property presently shared only by a specific class
      of linear filters. On the other hand, several classes of nonlinear filters, such
      as weighted median filters (WMFs), may offer certain advantages over linear
      filters such as robustness and edge preserving capabilities. In this paper, the
      concept of steerability is extended to encompass WMFs. It will be shown that, in
      general, a steerable WMF design technique needs to be capable of handling
      negative weights. Although methods that allow the design of WMFs admitting
      negative weights have already been proposed, such methods do not necessarily
      produce filters that are steerable, as opposed to the approach presented in this
      work. Experimental results illustrate the applicability of steerable WMFs in two
      applications, namely edge detection and orientation analysis.

PMID- 20031500
TI  - Learning with l1-graph for image analysis.
AB  - The graph construction procedure essentially determines the potentials of those
      graph-oriented learning algorithms for image analysis. In this paper, we propose
      a process to build the so-called directed l1-graph, in which the vertices involve
      all the samples and the ingoing edge weights to each vertex describe its l1-norm
      driven reconstruction from the remaining samples and the noise. Then, a series of
      new algorithms for various machine learning tasks, e.g., data clustering,
      subspace learning, and semi-supervised learning, are derived upon the l1-graphs.
      Compared with the conventional k-nearest-neighbor graph and epsilon-ball graph,
      the l1-graph possesses the advantages: (1) greater robustness to data noise, (2)
      automatic sparsity, and (3) adaptive neighborhood for individual datum. Extensive
      experiments on three real-world datasets show the consistent superiority of l1
      graph over those classic graphs in data clustering, subspace learning, and semi
      supervised learning tasks.

PMID- 20031501
TI  - Attack and flee: game-theory-based analysis on interactions among nodes in
      MANETs.
AB  - In mobile ad hoc networks, nodes have the inherent ability to move. Aside from
      conducting attacks to maximize their utility and cooperating with regular nodes
      to deceive them, malicious nodes get better payoffs with the ability to move. In
      this paper, we propose a game theoretic framework to analyze the strategy
      profiles for regular and malicious nodes. We model the situation as a dynamic
      Bayesian signaling game and analyze and present the underlining connection
      between nodes' best combination of actions and the cost and gain of the
      individual strategy. Regular nodes consistently update their beliefs based on the
      opponents' behavior, while malicious nodes evaluate their risk of being caught to
      decide when to flee. Some possible countermeasures for regular nodes that can
      impact malicious nodes' decisions are presented as well. An extensive analysis
      and simulation study shows that the proposed equilibrium strategy profile
      outperforms other pure or mixed strategies and proves the importance of
      restricting malicious nodes' advantages brought by the flee option.

PMID- 20031502
TI  - Electroencephalographic changes in pyridoxine-dependant epilepsy: new
      observations.
AB  - OBJECTIVE: Pyridoxine-dependent epilepsy (PDE) is a rare disease, of which the
      EEG manifestations are only partially characterised. We report our observations
      of EEG recordings in four patients with PDE. MATERIALS AND METHODS: EEG tracings
      from four patients fulfilling the clinical criteria for PDE were reviewed.
      Relative to the time of treatment with pyridoxine, EEG recordings were available
      before treatment in two patients (at ages four and 10 months), immediately after
      treatment in two patients and during long-term follow-up with treatment in all
      four patients. RESULTS: Pre-pyridoxine interictal EEG findings included: diffuse
      slowing, bilateral independent multifocal epileptiform discharges, generalized
      bursts of polyspike slow waves and focal or generalized sharp waves. In addition,
      the EEG was often asymmetrical and included: generalized semi-rhythmic sharp and
      slow waves, a burst suppression pattern and continuous generalized spike and slow
      waves. In one patient, who was followed subsequently, a decrease in multifocal
      spikes and sharp waves and permanent cessation of clinical seizures, within 10
      minutes of concurrent reduction of spikes in the pre-existing generalized spike
      slow wave pattern, was observed immediately after pyridoxine treatment. However,
      despite the clinical response in this patient we observed persistent generalized
      burst suppression for four days, and fluctuation of the EEG with diffuse slowing
      on day four and transient exacerbation of discharges with continuous spike slow
      waves on day 22. This was followed by intermittent sharp waves at eight and 20
      months, mild slowing at 31 months and normal EEG at 43 months. Long-term EEG
      findings in the other three patients receiving pyridoxine ranged between normal
      and intermittent multifocal sharp waves. CONCLUSION: Our data confirm previous
      observations and provide the following new findings: (1) the presence of burst
      suppression pattern after cessation of seizures can occur for up to five days
      after initiation of pyridoxine and should not exclude the diagnosis of PDE, (2)
      possible fluctuation and even transient worsening of electrographic discharges
      were observed for up to three weeks after initiation of pyridoxine and (3) the
      abnormal EEG can persist for up to 43 months before normalizing (range 1-43
      months) and in other cases in which it continues to be abnormal it may still
      improve after increasing the dose of pyridoxine.

PMID- 20031503
TI  - [Radiation therapy and medical imaging].
AB  - The goal of radiation therapy is to deliver a high-dose of radiation to the
      tumour or target region to improve local control of disease and a low-dose to
      normal soft tissues to limit side effects. Conformal radiation therapy, intensity
      modulated radiotherapy (IMRT), brachytherapy and stereotactic radiosurgery have
      been developed to achieve the desired dose distribution. They require precise
      imaging of internal anatomy so that it is well adapted to the tumour and organs
      at risk. Indeed, morphological imaging such as computed tomography is already
      recommended for radiotherapy planning. But radiation oncologists are also
      considering other imaging modalities for treatment planning and imaging tools
      capable of controlling patient motion during treatment. The aim of this article
      is to present and illustrate the place of imaging during treatment planning and
      delivery via techniques such as: 4D computed tomography, morphological and
      functional MRI, positron emission tomography, and imaging devices mounted on
      accelerators.

PMID- 20031504
TI  - [Psychology and neuropsychology of aging].

PMID- 20031505
TI  - [Identity and aging: psychosocial approaches].
AB  - This review is devoted to the notion of identity with regard to the process of
      aging from various approaches in social sciences. Continuity or transformation of
      identity is challenged in advanced age according to the place reserved in the
      society for the elderly subjects and their social age groups. Study methods are
      discussed in relation with the theoretical models, and their relevance to address
      aging people singularity and influence of environment. Changes of identity among
      elderly subjects appear to proceed in two ways. In the first one, called
      "rebirth", they establish a new self. In the second way, termed "turning point",
      better strategy for coping the aging effects is obtained by revealing untapped
      dimensions of the Self.

PMID- 20031506
TI  - [Unawareness in brain disorders: a complex and multifaceted phenomenon].
AB  - Unawareness of the diseases or its consequences can be a protective mechanism
      against a traumatic event. However, it can also result in dangerous behaviors and
      hamper the care management. Still not well understood, unawareness is a very
      complex and multidimensional construct involving neurological,
      neuropsychological, psychopathological and psychosocial dimensions. Sometimes
      considered to be a categorical phenomenon, unawareness is actually partial and
      dimensional. Nevertheless, no or only weak correlation are found between the
      results of various methods used to its assessment. We propose that the usual
      opposition between neurological (anosognosia) and psychopathological (denial)
      conceptions should be replaced by an integrative approach of the various
      dimensions involved in unawareness to allow a better adaptation of the care
      management.

PMID- 20031507
TI  - [Systemic family therapy in the context of Alzheimer's disease: a theoretical and
      practical approach].
AB  - Alzheimer's disease has a negative impact on family relationships and may trigger
      conflicts between the main caregiver and other family members. The systemic
      approach evidences the impact of dementia on structural and functional
      characteristics of the family system. Systemic family therapy is especially
      indicated in crisis situations such as emergency hospitalization or
      institutionalization of the patient, and when the family members do not agree on
      when and how to introduce care and support services at the patient's home. In
      this case, the aim of the intervention is to restore the communication between
      all the family members in order to find an agreement for the best management of
      the patients. Since September 2006, systemic family therapy has been offered in
      the memory clinic of the Broca Hospital to families having a member suffering
      from Alzheimer's disease. The involvement of the families was accomplished by the
      direct participation of the patient, main caregiver (spouse), grown-up children
      and grandchildren. The aim was to obtain an agreement for the access of support
      and care services at home from all the family members. The intervention was based
      on a step-by-step procedure and comprehended five sessions. The primary results
      of a pilot study are presented.

PMID- 20031508
TI  - [Strategy and methods of cognitive rehabilitation in patients with Alzheimer's
      disease or other dementia].
AB  - Individual cognitive rehabilitation of patients with Alzheimer's disease or other
      dementia is based on two principles: the understanding of the cognitive
      symptomatology (that is of the preserved and altered capacities) and the
      therapeutic contract, that sets the patient in the patient's center of the
      therapy. Therapy should be individualised, using facilitation techniques of
      learning or relearning and external assistance, to improve the quality of life
      and autonomy of the patients in the early stages of the disease. With the
      progression of dementia, the therapist, who has a cognitive and human knowledge
      of the patient, may continue to help the patient even if the objectives are not
      cognitive anymore.

PMID- 20031509
TI  - [Spaced-retrieval in patients with Alzheimer's disease. Critical review and
      clinical applications].
AB  - Memory deficit is the most common and invalidating cognitive impairment in
      subjects with Alzheimer's disease (AD). So far, pharmacological treatment shows
      little efficacy on the memory deficits. Recent studies have shown that specific
      cognitive remediation techniques can help compensating for memory deficits in AD
      dementia, even in advanced stages. Spaced retrieval is a technique based on
      recalling information over progressively longer intervals of time. It helps the
      patients with dementia learning and memorizing new information and is
      particularly suited for activities of daily life improvement. This paper first
      review the efficacy of this method in different types of dementia and more
      specifically in Alzheimer's disease; second, the cognitive mechanisms underlying
      spaced retrieval and the cognitive and clinical factors determining its efficacy
      are presented. Then the advantages and feasibility of the spaced retrieval
      technique in common clinical practice are discussed, and specific recommendations
      are given.

PMID- 20031510
TI  - [Assessment of episodic memory in illiterate elderly].
AB  - Assessing cognitive functions in illiterate people is a difficult task because
      most of the neuropsychological tests exploring episodic memory have been
      validated in formally educated people, are based on verbal material and,
      therefore, require a good knowledge of language. Two episodic memory tests (TNI93
      and TMA93) designed to be used for cognitive impairment screening in illiterate
      people have been designed, then validated in a multicultural low-educated
      population. Four hundred and thirty seven subjects aged 60 and over, living in
      the Seine-Saint-Denis district, received a medical check up offered by the
      National Health Service and their episodic memory performance was examined with
      these screening tests. The performance obtained on these tests depends both on
      age and educational level, as expected. Normative data for screening purpose in
      population with low education and/or not fluent with the language of the examiner
      are presented.

PMID- 20031512
TI  - [Eye disease in children aged 6 to 15 years: a hospital-based study in Yaounde].
AB  - This prospective study was conducted in the ophthalmology department of the
      Gynaeco-Obstetric and Paediatric Hospital in Yaounde and included 422 children
      recruited from January to April 2008. The aim was to identify the eye diseases
      seen frequently seen in school-aged children from 6 to 15 years and examine their
      epidemiological characteristics. RESULTS AND DISCUSSION: The study group included
      201 boys and 221 girls, with a mean age of 10,3 +/- 3.2 years. The most frequent
      disease was ametropia (refractive errors, 43.1%), including hyperopia, which had
      a prevalence of 23.7% Conjunctival disorders came next, accounting for 33%, more
      than half due to tropical endemic limbo conjunctivitis (17.8%). Binocular
      blindness affected 0.9% (n = 4), and low vision 0.7% (n = 3). CONCLUSION: This
      study, the first in its kind for the age group of 6-15 years in a developing
      country, allowed us to identify refractive errors as the principal complaint in
      consultations and led us to propose a reinforcement of screening in schools.

PMID- 20031511
TI  - [Acute accidental poisoning in children: aspects of their epidemiology,
      aetiology, and outcome at the Charles de Gaulle Paediatric Hospital in
      Ouagadougou (Burkina Faso)].
AB  - Accidents are a daily concern in the paediatric ward because of their frequency,
      diversity and severity. Acute accidental poisoning (AAP) accounts for an
      important portion of these. To help improvement management of AAP, we conducted a
      retrospective study covering a period of 2 years from January 2005 to December
      2006 at Charles de Gaulle Paediatric University Hospital in Ouagadougou. Of 9390
      admissions during the study period, 123 children, or 1.3%, were admitted for
      poisoning. A cumulative average of 11 were admitted monthly, with a peak of 16
      patients in April 2005 and 2006, together. AAP was most common among children
      aged 1 to 4 years. Their mean age was 3 years and ranged from 6 days to 12 years.
      Boys outnumbered girls, with a sex ratio of 1.2. Mothers of more than half (61%)
      of the children poisoned worked in the home. Household products accounted for
      44.7% of AAPs, followed by drug (22.7%) and food (22%) poisoning. Kerosene and
      other petroleum products topped the list of household products, with 54.5%.
      Tranquilizers (46.4%) and dairy products (37%) dominated the drug and food
      poisoning categories. Immediate outcome was fatal in 3% of cases, and three
      quarters of these deaths occurred during drug poisoning of children aged 1 to 4
      years. The mean hospital stay was 2 days, and ranged from 0 to 9 days. Health
      officials, the media, and community outreach must all help to increase awareness
      about the dangers of poisoning and of preventive measures.

PMID- 20031513
TI  - [Elevated C reactive protein rate in 23 black African patients with systemic
      lupus erythematosus and without opportunistic infectious disease].
AB  - INTRODUCTION: CRP rarely increases during systemic lupus exacerbations. MATERIALS
      AND METHODS: This retrospective study of patients with systemic lupus diagnosed
      according to ACR criteria examined all patients with no intercurrent infectious
      disease and responding to corticosteroid treatment and compared the patients with
      normal and with significantly elevated (> or = 30 mg/l) CRP. RESULTS: 23 black
      patients (22 women, 1 man) were selected and classified in two groups: group I
      with CRP > 30 mg/l (n = 12) and the controls, group II, with normal CRP (n =11).
      In group I, mean CRP was 279 mg/l. Four patients had isolated pericarditis, and
      one pericarditis associated with pleurisy. Nine patients had no cardiovascular
      risk factors or abnormal liver function enzymes. Antinuclear antibodies were
      specific for anti-DNA (n= 8), anti-Sm (n = 2), anti-RNP (n = 1), and anti-SSA (n
      = 1). In group II, seven patients had pericarditis, and nine had no
      cardiovascular risk factors or liver function results. Antinuclear antibodies
      were specific for anti-DNA (n = 9), anti-Sm (n = 1) and unknown (n = 1).
      DISCUSSION: The paucity of data about black Africans in the literature makes it
      difficult to interpret these results in terms of their specificity for this
      population or as a typical profile of elevated CRP without infectious disease.
      CONCLUSION: In absence of a specific profile for patients with elevated CRP
      without intercurrent infectious disease, we consider the possibility of a
      subgroup of the black population that may be particularly vulnerable and express
      CRP more easily.

PMID- 20031514
TI  - [Epidemiological, clinical and sociodemographic characteristics of human African
      trypanosomiasis (HAT) in and around Kinshasa, Democratic Republic of Congo].
AB  - BACKGROUND: Despite efforts to control human African trypanosomiasis (HAT) in the
      field, this infection remains prevalent in endemic or epidemic form in most of
      its traditional habitats. In the Democratic Republic of Congo (DRC), HAT has
      extended beyond rural areas to reach large cities such as Kinshasa. The objective
      of this study was to analyse the characteristics of trypanosomiasis patients
      (cases) in Kinshasa and to compare them to those of healthy controls. METHODS AND
      POPULATION OF STUDY: This case-control study allowed us to compare case patients
      and controls for some epidemiologic, clinical and sociodemographic
      characteristics. In all, 1764 people (588 case-patients and 1176 controls) were
      interviewed according to a structured questionnaire. Case-patients were infected
      with trypanosomiasis and entered the National Human African Trypanosomiasis
      Program (PNLTHA-DRC) from January 2004 through December 2005. Controls were
      matched for sex, age and residence to the corresponding case-patient, but had
      negative results from the Card Agglutination Trypanosomiasis Test (CATT-Test)
      whole-blood serologic analysis. Each patient was matched with two controls.
      RESULTS: Cases were identified in all 24 districts of Kinshasa, but were
      concentrated in the outskirts (outlying areas and southern expansion) and in
      rural areas. Overall, 25% (144/588) of case-patients lived in urbanized areas.
      People in the labour market (aged 20-49 years) were affected more often than
      others. HAT affected men and women equally. It also affected at higher rates
      people who moved around a lot and those who worked in rural or domestic
      activities, especially those in close contact with watercourses. Sleep disorders
      were the primary clinical sign (85%). Cervical adenopathies were observed
      frequently (66%). Fever was reported in 68% of case-patients. Most (73.5%) were
      diagnosed at a very advanced stage of infection (meningoencephalitic or
      neurological stage). CONCLUSION: These results highlight several modifiable or
      avoidable characteristics associated with HAT. Interventions on them might make
      it possible to reduce the morbidity and mortality rates associated with HAT and
      prevent wider extension of this disease.

PMID- 20031515
TI  - [The effectiveness of community volunteers in counting populations and assessing
      their nutritional vulnerability during armed conflict: district health in D.R.
      Congo, Central Africa].
AB  - The study assessed the ability of community volunteers, working with district
      health officials, to conduct a local census to count the population in their
      villages and assess their nutritional vulnerability. The study involved
      organizing community volunteers in village nutrition committee and assigning them
      to count the village population in a Kivu rural health district (D.R.Congo) and
      assess their vulnerability in terms of nutrition. The study took place in March
      and April 2003, during armed conflict in the region. Community volunteers
      supervised by district health officials collected data, presented here as median
      proportions (with their Max and Min), by age category. The results show that
      community volunteers were able to conduct this census with reliable results. The
      population distribution by age category was similar to the national model from a
      survey by experts. The community volunteers estimated a median of 22.2 % (6.2-100
      %) of households in each village in the eastern DR Congo were vulnerable and
      required foreign aid. Community volunteers can contribute accurately to the
      collection of demographic data to be used in health programme planning, thus
      allowing these data to be followed even during instability and armed conflicts.

PMID- 20031516
TI  - [Social anthropological approach to tuberculosis in Mopti (Mali): popular
      representations and use of treatment].
AB  - In Mali, there were 4508 new cases of tuberculosis in 2003, and 5222 in 2006.
      Tuberculosis (TB) is thus an important public health problem, decreasing the
      physical, financial and social capital of individuals, their families and
      society. Because responses to TB have not yet applied a sufficiently integrated
      approach that can improve patients' access to quality care, this FORESA project
      advocates a patient-centered approach. Before any intervention, FORESA thus
      sought to analyse the situation of TB in Mali and responses to it. The study aims
      to analyse the discourse about and popular representations of TB (its forms, its
      signs), the situations in which people are exposed to it or transmit it, and
      popular practices related to its prevention and the experience of having it. This
      qualitative, descriptive and analytical study includes a literature review, in
      depth interviews with opinion leaders, community health workers and TB patients,
      focus groups, and the observations of practices. The interviews were recorded,
      transcribed, and analysed. Subjects provided informed consent to participation.
      This study showed that: * the terms for TB in local languages (Bambara, Dogon and
      Fulfulde) include white cough, big cough, and long cough; * These communities
      differentiate between 2 main forms of cough (simple and wet); * TB is perceived
      as a transmissible disease, a disease of contact with a contaminated body or
      objects; * TB is seen as a serious, contagious, hereditary, shameful disease that
      may result from the transgression of social norms; * The prevention of TB
      consists of avoiding people who have the disease or transmitting factors; *
      Therapeutic remedies, in order, are self-medication, the use of traditional
      healers, and finally visits to health centres; * The population wants more
      information about TB and be involved in the fight against it. This study shows
      the many points of convergence about TB nosology, etiology and therapy between
      the Mopti population and other groups in Mali (including the Mande, Senoufo and
      Soso), between the population of Mali and some ethnic groups in Burkina Faso
      (such as the Dioula, Bobo, Tiefo Vigue), and between the population of Mali and,
      Burkina Faso and others in Africa (Gambia, Nigeria, South Africa, etc.). There is
      also a difference between popular knowledge about TB and biomedical knowledge.
      The population does not know that TB is transmitted mainly, even exclusively, by
      nasal droplets or that patients are no longer contagious after two weeks of
      treatment. The widespread dissemination of this information may have a positive
      effect, reducing stigmatization and improving access to treatment. Mali must
      strengthen the skills of all participants in the fight against tuberculosis, to
      strengthen their framework and to monitor and evaluate their activities.

PMID- 20031517
TI  - [Do commercial sex workers who discuss treatment with family and friends adhere
      to it better?].
AB  - INTRODUCTION: The number of HIV trials in Africa is increasing, and they target
      population groups with high HIV incidence, such as sex workers. Little
      information, however, is available about the adherence to long-term therapy among
      such marginalized groups with few economic resources and poor social and family
      support. A project called "Yerelon" ("know herself" in the Dioula language) began
      in 1998 in Bobo-Dioulasso to improve the health of women involved in commercial
      sex through STI/HIV prevention and care adapted to them. This study was conducted
      before introducing long-term treatment to the population, to assess the effect of
      communication with those around them on the capacity of these vulnerable women to
      adhere to drug prescriptions. METHODS: The study was based on interviews
      conducted during the pilot phase of a 3-month trial of vitamins with potential
      participants. It concerned two groups of women: one group was infected with HIV
      (N = 22), the other was not (N = 20); all women in both groups were infected by
      HSV-2, however. For 5 weeks, the two psychologists of the study team in charge of
      adherence assessment carried out weekly in-depth interviews with the
      participants. The qualitative data analysis was organised around several themes.
      The data were related to aspects of communication with family and friends,
      serologic results, and adherence. RESULTS: According to our definition of
      communication about treatment, 20 participants communicated with their family and
      friends; adherence was good for all but three of them. Women who reported that
      they were married or living with someone (7/42) nearly all spoke about the study
      treatment (06/07) with him. Of 16 participants living in a family, 10
      communicated with them about the treatment. On the other hand, as seems logical,
      single women who lived alone spoke less often about the treatment with family and
      friends (04/19). Talking about the treatment did not appear to involve the family
      or friends in the treatment; no one reminded any participant, whether she lived
      alone or in a family, to take her medicine. Nor did this discussion seem
      "helpful" to any of the women. Twenty-two participants hid the study treatment
      from family and friends; adherence was good for all but two of these. Social
      management of the treatment was related to HIV serologic status and relationships
      with family and friends. Concern about gossip about HIV status made it difficult
      to integrate the treatment into conversation. Those who did not agree to
      communicate with their family about the treatment did not even take the drug in
      the sight of the others. Sometimes, refusal to communicate was aimed at avoiding
      disapproval when the family did not have a favorable perception of prolonged
      treatment. Hiding the treatment was not an obstacle to good adherence. Adherence
      was related to perception of the treatment more than to communication about it.
      CONCLUSION: Adherence was similar in cases with and without communication. It
      appeared that these marginalized women, without social networks, were able to
      adhere correctly to a long-term treatment. To minimize the risks of non
      adherence, the support system planned must take into account the factors
      influencing perceptions of the drug. Specific psychological support centered on
      the relation with the drug appears necessary during treatment initiation and
      follow up.

PMID- 20031518
TI  - [Debate and challenges on the topic of free medical care in Africa: "Back to the
      Future"?].
AB  - In its 2008 annual report, WHO affirmed the importance of resisting the
      temptation to depend on direct payment for primary health care. Members of the
      WHO committee on the social determinants of health as well as of those at the
      conference on primary health care in Ouagadougou in 2008 reaffirmed the need to
      make access to health care systems more equitable. Several decades after
      imposition of direct payment began, convincing data clearly demonstrate its
      harmful effects on the basic fairness of access to care. Accordingly, the current
      debate in the field of financial support for health involves the elimination of
      payments. More precisely, we can finally say that this is a debate about a return
      to the free care that existed before the widespread implementation of "cost
      recovery" systems. Here we want to review these discussions and prepare the
      ground for a debate on possible effective strategies for making health care
      systems more equitable from the perspective of universal coverage. We will thus
      note that analyses today must certainly focus more on how to eliminate direct
      payments than on the reasons to do so, already amply demonstrated. The
      international community must now undertake to support governments that want to
      move in this direction and ensure that the process is thoroughly documented so
      that it can also produce useful knowledge for the formulation of fair public
      policies.

PMID- 20031520
TI  - [The first successful adult right-lobe living donor liver transplantation in
      Hungary].
AB  - The authors report on their experiences related to the first adult live donor
      liver transplantation performed in Hungary. The transplantation was done between
      brother and sister on 19th of November, 2007. The right lobe of the 33-year-old
      healthy male's donor liver (segments 5-8) was removed and implanted into the 23
      year-old female suffering from cirrhosis on the ground of autoimmune hepatitis.
      The implantation of the right liver lobe was done after own hepatectomy in
      orthotopic position. Liver function has improved rapidly following the
      transplantation. The donor was discharged on the 10th post-operative day with
      stable liver function. He had full rehabilitation, got back to work, and control
      check-ups showed a significant liver regeneration. Two years after
      transplantation, the recipient also lives an active life with compensated liver
      function and she is under regular medical check-up. With the case report, authors
      overview the indications and techniques of living donor right-lobe liver
      transplantation.

PMID- 20031521
TI  - [Links between diabetes mellitus and sleep disorders: focusing on obstructive
      sleep apnea].
AB  - During the past decades obesity and diabetes have become increasingly common in
      modern, industrialized societies. At the same time sleep disorders, chronic sleep
      loss and sleep deprivation have also become more and more prevalent. There may be
      a positive feed back circle between the two disorders: sleep problems may affect
      endocrine function and metabolic conditions, while metabolic abnormalities
      potentially interfere with sleep regulation. Sleep-disordered breathing,
      obstructive sleep apnea in particular, has the strongest association with glucose
      metabolism. Prevalence and severity of obstructive sleep apnea are higher among
      diabetic individuals compared to non-diabetic subjects. Central obesity is an
      important risk factor both in diabetes and sleep apnea, and recent evidence
      supports the direct association between them. Diabetic neuropathy and metabolic
      syndrome parameters correlate with the presence and severity of obstructive sleep
      apnea. Intermittent hypoxia may cause insulin resistance, consequently increasing
      the risk of diabetes and further impairing glycemic control. Specialists in both
      diabetology and sleep medicine need to work together to prevent the negative
      interactions between these two groups of disorders and to also preserve patients'
      quality of life and to improve outcomes.

PMID- 20031519
TI  - [Thromboembolism--risk, prevention and therapy. Practice Guideline].

PMID- 20031522
TI  - [Local control in breast cancer: constant importance, changing radiotherapy
      practice].
AB  - Local control is of primary importance when treating operable breast cancer.
      Local relapse serves as a secondary source of distant metastases, and compromises
      survival. Postoperative radiotherapy improves local control after mastectomy or
      breast conserving surgery, however, sometimes it leads to overtreatment. The risk
      of local relapse may be estimated based on different correlated factors, such as
      the type of the surgery, the size and stage of the tumor, the nodal status, the
      histological type, multifocality and biological features of the cancer, the
      margin status, the age and the mammographic appearance of the lesion. Late
      radiogenic sequelae appearing 5-10 years after radiotherapy are sometimes fatal,
      but may be prevented if radiotherapy is delivered at a high standard. Systemic
      therapies contribute to local control, and in some cases may substitute
      radiotherapy. In other low risk cases, radiotherapy may be either omitted or
      lessened. Local therapies in breast cancer should be tailored individually.

PMID- 20031523
TI  - [Protocol for the antiviral therapy of hepatitis B and D].

PMID- 20031524
TI  - [Mother-child agreement regarding the depressive symptoms and the quality of life
      of the child and its influencing factors in children with and without
      depression].
AB  - Mother-child agreement and influencing factors were studied in depressed and non
      depressed children. AIMS: We hypothesized that age and gender of the child and
      maternal depression influenced mother-child agreement; parents of depressed
      children underestimated the quality of life of their children; agreement was
      better in older and non-depressed children. METHODS: We studied depressed
      children with Major Depressive Disorder (n = 354, mean age = 11.69 +/- 2.05
      years), and non-depressed school-age children (n = 1695, mean age = 10.34 +/-
      2.19 years). Psychiatric diagnosis was obtained by a semi-structured interview;
      depressive symptoms and quality of life were measured by self-reported
      questionnaires. RESULTS: Mother-child agreement about depressive symptoms
      increased as children got older. Mother-son reports showed significant
      difference, mother-daughter reports were similar. Depressed mothers reported more
      serious symptoms for their children. Depressed children's parent rated lower
      quality of life than children for themselves. Agreement was influenced by
      depression of the child and only marginally by age. CONCLUSIONS: Age and
      psychiatric illness of the examined person influences agreement, which finding
      may well be important in practice.

PMID- 20031535
TI  - A dream, a journey, and a promise: the inauguration of Circulation:
      Cardiovascular Genetics.

PMID- 20031536
TI  - Genome-wide approaches to finding novel genes for lipid traits: the start of a
      long road.

PMID- 20031537
TI  - Blood and cardiovascular disease: the promise and limitations of gene expression
      analysis.

PMID- 20031538
TI  - Genome-wide association analysis of high-density lipoprotein cholesterol in the
      population-based KORA study sheds new light on intergenic regions.
AB  - BACKGROUND: High-density lipoprotein cholesterol (HDLC) is a strong risk factor
      for atherosclerosis and is assumed to be under considerable genetic control. We
      aimed to identify gene regions that influence HDLC levels by a genome-wide
      association analysis in the population-based KORA (Cooperative Health Research in
      the Region of Augsburg) study. METHODS AND RESULTS: In KORA S3/F3 (n=1643), we
      analyzed 377 865 quality-checked single-nucleotide polymorphisms (SNPs; 500K,
      Affymetrix, Santa Clara, Calif), complemented by the publicly available genome
      wide association results from the Diabetes Genetics Initiative (n=2631) and by
      replication data from KORA S4 (n=4037) and the Copenhagen City Heart Study
      (n=9205). Among the 13 SNPs selected from the KORA S3/F3 500K probability value
      list, 3 showed consistent associations in subsequent replications: 1 SNP 10 kb
      upstream of CETP (pooled probability value=8.5x10(-27)), 1 SNP approximately 40
      kb downstream of LIPG (probability value=4.67x10(-10)), both independent of
      previously reported SNPs, and 1 from an already reported region of LPL
      (probability value=2.82x10(-11)). Bioinformatical analyses indicate a potential
      functional relevance of the respective SNPs. CONCLUSIONS: The present genome-wide
      association study identified 2 interesting HDLC-relevant regions upstream of CETP
      and downstream of LIPG. This draws attention to the importance of long-range
      effects of intergenic regions, which have been underestimated so far, and may
      impact future candidate-gene-association studies toward extending the region
      analyzed. Furthermore, the present study reinforced CETP and LPL as HDLC genes
      and thereby underscores the power of this type of genome-wide association
      approach to pinpoint associations of common polymorphisms with effects explaining
      as little as 0.5% of the HDLC variance in the general population.

PMID- 20031539
TI  - Correlation of peripheral-blood gene expression with the extent of coronary
      artery stenosis.
AB  - BACKGROUND: The molecular pathophysiology of coronary artery disease (CAD)
      includes cytokine release and a localized inflammatory response within the vessel
      wall. The extent to which CAD and its severity is reflected by gene expression in
      circulating cells is unknown. METHODS AND RESULTS: From an initial coronary
      catheterization cohort we identified 41 patients, comprising 27 cases with
      angiographically significant CAD and 14 controls without coronary stenosis. Whole
      genome microarray analysis performed on peripheral-blood mononuclear cells
      yielded 526 genes with >1.3-fold differential expression (P<0.05) between cases
      and controls. Real-time polymerase chain reaction on 106 genes (the 50 most
      significant microarray genes and 56 additional literature genes) in an
      independent subset of 95 patients (63 cases, 32 controls) from the same cohort
      yielded 14 genes (P<0.05) that independently discriminated CAD state in a
      multivariable analysis that included clinical and demographic factors. From an
      independent second catheterization cohort, 215 patients were selected for real
      time polymerase chain reaction-based replication. A case:control subset of 107
      patients (86 cases, 21 controls) replicated 11 of the 14 multivariably
      significant genes from the first cohort. An analysis of the 14 genes in the
      entire set of 215 patients demonstrated that gene expression was proportional to
      maximal coronary artery stenosis (P<0.001 by ANOVA). CONCLUSIONS: Gene expression
      in peripheral-blood cells reflects the presence and extent of CAD in patients
      undergoing angiography.

PMID- 20031540
TI  - Association between the coronary artery disease risk locus on chromosome 9p21.3
      and abdominal aortic aneurysm.
AB  - BACKGROUND: Recent genome-wide studies have shown a significant association of a
      locus on chromosome 9p21.3 and coronary artery disease. We performed a case
      control study to investigate the association between this locus and abdominal
      aortic aneurysm (AAA). METHODS AND RESULTS: A total of 1714 patients (899
      patients with AAA and 815 controls) were genotyped for the lead single-nucleotide
      polymorphism, rs1333049, on chromosome 9p21. The frequency of the C (risk) allele
      of rs1333049 in the control group was 0.471. There was a significant association
      between the C allele and AAA (odds ratio, 1.22; 95% confidence interval, 1.06 to
      1.39; P=0.004). The genotypic-specific odds ratios (compared with the GG
      genotype) were 1.17 (95% confidence interval, 0.93 to 1.47; P=0.191) for the GC
      genotype and 1.50 (95% confidence interval, 1.14 to 1.97; P=0.004) for the CC
      genotype. In logistic regression modeling, the association of the CC genotype
      with AAA was independent of the presence of clinical coronary artery disease
      (odds ratio, 1.46; 95% confidence interval, 1.11 to 1.94; P=0.008). CONCLUSIONS:
      Our study shows that the recently identified chromosome 9 variant that increases
      risk of coronary artery disease is also associated with the presence of AAA. The
      findings suggest that the effect of this locus on risk of cardiovascular disease
      extends beyond the coronary circulation.

PMID- 20031541
TI  - Mutations in the HFE gene and cardiovascular disease risk: an individual patient
      data meta-analysis of 53 880 subjects.
AB  - BACKGROUND: Whether mutations in the hemochromatosis (HFE) gene increase
      cardiovascular disease risk is still undetermined. The main reason is the low
      frequency of the mutations, in particular of the compound C282Y/H63D genotype. We
      combined the data of 11 observational studies for an individual patient data meta
      analysis. METHODS AND RESULTS: Individual patient data were obtained from
      published as well as unpublished studies that had information available on the
      C282Y mutation as well as the H63D mutation in relation to coronary heart disease
      risk. Individual records were provided on each of the 53 880 participants in 11
      studies. In total, 10 541 patients with coronary events were documented, of whom
      5724 had an acute myocardial infarction. The crude and adjusted association
      between HFE genotypes and coronary events was examined by logistic regression
      analysis. We explored potential effect modification of the association between
      traditional cardiovascular risk factors and coronary events by HFE genotypes.
      After full adjustment, the odds ratio for coronary heart disease was 1.12 (95%
      CI, 0.92 to 1.37) for subjects with the compound heterozygous (C282Y/H63D)
      genotype relative to those with the wild-type/wild-type genotype. The odds ratios
      for C282Y/C282Y, C282Y/wild-type, H63D/H63D, and H63D/wild-type were 0.78 (95%
      CI, 0.49 to 1.26), 0.98 (95% CI, 0.90 to 1.07), 1.16 (95% CI, 0.97 to 1.38), and
      1.07 (95% CI, 1.00 to 1.14), respectively. There was no evidence for effect
      modification. CONCLUSIONS: The results of this large individual patient data meta
      analysis do not support the view that HFE gene mutations are associated with an
      increased risk of coronary heart disease or acute myocardial infarction.

PMID- 20031542
TI  - Cardiovascular genomics, personalized medicine, and the National Heart, Lung, and
      Blood Institute: part I: the beginning of an era.
AB  - The inaugural issue of Circulation: Cardiovascular Genetics arrives at a
      remarkable time in the history of genetic research and cardiovascular medicine.
      Despite tremendous progress in knowledge gained, cardiovascular disease(CVD)
      remains the leading cause of death in the United States,1 and it has overcome
      infectious diseases as the leading cause of death worldwide.2 In addition, rates
      of CVD remain higher in black and Hispanic populations in the United States.1 The
      recent Strategic Plan of the National Heart, Lung,and Blood Institute (NHLBI)
      emphasizes research areas to fill the significant knowledge gaps needed to
      improve the diagnosis,treatment, and control of known risk factors and clinically
      apparent disease. Simultaneously, the NHLBI Strategic Plan recognizes a
      tremendous opportunity that is available for use of genetic and genomic research
      to generate new knowledge that might reduce the morbidity and mortality from CVD
      in US populations.3 Public availability of vast amounts of detailed sequence
      information about the human genome, completed sequence data on dozens of other
      animal genomes, and private sector development of high-throughput genetic
      technologies has transformed in a few short years the conduct of cardiovascular
      genetics and genomics research from a primary focus on mendelian disorders to a
      current emphasis on genome-wide association studies (GWAS; Figure1). In this
      review, we describe the rationale for the current emphasis on large-scale genomic
      studies, summarize the evolving approaches and progress to date, and identify
      immediate-term research needs. The National Institutes of Health (NIH) and the
      NHLBI are supporting a portfolio of large-scale genetic and genomic programs in
      diverse US populations with the longer-term objective of translating knowledge
      into the prediction, prevention, and preemption of CVD, as well as lung, sleep,
      and blood disorders. Underlying this portfolio is a strong commitment to make
      available participant-level data and aggregate research results to the broad
      community of investigators, while protecting the privacy and confidentiality and
      respecting the informed consent of study participants.

PMID- 20031543
TI  - Metabolomics: ready for the prime time?
AB  - Metabolomics is one of the most rapidly growing areas of contemporary science.
      Although classic genetics aims to link variations in the DNA sequence directly to
      distinct phenotypes, "-omic" technologies allow us to shift the focus from the
      specific gene to the actual effects of the gene itself. Because neither the
      transcriptional or protein profile can be directly correlated with metabolite
      concentrations, the importance of measuring small-molecule metabolites has become
      increasingly clear. In view of the rapid progress in metabolomic techniques,
      metabolomics is expected to become more widely applied to cardiovascular
      research. Metabolomics brings the promise of the identification of potential
      biomarkers and alterations in biochemical pathways, which will facilitate the
      transition from a reductionistic approach to a more integrated science. Because
      the relative lack of attention given to the system behavior hampers our progress
      in translating basic science research into clinical applications,the holistic
      nature of these emerging techniques may yield valuable new strategies for the
      prevention and treatment of cardiovascular diseases. By analogy to the genome,
      the metabolome is defined as the total complement of small-molecule metabolites
      found in or produced by an organism. The most recent estimates place the number
      of endogenous metabolites (metabolites synthesized by enzymes encoded in the
      human genome) at approximately a few thousand, far less than had been previously
      predicted. Importantly, the size of the exogenous metabolome(metabolites not
      synthesized in the body but consumed as food or generated by host-specific
      microbes) is far greater,and there is often a spatial separation between
      metabolite synthesis and use. Hence, although genes, proteins, and metabolites
      are intimately connected in biological systems and their interactions with
      environmental changes are reflected in the metabolome, gene or protein expression
      may not directly correlate to metabolite concentrations from the same region
      (Figure 1). Thus, there is a clear need for an additional readout at the
      metabolite level, and the promise of "metabolomic profiling" is to achieve a
      quantitative and qualitative assessment of a subset of metabolites in complex
      samples such as bodily fluids and tissues.

PMID- 20031544
TI  - HapMap and mapping genes for cardiovascular disease.
AB  - A key goal of biomedical science is to understand why individuals differ in their
      susceptibility to disease. Family history is among the established risk factors
      for most forms of cardiovascular disease, in part because inherited DNA sequence
      variants play a causal role in disease susceptibility. Consequently, the search
      for these variants has intensified over the past decade. One class of DNA
      sequence variants takes the form of single nucleotide changes(single nucleotide
      polymorphisms, or SNPs), usually with two variants or alleles for each SNP. SNPs
      are scattered throughout the 23 pairs of chromosomes of the human genome, and
      roughly 11 million common polymorphisms (ie,those > 1% frequency) are estimated
      to exist. A combination of SNP alleles along a chromosome is termed a haplotype.
      The International Haplotype Map Project was designed to create a public genome
      wide database of common SNPs and, consequently, enable systematic studies of most
      common SNPs for their potential role in human disease. We review the following:
      (1) the concept of linkage disequilibrium orallelic association, (2) the HapMap
      project, and (3) several examples of the utility of HapMap data in genetic
      mapping for cardiovascular disease phenotypes.

PMID- 20031548
TI  - Paraoxonase and coronary heart disease risk: language misleads, linkage
      misinforms, function clarifies.

PMID- 20031549
TI  - Chromosome 9p21 and cardiovascular disease: the story unfolds.

PMID- 20031550
TI  - Common genetic variants in ANK2 modulate QT interval: results from the KORA
      study.
AB  - BACKGROUND: Spatial and timely variations in QT interval, even within its normal
      range, may underlie susceptibility to cardiac arrhythmias and sudden cardiac
      death. Given its important role in cardiac electrophysiology, we hypothesized
      that common genetic variation in ankyrin-B gene (ANK2) might modify QT interval
      length. METHODS AND RESULTS: The study population consisted of 1188 participants
      of the World Health Organizational Multinational Monitoring of Trends and
      Determinants in Cardiovascular Disease (WHO MONICA) general population survey
      Cooperative Health Research in the Region of Augsburg (KORA S3). Corrected QT
      interval was calculated using population specific linear regression formulas. A
      total of 22 single-nucleotide polymorphisms in the genomic region of ANK2 gene
      were genotyped using TaqMan technology. In a replication study, 6 single
      nucleotide polymorphisms were genotyped in 3890 individuals from a second
      population study (KORA S4). The rare variant of the single-nucleotide
      polymorphism rs6850768 (allele frequency, 0.28) significantly influenced duration
      of the QT interval, both in KORA S3 and KORA S4 populations. In homozygotes, the
      shortening of the QT interval was 3.79 ms (95% CI, 1.48 to 5.58; P=0.001 and
      P=0.0008 for log-additive and dominant model, respectively) in KORA S3 and 2.94
      ms (95% CI, 1.11 to 4.77; P=0.001 and P=0.006 for log-additive and dominant
      genetic model, respectively) in KORA S4. A common 2-locus haplotype (rs11098171
      rs6850768; population frequency, 28%) was associated with a QT interval
      difference of 2.85 ms (permutation; P=0.006) in KORA S3 and 1.23 ms (permutation;
      P=0.009) in KORA S4. Reverse transcription-polymerase chain reaction expression
      analysis of the human ANK2 5' genomic region in the human left ventricular tissue
      revealed 2 previously unidentified ANK2 5' exons in the proximity of the
      identified variants. CONCLUSIONS: Common genetic variants juxtaposed with novel
      exons in the distant 5' genomic region of ANK2 influence the QT interval length
      in the general population. These findings support the role of ankyrin-B in normal
      cardiac electric activity.

PMID- 20031551
TI  - Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol
      reduction and dose response.
AB  - BACKGROUND: There is interindividual variation in low-density lipoprotein
      cholesterol (LDLc) lowering by statins and limited study into the genetic
      associations of the dose dependant LDLc lowering by statins. METHODS AND RESULTS:
      Five hundred nine patients with hyperlipidemia were randomly assigned
      atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg (low-dose phase)
      followed by 80 mg, 80 mg, and 40 mg (high-dose phase), respectively. Thirty-one
      genes in statin, cholesterol, and lipoprotein metabolism were sequenced and 489
      single nucleotide polymorphisms with minor allele frequencies >2% were tested for
      associations with percentage LDLc lowering at low doses using multivariable
      adjusted general linear regression. Significant associations from the analysis at
      low dose were then repeated at high-dose statins. At low doses, only 1 single
      nucleotide polymorphism met our experiment-wide significance level, ABCA1
      rs12003906. Twenty-six subjects carried the minor allele of rs12003906, which was
      associated with an attenuated LDLc reduction (LDLc reduction in carriers versus
      noncarriers -24.1+/-2.6% versus -32.2+/-1.5%; P=0.0001). In addition, we
      replicated the association with the APOE epsilon3 allele and a reduced LDLc
      reduction. At high doses, carriers of the minor allele of ABCA1 rs12003906 and
      the APOE epsilon3 allele improved their LDLc reduction but continued to have a
      diminished LDLc reduction compared with noncarriers (-30.5+/-4.0% versus -42.0+/
      2.4%; P=0.005) and (-38.5+/-1.9% versus -45.3+/-2.8%; P=0.009), respectively.
      CONCLUSIONS: An intronic single nucleotide polymorphism in ABCA1 and the APOE
      epsilon3 allele are associated with reduced LDLc lowering by statins and identify
      individuals who may be resistant to maximal LDLc lowering by statins.

PMID- 20031552
TI  - Interactions of functional apolipoprotein E gene promoter polymorphisms with
      smoking on aortic atherosclerosis.
AB  - BACKGROUND: Apolipoprotein E gene (APOE) interacts with environmental factors in
      defining risk for atherosclerosis. We studied whether the APOE
      epsilon2/epsilon3/epsilon4 genotype or APOE promoter polymorphisms -219G/T and
      +113G/C might interact with smoking on the development of fatty streaks. We also
      studied the previously unknown effects of +113G/C on transcriptional activity.
      METHODS AND RESULTS: The fatty streak areas of aorta were measured
      morphometrically in subjects of the Helsinki Sudden Death Study. Within APOE
      epsilon3/epsilon3 subjects, there was a strong interaction between smoking and
      both -219G/T (P=0.009) and +113G/C (P=0.003) promoter polymorphisms on abdominal
      aorta fatty streak area: the -219T- and +113C-allele carriers had larger lesion
      areas compared with G/G (12.7% versus 5.9%, P=0.007; 12.9% versus 6.3%, P=0.010,
      respectively) within nonsmokers. Within smokers, the associations were inverse.
      Moreover, smoking increased the fatty streak area within -219G/G or +113G/G
      genotypes and -219G/+113G/epsilon3 haplotype carriers. Functional studies in
      reporter assay showed that in comparison with the +113G allele, the +113C allele
      had higher transcriptional activity and bound transcription factors from liver
      cell nuclear extract with significantly lower affinity. CONCLUSIONS: In middle
      aged Finnish men with APOE epsilon3/epsilon3 genotype, the APOE promoter
      polymorphisms -219G/T and +113G/C interact with smoking in modulating aortic
      atherosclerosis. The +113G/C polymorphism has an effect on transcriptional
      activity.

PMID- 20031553
TI  - Sex and age dimorphism of myocardial gene expression in nonischemic human heart
      failure.
AB  - BACKGROUND: We report the first comprehensive analysis of gene expression
      differences by sex and age in left ventricular samples from 102 patients with
      dilated cardiomyopathy. METHODS AND RESULTS: Gene expression data (HG-U133A gene
      chip, Affymetrix) were analyzed from 30 females and 72 males from 3 separate
      centers. More than 1800 genes displayed sexual dimorphism in the heart (adjusted
      P value <0.05). A significant number of these genes were highly represented in
      gene ontology pathways involved in ion transport and G-protein-coupled receptor
      signaling. Localization of these genes revealed enrichment on both the sex
      chromosomes as well as chromosomes 3, 4, and 14. The second goal of this study
      was to determine the effect of age on gene expression. Within the female cohort,
      >140 genes were differentially expressed in the <55 years age group compared with
      the >55 years age group. These genes were highly represented in gene ontology
      pathways involved in DNA damage. In contrast, zero genes in the male cohort <55
      years met statistical significance when compared with the >55 years age group.
      CONCLUSIONS: Gene expression in dilated cardiomyopathy displayed evidence of
      sexual dimorphism similar to other somatic tissues and age dimorphism within the
      female cohort.

PMID- 20031555
TI  - Progressing from risk factors to omics.

PMID- 20031554
TI  - Variants of folate metabolism genes and the risk of conotruncal cardiac defects.
AB  - BACKGROUND: Although congenital heart defects (CHD) are the most common and
      serious group of birth defects, relatively little is known about the causes of
      these conditions and there are no established prevention strategies. There is
      evidence suggesting that the risk of CHD in general, and conotruncal and
      ventricular septal defects in particular, may be related to maternal folate
      status as well as genetic variants in folate-related genes. However, efforts to
      establish the relationships between these factors and CHD risk have been hampered
      by a number of factors including small study sample sizes and phenotypic
      heterogeneity. METHODS AND RESULTS: The present study examined the relationships
      between variation in 9 folate-related genes and a subset of CHD phenotypes (ie,
      conotruncal defects, perimembranous and malalignment type ventricular septal
      defects, and isolated aortic arch anomalies) in a cohort of >700 case-parent
      triads. Further, both maternal and embryonic genetic effects were considered.
      Analyses of the study data confirmed an earlier reported association between
      embryonic genotype for MTHFR A1298C and disease risk (unadjusted P=0.002).
      CONCLUSIONS: These results represent the most comprehensive and powerful analysis
      of the relationship between CHD and folate-related genes reported to date, and
      provide additional evidence that, similar to neural tube defects, this subset of
      CHD is folate related.

PMID- 20031556
TI  - Determination of paraoxonase 1 status without the use of toxic organophosphate
      substrates.

PMID- 20031560
TI  - Contemporary approaches to gene discovery: progress toward personalized medicine?

PMID- 20031561
TI  - A gene-centric approach to elucidating cardiovascular risk.

PMID- 20031562
TI  - Prediction of cardiovascular disease outcomes and established cardiovascular risk
      factors by genome-wide association markers.
AB  - BACKGROUND: Genome-wide association (GWA) platforms have yielded a rapidly
      increasing number of new genetic markers. The ability of these markers to improve
      prediction of clinically important outcomes is debated. METHODS AND RESULTS: A
      systematic review was performed of GWA-derived markers associated with
      cardiovascular outcomes or other phenotypes that represent common established
      risk factors for cardiovascular outcomes. Sources of information included the
      National Human Genome Research Institute catalog of published GWA studies, and
      perusal of the eligible GWA articles, meta-analyses on the respective
      associations, and articles on the incremental predictive performance of common
      variants in the GWA era. A total of 95 eligible associations were retrieved from
      the National Human Genome Research Institute catalogue of published GWA studies
      as of September 2008. Of those 36 have statistical support of P<10(-7). In depth
      evaluation of the respective articles shows 28 independent associations with such
      statistical support, pertaining to coronary artery disease, myocardial
      infarction, atrial fibrillation/flutter, prolongation of QT interval, as well as
      type 2 diabetes, body mass index, high-density lipoprotein levels, low-density
      lipoprotein levels, and nicotine dependence. Between-study heterogeneity is not
      taken into account usually, but it seems common and it would pose a challenge to
      generalizability across different populations for these markers. Still limited
      data are available in non-white populations. Effect sizes are small and may be
      even smaller in subsequent replications and meta-analysis. Population
      attributable fractions are substantial, given the large frequency of the risk
      alleles. However, individualized risk measures are typically very small
      (proportion of variance explained <1% per marker). When used in conjunction with
      traditional predictors, improvement in overall prediction (eg, area under the
      curve) or risk reclassification is limited, and subject to methodological
      caveats. CONCLUSIONS: Despite very promising signals in terms of statistical
      significance, evidence for improvement in cardiovascular prediction by currently
      available markers derived from GWA studies is sparse. Clinical use of such
      markers currently would be premature.

PMID- 20031563
TI  - Genetic variants associated with myocardial infarction risk factors in over 8000
      individuals from five ethnic groups: The INTERHEART Genetics Study.
AB  - BACKGROUND: Myocardial infarction (MI) is a leading cause of death globally, but
      specific genetic variants that influence MI and MI risk factors have not been
      assessed on a global basis. METHODS AND RESULTS: We included 8795 individuals of
      European, South Asian, Arab, Iranian, and Nepalese origin from the INTERHEART
      case-control study that genotyped 1536 single-nucleotide polymorphisms (SNPs)
      from 103 genes. One hundred and two SNPs were nominally associated with MI, but
      the statistical significance did not remain after adjustment for multiple
      testing. A subset of 940 SNPs from 69 genes were tested against MI risk factors.
      One hundred and sixty-three SNPs were nominally associated with a MI risk factor
      and 13 remained significant after adjusting for multiple testing. Of these 13, 11
      were associated with apolipoprotein (Apo) B/A1 levels: 8 SNPs from 3 genes were
      associated with Apo B, and 3 cholesteryl ester transfer protein SNPs were
      associated with Apo A1. Seven of 8 of the SNPs associated with Apo B levels were
      nominally associated with MI (P<0.05), whereas none of the 3 cholesteryl ester
      transfer protein SNPs were associated with MI (P> or =0.17). Of the 3 SNPs most
      significantly associated with MI, rs7412, which defines the Apo E2 isoform, was
      associated with both a lower Apo B/A1 ratio (P=1.0x10(-7)) and lower MI risk
      (P=0.0004). Two low-density lipoprotein receptor variants, 1 intronic (rs6511720)
      and 1 in the 3' untranslated region (rs1433099) were both associated with a lower
      Apo B/A1 ratio (P<1.0x10(-5)) and a lower risk of MI (P=0.004 and P=0.003,
      respectively). CONCLUSIONS: Thirteen common SNPs were associated with MI risk
      factors. Importantly, SNPs associated with Apo B levels were associated with MI,
      whereas SNPs associated with Apo A1 levels were not. The Apo E isoform, and 2
      common low-density lipoprotein receptor variants (rs1433099 and rs6511720)
      influence MI risk in this multiethnic sample.

PMID- 20031564
TI  - Polymorphism in the CETP gene region, HDL cholesterol, and risk of future
      myocardial infarction: Genomewide analysis among 18 245 initially healthy women
      from the Women's Genome Health Study.
AB  - BACKGROUND: Recent trial data have challenged the hypothesis that cholesteryl
      ester transfer protein (CETP) and high-density lipoprotein cholesterol (HDL-C)
      have causal roles in atherothrombosis. One method to evaluate this issue is to
      examine whether polymorphisms in the CETP gene that impact on HDL-C levels also
      impact on the future development of myocardial infarction. METHODS AND RESULTS:
      In a prospective cohort of 18 245 initially healthy American women, we examined
      over 350 000 singe-nucleotide polymorphisms (SNPs) first to identify loci
      associated with HDL-C and then to evaluate whether significant SNPs within these
      loci also impact on rates of incident myocardial infarction during an average 10
      year follow-up period. Nine loci on 9 chromosomes had 1 or more SNPs associated
      with HDL-C at genome-wide statistical significance (P<5x10(-8)). However, only
      SNPs near or in the CETP gene at 16q13 were associated with both HDL-C and risk
      of incident myocardial infarction (198 events). For example, SNP rs708272 in the
      CETP gene was associated with a per-allele increase in HDL-C levels of 3.1 mg/dL
      and a concordant 24% lower risk of future myocardial infarction (age-adjusted
      hazard ratio, 0.76; 95% CI, 0.62 to 0.94), consistent with recent meta-analysis.
      Independent and again concordant effects on HDL-C and incident myocardial
      infarction were also observed at the CETP locus for rs4329913 and rs7202364.
      Adjustment for HDL-C attenuated but did not eliminate these effects. CONCLUSIONS:
      In this prospective cohort of initially healthy women, SNPs at the CETP locus
      impact on future risk of myocardial infarction, supporting a causal role for CETP
      in atherothrombosis, possibly through an HDL-C mediated pathway.

PMID- 20031565
TI  - HFE C282Y homozygosity is associated with lower total and low-density lipoprotein
      cholesterol: The hemochromatosis and iron overload screening study.
AB  - BACKGROUND: Previous studies have suggested a positive association of coronary
      heart disease risk and both serum ferritin concentrations and C282Y
      heterozygosity. Relationships between serum lipids, C282Y homozygosity, and serum
      ferritin have not been well established. METHODS AND RESULTS: The Hemochromatosis
      and Iron Overload Screening study screened 101 168 participants in primary care
      from 5 field centers in the United States and Canada with serum ferritin,
      transferrin saturation, and HFE genotyping for C282Y and H63D mutations. Serum
      lipids were measured in a subset of 176 C282Y homozygotes (63 male, 113 female
      whites) without a prior diagnosis of, family history, or treatment for
      hemochromatosis and a matched sample of participants with normal transferrin
      saturation and serum ferritin without C282Y or H63D mutations (wild-type, 123
      male, 189 female whites). The proportion of subjects who reported using
      prescription cholesterol-lowering medications was approximately 3 times higher in
      HFE wild-type subjects than C282Y homozygotes among men (22% versus 7%; P=0.02)
      and, in women, 2 times higher (16% versus 8%; P=0.07). After excluding subjects
      taking cholesterol medications, C282Y homozygotes had significantly lower mean
      total and low-density lipoprotein cholesterol concentrations than wild-type
      subjects, with larger genotypic differences for low-density lipoprotein in men (
      0.62 mmol/L; 95% CI, -0.93 to -0.33) than in women (-0.28 mmol/L; 95%, CI -0.52
      to -0.08). CONCLUSIONS: Total mean serum cholesterol and low-density lipoprotein
      levels were lower in C282Y homozygotes than in HFE wild-type participants.
      Further studies are required to determine whether this is related to iron
      overload, HFE alleles, or other factors on C282Y-positive chromosome 6p
      haplotypes.

PMID- 20031566
TI  - Association of regions on chromosomes 6 and 7 with blood pressure in Nigerian
      families.
AB  - BACKGROUND: Elevated blood pressure (BP) shares a level of heritability similar
      to many other traits related to cardiovascular risk; however, specific
      susceptibility loci have been difficult to localize. We conducted a multistage
      study of BP as a continuous trait in a low-risk West African population in which
      it was anticipated that environmental exposures would be reduced in complexity
      and intensity. In our earlier genome-wide linkage study for BP in this
      population, strong linkage evidence was noted on chromosomes 6 and 7. METHODS AND
      RESULTS: We subsequently genotyped a total of 3431 tag single-nucleotide
      polymorphisms (SNPs) in 3 regions (viz, 152.68 to 165.99 Mb on chromosome 6, 0.29
      to 20.67 Mb, and 104.09 to 123.06 Mb on chromosome 7) in 713 individuals from 199
      families. We conducted a family-based association analysis using individual SNPs
      and associated haplotypes. After correction for multiple comparisons, 6 intronic
      and 1 intergenic SNPs achieved nominal statistical significance (P<0.05) for the
      association with BP. The associated intronic SNPs include 2 in the PARK2 gene on
      chromosome 6; 2 in the KCND2 gene, and 1 each in the C7orf58 and HDAC9 genes on
      chromosome 7. The intergenic SNP is located between the RPA3 and GLCCI1 genes on
      chromosome 7. The haplotypes on which these SNPs resided were more strongly
      associated with BP than their respective single SNPs. The frequency of the "at
      risk" haplotypes ranged from 14% to 48%. CONCLUSIONS: These data provide
      preliminary evidence that regions on chromosomes 6 and 7 may influence
      susceptibility to elevations in BP.

PMID- 20031567
TI  - An evaluation of candidate genes of inflammation and thrombosis in relation to
      the risk of venous thromboembolism: The Women's Genome Health Study.
AB  - BACKGROUND: Although pathways associated with hemostasis and thrombosis are well
      documented to have an impact on venous thromboembolism (VTE), whether the
      inflammatory cascade also influences VTE risk is uncertain. METHODS AND RESULTS:
      We evaluated 51 polymorphisms from 32 inflammation-related genes (and an
      additional 19 polymorphisms from 15 thrombosis-related genes) as potential
      determinants of VTE in a prospective cohort of 22 413 white women followed over a
      10-year period. Hazard ratios (HRs) for incident VTE according to the different
      genotypes were assessed by Cox proportional-hazards models. The false discovery
      rate (FDR) was used for correction for multiple testing with a 0.20 cut point.
      During follow-up, 158 idiopathic and 180 secondary VTE events occurred. As
      anticipated, factor V Leiden (HR, 3.22; 95% CI, 1.92 to 5.40; P<0.0001;
      FDR=0.004) and the prothrombin mutation (HR, 2.57; 95% CI, 1.64 to 4.02;
      P<0.0001; FDR=0.004) were both strongly associated with incident idiopathic VTE,
      as was the rs6046 polymorphism in the factor VII gene (HR, 0.54; 95% CI, 0.35 to
      0.86; P=0.008; FDR, 0.12). With regard to polymorphism in the inflammatory genes,
      variation at rs1143634 in the IL-1beta gene was associated with a reduced risk of
      idiopathic VTE (HR, 0.59; 95% CI, 0.44 to 0.80; P=0.0007; FDR=0.02), whereas
      variation at rs1800872 in the IL-10 gene was associated with increased risk (HR,
      1.42; 95% CI, 1.12 to 1.80; P=0.004; FDR=0.07). By contrast, no significant
      associations were found for secondary VTE events. CONCLUSIONS: In addition to
      previously reported polymorphisms associated with hemostasis and thrombosis,
      these prospective cohort data suggest that genetic variation in IL-1 beta and IL
      10 genes may also influence the risk of idiopathic VTE.

PMID- 20031569
TI  - How should hypertrophic cardiomyopathy be classified?: What's in a name? Dilemmas
      in nomenclature characterizing hypertrophic cardiomyopathy and left ventricular
      hypertrophy.

PMID- 20031568
TI  - Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium:
      Design of prospective meta-analyses of genome-wide association studies from 5
      cohorts.
AB  - BACKGROUND: The primary aim of genome-wide association studies is to identify
      novel genetic loci associated with interindividual variation in the levels of
      risk factors, the degree of subclinical disease, or the risk of clinical disease.
      The requirement for large sample sizes and the importance of replication have
      served as powerful incentives for scientific collaboration. Methods- The Cohorts
      for Heart and Aging Research in Genomic Epidemiology Consortium was formed to
      facilitate genome-wide association studies meta-analyses and replication
      opportunities among multiple large population-based cohort studies, which collect
      data in a standardized fashion and represent the preferred method for estimating
      disease incidence. The design of the Cohorts for Heart and Aging Research in
      Genomic Epidemiology Consortium includes 5 prospective cohort studies from the
      United States and Europe: the Age, Gene/Environment Susceptibility-Reykjavik
      Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health
      Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data
      on a total of about 38 000 individuals, these cohort studies have a large number
      of health-related phenotypes measured in similar ways. For each harmonized trait,
      within-cohort genome-wide association study analyses are combined by meta
      analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly
      selected level of genome-wide statistical significance, is a powerful approach to
      finding genuine phenotypic associations with novel genetic loci. CONCLUSIONS: The
      Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and
      collaborating non-member studies or consortia provide an excellent framework for
      the identification of the genetic determinants of risk factors, subclinical
      disease measures, and clinical events.

PMID- 20031570
TI  - How should hypertrophic cardiomyopathy be classified?: Molecular diagnosis for
      hypertrophic cardiomyopathy: Not ready for prime time.

PMID- 20031572
TI  - Defining the pathogenicity of DNA sequence variation.

PMID- 20031573
TI  - Sex-specific familial clustering of myocardial infarction in patients with acute
      coronary syndromes.
AB  - BACKGROUND: Family history of premature myocardial infarction (MI) in first
      degree relatives is a risk factor for MI and an indication for primary
      prevention. Although excess mother-to-daughter "transmission" occurs in ischemic
      stroke, no published studies have considered sex-of-parent/sex-of-proband
      interactions in the heritability of MI. METHODS AND RESULTS: In a population
      based study (Oxford Vascular Study) of all patients with acute coronary syndromes
      (ACS), irrespective of age, family history of all acute vascular events and
      related risk factors were analyzed by sex and age of both probands and first
      degree relatives. Premature events were categorized as occurring at age <65
      years. Of 835 probands with 1 or more ACS, 623 (420 men) had incident events and
      complete family history data. In probands with premature ACS, maternal history of
      both MI and of all vascular events were more common in female than male probands
      (odds ratio [OR], 2.25; 95% CI, 1.02 to 4.94; P=0.04 and OR, 3.03; 95% CI, 1.47
      to 6.26; P=0.002, respectively). No such effect existed for paternal history (OR,
      1.00; 95% CI, 0.46 to 2.10; P=0.99 and OR, 1.19; 95% CI, 0.58 to 2.43; P=0.63,
      respectively). Age at ACS in probands was highly correlated with age at MI in
      mothers (r=0.46, P<0.001), regardless of the proband's sex. Consequently, history
      of premature maternal MI was strongly associated with premature ACS and premature
      MI in female (OR, 10.52; 95% CI, 2.17 to 56.6; P=0.001 and OR, 7.31; 95% CI, 1.55
      to 34.6; P=0.004, respectively) and male probands (OR, 3.88; 95% CI, 1.20 to
      12.6; P=0.01 and OR, 3.63; 95% CI, 1.13 to 11.60; P=0.02, respectively).
      CONCLUSIONS: Important sex-of-parent/sex-of-proband interactions exist in the
      family history of MI in patients with ACS. Greater emphasis should be placed on
      maternal than paternal history of MI, particularly in women aged <65 years.

PMID- 20031574
TI  - Genome-wide identification of allelic expression in hypertensive rats.
AB  - BACKGROUND: Identification of genes involved in complex cardiovascular disease
      traits has proven challenging. Inbred animal models can facilitate genetic
      studies of disease traits. The spontaneously hypertensive rat (SHR) is an inbred
      model of hypertension that exists in several closely related but genetically
      distinct lines. METHODS AND RESULTS: We used renal gene-expression profiling
      across 3 distinct SHR lines to identify genes that show different expression in
      SHR than in the genetically related normotensive control strain, Wistar-Kyoto. To
      ensure robust discovery of genes showing SHR-specific expression differences, we
      considered only those genes in which differential expression is replicated in
      multiple animals of each of multiple hypertensive rat lines at multiple time
      points during the ontogeny of hypertension. Mutation analysis was performed on
      the identified genes to uncover allelic variation. We identified those genes in
      which all SHR lines share a single allele of the gene when normotensive controls
      (Wistar-Kyoto) have fixed the alternative allele. We then identified which of the
      differentially expressed genes show expression that is controlled by the alleleic
      variation present in and around the gene. Allelic expression was demonstrated by
      observing the effect on gene expression of alleles inherited in the freely
      segregating F(2) progeny of a cross between SHR and Wistar-Kyoto animals.
      CONCLUSIONS: The result of these studies is the identification of several genes
      (Ptprj, Ela1, Dapk-2, and Gstt2) in which each of 4 SHR lines examined have fixed
      the same allele and in which each of 2 Wistar-Kyoto lines have a contrasting
      allele for which the inherited allele influences the level of gene expression. We
      further show that alleles of these genes lie in extensive haplotype blocks that
      have been inherited identical by descent in the hypertensive lines.

PMID- 20031575
TI  - Time-warped comparison of gene expression in adaptive and maladaptive cardiac
      hypertrophy.
AB  - BACKGROUND: Cardiac hypertrophy is classically regarded as a compensatory
      response, yet the active tissue remodeling processes triggered by various types
      of mechanical stress can enhance or diminish the function of the heart. Despite
      the disparity in outcomes, there are similarities in the hypertrophic responses.
      We hypothesized that a generic genetic response that is not dependent on the
      particular nature of the hypertrophic stimulus exists. To test our hypothesis, we
      compared the temporal evolution of transcriptomes measured in hearts subjected to
      either adaptive (exercise-induced) or maladaptive (aortic banding-induced)
      hypertrophy. METHODS AND RESULTS: Generic hypertrophy-associated genes were
      identified and distinguished from stimulus-dependent transcripts by coupling a
      metric of cardiac growth with a dynamic time-warping algorithm to align
      transcriptome changes with respect to the hypertrophy response. The major
      differences in expression between the adaptive and maladaptive hypertrophy models
      were centered around the genes involved in metabolism, fibrosis, and immune
      response. Conversely, transcripts with common expression patterns in both
      hypertrophy models were associated with signal transduction, cytoskeletal
      development, and muscle contraction. Thus, despite the apparent differences in
      the expression response of the heart to either athletic conditioning or pressure
      overload, there is a set of genes that displays similar expression profiles.
      CONCLUSIONS: This finding lends support to the notion of a generalized cardiac
      growth mechanism that is activated in response to mechanical perturbation. The
      common and unique genetic signatures of adaptive and maladaptive hypertrophy may
      be useful in the diagnosis and treatment of pathological myocardial remodeling.

PMID- 20031577
TI  - Novel loci, including those related to Crohn disease, psoriasis, and
      inflammation, identified in a genome-wide association study of fibrinogen in 17
      686 women: the Women's Genome Health Study.
AB  - BACKGROUND: Fibrinogen is a multifunctional circulating glycoprotein involved in
      wound healing, thrombosis, platelet aggregation, and inflammation, and elevated
      levels predict vascular disease. Despite evidence of crucial biological function
      and moderate heritability, comprehensive analysis of the influence of genetic
      variation on fibrinogen is not available. METHODS AND RESULTS: To address this
      issue, we undertook a genome-wide association study evaluating the potential
      relationships between 337 343 single-nucleotide polymorphisms (SNPs) and plasma
      fibrinogen levels among 17 686 apparently healthy women participating in the
      Women's Genome Health Study. As C-reactive protein is also an inflammatory marker
      known to predict cardiovascular diseases, we compared the determinants of
      fibrinogen levels with those of C-reactive protein. Four novel loci were
      identified, in addition to the fibrinogen gene cluster, which were associated
      with fibrinogen levels at genome-wide levels of significance (range of
      probability values from 8.82 x 10(-09) to 8.04 x 10(-39)). Two of the loci are
      related to common chronic inflammatory diseases: the first, at locus 5q31.1
      (SLC22A5, SLC22A4, IRF1), lies immediately adjacent to a locus linked to Crohn
      disease (P value for lead SNP, 1.24 x 10(-12)) and the second, at locus 17q25.1
      (CD300LF, SLC9A3R1, NAT9), has been associated with psoriasis (P value for lead
      SNP, 7.72 x 10(-11)). A third locus at 1q21.3 (IL6R) lies within the interleukin
      6 receptor gene, a critical component of the inflammatory cascade (P value for
      lead SNP, 1.80 x 10(-11)). A novel locus at 2q34 (CPSI) participates in the urea
      cycle (P=8.82 x 10(-09)). The majority of implicated SNPs showed little evidence
      of dual association with C-reactive protein levels. CONCLUSIONS: A genome-wide
      survey of the human genome identifies novel loci related to common chronic
      inflammatory diseases as genetic determinants of fibrinogen levels, in addition
      to loci that relate to the inflammatory cascade, the urea cycle, and the
      fibrinogen gene cluster.

PMID- 20031578
TI  - Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a
      healthy population: a genome-wide evaluation of 13 974 participants in the
      Women's Genome Health Study.
AB  - BACKGROUND: Homocysteine is a sulfur amino acid whose plasma concentration has
      been associated with the risk of cardiovascular diseases, neural tube defects,
      and loss of cognitive function in epidemiological studies. Although genetic
      variants of MTHFR and CBS are known to influence homocysteine concentration,
      common genetic determinants of homocysteine remain largely unknown. METHODS AND
      RESULTS: To address this issue comprehensively, we performed a genome-wide
      association analysis, testing 336 469 single-nucleotide polymorphisms in 13 974
      healthy white women. Although we confirm association with MTHFR (1p36.22;
      rs1801133; P=8.1 x 10(-35)) and CBS (21q22.3; rs6586282; P=3.2 x 10(-10)), we
      found novel associations with CPS1 (2q34; rs7422339; P=1.9 x 10(-11)), MUT
      (6p12.3; rs4267943; P=2.0 x 10(-9)), NOX4 (11q14.3; rs11018628; P=9.6 x 10(-12)),
      and DPEP1 (16q24.3; rs1126464; P=1.2 x 10(-12)). The associations at MTHFR,
      DPEP1, and CBS were replicated in an independent sample from the PROCARDIS study,
      whereas the association at CPS1 was only replicated among the women. CONCLUSIONS:
      These associations offer new insight into the biochemical pathways involved in
      homocysteine metabolism and provide opportunities to better delineate the role of
      homocysteine in health and disease.

PMID- 20031580
TI  - Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a
      large-scale genetic association study.
AB  - BACKGROUND: Epidemiological studies indicate a genetic contribution to ischemic
      stroke risk, but specific genetic variants remain unknown, with the exception of
      a few rare variants. Recent genome-wide association studies identified and
      replicated common genetic variants on chromosome 9p21 to confer risk of coronary
      heart disease. We examined whether these variants are associated with ischemic
      stroke. METHODS AND RESULTS: We genotyped 6 common genetic variants on chromosome
      9p21, previously associated with coronary artery disease in genome-wide
      association studies, in 2 population-based studies in southern Sweden, the Lund
      Stroke Register (n=1837 cases, 947 controls) and the Malmo Diet and Cancer study
      (MDC; n=888 cases, 893 controls). We examined association in each study and in
      the pooled dataset. Adjustments were made for cardiovascular risk factors and
      further for previous myocardial infarction in MDC. We found a modest increase in
      ischemic stroke risk for 2 common (minor allele frequencies 0.46 to 0.49)
      variants, rs2383207 (P=0.04 in Lund Stroke Register, P=0.01 in MDC) and
      rs10757274 (P=0.03 in Lund Stroke Register, P=0.03 in MDC), in each sample
      independently. The strength of the association increased when samples were pooled
      with an odds ratio of 1.15 (95% CI, 1.05 to 1.25; P=0.002) for the strongest
      variant rs2383207. Results were similar after adjustment for clinical covariates.
      rs1333049 also showed significant association in MDC, which increased in the
      pooled sample (P=0.004). CONCLUSIONS: In this large sample (n=4565), we detected
      common genetic determinants for ischemic stroke on chromosome 9p21. Our findings
      indicate that ischemic stroke shares pathophysiological determinants with
      coronary heart disease and other arterial diseases and highlight the need for
      large sample sizes in stroke genetics.

PMID- 20031579
TI  - COL4A1 is associated with arterial stiffness by genome-wide association scan.
AB  - BACKGROUND: Pulse wave velocity (PWV), a noninvasive index of central arterial
      stiffness, is a potent predictor of cardiovascular mortality and morbidity.
      Heritability and linkage studies have pointed toward a genetic component
      affecting PWV. We conducted a genome-wide association study to identify single
      nucleotide polymorphisms (SNPs) associated with PWV. METHODS AND RESULTS: The
      study cohort included participants from the SardiNIA study for whom PWV measures
      were available. Genotyping was performed in 4221 individuals, using either the
      Affymetrix 500K or the Affymetrix 10K mapping array sets (with imputation of the
      missing genotypes). Associations with PWV were evaluated using an additive
      genetic model that included age, age(2), and sex as covariates. The findings were
      tested for replication in an independent internal Sardinian cohort of 1828
      individuals, using a custom chip designed to include the top 43 nonredundant SNPs
      associated with PWV. Of the loci that were tested for association with PWV, the
      nonsynonymous SNP rs3742207 in the COL4A1 gene on chromosome 13 and SNP rs1495448
      in the MAGI1 gene on chromosome 3 were successfully replicated (P=7.08 x 10(-7)
      and P=1.06 x 10(-5), respectively, for the combined analyses). The association
      between rs3742207 and PWV was also successfully replicated (P=0.02) in an
      independent population, the Old-Order Amish, leading to an overall P=5.16 x 10(
      8). CONCLUSIONS: A genome-wide association study identified a SNP in the COL4A1
      gene that was significantly associated with PWV in 2 populations. Collagen type 4
      is the major structural component of basement membranes, suggesting that
      previously unrecognized cell-matrix interactions may exert an important role in
      regulating arterial stiffness.

PMID- 20031581
TI  - Association and functional analyses of MEF2A as a susceptibility gene for
      premature myocardial infarction and coronary artery disease.
AB  - BACKGROUND: Mutations in the MEF2A gene, coding for a member of the myocyte
      enhancer factor 2 family of transcription factors, have been reported in patients
      with coronary artery disease and myocardial infarction (MI). In particular, a 21
      bp deletion and 3 missense mutations were demonstrated either to reduce MEF2A
      transcriptional activity or to impair its nuclear translocation. However, the
      association of MEF2A with coronary artery disease/MI was not confirmed in other
      studies. We analyzed the role of MEF2A in the pathogenesis of MI in 2008 Italian
      patients with premature MI and in 2008 controls. METHODS AND RESULTS: Mutational
      screening of exon 8 (containing all so-far reported point mutations) disclosed 5
      novel and 2 previously described missense mutations. Microsatellite genotyping
      and sequencing revealed the presence of the 21-bp deletion (located in exon 12)
      in 5 cases and in none of the controls. Functional studies on mutant proteins
      showed no alteration, neither in the transactivating properties (all mutants) nor
      in the nuclear localization (21-bp deletion). Furthermore, an association
      analysis performed using 3 microsatellites at the MEF2A locus showed no
      significant association with MI. These results were confirmed in a replication
      study performed on an independent Italian population with coronary artery
      disease. CONCLUSIONS: All together, our data do not support MEF2A as a
      susceptibility gene for coronary artery disease/MI in the Italian population.

PMID- 20031582
TI  - Comprehensive whole-genome and candidate gene analysis for response to statin
      therapy in the Treating to New Targets (TNT) cohort.
AB  - BACKGROUND: Statins are effective at lowering low-density lipoprotein cholesterol
      and reducing risk of cardiovascular disease, but variability in response is not
      well understood. To address this, 5745 individuals from the Treating to New
      Targets (TNT) trial were genotyped in a combination of a whole-genome and
      candidate gene approach to identify associations with response to atorvastatin
      treatment. METHODS AND RESULTS: A total of 291 988 single-nucleotide
      polymorphisms (SNPs) from 1984 individuals were analyzed for association with
      statin response, followed by genotyping top hits in 3761 additional individuals.
      None was significant at the whole-genome level in either the initial or follow-up
      test sets for association with low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, or triglyceride response. In addition to the whole
      genome platform, 23 candidate genes previously associated with statin response
      were analyzed in these 5745 individuals. Three SNPs in apoE were most highly
      associated with low-density lipoprotein cholesterol response, followed by 1 in
      PCSK9 with a similar effect size. At the candidate gene level, SNPs in HMGCR were
      also significant though the effect was less than with those in apoE and PCSK9.
      rs7412/apoE had the most significant association (P=6x10(-30)), and its high
      significance in the whole-genome study (P=4x10(-9)) confirmed the suitability of
      this population for detecting effects. Age and gender were found to influence low
      density lipoprotein cholesterol response to a similar extent as the most
      pronounced genetic effects. CONCLUSIONS: Among SNPs tested with an allele
      frequency of at least 5%, only SNPs in apoE are found to influence statin
      response significantly. Less frequent variants in PCSK9 and smaller effect sizes
      in SNPs in HMGCR were also revealed.

PMID- 20031576
TI  - Association of novel genetic Loci with circulating fibrinogen levels: a genome
      wide association study in 6 population-based cohorts.
AB  - BACKGROUND: Fibrinogen is both central to blood coagulation and an acute-phase
      reactant. We aimed to identify common variants influencing circulation fibrinogen
      levels. METHODS AND RESULTS: We conducted a genome-wide association analysis on 6
      population-based studies, the Rotterdam Study, the Framingham Heart Study, the
      Cardiovascular Health Study, the Atherosclerosis Risk in Communities Study, the
      Monitoring of Trends and Determinants in Cardiovascular Disease/KORA Augsburg
      Study, and the British 1958 Birth Cohort Study, including 22 096 participants of
      European ancestry. Four loci were marked by 1 or more single-nucleotide
      polymorphisms that demonstrated genome-wide significance (P<5.0 x 10(-8)). These
      included a single-nucleotide polymorphism located in the fibrinogen beta chain
      (FGB) gene and 3 single-nucleotide polymorphisms representing newly identified
      loci. The high-signal single-nucleotide polymorphisms were rs1800789 in exon 7 of
      FGB (P=1.8 x 10(-30)), rs2522056 downstream from the interferon regulatory factor
      1 (IRF1) gene (P=1.3 x 10(-15)), rs511154 within intron 1 of the propionyl
      coenzyme A carboxylase (PCCB) gene (P=5.9 x 10(-10)), and rs1539019 on the NLR
      family pyrin domain containing 3 isoforms (NLRP3) gene (P=1.04 x 10(-8)).
      CONCLUSIONS: Our findings highlight biological pathways that may be important in
      regulation of inflammation underlying cardiovascular disease.

PMID- 20031583
TI  - Multiple mutations in genetic cardiovascular disease: a marker of disease
      severity?

PMID- 20031585
TI  - Analysis of complex disease association and linkage studies using the University
      of California Santa Cruz Genome Browser.

PMID- 20031584
TI  - Genetics of atherothrombotic and lacunar stroke.

PMID- 20031587
TI  - Letter by Sullivan regarding article, "HFE C282Y homozygosity is associated with
      lower total and low-density lipoprotein cholesterol: the hemochromatosis and iron
      overload screening study".

PMID- 20031588
TI  - The report card on growth differentiation factor 15: consistent marks but not yet
      ready for promotion.

PMID- 20031589
TI  - Evidence for coregulation of myocardial gene expression by MEF2 and NFAT in human
      heart failure.
AB  - BACKGROUND: Pathological stresses induce heart failure in animal models through
      activation of multiple cardiac transcription factors (TFs) working cooperatively.
      However, interactions among TFs in human heart failure are less understood. Here,
      we use genomic data to examine the evidence that 5 candidate TF families
      coregulate gene expression in human heart failure. METHODS AND RESULTS: RNA
      isolates from failing (n=86) and nonfailing (n=16) human hearts were hybridized
      with Affymetrix HU133A arrays. For each gene on the array, we determined
      conserved MEF2, NFAT, NKX , GATA , and FOX binding motifs within the -1-kb
      promoter region using human-murine sequence alignments and the TRANSFAC database.
      Across 9076 genes expressed in the heart, TF-binding motifs tended to cluster
      together in nonrandom patterns within promoters of specific genes (P values
      ranging from 10(-2) to 10(-21)), suggesting coregulation. We then modeled
      differential expression as a function of TF combinations present in promoter
      regions. Several combinations predicted increased odds of differential expression
      in the failing heart, with the highest odds ratios noted for genes containing
      both MEF2 and NFAT binding motifs together in the same promoter region (peak odds
      ratio, 3.47; P=0.005). CONCLUSIONS: These findings provide genomic evidence for
      coregulation of myocardial gene expression by MEF2 and NFAT in human heart
      failure. In doing so, they extend the paradigm of combinatorial regulation of
      gene expression to the human heart and identify new target genes for mechanistic
      study. More broadly, we demonstrate how integrating diverse sources of genomic
      data yields novel insight into human cardiovascular disorders.

PMID- 20031590
TI  - The relation of genetic and environmental factors to systemic inflammatory
      biomarker concentrations.
AB  - BACKGROUND: Environmental and genetic correlates of inflammatory marker
      variability are incompletely understood. In the family-based Framingham Heart
      Study, we investigated heritability and candidate gene associations of systemic
      inflammatory biomarkers. METHODS AND RESULTS: In offspring participants (n=3710),
      we examined 11 inflammatory biomarkers (CD40 ligand, C-reactive protein,
      intercellular adhesion molecule-1, interleukin-6, urinary isoprostanes, monocyte
      chemoattractant protein-1, myeloperoxidase, P-selectin, tumor necrosis factor
      alpha, tumor necrosis factor receptor II, fibrinogen). Heritability and bivariate
      genetic and environmental correlations were assessed by Sequential Oligogenic
      Linkage Analysis routines in 1012 family members. We examined 1943 tagging single
      nucleotide polymorphisms in 233 inflammatory pathway genes with >or=5 minor
      allele carriers using a general genetic linear model. Clinical correlates
      explained 2.4% (CD40 ligand) to 28.5% (C-reactive protein) of the variability in
      inflammatory biomarkers. Estimated heritability ranged from 10.9% (isoprostanes)
      to 44.8% (P-selectin). Most correlations between biomarkers were weak although
      statistically significant. A total of 45 single-nucleotide polymorphism-biomarker
      associations met the q-value threshold of 0.25. Novel top single-nucleotide
      polymorphisms were observed in ICAM1 gene in relation to intercellular adhesion
      molecule-1 concentrations (rs1799969, P=1.32 x 10(-8)) and MPO in relation to
      myeloperoxidase (rs28730837, P=1.9 x 10(-5)). Lowest P values for trans-acting
      single-nucleotide polymorphisms were observed for APCS with monocyte
      chemoattractant protein-1 concentrations (rs1374486, P=1.01 x 10(-7)) and
      confirmed for IL6R with interleukin-6 concentrations (rs8192284, P=3.36 x 10(
      5)). Novel potential candidates (APCS, MPO) need to be replicated. CONCLUSIONS:
      Our community-based data support the relevance of clinical and genetic factors
      for explaining variation in inflammatory biomarker traits.

PMID- 20031591
TI  - Association of blood lipids with common DNA sequence variants at 19 genetic loci
      in the multiethnic United States National Health and Nutrition Examination Survey
      III.
AB  - BACKGROUND: Using the genome-wide association approach in individuals of European
      ancestry, we and others recently identified single-nucleotide polymorphisms
      (SNPs) at 19 loci as associated with blood lipids; 8 of these loci were novel.
      Whether these same SNPs associate with lipids in a broader range of ethnicities
      is unknown. METHODS AND RESULTS: We genotyped index SNPs at 19 loci in the Third
      United States National Health and Nutrition Examination Survey (n=7159), a
      population-based probability sample of the United States comprised primarily of
      non-Hispanic blacks, Mexican Americans, and non-Hispanic whites. We constructed
      ethnic-specific residual blood lipid levels after adjusting for age and gender.
      Ethnic-specific linear regression was used to test the association of genotype
      with blood lipids. To summarize the statistical evidence across 3 racial groups,
      we conducted a fixed-effects variance-weighted meta-analysis. After exclusions,
      there were 1627 non-Hispanic blacks, 1659 Mexican Americans, and 2230 non
      Hispanic whites. At 5 loci (1p13 near CELSR2/PSRC1/SORT1, HMGCR, CETP, LPL, and
      APOA5), the index SNP was associated with low-density lipoprotein cholesterol,
      high-density lipoprotein cholesterol, or triglycerides in all 3 ethnic groups. At
      the remaining loci, there was mixed evidence by ethnic group. In meta-analysis,
      we found that, at 14 of the 19 loci, SNPs exceeded a nominal P<0.05. CONCLUSIONS:
      At 5 loci including the recently discovered region on 1p13 near
      CELSR2/PSRC1/SORT1, the same SNP discovered in whites associates with blood
      lipids in non-Hispanic blacks and Mexican Americans. For the remaining loci, fine
      mapping and resequencing will be required to definitively evaluate the relevance
      of each locus in individuals of African and Hispanic ancestries.

PMID- 20031593
TI  - The FTO gene is associated with an atherogenic lipid profile and myocardial
      infarction in patients with type 2 diabetes: a Genetics of Diabetes Audit and
      Research Study in Tayside Scotland (Go-DARTS) study.
AB  - BACKGROUND: Common variation in the fat mass and obesity (FTO)-related gene is
      associated with increased body fat and susceptibility to type 2 diabetes. We
      hypothesized that this would also associate with metabolic phenotypes of insulin
      resistance and increased risk of cardiovascular morbidity and mortality. METHODS
      AND RESULTS: FTO rs9939609 genotype was determined in 4897 patients with type 2
      diabetes in the prospective Genetics of Diabetes Audit and Research Study in
      Tayside Scotland study. The A allele was associated with lower plasma high
      density lipoprotein cholesterol (mean difference, 0.03 mmol/L; P=0.008), higher
      triglycerides (0.1 mmol/L, P=0.007), higher atherogenic index of plasma (0.03,
      P=0.003), and, as expected, increased body mass index (0.77 kg/m(2), P=8.8 x 10(
      6)). During a mean follow-up of 3.6 years, the A allele was also associated with
      increased risk (hazard ratio, 2.36; CI, 1.49 to 3.74; P=0.0002) of fatal and
      nonfatal myocardial infarction (total of 324 events) in a model, including
      baseline age, gender, prevalent myocardial infarction, smoking status, statin,
      and insulin use. This association diminished but remained significant when
      obesity-related traits, such as body mass index, glycohemoglobin, and lipid
      parameters, were also included (hazard ratio, 2.01; CI, 1.18 to 3.45, P=0.011).
      There was a strong interaction of FTO genotype and statin use and cardiovascular
      outcome (P=0.001), such that cardiovascular morbidity and mortality was
      completely abrogated in individuals who were prescribed statins. CONCLUSIONS: The
      increased fat mass in carriers of the A allele of rs9939609 of FTO is associated
      not only with increased risk of type 2 diabetes, but also with an increase in
      atherogenic lipid profile and myocardial infarction in these patients. This
      variant may, therefore, in the future contribute to more effective targeting of
      specific preventative therapy.

PMID- 20031592
TI  - Common coding variants of the HNF1A gene are associated with multiple
      cardiovascular risk phenotypes in community-based samples of younger and older
      European-American adults: the Coronary Artery Risk Development in Young Adults
      Study and The Cardiovascular Health Study.
AB  - BACKGROUND: The transcription factor hepatocyte nuclear factor (HNF)-1 alpha
      regulates the activity of a number of genes involved in innate immunity, blood
      coagulation, lipid and glucose transport and metabolism, and cellular
      detoxification. Common polymorphisms of the HNF-1 alpha gene (HNF1A) were
      recently associated with plasma C-reactive protein and gamma-glutamyl transferase
      concentration in middle-aged to older European Americans (EA). METHODS AND
      RESULTS: We assessed whether common variants of HNF1A are associated with C
      reactive protein, gamma-glutamyl transferase, and other atherosclerotic and
      metabolic risk factors, in the large, population-based Coronary Artery Risk
      Development in Young Adults Study of healthy young EA (n=2154) and African
      American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and
      Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units
      lower C-reactive protein and gamma-glutamyl transferase levels in EA. The same
      HNF1A coding variants were associated with higher low-density lipoprotein
      cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated
      the associations between HNF1A coding variants and C-reactive protein,
      fibrinogen, low-density lipoprotein cholesterol, and renal function in a second
      population-based sample of EA adults 65 years and older from the Cardiovascular
      Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated
      with increased risk of subclinical coronary atherosclerosis in Coronary Artery
      Risk Development in Young Adults and with incident coronary heart disease in
      Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less
      common in AA than in EA. There was little evidence of association between HNF1A
      genotype and atherosclerosis-related phenotypes in AA. CONCLUSIONS: Common
      polymorphisms of HNF1A seem to influence multiple phenotypes related to
      cardiovascular risk in the general population of younger and older EA adults.

PMID- 20031594
TI  - A common variant of the FTO gene is associated with not only increased adiposity
      but also elevated blood pressure in French Canadians.
AB  - BACKGROUND: FTO is the first gene established as contributing to common forms of
      obesity. The gene is highly expressed in the hypothalamus and is thought to
      mediate this effect through its influence on energy homeostasis. The
      hypothalamus, however, also regulates blood pressure (BP). Therefore, we
      investigated whether the FTO-risk variant is associated not only with increased
      adiposity but also with elevated BP and whether the latter may be mediated, in
      part, by increased sympathetic modulation of vasomotor tone. METHODS AND RESULTS:
      The primary study was carried out in 485 adolescents recruited from a French
      Canadian founder population who underwent detailed body-composition and
      cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and
      anthropometry. BP was recorded beat to beat at rest and during physical and
      mental challenges. Sympathetic modulation of vasomotor tone was assessed with
      power spectral analysis of BP. We found that individuals with the FTO-risk
      genotype compared with those without it demonstrate greater adiposity, including
      the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP
      throughout the entire protocol, with a maximum difference during a mental stress
      (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index
      of sympathetic modulation of vasomotor tone. A replication in an independent
      sample of adults from the same founder population confirmed the association
      between FTO and BP. CONCLUSIONS: These results suggest that, in a French Canadian
      founder population, FTO may increase not only risk for obesity, as demonstrated
      in other populations, but also for hypertension. The latter may be related, at
      least in part, to the regulation of sympathetic vasomotor tone.

PMID- 20031595
TI  - A mutation in the beta 3 subunit of the cardiac sodium channel associated with
      Brugada ECG phenotype.
AB  - BACKGROUND: Brugada syndrome, characterized by ST-segment elevation in the right
      precordial ECG leads and the development of life-threatening ventricular
      arrhythmias, has been associated with mutations in 6 different genes. We identify
      and characterize a mutation in a new gene. METHODS AND RESULTS: A 64-year-old
      white male displayed a type 1 ST-segment elevation in V1 and V2 during
      procainamide challenge. Polymerase chain reaction-based direct sequencing was
      performed using a candidate gene approach. A missense mutation (L10P) was
      detected in exon 1 of SCN3B, the beta 3 subunit of the cardiac sodium channel,
      but not in any other gene known to be associated with Brugada syndrome or in 296
      controls. Wild-type (WT) and mutant genes were expressed in TSA201 cells and
      studied using whole-cell patch-clamp techniques. Coexpression of
      SCN5A/WT+SCN1B/WT+SCN3B/L10P resulted in an 82.6% decrease in peak sodium current
      density, accelerated inactivation, slowed reactivation, and a -9.6-mV shift of
      half-inactivation voltage compared with SCN5A/WT+SCN1B/WT+SCN3B/WT. Confocal
      microscopy revealed that SCN5A/WT channels tagged with green fluorescent protein
      are localized to the cell surface when coexpressed with WT SCN1B and SCN3B but
      remain trapped in intracellular organelles when coexpressed with SCN1B/WT and
      SCN3B/L10P. Western blot analysis confirmed the presence of Na(V)beta 3 in human
      ventricular myocardium. CONCLUSIONS: Our results provide support for the
      hypothesis that mutations in SCN3B can lead to loss of transport and functional
      expression of the hNa(v)1.5 protein, leading to reduction in sodium channel
      current and clinical manifestation of a Brugada phenotype.

PMID- 20031597
TI  - Growth-differentiation factor-15 for risk stratification in patients with stable
      and unstable coronary heart disease: results from the AtheroGene study.
AB  - BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a stress-responsive
      transforming growth factor-beta-related cytokine that has emerged as a prognostic
      biomarker in acute coronary syndrome trial populations. Its predictive role in
      stable coronary heart disease (CHD) has never been assessed. METHODS AND RESULTS:
      The circulating levels of GDF-15 were measured by immunoradiometric assay in
      patients with stable angina pectoris (n=1352) or acute coronary syndrome (n=877)
      who were followed up for a median of 3.6 years. Stable angina pectoris patients
      presenting with normal (<1200 ng/L), moderately elevated (1200 to 1800 ng/L), or
      markedly elevated (>1800 ng/L) GDF-15 levels had 3.6-year CHD mortality rates of
      1.4%, 2.7%, and 15.0%, respectively (P<0.001). By backward stepwise Cox
      regression analysis, which adjusted for age and gender, clinical variables, the
      number of diseased vessels, renal function, the levels of C-reactive protein,
      cardiac troponin I, and N-terminal pro-B-type natriuretic peptide, GDF-15
      remained an independent predictor of CHD mortality (P<0.001). Addition of GDF-15
      improved the prognostic accuracy of a clinical risk prediction model concerning
      CHD mortality (c-statistic, 0.84 versus 0.74; P=0.005). Analysis of the acute
      coronary syndrome part of the study population confirmed GDF-15 as an independent
      predictor of CHD mortality (P<0.001). The circulating levels of GDF-15 did not
      predict the future risk of nonfatal myocardial infarction in patients with stable
      angina pectoris or acute coronary syndrome. CONCLUSIONS: This study identifies
      GDF-15 as a strong and independent predictor of CHD mortality across the broad
      spectrum of patients with stable and unstable CHD.

PMID- 20031596
TI  - Impact of adding a single allele in the 9p21 locus to traditional risk factors on
      reclassification of coronary heart disease risk and implications for lipid
      modifying therapy in the Atherosclerosis Risk in Communities study.
AB  - BACKGROUND: A single-nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21
      allele), has been shown to predict coronary heart disease (CHD) in whites. We
      evaluated whether adding the 9p21 allele to traditional risk factors (RFs)
      improved CHD risk prediction in whites from the Atherosclerosis Risk in
      Communities study and whether changes in risk prediction would modify lipid
      therapy recommendations. METHODS AND RESULTS: Whites (n=9998) in the
      Atherosclerosis Risk in Communities study for whom the 9p21 genotype and
      traditional RF information was available were included. Using Cox proportional
      hazards models, the Atherosclerosis Risk in Communities Cardiovascular Risk
      Score, which is based on traditional RFs, was determined. A total of 1349
      individuals (13.5%) developed incident CHD events during a period of 14.6 years.
      Adding the 9p21 allele to traditional RFs was associated with a hazard ratio of
      incident CHD of 1.2 per allele (P<0.000003) and a significant increase in the
      area under the curve of the receiver operating characteristic from 0.782 to 0.786
      (95% CI, 0.001, 0.007). The 9p21 allele's greatest influence to the
      Atherosclerosis Risk in Communities Cardiovascular Risk Score was observed in the
      intermediate-low (>5% to <or=10% 10-year CHD risk) and intermediate-high (>10% to
      <or=20% 10-year CHD risk) categories, with 12.1% and 12.6% reclassified,
      respectively. This may impact therapy because 90% of these reclassified
      individuals had low-density lipoprotein cholesterol >100 mg/dL. CONCLUSIONS:
      Adding the 9p21 allele to traditional RFs in whites in the Atherosclerosis Risk
      in Communities study modestly improved CHD risk prediction in the intermediate
      categories.

PMID- 20031598
TI  - Ethical challenges encountered in genomic research.

PMID- 20031600
TI  - Pathways of the heart.

PMID- 20031601
TI  - Clinical and functional characterization of TNNT2 mutations identified in
      patients with dilated cardiomyopathy.
AB  - BACKGROUND: A key issue for cardiovascular genetic medicine is ascertaining if a
      putative mutation indeed causes dilated cardiomyopathy (DCM). This is critically
      important as genetic DCM, usually presenting with advanced, life-threatening
      disease, may be preventable with early intervention in relatives known to carry
      the mutation. METHODS AND RESULTS: We recently undertook bidirectional
      resequencing of TNNT2, the cardiac troponin T gene, in 313 probands with DCM. We
      identified 6 TNNT2 protein-altering variants in 9 probands, all who had early
      onset, aggressive disease. Additional family members of mutation carriers were
      then studied when available. Four of the 9 probands had DCM without a family
      history, and 5 probands had familial DCM. Only 1 mutation (Lys210del) could be
      attributed as definitively causative from previous reports. Four of the 5
      missense mutations were novel (Arg134Gly, Arg151Cys, Arg159Gln, and Arg205Trp),
      and one was previously reported with hypertrophic cardiomyopathy (Glu244Asp).
      Based on the clinical, pedigree, and molecular genetic data, these 5 mutations
      were considered possibly or likely disease causing. To further clarify their
      potential pathophysiologic impact, we undertook functional studies of these
      mutations in cardiac myocytes reconstituted with mutant troponin T proteins. We
      observed decreased Ca(2+) sensitivity of force development, a hallmark of DCM, in
      support of the conclusion that these mutations are disease causing. CONCLUSIONS:
      We conclude that the combination of clinical, pedigree, molecular genetic, and
      functional data strengthen the interpretation of TNNT2 mutations in DCM.

PMID- 20031602
TI  - Echocardiographic strain imaging to assess early and late consequences of
      sarcomere mutations in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Genetic testing identifies sarcomere mutation carriers (G+) before
      clinical diagnosis of hypertrophic cardiomyopathy (HCM), allowing
      characterization of initial disease manifestations. Previous studies demonstrated
      that impaired relaxation develops before left ventricular hypertrophy (LVH). The
      precise impact of sarcomere mutations on systolic function in early and late
      disease is unclear. METHODS AND RESULTS: Comprehensive echocardiography with
      strain imaging was performed on 146 genotyped individuals with mutations in 5
      sarcomere genes. Contractile parameters were compared in 68 preclinical (G+/LVH
      ), 40 overt (G+/LVH+) subjects with HCM, and 38 mutation (-) normal control
      relatives. All subjects had normal left ventricular ejection fraction. In
      preclinical HCM, global and regional peak systolic strain (epsilon(sys)) and
      longitudinal systolic strain rate were not significantly different from controls,
      but early diastolic mitral annular velocity (Ea) was reduced by 13%. In overt
      HCM, there was a significant 27% and 14% decrease in global longitudinal
      epsilon(sys) and systolic strain rate, respectively, compared with both
      preclinical HCM and controls (P<0.013 for all comparisons), and a 33% reduction
      in Ea. CONCLUSIONS: Sarcomere mutations have disparate initial effects on
      diastolic and systolic functions. Preclinical HCM is characterized by impaired
      relaxation but preserved systolic strain. In contrast, both diastolic and
      longitudinal systolic abnormalities are present in overt disease despite normal
      ejection fraction. We propose that diastolic dysfunction is an early consequence
      of sarcomere mutations, whereas systolic dysfunction results from mutations
      combined with subsequent pathological remodeling. Identifying mechanistic
      pathways triggered by these mutations may begin to reshape the clinical paradigm
      for treatment, based on early diagnosis and disease prevention.

PMID- 20031603
TI  - A genome-wide association scan of RR and QT interval duration in 3 European
      genetically isolated populations: the EUROSPAN project.
AB  - BACKGROUND: We set out to identify common genetic determinants of the length of
      the RR and QT intervals in 2325 individuals from isolated European populations.
      METHODS AND RESULTS: We analyzed the heart rate at rest, measured as the RR
      interval, and the length of the corrected QT interval for association with 318
      237 single-nucleotide polymorphisms. The RR interval was associated with common
      variants within GPR133, a G-protein-coupled receptor (rs885389, P=3.9 x 10(-8)).
      The QT interval was associated with the earlier reported NOS1AP gene (rs2880058,
      P=2.00 x 10(-10)) and with a region on chromosome 13 (rs2478333, P=4.34 x 10(
      8)), which is 100 kb from the closest known transcript LOC730174 and has
      previously not been associated with the length of the QT interval. CONCLUSIONS:
      Our results suggested an association between the RR interval and GPR133 and
      confirmed an association between the QT interval and NOS1AP.

PMID- 20031604
TI  - Genome-wide association scan identifies variants near Matrix Metalloproteinase
      (MMP) genes on chromosome 11q21-22 strongly associated with serum MMP-1 levels.
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-1 may play a role in cardiovascular
      disease susceptibility by influencing plaque rupture via its ability to degrade
      extracellular collagens. METHODS AND RESULTS: We performed a genome-wide
      association analysis of circulating MMP-1 levels using 500 K single-nucleotide
      polymorphisms (SNPs) to identify genes influencing variation in serum MMP-1
      levels in 778 healthy Amish adults. Serum MMP-1 levels, logarithm transformed,
      and adjusted for age and sex, were screened for association with SNPs using mixed
      model variance components to account for familial relatedness. Median MMP-1 level
      was 3.05 ng/mL (interquartile range: 1.82 to 5.04 ng/mL) with an estimated
      heritability of 81% (P<0.0001). Serum MMP-1 levels were strongly associated with
      a cluster of 179 SNPs extending over an 11.5-megabase region on chromosome 11q.
      The peak association was with rs495366 (P = 5.73 x 10(-34)), located within the
      region between MMP-1 and MMP-3 and having a minor allele frequency of 0.36. Two
      other SNPs within the 11q region, rs12289128 and rs11226373, were strongly
      associated with MMP-1 levels after accounting for rs495366 (P < or = 10(-7)).
      These 3 SNPs explained 31% of the variance in MMP-1 levels after adjusting for
      age and sex. CONCLUSIONS: This study provides strong evidence that the serum MMP
      1 level is highly heritable and that SNPs near MMPs on chromosome 11q explain a
      significant portion of the variation in MMP-1 levels. Identification of the
      genetic variants that influence MMP-1 levels may provide insights into genetic
      mechanisms of cardiovascular disease.

PMID- 20031605
TI  - 9p21 is a shared susceptibility locus strongly for coronary artery disease and
      weakly for ischemic stroke in Chinese Han population.
AB  - BACKGROUND: Recent studies on genome-wide association have identified common
      variants on chromosome 9p21 associated with coronary artery disease (CAD). Given
      that ischemic stroke and CAD share several aspects of etiology and pathogenesis,
      we investigated the association of variants on chromosome 9p21 with ischemic
      stroke and CAD in the Chinese Han population by capturing the majority of
      diversity in this locus using haplotype-tagging single-nucleotide polymorphisms.
      METHODS AND RESULTS: We performed a shared control-cases study using 15 tagging
      single-nucleotide polymorphisms and 2 previously reported susceptibility single
      nucleotide polymorphisms spanning 58 kb of the chromosome of 9p21 in a set of 558
      patients with ischemic stroke, 510 patients with CAD, and 557 unaffected
      participants (controls) in the Chinese Han population. The association analyses
      were performed at both SNP and haplotype levels. We further verified our findings
      in an independent cohort of 442 ischemic stroke cases and 502 control subjects.
      In the first study, rs2383206, rs1004638, and rs10757278 in block 3 were
      significantly associated with CAD but not with ischemic stroke independent of
      traditional cardiovascular risk factors in additive model (P = 0.002 to 0.0001, q
      = 0.026 to 0.004). Analysis from all blocks revealed that haplotype profiles of
      block 3 on 9p21 were significantly different between shared control and cases of
      CAD (P = 1.3 x 10(-10), q = 1.2 x 10(-9)) and ischemic stroke (P = 1.7 x 10(-6),
      q = 7.7 x 10(-6)). In the expanded second case-control study, block 3 on 9p21
      remained associated with ischemic stroke (P = 2.6 x 10(-4), q = 6.3 x 10(-4)).
      CONCLUSIONS: Our results suggest for the first time that 9p21 is a shared
      susceptibility locus, strongly for CAD and weakly for ischemic stroke, in a
      Chinese Han population.

PMID- 20031606
TI  - The 9p21 myocardial infarction risk allele increases risk of peripheral artery
      disease in older people.
AB  - BACKGROUND: A common variant at chromosome 9p21 (tagged by the rs1333049 or
      rs10757278 single-nucleotide polymorphism) is strongly associated with myocardial
      infarction and major arterial aneurysms. An association with peripheral arterial
      disease (PAD) was also reported in a sample younger than 75 years, but this
      disappeared on removal of respondents with a myocardial infarction history,
      resulting in an odds ratio of 1.09 for PAD (P=0.075). We aimed at estimating the
      association of this variant with an Ankle-Brachial Index (ABI) and PAD in 3 older
      populations. METHODS AND RESULTS: We used data from the InCHIANTI, Baltimore
      Longitudinal Study of Aging, and Health, Aging, and Body Composition studies. In
      2630 white individuals (mean age, 76.4 years), the C allele at rs1333049 was
      associated with lower mean ABI measures and with an increased prevalence of PAD.
      These associations remained after removal of baseline and incident myocardial
      infarction cases over a 6-year follow-up for both ABI (-0.017 ABI units; 95% CI, 
      0.03 to -0.01; P = 1.3 x 10(-4)) and PAD (per allele odds ratio, 1.29; 95% CI,
      1.06 to 1.56; P = 0.012). These associations also remained after adjustment for
      known atherosclerosis risk factors, including diabetes mellitus, smoking,
      hypercholesterolemia, and hypertension. CONCLUSIONS: The C allele at rs1333049 is
      associated with an increased prevalence of PAD and lower mean ABI. This
      association was independent of the presence of diagnosed myocardial infarction
      and atherosclerotic risk factors in 3 older white populations.

PMID- 20031607
TI  - Longitudinal association of PCSK9 sequence variations with low-density
      lipoprotein cholesterol levels: the Coronary Artery Risk Development in Young
      Adults Study.
AB  - BACKGROUND: Mutations of PCSK9 are associated cross-sectionally with plasma low
      density lipoprotein cholesterol (LDL-C) levels, but little is known about their
      longitudinal association with LDL-C levels from young adulthood to middle age.
      METHODS AND RESULTS: We investigated the associations of 6 PCSK9 variants with
      LDL-C over 20 years in 1750 blacks and 1828 whites from the Coronary Artery Risk
      Development In Young Adults study. Generalized estimating equations were used to
      assess longitudinal differences in LDL-C levels between genotype categories. For
      blacks, LDL-C levels at age 18 were significantly lower (P<0.001) among those
      with 3 genetic variants (L253F, C679X, and Y142X; 81.5 mg/dL) and A443T (95.5
      mg/dL) compared with noncarriers (109.6 mg/dL). The difference in LDL-C levels
      from noncarriers tended to widen for those with the 3 variants only, by 0.24
      mg/dL per year of age (P=0.14). For whites with the R46L variant, compared with
      noncarriers, LDL-C levels at age 18 were significantly lower (84.4 mg/dL versus
      100.9 mg/dL; P<0.001), and the increase in LDL-C with age was similar to
      noncarriers. The 3 genetic variants and the A443T variant in black men were
      associated with lower carotid intima-media thickness and lower prevalence of
      coronary calcification measured at ages 38 to 50. CONCLUSIONS: Our results
      suggest that participants with several genetic variants of PCSK9 have
      persistently lower serum LDL-C levels than noncarriers from ages 18 to 50. Such
      long-term reduction in LDL-C levels is associated with reduced subclinical
      atherosclerosis burden in black men.

PMID- 20031608
TI  - CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment
      response.
AB  - BACKGROUND: The gene encoding the target of calcium channel blockers, the alpha1c
      subunit of the L-type calcium channel (CACNA1C), has not been well characterized,
      and only small pharmacogenetic studies testing this gene have been published to
      date. METHODS AND RESULTS: Resequencing of CACNA1C was performed followed by a
      nested case-control study of the INternational VErapamil SR/trandolapril STudy
      (INVEST) GENEtic Substudy (INVEST-GENES). Of 46 polymorphisms identified, 8 were
      assessed in the INVEST-GENES. Rs1051375 was found to have a significant
      interaction with treatment strategy (P=0.0001). Rs1051375 A/A genotype was
      associated with a 46% reduction in the primary outcome among those randomized to
      verapamil SR treatment, when compared with atenolol treatment (odds ratio 0.54
      95% CI 0.32 to 0.92). In heterozygous A/G individuals, there was no difference in
      the occurrence of the primary outcome when randomized to verapamil SR versus
      atenolol treatment (odds ratio 1.47 95% CI 0.86 to 2.53), whereas homozygous G/G
      individuals had a greater than 4-fold increased risk of the primary outcome with
      verapamil treatment compared with those randomized to atenolol treatment (odds
      ratio 4.59 95% CI 1.67 to 12.67). We did not identify allelic expression
      imbalance or differences in mRNA expression in heart tissue by rs1051375
      genotype. CONCLUSIONS: Variation in CACNA1C is associated with treatment response
      among hypertensive patients with stable coronary artery disease. Our data suggest
      a genetically defined group of patients that benefit most from calcium channel
      blocker therapy, a group that benefits most from beta-blocker therapy, and a
      third group in which calcium channel blocker and beta-blocker therapy are
      equivalent.

PMID- 20031609
TI  - Cardiac resynchronization therapy corrects dyssynchrony-induced regional gene
      expression changes on a genomic level.
AB  - BACKGROUND: Cardiac electromechanical dyssynchrony causes regional disparities in
      workload, oxygen consumption, and myocardial perfusion within the left ventricle.
      We hypothesized that such dyssynchrony also induces region-specific alterations
      in the myocardial transcriptome that are corrected by cardiac resynchronization
      therapy (CRT). METHODS AND RESULTS: Adult dogs underwent left bundle branch
      ablation and right atrial pacing at 200 bpm for either 6 weeks (dyssynchronous
      heart failure, n=12) or 3 weeks, followed by 3 weeks of resynchronization by
      biventricular pacing at the same pacing rate (CRT, n=10). Control animals without
      left bundle branch block were not paced (n=13). At 6 weeks, RNA was isolated from
      the anterior and lateral left ventricular (LV) walls and hybridized onto canine
      specific 44K microarrays. Echocardiographically, CRT led to a significant
      decrease in the dyssynchrony index, while dyssynchronous heart failure and CRT
      animals had a comparable degree of LV dysfunction. In dyssynchronous heart
      failure, changes in gene expression were primarily observed in the anterior LV,
      resulting in increased regional heterogeneity of gene expression within the LV.
      Dyssynchrony-induced expression changes in 1050 transcripts were reversed by CRT
      to levels of nonpaced hearts (false discovery rate <5%). CRT remodeled
      transcripts with metabolic and cell signaling function and greatly reduced
      regional heterogeneity of gene expression as compared with dyssynchronous heart
      failure. CONCLUSIONS: Our results demonstrate a profound effect of
      electromechanical dyssynchrony on the regional cardiac transcriptome, causing
      gene expression changes primarily in the anterior LV wall. CRT corrected the
      alterations in gene expression in the anterior wall, supporting a global effect
      of biventricular pacing on the ventricular transcriptome that extends beyond the
      pacing site in the lateral wall.

PMID- 20031610
TI  - Proteomics, metabolomics, and immunomics on microparticles derived from human
      atherosclerotic plaques.
AB  - BACKGROUND: Microparticles (MPs) with procoagulant activity are present in human
      atherosclerosis, but no detailed information is available on their composition.
      METHODS AND RESULTS: To obtain insights into the role of MPs in atherogenesis, MP
      proteins were identified by tandem mass spectrometry, metabolite profiles were
      determined by high-resolution nuclear magnetic resonance spectroscopy, and
      antibody reactivity was assessed against combinatorial antigen libraries. Plaque
      MPs expressed surface antigens consistent with their leukocyte origin, including
      major histocompatibility complex classes I and II, and induced a dose-dependent
      stimulatory effect on T-cell proliferation. Notably, taurine, the most abundant
      free organic acid in human neutrophils, which scavenges myeloperoxidase-catalyzed
      free radicals, was highly enriched in plaque MPs. Moreover, fluorescent labeling
      of proteins on the MP surface suggested immunoglobulins to be trapped inside,
      which was confirmed by flow cytometry analysis on permeabilized and
      nonpermeabilized plaque MPs. Colabeling for CD14 and IgG established that more
      than 90% of the IgG containing MPs were CD14(+), indicating a macrophage origin.
      Screening against an antigen library revealed that the immunologic profiles of
      antibodies in MPs were similar to those found in plaques but differed profoundly
      from antibodies in plasma and unexpectedly, showed strong reactions with
      oligosaccharide antigens, in particular blood group antigen A. CONCLUSIONS: This
      study provides the first evidence that immunoglobulins are present within MPs
      derived from plaque macrophages, that the portfolio of plaque antibodies is
      different from circulating antibodies in plasma, and that anticarbohydrate
      antibodies are retained in human atherosclerotic lesions.

PMID- 20031611
TI  - Prolactin levels and the risk of future coronary artery disease in apparently
      healthy men and women.
AB  - BACKGROUND: Prolactin is increasingly recognized to play a stimulatory role in
      the inflammatory response. Because inflammation is considered of crucial
      importance in the development of atherosclerosis, we aimed to evaluate whether
      prolactin levels are associated with the occurrence of coronary artery disease
      (CAD). METHODS AND RESULTS: We performed a nested case-control study in the
      prospective EPIC-Norfolk cohort. Cases were apparently healthy men and women,
      aged 45 to 79 years, who developed fatal or nonfatal CAD (n=882). Controls
      remained free of CAD (n=1490). Overall, systemic prolactin levels did not differ
      between cases and controls, and people in the highest prolactin tertile did not
      have a significantly increased risk of developing future CAD (in men, odds ratio,
      1.21; 95% CI, 0.92 to 1.61; in women, odds ratio, 1.12; 95% CI, 0.76 to 1.64).
      However, in a separate immunohistochemical study, the presence of prolactin
      receptors could be demonstrated in postmortem human coronary artery plaques
      (preliminary data). CONCLUSIONS: Elevated systemic prolactin levels do not
      predict CAD in the general population. However, prolactin receptors were found in
      human coronary artery plaques. This observation may indicate a role of prolactin
      within atherosclerotic plaques. More studies are needed to define the possible
      role of prolactin in atherosclerotic plaque development.

PMID- 20031613
TI  - MicroRNAs in cardiovascular biology and heart disease.
AB  - MicroRNAs play important roles in many cellular and biological functions via the
      regulation of mRNA target translation. In the cardiovascular field, microRNAs are
      now acknowledged as fundamental in regulating the expression of genes that
      governs physiological and pathological myocardial adaptation to stress. Here, we
      review recent progress in the understanding of microRNA functions and their
      involvement in heart disease.

PMID- 20031612
TI  - Social- and behavioral-specific genetic effects on blood pressure traits: the
      Strong Heart Family Study.
AB  - BACKGROUND: Population studies have demonstrated an important role of social,
      behavioral, and environmental factors in blood pressure (BP) levels. Accounting
      for the genetic interaction of these factors may help to identify common BP
      susceptibility alleles. METHODS AND RESULTS: We studied the interaction of
      additive genetic effects and behavioral (physical activity, smoking, alcohol use)
      and socioeconomic (education) factors on BP in approximately 3600 American Indian
      participants of the Strong Heart Family Study, using variance component models.
      The mean and SD of resting systolic and diastolic BPs were 123 + or - 17 and 76 +
      or - 11 mm Hg, respectively. We detected evidence for distinct genetic effects on
      diastolic BP among ever smokers compared with never smokers (P = 0.01). For
      alcohol intake, we observed significant genotype-by-environment interactions on
      diastolic (rhog = 0.10, P = 0.0003) and on systolic BPs (rhog = 0.59, P = 0.0008)
      among current drinkers compared with former or never drinkers. We also detected
      genotype-by-physical activity interactions on diastolic BP (rhog = 0.35, P =
      0.0004). Finally, there was evidence for distinct genetic effects on diastolic BP
      among individuals with less than high school education compared with those with
      12 or more years of education (rhog = 0.41, P = 0.02). CONCLUSIONS: Our findings
      suggest that behavioral and socioeconomic factors can modify the genetic effects
      on BP phenotypes. Accounting for context dependent factors may help us to better
      understand the complexities of the gene effects on BP and other complex
      phenotypes with high levels of genetic heterogeneity.

PMID- 20031615
TI  - Desmosome mutations in arrhythmogenic right ventricular cardiomyopathy: important
      insight but only part of the picture.

PMID- 20031616
TI  - Desmoglein-2 and desmocollin-2 mutations in dutch arrhythmogenic right
      ventricular dysplasia/cardiomypathy patients: results from a multicenter study.
AB  - BACKGROUND: This study aimed to evaluate the prevalence and type of mutations in
      the major desmosomal genes, Plakophilin-2 (PKP2), Desmoglein-2 (DSG2), and
      Desmocollin-2 (DSC2), in arrhythmogenic right ventricular
      dysplasia/cardiomyopathy (ARVD/C) patients. We also aimed to distinguish relevant
      clinical and ECG parameters. METHODS AND RESULTS: Clinical evaluation was
      performed according to the Task Force Criteria (TFC). We analyzed the genes in
      (a) 57 patients who fulfilled the ARVD/C TFC (TFC+), (b) 28 patients with
      probable ARVD/C (1 major and 1 minor, or 3 minor criteria), and (c) 31 patients
      with 2 minor or 1 major criteria. In the TFC+ ARVD/C group, 23 patients (40%) had
      PKP2 mutations, 4 (7%) had DSG2 mutations, and 1 patient (2%) carried a mutation
      in DSC2, whereas 1 patient (2%) had a mutation in both DSG2 and DSC2. Among the
      DSG2 and DSC2 mutation-positive TFC+ ARVD/C probands, 2 carried compound
      heterozygous mutations and 1 had digenic mutations. In probable ARVD/C patients
      and those with 2 minor or 1 major criteria for ARVD/C, mutations were less
      frequent and they were all heterozygous. Negative T waves in the precordial leads
      were observed more (P<0.002) among mutation carriers than noncarriers and in
      particular in PKP2 mutation carriers. CONCLUSIONS: Mutations in DSG2 and DSC2 are
      together less prevalent (10%) than PKP2 mutations (40%) in Dutch TFC+ ARVD/C
      patients. Interestingly, biallelic or digenic DSC2 and/or DSG2 mutations are
      frequently identified in TFC+ ARVD/C patients, suggesting that a single mutation
      is less likely to cause a full-blown ARVD/C phenotype. Negative T waves on ECG
      were prevalent among mutation carriers (P<0.002).

PMID- 20031617
TI  - Comprehensive desmosome mutation analysis in north americans with arrhythmogenic
      right ventricular dysplasia/cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is
      an inherited disorder typically caused by mutations in components of the cardiac
      desmosome. The prevalence and significance of desmosome mutations among patients
      with ARVD/C in North America have not been described previously. We report
      comprehensive desmosome genetic analysis for 100 North Americans with clinically
      confirmed or suspected ARVD/C. METHODS AND RESULTS: In 82 individuals with ARVD/C
      and 18 people with suspected ARVD/C, DNA sequence analysis was performed on PKP2,
      DSG2, DSP, DSC2, and JUP. In those with ARVD/C, 52% harbored a desmosome
      mutation. A majority of these mutations occurred in PKP2. Notably, 3 of the
      individuals studied have a mutation in more than 1 gene. Patients with a
      desmosome mutation were more likely to have experienced ventricular tachycardia
      (73% versus 44%), and they presented at a younger age (33 versus 41 years)
      compared with those without a desmosome mutation. Men with ARVD/C were more
      likely than women to carry a desmosome mutation (63% versus 38%). A mutation was
      identified in 5 of 18 patients (28%) with suspected ARVD. In this smaller
      subgroup, there were no significant phenotypic differences identified between
      individuals with a desmosome mutation compared with those without a mutation.
      CONCLUSIONS: Our study shows that in 52% of North Americans with ARVD/C a
      mutation in one of the cardiac desmosome genes can be identified. Compared with
      those without a desmosome gene mutation, individuals with a desmosome gene
      mutation had earlier-onset ARVD/C and were more likely to have ventricular
      tachycardia.

PMID- 20031618
TI  - Prevalence of sarcomere protein gene mutations in preadolescent children with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) in infants and children is thought
      to be commonly associated with metabolic disorders and malformation syndromes.
      Familial disease caused by mutations in cardiac sarcomere protein genes, which
      accounts for most cases in adolescents and adults, is believed to be a very rare
      cause of HCM. METHODS AND RESULTS: Seventy-nine consecutive patients diagnosed
      with HCM aged 13 years or younger underwent detailed clinical and genetic
      evaluation. The protein-coding sequences of 9 sarcomere protein genes (MYH7,
      MYBPC3, TNNI3, TNNT2, TPM1, MYL2, MYL3, ACTC, and TNNC1), the genes encoding
      desmin (DES), and the gamma-2 subunit of AMP kinase (PRKAG2) were screened for
      mutations. A family history of HCM was present in 48 patients (60.8%). Forty
      seven mutations (15 novel) were identified in 42 (53.2%) patients (5 patients had
      2 mutations). The genes most commonly implicated were MYH7 (48.9%) and MYBPC3
      (36.2%); mutations in TNNT2, ACTC, MYL3, and TNNI3 accounted for <5% of cases
      each. A total of 16.7% patients with sarcomeric mutations were diagnosed before 1
      year of age. There were no differences in clinical and echocardiographic features
      between those children with sarcomere protein gene mutations and those without or
      between patients with 2 mutations and those with 1 or no mutations. CONCLUSIONS:
      This study shows that familial disease is common among infants and children with
      HCM and that, in most cases, disease is caused by mutations in cardiac sarcomere
      protein genes. The major implication is that all first-degree relatives of any
      child diagnosed with HCM should be offered screening. Furthermore, the finding
      that one sixth of patients with sarcomeric disease were diagnosed in infancy
      suggests that current views on pathogenesis and natural history of familial HCM
      may have to be revised.

PMID- 20031619
TI  - Sarcomere mutations in cardiomyopathy with left ventricular hypertrabeculation.
AB  - BACKGROUND: Mutations in the genes encoding sarcomere proteins have been
      associated with both hypertrophic and dilated cardiomyopathy. Recently, mutations
      in myosin heavy chain (MYH7), cardiac actin (ACTC), and troponin T (TNNT2) were
      associated with left ventricular noncompaction, a form of cardiomyopathy
      characterized with hypertrabeculation that may also include reduced function of
      the left ventricle. METHODS AND RESULTS: We used clinically available genetic
      testing on 3 cases referred for evaluation of left ventricular dysfunction and
      noncompaction of the left ventricle and found that all 3 individuals carried
      sarcomere mutations. The first patient presented with neonatal heart failure and
      was referred for left ventricular noncompaction cardiomyopathy. Genetic testing
      found 2 different mutations in MYBPC3 in trans. The first mutation, 3776delA,
      Q1259fs, rendered a frame shift at 1259 of cardiac myosin-binding protein C and
      the second mutation was L1200P. The frameshift mutation was also found in this
      mother who displayed mild echocardiographic features of cardiomyopathy, with only
      subtle increase in trabeculation and an absence of hypertrophy. A second
      pediatric patient presented with heart failure and was found to carry a de novo
      MYH7 R369Q mutation. The third case was an adult patient with dilated
      cardiomyopathy referred for ventricular hypertrabeculation. This patient had a
      family history of congestive heart failure, including pediatric onset
      cardiomyopathy where 3 individuals in the family were found to have the MYH7
      mutation R1250W. CONCLUSIONS: Genetic testing should be considered for
      cardiomyopathy with hypertrabeculation.

PMID- 20031621
TI  - Distinct early signaling events resulting from the expression of the PRKAG2 R302Q
      mutant of AMPK contribute to increased myocardial glycogen.
AB  - BACKGROUND: Humans with an R302Q mutation in AMPKgamma(2) (the PRKAG2 gene)
      develop a glycogen storage cardiomyopathy characterized by a familial form of
      Wolff-Parkinson-White syndrome and cardiac hypertrophy. This phenotype is
      recapitulated in transgenic mice with cardiomyocyte-restricted expression of
      AMPKgamma(2)R302Q. Although considerable information is known regarding the
      consequences of harboring the gamma(2)R302Q mutation, little is known about the
      early signaling events that contribute to the development of this cardiomyopathy.
      METHODS AND RESULTS: To distinguish the direct effects of gamma(2)R302Q
      expression from later compensatory alterations in signaling, we used transgenic
      mice expressing either the wild-type AMPKgamma(2) subunit (TGgamma(2)WT) or the
      mutated form (TGgamma(2)R302Q), in combination with acute expression of these
      proteins in neonatal rat cardiomyocytes. Although acute expression of
      gamma(2)R302Q induces AMPK activation and upregulation of glycogen synthase and
      AS160, with an associated increase in glycogen content, AMPK activity, glycogen
      synthase activity, and AS160 expression are reduced in hearts from
      TGgamma(2)R302Q mice, likely in response to the existing 37-fold increase in
      glycogen. Interestingly, gamma(2)WT expression has similar, yet less marked
      effects than gamma(2)R302Q expression in both cardiomyocytes and hearts.
      CONCLUSIONS: Using acute and chronic models of gamma(2)R302Q expression, we have
      differentiated the direct effects of the gamma(2)R302Q mutation from eventual
      compensatory modifications. Our data suggest that expression of gamma(2)R302Q
      induces AMPK activation and the eventual increase in glycogen content, a finding
      that is masked in hearts from transgenic adult mice. These findings are the first
      to highlight temporal differences in the effects of the PRKAG2 R302Q mutation on
      cardiac metabolic signaling events.

PMID- 20031620
TI  - High incidence of the cardiac variant of Fabry disease revealed by newborn
      screening in the Taiwan Chinese population.
AB  - BACKGROUND: Fabry disease is a treatable lysosomal storage disorder, which is
      often misdiagnosed or belatedly diagnosed. METHODS AND RESULTS: To determine the
      disease incidence in the Taiwan Chinese population, a Fabry disease newborn
      screening study was initiated. A total of 110 027 newborns were screened by
      assaying the alpha-galactosidase A (alpha-Gal A) activity using dry blood spots.
      Low plasma alpha-Gal A activity and presence of a Fabry mutation was demonstrated
      in 45 neonates (3 females). Eight different mutations were identified, including
      3 known missense mutations (R112H, A143T, and R356W), 4 novel missense mutations
      (G104V, M296L, G360C, and K391T), and one known intronic mutation (IVS4+919G-
      >A). The IVS4+919G-->A mutation was most common (82% of patients). A total of 20
      maternal grandparents of infants harboring this intronic mutation were evaluated
      by echocardiography, mutation analysis and alpha-Gal A activity assay. The
      intronic mutation was found in 9 grandfathers and 11 grandmothers. Of these
      grandparents, 3 grandfathers (33%) but none of the grandmothers had hypertrophic
      cardiomyopathy. Additionally, 16 males who had been diagnosed with idiopathic
      hypertrophic cardiomyopathy were screened by mutation analysis and alpha-Gal A
      activity; 4 (25%) showed deficient plasma alpha-Gal A activity in combination
      with the intronic mutation. CONCLUSIONS: We found an unexpected high prevalence
      of the cardiac variant Fabry mutation IVS4+919G-->A among both newborns
      (approximately 1 in 1600 males) and patients with idiopathic hypertrophic
      cardiomyopathy in the Taiwan Chinese population. The early identification of
      undiagnosed patients allows timely therapeutic intervention providing a better
      clinical outcome.

PMID- 20031622
TI  - Genetic variation at the proprotein convertase subtilisin/kexin type 5 gene
      modulates high-density lipoprotein cholesterol levels.
AB  - BACKGROUND: A low level of plasma high-density lipoprotein cholesterol (HDL-C) is
      a risk factor for cardiovascular disease. HDL particles are modulated by a
      variety of lipases, including endothelial lipase, a phospholipase present on
      vascular endothelial cells. The proprotein convertase subtilisin/kexin type 5
      (PCSK5) gene product is known to directly inactivate endothelial lipase and
      indirectly cleave and activate angiopoetin-like protein 3, a natural inhibitor of
      endothelial lipase. We therefore investigated the effect of human PCSK5 genetic
      variants on plasma HDL-C levels. METHODS AND RESULTS: Haplotypes at the PCSK5
      locus were examined in 9 multigenerational families that included 60 individuals
      with HDL-C <10th percentile. Segregation with low HDL-C in 1 family was found.
      Sequencing of the PCSK5 gene in 12 probands with HDL-C <5th percentile identified
      7 novel variants. Using a 2-stage design, we first genotyped these single
      nucleotide polymorphisms (SNPs) along with 163 tagSNPs and 12 additional SNPs
      (n=182 total) in 457 individuals with documented coronary artery disease. We
      identified 9 SNPs associated with HDL-C (P<0.05), with the strongest results for
      rs11144782 and rs11144766 (P=0.002 and P=0.005, respectively). The SNP rs11144782
      was also associated with very low-density lipoprotein (P=0.039), triglycerides
      (P=0.049), and total apolipoprotein levels (P=0.022). In stage 2, we replicated
      the association of rs11144766 with HDL-C (P=0.014) in an independent sample of
      Finnish low HDL-C families. In a combined analysis of both stages (n=883), region
      wide significance of rs11144766 and low HDL-C was observed (unadjusted P=1.86x10(
      4) and Bonferroni-adjusted P=0.031). CONCLUSIONS: We conclude that variability at
      the PCSK5 locus influences HDL-C levels, possibly through the inactivation of
      endothelial lipase activity, and, consequently, atherosclerotic cardiovascular
      disease risk.

PMID- 20031623
TI  - EPHB4 gene polymorphisms and risk of intracranial hemorrhage in patients with
      brain arteriovenous malformations.
AB  - BACKGROUND: Brain arteriovenous malformations (BAVMs) are a tangle of abnormal
      vessels directly shunting blood from the arterial to venous circulation and an
      important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial
      venous determination during embryogenesis; altered signaling could lead to
      vascular instability resulting in ICH. We investigated the association of single
      nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at
      clinical presentation in patients with BAVM. METHODS AND RESULTS: Eight haplotype
      tagging SNPs spanning approximately 29 kb were tested for association with ICH
      presentation in 146 white patients with BAVM (phase I: 56 ICH, 90 non-ICH) using
      allelic, haplotypic, and principal components analysis. Associated SNPs were then
      genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH), and data were
      combined for multivariable logistic regression. Minor alleles of 2 SNPs were
      associated with reduced risk of ICH presentation (rs314313_C, P=0.005;
      rs314308_T, P=0.0004). Overall, haplotypes were also significantly associated
      with ICH presentation (chi(2)=17.24, 6 df, P=0.008); 2 haplotypes containing the
      rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with
      reduced risk. In principal components analysis, 2 components explained 91% of the
      variance and complemented haplotype results by implicating 4 SNPs at the 5' end,
      including rs314308 and rs314313. These 2 SNPs were replicated in the phase II
      cohort, and combined data resulted in greater significance (rs314313, P=0.0007;
      rs314308, P=0.00008). SNP association with ICH presentation persisted after
      adjusting for age, sex, BAVM size, and deep venous drainage. CONCLUSIONS: EPHB4
      polymorphisms are associated with risk of ICH presentation in patients with BAVM,
      warranting further study.

PMID- 20031624
TI  - A common copy number variation on chromosome 6 association with the gene
      expression level of endothelin 1 in transformed B lymphocytes from three racial
      groups.
AB  - BACKGROUND: Previous studies indicate that the endothelin system is involved in
      hypertension, heart failure, atherosclerosis, chronic kidney disease, and
      diabetes. To explore the potential genetic effects of copy number variations
      (CNVs) on the endothelin system, which underlie these diseases, we studied the
      association of genome-wide CNVs with gene expression levels of 7 genes involved
      in the endothelin system using independent HapMap subjects including 90 Asians
      (45 Han Chinese and 45 Japanese), 60 whites, and 60 blacks. METHODS AND RESULTS:
      For each subject, the genome-wide variations were measured using the Affymetrix
      6.0 chip that includes measurements of 906 000 single-nucleotide polymorphisms
      and 946 000 CNV probes. The gene expression profiles of the transformed B
      lymphocytes were measured for the same subjects. Among the 210 subjects, we
      identified 1529 CNV regions on 22 autosomes. By testing the association between
      CNVs and the gene expression levels in each racial group using linear regression,
      we identified 4 statistically significant CNV associations in all 3 groups
      (alpha=0.05). The strongest association was between a 66 kbp CNV region located
      on chromosome 6 and endothelin-1 (EDN1) expression. The effects of the CNV-EDN1
      association in the 3 racial groups were in the same direction and explained 7% to
      14% of the variation in EDN1 expression. CONCLUSIONS: Although the biological
      function of the chromosome 6 CNV is unclear, the significant and consistent
      association found in 3 racial groups suggests that CNVs may contribute to
      variation in underlying risks of common disease through their effects on key
      molecular signaling pathways.

PMID- 20031625
TI  - Refining molecular pathways leading to calcific aortic valve stenosis by studying
      gene expression profile of normal and calcified stenotic human aortic valves.
AB  - BACKGROUND: Calcific aortic valve stenosis (AS) is a major societal and economic
      burden that is rising after the current shift toward an older population.
      Understanding the pathobiology of AS is crucial to implementing better preventive
      and therapeutic options. Research conducted during the past decade clearly points
      to active molecular and cellular processes involved in disease pathogenesis.
      However, no genomic approaches were used to identify genes and pathways that are
      differentially regulated in aortic valves of patients with and without AS.
      METHODS AND RESULTS: A large-scale quantitative measurements of gene expression
      was performed on 5 normal and 5 AS valves using Affymetrix GeneChips. A total of
      409 and 306 genes were significantly up- and downregulated in AS valves,
      respectively. The 2 most highly upregulated genes were matrix metalloproteinase
      12 and chitinase 3-like 1. The upregulation of these 2 biologically relevant
      genes in AS was validated by real-time polymerase chain reaction in 38 aortic
      valves (12 normal and 26 AS). To provide a global biological validation of the
      whole-genome gene expression analysis, the microarray experiment was repeated in
      a second set of aortic valves with (n=5) or without (n=5) AS. There was an
      overrepresentation of small P values among genes claimed significant in the first
      microarray experiment. A total of 223 genes were replicated (P<0.05 and fold
      change >1.2), including matrix metalloproteinase 12 and chitinase 3-like 1.
      CONCLUSIONS: This study reveals many unrecognized genes potentially implicated in
      the pathogenesis of AS. These new genes were overlaid on known pathological
      pathways leading to AS to refine our molecular understanding of this disease.

PMID- 20031627
TI  - Alcohol intake, myocardial infarction, biochemical risk factors, and alcohol
      dehydrogenase genotypes.
AB  - BACKGROUND: The risk of myocardial infarction is lower among light-to-moderate
      alcohol drinkers compared with abstainers. We tested associations between alcohol
      intake and risk of myocardial infarction and risk factors and whether these
      associations are modified by variations in alcohol dehydrogenases. METHODS AND
      RESULTS: We used information on 9584 men and women from the Danish general
      population in the Copenhagen City Heart Study. During follow-up, from 1991 to
      2007, 663 incident cases of myocardial infarction occurred. We observed that
      increasing alcohol intake was associated with decreasing risk of myocardial
      infarction, decreasing low-density lipoprotein cholesterol and fibrinogen,
      increasing diastolic and systolic blood pressure and high-density lipoprotein
      cholesterol, and with U-shaped nonfasting triglycerides. In contrast, ADH1B and
      ADH1C genotypes were not associated with risk of myocardial infarction or with
      any of the cardiovascular biochemical risk factors, and there was no indication
      that associations between alcohol intake and myocardial infarction and between
      alcohol intake and risk factors were modified by genotypes. CONCLUSIONS:
      Increasing alcohol intake is associated with decreasing risk of myocardial
      infarction, decreasing low-density lipoprotein cholesterol and fibrinogen,
      increasing diastolic and systolic blood pressure and high-density lipoprotein
      cholesterol, and U-shaped nonfasting triglycerides. These associations were not
      modified by ADH1B and ADH1C are genotypes.

PMID- 20031628
TI  - Common variation in the platelet receptor P2RY12 gene is associated with residual
      on-clopidogrel platelet reactivity in patients undergoing elective percutaneous
      coronary interventions.
AB  - BACKGROUND: The clinical efficacy of clopidogrel is hampered by a large
      interindividual variability in platelet inhibition. Polymorphisms in the P2RY12
      receptor gene have been suggested to contribute to this variability, but previous
      studies included a relatively small number of patients and incompletely covered
      the common variation in the P2RY12 gene. The aim of this study was to
      comprehensively investigate the possible association between common variation in
      the entire P2RY12 locus and the magnitude of residual on-clopidogrel platelet
      reactivity measured by 2 commonly used platelet function assays in a large cohort
      of patients. METHODS AND RESULTS: A total of 1031 consecutive patients with
      coronary artery disease who were scheduled for elective percutaneous coronary
      interventions were enrolled. Platelet function was assessed by means of ADP
      induced light-transmittance aggregometry and the VerifyNow P2Y12 assay. Six
      haplotype-tagging single nucleotide polymorphisms were carefully selected to
      comprehensively cover the total common variation in the P2RY12 gene and its
      flanking regulatory regions. Six common haplotypes were inferred from these
      haplotype-tagging single nucleotide polymorphisms (denoted A to F). Haplotype F
      was associated with significantly lower residual on-clopidogrel platelet
      reactivity compared with the reference haplotype A. The size of this effect per
      haplotype allele was approximately 5% aggregation in the ADP-induced light
      transmittance aggregometry (P<0.05) and 11 P2Y12 reaction units in the VerifyNow
      P2Y12 assay (P<0.05). CONCLUSIONS: Common variation in the P2RY12 gene is a
      significant determinant of the interindividual variability in residual on
      clopidogrel platelet reactivity in patients with coronary artery disease.

PMID- 20031626
TI  - Variation in the 4q25 chromosomal locus predicts atrial fibrillation after
      coronary artery bypass graft surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common adverse event following
      coronary artery bypass graft surgery. A recent study identified chromosome 4q25
      variants associated with AF in ambulatory populations. However, their role in
      postoperative AF is unknown. We hypothesized that genetic variants in the 4q25
      chromosomal region are independently associated with postoperative AF after
      coronary artery bypass graft surgery. METHODS AND RESULTS: Two prospectively
      collected cohorts of patients undergoing coronary artery bypass graft surgery,
      with or without concurrent valve surgery, at 3 US centers. From a discovery
      cohort of 959 patients, clinical and genomic multivariate predictors of
      postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms
      (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately
      collected validation cohort of 494 patients. After adjustment for clinical
      predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308,
      and 5 other linked SNPs independently predicted postoperative AF in the discovery
      cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57
      and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were
      measured and replicated for rs2200733 and rs13143308 in the validation cohort.
      CONCLUSIONS: In 2 independently collected cardiac surgery cohorts, noncoding SNPs
      within the chromosome 4q25 region are independently associated with postoperative
      AF after coronary artery bypass graft surgery after adjusting for clinical
      covariates and multiple comparisons.

PMID- 20031629
TI  - Functional variant disrupts insulin induction of USF1: mechanism for USF1
      associated dyslipidemias.
AB  - BACKGROUND: The upstream transcription factor 1 (USF1) gene is associated with
      familial combined hyperlipidemia, the most common genetic dyslipidemia in humans,
      as well as with various dyslipidemic changes in numerous other studies. Typical
      of complex disease-associated genes, neither the explicit mutations have been
      described nor the functional consequences for risk allele carriers been reported
      at the cellular or tissue level. METHODS AND RESULTS: In this study, we aimed at
      describing the molecular mechanism through which the strongest associating
      intronic single-nucleotide polymorphism variant in USF1 is involved in the
      development of dyslipidemia. The effects of the risk variant on gene expression
      were studied in 2 relevant human tissues, fat and muscle. Global transcript
      profiles of 47 fat biopsies ascertained for carriership of the risk allele were
      tested for differential expression of known USF1 target genes as well as for
      broader effects on the transcript profile. Allelic imbalance of USF1 in fat was
      assessed using a quantitative sequencing approach. The possible allele-specific
      effect of insulin on the expression of USF1 was studied in 118 muscle biopsies
      before and after a euglycemic hyperinsulinemic clamp. The risk allele of single
      nucleotide polymorphism rs2073658 seems to eradicate the inductive effect of
      insulin on the expression of USF1 in muscle and fat. The expression of numerous
      target genes is in turn perturbed in adipose tissue. CONCLUSIONS: In risk allele
      carriers, a defective response of USF1 to insulin results in the suboptimal
      response of relevant target genes that contributes to the enhanced risk of
      developing dyslipidemia and coronary heart disease.

PMID- 20031630
TI  - Single-nucleotide polymorphism bioinformatics: a comprehensive review of
      resources.

PMID- 20031631
TI  - Nature's genetic gradients and the clinical phenotype.

PMID- 20031632
TI  - Genetic ancestry, population admixture, and the genetic epidemiology of complex
      disease.

PMID- 20031633
TI  - Analysis of dystrophin deletion mutations predicts age of cardiomyopathy onset in
      becker muscular dystrophy.
AB  - BACKGROUND: Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy
      often result from deletion mutations in the dystrophin gene that may lead to
      expression of an altered dystrophin protein in cardiac muscle. Cardiac
      involvement is present in approximately 70% of BMD and all X-linked dilated
      cardiomyopathy cases. To date, the timing of cardiomyopathy development remains
      unpredictable. We analyzed 78 BMD and X-linked dilated cardiomyopathy patients
      with common deletion mutations predicted to alter the dystrophin protein and
      correlated their mutations to cardiomyopathy age of onset. This approach was
      chosen to connect dystrophin structure with function in the heart. METHODS AND
      RESULTS: Detailed cardiac information was collected for BMD and X-linked dilated
      cardiomyopathy patients with defined dystrophin gene deletion mutations. Patients
      were grouped based on the dystrophin protein domain affected by the deletion.
      Deletions affecting the amino-terminal domain are associated with early-onset
      dilated cardiomyopathy (DCM; mid-20s), whereas deletions removing part of the rod
      domain and hinge 3 have a later-onset DCM (mid-40s). Further, we modeled the
      effects of the most common mutations occurring in the rod domain on the overall
      structure of the dystrophin protein. By combining genetic and protein
      information, this analysis revealed a strong correlation between specific protein
      structural modifications and DCM age of onset. CONCLUSIONS: We identified
      specific regions of the dystrophin gene that when mutated predispose BMD patients
      to early-onset DCM. In addition, we propose that some mutations lead to early
      onset DCM by specific alterations in protein folding. These findings have
      potential implications for early intervention in the cardiac care of BMD patients
      and for therapeutic approaches that target the heart in dystrophinopathies.

PMID- 20031634
TI  - SCN5A mutations and the role of genetic background in the pathophysiology of
      Brugada syndrome.
AB  - BACKGROUND: Mutations in SCN5A are identified in approximately 20% to 30% of
      probands affected by Brugada syndrome (BrS). However, in familial studies, the
      relationship between SCN5A mutations and BrS remains poorly understood. The aim
      of this study was to investigate the association of SCN5A mutations and BrS in a
      group of large genotyped families. METHODS AND RESULTS: Families were included if
      at least 5 family members were carriers of the SCN5A mutation, which was
      identified in the proband. Thirteen large families composed of 115 mutation
      carriers were studied. The signature type I ECG was present in 54 mutation
      carriers (BrS-ECG+; 47%). In 5 families, we found 8 individuals affected by BrS
      but with a negative genotype (mutation-negative BrS-ECG+). Among these 8 mutation
      negative BrS-ECG+ individuals, 3, belonging to 3 different families, had a
      spontaneous type I ECG, whereas 5 had a type I ECG only after the administration
      of sodium channel blockers. One of these 8 individuals had also experienced
      syncope. Mutation carriers had, on average, longer PR and QRS intervals than
      noncarriers, demonstrating that these mutations exerted functional effects.
      CONCLUSIONS: Our results suggest that SCN5A mutations are not directly causal to
      the occurrence of a BrS-ECG+ and that genetic background may play a powerful role
      in the pathophysiology of BrS. These findings add further complexity to concepts
      regarding the causes of BrS, and are consistent with the emerging notion that the
      pathophysiology of BrS includes various elements beyond mutant sodium channels.

PMID- 20031635
TI  - Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome
      population.
AB  - BACKGROUND: A 10% cumulative incidence and a 0.3% per year incidence rate of
      sudden cardiac death in patients younger than 40 years and without therapy have
      been reported in type 1 long-QT syndrome. The Y111C-KCNQ1 mutation causes a
      severe phenotype in vitro, suggesting a high-risk mutation. This study
      investigated the phenotype among Y111C-KCNQ1 mutation carriers in the Swedish
      population with a focus on life-threatening cardiac events. METHODS AND RESULTS:
      We identified 80 mutation carriers in 15 index families, segregating the Y111C
      KCNQ1 mutation during a national inventory of mutations causing the long-QT
      syndrome. Twenty-four mutation carriers <40 years experienced syncope (30%). One
      mutation carrier had an aborted cardiac arrest (1.25%). No case of sudden cardiac
      death was reported during a mean nonmedicated follow-up of 25+/-20 years. This
      corresponds to a low incidence rate of life-threatening cardiac events
      (0.05%/year versus 0.3%/year, P=0.025). In 8 Y111C families connected by a common
      ancestor, the natural history of the mutation was assessed by investigating the
      survival over the age of 40 years for 107 nonmedicated ascertained mutation
      carriers (n=24) and family members (n=83) born between 1873 and 1968. In total, 4
      deaths in individuals younger than 40 years were noted: 1 case of noncardiac
      death and 3 infant deaths between 1873 and 1915. CONCLUSIONS: The dominant
      negative Y111C-KCNQ1 mutation, associated with a severe phenotype in vitro,
      presents with a low incidence of life-threatening cardiac events in a Swedish
      population. This finding of discrepancy emphasizes the importance of clinical
      observations in the risk stratification of long-QT syndrome.

PMID- 20031636
TI  - Binding sites for ETS family of transcription factors dominate the promoter
      regions of differentially expressed genes in abdominal aortic aneurysms.
AB  - BACKGROUND: Previously, we identified 3274 distinct differentially expressed
      genes in abdominal aortic aneurysm (AAA) tissue compared with nonaneurysmal
      controls. As transcriptional control is responsible for these expression changes,
      we sought to find common transcriptional elements in the promoter regions of the
      differentially expressed genes. METHODS AND RESULTS: We analyzed the up- and
      downregulated gene sets with Whole Genome rVISTA to determine the transcription
      factor (TF) binding sites overrepresented in the 5-kb promoter regions of the
      3274 genes. The downregulated gene set yielded 144 TF binding sites that were
      overrepresented in the subset when compared with the entire genome. In contrast,
      the upregulated gene set yielded only 13 distinct overrepresented TF binding
      sites. Interestingly, as classified by TRANSFAC, 8 of the 13 TFs binding to these
      regions belong to the ETS family. Additionally, nuclear factor kB and its
      subunits p50 and p65 showed enrichment. Immunohistochemical analyses of 10 TFs
      from the upregulated set showed 9 to be present in AAA tissue. Based on gene
      ontology analysis of biological process categories of the upregulated target
      genes of enriched TFs, 10 TFs had enrichment in immune system process among their
      target genes. CONCLUSIONS: Our genome-wide analysis provides further evidence of
      ETS and nuclear factor kB involvement in AAA. Additionally, our results provide
      novel insight for future studies aiming to dissect the pathogenesis of AAA and
      have uncovered potential therapeutic targets for AAA prevention.

PMID- 20031637
TI  - Disruption of the aortic elastic lamina and medial calcification share genetic
      determinants in mice.
AB  - BACKGROUND: Disruption of the elastic lamina, as an early indicator of aneurysm
      formation, and vascular calcification frequently occur together in
      atherosclerotic lesions of humans. METHODS AND RESULTS: We now report evidence of
      shared genetic basis for disruption of the elastic lamina (medial disruption) and
      medial calcification in an F(2) mouse intercross between C57BL/6J and C3H/HeJ on
      a hyperlipidemic apolipoprotein E (ApoE(-/-)) null BACKGROUND: gene, known to
      mediate myocardial calcification. Using transgenic complementation, we show that
      Abcc6 also contributes to aortic medial calcification. CONCLUSIONS: Our data
      indicate that calcification, though possibly contributory, does not always lead
      to medial disruption and that in addition to aneurysm formation, medial
      disruption may be the precursor to calcification.

PMID- 20031638
TI  - In vivo genetic evidence for suppressing vascular and soft-tissue calcification
      through the reduction of serum phosphate levels, even in the presence of high
      serum calcium and 1,25-dihydroxyvitamin d levels.
AB  - BACKGROUND: Klotho-knockout mice (klotho(-/-)) have increased renal expression of
      sodium/phosphate cotransporters (NaPi2a), associated with severe
      hyperphosphatemia. Such serum biochemical changes in klotho(-/-) mice lead to
      extensive soft-tissue anomalies and vascular calcification. To determine the
      significance of increased renal expression of the NaPi2a protein and concomitant
      hyperphosphatemia and vascular calcification in klotho(-/-) mice, we generated
      klotho and NaPi2a double-knockout (klotho(-/-)/NaPi2a(-/-)) mice. METHODS AND
      RESULTS: Genetic inactivation of NaPi2a activity from klotho(-/-) mice reversed
      the severe hyperphosphatemia to mild hypophosphatemia or normophosphatemia.
      Importantly, despite significantly higher serum calcium and 1,25-dihydroxyvitamin
      D levels in klotho(-/-)/NaPi2a(-/-) mice, the vascular and soft-tissue
      calcifications were reduced. Extensive soft-tissue anomalies and cardiovascular
      calcification were consistently noted in klotho(-/-) mice by 6 weeks of age;
      however, these vascular and soft-tissue abnormalities were absent even in 12-week
      old double-knockout mice. Klotho(-/-)/NaPi2a(-/-) mice also regained body weight
      and did not develop the generalized tissue atrophy often noted in klotho(-/-)
      single-knockout mice. CONCLUSIONS: Our in vivo genetic manipulation studies have
      provided compelling evidence for a pathological role of increased NaPi2a
      activities in regulating abnormal mineral ion metabolism and soft-tissue
      anomalies in klotho(-/-) mice. Notably, our results suggest that serum phosphate
      levels are the important in vivo determinant of calcification and that lowering
      serum phosphate levels can reduce or eliminate soft-tissue and vascular
      calcification, even in presence of extremely high serum calcium and 1,25
      dihydroxyvitamin D levels. These in vivo observations have significant clinical
      importance and therapeutic implications for patients with chronic kidney disease
      with cardiovascular calcification.

PMID- 20031639
TI  - A locus mapping to mouse chromosome 7 determines infarct volume in a mouse model
      of ischemic stroke.
AB  - BACKGROUND: In a mouse model of focal cerebral ischemia, infarct volume is highly
      variable and strain dependent, but the natural genetic determinants responsible
      for this difference remain unknown. To identify genetic determinants regulating
      ischemic neuronal damage and to dissect apart the role of individual genes and
      physiological mechanisms in infarction in mice, we performed quantitative trait
      locus analysis of surgically induced cerebral infarct volume. METHODS AND
      RESULTS: After permanent occlusion of the distal middle cerebral artery, infarct
      volume was determined for 16 inbred strains of mice, chromosome substitution
      strains, and for 2 intercross cohorts, F2 (B6xBALB/c) and F2 (B6xSWR/J). Genome
      wide linkage analysis was performed for infarct volume as a quantitative trait.
      Infarct volume varied up to 30-fold between strains, with heritability estimated
      at 0.88. Overall, 3 quantitative trait locus were identified that modulate
      infarct volume, with a major locus (Civq1) on chromosome 7 accounting for >50% of
      the variation, with a combined LOD score of 21.7. Interval-specific single
      nucleotide polymorphism haplotype analysis for Civq1 results in 12 candidate
      genes. CONCLUSIONS: The extent of ischemic tissue damage after distal middle
      cerebral artery occlusion in inbred strains of mice is modulated by genetic
      variation mapping to at least 3 different loci. A single locus on chromosome 7
      determines the majority of the observed variation in the trait. This locus seems
      to be identical to LSq1, a locus conferring limb salvage and reperfusion in a
      mouse model of hindlimb ischemia. The identification of the genes underlying
      these loci may uncover novel genetic and physiological pathways that modulate
      cerebral infarction and provide new targets for therapeutic intervention in
      ischemic stroke, and possibly other ischemic diseases.

PMID- 20031640
TI  - Single nucleotide polymorphisms in homocysteine metabolism pathway genes:
      association of CHDH A119C and MTHFR C677T with hyperhomocysteinemia.
AB  - BACKGROUND: An elevated level of homocysteine (hyperhomocysteinemia) has been
      implicated as an independent risk factor for cardiovascular diseases. Deficiency
      of dietary factors like vitamin B(12), folate, and genetic variations can cause
      hyperhomocysteinemia. The prevalence of hyperhomocysteinemia in the Indian
      population is likely to be high because most Indians adhere to a vegetarian diet,
      deficient in vitamin B(12). In the BACKGROUND: deficiency, variations in genes
      involved in homocysteine metabolism might have a greater impact on homocysteine
      levels. METHODS AND RESULTS: We genotyped 44 nonsynonymous single-nucleotide
      polymorphisms (nsSNPs) from 11 genes involved in homocysteine metabolism and
      found only 14 to be polymorphic. These 14 nsSNPs were genotyped in 546
      individuals recruited from a tertiary care center in New Delhi, India, and it was
      found that choline dehydrogenase (CHDH A119C) and methylenetetrahydrofolate
      reductase (MTHFR C677T) were significantly associated with plasma total
      homocysteine levels (P=0.009 and P=0.001, respectively). These 2 SNPs were
      further genotyped in 330 individuals recruited from the same center, and the
      association remained significant even after increasing the sample size.
      Furthermore, we found the possibility of a significant interaction between
      vegetarian diet and the 2 polymorphisms that could explain the variation of
      homocysteine levels. We also genotyped all the polymorphic nsSNPs in apparently
      healthy individuals recruited from 24 different subpopulations (based on their
      linguistic lineage) spread across the country to determine their basal
      frequencies. The frequencies of these SNPs varied significantly between
      linguistic groups. CONCLUSIONS: Vegetarian diet along with CHDH A119C and MTHFR
      C677T play an important role in modulating the homocysteine levels in Indian
      population.

PMID- 20031641
TI  - Association of AHSG gene polymorphisms with fetuin-A plasma levels and
      cardiovascular diseases in the EPIC-Potsdam study.
AB  - BACKGROUND: Elevated circulating levels of fetuin-A in blood have been associated
      with increased risk of cardiovascular disease. The goal of our study was to
      prospectively investigate the potential causal nature of the association between
      fetuin-A levels and myocardial infarction (MI) and ischemic stroke by applying a
      Mendelian randomization approach. METHODS AND RESULTS: Five tagging single
      nucleotide polymorphisms (rs2248690, rs2070633, rs2070635, rs4917, and rs6787344)
      capturing the common genetic variation of the fetuin-A coding gene alpha(2)
      Heremans-Schmid glycoprotein (AHSG) were genotyped in a case-cohort comprising
      214 MI cases, 154 ischemic stroke cases, and 2152 persons who remained free of
      cardiovascular disease events in the European Prospective Investigation into
      Cancer and Nutrition-Potsdam study. One single-nucleotide polymorphism
      (rs6787344) was discarded because of Hardy-Weinberg disequilibrium. All AHSG
      tagging single-nucleotide polymorphisms were associated with fetuin-A plasma
      levels (P<0.0001). AHSG rs4917 C>T showed the strongest association, explaining
      21.2% of the phenotypic variance independent of potential confounding factors
      (+35.5 microg/mL increase per C-allele, P= 2 x 10(-121)). Furthermore, the rs4917
      C-allele showed a significant association with MI (adjusted hazard rate ratio
      [RR] 1.34, 95% CI 1.05 to 1.70, P=0.02). Based on this association, the expected
      RR for MI corresponding to 1 SD in fetuin-A was 1.54 and, thus, strikingly
      matches the previously observed association between fetuin-A plasma levels and MI
      risk (RR 1.59). CONCLUSIONS: These data provide evidence for the causal nature of
      the recently reported association between fetuin-A plasma levels and MI risk,
      thereby suggesting an involvement of fetuin-A in the pathogenesis of
      cardiovascular disease.

PMID- 20031642
TI  - Serotonin transporter gene, depressive symptoms, and interleukin-6.
AB  - BACKGROUND: We explored the relationship of genetic variants of the serotonin
      transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission,
      with both depressive symptoms and plasma interleukin-6 (IL-6) levels. METHODS AND
      RESULTS: We genotyped 20 polymorphisms in 360 male twins (mean age, 54 years)
      from the Vietnam Era Twin Registry. Current depressive symptoms were measured
      with the Beck Depression Inventory II. IL-6 was assessed using a commercially
      available ELISA kit. Genotype associations were analyzed using generalized
      estimating equations. To study how SLC6A4 genetic vulnerability influences the
      relationship between depressive symptoms and IL-6, bivariate models were
      constructed using structural equation modeling. Of the 20 polymorphisms examined,
      the effective number of independent tests was 6, and the threshold of
      significance after Bonferroni correction was 0.008. There were 6 single
      nucleotide polymorphisms significantly associated with Beck Depression Inventory
      (P< or =0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122, and
      rs8076005, and 1 single-nucleotide polymorphism was borderline associated
      (rs12150214, P=0.017). Of these 7 single-nucleotide polymorphisms, 3 were also
      significantly associated with IL-6 (P<0.008), including rs25528, rs6354, and
      rs8076005, and the other 4 were borderline associated (P=0.009 to 0.025). The
      subjects with 1 copy of the minor allele of these 7 single-nucleotide
      polymorphisms had higher Beck Depression Inventory scores and IL-6 levels.
      Further bivariate modeling revealed that approximately 10% of the correlation
      between Beck Depression Inventory and IL-6 could be explained by the SLC6A4 gene.
      CONCLUSIONS: Genetic vulnerability involving the SLC6A4 gene is significantly
      associated with both increased depressive symptoms and elevated IL-6 plasma
      levels. Common pathophysiological processes may link depression and inflammation,
      and implicate the serotonin pathway in neural-immune interactions.

PMID- 20031643
TI  - Contribution of genome-wide significant single-nucleotide polymorphisms and
      antiretroviral therapy to dyslipidemia in HIV-infected individuals: a
      longitudinal study.
AB  - BACKGROUND: HIV-infected individuals have an increased risk of myocardial
      infarction. Antiretroviral therapy (ART) is regarded as a major determinant of
      dyslipidemia in HIV-infected individuals. Previous genetic studies have been
      limited by the validity of the single-nucleotide polymorphisms (SNPs)
      interrogated and by cross-sectional design. Recent genome-wide association
      studies have reliably associated common SNPs to dyslipidemia in the general
      population. METHODS AND RESULTS: We validated the contribution of 42 SNPs (33
      identified in genome-wide association studies and 9 previously reported SNPs not
      included in genome-wide association study chips) and of longitudinally measured
      key nongenetic variables (ART, underlying conditions, sex, age, ethnicity, and
      HIV disease parameters) to dyslipidemia in 745 HIV-infected study participants
      (n=34 565 lipid measurements; median follow-up, 7.6 years). The relative impact
      of SNPs and ART to lipid variation in the study population and their cumulative
      influence on sustained dyslipidemia at the level of the individual were
      calculated. SNPs were associated with lipid changes consistent with genome-wide
      association study estimates. SNPs explained up to 7.6% (non-high-density
      lipoprotein cholesterol), 6.2% (high-density lipoprotein cholesterol), and 6.8%
      (triglycerides) of lipid variation; ART explained 3.9% (non-high-density
      lipoprotein cholesterol), 1.5% (high-density lipoprotein cholesterol), and 6.2%
      (triglycerides). An individual with the most dyslipidemic antiretroviral and
      genetic background had an approximately 3- to 5-fold increased risk of sustained
      dyslipidemia compared with an individual with the least dyslipidemic therapy and
      genetic background. CONCLUSIONS: In the HIV-infected population treated with ART,
      the weight of the contribution of common SNPs and ART to dyslipidemia was
      similar. When selecting an ART regimen, genetic information should be considered
      in addition to the dyslipidemic effects of ART agents.

PMID- 20031644
TI  - Genetic ancestry is associated with subclinical cardiovascular disease in African
      Americans and Hispanics from the multi-ethnic study of atherosclerosis.
AB  - BACKGROUND: Differences in cardiovascular disease (CVD) burden exist among
      racial/ethnic groups in the United States, with African-Americans having the
      highest prevalence. Subclinical CVD measures have also been shown to differ by
      race or ethnicity. In the United States, there has been a significant intermixing
      among racial/ethnic groups creating admixed populations. Very little research
      exists on the relationship of genetic ancestry and subclinical CVD measures.
      METHODS AND RESULTS: These associations were investigated in 712 black and 705
      Hispanic participants from the Multi-Ethnic Study of Atherosclerosis candidate
      gene substudy. Individual ancestry was estimated from 199 genetic markers using
      STRUCTURE. Associations of ancestry and coronary artery calcium (CAC) and common
      and internal carotid intima media thickness were evaluated using log-binomial and
      linear regression models. Splines indicated linear associations of ancestry with
      subclinical CVD measures in African-Americans but presence of threshold effects
      in Hispanics. Among African-Americans, each SD increase in European ancestry was
      associated with an 8% (95% CI, 1.02 to 1.15; P=0.01) higher CAC prevalence. Each
      SD increase in European ancestry was also associated with a 2% (95% CI -3.4% to 
      0.5%, P=0.008) lower common carotid intima media thickness in African-Americans.
      Among Hispanics, the highest tertile of European ancestry was associated with a
      34% higher CAC prevalence (P=0.02) when compared with the lowest tertile.
      CONCLUSIONS: The linear association of ancestry and subclinical CVD suggests that
      genetic effects may be important in determining CAC and carotid intima media
      thickness among African-Americans. Our results also suggest that CAC and common
      carotid intima media thickness may be important phenotypes for further study with
      admixture mapping.

PMID- 20031646
TI  - Do hemochromatosis mutations protect against iron-mediated atherogenesis?

PMID- 20031645
TI  - Nutrigenomics in cardiovascular medicine.

PMID- 20031647
TI  - Circulation: cardiovascular interventions: keeping pace with progress.

PMID- 20031648
TI  - Biomarker release after percutaneous coronary intervention: a message from the
      heart.

PMID- 20031649
TI  - Revealing the silver and red lining in drug-eluting stents with angioscopy.

PMID- 20031650
TI  - Significance of periprocedural myonecrosis on outcomes after percutaneous
      coronary intervention: an analysis of preintervention and postintervention
      troponin T levels in 5487 patients.
AB  - BACKGROUND: Myonecrosis after percutaneous coronary intervention (PCI) has been
      correlated with a worse prognosis, but controversy exists about the clinical
      significance and potential mechanisms for the association. The aim of this study
      was to evaluate the relative impact of preprocedural and postprocedural cardiac
      troponin T (cTnT) levels on survival rate after PCI. METHODS AND RESULTS: We
      evaluated 5487 patients from the Mayo Clinic registry who required nonemergency
      PCI, and we examined the relationship between periprocedural cTnT levels, with
      the 99th percentile cutoff value used for normal (<0.01 ng/mL), and outcomes. The
      patients were divided into 3 groups: normal preprocedural and postprocedural cTnT
      levels (no myonecrosis), normal preprocedural but elevated postprocedural cTnT
      levels (PCI-related myonecrosis), and abnormal preprocedural cTnT. The 30-day
      death rates were 0.1%, 0.6%, and 2.3%, respectively, in the 3 groups. In a
      multivariable model, an abnormal pre-PCI cTnT level (hazard ratio 9.66 [2.30
      40.57]; P=0.002), and PCI-related myonecrosis (4.71 [1.02-21.83]; P=0.048) were
      independent predictors of 30-day mortality. Over a median follow-up of 28 months,
      an abnormal pre-PCI cTnT level (hazard ratio 1.79 [1.35-2.39]; P<0.001)
      independently predicted death, but the occurrence of PCI-related myonecrosis did
      not. A postprocedural elevation in creatine kinase MB fraction was not an
      independent predictor of long-term risk of death (0.912 [0.70-1.19]; P=0.5).
      CONCLUSIONS: A preprocedural cTnT level >0.01 is a powerful independent predictor
      of prognosis after PCI and is of greater prognostic significance than the
      postprocedural biomarker levels. PCI-related myonecrosis occurs frequently and
      predicts short-term but not long-term risk of death.

PMID- 20031651
TI  - Lack of association between large angiographic late loss and low risk of in-stent
      thrombus: angioscopic comparison between paclitaxel- and sirolimus-eluting
      stents.
AB  - BACKGROUND: It recently has been hypothesized that a larger late loss may have a
      protective role against stent thrombosis. The relationship between angiographic
      late loss and the presence of thrombus based on angioscopic findings within
      paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) was
      investigated in this study. METHODS AND RESULTS: Prospective 6-month follow-up
      angiographic and angioscopic examinations were performed on 18 patients for PES
      and on 20 patients for SES. Late loss was measured by quantitative coronary
      angiography. Angioscopic neointimal stent coverage (NSC) grade was classified as
      follows: 0=uncovered struts without neointima, 1=visible struts through thin
      neointima, and 2=no visible struts. In each patient, maximum NSC, minimum NSC,
      and the existence of thrombus were evaluated. Late loss and maximum NSC were
      greater in PES than in SES (0.38+/-0.43 versus 0.10+/-0.23 mm; P=0.02 and
      P=0.0004, respectively). Late loss was correlated with maximum NSC (grade 0,
      0.06+/-0.01 mm; grade 1, 0.10+/-0.05 mm; and grade 2, 0.48+/-0.46 mm), whereas
      there was no correlation between late loss and minimum NSC. The prevalence of
      patients with uncovered struts did not differ (44% of PES, 40% of SES; P=0.78).
      In-stent thrombus was found more frequently in PES than in SES (72% versus 40%,
      P=0.046) despite no occurrence of stent thrombosis. Only within PES were thrombi
      found in the segments of NSC grade 2 associated with large late loss.
      CONCLUSIONS: The present study suggests that angiographic large late loss was not
      associated with a low risk of in-stent thrombus.

PMID- 20031652
TI  - High incidence of intramural thrombus after overlapping paclitaxel-eluting stent
      implantation: angioscopic and histopathologic analysis in porcine coronary
      arteries.
AB  - BACKGROUND: Systematic analysis of in vivo angioscopy and postmortem
      histopathology for paclitaxel-eluting stents (PES) has not been previously
      reported. We assessed 1-month angioscopic and histopathologic sequelae of
      overlapping PES in pig coronary arteries. METHODS AND RESULTS: Overlapping PES
      and bare-metal stents (BMS; n=9, one pair per pig) were implanted, and animals
      were euthanized at 1 month. Late lumen loss was reduced in PES compared with BMS
      (0.46+/-0.63 mm versus 1.30+/-0.50 mm; P=0.01). Angioscopically, PES stent struts
      were clearly visible and accompanied by substantial red material indicating mural
      thrombi. In contrast, stent struts and mural thrombi were barely visible in BMS
      (P<0.001 versus PES). Macroscopically, mural thrombi were abundant but
      distributed irregularly throughout the PES, with greater concentration in
      overlapping segments. Only occasional mural thrombi were noted for BMS.
      Microscopically, neointima of BMS was fibrocellular and mature, whereas only a
      thin layer of immature neointima was seen in PES. Neointimal thickness was less
      in PES than BMS (0.11+/-0.07 mm versus 0.33+/-0.12 mm; P=0.018). Additionally,
      extensive para-strut and intramural thrombi, red blood cell debris, and minute
      luminal thrombi were observed in PES. Despite normal angioscopic appearance of
      both proximal and distal nonstented reference segments, endothelium-dependent
      relaxation to substance P was notably diminished (PES, 0+/-7% versus BMS, 10+/
      6%; P=0.007), whereas nitroglycerin response was preserved (PES, 9+/-5% versus
      BMS, 12+/-7%; P=0.34). CONCLUSIONS: In the porcine coronary model, overlapping
      PES is associated with marked intramural thrombi, which was accurately detected
      on angioscopy at 1 month. Moreover, despite normal luminal angioscopic
      appearance, adjacent nonstented reference segments demonstrated impaired
      endothelium-dependent vasoreactivity.

PMID- 20031653
TI  - Validation of the Mayo clinic risk score for in-hospital mortality after
      percutaneous coronary interventions using the national cardiovascular data
      registry.
AB  - BACKGROUND: We sought to validate the recently developed Mayo Clinic Risk Score
      model for in-hospital mortality after percutaneous coronary intervention using an
      independent data set. The Mayo Clinic Risk Score has 7 simple clinical and
      noninvasive variables, available before coronary angiography, for prediction of
      in-hospital mortality. External validation using an independent data set would
      support broader applicability of the model. METHODS AND RESULTS: In-hospital
      mortality after percutaneous coronary intervention on 309 351 patients from the
      National Cardiovascular Data Registry admitted from January 1, 2004, to March,
      30, 2006, was studied. Using the Mayo Clinic Risk Score equation, we assigned
      predicted probabilities of death to each patient. The area under the receiver
      operating characteristics curve was 0.884, indicating excellent discrimination
      overall as well as among subgroups, including gender, diabetes mellitus, renal
      failure, low ejection fraction, different age groups, and multivessel disease.
      Ninety-seven percent of patients undergoing percutaneous coronary intervention
      had a Mayo Clinic Risk Score <10, indicating low to intermediate risk. The Mayo
      Clinic Risk Score model initially slightly underpredicted event rates when
      applied in National Cardiovascular Data Registry data (observed 1.23% versus
      predicted 1.10%), but this underprediction was corrected after recalibration. The
      recalibrated risk score discriminated (c index=0.885) and calibrated well in an
      National Cardiovascular Data Registry validation data set consisting of
      procedures performed between April 1, 2006, and March 30, 2007. CONCLUSIONS:
      Seven variables can be combined into a convenient risk scoring system before
      coronary angiography is performed to predict in-hospital mortality after
      percutaneous coronary intervention. This model may be useful for providing
      patients with individualized, evidence-based estimates of procedural risk as part
      of the informed consent process before percutaneous coronary intervention.

PMID- 20031654
TI  - Drug-eluting stents versus bare-metal stents for off-label indications: a
      propensity score-matched outcome study.
AB  - BACKGROUND: The US Food and Drug Administration recently concluded that data on
      off-label drug-eluting stent (DES) safety are limited. However, in actual
      clinical practice, DES are often used for off-label indications, and
      observational studies demonstrate that complications are higher when compared
      with on-label use. We aimed to determine whether clinical outcomes differ after
      DES and bare-metal stent implantation in a patient cohort defined by DES off
      label indications. METHODS AND RESULTS: We used the national revascularization
      registry in Scotland to identify patients who underwent coronary stenting for an
      off-label indication between January 2003 and September 2005. Individual-level
      linkage to comprehensive national admission and death databases was used to
      ascertain the end points of death, myocardial infarction, and target-vessel
      revascularization. We calculated propensity scores on the basis of clinical,
      demographic, and angiographic variables and matched DES to bare-metal stents on a
      1:1 basis. The final study population consisted of 1642 patients, well matched
      for important covariables at baseline. Event-free survival was calculated over 24
      months with the Kaplan-Meier method. All-cause death was more common after bare
      metal stent implantation during follow-up (7.7% versus 6.6%; hazard ratio 0.63;
      95% confidence interval, 0.40 to 0.99; P=0.04). No difference in the rates of
      myocardial infarction were noted (7.3% versus 7.5%; hazard ratio 1.02; 95%
      confidence interval, 0.69 to 1.54; P=0.92). Target-vessel revascularization was
      reduced in patients treated with DES (13.9% versus 10.7%; hazard ratio 0.67; 95%
      confidence interval, 0.49 to 0.93; P=0.02). CONCLUSIONS: At 24 months, patients
      treated with DES for off-label indications had lower rates of death and target
      vessel revascularization and similar rates of myocardial infarction, as compared
      with patients treated with bare-metal stents.

PMID- 20031655
TI  - Aortic wall injury as a complication of neonatal aortic valvuloplasty: incidence
      and risk factors.
AB  - BACKGROUND: Transcatheter balloon aortic valvuloplasty for critical aortic
      stenosis in neonates is routinely performed without recognized complication.
      Aortic wall injury has rarely been observed after balloon aortic valvuloplasty,
      although the incidence of this complication is unstudied. We reviewed single
      center data to determine the incidence of aortic injury during balloon aortic
      valvuloplasty and to identify risk factors. METHODS AND RESULTS: This
      retrospective study included all patients <2 months of age who underwent balloon
      aortic valvuloplasty at our institution from 1985 to 2007. We defined aortic wall
      injury as an intimal flap, dissection, or vessel rupture as diagnosed by
      angiography, echocardiography, or direct surgical or postmortem inspection.
      Primary imaging data were reviewed, as were all procedural and pathology reports,
      to identify cases of aortic wall injury. Patient and procedural variables were
      analyzed. Of 187 procedures performed, 28 procedures resulted in aortic wall
      injury (15%). Injury was recognized at the time of the procedure in only 16 cases
      (57%). Intimal flaps occurred most commonly in the distal ascending aorta (n=13),
      most often involving the greater curvature. In multivariate analysis, severe
      ventricular dysfunction at the time of the procedure (odds ratio, 2.8; P=0.02),
      greater number of balloon dilation attempts per procedure (odds ratio, 1.5;
      P=0.005), and novice interventional staff (odds ratio, 2.5; P=0.05) were
      associated with aortic injury. Incidence of injury was not different in the
      recent era compared with earlier experience. CONCLUSIONS: Aortic wall injury,
      specifically creation of an intimal flap, is an underrecognized complication of
      neonatal balloon aortic valvuloplasty, occurring in 15% of cases even in the
      recent era. Only severe ventricular dysfunction, greater number of balloon
      dilations, and novice staff were associated with injury. The clinical sequelae of
      aortic wall injury remain incompletely understood.

PMID- 20031656
TI  - Catheter-based treatment of coronary artery disease: past, present, and future.
AB  - September 2007 marked the 30-year anniversary of the first human percutaneous
      coronary intervention, an index event that changed the course of modern-day
      cardiovascular care. Before that first procedure, adult invasive cardiology
      focused on diagnostic angiography as well as hemodynamic assessment of structural
      heart disease. Since that initial procedure, percutaneous coronary intervention
      has become the most frequently performed coronary revascularization procedure
      worldwide. Several factors have been responsible for this dramatic paradigm
      shift, the most prominent being identification of opportunities for technical
      improvement and the application of innovation and investigation in concert with
      colleagues, professional societies, and industry. These approaches will continue
      to be of paramount importance as new technologies are brought to bear on an
      increasingly broader group of patients with cardiovascular disease.

PMID- 20031657
TI  - Anatomy of the aortic valvar complex and its implications for transcatheter
      implantation of the aortic valve.
AB  - The books and articles devoted to the anatomy of the aortic valvar complex are
      numerous. Until now, however, little consideration has been given to
      understanding the anatomy with percutaneous valvar replacement in mind. It is
      axiomatic that knowledge of the anatomy of the valve is fundamental in
      understanding key principles involved in valvar replacement.Such an appreciation
      of the anatomy helps better understand the optimal positioning for the prosthetic
      valve within the root of the aorta with respect to the coronary arteries, mitral
      valve, and the conduction system and may circumvent complications that can arise
      during its implantation [corrected] In this review, therefore, we describe the
      anatomy of the trifoliate aortic valvar complex and its implications for
      percutaneous valvar replacement.

PMID- 20031658
TI  - Unstable angina as a result of coronary-subclavian steal syndrome.

PMID- 20031659
TI  - Giant coronary artery aneurysm: imaging findings before and after treatment with
      a polytetrafluoroethylene-covered stent.

PMID- 20031660
TI  - Primary percutaneous coronary intervention with drug-eluting stents: another
      chapter in the stent controversy.

PMID- 20031661
TI  - Managing patients with intermediate in-stent restenotic lesions: is it "prime
      time" for intravascular ultrasound imaging?

PMID- 20031662
TI  - Carotid stenting for chronic total occlusion of the internal carotid artery:
      dogma debunked?

PMID- 20031663
TI  - Implementation of guidelines for the treatment of acute ST-elevation myocardial
      infarction: the Cologne Infarction Model Registry.
AB  - BACKGROUND: The aim of the Koln (Cologne) Infarction Model is to examine the
      feasibility of obligatory treatment of ST-segment-elevation myocardial infarction
      (STEMI) by first-line percutaneous coronary intervention. METHODS AND RESULTS:
      The study was performed in Cologne with >1 million citizens, 5 coronary
      intervention centers, and 11 primary care hospitals. Twelve-lead ECG was
      available for all emergency medical service (EMS) teams. Partners guaranteed
      direct transfer of STEMI patients to a catheterization laboratory. A total of 519
      patients treated within KIM in 2006 were included in the study. Of these, 24%
      presented at a primary care hospital, 11% presented directly at a coronary
      intervention center, 5% were transferred by EMS to primary care hospitals, and
      60% were directly transferred by EMS to a catheterization laboratory. In 91% of
      cases, the catheterization laboratory was notified of the patient's arrival in
      advance. False-positive ECG diagnosis of STEMI by EMS accounted for 6%. Median
      treatment times were as follows: from the start of symptoms to first medical
      contact, 120 minutes; phone to balloon, 70 minutes; and door to balloon, 49
      minutes. Of all patients, 93% underwent angiography; 409 patients were treated by
      coronary intervention, and 24 underwent emergency coronary artery bypass graft.
      Thrombolysis in Myocardial Infarction grade 3 flow was obtained in 89%. In the
      hospitals, deaths and new myocardial infarctions were observed in 12.1% and in
      1.9% of all patients, respectively. CONCLUSIONS: The Cologne Infarction Model
      provides evidence for the feasibility of obligatory treatment of STEMI by primary
      coronary intervention in a metropolitan setting. Acceptance of treatment pathways
      allowed nearly all STEMI patients to undergo coronary angiography. ECG competence
      of EMS was excellent. Treatment times were within postulated limits. Results,
      including mortality, were within a high quality range.

PMID- 20031664
TI  - Primary percutaneous coronary intervention for acute myocardial infarction: long
      term outcome after bare metal and drug-eluting stent implantation.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PPCI) for ST-elevation
      myocardial infarction with bare metal stents (BMS) is well established, while
      randomized trials suggest equivalent safety and reduced repeat revascularization
      with drug-eluting stents (DES) in this setting. However, long-term data on DES in
      PPCI is lacking, especially in those ineligible for inclusion in randomized
      trials. Our aim was to investigate the long-term outcomes of unselected patients
      undergoing PPCI with BMS and DES. METHODS AND RESULTS: We analyzed all patients
      (n=1738) undergoing PPCI for a de novo lesion in our institution from 2000 to
      2005. Patients from 3 sequential consecutive cohorts of BMS (n=531), sirolimus
      eluting (SES, n=185) or paclitaxel-eluting stents (PES, n=1022) were included.
      The median duration of follow-up was 1185 days (interquartile range, 746 to
      1675). There were no differences in all-cause mortality or repeat
      revascularization between DES and BMS, although there was a nonsignificant trend
      toward improved survival with SES compared with both BMS (propensity score
      adjusted hazard ratio, 0.63; [95%CI, 0.33 to 1.18]) and PES (hazard ratio, 0.71;
      [95% CI, 0.40 to 1.26]). SES were associated with lower rates of the composite
      end point of all-cause death, nonfatal myocardial infarction, or target vessel
      revascularization (hazard ratio, 0.62; 95%CI, 0.40 to 0.96) when compared with
      PES. Very late stent thrombosis only occurred in the DES groups. CONCLUSIONS:
      Although DES are not associated with an increase in adverse events compared with
      BMS when used for PPCI, neither DES reduced repeat revascularizations.
      Appropriately powered randomized trials with hard clinical end points and an "all
      comer" design are required to further assess the benefit of DES in PPCI.

PMID- 20031665
TI  - Impact of in-stent minimal lumen area at 9 months poststent implantation on 3
      year target lesion revascularization-free survival: a serial intravascular
      ultrasound analysis from the TAXUS IV, V, and VI trials.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) is used to assess intermediate
      lesions in native coronary arteries; minimum lumen area (MLA) <4.0 mm(2) is
      accepted as a cutoff for a significant stenosis. We evaluated the IVUS in-stent
      MLA at 9-month follow-up that best predicted subsequent target lesion
      revascularization (TLR)-free survival in patients from the TAXUS IV, V, and VI
      studies. METHODS AND RESULTS: In the combined TAXUS IV, V, and VI randomized
      trials, 9-month IVUS was available in 635 patients (331 treated with paclitaxel
      eluting stents [PES] and 304 treated with bare-metal stents [BMS]) who did not
      require TLR in the first 9 months postintervention and who were followed for 3
      years. The in-stent MLA that best predicted 3-year TLR-free survival was
      determined. At 9-months follow-up, IVUS-measured in-stent MLA was 5.7 + or -2.3
      mm(2) in the PES group and 4.8 + or - 2.3 mm(2) in the BMS group. Between 9
      months and 3 years, TLR was required in 4.9% of patients who were treated with
      PES and 6.7% of patients who were treated with BMS. Multivariate analysis
      identified MLA at 9 months as a significant predictor of late TLR (hazard ratio,
      0.63 [0.43-0.93]; P = 0.02). The ability of MLA to predict late TLR was further
      assessed using receiver operating characteristic analysis. MLA was found to be an
      acceptable discriminator for both PES (c = 0.7448) and BMS (c = 0.7329). Finally,
      the optimal thresholds of MLA that best predicted subsequent TLR-free survival
      were determined to be 4.2 mm(2) for PES and 4.0 mm(2) for BMS. CONCLUSIONS: In
      the combined IVUS analysis of TAXUS IV, V, and VI, patients who did not require
      TLR within the first 9 months had a high subsequent TLR-free survival rate
      whether treated with PES or BMS. MLA measured by IVUS at 9 months predicted
      subsequent TLR with a cutoff similar to intermediate, de novo lesions in native
      coronary arteries.

PMID- 20031666
TI  - Procedural safety and potential vascular complication of endovascular
      recanalization for chronic cervical internal carotid artery occlusion.
AB  - BACKGROUND: Patients with chronic cervical internal carotid artery occlusion
      (ICAO) and cerebral ischemia may benefit from revascularization. The feasibility
      of endovascular recanalization for chronic ICAO has been reported recently, but
      its safety is still unproven. We report the follow-up results of 54 chronic ICAO
      patients who underwent endovascular recanalization, focusing on potential
      vascular complications and corresponding management. METHODS AND RESULTS:
      Endovascular recanalization for chronic ICAO was attempted in 54 consecutive
      patients (48 men; 69.2 + or - 9.8 years old) with either recurrent neurological
      deficit or objective ipsilateral hemisphere ischemia. Mean duration from
      occlusion documentation to the procedure was 237 + or - 327 days (range, 56 to
      1424 days). Adverse events while in the hospital and during the 3-month follow-up
      were recorded. Successful recanalization was achieved in 35 of 54 patients (65%).
      Three-month cumulative stroke and death rate was 4% (2 of 54), including 1 in
      hospital fatal nonipsilateral stroke and 1 in-hospital minor ipsilateral stroke
      secondary to systemic hypotension. Vascular complications developed in 3 of 54
      patients (6%), including 1 late pseudoaneurysm formation 3 months after
      recanalization, 1 immediate carotid-cavernous fistula after recanalization, and 1
      minor extravasation at carotid bifurcation after failed recanalization. However,
      no clinical sequela was noted with close follow-up and adequate management.
      CONCLUSIONS: Certain immediate or delayed vascular complications may develop
      during or after the endovascular recanalization for chronic ICAO. Although
      periprocedural death and stroke rate is limited in our study, further study
      combining neuroimaging tools and cognitive function evaluation is mandatory to
      assess its utility and appropriateness in patients with chronic ICAO.

PMID- 20031668
TI  - Trans-coronary-venous interventions.
AB  - The coronary venous system is routinely targeted during electrophysiological
      measurements or cardiac resynchronization therapy. However, several novel
      interventional techniques require coronary venous catheterization and
      visualization as well as transvenous delivery of devices and/or therapeutic
      agents. Recent reports suggest the possibility of a transvenous approach for the
      interventional treatment of refractory angina and mitral valve regurgitation. In
      addition, the coronary venous system has been used as a route for the delivery of
      stem cells in patients with left ventricular dysfunction due to ischemic heart
      disease. We review the potential value of using a coronary venous approach in
      association with recent therapeutic developments in the interventional treatment
      of structural and ischemic heart disease. We will also discuss techniques related
      to coronary venous catheterization.

PMID- 20031667
TI  - Retrograde transarterial implantation of a nonmetallic aortic valve prosthesis in
      high-surgical-risk patients with severe aortic stenosis: a first-in-man
      feasibility and safety study.
AB  - BACKGROUND: To assess the feasibility and safety of retrograde transarterial
      implantation of a novel nonmetallic aortic valve prosthesis (Direct Flow Medical
      Inc, Santa Rosa, Calif), a prospective single-center study was performed in
      patients with severe aortic stenosis at high risk for open-heart surgery. METHODS
      AND RESULTS: Fifteen patients (intention-to-treat cohort) with an aortic valve
      area < or = 0.8 cm(2), a > or = 35-mm Hg mean transvalvular pressure gradient,
      and a logistic EuroSCORE > or = 20% were enrolled. Percutaneous aortic valve
      replacement was performed with the patient under general anesthesia. Hemodynamic
      parameters were assessed before and after implantation by transesophageal
      echocardiography. Clinical follow-up and transthoracic echocardiographic
      assessment were obtained at 30 days. Procedural success was achieved in 12
      patients (80%). Surgical conversion became necessary at day 2 in 1 patient; 11
      patients (73%) were discharged with a permanent implant. In these patients,
      implantation resulted acutely in a significant increase in aortic valve area
      (median, 1.64 [interquartile range, 1.27 to 1.74] versus 0.60 [0.46 to 0.69]
      cm(2); P = 0.0033) and a concomitant reduction in the mean pressure gradient
      (14.0 [13.2 to 16.5] versus 54.0 [43.2 to 59.8] mm Hg; P = 0.0033). At 30 days, 1
      cardiac death (6.7%; 95% CI, 0.2% to 32.0%) and 1 major stroke were observed. The
      10 surviving patients with a permanent implant showed marked hemodynamic and
      clinical improvement at this time point. CONCLUSIONS: In this small series of
      patients, percutaneous implantation of the Direct Flow Medical aortic valve
      prosthesis in high-surgical-risk patients was feasible and associated with a
      reasonably low safety profile.

PMID- 20031669
TI  - Drug-eluting stents in preclinical studies: updated consensus recommendations for
      preclinical evaluation.
AB  - Coronary drug-eluting stents are commonplace in clinical practice with acceptable
      safety and efficacy. Preclinical evaluation of novel drug-eluting stent
      technologies has great importance for understanding safety and possibly efficacy
      of these technologies, and well-defined preclinical testing methods clearly
      benefit multiple communities within the developmental, testing, and clinical
      evaluation chain. An earlier consensus publication enjoyed widespread adoption
      but is in need of updating. This publication is an update, presenting an
      integrated view for testing drug-eluting technologies in preclinical models,
      including novel devices such as bioabsorbable coatings, totally bioabsorbable
      stents, bifurcation stents, and stent-free balloon-based drug delivery. This
      consensus document was produced by preclinical and translational scientists and
      investigators engaged in interventional technology community. The United States
      Food and Drug Administration (USFDA) recently issued a Draft Guidance for
      Industry Document for Drug-Eluting Stents. This expert consensus document is
      consistent with the Food and Drug Administration guidance. The dynamic nature of
      this field mandates future modifications and additions that will be added over
      time.

PMID- 20031670
TI  - Major polymer damage of drug-eluting stents.

PMID- 20031671
TI  - Ingrowths of a percutaneously implanted aortic valve prosthesis (corevalve) in a
      patient with severe aortic stenosis.

PMID- 20031672
TI  - Transcatheter aortic valve implantation: past, present, and future.

PMID- 20031673
TI  - Drug-eluting or bare-metal stents for ST elevation myocardial infarction can
      observational data balance the risk benefit equation?

PMID- 20031674
TI  - Change we can believe in: the hyper-evolution of percutaneous coronary
      intervention for unprotected left main disease with drug-eluting stents.

PMID- 20031675
TI  - Progress and current status of percutaneous aortic valve replacement: results of
      three device generations of the CoreValve Revalving system.
AB  - BACKGROUND: Percutaneous aortic valve replacement is a new emerging technology
      for interventional treatment of severe aortic valve stenosis in surgical high
      risk patients. This study was intended to provide a summary of the development
      and current safety and efficacy status of the self-expanding CoreValve Revalving
      prosthesis. METHOD AND RESULTS: Between 2005 and 2008, we have enrolled 136
      consecutive patients with percutaneous aortic valve replacement using the
      CoreValve prosthesis. In this prospective nonrandomized, single-center trial, we
      analyzed procedural outcome, complications and clinical status up to 1 year.
      First, second, and third generation of the CoreValve prosthesis were implanted in
      10, 24, and 102 consecutive high-risk patients (logistic EuroScore: 23.1+/-15.0%)
      with severe symptomatic aortic valve stenosis. Mean transvalvular pressure
      gradient was 41.5+/-16.7 mm Hg. The procedural success rate increased from
      generation 1/2 to 3 from 70.0%/70.8% to 91.2% (P=0.003). The 30-day combined rate
      of death/stroke/myocardial infarction was 40.0%/20.8%/14.7% (P=0.11) for
      generation 1, 2, and 3, with no procedural death in generation 3. Pressure
      gradients improved significantly with a final mean gradient of 8.1+/-3.8 mm Hg.
      Overall functional status assessed by New York Heart Association class improved
      from 3.3+/-0.5 (pre) to 1.7+/-0.7 (post) (P<0.001) and remained stable in the
      follow-up. CONCLUSIONS: In experienced hands, percutaneous aortic valve
      replacement with the CoreValve system for selected patients with severe aortic
      valve stenosis has a high acute success rate associated with a low periprocedural
      mortality/stroke rate as well as remarkable clinical and hemodynamic
      improvements, which persist over time. Additional studies are now required to
      confirm these findings, particularly head-to-head comparisons with surgical valve
      replacement in different risk populations.

PMID- 20031676
TI  - Clinical outcome after primary percutaneous coronary intervention with drug
      eluting and bare metal stents in patients with ST-segment elevation myocardial
      infarction.
AB  - BACKGROUND: The use of drug-eluting stents (DESs) versus bare metal stents (BMSs)
      in primary percutaneous coronary intervention (PCI) for ST-segment elevation
      myocardial infarction is a matter of debate. Therefore, we examined the risk of
      target lesion revascularization (TLR), stent thrombosis, myocardial infarction,
      and death after the implantation of DES or BMS in primary PCI patients in Western
      Denmark. METHODS AND RESULTS: A total of 3756 consecutive patients with ST
      segment elevation myocardial infarction treated with primary PCI and stent
      implantation, recorded in the Western Denmark Heart Registry from January 2002
      through June 2005, were followed up for 2 years. We used Cox regression analysis
      to control for confounding. The 2-year incidence of definite stent thrombosis was
      1.9% in the DES group and 1.1% in the BMS group (adjusted relative risk
      [RR]=1.53; 95% CI=0.84 to 2.78; P=0.17). Very late definite stent thrombosis (>
      or =12 months) was seen in 0.4% in the DES group and 0.06% in the BMS group
      (adjusted RR=6.74; 95% CI=1.23 to 37.00; P=0.03). The 2-year incidence of
      myocardial infarction was similar in the 2 groups, 5.2% in the DES group versus
      6.3% in the BMS group (P=0.28; adjusted RR=1.13; 95% CI=0.81 to 1.59; P=0.47).
      All-cause 2-year mortality was 7.8% in the DES group and 11.4% in BMS group
      (P<0.004; adjusted RR=0.79; 95% CI=0.60 to 1.04; P=0.09). The 2-year incidence of
      target lesion revascularization was 7.2% in the DES group and 8.7% in the BMS
      group (P=0.09; adjusted RR=0.70; 95% CI=0.52 to 0.92; P=0.012). CONCLUSIONS: In
      ST-segment elevation myocardial infarction patients treated with primary PCI,
      target lesion revascularization was reduced by 30% in patients treated with a
      DES. The risk of very late definite stent thrombosis was low but increased in
      patients treated with DES. DES was not associated with increased risk of
      myocardial infarction or death, when compared with BMS.

PMID- 20031677
TI  - Impact of bifurcation technique on 2-year clinical outcomes in 773 patients with
      distal unprotected left main coronary artery stenosis treated with drug-eluting
      stents.
AB  - BACKGROUND: Distal unprotected left main coronary artery (ULMCA) stenosis
      represents a technical challenge for interventional cardiologists. In this study,
      we compared 2-year clinical outcomes of different stenting strategies in patients
      with distal ULMCA stenosis treated with drug-eluting stents. METHODS AND RESULTS:
      The survey promoted by the Italian Society of Invasive Cardiology on ULMCA
      stenosis was an observational study on patients with ULMCA stenosis treated with
      percutaneous coronary intervention. In this study, we selected patients with
      distal ULMCA stenosis treated with drug-eluting stents. Seven hundred seventy
      three patients were eligible for this study: 456 were treated with 1 stent (group
      1) and 317 with 2 stents (group 2). The primary end point of the study was the
      incidence of major adverse cardiac events (MACEs), defined as the occurrence of
      mortality, myocardial infarction, and target lesion revascularization. During a 2
      year follow-up, risk-adjusted survival free from MACE was significantly higher in
      patients in group 1 than in patients in group 2. The propensity-adjusted hazard
      ratio for the risk of 2-year MACE in patients in group 1 versus group 2 was 0.53
      (95% CI, 0.37 to 0.76). The propensity-adjusted hazard ratio for the risk of 2
      year cardiac mortality and myocardial infarction in patients in group 1 versus
      group 2 was 0.38 (95% CI, 0.17 to 0.85). CONCLUSIONS: Compared with the 2-stent
      technique, the 1-stent technique is associated with a better 2-year MACE-free
      survival. The stenting strategy is a prognostic factor that should be taken into
      account when deciding the optimal revascularization treatment.

PMID- 20031678
TI  - Interference of drug-eluting stents with endothelium-dependent coronary
      vasomotion: evidence for device-specific responses.
AB  - BACKGROUND: There is evidence that endothelial coverage of drug-eluting stents
      might be delayed or absent, a risk factor for late thrombotic events. We studied
      the effects of different drug-polymer-device iterations on endothelium-dependent
      coronary vasomotion. Systemic markers of endothelial inflammation were correlated
      with coronary vasomotor changes. METHODS AND RESULTS: Patients with paclitaxel
      eluting stents (n=11), sirolimus-eluting stents (n=21), biolimus A9-eluting
      stents (n=28), zotarolimus-eluting stents (n=10), and bare-metal stents (n=13)
      were studied 10, 9, 9, 9, and 12 months after implantation, respectively.
      Endothelium-dependent coronary vasomotion was tested proximally and distally to
      the stent and at a reference vessel segment during atrial pacing at increasing
      heart rates by quantitative coronary angiography. Indexes of platelet-monocyte
      binding and other biomarkers were studied in a subgroup of 19 patients. The
      baseline characteristics and hemodynamics of the patients in the different stent
      groups were comparable. Significant differences were observed across the 5 stent
      groups, concerning the vasomotion of segments proximal (P=0.006) and distal
      (P=0.003) to the stent. Normal vasomotion (vasodilatation) was maintained in the
      biolimus A9-eluting stent, zotarolimus-eluting stent, and bare-metal stent
      groups, whereas vasoconstriction was observed in the sirolimus-eluting stent and
      paclitaxel-eluting stent groups. Platelet-monocyte binding in whole blood showed
      a significant inverse correlation with vasomotion in reference but not in
      segments adjacent to the stent (r=-0.57; P=0.01). CONCLUSIONS: Paclitaxel-eluting
      stents and sirolimus-eluting stents seem to cause endothelial dysfunction of the
      implanted vessel, whereas biolimus A9-eluting stents and zotarolimus-eluting
      stents behave more closely to bare-metal stents, with preserved endothelial
      vasomotor response. Coronary vasoconstriction was not associated with detectable
      systemic endothelial activation.

PMID- 20031679
TI  - Poor 1-year outcomes after percutaneous coronary interventions in systemic lupus
      erythematosus: report from the National Heart, Lung, and Blood Institute Dynamic
      Registry.
AB  - BACKGROUND: Women with systemic lupus erythematosus (SLE) have premature and
      accelerated atherosclerosis. Although percutaneous coronary intervention (PCI) is
      used frequently to treat coronary artery disease in SLE, little is known
      regarding PCI outcomes immediately after PCI and after discharge. METHODS AND
      RESULTS: Baseline demographic, procedure-related, and adverse outcome data on
      consecutive patients undergoing PCI during 5 recruitment "waves" of the National
      Heart, Lung, and Blood Institute Dynamic Registry across 23 clinical centers were
      collected. SLE patients (n=28) were compared with non-SLE patients (n=3385). SLE
      patients were younger and more often female in comparison with non-SLE patients
      undergoing PCI. SLE patients were less likely than non-SLE patients to have
      hyperlipidemia but had a similar prevalence of hypertension, diabetes mellitus,
      and tobacco use. The prevalence of multivessel disease was similar between
      groups. Initial intervention success (by angiographic definition) was not
      significantly different between groups. At 1 year, SLE patients were more likely
      to experience a myocardial infarction (15.6% versus 4.8%, P=0.01) and more often
      required repeat PCI (31.3% versus 11.8%, P=0.009) than non-SLE patients, even
      after adjustment for important covariates. CONCLUSIONS: SLE patients had
      significantly worse cardiovascular outcomes at 1 year than non-SLE patients. Even
      considering the small number of SLE patients, these differences were striking.
      Further study is warranted to explore other factors potentially accounting for
      this disparity, including SLE disease activity and duration, presence of
      hypercoagulable state, and immunosuppressive therapy.

PMID- 20031680
TI  - Inhibition of apoptosis through localized delivery of rapamycin-loaded
      nanoparticles prevented neointimal hyperplasia and reendothelialized injured
      artery.
AB  - BACKGROUND: A significant fraction of vascular smooth muscle cells (VSMCs)
      undergo rapid apoptosis after balloon angioplasty. In this study, we tested the
      hypothesis that protecting VSMCs from undergoing apoptosis prevents the cascade
      of events that lead to intimal hyperplasia. METHODS AND RESULTS: Rapamycin-loaded
      gel-like nanoparticles (mean diameter, 54+/-5 nm) were infused locally in a rat
      carotid artery model of vascular injury. The drug has both antiapoptotic and
      antiproliferative effects on VSMCs and hence was selected for the current study.
      Localized delivery of nanoparticles sustained the drug level in the target artery
      for >2 weeks; demonstrated significant inhibition of hyperplasia (intima/media
      ratio, 1.5+/-0.02 versus 2.7+/-0.6; P<0.01); and most importantly, re
      endothelialized the injured artery (endothelium coverage: treated 82% versus
      control 28%). We also demonstrated inhibition of activation of caspase-3/7
      enzymes in the treated artery, preventing VSMCs from undergoing apoptosis and
      subsequent infiltration of macrophages. CONCLUSIONS: It may be postulated that
      the localized delivery of rapamycin inhibited apoptosis of VSMCs, minimizing the
      inflammatory response to the injury and, thus, creating conditions conducive to
      vascular repair (re-endothelialization). Unlike stenting, which can lead to
      thrombosis and increased risk for in-stent restenosis, our approach could
      eliminate or minimize long-term complications because the injured artery
      undergoes a natural process of re-endothelialization.

PMID- 20031681
TI  - Should dual antiplatelet therapy after drug-eluting stents be continued for more
      than 1 year?: Dual antiplatelet therapy after drug-eluting stents should be
      continued for more than one year and preferably indefinitely.

PMID- 20031682
TI  - Should dual antiplatelet therapy after drug-eluting stents be continued for more
      than 1 year?: Dual antiplatelet therapy after drug-eluting stents should not be
      continued for more than 1 year and preferably indefinitely.

PMID- 20031683
TI  - Apical aortic valve implantation in a patient with a mechanical valve prosthesis
      in mitral position.

PMID- 20031685
TI  - The first generation of angioplasty.

PMID- 20031686
TI  - Advancing biomarker science in the 21st century.

PMID- 20031687
TI  - Twenty-year evolution of percutaneous coronary intervention and its impact on
      clinical outcomes: a report from the National Heart, Lung, and Blood Institute
      sponsored, multicenter 1985-1986 PTCA and 1997-2006 Dynamic Registries.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) has undergone rapid
      progress, both in technology and adjunct therapy. However, documentation of long
      term temporal trends in relation to contemporary practice is lacking. METHODS AND
      RESULTS: We analyzed PCI use and outcomes in 8976 consecutive patients in the
      multicenter, National Heart, Lung, and Blood Institute-sponsored 1985-1986
      percutaneous transluminal coronary angioplasty (PTCA) and 1997-2006 Dynamic
      Registries waves (wave 1: 1997-1998, bare-metal stents; wave 2: 1999, uniform use
      of stents; wave 3: 2001-2002, brachytherapy; waves 4 and 5: 2004-2006, drug
      eluting stents). Patients undergoing PCI in the recent waves were older and more
      often reported comorbidities than those in the balloon era. PCI was more often
      performed for acute coronary syndromes and, in spite of the greater disease
      burden, was more often selective. Procedural success was achieved and maintained
      more often in the stent era. Significant reductions were observed in in-hospital
      rates (%) of myocardial infarction (PTCA Registry: 4.9; wave 1, 2.7; wave 2, 2.8;
      wave 3, 1.9; wave 4, 2.6; wave 5, 2; P(trend)<0.001) and emergency coronary
      artery bypass surgery (PTCA Registry: 3.7; wave 1, 0.4; wave 2, 0.4; wave 3, 0.3;
      wave 4, 0.4; wave 5, 0; P(trend)<0.001). Compared with the PTCA Registry, risk
      for repeat revascularization (31 to 365 days after index PCI) was significantly
      lower in the dynamic waves (adjusted hazard ratio: wave 1, 0.72; wave 2, 0.51;
      wave 3, 0.51; wave 4, 0.30; wave 5, 0.36; P<0.05 for all). CONCLUSIONS:
      Percutaneous interventions, in the last 2 decades, have evolved to include more
      urgent, comorbid cases, despite achieving high success rates with significantly
      reduced need for repeat revascularization.

PMID- 20031688
TI  - Vitronectin concentrations predict risk in patients undergoing coronary stenting.
AB  - BACKGROUND: Vitronectin is a multifunctional protein with a multiple binding
      domain that interacts with a variety of plasma and cell proteins. Vitronectin
      binds multiple ligands, including the soluble vitronectin receptor. Abciximab
      binds equally well to soluble vitronectin receptor and glycoprotein IIb/IIIa,
      because both share the beta(3) subunit. We tested whether vitronectin
      concentrations correlate with adverse outcomes in acute coronary syndrome
      patients. METHODS AND RESULTS: Baseline serum samples (n=233) from a randomized,
      placebo-controlled trial of abciximab plus stenting (Evaluation of Platelet
      IIb/IIIa Inhibitor for Stenting EPISTENT) were retrospectively analyzed. We
      stratified vitronectin concentrations into the 3 lower quartiles (n=178; <49.7
      microg/mL) versus the fourth upper quartile (n=55; >or=49.7 microg/mL). The end
      point was a major adverse cardiovascular event defined as death, myocardial
      infarction or urgent revascularization at 30 days and 6 months. A higher
      proportion of patients with baseline vitronectin >or=49.7 microg/mL had major
      adverse cardiovascular event than patients with baseline vitronectin <49.7
      microg/mL at 30 days (18.2% versus 5.6%; P=0.01) and 6 months (20.0% versus 6.2%;
      P=0.006). When baseline variables not predictive of major adverse cardiovascular
      event (eg, troponin positive, history of congestive heart failure, diabetes,
      history of hypertension, smoking status) were excluded from the multivariate
      model, only baseline vitronectin >or=49.7 microg/mL (at 30 days: OR, 3.23; 95%
      CI, 1.23, 8.49; at 6 months: OR, 3.36; 95% CI, 1.33, 8.52) and history of
      myocardial infarction (at 30 days: OR, 5.02; 95% CI, 1.41, 17.9; at 6 months: OR,
      3.99; 95% CI, 1.28, 12.43) remained. No interaction occurred between abciximab
      and vitronectin. CONCLUSIONS: Our findings indicate that vitronectin may be an
      independent predictor of adverse cardiovascular outcomes following acute
      stenting.

PMID- 20031689
TI  - Trends in the association between age and in-hospital mortality after
      percutaneous coronary intervention: National Cardiovascular Data Registry
      experience.
AB  - BACKGROUND: Temporal trends and contemporary data characterizing the impact of
      patient age on in-hospital outcomes of percutaneous coronary interventions are
      lacking. We sought to determine the importance of age by assessing the in
      hospital mortality of stratified age groups in the National Cardiovascular Data
      Registry. METHODS AND RESULTS: In-hospital mortality after percutaneous coronary
      intervention on 1 410 069 patients was age stratified into 4 groups-group 1 (age
      <40, n=25 679), group 2 (40 to 59, n=496 204), group 3 (60 to 79, n=732 574), and
      group 4 (>or=80, n=155 612)-admitted from January 1, 2001, to December 31, 2006.
      Overall in-hospital mortality was 1.22%; in-hospital mortality was 0.60%, 0.59%,
      1.26%, and 3.16% in groups 1 to 4, respectively, P<0.0001. Overall temporal
      improvement per calendar year in the adjusted in-hospital mortality after
      percutaneous coronary intervention was noted in most groups; however, this
      finding was significant only in the 2 older age groups, group 3 (odds ratio,
      0.94; 95% CI, 0.92 to 0.96) and group 4 (odds ratio, 0.95; 95% CI, 0.92 to 0.97).
      The absolute mortality reduction was greatest in the most elderly group, those
      over the age of 80 years. CONCLUSIONS: In-hospital mortality after percutaneous
      coronary intervention has fallen for all age groups over the past 6 years.
      However, the largest absolute reduction was seen among patients 80 years of age
      or older.

PMID- 20031691
TI  - Effect of length and diameter of drug-eluting stents versus bare-metal stents on
      late outcomes.
AB  - BACKGROUND: The risk of restenosis and other adverse cardiac events with bare
      metal stents (BMS) is increased with smaller stent diameters and longer stent
      lengths. Drug-eluting stents (DES) may reduce this effect in select patients;
      however, whether this benefit occurs in high-risk lesions and patients in routine
      practice is not clear. METHODS AND RESULTS: Clinical outcomes (target-vessel
      revascularization [TVR], stent thrombosis, nonfatal myocardial infarction [MI],
      and cardiac death) at 2 years stratified by stented length and diameter were
      compared in 949 consecutive patients who received BMS and 1236 consecutive and
      comparable patients who received DES for single lesions. The longest tertile of
      BMS (>23 mm) was associated with increased hazard of TVR, ST, and nonfatal MI or
      death compared with shorter tertiles of BMS, which was abolished by DES. DES
      compared with BMS was independently associated with a lower hazard of TVR (HR,
      0.34 [0.20 to 0.58]) and nonfatal MI or death (HR, 0.60 [0.39 to 0.92]) in the
      longest length tertile (>23 mm). No clear association of stented tertile diameter
      and clinical outcomes for either stent type was observed. However, DES compared
      with BMS was independently associated with a lower hazard of TVR for all diameter
      tertiles, and a lower hazard of nonfatal MI or death (0.66 [0.44 to 0.99]) in the
      largest diameter tertile (>3.4 mm). CONCLUSIONS: Independent of adverse patient
      and lesion characteristics, DES demonstrated significantly lower hazard of TVR
      and nonfatal MI or death at 2 years compared with BMS within the longest stented
      lengths (>23 mm) and largest diameters (>3.4 mm).

PMID- 20031690
TI  - Randomized comparison of coronary bifurcation stenting with the crush versus the
      culotte technique using sirolimus eluting stents: the Nordic stent technique
      study.
AB  - BACKGROUND: In a number of coronary bifurcation lesions, both the main vessel and
      the side branch need stent coverage. Using sirolimus eluting stents, we compared
      2 dedicated bifurcation stent techniques, the crush and the culotte techniques in
      a randomized trial with separate clinical and angiographic end-points. METHODS
      AND RESULTS: A total of 424 patients with a bifurcation lesion were randomized to
      crush (n=209) and culotte (n=215) stenting. The primary end point was major
      adverse cardiac events; cardiac death, myocardial infarction, target vessel
      revascularization, or stent thrombosis after 6 months. At 6 months there were no
      significant differences in major adverse cardiac event rates between the groups;
      crush 4.3%, culotte 3.7% (P=0.87). Procedure and fluoroscopy times and contrast
      volumes were similar in the 2 groups. The rates of procedure-related increase in
      biomarkers of myocardial injury were 15.5% in crush versus 8.8% in culotte group
      (P=0.08). A total of 324 patients had a quantitative coronary assessment at the
      index procedure and after 8 months. The angiographic end-points of in-segment and
      in-stent restenosis of main vessel and/or side branch after 8 months were found
      in 12.1% versus 6.6% (P=0.10) and in 10.5% versus 4.5% (P=0.046) in the crush and
      culotte groups, respectively. CONCLUSIONS: Both the crush and the culotte
      bifurcation stenting techniques were associated with similar and excellent
      clinical and angiographic results. Angiographically, there was a trend toward
      less in-segment restenosis and significantly reduced in-stent restenosis
      following culotte stenting.

PMID- 20031692
TI  - Stent parameters predict major adverse clinical events and the response to
      platelet glycoprotein IIb/IIIa blockade: findings of the ESPRIT trial.
AB  - BACKGROUND: Only limited data describe relationships between stent parameters
      (length and diameter), adverse events after percutaneous coronary intervention,
      and effects of platelet glycoprotein IIb/IIIa blockade by stent parameters.
      METHODS AND RESULTS: In this post hoc analysis of the 1983 patients receiving a
      stent in the Enhanced Suppression of the Platelet Glycoprotein IIb/IIIa Receptor
      with Integrilin Therapy randomized percutaneous coronary intervention trial of
      eptifibatide versus placebo, rates of the major adverse cardiac event (MACE) end
      point (death, myocardial infarction, urgent target-vessel revascularization, or
      thrombotic bailout) at 48 hours and 1 year were correlated with stent parameters
      and then analyzed by randomization to eptifibatide versus placebo. In the placebo
      group, MACE increased with number of stents implanted, total stent length (by
      quartiles of <15, 15 to <18, 18 to <30, and >or=30 mm), and total stented vessel
      area (by quartiles of area <141, 141 to <188, 188 to <292, and >or=292 mm(2)). By
      stent parameters, MACE at 48 hours was reduced in the eptifibatide group at stent
      lengths of 18 to <30 mm (odds ratio [OR], 0.55; 95% CI, 0.32 to 0.94; P=0.030)
      and >or=30 mm (OR, 0.43; 95% CI, 0.25 to 0.75; P=0.003), stent diameters of >2.5
      to <3.5 mm (OR, 0.56; 95% CI, 0.39 to 0.82; P=0.002), and with 2 stents implanted
      (OR, 0.39; 95% CI, 0.22 to 0.69; P=0.001). In the placebo group, near-linear
      relationships were observed between both increasing stent length and increasing
      stented vessel area and MACE at 48 hours and 1 year (all, P<0.001); these
      gradients were flattened in the eptifibatide group (P=0.005 for stent length).
      CONCLUSIONS: Stent parameters predict MACE after percutaneous coronary
      intervention. Glycoprotein IIb/IIIa blockade mitigates much of the hazard of
      increasing procedural complexity.

PMID- 20031693
TI  - Ultra-high-pressure balloon angioplasty for treatment of resistant stenoses
      within or adjacent to previously implanted pulmonary arterial stents.
AB  - BACKGROUND: Stents are essential tools in the management of pulmonary arterial
      (PA) stenosis in patients with congenital heart disease. Although stents can
      usually be reexpanded as children grow, resistant in-stent or peri-stent
      obstruction can complicate the management of PA stents. Angioplasty with ultra
      high-pressure (UHP) balloons may facilitate successful treatment of stent
      associated PA stenoses that are resistant to high-pressure dilation. METHODS AND
      RESULTS: We reviewed patients who underwent UHP angioplasty of in-stent or peri
      stent PA stenoses that were resistant to high-pressure redilation. A resistant
      stenosis was defined as a residual balloon waist during high-pressure redilation
      of the stent, along with a pressure gradient and/or angiographic stenosis. Thirty
      four lesions in 29 patients, including 8 with multiple concentric, overlapping,
      or adjacent stents, were included. The median age at UHP angioplasty was 9 years,
      and a median of 4 years had elapsed since unsuccessful high-pressure angioplasty.
      Thirty-one of the 34 (91% [81% to 100%]) UHP angioplasty procedures were
      successful in relieving the resistant stenosis. Balloon:waist diameter ratios
      were conservative (median 1.26), reflecting the ability of UHP balloons to
      "fracture" nearly all obstructions. After UHP dilation, lesion diameter increased
      by a median of 3.1 mm (36%), significantly more than after previous high-pressure
      dilation (1.3 mm, 19%; P<0.001). In 5 lesions, UHP angioplasty fractured the
      stent, allowing further vessel expansion. There were no vascular or other
      complications. CONCLUSIONS: UHP angioplasty was safe and effective for treatment
      of stent-related resistant PA stenosis in this series; the ability to fracture
      maximally expanded stents may extend the utility of stents in the pediatric
      population.

PMID- 20031694
TI  - Percutaneous coronary intervention with stent implantation versus coronary artery
      bypass surgery for treatment of left main coronary artery disease: is it time to
      change guidelines?
AB  - On the basis of clinical trials comparing coronary-artery bypass grafting (CABG)
      with medical therapy, current guideline recommend CABG as the treatment of choice
      for patients with asymptomatic ischemia, stable angina, or unstable angina/non-ST
      elevation myocardial infarction who have left main coronary artery disease.
      Percutaneous coronary intervention can be selectively performed in patients who
      are candidates for revascularization but who are ineligible for CABG. However,
      because of advances in periprocedural and postprocedural medical care in patients
      undergoing either CABG or percutaneous coronary intervention with stenting, new
      evaluation, and a review of current indications, may be required to determine the
      standard of care for patients with left main coronary artery disease. Current
      evidences indicate that stenting results in mortality and morbidity rates that
      compared favorably with those seen after CABG, suggesting that a current
      guideline (the Class III recommendation of percutaneous coronary intervention for
      unprotected left main coronary artery disease) may no longer be justified. Data
      from several extensive registries and a large clinical trial may have prompted
      many interventional cardiologists to select percutaneous coronary intervention
      with stenting as an alternative revascularization strategy for such patients. In
      addition, these data may inform future guidelines and support the need for well
      designed, adequately powered, prospective, randomized trials comparing the 2
      revascularization strategies. The cumulative evidence from ongoing and future
      clinical trials will change the current clinical practice of revascularization
      for unprotected left main coronary artery disease, which was introduced several
      decades ago and which has continued to date without major revision.

PMID- 20031695
TI  - Coronary intervention in 2009: are women no different than men?

PMID- 20031696
TI  - Epinephrine treatment of anaphylaxis: an extraordinary case of very late acute
      stent thrombosis.

PMID- 20031697
TI  - Letter by Brugaletta et al. regarding article, "Interference of drug-eluting
      stents and endothelium-dependent coronary vasomotion: evidence for device
      specific responses".

PMID- 20031699
TI  - Not just big kids: closing atrial septal defects in adults older than 60 years.

PMID- 20031700
TI  - Percutaneous closure of atrial septal defects: echocardiographic and functional
      results in patients older than 60 years.
AB  - BACKGROUND: Percutaneous closure of atrial septal defects is well established in
      children and adults and has been found to improve symptoms and positively
      influence right-heart remodeling. The aim of this study was to evaluate the
      efficacy and long-term outcome in adult patients older than 60 years. METHODS AND
      RESULTS: The study population comprised 96 patients in the age group of 60 to 84
      years. Percutaneous closure was performed effectively in all patients. Functional
      capacity according to New York Heart Association functional class and peak oxygen
      uptake (VO(2)max) in the cardiopulmonary exercise testing improved significantly
      after atrial septal defects closure, especially in patients with a pulmonary-to
      systemic flow ratio >2. Echocardiographic measurements of the right ventricular
      end-diastolic diameter showed a significant decrease. No device-associated
      complications were observed, but in 16 patients, paroxysmal atrial fibrillation
      occurred after device implantation. CONCLUSIONS: Percutaneous atrial septal
      defects closure can be performed safely and with minimal risk even in elderly
      patients. They profit in terms of symptom reduction, improvement of exercise
      capacity, and right-heart remodeling.

PMID- 20031701
TI  - Immunohistochemical characterization of neotissues and tissue reactions to septal
      defect-occlusion devices.
AB  - BACKGROUND: We sought to evaluate tissue reactions within and at the surface of
      devices for interventional therapy of septal defects and to identify antigen
      characteristics of neotissues. METHODS AND RESULTS: Atrial or ventricular septal
      defect-occlusion devices (Amplatzer, n=7; Cardioseal/Starflex, n=3) were
      processed using a uniform protocol after surgical removal from humans
      (implantation time, 5 days to 4 years). Devices were fixed in formalin and
      embedded in methylmethacrylate. Serial sections were obtained by sectioning with
      a diamond cutter and grinding, thus saving the metal/tissue interface for
      histologic evaluation. Immunohistochemical staining was performed using
      conventional protocols. Superficial endothelial cells stained positive for von
      Willebrand factor. Within the newly formed tissues, fibroblast-like cells were
      identified with a time-dependent expression of smooth muscle cell maturation
      markers (smooth muscle actin, smooth muscle myosin, h-caldesmon, and desmin)
      beside extracellular matrix components. Neovascularization of the newly formed
      tissues was demonstrated with the typical immunohistochemical pattern of
      capillaries and small vessels. Inflammatory cells could be identified as
      macrophages (CD68+) and both T-type and B-type lymphocytes (CD3+, CD79+).
      CONCLUSIONS: This is the first presentation of results from serial
      immunohistochemical staining of a collection of explanted human septal-occlusion
      devices. A time-dependent maturation pattern of the fibroblast-like cells in the
      neotissues around the implants could be described. Neoendothelialization was seen
      in all specimens with implantation times of 10 weeks or more. The time course of
      neoendothelialization, as seen in our study, further supports the clinical
      practice of anticoagulant or antiplatelet therapy for 6 months after
      implantation. This time interval should be sufficient to prevent thromboembolic
      events due to thrombus formation at the foreign surface of cardiovascular
      implants.

PMID- 20031702
TI  - Coronary spasm preferentially occurs at branch points: an angiographic comparison
      with atherosclerotic plaque.
AB  - BACKGROUND: Coronary spasm plays an important role in the pathogenesis of
      ischemic heart disease. However, similarities and differences between coronary
      spasm and atherosclerosis are not known. We examined the angiographic
      characteristics of coronary spasm in comparison with those of atherosclerosis.
      METHODS AND RESULTS: Thirty-two left anterior descending arteries, 11 left
      circumflex arteries, and 23 right coronary arteries with spasm and
      atherosclerotic plaque were analyzed for the localization of spasm in comparison
      with that of plaque in 47 patients (38 men and 9 women, mean age 66.8+/-10.3
      yrs). Spasm predominantly occurred at the branch point as compared with plaque in
      each of the 3 arteries (76.7% versus 23.3%, P<0.0001; 72.7% versus 9.1%, P<0.039;
      and 60.0% versus 10.0%, P=0.002, in the left anterior descending, left
      circumflex, and right coronary arteries, respectively). Spasm involved the
      proximal segment less frequently as compared with plaque in each of the 3
      arteries (56.7% versus 93.3%, P<0.0001; 18.2% versus 81.8%, P=0.016; and 15.0%
      versus 75.0%, P<0.0001 in the left anterior descending, left circumflex, and
      right coronary arteries, respectively). Most spasms occurred at the nonplaque
      site in each of the 3 arteries (73.3%, P=0.018; 100%, P<0.0001; and 75.0%,
      P=0.041 in the left anterior descending, left circumflex, and right coronary
      arteries, respectively). CONCLUSIONS: Coronary spasm preferentially occurred at
      branch points and nonplaque sites, whereas the atherosclerotic lesion was
      predominantly localized at the nonbranch points of the curved proximal segments.
      Coronary spasm may thus be a manifestation of a distinct type of arteriosclerosis
      different from the lipid-laden coronary atherosclerosis.

PMID- 20031703
TI  - Factors portending endoleak formation after thoracic aortic stent-graft repair of
      complicated aortic dissection.
AB  - BACKGROUND: Endoleaks after stent-graft repair of aortic dissections are poorly
      understood but seem substantially different from those seen after aneurysm
      repair. We studied anatomic and clinical factors associated with endoleaks in
      patients who underwent stent-graft repair of complicated type B aortic
      dissections. METHODS AND RESULTS: From 2000 to 2007, 37 patients underwent stent
      graft repair of acute (< or =14 days; n=23), subacute (15 to 90 days; n=10) or
      chronic (>90 days; n=4) complicated type B aortic dissections using the Gore
      Thoracic Excluder (n=17) or TAG stent-grafts (n=20) under an investigator
      sponsored protocol. Endoleaks were classified as imperfect proximal seal, flow
      through fenestrations or branches, or complex (both). Variables studied included
      coverage of the left subclavian artery, aortic curvature, completeness of
      proximal apposition, dissection chronicity, and device used. Endoleaks were found
      during follow-up (mean, 22 months) in 59% of patients, and they were associated
      with coverage of the left subclavian artery (complex, P<0.001), small radius of
      curvature (type 1 and complex, P=0.05), and greatest length of unapposed proximal
      stent graft (complex, P<0.0001). During follow-up, 10 endoleaks resolved
      spontaneously, 6 required reintervention for false lumen dilatation, and 2 were
      stable without clinical consequences. CONCLUSIONS: Endoleaks are common after
      stent-graft repair of aortic dissection and may lead to false lumen enlargement
      necessitating reintervention. Anatomic complexities such as acute aortic
      curvature and covered side branches were associated with endoleaks, illustrating
      the need for dissection-specific device development.

PMID- 20031705
TI  - Retrograde percutaneous recanalization of chronic total occlusion of the coronary
      arteries: procedural outcomes and predictors of success in contemporary practice.
AB  - BACKGROUND: Retrograde approach through collaterals has been introduced for
      percutaneous recanalization of chronic total occlusion (CTO) of the coronary
      arteries. We investigated the safety and efficacy of retrograde approaches used
      for percutaneous recanalization of CTO in a consecutive series of patients.
      METHODS AND RESULTS: We studied 157 consecutive patients who underwent retrograde
      CTO recanalization between 2003 and 2008 at a single center. A total of 118
      (75.2%) of these patients have had previously failed antegrade attempts. Septal,
      epicardial, and saphenous vein graft collaterals were used in 67.5%, 24.8%, and
      7.6% of cases, respectively. Collateral channel was crossed by guide wire
      successfully in 115 (73.2%) cases, and the procedure was successful by retrograde
      approach in 103 (65.6%) cases. Collateral channels (CCs) were graded as follows:
      CC0, no continuous connection; CC1, continuous thread-like connection; and CC2,
      continuous, small sidebranch-like connection. CC1, collateral tortuosity < 90
      degrees , and angle with recipient vessel < 90 degrees (P<0.0001) were
      significant predictors of success. Epicardial channel use (P=0.01), CC0,
      corkscrew channel (P<0.0001), angle with recipient vessel > 90 degrees
      (P=0.0007), and nonvisibility of connection with recipient vessel were found to
      be significant predictors of procedural failure. The CC dissection was observed
      in 6 patients, with 1 needing coil embolization and others who were managed
      conservatively. The major adverse cardiac events were low, with 1 coronary artery
      bypass graft, 1 Q-wave myocardial infarction, 5 non-Q-wave myocardial
      infarctions, and no deaths in this group of patients. CONCLUSIONS: The retrograde
      approach in CTO percutaneous coronary intervention is effective in recanalizing
      CTO. The success rate by retrograde approach was 65.6%, and final success was 85%
      in this group with acceptable overall adverse events. We have identified
      predictors of failure related to collateral morphology.

PMID- 20031704
TI  - A randomized controlled trial of angiography versus intravascular ultrasound
      directed bare-metal coronary stent placement (the AVID Trial).
AB  - BACKGROUND: AVID (Angiography Versus Intravascular ultrasound-Directed stent
      placement) is a multicenter, randomized controlled trial designed to assess the
      effect of intravascular ultrasound (IVUS)-directed stent placement on the 12
      month rate of target lesion revascularization (TLR). METHODS AND RESULTS: After
      elective coronary stent placement and an optimal angiographic result (<10%
      stenosis), 800 patients were randomized to Angiography- or IVUS-directed therapy.
      Blinded IVUS was performed in the Angiography group without further therapy. In
      the IVUS group, IVUS criteria for optimal stent placement (<10% area stenosis,
      apposition, and absence of dissection) were applied. Final minimum stent area was
      6.90+/-2.43 mm(2) in the Angiography group and 7.55+/-2.82 mm(2) in the IVUS
      group (P=0.001). In the IVUS group, only 37% with inadequate expansion (<90%)
      received further therapy. The 12-month TLR rate was 12.0% in the Angiography
      group and 8.1% in the IVUS group (P=0.08, 95% confidence level [CI], [-8.3% to
      0.5%]). When vessels with a distal reference diameter <2.5 mm by core laboratory
      angiography measurement were excluded from analysis, the 12-month TLR rate was
      10.1% in the Angiography group and 4.3% in the IVUS group (P=0.01, 95% CI, [
      10.6% to -1.2%]). With a pre-stent angiographic stenosis of > or =70%, the TLR
      rate was lower in the IVUS group compared with the Angiography group (3.1% versus
      14.2%; P=0.002; 95% CI, [-18.4% to -4.2%]). CONCLUSIONS: IVUS-directed bare-metal
      stent placement results in larger acute stent dimensions without an increase in
      complications and a significantly lower 12-month TLR rate for vessels > or =2.5
      mm by angiography and for vessels with high-grade pre-stent stenosis. However,
      for the entire sample analyzed on an intention-to-treat basis, IVUS-directed bare
      metal stent placement does not significantly reduce the 12-month TLR rate when
      compared with stent placement guided by angiography alone. In addition, IVUS
      evaluation of adequate stent expansion is underutilized by experienced operators.

PMID- 20031706
TI  - Frequency and clinical consequences associated with sidebranch occlusion during
      stent implantation using zotarolimus-eluting and paclitaxel-eluting coronary
      stents.
AB  - BACKGROUND: Myocardial infarction (MI) after drug-eluting stent placement has
      been associated with an unfavorable late prognosis. Although the etiology of
      periprocedural MI is multifactorial, sidebranch occlusion may be an important
      contributing factor. We sought to identify the incidence of sidebranch occlusion
      during zotarolimus-eluting stent (ZES) and paclitaxel-eluting stent (PES)
      placement and to relate sidebranch occlusion to the occurrence of periprocedural
      MI. METHODS AND RESULTS: Angiograms were reviewed from patients randomly assigned
      to treatment with a ZES (597 patients; 943 sidebranches) or a PES (619 patients;
      977 sidebranches). Sidebranch occlusion was defined as Thrombolysis in Myocardial
      Infarction flow grade 0 or 1. Sidebranch occlusion was correlated with frequency
      of MI, as assessed by the creatine phosphokinase MB isoenzyme. Sidebranch
      occlusion occurred less often after the first stent deployment in patients
      treated with ZES (2.2%) than in patients treated with PES (4.0%; P=0.032). A
      similar reduction in the frequency of sidebranch occlusion at any point during
      the procedure was found in patients treated with ZES (2.9% versus 4.8% in PES
      patients; P=0.042). Multivariable predictors of sidebranch occlusion included
      baseline sidebranch stenosis, complex lesion morphology, smaller baseline minimal
      lumen diameters, and the use of a PES. Of the 20 patients with MI within 30 days
      of the procedure, 30% had evidence of sidebranch occlusion during the stent
      procedure. CONCLUSIONS: Patients treated with ZES were less likely to develop
      sidebranch occlusion during stent placement than patients treated with PES. Less
      frequent sidebranch occlusion with ZES may have contributed to the lower
      frequency rates of periprocedural MI in this study.

PMID- 20031707
TI  - Percutaneous treatment of mitral regurgitation.

PMID- 20031708
TI  - Anomalous origin of left coronary artery from the left ventricle.

PMID- 20031709
TI  - Emergency percutaneous coronary intervention in the setting of a single left
      coronary ostium.

PMID- 20031710
TI  - The cart and the horse: the advancing technology of carotid artery stenting.

PMID- 20031711
TI  - Unprotected left main intervention: the light at the end of the tunnel?

PMID- 20031712
TI  - Thirty-day outcomes for carotid artery stenting in 6320 patients from 2
      prospective, multicenter, high-surgical-risk registries.
AB  - BACKGROUND: The American Heart Association has established guidelines for
      acceptable 30-day death and stroke rates for patients with severe carotid disease
      undergoing standard-risk carotid endarterectomy: <3% for asymptomatic lesions and
      <6% for symptomatic lesions. To date, carotid artery stenting has not
      demonstrated these outcomes in multicenter, prospective assessments of high
      surgical-risk patients. METHODS AND RESULTS: Data from 2 prospective, multicenter
      (280 US sites, 672 operators), postmarket surveillance studies in high-surgical
      risk patients were analyzed: 2145 patients from the Emboshield and Xact Post
      Approval Carotid Stent Trial (EX) and 4175 patients from the Carotid
      ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (C2). Both studies
      had pre- and postprocedure neurological evaluation and independent adjudication
      of neurological events. The overall 30-day death and stroke rate was 4.1% (95%
      CI, 3.3% to 5.0%) for EX and 3.4% (95% CI, 2.9% to 4.0%) for C2. In the
      population comparable with American Heart Association guidelines (<80 years), the
      combined 30-day death and stroke rate was 5.3% (95% CI, 3.6% to 7.4%) for
      symptomatic patients and 2.9% (95% CI, 2.4% to 3.4%) for asymptomatic patients,
      independent of unfavorable risk factors (anatomic or physiologic); in patients
      >/=80 years, this rate was 10.5% (95% CI, 6.3% to 16.0%) and 4.4% (95% CI, 3.3%
      to 5.7%), respectively. In subjects with anatomic features unfavorable for
      surgery, the 30-day death and stroke rates were 1.7% (95% CI, 0.0% to 8.9%) and
      2.7% (95% CI, 1.3% to 4.9%) for symptomatic and asymptomatic cohorts,
      respectively, independent of age. CONCLUSIONS: Outcomes for carotid artery
      stenting in nonoctogenarian high-surgical-risk patients have improved since the
      pivotal Food and Drug Administration approval trials, and have achieved American
      Heart Association standards in both symptomatic and asymptomatic lesions.

PMID- 20031713
TI  - Impact of intravascular ultrasound guidance on long-term mortality in stenting
      for unprotected left main coronary artery stenosis.
AB  - BACKGROUND: Although intravascular ultrasound (IVUS) guidance has been useful in
      stenting for unprotected left main coronary artery stenosis, its impact on long
      term mortality is still unclear. METHODS AND RESULTS: In the MAIN-COMPARE
      registry, patients with unprotected left main coronary artery stenosis in a
      hemodynamically stable condition underwent elective stenting under the guidance
      of IVUS (756 patients) or conventional angiography (219 patients). Patients with
      acute myocardial infarction were excluded. The 3-year outcomes between the 2
      groups were primarily compared using propensity-score matching in the entire and
      separate populations according to stent type. In 201 matched pairs of the overall
      population, there was a tendency of lower risk of 3-year morality with IVUS
      guidance compared with angiography guidance (6.0% versus 13.6%, log-rank P=0.063;
      hazard ratio, 0.54; 95% CI, 0.28 to 1.03; Cox-model P=0.061). In particular, in
      145 matched pairs of patients receiving drug-eluting stent, the 3-year incidence
      of mortality was lower with IVUS guidance as compared with angiography guidance
      (4.7% versus 16.0%, log-rank P=0.048; hazard ratio, 0.39; 95% CI, 0.15 to 1.02;
      Cox model P=0.055). In contrast, the use of IVUS guidance did not reduce the risk
      of mortality in 47 matched pairs of patients receiving bare-metal stent (8.6%
      versus 10.8%, log-rank P=0.35; hazard ratio, 0.59; 95% CI, 0.18 to 1.91; Cox
      model P=0.38). The risk of myocardial infarction or target vessel
      revascularization was not associated with the use of IVUS guidance. CONCLUSIONS:
      Elective stenting with IVUS guidance, especially in the placement of drug-eluting
      stent, may reduce the long-term mortality rate for unprotected left main coronary
      artery stenosis when compared with conventional angiography guidance.

PMID- 20031714
TI  - Long-term paclitaxel-eluting stent outcomes in elderly patients.
AB  - BACKGROUND: Although drug-eluting stents have become a mainstay of percutaneous
      coronary intervention, information about drug-eluting stents outcomes in elderly
      patients is limited. Data from the paclitaxel-eluting stent (PES) trials and
      registries were pooled to assess PES benefits relative to advancing patient age,
      including comparison with bare-metal stents. METHODS AND RESULTS: Data from 5
      randomized trials (2271 patients with PES, 1397 patients with bare-metal stents)
      and from 2 postmarket registries (7492 patients with PES) were pooled separately.
      Each dataset was stratified into age groups: <60, 60 to 70, and >70 years. At
      baseline, patients aged >70 years in both datasets had significantly more adverse
      characteristics than younger patients. Through 5 years, trial data showed that
      patients aged >70 years had higher death rates, but comparable rates of
      myocardial infarction, stent thrombosis, and target lesion revascularization with
      younger patients. Compared with patients with bare-metal stents, patients with
      PES aged >70 years had comparable rates of death, myocardial infarction, and
      stent thrombosis but a significantly lower target lesion revascularization rate
      (22.2 versus 10.2, P<0.001). These findings were echoed in the registry data
      through 2 years that showed that PES patients aged >70 years had significantly
      higher death rates, but lower myocardial infarction, stent thrombosis, and target
      lesion revascularization rates, compared with younger patients. Although the
      mortality rates of patients aged >70 years were higher than those of younger
      patients, they were comparable with those of age- and gender-matched norms in the
      general population. CONCLUSIONS: This analysis of almost 10 000 patients
      demonstrated that percutaneous coronary intervention with PES is a safe and an
      effective treatment option that should not be withheld based on age.

PMID- 20031716
TI  - Impact of NAD(P)H oxidase-derived reactive oxygen species on coronary arterial
      remodeling: a comparative intravascular ultrasound and histochemical analysis of
      atherosclerotic lesions.
AB  - BACKGROUND: Coronary arterial remodeling, which is a response to the growth of
      atherosclerotic plaques, is associated with plaque vulnerability. Oxidative
      stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the
      vasculature also plays a crucial role in the pathogenesis of atherosclerosis
      based cardiovascular disease. In this study, the relationship between coronary
      arterial remodeling and ROS generation was examined by comparing
      preinterventional intravascular ultrasound findings of atherosclerotic lesions to
      the histochemical findings of corresponding specimens obtained by directional
      coronary atherectomy. METHODS AND RESULTS: Predirectional coronary atherectomy
      intravascular ultrasound images of 49 patients were analyzed. The remodeling
      index was calculated by dividing the target-lesion external elastic membrane
      cross-sectional area by the reference-segment external elastic membrane cross
      sectional area. Expansive remodeling was defined as a remodeling index of >1.0.
      ROS generation and NAD(P)H oxidase p22(phox) expression in directional coronary
      atherectomy specimens were evaluated using the dihydroethidium staining method
      and immunohistochemistry as the ratio of the positive area to the total surface
      area in each specimen, respectively. ROS generation and p22(phox) expression were
      significantly greater in lesions with expansive remodeling than in lesions
      without remodeling (0.18+/-0.12 versus 0.03+/-0.02, P<0.0001, 0.10+/-0.08 versus
      0.04+/-0.05, P=0.0039, respectively). Both ROS generation and p22(phox)
      expression significantly correlated with the intravascular ultrasound-derived
      remodeling index (r=0.77, P<0.0001, r=0.53, P<0.0001, respectively). CONCLUSIONS:
      Simultaneous examination with intravascular ultrasound and immunohistochemistry
      analyses suggests that NAD(P)H oxidase-derived ROS is related to the coronary
      arterial remodeling process associated with plaque vulnerability.

PMID- 20031715
TI  - Randomized comparison of the Nobori Biolimus A9-eluting coronary stent with the
      Taxus Liberte paclitaxel-eluting coronary stent in patients with stenosis in
      native coronary arteries: the NOBORI 1 trial--Phase 2.
AB  - BACKGROUND: The newly developed Nobori coronary stent coated with a bioresorbable
      polymer, polylactic acid, and the antiproliferative agent Biolimus A9 has the
      potential to reduce restenosis by suppressing neointima formation. METHODS AND
      RESULTS: We conducted a randomized (2:1), controlled trial comparing the Biolimus
      A9-eluting stent Nobori and the paclitaxel-eluting stent Taxus Liberte, in 243
      patients (153 Nobori and 90 Taxus) at 29 centers in Europe, Asia, and Australia.
      Patients with previously untreated lesions in up to 2 native coronary arteries
      were considered for enrollment. The primary end point was in-stent late loss at 9
      months, whereas secondary end points included other quantitative coronary
      angiography parameters, such as in-segment late loss and the rate of restenosis
      as well as key intravascular ultrasound parameters. Clinical secondary end points
      were stent thrombosis and composite of major adverse cardiac events comprising
      death, myocardial infarction, and target vessel revascularization. At 9 months,
      the in-stent late loss was significantly lower in the Nobori group compared with
      the Taxus group (0.11+/-0.30 mm versus 0.32+/-0.50 mm) reaching both the primary
      hypothesis of noninferiority of Nobori stent versus Taxus Liberte stent (P<0.001)
      and the secondary hypothesis of superiority (P=0.001). This finding was confirmed
      by a significant reduction in binary restenosis from 6.2% in Taxus to 0.7% in
      Nobori (P=0.02) and neointimal volume obstruction, detected by intravascular
      ultrasound, from 5.5+/-7.2% in Taxus to 1.8+/-5.2% in Nobori (P=0.01). The major
      adverse cardiac events rate was 4.6% in the Nobori and 5.6% in the Taxus cohort
      of patients. The stent thrombosis rate was 0% in the Nobori arm and 4.4% in the
      Taxus arm. CONCLUSIONS: The NOBORI 1 clinical trial confirmed its primary
      hypothesis--noninferiority of the Nobori Biolimus A9-eluting stent versus the
      Taxus Liberte stent in reducing neointimal proliferation. Both stents showed a
      low major adverse cardiac events rate in the studied population.

PMID- 20031717
TI  - Extended follow-up by serial angioscopic observation for bare-metal stents in
      native coronary arteries: from healing response to atherosclerotic transformation
      of neointima.
AB  - BACKGROUND: Although coronary angiograms after bare-metal stent (BMS)
      implantation show late luminal narrowing beyond 4 years, the detailed changes
      inside the BMS have not yet been fully elucidated. METHODS AND RESULTS: Serial
      angiographic and angioscopic examinations were performed immediately (baseline),
      6 to 12 months (first follow-up), and >or=4 years (second follow-up) after
      stenting without target lesion revascularization in 26 segments of 26 patients
      who received BMS deployment for their native coronary arteries. Angioscopic
      observation showed atherosclerotic yellow plaque crushed out by stent struts in
      22 patients (85%) and mural thrombus in 21 patients (81%) at baseline. At first
      follow-up, white neointimal hyperplasia was almost completely buried inside the
      struts, and both yellow plaque and thrombus had decreased in comparison with
      baseline (12% and 4%, respectively; P<0.001). The frequencies of yellow plaque
      and thrombus increased from the first to second follow-ups (58% and 31%,
      respectively; P<0.05). All of the yellow plaques in the second follow-up were
      located not exterior to the struts but protruding from the vessel wall into the
      lumen. Late luminal narrowing, defined as an increasing of percent diameter
      stenosis between the first and second follow-ups, was greater in segments with
      yellow plaque than in those without yellow plaque (18.4+/-17.3% versus 3.6+/
      4.2%, respectively; P=0.011). CONCLUSIONS: This angiographic and angioscopic
      study suggests that white neointima of the BMS may often change into yellow
      plaque over an extended period of time, and atherosclerotic progression inside
      the BMS may contribute to late luminal narrowing.

PMID- 20031718
TI  - Noncardiac surgery and bleeding after percutaneous coronary intervention.
AB  - BACKGROUND: The decision on whether to implant a drug-eluting or bare-metal stent
      during percutaneous coronary intervention (PCI) depends in part on the perceived
      likelihood of the patient developing late stent thrombosis. Noncardiac surgery
      and bleeding are associated with discontinuation of dual antiplatelet therapy and
      with increased stent thrombosis. We assessed the incidence of and predictors for
      subsequent noncardiac surgery and bleeding episodes in patients who had undergone
      PCI. METHODS AND RESULTS: Hospital discharge coding data were used to identify
      all adult patients undergoing public hospital PCI in New Zealand from 1996 to
      2001. Hospital admissions during the ensuing 5 years were analyzed for noncardiac
      surgery and bleeding episodes. Eleven thousand one hundred fifty-one patients
      (age, 62+/-11 years; 30% women) underwent PCI, mainly for an acute coronary
      syndrome (73%). During the 5-year follow-up, 26% of the population underwent at
      least 1 noncardiac surgical procedure (23% orthopedic, 20% abdominal, 12%
      urologic, 10% vascular, 35% others) and 8.6% had at least 1 bleeding episode
      either requiring or occurring during hospitalization. Of those, half were
      gastrointestinal, and one quarter of bleeding events required blood transfusion.
      The main clinical predictors of noncardiac surgery were advanced age, previous
      noncardiac surgery, osteoarthritis, and peripheral vascular disease. A previous
      bleeding admission and age were the strongest predictors of subsequent bleeding.
      CONCLUSIONS: Noncardiac surgery is required frequently after PCI, whereas
      bleeding is less common. Before implanting a drug-eluting or bare-metal stent,
      individual patient risk stratification by the interventional cardiologist should
      include assessment of whether there is an increased likelihood of needing
      noncardiac surgery or developing bleeding.

PMID- 20031719
TI  - Bleeding in patients undergoing percutaneous coronary intervention: the
      development of a clinical risk algorithm from the National Cardiovascular Data
      Registry.
AB  - BACKGROUND: Bleeding in patients undergoing percutaneous coronary intervention
      (PCI) is associated with increased morbidity, mortality, length of
      hospitalization, and cost. We identified baseline clinical characteristics
      associated with bleeding complications after PCI and developed a simplified,
      clinically useful algorithm to predict patient risk. METHODS AND RESULTS: Data
      were analyzed from 302 152 PCI procedures performed at 440 US centers
      participating in the National Cardiovascular Data Registry. As defined by the
      National Cardiovascular Data Registry, bleeding required transfusion, prolonged
      hospital stay, and/or a drop in hemoglobin >3.0 g/dL from any location, including
      percutaneous entry site, retroperitoneal, gastrointestinal, genitourinary, and
      other/unknown location. Bleeding complications occurred in 2.4% of patients. From
      the best-fitting model consisting of 15 clinical elements associated with post
      PCI bleeding in a random 80% training cohort, we developed a parsimonious risk
      algorithm. Predictors of bleeding included age, gender, previous heart failure,
      glomerular filtration rate, peripheral vascular disease, no previous PCI, New
      York Heart Association/Canadian Cardiovascular Society Functional Classification
      class IV heart failure, ST-elevation myocardial infarction, non-ST-elevation
      myocardial infarction, and cardiogenic shock. The parsimonious model was
      validated in the remaining 20% of the population (c-statistic, 0.72) and in
      clinically relevant subgroups of patients. This simplified model was used to
      derive a clinical risk algorithm, with larger numbers corresponding with greater
      risk. In 3 categories, bleeding rates were greater in patients with higher
      estimates (<or=7, 0.7%; 8 to 17, 1.8%; >or=18, 5.1%). CONCLUSIONS: This report
      identifies baseline clinical factors associated with bleeding and proposes a
      clinically useful algorithm to estimate bleeding risk. This model is potentially
      actionable in altering therapeutic decision making and improving outcomes in
      patients undergoing PCI.

PMID- 20031720
TI  - A comparison of abciximab and small-molecule glycoprotein IIb/IIIa inhibitors in
      patients undergoing primary percutaneous coronary intervention: a meta-analysis
      of contemporary randomized controlled trials.
AB  - BACKGROUND: Current guidelines recommend abciximab as the preferred agent for
      patients undergoing primary percutaneous coronary intervention, yet small
      molecule glycoprotein IIb/IIIa inhibitors are more commonly used in clinical
      practice. The objective of our meta-analysis was to evaluate for differences in
      clinical outcome between small-molecule glycoprotein IIb/IIIa inhibitors and
      abciximab in patients with ST-segment elevation myocardial infarction undergoing
      primary percutaneous coronary intervention. METHODS AND RESULTS: Five randomized
      trials (n=2138 patients) comparing tirofiban or eptifibatide with abciximab as an
      adjunctive therapy to primary percutaneous coronary intervention were included in
      this meta-analysis. Summary odds ratios (ORs) for 30-day death, reinfarction, and
      major bleeding were calculated using random- and fixed-effect models. There were
      no differences in 30-day mortality (1.9% for small molecule versus 2.3% for
      abciximab; OR, 0.84; 95% CI, 0.46 to 1.55; P=0.58), reinfarction (1.3% versus
      1.2%; OR, 1.22; 95% CI, 0.51 to 2.91; P=0.69), or major bleeding (1.7% versus
      1.3%; OR, 1.21; 95% CI, 0.58 to 2.49; P=0.61) between the 2 adjunctive
      strategies. Similarly, there was no significant difference in the incidence of
      death (3.9% versus 5%; OR, 0.77; 95% CI, 0.41 to 1.46; P=0.43) or reinfarction on
      follow-up at 8 months between small-molecule glycoprotein IIb/IIIa inhibitors and
      abciximab. CONCLUSIONS: In patients undergoing primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction, no difference in
      outcome could be identified in patients treated with small-molecule glycoprotein
      IIb/IIIa inhibitor or abciximab.

PMID- 20031722
TI  - Long-term outcome of therapeutic neovascularization using peripheral blood
      mononuclear cells for limb ischemia.
AB  - BACKGROUND: Injection of bone marrow mononuclear cells has been reported to
      promote neovascularization of ischemic tissues effectively. We found that
      peripheral blood mononuclear cells were as efficient as bone marrow mononuclear
      cells for the treatment of limb ischemia in animals and showed that this
      treatment was feasible and safe in no-option patients with limb ischemia.
      However, the long-term outcome of such therapy has not been investigated. METHODS
      AND RESULTS: We retrospectively analyzed the data for 42 patients who were
      treated between July 2002 and December 2005 by using the log-rank test, the
      Kaplan-Meier method, and the Cox proportional hazard model. Improvement of
      ischemic symptoms was observed in 60% to 70% of the patients. The annual rate of
      major amputation was decreased markedly by treatment. Improvement of ischemic
      symptoms was less marked in arteriosclerosis obliterans (ASO) patients on
      dialysis compared with nonhemodialysis ASO or thromboangiitis obliterans
      patients. Indeed, the survival rate of these patients was lower than that of
      nonhemodialysis ASO or thromboangiitis obliterans patients. Major adverse events
      such as death, major amputation, and cardiovascular events occurred mostly in ASO
      patients, and most of them were on dialysis. There was no significant difference
      in the cardiovascular event-free rate between responders and nonresponders. The
      survival rate of younger responders was better than that of nonresponders.
      CONCLUSIONS: Although this study was not placebo-controlled and these initial
      results were from a retrospective analysis, injection of peripheral blood
      mononuclear cells might be safe and potentially effective for the treatment of
      limb ischemia, but caution is needed when managing ASO patients on dialysis.

PMID- 20031721
TI  - Lack of correlation between noninvasive stress tests and invasive coronary
      vasomotor dysfunction in patients with nonobstructive coronary artery disease.
AB  - BACKGROUND: Despite a nonobstructive coronary angiogram, many patients may still
      have an abnormal coronary vasomotor response to provocation and to myocardial
      demand during stress. The ability of noninvasive stress tests to predict coronary
      vasomotor dysfunction in patients with nonobstructive coronary artery disease is
      unknown. METHODS AND RESULTS: All patients with nonobstructive coronary artery
      disease who had invasive coronary vasomotor assessment and a noninvasive stress
      test (exercise ECG, stress echocardiography, or stress nuclear imaging) within 6
      months of the cardiac catheterization with provocation at our institution were
      identified (n=376). Coronary vasomotor dysfunction was defined as a percentage
      increase in coronary blood flow of <or=50% to intracoronary acetylcholine
      (endothelium-dependent dysfunction) and/or a coronary flow reserve ratio of
      <or=2.5 to intracoronary adenosine (endothelium-independent dysfunction). We
      determined the sensitivity and specificity of various noninvasive stress tests to
      predict coronary vasomotor dysfunction in these patients. On invasive testing,
      233 patients (63%) had coronary vasomotor dysfunction, of which 187 patients
      (51%) had endothelium-dependent dysfunction, 109 patients (29%) had endothelium
      independent dysfunction, and 63 patients (17%) had both. On noninvasive stress
      testing, 157 (42%) had a positive imaging study and 56 (15%) a positive ECG
      stress test. The noninvasive stress tests had limited diagnostic accuracy for
      predicting coronary vasomotor dysfunction (41% sensitivity [95% CI, 34 to 47] and
      57% specificity [95% CI, 49 to 66]), endothelium-dependent dysfunction (41%
      sensitivity [95% CI, 34 to 49] and 58% specificity [95% CI, 50 to 65]), or
      endothelium-independent dysfunction (46% sensitivity [95% CI, 37 to 56] and 61%
      specificity [95% CI, 54 to 67]). The exercise ECG test was more specific but less
      sensitive than the imaging tests. CONCLUSIONS: This study suggests that a
      negative noninvasive stress test does not rule out coronary vasomotor dysfunction
      in symptomatic patients with nonobstructive coronary artery disease. This
      underscores the need for invasive assessment or novel more sensitive noninvasive
      imaging for these patients.

PMID- 20031723
TI  - Bioabsorbable coronary stents.

PMID- 20031724
TI  - Resolution of iatrogenic aortic dissection illustrated by computed tomography.

PMID- 20031725
TI  - "Intracoronary whirling current phenomenon" and thrombus formation after
      sirolimus-eluting stent implantation visualized by optical coherence tomography.

PMID- 20031726
TI  - Severe multivessel coronary vasospasm and left ventricular ballooning syndrome.

PMID- 20031727
TI  - The wishful thinking of indirect mitral annuloplasty: will it ever become a
      reality?

PMID- 20031728
TI  - Off-label use and the spectre of drug-eluting stent thrombosis.

PMID- 20031729
TI  - Percutaneous transvenous mitral annuloplasty: initial human experience with a
      novel coronary sinus implant device.
AB  - BACKGROUND: We assessed the safety and feasibility of permanent implantation of a
      novel coronary sinus mitral repair device (PTMA, Viacor Inc). METHODS AND
      RESULTS: Symptomatic (New York Heart Association class 2 or 3) patients with
      primarily functional mitral regurgitation (MR) were included. A diagnostic PTMA
      procedure was performed in the coronary sinus venous continuity. MR was assessed
      and the PTMA device adjusted to optimize efficacy. If MR reduction (> or =1
      grade) was observed, placement of a PTMA implant was attempted. Implanted
      patients were evaluated with echocardiographic, quality of life, and exercise
      capacity metrics. Nineteen patients received a diagnostic PTMA study. Diagnostic
      PTMA was effective in 13 patients (MR grade 3.2+/-0.6 reduced to 2.0+/-1.0), and
      PTMA implants were placed in 9 patients. Four devices were removed uneventfully
      (7, 84, 197, and 216 days), 3 for annuloplasty surgery due to observed PTMA
      device migration and/or diminished efficacy. No procedure or device-related major
      adverse events with permanent sequela were observed in any of the diagnostic or
      implant patients. Sustained reductions of mitral annulus septal-lateral dimension
      from 3D echo reconstruction dimensions were observed (4.0+/-1.2 mm at 3 months).
      CONCLUSIONS: Percutaneous implantation of the PTMA device is feasible and safe.
      Acute results demonstrate a possibly meaningful reduction of MR in responding
      patients. Sustained favorable geometric modification of the mitral annulus has
      been observed, though reduction of MR has been limited. The PTMA method warrants
      continued evaluation and development.

PMID- 20031730
TI  - Drug-eluting stent thrombosis in routine clinical practice: two-year outcomes and
      predictors from the TAXUS ARRIVE registries.
AB  - BACKGROUND: Stent thrombosis (ST) is an uncommon but serious complication of drug
      eluting and bare metal stents. To assess drug-eluting stent ST in contemporary
      practice, we analyzed 2-year data from the 7492-patient ARRIVE registry. METHODS
      AND RESULTS: Patients were enrolled at the initiation of percutaneous coronary
      intervention with no inclusion/exclusion criteria beyond use of the paclitaxel
      eluting TAXUS stent. Two-year follow-up was 94% with independent adjudication of
      major cardiac events. A second, autonomous committee adjudicated Academic
      Research Consortium (ARC) definite/probable ST. Cumulative 2-year ARC-defined ST
      was 2.6% (1.0% early ST [<30 days], 0.7% late ST [31 to 365 days], and 0.8% very
      late ST [>1 year]). Simple-use (single-vessel and single-stent) cases had lower
      rates than expanded use (broader patient/lesion characteristics, 2-year
      cumulative: 1.4% versus 3.3%, P<0.001; early ST: 0.4% versus 1.4%, P<0.001; late
      ST: 0.5% versus 0.8%, P=0.14; very late ST: 0.4% versus 1.0%, P=0.008). Within 7
      days of ST, 23% of patients died; 28% suffered Q-wave myocardial infarction.
      Mortality was higher with early ST (39%) than late ST (12%, P<0.001) or very late
      ST (13%, P<0.001). Multivariate analysis showed anatomic factors increased early
      ST (lesion >28 mm, lesion calcification) and late ST (vessel <3.0 mm); biological
      factors increased very late ST (renal disease, prior brachytherapy). Although
      early ST (71.4%) and very late ST (23.1%) patients had dual antiplatelet therapy
      at the time of ST, premature thienopyridine discontinuation was a strong
      independent predictor of both. CONCLUSIONS: The relative risks of early and late
      ST differ. Knowledge of ST risk for specific subgroups may guide
      revascularization options until the completion of randomized trials in these
      broad populations.

PMID- 20031731
TI  - Catheter-based delivery of fluid paclitaxel for prevention of restenosis in
      native coronary artery lesions after stent implantation.
AB  - BACKGROUND: Stents eluting antiproliferative drugs reduce the incidence of
      restenosis but delay healing of the vascular wall. We assessed the safety and
      efficacy of catheter-based local delivery of fluid paclitaxel in patients with
      coronary de novo stenoses after implantation of a bare metal stent. METHODS AND
      RESULTS: We conducted a prospective, randomized trial comparing the local
      delivery of fluid paclitaxel after bare metal stent implantation (group I) with
      the implantation of a bare metal stent (group II) and the implantation of a
      paclitaxel-eluting stent (group III) in 204 patients. The primary end point was
      in-stent late lumen loss. Secondary end points included binary restenosis rate
      >50%, minimal lumen diameter, diameter stenosis, and a composite clinical end
      point (major adverse cardiac events and revascularization of the target lesion) 6
      months after intervention. At 6 months, angiography showed an in-stent late lumen
      loss of 0.61+/-0.44 mm in group I versus 0.99+/-0.72 mm in group II (I versus II,
      P=0.0006) and 0.44+/-0.48 mm in group III (noninferiority of I versus III,
      P=0.023). The 1-sided 95% CI for the true difference of the means of in-stent
      late lumen loss in groups I and III was -infinity to 0.3174188. The cumulative
      overall rate of major cardiac events was 13.4% in group I, 26.8% in group II, and
      14.9% in group III. Target lesion revascularization rate was 13.4% (group I),
      22.1% (group II), and 13.4% (group III). CONCLUSIONS: Additional
      antiproliferative treatment of de novo lesions in native coronary arteries with
      catheter-based delivery of fluid paclitaxel after bare metal stenting was safe
      and significantly reduced neointimal proliferation, restenosis, and clinical
      events compared with bare metal stent implantation alone.

PMID- 20031732
TI  - Usefulness of the SYNTAX score for predicting clinical outcome after percutaneous
      coronary intervention of unprotected left main coronary artery disease.
AB  - BACKGROUND: The SYNTAX score (SXscore) has been proposed recently as a valuable
      tool to characterize the coronary vasculature prospectively with respect to the
      number of lesions and their functional impact, location, and complexity. However,
      the prognostic value of SXscores in patients undergoing percutaneous coronary
      intervention of the left main artery has not been validated. METHODS AND RESULTS:
      We applied the SXscore in 255 consecutive patients who underwent percutaneous
      coronary intervention for left main disease and explored its performance with
      respect to their clinical outcome. Univariate and multivariate Cox proportional
      hazard regression analyses were performed to evaluate the relation between the
      SXscore and the incidence of cardiac mortality, the primary end point of the
      study, and major adverse cardiac events (MACE). At 1 year, the SXscore
      significantly predicted the risk of cardiac death (hazard ratio, 1.12/unit
      increase; 95% CI, 1.06 to 1.18; P<0.001) and MACE (hazard ratio, 1.59/unit
      increase; 95% CI, 1.02 to 2.48; P=0.043). After adjustment for potential
      confounders, a higher SXscore remained significantly associated with cardiac
      mortality (adjusted hazard ratio, 1.15; 95% CI, 1.05 to 1.26; P=0.003) and MACE
      (adjusted hazard ratio, 1.06; 95% CI, 1.02 to 1.10; P=0.005). C-indexes for
      SXscores in terms of cardiac death and MACE were 0.83 and 0.64, respectively.
      Using classification tree analysis, discrimination levels of 34 and 37 were
      identified as the optimal cutoff to distinguish between patients at low and high
      risk of cardiac death and MACE, respectively. CONCLUSIONS: The SXscore is a
      useful tool to predict cardiac mortality and MACE in patients undergoing
      percutaneous revascularization of the left main coronary artery.

PMID- 20031733
TI  - The adverse long-term impact of renal impairment in patients undergoing
      percutaneous coronary intervention in the drug-eluting stent era.
AB  - BACKGROUND: An observational study determining the long-term impact of chronic
      kidney disease (CKD) on patients undergoing percutaneous coronary intervention at
      a tertiary cardiac referral center. CKD is associated with poor in-hospital
      outcomes after percutaneous coronary intervention, but its effect beyond 1 year,
      particularly in the drug-eluting stent (DES) era, has not been reported. METHODS
      AND RESULTS: Baseline creatinine was available for 11,953 patients entered into a
      prospective registry (April 2000 to September 2007). Patients were stratified:
      those with or without at least moderate CKD (creatinine clearance, <60 mL/min).
      Follow-up data were obtained through linkage to a provincial registry. Kaplan
      Meier analysis was performed. Cox multiple-regression analysis identified
      independent predictors of late mortality and major adverse cardiac events (MACE)
      and examined the association between DES use and late outcomes in the presence or
      absence of CKD. CKD was present in 3070 patients (25.7%). In-hospital mortality
      and MACE were significantly increased in CKD (3.34% versus 0.44%, P<0.001 and
      5.73% versus 2.2%, P<0.001). Survival and MACE-free survival at 7 years were
      reduced (64.5+/-1.4% versus 89.4+/-0.5%, P<0.001; 44.0+/-1.4% versus 63.4+/-0.8%,
      P<0.001). CKD was an independent predictor of late mortality and MACE (hazard
      ratio [HR]: 2.18, CI: 1.90 to 2.49, P<0.0001; HR: 1.37, CI: 1.25 to 1.49,
      P<0.0001). DES use was associated with a significant reduction in both (HR: 0.71,
      CI: 0.60 to 0.83, P<0.0001; HR: 0.70, CI: 0.63 to 0.78, P<0.0001). In patients
      with CKD, DES use was associated with reduced revascularization (HR: 0.68, CI:
      0.53 to 0.88, P=0.004) and reduced MACE (HR: 0.81, CI: 0.69 to 0.95, P=0.011) but
      not reduced mortality (HR: 0.85, CI: 0.69 to 1.05, P=0.1). CONCLUSIONS: In a
      large registry of "all comers" for percutaneous coronary intervention, CKD was an
      independent predictor of adverse late outcomes. DES use may be associated with
      improved long-term outcomes in this high-risk cohort, but further prospective
      studies are required.

PMID- 20031734
TI  - Vascular disease burden and in-hospital outcomes among patients undergoing
      percutaneous coronary intervention in New York State.
AB  - BACKGROUND: The presence of atherosclerosis in extracardiac vascular beds is
      associated with an increased risk of adverse cardiovascular outcomes among stable
      patients with coronary artery disease (CAD). However, there is little data
      regarding the impact of the presence and extent of vascular disease on outcomes
      in patients with CAD undergoing percutaneous coronary intervention. METHODS AND
      RESULTS: We analyzed 69,045 consecutive patients from the New York State Coronary
      Angioplasty Reporting System database who underwent percutaneous coronary
      intervention between 1998 and 1999. Vascular disease burden was assessed by
      history of aortoiliac, femoral-popliteal, and carotid disease. Patients were
      stratified into 3 groups: CAD alone, CAD and 1 additional site, and CAD and 2 or
      3 additional sites. A logistic regression model was constructed to determine the
      relation between vascular disease burden and in-hospital mortality. Any history
      of vascular disease was present in 5915 (8.6%) of the population, of whom 4840
      (82%) had CAD and 1 other disease location and 1075 (18%) had CAD and 2 or 3
      other disease locations. There was a significant relationship between the number
      of disease locations and hospital mortality, ranging from 0.7% in patients with
      CAD alone to 2.0% and 2.6% for patients with 1 or >or =2 disease locations,
      respectively (P<0.001). In unadjusted analysis, in-hospital mortality was
      approximately 3-fold higher (odds ratio, 2.89; 95% CI, 2.31 to 3.60; P<0.001) and
      4-fold higher (odds ratio, 3.78; 95% CI, 2.57 to 5.56; P<0.001) for inpatients
      with CAD and additional vascular disease at 1 site and > or =2 sites,
      respectively. After multivariable adjustment, each additional vascular bed
      affected was associated with a 50% increase in in-hospital mortality (odds ratio,
      1.50; 95% CI, 1.27 to 1.78; P<0.001). CONCLUSIONS: Among patients with CAD
      undergoing percutaneous coronary intervention, vascular disease burden is
      associated with higher rates of adverse events and is an independent predictor of
      in-hospital mortality.

PMID- 20031735
TI  - Effect of high-dose intracoronary adenosine administration during primary
      percutaneous coronary intervention in acute myocardial infarction: a randomized
      controlled trial.
AB  - BACKGROUND: Coronary microvascular dysfunction is frequently seen in patients
      with ST-elevation myocardial infarction after primary percutaneous coronary
      intervention. Previous studies have suggested that the administration of
      intravenous adenosine resulted in an improvement of myocardial perfusion and a
      reduction in infarct size. Intracoronary adenosine (bolus of 30 to 60 microg) is
      a guideline-recommended therapy to improve myocardial reperfusion. The effect of
      intracoronary adenosine during primary percutaneous coronary intervention has not
      been investigated in a large randomized trial. METHODS AND RESULTS: Patients
      presenting with acute ST-elevation myocardial infarction were randomized to 2
      bolus injections of intracoronary adenosine (2 x 120 microg in 20 mL NaCl) or
      placebo (2 x 20 mL NaCl). The first bolus injection was given after thrombus
      aspiration and the second after stenting of the infarct-related artery. The
      primary end point was the incidence of residual ST-segment deviation <0.2 mV, 30
      to 60 minutes after percutaneous coronary intervention. Secondary end points were
      ST-segment elevation resolution, myocardial blush grade, Thrombolysis in
      Myocardial Infarction flow on the angiogram after percutaneous coronary
      intervention, enzymatic infarct size, and clinical outcome at 30 days. A total of
      448 patients were randomized to intracoronary adenosine (N=226) or placebo
      (N=222). The incidence of residual ST-segment deviation <0.2 mV did not differ
      between patients randomized to adenosine or placebo (46.2% versus 52.2%, P=NS).
      In addition, there were no significant differences in secondary outcome measures.
      CONCLUSIONS: In this randomized placebo controlled trial enrolling 448 patients
      with ST-elevation myocardial infarction, administration of intracoronary
      adenosine after thrombus aspiration and after stenting of the infarct-related
      artery did not result in improved myocardial perfusion.

PMID- 20031736
TI  - Primary percutaneous coronary angioplasty with and without eptifibatide in ST
      segment elevation myocardial infarction: a safety and efficacy study of
      integrilin-facilitated versus primary percutaneous coronary intervention in ST
      segment elevation myocardial infarction (ASSIST).
AB  - BACKGROUND: Primary percutaneous coronary intervention, if performed promptly, is
      the preferred strategy to restore flow to the infarct-related artery in patients
      with ST-segment elevation myocardial infarction. We sought to determine whether
      eptifibatide, a platelet glycoprotein IIb/IIIa inhibitor, given before
      catheterization would improve clinical outcomes in patients referred for primary
      percutaneous coronary intervention. METHODS AND RESULTS: We randomly assigned a
      total of 400 patients with ST-segment elevation myocardial infarction referred
      for primary percutaneous coronary intervention to treatment initiated before
      cardiac catheterization, with either heparin plus eptifibatide (201 patients) or
      heparin alone (199 patients), in addition to oral aspirin (160 mg) and high-dose
      clopidogrel (600 mg). The primary end point was a composite of death from any
      cause, recurrent myocardial infarction, or recurrent severe ischemia during the
      first 30 days after randomization. At 30 days, the primary end point was reached
      by 13 patients (6.47%) assigned to heparin plus eptifibatide and by 11 patients
      (5.53%) assigned to heparin alone (relative risk, 1.18; 95% CI, 0.52 to 2.70;
      P=0.69). The rates of major or minor bleeding were higher in patients assigned to
      heparin plus eptifibatide than that in patients assigned to heparin alone (22.4%
      versus 14.6%; relative risk, 1.69; 95% CI, 1.01 to 2.83; P=0.04). CONCLUSIONS: In
      patients pretreated with high-dose clopidogrel who were referred for primary PCI,
      treatment with heparin plus eptifibatide, when compared with heparin alone, did
      not improve clinical outcomes and was associated with more bleeding
      complications.

PMID- 20031737
TI  - Two-year clinical, angiographic, and intravascular ultrasound follow-up of the
      XIENCE V everolimus-eluting stent in the treatment of patients with de novo
      native coronary artery lesions: the SPIRIT II trial.
AB  - BACKGROUND: This article reports the 2-year clinical, angiographic, and
      intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared
      with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial.
      METHODS AND RESULTS: This was a prospective, single-blind clinical trial in which
      a total of 300 patients with de novo native coronary artery lesions were
      randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned
      at 2 years in all patients. A subset of 152 patients underwent serial
      angiographic and intravascular ultrasound analyses at 6 months and 2 years. After
      2 years, target lesion failure (cardiac death, myocardial infarction, and
      ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES
      and PES, respectively (P=0.31). At 6 months, a significant reduction in
      angiographic in-stent late loss and percentage volume obstruction measured by
      intravascular ultrasound was observed in the EES group. However, at 2-year follow
      up, a late increased intimal hyperplasia growth after implantation of an EES was
      observed. There were no significant differences between EES and PES for in-stent
      late loss (EES, 0.33+/-0.37 mm versus PES, 0.34+/-0.34 mm; P=0.84) and percentage
      volume obstruction (EES, 5.18+/-6.22% versus PES, 5.80+/-6.31%; P=0.65) at 2
      years. The incidence of stent thrombosis was low and comparable in both groups
      (EES, 0.9%; PES, 1.4%). CONCLUSIONS: Although the previously reported
      angiographic and clinical superiority of the EES has vanished over time, this
      report confirms and extends the previously demonstrated noninferiority in terms
      of in-stent late loss of the EES when compared with the PES up to 2-year follow
      up. There were no significant differences between EES and PES in clinical,
      angiographic and intravascular ultrasound outcomes at 2 years.

PMID- 20031738
TI  - Frequency of allergic or hematologic adverse reactions to ticlopidine among
      patients with allergic or hematologic adverse reactions to clopidogrel.
AB  - BACKGROUND: Clopidogrel and ticlopidine are structurally very similar. In
      patients with an allergic or hematologic adverse reaction to either one of these
      drugs, the likelihood that an allergic or hematologic adverse effect will develop
      to the other is unknown. It is also unknown whether a reaction to the second
      thienopyridine is likely to be life threatening. METHODS AND RESULTS: Medical
      records from 2 academic institutions were reviewed to identify patients who had
      an allergic or hematologic adverse reaction to either of the 2 currently
      commercially available thienopyridines and who were subsequently prescribed the
      other thienopyridine. Patient demographics, details of the adverse reactions, and
      subsequent clinical course were reviewed. A total of 76 patients were identified
      with an allergic or hematologic adverse reaction to clopidogrel or ticlopidine
      who had also received the other thienopyridine. Fourteen (27%; 95% CI, 16 to 41)
      patients who had an allergic or hematologic adverse reactions to clopidogrel had
      a similar reaction to ticlopidine; none developed a life-threatening reaction.
      The most common reaction was a rash (93%). CONCLUSIONS: In patients with an
      allergic or hematologic adverse reaction to one thienopyridine, there seems to be
      an increased frequency of such reactions to the other thienopyridine. However, no
      patient had a life-threatening reaction after exposure to the alternative
      thienopyridine.

PMID- 20031739
TI  - Drug-eluting balloon: the comeback kid?

PMID- 20031741
TI  - Hemodynamic effect of myocardial bridging.

PMID- 20031740
TI  - Intimal dissection causing late thrombosis of a covered stent: optical coherence
      tomography appearances.

PMID- 20031742
TI  - Letter by Alfonso et al regarding article, "Impact of intravascular ultrasound
      guidance on long-term mortality in stenting for unprotected left main coronary
      artery stenosis".

PMID- 20031744
TI  - Superoxygen therapy: a Bayesian breath of fresh air for myocardial salvage.

PMID- 20031746
TI  - Impact of thrombus aspiration on myocardial tissue reperfusion and left
      ventricular functional recovery and remodeling after primary angioplasty.
AB  - BACKGROUND: Failure to achieve myocardial reperfusion often occurs during
      percutaneous coronary intervention (PCI) in patients with myocardial infarction
      with ST-segment elevation. We hypothesized that manual thrombus aspiration during
      primary PCI would favorably influence tissue-level myocardial perfusion and left
      ventricular (LV) functional recovery and remodeling. METHODS AND RESULTS: We
      prospectively randomized 111 patients with ST-segment elevation myocardial
      infarction to either standard or thrombus-aspiration PCI. Primary end point of
      the study was postprocedural incidence of ST-segment resolution >or=70%.
      Secondary end points included Thrombolysis in Myocardial Infarction (TIMI)
      myocardial perfusion grade >or=2, the combination of TIMI myocardial perfusion
      grade >or=2 and ST-segment resolution >or=70%, post-PCI TIMI grade 3 flow,
      corrected TIMI frame count, myocardial contrast echocardiography score index, the
      absence of persistent ST-segment deviation, and time course of wall-motion score
      index, LV ejection fraction, and LV volume in the 2 groups. The incidence of ST
      segment resolution >or=70% was 71% and 39% in the thrombus-aspiration and
      standard PCI groups, respectively (odds ratio, 3.7; 95% CI, 1.7 to 8.3; P=0.001).
      TIMI myocardial perfusion grade >or=2 was attained in 93% in the thrombus
      aspiration group compared with 71% in the standard PCI group (P=0.006). The
      percentage of patients with ST-segment resolution >or=70% and TIMI myocardial
      perfusion grade >or=2 was significantly greater in the thrombus-aspiration group
      compared with the standard PCI group (69% versus 36%, P=0.0006). Myocardial
      contrast echocardiography score index was significantly higher in the thrombus
      aspiration group compared with the standard PCI group (0.86+/-0.20 versus 0.65+/
      0.31; P<0.0001). A significantly greater improvement in LV ejection fraction and
      in wall-motion score index from baseline to 6-month follow-up was observed in the
      thrombus-aspiration group compared with the standard PCI group (LV ejection
      fraction from 48+/-6% to 55+/-6% versus 48.7+/-7% to 49+/-8%, P<0.0001; wall
      motion score index from 1.59+/-0.13 to 1.31+/-0.19 versus 1.64+/-0.20 to 1.51+/
      0.26, P=0.008). Twelve patients (11%) developed LV remodeling at 6 months, 2 (4%)
      in the thrombus-aspiration group and 10 (18%) in the standard PCI group (P=0.02).
      CONCLUSIONS: Manual thrombus aspiration in the setting of primary PCI improves
      myocardial tissue-level perfusion as well as LV functional recovery and
      remodeling.

PMID- 20031745
TI  - Effect of supersaturated oxygen delivery on infarct size after percutaneous
      coronary intervention in acute myocardial infarction.
AB  - BACKGROUND: Myocardial salvage is often suboptimal after percutaneous coronary
      intervention in ST-segment elevation myocardial infarction. Posthoc subgroup
      analysis from a previous trial (AMIHOT I) suggested that intracoronary delivery
      of supersaturated oxygen (SSO(2)) may reduce infarct size in patients with large
      ST-segment elevation myocardial infarction treated early. METHODS AND RESULTS: A
      prospective, multicenter trial was performed in which 301 patients with anterior
      ST-segment elevation myocardial infarction undergoing percutaneous coronary
      intervention within 6 hours of symptom onset were randomized to a 90-minute
      intracoronary SSO(2) infusion in the left anterior descending artery infarct
      territory (n=222) or control (n=79). The primary efficacy measure was infarct
      size in the intention-to-treat population (powered for superiority), and the
      primary safety measure was composite major adverse cardiovascular events at 30
      days in the intention-to-treat and per-protocol populations (powered for
      noninferiority), with Bayesian hierarchical modeling used to allow partial
      pooling of evidence from AMIHOT I. Among 281 randomized patients with tc-99m
      sestamibi single-photon emission computed tomography data in AMIHOT II, median
      (interquartile range) infarct size was 26.5% (8.5%, 44%) with control compared
      with 20% (6%, 37%) after SSO(2). The pooled adjusted infarct size was 25% (7%,
      42%) with control compared with 18.5% (3.5%, 34.5%) after SSO(2)
      (P(Wilcoxon)=0.02; Bayesian posterior probability of superiority, 96.9%). The
      Bayesian pooled 30-day mean (+/-SE) rates of major adverse cardiovascular events
      were 5.0+/-1.4% for control and 5.9+/-1.4% for SSO(2) by intention-to-treat, and
      5.1+/-1.5% for control and 4.7+/-1.5% for SSO(2) by per-protocol analysis
      (posterior probability of noninferiority, 99.5% and 99.9%, respectively).
      CONCLUSIONS: Among patients with anterior ST-segment elevation myocardial
      infarction undergoing percutaneous coronary intervention within 6 hours of
      symptom onset, infusion of SSO(2) into the left anterior descending artery
      infarct territory results in a significant reduction in infarct size with
      noninferior rates of major adverse cardiovascular events at 30 days. Clinical
      Trial Registration- clinicaltrials.gov Identifier: NCT00175058.

PMID- 20031747
TI  - Treatment of acute myocardial infarction with sirolimus-eluting stents results in
      chronic endothelial dysfunction in the infarct-related coronary artery.
AB  - BACKGROUND: Sirolimus-eluting stent (SES) implantation aggravated endothelial
      vasomotor dysfunction in infarct-related coronary arteries. METHODS AND RESULTS:
      This study examined the effect of SES implantation on the duration of reperfusion
      induced endothelial vasomotor dysfunction in infarct-related coronary arteries
      and on postinfarct left ventricular dysfunction in acute myocardial infarction
      (AMI). Patients with a first AMI due to occlusion of the left anterior descending
      coronary artery and successful reperfusion using SES (n=15) or bare metal stents
      (BMS; n=18) were examined. The vasomotor response of the left anterior descending
      coronary artery to acetylcholine and left ventriculography were examined 2 weeks
      and 6 months after AMI. At 6 months after AMI, the impairment of epicardial
      coronary artery dilation and coronary blood flow increase in response to
      acetylcholine was recovered from 2 weeks after AMI in BMS-treated patients,
      whereas the responses of SES-treated patients improved but remained impaired
      compared with BMS-treated patients (% increase in blood flow, 77+/-12% in SES
      versus 116+/-15% in BMS at 10 microg/min of acetylcholine, P<0.01). Left
      ventricular regional wall dysfunction in the left anterior descending coronary
      artery territory improved from 2 weeks to 6 months after AMI in BMS-treated
      patients but not in SES-treated patients (% improvement of average SD/chord, 6%
      in SES versus 19% in BMS, P<0.05), although left ventricular global ejection
      fraction was similar between the groups at any time points. CONCLUSIONS: SES
      implantation may delay recovery of reperfusion-induced endothelial vasomotor
      dysfunction in infarct-related coronary arteries and left ventricular regional
      dysfunction for at least 6 months after AMI.

PMID- 20031748
TI  - Long-term prognosis in an ST-segment elevation myocardial infarction population
      treated with routine primary percutaneous coronary intervention: from clinical
      trial to real-life experience.
AB  - BACKGROUND: We sought to describe the long-term prognosis after routine primary
      percutaneous coronary intervention (pPCI) in a contemporary consecutive
      population of patients with presumed ST-segment elevation myocardial infarction,
      compare it with similar results from the landmark DANAMI-2 trial, and to identify
      a possible impact of time of presentation and referral pattern. METHODS AND
      RESULTS: Long-term prognosis in 1019 presumed ST-segment elevation myocardial
      infarction patients, treated according to modern routine pPCI during the year
      2004, was analyzed and compared with similar data from the DANAMI-2 trial.
      Furthermore, we analyzed the impact of patient presentation to the angioplasty
      center during "off hours" (4 pm to 8 am plus weekends and holidays) and the
      impact of being referred from noninvasive hospitals. At 3 years, 20.4% in the
      routinely treated population versus 19.6% in the DANAMI-2 trial reached the
      combined end point of death, reinfarction, or stroke (P=0.68), whereas the all
      cause mortality was 13.0% and 13.7%, respectively (P=0.65). Patients admitted
      during off hours had the same risk of reaching the combined end point of death,
      reinfarction, or stroke compared with patients admitted during office hours
      (hazards ratio, 1.04; 95% CI, 0.8 to 1.5; P=0.81). Door-to-balloon times of less
      than 90 minutes were achieved in 60% among patients admitted directly to an
      invasive center but only in 40% among transferred patients (P<0.001). Despite
      this difference, no difference in unadjusted or adjusted long-term prognosis was
      found between the 2 groups. CONCLUSIONS: This study shows that ST-segment
      elevation myocardial infarction patients treated with contemporary routine pPCI
      achieve a similar long-term prognosis as patients in the landmark randomized pPCI
      trial (DANAMI-2). Furthermore, the long-term prognosis was the same regardless of
      whether the pPCI was performed during off hours or office hours. Thus, pPCI
      including transportation of patients from noninvasive centers can be applied
      successfully in a real-life population.

PMID- 20031749
TI  - Stent thrombosis in Sweden: a report from the Swedish Coronary Angiography and
      Angioplasty Registry.
AB  - BACKGROUND: The objective was to evaluate the role of risk factors and stent type
      for stent thrombosis (ST) using a large real world registry. METHODS AND RESULTS:
      We evaluated all consecutive coronary stent implantations in Sweden from May 1,
      2005, to June 30, 2007. All cases of ST, documented in the Swedish coronary
      angiography and angioplasty registry until September 21, 2008, were analyzed. ST
      was registered in 882 of 73 798 stents. Acute coronary syndromes, insulin-treated
      diabetes mellitus, smoking, previous coronary intervention, warfarin treatment,
      small stent diameter, and stenting in restenotic, complex, or bypass graft
      lesions had the strongest association with ST in the multivariable statistical
      model. There were considerable differences in the frequency of ST between
      different stent brands. The overall risk of ST was lower in drug-eluting stents
      compared with bare metal stents (adjusted risk ratio, 0.79; 99% CI, 0.63 to
      0.99). However, from 6 months after stent implantation and onward, the risk for
      ST was higher in drug-eluting stents compared with bare metal stents (adjusted
      risk ratio, 2.02; 99% CI, 1.30 to 3.14). CONCLUSIONS: ST is a multifactor
      disease, and the incidence varies considerably between patients based on
      clinical, vessel, and stent characteristics. For drug-eluting stents compared
      with bare metal stents, the risk pattern was biphasic; initially, bare metal
      stents demonstrated a higher risk of ST; whereas after the first months, ST risk
      was higher with drug-eluting stents. Our findings highlight the need for
      prospective randomized studies with head-to-head comparisons between different
      stents.

PMID- 20031750
TI  - Double versus single stenting for coronary bifurcation lesions: a meta-analysis.
AB  - BACKGROUND: Several trials have addressed whether bifurcation lesions require
      stenting of both the main vessel and side branch, but uncertainty remains on the
      benefits of such double versus single stenting of the main vessel only. METHODS
      AND RESULTS: We have conducted a meta-analysis of randomized trials including
      patients with coronary bifurcation lesions who were randomly selected to undergo
      percutaneous coronary intervention by either double or single stenting. Six
      studies (n=1642 patients) were eligible. There was increased risk of myocardial
      infarction with double stenting (risk ratio, 1.78; P=0.001 by fixed effects; risk
      ratio, 1.49 with Bayesian meta-analysis). The summary point estimate suggested
      also an increased risk of stent thrombosis with double stenting, but the
      difference was not nominally significant given the sparse data (risk ratio, 1.85;
      P=0.19). No obvious difference was seen for death (risk ratio, 0.81; P=0.66) and
      target lesion revascularization (risk ratio, 1.09; P=0.67). CONCLUSIONS: Stenting
      of both the main vessel and side branch in bifurcation lesions may increase
      myocardial infarction and stent thrombosis risk compared with stenting of the
      main vessel only.

PMID- 20031751
TI  - Long-term follow-up on a large cohort of "full-metal jacket" percutaneous
      coronary intervention procedures.
AB  - BACKGROUND: Limited long-term data exist on patients who have undergone drug
      eluting stenting of very long lesions (requiring >or=60 mm of continuous stent)
      in native coronary arteries ("full-metal jacket"). METHODS AND RESULTS: We
      examined consecutive procedures taking place between March 2002 and 2007 at 2
      high-volume centers in Milan, Italy. Exclusion criteria were percutaneous
      coronary intervention for restenosis, percutaneous coronary intervention to a
      bypass graft, or percutaneous coronary intervention for acute ST-elevation
      myocardial infarction (MI). We identified 658 full-metal jacket lesions in 617
      patients. Average age of the cohort was 62.0+/-10.6; 32.8% were diabetic, 51.5%
      had a previous MI, and 33.4% had undergone a previous percutaneous transluminal
      coronary angioplasty. Mean ejection fraction was 52.1+/-10.4%. The lesion was a
      chronic total occlusion in 33.0%. Median duration of clinical follow-up was 39
      months (interquartile range, 28 to 50). Six-month follow-up was achieved in 97%
      of patients; 2-year follow-up was achieved in 91%. All-cause mortality rate was
      7.3%; cardiac death rate was 3.6%. Non-procedure-related MI rates were 3.5%.
      Target lesion revascularization rates were 23.4%. There were 17 cases of Academic
      Research Consortium-defined definite or probable stent thrombosis (2.6%): 5
      acute, 2 subacute, 6 late, and 4 very late. Ten of the 17 cases occurred while
      the patient was receiving dual antiplatelet therapy; 4 of the 17 after premature
      termination of 1 or both antiplatelets, and 3 of the 17 occurred while the
      patient was receiving single-antiplatelet therapy, after having completed the
      prescribed course of dual antiplatelet therapy. CONCLUSIONS: When very long
      lesions (>or=60 mm) were treated using overlapping drug-eluting stents, 23.4%
      required a further procedure for restenosis at 3-year follow-up. However, MI,
      stent thrombosis, and cardiac mortality rates were relatively low.

PMID- 20031752
TI  - Significantly improved vascular complications among women undergoing percutaneous
      coronary intervention: a report from the Northern New England Percutaneous
      Coronary Intervention Registry.
AB  - BACKGROUND: Women are at a higher risk for bleeding/vascular complications (VC)
      related to cardiovascular procedures. Although the overall incidence of
      percutaneous coronary intervention (PCI)-related bleeding/VC has declined, the
      impact of this decline, specifically in women, is unknown. METHODS AND RESULTS:
      We studied 13 653 female and 32 334 male consecutive cases, from 2002 to 2007, in
      the Northern New England PCI Registry. We sought to (1) compare absolute rates of
      bleeding/VC in women and men over time, (2) define predictors of bleeding/VC in
      women and men undergoing PCI, and (3) trend the impact of female gender in
      predicting bleeding/VC over time. Bleeding/VC was defined as any access-site
      vessel injury requiring surgical intervention or bleeding requiring transfusion.
      The overall risk of bleeding/VC was significantly higher in women versus men
      (4.5+/-1.3% versus 1.6+/-0.5%; P<0.004). Over time, there was a significant
      (P<0.001) 50% decrease in absolute bleeding/VC rates in both women and men. After
      adjustment for baseline differences, female gender remained a significant
      predictor of increased risk in 2007 (odds ratio, 2.6; 95% CI, 1.74 to 3.91).
      Independent predictors of increased risk of bleeding/VC in women included older
      age, shock, renal failure, presentation with non-ST-elevation myocardial
      infraction and larger sheath sizes, whereas the use of fluoroscopy-guided access,
      closure devices, history of dyslipidemia or prior PCI, and use of bivalirudin
      were protective. CONCLUSIONS: Women undergoing PCI have had a significant decline
      in bleeding/VC rates during the last 6 years. Despite the improvement in
      procedural safety, female gender continues to be associated with a >2-fold risk
      of bleeding/VC compared with men.

PMID- 20031754
TI  - Carotid duplex ultrasound velocity measurements versus intravascular ultrasound
      in detecting carotid in-stent restenosis.
AB  - BACKGROUND: Duplex ultrasonography criteria for assessing the severity of carotid
      artery (CA) in-stent restenosis are not well established. METHODS AND RESULTS: We
      analyzed 39 patients (40 CAs) who underwent CA stenting with baseline and 6-month
      follow-up carotid duplex ultrasonography and intravascular ultrasound.
      Intravascular ultrasound measurements included minimum luminal diameter, percent
      diameter, and lumen area stenosis. Duplex ultrasonography measurements included
      peak systolic velocity (PSV), percentage change in PSV, end-diastolic velocity
      (EDV), and internal-to-common CA PSV ratio (ICA/CCA). Receiver operating
      characteristic curves assessed each duplex measurement to detect >or=50%
      diameter, >or=75% lumen area stenosis, and minimum luminal diameter <3 mm at
      follow-up. At 6-month intravascular ultrasound follow-up, >or=50% diameter and
      >or=75% lumen area CA in-stent restenosis occurred in 20% and 25%, respectively;
      minimum luminal diameter <3 cm occurred in 48%. Area under receiver operating
      characteristic curves for PSV, EDV, and ICA/CCA were 0.85, 0.96, and 0.89 for
      >or=50% diameter stenosis and 0.89, 0.93, and 0.88 for >or=75% lumen area
      stenosis, respectively. Optimal PSV, EDV, and ICA/CCA criteria to detect >or=50%
      diameter and >or=75% lumen area CA in-stent restenosis were greater compared with
      those for native CA. A >98% increase in PSV had the highest specificity, whereas
      the combination of EDV >41 cm/s and ICA/CCA >2 had the highest sensitivity in
      detecting >or=75% lumen area CA in-stent restenosis. CONCLUSIONS: PSV, EDV, and
      ICA/CCA PSV ratio were good discriminators for detecting significant diameter and
      lumen area greater compared with those for native CA. The combination of duplex
      velocity criteria increases diagnostic accuracy.

PMID- 20031753
TI  - Choice of contrast medium in patients with impaired renal function undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: No clinical trial has yet focused on contrast-mediated nephrotoxicity
      in patients with chronic renal failure exclusively undergoing percutaneous
      coronary intervention (PCI). Therefore, the aim of this study was to compare the
      effect of contemporary contrast media on nephrotoxicity in this high-risk patient
      population. METHODS AND RESULTS: This prospective, randomized, double-blind,
      comparative clinical trial randomly selected 939 patients with chronic renal
      failure undergoing coronary angiography with potential PCI to receive either the
      iso-osmolar contrast medium iodixanol or the low-osmolar contrast medium
      iomeprol. Of those 939 patients, 615 received diagnostic angiography only and
      were not included in the primary study analysis, but were followed up in a
      registry. Three hundred twenty-four patients underwent PCI, of which one-half
      received iodixanol or iomeprol, respectively, and were included in the primary
      study analysis. The primary end point was the peak increase in S-creatinine
      during hospitalization for PCI. Maximum increase in S-creatinine after PCI was
      lower than expected and thus impaired the power of the study. It was not
      significantly different between the 2 contrast groups (0.19+/-0.40 mg/dL for
      iodixanol and 0.21+/-0.34 mg/dL for iomeprol; P=0.53). Albeit contrast media
      induced nephropathy rates were lower with iodixanol (22.2% compared with 27.8%
      for iomeprol), this difference was not statistically different (P=0.25). Subgroup
      analysis suggested a favorable outcome regarding nephrotoxicity in patients who
      received higher contrast volumes (>340 mL) in the iodixanol group
      (P(interaction)=0.016). CONCLUSIONS: Routine use of iso-osmolar contrast medium
      is not associated with a significant reduction of nephrotoxicity compared with
      low-osmolar contrast medium in patients with chronic renal failure undergoing
      PCI. However, a positive effect was seen in the iso-osmolar contrast group for
      patients receiving high amounts of contrast medium, which awaits confirmation of
      a specifically designed randomized clinical trial. Clinical Trial Registration-
      clinicaltrials.gov Identifier: NCT00390585.

PMID- 20031755
TI  - Clinical significance of echo signal attenuation on intravascular ultrasound in
      patients with coronary artery disease.
AB  - BACKGROUND: Atherosclerotic plaque that shows echo signal attenuation (EA)
      without associated bright echoes is sometimes observed by intravascular
      ultrasound but its clinical significance remains unclear. We investigated the
      impact of EA on coronary perfusion and evaluated the pathological features of
      plaque with EA. METHODS AND RESULTS: We studied 687 native coronary lesions in
      687 consecutive patients (336 with acute coronary syndrome and 351 with stable
      angina pectoris) who underwent intravascular ultrasound before percutaneous
      coronary intervention. By subgroup analysis, 60 lesions (30 lesions with EA)
      treated with directional coronary atherectomy underwent pathological examination.
      The Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush
      grade after percutaneous coronary intervention were compared between lesions with
      and without EA in 627 lesions except directional coronary atherectomy subgroup.
      EA was observed in 245 lesions (35.7%), and coronary flow after percutaneous
      coronary intervention was worse for lesions with EA than without (final TIMI
      grade of 0 to 2: 15.4% versus 2.4%, P<0.001; final myocardial blush grade of 0 to
      2: 45.6% versus 21.4%, P<0.001). Multivariate analysis revealed a significant
      association between no reflow (TIMI grade 0 to 2) and EA (odds ratio, 5.59; 95%
      CI, 2.64 to 11.85; P<0.001), a baseline TIMI grade of 0 to 2 (odds ratio, 5.91;
      95% CI, 2.79 to 12.5; P<0.001), and a large reference area (odds ratio, 3.08; 95%
      CI, 1.40 to 6.76; P=0.005) after controlling for other associated factors.
      Pathological examination revealed a significantly higher frequency of lipid-rich
      plaque with microcalcification in lesions with EA. CONCLUSIONS: Atherosclerotic
      plaque with EA showed a significant association with no reflow after percutaneous
      coronary intervention, suggesting the existence of fragile components susceptible
      to distal embolization.

PMID- 20031756
TI  - Pulmonary arterial hypertension in patients with transcatheter closure of
      secundum atrial septal defects: a longitudinal study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) may develop in patients with
      atrial septal defects (ASD); however, little is known about associated risk
      factors and its evolution after transcatheter ASD closure. METHODS AND RESULTS:
      We conducted a cohort study on 215 adults with attempted transcatheter ASD
      closure from 1999 to 2006. Patients were classified according to baseline
      systolic pulmonary artery pressures as having no (I, <40 mm Hg), mild (II, 40 to
      49 mm Hg), moderate (III, 50 to 59 mm Hg), or severe (IV, >or=60 mm Hg) PAH.
      Independent predictors of moderate or severe PAH were older age (odds ratio [OR],
      1.10 per year; P<0.0001), larger ASD (OR, 1.13 per millimeter; P=0.0052), female
      sex (OR, 3.9; P=0.0313), and at least moderate tricuspid regurgitation (OR, 3.6;
      P=0.0043). At 15 (interquartile range, 8 to 43) months post-ASD closure, patients
      with higher baseline pressures were more likely to experience a >or=5-mm Hg
      decrease (33.7%, 73.9%, 79.2%, and 100.0% in groups I to IV, P<0.0001), with a
      larger magnitude of reduction (0, 8, 17, and 22 mm Hg; P<0.0001). However,
      normalization of pressures (<40 mm Hg) occurred less frequently in patients with
      more advanced PAH (90.2%, 71.7%, 66.7%, and 23.5%, P<0.0001). Among patients with
      moderate or severe PAH, independent predictors of normalization were lower
      baseline pressures (OR, 0.91 per mm Hg; P=0.0418) and no more than mild tricuspid
      regurgitation (OR, 0.14; P=0.0420). CONCLUSIONS: In adults with ASDs, severity of
      PAH is modulated by age, sex, defect size, and degree of tricuspid regurgitation.
      Patients with moderate or severe PAH may benefit from substantial reductions in
      pulmonary artery pressures after transcatheter ASD closure, although the PAH
      values remain elevated in a sizeable proportion.

PMID- 20031758
TI  - Is patent foramen ovale closure indicated for migraine?: patent foramen ovale
      closure for migraine.

PMID- 20031757
TI  - The SYNTAX trial: a perspective.

PMID- 20031759
TI  - Is patent foramen ovale closure indicated for migraine?: PFO closure is not
      indicated for migraine: "Don't shoot first, ask questions later".

PMID- 20031760
TI  - Advances in intravascular imaging.

PMID- 20031761
TI  - Percutaneous subclavian artery bypass for myocardial perfusion during
      endovascular intervention.

PMID- 20031762
TI  - Letter by Venetucci et al regarding article "Effect of high-dose intracoronary
      adenosine administration during primary percutaneous coronary intervention in
      acute myocardial infarction: a randomized controlled trial".

PMID- 20031764
TI  - Clopidogrel for the hot patient.

PMID- 20031765
TI  - ST-segment-elevation myocardial infarction treated at hospitals with and without
      on-site cardiac surgery: do we have the answer and what about the future?

PMID- 20031766
TI  - The high-risk thin-cap fibroatheroma: a new kid on the block.

PMID- 20031767
TI  - Relationship between baseline inflammatory markers, antiplatelet therapy, and
      adverse cardiac events after percutaneous coronary intervention: an analysis from
      the clopidogrel for the reduction of events during observation trial.
AB  - BACKGROUND: We evaluated patients undergoing percutaneous coronary intervention
      to assess the predictive value of high-sensitivity C-reactive protein (hs-CRP)
      and pregnancy-associated plasma protein-A (PAPP-A) on adverse cardiac outcomes
      and the effect of antiplatelet therapy on these outcomes. METHODS AND RESULTS:
      Baseline blood samples were available on 1468 CREDO (Clopidogrel for the
      Reduction of Events During Observation) patients for hs-CRP testing and 1096
      patients for PAPP-A testing. The 1-year primary end point was the composite
      incidence of death, myocardial infarction, or stroke. Patients in the highest 2
      tertiles of hs-CRP had more events compared with the lowest tertile (11.4% versus
      6.4%, P=0.003). Treatment with clopidogrel reduced the 1-year composite end point
      for patients in the highest 2 tertiles of hs-CRP (9.1% clopidogrel versus 13.5%
      placebo, P=0.04) but not in the lowest tertile. Elevated PAPP-A levels were
      associated with a trend toward more events at 1 year that did not reach
      statistical significance. Patients in the highest 2 tertiles of PAPP-A randomized
      to clopidogrel had fewer events (7.3% clopidogrel versus 13.1% placebo, P=0.01),
      but no benefit was seen in the lowest tertile. A 46% risk reduction with
      randomization to clopidogrel was seen in patients in the highest 2 tertiles of
      both biomarkers (8.7% versus 16.2%, P=0.02). CONCLUSIONS: Patients undergoing
      nonurgent percutaneous coronary intervention who have elevated hs-CRP and PAPP-A
      have an increased incidence of adverse cardiovascular events. The clinical
      benefit of adding clopidogrel to aspirin seems greater in those with increased
      levels of these inflammatory biomarkers.

PMID- 20031768
TI  - Prognostic values of C-reactive protein levels on clinical outcome after
      implantation of sirolimus-eluting stents in patients on hemodialysis.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) using drug-eluting stents
      significantly reduces the risk of restenosis in the general population. However,
      in patients on hemodialysis, adverse cardiac events are frequently seen even if
      treated with drug-eluting stents. Recent studies suggest that C-reactive protein
      (CRP) reflects vascular wall inflammation and can predict adverse cardiac events.
      We evaluated possible prognostic values of CRP on outcomes in patients on
      hemodialysis undergoing PCI with drug-eluting stents. METHODS AND RESULTS: A
      total of 167 patients undergoing PCI with sirolimus-eluting stents for stable
      angina (322 lesions) were enrolled. They were divided into tertiles according to
      serum CRP levels. We analyzed the incidence of major adverse cardiovascular
      events including cardiovascular death, nonfatal myocardial infarction, and target
      lesion revascularization after PCI as well as quantitative coronary angiographic
      data. The mean follow-up was 31 months (SD, 14). Major adverse cardiac events
      occurred in 11 patients (19.6%) of the lowest tertile, in 22 patients (39.3%) of
      the middle tertile, and in 28 patients (50.9%) of the highest tertile during
      follow-up period (P=0.0009). There was a progressive increase in neointimal
      growth after sirolimus-eluting stent implantation during follow-up because
      preprocedural CRP levels were higher, despite similar angiographic data just
      after PCI. Angiographic restenosis at 6 to 8 months after PCI was seen in 10.6%
      in the lowest tertile, 17.9% in the middle tertile, and 32.0% in the highest
      tertile (P=0.0007). CONCLUSIONS: Increased preprocedural serum CRP levels would
      predict higher major adverse cardiac events and restenosis rates after sirolimus
      eluting stents implantation in patients on hemodialysis.

PMID- 20031769
TI  - Outcomes for patients with ST-elevation myocardial infarction in hospitals with
      and without onsite coronary artery bypass graft surgery: the New York State
      experience.
AB  - BACKGROUND: The benefit of primary percutaneous coronary interventions (P-PCI)
      for patients with ST-elevation myocardial infarction (STEMI) has been well
      documented. However, controversy still exists as to whether PCI should be
      expanded to hospitals without coronary artery bypass graft surgery. METHODS AND
      RESULTS: Patients who were discharged after PCI for STEMI between January 1,
      2003, and December 12, 2006, in P-PCI centers (hospitals with no coronary artery
      bypass graft surgery, and PCI only for patients with STEMI) were propensity
      matched with patients in full service centers, and mortality and subsequent
      revascularization rates were compared. For patients undergoing PCI, there were no
      differences for in-hospital/30-day mortality (2.3% for P-PCI centers versus 1.9%
      for full service centers [P=0.40]), emergency coronary artery bypass graft
      surgery immediately after PCI (0.06% versus 0.35%, P=0.06), 3-year mortality
      (7.1% versus 5.9%, P=0.07), or 3-year subsequent revascularization (23.8% versus
      21.5%, P=0.52). P-PCI centers had a lower same/next day coronary artery bypass
      graft rate (0.23% versus 0.69%, P=0.046) and higher repeat target vessel PCI
      rates (12.1% versus 9.0%, P=0.003). For patients with STEMI who did not undergo
      PCI, P-PCI centers had higher in-hospital mortality (28.5% versus 22.3%; adjusted
      odds ratio, 1.38; 95% CI, 1.10 to 1.75). CONCLUSIONS: No differences between P
      PCI centers and full service centers were found in in-hospital/30-day mortality,
      the need for emergency surgery, 3-year mortality or subsequent revascularization,
      but P-PCI centers had higher repeat target vessel PCI rates and higher mortality
      rates for patients who did not undergo PCI. P-PCI centers should be monitored
      closely, including the monitoring of patients with STEMI who did not undergo PCI.

PMID- 20031770
TI  - Prehospital 12-lead ECG to triage ST-elevation myocardial infarction and
      emergency department activation of the infarct team significantly improves door
      to-balloon times: ambulance Victoria and MonashHEART Acute Myocardial Infarction
      (MonAMI) 12-lead ECG project.
AB  - BACKGROUND: American College of Cardiology/American Heart Association guidelines
      recommend >75% of patients with an ST-elevation myocardial infarction receive
      primary percutaneous coronary interventions (PPCI) within 90 minutes. Despite
      these recommendations, this goal has been difficult to achieve. METHODS AND
      RESULTS: We conducted a prospective interventional study involving 349 patients
      undergoing PPCI at a single tertiary referral institution to determine the impact
      of prehospital 12-lead ECG triage and emergency department activation of the
      infarct team on door-to-balloon time (D2BT). The median D2BT of all patients
      (n=107) who underwent PPCI after field ECG and emergency department activation of
      the infarct team (MonashHEART Acute Myocardial Infarction [MonAMI] group) was 56
      minutes (interquartile range, 36.5 to 70) compared with the median time of a
      contemporary group (n=122) undergoing PPCI during the same period but not
      receiving field triage (non-MonAMI group) of 98 minutes (73 to 126.45). The
      median D2BT time of 120 consecutive patients who underwent PPCI before initiation
      of the project (pre-MonAMI group) was 101.5 minutes (72.5 to 134; P<0.001). The
      proportion of patients who achieved a D2BT of < or = 90 minutes increased from
      39% in the pre-MonAMI group and 45% in the non-MonAMI group to 93% in the MonAMI
      group (P<0.001). CONCLUSIONS: The performance of prehospital 12-lead ECG triage
      and emergency department activation of the infarct team significantly improves
      D2BT and results in a greater proportion of patients achieving guideline
      recommendations.

PMID- 20031771
TI  - Interventional therapy of bifurcation lesions: a TIMI flow-guided concept to
      treat side branches in bifurcation lesions--a prospective randomized clinical
      study (Thueringer bifurcation study, THUEBIS study as pilot trial).
AB  - BACKGROUND: Treatment of bifurcations is a complex problem. The clinical value of
      treating side branches is an unsolved problem in the field of interventional
      cardiology. METHODS AND RESULTS: We initiated a prospective randomized controlled
      trial. One hundred and ten patients with bifurcations were randomly assigned to 2
      arms: Stenting of the main branch (MB, Taxus-stent, paclitaxel-eluting stents)
      and mandatory side branch (SB) percutaneous coronary intervention (PCI; kissing
      balloons) with provisional SB stenting (therapy A), or stenting of the MB
      (paclitaxel-eluting stents) with provisional SB-PCI only when the SB had a
      thrombolysis in myocardial infarction flow <2 (therapy B). The primary end point
      was target lesion revascularization. The mean ages were 66.8 years (A) versus
      65.1 years (B, P=0.4), 71.4% (A) versus 77.8% were men (P=0.4), patients with
      diabetes were present in 25.0% versus 25.9% (P=0.9). The MB was left anterior
      descending artery in 80.4% versus 81.5% (A versus B, P=0.9). The SB-PCI and
      kissing balloon-PCI were performed according to the study protocol in 82.1%/73.2%
      versus 16.7%/13.0% (P<0.05 for both), while changing of the intended therapy was
      necessary in 17.9% versus 16.7% (A versus B, P=0.9). A final thrombolysis in
      myocardial infarction flow 3 (MB) was reached in all patients (groups A and B),
      final thrombolysis in myocardial infarction flow 3 (SB) was observed in 96.4%
      versus 88.9% (A versus B, P=0.3). Radiation time (min) and contrast medium (mL)
      were 14.2/210 (group A) versus 7.8/151.6 (group B; P for both <0.05). Six month -
      follow up: major adverse cardiac events was 23.2% (A) versus 24.1% (B, P=0.9),
      target lesion revascularization was 17.9% (A) versus 14.8% (B, P=0.7), and late
      lumen loss (MB) was 0.2 mm (A) versus 0.3 mm (B, P=0.5). In group B, no PCI of
      the SB was done during follow up. CONCLUSIONS: A simple strategy using paclitaxel
      eluting stents with only provisional SB-PCI may be of equal value to a more
      complex strategy with mandatory SB-PCI. Clinical Trial Registration- URL:
      http://www.controlled.trials.com. Unique identifier: ISRCTN22637771.

PMID- 20031772
TI  - Diabetes duration is associated with increased thin-cap fibroatheroma detected by
      intravascular ultrasound with virtual histology.
AB  - BACKGROUND: Coronary plaque classified as thin-cap fibroatheroma (TCFA) is
      believed to be associated with plaque rupture and coronary heart disease-related
      events. Although an association between duration of diabetes and increased
      coronary heart disease risk has been demonstrated, the relationship between TCFA
      and diabetes duration is unknown. METHODS AND RESULTS: Prospective registry of
      diabetic patients undergoing diagnostic coronary angiography and intravascular
      ultrasound (IVUS) enrolled in a diabetic gene and biomarker banking registry.
      Plaque composition in the most diseased 10-mm segment of a single coronary artery
      was assessed using IVUS virtual histology and was classified by phenotype as IVUS
      defined adaptive intimal thickening, pathological intimal thickening, TCFA,
      fibroatheroma, or fibrocalcific. Patients (n=54) were stratified by duration of
      diabetes (<10 or > or = 10 years). Patients with diabetes > or = 10 years were
      older, less likely to have a history of tobacco use, had higher total cholesterol
      levels, and were more likely to be treated with insulin compared with patients
      with diabetes <10 years. Longer duration of diabetes was associated with greater
      plaque burden in the most diseased 10-mm segment (60.4% [53.4% to 66.8%] versus
      50.2% [47.7% to 58.4%], P=0.008). The proportion of IVUS-defined TCFA in the > or
      = 10-year group was greater than the <10-year group (54.4% [11.6% to 77.5%]
      versus 10.8% [0.0% to 26.1%], P=0.009). This association persisted after
      adjustment for multiple comparisons, clinical characteristics, and diabetes
      treatment. CONCLUSIONS: In this cohort, longer duration of diabetes was
      associated with IVUS-defined TCFA, a plaque phenotype associated with risk of
      rupture and coronary heart disease events. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00428961.

PMID- 20031773
TI  - Vascular closure device failure: frequency and implications: a propensity-matched
      analysis.
AB  - BACKGROUND: Vascular closure devices (VCDs) are effective in reducing the time to
      ambulation for patients undergoing cardiac catheterization procedures and in
      reducing the risk of vascular complications in selected patient cohorts. However,
      the frequency and consequence of failure of VCDs is not well defined. METHODS AND
      RESULTS: From a prospective registry of consecutive patients undergoing cardiac
      catheterization at our center, 9823 patients who received either a collagen plug
      based (Angio-Seal) or a suture-based (Perclose) VCD were selected for the study.
      VCD failure was defined as unsuccessful deployment or failure to achieve
      hemostasis. Major vascular complication was defined as any retroperitoneal
      hemorrhage, limb ischemia, or any surgical repair. Minor vascular complication
      was defined as any groin bleeding, hematoma (> or = 5 cm), pseudoaneurysm, or
      arteriovenous fistula. Any vascular complication was defined as either a major or
      minor vascular complication. Among the 9823 patients in the study, VCD failed in
      268 patients (2.7%; 2.3% diagnostic versus 3.0% percutaneous coronary
      intervention; P=0.029). Patients with VCD failure had significantly increased
      risk of any (6.7% versus 1.4%; P<0.0001), major (1.9% versus 0.6%; P=0.006), or
      minor (6.0% versus 1.1%; P<0.0001) vascular complication compared with the group
      with successful deployment of VCD. The increased risk of vascular complication
      was unchanged in a propensity score-matched cohort. CONCLUSIONS: In contemporary
      practice, VCD failure is rare, but when it does fail, it is associated with a
      significant increase in the risk of vascular complications. Patients with VCD
      failure should be closely monitored.

PMID- 20031774
TI  - Insight into the dynamics of the coronary sinus/great cardiac vein and the mitral
      annulus: implications for percutaneous mitral annuloplasty techniques.
AB  - BACKGROUND: Implantation of devices into the coronary sinus (CS)/great cardiac
      vein (GCV) to reshape the mitral annulus (MA) is being investigated, despite
      these structures not being within the same plane and coronary arteries frequently
      traversing between them. Furthermore, dynamic changes in their relationship have
      never been studied. We analyzed the CS/GCV dimensions and its relationship with
      the MA and the coronary arteries. METHODS AND RESULTS: Of 390 consecutive
      computed tomography angiographies reviewed, 56 met the inclusion criteria. Mean
      age of the patients was 68.9 + or - 13.1 years (26.8% men). The dimensions of the
      CS/GCV and the distance between this structure and the MA were measured at 10
      different spatial points along the CS/GCV trajectory and at 3 different time
      points along the cardiac cycle (phases 0%, 40%, and 75% of the RR interval) by
      using curved multiplanar reconstruction technique. The CS/GCV was larger in phase
      40% than in phase 75% and was smallest in phase 0% (P<0.001). The distance
      between the CS/GCV and the MA was longest in phase 40% and shortest in phase 0%
      (P=0.013). The diameter of the MA was measured in oblique 2- and 4-chamber
      reconstructions, being largest in phase 0% and smallest in phase 40% (P=0.019). A
      coronary artery traversed between the CS/GCV and the MA in 85.7% of the patients.
      CONCLUSIONS: This study demonstrated dynamic changes in the relationship between
      the CS/GCV and the MA and also that coronary arteries frequently traverse between
      both structures. Whether these findings are of clinical relevance for patients
      undergoing percutaneous mitral annuloplasty needs to be prospectively evaluated.

PMID- 20031775
TI  - Interventional cardiology perspective of functional tricuspid regurgitation.

PMID- 20031776
TI  - Percutaneous coronary intervention in perspective: drug-eluting stents as a model
      for regulatory review.

PMID- 20031777
TI  - Retroperitoneal hematoma after diagnostic coronary angiography caused by
      collateralization of a chronic common femoral artery occlusion secondary to
      childhood femoral cannulation.

PMID- 20031778
TI  - Perforation of the membranous interventricular septum after transcatheter aortic
      valve implantation.

PMID- 20031779
TI  - Circulation: cardiovascular quality and outcomes: scholarship to improve health
      and health care for patients and populations.

PMID- 20031780
TI  - When is better not good enough?: Insights from the COURAGE economic study.

PMID- 20031781
TI  - Informing the consent process.

PMID- 20031782
TI  - Measuring quality in heart failure: do we have the metrics?

PMID- 20031783
TI  - Cost-effectiveness of percutaneous coronary intervention in optimally treated
      stable coronary patients.
AB  - BACKGROUND: The COURAGE (Clinical Outcomes Utilizing Revascularization and
      Aggressive druG Evaluations) trial compared the effect of percutaneous coronary
      intervention (PCI) plus optimal medical therapy with optimal medical therapy
      alone on cardiovascular events in 2287 patients with stable coronary disease.
      After 4.6 years, there was no difference in the primary end point of death or
      myocardial infarction, although PCI improved quality of life. The present study
      evaluated the relative cost and cost-effectiveness of PCI in the COURAGE trial.
      METHODS AND RESULTS: Resource use was assessed by diagnosis-related group for
      hospitalizations and by current procedural terminology code for outpatient visits
      and tests and then converted to costs by use of 2004 Medicare payments.
      Medication costs were assessed with the Red Book average wholesale price. Life
      expectancy beyond the trial was estimated from Framingham survival data.
      Utilities were assessed by the standard gamble method. The incremental cost
      effectiveness ratio was expressed as cost per life-year and cost per quality
      adjusted life-year gained. The added cost of PCI was approximately $10,000,
      without significant gain in life-years or quality-adjusted life-years. The
      incremental cost-effectiveness ratio varied from just over $168,000 to just under
      $300,000 per life-year or quality-adjusted life-year gained with PCI. A large
      minority of the distributions found that medical therapy alone offered better
      outcome at lower cost. The costs per patient for a significant improvement in
      angina frequency, physical limitation, and quality of life were $154,580,
      $112,876, and $124,233, respectively. CONCLUSIONS: The COURAGE trial did not find
      the addition of PCI to optimal medical therapy to be a cost-effective initial
      management strategy for symptomatic, chronic coronary artery disease.

PMID- 20031784
TI  - Converting the informed consent from a perfunctory process to an evidence-based
      foundation for patient decision making.
AB  - BACKGROUND: Standard consent forms result in highly variable communication
      between patients and physicians. To enhance the consent process and facilitate
      shared decision making, we developed a World Wide Web-based program, PREDICT
      (Patient Refined Expectations for Deciding Invasive Cardiac Treatments), to
      systematically embed patient-specific estimates of death, bleeding, and
      restenosis into individualized percutaneous coronary intervention informed
      consent documents. We then compared patients' experiences with informed consent
      before and after implementation of PREDICT. METHODS AND RESULTS: Between August
      2006 and May 2007, patients undergoing nonemergent cardiac catheterization who
      received the original consent form (n=142) were interviewed and compared with
      those who received the PREDICT consent form (n=193). Hierarchical modified
      Poisson regression models were used to adjust for clustering of patients within
      physicians. Compared with the original consent group, those in the PREDICT group
      reported higher rates of reading the consent form (72% versus 44%, relative risk
      [RR] 1.64, 95% confidence interval [CI] 1.24 to 2.16), increased perception of
      shared decision making (67% versus 45%, RR 1.48, 95% CI 0.99 to 2.22), and
      decreased anxiety (35% versus 55%, RR 0.70, 95% CI 0.53 to 0.91). Although there
      were no differences between groups in patients' ability to name complications of
      percutaneous coronary intervention, among patients who identified either death or
      bleeding as a potential complication, more patients in the PREDICT group recalled
      being informed of their estimated risk of that complication (death: 85% versus
      62%, RR 1.37, 95% CI 1.03 to 1.82; bleeding: 92% versus 71%, RR 1.28, 95% CI 1.06
      to 1.56). CONCLUSIONS: In this preliminary, single-center experience,
      individualized consent forms with patient-specific risks were associated with
      improved participation in the consent process, reduced anxiety, and better risk
      recall. PREDICT is one potential strategy for improving the current practice of
      obtaining informed consent for percutaneous coronary intervention.

PMID- 20031785
TI  - An administrative claims measure suitable for profiling hospital performance on
      the basis of 30-day all-cause readmission rates among patients with heart
      failure.
AB  - BACKGROUND: Readmission soon after hospital discharge is an expensive and often
      preventable event for patients with heart failure. We present a model approved by
      the National Quality Forum for the purpose of public reporting of hospital-level
      readmission rates by the Centers for Medicare & Medicaid Services. METHODS AND
      RESULTS: We developed a hierarchical logistic regression model to calculate
      hospital risk-standardized 30-day all-cause readmission rates for patients
      hospitalized with heart failure. The model was derived with the use of Medicare
      claims data for a 2004 cohort and validated with the use of claims and medical
      record data. The unadjusted readmission rate was 23.6%. The final model included
      37 variables, had discrimination ranging from 15% observed 30-day readmission
      rate in the lowest predictive decile to 37% in the upper decile, and had a c
      statistic of 0.60. The 25th and 75th percentiles of the risk-standardized
      readmission rates across 4669 hospitals were 23.1% and 24.0%, with 5th and 95th
      percentiles of 22.2% and 25.1%, respectively. The odds of all-cause readmission
      for a hospital 1 standard deviation above average was 1.30 times that of a
      hospital 1 standard deviation below average. State-level adjusted readmission
      rates developed with the use of the claims model are similar to rates produced
      for the same cohort with the use of a medical record model (correlation, 0.97;
      median difference, 0.06 percentage points). CONCLUSIONS: This claims-based model
      of hospital risk-standardized readmission rates for heart failure patients
      produces estimates that may serve as surrogates for those derived from a medical
      record model.

PMID- 20031786
TI  - One-year costs in patients with a history of or at risk for atherothrombosis in
      the United States.
AB  - BACKGROUND: Atherothrombosis is the underlying cause of cardiovascular,
      cerebrovascular, and peripheral arterial disease and is the leading cause of
      death in the industrialized world. The objectives of the present study are (1) to
      examine the annual costs associated with vascular events and interventions that
      require hospitalization, as well as long-term medication use for the management
      of associated risk factors, in a US population of outpatients with multiple
      atherothrombotic risk factors or a history of symptomatic disease and (2) to
      compare costs across patient subgroups defined according to specific arterial
      bed(s) affected and the number of affected arterial beds. METHODS AND RESULTS:
      The international REduction of Atherothrombosis for Continued Health (REACH)
      Registry enrolled outpatients > or =45 years of age who had established coronary
      artery, cerebrovascular, or peripheral artery disease or > or =3 atherothrombotic
      risk factors. Data on risk factors, associated medications, and vascular
      hospitalizations and interventions were collected. Of the total 68 236-patient
      REACH cohort, 25 763 were enrolled from US sites. Complete 1-year data were
      available for 23 974 (93%) of the US patients. Annualized medication costs ranged
      from $2401 to $3481. Mean annual hospitalization costs per patient were $1344,
      $2864, $4824, and $8155 for patients with 0 (n=6145), 1 (n=14 353), 2 (n=3106),
      and 3 (n=370) affected arterial beds at baseline (P<0.0001 for trend). Among
      patients with 1 affected arterial bed, mean hospitalization costs were $2999,
      $2010, and $3911 for patients with coronary artery disease (n=11 063),
      cerebrovascular disease (n=2613), and peripheral arterial disease (n=677),
      respectively. Annualized medication costs ranged from $2401 to $3481.
      CONCLUSIONS: These results reveal the high economic burden of atherothrombosis
      related clinical events and procedures and the especially high economic burden
      associated with polyvascular disease.

PMID- 20031787
TI  - Prevalence, awareness, treatment, and predictors of control of hypertension in
      New York City.
AB  - BACKGROUND: Hypertension-related risk in urban areas may vary from national
      estimates; however, objective data on prevalence and treatment in local areas are
      scarce. We assessed hypertension prevalence, awareness, treatment, and control
      among New York City (NYC) adults. METHODS AND RESULTS: The NYC Health And
      Nutrition Examination Survey (HANES), modeled on the national HANES, was
      conducted in 2004 with a representative sample of noninstitutionalized NYC
      residents > or =20 years of age. Hypertension outcomes were examined with
      interview and examination data (n=1975). Multiple logistic regression was used to
      assess factors associated with control among adults with hypertension. We found
      that 25.6% of NYC adults had hypertension. Blacks had a higher prevalence than
      whites (32.8% versus 21.1%, P<0.001), as did Hispanics (26.5% versus 21.1%,
      P<0.05). Foreign-born residents who had lived in the United States for <10 years
      had lower rates than those who had lived in the United States longer (20.0%
      versus 27.5%, P<0.05). Among adults with hypertension, 83.0% were diagnosed,
      72.7% were treated, and 47.1% had hypertension controlled. Of those treated,
      64.8% had hypertension controlled. After adjustment for sociodemographic
      variables among all adults with treated hypertension, lack of a routine place of
      medical care was most strongly associated with poor control levels (adjusted odds
      ratio 0.21, 95% confidence interval 0.07 to 0.66). Among nonelderly adults with
      treated hypertension, blacks had 4-fold lower odds than whites of having
      hypertension controlled (adjusted odds ratio 0.24, 95% confidence interval 0.06
      to 0.92). CONCLUSIONS: In NYC, hypertension is common and frequently
      uncontrolled. Low levels of control are associated with poor access to care.
      Racial disparities in prevalence and control are evident among nonelderly adults.

PMID- 20031788
TI  - Preliminary observations from preliminary trial results: have we finally had
      enough?

PMID- 20031789
TI  - Changing the practice of perioperative cardioprotection: perioperative beta
      blockers after POISE (PeriOperative ISchemic Evaluation).

PMID- 20031790
TI  - Primer on statistical interpretation or methods report card on propensity-score
      matching in the cardiology literature from 2004 to 2006: a systematic review.
AB  - BACKGROUND: Propensity-score matching is frequently used in the cardiology
      literature. Recent systematic reviews have found that this method is, in general,
      poorly implemented in the medical literature. The study objective was to examine
      the quality of the implementation of propensity-score matching in the general
      cardiology literature. METHODS AND RESULTS: A total of 44 articles published in
      the American Heart Journal, the American Journal of Cardiology, Circulation, the
      European Heart Journal, Heart, the International Journal of Cardiology, and the
      Journal of the American College of Cardiology between January 1, 2004, and
      December 31, 2006, were examined. Twenty of the 44 studies did not provide
      adequate information on how the propensity-score-matched pairs were formed.
      Fourteen studies did not report whether matching on the propensity score balanced
      baseline characteristics between treated and untreated subjects in the matched
      sample. Only 4 studies explicitly used statistical methods appropriate for
      matched studies to compare baseline characteristics between treated and untreated
      subjects. Only 11 (25%) of the 44 studies explicitly used statistical methods
      appropriate for the analysis of matched data when estimating the effect of
      treatment on the outcomes. Only 2 studies described the matching method used,
      assessed balance in baseline covariates by appropriate methods, and used
      appropriate statistical methods to estimate the treatment effect and its
      significance. CONCLUSIONS: Application of propensity-score matching was poor in
      the cardiology literature. Suggestions for improving the reporting and analysis
      of studies that use propensity-score matching are provided.

PMID- 20031791
TI  - Pharmacotherapy for pediatric cardiovascular diseases: the role of off-label drug
      use in the 21st century.

PMID- 20031792
TI  - Anticoagulation control in atrial fibrillation: optimizing risks and benefits.

PMID- 20031793
TI  - Off-label use of cardiovascular medications in children hospitalized with
      congenital and acquired heart disease.
AB  - BACKGROUND: Many barriers exist to conducting pediatric cardiovascular (CV)
      trials, and the majority of therapies used are not evidence based. Recent
      legislation has aimed to stimulate pediatric research and improve drug labeling.
      This study describes off-label use of CV medications in children hospitalized
      with congenital and acquired CV disease. METHODS AND RESULTS: The 2005 Pediatric
      Health Information System database was queried for patients with CV International
      Classification of Disease, Ninth Revision codes who received CV medications. Off
      label use (patient younger than US Food and Drug Administration-approved age) was
      described. Multivariate analysis used Poisson regression to model the number of
      CV drugs received off-label. There were 31,432 patients included (median age,
      10.4 months; interquartile range, 30 days to 6.8 years). Congenital heart disease
      (67%) was the most common diagnosis. Other diagnoses included hypertension,
      arrhythmia, myocarditis/cardiomyopathy, pulmonary hypertension, rheumatic
      fever/endocarditis, and heart transplant. Seventy-eight percent received > or = 1
      CV medication off-label, and 31% received > or = 3 CV medications off-label. The
      most commonly used CV medications were furosemide, epinephrine, dopamine,
      lidocaine, and milrinone. The latter 3 (prescribed in 69% of patients) were used
      off-label in all cases. Medications studied under recent federal initiatives were
      prescribed in only 20% of patients, and were still used off-label 62% of the
      time. In multivariate analysis, heart transplant recipients (odds ratio 1.7; 95%
      CI 1.5 to 1.9) were most likely to receive a greater number of off-label CV
      medications. CONCLUSIONS: Despite recent legislation, off-label use of CV
      medications in the pediatric population is common. These data highlight the need
      for further study to determine which treatments should be used more frequently
      and which are unsafe or ineffective in children hospitalized with CV disease.

PMID- 20031794
TI  - Anticoagulation control and prediction of adverse events in patients with atrial
      fibrillation: a systematic review.
AB  - BACKGROUND: To date, there has been no systematic examination of the relationship
      between international normalized ratio (INR) control measurements and the
      prediction of adverse events in patients with atrial fibrillation on oral
      anticoagulation. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and Cochrane
      through January 2008 for studies of atrial fibrillation patients receiving
      vitamin-K antagonists that reported INR control measures (percentage of time in
      therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and
      thromboembolic events. In total, 47 studies were included from 38 published
      articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%.
      From studies reporting both measures, TTR significantly correlated with
      percentage of INRs in range (P<0.001). Randomized controlled trials had better
      INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR
      negatively correlated with major hemorrhage (r=-0.59; P=0.002) and thromboembolic
      rates (r=-0.59; P=0.01). This effect was significant in retrospective studies
      (major hemorrhage, r=-0.78; P=0.006 and thromboembolic rate, r=-0.88; P=0.03) but
      not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and
      thromboembolic rate, r=-0.61; P=0.07). For retrospective studies, a 6.9%
      improvement in the TTR significantly reduced major hemorrhage by 1 event per 100
      patient-years of treatment (95% CI, 0.29 to 1.71 events). CONCLUSIONS: In atrial
      fibrillation patients receiving orally administered anticoagulation treatment,
      TTR and percentage of INRs in range effectively predict INR control. Data from
      retrospective studies support the use of TTR to accurately predict reductions in
      adverse events.

PMID- 20031795
TI  - C-reactive protein and reclassification of cardiovascular risk in the Framingham
      Heart Study.
AB  - BACKGROUND: The relationship of circulating levels of high-sensitivity C-reactive
      protein (CRP) with cardiovascular disease (CVD) risk, particularly with
      consideration of effects at intermediate levels of risk, has not been fully
      assessed. METHODS AND RESULTS: Among 3006 offspring participants in the
      Framingham Heart Study free of CVD (mean age, 46 years at baseline), there were
      129 hard coronary heart disease (CHD) events and 286 total CVD events during 12
      years of follow-up. Cox regression, discrimination with area under the receiver
      operating characteristic curve, and net reclassification improvement were used to
      assess the role of CRP on vascular risk. In an age-adjusted model that included
      both sexes, the hazard ratios for new hard CHD and total CVD were significantly
      associated with higher CRP levels. Similar analyses according to increasing
      homocysteine level showed significant protective associations for hard CHD but
      not for total CVD. In multivariable analyses that included age, sex, systolic
      blood pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes
      mellitus, current smoking, hypertension treatment, and homocysteine, the log CRP
      level remained significantly related to development of hard CHD and total CVD and
      provided moderate improvement in the discrimination of events. The net
      reclassification improvement when CRP was added to traditional factors was 5.6%
      for total CVD (P=0.014) and 11.8% for hard CHD (P=0.009). CONCLUSIONS:
      Circulating levels of CRP help to estimate risk for initial cardiovascular events
      and may be used most effectively in persons at intermediate risk for vascular
      events, offering moderate improvement in reclassification of risk.

PMID- 20031796
TI  - A novel family-based intervention trial to improve heart health: FIT Heart:
      results of a randomized controlled trial.
AB  - BACKGROUND: Family members of patients with cardiovascular disease (CVD) may be
      at increased risk due to shared genes and lifestyle. Hospitalization of a family
      member with CVD may represent a "motivational moment" to take preventive action.
      METHODS AND RESULTS: A randomized, controlled clinical trial was conducted in
      healthy adult family members (N=501; 66% female; 36% nonwhite; mean age, 48
      years) of patients hospitalized with CVD to evaluate a special intervention (SI)
      with personalized risk factor screening, therapeutic lifestyle-change counseling,
      and progress reports to physicians versus a control intervention (CIN) on the
      primary outcome, mean percent change in low-density lipoprotein cholesterol (LDL
      C), and other risk factors. Validated dietary assessments and standardized risk
      factors were obtained at baseline and 1 year (94% follow-up). At baseline, for
      93% of subjects, saturated fat comprised > or = 7% of total caloric intake, and
      79% had nonoptimal LDL-C levels (of which 50% were unaware). There was no
      difference in the SI versus the CIN with respect to the mean percent change in
      LDL-C (-1% versus -2%, respectively; P=0.64), owing to a similar significant
      reduction in LDL-C in both groups (-4.4 mg/dL and -4.5 mg/dL, respectively). Diet
      score significantly improved in the SI versus the CIN (P=0.04). High-density
      lipoprotein cholesterol declined significantly in the CIN but not in the SI (
      3.2% [95% CI, -5.1 to -1.3] versus +0.3% [95% CI, -1.7 to +2.4]; P=0.01). At 1
      year, SI subjects were more likely than controls to exercise >3 days per week
      (P=0.04). CONCLUSIONS: The SI was not more effective than the CIN in reducing the
      primary end point, LDL-C. The screening process identified many family members of
      hospitalized patients with CVD who were unaware of their risk factors, and
      further work is needed to develop and test interventions to reduce their CVD
      risk.

PMID- 20031797
TI  - Effects of ranolazine on disease-specific health status and quality of life among
      patients with acute coronary syndromes: results from the MERLIN-TIMI 36
      randomized trial.
AB  - BACKGROUND: Ranolazine has been shown to reduce myocardial ischemia and symptom
      severity among selected patients with chronic angina. However, data regarding the
      effect of ranolazine on health status/quality of life (QOL) are limited. METHODS
      AND RESULTS: We performed a prospective QOL analysis alongside the Metabolic
      Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary
      syndromes (MERLIN)-TIMI 36 trial, a randomized, double-blind, placebo-controlled
      trial of ranolazine in 6560 patients with non-ST-elevation acute coronary
      syndromes. Health status/QOL was evaluated at baseline and 4, 8, and 12 months
      after index hospitalization using the Seattle Angina Questionnaire, Rose dyspnea
      scale, SF-12, and EuroQol-5D. Health status/QOL scores improved significantly at
      all follow-up time points for both treatment arms. In the overall population,
      randomization to ranolazine was associated with minimal 12-month improvements in
      angina frequency and Seattle Angina Questionnaire-QOL (P<0.05). In subsequent
      exploratory analyses, there was a significant interaction between the benefits of
      ranolazine and anginal status before the index event. Among patients with prior
      angina (n=3565), treatment with ranolazine was associated with modest benefits
      across the full range of QOL domains, with the greatest benefits observed in
      angina frequency (mean effect=3.4; P<0.001) and Seattle Angina Questionnaire-QOL
      (mean effect=2.7; P<0.001). There were no significant benefits among patients
      without prior angina, however. CONCLUSIONS: Among a broad population of patients
      with unstable coronary disease, ranolazine had a minimal effect on disease
      specific health status and QOL over approximately 12 months of follow-up. Posthoc
      subgroup analysis, however, suggested a modest benefit among the subgroup of
      patients with angina before their acute coronary syndromes event.

PMID- 20031799
TI  - Sex and gender discrepancies in health-related quality of life outcomes among
      patients with established coronary artery disease.
AB  - BACKGROUND: Although eradicating discrepancies in health is of unquestioned
      importance, there are few studies examining health-related quality of life
      (HRQOL) among men and women with coronary artery disease (CAD), a highly
      prevalent and morbid condition among industrialized nations. This study compares
      the HRQOL outcomes of men and women in Alberta, Canada, 1 year after the
      documentation of coronary artery disease by cardiac catheterization. METHOD AND
      RESULTS: Patients' disease-specific HRQOL was assessed 1 year after angiography
      using the Seattle Angina Questionnaire, whereas their generic health status,
      burden of depressive symptoms, and social support were respectively quantified
      with the EuroQol EQ-5D, the Center for Epidemiological Studies Depression Scale
      (short form), and the Medical Outcomes Study social support scale. The latter 2
      instruments were used to adjust Seattle Angina Questionnaire outcomes for
      potential confounding characteristics hypothesized to be associated with sex and
      gender. General linear modeling and a change in Seattle Angina Questionnaire
      scores from baseline to 1 year were used to compare the HRQOL outcomes of men and
      women, after adjusting for demographics, clinical factors, depressive symptoms,
      and social support differences between groups. A total of 2394 (60% of those
      eligible) patients responded to the baseline and the 1-year follow-up survey. The
      adjusted mean 1-year Seattle Angina Questionnaire scores were significantly
      higher in men when compared with women, even after adjustment for all clinical
      factors, social support, depressive symptoms, and baseline HRQOL scales. Not only
      were women noted to have worse health status at the time of angiography, but
      despite adjusting for these differences, residual discrepancies in 1-year health
      status persisted. CONCLUSIONS: Women with coronary artery disease report worse
      HRQOL 1 year after coronary angiography when compared with men, and the
      discrepancies observed are only partially accounted for by sex differences in
      depression and social support. As a result, the measurement of gender roles and
      perceptions may be the best place to persist on the quest to identifying and
      understanding the noted discrepancies in cardiac recovery and HRQOL outcomes.

PMID- 20031798
TI  - Coronary revascularization at specialty cardiac hospitals and peer general
      hospitals in black Medicare beneficiaries.
AB  - BACKGROUND: Critics have raised concerns that specialty cardiac hospitals
      exacerbate racial disparities in cardiovascular care, but empirical data are
      limited. METHODS AND RESULTS: We used administrative data from the Medicare
      Provider and Analysis Review Part A and Provider-of-Service files from 2002 to
      2005. Multivariable logistic regression models were constructed to examine the
      likelihood of black Medicare patients being admitted to a cardiac hospital for
      coronary revascularization when compared with white patients within the same
      healthcare referral region after accounting for geographic proximity to the
      nearest hospitals, procedural acuity, and comorbidities. We identified 35 309
      patients who underwent coronary artery bypass grafting in 18 healthcare referral
      regions and 94,525 patients who underwent percutaneous coronary intervention in
      20 healthcare referral regions where cardiac hospitals performed these
      procedures. Patients at cardiac hospitals were more likely to be men and white
      and have less comorbidity than those at general hospitals. The likelihood of
      black patients undergoing coronary revascularization at a cardiac hospital was
      significantly lower for coronary artery bypass grafting (adjusted odds ratio,
      0.67; P=0.01) and percutaneous coronary intervention (adjusted odds ratio, 0.63;
      P<0.0001). However, this relationship was substantially attenuated among black
      patients living in close proximity (ie, within 10 miles) to cardiac hospitals
      (adjusted odds ratio for coronary artery bypass grafting, 0.95; P=0.75; adjusted
      odds ratio for percutaneous coronary intervention, 0.78; P=0.01). CONCLUSIONS:
      Black patients were significantly less likely to be admitted at cardiac hospitals
      for coronary revascularization. Precise reasons for these findings are unclear
      but suggest complex associations between race and geography in decisions about
      where to receive care.

PMID- 20031800
TI  - Prevention of future cardiovascular disease in high-risk pediatric patients: a
      role for lipid lowering therapy?

PMID- 20031801
TI  - Reexamining the emperor's new clothes: ambiguities in current cardiac screening
      recommendations for youth with attention deficit hyperactivity disorder.

PMID- 20031802
TI  - The Cardiovascular Research Network: a new paradigm for cardiovascular quality
      and outcomes research.
AB  - BACKGROUND: A clear need exists for a more systematic understanding of the
      epidemiology, diagnosis, and management of cardiovascular diseases. More robust
      data are also needed on how well clinical trials are translated into contemporary
      community practice and the associated resource use, costs, and outcomes. METHODS
      AND RESULTS: The National Heart, Lung, and Blood Institute recently established
      the Cardiovascular Research Network, which represents a new paradigm to evaluate
      the epidemiology, quality of care, and outcomes of cardiovascular disease and to
      conduct future clinical trials using a community-based model. The network
      includes 15 geographically distributed health plans with dedicated research
      centers, National Heart, Lung, and Blood Institute representatives, and an
      external collaboration and advisory committee. Cardiovascular research network
      sites bring complementary content and methodological expertise and a diverse
      population of approximately 11 million individuals treated through various health
      care delivery models. Each site's rich electronic databases (eg, sociodemographic
      characteristics, inpatient and outpatient diagnoses and procedures, pharmacy,
      laboratory, and cost data) are being mapped to create a standardized virtual data
      warehouse to facilitate rapid and efficient large-scale research studies. Initial
      projects focus on (1) hypertension recognition and management, (2) quality and
      outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable
      cardioverter defibrillators. CONCLUSIONS: The Cardiovascular Research Network
      represents a new paradigm in the approach to cardiovascular quality of care and
      outcomes research among community-based populations. Its unique ability to
      characterize longitudinally large, diverse populations will yield novel insights
      into contemporary disease and risk factor surveillance, management, outcomes, and
      costs. The Cardiovascular Research Network aims to become the national research
      partner of choice for efforts to improve the prevention, diagnosis, treatment,
      and outcomes of cardiovascular diseases.

PMID- 20031804
TI  - Outcomes research: myths and realities.

PMID- 20031805
TI  - Gender delay in emergency medical services: does it really exist?

PMID- 20031806
TI  - Is anyone too old for an implantable cardioverter-defibrillator?

PMID- 20031807
TI  - Elapsed time in emergency medical services for patients with cardiac complaints:
      are some patients at greater risk for delay?
AB  - BACKGROUND: In patients with a major cardiac event, the first priority is to
      minimize time to treatment. For many patients, first contact with the health
      system is through emergency medical services (EMS). We set out to identify
      patient-level and neighborhood-level factors that were associated with elapsed
      time in EMS. METHODS AND RESULTS: A retrospective cohort study was conducted in
      10 municipalities in Dallas County, Tex, from January 1 through December 31,
      2004. The data set included 5887 patients with suspected cardiac-related
      symptoms. The region was served by 29 hospitals and 98 EMS depots. Multivariate
      models included measures of distance traveled, time of day, day of week, and
      patient and neighborhood characteristics. The main outcomes were elapsed time in
      EMS (continuous; in minutes) and delay in EMS (dichotomous; >15 minutes beyond
      median elapsed time). We found positive associations between patient
      characteristics and both average elapsed time and delay in EMS care. Variation in
      average elapsed time was not large enough to be clinically meaningful. However,
      approximately 11% (n=647) of patients were delayed >or=15 minutes. Women were
      more likely to be delayed (adjusted odds ratio, 1.52; 95% confidence interval,
      1.32 to 1.74), and this association did not change after adjusting for other
      characteristics, including neighborhood socioeconomic composition. CONCLUSIONS:
      Compared with otherwise similar men, women have 50% greater odds of being delayed
      in the EMS setting. The determinants of delay should be a special focus of EMS
      studies in which time to treatment is a priority.

PMID- 20031808
TI  - Impact of age and medical comorbidity on the effectiveness of implantable
      cardioverter-defibrillators for primary prevention.
AB  - BACKGROUND: Although implantable cardioverter-defibrillators (ICDs) reduce
      mortality in primary prevention patients with left ventricular systolic
      dysfunction, recent studies have questioned their overall role in clinical
      practice, especially in older patients and those with major comorbid conditions.
      METHODS AND RESULTS: In a prospective cohort of 965 patients with ischemic and
      nonischemic cardiomyopathies (ejection fraction <or=35%) and no prior ventricular
      arrhythmias, we compared long-term mortality in patients who did (n=494 [51%])
      and did not receive ICDs over a mean follow-up period of 34+/-16 months. Using a
      landmark analysis, multivariable Cox proportional hazards models that included
      propensity scores for ICD implantation assessed the relationship between ICD
      therapy and mortality in the entire cohort and by age and the presence of major
      comorbid conditions. Data from these analyses were then used as inputs in a
      Markov model to generate incremental cost-effectiveness ratios for ICD therapy.
      Patients who received ICDs were similar in age and prevalence of most major
      comorbid conditions, including symptomatic heart failure. After multivariable
      adjustment, ICD therapy was associated with a 31% lower risk for all-cause
      mortality (adjusted hazard ratio, 0.69; 95% CI, 0.50 to 0.96; P=0.03). The
      relationship between ICD therapy and lower all-cause mortality was consistent
      after stratification by age (<65, 65 to 74, and >or=75), ischemic etiology,
      ejection fraction (>25% versus <or=25%), and the presence of major comorbid
      conditions (probability values for all interactions >0.05). Incremental cost
      effectiveness ratios for ICD therapy were similar between patients aged >or=75
      years and younger patients but rose slightly in those with multiple comorbid
      conditions. CONCLUSIONS: Routine use of ICDs in primary prevention patients with
      left ventricular systolic dysfunction was associated with lower all-cause
      mortality, even among older patients and those with major comorbid conditions.
      Although their use needs to be individualized, our findings suggest that these
      groups should not be routinely excluded from ICD treatment.

PMID- 20031809
TI  - Stress reduction prolongs life in women with coronary disease: the Stockholm
      Women's Intervention Trial for Coronary Heart Disease (SWITCHD).
AB  - BACKGROUND: Psychosocial stress may increase risk and worsen prognosis of
      coronary heart disease in women. Interventions that counteract women's
      psychosocial stress have not previously been presented. This study implemented a
      stress reduction program for women and investigated its ability to improve
      survival in women coronary patients. METHODS AND RESULTS: Two hundred thirty
      seven consecutive women patients, aged 75 years or younger, hospitalized for
      acute myocardial infarction, coronary artery bypass grafting, or percutaneous
      coronary intervention were randomized to a group-based psychosocial intervention
      program or usual care. Initiated 4 months after hospitalization, intervention
      groups of 4 to 8 women met for a total of 20 sessions that were spread over a
      year. We provided education about risk factors, relaxation training techniques,
      methods for self-monitoring and cognitive restructuring, with an emphasis on
      coping with stress exposure from family and work, and self-care and compliance
      with clinical advice. From randomization until end of follow-up (mean duration,
      7.1 years), 25 women (20%) in the usual care and 8 women (7%) in the stress
      reduction died, yielding an almost 3-fold protective effect of the intervention
      (odds ratio, 0.33; 95% CI, 0.15 to 0.74; P=0.007). Introducing baseline measures
      of clinical prognostic factors, including use of aspirin, beta-blockers,
      angiotensin-converting enzyme inhibitors, calcium-channel blockers, and statins
      into multivariate models confirmed the unadjusted results (P=0.009). CONCLUSIONS:
      Although mechanisms remain unclear, a group-based psychosocial intervention
      program for women with coronary heart disease may prolong lives independent of
      other prognostic factors.

PMID- 20031810
TI  - Impact of depression on sex differences in outcome after myocardial infarction.
AB  - BACKGROUND: Women have an unexplained worse outcome after myocardial infarction
      (MI) compared with men in many studies. Depressive symptoms predict adverse post
      MI outcomes and are more prevalent among women than men. We examined whether
      depressive symptoms contribute to women's worse outcomes after MI. METHODS AND
      RESULTS: In a prospective multicenter study (PREMIER), 2411 (807 women) MI
      patients were enrolled. Depressive symptoms were assessed with the Patient Health
      Questionnaire. Outcomes included 1-year rehospitalization, presence of angina
      using the Seattle Angina Questionnaire, and 2-year mortality. Multivariable
      analyses were used to evaluate the association between sex and these outcomes,
      adjusting for clinical characteristics. The depressive symptoms score was added
      to the models to evaluate whether it attenuated the association between sex and
      outcomes. Depressive symptoms were more prevalent in women compared with men (29%
      versus 18.8%, P<0.001). After adjusting for demographic factors, comorbidities,
      and MI severity, women had a mildly higher risk of rehospitalization (hazard
      ratio, 1.20; 95% CI, 1.04 to 1.40), angina (odds ratio, 1.32; 95% CI, 1.00 to
      1.75), and mortality (hazard ratio, 1.27; 95% CI, 0.98 to 1.64). After adding
      depressive symptoms to the multivariable models, the relationship further
      declined toward the null, particularly for rehospitalization (hazard ratio, 1.14;
      95% CI, 0.98 to 1.34) and angina (odds ratio, 1.22; 95% CI, 0.91 to 1.63),
      whereas there was little change in the estimate for mortality (hazard ratio,
      1.24; 95% CI, 0.95 to 1.62). Depressive symptoms were significantly associated
      with each of the study outcomes with a similar magnitude of effect in both women
      and men. CONCLUSIONS: A higher prevalence of depressive symptoms in women
      modestly contributes to their higher rates of rehospitalization and angina
      compared with men but not mortality after MI. Our results support the recent
      recommendations of improving recognition of depressive symptoms after MI.

PMID- 20031811
TI  - From here to JUPITER: identifying new patients for statin therapy using data from
      the 1999-2004 National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Guidelines for statin use currently focus on patients with elevated
      low-density lipoprotein levels. Recent findings from the Justification for the
      Use of Statins in Primary Prevention: An Intervention Trial Evaluating
      Rosuvastatin (JUPITER), however, indicate that statin therapy to reduce
      cardiovascular risk is also effective among older persons with at-goal low
      density lipoprotein but elevated high-sensitivity C-reactive protein levels. We
      estimate the size of and describe this new population for whom statin therapy may
      now be indicated based on JUPITER's findings. METHODS AND RESULTS: Using data
      from the 1999 to 2004 National Health and Nutrition Examination Survey, we
      estimate that 57.9% of older adults (men >or=50 years and women >or=60 years), or
      33,547 000 (95% CI, 32,217,000 to 34,877,000) Americans, are currently taking a
      statin (24.4%) or indicated for statin therapy (33.5%). In addition, we estimate
      that 19.2%, or 11 144 000 (95% CI, 10 053 000 to 12 235 000), may become newly
      eligible for statin therapy. This includes 8 071 000 (13.9%; 95% CI, 7 173 000 to
      8 969 000) with high-sensitivity C-reactive protein >or=2 mg/L and low-density
      lipoprotein <130 mg/dL (ie, those meeting "strict" JUPITER criteria) and an
      additional 3,073,000 (5.3%; 95% CI, 2,404,000 to 3,743,000) with high-sensitivity
      C-reactive protein >or=2 mg/L and low-density lipoprotein of 130 to 160 mg/dL for
      whom JUPITER's findings might reasonably be extended. Thus, approximately 80% of
      older persons may now have an indication for statin therapy. Compared with those
      who would continue to have no indication for statin therapy, the JUPITER group
      was more likely to be female, to be older, and to have obesity, hypertension, and
      the metabolic syndrome. CONCLUSIONS: JUPITER's findings have the potential to
      impact treatment recommendations for approximately 20% of middle-aged to elderly
      adults, thus increasing the proportion of this segment of the population with an
      indication for statin therapy to nearly 80%.

PMID- 20031812
TI  - Cost, effectiveness, and cost-effectiveness.

PMID- 20031813
TI  - The limits of cost-effectiveness analysis.

PMID- 20031814
TI  - Questioning conventional wisdom.

PMID- 20031815
TI  - We were fishing for TROUT and we caught a CARP: musings on perioperative
      management in an age of enlightenment.

PMID- 20031816
TI  - Aspirin therapy in women: back to the ABCs.

PMID- 20031818
TI  - Perioperative complications after vascular surgery are predicted by the revised
      cardiac risk index but are not reduced in high-risk subsets with preoperative
      revascularization.
AB  - BACKGROUND: The Revised Cardiac Risk Index (RCRI) is useful for risk stratifying
      patients before noncardiac operations. Among patients with documented coronary
      artery disease who undergo vascular surgery, it is unclear whether preoperative
      revascularization reduces postoperative cardiac complications in high-risk
      subsets defined by the RCRI. METHODS AND RESULTS: The Coronary Artery
      Revascularization Prophylaxis Trial was a randomized, controlled trial that
      tested the long-term benefit of a preoperative coronary artery revascularization
      before elective vascular surgery. Using preoperative baseline characteristics to
      determine the RCRI, we tested the benefit of preoperative revascularization on
      death and nonfatal myocardial infarction in patients with multiple risks. Among
      462 patients undergoing vascular surgery, there were 72 complications (15.6%)
      within 30 days postsurgery, including 15 deaths (3.2%) and 57 nonfatal myocardial
      infarctions (12.3%). The postoperative risk of death and nonfatal myocardial
      infarction after surgery increased according to the RCRI (odds ratio, 1.73; 95%
      CI, 1.26 to 2.38; P<0.001), with a rate of 1.6% in patients with no risk that
      increased to 23.4% in patients with > or =3 risks. Preoperative revascularization
      had no influence on the incidence of complications in any risk subset (odds
      ratio, 0.86; 95% CI, 0.50 to 1.49; P=0.60). Among those individuals with > or =2
      risks who also demonstrated ischemia on a preoperative stress-imaging test
      (N=146), the incidence of events was 23% in patients with and without
      preoperative revascularization (P=0.95). CONCLUSIONS: The risk of death and
      nonfatal myocardial infarction is accurately predicted by the RCRI in patients
      undergoing vascular surgery but is not reduced in any high-risk subset of the
      RCRI with preoperative coronary artery revascularization.

PMID- 20031819
TI  - Aspirin use, dose, and clinical outcomes in postmenopausal women with stable
      cardiovascular disease: the Women's Health Initiative Observational Study.
AB  - BACKGROUND: Despite compelling evidence that aspirin reduces fatal and nonfatal
      vascular events among the overall population in various settings, women have
      frequently been underrepresented and their data underreported. We sought to
      evaluate the relationship between aspirin use, dose (81 or 325 mg), and clinical
      outcomes among postmenopausal women with stable cardiovascular disease (CVD).
      METHODS AND RESULTS: Women with CVD (n=8928) enrolled in the Women's Health
      Initiative Observational Study were used for this analysis. The primary outcome
      was the incidence of all-cause mortality and cardiovascular events (myocardial
      infarction, stroke, and cardiovascular death). Among 8928 women with stable CVD,
      4101 (46%) reported taking aspirin, of whom 30% were on 81 mg and 70% were on 325
      mg. At 6.5 years of follow-up, no significant association was noted for aspirin
      use and all-cause mortality or cardiovascular events. However, after multivariate
      adjustment, aspirin use was associated with a significantly lower all-cause
      (adjusted hazard ratio, 0.86 [0.75 to 0.99]; P=0.04) and cardiovascular-related
      mortality (adjusted hazard ratio, 0.75 [0.60 to 0.95]; P=0.01) compared with no
      aspirin. Aspirin use was associated with a lower risk of cardiovascular events
      (adjusted hazard ratio, 0.90 [0.78 to 1.04]; P=0.14), which did not meet
      statistical significance. Compared with 325 mg, use of 81 mg was not
      significantly different for all-cause mortality, cardiovascular events, or any
      individual end point. CONCLUSIONS: After multivariate adjustment, aspirin use was
      associated with significantly lower risk of all-cause mortality, specifically,
      cardiovascular mortality, among postmenopausal women with stable CVD. No
      significant difference was noted between 81 mg and 325 mg of aspirin. Overall,
      aspirin use was low in this cohort of women with stable CVD.

PMID- 20031821
TI  - Paclitaxel versus sirolimus stents in diabetic and nondiabetic patients.
AB  - BACKGROUND: Drug-eluting stents are more effective in reducing restenosis than
      bare-metal stents. Less certain is the relative performance of 2 widely used drug
      eluting stents-sirolimus- and paclitaxel-eluting stents-in diabetic and
      nondiabetic patients undergoing percutaneous coronary intervention in routine
      clinical practice. We therefore studied the long-term effectiveness and safety of
      sirolimus versus paclitaxel stents overall and stratified by the absence or
      presence of diabetes. METHODS AND RESULTS: We compared sirolimus and paclitaxel
      stents in a propensity-score matched cohort of 2054 pairs of patients (835
      matched pairs of diabetic patients and 1219 matched pairs of nondiabetic
      patients) undergoing percutaneous coronary intervention in Ontario between
      December 1, 2003 and March 31, 2006. The cohort was derived from the Cardiac Care
      Network of Ontario percutaneous coronary intervention registry and linked to
      population-based administrative health databases. In the overall cohort, there
      was no difference in rates of target-vessel revascularization (P=0.47),
      myocardial infarction (P=0.71), or death (P=0.49). As compared with paclitaxel
      stents, the use of sirolimus stents was associated with a significantly lower 3
      year rate of target-vessel revascularization in nondiabetic patients (8.3% versus
      10.0%, P=0.01), but not in diabetic patients (12.7% versus 10.3%, P=0.07). Rates
      of all-cause mortality were similar in patients receiving sirolimus stents versus
      paclitaxel stents in both the diabetic (8.4% versus 9.2%, P=0.91) and nondiabetic
      (4.6% versus 3.0%, P=0.22) groups. CONCLUSIONS: In this large observational
      study, patients receiving paclitaxel and sirolimus stents had similar mortality
      rates, but nondiabetic patients receiving sirolimus stents were significantly
      less likely to require repeat revascularization.

PMID- 20031820
TI  - A 30-year perspective (1975-2005) into the changing landscape of patients
      hospitalized with initial acute myocardial infarction: Worcester Heart Attack
      Study.
AB  - BACKGROUND: The effects of lifestyle changes and evolving treatment practices on
      coronary disease incidence rates, demographic and clinical profile, and the short
      term outcomes of patients hospitalized with acute myocardial infarction have not
      been well characterized. The purpose of this study was to examine multidecade
      long trends (1975-2005) in the incidence rates, demographic and clinical
      characteristics, treatment practices, and hospital outcomes of patients
      hospitalized with an initial acute myocardial infarction from a population-based
      perspective. METHODS AND RESULTS: Residents of the Worcester, Mass, metropolitan
      area (median age, 37 years; 89% white) hospitalized with an initial acute
      myocardial infarction (n=8898) at all greater-Worcester medical centers during 15
      annual periods between 1975 and 2005 comprised the sample of interest. The
      incidence rates of initial acute myocardial infarction were lower in 2005 (209 of
      100,000 population) than in 1975 (277 of 100,000), although these trends varied
      inconsistently over time. Patients hospitalized during the most recent study
      years were significantly older (mean age, 64 years in 1975; 71 years in 2005),
      more likely to be women (38% in 1975; 48% in 2005), and have a greater prevalence
      of comorbidities. Hospitalized patients were increasingly more likely to receive
      effective cardiac medications and coronary interventional procedures for the
      period under investigation. Hospital survival rates improved significantly over
      time (81% survived in 1975; 91% survived in 2005), although varying trends were
      observed in the occurrence of clinically important complications. CONCLUSIONS:
      The results of this community-wide investigation provide insight into the
      changing magnitude, characteristics, management practices, and outcomes of
      patients hospitalized with a first myocardial infarction.

PMID- 20031822
TI  - Use of oseltamivir after influenza infection is associated with reduced incidence
      of recurrent adverse cardiovascular outcomes among military health system
      beneficiaries with prior cardiovascular diseases.
AB  - BACKGROUND: Influenza infection has been associated with increased risk of
      adverse cardiac and cerebral vascular outcomes. Oseltamivir, a treatment for
      influenza, has been shown to decrease the severity of an influenza episode, but
      few data exist regarding its potentially protective effect against recurrent
      vascular outcomes among influenza patients with a history of vascular disease.
      METHODS AND RESULTS: Electronic healthcare service and pharmacy records for
      37,482 TRICARE beneficiaries, aged 18 and older, with a coded history of
      cardiovascular (CV) disease and a subsequent diagnosis of influenza from October
      1, 2003, through September 30, 2007, were examined. Subjects were grouped
      according to whether they had filled a prescription for oseltamivir within 2 days
      of their influenza diagnosis. The incidence of recurrent CV events within 30 days
      after the influenza diagnosis among oseltavmivir-treated and untreated subjects
      was 8.5% and 21.2%, respectively (P<0.005). Subject age was a persistent and
      significant contributor to the likelihood of recurrent CV outcomes. After
      controlling for the differences in demographics among treated and untreated
      cohorts using a propensity-scored logistic regression model, a statistically
      significant protective effect was associated with oseltamivir treatment (odds
      ratio, 0.417; 95% CI, 0.349 to 0.498). CONCLUSIONS: Our findings suggests that
      oseltamivir treatment for influenza is associated with significant decrease in
      the risk of recurrent CV events in subjects with a history of CV disease. These
      findings merit confirmation in further prospective and controlled studies.
      Meanwhile, in patients with CV disease, strict adherence with current practice
      guidelines for prevention and treatment of influenza is recommended.

PMID- 20031823
TI  - Systems-based improvement in door-to-balloon times at a large urban teaching
      hospital: a follow-up study from Parkland Health and Hospital System.
AB  - BACKGROUND: Timely reperfusion in ST-segment elevation myocardial infarction
      (STEMI) patients improves clinical outcomes. Implementing strategies to target
      institutional-specific delays are crucial for improved patient care. METHODS AND
      RESULTS: Using a novel strategy to analyze specific components of door-to-balloon
      time (DBT) at our institution, we previously identified several specific interval
      delays in our prior STEMI protocol. We then implemented 4 strategies to reduce
      DBT: (1) emergency department physician activation of the STEMI protocol; (2)
      "single call" broadcast paging of the STEMI team by the page operator; (3)
      immediate feedback to the emergency and cardiology departments with joint monthly
      quality improvement meetings; and (4) transfer of the off-hours STEMI patient
      directly to the laboratory on activation by an in-hospital team. After
      implementation of the new protocol, we examined each component time interval from
      the first 59 consecutive STEMI patients treated with the new protocol between
      March 2007 and June 2008 and compared time intervals with the previous 184 STEMI
      patients. Compared with the previous 184 STEMI patients, the median DBT of the
      subsequent 59 STEMI patients significantly improved from 125 to 86 minutes
      (P<0.0001). This improvement was largely driven by a decrease in the interval
      from the initial 12-lead ECG to activation of the on-call catheterization team
      (from 40 to 11 minutes, P<0.0001). CONCLUSIONS: After examining specific
      component delays in our institution's DBT, we were able to successfully use
      quality improvement strategies to focus on specific sources of delay in our
      institution. This dramatically improved our median DBT toward the goal of
      achieving a guideline-recommended <90 minutes for all patients.

PMID- 20031824
TI  - Does percutaneous coronary intervention reduce mortality in patients with stable
      chronic angina: are we talking about apples and oranges?

PMID- 20031825
TI  - The cost of end-of-life care: a new efficiency measure falls short of AHA/ACC
      standards.

PMID- 20031826
TI  - Evidence-based financial incentives for healthcare reform: putting it together.

PMID- 20031828
TI  - Medicine in the era of outcomes measurement.

PMID- 20031829
TI  - The challenge of reducing prehospital delay in patients with acute coronary
      syndrome.

PMID- 20031830
TI  - Searching for a safe analgesic in patients with cardiovascular disease.

PMID- 20031817
TI  - Statin cost-effectiveness in the United States for people at different vascular
      risk levels.
AB  - BACKGROUND: Statins reduce the rates of heart attacks, strokes, and
      revascularization procedures (ie, major vascular events) in a wide range of
      circumstances. Randomized controlled trial data from 20,536 adults have been used
      to estimate the cost-effectiveness of prescribing statin therapy in the United
      States for people at different levels of vascular disease risk and to explore
      whether wider use of generic statins beyond the populations currently recommended
      for treatment in clinical guidelines is indicated. METHODS AND RESULTS:
      Randomized controlled trial data, an internally validated vascular disease model,
      and US costs of statin therapy and other medical care were used to project
      lifetime risks of vascular events and evaluate the cost-effectiveness of 40 mg
      simvastatin daily. For an average of 5 years, allocation to simvastatin reduced
      the estimated US costs of hospitalizations for vascular events by approximately
      20% (95% CI, 15 to 24) in the different subcategories of participants studied. At
      a daily cost of $1 for 40 mg generic simvastatin, the estimated costs of
      preventing a vascular death within the 5-year study period ranged from a net
      saving of $1300 (95% CI, $15,600 saving to $13,200 cost) among participants with
      a 42% 5-year major vascular event risk to a net cost of $216,500 ($123,700 to
      $460,000 cost) among those with a 12% 5-year risk. The costs per life year gained
      with lifetime simvastatin treatment ranged from $2500 (-$40 to $3820) in people
      aged 40 to 49 years with a 42% 5-year major vascular event risk to $10,990 ($9430
      to $14,700) in people aged 70 years and older with a 12% 5-year risk.
      CONCLUSIONS: Treatment with generic simvastatin appears to be cost-effective for
      a much wider population in the United States than that recommended by current
      guidelines.

PMID- 20031831
TI  - Understanding why patients delay seeking care for acute coronary syndromes.
AB  - BACKGROUND: Better insight into the psychosocial factors associated with
      prehospital delays in seeking care for acute coronary syndromes is needed to
      inform the design of future interventions. Delay in presenting for care after the
      onset of symptoms is common, limits the potential benefit of acute reperfusion,
      and has not been reduced by interventions tested thus far. METHODS AND RESULTS:
      Seven hundred ninety-six patients with suspected ischemic heart disease scheduled
      for clinically indicated imaging stress tests completed questionnaires concerning
      psychological distress and attachment styles (worthiness to receive care,
      trustworthiness of others to provide care). The primary dependent variable for
      this study was response to a question from the rapid early action for coronary
      treatment trial concerning intention to "wait until very sure" before seeking
      care for a possible "heart attack." Responses to this question were strongly
      associated with actual emergency department-reported and self-reported care delay
      in the rapid early action for coronary treatment trial. In multivariable ordinal
      regression models, a more negative view of the trustworthiness of others, greater
      physical limitations from angina, and no previous revascularization were
      independently associated with increased intention to wait to seek care for a
      myocardial infarction. Intention to wait was not associated with inducible
      ischemia or self-perceived risk of myocardial infarction. CONCLUSIONS: Intention
      to delay seeking care for acute coronary syndromes is associated with a patient's
      view of the trustworthiness of others, previous experience with
      revascularization, and functional limitations, even after adjustment for
      objective and perceived acute coronary syndromes risk. These findings provide
      insight into novel factors contributing to longer delay times and may inform
      future interventions to reduce delay time.

PMID- 20031833
TI  - New-onset postoperative atrial fibrillation after isolated coronary artery bypass
      graft surgery and long-term survival.
AB  - BACKGROUND: The advancing age and generally increasing risk profile of patients
      receiving isolated coronary artery bypass graft (CABG) surgery is expected to
      raise incidence of new-onset postoperative atrial fibrillation (AFIB) resulting
      in potentially higher risk of adverse outcomes. In the early postoperative
      course, new-onset post-CABG AFIB is considered relatively easy to treat and is
      believed to have little impact on patients' long-term outcome. However, little
      has been done to determine the effect of new-onset post-CABG AFIB on long-term
      survival, and this relationship is unclear. METHODS AND RESULTS: Survival was
      assessed in a cohort of 6899 consecutive patients without preoperative AFIB who
      underwent isolated CABG at Baylor University Medical Center, Dallas, Tex, between
      January 1, 1997 and December 31, 2006; patients who died during CABG were
      excluded. Ten-year unadjusted survival was 52.3% (48.4%, 56.0%) for patients with
      new-onset postoperative AFIB and 69.4% (67.3%, 71.4%) for patients without it. A
      propensity-adjusted model controlling for risk factors identified by the Society
      of Thoracic Surgeons and other clinical/nonclinical details was used to
      investigate the association between new-onset AFIB post-CABG and long-term
      survival. After adjustment, new-onset AFIB post-CABG was significantly associated
      (hazard ratio, 1.29; 95% CI, 1.16, 1.45) with increased risk of death.
      CONCLUSIONS: This study provides evidence that new-onset post-CABG AFIB is
      significantly associated with increased long-term risk of mortality independent
      of patient preoperative severity. After controlling for a comprehensive array of
      risk factors associated with post-CABG adverse outcomes, risk of long-term
      mortality in patients that developed new-onset post-CABG AFIB was 29% higher than
      in patients without it.

PMID- 20031832
TI  - Cardiovascular risks of nonsteroidal antiinflammatory drugs in patients after
      hospitalization for serious coronary heart disease.
AB  - BACKGROUND: The cardiovascular safety of individual nonsteroidal antiinflammatory
      drugs (NSAIDs) is highly controversial, particularly in persons with serious
      coronary heart disease. METHODS AND RESULTS: We conducted a multisite
      retrospective cohort study of commonly used individual NSAIDs in Tennessee
      Medicaid, Saskatchewan Health, and United Kingdom General Practice Research
      databases. The cohort included 48566 patients recently hospitalized for
      myocardial infarction, revascularization, or unstable angina pectoris with more
      than 111000 person-years of follow-up. Naproxen users had the lowest adjusted
      rates of serious coronary heart disease (myocardial infarction, coronary heart
      disease death) and serious cardiovascular disease (myocardial infarction,
      stroke)/death from any cause, with respective incidence rate ratios (relative to
      NSAID nonusers) of 0.88 (95% CI, 0.66 to 1.17) and 0.91 (0.78 to 1.06). Risk did
      not increase with doses >or=1000 mg. Relative to NSAID nonusers, serious coronary
      heart disease risk increased with short term (<90 days) use for ibuprofen (1.67
      [1.09 to 2.57]), diclofenac (1.86 [1.18 to 2.92]), celecoxib (1.37 [0.96 to
      1.94]), and rofecoxib (1.46 [1.03 to 2.07]), but not for naproxen (0.88 [0.50 to
      1.55]). Relative to naproxen, current users of diclofenac had increased risk of
      serious coronary heart disease (1.44 [0.96 to 2.15], P=0.076) and serious
      cardiovascular disease/death (1.52 [1.22 to 1.89], P=0.0002), and those of
      ibuprofen had increased risk of the latter end point (1.25 [1.02 to 1.53],
      P=0.032). Compared to naproxen in doses >or=1000 mg, serious coronary heart
      disease incidence rate ratios were increased for rofecoxib >25 mg (2.29 [1.24 to
      4.22], P=0.008) and celecoxib >200 mg (1.61 [1.01 to 2.57], P=0.046).
      CONCLUSIONS: In patients recently hospitalized for serious coronary heart
      disease, naproxen had better cardiovascular safety than did diclofenac,
      ibuprofen, and higher doses of celecoxib and rofecoxib.

PMID- 20031835
TI  - Hazard function and secular trends in the risk of recurrent acute myocardial
      infarction: 30 years of follow-up of more than 775,000 incidents.
AB  - BACKGROUND: The incidence of a first acute myocardial infarction (AMI) has fallen
      considerably during the last decades. However, no previous studies have analyzed
      the underlying hazards function of experiencing a recurrent AMI, and none has
      analyzed the change of risk for a recurrent AMI over the last 3 decades. METHODS
      AND RESULTS: The study was based on the Swedish national myocardial infarction
      register. The register contained more than 1 million AMI events. After exclusion
      of events occurring in subjects younger than 20 or older than 84 years and events
      with uncertain first AMI status, 775 901 events occurring between 1972 and 2001
      remained for analysis. During the study period, the risk of a new event among
      survivors of a previous AMI decreased sharply during the first 2 years after the
      previous event, had its minimum after 5 years, and then increased slowly again.
      The risk for a recurrent AMI during the first year after a previous event was
      fairly stable over the years until the late 1970s and then decreased by 36% in
      women and 40% in men until the late 1990s, irrespective of age and AMI number,
      mirroring the incidence decrease over the years for primary events. CONCLUSIONS:
      The risk of a recurrent AMI event was highly dependent on time from the previous
      event, a novel finding which may affect risk scoring. There were strong secular
      trends toward diminishing risk for a recurrent AMI in recent years, even when
      other outcome affecting variables were taken into account.

PMID- 20031834
TI  - The impact of a multidisciplinary information technology-supported program on
      blood pressure control in primary care.
AB  - BACKGROUND: Hypertension is a leading mortality risk factor yet inadequately
      controlled in most affected subjects. Effective programs to address this problem
      are lacking. We hypothesized that an information technology-supported management
      program could help improve blood pressure (BP) control. METHODS AND RESULTS: This
      randomized controlled trial included 223 primary care hypertensive subjects with
      mean 24-hour BP >130/80 and daytime BP >135/85 mm Hg measured with ambulatory
      monitoring (ABPM). Intervention subjects received a BP monitor and access to an
      information technology-supported adherence and BP monitoring system providing
      nurses, pharmacists, and physicians with monthly reports. Control subjects
      received usual care. The mean (+/-SD) follow-up was 348 (+/-78) and 349 (+/-84)
      days in the intervention and control group, respectively. The primary end point
      of the change in the mean 24-hour ambulatory BP was consistently greater in
      intervention subjects for both systolic (-11.9 versus -7.1 mm Hg; P<0.001) and
      diastolic BP (-6.6 versus -4.5 mm Hg; P=0.007). The proportion of subjects that
      achieved Canadian Guideline target BP (46.0% versus 28.6%) was also greater in
      the intervention group (P=0.006). We observed similar BP declines for ABPM and
      self-recorded home BP suggesting the latter could be an alternative for
      confirming BP control. The intervention was associated with more physician-driven
      antihypertensive dose adjustments or changes in agents (P=0.03), more
      antihypertensive classes at study end (P=0.007), and a trend toward improved
      adherence measured by prescription refills (P=0.07). CONCLUSIONS: This
      multidisciplinary information technology-supported program that provided feedback
      to patients and healthcare providers significantly improved blood pressure levels
      in a primary care setting.

PMID- 20031836
TI  - Effect of race on the clinical outcomes in the bypass angioplasty
      revascularization investigation trial.
AB  - BACKGROUND: In observational studies, clinical outcomes for black patients with
      coronary disease have been worse than for white patients. There are few data from
      randomized trials comparing the outcomes of coronary revascularization between
      black patients and white patients. METHODS AND RESULTS: We analyzed data from the
      Bypass Angioplasty Revascularization Investigation randomized trial. At study
      entry, the 113 black patients had significantly higher rates of diabetes,
      hypertension, smoking, heart failure, and abnormal left ventricular function than
      the 1653 white patients. Black patients had significantly higher mortality than
      white patients (hazard ratio, 2.16; P<0.001), which remained significant after
      statistical adjustment for differences in baseline clinical characteristics
      (hazard ratio, 1.59; P=0.003). In a substudy of economic and quality of life
      outcomes, the 67 black patients had similar frequency of physician visits and use
      of evidence-based cardiac medications but significantly worse physical function
      scores than the 885 white patients. The effect of random assignment to either
      surgery or angioplasty on clinical outcomes was not significantly modified by
      race (interaction probability values >or=0.18). CONCLUSIONS: Clinical outcomes of
      black patients after coronary revascularization were worse than those of white
      patients in a clinical trial setting with similar treatment and access to care.
      The differences in outcome between black and white patients were not completely
      attributable to the greater levels of comorbidity among black patients at study
      entry.

PMID- 20031837
TI  - Detection and elimination of microemboli related to cardiopulmonary bypass.
AB  - BACKGROUND: Neurobehavioral impairment is a common complication of coronary
      bypass surgery. Cerebral microemboli during cardiopulmonary bypass (CPB) are a
      principal mechanism of cognitive injury. The aim of this work was to study the
      occurrence of cerebral embolism during CPB and to evaluate the effectiveness of
      evidence-based CPB circuit component and process changes on the exposure of the
      patient to emboli. METHODS AND RESULTS: M-Mode Doppler was used to detect emboli
      in the inflow and outflow of cardiopulmonary circuit and in the right and left
      middle cerebral arteries. Doppler signals were merged into a single display to
      allow real-time associations between discrete clinical techniques and emboli
      detection. One hundred sixty-nine isolated coronary artery bypass grafting (CABG)
      patients were studied between 2002 and 2008. There was no statistical difference
      in median microemboli detected in the inflow of the CPB circuit, (Phase I, 931;
      Phase II, 1214; Phase III, 1253; Phase IV, 1125; F [3,158]=0.8, P=0.96).
      Significant changes occurred in median microemboli detected in the outflow of the
      CPB circuit across phases, (Phase I, 702; Phase II, 572; Phase III, 596; Phase
      IV, 85; F [3,157]=13.1, P<0.001). Significant changes also occurred in median
      microemboli detected in the brain across phases, (Phase I, 604; Phase II, 429;
      Phase III, 407; Phase IV, 138; F [3,153]=14.4, P<0.001). Changes in the
      cardiopulmonary bypass circuit were associated with an 87.9% (702 versus 85)
      reduction in median microemboli in the outflow of the CPB circuit (P<0.001), and
      a 77.2% (604 versus 146) reduction in microemboli in the brain (P<0.001).
      CONCLUSIONS: Changes in CPB techniques and circuit components, including filter
      size and type of pump, resulted in a reduction in more than 75% of cerebral
      microemboli.

PMID- 20031838
TI  - Use of guidelines-recommended management and outcomes among women and men with
      low-level troponin elevation: insights from CRUSADE.
AB  - BACKGROUND: Troponin elevation above the upper limit of normal (ULN) is
      diagnostic of myocardial infarction, but interpretation of "gray-zone" troponin
      elevations (1 to 1.5x ULN) remains uncertain. Using the CRUSADE database, we
      explored relationships between sex and treatment and outcomes among patients with
      troponin 1 to 1.5x ULN. METHODS AND RESULTS: We compared treatment and outcomes
      among women and men using logistic generalized estimating equation method.
      Overall, 5049 of 85 671 (5.9%) non-ST-segment elevation acute coronary syndromes
      patients (2156 women, 2893 men) had troponin 1 to 1.5x ULN within 24 hours of
      presentation. Compared with troponin >1.5x ULN, "gray-zone" patients less often
      received all guidelines-indicated acute (mean composite score, 63% versus 72%)
      and discharge therapies (mean composite score, 73% versus 78%), but received them
      more frequently than patients with troponin <1x ULN (mean composite scores, 58%
      acute and 67% discharge). Among "gray-zone" patients, acute and discharge therapy
      use was similar between women and men, except acute aspirin (adjusted odds ratio,
      0.80 [95% CI, 0.65 to 0.98]) and discharge angiotensin-converting enzyme
      inhibitors (adjusted odds ratio, 0.77 [95% CI, 0.67 to 0.88]). "Gray-zone"
      patients had lower mortality (2.3%) than the >1.5x ULN (4.5%) group but higher
      than the <1x ULN group (1.1%). Outcomes were similar among "gray-zone" women and
      men (adjusted odds ratios: death, 0.88 [95% CI, 0.58 to 1.35]; death/myocardial
      infarction, 0.77 [95% CI, 0.55 to 1.06]; transfusion, 1.04 [95% CI, 0.85 to
      1.27]). CONCLUSIONS: Patients with non-ST-segment elevation acute coronary
      syndromes and low-level troponin elevations had lower overall risk and received
      less aggressive guidelines-based treatment than those with greater troponin
      elevations, but treatment patterns were largely similar by sex across troponin
      elevation groups.

PMID- 20031839
TI  - Knowledge of heart disease risk among SHIELD respondents with dyslipidemia.
AB  - BACKGROUND: Respondents in the US Study to Help Improve Early evaluation and
      management of risk factors Leading to Diabetes (SHIELD) reported whether they had
      a diagnosis of dyslipidemia, were taking prescription dyslipidemia medication,
      and knew their heart disease risk (low, moderate, high, or do not know). We
      assessed whether respondents who reported a diagnosis of dyslipidemia with or
      without lipid-modifying treatment knew their heart disease risk and whether it
      correlated with National Cholesterol Education Program Adult Treatment Panel
      (ATP) III risk. METHODS AND RESULTS: Based on self-report of risk factors, ATP
      III high risk was defined as diagnosis of heart disease/heart attack,
      narrow/blocked arteries, stroke, or diabetes; moderate risk included >or=2 risk
      factors (ie, men aged >45 years, women aged >55 years, hypertension, low high
      density lipoprotein cholesterol, current smoking, and family history of CHD); and
      low risk included <2 risk factors. Of 7629 respondents with dyslipidemia, 35%
      reported not taking cholesterol medication, and 29% reported not knowing their
      heart disease risk. For respondents treated for dyslipidemia, 27% reported not
      knowing their risk, and of the 73% who reported knowing, 24% to 35% reported the
      same risk level as ATP III risk. For respondents with untreated dyslipidemia, 33%
      reported not knowing their risk, and of the 67% who reported knowing, 20% to 37%
      reported the same risk as ATP III risk. CONCLUSIONS: A large proportion of
      respondents with dyslipidemia did not know their heart disease risk. Among those
      who reported knowing their risk level, >60% of respondents did not classify
      themselves at the same ATP III-defined risk level. There is a gap in
      understanding and awareness of heart disease risk among respondents with
      dyslipidemia regardless of treatment status.

PMID- 20031840
TI  - Psychiatric comorbidity and mortality after acute myocardial infarction.
AB  - BACKGROUND: Prior studies of the impact of psychiatric comorbidity on outcomes
      after acute myocardial infarction (AMI) have frequently relied on inpatient
      secondary diagnosis codes. This study compared associations between psychiatric
      comorbidity and AMI outcomes that were derived using secondary diagnosis codes
      and codes captured from prior outpatient encounters. METHODS AND RESULTS:
      Retrospective cohort study analyzing 21 745 patients admitted in 2004 to 2006 to
      Veterans Health Administration hospitals with AMI using administrative data.
      Psychiatric comorbidity was identified using (1) secondary inpatient diagnosis
      codes from the index hospitalization and (2) diagnoses from prior outpatient
      encounters. Outcomes included 30- and 365-day mortality and the receipt of
      coronary revascularization within 30 days of admission. Generalized estimating
      equations and Cox proportional hazards were used to adjust mortality and receipt
      of revascularization for demographic and clinical variables. Psychiatric
      disorders were identified in 2285 (10%) patients from inpatient secondary
      diagnosis codes and 5225 (24%) patients from prior outpatient codes. Patients
      with psychiatric comorbidity had higher adjusted 30- and 365-day mortality, based
      on outpatient codes (odds ratios, 1.19 [95% CI, 1.09 to 1.30] and 1.12 [95% CI,
      1.03 to 1.22], respectively), but similar mortality based on inpatient codes
      (odds ratios, 0.89 [95% CI, 0.69 to 1.01] and 0.93 [95% CI, 0.82 to 1.06],
      respectively). In contrast, patients with psychiatric comorbidity had lower
      receipt of coronary revascularization based on outpatient codes (hazard ratio,
      0.92; [95% CI, 0.85 to 0.99], but similar receipt based on inpatient codes
      (hazard ratio, 1.00 [95% CI, 0.91 to 1.10]). CONCLUSIONS: Inpatient secondary
      diagnosis codes identified fewer patients with psychiatric comorbidity than prior
      outpatient codes. Moreover, associations with AMI outcomes differed for the 2
      approaches. These findings raise potential concerns about the validity and
      reliability of psychiatric inpatient secondary diagnosis in estimating the impact
      of psychiatric comorbidities on AMI outcomes and in developing risk-adjustment
      models.

PMID- 20031841
TI  - Characteristics and outcomes of America's lowest-performing hospitals: an
      analysis of acute myocardial infarction hospital care in the United States.
AB  - BACKGROUND: Studies suggest that most hospitals now have relatively high
      adherence with recommended acute myocardial infarction (AMI) process measures.
      Little is known about hospitals with consistently poor adherence with AMI process
      measures and whether these hospitals also have increased patient mortality.
      METHODS AND RESULTS: We conducted a retrospective study of 2761 US hospitals
      reporting AMI process measures to the Center for Medicare and Medicaid Services
      Hospital Compare database during 2004 to 2006 that could be linked to 2005
      Medicare Part A data. The main outcome measures were hospitals' combined
      compliance with 5 AMI measures (aspirin and beta-blocker on admission and
      discharge and angiotensin-converting enzyme inhibitor/angiotensin receptor
      blocker use at discharge for patients with left ventricular dysfunction) and risk
      adjusted 30-day mortality for 2005. We stratified hospitals into those with low
      AMI adherence (ranked in the lowest decile for AMI adherence for 3 consecutive
      years [2004-2006, n=105]), high adherence (ranked in the top decile for 3
      consecutive years [n=63]), and intermediate adherence (all others [n=2593]). Mean
      AMI performance varied significantly across low-, intermediate-, and high
      performing hospitals (mean score, 68% versus 92% versus 99%, P<0.001). Low
      performing hospitals were more likely than intermediate- and high-performing
      hospitals to be safety-net providers (19.2% versus 11.0% versus 6.4%; P=0.005).
      Low-performing hospitals had higher unadjusted 30-day mortality rates (23.6%
      versus 17.8% versus 14.9%; P<0.001). These differences persisted after adjustment
      for patient characteristics (16.3% versus 16.0% versus 15.7%; P=0.02).
      CONCLUSIONS: Consistently low-performing hospitals differ substantially from
      other US hospitals. Targeting quality improvement efforts toward these hospitals
      may offer an attractive opportunity for improving AMI outcomes.

PMID- 20031842
TI  - Changes in adherence to evidence-based medications in the first year after
      initial hospitalization for heart failure: observational cohort study from 1994
      to 2003.
AB  - BACKGROUND: The use of evidence-based medications in patients with heart failure
      has increased over the past 10 years. We aimed to determine whether adherence to
      these medications has also increased during this time. METHODS AND RESULTS: A
      retrospective cohort was created using administrative databases from the province
      of Saskatchewan, Canada. Subjects discharged alive from their first
      hospitalization for heart failure between 1994 and 2003 were eligible. Those
      filling a prescription for a beta-blocker (BB), angiotensin-converting enzyme
      inhibitor (ACEI), or angiotensin receptor blocker (ARB) within 6 months of
      discharge were followed for 1 year after the initial prescription. Of 8805
      eligible patients, 67% of BB users (941/1414) and 74% of ACEI/ARB users
      (4441/5991) exhibited optimal adherence at 1 year (defined as >or=80% adherence
      calculated from pharmacy refill records). When grouped by year of initial heart
      failure hospitalization, the proportion of optimally adherent patients improved
      from 54% to 75% with BB and from 67% to 80% with ACEI/ARBs between 1994/1995 and
      2002/2003 (P for trend <0.001 for both). Mean 1-year adherence improved from 71%
      to 83% for BB and 80% to 88% for ACEI/ARBs. After adjustment using multivariable
      logistic regression, subjects discharged in 2003 were significantly more likely
      to exhibit optimal adherence to a BB (odds ratio, 2.04; 95% CI, 1.21 to 3.44) or
      an ACEI/ARB (odds ratio, 1.65; 95% CI, 1.30 to 2.08) than those prescribed
      therapy in 1994/1995. CONCLUSIONS: One-year adherence to BB and ACEI/ARB is
      improving over time in patients discharged after first heart failure
      hospitalization. Patients taking multiple cardiac medications were not any less
      likely to exhibit optimal adherence than patients taking only 1 medication.

PMID- 20031843
TI  - National heart, lung, and blood institute-initiated program "interventions to
      improve hypertension control rates in African Americans": background and
      implementation.

PMID- 20031844
TI  - Home-based blood pressure interventions for blacks.
AB  - Efforts to increase blood pressure (BP) control rates in blacks, a traditionally
      underserved high-risk population must address both provider practice and patient
      adherence issues. The home-based BP Intervention for blacks study is a 3-arm
      randomized controlled trial designed to test 2 strategies to improve hypertension
      management and outcomes in a decentralized service setting serving a vulnerable
      and complex home care population. The primary study outcomes are systolic BP,
      diastolic BP, and BP control; secondary outcomes are nurse adherence to
      hypertension management recommendations and patient adherence to medication,
      healthy diet, and other self-management strategies. Nurses (n=312) in a nonprofit
      Medicare-certified home health agency are randomized along with their eligible
      hypertensive patients (n=845). The 2 interventions being tested are (1) a "basic"
      intervention delivering key evidence-based reminders to home care nurses and
      patients while the patient is receiving traditional postacute home health care;
      and (2) an "augmented" intervention that includes that same as the basic
      intervention, plus transition to an ongoing Hypertension Home Support Program
      that extends support for 12 months. Outcomes are measured at 3 and 12 months
      after baseline interview. The interventions will be assessed relative to usual
      care and to each other. Systems change to improve BP management and outcomes in
      home health will not easily occur without new intervention models and rigorous
      evaluation of their impact. Results from this trial will provide important
      information on potential strategies to improve BP control in a low-income
      chronically ill patient population.

PMID- 20031845
TI  - Counseling African Americans to Control Hypertension (CAATCH) trial: a multi
      level intervention to improve blood pressure control in hypertensive blacks.
AB  - Despite strong evidence of effective interventions targeted at blood pressure
      (BP) control, there is little evidence on the translation of these approaches to
      routine clinical practice in care of hypertensive blacks. The goal of this study
      is to evaluate the effectiveness of a multilevel, multicomponent, evidence-based
      intervention compared with usual care in improving BP control among hypertensive
      blacks who receive care in community health centers. The primary outcomes are BP
      control rate at 12 months and maintenance of intervention 1 year after the trial.
      The secondary outcomes are within-patient change in BP from baseline to 12 months
      and cost-effectiveness of the intervention. Counseling African Americans to
      Control Hypertension (CAATCH) is a group randomized clinical trial with 2
      conditions: intervention condition and usual care. Thirty community health
      centers were randomly assigned equally to the intervention condition group (n=15)
      or the usual care group (n=15). The intervention comprises 3 components targeted
      at patients (interactive computerized hypertension education, home BP monitoring,
      and monthly behavioral counseling on lifestyle modification) and 2 components
      targeted at physicians (monthly case rounds based on Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
      guidelines, chart audit and provision of feedback on clinical performance and
      patients' home BP readings). All outcomes are assessed at quarterly study visits
      for 1 year. Chart review is conducted at 24 months to evaluate maintenance of
      intervention effects and sustainability of the intervention. Poor BP control is
      one of the major reasons for the mortality gap between blacks and whites.
      Findings from this study, if successful, will provide salient information needed
      for translation and dissemination of evidence-based interventions targeted at BP
      control into clinical practice for this high-risk population.

PMID- 20031846
TI  - Does reducing physician uncertainty improve hypertension control?: rationale and
      methods.
AB  - Hypertension affects nearly one third of the US population overall, and the
      prevalence rises sharply with age. In spite of public educational campaigns and
      professional education programs to encourage blood pressure measurement and
      control of both systolic and diastolic control to <140/90 mm Hg (or 130/80 mm Hg
      if diabetic), 43% of treated hypertensives do not achieve the recommended Seventh
      Report of the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure target. Among blacks, 48% are uncontrolled on
      treatment. The majority of persons classified as poorly controlled hypertensives
      have mild systolic blood pressure elevation (in the range of 140 to 160 mm Hg).
      We hypothesized that physician uncertainty regarding the patient's usual blood
      pressure, as well as uncertainty regarding the extent of medication nonadherence,
      represent an important barrier to further reductions in the proportion of
      uncontrolled hypertensives in the United States. Using cluster randomization, 10
      primary care clinics (6 from a public health care system and 4 from a private
      clinic system) were randomized to either the uncertainty reduction intervention
      condition or to usual care. An average of 68 patients per clinic were recruited
      to serve as units of observation. Physicians in the 5 intervention clinics were
      provided with a specially designed study form that included a graph of recent
      blood pressure measurements in their study patients, a check box to indicate
      their assessment of the adequacy of the patient's blood pressure control, and a
      menu of services they could order to aid in patient management. These menu
      options included 24-hour ambulatory blood pressure monitoring; electronic bottle
      cap assessment of medication adherence, followed by medication adherence
      counseling in patients found to be nonadherent; and lifestyle assessment and
      counseling followed by 24-hour ambulatory blood pressure monitoring. Physicians
      in the 5 usual practice clinics did not have access to these services but were
      informed of which patients had been enrolled in the study. Substudies carried out
      to further characterize the study population and interpret intervention results
      included ambulatory blood pressure monitoring and electronic bottle cap
      monitoring in a random subsample of patients at baseline, and audio recording of
      patient-physician encounters after intervention implementation. The primary study
      end point was defined as the proportion of patients with controlled blood
      pressure (<140/90 mm Hg or <130/80 mm Hg if diabetic). Secondary end points
      include actual measured clinic systolic and diastolic blood pressure, patient
      physician communication patterns, physician prescribing patient self-reported
      lifestyle and medication adherence, physician knowledge, attitude and beliefs
      regarding the utility of intervention tools to achieve blood pressure control,
      and the cost-effectiveness of the intervention. Six-hundred eighty patients have
      been randomized, and 675 remain in active follow-up after 1.5 years. Patient
      closeout will be complete in March 2009. Analyses of the baseline data are in
      progress. Office-based blood pressure measurement error and bias, as well as
      physician and patient beliefs about the need for treatment intensification, may
      be important factors that limit further progress in blood pressure control. This
      trial will provide data on the extent to which available technologies not widely
      used in primary care will change physician prescribing behavior and patient
      adherence to prescribed treatment.

PMID- 20031847
TI  - The Team Education and Adherence Monitoring (TEAM) trial: pharmacy interventions
      to improve hypertension control in blacks.
AB  - Recent studies suggest that involving pharmacists is an effective strategy for
      improving patient adherence and blood pressure (BP) control. To date, few
      controlled studies have tested the cost-effectiveness of specific models for
      improving patient adherence and BP control in community pharmacies, where most
      Americans obtain prescriptions. We hypothesized that a team model of adherence
      monitoring and intervention in corporately owned community pharmacies can improve
      patient adherence, prescribing, and BP control among hypertensive black patients.
      The Team Education and Adherence Monitoring (TEAM) Trial is a randomized
      controlled trial testing a multistep intervention for improving adherence
      monitoring and intervention in 28 corporately owned community pharmacies.
      Patients in the 14 control pharmacies received "usual care," and patients in the
      14 intervention pharmacies received TEAM Care by trained pharmacists and pharmacy
      technicians working with patients and physicians. Data collectors screened 1250
      patients and enrolled 597 hypertensive black patients. The primary end points
      were the proportion of patients achieving BP control and reductions in systolic
      and diastolic BP measured after 6 and 12 months. Secondary end points were
      changes in adherence monitoring and intervention, patient adherence and barriers
      to adherence, prescribing, and cost-effectiveness. Researchers also will examine
      potential covariates and barriers to change. Involving pharmacists is a
      potentially powerful means of improving BP control in blacks. Pharmacists are in
      an excellent position to monitor patients between clinic visits and to provide
      useful information to patients and physicians.

PMID- 20031848
TI  - Hypertension telemanagement in blacks.
AB  - We propose evaluation of a multi-component home automated telemanagement system
      providing integrated support to both clinicians and patients in implementing
      hypertension treatment guidelines. In a randomized clinical study, 550 blacks
      with hypertension are followed for 18 months. The major components of the
      intervention and control groups are identical and are based on the current
      standard of care. For the purpose of this study, we define "standard of care" as
      the expected evidence-based care provided according to the current hypertension
      treatment guidelines. Although intervention and control groups are similar in
      terms of their care components, they differ in the mode of care delivery. For the
      control group the best attempt is made to deliver all components of a guideline
      concordant care in a routine clinical environment whereas for the intervention
      group the routine clinical environment is enhanced with health information
      technology that assists clinicians and patients in working together in
      implementing treatment guidelines. The home automated telemanagement system
      guides patients in following their individualized treatment plans and helps care
      coordination team in monitoring the patient progress. The study design is aimed
      at addressing the main question of this trial: whether the addition of the
      information technology-enhanced care coordination in the routine primary care
      setting can improve delivery of evidence-based hypertension care in blacks. The
      outcome parameters include quality of life, medical care use, treatment
      compliance, psychosocial variables, and improvement in blood pressure control
      rates. The trial will provide insight on the potential impact of information
      technology-enhanced care coordination in blacks with poorly controlled
      hypertension.

PMID- 20031849
TI  - The JUPITER trial: results, controversies, and implications for prevention.

PMID- 20031850
TI  - JUPITER: a few words of caution.

PMID- 20031851
TI  - Medicine should be more like Missouri.

PMID- 20031852
TI  - Angiographic profiles in courage.

PMID- 20031853
TI  - Improving quality: lessons from the Department of Veterans Affairs.

PMID- 20031854
TI  - Should patient characteristics influence target anticoagulation intensity for
      stroke prevention in nonvalvular atrial fibrillation?: the ATRIA study.
AB  - BACKGROUND: Randomized trials and observational studies support using an
      international normalized ratio (INR) target of 2.0 to 3.0 for preventing ischemic
      stroke in atrial fibrillation. We assessed whether the INR target should be
      adjusted based on selected patient characteristics. METHODS AND RESULTS: We
      conducted a case-control study nested within the ATRIA cohort's 9217 atrial
      fibrillation patients taking warfarin to define the relationship between INR
      level and the odds of thromboembolism (TE; mainly stroke) and of intracranial
      hemorrhage (ICH) relative to INR 2.0 to 2.5. We identified 396 TE cases and 164
      ICH cases during follow-up. Each case was compared with 4 randomly selected
      controls matched on calendar date and stroke risk factors using matched
      univariable analyses and conditional logistic regression. We explored
      modification of the INR-outcome relationships by the following stroke risk
      factors: prior stroke, age, and CHADS(2) risk score. Overall, the odds of TE were
      low and stable above INR 1.8. Compared with INR 2.0 to 2.5, the relative odds of
      TE increased strikingly at INR <1.8 (eg, odds ratio, 3.72; 95% CI, 2.67 to 5.19,
      at INR 1.4 to 1.7). The odds of ICH increased markedly at INR values >3.5 (eg,
      odds ratio, 3.56; 95% CI: 1.70 to 7.46, at INR 3.6 to 4.5). The relative odds of
      ICH were consistently low at INR <3.6. There was no evidence of lower ICH risk at
      INR levels <2.0. These patterns of risk did not differ substantially by history
      of stroke, age, or CHADS(2) risk score. CONCLUSIONS: Our results confirm that the
      current standard of INR 2.0 to 3.0 for atrial fibrillation falls in the optimal
      INR range. Our findings do not support adjustment of INR targets according to
      previously defined stroke risk factors.

PMID- 20031855
TI  - Increasing healthcare resource utilization after coronary artery bypass graft
      surgery in the United States.
AB  - BACKGROUND: Despite declining lengths of stay, postdischarge healthcare resource
      utilization may be increasing because of shifts to nonacute care settings.
      Although changes in hospital stay after coronary artery bypass graft (CABG)
      surgery have been described, patterns of discharge remain unclear. Our objective
      was to determine patterns of discharge disposition after CABG surgery in the
      United States. METHODS AND RESULTS: We examined discharge disposition after CABG
      procedures from 1988 to 2005 using the Nationwide Inpatient Sample. Discharges
      with a "nonroutine" disposition defined patients discharged with continued
      healthcare needs. Multivariable regression models were constructed to assess
      trends and factors associated with nonroutine discharge. Median length of stay
      among 8,398,554 discharges decreased from 11 to 8 days between 1988 and 2005
      (P<0.0001). There was a simultaneous increase in nonroutine discharges from 12%
      in 1988 to 45% in 2005 (P<0.0001), primarily comprising home healthcare and long
      term facility use. Multivariable regression models showed age, female gender,
      comorbidities, concurrent valve surgery, and lower-volume hospitals more likely
      to be associated with nonroutine discharge. CONCLUSIONS: We found a significant
      increase in nonroutine discharges after CABG surgery across the United States
      from 1988 to 2005. The significant shortening of length of stay during CABG may
      be counterbalanced by the increased requirement for additional postoperative
      healthcare services. Nonacute care institutions are playing an increasingly
      significant role in providing CABG patients with postdischarge healthcare and
      should be considered in investigations of postoperative healthcare resource
      utilization. The impact of these changes on long-term outcomes and net resource
      utilization remain unknown.

PMID- 20031856
TI  - Extent of the decrease of 28-day case fatality of hospitalized patients with
      acute myocardial infarction over 22 years: epidemiological versus clinical view:
      the MONICA/KORA Augsburg infarction registry.
AB  - BACKGROUND: No data exist regarding time trends of 28-day case fatality (CF) of
      patients with presumed acute myocardial infarction (AMI) using epidemiological
      criteria, clinical criteria, and AMI classification after validation of presumed
      in-hospital AMI-related deaths (gold-standard criteria). METHODS AND RESULTS:
      From 1985 to 2004, we prospectively examined all 9210 AMI patients consecutively
      hospitalized in a large teaching hospital by using a broad epidemiological AMI
      definition (WHO-MONICA). Twenty-eight-day CF decreased significantly from 32% in
      1985-1986 to 18% in 2003-2004, mostly because of a reduction in early deaths (<24
      hours). When applying the clinical AMI definition, most of the early deaths were
      not counted as AMI related. A retrospective validation process from a sample of
      all early deceased patients by the epidemiological AMI definition (388/2076) and
      a prospective validation of the complete cohort in 2005-2006 revealed that only
      about 50% of early deaths are reclassified as a real fatal AMI using newer
      criteria resulting in a 28-day CF of 23% in 1985-1986 and 11% in 2005-2006. The
      difference between the AMI 28-day CF by applying gold-standard criteria and the
      clinical AMI 28-day CF (18% in 1985-1986 and 7% in 2005-2006) has decreased
      during recent years. CONCLUSIONS: The application of broad epidemiological
      criteria for AMI overestimates 28-day CF by almost 2-fold compared with gold
      standard criteria (after validation of early deaths) and almost 3-fold compared
      to the clinical definition. The growing similarity in 28-day CF between the
      clinically based definition and the gold-standard criteria implies that recent
      clinical-based registries may represent a realistic picture of trends regarding
      in-hospital AMI mortality.

PMID- 20031857
TI  - Quantitative results of baseline angiography and percutaneous coronary
      intervention in the COURAGE trial.
AB  - BACKGROUND: COURAGE compared outcomes in stable coronary patients randomized to
      optimal medical therapy plus percutaneous coronary intervention (PCI) versus
      optimal medical therapy alone. METHODS AND RESULTS: Angiographic data were
      analyzed by treatment arm, health care system (Veterans Administration, US non
      Veterans Administration, Canada), and gender. Veterans Administration patients
      had higher prevalence of coronary artery bypass graft surgery and left
      ventricular ejection fraction < or =50%. Men had worse diameter stenosis of the
      most severe lesion, higher prevalence of prior coronary artery bypass graft
      surgery, lower left ventricular ejection fraction, and more 3-vessel disease that
      included a proximal left anterior descending lesion (P<0.0001 for all comparisons
      versus women). Failure to cross rate (3%) and visual angiographic success of
      stent procedures (97%) were similar to contemporary practice in the National
      Cardiovascular Data Registry. Quantitative angiographic PCI success was 93%
      (residual lesion <50% in-segment) and 82% (<20% in-stent), with only minor
      nonsignificant differences among health care systems and genders. Event rates
      were higher in patients with higher jeopardy scores and more severe vessel
      disease, but rates were similar irrespective of treatment strategy. Within the
      PCI plus optimal medical therapy arm, complete revascularization was associated
      with a trend toward lower rate of death or nonfatal myocardial infarction.
      Complete revascularization was similar between genders and among health care
      systems. CONCLUSIONS: PCI success and completeness of revascularization did not
      differ significantly by health care system or gender and were similar to
      contemporary practice. Angiographic burden of disease affected overall event
      rates but not response to an initial strategy of PCI plus optimal medical therapy
      or optimal medical therapy alone.

PMID- 20031858
TI  - The association of cognitive and somatic depressive symptoms with depression
      recognition and outcomes after myocardial infarction.
AB  - BACKGROUND: Among patients with acute myocardial infarction (AMI), depression is
      both common and underrecognized. The association of different manifestations of
      depression, somatic and cognitive, with depression recognition and long-term
      prognosis is poorly understood. METHODS AND RESULTS: Depression was confirmed in
      481 AMI patients enrolled from 21 sites during their index hospitalization with a
      Patient Health Questionnaire (PHQ-9) score > or =10. Within the PHQ-9, separate
      somatic and cognitive symptom scores were derived, and the independent
      association between these domains and the clinical recognition of depression, as
      documented in the medical records, was evaluated. In a separate multisite AMI
      registry of 2347 patients, the association between somatic and cognitive
      depressive symptoms and 4-year all-cause mortality and 1-year all-cause
      rehospitalization was evaluated. Depression was clinically recognized in 29%
      (n=140) of patients. Cognitive depressive symptoms (relative risk per SD
      increase, 1.14; 95% CI, 1.03 to 1.26; P=0.01) were independently associated with
      depression recognition, whereas the association for somatic symptoms and
      recognition (relative risk, 1.04; 95% CI, 0.87 to 1.26; P=0.66) was not
      significant. However, unadjusted Cox regression analyses found that only somatic
      depressive symptoms were associated with 4-year mortality (hazard ratio [HR] per
      SD increase, 1.22; 95% CI, 1.08 to 1.39) or 1-year rehospitalization (HR, 1.22;
      95% CI, 1.11 to 1.33), whereas cognitive manifestations were not (HR for
      mortality, 1.01; 95% CI, 0.89 to 1.14; HR for rehospitalization, 1.01; 95% CI,
      0.93 to 1.11). After multivariable adjustment, the association between somatic
      symptoms and rehospitalization persisted (HR, 1.16; 95% CI, 1.06 to 1.27; P=0.01)
      but was attenuated for mortality (HR, 1.07; 95% CI, 0.94 to 1.21; P=0.30).
      CONCLUSIONS: Depression after AMI was recognized in fewer than 1 in 3 patients.
      Although cognitive symptoms were associated with recognition of depression,
      somatic symptoms were associated with long-term outcomes. Comprehensive screening
      and treatment of both somatic and cognitive symptoms may be necessary to optimize
      depression recognition and treatment in AMI patients.

PMID- 20031859
TI  - Medication underuse during long-term follow-up in patients with peripheral
      arterial disease.
AB  - BACKGROUND: Patients with peripheral arterial disease constitute a high-risk
      population. Guideline-recommended medical therapy use is therefore of utmost
      importance. The aims of our study were to establish the patterns of guideline
      recommended medication use in patients with PAD at the time of vascular surgery
      and after 3 years of follow up, and to evaluate the effect of these therapies on
      long-term mortality in this patient group. METHODS AND RESULTS: Data on 711
      consecutive patients with peripheral arterial disease undergoing vascular surgery
      were collected from 11 hospitals in the Netherlands (enrollment between May and
      December 2004). After 3.1+/-0.1 years of follow-up, information on medication use
      was obtained by a questionnaire (n=465; 84% response rate among survivors).
      Guideline-recommended medical therapy use for the combination of aspirin and
      statins in all patients and beta-blockers in patients with ischemic heart disease
      was 41% in the perioperative period. The use of perioperative evidence-based
      medication was associated with a reduction of 3-year mortality after adjustment
      for clinical characteristics (hazard ratio, 0.65; 95% CI, 0.45 to 0.94). After 3
      years of follow-up, aspirin was used in 74%, statins in 69%, and beta-blockers in
      54% of the patients respectively. Guideline-recommended medical therapy use for
      the combination of aspirin, statins, and beta-blockers was 50%. CONCLUSIONS: The
      use of guideline recommended therapies in the perioperative period was associated
      with reduction in long-term mortality in patients with peripheral arterial
      disease. However, the proportion of patients receiving these evidence-based
      treatments-both at baseline and 3 years after vascular surgery-was lower than
      expected based on the current guidelines. These data highlight a clear
      opportunity to improve the quality of care in this high-risk group of patients.

PMID- 20031860
TI  - Economic impact of angina after an acute coronary syndrome: insights from the
      MERLIN-TIMI 36 trial.
AB  - BACKGROUND: Angina in patients with coronary artery disease is associated with
      worse quality of life; however, the relationship between angina frequency and
      resource utilization is unknown. METHODS AND RESULTS: Using data from the MERLIN
      TIMI 36 trial, we assessed the association between the extent of angina after an
      acute coronary syndrome (ACS) and subsequent cardiovascular resource utilization
      among 5460 stable outpatients who completed the Seattle Angina Questionnaire at 4
      months after an ACS and who were then followed for an additional 8 months. Angina
      frequency was categorized as none (score, 100; 2739 patients), monthly (score, 61
      to 99; 1608 patients), weekly (score, 31 to 60; 854 patients), and daily (score,
      0 to 30; 259 patients). Multivariable regression models evaluated the association
      between angina frequency and overall costs attributable to cardiovascular
      hospitalizations, outpatient visits and procedures, and medications. As compared
      with no angina, overall costs increased in a graded fashion with higher angina
      frequency-no angina, $2928 (reference); monthly angina, $3909 (adjusted relative
      cost ratio, 1.29; 95% CI, 1.21 to 1.39); weekly angina, $4558 (adjusted relative
      cost ratio, 1.52; 95% CI, 1.48 to 1.67); and daily angina, $6949 (adjusted
      relative cost ratio, 2.32; 95% CI, 2.01 to 2.69; P for trend <0.001). Differences
      in costs were attributable primarily to higher rates of ACS hospitalization and
      coronary revascularization among patients with more severe angina. CONCLUSIONS:
      Among stable outpatients after ACS, a direct graded relationship was found
      between higher angina frequency and healthcare costs. As compared with patients
      without angina, patients with daily angina had a >2-fold increase in resource
      utilization and incremental costs of $4000 after 8 months of follow-up.

PMID- 20031861
TI  - Association of socioeconomic position and medical insurance with fetal diagnosis
      of critical congenital heart disease.
AB  - BACKGROUND: Access to beneficial novel healthcare technology has been inequitable
      in the United States. Fetal echocardiography, used with increasing frequency for
      prenatal diagnosis (PD) of congenital heart disease, allows for optimal neonatal
      management and possible improved outcomes. We sought to evaluate whether PD of
      critical congenital heart disease is related to socioeconomic (SE) position,
      medical insurance, and race. METHODS AND RESULTS: In a retrospective review of
      infants with critical congenital heart disease who underwent surgical or catheter
      intervention at age <30 days in our institution during 2003 to 2006, we extracted
      6 SE variables for the block groups of patient residence from 2000 US Census and
      calculated a previously validated composite SE score for each patient. PD
      occurred in 222 (50%) infants. Race was not significantly associated with PD.
      Private insurance patients were much more likely to have PD (odds ratio, 3.7
      versus public insurance; 95% CI, 2.4 to 5.7; P<0.001), as were patients of higher
      SE position (PD, 62% in highest quartile versus 35% in lowest quartile; P=0.001).
      Odds of PD increased with increasing SE score (odds ratio, 1.7, 2.3, and 2.9 for
      each quartile of higher SE score versus those in lowest SE quartile; P<0.001).
      Patients from economically poor neighborhoods were less likely to have PD (odds
      ratio, 1.2 for each 10% increase in prevalence of poverty; P=0.04). Private
      medical insurance (odds ratio, 3.4; 95% CI, 2.1 to 5.5; P<0.001) was the
      strongest predictor of PD in the logistic regression model. CONCLUSIONS: Patients
      with public insurance and lower SE position are less likely to have a PD of
      critical congenital heart disease.

PMID- 20031862
TI  - A qualitative study to identify barriers to local implementation of prehospital
      termination of resuscitation protocols.
AB  - BACKGROUND: Despite the existence of national American Heart Association
      guidelines and 2 termination-of-resuscitation (TOR) rules for ceasing efforts in
      refractory out-of-hospital cardiac arrest, many emergency medical services
      agencies in the United States have adopted their own local protocols. Public
      policies and local perceptions may serve as barriers or facilitators to
      implementing national TOR guidelines at the local level. METHODS AND RESULTS:
      Three focus groups, lasting 90 to 120 minutes, were conducted at the National
      Association of Emergency Medical Services Physicians meeting in January 2008.
      Snowball sampling was used to recruit participants. Two reviewers analyzed the
      data in an iterative process to identify recurrent and unifying themes. We
      identified 3 distinct groups whose current policies or perceptions may impede
      efforts to adopt national TOR guidelines: payers who incentivize transport;
      legislators who create state mandates for transport and allow only narrow use of
      do-not-resuscitate orders; and communities where cultural norms are perceived to
      impede termination of resuscitation. Our participants suggested that national
      organizations, such as the American Heart Association and American College of
      Emergency Physicians, may serve as potential facilitators in addressing these
      barriers by taking the lead in asking payers to change reimbursement structures;
      encouraging legislators to revise laws to reflect the best available medical
      evidence; and educating the public that rapid transport to the hospital cannot
      substitute for optimal provision of prehospital care. CONCLUSIONS: We have
      identified 3 influential groups who will need to work with national organizations
      to overcome current policies or prevailing perceptions that may impede
      implementing national TOR guidelines.

PMID- 20031863
TI  - Serum selenium concentrations and hypertension in the US Population.
AB  - BACKGROUND: Selenium is an antioxidant micronutrient with potential interest for
      cardiovascular disease prevention. Few studies have evaluated the association
      between selenium and hypertension, with inconsistent findings. We explored the
      relationship of serum selenium concentrations with blood pressure and
      hypertension in a representative sample of the US population. METHODS AND
      RESULTS: We undertook a cross-sectional analysis of 2638 adults > or =40 years
      old who participated in the 2003 to 2004 National Health and Nutrition
      Examination Survey. Serum selenium was measured by inductively coupled plasma
      dynamic reaction cell-mass spectrometry. Hypertension was defined as blood
      pressure > or =140/90 mm Hg or current use of antihypertensive medication. Mean
      serum selenium was 137.1 microg/L. The multivariable adjusted differences (95%
      CIs) in blood pressure levels comparing the highest (> or =150 microg/L) to the
      lowest (<122 microg/L) quintile of serum selenium were 4.3 (1.3 to 7.4), 1.6 (
      0.5 to 3.7), and 2.8 (0.8 to 4.7) mm Hg for systolic, diastolic, and pulse
      pressure, respectively. The corresponding odds ratio for hypertension was 1.73
      (1.18 to 2.53). In spline regression models, blood pressure levels and the
      prevalence of hypertension increased with increasing selenium concentrations up
      to 160 microg/L. CONCLUSIONS: High serum selenium concentrations were associated
      with higher prevalence of hypertension. These findings call for a thorough
      evaluation of the risks and benefits associated with high selenium status in the
      United States.

PMID- 20031864
TI  - Representativeness of a national heart failure quality-of-care registry:
      comparison of OPTIMIZE-HF and non-OPTIMIZE-HF Medicare patients.
AB  - BACKGROUND: Participation in clinical registries is nonrandom, so participants
      may differ in important ways from nonparticipants. The extent to which findings
      from clinical registries can be generalized to broader populations is unclear.
      METHODS AND RESULTS: We linked data from the Organized Program to Initiate
      Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF)
      registry with 100% inpatient Medicare fee-for-service claims to identify matched
      and unmatched patients with heart failure. We evaluated differences in baseline
      characteristics and mortality, all-cause readmission, and cardiovascular
      readmission rates. We used Cox proportional hazards models to examine
      relationships between registry enrollment and outcomes, controlling for baseline
      characteristics. There were 25,245 OPTIMIZE-HF patients in the Medicare claims
      data and 929,161 Medicare beneficiaries with heart failure who were not enrolled
      in OPTIMIZE-HF. Although hospital characteristics differed, patient demographic
      characteristics and comorbid conditions were similar. In-hospital mortality for
      OPTIMIZE-HF and non-OPTIMIZE-HF patients was not significantly different (4.7%
      versus 4.5%; P=0.37); however, OPTIMIZE-HF patients had slightly higher 30-day
      (11.9% versus 11.2%; P<0.001) and 1-year unadjusted mortality (37.2% versus
      35.7%; P<0.001). Controlling for other variables, OPTIMIZE-HF patients were
      similar to non-OPTIMIZE-HF patients for the hazard of mortality (hazard ratio,
      1.02; 95% confidence interval, 0.98 to 1.06). There were small but significant
      decreases in all-cause (hazard ratio, 0.94; 95% CI, 0.92 to 0.97) and
      cardiovascular readmission (hazard ratio, 0.94; 95% CI, 0.91 to 0.98).
      CONCLUSIONS: Characteristics and outcomes of Medicare beneficiaries enrolled in
      OPTIMIZE-HF are similar to the broader Medicare population with heart failure,
      suggesting that findings from this clinical registry may be generalized.

PMID- 20031865
TI  - Comparing methods of measuring treatment intensification in hypertension care.
AB  - BACKGROUND: Greater treatment intensification (TI) improves hypertension control.
      However, we do not know the ideal way to measure TI for research and quality
      improvement efforts. We compared the ability of different TI measures to predict
      blood pressure (BP) control. METHODS AND RESULTS: We enrolled 819 hypertensive
      outpatients from an urban academic hospital. Each patient was assigned 3 scores
      to characterize TI. The any/none score divides patients into those who had any
      therapy increases during the study versus none. The norm-based method models the
      chance of a medication increase at each visit, then scores each patient based on
      whether they received more or fewer medication increases than predicted. The
      standard-based method is similar to the norm-based method but expects a
      medication increase whenever the blood pressure is uncontrolled. We compared the
      ability of these scores to predict the final systolic blood pressure (SBP). The
      any/none score showed a paradoxical result: any therapy increase was associated
      with SBP 4.6 mm Hg higher than no increase (P<0.001). The norm-based method score
      did not predict SBP in a linear fashion (P=0.18); further investigation revealed
      a U-shaped relationship between the norm-based method score and SBP. However, the
      standard-based method score was a strong linear predictor of SBP (2.1 mm Hg lower
      for each additional therapy increase per 10 visits, P<0.001). Similarly, the
      standard-based method predicted dichotomized blood pressure control, as measured
      by SBP <140 mm Hg (odds ratio, 1.30; P<0.001). CONCLUSIONS: Our results suggest
      that standard-based method is the preferred measure of treatment intensity for
      hypertension care.

PMID- 20031866
TI  - Quality improvement initiatives improve hypertension care among veterans.
AB  - BACKGROUND: We implemented a quality improvement initiative to improve
      hypertension care at Veterans Affairs-Tennessee Valley Healthcare System. METHODS
      AND RESULTS: We implemented multiple interventions among 2 teaching hospitals, 5
      community-based outpatient clinics, and 4 contract clinic sites. Goals of the
      program were to (1) improve measurement and documentation of blood pressure (BP),
      (2) initiate outpatient patient education, (3) emphasize VA/Department of Defense
      hypertension treatment algorithms to providers, (4) emphasize external peer
      review program performance goals, and (5) initiate feedback of each clinic's
      performance. The primary outcome was the proportion of patients seen each week
      with a diagnosis of hypertension who had their last available BP in control (< or
      =140/90 mm Hg). Observation time was 40 weeks (14 weeks preintervention, 8 weeks
      intervention implementation, and 18 weeks postintervention), during which there
      were 55 586 unique clinic visits for hypertension. After intervention deployment,
      there was an absolute improvement of 4.2% in BP control (preintervention 61.5%
      [12 245/19 908] versus postintervention 65.7% [15 809/24 059], P<0.0001).
      Teaching hospital A had an absolute improvement of 1.4% (63.4% [3544/5591] versus
      64.8% [4581/7073], P=0.108). Teaching hospital B showed a 0.8% absolute
      improvement in BP control (59.7% [2577/4315] versus 60.5% [3416/5650], P=0.456).
      The community-based outpatient clinics had a combined absolute improvement of
      8.6% (60.2% [5252/8728] versus 68.8% [6895/10025], P<0.0001). The contract
      clinics had a combined improvement of 1.5% (68.4% [872/1274] versus 69.9%
      [917/1311], P=0.409). Results were sustained 1 year after intervention.
      CONCLUSIONS: After implementing small, focused, and inexpensive interventions, BP
      control improved 4.2%, thereby improving the quality of hypertension care.

PMID- 20031867
TI  - One year at circulation: cardiovascular quality and outcomes.

PMID- 20031868
TI  - Controversies and opportunities in economic analysis of health care.

PMID- 20031869
TI  - Cardiovascular disease surveillance in the comparative effectiveness landscape.

PMID- 20031870
TI  - Patterns of hospital performance in acute myocardial infarction and heart failure
      30-day mortality and readmission.
AB  - BACKGROUND: In 2009, the Centers for Medicare & Medicaid Services is publicly
      reporting hospital-level risk-standardized 30-day mortality and readmission rates
      after acute myocardial infarction (AMI) and heart failure (HF). We provide
      patterns of hospital performance, based on these measures. METHODS AND RESULTS:
      We calculated the 30-day mortality and readmission rates for all Medicare fee-for
      service beneficiaries ages 65 years or older with a primary diagnosis of AMI or
      HF, discharged between July 2005 and June 2008. We compared weighted risk
      standardized mortality and readmission rates across Hospital Referral Regions and
      hospital structural characteristics. The median 30-day mortality rate was 16.6%
      for AMI (range, 10.9% to 24.9%; 25th to 75th percentile, 15.8% to 17.4%; 10th to
      90th percentile, 14.7% to 18.4%) and 11.1% for HF (range, 6.6% to 19.8%; 25th to
      75th percentile, 10.3% to 12.0%; 10th to 90th percentile, 9.4% to 13.1%). The
      median 30-day readmission rate was 19.9% for AMI (range, 15.3% to 29.4%; 25th to
      75th percentile, 19.5% to 20.4%; 10th to 90th percentile, 18.8% to 21.1%) and
      24.4% for HF (range, 15.9% to 34.4%; 25th to 75th percentile, 23.4% to 25.6%;
      10th to 90th percentile, 22.3% to 27.0%). We observed geographic differences in
      performance across the country. Although there were some differences in average
      performance by hospital characteristics, there were high and low hospital
      performers among all types of hospitals. CONCLUSIONS: In a recent 3-year period,
      30-day risk-standardized mortality rates for AMI and HF varied among hospitals
      and across the country. The readmission rates were particularly high.

PMID- 20031871
TI  - Temporal changes in the use of drug-eluting stents for patients with non-ST
      Segment-elevation myocardial infarction undergoing percutaneous coronary
      intervention from 2006 to 2008: results from the can rapid risk stratification of
      unstable angina patients supress ADverse outcomes with early implementation of
      the ACC/AHA guidelines (CRUSADE) and acute coronary treatment and intervention
      outcomes network-get with the guidelines (ACTION-GWTG) registries.
AB  - BACKGROUND: The risks of late stent thrombosis with drug-eluting stents (DES)
      were intensely debated after the presentation of a number of studies highlighting
      this issue in September 2006. We evaluated trends in the use of DES for patients
      with non-ST-elevation myocardial infarction undergoing percutaneous coronary
      intervention (PCI) from 2006 to 2008. METHODS AND RESULTS: Temporal patterns of
      DES use were examined among non-ST-elevation myocardial infarction patients in
      the Can Rapid risk stratification of Unstable angina patients Supress ADverse
      outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE; January
      2006 to December 2006) and Acute Coronary Treatment and Intervention Outcomes
      Network-Get With The Guidelines (ACTION-GWTG; January 2007 to June 2008)
      registries to determine how practice patterns changed for patients with acute
      myocardial infarction undergoing PCI. Among the 54 662 patients analyzed, the
      percentage of patients undergoing PCI by quarter varied from 54% to 58% during
      the analysis time period. More than 90% of patients undergoing PCI received a DES
      in the first 3 quarters of 2006 before the public debate about the risks of DES
      began. Thereafter, the use of DES for PCI patients declined during the fourth
      quarter of 2006 through the first quarter of 2007 (82% to 67%), gradually
      declined during quarters 2 to 4 of 2007 (63% to 63% to 59%) but then slightly
      increased from the first to second quarter of 2008 (58% to 60%). Hospital
      characteristics did not seem to correlate with temporal changes in DES use, but
      by the last 2 quarters of the study period, patient characteristics such as white
      race, hypertension, diabetes mellitus, and private or managed care insurance were
      more common among patients who received a DES compared with the beginning 2
      quarters of the study period. CONCLUSIONS: These findings highlight how rapidly
      treatment decisions in contemporary practice can be affected by public debate
      related to scientific presentations and publications.

PMID- 20031872
TI  - Cost-effectiveness of therapeutic hypothermia after cardiac arrest.
AB  - BACKGROUND: Therapeutic hypothermia can improve survival and neurological
      outcomes in cardiac arrest survivors, but its cost-effectiveness is uncertain. We
      sought to evaluate the cost-effectiveness of treating comatose cardiac arrest
      survivors with therapeutic hypothermia. METHODS AND RESULTS: A decision model was
      developed to capture costs and outcomes for patients with witnessed out-of
      hospital ventricular fibrillation arrest who received conventional care or
      therapeutic hypothermia. The Hypothermia After Cardiac Arrest (HACA) trial
      inclusion criteria were assumed. Model inputs were determined from published
      data, cooling device companies, and consultation with resuscitation experts.
      Sensitivity analyses and Monte Carlo simulations were performed to identify
      influential variables and uncertainty in cost-effectiveness estimates. The main
      outcome measures were quality-adjusted survival after cardiac arrest, cost of
      hypothermia implementation, cost of posthospital discharge care, and incremental
      cost-effectiveness ratios. In our model, postarrest patients receiving
      therapeutic hypothermia gained an average of 0.66 quality-adjusted life years
      compared with conventional care, at an incremental cost of $31,254. This yielded
      an incremental cost-effectiveness ratio of $47,168 per quality-adjusted life
      year. Sensitivity analyses demonstrated that poor neurological outcome
      postcooling and costs associated with posthypothermia care (in-hospital and long
      term) were the most influential variables in the model. Even at extreme estimates
      for costs, the cost-effectiveness of hypothermia remained less than $100,000 per
      quality-adjusted life year. In 91% of 10,000 Monte Carlo simulations, the
      incremental cost-effectiveness ratio was less than $100,000 per quality-adjusted
      life year. CONCLUSIONS: In cardiac arrest survivors who meet HACA criteria,
      therapeutic hypothermia with a cooling blanket improves clinical outcomes with
      cost-effectiveness that is comparable to many economically acceptable health care
      interventions in the United States.

PMID- 20031873
TI  - Cost-effectiveness of genotype-guided warfarin dosing for patients with atrial
      fibrillation.
AB  - BACKGROUND: CYP2C9 and VKORC1 genotyping has been advocated as a means of
      improving the accuracy of warfarin dosing. However, the effectiveness of
      genotyping in improving anticoagulation control and reducing major bleeding has
      not yet been compellingly demonstrated. Genotyping currently costs $400 to $550.
      METHODS AND RESULTS: We constructed a Markov model to evaluate whether and under
      what circumstances genetically-guided warfarin dosing could be cost-effective for
      newly diagnosed atrial fibrillation patients. Estimates of clinical event rates,
      treatment and adverse event costs, and utilities for health states were derived
      from the published literature. The cost-effectiveness of genetically-guided
      dosing was highly dependent on the assumed effectiveness of genotyping in
      increasing the amount of time patients spend appropriately anticoagulated. If
      genotyping increases the time spent in the target international normalized ratio
      range by <5 percentage points, its incremental cost-effectiveness ratio would be
      greater than $100,000 per quality-adjusted life year. The incremental cost
      effectiveness ratio falls below $50,000 per quality-adjusted life year if
      genotyping increases the time spent in range by 9 percentage points. The results
      were also sensitive to assumptions about the rate of major bleeding events during
      treatment initiation and the cost of the test. CONCLUSIONS: Our results suggest
      that genotyping before warfarin initiation will be cost-effective for patients
      with atrial fibrillation only if it reduces out-of-range international normalized
      ratio values by more than 5 to 9 percentage points compared with usual care.
      Given the current uncertainty surrounding genotyping efficacy, caution should be
      taken in advocating the widespread adoption of this strategy.

PMID- 20031874
TI  - Iatrogenic adverse events in the coronary care unit.
AB  - BACKGROUND: Although our understanding of medical adverse events has increased
      substantially over the last decade, little is known about iatrogenic adverse
      events (IAEs) in the coronary care unit (CCU). We sought to determine the
      frequency and potential preventability of IAEs in the CCU of a tertiary care
      center. METHODS AND RESULTS: We undertook a retrospective cohort study evaluating
      the hospital charts of consecutive patients admitted to the CCU at Hamilton
      General Hospital (Ontario, Canada) from November 1, 2005, to January 1, 2006. We
      used a priori developed definitions to determine whether patients suffered an IAE
      and whether it was potentially preventable. We included 194 patients, and 99
      (51%; 95% CI, 44% to 58%) patients had at least 1 IAE, of which 45 (45%; 95% CI,
      36% to 55%) were judged potentially preventable. Bleeding (14/51, 27%; 95% CI,
      17% to 41%) was the most common potentially preventable IAE and was more common
      than recurrent ischemic events (4/51, 8%; 95% CI, 3% to 19%). Of the patients who
      died in the hospital, 9 of 17 (53%; 95% CI, 31% to 74%) had an IAE that was
      causally related to their death, of which 6 (67%; 95% CI, 35% to 88%) were judged
      potentially preventable. CONCLUSIONS: The present study suggests that IAEs,
      especially bleeding, are common in the CCU setting and more frequent than
      recurrent ischemic events. These results suggest the need for large multicenter
      studies to evaluate in CCUs the rates of IAEs, their causes, and potential
      preventability.

PMID- 20031875
TI  - Trends in 10-year predicted risk of cardiovascular disease in the United States,
      1976 to 2004.
AB  - BACKGROUND: There have been significant bidirectional changes in the prevalence
      of cardiovascular (CV) risk factors over time in the United States, making the
      net trend in risk for incident CV disease unknown. We assessed these trends by
      applying the Framingham Heart Study prediction model to national data. METHODS
      AND RESULTS: The National Health and Nutrition Examination Survey (NHANES) II
      (1976-1980), NHANES III (1988-1994), and NHANES 1999-2004 are cross-sectional
      representative samples of the noninstitutionalized population of the United
      States. We excluded people with a history of CV disease, pregnant women,
      participants with missing CV risk factors data, and individuals outside the
      Framingham age range of 30 to 74 years. The Framingham risk function was used to
      estimate the 10-year risk for incident symptomatic CV disease. We calculated the
      slope of change or rate of change per year between NHANES II and III, and between
      NHANES III and 1999-2004. The difference between slopes was calculated and
      compared to zero. The average age-adjusted 10-year CV risk between NHANES II and
      III decreased from 10.0% to 7.9% between NHANES II and III, with a statistically
      significant slope (P<0.001). However, the average age-adjusted CV risk decreased
      at a lesser magnitude between NHANES III and NHANES 1999-2004 from 7.9% to 7.4%
      (P<0.001). These slopes were significantly different (P<0.0001). In women and
      middle-aged participants, CV risk did not change between NHANES III and NHANES
      1999-2004 (P=0.40). CONCLUSIONS: The estimated net risk for CV disease in the US
      population decreased from 1976-1980 to 1988-1994 but has changed minimally from
      1988-1994 to 1999-2004, particularly in women and middle-aged people.

PMID- 20031876
TI  - Sociodemographic and clinical characteristics are not clinically useful
      predictors of refill adherence in patients with hypertension.
AB  - BACKGROUND: Although many studies have identified patient characteristics or
      chronic diseases associated with medication adherence, the clinical utility of
      such predictors has rarely been assessed. We attempted to develop clinical
      prediction rules for adherence with antihypertensive medications in 2 healthcare
      delivery systems. METHODS AND RESULTS: We performed retrospective cohort studies
      of hypertension registries in an inner-city healthcare delivery system (n=17 176)
      and a health maintenance organization (n=94 297) in Denver, Colo. Adherence was
      defined by acquisition of 80% or more of antihypertensive medications. A
      multivariable model in the inner-city system found that adherent patients (36.3%
      of the total) were more likely than nonadherent patients to be older, white,
      married, and acculturated in US society, to have diabetes or cerebrovascular
      disease, not to abuse alcohol or controlled substances, and to be prescribed
      fewer than 3 antihypertensive medications. Although statistically significant,
      all multivariate odds ratios were 1.7 or less, and the model did not accurately
      discriminate adherent from nonadherent patients (C statistic=0.606). In the
      health maintenance organization, where 72.1% of patients were adherent,
      significant but weak associations existed between adherence and older age, white
      race, the lack of alcohol abuse, and fewer antihypertensive medications. The
      multivariate model again failed to accurately discriminate adherent from
      nonadherent individuals (C statistic=0.576). CONCLUSIONS: Although certain
      sociodemographic characteristics or clinical diagnoses are statistically
      associated with adherence to refills of antihypertensive medications, a
      combination of these characteristics is not sufficiently accurate to allow
      clinicians to predict whether their patients will be adherent with treatment.

PMID- 20031877
TI  - Improved clinical outcome after acute myocardial infarction in hospitals
      participating in a Swedish quality improvement initiative.
AB  - BACKGROUND: The Swedish quality improvement initiative Quality Improvement in
      Coronary Care previously demonstrated significant improvements in caregiver
      adherence to national guidelines for acute myocardial infarction. The associated
      impact on 1-year clinical outcome is presented here. METHODS AND RESULTS: During
      the baseline period July 2001 to June 2002, 6878 consecutive acute myocardial
      infarction patients <80 years were included at the 19 intervention and 19 control
      hospitals and followed for a mean of 12 months. During the postintervention
      period of May 2003 to April 2004, 6484 patients were included and followed in the
      same way. From baseline to postintervention, improvements in mortality and
      cardiovascular readmission rates (events per 100 patient-years) were significant
      in the intervention group (-2.82, 95% CI -5.26 to -0.39; -9.31, 95% CI -15.48 to 
      3.14, respectively). However, in the control hospitals, there were no significant
      improvements (0.04, 95% CI -2.40 to 2.47; -4.93, 95% CI -11.10 to 1.24,
      respectively). Bleedings in the control group increased in incidence (0.92, 95%
      CI 0.41 to 1.43), whereas the incidence remained unchanged in the intervention
      group (0.07, 95% CI -0.44 to 0.58). When the difference of changes between the
      study groups were evaluated, the results still were in favor of the intervention
      group, albeit significant only for bleeding complications (mortality: -2.70, 95%
      CI -6.37 to 0.97; cardiovascular readmissions: -6.85, 95% CI -16.62 to 2.93;
      bleeding complications: -0.82, 95% CI -1.66 to 0.01). CONCLUSIONS: With a
      systematic quality improvement initiative aiming to increase the adherence to
      acute myocardial infarction guidelines, it is possible to achieve long-term
      positive effects on clinical outcome.

PMID- 20031878
TI  - Job matters: differences in risk assessment of percutaneous aortic valve
      replacement between cardiologists and cardiac surgeons.
AB  - BACKGROUND: Percutaneous aortic valve replacement (PAVR) for aortic stenosis is
      an attractive alternative to operative valve replacement. Several devices are
      evaluated, but their efficacy and safety are critically discussed. An
      interdisciplinary approach with collaboration of cardiac surgeons and
      cardiologists is widely requested. We analyzed how cardiologists and cardiac
      surgeons assess the possibilities and risks of PAVR and whether there are
      substantial differences between the judgments of these 2 groups. METHODS AND
      RESULTS: Fifty-one cardiologists and 54 cardiac surgeons from German hospitals
      completed an online questionnaire consisting of 11 questions dealing with typical
      risks and benefits of PAVR. Answers to all questions differed significantly
      between surgeons and cardiologists. Risks as impaired hemodynamic outcome,
      paravalvular leakage, or embolic events were deemed higher for PAVR than for an
      operation from both groups, but cardiologists rated those risks significantly
      lower than cardiac surgeons (P<0.01 for all questions). A regression analysis
      with a latent variable approach for possible advantages of PAVR (like minor
      operative trauma, faster recovery, less pain) showed that the fact of being a
      cardiologist has a significant impact on the rating of PAVR advantages (r=0.719,
      P<0.01), whereas personal experience showed no significant effect. CONCLUSIONS:
      Cardiologists and cardiac surgeons agree on possible risks and advantages of
      PAVR, but the extent differs significantly between the 2 groups. Cardiologists
      have a far more optimistic view of PAVR and are likely to favor an interventional
      approach. More and better evidence based information may help to overcome group
      related prejudices.

PMID- 20031879
TI  - Survivor treatment selection bias and outcomes research: a case study of surgery
      in infective endocarditis.
AB  - BACKGROUND: Recent studies in infective endocarditis have suggested an
      association between surgery and reduced mortality. However, these studies did not
      account for survivor treatment selection bias, which is an underrecognized source
      of error in observational studies. Therefore, we sought to evaluate the effects
      of survivor bias on surgical outcomes in infective endocarditis. METHODS AND
      RESULTS: We studied 223 patients admitted with left-sided infective endocarditis
      between 1996 and 2006 and compared all-cause mortality between surgically treated
      and medically treated patients using Cox regression analysis. Propensity scores
      were used to account for selection bias, and time-dependent analyses were
      performed to account for survivor bias. Compared with medical patients (n=161),
      surgical patients (n=62) had lower mortality during a median follow-up of 5.2
      years (32% versus 51%; P=0.02) with an unadjusted hazard ratio of 0.54 (95% CI,
      0.33 to 0.88, P=0.01). After adjustment for baseline differences in propensity
      for surgery and risk of mortality, there remained a significant benefit for
      surgery (hazard ratio, 0.50; 95% CI, 0.28 to 0.88; P=0.02). However, this was
      diminished after time-dependent analysis (hazard ratio, 0.77; 95% CI, 0.42 to
      1.40; P=0.39). Conditional Kaplan-Meier analyses confirmed the effect of survivor
      bias because the apparent benefit of surgery was primarily attributable to excess
      mortality in the medical group during early hospitalization when surgery was not
      frequently performed. CONCLUSIONS: Survivor bias significantly affects the
      evaluation of surgical outcomes in infective endocarditis, and it should be
      considered in other areas of outcomes research where randomized controlled trials
      are not feasible. Survivor bias is not corrected by propensity analysis alone but
      may be reduced by time-dependent survival analysis.

PMID- 20031880
TI  - Age- and sex-specific trends in fatal incidence and hospitalized incidence of
      stroke in Scotland, 1986 to 2005.
AB  - BACKGROUND: Temporal trends in stroke incidence are unclear. We aimed to examine
      age- and sex-specific temporal trends in incidence of fatal and nonfatal
      hospitalized stroke in Scotland from 1986 to 2005. METHODS AND RESULTS: Mean age
      at the time of first stroke was 70.8 (SD, 12.9) years in men and 76.4 (12.9)
      years in women. Between 1986 and 2005, rates fell in men from 235 (95% CI, 229 to
      242) to 149 (144 to 154) and in women from 299 (292 to 306) to 182 (177 to 188).
      Poisson modeling showed that temporal trends were influenced by age with declines
      in incidence of hospitalized stroke starting later in younger than older age
      groups. In both men and women aged under 55 years, the overall incidence rate of
      stroke was significantly higher in 2005 than in 1986. CONCLUSIONS: We report in a
      whole country that the overall incidence of stroke declined steadily and
      substantially between 1986 and 2005, with a relative reduction in the risk of
      stroke of 31% in men and 42% in women. Reductions in rates of both hospitalized
      and nonhospitalized fatal stroke contributed to this overall decline. The
      increase in incident stroke rates in young people is of concern.

PMID- 20031881
TI  - Impact of restrictive prescription plans on heart failure medication use.
AB  - BACKGROUND: Prescription plans frequently use restrictive strategies to control
      drug expenditures. Increased restrictions may reduce access to evidence-based
      therapy among patients with chronic disease. We sought to evaluate the impact of
      increased restrictions on medication use among heart failure (HF) patients.
      METHODS AND RESULTS: We conducted a population-based cohort study of
      administrative data from 3 Canadian provinces. During 1998 to 2001, Quebec (QC)
      had a minimally restrictive plan, whereas Ontario (ON) and British Columbia (BC)
      had more restrictive prescription plans. We evaluated drug use at 30 days of
      discharge stratified by prescription plan. Provincial rates of filled
      prescriptions for HF drugs in QC, ON, and BC were 62%, 58%, and 47% for
      angiotensin-converting enzyme inhibitors; 34%, 22%, and 16% for beta-blockers;
      9%, 5%, and 3% for angiotensin receptor blockers; and 79%, 76%, and 62% for loop
      diuretics, respectively. In multivariate analyses, patients residing in provinces
      with restrictive plans were less likely to be prescribed drugs that were
      restricted, such as beta-blockers (odds ratio, 0.53; 95% CI, 0.46 to 0.60; 0.36,
      0.29 to 0.44, for ON and BC, respectively) and angiotensin receptor blockers
      (0.50, 0.45 to 0.56; 0.38, 0.32 to 0.46, for ON and BC, respectively), than drugs
      with no restrictions, such as loop diuretics (0.81, 0.74 to 0.88; 0.40, 0.36 to
      0.45, for ON and BC, respectively) and angiotensin-converting enzyme inhibitors
      (0.80, 0.75 to 0.86; 0.47, 0.43 to 0.52, for ON and BC, respectively).
      CONCLUSIONS: Among HF patients, residing in a province with a more restrictive
      prescription plan may be associated with lower use of restricted HF medications
      over and above the expected regional differences in HF drug use across provinces.

PMID- 20031882
TI  - A call to ACTION (acute coronary treatment and intervention outcomes network): a
      national effort to promote timely clinical feedback and support continuous
      quality improvement for acute myocardial infarction.
AB  - BACKGROUND: There is a recognized need for a national unified registry to track
      presenting features, care, and outcomes for patients with acute myocardial
      infarction. To address this need, the American Heart Association's Get With the
      Guidelines-Coronary Artery Disease program joined the Acute Coronary Treatment
      and Intervention Outcomes Network (ACTION) Registry to create the National
      Cardiovascular Data Registry ACTION-Get With the Guidelines (AR-G) in June of
      2008. This article outlines the objectives, operational structure, patient
      population, data elements, data collection methodology, and reporting components
      of this landmark registry. METHODS AND RESULTS: The AR-G was launched in January
      of 2007. The registry is led by a team of volunteers from the American Heart
      Association and the American College of Cardiology, and its data coordinating
      center resides at the Duke Clinical Research Institute. As of December 2008, 344
      US hospitals already contributed detailed clinical information on 103 890
      myocardial infarction patients (inclusive of 39% ST-segment myocardial infarction
      and 61% non-ST-segment myocardial infarction patients). Overall data quality has
      been excellent, with <5% clinical fields missing. Site quality improvement
      efforts are supported via detailed quarterly feedback reports, routine web
      educational programs, and sharing of "best practice" clinical support tools.
      CONCLUSIONS: The AR-G represents a unified, national, acute myocardial infarction
      registry and supports a robust quality improvement effort designed to encourage
      evidence-based acute myocardial infarction care and, ultimately, improve patient
      outcomes.

PMID- 20031883
TI  - Statistical models and patient predictors of readmission for acute myocardial
      infarction: a systematic review.
AB  - BACKGROUND: Readmission after acute myocardial infarction (AMI) has been targeted
      for public reporting because it is a common, costly, and often preventable
      outcome. To assist in ongoing efforts to risk-stratify patients and profile
      hospitals through public reporting of performance measures, we conducted a
      systematic review to identify models designed to compare hospital rates of
      readmission or predict patients' risk of readmission after AMI and to identify
      studies evaluating patient characteristics associated with AMI readmission.
      METHODS AND RESULTS: We identified relevant English-language studies published
      between 1950 and 2007 by searching MEDLINE, Scopus, PsycINFO, and all 4 Ovid
      Evidence-Based Medicine Reviews. Eligible publications reported on readmission up
      to 1 year after AMI hospitalization among adults. From 751 potentially relevant
      articles, 35 met our predefined inclusion/exclusion criteria. Overall, none
      developed models to compare readmission rates among hospitals or models to
      predict patients' risk of readmission. All 35 examined patient characteristics
      associated with AMI readmission. However, studies varied in methods for case and
      outcome identification, used multiple types of data sources, examined differing
      outcomes (often either readmission alone or a composite outcome of readmission or
      death) over varying follow-up periods (from 30 days to 1 year), and found few
      patient characteristics consistently associated with readmission. CONCLUSIONS:
      Patient characteristics may be important predictors of AMI readmission; however,
      few variables were consistently identified. Thus, clinically, patient risk
      stratification is challenging. From a policy perspective, a validated risk
      standardized model to profile hospitals using AMI readmission rates is currently
      unavailable in the literature.

PMID- 20031884
TI  - Sustaining improvement in door-to-balloon time over 4 years: the Mayo clinic ST
      elevation myocardial infarction protocol.
AB  - BACKGROUND: American College of Cardiology/American Heart Association guidelines
      recommend a door-to-balloon time (DTB) <90 minutes for nontransferred patients
      with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous
      coronary intervention. Systems of care to achieve and sustain this DTB
      performance over several years have not been previously reported. METHODS AND
      RESULTS: The Mayo Clinic STEMI protocol was implemented in April 2004 and
      included activation of the cardiac catheterization laboratory by the emergency
      medicine physician; a single call system to activate the catheterization
      laboratory; catheterization laboratory staff arrival within 20 to 30 minutes of
      activation; and real-time performance feedback within 24 to 48 hours. Data were
      collected on nontransferred STEMI patients. The preimplementation group (June
      2002 to March 2004) comprised 96 patients with a median DTB of 97 (interquartile
      range, 82, 130) minutes, and 40% had a DTB <90 minutes. The postimplementation
      group (May 2004 to March 2008) comprised 322 patients with a median DTB of 67
      (interquartile range, 55, 82) minutes, and 81% had a DTB <90 minutes.
      Postimplementation DTB was significantly shorter than preimplementation DTB
      (P<0.001). In the 4-year follow-up after protocol implementation, the DTB
      performance remained stable over time (P=0.41). CONCLUSIONS: The Mayo Clinic
      STEMI protocol implemented strategies to reduce DTB for nontransferred patients
      with STEMI. DTB was significantly reduced, and the results were sustained over
      the 4-year follow-up period. Our experience demonstrates the effectiveness and
      durability of process changes targeting timeliness of primary percutaneous
      coronary intervention.

PMID- 20031885
TI  - Patients as mercenaries?: the ethics of using financial incentives in the war on
      unhealthy behaviors.

PMID- 20031886
TI  - Registries and selection bias: the need for accountability.

PMID- 20031887
TI  - Sharing decision making about cardiac surgery: improving the quality of the
      decision to undergo or forego surgery.

PMID- 20031888
TI  - Patient education to reduce prehospital delay time in acute coronary syndrome:
      necessary but not sufficient.

PMID- 20031889
TI  - A randomized clinical trial to reduce patient prehospital delay to treatment in
      acute coronary syndrome.
AB  - BACKGROUND: Delay from onset of acute coronary syndrome (ACS) symptoms to
      hospital admission continues to be prolonged. To date, community education
      campaigns on the topic have had disappointing results. Therefore, we conducted a
      clinical randomized trial to test whether an intervention tailored specifically
      for patients with ACS and delivered one-on-one would reduce prehospital delay
      time. METHODS AND RESULTS: Participants (n=3522) with documented coronary heart
      disease were randomized to experimental (n=1777) or control (n=1745) groups.
      Experimental patients received education and counseling about ACS symptoms and
      actions required. Patients had a mean age of 67+/-11 years, and 68% were male.
      Over the 2 years of follow-up, 565 patients (16.0%) were admitted to an emergency
      department with ACS symptoms a total of 842 times. Neither median prehospital
      delay time (experimental, 2.20 versus control, 2.25 hours) nor emergency medical
      system use (experimental, 63.6% versus control, 66.9%) was different between
      groups, although experimental patients were more likely than control to call the
      emergency medical system if the symptoms occurred within the first 6 months
      following the intervention (P=0.036). Experimental patients were significantly
      more likely to take aspirin after symptom onset than control patients
      (experimental, 22.3% versus control, 10.1%, P=0.02). The intervention did not
      result in an increase in emergency department use (experimental, 14.6% versus
      control, 17.5%). CONCLUSIONS: The education and counseling intervention did not
      lead to reduced prehospital delay or increased ambulance use. Reducing the time
      from onset of ACS symptoms to arrival at the hospital continues to be a
      significant public health challenge. CLINICAL TRIAL REGISTRATION:
      clinicaltrials.gov. Identifier NCT00734760.

PMID- 20031890
TI  - Evaluation of patients with severe symptomatic aortic stenosis who do not undergo
      aortic valve replacement: the potential role of subjectively overestimated
      operative risk.
AB  - BACKGROUND: Some patients with severe symptomatic aortic stenosis (AS) do not
      undergo aortic valve replacement (AVR) despite demonstrated symptomatic and
      survival advantages and despite unequivocal guideline recommendations for
      surgical evaluation. METHODS AND RESULTS: In 3 large tertiary care institutions
      (university, Veterans Affairs, and private practice) in Washtenaw County, Mich,
      patients were identified with unrefuted echocardiography/Doppler evidence of
      severe AS during calendar year 2005. Medical records were retrospectively
      reviewed for symptoms, referral for AVR, calculated operative risk for AVR, and
      rationale as to why patients did not undergo valve replacement. Of 369 patients
      with severe AS, 191 (52%) did not undergo AVR. Of these, 126 (66%, 34% of total)
      had symptoms consistent with AS. The most common reasons cited for absent
      intervention were comorbidities with high operative risk (61 patients [48%]),
      patent refusal (24 patients [19%]), and symptoms unrelated to AS (24 patients
      [19%]). Operated patients had a lower Society of Thoracic Surgery-calculated
      perioperative mortality risk than unoperated patients (1.8% [interquartile range,
      1.0 to 3.0%] versus 2.7% [interquartile range, 1.6 to 5.5%], P<0.001). However,
      28 (24%) of 126 unoperated symptomatic patients had a calculated perioperative
      risk less than the median risk for patients who underwent AVR. Only 57 (30%) of
      191 unoperated patients were evaluated by a cardiac surgeon. There were similar
      rates of intervention across practice settings, and similar rates of unoperated
      patients despite symptoms and low operative risk. CONCLUSIONS: One third of
      patients with severe AS are symptomatic but do not undergo AVR, with similar
      findings in multiple practice environments. For most unoperated patients,
      objectively calculated operative risks did not appear prohibitive. Despite this,
      a minority of unoperated patients were referred for surgical consultation. Some
      patients with severe symptomatic AS may be inappropriately denied access to
      potentially life-saving therapy.

PMID- 20031891
TI  - Patient registries of acute coronary syndrome: assessing or biasing the clinical
      real world data?
AB  - BACKGROUND: The risk of selection bias in registries and its consequences are
      relatively unexplored. We sought to assess selection bias in a recent registry
      about acute coronary syndrome and to explore the way of conducting and reporting
      patient registries of acute coronary syndrome. METHODS AND RESULTS: We analyzed
      data from patients of a national acute coronary syndrome registry undergoing an
      audit about the comprehensiveness of the recruitment/inclusion. Patients
      initially included by hospital investigators (n=3265) were compared to eligible
      nonincluded (missed) patients (n=1439). We assessed, for 25 exposure variables,
      the deviation of the in-hospital mortality relative risks calculated in the
      initial sample from the actual relative risks. Missed patients were of higher
      risk and received less recommended therapies than the included patients. In
      hospital mortality was almost 3 times higher in the missed population (9.34% [95%
      CI, 7.84 to 10.85] versus 3.9% [95% CI, 2.89 to 4.92]). Initial relative risks
      diverged from the actual relative risks more than expected by chance (P<0.05) in
      21 variables, being higher than 10% in 17 variables. This deviation persisted on
      a smaller degree on multivariable analysis. Additionally, we reviewed a sample of
      129 patient registries focused on acute coronary syndrome published in thirteen
      journals, collecting information on good registry performance items. Only in 38
      (29.4%) and 48 (37.2%) registries was any audit of recruitment/inclusion and data
      abstraction, respectively, mentioned. Only 4 (3.1%) authors acknowledged
      potential selection bias because of incomplete recruitment. CONCLUSIONS:
      Irregular inclusion can introduce substantial systematic bias in registries. This
      problem has not been explicitly addressed in a substantial number of them.

PMID- 20031892
TI  - Looking forward, looking back: assessing variations in hospital resource use and
      outcomes for elderly patients with heart failure.
AB  - BACKGROUND: Recent studies have found substantial variation in hospital resource
      use by expired Medicare beneficiaries with chronic illnesses. By analyzing only
      expired patients, these studies cannot identify differences across hospitals in
      health outcomes like mortality. This study examines the association between
      mortality and resource use at the hospital level, when all Medicare beneficiaries
      hospitalized for heart failure are examined. METHODS AND RESULTS: A total of 3999
      individuals hospitalized with a principal diagnosis of heart failure at 6
      California teaching hospitals between January 1, 2001, and June 30, 2005, were
      analyzed with multivariate risk-adjustment models for total hospital days, total
      hospital direct costs, and mortality within 180-days after initial admission
      ("Looking Forward"). A subset of 1639 individuals who died during the study
      period were analyzed with multivariate risk-adjustment models for total hospital
      days and total hospital direct costs within 180-days before death ("Looking
      Back"). "Looking Forward" risk-adjusted hospital means ranged from 17.0% to 26.0%
      for mortality, 7.8 to 14.9 days for total hospital days, and 0.66 to 1.30 times
      the mean value for indexed total direct costs. Spearman rank correlation
      coefficients were -0.68 between mortality and hospital days, and -0.93 between
      mortality and indexed total direct costs. "Looking Back" risk-adjusted hospital
      means ranged from 9.1 to 21.7 days for total hospital days and 0.91 to 1.79 times
      the mean value for indexed total direct costs. Variation in resource use site
      ranks between expired and all individuals were attributable to insignificant
      differences. CONCLUSIONS: California teaching hospitals that used more resources
      caring for patients hospitalized for heart failure had lower mortality rates.
      Focusing only on expired individuals may overlook mortality variation as well as
      associations between greater resource use and lower mortality. Reporting values
      without identifying significant differences may result in incorrect assumption of
      true differences.

PMID- 20031893
TI  - Mortality and readmission for patients with heart failure among U.S. News & World
      Report's top heart hospitals.
AB  - BACKGROUND: The rankings of "America's Best Hospitals" by U.S. News & World
      Report are influential, but the performance of ranked hospitals in caring for
      patients with routine cardiac conditions such as heart failure is not known.
      METHODS AND RESULTS: Using hierarchical regression models based on medical
      administrative data from the period July 1, 2005, to June 30, 2006, we calculated
      risk-standardized mortality rates and risk-standardized readmission rates for
      ranked and nonranked hospitals in the treatment of heart failure. The mortality
      analysis examined 14 813 patients in 50 ranked hospitals and 409 806 patients in
      4761 nonranked hospitals. The readmission analysis included 16 641 patients in 50
      ranked hospitals and 458 473 patients in 4627 nonranked hospitals. Mean 30-day
      risk-standardized mortality rates were lower in ranked versus nonranked hospitals
      (10.1% versus 11.2%, P<0.01), whereas mean 30-day risk-standardized readmission
      rates were no different between ranked and nonranked hospitals (23.6% versus
      23.8%, P=0.40). The 30-day risk-standardized mortality rates varied widely for
      both ranked and nonranked hospitals, ranging from 7.9% to 12.4% for ranked
      hospitals and from 7.1% to 17.5% for nonranked hospitals. The 30-day risk
      standardized readmission rates also spanned a large range, from 18.7% to 29.3%
      for ranked hospitals and from 19.2% to 29.8% for nonranked hospitals.
      CONCLUSIONS: Hospitals ranked by U.S. News & World Report as "America's Best
      Hospitals" in "Heart & Heart Surgery" are more likely than nonranked hospitals to
      have a significantly lower than expected 30-day mortality rate, but there was
      much overlap in performance. For readmission, the rates were similar in ranked
      and nonranked hospitals.

PMID- 20031894
TI  - Cost-consequences of ultrafiltration for acute heart failure: a decision model
      analysis.
AB  - BACKGROUND: Ultrafiltration for heart failure may reduce costs associated with
      acute heart failure by decreasing rehospitalization rates compared to intravenous
      diuretics. METHODS AND RESULTS: We developed a decision-analytic model to explore
      the clinical outcomes and associated costs of ultrafiltration compared to
      intravenous diuretics for index and subsequent acute heart failure
      hospitalizations to 90 days from index hospitalization. We evaluated the model
      from societal, Medicare, and hospital payer perspectives. Base-case probabilities
      and costs were derived from the Ultrafiltration versus Intravenous Diuretics for
      Patients Hospitalized for Acute Decompensated Congestive Heart Failure clinical
      trial, Medicare reimbursement schedules, and published data. From a societal
      perspective, treatment with ultrafiltration had an 86% probability of being more
      expensive than intravenous diuretics in probabilistic sensitivity analysis, with
      a base-case estimate of $13 469 per patient treated with ultrafiltration compared
      to $11 610 per patient treated with intravenous diuretics. Cost estimates were
      most influenced by length of index hospitalization, daily cost of
      rehospitalization, number of days rehospitalized, and number and cost of
      ultrafiltration filters. From a Medicare payer perspective, ultrafiltration had a
      >99% probability of being cost saving. From a hospital perspective, there was a
      97% probability ultrafiltration was more expensive. Our model suggested similar
      90-day mortality rates between treatment arms. CONCLUSIONS: Despite a reduction
      in rehospitalization rates, it is unlikely ultrafiltration results in cost
      savings from a societal perspective. The discordance in cost between societal,
      Medicare, and hospital perspectives underscores the importance of payer
      perspective in formulating strategies and reimbursement structures to reduce
      heart failure hospitalizations.

PMID- 20031895
TI  - Outcomes among patients with ST-segment-elevation myocardial infarction
      presenting to interventional hospitals with and without on-site cardiac surgery.
AB  - BACKGROUND: Primary percutaneous coronary intervention (pPCI) is the preferred
      reperfusion strategy for patients with ST-segment-elevation myocardial infarction
      (STEMI). The quality of care and safety and efficacy of pPCI at hospitals without
      on-site open heart surgery (No-OHS hospitals) remains an area of active
      investigation. METHODS AND RESULTS: The National Registry of Myocardial
      Infarction enrolled 58 821 STEMI patients from 214 OHS hospitals (n=54 076) and
      52 No-OHS hospitals (n=4745) with PCI capabilities from 2004 to 2006. Patients
      presenting to OHS hospitals had substantially lower in-hospital mortality (7.0%
      versus 9.8%, P<0.001) and were more likely to receive any form of acute
      reperfusion therapy (80.8% versus 70.8%, P<0.001). Patients who presented to OHS
      hospitals were more likely to receive guideline recommended medications within 24
      hours of arrival. In a propensity score model matching for patient
      characteristics and transfer status, in-hospital mortality remained significantly
      lower among patients presenting to OHS hospitals (7.2% versus 9.3%, P=0.025).
      When this model was further adjusted for differences in the use of acute
      reperfusion therapy, medications administered within 24 hours and hospital
      characteristics, the mortality difference was of borderline significance (hazard
      ratio, 0.87; 95% CI, 0.75 to 1.01; P=0.067). When the propensity score analysis
      was restricted to patients who underwent pPCI, there was no significant
      difference in mortality (3.8% versus 3.3%, P=0.44). CONCLUSIONS: STEMI patients
      presenting to No-OHS hospitals have substantially higher mortality, are less
      likely to receive guideline recommended medications within 24 hours, and are less
      likely to undergo acute reperfusion therapy, although this difference was of
      borderline significance after adjusting for hospital and treatment variables.
      There was no difference in mortality among patients undergoing pPCI.

PMID- 20031896
TI  - Reoperation for bleeding in patients undergoing coronary artery bypass surgery:
      incidence, risk factors, time trends, and outcomes.
AB  - BACKGROUND: Reoperation for bleeding represents an important complication in
      patients undergoing coronary artery bypass surgery (CABG). Yet, few studies have
      characterized risk factors and patient outcomes of this event. METHODS AND
      RESULTS: We evaluated 528 686 CABG patients at >800 hospitals in the Society of
      Thoracic Surgeons National Cardiac Database (2004 to 2007). Clinical features and
      in-hospital outcomes were evaluated in patients with and without reoperation for
      bleeding after CABG. Logistic regression was used to identify predictors of risk
      of this event and to estimate weights for an additive risk score. A total of 12
      652 CABG patients (2.4%) required reoperation for bleeding. These rates remained
      fairly stable over time (2.2%, 2.3%, 2.5%, and 2.4% from 2004 to 2007,
      respectively). Although overall operative mortality was 4.5-fold higher in
      patients requiring reoperation for bleeding versus those who did not (2.0% versus
      9.1%), this mortality risk declined significantly over time (11.3%, 9.5%, 8.8%,
      and 8.2% from 2004 to 2007, respectively, P for trend=0.0006). Factors associated
      with higher risk for reoperation were identified by multivariable analysis (c
      statistic=0.60) and summarized into a simple bedside risk score. The risk-score
      performed well when tested in the validation set (Hosmer-Lemeshow P=0.16).
      CONCLUSIONS: Reoperation for bleeding remains an important morbid event after
      CABG. Nonetheless, death in patients with this complication has decreased over
      time. Our risk tool should allow estimation of patients risk for reoperation for
      bleeding and promote preventive measures when feasible in this at-risk group.

PMID- 20031897
TI  - Epidemiology of subtherapeutic anticoagulation in the United States.
AB  - BACKGROUND: Low international normalized ratio (INR; <or=1.5) increases risk for
      thromboembolism. However, little is known about the epidemiology of low INR.
      METHODS AND RESULTS: We prospectively collected data from 47 community-based
      clinics located throughout the United States from 2000 to 2002. We examined risk
      factors for low INR (<or=1.5), reasons given in the medical record for low INR,
      and proportion of thromboembolic events that occurred during periods of low INR.
      Of the 4489 patients in our database, 1540 (34%) had at least 1 low INR. Compared
      with men, women had an increased incidence of low INR (adjusted incidence rate
      ratio, 1.44; P<0.001). Compared with patients anticoagulated for atrial
      fibrillation, patients anticoagulated for venous thromboembolism had an increased
      incidence of low INR (adjusted incidence rate ratio, 1.48; P<0.001). The 5 most
      common reasons for low INR were nonadherence (17%), interruptions for procedures
      (16%), recent dose reductions (15%), no reason apparent after questioning (15%),
      and second or greater consecutive low INR (13%). A total of 21.8% of
      thromboembolic events (95% CI, 12.2 to 35.4%) occurred during periods of low INR;
      58% of these events were related to an interruption of warfarin therapy.
      CONCLUSIONS: In this cohort of patients receiving warfarin, more than 1 in 5
      thromboembolic events occurred during a period of low INR. Women and patients
      anticoagulated for venous thromboembolism were particularly likely to experience
      low INR. Improving adherence, minimizing interruptions of therapy, and addressing
      low INR more promptly could reduce the risk of low INR.

PMID- 20031898
TI  - Would achieving healthy people 2010's targets reduce both population levels and
      social disparities in heart disease?
AB  - BACKGROUND: The US Healthy People 2010 (HP2010) agenda set targets for major risk
      factors for coronary heart disease (CHD). However, the potential impact of
      achieving those risk factor reductions on both population levels and social
      disparities in CHD has not been quantified. METHODS AND RESULTS: Data on 10-year
      risk of CHD (from the First National Health and Nutrition Examination
      Epidemiological Follow-Up study 1971 to 1982), prevalence of major CHD risk
      factors (from the National Health and Nutrition Examination Survey 2003 to 2004),
      and HP2010 targets for CHD risk factors (reduction of smoking rate to 12%,
      hypertension to 14%, high cholesterol levels to 17%, diabetes to 2.5%, and
      obesity to 15%) were used to estimate effects of different scenarios on
      population levels and social disparities in CHD. Over a 10-year period, the
      largest relative reductions in population levels of CHD (20.0% in men; 23.9% in
      women) would be achieved if all social groups met the HP2010 targets. CHD
      disparities would be most reduced if the less educated (absolute disparities
      reduced by 66.1% in men; 56.3% in women) and the low income group (absolute
      disparities reduced by 93.7% in men; 94.3% in women) achieved the targets before
      the most advantaged. These reductions are larger than those expected if targets
      were achieved overall for the population but relative social group differences in
      risk factors remained, or under leveling-up approaches in which the least
      advantaged achieved the current levels of risk factors of the most advantaged.
      CONCLUSIONS: Interventions to reduce CHD risk factors to HP2010 targets that
      focus on all social groups would produce the best overall scenario for both
      population levels and disparities in CHD.

PMID- 20031900
TI  - Number needed to treat with rosuvastatin to prevent first cardiovascular events
      and death among men and women with low low-density lipoprotein cholesterol and
      elevated high-sensitivity C-reactive protein: justification for the use of
      statins in prevention: an intervention trial evaluating rosuvastatin (JUPITER).
AB  - BACKGROUND: As recently demonstrated, random allocation to rosuvastatin results
      in large relative risk reductions for first cardiovascular events among
      apparently healthy men and women with low levels of low-density lipoprotein
      cholesterol but elevated levels of high-sensitivity C-reactive protein. However,
      whether the absolute risk reduction among such individuals justifies wide
      application of statin therapy in primary prevention is a controversial issue with
      broad policy and public health implications. METHODS AND RESULTS: Absolute risk
      reductions and consequent number needed to treat (NNT) values were calculated
      across a range of end points, timeframes, and subgroups using data from
      Justification for the Use of statins in Prevention: an Intervention Trial
      Evaluating Rosuvastatin (JUPITER), a randomized evaluation of rosuvastatin 20 mg
      versus placebo conducted among 17 802 apparently healthy men and women with low
      density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive
      protein >or=2 mg/L. Sensitivity analyses were also performed to address the
      potential impact that alternative statin regimens might have on a similar primary
      prevention population. For the end point of myocardial infarction, stroke,
      revascularization, or death, the 5-year NNT within JUPITER was 20 (95% CI, 14 to
      34). All subgroups had 5-year NNT values for this end point below 50; as
      examples, 5-year NNT values were 17 for men and 31 for women, 21 for whites and
      19 for nonwhites, 18 for those with body mass index <or=25 kg/m(2) and 21 for
      those with body mass index greater than 25 kg/m(2), 9 and 26 for those with and
      without a family history of coronary disease, 19 and 22 for those with and
      without metabolic syndrome, and 14 and 37 for those with estimated Framingham
      risks greater or less than 10%. For the net vascular benefit end point that
      additionally included venous thromboembolism, the 5-year NNT was 18 (95% CI, 13
      to 29). For the restricted "hard" end point of myocardial infarction, stroke, or
      death, the 5-year NNT was 29 (95% CI, 19 to 56). In sensitivity analyses
      addressing the theoretical utility of alternative agents, 5-year NNT values of 38
      and 57 were estimated for statin regimens that deliver 75% and 50% of the
      relative benefit observed in JUPITER, respectively. All of these calculations
      compare favorably to 5-year NNT values previously reported in primary prevention
      for the use of statins among hyperlipidemic men (5-year NNT, 40 to 70), for
      antihypertensive therapy (5-year NNT, 80 to 160), or for aspirin (5-year NNT,
      >300). CONCLUSIONS: Absolute risk reductions and consequent NNT values associated
      with statin therapy among those with elevated high-sensitivity C-reactive protein
      and low low-density lipoprotein cholesterol are comparable if not superior to
      published NNT values for several widely accepted interventions for primary
      cardiovascular prevention, including the use of statin therapy among those with
      overt hyperlipidemia. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. Identifier
      NCT00239681.

PMID- 20031901
TI  - Effect of endovascular aneurysm repair on the volume-outcome relationship in
      aneurysm repair.
AB  - BACKGROUND: We aim to quantify the relationship between the annual caseload
      (volume) and outcome from elective endovascular (EVR) or open repair of abdominal
      aortic aneurysms (AAAs) in England between 2005 and 2007. METHODS AND RESULTS:
      Individual patient data were obtained from the Hospital Episode Statistics.
      Statistical methods included multiple logistic regression models, mortality
      control charts, and safety plots to determine the nature of any relationship
      between volume and outcome. The case-mix between hospitals of different sizes was
      examined using observed and expected values for in-hospital mortality. Outcome
      measures included in-hospital mortality and hospital length of stay. Between 2005
      and 2007, a total of 57 587 patients were admitted to hospitals in England with a
      diagnosis of AAA, and 11 574 underwent AAA repair. There were 7313 elective AAA
      repairs, of which 5668 (78%) were open and 1645 (22%) were EVR. In-hospital
      mortality rates were 5.63% for all elective AAA repairs with rates of 6.18% for
      open repair and 3.77% for EVR (odds ratio, 0.676; 95% CI, 0.501 to 0.913;
      P=0.011). High-volume aneurysm services were associated with significantly lower
      mortality rates overall (0.991; 0.988 to 0.994; P<0.0001), for open repairs
      (0.994; 0.991 to 0.998; P=0.0008), and EVR (0.989; 0.982 to 0.995; P=0.0007).
      Large endovascular units had low mortality rates for open repairs. CONCLUSIONS: A
      strong relationship existed between the volume of surgery performed and outcome
      from both open and endovascular aneurysm repairs. These data support the concept
      that abdominal aortic surgery should be performed in specialized units that meet
      a minimum volume threshold.

PMID- 20031899
TI  - Temporal trends in patient-reported angina at 1 year after percutaneous coronary
      revascularization in the stent era: a report from the National Heart, Lung, and
      Blood Institute-sponsored 1997-2006 dynamic registry.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) has witnessed rapid
      technological advancements, resulting in improved safety and effectiveness over
      time. Little, however, is known about the temporal impact on patient-reported
      symptoms and quality of life after PCI. METHODS AND RESULTS: Temporal trends in
      post-PCI symptoms were analyzed using 8879 consecutive patients enrolled in the
      National Heart, Lung, and Blood Institute-sponsored Dynamic Registry (wave 1:
      1997 [bare metal stents], wave 2: 1999 [uniform use of stents], wave 3: 2001
      [brachytherapy], wave 4, 5: 2004, 2006 [drug eluting stents]). Patients
      undergoing PCI in the recent waves were older and more often reported
      comorbidities. However, fewer patients across the waves reported post-PCI angina
      at one year (wave 1 to 5: 24%, 23%, 18%, 20%, 20%; P(trend)<0.001). The lower
      risk of angina in recent waves was explained by patient characteristics including
      use of antianginal medications at discharge (relative risk [95% CI] for waves 2,
      3, 4 versus 1: 1.0 [0.9 to 1.2], 0.9 [0.7 to 1.1], 1.0 [0.8 to 1.3], 0.9 [0.7 to
      1.1]). Similar trend was seen in the average quality of life scores over time
      (adjusted mean score for waves 1 to 5: 6.2, 6.5, 6.6 and 6.6; P(trend)=0.01).
      Other factors associated with angina at 1 year included younger age, female
      gender, prior revascularization, need for repeat PCI, and hospitalization for
      myocardial infarction over 1 year. CONCLUSIONS: Favorable temporal trends are
      seen in patient-reported symptoms after PCI in routine clinical practice.
      Specific subgroups, however, remain at risk for symptoms at 1 year and thus
      warrant closer attention.

PMID- 20031902
TI  - Trends in the use of evidence-based treatments for coronary artery disease among
      women and the elderly: findings from the get with the guidelines quality
      improvement program.
AB  - BACKGROUND: Significant disparities have been reported in the application of
      evidence-based guidelines in the treatment of coronary artery disease (CAD) in
      women and the elderly. We hypothesized that participation in a quality
      improvement program could improve care for all patients and thus narrow treatment
      gaps over time. METHODS AND RESULTS: Treatment of 237 225 patients hospitalized
      with CAD was evaluated in the Get With the Guidelines-CAD program from 2002 to
      2007. Six quality measures were evaluated in eligible patients without
      contraindications: aspirin on admission and discharge, beta-blockers use at
      discharge, angiotensin-converting enzyme inhibitor or angiotensin receptor
      antagonist use, lipid-lowering medication use, and tobacco cessation counseling
      along with other care metrics. Over time, composite adherence on these 6 measures
      increased from 86.5% to 97.4% (+10.9%) in men and 84.8% to 96.2% (+11.4%) in
      women. There was a slight difference in composite adherence by sex that remained
      significant over time (P<0.0001), but this was confined to patients <75 years.
      Composite adherence in younger patients (<75 years) increased from 87.1% to 97.7%
      (+10.6%) and from 83.0% to 95.1% (+12.1%) in the elderly (>or=75 years) over
      time. CONCLUSIONS: Among hospitals participating in Get With the Guidelines-CAD,
      guideline adherence has improved substantially over time for both women and men
      and younger and older CAD patients, with only slight age and sex differences in
      some measures persisting.

PMID- 20031903
TI  - Complication rates after left- versus right-sided carotid endarterectomy.
AB  - BACKGROUND: Studies suggest that the side of carotid endarterectomy (CE) may
      influence the rate of postoperative complications. We sought to clarify this by
      (1) analysis of individual-level data from 3 large studies and (2) systematic
      review and meta-analysis of additional published descriptions of outcomes by
      side. METHODS AND RESULTS: The Western Canada Carotid Endarterectomy (WCCE) study
      (n=3164) was analyzed for outcomes by side along with data from the North
      American Symptomatic Carotid Endarterectomy Trial (NASCET; n=1415), and the ASA
      [Acetylsalicylic Acid] in Carotid Endarterectomy Trial (ACE; n=2469). Pooled
      analysis of individual-level data from these three studies allowed calculation of
      rate ratios for stroke or death by side. Medline and EMBASE were searched to
      identify additional studies reporting CE outcomes by side, and an overall risk
      ratio for outcomes by side was determined with fixed-effects meta-analysis. The
      WCCE in-hospital stroke or death rates for left and right-sided CE were 3.72% and
      3.07%, respectively (P=0.27). A pooled analysis of the NASCET and ACE trials also
      revealed higher stroke or death rates for left-sided CE (5.39% versus 2.96%;
      P<0.001). The corresponding risk-adjusted rate ratios for stroke or death for
      left- versus right-sided surgery were 1.22 (95% CI, 0.83 to 1.77) for WCCE and
      1.82 (1.32 to 2.50) for the pooled NASCET and ACE trials. Systematic review of
      the literature identified 2 additional studies. Meta-analysis of all 5 available
      studies yielded a corresponding pooled rate ratio for stroke or death of 1.36
      (1.18 to 1.56). CONCLUSIONS: Left-sided CE is consistently associated with higher
      postoperative adverse event rates. Research into potential mechanisms is required
      to explain and address this finding.

PMID- 20031904
TI  - ST-elevation myocardial infarction: which patients do quality assurance programs
      include?
AB  - BACKGROUND: In the United States, efforts are underway to improve timely access
      to percutaneous coronary intervention in ST-elevation myocardial infarction
      (STEMI). The Joint Commission (TJC) and the American College of Cardiology
      National Cardiovascular Data Registry (NCDR) have developed standardized
      definitions and clinical performance measures for STEMI. The purpose of this
      study was to determine differences in 3 quality-assurance registries for STEMI
      patients. METHODS AND RESULTS: STEMI patients presenting to the Minneapolis Heart
      Institute at Abbott Northwestern Hospital (Minneapolis, Minn) are tracked by 3
      distinct quality assurance programs: NCDR, TJC, and the level 1 MI registry (a
      regional system for percutaneous coronary intervention in STEMI which includes
      transfer patients). Over 1 year, we examined consecutive STEMI patients in level
      1 and compared them with individuals meeting NCDR and TJC inclusion criteria. Of
      501 STEMI patients treated using the level 1 MI protocol, 422 patients had a
      clear culprit (402 percutaneous coronary intervention, 13 coronary artery bypass
      grafting, 7 medical management). In the same period, 282 patients met inclusion
      criteria for NCDR (56% of the level 1 population), and 66 met inclusion criteria
      for TJC (13% of the level 1 population). Transfer patients (n=380) accounted for
      87% of the discrepancy between level 1 and TJC. Pharmacoinvasive percutaneous
      coronary intervention (n=102) accounted for 47% of the discrepancy between level
      1 and NCDR. CONCLUSIONS: Current inclusion criteria for enrollment in STEMI
      registries are not uniform. This may lead to variable quality assurance outcomes
      for the same patient cohort and has important implications for standardized
      quality measurement.

PMID- 20031905
TI  - Neutrophilia predicts death and heart failure after myocardial infarction: a
      community-based study.
AB  - BACKGROUND: The relationship between neutrophils and outcomes post-myocardial
      infarction (MI) is not completely characterized. We examined the associations of
      neutrophil count with mortality and post-MI heart failure (HF) and their
      incremental value for risk discrimination in the community. METHODS AND RESULTS:
      MI was diagnosed with cardiac pain, biomarkers, and Minnesota coding of the ECG.
      Neutrophil count at presentation, reported as counts x10(9)/L, was categorized by
      tertiles (lower tertile, <5.7; middle tertile, 5.7 to 8.5; upper tertile, >8.5).
      From 1979 to 2002, 2047 incident MIs occurred in Olmsted County, Minn (mean age,
      68+/-14 years; 44% women). Median (25th to 75th percentile) neutrophil count was
      7.0 (5.1 to 9.5). Within 3 years post-MI, 577 patients died, and 770 developed
      HF. Overall survival and survival free of HF decreased with increased neutrophil
      tertile (P<0.001). Compared with the lower tertile, the age and sex adjusted
      hazard ratio for death was 1.44 (95% CI, 1.14 to 1.81) for the middle tertile and
      2.60 (95% CI, 2.10 to 3.22) for the upper tertile (P<0.001). Similarly, for HF,
      the hazard ratio was 1.32 (95% CI, 1.09 to 1.59) for the middle and 2.12 (95% CI,
      1.77 to 2.53) for the upper tertile (P<0.001). These associations persisted after
      adjustment for risk factors, comorbidities, Killip class, revascularization, and
      ejection fraction. Neutrophil count improved risk discrimination as indicated by
      increases in the area under the receiver operating characteristic curves (all
      P<0.05) and by the integrated discrimination improvement analysis (all P<0.001).
      CONCLUSIONS: In the community, the neutrophil count was strongly and
      independently associated with death and HF post-MI and improved risk
      discrimination over traditional predictors.

PMID- 20031907
TI  - Percutaneous coronary intervention outcomes in a low-volume center: survival,
      stent thrombosis, and repeat revascularization.
AB  - BACKGROUND: American College of Cardiology (ACC) guidelines state that
      percutaneous coronary interventions (PCI) be performed at centers and by
      operators with high-volume (>400 yearly/center) whose historical and current risk
      adjusted outcomes statistics are comparable to those reported in large
      registries. Tripler Army Medical Center is a low-volume treatment facility but
      has a geographic need and special mission requirement for providing this service.
      METHODS AND RESULTS: We computed 30-day incidence of stent thrombosis, need for
      repeat revascularization, and all-cause mortality for all PCIs performed at
      Tripler from January 2002 through June 2008. The New York State Registry
      regression model was selected among 3 risk-adjustment models that we assessed in
      our patients. This model was used to compute expected mortality rate based on
      patient risk factors. The 30-day incidence of stent thrombosis and repeat
      revascularization was also determined, and the long-term incidence of these
      events was estimated with the Kaplan-Meier method as was survival. For all 546
      PCI procedures, 30-day mortality was 1.47%, the incidence of stent thrombosis
      2.1%, the incidence of any repeat revascularization 5.1%, and the combined event
      rate 5.9%. Based on risk factors used in the New York State Registry, our
      expected mortality was 1.93% and not significantly different from the observed
      rate. Although survival at 1 and 3 years appeared comparable with benchmarks at
      94.6% and 89.3%, as did repeat revascularization rates at 13.0% and 21.4%, the
      incidence of stent thrombosis was regarded as high whether the definition
      included possible cases (3.2% and 3.9%) or only those regarded as definite or
      probable (2.7% and 3.1%). We did not identify any remediable risk factors for
      stent thrombosis, nor were we able to identify significant differences by year or
      by operator. However, visual inspection of a plot of deciles of New York State
      risk of death demonstrated 2 outlier cases among the 8 who died, who could have
      been considered candidates for thorough peer review. CONCLUSIONS: We recommend
      other low-volume interventional programs enter all patients undergoing PCI into a
      database, their own local registry even if not a national one such as the
      American College of Cardiology National Cardiovascular Data Registry, obtain
      information about survival and cardiac events during follow-up, compute and risk
      adjust in-hospital or 30-day mortality, and use the objective assessment of risk
      in individual patients to identify outliers when outcome is adverse, and possibly
      as a means of triaging patients to appropriate therapy before choosing PCI.

PMID- 20031906
TI  - Vision and creation of the American Heart Association pharmaceutical roundtable
      outcomes research centers.
AB  - BACKGROUND: The field of outcomes research seeks to define optimal treatment in
      practice and to promote the rapid full adoption of efficacious therapies into
      routine clinical care. The American Heart Association (AHA) formed the AHA
      Pharmaceutical Roundtable (PRT) Outcomes Research Centers Network to accelerate
      attainment of these goals. Participating centers were intended to carry out state
      of-the-art outcomes research in cardiovascular disease and stroke, to train the
      next generation of investigators, and to support the formation of a collaborative
      research network. PROGRAM: After a competitive application process, 4 AHA PRT
      Outcomes Research Centers were selected: Duke Clinical Research Institute; Saint
      Luke's Mid America Heart Institute; Stanford University-Kaiser Permanente of
      Northern California; and University of California, Los Angeles. Each center
      proposed between 1 and 3 projects organized around a single theme in
      cardiovascular disease or stroke. Additionally, each center will select and train
      up to 6 postdoctoral fellows over the next 4 years, and will participate in cross
      collaborative activities among the centers. CONCLUSIONS: The AHA PRT Outcomes
      Research Centers Network is designed to further strengthen the field of
      cardiovascular disease and stroke outcomes research by fostering innovative
      research, supporting high quality training, and encouraging center-to-center
      collaborations.

PMID- 20031908
TI  - Training programs in outcomes research: the "field guide" for current
      opportunities.

PMID- 20031909
TI  - Mis-SHAPEing public health policy.

PMID- 20031910
TI  - In the light of day: plant photomorphogenesis.

PMID- 20031911
TI  - Chemically induced and light-independent cryptochrome photoreceptor activation.
AB  - The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N
      terminal photosensory domain mediates dimerization, and the unique C-terminal
      extension (CCT) mediates signaling. We made use of the human FK506-binding
      protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs
      (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB,
      thus allowing rapamycin-induced dimerization of two target proteins. Here we
      demonstrate by bioluminescence resonance energy transfer (BRET) assays the
      applicability of this regulated dimerization system to plants. Furthermore, we
      show that fusion proteins consisting of the C-terminal domain of Arabidopsis
      cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells
      specifically induce the expression of cryptochrome-controlled reporter and
      endogenous genes in darkness upon incubation with the rapalog. These results
      demonstrate that the activation of cryptochrome signal transduction can be
      chemically induced in a dose-dependent fashion and uncoupled from the light
      signal, and provide the groundwork for gain-of-function experiments to study
      specifically the role of photoreceptors in darkness or in signaling cross-talk
      even under light conditions that activate members of all photoreceptor families.

PMID- 20031912
TI  - Leaf positioning of Arabidopsis in response to blue light.
AB  - Appropriate leaf positioning is essential for optimizing photosynthesis and plant
      growth. However, it has not been elucidated how green leaves reach and maintain
      their position for capturing light. We show here the regulation of leaf
      positioning under blue light stimuli. When 1-week-old Arabidopsis seedlings grown
      under white light were transferred to red light (25 micromol m(-2) s(-1)) for 5
      d, new petioles that appeared were almost horizontal and their leaves were curled
      and slanted downward. However, when a weak blue light from above (0.1 micromol m(
      2) s(-1)) was superimposed on red light, the new petioles grew obliquely upward
      and the leaves were flat and horizontal. The leaf positioning required both
      phototropin1 (phot1) and nonphototropic hypocotyl 3 (NPH3), and resulted in
      enhanced plant growth. In an nph3 mutant, neither optimal leaf positioning nor
      leaf flattening by blue light was found, and blue light-induced growth
      enhancement was drastically reduced. When blue light was increased from 0.1 to 5
      micromol m(-2) s(-1), normal leaf positioning and leaf flattening were induced in
      both phot1 and nph3 mutants, suggesting that phot2 signaling became functional
      and that the signaling was independent of phot1 and NPH3 in these responses. When
      plants were irradiated with blue light (0.1 micromol m(-2) s(-1)) from the side
      and red light from above, the new leaves became oriented toward the source of
      blue light. When we transferred these plants to both blue light and red light
      from above, the leaf surface changed its orientation to the new blue light source
      within a few hours, whereas the petioles initially were unchanged but then
      gradually rotated, suggesting the plasticity of leaf positioning in response to
      blue light. We showed the tissue expression of NPH3 and its plasma membrane
      localization via the coiled-coil domain and the C-terminal region. We conclude
      that NPH3-mediated phototropin signaling optimizes the efficiency of light
      perception by inducing both optimal leaf positioning and leaf flattening, and
      enhances plant growth.

PMID- 20031913
TI  - Role of Arabidopsis RAP2.4 in regulating light- and ethylene-mediated
      developmental processes and drought stress tolerance.
AB  - Light and the plant hormone ethylene regulate many aspects of plant growth and
      development in an overlapping and interdependent fashion. Little is known
      regarding how their signal transduction pathways cross-talk to regulate plant
      development in a coordinated manner. Here, we report functional characterization
      of an AP2/DREB-type transcription factor, Arabidopsis RAP2.4, in mediating light
      and ethylene signaling. Expression of the RAP2.4 gene is down-regulated by light
      but up-regulated by salt and drought stresses. RAP2.4 protein is constitutively
      targeted to the nucleus and it can bind to both the ethylene-responsive GCC-box
      and the dehydration-responsive element (DRE). We show that RAP2.4 protein
      possesses an intrinsic transcriptional activation activity in yeast cells and
      that it can activate a reporter gene driven by the DRE cis-element in Arabidopsis
      protoplasts. Overexpression of RAP2.4 or mutation in RAP2.4 cause altered
      expression of representative light-, ethylene-, and drought-responsive genes.
      Although no salient phenotype was observed with a rap2.4 loss-of-function mutant,
      constitutive overexpression of RAP2.4 results in defects in multiple
      developmental processes regulated by light and ethylene, including hypocotyl
      elongation and gravitropism, apical hook formation and cotyledon expansion,
      flowering time, root elongation, root hair formation, and drought tolerance.
      Based on these observations, we propose that RAP2.4 acts at or downstream of a
      converging point of light and ethylene signaling pathways to coordinately
      regulate multiple developmental processes and stress responses.

PMID- 20031914
TI  - The clock protein CCA1 and the bZIP transcription factor HY5 physically interact
      to regulate gene expression in Arabidopsis.
AB  - The circadian clock regulates the expression of an array of Arabidopsis genes
      such as those encoding the LIGHT-HARVESTING CHLOROPHYLL A/B (Lhcb) proteins. We
      have previously studied the promoters of two of these Arabidopsis genes--Lhcb1*1
      and Lhcb1*3--and identified a sequence that binds the clock protein CIRCADIAN
      CLOCK ASSOCIATED 1 (CCA1). This sequence, designated CCA1-binding site (CBS), is
      necessary for phytochrome and circadian responsiveness of these genes. In close
      proximity to this sequence, there exists a G-box core element that has been shown
      to bind the bZIP transcription factor HY5 in other light-regulated plant
      promoters. In the present study, we examined the importance of the interaction of
      transcription factors binding the CBS and the G-box core element in the control
      of normal circadian rhythmic expression of Lhcb genes. Our results show that HY5
      is able to specifically bind the G-box element in the Lhcb promoters and that
      CCA1 can alter the binding activity of HY5. We further show that CCA1 and HY5 can
      physically interact and that they can act synergistically on transcription in a
      yeast reporter gene assay. An absence of HY5 leads to a shorter period of Lhcb1*1
      circadian expression but does not affect the circadian expression of CATALASE3
      (CAT3), whose promoter lacks a G-box element. Our results suggest that
      interaction of the HY5 and CCA1 proteins on Lhcb promoters is necessary for
      normal circadian expression of the Lhcb genes.

PMID- 20031915
TI  - Evidence of a light-sensing role for folate in Arabidopsis cryptochrome blue
      light receptors.
AB  - Arabidopsis cryptochromes cry1 and cry2 are blue-light signalling molecules with
      significant structural similarity to photolyases--a class of blue-light-sensing
      DNA repair enzymes. Like photolyases, purified plant cryptochromes have been
      shown to bind both flavin and pterin chromophores. The flavin functions as a
      light sensor and undergoes reduction in response to blue light that initiates the
      signalling cascade. However, the role of the pterin in plant cryptochromes has
      until now been unknown. Here, we show that the action spectrum for light
      dependent degradation of cry2 has a significant peak of activity at 380 nm,
      consistent with absorption by a pterin cofactor. We further show that cry1
      protein expressed in living insect cells responds with greater sensitivity to 380
      nm light than to 450 nm, consistent with a light-harvesting antenna pigment that
      transfers excitation energy to the oxidized flavin of cry1. The pterin
      biosynthesis inhibitor DHAP selectively reduces cryptochrome responsivity at 380
      nm but not 450 nm blue light in these cell cultures, indicating that the antenna
      pigment is a folate cofactor similar to that of photolyases.

PMID- 20031916
TI  - Abscisic acid, high-light, and oxidative stress down-regulate a photosynthetic
      gene via a promoter motif not involved in phytochrome-mediated transcriptional
      regulation.
AB  - In etiolated seedlings, light perceived by phytochrome promotes the expression of
      light-harvesting chlorophyll a/b protein of photosystem II (Lhcb) genes. However,
      excess of photosynthetically active radiation can reduce Lhcb expression. Here,
      we investigate the convergence and divergence of phytochrome, high-light stress
      and abscisic acid (ABA) signaling, which could connect these processes. Etiolated
      Arabidopsis thaliana seedlings bearing an Lhcb promoter fused to a reporter were
      exposed to continuous far-red light to activate phytochrome and not
      photosynthesis, and treated with ABA. We identified a cis-acting region of the
      promoter required for down-regulation by ABA. This region contains a CCAC
      sequence recently found to be necessary for ABI4-binding to an Lhcb promoter.
      However, we did not find a G-box-binding core motif often associated with the
      ABI4-binding site in genes promoted by light and repressed by ABI4. Mutations
      involving this motif also impaired the responses to reduced water potential, the
      response to high photosynthetic light and the response to methyl viologen but not
      the response to low temperature or to Norflurazon. We propose a model based on
      current and previous findings, in which hydrogen peroxide produced in the
      chloroplasts under high light conditions interacts with the ABA signaling network
      to regulate Lhcb expression. Since the mutation that affects high-light and
      methyl viologen responses does not affect phytochrome-mediated responses, the
      regulation by retrograde and phytochrome signaling can finally be separated at
      the target promoter level.

PMID- 20031917
TI  - A rice phytochrome A in Arabidopsis: The Role of the N-terminus under red and far
      red light.
AB  - The phytochrome (phy)A and phyB photoreceptors mediate three photobiological
      response modes in plants; whereas phyA can mediate the very-low-fluence response
      (VLFR), the high-irradiance response (HIR) and, to some extent, the low fluence
      response (LFR), phyB and other type II phytochromes only mediate the LFR. To
      investigate to what level a rice phyA can complement for Arabidopsis phyA or phyB
      function and to evaluate the role of the serine residues in the first 20 amino
      acids of the N-terminus of phyA, we examined VLFR, LFR, and HIR responses in phyB
      and phyAphyB mutant plants transformed with rice PHYA cDNA or a mutant rice PHYA
      cDNA in which the first 10 serine residues were mutated to alanines (phyA SA).
      Utilizing mutants without endogenous phyB allowed the evaluation of red-light
      derived responses sensed by the rice phyA. In summary, the WT rice phyA could
      complement VLFR and LFR responses such as inhibition of hypocotyl elongation
      under pulses of FR or continuous R light, induction of flowering and leaf
      expansion, whereas the phyA SA was more specific for HIR responses (e.g.
      inhibition of hypocotyl elongation and anthocyanin accumulation under continuous
      far-red light). As the N-terminal serines can no longer be phosphorylated in the
      phyA SA mutant, this suggests a role for phosphorylation discriminating between
      the different phyA-dependent responses. The efficacy of the rice phyA expressed
      in Arabidopsis was dependent upon the developmental age of the plants analyzed
      and on the physiological response, suggesting a stage-dependent downstream
      modulation of phytochrome signaling.

PMID- 20031918
TI  - The subcellular localization and blue-light-induced movement of phototropin 1-GFP
      in etiolated seedlings of Arabidopsis thaliana.
AB  - Phototropin 1 (phot1) is a photoreceptor for phototropism, chloroplast movement,
      stomatal opening, leaf expansion, and solar tracking in response to blue light.
      Following earlier work with PHOT1::GFP (Sakamoto and Briggs, 2002), we
      investigated the pattern of cellular and subcellular localization of phot1 in 3-
      4-d-old etiolated seedlings of Arabidopsis thalinana. As expressed from native
      upstream sequences, the PHOT1::GFP fusion protein is expressed strongly in the
      abaxial tissues of the cotyledons and in the elongating regions of the hypocotyl.
      It is moderately expressed in the shoot/root transition zone and in cells near
      the root apex. A fluorescence signal is undetectable in the root epidermis, root
      cap, and root apical meristem itself. The plasma membranes of mesophyll cells
      near the cotyledon margin appear labeled uniformly but cross-walls created by
      recent cell divisions are more strongly labeled. The pattern of labeling of
      individual cell types varies with cell type and developmental stage. Blue-light
      treatment causes PHOT1::GFP, initially relatively evenly distributed at the
      plasma membrane, to become reorganized into a distinct mosaic with strongly
      labeled punctate areas and other areas completely devoid of fluorescence--a
      phenomenon best observed in cortical cells in the hypocotyl elongation region.
      Concomitant with or following this reorganization, PHOT1::GFP moves into the
      cytoplasm in all cell types investigated except for guard cells. It disappears
      from the cytoplasm by an unidentified mechanism after several hours in darkness.
      Neither its appearance in the cytoplasm nor its eventual disappearance in
      darkness is prevented by the translation inhibitor cycloheximide, although the
      latter process is retarded. We hypothesize that blue-light-induced phot1 re
      localization modulates blue-light-activated signal transduction.

PMID- 20031919
TI  - Interaction of the Arabidopsis UV-B-specific signaling component UVR8 with
      chromatin.
AB  - Arabidopsis UV RESISTANCE LOCUS8 (UVR8) is a UV-B-specific signaling component
      that regulates expression of a range of genes concerned with UV protection. Here,
      we investigate the interaction of UVR8 with chromatin. Using antibodies specific
      to UVR8 in chromatin immunoprecipitation (ChIP) assays with wild-type plants, we
      show that native UVR8 binds to chromatin in vivo. Similar experiments using an
      anti-GFP antibody with plants expressing a GFP-UVR8 fusion show that UVR8
      associates with a relatively small region of chromatin containing the HY5 gene.
      UVR8 interacts with chromatin containing the promoter regions of other genes, but
      not with all the genes it regulates. UV-B is not required for the interaction of
      UVR8 with chromatin because association with several gene loci is observed in the
      absence of UV-B. Pull-down assays demonstrate that UVR8 associates with histones
      in vivo and competition experiments indicate that the interaction is
      preferentially with histone H2B. ChIP experiments using antibodies that recognize
      specific histone modifications indicate that the UV-B-stimulated transcription of
      some genes may be correlated with histone modification. In particular, the ELIP1
      promoter showed a significant enrichment of diacetyl histone H3 (K9/K14)
      following UV-B exposure. These findings increase understanding of the interaction
      of the key UV-B-specific regulator UVR8 with chromatin.

PMID- 20031920
TI  - Disruptions in AUX1-dependent auxin influx alter hypocotyl phototropism in
      Arabidopsis.
AB  - Phototropism represents a differential growth response by which plant organs can
      respond adaptively to changes in the direction of incident light to optimize
      leaf/stem positioning for photosynthetic light capture and root growth
      orientation for water/nutrient acquisition. Studies over the past few years have
      identified a number of components in the signaling pathway(s) leading to
      development of phototropic curvatures in hypocotyls. These include the
      phototropin photoreceptors (phot1 and phot2) that perceive directional blue-light
      (BL) cues and then stimulate signaling, leading to relocalization of the plant
      hormone auxin, as well as the auxin response factor NPH4/ARF7 that responds to
      changes in local auxin concentrations to directly mediate expression of genes
      likely encoding proteins necessary for development of phototropic curvatures.
      While null mutations in NPH4/ARF7 condition an aphototropic response to
      unidirectional BL, seedlings carrying the same mutations recover BL-dependent
      phototropic responsiveness if co-irradiated with red light (RL) or pre-treated
      with either ethylene. In the present study, we identify second-site enhancer
      mutations in the nph4 background that abrogate these recovery responses. One of
      these mutations--map1 (modifier of arf7 phenotypes 1)--was found to represent a
      missense allele of AUX1--a gene encoding a high-affinity auxin influx carrier
      previously associated with a number of root responses. Pharmacological studies
      and analyses of additional aux1 mutants confirmed that AUX1 functions as a
      modulator of hypocotyl phototropism. Moreover, we have found that the strength of
      dependence of hypocotyl phototropism on AUX1-mediated auxin influx is directly
      related to the auxin responsiveness of the seedling in question.

PMID- 20031921
TI  - Analysis of natural allelic variation controlling Arabidopsis thaliana seed
      germinability in response to cold and dark: identification of three major
      quantitative trait loci.
AB  - Light and temperature are key external factors in the control of Arabidopsis
      thaliana seed germination and dormancy mechanisms. Perception and response to
      these stimuli have to ensure that seedling emergence and growth occur at the most
      advantageous time for correct establishment. Analysis of over 300 Arabidopsis
      accessions identified 14, from 12 different geographical locations, that were
      able to germinate to greater than 20% at 6 degrees C in the dark. This natural
      variation was exploited to identify genetic loci responsible for cold-tolerant,
      dark germination. A quantitative trait loci approach was used on recombinant
      inbred line progeny of a cross between Bay-0 and Shahdara. Six distinct
      quantitative trait loci were identified, three of which were major loci, each
      responsible for 17-25% of the phenotypic variability in this trait. Parental
      phenotypes indicated that the majority of the cold-tolerant, dark-germination
      characteristics are related to light responses. Validation of the three major
      loci using heterogeneous inbred families confirmed the feasibility of fine
      mapping and cloning the genes at the quantitative trait loci responsible for cold
      tolerant, dark germination.

PMID- 20031922
TI  - A novel two domain-fusion protein in cyanobacteria with similarity to the
      CAB/ELIP/HLIP superfamily: evolutionary implications and regulation.
AB  - Vascular plants contain abundant, light-harvesting complexes in the thylakoid
      membrane that are non-covalently associated with chlorophylls and carotenoids.
      These light-harvesting chlorophyll a/b binding (LHC) proteins are members of an
      extended CAB/ELIP/HLIP superfamily of distantly related polypeptides, which have
      between one and four transmembrane helices (TMH). This superfamily includes the
      single TMH, high-light-inducible proteins (Hlips), found in cyanobacteria that
      are induced by various stress conditions, including high light, and are
      considered ancestral to the LHC proteins. The roles of, and evolutionary
      relationships between, these superfamily members are of particular interest,
      since they function in both light harvesting and photoprotection and may have
      evolved through tandem gene duplication and fusion events. We have investigated
      the Hlips (hli gene family) in the thermophilic unicellular cyanobacterium
      Synechococcus OS-B'. The five hli genes present on the genome of Synechococcus OS
      B' are relatively similar, but transcript analyses indicate that there are
      different patterns of transcript accumulation when the cells are exposed to
      various growth conditions, suggesting that different Hlips may have specific
      functions. Hlip5 has an additional TMH at the N-terminus as a result of a novel
      fusion event. This additional TMH is very similar to a conserved hypothetical,
      single membrane-spanning polypeptide present in most cyanobacteria. The
      evolutionary significance of these results is discussed.

PMID- 20031923
TI  - Blue-light-independent activity of Arabidopsis cryptochromes in the regulation of
      steady-state levels of protein and mRNA expression.
AB  - Cryptochromes are blue-light receptors that mediate blue-light inhibition of
      hypocotyl elongation and blue-light stimulation of floral initiation in
      Arabidopsis. In addition to their blue-light-dependent functions, cryptochromes
      are also involved in blue-light-independent regulation of the circadian clock,
      cotyledon unfolding, and hypocotyl inhibition. However, the molecular mechanism
      associated with the blue-light-independent function of cryptochromes remains
      unclear. We reported here a comparative proteomics study of the light regulation
      of protein expression. We showed that, as expected, the protein expression of
      many metabolic enzymes changed in response to both blue light and red light.
      Surprisingly, some light-regulated protein expression changes are impaired in the
      cry1cry2 mutant in both blue light and red light. This result suggests that, in
      addition to mediating blue-light-dependent regulation of protein expression,
      cryptochromes are also involved in the blue-light-independent regulation of gene
      expression. Consistent with this hypothesis, the cry1cry2 mutant exhibited
      reduced changes of mRNA expression in response to not only blue light, but also
      red light, although the cryptochrome effects on the red-light-dependent gene
      expression changes are generally less pronounced. These results support a
      hypothesis that, in addition to their blue-light-specific functions,
      cryptochromes also play roles in the control of gene expression mediated by the
      red/far-red-light receptor phytochromes.

PMID- 20031924
TI  - In vivo phosphorylation site mapping and functional characterization of
      Arabidopsis phototropin 1.
AB  - Phototropins (phot1 and phot2) are blue-light receptor kinases controlling a
      range of responses that optimize the photosynthetic efficiency of plants. Light
      sensing is mediated by two flavin-binding motifs, known as LOV1 and LOV2, located
      within the N-terminal region of the protein. Photoexcitation via LOV2 leads to
      activation of the C-terminal kinase domain and consequently receptor
      autophosphorylation. However, knowledge of the in-vivo phosphorylation sites for
      Arabidopsis phototropins is lacking and has impeded progress in elucidating the
      functional significance of receptor phosphorylation. We have purified phot1 from
      Arabidopsis and identified the in-vivo sites of receptor phosphorylation by
      liquid chromatography tandem mass spectrometry. Arabidopsis-derived phot1 binds
      flavin mononucleotide as chromophore and is phosphorylated at four major sites
      located upstream of LOV2 (Ser(58), Ser(85), Ser(350), and Ser(410)), three of
      which are induced by blue light. Nevertheless, structure-function analysis
      indicates that the biological activity of phot1 can be attributed to a modular
      unit comprising the LOV2-kinase region of the protein. Thus, peptide regions
      upstream of LOV2, including the sites of receptor phosphorylation identified
      here, do not appear to be important for receptor signaling. By contrast, these
      regions may be necessary for maximizing stomatal performance and possibly light
      induced relocalization of phot1.

PMID- 20031925
TI  - Validation of the Falls Efficacy Scale-International in fall-prone older persons.

PMID- 20031927
TI  - Demographic histories of four spruce (Picea) species of the Qinghai-Tibetan
      Plateau and neighboring areas inferred from multiple nuclear loci.
AB  - Nucleotide variation at 12-16 nuclear loci was studied in three spruce species
      from the Qinghai-Tibetan Plateau (QTP), Picea likiangensis, P. wilsonii, and P.
      purpurea, and one species from the Tian Shan mountain range, P. schrenkiana.
      Silent nucleotide diversity was limited in P. schrenkiana and high in the three
      species from the QTP, with values higher than in boreal spruce species, despite
      their much more restricted distributions compared with that of the boreal
      species. In contrast to European boreal species that have experienced severe
      bottlenecks in the past, coalescent-based analysis suggests that DNA polymorphism
      in the species from the QTP and adjacent areas is compatible with the standard
      neutral model (P. likiangensis, P. wilsonii, and P. schrenkiana) or with
      population growth (P. purpurea). In order to test if P. purpurea is a diploid
      hybrid of P. likiangensis and P. wilsonii, we used a combination of approaches,
      including model-based inference of population structure, isolation-with-migration
      models, and recent theoretical results on the effect of introgression on the
      geographic distribution of diversity. In contrast to the three other species,
      each of which was predominantly assigned to a single cluster in the Structure
      analysis, P. purpurea individuals were scattered over the three main clusters and
      not, as we had expected, confined to the P. likiangensis and P. wilsonii
      clusters. Furthermore, the contribution of P. schrenkiana was by far the largest
      one. In agreement with this, the divergence between P. purpurea and P.
      schrenkiana was lower than the divergence of either P. likiangensis or P.
      wilsonii from P. schrenkiana. These results, together with previous ones showing
      that P. purpurea and P. wilsonii share the same haplotypes at both chloroplast
      and mitochondrial markers, suggest that P. purpurea has a complex origin,
      possibly involving additional species.

PMID- 20031928
TI  - Variation in IGHMBP2 is not associated with IgA nephropathy in independent
      studies of UK Caucasian and Chinese Han patients.
AB  - BACKGROUND: IgA nephropathy is a major cause of end-stage renal disease
      worldwide. Its aetiology is poorly understood but there is good evidence for a
      major genetic component, although to date, no gene has been conclusively
      identified. We describe a new UK multicentre DNA collection assembled to
      investigate this. A Japanese genome-wide analysis recently reported that common
      genetic variation in immunoglobulin mu-binding protein 2 (IGHMBP2) was associated
      with IgA nephropathy. We sought to replicate this using the new UK collection,
      and through an independent parallel analysis of a Han Chinese population.
      METHODS: In the UK collection, haplotype-tagging (tag) single-nucleotide
      polymorphisms (SNPs) and haplotypes were analysed in a case-control study (349
      cases, 605 controls) and family-based analysis (162 complete and 23 partially
      complete family trios), which was performed using the transmission disequilibrium
      test. In parallel, 663 cases of IgA nephropathy and 663 controls from a Chinese
      population were analysed: coding and flanking regions of the gene were re
      sequenced in a subset, and SNP and haplotype association analysis was performed
      in the whole collection using the identified tagSNPs and all the coding and
      exonic flanking SNPs. RESULTS: Case-control studies in UK and Chinese
      populations, and family-based tests in the UK population provided no evidence for
      association between variation in IGHMBP2 and IgA nephropathy. The A allele of SNP
      G34448A was not present in the UK collection. It was present but not associated
      with the disease in the Chinese population. CONCLUSION: Variation in IGHMBP2 does
      not confer significant susceptibility to IgA nephropathy in UK Caucasian or
      Chinese Han populations.

PMID- 20031926
TI  - Immunoproteomic identification of human T cell antigens of Mycobacterium
      tuberculosis that differentiate healthy contacts from tuberculosis patients.
AB  - Identification of Mycobacterium tuberculosis antigens inducing cellular immune
      responses is required to improve the diagnosis of and vaccine development against
      tuberculosis. To identify the antigens of M. tuberculosis that differentiated
      between tuberculosis (TB) patients and healthy contacts based on T cell
      reactivity, the culture filtrate of in vitro grown M. tuberculosis was
      fractionated by two-dimensional liquid phase electrophoresis and tested for the
      ability to stimulate T cells in a whole blood assay. This approach separated the
      culture filtrate into 350 fractions with sufficient protein quantity (at least
      200 microg of protein) for mass spectrometry and immunological analyses. High
      levels of interferon-gamma (IFN-gamma) secretion were induced by 105 fractions in
      healthy contacts compared with TB patients (p < 0.05). Most interesting was the
      identification of 10 fractions that specifically induced strong IFN-gamma
      production in the healthy contact population but not in TB patients. Other
      immunological measurements showed 42 fractions that induced significant
      lymphocyte proliferative responses in the healthy contact group compared with the
      TB patients. The tumor necrosis factor-alpha response for most of the fractions
      did not significantly differ in the tested groups, and the interleukin-4 response
      was below the detectable range for all fractions and both study groups. Proteomic
      characterization of the 105 fractions that induced a significant IFN-gamma
      response in the healthy contacts compared with the TB patients led to the
      identification of 59 proteins of which 24 represented potentially novel T cell
      antigens. Likewise, the protein identification in the 10 healthy "contact
      specific fractions" revealed 16 proteins that are key candidates as vaccine or
      diagnostic targets.

PMID- 20031929
TI  - Dosing of daptomycin in intensive care unit patients with acute kidney injury
      undergoing extended dialysis--a pharmacokinetic study.
AB  - BACKGROUND: Daptomycin is a new intravenous cyclic lipopeptide antibiotic,
      licensed for the treatment of complicated skin and soft tissue infections caused
      by Gram-positive organisms including both susceptible and resistant strains of
      Staphylococcus aureus and for the treatment of various infections due to
      susceptible organisms, including serious and life-threatening Gram-positive
      infections, vancomycin-resistant enterococcal infections and right-sided
      endocarditis with associated bacteremia. Currently, no dosing recommendations
      exist for this drug for patients with acute kidney injury (AKI) undergoing renal
      replacement therapy. The aim of this study was to evaluate pharmacokinetics of
      daptomycin in critically ill patients with AKI undergoing extended dialysis (ED),
      a frequently used mean of renal replacement therapies in intensive care units
      (ICUs) around the world. Patients and methods. A prospective, single-dose
      pharmacokinetic study was performed in the medical and surgical ICUs of a
      tertiary care center. The aim was to investigate critically ill patients with
      anuric AKI being treated with ED and receiving daptomycin (n = 10). Daptomycin (6
      mg/kg) was administered 8 h before ED was started. RESULTS: Key pharmacokinetic
      parameters like half-life in critically ill patients treated with ED were
      comparable to healthy controls. The dialyser clearance for daptomycin was 63 +/-
      9 ml/min. Based on the amount of the drug recovered from the collected spent
      dialysate, the mean fraction of the drug removed by one dialysis treatment was
      23.3%. CONCLUSION: Our data suggest that patients treated with ED using a high
      flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; ED
      time, 480 min) and employing current dosing regimen, 6 mg/kg daptomycin every 48
      h, run the risk of becoming significantly under dosed if one adheres to a twice
      daily dosing schedule that is recommended for patients on maintenance
      haemodialysis. Our data suggest that a daily dose of 6 mg/kg daptomycin is
      necessary in this special patient population to avoid under dosing, which may
      have detrimental effects in critically ill patients suffering from life
      threatening infections.

PMID- 20031930
TI  - Effects of mycophenolate mofetil on acute ischaemia-reperfusion injury in rats
      and its consequences in the long term.
AB  - BACKGROUND: Renal ischaemia-reperfusion injury (IRI) acutely decreases glomerular
      filtration rate (GFR) and impairs kidney function in the long term. Pre-treatment
      with chaetomellic acid (KM), an inhibitor of membrane-bound Ha-Ras, has
      demonstrated beneficial effects on acute renal ischaemia. METHODS: We tested
      whether mycophenolate mofetil (MMF, 20 mg/day for 4 days before IRI), an
      immunosuppressor with anti-inflammatory properties, improved renal outcome in
      uninephrectomized rats after IRI (45 min of renal ischaemia), alone or in
      combination with KM. RESULTS: One day after ischaemia, GFR was markedly depressed
      in untreated rats (-75% vs. normal rats, P < 0.001), and pre-treatment with MMF
      did not modify this fall (-75%, P < 0.001 vs. normal). KM (0.23 microg/kg before
      IRI) greatly prevented GFR loss (-39% vs. normal, P < 0.05), but its action was
      not further improved by the combined administration with MMF (GFR, -45% vs.
      normal, P < 0.05). MMF significantly reduced ICAM-1 expression and monocyte
      recruitment (P < 0.05 vs. untreated rats); nevertheless, renal histology of MMF
      rats was similar to that of untreated rats. Additional rats were examined 6
      months after IRI: untreated rats with IRI showed reduced renal function (-42% vs.
      normal, P < 0.01) and proteinuria (P < 0.001 vs. normal); rats pre-treated with
      MMF showed a similar pattern, whereas rats treated with KM before IRI presented a
      better GFR (-20% vs. normal, not significant) and near-normal values of
      proteinuria. The combination of KM + MMF gained the same results. CONCLUSIONS:
      Pre-treatment with MMF before IRI does not confer functional or morphological
      protection to the kidney, despite the reduced expression of some inflammatory
      markers. The combination of MMF + KM does not offer additional advantages to
      solitary KM treatment.

PMID- 20031931
TI  - Influence of haemodialysis on variability of pulse wave velocity in chronic
      haemodialysis patients.
AB  - BACKGROUND: The major determinants of pulse wave velocity (PWV) in haemodialysis
      (HD) patients are not fully known. We studied chronic HD patients to assess the
      effect of cyclic variations in both hydration status and blood pressure on PWV.
      METHODS: Twenty patients were examined along three consecutive HD sessions and
      interdialysis periods during a week-long period. Twenty healthy subjects and 20
      chronic kidney disease (CKD) patients (stage 5) were evaluated as controls.
      RESULTS: In contrast to controls, HD patients showed cyclic changes in PWV.
      Specifically, PWV values in HD patients were significantly higher prior to the
      first HD session of the week compared with values measured prior to the other two
      HD sessions during the week. In addition, PWV showed significant reductions
      during each dialysis session (15.6 +/- 5.2 to 9.3 +/- 2.3, 13.4 +/- 4.0 to 8.7 +/
      2.4, and 12.4 +/- 2.6 to 9.2 +/- 2.2 m/sec, before and after the first, second
      and third weekly dialysis sessions, respectively). Nevertheless, the weighted
      weekly values of PWV in HD patients (10.8 +/- 5.7 m/sec) were similar to those in
      CKD patients (9.9 +/- 4.2 m/sec). The HD ultrafiltration rate (UF) was
      significantly correlated with intradialysis PWV changes (r = 0.465; P < 0.001)
      and with after dialysis PWV values (r = -0.654; P < 0.0001). Blood pressure
      changes during dialysis were weakly correlated with post-dialysis PWV (r = 
      0.267; P < 0.05), but not with PWV changes during dialysis. CONCLUSIONS: In
      chronic HD patients, single PWV values varied widely during 1 week of HD
      sessions, whereas the weighted level showed only a slight increase. The major
      determinant of changes in PWV during HD appears to be the alterations in
      hydration status; the most representative time point for PWV measurements during
      HD corresponds to the interdialysis days.

PMID- 20031932
TI  - Blood lead levels association with 18-month all-cause mortality in patients with
      chronic peritoneal dialysis.
AB  - BACKGROUND: The clinical significance of blood lead levels (BLLs) in chronic
      peritoneal dialysis (CPD) patients was undetermined prior to this study. METHODS:
      A total of 315 patients on CPD were included in this 18-month prospective study.
      BLLs measured at baseline were categorized according to a BLL tertile of high
      (>8.66 microg/dL), middle (5.62-8.66 microg/dL) and low (<5.62 microg/dL) for
      cross-sectional analyses. Mortality and cause of death were recorded for
      longitudinal analyses. RESULTS: At baseline, patients with high BLLs had a trend
      of higher parathyroid hormone and lower residual renal function than patients in
      other groups. Stepwise multiple regression analysis found that parathyroid
      hormone positively correlated and residual renal function negatively correlated
      with logarithmic-transformed BLLs in CPD patients after other confounders were
      adjusted. At the end of follow-up, 37 (11.7%) patients had died. Kaplan-Meier
      analysis showed that patients with high BLLs had greater mortality than those
      with middle and low BLLs (P = 0.008). Cox multivariate analysis showed that,
      using the low BLL group as the reference, basal high BLLs (hazard ratio [HR] =
      3.745, 95% confidence interval [95% CI] = 1.218-11.494, P = 0.001) and middle
      BLLs (HR = 1.867, 95% CI = 1.618-2.567, P = 0.001) were associated with increased
      HR for all-cause mortality for CPD patients. There is a significant trend (P <
      0.001) of HR for mortality trend tests among the three study groups. CONCLUSIONS:
      BLLs are associated with residual renal function and hyperparathyroidism and are
      related to increased HR for all-cause 18-month mortality in CPD patients.

PMID- 20031933
TI  - Giant mesenteric cyst of mesothelial origin in a haemodialysis patient with
      previous peritoneal dialysis therapy.
AB  - A 55-year-old female haemodialysis patient presented progressive abdominal liquid
      formation after having been excluded from peritoneal dialysis therapy because of
      recurrent peritonitis. Ultrasound was suspicious for ascites secondary to
      sclerosing peritonitis. Computed tomography revealed a thin-walled mesenteric
      cyst extending from the epigastric to the pelvic region. The cyst was excised
      incompletely as extensive adhesions were present. Histology was consistent with a
      mesothelial cyst of inflammatory origin. Three months after surgery, ultrasound
      detected a local recurrence at the descending colon. This case emphasizes the
      relation between mesenteric cyst, persistent inflammatory status and preceding
      peritoneal dialysis complicated by peritonitis.

PMID- 20031934
TI  - The evidence for the use of oral mucolytic agents in chronic obstructive
      pulmonary disease (COPD).
AB  - INTRODUCTION: Oral mucolytics are now recommended in some treatment guidelines
      for the management of chronic obstructive pulmonary disease (COPD). This article
      reviews the evidence for their use and their possible benefits. SOURCES OF DATA:
      The review is based upon peer reviewed publications relating to the use of
      mucolytics in COPD cited in PubMed. AREAS OF AGREEMENT: Much of the published
      evidence is of somewhat poor quality and many studies include patients with both
      chronic bronchitis and COPD. Mucolytics reduce exacerbations by up to 0.8
      exacerbations per year, but have little additional benefit in those on standard
      maximum therapy. AREAS OF CONTROVERSY: Data that mucolytics improve symptoms,
      alter mucus or impact health-related quality of life in COPD patients receiving
      other standard therapy are unconvincing. In those on little or no other
      treatment, they may reduce exacerbation rate. GROWING POINTS: The use of
      mucolytics to treat acute exacerbations is promising. AREAS TIMELY FOR DEVELOPING
      RESEARCH: Head-to-head trials of mucolytics versus long-acting bronchodilators
      and/or inhaled corticosteroids are lacking. Even in patients with severe COPD who
      remain symptomatic despite maximal inhaled therapy the role of mucolytics remains
      unproven.

PMID- 20031935
TI  - Gender differences in dual task gait performance in older adults.
AB  - Although attention-dividing dual tasks hinder gait performance in older persons,
      gender differences in gait have not been examined. The purpose of this study was
      to examine whether gait performance differs between older men and women during
      dual task walking. A total of 44 healthy adults (20 men and 24 women) aged 65
      years or older participated in the study. Participants walked under normal and
      dual task (backward spelling) conditions at self-selected speeds. Mean gait speed
      and stride-to-stride variability in gait speed were quantified with GAITRite(
      (r)) instrumentation. Whereas gait speed decreased and variability in gait speed
      increased in both groups during dual task walking, men walked with greater
      variability during dual task walking than did women. The magnitude of the
      increase in variability in gait speed observed in men indicates that stride-to
      stride variability in gait speed during dual task walking requires more
      investigation as a potential risk factor for falls in older men.

PMID- 20031936
TI  - Components of body image in gay men with HIV/AIDS.
AB  - The current study examined group differences in various components of body image
      within a group of gay men. Three groups of gay men were compared: AIDS diagnosed,
      HIV positive (without an AIDS diagnosis), and HIV negative. Participants were 254
      men who responded to an online survey. Results revealed significant group
      differences on the components of illness orientation and fitness/health
      evaluation. These results indicated that participants in the AIDS and HIV
      positive groups reported more awareness of and vulnerability to illness compared
      with the HIV negative group. Furthermore, men in the AIDS group reported being
      less fit and in poorer health than HIV positive and HIV negative men.
      Surprisingly, there were no significant differences between groups on appearance
      evaluation, suggesting that previous reports of high levels of body
      dissatisfaction among men living with HIV/AIDS may be because of disproportionate
      rates of gay (or MSM) men affected by the disease.

PMID- 20031937
TI  - Incidence of testicular cancer in the United States, 1999-2004.
AB  - Testicular cancer is rare but primarily affects young men. To characterize the
      current incidence of testicular cancer in the United States, U.S. Cancer
      Statistics data from 1999 through 2004 were examined. Age-adjusted (2000 U.S.
      standard) incidence rates were calculated for seminoma and nonseminoma testicular
      germ cell tumors (TGCTs). Hispanic men had the largest increase in incidence
      rates for nonseminomas, followed by non-Hispanic White men (annual percentage
      change of 3.2% and 1.9%, respectively, p < .05). Nonseminomas peaked at a younger
      age for Hispanic, American Indian/Alaska Native (AIAN), and Asian/Pacific
      Islander (API) men. Whereas 9.6% of TGCTs were diagnosed at a distant stage in
      non-Hispanic White men, more Hispanic (16.1%), Black (13.8%), AIAN (16.8%), and
      API (14.9%) men with TGCTs were diagnosed with distant stage. Monitoring
      incidence rates for rare cancers by race/ethnicity has improved with national
      population-based cancer registry coverage. Disparities in diagnosis stage have
      implications for effective treatment of TGCTs.

PMID- 20031938
TI  - The burden of care of gay male carers caring for men living with HIV/AIDS.
AB  - OBJECTIVE: The notion of caregiver 'burden' has been used as a term that refers
      to the financial, physical and emotional effects of caring. This Australian 2002
      research investigated the caregiver burden of HIV/AIDS on the gay male carers of
      gay men with the disease. METHODS: This study was a phenomenological inquiry and
      employed van Manen's approach to content analysis. Data saturation occurred at
      twelve participants. RESULTS: The findings produced carer themes relating to
      coping with the burden of care of a person living with HIV/AIDS (PLWHA) in the
      context of living day-to-day with HIV/AIDS, coping with the last phase of AIDS
      toward death, saying goodbye and remembrance. CONCLUSION: Allocating resources to
      gay male carers such as; education, respite care, family therapy and cognitive
      behavioral therapy (CBT) to address grief and stigma issues, has implications for
      how health services might reduce the burden of care for these carers.

PMID- 20031939
TI  - Single port access transumbilical laparoscopic Roux-en-Y gastric bypass using the
      SILS Port: first reported case.
AB  - The emergence of natural orifice translumenal endoscopic surgery (NOTES) has
      brought significantly more attention to the single-incision transumbilical
      laparoscopic approach (SILS) for minimally invasive surgery. SILS combines the
      cosmetic advantage of NOTES with the technical familiarity of the conventional
      multiport laparoscopic approach. Additionally, SILS does not involve penetration
      of an organ, nor does it involve the steep learning curve and costly instruments
      associated with NOTES. Given these advantages, the authors believe that the
      single-incision transumbilical approach highlights the future direction of
      minimally invasive surgery. However, because of the associated technical
      challenges, the single-incision approach has not quite yet achieved the crossover
      to advanced surgical procedures that conventional multiport laparoscopy achieved
      in its early years. In this report, the authors present what is, to the best of
      their knowledge, the first reported case of a single-port access laparoscopic
      Roux-en-Y gastric bypass using the SILS Port placed through a single
      intraumbilical skin incision.

PMID- 20031940
TI  - Single-access gastrostomy (SAG) dispenses endoscopy or laparoscopy: a simple
      method under local anesthesia.
AB  - OBJECTIVE: Gastrostomy for feeding or desobstructive purposes is often performed
      transendoscopically. However, as endoscopy specialists and instruments are not
      widely available in community hospitals in Brazil, an alternative method was
      developed at the authors' institution. Surgical single-access gastrostomy (SAG),
      performed under local anesthesia and requiring no endoscopic guidance is
      described. METHODS: The authors used the SAG technique on 19 patients eligible
      for gastrostomy, and the data were prospectively documented. After local
      anesthesia and a 1-cm incision, the gastric wall was localized under direct
      vision. Purse string sutures were placed to work as a fixed valve to rectus
      sheath. RESULTS: SAG was feasible in all patients. Minor complications occurred
      in 3 patients. The mean operative time was 44.2 minutes, and the mean institution
      of gastrostomy feeding was 27.8 hours. CONCLUSION: SAG may dispense with the use
      of endoscopy and laparoscopy, providing a feasible, reproducible, and effective
      feeding gastrostomy in developing countries where alternative methods are not
      available.

PMID- 20031941
TI  - Timing and dose of tissue plasminogen activator to prevent abscess formation
      after surgical treatment of secondary peritonitis in the rat.
AB  - Early administration of fibrinolytics after surgical treatment of peritonitis in
      the rat reduces abscess formation. The current study investigates the effect of
      various treatment protocols using intraperitoneal recombinant tissue plasminogen
      activator (rtPA). Peritonitis was induced in rats and surgical debridement was
      performed after 1 hour. Animals were treated with rtPA at different time points.
      Abdominal fluid samples were taken at 24, 72, and 120 hours for cytokine
      measurements and cell counts. After 5 days the abdomen was inspected for
      abscesses. Early administration of rtPA significantly reduced the number of rats
      with abscesses and the abscess load per rat. Delayed treatment significantly
      reduced abscess load but not the incidence of abscesses. No meaningful
      differences in the local inflammatory response were found. rtPA was most
      effective when applied early and continued for 72 hours, although mortality
      increased after prolonged treatment. rtPA consistently reduces intra-abdominal
      abscess formation, and a clinical study seems warranted.

PMID- 20031942
TI  - Laparoscopic partial nephrectomy using FloSeal for hemostasis: technique and
      experiences in 102 patients.
AB  - OBJECTIVES: The authors report their techniques, perioperative data, and
      oncological outcome for laparoscopic partial nephrectomy in a single-center
      experience with 3 different surgeons. PATIENTS AND METHODS: A total of 102
      consecutive patients underwent laparoscopic transperitoneal partial nephrectomy
      for exophytic tumors using FloSeal for hemostasis. Mean age was 58 years (range =
      26-79 years), and median tumor size was 2.6 cm (range = 0.5-8.5 cm). In 84 cases,
      the renal artery was clamped using endoscopic bulldog clamps, and tumor resection
      was performed using scissors or the harmonic scalpel. Hemostasis was achieved by
      application of FloSeal; lesions of the collecting system were closed with Lahodny
      sutures in 33 cases (31%). Frozen sections were obtained for margin status.
      RESULTS: All 102 procedures were successful with no intraoperative complications.
      Mean surgical time was 201 minutes (range = 60-355 minutes); clamping time was
      25.8 minutes (range = 6-75 minutes) in 64 cases. Margins were negative in 92
      cases; in 8 cases secondary resection was necessary to achieve negative margin
      status, and in 2 cases radical nephrectomy was performed. Histological findings
      were clear-cell carcinoma in 51 (50.0%), papillary carcinoma in 26 (25.5%), and
      others in 25 (24.5%) cases. At a mean follow-up of 32 months (12-62 months), no
      recurrence was observed. CONCLUSIONS: Laparoscopic partial nephrectomy with the
      use of FloSeal is a feasible and safe method for treatment of small renal masses.
      The technique is reproducible by surgeons who are used to complex laparoscopic
      procedures. Patient outcome during follow-up was comparable with data published
      for open standard procedures.

PMID- 20031943
TI  - Major complications associated with xenograft biologic mesh implantation in
      abdominal wall reconstruction.
AB  - BACKGROUND: There is limited research for xenograft biologic mesh performance in
      the setting of infection despite widespread use and significant associated costs.
      DESIGN: The authors retrospectively reviewed an FDA database for reported
      xenograft adverse events (AEs). All meshes were used in the setting of abdominal
      wall reconstruction from 1997 to 2008. RESULTS: The authors identified 150 AEs.
      Permacol and Collamend comprised 75% (n = 112) of reported cases. Main AEs
      included acute mechanical failure (42%; n = 63), mesh disintegration (32%; n =
      48), and poor mesh integration (13%; n = 20); 80% of cases were described as
      infected, and nearly 90% of AEs required reoperation. CONCLUSIONS: Major
      complications are reported to the FDA for xenograft biologic meshes. Cross-linked
      meshes had the most AE reports to the FDA. The intrinsic properties of meshes and
      how they relate to infection-related outcomes are poorly understood. The findings
      from this FDA database review point toward a need to carefully evaluate these
      products.

PMID- 20031944
TI  - Cholecystectomy by single trocar access (SITRACC): the first multicenter study.
AB  - BACKGROUND: The advent of endoscopic surgery has radically changed surgery
      worldwide.The concept of minimally invasive procedures has spread quickly,
      allowing less pain and more rapid recovery for patients. The authors have
      developed a device for a new surgical approach, the so-called single trocar
      access (SITRACC). This study report the first multicenter study of
      cholecystectomies performed with SITRACC. METHODS: Between December 2008 and June
      2009, 81 single trocar cholecystectomies were performed in 9 Brazilian surgery
      centers. RESULTS: The average operative time was 68 minutes. In all, 10 surgeries
      required 1 additional trocar because of technical problems, and 3
      cholecystectomies were converted to standard video laparoscopies. CONCLUSION: A
      cholecystectomy using the SITRACC method is feasible and safe.

PMID- 20031945
TI  - Choosing surgical lighting in the LED era.
AB  - BACKGROUND: The aim of this study is to evaluate the illumination characteristics
      of LED lights objectively to ease the selection of surgical lighting. METHODS:
      The illuminance distributions of 5 main and 4 auxiliary lights were measured in 8
      clinically relevant scenarios. For each light and scenario, the maximum
      illuminance E(c) (klux) and the size of the light field d(10) (mm) were computed.
      RESULTS: The results showed: that large variations for both E(c) (25-160 klux)
      and d(10) (109-300 mm) existed; that using auxiliary lights reduced both E(c) and
      d(10) by up to 80% and 30%; that with segmented lights, uneven light
      distributions occurred; and that with colored LED lights shadow edges on the
      surgical field became colored. CONCLUSIONS: Objective illuminance measurements
      show a wide variation between lights and a superiority of main over auxiliary
      lights. Uneven light distributions and colored shadows indicate that LED lights
      still need to converge to an optimal design.

PMID- 20031946
TI  - Increased utilization of flexible endoscopic methods during colorectal resection
      over a 3-year period.
AB  - INTRODUCTION: Intraoperative endoscopy (IE) is performed during some colorectal
      resections (CRR) mainly to inspect circular stapled anastomoses (CSA) and to
      locate small neoplasms. This study's purpose was to determine how often rigid and
      flexible lower endoscopic methods were used during CRR by one colorectal surgeon
      over three 1-year periods. METHODS: Data concerning the indication for surgery
      and IE, type of resection, and the use of rigid and flexible methods were
      obtained from a prospective database and from hospital charts during Period 1
      (P1), 1/1/05 to 12/31/05; P2, 7/1/06 to 6/31/07; and P3, 7/01/07 to 6/30/08. The
      endoscopic CO2 insufflation device was introduced during P2. The utilization
      rates (UR) for rigid and flexible methods and the overall UR in each time period
      were compared. The chi(2) and Fisher exact test were used for analysis. RESULTS:
      No significant differences were found in overall endoscopy UR between periods (94
      109/per period.) A significantly higher flexible UR was noted during P3 (43.1% of
      all CRR) than during P1 (18.6%, P < .001) or P2 (28.7%, P < .03). There was a
      concomitant significant drop in the rigid UR during Period 3 (1.8% of all CRR)
      when compared with P1 (24.5%, P < .001) or P2 (27.7%, P < .001). CONCLUSION: The
      overall UR did not significantly vary; however, during P3 the flexible UR
      increased whereas the rigid UR decreased (vs P1, P2; P < .05). The addition of
      extra endoscopes and an endoscopic CO2 insufflation device to the operating room
      coincided with increased flexible UR.

PMID- 20031947
TI  - Surgical Abdominal Wall (SAW): a novel simulator for training in ventral hernia
      repair.
AB  - Laparoscopic ventral hernia repair (LVHR) is a relatively common procedure that
      requires advanced minimally invasive surgical skills to perform. The role for
      simulation is increasingly supported as an effective way to teach surgical skills
      and accelerate the learning curve. This article describes The University of
      Maryland's Surgical Abdominal Wall, an inexpensive procedure-specific physical
      simulator for LVHR, and summarizes the authors' early experiences using this
      model in a curriculum for surgery residents.

PMID- 20031948
TI  - Single-port access: a feasible alternative to conventional laparoscopic
      splenectomy.
AB  - HYPOTHESIS: The laparoscopic approach has become the gold standard for
      splenectomy despite the fact that the spleen is a solid organ located deep in the
      splenic fossa. There is currently a trend to reduce the invasiveness of minimally
      invasive procedures. Transabdominal or transumbilical single-incision
      laparoscopic (SILS) approaches are an alternative to natural orifice transluminal
      endoscopic surgery techniques, but no reports of their use have yet been
      published in relation to the spleen. AIM: To describe the SILS technique for
      splenectomy in 2 patients. MATERIAL AND METHODS: Two patients were approached by
      SILS, a 26-year-old male diagnosed of autoimmune thrombocytopenia and a 45-year
      old male with recurrent Hodgkin disease. In both cases 3 trocars (1 of 12 mm and
      2 of 5 mm) were inserted through the umbilicus in one and in a left subcostal in
      the other, and a curved transanal endoscopic microsurgery instrument, a flexible
      tip 10-mm scope, and the UltraCision were introduced. Visualization of the spleen
      and standard dissection of attachments were feasible, and splenectomy was
      completed using transumbilicus stapling of the splenic hilum. The spleen was
      extracted through the umbilical incision, intact in one case and after
      morcellation in the other. RESULTS: The postoperative course was uneventful. Both
      patients had minimal postoperative pain and scarring and were discharged on the
      second postoperative day. CONCLUSIONS: SILS access can be safely used for
      operative visualization, hilum transection, and spleen removal with conventional
      instrumentation, reducing parietal wall trauma to a minimum. The clinical,
      esthetic, and functional advantages require further analysis.

PMID- 20031949
TI  - A meta-analysis of erythropoiesis-stimulating agents in anaemic patients with
      chronic heart failure.
AB  - AIMS: Anaemia is a frequent comorbidity in patients with chronic heart failure
      (CHF) and is associated with worse outcomes. It is logical to consider whether
      correcting anaemia is a novel therapeutic target in such patients. We performed a
      meta-analysis to explore whether treatment of anaemia with erythropoietin
      stimulating agents (ESA) can improve symptoms and progression in patients with
      CHF. METHODS AND RESULTS: Studies were identified in English-language articles by
      searching PUBMED (inception to May 2009). A standardized protocol with predefined
      criteria was used to extract details on study design, Jadad score, demographic
      data, interventions, and outcomes. The main outcome measures were cardiac
      function, exercise capacity, quality of life, and all-cause mortality. Seven
      randomized controlled trials involving 678 patients were identified and included
      in the analysis. Cardiac function as well as exercise capacity were improved post
      treatment in the ESA group; however, the overall deaths analysis demonstrated a
      lower trend but no significant protective effect in the ESA treatment group (RR,
      0.71; 95% confidence interval, 0.41-1.24; P = 0.23). CONCLUSION: This meta
      analysis suggests a symptomatic improvement in anaemic patients with CHF
      receiving ESA. However, a non-significant reduction in all-cause mortality in the
      ESA treatment group compared with the control group was observed.

PMID- 20031951
TI  - High-intensity transient signals during laparoscopic surgery in children.
AB  - BACKGROUND: Laparoscopic interventions in children gain increasing popularity.
      Pneumoperitoneum as applied during laparoscopic surgery can induce gas emboli
      formation, but it is unclear whether this is associated with cerebral embolic
      events. To investigate the hypothesis that pneumoperitoneum causes cerebral
      emboli in children, the number and intensity of high-intensity transient signals
      (HITS) detected using transcranial Doppler ultrasonography were assessed before
      and after induction of pneumoperitoneum. METHODS: Twenty children were monitored
      during laparoscopic surgery. General anaesthesia was performed using sevoflurane
      and sufentanil or alfentanil. Pressure-controlled ventilation was adapted to
      maintain end-tidal Pco(2) (Pe'(co(2))) between 4.7 and 6.0 kPa. Baseline
      measurement of HITS rate, cerebral blood flow velocity, and mean arterial
      pressure (MAP) were recorded during steady-state anaesthesia before skin incision
      and during pneumoperitoneum with intra-abdominal pressure of 1.6-2.0 kPa applied
      using CO(2). RESULTS: In 14 children (70%), HITS were detected during baseline
      and pneumoperitoneum. Three additional children (15%) developed HITS during
      pneumoperitoneum only and another three children (15%) presented no HITS during
      the investigation period. MAP and cerebral blood flow velocity increased with
      pneumoperitoneum. CONCLUSIONS: HITS are present in 70% of paediatric surgical
      patients under balanced anaesthesia before surgical interventions.
      Pneumoperitoneum further increased the occurrence of HITS.

PMID- 20031950
TI  - Monitoring of the responsiveness to noxious stimuli during anaesthesia with
      propofol and remifentanil by using RIII reflex threshold and bispectral index.
AB  - BACKGROUND: Movement responses are an important indicator of noxious perception
      in the unconscious state. To allow for a continual monitoring of the
      responsiveness to noxious stimuli during general anaesthesia, surrogate
      parameters are needed. Here we compare the performance of the bispectral index
      (BIS) and the RIII threshold in predicting reactions to noxious stimuli during
      anaesthesia with propofol and remifentanil. METHODS: Twenty male volunteers were
      included. The first 10 subjects received constant concentrations of propofol
      while remifentanil concentrations were increased stepwise. The other 10 subjects
      each received high propofol concentrations combined with different low
      remifentanil concentrations and also low propofol concentrations combined with
      different high remifentanil concentrations. In all subjects, the reactions to an
      80 mA 30 s tetanic stimulus were tested every 5 min. BIS and RIII threshold were
      recorded continually in all subjects. RESULTS: Nineteen subjects completed the
      study. The population prediction probability for reactions to the noxious stimuli
      amounted to 0.86 for the BIS and to 0.84 for the RIII threshold in the first 10
      subjects (P>0.05, PKDMACRO). In the other nine subjects, the prediction
      probabilities amounted to 0.64 for the BIS and to 0.77 for the RIII threshold
      (P<0.05, PKDMACRO). All population prediction probability values differed
      significantly from 0.5 (P<0.01, PKDMACRO). CONCLUSIONS: RIII threshold and BIS
      are both influenced dose-dependently by remifentanil at those concentrations that
      suppress reactions to noxious stimuli. The susceptibility of the parameters to
      remifentanil concentration seems to be of a similar quality. Under different
      ratios of propofol and remifentanil concentrations, the RIII threshold correlates
      with non-responsiveness better than the BIS.

PMID- 20031952
TI  - Differential effects of lumbar and thoracic epidural anaesthesia on the
      haemodynamic response to acute right ventricular pressure overload.
AB  - BACKGROUND: The safety of epidural anaesthesia in patients at risk for right
      ventricular pressure overload remains controversial. We compared the haemodynamic
      effects of vascular and cardiac autonomic nerve block, induced by selective
      lumbar (LEA) and high thoracic epidural anaesthesia (TEA), respectively, in an
      animal model subjected to controlled acute right ventricular pressure overload.
      METHODS: Eighteen pigs were instrumented with epidural catheters at the thoracic
      (T) and lumbar (L) level and received separate injections at T2 (1 ml) and L3 (4
      ml) with saline (s) or bupivacaine 0.5% (b). Three groups of six animals were
      studied: (i) a control group (Ls+Ts), (ii) LEA group (Lb+Ts), and (iii) TEA group
      (Ls+Tb). Haemodynamic measurements including biventricular pressure-volumetry
      were performed. Right ventricular afterload was then increased by inflating a
      pulmonary artery (PA) balloon. Measurements were repeated after 30 min of
      sustained right ventricular afterload increase. RESULTS: LEA decreased systemic
      vascular resistance (SVR) and did not affect ventricular function. TEA had minor
      effects on SVR but decreased left ventricular contractility while baseline right
      ventricular function was not affected. Control and LEA-treated animals responded
      similarly to a PA balloon occlusion with an increase in right ventricular
      contractility and heart rate. Animals pretreated with a TEA did not show this
      positive inotropic response and developed low cardiac output in the presence of
      right ventricular pressure overload. CONCLUSIONS: In contrast to LEA, TEA reduced
      the haemodynamic tolerance to PA balloon occlusion by inhibiting the right
      ventricular positive inotropic response to acute pressure overload.

PMID- 20031953
TI  - Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive
      effect of ketamine.
AB  - BACKGROUND: The aim of this study was to assess the preventative effect of
      ketamine on the exaggerated postoperative pain observed in sufentanil-treated
      mice and its ability to improve the analgesic effectiveness of morphine during
      the postoperative period in an orthopaedic model of pain. METHODS: In this study,
      we assessed the effects of ketamine on sufentanil enhancement of pain behaviour
      induced by fracture and the effects of ketamine on postoperative morphine-induced
      analgesia. Three tests were used to assess pain behaviour: von Frey filament
      application, hot-plate test, and a subjective pain scale. RESULTS: When
      administered 1 day after surgery in mice treated with sufentanil on D0 (before
      surgery), morphine induced an analgesic effect as observed by the nociceptive
      threshold increase in saline- and ketamine-treated mice. Morphine was more
      effective in ketamine-treated (1 and 50 mg kg(-1)) mice. CONCLUSIONS: Our results
      suggest that pre-emptive use of ketamine is useful in orthopaedic surgery in this
      mice model to diminish short- and long-term hyperalgesia, but also to improve
      morphine effectiveness leading to a better mobilization and more rapid
      rehabilitation.

PMID- 20031954
TI  - Lack of exercise decreases survival and increases organ damage after hemorrhagic
      shock in rats.
AB  - Inflammatory response secondary to hemorrhagic shock (HS) frequently precedes
      multiple organ failure and death in trauma patients. Researchers have recognized
      that exercise benefits immune function. However, the effects of exercise on
      HSinduced death and organ damage are unknown. In this study, the authors aimed to
      explore the effects of exercise on survival rate and organ injury after HS. Rats
      were divided into exercise and nonexercise groups. The exercise group received
      running training 30 min/day five times/week for 4 weeks. After 4 weeks,
      researchers withdrew 60% of total blood volume in both groups to mimic HS. Levels
      of blood aspartate transferase (GOT), alanine transferase (GPT), blood urea
      nitrogen (BUN), creatinine (Cr), lactic acid dehydrogenase (LDH), creatine kinase
      myoglobin (CK-MB), blood glucose, and lactate were measured. The survival rate
      and injury scores for the liver, kidney, and lung were examined 48 hr after HS.
      Physical activity was measured in surviving rats from the 3rd to the 7th day
      after HS. Exercise training significantly increased the survival rate (75% for
      the exercise group vs. 50% for the nonexercise group) after HS and decreased
      organ injury. In addition, the exercise group was more active than the
      nonexercise group after HS.

PMID- 20031955
TI  - The role of doxycycline as a matrix metalloproteinase inhibitor for the treatment
      of chronic wounds.
AB  - Many chronic wounds fail to heal with conventional therapy, resulting in
      disability and impaired quality of life. New technologies using recombinant
      growth factors, autologous growth factors, or bioengineered skin-tissue
      substitutes have been shown to be effective, but these treatments are costly. An
      effective, low-cost treatment to improve healing of chronic wounds is needed. The
      molecular environment of chronic wounds, like many other chronic inflammatory
      diseases, contains abnormally high levels of proinflammatory cytokines (tumor
      necrosis factor [TNF]-alpha and interleukin [IL]-1beta]) and matrix
      metalloproteinases (MMPs), which impair normal wound healing. In animal models
      and clinical studies of ulcerative diseases, doxycycline, an inexpensive and Food
      and Drug Administration (FDA)-approved antibiotic, appears to inhibit members of
      the MMP superfamily like MMPs and TNF-alpha-converting enzyme (TACE). This
      article provides an overview of the roles of MMPs and intrinsic tissue inhibitors
      of metalloproteinases (TIMPs) in wound healing and the damaging effects of
      chronically elevated levels of MMPSs in chronic wounds. It also explores the use
      of topical doxycycline, a synthetic MMP inhibitor (MMPI), to enhance healing of
      chronic wounds.

PMID- 20031956
TI  - Effects of exogenous testosterone supplementation in gonadotrophin stimulated
      cycles.
AB  - BACKGROUND: Various experiments suggest that ovarian follicular recruitment and
      growth may be increased by testosterone priming. Our aim was to determine the
      effects of exogenous testosterone supplementation in older women on ovarian
      folliculogenesis and steroidogenesis. METHODS: A prospective randomized double
      blind placebo-controlled crossover study was carried out. Twelve regularly
      menstruating non-obese women aged 38-45 years received a 12-day course of
      transdermal testosterone (2.5 mg per patch) or placebo patch, followed by 7 days
      of gonadotrophin stimulation. After at least a 1 month washout period, subjects
      underwent the same protocol using the opposite treatment. The main outcomes were
      follicular development (ultrasound measures) and hormone levels. RESULTS:
      Following gonadotrophin stimulation, there were no differences in average number
      of follicles over 10 mm diameter in cycles pre-treated with testosterone versus
      placebo [2.10 (95% confidence interval (CI) 1.11, 3.22) versus 2.08 (95% CI 1.03,
      3.14), P = 0.55]. No crossover, period (first or second test) or sequence (order
      of treatment) effects were noted. As expected, total and free testosterone levels
      were increased following testosterone treatment (312.7 +/- 122.4 versus 12.3 +/-
      4.5 ng/dl and 45.5+/- 16.7 versus 1.4 +/- 0.5 ng/dl, respectively, P < 0.001) but
      no differences in free or total testosterone were noted by period. LH, FSH,
      estradiol and antral follicle counts before gonadotrophin stimulation were not
      altered by testosterone pretreatment or by period. CONCLUSIONS: Despite increased
      testosterone levels, a short course of androgens had no significant effect on the
      number of follicles over 10 mm during stimulation with FSH in women of late
      reproductive age.

PMID- 20031957
TI  - What next for preimplantation genetic screening? A polar body approach!
AB  - Screening of human preimplantation embryos for numerical chromosome abnormalities
      has been conducted mostly at the preimplantation stage using fluorescence in situ
      hybridization. However, it is clear that preimplantation genetic screening (PGS)
      as it is currently practiced does not improve live birth rates. Therefore the
      ESHRE PGS Task Force has decided to start a proof of principle study with the aim
      of determining whether biopsy of the first and second polar body followed by
      subsequent analysis of the complete chromosome complement of these polar bodies
      using an array based technique enables a timely identification of the chromosomal
      status of an oocyte. If the principle of this approach can be proven, it is
      obvious that a multicentre randomized controlled trial should then be started to
      determine the clinical value of this technique. In this way the ESHRE PGS Task
      Force hopes to redirect preimplantation screening from the blind alley to the
      main road of assisted reproduction.

PMID- 20031958
TI  - Statins, fibrates, and venous thromboembolism: a meta-analysis.
AB  - AIMS: The aim is to make a systematic review of the literature to assess the
      effect of lipid-lowering drugs on venous thromboembolism (VTE) occurrence.
      METHODS AND RESULTS: MEDLINE and EMBASE databases were searched to identify
      studies that evaluated the effect of lipid-lowering drugs, in particular statins
      and fibrates, on VTE risk until April 2009. A scoring system was used to divide
      studies into two quality categories. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were then calculated and pooled using a fixed and a random
      effects model. Statistical heterogeneity was evaluated through the use of I(2)
      statistics. Three randomized controlled trials (RCTs), three cohort, and eight
      case-control studies were included in our systematic review, for a total of 863
      805 patients. Statins use significantly reduced VTE risk [OR, 0.81; 95% CI, 0.66
      0.99, random-effect model)]. There was a very high heterogeneity among the
      studies (I(2) > 80%). The use of fibrates was associated with a significant
      increase in the risk of VTE (OR, 1.58; 95% CI, 1.23-2.02), without heterogeneity
      (I(2) = 0%). Data on other lipid-lowering drugs were lacking. CONCLUSION: This
      meta-analysis of available literature suggests that statins may lower the risk of
      VTE, whereas fibrates may increase this risk. Due to several methodological
      limitations, this conclusion should be considered with caution, and additional,
      specifically designed RCTs are warranted.

PMID- 20031959
TI  - The gene expression profile of patients with new-onset heart failure reveals
      important gender-specific differences.
AB  - AIMS: We sought to test the hypothesis that inherent biological factors
      contribute to gender differences in disease pathophysiology of new-onset heart
      failure (HF), which can be detected from the transcriptome of a single
      endomyocardial biopsy (EMB). METHODS AND RESULTS: We analysed samples from male
      (n = 29) and female patients (n = 14) with idiopathic dilated cardiomyopathy
      (IDCM) and new-onset HF with U133 Plus 2.0 microarrays (Affymetrix) and
      significance analysis of microarrays (SAM). There were 35 overexpressed and 16
      downregulated transcripts in men vs. women [q < 5%, fold change (FC) > 1.2]. In
      addition to overexpression of Y-chromosome-related transcripts (n = 18), such as
      USP9Y (FC > 13.1), DDX3Y (FC > 11.3), RPS4Y1 (FC > 9.9), and EIF1AY (FC > 11.8)
      in males, there was overexpression of CD24 (FC > 5.6) and KCNK1 (FC > 1.5). In
      females, XIST was highly overexpressed (FC > 28.9), together with X-linked zinc
      finger proteins (FC > 1.9) and autosomal genes GATAD1 (FC > 1.6), SLC2A12 (FC >
      2.9), and PDE6B (FC > 1.5). Analysis of a public data set of end-stage IDCM (n =
      15) resulted in approximately 85% overlap with our findings. CONCLUSION: This is
      the first study that identified gender-specific transcriptomic differences in new
      onset HF. Our findings may offer novel insights into fundamental biological
      differences in the pathophysiology of HF between sexes and provide a platform for
      personalized medicine.

PMID- 20031960
TI  - Structure and activities of adult congenital heart disease programmes in Europe.

PMID- 20031961
TI  - Extraperitoneal approach induces postoperative inguinal hernia compared with
      transperitoneal approach after laparoscopic radical prostatectomy.
AB  - OBJECTIVE: The aim of this study was to determine the incidence and risk factors
      of postoperative inguinal hernia and to investigate whether the difference of
      approach could induce postoperative inguinal hernia after laparoscopic radical
      prostatectomy. METHODS: We reviewed 493 consecutive patients who underwent
      laparoscopic radical prostatectomy from November 2000 to November 2007, and
      evaluated various preoperative parameters, specifically age, prostate-specific
      antigen (ng/ml), body mass index (kg/m(2)), prostate volume (ml), previous major
      abdominal surgery, previous appendectomy, previous inguinal hernia repair and
      laparoscopic approach as risk factors for postoperative inguinal hernia. RESULTS:
      Inguinal hernia occurred in 4 (4.9%) of the 81 patients in the transperitoneal
      approach group, and in 37 (9.0%) of the 412 patients in the extraperitoneal
      approach group. The overall incidence of inguinal hernia was 8.3% (41 of 493
      patients). The median inguinal hernia-free survival time was 35 months and 6
      months in the transperitoneal approach and extraperitoneal approach groups,
      respectively. Inguinal hernia developed within 2 years after surgery in 2 (50%)
      of 4 patients in the transperitoneal approach group, in 34 (91.9%) of 37 patients
      in the extraperitoneal approach group, for a total of 36 (87.8%) of 41 patients
      overall. Multivariate analysis showed that the extraperitoneal approach was a
      significant risk factor (P = 0.043) for inguinal hernia. CONCLUSIONS: Inguinal
      hernia is a frequent complication after laparoscopic radical prostatectomy, and
      the incidence of inguinal hernia is greater with the extraperitoneal approach
      than with the transperitoneal approach.

PMID- 20031962
TI  - Advances in target therapy for lung cancer.
AB  - Recent progress in molecular biology has shown that cancer cells acquire common
      phenotypes such as self-sufficiency of growth signals, resistance to anti
      proliferative and apoptotic signals through the accumulation of genetic and
      epigenetic changes. Recently developed anticancer drugs target these molecular
      mechanisms and good results have been reported for various cancer types. In lung
      cancer, tyrosine kinase inhibitors specific for the epidermal growth factor
      receptor such as gefitinib and erlotinib have changed clinical practice
      dramatically. About half of the Japanese patients with lung cancers harbor an
      activating mutation of the epidermal growth factor receptor gene and they are
      very sensitive to epidermal growth factor receptor tyrosine kinase inhibitors.
      Progression-free survival of such patients is approximately 10 months when
      treated with gefitinib, whereas the survival for those treated with platinum
      doublet therapy is approximately 6 months. Target therapies against echinoderm
      microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein
      or a mutated ERBB2 (v-ERB-B avian erythroblastic leukemia viral oncogene
      homologue 2) present in approximately 5% and approximately 3% of the Japanese
      patients with adenocarcinomas, respectively, are currently under development.
      Addition of an anti-epidermal growth factor receptor antibody, cetuximab, or anti
      vascular endothelial growth factor antibody, bevacizumab, to platinum doublet
      therapy significantly but modestly prolonged the survival in recent clinical
      trials. However, clinical development of small molecule multi-kinase inhibitors
      including those targeting vascular endothelial growth factor receptors, such as
      vandetanib, sunitinib and sorafenib, has not been very successful. Through these
      collaborations among clinicians, basic researchers and pharmaceutical companies,
      it should be possible to individualize lung cancer treatment to turn this fatal
      disease into a chronic disorder and, eventually, to cure it.

PMID- 20031963
TI  - Ancient news: HMGBs are universal sentinels.
AB  - Yanai et al. (2009, Nature 462, 99-103) have shown that high mobility group boxs
      (HMGBs) are universal sensors of viral nucleic acids, and thus of cell infection.
      This appears to be an evolutionary ancient mechanism of virus detection, and
      possibly might be a facet of a more general propensity of HMGBs to act as
      integrators of signals that pertain to peace and stress, life and death.

PMID- 20031964
TI  - Effect of water hardness on cardiovascular mortality: an ecological time series
      approach.
AB  - BACKGROUND: Numerous studies have suggested an inverse relationship between
      drinking water hardness and cardiovascular disease. However, the weight of
      evidence is insufficient for the WHO to implement a health-based guideline for
      water hardness. This study followed WHO recommendations to assess the feasibility
      of using ecological time series data from areas exposed to step changes in water
      hardness to investigate this issue. METHOD: Monthly time series of cardiovascular
      mortality data, subdivided by age and sex, were systematically collected from
      areas reported to have undergone step changes in water hardness, calcium and
      magnesium in England and Wales between 1981 and 2005. Time series methods were
      used to investigate the effect of water hardness changes on mortality. RESULTS:
      No evidence was found of an association between step changes in drinking water
      hardness or drinking water calcium and cardiovascular mortality. The lack of
      areas with large populations and a reasonable change in magnesium levels
      precludes a definitive conclusion about the impact of this cation. We use our
      results on the variability of the series to consider the data requirements (size
      of population, time of water hardness change) for such a study to have sufficient
      power. Only data from areas with large populations (>500,000) are likely to be
      able to detect a change of the size suggested by previous studies (rate ratio of
      1.06). CONCLUSION: Ecological time series studies of populations exposed to
      changes in drinking water hardness may not be able to provide conclusive evidence
      on the links between water hardness and cardiovascular mortality unless very
      large populations are studied. Investigations of individuals may be more
      informative.

PMID- 20031966
TI  - DCDB: drug combination database.
AB  - SUMMARY: Rapid advances in pharmaceutical sciences have brought ever-increasing
      interests in combined therapies for better clinical efficacy and safety,
      especially in cases of complicated and refractory diseases. Innovative
      experimental technologies and theoretical frameworks are being actively developed
      for multicomponent drug research. In this work, we present the Drug Combination
      Database, with aims to facilitate analyses of known drug combinations, to
      summarize patterns of beneficial drug interactions, and to provide a basis for
      theoretical modeling and simulation of such drug interactions. Its current
      version (1.0) collected 499 approved or investigational drug combinations,
      including 40 unsuccessful drug combinations, involving 485 individual drugs, from
      >6000 references.

PMID- 20031965
TI  - Power to detect selective allelic amplification in genome-wide scans of tumor
      data.
AB  - MOTIVATION: Somatic amplification of particular genomic regions and selection of
      cellular lineages with such amplifications drives tumor development. However,
      pinpointing genes under such selection has been difficult due to the large span
      of these regions. Our recently-developed method, the amplification distortion
      test (ADT), identifies specific nucleotide alleles and haplotypes that confer
      better survival for tumor cells when somatically amplified. In this work, we
      focus on evaluating ADT's power to detect such causal variants across a variety
      of tumor dataset scenarios. RESULTS: Towards this end, we generated multiple
      parameter-based, synthetic datasets-derived from real data-that contain somatic
      copy number aberrations (CNAs) of various lengths and frequencies over germline
      single nucleotide polymorphisms (SNPs) genome-wide. Gold-standard causal sub
      regions were assigned within these CNAs, followed by an assessment of ADT's
      ability to detect these sub-regions. Results indicate that ADT possesses high
      sensitivity and specificity in large sample sizes across most parameter cases,
      including those that more closely reflect existing SNP and CNA cancer data.

PMID- 20031967
TI  - Penalized mixtures of factor analyzers with application to clustering high
      dimensional microarray data.
AB  - MOTIVATION: Model-based clustering has been widely used, e.g. in microarray data
      analysis. Since for high-dimensional data variable selection is necessary,
      several penalized model-based clustering methods have been proposed torealize
      simultaneous variable selection and clustering. However, the existing methods all
      assume that the variables are independent with the use of diagonal covariance
      matrices. RESULTS: To model non-independence of variables (e.g. correlated gene
      expressions) while alleviating the problem with the large number of unknown
      parameters associated with a general non-diagonal covariance matrix, we
      generalize the mixture of factor analyzers to that with penalization, which,
      among others, can effectively realize variable selection. We use simulated data
      and real microarray data to illustrate the utility and advantages of the proposed
      method over several existing ones.

PMID- 20031969
TI  - Predicting metabolic engineering knockout strategies for chemical production:
      accounting for competing pathways.
AB  - MOTIVATION: Computational modeling in metabolic engineering involves the
      prediction of genetic manipulations that would lead to optimized microbial
      strains, maximizing the production rate of chemicals of interest. Various
      computational methods are based on constraint-based modeling, which enables to
      anticipate the effect of genetic manipulations on cellular metabolism considering
      a genome-scale metabolic network. However, current methods do not account for the
      presence of competing pathways in a metabolic network that may diverge metabolic
      flux away from producing a required chemical, resulting in lower (or even zero)
      chemical production rates in reality-making these methods somewhat over
      optimistic. RESULTS: In this article, we describe a novel constraint-based method
      called RobustKnock that predicts gene deletion strategies that lead to the over
      production of chemicals of interest, by accounting for the presence of competing
      pathways in the network. We describe results of applying RobustKnock to
      Escherichia coli's metabolic network towards the production of various chemicals,
      demonstrating its ability to provide more robust predictions than those obtained
      via current state-of-the-art methods.

PMID- 20031968
TI  - CMDS: a population-based method for identifying recurrent DNA copy number
      aberrations in cancer from high-resolution data.
AB  - MOTIVATION: DNA copy number aberration (CNA) is a hallmark of genomic abnormality
      in tumor cells. Recurrent CNA (RCNA) occurs in multiple cancer samples across the
      same chromosomal region and has greater implication in tumorigenesis. Current
      commonly used methods for RCNA identification require CNA calling for individual
      samples before cross-sample analysis. This two-step strategy may result in a
      heavy computational burden, as well as a loss of the overall statistical power
      due to segmentation and discretization of individual sample's data. We propose a
      population-based approach for RCNA detection with no need of single-sample
      analysis, which is statistically powerful, computationally efficient and
      particularly suitable for high-resolution and large-population studies. RESULTS:
      Our approach, correlation matrix diagonal segmentation (CMDS), identifies RCNAs
      based on a between-chromosomal-site correlation analysis. Directly using the raw
      intensity ratio data from all samples and adopting a diagonal transformation
      strategy, CMDS substantially reduces computational burden and can obtain results
      very quickly from large datasets. Our simulation indicates that the statistical
      power of CMDS is higher than that of single-sample CNA calling based two-step
      approaches. We applied CMDS to two real datasets of lung cancer and brain cancer
      from Affymetrix and Illumina array platforms, respectively, and successfully
      identified known regions of CNA associated with EGFR, KRAS and other important
      oncogenes. CMDS provides a fast, powerful and easily implemented tool for the
      RCNA analysis of large-scale data from cancer genomes.

PMID- 20031970
TI  - Pandora, a pathway and network discovery approach based on common biological
      evidence.
AB  - MOTIVATION: Many biological phenomena involve extensive interactions between many
      of the biological pathways present in cells. However, extraction of all the
      inherent biological pathways remains a major challenge in systems biology. With
      the advent of high-throughput functional genomic techniques, it is now possible
      to infer biological pathways and pathway organization in a systematic way by
      integrating disparate biological information. RESULTS: Here, we propose a novel
      integrated approach that uses network topology to predict biological pathways. We
      integrated four types of biological evidence (protein-protein interaction,
      genetic interaction, domain-domain interaction and semantic similarity of Gene
      Ontology terms) to generate a functionally associated network. This network was
      then used to develop a new pathway finding algorithm to predict biological
      pathways in yeast. Our approach discovered 195 biological pathways and 31
      functionally redundant pathway pairs in yeast. By comparing our identified
      pathways to three public pathway databases (KEGG, BioCyc and Reactome), we
      observed that our approach achieves a maximum positive predictive value of 12.8%
      and improves on other predictive approaches. This study allows us to reconstruct
      biological pathways and delineates cellular machinery in a systematic view.

PMID- 20031971
TI  - Bisque: a platform for bioimage analysis and management.
AB  - MOTIVATION: Advances in the field of microscopy have brought about the need for
      better image management and analysis solutions. Novel imaging techniques have
      created vast stores of images and metadata that are difficult to organize,
      search, process and analyze. These tasks are further complicated by conflicting
      and proprietary image and metadata formats, that impede analyzing and sharing of
      images and any associated data. These obstacles have resulted in research
      resources being locked away in digital media and file cabinets. Current image
      management systems do not address the pressing needs of researchers who must
      quantify image data on a regular basis. RESULTS: We present Bisque, a web-based
      platform specifically designed to provide researchers with organizational and
      quantitative analysis tools for 5D image data. Users can extend Bisque with both
      data model and analysis extensions in order to adapt the system to local needs.
      Bisque's extensibility stems from two core concepts: flexible metadata facility
      and an open web-based architecture. Together these empower researchers to create,
      develop and share novel bioimage analyses. Several case studies using Bisque with
      specific applications are presented as an indication of how users can expect to
      extend Bisque for their own purposes.

PMID- 20031972
TI  - DR-Integrator: a new analytic tool for integrating DNA copy number and gene
      expression data.
AB  - SUMMARY: DNA copy number alterations (CNA) frequently underlie gene expression
      changes by increasing or decreasing gene dosage. However, only a subset of genes
      with altered dosage exhibit concordant changes in gene expression. This subset is
      likely to be enriched for oncogenes and tumor suppressor genes, and can be
      identified by integrating these two layers of genome-scale data. We introduce
      DNA/RNA-Integrator (DR-Integrator), a statistical software tool to perform
      integrative analyses on paired DNA copy number and gene expression data. DR
      Integrator identifies genes with significant correlations between DNA copy number
      and gene expression, and implements a supervised analysis that captures genes
      with significant alterations in both DNA copy number and gene expression between
      two sample classes. AVAILABILITY: DR-Integrator is freely available for non
      commercial use from the Pollack Lab at http://pollacklab.stanford.edu/ and can be
      downloaded as a plug-in application to Microsoft Excel and as a package for the R
      statistical computing environment. The R package is available under the name
      'DRI' at http://cran.r-project.org/. An example analysis using DR-Integrator is
      included as supplemental material. SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 20031973
TI  - Limited contribution of stem-loop potential to symmetry of single-stranded
      genomic DNA.
AB  - MOTIVATION: The phenomenon of strand symmetry, which may provide clues to genome
      evolution, exists in all prokaryotic and eukaryotic genomes studied. Several
      possible mechanisms for its origins have been proposed, including: no strand
      biases for mutation and selection, strand inversion and selection of stem-loop
      structures. However, the relative contributions of these mechanisms to strand
      symmetry are not clear. In this article, we studied specifically the role of stem
      loop potential of single-stranded DNA in strand symmetry. RESULTS: We analyzed
      the complete genomes of 90 prokaryotes. We found that most oligonucleotides
      (pentanucleotides and higher) do not have a reverse complement in close proximity
      in the genomic sequences. Combined with further analysis, we conclude that the
      contribution of the widespread stem-loop potential of single-stranded genomic DNA
      to the formation and maintenance of strand symmetry would be very limited, at
      least for higher-order oligonucleotides. Therefore, other possible causes for
      strand symmetry must be taken into account to a deeper degree.

PMID- 20031974
TI  - BRAT: bisulfite-treated reads analysis tool.
AB  - SUMMARY: We present a new, accurate and efficient tool for mapping short reads
      obtained from the Illumina Genome Analyzer following sodium bisulfite conversion.
      Our tool, BRAT, supports single and paired-end reads and handles input files
      containing reads and mates of different lengths. BRAT is faster, maps more unique
      paired-end reads and has higher accuracy than existing programs. The software
      package includes tools to end-trim low-quality bases of the reads and to report
      nucleotide counts for mapped reads on the reference genome.

PMID- 20031975
TI  - emPAI Calc--for the estimation of protein abundance from large-scale
      identification data by liquid chromatography-tandem mass spectrometry.
AB  - SUMMARY: emPAI Calc is an open-source web application for the estimation of
      protein abundance. It uses the correlation between the number of identified
      peptides and protein abundance in mass spectrometry-based proteomic experiments.
      The program is the first implementation of our previously reported emPAI
      algorithm; it calculates the emPAI from the protein identification results
      obtained by database search engines such as Mascot.

PMID- 20031976
TI  - The effects of body posture, anatomy, age and pregnancy on the calculation of
      induced current densities at 50 Hz.
AB  - This paper presents calculations of the induced current density in the body at 50
      Hz from applied electric and magnetic fields. An extensive ensemble of 25 voxel
      models has been used to investigate the effects of body posture, anatomy, age and
      pregnancy. This set includes six adult models, eight child models and seven
      pregnant female models at various stages of gestation. The four postures
      investigated in the HPA adult model, NORMAN, were the standard position with the
      arms at the side, with the arms vertically above the head, the arms horizontally
      to the side and sitting.

PMID- 20031978
TI  - Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree.
AB  - I discuss eukaryotic deep phylogeny and reclassify the basal eukaryotic kingdom
      Protozoa and derived kingdom Chromista in the light of multigene trees. I
      transfer the formerly protozoan Heliozoa and infrakingdoms Alveolata and Rhizaria
      into Chromista, which is sister to kingdom Plantae and arguably originated by
      synergistic double internal enslavement of green algal and red algal cells. I
      establish new subkingdoms (Harosa; Hacrobia) for the expanded Chromista. The
      protozoan phylum Euglenozoa differs immensely from other eukaryotes in its
      nuclear genome organization (trans-spliced multicistronic transcripts),
      mitochondrial DNA organization, cytochrome c-type biogenesis, cell structure and
      arguably primitive mitochondrial protein-import and nuclear DNA prereplication
      machineries. The bacteria-like absence of mitochondrial outer-membrane channel
      Tom40 and DNA replication origin-recognition complexes from trypanosomatid
      Euglenozoa roots the eukaryotic tree between Euglenozoa and all other eukaryotes
      (neokaryotes), or within Euglenozoa. Given their unique properties, I segregate
      Euglenozoa from infrakingdom Excavata (now comprising only phyla Percolozoa,
      Loukozoa, Metamonada), grouping infrakingdoms Euglenozoa and Excavata as the
      ancestral protozoan subkingdom Eozoa. I place phylum Apusozoa within the derived
      protozoan subkingdom Sarcomastigota. Clarifying early eukaryote evolution
      requires intensive study of properties distinguishing Euglenozoa from neokaryotes
      and Eozoa from neozoa (eukaryotes except Eozoa; ancestrally defined by haem
      lyase).

PMID- 20031979
TI  - Exposure to seismic survey alters blue whale acoustic communication.

PMID- 20031980
TI  - Young children with autism spectrum disorder use predictive eye movements in
      action observation.
AB  - Does a dysfunction in the mirror neuron system (MNS) underlie the social symptoms
      defining autism spectrum disorder (ASD)? Research suggests that the MNS matches
      observed actions to motor plans for similar actions, and that these motor plans
      include directions for predictive eye movements when observing goal-directed
      actions. Thus, one important question is whether children with ASD use predictive
      eye movements in action observation. Young children with ASD as well as typically
      developing children and adults were shown videos in which an actor performed
      object-directed actions (human agent condition). Children with ASD were also
      shown control videos showing objects moving by themselves (self-propelled
      condition). Gaze was measured using a corneal reflection technique. Children with
      ASD and typically developing individuals used strikingly similar goal-directed
      eye movements when observing others' actions in the human agent condition. Gaze
      was reactive in the self-propelled condition, suggesting that prediction is
      linked to seeing a hand-object interaction. This study does not support the view
      that ASD is characterized by a global dysfunction in the MNS.

PMID- 20031982
TI  - Is quality more important than quantity? Insect behavioural responses to changes
      in a volatile blend after stemborer oviposition on an African grass.
AB  - Plants subjected to insect attack usually increase volatile emission which
      attracts natural enemies and repels further herbivore colonization. Less is known
      about the capacity of herbivores to suppress volatiles and the multitrophic
      consequences thereof. In our study, the African forage grass, Brachiaria
      brizantha, was exposed to ovipositing spotted stemborer, Chilo partellus, moths.
      A marked reduction in emission of the main volatile, (Z)-3-hexenyl acetate
      (Z3HA), occurred following oviposition but the ratio of certain other minor
      component volatiles to Z3HA was increased. While further herbivore colonization
      was reduced on plants after oviposition, the new volatile profile caused
      increased attraction of an adapted parasitoid, Cotesia sesamiae. Our results show
      that insect responses are dependent on the quality of volatile emission rather
      than merely the quantity in this multitrophic interaction.

PMID- 20031983
TI  - Placing microalgae on the biofuels priority list: a review of the technological
      challenges.
AB  - Microalgae provide various potential advantages for biofuel production when
      compared with 'traditional' crops. Specifically, large-scale microalgal culture
      need not compete for arable land, while in theory their productivity is greater.
      In consequence, there has been resurgence in interest and a proliferation of
      algae fuel projects. However, while on a theoretical basis, microalgae may
      produce between 10- and 100-fold more oil per acre, such capacities have not been
      validated on a commercial scale. We critically review current designs of algal
      culture facilities, including photobioreactors and open ponds, with regards to
      photosynthetic productivity and associated biomass and oil production and include
      an analysis of alternative approaches using models, balancing space needs,
      productivity and biomass concentrations, together with nutrient requirements. In
      the light of the current interest in synthetic genomics and genetic
      modifications, we also evaluate the options for potential metabolic engineering
      of the lipid biosynthesis pathways of microalgae. We conclude that although
      significant literature exists on microalgal growth and biochemistry,
      significantly more work needs to be undertaken to understand and potentially
      manipulate algal lipid metabolism. Furthermore, with regards to chemical
      upgrading of algal lipids and biomass, we describe alternative fuel synthesis
      routes, and discuss and evaluate the application of catalysts traditionally used
      for plant oils. Simulations that incorporate financial elements, along with fluid
      dynamics and algae growth models, are likely to be increasingly useful for
      predicting reactor design efficiency and life cycle analysis to determine the
      viability of the various options for large-scale culture. The greatest potential
      for cost reduction and increased yields most probably lies within closed or
      hybrid closed-open production systems.

PMID- 20031984
TI  - Strontium borate glass: potential biomaterial for bone regeneration.
AB  - Boron plays important roles in many life processes including embryogenesis, bone
      growth and maintenance, immune function and psychomotor skills. Thus, the
      delivery of boron by the degradation of borate glass is of special interest in
      biomedical applications. However, the cytotoxicity of borate glass which arises
      with the rapid release of boron has to be carefully considered. In this study, it
      was found that the incorporation of strontium into borate glass can not only
      moderate the rapid release of boron, but also induce the adhesion of osteoblast
      like cells, SaOS-2, thus significantly increasing the cyto-compatibility of
      borate glass. The formation of multilayers of apatite with porous structure
      indicates that complete degradation is optimistic, and the spread of SaOS-2
      covered by apatite to form a sandwich structure may induce bone-like tissue
      formation at earlier stages. Therefore, such novel strontium-incorporated
      borosilicate may act as a new generation of biomaterial for bone regeneration,
      which not only renders boron as a nutritious element for bone health, but also
      delivers strontium to stimulate formation of new bones.

PMID- 20031985
TI  - The effectiveness of an air cleaner in controlling droplet/aerosol particle
      dispersion emitted from a patient's mouth in the indoor environment of dental
      clinics.
AB  - Dental healthcare workers (DHCWs) are at high risk of occupational exposure to
      droplets and aerosol particles emitted from patients' mouths during treatment. We
      evaluated the effectiveness of an air cleaner in reducing droplet and aerosol
      contamination by positioning the device in four different locations in an actual
      dental clinic. We applied computational fluid dynamics (CFD) methods to solve the
      governing equations of airflow, energy and dispersion of different-sized airborne
      droplets/aerosol particles. In a dental clinic, we measured the supply air
      velocity and temperature of the ventilation system, the airflow rate and the
      particle removal efficiency of the air cleaner to determine the boundary
      conditions for the CFD simulations. Our results indicate that use of an air
      cleaner in a dental clinic may be an effective method for reducing DHCWs'
      exposure to airborne droplets and aerosol particles. Further, we found that the
      probability of droplet/aerosol particle removal and the direction of airflow from
      the cleaner are both important control measures for droplet and aerosol
      contamination in a dental clinic. Thus, the distance between the air cleaner and
      droplet/aerosol particle source as well as the relative location of the air
      cleaner to both the source and the DHCW are important considerations for reducing
      DHCWs' exposure to droplets/aerosol particles emitted from the patient's mouth
      during treatments.

PMID- 20031986
TI  - Eyes are on us, but nobody cares: are eye cues relevant for strong reciprocity?
AB  - Strong reciprocity is characterized by the willingness to altruistically reward
      cooperative acts and to altruistically punish norm-violating, defecting
      behaviours. Recent evidence suggests that subtle reputation cues, such as eyes
      staring at subjects during their choices, may enhance prosocial behaviour. Thus,
      in principle, strong reciprocity could also be affected by eye cues. We
      investigate the impact of eye cues on trustees' altruistic behaviour in a trust
      game and find zero effect. Neither the subjects who are classified as prosocial
      nor the subjects who are classified as selfish respond to these cues. In sharp
      contrast to the irrelevance of subtle reputation cues for strong reciprocity, we
      find a large effect of explicit, pecuniary reputation incentives on the trustees'
      prosociality. Trustees who can acquire a good reputation that benefits them in
      future interactions honour trust much more than trustees who cannot build a good
      reputation. These results cast doubt on hypotheses suggesting that strong
      reciprocity is easily malleable by implicit reputation cues not backed by
      explicit reputation incentives.

PMID- 20031987
TI  - How rugged individualists enable one another to find food and shelter: field
      experiments with tropical hermit crabs.
AB  - Animals from invertebrates to humans benefit from information conspecifics make
      available, including information produced inadvertently. While inadvertent social
      information may frequently be exploited in nature, experiments have rarely been
      conducted in the wild to examine how such information helps animals in their
      natural ecology. Here I report a series of field experiments on free-living
      terrestrial hermit crabs (Coenobita compressus), showing how these asocial
      invertebrates learn the locations of their most essential resources, food and
      shelter, using inadvertent cues from conspecific competitors. Crabs have limited
      abilities to locate resources individually, but as they coalesce on a resource,
      their aggregation can be noticed by passing foragers, tipping them off about the
      discovery. Foragers were strongly attracted to experimentally simulated
      aggregations in which crabs were tethered to the same spot and in which the
      resources normally found beneath aggregations were excluded. Simulated
      aggregations of crabs whose shells were removed were likewise attractive, more
      than even these sought-after-shelters themselves. Experiments that simulated the
      chemical and visual cues of aggregations independently revealed that foragers
      oriented to aggregations primarily by sight, cueing in on the jostling
      competitive activity of the aggregation. Although crabs have not been selected to
      recruit others to newly discovered resources, their natural ecology has provided
      a setting where competitors regularly help one another by means of inadvertent
      social information.

PMID- 20031988
TI  - Climatic warming increases voltinism in European butterflies and moths.
AB  - Climate change is altering geographical ranges, population dynamics and
      phenologies of many organisms. For ectotherms, increased ambient temperatures
      frequently have direct consequences for metabolic rates, activity patterns and
      developmental rates. Consequently, in many insect species both an earlier
      beginning and prolongation of seasonal duration occurred in parallel with recent
      global warming. However, from an ecological and evolutionary perspective, the
      number of generations (voltinism) and investment into each generation may be even
      more important than seasonality, since an additional generation per unit time may
      accelerate population growth or adaptation. Using a dataset extending back to the
      mid-nineteenth century, I report changes in the voltinism of butterfly and moth
      species of Central Europe. A significant proportion of 263 multi-voltine species
      showed augmented frequency of second and subsequent generations relative to the
      first generation in a warm period since 1980, and 44 species even increased the
      number of generations after 1980. Expected ecological consequences are diverse.
      Since multi-voltinism has been linked to insect outbreaks they include an
      increase in the abundance of herbivorous pests of agriculture and forestry.
      However, disruption of the developmental synchrony associated with multi
      voltinism and host plant phenology may also reduce fitness, potentially having
      unexpected consequences for species of conservation concern. The ability of
      species to adapt evolutionarily to a changing environment may be facilitated by
      increased voltinism.

PMID- 20031990
TI  - Distributed leadership and adaptive decision-making in the ant Tetramorium
      caespitum.
AB  - In the ant species Tetramorium caespitum, communication and foraging patterns
      rely on group-mass recruitment. Scouts having discovered food recruit nestmates
      and behave as leaders by guiding groups of recruits to the food location. After a
      while, a mass recruitment takes place in which foragers follow a chemical trail.
      Since group recruitment is crucial to the whole foraging process, we investigated
      whether food characteristics induce a tuning of recruiting stimuli by leaders
      that act upon the dynamics and size of recruited groups. High sucrose
      concentration triggers the exit of a higher number of groups that contain twice
      as many ants and reach the food source twice as fast than towards a weakly
      concentrated one. Similar trends were found depending on food accessibility: for
      a cut mealworm, accessibility to haemolymph results in a faster formation of
      larger groups than for an entire mealworm. These data provide the background for
      developing a stochastic model accounting for exploitation patterns by group-mass
      recruiting species. This model demonstrates how the modulations performed by
      leaders drive the colony to select the most profitable food source among several
      ones. Our results highlight how a minority of individuals can influence
      collective decisions in societies based on a distributed leadership.

PMID- 20031989
TI  - Decline in top predator body size and changing climate alter trophic structure in
      an oceanic ecosystem.
AB  - Globally, overfishing large-bodied groundfish populations has resulted in
      substantial increases in their prey populations. Where it has been examined, the
      effects of overfishing have cascaded down the food chain. In an intensively
      fished area on the western Scotian Shelf, Northwest Atlantic, the biomass of prey
      species increased exponentially (doubling time of 11 years) even though the
      aggregate biomass of their predators remained stable over 38 years. Concomitant
      reductions in herbivorous zooplankton and increases in phytoplankton were also
      evident. This anomalous trophic pattern led us to examine how declines in
      predator body size (approx. 60% in body mass since the early 1970s) and climatic
      regime influenced lower trophic levels. The increase in prey biomass was
      associated primarily with declines in predator body size and secondarily to an
      increase in stratification. Sea surface temperature and predator biomass had no
      influence. A regression model explained 65 per cent of prey biomass variability.
      Trait-mediated effects, namely a reduction in predator size, resulted in a
      weakening of top predation pressure. Increased stratification may have enhanced
      growing conditions for prey fish. Size-selective harvesting under changing
      climatic conditions initiated a trophic restructuring of the food chain, the
      effects of which may have influenced three trophic levels.

PMID- 20031992
TI  - The dead do not lie: using skeletal remains for rapid assessment of historical
      small-mammal community baselines.
AB  - Conservation and restoration efforts are often hindered by a lack of historical
      baselines that pre-date intense anthropogenic environmental change. In this paper
      I document that natural accumulations of skeletal remains represent a potential
      source of high-quality data on the historical composition and structure of small
      mammal communities. I do so by assessing the fidelity of modern, decadal and
      centennial-scale time-averaged samples of skeletal remains (concentrated by
      raptor predation) to the living small-mammal communities from which they are
      derived. To test the power of skeletal remains to reveal baseline shifts, I
      employ the design of a natural experiment, comparing two taphonomically similar
      Great Basin cave localities in areas where anthropogenic land-use practices have
      diverged within the last century. I find relative stasis at the undisturbed site,
      but document rapid restructuring of the small-mammal community at the site
      subjected to recent disturbance. I independently validate this result using
      historical trapping records to show that dead remains accurately capture both the
      magnitude and direction of this baseline shift. Surveys of skeletal remains
      therefore provide a simple, powerful and rapid alternative approach for gaining
      insight into the historical structure and dynamics of modern small-mammal
      communities.

PMID- 20031991
TI  - Explosive eversion and functional morphology of the duck penis supports sexual
      conflict in waterfowl genitalia.
AB  - Coevolution of male and female genitalia in waterfowl has been hypothesized to
      occur through sexual conflict. This hypothesis raises questions about the
      functional morphology of the waterfowl penis and the mechanics of copulation in
      waterfowl, which are poorly understood. We used high-speed video of phallus
      eversion and histology to describe for the first time the functional morphology
      of the avian penis. Eversion of the 20 cm muscovy duck penis is explosive, taking
      an average of 0.36 s, and achieving a maximum velocity of 1.6 m s(-1). The
      collagen matrix of the penis is very thin and not arranged in an axial-orthogonal
      array, resulting in a penis that is flexible when erect. To test the hypothesis
      that female genital novelties make intromission difficult during forced
      copulations, we investigated penile eversion into glass tubes that presented
      different mechanical challenges to eversion. Eversion occurred successfully in a
      straight tube and a counterclockwise spiral tube that matched the chirality of
      the waterfowl penis, but eversion was significantly less successful into glass
      tubes with a clockwise spiral or a 135 degrees bend, which mimicked female
      vaginal geometry. Our results support the hypothesis that duck vaginal complexity
      functions to exclude the penis during forced copulations, and coevolved with the
      waterfowl penis via antagonistic sexual conflict.

PMID- 20031993
TI  - Vigilance against predators induced by eavesdropping on heterospecific alarm
      calls in a non-vocal lizard Oplurus cuvieri cuvieri (Reptilia: Iguania).
AB  - Prey animals can reduce their risk of predation by detecting potential predators
      before encounters occur. Some animals gain information about nearby predators by
      eavesdropping on heterospecific alarm calls. Despite having well-developed ears,
      most lizards do not use vocal information for intraspecific communication, and
      few studies have shown practical use of the ears in wild lizards. Here, we show
      that the Madagascan spiny-tailed iguana (Oplurus cuvieri cuvieri) obtains
      auditory signals for predator detection. The Madagascan spiny-tailed iguana and
      the Madagascar paradise flycatcher (Terpsiphone mutata) are syntopic inhabitants
      of the Ampijoroa dry deciduous forest of Madagascar. The iguana and the
      flycatcher have neither a predator-prey relationship nor resource competition,
      but they have shared predators such as raptors and snakes. Using playback
      experiments, we demonstrated that the iguana discriminates mobbing alarm calls of
      the flycatcher from its songs and then enhances its vigilance behaviour. Our
      results demonstrate the occurrence of an asymmetrical ecological relationship
      between the Madagascan spiny-tailed iguana and the paradise flycatcher through
      eavesdropping on information about the presence of predators. This implies that
      indirect interspecific interactions through information recognition may be more
      common than generally thought in an animal community.

PMID- 20031994
TI  - Sexual conflict and the gender load: correlated evolution between population
      fitness and sexual dimorphism in seed beetles.
AB  - Although males and females share much of the same genome, selection is often
      distinct in the two sexes. Sexually antagonistic loci will in theory cause a
      gender load in populations, because sex-specific selection on a given trait in
      one sex will compromise the adaptive evolution of the same trait in the other
      sex. However, it is currently not clear whether such intralocus sexual conflict
      (ISC) represents a transient evolutionary state, where conflict is rapidly
      resolved by the evolution of sexual dimorphism (SD), or whether it is a more
      chronic impediment to adaptation. All else being equal, ISC should manifest
      itself as correlated evolution between population fitness and SD in traits
      expressed in both sexes. However, comparative tests of this prediction are
      problematic and have been unfeasible. Here, we assess the effects of ISC by
      comparing fitness and SD across distinct laboratory populations of seed beetles
      that should be well adapted to a shared environment. We show that SD in juvenile
      development time, a key life-history trait with a history of sexually
      antagonistic selection in this model system, is positively related to fitness.
      This effect is due to a correlated evolution between population fitness and
      development time that is positive in females but negative in males. Loosening the
      genetic bind between the sexes has evidently allowed the sexes to approach their
      distinct adaptive peaks.

PMID- 20031995
TI  - Long-term outcomes of corrective osteotomy for the treatment of distal radius
      malunion.
AB  - Corrective osteotomy is an established but challenging treatment for distal
      radius malunion. Short- and intermediate-term results have been previously
      published while long-term results have not. The long-term results of 22 patients
      treated with corrective osteotomy for symptomatic distal radius malunion are
      presented (range 6-24 years, mean 13 years). All patients completed the DASH
      questionnaire and the modified Gartland and Werley, and Green and O'Brien scores
      postoperatively. Wrist alignment was assessed through standard wrist radiographs.
      Average wrist flexion-extension was 72.5% of the contralateral limb. Grip
      strength averaged 71%. The DASH score averaged 16 points corresponding to mild
      perceived disability. Results were categorized as fair on both the Gartland and
      Werley score (average 9 points) and the modified Green and O'Brien score (average
      67 points). Wrist alignment was maintained over time but 13 patients presented
      mild to moderate symptomatic wrist arthritis. The outcome presented may be a
      reflection of the use of stricter evaluation instruments or reflect the
      development of post-traumatic arthritis.

PMID- 20031996
TI  - Capitolunate arthrodesis maintaining carpal height for the treatment of SNAC
      wrist.
AB  - The clinical and radiological results of a modified midcarpal fusion technique
      for scaphoid nonunion advance collapse were retrospectively studied in eight
      patients. All had partial resection of the proximal part of the fractured
      scaphoid, limited radial styloidectomy, scaphocapitate and lunocapitate
      arthrodesis, using a block of iliac crest graft to maintain carpal height. All
      united without complications and wrist motion, grip strength and carpal height
      were improved postoperatively. The modified Mayo wrist score at follow-up was
      70%. Three patients continued to have some pain and one patient had a poor
      result.

PMID- 20031997
TI  - Long-term results following osteotomy of the thumb delta phalanx in Rubinstein
      Taybi Syndrome.
AB  - Rubinstein-Taybi Syndrome is a rare condition affecting 1:125,000 children. It is
      associated with short broad radially deviated thumbs, secondary to a delta
      proximal phalanx of the thumb. We undertook a retrospective review of seven
      children (13 thumbs) with Rubinstein-Taybi syndrome whose thumbs were treated
      using a corrective osteotomy to the delta phalanx over a 13 year period. The
      types of osteotomy used in the series were reverse wedge osteotomy, opening wedge
      osteotomy and dome shaped osteotomy. The mean preoperative radial deviation of
      thumbs was 68 degrees (range 45-85 degrees ). At follow up five of the 13 thumbs
      demonstrated some residual radial deviation. All recurrences occurred in the dome
      shaped osteotomy group. Our data suggest that surgery is effective in correcting
      the deformity, but there is a risk of incomplete correction or recurrence.
      Despite the recurrence the mean postoperative deformity was significantly better
      than preoperatively and the majority of patients families subjectively reported
      good function. No patient in our series has yet undergone further corrective
      surgery.

PMID- 20031998
TI  - Cut-off value for self-reported abnormal cold sensitivity and predictors for
      abnormality and severity in hand injuries.
AB  - Our aim was to identify a cut-off value for self-reported, abnormal cold
      sensitivity and to identify cold sensitivity predictors after hand injuries. The
      Cold Intolerance Symptom Severity (CISS) questionnaire and a VAS question
      concerning discomfort on exposure to cold were investigated in 94 normal people
      and 88 patients. A CISS score >50 was defined as abnormal cold sensitivity.
      Multiple injured digits, an increased number of injured vessels, complete nerve
      injury and replantation were variables associated with high VAS scores. Factors
      linked to both abnormality and worse CISS or VAS scores were: the presence of
      bone injury; a larger number of repaired vessels; the use of vascular grafts and
      a high Hand Injury Severity Score (HISS). The causes of abnormality and severity
      suggest a multifactorial aetiology with bony, vascular and neural components. A
      cut-off for abnormality is useful for descriptive, comparative and assessment
      purposes.

PMID- 20031999
TI  - Obstetric brachial plexus palsy: a comparison of affected infants delivered
      vaginally by breech or cephalic presentation.
AB  - In this retrospective study we compared obstetric brachial plexus palsy (OBPP) in
      two non-operated groups of newborn babies delivered vaginally by breech or
      cephalic presentation. There were 35 cases of OBPP in the breech group and 663
      cases in the cephalic group. The former group was more likely to develop upper
      Erb's palsy while the latter group was more likely to develop total palsy. The
      breech group also had a significantly lower mean birth weight, a significantly
      higher percentage of bilateral OBPP palsies and concurrent phrenic nerve palsy.
      Spontaneous recovery of shoulder abduction and elbow flexion in newborn babies
      with upper Erb's palsy was significantly worse in the breech compared with the
      cephalic group. It was concluded that OBPP following vaginal breech delivery has
      several unique demographic features and breech babies with upper Erb's palsy have
      a worse prognosis for spontaneous recovery than those in the cephalic group.

PMID- 20032000
TI  - Percutaneous retrograde screw fixation of non-displaced fractures of the scaphoid
      waist: an antirotation wire may not be necessary.
AB  - Some authors recommend using an antirotation wire when performing percutaneous
      screw fixation of acute non-displaced scaphoid waist fractures. The aim of this
      study of 21 cadaveric wrists was to assess the usefulness of such a wire in
      Herbert's B2-type fractures. A B2-type fracture was created experimentally on
      each scaphoid. An antirotation wire was inserted in eight wrists. Retrograde
      percutaneous fixation using a double-threaded headless cannulated screw was
      performed on all wrists. Computed tomography was used to measure interfragmentary
      rotation. No interfragmentary rotation was noted in either group. Our study
      suggests that using an antirotation wire may be unnecessary when performing
      retrograde percutaneous screw fixation of isolated B2-type scaphoid fractures.

PMID- 20032001
TI  - Hand and wrist malpractice claims in The Netherlands: 1993-2008.
AB  - We analysed hand and wrist injury and disorder related liability claims in the
      Netherlands to identify causes and to contribute to the prevention of such
      claims. Data was collected from 743 hand and wrist claims filed between 1993 and
      2007. Consultants were involved in 417 claims (56.1%). Treatment in the emergency
      department (ED) accounted for 64.9% of these 287 claims involved residents
      (59.5%). The majority of accepted claims in the ED included treatment by general
      surgeons (89.2%). The percentage of accepted claims was highest in the general
      surgery group (26.4%). Of accepted claims in the ED which involved a resident,
      93.2% involved a general surgery resident. Better training and supervision is
      indicated. This paper supports hand injury treatment by adequately trained
      surgeons and preferably, where possible, by a trained hand surgeon.

PMID- 20032002
TI  - Use of a medication control officer to reduce bias in a clinical trial: lessons
      learned from the scleroderma lung study.
AB  - BACKGROUND: Scleroderma Lung Study (SLS) was designed to evaluate the efficacy
      and safety of oral cyclophosphamide (CYC) versus placebo taken for 1 year for
      scleroderma-associated interstitial lung disease. An independent medication
      control officer (MCO), usually a physician, at each center was assigned to
      monitor laboratory and clinical toxicity of study medication and regulate its
      dosing based on these results. By having an MCO who watched and managed toxicity,
      the study investigators were free to care for study patients and to assess study
      outcomes without the potential bias of knowing toxicity data (toxicity from
      cyclophosphamide is distinctive - cytopenias and hematuria in particular).
      PURPOSE: To assess the usefulness of an MCO, whose chief role was to maintain
      safety while retaining the blinding in the clinical trial. METHODS: Patients had
      safety laboratory testing every 2-4 weeks and results were sent directly to the
      MCO within 2 days of the test. Other clinical adverse events (AEs) were reported
      by the patient to a nurse coordinator who reported them to the MCO who then
      managed the AEs to preserve the blinding of investigators caring for the
      patients. The MCO was provided pre-determined algorithms for dose adjustments of
      test medication based on the presence and severity of laboratory abnormalities.
      RESULTS: Safety monitoring by the MCO was effective in the early detection of
      drug toxicity with provision of appropriate medical intervention on a timely
      basis. At the same time, investigator blinding appeared to be maintained.
      LIMITATIONS: The testing of MCO effectiveness in maintaining blinding and
      consistency was not defined as an a priori hypothesis and thus complete data
      relating to the efficacy of the MCO were not collected in a prospective fashion.
      CONCLUSION: An MCO and pre-specified monitoring and dosing guidelines, coupled
      with uniform pre-specified responses to AEs, may be used effectively to preserve
      investigator blinding and provide consistency in response to AEs in a clinical
      trial setting, even when AEs of the test medication are distinctive.

PMID- 20032003
TI  - Providing reviews of evidence to COPD patients: qualitative study of barriers and
      facilitating factors to patient-mediated practice change.
AB  - This study aimed to identify barriers and facilitating factors to people with
      COPD performing the following actions: (a) reading a manual that contained
      summaries of evidence on treatments used in chronic obstructive pulmonary disease
      (COPD) and (b) at a medical consultation, asking questions that were provided in
      the manual and were designed to prompt doctors to review current treatments in
      the light of evidence. The manual was developed using current best practice and
      was designed to facilitate reading and discussion with doctors. In-depth
      interviews were held with patients who had received the manual. Of 125
      intervention participants from a controlled clinical trial of the manual, 16 were
      interviewed in their homes in and around Adelaide, South Australia. Plain
      language writing and a simple layout facilitated reading of the manual by
      participants. Where the content matched the interests of participants this also
      facilitated reading. On the other hand, some participants showed limited interest
      in the evidence summaries. Participant comments indicated that they did not see
      it as possible or acceptable for patients to master research evidence or initiate
      discussions of evidence with doctors. These appeared to be the main barriers to
      effectiveness of the manual. If evidence summaries for patients are to be used in
      disease management, they should be understandable and relevant to patients and
      provide a basis for discussion between patients and doctors. Work is now needed
      so that we can both present evidence summaries in a way that is relevant to
      patients and reduce the barriers to patient-initiated discussions of evidence.

PMID- 20032004
TI  - Much ado about next to nothing: incorporating nondetects in science.
AB  - A great many papers and one textbook have been published on the topic of how to
      incorporate 'nondetects', low-level values reported only as below a detection
      limit, into statistical analyses. This is of interest not only in occupational
      hygiene but also in environmental sciences and astronomy, among other fields.
      Here, the literature is reviewed from the earliest known publication on the topic
      >40 years ago and recommendations contrasted. I have tried to pull some unifying
      conclusions out of the mix, ending with four suggestions I believe all can agree
      on. See if you agree with me.

PMID- 20032005
TI  - Evaluation of the genotoxic and anti-genotoxic activities of silybin in human
      hepatoma cells (HepG2).
AB  - Silybin (SB), a constituent of the medicinal plant Silybum marianum, is reported
      to be a potent hepatoprotective agent, but little is currently known regarding
      its genotoxicity, mutagenicity and potential chemopreventive properties. In this
      study, we evaluated the ability of SB to induce DNA migration and micronuclei
      (MN) formation in human hepatoma cells (HepG2). Also, possible preventive effects
      of SB on MN formation induced by three different mutagens, bleomycin (BLEO),
      benzo[a]pyrene (B[a]P) and aflatoxin B(1) (AFB(1)), were studied. To clarify the
      possible mechanism of SB antimutagenicity, three treatment protocols were
      applied: pretreatment, in which SB was added before the application of the
      mutagens; simultaneous treatment, in which SB was added during treatment and post
      treatment, in which SB was added after the application of the mutagens. At
      concentrations up to 100 microM, SB was non-genotoxic, while at a concentration
      of 200 microM, SB induced DNA migration, generated oxidized DNA bases, reduced
      cell viability, decreased the replicative index of the cells and induced
      oxidative stress. It is noteworthy that SB was able to reduce the genotoxic
      effect induced by B[a]P, BLEO and AFB(1) in pretreatment and simultaneous
      treatments but had no significant effect on DNA damage induction in post
      treatment. Taken together, our findings indicate that SB presents anti-genotoxic
      activity in vitro, which suggests potential use as a chemopreventive agent.

PMID- 20032006
TI  - Hepatic safety profile of raltegravir in HIV-infected patients with chronic
      hepatitis C.
AB  - BACKGROUND: Patients with chronic hepatitis C virus (HCV) infection experience
      antiretroviral-associated liver toxicity more frequently than HIV mono-infected
      persons. Herein, we report the hepatic safety profile of raltegravir in a
      relatively large group of HIV/HCV co-infected patients, a population that was
      poorly represented in the registrational studies. METHODS: Prospective,
      observational study of all antiretroviral-experienced HIV-infected patients who
      initiated raltegravir from January 2006 to January 2009 at a reference HIV
      clinic. Clinical data, laboratory parameters and liver stiffness measured at
      baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis
      C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined
      following the AIDS Clinical Trials Group definition for liver enzyme elevations
      (LEEs). A control group of patients who initiated protease inhibitors (PIs) or
      non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly.
      RESULTS: Data from 218 HIV-infected patients on raltegravir were analysed, 126
      HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs
      occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients
      (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe
      hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co
      infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three
      subjects other reasons than raltegravir exposure most likely explained LEEs.
      Multivariate analysis revealed HCV co-infection as the only independent variable
      associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally,
      the rate of LEEs in patients on raltegravir was lower than in those who were
      treated with PIs or NNRTIs. CONCLUSIONS: LEEs are less frequent in patients
      treated with raltegravir than with other antiretroviral drug classes. However,
      HIV/HCV co-infected patients treated with raltegravir experienced LEEs more
      frequently than HIV mono-infected persons. In this series, LEEs in patients
      treated with raltegravir were uniformly mild and no cases of grade 3-4
      hepatotoxicity could be directly attributed to the drug. These results reinforce
      the overall hepatic safety profile of raltegravir.

PMID- 20032007
TI  - Co-administration of fluconazole increases nevirapine concentrations in HIV
      infected Ugandans.
AB  - BACKGROUND: Data from retrospective studies have suggested that there may be an
      interaction between fluconazole and nevirapine, increasing nevirapine
      concentrations and potentially leading to hepatotoxicity. METHODS: This study was
      nested within a large double-blind placebo-controlled study designed to determine
      if primary prophylaxis with fluconazole (200 mg three times per week) could
      reduce cryptococcal disease [CRYPTOPRO (ISRCTN 76481529)] in HIV-infected adults
      in rural south-western Uganda. Detailed pharmacokinetic studies were performed on
      49 participants (22 on placebo and 27 on fluconazole) who had been on fluconazole
      or placebo with nevirapine for > or =4 weeks. RESULTS: The geometric mean pre
      dose concentrations of nevirapine were 3865 ng/mL [95% confidence interval (95%
      CI) 3452-4758 ng/mL] and 5141 ng/mL (95% CI 4760-6595 ng/mL) (P = 0.009) in the
      placebo and fluconazole arms, respectively. The change in the peak nevirapine
      concentration in plasma (C(max)) was also higher in the fluconazole arm compared
      with the placebo arm [median 6546 (95% CI 6040-7974) versus 5126 (95% CI 4739
      5773) ng/mL, P = 0.012]. Fluconazole increased the nevirapine area under the
      curve (AUC) from 0 to 8 h by 29% [geometric mean AUC(0-8) 46 135 (95% CI 42 432
      57 173) versus 35 871 (95% CI 32 808-41 372) ng.h/mL, P = 0.016]. In the larger
      cohort from which the participants were drawn, co-administration of fluconazole
      did not increase the risk of hepatotoxicity. CONCLUSIONS: Fluconazole led to
      significant increases in nevirapine exposure, but was not associated with
      evidence of increased hepatotoxicity.

PMID- 20032008
TI  - The role of oestrogen receptor {alpha} in human thyroid cancer: contributions
      from coregulatory proteins and the tyrosine kinase receptor HER2.
AB  - Epidemiological, clinical, and molecular studies suggest a role for oestrogen in
      thyroid cancer. How oestrogen mediates its effects and the consequence of it on
      clinical outcome has not been fully elucidated. The participation of coregulatory
      proteins in modulating oestrogen receptor (ER) function and input of crosstalk
      with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell
      proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the
      anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor
      coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell
      proliferation. Oestrogen also increased protein expression of SRC-1 and the ER
      target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory
      proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor
      HER2 were localised by immunohistochemistry and immnofluorescence in paraffin
      embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised
      with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression
      of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was
      significantly associated with well-differentiated tumours and reduced incidence
      of disease recurrence. In non-anaplastic tumours, HER2 was significantly
      associated with SRC-1, and these proteins were associated with poorly
      differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of
      anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease
      free survival indicated that in thyroid cancer, SRC-1 strongly correlates with
      reduced disease-free survival (P<0.001), whereas NCoR predicted increased
      survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1
      and NCoR in thyroid tumour progression.

PMID- 20032009
TI  - Are smokers with acute cough in primary care prescribed antibiotics more often,
      and to what benefit? An observational study in 13 European countries.
AB  - Little is known about actual clinical practice regarding management of smokers
      compared with ex-smokers and nonsmokers presenting with acute cough in primary
      care, and whether a lower threshold for prescribing antibiotics benefits smokers.
      This was a multicentre 13-country European prospective observational study of
      primary care clinician management of acute cough in consecutive immunocompetent
      adults presenting with an acute cough of <or=28 days duration. There was complete
      smoking status data for 2,549 out of 3,402 participants. 28% were smokers, 24% ex
      smokers and 48% nonsmokers. Smokers and ex-smokers had more chronic respiratory
      conditions (18.5% and 20.5% versus 12.5%). Median symptom severity scores were
      similar. Smokers were prescribed antibiotics more frequently (60%) than ex
      smokers (51%) and nonsmokers (53%). After adjusting for clinical presentation and
      patient characteristics, the odds ratio of being prescribed antibiotics for
      smokers compared with nonsmokers was 1.44 (95% CI 1.12-1.86; p = 0.005). Patient
      recovery was not significantly different for smokers and nonsmokers, after
      adjusting for clinical presentation and patient characteristics. Smoking status
      was used as an independent factor to determine whether or not to prescribe an
      antibiotic. Being prescribed an antibiotic was not associated with recovery in
      smokers.

PMID- 20032010
TI  - 17q21 variants modify the association between early respiratory infections and
      asthma.
AB  - Single nucleotide polymorphisms (SNPs) at chromosome 17q21 confer an increased
      risk of early-onset asthma. The objective was to study whether 17q21 SNPs modify
      associations between early respiratory infections and asthma. Association
      analysis was conducted in 499 children (268 with asthma, median age 11 yrs) from
      the Epidemiological Study on the Genetics and Environment of Asthma (EGEA). The
      12-yr follow-up data were used to assess persistent or remittent asthma in young
      adulthood. Respiratory infection before 2 yrs of age was assessed
      retrospectively. For the 12 17q21 SNPs studied, the odds ratios (OR) for
      association between infection and early-onset asthma (age at onset <or=4 yrs)
      were higher in carriers of risk genotypes (OR 3.42-6.36) than in noncarriers (OR
      1.84-2.44; p-value for interaction 0.02-0.04 for five SNPs). Risk genotypes also
      increased the association between infection and childhood asthma that remits in
      adulthood (OR 4.84-7.16 in carriers and 1.74-2.25 in noncarriers; p-value for
      interaction 0.008-0.05 for 10 SNPs). In children with 17q21 risk genotypes and
      early-life environmental tobacco smoke (ETS) exposure, associations between
      infection and asthma were further enhanced. 17q21 genetic variants and early ETS
      exposure enhance the association between early respiratory infections and early
      onset asthma and childhood asthma that remits in adulthood.

PMID- 20032011
TI  - Different definitions in childhood asthma: how dependable is the dependent
      variable?
AB  - There is abundant literature on how to select and statistically deal with
      predictors in prediction models. Less attention has been paid to the choice of
      the outcome. We assessed the impact of different asthma definitions on prevalence
      estimates and on the prediction model's performances. We searched PubMed and
      extracted data of definitions used to diagnose childhood asthma (between 6 and 18
      yrs) in cohort studies. Next, using data from an ongoing cohort study (n = 186),
      we constructed and compared four prediction models which all predict asthma at
      age 6 yrs, using a fixed set of predictors and four different definitions in
      turn. We defined an area of clinical indecision (posterior probability between
      25% and 60%) and calculated the number of children who remained inside this area.
      122 papers yielded 60 different definitions. Prevalence estimates varied between
      15.1% and 51.1% depending on the asthma definition used. The percentage of
      children whose posterior asthma probability was in the area of clinical
      indecision varied from 14.9% to 65.3%. Variation in definitions and its effect on
      the performance of prediction models may be another source of otherwise
      inexplicable variation in daily clinical decision making. More uniformity of
      operational asthma definitions seems needed.

PMID- 20032012
TI  - Effects of pentobarbital on upper airway patency during sleep.
AB  - We hypothesised that pentobarbital would improve upper airway mechanics based on
      an increase in latency to arousal and amplitude of the phasic genioglossus
      electromyogram (EMG), and a decrease in the active upper airway critical closing
      pressure (P(crit)). 12 healthy subjects received pentobarbital (100 mg) or
      placebo in a double-blind, crossover protocol. During wakefulness, we measured
      the genioglossus reflex response to negative pressure pulses. During sleep,
      carbon dioxide was insufflated into the inspired air. Airway pressure was then
      decreased in a stepwise fashion until arousal from sleep. With basal breathing
      during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal
      CO(2) concentration and upper airway resistance were greater; and P(crit) was
      unaffected (pentobarbital mean +/- SD -11.7 +/- 4.5 versus placebo -10.25 +/- 3.6
      cmH(2)O; p = 0.11). Pentobarbital increased the time to arousal (297 +/- 63s
      versus 232 +/- 67 s; p<0.05), at which time phasic genioglossus EMG was higher
      (6.2 +/- 4.8% maximal versus 3.1 +/- 3%; p<0.05) as were CO(2) levels. The
      increase in genioglossus EMG after CO(2) administration was greater after
      pentobarbital versus placebo. Pentobarbital did not affect the genioglossus
      negative-pressure reflex. Pentobarbital increases the time to arousal and
      stimulates genioglossus muscle activity, but it also increases upper airway
      resistance during sleep.

PMID- 20032013
TI  - Identification of novel susceptibility genes in ozone-induced inflammation in
      mice.
AB  - Ozone (O(3)) remains a prevalent air pollutant and public health concern. Inf2 is
      a significant quantitative trait locus on murine chromosome 17 that contributes
      to susceptibility to O(3)-induced infiltration of polymorphonuclear leukocytes
      (PMNs) into the lung, but the mechanisms of susceptibility remain unclear. The
      study objectives were to confirm and restrict Inf2, and to identify and test
      novel candidate susceptibility gene(s). Congenic strains of mice that contained
      overlapping regions of Inf2 and their controls, and mice deficient in either
      major histocompatibility complex (MHC) class II genes or the Tnf cluster, were
      exposed to air or O(3). Lung inflammation and gene expression were assessed. Inf2
      was restricted from 16.42 Mbp to 0.96 Mbp, and bioinformatic analysis identified
      MHC class II, the Tnf cluster and other genes in this region that contain
      potentially informative single nucleotide polymorphisms between the susceptible
      and resistant mice. Furthermore, O(3)-induced inflammation was significantly
      reduced in mice deficient in MHC class II genes or the Tnf cluster genes,
      compared with wild-type controls. Gene expression differences were also observed
      in MHC class II and Tnf cluster genes. This integrative genetic analysis of Inf2
      led to identification of novel O(3) susceptibility genes that may provide
      important, new therapeutic targets in susceptible individuals.

PMID- 20032014
TI  - c-ANCA-induced neutrophil-mediated lung injury: a model of acute Wegener's
      granulomatosis.
AB  - Anti-neutrophil cytoplasmic antibodies (c-ANCA) targeting proteinase 3 (PR3) are
      implicated in the pathogenesis of Wegener's granulomatosis (WG). Fulminant
      disease can present as acute lung injury (ALI). In this study, a model of ALI in
      WG was developed using isolated rat lungs. Isolated human polymorphonuclear
      leukocytes (PMNs) were primed with tumour necrosis factor (TNF) to induce surface
      expression of PR3. Co-perfusion of TNF-primed neutrophils and monoclonal anti-PR3
      antibodies induced a massive weight gain in isolated lungs. This effect was not
      observed when control immunoglobulin G was co-perfused with TNF-primed PMNs. The
      c-ANCA-induced oedema formation was paralleled by an increase in the capillary
      filtration coefficient as a marker of increased pulmonary endothelial
      permeability. In contrast, pulmonary artery pressure was not affected. In the
      presence of the oxygen radical scavenger superoxide dismutase and a NADPH oxidase
      inhibitor, c-ANCA-induced lung oedema could be prevented. Inhibition of
      neutrophil elastase was equally effective in preventing c-ANCA-induced lung
      injury. In conclusion, anti-PR3 antibodies induced neutrophil mediated, elastase-
      and oxygen radical-dependent ALI in the isolated lung. This experimental model
      supports the hypothesis of a pathogenic role for c-ANCA in WG and offers the
      possibility of the development of therapeutic strategies for the treatment of
      lung injury in fulminant WG.

PMID- 20032015
TI  - Reference ranges for interrupter resistance technique: the Asthma UK Initiative.
AB  - Measuring interrupter resistance (R(int)) is an increasingly popular lung
      function technique and especially suitable for preschool children because it is
      simple, quick and requires only passive cooperation. A European Respiratory
      Society (ERS)/American Thoracic Society (ATS) Task Force recently published
      empirical recommendations related to procedures, limitations and interpretation
      of the technique. However, for valid interpretation, high-quality reference
      equations are required and these have been lacking. The aim of the present study
      was to collate R(int) data from healthy children in order to produce more robust
      reference equations. A further aim was to examine the influence of methodological
      differences on predicted R(int) values. R(int) data from healthy children were
      collected from published and unpublished sources. Reference equations for
      expiratory and inspiratory R(int) were developed using the LMS (lambda, mu,
      sigma) method. Data from 1,090 children (51% males) aged 3-13 yrs were collated
      to construct sex-specific reference equations for expiratory R(int) and data from
      629 children (51% males) were collated for inspiratory R(int). Height was the
      best independent predictor of both expiratory and inspiratory R(int). Differences
      between centres were clinically irrelevant, and differences between ethnic groups
      could not be examined. The availability of a large and generalisable sample and
      the use of modern statistical techniques enabled the development of more
      appropriate reference equations for R(int) in young children.

PMID- 20032016
TI  - Macrophage activation in exacerbated COPD with and without community-acquired
      pneumonia.
AB  - In large series of nonresponding community-acquired pneumonia (CAP) patients,
      chronic obstructive pulmonary disease (COPD) was observed to be a protective
      factor for nonresponse to initial antibiotics. This intriguing fact may be linked
      to changes in the phenotype of inflammatory cells and, in particular, to the
      induction of classical-M1 or alternative-M2 activation of macrophages, which
      result in different inflammatory profiles. We evaluated the effect of sputum
      obtained from patients with acute exacerbation of COPD (AECOPD), CAP and COPD+CAP
      on the phenotypic changes in macrophages. Human THP1 cells differentiated to
      macrophages were incubated with sputum from patients with AECOPD, CAP or
      COPD+CAP, and expression of tumour necrosis factor-alpha, interleukin-6, mannose
      receptor and arginase was measured to evaluate the phenotype acquired by
      macrophages. We found that sputum from CAP patients induced the M1 phenotype and
      that from AECOPD patients induced an M2-like phenotype. Sputum from CAP+COPD
      patients did not present a clear M1 or M2 phenotype. These results indicate that
      the microenvironment in the lung modulates the activation of macrophages,
      resulting in different phenotypes in AECOPD, CAP and COPD+CAP patients. This
      different type of activation induces different inflammatory responses and may be
      involved in the different outcome observed when COPD and CAP present
      simultaneously.

PMID- 20032017
TI  - Gas cooking is associated with small reductions in lung function in children.
AB  - Inconsistent effects of gas cooking on lung function have been reported. In a
      previous study from Austria, we demonstrated a significant, though small,
      reduction of lung function parameters in children living in homes with gas
      stoves. We used a larger international database to check if this finding can be
      generalised. To study the relative impact of cooking with gas on lung function
      parameters of primary school children in a wide range of geographical settings,
      we analysed flow and volume data of approximately 24,000 children (aged 6-12 yrs)
      from nine countries in Europe and North America. Exposure information was
      obtained by comparable questionnaires and spirometry according to an American
      Thoracic Society/European Respiratory Society protocol. Linear regressions were
      used, controlling for individual risk factors and study area. Heterogeneity
      between study-specific results and mean effects were estimated using meta
      analytical tools. On average, gas cooking reduced lung function parameters.
      Overall effects were small (-0.1-0.7%) and only significant for forced vital
      capacity and forced expiratory volume in 1 s. There was some indication that
      allergic children were more affected by gas cooking. Under current housing
      conditions, gas cooking is associated with only small reductions in lung
      function.

PMID- 20032018
TI  - Health effects of a subway environment in healthy volunteers.
AB  - Environmental particle exposure, often estimated as the particulate mass of
      particles with a diameter <10 microm, <2.5 microm or <1 microm (PM(10), PM(2.5)
      or PM(1)), is known to have a negative impact on the health of the population.
      Little is known about how the size and origin of particles influence the effects.
      We have previously shown that exposure to a road tunnel environment causes a
      cellular inflammatory response in the airways of healthy individuals. In the
      present study, our aim was to investigate potential airway health effects from
      exposure to a subway environment. 20 healthy volunteers were exposed to a subway
      and a control environment for 2 h, followed by measurements of lung function and
      the inflammatory response in the lower airways (bronchoscopy) and in the
      peripheral blood. No cellular response was found in the airways after exposure to
      the subway environment. In the blood, we found a statistically significant
      increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway
      and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst
      the concentrations of ultrafine particles, nitrogen monoxide and dioxide are
      lower in the subway. Although no cellular response was detected, the findings
      indicate a biological response to the subway environment. Our studies show that
      using gravimetric estimates of ambient particulate air pollution alone may have
      clear limitations in health-risk assessment.

PMID- 20032019
TI  - Of mice and men: comparative proteomics of bronchoalveolar fluid.
AB  - We hypothesised that comparing the protein mixture in bronchoalveolar lavage
      fluid (BALF) between humans and mice may lead to mechanistic insights into common
      and divergent pathways that evolved in each species. BALF from four humans and
      six mice was pooled separately and underwent identical shotgun proteomic
      analysis. Functional and network analysis was applied to identify overlapping and
      distinct pathways enriched in the BALF. Follow-up experiments using Western
      analysis in unpooled BALF samples were performed. We identified 91 unique
      proteins in human and 117 unique proteins in mouse BALF samples. Functional
      analysis of the proteins revealed conservation of several key processes between
      the species, including defence response. Oxidative stress response, however, was
      selectively enriched only in mouse BALF. Differences in the expression of
      peroxiredoxin-1, a key member of the defence pathway against oxidative injury,
      were confirmed between normal human and mouse BALF and in models of lung injury.
      A computational proteomics approach of mouse and human BALF confirms the
      conservation of immune and defence-mediated pathways while highlighting
      differences in response to oxidative stress. These observations suggest that the
      use of mice models to study human lung disorders should be undertaken with an
      appreciation of interspecies variability.

PMID- 20032020
TI  - Survival in pulmonary arterial hypertension: a reappraisal of the NIH risk
      stratification equation.
AB  - The aim of the present study was to determine contemporary survival in pulmonary
      arterial hypertension (PAH), and to investigate whether or not the National
      Institutes of Health (NIH) equation remains an accurate predictor of survival. In
      576 patients with PAH referred during 1991-2007, observed survival was described
      using the Kaplan-Meier method. In patients with idiopathic, familial and
      anorexigen-associated PAH (n = 247), observed versus NIH equation predicted
      survival was compared. A new survival prediction equation was developed using
      exponential regression analysis. The observed 1-, 3- and 5-yr survival in the
      total cohort were 86, 69 and 61%, respectively. In patients with idiopathic,
      familial and anorexigen-associated PAH, the observed 1-, 3- and 5-yr survival
      (92, 75 and 66%, respectively) were significantly higher than the predicted
      survival (65, 43 and 32%, respectively). The new equation (P(t) = e(-A(x,y,z)t),
      where P(t) is probability of survival, t the time interval in years, A(x,y,z) =
      e((-1.270-0.0148x+0.0402y-0.361z)), x the mean pulmonary artery pressure, y the
      mean right atrial pressure and z the cardiac index) performed well when applied
      to published contemporary studies of survival in PAH. Contemporary survival in
      the PAH cohort was better than that predicted by the NIH registry equation. The
      NIH equation underestimated survival in idiopathic, familial and anorexigen
      associated PAH. Once prospectively validated, the new equation may be used to
      determine prognosis.

PMID- 20032021
TI  - Adaptive servoventilation in diastolic heart failure and Cheyne-Stokes
      respiration.
AB  - A high prevalence of nocturnal Cheyne-Stokes respiration (CSR) has been
      documented in patients with heart failure with normal left ventricular ejection
      fraction (HFNEF). The aim of the present study was to investigate the effects of
      adaptive servoventilation (ASV) for treatment of CSR in these patients. In 60
      patients with HFNEF, defined according to current European Society of Cardiology
      guidelines, CSR was documented by polysomnography (apnoea/hypopnoea index (AHI)
      of >15 events x h(-1)). ASV treatment was offered to all patients; 21 initially
      rejected treatment, withdrew from treatment or presented noncompliant during
      follow-up (controls), whereas ongoing ASV therapy was initiated in 39 patients
      (ASV group). Echocardiography, cardiopulmonary exercise testing and measurement
      of N-terminal-pro-brain natriuretic peptide were performed at baseline and follow
      up (11.6+/-3 months). ASV therapy led to a significant reduction in AHI, longest
      apnoea and hypopnoea length, maximum and mean oxygen desaturation by pulse
      oximetry, percentage of study time with an oxygen saturation of <90% and arousal
      index. In addition, significant positive effects could be confirmed on absolute
      and predicted peak oxygen consumption, oxygen consumption at the individual
      aerobic-anaerobic threshold, oxygen pulse, as well as left atrial size, and
      transmitral flow patterns (mean early diastolic lengthening velocity and the
      ratio of peak early Doppler mitral inflow velocity to this lengthening velocity).
      ASV effectively attenuates CSR in patients with HFNEF and improves heart failure
      symptoms and cardiac function. Whether or not this is accompanied by an improved
      prognosis remains to be determined.

PMID- 20032022
TI  - Muscle dysfunction and exercise limitation in adolescent idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) can lead to ventilatory restriction,
      respiratory muscle weakness and exercise limitation. However, both the causes and
      the extent of muscle dysfunction remain unclear. The aim of our study is to
      describe muscle weakness and its relationship to lung function and tolerance to
      exercise in AIS patients. Lung and muscle function, together with exercise
      capacity, were assessed in 60 patients with pronounced spinal deformity (>40
      degrees) and in 25 healthy volunteers. Patients with AIS had only mild to
      moderate abnormal ventilatory patterns, the most frequent of which were
      restrictive abnormalities. The function of respiratory and limb muscles and
      exercise capacity were below normal limits in AIS patients, and were
      significantly lower than in controls. Exercise capacity was found to correlate
      with the function of inspiratory, expiratory, upper limb and lower limb muscles
      which, in addition, were reciprocally interrelated. Multivariate analysis showed
      that lower limb muscle function is the main contributor to exercise intolerance.
      There appeared to be no connection between spinal deformity and lung function,
      muscle function or exercise capacity. We conclude that AIS patients show
      generalised muscle dysfunction which contributes to the reduction in their
      exercise capacity, even in the absence of severe ventilatory impairment.

PMID- 20032023
TI  - Chloral hydrate sedation in term and preterm infants: an analysis of efficacy and
      complications.
AB  - BACKGROUND: Term and preterm infants are at risk of developing apnea after
      receiving general anesthesia. The risk of apnea after sedation with chloral
      hydrate (CH) in this population is unknown. In this study, we aimed to describe
      the clinical course of infants younger than 1 year who received CH for magnetic
      resonance imaging (MRI), with regard to the efficacy of CH sedation, the need for
      additional sedative drugs, and the incidence of oxyhemoglobin desaturation or
      need for oxygen supplementation. We aimed to determine the relationship between
      these factors to chronological age in term infants and gestational and
      postconceptional age (PCA) in preterm infants (<37 weeks' gestation). METHODS:
      This was a retrospective cohort study of 1394 infants undergoing MRI examination
      with CH sedation. Infants with an endotracheal tube, tracheostomy tube, or
      congenital heart disease were excluded. Patient charts were examined in detail to
      determine independent risk factors and dependent outcome variables up to 24 hours
      after MRI. Univariate and multivariate analyses were performed to determine risk
      factors for outcome variables. RESULTS: Postprocedure oxyhemoglobin desaturation
      was more likely in inpatients (P < 0.001) and was associated with a lower body
      weight (3.9 +/- 2.1 kg vs 6.6 +/- 3.0 kg; P < 0.001), history of apnea (33.3% vs
      9.9%; P = 0.001), higher ASA physical status (P = 0.002), and younger
      chronological age (58.7 +/- 82.8 days vs 152 +/- 105.9 days; P < 0.0001). When
      the preterm group was analyzed separately, the risk of postprocedure
      oxyhemoglobin desaturation was directly correlated with younger chronological age
      (56.0 +/- 41.5 days vs 150.6 +/- 107.1 days; P = 0.012) and younger PCA (39.5 +/-
      4.1 weeks vs 54.4 +/- 15.2 weeks; P = 0.005), but not gestational age. Preterm
      infants had more postprocedure bradycardia than term infants (P = 0.005).
      Postprocedural oxyhemoglobin desaturation was not seen in preterm infants older
      than 48 weeks' PCA. Because of the relatively small percentage of cases (8 of
      262) of postprocedural oxyhemoglobin desaturation in preterm infants, we were not
      able to definitively determine the difference in incidence between preterm and
      term infants. Additional doses of CH or supplementation with midazolam did not
      increase the incidence of complications. CONCLUSIONS: The occurrence of
      postprocedural oxyhemoglobin desaturation was directly correlated with younger
      chronological age in term infants and younger PCA in preterm infants. Term
      infants who required extended oxygen supplementation were inpatients and had
      significant comorbidities.

PMID- 20032024
TI  - What's new in obstetric anesthesia: the 2009 Gerard W. Ostheimer lecture.
AB  - This article summarizes the most relevant publications in obstetric
      anesthesiology from 2008. Forty-two articles were selected from a pool of several
      thousand in >70 English-language journals that were deemed as having the most
      impact on the practice of obstetric anesthesia.

PMID- 20032025
TI  - The diverse effects of vasopressors on the fetoplacental circulation of the dual
      perfused human placenta.
AB  - BACKGROUND: We studied the effects of 5 vasopressors on fetal arterial perfusion
      pressure (FAP) in vitro using the dual perfused, single isolated cotyledon, human
      placental model. METHODS: In 29 separate experiments, epinephrine (75 mg),
      norepinephrine (75 mg), ephedrine (50 mg), phenylephrine (2 mg), and methoxamine
      (40 mg) were introduced into the 250-mL reservoir serving the maternal perfusion
      circuit to determine the effect of each drug on FAP. The duration of drug
      exposure for each placental cotyledon was approximately 180 minutes. RESULTS:
      After 180 minutes, FAP (mean +/- sd) increased significantly with ephedrine from
      64 +/- 3 to 172 +/- 71 mm Hg (P < 0.001) and with phenylephrine from 81 +/- 4 to
      132 +/- 11 mm Hg (P = 0.003). No changes in FAP were seen with epinephrine,
      norepinephrine, and methoxamine. CONCLUSIONS: In the dual perfused, single
      isolated cotyledon, human placental model, exposure of the maternal circulation
      to ephedrine and phenylephrine caused an increase in FAP, whereas exposure to
      norepinephrine, epinephrine, and methoxamine did not. The pharmacodynamic
      mechanisms underlying these differences have yet to be explained. Thus, the
      clinical implications of the findings are as yet unclear.

PMID- 20032026
TI  - A simple approach to the sciatic nerve that does not require geometric
      calculations or multiple landmarks.
AB  - BACKGROUND: Blockade of the sciatic nerve is necessary for complete analgesia of
      the lower extremity using peripheral nerve blocks. We identified the sciatic
      nerve in relation to the ischial tuberosity in fresh cadaver dissections as well
      as in patients to compare sciatic nerve blockade using the conventional approach
      versus our experimental approach. Specifically, we tested the hypothesis that in
      patients in the prone position, our novel approach (changing the point of needle
      insertion to 3 cm lateral from the ischial tuberosity) requires fewer needle
      passes and less time. METHODS: The location of the sciatic nerve in relation to
      the ischial tuberosity was identified in 20 cadavers; this information was used
      to devise an alternative approach to the sciatic nerve. In a randomized,
      controlled, crossover patient study, we compared a prone subgluteal approach
      (conventional approach, n = 19) with an experimental approach with the insertion
      point 3 cm lateral to the midpoint of ischial tuberosity with patients in prone
      position (n = 20). We recorded the number of passes and the time taken to obtain
      an initial sciatic nerve twitch at a current of 1.5 mA and a twitch at <0.5 mA.
      RESULTS: The sciatic nerve averaged 2.8 +/- 0.4 cm from the midpoint of ischial
      tuberosity in cadavers in prone position. When needles were inserted from surface
      landmarks, those inserted through the experimental insertion point consistently
      transected the sciatic nerve. In contrast, needles inserted through the
      conventional approach were 2.27 +/- 0.47 cm lateral to the sciatic nerve.
      Clinically, our experimental approach required fewer passes to obtain a sciatic
      nerve twitch than the conventional approach. We were unable to obtain a twitch in
      55% of patients with the conventional approach and converted them to the
      experimental approach. In patients originally assigned to the experimental
      approach and those switched to the experimental approach after failure with the
      conventional approach, we obtained the first sciatic nerve twitch in 1 pass in
      45% of the patients and in 3 passes in 85%. CONCLUSIONS: We describe a landmark
      that is more effective for identifying the location of the sciatic nerve than
      that used for the prone subgluteal approach.

PMID- 20032028
TI  - Cor triatriatum dexter: a rare cause of neonatal cyanosis.

PMID- 20032027
TI  - Transesophageal echocardiography for tricuspid aortic valve repair.

PMID- 20032029
TI  - Women at the helm in academia and health in the Asia-Pacific region.

PMID- 20032030
TI  - Review paper: epidemiology of traumatic spinal cord injury: comparisons between
      developed and developing countries.
AB  - A review of global epidemiological studies of traumatic spinal cord injury (TSCI)
      within 2 decades was undertaken to compare the incidence, mortality rate,
      patients' age, gender, causes, and severity of injury between developed countries
      and developing countries. The incidence rates varied greatly, and there was also
      a 2-fold difference between the highest mortality rate in developing countries
      and that in developed countries. Male sex and age from 30 to 50 years are strong
      risk factors in both these groups. Traffic accidents are the leading cause of
      injury in developed countries, whereas falls are the leading cause in developing
      countries. To clarify regional differences, future studies should contain long
      term data about TSCI characteristics in a region-based population.

PMID- 20032031
TI  - Island health: hope and challenges for public health.
AB  - The Asia-Pacific region is a region of small islands, perhaps 100 000 of them.
      The health, communication, and development problems of islands present difficult
      challenges for the delivery of health care. The discussions at the Okinawa
      Symposium centred on how health can be provided to all in the region, not only
      those in metropolitan areas, but also the poor in rural areas and those on living
      on far-flung island archipelagos. It is important to apply principles of "public
      health" and "primary health care" so that all island residents may have a
      reasonable expectation of health care. Schools of public health have a special
      responsibility to educate those who are responsible for the delivery and
      management of health care in these remote locations. The development of
      telehealth systems will be important to support health workers in remote
      locations and to deliver continuing education programs.

PMID- 20032032
TI  - Public health responses to climate change health impacts in Indonesia.
AB  - Although climate change is a global concern, there are particular considerations
      for Indonesia as an archipelagic nation. These include the vulnerability of
      people living in small islands and coastal areas to rising sea levels; the
      expansion of the important mosquito-borne diseases, particularly malaria and
      dengue, into areas that lack of immunity; and the increase in water-borne
      diseases and malnutrition. This article proposes a set of public health responses
      to climate change health impacts in Indonesia. Some important principles and
      practices in public health are highlighted, to develop effective public health
      approaches to climate change in Indonesia.

PMID- 20032033
TI  - Income-related health inequalities in Korea.
AB  - Data from the 2001 Korean National Health and Nutrition Examination Survey and
      the ill health concentration index (CI) were used to examine income-related
      health inequalities among Koreans. Participants (>19 years old) were requested to
      provide information regarding monthly household income, expenditures, subjective
      living conditions, and health status. Ill health was determined both subjectively
      through self-rated health (SRH) scores and objectively through the number of
      diseases (ND). At the individual level, the CIs for SRH and ND were -0.147 and 
      0.093, respectively; age-gender adjusted CIs were -0.065 and -0.071,
      respectively. These values remained unchanged when estimating CI for grouped
      data. These results indicate that ill health was more pronounced among lower
      income groups in Korea. However, avoidable health inequality in Korea was smaller
      than in the United Kingdom and the United States, larger than in Sweden, Eastern
      Germany, Finland, and Western Germany, and roughly equal to the Netherlands,
      Spain, and Switzerland.

PMID- 20032034
TI  - The role of health insurance in improving health services use by Thais and ethnic
      minority migrants.
AB  - In Thailand, a universal coverage health care scheme for Thai citizens and a
      foreign worker health insurance program for registered foreign workers have been
      implemented since 2001. This study uses the 2000-2004 panel data of the
      Kanchanaburi Demographic Surveillance System to explore the role of health
      insurance in influencing the use of health care for Thai, Thai ethnic minority,
      and ethnic minority migrants from 2000 to 2004. The results show that health
      insurance plays a major role in improving the use of health care for ethnic
      groups, especially for Thai ethnic minorities. However, a gap still existed in
      2004 between health insurance and health care use by ethnic minority migrants and
      by Thais. The results suggest that improving health insurance status for ethnic
      minority migrants should be encouraged to reduce the ethnic gap in the use of
      health care.

PMID- 20032035
TI  - Socioeconomic and demographic factors associated with health care choices in
      Taiwan.
AB  - By using the data from the 2001 National Health Interview Survey and the National
      Heath Insurance database in Taiwan, this study aims at investigating the
      socioeconomic and demographic factors associated with different health care
      choices. This study incorporated hierarchical cluster analysis into multiple
      correspondent analysis to determine 5 attribute clusters of socioeconomic and
      demographic factors associated with different health care choices. This study
      found that older women with higher education levels were more likely to choose
      multiple sources of health care and that low- to middle-income people were more
      likely to use over-the-counter medications in pharmacies. In addition, people's
      self-reported health care choices were inconsistent with their observed health
      care seeking behavior. The health policy authority may need to provide more
      health promotion education programs, especially for older women with higher
      educational levels, and funding incentives for quality of care provided rather
      than relying solely on reimbursements for episodic care.

PMID- 20032036
TI  - Determinants of infant and child mortality in periurban areas of Kolkata city,
      India.
AB  - Recent Indian studies indicate stagnation in decline of child mortality, though
      various health care interventions were introduced during the last 2 decades. This
      study examined the rates of infant and child mortality and associated demographic
      and socioeconomic factors in 2 socioeconomically vulnerable populations,
      comprising 195 Munda and 334 Poundrakshatriya women having similar access to
      health care facilities in a periurban region of Kolkata city. Higher infant
      mortality rate (IMR) was noted in the older and younger Munda women, in contrast
      to lower IMR in younger Pod women. Child mortality rate was lower in younger
      women in both the ethnic groups. Stagnation in IMR in younger Munda women
      indicates poor delivery practices whereas lower rate among the Pod reflects
      better adoption of safe delivery practices. Differential association of factors
      with infant and child deaths in the 2 populations indicate that a better
      understanding of determinants in culturally heterogeneous populations at the
      community or household level is needed to develop more effective strategies for
      child survival and development.

PMID- 20032037
TI  - Public awareness of risk factors for cancer and its determinants in an Iranian
      population.
AB  - Cancer is increasingly being seen as a disease that is preventable and
      manageable. Knowledge often does constitute one element in the behavior change
      process. In addition, to promote the cancer prevention programs, data on level of
      knowledge among the target population are needed. The present research (as the
      first) aimed at providing information on level and correlates of awareness of
      cancer risk factors among the general public in Iran. The level of knowledge
      about 12 cancer risk factors (as a section of a multipart questionnaire) was
      assessed in a representative sample of 2500 adults (aged >18 years) in Tehran,
      Iran. The data were analyzed using latent class regression with the R statistical
      package. A small proportion of the respondents (12.2%) had high knowledge level
      and most of them had mixed (56.9%) and low level of awareness (30.9%). The most
      important determinants of knowledge level included level of education, gender,
      and family history. The results provided valuable clues and guidelines toward the
      formulation of relevant cancer prevention strategies, especially within the scope
      of health education. The applied statistical model presented a new descriptive
      and analytical perspective to evaluate the level of knowledge about the cancer
      risk factors and its determinants.

PMID- 20032038
TI  - Promoting organ donation through an entertainment-education TV program in Korea:
      Open Your Eyes.
AB  - The purpose of this study is to investigate the effects of the characteristics of
      the program, Open Your Eyes, an entertainment-education TV program in Korea, on
      parasocial interaction and behavioral intention for organ donation. The results
      indicated that affective evaluation positively affected parasocial interaction
      with the program but cognitive evaluation negatively affected involvement with
      beneficiaries in the program. Also, it was found that cognitive evaluation of
      Open Your Eyes had a significant positive effect on behavioral intention. In
      addition, a significant positive effect of program engagement on the behavioral
      intention was found. Thus, the results indicate that individuals who feel program
      engagement of Open Your Eyes will be more likely to proceed with organ donation.
      However, no direct effect of involvement with the beneficiary and program hosts
      was found.

PMID- 20032039
TI  - Support for and reported compliance among smokers with smoke-free policies in air
      conditioned hospitality venues in Malaysia and Thailand: findings from the
      International Tobacco Control Southeast Asia Survey.
AB  - This study examined support for and reported compliance with smoke-free policy in
      air-conditioned restaurants and other similar places among adult smokers in
      Malaysia and Thailand. Baseline data (early 2005) from the International Tobacco
      Control Southeast Asia Survey (ITC-SEA), conducted face-to-face in Malaysia and
      Thailand (n = 4005), were used. Among those attending venues, reported total
      smoking bans in indoor air-conditioned places such as restaurants, coffee shops,
      and karaoke lounges were 40% and 57% in Malaysia and Thailand, respectively.
      Support for a total ban in air-conditioned venues was high and similar for both
      countries (82% Malaysian and 90% Thai smokers who believed there was a total
      ban), but self-reported compliance with bans in such venues was significantly
      higher in Thailand than in Malaysia (95% vs 51%, P < .001). As expected,
      reporting a ban in air-conditioned venues was associated with a greater support
      for a ban in such venues in both countries.

PMID- 20032040
TI  - Prevalence and determinants of malnutrition among reproductive aged women of
      rural Bangladesh.
AB  - Malnutrition among the rural Bangladeshi women of reproductive age is still very
      high. This high prevalence attributes to a range of adverse health consequences
      on the women and their offspring. A total of 2341 women aged between 20 and 45
      years residing in the study area were interviewed in this cross-sectional study.
      Information on socioeconomic variables, nutritional status, and pregnancy-related
      history was obtained using interviewer administered questionnaire. A total of 34%
      of the reproductive aged rural women suffer from malnutrition. A multivariate
      analysis shows association between malnutrition and monthly household income,
      history of taking oral contraceptive, current pregnancy status, and history of
      breastfeeding. The final regression model shows a statistically significant
      decreasing trend in malnutrition status with increasing income (P for trend
      <.001). The economic and health consequences of malnutrition in this group of
      women are enormous. National nutritional program should target this women group
      for any intervention with a special priority.

PMID- 20032041
TI  - Sexual and reproductive health knowledge among female college students in Wuhan,
      China.
AB  - The purpose of this study was to explore demographic correlates of sexual and
      reproductive health knowledge among Chinese female college students. A total of
      4769 participants were surveyed about sexual and reproductive health knowledge
      and related sociodemographic factors, using random cluster sampling between 2005
      and 2006, in 16 colleges and universities in Wuhan, China. To evaluate knowledge,
      the scores of 60 questions on reproduction, contraception, and sexually
      transmitted infections were combined for a possible score of 100. The average
      score on the knowledge scale was 42.6 +/- 13.0 (1.1 to 79.7). Knowledge scores
      were statistically significant (P < 0.01) between different sociodemographic
      factors using chi(2) test. Multilinear stepwise regression showed that 11 of 16
      factors, including age, grade, major, menarche age, family residence, being the
      only child, and mother's occupation were significantly related to knowledge.
      Female college students lack knowledge of sexual and reproductive health, and
      their knowledge was influenced by numerous sociodemographic factors.

PMID- 20032042
TI  - Anxiety prevalence and affecting factors among university students.
AB  - This study provides insight into the prevalence and correlates of anxiety among
      university students in Bursa, Turkey. A total of 4850 students participated in
      the study. Students completed Spielberger's State-Trait Anxiety Inventory, as
      well as a questionnaire designed to determine risk factors of anxiety. About
      29.6% and 36.7% of the students in the study reported state and trait anxiety
      scores of more than 45 points, respectively. Controlling for gender and family
      socioeconomic status, the following characteristics predict both state and trait
      anxiety: the status of family relationships, difficulty understanding lectures,
      difficulty adapting to university life, having to solve problems independently, a
      vision of self-sufficiency in problem solving, negative life experience, and
      satisfaction with their department of study. The following factors are predictive
      of only state anxiety: boarding conditions, having a chronic disease, and exam
      periods. The risk factors for trait anxiety scores include the following: anxiety
      about the future, preparation for work life, class of study, private
      relationships, and attitude of the family toward their child. Families, secondary
      education institutions, and universities should cooperate to eliminate risk
      factors for anxiety among university students.

PMID- 20032043
TI  - Seasonal variation of blood pressure in normotensive females aged 18 to 40 years
      in an urban slum of Delhi, India.
AB  - Season is one of the factors affecting blood pressure. The objectives of this
      study are to quantify the magnitude of seasonal changes in blood pressure among
      normotensive women aged 18 to 40 years and to find out the association of blood
      pressure variation between winter and summer with body mass index, temperature,
      humidity, day length, and salt intake. The study was carried out on 132 women,
      included 4 home visits during the seasons of spring, summer, autumn, and winter.
      Mean increase in systolic blood pressure (SBP)/diastolic blood pressure (DBP) in
      winter was 11.07/6.79 mm Hg during summer (P < .001). No significant relationship
      in blood pressure variation with change in environmental variables was observed.
      Mean increase in SBP/DBP in winter was more among underweight than individuals
      who were normal/overweight/obese (P < .05). There was significant increase in
      SBP/DBP during winter compared with summer. This seasonal factor should be
      considered while evaluating individual blood pressure and comparing community
      studies.

PMID- 20032044
TI  - Abortion for fetal abnormalities in India: need for critical review.

PMID- 20032046
TI  - Siglec-7 mediates nonapoptotic cell death independently of its immunoreceptor
      tyrosine-based inhibitory motifs in monocytic cell line U937.
AB  - Siglec-7, a sialic acid binding immunoglobulin-like lectin, predominantly
      transduces inhibitory signals through cytosolic immunoreceptor tyrosine-based
      inhibitory motifs (ITIMs). Here, we report that clustering of Siglec-7 with a
      specific F(ab')(2) elicited cell death. Interestingly, a truncated Siglec-7
      lacking the cytosolic ITIM domain still induced the cell death, suggesting that
      the ITIMs are not essential for the death signaling. Further analyses of the
      death signaling revealed that an oxygen radical scavenger, N-acetyl cysteine,
      completely inhibited the cell death, whereas a pancaspase inhibitor did not. In
      addition, caspase-3 activation, DNA ladder formation, and nuclear condensation
      were not detected during the death process, suggesting that the cell death is
      nonapoptotic. To identify the critical region for the death signaling, we
      prepared a series of shuffling chimeras between Siglec-7 and Siglec-9, the latter
      of which did not transduce a death signal. The critical region was mapped to the
      middle of the membrane-proximal C2-set domain, which contained only six amino
      acid differences between Siglec-7 and Siglec-9. Point mutation analyses of each
      of these six amino acids revealed that four of the six amino acids were critical
      for the death signal. A computer-assisted 3D modeling revealed that these four
      amino acids were proximally located on the surface of the C2-set domain. In
      conclusion, Siglec-7 induces nonapoptotic cell death, the signal for which is
      transduced by an extracellular C2-set domain.

PMID- 20032047
TI  - The follistatin-288 isoform alone is sufficient for survival but not for normal
      fertility in mice.
AB  - Follistatin (FST) is a natural antagonist of activin and related TGFbeta
      superfamily ligands that exists as three protein isoforms differing in length at
      the C terminus. The longest FST315 isoform is found in the circulation, whereas
      the shortest FST288 isoform is typically found in or on cells and tissues, and
      the intermediate FST303 isoform is found in gonads. We recently demonstrated that
      the FST isoforms have distinct biological actions in vitro that, taken together
      with the differential distribution, suggests they may also have different roles
      in vivo. To explore the specific role of individual FST isoforms, we created a
      single-isoform FST288-only mouse. In contrast to the neonatal death of FST global
      knockout mice, FST288-only mice survive to adulthood. Although they appear
      normal, FST288-only mice have fertility defects including reduced litter size and
      frequency. Follicles were counted in ovaries from 8.5- to 400-d-old females.
      Significantly fewer morphologically healthy antral follicles were found in 100-
      to 250-d FST288-only ovaries, but there were significantly more secondary,
      primary, and primordial follicles detected at d 8.5 in FST288-only ovaries.
      However, depletion of this primordial follicle pool is more rapid in FST288-only
      females resulting in a deficit by 250 d of age and early cessation of
      reproduction. Superovulated FST288-only females have fewer ovulated eggs and
      embryos. These results indicate that the FST isoforms have different activities
      in vivo, that the FST288-only isoform is sufficient for development, and that
      loss of FST303 and FST315 isoforms results in fertility defects that resemble
      activin hyperactivity and premature ovarian failure.

PMID- 20032048
TI  - Minireview: the play of proteins on the parathyroid hormone messenger ribonucleic
      Acid regulates its expression.
AB  - PTH regulates serum calcium and phosphate levels and bone strength. The
      parathyroid is unique in that the trigger for PTH secretion is a low
      extracellular calcium rather than high calcium as for other hormones. The
      parathyroid senses small changes in serum calcium through the seven-trans
      membrane G protein-coupled calcium receptor to alter PTH secretion. PTH then acts
      on bone and kidney to correct serum calcium. Parathyroid cells have few secretory
      granules as compared with other endocrine cells, and therefore PTH production is
      regulated largely at the levels of PTH gene expression and parathyroid cell
      proliferation. The regulation of PTH gene expression by changes in calcium and
      phosphate and in chronic kidney failure is posttranscriptional involving the
      binding of trans-acting proteins to a defined cis element in the PTH mRNA 3'
      untranslated region. These protein-PTH mRNA interactions are orchestrated by the
      peptidyl-prolyl isomerase Pin1. This review discusses the mechanisms of
      regulation of PTH mRNA stability determining serum PTH levels and mineral
      metabolism.

PMID- 20032049
TI  - Minireview: posttranscriptional regulation of the insulin and insulin-like growth
      factor systems.
AB  - Insulin and IGFs share structural similarities and regulate metabolic processes
      including glucose homeostasis. Acute alterations in glucose levels trigger rapid
      changes in insulin concentration and insulin signaling. These processes are
      tightly regulated by posttranscriptional mechanisms that alter the stability and
      translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose
      homeostasis is also modulated by IGFs and IGF receptors, whose expression is
      likewise subject to changes in the stability and translation of the encoding
      mRNAs. The control of mRNA half-life and translation is governed by RNA-binding
      proteins and microRNAs that interact with target transcripts at the 3' and 5'
      untranslated regions. In this review, we describe the RNA-binding proteins and
      microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We
      discuss how these mRNA-binding factors help to elicit timely, versatile, and
      tissue-specific changes in insulin and IGF function, thereby effecting critical
      control of energy metabolism.

PMID- 20032050
TI  - Corticotropin-releasing hormone receptor-1 in cerebral microvessels changes
      during development and influences urocortin transport across the blood-brain
      barrier.
AB  - In this study we tested the hypothesis that receptor-mediated transport of
      urocortin across the blood-brain barrier (BBB) undergoes developmental changes.
      Urocortin is a peptide produced by both selective brain regions and peripheral
      organs, and it is involved in feeding, memory, mood, cardiovascular functions,
      and immune regulation. In BBB studies with multiple-time regression analysis, we
      found that neonatal mice had a significant influx of (125)I-urocortin. By
      contrast, adult mice did not transport urocortin across the BBB. Quantitative RT
      PCR showed that corticotropin-releasing hormone receptor (CRHR)-1 was
      developmentally regulated in enriched cerebral microvessels as well as
      hypothalamus, being significantly higher in neonatal than adult mice. This change
      was less dramatic in agouti viable yellow mice, a strain that develops adult
      onset obesity. The level of expression of CRHR1 mRNA was 33-fold higher in the
      microvessels than in hypothalamic homogenates. The mRNA for CRHR2 was less
      abundant in both regions and less prone to changes with development or the agouti
      viable yellow mutation. Supported by previous findings of receptor-mediated
      endocytosis of urocortin, these results suggest that permeation of urocortin
      across the BBB is dependent on the level of CRHR1 expression in cerebral
      microvessels. These novel findings of differential regulation of CRH receptor
      subtypes help elucidate developmental processes in the brain, particularly for
      the urocortin system.

PMID- 20032051
TI  - The thyrotropin-releasing hormone gene is regulated by thyroid hormone at the
      level of transcription in vivo.
AB  - The expression of the TRH gene in the paraventricular nucleus (PVH) of the
      hypothalamus is required for the normal production of thyroid hormone (TH) in
      rodents and humans. In addition, the regulation of TRH mRNA expression by TH,
      specifically in the PVH, ensures tight control of the set point of the
      hypothalamic-pituitary-thyroid axis. Although many studies have assumed that the
      regulation of TRH expression by TH is at the level of transcription, there is
      little data available to demonstrate this. We used two in vivo model systems to
      show this. In the first model system, we developed an in situ hybridization (ISH)
      assay directed against TRH heteronuclear RNA to measure TRH transcription
      directly in vivo. We show that in the euthyroid state, TRH transcription is
      present both in the PVH and anterior/lateral hypothalamus. In the hypothyroid
      state, transcription is activated in the PVH only and can be shut off within 5 h
      by TH. In the second model system, we employed transgenic mice that express the
      Cre recombinase under the control of the genomic region containing the TRH gene.
      Remarkably, TH regulates Cre expression in these mice in the PVH only. Taken
      together, these data affirm that TH regulates TRH at the level of transcription
      in the PVH only and that genomic elements surrounding the TRH gene mediate its
      regulation by T(3). Thus, it should be possible to identify the elements within
      the TRH locus that mediate its regulation by T(3) using in vivo approaches.

PMID- 20032052
TI  - Prolactin exerts a prosurvival effect on human spermatozoa via mechanisms that
      involve the stimulation of Akt phosphorylation and suppression of caspase
      activation and capacitation.
AB  - The purpose of this study was to examine the impact of prolactin (PRL) on human
      sperm function, in light of a recent proteomic analysis indicating that these
      cells express the PRL receptor (PRLR). Immunocytochemical analyses confirmed the
      presence of PRLR in human spermatozoa and localized this receptor to the
      postacrosomal region of the sperm head as well as the neck, midpiece, and
      principal piece of the sperm tail. Nested PCR analysis indicated that these cells
      possess four splice variants of the PRLR: the long form and three short isoforms,
      one of which is reported for the first time. A combination of Western blot
      analyses and immunocytochemistry demonstrated that PRL inhibited sperm
      capacitation in a dose-dependent manner, suppressing SRC kinase activation and
      phosphotyrosine expression, two hallmarks of this process. The suppression of
      sperm capacitation was accompanied by a powerful prosurvival effect, supporting
      the prolonged motility of these cells and preventing the formation of spontaneous
      DNA strand breaks via mechanisms that involved the concomitant suppression of
      caspase activation. Western blot analyses indicated that the prosurvival effect
      of PRL on human spermatozoa involved the stimulation of Akt phosphorylation,
      whereas inhibitors of phosphatidylinositol-3-OH kinase and Akt negated this
      effect, as did the direct induction of sperm capacitation with cAMP analogues. We
      conclude that PRL is a prosurvival factor for human spermatozoa that prevents
      these cells from defaulting to an intrinsic apoptotic pathway associated with
      cell senescence. These findings have implications for preservation of sperm
      integrity in vivo and in vitro.

PMID- 20032053
TI  - Inhibitor of differentiation (Id) genes are expressed in the steroidogenic cells
      of the ovine ovary and are differentially regulated by members of the
      transforming growth factor-beta family.
AB  - Inhibitor of differentiation (Id) proteins act during embryogenesis and
      development to repress gene transcription required for lineage commitment, while
      promoting cell growth. Growth factors belonging to the TGFbeta superfamily of
      signaling molecules, notably the bone morphogenetic proteins (BMPs) and activin,
      can regulate Id expression in these tissues. Id expression and function in adult
      physiology is less well determined, and we hypothesized a role for Id proteins in
      the adult mammalian ovary. Immunohistochemistry for Id1, Id2, Id3, and Id4 in the
      sheep ovary revealed consistent expression in granulosa and thecal cells of
      ovarian follicles throughout development. In atretic follicles, Id proteins were
      selectively down-regulated in thecal cells (P < 0.0001). Additionally, Id1 was
      universally up-regulated in the cumulus cells adjacent to the oocyte.
      Immunohistochemistry for phospho (p)-smad 1/5/8 signaling components (stimulated
      by BMPs) showed a punctate pattern of expression whereas p-smad 2/3 (stimulated
      by activin) was ubiquitously expressed in follicles. Neither pathway, however,
      displayed differential staining in line with Id1 cumulus-specific expression,
      suggesting a more complex relationship between Id1 expression and TGFbeta
      signaling in these cells. Nevertheless, in vitro, stimulation of ovine granulosa
      cells with BMP6 or activin A led to a respective increase and decrease in Id1 (P
      < 0.0001), Id2 (P < 0.0001), Id3 (P < 0.0001), and Id4 (P < 0.05) transcripts,
      and Id1 gene expression was further manipulated by the oocyte-secreted factors
      BMP15 and growth differentiation factor 9 (P < 0.001). These data confirm that
      TGFbeta signaling can regulate Id gene expression in the sheep ovarian follicle
      and suggest a functional role for the Id family in the mammalian ovary.

PMID- 20032054
TI  - Regular pacemaker activity characterizes gonadotropin-releasing hormone 2 neurons
      recorded from green fluorescent protein-transgenic medaka.
AB  - GnRH2 is a molecule conserved from fish to humans, suggesting its important
      functions. However, recent studies have shown that GnRH2 neurons project widely
      in the brain but not to the pituitary, which suggests their functions other than
      stimulation of gonadotropin secretion. In contrast to the wealth of knowledge in
      GnRH1 and GnRH3 neuronal systems, the GnRH2 neuronal system remains to be
      studied, and there has been no single cell approach so far, partly because of the
      lack of GnRH2 system in rodents. Here, we generated GnRH2-green fluorescent
      protein (GFP) transgenic medaka for the first single cell electrophysiological
      recording from GnRH2 neurons in vertebrates. Whole-cell and on-cell patch clamp
      analyses revealed their regular pacemaker activities that are intrinsic to the
      GnRH2 neurons. Pacemaker activities of GnRH2 neurons were not peculiar to medaka
      because dwarf gourami GnRH2 neurons also showed similar pacemaker activities. By
      comparing with spontaneous action currents from GFP-expressing GnRH1 and GnRH3
      neurons in the adult transgenic medaka, which were already in our hands, we have
      demonstrated that GnRH2 neurons show pacemaker activity similar to
      nonhypophysiotropic GnRH3 neurons but not to hypophysiotropic GnRH1 neurons.
      Thus, by taking advantage of medaka brain, which has all three GnRH neuronal
      systems with different axonal projection patterns and thus different functions,
      we have gained insights into the close relationship between the pattern of
      spontaneous electrical activity and the functions of the three. Moreover, the
      three types of GnRH-GFP transgenic medaka will provide useful models for studying
      multifunctional GnRH systems in future.

PMID- 20032055
TI  - Antidiabetic properties of zinc-alpha2-glycoprotein in ob/ob mice.
AB  - Zinc-alpha(2)-glycoprotein (ZAG) is an adipokine associated with fat loss in
      cancer cachexia. The purpose of this study was to evaluate the ability of
      recombinant human ZAG to attenuate type 2 diabetes in the ob/ob mouse model. ZAG
      (50 microg daily, iv) induced a progressive loss of body weight (3.5 g in 5 d),
      without an effect on food or water intake but with a 0.4 C rise in body
      temperature, suggesting an increased energy expenditure. Despite an increased
      plasma glycerol, indicative of increased lipolysis, levels of glucose,
      triglycerides, and nonesterified fatty acids were decreased by 17, 25, and 62%,
      respectively, due to an increased use of both glucose and lipids by muscle and
      brown adipose tissue. The weight of the latter increased 2-fold, and there was
      increased expression of uncoupling proteins-1 and -3. Plasma insulin levels were
      reduced by 36%, whereas pancreatic insulin was increased 4-fold, and there was a
      53% decrease in the total area under the glucose curve in the glucose tolerance
      test and reduced insulin requirement. There was an increase in skeletal muscle
      mass due to an increase in protein synthesis and a decrease in protein
      degradation. These results suggest that ZAG may potentially be effective in the
      treatment of type 2 diabetes.

PMID- 20032056
TI  - Insulin-like growth factor 2 and the insulin receptor, but not insulin, regulate
      fetal hepatic glycogen synthesis.
AB  - Whether insulin or IGFs regulate glycogen synthesis in the fetal liver remains to
      be determined. In this study, we used several knockout mouse strains, including
      those lacking Pdx-1 (pancreatic duodenal homeobox-1), Insr (insulin receptor),
      and Igf2 (IGF-II) to determine the role of these genes in the regulation of fetal
      hepatic glycogen synthesis. Our data show that insulin deficiency does not alter
      hepatic glycogen stores, whereas Insr and Igf2 deficiency do. We found that both
      insulin receptor isoforms (IR-A and IR-B) are present in the fetal liver, and
      their expression is gestationally regulated. IR-B is highly expressed in the
      fetal liver; nonetheless, the percentage of hepatic IR-A isoform, which binds
      Igf2, was significantly higher in the fetus than the adult. In vitro experiments
      demonstrate that Igf2 increases phosphorylation of hepatic Insr, insulin receptor
      substrate-2, and Akt proteins and also the activity of glycogen synthase. Igf2
      ultimately increased glycogen synthesis in fetal hepatocytes. This increase could
      be blocked by the phosphoinositide 3-kinase inhibitor LY294008. Taken together,
      we propose Igf2 as a major regulator of fetal hepatic glycogen metabolism, the
      insulin receptor as its target receptor, and phosphoinositide 3-kinase as the
      signaling pathway leading to glycogen formation in the fetal liver.

PMID- 20032057
TI  - Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure,
      expression, and functions.
AB  - Maternally expressed gene 3 (MEG3) is an imprinted gene highly expressed in the
      human pituitary. However, MEG3 expression is lost in human gonadotroph-derived
      pituitary adenomas and most human tumor cell lines. Expression of MEG3 in tumor
      cells results in growth suppression, p53 protein increase, and activation of p53
      downstream targets. The MEG3 gene encodes a noncoding RNA of approximately 1700
      nucleotides. There are 12 different MEG3 gene transcripts, generated by
      alternative splicing. They contain the common exons 1-3 and exons 8-10, but each
      uses one or more exons 4-7 in a different combination in the middle. MEG3 isoform
      expression patterns are tissue and cell type specific. Functionally, each isoform
      stimulates p53-mediated transactivation and suppresses tumor cell growth. We
      analyzed the secondary RNA folding structure of each MEG3 isoform, using the
      computer program mfold. All MEG3 RNA isoforms contain three distinct secondary
      folding motifs M1, M2, and M3. Deletion analysis showed that motifs M2 and M3 are
      important for p53 activation. Furthermore, a hybrid MEG3 RNA, containing a piece
      of artificially synthesized sequence different from the wild type but folding
      into a similar secondary structure, retained the functions of both p53 activation
      and growth suppression. These results support the hypothesis that a proper
      folding structure of the MEG3 RNA molecule is critical for its biological
      functions. This study establishes for the first time the structure-function
      relationship of a large noncoding RNA and provides a first look into the
      molecular mechanisms of the biological functions of a large noncoding RNA.

PMID- 20032058
TI  - REDD1 is a major target of testosterone action in preventing dexamethasone
      induced muscle loss.
AB  - Glucocorticoids are a well-recognized and common cause of muscle atrophy that can
      be prevented by testosterone. However, the molecular mechanisms underlying such
      protection have not been described. Thus, the global effects of testosterone on
      dexamethasone-induced changes in gene expression were evaluated in rat
      gastrocnemius muscle using DNA microarrays. Gene expression was analyzed after 7
      d administration of dexamethasone, dexamethasone plus testosterone, or vehicle.
      Dexamethasone changed expression of 876 probe sets by at least 2-fold. Among
      these, 474 probe sets were changed by at least 2-fold in the opposite direction
      in the dexamethasone plus testosterone group (genes in opposition). Major
      biological themes represented by genes in opposition included IGF-I signaling,
      myogenesis and muscle development, and cell cycle progression. Testosterone
      completely prevented the 22-fold increase in expression of the mammalian target
      of rapamycin (mTOR) inhibitor regulated in development and DNA damage responses 1
      (REDD1), and attenuated dexamethasone induced increased expression of eIF4E
      binding protein 1, Forkhead box O1, and the p85 regulatory subunit of the IGF-I
      receptor but prevented decreased expression of IRS-1. Testosterone attenuated
      increases in REDD1 protein in skeletal muscle and L6 myoblasts and prevented
      dephosphorylation of p70S6 kinase at the mTOR-dependent site Thr389 in L6
      myoblast cells. Effects of testosterone on REDD1 mRNA levels occurred within 1 h,
      required the androgen receptor, were blocked by bicalutamide, and were due to
      inhibition of transcriptional activation of REDD1 by dexamethasone. These data
      suggest that testosterone blocks dexamethasone-induced changes in expression of
      REDD1 and other genes that collectively would otherwise down-regulate mTOR
      activity and hence also down-regulate protein synthesis.

PMID- 20032059
TI  - Thyroid hormone-induced cardiac mechano growth factor expression depends on
      beating activity.
AB  - The mechano growth factor (MGF), a splice variant of the IGF-I gene, was first
      discovered in mechanically overloaded skeletal muscle and was shown to play an
      important role in proliferation of muscle stem cells. Since then, the presence
      and effects of MGF have been demonstrated in other tissues. MGF has been shown to
      act neuroprotectively during brain ischemia, and pretreatment with MGF before
      myocardial infarction improves cardiac function. Because MGF plays a permissive
      role in exercise-induced skeletal muscle hypertrophy, we hypothesize that MGF is
      commonly involved in cardiac hypertrophy. To investigate the regulation of MGF
      expression in heart, mice were treated with thyroid hormone (T(3)) for 12 d to
      induce physiological cardiac hypertrophy. MGF mRNA expression was specifically
      increased in midregions of the septum and left ventricular wall. Interestingly,
      MGF expression strongly correlated with the increased or decreased beating
      frequency of hyperthyroid and hypothyroid hearts. To further investigate the
      mechanically dependent induction of MGF, neonatal rat cardiomyocytes were
      isolated and exposed to T(3). Upon T(3) treatment, cardiomyocytes increased both
      contractile activity measured as beats per minute and MGF as well as IGF-IEa mRNA
      expression. Importantly, when cardiomyocytes were contractile arrested by KCl,
      simultaneous exposure to T(3) prevented the up-regulation of MGF, whereas IGF-IEa
      was still induced. These studies demonstrated that MGF but not IGF-IEa expression
      is dependent on beating activity. These findings suggest that MGF is specifically
      stimulated by mechanical loading of the heart to mediate the hypertrophic
      response to thyroid hormone.

PMID- 20032060
TI  - Delivering the code: polyplex carriers for deoxyribonucleic acid and ribonucleic
      acid interference therapies.
AB  - Nucleic acid-based therapies offer great potential for treatment of a variety of
      diseases including cancer by modulating protein expression with DNA or small
      interfering RNA. However, realization of their full therapeutic potential is
      currently limited due to an inability to reach the target site in an active form.
      Identification of delivery barriers such as stability in circulation, resistance
      to degradation and entrapment in subcellular vesicles has led to development of
      sophisticated multifunctional synthetic polymers for forming ionic complexes with
      nucleic acids and also providing performance-enhancing features. The most
      promising designs comprise features to help increase stability in circulation and
      also contain functionality to aid in endosome escape of nucleic acid cargo after
      cellular internalization.

PMID- 20032061
TI  - Testosterone induces redistribution of forkhead box-3a and down-regulation of
      growth and differentiation factor 9 messenger ribonucleic acid expression at
      early stage of mouse folliculogenesis.
AB  - Increasing evidence has shown that excess androgen may be a main cause of
      polycystic ovary syndrome (PCOS). However, the molecular mechanism of androgen
      action on the ovary is unclear. To investigate the possible impacts of androgen
      on early follicular development, neonatal mouse ovaries mainly containing
      primordial follicles were cultured with testosterone. We demonstrated that the
      number of primary follicles was increased after 10 d culture with testosterone
      treatment via phosphatidylinositol 3-kinase/Akt pathway. Androgen induced
      Forkhead box (Foxo)-3a activation, and translocation of Foxo3a protein from
      oocyte nuclei to cytoplasm, which might be a key step for primordial follicle
      activation. Interestingly, testosterone was also capable of down-regulating
      growth and differentiation factor-9 expression via its receptor. In summary, we
      infer that intraovarian excess androgen in PCOS might result in excess early
      follicles by inducing oocyte Foxo3a translocation and follicular arrest by down
      regulating growth and differentiation factor-9 expression.

PMID- 20032062
TI  - Life-span changes of the human brain white matter: diffusion tensor imaging (DTI)
      and volumetry.
AB  - Magnetic resonance imaging volumetry studies report inverted U-patterns with
      increasing white-matter (WM) volume into middle age suggesting protracted WM
      maturation compared with the cortical gray matter. Diffusion tensor imaging (DTI)
      is sensitive to degree and direction of water permeability in biological tissues,
      providing in vivo indices of WM microstructure. The aim of this cross-sectional
      study was to delineate age trajectories of WM volume and DTI indices in 430
      healthy subjects ranging 8-85 years of age. We used automated regional brain
      volume segmentation and tract-based statistics of fractional anisotropy, mean,
      and radial diffusivity as markers of WM integrity. Nonparametric regressions were
      used to fit the age trajectories and to estimate the timing of maximum
      development and deterioration in aging. Although the volumetric data supported
      protracted growth into the sixth decade, DTI indices plateaued early in the
      fourth decade across all tested regions and then declined slowly into late
      adulthood followed by an accelerating decrease in senescence. Tractwise and voxel
      based analyses yielded regional differences in development and aging but did not
      provide ample evidence in support of a simple last-in-first-out hypothesis of
      life-span changes.

PMID- 20032063
TI  - Pharmacological or genetic inactivation of the serotonin transporter improves
      reversal learning in mice.
AB  - Growing evidence supports a major contribution of cortical serotonin (5
      hydroxytryptamine, 5-HT) to the modulation of cognitive flexibility and the
      cognitive inflexibility evident in neuropsychiatric disorders. The precise role
      of 5-HT and the influence of 5-HT gene variation in mediating this process is not
      fully understood. Using a touch screen-based operant system, we assessed reversal
      of a pairwise visual discrimination as an assay for cognitive flexibility.
      Effects of constitutive genetic or pharmacological inactivation of the 5-HT
      transporter (5-HTT) on reversal were examined by testing 5-HTT null mice and
      chronic fluoxetine-treated C57BL/6J mice, respectively. Effects of constitutive
      genetic loss or acute pharmacological depletion of 5-HT were assessed by testing
      Pet-1 null mice and para-chlorophenylalanine (PCPA)-treated C57BL/6J mice,
      respectively. Fluoxetine-treated C57BL/6J mice made fewer errors than controls
      during the early phase of reversal when perseverative behavior is relatively
      high. 5-HTT null mice made fewer errors than controls in completing the reversal
      task. However, reversal in Pet-1 null and PCPA-treated C57BL/6J mice was not
      different from controls. These data further support an important role for 5-HT in
      modulating reversal learning and provide novel evidence that inactivating the 5
      HTT improves this process. These findings could have important implications for
      understanding and treating cognitive inflexibility in neuropsychiatric disease.

PMID- 20032064
TI  - Segregation analysis of a sex ratio distortion locus in congenic mice.
AB  - The congenic HG.CAST-(D17Mit196-D17Mit190) (HQ17(hg/hg)) mouse strain showed a
      significant departure on the expected 50%/50% offspring sex ratio in more than
      2400 progeny (55.7% females). The entire pedigree file included data from 13
      nonoverlapping purebred generations and an F(2) cross with the C57BL/6J inbred
      strain. Offspring sex ratio data were analyzed on the basis of 40 purebred
      HQ17(hg)(/hg) sires and 29 F(1) HQ17(hg)(/hg) x B6 sires under a Bayesian
      Binomial segregation model accounting for 4 different autosomal inheritance
      models of gene action (i.e., additive, dominance, recessive, and overdominance)
      and X-linked and Y-linked loci. For each model, the segregation effect was
      evaluated as a single regression coefficient for all sires or assuming 2
      independent regression coefficients accounting for offspring sex ratio departures
      in purebred and F(1) sires, respectively. The deviance information criterion
      clearly favored the autosomal dominance model with different regression
      coefficients for the 2 groups of sires. Under this model, the dominance effect
      increased the percentage of female offspring by 4.3% (HQ17(hg)(/hg) purebred
      sires) and 8.2% (F(1) sires) with the highest posterior density regions ranging
      from 0.5% to 10.6% and from 1.3% to 14.4%, respectively. This article provides
      significant evidence of genetic determinism for sex ratio distortion in the
      HQ17(hg)(/hg) strain and develops new analytical tools to perform segregation
      studies on dichotomous traits.

PMID- 20032065
TI  - Management of atrial fibrillation.

PMID- 20032066
TI  - Observers voice concerns about trial of herbal remedy in Cambodian opiate
      addicts.

PMID- 20032067
TI  - Metformin and lactic acidosis. NSAIDs and renin-angiotensin-aldosterone system.

PMID- 20032068
TI  - Metformin and lactic acidosis. Metformin: framed again?

PMID- 20032069
TI  - Time to rethink aspirin in diabetes?

PMID- 20032070
TI  - Ethics in sports medicine. Editorial was wide of the mark.

PMID- 20032072
TI  - Spanish Congress takes the first step towards abortion on demand.

PMID- 20032076
TI  - Hope for Humpty Dumpty: systems biology of cellular signaling.

PMID- 20032077
TI  - The Arabidopsis BET bromodomain factor GTE4 is involved in maintenance of the
      mitotic cell cycle during plant development.
AB  - Bromodomain and Extra Terminal domain (BET) proteins are characterized by the
      presence of two types of domains, the bromodomain and the extra terminal domain.
      They bind to acetylated lysines present on histone tails and control gene
      transcription. They are also well known to play an important role in cell cycle
      regulation. In Arabidopsis (Arabidopsis thaliana), there are 12 BET genes;
      however, only two of them, IMBIBITION INDUCIBLE1 and GENERAL TRANSCRIPTION FACTOR
      GROUP E6 (GTE6), were functionally analyzed. We characterized GTE4 and show that
      gte4 mutant plants have some characteristic features of cell cycle mutants. Their
      size is reduced, and they have jagged leaves and a reduced number of cells in
      most organs. Moreover, cell size is considerably increased in the root, and,
      interestingly, the root quiescent center identity seems to be partially lost.
      Cell cycle analyses revealed that there is a delay in activation of the cell
      cycle during germination and a premature arrest of cell proliferation, with a
      switch from mitosis to endocycling, leading to a statistically significant
      increase in ploidy levels in the differentiated organs of gte4 plants. Our
      results point to a role of GTE4 in cell cycle regulation and specifically in the
      maintenance of the mitotic cell cycle.

PMID- 20032078
TI  - AGRONOMICS1: a new resource for Arabidopsis transcriptome profiling.
AB  - Transcriptome profiling has become a routine tool in biology. For Arabidopsis
      (Arabidopsis thaliana), the Affymetrix ATH1 expression array is most commonly
      used, but it lacks about one-third of all annotated genes present in the
      reference strain. An alternative are tiling arrays, but previous designs have not
      allowed the simultaneous analysis of both strands on a single array. We introduce
      AGRONOMICS1, a new Affymetrix Arabidopsis microarray that contains the complete
      paths of both genome strands, with on average one 25mer probe per 35-bp genome
      sequence window. In addition, the new AGRONOMICS1 array contains all perfect
      match probes from the original ATH1 array, allowing for seamless integration of
      the very large existing ATH1 knowledge base. The AGRONOMICS1 array can be used
      for diverse functional genomics applications such as reliable expression
      profiling of more than 30,000 genes, detection of alternative splicing, and
      chromatin immunoprecipitation coupled to microarrays (ChIP-chip). Here, we
      describe the design of the array and compare its performance with that of the
      ATH1 array. We find results from both microarrays to be of similar quality, but
      AGRONOMICS1 arrays yield robust expression information for many more genes, as
      expected. Analysis of the ATH1 probes on AGRONOMICS1 arrays produces results that
      closely mirror those of ATH1 arrays. Finally, the AGRONOMICS1 array is shown to
      be useful for ChIP-chip experiments. We show that heterochromatic H3K9me2 is
      strongly confined to the gene body of target genes in euchromatic chromosome
      regions, suggesting that spreading of heterochromatin is limited outside of
      pericentromeric regions.

PMID- 20032079
TI  - Expression quantitative trait loci analysis of two genes encoding rubisco
      activase in soybean.
AB  - Rubisco activase (RCA) catalyzes the activation of Rubisco in vivo and plays a
      crucial role in photosynthesis. However, until now, little was known about the
      molecular genetics of RCA in soybean (Glycine max), one of the most important
      legume crops. Here, we cloned and characterized two genes encoding the longer
      alpha -isoform and the shorter beta -isoform of soybean RCA (GmRCA alpha and
      GmRCA beta, respectively). The two corresponding cDNAs are divergent in both the
      translated and 3 ' untranslated regions. Analysis of genomic DNA sequences
      suggested that the corresponding mRNAs are transcripts of two different genes and
      not the products of a single alternatively splicing pre-mRNA. Two additional
      possible alpha -form RCA-encoding genes, GmRCA03 and GmRCA14, and one additional
      beta -form RCA-encoding gene, GmRCA11, were also isolated. To examine the
      function and modulation of RCA genes in soybean, we determined the expression
      levels of GmRCA alpha and GmRCA beta, Rubisco initial activity, photosynthetic
      rate, and seed yield in 184 soybean recombinant inbred lines. Correlation of gene
      expression levels with three other traits indicates that RCA genes could play an
      important role in regulating soybean photosynthetic capacity and seed yield.
      Expression quantitative trait loci mapping revealed four trans-expression
      quantitative trait loci for GmRCA alpha and GmRCA beta. These results could
      provide a new approach for the modulation of RCA genes to improve photosynthetic
      rate and plant growth in soybean and other plants.

PMID- 20032080
TI  - Kinetic and spectral resolution of multiple nonphotochemical quenching components
      in Arabidopsis leaves.
AB  - Using novel specially designed instrumentation, fluorescence emission spectra
      were recorded from Arabidopsis (Arabidopsis thaliana) leaves during the induction
      period of dark to high-light adaptation in order to follow the spectral changes
      associated with the formation of nonphotochemical quenching. In addition to an
      overall decrease of photosystem II fluorescence (quenching) across the entire
      spectrum, high light induced two specific relative changes in the spectra: (1) a
      decrease of the main emission band at 682 nm relative to the far-red (750-760 nm)
      part of the spectrum (Delta F(682)); and (2) an increase at 720 to 730 nm (Delta
      F(720)) relative to 750 to 760 nm. The kinetics of the two relative spectral
      changes and their dependence on various mutants revealed that they do not
      originate from the same process but rather from at least two independent
      processes. The Delta F(720) change is specifically associated with the rapidly
      reversible energy-dependent quenching. Comparison of the wild-type Arabidopsis
      with mutants unable to produce or overexpressing the PsbS subunit of photosystem
      II showed that PsbS was a necessary component for Delta F(720). The spectral
      change Delta F(682) is induced both by energy-dependent quenching and by PsbS
      independent mechanism(s). A third novel quenching process, independent from both
      PsbS and zeaxanthin, is activated by a high turnover rate of photosystem II. Its
      induction and relaxation occur on a time scale of a few minutes. Analysis of the
      spectral inhomogeneity of nonphotochemical quenching allows extraction of
      mechanistically valuable information from the fluorescence induction kinetics
      when registered in a spectrally resolved fashion.

PMID- 20032081
TI  - PPARgamma agonists inhibit angiogenesis by suppressing PKCalpha- and CREB
      mediated COX-2 expression in the human endothelium.
AB  - AIMS: The activation of peroxisome proliferator-activated receptor (PPAR)gamma is
      known to inhibit angiogenesis. As a potential mechanism for this, we aimed at
      examining the effects of PPARgamma agonists on the pro-angiogenic enzyme
      cyclooxygenase (COX)-2 in human endothelium. METHODS AND RESULTS: Cultured
      endothelial cells were pre-incubated with the PPARgamma agonists rosiglitazone
      (RSG) or GW1929 before stimulation with vascular endothelial growth factor (VEGF)
      or phorbol myristate acetate (PMA). RSG and GW1929 attenuated VEGF- and PMA
      stimulated COX-2 activity, as well as protein and mRNA expression. This effect
      was abolished by the PPARgamma antagonists bisphenol A diglycidyl ether and
      GW9662 as well as by PPARgamma small-interfering RNAs (siRNAs). Transient
      transfection experiments revealed that the induction of COX-2 promoter was
      significantly inhibited by RSG through an interference with the cAMP response
      element (CRE) site. COX-2 downregulation after siRNA targeting CRE-binding
      protein (CREB) confirmed the role of CREB in mediating COX-2 transcription.
      Correspondingly, PPARgamma agonists attenuated CREB activation. As both protein
      kinase C (PKC)alpha and beta are involved in VEGF-induced COX-2 expression and
      CREB activation, we investigated which isoform(s) of PKC was affected by RSG. RSG
      only reduced VEGF- and PMA-stimulated PKCalpha membrane translocation.
      CONCLUSION: VEGF induces CREB-mediated COX-2 expression through a PKCalpha
      dependent pathway in human endothelium. The anti-angiogenic effect of PPARgamma
      agonists is due, at least in part, to an interference with the VEGF-stimulated
      PKCalpha-mediated activation of CREB and the related expression of COX-2.

PMID- 20032082
TI  - Sodium channel traffic on the cardiac microtubule highway.

PMID- 20032083
TI  - Nitric oxide reduces SLC29A1 promoter activity and adenosine transport involving
      transcription factor complex hCHOP-C/EBPalpha in human umbilical vein endothelial
      cells from gestational diabetes.
AB  - AIMS: Reduced expression of human equilibrative nucleoside transporter 1 (hENT1)
      results from nitric oxide (NO)-dependent reduced SLC29A1 transcriptional activity
      in human umbilical vein endothelial cells (HUVECs) from gestational diabetes. As
      expression of the transcription factor C/EBP homologous protein 10 (hCHOP, which
      forms heterodimers with C/EBPalpha transcription factor) is activated by NO and
      induced in diabetes mellitus, we hypothesize that hCHOP plays a role in the
      gestational diabetes-reduced hENT1 expression in HUVECs. METHODS AND RESULTS:
      HUVEC primary cultures from 42 normal and 42 gestational diabetic pregnancies
      were used for adenosine uptake assays. Real-time PCR (mRNA quantification),
      western blotting (protein abundance), and luciferase activity (SLC29A1 promoter
      activity) were used. hCHOP-C/EBPalpha activity was assayed by chromatin
      immunoprecipitation. Overlap extension mutagenesis was used to generate a mutated
      hCHOP-C/EBPalpha consensus site at the SLC29A1 promoter, and endothelial NO
      synthase (eNOS) siRNA recombinant adenovirus was used to knock down eNOS. hCHOP
      nuclear protein abundance and binding to DNA were higher in gestational diabetes,
      paralleled by reduced SLC29A1 promoter activity, hENT1 expression, and transport
      activity. These changes were blocked by hCHOP consensus sequence mutation (-1845G
      > T and -1844C > A), eNOS-siRNA-induced knockdown, and N(G)-nitro-L-arginine
      methyl ester (NOS inhibitor), and were mimicked by S-nitroso-N-acetyl-L, D
      penicillamine (NO donor) in cells from normal pregnancies. hCHOP and C/EBPalpha
      overexpression mimicked gestational diabetes effects in cells from normal
      pregnancies, but did not alter SLC29A1 promoter activity or hENT1-adenosine
      transport in cells from gestational diabetes. CONCLUSION: The hCHOP-C/EBPalpha
      complex down-regulates SLC29A1 expression in an NO-dependent manner in HUVECs
      from gestational diabetes.

PMID- 20032084
TI  - Cyclooxygenase-2 preserves flow-mediated remodelling in old obese Zucker rat
      mesenteric arteries.
AB  - AIMS: Resistance arteries have a key role in the control of local blood flow and
      pressure, and chronic increases in blood flow induce endothelium-dependent
      outward hypertrophic remodelling. The incidence of metabolic syndrome increases
      with age, and the combination of these two risk factors impairs endothelium
      integrity, in part through an inflammatory process. We hypothesized that
      cyclooxygenase-2 (COX2) would affect remodelling in 12-month-old obese rats
      compared with young rats. METHODS AND RESULTS: Mesenteric arteries of obese and
      lean Zucker rats were alternatively ligated to generate high flow (HF) in the
      median artery. After 21 days, arteries were isolated for in vitro analysis. After
      21 days, outward hypertrophic remodelling occurred in HF arteries in obese (498
      +/- 20 vs. 443 +/- 18 mum intraluminal diameter in normal flow (NF) arteries, P <
      0.01), but not in lean rats (454 +/- 17 vs. 432 +/- 14, NS; n = 12 per group).
      Endothelium-dependent (acetylcholine)-mediated relaxation (AMR) was lower in
      obese than in lean rats. AMR was reduced by NO-synthase blockade in all groups,
      and eNOS expression was higher in HF than in NF arteries without difference
      between lean and obese rats. Indomethacin further reduced AMR in HF arteries from
      obese rats only. Obesity increased COX2 immunostaining in mesenteric arteries.
      Acute COX2 inhibition (NS398) significantly reduced AMR in HF arteries from obese
      rats only, suggesting production of vasodilator prostanoid(s). In obese rats
      chronically treated with the COX2 inhibitor celecoxib, outward remodelling did
      not occur in HF arteries and AMR was improved without reaching the level found in
      lean rats. CONCLUSION: COX2 preserved in part flow-mediated arterial remodelling
      in old obese rats. Nevertheless, this effect was not sufficient to keep
      endothelium-dependent relaxation to the level obtained in lean rats.

PMID- 20032085
TI  - Cerebral haemodynamics in patients with glutaryl-coenzyme A dehydrogenase
      deficiency.
AB  - In glutaric aciduria type 1, glutaryl-coenzyme A and its derivatives are produced
      from intracerebral lysine and entrapped at high concentrations within the brain,
      where they interfere with energy metabolism. Biochemical toxicity is thought to
      trigger stroke-like striatal degeneration in susceptible children under 2 years
      of age. Here, we explore vascular derangements that might also contribute to
      brain damage. We studied injured and non-injured Amish glutaric aciduria type 1
      patients using magnetic resonance imaging (n = 26), transcranial Doppler
      ultrasound (n = 35) and perfusion computed tomography (n = 6). All glutaric
      aciduria type 1 patients had wide middle cerebral, internal carotid and basilar
      arteries. In non-injured patients, middle cerebral artery velocities were 18-26%
      below control values throughout late infancy and early childhood, whereas brain
      injured children had an early velocity peak (18 months) and low values
      thereafter. Perfusion scans from six patients showed that tissue blood flow did
      not undergo a normal developmental surge. We observed four different perfusion
      patterns. (i) Three children (two non-injured) had low cerebral blood flow,
      prolonged mean transit time, elevated cerebral blood volume and high mean transit
      time/cerebral blood flow and cerebral blood volume/cerebral blood flow ratios.
      This pattern optimizes substrate extraction at any given flow rate but indicates
      low perfusion pressure and limited autoregulatory reserve. (ii) Ten hours after
      the onset of striatal necrosis in an 8-month-old infant, mean transit time and
      cerebral blood volume were low relative to cerebral blood flow, which varied
      markedly from region to region. This pattern indicates disturbed autoregulation,
      regional perfusion pressure gradients, or redistribution of flow from functional
      capillaries to non-exchanging vessels. (iii) In an infant with atrophic putaminal
      lesions, striatal flow was normal but mean transit time and cerebral blood volume
      were low, consistent with perfusion in excess of metabolic demand. (iv) Finally,
      a brain-injured adult with glutaric aciduria type 1 had regional perfusion values
      within the normal range, but the putamina, which normally have the highest
      regional perfusion, had cerebral blood flow values 24% below cortical grey
      matter. Although metabolic toxicity appears central to the pathophysiology of
      striatal necrosis, cerebrovascular changes probably also contribute to the
      process. These changes may be the primary cause of expanded cerebrospinal fluid
      volume in newborns, intracranial and retinal haemorrhages in infants and
      interstitial white matter oedema in children and adults. This pilot study
      suggests important new areas for clinical investigation.

PMID- 20032086
TI  - Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy
      phenotype in mice.
AB  - Spinal muscular atrophy, characterized by selective loss of lower motor neurons,
      is an incurable genetic neurological disease leading to infant mortality. We
      previously showed that primary neural stem cells derived from spinal cord can
      ameliorate the spinal muscular atrophy phenotype in mice, but this primary source
      has limited translational value. Here, we illustrate that pluripotent stem cells
      from embryonic stem cells show the same potential therapeutic effects as those
      derived from spinal cord and offer great promise as an unlimited source of neural
      stem cells for transplantation. We found that embryonic stem cell-derived neural
      stem cells can differentiate into motor neurons in vitro and in vivo. In
      addition, following their intrathecal transplantation into spinal muscular
      atrophy mice, the neural stem cells, like those derived from spinal cord,
      survived and migrated to appropriate areas, ameliorated behavioural endpoints and
      lifespan, and exhibited neuroprotective capability. Neural stem cells obtained
      using a drug-selectable embryonic stem cell line yielded the greatest
      improvements. As with cells originating from primary tissue, the embryonic stem
      cell-derived neural stem cells integrated appropriately into the parenchyma,
      expressing neuron- and motor neuron-specific markers. Our results suggest
      translational potential for the use of pluripotent cells in neural stem cell
      mediated therapies and highlight potential safety improvements and benefits of
      drug selection for neuroepithelial cells.

PMID- 20032092
TI  - Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: a
      study of PSTPIP2, NOD2, and LPIN2 genes.
AB  - OBJECTIVE: The SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and
      osteitis) is a rare disorder that mainly affects bone and skin. Chronic
      multifocal osteitis is the main diagnostic feature. Genetic studies of HLA genes
      have shown no role for these class II antigens, whereas studies of 2 mouse models
      (cmo and Lupo) point to a role of the PSTPIP2 gene. We analyzed the PSTPIP2 gene
      in patients with SAPHO syndrome. METHODS: In a cohort of 38 patients with SAPHO
      we analyzed PSTPIP2 and 2 other candidate genes, NOD2/CARD15 (Crohn's disease
      occurs in about 10% of SAPHO patients), and LPIN2 (clinical similarities of SAPHO
      with Majeed syndrome). RESULTS: Rare variants of the 3 genes observed in patients
      with SAPHO were not specific or were not found more frequently compared to
      controls, suggesting no major pathogenetic role of these genes in the SAPHO
      syndrome. CONCLUSION: We found no association between PSTPIP2, NOD2, and LPIN2
      variants and the SAPHO syndrome.

PMID- 20032093
TI  - Natural history of cervical papilloma virus infection in systemic lupus
      erythematosus - a prospective cohort study.
AB  - OBJECTIVE: To ascertain the incidence, cumulative prevalence, persistence, and
      clearance of human papilloma virus (HPV) infection in patients with systemic
      lupus erythematosus (SLE), and to assess the risk factors for the acquisition and
      persistence of HPV infection. METHODS: One hundred forty-four patients with SLE
      were evaluated at 6-month intervals for up to 3 years. At each visit, a Pap test,
      a test for HPV DNA, and clinical assessment were performed. RESULTS: The
      cumulative prevalence of HPV infection increased significantly (12.5% at baseline
      to 25.0% after 3 years; p = 0.006). Regarding type-specific HPV infection, 18.8%
      patients experienced 68 incident infections. The cumulative prevalence of high
      risk HPV infection (11.1% at baseline to 20.8% after 3 years; p = 0.02) and
      multiple HPV infection also increased significantly (6.9% at baseline to 16.7%
      after 3 years; p = 0.009). Half (33/68, 48.5%) of the incident infections
      persisted for >or= 6 months. Overall, 29/32 (90.6%) of the preexisting infection
      and 10/68 (14.7%) of the incident infections were cleared. Independent risk
      factors associated with incident HPV infection included younger age at first
      sexual intercourse (p = 0.025) and baseline Systemic Lupus International
      Collaborating Clinics score >or= 1 (p = 0.038). Independent risk factor
      associated with persistent HPV infection included preexisting HPV infection (p =
      0.04) and multiple HPV infection during first incident infection (p = 0.02).
      CONCLUSION: High frequency of persistent HPV infection, especially high-risk and
      multiple HPV infection, may explain why squamous intraepithelial lesions occurred
      frequently in patients with SLE. Patients with high inflammatory burden are at
      risk of acquiring HPV infection.

PMID- 20032094
TI  - Grading of inflammatory disease activity in the sacroiliac joints with magnetic
      resonance imaging: comparison between short-tau inversion recovery and gadolinium
      contrast-enhanced sequences.
AB  - OBJECTIVE: We investigated the potential concordance of 2 different magnetic
      resonance (MR) sequences - short-tau inversion recovery (STIR) and fat-saturated
      T1-weighted spin-echo after application of gadolinium (Gd) contrast medium to
      detect active bone marrow abnormalities at the sacroiliac joints (SIJ) in
      patients with spondyloarthritis (SpA). METHODS: Blinded and using the Danish
      scoring method, we evaluated transaxial MR images of the 2 sequences in 40
      patients with SpA with disease duration of 3-14 years. Both the cartilaginous and
      ligamentous portions of the SIJ were analyzed. RESULTS: There was a significant
      positive correlation between the activity scores obtained by STIR and Gd-enhanced
      sequences (p < 0.0001). Agreement in the detection of bone marrow abnormalities
      occurred in 60 of the 80 joints, 35 with and 25 without signs of active disease.
      Discordance with STIR-positive marrow activity scores occurred in only 11 joints;
      Gd-enhanced positive scores in 9 joints. The STIR sequence detected remnants of
      marrow activity in the periphery of chronic fatty replacement not seen or partly
      obscured on the Gd sequence. Small subchondral enhancing lesions may not be
      scored on the STIR sequence, mostly because of reduced image resolution.
      CONCLUSION: Active bone marrow abnormalities were detected nearly equally well
      with STIR and Gd-enhanced fat-suppressed T1 sequences in patients with SpA, with
      STIR being most sensitive to visualize active abnormalities in the periphery of
      chronic changes.

PMID- 20032095
TI  - A novel in vitro model to investigate behavior of articular chondrocytes in
      osteoarthritis.
AB  - OBJECTIVE: To investigate in vivo simulation of the microenvironment in which
      osteoarthritis (OA) chondrocytes are cultured in vitro. METHODS: Human articular
      chondrocytes were cultured under normoxic and hypoxic conditions. Cells were
      cultured on standard culture plastic or a porous polyHEMA surface that closely
      resembles the in vivo cartilage microarchitecture. Morphological changes to the
      cells were demonstrated by fluorescent staining with DAPI and vinculin.
      Proteoglycan and type II collagen protein levels were assessed using established
      techniques. Matrix metalloproteinase-1 (MMP-1) production was assessed by ELISA.
      The gene expression of type II collagen and SOX9 was measured using real-time
      polymerase chain reaction. RESULTS: Cells grown on culture plastic were seen to
      be flat and hexagonal. Cells cultured on the porous polyHEMA surface exhibited
      morphology in keeping with the in vivo microenvironment. Glycosaminoglycan
      release in hypoxia was high from cells cultured on standard culture plastic.
      Transcriptional expression of type II collagen was upregulated in hypoxia and by
      culture on the polyHEMA surface. Transcriptional expression of SOX9 in hypoxia
      was upregulated compared to normoxia; no significant effect was seen by varying
      the culture surface. Translational expression of type II collagen was upregulated
      at 20% oxygen on the polyHEMA surface compared to culture plastic and this was
      related to MMP-1 expression. CONCLUSION: Culture of chondrocytes in hypoxia and
      on a porous surface simulates the in vivo microenvironment and illustrates the
      molecular mechanisms of OA.

PMID- 20032096
TI  - Pancreatitis in systemic lupus erythematosus: frequency and associated factors -
      a review of the Hopkins Lupus Cohort.
AB  - OBJECTIVE: Pancreatitis is a rare but potentially life-threatening complication
      of systemic lupus erythematosus (SLE). Vasculitis of the gastrointestinal tract
      is the most commonly proposed mechanism. We determined the frequency of SLE
      related pancreatitis in the Hopkins Lupus Cohort. METHODS: A large prospective
      cohort of 1811 patients with SLE was reviewed and clinical and laboratory
      measures of SLE patients who developed pancreatitis were compared to patients who
      did not develop pancreatitis. RESULTS: Four percent of patients with SLE had
      pancreatitis due to SLE. The best multivariate model of clinical and laboratory
      associations included hypertriglyceridemia, psychosis, pleurisy, gastritis, and
      anemia. CONCLUSION: Hypertriglyceridemia appears to be a strong associate of
      pancreatitis in SLE, but antiphospholipid antibodies are not. SLE patients with
      psychosis and pleurisy are at increased risk for pancreatitis.

PMID- 20032098
TI  - EQ-5D and SF-36 quality of life measures in systemic lupus erythematosus:
      comparisons with rheumatoid arthritis, noninflammatory rheumatic disorders, and
      fibromyalgia.
AB  - OBJECTIVE: The Medical Outcomes Study Short-form 36 (SF-36) provides numerical
      measurement of patient health, but does not include preferences for health states
      and cannot be used directly in cost-effectiveness analyses. By contrast the
      Euroqol EQ-5D can be used for cost-effectiveness analyses. The EQ-5D has rarely
      been used in systemic lupus erythematosus (SLE). We compared SF-36 and EQ-5D
      values across rheumatic diseases. METHODS: We studied 1316 patients with SLE,
      13,722 with rheumatoid arthritis (RA), 3623 with non-inflammatory rheumatic
      disorders (NIRD), and 2733 with fibromyalgia (FM). RESULTS: The mean EQ-5D,
      physical (PCS) and mental (MCS) component summary scores were 0.72, 36.3, and
      44.3, respectively, in SLE. There was essentially no difference among EQ-5D and
      PCS scores for patients with SLE, RA, or NIRD. MCS was lower in SLE compared with
      RA and NIRD (44.3, 49.1, 50.8, respectively). All scores were more abnormal in FM
      (0.61, 31.9, 41.9). Within SF-36 domains, physical function was better, but
      general health, vitality, social function, role-emotional, and mental health were
      more impaired in SLE compared with RA and NIRD. In SLE, quality of life (QOL) was
      predicted by damage, comorbidity, income, education, and age. Fifteen percent of
      patients with SLE were very satisfied with their health, and their QOL scores
      (0.84, 45.4, 50.1) were similar to those found in the US population for EQ-5D and
      MCS, but were slightly reduced for PCS. CONCLUSION: EQ-5D and PCS are at the same
      levels in SLE as in RA and NIRD, but are more abnormal in SLE in the MCS and
      mental health domains. EQ-5D values allow preference-based comparisons with other
      chronic conditions.

PMID- 20032097
TI  - Association between a CTGF gene polymorphism and systemic sclerosis in a French
      population.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a life-threatening autoimmune disease
      characterized by chronic fibrosis of the skin and internal organs. Connective
      tissue growth factor (CTGF) is believed to be a primary mediator of chronic
      fibrosis. We assessed the possible association between 7 single-nucleotide
      polymorphisms (SNP) in the CTGF gene and scleroderma in a French population
      (registration number 2006/0182). METHODS: We conducted a case-control study with
      241 scleroderma patients and 269 controls. Seven SNP were genotyped using the
      TaqMan system. Univariate and multivariate analyses were performed. In silico
      electrophoretic mobility shift assay (EMSA), and reverse transcriptase polymerase
      chain reaction analyses were done to assess the effect of the SNP on CTGF gene
      expression. RESULTS: The frequency of the rs9399005TT genotype was significantly
      lower in SSc patients than in controls. This association remained significant
      after adjustment for gender. An association was detected between the rs9399005
      and the diffuse and limited cutaneous forms. Multivariate analysis between SSc
      patients and controls taking into account all 7 SNP and sex revealed that only
      sex and the rs9399005 SNP were associated with disease. DNA analysis by EMSA
      indicated that the T allele bound nuclear factors that were also bound by the C
      allele. The binding affinity was higher for the T allele. Analysis of the human
      database and experiments with human hepatocyte cell line indicated the existence
      of an alternative transcript containing the rs9399005 polymorphism in its 3'UTR
      region. In silico analysis indicated that this polymorphism may alter the
      structure of CTGF messenger RNA. CONCLUSION: These findings suggest that CTGF
      gene polymorphisms may contribute to susceptibility to scleroderma.

PMID- 20032099
TI  - Changes in waist circumference and body mass index in relation to changes in
      serum uric acid in Japanese individuals.
AB  - OBJECTIVE: Studies have shown that obesity is associated with an increase in
      serum uric acid; and few data are available on the relationship between changes
      in measures of obesity and changes in uric acid concentrations. We investigated
      the relationship among percentage changes in waist circumference (%dWC), body
      mass index (%dBMI), and serum uric acid (%dUA). METHODS: The data of 3153
      individuals [1968 men, 1185 women (536 premenopausal, 649 postmenopausal)] who
      underwent general health screening over a 2-year period and were not taking
      antihyperuricemic medication were analyzed. RESULTS: Stepwise multiple regression
      analysis showed that %dBMI was associated positively with %dUA in postmenopausal
      women and men, and the association retained statistical significance after
      adjustment for changes in blood pressure and in renal function. Association
      between %dBMI and %dUA was not significant in premenopausal women. In men, %dWC
      was a predicting factor for %dUA, although it did not remain significant when
      %dBMI was used as a covariate in the statistical model. Multivariate logistic
      regression analysis showed that the odds ratio of the association between the
      lowest %dBMI quartile (%dBMI < -1.86) and the lowest %dUA quartile (%dUA < -7.41)
      was 2.04 (95% CI 1.35-3.07) in postmenopausal women and 1.46 (95% CI 1.14-1.86)
      in men. CONCLUSION: Weight loss may represent an effective nonmedical strategy
      for reducing serum UA levels, especially in postmenopausal women and men.

PMID- 20032100
TI  - Vitamin D status and its associations with disease activity and severity in
      African Americans with recent-onset rheumatoid arthritis.
AB  - OBJECTIVE: To examine the prevalence of vitamin D insufficiency and the
      associations of vitamin D concentration with disease status in African Americans
      with rheumatoid arthritis (RA). METHODS: Study participants (n = 266) were
      enrolled in the Consortium for the Longitudinal Evaluation of African Americans
      with Early RA (CLEAR) Registry. The vitamin 25(OH)-D was measured on baseline
      plasma, and associations of 25(OH)-D with disease status (baseline and at 3
      years' disease duration) were examined using univariate and multivariate
      regression. RESULTS: The prevalence of 25(OH)-D insufficiency (<or= 37.5 nmol/l
      or 15 ng/ml) was 50%, with the highest prevalence in winter. In unadjusted
      analyses, vitamin D concentrations were inversely associated with baseline pain
      (p = 0.04), swollen joints (p = 0.04), and Disease Activity Score (DAS28, p =
      0.05) but not with measures at 3 years' disease duration. There were no
      multivariate associations of 25(OH)-D with any disease measures at baseline or at
      3 years, with the exception of a positive borderline association with rheumatoid
      factor positivity at enrollment (p = 0.05). CONCLUSION: Vitamin D insufficiency
      is common in African Americans with recent-onset RA. Unadjusted associations of
      circulating vitamin D with baseline pain, swollen joints, and DAS28 were
      explained by differences in season, age, and gender and were not significant in
      multivariate analyses. In contrast to reports of Northern Europeans with early
      inflammatory arthritis, there are not strong associations of 25(OH)-D
      concentration with symptoms or disease severity in African Americans with RA.

PMID- 20032101
TI  - CXCL 9 and CXCL 10 as Sensitive markers of disease activity in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To assess whether serum levels of CC and CXC chemokines correlate with
      disease activity in patients with rheumatoid arthritis (RA), and to determine
      whether these effects predict clinical response. METHODS: Serum levels of the
      chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at
      baseline and after 12 weeks of treatment with disease-modifying antirheumatic
      drugs or biologic agents in 28 patients using flow cytometry. Serum from 40
      healthy individuals was collected for comparison at baseline. Response to
      treatment was classified according to the European League Against Rheumatism
      (EULAR) response criteria. Remission of disease was defined as a Disease Activity
      Score < 2.6. RESULTS: The baseline serum concentrations of CC and CXC chemokines
      were significantly elevated in patients with active RA compared to healthy
      controls (p < 0.05) except for CCL2. Significant improvement in all disease
      activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%)
      patients achieved good to moderate response based on the EULAR response criteria,
      and 5 (17.9%) patients achieved remission. The improvement in clinical activity
      in patients with RA was accompanied by a significant reduction in the serum
      concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the
      serum level of CXCL10 was also observed in the group that achieved EULAR
      response. Serum concentration of CCL5 remained significantly elevated in patients
      with RA (n = 5) who achieved remission compared to the healthy controls (p <
      0.05). CONCLUSION: Serum concentration of CXCL9 and CXCL10 may serve as sensitive
      biomarkers for disease activity in patients with RA.

PMID- 20032102
TI  - Safety, tolerability, and clinical outcomes after intraarticular injection of a
      recombinant adeno-associated vector containing a tumor necrosis factor antagonist
      gene: results of a phase 1/2 Study.
AB  - OBJECTIVE: To assess safety and clinical outcomes in patients with inflammatory
      arthritis after intraarticular (IA) injection of rAAV2-TNFR:Fc, a recombinant
      adeno-associated viral vector containing the human tumor necrosis factor (TNF)
      receptor-immunoglobulin (IgG1) Fc fusion (TNFR:Fc) gene. METHODS: In this phase
      1/2 randomized study, adults with persistent moderate or severe inflammation in a
      target joint, being treated with or without systemic anti-TNF therapy, received a
      single IA injection of either rAAV2-TNFR:Fc (1 x 10(11), 1 x 10(12), or 1 x
      10(13) DNase-resistant particles/ml joint volume) or placebo, followed by open
      label rAAV2-TNFR:Fc 12-30 weeks later, depending on when the target joint met
      predetermined criteria for reinjection. RESULTS: 127 subjects received the first
      injection of blinded study drug; 95 subjects received open-label rAAV2-TNFR:Fc.
      Administration site reactions, consisting of transient mild to moderate increases
      in tenderness and swelling of the injected joint, occurred after 23/191 (12%)
      rAAV2-TNFR:Fc injections and were dose-dependent. Rates of other adverse events
      were not dose-dependent. Notable serious adverse events (SAE) included culture
      negative septic arthritis in a subject receiving leflunomide and fatal
      disseminated histoplasmosis considered unrelated to rAAV2-TNFR:Fc in a subject
      receiving adalimumab. In the phase 2 portion of the study, a 30% decrease in
      target joint global visual analog scale was observed in 21/50 (42%) rAAV2-TNFR:Fc
      subjects and 3/16 (19%) placebo subjects 12 weeks after first injection (p =
      0.14). CONCLUSION: IA rAAV2-TNFR:Fc resulted in administration site reactions
      after 12% of injections. A fatal SAE, disseminated histoplasmosis, was considered
      not related to study agent. Patient-reported outcome measures of clinical
      response showed greater improvement in treated patients than placebo patients.

PMID- 20032103
TI  - Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the
      Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype
      in Hungarian patients with ankylosing spondylitis.
AB  - OBJECTIVE: Associations have been found between ankylosing spondylitis (AS) and
      polymorphisms in the aminopeptidase regulator of TNFR1 shedding (ARTS1) gene. We
      studied the association of 5 polymorphisms within the ARTS1 gene with AS in
      Hungarian patients. We also investigated the prevalence of HLA-B27 subtypes in
      the Hungarian population. METHODS: A case-control study including 297 patients
      with AS and 200 sex and ethnically matched healthy controls was performed.
      Patients and controls were genotyped for rs27044, rs17482078, rs10050860,
      rs30187, and rs2287987 single-nucleotide polymorphisms using real-time polymerase
      chain reaction (PCR) allelic discrimination. HLA-B27 subtypes were determined
      with PCR sequence-specific primer (PCR-SSP) technique. RESULTS: We observed a
      significant increase in the minor allele frequency of rs27044 (p = 0.001) in the
      AS group compared to controls. The minor allele frequencies of rs10050860 (p =
      0.006) and rs2287987 (p = 0.002) showed a significant decrease in AS patients
      compared to controls. Haplotype analysis revealed association of 2 ARTS1
      haplotypes with AS in the Hungarian population. We found that HLA-B*2705 was the
      predominant subtype in Hungarians with AS. Carriage of the G allele of rs27044
      was significantly associated with the HLA-B*2705 subtype (p = 0.009) in AS
      patients. CONCLUSION: We confirmed reported associations of ARTS1 gene
      polymorphisms with AS in a Hungarian cohort study. We found HLA-B*2705 as the
      predominant subtype in Hungarian AS patients in accord with other studies on
      Caucasian populations. Our results suggest that the ARTS1 gene variants together
      with HLA-B27 strongly contribute to disease susceptibility in patients with AS.

PMID- 20032104
TI  - Linkage and association studies of joint morbidity from rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the relationship between genetic variations of
      rheumatoid arthritis (RA) susceptibility in terms of joint morbidity. METHODS: We
      used data from Genetic Analysis Workshop 15. The Illumina linkage panel IV
      included 5858 single-nucleotide polymorphisms (SNP), with 5744 SNP passing
      quality control filters. The phenotypic variables analyzed were the level of
      rheumatoid factor (RF) and score on the Joint Alignment and Motion (JAM) scale.
      We modified the scale, dividing by RF values relevant to disease severity.
      Linkage analysis for affected sibling pairs was done using the MERLIN program,
      and family-based association tests were carried out using PLINK and FBAT
      software. RESULTS: We found a high peak (LOD = 3.29; NPL Z = 4.07) near the HLA
      DRB1 region on chromosome 6. The linkage at 6p24 at rs1410766 [LOD = 2.66;
      nonparametric linkage (NPL) Z = 3.23] was statistically significant. Two other
      regions also showed possible linkage peaks: chromosome 7q30 at rs322812 (LOD =
      2.47; NPL Z = 3.39) and chromosome 15p34 at rs347117 (LOD = 1.95; NPL Z = 2.80).
      For the family-based association study, 7 SNP related to clinical RA severity
      were detected. CONCLUSION: Genetic variations may lead to an enhanced risk of
      joint damage and increased levels of RF. Further studies are needed to elucidate
      the roles of other genes involved in RA and to explore whether the clinical signs
      of RA are associated with particular genetic variations.

PMID- 20032105
TI  - Incidence of Wegener's granulomatosis in children.
AB  - OBJECTIVE: To determine the incidence and longitudinal trends of Wegener's
      granulomatosis (WG) in the pediatric population of Southern Alberta over the last
      15 years. RESULTS: Fifteen cases of childhood WG were confirmed. The average
      annual incidence was 2.75 cases/million/year, with a steep increase over the last
      5 years to 6.39 cases/million/year. CONCLUSION: In Southern Alberta the incidence
      of childhood WG during the past 15 years was comparable to the incidence reported
      in adults and it seems to be increasing. Further studies are required to
      determine if this is a regional or global phenomenon.

PMID- 20032106
TI  - Negative relationship between expression of glucocorticoid receptor alpha and
      disease activity: glucocorticoid treatment of patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: Glucocorticoid receptor alpha (GRalpha) is crucial for glucocorticoids
      (GC) to carry out their physiological and pharmacological roles. Studies have
      shown the disorder of GR-GC systems in autoimmune diseases. Our study was
      performed to test the relationship between GRalpha expression and disease
      activity of systemic lupus erythematosus (SLE). METHODS: The responses of 55
      patients with SLE to GC were screened. We examined GRalpha mRNA and protein
      expression in peripheral blood mononuclear cells from SLE patients and healthy
      volunteers by reverse transcriptase-polymerase chain reaction and Western
      blotting. RESULTS: Expression of GRalpha in patients with SLE was lower than that
      in controls (p < 0.05). Expression of GRalpha obviously decreased after
      administration of GC in the steroid-sensitive group with SLE (p < 0.05).
      Expression of GRalpha was negatively correlated with SLE Disease Activity Index
      scores in the steroid-sensitive group with SLE. CONCLUSION: The expression of
      GRalpha in patients with SLE was low and there was a negative correlation between
      GRalpha expression and disease activity; these findings might provide insight
      into the pathogenesis of SLE and help to screen whether the patient is sensitive
      to GC treatment. (Heilungkiang Provincial Health Department Guiding Projects
      Funding. Trial registration No. 2006-094.).

PMID- 20032107
TI  - Development and initial validation of a radiographic scoring system for the hip
      in juvenile idiopathic arthritis.
AB  - OBJECTIVE: To develop and validate a radiographic scoring system for the
      assessment of radiographic damage in the hip joint in patients with juvenile
      idiopathic arthritis (JIA). METHODS: The Childhood Arthritis Radiographic Score
      of the Hip (CARSH) assesses and scores these radiographic abnormalities: joint
      space narrowing (JSN), erosion, growth abnormalities, subchondral cysts,
      malalignment, sclerosis of the acetabulum, and avascular necrosis of the femoral
      head. Score validation was accomplished by evaluating reliability and
      correlational, construct, and predictive validity in 148 JIA patients with hip
      disease who had a total of 381 hip radiographs available for study. RESULTS: JSN
      was the most frequently observed radiographic abnormality, followed by erosion
      and sclerosis of the acetabulum. The least common abnormalities were avascular
      necrosis, growth abnormalities, and malalignment. Interobserver and intraobserver
      reliability on baseline and longitudinal score values and on score changes was
      good, with intraclass correlation coefficients ranging from 0.76 to 0.98. Early
      score changes, but not absolute baseline score values, were moderately correlated
      (r(s) > 0.4) with clinical indicators of disease damage at last followup
      observation, thereby demonstrating that the CARSH has good construct and
      predictive validity. The amount of structural damage in the hip radiograph at
      last followup observation was predicted better by baseline to 1-year score change
      (r(s) = 0.66; p < 0.0001) than by absolute baseline score values (r(s) = 0.40; p
      = 0.002). CONCLUSION: Our results show that the CARSH is reliable and valid for
      the assessment of radiographic hip damage and its progression in patients with
      JIA.

PMID- 20032109
TI  - Correlations in concentrations, xylem and phloem flows, and partitioning of
      elements and ions in intact plants. A summary and statistical re-evaluation of
      modelling experiments in Ricinus communis.
AB  - Within the last two decades, a series of papers have dealt with the effects of
      nutrition and nutrient deficiency, as well as salt stress, on the long-distance
      transport and partitioning of nutrients in castor bean. Flows in xylem and phloem
      were modelled according to an empirically-based modelling technique that permits
      additional quantification of the uptake and incorporation into plant organs. In
      the present paper these data were statistically re-evaluated, and new
      correlations are presented. Numerous relationships between different compartments
      and transport processes for single elements, but also between elements, were
      detected. These correlations revealed different selectivities for ions in bulk
      net transport. Generally, increasing chemical concentration gradients for mineral
      nutrients from the rhizosphere to the root and from the xylem to leaf tissue were
      observed, while such gradients decreased from root tissue to the xylem and from
      leaves to the phloem. These studies showed that, for the partitioning of
      nutrients within a plant, the correlated interactions of uptake, xylem and phloem
      flow, as well as loading and unloading of solutes from transport systems, are of
      central importance. For essential nutrients, tight correlations between uptake,
      xylem and phloem flow, and the resulting partitioning of elements, were observed,
      which allows the stating of general models. For non-essential ions like Na(+) or
      Cl(-), a statistically significant dependence of xylem transport on uptake was
      not detected. The central role of the phloem for adjusting, but also signalling,
      of nutrition status is discussed, since strong correlations between leaf nutrient
      concentrations and those in phloem saps were observed. In addition, negative
      correlations between phloem sap sugar concentration and net-photosynthesis,
      growth, and uptake of nutrients were demonstrated. The question remains whether
      this is only a consequence of an insufficient use of carbohydrates in plants or a
      ubiquitous signal for stress in plants. In general, high sugar concentrations in
      phloem saps indicate (nutritional) stress, and high nutrient concentrations in
      phloem saps indicate nutritional sufficiency of leaf tissues.

PMID- 20032108
TI  - Membrane-bound guaiacol peroxidases from maize (Zea mays L.) roots are regulated
      by methyl jasmonate, salicylic acid, and pathogen elicitors.
AB  - Plant peroxidases are involved in numerous cellular processes in plant
      development and stress responses. Four plasma membrane-bound peroxidases have
      been identified and characterized in maize (Zea mays L.) roots. In the present
      study, maize seedlings were treated with different stresses and signal compounds,
      and a functional analysis of these membrane-bound class III peroxidases (pmPOX1,
      pmPOX2a, pmPOX2b, and pmPOX3) was carried out. Total guaiacol peroxidase
      activities from soluble and microsomal fractions of maize roots were compared and
      showed weak changes. By contrast, total plasma membrane and washed plasma
      membrane peroxidase activities, representing peripheral and integral membrane
      proteins, revealed strong changes after all of the stresses applied. A proteomic
      approach using 2D-PAGE analysis showed that pmPOX3 was the most abundant class
      III peroxidase at plasma membranes of control plants, followed by pmPOX2a
      >pmPOX2b >pmPOX1. The molecular mass (63 kDa) and the isoelectric point (9.5) of
      the pmPOX2a monomer were identified for the first time. The protein levels of all
      four enzymes changed in response to multiple stresses. While pmPOX2b was the only
      membrane peroxidase down-regulated by wounding, all four enzymes were
      differentially but strongly stimulated by methyl jasmonate, salicylic acid, and
      elicitors (Fusarium graminearum and Fusarium culmorum extracts, and chitosan)
      indicating their function in pathogen defence. Oxidative stress applied as
      H(2)O(2) treatment up-regulated pmPOX2b >pmPOX2a, while pmPOX3 was down
      regulated. Treatment with the phosphatase inhibitor chantharidin resulted in
      distinct responses.

PMID- 20032110
TI  - Study of the olfactory epithelium in the developing sturgeon. Characterization of
      the crypt cells.
AB  - In acipenserids, crypt cells (CCs) have only been observed in juvenile specimens,
      and it has not been clarified whether they differentiate along with olfactory
      receptor neurons (ORNs) during the lecithotrophic stage or during later
      development stages. Furthermore, no detailed optical microscopy (OM) or electron
      microscopy study on the development of CCs has been published to date. In the
      present study, we used OM and electron microscopy to follow the development of
      CCs in Acipenser naccarii from hatching to the establishment of exogenous
      feeding. Based on these observations, we can affirm that CCs are present from the
      first few posthatching (PH) days. CCs appear with their nucleus close to the
      basal lamina of the epithelium and enveloped by supporting cells. In addition,
      from the beginning of day 2 PH, we observed cells with highly similar
      characteristics to those of CCs (absence of knob, abundant mitochondria and
      filamentous material in apical cytoplasm, numerous microtubules, and envelopment
      by supporting cells) but with cilia still remaining on their noninvaginated
      apical surface. We conclude that these cells may correspond to immature CCs in
      which the crypt, the final feature of their morphological differentiation, has
      not yet formed.

PMID- 20032111
TI  - Characterization of the antennal olfactory system of the bed bug (Cimex
      lectularius).
AB  - The common bed bug Cimex lectularius (Hemiptera; Cimicidae) is a temporary
      ectoparasite on humans that is currently reinvading the developed countries. Like
      other haematophagous arthropods, host seeking and orientation in C. lectularius
      is partially mediated by olfaction. In this study, we reconfirmed the
      distribution of the 44 olfactory sensilla and identified 3 different sensillum
      types located at the distal tip of C. lectularius antenna by external morphology
      mapping. Using a panel of relevant odorants previously reported to be bioactive
      in various haematophagous arthropods, we correlated the morphological mapping
      with an electrophysiological characterization of the olfactory receptor neurons
      housed in each specific sensillum. We found that all 9 grooved peg sensilla
      responded specifically in a dose-dependent manner to ammonia, whereas (E)-2
      hexenal, (E)-2-octenal, dimethyl trisulfide, 6-methyl-5-hepten-2-one, alpha
      pinene, indole, and ethyl butyrate evoked dose-dependent responses within the 6
      smooth peg sensilla. Based on the pattern of response to the tested compounds, we
      were able to separate the 6 smooth peg sensilla of the bed bug into 3 distinct
      functional classes. We compare our results with previous electrophysiological
      recordings made with these compounds on other haematophagous arthropods.

PMID- 20032112
TI  - Coactivation of gustatory and olfactory signals in flavor perception.
AB  - It is easier to detect mixtures of gustatory and olfactory flavorants than to
      detect either component alone. But does the detection of mixtures exceed the
      level predicted by probability summation, assuming independent detection of each
      component? To answer this question, we measured simple response times (RTs) to
      detect brief pulses of one of 3 flavorants (sucrose [gustatory], citral
      [olfactory], sucrose-citral mixture) or water, presented into the mouth by a
      computer-operated, automated flow system. Subjects were instructed to press a
      button as soon as they detected any of the 3 nonwater stimuli. Responses to the
      mixtures were faster (RTs smaller) than predicted by a model of probability
      summation of independently detected signals, suggesting positive coactivation
      (integration) of gustation and retronasal olfaction in flavor perception.
      Evidence for integration appeared mainly in the fastest 60% of the responses,
      indicating that integration arises relatively early in flavor processing. Results
      were similar when the 3 possible flavorants, and water, were interleaved within
      the same session (experimental condition), and when each flavorant was
      interleaved with water only (control conditions). This outcome suggests that
      subjects did not attend selectively to one flavor component or the other in the
      experimental condition and further supports the conclusion that (late) decisional
      or attentional strategies do not exert a large influence on the gustatory
      olfactory flavor integration.

PMID- 20032113
TI  - A timely characterization of vasopressin-sensitive adenylyl cyclase isoforms in
      the mouse inner medullary collecting duct.

PMID- 20032114
TI  - Progressive histone alterations and proinflammatory gene activation: consequences
      of heme protein/iron-mediated proximal tubule injury.
AB  - Rhabdomyolysis (Fe)-induced acute renal failure (ARF) causes renal inflammation,
      and, with repetitive insults, progressive renal failure can result. To gain
      insights into these phenomena, we assessed the impact of a single episode of
      glycerol-induced rhabdomyolysis on proinflammatory/profibrotic [TNF-alpha,
      monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1
      (TGF-beta1)] gene expression and the time course of these changes. CD-1 mice were
      studied 1-7 days after glycerol injection. Normal mice served as controls. RNA
      polymerase II (Pol II) binding to the TNF-alpha, MCP-1, and TGF-beta1 genes,
      "gene-activating" histone modifications [histone 3 lysine 4 (H3K4) trimethylation
      (H3K4m3) and histone 2 variant H2A.Z], and cognate mRNA levels were assessed.
      Results were contrasted to changes in anti-inflammatory heme oxygenase-1 (HO-1).
      Glycerol produced severe ARF (blood urea nitrogen approximately 150-180 mg/dl)
      followed by marked improvement by day 7 (blood urea nitrogen approximately 40
      mg/dl). Early increases in TNF-alpha, MCP-1, and TGF-beta1 mRNAs, Pol II gene
      binding, and H3K4m3/H2A.Z levels were observed. These progressed with time,
      despite resolution of azotemia. Comparable early HO-1 changes were observed.
      However, HO-1 mRNA normalized by day 7, and progressive Pol II binding/histone
      alterations did not occur. Fe-mediated injury to cultured proximal tubule (HK-2)
      cells recapitulated these in vivo results. Hence, this in vitro model was used
      for mechanistic assessments. On the basis of these studies, it was determined
      that 1) the H3K4m3/H2A.Z increases are early events (i.e., they precede mRNA
      increases), 2) subsequent mRNA elevations reflect transcription, not mRNA
      stabilization (actinomycin D assessments), and 3) increased transcription, per
      se, helps sustain elevated H2A.Z levels. We conclude that 1) Fe/glycerol-induced
      tubular injury causes sustained proinflammatory gene activation, 2) decreasing HO
      1 expression, as reflected by mRNA levels, may facilitate this proinflammatory
      state, and 3) gene-activating histone modifications are early injury events and
      progressively increase at selected proinflammatory genes. Thus they may help
      sustain a proinflammatory state, despite resolving ARF.

PMID- 20032115
TI  - Expression and function of CXCL12/CXCR4 in rat urinary bladder with
      cyclophosphamide-induced cystitis.
AB  - Chemokines, otherwise known as chemotactic cytokines, are proinflammatory
      mediators of the immune response and have been implicated in altered sensory
      processing, hyperalgesia, and central sensitization following tissue injury or
      inflammation. To address the role of CXCL12/CXCR4 signaling in normal micturition
      and inflammation-induced bladder hyperreflexia, bladder inflammation in adult
      female Wistar rats (175-250 g) was induced by injecting cyclophosphamide (CYP)
      intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and
      chronic (75 mg/kg; every 3rd day for 10 days) time points. CXCL12, and its
      receptor, CXCR4, were examined in the whole urinary bladder of control and CYP
      treated rats using enzyme-linked immunosorbent assays (ELISAs), quantitative PCR
      (qRT-PCR), and immunostaining techniques. ELISAs, qRT-PCR, and immunostaining
      experiments revealed a significant (P < or = 0.01) increase in CXCL12 and CXCR4
      expression in the whole urinary bladder, and particularly in the urothelium, with
      CYP treatment. The functional role of CXCL12/CXCR4 signaling in micturition was
      evaluated using conscious cystometry with continuous instillation of saline and
      CXCR4 receptor antagonist (AMD-3100; 5 microM) administration in control and CYP
      (48 h)-treated rats. Receptor blockade of CXCR4 using AMD-3100 increased bladder
      capacity in control (no CYP) rats and reduced CYP-induced bladder
      hyperexcitability as demonstrated by significant (P < or = 0.01) increases in
      intercontraction interval, bladder capacity, and void volume. These results
      suggest a role for CXCL12/CXCR4 signaling in both normal micturition and with
      bladder hyperreflexia following bladder inflammation.

PMID- 20032116
TI  - Infusion of angiotensin-(1-7) reduces glomerulosclerosis through counteracting
      angiotensin II in experimental glomerulonephritis.
AB  - Recent identification of a counterregulatory axis of the renin-angiotensin
      system, called angiotensin-converting enzyme 2-angiotensin-(1-7) [ANG-(1-7)]-Mas
      receptor, may offer new targets for the treatment of renal fibrosis. We
      hypothesized that therapy with ANG-(1-7) would improve glomerulosclerosis through
      counteracting ANG II in experimental glomerulonephritis. Disease was induced in
      rats with the monoclonal anti-Thy-1 antibody, OX-7. Based on a three-dose pilot
      study, 576 microg x kg(-1) x day(-1) ANG-(1-7) was continuously infused from day
      1 using osmotic pumps. Measures of glomerulosclerosis include semiquantitative
      scoring of matrix proteins stained for periodic acid Schiff, collagen I, and
      fibronectin EDA+ (FN). ANG-(1-7) treatment reduced disease-induced increases in
      proteinuria by 75%, glomerular periodic acid Schiff staining by 48%, collagen I
      by 24%, and FN by 25%. The dramatic increases in transforming growth factor
      beta1, plasminogen activator inhibitor-1, FN, and collagen I mRNAs seen in
      disease control animals compared with normal rats were all significantly reduced
      by ANG-(1-7) administration (P < 0.05). These observations support our hypothesis
      that ANG-(1-7) has therapeutic potential for reversing glomerulosclerosis.
      Several results suggest ANG-(1-7) acts by counteracting ANG II effects: 1) renin
      expression in ANG-(1-7)-treated rats was dramatically increased as it is with ANG
      II blockade therapy; and 2) in vitro data indicate that ANG II-induced increases
      in mesangial cell proliferation and plasminogen activator inhibitor-1
      overexpression are inhibited by ANG-(1-7) via its binding to a specific receptor
      known as Mas.

PMID- 20032117
TI  - Characterization of connective tissue growth factor expression in primary
      cultures of human tubular epithelial cells: modulation by hypoxia.
AB  - Tubular epithelial cells secrete connective tissue growth factor (CTGF, CCN2),
      which contributes to tubulointerstitial fibrosis. However, the molecular
      regulation of CTGF in human primary tubular epithelial cells (hPTECs) is not well
      defined. Therefore, CTGF expression was characterized in hPTECs isolated from
      healthy parts of tumor nephrectomies, with special emphasis on the regulation by
      transforming growth factor-beta (TGF-beta) and hypoxia, essential factors in the
      development of fibrosis. CTGF synthesis was strongly dependent on cell density.
      High CTGF levels were detected in sparse cells, whereas CTGF expression was
      reduced in confluent cells. Concomitantly, stimulation of CTGF by TGF-beta or the
      histone deacetylase inhibitor trichostatin was prevented in dense cells. Exposure
      of hPTECs to low oxygen tension (1% O2) or the hypoxia mimetic dimethyl
      oxalylglycine for 24 h reduced CTGF gene expression in most of the 17
      preparations analyzed. Preincubation of the cells under hypoxic conditions
      significantly reduced TGF-beta-mediated upregulation of CTGF. In line with these
      data, CTGF mRNA was only induced in interstitial cells, but not in tubular cells
      in kidneys of mice exposed to hypoxia. Longer exposure to hypoxia or TGF-beta (up
      to 72 h) did not induce hPTECs to adopt a mesenchymal phenotype characterized by
      upregulation of alpha-smooth muscle actin, downregulation of E-cadherin, or
      increased sensitivity of the cells in terms of CTGF expression. Sensitivity was
      restored by inhibition of DNA methylation. Taken together, our data provide
      evidence that exposure to hypoxia decreased CTGF gene expression. Furthermore,
      hypoxia per se was not sufficient to induce a mesenchymal phenotype in primary
      tubular epithelial cells.

PMID- 20032118
TI  - Nitro-oleic acid protects against endotoxin-induced endotoxemia and multiorgan
      injury in mice.
AB  - Nitroalkene derivatives of nitro-oleic acid (OA-NO2) are endogenous lipid
      products with potent anti-inflammatory properties in vitro. The present study was
      undertaken to evaluate the in vivo anti-inflammatory effect of OA-NO2 in mice
      given LPS. Two days before LPS administration, C57BL/6J mice were chronically
      infused with vehicle (LPS vehicle) or OA-NO2 (LPS OA-NO2) at 200 microg x kg(-1)
      x day(-1) via osmotic minipumps; LPS was administered via a single
      intraperitoneal (ip) injection (10 mg/kg in saline). A third group received an ip
      injection of saline without LPS or OA-NO2 and served as controls. At 18 h of LPS
      administration, LPS vehicle mice displayed multiorgan dysfunction as evidenced by
      elevated plasma urea and creatinine (kidney), aspartate aminotransferase (AST)
      and alanine aminotransferase (ALT; liver), and lactate dehydrogenase (LDH) and
      reduced ejection fraction (heart). In contrast, the severity of multiorgan
      dysfunction was less in LPS OA-NO2 animals. The levels of circulating TNF-alpha
      and renal TNF-alpha mRNA expression, together with renal mRNA expression of
      monocyte chemoattractant protein-1, ICAM-1, and VCAM-1, and with renal mRNA and
      protein expression of inducible nitric oxide synthase and cyclooxygenase 2, and
      renal cGMP and PGE2 contents, were greater in LPS vehicle vs. control mice, but
      were attenuated in LPS OA-NO2 animals. Similar patterns of changes in the
      expression of inflammatory mediators were observed in the liver. Together,
      pretreatment with OA-NO2 ameliorated the inflammatory response and multiorgan
      injury in endotoxin-induced endotoxemia in mice.

PMID- 20032119
TI  - Expression of transporters involved in urine concentration recovers differently
      after cessation of lithium treatment.
AB  - Patients receiving lithium therapy, an effective treatment for bipolar disorder,
      often present with acquired nephrogenic diabetes insipidus. The nephrotoxic
      effects of lithium can be detected 3 wk after the start of treatment and many of
      these symptoms may disappear in a few weeks after lithium use is stopped. Most
      patients, however, still have a urine-concentrating defect years after ending
      treatment. This prompted an investigation of the transporters involved in the
      urine concentration mechanism, UT-A1, UT-A3, aquaporin-2 (AQP2), and NKCC2, after
      discontinuing lithium therapy. Sprague-Dawley rats fed a Li2CO3-supplemented diet
      produced large volumes of dilute urine after 14 days. After lithium treatment was
      discontinued, urine osmolality returned to normal within 14 days but urine volume
      and urine urea failed to reach basal levels. Western blot and immunohistochemical
      analyses revealed that both urea transporters UT-A1 and UT-A3 were reduced at 7
      and 14 days of lithium treatment and both transporters recovered to basal levels
      14 days after discontinuing lithium administration. Similar analyses demonstrated
      a decrease in AQP2 expression after 7 and 14 days of lithium therapy. AQP2
      expression increased over the 7 and 14 days following the cessation of lithium
      but failed to recover to normal levels. NKCC2 expression was unaltered during the
      14-day lithium regimen but did increase 14 days after the treatment was stopped.
      In summary, the rapid restoration of UT-A1 and UT-A3 as well as the increased
      expression of NKCC2 are critical components to the reestablishment of urine
      concentration after lithium treatment.

PMID- 20032121
TI  - Trastuzumab-related thrombocytopenia: always a self-limiting complication?

PMID- 20032120
TI  - Angiotensin II AT2 receptor regulates ureteric bud morphogenesis.
AB  - ANG II AT2 receptor (AT2R)-deficient mice exhibit abnormal ureteric bud (UB)
      budding, increased incidence of double ureters, and vesicoureteral reflux.
      However, the role of the AT2R during UB morphogenesis and the mechanisms by which
      aberrant AT2R signaling disrupts renal collecting system development have not
      been fully defined. In this study, we mapped the expression of the AT2R during
      mouse metanephric development, examined the impact of disrupted AT2R signaling on
      UB branching, cell proliferation, and survival, and investigated the cross talk
      of the AT2R with the glial-derived neurotrophic factor (GDNF)/c-Ret/Wnt11
      signaling pathway. Embryonic mouse kidneys express AT2R in the branching UB and
      the mesenchyme. Treatment of embryonic day 12.5 (E12.5) metanephroi with the AT2R
      antagonist PD123319 or genetic inactivation of the AT2R in mice inhibits UB
      branching, decreasing the number of UB tips compared with control (34 +/- 1.0 vs.
      43 +/- 0.6, P < 0.01; 36 +/- 1.8 vs. 48 +/- 1.3, P < 0.01, respectively). In
      contrast, treatment of metanephroi with the AT2R agonist CGP42112 increases the
      number of UB tips compared with control (48 +/- 1.8 vs. 39 +/- 12.3, P < 0.05).
      Using real-time quantitative RT-PCR and whole mount in situ hybridization, we
      demonstrate that PD123319 downregulates the expression of GDNF, c-Ret, Wnt11, and
      Spry1 mRNA levels in E12.5 metanephroi grown ex vivo. AT(2)R blockade or genetic
      inactivation of AT2R stimulates apoptosis and inhibits proliferation of the UB
      cells in vivo. We conclude that AT2R performs essential functions during UB
      branching morphogenesis via control of the GDNF/c-Ret/Wnt11 signaling pathway, UB
      cell proliferation, and survival.

PMID- 20032122
TI  - High serum levels of TNF-alpha and IL-6 predict the clinical outcome of treatment
      with human recombinant erythropoietin in anaemic cancer patients.
AB  - BACKGROUND: A number of anaemic cancer patients are not responsive to treatment
      with recombinant human erythropoietin (rHuEPO). The aim of the present study is
      to investigate whether serum levels of tumour necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1beta, IL-6 and additional laboratory parameters, together with
      clinical variables, can predict the clinical outcome of treatment with rHuEPO in
      anaemic cancer patients. PATIENTS AND METHODS: Thirty-five cancer patients and 25
      healthy controls were enrolled in this study. Patients were treated with epoetin
      alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the
      haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6
      of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the
      treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a
      questionnaire for the self-evaluation of cancer-related fatigue. Serum samples
      from patients and control groups were frozen at -80 degrees C and TNF-alpha, IL
      1beta and IL-6 were later examined by enzyme-linked immunosorbent assay. RESULTS:
      Fatigued cancer patients had significant higher levels of circulating TNF-alpha,
      IL-1beta and IL-6 than healthy controls. Responders (Rs) to erythropoietin had
      significant lower medium levels of TNF-alpha and IL-6 than nonresponders (NRs).
      Fatigued patients with a general BFI score > or =6 presented higher medium level
      of cytokines than nonfatigued patients (general BFI score <6), but each group
      responded similarly to treatment with rHuEPO. CONCLUSIONS: High serum levels of
      TNF-alpha and IL-6 at the baseline are significantly correlated with a negative
      response to administration with rHuEPO. Thus, pretreatment evaluation of TNF
      alpha and IL-6 serum levels can help to select those patients who are most likely
      to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell
      count, lactate dehydrogenase and BFI score do not predict the outcome of
      treatment with rHuEPO.

PMID- 20032124
TI  - Erythropoiesis-stimulating agents (ESAs), from chemotherapy-induced anemia to any
      cancer-related anemia?

PMID- 20032123
TI  - Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5
      fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced
      head and neck cancer: a phase II randomized study.
AB  - BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of
      locally advanced squamous cell carcinoma of the head and neck (SCCHN). We
      evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5
      fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS:
      Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group
      performance status of zero to one, were randomly assigned to receive CT/RT alone
      (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800
      mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or
      three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1,
      and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks)
      followed by the same CT/RT. The primary end point was the rate of radiologic
      complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of
      101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates
      were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and
      overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and
      39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT
      were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was
      associated with higher radiologic CR in patients with locally advanced SCCHN with
      no negative impact on CT/RT feasibility.

PMID- 20032125
TI  - Discordant expression of molecular markers between primary and nodal metastases:
      a histopathological manifestation of the 'self (stem cell)-seeding' nature of
      breast cancer disease?

PMID- 20032127
TI  - Lapatinib and metronomic capecitabine combination in an HER2-positive
      inflammatory breast cancer patient: a case report.

PMID- 20032126
TI  - An exploratory study of sunitinib plus paclitaxel as first-line treatment for
      patients with advanced breast cancer.
AB  - BACKGROUND: Sunitinib has shown single-agent activity in patients with previously
      treated metastatic breast cancer (MBC). We investigated the safety of the
      combination of sunitinib and paclitaxel in an exploratory study of patients with
      locally advanced or MBC. METHODS: Patients received oral sunitinib 25 mg/day
      (with escalation to 37.5 mg/day as tolerated) on a continuous daily dosing
      schedule and paclitaxel 90 mg/m(2) on days 1, 8, and 15 of each 28-day cycle.
      Study endpoints included safety (primary endpoint), pharmacokinetics, and
      antitumor activity. RESULTS: Twenty-two patients were enrolled. The most frequent
      adverse events (AEs) were fatigue/asthenia (77%), dysgeusia (68%), and diarrhea
      (64%). Grade 3 AEs included neutropenia (43%), fatigue/asthenia (27%), neuropathy
      (18%), and diarrhea (14%). No drug-drug interaction was observed on the basis of
      pharmacokinetic analysis. Of 18 patients with measurable disease at baseline, 7
      (38.9%) achieved objective responses (including 2 complete and 5 partial
      responses). Clinical responses were observed in three of nine patients with
      triple-negative receptor status (estrogen receptor negative, progesterone
      receptor negative, and human epidermal growth factor receptor-2 negative).
      CONCLUSIONS: These data indicate that sunitinib and paclitaxel in combination are
      well tolerated in patients with locally advanced or MBC. No drug-drug interaction
      was detected and there was preliminary evidence of antitumor activity.

PMID- 20032128
TI  - Swine-origin influenza a (H1N1) viral infection in children: initial chest
      radiographic findings.
AB  - PURPOSE: To evaluate initial chest radiographic findings of swine-origin
      influenza A (S-OIV) (also known as H1N1) viral infection in children. MATERIALS
      AND METHODS: This was an institutional review board-approved, HIPAA-compliant
      retrospective study of 108 patients who had microbiologically confirmed S-OIV
      infection and available initial chest radiographs obtained between April 2009 and
      October 2009. The final study group was divided on the basis of clinical course
      (group 1, outpatients without hospitalization [n = 72]; group 2, inpatients with
      brief hospitalization [n = 22]; group 3, inpatients with intensive care unit
      admission [n = 14]). Two pediatric radiologists blinded to patient group and lung
      parenchymal, airway, pleural, hilar, and mediastinal abnormalities systematically
      reviewed initial chest radiographs. Lung parenchyma and airways were evaluated
      for pattern (peribronchial markings, consolidation, and ground-glass, nodular,
      and reticular opacity), distribution, and extent of abnormalities. Radiographs
      were assessed for presence of pleural effusions or lymphadenopathy. Medical
      records were reviewed for underlying medical conditions and patient outcomes.
      Association between frequency of underlying medical conditions and clinical
      course of S-OIV infection among study groups was evaluated with the Pearson
      chi(2) test. RESULTS: The frequency of normal chest radiographs was significantly
      higher in group 1 (n = 48) than in groups 2 (n = 1) and 3 (n = 0) (P < .001,
      Pearson chi(2) test). Among patients with abnormal radiographs, the most common
      finding in group 1 was prominent peribronchial markings with hyperinflation (n =
      17), whereas the most common findings in groups 2 (n = 12) and 3 (n = 12) were
      bilateral, symmetric, and multifocal areas of consolidation, often associated
      with ground-glass opacities. Nodular opacities, reticular opacities, pleural
      effusion, or lymphadenopathy were not observed in any patient. An increased
      frequency of underlying medical conditions was observed in patients with greater
      severity of illness due to S-OIV infection (group 3, 71%; group 2, 59%; group 1,
      31%) (P = .003, Pearson chi(2) test). All 84 patients with available follow-up
      information have fully recuperated from S-OIV infection. CONCLUSION: Initial
      chest radiographs in children with a mild and self-limited clinical course of S
      OIV infection are often normal, but they may demonstrate prominent peribronchial
      markings with hyperinflation. Bilateral, symmetric, and multifocal areas of
      consolidation, often associated with ground-glass opacities, are the predominant
      radiographic findings in pediatric patients with a more severe clinical course of
      S-OIV infection. (c) RSNA, 2009.

PMID- 20032129
TI  - Science to practice: what does MR oxygenation imaging tell us about human breast
      cancer hypoxia?
AB  - The paradoxical relationship between blood oxygen level-dependent (BOLD) magnetic
      resonance (MR) imaging and breast cancer hypoxia challenges our current
      understanding of what we believe is happening to erythrocytes in tumors. The
      ability of air breathing R2* measurements to reflect tissue hypoxia appears to be
      tumor type-specific, which should prompt further exploration of this image
      contrast mechanism in both human and animal tumors.

PMID- 20032131
TI  - Radiology online: a new look.

PMID- 20032134
TI  - Hedvig Hricak, MD, PhD, Dr(hc), President, Radiological Society of North America,
      2010.

PMID- 20032136
TI  - 2009 RSNA Outstanding Researcher.

PMID- 20032138
TI  - The art and science of medical guidelines: what we know and what we believe.

PMID- 20032139
TI  - CT perfusion imaging of acute stroke: the need for arrival time, delay
      insensitive, and standardized postprocessing algorithms?

PMID- 20032140
TI  - Interdisciplinary teams and the road to discovery.

PMID- 20032141
TI  - Lymphatic metastases from pelvic tumors: anatomic classification,
      characterization, and staging.
AB  - The spread of pelvic tumors to lymph nodes is an important means of tumor
      dissemination. Nodal metastases have important management and prognostic impact.
      Pelvic tumors usually metastasize first to regional lymph nodes, which are
      specific groups of nodes for each tumor, and are classified according to the TNM
      system as N-stage disease. If a pelvic tumor spreads to a lymph node outside of
      the defined regional nodes, this is considered M-stage disease, which usually
      results in upstaging of the disease to overall stage IV cancer and may
      potentially affect the patient's treatment options. Knowledge of the regional
      nodal spread of each tumor is essential in formulating effective search
      strategies for cross-sectional imaging studies performed for staging. Also
      important is correct description of the nomenclature of nodal metastases to
      facilitate proper staging. In this review, the patterns of regional nodal spread
      and N-stage classification are presented for carcinomas of the anus, bladder,
      cervix, endometrium, ovary, penis, prostate, rectum, testis, vagina, and vulva.
      Pelvic lymph node anatomy and nomenclature are reviewed with schematic
      illustrations and clinical examples from patients with pelvic tumors.

PMID- 20032142
TI  - Diffusion-weighted MR imaging of the liver.
AB  - Magnetic resonance (MR) imaging plays an increasingly important role in the
      evaluation of patients with liver disease because of its high contrast
      resolution, lack of ionizing radiation, and the possibility of performing
      functional imaging sequences. With advances in hardware and coil systems,
      diffusion-weighted (DW) MR imaging can now be applied to liver imaging with
      improved image quality. DW MR imaging enables qualitative and quantitative
      assessment of tissue diffusivity (apparent diffusion coefficient) without the use
      of gadolinium chelates, which makes it a highly attractive technique,
      particularly in patients with severe renal dysfunction at risk for nephrogenic
      systemic fibrosis. In this review, acquisition parameters, postprocessing, and
      quantification methods applied to liver DW MR imaging will be discussed. The
      current clinical uses of DW MR imaging (liver lesion detection and
      characterization, compared and combined with conventional sequences) and the
      emerging applications of DW MR imaging (tumor treatment response and diagnosis of
      liver fibrosis and cirrhosis) will be reviewed. Also, limitations, mainly image
      quality and reproducibility of diffusion parameters, and future directions of
      liver DW MR imaging will be discussed.

PMID- 20032144
TI  - Acute myocardial infarction: serial cardiac MR imaging shows a decrease in
      delayed enhancement of the myocardium during the 1st week after reperfusion.
AB  - PURPOSE: To evaluate the time course of delayed gadolinium enhancement of
      infarcted myocardium by using serial contrast agent-enhanced (CE) cardiac
      magnetic resonance (MR) images obtained during the acute, subacute, and chronic
      stages of infarction. MATERIALS AND METHODS: The study protocol was reviewed and
      approved by the local ethics committee, and written informed consent was
      obtained. Seventeen patients with reperfused acute myocardial infarction (AMI)
      underwent cine and CE cardiac MR a median of 1, 7, 35, and 180 days after
      reperfusion. Infarct size determined on the basis of delayed enhancement MR
      imaging at different times was compared by using nonparametric tests and Bland
      Altman analysis. Extent of myocardial enhancement was compared with single photon
      emission computed tomographic (SPECT) measures of infarct size with Spearman
      correlation. Regional myocardial enhancement extent and contractility were
      analyzed with nonparametric tests. RESULTS: Infarct size was 18.3% of total
      myocardial LV volume on day 1 after AMI and decreased to 12.9% on day 7, 11.3% on
      day 35, and 11.6% on day 180 (all P < .001). Estimated infarct size on day 7, as
      compared with day 1 enhancement size, declined by 57.1% within the epicardium and
      by 6.3% within the endocardium (both P < .001). Infarct size on day 7 showed only
      minor changes at subsequent imaging and yielded a high correlation with SPECT
      measurements of infarct size (r = 0.84). Infarct size on day 7 inversely
      correlated with long-term wall thickening (P < .0001) and allowed prediction of
      contractile function. CONCLUSION: In patients with AMI and successful coronary
      reperfusion, the size of delayed gadolinium enhancement at CE cardiac MR imaging
      significantly diminished during the 1st week after infarction. Thus, timing of CE
      cardiac MR imaging is crucial for accurate measurement of myocardial infarct size
      early after AMI.

PMID- 20032143
TI  - Reasons women at elevated risk of breast cancer refuse breast MR imaging
      screening: ACRIN 6666.
AB  - PURPOSE: To determine reasons for nonparticipation in a trial of supplemental
      screening with magnetic resonance (MR) imaging after mammography and
      ultrasonography (US). MATERIALS AND METHODS: Women(n = 2809) at elevated risk of
      breast cancer were enrolled in the American College of Radiology Imaging Network
      6666 US Screening Protocol at 21 institutions. Fourteen institutions met
      technical and experience requirements for this institutional review board
      approved, HIPAA-compliant substudy of supplemental screening with MR imaging.
      Those women who had completed 0-, 12-, and 24-month screenings with mammography
      combined with US were considered for a single contrast material-enhanced MR
      examination within 8 weeks after completing the 24-month mammography-US
      screening. A total of 1593 women had complete MR substudy registration data: 378
      of them were ineligible for the study, and 1215 had analyzable data. Reasons for
      nonparticipation were determined. Demographic data were compared between study
      participants and nonparticipants. RESULTS: Of 1215 women with analyzable data,
      703 (57.9%), with a mean age of 54.8 years, were enrolled in the MR substudy and
      512 (42.1%) declined participation. Women with a 25% or greater lifetime risk of
      breast cancer were more likely to participate (odds ratio, 1.53; 95% confidence
      interval: 1.10, 2.12). Of 512 nonparticipants, 130 (25.4%) refused owing to
      claustrophobia; 93 (18.2%), owing to time constraints; 62 (12.1%), owing to
      financial concerns; 47 (9.2%), because their physician would not provide a
      referral and/or did not believe MR imaging was indicated; 40 (7.8%), because they
      were not interested; 39 (7.6%), because they were medically intolerant to MR
      imaging; 29 (5.7%), because they did not want to undergo intravenous injection;
      27 (5.3%), owing to additional biopsy or other procedures that might be required
      subsequently; 21 (4.1%), owing to MR imaging scheduling constraints; 11 (2.2%),
      because of the travel required; seven (1.4%), owing to gadolinium-related risks
      or allergies; and six (1.2%), for unknown reasons. CONCLUSION: Of 1215 women with
      elevated breast cancer risk who could, according to protocol guidelines, undergo
      breast MR imaging, only 57.9% agreed to participate.

PMID- 20032145
TI  - Intrinsic susceptibility MR imaging of chemically induced rat mammary tumors:
      relationship to histologic assessment of hypoxia and fibrosis.
AB  - PURPOSE: To investigate relationships between magnetic resonance (MR) imaging
      measurements of R2* and carbogen-induced DeltaR2* in vivo with subsequent
      histologic assessment of grade, hypoxia, fibrosis, and necrosis in a chemically
      induced rat mammary tumor model. MATERIALS AND METHODS: All experiments were
      performed in accordance with the local ethics review panel, the UK Home Office
      Animals Scientific Procedures Act of 1986, and the UK Co-ordinating Committee on
      Cancer Research guidelines. Of 30 rats injected with N-methyl-N-nitrosourea, 17
      developed mammary tumors. Prior to MR imaging, rats were administered
      pimonidazole. Tumor R2* was then quantified while the host first breathed air and
      then carbogen (95% O(2), 5% CO(2); n = 16). Tumor sections were subsequently
      stained for pimonidazole, sirius red, cytokeratin 14, and hematoxylin-eosin for
      quantitative assessment of hypoxia, fibrosis, malignancy, and necrosis,
      respectively, and graded according to the Scarff-Bloom-Richardson scale. Linear
      regression analysis was used to identify any correlates of the MR imaging data
      with histologic data. RESULTS: Tumors exhibited wide heterogeneity in the
      magnitude of carbogen-induced reduction in R2*, an emerging imaging biomarker of
      fractional blood volume. Significant correlations were found between pimonidazole
      adduct formation and both baseline tumor R2* (r = -0.54, P = .03) and carbogen
      induced DeltaR2* (r = 0.56, P = .02), demonstrating that tumors with a larger
      fractional blood volume were less hypoxic. There was also a significant
      correlation between pimonidazole and sirius red staining (r = 0.76, P < .01),
      indicating that more fibrotic tumors were also more hypoxic. There were no
      correlations of R2* with grade. CONCLUSION: In this model of breast cancer,
      baseline tumor R2* and carbogen-induced DeltaR2* are predictive imaging
      biomarkers for hypoxia and primarily determined by blood volume.

PMID- 20032146
TI  - Quantification of hepatic steatosis with 3-T MR imaging: validation in ob/ob
      mice.
AB  - PURPOSE: To validate quantitative imaging techniques used to detect and measure
      steatosis with magnetic resonance (MR) imaging in an ob/ob mouse model of hepatic
      steatosis. MATERIALS AND METHODS: The internal research animal and resource
      center approved this study. Twenty-eight male ob/ob mice in progressively
      increasing age groups underwent imaging and were subsequently sacrificed. Six
      ob/+ mice served as control animals. Fat fraction imaging was performed with a
      chemical shift-based water-fat separation method. The following three methods of
      conventional fat quantification were compared with imaging: lipid extraction and
      qualitative and quantitative histologic analysis. Fat fraction images were
      reconstructed with single- and multiple-peak spectral models of fat and with and
      without correction for T2* effects. Fat fraction measurements obtained with the
      different reconstruction methods were compared with the three methods of fat
      quantification, and linear regression analysis and two-sided and two-sample t
      tests were performed. RESULTS: Lipid extraction and qualitative and quantitative
      histologic analysis were highly correlated with the results of fat fraction
      imaging (r(2) = 0.92, 0.87, 0.82, respectively). No significant differences were
      found between imaging measurements and lipid extraction (P = .06) or quantitative
      histologic (P = .07) measurements when multiple peaks of fat and T2* correction
      were included in image reconstruction. Reconstructions in which T2* correction,
      accurate spectral modeling, or both were excluded yielded lower agreement when
      compared with the results yielded by other techniques. Imaging measurements
      correlated particularly well with histologic grades in mice with low fat
      fractions (intercept, -1.0% +/-1.2 [standard deviation]). CONCLUSION: MR imaging
      can be used to accurately quantify fat in vivo in an animal model of hepatic
      steatosis and may serve as a quantitative biomarker of hepatic steatosis.

PMID- 20032147
TI  - Carbogen gas-challenge BOLD MR imaging in a rat model of diethylnitrosamine
      induced liver fibrosis.
AB  - PURPOSE: To investigate the relationship between gas-challenge blood oxygen level
      dependent (BOLD) magnetic resonance (MR) imaging measurements and hepatic disease
      progression in a rat model of diethylnitrosamine (DEN)-induced liver fibrosis.
      MATERIALS AND METHODS: The institutional animal care and use committee approved
      all experiments. Liver fibrosis was induced in 27 male Wistar rats by means of
      weekly oral gavage with 5 mL of 1.5% DEN solution per kilogram of body weight for
      3-11 weeks, which produced varying degrees of liver fibrosis. Eight rats
      developed nonsubstantial fibrosis; eight rats, substantial fibrosis; and 15 rats,
      cirrhosis. Four nontreated healthy rats served as controls. Multiple-gradient
      echo MR images were acquired in the rats at steady-state normoxia and hyperoxia
      and then during dynamic gas challenges. The change in R2* (DeltaR2*) during the
      gas challenge and the ratio of number of activated voxels to total number of
      voxels in the liver were quantified. Masson trichrome staining of liver tissue
      was used to identify collagen tissue. Liver fibrosis was assessed by using a
      semiquantitative METAVIR scoring system and quantitative analysis of the
      percentage of liver fibrosis. Hepatic hemodynamic responses at BOLD MR imaging
      were compared across the fibrosis stages at independent-sample t test and linear
      regression analyses. RESULTS: DeltaR2* was well correlated with gas-challenge
      interval. Mean DeltaR2* decreased during liver fibrosis progression, from 19.60
      sec(-1) +/- 4.47 (standard deviation) in animals without substantial fibrosis to
      14.02 sec(-1) +/- 2.88 and 6.26 sec(-1) +/- 7.40 in animals with substantial
      fibrosis and cirrhosis, respectively (P = .006 for rats without vs rats with
      substantial fibrosis, P = .001 for rats with substantial fibrosis vs rats with
      cirrhosis, P < .001 for rats without substantial fibrosis vs rats with
      cirrhosis). Mean DeltaR2* (r = -0.773) and liver activation (r = -0.691) were
      inversely correlated with liver fibrosis (P < .001). CONCLUSION: Carbogen gas
      challenge BOLD MR imaging can depict hepatic hemodynamic alterations during the
      progression of fibrosis and has the potential to serve as a noninvasive,
      nonenhanced imaging method for liver fibrosis diagnosis and staging.

PMID- 20032148
TI  - Bowel preparation for CT colonography: blinded comparison of magnesium citrate
      and sodium phosphate for catharsis.
AB  - PURPOSE: To compare colonic cleansing and fluid retention of double-dose
      magnesium citrate with those of single-dose sodium phosphate in patients
      undergoing computed tomographic (CT) colonography. MATERIALS AND METHODS: This
      retrospective HIPAA-compliant clinical study had institutional review board
      approval; informed consent was waived. The study included 118 consecutive
      patients given single-dose sodium phosphate for bowel catharsis and 115
      consecutive patients at risk for phosphate nephropathy, who were instead given
      double-dose magnesium citrate. The bowel preparation regimen was otherwise
      identical. Four-point scales were used to assess residual stool and fluid in the
      six colonic segments, and attenuation of residual fluid was measured. An a priori
      power analysis was performed, and unpaired t tests with Welch correction were
      used to compare the two groups on stool and fluid scores and fluid attenuation.
      RESULTS: Both cathartic regimens offered excellent colon cleansing, with no
      significant difference for residual stool in any of the six segments. Stool
      scores of 1 or 2 (ie, no residual stool or residual stool <5 mm) were recorded in
      88.6% (627 of 708) of colonic segments in the sodium phosphate group and in 88.1%
      (608 of 690) in the magnesium citrate group. No clinically important differences
      were seen in residual fluid scores in any of the six segments, with the only
      significant difference seen in the sigmoid colon (2.17 for sodium phosphate vs
      2.44 for magnesium citrate; P< 0.01). Fluid attenuation was significantly
      different between magnesium citrate and sodium phosphate groups (790 HU +/- 216
      vs 978 HU +/- 160; P <.001). CONCLUSION: Both sodium phosphate and magnesium
      citrate provided excellent colon cleansing for CT colonography. Residual stool
      and fluid were similar in both groups, and fluid attenuation values were closer
      to optimal in the magnesium citrate group. Since bowel preparation provided by
      both cathartics was comparable, magnesium citrate should be considered for CT
      colonography, particularly in patients at risk for phosphate nephropathy.

PMID- 20032149
TI  - Low-tube-voltage, high-tube-current multidetector abdominal CT: improved image
      quality and decreased radiation dose with adaptive statistical iterative
      reconstruction algorithm--initial clinical experience.
AB  - PURPOSE: To investigate whether an adaptive statistical iterative reconstruction
      (ASIR) algorithm improves the image quality at low-tube-voltage (80-kVp), high
      tube-current (675-mA) multidetector abdominal computed tomography (CT) during the
      late hepatic arterial phase. MATERIALS AND METHODS: This prospective, single
      center HIPAA-compliant study was institutional review board approved. Informed
      patient consent was obtained. Ten patients (six men, four women; mean age, 63
      years; age range, 51-77 years) known or suspected to have hypervascular liver
      tumors underwent dual-energy 64-section multidetector CT. High- and low-tube
      voltage CT images were acquired sequentially during the late hepatic arterial
      phase of contrast enhancement. Standard convolution FBP was used to reconstruct
      140-kVp (protocol A) and 80-kVp (protocol B) image sets, and ASIR (protocol C)
      was used to reconstruct 80-kVp image sets. The mean image noise; contrast-to
      noise ratio (CNR) relative to muscle for the aorta, liver, and pancreas; and
      effective dose with each protocol were assessed. A figure of merit (FOM) was
      computed to normalize the image noise and CNR for each protocol to effective
      dose. Repeated-measures analysis of variance with Bonferroni adjustment for
      multiple comparisons was used to compare differences in mean CNR, image noise,
      and corresponding FOM among the three protocols. The noise power spectra
      generated from a custom phantom with each protocol were also compared. RESULTS:
      When image noise was normalized to effective dose, protocol C, as compared with
      protocols A (P = .0002) and B (P = .0001), yielded an approximately twofold
      reduction in noise. When the CNR was normalized to effective dose, protocol C
      yielded significantly higher CNRs for the aorta, liver, and pancreas than did
      protocol A (P = .0001 for all comparisons) and a significantly higher CNR for the
      liver than did protocol B (P = .003). Mean effective doses were 17.5 mSv +/- 0.6
      (standard error) with protocol A and 5.1 mSv +/- 0.3 with protocols B and C.
      Compared with protocols A and B, protocol C yielded a small but quantifiable
      noise reduction across the entire spectrum of spatial frequencies. CONCLUSION:
      Compared with standard FBP reconstruction, an ASIR algorithm improves image
      quality and has the potential to decrease radiation dose at low-tube-voltage,
      high-tube-current multidetector abdominal CT during the late hepatic arterial
      phase.

PMID- 20032150
TI  - Differentiation of malignant thrombus from bland thrombus of the portal vein in
      patients with hepatocellular carcinoma: application of diffusion-weighted MR
      imaging.
AB  - PURPOSE: To investigate the utility of diffusion-weighted (DW) imaging in
      distinguishing bland thrombus from neoplastic thrombus in the portal vein in
      patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this
      retrospective institutional review board-approved HIPAA-complaint study, the
      imaging results in 25 patients (16 men [average age, 62.3 years; range, 35-75
      years] and nine women [average age, 58.4 years; range, 32-69 years]; overall
      average age, 60.1 years; range, 32-75 years) with HCC and portal vein thrombosis
      who were examined with both contrast material-enhanced computed tomography (CT)
      and 1.5-T magnetic resonance (MR) imaging were reviewed. Axial echo-planar two
      dimensional DW imaging was performed by using b values of 50, 400, and 800
      sec/mm(2). A thrombus was considered neoplastic if it expanded the vessel or
      enhanced on the dynamic CT and MR images; otherwise it was considered bland. The
      signal intensity (SI) of the thrombus and HCC lesions in the same patients was
      compared on DW images. The results were evaluated by using the Fisher exact test.
      The apparent diffusion coefficients (ADCs) of HCC and thrombus were used to
      compute the ratio of the ADC of the thrombus to the ADC of the tumor. RESULTS: On
      DW images, 15 of 19 neoplastic thrombi demonstrated same SI and four showed lower
      SI than the primary HCC. Each of the six bland thrombi had lower SI than the
      primary HCC (P < .001). The mean ADC of HCC and thrombus in the neoplastic
      thrombus group was 0.87 x 10(-3) mm(2)/sec and 0.88 x 10(-3) mm(2)/sec,
      respectively (P = .45). The ADC of the bland thrombus was 2.89 x 10(-3)
      mm(2)/sec, significantly higher than the ADC of the HCC (1.0 x 10(-3) mm(2)/sec,
      P < .0003). The ratio of the ADC of the thrombus to the ADC of the tumor in the
      bland thrombus group was 2.9 compared with 0.998 in the neoplastic group (P =
      .0003). CONCLUSION: DW imaging enables discrimination between bland and
      neoplastic portal vein thrombi when the ratio of the ADC of the thrombus to the
      ADC of HCC was lower than 2 and when the thrombi showed similar SI as the primary
      HCC when qualitative analysis was performed.

PMID- 20032151
TI  - Characterization of adrenal lesions: comparison of 2D and 3D dual gradient-echo
      MR imaging at 3 T--preliminary results.
AB  - PURPOSE: To retrospectively compare a two-dimensional (2D) and a three
      dimensional (3D) technique for in-phase (IP) and opposed-phase (OP) single-breath
      hold 3-T magnetic resonance (MR) imaging in the characterization of adrenal
      lesions, with histopathologic confirmation, computed tomographic findings, or
      imaging follow-up for a minimum of 6 months used as the reference standard.
      MATERIALS AND METHODS: This retrospective HIPAA-compliant study was approved by
      institutional review board, and a waiver of informed consent was obtained. Thirty
      four patients (mean age, 57 years) with 37 adrenal lesions underwent 3-T adrenal
      MR imaging with both 2D and 3D single-breath-hold dual gradient-echo (GRE) MR
      sequences. Signal intensity (SI) index and adrenal-to-spleen, adrenal-to-liver,
      and adrenal-to-muscle SI ratios for each lesion were compared between the two
      techniques by using repeated-measures analysis of variance. The area under the
      receiver operating characteristic curve (AUC) for each evaluation method was
      determined, with retrospective selection of suggested thresholds. RESULTS: For
      the 2D and 3D techniques, the mean SI index and SI ratios were significantly
      different between adenomas and nonadenomas (P < .05), except for the adrenal-to
      liver SI ratio with the 2D technique and the adrenal-to-muscle SI ratio with both
      techniques. For all evaluation methods, the AUCs were higher, although not
      statistically significant, for the 3D technique. The two techniques exploited
      different suggested thresholds for discriminating adenomas from nonadenomas.
      CONCLUSION: Adrenal adenomas can be readily differentiated from nonadenomas at 3
      T MR imaging with either a 2D or 3D single-breath-hold dual GRE MR technique.
      Depending on the acquisition technique, different suggested thresholds need to be
      selected for various evaluation methods.

PMID- 20032152
TI  - Synthetic-echo time postprocessing technique for generating images with variable
      T2-weighted contrast: diagnosis of meniscal and cartilage abnormalities of the
      knee.
AB  - PURPOSE: To assess the feasibility and accuracy of a synthetic-echo time (TE)
      magnetic resonance (MR) postprocessing technique for the diagnostic evaluation of
      abnormalities of menisci and articular cartilage in the knee. MATERIALS AND
      METHODS: This study was approved by the institutional review board. Twenty-four
      patients (three women, 21 men; mean age, 44.8 years) gave informed written
      consent to prospectively undergo evaluation of their knees (10 left and 14 right
      knees) with standard sagittal intermediate-weighted (repetition time msec/TE
      msec, 2200/17) and fat-saturated T2-weighted (3600/88) fast spin-echo sequences.
      In addition, sagittal multiecho fast gradient-echo sequences were performed for
      the generation of synthetic-TE images with variable T2- or T2(*)-weighted
      contrast by using a newly developed synthetic-TE analysis tool that was
      incorporated directly into the picture archiving and communication system.
      Sensitivity, specificity, and accuracy values for detection of lesions in menisci
      and articular cartilage were calculated by using findings at surgery as reference
      standard. RESULTS: The standard intermediate-weighted and fat-suppressed T2
      weighted MR sequences had overall sensitivity, specificity, and accuracy values
      of 100% and 100%, 88% and 93%, and 95% and 95% for the diagnosis of tears of
      medial and lateral menisci, respectively, as well as sensitivity, specificity,
      and accuracy values of 82%, 97%, and 95%, respectively, for articular cartilage
      defects. Corresponding sensitivity, specificity, and accuracy values for
      multiecho MR imaging with synthetic-TE MR image generation were 92% and 100%, 88%
      and 87%, and 90% and 90% for the diagnosis of tears of medial and lateral
      menisci, respectively, as well as sensitivity, specificity, and accuracy values
      of 70%, 99%, and 95%, respectively, for articular cartilage defects. CONCLUSION:
      For the evaluation of menisci and articular cartilage, images generated with the
      synthetic-TE technique are a potentially viable alternative to standard T2
      weighted images obtained at different TEs. Furthermore, the synthetic-TE approach
      allowed assessment of abnormalities of menisci and articular cartilage with high
      sensitivity and specificity.

PMID- 20032153
TI  - Differences in CT perfusion maps generated by different commercial software:
      quantitative analysis by using identical source data of acute stroke patients.
AB  - PURPOSE: To examine the variability in the qualitative and quantitative results
      of computed tomographic (CT) perfusion imaging generated from identical source
      data of stroke patients by using commercially available software programs
      provided by various CT manufacturers. MATERIALS AND METHODS: Institutional review
      board approval and informed consent were obtained. CT perfusion imaging data of
      10 stroke patients were postprocessed by using five commercial software packages,
      each of which had a different algorithm: singular-value decomposition (SVD),
      maximum slope (MS), inverse filter (IF), box modulation transfer function (bMTF),
      and by using custom-made original software with standard (sSVD) and block
      circulant (bSVD) SVD methods. Areas showing abnormalities in cerebral blood flow
      (CBF), mean transit time (MTT), and cerebral blood volume (CBV) were compared
      with each other and with the final infarct areas. Differences among the ratios of
      quantitative values in the final infarct areas and those in the unaffected side
      were also examined. RESULTS: The areas with CBF or MTT abnormalities and the
      ratios of these values significantly varied among software, while those of CBV
      were stable. The areas with CBF or MTT abnormalities analyzed by using SVD or
      bMTF corresponded to those obtained with delay-sensitive sSVD, but overestimated
      the final infarct area. The values obtained from software by using MS or IF
      corresponded well with those obtained from the delay-insensitive bSVD and the
      final infarct area. Given the similarities between CBF and MTT, all software were
      separated in two groups (ie, sSVD and bSVD). The ratios of CBF or MTTs correlated
      well within both groups, but not across them. CONCLUSION: CT perfusion imaging
      maps were significantly different among commercial software even when using
      identical source data, presumably because of differences in tracer-delay
      sensitivity.

PMID- 20032154
TI  - Alzheimer disease: functional abnormalities in the dorsal visual pathway.
AB  - PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered
      activation compared with age-matched healthy control (HC) subjects during a task
      that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The
      study was performed in accordance with the Declaration of Helsinki, with
      institutional ethics committee approval, and all subjects provided written
      informed consent. Two tasks were performed to investigate neural function: face
      matching and location matching. Twelve patients with mild AD and 14 age-matched
      HC subjects were included. Brain activation was measured by using functional
      magnetic resonance imaging. Group statistical analyses were based on a mixed
      effects model corrected for multiple comparisons. RESULTS: Task performance was
      not statistically different between the two groups, and within groups there were
      no differences in task performance. In the HC group, the visual perception tasks
      selectively activated the visual pathways. Conversely in the AD group, there was
      no selective activation during performance of these same tasks. Along the dorsal
      visual pathway, the AD group recruited additional regions, primarily in the
      parietal and frontal lobes, for the location-matching task. There were no
      differences in activation between groups during the face-matching task.
      CONCLUSION: The increased activation in the AD group may represent a compensatory
      mechanism for decreased processing effectiveness in early visual areas of
      patients with AD. The findings support the idea that the dorsal visual pathway is
      more susceptible to putative AD-related neuropathologic changes than is the
      ventral visual pathway.

PMID- 20032155
TI  - Assessment of metabolic response to radioimmunotherapy with 90Y-ibritumomab
      tiuxetan in patients with relapsed or refractory B-cell non-Hodgkin lymphoma.
AB  - PURPOSE: To prospectively compare the assessment of metabolic response to yttrium
      90 ((90)Y)-ibritumomab tiuxetan radioimmunotherapy (RIT) by using fluorine 18
      ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomographic-computed
      tomographic (PET/CT) imaging at 2 and 6 months to determine the most appropriate
      time to detect therapeutic response in refractory non-Hodgkin lymphoma (NHL)
      patients treated with RIT. MATERIALS AND METHODS: The ethical committee of the
      university approved the protocol and all patients signed informed consent. Twenty
      three consecutive patients (10 women, 13 men; mean age, 51.8 years +/-7.3
      [standard deviation]) treated by using RIT for relapsed or refractory follicular
      NHL were enrolled. For all patients, (18)F FDG PET/CT scanning was performed at
      baseline and at 2 and 6 months after RIT. Response was assessed by using the
      International Workshop Criteria (IWC) and revised criteria (IWC + PET) as well as
      the criteria of the European Organization for Research and Treatment of Cancer.
      One-way analysis of variance for repeated measures, receiver operator curve
      analysis, and Kaplan-Meier curves were used for statistical analysis. RESULTS:
      PET/CT performed at 2 months revealed complete (n = 12) or partial (n = 4)
      metabolic response in 16 of 23 patients with complete or partial clinical
      response. These findings were all confirmed at 6-month scanning. PET/CT indicated
      refractory or persistent disease at 2 and 6 months in the remaining seven
      patients. Better overall survival was observed for patients with a reduction in
      the maximum standard uptake value of 49% or higher (both at 2 and 6 months after
      RIT) when compared with those with a decrease of less than 49% (P < .05).
      CONCLUSION: Early assessment of response to RIT by using PET/CT might be useful
      in the identification of patients needing additional therapeutic strategies.

PMID- 20032156
TI  - Brachial plexus birth injury: US screening for glenohumeral joint instability.
AB  - PURPOSE: To prospectively evaluate the use and optimal timing of ultrasonographic
      (US) screening for posterior shoulder subluxation in infantswith brachial plexus
      birth injury (BPBI). MATERIALS AND METHODS: Approval of the ethics committee and
      informed consent of guardians was obtained. This population-based prospective
      study included neonates with BPBI who were born in Helsinki from January 1, 2003
      through December 31, 2006, and in whom BPBI was verified with sequential clinical
      examinations. US was performed at 1, 3, 6, and 12 months. Size (width and height)
      of the humeral head and its ossification center and congruency of the shoulder
      (alpha angle) were measured. Frequency of BPBI and permanent changes were
      evaluated. This study also included patients who were referred from the tertiary
      catchment area. For statistical analysis, 95% confidence intervals were
      calculated, and analysis of variance was performed. RESULTS: BPBI was seen in 132
      of 41980 neonates (3.1 per 1000). In 27 cases (0.64 per 1000), BPBI did not heal
      during the 1st year of life and was considered permanent. The humeral head and
      its ossification center were smaller on the affected side in permanent BPBI. Nine
      patients with permanent palsy had posterior subluxation of the humeral head
      depicted with US (alpha angle, >30 degrees ). In five patients, posterior
      subluxation [corrected] was detected at 3 months. Nineteen of 21 patients with
      BPBI from the tertiary catchment area had permanent palsy. Ten of 19 patients
      developed posterior subluxation of the shoulder, which was verified with US.
      Altogether, three of these cases were not detected by surgeons. Posterior
      subluxation of the humeral head developed during the 1st year of life in one
      third of patients with permanent BPBI. In more than one-half (55% [five of nine])
      of the patients, posterior subluxation [corrected] was detected with US at 3
      months, and in 89% (eight of nine), it was detected at 6 months. CONCLUSION: US
      is a fast and useful tool for diagnosis of posterior subluxation of the humeral
      head, and examination of the glenohumeral joint should be performed at 3 and 6
      months of age in infants with BPBI if symptoms persist.

PMID- 20032157
TI  - Systematic review of current guidelines, and their evidence base, on risk of
      lactic acidosis after administration of contrast medium for patients receiving
      metformin.
AB  - PURPOSE: To systematically review evidence about the relationship between
      metformin administration and the use of iodinated contrast medium and risk of
      lactic acidosis (LA) and to assess the quality of five current guidelines for use
      of contrast medium in patients who are taking metformin. MATERIALS AND METHODS: A
      search strategy was developed by using search termsrelated to metformin, contrast
      media, and LA. Searches were conducted in MEDLINE (Ovid), all Evidence-based
      Medicine Reviews (Ovid), EMBASE, and Cochrane library databases and were
      augmented with searches for evidence-based guidelines on radiology and evidence
      based medicine Web sites by using the Google Internet search engine. Guidelines
      were appraised by two independent reviewers by using the Appraisal of Guidelines
      Research and Evaluation Collaboration Instrument. Other studies were appraised by
      using structured appraisal checklists. RESULTS: Five guidelines were identified
      and five empirical studies met inclusion criteria. All guidelines had poor scores
      on some Appraisal of Guidelines for Research and Evaluation (AGREE) Collaboration
      criteria; poorer scores tended to occur in relation to objective assessment of
      rigor of guideline development, editorial independence, and applicability of the
      guideline to clinical practice. Lack of agreement was observed among guidelines
      about the need to stop taking metformin after contrast medium is administered,
      risk of LA in patients with normal renal function before contrast medium
      injection, recommended method of measuring renal function, and values used to
      define abnormal function. The evidence that was used as a basis for determining
      the guidelines for metformin administration, use of contrast medium, and risk of
      LA consisted of a limited number of observational studies, including case
      reports, summaries of case reports, and case series (National Health and Medical
      Research Council of Australia level IV-V evidence). More important, it was not
      apparent that a systematic search strategy had been used to identify the studies
      referenced by the guidelines nor that the referenced studies had been appraised.
      Individual guideline recommendations were not clearly connected to cited
      references. CONCLUSION: Substantial inconsistencies exist between the
      recommendations of the five international guidelines about contrast medium
      administration in patients who are taking metformin. These are, in part, caused
      by the low level of evidence underpinning guideline recommendations.

PMID- 20032158
TI  - Focal cystic high-attenuation lesions: characterization in renal phantom by using
      photon-counting spectral CT--improved differentiation of lesion composition.
AB  - PURPOSE: To evaluate the capability of spectral computed tomography (CT) to
      improve the characterization of cystic high-attenuation lesions in a renal
      phantom and to test the hypothesis that spectral CT will improve the
      differentiation of cystic renal lesions with high protein content and those that
      have undergone hemorrhage or malignant contrast-enhancing transformation.
      MATERIALS AND METHODS: A renal phantom that contained cystic lesions grouped in
      nonenhancing cyst and hemorrhage series and an iodine-enhancing series was
      developed. Spectral CT is based on new detector designs that may possess energy
      sensitive photon-counting abilities, thereby facilitating the assessment of
      quantitative information about the elemental and molecular composition of tissue
      or contrast materials. Imaging of the renal phantom was performed with a
      prototype scanner at 20 mAs and 70 keV, allowing characterization of x-ray
      photons at 25-34, 34-39, 39-44, 44-49, 49-55, and more than 55 keV. Region of
      interest analysis was used to determine lesion attenuation values at various x
      ray energies. Statistical analysis was performed to assess attenuation patterns
      and identify distinct levels of attenuation on the basis of curve regression
      analysis with analysis of variance tables. RESULTS: Spectral CT depicted linear
      clusters for the cyst (P < .001, R(2) > 0.940) and hemorrhage (P < .001, R(2) >
      0.962) series without spectral overlap. A distinct linear attenuation profile
      without spectral overlap was also detected for the iodine-enhancing series (P <
      .001, R(2) > 0.964), with attenuation values attained in the 34-39-keV energy bin
      statistically identified as outliers (mean slope variation, >37%), corresponding
      with iodine k-edge effects at 33.2 keV. CONCLUSION: Spectral CT has the potential
      to enable distinct characterization of hyperattenuating fluids in a renal phantom
      by helping identify proteinaceous and hemorrhagic lesions through assessment of
      their distinct levels of attenuation as well as by revealing iodine-containing
      lesions through analysis of their specific k-edge discontinuities.

PMID- 20032160
TI  - Primary non-small cell lung cancer: review of frequency, location, and time of
      recurrence after radiofrequency ablation.
AB  - PURPOSE: To review the recurrence patterns in patients with primary non-small
      cell lung cancer (NSCLC) treated with percutaneous image-guided radiofrequency
      (RF) ablation. MATERIALS AND METHODS: This retrospective review was institutional
      review board approved and HIPAA compliant. Informed consent was waived. Data from
      all patients with primary NSCLC who underwent lung RF ablation from January 1998
      to January 2008 were reviewed. Ninety-one patients were identified. Ten patients
      with no posttreatment imaging results and two patients with multiple treated lung
      cancers were excluded. There were 79 tumors in 79 patients (mean age, 75 years).
      Mean tumor size was 2.5 cm (range, 1-5.5 cm). Fifteen (19%) tumors were central,
      and 64 (81%) tumors were peripheral. Nineteen (24%) patients underwent adjuvant
      external beam radiation, and nine (11%) patients underwent concomitant
      brachytherapy. Correlation of computed tomography and positron emission
      tomography imaging studies with biopsy results, tumor size, location, and stage
      was performed. Patterns of recurrence were classified as local, intrapulmonary,
      nodal, mixed (local and nodal), and distant. RESULTS: Forty-five (57%) patients
      demonstrated no evidence of recurrence at follow-up imaging (range, 1-72 months;
      mean, 17 months). Recurrence was seen in 34 (43%) patients (range, 2-48 months;
      mean, 14 months). Recurrence after RF ablation was local in 13 (38%),
      intrapulmonary in six (18%), nodal in six (18%), mixed in two (6%), and distant
      metastases in seven (21%) cases. Median disease-free survival was 23 months. Sex,
      tumor location, and radiation therapy were not associated with risk of
      recurrence. Increasing tumor size (P = .02) and stage (P = .007) were related to
      risk of recurrence. CONCLUSION: The most common pattern of recurrence was local,
      which suggests that more aggressive initial RF ablation and adjuvant radiation
      may offer improvement in outcomes. Continued follow-up imaging is needed because
      new recurrences were seen throughout the 2 years following treatment.

PMID- 20032162
TI  - Case 153: atypical tumefactive hypertrophic cardiomyopathy.

PMID- 20032159
TI  - Characterization of metabolic differences between benign and malignant tumors:
      high-spectral-resolution diffuse optical spectroscopy.
AB  - PURPOSE: To develop a near-infrared spectroscopic method to identify breast
      cancer biomarkers and to retrospectively determine if benign and malignant breast
      lesions could be distinguished by using this method. MATERIALS AND METHODS: The
      study was HIPAA compliant and was approved by the university institutional review
      board. Written informed consent was obtained. By using self-referencing
      differential spectroscopy (SRDS) analysis, the existence of specific
      spectroscopic signatures of breast lesions on images acquired by using diffuse
      optical spectroscopy imaging in the wavelength range (650-1000 nm) was
      established. The SRDS method was tested in 60 subjects (mean age, 38 years; age
      range, 22-74 years). There were 17 patients with benign breast tumors and 22
      patients with malignant breast tumors. There were 21 control subjects. RESULTS:
      Discrimination analysis helped separate malignant from benign tumors. A total of
      40 lesions (22 malignant and 18 benign) were analyzed. Twenty were true-positive
      lesions, 17 were true-negative lesions, one was a false-positive lesion, and two
      were false-negative lesions (sensitivity, 91% [20 of 22]; specificity, 94% [17 of
      18]; positive predictive value, 95% [20 of 21]; and negative predictive value,
      89% [17 of 19]). CONCLUSION: The SRDS method revealed localized tumor biomarkers
      specific to pathologic state.

PMID- 20032163
TI  - Should CT angiography be routinely used in patients suspected of having
      aneurysmal subarachnoid hemorrhage? No!

PMID- 20032165
TI  - Frequent attendance of primary care out-of-hours services in the Netherlands:
      characteristics of patients and presented morbidity.
AB  - BACKGROUND: Over the last years, a system of regional general practices was
      developed in The Netherlands, responsible for the primary care out-of-hours
      services (OHS). As in daytime, frequent attendance of the OHS increases workload
      and the health care; detailed description of the background of frequent
      attendance is required to develop interventions aiming at reduction. OBJECTIVES:
      To assess the characteristics of the frequent attenders (FAs) and the presented
      morbidity during their consultations and to study the persistence of frequent
      attendance. METHODS: We performed a retrospective descriptive 1-year database
      investigation of all patient contacts (n = 44 953) made in 2007 with the OHS 'de
      Gelderse Vallei'. We analysed characteristics of normal attender, FA and very
      frequent attender (VFA) and compared the reason for encounter, GP diagnoses,
      psychiatric co-morbidities and management during their 2007 consultations.
      RESULTS: VFAs, constituting 1% of the attenders and 7.7% of the total number of
      contacts, more often reported agitation as reason for encounter. The prevalence
      of psychiatric diagnosis in the VFA group (15.3%) was significantly higher than
      in other groups. Reassurance was the most frequent prevalent management action in
      each group. The prevalence of chronic diseases and psychological problems was
      higher in the VFA groups. CONCLUSIONS: Frequent attendance puts severe pressure
      on OHS resources. Much of the frequent attendance can be explained by the
      increased incidence of chronic diseases and psychiatric co-morbidity.

PMID- 20032164
TI  - Natural and artificial RNAs occupy the same restricted region of sequence space.
AB  - Different chemical and mutational processes within genomes give rise to sequences
      with different compositions and perhaps different capacities for evolution. The
      evolution of functional RNAs may occur on a "neutral network" in which sequences
      with any given function can easily mutate to sequences with any other. This
      neutral network hypothesis is more likely if there is a particular region of
      composition that contains sequences that are functional in general, and if many
      different functions are possible within this preferred region of composition. We
      show that sequence preferences in active sites recovered by in vitro selection
      combine with biophysical folding rules to support the neutral network hypothesis.
      These simple active-site specifications and folding preferences obtained by
      artificial selection experiments recapture the previously observed purine bias
      and specific spread along the GC axis of naturally occurring aptamers and
      ribozymes isolated from organisms, although other types of RNAs, such as miRNA
      precursors and spliceosomal RNAs, that act primarily through complementarity to
      other amino acids do not share these preferences. These universal evolved
      sequence features are therefore intrinsic in RNA molecules that bind small
      molecule targets or catalyze reactions.

PMID- 20032166
TI  - Attitudes of women with menstrual disorders to the use of clinical guidelines in
      their care.
AB  - BACKGROUND: Despite their growing influence on patient management and outcomes,
      very little is known about patients' perceptions of clinical guidelines. This is
      a significant omission, particularly for services advocating patient-centred care
      and informed decision making. OBJECTIVES: To explore the knowledge and attitudes
      of women with menstrual disorders towards the use of evidence-based clinical
      guidelines for their condition. METHODS: Semi-structured interviews were
      conducted with women with menstrual disorders. RESULTS: Some women were not aware
      of the existence of clinical guidelines for their condition. Many were unsure as
      to their exact nature. The most consistent interpretation of guidelines was as a
      'set of rules'. Numerous positive aspects of the use of guidelines were
      identified, for example, ensuring quality and safety for patients, earlier
      diagnosis, reducing waiting times and improving continuity of care. Negative
      views involved seeing guidelines as a tool for rationing and concerns over
      inflexibility. Patients recognized that implementation of guidelines in general
      practice can be problematic, especially if resources are not made available. An
      unmet need for information became apparent in this group of patients. Many women
      felt that they should have access to guidelines that are being used in their
      medical care and that guidelines had the potential to act as an information
      resource for patients. CONCLUSIONS: A patient-centred service should endeavour to
      increase patient awareness of the existence and use of clinical guidelines. A
      patient version of clinical guidelines may be useful in promoting patients
      involvement in decision making and may improve outcomes.

PMID- 20032167
TI  - Reducing resistance to diabetes treatment using short narrative interventions.
AB  - OBJECTIVE: This article presents a narrative-based technique, which allows
      medical personnel to empower patients with diabetes and improve adherence.
      METHODS: The study was undertaken in Maccabi Healthcare Services, among 123
      patients diagnosed with diabetes. Four empathic narratives were constructed,
      referring to different factors influencing resistance to treatment, as were
      identified by the Resistance to Treatment Questionnaire. Each narrative contains
      statements typical for patients whose resistance to treatment is influenced by a
      particular factor. An Empathic Narratives Evaluation Questionnaire was designed
      for this study. It contained three items, assessing the correlation of a specific
      empathic narrative with the patient's attitude and their reasons for resistance
      to treatment. The patients were asked to indicate whether they recognize these
      narratives as describing their reasons for resistance. Three empathic narratives
      were read to each patient: two narratives were matched for the two major
      categories of resistance for each patient and one narrative related to a category
      of resistance that received the lowest score. RESULTS: The narratives were found
      to correspond to the core reasons for resistance to diabetes treatment.
      Significant difference was found also between the scores of the empathic
      narrative related to the second strongest reason for resistance to treatment and
      the empathic narrative related to the weakest reason for resistance to treatment.
      This finding supports testimonial validity of the narratives. CONCLUSION: Short
      narrative interventions demonstrated in this study can be used by health care
      professionals as a working tool that provides the possibility reducing the
      patient's reasons for resistance to treatment.

PMID- 20032169
TI  - Tailoring advice and optimizing response: a case study of a telephone-based
      support for patients with type 2 diabetes.
AB  - BACKGROUND AND AIMS: Health care increasingly incorporates telephone counselling,
      but the dynamics of interactions supporting its delivery are not well understood.
      This paper explores how advice was packaged and received by participants with
      type 2 diabetes within the context of a Pro-Active Call-Centre Treatment Support
      (PACCTS) system delivered to provide diabetes self-care training over the
      telephone. METHODS: The data relate to nine participants who formed part of the
      qualitative evaluation within the intervention arm of a randomized controlled
      trial (n = 591) of PACCTS. One consultation call between the tele-carer and the
      participant was tape recorded towards the end of the 3-year study and each
      participant was interviewed by telephone within 24 hours of the consultation. The
      nine calls and interviews were transcribed and analysed using the constant
      comparative method. RESULTS: The type of advice the participants received was
      packaged in six forms: advice as explanation, general information-giving, generic
      advice, advice in the form of practitioner self-disclosure, personalized advice
      and responsive advice. Variation was evident in terms of the nature of advice
      provided, level of generality, form and context. CONCLUSIONS: As the participants
      had to make multiple behavioural changes over time, advice needed to be
      delivered, reiterated and reinforced to achieve understanding and uptake. The
      more specific and personalized the information and advice, the more likely it was
      for the participant to give a positive and engaged response. Seizing every
      opportunity to deliver good quality personalized and/or responsive advice is
      essential in order to facilitate effective behavioural change.

PMID- 20032168
TI  - Patients' views of receiving lessons in the Alexander technique and an exercise
      prescription for managing back pain in the ATEAM trial.
AB  - BACKGROUND: Lessons in the Alexander Technique and exercise prescription proved
      effective for managing low back pain in primary care in a clinical trial.
      OBJECTIVES: To understand trial participants' expectations and experiences of the
      Alexander Technique and exercise prescription. METHODS: A questionnaire assessing
      attitudes to the intervention, based on the Theory of Planned Behaviour, was
      completed at baseline and 3-month follow-up by 183 people assigned to lessons in
      the Alexander Technique and 176 people assigned to exercise prescription. Semi
      structured interviews to assess the beliefs contributing to attitudes to the
      intervention were carried out at baseline with14 people assigned to the lessons
      in the Alexander Technique and 16 to exercise prescription, and at follow-up with
      15 members of the baseline sample. RESULTS: Questionnaire responses indicated
      that attitudes to both interventions were positive at baseline but became more
      positive at follow-up only in those assigned to lessons in the Alexander
      Technique. Thematic analysis of the interviews suggested that at follow-up many
      patients who had learned the Alexander Technique felt they could manage back pain
      better. Whereas many obstacles to exercising were reported, few barriers to
      learning the Alexander Technique were described, since it 'made sense', could be
      practiced while carrying out everyday activities or relaxing, and the teachers
      provided personal advice and support. CONCLUSION: Using the Alexander Technique
      was viewed as effective by most patients. Acceptability may have been superior to
      exercise because of a convincing rationale and social support and a better
      perceived fit with the patient's particular symptoms and lifestyle.

PMID- 20032170
TI  - A primary care pragmatic cluster randomized trial of the use of home blood
      pressure monitoring on blood pressure levels in hypertensive patients with above
      target blood pressure.
AB  - BACKGROUND: The measurement of blood pressure (BP) at home by patients with
      hypertension is increasingly used to assess and monitor BP. Evidence for its
      effectiveness in improving BP control is mixed. METHODS: To determine if home BP
      monitoring improves BP a pragmatic cluster randomized contolled trial was carried
      out in family practices in southeastern Ontario, Canada. Family practice patients
      with uncontrolled hypertension were recruited to the trail. Patients were divided
      into two groups: one with at least weekly measurements of BP at home, recording
      those measurements and showing those to the family physician during office visits
      for hypertension and the control group were given usual care. The primary outcome
      was mean awake BP on ambulatory monitoring at 6- and 12-month follow-up and the
      secondary outcomes were mean BP on full 24-hour ambulatory blood pressure
      monitoring (ABPM), mean sleep BP on ABPM and BP on the BpTRU device, all at 6-
      and 12-month follow-up. RESULTS: Home BP monitoring did not improve BP compared
      to usual care at 12-month follow-up: mean awake systolic BP on ABPM [141.1 versus
      142.8 mmHg, mean difference 1.7 mmHg; 95% confidence interval (CI) -0.6 to 4.0, P
      = 0.314] and mean awake diastolic BP on ABPM (78.7 versus 79.4 mmHg, mean
      difference 0.7 mmHg; 95% CI -7.7 to 9.1, P = 0.398). Similar negative results
      were obtained for men and women separately. However, outcomes using the full 24
      hour ABPM and the BpTRU device showed a significantly lower diastolic BP at 12
      months. When analysis was done by sex, this effect was shown to be only in men.
      CONCLUSION: Home BP monitoring may improve BP control in men with hypertension.

PMID- 20032171
TI  - Human genetic variation recognizes functional elements in noncoding sequence.
AB  - Noncoding DNA, particularly intronic DNA, harbors important functional elements
      that affect gene expression and RNA splicing. Yet, it is unclear which specific
      noncoding sites are essential for gene function and regulation. To identify
      functional elements in noncoding DNA, we characterized genetic variation within
      introns using ethnically diverse human polymorphism data from three public
      databases-PMT, NIEHS, and SeattleSNPs. We demonstrate that positions within
      introns corresponding to known functional elements involved in pre-mRNA splicing,
      including the branch site, splice sites, and polypyrimidine tract show reduced
      levels of genetic variation. Additionally, we observed regions of reduced genetic
      variation that are candidates for distance-dependent localization sites of
      functional elements, possibly intronic splicing enhancers (ISEs). Using several
      bioinformatics approaches, we provide additional evidence that supports our
      hypotheses that these regions correspond to ISEs. We conclude that studies of
      genetic variation can successfully discriminate and identify functional elements
      in noncoding regions. As more noncoding sequence data become available, the
      methods employed here can be utilized to identify additional functional elements
      in the human genome and provide possible explanations for phenotypic
      associations.

PMID- 20032172
TI  - Herpes simplex virus type 1 immediate-early protein ICP22 is required for VICE
      domain formation during productive viral infection.
AB  - During productive infection, herpes simplex virus type 1 (HSV-1) induces the
      formation of discrete nuclear foci containing cellular chaperone proteins,
      proteasomal components, and ubiquitinated proteins. These structures are known as
      VICE domains and are hypothesized to play an important role in protein turnover
      and nuclear remodeling in HSV-1-infected cells. Here we show that VICE domain
      formation in Vero and other cells requires the HSV-1 immediate-early protein
      ICP22. Since ICP22 null mutants replicate efficiently in Vero cells despite being
      unable to induce VICE domain formation, it can be concluded that VICE domain
      formation is not essential for HSV-1 productive infection. However, our findings
      do not exclude the possibility that VICE domain formation is required for viral
      replication in cells that are nonpermissive for ICP22 mutants. Our studies also
      show that ICP22 itself localizes to VICE domains, suggesting that it could play a
      role in forming these structures. Consistent with this, we found that ICP22
      expression in transfected cells is sufficient to reorganize the VICE domain
      component Hsc70 into nuclear inclusion bodies that resemble VICE domains. An N
      terminal segment of ICP22, corresponding to residues 1 to 146, is critical for
      VICE domain formation in infected cells and Hsc70 reorganization in transfected
      cells. We previously found that this portion of the protein is dispensable for
      ICP22's effects on RNA polymerase II phosphorylation. Thus, ICP22 mediates two
      distinct regulatory activities that both modify important components of the host
      cell nucleus.

PMID- 20032173
TI  - Vesicular stomatitis virus genomic RNA persists in vivo in the absence of viral
      replication.
AB  - Our previous studies using intranasal inoculation of mice with vesicular
      stomatitis virus (VSV) vaccine vectors showed persistence of vector genomic RNA
      (gRNA) for at least 60 days in lymph nodes in the absence of detectable
      infectious virus. Here we show high-level concentration of virus and gRNA in
      lymph nodes after intramuscular inoculation of mice with attenuated or single
      cycle VSV vectors as well as long-term persistence of gRNA in the lymph nodes. To
      determine if the persistence of gRNA was due to ongoing viral replication, we
      developed a tagged-primer approach that was critical for detection of VSV mRNA
      specifically. Our results show that VSV gRNA persists long-term in the lymph
      nodes while VSV mRNA is present only transiently. Because VSV transcription is
      required for replication, our results indicate that persistence of gRNA does not
      result from continuing viral replication. We also performed macrophage depletion
      studies that are consistent with initial trapping of VSV gRNA largely in lymph
      node macrophages and subsequent persistence elsewhere in the lymph node.

PMID- 20032174
TI  - Identification of the CD163 protein domains involved in infection of the porcine
      reproductive and respiratory syndrome virus.
AB  - Scavenger receptor CD163 is a key entry mediator for porcine reproductive and
      respiratory syndrome virus (PRRSV). To identify the CD163 protein domains
      involved in PRRSV infection, deletion mutants and chimeric mutants were created.
      Infection experiments revealed that scavenger receptor cysteine-rich (SRCR)
      domain 5 (SRCR 5) is essential for PRRSV infection, while the four N-terminal
      SRCR domains and the cytoplasmic tail are not required. The remaining CD163
      protein domains need to be present but can be replaced by corresponding SRCR
      domains from CD163-L1, resulting in reduced (SRCR 6 and interdomain regions) or
      unchanged (SRCR 7 to SRCR 9) infection efficiency. In addition, CD163-specific
      antibodies recognizing SRCR 5 are able to reduce PRRSV infection.

PMID- 20032175
TI  - The structure of the poxvirus A33 protein reveals a dimer of unique C-type lectin
      like domains.
AB  - The current vaccine against smallpox is an infectious form of vaccinia virus that
      has significant side effects. Alternative vaccine approaches using recombinant
      viral proteins are being developed. A target of subunit vaccine strategies is the
      poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of
      Poxviridae that is expressed on the outer viral envelope. Here we have determined
      the structure of the A33 ectodomain of vaccinia virus. The structure revealed C
      type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five
      different crystal lattices. Comparison of the A33 dimer models shows that the A33
      monomers have a degree of flexibility in position within the dimer. Structural
      comparisons show that the A33 monomer is a close match to the Link module class
      of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell
      receptor class of CTLDs. Structural data on Link modules and NK-cell receptor
      ligand complexes suggest a surface of A33 that could interact with viral or host
      ligands. The dimer interface is well conserved in all known A33 sequences,
      indicating an important role for the A33 dimer. The structure indicates how
      previously described A33 mutations disrupt protein folding and locates the
      positions of N-linked glycosylations and the epitope of a protective antibody.

PMID- 20032176
TI  - Infection of cell lines with experimental and natural ovine scrapie agents.
AB  - Mouse bioassay remains the gold standard for determining proof of infectivity,
      strain type, and infectious titer estimation in prion disease research. The
      development of an approach using ex vivo cell-based assays remains an attractive
      alternative, both in order to reduce the use of mice and to hasten results. The
      main limitation of a cell-based approach is the scarcity of cell lines permissive
      to infection with natural transmissible spongiform encephalopathy strains. This
      study combines two advances in this area, namely, the standard scrapie cell assay
      (SSCA) and the Rov9 and MovS6 cell lines, which both express the ovine PrP VRQ
      allele, to assess to what extent natural and experimental ovine scrapie can be
      detected ex vivo. Despite the Rov9 and MovS6 cell lines being of different
      biological origin, they were both permissive and resistant to infection with the
      same isolates of natural sheep scrapie as detected by SSCA. Rov9 subclones that
      are 20 times more sensitive than Rov9 to SSBP/1-like scrapie infection were
      isolated, but all the subclones maintained their resistance to isolates that
      failed to transmit to the parental line. The most sensitive subclone of the Rov9
      cell line was used to estimate the infectious titer of a scrapie brain pool
      (RBP1) and proved to be more sensitive than the mouse bioassay using wild-type
      mice. Increasing the sensitivity of the Rov9 cell line to SSBP/1 infection did
      not correlate with broadening susceptibility, as the specificity of
      permissiveness and resistance to other scrapie isolates was maintained.

PMID- 20032177
TI  - Multi-low-dose mucosal simian immunodeficiency virus SIVmac239 challenge of
      cynomolgus macaques immunized with "hyperattenuated" SIV constructs.
AB  - Hyperattenuated simian immunodeficiency virus SIVmac239-derived constructs Delta5
      CMV and Delta6-CCI are an effort to render SIV incapable of, in practical terms,
      both reversion and recombination while maintaining the immune features of SIV as
      a retrovirus. Primary inoculation of cynomolgus macaques with 10(8) 50% tissue
      culture infective doses (TCID(50)) of Delta5-CMV or Delta6-CCI induced low-level
      humoral and cellular responses detectable in the absence of measureable in vivo
      replication. The first of three DNA boosts resulted in elevated gamma interferon
      (IFN-gamma) enzyme-linked immunospot (ELISPOT) responses to Gag, Pol, and Env in
      the Delta5-CMV vaccine group compared to the Delta6-CCI vaccine group (P =
      0.001). Weekly intrarectal challenge with a low dose of SIVmac239 followed by a
      dose escalation was conducted until all animals became infected. The mean peak
      viral load of the Delta5-CMV-vaccinated animals (3.7 x 10(5) copies/ml) was
      approximately 1 log unit lower than that of the control animals. More
      dramatically, the viral load set point of these animals was decreased by 3 log
      units compared to that of the controls (<50 versus 1.64 x 10(4) copies/ml; P <
      0.0001). Seventy-five percent (6/8) of vaccine recipients controlled virus below
      1,000 copies/ml for at least 6 months, with a subset controlling virus and
      maintaining substantial CD4 T-cell counts for close to 2 years of follow-up. The
      correlates of protection from SIV disease progression may lie in the rapidity and
      protective value of immune responses that occur early in primary SIV infection.
      Prior immunization with hyperattenuated SIVmac239, even if sterilizing immunity
      is not achieved, may allow a more advantageous host response.

PMID- 20032178
TI  - Vaccinia virus particles mix inefficiently, and in a way that would restrict
      viral recombination, in coinfected cells.
AB  - It is well established that poxviruses are subjected to genetic recombination,
      but attempts to map vaccinia virus genes using classical genetic crosses were
      historically confounded by high levels of experimental noise and a poor
      correlation between physical and genetic map distances. These virus-by-virus
      crosses also never produced the 50% recombinant progeny that should be seen in
      experiments involving distant markers. Poxviruses replicate in membrane-wrapped
      cytoplasmic structures called virosomes (or factories) and we have developed a
      method for tracking the development of these structures using live cell imaging
      and cells expressing phage lambda Cro protein fused to enhanced green fluorescent
      protein (EGFP). The EGFP-cro protein binds nonspecifically to DNA and permits
      live cell imaging of developing vaccinia virus factories. Using this method, we
      see virosomes first appearing about 4 to 5 h postinfection. The early virosomes
      exhibit a compact appearance and then, after a period of exponential growth
      lasting several hours, blur and start to dissipate in a process presumably linked
      to viral packaging. During the growth period, the virosomes migrate toward the
      nuclear periphery while colliding and fusing at a rate dependent upon the numbers
      of infecting particles. However, even at high multiplicities of infection (10
      PFU/cell), we estimate approximately 20% of the virosomes never fuse. We have
      also used fluorescence in situ hybridization (FISH) methods to study virosomes
      formed by the fusion of viruses carrying different gene markers. FISH showed that
      DNA mixes rather poorly within fused virosomes and the amount of mixing is
      inversely dependent on the time between virosome appearance and fusion. Our
      studies suggest that the intracellular movement and mixing of virosomes create
      constraints that reduce opportunities for forming recombinants and that these
      phenomena create outcomes reflected in classical poxvirus genetics.

PMID- 20032179
TI  - The latency-associated nuclear antigen interacts with MeCP2 and nucleosomes
      through separate domains.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells express the latency
      associated nuclear antigen (LANA) involved in the regulation of host and viral
      gene expression and maintenance of the KSHV latent episome. Performance of these
      diverse functions involves a 7-amino-acid chromatin-binding motif (CBM) situated
      at the amino terminus of LANA that is capable of binding directly to nucleosomes.
      LANA interacts with additional chromatin components, including methyl-CpG-binding
      protein 2 (MeCP2). Here, we show that the carboxy-terminal DNA
      binding/dimerization domain of LANA provides the principal interaction with MeCP2
      but that this association is modulated by the CBM. Both domains are required for
      LANA to colocalize with MeCP2 at chromocenters, regions of extensive pericentric
      heterochromatin that can be imaged by fluorescence microscopy. Within MeCP2, the
      methyl-CpG-binding domain (MBD) is the primary determinant for chromatin
      localization and acts together with the adjacent repression domains (the
      transcription repression domain [TRD] and the corepressor-interacting domain
      [CRID]) to redirect LANA to chromocenters. MeCP2 facilitates repression by LANA
      bound to the KSHV terminal repeats, a function that requires the MeCP2 C terminus
      in addition to the MBD and CRID/TRD. LANA and MeCP2 can also cooperate to
      stimulate transcription of the human E2F1 promoter, which lacks a LANA DNA
      binding sequence, but this function requires both the N and C termini of LANA.
      The ability of LANA to establish multivalent interactions with histones and
      chromatin-binding proteins such as MeCP2 would enable LANA to direct regulatory
      complexes to specific chromosomal sites and thereby achieve stable reprogramming
      of cellular gene expression in latently infected cells.

PMID- 20032180
TI  - Viral sanctuaries during highly active antiretroviral therapy in a nonhuman
      primate model for AIDS.
AB  - Highly active antiretroviral therapy (HAART) enables long-term suppression of
      plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds
      following cessation of therapy. During HAART, this virus resides in latently
      infected cells, such as resting CD4(+) T cells, and in other cell types that may
      support residual virus replication. Therapeutic eradication will require
      elimination of virus from all reservoirs. We report here a comprehensive analysis
      of these reservoirs in fluids, cells, and tissues in a rhesus macaque model that
      mimics HAART in HIV-infected humans. This nonhuman primate model uses RT-SHIV, a
      chimera of simian immunodeficiency virus containing the HIV-1 reverse
      transcriptase (RT). Methods were developed for extraction, preamplification, and
      real-time PCR analyses of viral DNA (vDNA) and viral RNA (vRNA) in tissues from
      RT-SHIV-infected macaques. These methods were used to identify viral reservoirs
      in RT-SHIV-infected macaques treated with a potent HAART regimen consisting of
      efavirenz, emtricitabine, and tenofovir. Plasma virus loads at necropsy ranged
      from 11 to 28 copies of vRNA per ml. Viral RNA and DNA were detected during
      HAART, in tissues from numerous anatomical locations. Additional analysis
      provided evidence for full-length viral RNA in tissues of animals with virus
      suppressed by HAART. The highest levels of vDNA and vRNA in HAART-treated
      macaques were in lymphoid tissues, particularly the spleen, lymph nodes, and
      gastrointestinal tract tissues. This study is the first comprehensive analysis of
      the tissue and organ distribution of a primate AIDS virus during HAART. These
      data demonstrate widespread persistence of residual virus in tissues during
      HAART.

PMID- 20032181
TI  - Contributions of the avian influenza virus HA, NA, and M2 surface proteins to the
      induction of neutralizing antibodies and protective immunity.
AB  - Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes severe
      disease and mortality in poultry. Increased transmission of H5N1 HPAIV from birds
      to humans is a serious threat to public health. We evaluated the individual
      contributions of each of the three HPAIV surface proteins, namely, the
      hemagglutinin (HA), the neuraminidase (NA), and the M2 proteins, to the induction
      of HPAIV-neutralizing serum antibodies and protective immunity in chickens. Using
      reverse genetics, three recombinant Newcastle disease viruses (rNDVs) were
      engineered, each expressing the HA, NA, or M2 protein of H5N1 HPAIV. Chickens
      were immunized with NDVs expressing a single antigen (HA, NA, and M2), two
      antigens (HA+NA, HA+M2, and NA+M2), or three antigens (HA+NA+M2). Immunization
      with HA or NA induced high titers of HPAIV-neutralizing serum antibodies, with
      the response to HA being greater, thus identifying HA and NA as independent
      neutralization antigens. M2 did not induce a detectable neutralizing serum
      antibody response, and inclusion of M2 with HA or NA reduced the magnitude of the
      response. Immunization with HA alone or in combination with NA induced complete
      protection against HPAIV challenge. Immunization with NA alone or in combination
      with M2 did not prevent death following challenge, but extended the time period
      before death. Immunization with M2 alone had no effect on morbidity or mortality.
      Thus, there was no indication that M2 is immunogenic or protective. Furthermore,
      inclusion of NA in addition to HA in a vaccine preparation for chickens may not
      enhance the high level of protection provided by HA.

PMID- 20032182
TI  - The foamy virus genome remains unintegrated in the nuclei of G1/S phase-arrested
      cells, and integrase is critical for preintegration complex transport into the
      nucleus.
AB  - Foamy viruses are a member of the spumavirus subfamily of retroviruses with
      unique mechanisms of virus replication. Foamy virus replication is cell cycle
      dependent; however, the genome is found in the nuclei of cells arrested in the
      G(1)/S phase. Despite the presence of genome in the nuclei of growth-arrested
      cells, there is no viral gene expression, thus explaining its dependency on cell
      cycle. This report shows that the foamy virus genome remains unintegrated in
      G(1)/S phase-arrested cells. The foamy virus genome is detected by confocal
      microscopy in the nuclei of both dividing and growth-arrested cells. Alu PCR
      revealed foamy virus-specific DNA amplification from genomic DNA isolated in
      cycling cells at 24 h postinfection. In arrested cells no foamy virus DNA band
      was detected in cells harvested at 1 or 7 days after infection, and a very faint
      band that is significantly less than DNA amplified from cycling cells was
      observed at day 15. After these cells were arrested at the G(1)/S phase for 1, 7,
      or 15 days they were allowed to cycle, at which time foamy virus-specific DNA
      amplification was readily observed. Taken together, these results suggest that
      the foamy virus genome persists in nondividing cells without integrating. We have
      also established evidence for the first time that the foamy virus genome and Gag
      translocation into the nucleus are dependent on integrase in cycling cells,
      implicating the role of integrase in transport of the preintegration complex into
      the nucleus. Furthermore, despite the presence of a nuclear localization signal
      sequence in Gag, we observed no foamy virus Gag importation into the nucleus in
      the absence of integrase.

PMID- 20032183
TI  - Evidence of early B-cell dysregulation in simian immunodeficiency virus
      infection: rapid depletion of naive and memory B-cell subsets with delayed
      reconstitution of the naive B-cell population.
AB  - Despite eliciting a robust antibody response in humans, several studies in human
      immunodeficiency virus (HIV)-infected patients have demonstrated the presence of
      B-cell deficiencies during the chronic stage of infection. While several
      explanations for the HIV-induced B-cell deficit have been proposed, a clear
      mechanistic understanding of this loss of B-cell functionality is not known. This
      study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques
      to assess B-cell population dynamics beginning at the acute phase and continuing
      through the chronic phase of infection. Flow cytometric assessment demonstrated a
      significant early depletion of both naive and memory B-cell subsets in the
      peripheral blood, with differential kinetics for recovery of these populations.
      Furthermore, the altered numbers of naive and memory B-cell subsets in these
      animals corresponded with increased B-cell activation and altered proliferation
      profiles during the acute phase of infection. Finally, all animals produced high
      titers of antibody, demonstrating that the measurement of virus-specific antibody
      responses was not an accurate reflection of alterations in the B-cell
      compartment. These data indicate that dynamic B-cell population changes in SIV
      infected macaques arise very early after infection at the precise time when an
      effective adaptive immune response is needed.

PMID- 20032184
TI  - A human cytomegalovirus gO-null mutant fails to incorporate gH/gL into the virion
      envelope and is unable to enter fibroblasts and epithelial and endothelial cells.
AB  - Human cytomegalovirus (HCMV) depends upon a five-protein complex, gH/gL/UL128
      131, to enter epithelial and endothelial cells. A separate HCMV gH/gL-containing
      complex, gH/gL/gO, has been described. Our prevailing model is that gH/gL/UL128
      131 is required for entry into biologically important epithelial and endothelial
      cells and that gH/gL/gO is required for infection of fibroblasts. Genes encoding
      UL128-131 are rapidly mutated during laboratory propagation of HCMV on
      fibroblasts, apparently related to selective pressure for the fibroblast entry
      pathway. Arguing against this model in the accompanying paper by B. J. Ryckman et
      al. (J. Virol., 84:2597-2609, 2010), we describe evidence that clinical HCMV
      strain TR expresses a gO molecule that acts to promote endoplasmic reticulum (ER)
      export of gH/gL and that gO is not stably incorporated into the virus envelope.
      This was different from results involving fibroblast-adapted HCMV strain AD169,
      which incorporates gO into the virion envelope. Here, we constructed a TR gO-null
      mutant, TRDeltagO, that replicated to low titers, spread poorly among
      fibroblasts, but produced normal quantities of extracellular virus particles.
      TRDeltagO particles released from fibroblasts failed to infect fibroblasts and
      epithelial and endothelial cells, but the chemical fusogen polyethylene glycol
      (PEG) could partially overcome defects in infection. Therefore, TRDeltagO is
      defective for entry into all three cell types. Defects in entry were explained by
      observations showing that TRDeltagO incorporated about 5% of the quantities of
      gH/gL in extracellular virus particles compared with that in wild-type virions.
      Although TRDeltagO particles could not enter cells, cell-to-cell spread involving
      epithelial and endothelial cells was increased relative to TR, apparently
      resulting from increased quantities of gH/gL/UL128-131 in virions. Together, our
      data suggest that TR gO acts as a chaperone to promote ER export and the
      incorporation of gH/gL complexes into the HCMV envelope. Moreover, these data
      suggest that it is gH/gL, and not gH/gL/gO, that is present in virions and is
      required for infection of fibroblasts and epithelial and endothelial cells. Our
      observations that both gH/gL and gH/gL/UL128-131 are required for entry into
      epithelial/endothelial cells differ from models for other beta- and
      gammaherpesviruses that use one of two different gH/gL complexes to enter
      different cells.

PMID- 20032185
TI  - Downregulation of a chitin deacetylase-like protein in response to baculovirus
      infection and its application for improving baculovirus infectivity.
AB  - Several expressed sequence tags (ESTs) with homology to chitin deacetylase-like
      protein (CDA) were selected from a group of Helicoverpa armigera genes whose
      expression changed after infection with H. armigera single nucleopolyhedrovirus
      (HearNPV). Some of these ESTs coded for a midgut protein containing a chitin
      deacetylase domain (CDAD). The expressed protein, HaCDA5a, did not show chitin
      deacetylase activity, but it showed a strong affinity for binding to chitin.
      Sequence analysis showed the lack of any chitin binding domain, described for all
      currently known peritrophic membrane (PM) proteins. HaCDA5a has previously been
      detected in the H. armigera PM. Such localization, together with its
      downregulation after pathogen infection, led us to hypothesize that this protein
      might be responsible for the homeostasis of the PM structure and that, by
      reduction of its expression, the insect may reduce PM permeability, decreasing
      the entrance of baculovirus. To test this hypothesis, we constructed a
      recombinant nucleopolyhedrovirus to express HaCDA5a in insect cells and tested
      its influence on PM permeability as well as the influence of HaCDA5a expression
      on the performance of the baculovirus. The experiments showed that HaCDA5a
      increased PM permeability, in a concentration-dependent manner. Bioassays on
      Spodoptera frugiperda and Spodoptera exigua larvae revealed that NPV expressing
      HaCDA5a was more infective than its parental virus. However, no difference in
      virulence was observed when the viruses were injected intrahemocoelically. These
      findings support the downregulation of a midgut-specific CDA-like protein as a
      possible mechanism used by H. armigera to reduce susceptibility to baculovirus by
      decreasing PM permeability.

PMID- 20032186
TI  - The latent origin of replication of Epstein-Barr virus directs viral genomes to
      active regions of the nucleus.
AB  - The Epstein-Barr virus efficiently infects human B cells. The EBV genome is
      maintained extrachromosomally and replicates synchronously with the host's
      chromosomes. The latent origin of replication (oriP) guarantees plasmid stability
      by mediating two basic functions: replication and segregation of the viral
      genome. While the segregation process of EBV genomes is well understood, little
      is known about its chromatin association and nuclear distribution during
      interphase. Here, we analyzed the nuclear localization of EBV genomes and the
      role of functional oriP domains FR and DS for basic functions such as the
      transformation of primary cells, their role in targeting EBV genomes to distinct
      nuclear regions, and their association with epigenetic domains. Fluorescence in
      situ hybridization visualized the localization of extrachromosomal EBV genomes in
      the regions adjacent to chromatin-dense territories called the perichromatin.
      Further, immunofluorescence experiments demonstrated a preference of the viral
      genome for histone 3 lysine 4-trimethylated (H3K4me3) and histone 3 lysine 9
      acetylated (H3K9ac) nuclear regions. To determine the role of FR and DS for
      establishment and subnuclear localization of EBV genomes, we transformed primary
      human B lymphocytes with recombinant mini-EBV genomes containing different oriP
      mutants. The loss of DS results in a slightly increased association in H3K27me3
      domains. This study demonstrates that EBV genomes or oriP-based extrachromosomal
      vector systems are integrated into the higher order nuclear organization. We
      found that viral genomes are not randomly distributed in the nucleus. FR but not
      DS is crucial for the localization of EBV in perichromatic regions that are
      enriched for H3K4me3 and H3K9ac, which are hallmarks of transcriptionally active
      regions.

PMID- 20032187
TI  - Sequestration of free tubulin molecules by the viral protein NSP2 induces
      microtubule depolymerization during rotavirus infection.
AB  - Microtubules, components of the cell cytoskeleton, play a central role in
      cellular trafficking. Here we show that rotavirus infection leads to a remodeling
      of the microtubule network together with the formation of tubulin granules. While
      most microtubules surrounding the nucleus depolymerize, others appear packed at
      the cell periphery. In microtubule depolymerization areas, tubulin granules are
      observed; they colocalize with viroplasms, viral compartments formed by
      interactions between rotavirus proteins NSP2 and NSP5. With purified proteins, we
      show that tubulin directly interacts in vitro with NSP2 but not with NSP5. The
      binding of NSP2 to tubulin is independent of its phosphatase activity. The
      comparison of three-dimensional (3-D) reconstructions of NSP2 octamers alone or
      associated with tubulin reveals electron densities in the positively charged
      grooves of NSP2 that we attribute to tubulin. Site-directed mutagenesis of NSP2
      and competition assays between RNA and tubulin for NSP2 binding confirm that
      tubulin binds to these charged grooves of NSP2. Although the tubulin position
      within NSP2 grooves cannot be precisely determined, the tubulin C-terminal H12
      alpha-helix could be involved in the interaction. NSP2 overexpression and
      rotavirus infection produce similar effects on the microtubule network. NSP2
      depolymerizes microtubules and leads to tubulin granule formation. Our results
      demonstrate that tubulin is a viroplasm component and reveal an original
      mechanism. Tubulin sequestration by NSP2 induces microtubule depolymerization.
      This depolymerization probably reroutes the cell machinery by inhibiting
      trafficking and functions potentially involved in defenses to viral infections.

PMID- 20032188
TI  - The interferon stimulator mitochondrial antiviral signaling protein facilitates
      cell death by disrupting the mitochondrial membrane potential and by activating
      caspases.
AB  - Interferon (IFN) signaling is initiated by the recognition of viral components by
      host pattern recognition receptors. Dengue virus (DEN) triggers IFN-beta
      induction through a molecular mechanism involving the cellular RIG-I/MAVS
      signaling pathway. Here we report that the MAVS protein level is reduced in DEN
      infected cells and that caspase-1 and caspase-3 cleave MAVS at residue D429. In
      addition to its well-known function in IFN induction, MAVS is also a proapoptotic
      molecule that triggers disruption of the mitochondrial membrane potential and
      activation of caspases. Although different domains are required for the induction
      of cytotoxicity and IFN, caspase cleavage at residue 429 abolished both functions
      of MAVS. The apoptotic role of MAVS in viral infection and double-stranded RNA
      (dsRNA) stimulation was demonstrated in cells with reduced endogenous MAVS
      expression induced by RNA interference. Even though IFN-beta promoter activation
      was largely suppressed, DEN production was not affected greatly in MAVS knockdown
      cells. Instead, DEN- and dsRNA-induced cell death and caspase activation were
      delayed and attenuated in the cells with reduced levels of MAVS. These results
      reveal a new role of MAVS in the regulation of cell death beyond its well-known
      function of IFN induction in antiviral innate immunity.

PMID- 20032189
TI  - Conserved motifs within Ebola and Marburg virus VP40 proteins are important for
      stability, localization, and subsequent budding of virus-like particles.
AB  - The filovirus VP40 protein is capable of budding from mammalian cells in the form
      of virus-like particles (VLPs) that are morphologically indistinguishable from
      infectious virions. Ebola virus VP40 (eVP40) contains well-characterized
      overlapping L domains, which play a key role in mediating efficient virus egress.
      L domains represent only one component required for efficient budding and,
      therefore, there is a need to identify and characterize additional domains
      important for VP40 function. We demonstrate here that the (96)LPLGVA(101)
      sequence of eVP40 and the corresponding (84)LPLGIM(89) sequence of Marburg virus
      VP40 (mVP40) are critical for efficient release of VP40 VLPs. Indeed, deletion of
      these motifs essentially abolished the ability of eVP40 and mVP40 to bud as VLPs.
      To address the mechanism by which the (96)LPLGVA(101) motif of eVP40 contributes
      to egress, a series of point mutations were introduced into this motif. These
      mutants were then compared to the eVP40 wild type in a VLP budding assay to
      assess budding competency. Confocal microscopy and gel filtration analyses were
      performed to assess their pattern of intracellular localization and ability to
      oligomerize, respectively. Our results show that mutations disrupting the
      (96)LPLGVA(101) motif resulted in both altered patterns of intracellular
      localization and self-assembly compared to wild-type controls. Interestingly,
      coexpression of either Ebola virus GP-WT or mVP40-WT with eVP40-DeltaLPLGVA
      failed to rescue the budding defective eVP40-DeltaLPLGVA mutant into VLPs;
      however, coexpression of eVP40-WT with mVP40-DeltaLPLGIM successfully rescued
      budding of mVP40-DeltaLPLGIM into VLPs at mVP40-WT levels. In sum, our findings
      implicate the LPLGVA and LPLGIM motifs of eVP40 and mVP40, respectively, as being
      important for VP40 structure/stability and budding.

PMID- 20032190
TI  - Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein
      griffithsin against emerging viruses of the family Coronaviridae.
AB  - Viruses of the family Coronaviridae have recently emerged through zoonotic
      transmission to become serious human pathogens. The pathogenic agent responsible
      for severe acute respiratory syndrome (SARS), the SARS coronavirus (SARS-CoV), is
      a member of this large family of positive-strand RNA viruses that cause a
      spectrum of disease in humans, other mammals, and birds. Since the publicized
      outbreaks of SARS in China and Canada in 2002-2003, significant efforts
      successfully identified the causative agent, host cell receptor(s), and many of
      the pathogenic mechanisms underlying SARS. With this greater understanding of
      SARS-CoV biology, many researchers have sought to identify agents for the
      treatment of SARS. Here we report the utility of the potent antiviral protein
      griffithsin (GRFT) in the prevention of SARS-CoV infection both in vitro and in
      vivo. We also show that GRFT specifically binds to the SARS-CoV spike
      glycoprotein and inhibits viral entry. In addition, we report the activity of
      GRFT against a variety of additional coronaviruses that infect humans, other
      mammals, and birds. Finally, we show that GRFT treatment has a positive effect on
      morbidity and mortality in a lethal infection model using a mouse-adapted SARS
      CoV and also specifically inhibits deleterious aspects of the host immunological
      response to SARS infection in mammals.

PMID- 20032191
TI  - Human leukocyte antigen class I supertypes and HIV-1 control in African
      Americans.
AB  - The role of human leukocyte antigen (HLA) class I supertypes in controlling human
      immunodeficiency virus type 1 (HIV-1) infection in African Americans has not been
      established. We examined the effects of the HLA-A and HLA-B alleles and
      supertypes on the outcomes of HIV-1 clade B infection among 338 African American
      women and adolescents. HLA-B58 and -B62 supertypes (B58s and B62s) were
      associated with favorable HIV-1 disease control (proportional odds ratio [POR] of
      0.33 and 95% confidence interval [95% CI] of 0.21 to 0.52 for the former and POR
      of 0.26 and 95% CI of 0.09 to 0.73 for the latter); B7s and B44s were associated
      with unfavorable disease control (POR of 2.39 and 95% CI of 1.54 to 3.73 for the
      former and POR of 1.63 and 95% CI of 1.08 to 2.47 for the latter). In general,
      individual alleles within specific B supertypes exerted relatively homogeneous
      effects. A notable exception was B27s, whose protective influence (POR, 0.58; 95%
      CI, 0.35 to 0.94) was masked by the opposing effect of its member allele B*1510.
      The associations of most B supertypes (e.g., B58s and B7s) were largely explained
      either by well-known effects of constituent B alleles or by effects of previously
      unimplicated B alleles aggregated into a particular supertype (e.g., B44s and
      B62s). A higher frequency of HLA-B genotypic supertypes correlated with a higher
      mean viral load (VL) and lower mean CD4 count (Pearson's r = 0.63 and 0.62,
      respectively; P = 0.03). Among the genotypic supertypes, B58s and its member
      allele B*57 contributed disproportionately to the explainable VL variation. The
      study demonstrated the dominant role of HLA-B supertypes in HIV-1 clade B
      infected African Americans and further dissected the contributions of individual
      class I alleles and their population frequencies to the supertype effects.

PMID- 20032192
TI  - Discovery of 2-aminothiazoles as potent antiprion compounds.
AB  - Prion diseases are fatal, untreatable neurodegenerative diseases caused by the
      accumulation of the misfolded, infectious isoform of the prion protein (PrP),
      termed PrP(Sc). In an effort to identify novel inhibitors of prion formation, we
      utilized a high-throughput enzyme-linked immunosorbent assay (ELISA) to evaluate
      PrP(Sc) reduction in prion-infected neuroblastoma cell lines (ScN2a). We screened
      a library of approximately 10,000 diverse small molecules in 96-well format and
      identified 121 compounds that reduced PrP(Sc) levels at a concentration of 5
      microM. Four chemical scaffolds were identified as potential candidates for
      chemical optimization based on the presence of preliminary structure-activity
      relationships (SAR) derived from the primary screening data. A follow-up analysis
      of a group of commercially available 2-aminothiazoles showed this class as
      generally active in ScN2a cells. Our results establish 2-aminothiazoles as
      promising candidates for efficacy studies of animals and validate our drug
      discovery platform as a viable strategy for the identification of novel lead
      compounds with antiprion properties.

PMID- 20032193
TI  - Human cytomegalovirus TR strain glycoprotein O acts as a chaperone promoting
      gH/gL incorporation into virions but is not present in virions.
AB  - Human cytomegalovirus (HCMV) produces the following two gH/gL complexes: gH/gL/gO
      and gH/gL/UL128-131. Entry into epithelial and endothelial cells requires
      gH/gL/UL128-131, and we have provided evidence that gH/gL/UL128-131 binds
      saturable epithelial cell receptors to mediate entry. HCMV does not require
      gH/gL/UL128-131 to enter fibroblasts, and laboratory adaptation to fibroblasts
      results in mutations in the UL128-131 genes, abolishing infection of epithelial
      and endothelial cells. HCMV gO-null mutants produce very small plaques on
      fibroblasts yet can spread on endothelial cells. Thus, one prevailing model
      suggests that gH/gL/gO mediates infection of fibroblasts, while gH/gL/UL128-131
      mediates entry into epithelial/endothelial cells. Most biochemical studies of gO
      have involved the HCMV lab strain AD169, which does not assemble gH/gL/UL128-131
      complexes. We examined gO produced by the low-passage clinical HCMV strain TR.
      Surprisingly, TR gO was not detected in purified extracellular virus particles.
      In TR-infected cells, gO remained sensitive to endoglycosidase H, suggesting that
      the protein was not exported from the endoplasmic reticulum (ER). However, TR gO
      interacted with gH/gL in the ER and promoted export of gH/gL from the ER to the
      Golgi apparatus. Pulse-chase experiments showed that a fraction of gO remained
      bound to gH/gL for relatively long periods, but gO eventually dissociated or was
      degraded and was not found in extracellular virions or secreted from cells. The
      accompanying report by P. T. Wille et al. (J. Virol., 84:2585-2596, 2010) showed
      that a TR gO-null mutant failed to incorporate gH/gL into virions and that the
      mutant was unable to enter fibroblasts and epithelial and endothelial cells. We
      concluded that gO acts as a molecular chaperone, increasing gH/gL ER export and
      incorporation into virions. It appears that gO competes with UL128-131 for
      binding onto gH/gL but is released from gH/gL, so that gH/gL (lacking UL128-131)
      is incorporated into virions. Thus, our revised model suggests that both gH/gL
      and gH/gL/UL128-131 are required for entry into epithelial and endothelial cells.

PMID- 20032194
TI  - Species differences in the formation of vabicaserin carbamoyl glucuronide.
AB  - Vabicaserin is a potent 5-hydroxtryptamine 2C full agonist with therapeutic
      potential for a wide array of psychiatric disorders. Metabolite profiles
      indicated that vabicaserin was extensively metabolized via carbamoyl
      glucuronidation after oral administration in humans. In the present study, the
      differences in the extent of vabicaserin carbamoyl glucuronide (CG) formation in
      humans and in animals used for safety assessment were investigated. After oral
      dosing, the systemic exposure ratios of CG to vabicaserin were approximately 12
      and up to 29 in monkeys and humans, respectively, and the ratios of CG to
      vabicaserin were approximately 1.5 and 1.7 in mice and dogs, respectively. These
      differences in systemic levels of CG are likely related to species differences in
      the rate and extent of CG formation and elimination. Whereas CG was the
      predominant circulating metabolite in humans and a major metabolite in mice,
      dogs, and monkeys, it was a relatively minor metabolite in rats, in which
      oxidative metabolism was the major metabolic pathway. Although the CG was not
      detected in plasma or urine of rats, approximately 5% of the dose was excreted in
      bile as CG in the 24-h collection postdose, indicating the rat had the metabolic
      capability of producing the CG. In vitro, in a CO(2)-enriched environment, the CG
      was the predominant metabolite in dog and human liver microsomes, a major
      metabolite in monkey and mice, and only a very minor metabolite in rats.
      Carbamoyl glucuronidation and hydroxylation had similar contributions to
      vabicaserin metabolism in mouse and monkey liver microsomes. However, only trace
      amounts of CG were formed in rat liver microsomes, and other metabolites were
      more prominent than the CG. In conclusion, significant differences in the extent
      of formation of the CG were observed among the various species examined. The
      exposure ratios of CG to vabicaserin were highest in humans, followed by monkeys,
      then mice and dogs, and lowest in rats, and the in vitro metabolite profiles
      generally correlated well with the in vivo metabolites.

PMID- 20032195
TI  - Activation of the aryl-hydrocarbon receptor inhibits invasive and metastatic
      features of human breast cancer cells and promotes breast cancer cell
      differentiation.
AB  - The current statistics associated with breast cancer continue to show a
      relatively high recurrence rate together with a poor survival for aggressive
      metastatic disease. These findings reflect, in part, the pharmaceutical
      intractability of processes involved in the metastatic process and highlight the
      need to identify additional drug targets for the treatment of late-stage disease.
      In the current study, we report that ligand activation of the aryl-hydrocarbon
      receptor (AhR) inhibits multiple aspects of the metastatic process in a panel of
      breast cancer cell lines that represent the major breast cancer subtypes.
      Specifically, it was observed that treatment with exogenous AhR agonists
      significantly inhibited cell invasiveness and motility in the Boyden chamber
      assay and inhibited colony formation in soft agar regardless of estrogen receptor
      (ER), progesterone receptor, or human epidermal growth factor receptor 2 status.
      Knockdown of the AhR using small interfering RNA duplexes demonstrated that the
      inhibition of invasiveness was receptor dependent and that endogenous receptor
      activity was protective in each cell type examined. The inhibition of
      invasiveness and anchorage-independent growth correlated with the ability of
      exogenous AhR agonists to promote differentiation. Finally, exogenous AhR
      agonists were able to promote differentiation in a putative mammary cancer stem
      cell line. Cumulatively, these results suggest that the AhR plays an important
      role in mammary epithelial differentiation and, as such, represent a promising
      therapeutic target for a range of phenotypically distinct human breast cancers.

PMID- 20032196
TI  - Regulation of signal transducer and activator of transcription 3 enhanceosome
      formation by apurinic/apyrimidinic endonuclease 1 in hepatic acute phase
      response.
AB  - The signal transducer and activator of transcription-3 (STAT3) is a latent IL-6
      inducible transcription factor that mediates hepatic and vascular inflammation.
      In this study, we make the novel observation that STAT3 forms an inducible
      complex with the apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector
      factor-1 (APE1/Ref-1), an essential multifunctional protein in DNA base excision
      repair, and studied the role of APE1/Ref-1 in STAT3 function. Using a
      transfection-coimmunoprecipitation assay, we observed that APE1 selectively binds
      the NH(2)-terminal acetylation domain of STAT3. Ectopic expression of APE1
      potentiated inducible STAT3 reporter activity, whereas knockdown of APE1 resulted
      in reduced IL-6-inducible acute-phase reactant protein expression (C-reactive
      protein and serum amyloid P) and monocyte chemotactic protein-1 expression. The
      mechanism for APE1 requirement in IL-6 signaling was indicated by reduced STAT3
      DNA binding activity observed in response to small interfering RNA-mediated APE1
      silencing. Consistent with these in vitro studies, we also observed that
      lipopolysaccharide-induced activation of acute-phase reactant protein expression
      is significantly abrogated in APE1 heterozygous mice compared with wild-type
      mice. IL-6 induces both STAT3 and APE1 to bind the suppressor of cytokine
      signaling-3 and gamma-fibrionogen promoters in their native chromatin
      environment. Moreover, we observed that APE1 knockdown destabilized formation of
      the STAT3-inducible enhanceosome on the endogenous gamma-fibrionogen promoter.
      Taken together, our study indicates that IL-6 induces a novel STAT3-APE1 complex,
      whose interaction is required for stable chromatin association in the IL-6
      induced hepatic acute phase response.

PMID- 20032197
TI  - Thyroid hormone antagonizes tumor necrosis factor-alpha signaling in pituitary
      cells through the induction of dual specificity phosphatase 1.
AB  - Pituitary function has been shown to be regulated by an increasing number of
      factors, including cytokines and hormones, such as TNFalpha and T(3). Both the
      proinflammatory cytokine TNFalpha and T(3) have been suggested to be involved in
      the maintenance of tissue homeostasis in the anterior pituitary gland. In this
      report we show that T(3) negatively interferes with MAPK p38 and nuclear factor
      kappaB (NF-kappaB) activation by TNFalpha in GH4C1 cells. Our data demonstrate
      that MAPK p38 is specifically activated upon exposure to TNFalpha and that T(3)
      abolishes this activation in a time-dependent manner by a mechanism that involves
      the induction of the MAPK phosphatase, DUSP1. Our data show that the pool of up
      regulated DUSP1 by T(3) is mainly localized to the cytosol, and that TNFalpha
      does not affect this localization. On the other hand, we show that T(3) impairs
      the activation of the NF-kappaB pathway induced by TNFalpha, producing a
      significant decrease in NF-kappaB-dependent transcription, phosphorylation of
      IkappaBalpha, translocation of p65/NF-kappaB to the nucleus, and p65/NF-kappaB
      transactivation potential. Interestingly, the overexpression of DUSP1 inhibits
      the NF-kappaB activation achieved by either TNFalpha or ectopic expression of the
      upstream inducer of MAPK p38. Conversely, DUSP1 depletion abrogates the
      inhibitory effect of T(3) on the induction of NF-kappaB-dependent transcription
      by TNFalpha. Overall, our results indicate that T(3) antagonizes TNFalpha
      signaling in rat pituitary tumor cells through the induction of DUSP1.

PMID- 20032198
TI  - The calcium-sensing receptor couples to Galpha(s) and regulates PTHrP and ACTH
      secretion in pituitary cells.
AB  - The calcium-sensing receptor (CaR or CASR as listed in the MGI Database) is a G
      protein-coupled receptor that binds and signals in response to extracellular
      calcium and other polycations. It is highly expressed on parathyroid and kidney
      cells, where it participates in the regulation of systemic calcium homeostasis.
      It is also expressed on many other cell types and is involved in a wide array of
      biological functions such as cell growth and differentiation, ion transport, and
      hormone secretion. It has been described to couple to several different G
      proteins including Galpha(i/0), Galpha(q/11), and Galpha(12/13). Recently, it has
      also been shown to stimulate cAMP production by coupling to Galpha(s) in
      immortalized or malignant breast cells. The CaR is expressed on cells in the
      anterior pituitary and had previously been described to stimulate cAMP production
      in these cells. In this report, we examined signaling from the CaR in murine
      pituitary corticotroph-derived, AtT-20 cells. We found that CaR activation led to
      the stimulation of cAMP production, and PTH-related protein (PTHrP or PTHLH as
      listed in the MGI Database) and ACTH secretion from these cells. Furthermore,
      manipulation of cAMP levels was able to modulate PTHrP and ACTH secretion
      independent of changes in extracellular calcium. Finally, we demonstrated that
      the CaR couples to Galpha(s) in AtT-20 cells. Therefore, in pituitary
      corticotroph-like cells, as in breast cancer cells, the CaR utilizes Galpha(s)
      and activates cAMP production to stimulate hormone secretion.

PMID- 20032199
TI  - GH modulates hepatic epidermal growth factor signaling in the mouse.
AB  - Epidermal growth factor (EGF) is a key regulator of cell survival and
      proliferation involved in the pathogenesis and progression of different types of
      cancer. The EGF receptor (EGFR) is activated by binding of the specific ligand
      but also by transactivation triggered by different growth factors including GH.
      Chronically, elevated GH levels have been associated with the progression of
      hepatocellular carcinoma. Considering EGF and GH involvement in cell
      proliferation and their signaling crosstalk, the objective of the present study
      was to analyze GH modulatory effects on EGF signaling in liver. For this purpose,
      GH receptor-knockout (GHR-KO) and GH-overexpressing transgenic mice were used.
      EGFR content was significantly decreased in GHR-KO mice. Consequently, EGF
      induced phosphorylation of EGFR, AKT, ERK1/2, STAT3, and STAT5 was significantly
      decreased in these mice. In contrast, EGFR content as well as its basal tyrosine
      phosphorylation was increased in transgenic mice overexpressing GH. However, EGF
      stimulation caused similar levels of EGFR, AKT, and ERK1/2 phosphorylation in
      normal and transgenic mice, while EGF induction of STAT3 and STAT5
      phosphorylation was inhibited in the transgenic mice. Desensitization of the
      STATs was related to decreased association of these proteins to the EGFR and
      increased association between STAT5 and the tyrosine phosphatase SH2-containing
      phosphatase-2. While GHR knockout is associated with diminished expression of the
      EGFR and a concomitant decrease in EGF signaling, GH overexpression results in
      EGFR overexpression with different effects depending on the signaling pathway
      analyzed: AKT and ERK1/2 pathways are induced by EGF, while STAT3 and STAT5
      activation is heterologously desensitized.

PMID- 20032201
TI  - Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship
      to glycaemic state.
AB  - The protein nucleobindin-2 (NUCB2, also known as nesfatin) was recently
      implicated as a mediator of anorexia and catabolism in the central nervous
      system, and has been suggested to act as a cleaved and secreted messenger. Given
      the overlap of signalling molecules between the brain and pancreas, we have
      explored the presence of NUCB2 in the islets of Langerhans. We also performed an
      investigation of the dynamic regulation of pancreatic NUCB2 in different
      metabolic states. NUCB2-like immunoreactivity was detected by immunofluorescence
      in all human and rat islet beta-cells (as detected by co-localization with
      insulin), but not in other islet cells or in the exocrine pancreas. Islet NUCB2
      content, as measured by enzyme immunoassay, did not change significantly
      following an overnight fast, but was substantially lower in islets isolated from
      an animal model of type 2 diabetes, the Goto-Kakizaki (GK) rats (48% of non
      diabetic Wistar rat control). Serum levels, however, were not different between
      Wistar and GK rats. The release of NUCB2 from isolated rat islets was
      significantly elevated following glucose challenge (123%), but this effect was
      substantially lower than that observed for insulin (816%). In contrast, serum
      levels of NUCB2 showed a reversible decrease in an i.p. glucose tolerance test.
      These data suggest a role for NUCB2 in beta-cell function and a potential
      involvement in diabetic pathology. However, our findings, together with previous
      reports, appear more compatible with intracellular actions rather than with
      endocrine/paracrine communication, and suggest that NUCB2 in serum derives
      primarily from non-islet sources.

PMID- 20032200
TI  - A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced
      growth, low bone mass and impaired adipogenesis.
AB  - A spontaneous mouse mutant, designated 'small' (sml), was recognized by reduced
      body size suggesting a defect in the IGF1/GH axis. The mutation was mapped to the
      chromosome 1 region containing Irs1, a viable candidate gene whose sequence
      revealed a single nucleotide deletion resulting in a premature stop codon.
      Despite normal mRNA levels in mutant and control littermate livers, western blot
      analysis revealed no detectable protein in mutant liver lysates. When compared
      with the control littermates, Irs1(sml)/Irs1(sml) (Irs1(sml/sml)) mice were
      small, lean, hearing impaired; had 20% less serum IGF1; were hyperinsulinemic;
      and were mildly insulin resistant. Irs1(sml/sml) mice had low bone mineral
      density, reduced trabecular and cortical thicknesses, and low bone formation
      rates, while osteoblast and osteoclast numbers were increased in the females but
      not different in the males compared with the Irs1(+/+) controls. In vitro,
      Irs1(sml/sml) bone marrow stromal cell cultures showed decreased alkaline
      phosphatase-positive colony forming units (pre-osteoblasts; CFU-AP+) and normal
      numbers of tartrate-resistant acid phosphatase-positive osteoclasts.
      Irs1(sml/sml) stromal cells treated with IGF1 exhibited a 50% decrease in AKT
      phosphorylation, indicative of defective downstream signaling. Similarities
      between engineered knockouts and the spontaneous mutation of Irs1(sml) were
      identified as well as significant differences with respect to heterozygosity and
      gender. In sum, we have identified a spontaneous mutation in the Irs1 gene
      associated with a major skeletal phenotype. Changes in the heterozygous
      Irs1(+)(/sml) mice raise the possibility that similar mutations in humans are
      associated with short stature or osteoporosis.

PMID- 20032203
TI  - Autographa californica multiple nucleopolyhedrovirus ODV-E56 envelope protein is
      required for oral infectivity and can be substituted functionally by Rachiplusia
      ou multiple nucleopolyhedrovirus ODV-E56.
AB  - The Autographa californica multiple nucleopolyhedrovirus (AcMNPV) odv-e56 gene
      encodes an occlusion-derived virus (ODV)-specific envelope protein, ODV-E56. In a
      previous analysis, the odv-e56 gene was found to be under positive selection
      pressure, suggesting that it may be a determinant of virus host range. To assess
      the role of ODV-E56 in oral infectivity and host range, we constructed
      recombinant AcMNPV clones (Ac69GFP-e56lacZ and AcIEGFP-e56lacZ) in which ODV-E56
      protein synthesis was eliminated by inserting a beta-galactosidase (lacZ)
      expression cassette into the odv-e56 open reading frame. We also constructed a
      recombinant virus, Ac69GFP-Roe56, in which the native AcMNPV odv-e56 coding
      sequence was replaced with that of Rachiplusia ou multiple nucleopolyhedrovirus
      (RoMNPV), a closely related virus that is significantly more virulent towards
      some host species than AcMNPV. The odv-e56 recombinant viruses exhibited no
      alterations in polyhedron production and morphogenesis or in the production of
      infectious budded virus in cell culture. In bioassays using three lepidopteran
      host species, the oral infectivities of the odv-e56 mutant viruses Ac69GFP
      e56lacZ and AcIEGFP-e56lacZ were profoundly impaired compared with those of wild
      type and control recombinant viruses. Oral infectivity was restored fully by
      marker rescue of the odv-e56 mutant viruses with either the AcMNPV or the RoMNPV
      odv-e56 gene. In bioassays using two host species that are more susceptible to
      RoMNPV than to AcMNPV, Ac69GFP-Roe56 killed larvae with LC50 values similar to
      those of recombinant viruses expressing AcMNPV ODV-E56. This result indicated
      that replacement of the AcMNPV odv-e56 gene with the RoMNPV orthologue did not
      increase virulence against these two species.

PMID- 20032202
TI  - Seventy-five percent nephrectomy and the disposition of inorganic mercury in 2,3
      dimercaptopropanesulfonic acid-treated rats lacking functional multidrug
      resistance protein 2.
AB  - In the present study, we evaluated the disposition of inorganic mercury (Hg(2+))
      in sham-operated and 75% nephrectomized (NPX) Wistar and transport-deficient (TR(
      )) rats treated with saline or the chelating agent meso-2,3-dimercaptosuccinic
      acid (DMSA). Based on previous studies, DMSA and TR(-) rats were used as tools to
      examine the potential role of multidrug-resistance protein 2 (MRP2) in the
      disposition of Hg(2+) during renal insufficiency. All animals were treated with a
      low dose (0.5 mumol/kg i.v.) of mercuric chloride (HgCl(2)). At 24 and 28 h after
      exposure to HgCl(2), matched groups of Wistar and TR(-) rats received normal
      saline or DMSA (intraperitoneally). Forty-eight hours after exposure to HgCl(2),
      the disposition of Hg(2+) was examined. A particularly notable effect of 75%
      nephrectomy in both strains of rats was enhanced renal accumulation of Hg(2+),
      specifically in the outer stripe of the outer medulla. In addition, hepatic
      accumulation, fecal excretion, and blood levels of Hg(2+) were enhanced in rats
      after 75% nephrectomy, especially in the TR(-) rats. Treatment with DMSA
      increased both the renal tubular elimination and urinary excretion of Hg(2+) in
      all rats. DMSA did not, however, affect hepatic content of Hg(2+), even in the
      75% NPX TR(-) rats. We also show with real-time polymerase chain reaction that
      after 75% nephrectomy and compensatory renal growth, expression of MRP2 (only in
      Wistar rats) and organic anion transporter 1 is enhanced in the remaining
      functional proximal tubules. We conclude that MRP2 plays a significant role in
      the renal and corporal disposition of Hg(2+) after a 75% reduction of renal mass.

PMID- 20032204
TI  - Host factor pleiotrophin induces human immunodeficiency virus type 1 replication
      associated with inflammatory cytokine expression.
AB  - Pleiotrophin (PTN) is a polypeptide that belongs to a family of heparin-binding
      growth factors; it displays mitogenic activity for a wide variety of cells. In a
      previous study, we reported that PTN induces the stimulation of expression of
      inflammatory cytokines, including tumour necrosis factor alpha (TNF-alpha),
      interleukin (IL)-1beta and IL-6, in quiescent human peripheral blood mononuclear
      cells (PBMCs) through B-lymphocyte binding. These results emphasize the
      importance of PTN in the regulation of inflammatory processes. Moreover, using in
      vitro infection of PBMCs or using PBMCs from AIDS patients, we showed that PTN
      was sufficient to induce human immunodeficiency virus type 1 (HIV-1) replication.
      Moreover, neutralization of TNF-alpha, IL-1beta and IL-6 suppressed HIV
      replication in PTN-stimulated PBMCs. As these cytokines are potent upregulators
      of virus expression, these results should prove useful in investigating the role
      of PTN as a host factor in the regulation of pathological disorders in HIV-1
      infection. Identification of this host factor could be important for
      understanding HIV disease and designating therapeutic approaches.

PMID- 20032205
TI  - Dendritic cells are susceptible to infection with wild-type adenovirus, inducing
      a differentiation arrest in precursor cells and inducing a strong T-cell
      stimulation.
AB  - Adenovirus infection after stem cell transplantation is a significant cause of
      morbidity and mortality, especially in children. A robust T-cell response induced
      by dendritic cells (DC) is crucial for clearing the virus, suggesting their
      pivotal role for the response to human adenoviruses (HAdV). Despite the
      widespread use of adenoviral vectors, the properties and kinetics of HAdV
      infection of DC have not been addressed yet. We show that a recent clinical HAdV,
      subgenus C/serotype 2 (strain BB2000-61), infects cells of the myeloid lineage.
      Infected DC produce early and late viral antigens and show an altered expression
      of surface markers. Infection of monocytes renders them refractory to
      differentiation into DC. Additionally, HAdV-infected DC are strong stimulators of
      CD8+ T cells. In summary, HAdV seems to manipulate the immune response by
      infection of DC and possibly uses the infection of monocytes as a means to escape
      recognition by T cells.

PMID- 20032206
TI  - Replicative intermediates of maize streak virus found during leaf development.
AB  - Geminiviruses of the genera Begomovirus and Curtovirus utilize three replication
      modes: complementary-strand replication (CSR), rolling-circle replication (RCR)
      and recombination-dependent replication (RDR). Using two-dimensional gel
      electrophoresis, we now show for the first time that maize streak virus (MSV),
      the type member of the most divergent geminivirus genus, Mastrevirus, does the
      same. Although mastreviruses have fewer regulatory genes than other geminiviruses
      and uniquely express their replication-associated protein (Rep) from a spliced
      transcript, the replicative intermediates of CSR, RCR and RDR could be detected
      unequivocally within infected maize tissues. All replicative intermediates
      accumulated early and, to varying degrees, were already present in the shoot apex
      and leaves at different maturation stages. Relative to other replicative
      intermediates, those associated with RCR increased in prevalence during leaf
      maturation. Interestingly, in addition to RCR-associated DNA forms seen in other
      geminiviruses, MSV also apparently uses dimeric open circular DNA as a template
      for RCR.

PMID- 20032207
TI  - Human immunodeficiency virus type 1 evasion of a neutralizing anti-V3 antibody
      involves acquisition of a potential glycosylation site in V2.
AB  - It has been reported that the addition of a potential N-linked glycosylation site
      (PNGS) to the gp120 human immunodeficiency virus type 1 (HIV-1) envelope
      glycoprotein provides protection against neutralizing antibodies (NAbs) by acting
      as a 'glycan shield'. In this study, we induced insertion of a PNGS into the V2
      region of HIV-1(BaL) with the KD-247 anti-V3 neutralizing monoclonal antibody. In
      the presence of KD-247 (200 microg ml(-1)) at passage five, viruses with 3 aa
      mutations in the C2 (T240S and I283T) and V3 (T319A) regions expanded from pre
      existing variants. After six passages with KD-247 (>300 microg ml(-1)), a PNGS
      emerged in the V2 region in addition to C2 (T240S) and V3 mutations (R315K and
      F317L). A variant with a PNGS insertion in V2, but no V3 mutations was sensitive
      to KD-247, whereas a clone with a V2 PNGS insertion and mutations in V3
      demonstrated a high level of resistance to KD-247. Replication kinetic analysis
      revealed that the F317L mutation in V3 played a compensatory role for fitness
      loss caused by the PNGS insertion in V2. The evading HIV-1 variant did not revert
      back to the wild-type virus after 14 passages without KD-247. These findings
      demonstrate that the virus with fitness-loss mutations can replicate equally as
      well as the wild-type virus to acquire some key mutations in the V3 stem and the
      C2 region, and the compensated variants containing PNGS do not revert back to the
      ancestral virus even in the absence of NAb.

PMID- 20032208
TI  - Characterization of receptor proteins using affinity cross-linking with
      biotinylated ligands.
AB  - The plant genome encodes a wide range of receptor-like proteins but the function
      of most of these proteins is unknown. We propose the use of affinity cross
      linking of biotinylated ligands for a ligand-based survey of the corresponding
      receptor molecules. Biotinylated ligands not only enable the analysis of receptor
      ligand interactions without the use of radioactive compounds but also the
      isolation and identification of receptor molecules by a simple affinity trapping
      method. We successfully applied this method for the characterization, isolation
      and identification of the chitin elicitor binding protein (CEBiP). A biocytin
      hydrazide conjugate of N-acetylchitooctaose (GN8-Bio) was synthesized and used
      for the detection of CEBiP in the plasma or microsomal membrane preparations from
      rice and carrot cells. Binding characteristics of CEBiP analyzed by inhibition
      studies were in good agreement with the previous results obtained with the use of
      a radiolabeled ligand. The biotin-tagged CEBiP could be purified by avidin
      affinity chromatography and identified by LC-MALDI-MS/MS after tryptic digestion.
      We also used this method to detect OsFLS2, a rice receptor-like kinase for the
      perception of the peptide elicitor flg22, in membrane preparations from rice
      cells overexpressing OsFLS2. This work demonstrates the applicability of this
      method to the purification and identification of plant receptor proteins.

PMID- 20032209
TI  - A non-genomic signaling pathway shut down by mating changes the estradiol-induced
      gene expression profile in the rat oviduct.
AB  - Estradiol (E(2)) accelerates oviductal egg transport through intraoviductal non
      genomic pathways in unmated rats and through genomic pathways in mated rats. This
      shift in pathways has been designated as intracellular path shifting (IPS), and
      represents a novel and hitherto unrecognized effect of mating on the female
      reproductive tract. We had reported previously that IPS involves shutting down
      the E(2) non-genomic pathway up- and downstream of 2-methoxyestradiol. Here, we
      evaluated whether IPS involves changes in the genomic pathway too. Using
      microarray analysis, we found that a common group of genes changed its expression
      in response to E(2) in unmated and mated rats, indicating that an E(2) genomic
      signaling pathway is present before and after mating; however, a group of genes
      decreased its expression only in mated rats and another group of genes increased
      its expression only in unmated rats. We evaluated the possibility that this
      difference is a consequence of an E(2) non-genomic signaling pathway present in
      unmated rats, but not in mated rats. Mating shuts down this E(2) non-genomic
      signaling pathway up- and downstream of cAMP production. The Star level is
      increased by E(2) in unmated rats, but not in mated rats. This is blocked by the
      antagonist of estrogen receptor ICI 182 780, the adenylyl cyclase inhibitor SQ
      22536, and the catechol-O-methyltransferase inhibitor, OR 486. These results
      indicate that the E(2)-induced gene expression profile in the rat oviduct differs
      before and after mating, and this difference is probably mediated by an E(2) non
      genomic signaling pathway operating on gene expression only in unmated rats.

PMID- 20032210
TI  - Influence of leptin on in vitro maturation and steroidogenic secretion of cumulus
      oocyte complexes through JAK2/STAT3 and MEK 1/2 pathways in the rabbit model.
AB  - Extreme body mass indexes may impair reproductive outcome in assisted
      reproductive technologies. Leptin reflects the amount of body fat and could act
      as a modulator of oocyte quality through activation of specific transcription
      factors. The aim of this work was to establish whether: 1) leptin influences
      meiotic and cytoplasmic oocyte maturation; 2) STAT3 and MAPK mediate the effects
      of leptin and 3) leptin modulates steroid secretion by cumulus-oocyte complexes
      (COC) during in vitro maturation (IVM). We confirmed immunolocalisation of leptin
      receptor in oocytes, cumulus/granulosa cells during the peri-ovulatory period.
      The confocal study showed that COC supplemented with 1, 10 and 100 ng/ml leptin
      had a significantly higher metaphase II (MII) percentage than those IVM without
      leptin (P<0.05) and a similar MII index compared to the group supplemented with
      10% FCS. Leptin did not increase the percentage of cytoplasmically matured
      oocytes in terms of cortical granule migration rate, whereas a significantly
      higher index was found in the FCS group (P<0.001). Oestradiol concentrations in
      spent media were higher in the FCS group compared to other treatments (P<0.001).
      Leptin-stimulated nuclear oocyte maturation was significantly impaired when
      leptin-induced JAK2/STAT3 and MEK 1/2 activation was suppressed by the inhibitors
      (P<0.001). Steroid secretion of COC was not affected by leptin activation of
      JAK2/STAT3 or MEK 1/2 pathways. In conclusion, JAK2/STAT3 and MEK 1/2 pathways
      mediate the enhancement of nuclear oocyte maturation by leptin; however, neither
      cytoplasmic oocyte maturation nor steroidogenic response of COC were improved in
      the present rabbit model.

PMID- 20032211
TI  - Transient estrogen exposure from birth affects uterine expression of
      developmental markers in neonatal gilts with lasting consequences in pregnant
      adults.
AB  - Disruption of estrogen-sensitive, estrogen receptor (ER)-dependent events during
      porcine uterine development between birth (postnatal day=PND 0) and PND 14
      affects patterns of uterine morphoregulatory gene expression in the neonate with
      lasting consequences for reproductive success. Uterine capacity for conceptus
      support is reduced in pregnant adult gilts exposed to estradiol valerate (EV) for
      14 days from birth. Objectives here were to determine effects of EV exposure from
      birth through PND 13 on neonatal uterine and adult endometrial markers of growth,
      patterning, and remodeling. Targets included the relaxin receptor (RXFP1),
      estrogen receptor-alpha (ESR1) and vascular endothelial growth factor (VEGFA),
      morphoregulatory markers HOXA10 and WNT7A, and the matrix metalloproteinases
      (MMP)2 and MMP9. Gilts were treated daily with EV (50 microg/kg body weight per
      day, i.m.) or corn oil vehicle from birth through PND 13. Uteri were obtained
      from neonates on PND 14 and from adults on pregnancy day 12 (PxD 12). In
      neonates, EV exposure from birth increased uterine RXFP1 gene expression, and
      both ESR1 and VEGFA proteins. At PxD 12, endometrial RXFP1 mRNA remained
      elevated, while ESR1 protein was reduced. Early EV treatment decreased neonatal
      uterine WNT7A, but increased HOXA10 expression. WNT7A expression was reduced in
      EV-treated adults. Transient EV exposure increased MMP9 transcripts at PND 14,
      whereas both latent and active MMP9 activity was increased due to early EV
      treatment in adults on PxD 12. Results support the hypothesis that transient,
      estrogen-induced disruption of porcine uterine development from birth alters
      early programming events that lead to functional consequences in the adult.

PMID- 20032212
TI  - A model of the acrosome reaction progression via the acrosomal membrane-anchored
      protein equatorin.
AB  - It is important to establish a reliable and progressive model of the acrosome
      reaction. Here, we present a progression model of the acrosome reaction centering
      around the acrosomal membrane-anchored protein equatorin (MN9), comparing the
      staining pattern traced by MN9 antibody immunofluorescence with that traced by
      Arachis hypogaea agglutinin (PNA)-FITC. Prior to the acrosome reaction, equatorin
      was present in both the anterior acrosome and the equatorial segment. Since sperm
      on zona pellucida showed various staining patterns, MN9-immunostaining patterns
      were classified into four stages: initial, early, advanced, and final. As the
      acrosome reaction progressed from the initial to the early stage, equatorin
      spread from the peripheral region of the anterior acrosome toward the center of
      the equatorial segment, gradually over the entire region of the equatorial
      segment during the advanced stage, and finally uniformly at the equatorial
      segment at the final stage. In contrast, the PNA-FITC signals spread more quickly
      from the peripheral region of the acrosome toward the entire equatorial segment,
      while decreasing in staining intensity, and finally became weak at the final
      stage. MN9-immunogold electron microscopy showed equatorin on the hybrid vesicles
      surrounded by amorphous substances at advanced stage of acrosome reaction.
      Equatorin decreased in molecular mass from 40-60 to 35 kDa, and the signal
      intensity of 35 kDa equatorin increased as the acrosome reaction progressed.
      Thus, the established equatorin-based progression model will be useful for
      analyzing not only the behavior of equatorin but also of other molecules of
      interest involved in the acrosome reaction.

PMID- 20032213
TI  - Is interleukin-1alpha a luteotrophic or luteolytic agent in cattle?
AB  - Cytokines are thought to regulate prostaglandin (PG) secretion in the bovine
      endometrium. However, there is no consensus about the role of interleukin-1alpha
      (IL1A) on PG secretion. The objective of this study was to examine the influence
      of IL1A on basal and interferon-tau (IFNT)-regulated PG in vitro secretion, as
      well its effects on PG secretion, progesterone (P(4)) output, and corpus luteum
      (CL) in vivo lifespan. Explants of bovine endometrium (days 16-17 of the estrous
      cycle or early pregnancy) were stimulated with IL1A (10 ng/ml), IFNT (30 ng/ml),
      or IL1A combined with IFN. IL1A alone strongly stimulated luteotrophic PGE(2)
      secretion by endometrial tissues of both pregnant and nonpregnant cows. IL1A also
      stimulated luteolytic PGF(2alpha) output in the late luteal phase. IFNT augmented
      the stimulatory effect of IL1A on PGE(2) secretion. In an in vivo experiment,
      saline or IL1A at different doses (0.001-10 microg/per animal) was applied to the
      uterine lumen on day 16 of the cycle. Only the highest dose of IL1A caused a
      temporal increase in PGF(2alpha) secretion, while it had no effect on P(4)
      secretion or CL lifespan. Application of 0.1 and 1 microg IL1A stimulated P(4)
      and PGE(2) output and prolonged the CL lifespan. Although IL1A may stimulate in
      vitro luteolytic PGF(2alpha) secretion during the estrous cycle, it only acts as
      a luteotrophic factor in vivo. IL1A increased luteotrophic PGE(2) and P(4)
      output, inhibiting spontaneous luteolysis. These luteotrophic effects may result
      in appropriate luteal development and function in cows during the estrous cycle
      and early pregnancy.

PMID- 20032214
TI  - Pentoxifylline added to freezing or post-thaw extenders does not improve the
      survival or in vitro fertilising capacity of boar spermatozoa.
AB  - This study evaluated whether pentoxifylline added to freezing and thawing
      extenders influenced the function of boar spermatozoa. In Experiment 1, pooled
      ejaculated sperm-rich fractions were frozen in 0.5 ml straws after dilution in
      extender supplemented with pentoxifylline to a final concentration of 0, 2, 4, 8,
      16 or 32 mM. The addition of 4, 8, 16 and 32 mM pentoxifylline to the freezing
      extender significantly decreased the progressive and total motility of
      spermatozoa. The percentage of viable spermatozoa with intact acrosomes as well
      as the penetration rate and the efficiency of fertilisation were significantly
      lower in pentoxifylline-treated groups compared with the untreated control. In
      Experiment 2, a pool of three straws with 'good' post-thaw sperm quality
      parameters and another three straws with 'poor' sperm quality were diluted in
      extender with 0, 1, 2, 4, 8, 16 or 32 mM pentoxifylline. Post-thaw samples with
      both 'good' and 'poor' sperm quality with 0, 2, 4, 8 and 16 mM were used to
      assess IVF parameters. The addition of pentoxifylline to post-thaw extender did
      not improve the post-thaw motility or viability of spermatozoa compared with the
      control. The in vitro penetration was higher (P<0.05) than the control for
      oocytes fertilised with spermatozoa that were thawed and incubated in extender
      with 4, 8 and 16 mM pentoxifylline. However, no differences were observed in the
      efficiency of fertilisation. We conclude that pentoxifylline, as a supplement
      added to the freezing extender, has a deleterious effect and that it does not
      improve the survival or in vitro fertilising efficiency of frozen-thawed boar
      spermatozoa when added after thawing.

PMID- 20032215
TI  - Luteal blood flow and concentrations of circulating progesterone and other
      hormones associated with a simulated pulse of 13,14-dihydro-15-keto-prostaglandin
      F2alpha in heifers.
AB  - Progesterone and luteal blood flow effects of an i.u. 2-h infusion of 0.25 mg/h
      of prostaglandin F(2)(alpha) (PGF) that simulated a natural pulse of 13,14
      dihydro-15-keto-PGF (PGFM) were compared to the effects of a single bolus i.u.
      injection of PGF (4 mg) that induced complete luteolysis in heifers. Blood
      sampling and an estimate of the percentage of luteal area with colour-Doppler
      signals of blood flow were performed every 2 min for 20 min and less frequently
      thereafter for 6 h. After the beginning of PGF infusion or a bolus injection,
      progesterone increased to a peak at 14 and 10 min respectively, and was
      accompanied by an increase in blood flow in the bolus group but not in the
      infusion group. Progesterone then decreased for 1 or 2 h and was accompanied by a
      continued elevation in blood flow in the PGF bolus group and by a slight increase
      in the PGF infusion group. Progesterone then rebounded in both groups, but the
      rebound was greater in the infusion group. Blood flow decreased during the
      descending arm of the progesterone rebound. Cortisol and prolactin began to
      increase 6 min after the bolus PGF injection but did not increase during or after
      PGF infusion. The increases in cortisol, prolactin and blood flow after a PGF
      bolus treatment but not during a simulated PGFM pulse indicated that the bolus
      treatment was pharmacologic, and its use may lead to faulty conclusions on the
      nature of physiologic luteolysis. The comparisons between progesterone and blood
      flow are novel.

PMID- 20032216
TI  - The borrelial fibronectin-binding protein RevA is an early antigen of human Lyme
      disease.
AB  - Previous studies using small numbers of serum samples from human patients and
      experimentally infected animals identified the frequent presence of antibodies
      recognizing RevA, a borrelial fibronectin-binding outer surface protein. We now
      demonstrate that most examined Lyme disease spirochetes from North America and
      Europe contain genes encoding RevA proteins, some with extensive regions of
      conservation and others with moderate diversity. Line blot analyses using
      recombinant RevA from two diverse Lyme disease spirochetes of RevA and serum
      samples from culture-confirmed human Lyme disease patients from the United States
      (n = 46, mainly with early Lyme disease) and Germany (>500, with early and late
      manifestations of Lyme disease) were performed. The results indicated that a
      sizable proportion of patients produced antibodies that recognized recombinant
      RevA. Overall, RevA-based serological studies were less sensitive and less
      specific than other assay types, such as the VlsE-based C6 peptide assay.
      However, sera from patients in the initial stages of Lyme disease contained
      antibodies against RevA, demonstrating that this protein is expressed early in
      human infection. Thus, RevA may be a useful target for preventative or curative
      therapies.

PMID- 20032217
TI  - Immunologic indicators of clinical progression during canine Leishmania infantum
      infection.
AB  - In both dogs and humans Leishmania infantum infection is more prevalent than
      disease, as infection often does not equate with clinical disease. Previous
      studies additively indicate that advanced clinical visceral leishmaniasis is
      characterized by increased production of anti-Leishmania antibodies, Leishmania
      specific lymphoproliferative unresponsiveness, and decreased production of gamma
      interferon (IFN-gamma) with a concomitant increase of interleukin-10 (IL-10). In
      order to differentiate infection versus progressive disease for better disease
      prognostication, we temporally evaluated humoral and cellular immunologic
      parameters of naturally infected dogs. The work presented here describes for the
      first time the temporal immune response to natural autochthonous L. infantum
      infection in foxhounds within the United States. Several key changes in
      immunological parameters should be considered when differentiating infection
      versus clinical disease, including a dramatic rise in IgG production, progressive
      increases in antigen-specific peripheral blood mononuclear cell proliferation,
      and IFN-gamma production. Polysymptomatic disease is precluded by increased IL-10
      production and consistent detection of parasite kinetoplast DNA in whole blood.
      This clinical presentation and the immuno-dysregulation mirror those observed in
      human patients, indicating that this animal model will be very useful for testing
      immunomodulatory anti-IL-10 and other therapies.

PMID- 20032218
TI  - Oral administration of beta-1,3/1,6-glucan to dogs temporally changes total and
      antigen-specific IgA and IgM.
AB  - The effect of oral administration of beta-1,3/1,6-glucans from Saccharomyces
      cerevisiae on humoral immunity in domestic dogs is not known. In this study, 15
      beagle dogs were orally given MacroGard tablets, which contain 150 mg of this
      beta-glucan, daily for 4 weeks. At the end of this period, the total serum
      immunoglobulin A (IgA) level decreased significantly in the group treated with
      the glucan compared to that in the control group as well as compared to the
      concentrations before supplementation. In contrast, the total serum IgM level
      rose significantly, whereas no effect on the IgG level occurred. Similar changes
      were seen in Bordetella-specific IgA and IgM titers following vaccination during
      the supplementation period. The IgA concentration also became significantly lower
      in the saliva and tears of the glucan group than in the placebo group. The
      effects disappeared 1 week after the cessation of the supplementation. In
      conclusion, the results showed a temporary change in the isotype profile during
      glucan supplementation.

PMID- 20032219
TI  - Real-time PCR with serum samples is indispensable for early diagnosis of acute Q
      fever.
AB  - The world's largest Q fever outbreak is ongoing in The Netherlands with around
      3,000 confirmed cases since the first half of 2007. Increased awareness has
      resulted in early referral of patients for diagnostics. An important drawback to
      serological diagnosis of acute Q fever is the lag phase in antibody response.
      Therefore, we evaluated the performance of a real-time PCR for detection of
      Coxiella burnetii DNA using serum samples from patients with acute Q fever. PCR,
      targeting IS1111, was retrospectively performed on acute-phase and follow-up
      convalescent-phase serum samples from 65 patients with acute Q fever as diagnosed
      by immunofluorescence assay. The results obtained by PCR were related to disease
      stage as defined by subsequent appearance of phase II IgM, phase II IgG, phase I
      IgM, and phase I IgG (IgM-II, IgG-II, IgM-I, and IgG-I, respectively) antibodies
      and time since onset of disease. In addition, we analyzed seronegative acute
      phase serum samples from patients with inconclusive Q fever serology, because no
      convalescent-phase serum samples were available. PCR was scored positive in 49/50
      (98%) seronegative sera, 9/10 (90%) sera with isolated IgM-II antibodies, 3/13
      (23%) sera with IgM-II/IgG-II antibodies, 2/41 (5%) sera with IgM-II/IgG-II/IgM-I
      antibodies, 0/15 (0%) sera with IgM-II/IgG-II/IgM-I/IgG-I antibodies, and 0/1
      (0%) serum sample with IgM-II/IgG-II/IgG-I antibodies. The latest time point
      after onset of disease in which C. burnetii DNA could be detected was at day 17.
      In patients with inconclusive Q fever serology, PCR was positive in 5/50 (10%)
      cases. We conclude that real-time PCR with serum samples is indispensable for
      early diagnosis of acute Q fever. C. burnetii DNA becomes undetectable in serum
      as the serological response develops.

PMID- 20032221
TI  - Rituximab: a potential therapeutic advance in scleroderma: what is the evidence?

PMID- 20032220
TI  - Long-term treatment of relapsing Wegener's granulomatosis with 15
      deoxyspergualin.
AB  - OBJECTIVE: To determine the safety and efficacy of prolonged treatment with 15
      deoxyspergualin (DSG, gusperimus) in patients with relapsing WG. METHODS:
      Patients with relapsing WG treated with DSG were studied. Other
      immunosuppressants except corticosteroids were withdrawn and DSG, 0.5 mg/kg/day,
      self-administered subcutaneously for up to 21 days, in 28-day cycles. The cycle
      was terminated early for white blood cell count <4 x 10(9)/l. The prednisolone
      dose was adjusted according to the clinical state. End points were disease
      remission, relapse, Birmingham Vasculitis Activity Score (BVAS), prednisolone
      dose and safety. RESULTS: Eleven patients, five (45%) of whom were female,
      received a total of 15 treatment periods with DSG. The median (range) duration of
      each treatment period was 6.8 (3.3-15.9) months. Ten (90.9%) patients responded
      in 13/15 courses after a median of 1.7 (0.7-2.7) months and six (54.5%) achieved
      remission after 7.7 (1.9-13.5) months. Two (18.2%) patients relapsed while
      continuing to receive DSG. Remission was maintained in other patients while DSG
      was continued. However, 7/8 relapsed after DSG withdrawal. The median BVAS fell
      from 10 (3-22) at baseline to 3 (0-16) at the end of each treatment period (P =
      0.002). Median prednisolone doses were reduced from 20 (5-30) mg/day at baseline
      to 10 (5-25) mg/day at the end of each treatment period (P = 0.052). Three severe
      adverse events occurred in two patients. CONCLUSIONS: Extended treatment with DSG
      was effective in the majority of patients with relapsing WG and permitted
      prednisolone reduction. There was no unexpected toxicity associated with
      prolonged DSG administration.

PMID- 20032222
TI  - Correlations among mineral components, progressive calcification process and
      clinical symptoms of calcific tendonitis.
AB  - OBJECTIVE: To establish the correlations among the mineral components,
      progressive calcification process and clinical symptoms of calcific tendonitis.
      METHODS: The morphology of the calcified deposits on the shoulders of 28 patients
      with calcific tendonitis was determined by high-resolution ultrasonography. The
      calcified deposit from each patient was aspirated and determined by the Fourier
      transform infrared and Raman microspectroscopies. The curve-fitting program was
      applied to estimate the chemical component in the calcified deposits of calcific
      tendonitis. RESULTS: The morphology of calcified deposits for 28 patients was
      classified into four shapes: arc shape (7 patients), fragmented/punctuate shape
      (4 patients), nodular shape (13 patients) and cystic shape (4 patients). These
      classified shapes markedly correlated with the pain levels in patients. The
      infrared spectra of all the calcified deposits for 28 patients were easily
      classified into three types in the blind study and corresponded to the formative,
      resting and resorptive phases in the progressive calcification process of
      calcific tendonitis. With the progressive calcification, the IR wavenumber at
      1018 cm(-1) assigned to poorly crystalline, non-stoichiometric apatite for the
      formative phase was shifted to 1028 cm(-1) for the resting phase and then to 1031
      cm(-1) due to matured crystalline stoichiometric apatite for the resorptive
      phase. The curve-fitted results revealed that calcified deposits in calcific
      tendonitis were composed of different quantities of A-type and B-type carbonated
      apatites in the three phases. A significant difference was found in carbonated
      apatite content among the three phases (P < 0.001). CONCLUSIONS: The different
      quantities of A-type and B-type carbonated apatites determined by vibrational
      microspectroscopy in calcified deposits were well correlated with those of the
      four shapes of morphologic classification, with the three phases in the
      progressive calcification process and with the clinical symptoms of calcific
      tendonitis.

PMID- 20032223
TI  - Predictors of response to anti-TNF therapy in ankylosing spondylitis: results
      from the British Society for Rheumatology Biologics Register.
AB  - OBJECTIVE: Few data exist on the use of anti-TNF drugs for AS during routine
      clinical use in the UK. This report describes an improvement in Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis
      Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a
      national prospective observational register. METHODS: The British Society for
      Rheumatology Biologics Register (BSRBR) recruited patients starting anti-TNF
      therapy for AS between 2002 and 2006. Multivariable linear regression models were
      used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6
      months. Covariates included age, gender, disease duration, baseline BASDAI and
      BASFI, presence of raised inflammatory markers (defined as twice the upper limit
      of normal) and DMARD therapy. RESULTS: The cohort was young (median age 43 years)
      and 82% were males. Median baseline BASDAI was 7.6 and BASFI 7.9. At 6 months,
      the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U, respectively; 52%
      reached a BASDAI50. Patients with raised inflammatory markers at the start of
      therapy had a 0.9-U (95% CI 0.2, 1.5) better improvement in BASDAI compared with
      those without. Lesser responses were seen in those with higher baseline BASFI
      scores. Women had a 1.1-U (95% CI 0.3, 2.0) greater improvement in BASFI at 6
      months, as did those who were receiving concurrent DMARD therapy [0.9 U (95% CI
      0.2, 1.7)]. CONCLUSIONS: The majority of patients receiving anti-TNF therapy for
      AS during routine care demonstrated an improvement in disease activity. Raised
      inflammatory markers at the start of therapy predicted a greater improvement in
      BASDAI, identifying a group of patients who may be more responsive to anti-TNF
      therapies, although the results were not confined to this group.

PMID- 20032225
TI  - NICE guidance on rheumatoid arthritis: implications and challenges for
      rheumatologists.

PMID- 20032224
TI  - Green tea extract inhibits chemokine production, but up-regulates chemokine
      receptor expression, in rheumatoid arthritis synovial fibroblasts and rat
      adjuvant-induced arthritis.
AB  - OBJECTIVE: Evaluation of the efficacy of green tea extract (GTE) in regulating
      chemokine production and chemokine receptor expression in human RA synovial
      fibroblasts and rat adjuvant-induced arthritis (AIA). METHODS: Fibroblasts
      isolated from human RA synovium were used in the study. Regulated upon activation
      normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant
      protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)alpha/CXCL1 and IL-8/CXCL8
      production was measured by ELISA. Western blotting was used to study the
      phosphorylation of protein kinase C (PKC)delta and c-Jun N-terminal kinases
      (JNK). Chemokine and chemokine receptor expression was determined by quantitative
      RT-PCR. The benefit of GTE administration in rat AIA was determined. RESULTS: GTE
      (2.5-40 microg/ml) inhibited IL-1beta-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5,
      GROalpha/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P <
      0.05). However, GTE inhibited MCP-1/CCL2 and GROalpha/CXCL1 mRNA synthesis in RA
      synovial fibroblasts. Furthermore, GTE also inhibited IL-1beta-induced
      phosphorylation of PKCdelta, the signalling pathway mediating IL-1beta-induced
      chemokine production. Interestingly, GTE preincubation enhanced constitutive and
      IL-1beta-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE
      administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was
      accompanied by a decrease in MCP-1/CCL2 and GROalpha/CXCL1 levels and enhanced
      CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered
      rats. CONCLUSIONS: Chemokine receptor overexpression with reduced chemokine
      production by GTE may be one potential mechanism to limit the overall
      inflammation and joint destruction in RA.

PMID- 20032226
TI  - Severe aplastic anaemia following leflunomide therapy.

PMID- 20032227
TI  - Refractory anti-synthetase syndrome treated with rituximab.

PMID- 20032228
TI  - Gadolinium-associated nephrogenic systemic fibrosis in patients with renal
      failure: the need for an interdisciplinary helping network.

PMID- 20032229
TI  - Prediction of functional impairment and remission in rheumatoid arthritis
      patients by biochemical variables and genetic polymorphisms.
AB  - OBJECTIVE: To develop a model to predict RA outcome based on biochemical
      variables and single nucleotide polymorphisms (SNPs). METHODS: We collected
      baseline data from RA patients. SNP genotyping was performed using an
      oligonucleotide microarray. Remission and severe disability were investigated as
      outcomes of the study. Logistic regression models and receiver operating
      characteristic (ROC) curves were used to determine sensitivity (S), specificity
      (Sp) and likelihood ratio (LR). RESULTS: Six hundred and thirty-two patients (375
      in the study and 257 in the validation) were included. Twenty-two out of 152, and
      19 out of 208 patients had an HAQ > 2. The model obtained to predict disability
      included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies,
      ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of
      the IL-4 33T allele had a decreased risk of severe disability. The discriminative
      power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S
      41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in
      remission in the study and validation cohorts, respectively. The model included
      absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene.
      Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased
      probability of remission. The discriminative power had an AUC of 0.842 (95% CI
      0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed
      on the validation cohort. CONCLUSIONS: We have developed two models based on
      laboratory variables that are associated with relevant outcomes for RA patients
      at disease onset.

PMID- 20032230
TI  - Temporal dynamics of 2D motion integration for ocular following in macaque
      monkeys.
AB  - Several recent studies have shown that extracting pattern motion direction is a
      dynamical process where edge motion is first extracted and pattern-related
      information is encoded with a small time lag by MT neurons. A similar dynamics
      was found for human reflexive or voluntary tracking. Here, we bring an essential,
      but still missing, piece of information by documenting macaque ocular following
      responses to gratings, unikinetic plaids, and barber-poles. We found that ocular
      tracking was always initiated first in the grating motion direction with ultra
      short latencies (approximately 55 ms). A second component was driven only 10-15
      ms later, rotating tracking toward pattern motion direction. At the end the open
      loop period, tracking direction was aligned with pattern motion direction
      (plaids) or the average of the line-ending motion directions (barber-poles). We
      characterized the dependency on contrast of each component. Both timing and
      direction of ocular following were quantitatively very consistent with the
      dynamics of neuronal responses reported by others. Overall, we found a remarkable
      consistency between neuronal dynamics and monkey behavior, advocating for a
      direct link between the neuronal solution of the aperture problem and primate
      perception and action.

PMID- 20032231
TI  - Lesions of the auditory cortex impair azimuthal sound localization and its
      recalibration in ferrets.
AB  - The role of auditory cortex in sound localization and its recalibration by
      experience was explored by measuring the accuracy with which ferrets turned
      toward and approached the source of broadband sounds in the horizontal plane. In
      one group, large bilateral lesions were made of the middle ectosylvian gyrus,
      where the primary auditory cortical fields are located, and part of the anterior
      and/or posterior ectosylvian gyrus, which contain higher-level fields. In the
      second group, the lesions were intended to be confined to primary auditory cortex
      (A1). The ability of the animals to localize noise bursts of different duration
      and level was measured before and after the lesions were made. A1 lesions
      produced a modest disruption of approach-to-target responses to short-duration
      stimuli (<500 ms) on both sides of space, whereas head orienting accuracy was
      unaffected. More extensive lesions produced much greater auditory localization
      deficits, again primarily for shorter sounds. In these ferrets, the accuracy of
      both the approach-to-target behavior and the orienting responses was impaired,
      and they could do little more than correctly lateralize the stimuli. Although
      both groups of ferrets were still able to localize long-duration sounds
      accurately, they were, in contrast to ferrets with an intact auditory cortex,
      unable to relearn to localize these stimuli after altering the spatial cues
      available by reversibly plugging one ear. These results indicate that both
      primary and nonprimary cortical areas are necessary for normal sound
      localization, although only higher auditory areas seem to contribute to accurate
      head orienting behavior. They also show that the auditory cortex, and A1 in
      particular, plays an essential role in training-induced plasticity in adult
      ferrets, and that this is the case for both head orienting responses and approach
      to-target behavior.

PMID- 20032232
TI  - Inhibitory odorant signaling in Mammalian olfactory receptor neurons.
AB  - Odorants inhibit as well as excite olfactory receptor neurons (ORNs) in many
      species of animals. Cyclic nucleotide-dependent activation of canonical mammalian
      ORNs is well established but it is still unclear how odorants inhibit these
      cells. Here we further implicate phosphoinositide-3-kinase (PI3K), an
      indispensable element of PI signaling in many cellular processes, in olfactory
      transduction in rodent ORNs. We show that odorants rapidly and transiently
      activate PI3K in the olfactory cilia and in the olfactory epithelium in vitro. We
      implicate known G-protein-coupled isoforms of PI3K and show that they modulate
      not only the magnitude but also the onset kinetics of the electrophysiological
      response of ORNs to complex odorants. Finally, we show that the ability of a
      single odorant to inhibit another can be PI3K dependent. Our collective results
      provide compelling support for the idea that PI3K-dependent signaling mediates
      inhibitory odorant input to mammalian ORNs and at least in part contributes to
      the mixture suppression typically seen in the response of ORNs to complex natural
      odorants.

PMID- 20032234
TI  - Recovery of motoneuron output is delayed in old men following high-intensity
      fatigue.
AB  - Despite an age-related slowing in the contractile properties of the triceps
      surae, inherently low maximal motor unit firing rates (MUFRs) in the soleus are
      unchanged. Fatigue following high-intensity contractions is characterized by
      contractile slowing in conjunction with a reduction in MUFRs in young adults.
      Here we exploit the ageing model of the soleus to assess changes in neuromuscular
      function during fatigue and short-term recovery. We hypothesize that a high
      intensity sustained contraction will cause minimal reductions in MUFRs in young
      and old subjects but that recovery of MUFRs will be delayed in aged subjects. We
      compared the effects of a high-intensity sustained task on the MUFRs of the
      soleus and triceps surae contractile properties in six young (approximately 24
      yr) and six old (approximately 75 yr) men. Various measures of the contractile
      function of the triceps surae were tested during two to six sessions via maximal
      voluntary isometric contractions (MVCs) and tibial nerve stimulation. Populations
      of MUFR trains were recorded from the soleus during brief (approximately 7 s)
      MVCs, a high-intensity (75% MVC) sustained fatiguing task, and brief MVCs
      following task failure at 1, 2, 5, and 10 min. Old men had greater time to task
      failure than the young (approximately 138 and approximately 100 s, respectively).
      Voluntary activation was near maximal (>99%) for all subjects but at task
      failure, decreased to approximately 89% in both groups. Maximal MUFRs, for both
      groups, were reduced by approximately 44% and twitch contraction duration slowed
      by approximately 30% following task failure. Contraction duration recovered
      equally for both groups within 2 min, but maximal MUFRs did not recover until 5
      min in the old compared with 1 min for the young. The surprising fatigue-induced
      reduction in MUFRs was similar for both groups, but despite a similar recovery of
      contractile properties for both, recovery of MUFRs was impaired in the old
      subjects.

PMID- 20032233
TI  - Responses of amygdala neurons to positive reward-predicting stimuli depend on
      background reward (contingency) rather than stimulus-reward pairing (contiguity).
AB  - Prediction about outcomes constitutes a basic mechanism underlying informed
      economic decision making. A stimulus constitutes a reward predictor when it
      provides more information about the reward than the environmental background.
      Reward prediction can be manipulated in two ways, by varying the reward paired
      with the stimulus, as done traditionally in neurophysiological studies, and by
      varying the background reward while holding stimulus-reward pairing constant.
      Neuronal mechanisms involved in reward prediction should also be sensitive to
      changes in background reward independently of stimulus-reward pairing. We tested
      this assumption on a major brain structure involved in reward processing, the
      central and basolateral amygdala. In a 2 x 2 design, we examined the influence of
      rewarded and unrewarded backgrounds on neuronal responses to rewarded and
      unrewarded visual stimuli. Indeed, responses to the unchanged rewarded stimulus
      depended crucially on background reward in a population of amygdala neurons.
      Elevating background reward to the level of the rewarded stimulus extinguished
      these responses, and lowering background reward again reinstated the responses
      without changes in stimulus-reward pairing. None of these neurons responded
      specifically to an inhibitory stimulus predicting less reward compared with
      background (negative contingency). A smaller group of amygdala neurons maintained
      stimulus responses irrespective of background reward, possibly reflecting
      stimulus-reward pairing or visual sensory processes without reward prediction.
      Thus in being sensitive to background reward, the responses of a population of
      amygdala neurons to phasic stimuli appeared to follow the full criteria for
      excitatory reward prediction (positive contingency) rather than reflecting simple
      stimulus-reward pairing (contiguity).

PMID- 20032235
TI  - Temperature modulation of slow and fast cortical rhythms.
AB  - In the local cortical network, spontaneous emergent activity self-organizes in
      rhythmic patterns. These rhythms include a slow one (<1 Hz), consisting in
      alternation of up and down states, and also faster rhythms (10-80 Hz) generated
      during up states. Varying the temperature in the bath between 26 and 41 degrees C
      resulted in a strong modulation of the emergent network activity. Up states
      became shorter for warmer temperatures and longer with cooling, whereas down
      states were shortest at physiological (36-37 degrees C) temperature. The firing
      rate during up states was robustly modulated by temperature, increasing with
      higher temperatures. The sparse firing rate during down states hardly varied with
      temperature, thus resulting in a progressive merging of up and down states for
      temperatures around 30 degrees C. Below 30 degrees C and down to 26 degrees C the
      firing lost rhythmicity, becoming progressively continuous. The slope of the down
      to-up transitions, which reflects the speed of recruitment of the local network,
      was progressively steeper for higher temperatures, whereas wave-propagation speed
      exhibited only a moderate increase. Fast rhythms were particularly sensitive to
      temperature. Broadband high-frequency fluctuations in the local field potential
      were maximal for recordings at 36-38 degrees C. Overall, we found that
      maintaining cortical slices at physiological temperature is critical for the
      generated activity to be analogous to that in vivo. We also demonstrate that
      changes in activity with temperature were not secondary to oxygenation changes.
      Temperature variation sets the in vitro cortical network at different functional
      regimes, allowing the exploration of network activity generation and control
      mechanisms.

PMID- 20032236
TI  - Regulation of the putative TRPV1t salt taste receptor by phosphatidylinositol 4,5
      bisphosphate.
AB  - Regulation of the putative amiloride and benzamil (Bz)-insensitive TRPV1t salt
      taste receptor by phosphatidylinositol 4,5-bisphosphate (PIP(2)) was studied by
      monitoring chorda tympani (CT) taste nerve responses to 0.1 M NaCl solutions
      containing Bz (5 x 10(-6) M; a specific ENaC blocker) and resiniferatoxin (RTX; 0
      10 x 10(-6) M; a specific TRPV1 agonist) in Sprague-Dawley rats and in wildtype
      (WT) and TRPV1 knockout (KO) mice. In rats and WT mice, RTX elicited a biphasic
      effect on the NaCl + Bz CT response, increasing the CT response between 0.25 x
      10(-6) and 1 x 10(-6) M. At concentrations >1 x 10(-6) M, RTX inhibited the CT
      response. An increase in PIP(2) by topical lingual application of U73122 (a
      phospholipase C blocker) or diC8-PIP(2) (a short chain synthetic PIP(2))
      inhibited the control NaCl + Bz CT response and decreased its sensitivity to RTX.
      A decrease in PIP(2) by topical lingual application of phenylarsine oxide (a
      phosphoinositide 4 kinase blocker) enhanced the control NaCl + Bz CT response,
      increased its sensitivity to RTX stimulation, and inhibited the desensitization
      of the CT response at RTX concentrations >1 x 10(-6) M. The ENaC-dependent NaCl
      CT responses were not altered by changes in PIP(2). An increase in PIP(2)
      enhanced CT responses to sweet (0.3 M sucrose) and bitter (0.01 M quinine)
      stimuli. RTX produced the same increase in the Bz-insensitive Na(+) response when
      present in salt solutions containing 0.1 M NaCl + Bz, 0.1 M monosodium glutamate
      + Bz, 0.1 M NaCl + Bz + 0.005 M SC45647, or 0.1 M NaCl + Bz + 0.01 M quinine. No
      effect of RTX was observed on CT responses in WT mice and rats in the presence of
      the TRPV1 blocker N-(3-methoxyphenyl)-4-chlorocinnamide (1 x 10(-6) M) or in
      TRPV1 KO mice. We conclude that PIP(2) is a common intracellular effector for
      sweet, bitter, umami, and TRPV1t-dependent salt taste, although in the last case,
      PIP(2) seems to directly regulate the taste receptor protein itself, i.e., the
      TRPV1 ion channel or its taste receptor variant, TRPV1t.

PMID- 20032237
TI  - Frequency-specific modulation of vestibular-evoked sway responses in humans.
AB  - Galvanic vestibular stimulation (GVS) results in characteristic muscle and whole
      body responses in humans maintaining standing balance. However, the relationship
      between these two vestibular-evoked responses remains elusive. This study seeks
      to determine whether mechanical filtering from conversion of lower-limb muscle
      activity to body sway, during standing balance, can be used to attenuate sway
      while maintaining biphasic lower-limb muscle responses using frequency-limited
      stochastic vestibular stimulation (SVS). We hypothesized that SVS deprived of
      frequencies <2 Hz would evoke biphasic muscle responses with minimal whole-body
      sway due to mechanical filtering of the higher-frequency muscle responses.
      Subjects were exposed to five stimulus bandwidths: two meant to induce sway
      responses (0-1 and 0-2 Hz) and three to dissociate vestibular-evoked muscle
      responses from whole-body sway (0-25, 1-25, and 2-25 Hz). Two main results
      emerged: 1) SVS-related sway was attenuated when frequencies <2 Hz were excluded,
      whereas multiphasic muscle and force responses were retained; and 2) the gain of
      the estimated transfer functions exhibited successive low-pass filtering of
      vestibular stimuli during conversion to muscle activity, anteroposterior (AP)
      moment, and sway. This successive low-pass filtering limited the transfer of
      signal power to frequencies <20 Hz in muscle activity, <5 Hz in AP moment, and <2
      Hz in AP trunk sway. Consequently, the present results show that SVS delivered at
      frequencies >2 Hz to standing humans do not cause a destabilizing whole-body sway
      response but are associated with the typical biphasic lower-limb muscle
      responses.

PMID- 20032238
TI  - Neural representation of subjective value under risk and ambiguity.
AB  - Risk and ambiguity are two conditions in which the consequences of possible
      outcomes are not certain. Under risk, the probabilities of different outcomes can
      be estimated, whereas under ambiguity, even these probabilities are not known.
      Although most people exhibit at least some aversion to both risk and ambiguity,
      the degree of these aversions is largely uncorrelated across subjects, suggesting
      that risk aversion and ambiguity aversion are distinct phenomena. Previous
      studies have shown differences in brain activations for risky and ambiguous
      choices and have identified neural mechanisms that may mediate transitions from
      conditions of ambiguity to conditions of risk. Unknown, however, is whether the
      value of risky and ambiguous options is necessarily represented by two distinct
      systems or whether a common mechanism can be identified. To answer this question,
      we compared the neural representation of subjective value under risk and
      ambiguity. fMRI was used to track brain activation while subjects made choices
      regarding options that varied systematically in the amount of money offered and
      in either the probability of obtaining that amount or the level of ambiguity
      around that probability. A common system, consisting of at least the striatum and
      the medial prefrontal cortex, was found to represent subjective value under both
      conditions.

PMID- 20032239
TI  - Afferent contribution to locomotor muscle activity during unconstrained
      overground human walking: an analysis of triceps surae muscle fascicles.
AB  - Plantar flexor series elasticity can be used to dissociate muscle-fascicle and
      muscle-tendon behavior and thus afferent feedback during human walking. We used
      electromyography (EMG) and high-speed ultrasonography concomitantly to monitor
      muscle activity and muscle fascicle behavior in 19 healthy volunteers as they
      walked across a platform. On random trials, the platform was dropped (8 cm, 0.9 g
      acceleration) or held at a small inclination (up to +/-3 degrees in the
      parasagittal plane) with respect to level ground. Dropping the platform in the
      mid and late phases of stance produced a depression in the soleus muscle activity
      with an onset latency of about 50 ms. The reduction in ground reaction force also
      unloaded the plantar flexor muscles. The soleus muscle fascicles shortened with a
      minimum delay of 14 ms. Small variations in platform inclination produced
      significant changes in triceps surae muscle activity; EMG increased when stepping
      on an inclined surface and decreased when stepping on a declined surface. This
      sensory modulation of the locomotor output was concomitant with changes in
      triceps surae muscle fascicle and gastrocnemius tendon length. Assuming that
      afferent activity correlates to these mechanical changes, our results indicate
      that within-step sensory feedback from the plantar flexor muscles automatically
      adjusts muscle activity to compensate for small ground irregularities. The
      delayed onset of muscle fascicle movement after dropping the platform indicates
      that at least the initial part of the soleus depression is more likely mediated
      by a decrease in force feedback than length-sensitive feedback, indicating that
      force feedback contributes to the locomotor activity in human walking.

PMID- 20032240
TI  - Antisaccade cost is modulated by contextual experience of location probability.
AB  - It is well known that pro- and antisaccades may deploy different cognitive
      processes. However, the specific reason why antisaccades have longer latencies
      than prosaccades is still under debate. In three experiments, we studied the
      factors contributing to the antisaccade cost by taking attentional orienting and
      target location probabilities into account. In experiment 1, using a new
      antisaccade paradigm, we directly tested Olk and Kingstone's hypothesis, which
      attributes longer antisaccade latency to the time it takes to reorient from the
      visual target to the opposite saccadic target. By eliminating the reorienting
      component in our paradigm, we found no significant difference between the
      latencies of the two saccade types. In experiment 2, we varied the proportion of
      prosaccades made to certain locations and found that latencies in the high
      location-probability (75%) condition were faster than those in the low location
      probability condition. Moreover, antisaccade latencies were significantly longer
      when location probability was high. This pattern can be explained by the notion
      of competing pathways for pro- and antisaccades in findings of others. In
      experiment 3, we further explored the degrees of modulation of location
      probability by decreasing the magnitude of high probability from 75 to 65%. We
      again observed a pattern similar to that seen in experiment 2 but with smaller
      modulation effects. Together, these experiments indicate that the reorienting
      process is a critical factor in producing the antisaccade cost. Furthermore, the
      antisaccade cost can be modulated by probabilistic contextual information such as
      location probabilities.

PMID- 20032241
TI  - Rectification of the EMG signal impairs the identification of oscillatory input
      to the muscle.
AB  - Rectification of EMG signals is a common processing step used when performing
      electroencephalographic-electromyographic (EEG-EMG) coherence and EMG-EMG
      coherence. It is well known, however, that EMG rectification alters the power
      spectrum of the recorded EMG signal (interference EMG). The purpose of this study
      was to determine whether rectification of the EMG signal influences the
      capability of capturing the oscillatory input to a single EMG signal and the
      common oscillations between two EMG signals. Several EMG signals were
      reconstructed from experimentally recorded EMG signals from the surface of the
      first dorsal interosseus muscle and were manipulated to have an oscillatory input
      or common input (for pairs of reconstructed EMG signals) at various frequency
      bands (in Hz: 0-12, 12-30, 30-50, 50-100, 100-150, 150-200, 200-250, 250-300, and
      300-400), one at a time. The absolute integral and normalized integral of power,
      peak power, and peak coherence (for pairs of EMG signals) were quantified from
      each frequency band. The power spectrum of the interference EMG accurately
      detected the changes to the oscillatory input to the reconstructed EMG signal,
      whereas the power spectrum of the rectified EMG did not. Similarly, the EMG-EMG
      coherence between two interference EMG signals accurately detected the common
      input to the pairs of reconstructed EMG signals, whereas the EMG-EMG coherence
      between two rectified EMG signals did not. The frequency band from 12 to 30 Hz in
      the power spectrum of the rectified EMG and the EMG-EMG coherence between two
      rectified signals was influenced by the input from 100 to 150 Hz but not from the
      input from 12 to 30 Hz. The study concludes that the power spectrum of the EMG
      and EMG-EMG coherence should be performed on interference EMG signals and not on
      rectified EMG signals because rectification impairs the identification of the
      oscillatory input to a single EMG signal and the common oscillatory input between
      two EMG signals.

PMID- 20032242
TI  - fMRI-adaptation studies of viewpoint tuning in the extrastriate and fusiform body
      areas.
AB  - People are easily able to perceive the human body across different viewpoints,
      but the neural mechanisms underpinning this ability are currently unclear. In
      three experiments, we used functional MRI (fMRI) adaptation to study the view
      invariance of representations in two cortical regions that have previously been
      shown to be sensitive to visual depictions of the human body--the extrastriate
      and fusiform body areas (EBA and FBA). The BOLD response to sequentially
      presented pairs of bodies was treated as an index of view invariance.
      Specifically, we compared trials in which the bodies in each image held identical
      poses (seen from different views) to trials containing different poses. EBA and
      FBA adapted to identical views of the same pose, and both showed a progressive
      rebound from adaptation as a function of the angular difference between views, up
      to approximately 30 degrees. However, these adaptation effects were eliminated
      when the body stimuli were followed by a pattern mask. Delaying the mask onset
      increased the response (but not the adaptation effect) in EBA, leaving FBA
      unaffected. We interpret these masking effects as evidence that view-dependent
      fMRI adaptation is driven by later waves of neuronal responses in the regions of
      interest. Finally, in a whole brain analysis, we identified an anterior region of
      the left inferior temporal sulcus (l-aITS) that responded linearly to stimulus
      rotation, but showed no selectivity for bodies. Our results show that body
      selective cortical areas exhibit a similar degree of view-invariance as other
      object selective areas--such as the lateral occipitotemporal area (LO) and
      posterior fusiform gyrus (pFs).

PMID- 20032243
TI  - Effect of conditioned stimulus parameters on timing of conditioned Purkinje cell
      responses.
AB  - Pavlovian eyeblink conditioning is a useful experimental model for studying
      adaptive timing, an important aspect of skilled movements. The conditioned
      response (CR) is precisely timed to occur just before the onset of the expected
      unconditioned stimulus (US). The timing can be changed immediately, however, by
      varying parameters of the conditioned stimulus (CS). It has previously been shown
      that increasing the intensity of a peripheral CS or the frequency of a CS
      consisting of a train of stimuli to the mossy fibers shortens the latency of the
      CR. The adaptive timing of behavioral CRs probably reflects the timing of an
      underlying learned inhibitory response in cerebellar Purkinje cells. It is not
      known how the latency of this Purkinje cell CR is controlled. We have recorded
      form Purkinje cells in conditioned decerebrate ferrets while increasing the
      intensity of a peripheral CS or the frequency of a mossy fiber CS. We observe
      changes in the timing of the Purkinje cell CR that match the behavioral effects.
      The results are consistent with the effect of CS parameters on behavioral CR
      latency being caused by corresponding changes in Purkinje cell CRs. They suggest
      that synaptic temporal summation may be one of several mechanisms underlying
      adaptive timing of movements.

PMID- 20032244
TI  - Generation of spatiotemporally correlated spike trains and local field potentials
      using a multivariate autoregressive process.
AB  - Experimental advances allowing for the simultaneous recording of activity at
      multiple sites have significantly increased our understanding of the
      spatiotemporal patterns in neural activity. The impact of such patterns on neural
      coding is a fundamental question in neuroscience. The simulation of spike trains
      with predetermined activity patterns is therefore an important ingredient in the
      study of potential neural codes. Such artificially generated spike trains could
      also be used to manipulate cortical neurons in vitro and in vivo. Here, we
      propose a method to generate spike trains with given mean firing rates and cross
      correlations. To capture this statistical structure we generate a point process
      by thresholding a stochastic process that is continuous in space and discrete in
      time. This stochastic process is obtained by filtering Gaussian noise through a
      multivariate autoregressive (AR) model. The parameters of the AR model are
      obtained by a nonlinear transformation of the point-process correlations to the
      continuous-process correlations. The proposed method is very efficient and allows
      for the simulation of large neural populations. It can be optimized to the
      structure of spatiotemporal correlations and generalized to nonstationary
      processes and spatiotemporal patterns of local field potentials and spike trains.

PMID- 20032246
TI  - Tuning perceptual competition.
AB  - The ability to notice relevant visual information has been assumed to be
      determined both by the relative salience of relevant information compared with
      distracters within a given display and by voluntary allocation of attention
      toward intended goals. A dominance of either of these two mechanisms in stimulus
      processing has been claimed by different theories. A central question in this
      context is to what degree and how task irrelevant signals can influence
      processing of target information. In the present study, participants had to
      detect a luminance change in various conditions among others against an
      irrelevant orientation change. The saliency of the latter was systematically
      varied and was found to be predictive for the proportion of detected information
      when relevant and irrelevant information were spatially separated but not when
      they overlapped. Weighting and competition of incoming signals was reflected in
      the amplitude of the N1pc component of the event-related potential. Initial
      orientation of attention toward the irrelevant element had to be followed by a
      reallocation process, reflected in an N2pc. The control of conflicting
      information additionally evoked a fronto-central N2 that varied with the amount
      of competition induced. Thus the data support models that assume that attention
      is a dynamic interplay of bottom-up and top-down processes that may be mediated
      via a common dynamic neural network.

PMID- 20032245
TI  - Representations of conspecific song by starling secondary forebrain auditory
      neurons: toward a hierarchical framework.
AB  - The functional organization giving rise to stimulus selectivity in higher-order
      auditory neurons remains under active study. We explored the selectivity for
      motifs, spectrotemporally distinct perceptual units in starling song, recording
      the responses of 96 caudomedial mesopallium (CMM) neurons in European starlings
      (Sturnus vulgaris) under awake-restrained and urethane-anesthetized conditions. A
      subset of neurons was highly selective between motifs. Selectivity was correlated
      with low spontaneous firing rates and high spike timing precision, and all but
      one of the selective neurons had similar spike waveforms. Neurons were further
      tested with stimuli in which the notes comprising the motifs were manipulated.
      Responses to most of the isolated notes were similar in amplitude, duration, and
      temporal pattern to the responses elicited by those notes in the context of the
      motif. For these neurons, we could accurately predict the responses to motifs
      from the sum of the responses to notes. Some notes were suppressed by the motif
      context, such that removing other notes from motifs unmasked additional
      excitation. Models of linear summation of note responses consistently
      outperformed spectrotemporal receptive field models in predicting responses to
      song stimuli. Tests with randomized sequences of notes confirmed the predictive
      power of these models. Whole notes gave better predictions than did note
      fragments. Thus in CMM, auditory objects (motifs) can be represented by a linear
      combination of excitation and suppression elicited by the note components of the
      object. We hypothesize that the receptive fields arise from selective convergence
      by inputs responding to specific spectrotemporal features of starling notes.

PMID- 20032247
TI  - The functional anatomy of a perceptual decision in the human brain.
AB  - Our ability to make rapid decisions based on sensory information belies the
      complexity of the underlying computations. Recently, "accumulator" models of
      decision making have been shown to explain the activity of parietal neurons as
      macaques make judgments concerning visual motion. Unraveling the operation of a
      decision-making circuit, however, involves understanding both the responses of
      individual components in the neural circuitry and the relationships between them.
      In this functional magnetic resonance imaging study of the decision process in
      humans, we demonstrate that an accumulator model predicts responses to visual
      motion in the intraparietal sulcus (IPS). Significantly, the metrics used to
      define responses within the IPS also reveal distinct but interacting nodes in a
      circuit, including early sensory detectors in visual cortex, the visuomotor
      integration system of the IPS, and centers of cognitive control in the prefrontal
      cortex, all of which collectively define a perceptual decision-making network.

PMID- 20032248
TI  - Polymorphisms associated with resistance and cross-resistance to aminoglycosides
      and capreomycin in Mycobacterium tuberculosis isolates from South Korean Patients
      with drug-resistant tuberculosis.
AB  - The aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic
      polypeptide capreomycin are all widely used in second-line therapy for patients
      who develop multidrug-resistant tuberculosis. We have characterized a set of 106
      clinical isolates of Mycobacterium tuberculosis using phenotypic drug
      susceptibility testing (DST) to determine the extent of resistance to each agent
      and cross-resistance between agents. These results were compared with
      polymorphisms in the DNA sequences of ribosome-associated genes previously
      implicated in resistance and with the clinical outcomes of subjects from whom
      these isolates were obtained. Thirty-six (34%) of these isolates displayed
      resistance to one or more of these agents, and the majority of these (20 of 36)
      showed cross-resistance to one or more agents. Most (33 of 36) of the resistant
      isolates showed polymorphisms in the 16S ribosome components RpsL and rrs. Three
      resistant strains (3 of 36) were identified that had no known polymorphisms in
      ribosomal constituents. For kanamycin and streptomycin, molecular DST
      significantly outperformed phenotypic DST using the absolute concentration method
      for predicting 4-month sputum conversion (likelihood ratios of 4.0 and 2.0,
      respectively) and was equivalent to phenotypic DST using the National Committee
      for Clinical Laboratory Standards (NCCLS)-approved agar proportion method for
      estimating MIC (likelihood ratio, 4.0). These results offer insight into
      mechanisms of resistance and cross-resistance among these agents and suggest that
      the development of rapid molecular tests to distinguish polymorphisms would
      significantly enhance clinical utility of this important class of second-line
      antituberculosis drugs.

PMID- 20032249
TI  - Prosthetic valve endocarditis due to Actinomyces neuii successfully treated with
      antibiotic therapy.
AB  - Endocarditis due to Actinomyces neuii is a rare disease, with only 14 reported
      cases. Recently, A. neuii was added to the list of species implicated in
      endocarditis of native valves. We now report the first case of prosthetic valve
      endocarditis and the first successful control of endocarditis caused by this
      organism without surgical intervention.

PMID- 20032250
TI  - Comparison of restriction fragment length polymorphism with the polymorphic
      guanine-cytosine-rich sequence and spoligotyping for differentiation of
      Mycobacterium tuberculosis isolates with five or fewer copies of IS6110.
AB  - The use of IS6110 as a marker for molecular epidemiological studies is limited
      when a Mycobacterium tuberculosis isolate has five or fewer copies of IS6110.
      Restriction fragment length polymorphism analysis with a highly polymorphic GC
      rich repetitive sequence located in the plasmid pTBN12 (PGRS RFLP) and
      spoligotyping (based on the polymorphism of the DR region) are two frequently
      used secondary typing methods. The aim of this study was to compare the
      performance of these two methods in a population-based study in San Francisco. We
      included all patients with culture-positive tuberculosis from 1999 to 2007 with
      IS6110 RFLP results presenting five or fewer bands. PGRS RFLP and spoligotyping
      were performed using standardized methods. We determined the concordance between
      the two methods regarding cluster status and the risk factors for an isolate to
      be in a cluster with each of the methods. Our data indicate that both methods had
      similar discriminatory power and that the risk factors associated with clustering
      by either method were the same. Although the cluster/unique status was concordant
      in 84% of the isolates, patients were clustered differently depending on the
      method. Therefore, the methods are not interchangeable, and the same method
      should be used for longitudinal studies.

PMID- 20032251
TI  - Identification of a variety of Staphylococcus species by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry.
AB  - Whole-cell fingerprinting by matrix-assisted laser desorption ionization-time-of
      flight mass spectrometry (MALDI-TOF MS) in combination with a dedicated
      bioinformatic software tool (MALDI Biotyper 2.0) was used to identify 152
      staphylococcal strains corresponding to 22 staphylococcal species. Spectra of the
      152 isolates, previously identified at the species level using a sodA gene-based
      oligonucleotide array, were analyzed against the main spectra of 3,030
      microorganisms. A total of 151 strains out of 152 (99.3%) were correctly
      identified at the species level; only one strain was identified at the genus
      level. The MALDI-TOF MS method revealed different clonal lineages of
      Staphylococcus epidermidis that were of either human or environmental origin,
      which suggests that the MALDI-TOF MS method could be useful in the profiling of
      staphylococcal strains. The topology of the dendrogram generated by the MALDI
      Biotyper 2.0 software from the spectra of 120 Staphylococcus reference strains
      (representing 36 species) was in general agreement with that inferred from the
      16S rRNA gene-based analysis. Our findings indicate that the MALDI-TOF MS
      technology, associated with a broad-spectrum reference database, is an effective
      tool for the swift and reliable identification of Staphylococci.

PMID- 20032252
TI  - Clonal dissemination of Klebsiella pneumoniae carbapenemase KPC-3 in Long Beach,
      California.
AB  - Carbapenems (CARBs) are the primary treatment for infections caused by extended
      spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae strains.
      Production of a serine carbapenemase, KPC, is increasing alarmingly in the United
      States and is probably contributing to CARB resistance rates. We describe the
      clinical and molecular characteristics of four infections caused by KPC-3 K.
      pneumoniae strains.

PMID- 20032253
TI  - Molecular characterization of extended-spectrum cephalosporinase-producing
      Salmonella enterica serovar Choleraesuis isolates from patients in Thailand and
      Denmark.
AB  - The objective of this study was to characterize extended-spectrum
      cephalosporinase (ESC)-producing isolates of Salmonella enterica serovar
      Choleraesuis recovered from patients in Thailand and Denmark. Twenty-four blood
      culture isolates from 22 patients were included in the study, of which 23
      isolates were recovered from 21 Thai patients during 2003, 2007, or 2008 and one
      isolate was recovered from a Danish traveler to Thailand. ESC production was
      confirmed in 13 out of the 24 isolates by MIC testing. Microarray and plasmid
      profiling (replicon typing and restriction fragment length polymorphism [RFLP])
      were used to characterize the genetic mechanisms of antimicrobial resistance in
      the 13 ESC-producing isolates. Pulsed-field gel electrophoresis (PFGE) and MIC
      testing were used to compare the clonality between the 13 ESC-producing isolates
      and the 11 non-ESC-producing isolates. Based on susceptibility patterns, the ESC
      producing isolates were more closely related than non-ESC-producing isolates.
      Microarray, PCR, plasmid profiling, and replicon typing revealed that the 13 ESC
      producing isolates harbored either bla(CMY-2) containing incA/C or bla(CTX-M-14)
      containing incFIIA, incFrepB, and an unknown replicon located on plasmids ranging
      in size from 75 to 200 kb. The RFLP and replicon typing clustered the isolates
      into four distinct groups. PFGE revealed 16 unique patterns and five clusters;
      each cluster contained two or three of the 24 isolates. The isolate from the
      Danish patient was indistinguishable from two Thai clinical isolates by PFGE.
      This study revealed the emergence of the bla(CTX-M-14) gene among several clones
      of Salmonella serovar Choleraesuis. Numerous plasmids were identified containing
      up to two different ESC genes and four distinct replicons. A "travel-associated"
      spread was confirmed. Overall, a high degree of clonal diversity between isolates
      resistant and susceptible to cephalosporins was observed. The findings represent
      a serious threat to public health for the Thai people and tourists.

PMID- 20032254
TI  - Corynebacterium accolens-associated pelvic osteomyelitis.
AB  - Corynebacterium accolens is a rare human pathogen. We encountered a case of C.
      accolens isolated from a thigh collection in a man with osteomyelitis of the
      adjacent pubic symphysis.

PMID- 20032255
TI  - Effect of carbon dioxide on broth microdilution susceptibility testing of
      Brucella spp.
AB  - Since some strains of Brucella species may require carbon dioxide for growth, a
      multilaboratory study was conducted to compare broth microdilution susceptibility
      results using ambient air (AA) and 5% CO2 incubation conditions. Six
      antimicrobial agents were tested against 39 Brucella isolates. Aminoglycoside
      MICs tended to be 1 log2 dilution higher in CO2 than in AA; tetracycline-class
      MICs to be 1 log2 dilution lower in CO2.

PMID- 20032256
TI  - Evaluation of diagnostic tests for Clostridium difficile infection.
AB  - We evaluated toxigenic Clostridium difficile detection by a lateral flow assay
      for antigen and toxin, an enzyme immunoassay, and two commercial PCR methods.
      Compared to the cell cytotoxicity neutralization assay and toxigenic culture,
      both toxin detection methods lacked sensitivity. PCR following combined antigen
      and toxin detection provided the most useful diagnostic information.

PMID- 20032257
TI  - Outbreaks of keratoconjunctivitis in a camel herd caused by a specific biovar of
      Moraxella canis.
AB  - Two tributyrin hydrolysis-negative Moraxella isolates obtained in cases of
      keratoconjunctivitis in Camelus dromedarius in the Canary Islands showed highest
      degrees of 16S rRNA gene sequence similarity to Moraxella canis. A level of DNA
      relatedness to the M. canis type strain of 79% confirmed the identity of the
      isolates as a tributyrin hydrolysis-negative biovar of M. canis.

PMID- 20032259
TI  - Metabolic syndrome among the young obese in the United Arab Emirates.
AB  - Obesity is the sixth major risk factor for the overall burden of disease
      globally, and is associated with a constellation of metabolic derangements
      starting early in life. Features of metabolic syndrome (MS) were assessed among
      obese young individuals in the UAE. Of the 260 obese young people screened, 44%
      were found to have MS. Prevalence of MS was more among boys than girls and there
      was a significant association with a positive family history of obesity, diabetes
      or hypertension. Subjective report of psychological distress was found in 95%,
      and significant depressive symptoms were present among three-quarters of those
      with MS. The prevalence and magnitude of obesity and its sequelae including MS is
      increasing world wide, and newly modernized countries are particularly at risk.
      Child health professionals must be aware of this and attempts should be made for
      early identification and necessary intervention including attention to
      psychological issues.

PMID- 20032258
TI  - First case of human infection due to Pseudomonas fulva, an environmental
      bacterium isolated from cerebrospinal fluid.
AB  - We report the first case of human infection due to Pseudomonas fulva. P. fulva
      caused acute meningitis following the placement of a drainage system in a 2-year
      old female. Additionally, the isolate displayed a VIM-2 carbapenemase in a class
      1 integron context.

PMID- 20032260
TI  - The soluble guanylyl cyclase inhibitor NS-2028 reduces vascular endothelial
      growth factor-induced angiogenesis and permeability.
AB  - Nitric oxide (NO) is known to promote vascular endothelial growth factor (VEGF)
      stimulated permeability and angiogenesis. However, effector molecules that
      operate downstream of NO in this pathway remain poorly characterized. Herein, we
      determined the effect of soluble guanylyl cyclase (sGC) inhibition on VEGF
      responses in vitro and in vivo. Treatment of endothelial cells (EC) with VEGF
      stimulated eNOS phosphorylation and cGMP accumulation; pretreatment with the sGC
      inhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS-2028)
      blunted cGMP levels without affecting VEGF-receptor phosphorylation. Incubation
      of cells with NS-2028 blocked the mitogenic effects of VEGF. In addition, cells
      in which sGC was inhibited exhibited no migration and sprouting in response to
      VEGF. To study the mechanisms through which NS-2028 inhibits EC migration, we
      determined the effects of alterations in cGMP levels on p38 MAPK. Initially, we
      observed that inhibition of sGC attenuated VEGF-stimulated activation of p38. In
      contrast, the addition of 8-Br-cGMP to EC stimulated p38 phosphorylation. The
      addition of cGMP elevating agents (BAY 41-2272, DETA NO and YC-1) enhanced EC
      migration. To test whether sGC also mediated the angiogenic effects of VEGF in
      vivo, we used the rabbit cornea assay. Animals receiving NS-2028 orally displayed
      a reduced angiogenic response to VEGF. As increased vascular permeability occurs
      prior to new blood vessel formation, we determined the effect of NS-2028 in
      vascular leakage. Using a modified Miles assay, we observed that NS-2028
      attenuated VEGF-induced permeability. Overall, we provide evidence that sGC
      mediates the angiogenic and permeability-promoting activities of VEGF, indicating
      the significance of sGC as a downstream effector of VEGF-triggered responses.

PMID- 20032261
TI  - Transient nitric oxide reduction induces permanent cardiac systolic dysfunction
      and worsens kidney damage in rats with chronic kidney disease.
AB  - Left ventricular systolic dysfunction (LVSD) in patients with chronic kidney
      disease (CKD) is associated with poorer prognosis. Because patients with CKD
      often exhibit progressively decreased nitric oxide (NO) availability and
      inhibition of NO production can reduce cardiac output, we hypothesized that loss
      of NO availability in CKD contributes to pathogenesis of LVSD. Subtotally
      nephrectomized (SNX) rats were treated with a low dose of the NO synthase
      inhibitor N(omega)-nitro-L-arginine (L-NNA; 20 mg/l water; SNX+L-NNA) and
      compared with relevant control groups. To study permanent changes separate from
      hemodynamic effects, L-NNA was stopped after week 8 and rats were followed up to
      week 15, until blood pressure was similar in SNX+L-NNA and SNX groups. To study
      effects of NO depletion alone, a control group with high-dose L-NNA (L-NNA-High:
      100 mg/l) was included. Mild systolic dysfunction developed at week 13 after SNX.
      In SNX+L-NNA, systolic function decreased by almost 50% already from week 4
      onward, together with markedly reduced whole body NO production and high
      mortality. In L-NNA-High, LVSD was not as severe as in SNX+L-NNA, and renal
      function was not affected. Both LVSD and NO depletion were reversible in L-NNA
      High after L-NNA was stopped, but both were persistently low in SNX+L-NNA.
      Proteinuria increased compared with rats with SNX, and glomerulosclerosis and
      cardiac fibrosis were worsened. We conclude that SNX+L-NNA induced accelerated
      and permanent LVSD that was functionally and structurally different from CKD or
      NO depletion alone. Availability of NO appears to play a pivotal role in
      maintaining cardiac function in CKD.

PMID- 20032262
TI  - Lower energy cost of skeletal muscle contractions in older humans.
AB  - Recent studies suggest that the cost of muscle contraction may be reduced in old
      age, which could be an important mediator of age-related differences in muscle
      fatigue under some circumstances. We used phosphorus magnetic resonance
      spectroscopy and electrically elicited contractions to examine the energetic cost
      of ankle dorsiflexion in 9 young (Y; 26 +/- 3.8 yr; mean +/- SD) and 9 older
      healthy men (O; 72 +/- 4.6). We hypothesized that the energy cost of twitch and
      tetanic contractions would be lower in O and that this difference would be
      greater during tetanic contractions at f(50) (frequency at 50% of peak force from
      force-frequency relationship) than at 25 Hz. The energy costs of a twitch (O =
      0.13 +/- 0.04 mM ATP/twitch, Y = 0.18 +/- 0.06; P = 0.045) and a 60-s tetanus at
      25 Hz (O = 1.5 +/- 0.4 mM ATP/s, Y = 2.0 +/- 0.2; P = 0.01) were 27% and 26%
      lower in O, respectively, while the respective force.time integrals were not
      different. In contrast, energy cost during a 90-s tetanus at f(50) (O = 10.9 +/-
      2.0 Hz, Y = 14.8 +/- 2.1 Hz; P = 0.002) was 49% lower in O (1.0 +/- 0.2 mM ATP/s)
      compared with Y (1.9 +/- 0.2; P < 0.001). Y had greater force potentiation during
      the f(50) protocol, which accounted for the greater age difference in energy cost
      at f(50) compared with 25 Hz. These results provide novel evidence of an age
      related difference in human contractile energy cost in vivo and suggest that
      intramuscular changes contribute to the lower cost of contraction in older
      muscle. This difference in energetics may provide an important mechanism for the
      enhanced fatigue resistance often observed in older individuals.

PMID- 20032264
TI  - Separate mechanisms cause anemia in ischemic vs. nonischemic murine heart
      failure.
AB  - In ischemic congestive heart failure (CHF), anemia is associated with poor
      prognosis. Whether anemia develops in nonischemic CHF is uncertain. The
      hematopoietic inhibitors TNF-alpha and nitric oxide (NO) are activated in
      ischemic CHF. We examined whether mice with ischemic or nonischemic CHF develop
      anemia and whether TNF-alpha and NO are involved. We studied mice (n = 7-9 per
      group) with CHF either due to myocardial infarction (MI) or to overexpression of
      the Ca(2+)-binding protein calsequestrin (CSQ) or to induced cardiac disruption
      of the sarcoplasmic reticulum Ca(2+)-ATPase 2 gene (SERCA2 KO). Hematopoiesis was
      analyzed by colony formation of CD34(+) bone marrow cells. Hemoglobin
      concentration was 14.0 +/- 0.4 g/dl (mean +/- SD) in controls, while it was
      decreased to 10.1 +/- 0.4, 9.7 +/- 0.4, and 9.6 +/- 0.3 g/dl in MI, CSQ, and
      SERCA2 KO, respectively (P < 0.05). Colony numbers per 100,000 CD34(+) cells in
      the three CHF groups were reduced to 33 +/- 3 (MI), 34 +/- 3 (CSQ), and 39 +/- 3
      (SERCA2 KO) compared with 68 +/- 4 in controls (P < 0.05). Plasma TNF-alpha
      nearly doubled in MI, and addition of anti-TNF-alpha antibody normalized colony
      formation. Inhibition of colony formation was completely abolished with blockade
      of endothelial NO synthase in CSQ and SERCA2 KO, but not in MI. In conclusion,
      the mechanism of anemia in CHF depends on the etiology of cardiac disease;
      whereas TNF-alpha impairs hematopoiesis in CHF following MI, NO inhibits blood
      cell formation in nonischemic murine CHF.

PMID- 20032263
TI  - Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation,
      pelvic sensitivity, and changes in urinary bladder function.
AB  - NGF has been suggested to play a role in urinary bladder dysfunction by mediating
      inflammation, as well as morphological and functional changes, in sensory and
      sympathetic neurons innervating the urinary bladder. To further explore the role
      of NGF in bladder sensory function, we generated a transgenic mouse model of
      chronic NGF overexpression in the bladder using the urothelium-specific uroplakin
      II (UPII) promoter. NGF mRNA and protein were expressed at higher levels in the
      bladders of NGF-overexpressing (NGF-OE) transgenic mice compared with wild-type
      littermate controls from postnatal day 7 through 12-16 wk of age. Overexpression
      of NGF led to urinary bladder enlargement characterized by marked nerve fiber
      hyperplasia in the submucosa and detrusor smooth muscle and elevated numbers of
      tissue mast cells. There was a marked increase in the density of CGRP- and
      substance P-positive C-fiber sensory afferents, neurofilament 200-positive
      myelinated sensory afferents, and tyrosine hydroxylase-positive sympathetic nerve
      fibers in the suburothelial nerve plexus. CGRP-positive ganglia were also present
      in the urinary bladders of transgenic mice. Transgenic mice had reduced urinary
      bladder capacity and an increase in the number and amplitude of nonvoiding
      bladder contractions under baseline conditions in conscious open-voiding
      cystometry. These changes in urinary bladder function were further associated
      with an increased referred somatic pelvic hypersensitivity. Thus, chronic
      urothelial NGF overexpression in transgenic mice leads to neuronal proliferation,
      focal increases in urinary bladder mast cells, increased urinary bladder reflex
      activity, and pelvic hypersensitivity. NGF-overexpressing mice may, therefore,
      provide a useful transgenic model for exploring the role of NGF in urinary
      bladder dysfunction.

PMID- 20032265
TI  - A new method for estimating smoking-attributable mortality in high-income
      countries.
AB  - BACKGROUND: Cigarette smoking is responsible for a massive loss of life in both
      developed and developing countries. This article develops an alternative to the
      Peto-Lopez method for estimating the number or fraction of smoking-attributable
      deaths in high-income countries. METHODS: We use lung cancer death rates as an
      indicator of the damage caused by smoking. Using administrative data for the
      population aged > or =50 years from 20 high-income countries in the period from
      1950 to 2006, we estimate a negative binomial regression model that predicts
      mortality from causes other than lung cancer as a function of lung cancer
      mortality and other variables. Using this regression model, we estimate smoking
      attributable deaths based on the difference between observed death rates from
      lung cancer and expected rates among non-smokers. RESULTS: Combining the
      estimated number of excess deaths from lung cancer with those from other causes,
      we find that among males in 1955 the smoking-attributable fraction was highest in
      Finland (18%); among women, no country exceeded 1%. By 2003, Hungary had the
      highest fraction of smoking-attributable deaths among males (32%), whereas the
      USA held that position among women (24%). Our estimates are remarkably similar to
      those produced by the Peto-Lopez method, a result that supports the validity of
      each approach. CONCLUSIONS: We provide a simple and straightforward method for
      estimating the proportion of deaths attributable to smoking in high-income
      countries. Our results demonstrate that smoking has played a central role in
      levels, trends and international differences in mortality over the past half
      century.

PMID- 20032266
TI  - A prospective study of body mass index and mortality in Bangladesh.
AB  - BACKGROUND: Body mass index (BMI) (kg/m(2)) has a U- or J-shaped relationship
      with all-cause mortality in Western and East Asian populations. However, this
      relationship is not well characterized in Bangladesh, where the BMI distribution
      is shifted towards lower values. METHODS: Using data on 11,445 individuals (aged
      18-75 years) participating in the Health Effects of Arsenic Longitudinal Study
      (HEALS) in Araihazar, Bangladesh, we prospectively examined associations of BMI
      (measured at baseline) with all-cause mortality during approximately 6 years of
      follow-up. We also examined this relationship within strata of key covariates
      (sex, age, smoking, education and arsenic exposure). Cox proportional hazards
      models adjusted for these covariates and BMI-related illnesses were used to
      estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for BMI
      categories defined by the World Health Organization. RESULTS: Low BMI was
      strongly associated with increased mortality in this cohort (P-trend < 0.0001).
      Severe underweight (BMI < 16 kg/m(2); HR 2.06, CI 1.53-2.77) and moderate
      underweight (16.0-16.9 kg/m(2); HR 1.39, CI 1.01-2.90) were associated with
      increased all-cause mortality compared with normal BMI (18.6-22.9 kg/m(2)). The
      highest BMI category (> or =23.0 kg/m(2)) did not show a clear association with
      mortality (HR 1.10, CI 0.77-1.53). The BMI-mortality association was stronger
      among individuals with <5 years of formal education (interaction P = 0.02).
      CONCLUSIONS: Underweight (presumably due to malnutrition) is a major determinant
      of mortality in the rural Bangladeshi population.

PMID- 20032268
TI  - Testing an integrative model of respect: implications for social engagement and
      well-being.
AB  - Prior research demonstrates that feelings of respect affect important aspects of
      group functioning and members' psychological well-being. One limitation is that
      respect has been variously defined as reflecting individuals' status in the
      group, degree to which they are liked by the group, and how fairly they are
      treated in interactions with group members. These different conceptions are
      integrated in the dual pathway model of respect. The authors tested the model's
      prediction that fair treatment from group members shapes attitudes toward the
      group and self via two distinct pathways: status and inclusion. Findings from a
      field study supported the model and yielded new insights: Whereas perceptions of
      status predicted social engagement, liking was more important in predicting well
      being (especially among dominant subgroups). Discussion focuses on the utility of
      the dual pathway model for understanding how respect perceptions are formed and
      how they affect the welfare of groups and individuals.

PMID- 20032267
TI  - Glutathione-S-transferase genes and asthma phenotypes: a Human Genome
      Epidemiology (HuGE) systematic review and meta-analysis including unpublished
      data.
AB  - BACKGROUND: Oxidative stress is thought to be involved in the pathogenesis of
      asthma. Glutathione-S-transferase (GST) enzymes, which play an important role in
      antioxidant defences, may therefore influence asthma risk. Two common deletion
      polymorphisms of GSTM1 and GSTT1 genes and the GSTP1 Ile105Val polymorphism have
      been associated with asthma in children and adults, but results are inconsistent
      across studies. METHODS: Systematic review and meta-analysis of the effects of
      GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with
      inclusion of unpublished data from three studies, including the large Avon
      Longitudinal Study of Parents and Children (ALSPAC). Random effect or fixed
      effect models were used as appropriate, and sensitivity analyses were performed
      to assess the impact of study characteristics and quality on pooled results.
      RESULTS: The meta-analyses of GSTM1 (n = 22 studies) and GSTT1 (n = 19) showed
      increased asthma risk associated with the null genotype, but there was extreme
      between-study heterogeneity and publication bias and the association disappeared
      when meta-analysis was restricted to the largest studies. Meta-analysis of GSTP1
      Ile105Val (n = 17) and asthma suggested a possible protective effect of the Val
      allele, but heterogeneity was extreme. Few studies evaluated wheezing and BHR and
      most reported no associations, although weak evidence was found for positive
      associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative
      association of GSTP1 Val allele with BHR. CONCLUSIONS: Our findings do not
      support a substantial role of GST genes alone in the development of asthma.
      Future studies of large size should focus on interactions of GST genes with
      environmental oxidative exposures and with other genes involved in antioxidant
      pathways. Quality of study conduct and reporting needs to be improved to increase
      credibility of the evidence accumulating over time.

PMID- 20032269
TI  - Sex buffers intimates against the negative implications of attachment insecurity.
AB  - Contextual models of relationships and recent theories of attachment system
      activation suggest that experiences that promote intimacy, such as sexual
      intercourse, may moderate the negative implications of attachment insecurity. In
      two independent studies, 207 couples reported their attachment insecurity, the
      frequency of their sexual intercourse over the past 30 days, their expectancies
      for their partner's availability, and their marital satisfaction, and in a 7-day
      diary they reported their daily sexual and relationship satisfaction and their
      expectancies for how satisfied they would be with their partners' availability
      the next day. Attachment avoidance was unrelated to marital satisfaction among
      spouses reporting more frequent sex, and attachment anxiety was unrelated to
      marital satisfaction among spouses reporting more daily sexual satisfaction. Both
      effects were mediated by expectancies for partner availability. These findings
      suggest that the effects of attachment insecurity are not immutable but vary
      according to the context of the relationship.

PMID- 20032270
TI  - When friends make you blue: the role of friendship contingent self-esteem in
      predicting self-esteem and depressive symptoms.
AB  - This research examines the role of friendship contingent self-esteem (FCSE), or
      self-esteem that is dependent on the quality of one's friendships, in predicting
      depressive symptoms. In Study 1, the authors developed a measure of FCSE. Both
      FCSE and others' approval correlated with self-esteem and depressive symptoms,
      but when entered simultaneously in a regression equation, only FCSE significantly
      predicted self-esteem and depressive symptoms. Study 2 showed that dependency and
      close friendship competence predicted depressive symptoms only for those high in
      FCSE. In Study 3, a diary study, FCSE predicted self-esteem instability. Self
      esteem instability, in turn, predicted depressive symptoms. Furthermore, a three
      way interaction of rumination, FCSE, and the valence of the event predicted
      momentary self-esteem. Findings are discussed with regard to the importance of
      considering FCSE when investigating interpersonal risk for depression.

PMID- 20032271
TI  - Not so fast: the (not-quite-complete) dissociation between accuracy and
      confidence in thin-slice impressions.
AB  - After decades of research highlighting the fallibility of first impressions,
      recent years have featured reports of valid impressions based on surprisingly
      limited information, such as photos and short videos.Yet beneath mean levels of
      accuracy lies tremendous variance-some snap judgments are well-founded, others
      wrongheaded. An essential question for perceivers, therefore, is whether and when
      to trust their initial intuitions about others. In three studies of first
      impressions based on photos and videos, the authors examined accuracy for Big
      Five trait judgments as well as corresponding reports of confidence. Overall,
      perceivers showed a limited ability to intuit which of their impressions were
      more accurate than others, although a curvilinear effect emerged: In the
      relatively few cases where perceivers reported an absolute lack of confidence,
      their accuracy was indeed comparatively low. Across the studies, judgment
      confidence was shaped by sources at the judgment level and the judge level that
      were unrelated to accuracy.

PMID- 20032272
TI  - The role of need satisfaction in self-concealment and well-being.
AB  - The present research tests a model derived from self-determination theory to
      explain why self-concealment (the tendency to keep distressing personal
      information secret) is associated with negative well-being outcomes. Two studies
      tested a model in which self-concealment predicts the thwarting of basic needs
      for autonomy, competence, and relatedness, which then results in negative
      psychological outcomes. Study 1 involved a cross-sectional design. Structural
      equation modeling analyses revealed that the model provided an acceptable fit to
      the data. Study 2 involved a multilevel design. Participants completed daily
      measures of self-concealment, need satisfaction, and well-being over 16 days.
      Results supported the proposed mediation model. Furthermore, the associations
      between daily self-concealment, daily need satisfaction, and daily well-being
      were independent of trait self-concealment. Overall, the findings suggest that
      concealing personal distressing information is detrimental to the satisfaction of
      basic psychological needs, which in turn predicts negative well-being.

PMID- 20032273
TI  - Capitalizing on multiple social identities to prevent stereotype threat: the
      moderating role of self-esteem.
AB  - One troubling aspect of membership in a stigmatized group is that negative
      stereotypes about the group's performance affect one's personal performance
      (i.e., stereotype threat). Women who are made aware of the negative stereotype
      that "women are bad at math" perform worse than women who are not made aware of
      this stereotype. However, women can use an "escape hatch" to avoid stereotype
      threat by identifying with another social identity (i.e., college students) that
      has positive stereotypes for math performance and having greater feelings of self
      worth. This research shows that women who had greater self-esteem and were
      presented with an alternative, positive social identity were buffered from
      stereotype threat by eliminating working memory decrements responsible for poor
      math performance. Women lower in self-esteem, however, did not benefit from a
      positive, alternative social identity when it was available and thus fell prey to
      stereotype-based working memory and performance decrements.

PMID- 20032274
TI  - Hypoglycemia aggravates critical illness-induced neurocognitive dysfunction.
AB  - OBJECTIVE Tight glycemic control (TGC) in critically ill patients is associated
      with an increased risk of hypoglycemia. Whether those short episodes of
      hypoglycemia are associated with adverse morbidity and mortality is a matter of
      discussion. Using a case-control study design, we investigated whether
      hypoglycemia under TGC causes permanent neurocognitive dysfunction in patients
      surviving critical illness. RESEARCH DESIGN AND METHODS From our patient data
      management system, we identified adult survivors treated for >72 h in our
      surgical intensive care unit (ICU) between 2004 and 2007 (n = 4,635) without a
      history of neurocognitive dysfunction or structural brain abnormalities who
      experienced at least one episode of hypoglycemia during treatment (hypo group) (n
      = 37). For each hypo group patient, one patient stringently matched for
      demographic- and disease-related data were identified as a control subject. We
      performed a battery of neuropsychological tests investigating five areas of
      cognitive functioning in both groups at least 1 year after ICU discharge. Test
      results were compared with data from healthy control subjects and between groups.
      RESULTS Critical illness caused neurocognitive dysfunction in all tested domains
      in both groups. The dysfunction was aggravated in hypo group patients in one
      domain, namely that of visuospatial skills (P < 0.01). Besides hypoglycemia, both
      hyperglycemia (r = -0.322; P = 0.005) and fluctuations of blood glucose (r = 
      0.309; P = 0.008) were associated with worse test results in this domain.
      CONCLUSIONS Hypoglycemia was found to aggravate critical illness-induced
      neurocognitive dysfunction to a limited, but significant, extent; however, an
      impact of hyperglycemia and fluctuations of blood glucose on neurocognitive
      function cannot be excluded.

PMID- 20032275
TI  - An internet-based program to improve self-management in adolescents with type 1
      diabetes.
AB  - OBJECTIVE To report results from YourWay, an Internet-based self-management
      intervention for adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS A
      total of 72 adolescents with type 1 diabetes, ages 13-17 years, were randomized
      to a usual-care-plus-Internet support or a usual-care group. The intervention was
      designed to enhance problem-solving barriers to self-management. A1C was obtained
      from medical records, and problem-solving and self-management were obtained via
      adolescent report. RESULTS Group differences were not statistically significant
      using intent-to-treat analyses. Using as-treated analyses, adolescents in the
      treatment condition showed statistically significant improvement in self
      management (d = 0.64; P = 0.02) and important improvements in problem-solving (d
      = 0.30; P = 0.23) and A1C (d = -0.28; P = 0.27). Mean A1C for the intervention
      group remained constant (-0.01%), while the control group increased (0.33%).
      CONCLUSIONS This brief trial suggests that self-management support delivered
      through a secure website may improve self-management and offset typical decreases
      in adolescent glycemic control.

PMID- 20032276
TI  - Antidepressant pharmacotherapy in adults with type 2 diabetes: rates and
      predictors of initial response.
AB  - OBJECTIVE Initial treatment with antidepressant medication is insufficiently
      effective in some patients with type 2 diabetes, and factors predicting treatment
      outcome are poorly understood. RESEARCH DESIGN AND METHODS Aggregate data from
      two published trials were analyzed to determine the rates and predictors of
      response to antidepressant pharmacotherapy in adults with type 2 diabetes using
      conventional markers of initial treatment outcome (improvement, response, partial
      remission, and remission). Three hundred eighty-seven patients who received up to
      16 weeks of open-label, acute-phase treatment using bupropion (n = 93) or
      sertraline (n = 294) were studied. Logistic regression was used to identify
      predictors of poor treatment outcome. Candidate predictors included age, race,
      sex, initial Beck Depression Inventory (iBDI) score, treatment received
      (sertraline or bupropion), family history of depression, extant diabetes
      complications (eDC), and A1C level. RESULTS Of 387 patients initiated on
      treatment, 330 (85.3%) met criteria for improvement, 232 (59.9%) for response,
      207 (53.5%) for partial remission, and 179 (46.3%) for full remission.
      Significant independent predictors of poor outcome included eDC (for no
      improvement); sertraline treatment, eDC, and younger age (for nonresponse);
      sertraline treatment, eDC, and higher iBDI (for failure to partially remit); and
      younger age and higher iBDI (for failure to fully remit). Higher pain scores
      predicted three of the four markers of poor outcome in the subset with pain data.
      CONCLUSIONS In patients with type 2 diabetes, poor initial response to
      antidepressant medication is predicted by multiple factors. Auxiliary treatment
      of pain and impairment may be required to achieve better outcomes.

PMID- 20032277
TI  - A1C but not serum glycated albumin is elevated because of iron deficiency in late
      pregnancy in diabetic women.
AB  - OBJECTIVE We have already reported that A1C is elevated because of iron
      deficiency in late pregnancy among nondiabetic pregnant women. This report
      examined whether the same phenomenon is observed in pregnant women with diabetes.
      RESEARCH DESIGN AND METHODS This longitudinal study was conducted in 17 pregnant
      women with diabetes (20-35 weeks of pregnancy). A1C, serum glycated albumin,
      erythrocyte indexes, and iron metabolism indexes were measured. RESULTS A1C
      levels were significantly increased in late pregnancy, whereas serum glycated
      albumin showed no significant changes. Glycated albumin/A1C ratio, mean
      corpuscular hemoglobin, serum transferrin saturation, and serum ferritin were
      significantly decreased in late pregnancy. Serum transferrin saturation showed a
      significant positive correlation with glycated albumin/A1C ratio. CONCLUSIONS A1C
      levels, but not serum glycated albumin levels, are elevated in late pregnancy
      because of iron deficiency in diabetic women. Serum glycated albumin may offer an
      adequate marker for glycemic control during pregnancy.

PMID- 20032278
TI  - Brief screening tool for disordered eating in diabetes: internal consistency and
      external validity in a contemporary sample of pediatric patients with type 1
      diabetes.
AB  - OBJECTIVE To update and validate a diabetes-specific screening tool for
      disordered eating (the Diabetes Eating Problem Survey [DEPS]) in contemporary
      youth with type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 112 youth with
      type 1 diabetes, ages 13-19 years, completed the DEPS. Higher scores on the DEPS
      indicate more disordered eating behaviors. Youth and their parents also completed
      additional surveys to examine diabetes-specific family conflict, negative affect
      related to blood glucose monitoring, youth quality of life, and diabetes burden.
      Clinicians provided data on height, weight, A1C, and insulin dosing. The DEPS was
      revised into a shorter, updated measure and validated. RESULTS The revised 16
      item DEPS (DEPS-R) displayed excellent internal consistency (Cronbach's alpha =
      0.86). Construct validity was demonstrated by positive correlations with zBMI (P
      = 0.01), A1C (P = 0.001), diabetes-specific family conflict (P < 0.005), youth
      negative affect around blood glucose monitoring (P = 0.001), parental diabetes
      specific burden (P = 0.0005), and negative correlations with frequency of blood
      glucose monitoring (P = 0.03) and quality of life (P < or = 0.002). External
      validity was confirmed against clinician report of insulin restriction.
      CONCLUSIONS The DEPS-R is a 16-item diabetes-specific self-report measure of
      disordered eating that can be completed in <10 min. It demonstrated excellent
      internal consistency, construct validity, and external validity in this
      contemporary sample of youth with type 1 diabetes. Future studies should focus on
      using the DEPS-R to identify high-risk populations for prevention of and early
      intervention for disordered eating behaviors.

PMID- 20032279
TI  - Missed insulin boluses for snacks in youth with type 1 diabetes.
AB  - OBJECTIVE To evaluate the effects of missed insulin boluses for snacks in youth
      with type 1 diabetes. RESEARCH DESIGN AND METHODS Three months of simultaneous
      continuous subcutaneous insulin infusion and continuous glucose monitoring data
      from nine subjects were retrospectively evaluated. Glucose excursions between
      1330 and 1700 h were defined as relating to snacks with insulin or snacks with no
      insulin administered. Area under the curve >180 mg/dl (AUC >180), average Delta
      glucose, and rate of change were analyzed and compared within and between groups.
      RESULTS A total of 94 snacks without insulin and 101 snacks with insulin were
      analyzed. Snacks without insulin had significantly higher log (AUC >180 + 1)
      (1.26 vs. 0.44 mg/dl per event; P < 0.001), Delta glucose (114 vs. 52 mg/dl; P <
      0.001), and average rate of change (1.3 vs. 1.1 mg/dl per minute; P < 0.001).
      CONCLUSIONS This study shows that afternoon snacks without insulin boluses are
      common and result in significantly higher glucose excursions than snacks with
      insulin administration.

PMID- 20032280
TI  - Estimates of insulin sensitivity using glucose and C-Peptide from the
      hyperglycemia and adverse pregnancy outcome glucose tolerance test.
AB  - OBJECTIVE To determine if glucose and C-peptide values obtained as part of the
      Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study could be used to
      estimate insulin sensitivity during late pregnancy. RESEARCH DESIGN AND METHODS A
      total of 78 women enrolled in the HAPO study were recruited for this ancillary
      study. Venous plasma samples were drawn after an 8- to 10-h fast (time 0) and at
      30, 60, 90, and 120 min after a 75-g glucose challenge, which was performed at 24
      32 weeks' gestation. Samples were analyzed for plasma glucose, insulin, and C
      peptide. Insulin sensitivity was estimated using the established Matsuda and
      DeFronzo insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)).
      Insulin sensitivity was also calculated from two other commonly used indexes of
      insulin sensitivity (that for homeostasis model assessment [IS(HOMA)] and that
      for quantitative insulin sensitivity check index [IS(QUICKI)]). A new insulin
      sensitivity index was calculated using the glucose and C-peptide concentrations
      at 0 and 60 min to derive IS(HOMA C-pep), IS(QUICKI C-pep), and IS(OGTT C-pep).
      These indexes were then correlated with insulin sensitivity estimated from the
      IS(OGTT). RESULTS The strongest correlation with the IS(OGTT) was obtained for
      IS(OGTT C-pep) (r = 0.792, P < 0.001). Further, the correlations of IS(HOMA) (C
      pep) and IS(QUICKI C-pep) with IS(OGTT) were also significant (r = 0.676, P <
      0.001 and r = 0.707, P < 0.001, respectively). CONCLUSIONS These data suggest
      that calculated IS(OGTT C-pep) is an excellent predictor of insulin sensitivity
      in pregnancy and can be used to estimate insulin sensitivity in over 25,000 women
      participating in the HAPO study.

PMID- 20032281
TI  - Subjects with early-onset type 2 diabetes show defective activation of the
      skeletal muscle PGC-1{alpha}/Mitofusin-2 regulatory pathway in response to
      physical activity.
AB  - OBJECTIVE Type 2 diabetes is associated with insulin resistance and skeletal
      muscle mitochondrial dysfunction. We have found that subjects with early-onset
      type 2 diabetes show incapacity to increase Vo(2max) in response to chronic
      exercise. This suggests a defect in muscle mitochondrial response to exercise.
      Here, we have explored the nature of the mechanisms involved. RESEARCH DESIGN AND
      METHODS Muscle biopsies were collected from young type 2 diabetic subjects and
      obese control subjects before and after acute or chronic exercise protocols, and
      the expression of genes and/or proteins relevant to mitochondrial function was
      measured. In particular, the regulatory pathway peroxisome proliferator-activated
      receptor gamma coactivator (PGC)-1alpha/mitofusin-2 (Mfn2) was analyzed. RESULTS
      At baseline, subjects with diabetes showed reduced expression (by 26%) of the
      mitochondrial fusion protein Mfn2 and a 39% reduction of the alpha-subunit of ATP
      synthase. Porin expression was unchanged, consistent with normal mitochondrial
      mass. Chronic exercise led to a 2.8-fold increase in Mfn2, as well as increases
      in porin, and the alpha-subunit of ATP synthase in muscle from control subjects.
      However, Mfn2 was unchanged after chronic exercise in individuals with diabetes,
      whereas porin and alpha-subunit of ATP synthase were increased. Acute exercise
      caused a fourfold increase in PGC-1alpha expression in muscle from control
      subjects but not in subjects with diabetes. CONCLUSIONS Our results demonstrate
      alterations in the regulatory pathway that controls PGC-1alpha expression and
      induction of Mfn2 in muscle from patients with early-onset type 2 diabetes.
      Patients with early-onset type 2 diabetes display abnormalities in the exercise
      dependent pathway that regulates the expression of PGC-1alpha and Mfn2.

PMID- 20032282
TI  - Trends of earlier and later responses of C-peptide to oral glucose challenges
      with progression to type 1 diabetes in diabetes prevention trial-type 1
      participants.
AB  - OBJECTIVE We studied the C-peptide response to oral glucose with progression to
      type 1 diabetes in Diabetes Prevention Trial-Type 1 (DPT-1) participants.
      RESEARCH DESIGN AND METHODS Among 504 DPT-1 participants <15 years of age,
      longitudinal analyses were performed in 36 progressors and 80 nonprogressors.
      Progressors had oral glucose tolerance tests (OGTTs) at baseline and every 6
      months from 2.0 to 0.5 years before diagnosis; nonprogressors had OGTTs over
      similar intervals before their last visit. Sixty-six progressors and 192
      nonprogressors were also studied proximal to and at diagnosis. RESULTS The 30-0
      min C-peptide difference from OGTTs performed 2.0 years before diagnosis in
      progressors was lower than the 30-0 min C-peptide difference from OGTTs performed
      2.0 years before the last visit in nonprogressors (P < 0.01) and remained lower
      over time. The 90-60 min C-peptide difference was positive at every OGTT before
      diagnosis in progressors, whereas it was negative at every OGTT before the last
      visit in nonprogressors (P < 0.01 at 2.0 years). The percentage whose peak C
      peptide occurred at 120 min was higher in progressors at 2.0 years (P < 0.05);
      this persisted over time (P < 0.001 at 0.5 years). However, the peak C-peptide
      levels were only significantly lower at 0.5 years in progressors (P < 0.01). The
      timing of the peak C-peptide predicted type 1 diabetes (P < 0.001); peak C
      peptide levels were less predictive (P < 0.05). CONCLUSIONS A decreased early C
      peptide response to oral glucose and an increased later response occur at least 2
      years before the diagnosis of type 1 diabetes.

PMID- 20032284
TI  - Predicting gene networks in human oocyte meiosis.

PMID- 20032283
TI  - Toxic effects of hyperglycemia are mediated by the hexosamine signaling pathway
      and o-linked glycosylation in early mouse embryos.
AB  - Maternal hyperglycemia is believed to be the metabolic derangement associated
      with both early pregnancy loss and congenital malformations in a diabetic
      pregnancy. Using an in vitro model of embryo exposure to hyperglycemia, this
      study questioned if increased flux through the hexosamine signaling pathway
      (HSP), which results in increased embryonic O-linked glycosylation (O
      GlcNAcylation), underlies the glucotoxic effects of hyperglycemia during early
      embryogenesis. Mouse zygotes were randomly allocated to culture treatment groups
      that included no glucose (no flux through HSP), hyperglycemia (27 mM glucose,
      excess flux), 0.2 mM glucosamine (GlcN) in the absence of glucose (HSP flux
      alone), and O-GlcNAcylation levels monitored immunohistochemically. The impact of
      HSP manipulation on the first differentiation in development, blastocyst
      formation, was assessed, as were apoptosis and cell number in individual embryos.
      The enzymes regulating O-GlcNAcylation, and therefore hexosamine signaling, are
      the beta-linked-O-GlcNAc transferase (OGT) and an O-GlcNAc-selective beta-N
      acetylglucosaminidase (O-GlcNAcase). Inhibition of these enzymes has a negative
      impact on blastocyst formation, demonstrating the importance of this signaling
      system to developmental potential. The ability of the OGT inhibitor benzyl-2
      acetamido-2-deoxy-alpha-D-galactopyranoside (BADGP) to reverse the glucotoxic
      effects of hyperglycemia on these parameters was also sought. Excess HSP flux
      arising from a hyperglycemic environment or glucosamine supplementation reduced
      cell proliferation and blastocyst formation, confirming the criticality of this
      signaling pathway during early embryogenesis. Inhibition of OGT using BADGP
      blocked the negative impact of hyperglycemia on blastocyst formation, cell
      number, and apoptosis. Our results suggest that dysregulation of HSP and O
      GlcNAcylation is the mechanism by which the embryotoxic effects of hyperglycemia
      are manifested during preimplantation development.

PMID- 20032285
TI  - Arthrofibrosis after surgical fixation of tibial eminence fractures in children
      and adolescents.
AB  - BACKGROUND: Tibial eminence fractures are rare injuries in children and
      adolescents. Displaced fractures require reduction and fixation. Operative
      stabilization can be accomplished with either open or arthroscopic reduction and
      fixation. Whereas loss of extension has been reported, there are no reports in
      the literature that quantify loss of motion or provide guidance for treatment.
      PURPOSE: To report a series of patients who developed knee stiffness after
      operative treatment for displaced tibial eminence fractures. STUDY DESIGN: Case
      series; Level of evidence, 4. METHODS: Review of medical records and imaging
      studies of pediatric patients with displaced tibial eminence fractures who
      developed arthrofibrosis after surgical intervention. RESULTS: Thirty-two
      patients were identified. Twenty-four required reoperation for loss of flexion (n
      = 9), loss of extension (n = 4), or both (n = 11). Manipulation under anesthesia
      resulted in distal femoral fractures and subsequent growth arrest in 3 patients.
      Twenty-nine patients were able to achieve near full knee motion at final follow
      up. CONCLUSIONS: Children with tibial spine fractures are at risk for
      arthrofibrosis. Stabilization of the fracture is important to allow early
      postoperative rehabilitation. Should stiffness occur, manipulation of the knee
      should be performed only in conjunction with lysis of adhesions.

PMID- 20032286
TI  - Predictors of response to intervention of word reading fluency in Dutch.
AB  - The objective of this study was to investigate the contribution of rapid digit
      naming, phonological memory, letter sound naming, and orthographic knowledge to
      the prediction of responsiveness to a school-based, individual intervention of
      word reading fluency problems of 122 Dutch second and third graders whose reading
      scores were below the 10th percentile in comparison with the normative group.
      Degree of responsiveness was determined by comparison of a pre- and posttest
      measure of word reading fluency with a 6-month interval. At posttest, 38% of the
      children had improved their reading scores above the 10th percentile. Maintenance
      scores revealed no significant growth on average, confirming that word reading
      fluency skills of poor readers are hard to remediate. Except rapid digit naming,
      none of the measures predicted responsiveness after controlling for the
      autoregressive effect of initial performance on fluency of word reading. A large
      part of the variance remained unexplained, supporting the advantage of a response
      to-intervention approach above traditional psychometric testing to identify
      severe reading disabilities.

PMID- 20032287
TI  - Is there a link between cancer and Alzheimer disease?

PMID- 20032288
TI  - Cancer linked to Alzheimer disease but not vascular dementia.
AB  - OBJECTIVE: To investigate whether cancer is associated with Alzheimer disease
      (AD) and vascular dementia (VaD). METHODS: Cox proportional hazards models were
      used to test associations between prevalent dementia and risk of future cancer
      hospitalization, and associations between prevalent cancer and risk of subsequent
      dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a
      prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean
      of 5.4 years for dementia and 8.3 years for cancer. RESULTS: The presence of any
      AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval
      [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95% CI = 0.12-0.86) was associated with
      a reduced risk of future cancer hospitalization, adjusted for demographic
      factors, smoking, obesity, and physical activity. No significant associations
      were found between dementia at baseline and rate of cancer hospitalizations for
      participants with diagnoses of VaD. Prevalent cancer was associated with reduced
      risk of any AD (HR = 0.72; 95% CI = 0.52-0.997) and pure AD (HR = 0.57; 95% CI =
      0.36-0.90) among white subjects after adjustment for demographics, number of APOE
      epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the
      opposite association was found among minorities, but the sample size was too
      small to provide stable estimates. No significant association was found between
      cancer and subsequent development of VaD. CONCLUSIONS: In white older adults,
      prevalent Alzheimer disease (AD) was longitudinally associated with a reduced
      risk of cancer, and a history of cancer was associated with a reduced risk of AD.
      Together with other work showing associations between cancer and Parkinson
      disease, these findings suggest the possibility that cancer is linked to
      neurodegeneration.

PMID- 20032289
TI  - Subclinical myocardial necrosis and cardiovascular risk in stable patients
      undergoing elective cardiac evaluation.
AB  - OBJECTIVE: The presence of subclinical myocardial necrosis as a prodrome to
      longer-term adverse cardiac event risk has been debated. The debate has focused
      predominantly within patients with acute coronary syndrome, and on issues of
      troponin assay variability and accuracy of detection, rather than on the clinical
      significance of the presence of subclinical myocardial necrosis (ie, "troponin
      leak") within stable cardiac patients. Herein, we examine the relationship
      between different degrees of subclinical myocardial necrosis and long-term
      adverse clinical outcomes within a stable cardiac patient population with
      essentially normal renal function. METHODS AND RESULTS: Sequential consenting
      patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing
      elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels
      below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL)
      were evaluated. The relationship of subclinical myocardial necrosis with incident
      major adverse cardiovascular events (defined as any death, myocardial infarction,
      or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008
      ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis
      were observed frequently within the cohort (34% and 18%, respectively). A linear
      relationship was observed between the magnitude of subclinical myocardial
      necrosis and risk of 3-year incident major adverse cardiovascular events,
      particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95%
      confidence interval, 2.4-3.8), even after adjustment for traditional risk
      factors, C-reactive protein, and creatinine clearance. The presence of
      subclinical myocardial necrosis was associated with elevations in acute phase
      proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in
      systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no
      significant associations with multiple specific measures of oxidant stress, and
      showed borderline associations with myeloperoxidase, a marker of leukocyte
      activation. CONCLUSIONS: In stable cardiology patients, prodromal subclinical
      myocardial necrosis is associated with substantially higher long-term risk for
      major adverse cardiovascular events. The underlying mechanisms contributing to
      this minimal troponin leak phenomenon warrants further investigation.

PMID- 20032290
TI  - Activation of hemostasis and decline in cognitive function in older people.
AB  - OBJECTIVE: To determine whether activation of hemostatic function (thrombosis and
      fibrinolysis) is associated with cognitive decline in older people. METHODS AND
      RESULTS: We studied 5804 people (age, 70-82 years) in the Prospective Study of
      Pravastatin in the Elderly at Risk (PROSPER). Mean follow-up was 3.2 years,
      including annual measurement of speed of information processing (letter, digit
      coding, and Stroop), verbal memory (picture-word naming), and basic and
      instrumental activities of daily living. Raised levels of markers of thrombin
      generation (d-dimer and prothrombin fragment 1+2) were associated independently
      with increased rate of cognitive decline (eg, Stroop increased by 4.44 s [SEM,
      0.68] in bottom tertile of d-dimer compared to 5.46 [SEM, 0.71] in highest
      tertile; P<0.05) and deterioration in activities of daily living. This increased
      rate of decline was attenuated but not removed when subjects with incident
      nonfatal stroke were omitted from the analysis. It also persisted when
      adjustments were made for inflammation (C-reactive protein and IL-6).
      CONCLUSIONS: Older patients with increased markers of thrombin generation (d
      dimer and prothrombin fragment 1+2) are at increased risk for cognitive decline
      and deterioration in ability to perform activities of daily living. This is
      likely attributable to increased risk of cerebral ischemic damage (including
      covert disease) associated with prothrombotic states.

PMID- 20032291
TI  - Association of plasma sphingomyelin levels and incident coronary heart disease
      events in an adult population: Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: A high plasma sphingomyelin level has been associated with subclinical
      atherosclerosis, coronary artery disease, and worse prognosis in subjects with
      acute coronary syndromes. We wanted to assess the predictive value of plasma
      sphingomyelin levels for incident coronary heart disease (CHD) events in the
      Multi-Ethnic Study of Atherosclerosis. METHODS AND RESULTS: The plasma
      sphingomyelin level was measured in 6809 of 6814 subjects (age, mean+/-SD, 62.2+/
      10.2 years) participating in the Multi-Ethnic Study of Atherosclerosis, a
      population-based cohort study of adults free of clinical cardiovascular disease
      at baseline recruited at 6 clinic sites in the United States. The subjects
      consisted of 52.8% females, 38.5% whites, 11.8% Chinese, 27.8% blacks, and 21.9%
      Hispanics. Cox proportional hazard analysis was used to examine the association
      between plasma sphingomyelin level and 5 years of adjudicated incident CHD
      events, including myocardial infarction, resuscitated cardiac arrest, angina, CHD
      related death, and revascularization (coronary artery bypass grafting or
      percutaneous transluminal coronary angioplasty). The mean+/-SD plasma
      sphingomyelin level was 48.0+/-16.0 mg/dL. A total of 189 subjects had an
      adjudicated CHD event during the 5 years of follow-up. In the Kaplan-Meier
      analysis, subjects with a plasma sphingomyelin level higher than the sex-specific
      median had a similar event-free survival rate compared with subjects with a
      plasma sphingomyelin level at or less than the sex-specific median (97.16% versus
      97.00%; log rank P=0.71). In the univariate Cox proportional hazard analysis, the
      plasma sphingomyelin level was not a predictor of an incident CHD event (hazard
      ratio, 0.992 [0.982-1.004]; P=0.09). In our multistage multivariate Cox
      proportional hazard models, a higher plasma sphingomyelin level had a modest
      negative association with incident CHD events when total cholesterol, high
      density lipoprotein, and triglycerides were included in the model (hazard ratio,
      0.985 [0.973-0.996]; P=0.008) and also in our full model after adjusting for age,
      sex, total cholesterol, high-density lipoprotein, triglycerides, diabetes
      mellitus, cigarette smoking, systolic and diastolic blood pressure, medication
      use for blood pressure, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitor use (hazard ratio, 0.984 [0.973-0.996]; P=0.002). In other models, the
      plasma sphingomyelin level was not associated with incident CHD events.
      CONCLUSIONS: A high plasma sphingomyelin level is not associated with an
      increased risk of incident CHD in population-based adults free of clinical
      cardiovascular disease at baseline.

PMID- 20032292
TI  - Uncoupling protein-2 negatively regulates polymorphonuclear leukocytes chemotaxis
      via modulating [Ca2+] influx.
AB  - OBJECTIVE: Previous studies demonstrated that uncoupling protein 2 (UCP2) plays a
      negative role in modulating leukocyte inflammatory responses. The mechanism
      underneath the role of UCP2 in modulating leukocyte inflammatory responses,
      however, is incompletely understood. Here, we investigated the effect of UCP2 in
      polymorphonuclear leukocyte (PMN) chemotaxis. METHODS AND RESULTS: First, we
      assessed PMN chemotaxis in zymosan-induced murine peritonitis and found that
      UCP2(-/-) mice had significantly more migrated PMN in peritoneal lavage compared
      to their wild-type littermates. In vitro transmigration assays using isolated PMN
      also showed that PMN from UCP2(-/-) mice migrated faster than those from wild
      type mice in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP). Second,
      in supporting an inhibitory role of UCP2 in PMN transmigration, migrated PMN had
      a decreased UCP2 expression compared to nonmigrated PMN. In contrast, in
      streptozotocin-induced diabetic mice in which UCP2 expression was enhanced, PMN
      chemotaxis was reduced. Third, comparing to UCP2(+/+) PMN, UCP2(-/-) PMN had a
      stronger upregulation of fMLP-induced surface CD11b/CD18 and CD11a/CD18. Finally,
      UCP2(-/-) PMN showed a quicker and larger fMLP-triggered intracellular calcium
      mobilization compared to UCP2(+/+) PMN. CONCLUSIONS: Our study demonstrates that
      UCP2 serves as a brake in controlling PMN chemotaxis and that the effect of UCP2
      on PMN chemotaxis may be through modulating calcium influx.

PMID- 20032293
TI  - Human embryonic stem cells suppress T cell responses via arginase I-dependent
      mechanism.
AB  - Human embryonic stem cells (hESCs) can proliferate extensively in culture and
      give rise to progeny of the three germ layers. Several reports suggested that
      mouse and hESCs may attenuate immune responses. In this study, we focused on the
      mechanism by which hESCs inhibit T cell responses. Using coculture experiments,
      we demonstrate that hESCs inhibit cytokine secretion and T cell proliferation in
      response to potent T cell activators. Furthermore, we show that hESCs
      downmodulate the TCR-associated CD3-zeta chain. These effects are maintained when
      hESCs are replaced by their conditioned media and can be restored by the addition
      of L-arginine to hESC-conditioned media or by treatment of hESCs with a specific
      arginase inhibitor. Moreover, we show arginase-I expression and activity in
      hESCs. We further demonstrate that mouse ESCs (mESCs) similarly inhibit T cell
      activation via arginase I, suggesting an evolutionary conserved mechanism of T
      cell suppression by ESCs. In addition, we demonstrate that arginase I expression
      is not limited to ESCs in culture, but can also be detected in the inner cell
      mass and the trophectoderm of preimplantation mouse embryos and hESC-derived
      trophectoderm cells. Finally, T cells infiltrating ESC-derived teratomas have
      significantly lower levels of CD3-zeta chain. Collectively, the data indicate a
      role for ESC-arginase I activity in the attenuation of T cell activation.

PMID- 20032294
TI  - Structural basis for the blockage of IL-2 signaling by therapeutic antibody
      basiliximab.
AB  - IL-2 signaling plays a central role in the initiation and activation of immune
      responses. Correspondingly, blockage of this pathway leads to inhibition of the
      immune system and would provide some therapeutic benefits. Basiliximab
      (Simulect), a therapeutic mAb drug with specificity against IL-2R alpha of T
      cells, was approved by U.S. Food and Drug Administration in 1998. It has been
      proven to be effective in the suppression of the IL-2 pathway and hence has been
      widely used to prevent allograft rejection in organ transplantation, especially
      in kidney transplants. In this study, we report the crystal structure of the
      basiliximab Fab in complex with the ectodomain of IL-2R alpha at 2.9 A
      resolution. In the complex structure, the Fab interacts with IL-2R alpha with
      extensive hydrophobic and hydrophilic interactions, accounting for a high binding
      affinity of 0.14 nM. The Ag binding site of basiliximab consists of all six CDR
      loops that form a large binding interface with a central shallow hydrophobic
      groove surrounded by four hydrophilic patches. The discontinuous epitope is
      composed of several segments from the D1 domain and a minor segment from the D2
      domain that overlap with most of the regions responsible for the interactions
      with IL-2. Thus, basiliximab binding can completely block the interactions of IL
      2 with IL-2R alpha and hence inhibit the activation of the IL-2 signal pathway.
      The structural results also provide important implications for the development of
      improved and new IL-2R alpha-targeted mAb drugs.

PMID- 20032295
TI  - A new strategy for the identification of novel molecules with targeted
      proresolution of inflammation properties.
AB  - As our understanding of inflammatory resolution increases, drugs that trigger
      proresolution pathways may become significant in treating chronic inflammatory
      diseases. However, anti-inflammatory drugs are traditionally tested during the
      first hours of onset (i.e., to dampen leukocyte and edema formation), and their
      ability to trigger proresolution processes has never been investigated. Moreover,
      there is no model available to screen for putative proresolving agents. In this
      study, we present a new strategy to identify therapeutics for their ability to
      switch inflammation off and restore homeostasis. Injecting 1.0 mg of zymosan i.p.
      causes transient inflammation characterized by polymorphonuclear neutrophil
      clearance and dominated by recently described resolution-phase macrophages along
      with an innate-type lymphocyte repopulation, the latter being a marker of tissue
      homeostasis. In contrast, 10 mg of zymosan elicits an aggressive response
      characterized by classically activated macrophages leading to systemic
      inflammation and impaired lymphocyte repopulation. Although this latter model
      eventually resolves, it nonetheless represents inflammation in the clinically
      relevant setting of polymorphonuclear neutrophil/classically activated macrophage
      dominance driving a cytokine storm. Treating such a reaction therapeutically with
      proresolution drugs provides quantifiable indices of resolution-
      polymorphonuclear neutrophil/macrophage clearance, macrophage phenotype switching
      (classically activated to resolution phase), and repopulation with resolution
      phase lymphocytes--cardinal signs of inflammatory resolution and homeostasis in
      the peritoneum. As an illustration, mice bearing peritonitis induced by 10 mg of
      zymosan were given ibuprofen, resolvin E1, a prostaglandin D(2) receptor 1
      agonist, dexamethasone, rolipram, or azithromycin, and their ability to trigger
      resolution and homeostasis in this new inflammatory setting was investigated. We
      present the first model for testing drugs with targeted proresolution properties
      using quantifiable parameters of inflammatory resolution and homeostasis.

PMID- 20032296
TI  - Proliferative and nonproliferative lesions of the rat and mouse respiratory
      tract.
AB  - The INHAND Project (International Harmonization of Nomenclature and Diagnostic
      Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of
      Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and
      North America (STP) to develop an internationally-accepted nomenclature for
      proliferative and non-proliferative lesions in laboratory animals. The purpose of
      this publication is to provide a standardized nomenclature for classifying
      microscopic lesions observed in the respiratory tract of laboratory rats and
      mice, with color photomicrographs illustrating examples of some lesions. The
      standardized nomenclature presented in this document is also available
      electronically on the internet (http://www.goreni.org/). Sources of material
      included histopathology databases from government, academia, and industrial
      laboratories throughout the world. Content includes spontaneous developmental and
      aging lesions as well as lesions induced by exposure to test materials. A widely
      accepted and utilized international harmonization of nomenclature for respiratory
      tract lesions in laboratory animals will decrease confusion among regulatory and
      scientific research organizations in different countries and provide a common
      language to increase and enrich international exchanges of information among
      toxicologists and pathologists.

PMID- 20032297
TI  - A comparison of acute lymphoblastic leukemia in Down syndrome and non-Down
      syndrome children: the role of trisomy 21.
AB  - Down syndrome (DS), which occurs once in every 800 births, is associated with a
      trisomy on locus 21. Among the many aberrations caused by DS, including shortened
      stature and distorted facies, are several blood dyscrasias, including childhood
      leukemias-namely, acute myeloid leukemia (AML) and acute lymphoblastic, or
      lymphocytic, leukemia (ALL). One focus of the diagnosis of ALL is to distinguish
      it from AML.The benefits of immunophenotyping extend to treatment as well. ALL is
      associated with an inherited trisomy 21 in DS children (ALL-DS) and with acquired
      trisomies, +21, 8, and 13, in non-DS children (ALL-NDS). The differences in
      treatment, outcome, and prognosis between ALL-DS and ALL-NDS can be attributed to
      the interaction of their respective trisomies with several genetic mutations,
      including one on the GATA1 growth factor transcription gene. Other mutations are
      the gene fusion at TEL/AML1, and a new mutation found, which labels the Janus
      Kinase gene or JAK2 as on oncogenic precursor, which when associated with the B
      cell precursor gene or BCP is highly leukomogenic. The treatments for the 2
      groups have been based on quality of risk, with ALL-DS children having the
      highest risk along with the poorest prognosis, but alterations in medication
      regimens have brought treatment outcomes to near equality. It is worthwhile to
      study the trisomy 21 because in the future it may provide an understanding of all
      blood dyscrasias.

PMID- 20032298
TI  - Bereaved parents' and siblings' reports of legacies created by children with
      cancer.
AB  - This qualitative study explored bereaved parents' and siblings' reports of
      legacies created by children with advanced cancer. Participants included 40
      families of children who died from cancer, with 36 mothers, 27 fathers, and 40
      siblings (ages 8-18 years). Individual interviews were completed at home
      approximately 10.68 months (SD = 3.48) after the child's death. Content analysis
      of interviews indicated that many children living with cancer did specific things
      to be remembered, such as making crafts for others, willing away belongings,
      writing letters to loved ones, and giving special gifts. Some children,
      particularly those who were very ill or died unexpectedly, did not intentionally
      do or say anything to be remembered. Legacies included bereaved individuals
      remembering children's qualities, concern for family, and beliefs about
      afterlife. Having advanced cancer appeared to motivate children to influence
      others' lives and prepare for their own deaths. Children's advice about how to
      live life inspired bereaved family members. Findings contribute to the current
      knowledge of legacy-making in children and offer implications for practice and
      future research.

PMID- 20032299
TI  - Growth velocity in pediatric bone marrow transplantation: significance of donor
      type and treatment factors.
AB  - Children who have undergone bone marrow transplantation (BMT) often have
      decreased growth. Growth is a multifactorial process, and the factors that
      influence growth after BMT are not completely understood. The authors
      hypothesized that donor type may be a factor influencing growth. Sixty-five
      children and adolescents who underwent BMT (32 related matched, 33 unrelated
      matched) were evaluated. Growth velocity (height standard deviation) was assessed
      prior to and 2 years following BMT. The results indicated that children and
      adolescents who underwent unrelated matched transplants had lower growth velocity
      (P < .059) than those with related matched transplants. Those who received the
      standard conditioning regimen that included total body irradiation (TBI) had a
      significantly lower growth velocity (P < .045) than those with chemotherapy-only
      regimens. Significant correlates of growth velocity included younger age at BMT
      and pre-BMT growth velocity. Thus, donor type, age at BMT, prior treatment, and
      BMT conditioning regimens that include TBI may all affect growth post-BMT.
      Careful monitoring of growth velocity is required for patients who have received
      an unrelated donor BMT.

PMID- 20032300
TI  - Alzheimer Abeta peptide induces chromosome mis-segregation and aneuploidy,
      including trisomy 21: requirement for tau and APP.
AB  - Both sporadic and familial Alzheimer's disease (AD) patients exhibit increased
      chromosome aneuploidy, particularly trisomy 21, in neurons and other cells.
      Significantly, trisomy 21/Down syndrome patients develop early onset AD
      pathology. We investigated the mechanism underlying mosaic chromosome aneuploidy
      in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein
      gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice
      and in transfected cells. Furthermore, adding synthetic Abeta peptide, the
      pathogenic product of APP, to cultured cells causes rapid and robust chromosome
      mis-segregation leading to aneuploid, including trisomy 21, daughters, which is
      prevented by LiCl addition or Ca(2+) chelation and is replicated in tau KO cells,
      implicating GSK-3beta, calpain, and Tau-dependent microtubule transport in the
      aneugenic activity of Abeta. Furthermore, APP KO cells are resistant to the
      aneugenic activity of Abeta, as they have been shown previously to be resistant
      to Abeta-induced tau phosphorylation and cell toxicity. These results indicate
      that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may
      thereby contribute to the pathogenesis of AD.

PMID- 20032301
TI  - Hypoxia-inducible factor-dependent regulation of platelet-activating factor
      receptor as a route for gram-positive bacterial translocation across epithelia.
AB  - Mucosal surfaces, such as the lung and intestine, are lined by a monolayer of
      epithelia that provides tissue barrier and transport function. It is recently
      appreciated that a common feature of inflammatory processes within the mucosa is
      hypoxia (so-called inflammatory hypoxia). Given the strong association between
      bacterial translocation and mucosal inflammatory disease, we hypothesized that
      intestinal epithelial hypoxia influences bacterial translocation. Initial studies
      revealed that exposure of cultured intestinal epithelia to hypoxia (pO(2), 20
      torr; 24-48 h) resulted in a increase of up to 40-fold in the translocation of
      some strains of Gram-positive bacteria, independently of epithelial barrier
      function. A screen of relevant pathway inhibitors identified a prominent role for
      the platelet-activating factor receptor (PAFr) in hypoxia-associated bacterial
      translocation, wherein pharmacologic antagonists of PAFr blocked bacterial
      translocation by as much as 80 +/- 6%. Extensions of these studies revealed that
      hypoxia prominently induces PAFr through a hypoxia-inducible factor (HIF)
      dependent mechanism. Indeed, HIF and PAFr loss of function studies (short hairpin
      RNA) revealed that apically expressed PAFr is central to the induction of
      translocation for the Gram-positive bacteria Enterococcus faecalis. Together,
      these findings reveal that some strains of Gram-positive bacteria exploit HIF
      regulated PAFr as a means for translocation through intestinal epithelial cells.

PMID- 20032302
TI  - The cell surface protein gene ecm33+ is a target of the two transcription factors
      Atf1 and Mbx1 and negatively regulates Pmk1 MAPK cell integrity signaling in
      fission yeast.
AB  - The highly conserved fission yeast Pmk1 MAPK pathway plays a key role in cell
      integrity by regulating Atf1, which belongs to the ATF/cAMP-responsive element
      binding (CREB) protein family. We identified and characterized ecm33(+), which
      encodes a glycosyl-phosphatidylinositol (GPI)-anchored cell surface protein as a
      transcriptional target of Pmk1 and Atf1. We demonstrated that the gene expression
      of Ecm33 is regulated by two transcription factors Atf1 and a MADS-box-type
      transcription factor Mbx1. We identified a putative ATF/CREB-binding site and an
      RLM1-binding site in the ecm33(+) promoter region and monitored the
      transcriptional activity of Atf1 or Mbx1 in living cells using a destabilized
      luciferase reporter gene fused to three tandem repeats of the CRE and six tandem
      repeats of the Rlm1-binding sequence, respectively. These reporter genes reflect
      the activation of the Pmk1 pathway by various stimuli, thereby enabling the real
      time monitoring of the Pmk1 cell integrity pathway. Notably, the Deltaecm33 cells
      displayed hyperactivation of the Pmk1 signaling together with hypersensitivity to
      Ca(2+) and an abnormal morphology, which were almost abolished by simultaneous
      deletion of the components of the Rho2/Pck2/Pmk1 pathway. Our results suggest
      that Ecm33 is involved in the negative feedback regulation of Pmk1 cell integrity
      signaling and is linked to cellular Ca(2+) signaling.

PMID- 20032303
TI  - Phosphoprotein enriched in astrocytes 15 kDa (PEA-15) reprograms growth factor
      signaling by inhibiting threonine phosphorylation of fibroblast receptor
      substrate 2alpha.
AB  - Changes in cellular expression of phosphoprotein enriched in astrocytes of 15 kDa
      (PEA-15) are linked to insulin resistance, tumor cell invasion, and cellular
      senescence; these changes alter the activation of the extracellular signal
      regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway. Here,
      we define the mechanism whereby increased PEA-15 expression promotes and sustains
      ERK1/2 activation. PEA-15 binding prevented ERK1/2 membrane recruitment and
      threonine phosphorylation of fibroblast receptor substrate 2alpha (FRS2alpha), a
      key link in fibroblast growth factor (FGF) receptor activation of ERK1/2. This
      reduced threonine phosphorylation led to increased FGF-induced tyrosine
      phosphorylation of FRS2alpha, thereby enhancing downstream signaling. Conversely,
      short hairpin RNA-mediated depletion of endogenous PEA-15 led to reduced
      FRS2alpha tyrosine phosphorylation. Thus, PEA-15 interrupts a negative feedback
      loop that terminates growth factor receptor signaling downstream of FRS2alpha.
      This is the dominant mechanism by which PEA-15 activates ERK1/2 because genetic
      deletion of FRS2alpha blocked the capacity of PEA-15 to activate the MAP kinase
      pathway. Thus, PEA-15 prevents ERK1/2 localization to the plasma membrane,
      thereby inhibiting ERK1/2-dependent threonine phosphorylation of FRS2alpha to
      promote activation of the ERK1/2 MAP kinase pathway.

PMID- 20032304
TI  - Vascular endothelial-cadherin stabilizes at cell-cell junctions by anchoring to
      circumferential actin bundles through alpha- and beta-catenins in cyclic AMP-Epac
      Rap1 signal-activated endothelial cells.
AB  - Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in
      endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal
      enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how
      cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell
      contacts. Forskolin induced circumferential actin bundling and accumulation of VE
      cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin
      filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC
      GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These
      effects of forskolin were mimicked by an activator for Epac but not by that for
      protein kinase A. Forskolin-induced both accumulation and stabilization of
      junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-catenin, and
      beta-catenin were dispensable for forskolin-induced circumferential actin
      bundling, indicating that homophilic VE-cadherin association is not the trigger
      of actin bundling. Requirement of alpha- and beta-catenins for forskolin-induced
      stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses
      using VEC-GFP mutants, supporting the classical model that alpha-catenin could
      potentially link the bundled actin to cadherin. Collectively, circumferential
      actin bundle formation and subsequent linkage between actin bundles and VE
      cadherin through alpha- and beta-catenins are important for the stabilization of
      VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.

PMID- 20032305
TI  - Regulation of tRNA bidirectional nuclear-cytoplasmic trafficking in Saccharomyces
      cerevisiae.
AB  - tRNAs in yeast and vertebrate cells move bidirectionally and reversibly between
      the nucleus and the cytoplasm. We investigated roles of members of the beta
      importin family in tRNA subcellular dynamics. Retrograde import of tRNA into the
      nucleus is dependent, directly or indirectly, upon Mtr10. tRNA nuclear export
      utilizes at least two members of the beta-importin family. The beta-importins
      involved in nuclear export have shared and exclusive functions. Los1 functions in
      both the tRNA primary export and the tRNA reexport processes. Msn5 is unable to
      export tRNAs in the primary round of export if the tRNAs are encoded by intron
      containing genes, and for these tRNAs Msn5 functions primarily in their reexport
      to the cytoplasm. The data support a model in which tRNA retrograde import to the
      nucleus is a constitutive process; in contrast, reexport of the imported tRNAs
      back to the cytoplasm is regulated by the availability of nutrients to cells and
      by tRNA aminoacylation in the nucleus. Finally, we implicate Tef1, the yeast
      orthologue of translation elongation factor eEF1A, in the tRNA reexport process
      and show that its subcellular distribution between the nucleus and cytoplasm is
      dependent upon Mtr10 and Msn5.

PMID- 20032306
TI  - Plasticity-related gene 5 (PRG5) induces filopodia and neurite growth and impedes
      lysophosphatidic acid- and nogo-A-mediated axonal retraction.
AB  - Members of the plasticity-related gene (PRG1-4) family are brain-specific
      integral membrane proteins and implicated in neuronal plasticity, such as
      filopodia formation and axon growth after brain lesion. Here we report on the
      cloning of a novel member of the PRG family, PRG5, with high homologies to PRG3.
      PRG5 is regulated during brain and spinal cord development and is exclusively
      allocated within the nervous system. When introduced in neurons, PRG5 is
      distributed in the plasma membrane and induces filopodia as well as axon
      elongation and growth. Conversely, siRNA mediated knockdown of PRG5 impedes axon
      growth and disturbs filopodia formation. Here we show that PRG5 induces filopodia
      growth independently of Cdc42. Moreover, axon collapse and RhoA activation
      induced by LPA and myelin-associated neurite inhibitor Nogo-A is attenuated in
      the presence of PRG5, although direct activation of the RhoA-Rho-PIP5K kinase
      pathway abolishes PRG5 -formed neurites. Thus, we describe here the
      identification of a novel member of the PRG family that induces filopodia and
      axon elongation in a Cdc42-independent manner. In addition, PRG5 impedes brain
      injury-associated growth inhibitory signals upstream of the RhoA-Rho kinase
      pathway.

PMID- 20032307
TI  - Autophosphorylation of polo-like kinase 4 and its role in centriole duplication.
AB  - Centrosome duplication occurs once every cell cycle in a strictly controlled
      manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase
      activity is essential for centriole duplication. Here, we show that PLK4
      autophosphorylation of serine S305 is a consequence of kinase activation and
      enables the active fraction to be identified in the cell. Active PLK4 is
      detectable on the replicating mother centriole in G1/S, with the proportion of
      active kinase increasing through interphase to reach a maximum in mitosis.
      Activation of PLK4 at the replicating daughter centriole is delayed until G2, but
      a level equivalent to the replicating mother centriole is achieved in M phase.
      Active PLK4 is regulated by the proteasome, because either proteasome inhibition
      or mutation of the degron motif of PLK4 results in the accumulation of S305
      phosphorylated PLK4. Autophosphorylation probably plays a role in the process of
      centriole duplication, because mimicking S305 phosphorylation enhances the
      ability of overexpressed PLK4 to induce centriole amplification. Importantly, we
      show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome
      contrary to the nonphosphorylated form. These data suggest that PLK4 activity is
      restricted to the centrosome to prevent aberrant centriole assembly and sustained
      kinase activity is required for centriole duplication.

PMID- 20032308
TI  - Interplay between ER exit code and domain conformation in CFTR misprocessing and
      rescue.
AB  - Multiple mutations in cystic fibrosis transmembrane conductance regulator (CFTR)
      impair its exit from the endoplasmic reticulum (ER). We compared two processing
      mutants: DeltaF508 and the ER exit code mutant DAA. Although both have severe
      kinetic processing defect, DAA but not DeltaF508 has substantial accumulation in
      its mature form, leading to higher level of processing at the steady state. DAA
      has much less profound conformational abnormalities. It has lower Hsp70
      association and higher post-ER stability than DeltaF508. The ER exit code is
      necessary for DeltaF508 residual export and rescue. R555K, a mutation that
      rescues DeltaF508 misprocessing, improves Sec24 association and enhances its post
      ER stability. Using in situ limited proteolysis, we demonstrated a clear change
      in trypsin sensitivity in DeltaF508 NBD1, which is reversed, together with that
      of other domains, by low temperature, R555K or both. We observed a conversion of
      the proteolytic pattern of DAA from the one resembling DeltaF508 to the one
      similar to wild-type CFTR during its maturation. Low temperature and R555K are
      additive in improving DeltaF508 conformational maturation and processing. Our
      data reveal a dual contribution of ER exit code and domain conformation to CFTR
      misprocessing and underscore the importance of conformational repair in effective
      rescue of DeltaF508.

PMID- 20032309
TI  - Posttranslational modifications of tubulin and the polarized transport of kinesin
      1 in neurons.
AB  - Polarized transport by microtubule-based motors is critical for neuronal
      development and function. Selective translocation of the Kinesin-1 motor domain
      is the earliest known marker of axonal identity, occurring before morphological
      differentiation. Thus, Kinesin-1-mediated transport may contribute to axonal
      specification. We tested whether posttranslational modifications of tubulin
      influence the ability of Kinesin-1 motors to distinguish microtubule tracks
      during neuronal development. We detected no difference in microtubule stability
      between axons and minor neurites in polarized stage 3 hippocampal neurons. In
      contrast, microtubule modifications were enriched in a subset of neurites in
      unpolarized stage 2 cells and the developing axon in polarized stage 3 cells.
      This enrichment correlated with the selective accumulation of constitutively
      active Kinesin-1 motors. Increasing tubulin acetylation, without altering the
      levels of other tubulin modifications, did not alter the selectivity of Kinesin-1
      accumulation in polarized cells. However, globally enhancing tubulin acetylation,
      detyrosination, and polyglutamylation by Taxol treatment or inhibition of
      glycogen synthase kinase 3beta decreased the selectivity of Kinesin-1
      translocation and led to the formation of multiple axons. Although microtubule
      acetylation enhances the motility of Kinesin-1, the preferential translocation of
      Kinesin-1 on axonal microtubules in polarized neuronal cells is not determined by
      acetylation alone but is probably specified by a combination of tubulin
      modifications.

PMID- 20032310
TI  - Rural-urban differences in breastfeeding initiation in the United States.
AB  - Research has noted a rural disadvantage in breastfeeding initiation; however,
      most previous research has been based on nonrepresentative samples and has been
      limited in its ability to compare racial/ethnic differences in breastfeeding
      initiation based on residential location. This research fills this gap by
      examining a nationally representative sample of births using the Early Childhood
      Longitudinal Study-Birth Cohort (ECLS-B) to explore associations between rural
      urban residence and maternal race/ethnicity on breastfeeding initiation. Results
      indicate that associations observed for rural-urban breastfeeding initiation
      differ based on maternal race/ethnicity and poverty status. These patterns likely
      reflect differences in economic resources, work environments, and social support
      among rural minority postpartum women.

PMID- 20032311
TI  - Iron concentrations in breast milk and selected maternal factors of human milk
      bank donors.
AB  - The aim of this study was to evaluate the relationship between iron concentration
      in mature breast milk and characteristics of 136 donors of a Brazilian milk bank.
      Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and
      maternal blood. Data were collected on maternal anthropometrics, obstetric,
      socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk
      and zinc and copper in blood were detected by spectrophotometry. Vitamin A in
      milk and blood was determined by high-performance liquid chromatography.
      Hemoglobin was measured by electronic counting and serum iron and ferritin by
      colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin
      were determined by nephelometry. According to multivariate linear regression
      analysis, iron in milk was positively associated with vitamin A in milk and with
      smoking but negatively associated with timing of breast milk donation (P < .001).
      These results indicate that iron concentration in milk of Brazilian donors may be
      influenced by nutritional factors and smoking.

PMID- 20032312
TI  - Beta arcades: recurring motifs in naturally occurring and disease-related amyloid
      fibrils.
AB  - Amyloid fibrils are filamentous protein aggregates that accumulate in diseases
      such as Alzheimer's or type II diabetes. The amyloid-forming protein is disease
      specific. Amyloids may also be formed in vitro from many other proteins, after
      first denaturing them. Unlike the diverse native folds of these proteins, their
      amyloids are fundamentally similar in being rigid, smooth-sided, and cross-beta
      structured, that is, with beta strands running perpendicular to the fibril axis.
      In the absence of high-resolution fibril structures, increasingly credible models
      are being derived by integrating data from a crossfire of experimental
      techniques. Most current models of disease-related amyloids invoke "beta
      arcades," columnar structures produced by in-register stacking of "beta arches."
      A beta arch is a strand-turn-strand motif in which the two beta strands interact
      via their side chains, not via the polypeptide backbone as in a conventional beta
      hairpin. Crystal structures of beta-solenoids, a class of proteins with amyloid
      like properties, offer insight into the beta-arc turns found in beta arches.
      General conformational and thermodynamic considerations suggest that complexes of
      2 or more beta arches may nucleate amyloid fibrillogenesis in vivo. The apparent
      prevalence of beta arches and their components have implications for identifying
      amyloidogenic sequences, elucidating fibril polymorphisms, predicting the
      locations and conformations of beta arcs within amyloid fibrils, and refining
      existing fibril models.

PMID- 20032313
TI  - Uncovering an IL-10-dependent NF-kappaB recruitment to the IL-1ra promoter that
      is impaired in STAT3 functionally defective patients.
AB  - The interleukin 1 receptor antagonist (IL-1ra) is an important negative regulator
      of the inflammatory response, whose genetic deficiency has been recently shown to
      cause a severe autoinflammatory syndrome in humans. In this study we
      characterized the molecular mechanisms whereby interleukin 10 (IL-10) potentiates
      IL-1ra transcription in LPS-stimulated monocytes and neutrophils. Using chromatin
      immunoprecipitation, we show that although NF-kappaBp65 and NF-kappaBp50 proteins
      accumulate into the nuclei and bind to the IkappaB alpha promoter during LPS
      stimulation, they are not recruited to the kappaB sites of the IL-1ra promoter.
      However, in response to LPS plus IL-10, which were found to induce chromatin
      acetylation, recruitment of both NF-kappaBp65 and NF-kappaBp50 to the IL-1ra
      promoter efficiently occurs in a STAT3-dependent manner. Accordingly, in
      neutrophils from hyper-IgE syndrome patients, who carry a nonfunctional STAT3, IL
      10 failed to promote NF-kappaBp65 recruitment to the IL-1ra promoter and
      consequently to potentiate LPS-induced IL-1ra transcription. Altogether our
      findings uncover a novel mechanism whereby IL-10-activated STAT3 modulates IL-1ra
      transcription in LPS-treated phagocytes by making IL-1ra promoter accessible to
      readily available nuclear NF-kappaB.

PMID- 20032315
TI  - Medicine's ethical responsibility for health care reform--the Top Five list.

PMID- 20032314
TI  - High glucose inhibits glucose-6-phosphate dehydrogenase, leading to increased
      oxidative stress and beta-cell apoptosis.
AB  - Patients with type 2 diabetes lose beta cells, but the underlying mechanisms are
      incompletely understood. Glucose-6-phosphate dehydrogenase (G6PD) is the
      principal source of the major intracellular reductant, NADPH, which is required
      by many enzymes, including enzymes of the antioxidant pathway. Previous work from
      our laboratory has shown that high glucose impairs G6PD activity in endothelial
      and kidney cells, which leads to decreased cell survival. Pancreatic beta cells
      are highly sensitive to increased ROS. This study aimed to determine whether G6PD
      and NADPH play central roles in beta-cell survival. Human and mouse islets, MIN6
      cell line, and G6PD deficient mice were studied. High glucose inhibited G6PD
      expression and activity. Inhibition of G6PD with siRNA led to increased ROS and
      apoptosis, decreased proliferation, and impaired insulin secretion. High glucose
      decreased insulin secretion, which was improved by overexpressing G6PD. G6PD
      deficient mice had smaller islets and impaired glucose tolerance compared with
      control mice, which suggests that G6PD deficiency per se leads to beta-cell
      dysfunction and death. G6PD plays an important role in beta-cell function and
      survival. High-glucose-mediated decrease in G6PD activity may provide a
      mechanistic explanation for the gradual loss of beta cells in patients with
      diabetes.

PMID- 20032316
TI  - American values and health care reform.

PMID- 20032317
TI  - Intravenous zanamivir for oseltamivir-resistant 2009 H1N1 influenza.

PMID- 20032318
TI  - Variants of DENND1B associated with asthma in children.
AB  - BACKGROUND: Asthma is a complex disease that has genetic and environmental
      causes. The genetic factors associated with susceptibility to asthma remain
      largely unknown. METHODS: We carried out a genomewide association study involving
      children with asthma. The sample included 793 North American children of European
      ancestry with persistent asthma who required daily inhaled glucocorticoid therapy
      and 1988 matched controls (the discovery set). We also tested for genomewide
      association in an independent cohort of 917 persons of European ancestry who had
      asthma and 1546 matched controls (the replication set). Finally, we tested for an
      association between 20 single-nucleotide polymorphisms (SNPs) at chromosome 1q31
      and asthma in 1667 North American children of African ancestry who had asthma and
      2045 ancestrally matched controls. RESULTS: In our meta-analysis of all samples
      from persons of European ancestry, we observed an association, with genomewide
      significance, between asthma and SNPs at the previously reported locus on 17q21
      and an additional eight SNPs at a novel locus on 1q31. The SNP most strongly
      associated with asthma was rs2786098 (P=8.55x10(-9)). We observed replication of
      the association of asthma with SNP rs2786098 in the independent series of persons
      of European ancestry (combined P=9.3x10(-11)). The alternative allele of each of
      the eight SNPs on chromosome 1q31 was strongly associated with asthma in the
      children of African ancestry (P=1.6x10(-13) for the comparison across all
      samples). The 1q31 locus contains the 1q31 locus contains DENND1B, a gene
      expressed by natural killer cells and dendritic cells. DENND1B protein is
      predicted to interact with the tumor necrosis factor alpha receptor [corrected].
      CONCLUSIONS: We have identified a locus containing DENND1B on chromosome 1q31.3
      that is associated with susceptibility to asthma.

PMID- 20032319
TI  - Severe 2009 H1N1 influenza in pregnant and postpartum women in California.
AB  - BACKGROUND: Like previous epidemic and pandemic diseases, 2009 pandemic influenza
      A (H1N1) may pose an increased risk of severe illness in pregnant women. METHODS:
      Statewide surveillance for patients who were hospitalized with or died from 2009
      H1N1 influenza was initiated by the California Department of Public Health. We
      reviewed demographic and clinical data reported from April 23 through August 11,
      2009, for all H1N1-infected, reproductive-age women who were hospitalized or died
      -nonpregnant women, pregnant women, and postpartum women (those who had delivered
      < or = 2 weeks previously). RESULTS: Data were reported for 94 pregnant women, 8
      postpartum women, and 137 nonpregnant women of reproductive age who were
      hospitalized with 2009 H1N1 influenza. Rapid antigen tests were falsely negative
      in 38% of the patients tested (58 of 153). Most pregnant patients (89 of 94
      [95%]) were in the second or third trimester, and approximately one third (32 of
      93 [34%]) had established risk factors for complications from influenza other
      than pregnancy. As compared with early antiviral treatment (administered < or = 2
      days after symptom onset) in pregnant women, later treatment was associated with
      admission to an intensive care unit (ICU) or death (relative risk, 4.3). In all,
      18 pregnant women and 4 postpartum women (total, 22 of 102 [22%]) required
      intensive care, and 8 (8%) died. Six deliveries occurred in the ICU, including
      four emergency cesarean deliveries. The 2009 H1N1 influenza-specific maternal
      mortality ratio (the number of maternal deaths per 100,000 live births) was 4.3.
      CONCLUSIONS: 2009 H1N1 influenza can cause severe illness and death in pregnant
      and postpartum women; regardless of the results of rapid antigen testing, prompt
      evaluation and antiviral treatment of influenza-like illness should be considered
      in such women. The high cause-specific maternal mortality rate suggests that 2009
      H1N1 influenza may increase the 2009 maternal mortality ratio in the United
      States.

PMID- 20032321
TI  - Videos in clinical medicine. Endometrial biopsy.

PMID- 20032320
TI  - Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in
      Argentina.
AB  - BACKGROUND: While the Northern Hemisphere experiences the effects of the 2009
      pandemic influenza A (H1N1) virus, data from the recent influenza season in the
      Southern Hemisphere can provide important information on the burden of disease in
      children. METHODS: We conducted a retrospective case series involving children
      with acute infection of the lower respiratory tract or fever in whom 2009 H1N1
      influenza was diagnosed on reverse-transcriptase polymerase-chain-reaction assay
      and who were admitted to one of six pediatric hospitals serving a catchment area
      of 1.2 million children. We compared rates of admission and death with those
      among age-matched children who had been infected with seasonal influenza strains
      in previous years. RESULTS: Between May and July 2009, a total of 251 children
      were hospitalized with 2009 H1N1 influenza. Rates of hospitalization were double
      those for seasonal influenza in 2008. Of the children who were hospitalized, 47
      (19%) were admitted to an intensive care unit, 42 (17%) required mechanical
      ventilation, and 13 (5%) died. The overall rate of death was 1.1 per 100,000
      children, as compared with 0.1 per 100,000 children for seasonal influenza in
      2007. (No pediatric deaths associated with seasonal influenza were reported in
      2008.) Most deaths were caused by refractory hypoxemia in infants under 1 year of
      age (death rate, 7.6 per 100,000). CONCLUSIONS: Pandemic 2009 H1N1 influenza was
      associated with pediatric death rates that were 10 times the rates for seasonal
      influenza in previous years.

PMID- 20032322
TI  - Images in clinical medicine. Coughing and masks.

PMID- 20032324
TI  - Clinical practice. Barrett's esophagus.

PMID- 20032325
TI  - Images in clinical medicine. Intrathoracic rib.

PMID- 20032326
TI  - Case records of the Massachusetts General Hospital. Case 40-2009. A 29-year-old
      man with Fever and respiratory failure.

PMID- 20032327
TI  - Lp(a) lipoprotein redux--from curious molecule to causal risk factor.

PMID- 20032328
TI  - Sensitive cardiac troponin assays.

PMID- 20032329
TI  - Injectable collagenase clostridium histolyticum for Dupuytren's contracture.

PMID- 20032323
TI  - Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
AB  - BACKGROUND: An increased level of Lp(a) lipoprotein has been identified as a risk
      factor for coronary artery disease that is highly heritable. The genetic
      determinants of the Lp(a) lipoprotein level and their relevance for the risk of
      coronary disease are incompletely understood. METHODS: We used a novel gene chip
      containing 48,742 single-nucleotide polymorphisms (SNPs) in 2100 candidate genes
      to test for associations in 3145 case subjects with coronary disease and 3352
      control subjects. Replication was tested in three independent populations
      involving 4846 additional case subjects with coronary disease and 4594 control
      subjects. RESULTS: Three chromosomal regions (6q26-27, 9p21, and 1p13) were
      strongly associated with the risk of coronary disease. The LPA locus on 6q26-27
      encoding Lp(a) lipoprotein had the strongest association. We identified a common
      variant (rs10455872) at the LPA locus with an odds ratio for coronary disease of
      1.70 (95% confidence interval [CI], 1.49 to 1.95) and another independent variant
      (rs3798220) with an odds ratio of 1.92 (95% CI, 1.48 to 2.49). Both variants were
      strongly associated with an increased level of Lp(a) lipoprotein, a reduced copy
      number in LPA (which determines the number of kringle IV-type 2 repeats), and a
      small Lp(a) lipoprotein size. Replication studies confirmed the effects of both
      variants on the Lp(a) lipoprotein level and the risk of coronary disease. A meta
      analysis showed that with a genotype score involving both LPA SNPs, the odds
      ratios for coronary disease were 1.51 (95% CI, 1.38 to 1.66) for one variant and
      2.57 (95% CI, 1.80 to 3.67) for two or more variants. After adjustment for the
      Lp(a) lipoprotein level, the association between the LPA genotype score and the
      risk of coronary disease was abolished. CONCLUSIONS: We identified two LPA
      variants that were strongly associated with both an increased level of Lp(a)
      lipoprotein and an increased risk of coronary disease. Our findings provide
      support for a causal role of Lp(a) lipoprotein in coronary disease.

PMID- 20032330
TI  - Anthracycline dose intensification in acute myeloid leukemia.

PMID- 20032331
TI  - Sudden infant death syndrome.

PMID- 20032332
TI  - Bacterial pathogens and death during the 1918 influenza pandemic.

PMID- 20032333
TI  - Holiday spikes in pneumococcal disease among older adults.

PMID- 20032374
TI  - Cytogenetic effects of exposure to 2.3 GHz radiofrequency radiation on human
      lymphocytes in vitro.
AB  - BACKGROUND: No previous in vitro studies have tested radio frequency radiation
      for at least one full cell cycle in culture. The aim was to test if exposure used
      in mobile phones and wireless network technologies would induce DNA damage in
      cultured human lymphocytes with and without a known clastogen. MATERIALS AND
      METHODS: Lymphocytes from six donors were exposed to 2.3 GHz, 10 W/m(2)
      continuous waves, or 2.3 GHz, 10 W/m(2) pulsed waves (200 Hz pulse frequency, 50%
      duty cycle). Mitomycin C was added to half of the cultures. DNA synthesis and
      repair were inhibited in one experiment. RESULTS: No statistically significant
      differences were observed between control and exposed cultures. A weak trend for
      more chromosomal damage with the interaction of pulsed fields with mitomycin C
      compared to a constant field was observed. CONCLUSION: Exposure during the whole
      cell cycle in inhibited cultures did not resulted in significant differences in
      chromosomal aberrations as compared to controls.

PMID- 20032373
TI  - Preferential expression of the secreted and membrane forms of tumor endothelial
      marker 7 transcripts in osteosarcoma.
AB  - BACKGROUND: High expression of tumor endothelial marker 7 (TEM7) is correlated
      with osteogenic sarcoma (OS) metastasis and poor survival of patients. The TEM7
      gene produces four alternatively spliced transcripts with distinct functional
      domains; the expression pattern of these transcripts in OS is unknown. MATERIALS
      AND METHODS: mRNA expression was assessed in 5 OS cell lines, 7 normal bone, and
      9 OS tumor specimens by reverse transcriptase polymerase chain reaction. RESULTS:
      All OS cell lines, 6/9 tumors but none of the bone specimens expressed mRNA of
      TEM7 secreted forms 1 and 2. A total of 3/5 OS cell lines, 8/9 of tumors and 4/7
      of bone specimens expressed mRNA of the TEM7 intracellular form. One out of 5
      cell lines, 2/7 tumors and none of the bone specimens expressed mRNA of the TEM7
      membrane form. The secreted forms had 20-fold higher expression in metastatic
      (LM7) compared to non-metastatic (SAOS-2) cells. CONCLUSION: The mRNA of secreted
      and the membrane forms of TEM7 are preferentially expressed in OS.

PMID- 20032375
TI  - Establishment and characterization of a human gastrointestinal stromal tumour
      (GIST) xenograft in athymic nude mice.
AB  - BACKGROUND: The majority of gastrointestinal stromal tumours (GISTs) contain
      oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or
      platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK)
      mutations and are initially, but only temporarily sensitive to TK inhibitors. The
      aim of this study was to establish and characterize a human GIST xenograft that
      could be used for evaluating various molecularly targeted therapies. MATERIALS
      AND METHODS: GIST tissue from four patients was implanted under the skin of
      athymic nude mice. In one case a tumour line was established. RESULTS: The
      xenograft showed characteristic GIST morphology and exhibited the same mutation
      profile as that of the patient. CONCLUSION: A human GIST xenograft with mutation
      in KIT exons 11 and 17 has been established and maintained in nude mice for 3
      years (13 passages). This model will enable further studies on mechanisms of
      resistance, combination therapies and allow testing of novel targeted therapies.

PMID- 20032376
TI  - Mutation analysis of hypoxia-inducible factors HIF1A and HIF2A in renal cell
      carcinoma.
AB  - BACKGROUND: Inactivation of the Von Hippel-Lindau (VHL) tumour suppressor gene
      leading to overexpression of hypoxia-inducible transcription factors (HIF)-1alpha
      and -2alpha is a critical event in the pathogenesis of most clear cell renal cell
      carcinomas (RCC). HIF-1alpha and HIF-2alpha share significant homology and
      regulate overlapping repertoires of hypoxia-inducible target genes but may have
      differing effects on RCC cell growth. Loss of HIF-1alpha expression has been
      described in RCC cell lines and primary tumours. Whether mutations in the alpha
      subunits of HIF-1alpha and HIF-2alpha contribute to renal tumourigenesis was
      investigated here. MATERIALS AND METHODS: Mutation analysis of the complete
      coding sequence of HIF-1alpha and HIF-2alpha was carried out in primary RCC
      (n=40). RESULTS: The analysis revealed a somatic HIF1A missense substitution,
      p.Val116Glu, in a single RCC. Functional studies demonstrated that p.Val116Glu
      impaired HIF-1alpha transcriptional activity. Genotyping of HIF1A variants
      p.Pro582Ser and p.Ala588Thr demonstrated no significant differences between RCC
      patients and controls. CONCLUSION: The detection of a loss-of-function HIF1A
      mutation in a primary RCC is consistent with HIF-1 and HIF-2 having different
      roles in renal tumourigenesis, However, somatic mutations of HIF1A are not
      frequently implicated in the pathogenesis of RCC.

PMID- 20032377
TI  - Expression of the CD117, COX-2 and HSP90 antigens and cell proliferation in fine
      needle-aspirated cells from metastatic melanomas.
AB  - BACKGROUND: Blocking therapies aimed at COX-2, HSP90 and CD117 have been
      described recently. The objective of the study was to analyze expression of these
      antigens and the proliferation rate in metastatic melanomas. MATERIALS AND
      METHODS: Fine-needle aspirates from 30 patients were analyzed. Immunocytochemical
      methods were applied to assess COX-2, HSP-90 and CD117. Cell proliferation was
      analysed using expression of Ki-67. Findings were compared with histopathological
      parameters. RESULTS: All cases expressed COX-2 and HSP90. CD117 was expressed in
      46% of cases. The proliferation index ranged between 7% and 54%. No correlation
      was found between histological properties of the primary tumours and expression
      of CD117, COX-2 and HSP90 in their metastases. An inverse correlation was found
      between HSP90 and MIB-1 index. CONCLUSION: A large proportion of metastatic
      melanomas expressed COX-2 and HSP90. This may have a clinical implication for
      blocking therapy of the corresponding molecules. Expression of CD117 antigen was
      observed in only 5/30 melanoma cases. We hypothesize that such melanomas may
      benefit from targeted therapy with kinase inhibitors.

PMID- 20032378
TI  - Retinol-induced intestinal tumorigenesis in Min/+ mice and importance of vitamin
      D status.
AB  - The effects of life-long dietary exposure, starting in utero, to high retinol,
      low vitamin D, or high retinol in combination with low vitamin D on intestinal
      tumorigenesis in Min/+ mice were investigated. In males, high retinol alone
      significantly increased the number (2.6-fold) and size (1.3-fold) of small
      intestinal tumours; in females no significant increase in tumour number or size
      was seen. In both genders, low vitamin D intake alone did not affect intestinal
      tumorigenesis. In males, intake of the combined high retinol/low vitamin D diet
      did not further increase the effects caused by high retinol alone. In females,
      however, the high retinol/low vitamin D-induced increase in tumour number (3.1
      fold) and tumour size (1.5-fold) exceeded that of high retinol alone. In
      conclusion, a high dietary intake of retinol stimulated intestinal tumorigenesis
      in Min/+ mice. Furthermore, the results indicate a combined effect of high
      retinol and low vitamin D on tumorigenesis in females.

PMID- 20032379
TI  - Apoptotic signalling in HeLa Hep2 cells following 5 Gy of cobalt-60 gamma
      radiation.
AB  - BACKGROUND: The apoptotic signalling pathways involved in the delayed type of
      apoptosis occurring in HeLa Hep2 cells following radiation were investigated.
      MATERIALS AND METHODS: HeLa Hep2 cells were exposed to 5 Gy of cobalt-60
      radiation. The activation of caspase-2, caspase-8, caspase-9 and effector caspase
      3 was investigated by caspase assay plates and Western blots. Cleavage of poly
      (ADP-ribose) polymerase (PARP) was analysed on Western blots. HeLa Hep2 cells
      were irradiated with or without preincubation with inhibitors of protein
      synthesis (cycloheximide, CHX) and caspases, followed by TUNEL staining and
      caspase assay plate evaluation. RESULTS: Initiator caspases-2, -8, -9, and
      effector caspase-3, were found to be activated and PARP cleaved following
      irradiation. CHX completely inhibited the caspase activation and the associated
      apoptosis. Pretreatment with caspase-2 inhibitor indicated that caspase-2 was
      involved in the execution of the apoptosis. CONCLUSION: Activation of the
      apoptotic signalling pathways following irradiation of HeLa Hep2 cells includes
      components from the intrinsic as well as the extrinsic pathways and seems to
      require de novo protein synthesis.

PMID- 20032380
TI  - Activation of human monocyte-derived dendritic cells in vitro by Thymax, a gross
      thymic extract.
AB  - BACKGROUND: We have recently demonstrated that Thymax, a gross thymic extract,
      induces an apoptotic effect against human breast cancer cells. In this study, the
      ability of Thymax to activate human dendritic cells (DCs) and the DC-directed T
      cell response was examined in an in vitro culture model of peripheral blood
      mononuclear cells. MATERIALS AND METHODS: The level of costimulatory molecules
      (CD40, CD80, CD83, CD86) and T-cell proliferation were analyzed by flow
      cytometry. Cytokine secretion was measured by ELISA. RESULTS: Thymax activated
      DCs to secrete interleukin (IL)-12p40 and IL-6 cytokines and inhibited IL-10
      production. Additionally, Thymax caused the up-regulation of CD80 and CD86 in
      DCs, leading to an increase in CD4(+) T-cells, which subsequently induced
      secretion of interferon-gamma (IFN-gamma). CONCLUSION: Taken together, the data
      showed that Thymax activated DCs and, consequently, Th1 cells. Thus, Thymax is an
      immune-activating compound that needs to be evaluated extensively for its
      possible therapeutic properties.

PMID- 20032381
TI  - ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane
      resistant tumor models.
AB  - AIM: Profiling the efficacy and pharmacodynamic activity of the kinesin spindle
      protein (KSP) inhibitor ARRY-520 will aid the identification of responsive tumor
      types and pharmacodynamic profiles that correlate with activity. MATERIALS AND
      METHODS: In vivo activity was evaluated in a diverse panel of 16 different tumor
      xenograft models. Pharmacodynamic activity was evaluated in selected models.
      RESULTS: ARRY-520 had low nanomolar antiproliferative activity in tumor cell
      lines. Monopolar spindles were formed at active potencies. Partial or complete
      responses were observed in 13/16 xenograft models. Hematological tumors were
      particularly sensitive, with a 100% complete response rate in some models.
      Maintenance of mitotic block for a sufficient length of time for cells to lose
      survival signals and progress to apoptosis was a key component of the mechanism
      of activity. ARRY-520 was also active in several taxane resistant models.
      CONCLUSION: The data provide a rationale for clinical evaluation of the activity
      of ARRY-520 in hematological carcinomas and taxane-resistant tumors.

PMID- 20032383
TI  - An immunocompetent murine model of metastatic mammary cancer accessible to
      bioluminescence imaging.
AB  - BACKGROUND: Many areas of research, including gene and pharmacological
      therapeutics, would benefit from longitudinal in vivo monitoring methodologies.
      To investigate the feasibility of one such methodology, we developed a murine
      mammary cancer model amenable to sequential bioluminescent imaging of tumor
      growth and metastasis in living animals. MATERIALS AND METHODS: Metastatic mouse
      mammary carcinoma BJMC3879 cells were transfected to stably express firefly
      luciferase and inoculated into immunocompetent female BALB/c mice. RESULTS:
      Sequential analysis using bioluminescent imaging showed increasing photon counts
      correlated to expanding mammary tumor volumes; in addition, strong signals from
      axillary, mandibular, femoral, thoracic and abdominal regions in mice were
      histopathologically determined to be due to metastases, the majority of which
      occurred in lymph nodes and lungs. CONCLUSION: The bioluminescent mouse mammary
      cancer model we established provides a method for quantifiable longitudinal in
      vivo imaging that can be used in gene and pharmacological therapy applications.

PMID- 20032382
TI  - Aneuploidy is associated with TP53 expression but not with BRCA1 or TERT
      expression in sporadic colorectal cancer.
AB  - BACKGROUND: Defective expression of genes involved in mitotic chromosome
      segregation (e.g. AURKA, BUB1B), DNA damage response (e.g. TP53, BRCA1), and
      telomere function (e.g. TERT) may play a role in the development of tumor
      aneuploidy. MATERIALS AND METHODS: The levels of TP53, BRCA1 and TERT were
      assessed in 55 sporadic colorectal tumors and 37 normal mucosas using tissue
      microarrays and immunohistochemical detection, and their associations with DNA
      aneuploidy, levels of mitotic spindle proteins AURKA, AURKB, MAD2L1 and BUB1B and
      clinicopathological parameters were investigated. RESULTS: DNA aneuploidy was
      associated only with TP53 alterations. BRCA1 expression in tumors was
      significantly correlated with individual mitotic spindle protein expressions, and
      TERT and MAD2L1 expressions were moderately correlated in the tumor group,
      suggesting a putative role for TERT in MAD2L1 regulation. CONCLUSION: Loss of
      TP53 function appears to be involved in the development of aneuploidy, but not in
      the deregulation of mitotic spindle protein function.

PMID- 20032384
TI  - Changes in UNC5C gene methylation during human gastric carcinogenesis.
AB  - BACKGROUND: UNC5C, 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, aberrant methylation of the
      UNC5C gene was found in 34 out of 49 (69%) primary colon carcinomas. MATERIALS
      AND METHODS: The methylation status of the UNC5C 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,
      and the correlation between the methylation status and the clinicopathological
      findings was evaluated. RESULTS: Aberrant methylation of the UNC5C gene was
      detected in 9 out of the 36 (25%) primary gastric carcinomas. A significant
      difference was observed in regard to the TNM stage (p=0.0455). CONCLUSION: UNC5C
      methylation was observed in the course of gastric carcinogenesis and disappeared
      in highly advanced gastric carcinomas.

PMID- 20032385
TI  - Voluntary wheel running in rats receiving doxorubicin: effects on running
      activity and cardiac myosin heavy chain.
AB  - BACKGROUND: The clinical use of the highly effective chemotherapeutic agent
      doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. This
      cardiotoxicity is associated with a cardiac myosin heavy chain (MHC) isoform
      shift from the alpha isoform to the beta isoform. Exercise prior to DOX treatment
      has been shown to attenuate the MHC shift associated with DOX, but little is
      known about the cardioprotective nature of exercise during DOX treatment.
      MATERIALS AND METHODS: DOX-treated rats were assigned to normal cage activity
      (sedentary, SED+DOX) or 24-hour voluntary wheel running access (WR+DOX). All
      animals received weekly 2.5 mg/kg DOX injections for 6 weeks (15 mg/kg
      cumulative) and hearts were subsequently excised for determination of MHC isoform
      expression using sodium dodecyl sulfate polyacrylamide gel electrophoresis.
      RESULTS: At baseline, WR+DOX rats on average ran 62+/-4 km, and at week 6 ran
      30+/-5 km, which was significantly lower than baseline (p<0.05). SED+DOX hearts
      expressed 57+/-7% of MHC as the alpha-MHC isoform and 43+/-7% as the beta-MHC
      isoform. WR+DOX hearts expressed 76+/-4% as the alpha-MHC and 24+/-4% as the beta
      MHC isoform, which was significantly different from that of SED+DOX (p<0.05).
      CONCLUSION: DOX treatment significantly reduced wheel running activity, but this
      reduced running distance deemed to be cardioprotective as hearts from WR+DOX rats
      contained significantly greater levels of the favorable alpha-MHC isoform than
      SED+DOX.

PMID- 20032386
TI  - Imexon augments sensitivity of human lymphoma cells to ionizing radiation: in
      vitro experimental study.
AB  - BACKGROUND: Imexon is an aziridine-containing small pro-oxidant molecule with
      promising antitumor activity in myeloma, lymphoma and lung and pancreatic cancer.
      Imexon is already in clinical trials in patients with advanced solid tumors. The
      present study examined the effects of imexon on H9 and Raji lymphoma cell lines
      in vitro when given in combination with ionizing radiation. MATERIALS AND
      METHODS: H9 and Raji lymphoma cells were grown in culture and exposed to imexon,
      radiation, or both. Cells were assessed for cell viability, glutathione content,
      induction of apoptosis, cell cycle distribution and also subject to Western blot
      analysis. RESULTS: Imexon inhibited cell proliferation in a dose-dependent
      manner. Imexon, given for 48 h prior to irradiation at a clinically achievable
      dose of 40 muM, potently enhanced the cell radiosensitivity. Imexon enhanced
      radiation-induced apoptosis and accumulated cells in G2/M phase of the cell
      cycle. Imexon induced caspase-3 activation and PARP cleavage. Alterations in
      glutathione levels were not observed at 40 microM of imexon. CONCLUSION: In
      conclusion, imexon efficiently augmented lymphoma cell radiosensitivity
      independently of glutathione and the underlying mechanisms include induction of
      apoptosis and cell cycle redistribution.

PMID- 20032387
TI  - Differing expression of metalloprotease and of adhesion molecules in signet-ring
      cell and intestinal colorectal carcinoma.
AB  - BACKGROUND: Pure signet-ring cell colorectal carcinoma (SRCC) is an infrequent
      and highly malignant histological variant of colorectal cancer (CRC), while it is
      present as a histological component in colorectal carcinomas more frequently.
      MATERIALS AND METHODS: The aim of this work was to widen the knowledge of the
      biological factors involved in the pathogenesis and aggressiveness of SRCC by the
      identification and evaluation of possible molecular abnormalities. By means of
      immunohistochemistry the expression of the proteolytic degradation enzyme matrix
      metalloprotease (MMP)-1, that is a collagenase specifically degrading collagens
      I, II, III and of the adhesion proteins E-cadherin, beta-catenin and fibronectin
      which are usually involved in the carcinogenesis of conventional colorectal
      tumours was investigated. RESULTS: SRCCs showed a significantly greater MMP-1
      expression compared to the ordinary intestinal colorectal cancer (ICRC) and a
      significantly reduced E-cadherin, beta-catenin and fibronectin expression.
      CONCLUSION: The biological aggressiveness and strong metastatic behaviour of SRCC
      could be due to high MMP-1 and low expression of the adhesion molecules.

PMID- 20032388
TI  - p38 inhibitor intensified cell death in antimycin A-treated As4.1 juxtaglomerular
      cells via the enhancement of GSH depletion.
AB  - Antimycin A (AMA) inhibits succinate oxidase, NADH oxidase and mitochondrial
      electron transport chain between cytochrome b and c. Here, we investigated the
      effects of AMA and/or mitogen-activated protein kinase (MAPK) inhibitors on As4.1
      juxtaglomerular cells in relation to cell growth, cell death, reactive oxygen
      species (ROS) and glutathione (GSH) levels. Treatment with 50 nM AMA inhibited
      the growth of As4.1 cells at 48 hours and induced apoptosis, which was
      accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)). AMA
      increased ROS levels including that of intracellular O(2)(*-). AMA also induced
      GSH depletion. MEK inhibitor did not affect cell growth, cell death, DeltaPsi(m)
      loss, ROS level or GSH depletion in AMA-treated As4.1 cells. c-Jun N-terminal
      kinase (JNK) inhibitor also did not influence cell growth, cell death, ROS level
      and GSH depletion but did slightly increase DeltaPsi(m) loss. Treatment with p38
      inhibitor magnified cell growth inhibition by AMA and increased cell death,
      DeltaPsi(m) loss and GSH depletion in AMA-treated As4.1 cells. Conclusively, p38
      inhibitor intensified cell death in AMA-treated As4.1 cells. The changes of GSH
      content rather than ROS level by AMA and/or MAPK inhibitors were more closely
      related to the growth and death of As4.1 cells.

PMID- 20032389
TI  - Effects of carbon-ion radiotherapy combined with a novel histone deacetylase
      inhibitor, cyclic hydroxamic-acid-containing peptide 31 in human esophageal
      squamous cell carcinoma.
AB  - BACKGROUND: Carbon-ion radiotherapy has several potential advantages over X-rays.
      This therapy has been applied for various solid tumors including esophageal
      squamous cell carcinoma (SCC). However, some patients have shown resistance to
      this treatment. A new effective combined treatment strategy is required for
      improving the therapeutic effects. Histone deacetylase inhibitors (HDACIs) are
      new therapeutic candidates for cancer treatment. Several studies have evaluated
      the combination of X-rays and HDACIs, but, to date, no study has evaluated carbon
      ion radiotherapy combined with HDACIs. MATERIALS AND METHODS: Radio-sensitization
      to carbon-ion radiotherapy when combined with a novel HDACI cyclic hydroxamic
      acid-containing peptide 31(CHAP31) was assessed in human esophageal SCC both in
      vitro and in vivo. Changes of expression of genes related to DNA repair, by
      CHAP31 were assessed by quantitative real-time reverse transcriptional PCR
      analysis. RESULTS: CHAP31 induced sensitization to carbon-ion radiotherapy in
      vitro and tumor growth was significantly suppressed by the combination of carbon
      ion radiotherapy with CHAP31 in comparison to either agent alone in in vivo
      experiments. CHAP31 inhibited the expression of genes related to DNA repair.
      CONCLUSION: CHAP31 sensitizes SCC cells to carbon-ion radiotherapy and this
      combinatory treatment may be a potentially useful therapeutic strategy for
      esophageal SCC.

PMID- 20032391
TI  - Prognostic impact of protein overexpression of the proto-oncogene PIM-1 in
      gastric cancer.
AB  - BACKGROUND: PIM kinases are mediators of cytokine signalling pathways in
      hematopoietic cells and contribute to the progression of certain types of
      leukemia and solid tumor. Here the prognostic impact of proto-oncogene PIM-1 was
      analyzed in gastric carcinoma. PATIENTS AND METHODS: Cancer tissues of 117
      patients with potentially curative (R0) resections for gastric cancer were
      immunohistochemically stained for PIM-1. RESULTS: Cytoplasmic immunoreactivity
      for PIM-1 in tumor (46%) was higher (p=0.003) compared to that in gastric glands
      (16%) and foveolae (1%). PIM-1 immunoreactivity in gastric carcinoma correlated
      with tumor grading (p<0.05) and Lauren category (p<0.02). Overexpression of PIM-1
      in gastric glands (p<0.001) was associated with formation of lymph node
      metastases (p=0.035) and survival (p=0.04). Multivariate analysis of PIM-1
      expression in gastric glands confirmed its association with prognosis.
      CONCLUSION: Up-regulation of PIM-1 oncogene might be a tumor marker for gastric
      cancer. The correlation of PIM-1 overexpression in gastric glands with formation
      of lymph node metastases and survival proposes a prognostic role in gastric
      cancer.

PMID- 20032390
TI  - PTEN loss induces epithelial--mesenchymal transition in human colon cancer cells.
AB  - BACKGROUND: The epithelial-mesenchymal transition is a critical early event in
      the invasion and metastasis of many types of cancer, including colorectal cancer
      (CRC). Chronic inflammation is an inducer of several cancer types and
      inflammatory cytokines have been implicated in tumor invasion. MATERIALS AND
      METHODS: Human colon cancer cell lines HCT116 and SW480 were transfected with
      phosphatase and tensin homolog deleted on chromosome 10 (PTEN) siRNA or non
      targeting control (NTC). Invasiveness was measured using a modified Boyden
      chamber assay and migration was assessed using a scratch assay. RESULTS: PTEN
      knockdown increased the invasion and migration of CRC cells and the addition of
      medium containing tumor necrosis factor-alpha (TNF-alpha) further enhanced the
      migration and invasion. PTEN knockdown resulted in nuclear beta-catenin
      accumulation and increased expression of downstream proteins c-Myc and cyclin D1.
      CONCLUSION: Our study supports the findings of clinical studies identifying an
      association of PTEN loss with late stage cancer. Cellular factors secreted from
      the surrounding tumor milieu likely act in concert with genetic changes in the
      tumor cells and contribute to enhanced tumor invasion.

PMID- 20032392
TI  - Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated
      apoptosis via down-regulation of AKT and activation of caspase-3.
AB  - Sanguinarine is a benzophenanthridine alkaloid, derived from the root of
      Sanguinaria canadensis and other poppy Fumaria species, which is known to have
      antimicrobial, antiinflammatory and antioxidant properties. Tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer
      cells but spare most normal cells. However, its effects are limited in some types
      of cancer cells, including AGS human gastric adenocarcinoma cells. In the present
      study, we showed that treatment with TRAIL in combination with subtoxic
      concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in AGS cells.
      Combined treatment with sanguinarine and TRAIL effectively induced Bid cleavage
      and loss of mitochondrial membrane potential, leading to the activation of
      caspases, and cleavage of poly(ADP-ribose) polymerase and beta-catenin. The
      cytotoxic effects of the combined treatment were significantly inhibited by z
      DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase
      3 in the observed cytotoxic effect. In addition, the levels of Akt protein were
      markedly reduced in cells co-treated with sanguinarine and TRAIL. Apoptosis
      induced by the combined treatment was markedly increased by the
      phosphatidylinositol-3'-kinase inhibitor, LY294002 (Akt-upstream inhibitor),
      through the mitochondrial amplification step and caspase activation, suggesting
      that interactions of the synergistic effect were at least partially mediated
      through the Akt-dependent pathway.

PMID- 20032393
TI  - Multidrug resistance modulation and apoptosis induction of cancer cells by
      terpenic compounds isolated from Euphorbia species.
AB  - BACKGROUND: One of the most promising strategies to overcome multidrug resistance
      (MDR) is to use compounds that can modulate P-glycoprotein and restore the
      cytotoxicity of anticancer drugs. Furthermore, the search for compounds that
      regulate and overcome apoptosis deficiency of cancer cells is also of great
      therapeutic importance. MATERIALS AND METHODS: Seven known pentacyclic
      triterpenes and one steroid were isolated from Euphorbia lagascae methanolic
      extracts and identified by physical and spectroscopic methods. These compounds,
      together with eleven terpenoids previously isolated from Euphorbia lagascae and
      E. tuckeyana were tested for their MDR-reversing and/or apoptosis induction
      activities by flow cytometry on L5178 human MDR1 gene-transfected mouse lymphoma
      cells. RESULTS: Four taraxastane-type triterpenes: 21alpha-hydroxytaraxasterol,
      21alpha-hydroxytaraxasterol acetate, 3beta,30-dihydroxy-20(21)-taraxastene and
      3beta-hydroxy-20-taraxasten-30-al, and two steroids: stigmastane-3,6-dione and
      ergosterol peroxide exhibited a significant MDR-Pgp modulation activity. Some
      aspects of structure-activity relationships are discussed. Regarding apoptosis
      induction, the most significant results were obtained for the polycyclic
      diterpenes ent-16alpha,17-dihydroxykauran-3-one and ent-16alpha,17
      dihydroxyatisan-3-one.

PMID- 20032394
TI  - The anti-angiogenic activity of NSITC, a specific cathepsin L inhibitor.
AB  - Increased neovasculature and resistance to chemotherapy are hallmarks of
      aggressive cancer; therefore, the development of approaches to simultaneously
      inhibit these two processes is highly desirable. Previous findings from our
      laboratory have demonstrated that cathepsin L plays a key role in the development
      of drug resistance in cancer, and that its inhibition reversed this phenomenon.
      The goal of the present study was to determine whether targeting cathepsin L
      would inhibit angiogenesis. For this, the effects of a specific cathepsin L
      inhibitor, Napsul-Ile-Trp-CHO (NSITC), were tested in vitro on endothelial cell
      proliferation and interaction with the extracellular matrix, and also in vivo, by
      measuring its effect on angiogenesis in the chick chorioallantoic membrane (CAM)
      and mouse matrigel models. The results indicated that NSITC readily inhibits the
      proliferation of endothelial cells by inducing cell cycle arrest at the G(0)/G(1)
      phase, and suppresses cell adhesion to different substrates. Investigation of the
      underlying mechanism(s) indicated that NSITC was able to reduce expression of the
      adhesion molecule alphaVbeta3 integrin, inhibit cathepsin L-mediated degradation
      of the extracellular matrix, and disrupt secretion of the pro-angiogenic factors
      fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF).
      NSITC demonstrated potent efficacy in inhibiting growth factor- and tumor
      mediated-angiogenesis in the CAM and mouse matrigel models of angiogenesis. The
      anti-angiogenic effects of NSITC resulted in inhibition of tumor growth in the
      CAM and in nude mouse xenograft models. Together, these findings provide evidence
      that cathepsin L plays an important role in angiogenesis and suggest that NSITC
      represents a potential drug for the treatment of aggressive cancer.

PMID- 20032395
TI  - Numerical abnormalities of chromosome 9 and p16CDKN2A gene deletion detected by
      FISH in non-small cell lung cancer.
AB  - BACKGROUND: Lung cancer is one of the most common types of cancer worldwide and
      its pathogenesis is closely associated with various environmental exposures and
      gene alterations. The identification of genetic changes is a useful strategy
      toward understanding tumourigenesis and specific genetic associations. Since the
      tumor suppressor gene p16 located at 9p21 chromosomal region might have an
      important role in lung carcinogenesis, the aim of the present study was to
      investigate p16 gene alterations and numerical aberrations of chromosome 9 in non
      small cell lung cancer. MATERIALS AND METHODS: Nineteen cases of non-small cell
      lung cancer (11 squamous cell carcinomas, 6 adenocarcinomas and 2 large cell
      carcinomas) were investigated by fluorescence in situ hybridization (FISH)
      technique using a DNA p16 probe and alpha-satellite probe specific for chromosome
      9. RESULTS: Polysomy 9 was found in 13 cases (6/11 squamous cell carcinomas, 5/6
      adenocarcinomas and 2/2 large cell carcinomas). p16 gene alterations were found
      in 16 cases. Among them, deletion of p16 gene was found in 15 cases (8/11
      squamous cell carcinomas, 5/6 adenocarcinomas and 2/2 large cell carcinomas). In
      six cases with p16 gene deletion, homozygous deletion was observed. CONCLUSION:
      Numerical aberrations of chromosome 9 and p16 gene deletion are common findings
      in all subtypes of non-small cell lung cancer. Despite suggesting the p16 gene in
      the 9p chromosomal region plays a role in lung carcinogenesis, the presence of
      other oncogenes reflected by polysomy 9 participating in the neoplastic process
      cannot be excluded. Data of the present study also suggest, that there might not
      be a fundamental relationship between genetic changes and histological subtype of
      non-small cell lung cancer.

PMID- 20032396
TI  - Development and characterization of HAT-sensitive Ewing tumour cells for
      immunotherapy.
AB  - BACKGROUND: Despite improvements in the treatment of patients with Ewing family
      tumours (EFT) during the past decades, the prognosis for patients with advanced
      disease is still unsatisfying. New treatment strategies have to be developed.
      MATERIALS AND METHODS: A hypoxanthine/aminopterin/thymidine (HAT)-sensitive EFT
      cell line was developed by repetitive treatment of the EFT cell line SK-N-MC with
      8'-azaguanine (8AG). By using DNA microarrays, the gene expression profile of
      this cell line was characterized. Immunostimulatory activity was assessed by
      mixed lymphocyte/tumour cell culture (MLTC). Artificial fusion of tumour cells
      and dendritic cells was visualized by flow cytometry. RESULTS: After selection of
      8AG-resistant cells, a cell line with high sensitivity for treatment with HAT was
      obtained. Expression of the X chromosome inactivation specific transcript XIST
      was higher in HAT-sensitive cells. Nevertheless, HAT-sensitive cells retained the
      EFT-associated gene expression profile. Moreover, in the presence of HAT, it was
      possible to use these cells without irradiation as stimulatory cells in MLTC or
      as fusion partner for dendritic cells. CONCLUSION: HAT-sensitive EFT cells might
      be an interesting tool for the development of new immunotherapeutic approaches
      for the treatment of EFT.

PMID- 20032397
TI  - IL-6 regulates MMP-10 expression via JAK2/STAT3 signaling pathway in a human lung
      adenocarcinoma cell line.
AB  - We previously reported that matrix metalloproteinase (MMP)-10 mRNA levels were
      significantly lower in tumor tissues than in adjacent normal tissues in human non
      small cell lung cancer (NSCLC), whereas protein levels of MMP-10 were higher in
      the tumor tissues than the adjacent tissues. The mechanism of this divergence is
      still unknown. In the present study the role of Janus kinase 2/signal transducers
      and activators of transcription 3 (JAK2/STAT3) on interleukin (IL)-6 mediated
      regulation of MMP-10 expression was investigated in a human lung adenocarcinoma
      cell line (A549 cells) and the molecular regulatory mechanism of MMP-10
      expression was explored. A549 cells were stimulated by different concentrations
      of IL-6 with or without AG490, a specific JAK2 inhibitor. It was demonstrated
      that IL-6 moderately reduced the MMP-10 mRNA levels, whereas it significantly
      enhanced the MMP-10 protein mass in the A549 cells. This phenomenon mimicked the
      divergence of mRNA level and protein mass of MMP-10 in human NSCLC. Moreover, the
      present study indicated that IL-6 regulation of MMP-10 expression was via the
      JAK2/STAT3 pathway. STAT3 mRNA levels were significantly increased when the cells
      were treated with IL-6, whereas when AG490 (50 muM) was added to the cell
      cultures, IL-6-induced increase of STAT3 mRNA levels was abolished. Meanwhile,
      AG490 blocked the IL-6-induced inhibition of MMP-10 mRNA as well as blocking the
      IL-6-induced increase of MMP-10 protein mass in the A549 cells. Neither IL-6 nor
      AG490 influenced JAK2 mRNA levels in the A549 cell cultures. It is concluded that
      the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and
      IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10
      protein mass in human lung adenocarcinoma A549 cells. Contrasting effects of IL-6
      on MMP-10 mRNA level and protein concentration in A549 cells may partially
      explain the divergence of MMP-10 mRNA level and protein mass in human NSCLC.

PMID- 20032398
TI  - Aloe-emodin induces cell death through S-phase arrest and caspase-dependent
      pathways in human tongue squamous cancer SCC-4 cells.
AB  - Aloe-emodin, one of the anthraquinones, has been shown to have anticancer
      activity in different kinds of human cancer cell lines. Therefore, the purpose of
      this study was to investigate the anti-cancer effect of aloe-emodin on human
      tongue squamous carcinoma SCC-4 cells. The results indicated that aloe-emodin
      induced cell death through S-phase arrest and apoptosis in a dose- and time
      dependent manner. Treatment with 30 microM of aloe-emodin led to S-phase arrest
      through promoted p53, p21 and p27, but inhibited cyclin A, E, thymidylate
      synthase and Cdc25A levels. Aloe-emodin promoted the release of apoptosis
      inducing factor (AIF), endonuclease G (Endo G), pro-caspase-9 and cytochrome c
      from the mitochondria via a loss of the mitochondrial membrane potential
      (DeltaPsi(m)) which was associated with a increase in the ratio of B-cell
      lymphoma 2-associated X protein (Bax)/B cell lymphoma/leukemia-2 (Bcl-2) and
      activation of caspase-9 and -3. The free radical scavenger N-acetylcysteine (NAC)
      and caspase inhibitors markedly blocked aloe-emodin-induced apoptosis. Aloe
      emodin thus induced apoptosis in the SCC-4 cells through the Fas/death-receptor,
      mitochondria and caspase cascade. Aloe-emodin could be a novel chemotherapeutic
      drug candidate for the treatment of human tongue squamous cancer in the future.

PMID- 20032399
TI  - Establishment of imageable model of T-cell lymphoma growing in syngenic mice.
AB  - BACKGROUND: Cancer research is focused on processes which influence in vivo tumor
      growth dynamics, tumor microenvironment and antitumor immune responses. Recently,
      it was documented that some cytostatics, including their polymeric derivatives,
      were able to trigger an anticancer immune response. Such interactions are studied
      mainly in vitro but relevant in vivo studies are necessary and were only recently
      started. Whole-body imaging of fluorescently labeled tumors, which enables
      visualization of the whole-body down to single cell-cell interactions, is
      therefore a promising tool in understanding these processes. MATERIALS AND
      METHODS: EL-4 T-cell lymphoma cells were transfected with plasmid containing
      either fusion construct of enhanced green fluorecent protein (EGFP) with H2B
      histone or pure EGFP gene under cytomegalovirus promotor and resistance to
      neomycin. Stability of expression was determined by flow cytometry and cellular
      localization of green fluorescence signal was tested using fluorescent
      microscopy. An in vivo whole-body imaging system was used to evaluate growth in
      vivo. RESULTS: EL-4 cells were successfully transfected and established stable
      transfectants with a proliferation rate comparable to that of wild-type EL-4.
      Clone 12, with very strong whole-cell expression, enables tracking of metastatic
      spreading, whereas clone 3, with EGFP within the cell nucleus, allows frozen
      section analysis and observing of interaction with immunocompetent cells.
      CONCLUSION: Established imageable EL-4-EGFP(+) cell lines are a magnificent tool
      for the study of tumor growth and the tumor microenvironment.

PMID- 20032400
TI  - Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human
      medullary thyroid carcinoma cells.
AB  - Medullary thyroid carcinoma (MTC), a rare calcitonin-producing tumor, is derived
      from parafollicular C-cells of the thyroid and is characterized by constitutive
      Bcl-2 overexpression. The tumor is relatively insensitive to radiation therapy as
      well as conventional chemotherapy. To date, the only curative treatment is the
      early and complete surgical removal of all neoplastic tissue. In this study, the
      antiproliferative and pro-apoptotic effects of fractions obtained from Uncaria
      tomentosa (Willd.) DC, commonly known as una de gato or cat's claw were
      investigated. Cell growth of MTC cells as well as enzymatic activity of
      mitochondrial dehydrogenase was markedly inhibited after treatment with different
      fractions of the plant. Furthermore, there was an increase in the expressions of
      caspase-3 and -7 and poly(ADP-ribose) polymerase (PARP) fraction, while bcl-2
      overexpression remained constant. In particular, the alkaloids isopterpodine and
      pteropodine of U. tomentosa exhibited a significant pro-apoptotic effect on MTC
      cells, whereas the alkaloid-poor fraction inhibited cell proliferation but did
      not show any pro-apoptotic effects. These promising results indicate the growth
      restraining and apoptotic potential of plant extracts against neuroendocrine
      tumors, which may add to existing therapies for cancer.

PMID- 20032401
TI  - Role of the pharmaceutical excipients in the tamoxifen activity on MCF-7 and vero
      cell cultures.
AB  - BACKGROUND: Microparticles are used for controlled drug delivery. With the aim of
      improving both bioavailability and tamoxifen selective toxicity, the activity of
      tamoxifen embedded in calcium alginate/chitosan microparticles was studied.
      MATERIALS AND METHODS: Tamoxifen alone and embedded in microparticles prepared
      with sodium alginate from Kelco (62% mannuronic acid and 38% guluronic acid) and
      from Fluka (30% mannuronic acid and 70% guluronic acid) was added to MCF-7 and
      Vero cultures and evaluated for antiproliferative activity by the MTT test.
      RESULTS: The use of Kelco or Fluka alginate resulted in different LD(50) values
      on Vero and MCF-7 cultures, showing a higher cytotoxicity toward Vero cells
      treated with tamoxifen embedded in Kelco microparticles (25 microM vs. 48 microM
      on MCF-7 cells) but a selective toxicity with Fluka microparticles (25 microM and
      10 microM on Vero and MCF-7 cells respectively). CONCLUSION: Microparticle
      formulation may improve selective toxicity according to the alginate employed:
      differences in the chemical alginate composition can dramatically change both
      drug activity and toxicity.

PMID- 20032402
TI  - Significance of methylation status and the expression of RECK mRNA in lung tissue
      of patients with NSCLC.
AB  - OBJECTIVES: RECK (reversion-inducing cysteine-rich protein with Kazal motifs) is
      a glycoprotein which negatively regulates the activity of matrix
      metalloproteinases (MMPs). We analyzed differences in RECK mRNA expression in
      histological types of non-small cell lung cancer (NSCLC) and the relationship
      between promoter methylation status of RECK gene, level of RECK mRNA expression
      and clinicopathological values of patients with NSCLC. PATIENTS AND METHODS:
      Methylation status of the promoter and the expression of RECK mRNA were analyzed
      in paired tissue samples (tumor and control) of 50 patients with NSCLC. The
      methylation status of the RECK promoter was assessed using methylation-specific
      PCR. The level of RECK mRNA expression was measured using an RT real-time PCR
      method. RESULTS: Lower expression of RECK mRNA in NSCLC tissue was recorded
      compared to normal tissue (p=0.0032). Significantly lower expression of RECK in
      squamous cell carcinoma (SCC) tissue was observed in comparison with
      adenocarcinoma tissue (p=0.0051). Significant differences in expression of RECK
      in stages IB-IIIA were found in comparison with stage IA (p=0.0455). There was a
      significantly lower expression of RECK mRNA in NSCLC tissue in samples with
      positive RECK promoter methylation status in comparison with samples with
      negative promoter methylation status (p=0.0400). CONCLUSION: We showed that there
      were differences in expression between histological types of NSCLC (SCC,
      adenocarcinoma). There was a higher expression of RECK in stage IA in comparison
      with stages IB-IIIA. Our results indicate that RECK could be classified as a
      tumor suppressor gene and is an interesting target for further investigation of
      MMP inhibitors.

PMID- 20032403
TI  - Catalase protects tumor cells from apoptosis induction by intercellular ROS
      signaling.
AB  - Transformed cells are subject to intercellular induction of apoptosis by
      neighbouring nontransformed cells and to autocrine apoptotic self-destruction.
      Both processes depend on extracellular superoxide anion generation by the
      transformed cells and on the release of peroxidase from both nontransformed and
      transformed cells. This concerted action results in HOCl synthesis, HOCl
      superoxide anion interaction and generation of apoptosis-inducing hydroxyl
      radicals. In contrast to transformed cells, ex vivo tumor cells are resistant
      against intercellular induction of apoptosis and autocrine apoptotic self
      destruction. Resistance of tumor cells against intercellular ROS signaling
      depends on interference through catalase expression on the membrane.
      Intercellular ROS signaling of tumor cells can be restored when i) exogenous HOCl
      is added; ii) exogenous hydrogen peroxide is supplied, or iii) catalase is
      inhibited. These findings define the biochemical basis for specific apoptosis
      induction in tumor cells through re-establishment of intercellular ROS signaling,
      a potential novel approach in tumor prevention and therapy.

PMID- 20032404
TI  - Modulation of intercellular ROS signaling of human tumor cells.
AB  - Tumor cells are resistant against apoptosis-inducing intercellular reactive
      oxygen species (ROS) signaling but can be resensitized by the inhibition of
      catalase. Hydrogen peroxide exhibits a dual role in the modulation of
      intercellular ROS signaling. When suboptimal concentrations of the catalase
      inhibitior 3-aminotriazole (3-AT) are applied, additional exogenous hydrogen
      peroxide shifts apoptosis induction to its optimum. When hydrogen peroxide is
      added at optimal concentrations of 3-AT, or when higher concentrations of 3-AT
      are applied, the subsequent consumption between HOCl and hydrogen peroxide blunts
      overall apoptosis induction. These supraoptimal conditions can be brought back to
      the optimum through excess myeloperoxidase (MPO), partial removal of hydrogen
      peroxide through the catalase mimetic EUK-134 or partial inhibition of NADPH
      oxidase. Exogenous nitric oxide (NO) interferes with HOCl signaling through
      consumption of hydrogen peroxide. Site-specific generation of hydroxyl radicals
      at the cell membrane of tumor cells induces apoptosis, whereas random HOCl
      superoxide anion interaction, and ferrous iron-induced Fenton chemistry of HOCl
      inhibit intercellular ROS signaling.

PMID- 20032405
TI  - Reduction of oxidative DNA fragmentation by ascorbic acid, zinc and N
      acetylcysteine in nasal mucosa tissue cultures.
AB  - Oxidative stress is one major factor in upper aerodigestive tract carcinogenesis.
      Reactive oxygen species derived from environmental sources, cigarette smoke or
      cellular metabolism, constantly attack large molecules within the cell. While
      damaged lipids and proteins can be replaced, oxidative DNA damage needs to be
      repaired. Damage exceeding DNA repair capacity might lead to permanent mutations.
      Ascorbic acid, zinc and N-acetylcysteine are widely used as supplementations
      during upper aerodigestive tract infections. Therefore we chose to investigate
      their potential in DNA protection. We produced so called "mini-organ" cultures of
      nasal mucosa, three-dimensional tissue cubes coated with ciliated epithelium, for
      repeated incubation with ascorbic acid, zinc and N-acetylcysteine at different
      concentrations. This model has several advantages with respect to repeated
      incubations, metabolic competence of cells and standardized conditions compared
      to cell line experiments or animal models. After washing twice, oxidative damage
      was induced by hydrogen peroxide. Resulting DNA fragmentation was analyzed using
      the FPG-comet assay, a special modification of the alkaline single-cell microgel
      electrophoresis for the detection of the most prevalent oxidative DNA base
      modification. DNA damage was reduced within a range of 45-60%. Cell viability
      after incubations with hydrogenperoxide was >90%. Our results show strong DNA
      protective effects of the substances tested in accordance with epidemiological
      studies linking a diet rich in antioxidative micronutrients with a lowered risk
      for cancer development. The reasons for the failure of large antioxidant
      supplementation interventional trials need to be further investigated.

PMID- 20032406
TI  - Influence of imatinib mesylate on radiosensitivity of astrocytoma cells.
AB  - Imatinib mesylate (STI571), an inhibitor of alpha- and beta-platelet-derived
      growth factor receptors (PDGFR) and other tyrosine kinases, is a well established
      treatment for chronic myeloid leukaemia and gastrointestinal stromal tumours.
      Moreover, it is under investigation for the therapy of several other malignant
      tumours since protein kinases are frequently mutated or otherwise deregulated in
      human malignancies and they serve as a target for differentiating between tumour
      cells and normal tissues. The objective of this study was to determine whether
      gamma radiation could sensitize astrocytoma cell lines to the effects of imatinib
      in vitro. For this purpose, T98G and MOG-G-UVW astrocytoma cells were treated
      with imatinib alone or in combination with gamma radiation. The clonogenic
      survival assays performed with the combination of imatinib with radiation
      demonstrated that the drug had an additive antiproliferative effect in both cell
      lines considered. Imatinib confered greater radiosensitivity on the T98G tumour
      cells effecting a significant decrease in colony formation compared with
      radiation alone. These data provide a rationale to further investigate the
      combination of imatinib with radiation, keeping in mind that this may result in
      unexpected toxicities that are not observed with either treatment alone.

PMID- 20032407
TI  - In vitro effects of dichloroacetate and CO2 on hypoxic HeLa cells.
AB  - HeLa and PANC-1 cells were exposed to conflicting signals promoting anaerobic or
      aerobic energy-generating processes and their viability, cell numbers and the
      ability of HeLa cells to form colonies were assessed. Under conventional aerobic
      cell culture with 5% CO(2), dichloroacetate (DCA), an inhibitor of the enzyme
      pyruvate dehydrogense kinase with subsequent stimulation of pyruvate
      dehydrogenase that redirects energy metabolism toward the Kreb cycle, reduced
      HeLa and PANC-1 cellular proliferation and viability. With nitrogen-induced
      hypoxia, the number of control cells and cells cultured with 12.5 mM DCA
      paradoxically was greater than that of normoxic controls under similar
      conditions. A higher medium pH of cells cultured under nitrogen contributed to
      these differences. In 96-well experiments, 95% nitrogen with 5% CO(2) reduced the
      numbers of hypoxic cells and medium pH toward that of the aerobic controls, with
      retention of the DCA-induced hypoxic compared to normoxic cell numbers. The media
      of these cells cultured with DCA still exhibited an increased pH. Increased
      hypoxia-inducible factor 1, alpha subunit (HIF1A) mRNA expression in hypoxic HeLa
      cells and their greater reliance on D-glucose for metabolic energy confirmed the
      reliability of the incubation conditions. Compared with normoxic cells, hypoxic
      cells initially increased their synthesis of ATP, but once proliferation ceased,
      this no longer closely correlated with cell numbers. Type 1 apoptosis, which was
      somewhat greater in hypoxic than normoxic cells, contributed to hypoxia and DCA
      induced cell death. Colony counts of hypoxic, DCA-inhibited cells subsequently
      switched to normoxia exceeded those of similarly treated normoxic DCA cells.
      Despite inhibition in certain hypoxic environments of pyruvate dehydrogenase
      kinase by DCA and its contribution to increased cellular apoptosis and necrosis,
      hypoxic cells generally outnumbered normoxic control cells, as did hypoxic DCA
      treated cells compared with comparable DCA-treated normoxic cells. Since in vivo
      hypoxic cells are considered a major factor contributing to therapeutic failure,
      and as DCA redirects energy metabolism toward the more energy efficient Kreb
      citric acid cycle, associated with increased medium (and inferred cellular) pH,
      similar circumstances in vivo could promote proliferation and survival of hypoxic
      cell clones with the potential for developing unwanted properties.

PMID- 20032408
TI  - The cytotoxic effects of gemtuzumab ozogamicin (mylotarg) in combination with
      conventional antileukemic agents by isobologram analysis in vitro.
AB  - BACKGROUND: The CD33 antigen is expressed on leukemia cells in most patients with
      acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL), and in 20%
      of patients with acute lymphoblastic leukemia (ALL), while it is absent from
      pluripotent hematopoietic stem cells and nonhematopoietic cells. Gemtuzumab
      ozogamicin (GO) is an immunoconjugate of an anti-CD33 antibody linked to
      calicheamicin, which is a potent cytotoxic agent that causes double-strand DNA
      breaks, resulting in cell death. GO was developed against CD33 antigen-positive
      leukemias. The aim of this study was to investigate the cytotoxic effects of this
      agent in combination with conventional antileukemic agents. MATERIALS AND
      METHODS: The cytotoxic effects of GO in combination with antileukemic agents were
      studied against human CD33 antigen-positive leukemia HL-60, U937, TCC-S and
      NALM20 cells. The leukemia cells were exposed simultaneously to GO and to the
      other agents for 4 days. Cell growth inhibition was determined using a MTT
      reduction assay. The isobologram method was used to evaluate the cytotoxic
      interaction. RESULTS: GO produced synergistic effects with mitoxantrone, additive
      effects with cytarabine, daunorubicin, idarubicin, doxorubicin, etoposide and 6
      mercaptopurine, and antagonistic effects with methotrexate and vincristine.
      CONCLUSION: Our findings suggest that the simultaneous administration of GO with
      most agents studied would be advantageous for antileukemic activity. The
      simultaneous administration of GO with methotrexate or vincristine would have
      little cytotoxic effect, and this combination may be inappropriate. These
      findings may be useful in clinical trials of combination chemotherapy including
      GO or other monoclonal antibodies linked to calicheamicin.

PMID- 20032410
TI  - Postoperative radiotherapy for localized prostate cancer: clinical significance
      of nadir prostate-specific antigen value within 12 months.
AB  - AIM: To analyze retrospectively the results of postoperative radiotherapy for
      localized prostate cancer and to investigate the clinical significance of nadir
      prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early
      estimate of clinical outcome after radiotherapy. PATIENTS AND METHODS: Seventy
      six patients with localized prostate cancer treated with postoperative
      radiotherapy were retrospectively reviewed. Total radiation doses ranged from 50
      to 70 Gy (median: 60 Gy), and the median follow-up period for all 76 patients was
      47.9 months (range, 12.4-101.3 months). RESULTS: The 5-year actuarial overall
      survival, progression-free survival, biochemical relapse-free survival (BRFS) and
      local control rates in all 76 patients after radiotherapy were 86.1%, 77.8%,
      80.0% and 92.2%, respectively. Distant metastases and/or regional lymph node
      metastases developed in 11 patients (14%) after radiotherapy, while local
      progression was observed in only 5 patients (7%). Of all 76 patients, the median
      nPSA12 in patients with biochemical failure and that in patients without
      biochemical failure were 1.16 ng/ml and 0.05 ng/ml, respectively. The 5-year BRFS
      rates in patients with low nPSA12 (<0.5 ng/ml) and those with high nPSA12 (> or
      =0.5 ng/ml) were 92.7% and 42.2%, respectively (p<0.0001). In univariate
      analysis, nPSA12, pre-radiotherapy PSA, Karnofsky performance status and the use
      of chemotherapy had a significant impact on BRFS, and in multivariate analysis,
      nPSA12 alone was an independent prognostic factor for BRFS. CONCLUSION:
      Postoperative radiotherapy results in an excellent local control rate for
      localized prostate cancer and nPSA12 is predictive of biochemical failure after
      postoperative radiotherapy.

PMID- 20032409
TI  - Reversal of P-gp-mediated multidrug resistance by Bromotetrandrine in vivo is
      associated with enhanced accumulation of chemotherapeutical drug in tumor tissue.
AB  - BACKGROUND: Our previous studies have shown that tetrandrine (Tet) reverses the
      effect of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) both in vitro
      and in vivo. 5-Bromotetrandrine (Br-Tet) is a newly synthesized brominated
      derivative of Tet. In this study, we investigated the MDR reversal activity of Br
      Tet in vitro and in vivo and the mechanism involved in this reversal. MATERIALS
      AND METHODS: The ability of Br-Tet to reverse drug resistance in vitro was
      evaluated by MTT assay in human MDR KBv200 cells and the parental drug-sensitive
      KB cells. A KBv200 cell xenograft model was established to investigate the MDR
      reversal activity of Br-Tet in vivo. Doxorubicin (Dox) accumulation in KBv200 and
      KB cell lines was determined by flow cytometry and Dox accumulation in KBv200
      xenografts tissue was examined by spectrofluorometer. The effect of Br-Tet on the
      expression of P-glycoprotein was detected by flow cytometry and Western blot,
      respectively. RESULTS: Br-Tet significantly enhanced the cytotoxicity of Dox,
      paclitaxel, taxotere, vincristine and epirubicin in KBv200 cells but not in KB
      cells. Co-administration of 10 mg/kg Br-Tet and 2 mg/kg epirubicin significantly
      enhanced the antitumor activity of epirubicin without increasing the toxicity. Br
      Tet increased the Dox accumulation in the MDR KBv200 cell line and in KBv200
      xenograft tissue in a time- and dose-dependent manner. However, it did not reduce
      the expression of P-gp in KBv200 cells. CONCLUSION: Br-Tet caused a significant
      reversal of P-gp-mediated MDR, not only in vitro but also in vivo. The MDR
      reversal activity of Br-Tet in vivo was associated with the enhancement of
      accumulation of chemotherapeutical drugs in tumor tissue.

PMID- 20032411
TI  - Ibadronate may prevent colorectal carcinogenesis in mice with ulcerative colitis.
AB  - An increased incidence of colorectal carcinoma is known to occur in patients with
      ulcerative colitis, which displays a cycle of recurrence-remission in the
      colorectal mucosa. Repeated oral doses of 3% dextran sulfate sodium subsequent to
      a single intraperitoneal injection of azoxymethane induces chronic ulcerative
      colitis, resulting in an increased incidence of high-grade dysplasia and
      submucosal-invasive adenocarcinomas in the mouse colorectum. The features of the
      colitis induced in this animal model are very similar to the ulcerative colitis
      in patients in terms of both clinical and histopathological characteristics.
      Bisphosphonates are known to increase bone mass by suppressing bone turnover in
      postmenopausal women. A novel single-nitrogen bisphosphonate, ibandronate, is
      effective in preventing skeletal events in patients with bone metastases from
      colorectal cancer. Decreasing the bone mineral affinity of bisphosphonates is an
      effective therapeutic strategy to inhibit skeletal tumor growth in vivo. In the
      present study, the preventative effects of the bisphosphonate ibadronate on
      colorectal carcinogenesis in mice treated with azoxymethane and dextran sulfate
      sodium was investigated. Additive treatment with bisphosphonate prevented the
      shrinkage of colorectum which was affected by a cycle of recurrence-remission in
      colorectal mucosa, resulting in a reduced incidence of colorectal dysplasia and a
      reduced expression of thymidine kinase mRNA in the colorectum. Taken together,
      the present results indicate that ibadronate may inhibit colorectal
      carcinogenesis and its development by inhibiting colorectal epithelial cell
      proliferation and the neoplastic process.

PMID- 20032412
TI  - Mitogenic activity of zeranol in human breast cancer cells is enhanced by leptin
      and suppressed by gossypol.
AB  - BACKGROUND: The molecular links between breast cancer and obesity have been
      studied for many years. Obesity significantly increases the incidence rate and
      chance of morbidity of breast cancer. Leptin, mainly secreted by adipocytes,
      plays an important role in breast cancer development. Leptin expression is up
      regulated in obesity and it can promote breast cancer cell growth. Zeranol is
      used as an anabolic growth promoter to stimulate cattle growth in the U.S. beef
      industry. (-)-Gossypol, a natural polyphenolic compound extracted from
      cottonseed, is an anticancer chemopreventive agent. MATERIALS AND METHODS:
      Zeranol, leptin and (-)-gossypol were used to investigate MCF-7 Adr cell growth.
      RESULTS: Leptin enhanced the sensitivity of MCF-7 Adr cells to zeranol and
      increased cell growth. Exposure to zeranol may lead to initiation of
      transformation of normal breast cells to breast preneoplastic cells. CONCLUSION:
      It is suggested that obese individuals may be at greater risk of developing
      zeranol-induced breast cancer.

PMID- 20032413
TI  - Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells.
AB  - BACKGROUND: Hedgehog (Hh) and Wnt signaling pathways are involved in the
      stimulation of growth of leukemia and lymphoma cells. In the present study,
      whether or not the Hh inhibitor, cyclopamine, and the Wnt inhibitor, quercetin,
      suppress cell growth was investigated. MATERIALS AND METHODS: The effects of
      cyclopamine and quercetin on the in vitro growth and protein expression of ten
      acute leukemia and B-cell lymphoma cell lines were examined. RESULTS: Cyclopamine
      and quercetin suppressed cell growth and induced apoptosis in seven and eight
      cell lines respectively. Cyclopamine decreased the level of Gli1 protein, a
      target gene product of Hh signaling. Quercetin decreased the level of Notch1
      protein and its active fragment in the DND-41 T-lymphoblastic leukemia cell line
      with constitutive Notch activation. CONCLUSION: Cyclopamine and quercetin
      suppress the growth of a number of leukemia and lymphoma cells. This finding
      suggests the potential use of these compounds in molecularly-targeted therapy for
      leukemia and lymphoma.

PMID- 20032414
TI  - Ovarian renin--angiotensin system-regulating aminopeptidases are involved in
      progesterone overproduction in rats with mammary tumours induced by N-methyl
      nitrosourea.
AB  - A local renin-angiotensin system (RAS) has been found in ovary. This ovarian RAS
      may regulate ovarian steroidogenesis. Ample studies show that the ovarian
      hormones estradiol (E2) and progesterone (P) are strongly implicated in the
      development of breast cancer. MATERIALS AND METHODS: The aim of the present work
      was to elucidate if alterations in ovarian RAS, analyzed through their
      proteolytic regulatory enzymes aminopeptidase A (APA), B (APB) and N (APN), could
      be responsible for an altered steroidogenesis in rats with mammary tumours
      induced by N-methyl nitrosourea (NMU). RESULTS: We describe here a highly
      significant increase of serum P levels in NMU-treated rats, concomitantly with an
      increase in ovarian aspartyl and glutamyl aminopeptidase activities (named
      together as APA activity). Moreover, we did not find changes in APB or APN
      activities, suggesting an increased metabolism from Ang II to Ang III and a
      decreased catabolism of Ang III. CONCLUSION: The relationship between ovarian RAS
      and P overproduction in a rat model of mammary carcinogenesis indicates ovarian
      RAS as a new potential target in breast cancer therapy.

PMID- 20032415
TI  - The Akt and ERK activation by platinum-based chemotherapy in ovarian cancer is
      associated with favorable patient outcome.
AB  - AIM: To investigate the phosphatidylinositol 3-kinase (PI3K)-Akt and
      extracellular signal regulated protein kinase (ERK) activation by chemotherapy,
      and the relationship between the activation of them and patient outcomes. The
      effect of chemotherapy on the cell proliferation and apoptosis markers and their
      role in the biology of ovarian cancer were also investigated. MATERIALS AND
      METHODS: This study was carried out in a series of 10 ovarian (or tubal) cancer
      patients whose specimens were obtained before and after chemotherapy. PI3K-Akt
      and ERK activation were evaluated by immunohistochemical staining for
      phosphorylated Akt and ERK. Their correlation with patient outcome was
      investigated by survival curves using the Kaplan-Meier method. Cell proliferation
      was evaluated by Ki-67 expression using immunofluorescent staining. Apoptosis was
      examined by caspase-3 and cleaved Poly ADP ribose polymerase (PARP) using
      immunofluorescent staining. RESULTS: An increase in Akt and ERK phosphorylation
      after chemotherapy was observed in 5 and 8 patients, respectively out of 10
      patients examined. Akt and ERK activation by chemotherapy were associated with a
      favorable overall survival. In almost all patients, Ki-67 expression was
      initially high and largely decreased after chemotherapy. An increase in apoptotic
      marker expression was observed in almost all patients exposed to chemotherapy.
      CONCLUSION: Our findings suggest that Akt and ERK activation by chemotherapy may
      be associated with favorable prognosis.

PMID- 20032416
TI  - BCL6-translocations affect the phenotype of follicular lymphomas only in the
      absence of t(14;18)IgH/BCL2.
AB  - BACKGROUND: The translocation t(14;18)IgH/BCL2 is the molecular hallmark of
      follicular lymphomas (FL). A subset of cases harbours translocations involving
      the BCL6-gene locus. This study aimed to determine the frequency of BCL2- and
      BCL6-translocations in FL and to identify morphological and immuno-histochemical
      features with respect to the presence of BCL2- and BCL6-translocations. MATERIALS
      AND METHODS: Fluorescence-in-situ-hybridisation (FISH) was used to determine the
      BCL2- and BCL6-translocation status of 102 FL and these were compared to
      morphological and immunohistochemical parameters. RESULTS: Lymphomas with BCL6-
      and BCL2-translocations were very similar to t(14;18)-positive lymphomas without
      BCL6-translocations. In contrast, t(14;18)-negative lymphomas with BCL6
      translocations were amongst others of higher grade, less often CD10-positive,
      involved the bone marrow less frequently and did not infiltrate the lymph node
      capsule. CONCLUSION: BCL2- and BCL6-translocations correlate with particular
      phenotypes of follicular lymphomas. BCL6-translocations seem to affect the
      phenotype only when they are not accompanied by BCL2-translocations.

PMID- 20032417
TI  - The arylhydrocarbon receptor is only marginally involved in the antileukemic
      effects of its ligand curcumin.
AB  - BACKGROUND: Acute myeloid leukaemia (AML) continues to present demanding
      treatment challenges, as in general the prognosis for long-term survival remains
      dire for the patients. Natural plant-derived substances with antileukemic
      properties offer new treatment possibilities or may act as by-stander therapy.
      Their molecular mechanisms of action are often not entirely clear, limiting
      theory-directed screening and application strategies. The plant substance
      curcumin is a known activator of the transcription factor aryl hydrocarbon
      receptor (AhR), and has well-documented antileukemic effects. The AhR regulates
      cell processes, including cell cycle and apoptosis. We ask here whether direct
      AhR-activation by curcumin contributes to its antileukemic/apoptotic potential.
      MATERIALS AND METHODS: The induction of caspases 3/7, 8, and 9, the breakdown of
      mitochondrial transmembrane potential, the BCL-2/BAX ratio, and the DNA content
      of cells were measured as indicators of apoptosis. In addition, the induction of
      cell cycle inhibitors p21 and p27 were assessed. RESULTS: While triggering of AhR
      signalling by curcumin in HL-60 cells was confirmed, induction of the above
      apoptosis parameters was not blocked by two AhR antagonists, alpha-naphtoflavone
      (alphaNF) and 3'-methoxy-4'nitroflavone (MNF). Only a moderate (20%) AhR
      dependent induction of caspases 3/7 was detectable. Interestingly,
      transcriptional changes induced by curcumin and by anticarcinogenic 1,25
      dihydroxy vitamin D3 overlapped by one third. CONCLUSION: We conclude that AhR is
      only marginally involved in the antileukemic effects of its ligand curcumin.

PMID- 20032418
TI  - Long-term eradication of locally recurrent invasive follicular thyroid carcinoma
      after taxane-based concomitant chemoradiotherapy.
AB  - A 46-year-old woman with history of radioiodine-refractory follicular thyroid
      carcinoma (FTC) presented with locally recurrent, high-risk, invasive disease.
      She was treated with paclitaxel/carboplatin concomitant chemoradiotherapy (CRT),
      which was well tolerated, resulting in complete remission and freedom from
      residual or recurrent FTC for longer than 5 years until her last follow-up at age
      52. This case highlights the possibility of combining taxane-based chemotherapy
      with definitive radiotherapy (as CRT) for the management of locally aggressive
      recurrences in poorly differentiated thyroid carcinoma, thereby resulting in
      rapid and persistent disease eradication. Even in the light of recent data on the
      potential benefit of novel targeted therapy agents in poorly differentiated
      thyroid carcinoma, this approach in similar clinical settings deserves future
      investigation.

PMID- 20032419
TI  - Differential expression of CD3zeta message and protein in tumor infiltrating
      lymphocytes from solid tumor specimens and malignant ascites from patients with
      ovarian carcinoma.
AB  - The expression of the CD3zeta subunit was investigated in fresh (uncultured)
      tumor-infiltrating lymphocytes (TILs) isolated from either solid tumor (ST)
      specimens or ascites (ASC) from patients with epithelial ovarian carcinoma (EOC).
      Western blot analysis of CD3zeta immunoprecipitates using anti-CD3zeta rabbit
      serum revealed that in 6 out of 6 patients with EOC, the CD3zeta protein was
      absent from ST-TILs. Immunoprecipitation with anti-phosphotyrosine monoclonal
      antibody (anti-PY20) from ST-TILs from one patient revealed bands co-migrating
      with the phosphorylated CD3zeta. CD3zeta protein was found to be expressed in
      only 1 out of 7 ST-TILs from patients with EOC. ASC-TILs were available in 5 of
      these patients and immunoprecipitation/Western blotting experiments using anti
      CD3zeta rabbit serum revealed that CD3zeta protein was expressed in all 5. In
      addition, CD3zeta protein was expressed in 3 additional ASC-TIL specimens for
      which ST-TILs were not available. Therefore, the CD3zeta protein was expressed in
      ASC-TIL isolated from 8 out of 8 patients with EOC. CD3zeta protein was also
      expressed on peripheral blood mononuclear cells (PBMCs) from patients with EOC
      and from normal donors. RT-PCR studies of fresh ST-TIL specimens, using CD3zeta
      specific primers, revealed that CD3zeta transcripts were absent from 13 out of 21
      patients with EOC, down-regulated in 4 patients and present at levels comparable
      to those found in PBMCs in 4 other patients. In contrast, CD3delta transcripts
      were present at comparable levels in all specimens. Treatment with recombinant
      interleukin-2 (rIL-2) (600 IU/ml) restored the expression of CD3zeta protein and
      transcripts in cultured ST-TILs, whereas fresh ST-TILs did not express CD3zeta,
      in contrast to fresh ASC-TILs. These results demonstrate differential expression
      of CD3zeta in ST-TILs versus ASC-TILs in patients with EOC. CD3zeta transcripts
      and protein were found to be absent from most ST-TILs from patients with EOC,
      whereas they were expressed in ASC-TILs and PBMCs from such patients.

PMID- 20032420
TI  - Altered glucose metabolism during chemoradiation for head and neck cancer.
AB  - Platinum-based chemotherapy has been reported to induce diabetes and hyperosmolar
      coma in nondiabetic patients. The aim of the present study was to determine
      whether the administration of chemoradiation for head and neck carcinoma alters
      glucose metabolism during and after treatment. PATIENTS AND METHODS: Weekly
      nonfasting serum glucose level was obtained during treatment of one hundred and
      six patients with locally advanced head and neck cancer who underwent
      chemoradiationt. RESULTS: For the 91 non-diabetic patients, mean serum glucose
      level measured 97.75 before and 102.1, 102, 104.1, 109.1, 109.7, 110.3, 109.8,
      113.2, 107.7 and 104.3 mg/dl during weeks 1-10 of treatment respectively. Serum
      glucose level elevation reached statistical significance for weeks 5-8.
      CONCLUSION: Chemoradiation for head and neck cancer may produce severe glucose
      metabolism alteration during treatment.

PMID- 20032421
TI  - Preoperative chemotherapy with S-1 and cisplatin for highly advanced gastric
      cancer.
AB  - Feasibility and efficacy of S-1 and cisplatin followed by surgery was evaluated,
      and factors contributing to survival benefit were analyzed. PATIENTS AND METHODS:
      In total, 120 consecutive patients with highly advanced gastric cancer were
      treated with S-1 (80 mg/m(2) for 21 consecutive days) and cisplatin (50 mg/m(2)
      on day 8). RESULTS: The response rate was 62.5% overall, and 75.7% for these with
      metastatic lymph nodes. Grade 3/4 adverse events were less than 10%. The median
      survival time was 41.9 months among 93 patients whose primary lesion was
      resected. Liver metastasis, R2 resection, poor performance status and lack of
      response were identified as independent risk factors by a multivariate analysis.
      CONCLUSION: Preoperative chemotherapy with S-1 and cisplatin was effective. The
      results show the need for different approaches in the treatment of patients with
      metastases and these without.

PMID- 20032422
TI  - Patients with clinical/radiological hyperplasia of mammary glands show
      pathological persistence of temperature of skin points.
AB  - BACKGROUND: Hyperplasia of mammary glands (HMG) is a frequent disease, with
      increased cancer risk for women aged 20-55 years. The aim of this study was to
      explore a non-invasive method to identify which patients with breast complaints
      need additional mammography for HMG diagnosis. PATIENTS AND METHODS: Skin digital
      infrared thermal imaging (DITI) in 74 patients with HMG and 63 controls was
      carried out. RESULTS: In the controls, the temperature of points close to the
      breasts and ovaries decreased with age. In women older than 39 years, HMG
      patients showed persistently high temperatures but in the lower extremities there
      were no differences. With a threshold for thoracic skin point KI21 of 33.2
      degrees C, sensitivity and specificity in distinguishing controls from HMGs were
      96% and 52% (p=0.0001) respectively, as validated in a test set, similar to
      recent DITI results for breast cancer detection. CONCLUSION: Infrared temperature
      imaging of specific skin points is a rapid, non-invasive method to identify
      patients requiring mammography to confirm HMG.

PMID- 20032423
TI  - Epithelial-myoepithelial carcinoma of the minor salivary glands:
      immunohistochemical and morphological features.
AB  - AIMS: Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland
      neoplasm that most commonly occurs in the parotid gland, but can also arise in
      the minor salivary glands. Three cases are reported of epithelial-myoepithelial
      carcinoma of the minor salivary glands, with the goal of better defining this
      entity. PATIENTS AND METHODS: All three cases showed a characteristic
      nodular/multinodular growth pattern and classic biphasic tubular histology. All
      parts of each tumor were surrounded by a myoepithelial cell rim and there was
      evidence of invasion. RESULTS: Immunohistochemical analysis showed the tumor
      cells to be weakly positive for S100, cytokeratin (CK) CK5/6, CK7, CKAE-1/AE-3
      and strongly positive for epithelial membrane antigen (EMA) and p63; they were
      focally positive for calponin and acute lymphoblastic leukemia antigen (CD10).
      The tumor cells were negative for vimentin, alpha-smooth muscle actin (SMA)
      (except one case), glial fibrillar acid protein (GFAP) and MIB1. The tumors were
      resected completely with wide margins and no recurrence or metastasis had
      occurred from 6 to 15 months after surgery. CONCLUSION: Three cases of minor
      salivary gland tumors are described and the differential diagnosis underlined in
      relation to benign myoepithelioma. The characteristic morphological and
      immunohistochemical features aided diagnosis of these biphasic tumors.

PMID- 20032424
TI  - Frozen section in axillary sentinel lymph nodes for diagnosis of breast cancer
      micrometastasis.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy plays a major role in the surgical
      management of primary breast cancer. The aim of this study was to assess the
      diagnostic accuracy of the assessment of axillary frozen sections of SLNs for
      micrometastasis diagnosis. PATIENTS AND METHODS: This study focused on 278 SLNs
      from 149 patients. Each lymph node was fully analyzed by frozen section. After
      fixation, serial sections were cut and stained by hematoxylin and eosin (HE) and
      for pan-cytokeratins by immunohistochemistry (IHC). RESULTS: Tumor cells were
      detected in 63 SLNs, 41 on frozen sections and 22 on controls. Of these 63
      positive SLNs, 42 contained metastases, 10 contained micrometastases and 11
      contained isolated tumor cells. The specificity and positive predictive value of
      SLN frozen sections for micrometastasis was 100%. The sensitivity was 83.3% for
      metastasis, 40% for micrometastasis; the false-negative rate was 16.7% for
      metastasis and 60% for micrometastasis. CONCLUSION: Analysis of frozen section of
      SLNs is an accurate method for metastasis detection, allowing concurrent axillary
      dissection when positive. The protocol for SLN analyses described herein shows
      good sensitivity for micrometastasis detection.

PMID- 20032425
TI  - Immunological similarities between cancer and chronic fatigue syndrome: the
      common link to fatigue?
AB  - Cancer and chronic fatigue syndrome (CFS) are both characterised by fatigue and
      severe disability. Besides fatigue, certain aspects of immune dysfunctions appear
      to be present in both illnesses. In this regard, a literature review of
      overlapping immune dysfunctions in CFS and cancer is provided. Special emphasis
      is given to the relationship between immune dysfunctions and fatigue.
      Abnormalities in ribonuclease (RNase) L and hyperactivation of nuclear factor
      kappa beta (NF-kappaB) are present in CFS and in prostate cancer. Malfunctioning
      of natural killer (NK) cells has long been recognised as an important factor in
      the development and reoccurrence of cancer, and has been documented repeatedly in
      CFS patients. The dysregulation of the RNase L pathway, hyperactive NF-kappaB
      leading to disturbed apoptotic mechanisms and oxidative stress or excessive
      nitric oxide, and low NK activity may play a role in the two diseases and in the
      physiopathology of the common symptom fatigue. However, in cancer the relation
      between the immune dysfunctions and fatigue has been poorly studied.
      Immunological abnormalities to such as a dysregulated RNase L pathway,
      hyperactive NF-kappaB, increased oxidative stress and reduced NK cytotoxicity,
      among others, are present in both diseases. These anomalies may be part of the
      physiopathology of some of the common complaints, such as fatigue. Further
      studies to confirm the hypotheses given here are warranted.

PMID- 20032426
TI  - Utility of a simplified molecular classification of tumors for predicting
      survival of patients with invasive ductal breast carcinoma.
AB  - BACKGROUND: In a recent report it was shown that molecular subgroups of early
      (pT1) breast tumors belonging exclusively to the most common histological
      variant, ductal-infiltrating carcinoma, showed significantly different clinical
      and biological features. OBJECTIVE: To test in a series of patients with ductal
      infiltrating carcinoma encompassing all stages of the disease if the above
      mentioned biological differences already detected at the earliest stage are
      ultimately reflected in survival differences. PATIENTS AND METHODS: All patients
      with ductal infiltrating carcinoma operated upon at Hospital de Mostoles, Madrid,
      Spain, between 1997 and 2002 were included into the study, to allow for at least
      five years of follow-up for survivors. Of 242 studied patients, according to the
      International Federation of Gynecology and Obstetrics (FIGO) classification,
      37.6% were in stage I, 47.2% in stage II, 11.0% in stage III, and 4.2% in stage
      IV. According to the simplified molecular classification of Carey et al., 116
      tumors (47.9%) expressed estrogen receptors, and did not express c-erb-B2
      (Luminal A), 67 (27.7%) coexpressed hormone receptors (either estrogen receptors,
      progesterone receptors or both) and c-erb-B2 (Luminal B), 33 (13.3%) expressed c
      erb-B2 in the absence of hormone receptors (HER-2), and 26 (10.7%) neither
      expressed hormone receptors, nor c-erb-B2 (triple-negative, basal). RESULTS: In a
      univariate model, both disease-free survival and overall survival of the patients
      were significantly associated with stage (p=0.0003; p<0.0001), histological grade
      (p<0.0001; p<0.0001), lymphatic vascular space invasion (p=0005; p=0.0044),
      menopausal status (p=0.04; p=0.034) and molecular subgrouping (p=0.037: p=0.01).
      In a multivariate model, only stage (p=0.013), grade (p<0.0001), and menopausal
      status (p=0.007) retained their prognostic power for predicting disease-free
      survival, and just stage (p<0.0001) and grade (p<0.0001) for predicting overall
      survival. The molecular classification of the tumors almost reached statistical
      significance for predicting overall survival (p=0.06).

PMID- 20032427
TI  - Adenocarcinoma corpus uteri stage I-II: results of a treatment programme based
      upon cytometry.
AB  - The results of a treatment method on adenocarcinoma corpus uteri stage I-II based
      upon cytometrically measured DNA ploidy are presented. All patients had a simple
      hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given
      only to those patients with non-diploid tumours regardless of stage and grade. A
      total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were
      included where 1,396 patients were followed-up for at least 5 years or until
      death and the remaining 238 patients were followed-up 3.5-5 years or until death.
      By using cytometry only, we identified a low-risk group comprising 83% of the
      patients (with 5.2% dead from their disease) and a high-risk group of 17% (with
      15.7% dead from their disease). By using grade only (well- and moderately
      differentiated vs poorly differentiated), the low-risk group comprised 87% of the
      patients (with 4.6% dead from their disease) and the high-risk group 13% (with
      13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic
      and II), the low-risk group comprised 78% of the patients (with 3.6% dead from
      their disease) and the high risk group 22% (with 14.5% dead from their disease).
      By combining these prognostic parameters, we were able to identify small
      subgroups with increased mortality rates in need of adjuvant therapy. As ploidy
      still had a strong prognostic strength regardless of given adjuvant radiotherapy,
      we do not believe that this treatment was effective. We therefore recommend
      future research to be directed toward cytostatics as an alternative adjuvant
      treatment.

PMID- 20032428
TI  - Optical biopsy system distinguishing between hyperplastic and adenomatous polyps
      in the colon during colonoscopy.
AB  - BACKGROUND: It has been established that the removal of adenomatous colon polyps
      drastically reduces the incidence of colorectal cancer (CRC), but polypectomy is
      not without risk. The aim was to determine the correlation between the results of
      an optical biopsy system and the histopathology report of the physical biopsy
      specimens of the same polyps removed at colonoscopy. PATIENTS AND METHODS: Paired
      optical and physical biopsies were performed on 55 polyps with complete
      polypectomy of the same tissue. RESULTS: Fifty-three adenomatous polyps and two
      hyperplastic polyps were identified by the hospital pathologist. The optical
      biopsy system identified 52 polyps as suspect (adenomatous) and 2 as non-suspect
      (hyperplastic). One villous adenoma could not be optically analyzed due to
      friability. CONCLUSION: The WavSTAT Optical Biopsy System provides accurate
      information to the gastroenterologist to assist in distinguishing between
      hyperplastic and adenomatous polyps. It is safe for the patient and does not
      unduly increase the time required for an endoscopic examination.

PMID- 20032429
TI  - Potential pharmacokinetic interactions affecting antitumor drug disposition in
      cancer patients.
AB  - AIM: The extent of potential pharmacokinetic drug-drug interactions affecting
      anticancer agents disposition has not been specifically investigated. The
      prevalence of this type of interaction in adult ambulatory patients receiving
      systemic chemotherapy in our institution was examined. PATIENTS AND METHODS: The
      medication list of 200 consecutive cancer patients receiving intravenous
      chemotherapy was prospectively collected by means of the prescriptions
      (chemotherapy, supportive care, medications for comorbidities) and a
      questionnaire (over-the-counter products). Interacting drugs had to have been
      taken in the previous 7 days. Data concerning the type of cancer and the nature
      of the comorbidities were also collected. Potential pharmacokinetic drug
      interactions affecting the activity of the anticancer agent were identified using
      the guide of drug interactions of the French drug agency (June 2007) and the
      literature. RESULTS: A total of 200 patients (mean age 60 years; range 17-96
      years) entered the study and 73.5% were female. The most common cancer types were
      breast cancer (41%), non-Hodgkin's lymphomas (17.5%), and gastrointestinal tumors
      (12.5%). The majority of the patients (58.5%) had a comorbid illness
      (cardiovascular diseases, hypothyroidism, diabetes, depression). The median
      number of medications per patient was 4 (range 1-14). All the patients received
      systemic chemotherapy but 29 (14.5%) also took anticancer drugs at home. Nine
      potential pharmacokinetic interactions were found in nine patients (frequency:
      4.5%; 95% confidence interval: 1.6-7.4%). Most of the interactions (7/9) involved
      fluconazole that might alter the metabolism of oxazaphosphorines or the
      elimination of bortezomib and paclitaxel. One association was contraindicated.
      Five interactions were not associated with a published clinical effect. No
      interaction with an enzyme or drug transporter inducer (e.g., rifampin, St.
      John's wort) was encountered. CONCLUSION: The frequence of potential
      pharmacokinetic interactions affecting the disposition of antitumor drugs was low
      in this population of ambulatory adult cancer patients and mostly involved the
      antifungal agent fluconazole.

PMID- 20032430
TI  - Superiority of magnetic resonance imaging over conventional radiographs in
      multiple myeloma.
AB  - BACKGROUND: Bone lesions in multiple myeloma (MM) are screened with radiological
      skeletal survey (RSS) due to its widespread availability. Although bone lesions
      can be missed by RSS, more sensitive radiological surveys are not as yet
      recommended for routine use due to the low availability of the methodology and
      economical considerations. CASE REPORT: We report on a 68-year-old male with IgG
      kappa stage IIIA MM presenting with skeletal pain, fatigue and osteolytic
      lesions. Since the patient refrained from more intensive therapy, including
      autologous stem cell transplantation (auto-SCT), he was treated with vertebral
      irradiation and included in an institutionally guided study which randomized
      melphalan, prednisone (MP)-lenalidomide (MPR) to MP alone. Although he initially
      responded, his bone pain reoccurred after three MP cycles. The repeated RSS
      showed minor, if any changes. Therefore, an MRI was added which revealed
      extensive osteolyses and extramedullary disease. Justified by these results it
      was possible to convince the patient that a more intensive therapy approach,
      including auto-SCT, local irradiation and thalidomide maintenance, was
      appropriate. CONCLUSION: This case calls for an earlier integration of MRI and/or
      PET/CT scanning in MM, even if RSS remains unchanged, especially if initial bone
      disease is substantial and/or MM-related symptoms recur. The time course of
      information and linked decision-making point towards the future significance of
      an intensified integration of imaging methodologies in the classification and
      disease management of MM.

PMID- 20032431
TI  - Expression of CXCR4 and its ligand SDF-1 in intestinal-type gastric cancer is
      associated with lymph node and liver metastasis.
AB  - BACKGROUND: Stromal cell-derived factor (SDF)-1 and CXCR4 form an important
      chemokine ligand/receptor pair. Recent studies suggest that CXCR4 is expressed in
      certain cancer cells, and malignant cells use this chemokine/receptor system to
      promote tumor progression and metastasis. However, the pathophysiological
      significance of their expression in gastric cancer tissue has not been fully
      elucidated. PATIENTS AND METHODS: SDF-1 and CXCR4 expression levels in gastric
      cancer specimens obtained from 124 patients were examined by
      immunohistochemistry. RESULTS: The staining intensity of CXCR4 and SDF-1 in
      cancer cells was significantly higher in intestinal-type than in diffuse-type
      gastric cancer. There was a significant correlation between the expression of
      CXCR4 and SDF-1 and liver metastasis and lymphatic metastasis in the intestinal
      type cancer; however, this correlation was not found in the diffuse-type cancer.
      Furthermore, intestinal-type cancer cells that permeated the vascular or
      lymphatic channels as well as liver and lymph node metastases showed strong CXCR4
      and SDF-1 staining. CONCLUSION: The overexpressed CXCR4 and SDF-1 in intestinal
      type cancer cells may be therapeutic targets for preventing lymphatic and
      hematogenous metastasis.

PMID- 20032432
TI  - Gastric metastases originating from breast cancer: report of 8 cases and review
      of the literature.
AB  - BACKGROUND: Breast cancer metastasis to the stomach is rare. It is very important
      to distinguish a breast cancer metastasis to the stomach from a primary gastric
      cancer on the basis of clinical, endoscopic, radiological and histopathological
      features, in order to administer the appropriate treatment. PATIENTS AND METHODS:
      Eight patients with breast cancer metastasis to the stomach were identified in
      our database between 1995 and 2008. The clinicopathological data and outcome from
      the medical records of these patients were then reviewed. RESULTS: The median age
      at initial breast cancer diagnosis was 59.5 years (range 44-75 years), while the
      median interval between the primary breast cancer and the gastric involvement was
      41 months (range 2-82 months). The primary breast cancer histological subtype was
      mostly lobular carcinoma. All the biopsy specimens were estrogen receptor (ER),
      cytokeratin (CK) 7 and gross cystic disease fluid protein-15 (GCDFP-15) positive
      and CK-20 negative, while two of them (25%) were HER-2-neu positive. All the
      patients received chemotherapy and two of them were also treated with hormonal
      treatment. Two patients underwent surgical intervention, while one patient who
      had gastric involvement as the only metastatic site will proceed to surgical
      resection of the stomach. All these three patients were alive after 9, 39 and 44
      months of follow-up, respectively. The response rate to chemotherapy was 50% (1
      complete response [CR], 3 partial responses [PR]), and the median survival was 11
      months (range, 1-44+ months). CONCLUSION: Breast cancer metastasis to the stomach
      can be differentiated from primary gastric cancer by comparing the biopsies from
      the gastric metastasis with the original histological slides from the primary
      breast tumor. Appropriate systemic treatment for metastatic breast carcinoma is
      the preferred treatment, whereas surgical intervention should be reserved for
      palliation or may be indicated in cases of solitary resectable gastrointestinal
      tract metastases.

PMID- 20032433
TI  - Psychosocial risk scale (PRS) for breast cancer in patients with breast disease:
      a prospective case-control study in Kuopio, Finland.
AB  - BACKGROUND: In 1982, Wirsching et al. introduced a psychosocial risk scale (PRS)
      for psychological identification of breast cancer patients before biopsy. To our
      knowledge, the associations between PRS and risk of breast cancer are rarely
      considered together in a prospective study. PATIENTS AND METHODS: This study is
      an extension of the Kuopio Breast Cancer Study. Women with breast symptoms were
      referred by physicians to the Kuopio University Hospital (Finland) and were asked
      to participate in this study. These women (n=115) were interviewed, and all study
      variables were obtained before any diagnostic procedures were carried out, so
      neither the investigator nor the participants knew the final diagnosis of breast
      symptoms at the time of the interview. The research method used was the
      semistructured in-depth interview method. The investigator used the Montgomery
      Asberg depression rating scale (MADRS) to evaluate the depression of the study
      participants. All participants were also asked to complete standardized
      questionnaires (Beck depression inventory and Spielberger trait inventory). The
      investigator estimated the PRS using a 3-point scale: grade I, low psychosocial
      risk; grade II, mild/moderate psychosocial risk; grade III, high psychosocial
      risk for breast cancer. RESULTS: The clinical examination and biopsy showed
      breast cancer in 34 patients, benign breast disease in 53 patients, and 28
      individuals were shown to be healthy (HSS). The results indicated that breast
      cancer patients used more idealization of childhood, and motherhood (p=0.04) than
      did the other groups. PRS was significantly associated with increased breast
      cancer risk (p=0.05). CONCLUSION: The results of this study support a moderate
      association between Wirsching et al.'s PRS score and breast cancer risk. However,
      the biological explanation for such an association is unclear and the exact
      effects of psychological factors on the various hormones relevant to development
      of breast cancer are at present poorly defined.

PMID- 20032434
TI  - Radioimmunotherapy of heavily pre-treated, non-Hodgkin's lymphoma patients:
      efficacy and safety in a routine setting.
AB  - The aim of the present study waw to assess efficacy and safety of radio
      immunotherapy with Zevalin (RIT-Z) in heavily pre-treated, rituximab-refractory
      patients. PATIENTS AND METHODS: We studied 12 patients with indolent lymphoma and
      7 with aggressive lymphoma. The median number of prior rituximab-containing
      treatments was 2; overall, 3 therapies had been previously given. Ten patients
      received RIT-Z as salvage therapy, 9 at high risk of relapse received RIT-Z as
      consolidation. Staging and follow-up were obtained by positron-emission
      tomography. Outcomes assessed were failure-free survival (FFS) and time to next
      treatment (TTNT). RESULTS: Overall FFS and TTNT were 5 and 11 months,
      respectively; median follow-up 13 months. Major findings were i) no long-term
      remissions observed in 7 patients who had not responded to their most recent
      therapy and ii) lack of association between any pre-therapy variables analysed
      and outcomes. Different subgroups showed no difference in terms of toxicity.
      CONCLUSION: We encourage the use of RIT-Z as a consolidation for pre-treated
      patients with both indolent and aggressive lymphoma.

PMID- 20032435
TI  - Wilms' tumor 1 (WT1) peptide immunotherapy for gynecological malignancy.
AB  - BACKGROUND: The object of this study was to investigate the safety and clinical
      response of immunotherapy targeting the WT1 (Wilms' tumor 1) gene product in
      patients with gynecological cancer. PATIENTS AND METHODS: Twelve patients with
      WT1/human leukocyte antigen (HLA)-A*2402-positive gynecological cancer were
      included in a Phase II clinical trial of WT1 vaccine therapy. In all the
      patients, the tumors were resistant to standard therapy. The patients received
      intradermal injections of a HLA-A*2402-restricted, modified 9-mer WT1 peptide
      every week for 12 weeks. Tumor size, which was measured by computed tomography
      (CT), was determined every 4 weeks. The responses were analyzed according to
      Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: The protocol was
      well tolerated; only local erythema occurred at the WT1 vaccine injection site.
      The clinical responses were as follows: stable disease (SD) in 3 patients and
      progressive disease (PD) in 9 patients. No patients had a complete (CR) or
      partial response (PR). The disease control rate was 25.0%. CONCLUSION: Although a
      small, uncontrolled, nonrandomized trial, this study showed that WT1 vaccine
      therapy for patients with gynecological cancer was safe and produced a clinical
      response.

PMID- 20032436
TI  - Relevance of oropharyngeal cancer lymph node metastases in the submandibular
      triangle and the posterior triangle apex.
AB  - BACKGROUND: Neck dissection of levels I and IIB is time consuming and can cause
      several comorbidities. The aim was to analyze whether levels I and IIB need to be
      dissected in patients with oropharyngeal cancer and clinical N0 or N+ neck.
      PATIENTS AND METHODS: A retrospective analysis of 77 patients with oropharyngeal
      cancer was carried out with evaluation of the incidence of neck node metastasis
      in levels I and IIB. RESULTS: None of the patients with cN0 neck had metastases
      in level I or IIB; 12.8% of the patients with cN+ neck had metastases in level I,
      35.1% in level IIA and 25.6% had metastases in level IIB. CONCLUSION: Levels I
      and IIB should be dissected in cN+ neck in order to achieve maximal oncological
      safety. The preservation of levels I and IIB in cN0 neck seems to be justified in
      terms of improving functional results and concomitant reduction of operation
      time.

PMID- 20032437
TI  - Retrospective analysis of concurrent vs. sequential administration of
      radiotherapy and hormone therapy using aromatase inhibitor for hormone receptor
      positive postmenopausal breast cancer.
AB  - BACKGROUND: The optimal sequence of adjuvant aromatase inhibitors and
      postoperative radiotherapy for postoperative patients with hormone receptor
      positive breast cancer treated with breast-conserving surgery is unknown.
      PATIENTS AND METHODS: Retrospective analyses of the association of the treatment
      sequence (concurrent or sequential) of postoperative radiotherapy and adjuvant
      hormone therapy using aromatase inhibitors with breast cancer outcomes such as
      ipsilateral breast tumor recurrence, relapse-free and overall survival, and
      treatment-related complications were performed. Patients were grouped as
      concurrent (aromatase inhibitors given during radiotherapy followed by continued
      aromatase inhibitors; 113 patients) and sequential (radiotherapy followed by
      aromatase inhibitors; 151 patients). RESULTS: At a median follow-up of 2.9 years,
      there were no differences in the breast cancer outcomes and treatment-related
      complications between the two treatment groups. In addition, the frequencies of
      grade 3-5 treatment-related complications were very rare for both treatment
      groups. CONCLUSION: Both concurrent and sequential use of postoperative
      radiotherapy and adjuvant hormone therapy using aromatase inhibitors may be
      allowed in terms of the breast cancer outcomes and treatment-related
      complications.

PMID- 20032438
TI  - Tumour Biology: tumour-associated inflammation versus antitumor immunity.
AB  - The latest research results suggest that tumour-infiltrating leukocytes and the
      intra-tumoural cytokine environment play a central role in both the genesis and
      development of cancer. Over a hundred years ago, Virchow pointed out that
      numerous immune cells occur in the vicinity of practically all malignant tumours
      and that the structure of tumour tissue closely resembles the inflamed region of
      a non-healing wound. With the aid of the latest molecular and cell-biological
      methods, we are not only able today to closely characterise tumour cells and
      their immediate vicinity but also the other cell types present in tumour tissue,
      such as infiltrating immune cells, endothelial cells, connective tissue cells and
      others, both in terms of phenotype and function. In addition, there is growing
      understanding of the significance of the composition and functioning of
      endogenous messenger substances such as cytokines, chemokines and prostaglandins
      in healthy and malignantly altered tissues. From the immunological point of view,
      the main characteristics are dysregulated inflammatory conditions caused by the
      tumour cells themselves or by external factors, depending on the type of tumour
      event. It is evident that prolonged dysregulated inflammatory conditions favour
      not only carcinogenesis but also the local infiltration and metastasis of
      malignantly modified cells and counteract the development of efficient antitumor
      immunity. On the other hand, there are indications that through the polarisation
      of immunological reactions, the ability of immunological regulator and effector
      cells to induce efficient antitumor immunity can be modulated. Within the
      framework of this summary, the essential immunological aspects of tumour
      formation and tumour development known at present are presented and possible new
      therapeutic strategies are discussed.

PMID- 20032439
TI  - MET Is highly expressed in advanced stages of colorectal cancer and indicates
      worse prognosis and mortality.
AB  - The aim of the present study was to evaluate by immunohistochemistry the
      prognostic meaning of the tumor marker MET (hepatocyte growth factor) in patients
      submitted to surgical resection due to primary colorectal adenocarcinoma.
      PATIENTS AND METHODS: A retrospective study was carried out that included 286
      consecutive patients with colorectal adenocarcinoma, submitted to surgical
      resection at Barretos Cancer Hospital, from 1993 to 2002. The histopathological
      expression of the MET tumor marker was evaluated using an anti-protein monoclonal
      antibody against MET by the streptavidin-biotin-peroxidase technique. The
      expression of the tumor marker was semi-quantitative, and the slide samples were
      independently analyzed by three pathologists unaware of patient clinical and
      histopathological data. RESULTS: The tumor marker expression was positive in 236
      (79%) out of a total of 286 patients. This expression was statistically
      significantly different between stages I and IV (p=0.004), for overall survival
      (p=0.009), and for cancer-related mortality rates (p=0.022). However, no
      association between the tumor marker and recurrence (p=0.89) or disease-free
      interval (p=0.91) was observed. CONCLUSION: MET has shown significant expression
      at advanced stages of the disease, as well as for overall survival and cancer
      related mortality rates demonstrating to be a valuable marker for poor prognosis
      in colorectal cancer patients.

PMID- 20032440
TI  - Serum homocysteine, cholesterol, retinol, alpha-tocopherol, glycosylated
      hemoglobin and inflammatory response during therapy with bevacizumab,
      oxaliplatin, 5-fluorouracil and leucovorin.
AB  - BACKGROUND: Targeted agents present with a new spectrum of side-effects,
      including toxicities that negatively impact the risk of atherosclerosis. The aim
      of the present study was to evaluate the effect of the combination of targeted
      therapy and chemotherapy on serum homocysteine and other laboratory parameters of
      cardiovascular risk in patients with metastatic colorectal carcinoma. PATIENTS
      AND METHODS: Thirty-one patients with metastatic colorectal carcinoma treated
      with the combination of bevacizumab, oxaliplatin, 5-fluorouracil and leucovorin
      were studied before and during the therapy. RESULTS: Serum homocysteine decreased
      significantly throughout the course of treatment. Total cholesterol and low
      density lipoprotein cholesterol also decreased significantly during the first
      month of therapy. In contrast, serum retinol significantly increased during the
      second and third months of treatment. A significant increase in glycosylated
      hemoglobin was also observed. After an initial rise, serum C-reactive protein
      (CRP) and carcinoembryonic antigen (CEA) were significantly lower compared to
      baseline throughout the course of treatment. Serum ferritin increased throughout
      most of the course of treatment. A significant correlation was observed between
      CRP and high-density lipoprotein cholesterol, retinol, ferritin, and CEA. CEA
      correlated with hemoglobin, retinol, and ferritin. Retinol correlated
      significantly with hemoglobin. CONCLUSION: Tumor control, reflected in lower CEA,
      resulted in suppression of the acute phase response and generally in favorable
      effects on laboratory parameters indicative of risk factors of atherosclerosis,
      including lower homocysteine concentrations, and lower total and LDL cholesterol.

PMID- 20032441
TI  - Determinants of small bowel toxicity in postoperative pelvic irradiation for
      gynaecological malignancies.
AB  - BACKGROUND: Patients treated with postoperative radiotherapy for endometrial and
      cervical carcinomas from 1981 to 2000 were retrospectively analysed in order to
      assess the rate of late small bowel toxicity. PATIENTS AND METHODS: Eight hundred
      and six patients had received pelvic irradiation, with total doses of 40-55 Gy.
      The mean age was 57 years. Three hundred and eighteen patients had been treated
      for cervical and 488 for endometrial cancer; 46 had diabetes and 22 vascular
      diseases; 141 had a history of smoking and 367 were previously submitted to
      surgery for benign diseases. A CT treatment plan had been applied in 285
      patients; 256 had been treated by arc moving therapy, 232 with 2 opposed beams
      (AP-PA) and 318 with 3 or 4 coplanar beams. Three hundred and forty-six were
      treated with X photons of 10 MV or more, 202 with 4-5 MV and 258 with cobalt
      gamma rays. Personalized blocks had been used in 389. Thirty-four women had
      received chemotherapy. Five hundred and eighty-four had been treated with dose
      fractions of 180 cGy or more and 56 had received a boost with brachytherapy or
      external beams. Eighty-one had needed treatment discontinuation due to acute
      small bowel toxicity. RESULTS: The median follow-up was 70 months. Thirty five
      patients had bowel obstructions, after a median time of 31 months. The 5- and 10
      year toxicity rates were 4 and 7%. Uni- and multivariate comparisons identified
      age, acute toxicity and dose fraction as predictors for complications.
      CONCLUSION: Postoperative pelvic irradiation with standard techniques for
      gynaecological carcinomas results in tolerable rates of clinically significant
      late bowel damage, while older patients suffering from significant acute toxicity
      seem to be at higher risk.

PMID- 20032442
TI  - The diagnostic and prognostic value of ProGRP in lung cancer.
AB  - AIM: To investigate the diagnostic and prognostic significance of pro-gastrin
      releasing peptide (ProGRP) in non-small cell (NSCLC) and small cell lung cancer
      (SCLC) and compare this marker with other known serum markers in lung cancer.
      PATIENTS AND METHODS: Serum levels of ProGRP, neuron-specific enolase (NSE),
      CYFRA 21-1 and carcinoembryonic antigen (CEA) were measured in 37 patients with
      benign pulmonary disease (BPD), 88 with advanced NSCLC and 37 with SCLC. RESULTS:
      The ProGRP assay showed a better clinical performance than that of NSE in
      discriminating between SCLC and BPD or NSCLC, especially at specificity higher
      than 90%. ProGRP and NSE sensitivity in SCLC at 95% specificity versus the BPD
      group was 78.4% and 48.6%, (p=0.001) and at 97.7% specificity versus NSCLC, 75.7%
      and 37.8%, respectively (p=0.001). A significant association of low ProGRP levels
      with high-grade NSCLC tumors was found (p=0.002). A univariate analysis showed a
      significant association of ProGRP with survival both in NSCLC and SCLC (p=0.03
      and p=0.04, respectively). In multivariate analysis, performance status (PS) and
      CYFRA 21-1 in NSCLC, and PS, CYFRA 21-1 and serum lactic dehydrogenase in SCLC
      were found as significant variables with an independent impact on survival.
      CONCLUSION: ProGRP is a useful marker in SCLC, with diagnostic performance better
      than that of NSE and demonstrating association with survival in NSCLC and SCLC
      limited to univariate analysis.

PMID- 20032443
TI  - Immunohistochemistry of DNA mismatch repair enzyme MSH2 is not correlated with
      prognostic data from endometrial carcinomas.
AB  - BACKGROUND: The human Mut-S-homolog-2 (MSH2) is part of the DNA mismatch repair
      system (MMR). Mutations in genes of the MMR are a predisposition to hereditary
      non-polyposis colorectal cancer (HNPCC). In women, MMR gene mutations may lead to
      primary endometrial cancer (EC). The important function of the MMR for the
      integrity of the DNA during replication makes it probable that the MMR might also
      be involved in the development and the course of sporadic carcinomas.
      Insufficient MMR activity or expression levels could be prognostic markers of the
      disease. PATIENTS AND METHODS: Immunohistochemical analysis of MSH2 was performed
      in 86 tumor samples from patients with EC. RESULTS: Compared to known tumor
      markers, namely estrogen and progesterone receptors, histopathological grading,
      TNM stage and FIGO classification, no significant correlation between MSH2
      immunoreactivity and EC was found. CONCLUSION: MSH2 immunohistochemical analysis
      is not of prognostic value for endometrial carcinoma.

PMID- 20032444
TI  - Circulating tumor cells in solid tumor in metastatic and localized stages.
AB  - The aim of this study was the detection of circulating tumor cells (CTC) in three
      tumor types of epithelial origin. PATIENTS AND METHODS: Four hundred and thirty
      eight patients with breast cancer (56.2% localized and 43.8% metastatic), 195
      with colorectal tumors (84.1% localized and 15.9% metastatic) and 50 with
      prostate cancer (52% localized and 48% metastatic) took part in this study. CTC
      quantification was performed using the CellSpotter Analyzer (Veridex LLC).
      RESULTS: 31.5% of patients with cancer had > or =2 CTCs/7.5 mL but none of the
      healthy volunteers were above this level (p<0.001). Among patients with
      metastatic disease, 62.3% of them had > or =2 CTCs/7.5 mL but only 14.0% of those
      with localized disease were above this level (p<0.001). The presence of CTCs were
      correlated to stage in the three studied tumor types and no differences in the
      number of cells were found between them. CONCLUSION: The presence of more than 2
      CTCs/7.5 ml is a frequent event in metastatic cases. In particular, patients with
      localized disease who have more than 2 CTCs/7.5 ml should be carefully studied to
      determine the possible prognostic and predictive value of this finding.

PMID- 20032445
TI  - Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT.
AB  - The prognosis of patients with glioblastoma is extremely poor despite multimodal
      treatments including surgery, chemotherapy and radiotherapy. Recently, the
      alkylating agent, temozolomide (TMZ) has been shown to improve survival in
      patients with malignant gliomas, including those with glioblastoma in some
      clinical studies, and has become one of the standard modalities for treatment of
      newly diagnosed and recurrent malignant gliomas. The epigenetic silencing of the
      DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) is the
      strongest predictive marker for favorable outcome in patients treated with TMZ.
      However, it remains to be determined how patients with tumors lacking MGMT
      promoter methylation should be treated. Moreover, even patients with TMZ
      sensitive glioblastoma cannot avoid eventual recurrence. In this article, we
      review the mechanism of the effect of TMZ on tumor cells and resistance to TMZ,
      and provide an overview of the current management and trials for patients with
      glioblastoma.

PMID- 20032447
TI  - Mechanism for maintaining homeostasis in the immune system of the intestine.
AB  - Every organism possesses a mechanism for maintaining homeostasis. We have focused
      on the immune system as a system that helps maintain homeostasis of the body, and
      particularly on the intestine as the largest organ of immunity in the body. We
      have also focused our research on the mechanism that responds to foreign
      substances in the intestine, especially the toll-like receptors (TLR). The
      activation of myeloid differentiation primary response gene 88 (MyD88) signal
      transduction as a response to TLR in the intestine is believed to contribute to
      the maintenance of homeostasis of the body through the homeostasis of the
      intestine. Furthermore, significant findings were reported in which signal
      transduction from TLR4 was essential for the maintenance and regulation of the
      intestine. These results strongly suggest the possibility that homeostasis in the
      intestine is maintained by TLR4, and signaling by TLR4 after exposure to
      lipopolysaccharide (LPS) probably has a role in regulating homeostasis. It is
      expected that the prevention and treatment of various diseases using TLR4 will
      continue to develop. As LPS is a substance that enhances the activity of TLR4, it
      will also attract attention as a valuable substance in its own right.

PMID- 20032448
TI  - Intestinal macrophages involved in the homeostasis of the intestine have the
      potential for responding to LPS.
AB  - Recently, there has been interest in the tertiary functions of food, those that
      maintain human health. Moreover, lipopolysaccharides (LPS), which are components
      of Gram-negative bacteria, have been found to be highly effective in activating
      innate immunity and have been rediscovered as new functional food materials. In
      this review, we discuss the significance of LPS as a food component with
      reference to these tertiary functions based on recent findings. There is special
      emphasis on the plasticity of responses to LPS by intestinal macrophages.
      According to the macrophage-network theory, local macrophages cooperate with
      other tissue macrophages. For this reason, this review also discusses the
      possibility that information is transferred throughout the body from intestinal
      macrophages.

PMID- 20032449
TI  - Improvement of allergic dermatitis via regulation of the Th1/Th2 immune system
      balance by macrophages activated with lipopolysaccharide derived from Pantoea
      agglomerans (IP-PA1).
AB  - Recently, the incidence of allergies has been increasing, especially in advanced
      countries. The cause of these allergies is believed to be a failure in the immune
      system balance that has been caused by changes in the living environment. The
      incidence of allergy shows a negative correlation with the decrease of infectious
      diseases in childhood. It has been suggested that the key to alleviating
      allergies is to activate innate immunity by exposure to microbial components such
      as lipopolysaccharides (LPS). The activation of innate immunity is expected to
      normalize the T-helper type 1 and 2 (Th1/Th2) immune system balance and to
      suppress the excessive reaction of Th2 type responses that cause immunoglobulin
      (Ig) E-dependent allergies. This study introduces information on how the
      activation of macrophages, which are important in innate immunity, by LPS derived
      from Pantoea agglomerans (IP-PA1) caused suppressive effects on type I allergic
      reactions and improved allergic dermatitis. We also summarize our hypothesis that
      regulating the immune system balance using LPS to stimulate macrophages may be an
      important procedure for preventing and improving allergic dermatitis.

PMID- 20032450
TI  - Comparative immunological analysis of innate immunity activation after oral
      administration of wheat fermented extract to teleost fish.
AB  - BACKGROUND: Intradermal or oral administration of lipopolysaccharide derived from
      Pantoea agglomerans (IP-PA1) has shown prophylactic and antitumor effects without
      serious side-effects. While it is known that tumor necrosis factor (TNF)-alpha
      produced by activated macrophages plays an important role in the expression
      mechanism following intradermal administration, details of the mechanism after
      oral administration remain unclear. In this study, the activation of innate
      immunity using fish as an animal model was investigated. In fish, the innate
      immunity system is dominant over acquired immunity. MATERIALS AND METHODS: Carp
      (Cyprinus carpio L) were fed IP-PA1 for 7 days. Total RNA was extracted from the
      head kidney (a major immune organ of teleost fish), and interleukin (IL) - 1beta,
      IL-6, IL-8, IL-10, IL-12, TNF-alpha and transforming forming growth factor (TGF)
      beta mRNAs were quantified by one-step real-time PCR. Phagocytic and bactericidal
      activity of head kidney leukocytes were estimated using zymosan and Aeromonas
      hydrophila (a pathogenic bacteria), respectively. Serum lysozyme activity was
      assayed with Remazol brilliant Blue stained Micrococcus lysodeikticus. RESULTS:
      Oral administration of IP-PA1 for 7 days augmented the quantity of mRNA
      expression of IL-1beta, IL-8, and TNF-alpha mRNA and reduced the expression level
      of IL-6 mRNA in the head kidney. Phagocytic and bactericidal activity of head
      kidney leukocytes were significantly enhanced. Moreover, serum lysozyme
      activities were significantly augmented. CONCLUSION: The results suggest that
      oral administration of IP-PA1 induced activation of M1 type macrophages in the
      immune organ of fish, and this enhanced the function of pathogen elimination.
      Since the functions of macrophages are highly preserved in comparative
      immunology, there is a high probability that the preventative or curative effect
      on various diseases that have been observed in mammals is also related to the
      activation of macrophages to the M1 type.

PMID- 20032451
TI  - Efficacy of ligand-based targeting for the EGF system in cancer.
AB  - Although drugs inhibiting ErbB receptors such as epidermal growth factor receptor
      (EGFR) and HER2 have been developed as anticancer agents targeting the EGF
      family, they are not effective for all types of cancer and instead target only
      certain types. We propose the following four main reasons for these observations:
      (i) although seven EGFR ligands exist, effective inhibition of specific EGFR
      ligands may occur because their expression levels differ in different
      malignancies; (ii) suppressing EGFR ligands inhibits aggregation of EGFR and
      other ErbB receptors and activation of ERK and Akt signals; (iii) EGFR ligands
      may have various combinations for signal transduction through the EGFR pathway
      and other receptor signals; and (iv) the intracellular C-terminals of EGFR
      ligands move into the nucleus and strongly regulate cell proliferation. In this
      review, we describe important implications for targeted cancer therapy against
      EGFR ligands and describe the current situation in the development of ligand
      based therapies for cancer.

PMID- 20032452
TI  - Correlation between WT1 expression and cell proliferation in endometrial cancer.
AB  - BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in endometrial cancer.
      Although recent studies have revealed that WT1 is a new prognostic factor, it
      remains unclear whether WT1 plays a pathophysiological role including cell
      proliferation. PATIENTS AND METHODS: A series of 70 endometrial cancer patients
      who had undergone a curative resection was studied by immunohistochemistry to
      determine the correlation between WT1 expression and cell proliferation
      (proliferating cell nuclear antigen; PCNA). RESULTS: WT1 expression was observed
      in 64 cases (91%). WT1 expression was associated with advanced FIGO stage
      (p=0.0228), myometrial invasion (p=0.0114) and high-grade histological
      differentiation (p=0.0004), indicating up-regulation of WT1 expression with tumor
      progression. A positive correlation between PCNA labeling index and score of WT1
      expression was observed (p=0.0081, rho=0.319). CONCLUSION: These results showed
      that WT1 might regulate cell proliferation in endometrial cancer.

PMID- 20032453
TI  - A study of the postoperative course in cases of GIST of the stomach. The efficacy
      of imatinib in cases of recurrence.
AB  - BACKGROUND: The postoperative course of cases of gastrointestinal stromal tumor
      (GIST) of the stomach was studied in patients who underwent surgery in this
      Department. In addition, treatment with the molecular-targeted drug imatinib was
      studied in cases of recurrence. PATIENTS AND METHODS: We studied 40 cases with a
      diagnosis of GIST of the stomach where the patient subsequently underwent surgery
      in this Department between July 1985 (when this facility opened) and December
      2007. Six of these cases involved patients with carcinoma or carcinoid tumors,
      which could have affected the procedure and prognosis, and 2 cases involved
      patients who developed cancer during the postoperative course of the GIST.
      Therefore these 8 patients were excluded, thus resulting in the study of a total
      of 32 patients. RESULTS: The male:female ratio for the 32 patients was 17:15, the
      average tumor size was 4.7+/-3.4 cm (with a range of 1.3-16.0 cm), and the median
      follow-up was 92.2+/-73.7 months (with a range of 2-238 months). Recurrence
      occurred in 6 out of the 32 patients (18.8%) and was observed in the liver of 5
      patients, in the lungs of 2 patients, in the peritoneum of 2 patients, locally in
      1 patient, and in the bone of 1 patient (including patients with multiple sites).
      With respect to the tumor size, the incidence of recurrence of tumors smaller
      than 2 cm was 0%, 16.7% for patients with tumors 2 to 5 cm in size, and 27.3% for
      these with tumors larger than 5 cm. The incidence of recurrence was particularly
      marked in patients with tumors larger than 10 cm (66.7%). The treatment for
      recurrence was transcatheter arterial embolization for 1 patient and imatinib for
      5 patients. In cases where imatinib was administered, 1 patient exhibited partial
      response, 1 patient exhibited stable disease, and 3 patients exhibited
      progressive disease, indicating a response rate of 20%. Postoperative recurrence
      of GIST of the stomach in this study occurred in 6 of 32 patients (18.8%). The
      incidence of recurrence of tumors larger than 10 cm was 2 out of 3 patients.
      CONCLUSION: In cases of recurrence, the response rate to imatinib was 20%.
      Imatinib was effective against GIST that were positive for KIT protein, but
      future study is needed to clarify the risk factors for recurrence and indications
      for adjuvant therapy in cases of GIST.

PMID- 20032454
TI  - Role of C-terminal region of yeast ADP/ATP carrier 2 protein: dynamics of
      flexible C-terminal arm.
AB  - BACKGROUND: The ADP/ATP carrier catalyzes the exchange of ADP and ATP across the
      inner mitochondrial membrane. MATERIALS AND METHODS: The molecular dynamics of
      modeled yeast type 2 AAC (yAAC2) was analyzed and molecular parameters were
      determined. RESULTS: The yAAC2 C-terminal moved flexibly and a negative
      electrostatic potential field (ESP) was located in the C-terminal region. The ESP
      field is always located in the C-terminal area during C-terminal truncation (d1
      d9). Further C-terminal truncation occurred on field invagination into the core
      region (d11, d14, d16). The 2-6 C-terminal amino acid truncation did not affect
      the biological activity. The d7-d9 truncated mutants lost their biological
      function. CONCLUSION: A critical point in yAAC2 function was shown between d6 and
      d7 C-terminal truncation. The C-terminal structure of yAAC2 is thought to be
      involved in biological function control.

PMID- 20032455
TI  - Why does religiosity persist?

PMID- 20032456
TI  - Characterization and functional restoration of a potassium channel Kir6.2 pore
      mutation identified in congenital hyperinsulinism.
AB  - The inwardly rectifying potassium channel Kir6.2 assembles with sulfonylurea
      receptor 1 to form the ATP-sensitive potassium (K(ATP)) channels that regulate
      insulin secretion in pancreatic beta-cells. Mutations in K(ATP) channels underlie
      insulin secretion disease. Here, we report the characterization of a heterozygous
      missense Kir6.2 mutation, G156R, identified in congenital hyperinsulinism.
      Homomeric mutant channels reconstituted in COS cells show similar surface
      expression as wild-type channels but fail to conduct potassium currents. The
      mutated glycine is in the pore-lining transmembrane helix of Kir6.2; an
      equivalent glycine in other potassium channels has been proposed to serve as a
      hinge to allow helix bending during gating. We found that mutation of an adjacent
      asparagine, Asn-160, to aspartate, which converts the channel from a weak to a
      strong inward rectifier, on the G156R background restored ion conduction in the
      mutant channel. Unlike N160D channels, however, G156R/N160D channels are not
      blocked by intracellular polyamines at positive membrane potential and exhibit
      wild-type-like nucleotide sensitivities, suggesting the aspartate introduced at
      position 160 interacts with arginine at 156 to restore ion conduction and gating.
      Using tandem Kir6.2 tetramers containing G156R and/or N160D in designated
      positions, we show that one mutant subunit in the tetramer is insufficient to
      abolish conductance and that G156R and N160D can interact in the same or adjacent
      subunits to restore conduction. We conclude that the glycine at 156 is not
      essential for K(ATP) channel gating and that the Kir6.2 gating defect caused by
      the G156R mutation could be rescued by manipulating chemical interactions between
      pore residues.

PMID- 20032457
TI  - Specificity of the BRISC deubiquitinating enzyme is not due to selective binding
      to Lys63-linked polyubiquitin.
AB  - BRISC (Brcc36-containing isopeptidase complex) is a four-subunit deubiquitinating
      (DUB) enzyme that has a catalytic subunit, called Brcc36, that is a member of the
      JAMM/MPN(+) family of zinc metalloproteases. A notable feature of BRISC is its
      high specificity for cleaving Lys(63)-linked polyubiquitin. Here, we show that
      BRISC selectivity is not due to preferential binding to Lys(63)-linked
      polyubiquitin but is instead dictated by how the substrate isopeptide linkage is
      oriented within the enzyme active site. BRISC possesses a high affinity binding
      site for the ubiquitin hydrophobic surface patch that accounts for the bulk of
      the affinity between enzyme and substrate. Although BRISC can interact with
      either subunit of a diubiquitin conjugate, substrate cleavage occurs only when
      BRISC is bound to the hydrophobic patch of the distal (i.e. the "S1") ubiquitin
      at a ubiquitin-ubiquitin cleavage site. The importance of the Lys(63)-linked
      proximal (S1') ubiquitin was underscored by our finding that BRISC could not
      cleave the isopeptide bond joining a ubiquitin to a non-ubiquitin substrate.
      Finally, we also show that Abro1, another BRISC subunit, binds directly to Brcc36
      and that the Brcc36-Abro1 heterodimer includes a minimal complex with Lys(63)
      specific DUB activity.

PMID- 20032458
TI  - The structure of the trimer of human 4-1BB ligand is unique among members of the
      tumor necrosis factor superfamily.
AB  - Binding of the 4-1BB ligand (4-1BBL) to its receptor, 4-1BB, provides the T
      lymphocyte with co-stimulatory signals for survival, proliferation, and
      differentiation. Importantly, the 4-1BB-4-1BBL pathway is a well known target for
      anti-cancer immunotherapy. Here we present the 2.3-A crystal structure of the
      extracellular domain of human 4-1BBL. The ectodomain forms a homotrimer with an
      extended, three-bladed propeller structure that differs from trimers formed by
      other members of the tumor necrosis factor (TNF) superfamily. Based on the 4-1BBL
      structure, we modeled its complex with 4-1BB, which was consistent with images
      obtained by electron microscopy, and verified the binding site by site-directed
      mutagenesis. This structural information will facilitate the development of
      immunotherapeutics targeting 4-1BB.

PMID- 20032459
TI  - Interactions between copper-binding sites determine the redox status and
      conformation of the regulatory N-terminal domain of ATP7B.
AB  - Copper-transporting ATPase ATP7B is essential for human copper homeostasis and
      normal liver function. ATP7B has six N-terminal metal-binding domains (MBDs) that
      sense cytosolic copper levels and regulate ATP7B. The mechanism of copper sensing
      and signal integration from multiple MBDs is poorly understood. We show that MBDs
      communicate and that this communication determines the oxidation state and
      conformation of the entire N-terminal domain of ATP7B (N-ATP7B). Mutations of
      copper-coordinating Cys to Ala in any MBD (2, 3, 4, or 6) change the N-ATP7B
      conformation and have distinct functional consequences. Mutating MBD2 or MBD3
      causes Cys oxidation in other MBDs and loss of copper binding. In contrast,
      mutation of MBD4 and MBD6 does not alter the redox status and function of other
      sites. Our results suggest that MBD2 and MBD3 work together to regulate access to
      other metal-binding sites, whereas MBD4 and MBD6 receive copper independently,
      downstream of MBD2 and MBD3. Unlike Ala substitutions, the Cys-to-Ser mutation in
      MBD2 preserves the conformation and reduced state of N-ATP7B, suggesting that
      hydrogen bonds contribute to interdomain communications. Tight coupling between
      MBDs suggests a mechanism by which small changes in individual sites (induced by
      copper binding or mutation) result in stabilization of distinct conformations of
      the entire N-ATP7B and altered exposure of sites for interactions with regulatory
      proteins.

PMID- 20032460
TI  - Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced
      synaptic disruption.
AB  - Synaptic degeneration, including impairment of synaptic plasticity and loss of
      synapses, is an important feature of Alzheimer disease pathogenesis. Increasing
      evidence suggests that these degenerative synaptic changes are associated with an
      accumulation of soluble oligomeric assemblies of amyloid beta (Abeta) known as
      ADDLs. In primary hippocampal cultures ADDLs bind to a subpopulation of neurons.
      However the molecular basis of this cell type-selective interaction is not
      understood. Here, using siRNA screening technology, we identified alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits and
      calcineurin as candidate genes potentially involved in ADDL-neuron interactions.
      Immunocolocalization experiments confirmed that ADDL binding occurs in dendritic
      spines that express surface AMPA receptors, particularly the calcium-impermeable
      type II AMPA receptor subunit (GluR2). Pharmacological removal of the surface
      AMPA receptors or inhibition of AMPA receptors with antagonists reduces ADDL
      binding. Furthermore, using co-immunoprecipitation and photoreactive amino acid
      cross-linking, we found that ADDLs interact preferentially with GluR2-containing
      complexes. We demonstrate that calcineurin mediates an endocytotic process that
      is responsible for the rapid internalization of bound ADDLs along with surface
      AMPA receptor subunits, which then both colocalize with cpg2, a molecule
      localized specifically at the postsynaptic endocytic zone of excitatory synapses
      that plays an important role in activity-dependent glutamate receptor
      endocytosis. Both AMPA receptor and calcineurin inhibitors prevent oligomer
      induced surface AMPAR and spine loss. These results support a model of disease
      pathogenesis in which Abeta oligomers interact selectively with neurotransmission
      pathways at excitatory synapses, resulting in synaptic loss via facilitated
      endocytosis. Validation of this model in human disease would identify therapeutic
      targets for Alzheimer disease.

PMID- 20032461
TI  - Control of steroid 21-oic acid synthesis by peroxisome proliferator-activated
      receptor alpha and role of the hypothalamic-pituitary-adrenal axis.
AB  - A previous study identified the peroxisome proliferator-activated receptor alpha
      (PPARalpha) activation biomarkers 21-steroid carboxylic acids 11beta-hydroxy-3,20
      dioxopregn-4-en-21-oic acid (HDOPA) and 11beta,20-dihydroxy-3-oxo-pregn-4-en-21
      oic acid (DHOPA). In the present study, the molecular mechanism and the metabolic
      pathway of their production were determined. The PPARalpha-specific time
      dependent increases in HDOPA and 20alpha-DHOPA paralleled the development of
      adrenal cortex hyperplasia, hypercortisolism, and spleen atrophy, which was
      attenuated in adrenalectomized mice. Wy-14,643 activation of PPARalpha induced
      hepatic FGF21, which caused increased neuropeptide Y and agouti-related protein
      mRNAs in the hypothalamus, stimulation of the agouti-related protein/neuropeptide
      Y neurons, and activation of the hypothalamic-pituitary-adrenal (HPA) axis,
      resulting in increased adrenal cortex hyperplasia and corticosterone production,
      revealing a link between PPARalpha and the HPA axis in controlling energy
      homeostasis and immune regulation. Corticosterone was demonstrated as the
      precursor of 21-carboxylic acids both in vivo and in vitro. Under PPARalpha
      activation, the classic reductive metabolic pathway of corticosterone was
      suppressed, whereas an alternative oxidative pathway was uncovered that leads to
      the sequential oxidation on carbon 21 resulting in HDOPA. The latter was then
      reduced to the end product 20alpha-DHOPA. Hepatic cytochromes P450, aldehyde
      dehydrogenase (ALDH3A2), and 21-hydroxysteroid dehydrogenase (AKR1C18) were found
      to be involved in this pathway. Activation of PPARalpha resulted in the induction
      of Aldh3a2 and Akr1c18, both of which were confirmed as target genes through
      introduction of promoter luciferase reporter constructs into mouse livers in
      vivo. This study underscores the power of mass spectrometry-based metabolomics
      combined with genomic and physiologic analyses in identifying downstream
      metabolic biomarkers and the corresponding upstream molecular mechanisms.

PMID- 20032462
TI  - Effect of lipid particle biogenesis on the subcellular distribution of squalene
      in the yeast Saccharomyces cerevisiae.
AB  - Squalene belongs to the group of isoprenoids and is a precursor for the synthesis
      of sterols, steroids, and ubiquinones. In the yeast Saccharomyces cerevisiae, the
      amount of squalene can be increased by variation of growth conditions or by
      genetic manipulation. In this report, we show that a hem1Delta mutant accumulated
      a large amount of squalene, which was stored almost exclusively in cytoplasmic
      lipid particles/droplets. Interestingly, a strain bearing a hem1Delta deletion in
      a dga1Delta lro1Delta are1Delta are2Delta quadruple mutant background
      (QMhem1Delta), which is devoid of the classical storage lipids, triacylglycerols
      and steryl esters, and lacks lipid particles, accumulated squalene at similar
      amounts as the hem1Delta mutant in a wild type background. In QMhem1Delta,
      however, increased amounts of squalene were found in cellular membranes,
      especially in microsomes. The fact that QMhem1Delta did not form lipid particles
      indicated that accumulation of squalene solely was not sufficient to initiate
      proliferation of lipid particles. Most importantly, these results also
      demonstrated that (i) squalene was not lipotoxic under the conditions tested, and
      (ii) organelle membranes in yeast can accommodate relatively large quantities of
      this non-polar lipid without compromising cellular functions. In summary,
      localization of squalene as described here can be regarded as an unconventional
      example of non-polar lipid storage in cellular membranes.

PMID- 20032463
TI  - Histone deacetylase 10 relieves repression on the melanogenic program by
      maintaining the deacetylation status of repressors.
AB  - HDAC10 belongs to the class II histone deacetylase family; however, its functions
      remain enigmatic. We report here that the HDAC10 protein complex contained
      deacetylated chaperone protein hsc70, and HDAC10 relieved repression of
      melanogenesis by decreasing the repressional activity of two transcriptional
      regulators, paired box protein 3 (Pax3) and KRAB-associated protein 1 (KAP1).
      HDAC10 physically interacted with Pax3 and KAP1 in a ternary complex and
      maintained Pax3 and KAP1 in a deacetylated state. Deacetylated Pax3 and KAP1
      derepressed promoters of microphthalmia-associated transcription factor (MITF)
      and melanocyte-specific tyrosinase-related protein 1 and 2 (TRP-1 and TRP-2),
      three genes of the melanogenesis cascade, in a trichostatin A-sensitive manner.
      Co-occupancy of melanogenic promoters by HDAC10, Pax3, and KAP1 only happened in
      cells of the melanocyte lineage, and KAP1 facilitated nuclear enrichment of
      HDAC10. Finally, cellular melanin content correlated directly with the expression
      level and activity of HDAC10. Our results not only show that HDAC10 regulates
      melanogenesis but also demonstrate that the transcriptional activities of Pax3
      and KAP1 are intimately linked to their acetylation status.

PMID- 20032464
TI  - Proteome of acidic phospholipid-binding proteins: spatial and temporal regulation
      of Coronin 1A by phosphoinositides.
AB  - Reversible interactions between acidic phospholipids in the cellular membrane and
      proteins in the cytosol play fundamental roles in a wide variety of physiological
      events. Here, we present a novel approach to the identification of acidic
      phospholipid-binding proteins using nano-liquid chromatography-tandem mass
      spectrometry. We found more than 400 proteins, including proteins with previously
      known acidic phospholipid-binding properties, and confirmed that several
      candidates, such as Coronin 1A, mDia1 (Diaphanous-related formin-1),
      PIR121/CYFIP2, EB2 (end plus binding protein-2), KIF21A (kinesin family member
      21A), eEF1A1 (translation elongation factor 1alpha1), and TRIM2, directly bind to
      acidic phospholipids. Among such novel proteins, we provide evidence that Coronin
      1A activity, which disassembles Arp2/3-containing actin filament branches, is
      spatially and temporally regulated by phosphatidylinositol 4,5-bisphosphate
      (PI(4,5)P(2)). Whereas Coronin 1A co-localizes with PI(4,5)P(2) at the plasma
      membrane in resting cells, it is dissociated from the plasma membrane during
      lamellipodia formation where the PI(4,5)P(2) signal is significantly reduced. Our
      in vitro experiments show that Coronin 1A preferentially binds to PI(4,5)P(2)
      containing liposomes and that PI(4,5)P(2) antagonizes the ability of Coronin 1A
      to disassemble actin filament branches, indicating a spatiotemporal regulation of
      Coronin 1A via a direct interaction with the plasma membrane lipid. Collectively,
      our proteomics data provide a list of potential acidic phospholipid-binding
      protein candidates ranging from the actin regulatory proteins to translational
      regulators.

PMID- 20032465
TI  - Down-regulation of S1P1 receptor surface expression by protein kinase C
      inhibition.
AB  - The sphingosine 1-phosphate receptor type 1 (S1P(1)) is important for the
      maintenance of lymphocyte circulation. S1P(1) receptor surface expression on
      lymphocytes is critical for their egress from thymus and lymph nodes. Premature
      activation-induced internalization of the S1P(1) receptor in lymphoid organs,
      mediated either by pharmacological agonists or by inhibition of the S1P degrading
      enzyme S1P-lyase, blocks lymphocyte egress and induces lymphopenia in blood and
      lymph. Regulation of S1P(1) receptor surface expression is therefore a promising
      way to control adaptive immunity. Hence, we analyzed potential cellular targets
      for their ability to alter S1P(1) receptor surface expression without
      stimulation. The initial observation that preincubation of mouse splenocytes with
      its natural analog sphingosine was sufficient to block Transwell chemotaxis to
      S1P directed subsequent investigations to the underlying mechanism. Sphingosine
      is known to inhibit protein kinase C (PKC), and PKC inhibition with nanomolar
      concentrations of staurosporine, calphostin C, and GF109203X down-regulated
      surface expression of S1P(1) but not S1P(4) in transfected rat hepatoma HTC(4)
      cells. The PKC activator phorbol 12-myristate 13-acetate partially rescued FTY720
      induced down-regulation of the S1P(1) receptor, linking PKC activation with
      S1P(1) receptor surface expression. FTY720, but not FTY720 phosphate, efficiently
      inhibited PKC. Cell-based efficacy was obvious with 10 nm FTY720, and in vivo
      treatment of mice with 0.3-3 mg/kg/day FTY720 showed increasing concentration
      dependent effectiveness. PKC inhibition therefore may contribute to lymphopenia
      by down-regulating S1P(1) receptor cell surface expression independently from its
      activation.

PMID- 20032466
TI  - Electron transport chain-dependent and -independent mechanisms of mitochondrial
      H2O2 emission during long-chain fatty acid oxidation.
AB  - Oxidative stress in skeletal muscle is a hallmark of various pathophysiologic
      states that also feature increased reliance on long-chain fatty acid (LCFA)
      substrate, such as insulin resistance and exercise. However, little is known
      about the mechanistic basis of the LCFA-induced reactive oxygen species (ROS)
      burden in intact mitochondria, and elucidation of this mechanistic basis was the
      goal of this study. Specific aims were to determine the extent to which LCFA
      catabolism is associated with ROS production and to gain mechanistic insights
      into the associated ROS production. Because intermediates and by-products of LCFA
      catabolism may interfere with antioxidant mechanisms, we predicted that ROS
      formation during LCFA catabolism reflects a complex process involving multiple
      sites of ROS production as well as modified mitochondrial function. Thus, we
      utilized several complementary approaches to probe the underlying mechanism(s).
      Using skeletal muscle mitochondria, our findings indicate that even a low supply
      of LCFA is associated with ROS formation in excess of that generated by NADH
      linked substrates. Moreover, ROS production was evident across the physiologic
      range of membrane potential and was relatively insensitive to membrane potential
      changes. Determinations of topology and membrane potential as well as use of
      inhibitors revealed complex III and the electron transfer flavoprotein (ETF) and
      ETF-oxidoreductase, as likely sites of ROS production. Finally, ROS production
      was sensitive to matrix levels of LCFA catabolic intermediates, indicating that
      mitochondrial export of LCFA catabolic intermediates can play a role in
      determining ROS levels.

PMID- 20032467
TI  - Carbohydrate recognition properties of human ficolins: glycan array screening
      reveals the sialic acid binding specificity of M-ficolin.
AB  - Ficolins are oligomeric innate immune recognition proteins consisting of a
      collagen-like region and a fibrinogen-like recognition domain that bind to
      pathogen- and apoptotic cell-associated molecular patterns. To investigate their
      carbohydrate binding specificities, serum-derived L-ficolin and recombinant H-
      and M-ficolins were fluorescently labeled, and their carbohydrate binding ability
      was analyzed by glycan array screening. L-ficolin preferentially recognized
      disulfated N-acetyllactosamine and tri- and tetrasaccharides containing terminal
      galactose or N-acetylglucosamine. Binding was sensitive to the position and
      orientation of the bond between N-acetyllactosamine and the adjacent
      carbohydrate. No significant binding of H-ficolin to any of the 377 glycans
      probed could be detected, providing further evidence for its poor lectin
      activity. M-ficolin bound preferentially to 9-O-acetylated 2-6-linked sialic acid
      derivatives and to various glycans containing sialic acid engaged in a 2-3
      linkage. To further investigate the structural basis of sialic acid recognition
      by M-ficolin, point mutants were produced in which three residues of the
      fibrinogen domain were replaced by their counterparts in L-ficolin. Mutations
      G221F and A256V inhibited binding to the 9-O-acetylated sialic acid derivatives,
      whereas Y271F abolished interaction with all sialic acid-containing glycans. The
      crystal structure of the Y271F mutant fibrinogen domain was solved, showing that
      the mutation does not alter the structure of the ligand binding pocket. These
      analyses reveal novel ficolin ligands such as sulfated N-acetyllactosamine (L
      ficolin) and gangliosides (M-ficolin) and provide precise insights into the
      sialic acid binding specificity of M-ficolin, emphasizing the essential role of
      Tyr(271) in this respect.

PMID- 20032468
TI  - Spontaneous development of endoplasmic reticulum stress that can lead to diabetes
      mellitus is associated with higher calcium-independent phospholipase A2
      expression: a role for regulation by SREBP-1.
AB  - Our recent studies indicate that endoplasmic reticulum (ER) stress causes INS-1
      cell apoptosis by a Ca(2+)-independent phospholipase A(2) (iPLA(2)beta)-mediated
      mechanism that promotes ceramide generation via sphingomyelin hydrolysis and
      subsequent activation of the intrinsic pathway. To elucidate the association
      between iPLA(2)beta and ER stress, we compared beta-cell lines generated from
      wild type (WT) and Akita mice. The Akita mouse is a spontaneous model of ER
      stress that develops hyperglycemia/diabetes due to ER stress-induced beta-cell
      apoptosis. Consistent with a predisposition to developing ER stress, basal
      phosphorylated PERK and activated caspase-3 are higher in the Akita cells than WT
      cells. Interestingly, basal iPLA(2)beta, mature SREBP-1 (mSREBP-1),
      phosphorylated Akt, and neutral sphingomyelinase (NSMase) are higher, relative
      abundances of sphingomyelins are lower, and mitochondrial membrane potential
      (DeltaPsi) is compromised in Akita cells, in comparison with WT cells. Exposure
      to thapsigargin accelerates DeltaPsi loss and apoptosis of Akita cells and is
      associated with increases in iPLA(2)beta, mSREBP-1, and NSMase in both WT and
      Akita cells. Transfection of Akita cells with iPLA(2)beta small interfering RNA,
      however, suppresses NSMase message, DeltaPsi loss, and apoptosis. The iPLA(2)beta
      gene contains a sterol-regulatory element, and transfection with a dominant
      negative SREBP-1 reduces basal mSREBP-1 and iPLA(2)beta in the Akita cells and
      suppresses increases in mSREBP-1 and iPLA(2)beta due to thapsigargin. These
      findings suggest that ER stress leads to generation of mSREBP-1, which can bind
      to the sterol-regulatory element in the iPLA(2)beta gene to promote its
      transcription. Consistent with this, SREBP-1, iPLA(2)beta, and NSMase messages in
      Akita mouse islets are higher than in WT islets.

PMID- 20032469
TI  - Role of WNT-5a in the determination of human mesenchymal stem cells into
      preadipocytes.
AB  - Increasing adipocyte size as well as numbers is important in the development of
      obesity and type 2 diabetes, with adipocytes being generated from mesenchymal
      precursor cells. This process includes the determination of mesenchymal stem
      cells (MSC) into preadipocytes (PA) and the differentiation of PA into mature fat
      cells. Although the process of differentiation has been highly investigated, the
      determination in humans is poorly understood. In this study, we compared human
      MSC and human committed PA on a cellular and molecular level to gain further
      insights into the regulatory mechanisms in the determination process. Both cell
      types showed similar morphology and expression patterns of common mesenchymal and
      hematopoietic surface markers. However, although MSC were able to differentiate
      into adipocytes and osteocytes, PA were only able to undergo adipogenesis,
      indicating that PA lost their multipotency during determination. WNT-5a
      expression showed significantly higher levels in MSC compared with PA suggesting
      that WNT-5a down-regulation might be important in the determination process.
      Indeed, incubation of human MSC in medium containing neutralizing WNT-5a
      antibodies abolished their ability to undergo osteogenesis, although adipogenesis
      was still possible. An opposite effect was achieved using recombinant WNT-5a
      protein. On a molecular level, WNT-5a was found to promote c-Jun N-terminal
      kinase-dependent intracellular signaling in MSC. Activation of this noncanonical
      pathway resulted in the induction of osteopontin expression further indicating
      pro-osteogenic effects of WNT-5a. Our data suggest that WNT-5a is necessary to
      maintain osteogenic potential of MSC and that inhibition of WNT-5a signaling
      therefore plays a role in their determination into PA in humans.

PMID- 20032470
TI  - De novo lipogenesis and stearoyl-CoA desaturase are coordinately regulated in the
      human adipocyte and protect against palmitate-induced cell injury.
AB  - De novo lipogenesis (DNL) is paradoxically up-regulated by its end product,
      saturated fatty acids (SAFAs). We tested the hypothesis that SAFA-induced up
      regulation of DNL reflects coordinate up-regulation of elongation and
      desaturation pathways for disposal of SAFAs and production of monounsaturated
      fatty acids to protect cells from SAFA toxicity. Human preadipocytes were
      differentiated in vitro for 14 days with [U-(13)C]palmitate (0-200 microM) to
      distinguish exogenous fatty acids from those synthesized by DNL. Exogenous
      palmitate up-regulated DNL (p < 0.001) concomitantly with SCD and elongation
      (each p < 0.001). Adipocytes from some donors were intolerant to high palmitate
      concentrations (400 microM). Palmitate-intolerant cells showed lower TG
      accumulation. They had lower expression of SCD mRNA and less monounsaturated
      fatty acids in TG, emphasizing the importance of desaturation for dealing with
      exogenous SAFAs. There was greater [U-(13)C]palmitate incorporation in
      phospholipids. SCD knockdown with small interfering RNA caused down-regulation of
      DNL and of expression of DNL-related genes, with reduced membrane fluidity (p <
      0.02) and insulin sensitivity (p < 0.01), compared with scrambled small
      interfering RNA controls. There was preferential channeling of DNL-derived versus
      exogenous palmitate into elongation and of DNL-derived versus exogenous stearate
      into desaturation. DNL may not act primarily to increase fat stores but may serve
      as a key regulator, in tandem with elongation and desaturation, to maintain cell
      membrane fluidity and insulin sensitivity within the human adipocyte.

PMID- 20032472
TI  - INCAP Oriente longitudinal study: 40 years of history and legacy.
AB  - Our purpose in this article is to describe the objectives, design, overall
      coverage, and main domains of data collection of the Institute of Nutrition of
      Central America and Panama Oriente Longitudinal Study and subsequent follow-up
      studies. This supplementary feeding trial targeted to pregnant and lactating
      women and children from birth to 7 y of age, conducted in 4 rural Guatemalan
      villages (1969-77) with a series of follow-up studies (1988-2007), is one of the
      richest sources of information on the effects of nutrition, growth, development,
      and human capital in the developing world, with outstanding data from gestation
      to adult age and 40 y of follow-up. Its results have influenced nutrition
      knowledge and policy with over 300 scientific publications. We present brief
      descriptions of preliminary studies that were critical for the success of the
      trial and the design and methods used during the trial and in the follow-up
      studies, in chronological order.

PMID- 20032471
TI  - Nonsynonymous mutations within APOB in human familial hypobetalipoproteinemia:
      evidence for feedback inhibition of lipogenesis and postendoplasmic reticulum
      degradation of apolipoprotein B.
AB  - Five nontruncating missense APOB mutations, namely A31P, G275S, L324M, G912D, and
      G945S, were identified in heterozygous carriers of familial
      hypobetalipoproteinemia (FHBL) in the Italian population. To test that the FHBL
      phenotype was a result of impaired hepatic secretion of mutant apoB proteins, we
      performed transfection studies using McA-RH7777 cells stably expressing wild type
      or mutant forms of human apolipoprotein B-48 (apoB-48). All mutant proteins
      displayed varied impairment in secretion, with G912D the least affected and A31P
      barely secreted. Although some A31P was degraded by proteasomes, a significant
      proportion of it (although inappropriately glycosylated) escaped endoplasmic
      reticulum (ER) quality control and presented in the Golgi compartment.
      Degradation of the post-ER A31P was achieved by autophagy. Expression of A31P
      also decreased secretion of endogenous apoB and triglycerides, yet the impaired
      lipoprotein secretion did not lead to lipid accumulation in the cells or ER
      stress. Rather, expression of genes involved in lipogenesis was down-regulated,
      including liver X receptor alpha, sterol regulator element-binding protein 1c,
      fatty acid synthase, acetyl-CoA carboxylase 1, stearoyl-CoA desaturase 1, and
      lipin-1. These results suggest that feedback inhibition of hepatic lipogenesis in
      conjunction with post-ER degradation of misfolded apoB proteins can contribute to
      reduce fat accumulation in the FHBL liver.

PMID- 20032473
TI  - The nutrition intervention improved adult human capital and economic
      productivity.
AB  - This article reviews key findings about the long-term impact of a nutrition
      intervention carried out by the Institute of Nutrition of Central America and
      Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04
      show substantial impact on adult human capital and economic productivity. The
      1988-89 study showed that adult body size and work capacity increased for those
      provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed
      that schooling was increased for women and reading comprehension and intelligence
      increased in both men and women. Participants were 26-42 y of age at the time of
      the 2002-04 follow-up, facilitating the assessment of economic productivity.
      Wages of men increased by 46% in those provided with improved nutrition through
      age 2 y. Findings for cardiovascular disease risk factors were heterogeneous;
      however, they suggest that improved nutrition in early life is unlikely to
      increase cardiovascular disease risk later in life and may indeed lower risk. In
      conclusion, the substantial improvement in adult human capital and economic
      productivity resulting from the nutrition intervention provides a powerful
      argument for promoting improvements in nutrition in pregnant women and young
      children.

PMID- 20032474
TI  - The Oriente Study: program and policy impacts.
AB  - This journal supplement summarizes the many contributions of the Oriente Study to
      scientific knowledge. This article asks whether this knowledge has actually
      translated into program and/or policy changes. It describes 2 key areas where
      this is the case: 1) in defining the "window of opportunity" for nutrition
      interventions and changing policy regarding the targeting of nutrition
      interventions; and 2) in building the economic argument for investing in early
      childhood nutrition. It concludes that the study contributed most of the research
      evidence supporting the change in policy adopted by the U.S. government in 2009,
      which encourages the targeting of food-assisted maternal and child health and
      nutrition programs to pregnant mothers and children under 2 y of age. The paper
      reviews the process and the complementary evidence that led to this policy
      change. The Oriente Study also provides the first direct, and the strongest,
      evidence supporting the economic argument in favor of investing in early child
      nutrition. The results show a direct link between improved nutrition in early
      childhood and persistent benefits in adult physical status, schooling, cognitive
      skills, and economic productivity. It is hoped that, given the multiple shocks
      currently affecting the poor, these powerful results will help stimulate greater
      investments in maternal and child nutrition in the short term.

PMID- 20032475
TI  - Probability, plausibility, and adequacy evaluations of the Oriente Study
      demonstrate that supplementation improved child growth.
AB  - This article presents evidence that the high-nutrient supplement in the Oriente
      study (Atole) improved child growth. The evidence is presented at 4 levels. There
      was a causal effect of the intervention on child length, as assessed by
      probability analyses of the randomized, controlled trial (P < 0.05). The
      plausibility analyses, which included an examination of wasting, showed that the
      nutritional impact was due to the Atole, especially in those who were <3 y old
      and who suffered from diarrhea. The adequacy analyses revealed excellent
      biological efficacy of the Atole at the individual level. At the level of the
      whole population, the efficacy of impact was much less, because many children did
      not participate fully in the supplementation program. The external validity of
      the biological impact is likely to be good for populations with similar diets and
      medical care.

PMID- 20032476
TI  - Sesamin inhibits bacterial formylpeptide-induced inflammatory responses in a
      murine air-pouch model and in THP-1 human monocytes.
AB  - The reaction of human leukocytes to chemoattractants is an important component of
      the host immune response and also plays a crucial role in the development of
      inflammation. Sesamin has been shown to inhibit lipid peroxidation and regulate
      cytokine production. In this study, we examined the effect of sesamin on
      inflammatory responses elicited by the bacterial chemotactic peptide N-formyl
      methionyl-leucyl-phenylalanine (fMLF) in vitro and in vivo and explored the
      mechanisms involved. fMLF is recognized by a human G protein-coupled receptor
      formyl peptide receptor (FPR) on phagocytic leukocytes. Sesamin at concentrations
      between 12.5 and 50 micromol/L inhibited fMLF-induced chemotaxis of human
      monocyte cell line THP-1 differentiated with dibutyryl cyclic AMP (P < 0.01).
      Similarly, sesamin inhibited FPR-transfected rat basophilic leukemia cell
      [epitope-tagged human FPR (ETFR) cell] migration toward fMLF (P < 0.01). In fMLF
      induced inflammation in a murine air-pouch model, intraperitoneal administration
      of sesamin (12 mgkg(-1)d(-1) for 2 d) suppressed leukocyte infiltration into the
      air pouch induced by fMLF [(62.89 +/- 7.93) x 10(4) vs. (19.67 +/- 4.43) x 10(4)
      cells/air pouch; n = 9; P < 0.001]. Ca(2+) mobilization and mitogen-activated
      protein kinase extracellular signal-regulated kinase (ERK1/2) activation are
      involved in fMLF-induced leukocyte migration. Pretreatment of ETFR cells with
      sesamin inhibited fMLF-induced ERK1/2 phosphorylation in a dose-dependent manner
      but did not affect fMLF-induced Ca(2+) flux. Electrophoretic mobility shift assay
      showed that pretreatment of THP-1 cells with sesamin dose dependently inhibited
      fMLF-induced nuclear factor-kappaB (NF-kappaB) activation. These results suggest
      that sesamin inhibits leukocyte activation by fMLF through ERK1/2- and NF-kappaB
      related signaling pathways and thus is a potential compound for the management of
      inflammatory diseases.

PMID- 20032477
TI  - Leptin receptor polymorphisms interact with polyunsaturated fatty acids to
      augment risk of insulin resistance and metabolic syndrome in adults.
AB  - The leptin receptor (LEPR) is associated with insulin resistance, a key feature
      of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk.
      The objective was to investigate the relationship among LEPR polymorphisms,
      insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of
      dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100,
      rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and
      rs8179183), biochemical measurements, and plasma fatty acid profiles were
      determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n =
      1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the
      minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05-2.57; P = 0.028],
      which may be accounted for by their increased risk of elevated insulin
      concentrations (OR 2.40; 95% CI: 1.28-4.50; P = 0.006) and insulin resistance (OR
      = 2.15; 95% CI: 1.18-3.90; P = 0.012). Low (less than median) plasma (n-3) and
      high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity
      to hyperinsulinemia (OR 2.92-2.94) and insulin resistance (OR 3.40-3.47).
      Interestingly, these associations were abolished against a high (n-3) or low (n
      6) PUFA background. Importantly, we replicated some of these findings in an
      independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated
      with insulin resistance, which may predispose to increased MetS risk. Novel gene
      nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic
      influences were more evident in individuals with low plasma (n-3) or high plasma
      (n-6) PUFA.

PMID- 20032478
TI  - Serum lipid and blood pressure responses to quercetin vary in overweight patients
      by apolipoprotein E genotype.
AB  - Our objective was to examine the effect of a quercetin supplementation on blood
      pressure, lipid metabolism, markers of oxidative stress, inflammation, and body
      composition in an at-risk population of 93 overweight-obese volunteers aged 25-65
      y with metabolic syndrome traits in relation to apolipoprotein (apo) E genotype.
      Participants were randomized to receive 150 mg/d quercetin in a double-blinded,
      placebo-controlled, crossover trial with 6-wk treatment periods separated by a 5
      wk washout period. Retrospectively, 5 apoE genotype variants were found
      (epsilon2/epsilon3, n = 3; epsilon3/epsilon3, n = 60; epsilon3/epsilon4, n = 23;
      epsilon2/epsilon4, n = 4; and epsilon4/epsilon4, n = 3). Participants were
      classified into the following 3 apoE phenotypes: apoE2 (n = 3), apoE3 (n = 60),
      and apoE4 (n = 26). Data were analyzed for apoE3 and apoE4 subgroups. Quercetin
      decreased systolic blood pressure by 3.4 mm Hg (P < 0.01) in the apoE3 group,
      whereas no significant effect was observed in the apoE4 group. Quercetin
      decreased serum HDL cholesterol (P < 0.01) and apoA1 (P < 0.01) and increased the
      LDL:HDL cholesterol ratio (P < 0.05) in the apoE4 subgroup, whereas the apoE3
      subgroup had no significant changes in these variables. Quercetin significantly
      decreased plasma oxidized LDL and tumor necrosis factor-alpha in the apoE3 and
      apoE4 groups, whereas no significant inter-group differences were found. Serum C
      reactive protein and nutritional status (body weight, waist circumference, fat
      mass, fat-free mass) were unaffected compared with placebo. In conclusion,
      quercetin exhibited blood pressure-lowering effects in overweight-obese carriers
      of the apo epsilon3/epsilon3 genotype but not in carriers of the epsilon4 allele.
      Furthermore, quercetin supplementation resulted in a reduction in HDL cholesterol
      and apoA1 in apo epsilon4 carriers.

PMID- 20032479
TI  - A bovine whey protein extract stimulates human neutrophils to generate bioactive
      IL-1Ra through a NF-kappaB- and MAPK-dependent mechanism.
AB  - Innate immunity depends on the efficiency of neutrophils to be activated rapidly
      to restore homeostasis. It can benefit from priming agents that enhance
      neutrophil capacity to respond more efficiently to a subsequent stimulation.
      Among natural products, a bovine whey protein extract (WPE) has been shown to
      prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis,
      oxidative burst, and degranulation. These leukocytes are also an important source
      of cytokines, some of which have antiinflammatory functions. We investigated the
      role of WPE, as well as its mechanisms of action, on the production of
      interleukin (IL)-1 receptor antagonist (IL-1Ra) by neutrophils in vitro. WPE dose
      dependently stimulated de novo synthesis and release of IL-1Ra by normal human
      blood neutrophils. Among the major proteins present in WPE, beta-lactoglobulin
      (beta-LG) and alpha-lactalbumin (alpha-LA) were the only active components. They
      had additive effects that exactly reproduced those of WPE. Similarly to WPE, they
      also stimulated the accumulation of IL-1beta, IL-8, IL-6, macrophage inflammatory
      protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha. However,
      neutrophils incubated with WPE, beta-LG, and alpha-LA produced IL-1Ra in excess
      of IL-1beta and the ratio IL-1Ra:IL-1beta increased linearly. The amounts of IL
      1Ra stimulated by WPE or beta-LG + alpha-LA significantly reduced the IL-1
      activity in EL4 cells. Inhibitors of p38 and extracellular signal-regulated
      kinases (ERK)1/2 mitogen-activated protein kinase, and nuclear factor-kappaB
      cascades reduced neutrophil production of IL-1Ra. Our data suggest that WPE,
      through beta-LG + alpha-LA, has immunomodulatory properties and the potential to
      increase host defenses.

PMID- 20032480
TI  - Maternal supplementation differentially affects the mother and newborn.
AB  - Although studying the effect of supplementation on maternal health or the outcome
      of pregnancy was not a primary goal of the Institute of Nutrition of Central
      America and Panama Oriente Longitudinal Study, many important findings in these
      areas were produced. As part of the study, a food supplementation program was
      implemented. Two villages received Atole, a gruel containing protein and energy,
      and 2 matched villages received a refreshing, low-energy drink containing no
      protein. Both drinks contained micronutrients. Some women did not choose to
      consume the supplements and those who did consumed widely varying amounts. More
      volume of Fresco was consumed than Atole. The energy in the supplements improved
      birthweight, with no apparent additional benefit from protein or micronutrients.
      Researchers identified several groups of women who benefited from supplementation
      more than others by having babies with higher birthweights, including those with
      poorer current nutritional status and those who consumed high amounts of the
      supplement continuously from one pregnancy to the next. Results from the study
      provided an early indication that supplementation might increase the duration of
      gestation and, thus, reduce preterm birth. On the other hand, maternal
      supplementation did not substantially alter the duration of postpartum amenorrhea
      once concurrent infant supplementation was taken into account. Finally, findings
      from this study provided evidence of a biological trade-off between maintenance
      of maternal nutritional status and increasing fetal size that was responsive to
      both current maternal nutritional status and supplement intake but not to the
      mother's nutritional status earlier in life.

PMID- 20032481
TI  - The sex-specific role of plasma folate in mediating the association of dietary
      quality with depressive symptoms.
AB  - Folate deficiency has been implicated in the etiology of unipolar depression. In
      this study, we attempted to cross-link plasma folate, depressive symptoms, and
      dietary quality (or dietary intake of folate) together in a comprehensive
      framework, while examining effect modification of those associations by sex. This
      was a cross-sectional, population-based study of 1681 participants aged 30-64 y
      (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study).
      Participants were administered the Center for Epidemiologic Studies Depression
      scale (CES-D). Measures of plasma folate and dietary intakes (2 24-h recalls)
      from which the 2005-Healthy Eating Index (HEI) was computed were available.
      Multivariate logistic regression and structural equation modeling (SM) were
      conducted. Compared with the lowest tertile, the middle and uppermost tertiles of
      plasma folate were associated with a 39-40% reduced odds of elevated CES-D (> or
      =16) among women [adjusted odds ratio (T(3) vs. T(1)) = 0.60 (95% CI = 0.42
      0.86); P = 0.006]. Confounding of this association by HEI(total) was noted among
      both men and women, although dietary folate did not confound this association
      appreciably. In SM, plasma folate completely mediated the inverse HEI(total)-CES
      D association among men only, specifically for HEI(2) (higher intakes of whole
      fruits), HEI(3) (total vegetables), HEI(5) (total grains), HEI(6) (whole grains),
      HEI(7) (milk), and HEI(12) (lower discretionary energy). Among women, HEI(total)
      and 4 components had an inverse direct effect on CES-D score, suggesting a
      mechanism that is independent of plasma folate. Depressive symptoms in our study
      may be alleviated by improving overall dietary quality, with plasma folate
      playing a potential mediating role only among men.

PMID- 20032482
TI  - Introduction: the development and legacy of the INCAP Oriente Studies 1969-2009.

PMID- 20032483
TI  - All-trans retinoic acid lowers serum retinol-binding protein 4 concentrations and
      increases insulin sensitivity in diabetic mice.
AB  - Recent investigations have demonstrated that elevated serum retinol-binding
      protein 4 (RBP4) secreted from adipose tissue plays a role in the development of
      systemic insulin resistance, and lowering RBP4 improves insulin sensitivity.
      These observations provide a rationale for the development of new antidiabetic
      agents aimed at reducing serum RBP4 concentrations. In this study, we sought to
      determine whether retinoic acid (RA) administration decreases serum RBP4 and
      suppresses insulin resistance in diabetic ob/ob mice. All-trans RA [100
      mug/(moused) in corn oil] was administered by stomach intubation to a group of
      ob/ob mice, with the control group receiving the vehicle for 16 d. Body weight
      and food intake were monitored. Glucose and insulin tolerance tests were
      performed. We quantified serum RBP4 and retinol by Western blotting and HPLC,
      respectively. RA treatment reduced body weight (P < 0.05), basal serum glucose (P
      < 0.001), serum retinol (P < 0.01), and RBP4 (P < 0.05). It improved insulin
      sensitivity and decreased the retinol:RBP4 ratio (P < 0.05). These studies
      suggest that RA is an effective antidiabetic agent that could be considered in
      the treatment of type 2 diabetes.

PMID- 20032484
TI  - Nutritional stimulation of milk protein yield of cows is associated with changes
      in phosphorylation of mammary eukaryotic initiation factor 2 and ribosomal s6
      kinase 1.
AB  - Production of protein by the lactating mammary gland is stimulated by intake of
      dietary energy and protein. Mass-action effects of essential amino acids (EAA)
      cannot explain all of the nutritional response. Protein synthesis in tissues of
      growing animals is regulated by nutrients through the mammalian target of
      rapamycin (mTOR) and integrated stress response (ISR) networks. To explore if
      nutrients signal through the mTOR and ISR networks in the mammary gland in vivo,
      lactating cows were feed-deprived for 22 h and then infused i.v. for 9 h with
      EAA+ glucose (Glc), Glc only, l-Met+l-Lys, l-His, or l-Leu. Milk protein yield
      was increased 33 and 27% by EAA+Glc and Glc infusions, respectively. Infusions of
      Met+Lys and His generated 35 and 41%, respectively, of the EAA+Glc response.
      Infusion of EAA+Glc reduced phosphorylation of the ISR target, eukaryotic
      initiation factor(eIF) 2, in mammary tissue and increased phosphorylation of the
      mTOR targets, ribosomal S6 kinase 1 (S6K1) and S6. Both responses are stimulatory
      to protein synthesis. Glucose did not significantly increase mammary S6K1
      phosphorylation but reduced eIF2 phosphorylation by 62%, which implicates the ISR
      network in the stimulation of milk protein yield. In contrast, the EAA infusions
      increased (P < 0.05) or tended to increase (P < 0.1) mammary mTOR activity and
      only His, like Glc, decreased eIF2 phosphorylation by 62%. Despite activation of
      these protein synthesis signals to between 83 and 127% of the EAA+Glc response,
      EAA infusions produced less than one-half of the milk protein yield response
      generated by EAA+Glc, indicating that ISR and mTOR networks exert only a portion
      of the control over protein yield.

PMID- 20032486
TI  - History and early development of INCAP.
AB  - Nevin Scrimshaw was the founding Director of the Institute of Nutrition of
      Central America and Panama (INCAP), serving as Director from 1949 to 1961. In
      this article, he reviews the history of the founding of INCAP, including the role
      of the Rockefeller and Kellogg Foundations, the Central American governments, and
      the Pan American Health Organization. The objectives pursued by INCAP in its
      early years were to assess the nutrition and related health problems of Central
      America, to carry out research to find practical solutions to these problems, and
      to provide technical assistance to its member countries to implement solutions.
      INCAP pursued a strategy of selecting promising Central Americans for advanced
      education and training in the US who assumed positions of leadership on their
      return. After this early phase, talented non-Central Americans of diverse origins
      were brought to INCAP, as well as additional researchers from the region. Growth
      of INCAP, as reflected in its annual budget and in the physical plant, was rapid
      and this was accompanied by high scientific productivity. Several field studies
      were launched that contributed impetus and design elements for the Oriente
      Longitudinal Study, which is the focus of this supplement.

PMID- 20032485
TI  - Food insecurity is associated with chronic disease among low-income NHANES
      participants.
AB  - Food insecurity refers to the inability to afford enough food for an active,
      healthy life. Numerous studies have shown associations between food insecurity
      and adverse health outcomes among children. Studies of the health effects of food
      insecurity among adults are more limited and generally focus on the association
      between food insecurity and self-reported disease. We therefore examined the
      association between food insecurity and clinical evidence of diet-sensitive
      chronic disease, including hypertension, hyperlipidemia, and diabetes. Our
      population-based sample included 5094 poor adults aged 18-65 y participating in
      the NHANES (1999-2004 waves). We estimated the association between food
      insecurity (assessed by the Food Security Survey Module) and self-reported or
      laboratory/examination evidence of diet-sensitive chronic disease using Poisson
      regression. We adjusted the models to account for differences in age, gender,
      race, educational attainment, and income. Food insecurity was associated with
      self-reported hypertension [adjusted relative risk (ARR) 1.20; 95% CI, 1.04-1.38]
      and hyperlipidemia (ARR 1.30; 95% CI, 1.09-1.55), but not diabetes (ARR 1.19; 95%
      CI, 0.89-1.58). Food insecurity was associated with laboratory or examination
      evidence of hypertension (ARR 1.21; 95% CI, 1.04-1.41) and diabetes (ARR 1.48;
      95% CI, 0.94-2.32). The association with laboratory evidence of diabetes did not
      reach significance in the fully adjusted model unless we used a stricter
      definition of food insecurity (ARR 2.42; 95% CI, 1.44-4.08). These data show that
      food insecurity is associated with cardiovascular risk factors. Health policy
      discussions should focus increased attention on ability to afford high-quality
      foods for adults with or at risk for chronic disease.

PMID- 20032488
TI  - Estimation of antioxidant intakes from diet and supplements in U.S. adults.
AB  - The importance of antioxidants in reducing risks of chronic diseases has been
      well established; however, antioxidant intakes by a free-living population have
      not yet been estimated adequately. In this study, we aimed to estimate total
      antioxidant intakes from diets and supplement sources in the U.S. population. The
      USDA Flavonoid Database, food consumption data, and dietary supplement use data
      of 8809 U.S. adults aged >/=19 y in NHANES 1999-2000 and 2001-2002 were used in
      this study. Daily total antioxidant intake was 208 mg vitamin C (46 and 54% from
      diets and supplements, respectively), 20 mg alpha-tocopherol (36 and 64), 223 mug
      retinol activity equivalents carotenes (86 and 14), 122 mug selenium (89 and 11),
      and 210 mg flavonoids (98 and 2). Antioxidant intakes differed among
      sociodemographic subgroups and lifestyle behaviors. Energy-adjusted dietary
      antioxidant intakes were higher in women, older adults, Caucasians, nonconsumers
      of alcohol (only for vitamin C and carotenes), nonsmokers (only for vitamin C,
      vitamin E, and carotenes), and in those with a higher income and exercise level
      (except for flavonoids) than in their counterparts (P < 0.05). Consumption of
      fruits, vegetables, and whole grains may be a good strategy to increase
      antioxidant intake. The possible association between antioxidant intake and the
      prevalence of chronic diseases should be investigated further.

PMID- 20032487
TI  - Associations between multiple indicators of socioeconomic status and obesity in
      young adult Filipinos vary by gender, urbanicity, and indicator used.
AB  - More research is needed on the socio-environmental determinants of obesity in
      lower- and middle-income countries. We used generalized estimating equations to
      evaluate the cross-sectional effect of urban residence and multiple individual
      level indicators of socioeconomic status (SES) on the odds of overweight or
      central adiposity in a birth cohort of young adult (mean age 21.5 y) Filipino
      males (n = 987) and females (n = 819) enrolled in the Cebu Longitudinal Health
      and Nutrition Survey. Overweight was defined as BMI >/=25 kg/m(2) and central
      adiposity was defined as a waist circumference >85 cm for males or >80 cm for
      females. Community-level urbanicity was measured on a continuous scale. Multiple
      indicators of SES included assets, income, education, and marital status. In the
      final multivariable models, assets and being married were positively related to
      overweight and central adiposity in males (P < 0.05), but being married was the
      only predictor of these outcomes in females. However, once the modifying effects
      of urban residence were accounted for, assets were positively related to
      overweight and central adiposity among the most rural women, but not in more
      urban women. Our results are consistent with a growing body of literature that
      suggests the relationship between SES and obesity is positive in lower-income
      contexts and inverse in higher-income contexts, particularly in females. The
      pattern of relationships we observed suggests that as the Philippines continues
      to develop economically, the public health impact of obesity will increase
      similarly to what has been observed in countries further along in their economic
      transition.

PMID- 20032489
TI  - Stimulation of muscle protein synthesis by prolonged parenteral infusion of
      leucine is dependent on amino acid availability in neonatal pigs.
AB  - The postprandial rise in amino acids, particularly leucine, stimulates muscle
      protein synthesis in neonates. Previously, we showed that a 1-h infusion of
      leucine increased protein synthesis, but this response was not sustained for 2 h
      unless the leucine-induced decrease in amino acids was prevented. To determine
      whether a parenteral leucine infusion can stimulate protein synthesis for a more
      prolonged, clinically relevant period if baseline amino acid concentrations are
      maintained, overnight food-deprived neonatal pigs were infused for 24 h with
      saline, leucine (400 mumol.kg(-1). h(-1)), or leucine with replacement amino
      acids. Amino acid replacement prevented the leucine-induced decrease in amino
      acids. Muscle protein synthesis was increased by leucine but only when other
      amino acids were supplied to maintain euaminoacidemia. Leucine did not affect
      activators of mammalian target of rapamycin (mTOR), i.e. protein kinase B, AMP
      activated protein kinase, tuberous sclerosis complex 2, or eukaryotic elongation
      factor 2. There was no effect of treatment on the association of mTOR with
      regulatory associated protein of mammalian target of rapamycin (raptor), G
      protein beta subunit-like protein, or rictor or the phosphorylation of raptor or
      proline-rich Akt substrate of 40 kDa. Phosphorylation of mTOR and its downstream
      targets, eukaryotic initiation factor (eIF) 4E binding protein and ribosomal
      protein S6 kinase, and the eIF4E . eIF4G association were increased and eIF2alpha
      phosphorylation was reduced by leucine and was not further altered by correcting
      for the leucine-induced hypoaminoacidemia. Thus, prolonged parenteral infusion of
      leucine activates mTOR and its downstream targets in neonatal skeletal muscle,
      but the stimulation of protein synthesis also is dependent upon amino acid
      availability.

PMID- 20032490
TI  - The role of innovation and technology in meeting individual nutritional needs.
AB  - Few Americans meet the recommendations of the Dietary Guidelines for Americans
      and many do not know how to apply food and nutrition information to develop a
      personal approach to preventing diet/lifestyle-related diseases. In a time of
      rapid technologic advancement and rewards for innovation, a critical opportunity
      in food and nutrition science exists for improving health and reducing disease
      risk. The National Center for Food Safety and Technology (NCFST) recently
      established the Health Promoting Foods research platform to support the
      availability of safe food by using emerging technologies for improving food
      quality and consumer choice. A workshop convened with leading regulators and
      nutrition, genetic, medical, toxicological, behavioral, and consumer scientists
      to: discuss challenges facing personalized nutrition and health, develop
      strategies to overcome challenges using innovations in food and information
      technology, and define and prioritize a short- and long-term research agenda for
      the research platform. The workshop included presentations and in-depth
      discussions on the state of the science in genomics, behavior, food, and
      information technology. Workshop participants identified gaps, intersections, and
      new opportunities for delivering individualized food-based solutions that would
      be more accessible, affordable, and convenient. The research agenda, which was
      developed within a framework of providing information and guidance to the food
      and associated industries, supporting the process for health-related claims,
      building consumer confidence in data and food-health information, and providing a
      pathway for implementation of the US Dietary Guidelines for Americans and other
      public policies, reflects the commitment of the community, government, food
      industry, health organizations, and academia to improving health.

PMID- 20032491
TI  - Increased consumption of fatty and lean fish reduces serum C-reactive protein
      concentrations but not inflammation markers in feces and in colonic biopsies.
AB  - Fish consumption is associated with a reduced colorectal cancer risk. A possible
      mechanism by which fish consumption could decrease colorectal cancer risk is by
      reducing inflammation. However, thus far, intervention studies investigating both
      systemic and local gut inflammation markers are lacking. Our objective in this
      study was to investigate the effects of fatty and lean fish consumption on
      inflammation markers in serum, feces, and gut. In an intervention study,
      participants were randomly allocated to receive dietary advice (DA) plus either
      300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or
      only DA. Serum C-reactive protein (CRP) concentrations were measured pre- and
      postintervention (n = 161). In a subgroup (n = 52), we explored the effects of
      the fish intervention on fecal calprotectin and a wide range of cytokines and
      chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were
      lower in the salmon (-0.5 mg/L; 95% CI -0.9, -0.2) and cod (-0.4 mg/L; 95% CI 
      0.7, 0.0) groups compared with the DA group. None of the inflammation markers in
      fecal water and colonic biopsies differed between the DA group and the groups
      that consumed extra fish. In conclusion, increasing salmon or cod consumption for
      6 mo resulted in lower concentrations of the systemic inflammation marker CRP.
      However, exploratory analysis of local markers of inflammation in the colon or
      feces did not reveal an effect of fish consumption.

PMID- 20032492
TI  - Late introduction of complementary feeding, rather than duration of
      breastfeeding, may protect against adult overweight.
AB  - BACKGROUND: Early nutrition may affect the risk of overweight in later life.
      OBJECTIVE: The objective was to explore the effect of the duration of
      breastfeeding (BF) and age at introduction of complementary feeding (CF) on body
      mass index (BMI) during childhood through adulthood. DESIGN: The study was based
      on a subsample of the Copenhagen Perinatal Cohort established in 1959-1961 (n =
      5068). Information on BF and available information on CF (age of introduction of
      "spoon-feeding," "vegetables," "egg," "meat," and "firm food") and several
      covariates were collected in infancy and linked with information on BMI from
      follow-up examinations in childhood and adulthood at age 42 y. RESULTS: The
      median (10th, 90th percentiles) durations of any BF and age at introduction of
      spoon-feeding were 2.50 (0.23, 6.50) and 3.50 (2.00, 6.00) mo, respectively.
      After 1 y of age and throughout childhood and adolescence, no association between
      BF and BMI was found in regression models also adjusted for age at introduction
      of spoon-feeding and covariates. The risk of overweight at age 42 y decreased or
      tended to decrease with increasing age (in mo) at introduction of spoon-feeding
      [odds ratio (OR): 0.94; 95% CI: 0.86, 1.02], vegetables (OR: 0.90; 95% CI: 0.81,
      0.98), meat (OR: 0.93; 95% CI: 0.87, 1.00), and firm food (OR: 0.92; 95% CI:
      0.86, 0.98) but not egg (OR: 0.98; 95% CI: 0.91, 1.05). CONCLUSION: The findings
      of this study suggest that introduction of CF at a later age (within the range of
      2 to 6 mo) is protective against overweight in adulthood but do not support a
      protective effect of a longer duration of BF.

PMID- 20032493
TI  - TCF7L2 rs7903146-macronutrient interaction in obese individuals' responses to a
      10-wk randomized hypoenergetic diet.
AB  - BACKGROUND: Transcription factor 7-like 2 (TCF7L2) rs7903146 associates with type
      2 diabetes and may operate via impaired glucagon-like peptide 1 secretion, which
      is stimulated more by fat than by carbohydrate ingestion. OBJECTIVE: The
      objective was to examine the interaction between TCF7L2 rs7903146 and dietary fat
      and carbohydrate [high-fat, low-carbohydrate: 40-45% of energy as fat (HF);
      compared with low-fat, high-carbohydrate: 20-25% of energy as fat (LF)] in obese
      individuals' responses to a 10-wk hypoenergetic diet (-600 kcal/d). DESIGN:
      European, obese participants (n = 771) were randomly assigned to receive an HF or
      an LF diet. Body weight, fat mass (FM), fat-free mass (FFM), waist circumference
      (WC), resting energy expenditure (REE), fasting fat oxidation in percentage of
      REE (FatOx), homeostasis model assessed insulin release (HOMA-beta), and HOMA
      insulin resistance (HOMA-IR) were determined at baseline and after the
      intervention; 739 individuals were genotyped for rs7903146. RESULTS: Average
      weight loss was 6.9 kg with the LF and 6.6 kg with the HF (difference between
      diets, NS) diet. Among individuals who were homozygous for the T-risk allele,
      those in the HF diet group experienced smaller weight losses (Deltaweight) (2.6
      kg; P = 0.009; n = 622), smaller DeltaFFM (1.6 kg; P = 0.027; n = 609), smaller
      DeltaWC (3.3 cm; P = 0.010; n = 608), and a smaller DeltaHOMA-IR (1.3 units; P =
      0.004; n = 615) than did the LF diet group. For C allele carriers, there were no
      differences between the HF and LF diet groups. For the HF diet group, each
      additional T allele was associated with a reduced loss of FM (0.67 kg; P = 0.019;
      n = 609). TCF7L2 rs7903146 was not associated with DeltaREE, DeltaFatOx,
      DeltaHOMA-beta, or dropout. CONCLUSION: Our results suggest that obese
      individuals who are homozygous for the TCF7L2 rs7903146 T-risk allele are more
      sensitive to LF than to HF weight-loss diets.

PMID- 20032494
TI  - Fasting urine pH is independent of insulin sensitivity.
AB  - BACKGROUND: It has recently been suggested that a low urine pH be added to the
      abnormalities linked to insulin resistance. This conclusion is based on the
      finding of a low urine pH in individuals with clinical syndromes associated with
      insulin resistance and not on studies in which a direct measure of insulin
      sensitivity was shown to be significantly related to differences in urine pH.
      OBJECTIVE: To address this issue, we quantified insulin-mediated glucose uptake
      (IMGU) by using the insulin suppression test in 96 apparently healthy,
      nondiabetic individuals and defined its relation to fasting urine pH. DESIGN:
      Urine samples were collected and analyzed from a cohort of healthy subjects
      within a narrow body mass index range who were recruited to determine insulin
      sensitivity. RESULTS: There was an approximate 6-fold variation in values for
      IMGU in this population, with no relation to urine pH (r = 0.02). Furthermore,
      there was no relation between body mass index, as a surrogate estimate of insulin
      resistance, and urine pH (r = 0.06). CONCLUSION: On the basis of these findings,
      we question the view that a low urine pH be added to the abnormalities linked to
      insulin resistance in low-risk populations.

PMID- 20032495
TI  - Gene-nutrient interactions in the metabolic syndrome: single nucleotide
      polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to
      modulate insulin resistance.
AB  - BACKGROUND: Progression of the metabolic syndrome (MetS) is determined by genetic
      and environmental factors. Gene-environment interactions may be important in
      modulating the susceptibility to the development of MetS traits. OBJECTIVE: Gene
      nutrient interactions were examined in MetS subjects to determine interactions
      between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ)
      and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and
      their effects on MetS characteristics. DESIGN: Plasma fatty acid composition,
      insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ,
      ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis
      of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics,
      and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and
      Economic Analysis) dietary intervention study and were repeated in 1754 subjects
      from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Mineraux
      AntioXydants) case-control study (http://www.ucd.ie/lipgene). RESULTS: Single SNP
      effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids,
      and waist circumference were significantly different between genotypes for 2 SNPs
      (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both
      of these SNPs were identified as having degrees of insulin resistance, as
      measured by the homeostasis model assessment of insulin resistance, that were
      highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA
      dependent association between ADIPOR1 rs10920533 and insulin resistance was
      replicated in cases with MetS from a separate independent study, which was an
      association not present in controls. CONCLUSIONS: A reduction in plasma SFAs
      could be expected to lower insulin resistance in MetS subjects who are minor
      allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized
      dietary advice to decrease SFA consumption in these individuals may be
      recommended as a possible therapeutic measure to improve insulin sensitivity.
      This trial was registered at clinicaltrials.gov as NCT00429195.

PMID- 20032496
TI  - Neutral and acidic oligosaccharides in preterm infants: a randomized, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Serious infectious morbidity is high in preterm infants. Enteral
      supplementation of prebiotics may reduce the incidence of serious infections,
      especially infections related to the gastrointestinal tract. OBJECTIVE: The
      objective was to determine the effect of enteral supplementation of a prebiotic
      mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic
      oligosaccharides (AOS) on serious infectious morbidity in preterm infants.
      DESIGN: In a randomized controlled trial, preterm infants (gestational age <32 wk
      and/or birth weight <1500 g) received enteral supplementation of 80%
      (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin)
      between days 3 and 30 of life. Serious infectious morbidity was defined as a
      culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The
      analysis was performed by intention-to-treat and per-protocol, defined as > or
      =50% supplementation dose during the study period. RESULTS: In total, 113 preterm
      infants were included. Baseline and nutritional characteristics were not
      different between groups. In the intention-to-treat analysis, the incidence of >
      or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious
      infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS
      supplemented and placebo groups. In the per-protocol analysis, there was a trend
      toward a lower incidence of > or =1 serious endogenous infection and > or =2
      serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in
      the placebo group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: Enteral
      supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of
      serious infectious morbidity in preterm infants. However, there was a trend
      toward a lower incidence of serious infectious morbidity, especially for
      infections with endogenous bacteria. This finding suggests a possible beneficial
      effect that should be evaluated in a larger study. This trial was registered at
      isrctn.org as ISRCTN16211826.

PMID- 20032497
TI  - KLF2-induced actin shear fibers control both alignment to flow and JNK signaling
      in vascular endothelium.
AB  - The shear stress-induced transcription factor Kruppel-like factor 2 (KLF2)
      confers antiinflammatory properties to endothelial cells through the inhibition
      of activator protein 1, presumably by interfering with mitogen-activated protein
      kinase (MAPK) cascades. To gain insight into the regulation of these cascades by
      KLF2, we used antibody arrays in combination with time-course mRNA microarray
      analysis. No gross changes in MAPKs were detected; rather, phosphorylation of
      actin cytoskeleton-associated proteins, including focal adhesion kinase, was
      markedly repressed by KLF2. Furthermore, we demonstrate that KLF2-mediated
      inhibition of Jun NH(2)-terminal kinase (JNK) and its downstream targets ATF2/c
      Jun is dependent on the cytoskeleton. Specifically, KLF2 directs the formation of
      typical short basal actin filaments, termed shear fibers by us, which are
      distinct from thrombin- or tumor necrosis factor-alpha-induced stress fibers.
      KLF2 is shown to be essential for shear stress-induced cell alignment,
      concomitant shear fiber assembly, and inhibition of JNK signaling. These findings
      link the specific effects of shear-induced KLF2 on endothelial morphology to the
      suppression of JNK MAPK signaling in vascular homeostasis via novel actin shear
      fibers.

PMID- 20032498
TI  - Molecular remission is an independent predictor of clinical outcome in patients
      with mantle cell lymphoma after combined immunochemotherapy: a European MCL
      intergroup study.
AB  - The prognostic impact of minimal residual disease (MRD) was analyzed in 259
      patients with mantle cell lymphoma (MCL) treated within 2 randomized trials of
      the European MCL Network (MCL Younger and MCL Elderly trial). After rituximab
      based induction treatment, 106 of 190 evaluable patients (56%) achieved a
      molecular remission (MR) based on blood and/or bone marrow (BM) analysis. MR
      resulted in a significantly improved response duration (RD; 87% vs 61% patients
      in remission at 2 years, P = .004) and emerged to be an independent prognostic
      factor for RD (hazard ratio = 0.4, 95% confidence interval, 0.1-0.9, P = .028).
      MR was highly predictive for prolonged RD independent of clinical response
      (complete response [CR], complete response unconfirmed [CRu], partial response
      [PR]; RD at 2 years: 94% in BM MRD-negative CR/CRu and 100% in BM MRD-negative
      PR, compared with 71% in BM MRD-positive CR/CRu and 51% in BM MRD-positive PR, P
      = .002). Sustained MR during the postinduction period was predictive for outcome
      in MCL Younger after autologous stem cell transplantation (ASCT; RD at 2 years
      100% vs 65%, P = .001) and during maintenance in MCL Elderly (RD at 2 years: 76%
      vs 36%, P = .015). ASCT increased the proportion of patients in MR from 55%
      before high-dose therapy to 72% thereafter. Sequential MRD monitoring is a
      powerful predictor for treatment outcome in MCL. These trials are registered at
      www.clinicaltrials.gov as #NCT00209222 and #NCT00209209.

PMID- 20032499
TI  - Critical requirement for the Wiskott-Aldrich syndrome protein in Th2 effector
      function.
AB  - Patients with Wiskott-Aldrich syndrome (WAS) have numerous immune cell
      deficiencies, but it remains unclear how abnormalities in individual cell types
      contribute to the pathologies of WAS. In T cells, the WAS protein (WASp)
      regulates actin polymerization and transcription, and plays a role in the
      dynamics of the immunologic synapse. To examine how these events influence CD4
      function, we isolated the WASp deficiency to CD4(+) T cells by adoptive transfer
      into wild-type mice to study T-cell priming and effector function. WAS(-/-)
      CD4(+) T cells mediated protective T-helper 1 (Th1) responses to Leishmania major
      in vivo, but were unable to support Th2 immunity to Nippostrongylus brasiliensis
      or L major. Mechanistically, WASp was not required for Th2 programming but was
      required for Th2 effector function. WAS(-/-) CD4(+) T cells up-regulated IL-4 and
      GATA3 mRNA and secreted IL-4 protein during Th2 differentiation. In contrast,
      cytokine transcription was uncoupled from protein production in WAS(-/-) Th2
      primed effectors. WAS(-/-) Th2s failed to produce IL-4 protein on restimulation
      despite elevated IL-4/GATA3 mRNA. Moreover, dominant-negative WASp expression in
      WT effector T cells blocked IL-4 production, but had no effect on IFNgamma. Thus
      WASp plays a selective, posttranscriptional role in Th2 effector function.

PMID- 20032500
TI  - Slug deficiency enhances self-renewal of hematopoietic stem cells during
      hematopoietic regeneration.
AB  - Both extrinsic and intrinsic mechanisms tightly govern hematopoietic stem cell
      (HSC) decisions of self-renewal and differentiation. However, transcription
      factors that can selectively regulate HSC self-renewal division after stress
      remain to be identified. Slug is an evolutionarily conserved zinc-finger
      transcription factor that is highly expressed in primitive hematopoietic cells
      and is critical for the radioprotection of these key cells. We studied the effect
      of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress
      conditions using serial functional assays. Here, we show that Slug deficiency
      does not disturb hematopoiesis or alter HSC homeostasis and differentiation in
      bone marrow but increases the numbers of primitive hematopoietic cells in the
      extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential
      but not its homing and differentiation ability. Furthermore, Slug deficiency
      increases HSC proliferation and repopulating potential in vivo after
      myelosuppression and accelerates HSC expansion during in vitro culture.
      Therefore, we propose that Slug is essential for controlling the transition of
      HSCs from relative quiescence under steady-state condition to rapid proliferation
      under stress conditions. Our data suggest that inhibition of Slug in HSCs may
      present a novel strategy for accelerating hematopoietic recovery, thus providing
      therapeutic benefits for patients after clinical myelosuppressive treatment.

PMID- 20032501
TI  - Clinical-grade production of human mesenchymal stromal cells: occurrence of
      aneuploidy without transformation.
AB  - Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro
      for tissue engineering or immunoregulatory purposes without standardized culture
      conditions or release criteria. Although human MSCs show poor susceptibility for
      oncogenic transformation, 2 recent studies described their capacity to accumulate
      chromosomal instability and to give rise to carcinoma in immunocompromised mice
      after long-term culture. We thus investigated the immunologic and genetic
      features of MSCs expanded with fetal calf serum and fibroblast growth factor or
      with platelet lysate in 4 cell-therapy facilities during 2 multicenter clinical
      trials. Cultured MSCs showed a moderate expression of human leukocyte antigen-DR
      without alteration of their low immunogenicity or their immunomodulatory
      capacity. Moreover, some transient and donor-dependent recurring aneuploidy was
      detected in vitro, independently of the culture process. However, MSCs with or
      without chromosomal alterations showed progressive growth arrest and entered
      senescence without evidence of transformation either in vitro or in vivo.

PMID- 20032502
TI  - An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13
      spacer domain identifies a binding site for the A2 domain of VWF.
AB  - In the majority of patients with acquired thrombotic thrombocytopenic purpura
      (TTP), antibodies are directed toward the spacer domain of ADAMTS13. We have
      previously shown that region Y658-Y665 is involved. We now show that replacement
      of R660, Y661, or Y665 with alanine in ADAMTS13 reduced/abolished the binding of
      2 previously isolated human monoclonal antibodies and polyclonal antibodies
      derived from plasma of 6 patients with acquired TTP. We investigated whether
      these residues also influenced cleavage of short von Willebrand factor (VWF)
      fragment substrate VWF115. An ADAMTS13 variant (R660A/Y661A/Y665A, ADAMTS13-RYY)
      showed a 12-fold reduced catalytic efficiency (k(cat)/K(m)) arising from greatly
      reduced (> 25-fold) binding, demonstrated by surface plasmon resonance. The
      influence of these residue changes on full-length VWF was determined with
      denaturing and flow assays. ADAMTS13-RYY had reduced activity in both, with
      proteolysis of VWF unaffected by autoantibody. Binding of ADAMTS13-RYY mutant to
      VWF was, however, similar to normal. Our results demonstrate that residues within
      Y658-Y665 of the ADAMTS13 spacer domain that are targeted by autoantibodies in
      TTP directly interact with a complementary exosite (E1660-R1668) within the VWF
      A2 domain. Residues R660, Y661, and Y665 are critical for proteolysis of short
      VWF substrates, but wider domain interactions also make important contributions
      to cleavage of full-length VWF.

PMID- 20032503
TI  - Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute
      myeloid leukemia.
AB  - Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t
      AML) have a poor prognosis with conventional therapy. Encouraging results are
      reported after allogeneic transplantation. We analyzed outcomes in 868 persons
      with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from
      1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment
      related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38
      44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years,
      respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29
      36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years,
      respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS
      and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in
      remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or
      a partially or well-matched unrelated donor. Five-year survival for subjects with
      none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31),
      21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data
      permit a more precise prediction of outcome and identify subjects most likely to
      benefit from allogeneic transplantation.

PMID- 20032504
TI  - The Mantle Cell Lymphoma International Prognostic Index (MIPI) is superior to the
      International Prognostic Index (IPI) in predicting survival following intensive
      first-line immunochemotherapy and autologous stem cell transplantation (ASCT).
AB  - Mantle cell lymphoma (MCL) has a heterogeneous clinical course. The recently
      proposed Mantle Cell Lymphoma International Prognostic Index (MIPI) predicted the
      survival of MCL better than the International Prognostic Index in MCL patients
      treated with conventional chemotherapy, but its validity in MCL treated with more
      intensive immunochemotherapy has been questioned. Applied here to 158 patients of
      the Nordic MCL2 trial of first-line intensive immunochemotherapy followed by high
      dose chemotherapy and autologous stem cell transplantation, the MIPI and the
      simplified MIPI (s-MIPI) predicted survival significantly better (P < .001) than
      the International Prognostic Index (P > .004). Both the MIPI and the s-MIPI
      mainly identified 2 risk groups, low and intermediate versus high risk, with the
      more easily applied s-MIPI being just as powerful as the MIPI. The MIPI(B)
      (biological), incorporating Ki-67 expression, identified almost half of the
      patients as high risk. We suggest that also a simplified MIPI(B) is feasible.

PMID- 20032505
TI  - Gene expression profiling-based dissection of MLL translocated and MLL germline
      acute lymphoblastic leukemia in infants.
AB  - Acute lymphoblastic leukemia (ALL) in infants (< 1 year) is characterized by a
      poor prognosis and a high incidence of MLL translocations. Several studies
      demonstrated the unique gene expression profile associated with MLL-rearranged
      ALL, but generally small cohorts were analyzed as uniform patient groups
      regardless of the type of MLL translocation, whereas the analysis of
      translocation-negative infant ALL remained unacknowledged. Here we generated and
      analyzed primary infant ALL expression profiles (n = 73) typified by
      translocations t(4;11), t(11;19), and t(9;11), or the absence of MLL
      translocations. Our data show that MLL germline infant ALL specifies a gene
      expression pattern that is different from both MLL-rearranged infant ALL and
      pediatric precursor B-ALL. Moreover, we demonstrate that, apart from a
      fundamental signature shared by all MLL-rearranged infant ALL samples, each type
      of MLL translocation is associated with a translocation-specific gene expression
      signature. Finally, we show the existence of 2 distinct subgroups among t(4;11)
      positive infant ALL cases characterized by the absence or presence of HOXA
      expression, and that patients lacking HOXA expression are at extreme high risk of
      disease relapse. These gene expression profiles should provide important novel
      insights in the complex biology of MLL-rearranged infant ALL and boost our
      progress in finding novel therapeutic solutions.

PMID- 20032506
TI  - Survival and relapse in patients with thrombotic thrombocytopenic purpura.
AB  - Survival of patients with thrombotic thrombocytopenic purpura (TTP) improved
      dramatically with plasma exchange treatment, revealing risk for relapse. The
      Oklahoma TTP Registry is a population-based inception cohort of all 376
      consecutive patients with an initial episode of clinically diagnosed TTP (defined
      as microangiopathic hemolytic anemia and thrombocytopenia with or without signs
      and symptoms of ischemic organ dysfunctions) for whom plasma exchange was
      requested, 1989 to 2008. Survival was not different between the first and second
      10-year periods for all patients (68% and 69%, P = .83) and for patients with
      idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261
      (93%) of 282 patients since 1995. Survival was not different between patients
      with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136
      of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor
      titer of 2 or more Bethesda units/mL was associated with lower survival (P =
      .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16
      of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors
      with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44
      survivors, ADAMTS13 deficiency during remission was not clearly related to
      subsequent relapse.

PMID- 20032507
TI  - Overview on practices in thalassemia intermedia management aiming for lowering
      complication rates across a region of endemicity: the OPTIMAL CARE study.
AB  - Despite recent advances in understanding the pathophysiologic mechanisms behind
      the thalassemia intermedia (TI) phenotype, data on the effects of treatment are
      deficient. To provide such data, we evaluated 584 TI patients for the
      associations between patient and disease characteristics, treatment received, and
      the rate of complications. The most common disease-related complications were
      osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and
      cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal
      liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes
      mellitus were less frequently observed. On multivariate analysis, older age and
      splenectomy were independently associated with an increased risk of most disease
      related complications. Transfusion therapy was protective for thrombosis, EMH,
      PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy
      was associated with an increased risk of endocrinopathy. Iron chelation therapy
      was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was
      associated with an increased risk of hypogonadism yet was protective for EMH,
      PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to
      the impact of age on complications in TI, and the beneficial role of splenectomy
      deserves revisiting. This study provides evidence that calls for prospective
      evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy
      in TI patients.

PMID- 20032508
TI  - Ischemia induces regulator of G protein signaling 2 (RGS2) protein upregulation
      and enhances apoptosis in astrocytes.
AB  - Regulator of G protein signaling (RGS) family members, such as RGS2, interact
      with Galpha subunits of heterotrimeric G proteins, accelerating the rate of GTP
      hydrolysis and attenuating the intracellular signaling triggered by the G protein
      coupled receptor-ligand interaction. They are also reported to regulate G protein
      effector interactions and form multiprotein signaling complexes. Ischemic stress
      induced changes in RGS2 expression have been described in astrocytes, and these
      changes are associated with intracellular signaling cascades, suggesting that
      RGS2 upregulation may be an important mechanism by which astrocytes may regulate
      RGS2 function in response to physiological stress. However, information on the
      functional roles of stress-induced modulation of RGS2 protein expression in
      astrocyte function is limited. We report the role of ischemic stress in RGS2
      protein expression in rat C6 astrocytoma cells and primary mouse astrocytes. A
      marked increase in RGS2 occurred after ischemic stress induced by chemicals
      (sodium azide and 2-deoxyglucose) or oxygen-glucose deprivation (OGD, real
      ischemia). RGS2 mRNA expression was markedly enhanced by 1 h of exposure to
      chemical ischemia or 6 h of OGD followed by 2 or 6 h of recovery, respectively.
      This enhanced expression in primary astrocytes and C6 cells was restored to
      baseline levels after 12 h of recovery from chemically induced ischemic stress or
      4-6 h of recovery from OGD. RGS2 protein was also significantly expressed at 12
      24 h of recovery from ischemic insult. Ischemia-induced RGS2 upregulation was
      associated with enhanced apoptosis. It significantly increased annexin V-positive
      cells, cleaved caspase-3, and enhanced DNA ladder formation and cell cycle
      arrest. However, a small interfering RNA (siRNA)-mediated RGS2 knockdown reversed
      the apoptotic cell death associated with ischemia-induced RGS2 upregulation.
      Upregulated RGS2 was significantly inhibited by SB-203580, a p38 MAPK inhibitor.
      Rottlerin, a potent inhibitor of PKCdelta, completely abrogated the increased
      RGS2 expression. We also examine whether ischemia-induced RGS2-mediated apoptosis
      is affected by siRNA-targeted endogenous PKCdelta downregulation or its
      phosphorylation. Although RGS2 upregulation was not affected, siRNA transfection
      significantly suppressed endogenous PKCdelta mRNA and protein expressions.
      Ischemia-induced PKCdelta phosphorylation and caspase-3 cleavage were dose
      dependently inhibited by PKCdelta knockdown, and this endogenous PKCdelta
      suppression reversed ischemia-induced annexin V-positive cells. This study
      suggests that ischemic stress increases RGS2 expression and that this condition
      contributes to enhanced apoptosis in C6 cells and primary astrocytes. The
      signaling it follows may involve PKCdelta and p38 MAPK pathways.

PMID- 20032509
TI  - PGC-1alpha plays a functional role in exercise-induced mitochondrial biogenesis
      and angiogenesis but not fiber-type transformation in mouse skeletal muscle.
AB  - Endurance exercise stimulates peroxisome proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) expression in skeletal muscle, and forced
      expression of PGC-1alpha changes muscle metabolism and exercise capacity in mice.
      However, it is unclear if PGC-1alpha is indispensible for endurance exercise
      induced metabolic and contractile adaptations in skeletal muscle. In this study,
      we showed that endurance exercise-induced expression of mitochondrial enzymes
      (cytochrome oxidase IV and cytochrome c) and increases of platelet endothelial
      cell adhesion molecule-1 (PECAM-1, CD31)-positive endothelial cells in skeletal
      muscle, but not IIb-to-IIa fiber-type transformation, were significantly
      attenuated in muscle-specific Pgc-1alpha knockout mice. Interestingly, voluntary
      running effectively restored the compromised mitochondrial integrity and
      superoxide dismutase 2 (SOD2) protein expression in skeletal muscle in Pgc-1alpha
      knockout mice. Thus, PGC-1alpha plays a functional role in endurance exercise
      induced mitochondrial biogenesis and angiogenesis, but not IIb-to-IIa fiber-type
      transformation in mouse skeletal muscle, and the improvement of mitochondrial
      morphology and antioxidant defense in response to endurance exercise may occur
      independently of PGC-1alpha function. We conclude that PGC-1alpha is required for
      complete skeletal muscle adaptations induced by endurance exercise in mice.

PMID- 20032510
TI  - Ca2+ influx via TRPC channels induces NF-kappaB-dependent A20 expression to
      prevent thrombin-induced apoptosis in endothelial cells.
AB  - NF-kappaB signaling is known to induce the expression of antiapoptotic and
      proinflammatory genes in endothelial cells (ECs). We have shown recently that
      Ca(2+) influx through canonical transient receptor potential (TRPC) channels
      activates NF-kappaB in ECs. Here we show that Ca(2+) influx signal prevents
      thrombin-induced apoptosis by inducing NF-kappaB-dependent A20 expression in ECs.
      Knockdown of TRPC1 expressed in human umbilical vein ECs with small interfering
      RNA (siRNA) suppressed thrombin-induced Ca(2+) influx and NF-kappaB activation in
      ECs. Interestingly, we observed that thrombin induced >25% of cell death
      (apoptosis) in TRPC1-knockdown ECs whereas thrombin had no effect on control or
      control siRNA-transfected ECs. To understand the basis of EC survival, we
      performed gene microarray analysis using ECs. Thrombin stimulation increased only
      a set of NF-kappaB-regulated genes 3- to 14-fold over basal levels in ECs.
      Expression of the antiapoptotic gene A20 was the highest among these upregulated
      genes. Like TRPC1 knockdown, thrombin induced apoptosis in A20-knockdown ECs. To
      address the importance of Ca(2+) influx signal, we measured thrombin-induced A20
      expression in control and TRPC1-knockdown ECs. Thrombin-induced p65/RelA binding
      to A20 promoter-specific NF-kappaB sequence and A20 protein expression were
      suppressed in TRPC1-knockdown ECs compared with control ECs. Furthermore, in
      TRPC1-knockdown ECs, thrombin induced the expression of proapoptotic proteins
      caspase-3 and BAX. Importantly, thrombin-induced apoptosis in TRPC1-knockdown ECs
      was prevented by adenovirus-mediated expression of A20. These results suggest
      that Ca(2+) influx via TRPC channels plays a critical role in the mechanism of
      cell survival signaling through A20 expression in ECs.

PMID- 20032511
TI  - Thrombin induces endothelial arginase through AP-1 activation.
AB  - Arterial thrombosis is a common disease leading to severe ischemia beyond the
      obstructing thrombus. Additionally, endothelial dysfunction at the site of
      thrombosis can be rescued by l-arginine supplementation or arginase blockade in
      several animal models. Exposure of rat aortic endothelial cells (RAECs) to
      thrombin upregulates arginase I mRNA and protein levels. In this study, we
      further investigated the molecular mechanism of thrombin-induced arginase changes
      in endothelial cells. Thrombin strikingly increased arginase I promoter and
      enzyme activity in primary cultured RAECs. Using different deletion and point
      mutations of the promoter, we demonstrated that the activating protein-1 (AP-1)
      consensus site located at -3,157 bp in the arginase I promoter was a thrombin
      responsive element. Electrophoretic mobility shift assay and chromatin
      immunoprecipitation assay further confirmed that upon thrombin stimulation, c-Jun
      and activating transcription factor-2 (ATF-2) bound to the AP-1 site, which
      initiated the transactivation. Moreover, loss-of-function studies using small
      interfering RNA confirmed that recruitment of these two transcription factors to
      the AP-1 site was required for thrombin-induced arginase upregulation. In the
      course of defining the signaling pathway leading to the activation of AP-1 by
      thrombin, we found thrombin-induced phosphorylation of stress-activated protein
      kinase/c-Jun-NH(2)-terminal kinase (SAPK/JNK or JNK1/2/3) and p38 mitogen
      activated protein kinase, which were followed by the phosphorylation of both c
      Jun and ATF-2. These findings reveal the basis for thrombin induction of
      endothelial arginase I and indicate that arginase inhibition may be an attractive
      therapeutic alternative in the setting of arterial thrombosis and its associated
      endothelial dysfunction.

PMID- 20032514
TI  - Little caves ameliorate hepatic insulin signaling. Focus on "caveolin gene
      transfer improves glucose metabolism in diabetic mice".

PMID- 20032513
TI  - Tumor protein D52 expression and Ca2+-dependent phosphorylation modulates
      lysosomal membrane protein trafficking to the plasma membrane.
AB  - Tumor protein D52 (also known as CRHSP-28) is highly expressed in multiple
      cancers and tumor-derived cell lines; however, it is normally abundant in
      secretory epithelia throughout the digestive system, where it has been implicated
      in Ca(2+)-dependent digestive enzyme secretion (41). Here we demonstrate, using
      site-specific mutations, that Ca(2+)-sensitive phosphorylation at serine 136
      modulates the accumulation of D52 at the plasma membrane within 2 min of cell
      stimulation. When expressed in Chinese hamster ovary CHO-K1 cells, D52
      colocalized with adaptor protein AP-3, Rab27A, vesicle-associated membrane
      protein VAMP7, and lysosomal-associated membrane protein LAMP1, all of which are
      present in lysosome-like secretory organelles. Overexpression of D52 resulted in
      a marked accumulation of LAMP1 on the plasma membrane that was further enhanced
      following elevation of cellular Ca(2+). Strikingly, mutation of serine 136 to
      alanine abolished the Ca(2+)-stimulated accumulation of LAMP1 at the plasma
      membrane whereas phosphomimetic mutants constitutively induced LAMP1 plasma
      membrane accumulation independent of elevated Ca(2+). Identical results were
      obtained for endogenous D52 in normal rat kidney and HeLA cells, where both LAMP1
      and D52 rapidly accumulated on the plasma membrane in response to elevated
      cellular Ca(2+). Finally, D52 induced the uptake of LAMP1 antibodies from the
      cell surface in accordance with both the level of D52 expression and
      phosphorylation at serine 136 demonstrating that D52 altered the plasma membrane
      recycling of LAMP1-associated secretory vesicles. These findings implicate both
      D52 expression and Ca(2+)-dependent phosphorylation at serine 136 in lysosomal
      membrane trafficking to and from the plasma membrane providing a novel Ca(2+)
      sensitive pathway modulating the lysosome-like secretory pathway.

PMID- 20032512
TI  - CYP1B1 and endothelial nitric oxide synthase combine to sustain proangiogenic
      functions of endothelial cells under hyperoxic stress.
AB  - We have recently shown that deletion of constitutively expressed CYP1B1 is
      associated with attenuation of retinal endothelial cell (EC) capillary
      morphogenesis (CM) in vitro and angiogenesis in vivo. This was largely caused by
      increased intracellular oxidative stress and increased production of
      thrombospondin-2, an endogenous inhibitor of angiogenesis. Here, we demonstrate
      that endothelium nitric oxide synthase (eNOS) expression is dramatically
      decreased in the ECs prepared from retina, lung, heart, and aorta of CYP1B1
      deficient (CYP1B1(-/-)) mice compared with wild-type (CYP1B1(+/+)) mice. The eNOS
      expression was also decreased in retinal vasculature of CYP1B1(-/-) mice.
      Inhibition of eNOS activity in cultured CYP1B1(+/+) retinal ECs blocked CM and
      was concomitant with increased oxidative stress, like in CYP1B1(-/-) retinal ECs.
      In addition, expression of eNOS in CYP1B1(-/-) retinal ECs or their incubation
      with a nitric oxide (NO) donor enhanced NO levels, lowered oxidative stress, and
      improved cell migration and CM. Inhibition of CYP1B1 activity in the CYP1B1(+/+)
      retinal ECs resulted in reduced NO levels and attenuation of CM. In contrast,
      expression of CYP1B1 increased NO levels and enhanced CM of CYP1B1(-/-) retinal
      ECs. Furthermore, attenuation of CYP1B1 expression with small interfering RNA
      proportionally lowered eNOS expression and NO levels in wild-type cells.
      Together, our results link CYP1B1 metabolism in retinal ECs with sustained eNOS
      activity and NO synthesis and/or bioavailability and low oxidative stress and
      thrombospondin-2 expression. Thus CYP1B1 and eNOS cooperate in different ways to
      lower oxidative stress and thereby to promote CM in vitro and angiogenesis in
      vivo.

PMID- 20032516
TI  - The silver jubilee: Journal of Child Neurology turns 25.

PMID- 20032515
TI  - Retinal metabolic state of the proline-23-histidine rat model of retinitis
      pigmentosa.
AB  - We determined the metabolic changes that precede cell death in the dystrophic
      proline-23-histidine (P23H) line 3 (P23H-3) rat retina compared with the normal
      Sprague-Dawley (SD) rat retina. Metabolite levels and metabolic enzymes were
      analyzed early in development and during the early stages of degeneration in the
      P23H-3 retina. Control and degenerating retinas showed an age-dependent change in
      metabolite levels and enzymatic activity, particularly around the time when
      phototransduction was activated. However, lactate dehydrogenase (LDH) activity
      was significantly higher in P23H-3 than SD retina before the onset of
      photoreceptor death. The creatine/phosphocreatine system did not contribute to
      the increase in ATP, because phosphocreatine levels, creatine kinase, and
      expression of the creatine transporter remained constant. However, Na(+)-K(+)
      ATPase and Mg(2+)-Ca(2+)-ATPase activities were increased in the developing P23H
      3 retina. Therefore, photoreceptor apoptosis in the P23H-3 retina occurs in an
      environment of increased LDH, ATPase activity, and higher-than-normal ATP levels.
      We tested the effect of metabolic challenge to the retina by inhibiting
      monocarboxylate transport with alpha-cyano-4-hydroxycinnamic acid or systemically
      administering the phosphodiesterase inhibitor sildenafil. Secondary to
      monocarboxylate transport inhibition, the P23H-3 retina did not demonstrate
      alterations in metabolic activity. However, administration of sildenafil
      significantly reduced LDH activity in the P23H-3 retina and increased the number
      of terminal deoxynucleotidyl transferase biotin-dUPT nick end-labeled
      photoreceptor cells. Photoreceptor cells with a rhodopsin mutation display an
      increase in apoptotic markers secondary to inhibition of a phototransduction
      enzyme (phosphodiesterase), suggesting increased susceptibility to altered cation
      entry.

PMID- 20032517
TI  - Toward a narrower, more pragmatic view of developmental dyspraxia.
AB  - Apraxia traditionally refers to impaired ability to carry out skilled movements
      in the absence of fundamental sensorimotor, language, or general cognitive
      impairment sufficient to preclude them. The child neurology literature includes a
      much broader and varied usage of the term developmental dyspraxia. It has been
      used to describe a wide range of motor symptoms, including clumsiness and general
      coordination difficulties, in various developmental disorders (including autistic
      spectrum disorders, developmental language disorders, and perinatal stroke). We
      argue for the need to restrict use of the term developmental dyspraxia to
      describe impaired performance of skilled gestures, recognizing that, unlike
      acquired adult-onset apraxia, coexisting sensory and motor problems can also be
      present.

PMID- 20032518
TI  - Central system nervous tuberculosis in infants.
AB  - The lack of specific symptoms and signs in patients with tuberculous meningitis
      makes early diagnosis difficult. In this report, we reviewed the clinical
      features and laboratory findings of 6 infants with central system nervous
      tuberculosis during a 10-year period. One of the patients had multifocal
      tuberculosis. The mean time to the diagnosis was 32 +/- 13.4 days. A contact
      source was identified in only 2 patients. All 6 patients had abnormal
      cerebrospinal fluid findings, less than 500 cells/microL with lymphocytic
      predominance. Computerized tomography (CT) and/or magnetic resonance imaging
      (MRI) revealed hydrocephalus with basal enhancement in 2 patients. One patient
      developed pontocerebellar and pituitary tuberculomas, which were responsible for
      compression and diabetes insipidus, 1 year after antituberculous treatment. These
      localizations are very rare. On the follow-up, 3 patients had hypoacousia and
      only 1 had severe sequelae, despite a diagnostic delay.

PMID- 20032519
TI  - Correspondence on ''deterioration in cognitive function in children with benign
      epilepsy of childhood with central temporal spikes treated with sulthiame''.

PMID- 20032520
TI  - Correspondence on ''determination of basal metabolic rate and body composition
      with bioelectrical impedance method in children with cerebral palsy''.

PMID- 20032521
TI  - Increasing recognition of cases with male Aicardi syndrome.

PMID- 20032523
TI  - The prevalence of osteoporosis in patients with severe hip and knee
      osteoarthritis awaiting joint arthroplasty.
AB  - BACKGROUND: the presence of osteoporosis in patients with hip and knee
      osteoarthritis (OA) has important implications for understanding disease
      progression and providing optimal surgical and medical management. OBJECTIVE: to
      determine the prevalence of osteoporosis among patients with osteoarthritis
      awaiting total knee arthroplasty or total hip arthroplasty aged between 65 and 80
      years. DESIGN: cross-sectional observational study. SETTING: tertiary referral
      centre in Newcastle upon Tyne, UK. SUBJECTS: patients with osteoarthritis
      awaiting total knee hip arthroplasty aged between 65 and 80 years. METHODS:
      lumbar spine, bilateral femoral and forearm bone mineral density (BMD)
      measurements were obtained using dual-energy X-ray absorptiometry. RESULTS: the
      cohort consisted of 199 patients with a mean age of 72 years (SD 4), and 113
      (57%) were women. The overall rate of osteoporosis at any site was 23% (46/199)
      and a further 43% (85/199) of patients would have been classified as osteopaenic
      according to World Health Organization criteria. Osteoporosis was more commonly
      detected in the forearm (14%) than the lumbar spine (8.5%) and proximal femur of
      the index side (8.2%). CONCLUSIONS: in summary, a significant proportion of
      patients with end-stage OA have osteoporosis but this diagnosis may be missed
      unless BMD measurements are performed at sites distant from joints affected by
      OA.

PMID- 20032524
TI  - Treatment of idiopathic scoliosis exceeding 100 degrees - comparison of different
      surgical techniques.
AB  - BACKGROUND: The treatment of scoliosis exceeding 100 degrees remains a challenge.
      Anterior fusion only may lead to low correction and screw plowing, posterior
      fusion only may cause the cranckshaft phenomenon in skeletally immature patients.
      Two-stage surgery is advocated, comprising anterior release and posterior fusion.
      MATERIAL AND METHODS: The aim of the paper is to compare treatment outcomes in
      patients with a >100% primary curve treated between 1984 - 2004 with one of the
      following techniques: halo-femoral traction with posterior fusion (Group I; n=124
      patients), anterior release with halo-femoral traction and posterior fusion
      (Group II; n=32), single stage anterior release and posterior fusion (Group III;
      n=20), and posterior fusion only (Group IV; n=19). Correction and loss of
      correction were assessed radiologically. Additional surgical procedures and the
      presence of complications were also recorded. The fusion techniques were
      compared. Mean post-operative follow-up duration was 3.9 years, ranging from 2 to
      15.3 years. RESULTS: Correction was highest in Group II and Group III (52.7% and
      51.7%, respectively); vs. Group I and Group IV (45.8% and 38.7%, respectively).
      The loss of correction at final follow-up was lowest in Group II and Group III
      (2% and 3.3%), and highest in Group I and Group IV (6.4% and 15.6%, p<0.05). In
      all groups, the use of derotational instrumentation increased correction (59.7% C
      D vs. 37% Wisconsin vs. 24.5% Harrington-Luque) and decreased loss of correction
      (4% C-D vs. 5% Harrington-Luque vs. 28% Wisconsin). Rates of neurological
      complications were similar in all groups; no persistent deficits were noted.
      CONCLUSIONS: Anterior release with halo traction and posterior fusion is the
      optimal treatment of severe scoliosis. If halo traction is contraindicated,
      single stage anterior release and posterior fusion should be performed.
      Contemporary instrumentation techniques result in higher correction rates and
      better curve stability.

PMID- 20032525
TI  - Retrospective study of two-stage surgery in the treatment of scoliosis exceeding
      100 degrees - assessment including spinal balance evaluation.
AB  - BACKGROUND: Scoliosis exceeding 100 degrees remains an important problem in
      spinal orthopaedics. The choice of an optimal surgical technique is crucial, not
      only because of the degree of correction needed, but also because of the need to
      minimize the number of complications and avoid imbalance after surgery. The aim
      of this work is to analyse the outcomes of a two-stage surgical regimen for
      scoliosis exceeding 100 degrees consisting of anterior release, cranio-femoral
      traction, and posterior fusion with derotational instrumentation. MATERIAL AND
      METHODS: Twelve patients with thoracic scoliosis (7 females and 5 males) were
      assessed retrospectively. The mean curve angle before surgery was 129 degrees.
      All patients underwent a two-stage procedure consisting of anterior release
      followed by 10-14 days of cranio-femoral traction and posterior fusion with
      derotational instrumentation. Mean age at surgery was 19 years. The mean follow
      up period was 5 years. Radiological evaluation was based on postero-anterior and
      lateral radiographs. RESULTS: Mean curve correction was 44% and this result was
      stable during the follow-up period. Thoracic kyphosis did not change
      significantly after treatment, remaining at 61 degrees on average. Coronal
      decompensation was noted in 4 patients before surgery and one of the four after
      treatment. The Th1-midline distance improved significantly, as did the Th12-L2
      angle on lateral radiographs. There were no neurological complications.
      CONCLUSION: Two-stage treatment of very severe scoliosis enables stable
      correction with some improvement of spinal balance in both the coronal and
      sagittal plane.

PMID- 20032526
TI  - Does instrumentation removal cause curve progression in patients with adolescent
      idiopathic scoliosis?
AB  - Adolescent idiopathic scoliosis (AIS) is usually instrumented using a posterior
      approach. Hardware removal may be performed for specific clinical reasons. Little
      data is available on whether removal influences curve magnitude. The aim of the
      paper is to evaluate the impact of instrumentation removal on curve progression,
      and the safety and efficacy of the procedure. We analyzed 59 patients who
      underwent instrumentation removal. Curve types, reasons for removal, period
      between procedures, and Cobb angles: at baseline, immediately after correction,
      after removal and in follow-up were evaluated. Clinical symptoms were also
      assessed. The mean follow-up period after instrumentation removal was 2.2 years
      (1-5 years). The mean age at primary surgery was 14.5 years (12-25 years) and the
      mean Cobb angle after surgery was 24.9 degrees in the thoracic spine, and 17.5
      degrees in the lumbar spine. The period between procedures was 46.6 months (11
      192 months). The reasons for removal were: fistula (38.9%), pain (35.6%), rib
      hump removal (13.6%), and hardware failure (11.9%). At the final follow-up, mean
      thoracic curve was 35.4 degrees and lumbar curve was 26.2 degrees , corresponding
      to 13.3% and 17.5% curve progression after removal, respectively. Patients with
      infection had the highest loss of correction (21%). In symptomatic patients, pain
      subsided in 70% of the cases. In cases of hardware removal > 2 years after
      fusion, loss of correction was lower than in the < 2 years group. The course of
      surgery was relatively uneventful.

PMID- 20032528
TI  - Comparison of results of Cotrel-Dubousset instrumentation with partial rib
      resection at curve apex and without resection treatment based on the Scoliosis
      Research Society questionnaire.
AB  - OBJECTIVE: To compare subjective treatment outcomes in patients with idiopathic
      scoliosis who underwent Cotrel-Dubousset instrumentation with rib resection at
      the curve apex and in patients who did not undergo rib resection at the same time
      as scoliosis correction. MATERIAL AND METHODS: Treatment outcomes were assessed
      with the Scoliosis Research Society questionnaire. The study group included 68
      patients who had undergone scoliosis correction with Cotrel-Dubousset
      instrumentation without concurrent rib resection and 60 patients who underwent
      rib resection during scoliosis correction surgery using fragments of the resected
      ribs for posterior fusion. Mean time since surgery was 4 years 4 months in the
      first group, and 2 years and 6 months in the second. Mean age of patients at the
      time of Cotrel-Dubousset instrumentation surgery was 14 years 8 months in the
      first group and 15 years 6 months in the second. RESULTS: There was a
      statistically significant difference between the two groups (in favour of the
      group with the rib resection) in the mean number of points per question in the
      overall score and the satisfaction with surgery, pain, general self-image, and
      post-operative function domain scores. CONCLUSION: In the light of the SRS
      questionnaire, reduction of rib curve height concurrent with Cotrel-Dubousset
      instrumentation increased the degree of treatment satisfaction and improved
      patients' self-esteem without increasing back or chest pain.

PMID- 20032527
TI  - Assessment of respiratory function in girls with scoliosis after thoracoplasty.
AB  - BACKGROUND: The aim of the study was to assess pulmonary function in patients
      after spinal fusion combined with thoracoplasty in comparison with subjects in
      whom thoracoplasty was not performed, but who underwent intensive rehabilitation.
      MATERIAL NA DMETHODS: The study population consisted of two groups of adolescent
      girls about two years after surgical correction of scoliosis by Cotrel-Dubousset
      method. The subjects in the first group (thoracoplasty group) underwent spinal
      fusion in combination with thoracoplasty, which consisted in subperiosteal
      resection of deformed segments of six ribs on top of the rib hump. Patients in
      the second group (rehabilitation group) had no thoracoplasty, but participated in
      a 4-week rehabilitation programme based on endurance training. Pulmonary function
      was assessed in all subjects with resting spirometry. Additionally, maximal
      oxygen uptake was determined using an indirect method. RESULTS: Spirometric
      parameters at rest were significantly higher in subjects participating in the
      rehabilitation program compared to the thoracoplasty patients. VO2max values were
      similar in both groups, indicating relatively good exercise capacity.
      CONCLUSIONS: Comprehensive motor rehabilitation based on endurance training has a
      favorable influence on pulmonary function in patients after surgical correction
      of scoliosis. A rehabilitation program should be included in the management of
      patients after spinal fusion combined with thoracoplasty.

PMID- 20032529
TI  - Assessment of quality of life in patients with idiopathic scoliosis treated
      operatively.
AB  - BACKGROUND: A small percentage of patients with idiopathic scoliosis undergo
      surgery, which is only used in the case of the most extreme deformities of the
      spine and chest and progression of disease despite conservative treatment. The
      aim of this study was to assess the quality of life in patients with idiopathic
      scoliosis treated operatively and to examine the correlations between the quality
      of life and radiographic and socio-demographic indices. MATERIAL AND METHODS: wo
      independent groups of patients operated on at the Department of Pediatric
      Orthopedics of the Pomeranian Medical University in Szczecin were examined using
      a standardized SRS -22 HRQL instrument. Quality of life was assessed on three
      occasions in 35 patients from the first group. The second group included 52
      patients at least two years post-surgery. RESULTS: The assessment of physical
      fitness revealed a decrease proportional to the length of time since surgery.
      Higher pain intensity was reported by patients whose surgery took place more than
      2 years prior to the study. The analysis of mental health assessment results
      indicated a decrease proportional to the length of time since surgery. No
      statistically significant differences were found with respect to patients' self
      assessment of their body image and treatment satisfaction. CONCLUSIONS: 1.
      Operative correction of scoliosis enhances patients' self-assessment of their
      body image and contributes to a high assessment score for treatment satisfaction.
      2. No correlations were found between the overall quality of life and previous
      conservative treatment. 3. Deterioration of physical fitness, mental health
      impairment and increasing pain intensity were observed among patients residing in
      small towns and rural areas and those experiencing socioeconomic problems 4. The
      degree of scoliosis correction in the thoracic spine contributes to increasing
      life quality, especially in late assessment.

PMID- 20032530
TI  - Computed tomography-based study of age- and sex-related variation in morphology
      of the femur.
AB  - BACKGROUND: The femur has a complex shape with marked individual differences. The
      aim of our study was to investigate the anatomy of the femur in normal subjects
      using computed tomography imaging with the aim of building a digital database of
      human femoral anatomy. MATERIAL AND METHODS: We studied age- and sex-related
      variation in the shape of the femur in 169 normal subjects (80 men and 89 women)
      using Computed Tomography. Subjects were divided into three age groups (Group I:
      < 35 years; Group II: 36 - 55 years; Group III: > 56 years). Measurements were
      taken of transverse sections at 25%, 50% and 75% of femoral length. RESULTS: The
      bony surface at the transverse section at 50% of the length of the femur was
      greater in the older men (p=0.007). There were differences in the medullary canal
      surface area of the femur at the section at 50% of its length in both women and
      men (p=0.02). CONCLUSION: Our study provides a detailed characterization of the
      anatomical features of the femur of normal subjects, and can be helpful in
      modelling prosthetic implants or internal fixation devices in relation to the age
      and sex of the patients.

PMID- 20032531
TI  - Transplantation of amputated bony phalanges as a salvage thumb reconstruction
      method - a preliminary report.
AB  - BACKGROUND: Every traumatic amputation of the thumb is an indication for an
      attempt of replantation. Due to local state of the wound not every case qualifies
      for this procedure. Such patients may be offered a multi-step salvage
      reconstruction of the amputated finger; the first step consists of an emergency
      implantation of the bony phalanx under the skin of the abdominal wall. The
      osseous graft was covered with skin using a pedicled tubular flap or a "cutaneous
      pocket". The aim of this paper was to evaluate the effectiveness of this
      reconstructive method. MATERIAL AND METHODS: Over a period of four years, we
      operated on 24 patients (22 males, 2 females) aged 17 - 56 years (mean 31.3 yrs);
      trauma affected the dominant hand in 16 cases (66%); 17 patients (71%) lost their
      thumbs at the level of IP joint ; in the remaining 7 cases (29%) the amputation
      was at the level of the MCP joint. In 3 cases with concomitant amputation of the
      2nd and 3rd fingers, the grafted structure was the bony phalanx of the index
      finger. The grafted phalanx, its soft tissues pared off, was joined with the
      proximal phalanx or the 1st metacarpal bone with two K-wires and then covered
      with a pedicled tubular flap or implanted to a cutaneous pocket preformed from
      the abdominal wall. The flap and the "pocket" were cut away on average after 30.2
      days. The cutaneous plasty of the finger was performed on average after 11.3
      weeks; the sensory island was transferred according to Littler in 18 patients on
      average 22.2 weeks after the amputation. The evaluation included: osteosynthesis,
      mobility of the finger (Kapandji's test), pinch-grip strength, touch sensation
      (filament and discriminatory, temperature sensitivity), esthetics of the finger,
      and the employment status of the patients. RESULTS: Failure of losing the graft
      occurred in 3 patients (12%) and was due to an infection unresponsive to
      treatment and developing on necrotic flaps. Five patients (21%) developed
      marginal necrosis within the fragments of the cut off flaps requiring cutaneous
      plasty; an inflammation of the recipient site occurred in 5 cases (21%). 18
      patients (75%) of the patients turned up for the distant follow-up on average
      13.2 months after the accident (range 11 - 28 mths). 16 patients (89%) had good
      bone union; in 2 cases the distal part of the graft had been resorbed. All of the
      patients were able to touch the pseudo-ball of the thumb with the 5th finger. The
      strength of the pinch-grip on average reached 3.3 kG (range 1.8 - 6.2 kG), which
      equals to 55% (range 36 - 78%) of the uninjured hand. Touch sensation was
      satisfactory in 16 patients (89%) (blue filament), reduced in 2 (11%); 6 patients
      (33%) showed two-point discrimination in the range of 10 to 15 mm. The esthetical
      result of the thumb was assessed as good in 13 (72%) and satisfactory in 5
      patients (28%). Fifteen patients (83%), 9 blue collar workers and 6 farmers,
      continued with their occupations. CONCLUSION: The autograft of the amputated
      phalanx is a valuable reconstructive method for a selected group of patients.

PMID- 20032532
TI  - The use of computer tomography for preoperative planning and outcome assessment
      in surgical treatment of idiopathic scoliosis with pedicle screw based constructs
      - case presentation.
AB  - BACKGROUND: In recent years pedicle screw based constructs have been increasingly
      used in the operative management of scoliosis. The current principles of screw
      placement are based on normal anatomy and therefore may not be applicable in
      cases of severe vertebral deformity due to torsion. The aim of this study was to
      evaluate the usefulness of computer tomography (CT) in preoperative planning and
      outcome assessment in operative management of idiopathic scoliosis with severe
      internal vertebral deformity. MATERIAL AND METHODS: The study presents our own
      experiences based on analysis of diagnostic and therapeutic decision-making in
      two patients treated surgically due to Lenke type 1A idiopathic scoliosis. Due to
      extensive vertebral rotation and radiological appearance suggesting thin
      pedicles, spine CT with 3D reconstruction was performed as part of extended
      preoperative work-up in order to determine screw length and diameter, the point
      of screw introduction and angle of introduction in three planes. Vertebral
      rotation was evaluated according to the Aaro-Dahlborn method. Segments were also
      identified where pedicle screws could not be applied due to severe rotation or
      small pedicle diameter. RESULTS: Preoperative planning of screw placement enabled
      safe and accurate screw application, as confirmed by postoperative spine CT
      evidence. Satisfactory correction was achieved in both patients in the coronal
      and frontal planes. CONCLUSIONS: CT allows detailed preoperative planning of
      scoliosis surgery and identification of segments in which pedicle screws cannot
      be safely placed. This may lower the incidence of complications associated with
      inaccurate pedicle screw placement.

PMID- 20032533
TI  - Effectiveness and safety of antiretrovirals with rifampicin: crucial issues for
      high-burden countries.
AB  - Coadministration of antitubercular and antiretroviral therapy is common in high
      burden countries where tuberculosis is the commonest opportunistic infection.
      Concomitant use of rifampicin and many antiretroviral drugs is complicated by
      drug-drug interactions caused by the potent induction by rifampicin of genes
      involved in drug metabolism and transport, which could result in subtherapeutic
      antiretroviral drug concentrations. This review focuses on drug-drug interactions
      involving antiretrovirals used in resource-limited settings: the non-nucleoside
      reverse transcriptase inhibitors (NNRTIs) efavirenz or nevirapine, and ritonavir
      boosted protease inhibitors. The reduction of nevirapine concentrations with
      concomitant rifampicin is greater than with efavirenz, particularly during the
      lead-in dose period when subtherapeutic concentrations occur in the majority of
      patients. There is reassuring data on the effectiveness of standard doses of
      efavirenz with concomitant rifampicin, but the largest cohort study found a
      higher risk of virological failure with nevirapine. The drug-drug interaction
      between rifampicin and ritonavir-boosted protease inhibitors is more marked than
      with the NNRTIs, and therapeutic concentrations have only been achieved with
      adjusted doses of lopinavir/ritonavir or with saquinavir/ritonavir (400/400 mg
      every 12 h). The major barrier to using adjusted dose protease inhibitors with
      rifampicin is the high rates of hepatotoxicity seen in healthy volunteers. The
      alternative strategy followed in resource-rich settings is to replace rifampicin
      with rifabutin, but even if the price of rifabutin were to be dramatically
      reduced it would be difficult to implement in high-burden countries where
      standardized antitubercular regimens with fixed-dose combinations are used.

PMID- 20032534
TI  - Reducing treatment duration in patients infected with hepatitis C genotype 1: any
      need for further studies?
AB  - The recommended treatment duration with pegylated interferon-alpha plus ribavirin
      for patients infected with hepatitis C virus (HCV) genotype 1 is 48 weeks.
      Interestingly, a subpopulation of genotype 1 patients experience rapid decreases
      in HCV RNA levels once treatment is initiated and attain rapid virological
      response, defined as undetectable HCV RNA at week 4 of therapy. Several studies
      have shown that these patients can be effectively treated for a 24-week period
      without any significant decreases in sustained virological response rates. The
      aim of this review was to consider the existing clinical evidence regarding the
      use of a 24-week treatment schedule among genotype 1 patients and to highlight
      the characteristics of patients most suitable for this shortened treatment
      schedule.

PMID- 20032535
TI  - Herpesviridae and novel inhibitors.
AB  - Herpesviridae comprises a large family of double-stranded DNA viruses that infect
      both animals and humans. Eight herpesviruses are known to infect humans: herpes
      simplex virus type-1 and -2, varicella zoster virus, human cytomegalovirus,
      Epstein-Barr virus, human herpesvirus 6 type-A and -B, human herpesvirus type-7
      and -8 or Kaposi's sarcoma virus. Despite the fact that the past two decades have
      been evolutionary in the development of antiviral agents, therapeutic choices are
      restricted by limited efficacy and toxicity. Viral infections remain the cause of
      significant mortality worldwide, thus indicating the high medical need for the
      introduction of novel promising compounds in the antiviral chemotherapy era. This
      review focuses on recent data regarding several novel groups of agents that have
      proved to be effective as antiherpetic drugs. The agents mentioned are those
      considered to be the most likely candidates for entering clinical trials and
      those in the process of being granted approval by the US Food and Drug
      Administration. The diversity in their molecular mechanism of action highlights
      the different perspectives currently encountered in the era of antiviral therapy.

PMID- 20032537
TI  - Increased arterial stiffness in HIV-infected children: risk factors and
      antiretroviral therapy.
AB  - BACKGROUND: Recent evidence suggests that both the HIV virus and antiretroviral
      therapy (ART) are associated with premature atherosclerosis in adults. Increased
      arterial stiffness as assessed by pulse wave velocity (PWV) has been associated
      with adverse cardiovascular outcome in adults. The relationship between HIV
      infection and treatment and arterial stiffness has not been evaluated in
      children. METHODS: We studied 83 HIV-infected children with a mean +/-sd age of
      11.0 +/-3.1 years and 59 controls aged 12.2 +/-2.8 years. Among the HIV-infected
      children, 48 were receiving ART (23 including a protease inhibitor). Arterial
      stiffness was assessed non-invasively by carotid-radial PWV. Disease severity was
      defined according to the CDC classification. RESULTS: PWV was significantly
      increased in HIV-infected children compared with controls (P<0.05). A significant
      association between age and PWV was noted in HIV-infected children but not in
      controls. HIV-infected children receiving ART had significantly increased total
      cholesterol levels and PWV compared with non-treated children (P<0.001 and
      P<0.05, respectively). CDC stage was greater in ART-treated compared with non
      treated HIV-infected children (P<0.001). No differences in other cardiovascular
      risk factors were noted in the two groups. After multivariable analysis, ART,
      systolic blood pressure, disease severity and total cholesterol remained
      independent predictors of PWV. CONCLUSIONS: HIV-infected children have increased
      arterial stiffness compared with healthy children. These changes were more
      pronounced with increasing age in HIV-infected children particularly in those who
      were receiving ART.

PMID- 20032538
TI  - Pretreatment with pegylated interferon prevents emergence of lamivudine mutants
      in lamivudine-naive patients: a pilot study.
AB  - BACKGROUND: In patients with advanced fibrosis, primary end points of long-term
      or possibly indefinite antiviral therapy are sustained inhibition of viral
      replication and avoidance of emergence of resistance. In lamivudine-treated
      patients, the strongest predictor of emergence of YMDD mutations is baseline
      hepatitis B virus (HBV) DNA viral load. We aimed to verify whether abatement of
      viraemia by a short course of pegylated interferon (PEG-IFN-alpha2a) treatment
      before lamivudine treatment could prevent the emergence of lamivudine-associated
      mutations during long-term therapy. METHODS: A total of 14 patients with
      hepatitis B e antigen (HBeAg)-negative infection (3 lamivudine-experienced and 11
      lamivudine-naive), with moderate/high viraemia (>10(6) copies/ml) and with Ishak
      stage 4-6 at liver biopsy were sequentially treated with 180 microg PEG-IFN
      alpha2a for a period long enough to reach HBV DNA levels < or =10(3) copies/ml or
      have a decrease of 3 log(10) copies/ml from baseline. Lamivudine was then added
      to PEG-IFN-alpha2a treatment for 1 month and finally continued as monotherapy for
      2 years or until viral breakthrough. RESULTS: Baseline HBV DNA (mean +/-se 2.3 x
      10(7) +/-7.2 x 10(7) copies/ml) decreased with PEG-IFN-alpha2a treatment to
      target value in mean +/-se 3.7 +/-1.3 months. None of the 11 lamivudine-naive
      patients developed genotypic resistance and were still HBV-DNA-negative after a
      mean +/-se observation period of 23 +/-2 months, whereas the three lamivudine
      experienced patients developed YMDD mutations after 6, 9 and 12 months of
      lamivudine monotherapy (P=0.003, Fisher's exact test). CONCLUSIONS: In lamivudine
      naive patients, abatement of HBV DNA<10(3) copies/ml by pretreatment with PEG-IFN
      alpha2a completely prevents the emergence of YMDD mutants after 24 months of
      lamivudine monotherapy. This sequential schedule can optimize the use of a well
      tolerated, effective and inexpensive drug, such as lamivudine, in highly viraemic
      HBV patients.

PMID- 20032539
TI  - Adipocyte differentiation, mitochondrial gene expression and fat distribution:
      differences between zidovudine and tenofovir after 6 months.
AB  - BACKGROUND: Abnormal lipid metabolism and cell oxidative mechanisms are reported
      in patients on antiretroviral treatment. We compared the expression of several
      key adipocyte genes in HIV-infected patients randomized to antiretroviral
      regimens containing zidovudine (AZT) or tenofovir disoproxil fumarate (TDF).
      METHODS: Subcutaneous fat was sampled from 32 HIV-positive treatment-naive
      patients before and 6 months after randomization to AZT/lamivudine/efavirenz
      (n=15) or TDF/emtricitabine/efavirenz (n=17) plus 15 HIV-negative matched
      controls. Expression of genes involved in adipocyte differentiation, lipid
      metabolism, mitochondrial function and glucocorticoid generation were profiled
      using real-time PCR. Lipoprotein lipase and hepatic lipase activity were
      assessed. RESULTS: Before treatment, 11beta-hydroxysteroid dehydrogenase
      expression was down-regulated compared with controls. Following 6 months
      treatment with AZT, there was a significant increase in visceral adipose tissue
      (VAT; P=0.02) and the ratio of VAT to subcutaneous adipose tissue (P=0.008), down
      regulation of cytochrome B (P=0.003) and cytochrome oxidase (COX)-3 gene
      expression (P=0.03), up-regulation of NADH dehydrogenase (P=0.008) and nuclear
      encoded COX-4 (complex IV) gene expression (P=0.012). Genes involved with
      adipocyte cortisol generation, fatty acid metabolism and the tricarboxylic acid
      cycle were up-regulated. In the TDF-treated patients, there was no significant
      change in regional body fat or mitochondrial genes compared with pretreatment
      values. Changes in the expression of genes involved with cortisol and fatty acid
      metabolism were less marked with TDF. CONCLUSIONS: Interference with the
      mitochondrial electron transport chain appears to occur early in an AZT
      containing regimen and occurs at a time when there is increased visceral fat and
      up-regulation of genes involved with adipocyte differentiation and fatty acid
      flux.

PMID- 20032540
TI  - Non-steroidal anti-inflammatory drugs increase the antiretroviral activity of
      nucleoside reverse transcriptase inhibitors in HIV type-1-infected T-lymphocytes:
      role of multidrug resistance protein 4.
AB  - BACKGROUND: The multidrug resistance proteins (MRPs) form a subfamily within the
      ATP binding cassette transporters that confer resistance to a variety of
      structurally unrelated compounds. MRP4 has been reported to transport
      antiretroviral drugs out of cells in an active process. Although the main
      therapeutic effects of non-steroidal anti-inflammatory drugs (NSAIDs) are their
      ability to inhibit cyclooxygenase activity, in recent years, some pharmacological
      effects independent of this action have been described, such as inhibition of the
      activity of MRP4. METHODS: Detection of MRP4 expression was carried out by
      Western blot analysis, immunofluorescence and flow cytometry in peripheral blood
      lymphocytes (PBLs). Cells were infected with HIV type-1(NL4.3) isolate, and
      treated with antiretroviral drugs plus different NSAIDs. Agp24 was measured by
      ELISA 3 days post-infection. Intracellular [(3)H] zidovudine (AZT) was quantified
      by a scintiller counter. Expression of different cell markers was assessed by
      flow cytometry. RESULTS: NSAIDs, as well as probenecid, were able to potentiate
      the antiretroviral effect of several nucleoside reverse transcriptase inhibitors
      (NRTIs). PBLs expressed MRP4 and treatment with ibuprofen did not affect this
      expression. However, MRP4 expression increased following phytohaemaglutinin and
      AZT treatment. This decrease of Agp24 was correlated with an increase in the
      intracellular AZT concentration. This effect was unrelated to changes on
      expression of CD4, CXCR4, cell viability or activation. Interestingly, patients
      treated with highly active antiretroviral therapy, who had a detectable viral
      load, presented a higher expression of MRP4 than those with an undetectable viral
      load. CONCLUSIONS: NSAIDs can improve the antiretroviral activity of NRTIs,
      increasing their intracellular concentration by blocking MRP4. This finding could
      have implications for success of antiviral therapy.

PMID- 20032536
TI  - Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of
      combination antiretroviral therapy: a European multicohort study.
AB  - BACKGROUND: Incidence and risk factors of HIV-associated non-Hodgkin's lymphoma
      (NHL) are not well defined in the era of combination antiretroviral therapy
      (cART). METHODS: A total of 56,305 adult HIV type-1 (HIV-1)-infected patients who
      started cART in 1 of 22 prospective studies in Europe were included. Weibull
      random effects models were used to estimate hazard ratios (HRs) for developing
      systemic NHL and included CD4(+) T-cell counts and viral load as time-updated
      variables. RESULTS: During the 212,042 person-years of follow-up, 521 patients
      were diagnosed with systemic NHL and 62 with primary brain lymphoma (PBL). The
      incidence rate of systemic NHL was 463 per 100,000 person-years not on cART and
      205 per 100,000 person-years in treated patients for a rate ratio of 0.44 (95%
      confidence interval [CI] 0.37-0.53). The corresponding incidence rates of PBL
      were 57 and 24 per 100,000 person-years (rate ratio 0.43, 95% CI 0.25-0.73).
      Suppression of HIV-1 replication on cART (HR 0.60, 95% CI 0.44-0.81, comparing <
      or =500 with 10,000-99,999 copies/ml) and increases in CD4(+) T-cell counts (HR
      0.30, 0.22-0.42, comparing > or =350 with 100-199 cells/microl) were protective;
      a history of Kaposi's sarcoma (HR 1.70, 1.08-2.68, compared to no history of
      AIDS), transmission through sex between men (HR 1.57, 1.19-2.08, compared with
      heterosexual transmission) and older age (HR 3.71, 2.37-5.80, comparing > or =50
      with 16-29 years) were risk factors for systemic NHL. CONCLUSIONS: The incidence
      rates of both systemic NHL and PBL were substantially reduced in patients on
      cART. Timely initiation of therapy is key to the prevention of NHL in the era of
      cART.

PMID- 20032542
TI  - Combined prophylactic and therapeutic intranasal vaccination against human
      papillomavirus type-16 using different adeno-associated virus serotype vectors.
AB  - BACKGROUND: Cervical cancer is the second most frequent cancer among woman
      worldwide and is considered to be caused by infection with high-risk papilloma
      viruses. Genetic immunization using recombinant adeno-associated virus (rAAV)
      vectors has shown great promise for vaccination against human papillomavirus
      (HPV) infections. METHODS: rAAV5, -8 and -9 vectors expressing an HPV16 L1/E7
      fusion gene were generated and applied intranasally for combined prophylactic and
      therapeutic vaccination of mice. RESULTS: The rAAV5 and the rAAV9 vectors showed
      efficient induction of both humoral and cellular immune responses, whereas rAAV8
      failed to immunize mice by the intranasal route. The L1-specific immune response
      evoked by expression of the L1/E7 fusion gene, however, was lower than that
      evoked by expression of the L1 antigen alone. This deficiency could be
      compensated by application of Escherichia coli heat-labile enterotoxin or
      monophsphoryl lipid as adjuvant upon vaccination with rAAV5-L1/E7. Coimmunization
      of rAAV9-L1/E7 with rAAV5-L1 or boosting of rAAV9-L1/E7 with rAAV5-L1 strongly
      increased L1-specific neutralizing antibody titres to levels above those achieved
      by vaccination with vectors expressing L1 alone. Both vectors elicited a vibrant
      cytotoxic T-lymphocyte response against L1 or E7. Nasal immunization with rAAV5
      or rAAV9 was superior to vaccination with HPV16-L1 virus-like particles (VLPs) or
      HPV16-L1/E7 CVLPs with respect to humoral and cellular immune responses.
      Vaccination with the rAAV vectors led to a significant protection of animals
      against a challenge with different HPV tumour cell lines. CONCLUSIONS: Our
      results show that rAAV5 and rAAV9 vectors are promising candidates for a non
      invasive nasal vaccination strategy.

PMID- 20032543
TI  - Optimal length of antiviral therapy in patients with hepatitis C virus genotypes
      2 and 3: a meta-analysis.
AB  - BACKGROUND: Current guidelines recommend a duration of 24 weeks of treatment with
      pegylated interferon and ribavirin for patients infected with chronic hepatitis C
      virus (HCV) genotypes 2 and 3. Several trials investigated whether shorter
      treatment duration is equally effective in achieving sustained virological
      response (SVR). Our aim was to determine the optimal length of treatment in
      patients with HCV genotypes 2 and 3. METHODS: Systematic literature identified
      eight randomized controlled trials (RCTs). Meta-analyses were carried out on SVR
      data from three studies randomized at baseline and five studies randomized at
      rapid virological response (RVR) to either 12-16 weeks or a 24-week course.
      RESULTS: Pooled SVR data were higher in standard treatment in RCTs that
      randomized at baseline, with a relative risk (RR) of 0.88 (95% confidence
      interval [CI] 0.76-1.01). The pooled proportion of SVR rates of RCTs that
      randomized at RVR were similar in the short treatment group (82%) as in the
      standard treatment (83%), with the pooled effect given by a RR of 1.00 (95% CI
      0.92-1.09). CONCLUSIONS: A shorter course (12-16 weeks) of combination therapy
      does not impair efficacy compared with a 24-week course in HCV genotypes 2 and 3
      patients who achieve an RVR. HCV patients without RVR should consider 24 weeks of
      treatment.

PMID- 20032544
TI  - Serum levels of surface large envelope proteins: prognostic markers for hepatitis
      B e antigen-negative patients with adefovir dipivoxil treatment.
AB  - BACKGROUND: The present investigation was undertaken to evaluate the prognostic
      role of pretreatment serum hepatitis B virus (HBV) surface large envelope protein
      (LHBs) levels in the curative effects after 48-week adefovir dipivoxil (ADV)
      treatment. METHODS: A total of 128 patients received ADV once daily for 48 weeks.
      Serum levels of LHBs were detected by ELISA. Real-time quantitative PCR was used
      to analyse HBV genotype and HBV DNA copies in serum. Receiver operating
      characteristic (ROC) curve analysis was performed to assess the optimal cutoff
      value of pretreatment LHBs for predicting the curative effects of ADV treatment.
      RESULTS: After ADV treatment for 48 weeks, viral response and partial response
      were 31.4% (16/51) and 29.4% (15/51), respectively, in patients from the
      hepatitis B e antigen (HBeAg)-positive group; viral response and partial response
      were 39.7% (27/68) and 39.7% (27/68), respectively, in patients from the HBeAg
      negative group. HBeAg-negative patients with high serum levels of LHBs had low
      response rates to antiviral therapy. ROC curve analysis showed that HBeAg
      negative patients with serum LHBs levels > or =3.889 microg/ml at baseline
      predicted non-response to antiviral therapy. The sensitivity was 42.5% and
      specificity was 92.86%. Among a total of 19 patients with high serum levels of
      LHBs (> or =3.889 microg/ml) at baseline, only 2 (11%) patients responded to
      antiviral therapy. There was no correlation observed between HBV genotype and
      effects of ADV treatment. CONCLUSIONS: HBeAg-negative patients with high serum
      levels of LHBs (> or =3.889 microg/ml) at baseline should not be recommended to
      receive ADV treatment.

PMID- 20032541
TI  - Susceptibility to genital herpes as a biomarker predictive of increased HIV risk:
      expansion of a murine model of microbicide safety.
AB  - BACKGROUND: A crucial gap in the development of microbicides for HIV prevention
      is the absence of models predictive of safety. Previous studies have demonstrated
      an increased susceptibility to genital herpes in mice following repeated
      applications of nonoxynol-9 (N-9). This study was designed to explore the
      underlying mechanisms, focusing on the effects that N-9 has on genital tract
      epithelium and to apply this expanded model to evaluate the safety of
      microbicides that have been advanced to clinical trials. METHODS: Mice were
      treated intravaginally with formulated 3.5% N-9, 1% tenofovir, 0.5% or 2% PRO
      2000, hydroxyethylcellulose (HEC) placebo or no treatment and the effect on
      herpes simplex virus 2 (HSV-2) susceptibility, epithelial cell architecture,
      junctional proteins and inflammation were assessed. RESULTS: Mice treated with
      seven daily doses of N-9, but not tenofovir, PRO 2000 or HEC, were significantly
      more susceptible to challenge with low doses of HSV-2; confocal microscopy
      demonstrated increased numbers of viral particles deep within the genital tract.
      N-9 disrupted the epithelium with loss of tight and adherens junctional proteins.
      By contrast, the epithelium was relatively preserved following tenofovir, PRO
      2000 and HEC exposure. Additionally, N-9, but not the other microbicides,
      triggered a significant inflammatory response relative to untreated mice.
      CONCLUSIONS: These findings indicate that disruption of the epithelium
      contributes to increased HSV-2 susceptibility and might provide a biomarker
      predictive of increased risk for HIV acquisition. The results are consistent with
      the safety outcomes of the recently completed Phase IIb clinical trial with 0.5%
      PRO 2000 gel, and predict that tenofovir gel will not adversely affect the
      genital tract.

PMID- 20032545
TI  - Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance
      than genotype C.
AB  - BACKGROUND: Hepatitis B virus (HBV) genotype B and C seem not to affect the
      therapeutic response to lamivudine (3TC). Whether a given genotype has an earlier
      emergence of 3TC resistance remains unclear. We thus conducted this study to
      elucidate the association of HBV genotype with the emergence of 3TC-resistant
      strains in Taiwanese patients. METHODS: Forty chronic hepatitis B patients who
      developed resistance after 3TC therapy were retrospectively enrolled. HBV
      genotype, serum alanine aminotransferase (ALT) and HBV DNA levels were determined
      at baseline. The presence of 3TC-resistant mutations was confirmed by direct
      sequencing whenever biochemical breakthrough developed. RESULTS: The distribution
      of HBV genotype B and C in 40 patients receiving 3TC therapy were 60% and 40%,
      respectively. The mean interval to detect 3TC-resistant strain was 19.6 +/-1.7
      months. By using multivariate analysis, HBV genotype B and higher pre-treatment
      HBV DNA level were independently associated with earlier detection of 3TC
      resistant strains. In addition, genotype B was significantly associated with
      development of 3TC resistance within the first 12 months of 3TC therapy compared
      with genotype C (odds ratio 8.27; P=0.004). CONCLUSIONS: Compared with HBV
      genotype C, genotype B appears to have an earlier biochemical resistance to 3TC
      than genotype C. Therefore, more frequent monitoring of viral load or genotypical
      resistance might be needed for patients with HBV genotype B infection receiving
      3TC therapy, especially during the first year.

PMID- 20032546
TI  - A randomized controlled trial of pegylated interferon-alpha2a plus adefovir
      dipivoxil for hepatitis B e antigen-negative chronic hepatitis B.
AB  - BACKGROUND: Pegylated interferon (PEG-IFN)-alpha monotherapy is the current
      standard of care for short-term antiviral treatment of hepatitis B e antigen
      (HBeAg)-negative chronic hepatitis B (CHB). We aimed to assess the safety and
      efficacy of PEG-IFN-alpha plus adefovir dipivoxil (ADV) versus PEG-IFN-alpha
      monotherapy for compensated HBeAg-negative CHB. METHODS: A multicentre randomized
      controlled trial was performed in eight outpatient hepatology/infectious disease
      clinics in central Italy. A total of 60 patients (67% male and median age 48
      years) with biopsy-proven HBeAg-negative compensated CHB (mean alanine
      aminotranferase [ALT] levels 3.3 +/-3x the upper normal limit and serum hepatitis
      B virus [HBV] DNA 5.8 +/-0.9 log(10) IU/ml) were randomized at baseline to
      receive PEG-IFN-alpha2a 180 microg/week plus ADV 10 mg/day or PEG-IFN-alpha2a
      monotherapy for 48 weeks. Post-treatment follow-up was for 24 additional weeks.
      The primary end point was sustained HBV DNA suppression defined as serum HBV
      DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up. The secondary end
      point was ALT normalization at the end of follow-up. RESULTS: At week 48, HBV DNA
      was undetectable in 20/30 (67%) in the combination group versus 11/30 (37%)
      patients in the monotherapy group (P=0.02). ALT normalization was achieved in
      17/30 (57%) versus 10/30 (30%) patients, respectively (P=0.03). At week 72,
      sustained virological response was achieved in 7/30 (23.3%) in the combination
      group versus 6/30 (20%) patients in the monotherapy group (P=0.75); 5 (16%)
      patients in each group dropped out because of adverse events or non-compliance.
      CONCLUSIONS: In HBeAg-negative CHB, combination PEG-IFN-alpha2a plus ADV for 48
      weeks is safe and resulted in greater on-treatment efficacy than PEG-IFN-alpha2a
      monotherapy. No difference in sustained virological and biochemical response
      rates were observed between the two treatment regimens.

PMID- 20032547
TI  - Evaluation of minority populations of HIV type-1 with K103N and M184V drug
      resistance mutations among children in Argentina.
AB  - BACKGROUND: The aim of this study was to describe the frequency of minority
      populations of viruses carrying mutations K103N and M184V in drug-naive HIV type
      1 (HIV-1)-infected children, and to further evaluate their effect on the
      selection of drug-resistant viruses within highly active antiretroviral therapy
      (HAART). METHODS: Newly diagnosed vertically HIV-1-infected children were
      evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug
      resistance analysis. Standard genotypic sequencing and sequence-selective real
      time PCR (SPCR) to quantify minority viral populations were used. RESULTS: From
      December 2004 to July 2006, we included 35 children who were studied at baseline
      and during their first HAART regimen (follow-up median time 29.4 months). Of
      them, 82.9% were infected with intersubtype B/F recombinant variants. At
      baseline, all children had a drug-susceptible viral population that was studied
      by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11
      had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N
      minority populations were found. Once under HAART, children who had 2-10% of
      M184V at baseline further selected it in percentages >20% in less time than those
      with -0.1-0.6% or without minority populations (P=0.01). CONCLUSIONS: It was
      shown that having 2-10% of M184V at baseline enhanced its selection in high
      percentages in a short time after HAART initiation. Further research regarding
      the presence of minority quasispecies before initiation of HAART in large
      paediatric populations should be undertaken to evaluate their clinical effect
      during HAART.

PMID- 20032548
TI  - Influence of genotype on hepatitis B surface antigen kinetics in hepatitis B e
      antigen-negative patients treated with pegylated interferon-alpha2a.
AB  - BACKGROUND: The aim of this study was to assess the influence of hepatitis B
      virus (HBV) genotypes on serum hepatitis B surface antigen (HBsAg) kinetics in
      hepatitis B e antigen (HBeAg)-negative patients treated with pegylated interferon
      alpha2a (PEG-IFN-alpha2a). METHODS: A total of 48 consecutive patients treated
      with PEG-IFN-alpha2a (180 microg/week) for 48 weeks were assessed. HBV genotype
      was determined. Serum HBV DNA and HBsAg were assessed at baseline, during
      treatment (weeks 12, 24 and 48) and during follow-up (weeks 72 and 96). RESULTS:
      The distribution of HBV genotype was A 27%, B 17%, C 12%, D 29% and E 14%. Mean
      +/-sd pretreatment serum HBV DNA (6.9 +/-1.5 log(10) copies/ml) was not different
      between genotypes and decreased under treatment in all genotypes without
      significant difference. Mean +/-sd pretreatment serum HBsAg (3.6 +/-0.6 log(10)
      IU/ml) was significantly different between genotypes (P<0.001), with high levels
      in genotypes A and C, intermediate levels in genotypes D and E, and low levels in
      genotype B (4.0 +/-0.3, 4.1 +/-0.7, 3.6 +/-0.5, 3.6 +/-0.4 and 2.7 +/-0.6 log(10)
      IU/ml, respectively). Serum HBsAg decreased under treatment in all genotypes with
      a significant difference. At the end of treatment, mean +/-sd decrease was high
      in genotype A, intermediate in genotypes B and D, and low in genotypes C and E
      (1.3 +/-1.6, 0.7 +/-0.7, 0.6 +/-0.9, 0.4 +/-1.0 and 0.4 +/-0.9 log(10) IU/ml,
      respectively; P<0.001). During follow-up, serum HBsAg continued to decrease in
      genotypes A and D, whereas rebound was observed in genotypes B, C and E.
      CONCLUSIONS: HBV genotype has a strong influence on serum HBsAg kinetics during
      PEG-IFN-alpha2a therapy in HBeAg-negative patients.

PMID- 20032549
TI  - Initial evaluation of the Roche COBAS TaqMan HIV-1 v2.0 assay for determining
      viral load in HIV-infected individuals.
AB  - BACKGROUND: HIV type-1 (HIV-1) genetic diversity poses a challenge for the
      development of diagnostic tests based on nucleic acid amplification, which can be
      overcome, at least in part, by targeting multiple genomic regions. The new Roche
      Diagnostics COBAS TaqMan (CTM) HIV-1 v2.0 assay uses multiplex real-time PCR
      detection of sequences in the long terminal repeat and gag regions within the HIV
      1 genome. METHODS: We conducted initial comparative testing of HIV-1 viral load
      values in plasma samples from HIV-1-infected individuals using the Abbott
      RealTime HIV-1 (Abbott RT HIV-1), and the Roche CTM v1.0 and CTM v2.0 real-time
      PCR amplification systems, with a particular focus on patients previously
      undetectable or underestimated with the CTM v1.0 assay. RESULTS: The new Roche
      CTM v2.0 assay showed excellent agreement with the other two assays over a wide
      dynamic range (r=0.9685). The assay also allowed accurate determination of viral
      load levels in individuals infected with HIV-1 isolates that were found falsely
      negative or underestimated with the Roche CTM v1.0 assay because of mutations
      within the gag region. CONCLUSIONS: The reliability and accuracy of the CTM v2.0
      assay is similar to the Abbott RT HIV-1 assay. The implementation of a multiplex
      real-time PCR approach in the CTM v2.0 is a significant improvement in viral load
      testing in comparison with the CTM v1.0 assay.

PMID- 20032550
TI  - Key data from the 11th International Workshop on Adverse Drug Reactions and Co
      Morbidities in HIV.
AB  - The effectiveness of current antiretroviral therapies has led to more patients
      receiving long-term therapy, and increasing numbers of older patients. The
      complex interactions between HIV infection, ageing, comorbid conditions and drug
      related toxicities, and their combined effects on patient health and quality of
      life, were the subject of the 11th International Workshop on Adverse Drug
      Reactions and Co-Morbidities in HIV. Key topics included the metabolic effects of
      antiretroviral agents, cardiovascular disease, bone metabolism and age-related
      changes in disease and response to drug therapy. Data presented at the meeting
      reflect the growing recognition of common pathways that contribute to progression
      of mutiple types of disease and adverse drug reactions.

PMID- 20032551
TI  - Carbon nanotube surface modification with polyelectrolyte brushes endowed with
      quantum dots and metal oxide nanoparticles through in situ synthesis.
AB  - Carbon nanotubes (CNTs) have been successfully coated with a covalently bonded
      polymer brush of negatively charged poly(3-sulfopropylamino methacrylate) (PSPM)
      by in situ polymerization employing atomic transfer radical polymerization (ATRP)
      from initiating silanes attached to the CNTs before the polymerization. The CNT
      bonded brush forms a polymer layer or shell-like structure around the CNTs and
      provides colloidal stabilization for the CNTs in aqueous media. In situ syntheses
      of nanocrystalline CdS and magnetic iron oxide in the polymer brushes lead to the
      formation of hybrid nanocomposites consisting of nanoparticle-containing PSPM
      coated CNTs that remain readily dispersible and stable in aqueous media. The
      hybrid nanostructures are synthesized by ion exchange with the cations of the
      sulfonate groups of the PSPM followed by precipitation and were followed by
      stepwise zeta potential measurements and TEM. Such structures could have
      applications in the design of more complex structures and devices. The general
      synthetic scheme can be extended to include other nanoparticles as brush cargo to
      broaden the utility or functionality of the CNTs. TEM data shows nanocrystalline
      CdS in the range of 5-8 nm embedded in the PSPM brush and nanocrystalline iron
      oxide with a size between 2 and 4 nm, with the former consistent with UV-vis
      spectroscopy and fluorescence measurements.

PMID- 20032552
TI  - 100 nm scale low-noise sensors based on aligned carbon nanotube networks:
      overcoming the fundamental limitation of network-based sensors.
AB  - Nanoscale sensors based on single-walled carbon nanotube (SWNT) networks have
      been considered impractical due to several fundamental limitations such as a poor
      sensitivity and small signal-to-noise ratio. Herein, we present a strategy to
      overcome these fundamental problems and build highly-sensitive low-noise
      nanoscale sensors simply by controlling the structure of the SWNT networks. In
      this strategy, we prepared nanoscale width channels based on aligned SWNT
      networks using a directed assembly strategy. Significantly, the aligned network
      based sensors with narrower channels exhibited even better signal-to-noise ratio
      than those with wider channels, which is opposite to conventional random network
      based sensors. As a proof of concept, we demonstrated 100 nm scale low-noise
      sensors to detect mercury ions with the detection limit of approximately 1 pM,
      which is superior to any state-of-the-art portable detection system and is below
      the allowable limit of mercury ions in drinking water set by most government
      environmental protection agencies. This is the first demonstration of 100 nm
      scale low-noise sensors based on SWNT networks. Considering the increased
      interests in high-density sensor arrays for healthcare and environmental
      protection, our strategy should have a significant impact on various industrial
      applications.

PMID- 20032553
TI  - Thermophysical properties of hydrogenated vanadium-doped magnesium porous
      nanostructures.
AB  - Vanadium-doped magnesium nanostructures are fabricated by an oblique angle co
      deposition method and hydrogenated/dehydrogenated for 21 cycles. The effective
      thermal conductivity and density of the MgH2 nanostructures is measured by using
      a photothermal system. A multilayer physical model is used to fit the
      experimental data. Our results show that the effective thermal conductivity of
      the hydrogenated V-doped Mg nanostructures is in the range of 1.16-2.40 W m(-1)
      K(-1) and the density falls in the range of 878-1320 kg m(-3). The measured
      density agrees well with the estimation from electron micrograph observation.
      Variation in the measurements indicates strong nonuniformity of the sample
      structure and thickness. Based on the measured density and effective thermal
      conductivity, the thermal conductivity of bulk V-doped Mg hydrides is also
      evaluated using Maxwell's correlation.

PMID- 20032554
TI  - The preparation of magnetically guided lipid based nanoemulsions using self
      emulsifying technology.
AB  - This paper reports an easy and highly reproducible preparation route, using self
      emulsifying technology, for an orally administered high quality magnetically
      responsive drug delivery system. Hydrophobic iron oxide nanoparticles of about 5
      nm in diameter were prepared and incorporated into the lipid core of the produced
      oil droplets of a self-nanoemulsifying drug delivery system (MagC(18)/SNEDDS).
      The produced nanoemulsion exhibits colloidal stability at high ionic strengths
      and temperatures. The observed value of the saturation magnetization at 2 K is
      approximately 4.1 emu g(-1). The nanoemulsion displayed the magnetic properties
      of a non-interacting assembly of superparamagnetic particles and a low blocking
      temperature. Moreover the effect of MagC(18)/SNEDDS on biological systems in
      vitro was investigated in rodent fibroblasts (3T3 cells). The cytotoxicity
      studies show that none of the formulations tested affected cell activity
      significantly over the 24 h incubation. Such systems might have a potential use
      for oral delivery of poorly soluble compounds by extending the residence time of
      the formulation in the small intestine resulting in increased drug absorption
      values.

PMID- 20032555
TI  - Deterministic assembly of channeling cracks as a tool for nanofabrication.
AB  - To address the necessity for a predictive computational tool for layout design in
      crack lithography, a tool for nanowire fabrication, a computational study is
      carried out using finite element analysis, where crack-free edge and crack-crack
      interactions are studied for various material combinations. While the first
      scenario addresses the ability to induce a controlled curvature in a nanowire,
      the latter provides an estimation of the minimum distance which can be kept
      between two straight nanowires. The computational study is accompanied by an
      experimental demonstration on Si/SiO2 multilayers. Finite element results are
      found to be well aligned with experimental observations and theoretical
      predictions. Stronger interaction is evident with a curved crack front modeling
      as well as with increasing first and decreasing second Dundurs' parameters.
      Therefore cracks can be packed closer with decreasing film stiffness.

PMID- 20032556
TI  - Si nanocrystal synthesis in HfO2/SiO/HfO2 multilayer structures.
AB  - The synthesis of two-dimensional arrays of Si nanocrystals in an HfO2 matrix has
      been achieved by deposition of HfO2/SiO/HfO2 multilayer structures followed by
      high temperature (1100 degrees C) thermal treatment in nitrogen atmosphere.
      Silicon out-diffusion from the SiO layer through the HfO2 films has been shown to
      be the limiting factor in the formation of the Si nanocrystals. Suitable
      strategies have been identified in order to overcome this limitation. Si
      nanocrystal formation has been achieved by properly adjusting the thickness of
      the SiO layer.

PMID- 20032557
TI  - Precise Ge quantum dot placement for quantum tunneling devices.
AB  - This study demonstrates the precise placement of Ge quantum dots (QDs) in an SiO2
      or Si3N4 matrix in a self-organized manner by thermally oxidizing SiGe in
      nanostructures. The effectiveness of this method is shown by a variety of
      geometries including nanotrenches, nanorods and polygonal nanocavities.
      Modulating the structural geometry and peripheral spacer materials effectively
      places a single Ge QD in the center of an oxidized SiGe nanostructure or
      individual QDs at the corners (edges). This study also reports the fabrication of
      Ge QD single-electron devices that exhibit clear Coulomb staircases and
      differential conductance oscillations at room temperature.

PMID- 20032558
TI  - The fabrication of vanadium-doped ZnO piezoelectric nanofiber by electrospinning.
AB  - Zn(1-x)V(x)O (x = 0.015, 0.02, 0.025, 0.03, V-ZnO) nanofibers were synthesized by
      electrospinning, and a butterfly-shaped piezoelectric response was measured by
      scanning force microscopy. The diameters of V-ZnO nanofibers with hexagonal
      wurtzite phase are in the range of 50-300 nm. The large piezoelectric coefficient
      d(33) of 121 pm V(-1) was obtained and the high piezoelectric property may be
      attributed to the switchable spontaneous polarization induced by V dopants and
      the easier rotation of V-O bonds under an electric field. The result shows that
      the V-ZnO nanofiber is a promising candidate for nanoscale piezoelectric devices.

PMID- 20032559
TI  - Interrater reliability of a clinical scale to assess knee joint effusion.
AB  - STUDY DESIGN: Clinical measurement. OBJECTIVE: To determine the interrater
      reliability of a knee joint effusion grading scale in an outpatient orthopaedic
      physical therapy clinic. BACKGROUND: Knee joint effusion may indicate joint
      inflammation or irritation. Therefore, objective monitoring of effusion is
      important to decision making regarding patient prognosis and program progression.
      The clinicians in the authors' clinic use a modified stroke test to assess for
      knee joint effusion, which is operationally based on a 5-point grading scale.
      METHODS: Seventy-five patients (44 male, 31 female) receiving outpatient physical
      therapy for a unilateral knee problem, for whom effusion assessment was
      indicated, were tested. The subjects ranged from 16 to 65 years of age. Pairs of
      therapists graded the knee joint effusion using the clinical grading scale. A
      contingency table was constructed and analyzed using Cohen kappa values to
      establish interrater reliability. Percent agreement was also calculated. RESULTS:
      The kappa value was 0.75, observed as a proportion of the maximum possible kappa,
      and the percent agreement was 73%. Fifty-four of 75 pairs of tests had perfect
      agreement. Only 5 had disagreement of 2 grades, and there were no disagreements
      of greater than 2 grades. CONCLUSION: These findings provide evidence to support
      the proposed clinical effusion grading scale as a reliable method to assess knee
      joint effusion between therapists in an outpatient orthopaedic physical therapy
      clinic in patients with unilateral knee dysfunction. Only 5 of 75 ratings
      resulted in disagreement that could result in different clinical decisions being
      made by the therapists.

PMID- 20032560
TI  - Genomic and cDNA cloning, expression, purification, and characterization of
      chymotrypsin-trypsin inhibitor from winged bean seeds.
AB  - A 516-bp winged bean chymotrypsin-trypsin inhibitor (WbCTI) gene was amplified
      from genomic DNA and cDNA isolated from winged bean using a pair of degenerate
      primers designed on the basis of the amino acid sequences of WbCTI. The amplified
      PCR products were cloned and sequenced to confirm their authenticity. DNA
      sequence analysis of the genomic and cDNA clones of WbCTI revealed the same
      nucleotide sequence in the coding region and showed WbCTI to be an intron less
      gene. WbCTI was subcloned into pTrc99A and expressed in Escherichia coli to yield
      a recombinant protein (rWbCTI). rWbCTI was purified by a rapid and single step
      immunoaffinity chromatography method, with an overall yield of 1.1 mg/g of wet
      cells. The homogeneity of the purified protein was checked by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, which showed the presence of a single
      protein band. Functionally rWbCTI is indistinguishable from WbCTI, since both
      inhibit bovine trypsin and chymotrypsin in a 1:1 molar ratio. FPLC binding
      studies also confirmed that rWbCTI binds the proteases in a 1:1 molar ratio.

PMID- 20032561
TI  - Unique myocardial fibrosis pattern by late gadolinium enhanced magnetic resonance
      imaging in a patient with isolated noncompaction of the ventricular myocardium.

PMID- 20032562
TI  - Optimal placement of a superior vena cava cannula in minimally invasive robot
      assisted cardiac surgery.
AB  - BACKGROUND: Minimally invasive robot-assisted cardiac surgery is generally
      performed nowadays. To avoid the interference of a superior vena cava (SVC)
      cannula during surgery, it should be inserted before the operation. The position
      of this cannula is very important because it can cause poor venous drainage
      during operation. The proper position of the SVC cannula was investigated in the
      present study. METHODS AND RESULTS: The position of the SVC cannula using the
      transesophageal echocardiography (TEE) and chest X-ray in 45 patients was
      ascertained. The distances from the SVC cannula tip to the carina, sternal end of
      the right clavicle and the lower margin of the T4 vertebral body on chest X-rays
      were measured. The mean depth of the SVC cannula was 142.0+/-11.6 mm. The
      correlation coefficients of cannula depth with sex, weight and height were 0.519,
      0.399 and 0.382, respectively. CONCLUSIONS: The appropriate depth of an SVC
      cannula has weakly positive relationships with sex, weight and height. The
      results of the present study suggest that chest X-rays might be necessary to
      confirm the appropriate location of the cannula and that TEE might be the method
      of choice for correct positioning of the SVC cannula in minimally invasive robot
      assisted cardiac surgery.

PMID- 20032563
TI  - Transcatheter closure of moderate-to-large patent ductus arteriosus in infants
      using Amplatzer duct occluder.
AB  - BACKGROUND: There are difficulties in transcatheter closure of patent ductus
      arteriosus (PDA) in infants. METHODS AND RESULTS: The 46 infants (mean age 6.2+/
      2.7 months; mean body weight 6.3+/-1.6 kg) who underwent PDA closure using the
      Amplatzer duct occluder (ADO). The indication for using an ADO was a ductus
      diameter > or =2.5 or 3 mm. Device diameter selected was 1-3 mm larger than
      ductal diameter. The mean systolic pulmonary artery pressure was 40.9+/-18.2
      mmHg. The mean Qp/Qs ratio was 3.1+/-1.2. The mean ductus diameter was 3.3+/-0.8
      mm. ADO was successfully deployed in 45 patients. Failure occurred in 1 case. The
      mean diameter of device used was 5.4+/-1.1 mm. No severe complications occurred.
      At the 1-month echocardiographic follow-up, a small residual shunt was present in
      4 of 45 patients and had disappeared in all 4 patients at the 3-month follow-up.
      One patient developed a moderate degree of left ventricular outflow tract
      obstruction 2.3 years after the procedure. CONCLUSIONS: Transcatheter closure of
      PDA in infants using the ADO is a safe and effective method.

PMID- 20032564
TI  - Clinical characteristics of defecation syncope compared with micturition syncope.
AB  - BACKGROUND: Defecation syncope (DS) and micturition syncope (MS) are daily
      excretion-related syndromes that are both classified as situational. However,
      their clinical features seem to be very different, so the present comparative
      study aimed to clarify those of DS. METHODS AND RESULTS: The study population
      consisted of 20 consecutive patients with DS and 37 consecutive patients with MS.
      The DS patients were significantly older than the MS patients (63+/-15 vs 52+/-17
      years, P=0.026). Gender was significantly different (P=0.026): women predominated
      in the DS group (60%) whereas men more commonly had MS (70%). The diurnal
      distribution of syncope differed (P=0.0054): 88% of MS episodes occurred between
      6 pm and 6 am, whereas DS occurred almost equally throughout the 24 h. Syncope
      after drinking alcohol was less common with DS (10%) than with MS (60%)
      (P=0.0003), whereas gastrointestinal tract (GIT) symptoms as a premonitory sign
      were more common with DS (55%) than with MS (3%) (P<0.0001). Positive responses
      to head-up tilt testing did not differ between the DS and MS groups. CONCLUSIONS:
      DS tends to occur in elderly women and without any significant daily
      distribution. Alcohol-related syncope was uncommon in patients with DS, and
      preceding GIT symptoms may be important as predictors or triggering factors.

PMID- 20032565
TI  - Lipid profiles in the untreated patients with Hashimoto thyroiditis and the
      effects of thyroxine treatment on subclinical hypothyroidism with Hashimoto
      thyroiditis.
AB  - To evaluate the prevalence of dyslipidemia in the population of Hashimoto
      thyroiditis, we reviewed medical records on the consecutive 1181 cases with adult
      Hashimoto thyroiditis and 830 cases were adopted for the study. First, the serum
      TSH level increased and serum free T4 level decreased, slightly but
      significantly, with increasing age. There were significant positive correlations
      between serum TSH levels and lipid parameters such as total cholesterol (TC),
      triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), non-HDL-C
      and LDL-C/HDL-C ratio (L/H). In contrast, there were significant negative
      correlations between serum free T4 levels and all of these lipid parameters.
      According to the thyroid function, the cases were classified into 4 groups such
      as thyrotoxicosis (TT), euthyroidism (EU), subclinical hypothyroidism (SH) and
      overt hypothyroidism (OH). TC, HDL-C, non-HDL-C and LDL-C of TT were
      significantly lower than those in EU. In contrast, TC, TG, non-HDL-C, LDL-C, L/H
      and age of OH were significantly higher than those in EU. Interestingly, LDL-C
      and L/H of SH were significantly higher compared with EU. Thirty-two of SH
      patients were treated with small doses of levothyroxine and the effects on the
      lipid profile were examined. The TC, non-HDL-C, LDL-C and L/H were significantly
      decreased after treatment. In conclusion, the prevalence of dyslipidemia
      increases along with hypofunction of the thyroid and T4 replacement therapy may
      improve lipid profile in the cases of SH with Hashimoto thyroiditis.

PMID- 20032566
TI  - Body mass index, fasting plasma glucose levels, and C-peptide levels as
      predictors of the future insulin use in Japanese type 2 diabetic patients.
AB  - Insulin therapy represents the most effective and reliable means of achieving
      satisfactory glycemic control. However, few studies have evaluated the predictors
      of future insulin use. The purpose of this study was to investigate the
      predictors of future insulin use in type 2 diabetic patients. In this study, we
      conducted a chart review of 158 Japanese type 2 diabetic patients admitted to our
      hospital for stringent glycemic control. Of the 158 subjects, 92 satisfied the
      inclusion criteria for this study. We assessed the associations between baseline
      BMI, fasting plasma glucose levels (FPG) and serum and urinary C-peptide levels
      (sCPR and uCPR), and insulin usage at 6 months after discharge. We also computed
      the areas under the curve (AUCs) in receiver operator characteristic (ROC) curves
      for each predictor to predict the future insulin use. After adjustment for
      gender, age, and BMI, the multivariable odds ratios (ORs) for future insulin use
      in the highest tertile as compared with lowest tertile were 0.12 for BMI (95%
      confidence interval (CI), 0.03-0.52), 17.0 for FPG (95% CI, 3.27-88.7), 0.12 for
      sCPR (95% CI, 0.02-0.71), and 0.03 for uCPR (95% CI, 0.00-0.24). Prediction
      analyses showed that the AUCs for BMI, FPG, sCPR, and uCPR were 0.73, 0.76, 0.74,
      and 0.78, respectively, which suggests that the predictive abilities of these
      predictors do not differ substantially. In conclusion, this study suggests that
      BMI, FPG, sCPR, and uCPR are strong predictors of the future insulin use in type
      2 diabetic patients.

PMID- 20032567
TI  - A case of ectopic adrenocorticotropic hormone-producing pancreatic neuroendocrine
      tumor with multiple liver metastases.
AB  - Ectopic adrenocorticotropic hormone (ACTH) production by the pancreatic
      neuroendocrine tumor (p-NET) is relatively rare, and patients with this tumor
      show poor prognosis. In this study, we present the case of a 64-year-old woman
      who presented with ectopic ACTH syndrome due to p-NET with multiple liver
      metastases. Computed tomography revealed that she had multiple masses in the
      liver and a solid mass in the head of the pancreas. Endocrinological examinations
      revealed markedly elevated plasma ACTH (735.0 pg/mL) and cortisol (34.7
      microg/dL) levels associated with hypokalemia (2.7 mEq/L), diabetes and typical
      Cushingoid features. Histological examinations by needle biopsy of liver tumors
      in S5 and S8 indicated metastatic ACTH-producing NET, which was also confirmed by
      venous sampling. The metastatic live tumor was somatostatin receptor (SSTR)-2a-
      and SSTR-5-positive as revealed by immunohistochemical staining, and reverse
      transcription polymerase chain reaction revealed divergent expression patterns of
      SSTRs, pro-opiomelanocortin, and gastrin mRNA. To avoid complications of
      hypercortisolemia, metyrapone was first administered to reduce the cortisol
      levels. After near-normalization of cortisol levels, transarterial
      chemoembolization and somatostatin analogue treatment were performed. The
      combination of these treatments effectively decreased ACTH and cortisol levels
      and also ameliorated hyperglycemia. We have achieved controlled hormone secretion
      and prevented tumor growth in this patient for more than 20 months, suggesting
      that highly individualized treatment for NET should be undertaken because of its
      divergent and heterogeneous characteristics.

PMID- 20032568
TI  - Challenge for novel peptide hormones: from discovery to therapeutic application.

PMID- 20032569
TI  - Relation between physiological variation of renal function and carotid intima
      media thickness in non-diabetic individuals.
AB  - AIM: Moderate to severe renal insufficiency and albuminuria have been shown to be
      independent risk factors for atherosclerosis. However, the association between
      renal function and intima media thick-ness (IMT) in non-diabetic individuals is
      less clear. We therefore investigated the relation between renal function,
      established cardiovascular risk factors and carotid intima media thickness in non
      diabetic individuals. METHODS: 853 non-diabetic participants were included in
      this project. Renal function was estimated using the simplified Modification of
      Diet in Renal Disease (MDRD) formulae, a refit MDRD equation for healthy persons
      (MDRD-1) or the Jellife 2 formula, an age independent estimate of glomerular
      filtration rate (GFR). Carotid arterial intima-media thickness was measured at
      the posterior wall of the common carotid artery and the bulbus (IMT(ACC),
      IMTB(Bulbus)). RESULTS: Weak correlations between IMT(ACC) or IMTB(Bulbus) and
      MDRD were found (r=-0.105, p= 0.002; r=-0.127, p<0.001). and similiar results
      were found for MDRD-1. However, adjustment of that relation for age modified the
      picture. While age was an independent predictor, MDRD or MDRD-1 were not further
      informative. Further adjustment for cardiovascular risk factors confirmed that
      relation. Correspondingly, GFR estimated by the age-independent formula Jellife 2
      was not correlated with IMT. CONCLUSIONS: The results of this study indicate that
      variation of renal function within the normal range is not independently
      associated with carotid intima media thickness in non-diabetic individuals. Crude
      correlations between MDRD and IMT appear to reflect the inter-relation among age,
      eGFR and IMT.

PMID- 20032570
TI  - Effects of atorvastatin on arterial stiffness in chronic kidney disease: a
      randomised controlled trial.
AB  - AIM: Central pulse pressure and measures of arterial stiffness (augmentation
      index (AIx) and aortic pulse wave velocity (PWV)) predict morbidity and mortality
      in patients with stage 2-4 chronic kidney disease (CKD). Although statin therapy
      may be of vascular benefit in patients with CKD, the long-term effect of statins
      on central pulse pressure and arterial stiffness has not been assessed in this
      patient population. Hence, the aim of this study was to assess the long-term
      effects of atorvastatin on arterial stiffness and central blood pressure in
      patients with CKD. METHODS: We enrolled 37 patients with serum creatinine levels
      > 1.36 mg/dL into a randomized, double blind trial. Patients were allocated to
      receive 10 mg of atorvastatin per day (19) or placebo (18) for three years.
      Aortic PWV, AIx, estimated central and brachial blood pressures and were
      determined every nine months. RESULTS: At baseline, there were no significant
      differences in aortic PWV, AIx, central or brachial blood pressures between
      atorvastatin-treated and placebo-treated patients. During the trial, aortic PWV
      significantly (p=0.05) increased in placebo-treated, but not (p=0.10) in
      atorvastatin-treated patients (0.51+/-0.95 vs. 0.30+/-0.75 m/sec/yr; p=0.48).
      This represented a 41% (but not statistically significant) slowing of the rate of
      increase in aortic stiffness. There were no significant changes between groups in
      the rate of change of AIx (atorvastatin -0.15+/-5.65 vs. placebo 0.39+/-5.38%/yr,
      p=0.53) or central pulse pressure (atorvastatin -2.32+/-7.46 vs. placebo -0.36+/
      6.64 mmHg/yr p= 0.61). CONCLUSION: In patients with CKD arterial stiffness
      measured by aortic PWV showed a significant increase over time in placebo-treated
      patients but not in atorvastatin-treated patients.

PMID- 20032571
TI  - Effect of high fat diet without cholesterol supplementation on oxidative stress
      and lipid peroxidation in New Zealand white rabbits.
AB  - AIM: Dietary fats may affect coronary artery disease risk by influencing factors
      other than serum cholesterol. The effect of diets containing coconut oil and
      sunflower oil without cholesterol supplementation on oxidative stress and lipid
      peroxidation were studied in male New Zealand White rabbits. METHODS: Animals
      assigned to four groups (control, cholesterol-fed, coconut oil-fed and sunflower
      oil-fed), given an isocaloric diet and studied for 6 months. The lipid profile,
      reduced glutathione, glutathione peroxidase, superoxide dismutase, vitamin C and
      lipid peroxidation were evaluated at the beginning of the study, at the third
      month and at the end of the study period. RESULTS: Serum lipid values did not
      show significant variation between animals fed coconut oil and sunflower oil, but
      total cholesterol, triglycerides and LDL-cholesterol were significantly higher
      and HDL-cholesterol was reduced in cholesterol-fed animals. Lipid peroxidation
      was higher in cholesterol-fed and sunflower oil-fed rabbits compared to controls
      and coconut oil-fed rabbits. Though other parameters such as reduced glutathione,
      glutathione peroxidase, superoxide dismutase and ascorbate did not vary between
      the two oil-fed rabbit groups, cholesterol-fed rabbits showed severe oxidative
      stress. CONCLUSION: We conclude that in the absence of cholesterol
      supplementation, coconut oil intake up to 30% of daily energy supply did not
      cause hypercholesterolemia or oxidative stress in rabbits.

PMID- 20032572
TI  - An update on the role of markers of inflammation in atherosclerosis.
AB  - In recent years, several studies have used the measurement of carotid intima
      media thickness (IMT) as a marker of early atherosclerosis: IMT has been shown to
      correlate significantly with the presence of coronary artery disease (CAD) and to
      predict fatal and not fatal cerebro- and cardio-vascular events. These findings
      highlight the importance of recognizing and managing early stages of
      atherosclerosis for effective cardiovascular prevention. Beyond traditional
      established cardiovascular risk factors, inflammation has been shown to be
      crucial throughout atherosclerosis from endothelial dysfunction to plaque rupture
      and thrombosis. Several studies have shown the existence of a strong relation
      between CAD and fibrinogen or highly sensitive C-reactive protein (hs-CRP) levels
      and their predictive role has been examined through stratification or
      multivariable statistical analyses: levels of these markers of inflammation have
      been independently associated with the incidence of coronary events after
      adjusting for traditional cardiovascular risk factors. Recent studies have
      further addressed the importance of therapeutical modulation of hs-CRP levels in
      high-risk patients for the prevention of vascular events. The strong relationship
      between hs-CRP and IMT may potentially account for the complex role of hs-CRP and
      IMT in the pathogenesis of cardiovascular events. However, beyond the utility of
      measuring markers of inflammation to assess patients with subclinical carotid
      atherosclerosis at higher risk of vascular events, further studies are needed to
      evaluate the therapeutic implications in this category of patients.

PMID- 20032573
TI  - Impact of lifestyle-related diseases on carotid arterial wall elasticity as
      evaluated by an ultrasonic phased-tracking method in Japanese subjects.
AB  - AIM: We investigated the relationship between coronary risk factors and the
      intima-media thickness (IMT) and wall elasticity of carotid arteries. A new real
      time ultrasonic measurement system that allows measurement of the elasticity of
      the carotid arterial intima-media complex was applied to 350 subjects, who were
      also checked for the presence/absence of hypertension, dyslipidemia, diabetes
      mellitus and regular smoking. Simultaneous measurement of the elastic modulus and
      IMT was conducted at four sites in the bilateral carotid arteries. METHODS AND
      RESULTS: In the group with maximum IMT (max IMT) <1.1 mm, the IMT, as well as the
      mean elastic modulus in the circumferential direction (Etheta), showed positive
      correlations with age and coronary risk factors. Multiple regression analysis
      showed that age, systolic blood pressure and pulse rate remained independent
      determinants of Etheta. The number of criteria fulfilling the diagnosis of
      metabolic syndrome showed a good positive correlation with the value of Etheta in
      the group with max IMT values <1.1 mm. CONCLUSION: Measurement of carotid
      arterial wall elasticity together with IMT is useful to detect dis-tortions in
      intramural elasticity distribution occurring in the early stages of
      atherosclerosis.

PMID- 20032574
TI  - Activating effect of momordin, extract of bitter melon (Momordica Charantia L.),
      on the promoter of human PPARdelta.
AB  - AIM: Bitter melon (Momordica charantia L.) is a common vegetable grown in Okinawa
      that has also been used recently in medicine for the treatment of diseases such
      as diabetes, hypertension, and dyslipidemia. Among Bitter melon extracts
      compounds, we focused on an extract known as momordin in the present study, to
      examine its effect on peroxisome-proliferator activated-receptor (PPAR) delta
      (also called PPARdelta in rodents) expression and promoter activity of the human
      PPARdelta gene. METHODS: A human PPARdelta promoter-reporter plasmid was made as
      a template from a BAC CLONE (RPCI-11C) containing a -3076 bp (BglI site) +74 bp
      (EcoRI site) sequence. Luciferase assay of PPARdelta promoter activity was
      performed using HepG2 cells. RESULTS: 10 and 25 nM Momordin significantly
      increased the expression of PPARdelta mRNA 1.5-fold (relative to the control).
      Moreover, 10 and 25 nM Momordin significantly increased PPARdelta promoter
      activity in a dose-dependent manner, reaching more than 1.5-fold relative to the
      control. CONCLUSION: Our present data obtained through successful cloning of the
      PPARdelta promoter demonstrate that PPARdelta production and activation are
      upregulated through PPARdelta promoter activity following momordin treatment.

PMID- 20032575
TI  - Assessment of an ELISA kit for platelet-derived microparticles by joint research
      at many institutes in Japan.
AB  - AIM: Platelet-derived microparticles (PDMPs) play roles in normal hemostatic
      responses to vascular injury because they possess prothrombinase activity.
      Although the most widely used method for studying PDMP is flow cytometry, we
      previously developed an enzyme-linked immunosorbent assay (ELISA) method as an
      easier and more reproducible PDMP assay. The purpose of this study was to use
      various clinical settings to verify whether this ELISA method can produce
      equivalent results to flow cytometry for PDMP. METHODS: We performed a large
      scale clinical study for various thrombotic and subatherothrombotic diseases
      using an ELISA kit. The study group included 692 patients with cerebral
      infarction, heart failure, acute coronary syndrome or diabetes mellitus. RESULTS:
      When baseline PDMP values in the various diseases were compared with those in
      healthy controls, significant differences were noted in all cases. There were
      significantly elevated levels of PDMPs in diabetic patients with complications
      but no thrombosis. When baseline PDMP values in cerebral infarction were compared
      within the subclassifications, atheroma and other types of infarction exhibited
      significantly elevated PDMP levels compared with lacunar infarction. Cerebral
      infarction exhibited a significant change in PDMPs after therapy compared with
      the baseline (before therapy), but not in acute coronary syndrome and heart
      failure. The ELISA method exhibited results almost identical to flow cytometry
      for PDMP in various atherothrombotic diseases. CONCLUSION: Although further
      examinations to evaluate the therapeutic usefulness of these diseases are
      necessary, ELISA kits possibly represent a new tool for PDMP related to
      atherothrombosis.

PMID- 20032576
TI  - Impact of changes in waist circumference and BMI over one-year period on serum
      lipid data in Japanese individuals.
AB  - AIM: Loss or gain in obesity indexes, such as body mass index (BMI) and waist
      circumference (WC), may affect serum lipid parameters. We therefore analyzed the
      impact of changes in WC and BMI over a one-year period on serum levels of LDL
      cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). METHODS: We
      analyzed the data of 3,111 individuals who were not on lipid- lowering medication
      and who underwent general health screening two years running. RESULTS: The
      correlation between percent changes of WC (%dWC) and BMI (%dBMI) were both
      statistically significantly correlated with percent changes in LDL-C (%dLDL), HDL
      C (%dHDL), and TG (%dTG) except that between %dWC and %dHDL in women. In multiple
      regression analysis, %dBMI, but not %dWC, was found to be an independent
      predictor of %dLDL, %dHDL, and %dTG. When %dBMI was excluded from the variables,
      %dWC was identified as an independent factor predicting %dLDL and %dTG; however,
      in individuals with %dBMI of > or =0, %dWC was not found to be a predictor of
      percent changes in any lipid parameters tested in this model. CONCLUSION: Percent
      changes in BMI were found to be an independent predictor of adverse changes in
      lipid parameters in both genders. Although percent changes in WC (%dWC) also
      tended to confer adverse changes in lipid parameters, this relationship did not
      remain statistically significant after controlling for %dBMI. It is suggested
      that changes in obesity parameters are an important goal to avoid adverse lipid
      changes, although there might be some gender differences.

PMID- 20032577
TI  - RhoA and Rac1 changes in the atherosclerotic lesions of WHHLMI rabbits.
AB  - AIM: The activation of RhoA and Rac1 is crucial for the pathogenesis of
      atherosclerosis. This study investigated the changes of unprocessed and mature
      forms of RhoA and Rac1 in the progression of atherosclerosis. METHODS:
      Unprocessed and geranylgeranylated forms of RhoA and Rac1 in aortic
      atherosclerotic lesions were separated by the Triton X-114 partition method using
      Watanabe heritable hyperlipidemic (WHHLMI) rabbits prone to myocardial
      infarction. The activation of RhoA and Rac1 was determined by membrane
      translocation and pull-down assays. RESULTS: The levels of unprocessed RhoA and
      Rac1 of the aortas were higher at 7 months than 3 months, accompanied by
      increased levels of total RhoA and Rac1. Membrane-bound RhoA and Rac1 levels of
      the aortas at 7 months were significantly increased compared with those at 3
      months, consistent with the results of GTP-loading. Unprocessed and activated
      forms of RhoA and Rac1 had gradually decreas at 15 and 24 months compared to 7
      months. CONCLUSIONS: We show evidence of marked increases in unprocessed RhoA and
      Rac1 with enhanced activities in the progression of atherosclerosis in WHHLMI
      rabbits. This is important for better understanding of the pathogenesis of
      hyperlipidemia-dependent atherosclerosis.

PMID- 20032579
TI  - Effects of obstructive sleep apnea with intermittent hypoxia on platelet
      aggregability.
AB  - AIM: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular diseases.
      Platelets play key roles in the development of atherothrombosis. Several studies
      assessing platelet activation in patients with OSA have been published; however,
      there have been only a few studies with a small number of patients with OSA
      investigating platelet aggregability, which evaluates platelet aggregation more
      directly than the platelet activation status. We aimed to investigate the effects
      of OSA and nasal continuous positive airway pressure (nCPAP) therapy, a well
      established treatment for OSA, on platelet aggregability. METHODS AND RESULTS: We
      examined 124 consecutive patients with snoring in whom the 3% oxygen desaturation
      index (3%ODI), a severity marker of OSA, and ADP- and collagen-induced platelet
      aggregability measured with the optical aggregometer were analyzed. ADP-induced
      platelet aggre-gability was increased more in patients with moderate-to-severe
      OSA (3%ODI>15) than in patients with non-to-mild OSA (p=0.029). In multiple
      linear models, 3%ODI significantly contributed to increased platelet
      aggregability induced by both ADP and collagen among 59 subjects with one or more
      risk factors for vascular diseases, such as smoking, hypertension, diabetes
      mellitus or hyperlipidemia. In 23 patients treated by nCPAP, collagen-induced
      platelet aggregability was ameliorated on Day 90, compared to at the baseline.
      CONCLUSION: The severity of OSA significantly contributed to platelet
      aggregability, which was improved by nCPAP treatment partially at three months.

PMID- 20032580
TI  - Expression of perilipin and adipophilin in nonalcoholic fatty liver disease;
      relevance to oxidative injury and hepatocyte ballooning.
AB  - AIMS: Perilipin and adipophilin, PAT family proteins, play important roles in
      lipid metabolism. Although nonalcoholic fatty liver disease (NAFLD) is initiated
      by hepatocyte lipidation, little is known about the relationship between these
      proteins and hepatocellular injury. We investigated the expressions of perilipin
      and adipophilin and their relation to inflammation, fibrosis, hepatocellular
      ballooning, and oxidized phosphatidylcholine (oxPC) localization in human NAFLD.
      METHODS AND RESULTS: Liver biopsies of nonalcoholic steatohepatitis (NASH, n=39)
      or simple steatosis (n=9) were studied by immunohistochemical techniques using
      anti-perilipin, anti-adipophilin and anti-oxPC antibodies. The severity of liver
      damage was histologically assessed by the Brunt system and NAFLD activity score
      (NAS). Enlarged hepatocytes usually containing Mallory-Denk bodies were defined
      as ballooned. Perilipin and adipophilin were detected on the rim of lipid
      droplets in both NASH and simple steatosis. Perilipin was more evident in larger
      lipid droplets while adipophilin expression was frequent in lipid droplets of
      ballooned hepatocytes. The frequency of adipophilin-positive ballooned
      hepatocytes was correlated to inflammation (Rs=0.72, p<0.0001), fibrosis
      (Rs=0.46, p=0.005), NAS (Rs=0.47, p=0.004) and oxPC-positive ballooned
      hepatocytes (Rs=0.35, p=0.033). CONCLUSIONS: Expression patterns of perilipin and
      adipophilin in NASH livers varied with the size of lipid droplets. In partiew or,
      adipophilin expression in ballooned hepatocytes was closely associated with
      oxidative damage.

PMID- 20032581
TI  - Statin-induced Ca(2+) release was increased in B lymphocytes in patients who
      showed elevated serum creatine kinase during statin treatment.
AB  - AIM: Statins are effective in lowering cholesterol levels, but cause fatal
      rhabdomyolysis in susceptible individuals. Because it has been hypothesized that
      muscle damage could result from alterations in Ca(2+) homeostasis in muscle
      cells, we tested whether measuring statin-induced changes in intracellular
      calcium ([Ca(2+)](i)) is useful for predicting susceptibility to statin-muscle
      damage, using human CD19+ primary B lymphocytes. METHODS: Statin-induced
      alterations in [Ca(2+)](i) were studied using the human THP-1 cell line and CD19+
      primary B lymphocytes. Changes in [Ca(2+)](i) were measured directly in fluo-3-
      loaded cells using either single or dual-color flow cytometry. RESULTS: The
      Ca(2+) release study suggested that statin-induced changes in [Ca(2+)](i) were
      due to Ca(2+) release from ryanodine-sensitive Ca(2+) stores and mitochondrial
      compartments. Further, statin users who experienced elevated creatine kinase
      (n=8) exhibited significantly greater statin-induced Ca(2+) release in B cells
      than healthy volunteers (n=45) and statin users without elevated creatine kinase
      (n=16), while no difference was seen between the latter two groups. CONCLUSION:
      Statin-induced Ca(2+) release from ryanodine-sensitive stores and mitochondria
      may contribute to myotoxicity. The laboratory test for Ca(2+) release using CD19+
      primary B lymphocytes may be useful to predict susceptibility to statin-induced
      muscle toxicity prior to statin use.

PMID- 20032578
TI  - Current trends in lifestyle-related disease management by general practitioners:
      a report from the "Heart Care Network" groups.
AB  - AIMS: In Japan, it is believed that guidelines for lifestyle-related disease are
      used in routine clinical practice, however, there are few reports on the actual
      rate of healthcare conducted in accordance with these guidelines by general
      practitioners and on their usefulness in preventing cardiovascular events.
      Therefore, the Heart Care Network (HCN) groups were organized mainly by general
      practitioners treating lifestyle diseases in 62 areas of Japan. METHODS: The HCN
      has collected data on lifestyle diseases in high-risk patients in routine
      practices and investigated management conditions, guideline target achievement
      rates and medication. Additionally, the incidence of cardiovascular events was
      assessed. RESULTS: We analyzed 14,064 cases. The lipid profile, blood pressure,
      glycemic control were significantly improved over the 3 years. The incidence of
      cardiovascular events were significantly reduced by the achievement of target LDL
      cholesterol, systolic blood pressure and hemoglobin A1c and even after adjustment
      for age, gender, history of myocardial infarction, the reduction of these
      lifestyle-related parameters remains significant. CONCLUSION: These results
      revealed the current trends in the healthcare activities of general
      practitioners, the management conditions for lifestyle diseases in CHD high-risk
      patients and their effects on reducing cardiovascular events.

PMID- 20032582
TI  - Imaging of structural changes in endothelial cells and thrombus formation at the
      site of FeCl(3)-induced injuries in mice cremasteric arteries.
AB  - AIM: We investigated thrombus formation at the site of functional injury to
      endothelial cells by FeCl(3). METHODS: After preparation of cremasteric arteries
      of mice, controlled endothelial injury was induced by application of FeCl(3).
      Endothelial cells were rendered fluorescent by addition of FITC (fluorescein
      isothiocyanate)-labeled isolectin B4. Circulating platelets and leukocytes were
      made fluorescent by rhodamine 6G. Three-dimensional (3D) growth of thrombi was
      visualized in real time. Effects of aspirin and clopidogrel pre-treatments on the
      growth of thrombi were investigated in vivo as well as in an ex vivo flow chamber
      system. RESULTS: Endothelial cells were tightly bound to each other to protect
      local thrombus formation. Platelets started to adhere to endothelial cells when
      FeCl(3) was applied. Three-dimensional growth of thrombi, which takes 10.6+/-7.5
      minutes for complete occlusion in control, can be visualized with our imaging
      system. Aspirin pre-treatment at the dose tested did not influence either
      endothelial injury or platelet thrombus growth, while clopidogrel pretreatment
      significantly inhibited 3D growth and prolonged occlusion time up to 64.6+/-25.3
      minutes (100 mg/kg). A similar inhibiting effect of clopidogrel was reproduced in
      ex vivo flow chamber experiments. CONCLUSIONS: We have developed an in vivo
      system to detect thrombus formation after functional damage to the endothelium.

PMID- 20032583
TI  - Distribution of smooth muscle cells and macrophages expressing scavenger receptor
      BI/II in atherosclerosis.
AB  - AIM: Scavenger receptors type I and II (SRBI/II) have dual roles in both
      atherogenic and antiatherogenic functions through interactions with lipoproteins
      and their expression in macrophages; how-ever, the distribution and density of
      SRBI/II-positive macrophages and smooth muscle cells (SMCs) as well as their
      association with lipid metabolism-related proteins in atherosclerotic intima of
      the human aorta remain unclear. METHODS: Autopsied aortic tissues were double
      immunostained with SRBI/BII and smooth muscle actin or macrophage-specific
      antibodies. The density of SRBI/BII-positive SMCs and macrophages in intimal
      lesion was measured. They were also immunostained with antibodies against four
      apolipoproteins, four phospholipase A2s, and CETP. RESULTS: SRBI/II was expressed
      in both macrophages and SMCs distributed in various intimal lesions. The density
      of SRBI/II-positive SMCs in intimal lesions significantly decreased with the
      advance of atherosclerosis, whereas the density of SRBI/II-positive macrophages
      significantly increased with atherosclerotic development. In addition, functional
      proteins, such as apolipoproteins, secretory phospholipase A2s, and CETP, were
      distributed in the intimal stroma around SRBI/II-positive cells in all lesion
      types. CONCLUSION: The results indicated that SMCs are involved in lipid
      metabolism via SRBI/II expression mainly in the early stages of atherosclerosis
      evolution, and that SRBI/II-positive macrophages are mainly involved in advanced
      stages.

PMID- 20032584
TI  - Usefulness of GPT for diagnosis of metabolic syndrome in obese Japanese children.
AB  - AIM: The aim of this study was to evaluate the usefulness of glutamate pyruvate
      transaminase (GPT) levels in the diagnosis of metabolic syndrome (MS) in obese
      Japanese children. METHODS: We examined 193 obese boys (mean age: 12.1 yrs; mean
      percent overweight [POW]: 53.9%) and 37 obese girls (mean age: 11.4 yrs; mean
      POW: 57.2%). Anthropometric measurements, blood pressure and levels of liver
      transaminases, serum lipids and lipoproteins, fasting blood glucose (FBG), serum
      insulin and adiponectin were measured. The subjects were divided into either an
      MS or a non-MS group according to the MS definition criteria for Japanese
      children. RESULTS: The level of GPT was significantly higher in the MS group in
      both genders. Correlation analysis revealed positive correlations between GPT and
      waist circumference, blood pressure, maximum preperitoneal fat thickness, serum
      insulin and homeostasis model assessment-insulin resistance (HOMA-R), but no
      correlation between GPT and FBG. ANOVA showed a significant difference in GPT
      levels between MS and non-MS subgroups, whereas there was no difference in FBG
      between the two groups. Receiver operating characteristic curves demonstrated
      that GPT was clearly superior to FBG as a diagnostic marker of MS. CONCLUSION: We
      conclude that an elevation in GPT in obese children most likely reflects insulin
      resistance and that GPT is superior to FBG as a marker of MS.

PMID- 20032585
TI  - Deficiency of clusterin inhibits neointimal hyperplasia after vascular injury.
AB  - AIM: Increased clusterin mRNA and protein levels have been detected in various
      tissues undergoing stress, and we previously reported that clusterin is markedly
      induced in media and neointima following vascular injury. The present study
      therefore investigated the impact of clusterin on neointimal hyperplasia
      following vascular injury. METHODS AND RESULTS: As compared with wild-type mice,
      clusterin knockout mice (clusterin-KO) demonstrated a significant decrease of the
      intima/media ratio 4 weeks after cuff placement. Immunohistochemical analysis of
      injured femoral arteries in clusterin-KO demonstrated the accumulation of p53 in
      nuclei of neointimal vascular smooth muscle cells (VSMCs). Moreover, VSMCs from
      either clusterin-KO or rat VSMCs treated with clusterin-short-interfering (si)
      RNA subjected to static stretch exhibited significantly increased p53 and p21,
      and increased G1 cell cycle arrest as indicated by flow cytometry compared with
      VSMCs from wild-type mice. CONCLUSION: Reduced clusterin expression reduced the
      proliferation of VSMCs and induced G1 arrest via p53 and p21. Clusterin therefore
      represents a promising molecular target to limit restenosis after coronary
      intervention.

PMID- 20032586
TI  - Fasting plasma glucose and incidence of diabetes --- implication for the
      threshold for impaired fasting glucose: results from the population-based Omiya
      MA cohort study.
AB  - AIM: In 2003, the American Diabetes Association recommended that the threshold
      for diagnosing impaired fasting glucose (IFG) should be lowered from 6.1 mmol/L
      (110 mg/dL) to 5.6 mmol/L (100 mg/dL). To discuss the diagnostic threshold for
      IFG, the association between fasting plasma glucose (FPG) and the risk of future
      diabetes must be known; however, data regarding this relation in the Japanese
      population are scarce. The aim of this study was to determine the relation
      between FPG and the risk of future diabetes in the Japanese general population.
      METHODS: A retrospective cohort study was conducted using data from annual health
      check-ups performed in Omiya city. A total of 11,369 subjects between the ages of
      40-79 years who were not diabetic at baseline were followed for seven years.
      Diabetes was defined as FPG > or =126 mg/dL or self-report. RESULTS: The
      incidence of diabetes increased as the baseline FPG level increased and a similar
      pattern was observed irrespective of sex or age. The hazard ratios compared with
      subjects with FPG <85 mg/ dL adjusted for possible confounding factors were 3.83
      (95% confidence interval (95% CI); 2.41-6.08) for subjects with 100 to 104 mg/dL
      FPG and 7.87 [corrected] (95% CI; 4.98-12.4) for subjects with 105 to 109 mg/dL
      FPG. CONCLUSIONS: Subjects with 100-109 mg/dL FPG have an appreciable risk of
      diabetes that cannot be considered as "normal" and should be notified of their
      potential risk of developing diabetes.

PMID- 20032587
TI  - Lower high-density lipoprotein cholesterol is a significant and independent risk
      for coronary artery disease in Japanese men.
AB  - AIM: Lower levels of high-density lipoprotein cholesterol (HDL-C) have been
      recognized as a risk factor for coronary artery disease (CAD), but the
      relationship between HDL-C values and the occurrence of CAD has not been fully
      established in the Japanese general population. METHODS: A cohort study of 5,371
      Japanese men with 12 years of follow-up was conducted to identify risk factors
      for the occurrence of CAD. RESULTS: One hundred and twelve subjects had CAD
      (acute myocardial infarction in 67 patients and angina in 45 patients) during the
      follow-up period. Adjustment for variables including age, body mass index,
      smoking habit, alcohol intake, systolic blood pressure, low-density lipoprotein
      cholesterol, triglyceride, fasting plasma glucose, hypertension, diabetes
      mellitus and hyperlipidemia, adjusted hazard ratio (HR) of lower levels of HDL-C
      for the occurrence of CAD was 1.21 (95% confidence interval (CI): 1.11-1.33,
      p<0.001). Serum HDL-C concentration less than 51 mg/dL was a significant risk for
      CAD. CONCLUSIONS: Low HDL-C was identified as a significant and independent risk
      for CAD in Japanese men using long-term follow-up data.

PMID- 20032588
TI  - Association between arterial stiffness and estimated glomerular filtration rate
      in the Japanese general population.
AB  - AIM: Chronic kidney disease (CKD) is associated with an increased risk of
      cardiovascular disease, although it has yet to be established whether CKD is an
      independent risk factor for arterial stiffness in community residents. The
      purpose of this study was to determine the correlation between the cardio-ankle
      vascular index (CAVI) and estimated glomerular filtration rate (eGFR) in the
      general population. METHODS: We studied 881 consecutively enrolled subjects
      undergoing health checkups. CAVI was calculated automatically from the pulse
      volume record, blood pressure and the vascular length from the heart to the
      ankle. CKD was evaluated by the eGFR. RESULTS: The distribution of eGFR was as
      follows: 241 with eGFR (mL/min/1.73m(2)) > or =90; 572 with eGFR 60-89; 65 with
      eGFR 30-59; 3 with eGFR 15-29; 0 with eGFR <15. Linear regression analysis showed
      that CAVI was negatively correlated significantly with eGFR, while multiple
      regression analysis using CAVI as an objective variable, adjusted for
      conventional atherosclerotic risk factors and eGFR as explanatory variables,
      demonstrated that CAVI was an independent determinant of eGFR. We also showed
      that stepwise increments of CAVI occurred with progressive deterioration of CKD.
      CONCLUSION: CAVI was independently correlated with eGFR indicating that CKD is
      associated with arterial stiffness in the general population.

PMID- 20032589
TI  - Basic occupational health services in Baoan, China.
AB  - OBJECTIVES: The aim of the study was to develop a model of basic occupational
      health services (BOHS) in Baoan, which could provide occupational health services
      (OHS) universally for workers and control occupational hazards. METHODS: Steps
      involved in the BOHS strategy included construction of the BOHS system, capacity
      building, health training and education, surveillance of workplaces and the
      health of workers, risk assessment, control and evaluation processes. RESULTS:
      This model provided BOHS to employees universally, especially migrant workers in
      small- and medium-sized enterprises (SMEs) who had been underserved. It expanded
      the coverage of OHS and improved their content. The knowledge and recognition
      rate of occupational diseases, the coverage rates of working places and workers
      rose significantly after three years development. Furthermore, BOHS were cost
      effective and accepted by both employers and employees. CONCLUSIONS: Our
      experience suggests that a BOHS strategy might be a feasible and effective way of
      protecting the health of workers confronted with occupational hazards.

PMID- 20032590
TI  - Interactive model of subsidiary behaviors, work performance and autonomic nerve
      activity during visual display terminal work.
AB  - OBJECTIVES: The aims of the study were to investigate the systematic
      classification of subsidiary behaviors during visual display terminal (VDT) work
      and discuss the interpretation of these behaviors through an interactive model of
      subsidiary behaviors, work performance and autonomic nerve activity. METHODS:
      Twelve university students were instructed to perform continuous 120-min English
      transcription tasks in a sedentary posture. Data on subsidiary behaviors, work
      performance (mean keystroke and mean error rates), and autonomic nervous system
      balance (log-transformed low frequency (LF) / high frequency (HF) ratio) were
      recorded every 5 min during VDT work. RESULTS: The subsidiary behaviors were
      categorized into 3 qualitatively independent factors: distractive behaviors
      against monotony (DBM), sleepiness-related behaviors (SRB), and habitual
      behaviors (HB). A cross-correlation analysis indicated that an increase of DBM,
      which is considered as a sign of workers' attempt to escape from monotonous task
      operations, was related to a decline in performance. A decrease in the LF/HF
      ratio was followed by SRB after 5 min passed (r=-0.57, p<0.05), eventually
      leading to a restriction of the deterioration in performance. An increase of DBM
      was predictive of an increase in errors (r=0.54, p<0.05), and a significant
      negative correlation (r=-0.46, p<0.05) between HB and autonomic nerve activity at
      10 min after the appearance of HB was observed. CONCLUSION: It emerged from the
      results that the factor structure of subsidiary behaviors consists of 3 mutually
      independent factors. The interactive model suggests that subsidiary behaviors are
      possibly precursory signs of errors and changes in autonomic nervous system
      balance.

PMID- 20032591
TI  - Relationship of job satisfaction, psychological distress and stress-related
      biological parameters among healthy nurses: a longitudinal study.
AB  - OBJECTIVE: To examine the relationship between job satisfaction, psychological
      distress, psychosocial processes and stress-related biological factors, and to
      evaluate whether over time changes of work satisfaction could affect the
      immunological-inflammatory status of workers. METHODS: One hundred and one nurses
      were enrolled at the Clinic of Occupational Medicine, Polytechnic University of
      Marche, Ancona, Italy. Perceived job satisfaction, psychological distress, and
      social support were assessed every 4 mo over a 1-yr period using 4 self-reported
      questionnaires. T lymphocytes CD3, CD4(+), CD8(+), CD8(+)-CD57(+), B lymphocyte
      CD19(+), NK cells CD56(+), and NK cell activity were determined. RESULTS: Job
      satisfaction was associated with reduced psychological distress and was
      characterized by low cell numbers of CD8(+) suppressor T cells, CD8(+)-CD57(+)
      activated T cells, CD56(+) NK cells and low IL-6 levels. Over time changes in
      psychological parameters were related to changes in the immunological
      inflammatory variables. Subjects who increased their job satisfaction showed a
      reduced psychological stress associated with reduced number of CD8(+)-CD57(+)
      activated T cells and inflammatory cytokines. CONCLUSIONS: Job (dis)satisfaction
      is related with psychological mechanisms in stress affecting cellular immune
      function.

PMID- 20032592
TI  - "Our research". Preface.

PMID- 20032593
TI  - Some nutritional characteristics of kernel and oil of peanut (Arachis hypogaea
      L.).
AB  - Some nutritional properties of the peanut kernel and oils were established. The
      oil yields from these kernels vary from 32.7 % to 45.4 %. The content of protein
      ranged between 25.9 % to 32.4 %, with a mean value of 28.93 %. The mineral
      contents of peanut kernels were determined by Inductively Coupled Plasma Atomic
      Emission Spectrometry (ICP-AES). The contents of Na ranged from 867.7 mg/kg to
      1186.1 mg/kg, with a mean value of 1004.7 mg/ kg. The phosphor contents of
      kernels ranged between 2769.7 mg/kg to 3784.9 mg/kg, with a mean value of 3433.91
      mg/kg. The oil had a refractive Index (n 20) between 1.451 to 1.461 and a
      saponifiable value between 165.3 to 187.6. The main fatty acids in peanut kernel
      oils are oleic, linoleic and palmitic. Statistical differences between parameter
      to locatins were important at p < 0.05. As a result, the present study showed the
      peanut kernels of the researched species of Arachis kernels from Turkey to be a
      potential source of valuable oil which might be used for edible and other
      industrial applications.

PMID- 20032594
TI  - Composition and thermal characteristics of Madhuca longifolia seed fat and its
      solid and liquid fractions.
AB  - This study was to characterize the seed fat from Madhuca longifolia known as Mee
      fat and its solid and liquid fractions with the objective of distinguishing them.
      A sample of Mee fat was partitioned into solid and liquid fractions using acetone
      as the solvent medium. The isolated fractions were compared to the native Mee fat
      sample with respect to various physico-chemical parameters using standard
      chemical methods as well as instrumental techniques such as, gas liquid
      chromatography (GLC), reversed-phase high performance liquid chromatography (RP
      HPLC), and differential scanning calorimetry (DSC). Basic analyses indicated that
      there were wide variations between the native sample and its fractions with
      respect to iodine value (IV), and slip melting point (SMP). The cloud point (CP)
      of the liquid fraction was found to be 10.5 degrees C. Fatty acid compositional
      analyses showed that the proportion of saturated fatty acids (SFA) such as
      palmitic and stearic went up in the high-melting fraction (HMF) while in low
      melting fraction (LMF) the proportion of unsaturated fatty acid (USFA) such as
      oleic and lenoleic increased. According to the HPLC analyses, Mee fat had a
      tiacyl glycerol (TAG) sequence similar to that of palm oil. After fractionation,
      the solid and liquid fractions obtained were found to have TAG profiles very much
      different from the native sample. Thermal analyses by DSC showed that Mee fat had
      two-widely separated high and low melting thermal transitions, a feature which
      was beneficial for the effective separation of solid and liquid fractions. The
      thermal profiles displayed by the fractions were clearly distinguishable from
      that of the native sample.

PMID- 20032595
TI  - Synthesis and characterization of fatty hydroxamic acids from triacylglycerides.
AB  - In this study, fatty haydroxamic acids (FHAs), which have biological activities
      as antibiotics and antifungal, have been synthesized via refluxing of
      triacylglycrides, palm olein, palm stearin or corn oil with hydroxylamine
      hydrochloride. The products were characterized using the complex formation test
      of hydroxamic acid group with zinc(I), copper(II) and iron(III), various
      technique methods including nuclear magnetic resonance ((1)H NMR) spectroscopy,
      Fourier transform infrared (FTIR) spectroscopy and elemental analysis. Parameters
      that may affect the conversion of oils to FHAs including the effect of reaction
      time, effect of organic solvent and effect of hydro/oil molar issue were also
      investigated in this study. Results of characterization indicate that FHAs were
      successfully produced from triacylglycrides. The conversion percentages of palm
      stearin, palm olein and corn oil into their fatty hydroxamic acids are 82, 81 and
      78, respectively. Results also showed that hexane is the best organic solvent to
      produce the FHAs from the three oils used in this study. The optimum reaction
      time to achieve the maximum conversion percentage of the oils to FHAs was found
      to be 10 hours for all the three oils, while the optimum molar ration of hydro/to
      oil was found to be 7:1 for all the different three oils.

PMID- 20032596
TI  - CH/pi interaction between benzene and hydrocarbons having six carbon atoms in
      their binary liquid mixtures.
AB  - Molecular interactions between benzene and hydrocarbons having six carbon atoms,
      such as hexane, cyclohexane and 1-hexene in their binary liquid mixtures were
      studied through the measurements of density, viscosity, self-diffusion
      coefficient, (13)C NMR spin-lattice relaxation time and (1)H NMR chemical shift.
      CH/pi attraction between hexane and benzene in their binary mixture was observed
      in a relatively benzene rich region, whereas a special attractive interaction was
      not observed between cyclohexane and benzene. On the other hand, 1-hexene and
      benzene in their binary mixtures were characteristic in their self-diffusion
      coefficient behaviors: 1-hexene more strongly attract benzene not only by the
      CH/pi attraction but also probably by the p/p interaction between the double bond
      in 1-hexene and the p-electron in benzene ring.

PMID- 20032597
TI  - Decreases in surface activities and aquatic toxicities of linear alkylbenzene
      sulfonate and alcohol ethoxylates during biodegradation.
AB  - We discussed the relation between aquatic toxicity and interfacial activity
      during biodegradation with using LAS (Linear Alkylbenzene Sulphonate) and AE
      (Alcohol Ethoxylate). The change of death rate of Daphnia magna, surface tension,
      concentration of surfactant, and biodegradation by oxygen demand during
      biodegradation were measured. As a result, a rapid decrease in toxicity and rapid
      increase in surface tension were observed within the time before biodegradation
      based on oxygen demand started to increase. These rapid changes in toxicity and
      surface tension occurred due to the structural change of surfactant molecules in
      the primary biodegradation process, which was confirmed by HPLC (High Performance
      Liquid Chromatography) analysis. We also performed re-addition test to study the
      effects of acclimatization since it takes an important role on boidegradation,
      and found that the acclimatization significantly accelerated the primary
      biodegradation, which were indicated by increase in surface tension and decrease
      in aquatic toxicity. These results show that the environmental risk of
      surfactants should be considered not only with the biodegradation based on oxygen
      demand but also with the decrease of interfacial activity through the primary
      biodegradation process.

PMID- 20032598
TI  - A novel body weight-loss promoting oil prepared with vegetable protein.
AB  - It has been reported that oil thermally processed with wheat gluten (gluten oil)
      exhibited safe weight-loss promoting effects in animal experiments. However, as
      the oil has a high color index, and its chemical properties and smell differ from
      those of fresh oil, it is uncertain if the oil will find market acceptance. In
      order to resolve the issue, frying oil was heated with soybean protein under
      reduced pressure (soybean protein oil), resulting in a product with an
      appearance, chemical properties and smell comparable to those of fresh oil. This
      improved oil was mixed (7 wt%) with powdered AIN93G no fat, defined standard diet
      and fed to 10-week-old Wistar rats ad libitum. The experimental rats grew
      normally, ingesting the same amount as that of the control rats; however, there
      was a negative correlation between body weight increases and fecal weight
      increases. After the 12-week feeding period, all the rats were sacrificed to
      obtain blood and organs. In the experimental group, liver weight, retroperitoneal
      fat tissue weight and serum triacylglycerol (TG) levels decreased significantly.
      Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
      histological analysis supported the safety of the improved oil. In conclusion, it
      was found that soybean protein oil inhibited body weight increases without any
      adverse effects in animal experiments. The oil holds promise as a novel dieting
      oil that steadily decreases body weight at an appropriate rate.

PMID- 20032599
TI  - Melanogenesis inhibitory activities of iridoid-, hemiterpene-, and fatty acid
      glycosides from the fruits of Morinda citrifolia (Noni).
AB  - A new iridoid glycoside, 9-epi-6alpha-methoxy geniposidic acid (4), three new
      hemiterpene glycosides, 3-methylbut-3-enyl 2'-O-(beta-D-glucopyranosyl)-beta-D
      glucopyranoside (nonioside K) (6), 3-methylbut-3-enyl 6'-O-(beta-D-xylopyranosyl)
      beta-D-glucopyranoside (nonioside L) (8), and 3-methylbut-3-enyl 6'-O-(beta-D
      xylofuranosyl)-beta-D-glucopyranoside (nonioside M) (9), and two new saccharide
      fatty acid esters, 6'-O-(beta-D-glucopyranosyl)-1'-O-[(2xi)-2-methylbutanoyl]
      beta-D-glucopyranose (nonioside N) (16) and 6'-O-(beta-D-xylopyranosyl)-1'-O
      [(2xi)-2-methylbutanoyl]-beta-D-glucopyranose (nonioside O) (17), were isolated
      from a methanol extract of the fruits of Morinda citrifolia (noni), along with 11
      known compounds, namely, three iridoid glycosides (1-3), two hemiterpene
      glycosides (5 and 7), and five saccharide fatty acid esters (10-15). Upon
      evaluation of compounds 1-17 on the melanogenesis in the B16 melanoma cells
      induced with alpha-melanocyte-stimulating hormone (alpha-MSH), 13 compounds (1,
      3, 4, 6-14, and 17) exhibited marked inhibitory effects with 34-49% reduction of
      melanin content at 100 muM with no or almost no toxicity to the cells (91-116% of
      cell viability at 100 microM).

PMID- 20032600
TI  - Tissue engineering in endodontics.
AB  - Tissue engineering is the science of design and manufacture of new tissues to
      replace impaired or damaged ones. The key ingredients for tissue engineering are
      stem cells, the morphogens or growth factors that regulate their differentiation,
      and a scaffold of extracellular matrix that constitutes the microenvironment for
      their growth. Recently, there has been increasing interest in applying the
      concept of tissue engineering to endodontics. The aim of this study was to review
      the body of knowledge related to dental pulp stem cells, the most common growth
      factors, and the scaffolds used to control their differentiation, and a clinical
      technique for the management of immature non-vital teeth based on this novel
      concept.

PMID- 20032601
TI  - Comparison of immunohistochemical markers between adenoid cystic carcinoma and
      polymorphous low-grade adenocarcinoma.
AB  - Adenoid cystic carcinoma (AdCC) and polymorphous low-grade adenocarcinoma (PLGA)
      have several common histological and clinicopathological features that may create
      diagnostic difficulties. In this study, 10 AdCCs, 8 PLGAs, and 5 normal minor
      salivary glands as a control group were selected. Sections prepared from each
      tumor were stained using the streptavidin-biotin system for seven marker
      antigens: carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA),
      muscle-specific actin (MSA), vimentin, S100, p53, and Ki-67. Data analysis showed
      high expression of CEA, MSA and Ki-67 in AdCCs compared with PLGAs, although CEA
      expression was limited to luminal cells. Ki-67 was expressed in both luminal and
      non-luminal cells and MSA only in non-luminal cells. Vimentin and S100 showed
      stronger expression in PLGAs, the expression of vimentin was more noticeable,
      being focal and widespread. The immunoreactivities of EMA and P53 were not
      helpful for distinguishing between the two tumors, although the EMA expression
      pattern in AdCCs was limited to luminal cells, whereas it was present in both
      luminal and non-luminal cells in PLGAs. Thus, immunohistochemistry can be helpful
      for differential diagnosis of AdCC and PLGA, particularly that for CEA, vimentin,
      and Ki-67.

PMID- 20032602
TI  - Dental anxiety and salivary cortisol levels before urgent dental care.
AB  - Dental anxiety is still prevalent, despite advances in treatment, and affects the
      utilization of health care services. The purpose of this cross-sectional study
      was to determine if patients with different degrees of dental anxiety and pain
      undergoing emergency dental care have different stress reactions as measured by
      salivary cortisol. Seventy three patients completed the modified dental anxiety
      scale (MDAS), and described any previous dental traumatic experience. Their socio
      demographic characteristics were also recorded. They also rated pain intensity on
      a 100 mm visual analogue scale (VAS). A saliva sample was collected before the
      procedure, and analyzed by enzyme immunoassay. Thirty patients were dentally
      anxious and forty one complained of pain. In this sample, dental anxiety was not
      related to gender, age, educational level and family income; however, a previous
      traumatic event was related to dental anxiety. There was no association between
      salivary cortisol concentrations and gender or dental anxiety. Patients with pain
      showed higher cortisol levels. When gathering patient information, the dentist
      should note patients' negative dental experiences in order to provide more
      effective, less traumatic treatment.

PMID- 20032603
TI  - Studies of palatine rugae and interferon regulatory factor 6 variations in a
      group of families with sporadic hypodontia.
AB  - Irf6 (interferon regulatory factor 6) is expressed in tooth buds and palatine
      rugae during development in the mouse. Here we report the first study to
      investigate whether IRF6 variation is associated with palatine rugae patterns in
      a population with sporadic tooth agenesis. Fifty-two individuals with sporadic
      tooth agenesis and their parents were studied. Palatine rugae were scored from
      casts available for a subset of 38 families. DNA samples were obtained from whole
      blood or saliva samples. Genotyping was performed using TaqMan assays. Linkage
      disequilibrium and transmission distortion analyses of the marker alleles were
      performed. Borderline results were obtained for IRF6 genetic variation and having
      primary rugae larger on the right side than on the left (rs20131633, P = 0.07;
      rs642961, P = 0.06) and having fewer than eight primary palatine rugae
      (rs20131623, P = 0.07). However, no specific pattern of tooth agenesis was
      associated with the palatine rugae patterns studied. Our data suggest that IRF6
      may contribute to specific palatine rugae patterns in humans.

PMID- 20032604
TI  - Influence of previous acid etching on dentin bond strength of self-etch
      adhesives.
AB  - The purpose of this study was to investigate the effect of previous phosphoric
      acid etching on the dentin bond strength of single-step self-etch adhesive
      systems. Facial surfaces of bovine teeth were wet ground with #600 SiC paper.
      Adhesives were applied with and without previous phosphoric acid etching, and
      light irradiated. Resin composite was bonded to the adherend surface, followed by
      light irradiation and storage in water at 37 degrees C. Four groups (n = 10) were
      made per adhesive system: with and without previous acid etching and with and
      without thermal cycling between 5 degrees C and 55 degrees C for 10,000 cycles.
      Specimens were tested in a shear mode at a crosshead speed of 1.0 mm/min. Two-way
      ANOVA and Tukey HSD test at a level of 0.05 were performed. The changes in dentin
      bond strengths were different among the adhesive systems tested. In all
      experimental conditions of this study, the dentin bond strength decreased or
      remained unchanged with previous acid etching. From the results of this study,
      previous acid etching might not be acceptable for increasing dentin bond strength
      of the single-step self-etch adhesive systems.

PMID- 20032605
TI  - Oral health impact profile and prosthetic condition in edentulous patients
      rehabilitated with implant-supported overdentures and fixed prostheses.
AB  - The complexity of rehabilitation for totally edentulous patients makes it
      necessary to devise treatment strategies that meet the patients' expectations in
      terms of function, esthetic, psychological, and social aspects. The aim of this
      study was to i) compare the satisfaction of edentulous patients who had been
      rehabilitated with implant-supported overdentures and fixed prostheses in the
      mandible, and ii) assess the technical aspects of the prostheses in relation to
      patient satisfaction. This was a cross-sectional study involving 30 patients, 15
      of whom had been rehabilitated with implant-supported overdentures and 15 who had
      been treated with fixed prostheses. The patients answered the OHIP-EDENT
      questionnaire, validated for the Brazilian Portuguese language, to assess
      satisfaction. Also, patients underwent clinical examination to assess the
      condition of their prostheses. Statistical analysis using the Mann-Whitney U-test
      revealed no significant differences in satisfaction between patients with
      overdentures and those with fixed prostheses. Likewise, Fisher's exact test
      demonstrated no significant differences in patient satisfaction concerning the
      condition of the prostheses as evaluated by the prosthodontist. It was concluded
      that both types of prostheses were perceived as being equally satisfactory by
      edentulous patients, and that the condition of the prostheses did not influence
      individual satisfaction in terms of rehabilitation.

PMID- 20032606
TI  - Perceived need for and utilization of dental care in Indonesia in 2006 and 2007:
      a secondary analysis.
AB  - The objective of this study was to describe the self-perceived need for and
      utilization of dental care in Indonesia. Using secondary data from the Indonesian
      National Socio Economic Survey, 2006 (n = 1,107,594) and 2007 (n = 1,167,019), we
      estimated the proportion of perceived need for and utilization of dental care.
      Descriptive and multivariate logistic regression analyses were used to describe
      the perceived need for and utilization of dental care in different demographic
      and socioeconomic groups (based on age, gender, living standards, residence,
      macroregions, and health insurance entitlement) in Indonesia. Approximately only
      2.33% and 2.28% of Indonesians reported a perceived need for dental care in 2006
      and 2007, respectively. Dental care utilization increased from 0.65% in 2006 to
      0.84% in 2007. Additionally, unmet need decreased from 72.04% in 2006 to 63.13%
      in 2007. Logistic regression analysis indicated that respondents aged 30-44
      years, who were wealthy, and were insured had higher odds ratios in perceiving
      need for and utilizing dental treatment. The perceived need for and utilization
      of dental care among Indonesians was found to be low, and was influenced by
      various demographic socioeconomic factors.

PMID- 20032607
TI  - VEGFR2 expression and relationship between tumor neovascularization and
      histologic characteristics in oral squamous cell carcinoma.
AB  - Neovascularization in the stroma of a tumor plays an important role in tumor
      growth and the establishment of metastases. The present study examined the
      immunohistochemical expression of vascular endothelial growth factor receptor 2
      (VEGFR2) in 34 cases of oral squamous cell carcinoma (OSCC). Moreover, the
      relationships between parameters of tumor neovascularization (count of VEGFR2
      positive [+] cells and total size of vessel lumen [TSVL]) and those of histology
      (differentiation type and mode of invasion) were analyzed statistically.
      Immunohistochemical expression of VEGFR2 was localized in stromal cells at the
      tumor invasive front. The VEGFR2+ cell count around poorly differentiated tumors
      was significantly higher than that around well differentiated tumors (P = 0.032,
      one-way ANOVA). The TSVL around the well differentiated type was found to be
      significantly larger than that around the poorly or moderately differentiated
      type (P < 0.001, respectively; one-way ANOVA). With regard to the mode of
      invasion, the TSVL was significantly larger for lower-grade (Grades 1+2) than for
      higher-grade (Grades 3+4) tumors (P < 0.001, unpaired t-test). On the basis of
      our results, we suggest that vascular development at the invasive front of OSCC
      is governed by the following factors: the tumor cells themselves may induce
      hemangiogenesis in the adjoining stromal tissue; hemangiogenic activity is higher
      when parenchymal intercellular adhesion is looser and when the parenchymal area
      exposed to the stroma is greater; and the rate of blood flow is higher when
      parenchymal intercellular adhesion is tighter and parenchymal nests are larger.

PMID- 20032608
TI  - Linear measurements to determine working length of curved canals with fine files:
      conventional versus digital radiography.
AB  - This in vitro study compared conventional and digital radiographic linear
      measurements to determine the working length (WL) of curved canals with fine
      endodontic files. In total, 30 mesiobuccal root canals in molars were measured
      with a #06 K-file to a length 1 mm short of the apical foramen (WL1). Teeth were
      mounted in plastic blocks and standardized periapical radiographs were obtained
      by conventional and digital (Digora Optime) radiographic methods with #06, #08
      and #10 K-files positioned in WL1. Two independent and calibrated examiners
      performed the conventional measurements with a millimeter ruler, from the file
      stop to the file tip (WL2). For the digital images, examiners used the linear
      measurement tool on the Digora software, in original mode (WL3). For comparison
      of WL1, WL2 and WL3, the Wilcoxon test (P < 0.05) was applied and the
      reproducibility of the measurements was assessed. There was no statistically
      significant difference between Wl2 and Wl3 for #06, #08 and #10 K-files (P =
      0.341, 0.641 and 0.232, respectively), with an acceptable level of interexaminer
      agreement. The measurements of Wl2 and Wl3 were significantly (P < 0.05) larger
      than those of WL1. No difference was observed among the linear measures obtained
      with either radiographic method, which showed higher WL values than the direct
      measurements.

PMID- 20032609
TI  - A randomized phase III prospective trial of bethanechol to prevent mucositis,
      candidiasis, and taste loss in patients with head and neck cancer undergoing
      radiotherapy: a secondary analysis.
AB  - The aim of this study was to determine the impact of bethanechol administration
      concomitant to radiotherapy (RT) on oral mucositis, candidiasis and taste loss.
      We performed a secondary analysis of a previously conducted prospective
      randomized trial which evaluated the effect of bethanechol on salivary gland
      dysfunction before, during, and after RT for head and neck cancer (HNC), in
      comparison to artificial saliva. Mucositis, candidiasis and taste loss were
      analyzed in 36 patients. Mucositis was scored using the World Health Organization
      (WHO) method; candidiasis was diagnosed by means of clinical examination, whereas
      taste loss was assessed by the patients' subjective report of absence of taste.
      No significant differences were observed between groups in relation to frequency
      and severity of mucositis or frequency of candidiasis and taste loss. In
      conclusion, bethanechol does not appear to reduce the incidence of mucositis,
      candidiasis, and taste loss when administered during RT.

PMID- 20032610
TI  - Secretory proteins in the saliva of children.
AB  - The protein composition of oral fluid is modulated by environmental factors and
      physiological states, i.e. chemical, mechanical and pharmacologic stimuli,
      pathologic conditions, and psychological stress. Secretory protein concentrations
      in samples of whole saliva (WS) from children were measured and the results were
      subjected to statistical analysis. Protein expression was determined using
      electrophoresis and Western blotting. Protein profiles of children were
      significantly different from those of adults (n = 50, P < 0.05). All samples of
      saliva from children contained a group of high-molecular-weight (>90 kDa)
      proteins, whereas fewer than 5% of samples from adults had comparable bands. The
      ratio of the regulatory subunits (RII) of type II protein kinase A (an enzyme
      that regulates secretion) to total protein was stable in children's saliva, but
      variable in saliva from adults. Alpha amylase (alpha-amylase), an enzyme that
      digests carbohydrates, was less degraded in WS of children than in that of
      adults. Gingival crevicular fluid of both children and adults did not contain
      alpha-amylase or RII. No significant gender-based differences were found, but
      Caucasian children had higher salivary protein levels than children with an
      African background. Saliva collection is rapid, painless, non-invasive,
      economical, and yields findings that are reproducible. Objective, biochemical
      monitoring of secretory proteins in oral fluid of children may reveal responses
      to stressful stimuli.

PMID- 20032611
TI  - Odontogenic cysts: a clinicopathological study of 507 cases.
AB  - The purpose of this study was to determine the prevalence of odontogenic cysts at
      the Pernambuco School of Dentistry - Universidade de Pernambuco (Brazil) and
      compare this prevalence with other international studies. Data for the study were
      obtained from reports of patients diagnosed with odontogenic cysts between 1992
      and 2007. Case records of patients who fit the Histological Classification of the
      World Health Organization (2005) were included. The following variables were
      analyzed: gender, age group, anatomical location, histological type and ethnic
      background. Odontogenic cysts accounted for 9.94% of all lesions biopsied
      throughout the study period. Mean patient age was 28.9 years and 57.6% of the
      patients were males (P > 0.05). Radicular cyst was the most prevalent
      histological type (52.2%), followed by dentigerous cyst (30.7%). Regarding ethnic
      background, 41.8 % of the patients were of African descent, followed by
      Caucasians and other ethnic groups (P > 0.05). The mandible was the most
      prevalent site of the lesions (56%). Odontogenic cysts appear to have a distinct
      predilection for the male gender, the second and third decades of life (P < 0.05)
      and are more frequent in the mandible. The removal of odontogenic keratocysts
      from the new WHO classification has not altered the order of the most prevalent
      cysts in the maxillofacial complex.

PMID- 20032612
TI  - Age-related changes in crown and root length in Sri Lankan Sinhalese.
AB  - Exploration of the relationship between tooth dimensions, body size, and age is
      important in paleontology, forensic odontology and aesthetic dentistry. It is
      reasonable to speculate that tooth length is associated with stature since teeth
      contribute to facial height. This study aimed to determine whether there was an
      association between tooth length and stature and age in a sample of Sri Lankan
      Sinhalese. Extracted teeth of adults, whose age, sex and standing height were
      known, were used for measurements. The total tooth length (TTL), crown length
      (CL) and root length (RL) of permanent maxillary central (68) and lateral (67)
      incisors were measured using a caliper. Statistical analyses were performed with
      the software MINITAB version 14.0 (Minitab Inc, USA). Mean age and standing
      height were 47.81 yr and 152.15 cm, respectively. There was no significant
      correlation between stature and tooth lengths of incisors. However, age was found
      to have a significant correlation with RL, (r = 0.26, P < 0.05) and CL (r = 
      0.28, P < 0.05). Absence of an association between tooth length and stature
      indicated that the genetic linkage between tooth size and stature was weak,
      suggesting that determination of stature from tooth lengths is unwarranted. The
      association between tooth length and age indicates the importance of root length
      in age determination.

PMID- 20032613
TI  - Assessment of the apical seal of root canals using different filling techniques.
AB  - The aim of this study was to investigate the apical leakage of roots filled by
      three different gutta-percha techniques: lateral condensation, Tagger's hybrid
      and E&Q Master. Forty-two extracted single-rooted teeth were used. The coronal
      part of each tooth was removed and the root received biomechanical preparation
      using a 60-K file. The roots were randomly divided into three groups according to
      the technique of filling the root canal: Group I, lateral condensation; Group II,
      Tagger's hybrid; Group III, E&Q Master. The roots were submitted to dye leakage
      test with Rhodamine B for 7 days, using vacuum during the initial 30 min. The
      teeth were sectioned longitudinally and the leakage was measured in a linear
      fashion from apex to crown. Statistical analysis indicated that lateral
      condensation and E&Q Master techniques showed lower leakage than Tagger's
      technique (P = 0.0016). However, statistically no difference was found between
      lateral condensation and E&Q Master system techniques.

PMID- 20032614
TI  - Sealing ability of mineral trioxide aggregate and Portland cement for furcal
      perforation repair: a protein leakage study.
AB  - The purpose of this study was to compare the sealing ability of gray mineral
      trioxide aggregate (GMTA), white MTA (WMTA), and both white and gray Portland
      cement as furcation perforation repair materials. A total of 120 human mandibular
      first molars were used. After root canal obturation and preparation of furcal
      perforations the specimens were randomly divided into four groups of 25 teeth
      each. In groups A, B, C, and D furcation perforations were filled with WMTA,
      GMTA, white Portland cement, and type II Portland cement, respectively. Ten teeth
      were used as positive controls with no filling materials in the perforations and
      10 teeth with complete coverage with two layers of nail varnish were used as
      negative controls. A protein leakage model utilizing 22% bovine serum albumin
      (BSA) was used for evaluation. Leakage was noted when color conversion of the
      protein reagent was observed. The controls behaved as expected. Leakage was found
      in the samples from group A (WMTA), group B (GMTA), and in the two other groups
      (white and gray Portland cement). There were no statistically significant
      differences between GMTA and WMTA or white and gray Portland cement, but
      significant differences were observed between the MTA groups and the Portland
      cement groups. It was concluded that Portland cements have better sealing ability
      than MTA, and can be recommended for repair of furcation perforation if the
      present results are supported by other in vivo and in vitro studies.

PMID- 20032615
TI  - Effects of sonic scaling on the surface roughness of restorative materials.
AB  - The surface roughness of dental restorative materials has a crucial effect on the
      health of dental and periodontal tissues as well as for the longevity of
      restorations. In this study we tested a glass ionomer restorative cement, two
      nanohybrid resin composites, a flowable resin composite and a silorane-based
      composite. Twenty cylindrical specimens of each material were prepared, cured,
      polished and instrumented with a sonic scaler (Alegra ST ZE-55 RM W&H, Austria).
      The mean surface roughness was recorded using a profilometer (SJ-201, Mitutoyo,
      Japan) at three stages: before scaling, after scaling and after re-polishing.
      Additional specimens were analyzed by scanning electron microscopy and back
      scattered imaging. Data were examined statistically by analysis of variance
      (ANOVA) and post-hoc tests at a level of significance of P < 0.05. The
      profilometric measurements and the SEM evaluation showed that, in most of the
      materials tested, the surface roughness was significantly increased after sonic
      instrumentation. After re-polishing the specimens, the roughness values were
      decreased. Periodontal scaling should include polishing of restorations in order
      to overcome alterations in surface roughness.

PMID- 20032616
TI  - Measurement of cerebral reactive hyperemia at the initial post-ischemia
      reperfusion stage under normothermia and moderate hypothermia in rats.
AB  - Inhibition of the initial events occurring immediately after ischemia-reperfusion
      seems to be beneficial for reducing the extent of subsequent chronic neuronal
      cell injury. We investigated the effects of moderate hypothermia (32 degrees C)
      commencing 30 min before ischemia on reactive hyperemia by measuring cerebral
      blood flow (CBF) with a laser-Doppler flowmeter at the initial ischemia
      reperfusion stage (60 min) following 10 min of global cerebral ischemia in rats.
      In normothermia, CBF was increased to approximately 240% and decreased
      thereafter, although it remained at approximately 150% after 60 min of ischemia
      reperfusion. In contrast, hypothermia increased CBF to more than 270% after
      ischemia-reperfusion, then recovered to the basal level within 30 min. The period
      of reactive hyperemia under normothermia tended to be shortened by pre
      administration of an NMDA antagonist, in a manner similar to hypothermia.
      Furthermore, hypothermia inhibited the presence of cells with caspase-3-like
      immunoreactivity in the hippocampal CA1 sector after 8 h of ischemia-reperfusion.
      Our findings indicate that hypothermia tends to shorten the period of reactive
      hyperemia during the initial ischemia-reperfusion stage. This phenomenon may be
      partly associated with activation of NMDA receptors and a beneficial effect of
      hypothermia in resisting progression of the neurotoxic cascade in the first 8 h
      after ischemia-reperfusion.

PMID- 20032617
TI  - Morphology of the cemento-enamel junction in premolar teeth.
AB  - The present study attempted to describe the distribution of the mineralized
      tissues that compose the cemento-enamel junction, with respect to both the
      different types of permanent premolars of males and females and the various
      surfaces of individual teeth. The cervical region of ground sections of 67
      premolars that had been extracted for orthodontic reasons were analyzed using
      transmitted light microscopy to identify which of the following tissue
      interrelationships was present at the cemento-enamel junction: cementum
      overlapping enamel; enamel overlapping cementum; edge-to-edge relationship
      between cementum and enamel; or the presence of gaps between the enamel and
      cementum with exposed dentin. An edge-to-edge interrelation between root cementum
      and enamel was predominant (55.1%). In approximately one-third of the sample,
      gaps between cementum and enamel with exposed dentin were observed. Cementum
      overlapping enamel was less prevalent than previously reported, and enamel
      overlapping cementum was seen in a very small proportion of the sample. In any
      one tooth, the distribution of mineralized tissues at the cemento-enamel junction
      was irregular and unpredictable. The frequency of gaps between enamel and
      cementum with exposure of dentin was higher than previously reported, which
      suggests that this region is fragile and strongly predisposed to pathological
      changes. Hence, this region should be protected and carefully managed during
      routine clinical procedures such as dental bleaching, orthodontic treatment, and
      placement of restorative materials.

PMID- 20032618
TI  - Shear bond strength between an indirect composite veneering material and zirconia
      ceramics after thermocycling.
AB  - The present study evaluated the shear bond strength between an indirect composite
      material and zirconium dioxide (zirconia) ceramics after thermocycling. A total
      of 80 zirconia (Katana) discs were divided into five groups and primed with one
      of following agents: All Bond 2 Primer B (ABB), Alloy Primer (ALP), AZ Primer
      (AZP), Estenia Opaque Primer (EOP), and Porcelain Liner M Liquid A (PLA). An
      indirect composite material (Estenia C&B) was then bonded to the primed zirconia.
      One-half of the specimens (n = 8) in each group were stored in distilled water at
      37 degrees C for 24 h, and the remaining eight specimens were thermocycled 5,000
      times before shear bond strength testing. Mean bond strengths before
      thermocycling varied from 10.1 to 15.6 MPa; bond strengths after thermocycling
      ranged from 4.3 to 17.6 MPa. The ALP group had the highest strengths after
      thermocycling; there were no significant differences among the PLA, AZP, and EOP
      groups. The bond strength values for PLA, AZP, EOP, and ALP did not decrease with
      thermocycling. The application of an acidic functional monomer containing
      carboxylic anhydride (4-META), phosphonic acid (6-MHPA), or phosphate monomer
      (MDP) provided durable bond strength between Estenia C&B indirect composite and
      Katana zirconia.

PMID- 20032619
TI  - Associations among distributions of dental postgraduate residents, dentists and
      clinical training facilities in Japan.
AB  - The purpose of this study was to evaluate the correlation and distribution of
      dental postgraduate residents, dentists and clinical training facilities in each
      prefecture to analyze the regional distribution and supply of dentists in Japan.
      The results were also compared with referential data for medicine. The
      coefficient of correlation between the dentist index and dental postgraduate
      resident index was r = 0.76 (P < 0.001) in 2006. The distribution (coefficient of
      variation) was greatest for the dental postgraduate resident index. The numbers
      of dentists per 100,000 population in prefectures with dental colleges were
      significantly higher in 1986, 1996 and 2006 for each comparison (P < 0.001).
      Coefficients of correlation between dentist index and dental postgraduate
      resident index were r = 0.65 (P < 0.01) in prefectures with dental colleges and r
      = 0.11 in those without dental colleges in 2006. The prefectures with high level
      of numbers of cooperative-type clinical training facilities had dental colleges.

PMID- 20032620
TI  - Sebaceous adenoma of the submandibular gland: a case report.
AB  - Sebaceous adenoma of the salivary gland is a rare tumor comprising 0.1% of all
      salivary gland neoplasms and less than 0.5% of salivary adenomas. Histologically,
      sebaceous adenomas are benign neoplasms consisting of sebaceous cells arranged in
      nests forming acinar and duct-like structures. Oncocytic metaplasia may also
      occur in some areas. We describe a case of sebaceous adenoma in the submandibular
      gland. Under a presumptive diagnosis of sialadenitis/sialolithiasis, the patient
      was administered multiple courses of antibiotics; however, these were not
      effective. Excisional biopsy resulted in a diagnosis of sebaceous adenoma. A 1
      year follow-up showed no recurrence.

PMID- 20032621
TI  - A case of personal identification due to detection of rare DNA types from seminal
      stain.
AB  - Following a rape incident in an apartment in Japan, we were requested to perform
      a DNA analysis on a body fluid stain left on a bath towel to determine whether it
      could be attributed to the suspect. The acid phosphatase and prostatic-specific
      antigen tests confirmed it to be a seminal stain. Based on the DNA analysis by
      autosomal and Y-chromosome short tandem repeat (STR) systems, no inconsistency
      was found with the profile of the suspect with African ancestry. In this case,
      allele 21 of DYS390 at the Y-STR locus was examined, as it is reported to have a
      distinctly lower frequency in the Japanese population. Furthermore, the haplotype
      combinations of Y-STR at the DYS389I, DYS389II and DYS390 loci are powerful for
      personal identification, as these have not yet been found in the Japanese
      population.

PMID- 20032622
TI  - Orthodontic extrusion with palatal circumferential supracrestal fiberotomy
      improves facial gingival symmetry: a report of two cases.
AB  - Discrepancy in the labial gingival margin of the maxillary incisors poses a major
      aesthetic problem. Orthodontic extrusion can improve the aesthetic problem caused
      by gingival margin levels before restoration. In these case reports, orthodontic
      extrusion was performed with palatal circumferential supracrestal fiberotomy for
      improving the discrepancy of the labial gingival margin. Two years
      postoperatively, the position of the tooth and gingival margin remained stable.
      Orthodontic extrusion with palatal circumferential supracrestal fiberotomy was
      effective in improving the discrepancy of the labial gingival margin of maxillary
      incisors.

PMID- 20032623
TI  - Thyroid tissue as a submandibular mass: a case report.
AB  - Ectopic thyroid gland is a rare phenomenon that appears most frequently in the
      cervical midline and very rarely in other sites such as the submandibular region.
      This article reports a painless, non-tender and firm thyroid tissue mass in the
      right submandibular region of a 29-year-old female patient. Physicians should
      consider ectopic thyroid tissue as a differential diagnosis of submandibular
      swellings and be aware that this ectopic gland is the only functional thyroid
      tissue in 70% of cases.

PMID- 20032624
TI  - Removal of infected nonresorbable hydroxyapatite graft material in recurrent
      periodontitis: a report of two cases.
AB  - Long-term studies have indicated that alloplastic bone grafts composed of
      nonresorbable hydroxyapatite (NHA) are clinically stable and safe. However, our
      previous report suggested that NHA grafts may be an etiological factor for
      recurrent periodontitis in the absence of supportive periodontal treatment (SPT).
      We removed infected NHA from the root surface by flap surgery in two cases of
      recurrent periodontitis. After removal of the infected NHA, the inflammation
      subsided in these cases and they were clinically stable for several years.

PMID- 20032625
TI  - Evaluation of Myanmar medicinal plant extracts for antitrypanosomal and cytotoxic
      activities.
AB  - Current chemotherapeutic options for African trypanosomiasis in humans and
      livestock are very limited. In the present study, a total of 71 medicinal plant
      specimens from 60 plant species collected in Myanmar were screened for
      antitrypanosomal activity against trypomastigotes of Trypanosoma evansi and
      cytotoxicity against MRC-5 cells in vitro. The methanol extract of dried rootbark
      of Vitis repens showed the highest antitrypanosomal activity with IC(50) value of
      8.6 +/- 1.5 microg/ml and the highest selectivity index of 24.4. The extracts of
      Brucea javanica, Vitex arborea, Eucalyptus globulus and Jatropha podagrica had
      also remarkable activity with IC(50) values and selectivity indices in the range
      of 27.2-52.6 microg/ml and 11.4-15.1 respectively.

PMID- 20032626
TI  - Development of reverse transcription-loop-mediated isothermal amplification (RT
      LAMP) assay for detection of avian influenza viruses in field specimens.
AB  - Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is an
      established gene amplification method for rapid diagnosis of various infectious
      diseases. In order to detect avian influenza viruses, particularly in field
      specimens, specific primers targeting the matrix gene were designed. Thirty-four
      virus samples, including isolates from wild and domestic avian hosts belonging to
      various geographical areas, were used to confirm the validity of the primers. All
      samples were confirmed to be positive in less than 1 hr. The RT-LAMP assay was
      also able to detect avian influenza virus in the various field samples, such as
      swabs, tissues, and feces. These results indicate that the developed RT-LAMP
      assay with uniquely designed primers is potentially useful in comprehensive avian
      influenza surveillance.

PMID- 20032627
TI  - Changes in the gene expression and enzyme activity of hepatic cytochrome P450 in
      juvenile Sprague-Dawley rats.
AB  - The developmental changes in the hepatic cytochrome P450 (CYP) content, mRNA
      expression of 12 hepatic CYP subtypes, and the enzyme activities of 5 hepatic CYP
      subfamilies in rats were investigated using non-treated male and female Sprague
      Dawley rats of ages postnatal day (PD) 4, 16, 30 and 8 and 12 weeks. The hepatic
      proliferation kinetics was also determined by using the phospho-histone H3 (p
      histon)-labeled hepatocyte index. The developmental changes in the enzyme
      activities of hepatic expression of CYP1A and CYP3A in rats were similar to those
      in humans, although there is no fetal-neonatal dominant CYP3A subtype in rat
      livers unlike human CYP3A7. On the other hand, the developmental pattern of
      expression of the CYP2C subfamily differed between humans and rats. Enzyme
      activity and mRNA expression of each hepatic CYP subtype in rats on PD 30 was
      similar to that after 8 weeks of age, except in the case of sex-dependent CYP
      subtypes. The p-histon-labeled hepatocyte index was approximately 10-fold higher
      in PD 30 rats than in 8-week-old rats. Therefore, the livers of juvenile rats,
      which have high hepatocellular proliferation activity and a sufficient amount of
      metabolic enzymes such as CYP, may be more sensitive to the cytotoxic and
      carcinogenic effects of chemicals than the livers of adult rats. Thus, our
      results on developmental difference of hepatic CYPs in juvenile rats are useful
      to identify underlying age-dependent susceptibility of chemical-induced toxicity,
      and to understand developmental change of chemical disposition.

PMID- 20032628
TI  - Effect of embryo transfer following artificial insemination (ETFAI) on
      reproductive performance in dairy cows in South-Western Japan.
AB  - In order to improve the reproductive performance during the summer period, embryo
      transfer (ET; Japanese black embryo) following artificial insemination (AI;
      Holstein semen: ETFAI) was conducted in dairy cows in south-western Japan (n=56).
      The conception rate was improved in cows with ETFAI compared with conventional
      AI, which served as the control (n=195; 30.4% vs. 13.8%, P<0.01). However, higher
      fetal loss was observed in ETFAI compared with the controls (38.1% vs. 7.4%,
      P<0.05). Four cases of twin pregnancy resulted in 2 singletons and a set of
      twins. There was no difference in the plasma progesterone level on d0 or d7
      (d0=AI), but rather lower rectal temperature was observed on d7 or d8 (38.7
      degrees C vs. 39.4 degrees C and 38.8 degrees C vs. 39.1 degrees C, P<0.05) in
      pregnant cows compared with those that were open. ETFAI could improve
      reproductive performance in dairy cows during the summer period in south-western
      Japan.

PMID- 20032629
TI  - Type I familial visceral myopathy presenting with CT findings of superior
      mesenteric artery syndrome in an adolescent.

PMID- 20032631
TI  - Gastrointestinal sarcoidosis in an adolescent presenting with hemorrhage from a
      bleeding duodenal ulcer.

PMID- 20032630
TI  - Post-ERCP pancreatitis in pediatric patients.
AB  - OBJECTIVES: Pancreatitis is a known complication of endoscopic retrograde
      cholangiopancreatography (ERCP). Our aim was to assess the prevalence and
      severity of ERCP-associated pancreatitis using established criteria. MATERIALS
      AND METHODS: Retrospective review of patients younger than 18 years undergoing
      ERCP complicated by post-ERCP pancreatitis defined by the 1991 consensus
      statement. Patients with chronic pancreatitis were studied separately using
      modified criteria. Risk factors for post-ERCP pancreatitis were analyzed.
      RESULTS: Three hundred forty-three ERCPs were performed in 224 patients. Two
      hundred seventy-six ERCPs were performed in patients without chronic
      pancreatitis, 7 of which were complicated by post-ERCP pancreatitis (prevalence
      2.5%). Patients undergoing diagnostic-only ERCP were less likely to develop post
      ERCP pancreatitis (P<0.01). Sixty-seven procedures were performed on patients
      with chronic pancreatitis; 10 developed postprocedure pain requiring or
      prolonging hospitalization (prevalence 14.9%). Pancreatic duct stenting was a
      risk factor for post-ERCP pain in this subset of patients (P=0.02). CONCLUSIONS:
      The prevalence of post-ERCP pancreatitis is low-2.5% excluding patients with
      chronic pancreatitis and 4.96% overall. Therapeutic procedures and the presence
      of chronic pancreatitis are risk factors for post-ERCP pancreatitis.

PMID- 20032632
TI  - Primary immunodeficiency disease: a model for case management of chronic
      diseases.
AB  - PURPOSE/OBJECTIVES: Patient-centered chronic care management is a new model for
      the management of rare chronic diseases such as primary immunodeficiency disease
      (PIDD). This approach emphasizes helping patients become experts on the
      management of their disease as informed, involved, and interactive partners in
      healthcare decisions with providers. Because only a few patients are affected by
      rare illnesses, these patients are forced to become knowledgeable about their
      disease and therapies and to seek treatment from a healthcare team, which
      includes physicians and nurse specialists who are equipped to manage the
      complexity of the disease and its comorbidities. Importantly, therapy for PIDD
      can be self-administered at home, which has encouraged the transition toward a
      proactive stance that is at the heart of patient-centered chronic care
      management. We discuss the evolution of therapy, the issues with the disease, and
      challenges with its management within the framework of other chronic disease
      management programs. Suggestions and rationale to move case management of PIDD
      forward are presented with the intent that sharing our experiences will improve
      process and better manage outcomes in this patient population. PRIMARY PRACTICE
      SETTINGS: The patient-centered model for the management of PIDD is applicable to
      the primary care settings, where nurse case managers assist patients through
      education, support them and their families, and facilitate access to community
      resources in an approach, which has been described as "guided care." The model
      also applies specifically to immunology centers where patients receive treatment
      or instruction on its self-administration at home. FINDINGS/CONCLUSIONS: Patient
      centered management of PIDD, with its emphasis on full involvement of patients in
      their treatment, has the potential to improve compliance with treatment, and thus
      patient outcomes, as well as patients' quality of life. IMPLICATIONS FOR CASE
      MANAGEMENT: The patient-centered model expands the traditional model of chronic
      disease management, which relies on evidence-based medicine, provider expertise,
      clinical information systems, and patient education. This approach supports
      patient self-management with strategies that empower and prepare them for their
      role as expert patients.

PMID- 20032633
TI  - Small cell tumors of bone.
AB  - Bone tumors are fortunately rare, but small cell tumors of bone are a relatively
      common subset of these lesions. They comprise of a diverse group of primary and
      metastatic neoplasms in both children and adults. The most common small cell
      tumors of bone include Ewing sarcoma/primitive neuroectodermal tumor, small cell
      osteosarcoma, multiple myeloma, lymphoma, leukemia, neuroblastoma,
      rhabdomyosarcoma, and Langerhans cell histiocytosis. Although each entity has its
      distinctive features, the differential diagnosis of this group of tumors is still
      challenging because they are all "small, blue, and round cell tumors",
      histologically. The correct diagnosis of small cell tumors of bone depends on an
      evaluation of clinical, radiologic, pathologic, and genetic features. Patients'
      age and sex are very important, as are the signs and symptoms at presentation.
      Radiologically, which bone is involved, the specific portion of the bone
      (epiphysis, metaphysis, or diaphysis; cortex vs. medulla) involved, and the
      radiographic manifestations (lytic, blastic, or mixed lytic and blastic) are also
      often critical parameters for the diagnosis. In recent years, with a better
      understanding of the molecular and cytogenetic background of several small cell
      tumors, more accurate diagnoses have been supported by the clinicopathologic
      criteria and by a panel of immunohistochemical studies. In this review we will
      provide an overview of the clinical, radiologic, pathologic, and genetic
      characteristics of these tumors.

PMID- 20032634
TI  - Histiocytic disorders of the lung.
AB  - Histiocytic proliferations involving the lung span a broad spectrum. Some
      proliferations are primary; others represent a histiocytic response secondary to
      conditions in which there may be isolated lung involvement or the lung may be
      involved as part of a systemic process. Primary histiocytic lung disorders,
      particularly those of uncertain histogenesis are a heterogeneous and intriguing
      group of disorders. Although they have been the focus of attention by clinicians
      and pathologists alike, much is unknown about their etiopathogenesis. Owing to
      this uncertainty, our understanding of these processes is in a state of flux, and
      is likely to change as more information is brought to light. This review will
      focus on pulmonary histiocytic proliferations of uncertain histogenesis. Other
      histiocytic lesions will be dealt with in brief.

PMID- 20032636
TI  - An update on lung cancer staging.
AB  - The staging committee of the International Association for the Study of Lung
      Cancer has recently published, in collaboration with the International Union
      Against Cancer and the American Joint Committee on Cancer, the recommendations
      for the upcoming 7th edition of the tumor, node, metastasis classification and
      staging manual. This article reviews the changes in criteria for the tumor, node,
      metastasis components and discusses the issues that will be faced by pathologists
      when examining lung cancer specimens, including recommendations for tumor
      measurement, differentiation of multiple primary tumors versus metastases, and
      visceral pleural invasion.

PMID- 20032635
TI  - KRAS mutation testing in human cancers: The pathologist's role in the era of
      personalized medicine.
AB  - A number of studies have shown that although antiepidermal growth factor receptor
      (EGFR) monoclonal antibodies are effective treatments for metastatic colorectal
      cancer (mCRC), only patients with wild-type KRAS tumors derive clinical benefit
      from these therapies. The anti-EGFR monoclonal antibodies panitumumab and
      cetuximab are approved in the United States for treatment of mCRC refractory to
      chemotherapy but are not recommended for use in patients with mutations in KRAS
      codons 12 or 13. Similarly, panitumumab is approved for the treatment of mCRC
      only in patients with wild-type KRAS in Europe and Canada. It is clear that KRAS
      mutational analysis will become an important aspect of disease management in
      patients with mCRC. Consequently, it will be important for pathologists and
      oncologists to develop and agree on standardized KRAS testing and reporting
      procedures to ensure optimum patient care. Pathologists will be central to this
      process because of their crucial role in selecting appropriate tumor specimens
      for testing, choosing the molecular diagnostic laboratory to be used, assisting
      in the selection of a suitable KRAS test, and interpreting the results of KRAS
      mutational analysis. Guidelines for KRAS testing that address these and other
      important points of consideration have recently been proposed in the United
      States and the European Union.

PMID- 20032637
TI  - Giant hypopharyngeal atypical lipomatous tumor.
AB  - The so-called "giant fibrovascular polyps" of the esophagus and hypopharynx
      typically present as sausage-like pedunculated structures that protrude into the
      lumen and cause obstructive symptoms. Most are cured by local resection but they
      may recur. Microscopically, they display an admixture of fibrovascular and
      adipose tissue that is coated by unremarkable squamous mucosa. Here, we report a
      case that had scattered hyperchromatic cells and lipoblasts within the adipose
      tissue component. In other anatomic sites similar appearing lesions have been
      interpreted as pedunculated liposarcomas/atypical lipomatous tumors that are more
      prone to local recurrences than classic giant fibrovascular polyps. Reports of
      dedifferentiation and metastases are lacking thus raising the possibility that
      the cytologic findings in such lesions are degenerative. To confirm our suspicion
      of liposarcomatous differentiation, we performed immunohistochemistry for MDM2
      and p53, 2 markers that are known to be negative in benign lipomatous lesions and
      positive in well-differentiated liposarcomas/atypical lipomatous tumors. The
      scattered atypical hyperchromatic cells and the lipoblasts both exhibited strong
      nuclear staining for both markers and supported the diagnosis of pedunculated
      giant hypopharyngeal atypical lipomatous tumor.

PMID- 20032638
TI  - Oncogene-induced cellular senescence.
AB  - Oncogene-induced senescence (OIS) is a robust and sustained antiproliferative
      response brought about by oncogenic signaling resulting from an activating
      mutation of an oncogene, or the inactivation of a tumor-suppressor gene. The
      pathways mediating OIS are complex and incompletely elucidated but, the
      proliferative arrest involves activation of both the RB and p53 pathways. In
      addition, whereas there are indications that at least in some situations,
      negative feedback loops abolish the increased mitogenic signaling resulting from
      the oncogenic mutations, also an unexpected contribution of interleukin-mediated
      signaling has recently been found. OIS brings about cessation of growth of some
      benign tumors, including melanocytic nevi and several other lesions, including
      pituitary and thyroid adenomas. It protects against progression to cancer, and in
      this way complements oncogene-induced apoptosis. Perhaps, OIS has evolved as an
      alternative to apoptosis especially regarding long-lived cell types that are not
      replaceable in large numbers. Contrary to the earlier belief, OIS is not entirely
      irreversible, at least in some well documented in vitro systems. This means that
      its induction does not entirely eliminate the oncogenic threat resulting from the
      mutated cell. It also means that OIS, or related phenomena that may affect a
      proportion of the tumor cells of some cancers, may have an influence on
      responsiveness to cytotoxic cancer therapies, because OIS is associated with an
      antiapoptosis phenotype.

PMID- 20032639
TI  - The physicians quality reporting initiative: measure development, implementation
      and current procedural terminology coding.
AB  - The Physicians Quality Reporting Initiative (PQRI) was instituted in the latter
      half of 2007. PQRI is a voluntary reporting system in which the aim is to improve
      patient care, whereas at the same time, an eligible practitioner may receive an
      incentive payment for successful participation. Two pathology-specific measures
      were instituted in 2008; 1 for breast cancer reporting and the other for colon
      cancer reporting. In 2009, Current Procedural Terminology Category II code 3250F
      was instituted, which allows proper coding of cases from metastatic sites when
      ICD 9 code and Current Procedural Terminology Category I inclusion criteria are
      met. After the review of the 2007 data obtained from other specialties,
      submission of invalid codes was predominantly attributed to failure to adhere to
      measurement specifications. With increased awareness and experience, the amount
      of invalid code submission will decrease. More performance measures would be
      needed to make the program available to more pathologists. PQRI is thought by
      many to be the first step in transforming to a Pay for Performance Program.

PMID- 20032640
TI  - Paratesticular mesothelioma. Report of a case with comprehensive review of
      literature.
AB  - Paratesticular mesotheliomas are rare tumors with 223 cases described so far. The
      sole plausible causative factor so far ascertained in the pathogenesis of these
      tumors is asbestos, which however is found in only around 30% to 40% of such
      cases. The age range of affected individuals is wide, mostly adults and the
      elderly, but also includes young people and children. The most common presenting
      symptom is either hydrocele of unknown origin or intrascrotal mass. When
      hydrocele is the presenting symptom, these tumors are often clinically overlooked
      and the diagnosis is delayed. Most paratesticular mesotheliomas arise in the
      tunica vaginalis, but primary tumors of the spermatic cord and epididymis are
      also on record. Tumors arising from the peritoneal mesothelium of a hernia sac
      are excluded from this group. The correct diagnosis is almost always made after
      histologic examination of the operative specimen. Immunohistochemistry and
      electron microscopy are always helpful and sometimes necessary tools for
      diagnosis. So far very few cases have been identified or suspected preoperatively
      on cytologic examination. Three clinicopathologic types of malignant
      mesotheliomas of the male genital tract are recognized: diffuse tubulo-papillary
      mesothelioma, well-differentiated papillary mesothelioma, and multicystic
      mesothelioma. The histologic subtypes are almost always pure epithelial or
      biphasic. The differential diagnosis is mainly with serous papillary tumors
      arising from Mullerian vestiges, but several diverse primary or secondary tumors
      also need to be considered. A clinicopathologic evaluation of a case of tunical
      diffuse mesothelioma in a 74-year-old male from the AMR Series is the starting
      point for this general review.

PMID- 20032641
TI  - A new year brings new opportunities.

PMID- 20032642
TI  - Nurses should drive health reform.

PMID- 20032643
TI  - Health care reform.

PMID- 20032644
TI  - Transitional care.

PMID- 20032645
TI  - An abandoned child.

PMID- 20032646
TI  - An abandoned child.

PMID- 20032647
TI  - Being excellent.

PMID- 20032648
TI  - Enteral feeding.

PMID- 20032649
TI  - Four nurses among those slain in Fort Hood shooting.

PMID- 20032650
TI  - The top health care news story of 2009: the economy on life support, health care
      in transition.

PMID- 20032651
TI  - Fighting flu, flu shots, and for flu masks.

PMID- 20032655
TI  - NewsCap: Younger women with early-stage ovarian cancer can keep the healthy ovary
      and uterus.

PMID- 20032659
TI  - The clinical nurse leader.

PMID- 20032660
TI  - Point counterpoint: mandatory flu vaccination for health care workers.

PMID- 20032661
TI  - Point counterpoint: mandatory flu vaccination for health care workers.

PMID- 20032662
TI  - Point counterpoint: mandatory flu vaccination for health care workers.

PMID- 20032664
TI  - Nurses 'leading globally' in Indianapolis.

PMID- 20032665
TI  - Life-support interventions at the end of life: unintended consequences.
AB  - OVERVIEW: Patients and family members often aren't aware that the use of life
      support interventions at the end of life-when the body's systems and organs are
      failing-can have unintended consequences. Nurses need to be knowledgeable and
      able to communicate what they know about those consequences to patients, family
      members, and others on the health care team, leading to better decision making at
      this difficult time.

PMID- 20032668
TI  - Uniting States, sharing strategies: forging partnerships to expand nursing
      education capacity.

PMID- 20032669
TI  - Evidence-based practice: step by step: the seven steps of evidence-based
      practice.
AB  - This is the second article in a new series from the Arizona State University
      College of Nursing and Health Innovation's Center for the Advancement of Evidence
      Based Practice. Evidence-based practice (EBP) is a problem-solving approach to
      the delivery of health care that integrates the best evidence from studies and
      patient care data with clinician expertise and patient preferences and values.
      When delivered in a context of caring and in a supportive organizational culture,
      the highest quality of care and best patient outcomes can be achieved.The purpose
      of this series is to give nurses the knowledge and skills they need to implement
      EBP consistently, one step at a time. Articles will appear every two months to
      allow you time to incorporate information as you work toward implementing EBP at
      your institution. Also, we've scheduled "Ask the Authors" calls every few months
      to provide a direct line to the experts to help you resolve questions. See
      details below.

PMID- 20032670
TI  - Cultivating quality: implementing surgical smoke evacuation in the operating
      room.
AB  - OVERVIEW: Inspired by a presentation at an educational conference, two operating
      room (OR) nurses at Children's Hospital Boston raised concerns at the hospital's
      perioperative evidence-based practice committee meeting about the potential
      hazards associated with exposure to surgical smoke and aerosols. The nurses
      initiated a safety project involving the use of smoke evacuation devices in ORs.
      The subsequent policy development took two years and involved a literature
      review, a survey of other institutions, and the support of numerous stakeholders.
      A utilization review and supportive educational initiatives are ongoing.

PMID- 20032671
TI  - FDA raises safety issues concerning propoxyphene.

PMID- 20032672
TI  - New warnings about immunosuppressive drugs.

PMID- 20032673
TI  - 'The patient will see you now'.

PMID- 20032674
TI  - Building bridges, breaking barriers.

PMID- 20032676
TI  - The dirtiest house in town.

PMID- 20032678
TI  - Dare to change your career course.

PMID- 20032679
TI  - Prepare for a behavioral interview, then ace it!
AB  - By reflecting on your past experiences before an interview, you'll be better
      prepared to respond to an interviewer's questions.

PMID- 20032680
TI  - Growing in your nursing career.
AB  - Deepen your roots and reach new heights in your career while staying with your
      current employer.

PMID- 20032681
TI  - Eight traits make great nursing instructors.
AB  - Now's the perfect time to move into nursing education to teach the next
      generation of nursing students.

PMID- 20032682
TI  - Landing a job in a tough economy.
AB  - If nursing jobs are currently in short supply in your area, use these tips to
      maximize your chances of securing employment.

PMID- 20032683
TI  - Are you ready to move into critical care?
AB  - Discover whether this highly valued specialty is your calling.

PMID- 20032684
TI  - Moving into private geriatric nursing care management.
AB  - Consider starting your own business to help older adults maintain their health
      and functional abilities.

PMID- 20032685
TI  - Do you want to be a staff-development specialist?
AB  - If so, you'll need to stay at the top of your game to teach the latest advances
      to other nurses, healthcare providers, and patients.

PMID- 20032686
TI  - Transitioning from clinician to clinical research coordinator.
AB  - Use your nursing skills and personal qualities to move into this fast-growing,
      intellectually stimulating field.

PMID- 20032690
TI  - The Magnet site visit: your time to shine.
AB  - If you've prepared well, a Magnet site visit can showcase your staff's talents.

PMID- 20032691
TI  - Surviving and thriving on the road.
AB  - A few key steps can help you to make the most of a travel nursing assignment.

PMID- 20032696
TI  - New insights about an old foe.

PMID- 20032697
TI  - Perioperative use of beta-adrenergic antagonists and anemia: known knowns, known
      unknowns, unknown unknowns; and Unknown Knowns.

PMID- 20032699
TI  - Effects of dexmedetomidine and propofol on lower esophageal sphincter and
      gastroesophageal pressure gradient in healthy volunteers.
AB  - BACKGROUND: Many anesthetics reduce lower esophageal sphincter pressure (LESP).
      Reduced pressure and consequent reduction in the gastroesophageal pressure
      gradient (GEPG) thus promotes gastroesophageal reflux and may contribute to
      aspiration pneumonia and associated morbidity. Therefore, the authors compared
      LESP and GEPG during dexmedetomidine and propofol sedation. METHODS: Using a
      randomized, double-blind, crossover design, 11 healthy volunteers were sedated on
      2 separate days. Baseline LESP and GEPG were recorded each day. Subsequently, on
      each day volunteers received three 40-min-long sedative infusions of increasing
      doses of 0.6, 1.2, and 2.4 ng/ml dexmedetomidine or 1, 2, and 4 microg/ml
      propofol. LESP and GEPG were recorded during inhalation and expiration at 20 and
      40 min after starting each infusion phase, and these measurements were averaged.
      Results are presented as mean (95% confidence interval). RESULTS: Two subjects
      did not return for the dexmedetomidine study day, and the dexmedetomidine results
      were unusable in another; propofol results in these volunteers were nonetheless
      retained for analysis. There were no significant differences in LESP and GEPG as
      a function of drug. However, there was a small but significant 7.4 (-1.6 to 
      13.2) mmHg (approximately 25%) dose-dependent decrease in LESP over the range of
      targeted low to high blood levels of each drug. CONCLUSIONS: Both dexmedetomidine
      and propofol have similar effects on LESP and GEPG. Although both of the drugs
      cause some decrease in LESP at high concentrations, it is unlikely that this
      effect would promote gastroesophageal reflux during sedation.

PMID- 20032700
TI  - Acute surgical anemia influences the cardioprotective effects of beta-blockade: a
      single-center, propensity-matched cohort study.
AB  - BACKGROUND: Despite decreasing cardiac events, perioperative beta-blockade also
      increases perioperative stroke and mortality. Major bleeding and/or hypotension
      are independently associated with these outcomes. To investigate the hypothesis
      that beta-blockade limits the cardiac reserve to compensate for acute surgical
      anemia, the authors examined the relationship between cardiac events and acute
      surgical anemia in patients with and without beta-blockade. METHODS: The records
      of all noncardiac, nontransplant surgical patients between March 2005 and June
      2006 were retrospectively retrieved. The primary outcome was a composite that
      comprised myocardial infarction, nonfatal cardiac arrest, and in-hospital
      mortality (major adverse cardiac event). The lowest recorded hemoglobin in the
      first 3 days defined nadir hemoglobin. Propensity scores estimating the
      probability of receiving a perioperative beta-blocker were used to match (1:1)
      patients who did or did not receive beta-blockers postoperatively. The
      relationship between nadir hemoglobin and major adverse cardiac event was then
      assessed. RESULTS: This analysis identified 4,387 patients in whom nadir
      hemoglobin could be calculated; 1,153 (26%) patients were administered beta
      blockers within the first 24 h of surgery. Propensity scores created 827 matched
      pairs that were well balanced for all measured confounders. Major adverse cardiac
      event occurred in 54 (6.5%) beta-blocked patients and in 25 (3.0%) beta-blocker
      naive patients (relative risk 2.38; 95% CI 1.43-3.96; P = 0.0009). The restricted
      cubic spline relationship demonstrated that this difference was restricted to
      those patients in whom the hemoglobin decrease exceeded 35% of the baseline
      value. CONCLUSIONS: beta-Blocked patients do not seem to tolerate surgical anemia
      when compared with patients who are naive to beta-blockers. Prospective studies
      are required to validate these findings.

PMID- 20032702
TI  - Propofol depresses angiotensin II-induced cell proliferation in rat cardiac
      fibroblasts.
AB  - BACKGROUND: Propofol may have beneficial effects on the prevention of angiotensin
      II (Ang II)-induced cardiac fibroblast proliferation via its antioxidative
      properties. The authors hypothesized that propofol may alter Ang II-induced cell
      proliferation and aimed to identify the putative underlying signaling pathways in
      rat cardiac fibroblasts. METHODS: Cultured rat cardiac fibroblasts were
      pretreated with propofol then stimulated with Ang II; cell proliferation and
      endothelin-1 gene expression were examined. The effect of propofol on Ang II
      induced nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive
      oxygen species formation, extracellular signal-regulated kinase phosphorylation,
      and activator protein 1-mediated reporter activity were also examined. The effect
      of propofol on nitric oxide production and protein kinase B and endothelial
      nitric oxide synthase phosphorylations were also tested to elucidate the
      intracellular mechanism of propofol in proliferation. RESULTS: Ang II (100 nm)
      increased cell proliferation and endothelin-1 expression, which were partially
      inhibited by propofol (10 or 30 microm). Propofol also inhibited Ang II-increased
      nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen
      species formation, extracellular signal-regulated kinase phosphorylation, and
      activator protein 1-mediated reporter activity. Propofol was also found to
      increase nitric oxide generation and protein kinase B and nitric oxide synthase
      phosphorylations. Nitric oxide synthase inhibitor (N-nitro-L-arginine
      methylester) and the short interfering RNA transfection for protein kinase B or
      endothelial nitric oxide synthase markedly attenuated the inhibitory effect of
      propofol on Ang II-induced cell proliferation. CONCLUSIONS: The authors' results
      suggest that propofol prevents cardiac fibroblast proliferation by interfering
      with the generation of reactive oxygen species and involves the activation of the
      protein kinase B-endothelial nitric oxide synthase-nitric oxide pathway.

PMID- 20032703
TI  - Bupivacaine inhibits glutamatergic transmission in spinal dorsal horn neurons.
AB  - BACKGROUND: The local anesthetic bupivacaine is thought not only to block sodium
      channels but also to interact with various receptors. Here, the authors focus on
      excitatory glutamatergic transmission in the superficial dorsal horn of the
      spinal cord with respect to its importance for nociceptive processing. METHODS:
      The effects of bupivacaine on the response to exogenous administration of N
      methyl-D-aspartate (NMDA) receptor agonists were examined in lamina II neurons of
      adult rat spinal cord slices using the whole-cell patch-clamp technique. RESULTS:
      Bupivacaine (0.5, 2 mm) dose-dependently reduced the peak amplitudes of exogenous
      NMDA-induced currents. However, this inhibitory effect of bupivacaine (2 mm) was
      not blocked by the presence of tetrodotoxin, a sodium channel blocker, or La(3+),
      a voltage-gated Ca+ channel blocker, and was unaffected by changes in pH
      conditions. Moreover, intrapipette guanosine-5'-O-(2-thiodiphosphate) (1 mm), a G
      protein inhibitor, did not block the reduction of NMDA current amplitudes by
      bupivacaine. Similarly, lidocaine, ropivacaine, and mepivacaine also reduced the
      amplitudes of NMDA-induced currents. CONCLUSIONS: These findings raise the
      possibility that the antinociceptive effect of bupivacaine may be due to direct
      modulation of NMDA receptors in the superficial dorsal horn. In addition to
      voltage-gated sodium channels, glutamate NMDA receptors are also important for
      analgesia induced by local anesthetics.

PMID- 20032707
TI  - Drowning: lifeguard rescue and resuscitation.

PMID- 20032709
TI  - Residual neuromuscular blockade and upper airway muscles.

PMID- 20032711
TI  - Inhibition of muscle acetylcholine receptors by nondepolarizing drugs: humans are
      not unique.

PMID- 20032713
TI  - Ultrasound-guided supraclavicular block: What is intraneural?

PMID- 20032715
TI  - A case of accidental hypotension caused by drug leakage through the rubber piston
      in a prefilled inovan injection 0.3% syringe.

PMID- 20032717
TI  - Preoperative electrocardiograms.

PMID- 20032718
TI  - Optimum lymphadenectomy for esophageal cancer.
AB  - OBJECTIVE: Using Worldwide Esophageal Cancer Collaboration data, we sought to (1)
      characterize the relationship between survival and extent of lymphadenectomy, and
      (2) from this, define optimum lymphadenectomy. SUMMARY BACKGROUND DATA: What
      constitutes optimum lymphadenectomy to maximize survival is controversial because
      of variable goals, analytic methodology, and generalizability of the underpinning
      data. METHODS: A total of 4627 patients who had esophagectomy alone for
      esophageal cancer were identified from the Worldwide Esophageal Cancer
      Collaboration database. Patient-specific risk-adjusted survival was estimated
      using random survival forests. Risk-adjusted 5-year survival was averaged for
      each number of lymph nodes resected and its relation to cancer characteristics
      explored. Optimum number of nodes that should be resected to maximize 5-year
      survival was determined by random forest multivariable regression. RESULTS: For
      pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+)
      cancers, 5-year survival improved with increasing extent of lymphadenectomy. In
      pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum
      lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for
      pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes
      positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for
      pT3/T4. CONCLUSIONS: Greater extent of lymphadenectomy was associated with
      increased survival for all patients with esophageal cancer except at the extremes
      (TisN0M0 and >or=7 regional lymph nodes positive for cancer) and well
      differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T
      classification: resecting 10 nodes for pT1, 20 for pT2, and >or=30 for pT3/T4 is
      recommended.

PMID- 20032719
TI  - Hepatectomy for bilateral primary hepatolithiasis: a cohort study.
AB  - OBJECTIVE: This study aimed to evaluate the perioperative and long-term results
      of partial hepatectomy for patients with complicated bilateral primary
      hepatolithiasis. SUMMARY BACKGROUND DATA: Hepatolithiasis is best managed by a
      multidisciplinary approach. Definitive treatment can be offered using endoscopic,
      percutaneous, laparoscopic, or open surgical approaches. Partial hepatectomy is
      only indicated for recurrent, troublesome, localized, and severe disease
      affecting the liver. METHODS: From January 2000 to December 2006, 136 consecutive
      patients who underwent bilateral (n = 54) or unilateral (n = 82) hepatectomy for
      biliary strictures and bilateral primary hepatolithiasis in our center were
      included in this study. All patients had concomitant bile duct exploration. Their
      perioperative and long-term outcomes were analyzed. RESULTS: The immediate stone
      clearance rates after bilateral and unilateral hepatectomy were 81.5% and 65.9%,
      respectively. Additional postoperative choledochoscopic lithotripsy raised the
      clearance rates to 85.2% and 81.7%, respectively. The hospital mortality rates
      were 5.6% and 0%, respectively, and the complication rates were 46.3% and 46.3%,
      respectively. The 5-year overall survival rates were 98% and 91.5%, respectively.
      CONCLUSION: In selected patients with biliary strictures and bilateral
      hepatolithiasis, partial hepatectomy associated with choledochoscopic lithotripsy
      is a safe and efficacious treatment, with a high immediate stone clearance rate,
      a low long-term stone recurrence rate and good long-term survival.

PMID- 20032720
TI  - Stat 6-dependent induction of myeloid derived suppressor cells after physical
      injury regulates nitric oxide response to endotoxin.
AB  - OBJECTIVE: To delineate the role of T-helper 2 (Th2) cytokines in the induction
      of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric
      oxide production. BACKGROUND: Trauma induces myeloid cells that express
      CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This
      article explores the mechanisms that induce TIMSC and the effects on nitric oxide
      production in response to endotoxin. METHODS: TIMSC were studied in response to
      Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines
      was studied in STAT6-/- mice. Accumulation of TIMSC in spleens was studied using
      flow cytometry and immunhistochemistry. Plasma was recovered to measure
      accumulation of nitric oxide metabolites. RESULTS: TIMSC accumulated in the
      spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with
      large inductions of arginase activity. Significant blunting in both the
      accumulation of TIMSC in the spleen and induction of arginase 1 was observed in
      STAT6-/- mice after physical injury. Accumulation of nitric oxide metabolites to
      endotoxin was observed in STAT6-/- mice. CONCLUSION: This study shows that
      induction of CD11b+/Gr1+ cells after physical injury play an essential role in
      the regulation of nitric oxide production after a septic challenge. The
      accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To
      our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel
      finding. This observation adds to the possibility that TIMSC could play an
      important role in immunosuppression observed after physical injury.

PMID- 20032721
TI  - The effects of stress and coping on surgical performance during simulations.
AB  - OBJECTIVE: This study investigates the effects of surgeons' stress levels and
      coping strategies on surgical performance during simulated operations. METHODS:
      Thirty surgeons carried out each a non-crisis and a crisis scenario of a
      simulated operation. Surgeons' stress levels were assessed by several measures:
      self-assessments and observer ratings of stress, heart rate, heart rate
      variability, and salivary cortisol. Coping strategies were explored qualitatively
      and quantified to a coping score. Experience in surgery was included as an
      additional predictor. Outcome measures consisted of technical surgical skills
      using Objective Structured Assessment of Technical Skill (OSATS), nontechnical
      surgical skills using Observational Teamwork Assessment for Surgery (OTAS), and
      the quality of the operative end product using End Product Assessment (EPA). Uni-
      and multivariate linear regression were used to assess the independent effects of
      predictor variables on each performance measure. RESULTS: During the non-crisis
      simulation, a high coping score and experience significantly enhanced EPA (beta1,
      0.279; 0.009-0.460; P= 0.04; beta2, 0.571; 4.328-12.669, P< 0.001; respectively).
      During the crisis simulation, a significant beneficial effect of the interaction
      of high experience and low stress on all performance measures was found (EPA:
      beta, 0.537; 2.079-8.543; OSATS: beta, 0.707; 8.708-17.860; OTAS: beta, 0.654;
      13.090-30.483; P< 0.01). Coping significantly enhanced nontechnical skills (beta,
      0.302; 0.117-1.624, P= 0.03). CONCLUSIONS: Clinicians' stress and coping
      influenced surgical performance during simulated operations. Hence, these are
      critical factors for the quality of health care.

PMID- 20032724
TI  - Halving our sorrows and doubling our joys.
AB  - Late yesterday, I received a terrible shock. I e-mailed a colleague in another
      one of our agency's offices, about 60 miles from the office where I work, asking
      her to review an educational plan I was developing for our agency's Outcome and
      Assessment Information Set-C follow-up training. She responded she didn't have
      time to do the review for at least several days because she was feeling
      overwhelmed, not only with work responsibilities, but because, as I may I have
      heard, "We lost Cathy Smith (not her real name) last night."

PMID- 20032725
TI  - Medication use among older adults in a home care setting.

PMID- 20032727
TI  - A multidisciplinary approach to the care of the ventilator-dependent child at
      home: a case study.
AB  - An estimated 4,300 children in the United States are managed at home on
      mechanical ventilation. Despite frequent overwhelming challenges, most families
      are able to maintain a safe and enriching life for the child if they are
      supported in the home by a multidisciplinary professional team. The Pennsylvania
      Ventilator Assisted Children's Home Program (VACHP) is a statewide program that
      coordinates the care of children at home on mechanical ventilation and advocates
      for the support of families in the community. In this case study, VACHP
      illustrates the importance of a multidisciplinary approach to care in order to
      ensure a safe and successful home management of children on mechanical
      ventilation.

PMID- 20032729
TI  - OASIS inter-rater reliability and reimbursement: a study of inter-rater
      reliability of the Outcome and Assessment Information Set (OASIS): its effects on
      the Home Health Resource Group (HHRG) and reimbursement.
AB  - One of the outcomes of the initial Outcome and Assessment Information Set (OASIS)
      is to establish a level of reimbursement through the Medicare Prospective Payment
      System (PPS). Several inter-rater reliability (IRR) studies have noted
      differences in responses to individual questions within the OASIS but little is
      known about how variations in scoring might affect the final reimbursement
      projection. In a one-way repeated measures design study, the OASIS was completed
      on 52 patients by both an RN and a PT within a 24-hour timeframe and the
      projected reimbursement rates were compared. Fifty-four percent of the outcomes
      of the assessment pairs were identical; differences in the remaining 46% were
      equally divided between RNs and PTs in projecting a higher reimbursement rate and
      with similar distributions. The mean difference in projected reimbursement rates
      was $16.43 per episode with no significant difference between the PT and RN Home
      Health Resource Group (HHRG) distributions.

PMID- 20032730
TI  - Introducing music therapy in hospice and palliative care: an overview of one
      hospice's experience.
AB  - A middle-aged man with lung cancer breathes more easily and reduces his need for
      pain medication after participating in music-focused relaxation. An 8-year-old
      boy with cancer writes songs and records a CD for his family. An elderly woman in
      the final stages of Alzheimer's who is no longer able to speak sings a few words
      of her favorite lullaby to her adult daughter. A much-loved grandmother dies
      peacefully as her family sings her favorite spiritual songs to the accompaniment
      of a music therapist's folk harp. These illustrations demonstrate the role that
      music therapy plays in attending to the physical, emotional, and spiritual needs
      of hospice and palliative care patients and families while respecting their
      dignity and celebrating their lives.

PMID- 20032731
TI  - Online resources for pediatric home care clinicians.
AB  - Pediatric home care clinicians dealing with premature infants can encounter any
      number of unusual conditions related to their patient's prematurity. Finding
      reliable information on the condition can be difficult for a clinician who does
      not have immediate access to a health sciences library. There are, however, many
      useful, reliable websites that can be consulted with a laptop that has wireless
      access. This article reviews a variety of useful websites with a wealth of
      evidence-based information. The author also provides information on Health on the
      Net (HON), a nongovernmental, nonprofit organization that has established a code
      of conduct that websites must meet in order to display their seal.

PMID- 20032732
TI  - Experiencing the benefits of nonprofit home healthcare and hospice employment.

PMID- 20032733
TI  - A home away from home: a unique hospice model.

PMID- 20032734
TI  - Anterior shoulder forces in professional and Little League pitchers.
AB  - BACKGROUND: The developing musculoskeletal system of a youth pitcher is
      substantially different from that of the adult professional pitcher, predisposing
      the younger players to a different set of injuries. METHODS: High-speed
      videography of 39 professional and 13 youth pitchers were obtained. High-speed
      motion analysis was performed to calculate average anterior forces and arm
      positions at maximal force generation. RESULTS: Professional players generated an
      average of 33.8+/-14.4 N/kg maximal anterior force, corresponding to 151.9+/-17.0
      degrees of external rotation. Youth pitchers generated 16.2+/-3.8 N/kg of
      anterior forces, corresponding to 118.0+/-23.4 degrees of external rotation. The
      degree of coronal abduction and horizontal abduction between the 2 groups were
      not significantly different-92.4+/-9.0 degrees in professionals versus 91.7+/-7.9
      degrees in the youth and 11.1+/-11.1 degrees of horizontal abduction in
      professionals versus 7.8+/-14.1 degrees in the younger throwers. Professional
      pitchers exerted higher internal rotation torque at 19.4+/-4.1 Nm/kg versus 5.6+/
      1.0 Nm/kg in youth, and compressive forces were found to be 121.7+/-21.7 N/kg in
      professional pitchers compared with 47.5+/-7.6 N/kg in the youth pitchers.
      CONCLUSIONS: Youth pitchers experience significant anterior shoulder forces and
      internal rotation torques, although these are lower than professional pitchers.
      CLINICAL RELEVANCE: Overhead throwing as a youth can lead to shoulder injuries
      and can predispose the shoulder to more significant injuries as an adult pitcher.

PMID- 20032735
TI  - Arthroscopic management of osteochondritis dissecans of the capitellum: mid-term
      results in adolescent athletes.
AB  - BACKGROUND: The optimal treatment of osteochondritis dissecans (OCD) of the
      capitellum in adolescent athletes remains challenging. The purpose of this study
      was to investigate the mid-term results of arthroscopic treatment of OCD of the
      capitellum in a series of adolescents. METHODS: We identified 25 consecutive
      patients at our institution that underwent arthroscopic treatment for OCD of the
      capitellum since 1999. Ten elbows were treated by arthroscopic debridement and
      drilling alone, whereas 12 elbows required additional mini-arthrotomies for bone
      grafting or the removal of large loose bodies after arthroscopy. The clinical
      charts and operative reports of these patients were retrospectively reviewed for
      relevant clinical information including age, sport, character of symptoms,
      preoperative and postoperative range of motion, return to sport, and
      postoperative complications. Twenty-one patients (22 elbows) were reached to
      determine their current elbow function and athletic activity using the Single
      Assessment Numerical Evaluation score. RESULTS: The average age of the patients
      in our series was 13.1 years. All patients participated in organized athletics
      that involved the upper extremity and had undergone an average of 10.2 months of
      nonoperative treatment before surgery. At a mean follow-up of 48 months, the
      patients gained an average of 17 degrees of extension and 10 degrees of flexion
      after surgery. Both the improvement in flexion and extension were statistically
      significant compared with the preoperative range of motions (P=0.001, P=0.01).
      When patients were asked to rate their elbow function from 0% to 100% using the
      Single Assessment Numerical Evaluation score, the average rating was 87%.
      Eighteen of 21 patients (86%) returned to participate in their sport at their
      preinjury level. CONCLUSION: Arthroscopic management of capitellar OCD in
      adolescent athletes results in significantly improved range of motion and a high
      rate of return to athletics. Accompanying arthrotomy may be required for large
      loose body removal or bone grafting.

PMID- 20032736
TI  - Fixation of juvenile osteochondritis dissecans lesions of the knee using poly
      96L/4D-lactide copolymer bioabsorbable implants.
AB  - BACKGROUND: The fixation of juvenile osteochondritis dissecans (OCD) lesions has
      been described using metal implants, staples, bone pegs, and bioabsorbable
      implants. Bioabsorbable fixation has potential benefits including not requiring a
      second surgery for implant removal, no interference on postoperative magnetic
      resonance imaging (MRI) scans, and a potentially lower incidence of prominent
      hardware. The possible complications of bioabsorbable fixation include synovitis,
      loss of fixation owing to noncompressive properties, and sterile abscess
      formation. The results of bioabsorbable fixation of juvenile OCD lesions of the
      knee have not been well studied. The purpose of this study was to evaluate the
      efficacy and safety of a bioabsorbable copolymer fixation in the management of
      unstable OCD lesions of the knee in adolescents. METHODS: This is a retrospective
      case series of patients with unstable OCD lesions of the knee that were treated
      with poly 96L/4D-lactide copolymer bioabsorable implants. Information was
      gathered through 3 standardized and validated knee-function questionnaires,
      participants' medical records, plain films, MRIs, and pain level and satisfaction
      scale questionnaires. RESULTS: Twenty-four knees in 24 patients were evaluated.
      The mean age at the time of surgery was 14.4 years. The mean follow-up was 39.6
      months. The mean International Knee Documentation Committee score at follow-up
      was 84.9, the mean Lysholm score was 88.0, and the mean Tegner score was 7.9.
      Plain films at an average of 19.2 months postoperatively revealed interval
      healing in 9 patients, no significant change in 1 patient, complete healing in 13
      patients, and loose bodies with no interval healing in 1 patient. MRIs were
      obtained postoperatively in 17 knees, with a mean follow-up of 22.4 months.
      Interval healing was present in 16 of 17 MRIs, consistent with the plain film
      findings. Twenty-two of 24 patients had good-to-excellent outcomes. CONCLUSION:
      Poly 96L/4D-lactide copolymer bioabsorable implants seem to be safe and effective
      for the management of unstable juvenile OCD lesions of the knee. They offer
      stability for the healing OCD lesions, with minimal reaction from degradation
      products.

PMID- 20032737
TI  - Effect of intra-articular pressurization associated with arthroscopy on the
      immature physis: investigation in an animal model.
AB  - BACKGROUND: Despite the increased use of arthroscopy in pediatric orthopaedics,
      there is a paucity of data regarding the potential long-term effects of this
      procedure on the immature physis. The purpose of this study was to test the
      hypothesis that elevated intra-articular pressures used during arthroscopic
      surgery do not result in growth disturbances or morphologic alterations in the
      epiphyseal plate. METHODS: Twenty-seven 6-week-old skeletally immature New
      Zealand white rabbits were divided into experimental (n=21) and control groups
      (n=6). In the experimental group, a hydraulic pump was used to pressurize 1
      randomly assigned knee joint per rabbit to intra-articular pressures of 120 mm Hg
      for 2 hours. In the control group, rabbits received a sham intervention. All
      rabbits were killed at 6 months of age (skeletal maturity), and their tissues
      were evaluated grossly, radiographically, and histologically. Data collection
      included gross measurements (femur and tibia lengths, evaluation of varus/valgus
      angulation, and knee joint range of motion) and histologic analyses to determine
      whether morphologic changes were present in the articular cartilage or physis.
      Confidence intervals were used to test for statistical equivalence. RESULTS: The
      pressurized and control groups had statistically equivalent gross measurements.
      No significant articular cartilage or physeal lesions were identified in
      histologic sections or radiographic studies. CONCLUSION: This study provided no
      evidence that arthroscopic pressurization of the knee joint to 120 mm Hg for 2
      hours significantly affected physeal growth in a skeletally immature rabbit
      model. CLINICAL RELEVANCE: This study provides the first direct evidence that
      arthroscopic pressurization of immature joints has no clinically significant
      adverse long-term effects. Therefore, novel uses of arthroscopy in pediatric
      patients should be explored without undue concern with regard to premature
      physeal closure.

PMID- 20032738
TI  - Acetabular cartilage and labral damage observed during surgical hip dislocation
      for stable slipped capital femoral epiphysis.
AB  - BACKGROUND: Surgical hip dislocation allows the surgeon full visualization of the
      proximal femur and acetabulum. It also makes it possible to directly observe the
      pathologic relationship between the proximal femur and acetabular rim with hip
      motion. The purpose of this study is to classify acetabular cartilage and labral
      damage that is present at the time of surgical hip dislocation for the treatment
      of symptomatic stable slipped capital femoral epiphysis (SCFE) hips. METHODS: A
      retrospective study was performed at 2 North American centers on patients with a
      stable SCFE who had a surgical hip dislocation for chronic symptoms. The severity
      of SCFE (slip angle) was measured as mild (0-30 degrees), moderate (30-60
      degrees), and severe (60-90 degrees). The degree of acetabular and labral damage
      was classified in each patient according to the Beck classification used for
      femoroacetabular impingement. RESULTS: Thirty-nine hips in 36 patients that
      underwent open surgical dislocation for diagnosis of stable SCFE were included.
      The breakdown of the radiographic severity of the SCFE was 8 mild, 20 moderate,
      and 11 severe. Labral injury was observed in 34 of 39 hips. Using the Beck
      classification for labral injury, there were 21 type 1 injuries, 9 type 2
      injuries, and 4 type 3 injuries. Cartilage injury was present in 33 of 39 hips.
      Using Beck classification for cartilage damage, there were 6 grade 0, 5 grade 1,
      10 grade 2, 4 grade 3, 10 grade 4, and 4 grade 5 injuries. The average depth of
      cartilage damage was 5 mm (range, 2-10 mm). CONCLUSIONS: In this study,
      significant chondromalacia and labral injury was observed in hips afflicted with
      SCFE. Surgical hip dislocation allowed direct confirmation of the impingement of
      the prominent metaphysis on the acetabular labrum and cartilage.

PMID- 20032739
TI  - Outcome of in situ pinning in patients with unstable slipped capital femoral
      epiphysis: assessment of risk factors associated with avascular necrosis.
AB  - INTRODUCTION: Avascular necrosis (AVN) is a devastating complication following
      treatment of unstable slipped capital femoral epiphysis (SCFE). The advent of
      newer methods such as open reduction and surgical dislocation of the hip has
      increased the debate on the optimal method of treatment. However, the risk or
      predisposing factors for AVN remain unclear. We aimed to assess the outcome of in
      situ fixation and the risk factors associated with AVN. METHODS: We
      retrospectively reviewed the records of 27 patients (27 hips) with unstable SCFE
      out of the 280 children managed for SCFE from 1995 to 2006. The mean age in years
      of the patients at surgery was 12.2+/-1.58, and our sample comprised 70.4% males,
      and 29.6% females, with a mean follow-up of 3.1+/-1.9 years. Univariable and
      multivariable binomial regression models were used to assess factors predisposing
      to AVN. RESULTS: AVN occurred in 22.2% (6/27) of the children with unstable SCFE.
      After adjustment for age, race, and time to surgery, sex and preoperative slip
      angle were the only 2 significant factors related to an increased risk of AVN,
      risk ratio (RR)=4.15, 95% confidence interval=1.00-17.19, P=0.05 and RR=1.04, 95%
      confidence interval=1.00-1.07, P=0.03, respectively. Female children constitute a
      high-risk group for AVN in this subgroup. CONCLUSIONS: AVN is still prevalent
      among patients with unstable SCFE who underwent in situ pinning. Female sex and
      slip magnitude are potential predisposing factors for developing AVN.

PMID- 20032740
TI  - Magnetic resonance evaluation of acetabular residual dysplasia in developmental
      dysplasia of the hip: a preliminary study of 27 patients.
AB  - Thirty-one hips in 27 young girls, treated for developmental dysplasia of the hip
      in the authors' institute since 2003, showed persistent radiographic evidence of
      residual acetabular dysplasia. These hips were registered as candidates for
      pelvic osteotomy. A prospective study was conducted and these hips were evaluated
      by magnetic resonance imaging (MRI); the average age of the patients was 5 years.
      MRI measurement of acetabular angle and acetabular head index in 2 different
      landmarks (bone and cartilage) was performed. The results were correlated with
      plain radiographic film evolution. MRI studies revealed sufficient cartilaginous
      acetabular coverage in 27 hips, cartilaginous acetabular dysplasia in 2 hips, and
      short acetabulum in 2 others. The 27 hips with thick cartilage of the acetabular
      roof were subsequently followed up by plain radiographs. The average follow-up
      period was 2.1 years. The authors observed a spontaneous progressive ossification
      of the cartilaginous acetabular roof in all the 27 cases. In 4 cases, the
      correction of the acetabular angle was complete. They concluded that MRI promotes
      more accurate selection of patients for pelvic osteotomy and aids in the choice
      of the most appropriate type of osteotomy. Clinical imaging examples are
      presented and need to be further evaluated.

PMID- 20032741
TI  - The evaluation of hip muscles in patients treated with one-stage combined
      procedure for unilateral developmental dysplasia of the hip: part II: isokinetic
      muscle strength evaluation.
AB  - BACKGROUND: To assess the isokinetic muscle strength (IMS) of hip flexor and
      extensor muscles in patients treated with one-stage combined procedure for
      developmental dysplasia of the hip and analyze the effect of the status of hip
      muscles on IMS. METHODS: Twenty-two patients were included in the study. The mean
      age was 154.4+/-34.6 (110-216) months and the mean follow-up was 112.6+/-32.0 (68
      159) months. All patients underwent complete tenotomy of the iliopsoas muscle to
      ease open reduction and had excellent results according to the modified McKay
      criteria of Barrett and type I hips according to the radiologic criteria of
      Severin. All patients had earlier magnetic resonance imaging examination that
      revealed reattachment of the iliopsoas in 7 (32%) patients. IMS measurements were
      performed at 120 degrees/s and 240 degrees/s. The peak torque (PT), PT angle,
      total work (TW), and average power (AP) values of operated and nonoperated hips
      were recorded separately for flexors and extensors. RESULTS: For flexors, TW and
      AP values were lower at the operated hip when compared with the nonoperated hip
      at both angular velocities. PT was only lower at the operated hip at 120
      degrees/s. For extensor muscles, PT, TW, AP, and PT angle showed no statistically
      significant difference at either angular velocity. For flexors, the PT deficit
      between the operated and nonoperated hips at 120 degrees/s and 240 degrees/s was
      measured as 15.3% and 8.0%, respectively. There was no difference between the
      flexor muscles of operated and nonoperated hips considering PT, TW, and AP at
      both angular velocities in patients with reattachment. The IMS deficit of flexor
      muscles at 120 degrees/s was significantly higher in patients without
      reattachment of iliopsoas when compared with those with reattachment, and
      correlated to the widths of the iliopsoas muscle at levels II and III.
      CONCLUSIONS: Assessing the results of surgical treatment of DDH with conventional
      radiologic and functional criteria might be misleading in some patients with
      excellent results because some of these patients, particularly those without
      reattachment of the iliopsoas muscle, experience significant weakness in hip
      flexion.

PMID- 20032742
TI  - Risk factors for vascular repair and compartment syndrome in the pulseless
      supracondylar humerus fracture in children.
AB  - BACKGROUND: The aims of this study were to determine how often fracture reduction
      alone restored pulses and vascular perfusion in displaced supracondylar humerus
      fractures with absent distal pulses on presentation, and whether any preoperative
      factors were associated with the need for vascular repair and vascular
      complications. METHODS: We reviewed 1255 supracondylar humerus fractures in
      children treated operatively over 12 years at one institution. We identified 33
      patients who presented with displaced supracondylar humerus fractures and absent
      distal pulses. We reviewed the management and outcome of these injuries. RESULTS:
      Thirty-three (of 1255) patients presented with a pulseless supracondylar humerus
      fracture (2.6%). The patients were divided into 2 groups: those at presentation
      whose hand was well perfused (n=24) or poorly perfused (9). None (0 of 24) of the
      well-perfused patients underwent vascular repair; 3 had open reduction. Of the 21
      well-perfused patients undergoing closed reduction and pinning, 11 (of 21) had a
      palpable pulse after surgery and 10 (of 21) remained pulseless but well perfused;
      all did well clinically. Of the 9 patients in the poorly perfused group, 4
      underwent vascular repair, and compartment syndrome developed in 2 during the
      postoperative period. In just over half of patients with a poorly perfused hand
      (5 of 9), fracture reduction alone was the definitive treatment. CONCLUSIONS: In
      the largest series of children with pulseless displaced supracondylar humerus
      fractures in the literature, we identify 2 distinct populations, with the
      perfusion status of the hand at time of presentation correlating significantly
      with the ultimate need for vascular repair. In patients presenting with a well
      perfused hand, fracture reduction alone was sufficient treatment in all 24 (of
      24) cases, and no patients developed compartment syndrome. Nearly half of these
      patients still had an absent palpable pulse but well-perfused hand after closed
      reduction, yet did well clinically. Patients presenting with a poorly perfused
      hand are at high risk for vascular repair and compartment syndrome.

PMID- 20032743
TI  - Delayed presentation of a brachial artery pseudoaneurysm after a supracondylar
      humerus fracture in a 6-year-old boy: a case report.
AB  - Supracondylar fractures of the humerus are the most common elbow fractures in
      children, accounting for 60% to 70% of all pediatric elbow fractures. These
      fractures often have neurovascular complications because of deformity and the
      sharp nature of the fracture fragments. The management of patients who present
      with diminished or absent pulses, but a well-perfused extremity is a topic of
      debate. Between 3% and 14% of patients present with an altered vascular
      examination and a consistent treatment logarithm has not been proposed in the
      literature. To our knowledge, a brachial artery pseudoaneurysm presenting in a
      delayed fashion in the setting of a normal vascular examination has not been
      reported. We report a 6-year-old boy who had a delayed presentation of a brachial
      artery pseudoaneurysm after a supracondylar humerus fracture, which was repaired
      with a saphenous vein graft. This is to emphasize close neurological and vascular
      monitoring even in the setting of a well-perfused hand. In addition, this would
      suggest that closer postoperative evaluation in significantly displaced fractures
      should be performed, even beyond the fracture healing stage.

PMID- 20032744
TI  - Ossification of the proximal humerus in children with residual brachial plexus
      birth palsy: a magnetic resonance imaging study.
AB  - BACKGROUND: Children with residual brachial plexus birth palsy may develop
      deformities of the humeral head and the glenoid. Surgical treatment has been
      described to maximize function and to lessen deformity by means of glenohumeral
      remodeling. The timing and technique of surgical intervention have not been
      resolved. The timing of the appearance on magnetic resonance imaging of the
      ossific nuclei in patients with brachial plexus birth palsy has not been
      described. We examined the timing of ossification about the proximal humerus. Our
      hypothesis was that the timing of ossification of the proximal humerus differs
      between the side involved in brachial plexus palsy and the uninvolved side.
      METHODS: A retrospective study was performed of 117 children with residual
      brachial plexus birth palsy (aged 5 mo to 10 y) who had magnetic resonance
      imaging scans of the bilateral shoulders performed at our institution between
      2000 and 2007. All axial slices were reviewed by a single observer for evidence
      of ossification of the humeral head epiphysis, the greater tuberosity, and the
      lesser tuberosity, as well as for evidence that the 3 were coalesced. Statistical
      analysis was performed to compare the involved and uninvolved sides. RESULTS: The
      appearance of the greater tuberosity ossific nucleus on the involved side was
      significantly delayed. There was a trend towards delay in the appearance of the
      lesser tuberosity ossific nucleus and the coalescence of the 3 ossific nuclei on
      the involved side. The duration during which ossification of the involved
      brachial plexus side occurred was generally shorter compared with the uninvolved
      side. CONCLUSION: There is delay in the ossification of the involved side in
      brachial plexus birth palsy, and a shorter duration of ossification.

PMID- 20032745
TI  - Long-term results of lateral band translocation for the correction of swan neck
      deformity in cerebral palsy.
AB  - PURPOSE: The aim of this study was to evaluate the long-term effect of lateral
      band translocation for correcting swan neck deformity in patients with cerebral
      palsy at a minimum follow-up of 5 years. METHODS: Swan neck deformities of 62
      fingers were corrected using a modified lateral band translocation. At 1-year and
      5-year follow-up, any recurrence of hyperextension was recorded through
      nonconstrained evaluation. Active extension of the proximal interphalangeal joint
      beyond 0 degree was considered a recurrence. RESULTS: Correction was successful
      for 84% of the operated fingers at 1-year follow-up. After 5 years, the success
      rate had decreased to 60%. Furthermore, no relationship was found between any of
      the concomitant surgical procedures and the number of patients with recurrences.
      CONCLUSIONS: The long-term result of lateral band translocation is disappointing
      in our series, and it should not be advocated as a procedure with long-lasting
      success in patients with cerebral palsy.

PMID- 20032746
TI  - Validity and reliability of physical functioning computer-adaptive tests for
      children with cerebral palsy.
AB  - BACKGROUND: The purpose of this study was to assess the concurrent validity and
      reliability of scores from 4 new parent-report computer-adapted testing (CAT)
      programs developed to measure the physical functioning of children with cerebral
      palsy (CP). The Shriners Hospitals for Children CP-CAT battery includes upper
      extremity skills, lower-extremity and mobility skills, activity, and global
      physical health. METHODS: This was a prospective study of 91 children with CP who
      were tested cross-sectionally and 27 children with CP who were administered the
      CP-CAT programs twice within approximately a 1-month interval. We examined the
      concurrent validity of the 4 Shriners Hospitals for Children CP-CAT programs by
      Pearson correlations with comparative parent-report instruments. The scale
      reliability was tested by developing estimates of marginal reliability; test
      retest reliability was assessed by intraclass correlations. RESULTS: Pearson
      correlations were moderate to high in matching content domains of the CATs with
      the comparison measures. Marginal reliability estimates were always better for
      the CAT program than the comparative instruments. Average test-retest reliability
      using Intraclass correlations across the 4 CATs was ICC3,1=0.91 with a range of
      0.88 to 0.94. CONCLUSIONS: We found the CAT scores to be related to expected
      domains from external instruments, to have good scale reliability, and to have
      stable scores as determined by test-retest reliability. These results support the
      use of parent-report CATs in the assessment of physical functioning in children
      with CP.

PMID- 20032747
TI  - Complications of intrathecal baclofen pump therapy in pediatric patients.
AB  - BACKGROUND: The aim of this study was to investigate and evaluate complications
      of intrathecal baclofen (ITB) pump implantation and maintenance in children with
      cerebral palsy. METHODS: We reviewed our entire consecutive series of pediatric
      patients treated with ITB between 1997 and 2006 at our hospital. There were 174
      patients with a diagnosis of cerebral palsy, 8 with mixed dystonia, 2 with
      athetosis, and 3 with pure dystonia. During follow-up, 8 deaths occurred with no
      evidence of pump or catheter malfunction in any way contributing to the cause of
      death. Acute infection within 60 days of the surgery and late infection rates
      were calculated on the basis of number of incidents and incidents/follow-up
      patient years, respectively. Independently, a blinded caregiver phone
      questionnaire was completed in 92 cases. RESULTS: There were 316 surgical
      procedures; 161 were initial ITB pump implants at our institution. The average
      age at initial implant was 12 years, with an average follow-up of 3 years, 2
      months. There were 80 planned replacement procedures (46 battery expirations and
      3 planned pump replacements during posterior spinal fusion, 26 catheter
      replacements for posterior spinal fusion, and 5 reinsertions). There were 78
      procedures in 57 patients related to complications, and the acute infection rate
      was 4.0%. The probability of developing a late infection was 1.0% per year of
      follow-up. On the basis of the follow-up questionnaire, 81% of parents/caregivers
      were satisfied with the treatment, and 87% would recommend ITB therapy.
      CONCLUSIONS: ITB therapy is a safe and effective treatment for severe spasticity
      in the pediatric population, but does have a 31% rate of complications requiring
      surgical management over a 3-year treatment period. Parents and caregivers have a
      high rate of satisfaction and most would recommend the treatment to others.

PMID- 20032748
TI  - Plantar pressures following Ponseti and French physiotherapy methods for
      clubfoot.
AB  - BACKGROUND: Recent trends have led to interest in nonoperative treatments for
      clubfoot (Ponseti casting and French Physiotherapy). Current studies show good
      sagittal kinematic motion after both treatments in the young child, but changes
      in plantar loading after these treatments have not yet been reported. METHODS:
      Pedobarograph data were collected with the Emed System on 151 clubfeet, treated
      with either Cast (79 feet) or physiotherapy (PT, 72 feet), at the age of 2 years.
      Medial and lateral differences in plantar pressures, contact area, and contact
      time, were assessed in the hindfoot, midfoot, and forefoot. An assessment of
      forefoot adductus was made, while the center of the pressure line was tracked
      both medially and laterally. Seventeen controls were used for comparison.
      RESULTS: When comparing Cast feet with PT feet, most differences in plantar
      pressures were found in the hindfoot and medial midfoot. Peak pressure, maximum
      force, and pressure time integral were all found to be decreased in the medial
      hindfoot after PT compared with casting. Maximum force was also less in the
      lateral hindfoot and peak pressure was less in the medial midfoot for the PT feet
      compared with the Cast feet. When compared with controls, both Cast and PT feet
      had increased pressure, force, contact time, contact area, and pressure time
      integral in the lateral midfoot, whereas the same measures were all significantly
      decreased in the first metatarsal region. Forefoot adductus was present in both
      groups compared with controls. The center of the pressure line was significantly
      displaced to the lateral side of the foot in both groups; however, when assessing
      medial displacement, only the PT feet had significantly less medial distribution
      compared with control feet. CONCLUSION: Pedobarography illustrates residual
      pressure differences during gait in children with nonoperatively treated
      clubfeet. These data provide a more detailed description of dynamic foot loading
      and residual deformity than sagittal plane kinematics alone.

PMID- 20032749
TI  - The treatment of vertebral and chest wall deformities with expandable
      thoracoplasty and a prosthetic expandable implant.
AB  - BACKGROUND: Expansion thoracoplasty is a temporary solution to allow complete
      pulomonary development in the setting of vertebral and rib cage deformities.
      After thoracoplasty, an expandable implant is needed to maintain the correction.
      The Growing Spine Profiler (GSP) is a new type of readjustable rib distracter.
      The purpose of this study was to evaluate the experiences of surgeons in Europe
      with the implantation of the GSP. METHODS: We retrospectively reviewed 44
      patients that underwent placement of the GSP at 15 sites throughout Europe. The
      mean age at the time of surgery was 6.24 years. Basic demographic data and
      postoperative management were reviewed. All patients received an opening-wedge
      thoracostomy with device implantation and expansion thoracoplasty.
      Retrospectively, the original indications for implantation were determined.
      Digital images of the radiographs were used to measure coronal and sagittal
      parameters. RESULTS: The most common diagnoses for implantation were
      hemivertebrae (9), hemivertebrae with chest wall deformity (10), and unilateral
      bar (8). Outcomes were available for 43 patients with a mean follow-up period of
      3.07 years. There were 23 patients that had an adverse event. Rib fractures were
      the most common adverse event, with 8 incidents in 7 patients. Radiographically,
      coronal curve magnitudes were maintained, whereas sagittal kyphosis gradually
      increased. CONCLUSIONS: The GSP was effective in the maintenance of deformity,
      while providing a moderate complication rate. Further studies need to be
      performed to determine the safety and efficacy of this implant.

PMID- 20032750
TI  - Letter to the editor on "Quantitative evaluation of angular measurements on plain
      radiographs in patients with slipped capital femoral epiphysis".

PMID- 20032752
TI  - Should social media be used to communicate with patients?

PMID- 20032753
TI  - Maternal experience with neonatal jaundice.
AB  - PURPOSE: To describe the lived experience of mothers having an infant with
      neonatal jaundice. STUDY DESIGN AND METHODS: A descriptive phenomenological
      design with 6 mothers who had infants with neonatal jaundice. Streubert's method
      of phenomenology guided the collection, organization, and analysis of data to
      abstract themes. RESULTS: Eight major themes emerged relating to the lived
      experience: (1) physical and emotional exhaustion, (2) feeling robbed, (3)
      distressed by infant's physical appearance, (4) loss of control, (5) maternal
      vigilance, (6) feeling discounted but only for so long, (7) family impact, and
      (8) supportive environment. Three major themes emerged relating to the mother's
      educational experience: (1) everyone has a different opinion, and therefore no
      one really knows for sure; (2) feeling defensive and at fault; and (3) knowing
      now what I would do differently if I had another baby. Mothers reported receiving
      infant care advice contrary to guidelines from multiple healthcare providers.
      CLINICAL IMPLICATIONS: In this study the physical, emotional, and learning needs
      of the mothers were rarely met. Nurses are the healthcare professionals who have
      the most contact with new mothers, and therefore must remain current with the
      evidence for appropriate care. Much needs to be done to help mothers who have
      infants with neonatal jaundice. Additional studies about how nurses and other
      healthcare providers interact with families facing this problem are warranted.

PMID- 20032755
TI  - Caring for the pregnant woman with neurofibromatosis.
AB  - Neurofibromatosis (NF) is one of the most common inherited single-gene disorders
      in humans, and is expressed as two distinct types: Type I (von Recklinghausen
      disease) and Type II, which occurs much less frequently. When it was first
      reported in the obstetric literature in 1906 by Brickner, neurofibromatosis was
      called "fibroma moluscum contagiosum." This article presents a case of a 20-year
      old woman with NF Type I who became pregnant. The clinical challenges of NF and
      pregnancy are explored through the collaborative relationships between the
      patient and two clinical nurse specialists from obstetric and neuroscience
      nursing. The case study provides valuable information for nurses who want to
      provide evidence-based care.

PMID- 20032757
TI  - If transmen can have babies, how will perinatal nursing adapt?
AB  - Reproductive technology has made it possible for those born biologically female
      and who have partially transitioned to the male gender via hormones to become
      pregnant and give birth. This article explores the role of the perinatal nurse in
      providing care during the obstetric experience for a transgender male and his
      significant other. A carefully executed plan of care can assist the nurse in
      providing nonjudgmental, nondiscriminatory physical and emotional nursing care,
      and ensure that the family's healthcare needs are met and that their transition
      into parenthood is effective.

PMID- 20032758
TI  - Postpartum follow-up: can psychosocial support reduce newborn readmissions?
AB  - PURPOSE: To determine whether there was a relationship between postpartum
      psychosocial support from healthcare providers and the rate of normal newborn
      readmissions (NNRs), and whether there was a cost benefit to justify an
      intervention. STUDY DESIGN AND METHODS: Data were abstracted for all normal
      newborn births from 1999 to 2006 (N = 14,786) at a community hospital in southern
      California at three different time periods: (1) at baseline prior to any
      intervention (1999-2000), (2) the 4 years during the comprehensive psychosocial
      support intervention (2001-2004), and (3) the 2 years during a limited
      psychosocial support intervention (2004-2006). A cost-benefit analysis was
      performed to analyze whether the financial benefits from the intervention matched
      or exceeded the costs for NNRs. RESULTS: There was a significantly lower
      readmission rate of 1.0% (p = < .001) during the comprehensive intervention time
      period compared to baseline (2.3%) or to the limited intervention time period
      (2.3%). Although there was no significant difference in the average cost per
      newborn readmitted across the three study time periods, during the comprehensive
      intervention time period the average costs of a NNR were significantly lower
      ($4,180, p = .041) for the intervention group compared to those who received no
      intervention ($5,338). There was a cost benefit of 513,540 dollars due to fewer
      readmissions during the comprehensive time period, but it did not exceed the cost
      of the intervention. CLINICAL IMPLICATIONS: Providing comprehensive follow-up for
      new mothers in the postpartum period can reduce NNRs, thus lowering the average
      newborn readmission costs for those who receive psychosocial support. Followup
      for new mothers should be an accepted norm rather than the exception in
      postpartum care, but NNRs should not be considered the sole outcome in such
      programs.

PMID- 20032759
TI  - Perceptions regarding oocyte donation in a group of female college students.
AB  - PURPOSE: To describe the perceptions of young female college students regarding
      oocyte donation (OD). METHODS: Descriptive survey of 330 female undergraduates.
      RESULTS: The subjects were primarily middle class, White, Christian, and lived in
      rural or suburban areas of upstate New York. The majority knew little about OD,
      but felt that the risk, time commitment, medications, and compensation would be
      most important in their decision to participate. Twenty-three percent would
      consider OD; 43% would most likely not consider it. Primary motivational factors
      for considering OD would be: helping another woman or couple (82%), and
      reimbursement for time and effort (11%). Deterring factors included medication
      and procedural risks (33%), lack of knowledge (30%), invasiveness of the process
      (21%), ethical reasons (7.5%), and religious reasons (6.5%). CLINICAL
      IMPLICATIONS: Young female college students are routinely targeted for oocyte
      donation. It is essential that nurses who work in university health settings,
      reproductive endocrinology, or other obstetrics/gynecology venues be educated
      about oocyte donation, and be ready to provide nonbiased, comprehensive, and
      current information to college-age women. Education for this group should include
      medication side effects, procedural risks, recipient characteristics, and ethical
      considerations such as disposition of embryos. Nursing educators should also
      consider adding OD as a contemporary topic in nursing school curricula.

PMID- 20032760
TI  - The lived experience of Jordanian women who received family support during labor.
AB  - PURPOSE: Policies regarding childbirth in Jordan currently exclude attendance by
      a female relative to provide support. This study was done in order to describe
      the experience of a group of Jordanian women who had been afforded support from a
      female relative during a nursing research project. DESIGN AND METHODS:
      Semistructured interviews were conducted with 25 women at 6 weeks postpartum. All
      of the women had given birth at the main hospital in the southern region of
      Jordan. FINDINGS: Women had positive experiences with their female relative
      support. Four themes were identified as common to the women involved: (1)
      increased sense of security, (2) provision of physical help, (3) communicating
      the woman's needs/wishes to her professional caregivers, and (4) emotional
      support and encouragement. CLINICAL IMPLICATIONS: The results show that the
      support of a female relative was helpful for this small group of Jordanian women
      experiencing their first labor and birth. Since the literature clearly shows that
      support in labor is appropriate and produces improved outcomes, public health
      practitioners in maternal and child health, along with hospitals, should
      emphasize this as a valuable resource for pregnant women. Non-Western or
      developing countries could benefit from more fully using evidence currently in
      the literature on a range of practices, including that of emotional and social
      support in labor.

PMID- 20032761
TI  - Securing the safety of our most precious cargo: SAFE KIDS.
AB  - There are staggering and tragic statistics involving children, car seats, and
      motor vehicle accidents. According to the Centers for Disease Control and
      Prevention, motor vehicle injuries are the leading cause of death among children
      from 0 to 15 years of age, and in the United States during 2005, 1,335 children
      ages 14 years and younger died as occupants in motor vehicle accidents;
      approximately 184,000 were injured. That is an average of 4 deaths and 504
      injuries each day. National Highway Traffic Safety Administration (NHTSA)
      statistics show that nearly one-half of deaths and injuries in children occurred
      because they were not properly restrained. Child safety seats and safety belts,
      when installed and used properly, can prevent injuries and save lives. Among
      children under age 5, an estimated 425 lives were saved in 2006 by child
      restraint use. Research on the effectiveness of child safety seats has found them
      to reduce fatal injury by 71% for infants, and by 54% for toddlers in passenger
      cars. This article discusses the need for increased education of parents and
      healthcare professionals about selection and installation of car safety
      restraints, and the importance of developing a child safety restraint program.

PMID- 20032762
TI  - Revised pregnancy weight gain recommendations.

PMID- 20032763
TI  - An educational resource for health information technology.

PMID- 20032765
TI  - Together we stand: Bolivian initiatives.

PMID- 20032766
TI  - Quality measures for perinatal care.

PMID- 20032767
TI  - Patient-specific internal radionuclide dosimetry.
AB  - The development of patient-specific treatment planning systems is of outmost
      importance in the development of radionuclide dosimetry, taking into account that
      quantitative three-dimensional nuclear medical imaging can be used in this
      regard. At present, the established method for dosimetry is based on the
      measurement of the biokinetics by serial gamma-camera scans, followed by
      calculations of the administered activity and the residence times, resulting in
      the radiation-absorbed doses of critical organs. However, the quantification of
      the activity in different organs from planar data is hampered by inaccurate
      attenuation and scatter correction as well as because of background and organ
      overlay. In contrast, dosimetry based on quantitative three-dimensional data can
      be more accurate and allows an individualized approach, provided that all effects
      that degrade the quantitative content of the images have been corrected for. In
      addition, inhomogeneous organ accumulation of the radionuclide can be detected
      and possibly taken into account. The aim of this work is to provide adequate
      information on internal emitter dosimetry and a state-of-the-art review of the
      current methodology and future trends.

PMID- 20032769
TI  - Detection of occult wrist fractures using quantitative scintigraphy.

PMID- 20032771
TI  - Antiretroviral monotherapy: should we abandon the principles of successful
      antiretroviral therapy?

PMID- 20032772
TI  - Oral uridine supplementation antagonizes the peripheral neuropathy and
      encephalopathy induced by antiretroviral nucleoside analogues.
AB  - OBJECTIVE: Peripheral neuropathy and central nervous system neurodegeneration may
      result from the mitochondrial toxicity of some antiretroviral nucleoside
      analogues. We investigated whether this neuropathology may be antagonized by
      uridine supplementation in vivo. DESIGN: Because of the obvious difficulties in
      obtaining human neural tissues, the mitochondrial neurotoxicity of the nucleoside
      analogues was studied in mice. METHODS: BALB/C mice (7 weeks of age) were fed for
      9 weeks with zalcitabine (13 mg/kg per day) or zidovudine (100 mg/kg per day)
      with or without mitocnol (340 mg/kg per day), a dietary supplement with high
      uridine bioavailability. Hippocampal and sciatic nerve mitochondria were
      analyzed. RESULTS: Zalcitabine and to a lesser extent zidovudine induced a
      significant peripheral neuropathy and encephalopathy with disrupted mitochondrial
      ultrastructure, depleted mitochondrial DNA, reduced levels of cytochrome c
      oxidase activity and diminished expression of mitochondrial DNA-encoded
      cytochrome c oxidase subunit I. Mitocnol had no intrinsic effects but attenuated
      or fully normalized all measured disorder of the peripheral and central nervous
      system. CONCLUSION: Zidovudine and zalcitabine induce a mitochondrial disorder in
      the peripheral and central nervous system, both of which are antagonized by
      uridine supplementation.

PMID- 20032773
TI  - An unusual cause of death at preschool age: scalding by hot milk.
AB  - Scalding is one of the most painful and devastating burn injuries a child can
      suffer. Victims are generally scalded by splashed or spilled hot fluids in the
      home environment. Interestingly, scalding by hot milk is a common cause of burns
      in rural parts of Turkey. This study aimed to identify the general features of
      scalding by hot milk, and to make the authorities aware of this problem through
      educational programs for parents and caregivers.The records of the Council of
      Forensic Medicine Adana Group Administration and public prosecutor's office were
      used. Forty-four deaths in children of preschool age (under 6) due to scalding by
      hot milk during 2001-2005 were analyzed.Scalding with hot milk constituted 1.05%
      of all medico-legal deaths (4183) during the period considered. Twenty-five
      (56.81%) of the victims were male while 19 (43.19%) were female. The victims'
      ages ranged between 18 months and 6 years, with a mean age of 3.03.Scalding by
      hot milk appears to be an important public health problem, especially in rural
      areas of Turkey. Educational programs for families and caregivers and
      implementation of simple safety measures will decrease the prevalence of deaths
      due to such preventable injuries.

PMID- 20032774
TI  - Chronic traumatic encephalopathy, suicides and parasuicides in professional
      American athletes: the role of the forensic pathologist.
AB  - We present 5 cases of professional American contact sport athletes who committed
      parasuicides and suicides aged 50, 45, 44, 36, and 40 years old. Full forensic
      autopsies and immunohistochemical analyses of the brains revealed chronic
      traumatic encephalopathy (CTE). The brains appeared grossly normal at autopsy
      without gross evidence of remote traumatic injuries or neurodegenerative disease.
      Brain immunohistochemical analyses revealed widespread cerebral taupathy in the
      form of neurofibrillary tangles and neuritic threads without neuritic amyloid
      plaques. CTE refers to chronic cognitive and neuropsychiatric symptoms of chronic
      neurodegeneration following a single episode of severe traumatic brain injury or
      repeated episodes of mild traumatic brain injury. CTE can only be definitively
      diagnosed by direct tissue examination. Without full autopsies and
      immunohistochemical brain analyses these cases would never have been identified.
      Forensic pathologists will play a vital and central role in the emerging disease
      surveillance of CTE in professional American athletes, in the identification of
      CTE cases, and in the establishment of the epidemiology of CTE, with the goal of
      eventually developing preventive and interventional therapeutic protocols for CTE
      outcomes.

PMID- 20032775
TI  - Sudden unexpected death due to left ventricular noncompaction of myocardium: case
      report and review of the literature.
AB  - Left ventricular noncompaction of the myocardium is a rare genetic cardiac
      disease characterized by a prominent meshwork and deep intertrabecular recesses
      of the left ventricle. The condition has frequently been misdiagnosed as other
      cardiomyopathies. Sudden deaths due to the disease are rarely reported in the
      literature of forensic sciences. We report 2 cases of sudden death due to
      undiagnosed left ventricular noncompaction. One was a 30-year-old man who
      suddenly collapsed while eating breakfast. He was pronounced dead on arrival at
      the hospital. The other 24-year-old man had a witness collapse at home. Despite
      immediate resuscitation, he expired 11 hours after hospitalization. Postmortem
      examination revealed that both patients died of left ventricular noncompaction.
      The key pathologic findings are described. Additionally, the literature is
      reviewed, and the incidence, clinical and pathophysiologic presentation,
      pathogenesis, and diagnostic criteria for the left ventricular noncompaction are
      discussed.

PMID- 20032776
TI  - Rupture of splenic artery aneurysm in pregnancy: a review of the literature and
      report of two cases.
AB  - BACKGROUND: Splenic artery aneurysms are an uncommon form of vascular disease,
      which have a significant potential for rupture, most commonly associated with
      pregnancy, typically presents as sudden, unexpected death. As a consequence, the
      initial recognition and diagnosis of splenic artery aneurysm rupture take place
      only at autopsy. CLINICAL CASES: This report presents 2 cases of sudden death
      resulting from splenic artery aneurysm in a pregnant woman and a postpartum
      woman, respectively. The former splenic artery aneurysm were measuring 1 cm in
      diameter and the latter splenic artery aneurysm 5.5 x 5 x 2 cm in size.
      Histologic examination of the both vessels wall showed severe morphologic changes
      of degeneration together with an attenuation of arterial internal elastica.
      CONCLUSIONS: To our knowledge, splenic artery aneurysm in pregnant woman is
      unusual vital disease. It is essential that obstetricians are alert to the
      prodromal and catastrophic symptoms of splenic artery aneurysm. Early recognition
      and prompt management, including early resected electively, are vital to the
      survival of both mother and fetus.

PMID- 20032777
TI  - NF-kappaB is involved in SHetA2 circumvention of TNF-alpha resistance, but not
      induction of intrinsic apoptosis.
AB  - Treatment of cancer with tumor necrosis factor-alpha (TNF-alpha) is hindered by
      resistance and toxicity. The flexible heteroarotinoid, SHetA2, sensitizes
      resistant ovarian cancer cells to TNF-alpha-induced extrinsic apoptosis, and also
      induces intrinsic apoptosis as a single agent. This study tested the hypothesis
      that nuclear factor-kappaB (NF-kappaB) is involved in SHetA2-regulated intrinsic
      and extrinsic apoptosis. SHetA2 inhibited basal and TNF-alpha-induced or hydrogen
      peroxide-induced NF-kappaB activity through counter-regulation of upstream kinase
      (IkappaB kinase) activity, inhibitor protein (IkappaB-alpha) phosphorylation, and
      p-65 NF-kappaB subunit nuclear translocation, but independently of reactive
      oxygen species generation. Ectopic over-expression of p-65, or treatment with TNF
      alpha receptor 1 (TNFR1) small interfering RNA or a caspase-8 inhibitor, each
      attenuated synergistic apoptosis by SHetA2 and TNF-alpha, but did not affect
      intrinsic apoptosis caused by SHetA2. In conclusion, NF-kappaB repression is
      involved in SHetA2 circumvention of resistance to TNF-alpha-induced extrinsic
      apoptosis, but not in SHetA2 induction of intrinsic apoptosis.

PMID- 20032779
TI  - Validation of three automatic devices for self-measurement of blood pressure
      according to the International Protocol: The Omron M3 Intellisense (HEM-7051-E),
      the Omron M2 Compact (HEM 7102-E), and the Omron R3-I Plus (HEM 6022-E).
AB  - OBJECTIVE: Three oscillometric devices for the self blood pressure measurement
      were evaluated according to the International Protocol of the European Society of
      Hypertension in three separate studies. The Omron M3 Intellisense and the Omron
      M2 Compact measures blood pressure (BP) at the brachial level; the Omron R3-I
      Plus measures BP at the wrist level. METHODS: The International Protocol is
      divided into two phases and includes a total number of 33 participants on whom
      the validation is performed. In each study, and for each participant, four BP
      measurements were taken simultaneously by two observers using mercury
      sphygmomanometers alternately with three measurements with the tested device. The
      difference between the observers and the device BP values was calculated for each
      measurement. The 99 pairs of BP differences were classified into three categories
      (< or =5, < or =10, < or =15 mmHg). RESULTS: All three tested devices passed the
      first and second phase of the validation process. The mean differences between
      the device and mercury readings were 1.9+/-3.0 and -1.0+/-2.3 mmHg for systolic
      and diastolic BP, respectively, for the Omron M3 Intellisense device, 2.5+/-5.4
      and -2.3+/-3.6 mmHg for the Omron M2 Compact device, and 1.4+/-4.5 and 0.8+/-4.6
      mmHg for the Omron R3-I Plus device. CONCLUSION: Readings of the Omron M3
      Intellisense, the Omron M2 Compact and the Omron R3-I Plus, differing by less
      than 5, 10, and 15 mmHg fulfill the International Protocol requirements and
      therefore can be used by patients for self blood pressure measurement.

PMID- 20032778
TI  - Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive
      surgery in patients with recurrent ovarian cancer: a phase I study.
AB  - BACKGROUND: Intraperitoneal (i.p.) epinephrine was shown to increase the
      accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a
      model of peritoneal carcinomatosis in rats. METHODS: To determine the tolerance
      to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma
      were intraoperatively treated in this phase 1 study. After maximal cytoreductive
      surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin
      and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline
      solution at 37 degrees C. RESULTS: No deaths occurred. Three patients were
      treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events.
      Two of the three patients who received 3 mg/l epinephrine experienced cardiac
      intolerance. Six additional patients received 2 mg/l of epinephrine without
      toxicity. A relationship between the serum concentration of epinephrine and
      occurrence of cardiac toxicity was established. A 60% decrease in serum area
      under the curve of platinum was calculated in patients receiving i.p. epinephrine
      compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not
      increased by epinephrine. No haematological or neurological toxicity was
      recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis
      (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually
      reported for this heavy surgical procedure. CONCLUSION: The combination of i.p.
      epinephrine with cisplatin as intraoperative chemotherapy after optimal
      cytoreductive surgery is feasible. The recommended concentration for further
      studies is 2 mg/l for i.p. epinephrine.

PMID- 20032780
TI  - GAPO syndrome: a case associated with bilateral interstitial keratitis and
      hypothyroidism.

PMID- 20032781
TI  - Fibular hemimelia with polysyndactyly: a case report.

PMID- 20032782
TI  - Do indication and demographics for colonoscopy affect completion? A large
      national database evaluation.
AB  - BACKGROUND AND AIM: Indication for colonoscopy has not been examined as a
      predictor of colonoscopy completion. We hypothesized that colonoscopy conducted
      for colorectal cancer screening might have higher in completion rates than
      colonoscopy conducted for other indications. METHODS: The study design was a
      retrospective cohort. Colonoscopies recorded within the Clinical Outcomes
      Research Initiative database conducted between 1 January 2002 and 30 June 2003
      were analyzed. Indication included: average-risk screening; surveillance;
      nonspecific abdominal symptoms; bleeding symptoms; or family history of
      colorectal carcinoma. Demographic factors and indication for colonoscopy were
      evaluated for the outcome of incomplete colonoscopy using logistic regression
      analysis. RESULTS: 129 549 Colonoscopy procedures were analyzed. Average risk
      screening seemed to be protective for completion (relative risk: 0.69; 95%
      confidence interval: 0.63-0.75). Bleeding and nonspecific symptoms had higher
      risk of incomplete procedure compared to other indications. Males had higher
      completion rates compared to females (relative risk: 0.62; 95% confidence
      interval: 0.58-0.66). Community setting had higher completion rates compared to
      academic or Veteran's administration sites. Increasing age was associated with
      higher rate of incomplete colonoscopy. CONCLUSION: Colonoscopy conducted for
      screening indication has comparable completion rates when compared with other
      indications. An overall completion rate of around 95% was noted in this study.
      This is the largest study to date verifying that completion rates are meeting
      recommended multisociety guidelines in the USA. Nonspecific abdominal symptoms in
      Caucasian population, female sex, advanced age, clinical setting, and ethnic
      groups African-American and Hispanic were found to have increased risk of
      incomplete procedure.

PMID- 20032783
TI  - HIV replication capacity is an independent predictor of disease progression in
      persons with untreated chronic HIV infection.
AB  - OBJECTIVE: To assess the effect of pol replication capacity (RC) on the hazard
      ratio of progression to a composite endpoint of time to progression to <350 CD4+
      cells per microliter, initiation of therapy, or death. METHODS: pol RC assays
      were performed after study closure in baseline samples obtained from 316
      enrollees in a prospectively monitored cohort of treatment-naive adults with
      >or=450 CD4+ cells per microliter and >or=1000 HIV-1 RNA copies per milliliter.
      RESULTS: The median RC was 79%. Patients with a lower RC had a lower median viral
      load (4.0 vs 4.2 Log HIV-1 RNA copies/mL, P = 0.026) and a lower rate of protease
      inhibitor resistance 2% vs 8%, P = 0.03). Otherwise, baseline demographic and
      laboratory characteristics were similar. The hazard ratio of progression to the
      composite endpoint was 0.73 (P = 0.041) for persons with lower RC, 2.07 per 1.0
      log10 higher viral load (P < 0.001), and 0.86 per 50 cells per microliter higher
      CD4+ cell count (P < 0.001). The effect of lower RC was also significant in a
      separate analysis of time to initiation of therapy (P = 0.04). CONCLUSIONS: These
      results show that untreated patients with lower vs higher RC had a slower rate of
      progression as assessed by a composite outcome of time to CD4+ count <or=350
      cells per microliter, treatment initiation, or death.

PMID- 20032784
TI  - Hepatitis B and hepatitis C seroprevalence in children receiving antiretroviral
      therapy for human immunodeficiency virus-1 infection in China, 2005-2009.
AB  - BACKGROUND: Coinfection of hepatitis B virus (HBV) or hepatitis C virus (HCV) may
      compromise pediatric antiretroviral therapy (ART) in China. In this study, we
      evaluated the seroprevalence of HBV and HCV in children receiving ART and
      associated factors. METHODS: Patients were selected from HIV-1-infected children
      under age 16 enrolled in China National Pediatric ART Cohort since July 2005.
      Medical assessments, hepatitis B surface antigen (HBsAg), and anti-HCV antibody
      serologies, and transaminase levels were obtained for analysis. RESULTS: A total
      of 53 of 1082 children tested were HBsAg seropositive [4.9%; 95% confidence
      interval (CI): 3.6% to 6.2%], and 90 of 938 children tested were anti-HCV
      antibody positive (9.6%; 95% CI: 7.7% to 11.5%). No other serologic assays were
      performed for HBV detection. Age was associated with HBV coinfection in
      univariate analysis; older children were more likely to be HBsAg positive.
      Multivariate analysis revealed that children infected with HIV through
      transfusion of contaminated blood or blood products were more likely to be anti
      HCV antibody positive than those infected with HIV through other routes (adjusted
      odds ratio = 6.2; 95% CI: 3.3% to 11.7%). CONCLUSIONS: The high prevalence of HBV
      and HCV coinfection in HIV-infected children in China receiving ART demands
      routine screening for viral hepatitis coinfection, intensive prevention of
      childhood HBV and HCV transmission, and modification of the management of
      pediatric HIV infection.

PMID- 20032785
TI  - Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir,
      each in combination with tenofovir and emtricitabine, for management of
      antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results
      of the CASTLE study.
AB  - BACKGROUND: Once-daily atazanavir/ritonavir demonstrated similar antiviral
      efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less
      gastrointestinal disturbance and a better lipid profile, in treatment-naive
      patients. METHODS: International, multicenter, open-label, 96-week noninferiority
      randomized trial of atazanavir/ritonavir 300/100 mg once daily vs
      lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose
      tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1
      infected patients. The primary end point was the proportion of patients with HIV
      RNA <50 copies/mL at 48 weeks. Results through 96 weeks are reported. RESULTS: Of
      883 patients enrolled, 440 were randomized to atazanavir/ritonavir and 443 to
      lopinavir/ritonavir. At week 96, more patients receiving atazanavir/ritonavir
      achieved HIV RNA <50 copies/mL (74% vs 68%, P < 0.05) in the intent-to-treat
      analysis. On both regimens, 7% of subjects were virologic failures by 96 weeks.
      Bilirubin-associated disorders were greater in patients taking
      atazanavir/ritonavir. Treatment-related gastrointestinal adverse events were
      greater in patients taking lopinavir/ritonavir. Mean changes from baseline in
      fasting total cholesterol, non-high-density lipoprotein cholesterol, and
      triglycerides at week 96 were significantly higher with lopinavir/ritonavir (P <
      0.0001). CONCLUSIONS: Noninferiority of atazanavir/ritonavir to
      lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better
      lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir.

PMID- 20032786
TI  - Neuromuscular electrical stimulation and inspiratory muscle training as potential
      adjunctive rehabilitation options for patients with heart failure.
AB  - Aerobic and resistance exercise training programs produce an abundance of
      physiologic and clinical benefits in patients with heart failure (HF). Improved
      maximal aerobic capacity, submaximal aerobic endurance, muscle force production,
      perceived quality of life, and skeletal muscle characteristics are among the more
      established outcomes resulting from these rehabilitation techniques. Moreover,
      both aerobic and resistance exercise training appear to portend a low risk to
      patients with HF when appropriate exercise prescription methods are followed.
      While the aforementioned training techniques will undoubtedly continue to be at
      the center of a well-formulated rehabilitation program, other adjunctive
      interventions, which are presently underutilized in clinical practice, may prove
      beneficial in patients with HF. Specifically, both neuromuscular electrical
      stimulation (NMES) and inspiratory muscle training (IMT) appear to significantly
      improve several physiologic, exercise, symptomatologic, and quality-of-life
      parameters. NMES targets skeletal muscle abnormalities, whereas IMT primarily
      targets the weakened respiratory musculature, both often encountered in patients
      with HF. A PubMed search using relevant key words identified 19 original
      investigations examining the impact of NMES (13 studies) and IMT (6 studies)
      training programs in patients with HF. The resultant review (1) provides a
      summary of the original research outcomes of both NMES and IMT in patients with
      HF; (2) addresses current research gaps, providing a direction for future
      investigations; and (3) provides clinical scenarios where NMES and IMT may prove
      to be beneficial during the rehabilitation of patients with HF.

PMID- 20032787
TI  - The effects of sex and method of blood pressure measurement on genetic
      associations with blood pressure in the PAMELA study.
AB  - BACKGROUND: Phenotypic accuracy and specificity are essential for a successful
      genetic association study. Blood pressure (BP) measurements show heterogeneity
      depending on the method and time of measurement, sexual dimorphism and
      measurement errors, making genetic dissection difficult. METHODS AND RESULTS: We
      studied 1550 adults aged 25-74 years, not on any antihypertensive treatment,
      resident in Monza, Italy (PAMELA study) all of whom had home, clinic and
      ambulatory BPs measured. We analysed 3705 single nucleotide polymorphisms (SNPs)
      (1324 typed and 2381 imputed) across 168 genes for association with these traits.
      No SNP achieved an experiment wide significance level of P less than 3 x 10 for
      any of the phenotypes studied. We selected 28 top candidate SNPs for further
      analysis of phenotypic heterogeneity and sexual dimorphism using a gene-centric
      strategy calculating empirical P values by permutations within each gene by
      including genic SNPs with an r less than 0.5. The association signals were not
      consistent across all the BP phenotypes, whether compared by genes or by
      physiological pathways. The top SNPs in WNK1, ADRA1A, ADRA1B, DRD1, NOS1 and PON3
      showed significant sex interaction for BP and when analysed separately by sex
      showed evidence of dimorphism with opposite direction of effect for the same
      allele in the two sexes. CONCLUSION: In the largest study of its kind, we show
      that sex and BP measurement methods have a significant impact on association
      signals. These findings might explain previous inconsistencies in studies on
      cardiovascular candidate genes and should have major implications for the design
      and interpretation of association studies.

PMID- 20032788
TI  - Circulating microparticles may influence early carotid artery remodeling.
AB  - OBJECTIVES: To test associations of circulating microparticles with large artery
      remodeling before atherosclerosis is detectable. METHODS: In 232 untreated
      symptom-free individuals, we measured microparticles of various cellular origins
      (platelet, endothelial and leukocyte) by specific anti-GPIb (glycoprotein Ib),
      anti-cluster of differentiation (CD) 105 and anti-CD11a antibodies, and common
      carotid artery intima-media thickness (IMT), internal and external diameters by
      ultrasound. RESULTS: Except for CD105 microparticles with IMT to lumen ratio
      (IMT/D, P < 0.05), microparticles correlated with no carotid dimensions.
      Significant interactions existed between each microparticle type and IMT on
      internal and external diameters (GPIb, P < 0.01; CD105 and CD11a microparticles P
      < 0.001) consisting of lower trend in increased diameter with increasing IMT in
      individuals with high than in those with low microparticle level (according to
      the median) of each origin. As a result, individuals within the third IMT tertile
      had lower internal diameter in the presence of high than in the presence of low
      level of GPIb, CD105 or CD11a microparticles (P = 0.001, <0.05 or 0.01,
      respectively), and lower external diameter in the presence of high than in the
      presence of low level of GPIb and CD11a microparticles (P = 0.001 and 0.01).
      Also, individuals within third IMT tertile exhibited positive correlations of IMT
      with CD105 and CD11a microparticles (P < 0.05), negative correlations of internal
      diameter with GPIb (P < 0.05), CD105 (P < 0.05) and CD11a microparticles (P <
      0.01) and of external diameter with GPIb and CD11a microparticles (P < 0.05), and
      positive correlations of IMT/D with CD105 and CD11a microparticles (P < 0.001).
      CONCLUSION: Increased levels of leukocyte and endothelial-derived microparticles
      are associated with carotid inward remodeling in individuals with the greatest
      IMT before atherosclerosis is detectable.

PMID- 20032790
TI  - Intensive insulin therapy in severe traumatic brain injury: a randomized trial.
AB  - BACKGROUND: Intensive insulin therapy (IIT) has been shown to reduce morbidity
      and mortality in critically ill patients. Little investigation has been done to
      find out whether it improves the prognosis of patients with severe traumatic
      brain injury (STBI). METHODS: We conducted a prospective controlled study where
      adult patients with blunt STBI, with Glasgow Coma Scale <or=8, admitted to the
      intensive care unit (ICU) were randomly assigned to receive either IIT
      (maintenance of blood glucose between 80 mg/dL and 110 mg/dL with continuous
      insulin infusion) or conventional glycemic therapy (CGT) (maintenance of blood
      glucose below 180 mg/dL with subcutaneous insulin and insulin infusion only if
      blood glucose levels exceeded 220 mg/dL). The main outcome was Glasgow outcome
      scale 6 months after trauma. Secondary measures were hypoglycemia, incidence of
      infections, and days in ICU. RESULTS: Of the 88 patients randomized, 42 were
      assigned to IIT and 46 to CGT. There was no difference (p = 0.63) in neurologic
      outcomes between the treatment groups: Glasgow outcome scale >3 was observed in
      16 patients (41%) in the IIT and in 13 patients (32.5%) in the CGT group. More
      patients in the IIT group had hypoglycemia: 32 (82.1%), compared with 7 (17.5%)
      in the CGT group (p < 0.001). There were no differences in the number of days
      spent in the ICU (18.2 +/- 27.6 vs. 12.9 +/- 12.7) or in the sepsis rates (84.6%
      vs. 80%) between the groups. CONCLUSION: In our study, IIT did not improve the
      neurologic outcome of patients with STBI but did increase the risk of
      hypoglycemia compared with CGT.

PMID- 20032789
TI  - Safety and efficacy of combining sunitinib with bevacizumab +
      paclitaxel/carboplatin in non-small cell lung cancer.
AB  - INTRODUCTION: Bevacizumab (B) improves survival of patients with metastatic,
      nonsquamous non-small cell lung cancer. Based on encouraging results from
      preclinical studies combining B with sunitinib (S), a phase II, randomized, open
      label study (Study Assessing the Blockade of both VEGF Receptor and ligand to
      enhance Efficacy in Lung) was initiated to assess clinical outcomes of adding S
      to paclitaxel (P)/carboplatin (C) + B (PCB) for first-line treatment of locally
      advanced, metastatic, or recurrent nonsquamous non-small cell lung cancer.
      METHODS: Study enrollment was to occur in three phases. In the first phase,
      patients received PC + B (15 mg/kg every 3 weeks), +/-S (25 mg daily, 2 weeks on,
      1 week off). If tolerated, the second phase would include a third cohort
      receiving 37.5 mg S. The third phase would consist of PCB +/- highest tolerable
      dose S. RESULTS: Between March 2007 and January 2008, 26 patients were randomized
      to receive PCB and 30 to PCB + S 25 mg. Because of poor tolerability, none of the
      patients were escalated to 37.5 mg S. Median treatment duration was 10.3 weeks
      for PCB and 6.0 weeks for PCB + S. Thirty-five percent of patients on PCB + S
      required S dose reduction, 52% required S treatment interruption, and 59%
      discontinued S because of adverse events, most frequently hematologic events
      (neutropenia, thrombocytopenia, and leukopenia) and fatigue. Patients receiving
      PCB + S required more B interruptions (38% versus 19% for PCB) and
      discontinuation (52% versus 35%) because of adverse events. Survival data were
      limited by small sample sizes and limited treatment duration. Overall survival
      was not mature at time of analysis: median 6.6 months for PCB + S and not reached
      for PCB. Two out of 25 efficacy-evaluable patients randomized to the PCB + S
      cohort had confirmed partial responses, compared with 5 of 19 randomized to the
      PCB cohort. CONCLUSIONS: The addition of S to PCB was not well tolerated because
      of toxicities. This combination should not be studied further at these doses and
      schedules.

PMID- 20032791
TI  - rFVIIa and NN1731 reduce bleeding in hydroxyethyl starch hemodiluted rabbits.
AB  - BACKGROUND: Colloid plasma expanders are used to maintain blood pressure and
      ensure tissue perfusion during hypovolemia, e.g., caused by traumatic bleeding.
      Although colloids stabilize the cardiovascular system, they can also potentially
      cause coagulopathy. Consequently, bleeding tendency may increase, as well as the
      associated risk of morbidity and mortality. Thus, there is a need for hemostatic
      treatment options for these patients. rFVIIa (NovoSeven, Novo Nordisk A/S,
      Bagsvaerd, Denmark) is a hemostatic agent that effectively controls bleedings in
      patients with inhibitor-complicated hemophilia. rFVIIa works by enhancing
      thrombin generation on the activated platelet surface at the site of injury,
      leading to the formation of a stable fibrin clot. NN1731 is an rFVIIa analog with
      increased hemostatic potential and is currently under clinical development.
      METHODS: In this study, the effect of rFVIIa and NN1731 on cuticle bleeding in
      rabbits 50% hemodiluted with hydroxyethyl starch (molecular weight ~ 200,000) was
      tested. Cuticle bleeding was induced after a two-stage hemodilution procedure.
      After 5 minutes, the animals were treated with rFVIIa (2, 5, or 10 mg/kg), NN1731
      (1 or 2 mg/kg), or vehicle, followed by 30 minutes of observation. RESULTS:
      Hemodilution caused a significant increase in bleeding time and blood loss.
      rFVIIa dose-dependently reduced bleeding time and blood loss, reaching
      statistical significance at 10 mg/kg. However, 2 mg/kg NN1731 reduced bleeding
      time and blood loss significantly and to a similar extent as 10 mg/kg rFVIIa.
      This increased hemostatic potential of NN1731 compared with rFVIIa and was
      confirmed by findings using thromboelastography on ex vivo hemodiluted whole
      blood. CONCLUSION: In summary, rFVIIa and NN1731 significantly and dose
      dependently reduced bleeding in extensively hemodiluted rabbits.

PMID- 20032793
TI  - The effect of surgical timing on functional outcomes of traumatic facial nerve
      paralysis.
AB  - BACKGROUND: The optimal timing for surgical exploration of traumatic facial
      paralysis to best preserve facial function is currently controversial. This
      article reviews the final outcomes of facial function in patients with traumatic
      intratemporal facial nerve injury according to the timing of surgical
      exploration. METHODS: We performed a retrospective review of 58 patients with
      complete facial nerve paralysis caused by temporal bone fractures as a result of
      head trauma between 1998 and 2007. Patients were divided into three groups
      according to the type of trauma. The only difference between patients in each
      group was the timing of the surgical exploration. Characteristics assessed in the
      study included type of trauma, location of facial nerve injury, timing of
      surgical intervention, audiometric findings, surgical approach, and long-term
      follow-up of recovery of facial nerve function, as assessed by two facial nerve
      grading systems. RESULTS: The final functional gains in early-operated patients
      were 3.7 +/- 0.59 on the House-Brackmann (HB) scale and 75.6 +/- 10.88 on the
      Sunnybrook scale. The outcome in late-operated patients was 2.17 +/- 0.52 on the
      HB scale and 34.7 +/- 16.95 on the Sunnybrook scale, and that of nonoperated
      patients was 2.0 +/- 0.63 on the HB scale and 26.8 +/- 6.27 on the Sunnybrook
      scale. CONCLUSION: This study demonstrated that some patients with traumatic
      facial nerve paralysis who had nerve conduction studies consistent with a poor
      prognosis regained considerable facial function after early surgical
      intervention. However, late exploration after facial nerve paralysis did not
      result in positive outcomes, regardless of the type of temporal bone fracture or
      the site of injury, and no difference was observed compared with conservative
      treatment.

PMID- 20032792
TI  - Measurable outcomes of quality improvement using a daily quality rounds
      checklist: one-year analysis in a trauma intensive care unit with sustained
      ventilator-associated pneumonia reduction.
AB  - BACKGROUND: We have previously demonstrated that the use of a daily "Quality
      Rounds Checklist" (QRC) can increase compliance with evidence-based prophylactic
      measures and decrease complications in a busy trauma intensive care unit (ICU)
      over a 3-month period. This study was designed to determine the sustainability of
      QRC use over 1 year and examine the relationship between compliance and outcome
      improvement. METHODS: A prospective before-after design was used to examine the
      effectiveness of the QRC tool in documenting compliance with 16 prophylactic
      measures for ventilator-associated pneumonia (VAP), deep venous thrombosis,
      pulmonary embolism, catheter-related bloodstream infection, and other ICU
      complications. The QRC was implemented on a daily basis for a 1-year period by
      the ICU fellow on duty. Monthly compliance rates were assessed by a
      multidisciplinary team for development of strategies for real-time improvement.
      Compliance and outcomes were captured over 1 year of QRC use. RESULTS: QRC use
      was associated with a sustained improvement of VAP bundle and other compliance
      measures over a year of use. After multivariable analysis adjusting for age (>
      55), injury mechanism, Glasgow Coma Scale score (<= 8), and Injury Severity Score
      (> 20), the rate of VAP was significantly lower after QRC use, with an adjusted
      mean difference of -6.65 (per 1,000 device days; 95% confidence interval, -9.27
      to -4.04; p = 0.008). During the year of QRC use, 3% of patients developed a VAP
      if all four daily bundle measures were met for the duration of ICU stay versus
      14% in those with partial compliance (p = 0.04). The overall VAP rate with full
      compliance was 5.29 versus 9.23 (per 1,000 device days) with partial compliance.
      Compared with the previous year, a 24% decrease in the number of pneumonias was
      recorded for the year of QRC use, representing an estimated cost savings of
      approximately $400,000. CONCLUSION: The use of a QRC facilitates sustainable
      improvement in compliance rates for clinically significant prophylactic measures
      in a busy Level I trauma ICU. The daily use of the QRC, requiring just a few
      minutes per patient to complete, equates to cost-effective improvement in patient
      outcomes.

PMID- 20032794
TI  - Epidemiology of tree stand-related injuries in the United States from 2000 to
      2007.
AB  - BACKGROUND: : Tree stands have remained popular among hunters because of the
      increased vantage point for the hunter. Although stand styles vary, the typical
      stand is very minimalistic in design, comprising a seat and an area for the
      hunter to place his feet. Although there have been studies using state trauma
      registry data, to date, there has not been a study on the epidemiology of tree
      stand-related injuries in the national population. METHODS: : The 2000 to 2007
      National Electronic Surveillance System provided information among individuals
      aged 16 years and older regarding tree stand-related injuries that required
      emergency room attention in the United States. Hunter population estimates from
      the U.S. Fish and Wildlife Services were used to estimates injury rates by sex,
      age, race, month, and year. RESULTS: : The rate of tree stand-related injuries
      remained relatively stable from 2000 to 2007. Rates were higher for men compared
      with women (48.0 vs. 24.7 per 100,000 hunters, respectively) and highest among
      those 15 to 24 (55.7 per 100,000) and 25 to 34 (61.0 per 100,000). CONCLUSIONS: :
      Although a majority of hunters are older, the highest rates occurred among the
      younger ones. Hunters using and manufacturers of tree stands must be aware of the
      safety precautions during use of the stands. Improvements in the safety design of
      the stands as well as knowledge to the proper use of stands can help to minimize
      the burden of injury in the hunter population related to tree stands.

PMID- 20032795
TI  - Conducted electrical weapon use by law enforcement: an evaluation of safety and
      injury.
AB  - INTRODUCTION: Controversy persists over the safety of conducted electrical
      weapons (CEWs), which are increasingly used by law enforcement agencies around
      the world. The purpose of this study was to examine injury patterns and
      physiologic conditions after CEW use under real life conditions. METHODS: A
      retrospective, cohort design was used, examining all CEW uses by one police
      department during a 6-year period. Data were collected from use-of-force forms
      and medical records and included conditions surrounding the use of force, medical
      histories, and data from emergency department evaluations and hospital
      admissions. RESULTS: Of 1,101 individuals subjected to (Taser M26 and X26) CEW
      use during the study period, 92.6% were male, the average body mass index was
      26.2, and the age range was 9 to 73 years. Of the 886 (80.5%) with medical
      records, 46.8% had a psychiatric history and 72.9% had a substance abuse history.
      Emergency department (ED) evaluations occurred for 295 (26.8%) incidents. Of
      chief complaints, 41.7% were trauma related, 26.8% were for altered mental
      status, and 21.7% were for psychiatric evaluation. On presentation, 17.6% had a
      pulse >120, 1.7% were febrile, and 30.9% were altered; 1.4% met criteria
      associated with "excited delirium." When laboratory workup occurred, 70.6% had
      positive urine toxicology and 44.8% had positive alcohol levels. Troponin I was
      positive for one patient. Other laboratory abnormalities were rare, although
      extensive evaluations were infrequently done. Admission occurred in 24.4% of ED
      presentations (6.5% of all subjects); of discharge diagnoses for these patients,
      59.7% were psychiatric, 22.2% were for unrelated trauma, 11.1% were for restraint
      related trauma, and 6.9% were for unrelated medical diagnoses. No patients died.
      CONCLUSIONS: Significant injuries related to 6 years of law enforcement CEW use
      in one city were rare. A large percentage of those subjected to CEW use had
      diagnoses of substance abuse and/or psychiatric conditions. Most admissions after
      CEW use were unrelated to law enforcement restraint.

PMID- 20032796
TI  - Surgical and survival outcomes in older women with endometrial cancer treated by
      laparoscopy.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility and safety of
      laparoscopic surgical management of apparently early-stage endometrial cancer in
      older women and to compare clinical outcomes between older and younger women.
      METHODS: Our prospective oncological database was retrospectively reviewed to
      identify all consecutive women who underwent surgery for endometrial cancer from
      2002. Data available included information about demography, comorbidities,
      surgical outcomes, histology, adjuvant therapies, and follow-up. Women were
      divided in two groups according to age (older, >65 y, and younger, < or =65 y).
      Univariate and multivariate analyses were performed to identify factors that
      negatively impact disease-free and overall survival. RESULTS: A total of 48
      (44.4%) older and 60 (55.6%) younger women were included. Groups were comparable
      in operative time, blood loss, need for blood transfusions, nodal count, and
      intraoperative and postoperative complications. Cancer in older women was more
      frequently upstaged than that in younger women (17 [35.4%] vs 8 [13.3%],
      respectively; P = 0.01). The 2- and 5-year disease-free survival rates were 82%
      versus 96% (P = 0.003) and 74% versus 93% (P = 0.0005) and the overall 2- and 5
      year survival rates were 87% versus 98% (P = 0.006) and 83% versus 95% (P = 0.01)
      for older and younger women, respectively. Multivariate analysis showed that
      advanced surgical stage, unfavorable histology, high-grade tumors (grade 3), and
      deep myometrial invasion (>50%) are independent risk factors for recurrence.
      CONCLUSIONS: In the absence of absolute anesthesia contraindications, laparoscopy
      seems to be feasible and safe in older women with endometrial cancer.
      Comprehensive surgical staging should be offered, regardless of age, to avoid
      understaging and to optimize treatment strategies.

PMID- 20032797
TI  - Prevention of coronary heart disease and osteoporosis in women aged 45 to 49
      years: a challenging role for general practitioners.
AB  - OBJECTIVE: Part of the risks for coronary heart disease (CHD) and osteoporosis in
      women are established by their lifestyle in the premenopausal period. Therefore,
      we assessed the risk of women aged 45 to 49 years for CHD and osteoporosis and
      its relation with socioeconomic status (SES) and access to general practitioners
      (GPs) to provide clues for prevention. METHODS: The health interview data used
      for this study originated from the second Dutch National Survey of General
      Practice, a study with a response rate of 64.5%. We studied SES, risk factors for
      CHD and osteoporosis, and access to GPs in women aged 45 to 49 years. RESULTS:
      The data of 571 women aged 45 to 49 years were included. A total of 39% had an
      increased risk for developing CHD in the next 10 years, and 3% had a high risk. A
      total of 22% had an increased risk for osteoporosis. We found a significant
      relation between SES and unhealthy lifestyle. An unhealthy lifestyle led to an
      increased or high risk for CHD, and a high osteoporosis risk. We did not find a
      significant relation between SES and GP consultation frequency. CONCLUSIONS:
      Special attention is required for women with the lowest SES because they have an
      unhealthier lifestyle than do women with middle or the highest SES. The group of
      women at higher risk for CHD and osteoporosis consulted their GP with the same
      frequency as did women at lower risk. The Dutch GP seems to be in an ideal
      position to play a role in the prevention of CHD and osteoporosis in
      premenopausal women because access to GPs is not influenced by SES.

PMID- 20032798
TI  - Ospemifene effectively treats vulvovaginal atrophy in postmenopausal women:
      results from a pivotal phase 3 study.
AB  - OBJECTIVE: The aim of this study was to study the efficacy and safety of
      ospemifene, a new selective estrogen receptor modulator, in the treatment of
      vulvovaginal atrophy in postmenopausal women. METHODS: A randomized, double-blind
      phase 3 study in which 826 postmenopausal women were randomized 1:1:1 to receive
      treatment with ospemifene 30 or 60 mg/day or placebo orally for 12 weeks was
      conducted. The primary inclusion criteria were having 5% or less superficial
      cells on the vaginal smear (maturation index), vaginal pH greater than 5.0, and
      at least one moderate or severe symptom of vulvovaginal atrophy. The four
      coprimary endpoints were the change from baseline to 12 weeks in the percentage
      of superficial and parabasal cells on the vaginal smear, change in vaginal pH,
      and change in severity of most bothersome symptom (vaginal dryness or
      dyspareunia) compared with placebo. All participants were given a nonhormonal
      vaginal lubricant for use as needed. RESULTS: Ospemifene was statistically
      significantly superior to placebo in each of the coprimary endpoints at the 60-mg
      dose. Statistically significant results were achieved for all coprimary endpoints
      with the 30-mg dose except for dyspareunia. Ospemifene was well tolerated at both
      doses and demonstrated a favorable safety profile. CONCLUSIONS: Ospemifene was
      shown to be effective and well tolerated for the treatment of the symptoms of
      vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and
      above the use of provided lubricants.

PMID- 20032799
TI  - The effects of raloxifene on mammographic breast density: a review of clinical
      trials.
AB  - OBJECTIVE: Breast density is an independent risk factor for the development of
      invasive breast cancer (BC). It has been hypothesized that because raloxifene
      (RLX) has been shown to reduce BC risk, its use will result in reduced breast
      density. METHODS: This article provides a review of seven clinical studies that
      examined the effects of RLX on breast density. RESULTS: Overall, RLX did not
      increase or decrease mammographic breast density. This article provides a review
      of the various methods used to determine breast density in these RLX studies and
      offers a potential explanation as to why the studies failed to show an effect on
      mammographic density. CONCLUSIONS: Presently, no clinical recommendations can be
      made with regard to RLX and its effects on breast density. To determine the
      effect of RLX on breast density, larger studies need to be conducted in
      postmenopausal women with high breast density at baseline who are at high risk
      for BC, with a standardized method of breast density measurement.

PMID- 20032800
TI  - False-positive F-18 FDG uptake in PET/CT studies in pediatric patients with
      abdominal Burkitt's lymphoma.
AB  - INTRODUCTION: In pediatric patients with abdominal Burkitt's lymphoma, the
      involvement of the gastrointestinal tract and abdominal lymph nodes are the main
      presenting feature of the disease. Chemotherapy is the main treatment modality
      and could be preceded by surgical excision of the abdominal masses. To achieve
      cure or long-term disease-free survival a balance has to be struck between
      aggressive chemotherapy and the probability of tumor necrosis secondary to
      treatment complicated by acute infections, perforation or intestinal bleeding. F
      18 fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG
      PET/CT) has been recommended over conventional imaging modalities for the follow
      up of these patients and for monitoring treatment response. As the incidences of
      postchemotherapy complications are high, the positive predictive value of PET/CT
      studies in these patients is very low and the false-positive rate is high from
      acute infections and tumor necrosis. Accordingly, histopathological confirmation
      of positive lesions on F-18 FDG-PET/CT studies is essential. This is especially
      important as post-therapy complications might present with nonspecific and
      nonurgent symptoms. At the same time initiating a second course of salvage
      chemotherapy is risky. AIM OF STUDY: Retrospectively reviewed F-18 FDG-PET/CT
      studies for 28 pediatric patients with abdominal Burkitt's lymphoma and diffuse
      large B-cell lymphoma after their treatment with chemotherapy or surgery.
      RESULTS: Four positive studies were found. All had pathological verification and
      were because of acute inflammation and tumor necrosis and there was no evidence
      of viable tumor cells. One patient had multiple recurrent lesions in the abdomen
      after the initial surgical excision and before starting chemotherapy. The
      incidence of acute complications in this series is 10.7%. CONCLUSION: This study
      confirms the high incidence of tumor necrosis and inflammation after chemotherapy
      for the abdominal Burkitt's lymphoma and consequently, the incidence of true
      positive F-18 FDG studies is low. This necessitates the need for
      histopathological confirmation of positive studies.

PMID- 20032801
TI  - Investigation of 18F-FDG 3D mode PET image quality versus acquisition time.
AB  - OBJECTIVE: Three-dimensional (3D) mode positron emission tomography (PET) is
      being used increasingly for clinical PET imaging. However, as yet, optimal
      acquisition parameters have not been established. The aim of this study was to
      investigate the effect of varying acquisition time on 3D image quality using
      standard clinical activities of F-fluorodeoxyglucose (FDG). METHODS: F-FDG
      phantom and patient PET images were acquired with varying acquisition times on a
      GE Discovery-STE PET/CT system. The NEMA Image-Quality phantom was imaged with
      four hot lesions in a uniform background. Images were acquired for 1, 2, 3, 4,
      and 5-min frames with three different lesion-to-background contrast ratios.
      Patient data were investigated using list mode acquisition to obtain comparable
      2, 3, and 4-min frames. Qualitative analysis involved grading image quality and
      lesion detectability. Quantitative analysis of phantom images involved assessing
      the coefficient of variation (COV) of background areas as a measure of noise, and
      lesion over background variability as a measure of image quality. Patient data
      were also assessed using COV analysis of liver uptake. RESULTS: Qualitative and
      quantitative analysis showed no significant difference in image quality between 4
      and 5-min acquisition frames for 3D mode F-FDG PET imaging with standard clinical
      activities. The observers noted no difference in perceived image quality. This
      finding was supported by COV analysis. CONCLUSION: This study shows that GE
      Discovery-STE acquisition frame time can be reduced to 3 min for standard 3D mode
      imaging at standard clinical activities of F-FDG.

PMID- 20032802
TI  - Acquiring diagnostic DaTSCAN images in claustrophobic or difficult patients using
      a 180 degrees configuration.
AB  - BACKGROUND: In this study, we have investigated the feasibility of a 180 degrees
      DaTSCAN brain SPECT acquisition. This technique has the advantage of being 'open
      view' for the patient and therefore more acceptable for claustrophobic patients.
      It also enables easier access for a technologist to hold the patient's head
      during acquisition to reduce movement in confused patients or in those with
      severe tremor. METHODS: In the first part of this study, we validated the
      practicality and image quality of a 180 degrees acquisition using a DaTSCAN
      Alderson head phantom with different camera configurations on GE Infinia and
      Philips AXIS gamma cameras. The effect on image quality of using half the
      acquisition time was also assessed. In the second part of the study, 50 sets of
      patient data were reprocessed by reconstructing half of the 360 degrees data to
      mimic a single-head 180 degrees acquisition. The 180 degrees images were then
      compared with 360 degrees images for the same patient using a visual score
      system. The effect of half-time 180 degrees data acquisition on quantification
      was also assessed using GE QuantiSPECT software. RESULTS: All phantom images from
      180 degrees acquisitions contained some degree of distortion at the periphery,
      but clearly retain the presence of centrally positioned caudate and putamen;
      hence 180 degrees acquisitions were deemed to produce clinically useful
      diagnostic images. The shorter (half) acquisition time leads to noisier but
      acceptable images for all configurations. In the patient study, there was
      complete agreement between the two reporters with no clinical difference in the
      diagnostic accuracy between the 180 degrees and 360 degrees images. However, 6 of
      50 180 degrees images were marked as poor quality but reportable, compared with 0
      of 50 in 360 degrees images. Quantification gave consistently lower nuclei to
      background ratio values for 180 degrees compared with 360 degrees for normal and
      abnormal patients. CONCLUSION: It is possible to obtain diagnostic DaTSCAN images
      using 180 degrees acquisition in difficult patients. The total length of the
      study may also be shortened by half using L-mode or V-mode camera head
      configuration.

PMID- 20032803
TI  - Performance of a 99mTc-labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate
      analogue in the detection of infections and tumours in mice: a comparison with
      [18F]FDG.
AB  - OBJECTIVE: The aim of this study was to investigate the differences in biological
      performance between a technetium-99m (Tc)-labelled glucose derivative, the Tc
      labelled 1-thio-beta-D-glucose 2,3,4,6-tetra-acetate analogue (Tc-TG) with F
      fluoro-2-deoxy-glucose ([F]FDG). METHODS: Binding of both tracers was performed
      in vitro to viable tumour cells and bacteria. Both tracers were injected into
      mice for targeting Staphylococcus aureus thigh muscle infections and subcutaneous
      rat lymphoma (RMA) tumours by using scintigraphy, or by radioactivity counts in
      excised tissues to determine the biodistribution. RESULTS: In-vitro binding
      studies revealed that both tracers bind more effectively to tumour cells
      expressing the glucose transporter 1 rather than the glucose transporter 2, and
      this binding was specific for [F]FDG. Tc-TG shows the highest binding to bacteria
      and, in addition, gives the highest rate of accumulation in infected thigh
      muscles in mice. Both tracers were rapidly removed from the circulatory system
      through the kidneys, and the majority of the injected radioactivity accumulated
      in the urinary bladder. Two hours after the injection radioactivity accumulation
      in two high-energy-dependent organs, heart, and liver, increased. Within 15 min
      of the injections, Tc-TG visualized the site of S. aureus infection or the
      tumour. CONCLUSION: We conclude that the new tracer Tc-TG may have potential use
      as a SPECT agent for infection and tumour imaging.

PMID- 20032804
TI  - A simplified one-pot automated synthesis of [18F]FHBG for imaging reporter gene
      expression.
AB  - BACKGROUND: 9-(4-[F]fluoro-3-hydroxymethylbutyl) guanine ([F]FHBG) has been used
      as a reporter probe to image the expression of the herpes simplex virus type 1
      thymidine kinase (TK) reporter gene in living organisms with positron emission
      tomography (PET). However, the routine production of [F]FHBG presents many
      challenging laboratory requirements. AIM: To develop a simple one-pot fully
      automated synthesis procedure of [F]FHBG amenable for its routine use in reporter
      gene expression PET imaging studies. METHODS: A TRACERlab FXF-N synthesizer was
      substantially modified and adapted to the synthesis of [F]FHBG through the two
      step one-pot procedure. After the fluorination reaction of the tosylate precursor
      and the hydrolysis of the intermediate product in the same reaction vessel, the
      final product was purified by Sep-Pak cartridges instead of the high performance
      liquid chromatography system. RESULTS: The fully automated synthesis of [F]FHBG
      with Sep-Pak purification was performed within a short synthesis time. The decay
      uncorrected radiochemical yield of [F]FHBG was 8-14% (n=10), the radiochemical
      purity was more than 99%, and the entire synthesis time was less than 40 min. In
      addition, the PET image of theTK-transfected nude mice model indicated a much
      higher uptake of [F]FHBG in the TK-transfected tumor region than in the control
      tumor region. CONCLUSION: The automated synthesis of [F]FHBG is very easy to
      carry out using one-pot reactions combined with Sep-Pak purification. The
      synthetic [F]FHBG can be used for PET imaging and monitoring of in vivo herpes
      simplex virus type 1 TK gene expression.

PMID- 20032805
TI  - Lack of predictive value of tachypnea in the diagnosis of pneumonia in children.
AB  - BACKGROUND: The World Health Organization (WHO) recommends the use of tachypnea
      as a proxy to the diagnosis of pneumonia in resource poor settings. OBJECTIVE: To
      assess the relation between tachypnea and radiographic pneumonia among children
      evaluated in a pediatric emergency department (ED). METHODS: Prospective study of
      children less than 5 years of age undergoing chest radiography (CXR) for possible
      pneumonia was conducted in an academic pediatric ED. Tachypnea was defined using
      3 different measurements: (1) mean triage respiratory rate (RR) by age group, (2)
      age-defined tachypnea based on WHO guidelines (<2 months [RR > or =60/min], 2 to
      12 months [RR > or =50], 1 to 5 years [RR > or =40]), and (3) physician-assessed
      tachypnea based on clinical impression assessed before CXR. The presence of
      pneumonia on CXR was determined by an attending radiologist. RESULTS: A total of
      1622 patients were studied, of whom, 235 (14.5%) had radiographic pneumonia. Mean
      triage RR among children with pneumonia (RR = 39/min) did not differ from
      children without pneumonia (RR = 38/min). Twenty percent of children with
      tachypnea as defined by WHO age-specific cut-points had pneumonia, compared with
      12% of children without tachypnea (P < 0.001). Seventeen percent of children who
      were assessed to be tachypneic by the treating physician had pneumonia, compared
      with 13% of children without tachypnea (P = 0.07). CONCLUSION: Among an ED
      population of children who have a CXR performed to assess for pneumonia, RR
      alone, and subjective clinical impression of tachypnea did not discriminate
      children with and without radiographic pneumonia. However, children with
      tachypnea as defined by WHO RR thresholds were more likely to have pneumonia than
      children without tachypnea.

PMID- 20032807
TI  - Kawasaki disease patients with redness or crust formation at the Bacille Calmette
      Guerin inoculation site.
AB  - BACKGROUND: A specific diagnostic test for Kawasaki disease (KD) is currently
      unavailable. Redness or crust formation at the Bacille Calmette-Guerin (BCG)
      inoculation site is listed as a positive sign in the diagnostic guidelines of KD.
      The purpose of this study was to investigate the epidemiologic features of KD
      patients with such changes at the BCG inoculation site and to evaluate the
      specificity of this sign in KD diagnosis. METHODS: Data on KD patients who
      received BCG vaccination were analyzed from a Japanese nationwide epidemiologic
      survey on KD conducted in 2007. Patients who had 5 or 6 principal signs (complete
      cases) with redness or crust formation at the BCG inoculation site were compared
      by sex, year of hospital visit, day of first hospital visit, recurrent status,
      and presence of KD in siblings. To evaluate the specificity of the sign for KD
      diagnosis, patients aged 2 years or younger who were diagnosed as having
      respiratory syncytial virus or rotavirus infection using a commercial rapid test
      and who required hospitalization were observed. RESULTS: Of the 15,524 KD
      patients with a history of BCG vaccination, 7745 (49.9%) had redness or crust
      formation at the BCG inoculation site. This was observed in more than 70% of
      complete KD patients aged 3 to 20 months. Of these patients, the proportion with
      this sign in the group whose first day of hospital visit was within 1 to 4 days
      from the onset was significantly larger than that of the other patients groups (5
      9 or 10+ days) (52.1%, P < 0.001). Among the patients with respiratory syncytial
      virus or rotavirus infection, none showed these changes at BCG inoculation site.
      CONCLUSIONS: Redness or crust formation at the BCG inoculation site is a useful
      diagnostic sign for KD among children aged 3 to 20 months in countries with a BCG
      vaccination program. Even if patients have 4 or fewer signs of the clinical
      criteria for KD, physicians should consider that patients with redness or crust
      formation at the BCG inoculation site could suffer from KD.

PMID- 20032806
TI  - Heart and skeletal muscle are targets of dengue virus infection.
AB  - BACKGROUND: Dengue fever is one of the most significant re-emerging tropical
      diseases, despite our expanding knowledge of the disease, viral tropism is still
      not known to target heart tissues or muscle. METHODS: A prospective pediatric
      clinical cohort of 102 dengue hemorrhagic fever patients from Colombia, South
      America, was followed for 1 year. Clinical diagnosis of myocarditis was routinely
      performed. Electrocardiograph and echocardiograph analysis were performed to
      confirm those cases. Immunohistochemistry for detection of dengue virus and
      inflammatory markers was performed on autopsied heart tissue. In vitro studies of
      human striated skeletal fibers (myotubes) infected with dengue virus were used as
      a model for myocyte infection. Measurements of intracellular Ca2+ concentration
      as well as immunodetection of dengue virus and inflammation markers in infected
      myotubes were performed. RESULTS: Eleven children with dengue hemorrhagic fever
      presented with symptoms of myocarditis. Widespread viral infection of the heart,
      myocardial endothelium, and cardiomyocytes, accompanied by inflammation was
      observed in 1 fatal case. Immunofluorescence confocal microscopy showed that
      myotubes were infected by dengue virus and had increased expression of the
      inflammatory genes and protein IP-10. The infected myotubes also had increases in
      intracellular Ca2+ concentration. CONCLUSIONS: Vigorous infection of heart
      tissues in vivo and striated skeletal cells in vitro are demonstrated.
      Derangements of Ca2+ storage in the infected cells may directly contribute to the
      presentation of myocarditis in pediatric patients.

PMID- 20032808
TI  - Rubella in Austria 2008-2009: no longer a typical childhood disease.
AB  - BACKGROUND: In February 2009, a cluster of rubella cases was recognized in
      Austria occurring between calendar weeks 3 and 7, 2009 after a long period of low
      rubella virus activity. A nationwide 2-dose measles, mumps, and rubella
      vaccination program had been introduced in 1994 to prevent this childhood
      illness. METHODS: An epidemiologic investigation was conducted to describe the
      cluster by time, place, and person. A confirmed outbreak case was defined as a
      febrile person (1) with generalized rash, which was laboratory confirmed or
      epidemiologically linked to a laboratory confirmed case and (2) who became ill
      after October 1, 2008 in the 2 affected provinces. A probable outbreak case was
      defined as any person meeting the clinical criteria of rubella and meeting the
      criterion 2 of a confirmed outbreak case. All cases were telephone interviewed on
      demographics and vaccination status. RESULTS: A total of 355 outbreak cases
      (including 247 confirmed cases) occurred in 2 neighboring Austrian provinces from
      mid-October 2008 until the end of June 2009, peaking in mid-March. The 2 most
      affected age groups were 15 to 19 (44.4%) and 20 to 24 year olds (32.4%). The
      vaccination status was available for 230 cases; 10% of cases had received 1
      measles, mumps, and rubella vaccine dose. No case had received 2 doses. Of the
      146 female cases, one laboratory-confirmed rubella infection in a pregnant 18
      year-old native Austrian resulted in elective abortion. CONCLUSIONS: These
      findings underline the waning epidemiologic role of children in maintaining the
      circulation of rubella virus and indicate that additional vaccination activities
      targeting >15 year olds are needed to achieve the 2010 WHO target for rubella
      elimination in the European Region.

PMID- 20032810
TI  - Profiling scoliosis in Rett syndrome.
AB  - To understand scoliosis, related comorbidities, and phenotype-genotype
      correlations in individuals with Rett syndrome (RTT), the Rare Disease Clinical
      Research Network database for RTT was probed. Clinical evaluations included a
      detailed history and physical examination, comprehensive anthropometric
      measurements, and two quantitative measures of clinical status, Clinical Severity
      Scale (CSS) and motor-behavioral analysis (MBA). All data were exported to the
      Data Technology Coordinating Center (DTCC) at the University of South Florida.
      Scoliosis assessment was based on direct examination and curvature measurements
      by radiography (Cobb angle). Statistical analyses included univariate and
      multiple logistic regression models, adjusting for age at enrollment or mutation
      type. Scoliosis data were available from 554 classic RTT participants, mean age =
      10 y (0-57 y). Scoliosis was noted in 292 (53%); mean age = 15 y with scoliosis
      and 6 y without. Using multiple regression analysis, MBA severity score, later
      acquisition, loss or absent walking, and constipation were associated with
      scoliosis. Two common methyl-CpG-binding protein 2 (MECP2) mutations, R294X and
      R306C, had reduced risk for scoliosis. These findings corroborated previous
      reports on scoliosis and extended understanding of comorbidities, clinical
      severity, and relative risk reduction for specific mutations. Clinical trial
      design should account for scoliosis and related factors judiciously.

PMID- 20032811
TI  - MT1G hypermethylation: a potential prognostic marker for hepatoblastoma.
AB  - Hepatoblastoma comprises only 1% of all cancers in childhood. Because of its low
      frequency, a small number of prognostic factors are described in hepatoblastoma
      and most of them are related to resectability. Microarray studies showed a large
      number of underexpressed genes in hepatoblastoma. Because aberrant DNA
      methylation has been recognized as an alternative mechanism for tumor suppressor
      gene inactivation, this could be involved with gene downregulation in these
      tumors. Despite the rarity of hepatoblastoma, this study evaluated the
      methylation pattern of 25 genes in 20 paraffin-embedded tumor specimens and five
      non-neoplastic liver samples (normal control) by quantitative methylation
      specific PCR (QMSP). The examination of the methylation profile of hepatoblastoma
      samples and normal liver specimens revealed a high tumor-specific DNA
      hypermethylation in the promoter regions of five genes (APC, CDH1, MT1G, RASSF1A,
      and SOCS1). Furthermore, MT1G hypermethylation showed a significant correlation
      with poor prognosis of patients with hepatoblastoma. This study represents the
      first quantitative evaluation of promoter hypermethylation in hepatoblastoma and
      demonstrated that aberrant methylation is a frequent event in this malignancy.
      Furthermore, our data provide evidence that MT1G hypermethylation may be useful
      as prognostic indicator for this disease and suggest that patients with
      hepatoblastoma may benefit from demethylating drug treatments.

PMID- 20032812
TI  - Fructose, but not dextrose, induces leukocyte adherence to the mesenteric venule
      of the rat by oxidative stress.
AB  - Recent evidence indicates that fructose is a pro-inflammatory molecule. Oral
      fructose induces serum and kidney inflammatory intercellular adhesion molecule-1
      (ICAM-1) in rats. Fructose also induces ICAM-1 expression in human aortic
      endothelial cells (HAEC) and monocyte chemoattractant protein-1 in proximal
      tubular renal cells. It is not known whether fructose may directly promote
      inflammation on the intestinal microcirculation. Accordingly, using intravital
      microscopy we studied the effect of topical fructose and dextrose on leukocyte
      adherence to the mesenteric venule of the rat. Leukocyte adherence was determined
      during a control period and after fructose was added to the mesentery, in the
      presence or absence of the NO donor spermine NONO-ate (SNO), and after i.v.
      injection of the antioxidant lipoic acid (LA). In separate experiments, we
      examined the effect of topical dextrose on leukocyte adherence to the mesenteric
      venule. Venular shear rate was calculated. Fructose, but not dextrose, induced
      significant inflammation independent of shear rate. This effect was completely
      blocked by SNO and LA, suggesting that fructose induces inflammation via reactive
      oxygen species (ROS) generation. These results suggest that fructose present in
      formulas may adversely affect the intestinal microcirculation of premature
      infants and potentially contribute to the pathogenesis of necrotizing
      enterocolitis (NEC).

PMID- 20032813
TI  - Biomarkers of epidermal innate immunity in premature and full-term infants.
AB  - Epidermal innate immunity is a complex process involving a balance of pro- and
      anti-inflammatory cytokines, structural proteins, and specific antigen presenting
      cells occurring against a background of neuroendocrine modulators such as
      cortisol. In this study, a multiplex array system was used to simultaneously
      determine multiple molecular factors critical for development of epidermal innate
      immune function from the skin surface of premature and term infants, healthy
      adults, and vernix caseosa. Samples were analyzed for Keratin 1,10,11, Keratin 6,
      involucrin, albumin, fibronectin and cortisol, and cytokines IL-1, TNFalpha, IL
      6, IL-8, MCP1, IP10, IFNgamma, and IL-1 receptor antagonist. Keratin 1,10,11 was
      decreased and involucrin was increased in infants versus adults. All infants had
      elevated IL1alpha and reduced TNFalpha versus adults. IL-6, IL-8, and MCP1 were
      significantly increased in premature versus term infants and adults. Skin surface
      cortisol and albumin were significantly elevated in premature infants. The
      biomarker profile in premature infants was unique with differences in structural
      proteins, albumin, and cytokines IL-6, IL-1beta, IL-8, and MCP1. The higher
      infant IL1alpha may be associated with skin barrier maturation. The significant
      elevations in skin surface cortisol for preterm infants may reflect a
      neuroendocrine response to the stress of premature birth.

PMID- 20032814
TI  - Altered cardiovascular rhythmicity in children with white coat and ambulatory
      hypertension.
AB  - Adults with ambulatory hypertension or white coat hypertension (WCH) display
      abnormal cardiovascular rhythms. We studied cardiovascular rhythms by Fourier
      analysis of 24-h ambulatory blood pressure (BP) measurement profiles in 129
      hypertensive children, 54 children with WCH, and 146 age-, height-, and gender
      matched healthy subjects. The day/night mean arterial pressure ratio was lower in
      hypertensive and patients with WCH compared with controls (1.13 versus 1.16
      versus 1.21, respectively; p < 0.0001). Eighty-five percent of controls were
      dippers compared with 74% of WCH (n.s.) and 64% of patients with ambulatory
      hypertension (p < 0.0001). The prevalence of 24-h rhythms was similar among the
      groups, but prevalence of 12-h BP rhythms was increased in hypertensive (67%) and
      WCH (72%) compared with controls (51%, p < 0.0001). The amplitudes of the 24-, 8
      , and 6-h BP rhythms were reduced in hypertensive and WCH compared with controls
      (p < 0.05). Hypertensive and patients with WCH displayed delayed 24-, 12-, 8-, 6
      h acrophases in comparison with controls (p < 0.05). In conclusion, hypertensive
      children exhibit abnormal cardiovascular rhythmicity compared with controls,
      especially a higher prevalence of nondipping compared with normotensive children.
      Abnormalities in patients with WCH are intermediate between healthy children and
      patients with ambulatory hypertension.

PMID- 20032809
TI  - Perinatal systemic inflammatory response syndrome and retinopathy of prematurity.
AB  - Fetal and neonatal inflammation is associated with several morbidities of
      prematurity. Its relationship to retinopathy of prematurity (ROP) has not been
      investigated. Our objective was to determine the relationship between cytokine
      levels and ROP in the first 3 postnatal wks. Data for this study were derived
      from the NICHD Cytokine Study. Dried blood spots (DBS) were obtained from infants
      <1000 g on days 0-1, 3 +/- 1, 7 +/- 2, 14 +/- 3, and 21 +/- 3. Infants were
      classified into three groups-no, mild, and severe ROP. Multiplex Luminex assay
      was used to quantify 20 cytokines. Temporal profiles of cytokines were evaluated
      using mixed-effects models after controlling for covariates. Of 1074 infants
      enrolled, 890 were examined for ROP and 877 included in the analysis. ROP was
      associated with several clinical characteristics on unadjusted analyses. Eight
      cytokines remained significantly different across ROP groups in adjusted
      analyses. IL-6 and IL-17 showed significant effects in early time periods (D0-3);
      TGF-beta, brain-derived neurotrophic factor (BDNF), and regulated on activation,
      normal T cell expressed and secreted (RANTES) in later time periods (D7-21) and
      IL-18, C-reactive protein (CRP), and neurotrophin-4 (NT-4) in both early and
      later time periods. We conclude that perinatal inflammation may be involved in
      the pathogenesis of ROP.

PMID- 20032816
TI  - The GSTP1 Ile105 Val polymorphism modifies the metabolism of toluene di
      isocyanate.
AB  - BACKGROUND: Toluene di-isocyanate (TDI) is widely used in the production of
      polyurethane foams and paints. As TDI causes respiratory disease in only a
      fraction of exposed workers, genetic factors may play a key role in disease
      susceptibility. Polymorphisms in TDI metabolising genes may affect elimination
      kinetics, resulting in differences in body retention, and in its turn differences
      in adverse effects. OBJECTIVES: To analyze how genotype modifies the associations
      between (i) TDI in air (2,4-TDI and 2,6-TDI) and its metabolites toluene diamine
      (TDA; 2,4-TDA and 2,6-TDA) in hydrolyzed urine; and (ii) 2,4-TDA and 2,6-TDA in
      hydrolyzed plasma and 2,4-TDA and 2,6-TDA in urine. METHODS: Workers exposed to
      TDI were analyzed for 2,4-TDI and 2,6-TDI in air (N=70), 2,4-TDA and 2,6-TDA in
      hydrolyzed urine (N=124) and in plasma (N=128), and genotype: CYP1A1*2A,
      CYP1A1*2B, GSTA1-52, GSTM1O, GSTM3B, GSTP1 I105V, GSTP1 A114V, GSTT1O, MPO-463,
      NAT1*3, *4, *10, *11, *14, *15, NAT2*5, *6, *7, and SULT1A1 R213H. RESULTS: GSTP1
      105 strongly modified the relationship between 2,4-TDA in plasma and in urine:
      ValVal carriers had about twice as steep regression slope than IleIle carriers. A
      similar pattern was found for 2,6-TDA. CYP1A1*2A, GSTM1, GSTP1, GSTT1, and MPO
      possibly influenced the relationship between TDA in plasma and urine. CONCLUSION:
      Our results show, for the first time, genetic modification on the human TDI
      metabolism. The findings suggest that GSTP1 genotype should be considered when
      evaluating biomarkers of TDI exposure in urine and plasma. Moreover, the results
      support earlier findings of GSTP1 105 Val as protective against TDI-related
      asthma.

PMID- 20032815
TI  - Association of birthweight and head circumference at birth to cognitive
      performance in 9- to 10-year-old children in South India: prospective birth
      cohort study.
AB  - To examine whether birthweight and head circumference at birth are associated
      with childhood cognitive ability in South India, cognitive function was assessed
      using three core tests from the Kaufman Assessment Battery for children and
      additional tests measuring long-term retrieval/storage, attention and
      concentration, and visuospatial and verbal abilities among 505 full-term born
      children (mean age 9.7 y). In multiple linear regression adjusted for age, sex,
      gestation, socioeconomic status, parent's education, maternal age, parity, body
      mass index, height, rural/urban residence, and time of testing, Atlantis score
      (learning ability/long-term storage and retrieval) rose by 0.1 SD per SD increase
      in newborn weight and head circumference, respectively (p < 0.05 for all), and
      Kohs' block design score (visuospatial ability) increased by 0.1 SD per SD
      increase in birthweight (p < 0.05). The associations were reduced after further
      adjustment for current head circumference. There were no associations of
      birthweight and/or head circumference with measures of short-term memory, fluid
      reasoning, verbal abilities, and attention and concentration. In conclusion,
      higher birthweight and larger head circumference at birth are associated with
      better childhood cognitive ability. The effect may be specific to learning, long
      term storage and retrieval, and visuospatial abilities, but this requires
      confirmation by further research.

PMID- 20032817
TI  - Interaction of maternal peroxisome proliferator-activated receptor gamma2
      Pro12Ala polymorphism with fetal sex affects maternal glycemic control during
      pregnancy.
AB  - It was suggested that fetal sex may substantially affect maternal glycemic
      control during pregnancy in genetically susceptible mothers. The peroxisome
      proliferator-activated receptor gamma2 (PPARgamma2) Pro12Ala polymorphism is
      known to affect glycemic control and may act in a sex-specific manner. This
      polymorphism is thus an attractive candidate to test this hypothesis using a
      second independent functionally relevant polymorphism. We analyzed the impact of
      fetal sex on maternal glycemic control during pregnancy in relation to the
      maternal PPARgamma2 Pro12Ala polymorphism. Two-thousand fourteen Caucasian women
      without preexisting diabetes and preexisting hypertension with singleton
      pregnancies delivering consecutively at the Charite obstetrics department were
      genotyped. Glycemic control was analyzed by measuring total glycated hemoglobin
      at birth. Correction for confounding factors and multiple testing was considered
      in the analysis. The maternal PPARgamma2 Pro12Ala polymorphism without
      consideration of fetal sex had no effect on blood pressure, new onset of
      proteinuria and total glycated hemoglobin at delivery. Mothers carrying both G
      alleles (GG genotype) delivering a girl had a higher (P = 0.015) total glycated
      hemoglobin (6.81 or - 0.50%) versus mothers carrying the same alleles but
      delivering boys (5.85 + or - 0.58%). Comparing mothers with the GG genotype
      delivering girls with mothers with CC or CG genotypes also delivering girls (6.32
      + or - 0.72%) revealed a significantly higher maternal total glycated hemoglobin
      at delivery in the former group (P < 0.009). Fetal sex/sex chromosomes may
      substantially affect maternal glycemic control in mothers who are carriers of the
      GG alleles of the PPARgamma2 Pro12Ala polymorphism.

PMID- 20032818
TI  - Development of a Pharmacogenetic Predictive Test in asthma: proof of concept.
AB  - OBJECTIVE: To assess the feasibility of developing a Combined Clinical and
      Pharmacogenetic Predictive Test, comprised of multiple single nucleotide
      polymorphisms (SNPs) that is associated with poor bronchodilator response (BDR).
      METHODS: We genotyped SNPs that tagged the whole genome of the parents and
      children in the Childhood Asthma Management Program (CAMP) and implemented an
      algorithm using a family-based association test that ranked SNPs by statistical
      power. The top eight SNPs that were associated with BDR comprised the
      Pharmacogenetic Predictive Test. The Clinical Predictive Test was comprised of
      baseline forced expiratory volume in 1 s (FEV1). We evaluated these predictive
      tests and a Combined Clinical and Pharmacogenetic Predictive Test in three
      distinct populations: the children of the CAMP trial and two additional clinical
      trial populations of asthma. Our outcome measure was poor BDR, defined as BDR of
      less than 20th percentile in each population. BDR was calculated as the percent
      difference between the prebronchodilator and postbronchodilator (two puffs of
      albuterol at 180 microg/puff) FEV1 value. To assess the predictive ability of the
      test, the corresponding area under the receiver operating characteristic curves
      (AUROCs) were calculated for each population. RESULTS: The AUROC values for the
      Clinical Predictive Test alone were not significantly different from 0.50, the
      AUROC of a random classifier. Our Combined Clinical and Pharmacogenetic
      Predictive Test comprised of genetic polymorphisms in addition to FEV1 predicted
      poor BDR with an AUROC of 0.65 in the CAMP children (n = 422) and 0.60 (n = 475)
      and 0.63 (n = 235) in the two independent populations. Both the Combined Clinical
      and Pharmacogenetic Predictive Test and the Pharmacogenetic Predictive Test were
      significantly more accurate than the Clinical Predictive Test (AUROC between 0.44
      and 0.55) in each of the populations. CONCLUSION: Our finding that genetic
      polymorphisms with a clinical trait are associated with BDR suggests that there
      is promise in using multiple genetic polymorphisms simultaneously to predict
      which asthmatics are likely to respond poorly to bronchodilators.

PMID- 20032819
TI  - Genetic variants in SLC9A9 are associated with measures of attention
      deficit/hyperactivity disorder symptoms in families.
AB  - OBJECTIVE: A family was previously identified that cosegregates a pericentric
      inversion, inv(3)(p14 : q21), with an early-onset developmental condition,
      characterized by impulsive behavior and intellectual deficit. The inversion
      breakpoints lie within DOCK3 and SLC9A9 at the p-arm and q-arm, respectively.
      Based on this report, these genes were selected to be evaluated in a family-based
      attention-deficit/hyperactivity disorder (AD/HD) association study. METHODS:
      Conners' Parent (CPRS) and Teacher (CTRS) Rating Scales of AD/HD symptoms and
      Conners' Continuous Performance Test (CPT) measures were collected and a minimal
      number of tagging single-nucleotide polymorphisms (SNPs) in each gene were
      selected for analysis. Analyses were performed on families who met research
      criteria for AD/HD. Using the program, QTDT, each tagging SNP was tested for
      association with T-scores from the Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition (DSM-IV) subscales according to the CTRS and CPRS, and
      five CPT measures. RESULTS: After adjusting for multiple testing, a SNP in the 3'
      UTR of SLC9A9, rs1046706, remained significantly associated (false discovery
      rate, q value <0.05) with scores on the DSM-IV hyperactive-impulsive and total
      symptom subscales according to the CTRS and errors of commission on the CPT. In
      addition, an intronic SLC9A9 SNP, rs2360867, remained significantly associated
      with errors of commission. CONCLUSION: Our results suggest that SLC9A9 may be
      related to hyperactive-impulsive symptoms in AD/HD and the disruption of SLC9A9
      may be responsible for the behavioral phenotype observed in the inversion family.
      The association with SLC9A9 is particularly interesting as it was recently
      implicated in a genome-wide association study for AD/HD. Further investigation of
      the role of SLC9A9 in AD/HD and other behavioral disorders is warranted.

PMID- 20032821
TI  - [Centennial of the French Society of Radiology and JFR 2009: past, present and
      future].

PMID- 20032820
TI  - Evidence for association of two variants of the nociceptin/orphanin FQ receptor
      gene OPRL1 with vulnerability to develop opiate addiction in Caucasians.
AB  - OBJECTIVES: The OPRL1 gene encodes the nociceptin/orphanin FQ receptor, which
      plays a role in regulating tolerance and behavioral responses to morphine.
      However, there is limited information on whether variants of OPRL1 are associated
      with vulnerability to develop opiate addiction. In this study, we examined five
      variants of OPRL1 and their role in determining vulnerability to develop opiate
      addiction. METHODS: We recruited 447 individuals: 271 former severe heroin
      addicts and 176 healthy controls. Using a 5'-fluorogenic exonuclease assay, we
      genotyped individuals at five variants in OPRL1. It was then determined whether
      there was a significant association of allele, genotype, or haplotype frequency
      with vulnerability to develop opiate addiction. RESULTS: When the cohort was
      stratified by ethnicity, we found that, in Caucasians but not in African
      Americans or Hispanics, the allele frequency of rs6090041 and rs6090043 were
      significantly associated point-wise with opiate addiction (P=0.03 and 0.04,
      respectively). Of the haplotypes formed by these two variants, one haplotype was
      found to be associated with protection from developing opiate addiction in both
      African-Americans (point-wise P=0.04) and Caucasians (point-wise P=0.04), and
      another haplotype with vulnerability to develop opiate addiction in Caucasians
      only (P=0.020). CONCLUSION: This study provides evidence for an association of
      two variants of the OPRL1 gene, rs6090041 and rs6090043, with vulnerability to
      develop opiate addiction, suggesting a role for nociceptin/orphanin FQ receptor
      in the development of opiate addiction.

PMID- 20032822
TI  - [Randomized vertebroplasty trials in the management of painful osteoporotic
      vertebral compression fractures].

PMID- 20032823
TI  - [Bone marrow edema: definition, diagnostic value and prognostic value].
AB  - Bone marrow edema is easily identified on MRI. The terminology suggests that the
      water content of bone marrow is increased when it is T1W hypointense and T2W
      hyperintense. It is a misnomer since, histologically, the abnormality does not
      correspond to marrow edema. The histological findings vary based on the
      underlying etiology and the presence of fibrosis or inflammatory infiltrate is
      frequent and often predominant. In France, this terminology is used routinely to
      describe such lesions. The term osteitis is preferred to describe these marrow
      signal changes in the setting of rheumatic joint diseases. The detection of bone
      marrow edema is important because of its diagnostic and prognostic value. It
      occurs in isolation and is reversible in patients with bone contusion and complex
      regional pain syndrome. It indicates underlying structural damage and may modify
      management in patients with rheumatoid arthritis or spondylarthropathies. MR
      scores for disease activity rely mainly on the presence of marrow edema. Finally,
      diffusion weighted MR allows quantification of marrow edema and could be more
      sensitive than conventional MRI to detect inflammation. The purpose of this
      article is to review the imaging features of marrow edema, review the underlying
      etiologies and its diagnostic and prognostic value.

PMID- 20032824
TI  - [Tomosynthesis: luxury or necessity?].
AB  - Digital mammography is replacing conventional film-screen mammography. One of its
      advantages is to offer options of advanced processing such as tomosynthesis.
      Tomosynthesis allows to avoid the overlap of tissues depitected on mammograms,
      and potentially to improve the detection of subtle lesion such as architectural
      distortion, permits the characterization of masses and of density asymmetry and
      the accurate measurement of beast lesion by a better delineation of the lesion
      borders. Furthermore, in cases of superimposition mimicking an abnormality, it
      can show the lack of a significant finding and decrease the recall rate. However,
      additional studies are necessary to evaluate its added valve by comparison to
      mammography in consecutive patients and not only in retrospectively selectioned
      cases and to define its indication in diagnostic and screening.

PMID- 20032825
TI  - [Sudden deafness: value of imaging. Results from a prospective study of 37
      patients].
AB  - PURPOSE: Review the CT and MR imaging findings in patients with sudden deafness
      (SD). PATIENTS AND METHODS: Thirty-seven patients with SD were prospectively
      included. All patients underwent MR evaluation of the brain and temporal bones to
      exclude classical etiologies such as vestibular schwannoma. CT of the temporal
      bones was also performed to exclude lesions of the bony labyrinth. A total of 100
      CT examinations of the temporal bone in control subjects were reviewed and
      measurements obtained to establish a reference standard to compare to findings in
      our patient population. RESULTS: Findings included: vestibular schwannoma in
      2.7%, labyrinthine hemorrhage in 8.1%, bony labyrinthine anomaly in 59.5%
      according to our criteria, and significantly more frequent than in our control
      subjects, including dehiscence of the superior semicircular canal in 8.1%,
      lateral semicircunal canal anomaly in 27% and vestibular anomaly in 16.2%.
      CONCLUSION: Some of the classical etiologies of SD were detected in our patient
      population, along with a high prevalence of size or morphological anomalies of
      the bony labyrinth, diagnosed in most cases from systematic measurements from CT
      images. In time, MRI should also allow detection of these abnormalities and
      diagnosis of lesions currently not detectable on MRI.

PMID- 20032826
TI  - [Evaluation of a fully integrated digital screening mammography program in the
      Vienne region].
AB  - PURPOSE: To evaluate a fully integrated digital screening mammography program
      (image acquisition, transfer and over-read). MATERIALS AND METHODS: between april
      2005 and December 2007, two imaging sites were authorized by the Department of
      Health to use digital mammography units (Senographe 2000D and 2000DS, GEMS) for
      screening mammography. the initial interpretation was made on a workstation with
      accompanying digital films. The images were also transmitted via the internet on
      the same day for over-read on a workstation. In addition, a <<classical>> over
      read was also performed from printed mammographic images using a viewbox.
      Differences in interpretation and BIRADS classification as well as economical
      considerations were analyzed between the types of interpretation setups. RESULTS:
      A total of 7008 screening mammograms were included. No significant problem was
      reported with regards to internet image transfers. No significant interpretation
      difference was noted related to the fully integrated digital imaging process.
      This technology could generate cost savings estimated in 2007 at 3.793/year
      (mailing fee). CONCLUSION: A fully integrated digital screening mammography
      program results in improved organisational processes and significant cost
      reductions without reduced diagnostic accuracy.

PMID- 20032827
TI  - [Evaluation of a computer aided detection system for lung nodules with ground
      glass opacity component on multidetector-row CT].
AB  - PURPOSE: To determine the performance of a CAD system for lung nodules with
      ground glass opacity component on multidetector-row CT. Materials and methods.
      The CT examinations of 17 patients with at least one persistent subsolid nodule
      were reviewed. A first non-blinded consensus review by two expert radiologists
      resulted in the detection of 104 subsolid nodules larger than 3 mm (74 nodules of
      ground glass attenuation and 30 mixed nodules with solid and ground glass
      components). The results from this review were used as a gold standard to
      determine the performances of the CAD system and 3 independent clinical
      radiologists involved with the primary interpretations. RESULTS: The sensitivity
      of the CAD system for the detection of ground glass opacities and mixed nodules
      was 53% and 73% respectively. These values were not statistically different from
      the values for the 3 independent observers (42-66% for ground glass opacities and
      63-80% for mixed nodules). The sensitivity of each observer significantly
      increased when the nodules detected by the CAD system were added to those
      detected by each observer (p<0.0001). CONCLUSION: A CAD system has a potential
      impact on the detection rate of subsolid nodules by radiologists.

PMID- 20032828
TI  - [Inflammatory myofibroblastic tumors of the lung: Imaging features].
AB  - Inflammatory myofibroblastic tumors are ubiquitous but most frequently affect the
      lung. The imaging features are non-specific but the diagnosis may be suggested in
      the presence of solitary pulmonary nodule or mass in children or young adults.
      The tumor may appear locally and regionally aggressive suggesting malignancy.
      Diagnostic confirmation is obtained from histological evaluation of the surgical
      specimen. Treatment is surgical with oncologic surgical resection.

PMID- 20032829
TI  - [Submandibular sialadenitis secondary to iodinated contrast injection].

PMID- 20032830
TI  - [Pelvic actinomycosis: CT and MR imaging features].

PMID- 20032831
TI  - [Reversible cerebrovascular event during an acute porphyric crisis. A case
      report].

PMID- 20032832
TI  - [Radiation myelopathy].

PMID- 20032833
TI  - [Answer to November e-quid. Ultrasound diagnosis of an omphalomesenteric fistula
      in an infant].

PMID- 20032835
TI  - [A new production system and a new presentation for the Journal].

PMID- 20032836
TI  - [COPD and distension: a simple inflation for respiratory physiologists?].

PMID- 20032837
TI  - [The "distal airways" series: from asthma to COPD].

PMID- 20032838
TI  - [A new series, "Diagnostic approach in thoracic pathology"].

PMID- 20032839
TI  - [Individualized treatment of metastatic non small cell lung carcinoma: a
      promising beginning].

PMID- 20032840
TI  - [PET-CT for evaluation of the solitary pulmonary nodule: an update].
AB  - INTRODUCTION: Positron emission tomography (PET) with 18F-FDG has become an
      important tool for the characterization of solitary pulmonary nodules (SPN).
      BACKGROUND: The results of the main meta-analyses show that the sensitivity and
      specificity of 18F-FDG PET for determining malignancy of SPN are close to 95% and
      80% respectively. The limits of the technology are now well known. False negative
      results are mainly due to certain histological types with low metabolic activity
      (such as bronchiolo-alveolar carcinoma and typical carcinoid), or small size
      (nodules less than 8 mm). False positives are mainly represented by granulomatous
      and infectious processes. VIEWPOINTS: A gain in accuracy occurred with the advent
      of hybrid PET/CT machines that combine the functional data from 18FDG-PET and the
      morphological data of computed tomography. Improved imaging protocols (eg.
      injection of iodinated contrast media) could further enhance the performance of
      PET-CT. Further improvements will rely on respiratory synchronization protocols
      and on the advent of new PET tracers. CONCLUSION: 18F-FDG PET-CT should be
      performed for any nodule over 8 mm in size when the pre-test probability of
      malignancy is not deemed negligible.

PMID- 20032841
TI  - [Prolonged exposure to atmospheric air pollution and mortality from respiratory
      causes].
AB  - Different designs can be used to analyze the relationships between respiratory
      mortality and long term exposure to atmospheric pollution: epidemiological
      studies (cohort, prevalence study) demonstrate the reality of the relationship
      and toxicological studies explain it. Cohort studies have the advantage of being
      able to take into account many confounding factors and thus avoid biases (which
      is not the case with prevalence studies), but require significant human and
      financial resources. They were first adopted in the US, but are now more often
      applied in Europe. The results are relatively consistent, as they all show a
      statistically significant association between an increase in particulate
      pollution and cardiopulmonary mortality. Mortality from lung cancer is also
      associated with long term exposition to particles and sometimes to ozone or
      nitrogen oxides. Cerebrovascular diseases and sudden death of young children have
      also been associated with particulate pollution. The relationships are more
      powerful for long term than short term exposure but are also linear and without
      threshold. In order to explain these effects (today the causality of the
      relationship is certain) there are many possible factors, particularly regarding
      particulate exposures: an increase in cardiovascular risk biomarkers (fibrinogen,
      white blood cells, and platelets), atherosclerosis, chronic inflammation of lung
      tissues increased by acute exposure, etc. More and more studies address the
      interaction between gene and environment and even epigenetic phenomena which
      could be responsible of these effects. Public Health impact could be quantified.
      The European E&H surveillance program Apheis, for example, estimated that if
      PM2.5 levels remained below 15 microg/m(3), a 30 year old person could see his
      life expectancy increased by 1 month to 2 years, depending on the studied city.
      Finally, mortality is not the only relevant indicator for health effects of air
      pollution. ISAAC studies address asthma, allergic rhinitis and eczema among
      children.

PMID- 20032842
TI  - [Effects of smoking on periodontal disease].
AB  - INTRODUCTION: Smoking is an independent risk factor for periodontal disease and
      tooth loss. STATE OF THE ART: Smoking impairs inflammatory and immune responses
      to periodontal pathogens, and exerts both systemic and local effects. Periodontal
      disease is increased both in prevalence and severity in smokers. Smoking is a
      predisposing factor to acute necrotizing ulcerative gingivitis and is associated
      with an increased rate of periodontal disease in terms of pocket formation and
      attachment loss, as well as alveolar bone loss. Cigar, pipe, water-pipe and
      cannabis smoking have similar adverse effects on periodontal health as cigarette
      smoking. Passive smoking is also an independent periodontal disease risk factor.
      Smokeless tobacco is associated with localized periodontal disease. Smokers
      respond less favourably to both non-surgical and surgical treatments and have
      higher failure rates and complications following dental implantation. Smoking
      cessation may halt the disease progression and improve the outcome of periodontal
      treatment. CONCLUSION: Smoking cessation counselling should be an integral part
      of periodontal therapy and prevention.

PMID- 20032843
TI  - [Endothelin receptor antagonists - their role in pulmonary medicine].
AB  - INTRODUCTION: There has been an explosion of interest in the biology of
      endothelin-1 in endothelium disease's physiopathology and in particular pulmonary
      arterial hypertension (PAH). This interest led up to the development of
      endothelin-receptor antagonists (ERA) drugs as major therapy for advanced PAH.
      STATE OF THE ART: Three active ERA drugs (bosentan, sitaxentan, ambrisentan) are
      nowadays approved for the treatment of PAH. Several randomised clinical trials
      have demonstrated their efficacy and safety in such domain. PERSPECTIVES AND
      CONCLUSION: Besides its vasoconstrictive effect, endothelin-1 (ET-1) plays a
      pivotal role on cell proliferation and apoptosis. ET-1 is a particularly
      interesting molecule linking idiopathic pulmonary fibrosis or systemic sclerosis,
      although preliminary results are still insufficient or controversial to conclude.
      CONCLUSION: The role of endothelin-1 in the pathogenesis of fibrosis and
      angiogenesis needs to be clarified and the interest of ERA in the diseases in
      which such injuries are preponderant might be demonstrated by further clinical
      trials.

PMID- 20032844
TI  - [First-line chemotherapy for metastatic non-small cell carcinoma: what are the
      options].
AB  - Until recently, first-line chemotherapy for advanced non-small cell lung cancer
      (NSCLC) was based on ASCO guidelines. Since several years, first-line
      chemotherapy is a platin-based doublet for patients with a good performans
      status. For elderly or unfit patients, a single-drug chemotherapy or a
      combination without cisplatin was recommended. The association of an anti
      angiogenic therapy, bevacizumab, with carboplatin-paclitaxel or cisplatin
      gemcitabine regimens improves progression-free survival for patients with non
      epidermoid tumors. The combination of cisplatin and pemetrexed is better in terms
      of survival than cisplatine-gemcitabine in these tumors. The choice of treatment
      according to histology is becoming a new concept. Another is maintenance therapy.
      The main objective is to reduce duration of platin-based chemotherapy while
      improving quality of life and progression-free survival. This concept is ongoing
      validation. The combination of cetuximab with platin-chemotherapy improves
      survival for all histologic types. We should integrate this new approach among
      other available treatments. First-line therapy for advanced NSCLC is changing. In
      the future, first-line therapy will be chosen according to clinical features and
      biomarkers such as gene mutations of EGFR.

PMID- 20032845
TI  - [Towards a histologically guided management for NSCLC].
AB  - Currently the management of non-small cell lung cancer with first line
      chemotherapy is dependent on the histology. The growth of morbid anatomy
      laboratories and molecular biology, alongside the rapid expansion of new
      therapies, is necessary for the selection of patients according to predictive
      criteria of efficacy and tolerance, allowing definition of a made to measure
      treatment.

PMID- 20032846
TI  - [Chest physiotherapy techniques - can they reduce hyperinflation].
AB  - The authors review the literature concerning the possibilities of modifying the
      mechanical characteristics of the respiratory system with breathing retraining
      and other chest physiotherapy intervention. Breathing retraining techniques with
      prolonged and active expiration induce increased work of breathing and do not
      help diaphragmatic function. Only pursed lips breathing seems to produce some
      mechanical advantages. The seated and forward position with fixed arms may reduce
      dyspnea but this does not appear to be caused by a decrease in operating lung
      volumes. By contrast, the dorsal decubitus position may reduce hyperinflation,
      giving some mechanical advantage to the diaphragm but does not reduce dyspnea and
      is not a position spontaneously adopted by patients. General muscular training
      may reduce ventilatory demand, and by reducing respiratory frequency lead to a
      decrease in the end expiratory lung volume; therefore inducing improvement in
      exercise tolerance.

PMID- 20032847
TI  - [Bronchoscopic treatment of emphysema].
AB  - In late stage chronic obstructive pulmonary disease, emphysema can worsen
      respiratory symptoms not only via the loss of surface for gas exchange but also
      via alterations in mechanical properties of the respiratory system (dynamic and
      static hyper-inflation). Emphysematous lung volume reduction aims at improving
      respiratory mechanics and symptomatology in patients with advanced emphysema.
      Lung volume reduction surgery (LVRS) has been shown to be effective in selected
      patient populations but its morbidity and costs are quite elevated. Alternatives
      to LVRS do not remove emphysematous lung tissue per say but rather consist of
      devices aiming to: 1) reduce the volume that affected lung parenchyma occupies
      (unidirectional endobronchial valves or plugs, parenchymal injection of bioactive
      scarring agents); 2) redistribute ventilatory flow (airway bypass systems).
      Preliminary studies of these devices have shown that they are relatively safe.
      These also show modest benefit in exercise capacity, although individual subjects
      can experience spectacular improvement. Current objective is to identify
      predictors of response to therapy with such devices.

PMID- 20032848
TI  - [Why and how to measure and optimize lung deposition of inhaled drugs].
AB  - The in vitro assessment of the aerosol fine particle 'respirable' fraction and
      the aerodynamic particle size distribution on cascade impactors is necessary to
      meet the demands of regulatory authorities but does not predict lung deposition
      of an inhaled drug notably in patients with chronic obstructive airway diseases.
      Total drug delivery to the lung can be assessed using pharmacokinetic methods.
      Pharmacokinetic studies are easier to conduct in patients with chronic
      obstructive diseases than imaging studies using two- or three-dimensional
      scintigraphic methods. For fast acting inhaled drugs, such as bronchodilators,
      the relationship between lung deposition and clinical efficacy can be established
      by modeling of the pharmacokinetic - pharmacodynamic (bronchodilation)
      relationship. Improvement of lung deposition is usually associated with a
      reduction of the dose required for clinical efficacy but the change in the dose
      response relationship is not proportionally related to the increase in lung
      deposition. Aerosols delivering small particles improve lung deposition, by
      distributing drug diffusely throughout the lungs, in particular by reaching
      peripheral airways. These aerosols do not improve clinical efficacy as evaluated
      on classical spirometric or clinical criteria but often permit a reduction in
      dosage. Also, they can minimize oropharyngeal deposition, reduce variability in
      lung deposition and spirometric response related to change in inspiratory flows.

PMID- 20032849
TI  - [Pulmonary neuroendocrine tumors].

PMID- 20032850
TI  - [Pulmonologists and children respiratory diseases].

PMID- 20032852
TI  - [Asthma in children: obesity, an emerging risk factor].

PMID- 20032851
TI  - [Progress in virology: impact on physiopathology of asthma in children].

PMID- 20032853
TI  - [Respiratory function tests in children].

PMID- 20032854
TI  - [Thoracic imaging in pediatrics: choosing the right test and controlling
      radiation].

PMID- 20032855
TI  - [Why focus on sleep in children?].

PMID- 20032856
TI  - [Management of pneumonia and pleuropneumonia in children].

PMID- 20032857
TI  - [Specific clinical manifestations of pulmonary vascular diseases].

PMID- 20032858
TI  - [Pulmonary hypertension in interstitial pneumopathies].

PMID- 20032859
TI  - [Chronic cor pulmonale in COPD].

PMID- 20032860
TI  - New cucurbitane triterpenoids and steroidal glycoside from Momordica charantia.
AB  - Three new cucurbitane triterpenoids 1-3 and one new steroidal glycoside 4, were
      isolated together with ten known compounds from Momordica charantia. The
      structures of new compounds were determined to be 19(R)-n-butanoxy-5 beta,19
      epoxycucurbita-6,23-diene-3beta,25-diol 3-O-beta-glucopyranoside (1), 23-O-beta
      allopyranosylecucurbita-5,24-dien-7 alpha,3beta,22(R),23(S)-tetraol 3-O-beta
      allopyranoside. (2), 23(R),24(S),25-trihydroxycucurbit-5-ene 3-O-{[beta
      glucopyranosyl(1-->6)]-O-beta-glucopyranosyl}-25-O-beta-glucopyranoside (3), and
      24(R)-stigmastan-3beta,5 alpha,6 beta-triol-25-ene 3-O-beta-glucopyranoside (4),
      respectively. Their structures were elucidated by the combination of mass
      spectrometry (MS), one and two-dimensional NMR experiments and chemical
      reactions.

PMID- 20032861
TI  - Molecular iodine-mediated cyclization of tethered heteroatom-containing alkenyl
      or alkynyl systems.
AB  - Molecular iodine has established itself as a readily available and easy-to-handle
      electrophilic and oxidizing reagent used in various organic transformations. In
      this review attention is focused on the use of molecular iodine in promoting
      cyclization (iodocyclization and cyclodehydroiodination) of tethered heteroatom
      containing alkenyl or alkynyl systems.

PMID- 20032862
TI  - Synthesis and study of novel coumarin derivatives potentially utilizable as
      memory media.
AB  - Novel coumarin derivatives, 2-oxo-2H-chromenecarbaldehyde hydrazones were
      prepared by reaction of substituted 2-oxo-2H-chromenecarbaldehydes with N
      aminoimides in ethanol in the presence of 4-toluenesulfonic acid as catalyst. The
      photochromic and thermochromic properties of the prepared compounds were
      investigated.

PMID- 20032863
TI  - Regioselective synthesis of new 2-(E)-cyano(thiazolidin-2-ylidene)thiazoles.
AB  - Cyclocondensation of 2-[bis(methylthio)methylene]malononitrile (1) and cysteamine
      (2) afforded 2-(thiazolidin-2-ylidene)malononitrile (3). This compound on
      treatment with NaSH gave the corresponding thioamide derivative 4a in a
      regioselective manner on the basis of its single crystal X-ray diffraction
      analysis. Reaction of this compound with several alpha-bromocarbonyl compounds
      gave new 2-(E)-cyano(thiazolidin-2-ylidene)thiazoles 5a-g.

PMID- 20032864
TI  - A facile synthesis of 2,4-disubstituted thiazoles using MnO2.
AB  - Structurally diverse thiazoles with electron-donating and electron-withdrawing
      groups were conveniently synthesized through manganese dioxide (MnO(2)) oxidation
      of the corresponding thiazolines. The effect of substitution at the 2- and 4
      positions was investigated. The desired thiazoles with aryl or vinyl
      substitutions at the 2- or 4-position can be obtained in good to excellent
      yields.

PMID- 20032865
TI  - Synthesis, structural studies and antitumoral evaluation of C-6 alkyl and alkenyl
      side chain pyrimidine derivatives.
AB  - The synthetic route for introduction of fluorophenylalkyl (compounds 5, 7, 14 and
      15) and fluorophenylalkenyl (compounds 4E and 13) side chains at C-6 of the
      pyrimidine nucleus involved the lithiation of the pyrimidine derivatives 1, 2 and
      11 and subsequent nucleophilic addition or substitution reactions of the
      organolithium intermediate thus obtained with 2-fluorophenylacetone, 4
      fluoroacetophenone or ethyl 4-fluorobenzoate as electrophiles. The structures of
      novel compounds were confirmed by (1)H-, (19)F- and (13)C-NMR and MS. Compounds 8
      and 10 containing unsaturated fluorophenylalkyl side chains showed better
      inhibitory effect than their saturated fluorophenylalkylated pyrimidine
      counterparts 7 and 9. A conformational study based on NOE enhancements showed the
      importance of the double bond and substitution in the side chain for the
      conformational preferences in relation to inhibitory activity. Among all tested
      compounds, C-5 furyl (12) and phenyl (13 and 15) substituted pyrimidine
      derivatives showed significant cytostatic activities against all tested tumor
      cell lines.

PMID- 20032866
TI  - Selenium utilization strategy by microalgae.
AB  - The diversity of selenoproteins raises the question of why so many life forms
      require selenium. Selenoproteins are found in bacteria, archaea, and many
      eukaryotes. In photosynthetic microorganisms, the essential requirement for
      selenium has been reported in 33 species belonging to six phyla, although its
      biochemical significance is still unclear. According to genome databases, 20
      species are defined as selenoprotein-producing organisms, including five
      photosynthetic organisms. In a marine coccolithophorid, Emiliania huxleyi
      (Haptophyta), we recently found unique characteristics of selenium utilization
      and novel selenoproteins using (75)Se-tracer experiments. In E. huxleyi,
      selenite, not selenate, is the main substrate used and its uptake is driven by an
      ATP-dependent high-affinity, active transport system. Selenite is immediately
      metabolized to low-molecular mass compounds and partly converted to at least six
      selenoproteins, named EhSEP1-6. The most (EhSEP2) and second-most abundant
      selenoproteins (EhSEP1) are disulfide isomerase (PDI) homologous protein and
      thioredoxin reductase (TR) 1, respectively. Involvement of selenium in PDI is
      unique in this organism, while TR1 is also found in other organisms. In this
      review, we summarize physiological, biochemical, and molecular aspects of
      selenium utilization by microalgae and discuss their strategy of selenium
      utilization.

PMID- 20032868
TI  - Novel bisquaternary oximes--reactivation of acetylcholinesterase and
      butyrylcholinesterase inhibited by paraoxon.
AB  - Four novel bisquaternary aldoxime cholinesterase reactivators differing in their
      chemical structure were prepared. Afterwards, their biological activity was
      evaluated for their ability to reactivate acetylcholinesterase (AChE; EC 3.1.1.7)
      and butyrylcholinesterase (BuChE; EC 3.1.1.8) inhibited by paraoxon. Their
      reactivation activity was compared with standard reactivators--pralidoxime,
      obidoxime and HI-6--which are clinically used at present. As it resulted, none of
      the prepared compounds surpassed obidoxime, which is considered to be the most
      potent compound if used for reactivation of AChE inhibited by paraoxon. In case
      of BuChE reactivation, two compounds (K053 and K068) achieved similar results as
      obidoxime.

PMID- 20032869
TI  - Phenolic compound profiles in berry skins from nine red wine grape cultivars in
      northwest China.
AB  - Phenolic compound profiles were investigated by HPLC-MS in two consecutive years
      to assess genotypic variation in berry skins of nine red Vitis vinifera
      cultivars. The results showed that the types and levels of phenolic compounds
      greatly varied with cultivar. Common wine grape cultivars such as Syrah, Cabernet
      Sauvignon, Cabernet Gernischt and Merlot contained more types of anthocyanins,
      flavonols, flavan-3-ols, stilbenes and phenolic acids than Gamay, Yan73, Pinot
      Noir, Zinfandel and Muskat Rosovyi. Yan 73 and Pinot Noir had abundant
      anthocyanins, but only a few nonanthocyanin phenolic compounds. Gamay, Zinfandel
      and Muskat Rosovyi contained only a few anthocyanins and flavonols. For a grape
      cultivar, the ratio of one anthocyanin content to total anthocyanin content did
      not change greatly from one year to the next, unlike for non-anthocyanins.
      Cluster analysis showed that except for Syrah and Yan 73, the phenolic profiles
      in the tested grape cultivars had no significant year-to-year variations.

PMID- 20032870
TI  - Microwave multicomponent synthesis.
AB  - In the manner that very important research is often performed by
      multidisciplinary research teams, the applications of multicomponent reactions
      involving the combination of multiple starting materials with different
      functional groups leading to the higher efficiency and environmentally friendly
      construction of multifunctional/complex target molecules is growing in
      importance. This review will explore the advances and advantages in microwave
      multicomponent synthesis (MMS) that have been achieved over the last five years.

PMID- 20032867
TI  - Phospholipids: key players in apoptosis and immune regulation.
AB  - Phosphatidylserine (PS), a phospholipid predominantly found in the inner leaflet
      of eukaryotic cellular membranes, plays important roles in many biological
      processes. During apoptosis, the asymmetric distribution of phospholipids of the
      plasma membrane gets lost and PS is translocated to the outer leaflet of the
      plasma membrane. There, PS acts as one major "eat me" signal that ensures
      efficient recognition and uptake of apoptotic cells by phagocytes. PS recognition
      of activated phagocytes induces the secretion of anti-inflammatory cytokines like
      interleukin-10 and transforming grow factor-beta. Deficiencies in the clearance
      of apoptotic cells result in the occurrence of secondarily necrotic cells. The
      latter have lost the membrane integrity and release immune activating danger
      signals, which may induce inflammatory responses. Accumulation of dead cells
      containing nuclear autoantigens in sites of immune selection may provide survival
      signals for autoreactive B-cells. The production of antibodies against nuclear
      structures determines the initiation of chronic autoimmunity in systemic lupus
      erythematosus. Since PS on apoptotic cells is an important modulator of the
      immune response, natural occurring ligands for PS like annexinA5 have profound
      effects on immune responses against dead and dying cells, including tumour cells.
      In this review we will focus on the role of PS exposure in the clearance process
      of dead cells and its implications in clinical situations where apoptosis plays a
      relevant role, like in cancer, chronic autoimmunity, and infections. Relevance of
      other phospholipids during the apoptosis process is also discussed.

PMID- 20032871
TI  - Synthesis and phytotoxic activity of new pyridones derived from 4-hydroxy-6
      methylpyridin-2(1H)-one.
AB  - Commercial dehydroacetic acid was converted into 4-hydroxy-6-methylpyridin-2(1H)
      one (3), which was then condensed with several aliphatic aldehydes to produce
      seven new title compounds in variable yields (35-92%). Reaction of 3 with
      alpha,beta-unsaturated aldehydes resulted in the formation of condensed pyran
      derivatives 4g' and 4h'. A mechanism is proposed to explain the formation of such
      compounds. The effects of all methylpyridin-2(1H)-one derivatives on the
      development of the dicotyledonous species Ipomoea grandifolia and Cucumis sativus
      and the monocotyledonous species Sorghum bicolor were evaluated. At the dose of
      6.7 x 10(-8) mol a.i./g substrate the compounds showed some phytotoxic
      selectivity, being more active against the dicotyledonous species. These
      compounds can be used as lead structures for the development of more active
      phytotoxic products.

PMID- 20032873
TI  - 18-Crown-6 and dibenzo-18-crown-6 assisted extraction of cesium from water into
      room temperature ionic liquids and its correlation with stability constants for
      cesium complexes.
AB  - The pH-profiles of the extraction of Cs(+) into four conventional (1-butyl-3
      methylimidazolium hexafluorophosphate and bis[trifluoromethyl)sulphonyl]imides of
      1-butyl-3-methylimidazolium, 1-hexyl-3-methylimidazolium, and 1-(2-ethylhexyl)-3-
      methylimidazolium) and two novel (trioctylmethylammonium salicylate and
      tetrahexylammonium dihexylsulfosuccinate) room temperature ionic liquids have
      been determined both in the absence and in the presence of crown ether (18-crown
      6 or dibenzo-18-crown-6). The pH-profiles of distribution ratio of crown ethers
      have been established in the same conditions. The relationship of cesium
      extraction efficiency both with the stability of its complexes with crown ethers
      and crown ethers' distribution ratio has been clarified.

PMID- 20032872
TI  - Hepatoprotective potential of extracts from seeds of Areca catechu and nutgalls
      of Quercus infectoria.
AB  - Aqueous extracts from seeds of Areca catechu L. (Arecaceae) (AC) and nutgalls of
      Quercus infectoria Oliv. (Fagaceae) (QI) were investigated for their
      hepatoprotective potential by studying their antioxidant capacity using four
      different methods, by determining their in vitro anti-inflammatory activity
      against 5-lipoxygenase, and by evaluating their hepatoprotective potential
      against liver injury induced by carbon tetrachloride (CCl(4)) in rats. AC and QI
      extracts exhibited potent antioxidant and anti-inflammatory activities. Treatment
      of rats with AC and QI extracts reversed oxidative damage in hepatic tissues
      induced by CCl(4). It is suggested that extracts rich in either condensed or
      hydrolysable tannins and known for their potent antioxidant and anti-inflammatory
      activities, may potentially confer protection against oxidative stress-induced
      liver injury. These data should contribute to evidence-based traditional
      medicines for anti-inflammatory and hepatoprotective effects of both extracts.

PMID- 20032874
TI  - Effects of alpha-melanocortin enantiomers on acetaminophen-induced hepatotoxicity
      in CBA mice.
AB  - Proteins and peptides in mammals are based exclusively on L-amino acids. Recent
      investigations show that D-amino acids exhibit physiological effects in vivo,
      despite of their very small quantities. We have investigated the hepatoprotective
      effects of the Land D-enantiomers of alpha-melanocortin peptide (alpha-MSH). The
      results showed that peptide-enantiomerism is related to the protective effects of
      melanocortin peptides in vivo. L-alpha-MSH exhibited potent hepatoprotective
      effect in the experimental model of acetaminophen induced hepatotoxicity in male
      CBA mice, while its D-mirror image was inefficient. Furthermore, the antibody to
      the L-peptide did not recognize the D-structure. The results indicate that the
      opposite peptide configuration may be used to modulate its function and
      metabolism in vivo and in vitro.

PMID- 20032875
TI  - Dissolution of microcrystalline cellulose in phosphoric acid--molecular changes
      and kinetics.
AB  - In this study, we aimed to dissolve microcrystalline cellulose (MCC) with
      phosphoric acid to obtain high-quality fermentable saccharides. MCC was directly
      dissolved in phosphoric acid (the concentration was 83%) for 10 hours at
      temperatures of 30, 50, and 70 degrees C. The structural changes of MCC were
      determined in detail with X-ray powder diffraction, solid-state cross
      polarization magic angle spinning (13)C-NMR, and X-ray photoelectron
      spectroscopy. The kinetics of MCC decrystallization during treatment with
      phosphoric acid was also compared at 30, 50, and 70 degrees C. With the
      assumption of first order kinetics, the Arrhenius parameters of K, A(0) and E(a)
      were calculated. The rate constants of decrystallization reaction (K) were 0.06,
      0.17, and 0.12 h(-1) respectively. The pre-exponential factor (A(0)) was 1.2 x
      10(6) h(-1), and the activation energy (E(a)) was 42.4 kJ/mol.

PMID- 20032876
TI  - Synthesis and antitumor activities of phenanthrene-based alkaloids.
AB  - A series of phenanthrene-based tylophorine derivatives (PBTs) were synthesized
      and their cytotoxic activities against the H460 human large-cell lung carcinoma
      cell line were evaluated. Among these compounds, N-(3-hydroxy-2,6,7-tri
      methoxyphenanthr-9-ylmethyl)-L-prolinol (5a), and N-(3-hydroxy-2,6,7-trimethoxy
      phenanthr-9-ylmethyl)-L-valinol (9) exhibited good activities, with IC(50) values
      of 11.6 and 6.1 microM, respectively.

PMID- 20032878
TI  - Antimalarial activity of ultra-short peptides.
AB  - Ultra-short peptides 1-9 were designed and synthesized with phenylalanine,
      ornithine and proline amino acid residues and their effect on antimalarial
      activity was analyzed. On the basis of the IC(50) data for these compounds, the
      effects of nature, polarity, and amino acid sequence on Plasmodium berghei
      schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4) and Lys
      Phe-Phe-Orn (5) showed a very important activity with IC(50) values of 3.31 and
      2.57 microM, respectively. These two tetrapeptides are candidates for subsequent
      in vivo assays and SARS investigations.

PMID- 20032879
TI  - Calpain inhibition reduces axolemmal leakage in traumatic axonal injury.
AB  - Calcium-induced, calpain-mediated proteolysis (CMSP) has recently been implicated
      to the pathogenesis of diffuse (traumatic) axonal injury (TAI). Some studies
      suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP)
      alterations observed in TAI. Seeking direct evidence for this premise we
      investigated whether subaxolemmal CMSP may contribute to axolemmal permeability
      alterations (APA) and pre-injury calpain-inhibition could reduce AP in a rat
      model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons
      with APA) was administered one hour prior to injury into the lateral ventricle;
      30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a
      calpain inhibitor) or its vehicle was applied in Wistar rats exposed to impact
      acceleration brain injury. Histological detection of traumatically injured axonal
      segments accumulating HRP and statistical analysis revealed that pre-injury
      administration of the calpain inhibitor MDL-28170 significantly reduced the
      average length of HRP-labeled axonal segments. The axono-protective effect of pre
      injury calpain inhibition recently demonstrated with classical
      immunohistochemical markers of TAI was further corroborated in this experiment;
      significant reduction of the length of labeled axons in the drug-treated rats
      implicate CMSP in the progression of altered AP in TAI.

PMID- 20032880
TI  - Synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives from amino
      acids.
AB  - A versatile method for the synthesis of chiral 1,4-disubstituted-1,2,3-triazole
      derivatives starting from easily accessible naturally occurring D-or L-amino
      acids as chiral synthons is described. The amino acids were converted into azido
      alcohols, followed by copper catalyzed [3+2] cycloaddition reactions between the
      azido alcohols and methyl propiolate and subsequent ester aminolysis with primary
      and secondary amines furnished the target compounds, which were obtained in
      excellent yields with no racemization. Docking of selected target compounds shows
      that the chiral 1,4-disubstituted-1,2,3-triazoles derivatives has the potential
      of mimicking the binding mode of known purine analogues.

PMID- 20032882
TI  - A new 2-(2-phenylethyl)chromone from Chinese eaglewood.
AB  - A new 2-(2-phenylethyl)chromone, 5,6,7,8-tetrahydroxy-2-(3-hydroxy-4
      methoxyphenethyl)-5,6,7,8-tetrahydro-4H-chromen-4-one (1) was isolated from the
      Chinese eaglewood [Aquilaria sinensis (Lour.) Gilg]. Its structure was
      established by detailed MS and NMR spectroscopic analysis, as well as comparison
      with literature data.

PMID- 20032881
TI  - The chemical composition and biological properties of coconut (Cocos nucifera L.)
      water.
AB  - Coconut water (coconut liquid endosperm), with its many applications, is one of
      the world's most versatile natural product. This refreshing beverage is consumed
      worldwide as it is nutritious and beneficial for health. There is increasing
      scientific evidence that supports the role of coconut water in health and
      medicinal applications. Coconut water is traditionally used as a growth
      supplement in plant tissue culture/micropropagation. The wide applications of
      coconut water can be justified by its unique chemical composition of sugars,
      vitamins, minerals, amino acids and phytohormones. This review attempts to
      summarise and evaluate the chemical composition and biological properties of
      coconut water.

PMID- 20032877
TI  - Neuroprotection by radical avoidance: search for suitable agents.
AB  - Neurodegeneration is frequently associated with damage by free radicals. However,
      increases in reactive oxygen and nitrogen species, which may ultimately lead to
      neuronal cell death, do not necessarily reflect its primary cause, but can be a
      consequence of otherwise induced cellular dysfunction. Detrimental processes
      which promote free radical formation are initiated, e.g., by disturbances in
      calcium homeostasis, mitochondrial malfunction, and an age-related decline in the
      circadian oscillator system. Free radicals generated at high rates under
      pathophysiological conditions are insufficiently detoxified by scavengers.
      Interventions at the primary causes of dysfunction, which avoid secondary rises
      in radical formation, may be more efficient. The aim of such approaches should be
      to prevent calcium overload, to reduce mitochondrial electron dissipation, to
      support electron transport capacity, and to avoid circadian perturbations. L
      theanine and several amphiphilic nitrones are capable of counteracting
      excitotoxicity and/or mitochondrial radical formation. Resveratrol seems to
      promote mitochondrial biogenesis. Mitochondrial effects of leptin include
      attenuation of electron leakage. Melatonin combines all the requirements
      mentioned, additionally regulates anti- and pro-oxidant enzymes and is, with few
      exceptions, very well tolerated. In this review, the perspectives, problems and
      limits of drugs are compared which may be suitable for reducing the formation of
      free radicals.

PMID- 20032883
TI  - Highly efficient and reusable copper-catalyzed N-arylation of nitrogen-containing
      heterocycles with aryl halides.
AB  - CuO/AB was found to be a simple and efficient catalyst for the N-arylation of a
      variety of nitrogen-containing heterocycles, giving the products in excellent
      yields.

PMID- 20032884
TI  - Pore forming properties of cecropin-melittin hybrid peptide in a natural
      membrane.
AB  - The pore forming properties of synthetic cecropin-melittin hybrid peptide (Acetyl
      KWKLFKKIGAVLKVL-CONH(2); CM15) were investigated by using photoreceptor rod outer
      segments (OS) isolated from frog retinae obtained by using the whole-cell
      configuration of the patch-clamp technique. CM15 was applied (and removed) to
      (from) the OS in approximately 50 ms with a computer-controlled microperfusion
      system. Once the main OS endogenous conductance was blocked with light, the OS
      membrane resistance was >or=1 G Omega, allowing high resolution, low-noise
      recordings. Different to alamethicines, CM15 produced voltage-independent
      membrane permeabilisation, repetitive peptide application caused a progressive
      permeabilisation increase, and no single-channel events were detected at low
      peptide concentrations. Collectively, these results indicate a toroidal mechanism
      of pore formation by CM15.

PMID- 20032885
TI  - Synthesis and evaluation of in vitro biological activity of 4-substituted
      arylpiperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4
      azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione.
AB  - A series of twenty arylpiperazine derivatives of 1,7,8,9-tetrachloro-10,10
      dimethoxy-4-azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared.
      These derivatives were tested in vitro with the aim of identifying novel lead
      compounds active against emergent and re-emergent human and cattle infectious
      diseases (AIDS, hepatitis B and C, tuberculosis, bovine viral diarrhea). In
      particular, these compounds were evaluated in vitro against representatives of
      different virus classes, such as a HIV-1 (Retrovirus), a HBV (Hepadnavirus) and
      the single-stranded RNA(+) viruses Yellow fever virus (YFV) and Bovine viral
      diarrhea virus (BVDV), both belonging to the Flaviridae. Compounds 2c, 2g and 3d
      showed a modest activity against CVB-2. The molecular structures of the starting
      imide 1 and one of propyl-piperazine derivatives, 3b, have been determined by an
      X-ray crystallography study.

PMID- 20032887
TI  - A striking exception to the chelate model for acyclic diastereocontrol: efficient
      access to a versatile propargyl alcohol for chemical synthesis.
AB  - The four-step, asymmetric synthesis of a chiral propargyl alcohol 1 from (R)
      pantolactone is described. A key feature of the synthesis is a diastereoselective
      acetylide addition to a chiral alpha-alkoxy-aldehyde 7, in which unusual Felkin
      selectivity is observed, despite the potential for chelation control. Crystalline
      propargyl alcohol 1 is valuable for complex molecule synthesis, and is easy to
      prepare in multi-gram quantities and high diastereomeric purity.

PMID- 20032886
TI  - Synthesis and antimicrobial activity of some pyridinium salts.
AB  - Some substituted benzylidenehydrazinylpyridinium derivatives bearing benzyl,
      ethylphenyl and propylphenyl groups on the pyridinium nitrogen were synthesized
      and screened for possible antibacterial and antifungal activities against
      Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida
      albicans using the microdilution method. Antimicrobial test results indicated
      that compounds containing a 3-phenylpropyl chain displayed the highest
      antimicrobial activity against Staphylococcus aureus and the compound 3d was the
      most active in the series against all tested bacteria and fungi strains.

PMID- 20032888
TI  - Generation of 500-member library of 10-alkyl-2-R(1),3-R(2)-4,10
      dihydrobenzo[4,5]imidazo[1,2-alpha]pyrimidin-4-ones.
AB  - Representative benzimidazopyrimidinones were previously reported to be
      intercalating antitumor agents. In this work, we used 2-substituted 4,10
      dihydrobenzo [4,5]imidazo[1,2-alpha]pyrimidin-4-ones for their diversification by
      regioselective alkylation. Under the conditions established, the alkylation gave
      10-alkyl derivatives which permitted the parallel generation of a 500-member
      library of the title compounds.

PMID- 20032889
TI  - MALDI-TOF MS profiling of annonaceous acetogenins in Annona muricata products for
      human consumption.
AB  - Annonaceous acetogenins are proposed as environmental neurotoxicants consumed
      through medicinal and alimentary habits and responsible for atypical parkinsonian
      syndromes observed in tropical areas. Potential sources of exposure still have to
      be determined, as, to date, only a few batches of products for human consumption
      were searched for these compounds. To assess the presence of acetogenins, we
      propose a fast, sensitive and accurate method of screening, using MALDI-TOF MS,
      with minimal sample preparation. Development of the technique is discussed. Its
      application to leaves of herbal tea, pulp and bottled nectar of Annona muricata
      is presented.

PMID- 20032890
TI  - 1-Arylsulfonyl-2-(pyridylmethylsulfinyl) benzimidazoles as new proton pump
      inhibitor prodrugs.
AB  - New arylsulfonyl proton pump inhibitor (PPI) prodrug forms were synthesized.
      These prodrugs provided longer residence time of an effective PPI plasma
      concentration, resulting in better gastric acid inhibition.

PMID- 20032891
TI  - Chemical constituents from the stems of Diospyros maritima.
AB  - A new phenolic, bis(6-hydroxy-2,3,4-trimethoxylphen-1-yl)methane (1) and a new
      butanedioate, butylmethyl succinate (2), along with twenty-nine known compounds
      including one naphthoquinone derivative, two chromanones, eight benzenoids, one
      lignan, one tocopherol, and sixteen triterpenoids were isolated from the stems of
      Diospyros maritima. epi-Isoshinanolone (3) was isolated in pure form for the
      first time. In addition, 5,7-dihydroxy-2-methylchomanone (4) was isolated from a
      natural source for the first time. Their structures were established on the basis
      of spectroscopic data as well as direct comparison with authentic samples.

PMID- 20032892
TI  - Germacrene D, a common sesquiterpene in the genus Bursera (Burseraceae).
AB  - The volatile components of the leaves of five Bursera species, B. copallifera, B.
      exselsa, B. mirandae, B. ruticola and B. fagaroides var. purpusii were determined
      by gas chromatography-mass spectrometry (GC-MS). Germacrene D was one of the
      predominant components (15.1-56.2%) of all of these species. Germacrene D has
      also been found in other Bursera species and some species of Commiphora, the
      sister group of Bursera, suggesting that the production of germacrene D might be
      an ancient trait in the genus Bursera.

PMID- 20032893
TI  - Protecting-group-free synthesis of 2-deoxy-aza-sugars.
AB  - The protecting-group-free asymmetric synthesis of 1,2,4-trideoxy-1,4-imino-L
      xylitol is readily achieved in five steps from 2-deoxy-D-ribose and with an
      overall yield of 48%. Key in this synthesis is the application of our recently
      developed Vasella-reductive amination and carbamate annulation methodologies to
      the synthesis of 2-deoxy-aza-sugars. The carbamate annulation occurred with
      excellent yield and diastereoselectively (>20:1 d.r.), in favour of the 3,4-cis
      isomer.

PMID- 20032894
TI  - Molecular iodine--an expedient reagent for oxidative aromatization reactions of
      alpha,beta-unsaturated cyclic compounds.
AB  - Prompted by the scant attention paid by published literature reviews to the
      applications of molecular iodine in oxidative aromatization reactions, we decided
      to review methods developed to-date involving iodine as an oxidant to promote
      aromatization of alpha,beta-unsaturated cyclic compounds.

PMID- 20032895
TI  - A chalcone glycoside from the fruits of Sorbus commixta Hedl.
AB  - Sorbus commixta Hedl. (Rosaceae) has been traditionally used in oriental
      countries for the treatment of asthma and other bronchial disorders. In this
      study, a chalcone glycoside was isolated from the ethyl acetate extract of the
      fruits of this plant. The compound was identified as neosakuranin based on the
      spectroscopic analysis and comparison with literature data. This is the first
      report of isolation of neosakuranin from Sorbus commixta.

PMID- 20032896
TI  - Cytotoxic activity of curcumin towards CCRF-CEM leukemia cells and its effect on
      DNA damage.
AB  - The cytotoxic activity of curcumin towards CCRF-CEM human T-cell leukemia cells
      was measured by the MTT assay. Tumor cells were more sensitive to the cytotoxic
      activity of curcumin or curcumin-Cu (II)compared to normal cells, and the IC(50)
      of curcumin towards CCRF-CEM cells was 8.68 microM, and that of curcumin-Cu (II)
      was 8.14 microM. The cell cycle distribution of curcumin-treated CCRF-CEM cells
      was analyzed by flow cytometry. DNA damage induced by oxidants such as curcumin
      Cu (II) ions is considered as one of the main causes of cell inactivation.
      Therefore, we analyzed the effect of curcumin on DNA damage by agarose gel
      electrophoresis and atomic force microscopy (AFM). Gel electrophoresis analyses
      showed that curcumin or Cu (II) alone failed to cause DNA damage in pBR322
      plasmid DNA as compared with the normal plasmid. However, DNA plasmids were
      mostly damaged after treatment with curcumin of different concentrations in the
      presence of Cu (II). Two forms were observed by means of AFM: closed circular
      plasmids and linear plasmids. DNA damage induced by a combination of curcumin and
      Cu (II) was also found by agarose gel electrophoresis, which was applied as
      control method to verify the results obtained by AFM.

PMID- 20032897
TI  - Synthesis and biological evaluation of novel 1-alkyl-tryptophan analogs as
      potential antitumor agents.
AB  - To seek novel antitumor agents, we designed and synthesized new 1-tryptophan
      analogs based on tryptophan catabolism. 1-Alkyl-tryptophan analogues including 1
      ethyltryptophan (1-ET), 1-propyltryptophan (1-PT), 1-isopropyltryptophan (1
      isoPT) and 1-butyltryptophan (1-BT) were synthesized from tryptophan. We examined
      whether those compounds had the antiproliferative effects on SGC7901 and HeLa
      cells line by using MTT assay in vitro, respectively. Compared to tryptophan, all
      targeted compounds efficiently inhibited proliferation of two cancer cell lines
      at 2 mmol/L for 48 hours. Among these tryptophan analogs, 1-BT showed the most
      powerful cytotoxicity against SGC7901 and HeLa cells at 1 mmol/L and 2 mmol/L
      concentration. These data suggest that some specific tryptophan analogs could be
      developed as potential anti-neoplastic agents.

PMID- 20032898
TI  - Correlation between antioxidant activities and phenolic contents of radix
      Angelicae sinensis (Danggui).
AB  - Radix Angelicae Sinensisis (RAS) is one of the most popular traditional Chinese
      herbal medicines. In the present study, six RAS extracts (i.e., phenolic extract
      PE, petroleum ether extract PEE, ethyl acetate extract EAE, absolute ethanol
      extract AEE, 95% ethanol extract 95 EE, and water extract WE) were prepared and
      their antioxidant activities measured by DPPH (1,1-diphenyl-2-picrylhydrazyl
      radical), ABTS [2,2'-azino-bis(3- ethylbenzothiazoline-6-sulfonic acid diammonium
      salt)], Reducing power, *O(2-) and lipid peroxidation assays. In general, PE, PEE
      and EAE had relatively high antioxidant activity, followed by AEE with moderate
      activity, as compared with 95 EE and WE that had low activity. Their phenolic
      contents (including total phenolic, ferulic acid, caffeic acid, same as below)
      were then determined by HPLC or spectrophotometry. The sequence of phenolic
      contents was roughly identical with that of antioxidant activity. When the values
      of 1/IC(50) of various antioxidant assays were used to evaluate the level of
      antioxidant of the RAS extracts, (plot between 1/IC(50) values and phenolic
      contents), the correlation coefficient (R) ranged from 0.642 to 0.941, with an
      average value of 0.839. Significant positive correlations demonstrated that the
      antioxidant effects of RAS might generally be considered a result of the presence
      of the phenolic compounds, especially ferulic acid and caffeic acid.

PMID- 20032899
TI  - Role of phosphatidyl-serine in bone repair and its technological exploitation.
AB  - In the 1970s, morphological evidence collected by electron microscopy linked
      mineral deposition ("calcification" or "mineralization") in newly-forming bone to
      membrane-encapsulated particles of a diameter of approximately 100 nm (50-200 nm)
      that were called "matrix vesicles". As the characterisation of these vesicles
      progressed towards their biochemical composition, the role of lipids in the
      biomineralization process appeared to be crucial. In particular, a group of cell
      membrane phospholipids were identified as major players in the crystal formation
      process. Indeed, in the 1980s it became clear that phosphatidylserine, together
      with proteins of the annexin family, was among the most important molecules in
      binding calcium ions and that this phospholipid was involved in the regulation of
      the early stages of mineralization in vivo. During the same period of time, the
      number of surgical implantations of orthopaedic, dental and maxilo-facial devices
      requiring full integration with the treated bone prompted the study of new
      functionalization molecules able to establish a stable bonding with the mineral
      phase of the host tissue. In the late 1990 s studies started that aimed at
      exploiting the potential of calcium-binding phospholipids and, in particular, of
      the phosphatidylserine as functionalization molecules to improve the
      osteointegration of artificial implants. Later, papers have been published that
      show the potential of the phophatidylserine and phosphatidylserine-mimicking
      coating technology to promote calcification both in vitro and in vivo. The
      promising results support the future clinical application of these novel
      osteointegrative biomaterials.

PMID- 20032901
TI  - Drugs for some common eye disorders.

PMID- 20032900
TI  - New conjugated benzothiazole-N-oxides: synthesis and biological activity.
AB  - Eleven new 2-styrylbenzothiazole-N-oxides have been prepared by aldol - type
      condensation reactions between 2-methylbenzothiazole-N-oxide and para-substituted
      benzaldehydes. Compounds with cyclic amino substituents showed typical push-pull
      molecule properties. Four compounds were tested against various bacterial strains
      as well as the protozoan Euglena gracilis as model microorganisms. Unlike
      previously prepared analogous benzothiazolium salts, only weak activity was
      recorded.

PMID- 20032902
TI  - Are swimming or aerobic exercise better than conventional exercise in ankylosing
      spondylitis patients? A randomized controlled study.
AB  - AIM: The aim of the study was to compare the effects of conventional exercise
      (CE), swimming and walking on the pulmonary functions, aerobic capacity, quality
      of life, Bath indexes and psychological symptoms in patients with ankylosing
      spondylitis (AS). METHODS: Forty-five patients were randomised into either
      swimming (group 1), walking (group 2), CE group (group 3). Patients in Group 1
      performed CE and swimming, patients in Group 2 performed CE and walking and
      patients in Group 3 performed CE only. Exercise sessions were performed three
      times a week for a period of six weeks. Patients were assessed before and after
      the rehabilitation program, with respect to, pulmonary function test (forced
      vital capacity [FVC, mL], forced expiration volume in one second [FEV1, mL],
      FEV1/FVC (%) and vital capacity [VC, mL]), maximal oxygen uptake (pV.O2), 6
      minute walking test (6MWT), Bath Ankylosing Spondylitis Functional Index, Bath
      Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis
      Metrology Index, Nottingham Health Profile and Beck Depression Inventory.
      RESULTS: There were significant increases in pVO2 and 6MWT after treatment in
      Groups 1 and 2 (P<0.05). FeV1, FVC and VC improved significantly with treatment
      in all three groups (P<0.05). A statistically significant improvement was
      observed in energy, emotional reaction and physical mobility sub-scores of NHP in
      three exercise groups after completion of the exercise program (P<0.05).
      CONCLUSIONS: Swimming, walking and CE had beneficial effects on the quality of
      life and pulmonary functions. Aerobic exercises such as swimming and walking in
      addition to CE increased functional capacities of patients.

PMID- 20032903
TI  - The effect of different physical activity levels on muscle fiber size and type
      distribution of lumbar multifidus. A biopsy study on low back pain patient groups
      and healthy control subjects.
AB  - AIM: Previous studies examining the multifidus fiber characteristics among low
      back pain (LBP) patients have not considered the variable of physical activity.
      The present study sought to investigate the muscle fiber size and type
      distribution of the lumbar multifidus muscle among LBP patient groups with
      different physical activity levels and healthy controls. METHODS: Sixty-four
      patients were assigned to one of three groups named according to the physical
      activity level, determined for each patient by the International Physical
      Activity Questionnaire. These were low (LPA), medium (MPA) and high (HPA)
      physical activity groups. A control group comprising of 17 healthy individuals
      was also recruited. Muscle biopsy samples were obtained from the multifidus
      muscle at the level L4-L5. RESULTS: contrast with the control group, LBP patient
      groups showed a significantly higher Type II fiber distribution as well as
      reduced diameter in both fiber types (P<0.05). The physical activity level did
      not have an effect on multifidus characteristics since no significant differences
      were observed in fiber type and diameter (P>0.05) among LPA, MPA and HPA patient
      groups. Various pathological conditions were detected which were more pronounced
      in LBP groups compared to the control (P<0.05). Males had a larger fiber diameter
      compared to females for both fiber types (P<0.05). CONCLUSIONS: The results
      showed that the level of physical activity did not affect muscle fiber size and
      type distribution among LBP patients groups. These findings suggest that not only
      inactivity but also high physical activity levels can have an adverse effect on
      the multifidus muscle fiber characteristics.

PMID- 20032904
TI  - Evidences of memory dysfunction and maladaptive coping in chronic low back pain
      and rheumatoid arthritis patients: challenges for rehabilitation.
AB  - AIM: This study investigates whether chronic low back pain (LBP) and rheumatoid
      arthritis (RA) patients have deficits in memory functioning and whether there is
      correlation between memory scores and coping skills, as a disability evaluation
      measure. METHODS: We studied 2 samples of patients of both genders between 20 and
      70 years-old, in a cross-sectional design: 21 low back pain and 23 rheumatoid
      arthritis. Patients were compared to historical controls. Assessment of primary
      outcome included memory evaluation (Wechsler Memory Scale III) and measures of
      coping strategies (FABQ, CPCI, CSQ). Other data included depression (HAD), pain
      (VAS), work status, use of medications, and perceived memory complaints. Analysis
      were made of between-group differences. RESULTS: Both groups were comparable
      regarding demographic status, had high scores of memory complaint, and low
      performance in memory assessment when compared to normative data. Only LBP
      patient's measures of catastrophizing and coping were significantly correlated to
      late memory indices. No correlations were found between memory and Visual
      Analogue Scale (VAS) or pain chronicity in both groups. One may suggest that both
      chronic localized and widespread pain can imply in cognitive changes and be
      correlated to coping dysfunction. However, bias of existence of depression/
      anxiety and psychotropic medication cannot be excluded. CONCLUSIONS: Both groups
      of chronic pain patients are likely to have impaired memory. Maladaptive coping
      correlates to LBP, but not to RA. A further controlled protocol must include
      greater sample of patients. By analyzing memory deficits of chronic pain
      patients, clinicians could establish targeted rehabilitation programs and
      outcomes. Some techniques are discussed.

PMID- 20032905
TI  - Agreement of functional independence measure item scores in patients transferred
      from one rehabilitation setting to another.
AB  - AIM: Classification and payment systems that incorporate a functional measure
      used in routine clinical practice can only be as accurate as the underlying
      functional measure. The test-retest reliability in clinical practice of the
      individual item scores of the Functional Independence Measure (FIM), a functional
      measure used in classification and payment systems has been investigate. The aim
      of this study was to analyse paired measurements of FIM item scores carried out
      in routine clinical practice for patients transferred from one Rehabilitation
      Unit to another, and to determine the interrater reliability using standard
      measures of agreement and bias. METHODS: Patients who were transferred between
      two rehabilitation units between August 2006 and October 2007 had a FIM scored on
      discharge from the original unit and a FIM scored on admission to the second
      unit. A short time between score and re-score reduced the probability of
      significant functional change. A retrospective analysis was performed. RESULTS:
      Paired FIM item scores from143 patients were included in the review. Raw
      agreement between the two scores for each FIM item was low, with a mean of 54 +
      18 pairs (%) matching. The range of difference between scores was wide. Weighted
      kappa values were generally in the fair agreement range as were the intraclass
      correlation coefficients. Tests for bias and homogeneity showed that just over
      half of the items had significant differences in the two sets of scores. Weighted
      k showed only fair agreement for FIM items. Contributing factors for this could
      include incomplete FIM training of some staff, insufficient attention to accurate
      scoring, actual clinical changes, differences between patient performance in
      different settings, and variation in scoring because of the large number of staff
      involved in scoring the FIM in the multidisciplinary team within our settings.
      CONCLUSIONS: Caution needs to be exercised when utilizing the FIM individual item
      scores in clinical practice as part of clinical or funding classifications or in
      benchmarking as this study indicates only fair inter-rater reliability of these
      scores in clinical practice.

PMID- 20032906
TI  - Child rehabilitation refusal: why it happens and possible strategies to avoid it.
AB  - AIM: Despite an obvious need for rehabilitative treatment, some parents deny
      consent and some others withdraw their children from a previously accepted
      program. There is limited literature concerning how to prevent this, serving the
      child's best interest, and the existing is mainly focused on legal implications.
      METHODS: This was a naturalistic study, carried out using data obtained during
      the diagnostic evaluation of 166 children (all those seen in the Child
      Neuropsychiatry Unit). For 25 children (15.1%), parents refused or interrupted
      suggested treatment. RESULTS: Statistical analysis showed that there is a
      significant difference in terms of impairment in children of parents accepting or
      refusing the rehabilitative treatment. Treatment discontinuation is related to
      the diagnosis (higher percentage in severe language disorders or complex
      developmental disorders), higher reduction in global functioning, higher
      disability burden, need for integrated treatment, lower age. CONCLUSIONS:
      Findings of this study could be useful in order to better plan rehabilitative
      options and goals. It is possible that an attempt to increase parental
      involvement in the rehabilitative program could lead to a decrease in treatment
      discontinuation. Anyway, more research is needed because we are still far from
      having a good predictive model to anticipate and, if possible, avoid treatment
      discontinuation.

PMID- 20032907
TI  - A modified constraint-induced movement therapy (CIT) program improves paretic arm
      use and function in children with cerebral palsy.
AB  - AIM: Constraint-induced movement therapy (CIT) is a rehabilitation intervention
      put forward by Taub and colleagues for sensorimotor disorders in children with
      hemiparesis, comprising consisting of the restraint of the unaffected arm and
      concurrent intensive training of the affected arm for six hours/day for two
      weeks. The aim of this study was to evaluate the effectiveness of a modified CIT
      program (mCIT) characterized by restraining the unaffected hand with a cotton
      mitten during daily activities and a reduced intensity training program for two
      h/week for five weeks. METHODS: Ten children (age: 1-9 years) with hemiparetic
      cerebral palsy were enrolled in a randomized, cross-over study in which the
      effects of a mCIT and a conventional physiotherapy program were compared. The
      amount of use and the functional performance of the affected arm were evaluated
      by means of two specifically devised tests (Use and Function Test). A further
      test evaluated functional performance during bimanual tasks. These measures
      showed a good inter-rater and inter-session reliability. All tests were
      administered before, at the end and four weeks after treatment. RESULTS:
      Significant differences between the two therapeutic approaches were evidenced in
      both affected arm use (P=0.008) and function (P=0.018). These improvements
      maintained at the follow-up (Use Test P=0.07; paretic arm function P=0.012).
      Bimanual function performance showed a trend towards improvement in both post
      treatment and follow-up testing. The conventional physiotherapy group did not
      show any improvement in any outcome measure. CONCLUSIONS: The mCIT program
      proposed in the present study showed to be a promising rehabilitative procedure
      in children with congenital arm paresis after cerebral palsy.

PMID- 20032908
TI  - Long lasting benefits following the combination of static night upper extremity
      splinting with botulinum toxin A injections in cerebral palsy children.
AB  - AIM: Botulinum toxin A injections and orthotics have been used to manage upper
      extremity spasticity in hemiplegic children. The authors performed a study to
      evaluate the necessity and effectiveness of a static night splint following
      outpatient botulinum toxin A treatment in children with upper limb spastic
      cerebral palsy. METHODS: Twenty children with upper limb spastic cerebral palsy
      were treated with botulinum toxin A injections. A static night splint was applied
      in half of them. Objective assessment of upper limb function was performed at
      baseline, at 2 and 6 months after botulinum toxin A injection using the Quality
      of Upper Extremity Skills Test. RESULTS: After botulinum toxin A treatment, both
      groups showed an improvement on their previous functional level of the injected
      upper extremity. At 2 months, children in group A showed a 15.4% improvement,
      whereas children in group B improved by 12.2% from baseline; these were not
      statistically significant (P=0.326). At 6 months, group A still maintained a
      15.9% improvement in function compared to group B which differed only by 4.2%
      from prebotulinum toxin A baseline; these differences were statistically
      significant (P=0.000). Complications related to the botulinum toxin A injection
      were not observed. The static CONCLUSIONS: Static night splinting following
      botulinum toxin A injections has shown a definite treatment effect in reducing
      spasticity and improving function in children with upper limb spastic cerebral
      palsy.

PMID- 20032909
TI  - Evaluation of a Patient-Specific Index as an outcome measure for physiotherapy in
      Parkinson's disease.
AB  - AIM: The aim of this paper was to develop and evaluate a patient-specific index
      for physiotherapy in Parkinson's disease (PSI-PD). METHODS: In the PSI-PD,
      patients 1) select problematic activities out of a predefined list, with one self
      report item; 2) rank selected items in order of importance; and 3) rate severity
      for each ranked item. To examine test-retest reliability, a cohort of patients
      was asked to complete the PSI-PD twice. Afterwards, validity was evaluated using
      a telephone interview. RESULTS: The PSI-PD was completed twice by 81 patients.
      Test-retest agreement for the selection of activity limitations was 73% to 94%.
      Items ranked by patients were categorized into domains, of which gait, transfers
      and dexterity were rated most frequently (41%-70%). Test-retest agreement for
      ranked domains ranged from 74% to 82%. Interviews confirmed that the PSI-PD
      reliably identified problem areas. CONCLUSIONS: The PSI-PD is a relevant,
      reliable and valid instrument to identify limitations in everyday activities that
      are important for both PD patients and physiotherapists.

PMID- 20032910
TI  - The Italian version of the Mayo-Portland Adaptability Inventory-4. A new measure
      of brain injury outcome.
AB  - AIM: The assessment of major obstacles to community integration which may result
      from an acquired brain injury (ABI) is needed for rational planning and effective
      management of ABI patients' social adjustment. Currently, such a generally
      acceptable measure is not available for the Italian population. This paper
      reports the translation process, the internal consistency, and the inter-rater
      reliability data for the Italian version of the Mayo-Portland Adaptability
      Inventory-4 (MPAI-4), a useful measure with highly developed and well documented
      psychometric properties. The MPAI-4 is specifically designed to assess socially
      relevant aspects of physical status and cognitive-behavioural competence
      following ABI. It is a 29-item inventory which is divided into three subdomains
      (Abilities, Adjustment, and Participation indices) covering a reasonably
      representative range METHODS: Twenty ABI patients with at least one-year
      discharge from the rehabilitation facilities were submitted to the Italian MPAI
      4. They were independently rated by two different rehabilitation professionals
      and a family member/significant other serving as informant (SO). Internal
      consistency was assessed by calculating the Cronbach's alpha values. Inter-rater
      agreement for individual items was statistically examined by determining the
      interclass correlation coefficient (ICC). RESULTS: In addition to the 8% of
      perfectly correspondent sentences, a clear prevalence (75.5%) of minor semantic
      variations and formal variations with no semantic value at the sentence-to
      sentence matching was found. Full-scale Cronbach's alpha was 0.951 and 0.947 for
      the two professionals (rater #1 and rater #2, respectively), and was 0.957 for
      the family member serving as informant (rater #3). Full-Scale ICC (2.1) between
      professionals and SOs was 0.804 (CI=95%; lower-upper bound=0.688-0.901).
      CONCLUSIONS: The Italian MPAI-4 shares many psychometric features with the
      original English version, demonstrates both good internal consistency and good
      inter-rater reliability. The MPAI-4 confirms to be suitable for research
      applications in postacute settings as an efficient, broad and inclusive outcome
      measure for adult subjects with ABI.

PMID- 20032911
TI  - Reliability and validity of the Turkish version of the ECOS 16 questionnaire in
      postmenopausal osteoporosis.
AB  - AIM: The purpose of this study was to develop a Turkish version of ECOS 16
      Questionnaire and assess its reliability and validity. METHODS: Sixty four women
      with postmenopausal osteoporosis were included in the study. It was mandatory for
      all patients to be Turkish literate and without symptoms of dementia. Patients
      who were diagnosed as secondary osteoporosis by clinical and laboratory
      examinations were excluded from the study. After translation process, the Turkish
      version of the scale was applied to each participant twice with an interval of 2
      weeks. For reliability study, internal consistency (Chronbach alpha) of ECOS 16
      total score and test-retest intraclass correlation coefficient (ICC) were
      calculated. Validation study was assessed by correlating the scale with QUALEFFO
      41. RESULTS: The mean age at menopause and age of patients were 45.61+/-6.04
      years and 59.91+/-8.69 years respectively. Chronbach alpha of the Turkish version
      of the ECOS 16 was 0.90. The test-retest reliability (ICC) of the Turkish version
      of the ECOS 16 was determined as 0.83 for the total score, and ranged between
      0.72-0.88 for individual items. In terms of validity; the Turkish version of ECOS
      16 correlated significantly with QUALEFFO 41 (r=0.844 P<0.0001). CONCLUSIONS: .
      The Turkish version of the ECOS 16 is a reliable and valid questionnaire to be
      used in the evaluation of Turkish women with postmenopausal osteoporosis.

PMID- 20032912
TI  - Validation and reliability of the Turkish version of the fear avoidance beliefs
      questionnaire in patients with low back pain.
AB  - AIM: The aim of this study was to translate the questionnaire into Turkish and to
      investigate the test-retest reliability, construct validity and its sensitivity
      to change following physical therapy. METHODS: The questionnaire was translated
      into Turkish using the forward and backward translation technique. Test-retest
      reliability was assessed with the correlation coefficients. Scale analysis for
      internal validity, the Cronbach's alpha score was calculated. Construct validity
      was tested with principal components analysis and was also tested with divergent
      validity. Following three weeks of treatment, sensitivity to change and
      responsiveness of the questionnaire was assessed. RESULTS: The questionnaire was
      applied on 55 patients and high correlations were found on the repeated items 48
      hours later. In the scale analysis, the Cronbach's alpha score was found as 0.911
      for the total questionnaire. Two factors were found compatible with the original
      questionnaire with principal components analysis. These two factors explain
      61.647% of the total variance in the questionnaire performed on 150 patients. In
      divergent validity, the fear avoidance beliefs were found in low correlation with
      the clinical variables. Sensitivity to change and responsiveness of the FABQ was
      found to be low. CONCLUSIONS: FABQ has sufficient psychometric features for its
      applicability in the Turkish population with subacute and chronic low back pain.

PMID- 20032913
TI  - Spectral analysis of the human voice: a potentially useful tool in
      rehabilitation.
AB  - AIM: The study was aimed at providing normal data from the spectral analysis of
      the human voice. This step of the research has a bearing in the field of speech
      and language retraining. The possibility of providing quantitative data would
      hasten monitoring of possible improvements along a rehabilitation program.
      METHODS: A cross-sectional, observational design was applied. Thirty-two men, 30
      women and 34 children were the healthy volunteers participating to the study. The
      adult participants had to repeat the 12 words of the ENPA instrument for Italian
      language. The children repeated words from the Fanzago test. Real Time Pitch
      Model 5121 manufactured by Kay PENTAX recorded the voice. The following spectral
      descriptors were obtained for each word: mean frequency, standard deviation,
      loudness, duration, jitter and shimmer. Test-retest performance was also checked.
      RESULTS: As expected, women had a higher mean frequency than men (119+/-3 v.
      193+/-5 Hz), but the variation coefficient (CV: SD/mean) was the same, namely
      0.1. By contrast, children had a significantly higher mean frequency (245+/-35
      Hz) and a lower CV. Under this respect, groups could be statistically divided.
      Loudness was practically the same among the groups, whereas the children had
      short time duration in word uttering. Children had also the highest jitter
      values, whereas shimmer values were higher in men. CONCLUSIONS: Spectral analysis
      of the human voice is recommended in each laboratory of speech and language
      rehabilitation. The usual testing is not replaced but can exploit the accurate
      definition of voice descriptors.

PMID- 20032914
TI  - Good recovery from aphasia is also supported by right basal ganglia: a
      longitudinal controlled PET study. EJPRM-ESPRM 2008 award winner.
AB  - AIM: It has long been a matter of debate whether recovery from aphasia after left
      perisylvian lesion is mediated by perilesional left hemispheric regions or by
      right homologous areas. To investigate the neural substrates of aphasia recovery,
      a longitudinal study in patients after a left single perisylvian stroke was
      performed. METHODS: Thirteen aphasic patients were H2(15)O PET-scanned twice at a
      one year interval during a word generation task. Patients are divided into two
      groups according to language performance for the word generation task at PET2.
      For the Good Recovery (GR) group, patients' performances are indistinguishable
      from those of normal subjects, while patients from the Poor Recovery (PR) group
      keep language disorders. Using SPM2, Language-Rest contrast is computed for both
      groups at both PET stages. Then, Session Effect contrast (TEP2-TEP1>0) is
      calculated for both groups. RESULTS: For the GR group, the Session Effect
      contrast shows an increase of activations in the left Postero-Superior Temporal
      Gyrus PSTG but also in the right thalamus and lenticular nuclei; for PR patients,
      the right lenticular nucleus activation is more important at PET1 than PET2.
      CONCLUSIONS: The crucial role of the left temporal activation is confirmed and
      its increase is linked to behavioural recovery. The role of the right basal
      ganglia to support good recovery from aphasia is a new finding. Their activation
      may be more task-dependant and related to inhibition of the right frontal cortex.

PMID- 20032915
TI  - Phantom limb related phenomena and their rehabilitation after lower limb
      amputation.
AB  - This paper reviewed the various hypotheses on phantom limb and phantom limb pain
      as well as all the related rehabilitation techniques to control these symptoms.
      The uncertainty in their pathophysiology strongly affects all the rehabilitation
      approaches so far used, as no single parameter has been found to predict or
      control phantom limb pain as well as no single factor can be quoted as an
      indicator of rehabilitation success for lower limb amputation. Within a
      comprehensive rehabilitation plan, behavioral interventions, stimulation
      techniques, feedback, physical therapies designed to possibly reverse the
      maladaptive memory traces and enhance its extinction have been described.
      Although substantially not clinically useful, pharmacological and surgical
      interventions also have been briefly considered. A reassessment of the actual
      strategies used is suggested with a role for rehabilitation not only after the
      amputation but also in the pre-emptive control of the pre-existing painful
      condition. In this process, rehabilitation should take into account many
      parameters, not always related to the traditional role of rehabilitation. Pain
      assessment before and after amputation, its natural history and clinical picture
      such as its quality, variations, level of the amputation, dominance, time
      interval between amputation and rehabilitation, as well as all the other phantom
      limb related phenomena should be considered and treated.

PMID- 20032916
TI  - Focus on flexed posture and hyperkyphosis: prevention and rehabilitation to
      reduce disability and increase quality of life.

PMID- 20032917
TI  - Understanding sagittal balance with a clinical perspective.
AB  - The sagittal plane of the spine has become an increasingly popular topic of
      discussion amongst healthcare professionals treating patients with spinal
      problems. The concepts surrounding the sagittal plane of the spine were initially
      investigated in detail in the French speaking world and French speakers continue
      to be at the forefront of investigations and debate that is now global. This
      review aims to clearly describe these concepts, define the terminology used and
      in particular make reference as to how this may impact on day to day clinical
      practice. In particular, the notion that our sagittal profile represents our own
      'spinal fingerprint' - individual to each an every one of us - is discussed in
      detail and how potential changes in this can lead to commonly seen conditions. A
      greater understanding by healthcare professionals of the human sagittal plane
      will hopefully lead to better understanding of the spine in physiological and
      pathological states.

PMID- 20032918
TI  - The rehabilitation of hyperkyphotic posture in the elderly.
AB  - The angle of thoracic kyphosis tends to increase with age resulting in
      hyperkyphosis in some individuals. While the term "kyphotic" is occasionally used
      to describe someone with accentuated thoracic curvature, hyperkyphosis is
      preferred since kyphosis itself refers to the normal sagittal angle of thoracic
      curvature. Epidemiolo-gic studies have demonstrated that age-related
      hyperkyphosis commonly affects the elderly population with estimates ranging from
      20% to 40%. In addition, hyperkyphosis affects a substantial number of older men.
      Apart from being a cosmetic deformity, older persons who suffer from
      hyperkyphosis are at increased risk for a variety of adverse health outcomes that
      include poor physical function, pulmonary compromise, falls, fractures, and even
      earlier mortality. Most clinicians and patients have assumed that thoracic
      hyperkyphosis is a result of underlying spinal osteoporosis, but approximately
      two thirds of those who are most hyperkyphotic don't have vertebral fractures.
      Over the past few years, there has been increased awareness and focus on
      potential effective treatments for age-related hyperkyphosis. Of these
      treatments, exercise based interventions and spinal orthoses are conservative
      rehabilitation management techniques that have shown promise in potentially
      improving health outcomes for affected patients. To date, all of these types of
      trials have been small in scale, and most short in duration. In the future,
      larger rigorously designed clinical trials will be needed to test and confirm the
      efficacy and feasibility of the most promising treatments for age-related
      hyperkyphosis. This invited review will discuss hyperkyphosis in terms of its
      etiology, clinical associations, and treatment in elderly individuals.

PMID- 20032919
TI  - Review of rehabilitation and orthopedic conservative approach to sagittal plane
      diseases during growth: hyperkyphosis, junctional kyphosis, and Scheuermann
      disease.
AB  - An increase of the physiological kyphosis during growth is defined hyperkyphosis
      (HK) and, according to the level where the apex of the curve can be retrieved, we
      can distinguish a thoracic HK and a thoraco-lumbar one, also called junctional
      kyphosis. Since these conditions can cause pain and esthetics impairments, lead
      in adulthood to an higher incidence of spinal and shoulder pain, and evolve
      during growth, it is important to manage this deformity. The aim of this paper
      was to present the state of the art about HK and its treatment. Scheuermann
      Disease (SCHK) is the better known cause of HK; other causes can be idiopathic or
      postural, trunk extensor muscles weakness or neurological problems. Despite
      etiology a specific treatment can be required during growth to prevent evolution
      and reach a better spinal alignment in adulthood. It is at the base of treatment
      and allow monitoring. There are some validated methods that can be used in a
      comprehensive rehabilitation approach. Evidence in this field is scanty, even if
      there is quite a consensus on possible treatments. They aim at improving posture
      and esthetics, and abolishing pain; they include: exercises, used mainly in
      mobile postural/idiopathic HK, and in SCHK without HK; braces (plus exercises, in
      this case aimed at reducing brace impairments), that in rigid HK and in most of
      SCHK patients also allow a better vertebral growth; surgery could be used in
      worst cases, even if it should be carefully considered, because it requires
      fusion and loss of spinal function.

PMID- 20032920
TI  - EJPRM systematic continuous update on Cochrane reviews in rehabilitation: news
      from the 3rd Issue 2009.
AB  - AIM: Since 2007 we have been focusing our attention to EJPRM as the best
      available clinical evidence as offered by the Cochrane Collaboration. Due to the
      absence of a specific Rehabilitation Group (only a Field does exist), some
      reviews in the field of PRM are not easy to find. Consequently, the EJPRM lists
      and presents all these reviews systematically. The aim of the present paper is to
      systematically review all the new papers in the field of rehabilitation published
      in the 3rd Issue of 2009 from the Cochrane Library in order to provide physicians
      a summary of the best updated evidence. METHODS: The authors systematically
      searched all the new papers of on rehabilitation from the 3rd Issue 2009 of the
      Cochrane Library. The retrieved papers have been divided in subgroups on the base
      of theirs topic and the Cochrane Groups. RESULTS: The number of included papers
      was 18, 14 of them being new reviews, 7 new reviews dealing with neurological
      rehabilitation, 4 dealing with musculoskeletal disorders, 3 dealing with pain
      management. In addition, 4 reviews have been updated, 1 in the field of
      musculoskeletal disorders, 2 on neuromuscular disorders, and 1 on elderly
      rehabilitation. The Cochrane Collaboration and the Cochrane Library are two
      important instruments to improve evidence-based medicine (EBM) in medical
      practice and in the field of rehabilitation. CONCLUSIONS: The present paper can
      help rehabilitation specialists to retrieve the findings of the most relevant and
      updated reviews in order to better their clinical practice.

PMID- 20032921
TI  - The clinical use of drugs influencing neurotransmitters in the brain to promote
      motor recovery after stroke; a Cochrane systematic review.
AB  - The objective of this review was to compare and to discuss the results of studies
      that investigated the ability of drugs to improve motor recovery after stroke by
      influencing dopamine, norepinephrine, or serotonin concentrations in the brain. A
      systematic literature search up to January 2009 was conducted in MEDLINE, Pubmed,
      EMBASE and in the database of the Cochrane Stroke Group Trial Register. In
      addition, the literature reference lists of the relevant publications were
      checked. The literature search was conducted in order to identify randomized
      controlled trials focusing on the effects of drugs on motor recovery after
      stroke. In order to structure the data, motor recovery was sub-divided into motor
      control and motor function. The methodological quality of the studies was also
      assessed. Six studies, investigating the effects of 7 different kinds of drugs
      were included. Methodological scores varied between 10 and 14 (max 19). Motor
      control was not influenced by any of the drugs. Motor function improved in
      patients treated with methylphenidate, trazodone, and nortriptyline. Results for
      fluoxetine and levodopa were contradicting. There is insufficient evidence to
      conclude that neuromodulating drugs targeting serotonin, norepinephrine, or
      dopamine influence motor recovery after stroke.

PMID- 20032922
TI  - PubMed reloaded: new interface, enhanced discovery.
AB  - The aim of this contribution was to present the redesigned version of the
      worldwide known PubMed interface. The changes relate to a simplified
      visualization, in order to require less efforts to find resources; they do not
      concern the functionalities or the search processing. This brief article will
      focus on the main differences between the old and the new version.

PMID- 20032923
TI  - Intent to receive influenza A (H1N1) 2009 monovalent and seasonal influenza
      vaccines - two counties, North Carolina, August 2009.
AB  - On September 15, 2009, the Food and Drug Administration approved the manufacture
      of four influenza A (H1N1) 2009 monovalent vaccines. Before release of the first
      batches of the vaccine on September 30, intent to receive the vaccine was
      estimated at 50% among selected U.S. adult populations and as high as 70% for
      children. However, studies in previous years of seasonal influenza vaccination in
      children, who might require 2 doses based on age and prior vaccination status,
      have indicated poor compliance with recommendations. To measure intent to receive
      H1N1 and seasonal influenza vaccines among children and adults, during August 28
      29, 2009, the North Carolina Center for Public Health Preparedness, with state
      and local public health officials, conducted a community assessment in two
      counties. This report summarizes the results of that assessment, which determined
      that 64% of adults reported intent to receive H1N1 vaccine. In addition, 65% of
      parents reported intent to have all their children (aged 6 months to <18 years)
      vaccinated with H1N1 vaccine, and 51% said they would have all their children
      vaccinated with both H1N1 and seasonal influenza vaccines. The most commonly
      reported reasons for not intending to receive H1N1 vaccine were belief in a low
      likelihood of infection (18%) and concern over vaccine side effects (14%); 85% of
      participants said they received their H1N1 information from television. To
      increase coverage with H1N1 and seasonal influenza vaccines, public health
      departments should use television to focus public health messages on the risks
      for infection and severe illness and the safety profile of the vaccine.

PMID- 20032924
TI  - Impact of seasonal influenza-related school closures on families - Southeastern
      Kentucky, February 2008.
AB  - During influenza epidemics, little is known about how influenza-related school
      closures affect families. Many children meet nutritional needs through school
      food programs, and schools provide child care both during and after school.
      Moreover, schools rely on student attendance to meet federal and state funding
      and educational requirements. To assess the impact of school closings on
      families, the Kentucky Department for Public Health (KDPH) conducted a telephone
      survey of randomly sampled households whose children attended schools in two
      adjacent school districts that had been closed because of high absenteeism during
      an outbreak of seasonal influenza in the community in February 2008. This report
      summarizes the results of that survey, which indicated that 97.0% of respondents
      agreed with the decision to close schools. In 29.1% of households, an adult had
      to miss work to provide child care, and in 15.7% of households, at least one
      adult lost pay because of missed work. Although the schools closed because of
      high absenteeism affecting school operations and funding, this was not fully
      communicated to families; 64.4% of respondents believed the closures would "keep
      people from getting ill," and 90.8% thought it was "extremely or very important"
      to disinfect schools while closed to reduce community spread of influenza. School
      districts and health departments should provide families with specific
      information about the reason for school closings and provide recommendations for
      reducing the spread of influenza while students are dismissed from school.

PMID- 20032925
TI  - Hantavirus pulmonary syndrome in five pediatric patients - four states, 2009.
AB  - Hantavirus pulmonary syndrome (HPS) is a reportable infectious disease with a
      high case-fatality rate, transmitted to humans by exposure to rodents. Each year,
      20--40 cases of HPS occur in the United States; cases in persons aged <17 years
      make up fewer than 7% of those cases, and cases in children aged <10 years are
      exceptionally rare. CDC received reports of five pediatric cases of HPS occurring
      during May 16--November 25, 2009, among children aged 6--14 years from Arizona,
      California, Colorado, and Washington. Three of the children were aged <10 years,
      and all five had exposure to rodents. This report summarizes the five cases,
      including the clinical findings and likely means of transmission of a hantavirus.
      Thrombocytopenia, elevated white blood cell (WBC) count, and pulmonary
      infiltrates were observed in all five children; elevated hematocrit was observed
      in three. One child died, and three of the four children who recovered required
      mechanical ventilation during hospitalization. Clinicians should consider HPS in
      the differential diagnosis for children with unexplained acute respiratory
      distress, especially if recent rodent exposure is noted. Public health agencies
      should promote preventive measures, including rodent control in housing and play
      areas, and children should be advised to avoid contact with rodents and areas of
      infestation.

PMID- 20032926
TI  - Coal workers' pneumoconiosis-related years of potential life lost before age 65
      years - United States, 1968-2006.
AB  - Coal workers' pneumoconiosis (CWP) is a preventable, slowly progressive
      parenchymal lung disease caused by inhalation and deposition of coal mine dust in
      the lungs. The incidence and rate of CWP progression is related to the amount of
      respirable coal dust to which miners were exposed during their working lifetime.
      Early pneumoconiosis can be asymptomatic, but advanced disease often leads to
      disability and premature death. To characterize the impact of premature mortality
      attributed to CWP in the United States, CDC's National Institute for Occupational
      Safety and Health (NIOSH) analyzed annual underlying cause of death data from
      1968-2006, the most recent years for which complete data were available. Years of
      potential life lost before age 65 years (YPLL), and mean YPLL were calculated
      using standard methodology. This report describes the results of that analysis,
      which indicate that during 1968-2006, a total of 22,625 YPLL were attributed to
      CWP (mean per decedent: 5.7). Annual YPLL attributed to CWP decreased 91.2%, from
      an average of 1,484 YPLL per year during 1968-1972 to 154 per year during 2002
      2006. However, annual YPLL from CWP have been increasing since 2002, from 135 in
      that year to 169 YPLL in 2006, suggesting a need for strengthening CWP prevention
      measures. CDC intends to maintain surveillance of CWP deaths to determine future
      trends and promote safer work environments.

PMID- 20032927
TI  - Measuring plasma membrane protein endocytic rates by reversible biotinylation.
AB  - Plasma membrane proteins are a large, diverse group of proteins comprised of
      receptors, ion channels, transporters and pumps. Activity of these proteins is
      responsible for a variety of key cellular events, including nutrient delivery,
      cellular excitability, and chemical signaling. Many plasma membrane proteins are
      dynamically regulated by endocytic trafficking, which modulates protein function
      by altering protein surface expression. The mechanisms that facilitate protein
      endocytosis are complex and are not fully understood for many membrane proteins.
      In order to fully understand the mechanisms that control the endocytic
      trafficking of a given protein, it is critical that the protein s endocytic rate
      be precisely measured. For many receptors, direct endocytic rate measurements are
      frequently achieved utilizing labeled receptor ligands. However, for many classes
      of membrane proteins, such as transporters, pumps and ion channels, there is no
      convenient ligand that can be used to measure the endocytic rate. In the present
      report, we describe a reversible biotinylation method that we employ to measure
      the dopamine transporter (DAT) endocytic rate. This method provides a
      straightforward approach to measuring internalization rates, and can be easily
      employed for trafficking studies of most membrane proteins.

PMID- 20032928
TI  - [Proctectomy with external sphincter preservation: long-term functional results].
AB  - 52 patients with the lower ampullary rectal cancer with tumor localization on the
      dentate line level had been operated with the use of the originally developed
      reconstructive technique, permitting preservation of the external anal sphincter
      elements and, consequently, partial continence. Colonic rectal pouch and smooth
      muscle cuff were performed during the neorectum and neoanus plasty. A protective
      stoma was performed in all cases. Contractive activity of saved elements of EAS
      improved with a course of time and squeezing anal pressure increased as well.
      Consequent continence improvement occurred during the first year after the stoma
      closure, biofeed-back therapy provided faster rehabilitation. The achieved long
      term functional results (73,4% actuarial 5-year disease-free survival) prove the
      oncological efficacy of the method on the strict assumption of indications
      observance. Thus, proctectomy with partial external anal sphincter preservation
      allows to avoid permanent colostomy and provides a satisfactory quality of life
      of the operated patients.

PMID- 20032929
TI  - [Diagnostics and surgical correction of postoperative myofascial defects of
      lateral abdominal wall and lumbar region].
AB  - Myofascial defects of lateral abdominal wall and lumbar region occur chiefly
      after lumbotomy--the most popular access in urosurgery. Meanwhile lumbotomy
      remains one of the most traumatic accesses through the lateral abdominal wall.
      Myofascial defects were diagnosed in 48,9% of operated patients with lumbotomy.
      Of them true postoperative hernias were found in 35,3%; neuropathic hernias - in
      13,6%. Since 2002 the originally developed method of lateral abdominal wall
      reconstruction had been used for the treatment of such patients. The immediate
      and long-term results (maximal follow-up period 5 years) showed no hernia
      recurrence or complications in 26 operated patients.

PMID- 20032930
TI  - [Quality of life before and after surgical treatment of duodenal ulcer].
AB  - The quality of life was studied in dependence of ulcer disease severity and type
      of surgery. Found out that it was in close correlation with the severity and
      duration of the disease and the presence of complications. Patients with sub- and
      decompensated ulcer stenosis showed the worst quality of life. Long-term results'
      study demonstrated that only organ-preserving operations, rather then gastric
      resection, allow adequate quality of life for the operated patients.

PMID- 20032931
TI  - [Gastrointestinal bleedings of non-ulcer etiology].
AB  - During the period of 2001-2007 yy., more then 2300 patients with gastrointestinal
      bleedings were treated. 53% of them were diagnosed with duodenal or gastric ulcer
      disease. The developed diagnostic algorithm provided the correct diagnose and
      treatment in 98,2% of patients. Advantages of miniinvasive and endovascular
      methods by treating of gastrointestinal bleedings were demonstrated.

PMID- 20032932
TI  - [Necrotic pancreatitis: treatment results].
AB  - The results of treatment of 310 patients with necrotic pancreatitis were analyzed
      to establish the efficacy of modern therapy strategy, defined on the 9th Russian
      congress of surgeons. Current treatment approaches were most effective in
      patients with severe forms of the pancreatitis. Demonstrated, that treatment
      protocol of patients with pancreonecrosis, who showed more then 8 points by
      APACHE II scale, should include pancreotropic antibiotic of broad spectrum,
      antisecretory drugs and early enteral nutrition. Patients with less then 8 points
      by APACHE II scale did not required the mandatory implementation of all the
      referred measurements.

PMID- 20032933
TI  - [Comparative analysis of horizontal venous reflux surgical correction by large
      trophic lower leg ulcers].
AB  - Subfascial perforant veins dissection (SPVD) of the lower leg was performed in
      patients with chronic venous insufficiency CEAP class 5 and 6. 252 operations
      were performed in 236 patients. All patients had trophic lesions (skin
      hyperpigmentation and lipodermatosclerosis) 218 (92,4%) patients had trophic
      lower leg ulcer to the time of operation. 30 patients had earlier performed
      phlebectomy. Open SPVD was performed in 122 cases, endoscopic technique was used
      in 114 patients. Comparative analysis of these two methods was performed. Long
      term results were accessed with the use of SF-36 questionnaire. Efficacy,
      pathogenetic validity and economic expedience of SPVD by large trophic lower leg
      ulcers are confirmed by the decrease of postoperative complications and
      recurrence rate. The horizontal venous reflux elimination and trophic ulcer
      dissection with intraoperative skin plasty allow a significant improvement of
      treatment results.

PMID- 20032934
TI  - [Laparoscopic reconstructive surgery by biliary tract malformations in children].
AB  - Treatment results of 18 children operated on various biliary tract malformations
      were analyzed. Laparoscopic portoenteroanastomosis by Kasai was performed in 10
      patients with biliary atresia aged from 10 days to 3,5 months. Average weight of
      the operated children was 3640 +/- 124 g. 8 patients aged from 2 to 15 years
      operated on cystic common bile duct malformation. Laparoscopic dissection of
      cystic deformated biliary ducts with Roux-en-Y hepaticoenterostomy was performed
      in these cases. 5 troacars were used for both operations. First stage of
      portoenteroanastomosis formation represented of laparoscopic portal fibrous plate
      separation. By cystic common bile duct malformations, altered bile ducts were
      dissected. The second stage--Roux-en-Y enteroenteroanastomosis--was performed
      through a paraumbilical microincision. Portal anastomosis or common bile duct
      anastomosis was performed also laparoscopically. Recovery of patients was
      observed in all cases. Early postoperative course demonstrated a low invasiveness
      of the method. Thus, laparoscopic access can become a method of choice in
      treatment of biliary tract malformations in children.

PMID- 20032935
TI  - [Puncture hystobiopsy with tissue telomerase activity measurement in preoperative
      thyroid nodes diagnostics].
AB  - Demonstrated, that puncture thyroid hystobiopsy is safe and informative method of
      preoperative thyroid nodes diagnostics. Telomerase activity in tissue samples was
      significantly higher in case of malignant thyroid disease, although a positive
      correlation of telomerase activity was also with the amount of lymphocytes in
      bioptates. Combination of thyroid hystobiopsy with tissue telomerase activity
      measurement proved to be an effective means of preoperative diagnostic of
      patients with nodular goiter.

PMID- 20032936
TI  - [Arterial celiac-mesenterial aberrations: comparative analysis of intraoperative
      data and CT-angiography].
AB  - 137 CT-angiograms of arterial celiac-mesenterial vessels were pro- and
      retrospectively analyzed in 120 patients. Radiological data was compared with
      intraoperative anatomy during standard and extended pancreatoduodenal resections.
      The analysis showed a considerable variability in architecture of celiac and
      superior mesenteric artery branches: hereby, a classical arterial anatomy was
      found only on 55% of the analyzed CT-scans. Intraoperative revision confirmed CT
      data in all cases. CT-angiography is a prompt and reliable method of celiac
      mesenterial arterial anatomy determination, making surgical treatment of patients
      with liver and pancreas diseases safer.

PMID- 20032937
TI  - [Treatment protocol of gastrointestinal bleedings].
AB  - 900 patients with gastrointestinal bleedings were included in the study. Basing
      on the endoscopic findings, prognosis for recurrent bleeding and clinical
      evaluation of the patients, diagnostic algorithm and treatment protocol were
      worked out. Use of forecasting system concerning the bleeding risk and clinical
      evaluation of the patients applying SAPS II for medical tactics choice allowed
      decreasing lethality from acute hemorrhage from 6.1 to 0.9%, in case of
      conservative treatment--from 4.5 to 1.0%, postoperative lethality--from 14.5% to
      0.

PMID- 20032938
TI  - [Immobilized forms of sodium hypochlorite in carboxymetilcellulose gel used in
      treatment of disseminated peritonitis].
AB  - 56 patients with disseminated purulent peritonitis were observed. All patients
      were divided into 2 groups. 30 patients treated according to traditional
      technique formed the first group. Surgical treatment included: laparotomy,
      elimination of the underlying condition that caused peritonitis, nasointestinal
      intubation of small intestine, abdominal cavity sanation with 0.02% furacillin
      solution till pure liquid, drainage. 200 ml of 0.03% aqueous solution of sodium
      hypochlorite was infused into abdominal cavity before closure. 26 patients
      treated according to the similar technique formed the second group. In contrast
      to the first group, 200 ml of immobilized form of sodium hypochlorite in
      carboxymetilcellulose gel was infused to the patients from the second group
      before wound closure. In early postoperative period the indices of endotoxicosis
      were in 1.6 times lower in patients from the second group and motor-evacuatory
      function of the stomach--twice higher compared with the patients from the first
      group. It decreased the amount of complications in 2 times, and postoperative
      lethality--in 2.6 times. In long-term postoperative period perfect treatment
      results increased in 20.8%, well--in 4.1%, tolerable--decreased in 20.9% compared
      with the results in the control group.

PMID- 20032939
TI  - [Repeated surgical operations for disseminated purulent peritonitis].
AB  - Results of surgical treatment were analyzed in 65 patients with disseminated
      purulent peritonitis (DPP). 34 patients undergoing re-laparotomy "on demand"
      formed the first group. 31 patients undergoing programmed re-laparotomy formed
      the second group. Lethality was higher in the first group (59% compared with 29%
      in the second group; p = 0.024). Risk of lethal outcome was higher in 2.5 times
      in patients from the first group (p = 0.030). Survival rate was evaluated using
      APACHE II scale, but the distinctions between two groups were not statistically
      significant (p = 0.178). According to APACHE II scale high indices were observed
      in deceased patients from both groups (26.1 +/- 8.9 in the first group, 19.7 +/-
      5.9 in the second group; p = 0.009). Indications for programmed planned abdominal
      cavity sanation and laparostoma surgery in patients with DPP are described.
      Authors suggest that programmed sanations substantially improve the results of
      treatment in patients with DPP compared with re-laparotomy "on demand".

PMID- 20032940
TI  - [Advantages and disadvantages of various surgical tactics in treatment of
      infected pancreonecrosis].
AB  - Comparative evaluation of various surgical tactics was carried out in 76 patients
      with infected pancreonecrosis treated during 2000-2007 years. It is estimated
      that application of staged necrosequestrectomies including programmed schedule of
      stage revisions and abdominal cavity and retroperitoneal sanations combined with
      open drainage allows decreasing lethality in patients with pancreatic infections
      compared to alternative surgical techniques.

PMID- 20032941
TI  - [Blood autologous transfusion at portal hypertension].
AB  - Preparation of auto-blood was performed for 140 patients with liver cirrhosis in
      the inactive phase. Not more than 200-300 ml of blood was taken from patients
      with cytopenia ("hypersplenism"), 400-450 ml--from patients with normal
      clinicobiochemical parameters. Besides autohemotransfusion, all patients
      underwent re-infusion of lost blood during the operation including the blood
      stored in the removed spleen. The volume of intra-operative hemorrhage varied
      from 200 to 1000 ml. The total volume of sampled blood amounted 44.2 L, 316 ml in
      average for one patient; 52 liters 880 ml were infused during the operation, 378
      ml--in average. Auto-blood application reduced intra-operative hemorrhage in 2
      times and number of postoperative complications--in 2.5 times.

PMID- 20032942
TI  - [Esophagogastric anastomosis insufficiency after esophagoplasty: prognosis and
      prophylaxis].
AB  - Results of surgical treatment were analyzed in 128 patients operated for
      esophageal carcinoma and gastric cancer involving the esophagus. The role of
      anastomosis type was specified among risk factors for anastomosis insufficiency;
      efficacy of cuff anastomosis in prophylaxis of insufficiency was statistically
      proved.

PMID- 20032943
TI  - [Surgical treatment of hiatal hernias].
AB  - 17 patients suffering from axial hiatal hernias with marked
      duodenogastroesophageal reflux underwent surgical treatment including selective
      proximal vagotomy combined with formation of closing cardia mechanism,
      enhancement in are flux function of pylorus, correction of duodenostasis.
      Specific postoperative complications and lethal outcomes were not observed.
      Increase of life quality was observed among patients in early and long-term
      postoperative periods in comparison with preoperative indices. Relapses or
      regurgitation disturbances were not observed either.

PMID- 20032944
TI  - [Diagnostics and thoracoscopic treatment of pleural empyema in younger children].
AB  - 174 children of all ages with acute destructive pneumonia complicated with
      pleural empyema were treated during 10 ten years using videothoracoscopic method;
      among them 74 children were of younger age (43%). General principles of modern
      diagnostics and videothoracoscopic pleural cavity sanations were formulated.
      Ultrasonography and computer tomography of the chest carried out in younger
      children give possibilities for clear differential diagnostics with other
      diseases. Advantages of endosurgical treatment are proved. Indications for
      planned recurrent pleural cavity sanations were worked out.

PMID- 20032945
TI  - [Economic efficacy of thoracoscopic treatment for pleural empyema in children].
AB  - Results of treatment carried out during 1989-2000 years were analyzed in 164
      children with pleural empyema. Economic analysis proves that videothoracoscopic
      pleural cavity sanation is more beneficial in acute period in 1.7 times and in
      long-term period--in 1.9 times, compared with traditional method (puncture and
      drainage). "Cost-efficacy" analysis shows that videothoracoscopic pleural cavity
      sanation allows increasing of clinical efficacy in 3.6 times in comparison with
      traditional treatment mode. "Cost-value" analysis shows improvement of life
      quality in 1.2 times after application of videothoracoscopic pleural cavity
      sanation compared with traditional method. Cost effectiveness of
      videothoracoscopic pleural cavity sanation for better life quality achievement is
      higher in 2.3 times compared with traditional method.

PMID- 20032946
TI  - [A comparative analysis of bronchus stump closure methods after pneumonectomy].
AB  - Original method of bronchus stump closure after pneumonectomy is presented.
      Developed compression bronchial suture was compared with manual Sweet suture and
      mechanical sutures in the experiment with 36 non-pedigreed dogs. Efficacy of
      different methods was evaluated basing on the clinical findings, radial,
      endoscopic and morphological observations. Macro- and microscopic investigations
      signify about the healing of main bronchus stump by primary intention with
      bronchial epithelium repair in the stump fundus under conditions of compression
      suture in 30 days after operation. It is ascertained that compression suture
      creates optimal conditions for stump repair compared with traditional manual and
      mechanical sutures healing by secondary intention.

PMID- 20032947
TI  - [The choice of surgical treatment for inguinal hernia].
AB  - Basing on the 30-year experience of prof. Yu.A. Nesterenko differential method of
      surgical treatment for inguinal hernias was worked out. The choice of surgical
      technique was based on the results of intra-operative revision of inguinal canal.
      Single-layer plasty of posterior wall was applied in case of insignificant
      destruction of tendinous structures; Shouldice plasty--in case of moderate
      changes; Moran plasty--in case of marked destruction, Lichtenstein plasty--in
      case of complete inguinal canal destruction. Analysis of long-term results showed
      low frequency of hernia relapses (1.4%) that can be compared with indices in
      specialized herniologic centers.

PMID- 20032948
TI  - [Clinical-electroneuromyographical characteristics of facial nerve paralysis in
      children].
AB  - A clinical-electroneuromyographical study of 40 children (32 (80%) of them aged
      from 12 to 17 years, mean age 13,9+/-1,8 years, and 8 (20%) - from 1 to 8 years,
      mean age 4,4+/-2,1 years) were studied in the acute period of facial nerve
      paralysis (FNP). Six (15%) children had FNP in the anamnesis. Among precipitating
      factors were the cold exposure the day before disease onset (20 (50%) patients),
      symptoms of flu (13 (32,5%) patients) and psycho-emotional tension (3 (7,5%)
      patients). No precipitation was noted in 4 (10%) children. The degree of muscle
      paresis was 81,9+/-7% that corresponded to clinical stages III-IV according to K.
      Rosler. An electroneuromyographical analysis of motor ortho- and antidromic
      response to the facial nerve stimulation on the side of paresis and on the
      contralateral side in patients and controls revealed the presence of proximal
      axon- and myelinopathy of facial nerve with the involvement of its own
      motorneurons and brain stem interneurons. The maintenance of wink reflex and F
      wave blocks in the period over 3 weeks are prognostically unfavorable factors for
      restoration of mimic muscle function in the early stage of disease.

PMID- 20032949
TI  - [Peculiarities of cognitive functions in patients with chronic back pain].
AB  - The authors have studied cognitive functions and influencing factors in 64
      patients with chronic low back pain. All patients have been examined using
      neurologic, neuroorthopedic, pathopsychological and neuropsychological methods.
      Patients have been divided into 2 groups according to their age: group 1 (aged 30
      50 years) and group 2 (aged 51-60 years). Healthy controls were matched to
      patients for age, sex and education. Significant differences in
      neuropsychological testing, i.e. mental flexibility, delayed memory, psychomotor
      speed, which referred to the subtle cognitive impairment with executive function
      disturbances, were found in both groups of patients with chronic low back pain as
      compared to pain-free adults. Sensory-discriminative (pain intensity) and
      affective-emotional (negative emotions, in particular, anxiety) characteristics
      had the effect on cognitive functions in younger patients without depressive
      symptoms. Affective-emotional (anxiety, psychological distress) and cognitive
      characteristics (i.e. catastrophising) contributed to the cognitive disturbances
      in older patients.

PMID- 20032950
TI  - [Peculiarities of organic psychic infantilism in adolescents].
AB  - An aim of the study was to specify peculiarities of the clinical dynamics of
      organic psychic infantilism and psychopathological presentations of this disorder
      in adolescence. A significant prevalence of psychic infantilism caused by organic
      CNS damage in patients seeking psychiatric help in adolescence and a negative
      effect of this disorder on social adaptation in this period of life were found.
      Sixty-seven patients, aged 15-18 years, (ICD-10 diagnosis F06) with signs of
      psychic infantilism were studied. In these cases, psychic infantilism encompassed
      all aspects of mental activity and manifested itself as a constant personality
      trait that caused the infantile type of reaction to the most of life situations.
      The clinical heterogeneity of organic infantilism determined by the different
      degree of psychic immaturity in some areas of psychic activity and concomitant
      encephalopathy symptoms was noted. This allowed to single out 3 groups of
      patients: with domination of psychic infantilism in volition (28 patients), in
      emotional sphere (21 patients) and immaturity of cognitive functions (20
      patients). The clinical heterogeneity of psychic infantilism likely reflects the
      character of CNS damage (localization and time of the damage) and specifics of
      related organic dysontogenesis.

PMID- 20032951
TI  - [Reproductive potential of women with epilepsy].
AB  - An aim of the article was to study reproductive health of 218 women with epilepsy
      who were long-term treated with antiepileptic drugs (AED). A comparison group
      included 47 patients with polycystic ovary syndrome (PCOS). Women with epilepsy
      were stratified into 2 groups: group 1 included 107 women of reproductive age and
      group 2 - 111 pregnant women with epilepsy. In group 1, 27,7% women had ovary
      dysfunction, 7,2% - hypoprogesteronemia and 27% - hyperprolactinemia. There was
      no signs characteristic of diagnosis of PCOS in women with epilepsy compared to
      the women with PCOS. Menstrual cycle disturbances were reversible. The pregnant
      women were stratified into 2 subgroups: subgroup A consisted of women who were
      prepared for pregnancy by the epileptologist, subgroup B included women with
      unplanned pregnancy. The comparative study of the pregnancy course in these
      subgroups revealed that in subgroup A the compliance to treatment was higher and
      pregnancy and delivery were more successful as compared to subgroup B. Preparing
      for pregnancy and its planning together with epileptologist allows to control for
      seizures using minimal doses of AED and decreases pregnancy and delivery
      complications.

PMID- 20032952
TI  - [Failed back syndrome in patients after the surgery for compressive lumbosacral
      radiculopathy].
AB  - A study of 80 patients after the surgery for compressive lumbosacral
      radiculopathy revealed that myogenic trigger zones and skin zones of hyperalgesia
      in lumbar and low extremities on the side of radicular compression and the
      contralateral side were formed before the surgery. Trigger zones remained in the
      latent state after the surgery in 33 patients who had no anxiety and depressive
      symptoms before the operation. These zones were treated with exercises (a fitness
      program). Symptoms of anxiety and depression that predict the relapse of pain in
      the post-surgery period were noted in 47 patients. The relapse of pain followed
      the <<blazed way>> in these patients but it was caused by the pain conditioned by
      trigger zones formed before the surgery in the insufficiency of the
      antinociceptive system. Moreover, an iatrogenic zone emerged in the post-surgery
      scar. Treatment of this group of patients should include antidepressants
      (velaxin), local anesthetics (novocaine, plasters with 5% lidocaine gel) and
      later - a fitness program.

PMID- 20032953
TI  - [Efficacy and tolerability of choline alphoscerate (cereton) in patients with
      Parkinson's disease with cognitive disorders].
AB  - An open 10-day study of treatment effect of cereton in comparison to piracetam
      has been conducted. Cereton was used in 40 patients (main group) in dosage 1000
      mg, piracetam - in 20 patients (control group) in dosage 2000 mg. Both drugs were
      used intravenous in drops in 200 ml of physiologic saline along with
      antiparkinsonian medications. Patient's state was assessed with a battery of
      psychometric scales and neuropsychological tests as well as with instruments for
      measuring intensity of parkinsonian symptoms, side-effects and quality of life.
      Marked and moderate improvement of cognitive functions was found in patients of
      the main group compared to the control one (40% and 25%, respectively, p<0,05).
      Deterioration of cognitive functions was seen less often in the main group than
      in the control group (5% and 15%, respectively, p<0,05). Cereton was well
      tolerated by patients. Side effects (brief and short-term) were found only in 6
      (15%) patients.

PMID- 20032955
TI  - [Attention deficit hyperactivity disorder: the role of parent and teacher
      questionnaire in the assessment of patient's social-psychological adaptation].
AB  - Parents and teachers of 342 school children, aged from 7 to 11 years, were
      questioned with the <<Strenghts and Difficulties Questionnaire>> (SDQ) using non
      randomized method. The following comparative analysis of SDQ items measured in
      parents and teachers of children with ADHD and age-matched controls was carried
      out. It has been shown that the spectrum of disturbances characteristic of ADHD
      is not confined only to main symptoms of ADHD. The results of questionnaire of
      both parents and teachers indicated the marked intensity of emotional
      disturbances, behavioral problems and difficulties in interactions with peers as
      well as the underdevelopment of social trends in behavior in children with ADHD
      compared to the controls. The data obtained confirm the necessity of treatment
      extension beyond the core symptoms with considering more general parameters of
      the patients quality of life.

PMID- 20032954
TI  - [Open randomized comparative twelve-week study of lithium and valproate in manic
      episode].
AB  - One hundred and twenty-five patients (49 men and 76 women, mean age 38,0+/-12,5
      years) were randomized in two groups. One group (64 patients) was treated with
      valproate sodium and another group (61 patients) received lithium carbonate.
      Monotherapy was administered with the mean dose of valproate 20 mg/kg/day (serum
      valproate concentration between 70 and 125 ?g/ml) and the mean dose of lithium
      800 mg/day (between 600 and 900 mg/day; serum lithium concentration 0,8-1,2
      mmol/L) during 12 weeks. Clinical effectiveness was assessed using YMRS, CGI-BP
      and MADRS at 0, 5th, 10th, 21st , 84th days of treatment. The number of
      responders (50% reduction in YMRS scores) was 51,7% (30 patients) in lithium
      group and 56,7% (34 patients) in valproate group by the 21st day (p=0,59).The
      mean reduction in YMRS scores was 11,6 in patients treated with lithium and 12,3
      in patients treated with valproate. By the 84th day (LOCF), the number of
      responders reached 85% (51 patients) in lithium group and 90,3% (56 patients) in
      valproate group (p=0,37). The mean reduction in YMRS scores was 19,4 in patients
      treated with lithium and 19,6 in patients treated with valproate. The average
      reduction in MADRS scores was -1,4 (p=0,08) and -2,2 (p=0,001) in lithium group; 
      1,6 (p=0,002) and -1,4 (p=0,019) in valproate group on the 21st and 84th days.
      Adverse effects were observed in 8 (13,1%) patients who received lithium and 3
      patients (4,7%) who received valproate (p=0,12). The most common of them were
      tremor, nausea, dry mouth. There were no clinically significant abnormalities in
      laboratory values, vital functions and EEG. In conclusion, the results
      demonstrated equal therapeutic efficacy, tolerability and safety of valproate and
      lithium in the treatment of manic episodes in patients with bipolar disorder.

PMID- 20032956
TI  - [The therapy of patients with dizziness and balance disorders].
AB  - A new computerized method is proposed for correction and inhibition of
      unfavorable illusory (dizziness), vestibular-oculomotor (nystagmus) and
      vestibular-postural (balance) which allows to teach a subject to block
      generalization of an afferent signal to effector mechanisms of the central
      nervous system by developing a fixation reflex, employing a delayed feedback. Two
      ways of using this method were employed depending on the kind of stimulation
      programs aimed at inducing abnormal responses of a certain sensory modality
      (visual or vestibular). The study involved 24 patients with vestibulopathies of
      peripheral and central origin divided into 2 equal groups one of which had been
      taught by a visual technique, the other - by a vestibular one. The method allows
      to produce abnormal illusory and vestibular optic oculomotor responses in the
      patient and inhibit them with the help the fixation reflex development. The
      visual way of correction was the most effective for patients with peripheral
      vestibulopathia and the vestibular way - for patients with central
      vestibulopathia.

PMID- 20032957
TI  - [Arterial and venous brain reactivity in the acute period of brain concussion].
AB  - Arterial and venous brain reactivity has been studied in 38 patients in the acute
      period of brain concussion (BC) and 32 healthy volunteers using transcranial
      color duplex scanning of brain vessels. The assessment of arterial inflow was
      conducted for the medial brain artery (MBA) and that of venous outflow - for the
      basal vein (BV) of Rosenthal. Hyperkinetic and orthostatic probes were used for
      assessment of cerebrovascular reactivity. BC was not accompanied by marked
      changes of cerebral resting hemodynamic parameters. The increase of peak blood
      flow velocity in MBA in the acute period which is characteristic of the brain
      hyperinfusion was found in 20% of patients and that in BA compensating the
      disturbed outflow along the surface brain system - in 25% of patients. In
      normalcy, the brain venous reactivity to hypercapnia was higher than arterial one
      and that to orthostasis corresponded to the intensity of arterial changes. The
      lack of quantitative differences in the reaction of arterial and venous blood
      flow to hypercapnia and the predominance of venous reactivity value in
      orthostasis in patients with BC suggest the disturbance of venous tone regulation
      in these patients.

PMID- 20032958
TI  - [Potentialities of neuropsychological methods for investigation of alcoholism].
AB  - Results from a sample of 411 alcohol dependent patients and healthy controls
      showed diagnostic potentialities of neuropsychological methods for investigation
      aimed at discovering of disturbances of higher psychic functions indicative of
      organic brain lesions. The proposed standardized neuropsychological technique is
      a sufficiently sensitive instrument not only for revealing minimal brain
      deficiency linked to chronic alcoholic intoxication but also for the evaluation
      of its intensity, diffuseness, localization of organic brain lesion. The complex
      analysis of above-listed indicators allows to determine if these disturbances are
      specific or nonspecific for alcoholism. This method also increases the
      effectiveness of diagnosis of minimal brain deficiency in patients with alcohol
      dependence and can be used for solution of theoretical problems.

PMID- 20032959
TI  - Deletion of H-Ras decreases renal fibrosis and myofibroblast activation following
      ureteral obstruction in mice.
AB  - Tubulointerstitial fibrosis is characterized by the presence of myofibroblasts
      that contribute to extracellular matrix accumulation. These cells may originate
      from resident fibroblasts, bone-marrow-derived cells, or renal epithelial cells
      converting to a mesenchymal phenotype. Ras GTPases are activated during renal
      fibrosis and play crucial roles in regulating both cell proliferation and TGF
      beta-induced epithelial-mesenchymal transition. Here we set out to assess the
      contribution of Ras to experimental renal fibrosis using the well-established
      model of unilateral ureteral obstruction. Fifteen days after obstruction, both
      fibroblast proliferation and inducers of epithelial-mesenchymal transition were
      lower in obstructed kidneys of H-ras knockout mice and in fibroblast cell lines
      derived from these mice. Interestingly, fibronectin, collagen I accumulation,
      overall interstitial fibrosis, and the myofibroblast population were also lower
      in the knockout than in the wild-type mice. As expected, we found lower levels of
      activated Akt in the kidneys and cultured fibroblasts of the knockout. Whether
      Ras inhibition will turn out to prevent progression of renal fibrosis will
      require more direct studies.

PMID- 20032960
TI  - T cells and dendritic cells in glomerular disease: the new glomerulotubular
      feedback loop.
AB  - A newly described glomerulotubular feedback loop may explain the relationship
      between glomerular damage, epitope spreading, tubulointerstitial nephritis,
      proteinuria as a progression factor, and the importance of the local milieu in
      kidney damage. It also opens the horizons for exciting innovative approaches to
      therapy of both acute and chronic kidney diseases.

PMID- 20032961
TI  - Acute kidney injury in non-severe pneumonia is associated with an increased
      immune response and lower survival.
AB  - While sepsis is a leading cause of acute kidney injury in critically ill
      patients, the relationship between immune response and acute kidney injury in
      less severely ill patients with infection is not known. Here we studied the
      epidemiology, 1-year mortality, and immune response associated with acute kidney
      injury in 1836 hospitalized patients with community-acquired severe and non
      severe pneumonia. Acute kidney injury developed in 631 patients of whom 329 had
      severe and 302 had non-severe sepsis. Depending on the subgroup classification,
      16-25% of the patients with non-severe pneumonia also developed acute kidney
      injury. In general, patients with acute kidney injury were older, had more
      comorbidity, and had higher biomarker concentrations (interleukin-6, tumor
      necrosis factor, D-dimer) even among patients without severe sepsis. The risk of
      death associated with acute kidney injury varied when assessed by Gray's survival
      model and after adjusting for differences in age, gender, ethnicity, and
      comorbidity. This risk was significantly higher immediately after hospitalization
      but gradually fell over time in the overall cohort and in those with non-severe
      pneumonia. A significantly higher risk of death (hazard ratio 1.29) was also
      present in those never admitted to an intensive care unit. Hence acute kidney
      injury is common even among patients with non-severe pneumonia and is associated
      with higher immune response and an increased risk of death.

PMID- 20032963
TI  - Sugar-sweetened soda consumption, hyperuricemia, and kidney disease.
AB  - The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead
      to elevations in uric acid levels. Here we determined whether soda drinking is
      associated with hyperuricemia and, as a potential consequence, reduced kidney
      function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities
      Study completed a dietary questionnaire and had measurements of their serum
      creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds
      ratios from logistic regressions for binary outcome of hyperuricemia and chronic
      kidney disease (eGFR less than 60 ml/min per 1.73 m(2)) were evaluated. Compared
      to participants who drank less, consumption of over one soda per day was
      associated with increased odds of prevalent hyperuricemia and chronic kidney
      disease. The odds ratio for chronic kidney disease significantly increased to
      2.59 among participants who drank more than one soda per day and had a serum uric
      acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than
      one soda per day was not associated with hyperuricemia or chronic kidney disease.
      Neither preexistent hyperuricemia nor development of hyperuricemia modified the
      lack of association between soda drinking and incident chronic kidney disease.
      Thus our study shows that high consumption of sugar-sweetened soda was associated
      with prevalent but not incident hyperuricemia and chronic kidney disease.

PMID- 20032964
TI  - Long-term study of mycophenolate mofetil treatment in IgA nephropathy.
AB  - Since the efficacy of mycophenolate mofetil (MMF) to treat immunoglobulin A (IgA)
      nephropathy is controversial, we extended our original study by following 40
      Chinese patients with established IgA nephropathy for 6 years. All patients were
      maintained on their angiotensin blockade medication and half were randomized to
      receive MMF for 6 months. After 6 years, 11 patients required dialysis (2 from
      the MMF and 9 from the control group). Significantly, only 3 treated (as compared
      to 10 control) patients reached the composite end point of serum creatinine
      doubling or end-stage renal disease. Linear regression showed the annualized
      decline in the estimated glomerular filtration rate was significantly less in the
      MMF-treated group. Urinary protein excretion and the albumin-to-creatinine ratio
      were lower with MMF treatment during the first 24 months, beyond which there was
      no difference between groups. Multivariable Cox regression analysis showed that
      the baseline estimated glomerular filtration rate and proteinuria, and change in
      the urine albumin-to-creatinine ratio at 1 year to be important predictors of
      progression to end-stage renal disease. We found that among Chinese patients with
      IgA nephropathy who had mild histologic lesions and persistent proteinuria
      despite maximal angiotensin blockade, MMF treatment may result in transient and
      partial remission of proteinuria in the short-term and renoprotection in the long
      term.

PMID- 20032962
TI  - Major contribution of tubular secretion to creatinine clearance in mice.
AB  - This study was performed to quantify the fraction of excreted creatinine not
      attributable to creatinine filtration for accurately determining the glomerular
      filtration rate in mice. To measure this we compared creatinine filtration with
      the simultaneous measurement of inulin clearance using both single-bolus
      fluorescein isothiocyanate (FITC)-inulin elimination kinetics and standard FITC
      inulin infusion. During anesthesia, creatinine filtration was found to be
      systematically higher than inulin clearance in both male and female C57BL/6J
      mice. The secretion fraction was significantly less in female mice.
      Administration of either cimetidine or para-aminohippuric acid, competitors of
      organic cation and anion transport respectively, significantly reduced the
      secretion fraction in male and female mice and both significantly increased the
      plasma creatinine level. Creatinine secretion in both genders was not mediated by
      the organic cation transporters OCT1 or OCT 2 since secretion fraction levels
      were identical in FVB wild-type and OCT1/2 knockout mice. Thus, secretion
      accounts for about 50 and 35% of excreted creatinine in male and female mice,
      respectively. Increasing plasma creatinine threefold by infusion further
      increased the secretion fraction. Renal organic anion transporter 1 mRNA
      expression was higher in male than in female mice, reflecting the gender
      difference in creatinine secretion. Hence we show that there is a major secretory
      contribution to creatinine excretion mediated through the organic anion transport
      system. This feature adds to problems associated with measuring endogenous
      creatinine filtration in mice.

PMID- 20032965
TI  - The pelvis-kidney junction contains HCN3, a hyperpolarization-activated cation
      channel that triggers ureter peristalsis.
AB  - Peristaltic waves of the ureteric smooth muscles move urine down from the kidney,
      a process that is commonly defective in congenital diseases. To study the
      mechanisms that control the initiation and direction of contractions, we used
      video microscopy and optical mapping techniques and found that electrical and
      contractile waves began in a region where the renal pelvis joined the connective
      tissue core of the kidney. Separation of this pelvis-kidney junction from more
      distal urinary tract segments prevented downstream peristalsis, indicating that
      it housed the trigger for peristalsis. Moreover, cells in the pelvis-kidney
      junction were found to express isoform 3 of the hyperpolarization-activated
      cation on channel family known to be required for initiating electrical activity
      in the brain and heart. Immunocytochemical and real-time PCR analyses found that
      hyperpolarization-activated cation-3 is expressed at the pelvis-kidney junction
      where electrical excitation and contractile waves originate. Inhibition of this
      channel caused a loss of electrical activity at the pelvis-kidney junction and
      randomized the origin of electrical activity in the urinary tract, thus markedly
      perturbing contractions. Collectively, our study demonstrates that
      hyperpolarization-activated cation-3 channels play a fundamental role in
      coordinating proximal-to-distal peristalsis of the upper urinary tract. This
      provides insight into the genetic causes of common inherited urinary tract
      disorders such as reflux and obstruction.

PMID- 20032966
TI  - Dopaminergic signaling mediates the motivational response underlying the opponent
      process to chronic but not acute nicotine.
AB  - The mesolimbic dopamine (DA) system is implicated in the processing of the
      positive reinforcing effect of all drugs of abuse, including nicotine. It has
      been suggested that the dopaminergic system is also involved in the aversive
      motivational response to drug withdrawal, particularly for opiates, however, the
      role for dopaminergic signaling in the processing of the negative motivational
      properties of nicotine withdrawal is largely unknown. We hypothesized that
      signaling at dopaminergic receptors mediates chronic nicotine withdrawal
      aversions and that dopaminergic signaling would differentially mediate acute vs
      dependent nicotine motivation. We report that nicotine-dependent rats and mice
      showed conditioned place aversions to an environment paired with abstinence from
      chronic nicotine that were blocked by the DA receptor antagonist alpha
      flupenthixol (alpha-flu) and in DA D(2) receptor knockout mice. Conversely, alpha
      flu pretreatment had no effect on preferences for an environment paired with
      abstinence from acute nicotine. Taken together, these results suggest that
      dopaminergic signaling is necessary for the opponent motivational response to
      nicotine in dependent, but not non-dependent, rodents. Further, signaling at the
      DA D(2) receptor is critical in mediating withdrawal aversions in nicotine
      dependent animals. We suggest that the alleviation of nicotine withdrawal
      primarily may be driving nicotine motivation in dependent animals.

PMID- 20032967
TI  - Treatment strategies targeting excess hippocampal activity benefit aged rats with
      cognitive impairment.
AB  - Excess neural activity in the CA3 region of the hippocampus has been linked to
      memory impairment in aged rats. We tested whether interventions aimed at reducing
      this excess activity would improve memory performance. Aged (24 to 28 months old)
      male Long-Evans rats were characterized in a spatial memory task known to depend
      on the functional integrity of the hippocampus, such that aged rats with
      identified memory impairment were used in a series of experiments. Overexpression
      of the inhibitory neuropeptide Y 13-36 in the CA3 via adeno-associated viral
      transduction was found to improve hippocampal-dependent long-term memory in aged
      rats, which had been characterized with impairment. Subsequent experiments with
      two commonly used antiepileptic agents, sodium valproate and levetiracetam,
      similarly produced dose-dependent memory improvement in such aged rats. Improved
      spatial memory with low doses of these agents was observed in both appetitve and
      aversive spatial tasks. The benefits of these different modalities of treatment
      are consistent with the concept that excess activity in the CA3 region of the
      hippocampus is a dysfunctional condition that may have a key role underlying age
      related impairment in hippocampal-dependent memory processes. Because increased
      hippocampal activation occurs in age-related memory impairment in humans as
      observed in functional neuroimaging, the current findings also suggest that low
      doses of certain antiepileptic drugs in cognitively impaired elderly humans may
      have therapeutic potential and point to novel targets for this indication.

PMID- 20032968
TI  - Prototypic GABA(A) receptor agonist muscimol acts preferentially through
      forebrain high-affinity binding sites.
AB  - Muscimol has been regarded as a universal agonist for all gamma-aminobutyric acid
      type A receptor (GABA(A)-R) subtypes. However, brain regional distribution of
      muscimol's high-affinity binding sites greatly differs from those of other
      binding sites of the GABA(A)-R. To test whether behavioral effects of muscimol
      correlated with the density of high-affinity [(3)H]muscimol binding, we examined
      several GABA(A)-R subunit gene-modified mouse lines: alpha1, alpha4, or delta
      knockouts (KO), alpha4+delta-double KO, and Thy1.2 promoter-driven alpha6
      transgenic mice (Thy1alpha6). We determined the high-affinity [(3)H]muscimol
      binding in brain sections by quantitative autoradiography and sedative/ataxic
      effects induced in vivo by muscimol using a constant speed rotarod. alpha4-KO
      mice had reduced [(3)H]muscimol binding in the caudate-putamen, thalamus, and
      hippocampus, and were less sensitive to the behavioral impairment by muscimol.
      Similarly, delta-KO mice also had reduced binding to forebrain regions and a
      lower behavioral sensitivity to muscimol than their wild-type controls. In
      contrast, alpha1-KO mice had unaltered behavioral sensitivity to muscimol and
      unaltered [(3)H]muscimol binding, even though previous studies have demonstrated
      dramatically reduced binding to various other GABA(A)-R sites in these mice.
      Finally, Thy1alpha6 mice exhibited increased behavioral sensitivity to muscimol,
      and to another direct GABA-site agonist gaboxadol, and increased [(3)H]muscimol
      binding in the cerebral cortex and hippocampus. Thus, the differences in sedative
      and motor-impairing actions of muscimol in various mouse models correlated with
      the level of forebrain high-affinity [(3)H]muscimol binding. These data suggest
      that a small special population of GABA(A)-Rs, most likely extrasynaptic non
      alpha1-containing receptors, strongly contributes to the in vivo pharmacological
      effects of muscimol.

PMID- 20032969
TI  - Repetitive self-grooming behavior in the BTBR mouse model of autism is blocked by
      the mGluR5 antagonist MPEP.
AB  - Autism is a neurodevelopmental disorder characterized by abnormal reciprocal
      social interactions, communication deficits, and repetitive behaviors with
      restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows
      robust behavioral phenotypes with analogies to all three of the diagnostic
      symptoms of autism, including well-replicated deficits in reciprocal social
      interactions and social approach, unusual patterns of ultrasonic vocalization,
      and high levels of repetitive self-grooming. These phenotypes offer
      straightforward behavioral assays for translational investigations of
      pharmacological compounds. Two suggested treatments for autism were evaluated in
      the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of
      the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the
      Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with
      autistic features. Risperidone has been approved by the United States Food and
      Drug Administration for the treatment of irritability, tantrums, and self
      injurious behavior in autistic individuals. We evaluated the actions of MPEP and
      risperidone on two BTBR phenotypes, low sociability and high repetitive self
      grooming. Open field activity served as an independent control for non-social
      exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with
      high sociability and low self-grooming, served as the strain control. MPEP
      significantly reduced repetitive self-grooming in BTBR, at doses that had no
      sedating effects on open field activity. Risperidone reduced repetitive self
      grooming in BTBR, but only at doses that induced sedation in both strains. No
      overall improvements in sociability were detected in BTBR after treatment with
      either MPEP or risperidone. Our findings suggest that antagonists of mGluR5
      receptors may have selective therapeutic efficacy in treating repetitive
      behaviors in autism.

PMID- 20032970
TI  - New insights into innate immune mechanisms underlying allergenicity.
AB  - Allergic diseases, which have reached epidemic proportions, are caused by
      inappropriate immune responses to a relatively small number of environmental
      proteins. The molecular basis for the propensity of specific proteins to promote
      maladaptive, allergic responses has been difficult to define. Recent data suggest
      that the ability of such proteins to promote allergic responses in susceptible
      hosts is a function of their ability to interact with diverse pathways of innate
      immune recognition and activation at mucosal surfaces. This review highlights
      recent insights into innate immune activation by allergens--through proteolytic
      activity, engagement of pattern recognition receptors, molecular mimicry of TLR
      signaling complex molecules, lipid-binding activity, and oxidant potential--and
      the role of such activation in inducing allergic disease. A greater understanding
      of the fundamental origins of allergenicity should help define new preventive and
      therapeutic targets in allergic disease.

PMID- 20032971
TI  - CD11c as a transcriptional biomarker to predict response to anti-TNF monotherapy
      with adalimumab in patients with rheumatoid arthritis.
AB  - We performed transcription profiling using monocytes to identify predictive
      markers of response to anti-tumor necrosis factor (anti-TNF) therapy in patients
      with rheumatoid arthritis (RA). Several potential predictors of response were
      identified, including CD11c. Validation in samples from independent cohorts
      (total of n = 27 patients) using reverse transcription-PCR confirmed increased
      expression of CD11c in responders to adalimumab (100% sensitivity; 91.7%
      specificity, power 99.6%; alpha = 0.01). Pretherapy CD11c levels significantly
      correlated with the response criteria as defined by the American College of
      Rheumatology (ACR) (r = 0.656, P < 0.0001). However, CD11c was neither predictive
      of response to methotrexate (MTX) alone (n = 34) nor to MTX in combination with
      adalimumab (n = 16). Clinical responders revealed a reset to a normal expression
      pattern of resident/inflammatory monocyte markers, which was absent in
      nonresponders. Therefore, an analysis of key cell types identifies potentially
      predictive biomarkers that may help to restrict the use of adalimumab to therapy
      responders. Larger studies, including studies of monotherapy with other drugs,
      are now needed to confirm and validate the specificity of CD11c for anti-TNF
      biologics.

PMID- 20032973
TI  - FDA regulation of dietary supplements and requirements regarding adverse event
      reporting.
AB  - In 1994, the Dietary Supplement Health and Education Act (DSHEA) amended the
      Federal Food, Drug, and Cosmetic Act (FDC Act) to set up a distinct regulatory
      framework for what we now call dietary supplements. The DSHEA was passed with the
      intent of striking a balance between providing consumers access to safe dietary
      supplements to help maintain or improve their health and giving the US Food and
      Drug Administration (FDA) authority to regulate and take action against
      manufacturers of supplements or supplement ingredients that present safety
      problems, are presented with false or misleading claims, or are adulterated or
      misbranded. This article will present FDA's recent experience in collecting and
      evaluating dietary supplement adverse event data for the purpose of assuring the
      public that the dietary supplements they purchase are safe.

PMID- 20032972
TI  - Pharmacokinetics of 23-epi-26-deoxyactein in women after oral administration of a
      standardized extract of black cohosh.
AB  - Dietary supplements containing black cohosh are alternatives to conventional
      hormone replacement therapy in menopause. This study investigates the maximum
      tolerated dose of a 75% ethanol extract of black cohosh and determines the
      pharmacokinetics of one of its most abundant triterpene glycosides, 23-epi-26
      deoxyactein. Single doses of black cohosh extract containing 1.4, 2.8, or 5.6 mg
      of 23-epi-26-deoxyactein were administered to 15 healthy, menopausal women.
      Serial blood samples and 24-h urine samples were obtained; blood chemistry,
      hormonal levels, and 23-epi-26-deoxyactein levels were determined. No acute
      toxicity or estrogenic hormone effects were observed. Pharmacokinetic analyses of
      23-epi-26-deoxyactein in sera indicated that the maximum concentration and area
      under the curve increased proportionately with dosage, and that the half-life was
      ~2 h for all dosages. Less than 0.01% of the 23-epi-26-deoxyactein was recovered
      in urine 24 h after administration. No phase I or phase II metabolites were
      observed either in clinical specimens or in vitro.

PMID- 20032974
TI  - A comprehensive approach to identifying and authenticating botanical products.
AB  - Whether they are being taken as dietary supplements by the general public or
      being evaluated in a clinical study, the authenticity of botanical products is a
      matter of paramount concern. Botanical specimens and the dietary supplements
      derived from them can vary in quality and in chemical constituent profiles
      because of a number of factors. Subtle variations in botanical specimens are
      known to have profound effects on the quality, efficacy, and safety of botanical
      dietary supplements and can potentially alter the results of clinical studies
      that rely on these materials. A complete array of authentication and evaluation
      tools can be utilized to provide a well-rounded scientific approach to the
      authentication of botanical products. It is vital that the authenticity of
      botanical supplements be established using appropriate analysis tools regardless
      of whether the end products are being considered for evaluation in clinical
      studies or are being developed for the consumer market.

PMID- 20032977
TI  - Resistance is futile.

PMID- 20032978
TI  - Images and icons.

PMID- 20032975
TI  - The transcriptional network for mesenchymal transformation of brain tumours.
AB  - The inference of transcriptional networks that regulate transitions into
      physiological or pathological cellular states remains a central challenge in
      systems biology. A mesenchymal phenotype is the hallmark of tumour aggressiveness
      in human malignant glioma, but the regulatory programs responsible for
      implementing the associated molecular signature are largely unknown. Here we show
      that reverse-engineering and an unbiased interrogation of a glioma-specific
      regulatory network reveal the transcriptional module that activates expression of
      mesenchymal genes in malignant glioma. Two transcription factors (C/EBPbeta and
      STAT3) emerge as synergistic initiators and master regulators of mesenchymal
      transformation. Ectopic co-expression of C/EBPbeta and STAT3 reprograms neural
      stem cells along the aberrant mesenchymal lineage, whereas elimination of the two
      factors in glioma cells leads to collapse of the mesenchymal signature and
      reduces tumour aggressiveness. In human glioma, expression of C/EBPbeta and STAT3
      correlates with mesenchymal differentiation and predicts poor clinical outcome.
      These results show that the activation of a small regulatory module is necessary
      and sufficient to initiate and maintain an aberrant phenotypic state in cancer
      cells.

PMID- 20032979
TI  - A golden opportunity.

PMID- 20032981
TI  - Nanomedicine: barcodes check out prostate cancer.

PMID- 20032982
TI  - Photonic-plasmonic devices: a 7-nm light pen makes its mark.

PMID- 20032983
TI  - Quantum devices: towards entangled electrons.

PMID- 20032985
TI  - Oxide materials: superconductivity on the other side.

PMID- 20032987
TI  - Effects of Bryonia laciniosa seeds on sexual behaviour of male rats.
AB  - Ethanolic extract of seeds of Bryonia laciniosa Linn was administered orally to
      groups of male albino rats at the dose levels of 50, 100, and 150 mg kg(-1) body
      weight per day for 28 days. The changes in sexual behaviour, reproductive organ
      weights, histology of testis and epididymis, epididymal sperm density, and
      androgenic hormone levels were evaluated. The sexual behaviour parameters studied
      such as mount frequency, intromission frequency, mount latency, intromission
      latency were significantly affected. Increase in body weight as well as weight of
      testis, prostate, seminal vesicle, and epididymis was noticed. Transverse
      sections of testis exhibited increased spermatogenesis and a significant increase
      in sperm count in epididymis. The fructose content of seminal vesicle was also
      increased. The extract treatment also brought a significant increase in serum
      testosterone and luteinizing hormone levels. The studies clearly reflect
      androgenic activity of the extract and its effects on hypothalamic pituitary
      gonadal axis.

PMID- 20032988
TI  - The endothelial cell in health and disease: its function, dysfunction,
      measurement and therapy.
AB  - Endothelial cells have numerous endocrine functions and contribute to a variety
      of processes, including penile erection and vasodilation. Endothelial dysfunction
      is associated with cardiovascular risk factors and has been implicated in the
      pathogenesis of atherosclerosis and ED. This study reviews endothelial function,
      in addition to endothelial dysfunction and its role in atherosclerosis and ED.
      Measurement of endothelial function is reviewed, including catheter-based
      methods, venous occlusion plethysmography, high-frequency ultrasound, peripheral
      arterial tonometry, digital pulse amplitude tonometry, digital thermal
      monitoring, the L-arginine test and measurement of compounds released by
      endothelial cells. Therapy and medications that improve endothelial function are
      reviewed. As the scientific community learns more about the importance of the
      endothelium, it is increasingly important for the clinician to understand
      endothelial function, dysfunction, measurement of endothelial function and
      therapies that affect this remarkable cell type.

PMID- 20032986
TI  - Properties and emerging applications of self-assembled structures made from
      inorganic nanoparticles.
AB  - Just as nanoparticles display properties that differ from those of bulk samples
      of the same material, ensembles of nanoparticles can have collective properties
      that are different to those displayed by individual nanoparticles and bulk
      samples. Self-assembly has emerged as a powerful technique for controlling the
      structure and properties of ensembles of inorganic nanoparticles. Here we review
      different strategies for nanoparticle self-assembly, the properties of self
      assembled structures of nanoparticles, and potential applications of such
      structures. Many of these properties and possible applications rely on our
      ability to control the interactions between the electronic, magnetic and optical
      properties of the individual nanoparticles.

PMID- 20032989
TI  - Health-related quality of life assessment in dermatology: interpretation of
      Skindex-29 scores using patient-based anchors.
AB  - In dermatology, the clinical use of health-related quality of life (HRQL) scores
      is impeded by lack of empirically and clinically based interpretation of these
      scores. We aimed to facilitate the interpretation of Skindex-29 domain and
      overall scores by identifying clinically meaningful cut-off scores, using patient
      based anchors. Consecutively included dermatology outpatients completed the
      Skindex-29 and four sets of anchor-based questions, such as questions on the
      impact of skin disease on HRQL, on global disease severity, and on psychiatric
      morbidity. Pearson's correlations and receiver operating characteristic analysis
      were used to identify the optimal Skindex-29 cut-off scores corresponding to
      severely impaired HRQL. A total of 339/434 patients completed the questionnaires
      (response rate 78%), of which 322 could be used for data analysis. Cut-off scores
      associated with the patient-based anchors on the impact of skin disease on HRQL
      showed the highest accuracy (area under the curve ranged from 0.83 to 0.91). The
      corresponding Skindex-29 cut-off scores for severely impaired HRQL were as
      follows: > or =52 points on symptoms, > or =39 on emotions, > or =37 on
      functioning, and > or =44 on the overall score. The estimated cut-off scores can
      be used in clinical practice to identify patients with (very) severely impaired
      HRQL.

PMID- 20032991
TI  - Effects of the aminophenol analogue p-Dodecylaminophenol on mouse skin.
AB  - p-Dodecylaminophenol (p-DDAP) was designed on the basis of structure-activity
      relationship studies on N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR), a
      synthetic derivative of retinoic acid (RA). p-DDAP exhibits antioxidative
      activities greater than those of RA and 4-HPR. RA shows biological effects in
      epidermal cells that include the inhibition of differentiation to the squamous
      phenotype. In the current study, we examined the effects of topical p-DDAP
      treatment on the skin of hairless mice as compared with those of RA treatment. p
      DDAP caused an increase in epidermal thickness and decreased matrix
      metalloprotease and hyaluronidase activities in mouse skin tissues to the same
      extent that RA did. p-DDAP did not induce desquamation, erythema, or inflammatory
      cytokine expression as observed with RA treatment. Two-dimensional polyacrylamide
      gel electrophoresis patterns of proteins from skin treated with p-DDAP were
      distinct from those treated with RA. A protein induced by both p-DDAP and RA was
      identified as cytokeratin 16. p-DDAP did not elevate transcriptional activities
      of RA nuclear receptors. These results suggest that p-DDAP improves skin as
      potently as RA without causing the desquamation and erythema that the latter
      does. An increase in cytokeratin 16 expression might be essential for the effects
      of both p-DDAP and RA in skin healing and maintenance.

PMID- 20032990
TI  - Pseudoxanthoma elasticum: molecular genetics and putative pathomechanisms.
AB  - Pseudoxanthoma elasticum (PXE), a prototypic heritable disorder with ectopic
      mineralization, manifests with characteristic skin findings, ocular involvement
      and cardiovascular problems, with considerable morbidity and mortality. The
      classic forms of PXE are due to loss-of-function mutations in the ABCC6 gene,
      which encodes ABCC6, a transmembrane efflux transporter expressed primarily in
      the liver. Several lines of evidence suggest that PXE is a primary metabolic
      disorder, which in the absence of ABCC6 transporter activity, displays reduced
      plasma anti-mineralization capacity due to reduced fetuin-A and matrix gla
      protein (MGP) levels. MGP requires to be activated by gamma-glutamyl
      carboxylation, a vitamin K-dependent reaction, to serve in an anti-mineralization
      role in the peripheral connective tissue cells. Although the molecules
      transported from the hepatocytes to circulation by ABCC6 in vivo remain
      unidentified, it has been hypothesized that a critical vitamin K derivative, such
      as reduced vitamin K conjugated with glutathione, is secreted to circulation
      physiologically, but not in the absence of ABCC6 transporter activity. As a
      result, activation of MGP by gamma-glutamyl carboxylase is diminished, allowing
      slow yet progressive mineralization of connective tissues characteristic of PXE.
      Understanding of the pathomechanistic details of PXE provides a basis for the
      development of targeted molecular therapies for this currently intractable
      disease.

PMID- 20032992
TI  - Sebum free fatty acids enhance the innate immune defense of human sebocytes by
      upregulating beta-defensin-2 expression.
AB  - Various sebum free fatty acids (FFAs) have shown antibacterial activity against a
      broad range of gram-positive bacteria, resulting in the suggestion that they are
      accountable, at least partially, for the direct antimicrobial activity of the
      skin surface. In this study, we examined the effects of sebum FFAs on the
      antimicrobial peptide (AMP)-mediated innate immune defense of human sebocytes.
      Incubation of lauric acid, palmitic acid, or oleic acid (OA) with human sebocytes
      dramatically enhanced their expression of human beta-defensin (hBD)-2, one of the
      predominant AMPs found in the skin, whereas remarkable increases in hBD-1, hBD-3,
      and human cathelicidin LL-37 were not observed. Secreted hBD-2 was detectable by
      western blotting in the supernatant of sebocyte culture incubated with each FFA,
      but not with a vehicle control. The supernatant of FFA-incubated sebocyte culture
      showed antimicrobial activity against Propionibacterium acnes, whereas the
      enhanced antimicrobial activity of human sebocytes was neutralized by anti-hBD-2
      IgG. In addition, the FFA-induced hBD-2 expression was suppressed by blocking the
      cluster of differentiation (CD)36 fatty acid translocase on the surface of
      sebocytes with anti-human CD36 IgG or blocking the NF-kappaB signaling pathway
      with BMS-345541, a highly selective inhibitor of inhibitory kappaB kinase. These
      data suggest that sebum FFAs upregulate the expression of hBD-2 in human
      sebocytes, which may enhance the disinfecting activity of the human sebaceous
      gland. The FFA-induced upregulation of hBD-2 is facilitated by CD36-mediated FFA
      uptake and NF-kappaB-mediated transactivation. The upregulation of mouse beta
      defensin 4, a mouse ortholog for hBD-2, was also observed in the hair follicle
      sebaceous glands of mouse ear skin after an epicutaneous application of OA, the
      most hBD-2-inducible FFA tested. This report highlights the potential of using
      FFAs as a multifunctional antimicrobial therapy agent for acne vulgaris
      treatment; FFAs may provide direct antibacterial activities against P. acnes and
      enhance the skin's innate antibacterial defense by inducing the expression of hBD
      2 in sebocytes as well.

PMID- 20032997
TI  - After Copenhagen.

PMID- 20032994
TI  - Enhanced lesional Foxp3 expression and peripheral anergic lymphocytes indicate a
      role for regulatory T cells in Indian post-kala-azar dermal leishmaniasis.
AB  - Indian post-kala-azar dermal leishmaniasis (PKDL) is a low-frequency (5-10%)
      dermal sequela of visceral leishmaniasis (VL) caused by Leishmania donovani;
      importantly, affected individuals are speculated to be parasite reservoirs.
      Insight into its immunopathogenesis could translate into rational
      immunomodulatory therapeutic approaches against leishmaniases. In patients with
      PKDL (n=21), peripheral lymphocytes were analyzed for surface markers,
      intracellular cytokines, and lymphoproliferative responses using flow cytometry.
      In lesional tissue biopsies (n=12), expression of counter-regulatory cytokines
      (IFN-gamma and IL-10) and the T-regulatory transcription factor forkhead box
      protein 3 (Foxp3) was analyzed using reverse transcriptase-PCR, along with
      immunohistochemical detection (n=8) of CD3 and Foxp3 positivity. In patients with
      PKDL, circulating CD8(+)CD28(-) and antigen-induced IL-10(+)CD3(+) lymphocytes
      were increased and receded with treatment. CD8(+) lymphocytes showed impaired
      proliferative responses to L. donovani antigen (LDA) and phytohemagglutinin,
      which were reinstated after treatment. At presentation, the upregulated lesional
      IFN-gamma and IL-10 messenger RNA (mRNA), Foxp3 mRNA, and protein were curtailed
      after treatment. In Indian patients with PKDL, increased frequency of the
      CD8(+)CD28(-) phenotype, enhanced antigen-specific IL-10 production, and
      accompanying anergy of circulating lymphocytes suggest their regulatory nature.
      Furthermore, the concomitantly elevated lesional expression of Foxp3 suggests
      their possible recruitment into the lesional site, which would sustain disease
      pathology.

PMID- 20032993
TI  - Circulating Th17, Th22, and Th1 cells are increased in psoriasis.
AB  - Th17, Th22, and Th1 cells are detected in psoriatic skin lesions and implicated
      in psoriasis pathogenesis, but inflammatory T cell numbers in blood, as well as
      the relative importance of each cell type, is unclear. Using 7-color flow
      cytometry, circulating Th17, Th22, and Th1 cells were quantified in 21 untreated
      psoriatics and 17 healthy individuals. CCR6 was the best cell surface marker for
      IL-17A+ cells when compared with IL-23R or CD161. CCR6+, IL-17A+, IL-22+, CCR6+IL
      17A+, CCR6+IL-22+, CCR6+tumor necrosis factor-alpha+, IL-17A+IFN-gamma-, IL
      17A+IL-22+IFN-gamma-, and IL-17A+IL-22-IFN-gamma- cells were increased in
      psoriatics (all values P<0.001), indicating elevations in circulating Th17 cells,
      using multiple criteria to define these cells. Th22 (IL-17A-IL-22+IFN-gamma-,
      P<0.05) and Th1 (IL-17A-IFN-gamma+, P<0.05) cells were also increased in
      psoriatics, but to a lesser extent. Inhibition of either NF-kappaB or STAT3 in
      vitro blocked cytokine production by both Th17 and Th1 cells. Circulating levels
      of Th17 and Th1 cells decreased in a subset of five psoriasis patients serially
      evaluated following induction therapy with infliximab. In summary, elevated
      numbers of circulating inflammatory T cells may contribute to cutaneous
      inflammation and systemic inflammatory disease that occurs in individuals with
      psoriasis.

PMID- 20033008
TI  - News 2009.

PMID- 20033010
TI  - World looks ahead post-Copenhagen.

PMID- 20033011
TI  - 'Dark-matter' events spotted.

PMID- 20033012
TI  - Tsunami watch.

PMID- 20033013
TI  - Extortion attempt involved retracted papers.

PMID- 20033014
TI  - Fraud rocks protein community.

PMID- 20033015
TI  - 2009 Gallery: Images of the year.

PMID- 20033016
TI  - Newsmaker of the year: The power player.

PMID- 20033017
TI  - Don't forget the artists when studying perception of art.

PMID- 20033018
TI  - Global Darwin: ideas blurred in early eastern translations.

PMID- 20033019
TI  - How much are we willing to pay for a fossil?

PMID- 20033020
TI  - Global Darwin: long kept under wraps in Pakistan.

PMID- 20033021
TI  - Goodbye to Darwin from a contemporary with vision.

PMID- 20033022
TI  - A toast to Mendeleev, who merits more than periodic honour.

PMID- 20033024
TI  - 'Snow joke as festive season gives rise to a blizzard of fake flakes.

PMID- 20033023
TI  - Rewilding can cause rather than solve ecological problems.

PMID- 20033029
TI  - Applied physics: Bubbly but quiet.

PMID- 20033030
TI  - Astrophysics: Stellar revival in old clusters.

PMID- 20033028
TI  - Ageing: Diet and longevity in the balance.

PMID- 20033032
TI  - Hangovers: Uncongenial congeners.

PMID- 20033031
TI  - Structural biology: Translocation chamber's secrets.

PMID- 20033033
TI  - Nanotechnology: Molecular transistors scrutinized.

PMID- 20033036
TI  - Obituary: Vitaly Ginzburg (1916-2009).

PMID- 20033037
TI  - The first decade of science with Chandra and XMM-Newton.
AB  - NASA's Chandra X-ray Observatory and the ESA's X-ray Multi-Mirror Mission (XMM
      Newton) made their first observations ten years ago. The complementary
      capabilities of these observatories allow us to make high-resolution images and
      precisely measure the energy of cosmic X-rays. Less than 50 years after the first
      detection of an extrasolar X-ray source, these observatories have achieved an
      increase in sensitivity comparable to going from naked-eye observations to the
      most powerful optical telescopes over the past 400 years. We highlight some of
      the many discoveries made by Chandra and XMM-Newton that have transformed twenty
      first century astronomy.

PMID- 20033038
TI  - Complex landscapes of somatic rearrangement in human breast cancer genomes.
AB  - Multiple somatic rearrangements are often found in cancer genomes; however, the
      underlying processes of rearrangement and their contribution to cancer
      development are poorly characterized. Here we use a paired-end sequencing
      strategy to identify somatic rearrangements in breast cancer genomes. There are
      more rearrangements in some breast cancers than previously appreciated.
      Rearrangements are more frequent over gene footprints and most are
      intrachromosomal. Multiple rearrangement architectures are present, but tandem
      duplications are particularly common in some cancers, perhaps reflecting a
      specific defect in DNA maintenance. Short overlapping sequences at most
      rearrangement junctions indicate that these have been mediated by non-homologous
      end-joining DNA repair, although varying sequence patterns indicate that multiple
      processes of this type are operative. Several expressed in-frame fusion genes
      were identified but none was recurrent. The study provides a new perspective on
      cancer genomes, highlighting the diversity of somatic rearrangements and their
      potential contribution to cancer development.

PMID- 20033039
TI  - The chromatin remodeller ACF acts as a dimeric motor to space nucleosomes.
AB  - Evenly spaced nucleosomes directly correlate with condensed chromatin and gene
      silencing. The ATP-dependent chromatin assembly factor (ACF) forms such
      structures in vitro and is required for silencing in vivo. ACF generates and
      maintains nucleosome spacing by constantly moving a nucleosome towards the longer
      flanking DNA faster than the shorter flanking DNA. How the enzyme rapidly moves
      back and forth between both sides of a nucleosome to accomplish bidirectional
      movement is unknown. Here we show that nucleosome movement depends cooperatively
      on two ACF molecules, indicating that ACF functions as a dimer of ATPases.
      Further, the nucleotide state determines whether the dimer closely engages one or
      both sides of the nucleosome. Three-dimensional reconstruction by single-particle
      electron microscopy of the ATPase-nucleosome complex in an activated ATP state
      reveals a dimer architecture in which the two ATPases face each other. Our
      results indicate a model in which the two ATPases work in a coordinated manner,
      taking turns to engage either side of a nucleosome, thereby allowing processive
      bidirectional movement. This novel dimeric motor mechanism differs from that of
      dimeric motors such as kinesin and dimeric helicases that processively
      translocate unidirectionally and reflects the unique challenges faced by motors
      that move nucleosomes.

PMID- 20033040
TI  - Dynamics of nucleosome remodelling by individual ACF complexes.
AB  - The ATP-dependent chromatin assembly and remodelling factor (ACF) functions to
      generate regularly spaced nucleosomes, which are required for heritable gene
      silencing. The mechanism by which ACF mobilizes nucleosomes remains poorly
      understood. Here we report a single-molecule FRET study that monitors the
      remodelling of individual nucleosomes by ACF in real time, revealing previously
      unknown remodelling intermediates and dynamics. In the presence of ACF and ATP,
      the nucleosomes exhibit gradual translocation along DNA interrupted by well
      defined kinetic pauses that occurred after approximately seven or three to four
      base pairs of translocation. The binding of ACF, translocation of DNA and exiting
      of translocation pauses are all ATP-dependent, revealing three distinct
      functional roles of ATP during remodelling. At equilibrium, a continuously bound
      ACF complex can move the nucleosome back-and-forth many times before
      dissociation, indicating that ACF is a highly processive and bidirectional
      nucleosome translocase.

PMID- 20033041
TI  - Two distinct sequences of blue straggler stars in the globular cluster M 30.
AB  - Stars in globular clusters are generally believed to have all formed at the same
      time, early in the Galaxy's history. 'Blue stragglers' are stars massive enough
      that they should have evolved into white dwarfs long ago. Two possible mechanisms
      have been proposed for their formation: mass transfer between binary companions
      and stellar mergers resulting from direct collisions between two stars. Recently
      the binary explanation was claimed to be dominant. Here we report that there are
      two distinct parallel sequences of blue stragglers in M 30. This globular cluster
      is thought to have undergone 'core collapse', during which both the collision
      rate and the mass transfer activity in binary systems would have been enhanced.
      We suggest that the two observed sequences are a consequence of cluster core
      collapse, with the bluer population arising from direct stellar collisions and
      the redder one arising from the evolution of close binaries that are probably
      still experiencing an active phase of mass transfer.

PMID- 20033042
TI  - A binary star fraction of 76 per cent and unusual orbit parameters for the blue
      stragglers of NGC 188.
AB  - Blue straggler stars lie on or near the main sequences of star clusters (all
      members of which formed around the same time), but typically are more luminous
      than the turn-off stars and therefore long ago should have evolved off the main
      sequence to become giants and white dwarfs. They are thought to derive from
      normal main-sequence stars that have undergone a recent increase in mass.
      Statistical evidence indicates that in globular star clusters the blue stragglers
      probably form from binary stars. The specific formation processes, such as mass
      transfer, mergers or stellar collisions during dynamical encounters of binary
      stars, remain unresolved. Here we report that 16 of the 21 blue stragglers (76
      per cent) in the old (7-Gyr; ref. 2) open cluster NGC 188 are currently in binary
      systems, a frequency three times that found among normal solar-type main-sequence
      stars. These blue straggler binaries have a remarkable period-eccentricity
      distribution, with all but three having orbital periods of approximately 1,000
      days. Moreover, these stars are rotating faster than normal main-sequence stars
      of the same surface temperatures. These data show that most, and possibly all,
      blue stragglers derive from multiple-star systems, and indicate that the several
      formation processes operate simultaneously. We suggest that rapid rotation of
      blue stragglers may place upper limits on their ages.

PMID- 20033043
TI  - A strong, highly-tilted interstellar magnetic field near the Solar System.
AB  - Magnetic fields play an important (sometimes dominant) role in the evolution of
      gas clouds in the Galaxy, but the strength and orientation of the field in the
      interstellar medium near the heliosphere has been poorly constrained. Previous
      estimates of the field strength range from 1.8-2.5 microG and the field was
      thought to be parallel to the Galactic plane or inclined by 38-60 degrees (ref.
      2) or 60-90 degrees (ref. 3) to this plane. These estimates relied either on
      indirect observational inferences or modelling in which the interstellar neutral
      hydrogen was not taken into account. Here we report measurements of the
      deflection of the solar wind plasma flows in the heliosheath to determine the
      magnetic field strength and orientation in the interstellar medium. We find that
      the field strength in the local interstellar medium is 3.7-5.5 microG. The field
      is tilted approximately 20-30 degrees from the interstellar medium flow direction
      (resulting from the peculiar motion of the Sun in the Galaxy) and is at an angle
      of about 30 degrees from the Galactic plane. We conclude that the interstellar
      medium field is turbulent or has a distortion in the solar vicinity.

PMID- 20033044
TI  - Observation of molecular orbital gating.
AB  - The control of charge transport in an active electronic device depends intimately
      on the modulation of the internal charge density by an external node. For
      example, a field-effect transistor relies on the gated electrostatic modulation
      of the channel charge produced by changing the relative position of the
      conduction and valence bands with respect to the electrodes. In molecular-scale
      devices, a longstanding challenge has been to create a true three-terminal device
      that operates in this manner (that is, by modifying orbital energy). Here we
      report the observation of such a solid-state molecular device, in which transport
      current is directly modulated by an external gate voltage. Resonance-enhanced
      coupling to the nearest molecular orbital is revealed by electron tunnelling
      spectroscopy, demonstrating direct molecular orbital gating in an electronic
      device. Our findings demonstrate that true molecular transistors can be created,
      and so enhance the prospects for molecularly engineered electronic devices.

PMID- 20033045
TI  - Glaciers as a source of ancient and labile organic matter to the marine
      environment.
AB  - Riverine organic matter supports of the order of one-fifth of estuarine
      metabolism. Coastal ecosystems are therefore sensitive to alteration of both the
      quantity and lability of terrigenous dissolved organic matter (DOM) delivered by
      rivers. The lability of DOM is thought to vary with age, with younger, relatively
      unaltered organic matter being more easily metabolized by aquatic heterotrophs
      than older, heavily modified material. This view is developed exclusively from
      work in watersheds where terrestrial plant and soil sources dominate streamwater
      DOM. Here we characterize streamwater DOM from 11 coastal watersheds on the Gulf
      of Alaska that vary widely in glacier coverage (0-64 per cent). In contrast to
      non-glacial rivers, we find that the bioavailability of DOM to marine
      microorganisms is significantly correlated with increasing (14)C age. Moreover,
      the most heavily glaciated watersheds are the source of the oldest (
      approximately 4 kyr (14)C age) and most labile (66 per cent bioavailable) DOM.
      These glacial watersheds have extreme runoff rates, in part because they are
      subject to some of the highest rates of glacier volume loss on Earth. We estimate
      the cumulative flux of dissolved organic carbon derived from glaciers
      contributing runoff to the Gulf of Alaska at 0.13 +/- 0.01 Tg yr(-1) (1 Tg =
      10(12) g), of which approximately 0.10 Tg is highly labile. This indicates that
      glacial runoff is a quantitatively important source of labile reduced carbon to
      marine ecosystems. Moreover, because glaciers and ice sheets represent the second
      largest reservoir of water in the global hydrologic system, our findings indicate
      that climatically driven changes in glacier volume could alter the age, quantity
      and reactivity of DOM entering coastal oceans.

PMID- 20033046
TI  - Tremor-tide correlations and near-lithostatic pore pressure on the deep San
      Andreas fault.
AB  - Since its initial discovery nearly a decade ago, non-volcanic tremor has provided
      information about a region of the Earth that was previously thought incapable of
      generating seismic radiation. A thorough explanation of the geologic process
      responsible for tremor generation has, however, yet to be determined. Owing to
      their location at the plate interface, temporal correlation with geodetically
      measured slow-slip events and dominant shear wave energy, tremor observations in
      southwest Japan have been interpreted as a superposition of many low-frequency
      earthquakes that represent slip on a fault surface. Fluids may also be
      fundamental to the failure process in subduction zone environments, as
      teleseismic and tidal modulation of tremor in Cascadia and Japan and high Poisson
      ratios in both source regions are indicative of pressurized pore fluids. Here we
      identify a robust correlation between extremely small, tidally induced shear
      stress parallel to the San Andreas fault and non-volcanic tremor activity near
      Parkfield, California. We suggest that this tremor represents shear failure on a
      critically stressed fault in the presence of near-lithostatic pore pressure.
      There are a number of similarities between tremor in subduction zone
      environments, such as Cascadia and Japan, and tremor on the deep San Andreas
      transform, suggesting that the results presented here may also be applicable in
      other tectonic settings.

PMID- 20033047
TI  - The velocity of climate change.
AB  - The ranges of plants and animals are moving in response to recent changes in
      climate. As temperatures rise, ecosystems with 'nowhere to go', such as
      mountains, are considered to be more threatened. However, species survival may
      depend as much on keeping pace with moving climates as the climate's ultimate
      persistence. Here we present a new index of the velocity of temperature change
      (km yr(-1)), derived from spatial gradients ( degrees C km(-1)) and multimodel
      ensemble forecasts of rates of temperature increase ( degrees C yr(-1)) in the
      twenty-first century. This index represents the instantaneous local velocity
      along Earth's surface needed to maintain constant temperatures, and has a global
      mean of 0.42 km yr(-1) (A1B emission scenario). Owing to topographic effects, the
      velocity of temperature change is lowest in mountainous biomes such as tropical
      and subtropical coniferous forests (0.08 km yr(-1)), temperate coniferous forest,
      and montane grasslands. Velocities are highest in flooded grasslands (1.26 km yr(
      1)), mangroves and deserts. High velocities suggest that the climates of only 8%
      of global protected areas have residence times exceeding 100 years. Small
      protected areas exacerbate the problem in Mediterranean-type and temperate
      coniferous forest biomes. Large protected areas may mitigate the problem in
      desert biomes. These results indicate management strategies for minimizing
      biodiversity loss from climate change. Montane landscapes may effectively shelter
      many species into the next century. Elsewhere, reduced emissions, a much expanded
      network of protected areas, or efforts to increase species movement may be
      necessary.

PMID- 20033051
TI  - Changing paradigms in the treatment of chronic lymphocytic leukemia.
AB  - Progress in our understanding of chronic lymphocytic leukemia and its treatment
      has resulted in a more tailored approach to patient management, with different
      therapeutic regimens for different patient populations. The current standard of
      care has evolved from single-agent therapy with chlorambucil or cyclophosphamide,
      through the introduction of purine analogs to the more recent introduction of
      chemoimmunotherapy. Selection of appropriate initial therapy should be based
      primarily on patient characteristics such as age, performance status and the
      expected clinical course of the leukemia based on established risk factors.
      Achieving a complete and durable response is the major goal for fit patients;
      chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab would be
      advantageous. Alternatively, in unfit patients, controlling symptoms is the
      essential treatment goal and a regimen with a more favorable toxicity profile
      should be applied. This manuscript reviews the data that has lead to current
      treatment choices, advises on tailored therapies and discusses emerging trends.
      Data for this review was identified by a search of electronic information
      including Medline and PubMed databases, conference proceedings and trial
      registers. Critical analysis of extracted data was undertaken with attention to
      trial phase, treatment schedules and end points, including response rates, follow
      up times, progression-free survival and overall survival.

PMID- 20033049
TI  - Novel mutant-selective EGFR kinase inhibitors against EGFR T790M.
AB  - The clinical efficacy of epidermal growth factor receptor (EGFR) kinase
      inhibitors in EGFR-mutant non-small-cell lung cancer (NSCLC) is limited by the
      development of drug-resistance mutations, including the gatekeeper T790M
      mutation. Strategies targeting EGFR T790M with irreversible inhibitors have had
      limited success and are associated with toxicity due to concurrent inhibition of
      wild-type EGFR. All current EGFR inhibitors possess a structurally related
      quinazoline-based core scaffold and were identified as ATP-competitive inhibitors
      of wild-type EGFR. Here we identify a covalent pyrimidine EGFR inhibitor by
      screening an irreversible kinase inhibitor library specifically against EGFR
      T790M. These agents are 30- to 100-fold more potent against EGFR T790M, and up to
      100-fold less potent against wild-type EGFR, than quinazoline-based EGFR
      inhibitors in vitro. They are also effective in murine models of lung cancer
      driven by EGFR T790M. Co-crystallization studies reveal a structural basis for
      the increased potency and mutant selectivity of these agents. These mutant
      selective irreversible EGFR kinase inhibitors may be clinically more effective
      and better tolerated than quinazoline-based inhibitors. Our findings demonstrate
      that functional pharmacological screens against clinically important mutant
      kinases represent a powerful strategy to identify new classes of mutant-selective
      kinase inhibitors.

PMID- 20033048
TI  - A phylogeny-driven genomic encyclopaedia of Bacteria and Archaea.
AB  - Sequencing of bacterial and archaeal genomes has revolutionized our understanding
      of the many roles played by microorganisms. There are now nearly 1,000 completed
      bacterial and archaeal genomes available, most of which were chosen for
      sequencing on the basis of their physiology. As a result, the perspective
      provided by the currently available genomes is limited by a highly biased
      phylogenetic distribution. To explore the value added by choosing microbial
      genomes for sequencing on the basis of their evolutionary relationships, we have
      sequenced and analysed the genomes of 56 culturable species of Bacteria and
      Archaea selected to maximize phylogenetic coverage. Analysis of these genomes
      demonstrated pronounced benefits (compared to an equivalent set of genomes
      randomly selected from the existing database) in diverse areas including the
      reconstruction of phylogenetic history, the discovery of new protein families and
      biological properties, and the prediction of functions for known genes from other
      organisms. Our results strongly support the need for systematic 'phylogenomic'
      efforts to compile a phylogeny-driven 'Genomic Encyclopedia of Bacteria and
      Archaea' in order to derive maximum knowledge from existing microbial genome data
      as well as from genome sequences to come.

PMID- 20033054
TI  - Standardized MRD quantification in European ALL trials: proceedings of the Second
      International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008.
AB  - Assessment of minimal residual disease (MRD) has acquired a prominent position in
      European treatment protocols for patients with acute lymphoblastic leukemia
      (ALL), on the basis of its high prognostic value for predicting outcome and the
      possibilities for implementation of MRD diagnostics in treatment stratification.
      Therefore, there is an increasing need for standardization of methodologies and
      harmonization of terminology. For this purpose, a panel of representatives of all
      major European study groups on childhood and adult ALL and of international
      experts on PCR- and flow cytometry-based MRD assessment was built in the context
      of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20
      September 2008. The panel summarized the current state of MRD diagnostics in ALL
      and developed recommendations on the minimal technical requirements that should
      be fulfilled before implementation of MRD diagnostics into clinical trials.
      Finally, a common terminology for a standard description of MRD response and
      monitoring was established defining the terms 'complete MRD response', 'MRD
      persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a
      refined and standardized assessment of response to treatment in adult and
      childhood ALL, and provides a sound basis for the comparison of MRD results
      between different treatment protocols.

PMID- 20033053
TI  - Mobilization studies in complement-deficient mice reveal that optimal AMD3100
      mobilization of hematopoietic stem cells depends on complement cascade activation
      by AMD3100-stimulated granulocytes.
AB  - We reported that complement cascade (CC) becomes activated in bone marrow (BM)
      during mobilization of hematopoietic stem/progenitor cells (HSPCs) induced by
      granulocyte colony-stimulating factor (G-CSF) and C5 cleavage has an important
      function in optimal egress of HSPCs. In this work, we explored whether CC is
      involved in mobilization of HSPCs induced by the CXCR4 antagonist, AMD3100. To
      address this question, we performed mobilization studies in mice that display a
      defect in the activation of the proximal steps of CC (Rag(-/-), severe combined
      immune deficient (SCID), C2.Cfb(-/-)) as well as in mice that do not activate the
      distal steps of CC (C5(-/-)). We noticed that proximal CC activation-deficient
      mice (above C5 level), in contrast to distal step CC activation-deficient C5(-/-)
      ones, mobilize normally in response to AMD3100 administration. We hypothesized
      that this discrepancy in mobilization could be explained by AMD3100-activating C5
      in Rag(-/-), SCID, and C2.Cfb(-/-) animals in a non-canonical mechanism involving
      activated granulocytes. To support this, granulocytes (i) first egress from BM
      and (ii) secrete several proteases that cleave/activate C5 in response to
      AMD3100. We conclude that AMD3100-directed mobilization of HSPCs, similarly to G
      CSF-induced mobilization, depends on activation of CC; however, in contrast to G
      CSF, AMD3100 activates the distal steps of CC directly at the C5 level. Overall,
      these data support that C5 cleavage fragments and distal steps of CC activation
      are required for optimal mobilization of HSPCs.

PMID- 20033052
TI  - Long-term results of Tokyo Children's Cancer Study Group trials for childhood
      acute lymphoblastic leukemia, 1984-1999.
AB  - We report the long-term results of Tokyo Children's Cancer Study Group's studies
      L84-11, L89-12, L92-13, and L95-14 for 1846 children with acute lymphoblastic
      leukemia, which were conducted between 1984 and 1999. The value of event-free
      survival (EFS)+/-s.e. was 67.2+/-2.2% at 10 years in L84-11, which was not
      improved in the following two studies, and eventually improved to 75.0+/-1.8% at
      10 years in L95-14 study. The lower EFS of the L89-12 reflected a high rate of
      induction failure because of infection and delayed remission in very high-risk
      patients. The L92-13 study was characterized by short maintenance therapy; it
      resulted in poor EFS, particularly in the standard-risk (SR) group and boys.
      Females did significantly better than males in EFS in the early three studies.
      The gender difference was not significant in overall survival, partly because
      >60% of the males survived after the testicular relapse. Randomized studies in
      the former three protocols revealed that intermediate- or high-dose methotrexate
      therapy significantly reduced the testicular relapse rate. In the L95-14 study,
      gender difference disappeared in EFS. Contrary to the results of larger-scale
      studies, the randomized control study in the L95-14 reconfirmed with updated data
      that dexamethasone 8 mg/m(2) had no advantage over prednisolone 60 mg/m(2) in the
      SR and intermediate-risk groups. Prophylactic cranial irradiation was assigned to
      100, 80, 44, and 44% of the patients in the studies, respectively. Isolated
      central nervous system relapse rates decreased to <2% in the last two trials.
      Secondary brain tumors developed in 12 patients at 8-22 years after cranial
      irradiation. Improvement of the remission induction rates and the complete
      omission of irradiation are currently main objectives in our studies.

PMID- 20033055
TI  - CD3+/CD19+-depleted grafts in HLA-matched allogeneic peripheral blood stem cell
      transplantation lead to early NK cell cytolytic responses and reduced inhibitory
      activity of NKG2A.
AB  - Natural killer (NK) cells have an important function in the anti-tumor response
      early after stem cell transplantation (SCT). As part of a prospective randomized
      phase III study, directly comparing the use of CD3(+)/CD19(+)-depleted peripheral
      blood stem cell (PBSC) harvests with CD34(+)-selected PBSC harvests in allogeneic
      human leukocyte antigen-matched SCT, we here show that the use of CD3(+)/CD19(+)
      depleted PBSC grafts leads to early NK cell repopulation and reconstitution of
      the CD56(dim) and CD56(bright) NK cell subsets, with concomitant high cytolytic
      capacity. In the CD34 group, this process took significantly longer. Moreover, in
      the CD3/19 group after reconstitution, a higher percentage of killer
      immunoglobulin-like receptor-positive NK cells was found. Although similar
      percentages of CD94-positive NK cells were found in both groups, in the CD34
      group, almost all expressed the inhibitory CD94:NKG2A complex, whereas in the
      CD3/19 group, the inhibitory CD94:NKG2A and the activating CD94:NKG2C complex
      were equally distributed. This preferential development of NKG2C-expressing NK
      cells in the CD3/19 group was paralleled by a loss of NKG2A-mediated inhibition
      of NK cell degranulation. These results show that the use of CD3(+)/CD19(+)
      depleted grafts facilitates strong NK cell cytolytic responses directly after
      SCT, and the rapid emergence of an NK cell receptor phenotype that is more prone
      to activation.

PMID- 20033056
TI  - Dasatinib promotes ATRA-induced differentiation of AML cells.

PMID- 20033057
TI  - Structure of an integrin with an alphaI domain, complement receptor type 4.
AB  - We report the structure of an integrin with an alphaI domain, alpha(X)beta(2),
      the complement receptor type 4. It was earlier expected that a fixed orientation
      between the alphaI domain and the beta-propeller domain in which it is inserted
      would be required for allosteric signal transmission. However, the alphaI domain
      is highly flexible, enabling two betaI domain conformational states to couple to
      three alphaI domain states, and greater accessibility for ligand recognition.
      Although alpha(X)beta(2) is bent similarly to integrins that lack alphaI domains,
      the terminal domains of the alpha- and beta-legs, calf-2 and beta-tail, are
      oriented differently than in alphaI-less integrins. Linkers extending to the
      transmembrane domains are unstructured. Previous mutations in the beta(2)-tail
      domain support the importance of extension, rather than a deadbolt, in integrin
      activation. The locations of further activating mutations and antibody epitopes
      show the critical role of extension, and conversion from the closed to the open
      headpiece conformation, in integrin activation. Differences among 10 molecules in
      crystal lattices provide unprecedented information on interdomain flexibility
      important for modelling integrin extension and activation.

PMID- 20033058
TI  - Fully efficient chromosome dimer resolution in Escherichia coli cells lacking the
      integral membrane domain of FtsK.
AB  - In bacteria, septum formation frequently initiates before the last steps of
      chromosome segregation. This is notably the case when chromosome dimers are
      formed by homologous recombination. Chromosome segregation then requires the
      activity of a double-stranded DNA transporter anchored at the septum by an
      integral membrane domain, FtsK. It was proposed that the transmembrane segments
      of proteins of the FtsK family form pores across lipid bilayers for the transport
      of DNA. Here, we show that truncated Escherichia coli FtsK proteins lacking all
      of the FtsK transmembrane segments allow for the efficient resolution of
      chromosome dimers if they are connected to a septal targeting peptide through a
      sufficiently long linker. These results indicate that FtsK does not need to
      transport DNA through a pore formed by its integral membrane domain. We propose
      therefore that FtsK transports DNA before membrane fusion, at a time when there
      is still an opening in the constricted septum.

PMID- 20033059
TI  - Structure of clathrin coat with bound Hsc70 and auxilin: mechanism of Hsc70
      facilitated disassembly.
AB  - The chaperone Hsc70 drives the clathrin assembly-disassembly cycle forward by
      stimulating dissociation of a clathrin lattice. A J-domain containing co
      chaperone, auxilin, associates with a freshly budded clathrin-coated vesicle, or
      with an in vitro assembled clathrin coat, and recruits Hsc70 to its specific
      heavy-chain-binding site. We have determined by electron cryomicroscopy (cryoEM),
      at about 11 A resolution, the structure of a clathrin coat (in the D6-barrel
      form) with specifically bound Hsc70 and auxilin. The Hsc70 binds a previously
      analysed site near the C-terminus of the heavy chain, with a stoichiometry of
      about one per three-fold vertex. Its binding is accompanied by a distortion of
      the clathrin lattice, detected by a change in the axial ratio of the D6 barrel.
      We propose that when Hsc70, recruited to a position close to its target by the
      auxilin J-domain, splits ATP, it clamps firmly onto its heavy-chain site and
      locks in place a transient fluctuation. Accumulation of the local strain thus
      imposed at multiple vertices can then lead to disassembly.

PMID- 20033060
TI  - DHPR alpha1S subunit controls skeletal muscle mass and morphogenesis.
AB  - The alpha1S subunit has a dual function in skeletal muscle: it forms the L-type
      Ca(2+) channel in T-tubules and is the voltage sensor of excitation-contraction
      coupling at the level of triads. It has been proposed that L-type Ca(2+) channels
      might also be voltage-gated sensors linked to transcriptional activity
      controlling differentiation. By using the U7-exon skipping strategy, we have
      achieved long-lasting downregulation of alpha1S in adult skeletal muscle. Treated
      muscles underwent massive atrophy while still displaying significant amounts of
      alpha1S in the tubular system and being not paralysed. This atrophy implicated
      the autophagy pathway, which was triggered by neuronal nitric oxide synthase
      redistribution, activation of FoxO3A, upregulation of autophagy-related genes and
      autophagosome formation. Subcellular investigations showed that this atrophy was
      correlated with the disappearance of a minor fraction of alpha1S located
      throughout the sarcolemma. Our results reveal for the first time that this
      sarcolemmal fraction could have a role in a signalling pathway determining muscle
      anabolic or catabolic state and might act as a molecular sensor of muscle
      activity.

PMID- 20033061
TI  - A fast dynamic mode of the EF-G-bound ribosome.
AB  - A key intermediate in translocation is an 'unlocked state' of the pre
      translocation ribosome in which the P-site tRNA adopts the P/E hybrid state, the
      L1 stalk domain closes and ribosomal subunits adopt a ratcheted configuration.
      Here, through two- and three-colour smFRET imaging from multiple structural
      perspectives, EF-G is shown to accelerate structural and kinetic pathways in the
      ribosome, leading to this transition. The EF-G-bound ribosome remains highly
      dynamic in nature, wherein, the unlocked state is transiently and reversibly
      formed. The P/E hybrid state is energetically favoured, but exchange with the
      classical P/P configuration persists; the L1 stalk adopts a fast dynamic mode
      characterized by rapid cycles of closure and opening. These data support a model
      in which P/E hybrid state formation, L1 stalk closure and subunit ratcheting are
      loosely coupled, independent processes that must converge to achieve the unlocked
      state. The highly dynamic nature of these motions, and their sensitivity to
      conformational and compositional changes in the ribosome, suggests that
      regulating the formation of this intermediate may present an effective avenue for
      translational control.

PMID- 20033062
TI  - Position of the general transcription factor TFIIF within the RNA polymerase II
      transcription preinitiation complex.
AB  - The RNA polymerase (pol) II general transcription factor TFIIF functions at
      several steps in transcription initiation including preinitiation complex (PIC)
      formation and start site selection. We find that two structured TFIIF domains
      bind Pol II at separate locations far from the active site with the TFIIF
      dimerization domain on the Pol II lobe and the winged helix domain of the TFIIF
      small subunit Tfg2 above the Pol II protrusion where it may interact with
      upstream promoter DNA. Binding of the winged helix to the protrusion is PIC
      specific. Anchoring of these two structured TFIIF domains at separate sites
      locates an essential and unstructured region of Tfg2 near the Pol II active site
      cleft where it may interact with flexible regions of Pol II and the general
      factor TFIIB to promote initiation and start site selection. Consistent with this
      mechanism, mutations far from the enzyme active site, which alter the binding of
      either structured TFIIF domains to Pol II, have similar defects in transcription
      start site usage.

PMID- 20033064
TI  - Neonatal gene transfer using lentiviral vector for murine Pompe disease: long
      term expression and glycogen reduction.
AB  - Pompe disease results from the deficiency of the lysosomal enzyme acid alpha
      glucosidase (GAA), leading to accumulated glycogen in the heart and the skeletal
      muscles, which causes cardiomyopathy and muscle weakness. In this study, we
      tested the feasibility of gene therapy for Pompe disease using a lentivirus
      vector (LV). Newborn GAA knockout mice were treated with intravenous injection of
      LV encoding human GAA (hGAA) through the facial superficial temporal vein. The
      transgene expression in the tissues was analyzed up to 24 weeks after treatment.
      Our results showed that the recombinant LV was efficient not only in increasing
      the GAA activity in tissues but also in decreasing their glycogen content. The
      examination of histological sections showed clearence of the glycogen storage in
      skeletal and cardiac muscles 16 and 24 weeks after a single vector injection.
      Levels of expressed hGAA could be detected in serum of treated animals until 24
      weeks. No significant immune reaction to transgene was detected in most treated
      animals. Therefore, we show that LV-mediated delivery system was effective in
      correcting the biochemical abnormalities and that this gene transfer system might
      be suitable for further studies on delivering GAA to Pompe disease mouse models.

PMID- 20033065
TI  - Inhibitory efficacy of hypoxia-inducible factor 1alpha short hairpin RNA plasmid
      DNA-loaded poly (D, L-lactide-co-glycolide) nanoparticles on choroidal
      neovascularization in a laser-induced rat model.
AB  - The aim of this study was to evaluate the possibility of poly (D, L-lactide-co
      glycolide) nanoparticle (NPs) as a gene vector for functional plasmid DNA (pDNA)
      and to investigate its inhibitory efficacy on experimental choroidal
      neovascularization (CNV). We developed intravitreal administered, hypoxia
      inducible factor 1alpha (HIF-1alpha) short hairpin RNA and green fluorescent
      protein (GFP) co-expressed pDNA-loaded NPs (pshHIF-1alpha NPs). CNV was induced
      by laser photocoagulation in 112 rats. The rats were then randomly assigned to be
      injected intravitreally with phosphate-buffered saline (PBS), blank NPs, naked
      pDNA, control pDNA NPs and pshHIF-1alpha NPs, respectively, and non-injection
      group was set as the control. Immunofluorescence staining, fluorescein fundus
      angiography and histologic analysis were performed to evaluate the inhibitory
      efficacy on CNV. The results showed that the expression of GFP preferentially
      localized in the retinal pigment epithelium cell layer and lasted for 4 weeks.
      The fluorescein leakage areas of CNV were significantly larger in the PBS, blank
      NPs, control pDNA NPs, non-injection group and naked pDNA group than in pshHIF
      1alpha NPs group (P<0.01). The mean thickness of the CNV lesions in the
      intravitreally pshHIF-1alpha NPs-treated group was significantly smaller than
      other groups (P<0.01). No signs of functional or ultrastructural destruction in
      retina were detected. Therefore, pshHIF-1alpha NPs may act as a novel therapeutic
      option to transfer specific pDNA and inhibit the formation of experimental CNV.

PMID- 20033066
TI  - Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment
      of recurrent ovarian cancer.
AB  - A phase-I trial to assess the safety and tolerability of human interleukin-12 (IL
      12) plasmid (phIL-12) formulated with a synthetic lipopolymer, polyethyleneglycol
      polyethyleneimine-cholesterol (PPC), was conducted on women with chemotherapy
      resistant recurrent ovarian cancer. A total of 13 patients were enrolled in four
      dose-escalating cohorts and treated with 0.6, 3, 12 or 24 mg m(-2) of the
      formulated plasmid once every week for 4 weeks. Administration of phIL-12/PPC was
      generally safe and well-tolerated. Common side effects included low-grade fever
      and abdominal pain. Stable disease and reduction in serum CA-125 levels were
      clinically observed in some patients. Measurable levels of IL-12 plasmid were
      detectable in PF samples collected throughout the course of phIL-12/PPC
      treatment. In comparison, serum samples either did not contain detectable amounts
      of plasmid DNA or contained <1% of the amount found in the corresponding PF
      samples. Treatment-related increases in IFN-gamma levels were observed in PF but
      not in serum. These data demonstrate that IL-12 gene delivery with a synthetic
      delivery system is feasible for ovarian cancer patients.

PMID- 20033063
TI  - The ILK/PINCH/parvin complex: the kinase is dead, long live the pseudokinase!
AB  - Dynamic interactions of cells with their environment regulate multiple aspects of
      tissue morphogenesis and function. Integrins are the major class of cell surface
      receptors that recognize and bind extracellular matrix proteins, resulting in the
      engagement and organization of the cytoskeleton as well as activation of
      signalling pathways to regulate cell behaviour and morphogenetic processes. The
      ternary complex of integrin-linked kinase (ILK), PINCH, and parvin (IPP complex),
      which was identified more than a decade ago, interacts with the cytoplasmic tail
      of beta integrins and couples them to the actin cytoskeleton. In addition, ILK
      has been shown to act as a serine/threonine kinase and to directly activate
      several signalling pathways downstream of integrins. However, the kinase activity
      of ILK and the precise functions of the IPP complex have remained elusive and
      controversial. This review focuses on the recent advances made towards
      understanding the specialized roles this complex and its individual components
      have acquired during evolution.

PMID- 20033067
TI  - Crenarchaeol dominates the membrane lipids of Candidatus Nitrososphaera
      gargensis, a thermophilic group I.1b Archaeon.
AB  - Analyses of archaeal membrane lipids are increasingly being included in
      ecological studies as a comparatively unbiased complement to gene-based
      microbiological approaches. For example, crenarchaeol, a glycerol dialkyl
      glycerol tetraether (GDGT) with a unique cyclohexane moiety, has been postulated
      as biomarker for ammonia-oxidizing Archaea (AOA). Crenarchaeol has been detected
      in Nitrosopumilus maritimus and 'Candidatus Nitrosocaldus yellowstonii'
      representing two of the three lineages within the Crenarchaeota containing
      described AOA. In this paper we present the membrane GDGT composition of
      'Candidatus Nitrososphaera gargensis', a moderately thermophilic AOA, and the
      only cultivated Group I.1b Crenarchaeon. At a cultivation temperature of 46
      degrees C, GDGTs of this organism consisted primarily of crenarchaeol, its
      regioisomer, and a novel GDGT. Intriguingly, 'Ca. N. gargensis' is the first
      cultivated archaeon to synthesize substantial amounts of the crenarchaeol
      regioisomer, a compound found in large relative abundances in tropical ocean
      water and some soils, and an important component of the TEX(86) paleothermometer.
      Intact polar lipid (IPL) analysis revealed that 'Ca. N. gargensis' synthesizes
      IPLs similar to those reported for the Goup I.1a AOA, Nitrosopumilus maritimus
      SCMI, in addition to IPLs containing uncharacterized headgroups. Overall, the
      unique GDGT composition of 'Ca. N. gargensis' extends the known taxonomic
      distribution of crenarchaeol synthesis to the Group I.1b Crenarchaeota,
      implicating this clade as a potentially important source of crenarchaeol in soils
      and moderately high temperature environments. Moreover, this work supports the
      hypothesis that crenarchaeol is specific to all AOA and highlights specific
      lipids, which may prove useful as biomarkers for 'Ca. N. gargensis'-like AOA.

PMID- 20033069
TI  - Microtoming coupled to microarray analysis to evaluate the spatial metabolic
      status of Geobacter sulfurreducens biofilms.
AB  - Further insight into the metabolic status of cells within anode biofilms is
      essential for understanding the functioning of microbial fuel cells and
      developing strategies to optimize their power output. Cells throughout anode
      biofilms of Geobacter sulfurreducens reduced the metabolic stains: 5-cyano-2,3
      ditolyl tetrazolium chloride and Redox Green, suggesting metabolic activity
      throughout the biofilm. To compare the metabolic status of cells growing close to
      the anode versus cells in the outer portion of the anode biofilm, anode biofilms
      were encased in resin and sectioned into inner (0-20 microm from anode surface)
      and outer (30-60 microm) fractions. Transcriptional analysis revealed that, at a
      twofold threshold, 146 genes had significant (P<0.05) differences in transcript
      abundance between the inner and outer biofilm sections. Only 1 gene, GSU0093, a
      hypothetical ATP-binding cassette transporter, had significantly higher
      transcript abundances in the outer biofilm. Genes with lower transcript abundance
      in the outer biofilm included genes for ribosomal proteins and NADH
      dehydrogenase, suggesting lower metabolic rates. However, differences in
      transcript abundance were relatively low (<threefold) and the expression of genes
      for the tricarboxylic acid cycle enzymes was not significantly lower. Lower
      expression of genes involved in stress responses in the outer biofilm may reflect
      the development of low pH near the surface of the anode. The results of this
      study suggest that cells throughout the biofilm are metabolically active and can
      potentially contribute to current production. The microtoming/microarray strategy
      described here may be useful for evaluating gene expression with depth in a
      diversity of microbial biofilms.

PMID- 20033068
TI  - Cultivation and quantitative proteomic analyses of acidophilic microbial
      communities.
AB  - Acid mine drainage (AMD), an extreme environment characterized by low pH and high
      metal concentrations, can support dense acidophilic microbial biofilm communities
      that rely on chemoautotrophic production based on iron oxidation. Field
      determined production rates indicate that, despite the extreme conditions, these
      communities are sufficiently well adapted to their habitats to achieve primary
      production rates comparable to those of microbial communities occurring in some
      non-extreme environments. To enable laboratory studies of growth, production and
      ecology of AMD microbial communities, a culturing system was designed to
      reproduce natural biofilms, including organisms recalcitrant to cultivation. A
      comprehensive metabolic labeling-based quantitative proteomic analysis was used
      to verify that natural and laboratory communities were comparable at the
      functional level. Results confirmed that the composition and core metabolic
      activities of laboratory-grown communities were similar to a natural community,
      including the presence of active, low abundance bacteria and archaea that have
      not yet been isolated. However, laboratory growth rates were slow compared with
      natural communities, and this correlated with increased abundance of stress
      response proteins for the dominant bacteria in laboratory communities.
      Modification of cultivation conditions reduced the abundance of stress response
      proteins and increased laboratory community growth rates. The research presented
      here represents the first description of the application of a metabolic labeling
      based quantitative proteomic analysis at the community level and resulted in a
      model microbial community system ideal for testing physiological and ecological
      hypotheses.

PMID- 20033070
TI  - Biogeography of soil archaea and bacteria along a steep precipitation gradient.
AB  - For centuries, biodiversity has spellbound biologists focusing mainly on
      macroorganism's diversity and almost neglecting the geographic mediated dynamics
      of microbial communities. We surveyed the diversity of soil bacteria and archaea
      along a steep precipitation gradient ranging from the Negev Desert in the south
      of Israel (<100 mm annual rain) to the Mediterranean forests in the north (>900
      mm annual rain). Soil samples were retrieved from triplicate plots at five long
      term ecological research stations, collected from two types of patches: plant
      interspaces and underneath the predominant perennial at each site. The molecular
      fingerprint of each soil sample was taken using terminal restriction length
      polymorphism of the 16S rRNA gene to evaluate the bacterial and archaeal
      community composition and diversity within and across sites. The difference in
      community compositions was not statistically significant within sites (P=0.33 and
      0.77 for bacteria and archaea, respectively), but it differed profoundly by
      ecosystem type. These differences could largely be explained by the precipitation
      gradient combined with the vegetation cover: the archaeal and bacterial
      operational taxonomic units were unique to each climatic region, that is, arid,
      semiarid and Mediterranean (P=0.0001, for both domains), as well as patch type
      (P=0.009 and 0.02 for bacteria and archaea, respectively). Our results suggest
      that unlike macroorganisms that are more diverse in the Mediterranean ecosystems
      compared with the desert sites, archaeal and bacterial diversities are not
      constrained by precipitation. However, the community composition is unique to the
      climate and vegetation cover that delineates each ecosystem.

PMID- 20033071
TI  - Effects of freeze-thaw cycles on anaerobic microbial processes in an Arctic
      intertidal mud flat.
AB  - Insight into the effects of repeated freezing and thawing on microbial processes
      in sediments and soils is important for understanding sediment carbon cycling at
      high latitudes acutely affected by global warming. Microbial responses to
      repeated freeze-thaw conditions were studied in three complementary experiments
      using arctic sediment collected from an intertidal flat that is exposed to
      seasonal freeze-thaw conditions (Ymerbukta, Svalbard, Arctic Ocean). The sediment
      was subjected to oscillating freeze-thaw incubations, either gradual, from -5 to
      4 degrees C, or abrupt, from -20 to 10 degrees C. Concentrations of low-molecular
      weight carboxylic acids (volatile fatty acids) were measured and sulfate
      reduction was assessed by measuring (35)S sulfate reduction rates (SRRs). Gradual
      freeze-thaw incubation decreased microbial activity in the frozen state to 0.25 %
      of initial levels at 4 degrees C, but activity resumed rapidly reaching >60 % of
      initial activity in the thawed state. Exposure of sediments to successive large
      temperature changes (-20 versus 10 degrees C) decreased SRR by 80% of the initial
      activity, suggesting that a fraction of the bacterial community recovered rapidly
      from extreme temperature fluctuations. This is supported by 16S rRNA gene-based
      denaturing gradient gel electrophoresis profiles that revealed persistence of the
      dominant microbial taxa under repeated freeze-thaw cycles. The fast recovery of
      the SRRs suggests that carbon mineralization in thawing arctic sediment can
      resume without delay or substantial growth of microbial populations.

PMID- 20033073
TI  - Angiotensin inhibition and malignancies: a question of hydration.

PMID- 20033074
TI  - Neuropeptide Y gene functional polymorphism influences susceptibility to
      hypertension in Indian population.
AB  - Hypertension is an independent determinant of cardiovascular risk, a phenotype
      that usually has a strong genetic component. Neuropeptide Y (NPY) plays an
      important role in BP homeostasis. The aim of this study was to investigate the
      possible influence of NPY polymorphisms on hypertension in a South Indian
      population. A total of 252 subjects (132 controls and 120 hypertensives) were
      analysed for T1128C, G1258A and A7735G polymorphisms in the NPY gene. Body mass
      index (BMI), pulse, SBP and DBP were assessed. Direct sequencing of PCR products
      was adopted for genotyping. All three polymorphisms were found to be in Hardy
      Weinberg equilibrium. Additive, dominant and recessive models were tested using
      multivariate regression analysis. The results of our study reveal a significant
      association between T1128C and hypertension even after adjusting for age, sex and
      BMI. The adjusted OR (95% confidence interval) for the recessive model was 0.56
      (0.33-0.95). The other two polymorphic sites (G1258A and A7735G) are not
      associated with hypertension. The Pro7 allele of the T1128C polymorphic site
      containing haplotype (CGA) is associated with hypertension (P=0.049), but the
      combined haplotypes did not show any evidence of haplotype-phenotype association
      (global P=0.129). These data support the hypothesis that hypertension is
      influenced by the NPY T1128C polymorphism.

PMID- 20033076
TI  - Lagging laws.

PMID- 20033075
TI  - Aliskiren for geriatric lowering of systolic hypertension: a randomized
      controlled trial.
AB  - Efficacy and safety of the direct renin inhibitor aliskiren was compared with
      ramipril for treatment of essential systolic hypertension in elderly patients. A
      36-week, randomized, double-blind, parallel-group, active-controlled, optional
      titration study was performed in 901 patients (aliskiren, n=457; ramipril, n=444)
      > or =65 years of age with systolic blood pressure (SBP) > or =140 mm Hg.
      Aliskiren 150-300 mg per day or ramipril 5-10 mg per day for was administered for
      12 weeks with optional add-on therapy of hydrochlorothiazide (12.5-25 mg per day)
      at week 12 and amlodipine (5-10 mg per day) at week 22. The primary end point was
      non-inferiority of aliskiren vs ramipril monotherapy for change from baseline in
      mean sitting SBP (msSBP) at week 12. Decreases from baseline msSBP and mean
      sitting diastolic BP with aliskiren monotherapy (-14.0 and -5.1 mm Hg,
      respectively) were non-inferior (P<0.001 for both values) and superior to
      ramipril monotherapy (-11.6, -3.6 mm Hg; P=0.02, P<0.01, respectively). More
      patients achieved BP control with aliskiren (42%) than ramipril (33%; P<0.01). At
      week 36, fewer patients receiving aliskiren-based therapy required add-on
      treatment with hydrochlorothiazide or amlodipine (P=0.01 and 0.048,
      respectively). Tolerability was similar, but more patients receiving ramipril
      reported cough (P<0.001). In elderly patients with systolic hypertension,
      aliskiren proved to be more effective and better overall anti-hypertensive
      therapy compared to ramipril.

PMID- 20033077
TI  - Testing the glutamate hypothesis of schizophrenia.

PMID- 20033078
TI  - Ion pumps get more glamorous.

PMID- 20033079
TI  - Sonic Hedgehog gets another role.

PMID- 20033080
TI  - Polar exploration.

PMID- 20033081
TI  - Postdockin' in the free world.

PMID- 20033072
TI  - Comparative community genomics in the Dead Sea: an increasingly extreme
      environment.
AB  - Owing to the extreme salinity ( approximately 10 times saltier than the oceans),
      near toxic magnesium levels (approximately 2.0 M Mg(2+)), the dominance of
      divalent cations, acidic pH (6.0) and high-absorbed radiation flux rates, the
      Dead Sea represents a unique and harsh ecosystem. Measures of microbial presence
      (microscopy, pigments and lipids) indicate that during rare bloom events after
      exceptionally rainy seasons, the microbial communities can reach high densities.
      However, most of the time, when the Dead Sea level is declining and halite is
      precipitating from the water column, it is difficult to reliably measure the
      presence of microorganisms and their activities. Although a number of halophilic
      Archaea have been previously isolated from the Dead Sea, polar lipid analyses of
      biomass collected during Dead Sea blooms suggested that these isolates were not
      the major components of the microbial community of these blooms. In this study,
      in an effort to characterize the perennial microbial community of the Dead Sea
      and compare it with bloom assemblages, we performed metagenomic analyses of
      concentrated biomass from hundreds of liters of brine and of microbial material
      from the last massive Dead Sea bloom. The difference between the two conditions
      was reflected in community composition and diversity, in which the bloom was
      different and less diverse from the residual brine population. The distributional
      patterns of microbial genes suggested Dead Sea community trends in mono- and
      divalent cation metabolisms as well as in transposable elements. This may
      indicate possible mechanisms and pathways enabling these microbes to survive in
      such a harsh environment.

PMID- 20033082
TI  - The 20 W sleep-walkers.

PMID- 20033083
TI  - Autophagy: where next?

PMID- 20033084
TI  - Opening a new DOR to autophagy.

PMID- 20033085
TI  - Legislation, social licence and primate research.

PMID- 20033086
TI  - Helicobacter pylori induces NF-kappaB independent of CagA.

PMID- 20033089
TI  - The Bronze Age of science in Spain.

PMID- 20033090
TI  - The science of online dating. Can the application of science to unravel the
      biological basis of love complement the traditional, romantic ideal of finding a
      soul mate?

PMID- 20033091
TI  - The missing link. Viruses revise evolutionary theory.

PMID- 20033092
TI  - Solitons of singly resonant optical parametric oscillators: errata.

PMID- 20033093
TI  - Optimizing allocation for a delayed influenza vaccination campaign.
AB  - During unexpected infectious disease outbreaks, public health agencies must make
      effective use of limited resources. Vaccine distribution may be delayed and
      staggered through time, as underscored by the 2009 H1N1 influenza pandemic. Using
      a mathematical model parametrized with data from the 2009 H1N1 pandemic, we found
      that optimal allocations of vaccine among people in different age groups and
      people with high-risk conditions depends on the schedule of vaccine availability
      relative to the progress of the epidemic. For the projected schedule of H1N1
      vaccine availability, the optimal strategy to reduce influenza-related deaths is
      to initial target high-risk people, followed by school-aged children (5--17) and
      then young adults (18--44). The optimal strategy to minimize hospitalizations,
      however, is to target ages 5--44 throughout the vaccination campaign, with only a
      tiny amount of vaccine used on high-risk people. We find that optimizing at each
      vaccine release time independently does not give the overall optimal strategy. In
      this manuscript, we derive policy recommendations for 2009 H1N1 vaccine
      allocation using a mathematical model. In addition, our optimization procedures,
      which consider staggered releases over the entire epidemic altogether, are
      applicable to other outbreaks where not all supplies are available initially.

PMID- 20033107
TI  - Work phobia and sickness leave certificates.

PMID- 20033108
TI  - Screening for HIV-related PTSD: sensitivity and specificity of the 17-item
      Posttraumatic Stress Diagnostic Scale (PDS) in identifying HIV-related PTSD among
      a South African sample.
AB  - OBJECTIVES: The identification of HIV-positive patients who exhibit criteria for
      Posttraumatic Stress Disorder (PTSD) and related trauma symptomatology is of
      clinical importance in the maintenance of their overall wellbeing. This study
      assessed the sensitivity and specificity of the 17-item Posttraumatic Stress
      Diagnostic Scale (PDS), a self-report instrument, in the detection of HIV-related
      PTSD. An adapted version of the PTSD module of the Composite International
      Diagnostic Interview (CIDI) served as the gold standard. METHOD: 85 HIV-positive
      patients diagnosed with HIV within the year preceding data collection were
      recruited by means of convenience sampling from three HIV clinics within primary
      health care facilities in the Boland region of South Africa. RESULTS: A
      significant association was found between the 17-item PDS and the adapted PTSD
      module of the CIDI. A ROC curve analysis indicated that the 17-item PDS correctly
      discriminated between PTSD caseness and non-caseness 74.9% of the time. Moreover,
      a PDS cut-off point of > or = 15 yielded adequate sensitivity (68%) and 1
      specificity (65%). The 17-item PDS demonstrated a PPV of 76.0% and a NPV of
      56.7%. CONCLUSION: The 17-item PDS can be used as a brief screening measure for
      the detection of HIV-related PTSD among HIV-positive patients in South Africa.

PMID- 20033109
TI  - Sleep and daytime sleepiness in methylphenidate medicated and un-medicated
      children with attention-deficit/hyperactivity disorder (ADHD).
AB  - OBJECTIVE: Excessive daytime sleepiness due to any cause can result in various
      symptoms similar to those used for the diagnosis of attention
      deficit/hyperactivity disorder (ADHD). A common treatment for children diagnosed
      with ADHD is methylphenidate which is also used to treat excessive daytime
      sleepiness. This paper reports on a study which compared the perceived levels of
      daytime sleepiness and prevalence of sleep disorders in medicated and un
      medicated children with ADHD. METHOD: The sample consisted of two matched groups
      of children who had been formally diagnosed with ADHD. One group (n=12) was
      taking immediate release methylphenidate twice daily, while the other group
      (n=11) had never, and were not currently, taking any medication. The two groups,
      as well as their parents, rated their levels of daytime sleepiness at three
      points in a single day. RESULTS: Significantly higher levels of daytime
      sleepiness were reported by the parents of the un-medicated children between the
      hours of 13:00 and 15:00, compared to the medicated children. The medicated
      children became increasingly sleepier from the first to the second measurement in
      both the morning and afternoon. There was no significant difference in the number
      of sleep disorders/disruptions reported by the parents of either group.
      CONCLUSION: In a group of children with ADHD taking methylphenidate, there was a
      significant increase in sleepiness a few hours after taking the medication, which
      may then have a significant impact on their learning. The data also imply that
      part of the mechanism of action of methylphenidate effects in these children may
      be by reduction of daytime sleepiness.

PMID- 20033110
TI  - The psychological impact of vitiligo in adult Sudanese patients.
AB  - OBJECTIVE: Vitiligo is a chronic skin disease that causes loss of pigment,
      resulting in irregular pale patches of skin. The disease has profound
      psychological consequences. These effects range from mild embarrassment to a
      severe loss of self-confidence and social anxiety, especially for those who have
      lesions on exposed skin. The study sought to determine the psychological impact
      of vitiligo in Sudanese patients. METHOD: This study is a cross-sectional,
      clinical-epidemiological and hospital-based study, undertaken in Khartoum
      Dermatologic Hospital (KDH). The data was collected between June 2007 and
      November 2007. 111 adult patients were enrolled sequentially during the study
      period and they were tested using the 12-item General Health Questionnaire (GHQ
      12). RESULTS: Psychological disturbances as a consequence of vitiligo were found
      in 36 (31 %) adult patients. Patients with mild psychological disturbances were
      found in 20 of these patients and severe disturbances in 16. CONCLUSION:
      Psychological consequences are common in patients with vitiligo.

PMID- 20033111
TI  - Screening for and monitoring of cardio-metabolic risk factors in outpatients with
      severe mental illness in a primary care setting.
AB  - OBJECTIVE: Recent findings suggest that premature death in patients with severe
      mental illness (SMI) can be attributed to the high comorbidity of cardio
      metabolic disorders. This study investigated the prevalence and monitoring of
      some risk factors for cardio-metabolic disease in a cohort with SMI, compared to
      the general medical population. METHOD: 101 participants with SMI and 100
      controls were recruited from a primary care clinic. Assessments of risk factors
      with standard clinical measurements were done after healthcare workers and
      patient-participants had completed the structured questionnaires. Clinical files
      were reviewed to determine frequency of monitoring of risk factors. RESULTS: We
      found no differences between the groups in demographic variables. A similar
      prevalence of abnormal blood pressure (BP), increased Body Mass Index (BMI) and
      increased waist circumference was noted in both groups. Females in both groups
      were more likely to have an abnormal waist circumference. Patients with SMI were
      significantly less likely to have recordings of their weight or BP in their
      clinic file. Healthcare workers and patients with SMI were largely unaware of the
      increased risk of cardio-metabolic illness. CONCLUSION: This study suggests that
      patients with SMI received poorer health monitoring than other patients attending
      a primary care clinic and that both healthcare workers and patients were poorly
      informed about the increased risk of cardio-metabolic disorders in patients with
      SMI.

PMID- 20033113
TI  - Psychological morbidity and job satisfaction amongst medical interns at a
      Nigerian teaching hospital.

PMID- 20033112
TI  - Perceived economic and behavioural effects of the mentally ill on their relatives
      in Kenya: a case study of the Mathari Hospital.
AB  - OBJECTIVE: There is no documented evidence in Kenya on relatives' perceptions of
      economic and behavioural effects of the mentally ill patients and their coping
      mechanisms. To document what relatives of mentally ill patients perceive to be
      the economic effects of the patients on the family and how they are affected by
      and cope with the disturbed behaviours of the patients. METHOD: This was a cross
      sectional descriptive study conducted at the Mathari Psychiatric Hospital.
      Informed consent was obtained from both the relatives and the patients admitted
      at the hospital. Data on socio-demographic and economic profiles were obtained
      from the patients and their relatives. The relatives were interviewed using a
      structured questionnaire to determine what they perceived to be the economic
      effects of the mental illness, how the various disturbed behaviours of the
      mentally ill affected them, and how they coped. The data were analysed using SPSS
      version 11.5 and results are presented in narratives and tables. RESULTS: One
      hundred and seventy-five relatives and 107 patients were recruited and
      interviewed. The patients were younger and better educated but economically less
      well off than their relatives. The relatives perceived that the mentally ill
      patients caused financial constraints and that various disturbed behaviours,
      particularly, verbal and physical aggression and refusal of the patient to take
      medicine or go to hospital, affected the family in different ways. Different
      coping mechanisms were used, depending on whether or not the behaviours were
      intrusive. CONCLUSION: Mentally ill patients adversely affect their families in
      diverse ways. There is need for appropriate policy to address the needs of
      families with mentally ill patients at the family and community levels. However,
      these must be evidence-based and this calls for further research.

PMID- 20033114
TI  - [Course system of the Working Group for Gastro-intestinal Surgery Davos].
AB  - Training in technical skills is essential for advanced surgical education.
      Training is moving more and more from the operating room to surgical training
      laboratories. A crucial impulse for this development came from Davos, where the
      first skills course was organized in 1984 after the formation of the Working
      Group for Gastro-intestinal (GI) Surgery (AGC Davos). Since this first course
      more than 5,000 residents have successfully completed the GI skills training
      course in Davos and many of the alumni are themselves teaching surgery today. The
      level and quality of this course has remained stable for 27 years on a high
      quality level although teaching has continuously been adjusted to modern
      techniques. The language of this international workshop is English. The number of
      applications exceeds the course capacity every year, which is an indication for
      the need of such training courses and should be principally included into the
      skills curriculum for surgeons.

PMID- 20033115
TI  - [Human papillomaviruses in the pathogenesis of intraepithelial neoplasia (AIN)
      and carcinoma of the anus].
AB  - HPV infections have been implicated in the pathogenesis of anal cancers. The mode
      of infection and subsequent transformation resembles very much the pathogenesis
      of cervical and other HPV-associated cancers. The molecular dissection of
      individual steps required to achieve cellular transformation within an HPV
      infected cell led to the identification of novel biomarkers that make it possible
      to identify HPV-transformed cells with substantially higher precision in
      comparison to conventional methods. Since effective antiretroviral therapy allows
      for possible long-term survival of HIV-infected individuals who are at very high
      risk to develop HPV-associated cancers in the anogenital tract, these new
      developments have become increasingly relevant for practicing dermatologists and
      proctologists. We here briefly review the basic concepts and some clinical
      applications of this recent research.

PMID- 20033117
TI  - [Diseases of the orbit: an interdisciplinary specialized field].

PMID- 20033116
TI  - [Clinical anatomy of the temporal bone: taxonomy, topography and important
      variations].
AB  - Detailed knowledge of the complicated anatomy and topography of the temporal bone
      is a crucial basis for successful ear surgery. In particular, the topographical
      relations to the essential neighbouring structures (e.g. intratemporal vessels
      and nerves, neighbouring spaces, especially the endocranium) are of vital
      importance. Furthermore, typical landmarks play an essential role in topographic
      orientation. However, this knowledge cannot be acquired from lectures or books,
      but can only be achieved by independently performing numerous dissections and
      drill exercises on the temporal bone, once a theoretical understanding of the
      various structures and regions has been gained on the basis of a clearly defined
      nomenclature. Furthermore, there are essential anatomical variations which may
      lead to complicated anatomical conditions. The surgeon must also be familiar with
      these peculiarities.

PMID- 20033118
TI  - [Inflammatory diseases of the paranasal sinuses: orbital and periorbital
      complications].
AB  - BACKGROUND: In most cases bacterial infections of orbital and periorbital
      structures constitute inflammatory processes transmitted from the paranasal sinus
      system. The anatomical continuity of the paranasal sinuses to the orbit and also
      to the brain is the main reason for the occurrence of serious or even life
      threatening complications. MATERIAL AND METHODS: Under consideration of the
      literature and selected clinical cases, the pathogenesis, diagnostic standards
      and therapy strategies are discussed with respect to the stage of the disease and
      the clinical course. CONCLUSIONS: Inflammatory periorbital and orbital
      complications require immediate otorhinolaryngological diagnosis and therapy and
      therefore, interdisciplinary cooperation with ophthalmologists and radiologists
      is indispensable. In particular the infrequent, but still seriously life
      threatening processes associated with a 5-10% fatality rate must be diagnosed and
      treated as early as possible. In these cases the inclusion of neurosurgery and
      intensive care into a complex treatment management is necessary in order to
      prevent severe progression with endocrinal complications or even fatal outcome.

PMID- 20033119
TI  - [Aneurysmal bone cyst of the ethmoid sinus and skull base in a 3-year old child:
      a rare location of a benign bone lesion].
AB  - Aneurysmal bone cyst is a benign osteolytic lesion in childhood and adolescence
      which primarily arises in metaphyseal long bones. Its presence in bones of the
      skull base is very rare. In a 3-year old girl presenting with proptosis, MRI
      demonstrated a well-defined displacing growing mass in the ethmoid sinus, orbita
      and anterior fossa. The histopathologic examination of biopsy specimens confirmed
      an aneurysmal bone cyst. Despite radical surgery the child suffered from two
      recurrences of the lesion in the first year after initial diagnosis. There has
      been no subsequent recurrence during the last 3 years. Since this lesion is
      rarely seen at the skull base, is difficult to differentiate clinically and by
      histopathology and may take an abnormal course, it is described in this case
      report to emphasize that it should be included in the differential diagnosis of
      ENT tumors at this location.

PMID- 20033120
TI  - [Metabolit-induced bioluminescence for tumor prediction: detection of metabolites
      in tumors of the head and neck region].
AB  - Solid tumors show an altered metabolism with respect to glycolysis in comparison
      to normal tissue. Recently, the determination of different glycolytic metabolites
      for tumor diagnosis and therapeutic decision-making became the focus of interest
      for various research groups. In particular an increased lactate concentration in
      tumor tissue appears to be a predictor of an adverse prognosis. Imaging of
      induced bioluminescence in rapidly frozen tumor biopsies is an established
      technique for the detection of selected substances. In this method the
      metabolites of interest are biochemically linked to luciferases. A microscopic
      photon counting system registers the light intensity and after calibration
      reflects the concentration distribution of metabolites. In contrast to other
      methods it is possible to detect different metabolites from one specific area of
      tissue. Preliminary results of a pilot study on oral cancer patients suggest a
      prognostic impact in terms of high lactate concentrations being associated with
      poor survival. This technique could increase the validity and significance of
      tumor grading and might be supportive decision guidance for tumor therapy in the
      future.

PMID- 20033121
TI  - [Endocrine ophthalmopathy: surgical treatment].
AB  - Since the transpalpebral decompression of the orbit by removal of intraorbital
      fat was introduced in 1985, this technique has become the state of the art in
      surgical therapy for Graves' ophthalmopathy at the authors' institution. Our
      experience with a series of 3,210 orbital decompressions in 1,635 patients with
      endocrine ophthalmopathy represents the largest collective of such patients that
      has been published yet to our knowledge. Over time the technique has proved to be
      reliable, effective, safe, and easily performed by a trained and experienced
      oculoplastic surgeon with long-lasting results, leading to improvement not only
      in visual function but also in well-being and in patients' social life, with a
      high benefit to low risk ratio. The promising and satisfying results demonstrated
      earliest in 1988 have been confirmed in further evaluation at our clinic and
      others. In summary, this technique, which is associated with very low morbidity,
      is our method of choice in moderate to severe cases of exophthalmos and even in
      functionally asymptomatic patients with mild to moderate aesthetic impairment.
      However, it has to be emphasized that this complex and multifactorial disorder
      often requires a broad range of long-term medical attendance. Postoperatively the
      majority of patients showed significant improvements of ocular protrusion,
      diplopia, visual acuity, swelling of eyelids, headache and retrobulbar "burn". In
      very rare instances, the surgical technique can be performed as a one-stage
      procedure. In severe cases (proptosis >28 or extreme muscle hypertrophy),
      lipectomy can be combined with expansion of the bony orbital cavity (<1%
      patients).

PMID- 20033122
TI  - Microbial degradation of usnic acid in the reindeer rumen.
AB  - Reindeer (Rangifer tarandus) eat and utilize lichens as an important source of
      energy and nutrients in winter. Lichens synthesize and accumulate a wide variety
      of phenolic secondary compounds, such as usnic acid, as a defense against
      herbivores and to protect against damage by UV-light in solar radiation. We have
      examined where and to what extent these phenolic compounds are degraded in the
      digestive tract of the reindeer, with particular focus on usnic acid. Three male
      reindeer were given ad libitum access to a control diet containing no usnic acid
      for three weeks and then fed lichens ad libitum (primarily Cladonia stellaris)
      containing 9.1 mg/g DM usnic acid for 4 weeks. Usnic acid intake in reindeer on
      the lichen diet was 91-117 mg/kg BM/day. In spite of this, no trace of usnic acid
      or conjugates of usnic acid was found either in fresh rumen fluid, urine, or
      feces. This suggests that usnic acid is rapidly degraded by rumen microbes, and
      that it consequently is not absorbed by the animal. This apparent ability to
      detoxify lichen phenolic compounds may gain increased importance with future
      enhanced UV-B radiation expected to cause increased protective usnic acid/phenol
      production in lichens.

PMID- 20033123
TI  - A multi-scale study of Orthoptera species richness and human population size
      controlling for sampling effort.
AB  - Recent large-scale studies have shown that biodiversity-rich regions also tend to
      be densely populated areas. The most obvious explanation is that biodiversity and
      human beings tend to match the distribution of energy availability, environmental
      stability and/or habitat heterogeneity. However, the species-people correlation
      can also be an artefact, as more populated regions could show more species
      because of a more thorough sampling. Few studies have tested this sampling bias
      hypothesis. Using a newly collated dataset, we studied whether Orthoptera species
      richness is related to human population size in Italy's regions (average area
      15,000 km(2)) and provinces (2,900 km(2)). As expected, the observed number of
      species increases significantly with increasing human population size for both
      grain sizes, although the proportion of variance explained is minimal at the
      provincial level. However, variations in observed Orthoptera species richness are
      primarily associated with the available number of records, which is in turn well
      correlated with human population size (at least at the regional level). Estimated
      Orthoptera species richness (Chao2 and Jackknife) also increases with human
      population size both for regions and provinces. Both for regions and provinces,
      this increase is not significant when controlling for variation in area and
      number of records. Our study confirms the hypothesis that broad-scale human
      population-biodiversity correlations can in some cases be artefactual. More
      systematic sampling of less studied taxa such as invertebrates is necessary to
      ascertain whether biogeographical patterns persist when sampling effort is kept
      constant or included in models.

PMID- 20033125
TI  - [Incorrigibly structured--or can computers improve the results?].

PMID- 20033124
TI  - A multidisciplinary study of archaeological grape seeds.
AB  - We report here the first integrated investigation of both ancient DNA and
      proteins in archaeobotanical samples: medieval grape (Vitis vinifera L.) seeds,
      preserved by anoxic waterlogging, from an early medieval (seventh-eighth century
      A.D.) Byzantine rural settlement in the Salento area (Lecce, Italy) and a late
      (fourteenth-fifteenth century A.D.) medieval site in York (England). Pyrolysis
      gas chromatography mass spectrometry documented good carbohydrate preservation,
      whilst amino acid analysis revealed approximately 90% loss of the original
      protein content. In the York sample, mass spectrometry-based sequencing
      identified several degraded ancient peptides. Nuclear microsatellite locus (VVS2,
      VVMD5, VVMD7, ZAG62 and ZAG79) analysis permitted a tentative comparison of the
      genetic profiles of both the ancient samples with the modern varieties. The
      ability to recover microsatellite DNA has potential to improve biomolecular
      analysis on ancient grape seeds from archaeological contexts. Although the
      investigation of five microsatellite loci cannot assign the ancient samples to
      any geographic region or modern cultivar, the results allow speculation that the
      material from York was not grown locally, whilst the remains from Supersano could
      represent a trace of contacts with the eastern Mediterranean.

PMID- 20033126
TI  - [Clinically unclear painful swelling of the upper arm].
AB  - In contrast to the intramedullary (80%) and intracortical (14%) subtypes, the
      subperiostal subtype of aneurysmatic bone cysts (sABC) is relatively rare (6%).
      Females are affected more frequently than males, whereby the diaphysis is
      predominantly affected and less frequently the metaphysis of long bones as well
      as the vertebral column. Especially in conventional radiography sABCs can mimic
      aggressive lesions. Cross-sectional imaging can potentially reduce the wide range
      of differential diagnoses. Due to typical imaging features magnetic resonance
      imaging (MRI) is the most valuable modality to reduce the range of possible
      differential diagnoses. MRI usually presents a multicystic appearance with a
      hypointense rim of the lesion, contrast-enhancing cyst walls, fluid levels and
      edema-like changes in the adjacent tissue. In sABCs with solid components the
      diagnosis cannot be made with confidence and the suspicion must be confirmed by
      biopsy. The therapy of primary lesions consists of curettage or the complete
      excision of the sABC and the defects are subsequently filled with spongiosa or
      bone cement depending on the size of the lesion.

PMID- 20033127
TI  - [Clinical application of functional MRI for chronic epilepsy].
AB  - Functional magnetic resonance imaging (fMRI) is frequently used in the
      presurgical diagnostic procedure of epilepsy patients, in particular for
      lateralization of speech and memory and for localization of the primary motor
      cortex to delineate the epileptogenic lesion from eloquent brain areas. fMRI is
      one of the non-invasive procedures in the presurgical diagnostic process,
      together with medical history, seizure semiology, neurological examination,
      interictal and ictal EEG, structural MRI, video EEG monitoring and
      neuropsychology. This diagnostic sequence leads either to the decision for or
      against elective epilepsy surgery or to the decision to proceed with invasive
      diagnostic techniques (Wada test, intra-operative or extra-operative cortical
      stimulation). It is difficult to evaluate the contribution of the fMRI test in
      isolation to the validity of the entire diagnostic sequence. Complications such
      as memory loss and aphasia in temporal lobe resections or paresis after frontal
      lobe resections are rare and rarely of disastrous extent. This further
      complicates the evaluation of the clinical relevance of fMRI as a predictive
      tool. In this article studies which investigated the concordance between fMRI and
      other diagnostic gold standards will be presented as well as the association
      between presurgical fMRI and postsurgical morbidity.

PMID- 20033128
TI  - [Benign prostatic hyperplasia (BPH) : Surgical therapy options].
AB  - The surgical treatment options available today for benign prostatic hyperplasia
      (BPH) can take various forms and often follow a course of pharmacological
      therapy. In addition to conventional transurethral resection of the prostate
      (TURP) and its modifications (bipolar resection), which has represented the
      standard therapeutic option for decades, the focus of research and clinical
      application has shifted to alternative so-called "minimally invasive"
      instrumental techniques, such as transurethral microwave therapy (TUMT) and,
      particularly more recently, to the different laser-assisted techniques. By
      reviewing the current literature, preferably from randomized controlled trials,
      critical appraisals of the individual procedures are made.

PMID- 20033131
TI  - Antioxidant enzymatically modified isoquercitrin or melatonin supplementation
      reduces oxidative stress-mediated hepatocellular tumor promotion of oxfendazole
      in rats.
AB  - To clarify whether enzymatically modified isoquercitrin (EMIQ) or melatonin (MLT)
      supplementation reduces oxidative stress-mediated hepatocellular tumor-promoting
      effect of oxfendazole (OX), a benzimidazole anthelmintic, male rats were
      administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) and
      were fed a diet containing OX (500 ppm) for 10 weeks with or without EMIQ (2,000
      ppm) or MLT (100 ppm) in the drinking water after DEN initiation. One week after
      the commencement of the administration of OX, rats were subjected to two-thirds
      of partial hepatectomy. The number of GST-P-positive foci promoted by OX was
      significantly inhibited by the combined antioxidant EMIQ or MLT administration,
      and the area of GST-P-positive foci was inhibited by the administration of MLT.
      Real-time RT-PCR analysis revealed decreases in mRNA expression levels of
      cytochrome P450, family 2, subfamily b, polypeptide 2 (Cyp2b2) and malic enzyme 1
      (Me1) in the DEN-OX-EMIQ and DEN-OX-MLT groups and decreases in mRNA expression
      levels of Cyp1a1 and aldo-keto reductase family 7, member A3 (Akr7a3) in the DEN
      OX-MLT group compared to those in the DEN-OX group. In in vitro ROS production
      assay, inhibited production of NADPH-dependent ROS was observed by the treatment
      with EMIQ or MLT. These results suggest that coadministration of EMIQ or MLT
      suppresses the hepatocellular tumor-promoting activity of OX in rats through the
      decrease in ROS production by the activation of CYPs.

PMID- 20033129
TI  - The association between relationship markers of sexual orientation and suicide:
      Denmark, 1990-2001.
AB  - OBJECTIVE: Minority sexual orientation has been repeatedly linked to elevated
      rates of suicide attempts. Whether this translates into greater risk for suicide
      mortality is unclear. We investigated sexual orientation-related differences in
      suicide mortality in Denmark during the initial 12-year period following
      legalization of same-sex registered domestic partnerships (RDPs). METHOD: Using
      data from death certificates issued between 1990 and 2001 and population
      estimates from the Danish census, we estimated suicide mortality risk among
      individuals classified into one of three marital/cohabitation statuses:
      current/formerly in same-sex RDPs; current/formerly heterosexually married; or
      never married/registered. RESULTS: Risk for suicide mortality was associated with
      this proxy indicator of sexual orientation, but only significantly among men. The
      estimated age-adjusted suicide mortality risk for RDP men was nearly eight times
      greater than for men with positive histories of heterosexual marriage and nearly
      twice as high for men who had never married. CONCLUSIONS: Suicide risk appears
      greatly elevated for men in same-sex partnerships in Denmark. To what extent this
      is true for similar gay and bisexual men who are not in such relationships is
      unknown, but these findings call for targeted suicide prevention programs aimed
      at reducing suicide risk among gay and bisexual men.

PMID- 20033130
TI  - Occupation and mental health in a national UK survey.
AB  - OBJECTIVES: To measure the prevalence of common mental disorder (CMD) by
      occupation in a representative sample of Great Britain and to identify
      occupations with increased and decreased risk of CMD. METHODS: A cross-sectional
      interview-based survey was carried out including 5,497 working male and female
      respondents, 16-64 years from a stratified random survey of private households in
      Britain. Occupations were classified by the Standard Occupational Classification
      (SOC) into four groups: major, sub-major, minor and constituent unit groups.
      Common Mental Disorder was measured by the Revised Clinical Interview Schedule.
      RESULTS: Major SOC groups with higher prevalence of common mental disorder
      included clerical and secretarial, sales, and personal and protective services
      whereas craft and related, 'other' professional occupations and plant and machine
      operatives had lower prevalence compared to 13% overall prevalence in all adults.
      In sub-major SOC groups managers and administrators, teaching professionals,
      clerical and secretarial, 'other' sales and personal service occupations had
      higher prevalence whereas many professional and skilled occupations had lower
      prevalence. Specific SOC unit groups with higher prevalence included primary and
      secondary teachers, welfare community, youth workers, security staff, waiters,
      bar staff, nurse auxiliaries and care assistants. General managers in government
      and large organizations (OR=2.79, 95% CI 1.41-5.54), managers in transport and
      storing (OR=2.44, 95% CI 1.18-5.03), buyers and mobile sales persons (OR=2.48,
      95% CI 1.09-5.60), sales occupations (NES) (OR=2.78, 95% CI 1.25-6.19) and clerks
      (NES) (OR=2.71, 95% CI 1.59-4.61) had increased risk of common mental disorder
      relative to specialist managers adjusting for social and financial factors and
      physical ill-health. CONCLUSIONS: Occupations with higher risk of common mental
      disorder may be typified by high levels of job demands, especially emotional
      demands and lack of job security. The reasons why occupations have low rates of
      common mental disorder are varied and may include high levels of job discretion,
      good job training and clearly defined job tasks.

PMID- 20033132
TI  - Gamma-vinyl GABA increases nonvesicular release of GABA and glutamate in the
      nucleus accumbens in rats via action on anion channels and GABA transporters.
AB  - RATIONALE: gamma-Amino butyric acid (GABA) is a well-characterized inhibitory
      neurotransmitter in the central nervous system, which may also stimulate
      nonvesicular release of other neurotransmitters under certain conditions. We have
      recently reported that gamma-vinyl GABA (GVG), an irreversible GABA transaminase
      inhibitor, elevates extracellular GABA but fails to alter dopamine release in the
      nucleus accumbens (NAc). OBJECTIVES: Here, we investigated the mechanism(s) by
      which GVG elevates extracellular GABA levels and whether GVG also alters
      glutamate release in the NAc. MATERIALS AND METHODS: In vivo microdialysis was
      used to simultaneously measure extracellular NAc GABA and glutamate before and
      after GVG administration in freely moving rats. RESULTS: Systemic administration
      of GVG or intra-NAc local perfusion of GVG significantly increased extracellular
      NAc GABA and glutamate. GVG-enhanced GABA was completely blocked by intra-NAc
      local perfusion of 5-nitro-2, 3-(phenylpropylamino)-benzoic acid (NPPB), a
      selective anion channel blocker and partially blocked by SKF89976A, a type 1 GABA
      transporter inhibitor. GVG-enhanced glutamate was completely blocked by NPPB or
      SKF89976A. Tetrodotoxin, a voltage-dependent Na(+)-channel blocker, failed to
      alter GVG-enhanced GABA and glutamate. CONCLUSIONS: These data suggest that GVG
      enhanced extracellular GABA and glutamate are mediated predominantly by the
      opening of anion channels and partially by the reversal of GABA transporters.
      Enhanced extracellular glutamate may functionally attenuate the pharmacological
      action of GABA and prevent enhanced GABA-induced excess inhibition.

PMID- 20033133
TI  - Is the ten-item Questionnaire of Smoking Urges (QSU-brief) more sensitive to
      abstinence than shorter craving measures?
AB  - OBJECTIVE: The Questionnaire on Smoking Urges is now very widely used as a
      measure of craving but is considerably longer than alternatives in current use.
      Longer scales carry a significant cost in studies and clinical practice. This
      study compared the ten-item Questionnaire on Smoking Urges (QSU-brief) with six
      shorter measures of craving in terms of sensitivity to abstinence and
      reliability. METHODS: Sixty smokers were randomly assigned to continue smoking (N
      = 30) or abstain completely for 24 h (n = 30), by which time the craving would be
      expected to have increased. Craving was measured at baseline and after 24 h. The
      craving measures tested were the QSU-brief, the Minnesota Nicotine Withdrawal
      Scale (MNWS), the Mood and Physical Symptoms Scale (MPSS), the Shiffman Scale
      (SS), the Wisconsin Smoking Withdrawal Scale and the Cigarette Withdrawal Scale
      and a simple rating of 'craving' (CR). RESULTS: All measures showed significant
      increases in scores following smoking abstinence. The two-item MPSS measure was
      similar to the QSU-brief (eta-squared 0.41 versus 0.45, respectively), and the CR
      was only slightly lower (eta-squared 0.37). The MNWS showed the least sensitivity
      (eta-squared 0.22). Stability while still smoking was good with the exception of
      the SS which showed a significant reduction on retest. CONCLUSIONS: The ten-item
      QSU-brief is not more sensitive to abstinence or reliable than the two-item MPSS
      or a single rating of craving.

PMID- 20033134
TI  - Direct chiral determination of free amino acid enantiomers by two-dimensional
      liquid chromatography: application to control transformations in E-beam
      irradiated foodstuffs.
AB  - Changes in free amino acids content and its potential racemization in ready-to
      eat foods treated with E-beam irradiation between 1 and 8 kGy for sanitation
      purposes were studied. A simple heart cut two-dimensional high performance liquid
      chromatographic method (LC-LC) for the simultaneous enantiomeric determination of
      three pairs of amino acids used as markers (tyrosine, phenylalanine, and
      tryptophan) is presented. The proposed method involves the use of two
      chromatographs in an LC-LC achiral-chiral coupling. Amino acids and their
      decomposition products were firstly separated in a primary column (C(18)) using a
      mixture of ammonium acetate buffer (20 mM, pH 6) (94%) and methanol (6%) as the
      mobile phase. Then, a portion of each peak was transferred by heart cutting
      through a switching valve to a teicoplanin-chiral column. Methanol (90%)/water
      (10%) was used as the mobile phase. Ultraviolet detection was at 260 nm.
      Detection limits were between 0.16 and 3 mg L(-1) for each enantiomer. Recoveries
      were in the range 79-98%. The LC-LC method combined with the proposed sample
      extraction procedure is suitable for complex samples; it involves an online
      cleanup, and it prevents degradation of protein, racemization of L-enantiomers,
      and degradation of tryptophan. Under these conditions, D-amino acids were not
      found in any of the analyzed samples at detection levels of the proposed method.

PMID- 20033135
TI  - Methylene blue as an electrochemical indicator for DF508 cystic fibrosis mutation
      detection.
AB  - Cystic fibrosis is one of the most common life-shortening, childhood-onset
      inherited diseases. Among the 1,000 known cystic fibrosis-related mutations,
      DF508 is the most common, with a frequency varying between 50% and 70% according
      to geographical areas and population typology. In this work, we report the use of
      methylene blue as an electrochemical reporting agent in the discrimination of
      synthetic PCR analogue of the DF508 cystic fibrosis mutation (Mut) from the wild
      type (Wt). At optimum experimental condition, a discrimination factor between
      mutant and wild type of approximately 1.5-fold was found. The proposed assay was
      quantitative and linear in the range of 10-100 nM, exhibiting a limit of
      detection of 2.64 nM. Electrochemical studies at variable ionic strength
      conditions allowed further elucidation of the mechanism of the methylene blue
      (MB)-DNA interaction. To the best of our knowledge, this is the first report of
      detection of hybridisation solely via guanine-specific MB-DNA interaction
      simultaneously in MB solution, independent of electrostatic interaction as
      demonstrated in the ionic strength study. The introduction of formamide in the
      hybridization buffer, to improve discrimination, was also investigated. Finally,
      mutant wild type discrimination was demonstrated, at 10 nM concentration, with
      the use of a multi-sensor setup.

PMID- 20033136
TI  - Investigation of glow-discharge-induced morphology modifications on silicon
      wafers and chromium conversion coatings by AFM and rugosimetry.
AB  - The effect of radiofrequency glow-discharge sputtering on the sample surface in
      terms of modifications in the surface morphology were investigated in this work
      by using atomic force microscopy (AFM) and rugosimetry measurements. The
      influence of GD operating parameters (e.g. rf power, discharge pressure and
      sputtering time) on surface roughening was investigated using two different types
      of samples: mirror-polished and homogeneous silicon wafers and chromate
      conversion coatings (CCCs). Surface morphology changes produced by GD sputtering
      into the sample surface were carefully investigated by AFM and rugosimetry, both
      at the original sample surface and at the bottom of GD craters using different GD
      experimental conditions, such as the sputtering time (from 1 s to 20 min), rf
      forward power (20-60 W for the Si wafer and 10-60 W for the CCC), and discharge
      pressure (400-1,000 Pa for the Si wafer and 500-1000 Pa for the CCC). In the
      present study, GD-induced morphology modifications were observed after rf-GD-OES
      analysis, both for the silicon wafers and the CCC. Additionally, the changes
      observed in surface roughness after GD sputtering were found to be sample
      dependent, changing the proportion, shape and roughness of the micro-sized
      patterns and holes with the sample matrix and the GD conditions.

PMID- 20033137
TI  - Feasibility study for the rapid screening of target molecules using translational
      diffusion coefficients: diffusion-ordered NMR spectroscopy of biological toxins.
AB  - A panel of 15 biological toxins ranging between approximately 60-28,000 g/mol was
      used to evaluate the feasibility of screening aqueous samples for toxin analytes
      based on their translational diffusion coefficients, D(t). Toxin D(t) values were
      measured by pulsed-field gradient (1)H NMR spectroscopy using a bipolar pulse
      pair, longitudinal eddy current delay pulse sequence incorporating water
      suppression to achieve the maximum dynamic range for toxin signals. To collect
      data for an effective screening protocol, reference D(t) values were determined
      from five independent measurements at both 25 and 37 degrees C for all toxins in
      the panel. In the protocol, D(t) values are measured at both temperatures for a
      suspected toxin target in a sample, and for assignment as a potential toxin
      analyte, the measurements are required to fall within +/-0.25 x 10(-6) cm(2)/s of
      both reference D(t) values for at least one toxin in the panel. Only solution
      viscosity was found to influence sample D(t) measurements appreciably; however,
      the measurements are easily corrected for viscosity effects by calculating the
      D(t) value of the suspected toxin at infinite dilution. In conclusion, the
      protocol provides a rapid and effective means for screening aqueous samples for
      all toxins in the panel, narrowing toxin identification to < or = 2 possibilities
      in virtually all cases.

PMID- 20033138
TI  - A fluorescent immunochromatographic test using immunoliposomes for detecting
      microcystins and nodularins.
AB  - Microcystins (MCs), a group of cyclic heptapeptides produced by common
      cyanobacteria (blue green algae), cause both acute and chronic toxicity. Due to
      their toxicity, constant monitoring in drinking water, recreational waters as
      well as other potential exposure through ingestion of contaminated sea food, is
      very important. In this context, an immunochromatographic test (ICT) using a
      monoclonal antibody labeled with fluorescent liposomes (immunoliposomes) as
      tracer was developed, allowing a rapid and simple detection of a large number of
      MC and nodularin variants in field samples. The present ICT using immunoliposomes
      proved to be ten times more sensitive than the ICT using colloidal gold for
      labeling. To achieve quantitative measurement, this ICT was improved by including
      a stable signal on the control band allowing the expression of the results as a
      ratio of the fluorescence signals of the specific band versus the control band
      (SB/CB). Very low concentrations of MC-LR were detected in the analysis buffer
      (0.06 ng/ml), well below the guideline value of 1 ng/ml proposed by the World
      Health Organization (WHO), with a dynamic range from 0.06 to 1.5 ng/ml of MC-LR.
      This method was also validated using a hand-held commercial fluorometer (from
      ESE), providing the same performances obtained via the analysis station (from
      Kodak) used in our laboratory. Repeatability tests performed with both devices
      showed good accuracy (CV < 13%). Furthermore, quantification of MCs in natural
      samples (water bloom and Microcystis culture) was achieved using ICT, leading to
      similar results obtained via an EIA previously described. All these results
      demonstrate that this new fluorescent ICT could be used not only as a sensitive
      detection tool but also to quantify MCs in field samples.

PMID- 20033139
TI  - Precipitation and selective extraction of human serum endogenous peptides with
      analysis by quadrupole time-of-flight mass spectrometry reveals posttranslational
      modifications and low-abundance peptides.
AB  - The endogenous peptides of human serum may have regulatory functions, have been
      associated with physiological states, and their modifications may reveal some
      mechanisms of disease. In order to correlate levels of specific peptides with
      disease alongside internal standards, the polypeptides must first be reliably
      extracted and identified. Endogenous blood peptides can be effectively enriched
      by precipitation of the serum with organic solvents followed by selective
      extraction of peptides using aqueous solutions modified with organic solvents.
      Polypeptides on filter paper were assayed with Coomasie brilliant blue binding.
      The polypeptides were resolved by detergent tricine polyacrylamide
      electrophoresis and visualized by diamine silver staining. Peptides in the
      extracts were collected by C18 and analyzed by matrix-assisted laser
      desorption/ionization and liquid chromatography-electrospray ionization-tandem
      mass spectrometry (MS/MS) quadrupole time-of-flight MS/MS. Peptides were resolved
      as multiple isotopic peaks in MS mode with mass deviation of 0.1 Da or less and
      similar accuracy for fragments. The sensitivity of MS and MS/MS analysis was
      estimated to be in the picomolar range or less. The peptide composition of the
      extracts was dependent on solvent formulation. Multiple peptides from
      apolipoproteins, complement proteins, coagulation factors, and many others were
      identified by X!Tandem with high mass accuracy of peptide ions and fragments from
      collision-induced dissociation. Many previously unreported posttranslational
      modifications of peptides including phosphorylations, oxidations, glycosylations,
      and others were detected with high mass accuracy and may be of clinical
      importance. About 4,630 redundant peptides were identified with 99% confidence
      separately, and together some 1,251 distinct proteins were identified with 99%
      confidence or greater using the Paragon algorithm.

PMID- 20033140
TI  - An "off-on" fluorescence probe for chromium(III) ion determination in aqueous
      solution.
AB  - An "off-on" rhodamine-based fluorescence probe for the selective signaling of
      Cr(III) has been designed by exploiting the guest-induced structure transform
      mechanism. This system shows a sharp Cr(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 Cr(VI), Al(III), Fe(III), Cd(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
      Cr(III) concentration from 5.0 x 10(-8) to 7.0 x 10(-6) mol L(-1) with a
      detection limit of 1.6 x 10(-8) mol L(-1).

PMID- 20033141
TI  - Tetracyclines inhibit rat osteoclast formation and activity in vitro and affect
      bone turnover in young rats in vivo.
AB  - An experiment was designed to investigate whether systemic administration of
      tetracyclines (TCs) as bone fluorochrome labels could interfere with bone
      modeling in vivo and inhibit osteoclast formation and activity in vitro. Cell
      cultures of rat bone marrow macrophages revealed that TC and oxytetracycline
      inhibited osteoclastogenesis and bone resorption and stimulated apoptosis. Forty
      rats in five groups were treated with saline, calcein green, alizarin red S, TC,
      or oxytetracycline. Their tibias were used for histomorphometric analysis,
      including bone static, dynamic, and resorption parameters in the tibial proximal
      metaphysis. No significant differences in bone volume per tissue volume,
      trabecular number, trabecular thickness, trabecular separation, bone formation
      rate per bone surface, mineralizing surface, or mineral apposition rate were
      observed. TC or oxytetracycline decreased eroded surface, number of osteoclasts
      per bone perimeter, and osteoclast surface per bone surface by about 50%. The
      results demonstrated that TC and oxytetracycline inhibit rat osteoclast formation
      and activity in vitro, and histomorphometric parameters involved in bone turnover
      may be affected by the use of oxytetracycline and TC as fluorescent bone labels
      in vivo.

PMID- 20033142
TI  - Age-related changes in regional brain volume evaluated by atlas-based method.
AB  - INTRODUCTION: The effects of aging on brain volume are generally investigated
      using voxel-based morphometry (VBM) or the manually traced region-of-interest
      (ROI) method. We introduce an atlas-based method as a methodological alternative
      that calculates absolute volume as a non-biased and semi-automatic whole-brain
      technique. METHODS: We enrolled 115 healthy females (mean age, 36.7 years) and
      130 healthy males (mean age, 37.1 years). Volume data were acquired using a 1.5
      tesla magnetic resonance scanner. After spatial normalization, a lobar-based
      atlas template was applied, and the absolute volumes of the frontal, temporal,
      parietal, and occipital lobes and the sublobar and limbic areas were calculated
      bilaterally. The effects of age on regional brain volume were evaluated
      statistically. RESULTS: The volume of all ROIs declined linearly with increasing
      age. The bilateral frontal lobes showed the steepest involution. Analysis of
      variance revealed significant laterality and interaction of gender and age.
      CONCLUSION: The atlas-based method introduced in the present study has advantages
      over the manually traced ROI method in its objectivity, coverage, and time
      requirement and has an advantage over the VBM method in its computability of
      absolute volume. The results are largely in agreement with those reported
      previously, thereby reconfirming the importance of matching gender and age in
      analyzing brain disorders.

PMID- 20033143
TI  - A huge bladder calculus causing acute renal failure.
AB  - We present a 39-year-old man with repeated urinary tract infection and lower
      abdominal pain. Kidney-ureter-bladder (KUB) and IVU film showed a huge 450-g
      elliptical pelvic calculus that was surgically removed with excellent results.
      Surgical intervention by cystolithotomy or endoscopic cystolithotripsy can
      achieve satisfactory results. Bladder outlet obstruction should be treated
      simultaneously. Bladder stone is a common disease, but it is rare for such a
      calculus to be so large as to cause bilateral hydronephrosis. Close follow-up,
      however, is mandatory because the recurrence of urolithiasis is high in those
      patients with voiding problems and recurrent urinary infection. To the best of
      our knowledge, this is the largest bladder stone in a human male.

PMID- 20033144
TI  - Biological analysis of endocrine-disrupting compounds in Tunisian sewage
      treatment plants.
AB  - Endocrin-disrupting compounds (EDCs) are frequently found in wastewater treatment
      plants (WWTPs). So far, research has been mainly focused on the detection of
      estrogenic compounds and very little work has been carried out on other receptors
      activators. In this study, we used reporter cell lines, which allow detecting the
      activity of estrogen (ERalpha), androgen (AR), pregnane X (PXR), glucocorticoid
      (GR), progesterone (PR), mineralocorticoid (MR), and aryl hydrocarbon (AhR)
      receptors, to characterise the endocrine-disrupting profile of the aqueous,
      suspended particulate matter, and sludge fractions from three Tunisian WWTPs. The
      aqueous fraction exhibited estrogenic and androgenic activities. Suspended
      particulate matter and sludge extracts showed estrogenic, aryl hydrocarbon and
      pregnane X receptor activities. No GR, MR, or PR (ant) agonistic activity was
      detected in the samples, suggesting that environmental compounds present in
      sewage might have a limited spectrum of activity. By performing competition
      experiments with recombinant ERalpha, we demonstrated that the estrogenic
      activity detected in the aqueous fraction was due to EDCs with a strong affinity
      for ERalpha. Conversely, in the sludge fraction, it was linked to the presence of
      EDCs with weak affinity. Moreover, by using different incubation times, we
      determined that the EDCs present in suspended particulate matter and sludge,
      which can activate AhR, are metabolically labile compounds. Finally, we showed in
      this study that environmental compounds are mainly ER, AR, PXR, and AhR
      activators. Concerning AR and PXR ligands, we do not to know the nature of the
      molecules. Concerning ER and AhR compounds, competition experiments with
      recombinant receptor and analysis at different times of exposure of the AhR
      activation gave some indications of the compound's nature that need to be
      confirmed by chemical analysis.

PMID- 20033145
TI  - Hey bHLH factors in cardiovascular development.
AB  - The Notch pathway is now firmly established as a key signaling system for
      embryonic cardiovascular development as well as some adult pathologies in
      vertebrates. We have identified Hey bHLH transcriptional repressors as critical,
      but partly redundant transducers of these signals. Hey proteins control
      cardiomyocyte differentiation, epithelial to mesenchymal transition of
      endocardial cells, and a number of key features of arterial endothelial cells
      with corresponding defects in knockout mice. While most of the phenotypes are
      described in embryonic development, there is increasing evidence for additional
      adult pathologies. Despite the functional importance of Hey proteins little is
      still known about their molecular targets and interactions.

PMID- 20033146
TI  - A bHLH code for cardiac morphogenesis.
AB  - Cell specification and differentiation of cardiomyocytes from mesodermal
      precursors is orchestrated by epigenetic and transcriptional inputs throughout
      heart formation. Of the many transcription factor super families that play a role
      in this process, the basic Helix-loop Helix (bHLH) family of proteins is well
      represented. The bHLH protein by design allows for dimerization-both as
      homodimers and heterodimers with other proteins within the family. Although DNA
      binding is mediated via a short variable cis-element termed an E-box, it is clear
      that DNA-affinity for these elements as well as the transcriptional input
      conveyed is dictated largely by the transcriptional partners within the dimer
      complex. Dimer partner choice has a number of inputs requiring co-expression
      within a given cell nucleus and dimerization modulation by the level of protein
      present, and post-translational modifications that can both enhance or reduce
      protein-protein interactions. Due to these complex interrelationships, it has
      been difficult to identity bona-fide downstream transcriptional targets and
      define the molecular pathways regulated of bHLH factors within cardiogenesis,
      despite the clear roles suggested via loss-of-function animals models. This
      review focuses on the Hand bHLH proteins-key members of the Twist-family of bHLH
      factors. Despite over a decade of investigation, questions regarding functional
      redundancy, downstream targets, and biological role during heart specification
      and differentiation have still not been fully addressed. Our goal is to review
      what is currently known and address strategies for gaining further understanding
      of Hand/Twist gene dosage and functional redundancy relationships within the
      developing heart that may underlie congenital heart defect pathogenesis.

PMID- 20033147
TI  - Genetic origins of pediatric heart disease.
AB  - Pediatric heart disease comprises many forms of cardiovascular disease in the
      young including cardiovascular malformations (CVM), cardiomyopathies,
      vasculopathies, e.g., Marfan syndrome, and cardiac arrhythmias. CVM are an
      important component of pediatric heart disease and constitute a major portion of
      clinically significant birth defects. In the past decade, the complementary
      nature of genetic, developmental, and biochemical approaches have contributed to
      extraordinary advances in understanding the origins of pediatric heart disease.
      Results of the studies of the cardiac transcription factor, NKX2.5, illustrate
      these accomplishments and at the same time provide a forecast of the nature of
      future genetic studies to better understand the origins of pediatric heart
      disease.

PMID- 20033148
TI  - Fluoroscopically guided caudal epidural steroid injection for management of
      degenerative lumbar spinal stenosis: short-term and long-term results.
AB  - OBJECTIVE: To evaluate the short-term and long-term effects of fluoroscopically
      guided caudal epidural steroid injection (ESI) for the management of degenerative
      lumbar spinal stenosis (DLSS) and to analyze outcome predictors. MATERIALS AND
      METHODS: All patients who underwent caudal ESI in 2006 for DLSS were included in
      the study. Response was based on chart documentation (aggravated, no change,
      slightly improved, much improved, no pain). In June 2009 telephone interviews
      were conducted, using formatted questions including the North American Spine
      Society (NASS) patient satisfaction scale. For short-term and long-term effects,
      age difference was evaluated by the Mann-Whitney U test, and gender, duration of
      symptoms, level of DLSS, spondylolisthesis, and previous operations were
      evaluated by Fisher's exact test. RESULTS: Two hundred and sixteen patients
      (male:female = 75:141; mean age 69.2 years; range 48 approximately 91 years) were
      included in the study. Improvements (slightly improved, much improved, no pain)
      were seen in 185 patients (85.6%) after an initial caudal ESI and in 189 patients
      (87.5%) after a series of caudal ESIs. Half of the patients (89/179, 49.8%)
      replied positively to the NASS patient satisfaction scale (1 or 2). There were no
      significant outcome predictors for either the short-term or the long-term
      responses. CONCLUSION: Fluoroscopically guided caudal ESI was effective for the
      management of DLSS (especially central canal stenosis) with excellent short-term
      and good long-term results, without significant outcome predictors.

PMID- 20033150
TI  - Molecular imaging in cognitive impairment: the relevance of cognitive reserve,
      importance of multisite longitudinal trials and challenges of standardised
      analysis.

PMID- 20033149
TI  - The subscapularis: anatomy, injury, and imaging.
AB  - The subscapularis is the largest and most powerful of the rotator cuff muscles
      and fulfills an important role in glenohumeral movement and stability. The
      spectrum and implications of subscapularis muscle or tendon injury differ from
      injury to other rotator cuff components because of its unique structure and
      function. Diagnosing subscapularis injury is clinically difficult and assessment
      of subscapularis integrity may be limited during arthroscopy or open surgery.
      Diagnostic imaging plays an important part in diagnosing and evaluating the
      extent of subscapularis injury. The radiologist should be aware of the anatomy of
      the subscapularis, the variations in muscle or tendon injury, and the potential
      implications for treatment and prognosis.

PMID- 20033151
TI  - Syllabus for postgraduate specialisation in Nuclear Medicine : 2006/07 update.

PMID- 20033153
TI  - Use of (99m)Tc-MDP SPECT for assessment of mandibular growth: development of
      normal values.
AB  - PURPOSE: Planar scintigraphy using (99m)Tc-labeled methylene diphosphonate
      ((99m)Tc-MDP) has been established as a method for evaluating mandibular growth
      and asymmetry. However, (99m)Tc-MDP single photon emission computed tomography
      (SPECT) provides improved image contrast and quantitative capability potentially
      allowing the clinician to make a more accurate assessment of the stage of
      activity of normal and asymmetric mandibular growth. The purpose of this study
      was to utilize (99m)Tc-MDP SPECT in normal subjects to develop a standardized
      approach to imaging the mandible that could subsequently be used to evaluate
      patients with potential for mandibular growth abnormalities. METHODS: Thirty-two
      patients (22 females, 10 males, 8-25 years of age, mean of 14 years) having
      (99m)Tc-MDP bone scans (7.4 MBq/kg, maximum of 518 MBq) for indications not
      involving the head were asked to have an additional SPECT that included the
      mandibular condyles. Internal (clivus) and external (source of known activity
      included within the field of view) standards were both investigated. Two- and
      three-dimensional (2-D and 3-D) regions of interest (ROI) were drawn over each
      condyle and the clivus in a single slice containing the maximum pixel value
      within the structure. A 3-D ROI was also drawn about the external standard.
      Maximum and average pixel values within the 2-D and 3-D ROIs were recorded.
      RESULTS: Correlation analysis indicated that essentially the same information was
      obtained whether the maximum or average pixel value within a 2-D or 3-D ROI was
      used. The right to left ratio provided a parameter that can be used to assess the
      magnitude of mandibular metabolic asymmetry. Use of an external standard provides
      the potential for quantifying condylar uptake for assessment of the activity of
      mandibular growth. Normal ranges for different age groups were determined for
      condylar uptake using both internal and external standards. CONCLUSION: (99m)Tc
      MDP SPECT provides a quantitative method for assessing mandibular condylar uptake
      as a reflection of the activity of mandibular growth. The maximum pixel value of
      a 2-D ROI using external standardization and the right to left ratio of the
      condylar uptake provide the potential for quantitative evaluation of patients
      with mandibular asymmetry. These parameters will be further evaluated in an
      upcoming clinical investigation.

PMID- 20033154
TI  - PET/CT colonography: a novel non-invasive technique for assessment of extent and
      activity of ulcerative colitis.
AB  - PURPOSE: Extent of involvement and activity of ulcerative colitis (UC) is best
      evaluated by colonoscopy. Colonoscopy however carries risk during acute
      exacerbation. We investigated the utility of PET/CT colonography for assessment
      of extent and activity of UC. METHODS: Within a 1-week window, 15 patients with
      mild to moderately active UC underwent colonoscopy and PET/CT colonography 60 min
      after injection of 10 mCi of (18)F-fluorodeoxyglucose (FDG). PET activity score
      based on the amount of FDG uptake and endoscopic mucosal activity in seven
      colonic segments of each patient was recorded. The mean maximum standardized
      uptake value (SUV(max)) of seven segments was compared with activity in liver. A
      PET activity grade of 0, 1, 2 or 3 was assigned to each region depending upon
      their SUV(max) ratio (colon segment to liver). RESULTS: The extent of disease was
      left-sided colitis in five and pancolitis in ten. The mean Ulcerative Colitis
      Disease Activity Index (UCDAI) was 7.6. The number of segments involved as per
      colonoscopic evaluation and PET/CT colonography was 67 and 66, respectively.
      There was a good correlation for extent evaluation between the two modalities
      (kappa 55.3%, p = 0.02). One patient had grade 0 PET activity, nine had grade 2
      and five had grade 3 PET activity. In six patients, there was one to one
      correlation between PET activity grades with that of endoscopic grade. One
      patient showed activity in the sacroiliac joint suggesting active sacroiliitis.
      CONCLUSION: PET/CT colonography is a novel non-invasive technique for the
      assessment of extent and activity of the disease in patients with UC.

PMID- 20033155
TI  - The new FDG brain revolution: the neurovascular unit and the default network.

PMID- 20033156
TI  - Radiopharmaceuticals for positron emission tomography investigations of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a common degenerative neurological disease that is an
      increasing medical, economical, and social problem. There is evidence that a long
      "asymptomatic" phase of the disease exists where functional changes in the brain
      are present, but structural imaging for instance with magnetic resonance imaging
      remains normal. Positron emission tomography (PET) is one of the tools by which
      it is possible to explore changes in cerebral blood flow and metabolism and the
      functioning of different neurotransmitter systems. More recently, investigation
      of protein aggregations such as amyloid deposits or neurofibrillary tangles
      containing tau-protein has become possible. The purpose of this paper is to
      review the current knowledge on various (18)F- and (11)C-labelled PET tracers
      that could be used to study the pathophysiology of AD, to be used in the early or
      differential diagnosis or to be used in development of treatment and in
      monitoring of treatment effects.

PMID- 20033157
TI  - Testing the theory of immune selection in cancers that break the rules of
      transplantation.
AB  - Modification of cancer cells likely to reduce their immunogenicity, including
      loss or down-regulation of MHC molecules, is now well documented and has become
      the main support for the concept of immune surveillance. The evidence that these
      modifications, in fact, result from selection by the immune system is less clear,
      since the possibility that they may result from reorganized metabolism associated
      with proliferation or from cell de-differentiation remains. Here, we (a) survey
      old and new transplantation experiments that test the possibility of selection
      and (b) survey how transmissible tumours of dogs and Tasmanian devils provide
      naturally evolved tests of immune surveillance.

PMID- 20033159
TI  - Hawaiian residents' preferences for Miconia control program attributes using
      conjoint choice experiment and latent class analysis.
AB  - Invasive species control or eradication is an important issue. On the islands of
      Hawaii, this problem is exceedingly evident when it comes to Miconia calvescens
      (Miconia). Adequate funding is needed to control or eradicate this invasive
      plant, but with the limited amount of funding available for the fight against
      Miconia, it is important to make sure that the fund is being spent in a way that
      addresses the needs or preferences of the Hawaiian residents. Using the conjoint
      choice experiment method, we designed a survey that would measure the Hawaiian
      residents' willingness to support Miconia control program attributes. The
      attributes focused on were cost, biodiversity loss, extent of spread and soil
      erosion. Latent class approach was used to assess the surveyed population to see
      the different preferences by individual classes. The results show three different
      classes or groups of individuals with varying preferences for a control program
      of which cost and erosion were the top preferred attributes among the classes.
      These groups were defined by their socio-demographics of income, the length of
      residency and exposure to farming/gardening activities. Even with a preference
      for lower cost, a group showed willingness to pay more ($2.40) for a program that
      reduces erosion from high to low. Finally, the biodiversity attribute had very
      low consideration from a majority of the respondents showing the need for
      educating the public regarding its importance in preserving the unique
      environment in Hawaii.

PMID- 20033158
TI  - Long-term follow-up after surgical treatment of talar fractures: Twenty cases
      with an average follow-up of 7.5 years.
AB  - Displaced talar neck and body fractures are rare and serious injuries with
      important outcomes. The aim of our study was to evaluate the long-term outcomes
      of these fractures after operative treatment in our centre between 1993 and 2005.
      Displaced talar fractures have a high rate of long-term complications. This was a
      retrospective study concerning 20 patients with an average follow-up of 7.5
      years. The final follow-up examination included determination of the AHS score
      (ankle-hindfoot scale) from the American Orthopaedic Foot and Ankle Society
      (AOFAS), range of motion evaluation and radiological analysis. Mean age at the
      time of trauma was 38.8 years. This study comprised ten talar neck fractures and
      ten talar body fractures. We always used a single surgical approach and obtained
      anatomical reduction in 30% of the whole series of both groups. Four early
      complications were noted in four patients (20%). We noted no skin complications
      and the rate of consolidation was 100%. Four patients (20%) developed avascular
      necrosis of the talus, and at final follow-up seven patients (35%) had undergone
      secondary surgery. Radiographic analysis showed an osteoarthritis rate of 94% and
      a malunion rate of 59%. The mean AOFAS score was 66.9/100 and range of motion was
      systematically decreased. Contrary to undisplaced talar fractures, displaced
      talar fractures are a therapeutic challenge with many early or late
      complications. The outcome often revealed stiffness and osteoarthritis.

PMID- 20033160
TI  - Predictors of Ips confusus outbreaks during a record drought in southwestern USA:
      implications for monitoring and management.
AB  - In many ecosystems the effects of disturbance can be cryptic and disturbance may
      vary in subtle spatiotemporal ways. For instance, we know that bark beetle
      outbreaks are more frequent in temperate forests during droughts; however, we
      have little idea about why they occur in some locations and not others.
      Understanding biotic and abiotic factors promoting bark beetle outbreaks can be
      critical to predicting and responding to pest outbreaks. Here we address the
      environmental factors which are associated with Ips confusus outbreaks during the
      2002 widespread drought within the distribution range of pinyon pine woodlands in
      Arizona. We used univariate statistics to test if whether tree characteristics,
      other herbivores, stand properties, soil type, wind, and topography were
      associated with I. confusus outbreak, and logistic regression to create a
      predictive model for the outbreaks. We found that I. confusus attacks occur in
      low elevation stands on steeper slopes, where favorable winds for I. confusus
      dispersion occur. I. confusus select larger trees, in high density stands with
      understory shrubs that exhibit phenotypic traits characteristic of resistance to
      stem-boring moths. The model was highly accurate, and explained 95% of the
      variability in occurrence (98% of the absences and 95% of the presences).
      Accurate prediction of the impacts of disturbance allow us to anticipate,
      minimize or mitigate for and eventually counteract its effects, especially those
      affecting diversity and ecosystem function. Identification of outbreak risk areas
      can guide regional and national management towards the reduction of infestation
      risk and enhancing conservation of pinyon-juniper woodlands.

PMID- 20033161
TI  - Endovascular management of delayed complete graft thrombosis after endovascular
      aneurysm repair.
AB  - Graft thrombosis rates after endovascular aneurysm repair (EVAR) of abdominal
      aortic aneurysms vary widely in published series. When thrombosis does occur, it
      usually involves a single limb and occurs within 3 months of stent-graft
      insertion. If the entire endoprosthesis is thrombosed, treatment may be
      challenging because femoro-femoral crossover graft insertion is not an option and
      a greater volume of thrombus is present, thus making thrombolysis more difficult.
      We present two cases of delayed thrombosis after EVAR involving the entire stent
      graft. These were successfully treated by a combined surgical and endovascular
      technique, and patency has been maintained in both cases to date.

PMID- 20033162
TI  - Clinical application of a new indwelling catheter with a side-hole and spirally
      arranged shape-memory alloy for hepatic arterial infusion chemotherapy.
AB  - A new indwelling catheter, G-spiral (GSP), was developed for hepatic arterial
      infusion chemotherapy (HAIC) by way of an implanted catheter-port system (CPS).
      Here we evaluated its physical properties and the outcomes of its clinical use.
      The GSP vessel-fixing power and its ability to follow a guidewire were determined
      with a vascular in vitro model, and Student t test was used to determine
      statistical significance (P < 0.05). A retrospective analysis was performed to
      evaluate the technical success rate and to identify the clinical complications
      associated with radiologic CPS implantation with GSP in 65 patients with
      unresectable hepatic tumors. The mean vessel-fixing power of the GSP (14.4 g)
      significantly differed from that of a GSP with a cut shape-memory alloy (3.3 g).
      The mean resistance to following the guidewire displayed by the GSP (88.5 g) was
      significantly less than that for a 5F W-spiral (106.3 g) or 4F Cobra-type
      angiographic catheter (117.8 g). The CPS was placed successfully in 64 of 65
      cases (98.5%). Hepatic artery occlusion was observed in one case. Occlusion,
      cracking, and infection of CPS were observed in one, two, and one case,
      respectively. The GSP is a highly useful indwelling catheter that can be used for
      HAIC.

PMID- 20033163
TI  - Transradial approach for transcatheter selective superior mesenteric artery
      urokinase infusion therapy in patients with acute extensive portal and superior
      mesenteric vein thrombosis.
AB  - The purpose of this investigation was to assess the feasibility and effectiveness
      of transradial approach for transcatheter superior mesenteric artery (SMA)
      urokinase infusion therapy in patients with acute extensive portal and superior
      mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute
      extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were
      treated by transcatheter selective SMA urokinase infusion therapy by way of the
      radial artery. The mean age of the patients was 39.5 years. Through the radial
      sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of
      urokinase was performed for 5-11 days (7.1 +/- 2.5 days). Adequate
      anticoagulation was given during treatment, throughout hospitalization, and after
      discharge. Technical success was achieved in all 16 patients. Substantial
      clinical improvement was seen in these 16 patients after the procedure. Minor
      complications at the radial puncture site were observed in 5 patients, but trans
      SMA infusion therapy was not interrupted. Follow-up computed tomography scan
      before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis
      in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The
      16 patients were discharged 9-19 days (12 +/- 6.0 days) after admission. Mean
      duration of follow-up after hospital discharge was 44 +/- 18.5 months, and no
      recurrent episodes of PV-SMV thrombosis developed during that time period.
      Transradial approach for transcatheter selective SMA urokinase infusion therapy
      in addition to anticoagulation is a safe and effective therapy for the management
      of patients with acute extensive PV-SMV thrombosis.

PMID- 20033164
TI  - Transbrachial access for radiologic manipulation of problematic central venous
      catheters in a pediatric population.
AB  - A transfemoral venous approach is the current standard for accessing
      malpositioned and fractured central venous catheters (CVCs). The purpose of this
      study was (1) to describe a transbrachial approach for correction and (2) to
      assess the success and failure of this method in a pediatric population. A 12
      year retrospective review of all patients referred for correction of
      malpositioned, retained, and fractured CVCs was conducted. Based on the
      performing interventionalist's preference, transbrachial or transfemoral venous
      sheaths where placed under ultrasonographic guidance. Diagnostic angiographic
      catheters and snares were used to manipulate the catheters. Patients who
      underwent the transfemoral approach received postprocedural monitoring for 4
      hours, whereas patients who underwent the transbrachial approach were allowed
      unrestricted activity immediately after hemostasis was obtained. Technical
      success of malpositioned lines was defined (1) by final position in the superior
      vena cava or at the cavoatrial junction on postprocedural imaging or (2) by
      successful removal of retained catheter fragments, if present. Transbrachial
      approach was used for access in 11 patients. Problematic lines included
      malpositioned (n = 10) and retained (n = 1) lines. The ipsilateral arm was used
      for transbrachial entry in 7 patients. Initial use of angiographic catheters was
      attempted in 7 cases, of which 4 were successful. All 3 unsuccessful cases had
      tips positioned in the contralateral brachiocephalic vein, and these were
      successfully repositioned using snares. A combination of snares and angiographic
      catheters was used in 2 cases. Snares were used for all other cases. Technical
      success by way of the transbrachial approach was observed in all cases.
      Periprocedural follow-up demonstrated no immediate complications. We conclude
      that the transbrachial approach is a suitable alternative to the transfemoral
      approach for catheter tip position correction. Tip malposition in the
      contralateral brachiocephalic vein suggests higher rate of conversion to use of
      snare devices.

PMID- 20033165
TI  - Impact of stent design on in-stent stenosis in a rabbit iliac artery model.
AB  - The purpose of this study was to evaluate the impact of stent design on in-stent
      stenosis in rabbit iliac arteries. Four different types of stent were implanted
      in rabbit iliac arteries, being different in stent design (crown or wave) and
      strut thickness (50 or 100 microm). Ten stents of each type were implanted. Each
      animal received one crown and one wave stent with the same strut thickness.
      Follow-up was either 12 weeks (n = 10 rabbits) or 24 weeks (n = 10 rabbits).
      Primary study end points were angiographic and microscopic in-stent stenosis.
      Secondary study end points were vessel injury, vascular inflammation, and stent
      endothelialization. Average stent diameter, relative stent overdilation, average
      and minimal luminal diameter, and relative average and maximum luminal loss were
      not significantly different. However, a trend to higher relative stent
      overdilation was recognized in crown stents compared to wave stents. A trend
      toward higher average and minimal luminal diameter and lower relative average and
      maximum luminal loss was recognized in crown stents compared to wave stents with
      a strut thickness of 100 microm. Neointimal height, relative luminal area
      stenosis, injury score, inflammation score, and endothelialization score were not
      significantly different. However, a trend toward higher neointimal height was
      recognized in crown stents compared to wave stents with a strut thickness of 50
      microm and a follow-up of 24 weeks. In conclusion, in this study, crown stents
      seem to trigger neointima. However, the optimized radial force might equalize the
      theoretically higher tendency for restenosis in crown stents. In this context,
      also more favorable positive remodeling in crown stents could be important.

PMID- 20033166
TI  - The role of patellar tendon morphometry on anterior knee pain.
AB  - PURPOSE: To investigate the morphometry of patellar tendon with magnetic
      resonance imaging (MRI) and to reveal the relation between patellar tendon
      properties and anterior knee pain (AnKP). METHODS: Twenty-three patients with
      AnKP and nine healthy individuals were included in the study. Patients with knee
      anomaly that may cause AnKP were excluded from the study. The patellar tendon
      examination was performed on sagittal and coronal sections of MRI. Freehand
      technique was used to frame the area of tendon and calculations were done by
      generic software. RESULTS: There were 23 patients in AnKP (+) and 9 individuals
      in AnKP (-) group. The morphometric results were not different among groups (p =
      0.2). Higher body mass index was correlated with increased patellar tendon
      surface area in women (R (2) = 0.37). CONCLUSION: Patellar tendon length,
      thickness and surface area do not seem as a significant parameter to explain the
      aetiology of AnKP. Given the well-defined role of patellar tendon to support knee
      kinetics, the clinical value of tendon morphometry is to be determined.

PMID- 20033167
TI  - The anatomy of the cricoid pressure unit.

PMID- 20033168
TI  - MRI of the median nerve and median artery in the carpal tunnel: prevalence of
      their anatomical variations and clinical significance.
AB  - OBJECTIVE: Anatomical variations of the median nerve and the persistent median
      artery (PMA) in the carpal tunnel (CT) are important to understand for their
      clinical and surgical significance. The aim of this cohort retrospective study
      was to investigate the prevalence of aberrant median nerve branches and
      persistent median artery in the CT in a selected population using magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: MR wrist images of 194 patients,
      77 males and 117 females, aged 12-80 years were randomly selected and retrieved
      from our clinical and radiology data base. The MR examinations were performed
      using either 1.5-T or 3.0-T magnet using a cylindrical receive-transmit wrist
      coil for all cases. The course of the bifurcation of the median nerve was
      followed on axial T2-weighted and axial proton density fat saturated images and
      classified as either proximal, within, or distal to the CT. The flexor
      retinaculum proximally and the metacarpal bases were used as anatomic landmarks
      to subdivide these three categories. In addition, the median artery was searched
      in order to assess the prevalence of its presence inside the CT. A total of 194
      wrists were analyzed by two musculoskeletal-trained radiologists. They were
      blinded on the population age, gender, and the sides of the wrists. Agreement was
      reached by consensus. RESULTS: Among the 194 wrists, there was bifurcation of the
      nerve proximal to the CT in 12 (6.1%) wrists. There was nerve bifurcation within
      the CT in 36 (18%) wrists. Nerve bifurcation distal to the CT was more frequently
      observed, occurring in 147 (75%) wrists. Only one nerve trifurcation was seen
      within the CT. There was no gender predominance for the nerve bifurcation within
      the tunnel. There were 107 right wrists and 87 left wrists. On the right side,
      bifurcation of the nerve within the CT was seen in 21 (19.6%) wrists; and on the
      left side bifurcation of the nerve was present in 15 (17.2%) wrists.
      Statistically, we found no significant difference in the prevalence of the bifid
      nerve within the tunnel in the subgroups based on age, gender, or side of the
      wrists. A persistent median artery (PMA) within the tunnel was observed in 21
      (11%) wrists--10 males and 11 females. Of these, four (19%) cases were presented
      with coexistent PMA and bifid median nerve within the tunnel. Statistically, we
      found that the two variations are not independent traits, and their covariance is
      not null. CONCLUSION: There was a high prevalence of bifid median nerve (19%) and
      PMA (11%) within the tunnel regardless of gender or age. The PMA was more
      frequent on the left side.

PMID- 20033169
TI  - Diversity of Bacillus thuringiensis isolated from Western Ghats of Tamil Nadu
      State, India.
AB  - The Western Ghats of India is the one of the world's 10 "Hottest biodiversity
      hotspots" that runs along the western part of India through four states including
      Tamil Nadu. The only biodiversity reserve in the Western Ghats is the Nilgiri
      biosphere located in the Tamil Nadu state. In the present study, 525 soil samples
      were collected from all the 14 different divisions of the Western Ghats in Tamil
      Nadu state, India. A total of 316 new isolates of Bacillus thuringiensis (Bt)
      that produce parasporal crystalline inclusions were isolated from 525 soil
      samples. Seven different types of crystalline inclusions were observed in the 316
      new isolates of Bt. Cuboidal inclusion was predominantly present in 26.9% of the
      Bt isolates when compared to other shapes. Further characterization of 70 of the
      316 Bt isolates for crystal protein profile through SDS-PAGE revealed six
      different types of crystal protein profile viz., 135 and 65, 135, 95, 65, 43, and
      30 kDa crystal proteins. Variation in the mass of crystal protein(s) purified
      from the isolates of Bt revealed molecular diversity of this bacterium prevalent
      in the Western Ghats of Tamil Nadu, India.

PMID- 20033170
TI  - Comparative evaluation of five culture media with triplex PCR assay for detection
      of methicillin-resistant Staphylococcus aureus.
AB  - The emergence of methicillin-resistant Staphylococcus aureus (MRSA) is
      responsible for nosocomial and community-acquired infections. Hence, rapid and
      accurate laboratory diagnosis of MRSA is a vital constituent of control measures.
      The present study evaluated five different methods for the identification of
      MRSA. A total of 207 S. aureus clinical isolates that consisted of 89 MRSA and
      118 methicillin-susceptible S. aureus (MSSA) strains confirmed by PCR were
      tested. MRSA strains were evaluated by five different methods: chromogenic MRSA
      agar (CMRSA), oxacillin resistance screening agar base (ORSAB), mannitol salt
      oxacillin agar (MSO), mannitol salt cefoxitin agar with two different
      concentrations of cefoxitin [4 microg/ml (MSC-4) and 6 microg/ml (MSC-6)]. The
      results of the different methods were compared to mecA PCR as the gold standard.
      MSC-6 showed only six false-positive MRSA in comparison with PCR. The
      sensitivities and specificities of MSC-6, MSC-4, MSO-4, ORSAB, and CMRSA were as
      follows: 98.9/94.9%, 100/83.1%, 89.9/87.3%, 97.8/96.6%, and 95.5/94.9%,
      respectively. In comparison with PCR, it was found that both MSC-6 and ORSAB were
      relatively the least expensive screening tests ($0.70 and $1.00, respectively).
      In conclusion, all methods were comparable, but MSC-6 was the least expensive
      medium for MRSA screening.

PMID- 20033171
TI  - Functional analyses of Escherichia coli MutS-beta clamp interaction in vitro and
      in vivo.
AB  - Escherichia coli MutS is a highly conserved mismatch repair (MMR) protein that
      plays a key role in recognizing DNA mismatches and the early steps of MMR.
      Previous studies revealed an interaction between MutS and the replicative protein
      beta clamp, but it remains unclear whether the interaction functions during the
      process of MMR. In order to provide insight into the significance of this
      interaction, Far Western, Surface plasmon resonance and cell survival/mutagenesis
      assays were used to determine its possible influences on the in vitro and in vivo
      properties of MutS. The results show that a quintuple mutation of MutS residues
      812-816 (MutS(betaC)), or single alanine substitution mutation of MutS residues
      M813 or L815 completely blocks binding of MutS to beta clamp. Wild type beta
      clamp interferes with DNA binding by MutS. When treated with the base analog 2
      aminopurine, MutS(betaC) confers more mutations and less cellular growth rate in
      the mutS-deficient strain than the wild type MutS. These data indicate that the
      MutS-beta interaction has functional consequences during MMR in E. coli.

PMID- 20033172
TI  - K30, H150, and H168 are essential residues for coordinating pyridoxal 5'
      phosphate of O-acetylserine sulfhydrylase from Acidithiobacillus ferrooxidans.
AB  - O-acetylserine sulfhydrylase (OASS) is a key enzyme involved in the pathway of
      the cysteine biosynthesis. The gene of OASS from Acidithiobacillus ferrooxidans
      ATCC 23270 was cloned and expressed in E. coli, the soluble protein was purified
      by one-step affinity chromatography to apparent homogeneity. Colors and UV-vis
      scanning results of the recombinant protein confirmed that it was a pyridoxal 5'
      phosphate (PLP)-containing protein. Sequence alignment and site-directed mutation
      of the enzyme revealed that the cofactor PLP is covalently bound in Schiff base
      linkage with K30, as well as the two residues H150 and H168 were the crucial
      residues for PLP binding and stabilization.

PMID- 20033173
TI  - Effects of extremely low-frequency electromagnetic fields on Helicobacter pylori
      biofilm.
AB  - The aim of this work was to investigate the effects of exposure to extremely low
      frequency electromagnetic fields (ELF-EMF) both on biofilm formation and on
      mature biofilm of Helicobacter pylori. Bacterial cultures and 2-day-old biofilm
      of H. pylori ATCC 43629 were exposed to ELF-EMF (50 Hz frequency-1 mT intensity)
      for 2 days to assess their effect on the cell adhesion and on the mature biofilm
      detachment, respectively. All the exposed cultures and the respective sham
      exposed controls were studied for: the cell viability status, the cell
      morphological analysis, the biofilm mass measurement, the genotypic profile, and
      the luxS and amiA gene expression. The ELF-EMF acted on the bacterial population
      during the biofilm formation displaying significant differences in cell
      viability, as well as, in morphotypes measured by the prevalence of spiral forms
      (58.41%) in respect to the controls (33.14%), whereas, on mature biofilm, no
      significant differences were found when compared to the controls. The measurement
      of biofilm cell mass was significantly reduced in exposed cultures in both
      examined experimental conditions. No changes in DNA patterns were recorded,
      whereas a modulation in amiA gene expression was detected. An exposure to ELF-EMF
      of H. pylori biofilm induces phenotypic changes on adhering bacteria and
      decreases the cell adhesion unbalancing the bacterial population therefore
      reducing the H. pylori capability to protect itself.

PMID- 20033174
TI  - A differential game theoretical analysis of mechanistic models for
      territoriality.
AB  - In this paper, elements of differential game theory are used to analyze a
      spatially explicit home range model for interacting wolf packs when movement
      behavior is uncertain. The model consists of a system of partial differential
      equations whose parameters reflect the movement behavior of individuals within
      each pack and whose steady-state solutions describe the patterns of space-use
      associated to each pack. By controlling the behavioral parameters in a spatially
      dynamic fashion, packs adjust their patterns of movement so as to find a Nash
      optimal balance between spreading their territory and avoiding conflict with
      hostile neighbors. On the mathematical side, we show that solving a nonzero-sum
      differential game corresponds to finding a non-invasible function-valued trait.
      From the ecological standpoint, when movement behavior is uncertain, the
      resulting evolutionarily stable equilibrium gives rise to a buffer-zone, or a no
      wolf's land where deer are known to find refuge.

PMID- 20033175
TI  - Digital breast tomosynthesis versus digital mammography: a clinical performance
      study.
AB  - OBJECTIVE: To compare the clinical performance of digital breast tomosynthesis
      (DBT) with that of full-field digital mammography (FFDM) in a diagnostic
      population. METHODS: The study enrolled 200 consenting women who had at least one
      breast lesion discovered by mammography and/or ultrasound classified as doubtful
      or suspicious or probably malignant. They underwent tomosynthesis in one view
      [mediolateral oblique (MLO)] of both breasts at a dose comparable to that of
      standard screen-film mammography in two views [craniocaudal (CC) and MLO]. Images
      were rated by six breast radiologists using the BIRADS score. Ratings were
      compared with the truth established according to the standard of care and a
      multiple-reader multiple-case (MRMC) receiver-operating characteristic (ROC)
      analysis was performed. Clinical performance of DBT compared with that of FFDM
      was evaluated in terms of the difference between areas under ROC curves (AUCs)
      for BIRADS scores. RESULTS: Overall clinical performance with DBT and FFDM for
      malignant versus all other cases was not significantly different (AUCs 0.851 vs
      0.836, p = 0.645). The lower limit of the 95% CI or the difference between DBT
      and FFDM AUCs was -4.9%. CONCLUSION: Clinical performance of tomosynthesis in one
      view at the same total dose as standard screen-film mammography is not inferior
      to digital mammography in two views.

PMID- 20033176
TI  - Are there any differences in acute adverse reactions among five low-osmolar non
      ionic iodinated contrast media?
AB  - OBJECTIVES: The differences regarding adverse reactions in different low-osmolar
      non-ionic contrast media had not been investigated previously. Thus, the aims of
      this study were to identify differences in the incidence of adverse reactions in
      five different low-osmolar non-ionic contrast media. METHODS: We prospectively
      recorded all adverse events associated with five different low-osmolar non-ionic
      contrast media used in 8,931 consecutive patients for CT. Patients were randomly
      assigned to five groups: iomeprol 300 mgI/ml, iopamidol 300 mgI/ml, iohexol 300
      mgI/ml, iopromide 300 mgI/ml and ioversol 320 mgI/ml. RESULTS: Adverse events
      were observed in 241 patients (2.7%). The incidence of acute adverse reactions
      was significantly higher in the following groups: (1) iomeprol (3.9%) and
      iopromide (3.5%) groups, (2) patients aged 59 years or less (4.5%) compared with
      those aged 60 years or over (1.9%), (3) the first period (3.5%) compared with the
      late period (2.3%), (4) those with a past history of adverse reactions to
      contrast media (11.2%), and (5) patients receiving contrast media for the first
      time (3.3%) compared with those had received it previously (2.0%). CONCLUSION:
      The incidence of acute adverse reactions may be reduced in younger patients by
      using iopamidol, iohexol and ioversol.

PMID- 20033177
TI  - The use of covered stents for the endovascular treatment of extracranial internal
      carotid artery stenosis: a prospective study with a 5-year follow-up.
AB  - OBJECTIVES: To evaluate the safety and feasibility of the use of covered stents
      for the treatment of extracranial carotid artery stenosis caused by highly
      embologenic plaques, and to study the long-term outcome of patients receiving
      such covered stents. METHODS: Between 2002 and 2007, 46 patients (63%
      symptomatic, 78.3% male, 67 +/- 8.6 years old) with internal carotid artery
      stenosis caused by embologenic plaques or restenosis were treated with self
      expanding covered stents (Symbiot, Boston Scientific). Pre-dilatation or
      protecting devices were not used. Post-dilatation was applied in every patient.
      Each patient was followed long-term. The outcome measures were the occurrence of
      neurological events, and the development of in-stent restenosis, as detected by
      clinical examination and duplex ultrasound. RESULTS: The technical success rate
      of stenting was 100%. There were no neurological complications in the peri
      procedural period. The mean follow-up period was 34.3 +/- 27.7 months (the rate
      of patients lost to follow-up was 15.2%) during which no stroke or stroke-related
      deaths occurred. Restenosis was detected in 3 patients (6.5%). CONCLUSION:
      Covered stents provide efficient peri- and post-procedural protection against
      neurological complications due to embolisation from high-risk plaques during
      carotid artery stenting. Restenosis of covered stents appears to be infrequent
      during long-term follow-up.

PMID- 20033178
TI  - Contrast-enhanced ultrasound in the characterisation of breast masses: utility of
      quantitative analysis in comparison with MRI.
AB  - OBJECTIVE: To evaluate the reliability of contrast-enhanced ultrasound
      quantitative analysis (CE-US) in characterizing breast lesions, in comparison
      with MRI. MATERIALS: Thirty-nine patients with breast lesions BI-RADS 3-5 at US
      or mammography underwent CE-US and MRI. All lesions underwent histological and
      quantitative enhancement evaluation with both imaging methods. B-mode US,
      colour/power Doppler US and CE-US were used; an amplitude and phase modulation
      technique (CPS) read the signals produced by microbubbles and dedicated software
      produced the following parameters on time/intensity (T/I) curves: peak %, time to
      peak (TTP), mean transit time (MTT), regional blood volume (RBV) and regional
      blood flow (RBF). Student's t test was used to calculate the diagnostic accuracy
      of CE-US parameters compared with histological results. MRI (1.5 T) was performed
      before and after bolus gadolinium enhancement. Time/intensity curves were
      generated for all nodules and Fischer's multimodal score was used to classify
      them. RESULTS: Pathology showed 43 nodules (11 benign; 32 malignant). Peak and
      RBF were the most significant parameters in differential diagnosis, with p values
      of 0.02 and 0.004, respectively. Positive predictive value (PPV) of CE-US
      evaluation was 91%, negative predictive value (NPV) was 73% with a high
      concordance index (k = 0.59) with MRI. CONCLUSIONS: CE-US quantitative analysis
      offers an objective and reproducible assessment of lesion vascularisation, with
      good correlation with the results of MRI.

PMID- 20033179
TI  - RECIST revised: implications for the radiologist. A review article on the
      modified RECIST guideline.
AB  - The purpose of this review article is to familiarize radiologists with the
      recently revised Response Evaluation Criteria in Solid Tumours (RECIST), used in
      many anticancer drug trials to assess response and progression rate. The most
      important modifications are: a reduction in the maximum number of target lesions
      from ten to five, with a maximum of two per organ, with a longest diameter of at
      least 10 mm; in lymph nodes (LNs) the short axis rather than the long axis should
      be measured, with normal LN measuring <10 mm, non-target LN >or=10 mm but <15 mm
      and target LN >or=15 mm; osteolytic lesions with a soft tissue component and
      cystic tumours may serve as target lesions; an additional requirement for
      progressive disease (PD) of target lesions is not only a >or=20% increase in the
      sum of the longest diameter (SLD) from the nadir but also a >or=5 mm absolute
      increase in the SLD (the other response categories of target lesion are
      unchanged); PD of non-target lesions can only be applied if the increase in non
      target lesions is representative of change in overall tumour burden; detailed
      imaging guidelines. Alternative response criteria in patients with hepatocellular
      carcinoma and gastrointestinal stromal tumours are discussed.

PMID- 20033180
TI  - Polyp measurement based on CT colonography and colonoscopy: variability and
      systematic differences.
AB  - OBJECTIVE: To assess the variability and systematic differences in polyp
      measurements on optical colonoscopy and CT colonography. MATERIALS:
      Gastroenterologists measured 51 polyps by visual estimation, forceps comparison
      and linear probe. CT colonography observers randomly assessed polyp size two
      dimensionally (abdominal and intermediate window) and three-dimensionally
      (manually and semi-automatically). Linear mixed models were used to assess the
      variability and systematic differences between CT colonography and optical
      colonoscopy techniques. RESULTS: The variability of forceps and linear probe
      measurements was comparable and both showed less variability than measurement by
      visual assessment. Measurements by linear probe were 0.7 mm smaller than
      measurements by visual assessment or by forceps. The variability of all CT
      colonography techniques was lower than for measurements by forceps or visual
      assessment and sometimes lower (only 2D intermediate window and manual 3D)
      compared with measurements by linear probe. All CT colonography measurements
      judged polyps to be larger than optical colonoscopy, with differences ranging
      from 0.7 to 2.3 mm. CONCLUSION: A linear probe does not reduce the measurement
      variability of endoscopists compared with the forceps. Measurement differences
      between observers on CT colonography were usually smaller than at optical
      colonoscopy. Polyps appeared larger when using various CT colonography techniques
      than when measured during optical colonoscopy.

PMID- 20033181
TI  - Systolic acquisition of coronary dual-source computed tomography angiography:
      feasibility in an unselected patient population.
AB  - OBJECTIVE: To determine the practicability and potential dose saving of an
      imaging algorithm incorporating a pulsing scheme applying systolic data
      acquisition at heart rates >75 beats per minute (bpm). METHODS: Patients
      clinically referred for coronary computed tomography angiography (CTA) underwent
      cardiac CTA using either a diastolic pulsing window (30-70%) or a narrow systolic
      pulsing window (150 ms at 300 ms). Independent investigators retrospectively
      determined image quality (1, excellent, to 5, unreadable) and derived effective
      radiation exposure. RESULTS: Among all 101 subjects (62 +/- 2 years, 59% male)
      the predicted decrease in the best reconstruction interval for diastolic phases
      was 12 ms per 1 bpm [95% confidence interval (CI): -13.5 to -11.2] and -1.9 ms
      for systolic phases (95% CI: -3.2 to -0.62, p = 0.004), independent of age,
      gender and body mass index (BMI). The systolic pulsing strategy in 47 subjects
      (23 subjects >75 bpm) resulted in significantly lower radiation exposure (4.97 +/
      2.3 vs 9.38 +/- 5.5 mSv, p < 0.001 for systolic versus diastolic, respectively),
      whereas there was no difference with respect to image quality or heart rate (p =
      0.65 and p = 0.74, respectively). CONCLUSIONS: Our results suggest that a
      systolic window for tube current modulation in subjects with higher heart rates
      represents a reliable tool to ensure high image quality at significantly lower
      dose in patients undergoing routine cardiac CTA.

PMID- 20033182
TI  - Divergent patterns of breakpoint reuse in Muroid rodents.
AB  - Multiple Genome Rearrangement (MGR) analysis was used to define the trajectory
      and pattern of chromosome rearrangement within muroid rodents. MGR was applied
      using 107 chromosome homologies between Mus, Rattus, Peromyscus, the muroid
      sister taxon Cricetulus griseus, and Sciurus carolinensis as a non-Muroidea
      outgroup, with specific attention paid to breakpoint reuse and centromere
      evolution. This analysis revealed a high level of chromosome breakpoint
      conservation between Rattus and Peromyscus and indicated that the chromosomes of
      Mus are highly derived. This analysis identified several conserved evolutionary
      breakpoints that have been reused multiple times during karyotypic evolution in
      rodents. Our data demonstrate a high level of reuse of breakpoints among muroid
      rodents, further supporting the "Fragile Breakage Model" of chromosome evolution.
      We provide the first analysis of rodent centromeres with respect to evolutionary
      breakpoints. By analyzing closely related rodent species we were able to clarify
      muroid rodent karyotypic evolution. We were also able to derive several high
      resolution ancestral karyotypes and identify rearrangements specific to various
      stages of Muroidea evolution. These data were useful in further characterizing
      lineage-specific modes of chromosome evolution.

PMID- 20033183
TI  - A method for mapping intralocus interactions influencing excessive alcohol
      drinking.
AB  - Excessive alcohol (ethanol) consumption is the hallmark of alcohol use disorders.
      The F1 hybrid cross between the C57BL/6J (B6) and FVB/NJ (FVB) inbred mouse
      strains consumes more ethanol than either progenitor strain. The purpose of this
      study was to utilize ethanol-drinking data and genetic information to map genes
      that result in overdominant (or heterotic) ethanol drinking. About 600 B6 x FVB
      F2 mice, half of each sex, were tested for ethanol intake and preference in a 24
      h, two-bottle water versus ethanol choice procedure, with ascending ethanol
      concentrations. They were then tested for ethanol intake in a Drinking in the
      Dark (DID) procedure, first when there was no water choice and then when ethanol
      was offered versus water. DNA samples were obtained and genome-wide QTL analyses
      were performed to search for single QTLs (both additive and dominance effects)
      and interactions between pairs of QTLs, or epistasis. On average, F2 mice
      consumed excessive amounts of ethanol in the 24-h choice procedure, consistent
      with high levels of consumption seen in the F1 cross. Consumption in the DID
      procedure was similar or higher than amounts reported previously for the B6
      progenitor. QTLs resulting in heightened consumption in heterozygous compared to
      homozygous animals were found on Chrs 11, 15, and 16 for 24-h choice 30% ethanol
      consumption, and on Chr 11 for DID. No evidence was found for epistasis between
      any pair of significant or suggestive QTLs. This indicates that the hybrid
      overdominance is due to intralocus interactions at the level of individual QTL.

PMID- 20033184
TI  - Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 ( 416insG ) mice.
AB  - A new spontaneous mouse mutant was characterized by closed eyelids at weaning and
      without apparent eyes (provisional gene name, eyeless; provisional gene symbol,
      eyl). The mutation follows a recessive pattern of inheritance and was mapped to
      the region of chromosome 19 containing Pitx3. Genetic complementation tests using
      Pitx3 ( ak/+ ) mice confirmed eyl as a new allele of Pitx3 (Pitx3 ( eyl )).
      Sequencing of the Pitx3 gene in eyl mutants identified an inserted G after cDNA
      position 416 (416insG; exon 4). The shifted open reading frame is predicted to
      result in a hybrid protein still containing the Pitx3 homeobox, but followed by
      121 new amino acids. The novel Pitx3 ( eyl/eyl ) mutants expressed
      ophthalmological and brain defects similar to Pitx3 ( ak/ak ) mice:
      microphthalmia or anophthalmia and loss of dopamine neurons of the substantia
      nigra. In addition, we observed in the homozygous eyeless mutants increased
      extramedullary hematopoiesis in the spleen, frequently liver steatosis, and
      reduced body weight. There were also several behavioral changes in the homozygous
      mutants, including reduced forelimb grip strength and increased nociception. In
      addition to these alterations in both sexes, we observed in female Pitx3 (
      eyl/eyl ) mice increased anxiety-related behavior, reduced locomotor activity,
      reduced object exploration, and increased social contacts; however, we observed
      decreased anxiety-related behavior and increased arousal in males. Most of these
      defects identified in the new Pitx3 mutation are observed in Parkinson patients,
      making the Pitx3 ( eyl ) mutant a valuable new model. It is the first mouse
      mutant carrying a point mutation within the coding region of Pitx3.

PMID- 20033185
TI  - Periprostatic fat measured on computed tomography as a marker for prostate cancer
      aggressiveness.
AB  - OBJECTIVE: Several reports found that obesity was associated with prostate cancer
      (PC) aggressiveness among men treated with radical prostatectomy or radiotherapy.
      Studies concerning this issue have basically relied on body mass index (BMI), as
      a marker for general obesity. Because visceral fat is the most metabolic active
      fat, we sought to evaluate if periprostatic fat measured on a computed tomography
      (CT) is a better marker than BMI to predict PC aggressiveness in a Dutch
      population who underwent brachytherapy for localized PC. PATIENTS AND METHODS: Of
      the 902 patients who underwent brachytherapy, 725 CT scans were available.
      Subcutaneous fat thickness (CFT), periprostatic fat area (cm(2)) and fat-density
      (%) were determined on the CT scan. Patients were stratified into three groups:
      <25, 25-75 and >75 percentile of the fat-density. Associations between the three
      fat-density subgroups and BMI and PC aggressiveness were examined. RESULTS: 237
      patients were classified as having normal weight (37.2%), 320 as overweight
      (50.2%) and 80 as obese (12.6%). There was a strong significant association
      between BMI and fat-density and CFT. The strongest correlation was seen between
      BMI and CFT (Pearson r coefficient = 0.71). Logistic regression analysis revealed
      no statistically significant association between the different fat measurements
      and the risk of having a high-risk disease. CONCLUSIONS: Periprostatic fat and
      fat-density as measured with CT were not correlated with PC aggressiveness in
      patients receiving brachytherapy. However, 31% of the patients with a normal BMI
      had a fat-density of >75 percentile of the periprostatic fat-density.

PMID- 20033186
TI  - Richard Bright (1789-1858) and his contributions to the understanding of
      hydrocephalus.

PMID- 20033187
TI  - Pathomechanisms and treatment of pediatric aneurysms.
AB  - Pediatric aneurysms are rare diseases distinct from classical adult aneurysms and
      therefore require different treatment strategies. Apart from saccular aneurysms
      that are more commonly found in older children, three major pathomechanisms may
      be encountered: trauma, infection, and dissection. The posterior circulation and
      more distal locations are more commonly encountered in children compared to
      adults, and there is an overall male predominance. Clinical findings are not only
      confined to subarachnoid hemorrhage but may also comprise mass effects, headaches
      or neurological deficits. In traumatic aneurysms, the skull base and distal
      anterior communicating artery are commonly affected, and the hemorrhage occurs
      often delayed (2-4 weeks following the initial trauma). Infectious aneurysms are
      mostly bacterial in origin, and hemorrhage occurs early after a septic embolic
      shower. Dissecting aneurysms are the most often encountered aneurysm type in
      children and can lead to mass effect, hemorrhage, or ischemia depending on the
      fate of the intramural hematoma. Treatment strategies in pediatric aneurysms
      include endosaccular coil treatment only for the "classical berry-type"
      aneurysms; in the other instances, parent vessel occlusion, flow reversal,
      surgical options, or a combined treatment with bypass and parent vessel occlusion
      have to be contemplated.

PMID- 20033188
TI  - XRCC1 polymorphisms and risk of colorectal cancer: a meta-analysis.
AB  - PURPOSE: Previous studies investigating the association between X-ray repair
      cross-complementation group 1 (XRCC1) polymorphisms and colorectal cancer (CRC)
      risk has provided inconsistent results. The aim of our study was to clarify the
      effects of XRCC1variants on CRC risk. MATERIALS AND METHODS: We conducted
      searches of the published literature in PubMed, Embase, and CBM databases up to
      July 6, 2009. Meta-analysis was performed by critically reviewing 14 studies with
      a total of 2,776 CRC cases and 4,402 controls on Arg399Gln polymorphism, four
      studies with a total of 931 CRC cases and 1,547 controls on Arg280His
      polymorphism, and nine studies with a total of 1,709 CRC cases and 3,233 controls
      on Arg194Trp polymorphism, respectively. Statistical analysis was performed with
      the software programs Review Manager (version 5.0.10) and STATA (version 9.2).
      RESULTS: No significant association between Arg399Gln polymorphism and CRC risk
      was observed in both total population analyses and subgroup analyses based on
      ethnicity (OR(Co-dominant model) = 1.04, 95% CI 0.74-1.45, P (OR) = 0.82;
      OR(Dominant model) = 1.02, 95% CI 0.80-1.30, P (OR) = 0.88; OR (Recessive model)
      = 1.04, 95% CI 0.81-1.34, P (OR) = 0.78). Arg280His polymorphism also had no
      significant association with CRC risk (OR(Co-dominant model) = 0.85, 95% CI 0.32
      2.31, P (OR) = 0.76; OR(Dominant model) = 1.11, 95% CI 0.87-1.40, P (OR) = 0.40;
      OR(Recessive model) = 0.85, 95% CI 0.32-2.31, P (OR) = 0.75). Besides, there was
      also no evidence of association between Arg194Trp polymorphism and CRC risk
      (OR(Co-dominant model) = 1.43, 95% CI 0.83-2.48, P (OR) = 0.20; OR(Dominant
      model) = 1.14, 95% CI 0.87-1.51, P (OR) = 0.34; OR(Recessive model) = 1.32, 95%
      CI 0.82-2.13, P (OR) = 0.25). CONCLUSIONS: No association is found between the
      polymorphisms in XRCC1 (Arg399Gln, Arg280His, and Arg194Trp) and risk of
      colorectal cancer.

PMID- 20033189
TI  - HO-1 gene overexpression enhances the beneficial effects of superparamagnetic
      iron oxide labeled bone marrow stromal cells transplantation in swine hearts
      underwent ischemia/reperfusion: an MRI study.
AB  - To determine the effect of intracoronary transfer of superparamagnetic iron oxide
      (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells
      (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was
      assayed and supernatant cytokine concentrations were measured in BMSCs that
      underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD
      occlusion followed by 1 h reperfusion were randomly allocated to receive
      intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with
      pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1
      hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI
      and postmortem histological analysis were made at 1 week or 3 months thereafter.
      Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant
      VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO
      1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial
      expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs
      group at 1 week post transplantation (all p < 0.05). Signal voids induced by the
      SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but
      not at 3 months post transplantation and the extent of the hypointense signal was
      the highest in HO-1-BMSCs group, and histological analysis showed that signal
      voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs.
      Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1
      BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the
      beneficial effects of BMSCs on improving cardiac function in this model.

PMID- 20033190
TI  - Choroid plexus: biology and pathology.
AB  - The choroid plexus is an epithelial-endothelial vascular convolute within the
      ventricular system of the vertebrate brain. It consists of epithelial cells,
      fenestrated blood vessels, and the stroma, dependent on various physiological or
      pathological conditions, which may contain fibroblasts, mast cells, macrophages,
      granulocytes or other infiltrates, and a rich extracellular matrix. The choroid
      plexus is mainly involved in the production of cerebrospinal fluid (CSF) by using
      the free access to the blood compartment of the leaky vessels. In order to
      separate blood and CSF compartments, choroid plexus epithelial cells and
      tanycytes of circumventricular organs constitute the blood-CSF-brain barrier. As
      non-neuronal cells in the brain and derived from neuroectoderm, choroid plexus
      epithelia are defined as a subtype of macroglia. The choroid plexus is involved
      in a variety of neurological disorders, including neurodegenerative,
      inflammatory, infectious, traumatic, neoplastic, and systemic diseases. Abeta and
      Biondi ring tangles accumulate in the Alzheimer's disease choroid plexus. In
      multiple sclerosis, the choroid plexus could represent a site for lymphocyte
      entry in the CSF and brain, and for presentation of antigens. Recent studies have
      provided new diagnostic markers and potential molecular targets for choroid
      plexus papilloma and carcinoma, which represent the most common brain tumors in
      the first year of life. We here revive some of the classical studies and review
      recent insight into the biology and pathology of the choroid plexus.

PMID- 20033191
TI  - Apolipoprotein E4 and psoriasis.

PMID- 20033192
TI  - Imiquimod induces apoptosis of human melanocytes.
AB  - Development of vitiligo-like hypopigmentary lesions associated with topical
      imiquimod has been reported. We hypothesized that mode of action of imiquimod in
      melanocytes may include triggering of apoptosis resulted in loss of cells, which
      may be a possible mechanism of imiquimod-induced hypopigmentary lesions.
      Therefore, we investigated whether imiquimod induces apoptosis of human
      melanocytes and also whether it modulates expression of apoptosis-related
      molecules in human melanocytes. Imiquimod treatment induced apoptosis of
      melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining.
      Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane
      potential in melanocytes. The apoptotic activity of imiquimod was associated with
      caspase-3, Bcl-2 and mitogen-activated protein kinase expression in melanocytes.
      These results indicated that imiquimod induces apoptosis of melanocytes. These
      findings may provide a clue to understand pathogenesis of imiquimod-induced
      vitiligo-like hypopigmentary lesions.

PMID- 20033193
TI  - Protease and pro-inflammatory cytokine concentrations are elevated in chronic
      compared to acute wounds and can be modulated by collagen type I in vitro.
AB  - Physiological wound repair is a highly regulated, complex process, which leads to
      formation of new tissue after injury. However, the healing process is not perfect
      and healing impairments can occur. Delayed healing and formation of chronic
      wounds has been linked to the excessive production of proteolytic enzymes leading
      to reduced amounts of growth factors and successive destruction of the
      extracellular matrix. It has been implied that there is an alteration in the
      normal control mechanisms regulating the levels of these enzymes. The study
      presented provides data on the concentration of proteases and cytokines in wound
      fluid from chronic when compared with acute wounds. Levels of proteases such as
      PMN elastase, matrix metalloproteinases-2 (MMP-2), and MMP-13 were found to be
      profoundly elevated in chronic when compared with acute wound fluids. In
      addition, concentrations of IL-1beta, IL-6, and IL-8 were shown to be
      significantly higher in chronic than in acute wounds. Furthermore, the ability of
      a wound dressing, consisting of bovine collagen type I, to bind pro-inflammatory
      cytokines was investigated. Collagen type I was able to bind significant amounts
      of the pro-inflammatory cytokines in vitro. Thus, it should be able to establish
      a more physiological wound milieu in vivo and promote healing.

PMID- 20033194
TI  - Gastroesophageal reflux/laryngopharyngeal reflux disease:  a critical analysis of
      the literature.
AB  - Despite the wealth of publications on the topic of gastroesophageal reflux and
      its variants, there are still many unsettled questions before one accepts the
      prevalent cult of "reflux disease". This study is summarizing the results of the
      critical analysis of the literature, 436 articles,during the last 30 years. The
      golden test to identify the patient group suffering from this rather common
      phenomenon is still lacking. The claimed extra-esophageal manifestations
      especially in the larynx are non-specific and may be caused by other factors well
      known within the domain of vocology. The response to therapeutic intervention
      still lacks serious well-controlled studies to allow drawing reasonable
      conclusions. An outstanding feature of the publications is that most of them fall
      in the category of "review". It seems that there is a tendency to perpetuate the
      concept without objective criticism. Following the analysis, a recommendation for
      anew plan of original well-controlled multi-center studies is highlighted.

PMID- 20033195
TI  - Treatment of velopharyngeal insufficiency by autologous fat injection.
AB  - Velopharyngeal insufficiency (VPI) is a structural or functional trouble, which
      causes hypernasal speech. Velopharyngeal flaps, speech therapy and augmentation
      pharyngoplasty, using different implants, have all been used to address this
      trouble. We hereby present our results following rhinopharyngeal autologous fat
      injection in 18 patients with mild velopharyngeal insufficiency (12 soft palate
      clefts, 4 functional VPI, 2 myopathy). 28 injections were carried out between
      2004 and 2007. The degree of hypernasal speech was evaluated pre- and
      postoperatively by a speech therapist and an ENT specialist and quantified by an
      acoustic nasometry (Kay Elemetrics). All patients were exhaustively treated with
      preoperative speech therapy (average, 8 years). The mean value of the nasalance
      score was 37% preoperatively and 23% postoperatively (p = 0.015). The
      hypernasality was reduced postoperatively in all patients (1-3 degrees of the
      Borel-Maisonny score). There were no major complications, two minor complications
      (one hematoma, one cervical pain). The autologous fat injection is a simple,
      safe, minimally invasive procedure. It proves to be efficient in cases of mild
      velopharyngeal insufficiency or after a suboptimal velopharyngoplasty.

PMID- 20033196
TI  - Does hypercapnia ameliorate hyperoxia-induced lung injury in neonatal rats?
AB  - Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown
      to improve pulmonary function in certain models of lung injury. We tested the
      null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats.
      The prospective, randomized study was set at Research laboratory in Children's
      Hospital. Forty-five newborn rats were randomly assigned to three groups (n =
      15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) >
      0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry
      weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL
      1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using
      a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and
      hemorrhage was significantly increased from a median value of 1.5 in normoxia to
      2.5 in hyperoxia (P < 0.05) and 3.0 with TH (P < 0.001, nonparametric ANOVA). The
      interstitial space relative to the alveolar space, as a measure of
      hypercellularity, was increased by 18% during hyperoxia and by 44% with TH
      compared with normoxia. TH significantly increased the size of the interstitial
      space by 22% compared with hyperoxia (P < 0.001). The lung wet-weight to dry
      weight ratio was increased by 10% in both hyperoxic groups (P < 0.001). Both
      hyperoxic groups showed significant reductions in the concentration of IL-1beta
      compared with normoxia (P < 0.001), whereas the ratio of IL-1beta to IL-10 was
      significantly decreased, indicating an anti-inflammatory trend. TH does not
      prevent histological manifestations of hyperoxic lung injury in spontaneously
      breathing neonatal rats and may worsen the outcome.

PMID- 20033197
TI  - SUV39h-independent association of HP1 beta with fibrillarin-positive nucleolar
      regions.
AB  - Heterochromatin protein 1 (HP1), which binds to sites of histone H3 lysine 9
      (H3K9) methylation, is primarily responsible for gene silencing and the formation
      of heterochromatin. We observed that HP1 beta is located in both the
      chromocenters and fibrillarin-positive nucleoli interiors. However, HP1 alpha and
      HP1 gamma occupied fibrillarin-positive compartments to a lesser extent,
      corresponding to the distinct levels of HP1 subtypes at the promoter of rDNA
      genes. Deficiency of histone methyltransferases SUV39h and/or inhibition of
      histone deacetylases (HDACi) decreased HP1 beta and H3K9 trimethylation at
      chromocenters, but not in fibrillarin-positive regions that co-localized with RNA
      polymerase I. Similarly, SUV39h- and HDACi-dependent nucleolar rearrangement and
      inhibition of rDNA transcription did not affect the association between HP1 beta
      and fibrillarin. Moreover, the presence of HP1 beta in nucleoli is likely
      connected with transcription of ribosomal genes and with the role of fibrillarin
      in nucleolar processes.

PMID- 20033199
TI  - Haplotype block: a new type of forensic DNA markers.
AB  - Forensic DNA analysis is currently performed using highly discriminating short
      tandem repeat (STR) markers. SNPs are being investigated as adjunct tools for
      human identity testing because of their abundance in the human genome, utility
      for genotyping degraded DNA samples, and amenability to automation. While SNPs
      can provide an alternative approach, on a per locus basis they have a lower power
      of discrimination (PD) than STRs. With the discovery of block structures in the
      human genome, a novel set of SNP markers are available for further exploration of
      forensic utility. Several neighboring, tightly linked SNPs are inherited together
      and form a haplotype block, which as a haploblock has a higher discrimination
      power than the individual SNPs within the block. Candidate haplotype blocks were
      selected from three major populations (Caucasian, East Asian, and African) using
      the following parameters: maximum match probability reduction = 0.85, linkage
      disequilibrium (LD) r(2) >= 0.7, maximum F(st) = 0.06, minimum number of SNPs =
      3, minimum heterozygosity = 0.2, and minimum number of haplotypes = 3. From the
      HapMap Phase II data, 253 haploblocks were identified on the 22 autosomal
      chromosomes. After removing haploblocks deviating from the Hardy-Weinberg
      equilibrium (HWE) or in LD with other haploblocks, 24 haploblocks remained as
      candidates for forensic consideration. The cumulative PD of these blocks can
      reach 10(-12) in the populations studied. The data support within and between
      haplotype independence even when they are syntenic. We propose guidelines for
      evidence interpretation that address the application of haplotype blocks for
      transfer evidence, mixture, and kinship analyses.

PMID- 20033198
TI  - Chromatin insulators specifically associate with different levels of higher-order
      chromatin organization in Drosophila.
AB  - Chromatin insulators are required for proper temporal and spatial expression of
      genes in metazoans. Here, we have analyzed the distribution of insulator proteins
      on the 56F-58A region of chromosome 2R in Drosophila polytene chromosomes to
      assess the role of chromatin insulators in shaping genome architecture. Data show
      that the suppressor of Hairy-wing protein [Su(Hw)] is found in three structures
      differentially associated with insulator proteins: bands, interbands, and multi
      gene domains of coexpressed genes. Results show that bands are generally formed
      by condensation of chromatin that belongs to genes containing one or more Su(Hw)
      binding sites, whereas, in interbands, Su(Hw) sites appear associated with open
      chromatin. In addition, clusters of coexpressed genes in this region form bands
      characterized by the lack of CP190 and BEAF-32 insulator proteins. This pattern
      correlates with the distribution of specific chromatin marks and is conserved in
      nurse cells, suggesting that this organization may not be limited to one cell
      type but represents the basic organization of interphasic chromosomes.

PMID- 20033200
TI  - Neurocognitive dysfunction in adult moyamoya disease.
AB  - We wanted to determine the neurocognitive profile of adult patients with moyamoya
      disease prior to neurosurgical intervention. The experience of three United
      States medical centers, Columbia University, University of Illinois at Chicago,
      and the University of Texas Southwestern Medical Center at Dallas, were combined.
      Clinical data from adult patients (N = 29) referred for neuropsychological
      evaluation from 1996 to 2008 were reviewed. Neurocognitive functioning was
      assessed using standardized neuropsychological tests and all data were converted
      to z-scores. Memory, attention, processing speed, verbal memory, visuo-spatial,
      language, and executive functions were examined. Cognitive dysfunction was
      defined as performance in two or more cognitive domains 1.5 standard deviations
      below age-corrected normative means OR one or more cognitive domains two standard
      deviations below age-corrected normative means. Manual strength and dexterity, as
      well as depressive symptoms, were also assessed. Two-thirds of patients
      demonstrated neurocognitive dysfunction. A large proportion of patients were
      found to have pronounced cognitive dysfunction (>2 SD below the mean) on tests of
      processing speed (29%), verbal memory (31%), verbal fluency (26%) and executive
      function (25%). Manual strength and dexterity were also affected in many
      patients, with impairment found in 36-58% of patients. Twenty-eight percent of
      patients reported moderate to severe depression, but depressive symptoms did not
      correlate with neurocognitive findings. A large proportion of adults with
      moyamoya disease demonstrate disruption of neurocognition in a broad range of
      functions, particularly those mediated by subcortical and frontal regions. The
      pattern of deficits suggests a mechanism of diffuse small vessel disease possibly
      caused by chronic hypoperfusion.

PMID- 20033201
TI  - Arachnoiditis and communicating hydrocephalus as a complication of epidural blood
      patch.

PMID- 20033202
TI  - Microembolic signals in systemic lupus erythematosus and other cerebral small
      vessel diseases.
AB  - Microembolic signals (MES) are detected by transcranial Doppler (TCD), and are
      mainly observed in cardiac and large-artery diseases; however they might also be
      observed in conditions affecting small vessels of the brain. We aimed to review
      the current medical literature related to MES assessed by TCD in patients with
      cerebral small vessel disease. We conducted a systematic review in PubMed and
      selected the articles with information on this topic. Systemic lupus
      erythematosus (SLE) is the disease with more articles; pooled data showed a
      frequency of MES of 14.9%. MES were more frequent in SLE patients with
      antiphospholipid antibodies and ischemic stroke. MES have also been described in
      other diseases such as primary antiphospholipid syndrome, Sneddon's syndrome, and
      Behcet's disease. Further studies assessing the significance of MES in the
      pathogenesis of neurological manifestations of these disorders is warranted.

PMID- 20033203
TI  - Skin microvascular reactivity in trained adolescents.
AB  - Whilst endothelial dysfunction is associated with a sedentary lifestyle, enhanced
      endothelial function has been documented in the skin of trained individuals. The
      purpose of this study was to investigate whether highly trained adolescent males
      possess enhanced skin microvascular endothelial function compared to their
      untrained peers. Seventeen highly and predominantly soccer trained boys
      (V(O)(2)(peak): 55 +/- 6 mL kg(-1) min(-1)) and nine age- and maturation-matched
      untrained controls (V(O)(2)(peak): 43 +/- 5 mL kg(-1) min(-1)) aged 13-15 years
      had skin microvascular endothelial function assessed using laser Doppler
      flowmetry. Baseline and maximal thermally stimulated skin blood flow (SkBF)
      responses were higher in forearms of trained subjects compared to untrained
      participants [baseline SkBF: 11 +/- 4 vs. 9 +/- 3 perfusion units (PU), p < 0.05;
      SkBF(max): 282 +/- 120 vs. 204 +/- 68 PU, p < 0.05]. Similarly, cutaneous
      vascular conductance (CVC) during local heating was superior in the forearm skin
      of trained versus untrained individuals (CVC(max): 3 +/- 1 vs. 2 +/- 1 PU mmHg(
      1), p < 0.05). Peak hyperaemia following arterial occlusion and area under the
      reactive hyperaemia curve were also greater in forearm skin of the trained group
      (peak hyperaemia: 51 +/- 21 vs. 35 +/- 15 PU, p < 0.05; area under curve: 1596 +/
      739 vs. 962 +/- 796 PUs, p < 0.05). These results suggest that chronic exercise
      training in adolescents is associated with enhanced microvascular endothelial
      vasodilation in non-glabrous skin.

PMID- 20033204
TI  - Effects of ammonium chloride ingestion on phosphocreatine metabolism during
      moderate- and heavy-intensity plantar-flexion exercise.
AB  - This study examined the effects of NH(4)Cl ingestion on phosphocreatine (PCr)
      metabolism during 9 min of moderate- (MOD) and heavy- (HVY) intensity constant
      load isotonic plantar-flexion exercise. Healthy young adult male subjects (n = 8)
      completed both a control (CON) and NH(4)Cl ingestion (ACID) trial. Phosphorus-31
      magnetic resonance spectroscopy was used to monitor changes in intracellular pH
      (pHi), [Pi], [PCr], and [ATP]. During the Middle (3-6 min) and Late (6-9 min)
      stages of HVY, ACID was associated with a higher (P < 0.05) intracellular
      hydrogen-ion concentration ([H(+)]i) [Middle: 246 (SD 36) vs. 202 (SD 36)
      mmol/l]; [Late: 236 (SD 35) vs. 200 (SD 39) mmol/l]. In addition, ACID was
      associated with a lower (P < 0.05) [PCr] relative to CON during the Early (0-3
      min) [18.1 (SD 5.1) vs. 20.4 (SD 5.4) mmol/l] and Middle stages [14.1 (SD 5.4)
      vs. 16.7 (SD 6.0) mmol/l] of HVY. The amplitude of the primary component of PCr
      breakdown during the transition to HVY was greater in ACID than CON [14.5 (SD 5.8
      vs. 11.3 (SD 4.8) mmol/l], however, the PCr slow component (continued slow
      decline in [PCr]) showed no difference (P > 0.05). The time constant for PCr
      breakdown (tauPCr) was greater in HVY than MOD for both conditions [58 (SD 22)
      vs. 28 (SD 15) s ACID; 51 (SD 20) vs. 29 (SD 14) s CON] (P < 0.05). In summary,
      ACID increased PCr breakdown during the transition from MOD to HVY, but did not
      increase the magnitude of the PCr slow component.

PMID- 20033205
TI  - Use of continuous glucose monitoring in normoglycemic, insulin-resistant women.
AB  - The purpose of this study was to compare fasting and post-prandial glucose
      concentrations measured in venous blood with continuous glucose monitoring (CGM)
      derived values, with and without prior exercise, in insulin-resistant,
      normoglycemic women. Interstitial and venous glucose concentrations were assessed
      in ten sedentary, overweight/obese African-American women following a sedentary
      condition (75 min of rest) and following an exercise condition (75 min of brisk
      walking on a treadmill). Ninety minutes after rest or exercise, participants
      completed an oral glucose tolerance test (OGTT). In response to the OGTT, CGM
      derived glucose area under the curves (AUC) were lower than venous values in the
      exercise condition (-25%, p = 0.03) but this difference was attenuated in the
      sedentary condition (-10%, p = 0.09). Additionally, CGM-derived absolute glucose
      values (mMol) were significantly lower compared to venous values during the
      sedentary (p = 0.007) and exercise conditions (p = 0.006). Overall, there was a
      moderately strong relationship between venous and CGM-derived glucose AUC (r (2)
      = 0.68) but the CGM-derived values were consistently lower in this study group.
      Although CGM provided more information regarding post-prandial glucose responses,
      these results suggest that CGM may not closely match venous glucose measurements
      in normoglycemic participants.

PMID- 20033206
TI  - Influence of training status and exercise modality on pulmonary O(2) uptake
      kinetics in pre-pubertal girls.
AB  - The limited available evidence suggests that endurance training does not
      influence the pulmonary oxygen uptake (V(O)(2)) kinetics of pre-pubertal
      children. We hypothesised that, in young trained swimmers, training status
      related adaptations in the V(O)(2) and heart rate (HR) kinetics would be more
      evident during upper body (arm cranking) than during leg cycling exercise. Eight
      swim-trained (T; 11.4 +/- 0.7 years) and eight untrained (UT; 11.5 +/- 0.6 years)
      girls completed repeated bouts of constant work rate cycling and upper body
      exercise at 40% of the difference between the gas exchange threshold and peak
      V(O)(2). The phase II V(O)(2) time constant was significantly shorter in the
      trained girls during upper body exercise (T: 25 +/- 3 vs. UT: 37 +/- 6 s; P <
      0.01), but no training status effect was evident in the cycle response (T: 25 +/-
      5 vs. UT: 25 +/- 7 s). The V(O)(2) slow component amplitude was not affected by
      training status or exercise modality. The time constant of the HR response was
      significantly faster in trained girls during both cycle (T: 31 +/- 11 vs. UT: 47
      +/- 9 s; P < 0.01) and upper body (T: 33 +/- 8 vs. UT: 43 +/- 4 s; P < 0.01)
      exercise. The time constants of the phase II V(O)(2)and HR response were not
      correlated regardless of training status or exercise modality. This study
      demonstrates for the first time that swim-training status influences upper body
      V(O)(2) kinetics in pre-pubertal children, but that cycle ergometry responses are
      insensitive to such differences.

PMID- 20033207
TI  - Monitoring endurance running performance using cardiac parasympathetic function.
AB  - The aims of the present study were to (1) assess relationships between running
      performance and parasympathetic function both at rest and following exercise, and
      (2) examine changes in heart rate (HR)-derived indices throughout an 8-week
      period training program in runners. In 14 moderately trained runners (36 +/- 7
      years), resting vagal-related HR variability (HRV) indices were measured daily,
      while exercise HR and post-exercise HR recovery (HRR) and HRV indices were
      measured fortnightly. Maximal aerobic speed (MAS) and 10 km running performance
      were assessed before and after the training intervention. Correlations (r > 0.60,
      P < 0.01) were observed between changes in vagal-related indices and changes in
      MAS and 10 km running time. Exercise HR decreased progressively during the
      training period (P < 0.01). In the 11 subjects who lowered their 10 km running
      time >0.5% (responders), resting vagal-related indices showed a progressively
      increasing trend (time effect P = 0.03) and qualitative indications of possibly
      and likely higher values during week 7 [+7% (90% CI -3.7;17.0)] and week 9 [+10%
      (90% CI -1.5;23)] compared with pre-training values, respectively. Post-exercise
      HRV showed similar changes, despite less pronounced between-group differences.
      HRR showed a relatively early possible decrease at week 3 [-20% (90% CI -42;10)],
      with only slight reductions near the end of the program. The results illustrate
      the potential of resting, exercise and post-exercise HR measurements for both
      assessing and predicting the impact of aerobic training on endurance running
      performance.

PMID- 20033208
TI  - A comparative study of pattern synchronization detection between neural signals
      using different cross-entropy measures.
AB  - Cross-approximate entropy (X-ApEn) and cross-sample entropy (X-SampEn) have been
      employed as bivariate pattern synchronization measures for characterizing
      interdependencies between neural signals. In this study, we proposed a new
      measure, cross-fuzzy entropy (X-FuzzyEn), to describe the synchronicity of
      patterns. The performances of three statistics were first quantitatively tested
      using five different coupled systems including both deterministic and stochastic
      models, i.e., coupled broadband noises, Lorenz-Lorenz, Rossler-Rossler, Rossler
      Lorenz, and neural mass model. All the measures were compared with each other
      with respect to their ability to distinguish between different levels of coupling
      and their robustness against noise. The three measures were then applied to a
      real-life problem, pattern synchronization analysis of left and right hemisphere
      rat electroencephalographic (EEG) signals. Both simulated and real EEG data
      analysis results showed that the X-FuzzyEn provided an improved evaluation of
      bivariate series pattern synchronization and could be more conveniently and
      powerfully applied to different neural dynamical systems contaminated by noise.

PMID- 20033209
TI  - The let-7a microRNA protects from growth of lung carcinoma by suppression of k
      Ras and c-Myc in nude mice.
AB  - PURPOSE: Down-regulation of let-7 microRNA (miRNA) plays an important role in the
      pathogenesis of lung cancer. k-Ras and c-Myc, two key oncogenes in lung cancer,
      have been found to be targeted by let-7 in vitro. However, the in vivo relevance
      of these findings is unknown. The aim of the present study is to determine the
      effect of let-7a, a member of let-7 family, on the growth of lung cancer in vivo
      and to investigate whether let-7-induced suppression of k-Ras and c-Myc is
      involved in lung cancer. METHODS: A549-let-7a cell line and A549-control cell
      line, two stable transfected cell lines over-expressing let-7a and the control
      miRNA, were established and preserved in our lab. A549, A549-control, and A549
      let-7a cells were injected subcutaneously into nude mice, respectively. After 30
      days, the mice were killed; the xenografts were excised and weighed. The
      expression of let-7a in tumor xenografts was assessed by real-time reverse
      transcription-PCR (RT-PCR). The expression of k-Ras and c-Myc in xenografts were
      determined by western blot and immunohistochemistry detection. RESULTS: Real-time
      RT-PCR showed the expression of let-7a was increased significantly in A549-let-7a
      cells-injected group, compared with A549-control cells-injected group and A549
      cells-injected group (P < 0.01). In the xenografts of A549-let-7a cells-injected
      group, a significant depression in tumor weight (P < 0.05) and significant
      decrease of k-Ras and c-Myc protein were observed (P < 0.01), compared to A549
      cells-injected group and A549-control cells-injected group. CONCLUSION:
      Overexpression of let-7a can inhibit the growth of lung cancer transplanted
      subcutaneously in nude mice by suppression of k-Ras and c-Myc.

PMID- 20033210
TI  - A chromosome study and localization of 18S rDNA in Khawia saurogobii (Cestoda:
      Caryophyllidea).
AB  - This paper reports results of the first cytogenetic study carried out on a
      recently described monozoic tapeworm, Khawia saurogobii Xi et al., 2009, from the
      Chinese lizard gudgeon (Saurogobio dabryi). The karyotype of this species is
      composed of eight pairs of metacentric and telocentric chromosomes (2n = 16; n =
      3m + 5t), metacentric chromosomes representing the first, sixth, and eight pairs.
      All chromosomes except the largest pair displayed 4',6-diamidino-2-phenylidole
      (DAPI) positive heterochromatin in centromeric regions. In mitotic preparations
      stained with Giemsa, one of the homologues of a smaller metacentric chromosome
      pair (No. 7) showed a distinct secondary constriction, whereas the other did not.
      Fluorescent in situ hybridization (FISH) with 18S ribosomal DNA (rDNA) probe
      revealed that the chromosomes No. 7 carry each a cluster of ribosomal genes
      associated with the centromeric heterochromatin and confirmed that this
      chromosome pair contains a nucleolar organizer region (NOR). The rDNA-FISH also
      confirmed heteromorphism in the size of NOR (i.e., secondary constriction)
      observed after Giemsa staining. The present cytogenetic analysis revealed species
      specific characters of K. saurogobii and showed that FISH may represent a new
      valuable cytogenetic tool suitable for comparative taxonomic or phylogenetic
      studies within the order Caryophyllidea in the future.

PMID- 20033211
TI  - Sarcocystis calchasi sp. nov. of the domestic pigeon (Columba livia f. domestica)
      and the Northern goshawk (Accipiter gentilis): light and electron microscopical
      characteristics.
AB  - A novel highly pathogenic Sarcocystis species has been shown to cycle between the
      Northern goshawk (Accipiter gentilis) as definitive host and the domestic pigeon
      (Columba livia f. domestica) as intermediate host. However, genetically based
      characteristics are only available from very few bird-infecting Sarcocystis
      species. We therefore further characterised morphological properties of this
      protozoan in both hosts. Using light and electron microscopy, oocysts and
      sporocysts as well as schizonts and sarcocysts were characterised and compared
      with available morphological features of previously reported Sarcocystis species
      of Northern goshawks, Columbidae and genetically closely related species of other
      avian hosts. Sporocysts shed from day 6 on after experimental infection by the
      Northern goshawk were of ovoid appearance (11.9 x 7.9 microm). Ultrastructurally,
      schizonts of all developmental stages were found in the liver, spleen and next to
      or in endothelial cells of various organs of domestic pigeons 7 to 12 days after
      experimental infection. The cyst wall surface of slender sarcocysts (1 to 2 mm in
      length and 20 to 50 microm in width) was smooth and lacked protrusions.
      Cystozoites were lancet-shaped and measured 7.5 x 1.5 microm in Giemsa stain
      smears. The morphological findings, when combined with data of experimental
      infection and genetic studies, convergently indicate that the recently discovered
      Sarcocystis species represents a new species. We therefore propose to name this
      parasite Sarcocystis calchasi species nova.

PMID- 20033212
TI  - Large intron 14 rearrangement in APC results in splice defect and attenuated FAP.
AB  - Familial adenomatous polyposis [FAP (OMIM 175100)] is an autosomal dominant
      colorectal cancer predisposition syndrome characterized by hundreds to thousands
      of colonic polyps and, if untreated by a combination of screening and/or surgical
      intervention, an approximately 99% lifetime risk of colorectal cancer. A subset
      of FAP patients develop an attenuated form of the condition characterized by
      lower numbers of colonic polyps (highly variable, but generally less than 100)
      and a lower lifetime risk of colorectal cancer, on the order of 70%. We report
      the diagnosis of three attenuated FAP families due to a 1.4-kb deletion within
      intron 14 of APC, originally reported clinically as a variant of unknown
      significance (VUS). Sequence analysis suggests that this arose through an Alu
      mediated recombination event with a locus on chromosome 6q22.1. This mutation is
      inherited by family members who presented with an attenuated FAP phenotype, with
      variable age of onset and severity. Sequence analysis of mRNA revealed an
      increase in the level of aberrant splicing of exon 14, resulting in the
      generation of an exon 13-exon 15 splice-form that is predicted to lead to a
      frameshift and protein truncation at codon 673. The relatively mild phenotypic
      presentation and the intra-familial variation are consistent with the leaky
      nature of exon 14 splicing in normal APC. The inferred founder of these three
      families may account for as yet undetected affected branches of this kindred.
      This and similar types of intronic mutations may account for a significant
      proportion of FAP cases where APC clinical analysis fails because of the current
      limitations of testing options.

PMID- 20033213
TI  - Dynamics of extracellular matrix in ovarian follicles and corpora lutea of mice.
AB  - Despite the mouse being an important laboratory species, little is known about
      changes in its extracellular matrix (ECM) during follicle and corpora lutea
      formation and regression. Follicle development was induced in mice (29 days of
      age/experimental day 0) by injections of pregnant mare's serum gonadotrophin on
      days 0 and 1 and ovulation was induced by injection of human chorionic
      gonadotrophin on day 2. Ovaries were collected for immunohistochemistry (n=10 per
      group) on days 0, 2 and 5. Another group was mated and ovaries were examined on
      day 11 (n=7). Collagen type IV alpha1 and alpha2, laminin alpha1, beta1 and
      gamma1 chains, nidogens 1 and 2 and perlecan were present in the follicular basal
      lamina of all developmental stages. Collagen type XVIII was only found in basal
      lamina of primordial, primary and some preantral follicles, whereas laminin
      alpha2 was only detected in some preantral and antral follicles. The focimatrix,
      a specialised matrix of the membrana granulosa, contained collagen type IV alpha1
      and alpha2, laminin alpha1, beta1 and gamma1 chains, nidogens 1 and 2, perlecan
      and collagen type XVIII. In the corpora lutea, staining was restricted to
      capillary sub-endothelial basal laminas containing collagen type IV alpha1 and
      alpha2, laminin alpha1, beta1 and gamma1 chains, nidogens 1 and 2, perlecan and
      collagen type XVIII. Laminins alpha4 and alpha5 were not immunolocalised to any
      structure in the mouse ovary. The ECM composition of the mouse ovary has
      similarities to, but also major differences from, other species with respect to
      nidogens 1 and 2 and perlecan.

PMID- 20033214
TI  - Cost of co-infection controlled by infectious dose combinations and food
      availability.
AB  - To what extent the combined effect of several parasite species co-infecting the
      same host (i.e. polyparasitism) affects the host's fitness is a crucial question
      of ecological parasitology. We investigated whether the ecological setting can
      influence the co-infection's outcome with the mosquito Aedes aegypti and two
      parasites: the microsporidium Vavraia culicis and the gregarine Ascogregarina
      culicis. The cost of being infected by the two parasites depended on the
      interaction between the two infectious doses and host food availability. The age
      at pupation of the mosquito was delayed most when the doses of the two parasites
      were highest and little food was available. As infectious dose increases with the
      parasites' prevalence and intensity of transmission, the cost of being co
      infected depends on the epidemiological status of the two parasite species.

PMID- 20033215
TI  - Natural habitat change, commercial fishing, climate, and dispersal interact to
      restructure an Alaskan fish metacommunity.
AB  - The metacommunity concept has recently been described to account for the roles of
      dispersal in regulating community structure. Despite its strong theoretical
      basis, there exist few large-scale and long-term examples of its applicability in
      aquatic ecosystems. In this study we used a long-term dataset (1961-2007) on the
      relative abundances of the dominant limnetic fishes from two interconnected lakes
      to investigate the synergistic effects of naturally declining lake volume
      (approximately 50% in 50 years), climate variation, fishery management, and
      dispersal on community composition. We found a marked shift in fish community
      composition and variability during a period of rapid natural habitat change;
      however, the change was most apparent in the downstream, more stable lake of the
      system rather than at the site of disturbance. Multivariate analysis suggested
      significant shifts in community composition and variability in the downstream
      lake. Results indicated that the community composition in both lakes was best
      explained by habitat loss in the upper watershed and the number of spawning adult
      sockeye salmon the previous year (reflecting both natural processes and
      commercial fishing). Furthermore, communities exhibited site-specific responses
      to climatic conditions (e.g., index of the Pacific Decadal Oscillation), whereby
      the upper lake responded to climate within a given year and with a 1-year time
      lag, whereas the downstream community responded only with a 1-year lag. We
      attribute this difference largely to downstream dispersal and recruitment of fish
      from the upper lake. Thus, we suggest that the interconnected nature of the
      communities in this system provides a useful and large-scale example of the
      metacommunity concept, whereby the effects of environmental disturbance on
      community structure ultimately depend on the effects of these disturbances on
      dispersal among ecosystems.

PMID- 20033216
TI  - Invasive rats alter woody seedling composition on seabird-dominated islands in
      New Zealand.
AB  - Invasive rats (Rattus rattus, R. norvegicus, R. exulans) have large impacts on
      island habitats through both direct and indirect effects on plants. Rats affect
      vegetation by extirpating burrowing seabirds through consumption of eggs, chicks,
      and adults. These seabirds serve as ecosystem engineers, affecting plant
      communities by burying and trampling seeds and seedlings, and by altering
      microclimate. Rats also directly affect plant communities by consuming seeds and
      seedlings. We studied the direct and indirect impacts of rats on the seedlings of
      woody plants on 21 islands in northern New Zealand. We compared seedling
      densities and richness on islands which differed in status with respect to rats:
      nine islands where rats never invaded, seven islands where rats were present at
      the time of our study, and five islands where rats were either eradicated or
      where populations were likely to be small as a result of repeated eradications
      and re-invasions. In addition, we compared plots from a subset of the 21 islands
      with different burrow densities to examine the effects of burrowing seabirds on
      plants while controlling for other factors that differ between islands. We
      categorized plant communities by species composition and seedling density in a
      cluster analysis. We found that burrow densities explained more variation in
      seedling communities than rat status. In areas with high seabird burrow density
      seedling densities were low, especially for the smallest seedlings. Species
      richness and diversity of seedlings, but not seedling density, were most
      influenced by changes in microclimate induced by seabirds. Islands where rats had
      been eradicated or that had low rat populations had the lowest diversity and
      richness of seedlings (and adults), but the highest seedling density. Seedling
      communities on these islands were dominated by Pseudopanax lessonii and Coprosma
      macrocarpa. This indicates lasting effects of rats that may prevent islands from
      returning to pre-invasion states.

PMID- 20033217
TI  - Phosphorus-mediated changes in life history traits of the invasive New Zealand
      mudsnail (Potamopyrgus antipodarum).
AB  - Understanding the mechanisms that species use to succeed in new environments is
      vital to predicting the extent of invasive species impacts. Food quality is
      potentially important because it can affect population dynamics by affecting life
      history traits. The New Zealand mudsnail, Potamopyrgus antipodarum, is a
      worldwide invader. We examined how mudsnail growth rate and fecundity responded
      to the C:P ratio of algal food in laboratory conditions. Mudsnails fed low-P
      algae (C:P 1,119) grew more slowly, matured later, produced smaller offspring,
      and grew to a smaller adult size than snails reared on algae with high levels of
      P. A relatively small increase in algal C:P (203-270) significantly increased
      mudsnail age at maturity. We suggest that the relatively high body P requirements
      of mudsnails make them susceptible to allocation trade-offs between growth and
      reproduction under P-limited conditions. The elemental composition of algae
      varies greatly in nature, and over half of the rock biofilms in streams surveyed
      within the introduced range of mudsnails in the Greater Yellowstone Area had C:P
      ratios above which could potentially pose P limitation of life history traits.
      High growth rate and fecundity are common traits of many species that become
      invasive and are also associated with high-P demands. Therefore, fast-growing
      consumers with high P demands, such as mudsnails, are potentially more sensitive
      to P limitation suggesting that limitation of growth and reproduction by food
      quality is an important factor in understanding the resource demands of invasive
      species.

PMID- 20033218
TI  - Laparoscopic splenectomy in portal hypertension: a single-surgeon 13-year
      experience.
AB  - BACKGROUND: Although laparoscopic splenectomy (LS) has become the standard
      approach for most splenectomy cases, some areas still remain controversial. To
      date, the indications that preclude LS are not clearly defined. Portal
      hypertension from liver cirrhosis still is a contraindication to LS in the
      clinical practice guidelines of the European Association for Endoscopic Surgery
      published in 2008. This study aimed to evaluate the feasibility of LS for
      hypersplenism secondary to liver cirrhosis and portal hypertension. METHODS: The
      study retrospectively analyzed 206 laparoscopic splenectomies performed for a
      variety of indications over 13 years. According to diagnosis, the patients were
      divided into group A (hypersplenism secondary to liver cirrhosis and portal
      hypertension, n = 96) and group B (hematologic and other disorders, n = 110). A
      detailed review of medical records was conducted. The perioperative data for the
      two groups were compared including patient characteristics, diagnosis, operative
      details, complication rates, and postoperative hospital stay. RESULTS:
      Laparoscopic splenectomy was completed for 201 patients. Conversion from
      laparoscopic to open surgery was necessary for 5 patients (2.4%) because of
      hemorrhage, and 26 patients (12.6%) had complications. There were significant
      differences between groups A and B in terms of mean operation time (2.8 vs. 2.1
      h), complication rates (17.7% vs. 8.2%), and postoperative stay (7.1 vs. 4.7
      days). However, the two groups showed no significant differences with respect to
      intraoperative blood loss, blood transfusion, and conversion rate. CONCLUSION:
      Laparoscopic splenectomy is a feasible, effective, and safe surgical procedure
      for patients who require splenectomy. Hypersplenism secondary to cirrhosis and
      portal hypertension should not be considered contraindications for LS.

PMID- 20033219
TI  - Successful treatment of collapsing focal segmental glomerulosclerosis with a
      combination of rituximab, steroids and ciclosporin.
AB  - We report a case of a 2-year-old boy with steroid- and ciclosporin (CsA)
      resistant collapsing focal segmental glomerulosclerosis (FSGS) who went into
      complete remission with a combination of IV rituximab and methylprednisolone
      pulse therapy (MPT) while receiving oral CsA. He was initially treated with
      steroids including MPT, CsA, and plasmapheresis, but his massive proteinuria and
      severe systemic edema persisted. We treated him with four weekly doses of
      intravenous rituximab. After the second administration of rituximab, his
      proteinuria and systemic edema were dramatically improved, but hypoalbuminemia
      and proteinuria persisted. Eight months after the onset, he was re-treated with
      two courses of MPT. Thereafter, he finally went into complete remission 1 month
      after MPT. He continued in remission for 8 months with CsA, but then relapsed.
      However, he went into complete remission again with 60 mg/m(2) of oral
      prednisolone without rituximab and since then, he has been in remission with CsA.
      This is the first report of the successful treatment of collapsing FSGS with
      rituximab. Thus, rituximab emerges as a new therapeutic option against refractory
      collapsing FSGS.

PMID- 20033220
TI  - Fetal growth restriction, catch-up growth and the early origins of insulin
      resistance and visceral obesity.
AB  - There is an association between growing slowly before birth, accelerated growth
      in early postnatal life and the emergence of insulin resistance, visceral obesity
      and glucose intolerance in adult life. In this review we consider the pathway
      through which intrauterine growth restriction (IUGR) leads to the initial
      increase in insulin sensitivity and to catch-up growth. We also discuss the
      importance of the early insulin environment in determining later visceral
      adiposity and the intrahepatic mechanisms that may result in the emergence of
      glucose intolerance in a subset of IUGR infants. We present evidence that a key
      fetal adaptation to poor fetal nutrition is an upregulation of the abundance of
      the insulin receptor in the absence of an upregulation of insulin signalling in
      fetal skeletal muscle. After birth, however, there is an upregulation in the
      abundance of the insulin receptor and the insulin signalling pathway in the IUGR
      offspring. Thus, the origins of the accelerated postnatal growth rate experienced
      by IUGR infants lie in the fetal adaptations to a poor nutrient supply. We also
      discuss how the intracellular availability of free fatty acids and glucose within
      the visceral adipocyte and hepatocyte in fetal and neonatal life are critical in
      determining the subsequent metabolic phenotype of the IUGR offspring. It is clear
      that a better understanding of the relative contributions of the fetal and
      neonatal nutrient environment to the regulation of key insulin signalling
      pathways in muscle, visceral adipose tissue and the liver is required to support
      the development of evidence-based intervention strategies and better outcomes for
      the IUGR infant.

PMID- 20033222
TI  - Idiopathic membranous nephropathy associated with polycystic kidney disease.
AB  - Membranous nephropathy (MN) and polycystic kidney disease are both relatively
      rare diseases in children. On rare exceptions, these two conditions have been
      associated in adults. We report here the first case of a pediatric patient with
      this association. This 6-year-old child presented with gross hematuria, nephrotic
      syndrome, and mild renal failure. A renal ultrasound subsequently revealed that
      the patient also had polycystic kidney disease.

PMID- 20033221
TI  - The IGF/IGFBP system in relation to macroscopic bone architecture in pediatric
      renal transplant patients.
AB  - The post-transplant bone disease of the peripheral skeleton in pediatric renal
      transplant recipients is characterized by an inadequately thin bone cortex in
      relation to muscular force. A major hormonal modulator of periosteal growth is
      the insulin-like growth factor (IGF)/IGF binding protein (IGFBP) system. We
      therefore hypothesized that the reduced cortical thickness in these patients may
      be due to functional IGF deficiency. To test this hypothesis, we investigated 55
      patients (mean estimated glomerular filtration rate 86.3 +/- 30.0 ml/min/1.73
      m(2)) in a cross-sectional study. Parameters of macroscopic bone architecture and
      forearm muscle size were analyzed by peripheral quantitative computed tomography
      (pQCT), and serum IGF/IGFBP system components were measured by specific
      radioimmunoassays. The mean (+/- standard deviation) standardized serum IGF-I
      (0.20 +/- 1.16 score) level was normal, while the mean IGF-II (1.16 +/- 0.11
      score) level was significantly elevated. Serum IGFBP-1 and IGFBP-2 levels were
      not altered, whereas the IGFBP-3 (1.34 +/- 0.15 score) level was significantly
      increased. The serum IGFBP-4 level was slightly elevated (by 11%), the IGFBP-6
      level was markedly (2.3-fold) elevated, while the IGFBP-5 level was comparable to
      that of the control. The respective age-adjusted cortical thickness at both the
      proximal (r = 0.407, P < 0.005) and distal (r = 0.383, P < 0.01) forearm was
      positively correlated with the standardized serum IGF-I level. In conclusion, the
      serum IGF/IGFBP system in pediatric renal transplant recipients is characterized
      by an increase in the levels of the inhibitory IGFBPs, IGFBP-3, -4 and -6,
      resulting in a functional IGF deficiency. The positive correlation of IGF-I with
      cortical thickness underlines the importance of this hormonal system in the
      modeling of bone, particularly periosteal growth.

PMID- 20033223
TI  - Hypokalemic rhabdomyolysis in congenital tubular disorders: a case series and a
      systematic review.
AB  - Hypokalemia is a recognized cause of rhabdomyolysis but very few reports document
      its association with inborn renal tubular disorders. We report our experience
      with hypokalemic rhabdomyolysis in 5 pediatric patients affected by inborn renal
      tubular disorders and the results of a careful review of the literature
      disclosing 9 further cases for a total of 14 patients (8 male and 6 female
      subjects, aged between 1.6 and 46, median 16 years). The inborn renal tubular
      disorders underlying rhabdomyolysis were classic distal renal tubular acidosis (n
      = 7), Gitelman syndrome (n = 5), classic Bartter syndrome (n = 1), and antenatal
      Bartter syndrome (n = 1). In 8 patients rhabdomyolysis followed an acute
      intestinal disease, an upper respiratory illness or the discontinuation of
      regular medication. Five patients experienced two or more episodes of
      rhabdomyolysis. In 10 patients the underlying renal tubular disorder was
      recognized concurrently with the episode of rhabdomyolysis or some weeks later.
      In conclusion some congenital renal tubular disorders predispose to hypokalemic
      rhabdomyolysis. Prevention of discontinuation of regular medication and
      electrolyte repair in the context of acute intercurrent illnesses might avoid the
      development of hypokalemic rhabdomyolysis.

PMID- 20033224
TI  - Clinical course of children requiring prolonged continuous renal replacement
      therapy.
AB  - A prospective observational study was performed to analyze the clinical course of
      critically ill children who require continuous renal replacement therapy (CRRT).
      Variables associated with prolonged CRRT were analyzed. Of the 174 children
      treated with CRRT, 32 (18.3%) required CRRT for >14 days and 20 (11.5%) for >21
      days. Prolonged CRRT was more common in patients with heart disease and those
      requiring mechanical ventilation, hemodiafiltration, and higher doses of heparin.
      The same factors were found when patients with CRRT for >14 days and 21 days were
      studied. Overall mortality rate was 35.6%; it was slightly higher in patients on
      prolonged CRRT (43.7% with CRRT > 14 days and 45% with CRRT >21 days), though the
      differences were not statistically significant. We conclude that there were no
      differences in the pre-CRRT clinical characteristics, severity of illness, and
      renal function in critically ill children requiring prolonged CRRT. Prolonged
      CRRT was more frequently required by patients with heart disease and those on
      mechanical ventilation. Patients with prolonged CRRT required more frequent
      hemodiafiltration and higher doses of heparin. Mortality was slightly higher in
      children with longer CRRT, though this difference did not reach statistical
      significance.

PMID- 20033225
TI  - Rituximab in refractory nephrotic syndrome.
AB  - The aim of this study was to establish the efficacy and safety of rituximab in
      refractory nephrotic syndrome (NS). Members of the International Paediatric
      Nephrology Association were asked to retrospectively fill in a questionnaire with
      details on the use of rituximab in their centres. We divided the data into three
      groups: group 1, patients with steroid-dependent and frequently relapsing NS;
      group 2, with steroid-resistant NS; group 3, with post-transplant recurrence of
      NS. Seventy questionnaires from 25 centres described the outcome of 28, 27 and 15
      patients in groups 1, 2 and 3, respectively. Of these, 82% of patients in group
      1, 44% of patients in group 2 and 60% of patients in group 3 had a good initial
      response. Side effects were observed in 27% of the patients, and these were
      mostly acute reactions. We present a large multicentre series of children with
      refractory NS. Children in group 1 showed the best response. The good initial
      response in group 3 can be biased by the accompanying treatments that were
      administered at the same time as rituximab. Controlled prospective trials are
      required to establish the value of rituximab in idiopathic NS.

PMID- 20033226
TI  - Determination of sexual organ development.
AB  - Plant sexual organ development is initiated from the floral meristem. At early
      stages, the activation of a set of genes that encode transcription factors
      determines the identity of the floral organs. These transcription factors are
      known as organ identity genes, and they form multimeric complexes that bind to
      target genes to control their expression. The transcriptional regulation of
      target genes triggers the formation of an organ by activating pathways required
      for its development initiating a cascade of events that leads to sexual plant
      reproduction. Here, I review the complex mechanisms involved in transcriptional
      regulation of organ identity genes and how they determine sexual organ
      development. Their expression is the result of complex interactions between
      repressors and activators that are often coexpressed. After the production of
      floral identity proteins, the formation of multimeric complexes defines target
      specificity and exerts a transcriptional regulatory effect on the target. Thanks
      to an increasing knowledge of the molecular control of sexual organ development
      in multiple species, we are beginning to understand how these genes evolved and
      how reproductive organ development occurs in different groups of plants.
      Comparative studies will, in future, provide a new insight into mechanisms of
      sexual organ development.

PMID- 20033227
TI  - Cost comparison of gastrojejunostomy versus duodenal stent placement for
      malignant gastric outlet obstruction.
AB  - BACKGROUND: Gastrojejunostomy (GJJ) and stent placement are the most commonly
      used palliative treatments for malignant gastric outlet obstruction (GOO). In a
      recent randomized trial, stent placement was preferred in patients with a
      relatively short survival and GJJ in patients with a longer survival. As health
      economic aspects have only been studied in general terms, we estimated the cost
      of GJJ and that of stent placement in such patients. METHODS: In the SUSTENT
      study, patients were randomized to GJJ (n = 18) or stent placement (n = 21).
      Pancreatic cancer was the most common cause of GOO. We compared initial costs and
      costs during follow-up. For cost-effectiveness, the incremental cost
      effectiveness ratio was calculated. RESULTS: Food intake improved more rapidly
      after stent placement than after GJJ, but long-term relief of obstructive
      symptoms was better after GJJ. More major complications (P = 0.02) occurred and
      more reinterventions were performed (P < 0.01) after stent placement than after
      GJJ. Initial costs were higher for GJJ compared to stent placement (euro8315 vs.
      euro4820, P < 0.001). We found no difference in follow-up costs. Total costs per
      patient were higher for GJJ compared to stent placement (euro12433 vs. euro8819,
      P = 0.049). The incremental cost-effectiveness ratio of GJJ compared to stent
      placement was euro164 per extra day with a gastric outlet obstruction scoring
      system (GOOSS) >or=2 adjusted for survival. CONCLUSIONS: Medical effects were
      better after GJJ, although GJJ had higher total costs. Since the cost difference
      between the two treatments was only small, cost should not play a predominant
      role when deciding on the type of treatment assigned to patients with malignant
      GOO (ISRCTN 06702358).

PMID- 20033228
TI  - A glycine-rich protein that facilitates exine formation during tomato pollen
      development.
AB  - Formation of the unique and highly diverse outer cell wall, or exine, of pollen
      is essential for normal pollen function and survival. However, little is known
      about the many contributing proteins and processes involved in the formation of
      this wall. The tomato gene LeGRP92 encodes for a glycine-rich protein produced
      specifically in the tapetum. LeGRP92 is found as four major forms that accumulate
      differentially in protein extracts from stamens at different developmental
      stages. The three largest molecular weight forms accumulated during early
      microspore development, while the smallest molecular weight form of LeGRP92 was
      present in protein extracts from stamens from early microsporogenesis through
      anther dehiscence, and was the only form present in dehisced pollen. Light
      microscopy immunolocalization experiments detected LeGRP92 at only two stages,
      late tetrad and early free microspore. However, we observed accumulation of the
      LeGRP92 at the early tetrad stage of development by removing the callose wall
      from tetrads, which allowed LeGRP92 detection. Transmission electron microscopy
      confirmed the LeGRP92 accumulation from microspore mother cells, tetrads through
      anther dehiscence. It was observed in the callose surrounding the microspore
      mother cells and tetrads, the exine of microspores and mature pollen, and
      orbicules. Plants expressing antisense RNA had reduced levels of LeGRP92 mRNA and
      protein, which correlated to pollen with altered exine formation and reduced
      pollen viability and germination. These data suggest that the LeGRP92 has a role
      in facilitating sporopollenin deposition and uniform exine formation and pollen
      viability.

PMID- 20033229
TI  - The MADS-domain protein MPF1 of Physalis floridana controls plant architecture,
      seed development and flowering time.
AB  - Floral and vegetative development of plants is dependent on the combinatorial
      action of MADS-domain transcription factors. Members of the STMADS11 subclade,
      such as MPF1 of Physalis, are abundantly expressed in leaves as well as in floral
      organs, but their function is not yet clear. Our studies with transgenic
      Arabidopsis that over-express MPF1 suggest that MPF1 interacts with SOC1 to
      determine flowering time. However, MPF1 RNAi-mediated knockdown Physalis plants
      revealed a complex phenotype with changes in flowering time, plant architecture
      and seed size. Flowering of these plants was delayed by about 20% as compared to
      wild type. Expression of PFLFY is upregulated in the MPF1 RNAi lines, while PFFT
      and MPF3 genes are strongly repressed. MPF1 interacts with a subset of MADS
      domain factors, namely with PFSOC1 in planta, and with PFSEP3 and PFFUL in yeast,
      supporting a regulatory role for this protein in flowering. The average size of
      seeds produced by the transgenic MPF1 RNAi plants is increased almost twofold.
      The height of these plants is also increased about twofold, but most axillary
      buds are stunted when compared to controls. Taken together, this suggests that
      members of the STMADS11 subclade act as positive regulators of flowering but have
      diverse functions in plant growth.

PMID- 20033230
TI  - The speed of mitochondrial movement is regulated by the cytoskeleton and myosin
      in Picea wilsonii pollen tubes.
AB  - Strategic control of mitochondrial movements and cellular distribution is
      essential for correct cell function and survival. However, despite being a vital
      process, mitochondrial movement in plant cells is a poorly documented phenomenon.
      To investigate the roles of actin filaments and microtubules on mitochondrial
      movements, Picea wilsonii pollen tubes were treated with two microtubule
      disrupting drugs, two actin-disrupting drugs and a myosin inhibitor. Following
      these treatments, mitochondrial movements were characterized by multiangle
      evanescent wave microscopy and laser-scanning confocal microscopy. The results
      showed that individual mitochondria underwent three classes of linear movement:
      high-speed movement (instantaneous velocities >5.0 microm/s), low-speed movement
      (instantaneous velocities <5.0 microm/s) and variable-speed movement
      (instantaneous velocities ranging from 0.16 to 10.35 microm/s). 10 nM latrunculin
      B induced fragmentation of actin filaments and completely inhibited mitochondrial
      vectorial movement. Jasplakinolide treatment induced a 28% reduction in
      chondriome motility, and dramatically inhibition of high-speed and variable-speed
      movements. Treatment with 2,3-butanedione 2-monoxime caused a 61% reduction of
      chondriome motility, and the complete inhibition of high-speed and low-speed
      movements. In contrast to actin-disrupting drugs, microtubule-disrupting drugs
      caused mild effects on mitochondrial movement. Taxol increased the speed of
      mitochondrial movement in cortical cytoplasm. Oryzalin induced curved
      mitochondrial trajectories with similar velocities as in the control pollen
      tubes. These results suggest that mitochondrial movement at low speeds in pollen
      tubes is driven by myosin, while high-speed and variable-speed movements are
      powered both by actin filament dynamics and myosin. In addition, microtubule
      dynamics has profound effects on mitochondrial velocity, trajectory and
      positioning via its role in directing the arrangement of actin filaments.

PMID- 20033231
TI  - Response of wild-type and high pigment-1 tomato fruit to UV-B depletion:
      flavonoid profiling and gene expression.
AB  - The tomato high pigment-1 (hp-1) mutant is characterised by exaggerated
      photoresponsiveness and increased fruit pigmentation, and carries a mutation in
      the HP1/LeDDB1 gene, encoding the tomato homologue of the negative regulator of
      the light signal transduction DDB1a from Arabidopsis. Here, we investigated the
      molecular events underlying flavonoid accumulation in flesh and peel of wild-type
      and hp-1 fruits in presence or absence of UV-B light. In hp-1 peel, a twofold
      higher level of rutin and an earlier accumulation of flavonoids than in wild-type
      were observed, which correlated to the earlier activation of most flavonoid
      biosynthetic genes compared to wild-type. In hp-1 flesh, flavonoid content was up
      to 8.5-fold higher than in wild-type and correlated to the higher transcript
      level of flavonoid genes compared to wild-type. In both tissues, the expression
      of flavonoid genes was correlated with the anticipated and/or enhanced activation
      of the light signal transduction genes: LeCOP1LIKE, LeCOP1 and LeHY5. In wild
      type, flavonoid content was severely reduced by UV-B depletion mostly in peel,
      whereas in hp-1 it was significantly increased in flesh. The activation of
      flavonoid and light signal transduction genes was UV-B dependent mostly at the
      mature green stage, whereas LeDDB1 expression was not regulated by UV-B.

PMID- 20033232
TI  - Renal cell carcinoma with mixed features of papillary and clear cell
      cytomorphology: a fluorescent in situ hybridization study.
AB  - We performed fluorescent in situ hybridization (FISH) to investigate the numeric
      change of chromosomes 7, 17, and Y and loss of chromosome 3p in "papillary renal
      cell carcinomas (RCC) with extensive clear cell changes (CCC)." Consecutive cases
      of RCC over a 12-year period were reviewed to identify "papillary RCC with
      extensive CCC." Immunostaining for cytokeratin 7 and alpha-methylacyl-CoA
      racemase (AMACR) and FISH for chromosomes 7, 17, Y, and 3p were applied. Of the
      total of 521 RCC retrieved, there were 49 RCC with papillary architecture and
      clear cell areas that could be divided into: Group 1 (12 cases), typical clear
      cell RCC with focal areas of papillary formation; Group 2 (28 cases), focal
      typical papillary RCC having papillary architecture with extensive CCC; and Group
      3 (nine cases), RCC with an admixture of eosinophilic/clear cytoplasm and
      solid/papillary architecture. Group 1 showed negative immunoreactivity for CK7
      and AMACR and absence of numeric chromosomal gain or loss of chromosomes 7/17 and
      Y. Groups 2 and 3 showed variable reactivity for CK7 and AMACR. Tumors in group 2
      and five in group 3 showed trisomies of chromosomes 7 and/or 17 with or without
      loss of chromosome Y. Loss of small arm 3p was observed in groups 1 and 3 but not
      in group 2 tumors. In conclusion, papillary RCC may show phenotypical CCC
      mimicking clear cell RCC. In a small number of cases with mixed histopathological
      features, FISH is helpful in subtyping RCC.

PMID- 20033233
TI  - Increasing hematocrit above 28% during early resuscitative phase is not
      associated with decreased mortality following severe traumatic brain injury.
AB  - BACKGROUND: To prevent iatrogenic damage, transfusions of red blood cells should
      be avoided. For this, specific and reliable transfusion triggers must be defined.
      To date, the optimal hematocrit during the initial operating room (OR) phase is
      still unclear in patients with severe traumatic brain injury (TBI). We
      hypothesized that hematocrit values exceeding 28%, the local hematocrit target
      reached by the end of the initial OR phase, resulted in more complications,
      increased mortality, and impaired recovery compared to patients in whom
      hematocrit levels did not exceed 28%. METHODS: Impact of hematocrit (independent
      variable) reached by the end of the OR phase on mortality and morbidity
      determined by the extended Glasgow outcome scale (eGOS; dependent variables) was
      investigated retrospectively in 139 TBI patients. In addition, multiple logistic
      regression analysis was performed to identify additional important variables.
      FINDINGS: Following severe TBI, mortality and morbidity were neither aggravated
      by hematocrit above 28% reached by the end of the OR phase nor worsened by the
      required transfusions. Upon multiple logistic regression analysis, eGOS was
      significantly influenced by the highest intracranial pressure and the lowest
      cerebral perfusion pressure values during the initial OR phase. CONCLUSIONS:
      Based on this retrospective observational analysis, increasing hematocrit above
      28% during the initial OR phase following severe TBI was not associated with
      improved or worsened outcome. This questions the need for aggressive transfusion
      management. Prospective analysis is required to determine the lowest acceptable
      hematocrit value during the OR phase which neither increases mortality nor
      impairs recovery. For this, a larger caseload and early monitoring of cerebral
      metabolism and oxygenation are indispensable.

PMID- 20033234
TI  - Knee MR arthrographic proof of an articular origin for combined intraneural and
      adventitial cysts.

PMID- 20033236
TI  - Tic disorders and the premonitory urge.
AB  - The aims of this study were to examine a non-English (Hebrew) version of a scale
      that measures the premonitory urge in children suffering from tic disorder, as
      well as examine the correlations of the urge with demographic and clinical
      aspects of Tourette Syndrome. Forty children and adolescents, suffering from tics
      participated in this study. They were assessed with the Premonitory Urge for Tics
      Scale (PUTS); the Yale Global Tic Severity Scale (YGTSS); the Childhood Version
      of the Yale Brown Obsessive Compulsive Scale (CYBOCS); the ADHD Rating Scale IV
      (Conners) Scale; the Screen for Child Anxiety Related Emotional Disorders
      (SCARED); and the Child Depression Inventory (CDI). The mean PUTS score was 20.15
      (SD = 5.89). For the entire sample the PUTS was found to be internally consistent
      at a = 0.79. Youths older than 10 years had higher consistency (a = 0.83) than
      youths younger than 10 (a = 0.69). Premonitory urge was not correlated with tic
      severity in the entire sample. In youths older than 10, as opposed to youths
      younger than 10, premonitory urge did correlate with obsessions, compulsions and
      depression, but not with anxiety or with ADHD. The premonitory urge can be
      measured reliably and the PUTS is a useful instrument for measuring this
      important phenomena. Premonitory urges seems to be related to obsessions,
      compulsions, and depression in older children and this may have implications for
      the developmental psychopatholgy of these symptoms.

PMID- 20033235
TI  - 1 Hz rTMS preconditioned by tDCS over the primary motor cortex in Parkinson's
      disease: effects on bradykinesia of arm and hand.
AB  - To investigate whether a period of 1 Hz repetitive transcranial magnetic
      stimulation (rTMS) over M1 preconditioned by tDCS improves bradykinesia of the
      upper limb in Parkinson's disease (PD). Fifteen patients with PD performed index
      finger, hand tapping and horizontal pointing movements as well as reach-to-grasp
      movements with either hand before (baseline conditions) and after a period of 1
      Hz rTMS preconditioned by (1) sham, (2) anodal or (3) cathodal tDCS over the
      primary motor cortex contralateral to the more affected body side. Movement
      kinematics was analysed using an ultrasound-based motion analyser at baseline,
      immediately after and 30 min after each stimulation session. Dopaminergic
      medication was continued. Compared to baseline, 1 Hz rTMS significantly increased
      the frequency of index finger and hand tapping as well as horizontal pointing
      movements performed with the contralateral hand. Movement frequency increased up
      to 40% over 30 min after cessation of the stimulation. Preconditioning with
      cathodal tDCS, but not with anodal tDCS, reduced the effectiveness of 1 Hz rTMS
      to improve tapping and pointing movements. There was no significant increase of
      movement frequencies of the ipsilateral hand induced by 1 Hz rTMS preconditioned
      by either tDCS session. Movement kinematics of reach-to-grasp movements were not
      significantly influenced by either stimulation session. In PD the beneficial
      effects of 1 Hz rTMS over the primary motor cortex on bradykinesia of simple
      finger, hand and pointing movements is reduced by preconditioning with cathodal
      tDCS, but not with anodal tDCS. Preconditioning with tDCS is a powerful tool to
      modulate the behavioural effect of 1 Hz rTMS over the primary motor cortex in PD.

PMID- 20033237
TI  - Taurine restores Axl/Gas6 expression in vascular smooth muscle cell calcification
      model.
AB  - Our previous studies demonstrated that taurine inhibits osteoblastic
      differentiation of vascular smooth muscular cells (VSMCs) via the mitogen
      activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)
      signaling pathway, but the underlying mechanism is not elucidated. The tyrosine
      kinase receptor Axl and its ligand growth arrest-specific protein 6 (Gas6) are
      expressed in VSMCs. Axl/Gas6 signaling system is known to inhibit VSMCs
      calcification. We herein showed that taurine partially restored Axl and Gas6
      expression in beta-glycerophosphate (beta-GP)-induced VSMC calcification model.
      Taurine also induced activation of ERK, but not other two MAPKs including c-jun N
      terminal Kinase (JNK) and p38 in VSMCs. Either knockdown of the taurine
      transporter (TAUT) or treatment with the ERK-specific inhibitor PD98059 blocked
      the activation of ERK by taurine and abolished taurine-induced Axl/Gas6
      expression and calcium deposition reduction in beta-GP-induced VSMC calcification
      model. These results demonstrate for the first time that taurine stimulates
      expression of Axl and Gas6 via TAUT/ERK signaling pathway in beta-GP-induced VSMC
      calcification model.

PMID- 20033238
TI  - Thermodynamics of binding of regulatory ligands to tissue transglutaminase.
AB  - The transamidating activity of tissue transglutaminase is regulated by the
      ligands calcium and GTP, via conformational changes which facilitate or interfere
      with interaction with the peptidyl-glutamine substrate. We have analysed binding
      of these ligands by calorimetric and computational approaches. In the case of GTP
      we have detected a single high affinity site (K (D) approximately 1 microM), with
      moderate thermal effects suggestive that binding GTP involves replacement of GDP,
      normally bound to the protein. On line with this possibility no significant
      binding was observed during titration with GDP and computational studies support
      this view. Titration with calcium at a high cation molar excess yielded a complex
      binding isotherm with a number of "apparent binding sites" in large excess over
      those detectable by equilibrium dialysis (6 sites). This binding pattern is
      ascribed to occurrence of additional thermal contributions, beyond those of
      binding, due to the occurrence of conformational changes and to catalysis itself
      (with protein self-crosslinking). In contrast only one site for binding calcium
      with high affinity (K (D) approximately 0.15 microM) is observed with samples of
      enzyme inactivated by alkylation at the active site (to prevent enzyme
      crosslinkage and thermal effects of catalysis). These results indicate an
      intrinsic ability of tissue transglutaminase to bind calcium with high affinity
      and the necessity of careful reassessment of the enzyme regulatory pattern in
      relation to the concentrations of ligands in living cells, taking also in account
      effects of ligands on protein subcellular compartimentation.

PMID- 20033239
TI  - How does long-term parenteral nutrition impact the bone mineral status of
      children with intestinal failure?
AB  - Patients on long-term parenteral nutrition (PN) are at significantly increased
      risk for the development of metabolic bone disease (MBD); this condition is
      characterized by incomplete mineralization of osteoid with consequent
      disturbances ranging from osteopenia to severe bone disease with fractures. The
      aim of the study was: (1) to evaluate the prevalence of MBD, (2) to identify the
      PN- or intestinal failure (IF)-related factors and (3) to assess annual changes
      of bone mineral status. Since September 2005 all patients affected by IF and
      treated with PN started a BMD evaluation program using dual-energy X-ray
      absorptiometry (DXA). Twenty-four IF patients were included [15 with short bowel
      syndrome (SBS), 5 with severe protracted diarrhea and 4 with chronic intestinal
      pseudostruction]. The bone mineral density (BMD) Z-score was significantly lower
      in patients than in the control group. In our series SBS patients showed a BMD Z
      score significantly higher in comparison with the medical causes of IF. No
      significant correlations were found between bone mineral status and PN duration
      and nutrient intake. Nine IF patients were submitted to a second DXA evaluation
      after 1 year from the baseline. All bone mineral variables were significantly
      increased at the second DXA evaluation. The high prevalence of MBD in IF patients
      undergoing long-term treatment with PN requires that these patients undergo
      careful and periodic monitoring of their bone mineral status; patients with
      congenital gut dysfunctions, such as epithelium defects and motility anomalies,
      are at major risk of developing this complication, probably due to the
      association with extra-intestinal causes of bone loss.

PMID- 20033242
TI  - Depression and anxiety in children and adolescents with familial Mediterranean
      fever.
AB  - Familial Mediterranean fever (FMF) is the most common autoinflammatory disease
      which requires a lifelong treatment. The aim of this study was to evaluate the
      depression and anxiety in pediatric FMF patients. The Children's Depression
      Inventory and the Screen for Child Anxiety-related Emotional Disorders were the
      instruments used. Forty-three patients with FMF and 53 healthy controls were
      compared. Both study and control groups were divided into two age groups, 7-12
      and 13-18 years. The depression scores of patients with FMF were significantly
      higher than their healthy peers (p = 0.001). However, there was no significant
      difference between patients with FMF and control group regarding the anxiety
      scores (p = 0.78). The disease duration was not significantly correlated with
      depression and anxiety scores. There was a significant correlation between
      depression score and FMF severity score (p = 0.01). The mean depression and
      anxiety scores of the FMF patients were positively correlated with the number of
      attacks (p = 0.000 and p = 0.001, respectively).This study suggested that
      patients with FMF were considerably more depressed than their healthy peers and
      that the depression scores were negatively affected from disease severity score
      and number of attacks. Psychosocial assessment of children with FMF has potential
      clinical implications and individualized counseling and interventions are needed.

PMID- 20033243
TI  - Henoch-Schonlein purpura in childhood: treatment and prognosis. Analysis of 425
      cases over a 5-year period.
AB  - The objective of this study was to identify the most effective treatment by
      evaluating the different therapies used to treat mild, moderate, and severe
      Henoch-Schonlein purpura (HSP) patients. We performed a retrospective study of
      children discharged with a diagnosis of HSP. The study group consisted of 425
      children divided into mild, moderate, and severe condition groups. Different
      therapeutic protocols of hydrocortisone sodium succinate (HCSS) therapy,
      methylprednisolone (MP) pulse therapy, and MP combination with tripterygium
      glycoside (TG) therapy were used to treat the different groups. The evaluation of
      curative effect was performed. After 4 weeks, all patients with no obvious
      recovery were treated by strengthening the different treatment intervention. The
      remission time of skin, joint, and gastrointestinal manifestations was evaluated,
      and the results of the follow-up were analyzed (remission time of proteinuria,
      relapse, and side effects of therapy). After 4 weeks, in the mild group, the
      difference of the curative effect between HCSS and MP therapy was not
      statistically significant. Moderate HSP patients were more likely to respond to
      MP therapy than HCSS therapy (P < 0.05). Severe HSP patients were more likely to
      respond to MP combination with TG than single MP therapy (P < 0.05). At last
      follow-up, they all had normal urinalysis. In the moderate HSP group, the mean
      duration of proteinuria was shorter in the MP pulse therapy group than in the
      HCSS therapy group (P < 0.05). In the mild group, the mean duration of purpura
      was shorter in HCSS therapy group than in the MP pulse therapy group (P < 0.05).
      At last follow-up, 99 patients had recurrences of purpura and/or proteinuria and
      41 patients had liver functional impairment and/or hypertension. The relapse and
      side effects were all satisfactorily controlled, and the rates of relapse and
      side effects did not differ between groups with different therapies (P > 0.05).
      Our study has demonstrated a superior effect for HCSS therapy in patients with
      mild HSP disease, for MP therapy in patients with moderate disease, and for MP
      combined with TG therapy in patients with severe disease. MP therapy administered
      initially reduces the duration of urinary protein abnormality. The therapeutic
      protocols did not increase the risk of relapse and were safe.

PMID- 20033240
TI  - Eating disorders: the current status of molecular genetic research.
AB  - Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders
      characterized by disordered eating behavior where the patient's attitude towards
      weight and shape, as well as their perception of body shape, are disturbed.
      Formal genetic studies on twins and families suggested a substantial genetic
      influence for AN and BN. Candidate gene studies have initially focused on the
      serotonergic and other central neurotransmitter systems and on genes involved in
      body weight regulation. Hardly any of the positive findings achieved in these
      studies were unequivocally confirmed or substantiated in meta-analyses. This
      might be due to too small sample sizes and thus low power and/or the genes
      underlying eating disorders have not yet been analyzed. However, some studies
      that also used subphenotypes (e.g., restricting type of AN) led to more specific
      results; however, confirmation is as yet mostly lacking. Systematic genome-wide
      linkage scans based on families with at least two individuals with an eating
      disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4
      (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region
      led to the (as yet unconfirmed) identification of certain variants associated
      with AN. Genome-wide association studies are under way and will presumably help
      to identify genes and pathways involved in these eating disorders. The
      elucidation of the molecular mechanisms underlying eating disorders might improve
      therapeutic approaches.

PMID- 20033244
TI  - Patient preference and acceptability of calcium plus vitamin D3 supplementation:
      a randomised, open, cross-over trial.
AB  - Preference for a drug formulation is important in adherence to long-term
      medication for chronic illnesses such as osteoporosis. We investigated the
      preference for and acceptability of chewable tablet containing calcium and
      vitamin D (Calci Chew D(3), Nycomed) compared to that of a sachet containing
      calcium and vitamin D(3) (Cad, Will-Pharma). This open, randomised, cross-over
      trial was set up to compare the preference and acceptability of two calcium plus
      vitamin D(3) formulations (both with 500 mg calcium and 400/440 IU vitamin D3),
      given twice a day in patients with osteoporosis. Preference and acceptability
      were assessed by means of questionnaires. Preference was determined by asking the
      question, which treatment the patient preferred, and acceptability was measured
      by scoring five variables, using rating scales. Of the 102 patients indicating a
      preference for a trial medication, 67% preferred the chewable tablet, 19% the
      sachet with calcium and vitamin D(3,) and 15% stated no preference. The
      significant preference for Calci Chew D(3) (p < 0.0001) was associated with
      higher scores for all five acceptability variables. The two formulations were
      tolerated equally well. A significant greater number of patients considered the
      chewable tablet as preferable and acceptable to the sachet, containing calcium
      and vitamin D(3). TRIAL REGISTRATION: Current Controlled Trials ISRCTN18822358.

PMID- 20033245
TI  - Laparoscopic colectomy for transverse colon carcinoma.
AB  - BACKGROUND: Laparoscopic resection of transverse colon carcinoma is technically
      demanding and was excluded from most of the large trials of laparoscopic
      colectomy. The aim of this study was to assess the safety, feasibility, and
      outcome of laparoscopic resection of carcinoma of the transverse colon. METHODS:
      A retrospective review was performed to identify patients who underwent
      laparoscopic resection of transverse colon carcinoma. These patients were
      compared to patients who had laparoscopic resection for right and sigmoid colon
      carcinoma. In addition, they were compared to a historical series of patients who
      underwent open resection for transverse colon cancer. RESULTS: A total of 22
      patients underwent laparoscopic resection for transverse colon carcinoma. Sixty
      eight patients operated for right colon cancer and 64 operated for sigmoid colon
      cancer served as comparison groups. Twenty-four patients were identified for the
      historical open group. Intraoperative complications occurred in 4.5% of patients
      with transverse colon cancer compared to 5.9% (P = 1.0) and 7.8% (P = 1.0) of
      patients with right and sigmoid colon cancer, respectively. The early
      postoperative complication rate was 45, 50 (P = 1.0), and 37.5% (P = 0.22) in the
      three groups, respectively. Conversion was required in 1 (5%) patient in the
      laparoscopic transverse colon group. The conversion rate and late complications
      were not significantly different in the three groups. There was no significant
      difference in the number of lymph nodes harvested in the laparoscopic and open
      groups. Operative time was significantly longer in the laparoscopic transverse
      colectomy group when compared to all other groups (P = 0.001, 0.008, and <0.001
      compared to right, sigmoid, and open transverse colectomy, respectively).
      CONCLUSIONS: The results of laparoscopic colon resection for transverse colon
      carcinoma are comparable to the results of laparoscopic resection of right or
      sigmoid colon cancer and open resection of transverse colon carcinoma. These
      results suggest that laparoscopic resection of transverse colon carcinoma is safe
      and feasible.

PMID- 20033246
TI  - Electrically evoked auditory steady state responses in cochlear implant users.
AB  - Auditory steady state responses are neural potentials in response to repeated
      auditory stimuli. This study shows that electrically evoked auditory steady state
      responses (EASSRs) to low-rate pulse trains can be reliably recorded by
      electrodes placed on the scalp of a cochlear implant (CI) user and separated from
      the artifacts generated by the electrical stimulation. Response properties are
      described, and the predictive value of EASSRs for behaviorally hearing thresholds
      is analyzed. For six users of a Cochlear Nucleus CI, EASSRs to symmetric biphasic
      pulse trains with rates between 35 and 47 Hz were recorded with seven scalp
      electrodes. The influence of various stimulus parameters was assessed: pulse
      rate, stimulus intensity, monopolar or bipolar stimulation mode, and presentation
      of either one pulse train on one electrode or interleaved pulse trains with
      different pulse rates on multiple electrodes. To compensate for the electrical
      artifacts caused by the stimulus pulses and radio frequency transmission,
      different methods of artifact reduction were employed. The validity of the
      recorded responses was confirmed by recording on-off responses, determination of
      response latency across the measured pulse rates, and comparison of amplitude
      growth of stimulus artifact and response amplitude. For stimulation in the 40 Hz
      range, response latencies of 35.6 ms (SD = 5.3 ms) were obtained. Responses to
      multiple simultaneous stimuli on different electrodes can be evoked, and the
      electrophysiological thresholds determined from EASSR amplitude growth in the 40
      Hz range correlate well with behaviorally determined threshold levels for pulse
      rates of 41 Hz.

PMID- 20033247
TI  - Context effects in the discriminability of spatial cues.
AB  - In order to investigate whether performance in an auditory spatial discrimination
      task depends on the prevailing listening conditions, we tested the ability of
      human listeners to discriminate target sounds with and without presentation of a
      preceding sound. Target sounds were either lateralized by means of interaural
      time differences (ITDs) of +400, 0, or -400 micros or interaural level
      differences (ILDs) with the same subjective intracranial locations. The preceding
      sound was always lateralized by means of ITD. This allowed for testing whether
      the effects of a preceding sound were location- or cue-specific. Preceding sounds
      and target sounds were randomly paired across trials. Listeners had to
      discriminate whether they perceived the target sounds as coming from the same or
      different intracranial locations. Finally, stimuli were selected so that, without
      any preceding sound, ITD and ILD cues were equally discriminable at all target
      lateralizations. Stimuli were 800 Hz-wide, 400-ms duration bands of noise
      centered at 500 Hz, presented over headphones. The duration of the preceding
      sound was randomly selected from a uniform distribution spanning from 1s to 2s.
      Results show that discriminability of both binaural cues was improved for midline
      target positions when preceding sound and targets were co-located, whereas it was
      impaired when preceding sound and targets came from different positions. No
      effect of the preceding sound was found for left or right target positions. These
      results are compatible with a purely bottom-up mechanism based on adaptive coding
      of ITD around the midline that may be combined with top-down mechanisms to
      increase localization accuracy in realistic listening conditions.

PMID- 20033249
TI  - Google rocks.

PMID- 20033248
TI  - The dependence of auditory nerve rate adaptation on electric stimulus parameters,
      electrode position, and fiber diameter: a computer model study.
AB  - This paper describes results from a stochastic computational neuron model that
      simulates the effects of rate adaptation on the responses to electrical
      stimulation in the form of pulse trains. We recently reported results from a
      single-node computational model that included a novel element that tracks
      external potassium ion concentration so as to modify membrane voltage and cause
      adaptation-like responses. Here, we report on an improved version of the model
      that incorporates the anatomical components of a complete feline auditory nerve
      fiber (ANF) so that conduction velocity and effects of manipulating the site of
      excitation can be evaluated. Model results demonstrate rate adaptation and
      changes in spike amplitude similar to those reported for feline ANFs. Changing
      the site of excitation from a central to a peripheral axonal site resulted in
      plausible changes in latency and relative spread (i.e., dynamic range). Also,
      increasing the distance between a modeled ANF and a stimulus electrode tended to
      decrease the degree of rate adaptation observed in pulse-train responses. This
      effect was clearly observed for high-rate (5,000 pulse/s) trains but not low-rate
      (250 pulse/s) trains. Finally, for relatively short electrode-to-ANF distances,
      increases in modeled ANF diameter increased the degree of rate adaptation. These
      results are compared against available feline ANF data, and possible effects of
      individual parameters are discussed.

PMID- 20033250
TI  - Lowering missing item values in quality-of-life questionnaires: an interventional
      study.
AB  - OBJECTIVE: Missing item values (MIV) often occur in quality-of-life (QoL)
      questionnaires. This study aimed to examine whether the use of introductory
      exemplary questions reduces the number of MIV and what patient-related factors
      influence effectiveness of such a QoL form training. METHODS: In a randomized
      controlled study in ten primary care practice settings, a total of 215
      consecutively recruited patients with at least one chronic disease were requested
      to complete the Medical Outcomes Study 36 Items Short Form (SF-36) questionnaire,
      German version 1.0. Prior to filling out the QoL form, a sample of randomly
      selected patients answered three simple written questions similar in wording and
      appearance to the original SF-36 questionnaire. RESULTS: In total, 126 (58.6%)
      patients completed the SF-36 questionnaire without MIV. Despite MIV the forms of
      46 (21.4%) patients were still computable, i.e., scoring of scales was possible
      after use of the standardized SF-36 imputation algorithm. After the imputation
      procedure, MIV significantly hampered generating computable sum scales in 29
      (26.6%) of the control group and 14 (13.2%) of the interventional group (P <
      0.05). A univariate analysis suggested no evidence that the number of MIV was
      reduced by the intervention. However, intervention led to a significant decrease
      of MIV in males but not in females. The education status affected the number of
      missing data independent of intervention. CONCLUSION: This cross-sectional study
      showed that the prior use of three self-created questions similar in wording and
      appearance to the SF-36 questionnaire significantly reduces MIV in male patients.
      School qualification of QoL respondents inversely correlated with the number of
      questionnaire MIV, but independent of education status all subjects did benefit
      from the QoL form training.

PMID- 20033251
TI  - Climate change and mental health: a causal pathways framework.
AB  - OBJECTIVES: Climate change will bring more frequent, long lasting and severe
      adverse weather events and these changes will affect mental health. We propose an
      explanatory framework to enhance consideration of how these effects may operate
      and to encourage debate about this important aspect of the health impacts of
      climate change. METHODS: Literature review. RESULTS: Climate change may affect
      mental health directly by exposing people to trauma. It may also affect mental
      health indirectly, by affecting (1) physical health (for example, extreme heat
      exposure causes heat exhaustion in vulnerable people, and associated mental
      health consequences) and (2) community wellbeing. Within community, wellbeing is
      a sub-process in which climate change erodes physical environments which, in
      turn, damage social environments. Vulnerable people and places, especially in low
      income countries, will be particularly badly affected. CONCLUSIONS: Different
      aspects of climate change may affect mental health through direct and indirect
      pathways, leading to serious mental health problems, possibly including increased
      suicide mortality. We propose that it is helpful to integrate these pathways in
      an explanatory framework, which may assist in developing public health policy,
      practice and research.

PMID- 20033252
TI  - Workplace smoking restrictions: smoking behavior and the intention to change
      among continuing smokers.
AB  - OBJECTIVES: In this study, the association between three levels of workplace
      smoking restrictions and smoking behavior and variables related to the intention
      to quit among continuing smokers was examined. METHODS: Adult smokers were
      recruited from consecutive patients attending a random sample of 34 general
      medical practices from a pre-defined, north-eastern German region. Self-reported
      data were gathered in the waiting room by questionnaire. Cross-sectional data of
      1,012 employees were analyzed using ordered logistic regression analyses.
      RESULTS: Among the sample, 12% reported a smoke-free workplace, 51% had partial,
      and 37% no smoking restrictions. Daily cigarette consumption was lower when there
      were higher levels of restriction. No association was found between smoking
      restrictions and previous attempts to quit, nicotine dependence, or indicators of
      adjusted inhalation to compensate for the lower number of cigarettes (e.g. puffs
      per cigarette, darker coloring of filter). Smoking restrictions were positively
      associated with single psychological measures related to the intention to quit.
      CONCLUSION: Employees who continue to smoke may benefit from workplace smoking
      restrictions in terms of reduced, active smoke exposure and psychological effects
      increasing their readiness to quit.

PMID- 20033253
TI  - Depressive symptoms among adults 18-69 years in Italy: results from the Italian
      behavioural risk factor surveillance system, 2007.
AB  - BACKGROUND: Little is known about the prevalence of depressive symptoms in the
      Italian general population, nor about help-seeking behaviours among those with
      depressive symptoms. METHODS: We used 2007 data from PASSI, the Italian
      behavioural risk factor surveillance system, based on telephone interviews of
      residents aged 18- 69 years. A modified version of the Patient Health
      Questionnaire-2 was used to explore the presence of depressive symptoms. Those
      with symptoms were asked about whether they had sought help. Association of
      depressive symptoms with risk factors and self-perceived health was evaluated.
      RESULTS: 9.4% of the interviewees met the case definition. Risk factors included
      older age, female sex, low educational attainment, unemployment, financial
      problems and chronic illnesses. Of those for whom information on help-seeking was
      available, 47.2% did not seek any help. Depressive symptoms were associated with
      poorer self-perceived health. CONCLUSION: Population-based surveillance systems
      tracking the prevalence of depressive symptoms and associated risk factors and
      behaviours may offer needed information for planning, implementing and evaluating
      promotion and prevention interventions capable of reducing the number of people
      who go on to experience depressive episodes.

PMID- 20033254
TI  - Self-rated health in different social classes of Slovenian adult population:
      nationwide cross-sectional study.
AB  - OBJECTIVES: Self-rated health can be influenced by several characteristics of the
      social environment. The aim of this study was to evaluate the relationship
      between self-rated health and self-assessed social class in Slovenian adult
      population. METHODS: The study was based on the Countrywide Integrated Non
      communicable Diseases Intervention Health Monitor database. During 2004,
      8,741/15,297 (57.1%) participants aged 25-64 years returned posted self
      administered questionnaire. Logistic regression was used to determine unadjusted
      and adjusted estimates of association between poor self-rated health and self
      assessed social class. RESULTS: Poor self-rated health was reported by 9.6% of
      participants with a decrease from lower to upper-middle/upper self-assessed
      social class (35.9 vs. 3.7%). Logistic regression showed significant association
      between self-rated health and all self-assessed social classes. In an adjusted
      model, poor self-rated health remained associated with self-assessed social class
      (odds ratio for lower vs. upper-middle/upper self-assessed social class 4.23, 95%
      confidence interval 2.46-7.25; P < 0.001). CONCLUSIONS: Our study confirmed
      differences in the prevalence of poor self-rated health across self-assessed
      social classes. Participants from lower self-assessed social class reported poor
      self-rated health most often and should comprise the focus of multisectoral
      interventions.

PMID- 20033256
TI  - Effect of endogenous and synthetic antioxidants on hydrogen peroxide-induced
      guinea-pig colon contraction.
AB  - OBJECTIVES AND DESIGN: The effects of the endogenous antioxidant alpha-lipoic
      acid on guinea pig colon smooth muscle contraction (Gpcc) induced by hydrogen
      peroxide were examined. Having previously shown that the histone deacetylase
      (HDAC) benzamide inhibitor MGCD0103 inhibits guinea-pig smooth muscle
      contraction, as do various sulfur-containing antioxidants, we asked whether
      hybrid compounds possessing both alpha-lipoic acid-derived antioxidant properties
      and HDAC inhibitory activity could inhibit Gpcc. MATERIALS AND METHODS: Guinea
      pig colon (Gpc) was incubated at 37 degrees C with Krebs buffer; the four
      stimulants-hydrogen peroxide, carbachol, histamine, and sodium fluoride-were
      added independently. The response to each stimulant alone was compared with that
      in the presence of each of the test compounds: MGCD0103, alpha-lipoic acid, and
      two of their hybrids, UCL M084 and UCL M109. RESULTS: NaF (10 mM), carbachol
      (0.05 microM), histamine (0.1 microM), and hydrogen peroxide (1 microM) produced
      Gpcc of about 50-60% above basal level. With the exception of MGCD0103 against
      hydrogen peroxide, all four test compounds at 1 microM-MGCD0103, alpha-lipoic
      acid, UCL M084, and UCL M109-produced a significant inhibition of 35-60% of Gpcc
      induced by hydrogen peroxide, NaF, and carbachol, although none reduced histamine
      or ovalbumin-induced Gpcc. Benzalkonium chloride (Bcl), a G-protein inhibitor,
      reduced the hydrogen peroxide-induced Gpcc by 35%. CONCLUSIONS: Contraction by
      stimulants used to induce Gpcc is known to involve G-proteins. All four test
      compounds-MGCD0103, alpha-lipoic acid and two of their hybrids, UCL M084 and UCL
      M109-reduced Gpcc induced by NaF and carbachol, suggesting that G-protein pathway
      involvement is relevant to the action of the test compounds, as is also indicated
      by the Bcl-induced inhibition of hydrogen peroxide-induced contractions.
      Additionally, alpha-lipoic acid and the two hybrids showed >30% inhibition of
      hydrogen peroxide-induced contractions, consistent with the antioxidant
      properties of the 1,2-dithiolane ring.

PMID- 20033255
TI  - Differences in tobacco use between Canada and the United States.
AB  - OBJECTIVES: This study explores differences in who smokes (smoker type) and
      exposure to smoking (pack-years) between Canada and the US. Both countries have
      policies to limit the number of smokers and smoking-related deaths. METHODS: This
      research uses The Joint Canada/United States Survey of Health (JCUSH) and employs
      multinomial logistic regression and ordinary least squares regression. RESULTS:
      In Canada, native-born, young, White males without a degree, with poor health and
      who had been previously married predominate in smoking. This profile is the same
      for the US. However, different characteristics predict exposure to smoking for
      the two countries. Native-born males without a degree, with poor health and who
      had been previously married smoked more cigarettes per day in Canada. For the US,
      younger individuals smoked more cigarettes per day. CONCLUSIONS: If countries
      want to focus on limiting the number of new cases of smokers, the target
      population is different from the target population that should be used if
      countries are interested in converting smokers into non-smokers, based on the
      demographic analyses presented.

PMID- 20033257
TI  - El-Sayed K. Assem (1932-2009).

PMID- 20033258
TI  - Measurement of signs of chemical shift differences between ground and excited
      protein states: a comparison between H(S/M)QC and R1rho methods.
AB  - Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR spectroscopy has
      emerged as a powerful tool for quantifying the kinetics and thermodynamics of
      millisecond exchange processes between a major, populated ground state and one or
      more minor, low populated and often invisible 'excited' conformers. Analysis of
      CPMG data-sets also provides the magnitudes of the chemical shift difference(s)
      between exchanging states (|Deltavarpi|), that inform on the structural
      properties of the excited state(s). The sign of Deltavarpi is, however, not
      available from CPMG data. Here we present one-dimensional NMR experiments for
      measuring the signs of (1)H(N) and (13)C(alpha) Deltavarpi values using weak off
      resonance R (1rho ) relaxation measurements, extending the spin-lock approach
      beyond previous applications focusing on the signs of (15)N and (1)H(alpha) shift
      differences. The accuracy of the method is established by using an exchanging
      system where the invisible, excited state can be converted to the visible, ground
      state by altering conditions so that the signs of Deltavarpi values obtained from
      the spin-lock approach can be validated with those measured directly. Further,
      the spin-lock experiments are compared with the established H(S/M)QC approach for
      measuring the signs of chemical shift differences. For the Abp1p and Fyn SH3
      domains considered here it is found that while H(S/M)QC measurements provide
      signs for more residues than the spin-lock data, the two different methodologies
      are complementary, so that combining both approaches frequently produces signs
      for more residues than when the H(S/M)QC method is used alone.

PMID- 20033259
TI  - Mortality in 272 European regions, 2002-2004. An update.
AB  - This paper presents a comprehensive update of life expectancy and mortality in
      2002-2004 in the modern European Union (EU-27) and EFTA countries. We focus on
      causes of death at younger ages (0-64 year). EUROSTAT delivered updated
      population numbers and mortality data by sex, age and cause of death for 272 NUTS
      2 regions. We compared mortality by life tables, cause decomposition life tables
      and age standardized rates. Gini coefficients estimated inequity of death rates
      over the regions. Life expectancy at birth in the EU-27 was 75.1 years (men) and
      81.3 years (women). The difference between the 10th and 90th percentile of 272
      regions was 8.0 (men) and 5.6 years (women). Men lived 6.1 years shorter in the
      new member states (NMS, new members since 2004) than in the EU-15 (members before
      2004), women 3.9 years. 60% (men) and 33% (women) of the differences in life
      expectancy between EU 15 and NMS were explained by mortality under age 65. The
      main causes explaining differences in life expectancy were ischemic and other
      heart disease, stroke, alcohol related mortality, lung cancer and injuries. The
      fraction of ill defined causes of death was large and very variable between
      countries. Mortality differences in the EU-27 are dominated by smoking, alcohol,
      diseases related to diet and a sedentary lifestyle, unsafe roads and differences
      in health care performance. Closing the health gap is feasible and ought to be a
      major target of the European Union, but monitoring will need better registration
      of causes of death.

PMID- 20033260
TI  - Nanostructured chitosan-surfactant matrices as polyphenols nanocapsules template
      with zero order release kinetics.
AB  - Nanostructured membranes and films of cationic surfactant-chitosan with tannic
      acid as polyphenol model were obtained by phase inversion method. The membranes
      were investigated by Attenuated Total Reflectance Fourier Transform InfraRred, X
      Ray Diffraction, Scanning Electron Microscopy and Thermogravimetry, and the films
      topography was analysed by Atomic Force Microscopy. The analysis reveals that the
      interactions at the molecular level between cationic CTAB surfactant and cationic
      chitosan polymer strive to weaken membrane stability, whereas, the tannic acid is
      favoured to cluster with CTAB and diminish the membrane thermodynamic
      instability. The nanocapsules formed, with dimensions in the range of 16.35-27.68
      nm, are congregating in clusters having dimensions in the domain of 50-300 nm.
      The layers resulted from these nanostructures arrangement constitute a surfactant
      chitosan matrix with tannic acid suitable for drug controlled release with zero
      order kinetics.

PMID- 20033261
TI  - Ibuprofen-loaded poly(epsilon-caprolactone) layered silicate nanocomposites
      prepared by hot melt extrusion.
AB  - Ibuprofen loaded poly(epsilon-caprolactone) (PCL) layered silicate nanocomposites
      were prepared by hot-melt extrusion. The morphology and extent of dispersion of
      ibuprofen and layered silicate was studied using a combination of wide-angle X
      ray diffraction (WAXD), field emission scanning electron microscopy (FESEM) and
      high resolution transmission electron microscopy (HRTEM). Exhaustive examination
      across the length scales revealed the composite to have both an intercalated and
      exfoliated morphology. The ibuprofen was well dispersed and distributed
      throughout the PCL matrix. Most significantly, the static tensile and dynamic
      mechanical properties of PCL can be manipulated as a function of nanoclay loading
      and is dependent on the aspect ratio of clay platelets. The glass transition of
      PCL increased by up to 16 degrees C on addition of nanoclay, as determined from
      dynamic mechanical thermal analysis (DMTA). This behaviour was attributed to the
      constrained mobility of PCL chains intercalated between clay platelets and to the
      tethering of PCL chains by hydrogen bonding with platelet edges. As a
      consequence, PCL crystallisation was inhibited and confirmed from non-isothermal
      crystallisation experiments using differential scanning calorimetry (DSC). The
      fraction of PCL that was crystalline (X(c)) decreased by 15% on addition of
      ibuprofen and nanoclay, although the temperature of crystallisation (T(c)) did
      not change significantly. The dissolution of ibuprofen from PCL can be retarded
      by addition of layered silicates (nanoclays) to the polymer matrix.

PMID- 20033262
TI  - Preclinical investigation of tolerance and antitumour activity of new
      fluorodeoxyglucose-coupled chlorambucil alkylating agents.
AB  - Our strategy is to increase drug accumulation in target tumour cells using
      specific "vectors" tailored to neoplastic tissue characteristics, which ideally
      are not found in healthy tissues. The aim of this work was to use 2-fluoro-2
      deoxyglucose (FDG) as a drug carrier, in view of its well-known accumulation by
      most primary and disseminated human tumours. We had previously selected two FDG
      cytotoxic conjugates of chlorambucil (CLB), i.e. compounds 21a and 40a, on the
      basis of their in vitro profiles. Here we investigated the antitumour profile and
      tolerance of these compounds in vitro and in vivo in two murine cell lines of
      solid tumours. In vitro, we found that micromolar concentrations of compounds 21a
      and 40a inhibited proliferation of B16F0 and CT-26 cell lines. Interestingly,
      compounds 21a and 40a were found to act at different levels in the cell cycle: S
      and subG1 accumulation for 21a and G2 accumulation for 40a. In vivo, a single
      dose-finding study to select the Maximum Tolerated Dose (MTD) by the
      intraperitoneal route (IP) showed that the two peracetylated glucoconjugates of
      CLB were less toxic than CLB itself. When given to tumour-bearing mice (melanoma
      and colon carcinoma models), according to a "q4d * 3" schedule (i.e., three doses
      at 4-day intervals) both compounds demonstrated a promising antitumour activity,
      with Log Cell Kill (LCK) values higher than 1.3 in both B16F0 and CT-26 models.
      Hence compounds 21a and 40a are good candidates for further works to develop new
      highly active antineoplastic compounds.

PMID- 20033263
TI  - Comparative analysis of an experimental subcellular protein localization assay
      and in silico prediction methods.
AB  - The subcellular localization of a protein can provide important information about
      its function within the cell. As eukaryotic cells and particularly mammalian
      cells are characterized by a high degree of compartmentalization, most protein
      activities can be assigned to particular cellular compartments. The
      categorization of proteins by their subcellular localization is therefore one of
      the essential goals of the functional annotation of the human genome. We
      previously performed a subcellular localization screen of 52 proteins encoded on
      human chromosome 21. In the current study, we compared the experimental
      localization data to the in silico results generated by nine leading software
      packages with different prediction resolutions. The comparison revealed striking
      differences between the programs in the accuracy of their subcellular protein
      localization predictions. Our results strongly suggest that the recently
      developed predictors utilizing multiple prediction methods tend to provide
      significantly better performance over purely sequence-based or homology-based
      predictions.

PMID- 20033264
TI  - Changing spousal roles and their effect on recovery in gamblers anonymous:
      GamAnon, social support, wives and husbands.
AB  - This paper examines changing spousal roles and their effects upon recovery in
      Gamblers Anonymous (GA). It is based upon a qualitative study designed to gage
      uniformity as well as variations in approaches to recovery in GA. Interviews were
      conducted with 39 GA members (26 men, 13 women; mean age 56.5 years). Though the
      study was based in the Toronto area, only 13 interviews involved participants
      from that region. Phone interviews were conducted with GA members from various
      regions of both Canada and the US. GamAnon, GA's sister fellowship, has been
      designed for anyone affected seriously by someone's gambling problem. In
      practice, GamAnon comprises mostly women--spouses of male GA members--who
      traditionally have taken a keen interest in the ways in which their husbands
      achieve and maintain abstinence from gambling. Changing spousal roles have led to
      fewer women joining GamAnon, as many opt instead to part with troubled spouses.
      As well, more women are attending GA than in the past, typically with husbands
      who are disinclined to join GamAnon. All of this has drastically altered how GA
      members pursue recovery. These changes and their implications are discussed.

PMID- 20033265
TI  - Determination of the beta-glucosidase activity in different soils by pre
      capillary enzyme assay using capillary electrophoresis with laser-induced
      fluorescence detection.
AB  - Enzyme activities can provide indication for quantitative changes in soil organic
      matter (SOM). It is known that the activities of most enzymes increase as native
      SOM content reflecting larger microbial communities and stabilization of enzymes
      on humic materials. Beta-glucosidase (beta-Glu) activities have been frequently
      used as indicators of changes in quantity and quality of SOM. In this study we
      propose a simple and very sensitive method, which has lower limit of detection
      compared with classic spectrophotometric method with the aim of determinate the
      beta-Glu activity in soil samples using Fluorescein mono-beta-D-glucopyranoside
      (FMGlc) as a substrate. The fluorescein released by the enzymatic reaction was
      quantified by capillary electrophoresis-laser induced fluorescence (CE-LIF)
      method. The background electrolyte (BGE) consisted in 40 mM phosphate buffer, pH
      6. The LOD and LOQ for fluorescein were 1.3 10(-7) mg mL(-1) and 6.4 10(-6) mg
      mL(-1), respectively. This work deals with the minimization of the mixture for
      the enzymatic reaction and with the optimization conditions of CE separation. To
      the best of our knowledge, this is the first time that an enzymatic activity was
      detected in soil using CE-LIF system.

PMID- 20033266
TI  - Studies on the interactions of 2, 4-dinitrophenol and 2, 4-dichlorphenol with
      trypsin.
AB  - The interactions of 2, 4-dinitrophenol and 2, 4-dichlorphenol with trypsin were
      investigated by fluorescence, synchronous fluorescence, and three-dimensional
      fluorescence spectra techniques under physiological pH 7.40. The 2, 4
      dinitrophenol and 2, 4-dichlorphenol effectively quenched the intrinsic
      fluorescence of trypsin via static quenching. The process of binding 2, 4
      dinitrophenol and 2, 4-dichlorphenol with trypsin was a spontaneous molecular
      interaction procedure. The electrostatic repulsion does favor the interaction
      between 2, 4-DNP and trypsin. However, the interaction of 2, 4-DCP and trypsin
      can be explained on the basis of hydrogen bonding and van der Waals. The results
      of synchronous fluorescence spectroscopy and three-dimensional fluorescence
      spectra indicated that the structure of these trytophan and tyrosine residues
      environments were altered by 2, 4-DNP and 2, 4-DCP.

PMID- 20033267
TI  - Visualizing reproduction: a cultural history of early-modern and modern medical
      illustrations.
AB  - Written as a response to a conference exhibition of medical illustrations of
      reproduction, this article considers the gains of an interdisciplinary study of
      medical illustration to both historians and medics. The article insists that we
      should not only be attuned to the cultural work that such representations perform
      but also that such illustrations are the product of material medical practices
      and the often humane impulses that drive them.

PMID- 20033268
TI  - Production of synthetic methionine-free and synthetic methionine-limited alpha
      casein: protein foodstuff for patients with homocystinuria due to cystathionine
      beta-synthase deficiency.
AB  - The aim of this study was to evaluate the possibility that synthetic forms of
      methionine-free alpha-casein and methionine-limited alpha casein could be
      produced by recombinant means to form the basis for developing an industrial
      scale process for the provision of a foodstuff suitable for patients with
      homocystinuria due to cystathionine beta-synthase (CBS) deficiency. As a first
      step, two forms of alpha casein gene, encoding methionine-free alpha casein
      (Fcas) or a methionine-limited alpha casein (Mcas), were synthesised and
      expressed in Escherichia coli. Using the overexpression vector pET28a, both genes
      were highly expressed in E. coli in soluble form as well as in inclusion bodies.
      The two recombinant proteins were purified by the one step methods using the
      fused His-tag and the Ni(2+)column and validated by Western blot analysis. This
      work paves the way for industrial-scale production of proteins suitable for
      patients with homocystinuria due to CBS deficiency.

PMID- 20033269
TI  - Fractalkine as an important target of aspirin in the prevention of atherogenesis
      : Editorial to: "Aspirin inhibits fractalkine expression in atherosclerotic
      plaques and reduces atherosclerosis in ApoE gene knockout mice" by H. Liu et al.

PMID- 20033270
TI  - Antiplatelet and anticoagulant therapies in acute coronary syndromes.
AB  - The combination of aspirin and clopidogrel is the mainstay antiplatelet therapy
      for acute coronary syndromes (ACS). However, the dosing of aspirin, the dosing of
      clopidogrel, the timing of clopidogrel initiation as well as the duration of
      clopidogrel therapy remain controversial matters. Clopidogrel resistance is an
      emerging concept with potential clinical implications. In the era of clopidogrel
      and bivalirudin, the role of glycoprotein IIb/IIIa antagonists is being
      challenged, yet they are still indicated in a select high-risk population.
      Concerning anticoagulant use in ACS, newer agents, bivalirudin and fondaparinux,
      have improved outcomes in comparison to heparin in patients managed with an
      invasive or conservative strategy, respectively. Combining multiple antiplatelet
      agents and an anticoagulant is the standard of care for ACS.

PMID- 20033271
TI  - Extracting functional components of neural dynamics with Independent Component
      Analysis and inverse Current Source Density.
AB  - Local field potentials have good temporal resolution but are blurred due to the
      slow spatial decay of the electric field. For simultaneous recordings on regular
      grids one can reconstruct efficiently the current sources (CSD) using the inverse
      Current Source Density method (iCSD). It is possible to decompose the resultant
      spatiotemporal information about the current dynamics into functional components
      using Independent Component Analysis (ICA). We show on test data modeling
      recordings of evoked potentials on a grid of 4 * 5 * 7 points that meaningful
      results are obtained with spatial ICA decomposition of reconstructed CSD. The
      components obtained through decomposition of CSD are better defined and allow
      easier physiological interpretation than the results of similar analysis of
      corresponding evoked potentials in the thalamus. We show that spatiotemporal ICA
      decompositions can perform better for certain types of sources but it does not
      seem to be the case for the experimental data studied. Having found the
      appropriate approach to decomposing neural dynamics into functional components we
      use the technique to study the somatosensory evoked potentials recorded on a grid
      spanning a large part of the forebrain. We discuss two example components
      associated with the first waves of activation of the somatosensory thalamus. We
      show that the proposed method brings up new, more detailed information on the
      time and spatial location of specific activity conveyed through various parts of
      the somatosensory thalamus in the rat.

PMID- 20033272
TI  - Changes in brain activity during the observation of TV commercials by using EEG,
      GSR and HR measurements.
AB  - In this study we were interested to analyse the brain activity occurring during
      the "naturalistic" observation of commercial ads intermingled in a random order
      within a documentary. In order to measure both the brain activity and the
      emotional engage of the 15 healthy subjects investigated, we used simultaneous
      EEG, Galvanic Skin Response (GSR), Heart Rate (HR) recordings during the whole
      experiment. We would like to link significant variation of EEG, GSR, HR and Heart
      Rate Variability (HRV) measurements with the memory and pleasantness of the
      stimuli presented, as resulted successively from the subject's verbal interview.
      In order to do that, different indexes were employed to summarize the cerebral
      and autonomic measurements performed. Such indexes were used in the statistical
      analysis, performed with the use of Analysis of Variance (ANOVA) and z-score
      transformation of the estimated cortical activity by solving the associated EEG
      inverse problem. The results are summarized as follows: (1) in the population
      analyzed, the cortical activity in the theta band elicited during the observation
      of the TV commercials that were remembered is higher and localized in the left
      frontal brain areas when compared to the activity elicited during the vision of
      the TV commercials that were forgotten (p < 0.048). Same increase in the theta
      activity occurred during the observation of commercials that were judgment
      pleasant when compared with the other (p < 0.042). Differences in cortical
      activity were also observed for the gamma activity, bilaterally in frontal and
      prefrontal areas. (2) the HR and HRV activity elicited during the observation of
      the TV commercials that were remembered or judged pleasant is higher than the
      same activity during the observation of commercials that will be forgotten (p <
      0.001 and p < 0.048, respectively for HR and HRV) or were judged unpleasant (p <
      0.042 and p < 0.04, respectively for HR and HRV). No statistical differences
      between the level of the GSR values were observed across the experimental
      conditions. In conclusion, the TV commercials proposed to the population analyzed
      have increased the HR values and the cerebral activity mainly in the theta band
      in the left hemisphere when they will be memorized and judged pleasant. Further
      research with an extended set of subjects will be necessary to further validate
      the observations reported in this paper. However, these conclusions seems
      reasonable and well inserted in the already existing literature on this topic
      related to the HERA model.

PMID- 20033273
TI  - Differences in aggressive behavior and DNA copy number variants between BALB/cJ
      and BALB/cByJ substrains.
AB  - Some BALB/c substrains exhibit different levels of aggression. We compared
      aggression levels between male BALB/cJ and BALB/cByJ substrains using the
      resident intruder paradigm. These substrains were also assessed in other tests of
      emotionality and information processing including the open field, forced swim,
      fear conditioning, and prepulse inhibition tests. We also evaluated single
      nucleotide polymorphisms (SNPs) previously reported between these BALB/c
      substrains. Finally, we compared BALB/cJ and BALB/cByJ mice for genomic deletions
      or duplications, collectively termed copy number variants (CNVs), to identify
      candidate genes that might underlie the observed behavioral differences. BALB/cJ
      mice showed substantially higher aggression levels than BALB/cByJ mice; however,
      only minor differences in other behaviors were observed. None of the previously
      reported SNPs were verified. Eleven CNV regions were identified between the two
      BALB/c substrains. Our findings identify a robust difference in aggressive
      behavior between BALB/cJ and BALB/cByJ substrains, which could be the result of
      the identified CNVs.

PMID- 20033274
TI  - Catechol-o-methyltransferase genotype and childhood trauma may interact to impact
      schizotypal personality traits.
AB  - We attempt to identify gene by childhood abuse interactions which predispose to
      the development of schizotypal traits in a familial bipolar disorder (BD) sample.
      Self-report measures of schizotypal personality traits (Schizotypal Personality
      Scale) and childhood maltreatment (Childhood Trauma Questionnaire) were
      administered to 222 participants from 44 families with BD. Variants of catechol-o
      methyltransferase (COMT) and four other dopamine pathway-related genes: DRD4,
      DRD2,MAOA, and SLC6A3, were typed. BD type I (BD I) subjects scored significantly
      higher than their unaffected relatives on the Schizotypal Personality Scale. The
      val allele of the Val158 Met polymorphism of the COMT gene was associated with
      increased schizotypal personality trait scores in individuals exposed to higher
      levels of self-reported childhood trauma (p < 0.05). There was no direct effect
      of the val158met polymorphism on schizotypal personality traits. Further, no
      passive correlation between COMT genotype and childhood trauma was found. We
      raise the possibility that genetically-driven variation in COMT may interact with
      childhood trauma to contribute to the risk of developing schizotypal personality
      traits.

PMID- 20033275
TI  - Matched ascertainment of informative families for complex genetic modelling.
AB  - Family data are used extensively in quantitative genetic studies to disentangle
      the genetic and environmental contributions to various diseases. Many family
      studies based their analysis on population-based registers containing a large
      number of individuals composed of small family units. For binary trait analyses,
      exact marginal likelihood is a common approach, but, due to the computational
      demand of the enormous data sets, it allows only a limited number of effects in
      the model. This makes it particularly difficult to perform joint estimation of
      variance components for a binary trait and the potential confounders. We have
      developed a data-reduction method of ascertaining informative families from
      population-based family registers. We propose a scheme where the ascertained
      families match the full cohort with respect to some relevant statistics, such as
      the risk to relatives of an affected individual. The ascertainment-adjusted
      analysis, which we implement using a pseudo-likelihood approach, is shown to be
      efficient relative to the analysis of the whole cohort and robust to mis
      specification of the random effect distribution.

PMID- 20033276
TI  - A randomized trial to evaluate the efficacy of a computer-tailored intervention
      to promote safer injection practices among drug users.
AB  - The aim of this study was to evaluate the efficacy of a theory-based intervention
      to increase the use of a new syringe for each injection among injection drug
      users (IDUs). Users of two needle exchange programs (NEPs) were involved. At both
      sites, participants were assigned at random to either the experimental or the
      control group. Once a week for four weeks, users reported to the NEPs where they
      logged onto a computer and received an audiovisual message. A total of 260 IDUs
      were recruited. At baseline, 52.3% of participants reported that they had not
      always used new syringes in the previous week. The results indicate that it is
      possible for IDUs to adopt safer injection practices. One month after the
      intervention began, participants in the experimental group were using fewer dirty
      syringes compared to the control group (RR: 0.47 CI(95%) 0.28-0.79; P = .004).
      This short-term effect was no longer present 3 months later.

PMID- 20033277
TI  - Social grants, welfare, and the incentive to trade-off health for income among
      individuals on HAART in South Africa.
AB  - South Africa's government disability grants are considered important in providing
      income support to low-income AIDS patients. Indeed, anecdotal evidence suggests
      that some individuals may opt to compromise their health by foregoing Highly
      Active Antiretroviral Treatment (HAART) to remain eligible for the grant. In this
      study, we examined the disability grant's importance to individual and household
      welfare, and the impact of its loss using a unique longitudinal dataset of HAART
      patients in Khayelitsha, Cape Town. We found that grant loss was associated with
      sizeable declines in income and changes in household composition. However, we
      found no evidence of individuals choosing poor health over grant loss. Our
      analysis also suggested that though the grants officially target those too sick
      to work, some people were able to keep grants longer than expected, and others
      received grants while employed. This has helped cushion people on HAART, but
      other welfare measures need consideration.

PMID- 20033278
TI  - Integrated assessment of brick kiln emission impacts on air quality.
AB  - This paper presents monitoring results of daily brick kiln stack emission and the
      derived emission factors. Emission of individual air pollutant varied
      significantly during a firing batch (7 days) and between kilns. Average emission
      factors per 1,000 bricks were 6.35-12.3 kg of CO, 0.52-5.9 kg of SO(2) and 0.64
      1.4 kg of particulate matter (PM). PM emission size distribution in the stack
      plume was determined using a modified cascade impactor. Obtained emission factors
      and PM size distribution data were used in simulation study using the Industrial
      Source Complex Short-Term (ISCST3) dispersion model. The model performance was
      successfully evaluated for the local conditions using the simultaneous ambient
      monitoring data in 2006 and 2007. SO(2) was the most critical pollutant,
      exceeding the hourly National Ambient Air Quality Standards over 63 km(2) out of
      the 100-km(2) modelled domain in the base case. Impacts of different emission
      scenarios on the ambient air quality (SO(2), PM, CO, PM dry deposition flux) were
      assessed.

PMID- 20033279
TI  - Autochthonous clams monitoring of Ganzirri Lake (Sicily).
AB  - Two autochthonous clams, Venerupis aurea laeta and Cerastoderma edule/glaucum,
      collected for a period of 1 year, from May 2007 to January 2008, were studied in
      the Cape Peloro lagoon. On the samples, it was evaluated the presence of
      pathogenic microorganisms and proteins, lipids and yield edible part were
      determined. It was evaluated the concentration of mineral elements (Cd, Cu, Mn,
      Se, Pb, Zn) and organic contaminants (?DDT and PCBs). Salmonella is never present
      in any sample. Total and faecal coliform values have always been under law limits
      for alive bivalves mussels production and sale. Zn, Cu, Cd and Pb levels were
      found in clams where they are slightly lower too. Both species do not show
      significant changes for Mn and Se. DDT and PCBs traces were discovered in
      Ganzirri Lake' samples, but in all observed cases, they were below law limits. As
      a result of all these observations, it is clear that, in recent years, the
      bivalve's use of Ganzirri Lake does not denote toxicological risk to human
      health.

PMID- 20033280
TI  - Determination of cadmium and lead in human biological samples by spectrometric
      techniques: a review.
AB  - The analysis of human biological samples, such as blood, urine, nails, and hair,
      is generally used for the verification of human exposure to toxic metals. In this
      review, various spectrometric methods for the determination of cadmium and lead
      in biological samples are discussed and compared. Several spectrometric
      techniques are presented and discussed with respect to various characteristics
      such as sensitivity, selectivity, and cost. Special attention is drawn to the
      procedures for digestion prior to the determination of cadmium and lead in hair,
      nails, blood, and urine.

PMID- 20033281
TI  - Influence of processing parameters on VOC emission from particleboards.
AB  - Volatile organic compound (VOC) emissions from furnishings have created a major
      indoor air pollution problem in China. The aim of this study was to investigate
      the VOC emission of larch particleboard under different processing conditions.
      VOCs collection chamber, parts per billion VOC monitor, and gas chromatography
      mass spectrometer were used to analyze the VOC components and quantities. The
      results were shown as follows: (1) concentration and emission rate of VOCs were
      significantly affected by hot-pressing temperature and time. With the increase of
      hot-pressing temperature and time, both the earlier emission concentration and
      the amount of total volatile organic compounds increased. (2) The composition of
      VOCs was also influenced by temperature and time, especially the variety of
      terpene, benzene, and derivative. The existence and quantities of esters were
      still the main components of VOCs emissions.

PMID- 20033282
TI  - Monitoring trace metals in different tissues of Cyprinus carpio from the Indus
      River in Pakistan.
AB  - This replicated 4*2 factorial study investigated the bioaccumulation of selected
      metals (Mn, Pb, Zn, Hg and Cr) in four tissues (gills, liver, muscle and skin) of
      common carp (Cyprinus carpio) domiciled in two sites (upstream and downstream) of
      Indus River in Mianwali district of Pakistan. The data were statistically
      compared for the main effects of the site and fish organs and their interaction
      on the bioaccumulation pattern of these metals in fish organs at P<0.05. It
      appeared that the fish sampled from downstream had higher trace metals than the
      fish from upstream. Significant differences between fish organs were observed for
      these trace metals (P<0.001). The fish showed higher bioaccumulation of vital
      metals like Zn and lower bioaccumulation for the toxic metals like Pb. The gills
      had the highest metal load followed by liver, skin and muscles. High
      concentrations of Mn, Hg and Cr were observed in different fish organs as
      compared to the WHO and Federal Environmental Protection Agency standards for
      food fish. However, the mean concentration of Pb and Zn were under the
      permissible limits of food fish. It implies that higher levels of Mn, Hg and Cr
      in fish muscles would have detrimental effects on the health of fish consumers
      such as pregnant women, children and elderly people of this study area.

PMID- 20033283
TI  - Investigation of heavy metals in sediments and Manila clams Ruditapes
      philippinarum from Jiaozhou Bay, China.
AB  - Manila clams (Ruditapes philippinarum) and sediments were collected bimonthly
      during 2007 at five locations in Jiaozhou Bay near Qingdao, China, to determine
      heavy metal concentrations and to assess the validation of R. philippinarum as a
      metal biomonitor. Concentrations of heavy metals in clam soft tissues ranged
      between 0.75 and 3.31, 0.89 and 15.20, 5.70 and 26.03, 52.12 and 110.33, 10.30
      and 72.34, 9.64 and 28.60, and 3.15 and 52.75 MUg g(-1) dry weight for Cd, Pb,
      Cu, Zn, Mn, Cr, and Ni, respectively. Most of the highest values occurred at the
      northeast bay and the lowest values occurred at the western part. Regarding
      seasonal variation, relatively high tissue metal concentrations were observed
      during October or December. A similar pattern was also found in habitat
      sediments. There was a strong correlation between the concentrations of Cd, Pb,
      Zn, Mn, Cr, and Ni in soft tissues and surrounding sediments. It is indicated
      that R. philippinarum could be used as a biomonitor for heavy metal contamination
      in Jiaozhou Bay.

PMID- 20033284
TI  - Acute aquatic toxicity of western juniper (Juniperus occidentalis) foliage and
      Port Orford cedar (Chamaecyparis lawsoniana) heartwood oils.
AB  - Recently, interest has developed for using essential oils from Western juniper
      (Juniperus occidentalis) foliage and Port Orford cedar (Chamaecyparis lawsoniana)
      heartwood in commercial products such as pest repellents and cosmetics. In order
      to gauge the relative toxicological risk that these oils pose to freshwater and
      marine organisms, the acute aquatic toxicity of these oils was evaluated using
      OPPTS guidelines to the cladoceran Daphnia magna, the rainbow trout Oncorhynchus
      mykiss and the green alga Selenastrum capricornutum. For western juniper foliage
      oil, no toxicity was exhibited toward D. magna or O. mykiss, even at 5.0 mg/L
      (the highest concentration tested and limit of solubility). For toxicity to S.
      capricornutum using algal cell density, the 72 and 96 h EC50 value was 1.7 mg/L
      and the no observable effect concentration (NOEC) was 0.63 mg/L. For Port Orford
      cedar heartwood oil, no toxicity was exhibited toward O. mykiss or S.
      capricornutum, even at 5.0 mg/L (the highest concentration tested and limit of
      solubility). The 48-h D. magna EC50 value was 1.9 mg/L; the NOEC values for algal
      cell density were 1.25 mg/L (72 h) and 0.63 mg/L (96 h). In summary, this study
      shows that western juniper foliage and Port Orford cedar heartwood oils
      demonstrate little to no risk to aquatic organisms.

PMID- 20033285
TI  - Using two classification schemes to develop vegetation indices of biological
      integrity for wetlands in West Virginia, USA.
AB  - Bioassessment methods for wetlands, and other bodies of water, have been
      developed worldwide to measure and quantify changes in "biological integrity."
      These assessments are based on a classification system, meant to ensure
      appropriate comparisons between wetland types. Using a local site-specific
      disturbance gradient, we built vegetation indices of biological integrity (Veg
      IBIs) based on two commonly used wetland classification systems in the USA: One
      based on vegetative structure and the other based on a wetland's position in a
      landscape and sources of water. The resulting class-specific Veg-IBIs were
      comprised of 1-5 metrics that varied in their sensitivity to the disturbance
      gradient (R2=0.14-0.65). Moreover, the sensitivity to the disturbance gradient
      increased as metrics from each of the two classification schemes were combined
      (added). Using this information to monitor natural and created wetlands will help
      natural resource managers track changes in biological integrity of wetlands in
      response to anthropogenic disturbance and allows the use of vegetative
      communities to set ecological performance standards for mitigation banks.

PMID- 20033287
TI  - Mental model progression in learning the electron transport chain: effects of
      instructional strategies and cognitive flexibility.
AB  - This study investigated the effect of two instructional strategies, segmented and
      holistic, on the progression over time of learners' mental models toward that of
      an expert with the moderator of cognitive flexibility. Sixty-four juniors and
      seniors in a college metabolism course were randomly assigned to one of the two
      strategies for instruction on the electron transport chain. The data were
      analyzed with a repeated measures general linear model. Mental models progressed
      significantly for both strategies (p < .001), and a significant interaction was
      found between cognitive flexibility and instructional strategy on mental model
      progression (p = .02). The segmented strategy was superior for learners with
      higher cognitive flexibility but inferior to the holistic strategy for lower
      cognitive flexibility learners. Results have important implications for
      differentiating instruction on the basis of learner characteristics.

PMID- 20033288
TI  - Delayed but excellent myogenic stem cell response of regenerating geriatric
      skeletal muscles in mice.
AB  - The ability of very old animals to make new muscle after injury remains
      controversial. This issue has major implications for the regenerative potential
      of damaged geriatric human muscle, to age-related loss of muscle mass
      (sarcopenia) and to the proposed need for muscle stem cell therapy for the aged.
      To further address issues of inherent myogenic capacity and the role of host
      systemic factors in new muscle formation, whole muscle grafts were transplanted
      between geriatric (aged 27-29 months) and young (3 months) C57Bl/6J mice and
      compared with autografts in geriatric and young mice. Grafts were sampled at 5
      and 10 days for histological analysis. Inflammation and formation of new myotubes
      was strikingly impaired at 5 days in the geriatric muscle autografts. However,
      there was a strong inflammatory response by the geriatric hosts to young muscle
      grafts and geriatric muscles provoked an inflammatory response by young hosts at
      5 days. At 10 days, extensive myotube formation in geriatric muscle autografts
      (equivalent to that seen in young autografts and both other groups) confirmed
      excellent intrinsic capacity of myogenic (stem) cells to proliferate and fuse.
      The key conclusion is that a weaker chemotactic stimulus by damaged geriatric
      muscle, combined with a reduced inflammatory response of old hosts, results in
      delayed inflammation in geriatric muscle autografts. This delay is transient.
      Once inflammation occurs, myogenesis can proceed. The presence of well developed
      myotubes in old muscle autografts at 10 days confirms a very good inherent
      myogenic response of geriatric skeletal muscle.

PMID- 20033289
TI  - Computer-assisted numerical analysis of colour-group data for dereplication of
      streptomycetes for bioprospecting and ecological purposes.
AB  - Large numbers of alkaliphilic streptomycetes isolated from a beach and dune sand
      system were dereplicated manually based on aerial spore mass, colony reverse and
      diffusible pigment colours formed on oatmeal agar, and on their capacity to
      produce melanin pigments on peptone-yeast extract-iron agar. The resultant data
      were converted to their respective red, blue and green shade intensities. The
      Euclidean distances between each of the colours were calculated by considering
      red, green and blue shade intensity values as X, Y and Z coordinates in three
      dimensional space. The clusters of isolates delineated in the dendrogram
      generated using the distances were found to match those obtained by manual colour
      grouping of the isolates. A reasonable linear correlation was found between the
      colour-group and corresponding rep-PCR data. The implications of the computer
      assisted colour-grouping method for bioprospecting and ecological studies are
      discussed.

PMID- 20033290
TI  - Severe ifosfamide-induced neurotoxicity: a case report.
AB  - INTRODUCTION: Ifosfamide is an alkylating agent used in the treatment of several
      neoplasias. Ifosfamide metabolites accumulation can produce neurotoxicity, which
      sometimes manifests as a severe clinical picture. CASE DESCRIPTION: We describe
      the case of a male with a mixed cellularity subtype classical Hodgkin's lymphoma,
      treated with ifosfamide after other chemotherapy drugs failure. After the first
      Ifosfamide cycle, the patient showed severe neurological toxicity that resolved 3
      weeks later with supportive therapy. DISCUSSION: Among the risk factors described
      in the literature, our patient had previously received cisplatin chemotherapy,
      had low albumin serum levels, and had received ifosfamide as a rapid intravenous
      infusion. The management of the neurotoxicity is symptomatic although some drugs,
      like methylene blue and albumin, have also been used. CONCLUSION: This case
      highlights that clinicians should be aware of the possibility of severe
      neurological toxicity after the administration of ifosfamide and may control the
      risk factors associated.

PMID- 20033291
TI  - A cross-language study of perception of lexical stress in English.
AB  - This study investigates the question of whether language background affects the
      perception of lexical stress in English. Thirty native English speakers and 30
      native Chinese learners of English participated in a stressed-syllable
      identification task and a discrimination task involving three types of stimuli
      (real words/pseudowords/hums). The results show that both language groups were
      able to identify and discriminate stress patterns. Lexical and segmental
      information affected the English and Chinese speakers in varying degrees. English
      and Chinese speakers showed different response patterns to trochaic vs. iambic
      stress across the three types of stimuli. An acoustic analysis revealed that two
      language groups used different acoustic cues to process lexical stress. The
      findings suggest that the different degrees of lexical and segmental effects can
      be explained by language background, which in turn supports the hypothesis that
      language background affects the perception of lexical stress in English.

PMID- 20033292
TI  - False-positive newborn screening mimicking glutaric aciduria type I in infants
      with renal insufficiency.
AB  - Glutaric aciduria type I (GA I), an autosomal-recessive deficiency of glutaryl
      CoA-dehydrogenase, leads to encephalopathic crises resulting in irreversible
      neurological damage. As early diagnosis and implementation of appropriate
      treatment has significant benefit for these patients, GA I has been implemented
      in the extended newborn screening program in several countries. Screening
      parameter is glutarylcarnitine (C5DC) with its ratios. From 1 January 2005 until
      31 December 2008, 173,846 newborns were examined by neonatal screening in our
      screening center. C5DC and/or at least three C5DC/acylcarnitine ratios were
      increased in 53 newborns (0.03%) and persisted in 11 infants after recall. GA I
      was not confirmed in any of these infants, but all 11 infants were suffering from
      renal insufficiency due to congenital (5/11) or acquired (6/11) renal disease.
      C5DC was shown to be significantly associated with renal affection and was
      significantly higher in infants with congenital renal insufficiency than in those
      with acquired renal insufficiency (p = 0.011). Creatinine correlated
      significantly with C5DC (p = 0.001) and all C5DC/acylcarnitine ratios, mainly
      with C5DC/(C8 + C10), C5DC/C0, C5DC/C2, C5DC/C4, and C5DC/C8 (for all: p =
      0.001). Glutarylcarnitinemia associated with renal insufficiency has not yet been
      studied systematically. Renal damage in neonates might lead to disturbances in
      renal transporter systems of glutaric acid and its metabolites and a decreased
      excretion of C5DC, thus resulting in an increase of plasma C5DC. Therefore,
      newborns presenting with a positive screening indicating GA I may be considered
      not only to suffer from GA I but from renal insufficiency as well.

PMID- 20033293
TI  - Tyrosinemia type 1 and Angelman syndrome due to paternal uniparental isodisomy
      15.
AB  - Uniparental isodisomy arises when an individual inherits two copies of a specific
      chromosome from a single parent, which can unmask a recessive mutation or cause a
      problem of genetic imprinting. Here we describe an exceptional case in which the
      patient simultaneously presents tyrosinemia type 1 and Angelman syndrome. The
      genetic studies showed that the patient presents paternal uniparental isodisomy
      of chromosome 15, with absence of the maternal homolog. As a consequence of this
      isodisomy, the patient is homozygous for the mutation IVS12+5G>A in the FAH gene,
      located in the chromosomal region 15q23-25, causing tyrosinemia type 1. The
      mutation was inherited from his father in double dosage, whereas the mother is
      not a carrier, which implies that the recurrence risk in the family is
      negligible. On the other hand, the lack of maternal contribution causes Angelman
      syndrome, a neurodevelopmental disorder associated with a loss of maternal gene
      expression in chromosome region 15q11-q13, and more specifically, of the UBE3A
      gene. This gene shows a tissue-specific imprinting, and only the maternally
      derived allele is expressed in certain areas of the brain. We observed through a
      literature review that uniparental disomy probably occurs more frequently than
      suspected, although it is more usually detected when the uniparental disomy
      implies the appearance of a disease because of the gene imprinting or by
      reduction to homozygosity of a recessive mutation. The conclusion is that
      uniparental disomy should always be considered when more than one genetic disease
      mapping to the same chromosome is present in a patient.

PMID- 20033294
TI  - Zellweger syndrome with unusual findings: non-immune hydrops fetalis, dermal
      erythropoiesis and hypoplastic toe nails.
AB  - The peroxisomal biogenesis disorders (PBDs) comprise the Zellweger spectrum
      disorders (i.e., Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile
      Refsum disease) and rhizomelic chondrodysplasia punctata. Peroxisomal biogenesis
      disorders can be caused by mutations in any of 13 currently known PEX genes,
      which encode peroxins involved in peroxisomal protein import and/or assembly of
      the organelle. We report here on a Turkish patient who presented with unusual
      clinical findings, that included non-immune hydrops, dermal erythropoiesis and
      hypoplastic toenails, as well as common dysmorphic features of Zellweger
      syndrome. The patient has also pulmonary hypoplasia, which has been reported in
      only a few patients with Zellweger syndrome. A peroxisomal biogenesis disorder
      was confirmed by enzyme analysis and abnormal very long-chain fatty acid (VLCFA)
      profiles in plasma and fibroblast and immunofluorescence microscopy studies.
      Subsequent molecular genetic analysis revealed a homozygous c.856C>T mutation
      (R268X) in the PEX3 gene, which made this patient the third to have a defect in
      this gene. In contrast to those of the two previously reported patients, the
      cells of this patient still contained peroxisomal membrane structures (ghosts),
      seen by immunofluorescence microscopy analysis. The case presented here and the
      two previously reported cases point out that a PEX3 gene defect may present with
      fairly heterogeneous clinical findings. This case also raises a possibility that
      hydrops fetalis may be associated with a PEX3 gene defect and that peroxisomal
      disorders can be considered in the etiology of hydrops fetalis as well as other
      cell organelle disorders when one is considering yet undiscovered complementation
      groups in peroxisomal disorders.

PMID- 20033295
TI  - Increased prevalence of mutant null alleles that cause hereditary fructose
      intolerance in the American population.
AB  - Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward
      fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI).
      Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in
      suspected patients; however, the frequencies of mutant alleles can differ by
      population. Here, 153 American HFI patients with 268 independent alleles were
      analyzed to identify the prevalence of seven known HFI-causing alleles (A149P,
      A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population. Allele
      specific oligonucleotide hybridization analysis was performed on polymerase chain
      reaction (PCR)-amplified genomic DNA from these patients. In the American
      population, the missense mutations A149P and A174D are the two most common
      alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense
      mutations Delta4E4 and R59Op are the next most common alleles, with each having a
      frequency of 4%. Together, the frequencies of all seven alleles make up 65% of
      HFI-causing alleles in this population. Worldwide, these same alleles make up 82%
      of HFI-causing mutations. This difference indicates that screening for common HFI
      alleles is more difficult in the American population. Nevertheless, a genetic
      screen for diagnosing HFI in America can be improved by including all seven
      alleles studied here. Lastly, identification of HFI patients presenting with
      classic symptoms and who have homozygous null genotypes indicates that aldolase B
      is not required for proper development or metabolic maintenance.

PMID- 20033296
TI  - Diagnostic efficacy of the fluorometric determination of enzyme activity for
      Pompe disease from dried blood specimens compared with lymphocytes-possibility
      for newborn screening.
AB  - BACKGROUND: Pompe disease is a rare, autosomal-recessive disorder which results
      from a defect in the lysosomal enzyme acid alpha-glucosidase (GAA). The onset of
      this disease is highly variable, with infantile types being the most severe.
      Traditionally, lymphocytes, fibroblasts or muscle biopsies were necessary for
      enzyme activity measurement, because these materials do not express maltase
      glucoamylase (MGA) that interferes with the assay. Recently, acarbose was found
      to inhibit MGA activity selectively, so that dried blood became accessible for
      GAA assessment. AIM: To evaluate the diagnostic efficacy of GAA measurement in
      dried blood specimens (DBSs) in comparison with lymphocytes. If DBSs provided
      reliable results, the diagnosis of Pompe disease could be facilitated, and high
      throughput screening would become possible. METHODS AND RESULTS: GAA activity was
      measured in DBSs of known patients at pH 3.8 (with and without acarbose) and at
      pH 7.0. Additionally, lymphocytes were obtained from the same patients, and the
      enzyme activity was determined at pH 4 to pH 7. In total, seven infantile
      patients and 29 patients with late-onset variants were investigated. All patients
      were reliably identified by both methods. Furthermore, a simplified protocol was
      established for neonatal screening. CONCLUSION: The fluorometric technique for
      the assessment of GAA activity in DBS provides a reliable diagnosis for all
      variants of Pompe disease. The assay protocol could be simplified for neonatal
      screening, without increasing the false positive rate significantly or burdening
      the laboratory with time-consuming procedures.

PMID- 20033297
TI  - Inhibition of iron induced lipid peroxidation and antioxidant activity of Indian
      spices and Acacia in vitro.
AB  - The spices used in the Indian foods such as Star anise (Illicium verum), Bay
      leaves (Cinnamomum zeylanicum) and Cobra's saffron (Mesua ferrea), and Acacia
      (Acacia catechu), which have medicinal value, were used as test samples, to find
      their effect on in vitro lipid peroxidation (LPO). Rat liver post mitochondrial
      supernatant (PMS) in Tris HCl buffer, pH 7.4 was incubated for 0 and 1 h, with
      various test extracts in three different oxidant systems. The results show that
      addition of test samples to FeCl(3) medium at 0 h significantly stop the
      initiation of the LPO. However, the propagation phase of LPO was inhibited by
      Cobra's saffron and Acacia and not by Star anise and Bay leaves. The test samples
      also showed strong reducing power and superoxide radical scavenging activity.
      Cobra's saffron and Acacia showed the highest antioxidant activity, probably due
      to the higher polyphenol content as compared to other test samples.

PMID- 20033298
TI  - Sugars profiles of different chestnut (Castanea sativa Mill.) and almond (Prunus
      dulcis) cultivars by HPLC-RI.
AB  - Sugar profiles of different almond and chestnut cultivars were obtained by high
      performance liquid chromatography (HPLC), by means of a refractive index (RI)
      detector. A solid-liquid extraction procedure was used in defatted and dried
      samples. The chromatographic separation was achieved using a Eurospher 100-5
      NH(2) column using an isocratic elution with acetonitrile/water (70:30, v/v) at a
      flow rate of 1.0 ml/min. All the compounds were separated in 16 min. The method
      was optimized and proved to be reproducible and accurate. Generally, more than
      95% of sugars were identified for both matrixes. Sugars profiles were quite
      homogeneous for almond cultivars; sucrose was the main sugar (11.46 +/- 0.14 in
      Marcona to 22.23 +/- 0.59 in Ferragnes g/100 g of dried weight), followed by
      raffinose (0.71 +/- 0.05 in Ferraduel to 2.11 +/- 0.29 in Duro Italiano), glucose
      (0.42 +/- 0.12 in Pegarinhos two seeded to 1.47 +/- 0.19 in Ferragnes) and
      fructose (0.11 +/- 0.02 in Pegarinhos two seeded to 0.59 +/- 0.05 in Gloriette).
      Commercial cultivars proved to have higher sucrose contents, except in the case
      of Marcona. Nevertheless, chestnut cultivars revealed a high heterogeneity.
      Sucrose was the main sugar in Aveleira (22.05 +/- 1.48), Judia (23.30 +/- 0.83)
      and Longal (9.56 +/- 0.91), while glucose was slightly prevalent in Boa Ventura
      (6.63 +/- 0.49). The observed variance could serve for inter-cultivar
      discrimination.

PMID- 20033299
TI  - Biophysical mechanisms of single-cell interactions with microtopographical cues.
AB  - Biophysical cues encoded in the extracellular matrix (ECM) are increasingly being
      explored to control cell behavior in tissue engineering applications. Recently,
      we showed that cell adhesion to microtopographical structures ("micropegs") can
      suppress proliferation in a manner that may be blunted by inhibiting cellular
      contractility, suggesting that this effect is related to altered cell-scaffold
      mechanotransduction. We now directly investigate this possibility at the
      microscale through a combination of live-cell imaging, single-cell mechanics
      methods, and analysis of gene expression. Using time-lapse imaging, we show that
      when cells break adhesive contacts with micropegs, they form F-actin-filled
      tethers that extend and then rupture at a maximum, critical length that is
      greater than trailing-edge tethers observed on topographically flat substrates.
      This critical tether length depends on myosin activation, with inhibition of Rho
      associated kinase abolishing topography-dependent differences in tether length.
      Using cellular de-adhesion and atomic force microscopy indentation measurements,
      we show that the micropegs enhance cell-scaffold adhesive interactions without
      changing whole-cell elasticity. Moreover, micropeg adhesion increases expression
      of specific mechanotransductive genes, including RhoA GTPase and myosin heavy
      chain II, and, in myoblasts, the functional marker connexin 43. Together, our
      data support a model in which microtopographical cues alter the local mechanical
      microenvironment of cells by modulating adhesion and adhesion-dependent
      mechanotransductive signaling.

PMID- 20033300
TI  - Health status utilities and the impact of pressure ulcers in long-term care
      residents in Ontario.
AB  - PURPOSE: To estimate health status utilities in long-term care (LTC) residents in
      Ontario, both with and without pressure ulcers (PUs), and to determine the impact
      of PU on health-related quality of life (HRQOL). METHODS: A retrospective
      population-based study was carried out using Minimum Data Set (MDS) health
      assessment data among all residents in 89 LTC homes in Ontario who had a full MDS
      assessment between May 2004 and November 2007. The Minimum Data Set-Health Status
      Index (MDS-HSI) was used to measure HRQOL. A stepwise regression was used to
      determine the impact of PU on MDS-HSI scores. RESULTS: A total of 1,498 (9%) of
      16,531 LTC residents had at least one stage II PU or higher. The mean +/- SD MDS
      HSI scores of LTC residents without PU and those with PU were 0.36 +/- 0.17 and
      0.26 +/- 0.13, respectively (p < 0.001). Factors associated with lower MDS-HSI
      scores included: older age; being female; having a PU; recent hip fracture;
      multiple comorbid conditions; bedfast; incontinence; Changes in Health, End-stage
      disease and Symptoms and Signs; clinically important depression; treated with a
      turning/repositioning program; taking antipsychotic medications; and use of
      restraints. CONCLUSIONS: LTC residents with PU had slightly though statistically
      significantly lower HRQOL than those without PU. Comorbidity contributed
      substantially to the low HRQOL in these populations. Community-weighted MDS-HSI
      utilities for LTC residents are useful for cost-effectiveness analyses and help
      guide health policy development.

PMID- 20033301
TI  - Development of the olfactory bulbs in human fetuses (an immunohistochemical
      study).
AB  - An immunohistochemical study of the olfactory bulb (OB) in human fetuses was
      performed. Immunohistochemical markers for nervous system-specific protein
      complexes S-100 and SNAP-25 were used. At 20-22 weeks of development, the
      development of cells expressing protein S-100 was greater in the OB than in the
      neocortex (the areas of the gyrus rectus and the gyrus orbitalis longitudinalis
      internus). These quantitative differences indicate heterochronicity in glial
      differentiation in the OB and cerebral cortex. Immunopositive reactions for SNAP
      25 were for the first time detected at the periphery of the OB and in glomeruli
      in human fetuses at 15-16 and 20-22 weeks of development. Immunohistochemical
      staining of the OB with antibodies to SNAP-25 indicated that the human olfactory
      system cannot function prior to 20-22 weeks of development. In the OB of fetuses
      at 28-29 weeks of development, the intensity of the immunohistochemical reaction
      showed topological differences. The reaction with antibodies to SNAP-25 in the OB
      of full-term fetuses was similar to the reaction in the OB of adult humans. The
      results of these immunohistochemical studies using the reaction for the protein
      complex SNAP-25 in fetuses of different ages suggest the that the primary
      olfactory center in humans starts to function no earlier than the 30th week of
      development.

PMID- 20033302
TI  - Neurotransmitter composition of neurons in the cranial cervical and celiac
      sympathetic ganglia in postnatal ontogenesis.
AB  - The neurotransmitter composition of neurons in the cranial cervical ganglion
      (CCG) and celiac ganglia (CG) in rats of different ages (neonatal, 10, 12, 30,
      and 60 days) was studied by immunohistochemical methods. The results showed that
      most neurons in these sympathetic ganglia contain tyrosine hydroxylase (TH). Most
      TH-positive neurons were also neuropeptide Y (NPY)-positive. In all ganglia, the
      proportions of neurons containing NPY increased from the moment of birth to the
      end of the first month of life. In the CG, NPY was present in a significantly
      greater proportion of neurons than in the CCG. Substance P, vasoactive intestinal
      peptide, and choline acetyltransferase were present in occasional neurons in the
      CCG and CG from birth. There was no change in the proportion of this type of
      neuron with age. Definitive establishment of the neurotransmitter composition in
      the sympathetic ganglia studied here occurred by the end of the first month of
      life.

PMID- 20033303
TI  - Morphogenesis of the epidural space in humans during the embryonic and early
      fetal periods.
AB  - The development of the epidural space was studied on 51 series of sections from
      embryos and early fetuses aged from four to 13 weeks using histological and
      embryological methods for plastic and graphic reconstruction. We found that three
      stages can be discriminated in the development of the epidural space: I) the
      primary epidural space (embryos of 16-31 mm crown-rump length (CRL); II)
      reduction of the primary epidural space (embryos of 35-55 mm CRL); and III) the
      secondary epidural space (embryos of 60-70 mm CRL and fetuses of 80-90 mm CRL).
      The morphogenesis of the primary epidural space is determined by the formative
      influence of the spinal cord and its dura mater, while that of the secondary
      epidural space is determined by the walls of the vertebral canal. In the spinal
      cord-dura mater of the spinal cord-vertebral canal correlation system, the latter
      two components, subjected to the inducing influence of the first, determine the
      morphogenesis of the epidural space via a system of morphogenetic correlations.
      The correlational relationships are apparent as time-linked connections between
      the rudiment of the dura mater of the spinal cord and the vertebral canal,
      resulting in the stage-by-stage formation of the epidural space in the
      ventrodorsal and craniocaudal directions. These same morphogenetic correlations
      also determine the staging of the development of the epidural space.

PMID- 20033304
TI  - Monotherapy of epilepsy in women: psychiatric and neuroendocrine aspects.
AB  - The aim of the present work was to perform a comparative assessment of the
      efficacy and safety of traditional and contemporary antiepileptic agents in women
      of reproductive age. The experimental group consisted of 65 patients, of whom 48
      had partial epilepsy and 17 had idiopathic generalized epilepsy. A number of
      issues were addressed in studies of a larger group of patients (110), including
      both women (65) and men (45). The following agents were studied: Topamax,
      valproates, carbamazepine, and barbiturates, all used as monotherapy. Patients'
      status was evaluated using clinical (neurological, psychiatric), psychometric,
      neuropsychological, and hormonal parameters. The data led to the general
      conclusion that Topamax had advantages over the other study agents in the
      treatment of women with epilepsy.

PMID- 20033305
TI  - Use of memantine (akatinol) for the correction of cognitive impairments in
      Parkinson's disease complicated by dementia.
AB  - This study addresses the effects of 52 weeks of treatment with the NMDA glutamate
      receptor antagonist memantine on motor, cognitive, and mental disorders in
      patients with Parkinson's disease complicated by dementia, as compared with a
      control group of patients not treated with memantine. Patients of the
      experimental group (32 subjects) received memantine (20 mg/day), while patients
      in the control group continued on antiparkinsonism treatment alone. Cognitive,
      psychiatric, and motor symptoms were assessed before the study and then at the
      ends of weeks 12, 24, and 52, using clinical assessment, rating scales, and
      neuropsychological tests. Plasma homocysteine levels were measured by HPLC.
      Patients treated with memantine had better measures on the MMSE (p < 0.05), ADAS
      cog (p < 0.05), clock drawing test (p < 0.05), and FAB (p < 0.01) as compared
      with the control group by the end of study week 24. Members of the group of
      patients with high homocysteine levels mounted significantly better responses
      with memantine treatment, as compared with patients of the control group with
      high homocysteine levels but not receiving memantine, at the ends of study weeks
      24 and 52, in terms of all rating scales (UPDRS, MMSE, ADAS-cog, D-KEFS Verbal
      Fluency Test, FAB. NPI, and DAD, p < 0.05). By the end of week 52, significant
      changes in points scores on the NPI-12 scale from baseline were in favor of
      patients receiving memantine, this applying to the disinhibition (p = 0.006),
      irritability (p = 0.04), anxiety (p = 0.04), and hallucinations (p = 0.048)
      subscales. The presence of hyperhomocysteinemia may indicate faster progression
      of both motor and cognitive impairments in Parkinson's disease. Prolonged
      memantine treatment of patients with Parkinson's disease complicated by dementia
      leads to improvements in cognitive functions, stabilization of motor impairments,
      and decreases in the severity of mental disorders, especially in patients with
      hyperhomocysteinemia.

PMID- 20033306
TI  - Effects of gamma-aminobutyric acid on the Hering-Breuer inspiration-inhibiting
      reflex.
AB  - Acute experiments on rats were performed to study the effects of intraventricular
      microinjections of gamma-aminobutyric acid (GABA) on the volume-time parameters
      of external respiration and the inspiration-inhibiting Hering-Breuer reflex. The
      state of this reflex before and after GABA administration was assessed in terms
      of the extent of changes in the duration and amplitude of inspiratory
      oscillations in intrathoracic pressure in response to end-expiratory occlusion of
      the trachea. Administration of 20 microM GABA into the lateral ventricles of the
      brain decreased the minute ventilation (due to reductions in the respiratory
      frequency and respiratory volume), weakened respiratory muscle contractions, and
      decreased the peak airflow rate on inspiration and expiration. The response to
      end-expiratory occlusion decreased significantly after administration of GABA,
      demonstrating the involvement of GABAergic mechanisms in mediating the
      inspiration-inhibiting Hering-Breuer reflex.

PMID- 20033307
TI  - Experience in the use of the anticonvulsant pregabalin as an add-on therapy in
      patients with partial epilepsy with polymorphic seizures.

PMID- 20033308
TI  - Interrelationship between measures of pain reactions in inflammation and levels
      of depression in prenatally stressed rat pups.
AB  - The interrelationship between measures of pain reactions (number of flexion +
      shaking patterns) in the formalin test and the level of depression (duration of
      immobility) in the forced swimming (Porsolt) test was studied in prenatally
      stressed rat pups aged 7-8 days. Two series of experiments were performed, with
      different sequences of tests separated by intervals of one day. In the first
      series of experiments, the Porsolt test was performed first; in the second
      series, the formalin test was performed before forced swimming. The sequence of
      tests was found to have different effects on measures of pain and depression and
      their correlation in prenatally stressed and unstressed rat pups. The effects of
      the sequence of the depression test (before or after the formalin test) on
      measures of depression were different in prenatally unstressed and stressed rat
      pups. In the former there were no differences between the two test sequences,
      while in prenatally stressed rat pups the first sequence showed a significant
      increase in the duration of immobility. The order of testing had no effect on the
      pain response--there were no differences between the numbers of flexion + shaking
      patterns in either prenatally stressed rat pups or unstressed animals; measures
      of the pain response were significantly greater in the sequence in which the
      formalin test was followed by the Porsolt test in prenatally stressed individuals
      as compared with unstressed animals. A positive correlation between study
      parameters was seen in the first series in prenatally unstressed rat pups, while
      there was a negative correlation in prenatally stressed animals. In the second
      series, there were no significant relationships between measures. Thus, the
      sequelae of postnatal stress, as imposed by each test the day before the final
      test, were apparent only in prenatally stressed animals in terms of the level of
      depression.

PMID- 20033309
TI  - Involvement of extracellular superoxide dismutase in regulating brain blood flow.
AB  - The physiological role of extracellular superoxide dismutase (SOD3) has received
      insufficient study. We investigated the hypothesis that SOD3, which neutralizes
      superoxide anions (O2(-)) in the intercellular space of the brain, prevents the
      inactivation of nitric oxide (NO) and is thus involved in regulating cerebral
      vascular tone. Local brain blood flow was measured in the striatum of
      anesthetized rats during administration of various combinations of a SOD mimetic,
      a SOD inhibitor, an NO donor, and an NOS inhibitor into the striatum using a
      Hamilton syringe. In normal conditions, SOD3 was found to minimize O2(-) levels,
      protecting endogenously produced NO at a sufficient level to maintain cerebral
      vascular tone and reactivity. SOD3 was found to increase the vasodilatory effect
      of endogenously produced NO in the brain. SOD3 was found to neutralize superoxide
      anions produced in the brain during respiration of 100% O2 and to maintain basal
      NO levels and its vasodilatory potential in normobaric hyperoxia.

PMID- 20033310
TI  - Synchronization of EEG theta and alpha rhythms in an unconscious set to the
      perception of an emotional facial expression.
AB  - Coherence functions in cortical electrical potentials in the theta (4-7 Hz) and
      alpha ranges (8-13 Hz) recorded during the formation and testing stages of a
      visual set to facial images bearing an emotional expression (an angry face) were
      studied in healthy adult subjects (n = 35). Differences in the spatial
      synchronization between theta and alpha potentials were seen, especially in rigid
      forms of the set, in which cases of erroneous perception of facial expressions
      were seen with contrast and assimilative illusions. This group of subjects (n =
      23) showed increases in theta potentials between the dorsolateral areas of the
      frontal cortex (the orbitofrontal cortex) and the temporal area in the right
      hemisphere. A mechanism is proposed for the development of visual illusions.
      Analysis of the coherence functions of cortical potentials in the theta and alpha
      ranges generates a "window" which can be used to study the operation of the two
      functional systems integrating brain activity, i.e., the corticohippocampal and
      frontothalamic, in the perception of a facial expression. The frontothalamic
      system is associated with more diffuse types of cortical activation, especially
      in its anterior areas. The theta rhythm system evidently facilitates integration
      of the frontal cortex with the temporal area in the right hemisphere and the
      connections of the latter with the parietal and central zones in both
      hemispheres.

PMID- 20033311
TI  - The counting function and its representation in the parietal cortex in humans and
      animals.
AB  - Current data provide evidence that the ability to assess numbers is present not
      only in adult humans, but also in animals and children of preverbal age. Studies
      of behavior in infants and animals have demonstrated that the perception of
      number, the discrimination of quantities, and elementary addition and subtraction
      appear during onto- and phylogenesis before the appearance of speech. Number
      perception in humans and animals has common features: the greater the difference
      between numbers, the easier they are to discriminate; for a given difference
      between numbers, increases in size lead to increased difficulty in
      discrimination. Clinical data on counting impairments in patients and functional
      tomography studies of number operations in healthy subjects have shown that the
      key structures involved in number perception in humans are located in the
      parietal cortex. As demonstrated by experiments on monkeys and dogs, recognition
      of number in these species is also associated with the parietal area of the
      cortex. The similarity of the morphofunctional bases of "counting behavior" in
      humans and animals suggests that counting can be regarded as a functional
      mechanism of adaptive behavior which formed during evolution.

PMID- 20033312
TI  - Selective impairments to memory consolidation in chicks produced by 5'-iodo-2'
      deoxyuridine.
AB  - The aim of the present work was to study the role of DNA synthesis in the
      formation of different types of memory in neonatal chicks. The nucleotide analogs
      5'-iodo-2'-deoxyuridine (IdU) and 5'-bromo-2'-deoxyuridine (BrdU) were used;
      these are incorporated into DNA, impairing its function, and have amnestic
      actions in defined models of learning in mice. We studied the effects of 5'-iodo
      2'-deoxyuridine of the formation of long-term memory in chicks during training in
      different models: passive avoidance, imprinting, taste aversion, and spatial
      learning in a maze. In the taste aversion model, i.p. administration of IdU (10
      mg/kg 5 min before or 50 min after training) had an amnestic effect on testing 1
      2 days after training. IdU-induced amnesia developed more than 6 h after
      training, while administration of IdU 2 h after training had no amnestic effect.
      5'-Bromo-2'-deoxyuridine also had a similar amnestic action in the taste aversion
      model. In the passive avoidance, imprinting, and spatial maze learning models,
      administration of IdU at the same dose before and after training did not induce
      amnesia. These data lead to the suggestion that DNA synthesis in the brain may
      play a critical role in the mechanisms of memory consolidation in chicks in types
      of learning such as taste aversion.

PMID- 20033313
TI  - Evoked potentials in the rabbit visual cortex reflect changes in line orientation
      and intensity.
AB  - Changes in the amplitudes of evoked potentials in the visual cortex of conscious
      rabbits in response to substitution of flashing lines of different orientations
      (0-90 degrees ) but constant intensity were studied, along with interneurons of
      different intensities but constant orientation, and complex stimuli with
      simultaneous changes in flash orientation and intensity. Factor analysis of the
      results showed that analysis of the N85 peak of evoked potentials produced by
      substitution of stimuli with different orientations but constant intensity
      identified a two-dimensional sensory space for orientations. An achromatic
      sensory space was also detected using substitution of lines of different
      intensities but constant orientation. Substitution of complex stimuli involved
      two versions of the experiment. In the first version, four stimuli in the initial
      orientations (0-38.58 degrees ) had an intensity of 5 cd/m(2), the other stimuli
      (with orientations of 51.44-90 degrees ) were presented at an intensity of 15
      cd/m(2). On the plane of the sensory space formed by the first two significant
      factors, stimuli with different intensities were located in different quadrants
      of the circle, while within the quadrants themselves, the stimuli were located in
      accord with their orientations, from lower values to greater. It is suggested
      that in this version, an interaction between orientation and intensity attributes
      was seen on the single plane of the sensory space, with a clear predominance of
      the intensity factor. The other experimental version also included eight complex
      stimuli, each complex having its own orientation (one of eight over the range 0
      90 degrees ) and intensity (also one of eight, in the range 5-21 cd/m(2)). In all
      experiments involving substitution of complex stimuli, factor analysis identified
      three to four significant factors. In the vast majority of cases, only the
      sensory space plane X1, X2 was found, this being formed by two significant
      factors. On this plane, the stimuli were located in order of changes in
      intensity. This may be associated with the fact that rabbits are crepuscular
      animals, such that stimulus brightness is the most important attribute. However,
      in some cases, potentials in the rabbit brain also demonstrated simultaneous
      processing of two visual stimulus attributes, i.e., intensity and orientation.
      This may be evidence indicating analysis of complex stimuli in the primary visual
      cortex.

PMID- 20033314
TI  - Ontogenetic characteristics of behavior in rats subjected to hypoxia on day 14 or
      day 18 of embryogenesis.
AB  - Physiological development, motor activity, and cognitive functions were studied
      in rats subjected to acute normobaric hypoxic hypoxia (3 h at an O2 concentration
      of 7%) at different stages of embryogenesis (days E14 or E18). Prenatal hypoxia
      was found to lead to delays in physiological development and the establishment of
      motor behavior during the first month of postnatal ontogenesis. These changes
      were more marked in rats subjected to hypoxia on day 14 of intrauterine
      development and disappeared with age. In adult rats, regardless of the timing of
      exposure to hypoxia (E14 or E18), learning ability was degraded and long-term and
      short-term memory were impaired. These results suggest that exposure to the
      pathogenic factor during the main period of neuroblast generation and migration
      (E14) was significant both for physiological development and the establishment of
      motor behavior in the animals and for the execution of the cognitive functions of
      the brain, while exposure during the period at which maturation and
      differentiation processes dominate in the brain (E18) was more significant in
      relation to the execution of cognitive functions.

PMID- 20033315
TI  - Characteristics of the performance of a formed motor skill by rats with different
      motor preferences.
AB  - Wistar rats with different motor preferences were used to study performance of a
      food-procuring skill--extracting food from a narrow horizontal feeder tube. These
      experiments showed that when the preferred limb was used, left-handed rats
      performed the task more quickly (including both preliminary movements and the
      final successful movements) than right-handed rats. Comparison of movement
      performance times with the preferred and non-preferred limbs showed that the task
      was performed more quickly using the left paw in both left- and right-handed
      rats, i.e., independently of whether this was the preferred paw or not. At the
      final stage of task performance (grasping and extracting the food), the preferred
      paw was more successful than the non-preferred paw in both right- and left-handed
      animals. It is suggested that the organization of the overall strategy for
      performing this complex behavioral task in rats is determined by the functional
      heterogeneity of the right and left hemispheres of the brain, which is not linked
      with limb preference. The selected preference is based on the specific motor and
      precision characteristics of the preferred paw, while the contralateral
      hemisphere--the left in right-handed animals and the right in left-handed animals
      -has a special role in mediating these abilities.

PMID- 20033316
TI  - Ultrastructure of hippocampal field CA1 in rats after status epilepticus induced
      by systemic administration of kainic acid.
AB  - The ultrastructure of hippocampal field CA1 in rats was studied 14 days after
      status epilepticus induced by administration of kainic acid. Structural changes
      were seen in 40% of cells, predominantly interneurons, which showed both
      reversible changes (mitochondria with an electron-dense matrix or small numbers
      of short cristae, moderate dilation of rough endoplasmic reticulum (RER)
      cisterns, and small numbers of ribosomes) and more significant abnormalities:
      swollen mitochondria with very small numbers of cristae, which were partially
      degraded, some with damaged mitochondrial membranes, along with pathologically
      damaged RER components and focal or peripheral chromatolysis. Chromatolyzed areas
      sometimes contained membrane-like includes and vacuoles. In addition, the
      neuropil contained occasional large osmiophilic formations surrounded by
      astrocyte processes with accumulations of glycogen or gliofibrils.
      Synaptoarchitectonics were also altered. Asymmetrical synapses were often seen on
      small dendrites and spines, with highly osmiophilic postsynaptic zones, their
      synaptic terminals containing numerous synaptic vesicles and large vesicles with
      electron-dense cores. Some presynaptic endings showed clear signs of classical
      dark-type degeneration. As the nucleus remained intact in all types of altered
      neurons, it appears that most cells underwent pathological changes of the
      necrotic type.

PMID- 20033317
TI  - Changes in cell proliferation in the subventricular zone of the brain in adult
      rats given beta-amyloid peptide (25-35).
AB  - The effects of intracerebroventricular administration of fragment (25-35) of beta
      amyloid peptide [Abeta(25-35)] on cell proliferation in the subventricular zone
      of the dentate gyrus of the hippocampus in adult rats were analyzed. Animals
      received doses of 15 nmol of pre-aggregated Abeta(25-35) or the Abeta(35-25)
      control peptide, or solvent (sterile water) into the lateral ventricles. On post
      injection days 1-5, rats received intraperitoneal injections of the thymidine
      analog 5-bromo-2'-deoxyuridine (BrdU). BrdU incorporated into DNA was detected
      immunohistochemically on frontal brain sections six and 12 days after peptide
      administration. At six days, the numbers of BrdU-containing cells in the
      subventricular zone showed no differences between the study groups. At 12 days,
      the total number of BrdU-positive cells decreased significantly in all study
      groups. At the same time, the number of labeled cells in rats given Abeta(25-35)
      was significantly greater in this brain zone than in animals given water or the
      control peptide. Thus, Abeta(25-35) significantly increased cell proliferation in
      the subventricular zone after intracerebroventricular administration.

PMID- 20033319
TI  - Focused microwave thermotherapy for preoperative treatment of invasive breast
      cancer: a review of clinical studies.
AB  - BACKGROUND: Preoperative focused microwave thermotherapy (FMT) is a promising
      method for targeted treatment of breast cancer cells. Results of four multi
      institutional clinical studies of preoperative FMT for treating invasive
      carcinomas in the intact breast are reviewed. METHODS: Externally applied wide
      field adaptive phased-array FMT has been investigated both as a preoperative heat
      alone ablation treatment and as a combination treatment with preoperative
      anthracycline-based chemotherapy for breast tumors ranging in ultrasound-measured
      size from 0.8 to 7.8 cm. RESULTS: In phase I, eight of ten (80%) patients
      receiving a single low dose of FMT prior to receiving mastectomy had a partial
      tumor response quantified by either ultrasound measurements of tumor volume
      reduction or by pathologic cell kill. In phase II, the FMT thermal dose was
      increased to establish a threshold dose to induce 100% pathologic tumor cell kill
      for invasive carcinomas prior to breast-conserving surgery (BCS). In a randomized
      study for patients with early-stage invasive breast cancer, of those patients
      receiving preoperative FMT at ablative temperatures, 0 of 34 (0%) patients had
      positive tumor margins, whereas positive margins occurred in 4 of 41 (9.8%) of
      patients receiving BCS alone (P = 0.13). In a randomized study for patients with
      large tumors, based on ultrasound measurements the median tumor volume reduction
      was 88.4% (n = 14) for patients receiving FMT and neoadjuvant chemotherapy,
      compared with 58.8% (n = 10) reduction in the neoadjuvant chemotherapy-alone arm
      (P = 0.048). CONCLUSIONS: Wide-field adaptive phased-array FMT can be safely
      administered in a preoperative setting, and data from randomized studies suggest
      both a reduction in positive tumor margins as a heat-alone treatment for early
      stage breast cancer and a reduction in tumor volume when used in combination with
      anthracycline-based chemotherapy for patients with large breast cancer tumors.
      Larger randomized studies are required to verify these conclusions.

PMID- 20033318
TI  - Biochemical observations relating to oxidant stress injury in Chernobyl clean-up
      workers ("liquidators") from Latvia.
AB  - AIMS: To establish if there is further evidence for the long-term oxidant stress
      injury (as reported previously--Kumerova et al. in Biol Trace Elem Res 77:1-12,
      2000) in surviving Chernobyl nuclear power plant (NPP) workers from Latvia. The
      overall objectives of this study have been to establish if there have been long
      term systemic changes in the oxidant/antioxidant status of clean-up workers that
      might reflect adaptation to the progression of oxidative stress injury. METHODS:
      Biochemical analyses of the circulating levels of endogenous oxidants and anti
      oxidants were undertaken over two periods (Stage 1 in 1998-1999 and Stage 2 in
      2005-2006) at approximately 6-7 years time interval, in order to establish if
      there have been time-dependent changes in the parameters that may be important
      for the health of the clean-up workers. The biochemical analyses included (a)
      plasma levels of the anti-oxidant, selenium, (b) blood and plasma levels of
      glutathione peroxidase, (c) red blood cell catalase, (d) plasma total oxidant
      status as lipid peroxides and hydroperoxides, (e) plasma ceruloplasmin, and (f)
      total blood levels of zinc and copper. RESULTS: The circulating content of lipid
      peroxides, plasma oxidisability, lipid peroxides, catalase, Zn, and Cu were
      elevated above normal values at both the stages of this study. Glutathione
      peroxidase was increased above normal values at Stage 1 but not at Stage 2. The
      most pronounced changes between Stage 1 and Stage 2 were (a) a reduction by about
      (1/2) in the content of lipid peroxides and lipid peroxidation, but not in the
      blood oxidisability and (b) increased plasma selenium. The data show that there
      may be a partial improvement in the anti-oxidant/oxidant status of the Chernobyl
      NPP workers over the 7-year period of investigation. CONCLUSIONS: The NPP
      patients may be undergoing progressive reduction in blood oxidants accompanied by
      adaptation to oxidant stress injury due to the increased anti-oxidant activity
      measured in their plasma and blood.

PMID- 20033320
TI  - Intraoperative localization of insulinoma and normal pancreas using invisible
      near-infrared fluorescent light.
AB  - BACKGROUND: Neuroendocrine tumors of the pancreas, such as insulinoma, are
      difficult to localize, and complete resection is essential for cure. Our
      hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in
      insulinoma could provide high-sensitivity detection intraoperatively. MATERIALS
      AND METHODS: The optical properties of methylene blue (MB) were measured in vitro
      in 100% serum at 37 degrees C and in vivo after tissue uptake. MB was injected as
      a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype
      rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE imaging
      system was used to acquire color video and NIR fluorescence images simultaneously
      and in real-time. The signal-to-background ratios (SBR) of tissues and tumors
      were quantified using FLARE software. RESULTS: When appropriately diluted, MB
      exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses > or =1
      mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR
      fluorescent for up to 1 h with an SBR > or = 1.6. MB spectral properties are
      maintained after uptake into tissue. Interestingly, insulinoma exhibits even
      higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios
      of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity,
      real-time localization of primary, multicentric, and metastatic insulinoma and
      permitted differentiation among tumor, normal pancreas, and other abdominal
      structures. CONCLUSION: A single intravenous injection of a clinically available,
      commonly used NIR fluorophore provides prolonged intraoperative localization of
      normal pancreas and insulinoma using invisible NIR fluorescent light.

PMID- 20033321
TI  - Impact of the peritoneal surface disease severity score on survival in patients
      with colorectal cancer peritoneal carcinomatosis undergoing complete
      cytoreduction and hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: In patients with colorectal cancer peritoneal carcinomatosis (CRPC),
      only patients with a complete cytoreduction will benefit. The current selection
      criteria are ill-defined. The Peritoneal Surface Disease Severity (PSDS) staging
      was introduced as a basis of scoring patients into prognostic groups to improve
      patient selection. This study determines the impact on survival of the PSDS in a
      cohort of patients undergoing complete cytoreductive surgery (CRS) and
      hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPC. MATERIALS AND
      METHODS: A retrospective review of two prospective databases of patients with
      complete CRS and HIPEC for CRPC was performed to score patients on the PSDS.
      Survival was analyzed using the Kaplan-Meier method. Univariate and multivariate
      analyses were performed to determine the impact of various clinicopathological
      factors on survival. RESULTS: There were 56 patients who underwent complete
      cytoreduction and HIPEC. Of these, 6 patients (11%) were PSDS stage I and median
      survival (MS) has not been reached, 33 patients (59%) were PSDS stage II and MS
      was 38 months, 10 patients (18%) were PSDS stage III and MS was 24 months, and 7
      patients (13%) were PSDS stage IV and MS was 7 months. Univariate analysis
      demonstrated the association of clinical symptoms (P = .022), PSDS (P = .002),
      and tumor histopathology (P = .074) as factors affecting survival. Multivariate
      analysis demonstrated that PSDS (P = .002) was an independent positive predictive
      factor associated with survival. CONCLUSIONS: In patients with CRPC who undergo a
      complete cytoreduction and HIPEC, the PSDS staging system has been demonstrated
      to be an important prognostic indicator. It appears that even with a complete
      cytoreduction and HIPEC, patients with PSDS stage IV do not benefit from
      treatment.

PMID- 20033322
TI  - TGM2 is a novel marker for prognosis and therapeutic target in colorectal cancer.
AB  - BACKGROUND: Transglutaminase 2 (TGM2) plays a role in cell growth and survival
      through the antiapoptosis signaling pathway. METHODS: We analyzed TGM2 gene
      expression in 91 paired cases of colorectal cancer (CRC) and noncancerous regions
      and seven CRC cell lines to demonstrate the importance of TGM2 expression for the
      prediction of prognosis of CRC. TGM2 expression was higher in CRC tissue than in
      corresponding normal tissue by real-time reverse transcriptase-polymerase chain
      reaction (P = .015). RESULTS: Patients in the high TGM2 expression group showed a
      poorer overall survival rate than those in the low expression group (P = .001),
      indicating that the increase in TGM2 expression was an independent prognostic
      factor. TGM2 was also expressed in the seven CRC cell lines. The in vitro
      proliferation assay showed that TGM2 expression is involved with tumor growth.
      CONCLUSIONS: The present study suggests that TGM2 is useful as a predictive
      marker for patient prognosis and may be a novel therapeutic target for CRC.

PMID- 20033323
TI  - Rate of freeze alters the immunologic response after cryoablation of breast
      cancer.
AB  - BACKGROUND: Cryoablation has garnered significant interest as a treatment for
      solid tumors including breast cancer for both its local effects and potential in
      stimulating an antitumor immune response. We sought to examine the impact that
      variances in technique might have on the immune response and examine the
      mechanism by which cryoablation may stimulate an antitumor immune response.
      MATERIALS AND METHODS: Balb/c mice with established 4T1 mammary carcinomas were
      treated by cryoablation at either a high rate of freeze or low rate of freeze, or
      by surgical excision, after spontaneous metastases occurred. Tumor-draining lymph
      nodes (TDLN) were excised at 1 week for EliSPOT assay and immunophenotyping. Mice
      were followed after treatment for enumeration of pulmonary metastases and
      survival. RESULTS: Compared with surgical excision, cryoablation using a high
      freeze rate resulted in a significant increase in tumor-specific T cells in the
      TDLN, a reduction in pulmonary metastases, and improved survival. However,
      cryoablation using a low freeze rate resulted in an increase in regulatory T
      cells, a significant increase in pulmonary metastases, and decreased survival.
      CONCLUSIONS: Cryoablation of breast cancer in mice can generate a tumor-specific
      immune response that can eradicate systemic micrometastases and improve outcome
      compared with surgical excision; however, the technique used to freeze the tissue
      may alter the immune response from stimulatory to suppressive.

PMID- 20033324
TI  - Comparing the clinical and economic impact of laparoscopic versus open liver
      resection.
AB  - BACKGROUND: Laparoscopic liver resection has thus far not gained widespread
      acceptance among liver surgeons. Valid questions remain regarding the relative
      clinical superiority of the laparoscopic approach as well as whether laparoscopic
      hepatectomy carries any economic benefit compared with open liver surgery.
      OBJECTIVE: The aim of this work is to compare the clinical and economic impact of
      laparoscopic versus open left lateral sectionectomy (LLS). METHODS: Between May
      2002 and July 2008, 44 laparoscopic LLS and 29 open LLS were included in the
      analysis. Deviation-based cost modeling (DBCM) was utilized to compare the
      combined clinical and economic impact of the open and laparoscopic approaches.
      RESULTS: The laparoscopic approach compared favorably with the open approach from
      both a clinical and economic standpoint. Not only was the median length of stay
      (LOS) shorter by 2 days in the laparoscopic group (3 versus 5 days, respectively,
      P = 0.001), but the laparoscopic cohort also benefited from a significant
      reduction in postoperative morbidity (P = 0.001). Because the groups differed
      significantly in age and ratio of benign to malignant disease, a subgroup
      analysis limited to patients with malignant disease was undertaken. The same
      reduction in LOS and postoperative morbidity was evident within the malignant
      subgroup undergoing laparoscopic LLS (P = 0.003). The economic impact of the
      laparoscopic approach was noteworthy, with the laparoscopic approach US$1,527
      2,939 more cost efficient per patient compared with the open technique.
      CONCLUSION: Our study seems not only to corroborate the safety and clinical
      benefit of the laparoscopic approach but also suggests a fiscally important cost
      advantage for the minimally invasive approach.

PMID- 20033325
TI  - Predictors of completion axillary lymph node dissection in patients with
      immunohistochemical metastases to the sentinel lymph node in breast cancer.
AB  - BACKGROUND: Axillary lymph node dissection (ALND) in patients with
      immunohistochemistry (IHC)-determined metastases to the sentinel lymph node (SLN)
      is controversial. The goal of this study was to examine factors associated with
      ALND in IHC-only patients. METHODS: Retrospective review of an institutional SLN
      database from July 1997 to July 2003 was performed. We compared sociodemographic,
      pathologic, and therapeutic variables between IHC-only patients who had SLN
      biopsy alone and those that had ALND. RESULTS: Our study group consisted of 171
      patients with IHC-only metastases to the SLN. Young age, estrogen receptor
      negative status, high Memorial Sloan-Kettering Cancer Center nomogram score, and
      chemotherapy were associated with ALND. Among patients who had ALND (n = 95), 18%
      had a positive non-SLN. Rates of systemic therapy were similar between those with
      and without positive non-SLNs at ALND. No axillary recurrences were observed in
      this series with a median follow-up of 6.4 years. The percentage of patients who
      were recurrence-free after 5 years was 97% (95% confidence interval, 92.1-98.6).
      CONCLUSIONS: On the basis of our findings and the lack of prospective randomized
      data, the practice of selectively limiting ALND to IHC-only patients thought to
      be at high risk and to patients for whom the identification of additional
      positive nodes may change systemic therapy recommendations seems to be a safe and
      reasonable approach.

PMID- 20033326
TI  - Complete necrosis after transarterial chemoembolization could predict prolonged
      survival in patients with recurrent intrahepatic hepatocellular carcinoma after
      curative resection.
AB  - BACKGROUND: We explored the predictors of response to transarterial
      chemoembolization (TACE) in patients with recurrent intrahepatic hepatocellular
      carcinoma (HCC) after hepatectomy and investigated the survival of these patients
      according to the response to TACE. METHODS: We analyzed data from 199 consecutive
      HCC patients who underwent curative liver resection and who later received repeat
      TACE for intrahepatic HCC recurrence. RESULTS: Of 199 patients, 139 (69.8%)
      achieved complete necrosis (CN) of HCC after repeated TACE (mean TACE session
      number, 1.3) and the other 60 (30.2%) (non-CN group) did not achieve CN. At
      hepatectomy, the CN group showed significantly smaller proportions of tumor
      capsular invasion, microvascular invasion, and pathologic tumor-node-metastasis
      stage III or IV HCCs. At first TACE, the CN group showed a significantly greater
      proportion of patients with time to recurrence > or = 1 year, Child-Pugh class A,
      serum alpha-fetoprotein (AFP) levels < 200 ng/mL, tumor size < 3 cm, solitary
      tumors, and nodular tumor types; portal vein invasion were less common than seen
      in the non-CN group. After multivariate analysis, tumor size < 3 cm and a single
      tumor at first TACE were independently related to attainment of CN after TACE.
      Median survival after first TACE was significantly longer in the CN group (48.9
      versus 17.0 months). In a Cox regression model, CN after TACE was an independent
      predictor of favorable survival outcome after first TACE. CONCLUSIONS: CN after
      repeat TACE for postresection intrahepatic recurrence was attained more commonly
      in patients with smaller tumor size and lower tumor number at first TACE and
      favored longer survival in recurrent patients.

PMID- 20033328
TI  - A parallel robot to assist vitreoretinal surgery.
AB  - PURPOSE: This paper describes the development and evaluation of a parallel
      prototype robot for vitreoretinal surgery where physiological hand tremor limits
      performance. METHODS: The manipulator was specifically designed to meet
      requirements such as size, precision, and sterilization; this has six-degree-of
      freedom parallel architecture and provides positioning accuracy with micrometer
      resolution within the eye. The manipulator is controlled by an operator with a
      "master manipulator" consisting of multiple joints. RESULTS: Results of the in
      vitro experiments revealed that when compared to the manual procedure, a higher
      stability and accuracy of tool positioning could be achieved using the prototype
      robot. CONCLUSIONS: This microsurgical system that we have developed has superior
      operability as compared to traditional manual procedure and has sufficient
      potential to be used clinically for vitreoretinal surgery.

PMID- 20033327
TI  - Non-target screening analysis of river water as compound-related base for
      monitoring measures.
AB  - BACKGROUND, AIM, AND SCOPE: Building up a comprehensive accurate monitoring
      program requires the knowledge on the contamination in principal, complemented by
      detailed information on individual contaminants. The selection of pollutants to
      be considered in monitoring actions is based dominantly on the information
      available about their environmental relevance (e.g., persistence, bioaccumulation
      potential, toxicological and ecotoxicological properties) and their occurrence
      within the affected environmental system. Therefore, this study focused on the
      identification of organic contaminants in selected German and European rivers to
      demonstrate the usefulness of a screening approach as complementary base for the
      compound selection process within monitoring activities. MATERIALS AND METHODS:
      Gas chromatography-mass spectrometry-based screening analyses were performed on
      five and six samples from German and European rivers, respectively.
      Identification of individual contaminants was based on the investigation of mass
      spectral and gas chromatographic properties compared with databases and reference
      materials. RESULTS: This study summarized the results of non-target screening
      analyses applied to river water samples and focused dominantly on, so far,
      unnoticed organic contaminants. Numerous compounds have been identified belonging
      to the groups of pharmaceuticals, technical additives, pesticides, personal care
      products, and oxygen-, nitrogen-, and sulfur-containing compounds of obviously
      anthropogenic origin. They are discussed in terms of their structural properties,
      their possible application or usage, and the environmental information available
      so far. DISCUSSION: Generally, two different groups of compounds have been
      differentiated that might contribute to potential monitoring programs. Firstly,
      more specific contaminants characterizing the individual riverine systems have
      been depicted (e.g., 4-chloro-2-(trifluoromethyl)aniline, di-iso-propylurea). The
      consideration of these substances in monitoring analyses to be applied to the
      corresponding catchment areas is recommended in order to monitor the real state
      of pollution. Secondly, contaminants have been introduced that appeared with
      higher multiplicity throughout the different river systems (e.g., TMDD, TXIB).
      Since these compounds tend to obviously have an elevated environmental stability
      accompanied by a widespread distribution, it is recommended to consider them in
      international high-scale monitoring programs. CONCLUSIONS: For monitoring
      purposes, a fundamental knowledge on the diversity of pollutants is an important
      precondition, which can be supported by screening analyses. Obviously, numerous
      organic contaminants have been neglected so far in environmental studies on river
      water, comprising also investigation on potential harmful effects and, therefore,
      their implementation in monitoring activities has been hindered. RECOMMENDATIONS
      AND PERSPECTIVES: Therefore, based on the results of this study, screening
      analyses should be established as principle tools to improve and complement the
      substance spectra for monitoring purposes. Secondly, scientific efforts should be
      strengthened to expand our knowledge on actually appearing organic contaminants
      in riverine systems.

PMID- 20033329
TI  - First clinical experience in applying XperGuide in embolization of jugular
      paragangliomas by direct intratumoral puncture.
AB  - PURPOSE: The purpose of this study is to introduce a novel image-guided technique
      utilized in the embolization of jugular paraganglioma tumors, using preoperative
      diagnostic scans and planning together with perioperative X-ray fluoroscopy in a
      combined image. METHODS: A lesion center and a skin entry point on the patient
      are selected and connected with a straight line, which resembles the most ideal
      lesion access trajectory to be followed during the needle insertion. The skin
      entry point and the corresponding line location are selected such that it avoids
      the impenetrable bones and vital anatomical structures. Two viewing incidence
      angles are defined to guide the cranial needle insertion: the entry view tangent
      to the planned trajectory, and the progression view perpendicular to the path.
      RESULTS: The proposed method was applied in two patients with jugular
      paragangliomas in order to navigate needles to the lesion location and
      subsequently embolize the tumors. The perioperative registration took less than 8
      s. Using this method, it was possible to guide the needle within 5 mm of the
      planned path. CONCLUSION: The fluoroscopic needle navigation, overlaid on the
      corresponding soft tissue of the underlying anatomy, combined with a planned
      path, has been shown to be an accurate and efficient tool for needle guidance.
      The patient pose varied between the preoperative data and the fluoroscopy guided
      intervention, but this did not hinder the procedure.

PMID- 20033330
TI  - Robust calculation of the midsagittal plane in CT scans using the Kullback
      Leibler's measure.
AB  - OBJECTIVE: The identification of the interhemispheric fissure (IF) is important
      in clinical applications for brain landmark identification, registration,
      symmetry assessment, and pathology detection. The IF is usually approximated by
      the midsagittal plane (MSP) separating the brain into two hemispheres. We present
      a fast accurate, automatic, and robust algorithm for finding the MSP for CT scans
      acquired in emergency room (ER) with a large slice thickness, high partial volume
      effect, and substantial head tilt. MATERIALS AND METHODS: An earlier algorithm
      for MSP identification from MRI using the Kullback-Leibler's measure was extended
      for CT by estimating patient's head orientation using model fitting, image
      processing, and atlas-based techniques. The new algorithm was validated on 208
      clinical scans acquired mainly in the ER with slice thickness ranging from 1.5 to
      6 mm and severe head tilt. RESULTS: The algorithm worked robustly for all 208
      cases. An angular discrepancy (degrees) and maximum distance (mm) between the
      calculated MSP and ground truth have the mean value (SD) 0.0258 degrees (0.9541
      degrees) and 0.1472 (0.7373) mm, respectively. In average, the algorithm takes 10
      s to process of a typical CT case. CONCLUSION: The proposed algorithm is robust
      to head rotation, and correctly identifies the MSP for a standard clinical CT
      scan with a large slice thickness. It has been applied in our several CT stroke
      CAD systems.

PMID- 20033331
TI  - Towards real time 2D to 3D registration for ultrasound-guided endoscopic and
      laparoscopic procedures.
AB  - PURPOSE: A method to register endoscopic and laparoscopic ultrasound (US) images
      in real time with pre-operative computed tomography (CT) data sets has been
      developed with the goal of improving diagnosis, biopsy guidance, and surgical
      interventions in the abdomen. METHODS: The technique, which has the potential to
      operate in real time, is based on a new phase correlation technique: LEPART,
      which specifies the location of a plane in the CT data which best corresponds to
      the US image. Validation of the method was carried out using an US phantom with
      cyst regions and with retrospective analysis of data sets from animal model
      experiments. RESULTS: The phantom validation study shows that local translation
      displacements can be recovered for each US frame with a root mean squared error
      of 1.56 +/- 0.78 mm in less than 5 sec, using non-optimized algorithm
      implementations. CONCLUSION: A new method for multimodality (preoperative CT and
      intraoperative US endoscopic images) registration to guide endoscopic
      interventions was developed and found to be efficient using clinically realistic
      datasets. The algorithm is inherently capable of being implemented in a parallel
      computing system so that full real time operation appears likely.

PMID- 20033332
TI  - An intersubject variable regional anesthesia simulator with a virtual patient
      architecture.
AB  - PURPOSE: The main purpose is to provide an intuitive VR-based training
      environment for regional anesthesia (RA). The research question is how to process
      subject-specific datasets, organize them in a meaningful way and how to perform
      the simulation for peripheral regions. METHODS: We propose a flexible virtual
      patient architecture and methods to process datasets. Image acquisition, image
      processing (especially segmentation), interactive nerve modeling and permutations
      (nerve instantiation) are described in detail. The simulation of electric impulse
      stimulation and according responses are essential for the training of peripheral
      RA and solved by an approach based on the electric distance. RESULTS: We have
      created an XML-based virtual patient database with several subjects. Prototypes
      of the simulation are implemented and run on multimodal VR hardware (e.g.,
      stereoscopic display and haptic device). A first user pilot study has confirmed
      our approach. CONCLUSION: The virtual patient architecture enables support for
      arbitrary scenarios on different subjects. This concept can also be used for
      other simulators. In future work, we plan to extend the simulation and conduct
      further evaluations in order to provide a tool for routine training for RA.

PMID- 20033333
TI  - A prototype percutaneous transhepatic cholangiography training simulator with
      real-time breathing motion.
AB  - PURPOSE: We present here a simulator for interventional radiology focusing on
      percutaneous transhepatic cholangiography (PTC). This procedure consists of
      inserting a needle into the biliary tree using fluoroscopy for guidance. METHODS:
      The requirements of the simulator have been driven by a task analysis. The three
      main components have been identified: the respiration, the real-time X-ray
      display (fluoroscopy) and the haptic rendering (sense of touch). The framework
      for modelling the respiratory motion is based on kinematics laws and on the
      Chainmail algorithm. The fluoroscopic simulation is performed on the graphic card
      and makes use of the Beer-Lambert law to compute the X-ray attenuation. Finally,
      the haptic rendering is integrated to the virtual environment and takes into
      account the soft-tissue reaction force feedback and maintenance of the initial
      direction of the needle during the insertion. RESULTS: Five training scenarios
      have been created using patient-specific data. Each of these provides the user
      with variable breathing behaviour, fluoroscopic display tuneable to any device
      parameters and needle force feedback. CONCLUSIONS: A detailed task analysis has
      been used to design and build the PTC simulator described in this paper. The
      simulator includes real-time respiratory motion with two independent parameters
      (rib kinematics and diaphragm action), on-line fluoroscopy implemented on the
      Graphics Processing Unit and haptic feedback to feel the soft-tissue behaviour of
      the organs during the needle insertion.

PMID- 20033334
TI  - An improved finite element model for craniofacial surgery simulation.
AB  - PURPOSE: A novel approach is proposed for simulating the deformation of the
      facial soft tissues in the craniofacial surgery simulation. METHODS: A nonlinear
      finite mixed-element model (NFM-EM) based on solid-shell elements and Lagrange
      principle of virtual work is proposed, which addresses the heterogeneity in
      geometry and material properties found in the soft tissues of the face. Moreover,
      after the investigation of the strain-potential models, the biomechanical
      characteristics of skin, muscles and fat are modeled with the most suitable
      material properties. In addition, an improved contact algorithm is used to
      compute the boundary conditions of the soft tissue model. RESULTS: The
      quantitative validation and the comparative results with other models proved the
      effectiveness of the approach on the simulation of complex soft tissues. The
      average absolute value of errors stays below 0.5 mm and the 95% percentiles of
      the distance map is less than 1.5 mm. CONCLUSIONS: NFM-EM promotes the accuracy
      and effectiveness of the soft tissue deformation, and the effective contact
      algorithm bridges the bone-related planning and the prediction of the target
      face.

PMID- 20033335
TI  - Real-time Seldinger technique simulation in complex vascular models.
AB  - PURPOSE: Commercial interventional radiology vascular simulators emulate
      instrument navigation and device deployment, though none supports the Seldinger
      technique, which provides initial access to the vascular tree. This paper
      presents a novel virtual environment for teaching this core skill. METHODS: Our
      simulator combines two haptic devices: vessel puncture with a virtual needle and
      catheter and guidewire manipulation. The simulation software displays the
      instrument interactions with the vessels. Instruments are modelled using a mass
      spring approximation, while efficient collision detection and collision response
      allow real time interactions. RESULTS: Experienced interventional radiologists
      evaluated the haptic components of our simulator as realistic and accurate. The
      vessel puncture haptic device proposes a first prototype to simulate the
      Seldinger technique. Our simulator presents realistic instrument behaviour when
      compared to real instruments in a vascular phantom. CONCLUSION: This paper
      presents the first simulator to train the Seldinger technique. The preliminary
      results confirm its utility for interventional radiology training.

PMID- 20033336
TI  - Real-time endovascular guidewire position simulation using shortest path
      algorithms.
AB  - PURPOSE: Treatment of vascular disease often involves endovascular interventions
      which use the vascular system for delivering treatment devices via a previously
      inserted guidewire to the diseased site. Previous studies show relative
      reproducibility of guidewire position after insertion, indicating that the
      guidewire position is constrained and could be represented by an energy
      minimization approach. Such representation would support the surgeon's decision
      process in guidewire selection. METHODS: In this paper, we determine the
      guidewire position using a k-level graph based on 3D vessel information.
      Guidewire properties are incorporated into the graph as edge weights given by the
      local bending energy related to the local bending angle. The optimal path through
      this weighted directed graph is determined using a shortest path algorithm.
      Volumetric data of two different internal carotid artery phantoms (O 3.5-4.6 mm)
      was acquired. Two guidewires (O 0.33 mm) of different material properties
      (stainless steel, plastic-coated steel core) were inserted into the phantoms.
      RESULTS: The average RMS distance between actual and simulated guidewire
      positions varies from 0.9 mm (plastic coated) to 1.3 mm (stainless steel); the
      computation time to determine the position was <2s. CONCLUSIONS: The results
      indicate that the proposed technique yields reproducible and accurate guidewire
      positions within a short, clinically relevant time frame. These calculated
      positions may be useful in facilitating neurovascular interventions.

PMID- 20033337
TI  - An integrated tool for automated visualization of subdural electrodes in epilepsy
      surgery evaluation.
AB  - PURPOSE: An automated tool embedded in image processing and visualization
      software should be developed to visualize subdural electrodes on the human
      cortical surface of the brain. METHODS: For accurate positioning of electrodes on
      the cortical surface, preoperative magnetic resonance imaging (MRI) and
      postoperative computed tomography (CT) datasets of pharmacoresistant epilepsy
      patients were co-registered and segmented. For the brain segmentation of
      preoperative MRI a new algorithm was implemented. To account for the radial
      electrode displacement due to cortical deformation, a radial replacement function
      was developed. The automated tool was evaluated using intraoperative photographs
      and using a bimodal phantom. RESULTS: The tool visualizes electrodes fully
      automated in 1-5 min. The mismatch between calculated and reference electrode
      position derived from intraoperative photographs was <or=9 mm, and was based upon
      phantom data <or=1.6 mm. CONCLUSIONS: Empirical investigations have to be made to
      quantify the magnitude and the nature of transverse electrode displacement in
      order to investigate the practicability and to determine the accuracy of the
      developed tool. Depending on investigation results, a half-automated
      intraoperative photography based method might be an option to minimize electrode
      shift.

PMID- 20033338
TI  - Significance of limited hiatal dissection in surgery for achalasia.
AB  - INTRODUCTION: It is speculated that postoperative pathologic gastroesophageal
      reflux after Heller's myotomy can be diminished if the lateral and posterior
      phrenoesophageal attachments are left intact. The aim of this study was to
      evaluate the effectiveness of limited hiatal dissection in patients operated due
      to achalasia. METHODS: Prospective, randomized, 3 years follow-up of 84 patients
      operated due to achalasia. In 26 patients, Heller-Dor with complete hiatal
      dissection was done (G1), limited hiatal dissection combined with myotomy and
      Dor's procedure was performed in 36 patients (G2), and with Heller's myotomy
      alone in 22 (G3). Stationary manometry and 24 h pH study were performed in
      regular postoperative intervals. RESULTS: Postoperatively, higher median values
      of lower esophageal sphincter resting pressures were marked in G2 and G3, while
      patients in G1 were presented with higher median values of pH acid score (p <
      0.001). Abnormal DeMeester score 3 years after surgery was present in 23.1% of
      patients in G1 and 8.5% and 9.1% in G2 and G3 accordingly. There was no
      statistical difference between the groups concerning postoperative dysphagia
      recurrence. CONCLUSION: Indicating further long-term studies, 3 years after the
      operation limited hiatal dissection compared to complete obtains better reflux
      control in achalasia patients, regardless of Dor's fundoplication.

PMID- 20033339
TI  - Surgical outcomes and prognostic factors for T2 gallbladder cancer following
      surgical resection.
AB  - BACKGROUND: Depth of tumor invasion is an important prognostic factor for
      gallbladder cancer. The aim of this study was to investigate the
      clinicopathological prognostic factors of T2 gallbladder cancer. METHODS: We
      retrospectively reviewed the clinicopathological data and survival for 83
      patients with T2 gallbladder cancers who underwent surgical resection between
      January 1995 and December 2007. RESULTS: The overall survival rates were 48.9% at
      3 years and 29.3% at 5 years. Univariate analysis revealed that R0 resection (P <
      0.001), extended surgery (P = 0.028), lymph node dissection (P = 0.024), non
      infiltrative tumors (P = 0.001), well differentiation (P = 0.001), absence of
      lymphatic (P = 0.025), perineural (P = 0.001), and vascular (P = 0.025) invasion,
      absence of lymph node metastasis (P = 0.001), negative resection margin (P =
      0.016), and stage (P = 0.002) were significantly better predictors for survival.
      A significant difference in survival between Rx and R1 was not found. R0
      resection, lymph node dissection, well differentiation, and absence of perineural
      and vascular invasion were significantly independent prognostic factors for
      overall survival. Recurrence occurred in 48 patients (57.8%). Age older than 65
      years, R0 resection, non-infiltrative tumors, and good differentiation were
      significant independent predictors of disease-free survival by multivariate
      analysis. CONCLUSIONS: For T2 tumors, radical surgery including lymph node
      dissection should be performed to achieve R0 resection. Tumors with infiltrative
      types and suspicious lymph node metastasis in the intraoperative findings were
      candidates for aggressive surgical management to improve patient survival.

PMID- 20033340
TI  - Clinicopathologic features of gastric carcinoma with signet ring cell histology.
AB  - BACKGROUND: Reports of clinicopathological features and prognosis in patients
      with signet ring cell carcinoma of the stomach (SRC) are conflicting. The aim was
      to describe the clinicopathological features and prognosis of patients with SRC
      in comparison with non-signet ring cell carcinoma of the stomach (NSRC). METHODS:
      In this retrospective study, we reviewed the records of 1,439 consecutive
      patients diagnosed with gastric carcinoma who were resected surgically from 1993
      to 2003. Among them, 218 patients (15.1%) with SRC were compared with 1,221
      patients with NSRC. RESULTS: There were significant differences in tumor size,
      tumor location, macroscopic type, depth on invasion, lymph node metastasis,
      lymphatic invasion, tumor stage, chemotherapy, and curability between the
      patients with SRC histology and NSRC. The overall 5-year survival of patients
      with SRC was 44.9% as compared with 36.0% for patients with NSRC (P = 0.013).
      Multivariate analysis showed that lymph node metastasis and curative resection
      were significant factors affecting survival. A significant survival benefit for
      curative resection was observed, with a 5-year survival rate of 58.5% compared
      with non-curatively resected cases (8.4%). CONCLUSIONS: When stage matched, SRC
      patients had a similar survival to NSRC patients. Curative resection is
      recommended to improve the prognosis of patients with SRC.

PMID- 20033341
TI  - Should we trust the results of multivariate analysis?

PMID- 20033343
TI  - Emergence of imatinib resistance associated with downregulation of c-kit
      expression in recurrent gastrointestinal stromal tumor (GIST): optimal timing of
      resection.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common
      gastrointestinal mesenchymal tumors. The activating mutation in the KIT (c-kit;
      CD117) proto-oncogene with subsequent tyrosine kinase activation plays a central
      role in the pathogenesis of GIST. Tyrosine kinase inhibitors are an integral part
      of GIST therapy. Initial response to neoadjuvant imatinib can be expected in up
      to 70% of the patients, thus offering an opportunity to surgically treat those
      with locally advanced primary or recurrent GIST. This favorable response to
      imatinib, however, is plagued with development of secondary resistance during the
      course of therapy. CASE DESCRIPTION: We herein report a case of recurrent locally
      advanced GIST in an elderly man, with excellent performance status, successfully
      managed with the integration of neoadjuvant targeted therapy and surgery.
      DISCUSSION: Continued monitoring by a multidisciplinary team, including a
      surgeon, is vital for the success of neoadjuvant imatinib therapy for
      unresectable primary or recurrent GIST in the context of emergence of secondary
      resistance. As such, surgeons should participate in managing imatinib-treated
      GIST, as resection may become a viable curative option. This case also highlights
      that major oncologic resections can be safely performed in older persons when
      their performance status and comorbidities are carefully considered.

PMID- 20033342
TI  - Congenital anomalies of the gastrointestinal tract diagnosed in adulthood-
      diagnosis and management.
AB  - INTRODUCTION: Congenital anomalies of the gastrointestinal tract are a
      significant cause of morbidity in children and less frequently in adults. In rare
      cases, they may run undetected during childhood and may present during
      adolescence. These abnormalities include developmental obstructive defects of the
      duodenum and the small intestine, anomalies of rotation and fixation, intestinal
      duplications, and anomalies of the colon and rectum. DISCUSSION: When detected in
      adulthood, they may require different evaluation and surgical correction. Some of
      these anomalies should be managed surgically as soon as they cause symptoms.
      Others may cause persistent problems in adulthood requiring medical management
      for years. Herein, we present a comprehensive review of all the different ways of
      diagnosis and management of these anomalies reported in the literature.

PMID- 20033344
TI  - Long-term outcome after 92 duodenum-preserving pancreatic head resections for
      chronic pancreatitis: comparison of Beger and Frey procedures.
AB  - INTRODUCTION: Duodenum-preserving pancreatic head resection may be an alternative
      to pancreatoduodenectomy or drainage procedures for chronic pancreatitis. There
      are few studies directly comparing the long-term outcome after the operations
      described by Beger and Frey. METHODS: One hundred thirteen patients underwent
      duodenum-preserving pancreatic head resection for complications of chronic
      pancreatitis. Follow-up was obtained in 92 patients (42 Beger, 50 Frey, median
      follow-up almost 5 years). RESULTS: Overall/surgery-related perioperative
      morbidity was 30%/20% (Frey) and 40%/31% (Beger). In long-term follow-up (Frey vs
      Beger), 62% vs 50% were completely free of pain, but 6% vs 19% had pain at least
      once per week or daily, and 32% vs 31% experienced pain attacks at least once per
      year (n.s.). Diabetes mellitus occurred in 60% vs 57% (de novo 34% vs 17%). Rates
      of exocrine insufficiency were 76% vs. 74% (de novo 34% vs. 33%). Median gain in
      body weight was 2.5 vs 1.5 kg (n.s.), respectively. Four patients had clinically
      relevant biliary complications during follow-up requiring reintervention.
      CONCLUSIONS: Our (nonrandomized) comparison of the long-term outcome after Frey
      and Beger procedures for chronic pancreatitis reveals a tendency for better pain
      control with the Frey operation. The functional outcomes were almost identical.

PMID- 20033345
TI  - Myoglobinuria after laparoscopic radiofrequency ablation of liver tumors.
AB  - BACKGROUND: There are scant data in the literature about myoglobinuria after
      radiofrequency ablation (RFA) of liver tumors. The aim of this study is to
      analyze the incidence and identify the risk factors involved in this complication
      after RFA. PATIENTS AND METHODS: An initial case of myoglobinuria and acute
      kidney injury (AKI) during laparoscopic liver RFA after 10 years of the liver
      ablation program led to the design of this study. Prospective data were collected
      on 41 consecutive patients undergoing laparoscopic RFA at our institution over a
      9-month period. Urine myoglobin, serum creatinine kinase, and serum creatinine
      levels were obtained preablation and postablation. Variables were compared
      between patients to identify possible risk factors that might be related to this
      rare complication. Data are expressed as mean +/- standard error of the mean.
      RESULTS: Two patients were excluded from the study due to preoperative
      myoglobinuria of unknown etiology. Of the remaining 39 patients, three developed
      dark urine with significant myoglobinuria on postoperative day 1. Two of these
      patients had carcinoid liver metastases; the remaining patient had a metastatic
      colorectal lesion. The number of tumors ablated in these patients was 14, 11, and
      3 vs. 2.4 +/- 0.4 in the rest of the patients. Cumulative tumor volume was larger
      in the group of patients that developed the complication vs. those who did not
      (127.9 +/- 59.5 vs. 48 +/- 3 cm(3)). Two grounding pads were used in the three
      patients that had a complication vs. four pads in the rest of the patients. Dark
      urine was identified promptly intraoperatively and treated aggressively. All of
      these patients required intensive care unit (ICU) admission and had a prolonged
      hospital stay. Marked elevation of transaminases and creatinine kinase as well as
      a drop in hematocrit and platelet count was observed in patients with
      myoglobinuria. In our retrospective review of 706 patients that underwent liver
      RFA in the past 10 years, we detected 27 patients (3.8%) with ten or more lesions
      (11.9 +/- 0.4). None of these patients had significant elevation of serum
      creatinine postoperatively. In the whole series of 706 patients, 22 (3.2%) were
      found to have elevated creatinine after liver RFA, with return to baseline in all
      but seven patients in follow-up. CONCLUSION: Myoglobinuria after liver RFA is a
      rare but potentially devastating complication that may lead to AKI with
      significant morbidity and prolonged hospital stay. Patients with large tumor
      volumes requiring longer ablation times need to be monitored closely for the
      development of this complication. The fact that this was not observed in other
      patients with similar tumor characteristics suggests that individual patient
      related factors might play an important role.

PMID- 20033347
TI  - An unusual complication 4 years after laparoscopic adjustable banding: jejunal
      obstruction due to the connecting tube.
AB  - Laparoscopic adjustable gastric banding (LAGB) is an often performed bariatric
      procedure for morbid obesity. Several complications are known, including surgery
      and port-side-associated complications. As rare but serious late complication of
      LAGB, we describe a 50-year-old patient with periodic incomplete intestinal
      constriction due to the silicone connecting tube, 4 years after laparoscopic
      adjustable gastric banding was performed. Abdominal CT scan showed an obstructive
      ileus due to a loop in the connecting tube. After surgical removal of the
      connecting tube, the patient recovered without sequelae.

PMID- 20033346
TI  - Colonic gene expression in conventional and germ-free mice with a focus on the
      butyrate receptor GPR109A and the butyrate transporter SLC5A8.
AB  - INTRODUCTION: Butyrate is a bacterial fermentation product that produces its
      beneficial effects on colon through GPR109A, a butyrate receptor, and SLC5A8, a
      butyrate transporter. In this study, we compared the expression of GPR109A and
      SLC5A8 between conventional mice and germ-free mice to test the hypothesis that
      the expression of these two proteins will be decreased in germ-free mice compared
      to conventional mice because of the absence of bacterial fermentation products
      and that colonization of germ-free mouse colon with conventional bacteria will
      reverse these changes. METHODS: RNA was prepared from the ileum and colon of
      conventional mice and germ-free mice and used for RT-PCR to determine mRNA
      levels. Tissue sections were used for immunohistochemical analysis to monitor the
      expression of GPR109A and SLC5A8 at the protein level. cDNA microarray was used
      to determine the differential expression of the genes in the colon between
      conventional mice and germ-free mice. RESULTS: In conventional mice with normal
      bacterial colonization of the intestinal tract, GPR109A and SLC5A8 are expressed
      on the apical membrane of epithelial cells lining the ileum and colon. In germ
      free mice, the expression of GPR109A and SLC5A8 is reduced markedly in the ileum
      and colon. The expression returns to normal levels when the intestinal tract of
      germ-free mice is colonized with bacteria. The expression of the Na(+)-coupled
      glucose transporter, SGLT1, follows a similar pattern. Microarray analysis
      identifies approximately 700 genes whose expression is altered more than twofold
      in germ-free mice compared to conventional mice. Among these genes are the
      chloride/bicarbonate exchanger SLC26A3 and the water channel aquaporin 4. The
      expression of SLC26A3 and AQP4 in ileum and colon is reduced in germ-free mice,
      but the levels return to normal upon bacterial colonization. CONCLUSION: Gut
      bacteria play an active role in the control of gene expression in the host
      intestinal tract, promoting the expression of the genes that are obligatory for
      the biological actions of the bacterial fermentation product butyrate and also
      the genes that are related to electrolyte and water absorption.

PMID- 20033348
TI  - SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese
      patients with severe hepatic steatosis.
AB  - BACKGROUND: Visceral adipose tissue is known to release greater amounts of
      adipokines and free fatty acids into the portal vein, being one of the most
      predictive factors of nonalcoholic fatty liver disease (NAFLD). Our study has the
      purpose to evaluate sirtuin 1 (SIRT1), adiponectin, Forkhead/winged helix
      (FOXO1), peroxisome proliferator-activated receptor (PPAR)gamma1-3, and
      PPARbeta/delta mRNA expression in morbidly obese patients in three different
      lipid depots: visceral (VAT), subcutaneous (SAT), and retroperitoneal (RAT).
      Recent studies suggest that SIRT1, a NAD(+)-dependent deacetylase, protects rats
      from NAFLD. METHODS: We divided the patients in two groups: those with slight or
      moderate steatosis (hepatic steatosis, HS) and other comprising individuals with
      severe steatosis associated or not with necroinflammation and fibrosis (severe
      hepatic steatosis, SHS). The adipose tissue depots were obtained during bariatric
      surgery. Total RNAs were extracted using TRIzol. The amount of genes of interest
      was determined by quantitative real-time polymerase chain reaction. RESULTS: When
      comparing the two groups of patients, a decrease in SIRT1 was observed in VAT of
      morbidly obese patients in SHS group (p = 0.006). The mRNA expression of the
      other genes showed no differences in VAT. No difference was found either in SAT
      or in RAT for all genes in the study. In addition, the homeostasis model
      assessment for insulin resistance (HOMA-IR) value was higher in SHS group
      compared to HS (p = 0.006). Also, our results show that the mRNA expression of
      SIRT1 and the value of HOMA-IR were positively correlated in VAT of SHS patients
      (r = 0.654; p = 0.048). CONCLUSIONS: Downregulation of SIRT1 mRNA expression in
      VAT of SHS could be possible impairing mitochondria biogenesis and fatty acid
      oxidation, promoting severe steatosis in obese patients. Our results provide a
      possible proof of SIRT1 protective potential in VAT against NAFLD in humans.

PMID- 20033349
TI  - Simultaneous gastric and colic laparoscopic adjustable gastric band migration.
      Complication of bariatric surgery.
AB  - Laparoscopic adjustable gastric banding (LAGB) is a minimally invasive treatment
      for morbid obesity, which has proved its safety, efficiency, and reversibility.
      Postoperative complications are rare and might be related with the reservoir,
      connecting tube, or with the band itself. The lack or unspecificity of clinical
      signs and symptoms makes the diagnosis of gastric band erosion difficult. The
      authors present the case of a 54-year-old female, submitted to laparoscopic
      adjustable gastric banding in April 2004 (BMI = 40 kg/m(2)). During the first
      year, she reduced her body mass index to 30 and remained stable thereafter. In
      August 2008, while investigating a moderate colicky abdominal pain, she was
      submitted to a colonoscopy that showed part of the band inside the transverse
      colon. Two exams were performed: the abdominal CT scan, which showed the
      connecting tube inside the transverse colon lumen and the lap band which was
      apparently well positioned around the stomach, and an upper digestive endoscopy
      that revealed band migration to the stomach lumen. The patient underwent
      laparoscopic band removal and closure of both stomach and colon walls, thus
      treating the fistula. LAGB erosion and migration is a late complication of this
      surgery that frequently needs surgical removal. LAGB migration to colon or
      stomach is described in literature isolated. Simultaneous erosion to stomach and
      colon lumen, with a gastrocolic fistula formation, has never been described
      before, making this case a unique one.

PMID- 20033350
TI  - Production of biodiesel via enzymatic ethanolysis of the sunflower and soybean
      oils: modeling.
AB  - Biodiesel has become attractive due to its environmental benefits compared with
      conventional diesel. Although the enzymatic synthesis of biodiesel requires low
      thermal energy, low conversions of enzymatic transesterification with ethanol
      (ethanolysis) of oils to produce biodiesel are reported as a result of
      deactivation of the enzyme depending on the reaction conditions. The synthesis of
      biodiesel via enzymatic ethanolysis of sunflower and soybean oils was
      investigated. Kinetic parameters for the overall reactions were fitted to
      experimental data available in the literature with the Ping Pong Bi-Bi mechanism
      including the inhibition effect of the ethanol on the activity of lipase Novozyme
      435. The model was applied to a batch reactor and the experimental conversions
      were successfully reproduced. The modeling of a semibatch reactor with continuous
      addition of ethanol was also performed and the results showed a reduction of
      roughly 3 h in the reaction time in comparison with the batch-wise operation.

PMID- 20033351
TI  - Nanoparticle inhalation impairs coronary microvascular reactivity via a local
      reactive oxygen species-dependent mechanism.
AB  - We have shown that nanoparticle inhalation impairs endothelium-dependent
      vasodilation in coronary arterioles. It is unknown whether local reactive oxygen
      species (ROS) contribute to this effect. Rats were exposed to TiO(2)
      nanoparticles via inhalation to produce a pulmonary deposition of 10 microg.
      Coronary arterioles were isolated from the left anterior descending artery
      distribution, and responses to acetylcholine, arachidonic acid, and U46619 were
      assessed. Contributions of nitric oxide synthase and prostaglandin were assessed
      via competitive inhibition with N(G)-Monomethyl-L-Arginine (L-NMMA) and
      indomethacin. Microvascular wall ROS were quantified via dihydroethidium (DHE)
      fluorescence. Coronary arterioles from rats exposed to nano-TiO(2) exhibited an
      attenuated vasodilator response to ACh, and this coincided with a 45% increase in
      DHE fluorescence. Coincubation with 2,2,6,6-tetramethylpiperidine-N-oxyl and
      catalase ameliorated impairments in ACh-induced vasodilation from nanoparticle
      exposed rats. Incubation with either L-NMMA or indomethacin significantly
      attenuated ACh-induced vasodilation in sham-control rats, but had no effect in
      rats exposed to nano-TiO(2). Arachidonic acid induced vasoconstriction in
      coronary arterioles from rats exposed to nano-TiO(2), but dilated arterioles from
      sham-control rats. These results suggest that nanoparticle exposure significantly
      impairs endothelium-dependent vasoreactivity in coronary arterioles, and this may
      be due in large part to increases in microvascular ROS. Furthermore, altered
      prostanoid formation may also contribute to this dysfunction. Such disturbances
      in coronary microvascular function may contribute to the cardiac events
      associated with exposure to particles in this size range.

PMID- 20033352
TI  - Comparison of the predictability of neurological outcome by serum procalcitonin
      and glial fibrillary acidic protein in postcardiac-arrest patients.
AB  - BACKGROUND: In past research, procalcitonin (PCT) and glial fibrillary acidic
      protein (GFAP) have been reported to be useful biomarkers in predicting
      neurological outcome after the return of spontaneous circulation (ROSC) following
      out-of-hospital cardiac arrest (CA), although they have only been studied
      separately. In this study, we compared the usefulness of PCT and GFAP in
      predicting neurological outcome. METHODS: This study was a retrospective, single
      center analysis, conducted in the intensive-care unit of a university hospital.
      Twenty-one sequential post-CA patients were included. Serum samples were
      collected from patients at 12 and 24 h after ROSC. Serum PCT and GFAP were
      measured and compared in patients with favorable and unfavorable neurological
      outcomes, evaluated at 6 months using the Glasgow-Pittsburgh Cerebral Performance
      Categories. RESULTS: Serum PCT was significantly higher at 12 and 24 h in
      patients with unfavorable outcomes (P = 0.004 and 0.002, respectively). Serum
      GFAP was not significantly higher at 12 and 24 h in patients with unfavorable
      outcomes (P = 0.118 and 0.079, respectively). The combination of PCT and GFAP
      showed high predictive value for unfavorable outcomes (86.7% sensitivity and 100%
      specificity at 12 h; 100% sensitivity and 83.3% specificity at 24 h). CONCLUSION:
      Serum PCT is a marker of unfavorable neurological outcome in post-CA patients,
      and is superior to serum GFAP in the early phase.

PMID- 20033353
TI  - Continuous selective intraarterial infusion of nimodipine for therapy of
      refractory cerebral vasospasm.
AB  - BACKGROUND: For endovascular treatment of vasospasm after aneurysmal subarachnoid
      hemorrhage (aSAH), an intraarterial treatment course with the calcium channel
      antagonist nimodipine infused for 30 min is proposed. As some patients still show
      ongoing vasospasm thereafter, we report on our experience with an extended time
      period of selective intraarterial nimodipine administration. METHODS: In nine
      patients with aSAH and refractory cerebral vasospasm, we left the catheter in
      place within the internal carotid artery after angiography. On the neurosurgical
      ICU, a continuous infusion of intraarterial nimodipine was commenced, combined
      with intraarterial heparin anticoagulation. Therapy was controlled with extended
      neuromonitoring techniques. RESULTS: Three patients died from refractory
      vasospasm and a fourth suffered lethal sepsis. Three patients survived in a good
      clinical condition, two of them without apparent neurologic deficit. The efficacy
      of intraarterial nimodipine was best verified with regional CBF monitoring. TCD
      failed to detect vasospasm in two patients and missed improvement in four. Brain
      tissue oxygenation increased in all patients, but was not indicative of vasospasm
      in one. CT perfusion reflected the treatment course adequately in the qualitative
      scans. CONCLUSION: Selective continuous intraarterial nimodipine treatment for
      refractory cerebral vasospasm after aSAH seems feasible and may add to the
      endovascular therapeutic options. Appropriate monitoring technology is essential
      for further investigation of this novel technique.

PMID- 20033355
TI  - fMRI data visualization with BrainBlend and Blender.
AB  - The visualization and exploration of neuroimaging data is important for the
      analysis of anatomical and functional magnetic resonance (MR) images and
      thresholded statistical parametric maps. While two-dimensional orthogonal views
      of neuroimaging data are used to display statistical analyses, real three
      dimensional (3d) depictions are helpful for showing the spatial distribution of a
      functional network, as well as its temporal evolution. However, viewers that are
      freely available on the internet offer only limited rendering capabilities and
      depictions of temporal changes of the blood oxygen level-dependent (BOLD)
      response. In this article, we present BrainBlend, a toolbox for the software
      package Statistical Parametric Mapping (SPM), that generates voxeldata files to
      be used with the open-source 3d-software "Blender". Our interface between SPM and
      Blender permits the use of any Analyze- and Nifti-file for the creation of images
      and animations of transparent volumetric objects. Different kinds of anatomical,
      functional and statistical data can be rendered as volumetric objects in order to
      convey an immediate understanding of the three-dimensional shape. Representations
      of functional networks can be animated using a time course extracted from the
      general linear model or the independent component analysis. Relative BOLD
      activations of functional MR-images can be calculated for a time-resolved
      depiction of hemodynamic changes. The resulting animation can be displayed along
      with its corresponding paradigm matrix and the presented stimuli. BrainBlend is
      particularly suitable for the visual exploration of interactions between
      functional networks, for time-resolved animations of BOLD changes and meets high
      demands on visual quality in images and animations.

PMID- 20033356
TI  - One-step preparation of a TA-cloning vector from a specially designed parent
      plasmid containing a dual lacZ gene system.
AB  - A high-yield method was developed for producing a TA-cloning vector suitable for
      blue/white colony selection from a unique parent plasmid containing a dual lacZ
      gene system through a one-step restriction enzyme digestion, which creates a
      single-base 3'-overhang. The dual lacZ gene system was realized by inserting an
      inner lacZ gene between two single-base 3'-overhangs, creating restriction enzyme
      sites within the reading-frame-adjusted outer lacZ gene sequence in the parent
      plasmid. The proposed method overcomes problems, such as the inefficient
      digestion frequently observed when generating a TA-cloning vector and the
      difficulty of purifying TA-cloning vectors from the digestion mixture, while
      maintaining the applicability of blue/white colony selection. Moreover, the use
      of TA-cloning vector prepared by the proposed method can provide the distinguish
      tool of transformants carrying the cloning product from those carrying
      contaminating parent plasmids, recircularized plasmids derived from incompletely
      digested parent plasmid fragments, or intra-molecularly ligated TA-cloning
      vectors derived from T-overhangs missing TA-cloning vectors (instability of the T
      overhangs is another important consideration when designing TA-cloning vectors)
      by making all colonies except those carrying the cloning product appear blue
      during blue/white colony selection.

PMID- 20033354
TI  - Prophylaxis for venous thrombo-embolism in neurocritical care: a critical
      appraisal.
AB  - Venous thrombo-embolism (VTE) is frequently encountered in critically ill
      neurological and neurosurgical patients admitted to intensive care units. This
      patient population includes those with brain neoplasm, intracranial hemorrhage,
      ischemic stroke, subarachnoid hemorrhage, pre- and post-operative patients
      undergoing neurosurgical procedures and those with traumatic brain injury, and
      acute spinal cord injury (SCI). There is a wide variability in clinical practice
      for thromboprophylaxis in these patients, in part due to paucity of data based on
      randomized clinical trials. Here, we review the current literature on the
      incidence of VTE in the critically ill neurological and neurosurgical patients as
      well as appraise available data to support particular practice paradigms for
      specific subsets of these patients. Data synthesis was conducted via search of
      Medline, Cochrane databases, and manual review of article bibliographies.
      Critically ill neurological and neurosurgical patients have higher susceptibility
      to VTE. Intermittent compression devices with or without anti-thrombotics is
      generally the method of choice for thromboprophylaxis. Low molecular weight
      heparin is the method of choice in certain patient subgroups such as those with
      SCI and ischemic stroke. Inferior vena cava filters may play a role in
      thromboprophylaxis in selected cases. Without clear guidelines that can be
      universally applied to this diverse group of patients, prophylaxis for VTE should
      be tailored to the individual patient with cautious assessment of benefits versus
      risks. There is a need for higher level evidence to guide VTE prophylaxis in
      certain subgroups of this patient population.

PMID- 20033357
TI  - Cloning, expression, purification, and characterization of a novel esterase from
      Lactobacillus plantarum.
AB  - Lactobacillus plantarum is an important lactic acid bacterium, usually found as
      natural inhabitant of food, such as fermented vegetables and meat products.
      However, little information about lactic acid bacteria, especially concerning L.
      plantarum, as a source of useful enzymes has been reported. The aim of this study
      was to clone, express in Escherichia coli, purify, and characterize an esterase
      from L. plantarum ATCC 8014. The esterase gene (1014 bp) was amplified and cloned
      in pET14b expression vector to express a His(6)-tagged protein in E. coli.
      Recombinant L. plantarum esterase was purified by Ni-NTA resin, presenting an
      apparent molecular mass of about 38 kDa. It presented highest activity at pH 6.0
      and 40 degrees C. Also, it presented preference for p-nitrophenyl butyrate, but
      hydrolyzed more efficiently p-nitrophenyl acetate. Besides, this study shows, for
      the first time, CD data about secondary structure of an esterase from L.
      plantarum.

PMID- 20033358
TI  - Sonographic Identification of the intracompartmental septum in de Quervain's
      disease.
AB  - BACKGROUND: The intracompartmental septum in the first extensor compartment in
      patients with de Quervain's disease has been associated with disease development
      and prognosis. However, with the exception of surgical exploration, there is no
      way of detecting the septum. QUESTIONS/PURPOSES: We evaluated the accuracy of
      sonography for identifying the intracompartmental septum in the first extensor
      compartment in patients with de Quervain's disease using surgical findings as the
      reference standard. PATIENTS AND METHODS: We performed surgical release of the
      first extensor compartment in 43 wrists of 40 patients who were unresponsive to
      nonoperative treatment. In each case, a sonographic evaluation was performed
      before surgery by a radiologist and the sonographic and surgical findings were
      compared. RESULTS: Sonography identified the intracompartmental septum in 19 of
      the 19 septum-present wrists and absence of the septum in 23 of the 24 septum
      absent wrists. The sensitivity of sonography was 100% (95% confidence interval,
      80%-100%), its specificity 96% (95% confidence interval, 78%-100%), accuracy 98%
      (95% confidence interval, 87%-100%), positive predictive value 95% (95%
      confidence interval, 74%-100%), and negative predictive value 100% (95%
      confidence interval, 83%-100%). Sonography also identified septum-like structures
      in 15 of 37 (41%) asymptomatic contralateral wrists. CONCLUSIONS: Sonography is
      useful for detecting the intracompartmental septum in the first extensor
      compartment in patients with de Quervain's disease. LEVEL OF EVIDENCE: Level I,
      diagnostic study. See Guidelines for Authors for a complete description of levels
      of evidence.

PMID- 20033359
TI  - Cemented distal femoral endoprostheses for musculoskeletal tumor: improved
      survival of modular versus custom implants.
AB  - BACKGROUND: Advocates of newer implant designs cite high rates of aseptic
      loosening and failure as reasons to abandon traditional cemented endoprosthetic
      reconstruction of the distal femur. QUESTIONS/PURPOSES: We asked whether newer,
      modular distal femoral components had improved survivorship compared with older,
      custom-casted designs. PATIENTS AND METHODS: We retrospectively reviewed 254
      patients who underwent distal femoral endoprosthetic reconstruction. We excluded
      two patients with cementless implants, 27 with expandable prostheses, and 39 who
      had a nontumor diagnosis. This left 186 patients: 101 with older custom implants
      and 85 with contemporary modular implants. The minimum followup was 1 month
      (mean, 96.0 months; range, 1-336 months). The tumor was classified as Stage
      IIA/IIB in 122 patients, Stage IA/IB or benign in 43, and Stage III or metastatic
      in 21. RESULTS: Kaplan-Meier analysis revealed overall 10-, 20-, and 25-year
      implant survival rates of 77%, 58%, and 50%, respectively, using revision of the
      stemmed components as an end point. The 85 modular components had a greater 15
      year survivorship than the 101 custom-designed implants: 93.7% versus 51.7%,
      respectively. Thirty-five stemmed components (18.8%) were revised for aseptic
      loosening in 22 patients, implant fatigue fracture in 10, infection in two, and
      local recurrence in one. CONCLUSIONS: Cemented modular rotating-hinge distal
      femoral endoprostheses demonstrated improved survivorship compared with custom
      casted implants during this three-decade experience. Patients with low-grade
      disease and long-term survivors of high-grade localized disease should expect at
      least one or more revision procedures in their lifetime. LEVEL OF EVIDENCE: Level
      IV, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 20033360
TI  - Electrophysiological characterization of the cerebellum in the arterially
      perfused hindbrain and upper body of the rat.
AB  - In the present study, a non-pulsatile arterially perfused hindbrain and upper
      body rat preparation is described which is an extension of the brainstem
      preparation reported by Potts et al., (Brain Res Bull 53(1):59-67), 1. The
      modified in situ preparation allows study of cerebellar function whilst
      preserving the integrity of many of its interconnections with the brainstem,
      upper spinal cord and the peripheral nervous system of the head and forelimbs.
      Evoked mossy fibre, climbing fibre and parallel fibre field potentials and EMG
      activity elicited in forelimb biceps muscle by interpositus stimulation provided
      evidence that both cerebellar inputs and outputs remain operational in this
      preparation. Similarly, the spontaneous and evoked single unit activity of
      Purkinje cells, putative Golgi cells, molecular interneurones and cerebellar
      nuclear neurones was similar to activity patterns reported in vivo. The
      advantages of the preparation include the ability to record, without the
      complications of anaesthesia, stabile single unit activity for extended periods
      (3 h or more), from regions of the rat cerebellum that are difficult to access in
      vivo. The preparation should therefore be a useful adjunct to in vitro and in
      vivo studies of neural circuits underlying cerebellar contributions to movement
      control and motor learning.

PMID- 20033361
TI  - Adaptive effects of the beta2-agonist clenbuterol on expression of beta2
      adrenoceptor mRNA in rat fast-twitch fiber-rich muscles.
AB  - Administration of the beta(2)-agonist clenbuterol has been shown to reduce the
      expression of beta(2)-adrenoceptor (AR) mRNA in fast-twitch fiber-rich (extensor
      digitorum longus, EDL) muscle without changing that in slow-twitch fiber-rich
      (soleus, SOL) muscle in rats. However, the regulatory mechanism for muscle fiber
      type-dependent down-regulation of the expression of beta(2)-AR mRNA induced by
      clenbuterol is still unclear. Therefore, mRNA expression of transcriptional and
      post-transcriptional regulatory factors for beta(2)-AR mRNA levels in fast-twitch
      fiber-rich (EDL and plantaris, PLA) and slow-twitch fiber-rich (SOL) muscles in
      clenbuterol-administered (1.0 mg/kg body weight/day for 10 days, subcutaneous)
      rats was studied by real-time reverse transcription-polymerase chain reaction.
      Administration of clenbuterol significantly reduced expression of beta(2)-AR mRNA
      in EDL and PLA muscles without changing that in SOL muscle. Administration of
      clenbuterol also significantly reduced the mRNA expression of transcriptional
      regulatory factor (glucocorticoid receptor) and mRNA stabilizing factor (Hu
      antigen R) in EDL and PLA muscles without changing those in SOL muscle. These
      results suggest that muscle fiber type-dependent effects of clenbuterol on
      expression of beta(2)-AR mRNA are closely related to the down-regulation of mRNA
      expression of transcriptional and post-transcriptional regulatory factors for
      beta(2)-AR mRNA levels.

PMID- 20033362
TI  - Buprenorphine modulates methamphetamine-induced dopamine dynamics in the rat
      caudate nucleus.
AB  - Methamphetamine (METH) abuse and addiction present a major problem in the United
      States and globally. Oxidative stress associated with exposure to METH mediates
      to the large extent METH-evoked neurotoxicity. While there are currently no
      medications approved for treating METH addiction, its pharmacology provides
      opportunities for potential pharmacotherapeutic adjuncts to behavioral therapy in
      the treatment of METH addiction. Opioid receptor agonists can modulate the
      activity of dopamine neurons and could, therefore, modify the pharmacodynamic
      effects of METH in the dopaminergic system. Efficacy of the adjunctive medication
      with buprenorphine has been demonstrated in the treatment of cocaine addiction
      extending beyond opiate addiction. We investigated the interactions of morphine
      (10 mg/kg) and buprenorphine (0.01 and 10 mg/kg) with METH (2 mg/kg) affecting
      striatal dopaminergic transmission. The extracellular concentration of dopamine
      (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined
      using brain microdialysis coupled with high performance liquid chromatography
      with electrochemical detection (HPLC-ED) in the caudate nucleus of adult, awake,
      male Sprague-Dawley rats. Compared to METH alone, extracellular DA release was
      prolonged for 140 min without changes in DA peak-effect by combined treatment
      with morphine/METH. Morphine did not change DOPAC efflux evoked by METH. On the
      other hand, both buprenorphine doses attenuated the METH-induced DA peak-effect.
      However, whereas high buprenorphine dose extended DA outflow for 190 min, the low
      dose abbreviated DA release. High buprenorphine dose also shortened METH-induced
      decrease in DOPAC efflux. Data confirm that opiates modulate dopaminergic
      neurotransmission evoked by METH. Alteration of dopaminergic response to METH
      challenge under buprenorphine may suggest effectiveness of buprenorphine
      treatment in METH addiction.

PMID- 20033363
TI  - Insulin-producing cells derived from stem/progenitor cells: therapeutic
      implications for diabetes mellitus.
AB  - One of the most common diseases of the pancreas is diabetes mellitus. The current
      treatment of exogenous insulin supply is not fully capable of achieving tight
      control of glucose regulation, leading to long-term complications. Hence, recent
      success in islet transplantation-based therapies for diabetes mellitus and the
      extreme shortage of pancreatic islets have motivated recent efforts to develop
      renewable sources of islet-replacement tissue. Of clinical interest, I review the
      recent progress on stem cell-based strategies for diabetes in view of
      regenerative medicine.

PMID- 20033364
TI  - Formation of secretory granules by chromogranins.
AB  - This review article covers the molecular mechanisms of secretory granule
      formation by chromogranin transfection. Recently, a few investigators have
      reported that the transfection of chromogranin A and B produces the structures of
      secretory granules. We used the GFP-chromogranin A transfection method to
      nonendocrine cells, COS-7 cells, which are not equipped with secretory granules.
      Despite the absence of endogenous secretory granules in nontransfected COS-7
      cells, COS-7 cells transfected with chromogranin A contained granule-like
      structures in electron micrographs. The granules were composed of an outer
      limiting membrane with core structures that were interpreted as secretory
      granules. Human chromogranin A (CgA) labeled with 5-nm gold particles was present
      in several dense-core granules in our previous electron microscopy study. This
      review depicts the role of chromogranin A in the formation of secretory granules.
      It emphasizes the application of recently developed new technologies and the
      genesis of secretory granules.

PMID- 20033365
TI  - Expression and localization of tricellulin in human nasal epithelial cells in
      vivo and in vitro.
AB  - Tricellulin was identified as the first marker of the tricellular tight junction,
      which forms at the meeting points of three cells, and it is required for the
      maintenance of the transepithelial barrier. Although it is also considered to be
      important for the mucosal barrier of the upper respiratory tract, little is known
      about its expression and localization. In the present study, we examined the
      expression and localization of tricellulin in normal human nasal epithelial cells
      in vivo and in vitro, especially using primary cultures and telomerase reverse
      transcriptase (hTERT)-transfected cells. In human nasal epithelial cells in vivo
      and in vitro, mRNA and protein of tricellulin were detected. It was localized not
      only at tricellular contacts but also at bicellular borders, and in part
      colocalized with occludin. In human nasal epithelium, by immunoelectron
      microscopy analysis, tricellulin-associated gold particles were observed around
      the junction-like structure of the uppermost region. By treatment with 10% fetal
      bovine serum (FBS), expression of tricellulin mRNA was weakly increased, whereas
      that of bicellular tight junction molecules was strongly increased, in real-time
      PCR. These results suggest that tricellulin is stably expressed in human nasal
      epithelial cells and may play an important role for the sealing of the corner at
      tricellular contacts to prevent infiltration by various inhaled viruses and
      antigens.

PMID- 20033366
TI  - Expression of claudin-4 and -7 in porcine gingival junctional epithelium.
AB  - Junctional epithelium, a nonkeratinized stratified epithelium, extends apically
      in apposition to the surface of the enamel to form a seal between the epithelium
      and the tooth. Desmosomes and gap junctions adhere to the junctional epithelium
      through cell-cell contact, but no evidence of tight junctions has been found.
      Recently, tight junction hallmark proteins and tight junction-related structures
      have been identified in stratified squamous epithelium. The present study
      examined whether tight junction proteins were expressed in the junctional
      epithelium. We used immunohistochemical techniques to observe expression of
      claudin-1, -4, -5, -7, and occludin in porcine gingival junctional epithelium.
      Claudin-4 exhibited immunoreactivity in the intercellular spaces of all layers of
      the oral epithelium and the junctional epithelium. Stronger expression was
      observed in junctional epithelial cells adjacent to the inner and outer basal
      laminae than in the inner cell layers. Immunohistochemical positivity for claudin
      7 was clearly observed in the junctional epithelium, but only a faint positivity
      was observed in the basal layer of the oral epithelium. No immunohistochemical
      positivity for claudin-1, -5, or occludin was observed in the junctional
      epithelium. RT-PCR assay confirmed expression of porcine claudin-4 and -7 mRNAs
      in the junctional epithelium. These findings indicate that claudin-4 and -7 may
      play a role in the junctional epithelium even in the absence of tight junctions.

PMID- 20033367
TI  - Increased ovarian follicle atresia in obese Zucker rats is associated with
      enhanced expression of the forkhead transcription factor FOXO1.
AB  - It is well established that hyperinsulinemia, resulting from insulin resistance,
      plays a role in the pathophysiology of polycystic ovary syndrome (PCOS). The aim
      of this study was to investigate if ovarian follicular development and atresia
      are impaired in obese hyperinsulinemic (fa/fa) Zucker rats. To gain insight into
      the molecular mechanism of follicular atresia, we also examined the expression
      and localization of forkhead transcription factor FOXO1, a major regulator of
      cell fate decisions such as differentiation, cell-cycle arrest, and cell death.
      Serum insulin but not gonadotropin levels were significantly higher in obese
      (fa/fa) rats when compared to lean controls. Total ovarian follicle number and
      the percentage of atretic follicles were also significantly increased in obese
      (fa/fa) rats. Follicle atresia was associated with nuclear accumulation of FOXO1
      transcription factor in TUNEL-positive granulosa cells. These results suggest a
      role for FOXO1 in granulosa cell apoptosis and increased ovarian follicle atresia
      associated with hyperinsulinemia.

PMID- 20033368
TI  - Immunohistochemical analyses of E-cadherin, beta-catenin, CD44s, and CD44v6
      expressions, and Ki-67 labeling index in intraductal papillary mucinous neoplasms
      of the pancreas and associated invasive carcinomas.
AB  - We examined the expressions of adhesion molecules (E-cadherin, beta-catenin,
      CD44s, and CD44v6) and Ki-67 labeling index (Ki-67 LI) in low- and moderate-grade
      dysplasia and invasive carcinoma components in ten noninvasive intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas and eight invasive
      carcinomas associated with IPMNs of the pancreas using immunohistochemical
      methods. There was no significant difference in regard to the proportion of
      components expressing either E-cadherin or beta-catenin in more than 70% of the
      tumor cells between the low- and moderate-grade dysplasia components. In
      contrast, the proportion of those in invasive carcinoma components was
      significantly lower than in low- or moderate-grade dysplasia components. Also,
      there was no significant difference in the proportion of components expressing
      CD44s or CD44v6 in more than 5% of tumor cells among low-grade dysplasia,
      moderate-grade dysplasia, and invasive carcinoma components. In contrast, the Ki
      67 LI values increased in the order of low-grade dysplasia, moderate-grade
      dysplasia, and invasive carcinoma components, with significant differences among
      them. The present results indicate that carcinoma components are associated with
      a decrease in tumor cells expressing E-cadherin and beta-catenin and have the
      highest proliferative activity.

PMID- 20033369
TI  - Histopathology of the tubuli recti at the start of experimental autoimmune
      orchitis in mice.
AB  - We previously established an experimental model of autoimmune orchitis (EAO) by
      means of immunization with testicular germ cells (TGC) alone in mice and
      confirmed that the disease can be transferred to mice that had received CD4+ but
      not CD8+ or B lymphocytes obtained from TGC-immunized donor mice. The tubuli
      recti (TR) are special in that lymphocytes first accumulate around them before
      spreading to the peripheral seminiferous tubules in EAO. However, the minute
      changes in the TR remain unknown. Therefore, we investigated the histopathology
      of the TR before the induction of spermatogenic disturbance. The results revealed
      that the first infiltrating lymphocytes around the TR were not only of T-cell but
      also of B-cell lineage. Moreover, it was also shown that some of these
      infiltrating lymphocytes migrated into the TR, with resultant degeneration of the
      TR epithelium before damage to the seminiferous epithelium. These findings
      indicate that TR epithelial cells are the first targets of autoreactive T and B
      lymphocytes in EAO.

PMID- 20033370
TI  - Chronic sclerosing pyelitis with an increased number of IgG4-positive plasma
      cells.
AB  - IgG4-related disease has been recently described. This disease occurs in various
      anatomic locations including pancreas, biliary tract, liver, retroperitoneum,
      kidney, breast, lung, thyroid gland, prostate, salivary gland, lacrimal gland,
      and lymph node. In this article, we report the first case of IgG4-related disease
      arising in the renal pelvis. A 49-year-old Japanese woman was found to show left
      hydronephrosis by a medical checkup. Histological examination of the renal pelvic
      tumor showed IgG4-related disease. Her postoperative serum IgG4 was elevated, and
      this was compatible with IgG4-related disease. Systemic examination showed
      swelling of major and minor salivary glands and the lacrimal glands, and biopsy
      of the minor salivary gland revealed the finding of IgG4-related disease.
      Finally, pathologists and clinicians should be aware of the possibility that the
      renal pelvis may be involved in IgG4-related systemic disease.

PMID- 20033371
TI  - A case of solitary fibrous tumor of the kidney: an immunohistochemical and
      ultrastructural study with a review of the literature.
AB  - A solitary fibrous tumor (SFT) is an unusual spindle cell neoplasm that usually
      arises in the pleura but rarely occurs in the kidney. Despite its rarity,
      histological diagnosis of SFT is crucial to avoid misdiagnosis with other
      malignant tumors in the kidney. We report a SFT of the left kidney that presented
      as a malignant tumor on radiographic findings in a 75-year-old Japanese woman.
      The tumor was well circumscribed and composed of a mixture of spindle cells and
      dense collagenous bands with no areas of necrosis or cystic changes noted
      macroscopically or microscopically. Electron microscopy showed fibroblast-like
      cells with well-developed rough endoplasmic reticulum, surrounded with collagen
      fibers. Immunohistochemistry revealed reactivity for vimentin, CD34, Bcl-2, and
      CD99, but no staining for cytokeratin, S-100, desmin, actin, D2-40, or epithelial
      membrane antigen (EMA). These findings were compatible with those of SFT.
      Although SFT of the kidney is extremely rare, this tumor must be included in the
      differential diagnosis when we encounter renal tumors consisting of mesenchymal
      elements. Immunohistochemical study is the key to diagnosis for SFT, and
      ultrastructural study is useful for its diagnosis.

PMID- 20033372
TI  - Immunohistochemical and electron microscopic studies of a case of duodenal
      gangliocytic paraganglioma.
AB  - Gangliocytic paraganglioma (GPG) is a rare tumor, occurring almost exclusively in
      the duodenum. In the present case, a submucosal tumor 2.5 x 2 x 1.5 cm in size
      was located on the anal side of the papilla of Vater, with clear margins and
      without capsule on cut-surface examination. Tumor cells included three types of
      cells: ganglion-like cells (GCs), endocrine cells (ECs), and Schwann cells (SCs).
      The GCs were large with eccentric nuclei with large nucleoli and clear abundant
      cytoplasm. ECs were detected in small nests, surrounded by bundles of SCs.
      Immunohistochemically, GCs were positive for synaptophysin, neuron-specific
      enolase (NSE), and CD56. ECs were positive for chromogranin A, NSE, somatostatin,
      pancreatic polypeptide, and CD56, and were associated with S100 protein-positive
      SCs. On fine structural examination, ECs contained numerous membrane-bounded
      secretory granules, 250-450 nm in diameter, in their cytoplasm, surrounded by a
      branched, complex basal lamina. SCs possessed basal lamina along their long
      interlacing cytoplasmic processes. The histogenesis of GPG most likely involves
      proliferation and differentiation of pluripotent stem cells in the duodenal
      crypts in the duodenum as a true tumor, although it is also possible that the
      retroperitoneal components of both GCs and SCs proliferate, together with ECs,
      from ventral primordial tissue of the pancreas in the duodenum. The
      immunohistochemical and ultrastructural findings of a case of GPG are reported,
      focusing on three major cellular components: GCs, ECs, and SCs.

PMID- 20033374
TI  - Angiogenesis inhibition. Introduction.

PMID- 20033373
TI  - Application of immunocytochemistry to the diagnosis of primary epithelioid
      angiosarcoma of the lung.
AB  - Pulmonary epithelioid angiosarcoma is rare, and there are no descriptions of the
      immunocytochemistry of such a case. We report a case with focus on
      immunocytochemistry of imprint cytological specimens here. A 43-year-old Japanese
      man presented with cough. Brushing cytology of the tumor using a bronchoscope
      showed a malignant neoplasm. Subsequently, left lower lobectomy was undertaken.
      Imprint cytological material of the neoplastic cells noted some clusters of
      round, or oval, to polygonal epithelioid cells. Histological examination showed
      the proliferation of epithelioid neoplastic cells containing erythrocytes in the
      cytoplasm. The immunocytochemistry in imprint cytological specimens showed a
      focal positive reaction for von Willebrand factor, and the immunohistochemistry
      of the surgically resected lung tumor showed a focal positive reaction for Fli-1,
      von Willebrand factor, CD31, and CD34. Finally, we suggest that the
      immunocytochemical study of imprint cytological materials may supply available
      information in diagnosing angiosarcoma with epithelioid features lacking
      characteristic structures.

PMID- 20033375
TI  - Angiopoietins.
AB  - The formation of new blood vessels plays an important role during the development
      and progression of a disease. In recent years, there has been a tremendous effort
      to uncover the molecular mechanisms that drive blood vessel growth in adult
      tissues. Angiopoietins belong to a family of growth factors that are critically
      involved in blood vessel formation during developmental and pathological
      angiogenesis. The importance of Angiopoietin signaling has been recognized in
      transgenic mouse models as the genetic ablation of Ang-1, and its primary
      receptor Tie2 has led to early embryonic lethality. Interesting and unusual for a
      family of ligands, Ang-2 has been identified as an antagonist of Ang-1 in
      endothelial cells as evidenced by a similar embryonic phenotype when Ang-2 was
      overexpressed in transgenic mice. In this review, we focus on the functional
      consequences of autocrine Angiopoietin signaling in endothelial cells.

PMID- 20033376
TI  - HIF-1alpha and cancer therapy.
AB  - Most solid tumors develop regions of hypoxia as they grow and outstrip their
      blood supply. In order to survive in the stressful hypoxic environment, tumor
      cells have developed a coordinated set of responses orchestrating their
      adaptation to hypoxia. The outcomes of the cellular responses to hypoxia are
      aggressive disease, resistance to therapy, and decreased patient survival. A
      critical mediator of the hypoxic response is the transcription factor hypoxia
      inducible factor 1 (HIF-1) that upregulates expression of proteins that promote
      angiogenesis, anaerobic metabolism, and many other survival pathways. Regulation
      of HIF-1alpha, a component of the HIF-1 heterodimer, occurs at multiple levels
      including translation, degradation, and transcriptional activation, and serves as
      a testimony to the central role of HIF-1. Studies demonstrating the importance of
      HIF-1alpha expression for tumor survival have made HIF-1alpha an attractive
      target for cancer therapy. The growing l.ist of pharmacological inhibitors of HIF
      1 and their varied targets mirrors the complex molecular mechanisms controlling
      HIF-1. In this chapter, we summarize recent findings regarding the regulation of
      HIF-1alpha and the progress made in identifying new therapeutic agents that
      inhibit HIF-1alpha.

PMID- 20033377
TI  - Chemokines.
AB  - Tumor growth is restricted to approximately 2 microm diameters by simple
      dissociation of nutrients and oxygen. Hence, tumors require the formation of new
      blood vessels for further growth progression. This process is referred to as
      tumor neo-angiogenesis. The process of tumor neo-angiogenesis is directed by
      complex bidirectional interactions between the tumor and the vessels, and creates
      a favorable microenvironment for angiogenesis. The tumor vessel system not only
      facilitates tumor growth by providing nutrients and oxygen but also functions as
      a convenient route for metastasis. A group of small cytokine-like molecules
      called chemokines have been shown to participate in angiogenesis under
      homeostatic and neoplastic conditions. This review summarizes their role in tumor
      associated angiogenesis.

PMID- 20033378
TI  - Angiogenesis inhibition in cancer therapy: platelet-derived growth factor (PDGF)
      and vascular endothelial growth factor (VEGF) and their receptors: biological
      functions and role in malignancy.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen
      in vitro and an angiogenic inducer in a variety of in vivo models. VEGF gene
      transcription is induced in particular in hypoxic cells. In developmental
      angiogenesis, the role of VEGF is demonstrated by the finding that the loss of a
      single VEGF allele results in defective vascularization and early embryonic
      lethality. Substantial evidence also implicates VEGF as a mediator of
      pathological angiogenesis. In situ hybridization studies demonstrate expression
      of VEGF mRNA in the majority of human tumors. Platelet-derived growth factor
      (PDGF) is mainly believed to be an important mitogen for connective tissue, and
      also has important roles during embryonal development. Its overexpression has
      been linked to different types of malignancies. Thus, it is important to
      understand the physiology of VEGF and PDGF and their receptors as well as their
      roles in malignancies in order to develop antiangiogenic strategies for the
      treatment of malignant disease.

PMID- 20033379
TI  - Vascular integrins: therapeutic and imaging targets of tumor angiogenesis.
AB  - Cells, including endothelial cells, continuously sense their surrounding
      environment and rapidly adapt to changes in order to assure tissues and organs
      homeostasis. The extracellular matrix (ECM) provides a physical scaffold for cell
      positioning and represents an instructive interface allowing cells to communicate
      over short distances. Cell surface receptors of the integrin family emerged
      through evolution as essential mediators and integrators of ECM-dependent
      communication. In preclinical studies, pharmacological inhibition of vascular
      integrins suppressed angiogenesis and inhibited tumor progression.
      alpha(V)beta(3) and alpha(V)beta(5) were the first integrins targeted to suppress
      tumor angiogenesis. Subsequently, additional integrins, in particular
      alpha(1)beta(1), alpha(2)beta(1), alpha(5)beta(1), and alpha(6)beta(4), emerged
      as potential therapeutic targets. Integrin inhibitors are currently tested in
      clinical trials for their safety and antiangiogenic/antitumor activity. In this
      chapter, we review the role of integrins in angiogenesis and present recent
      advances in the use of integrin antagonists as potential therapeutics in cancer
      and discuss future perspectives.

PMID- 20033380
TI  - PDGF and vessel maturation.
AB  - Pericytes are smooth muscle-like cells found in close contact with the
      endothelium in capillaries, where they regulate the morphology and function of
      the vessels. During vessel formation, platelet-derived growth factor-BB (PDGF-BB)
      is required for the recruitment and differentiation of pericytes. Tumor vessels
      display abnormal morphology and increased endothelial proliferation, resulting in
      leaky, tortuous vessels that are often poorly perfused. These vessels typically
      display decreased pericyte density, and the tumor-associated pericytes often
      express abnormal markers and show abnormal morphology. Anti-angiogenic therapy
      targeting pro-angiogenic growth factor pathways has been applied to a broad range
      of solid tumors with varying results. Studies utilizing mouse models indicate
      that the presence of pericytes protect endothelial cells against inhibition of
      vascular endothelial growth factor (VEGF) signaling. Simultaneous inhibition of
      PDGF receptors on pericytes therefore improves the effect of VEGF inhibitors on
      endothelial cells and enhances anti-angiogenic therapy.

PMID- 20033381
TI  - Lymphangiogenesis in cancer: current perspectives.
AB  - Although the lymphatic system has been initially described in the sixteenth
      century, basic research has been limited. Despite its importance for the
      maintenance of tissue fluid homeostasis and for the afferent immune response,
      research of the molecular mechanisms of lymphatic vessel formation and function
      has for a long time been hampered. One reason could be because of the
      difficulties of visibility due to the lack of lymphatic markers. But since the
      discovery of several molecules specifically expressed in lymphatic endothelial
      cells, a rediscovery of the lymphatic vasculature has taken place. New scientific
      insights has facilitated detailed analysis of the nature and organization of the
      lymphatic system in physiological and pathophysiological conditions, such as in
      chronic inflammation and metastatic cancer spread. Knowledge about the molecules
      that control lymphangiogenesis and tumor-associated lymphangiogenesis is now
      expanding, allowing better opportunities for the development of drugs interfering
      with the relevant signaling pathways. Advances in our understanding of the
      mechanisms have translated into a number of novel therapeutic studies.

PMID- 20033382
TI  - Compounds in clinical Phase III and beyond.
AB  - Targeted therapies against cancer have become more and more important. In
      particular, the inhibition of tumor angiogenesis and vascular targeting have been
      the focus of new treatment strategies. Numerous new substances were developed as
      angiogenesis inhibitors and evaluated in clinical trials for safety, tolerance,
      and efficacy. With positive study results, some of these molecules have already
      been approved for clinical use. For example, this is true for the vascular
      endothelial growth factor neutralizing antibody bevacizumab (BEV) in metastatic
      colorectal cancer, nonsmall cell lung cancer, renal cancer, and breast cancer.
      The tyrosine kinase (TK) inhibitors sorafenib and sunitinib have been approved
      for metastatic renal cancer as well as for hepatocellular carcinoma, and
      sunitinib has also been approved for gastrointestinal stroma tumors. In this
      chapter we try to give an overview of the substances currently investigated in
      Phase III studies and beyond with regard to antiangiogenesis in cancer therapy.

PMID- 20033383
TI  - Metronomic chemotherapy: principles and lessons learned from applications in the
      treatment of metastatic prostate cancer.
AB  - By frequent and protracted administration of conventional cytotoxic drugs without
      prolonged interruptions, the primary treatment target shifts from the tumor cell
      population to the tumor vasculature. This "metronomic" way of chemotherapy
      administration results in antivascular effects, the mechanistic basis of which
      remains to be fully elucidated. We outline the basic aspects of the metronomic
      concept, describe the results of clinical applications of such chemotherapy by
      focusing on studies in metastatic prostate cancer, and discuss certain
      shortcomings. Based on preclinical findings, we finally point to the possible
      ways to address these shortcomings in order to bring this novel and promising use
      of conventional anticancer agents to full fruition.

PMID- 20033384
TI  - Targeting inflammatory cells to improve anti-VEGF therapies in oncology.
AB  - Vascular endothelial growth factor A (VEGF-A) is a well-characterized regulator
      of physiological and pathological angiogenesis. Multiple therapeutic compounds
      interfering with VEGF-A-regulated signal transduction pathways are currently
      being developed for the treatment of neoplasias and other malignancies associated
      with pathological angiogenesis. A major challenge in developing anti-VEGF
      therapies are tumor intrinsic refractoriness and the emergence of treatment
      induced resistance. A variety of molecular and cellular mechanisms contribute to
      tumor angiogenesis, including the recruitment of bone marrow (BM)-derived
      endothelial cell progenitors (EPCs) and inflammatory cells to the tumor mass.
      Among the latter, two types of tumor infiltrating, inflammatory cells were
      recently identified to mediate refractoriness to anti-VEGF treatment: CD11b +
      Gr1+ myeloid derived suppressor cells (MDSC) and tumor-associated macrophages
      (TAMs). In this chapter, we review some of the inflammatory components regulating
      tumor angiogenesis and their roles in mediating refractoriness toward anti-VEGF
      treatment. In addition, we discuss potential therapeutic strategies targeting
      angiogenic pathways regulated by inflammatory cells. A better understanding of
      the biological and molecular events involved in mediating refractoriness to anti
      VEGF treatment may help to further improve therapeutic strategies targeting tumor
      angiogenesis.

PMID- 20033385
TI  - Antibody-based vascular tumor targeting.
AB  - The inhibition of angiogenesis represents a major step toward a more selective
      and better-tolerated therapy of cancer. An alternative way to take advantage of a
      tumor's absolute dependence on a functional neovasculature is illustrated by the
      strategy of "antibody-based vascular tumor targeting." This technology aims at
      the selective delivery of bioactive molecules to the tumor site by their
      conjugation to a carrier antibody reactive with a tumor-associated vascular
      antigen. A number of high-affinity monoclonal antibodies are nowadays available
      which have demonstrated a remarkable ability to selectively localize to the tumor
      vasculature. Indeed, some of them have already progressed from preclinical animal
      experiments to clinical studies in patients with cancer, acting as vehicles for
      the site-specific pharmacodelivery of proinflammatory cytokines or
      radionuclides.In this chapter, we present a selection of well-characterized
      markers of angiogenesis which have proven to be suitable targets for antibody
      based vascular targeting approaches. Furthermore, different transcriptomic and
      proteomic methodologies for the discovery of novel vascular tumor markers are
      described. In the last two sections, we focus on the discussion of antibody-based
      vascular tumor targeting strategies for imaging and therapy applications in
      oncology.

PMID- 20033386
TI  - Caveolae and cancer.
AB  - All blood vessels are lined by a layer of endothelial cells that help to control
      vascular permeability. The luminal surface of vascular endothelial cells is
      studded with transport vesicles called caveolae that are directly in contact with
      the blood and can transport molecules into and across the endothelium. The
      vasculature within distinct tissue types expresses a unique array of proteins
      that can be used to target intravenously injected antibodies directly to that
      tissue. When the tissue-specific proteins are concentrated in caveolae, the
      antibodies can be rapidly pumped out of the blood and into the tissue. Tumors
      appear to be a distinct tissue type with their own unique marker proteins.
      Targeting accessible proteins at the surface of tumor vasculature with
      radiolabeled antibodies destroys tumors and drastically increases animal
      survival. One day, it may be possible to specifically pump targeted molecules
      into tumors. This could increase therapeutic efficacy and decrease side effects
      because most of the drug would accumulate specifically in the tumor. Thus,
      targeting caveolae may provide a universal portal to pump drugs, imaging agents,
      and gene vectors out of the blood and into underlying tissue.

PMID- 20033387
TI  - [Postoperative wound infections: essentials for the internal medicine].
AB  - Surgical site infections are the most common nosocomial infections in surgical
      wards. The main risk factor is the comorbidity of patients. In addition, there
      are many preoperative and intraoperative factors that increase the risk of
      surgical site infections. Appropriate antimicrobial prophylaxis, adequate
      preparation of the patients by cessation of smoking and reducing weight are
      likely to prevent postoperative infections outside the operating theatre. The WHO
      has issued guidelines to prevent not only infectious, but also non-infectious
      complications after surgery. Surveillance of surgical site infections itself with
      adequate feedback to the surgeons decreases the rate by approximately 30%.

PMID- 20033388
TI  - [Nephrogenic systemic fibrosis: a rare disease with grave consequences].
AB  - Nephrogenic systemic fibrosis (NSF) is a progressive, potentially fatal systemic
      multiorgan fibrosing disease related to exposure of patients with advanced renal
      failure to the gadolinium-based contrast agents (GBCAs) used in magnetic
      resonance imaging. Because of this relationship between nephrogenic systemic
      fibrosis and gadolinium-based contrast agents, the U.S. Food and Drug
      Administration currently warns against using gadolinium-based contrast agents in
      patients with a glomerular filtration rate less than 30 ml per minute per 1.73
      m(2), or any acute kidney injury related to the hepatorenal syndrome or
      perioperative liver transplantation. Linear non-ionic GBCAs that are more prone
      to release free gadolinium are the more likely to cause NSF. The mechanism for
      NSF is not fully understood, yet risk factors have been described. As there is no
      established therapy for NSF the prevention of exposure to gadolinium is crucial
      in high risk patients.

PMID- 20033389
TI  - [Scleroderma].
AB  - Scleroderma (synonyms: systemic sclerosis, systemic scleroderma) is a systemic
      disease which affects the skin as well as internal organs such as the lungs,
      gastrointestinal tract, kidneys, and the heart. Pathogenetically a distinction
      should be made between uncontrolled formation of extracellular matrix proteins
      (fibrosis) and vasculopathy. In addition to organ fibrosis, this leads to a
      clinical picture of vascular manifestations. These include fingertip ulcers,
      pulmonary arterial hypertension, and acute renal crisis. Localized forms of
      scleroderma, such as morphea, which do not involve organ complications, should be
      differentiated from systemic sclerosis. Due to its clinical heterogeneity and
      high rate of morbidity and mortality, systemic sclerosis poses an enormous
      diagnostic and therapeutic challenge in everyday clinical practice. This review
      article summarizes the current status of classification and epidemiology,
      pathogenesis, and the most important clinical manifestations such as interstitial
      fibrosis, pulmonary arterial hypertension, acute renal crisis, and peripheral
      vasculopathy and provides an overview of current and future treatment options.

PMID- 20033390
TI  - Fine mapping of pepper trichome locus 1 controlling trichome formation in
      Capsicum annuum L. CM334.
AB  - Trichomes are present on nearly all land plants and protect plants against insect
      herbivores, drought and UV radiation. The trichome-bearing phenotype is conferred
      by the dominant allele of the pepper trichome locus 1 (Ptl1) in Capsicum annuum,
      Mexican 'Criollo de Morelos-334' (CM334). A genetic analysis using simple
      sequence repeats from pepper cDNA identified the HpmsE031 marker as tightly
      linked to Ptl1 in 653 individuals of an F(2) population derived from a cross
      between CM334 and Chilsungcho varieties. A bacterial artificial chromosome (BAC)
      library from CM334 covering 12x of the genome was screened using the HpmsE031 SSR
      marker as a probe and three BAC clones were identified. The Ptl1 region was
      covered by one 80 kb BAC clone, TT1B7. Fluorescence in situ hybridization (FISH)
      confirmed that TT1B7 localized to pepper chromosome 10. One co-dominant marker,
      Tco, and one dominant marker, Tsca, were successfully developed from the TT1B7
      BAC sequence. Tco mapped 0.33 cM up from Ptl1 and Tsca mapped 0.75 cM down from
      Ptl1. Analysis of the BAC sequence predicts the presence of 14 open reading
      frames including 60S ribosomal protein L21-like protein (Solanum demissum),
      protein kinase 2 (Nicotiana tabacum), hypothetical proteins, and unnamed protein
      products. These results will provide not only useful information for map-based
      cloning of Ptl1 in Capsicum but also the starting points for analysis of R-gene
      cluster inked with Ptl1.

PMID- 20033391
TI  - Development of a novel Sinapis arvensis disomic addition line in Brassica napus
      containing the restorer gene for Nsa CMS and improved resistance to Sclerotinia
      sclerotiorum and pod shattering.
AB  - An allo-cytoplasmic male sterile line, which was developed through somatic
      hybridization between Brassica napus and Sinapis arvensis (thus designated as Nsa
      CMS line), possesses high potential for hybrid production of rapeseed. In order
      to select for restorer lines, fertile plants derived from the same somatic
      hybridization combination were self-pollinated and testcrossed with the parental
      Nsa CMS line for six generations. A novel disomic alien addition line, B. napus
      S. arvensis, has been successfully developed. GISH analysis showed that it
      contains one pair of chromosomes from S. arvensis and 19 pairs from B. napus, and
      retains stable and regular mitotic and meiotic processes. The addition line
      displays very strong restoration ability to Nsa CMS line, high resistance to
      Sclerotinia sclerotiorum and a low incidence of pod shattering. Because the
      addition line shares these very important agricultural characters, it is a
      valuable restorer to Nsa CMS line, and is named NR1 here (Nsa restorer no. 1).

PMID- 20033392
TI  - [Periprosthetic fractures of the knee joint].
AB  - The demographic developments and an increasing number of total knee replacements
      will lead to more periprosthetic fractures in the future. These fractures can be
      classified into intraoperative and postoperative. Revisions in particular are
      associated with a higher incidence of intra-operative fractures, specifically for
      the tibia and patella. Most fractures occur in the postoperative period with an
      average of 2-4 years after the primary procedure. Most commonly the femur is
      involved. The history and clinical examination as well as imaging are crucial for
      the treatment as loose components would significantly alter the treatment
      strategy. In this case a revision has to be carefully planned. In the majority of
      the cases the prosthesis is well fixed especially at the femur. An open reduction
      internal fixation (ORIF) can then be carried out. A stable situation must be
      achieved to provide early post-operative mobilization. Also an anatomic reduction
      should be achieved with correct alignment especially with respect to varus/valgus
      and rotation. Modern locked implants can provide this with good success also with
      the possibility of minimally invasive techniques and polyaxial screw positioning.
      Retrograde intramedullary devices can be a feasible alternative. Similar
      principles can be used for the tibia whereas the patella can be stabilized with
      tension band wiring in the case of good bone stock but still remains a problem in
      case of bad bone stock.

PMID- 20033393
TI  - [Current strategies of conservative and operative treatment of the most frequent
      muscular disorders].
AB  - Though up to now no causal treatment for the majority of neuromuscular disorders
      is available, their disease progress and above all the quality of life of these
      patients can be decisively improved by established medical procedures. The main
      symptom is variably rapid, progressive muscle weakness, which leads to muscular
      imbalance and differently manifested impairment of motor functions. This results
      in the essential orthopaedic problems in these patients, e.g. contractures and
      deformities of the lower and upper extremities, foot deformities and sitting
      instability due to progressive scoliosis. Since the affected muscles have no
      physiological adaptability, they cannot be trained like healthy muscles. The
      orthopaedic treatment includes conservative methods, e.g. physiotherapy, orthotic
      devices and aids as well as surgical spine stabilisation and correction of the
      contractures of the lower extremities. Very important in the care of patients
      with neuromuscular disorders are the early prophylaxis and treatment of
      respiratory insufficiency by regular respiratory therapy to learn breathing and
      coughing techniques and self-exercises as well as the timely initiation of
      assisted ventilation.

PMID- 20033394
TI  - [Botulinum toxin A in children with infantile cerebral palsy: indications and
      treatment concepts].
AB  - Botulinum toxin A treatment in children with cerebral palsy is now well
      established as a safe and effective therapy option. However, a standardised
      injection strategy is still lacking. There is no doubt concerning the necessity
      for long-term therapy to cover the duration of motor development as well as for
      adequate prevention of fixed contractures. The appropriate dose and treatment
      concept to be used, however, is still controversial. The modern BoNT-A treatment
      concept must combine safety and efficacy with the availability of this treatment
      option throughout the duration of growth in these children. Consequently, in
      order to provide the best possible support for motor development at each
      individual motor milestone and using moderate dose recommendations, the "Key
      Muscle Concept" has been developed.

PMID- 20033395
TI  - [Neuro-orthopaedics].

PMID- 20033397
TI  - Prehension synergies and control with referent hand configurations.
AB  - We used the framework of the equilibrium-point hypothesis (in its updated form
      based on the notion of referent configuration) to investigate the multi-digit
      synergies at two levels of a hypothetical hierarchy involved in prehensile
      actions. Synergies were analyzed at the thumb-virtual finger (VF) level (VF is an
      imaginary digit with the mechanical action equivalent to that of the four actual
      fingers) and at the individual finger level. The subjects performed very quick
      vertical movements of a handle into a target. A load could be attached off-center
      to provide a pronation or supination torque. In a few trials, the handle was
      unexpectedly fixed to the table and the digits slipped off the sensors. In such
      trials, the hand stopped at a higher vertical position and rotated into pronation
      or supination depending on the expected torque. The aperture showed non-monotonic
      changes with a large, fast decrease and further increase, ending up with a
      smaller distance between the thumb and the fingers as compared to unperturbed
      trials. Multi-digit synergies were quantified using indices of co-variation
      between digit forces and moments of force across unperturbed trials. Prior to the
      lifting action, high synergy indices were observed at the individual finger level
      while modest indices were observed at the thumb-VF level. During the lifting
      action, the synergies at the individual finger level disappeared while the
      synergy indices became higher at the thumb-VF level. The results support the
      basic premise that, within a given task, setting a referent configuration may be
      described with a few referent values of variables that influence the equilibrium
      state, to which the system is attracted. Moreover, the referent configuration
      hypothesis can help interpret the data related to the trade-off between synergies
      at different hierarchical levels.

PMID- 20033398
TI  - Genes acquired by horizontal transfer are potentially involved in the evolution
      of phytopathogenicity in Moniliophthora perniciosa and Moniliophthora roreri, two
      of the major pathogens of cacao.
AB  - Moniliophthora perniciosa and Moniliophthora roreri are phytopathogenic
      basidiomycete species that infect cacao causing two important diseases in this
      crop: "Witches' Broom" and "Frosty Pod Rot", respectively. The ability of species
      from this genus (Moniliophthora) to cause disease is exceptional in the family
      Marasmiaceae. Species in closely related genera including, Marasmius,
      Crinipellis, and Chaetocalathus, are mainly saprotrophs and are not known to
      cause disease. In this study, the possibility that this phytopathogenic lifestyle
      has been acquired by horizontal gene transfer (HGT) was investigated. A stringent
      genome comparison pipeline was used to identify potential genes that have been
      obtained by Moniliophthora through HGT. This search led to the identification of
      three genes: a metallo-dependent hydrolase (MDH), a mannitol phosphate
      dehydrogenase (MPDH), and a family of necrosis-inducing proteins (NEPs).
      Phylogenetic analysis of these genes suggests that Moniliophthora acquired NEPs
      from oomycetes, MDH from actinobacteria and MPDH from firmicutes. Based on the
      known gene functions and on previous studies of M. perniciosa infection and
      development, a correlation between gene acquisition and the evolution of the
      phytopathogenic genus Moniliophthora can be postulated.

PMID- 20033399
TI  - Single-nucleotide polymorphisms in the IL2RA gene are associated with age at
      diagnosis in late-onset Finnish type 1 diabetes subjects.
AB  - The onset of type 1 diabetes can occur at any age, with as many as half of all
      cases diagnosed after age 15. Despite this wide distribution in age at diagnosis,
      most genetic studies focus on cases diagnosed in childhood or during early
      adulthood. To better understand the genetics of late-onset type 1 diabetes, we
      collected a Finnish case/control cohort with all cases diagnosed between ages 15
      and 40. We genotyped 591 probands and 1,538 control subjects at regions well
      established as susceptibility loci in early onset type 1 diabetes. These loci
      were then tested for disease association and age-at-diagnosis effects. Using
      logistic regression, we found that single-nucleotide polymorphisms (SNPs) at the
      INS, PTPN22, and IFIH1 loci were associated with late-onset disease (OR (95%CI) =
      0.57(0.47-0.69), p = 2.77 x 10(-9); OR (95%CI) = 1.50 (1.27-1.78), p = 3.98 x 10(
      6); and OR (95%CI) = 0.81(0.71-0.93), p = 0.0028, respectively). In contrast, a
      disease association was not detected for two SNPs at the IL2RA locus (rs11594656
      and rs41295061). Despite this, we did find an independent age-at-diagnosis effect
      for each IL2RA SNP using a multivariate Cox proportional hazards model (p =
      0.003, 0.002, respectively). Taken together, polymorphisms at the IL2RA locus
      were a major determinant of age at diagnosis in our cohort with an effect at par
      with the HLA-DQ2/DQ8 genotype as measured by hazard ratios. These findings
      suggest that the IL2RA locus controls both the susceptibility to disease and its
      time of occurrence. Thus, we believe the IL2/IL2R axis represents a potential
      therapeutic target for delaying the onset of disease.

PMID- 20033400
TI  - Engineering expression of the heavy metal transporter MerC in Saccharomyces
      cerevisiae for increased cadmium accumulation.
AB  - The merC gene from the Tn21-encoded mer operon has potential uses as a molecular
      tool for bioremediation. It was overexpressed as the fusion proteins MerC-Sso1p
      or MerC-Vam3p in Saccharomyces cerevisiae. Green fluorescent protein (GFP)-MerC
      Sso1p fusion proteins located primarily in the plasma membrane, although some
      protein was detected in the endoplasmic reticulum. In contrast, GFP-MerC-Vam3p
      was expressed in the vacuolar membranes. These results suggest that yeast Sso1p
      and Vam3p are essential for targeting molecules to the plasma and vacuolar
      membranes, respectively. Significantly more cadmium ions were accumulated by
      yeast cells expressing MerC-Sso1p than with MerC-Vam3p or control cells. These
      results suggest that expression of MerC in the plasma membrane may be a
      particularly promising strategy for improving accumulation of cadmium in yeast.

PMID- 20033401
TI  - Achievements and perspectives to overcome the poor solvent resistance in acetone
      and butanol-producing microorganisms.
AB  - Anaerobic bacteria such as the solventogenic clostridia can ferment a wide range
      of carbon sources (e.g., glucose, galactose, cellobiose, mannose, xylose, and
      arabinose) to produce carboxylic acids (acetic and butyric) and solvents such as
      acetone, butanol, and ethanol (ABE). The fermentation process typically proceeds
      in two phases (acidogenic and solventogenic) in a batch mode. Poor solvent
      resistance by the solventogenic clostridia and other fermenting microorganisms is
      a major limiting factor in the profitability of ABE production by fermentation.
      The toxic effect of solvents, especially butanol, limits the concentration of
      these solvents in the fermentation broth, limiting solvent yields and adding to
      the cost of solvent recovery from dilute solutions. The accepted dogma is that
      toxicity in the ABE fermentation is due to chaotropic effects of butanol on the
      cell membranes of the fermenting microorganisms, which poses a challenge for the
      biotechnological whole-cell bio-production of butanol. This mini-review is
      focused on (1) the effects of solvents on inhibition of cell metabolism (nutrient
      transport, ion transport, and energy metabolism); (2) cell membrane fluidity,
      death, and solvent tolerance associated with the ability of cells to tolerate
      high concentrations of solvents without significant loss of cell function; and
      (3) strategies for overcoming poor solvent resistance in acetone and butanol
      producing microorganisms.

PMID- 20033402
TI  - A standard quantitative method to measure acid tolerance of probiotic cells.
AB  - The aim of this work was to develop a standard quantitative method to measure the
      acid tolerance of probiotic cells when exposed to a simulated gastric fluid.
      Three model strains of different cell concentrations were exposed to a standard
      simulated gastric fluid of fixed volume. The fluid pH ranged from pH 1.5 to 2.5.
      In general, the death kinetics followed an exponential trend. The overall death
      constant, k (d), for all strains was found to be in a power relationship with the
      pH value and the initial cell concentration, and it can be expressed as
      k(d)=k(AII) (pH(-9.0)N(0)(-0.19)) where k (AII) is defined as the acid
      intolerance indicator and N (0) is the initial cell concentration (CFU/ml). This
      equation was validated with the experimental data with an average R (2) of 0.98.
      The acid intolerance of cells can be quantitatively expressed by the k (AII)
      values, where higher value indicates higher intolerance. In conclusion, a
      standard quantitative method has been developed to measure the acid tolerance of
      probiotic cells. This could facilitate the selection of probiotic strains and
      processing technologies.

PMID- 20033403
TI  - Fatty acid alkyl esters: perspectives for production of alternative biofuels.
AB  - The global economy heads for a severe energy crisis: whereas the energy demand is
      going to rise, easily accessible sources of crude oil are expected to be depleted
      in only 10-20 years. Since a serious decline of oil supply and an associated
      collapse of the economy might be reality very soon, alternative energies and also
      biofuels that replace fossil fuels must be established. In addition, these
      alternatives should not further impair the environment and climate. About 90% of
      the biofuel market is currently captured by bioethanol and biodiesel. Biodiesel
      is composed of fatty acid alkyl esters (FAAE) and can be synthesized by chemical,
      enzymatic, or in vivo catalysis mainly from renewable resources. Biodiesel is
      already established as it is compatible with the existing fuel infrastructure,
      non-toxic, and has superior combustion characteristics than fossil diesel; and in
      2008, the global production was 12.2 million tons. The biotechnological
      production of FAAE from low cost and abundant feedstocks like biomass will enable
      an appreciable substitution of petroleum diesel. To overcome high costs for
      immobilized enzymes, the in vivo synthesis of FAAE using bacteria represents a
      promising approach. This article points to the potential of different FAAE as
      alternative biofuels, e.g., by comparing their fuel properties. In addition to
      conventional production processes, this review presents natural and genetically
      engineered biological systems capable of in vivo FAAE synthesis.

PMID- 20033404
TI  - Display of Candida antarctica lipase B on Pichia pastoris and its application to
      flavor ester synthesis.
AB  - Two alternative cell-surface display systems were developed in Pichia pastoris
      using the alpha-agglutinin and Flo1p (FS) anchor systems, respectively. Both the
      anchor cell wall proteins were obtained originally from Saccharomyces cerevisiae.
      Candida antarctica lipase B (CALB) was displayed functionally on the cell surface
      of P. pastoris using the anchor proteins alpha-agglutinin and FS. The activity of
      CALB displayed on P. pastoris was tenfold higher than that of S. cerevisiae. The
      hydrolytic and synthetic activities of CALB fused with alpha-agglutinin and FS
      anchored on P. pastoris were investigated. The hydrolytic activities of both
      lipases displayed on yeast cells surface were more than 200 U/g dry cell after
      120 h of culture (200 and 270 U/g dry cell, respectively). However, the synthetic
      activity of CALB fused with alpha-agglutinin on P. pastoris was threefold higher
      than that of the FS fusion protein when applied to the synthesis of ethyl
      caproate. Similarly, the CALB displayed on P. pastoris using alpha-agglutinin had
      a higher catalytic efficiency with respect to the synthesis of other short-chain
      flavor esters than that displayed using the FS anchor. Interestingly, for some
      short-chain esters, the synthetic activity of displaying CALB fused with alpha
      agglutinin on P. pastoris was even higher than that of the commercial CALB
      Novozyme 435.

PMID- 20033405
TI  - Change in glucose metabolism measured by 18F-FDG PET/CT as a predictor of
      histopathologic response to neoadjuvant treatment in rectal cancer.
AB  - PURPOSE: In order to analyze the changes of glucose metabolism by maximum
      standardized uptake value (SUVmax) of 18F-FDG PET/CT in patients with rectal
      cancer submitted to neoadjuvant radiochemotherapy (nRCT) and to correlate SUV
      changes with tumor regression grade (TRG). METHODS AND MATERIAL: Three sequential
      18F-FDG PET/CT studies were performed in 31 patients with rectal cancer at the
      following time point: before starting the treatment (PET/CT1), during the
      treatment (PET/CT2), and after completion of neoadjuvant treatment (PET/CT3). The
      SUVmax values of the rectal lesion in the PET/CT1 (SUV1), PET/CT2 (SUV2), and
      PET/CT3 (SUV3) were obtained; deltaSUV1 [(SUV1 - SUV2)/SUV1] and deltaSUV2 [(SUV1
      - SUV3)/SUV1] were also calculated. Metabolic parameters were compared to TRG.
      RESULTS: Significant differences in pathologic responder and non-responder
      patients were found only for SUV2 (6.4 +/- 2.9 in responder and 10.7 +/- 4.8 in
      non-responder patients, respectively; P = 0.006) and SUV3 (3.6 +/- 1.4 in
      responder and 6.6 +/- 2.1 in non-responder patients, respectively; P = 0.0009).
      The best predictor for TRG response was SUV3 (threshold of 4.4) with sensitivity,
      specificity, accuracy, negative predictive value, and positive predictive value
      of 77.3%, 88.9%, 80.7%, 61.5%, and 94.4%, respectively. CONCLUSION: 18F-FDG
      PET/CT is a reliable and accurate technique to assess the response to nRCT in
      rectal cancer. In our population, the absolute value of SUVmax after treatment
      was the best predictor of pathological response.

PMID- 20033406
TI  - Total thyroidectomy is superior to subtotal thyroidectomy for management of
      Graves' disease in the United States.
AB  - BACKGROUND: In the United States, Graves' disease is most commonly treated with
      radioiodine, yet thyroidectomy remains an important option for correcting
      hyperthyroidism. In many countries, limited access to thyroid hormone makes
      subtotal thyroidectomy the procedure of choice. In the United States, where
      levothyroxine is widely available, we hypothesized that total (TT) or near-total
      thyroidectomy (NT) is superior to subtotal thyroidectomy (ST) for long-term
      control of Graves' disease. METHODS: A retrospective review of patients who
      underwent ST, NT, or TT for Graves' disease between 1990 and 2008 was conducted.
      Differences in rates of disease recurrence were assessed by analysis of variance
      (ANOVA). Rates of parathyroid autotransplantation, complications, gland weight,
      and final pathology were determined. RESULTS: A total of 136 patients with
      Graves' disease were treated with thyroidectomy. Average age was 36.4 +/- 11.3
      years (range: 16-81 years) and 88% were female. From 1990 to 1994, 10 patients
      underwent ST and 6 had NT. Since then, all patients have undergone TT (n = 120).
      There was a significantly higher rate of recurrence for ST (30%) compared to NT
      (0%; P = 0.15) and TT (0%; P < 0.0001). Parathyroid autotransplantation was
      performed in 36 (26.5%) patients, only 2 of whom underwent ST or NT. Transient
      postoperative hypocalcemia was more common after TT (P = 0.04). No patient in any
      group had permanent hypoparathyroidism. Two TT pts had transient recurrent
      laryngeal nerve palsy. CONCLUSIONS: Subtotal thyroidectomy resulted in 30% long
      term failure to correct Graves' hyperthyroidism. We saw no recurrences and no
      increase in postoperative complications in the TT group. We feel that TT is safe
      and superior to ST for management of Graves' disease in the United States.

PMID- 20033407
TI  - Intraoperative near-infrared fluorescent cholangiography (NIRFC) in mouse models
      of bile duct injury.
AB  - BACKGROUND: Accidental injury to the common bile duct is a rare but serious
      complication of laparoscopic cholecystectomy. Accurate visualization of the
      biliary ducts may prevent injury or allow its early detection. Conventional X-ray
      cholangiography is often used and can mitigate the severity of injury when
      correctly interpreted. However, it may be useful to have an imaging method that
      could provide real-time extrahepatic bile duct visualization without changing the
      field of view from the laparoscope. The purpose of the present study was to test
      a new near-infrared (NIR) fluorescent agent that is rapidly excreted via the
      biliary route in preclinical models to evaluate intraoperative real-time near
      infrared fluorescent cholangiography (NIRFC). METHODS: To investigate probe
      function and excretion, a lipophilic near-infrared fluorescent agent with
      hepatobiliary excretion was injected intravenously into one group of C57/BL6
      control mice and four groups of C57/BL6 mice under the following experimentally
      induced conditions: (1) chronic biliary obstruction, (2) acute biliary
      obstruction (3) bile duct perforation, and (4) choledocholithiasis, respectively.
      The biliary system was imaged intravitally for 1 h with near-infrared
      fluorescence (NIRF) with an intraoperative small animal imaging system
      (excitation 649 nm, emission 675 nm). RESULTS: The extrahepatic ducts and
      extraluminal bile were clearly visible due to the robust fluorescence of the
      excreted fluorochrome. Twenty-five minutes after intravenous injection, the
      target-to-background ratio peaked at 6.40 +/- 0.83 but signal was clearly visible
      for ~60 min. The agent facilitated rapid identification of biliary obstruction
      and bile duct perforation. Implanted beads simulating choledocholithiasis were
      promptly identifiable within the common bile duct lumen. CONCLUSIONS: Near
      infrared fluorescent agents with hepatobiliary excretion may be used
      intraoperatively to visualize extrahepatic biliary anatomy and physiology. Used
      in conjunction with laparoscopic imaging technologies, the use of this technique
      should enhance hepatobiliary surgery.

PMID- 20033408
TI  - Inflammatory myofibroblastic tumor of the liver: a cohort study.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare condition. The aim
      of the present study was to evaluate the clinical characteristics and surgical
      outcomes for IMT of the liver in our large cohort of patients. METHODS: From
      January 2001 to December 2007, all patients with a pathological diagnosis of IMT
      of the liver who underwent partial hepatectomy were retrospectively analyzed.
      RESULTS: During the study period, 64 patients underwent partial hepatectomy for
      IMT of the liver in our tertiary referral center. The commonest clinical
      presentation was abdominal pain (53%), followed by fever (41%); 15.6% of patients
      were asymptomatic. Preoperative diagnosis of IMT was suspected in only five
      patients (8%). The indications for surgery included suspicion of malignancy
      (60.9%), uncertain diagnosis (40.6%), symptomatic disease (26.6%), and
      spontaneous rupture (3.1%). The postoperative complication rate was low (17.2%).
      There was no hospital mortality. After a median follow-up of 30 months, no
      patient developed recurrence. CONCLUSIONS: Although there are various treatment
      options for IMT of the liver, surgical resection for good risk patients is
      preferred.

PMID- 20033409
TI  - High versus standard dose methylprednisolone in the acute phase of idiopathic
      thrombotic thrombocytopenic purpura: a randomized study.
AB  - Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic
      thrombocytopenic purpura (TTP). Because not all patients achieve remission, other
      treatment modalities have been used in addition to PE, but no randomized clinical
      trial evaluated their efficacy. The aim of this multicentric study was to compare
      the effectiveness of standard- versus high-dose methylprednisolone as an
      adjunctive treatment to PE in the acute phase of TTP. Sixty patients with
      idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die
      intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to
      PE. Both dosages of steroids were well tolerated. At the end of induction therapy
      (day 23), the percentage of patients failing to achieve complete remission was
      significantly higher in the standard dose (16 of 30) than in the high-dose group
      (seven of 30). Also, the number of cases without a good response at day 9 and the
      number of deaths were higher in the standard-dose arm, but the differences did
      not reach the statistical significance. Results of present study indicate that
      the association of PE with high-dose instead of standard-dose steroids reduces
      the percentage of TTP patients that fail to achieve complete remission.

PMID- 20033410
TI  - The impact of high-dose methotrexate on intracellular 6-mercaptopurine
      disposition during interval therapy of childhood acute lymphoblastic leukemia.
AB  - PURPOSE: Low-dose methotrexate (MTX) therapy is the cornerstone treatment of
      acute lymphoblastic leukemia (ALL) and may enhance the activation of 6
      mercaptopurine (6-MP) to 6-thioguanine nucleotides (6-TGN). Yet, data have
      established that high-dose MTX (HDMTX) hampers the accumulation of 6-TGN in red
      blood cells (RBC) and lymphoblasts. METHODS: To clarify the pharmacokinetic
      interactions between these two antimetabolites, we serially measured RBC 6-TGN
      and MTX polyglutamates (MTXPG) levels following repeated courses of HDMTX (5
      g/m(2) over 24 h) with daily oral 6-MP (25 mg/m(2)) during interval therapy in 20
      children with ALL. RESULTS: HDMTX produced a rapid reduction in RBC 6-TGN 24 h
      after the start of MTX, and this effect was sustained at least by the third day
      (median decrease -21%; P < 0.001). However, a return to pre-infusion of 6-TGN
      levels was observed by the time of the following HDMTX course 14 days later (P <
      0.001). RBC MTX polyglutamates accumulation followed Michaelis-Menten kinetics
      but was not associated with the change in pre-infusion 6-TGN levels which
      remained stable during the interval period. CONCLUSION: HDMTX does not appear to
      enhance 6-MP activation to 6-TGN. Moreover, given that the deleterious effect of
      HDMTX on intracellular 6-MP disposition has been shown to be several folds
      greater in lymphoblasts than in RBC. Our data warrant additional studies
      elucidating the optimal MTX dose synergizing with 6-MP.

PMID- 20033411
TI  - Concurrent chemoradiation followed by adjuvant chemotherapy in patients with
      locoregionally advanced nasopharyngeal carcinoma in Korea.
AB  - PURPOSE: Concomitant approach using cisplatin and 5-fluorouracil (5-FU) has shown
      an excellent local control rate and significantly reduced distant metastasis in
      patients with locally advanced nasopharyngeal carcinoma (NPC). However, optimal
      schedule and dosing of chemotherapy still need to be developed to reduce distant
      metastasis. This retrospective study was conducted to evaluate the efficacy,
      toxicity, and tolerability of a concurrent chemoradiation therapy (CCRT) regimen
      using cisplatin and 5-FU followed by adjuvant chemotherapy (AC) in patients with
      locoregionally advanced NPC. METHODS: Forty-three NPC patients who had AJCC stage
      T3/T4 or N2/N3 and M0 disease were evaluated. The chemotherapy during CCRT
      consisted of cisplatin (75 mg/m(2) on day 1) plus 5-FU (750 mg/m(2)/day on day 1
      5), delivered every 4 weeks for two cycles. Three cycles of AC were given with
      cisplatin (75 mg/m(2)), epirubicin (37.5 mg/m(2)) on day 1, and bleomycin (7.5
      mg/m(2) bolus iv. on day 1 followed by 9 mg/m(2) on day 1-5 by continuous
      infusion) every 3 weeks. RESULTS: The overall response rate after CCRT was 95%
      (22 CRs and 19 PRs in 43) and 100% (16 CRs and 8 PRs in 24) after AC. Grade 3/4
      neutropenia, mucositis, and weight loss were observed during CCRT phase in 18,
      44, and 26% of patients, respectively. AC caused grade 3/4 neutropenia and emesis
      in 12.5 and 20.8% of patients, respectively. CONCLUSIONS: CCRT regimen using
      cisplatin and 5-FU followed by three cycles of BEC chemotherapy was effective in
      locally advanced NPC patients, with acceptable and reversible acute toxicities.

PMID- 20033412
TI  - Clarithromycin in adult-onset Still's disease: a study of 6 cases.
AB  - Adult-onset Still's disease (AOSD) is a rare rheumatological condition
      characterized by an acute systemic involvement. There are no treatment
      guidelines. Glucocorticoids (GC), methotrexate (MTX), cyclosporin A and biologic
      agents have been successfully used, often in association. We treated six cases of
      AOSD with clarithromycin (CM) in combination with low-mild dose of GC and MTX.
      Four of them were not responsive to high-dose GC added to DMARDs, while two of
      them were treated with low-mild dose of GC added to CM from the beginning. CM,
      500 mg b.i.d., was added to a mild-low dose of GC and to MTX. The dose of the
      drugs was reduced (and stopped where possible) following clinical and laboratory
      parameters. ACR criteria were used to assess clinical improvement. At 6 months 5
      patients reached ACR 70% and could stop any therapy in 6-18 months; 1 continued
      chronic therapy with low-dose GC added to CM and MTX to maintain ACR 50%. CM can
      be a useful drug for the treatment of AOSD, even in patients not responsive to
      high-dose GC and DMARDs. No definitive conclusion can be drawn based on the
      present study.

PMID- 20033413
TI  - The effects of beta-glucan isolated from Pleurotus ostreatus on methotrexate
      treatment in rats with adjuvant arthritis.
AB  - The purpose of this study was to evaluate the effect of beta-(1,3/1,6)-D: -glucan
      isolated from Pleurotus ostreatus (beta-glucan-PO) on prophylactic treatment of
      adjuvant arthritis (AA) with methotrexate (MTX) in rats. Groups of rats with AA
      were treated with methotrexate (1 mg/kg/week), beta-glucan-PO (1 mg/kg every
      second day) or their combination for the period of 28 days from adjuvant
      application. Body mass, hind paw swelling, arthrogram scores and a level of serum
      albumin were measured as markers of inflammation and arthritis. Treatment with
      low dose of MTX significantly inhibited the markers of both inflammation and
      arthritis. MTX and its combination with beta-glucan-PO significantly increased
      body mass of arthritic rats. beta-glucan-PO administered alone significantly
      decreased both the hind paw swelling and arthritic score. In combination with
      MTX, beta-glucan-PO markedly potentiated the beneficial effects of MTX, which
      resulted in a more significant reduction of hind paw swelling and arthritic
      scores. The concentration of albumin in the serum of arthritic controls was
      significantly lower than in healthy controls. Both MTX alone and the combination
      treatment with MTX + beta-glucan-PO significantly inhibited the decrease in serum
      albumin. beta-Glucan-PO increased the treatment efficacy of basal treatment of AA
      with MTX.

PMID- 20033414
TI  - C1q and anti-C1q antibody levels are correlated with disease severity in Chinese
      pediatric systemic lupus erythematosus.
AB  - The aim of this study was to measure the level of serum complement lq(Clq) and
      anti-C1q antibodies (ClqAb) in pediatric systemic lupus erythematosus (PSLE), and
      then analyze the correlation between the levels of serum Clq and ClqAb with
      disease activity and kidney damage. We investigated 90 PSLE patients, including
      43 patients in active stage and 47 patients in remission. Our results showed that
      the level of serum Clq of PSLE patients was significantly lower than the level of
      healthy children and children with other rheumatic diseases. In contrast, the
      level of ClqAb of PSLE patients was significantly higher than the other groups.
      The level of serum Clq was negatively correlated with systemic lupus
      erythematosus (SLE) disease active index (SLEDAI) and the level of ClqAb was
      positively correlated with SLEDAI and kidney damage. The sensitivity of using
      ClqAb levels to diagnose PSLE was 95.6% and the specificity was 97.5%. 93.0% SLE
      patients who had high C1qAb levels also showed kidney damage. Therefore, the
      levels of C1q and C1qAb in serum reflect the disease severity of SLE. Decreased
      Clq and increased C1qAb is closely correlated with lupus nephritis (LN) in
      children and may have diagnosis values for child LN.

PMID- 20033415
TI  - Vitamin D level: is it related to disease activity in inflammatory joint disease?
AB  - The objectives of this study are to assess the vitamin D status in patients (pts)
      with inflammatory joint diseases (IJD), and its correlation with disease
      activity. 121 consecutive pts (85 rheumatoid arthritis (RA), 22 psoriatic
      arthritis (PSA), 14 ankylosing spondylitis (AS)) underwent clinical and
      laboratory evaluation which included kidney and liver function tests, serum
      calcium and phosphor levels, 25(OH)D and parathyroid hormone (PTH). Disease
      activity was assessed by DAS 28 in RA and PSA pts and by BASDAI in AS pts,
      sedimentation rate (ESR) and CRP. According to activity indexes, pts were divided
      into subgroups with low (DAS28 < 3.2 and BASDAI < 4), and moderate-to-high
      disease activity (DAS28 > 3.2 and BASDAI > 4). Associations between serum levels
      of 25(OH)D and age, gender, ethnicity, type and disease duration, treatment,
      (anti-tumor necrosis factoralpha (TNFalpha) agents or DMARDs), seasonal
      variations, and disease activity were assessed. Vitamin D deficiency was found in
      51 pts (42.1%). The incidence was higher among Arab pts (76.7%) compared to Jews
      (23%). The difference of 25(OH)D levels between Arabs (mean 9.4 +/- 4.2 ng/ml)
      and Jews (mean 17.8 +/- 8.4 ng/ml) was statistically significant (p < 0.0001). We
      did not find correlation between vitamin D levels and the other evaluated
      factors. A surprisingly high incidence of vitamin D deficiency was found in IJD
      patients in a sunny Mediterranean country. This finding justifies the inclusion
      of vitamin D in the routine lab work-up of pts with IJD. The only statistical
      significant correlation was found between vitamin D level and ethnic origin.
      Further studies are needed to look for genetic polymorphism of vitamin D
      receptors.

PMID- 20033416
TI  - Identification of qRT-PCR reference genes for analysis of opioid gene expression
      in a hibernator.
AB  - Previous work has suggested that central and peripheral opioid signaling are
      involved in regulating torpor behavior and tissue protection associated with the
      hibernation phenotype. We used quantitative real-time PCR (qRT-PCR) to measure
      mRNA levels of opioid peptide precursors and receptors in the brain and heart of
      summer ground squirrels (Ictidomys tridecemlineatus) and winter hibernating
      squirrels in the torpid or interbout arousal states. The use of appropriate
      reference genes for normalization of qRT-PCR gene expression data can have
      profound effects on the analysis and interpretation of results. This may be
      particularly important when experimental subjects, such as hibernating animals,
      undergo significant morphological and/or functional changes during the study.
      Therefore, an additional goal of this study was to identify stable reference
      genes for use in qRT-PCR studies of the 13-lined ground squirrel. Expression
      levels of 10 potential reference genes were measured in the small intestine,
      liver, brain, and heart, and the optimal combinations of the most stable
      reference genes were identified by the GeNorm Excel applet. Based on this
      analysis, we provide recommendations for reference genes to use in each tissue
      that would be suitable for comparative studies among different activity states.
      When appropriate normalization of mRNA levels was used, there were no changes in
      opioid-related genes in heart among the three activity states; in brain, DOR
      expression was highest during torpor, lowest in interbout arousal and
      intermediate in summer. The results support the idea that changes in DOR
      expression may regulate the level of neuronal activity in brain during the annual
      hibernation cycle and may contribute to hibernation-associated tissue protection.

PMID- 20033417
TI  - No effect of the farming system (organic/conventional) on the bioavailability of
      apple (Malus domestica Bork., cultivar Golden Delicious) polyphenols in healthy
      men: a comparative study.
AB  - BACKGROUND: The organic food sales have been increasing during the recent years.
      It has been hypothesised that organically grown fruits are healthier based on
      their higher content of phytochemicals. However, data on the bioavailability of
      phytochemicals from organically or conventionally produced plant foods are
      scarce. METHODS: Two human intervention studies were performed to compare the
      bioavailability of polyphenols in healthy men after ingestion of apples from
      different farming systems. The administered apples were grown organically and
      conventionally under defined conditions and characterised regarding their
      polyphenol content and antioxidant capacity. No significant differences in the
      polyphenol content and the antioxidant capacity from the organic and conventional
      farming system were observed. RESULTS: In the short-term intervention study, six
      men consumed either organically or conventionally produced apples in a randomized
      cross-over study. After intake of 1 kg apples, phloretin (C (max) 13 + or - 5
      nmol/l, t (max) 1.7 + or - 1.2 h) and coumaric acid (C (max )35 + or - 12 nmol/l,
      t (max) 3.0 + or - 0.8 h) plasma concentrations increased significantly (P <
      0.0001) in both intervention groups, without differences between the two farming
      systems. In the long-term intervention study, 43 healthy volunteers consumed
      organically or conventionally produced apples (500 g/day; 4 weeks) or no apples
      in a double-blind, randomized intervention study. In this study, 24 h after the
      last dosing regime, the apple intake did not result in increasing polyphenol
      concentrations in plasma and urine compared to the control group suggesting no
      accumulation of apple polyphenols or degradation products in humans. CONCLUSION:
      Our study suggests that the two farming systems (organic/conventional) do not
      result in differences in the bioavailability of apple polyphenols.

PMID- 20033418
TI  - Outcome of severe preeclampsia manifested as nephrotic syndrome.
AB  - OBJECTIVES: To discuss the clinical features of severe preeclampsia and its
      outcome manifested as nephrotic syndrome (NSP). METHODS: Clinical data of 22 NSP
      patients treated in our hospital from January 2003 to March 2008 were collected
      to retrospectively analyze the blood pressure, serum albumin, urea nitrogen,
      cholesterol, 24 h urine protein, etc. before and after pregnancy. RESULTS: (1)
      The outcome of pregnant women: the blood pressure of patients in all 22 cases
      recovered within 6 weeks; edema usually regressed within 6 weeks, however, only 1
      patient recovered on week 10; urine protein usually disappeared within 6 weeks,
      however, it kept remaining in the urine of patients in 2 cases after 10 weeks;
      the recovery of blood lipid, serum uric acid and plasma albumin often occurred
      within 4-10 weeks, while only a few patients did not recover; no pregnant woman
      died, indicating good prognosis. (2) The outcome of perinatal infant: 7 perinatal
      infants died (31.8%), and 9 neonatal infants were asphyxiated (40.9%), and 15
      neonatal infants with low weight were born (68.2%). CONCLUSIONS: All indexes of
      NSP patients usually recovered within 6 weeks after pregnancy cessation.

PMID- 20033419
TI  - Malignant mixed mullerian tumor of the fallopian tube: report of two cases and
      review of literature.
AB  - PURPOSE: Malignant mixed mullerian tumors (MMMT) of the female genital tract is
      rare and it is extremely rare in the fallopian tube, with fewer than 53 cases
      reported in the literature. METHODS: We had experienced two cases of MMMT of the
      fallopian tube. The clinical features, pathologic findings, diagnosis, therapy,
      and outcome were reviewed. RESULTS: The clinical features and diagnosis were
      similar to those of primary carcinoma of the fallopian tube. Histologically, the
      two patients had homologous and heterologous elements mixed mullerian tumors.
      Treatment has focused on surgery with postoperative chemotherapy. Prognosis is
      poor, with fewer than half of patients surviving 2 years. CONCLUSIONS: MMMT of
      fallopian tube is an uncommon carcinoma in the female genital tract. Cervical
      cytology and endometrial curettage could raise the suspicion of a tubal
      malignancy, but diagnosis is not usually made until the time of surgery. The
      patient survival will improve after surgery and postoperative chemotherapy.

PMID- 20033420
TI  - A case of ruptured uterus at 27 weeks of gestation complicated by placenta
      accreta.
AB  - INTRODUCTION: Placenta accreta is a rare complication, which can lead to maternal
      morbidity and mortality. MATERIALS AND METHODS: This is a interesting case report
      where uterine rupture in the fundal region complicated with placenta accreta.
      CONCLUSION: Undiagnosed placenta accreta can lead to catastrophic consequences.

PMID- 20033421
TI  - Influence of self-reported snoring and witnessed sleep apnea on gestational
      hypertension and fetal outcome in pregnancy.
AB  - INTRODUCTION: Hormonal and physical changes during pregnancy are associated with
      some sleep-related breathing disorders (SRBD) such as snoring and sleep apnea,
      and SRBD are associated with recurrent episodes of oxyhemoglobin desaturation and
      increased sympathic activity. We aimed to search the incidence of self-reported
      snoring and witnessed apnea in the third trimester of pregnancy and to analyze
      their influence on fetal outcome and gestational hypertension (GH). METHODS: Two
      hundred pregnant women (group 1) during their stay for labor and 200 age-matched
      control women (group 2) were included in the study. All patients were asked to
      complete a detailed questionnaire that covers demographic features. We measured
      neck circumference and performed Epworth sleepiness scale (ESS) to determine
      excessive daytime sleepiness in all patients. RESULTS: The mean age was 27.4 +/-
      6.7 and 26.3 +/- 5.8 for group 1 and 2, respectively. Habitual snoring was
      detected only in group 1 in 5 patients; 36 pregnant women and 7 control patients
      reported occasional snoring. Both habitual and occasional snoring was
      significantly observed to be increased in pregnancy. Witnessed sleep apnea was
      been observed only in 1 patient in group 1. The mean neck circumference was 37.4
      +/- 3.2, 35.1 +/- 2.1 cm and ESS was 6.7 +/- 3.01, 5.1 +/- 2.1 for group 1 and 2,
      respectively (p < 0.05). There was no significant correlation between snoring and
      GH. There was no significant relationship between all investigated parameters and
      fetal outcome. We found that excessive weight gain during pregnancy is
      significantly associated with snoring. CONCLUSION: We concluded that, although
      pregnant women, especially who gain excessive weight during their pregnancy,
      significantly snore more than nonpregnant women, this did not affect fetal
      outcome.

PMID- 20033423
TI  - The nasopharyngeal bacterial flora in children with otitis media with effusion.

PMID- 20033422
TI  - Spontaneous rupture of unscarred uterus at 27 weeks of gestation.

PMID- 20033424
TI  - Strong association between cancer and genomic instability.
AB  - After a first wave of radiation-induced chromosomal aberrations, a second wave
      appears 20-30 cell generations after radiation exposure and persists thereafter.
      This late effect is usually termed "genomic instability". A better term is
      "increased genomic instability". This effect has been observed in many cell
      systems in vitro and in vivo for quite a number of biological endpoints. The
      radiation-induced increase in genomic instability is apparently a general
      phenomenon. In the development of cancer, several mutations are involved. With
      increasing genomic instability, the probability for further mutations is
      enhanced. Several studies show that genomic instability is increased not only in
      the cancer cells but also in "normal" cells of cancer patients e.g. peripheral
      lymphocytes. This has for example been shown in uranium miners with bronchial
      carcinomas, but also in untreated head and neck cancer patients. The association
      between cancer and genomic instability is also found in individuals with a
      genetic predisposition for increased radiosensitivity. Several such syndromes
      have been found. In all cases, an increased genomic instability, cancer proneness
      and increased radiosensitivity coincide. In these syndromes, deficiencies in
      certain DNA-repair pathways occur as well as deregulations of the cell cycle.
      Especially, mutations are seen in genes encoding proteins, which are involved in
      the G(1)/S-phase checkpoint. Genomic instability apparently promotes cancer
      development. In this context, it is interesting that hypoxia, increased genomic
      instability and cancer are also associated. All these processes are energy
      dependent. Some strong evidence exists that the structure and length of telomeres
      is connected to the development of genomic instability.

PMID- 20033425
TI  - Comparison of hang-back and conventional bimedial rectus recession in infantile
      esotropia.
AB  - PURPOSE: To compare surgical outcome of hang-back and conventional bimedial
      rectus muscle recession in infantile esotropia. PATIENTS AND METHODS: The charts
      of 67 consecutive patients with infantile esotropia who underwent bilateral
      medial rectus muscle from 1990 through 2005 were retrospectively reviewed. Thirty
      patients were operated by hang-back technique (group 1) and 37 by conventional
      bimedial rectus recession in which the tendon was sutured directly to the globe
      (group 2). In each group, the angle of esotropia (PD - prism diopters) before and
      6 months after surgery and the success rate (deviation of < or =10 PD) were
      documented. RESULTS: Esotropia improved an average of 39.7 (SD 14.9) PD in group
      1 (from a preoperative 42.7 (SD 11.6) PD to 3.0 (SD 8.5) PD postoperatively) and
      45.5 (SD 19.3) PD in group 2 (from a preoperative 54.3 (SD 16.8) PD to 8.7 (SD
      12.1) PD postoperatively) (p = 0.18, independent sample t-test). Success rate
      (defined as deviation of < or =10 PD at 6 months postoperative examination) was
      83.3% in group 1 and 70.2% in group 2 (p = 0.21, Chi-square). Multivariate
      logistic regression suggests that surgical outcomes are not significantly
      influenced by age and preoperative angle of esotropia. No complications occurred
      in both groups. CONCLUSION: Hang-back technique is as effective as the
      conventional bimedial rectus muscle recession in correcting infantile esotropia.

PMID- 20033431
TI  - Evaluation of different methods for determining growing degree-day thresholds in
      apricot cultivars.
AB  - The aim of this study was to examine different methods for determining growing
      degree-day (GDD) threshold temperatures for two phenological stages (full bloom
      and harvest) and select the optimal thresholds for a greater number of apricot
      (Prunus armeniaca L.) cultivars grown in the Belgrade region. A 10-year data
      series were used to conduct the study. Several commonly used methods to determine
      the threshold temperatures from field observation were evaluated: (1) the least
      standard deviation in GDD; (2) the least standard deviation in days; (3) the
      least coefficient of variation in GDD; (4) regression coefficient; (5) the least
      standard deviation in days with a mean temperature above the threshold; (6) the
      least coefficient of variation in days with a mean temperature above the
      threshold; and (7) the smallest root mean square error between the observed and
      predicted number of days. In addition, two methods for calculating daily GDD, and
      two methods for calculating daily mean air temperatures were tested to emphasize
      the differences that can arise by different interpretations of basic GDD
      equation. The best agreement with observations was attained by method (7). The
      lower threshold temperature obtained by this method differed among cultivars from
      -5.6 to -1.7 degrees C for full bloom, and from -0.5 to 6.6 degrees C for
      harvest. However, the "Null" method (lower threshold set to 0 degrees C) and
      "Fixed Value" method (lower threshold set to -2 degrees C for full bloom and to 3
      degrees C for harvest) gave very good results. The limitations of the widely used
      method (1) and methods (5) and (6), which generally performed worst, are
      discussed in the paper.

PMID- 20033429
TI  - Integration of newly isolated biocatalyst and resin-based in situ product removal
      technique for the asymmetric synthesis of (R)-methyl mandelate.
AB  - The enantioselective reduction of methyl benzoylformate to (R)-methyl mandelate,
      an important pharmaceutical intermediate and a versatile resolving agent, was
      investigated in this study. After minimizing the reaction-specific constraints
      (constraints dependent on the nature of the substrate and product) by preliminary
      selection of the reaction parameters, an effective whole cell biocatalyst
      (Saccharomyces cerevisiae AS2.1392) was obtained by simple screening procedures.
      Under further optimized conditions, a product concentration of 103 mmol L(-1)
      could be attained within 5 h with a yield of 85.8% and an enantiometric excess of
      95.4%, indicating S. cerevisiae AS2.1392 an efficient biocatalyst for the
      asymmetric synthesis of (R)-methyl mandelate. Furthermore, resin-based in situ
      product removal (ISPR) technique was applied to alleviate the substrate and
      product inhibition or toxicity to the whole cells. The integration of newly
      isolated biocatalyst and proper ISPR technique provides a practical route for the
      preparation of optically active pharmaceutical intermediates.

PMID- 20033432
TI  - Morphological and cytological development and starch accumulation in
      hermaphrodite and staminate flowers of olive (Olea europaea L.).
AB  - In olive (Olea europaea L.), the formation of functionally staminate flowers
      rather than fully functional hermaphrodites is one of the major factors limiting
      fruit set, as flowers with aborted pistils are incapable of producing fruit.
      Studies conducted on various angiosperm species have shown a correlation between
      flower abortion and starch content. Thus, it is important to know if starch
      content plays a role in regulating pistil development in olive and if so, what
      mechanism regulates starch distribution. Cyto-histological observations of
      staminate and hermaphrodite olive flowers show that pistil development in
      staminate flowers is interrupted after the differentiation of the megaspore
      mother cell. At that stage, starch grains were only detected in the ovary, style
      and stigma of the hermaphrodite flowers. No starch was observed in the pistils of
      the staminate flowers. This finding suggests a tight correlation between starch
      content and pistil development. The secondary origin of starch within the flower
      is indicated by low chlorophyll content in the gynoecium, undetectable Rubisco
      activity in the pistils of these two kinds of flowers and by the ultrastructure
      of the plastids observed by transmission electron microscope analysis. The
      plastids have few thylakoid membranes and grana and in the staminate flowers
      appeared very similar to proplastids. Considering differences in starch content
      between staminate and hermaphrodite flowers and the secondary origin of the
      starch, differences in pistil development in the staminate and hermaphrodite
      flowers could be related to differences in the sink strength of these two types
      of flowers.

PMID- 20033433
TI  - Self-incompatibility in a distylous species of Rubiaceae: is there a single
      incompatibility response of the morphs?
AB  - Heterostyly is a genetically controlled floral polymorphism usually associated
      with an incompatibility system. This set of features is known to occur in several
      angiosperm families, but some aspects of its biology has not been well studied.
      The present study investigates cellular aspects of the pollen-pistil interaction
      after compatible and incompatible pollinations of Psychotria nuda, to increase
      our knowledge of heteromorphic self-incompatibility (HetSI). The use of bright
      field, fluorescence and transmission electron microscopy methods allowed us to
      demonstrate that pollen tubes behave differently after incompatible and
      compatible pollinations. Pollen tubes were particularly distinct after
      incompatible pollinations of L- and S-morph flowers. Relative to compatible
      pollen tubes, incompatible L-morph tubes had a drastic reduction in cellular
      contents, but no cell rupture. Incompatible S-morph tubes exhibited dense
      cytoplasm in apical regions, as well as in other regions, accompanied by a
      rupture of the apex. These results support the hypothesis that L- and S-morph
      flowers have different incompatibility mechanisms during HetSI.

PMID- 20033428
TI  - Null mutations in Drosophila Optomotor-blind affect T-domain residues conserved
      in all Tbx proteins.
AB  - The T-box transcription factors TBX2 and TBX3 are overexpressed in many human
      cancers raising the need for a thorough understanding of the cellular function of
      these proteins. In Drosophila, there is one corresponding ortholog, Optomotor
      blind (Omb). Currently, only two missense mutations are known for the two human
      proteins. Making use of the developmental defects caused by inactivation of omb,
      we have isolated and molecularly characterized four new omb mutations, three of
      them are missense mutations of amino acids fully conserved in all Tbx proteins.
      We interpret the functional defects in the framework of the known structure of
      the human TBX3 protein and provide evidence for loss of Omb DNA-binding activity
      in all three newly identified missense mutations.

PMID- 20033434
TI  - The effect of substrate, ADP and uncoupler on the respiration of tomato pollen
      during incubation in vitro at moderately high temperature.
AB  - Pollen of tomato cv. Supermarmande was collected from greenhouse-grown plants at
      various intervals throughout the year and arbitrarily classified as of high,
      medium or low respiratory activity on the basis of CO(2) production during 8 h
      incubation in vitro at 30 degrees C, a temperature that is considered to be
      moderately high for tomato fruit set. After an initial burst of respiration
      during the first stage of hydration at 30 degrees C (>1 h), the respiration rate
      of pollen of all three categories declined, the decrease being greater in the
      lots with a low or medium respiratory activity than in the high category. During
      hydration (10 min after the start of incubation), the addition of succinate or
      reduced beta-nicotinamide adenine dinucleotide (NADH) to the substrate increased
      the respiratory rate of slowly-respiring pollen more than that of fast-respiring
      pollen, but carbonyl cyanide 3-chlorophenylhydrazone (CCCP) and adenosine 5'
      diphosphate (ADP) had less effect. After 1-4 h incubation, the respiration rate
      of the slow- or medium-respiring pollen lots had decreased, but was stimulated by
      succinate or NADH, and to a lesser degree by ADP. By 7 h, the respiration rate of
      all pollen lots had declined and was stimulated less by substrate, ADP or CCCP.
      The oxidation of NADH by tomato pollen contrasts with the failure of other pollen
      species to utilize this substrate; moreover, a synergistic effect of NADH and
      succinate was consistently observed. We conclude that the decline in respiration
      during incubation for up to 4 h at 30 degrees C may reflect a lack of respiratory
      substrate. After 7 h, however, the decreased response to substrate indicates a
      loss of mitochondrial integrity or an accumulation of metabolic inhibitors. It is
      concluded that at 30 degrees C (a moderately high temperature for tomato pollen),
      the initially high rate of respiration leads to exhaustion of the endogenous
      respiratory substrates (particularly in pollen with low to medium respiratory
      activity), but subsequently to ageing and a loss of mitochondrial activity.

PMID- 20033435
TI  - Class B beta-expansins are needed for pollen separation and stigma penetration.
AB  - Group 1 grass pollen allergens comprise a distinctive clade within the beta
      expansin family of cell wall-loosening proteins and are divided by sequence
      divergence into two phylogenetically separable classes (A and B). They have been
      proposed to loosen the walls of the stigma and style. Supporting this idea, we
      recently showed that a transposon insertion in one of the maize group-1 allergen
      genes reduces the ability of pollen to effect fertilization under conditions of
      pollen competition. In this work, we provide additional information on the
      phenotype of this mutant, showing that pollen deficient in beta-expansin gene
      expression tended to form large aggregates, leading to poor pollen dispersal on
      anther dehiscence, and that emerging pollen tubes had difficulties entering the
      silk. In addition, a silencing construct was created to reduce expression of all
      the class B genes with results that are consistent with those seen with the
      transposon insertional line, including reduced transgene transmission through the
      pollen. Our results provide a more detailed understanding of the role of group 1
      allergens (pollen beta-expansins) in maize pollen development, pollen dispersal,
      pollen tube penetration into the style, and pollen tube growth through the
      transmitting tract.

PMID- 20033436
TI  - Description of a fertilization-independent obligate apomictic species:
      Corunastylis apostasioides Fitzg.
AB  - The Australian midge orchid Corunastylis apostasioides of the tribe Diurideae has
      completely eliminated any male contribution in the process of seed formation,
      which occurs directly from the maternal tissue by a process termed apomixis.
      Here, we report C. apostasioides to be an obligate apomictic species devoid of
      any sexuality and compare its development to a close sexual relative C. fimbriata
      (R. Br.) D.L. Jones & M.A. Clem. Apomictic characteristics in C. apostasioides
      include production of seed in absence of fertilization, frequently closed
      flowers, production of immature pollen in non-dehiscent anthers, expansion of
      ovaries despite the lack of fertilization and the absence of a citronella scent
      that is found in C. fimbriata produced to attract pollinating vinegar flies
      (Jones 2006). The nature of apomixis in C. apostasioides was examined by ovule
      histology and amplified fragment length polymorphism (AFLP) in each case drawing
      comparison with sexual C. fimbriata. In C. apostasioides the central megaspore
      mother cell undergoes diplosporic apomixis, while additional embryos are derived
      from nucellar or integument initials formed by sporophytic apomixis. Typical of
      apomicts, C. apostasioides is polyploid compared to the sexual C. fimbriata. The
      divergences of C. apostasioides from sexuality to apomictic development are
      discussed.

PMID- 20033437
TI  - LAP3, a novel plant protein required for pollen development, is essential for
      proper exine formation.
AB  - We isolated lap3-1 and lap3-2 mutants in a screen for pollen that displays
      abnormal stigma binding. Unlike wild-type pollen, lap3-1 and lap3-2 pollen exine
      is thinner, weaker, and is missing some connections between their roof-like
      tectum structures. We describe the mapping and identification of LAP3 as a novel
      gene that contains a repetitive motif found in beta-propeller enzymes. Insertion
      mutations in LAP3 lead to male sterility. To investigate possible roles for LAP3
      in pollen development, we assayed the metabolite profile of anther tissues
      containing developing pollen grains and found that the lap3-2 defect leads to a
      broad range of metabolic changes. The largest changes were seen in levels of a
      straight-chain hydrocarbon nonacosane and in naringenin chalcone, an obligate
      compound in the flavonoid biosynthesis pathway.

PMID- 20033438
TI  - A modifier locus affecting the expression of the S-RNase gene could be the cause
      of breakdown of self-incompatibility in almond.
AB  - Self-compatibility has become the primary objective of most almond (Prunus
      amygdalus Batsch) breeding programmes in order to avoid the problems related to
      the gametophytic self-incompatibility system present in almond. The progeny of
      the cross 'Vivot' (S(23)S(fa)) x 'Blanquerna' (S(8)S(fi)) was studied because
      both cultivars share the same S(f) allele but have a different phenotypic
      expression: active (S(fa)) in 'Vivot' and inactive (S(fi)) in 'Blanquerna'. In
      addition, the microscopic observation of pollen tube growth after self
      pollination over several years showed an unexpected self-incompatible behaviour
      in most seedlings of this cross. The genotypes of this progeny showed that the
      S(fi) pollen from 'Blanquerna' was not able to grow down the pistils of 'Vivot'
      harbouring the S(fa) allele, confirming the active function of this allele
      against the inactive form of the same allele, S(fi). As self-compatibility was
      observed in some S(8)S(23) and S(8)S(fa) individuals of this progeny, the S(f)
      haplotype may not always be linked to the expression and transmission of self
      compatibility in almond, suggesting that a modifier locus may be involved in the
      mechanism of self-incompatibility in plants.

PMID- 20033439
TI  - Post-pollination mechanisms in Nicotiana longiflora and N. plumbaginifolia:
      pollen tube growth rate, offspring paternity and hybridization.
AB  - In natural populations where interfertile species coexist, conspecific and
      heterospecific pollen can be delivered to the stigmas. Post-pollination
      mechanisms might determine the seed siring success of different pollen donors
      within species as well as the chances for hybridization between species.
      Nicotiana longiflora and N. plumbaginifolia occur in sympatry in Northwest
      Argentina, where they have overlapping flowering seasons and share floral
      visitors. We explored (1) pollen tube growth rates for outcross versus self
      pollen in single-donor pollinations; (2) siring success of self versus outcross
      pollen donors in competitive pollinations, and (3) possibilities for
      hybridization by performing two- (outcross conspecific vs. heterospecific) and
      three-pollen donor (self vs. outcross vs. heterospecific) crosses. In N.
      longiflora, both pollen tube growth rate and siring success favored outcross
      pollen over self pollen and strong rejection of heterospecific pollen. In N.
      plumbaginifolia, pollen tube growth rate was similar for self and outcross
      pollen, self pollen sired similar numbers of offspring than outcross pollen and
      heterospecific pollen sired roughly the same number of progeny than self pollen.
      Results suggest that in natural sympatric populations, interspecific crosses
      would likely lead to unidirectional hybridization with N. plumbaginifolia as the
      seed parent.

PMID- 20033440
TI  - The extracellular lipase EXL4 is required for efficient hydration of Arabidopsis
      pollen.
AB  - Pollination in species with dry stigmas begins with the hydration of desiccated
      pollen grains on the stigma, a highly regulated process involving the proteins
      and lipids of the pollen coat and stigma cuticle. Self-incompatible species of
      the Brassicaceae block pollen hydration, and while the early signaling steps of
      the self-incompatibility response are well studied, the precise mechanisms
      controlling pollen hydration are poorly understood. Both lipids and proteins are
      important for hydration; loss of pollen coat lipids and proteins results in
      defective or delayed hydration on the stigma surface. Here, we examine the role
      of the pollen coat protein extracellular lipase 4 (EXL4), in the initial steps of
      pollination, namely hydration on the stigma. We identify a mutant allele, exl4-1,
      that shows a reduced rate of pollen hydration. exl4-1 pollen is normal with
      respect to pollen morphology and the downstream steps in pollination, including
      pollen tube germination, growth, and fertilization of ovules. However, owing to
      the delay in hydration, exl4-1 pollen is at a disadvantage when competed with
      wild-type pollen. EXL4 also functions in combination with GRP17 to promote the
      initiation of hydration. EXL4 is similar to GDSL lipases, and we show that it
      functions in hydrolyzing ester bonds. We report a previously unknown function for
      EXL4, an abundant pollen coat protein, in promoting pollen hydration on the
      stigma. Our results indicate that changes in lipid composition at the pollen
      stigma interface, possibly mediated by EXLs, are required for efficient
      pollination in species with dry stigmas.

PMID- 20033441
TI  - Sexual plant reproduction congresses: 2008.

PMID- 20033443
TI  - Control of anther cell differentiation: a teamwork of receptor-like kinases.
AB  - Successful sexual reproduction depends on normal cell differentiation during
      early anther development in flowering plants. The anther typically has four
      lobes, each of which contains highly specialized reproductive (microsporocyte)
      and somatic cells (epidermis, endothecium, middle layer, and tapetum). To date,
      six leucine-rich repeat receptor-like protein kinases (LRR-RLK) have been
      identified to have roles in regulation of anther cell patterning in Arabidopsis
      thaliana. EXCESS MICROSPOROCYTES1 (EMS1)/EXTRA SPOROGENOUS CELLS (EXS) and
      SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES1/2 (SERK1/2) signal the
      differentiation of the tapetum. BARELY ANY MERISTEM1/2 (BAM1/2) defines anther
      somatic cell layers, including the endothecium, middle layer, and tapetum.
      Moreover, RECEPTOR-LIKE PROTEIN KINASE2 (RPK2) is required for the
      differentiation of middle layer cells. In addition to process of anther cell
      differentiation, conserved regulation of anther cell differentiation in different
      plant species, this review mainly discusses how these receptor-like kinases and
      other regulators work together to control anther cell fate determination in
      Arabidopsis.

PMID- 20033442
TI  - The contribution of cell cycle regulation to endosperm development.
AB  - Development of the seed endosperm involves several different types of coordinated
      cell cycle programs: acytokinetic mitosis, which produces a syncytium soon after
      fertilization; cellularization through the formation of modified phragmoplasts;
      cell proliferation, in which mitosis is coupled to cell division; and, in certain
      species like cereal crops, endoreduplication. Understanding the regulation of
      these programs and their transitions is challenging, but it has the potential to
      define important links between the cell cycle, cell differentiation and
      development, as well as provide tools for the manipulation of seed yield. A
      relatively large number of mutants display endosperm proliferation defects, and
      connections with known cell cycle genes are beginning to emerge. For example, it
      is becoming increasingly evident that the master cell cycle regulators, the
      cyclin-dependent kinases and retinoblastoma-related families, play key roles in
      the events leading to endosperm formation and development. Recent studies
      highlight cross-talk between pathways controlling the cell cycle and genomic
      imprinting.

PMID- 20033444
TI  - Ovule development: genetic trends and evolutionary considerations.
AB  - Much of our current understanding of ovule development in flowering pants is
      derived from genetic and molecular studies performed on Arabidopsis thaliana.
      Arabidopsis has bitegmic, anatropous ovules, representing both the most common
      and the putative ancestral state among angiosperms. These studies show that key
      genetic determinants that act to control morphogenesis during ovule development
      also play roles in vegetative organ formation, consistent with Goethe's
      "everything is a leaf" concept. Additionally, the existence of a common set of
      genetic factors that underlie laminar growth in angiosperms fits well with
      hypotheses of homology between integuments and leaves. Utilizing Arabidopsis as a
      reference, researchers are now investigating taxa with varied ovule morphologies
      to uncover common and diverged mechanisms of ovule development.

PMID- 20033445
TI  - Arabidopsis thaliana as a model for functional nectary analysis.
AB  - Nectaries and nectar have received much research attention for well over 200
      years due to their central roles in plant-pollinator interactions. Despite this,
      only a few genes have demonstrated impacts on nectary development, and none have
      been reported to mediate de novo nectar production. This scarcity of information
      is largely due to the lack of a model that combines sizeable nectaries, and high
      levels of nectar production, along with suitable genomics resources. For example,
      even though Arabidopsis thaliana has been useful for developmental studies, it
      has been largely overlooked as a model for studying nectary function due to the
      small size of its flowers. However, Arabidopsis nectaries, along with those of
      related species, are quite operational and can be used to discern molecular
      mechanisms of nectary form and function. A current understanding of the machinery
      underlying nectary function in plants is briefly presented, with emphasis placed
      on the prospects of using Arabidopsis as a model for studying these processes.

PMID- 20033446
TI  - The evolution of postpollination reproductive isolation in Costus.
AB  - Reproductive isolation is critical to the diversification of species.
      Postpollination barriers may be important in limiting gene flow between closely
      related species, but they are relatively cryptic and their evolution is poorly
      understood. Here, we review the role of postpollination reproductive isolation in
      plants, including the various stages at which it operates and the hypotheses for
      how it may evolve. We then review empirical studies in the plant genus Costus,
      evaluating documented postpollination barriers in light of these hypotheses. We
      summarize isolation due to parental style length differences and present evidence
      supporting the hypothesis that the differences are in part a by-product of
      selection on floral morphology. Additionally, we show that reduced pollen
      adhesion, germination, and tube growth contribute to reproductive isolation
      between two closely related sympatric species of Costus. Geographic variation in
      the strength of these crossing barriers supports the hypothesis that they evolved
      under reinforcement, or direct natural selection to strengthen isolation.

PMID- 20033447
TI  - Incidence and post-pollination mechanisms of nonrandom mating in Arabidopsis
      thaliana.
AB  - Compatible pollinations from many different taxa display nonrandom mating. Here
      we describe a system for examining questions of nonrandom mating in Arabidopsis
      thaliana. Using this system, we demonstrate that Arabidopsis thaliana displays
      nonrandom mating between distinct accessions. Statistical analysis of these data
      demonstrates aspects of both pollen competition and male-female complementarity
      in these matings. Cytological experiments implicate pollen germination and pollen
      tube growth rates as possible causal factors in these nonrandom mating
      efficiencies.

PMID- 20033448
TI  - Ectopic expression of S-RNase of Petunia inflata in pollen results in its
      sequestration and non-cytotoxic function.
AB  - The specificity of S-RNase-based self-incompatibility (SI) is controlled by two S
      locus genes, the pistil S-RNase gene and the pollen S-locus-F-box gene. S-RNase
      is synthesized in the transmitting cell; its signal peptide is cleaved off during
      secretion into the transmitting tract; and the mature "S-RNase", the subject of
      this study, is taken up by growing pollen tubes via an as-yet unknown mechanism.
      Upon uptake, S-RNase is sequestered in a vacuolar compartment in both non-self
      (compatible) and self (incompatible) pollen tubes, and the subsequent disruption
      of this compartment in incompatible pollen tubes correlates with the onset of the
      SI response. How the S-RNase-containing compartment is specifically disrupted in
      incompatible pollen tubes, however, is unknown. Here, we circumvented the uptake
      step of S-RNase by directly expressing S(2)-RNase, S(3)-RNase and non
      glycosylated S(3)-RNase of Petunia inflata, with green fluorescent protein (GFP)
      fused at the C-terminus of each protein, in self (incompatible) and non-self
      (compatible) pollen of transgenic plants. We found that none of these ectopically
      expressed S-RNases affected the viability or the SI behavior of their self or non
      self-pollen/pollen tubes. Based on GFP fluorescence of in vitro-germinated pollen
      tubes, all were sequestered in both self and non-self-pollen tubes. Moreover, the
      S-RNase-containing compartment was dynamic in living pollen tubes, with movement
      dependent on the actin-myosin-based molecular motor system. All these results
      suggest that glycosylation is not required for sequestration of S-RNase expressed
      in pollen tubes, and that the cytosol of pollen is the site of the cytotoxic
      action of S-RNase in SI.

PMID- 20033449
TI  - Effects of APETALA2 on embryo, endosperm, and seed coat development determine
      seed size in Arabidopsis.
AB  - Arabidopsis APETALA2 (AP2) controls seed mass maternally, with ap2 mutants
      producing larger seeds than wild type. Here, we show that AP2 influences
      development of the three major seed compartments: embryo, endosperm, and seed
      coat. AP2 appears to have a significant effect on endosperm development. ap2
      mutant seeds undergo an extended period of rapid endosperm growth early in
      development relative to wild type. This early expanded growth period in ap2 seeds
      is associated with delayed endosperm cellularization and overgrowth of the
      endosperm central vacuole. The subsequent period of moderate endosperm growth is
      also extended in ap2 seeds largely due to persistent cell divisions at the
      endosperm periphery. The effect of AP2 on endosperm development is mediated by
      different mechanisms than parent-of-origin effects on seed size observed in
      interploidy crosses. Seed coat development is affected; integument cells of ap2
      mutants are more elongated than wild type. We conclude that endosperm overgrowth
      and/or integument cell elongation create a larger postfertilization embryo sac
      into which the ap2 embryo can grow. Morphological development of the embryo is
      initially delayed in ap2 compared with wild-type seeds, but ap2 embryos become
      larger than wild type after the bent-cotyledon stage of development. ap2 embryos
      are able to fill the enlarged postfertilization embryo sac, because they undergo
      extended periods of cell proliferation and seed filling. We discuss potential
      mechanisms by which maternally acting AP2 influences development of the zygotic
      embryo and endosperm to repress seed size.

PMID- 20033450
TI  - Epigenetic marks in the mature pollen of Quercus suber L. (Fagaceae).
AB  - We have analysed the distribution of epigenetic marks for histone modifications
      at lysine residues H3 and H4, and DNA methylation, in the nuclei of mature pollen
      cells of the Angiosperm tree Quercus suber; a monoecious wind pollinated species
      with a protandrous system, and a long post-pollination period. The ultrasonic
      treatment developed for the isolation of pollen nuclei proved to be a fast and
      reliable method, preventing the interference of cell wall autofluorescence in the
      in situ immunolabelling assays. In contrast with previous studies on herbaceous
      species with short progamic phases, our results are consistent with a high level
      of silent (5-mC and H3K9me2) epigenetic marks on chromatin of the generative
      nucleus, and the prevalence of active marks (H3K9me3 and H4Kac) in the vegetative
      nucleus. The findings are discussed in terms of the pollination/fertilization
      timing strategy adopted by this plant species.

PMID- 20033451
TI  - Mechanism of action of nitrous oxide gas applied as a polyploidizing agent during
      meiosis in lilies.
AB  - Nitrous oxide gas (N(2)O) can be used to produce polyploid plants, but the
      mechanism of action is unknown. The actin and microtubule cytoskeleton was
      observed in N(2)O-treated microsporocytes of Lilium spp 'Asiatic hybrid lilies'
      using fluorescence microscopy after staining with DAPI, FITC-conjugated tubulin
      antibody, and phalloidin-conjugated Alexa Fluor 546. Additionally,
      microsporocytes of L. longiflorum were observed with acetocarmine staining
      following N(2)O treatment. A typical metaphase I microtubule distribution was
      observed in control microsporocytes. After treatment with N(2)O for 24 h,
      microtubules were effectively depolymerized; this prevented chromosomes from
      moving to the poles, resulting in chromosome retention in the center of N(2)O
      treated cells. Cell plate formation took place without delay, however, yielding
      one daughter cell with a diploid genome and another daughter without chromosomes.
      In addition, N(2)O treatment often induced micronuclei due to aberrant chromosome
      separation during cytokinesis. Actin filaments in microsporocytes are insensitive
      to N(2)O. These findings indicate that N(2)O mediates polyploidization by
      inhibiting microtubule polymerization, but not actin filament formation, during
      microsporocyte meiosis.

PMID- 20033452
TI  - Histological comparison between wheat embryos developing in vitro from isolated
      zygotes and those developing in vivo.
AB  - There is currently great interest shown in understanding the process of
      embryogenesis and, due to the relative inaccessibility of these structures in
      planta, extended studies are carried out in various in vitro systems. The culture
      of isolated zygotes in particular provides an excellent platform to study the
      process of in planta embryogenesis. However, very few comparisons have been made
      between zygotic embryos grown entirely in cultures and those grown in vivo. The
      present study analyses the differences and similarities between the in vitro and
      in vivo development of wheat zygotic embryos at the level of morphology and
      histology. The study was possible thanks to an efficient culture system and an
      appropriate method of preparing isolated wheat zygotes for microscopy. The in
      vitro embryos were fixed, embedded and sectioned in the two-celled, globular,
      club-shaped and fully differentiated stages. Embryos developing in vitro closely
      followed the morphology of their in planta counterparts and their cell types and
      tissues were also similar, demonstrating the applicability of the present culture
      system for studying the process of zygotic embryogenesis. However, some important
      differences were also detected in the case of in vitro development: the
      disturbance of or lack of initial polarity led to changes in the division
      symmetry of the zygotes and subsequently to the formation of uniform cells in the
      globular structures. Presumably, differences between the in vitro and in planta
      environments resulted in a lower level of differentiation and maturation in in
      vitro embryos and in abundant starch and protein accumulation in the scutellum.

PMID- 20033453
TI  - Diploid endosperm formation in Tulipa spp. and identification of a 1:1 maternal
      to-paternal genome ratio in endosperms of T. gesneriana L.
AB  - Most Liliaceae plants have the tetrasporic Fritillaria-type embryo sac and
      normally form diploid embryos and pentaploid endosperms derived from a 4:1
      maternal-to-paternal genome ratio (4m:1p) after double fertilization. Here we
      characterize embryo sac and endosperm formation in Tulipa spp. of Liliaceae.
      Chromosome analysis using seeds derived from 2x x 2x crosses of Tulipa gesneriana
      (2n = 2x = 24) identified diploid chromosome number in the endosperm. Similarly,
      flow cytometric analysis confirmed diploid endosperm formation in T. gesneriana,
      T. fosteriana (2n = 2x = 24) and T. greigii (2n = 2x = 24). To further study the
      possible mechanism of diploid endosperm formation, we made interploidy crosses of
      triploid (2n = 3x = 36) x diploid in which aneuploid seeds with various
      chromosome numbers (2n = 25-36) were produced. Again, flow cytometric analysis
      confirmed the same ploidy level in both embryos and endosperms at all aneuploidy
      levels, suggesting that only a single haploid polar nucleus contributes to
      endosperm formation at fertilization. Histological observation further confirmed
      the physical separation of two polar nuclei by a large vacuole in the Fritillaria
      type embryo sac of T. gesneriana that appeared to prevent the fusion of the two
      polar nuclei that originated at the micropylar and chalazal ends before
      fertilization. Taken together, these results indicate that diploid endosperms
      (1m:1p) are normally formed in Tulipa spp. by fusion of the micropylar polar
      nucleus (n) and a spermatid (n) but not by normal triple fusion. We also show
      that tulip endosperm partially overcomes the triploid block mechanism that occurs
      in interploidy crosses. Based on these observations, the possible role of triple
      nuclear fusion in double fertilization is discussed.

PMID- 20033454
TI  - The relationship of the female reproductive success of Eucalyptus globulus to the
      endogenous properties of the flower.
AB  - Low capsule and seed set is a major factor limiting seed production in Eucalyptus
      globulus seed orchards. Controlled pollination studies showed that the
      reproductive success (number of seeds produced per flower pollinated) was
      primarily determined by the female. We aimed to identify the factors contributing
      to the differences in reproductive success between female genotypes in terms of
      the physical and anatomical properties of the flower. We studied pairs of
      genotypes of high and low reproductive success from each of three races (Furneaux
      Group, Strzelecki Ranges and Western Otways) growing in a seed orchard.
      Controlled pollinations were performed on six females and along with flower
      physical measurements, pollen tube growth and seed set were assessed. Overall
      tree reproductive success was positively correlated with flower size, ovule
      numbers, style size, cross-sectional area of conductive tissue within the style
      (all of which were inter-correlated) and the proportion of pollen tubes reaching
      the bottom of the style. Significant positive correlations of reproductive
      success and flower physical properties between different ramets of the same
      genotypes across seasons suggests a genetic basis to the variation observed. The
      majority of pollen tube attrition occurred within the first millimetre of the cut
      style and appeared to be associated with differences in style physiology. When
      examined as pairs within races the difference in reproductive success for the
      Western Otways pair was simply explained by differences in flower size and the
      number of ovules per flower. Physical features did not differ significantly for
      the Strzelecki Ranges pair, but the proportion of pollen tubes reaching the
      bottom of the style was lower in the less reproductively successful genotype,
      suggesting an endogenous physiological constraint to pollen tube growth. The
      difference in reproductive success between the females from the Furneaux Group
      was associated with a combination of these factors.

PMID- 20033455
TI  - Primary trisomics obtained from autotriploid by diploid reciprocal crosses in
      cucumber.
AB  - To promote cytogenetical studies on cucumber (Cucumis sativus L., 2n = 2x = 14),
      the reciprocal crosses were made between autotriploid and diploid for selecting
      the primary trisomics. Meanwhile, chromosome behavior during meiosis in
      autotriploid cucumber was investigated to look for cytological evidences for
      origin of primary trisomics. Many viable F(1) seeds were obtained from reciprocal
      crosses between autotriploid and diploid. The number of chromosomes of 56
      surviving progenies varied from 14 to 28, with plants having 2n = 15 occurring at
      the highest frequency (51.8%). Primary trisomics were firstly obtained in this
      study. Four types of primary trisomics were isolated and they could be
      distinguished from each other, as well as diploid. Variable chromosome
      configurations, e.g. univalent, bivalents and trivalents were observed in many
      pollen mother cells of the autotriploid at metaphase I. Binomial chromosome
      distribution was observed at anaphase I and frequency of 8/13 was 6.25%. The
      meiosis of autotriploid, especially the class of gametes with eight chromosomes,
      gave the cytological evidence of producing 2x + 1 type gamete and could be
      induced into primary trisomic plants from progeny of autotriploid-diploid
      crosses. These studies have established a ground work for selecting a series of
      primary trisomics, and further using them for associating linkage groups with
      specific chromosomes in cucumber.

PMID- 20033456
TI  - Cyclic pollen production in Cedrus deodara.
AB  - Based on a seven-year study of pollen production and release in two different
      natural populations of Cedrus deodara from Garhwal Himalaya, India, we determined
      that pollen output follows a two-year cycle. Pollen productivity determinations
      considered various sources of variability, including the number of pollen
      strobili per branch, strobili per tree, microsporophylls per tree and pollen
      grains per tree. Each of these parameters revealed significant year-to-year and
      population effects. Microsporangium dehiscence took from 2.5 to 3.5 days. Maximum
      dehiscence was observed between 12:00 and 14:00 h, which coincides with diurnal
      highest temperature and lowest relative humidity. Annual production of pollen per
      tree varied from averages of 4.7 x 10(9), 7.2 x 10(9) and 5.1 x 10(9) in years of
      low production, with alternate high years, producing 12.6 x 10(9), 14.1 x 10(9),
      13.3 x 10(9) and 14.0 x 10(9) pollen grains per tree. Annual pollen production in
      individual trees of C. deodara ranged from 1.4 x 10(9) to 22.3 x 10(9).

PMID- 20033457
TI  - The effect of sheltered load on reproduction in Solanum carolinense, a species
      with variable self-incompatibility.
AB  - In previous studies, we have investigated the strength of self-incompatibility
      (SI) in Solanum carolinense, a highly successful weed with a fully functional SI
      system that inhabits early successional and other disturbed habitats. We have
      found that the SI response in S. carolinense is a plastic trait-its strength
      being affected by the age of the flowers, and the presence of developing fruits
      and that there are genetic differences among families in their self-fertility.
      However, in species with a fully functional SI response, selfing would not be
      that common. As a result, deleterious recessives scattered though the genome of
      horsenettle are only occasionally exposed to selection. It has been suggested
      that deleterious recessives accumulate near S-alleles in strong SI species
      because the S-locus is located in a non-recombining region of the genome and
      because strong S-alleles are never in the homozygous state, thus sheltering some
      of the genetic load near the S-locus from selection. We performed a series of
      laboratory and greenhouse experiments to determine the extent to which sheltered
      load adds to the overall magnitude of inbreeding depression in horsenettle.
      Specifically, we amplified and sequenced the S-alleles from 16 genets collected
      from a large population in Pennsylvania and performed a series of controlled self
      pollinations. We then grew the selfed progeny in the greenhouse; recorded various
      measures of growth and reproductive output; and amplified and sequenced their S
      allele(s). We found that the heterozygous progeny of self-pollinations produce
      more flowers and have a greater ability to set both self and cross seed than S
      homozygous progeny. We also found evidence of variation in the magnitude of load
      among S-alleles. These results suggest that sheltered load might slow the
      fixation of weak (partially compatible) S-alleles in this population, thus adding
      to the maintenance of a mixed mating system rather than leading to the fixation
      of the selfing alleles.

PMID- 20033458
TI  - Floral biology of Ziziphus mauritiana (Rhamnaceae).
AB  - Floral development of the synchronous dichogamous species Ziziphus mauritiana, as
      followed by light and scanning electron microscopy (SEM), was divided into 11
      stages using a series of landmark events. Main cellular events happen
      synchronously in the female and the male structures, such as meiosis in micro-
      and macrosporocyte cells, tetrad microspore formation and appearance of the
      functional megaspore cell, and onset of embryo sac differentiation coinciding
      with mitosis in the microspores. The last stage was characterized by anthesis and
      continued development of the flower, beginning with anther dehiscence (male
      phase) and proceeding to the female phase, which was characterized by style
      elongation. Flowers exhibit synchronous protandrous dichogamy; anthesis takes
      place in the morning (group A, e.g., clone Q-29) and afternoon (group B, e.g.,
      clone B5/4). Stigma receptivity started after the male phase and occurred
      synchronously and complementarily with pollen dispersal in the two clones. Pollen
      viability and production were similar in the two clones, but the pollen diameter
      of Q-29 was significantly larger than that of B5/4. This study provides the basis
      for understanding the biological mechanisms regulating floral development, thus
      expanding the prospects for Z. mauritiana breeding programs and for further
      molecular and genetic studies of this species.

PMID- 20033459
TI  - Distribution of calcium in the stigma and style of tobacco during pollen
      germination and tube elongation.
AB  - Potassium antimonate was used to locate loosely bound calcium in the stigma and
      style of tobacco. The tobacco stigma is wet and covered by a thick layer of
      glycoprotein exudate at anthesis. The exudate contains abundant vesicles, which
      are densely labeled with calcium precipitates. When pollen grains arrive at the
      stigma, become hydrated, and as the pollen swells, Ca(2+) precipitates accumulate
      at the aperture. Calcium precipitates that accumulate in pollen cytoplasm are
      initially concentrated within small vacuoles, but as germination proceeds these
      appear to fuse, forming prominent, densely labeled vesicles that preferentially
      accumulate near the proximal region of the growing tube. Although the stigma has
      abundant particles, few calcium precipitates are observed in the transmitting
      tissue from anthesis to 11 h after pollination. However, at 22 h after
      pollination, accumulation of calcium increases distally from the stigmatic
      interface with the transmitting tissue through the length of the style to the
      ovary. An examination of flowering plants with differing floral biology will be
      needed to understand the role of loosely bound calcium accumulation and its
      relationship to tissue-level changes in calcium uptake, maintenance of other
      calcium pools, including [Ca(2+)](cyt), and in pollen and style maturation during
      the progamic phase.

PMID- 20033460
TI  - Isolation of genes from female sterile flowers in Medicago sativa.
AB  - A better knowledge of female sporogenesis and gametogenesis could have several
      practical applications, from commercial hybrid seed production to gene
      containment in GM crops. With the purpose of isolating genes involved in the
      megasporogenesis process, the cDNA-AFLP technique was employed to isolate
      transcript-derived fragments (TDF) differentially expressed between female
      fertile and female-sterile full-sib alfalfa plants. This female sterility trait
      involves female-specific arrest of sporogenesis at early prophase associated with
      ectopic, massive callose deposition within the nucellus. Ninety-six TDFs were
      generated and BLAST analyses revealed similarities with genes involved in
      different Gene Ontology categories. Three TDFs were selected based on their
      putative functions: showing high similarity to a soybean flower-expressed beta
      1,3-glucanase, to an Arabidopsis thaliana MAPKKK, and to an A. thaliana
      eukaryotic initiation translation factor eIF4G III, respectively. The full length
      mRNA sequences were obtained. RT-PCR and in situ hybridizations were performed to
      confirm differential expression during flower development. The genomic
      organization of the three genes was assessed through sequencing and Southern
      experiments. Sequence polymorphisms were found between sterile and fertile
      plants. Our approach based on differential display and bulked segregant analysis
      was successful in isolating genes that were differentially expressed between
      fertile and sterile alfalfa plants.

PMID- 20033461
TI  - Quantitative assessment of myelopathy patients using motor evoked potentials
      produced by transcranial magnetic stimulation.
AB  - Motor evoked potentials (MEPs) study using transcranial magnetic stimulation
      (TMS) may give a functional assessment of corticospinal conduction. But there are
      no large studies on MEPs using TMS in myelopathy patients. The purpose of this
      study is to confirm the usefulness of MEPs for the assessment of the myelopathy
      and to investigate the use of MEPs using TMS as a screening tool for myelopathy.
      We measured the MEPs of 831 patients with symptoms and signs suggestive of
      myelopathy using TMS. The MEPs from the abductor digiti minimi (ADM) and abductor
      hallucis (AH) muscles were evoked by transcranial magnetic brain stimulation.
      Central motor conduction time (CMCT) is calculated by subtracting the peripheral
      conduction time from the MEP latency. Later, 349 patients had surgery for
      myelopathy (operative group) and 482 patients were treated conservatively
      (nonoperative group). CMCTs in the operative group and nonoperative group were
      assessed. MEPs were prolonged in 711 patients (86%) and CMCTs were prolonged in
      493 patients (59%) compared with the control patients. CMCTs from the ADM and AH
      in the operative group were significantly more prolonged than that in the
      nonoperative group. All patients in the operative group showed prolongation of
      MEPs or CMCTs or multiphase of the MEP wave. MEP abnormalities are useful for an
      electrophysiological evaluation of myelopathy patients. Moreover, MEPs may be
      effective parameters in spinal pathology for deciding the operative treatment.

PMID- 20033462
TI  - Motor cortical hyperexcitability in idiopathic scoliosis: could focal dystonia be
      a subclinical etiological factor?
AB  - The aetiology of idiopathic scoliosis (IS) remains unknown; however, there is a
      growing body of evidence suggesting that the spine deformity could be the
      expression of a subclinical nervous system disorder. A defective sensory input or
      an anomalous sensorimotor integration may lead to an abnormal postural tone and
      therefore the development of a spine deformity. Inhibition of the motor cortico
      cortical excitability is abnormal in dystonia. Therefore, the study of cortico
      cortical inhibition may shed some insight into the dystonia hypothesis regarding
      the pathophysiology of IS. Paired pulse transcranial magnetic stimulation was
      used to study cortico-cortical inhibition and facilitation in nine adolescents
      with IS, five teenagers with congenital scoliosis (CS) and eight healthy age
      matched controls. The effect of a previous conditioning stimulus (80% intensity
      of resting motor threshold) on the amplitude of the motor-evoked potential
      induced by the test stimulus (120% of resting motor threshold) was examined at
      various interstimulus intervals (ISIs) in both abductor pollicis brevis muscles.
      The results of healthy adolescents and those with CS showed a marked inhibitory
      effect of the conditioning stimulus on the response to the test stimulus at
      interstimulus intervals shorter than 6 ms. These findings do not differ from
      those reported for normal adults. However, children with IS revealed an
      abnormally reduced cortico-cortical inhibition at the short ISIs. Cortico
      cortical inhibition was practically normal on the side of the scoliotic convexity
      while it was significantly reduced on the side of the scoliotic concavity. In
      conclusion, these findings support the hypothesis that a dystonic dysfunction
      underlies in IS. Asymmetrical cortical hyperexcitability may play an important
      role in the pathogenesis of IS and represents an objective neurophysiological
      finding that could be used clinically.

PMID- 20033463
TI  - Active reassortment of H9 influenza viruses between wild birds and live-poultry
      markets in Korea.
AB  - Surveillance of H9 avian influenza viruses in Korean live-poultry markets from
      September 2004 through October 2007 was carried out to investigate active
      reassortment between wild migratory birds and domestic poultry in Korea.
      Antigenic and phylogenetic analyses showed that most of the isolates belong to
      the previous Korean H9N2-like lineage and differ from the southeastern Chinese
      strains. Interestingly, the Ck/Korea/LPM77/06 group (genotype B) and
      Dk/Korea/LPM248/07 group (genotype C) showed unique properties distinct from
      those of other Korean H9N2 strains. Although the HA genes of these two groups
      belong to Korean H9N2-like lineage, the PA genes closely resemble those of the
      Chinese Y280-like lineage. In addition, the PB2 genes of the Dk/Korea/LPM248/07
      group were closely related to those isolated from migratory birds. Several other
      isolates also clustered within the H9N2 B genotype, an indication that there are
      at least two predominant H9N2 influenza genotypes in Korea. Another isolate,
      Dk/Korea/LPM71/06, was identified as an H9N1 subtype, the first ever discovered
      in Korean live-poultry markets. These findings reveal that reassortment of Korean
      H9 influenza viruses has occurred frequently in live-poultry markets and may have
      been mediated by introduction of genetic material from viruses circulating among
      migratory wild birds to domestic birds. Consequently, the new dominant H9N2
      genotypes have become established in Korean live-poultry markets through
      continued reassortment.

PMID- 20033464
TI  - Homology modeling and molecular dynamics simulations of HgiDII methyltransferase
      in complex with DNA and S-adenosyl-methionine: catalytic mechanism and
      interactions with DNA.
AB  - M.HgiDII is a methyltransferase (MTase) from Herpetosiphon giganteus that
      recognizes the sequence GTCGAC. This enzyme belongs to a group of MTases that
      share a high degree of amino acid similarity, albeit none of them has been
      thoroughly characterized. To study the catalytic mechanism of M.HgiDII and its
      interactions with DNA, we performed molecular dynamics simulations with a
      homology model of M.HgiDII complexed with DNA and S-adenosyl-methionine. Our
      results indicate that M.HgiDII may not rely only on Glu119 to activate the
      cytosine ring, which is an early step in the catalysis of cytosine methylation;
      apparently, Arg160 and Arg162 may also participate in the activation by
      interacting with cytosine O2. Another residue from the catalytic site, Val118,
      also played a relevant role in the catalysis of M.HgiDII. Val118 interacted with
      the target cytosine and kept water molecules from accessing the region of the
      catalytic pocket where Cys79 interacts with cytosine, thus preventing water
      mediated disruption of interactions in the catalytic site. Specific recognition
      of DNA was mediated mainly by amino acids of the target recognition domain,
      although some amino acids (loop 80-88) of the catalytic domain may also
      contribute to DNA recognition. These interactions involved direct contacts
      between M.HgiDII and DNA, as well as indirect contacts through water bridges.
      Additionally, analysis of sequence alignments with closely related MTases helped
      us to identify a motif in the TRD of M.HgiDII that may be relevant to specific
      DNA recognition.

PMID- 20033465
TI  - Safety and immunogenicity of an investigational quadrivalent meningococcal
      conjugate vaccine after one or two doses given to infants and toddlers.
AB  - With the emergence of multiple meningococcal serogroups in different geographic
      areas, broad vaccine protection from infancy is desirable. One hundred and
      seventy-five infants received either two doses of a meningococcal quadrivalent
      (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of
      MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months.
      Bactericidal antibody titers using human complement were measured before and 1
      month after each dose. Injection-site reactions were reported by 22-45% of
      participants following MenACWY-CRM given at 6 or 12 months. Similar proportions
      of subjects had injection-site reactions following two doses of MenACWY-CRM (32
      41%) or one dose of MenC (26-44%). The incidence of systemic adverse events was
      comparable between groups. After two doses of MenACWY-CRM, the percentages of
      participants reporting hSBA titers >or=8 were 100% for C, W-135, and Y, and 84%
      for A. Serogroup C titers were more than 10-fold higher after two doses of
      MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C
      titers were comparable following a single dose of MenACWY-CRM or MenC at 12
      months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two
      doses at 6 and 12 months of age.

PMID- 20033467
TI  - Carbon dynamics and budget in a Zoysia japonica grassland, central Japan.
AB  - The ecosystem carbon budget was estimated in a Japanese Zoysia japonica
      grassland. The green biomass started to grow in May and peaked from mid-July to
      September. Seasonal variations in soil CO(2) flux and root respiration were
      mediated by changes in soil temperature. Annual soil CO(2) flux was 1,121.4 and
      1,213.6 g C m(-2) and root respiration was 471.0 and 544.3 g C m(-2) in 2007 and
      2008, respectively. The root respiration contribution to soil CO(2) flux ranged
      from 33% to 71%. During the growing season, net primary production (NPP) was
      747.5 and 770.1 g C m(-2) in 2007 and 2008, respectively. The biomass removed by
      livestock grazing (GL) was 122.1 and 102.7 g C m(-2), and the livestock returned
      28.2 and 25.6 g C m(-2) as fecal input (FI) in 2007 and 2008, respectively. The
      decomposition of FI (DL, the dry weight loss due to decomposition) was very low,
      1.5 and 1.4 g C m(-2), in 2007 and 2008. Based on the values of annual NPP, soil
      CO(2) flux, root respiration, GL, FI, and DL, the estimated carbon budget of the
      grassland was 1.7 and 22.3 g C m(-2) in 2007 and 2008, respectively. Thus, the
      carbon budget of this Z. japonica grassland ecosystem remained in equilibrium
      with the atmosphere under current grazing conditions over the 2 years of the
      study.

PMID- 20033468
TI  - Carbon cycling and net ecosystem production at an early stage of secondary
      succession in an abandoned coppice forest.
AB  - Secondary mixed forests are one of the dominant forest cover types in human
      dominated temperate regions. However, our understanding of how secondary
      succession affects carbon cycling and carbon sequestration in these ecosystems is
      limited. We studied carbon cycling and net ecosystem production (NEP) over 4
      years (2004-2008) in a cool-temperate deciduous forest at an early stage of
      secondary succession (18 years after clear-cutting). Net primary production of
      the 18-year-old forest in this study was 5.2 tC ha(-1 )year(-1), including below
      ground coarse roots; this was partitioned into 2.5 tC ha(-1 )year(-1) biomass
      increment, 1.6 tC ha(-1 )year(-1) foliage litter, and 1.0 tC ha(-1 )year(-1)
      other woody detritus. The total amount of annual soil surface CO(2) efflux was
      6.8 tC ha(-1 )year(-1), which included root respiration (1.9 tC ha(-1 )year(-1))
      and heterotrophic respiration (RH) from soils (4.9 tC ha(-1 )year(-1)). The 18
      year forest at this study site exhibited a great increase in biomass pool as a
      result of considerable total tree growth and low mortality of tree stems. In
      contrast, the soil organic matter (SOM) pool decreased markedly (-1.6 tC ha(-1
      )year(-1)), although further study of below-ground detritus production and RH of
      SOM decomposition is needed. This young 18-year forest was a weak carbon sink
      (0.9 tC ha(-1 )year(-1)) at this stage of secondary succession. The NEP of this
      18-year forest is likely to increase gradually because biomass increases with
      tree growth and with the improvement of the SOM pool through increasing litter
      and dead wood production with stand development.

PMID- 20033469
TI  - Comparison of different mixed cultures for bio-hydrogen production from ground
      wheat starch by combined dark and light fermentation.
AB  - Composition of the mixed culture was varied in combined dark-light fermentation
      of wheat powder starch in order to improve hydrogen gas formation rate and yield.
      Heat-treated anaerobic sludge and pure culture of Clostridium beijerinckii (DSMZ
      791T) were combined with two different light fermentation bacteria of Rhodobacter
      sphaeroides (RS-NRRL and RS-RV) in order to select a more suitable mixture
      resulting in high hydrogen yield and formation rate. A combination of the
      anaerobic sludge and RS-NRRL yielded the highest cumulative hydrogen (CHF = 140
      ml), the highest yield (0.36 mol H2 mol(-1) glucose) and specific hydrogen
      formation rate (2.5 ml H2 g(-1) biomass h(-1)). During dark fermentation (70 h)
      hydrogen was produced simultaneously by the dark and light fermentation bacteria
      using glucose from hydrolyzed starch. However, only light fermentation bacteria
      produced hydrogen from VFA's derived from dark fermentation after a long
      adaptation period.

PMID- 20033470
TI  - Fermentative production of self-toxic fungal secondary metabolites.
AB  - Fungi are well known for their vast diversity of secondary metabolites that
      include many life-saving drugs and highly toxic mycotoxins. In general, fungal
      cultures producing such metabolites are immune to their toxic effects. However,
      some are known to produce self-toxic compounds that can pose production
      optimization challenges if the metabolites are needed in large amounts for
      chemical modification. One such culture, LV-2841, was identified as the lead for
      one of our exploratory projects. This culture was found to be a slow grower that
      produced trace amounts of a known metabolite, cercosporamide, under the standard
      flask fermentation conditions, and extensive medium optimization studies failed
      to yield higher titers. Poor growth of the culture in liquid media was attributed
      to the self-toxicity of cercosporamide to the producing organism, and the minimum
      inhibitory concentration (MIC) of cercosporamide was estimated to be in the range
      of 8-16 microg/ml. Fermentations carried out in media containing Diaion HP20
      resin afforded significantly higher titers of the desired compound. While several
      examples of resin-based fermentations of soil streptomyces have been published,
      this approach has rarely been used for fungal fermentations. Over a 100-fold
      increase in the production titer of cercosporamide, a self-toxic secondary
      metabolite, was achieved by supplementing the production medium with a
      commercially available neutral adsorbent resin.

PMID- 20033471
TI  - Transcranial electro-hyperthermia combined with alkylating chemotherapy in
      patients with relapsed high-grade gliomas: phase I clinical results.
AB  - Non-invasive loco-regional electro-hyperthermia (EHT) plus alkylating
      chemotherapy is occasionally used as salvage treatment in the relapse of patients
      with high-grade gliomas. Experimental data and retrospective studies suggest
      potential effects. However, no prospective clinical results are available. We
      performed a single-center prospective non-controlled single-arm Phase I trial.
      Main inclusion criteria were recurrent high-grade glioma WHO Grade III or IV, age
      18-70, and Karnofsky performance score > or = 70. Primary endpoints were dose
      limiting toxicities (DLT) and maximum tolerated dose (MTD) with the combined
      regimen. Groups of 3 or 4 patients were treated 2-5 times a week in a dose
      escalation scheme with EHT. Alkylating chemotherapy (ACNU, nimustin) was
      administered at a dose of 90 mg/m(2) on day 1 of 42 days for up to six cycles or
      until tumor progression (PD) or DLT occurred. Fifteen patients with high-grade
      gliomas were included. Relevant toxicities were local pain and increased focal
      neurological signs or intracranial pressure. No DLT occurred. In some patients,
      the administration of mannitol during EHT or long-term use of corticosteroids was
      necessary to resolve symptoms. Although some patients showed responses in their
      primarily treated sites, the pattern of response was not well defined. EHT plus
      alkylating chemotherapy is tolerable in patients with relapse of high-grade
      gliomas. Episodes of intracranial pressure were, at least, possibly attributed to
      EHT but did not cause DLTs. A Phase II trial targeting treatment effects is
      warranted on the basis of the results raised in this trial.

PMID- 20033472
TI  - Suppression of tumor suppressor Tsc2 and DNA repair glycosylase Nth1 during
      spontaneous liver tumorigenesis in Long-Evans Cinnamon rats.
AB  - Chronic inflammation and oxidative stress are arguably associated with an
      increased risk of cancer. Certain diseases that are characterized by oxyradical
      overload, such as Wilson's disease (WD), have also been associated with a higher
      risk of liver cancer. The Long-Evans Cinnamon (LEC) rat, an animal model for WD,
      is genetically predisposed to the spontaneous development of liver cancer and has
      been shown to be very useful for studying the mechanisms of inflammation-mediated
      spontaneous carcinogenesis. Endonuclease III (Nth1) plays a significant role in
      the removal of oxidative DNA damage. Nth1 and a tumor suppressor gene Tuberous
      sclerosis 2 (Tsc2) are bi-directionally regulated in humans, mice, and rats by a
      common minimal promoter containing two Ets-binding sites (EBSs). In this study,
      we examined the expression of Nth1 and Tsc2 genes during disease progression in
      the LEC rat liver. During the period of acute hepatitis (16-17 weeks), we
      observed decreased Nth1 and Tsc2 mRNA levels and a continued decrease of the Tsc2
      gene in 24 weeks in LEC rats, while the effect was minimal in Long-Evans Agouti
      (LEA) rats. This reduction in the mRNA levels was due to the reduced binding of
      EBSs in the Nth1/Tsc2 promoter. Increase in protein oxidation (carbonyl content)
      during the same time period (16-24 weeks) may have an effect on the promoter
      binding of regulatory proteins and consequent decrease in Nth1 and Tsc2 gene
      expressions during tumorigenesis.

PMID- 20033473
TI  - Cartilage oligomeric matrix protein promotes cell attachment via two independent
      mechanisms involving CD47 and alphaVbeta3 integrin.
AB  - Cartilage oligomeric matrix protein (COMP) is a pentameric approximately 524 kDa
      multidomain extracellular matrix protein and is the fifth member of the
      thrombospondin family. COMP is abundantly expressed in proliferating and
      hypertrophic chondrocytes of the growth plate, articular cartilage, synovium,
      tendon, and ligament. The spatial localization of COMP highlights its importance
      in the phenotypes of pseudoachondroplasia (PSACH) and multiple epiphyseal
      dysplasia (MED), COMP disorders that are characterized by disproportionate short
      stature, brachydactyly, scoliosis, early-onset osteoarthritis, and joint
      hypermobility. In this study, the role of COMP in ligament was investigated with
      a series of cell attachment assays using ligament cells binding to COMP. A dose
      dependent cell attachment activity was found, which was inhibited by a peptide
      containing the SFYVVMWK amino acid sequence derived from the globular C-terminal
      domain of COMP. This activity was independent of the recently described RGD
      dependent attachment activity. Function-blocking antibodies to CD47 and
      alphaVbeta3 integrin reduced cell attachment to COMP, implicating the
      participation of these cell surface molecules in COMP cell binding.
      Immunofluorescence studies showed that cell attachment to COMP induced the
      formation of lamellae containing F-actin microspikes associated with fascin. We
      propose that COMP promotes cell attachment via two independent mechanisms
      involving cell surface CD47 and alphaVbeta3 integrin and that a consequence of
      cell attachment to COMP is the specific induction of fascin-stabilized actin
      microspikes.

PMID- 20033474
TI  - Improved lysozyme stability and release properties of poly(lactide-co-glycolide)
      implants prepared by hot-melt extrusion.
AB  - PURPOSE: To assess the feasibility of hot-melt extrusion (HME) for preparing
      implants based on protein/poly(lactide-co-glycolide) (PLGA) formulations with
      special emphasis on protein stability, burst release and release completeness.
      METHOD: Model protein (lysozyme)-loaded PLGA implants were prepared with a screw
      extruder and a self-built syringe-die device as a rapid screening tool for HME
      formulation optimization. Lysozyme stability was determined using DSC, FTIR, HPLC
      and biological activity. The simultaneous effect of lysozyme and PEG loadings was
      investigated to obtain optimized formulations with high drug loading but low
      initial release. RESULTS: Lysozyme was recovered from implants with full
      biological activity after HME. The release from all implants reached the 100%
      value in 60-80 days with nearly complete enzymatic activity of the last fraction
      of released lysozyme. Pure PLGA implants with up to 20% lysozyme loading could be
      formulated without initial burst. The incorporation of PEG 400 reduced the
      initial burst at drug loadings in excess of 20%. CONCLUSION: A complete lysozyme
      recovery in active form with a burst-free and complete release from PLGA implants
      prepared by hot-melt extrusion was obtained. This is in contrast to many reported
      microparticulate lysozyme-PLGA systems and suggests the great potential of hot
      melt extrusion for the preparation of protein-PLGA implants.

PMID- 20033475
TI  - Pegylated phospholipids-based self-assembly with water-soluble drugs.
AB  - PURPOSE: To investigate the self-assembly of polyethylene glycol (PEG)
      phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin
      hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight
      into the mechanism of formation and mode of interaction of the drug with PEG-PE
      as well as the general principles of self-assembly using pegylated lipid
      micelles. METHODS: One-step self-assembly method to prepare drug-loaded micelles
      was developed. The micelles were characterized by dynamic light scattering,
      transmission electron microscopy, encapsulation efficiency, and release study.
      NMR was used to study molecular assembly of PEG-PE with doxorubicin. RESULTS:
      Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles
      with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs,
      respectively. Drug loading did not measurably perturb either the geometry or the
      size. It was found that electrostatic interaction and hydrophobic forces are
      responsible for the intercalation of drugs into PEG-PE micelles. NMR data
      revealed that the anthracycline ring of doxorubicin was inserted between PE
      phospholipids, and its amino sugar located in the outer shell of micelle between
      PEG chains. CONCLUSION: Based on our results, the structure and self-assembly
      mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed.

PMID- 20033477
TI  - Evaluation of different tests based on observations for external model evaluation
      of population analyses.
AB  - To evaluate by simulation the statistical properties of normalized prediction
      distribution errors (NPDE), prediction discrepancies (pd), standardized
      prediction errors (SPE), numerical predictive check (NPC) and decorrelated NPC
      (NPC(dec)) for the external evaluation of a population pharmacokinetic analysis,
      and to illustrate the use of NPDE for the evaluation of covariate models. We
      assume that a model M(B) has been built using a building dataset B, and that a
      separate validation dataset, V is available. Our null hypothesis H(0) is that the
      data in V can be described by M(B). We use several methods to test this
      hypothesis: NPDE, pd, SPE, NPC and NPC(dec). First, we evaluated by simulation
      the type I error under H(0) of different tests applied to the four methods. We
      also propose and evaluate a single global test combining normality, mean and
      variance tests applied to NPDE, pd and SPE. We perform tests on NPC and NPC(dec),
      after a decorrelation. M(B) was a one compartment model with first order
      absorption (without covariate), previously developed from two phase II and one
      phase III studies of the antidiabetic drug, gliclazide. We simulated 500 external
      datasets according to the design of a phase III study. Second, we investigated
      the application of NPDE to covariate models. We propose two approaches: the first
      approach uses correlation tests or mean comparisons to test the relationship
      between NPDE and covariates; the second evaluates NPDE split by category for
      discrete covariates or quantiles for continuous covariates. We generated several
      validation datasets under H(0) and under alternative assumptions with a model
      without covariate, with one continuous covariate (weight), or one categorical
      covariate (sex). We calculated the powers of the different tests using
      simulations, where the covariates of the phase III study were used. The
      simulations under H(0) show a high type I error for the different tests applied
      to SPE and an increased type I error for pd. The different tests present a type I
      error close to 5% for the global test appied to NPDE. We find a type I error
      higher than 5% for the test applied to classical NPC but this test becomes close
      to 5% for NPC(dec). For covariate models, when model and validation dataset are
      consistent, type I error of the tests are close to 5% for both effects. When
      validation datasets and models are not consistent, the tests detect the
      correlation between NPDE and the covariate. We recommend to use NPDE over SPE for
      external model evaluation, since they do not depend on an approximation of the
      model and have good statistical properties. NPDE represent a better approach than
      NPC, since in order to perform tests on NPC, a decorrelation step must be applied
      before. NPDE, in this illustration, is also a good tool to evaluate model with or
      without covariates.

PMID- 20033476
TI  - Therapeutic potential of new 4-hydroxy-tamoxifen-loaded pH-gradient liposomes in
      a multiple myeloma experimental model.
AB  - PURPOSE: To determine the better liposomal formulation incorporating the active
      metabolite of tamoxifen, 4-hydroxy-tamoxifen (4HT) and the biological impact of
      4HT-pH-gradient liposomes on response to in vivo treatment. METHODS: Several
      pegylated liposomes were formulated by varying the composition of lipids,
      increasing external pH from 7.4 to 9.0 and doubling the lipid concentration.
      Dipalmitoylphosphatidylcholine / cholesterol / distearoylphosphoethanolamine
      poly(ethylene)glycol liposomes (DL-9 liposomes) were chosen for their physico
      chemical properties. Toxicity and release kinetics were assessed in breast cancer
      MCF-7 as well as in multiple myeloma (MM) cells. In vivo antitumor activity and
      bio-distribution were measured in the RPMI8226 MM model. RESULTS: Compared to
      conventional non-pH-gradient liposomes, 4HT-DL-9 liposomes resulted in
      concentration of up to 1 mM 4HT, greater stability, relative toxicity and slow
      4HT release. Intravenous injections of 4HT-DL-9 liposomes at 4 mg/kg/week blocked
      MM tumor growth. Ki67 and CD34 labeling decreased in treated tumors,
      concomitantly with increase of activated caspase-3 supporting a cell
      proliferation arrest, a decrease of tumor vasculature and the induction of tumor
      cell death. CONCLUSION: This antitumor effect was assumed to be the result of a
      modified biodistribution of 4HT once trapped in DL-9 liposomes. Such 4HT
      containing pH-gradient Stealth nanocarriers could be helpful for MM treatment.

PMID- 20033478
TI  - RANKL and OPG mRNA level after non-surgical periodontal treatment.
AB  - Recent research evidence shows that the receptor activator of nuclear factor
      kappa B ligand (RANKL) and osteoprotegerin (OPG) play an important role in
      osteoclastogenesis and the inflammatory bone loss during periodontitis. Bone
      remodeling process is dependent on the balance of these two proteins while a high
      ratio of RANKL/OPG characterizes the increased osteolytic process and it has been
      reported in inflammatory diseases including the periodontal disease. The purpose
      of this study was to determine the OPG and RANKL mRNA levels in periodontal
      tissues derived from patients with advanced chronic periodontitis after non
      surgical periodontal therapy (SRP) and to compare the RANKL/OPG ration with that
      in healthy persons. Gingival biopsies were obtained from subjects with clinically
      healthy periodontium (H) (N = 11) and patients with advanced chronic
      periodontitis (CP) (N = 14). Total RNA was isolated from the gingival samples and
      1 microg RNA was reverse transcribed to cDNA, followed by polymerase chain
      reaction (PCR) using specific primers for OPG and RANKL. The efficiency of
      reverse transcription was verified by the amplification of the GAPDH gene. The
      intensity of RT-PCR products was analyzed by a densitometer and was normalized to
      the intensity of the band for the housekeeping gene GAPDH. Immunohistochemical
      evaluation of the RANKL and OPG expression was also performed. The expression of
      RANKL as well as of OPG was reduced in CP specimens in comparison to that of
      healthy persons in a statistical significant way. However, the RANKL/OPG ratio
      showed to be slightly elevated in CP compared to H specimens but this finding was
      not of statistical significance. The immunohistochemical analysis revealed a non
      uniform expression pattern for both proteins. Although further investigation is
      needed to identify the specific role of RANKL and OPG protein in periodontitis
      progression, our data after SRP might indicate the possible involvement of these
      proteins in the activation of pathways, which regulate the repair of the
      periodontal tissues.

PMID- 20033479
TI  - Multiple therapeutic effects of adjunctive baicalin therapy in experimental
      bacterial meningitis.
AB  - This study aimed to examine effects of adjunctive baicalin therapy to ampicillin
      for experimental bacterial meningitis in rabbits. After Escherichia Coli
      inoculation, mean leukocyte counts, concentrations of protein, tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 (IL-1) and lactate in cerebrospinal fluid
      (CSF), brain water content and mean arterial and intracranial pressures
      substantially increased in the meningitis group. Ampicillin alone for 5 h
      markedly exacerbated the enhanced leukocyte counts and protein concentration, and
      showed no significant effect on the elevated CSF TNF-alpha, IL-1 and lactate
      concentration, mean arterial and intracranial pressures, and brain water content.
      Baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone, C(21)H(18)O(11)) completely
      counteracted ampicillin-induced exacerbation, and further alleviated the enhanced
      mean leukocyte counts and protein concentration when combined with ampicillin.
      Adjunctive baicalin also significantly ameliorated the elevated CSF TNF-alpha, IL
      1 and lactate concentration, mean arterial and intracranial pressures, and brain
      water content. Baicillin, as an adjunctive treatment exerted multiple therapeutic
      effects in experimental bacterial meningitis.

PMID- 20033481
TI  - No association between CYP1B1 Val432Leu polymorphism and breast cancer risk: a
      meta-analysis involving 40,303 subjects.
AB  - Breast cancer is the most common cancer in women. To date, many publications have
      evaluated the association between Cytochrome P450 1B1 (CYP1B1) Val432Leu
      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. By searching Medline, Pubmed, and ISI Web of Knowledge
      databases, 26 studies including 19,028 cases and 21,275 controls were collected
      for CYP1B1 Val432Leu polymorphism. Crude ORs with 95% CIs were used to assess the
      strength of association between CYP1B1 Val432Leu polymorphism and breast cancer
      risk. The pooled ORs were performed for codominant model, dominant model, and
      recessive model, respectively. Overall, no significant associations between
      CYP1B1 Val432Leu polymorphism and breast cancer susceptibility were found for
      Val/Val versus Leu/Leu (OR = 0.98; 95% CI: 0.90-1.06), Val/Leu versus Leu/Leu (OR
      = 1.01; 95% CI: 0.93-1.09), Val/Val + Val/Leu versus Leu/Leu (OR = 1.00; 95% CI:
      0.93-1.08) and Val/Val versus Val/Leu + Leu/Leu (OR = 0.96; 95% CI: 0.91-1.01).
      In the stratified analysis by ethnicity, menopausal status and sources of
      controls, significant associations were still not observed in all genetic models.
      In conclusion, this meta-analysis provides strong evidence that CYP1B1 Val432Leu
      polymorphism is not associated with breast cancer risk.

PMID- 20033483
TI  - Broad BRCA1 and BRCA2 mutational spectrum and high incidence of recurrent and
      novel mutations in the eastern Spain population.

PMID- 20033482
TI  - Dietary lignan intakes in relation to survival among women with breast cancer:
      the Western New York Exposures and Breast Cancer (WEB) Study.
AB  - Dietary lignan intakes have been associated with reduced breast cancer risks;
      however, no previous studies have investigated whether lignan intake might be
      associated with breast cancer survival. We examined the association of dietary
      lignan intakes with survival in 1122 women with primary, incident, histologically
      confirmed breast cancer identified between 1996 and 2001, and with vital status
      determined through December 31, 2006. Diet in the 12-24 months before diagnosis
      was assessed with an extensive food frequency questionnaire, and potential
      confounders assessed from an extensive epidemiologic interview and abstracted
      clinical data. Lignan intake was calculated using published food composition
      data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan
      intakes with all cause, and breast cancer mortality were estimated using Cox
      proportional hazards adjusting for age, education, race, total energy intake,
      tumor stage, and body mass index. Of the 1122 women with complete dietary data,
      160 had died by the end of follow-up. Among postmenopausal women only, those in
      the highest versus lowest quartile of lignan intakes had a statistically
      significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26
      0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95%
      CI 0.11-0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36-1.03), but not
      fruits, vegetables, or grains, were also weakly associated with overall
      mortality. In summary, our results suggest that higher lignan intakes may be
      associated with improved survival among postmenopausal women with breast cancer.

PMID- 20033484
TI  - Gene amplification in ductal carcinoma in situ of the breast.
AB  - Multiple different biologically and clinically relevant genes are often amplified
      in invasive breast cancer, including HER2, ESR1, CCND1, and MYC. So far, little
      is known about their role in tumor progression. To investigate their significance
      for tumor invasion, we compared pure ductal carcinoma in situ (DCIS) and DCIS
      associated with invasive cancer with regard to the amplification of these genes.
      Fluorescence in situ hybridization (FISH) was performed on a tissue microarray
      containing samples from 130 pure DCIS and 159 DCIS associated with invasive
      breast cancer. Of the latter patients, we analyzed the intraductal and invasive
      components separately. In addition, lymph node metastases of 23 patients with
      invasive carcinoma were included. Amplification rates of pure DCIS and DCIS
      associated with invasive cancer did not differ significantly (pure DCIS vs. DCIS
      associated with invasive cancer: HER2 22.7 vs. 24.2%, ESR1 19.0 vs. 24.1%, CCND1
      10.0 vs. 14.8%, MYC 11.8 vs. 6.5%; P > 0.05). Furthermore, we observed a high
      concordance of the amplification status for all genes if in situ and invasive
      carcinoma of individual patients were compared. This applied also to the
      corresponding lymph node metastases. Our results indicate no significant
      differences between the gene amplification status of DCIS and invasive breast
      cancer concerning HER2, ESR1, CCND1, and MYC. Therefore, our data suggest an
      early role of all analyzed gene amplifications in breast cancer development but
      not in the initiation of invasive tumor growth.

PMID- 20033485
TI  - Bioaccumulation and biotransformation of decabromodiphenyl ether and effects on
      daily growth in juvenile lake whitefish (Coregonus clupeaformis).
AB  - Decabromodiphenyl ether (BDE 209) is the main congener in the commonly used
      commercial flame retardant mixture, "deca-BDE". There is evidence showing that
      fish can debrominate BDE 209 into potentially more toxic congeners. The objective
      of this study was to evaluate BDE 209 uptake and its potential effects on
      juvenile lake whitefish (Coregonus clupeaformis). Lake whitefish were fed BDE 209
      at four nominal concentrations (control, 0.1, 1, and 2 microg/g-diet) for 30
      days. Livers and carcasses were analyzed for 11 polybrominated diphenyl ether
      (PBDE) congeners (BDE 47, 99, 100, 153, 154, 196, 197, 206, 207, 208, and 209)
      and daily otolith increment width was measured as an estimate of growth before
      and after exposure. Four congeners (BDE 206, 207, 208, and 209) were detected in
      livers and carcasses. Hepatic BDE 209 concentrations in the 1 and 2 microg/g
      treatments were significantly higher than in the control group (1.25 and 5.80
      nmol/g-lipid compared to 0.183 nmol/g-lipid). The concentration of BDE 209
      detected in the tissues of the control group resulted from BDE 209 in the base
      diets. Concentrations of all congeners from the 1 and 2 microg/g groups were
      higher in livers than carcasses, indicating the liver was the primary organ of
      BDE 209 accumulation. Compared to the fraction in diets, the molar fraction of
      BDE 209 was lower in livers and carcasses, whereas the fractions of BDE 206, 207,
      and 208 were higher. These different distributions of PBDE congeners resulted
      from differential adsorption and metabolism. One congener, BDE 206, could be a
      major metabolite from BDE 209 debromination. Otolith increment widths were
      narrower in fish from the highest diet concentration administered, suggesting BDE
      209 may have affected growth rates. In conclusion, this in vivo study with lake
      whitefish showed that BDE 209 was debrominated into lower PBDE congeners and that
      exposure to 2 microg/g may have affected fish growth.

PMID- 20033486
TI  - Integrated assessment of water quality of the Costa da Morte (Galicia, NW Spain)
      by means of mussel chemical, biochemical and physiological parameters.
AB  - The aim of this study was to assess environmental quality at some of the sites
      most severely affected by the Prestige oil spill off 2 years after the spillage
      (April and November 2004). For this purpose analyses of polycyclic aromatic
      hydrocarbons (PAH) and several biochemical (antioxidant enzymes catalase,
      glutathione reductase, glutathione peroxidase, superoxide dismutase and DT
      diaphorase and lipid peroxidation) and physiological [scope for growth (SFG)]
      biomarkers were determined on wild mussel populations (Mytilus galloprovincialis)
      collected at four points along the Costa da Morte and compared with those of a
      reference site not affected by the oil spill. Results showed that PAH contents
      had markedly decreased 17 months after the accident, although they were higher in
      April than in November, when they showed values similar to background levels
      reported for this area. Nevertheless, the predominance of chrysene on PAH
      profiles, similarly to findings obtained immediately after the spill, indicated
      the Prestige as their main source. In spite of the low PAH levels recorded,
      antioxidant activity levels (explained through the integrated antioxidant
      response-IAR) were higher in the Costa da Morte than at the reference site either
      in April and November. In April IAR seems to be related to PAH levels found 3
      months after the accident (February 2003), suggesting the persistence in the
      environment of oxidative stress-producing components from the spill. However,
      evidence of oxidative stress was not reflected at physiological level by scope
      for growth, with only very slight differences being observed between values from
      the reference site and those from Costa da Morte sites. In conclusion, although 2
      years after the spill PAHs bioaccumulated by mussels from the Costa da Morte had
      decreased to background levels, biochemical parameters showed signals of
      oxidative stress in mussels from this area. However, SFG reflected a good health
      status for the mussel populations studied and did not reveal evidence of
      physiological disturbance either 17 or 24 months after the Prestige spill.

PMID- 20033487
TI  - Masitinib for the treatment of canine atopic dermatitis: a pilot study.
AB  - There is an on-going need to identify medications suitable for the long-term
      treatment of canine atopic dermatitis (CAD). Masitinib mesilate is a potent and
      selective tyrosine kinase inhibitor of the c-KIT receptor. A strong relationship
      exists between the SCF/c-KIT pathway and pathogenesis of CAD, suggesting that
      masitinib may potentially fulfil the above role. This study reports on an
      uncontrolled pilot study of masitinib in CAD. Masitinib was administered orally
      to 11 dogs at a mean dose of 11.0 +/- 1.83 mg/kg/day (free base) for 28 days.
      Treatment response was assessed by evolution of clinical appearance according to
      a modified version of the Canine Atopic Dermatitis Extent and Severity Index
      (mCADESI), pruritus scale and surface area of lesions. Masitinib improved CAD
      with a mean reduction in mCADESI of 50.7 +/- 29.8% (95% C.I. = 29.4-72.0; p =
      0.0004) at day 28 relative to baseline, with 8/10, 8/10 and 4/10 dogs showing
      improvement of >or=33%, >or=40% and >or=50%, respectively. Improvement was
      further evidenced by a decrease in pruritus score and the surface area of
      lesions. No serious or severe adverse events occurred during this trial, although
      6/11 dogs presented with mild to moderate treatment related adverse events. There
      is sufficient compelling evidence to warrant further investigation.

PMID- 20033488
TI  - Integrating wellness, recovery, and self-management for mental health consumers.
AB  - Three distinct, yet interrelated, terms-wellness, recovery, and self-management
      have received increasing attention in the research, consumer, and provider
      communities. This article traces the origins of these terms, seeking to
      understand how they apply, individually and in conjunction with one another to
      mental health consumers. Each shares a common perspective that is health-centered
      rather than disease-centered and that emphasizes the role of consumers as opposed
      to professional providers as the central determinants of health and well-being.
      Developing approaches combining elements of each construct may hold promise for
      improving the overall health and well-being of persons with serious mental
      disorders.

PMID- 20033489
TI  - Echocardiography as a guidance in CRT management: the GPS system in a labyrinth?
AB  - Although progress has been made to understand the factors for non-responsiveness,
      fine tuning and comprehensive strategies are needed to make echocardiography the
      GPS system in cardiac resynchronization. Taking the wrong turn in the labyrinth
      of dyssynchrony is expensive and time consuming without improving well being of
      the heart failure patient. Possibly other imaging techniques could help in fine
      tuning cardiac resynchronization.

PMID- 20033490
TI  - Assessment of image quality and radiation dose in prospective ECG-triggered
      coronary CT angiography compared with retrospective ECG-gated coronary CT
      angiography.
AB  - We sought to determine the cut-off point of the average heart rate (HR) and HR
      differences in obtaining diagnostic image quality using prospective
      electrocardiographically-triggered (PT) coronary computed tomographic angiography
      (CCTA) and to compare image quality and radiation dose for CCTA obtained with PT
      CCTA and retrospective electrocardiographically-gated (RG) CCTA. A total of 178
      patients who were referred for CCTA were enrolled in the study. Two independent
      radiologists evaluated subjective image quality. The non-diagnostic coronary
      segments were 32 of 1,226 segments (2.6%) for PT CCTA and 12 of 1,346 segments
      (0.9%) for RG CCTA (P < 0.001). The mean image quality scores for PT CCTA and RG
      CCTA were 3.82 +/- 0.29 and 3.93 +/- 0.14, respectively. The mean radiation dose
      of patients that underwent PT CCTA was 3.83 +/- 0.84 mSv and RG CCTA 10.7 +/-
      2.70 mSv. For patients who underwent PT CCTA, image quality was inversely related
      to HR (56.5 +/- 4.3 bpm; r = 0.38; P < 0.001) and HR differences (2.8 +/- 2.7
      bpm; r = 0.49; P < 0.001). With the use of receiver operator characteristic
      analysis, a cut-off HR of 57 bpm (58% sensitivity, 67% specificity) and HR
      difference of 6 bpm (93% sensitivity, 46% specificity) were the best threshold
      for the prediction of diagnostic image quality. In patients with a regular, low
      HR, PT CCTA offers diagnostic image quality and substantially reduces effective
      radiation compared with the use of RG CCTA with dose modulation.

PMID- 20033491
TI  - Prenatal double aortic arch presenting with a right aortic arch and an anomalous
      artery arising from the ascending aorta.
AB  - Double aortic arch is a rare anomaly of the aortic arch and this may cause
      tracheal damage by compressing the trachea during the first year of life. We
      report here on three fetal cases of double aortic arch and their outcomes. These
      malformations presented as an isolated right aortic arch or as a typical vascular
      ring form on the prenatal echocardiography that was obtained between 22 and 24
      weeks gestation. In two of the three patients, the major intracardiac anomaly was
      a ventricular septal defect, and this was associated with the aortic
      malformation. A more detailed evaluation of the branching pattern of the aorta,
      and particularly whether the aorta gives off a left-sided limb of the double
      arch, could suggest the diagnosis of a double aortic arch in utero. Two patients
      underwent successful surgical correction and they showed good clinical outcomes.
      Fetal double aortic arch can be prenatally suspected after performing fetal
      echocardiography for those fetuses that show a right side aortic arch, and this
      can help to avoid delaying the postnatal management of this rare anomaly.

PMID- 20033492
TI  - Using DNA barcodes to identify a bird involved in a birdstrike at a Chinese
      airport.
AB  - One day at dusk in August, 200X, an airplane was struck by a bird at a Chinese
      airport (M Airport). After a careful check, some blades of the plane's engine
      were found to be out of shape and a few feathers and some bloodstains were found
      in the air intake of the engine. In order to know which species of bird was
      involved in the birdstrike, firstly we extracted DNA from the bloodstains;
      secondly, the DNA barcode (portion of COI gene) of the unknown species was
      amplified by PCR method; thirdly, sequence divergences (K2P differences) of the
      DNA barcode between the unknown species and a library of 59 common bird species
      distributed at the airport area were analyzed. Furthermore, a neighbor-joining
      (NJ) tree based on COI barcodes was created to provide graphic representation of
      sequence divergences among the species to confirm the identification. The result
      showed that red-rumped swallow (Hirundo daurica) was involved in the birdstrike
      incident. Some suggestions to avoid birdstrikes caused by red-rumped swallows
      were given to the administrative department of M Airport to ensure flying safety.

PMID- 20033493
TI  - 7th Annual meeting of the German Society of Computer and Robot-assisted Surgery
      (CURAC.08).

PMID- 20033494
TI  - A comparison of ground truth estimation methods.
AB  - PURPOSE: Knowledge of the exact shape of a lesion, or ground truth (GT), is
      necessary for the development of diagnostic tools by means of algorithm
      validation, measurement metric analysis, accurate size estimation. Four methods
      that estimate GTs from multiple readers' documentations by considering the
      spatial location of voxels were compared: thresholded Probability-Map at 0.50
      (TPM(0.50)) and at 0.75 (TPM(0.75)), simultaneous truth and performance level
      estimation (STAPLE) and truth estimate from self distances (TESD). METHODS: A
      subset of the publicly available Lung Image Database Consortium archive was used,
      selecting pulmonary nodules documented by all four radiologists. The pair-wise
      similarities between the estimated GTs were analyzed by computing the respective
      Jaccard coefficients. Then, with respect to the readers' marking volumes, the
      estimated volumes were ranked and the sign test of the differences between them
      was performed. RESULTS: (a) the rank variations among the four methods and the
      volume differences between STAPLE and TESD are not statistically significant, (b)
      TPM(0.50) estimates are statistically larger (c) TPM(0.75) estimates are
      statistically smaller (d) there is some spatial disagreement in the estimates as
      the one-sided 90% confidence intervals between TPM(0.75) and TPM(0.50), TPM(0.75)
      and STAPLE, TPM(0.75) and TESD, TPM(0.50) and STAPLE, TPM(0.50) and TESD, STAPLE
      and TESD, respectively, show: [0.67, 1.00], [0.67, 1.00], [0.77, 1.00], [0.93,
      1.00], [0.85, 1.00], [0.85, 1.00]. CONCLUSIONS: The method used to estimate the
      GT is important: the differences highlighted that STAPLE and TESD,
      notwithstanding a few weaknesses, appear to be equally viable as a GT estimator,
      while the increased availability of computing power is decreasing the appeal
      afforded to TPMs. Ultimately, the choice of which GT estimation method, between
      the two, should be preferred depends on the specific characteristics of the
      marked data that is used with respect to the two elements that differentiate the
      method approaches: relative reliabilities of the readers and the reliability of
      the region boundaries.

PMID- 20033495
TI  - Combined surface and volume processing for fused joint segmentation.
AB  - PURPOSE: Segmentation of rheumatoid joints from CT images is a complicated task.
      The pathological state of the joint results in a non-uniform density of the bone
      tissue, with holes and irregularities complicating the segmentation process. For
      the specific case of the shoulder joint, existing segmentation techniques often
      fail and lead to poor results. This paper describes a novel method for the
      segmentation of these joints. METHODS: Given a rough surface model of the
      shoulder, a loop that encircles the joint is extracted by calculating the minimum
      curvature of the surface model. The intersection points of this loop with the
      separate CT-slices are connected by means of a path search algorithm. Inaccurate
      sections are corrected by iteratively applying a Hough transform to the
      segmentation result. RESULTS: As a qualitative measure we calculated the Dice
      coefficient and Hausdorff distances of the automatic segmentations and expert
      manual segmentations of CT-scans of ten severely deteriorated shoulder joints.
      For the humerus and scapula the median Dice coefficient was 98.9% with an
      interquartile range (IQR) of 95.8-99.4 and 98.5% (IQR 98.3-99.2%), respectively.
      The median Hausdorff distances were 3.06 mm (IQR 2.30-4.14) and 3.92 mm (IQR 1.96
      -5.92 mm), respectively. CONCLUSION: The routine satisfies the criterion of our
      particular application to accurately segment the shoulder joint in under 2 min.
      We conclude that combining surface curvature, limited user interaction and
      iterative refinement via a Hough transform forms a satisfactory approach for the
      segmentation of severely damaged arthritic shoulder joints.

PMID- 20033496
TI  - Optimization of acquisition trajectories for 3D rotational coronary venography.
AB  - OBJECTIVE: Rotational coronary X-ray imaging on C-arm systems provides a
      multitude of diagnostic projections from the vascular tree with a single contrast
      agent bolus. The acquisition trajectory is typically limited to a circular arc
      with a fixed caudo-cranial angulation. This may cause sub- optimal projection
      directions for specific vessel segments for all acquired views, e.g., those
      segments orthogonal to the axis of rotation. In this paper, a method is presented
      to calculate a patient-independent acquisition trajectory with respect to vessel
      foreshortening and overlap for multiple vessel segments of the coronary tree.
      This method can be applied to artery as well as vein anatomy. METHODS: Rotational
      coronary venograms of 14 patients have been used to generate three-dimensional
      mesh representations with a semi-automatic two view modeling algorithm. The
      venous tree is divided into seven different vessel segments. Foreshortening and
      overlap of every segment are calculated and combined for all patients in a
      measure called obstruction value. The weighted obstruction values of all vessel
      segments define a cost function for the entire two-dimensional angular range of
      the C-arm system. Viterbi's algorithm is used to calculate an optimal trajectory
      with respect to this cost function. The method is validated by leave-one-out
      cross-validation on the 14 rotational venography data sets and on simulated
      venograms of a segmented computed tomography (CT) data set. Projection images
      with a foreshortening value below 10% and overlap below 20% are rated 'optimal'.
      RESULTS: In 12 (85.7%) data sets, 43% more optimal images were acquired using the
      presented method compared to the standard circular arc trajectory. As well, in 13
      (92.8%) data sets 38% more vessel segments can be optimally visualized in the
      acquired images. The test on the CT data set showed that the resulting average
      root-mean-square error of the extracted centerline points of the segmented CT
      data set compared to the error based on the views from the circular arc was
      reduced from 2.52 to 1.55 mm. CONCLUSION: In a first test, the method proved to
      deliver improved image quality by reducing foreshortening and overlap of vessel
      segments and may therefore also improve the centerline extraction accuracy of the
      semi-automatic two view modeling method.

PMID- 20033497
TI  - Intra-operative virtual endoscopy for image guided endonasal transsphenoidal
      pituitary surgery.
AB  - PURPOSE: Virtual endoscopy has already proven its benefit for pre-operative
      planning of endoscopic pituitary surgery. The translation of such a system into
      the operating room is a logical consequence, but only a few general intra
      operative image guided systems providing virtual endoscopic images have been
      proposed so far. A discussion of related visualization and interaction problems
      occurring during sinus and pituitary surgery is still missing. METHODS: This
      paper aims at filling this gap and proposes a system that integrates an existing
      virtual endoscopy system originally designed for pre-operative planning of
      pituitary surgery with a professional intra-operative navigation system.
      Visualization and interaction possibilities of the pre-operative planning system
      have been extended to fulfill the special requirements to the system if used for
      intra-operative navigation of endonasal transsphenoidal pituitary surgery.
      RESULTS: The feasibility of the system has been successfully tested on 1 cadaver
      and 12 patients. The virtual endoscopic images were found useful (1) during the
      endonasal transsphenoidal approach in cases of anatomic variations and for the
      individually tailored opening of the sellar floor, and (2) during tumor resection
      for respecting the internal carotid artery. The visualization of hidden
      anatomical structures behind the bony walls of the sphenoid sinus during the
      sellar phase of the surgery has been found most beneficial. DISCUSSION: According
      to our data, intra-operative virtual endoscopy provides additional anatomical
      information to the surgeon. By depicting individual anatomical variations in
      advance, it may add to the safety of this frequent neurosurgical procedure.

PMID- 20033498
TI  - Computer-aided diagnosis of lumbar disc pathology from clinical lower spine MRI.
AB  - PURPOSE: Detection of abnormal discs from clinical T2-weighted MR Images. This
      aids the radiologist as well as subsequent CAD methods in focusing only on
      abnormal discs for further diagnosis. Furthermore, it gives a degree of
      confidence about the abnormality of the intervertebral discs that helps the
      radiologist in making his decision. MATERIALS AND METHODS: We propose a
      probabilistic classifier for the detection of abnormality of intervertebral
      discs. We use three features to label abnormal discs that include appearance,
      location, and context. We model the abnormal disc appearance with a Gaussian
      model, the location with a 2D Gaussian model, and the context with a Gaussian
      model for the distance between abnormal discs. We infer on the middle slice of
      the T2-weighted MRI volume for each case. These MRI scans are specific for the
      lumbar area. We obtain our gold standard for the ground truth from our
      collaborating radiologist group by having the clinical diagnosis report for each
      case. RESULTS: We achieve over 91% abnormality detection accuracy in a cross
      validation experiment with 80 clinical cases. The experiment runs ten rounds; in
      each round, we randomly leave 30 cases out for testing and we use the other 50
      cases for training. CONCLUSION: We achieve high accuracy for detection of
      abnormal discs using our proposed model that incorporates disc appearance,
      location, and context. We show the extendability of our proposed model to
      subsequent diagnosis tasks specific to each intervertebral disc abnormality such
      as desiccation and herniation.

PMID- 20033499
TI  - Tracking of the liver for navigation in open surgery.
AB  - PURPOSE: A main task of navigation systems assisting a surgeon during an
      intervention is to determine the spatial position of instruments relative to the
      organ. In comparison to navigation of hard tissue, this is still a challenge for
      navigation in soft tissue. In this contribution a method is presented to measure
      the position and the deformation of the liver. METHOD: Therefore, reflective
      fiducials are fixed at the surface of the liver, whose spatial positions are
      measured with an optical position measurement system. Therewith the position of
      the whole liver is calculated. The deformation at the surface of the liver is
      determined using a model of the surface. The method was verified in an experiment
      with pig liver. RESULTS: The position of the liver could be tracked. Spatial
      deviations because of the deformation of the liver could be reduced by 36%.
      CONCLUSION: This method can be applied in navigation of instruments in open liver
      surgery to track the position of the liver.

PMID- 20033500
TI  - A fully 3D work context for oral implant planning and simulation.
AB  - PURPOSE: Most software systems for oral implantology are based on a two
      dimensional multi-view approach, often accompanied with a surface rendered model.
      Usually they are affected by common errors like anisotropy of the volume and
      distortion on measurements. A more integrated and realistic 3D approach for
      implant surgery is desirable in order to gain a deeper and surer knowledge of
      patient's anatomy before inserting the implants, thus reducing the risk of
      damaging surrounding structures. METHODS: We present a 3D software system for
      oral implant planning where computer graphic techniques have been used to create
      a smooth and user-friendly fully integrated 3D environment to work in. Both
      volume isotropy and correctness in measurements are obtained through slices
      interpolation to achieve, respectively, an isotropic voxel and the freedom of
      choosing arbitrarily, during the planning, the best cross-sectional plane.
      Correct orientation of the planned implants is also easily computed, by
      exploiting a radiological mask with radio-opaque markers, worn by the patient
      during the CT scan. RESULTS: Precision in measures was validated by considering
      several different scans and comparing the measures achieved with the ones got
      through the common methodology. It has been also calculated error percentages,
      algorithms efficiencies, and performances. Precision achieved outperforms usual
      DentaScan multi-view approach one, and it is comparable with or better than that
      obtained by the DentalVox tool (from 0.16 to 0.71% error in measures).
      CONCLUSIONS: The proposed software system provides a user-friendly, correct and
      precise work context for oral implant planning, avoiding similar software common
      errors. The 3D environment can be also exploited in the final surgical phase, in
      order to provide a flapless surgical guide, through the use of an anthropomorphic
      robot.

PMID- 20033501
TI  - Integrating automatic and interactive methods for coronary artery segmentation:
      let the PACS workstation think ahead.
AB  - PURPOSE: To present newly developed software that can provide fast coronary
      artery segmentation and accurate centerline extraction for later lesion
      visualization and quantitative measurement while minimizing user interaction.
      METHODS: Previously reported fully automatic and interactive methods for coronary
      artery extraction were optimized and integrated into a user-friendly workflow.
      The user's waiting time is saved by running the non-supervised coronary artery
      segmentation and centerline tracking in the background as soon as the images are
      received. When the user opens the data, the software provides an intuitive
      interactive analysis environment. RESULTS: The average overlap between the
      centerline created in our software and the reference standard was 96.0%. The
      average distance between them was 0.38 mm. The automatic procedure runs for 1.4
      2.5 min as a single-thread application in the background. Interactive processing
      takes 3 min in average. CONCLUSION: In preliminary experiments, the software
      achieved higher efficiency than the former interactive method, and reasonable
      accuracy compared to manual vessel extraction.

PMID- 20033502
TI  - Seeded ND medical image segmentation by cellular automaton on GPU.
AB  - PURPOSE: We present a GPU-based framework to perform organ segmentation in N
      dimensional (ND) medical image datasets by computation of weighted distances
      using the Ford-Bellman algorithm (FBA). Our GPU implementation of FBA gives an
      alternative and optimized solution to other graph-based segmentation techniques.
      METHODS: Given a number of K labelled-seeds, the segmentation algorithm evolves
      and segments the ND image in K objects. Each region is guaranteed to be connected
      to seeds with the same label. The method uses a Cellular Automata (CA) to compute
      multiple shortest-path-trees based on the FBA. The segmentation result is
      obtained by K-cuts of the graph in order to separate it in K sets. A quantitative
      evaluation of the method was performed by measuring renal volumes of 20 patients
      based on magnetic resonance angiography (MRA) acquisitions. Inter-observer
      reproducibility, accuracy and validity were calculated and associated computing
      times were recorded. In a second step, the computational performances were
      evaluated with different graphics hardware and compared to a CPU implementation
      of the method using Dijkstra's algorithm. RESULTS: The ICC for inter-observer
      reproducibility of renal volume measurements was 0.998 (0.997-0.999) for two
      radiologists and the absolute mean difference between the two readers was lower
      than 1.2% of averaged renal volumes. The validity analysis shows an excellent
      agreement of our method with the results provided by a supervised segmentation
      method, used as reference. CONCLUSIONS: The formulation of the FBA in the form of
      a CA is simple, efficient and straightforward, and can be implemented in low cost
      vendor-independent graphics hardware. The method can efficiently be applied to
      perform organ segmentation and quantitative evaluation in clinical routine.

PMID- 20033503
TI  - Effect of brain shift on the creation of functional atlases for deep brain
      stimulation surgery.
AB  - PURPOSE: In the recent past many groups have tried to build functional atlases of
      the deep brain using intra-operatively acquired information such as stimulation
      responses or micro-electrode recordings. An underlying assumption in building
      such atlases is that anatomical structures do not move between pre-operative
      imaging and intra-operative recording. In this study, we present evidences that
      this assumption is not valid. We quantify the effect of brain shift between pre
      operative imaging and intra-operative recording on the creation of functional
      atlases using intra-operative somatotopy recordings and stimulation response
      data. METHODS: A total of 73 somatotopy points from 24 bilateral subthalamic
      nucleus (STN) implantations and 52 eye deviation stimulation response points from
      17 bilateral STN implantations were used. These points were spatially normalized
      on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid
      registration algorithm. Each implantation was categorized as having low, medium
      or large brain shift based on the amount of pneumocephalus visible on post
      operative CT. The locations of somatotopy clusters and stimulation maps were
      analyzed for each category. RESULTS: The centroid of the large brain shift
      cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36
      mm) was found posterior, medial and inferior to that of the medium cluster (2.90,
      13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift
      cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to
      the mid-commissural point. Euclidean distances between the centroids were 1.68,
      2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift
      clusters. We found similar trends for the positions of the stimulation maps. The
      Euclidian distance between the highest probability locations on the low and
      medium-large shift maps was 4.06 mm. CONCLUSION: The effect of brain shift in
      deep brain stimulation (DBS) surgery has been demonstrated using intra-operative
      somatotopy recordings as well as stimulation response data. The results not only
      indicate that considerable brain shift happens before micro-electrode recordings
      in DBS but also that brain shift affects the creation of accurate functional
      atlases. Therefore, care must be taken when building and using such atlases of
      intra-operative data and also when using intra-operative data to validate
      anatomical atlases.

PMID- 20033504
TI  - 3D reconstruction of the human rib cage from 2D projection images using a
      statistical shape model.
AB  - PURPOSE: This paper describes an approach for the three-dimensional (3D) shape
      and pose reconstruction of the human rib cage from few segmented two-dimensional
      (2D) projection images. Our work is aimed at supporting temporal subtraction
      techniques of subsequently acquired radiographs by establishing a method for the
      assessment of pose differences in sequences of chest radiographs of the same
      patient. METHODS: The reconstruction method is based on a 3D statistical shape
      model (SSM) of the rib cage, which is adapted to binary 2D projection images of
      an individual rib cage. To drive the adaptation we minimize a distance measure
      that quantifies the dissimilarities between 2D projections of the 3D SSM and the
      projection images of the individual rib cage. We propose different silhouette
      based distance measures and evaluate their suitability for the adaptation of the
      SSM to the projection images. RESULTS: An evaluation was performed on 29 sets of
      biplanar binary images (posterior-anterior and lateral). Depending on the chosen
      distance measure, our experiments on the combined reconstruction of shape and
      pose of the rib cages yield reconstruction errors from 2.2 to 4.7 mm average mean
      3D surface distance. Given a geometry of an individual rib cage, the rotational
      errors for the pose reconstruction range from 0.1 degrees to 0.9 degrees.
      CONCLUSIONS: The results show that our method is suitable for the estimation of
      pose differences of the human rib cage in binary projection images. Thus, it is
      able to provide crucial 3D information for registration during the generation of
      2D subtraction images.

PMID- 20033505
TI  - Classification and numbering of teeth in multi-slice CT images using wavelet
      Fourier descriptor.
AB  - PURPOSE: Teeth arrangement is essential in face ergonomics and healthiness. In
      addition, they play key roles in forensic medicine. Various computer-assisted
      procedures for medical application in quantitative dentistry require automatic
      classification and numbering of teeth in dental images. METHOD: In this paper, we
      propose a multi-stage technique to classify teeth in multi-slice CT (MSCT)
      images. The proposed algorithm consists of the following three stages:
      segmentation, feature extraction and classification. We segment the teeth by
      employing several techniques including Otsu thresholding, morphological
      operations, panoramic re-sampling and variational level set. In the feature
      extraction stage, we follow a multi-resolution approach utilizing wavelet-Fourier
      descriptor (WFD) together with a centroid distance signature. We compute the
      feature vector of each tooth by employing the slice associated with largest tooth
      tissues. The feature vectors are employed for classification in the third stage.
      We perform teeth classification by a conventional supervised classifier. We
      employ a feed- forward neural network classifier to discriminate different teeth
      from each other. RESULTS: The performance of the proposed method was evaluated in
      the presence of 30 different MSCT data sets including 804 teeth. We compare
      classification results of the WFD technique with Fourier descriptor (FD) and
      wavelet descriptor (WD) techniques. We also investigate the invariance properties
      of the WFD technique. Experimental results reveal the effectiveness of the
      proposed method. CONCLUSION: We provided an integrated solution for teeth
      classification in multi-slice CT datasets. In this regard, suggested segmentation
      technique was successful to separate teeth from each other. The employed WFD
      approach was successful to discriminate and numbering of the teeth in the
      presence of missing teeth. The solution is independent of anatomical information
      such as knowing the sequence of teeth and the location of each tooth in the jaw.

PMID- 20033506
TI  - Open core control software for surgical robots.
AB  - OBJECT: In these days, patients and doctors in operation room are surrounded by
      many medical devices as resulting from recent advancement of medical technology.
      However, these cutting-edge medical devices are working independently and not
      collaborating with each other, even though the collaborations between these
      devices such as navigation systems and medical imaging devices are becoming very
      important for accomplishing complex surgical tasks (such as a tumor removal
      procedure while checking the tumor location in neurosurgery). On the other hand,
      several surgical robots have been commercialized, and are becoming common.
      However, these surgical robots are not open for collaborations with external
      medical devices in these days. A cutting-edge "intelligent surgical robot" will
      be possible in collaborating with surgical robots, various kinds of sensors,
      navigation system and so on. On the other hand, most of the academic software
      developments for surgical robots are "home-made" in their research institutions
      and not open to the public. Therefore, open source control software for surgical
      robots can be beneficial in this field. From these perspectives, we developed
      Open Core Control software for surgical robots to overcome these challenges.
      MATERIALS AND METHODS: In general, control softwares have hardware dependencies
      based on actuators, sensors and various kinds of internal devices. Therefore,
      these control softwares cannot be used on different types of robots without
      modifications. However, the structure of the Open Core Control software can be
      reused for various types of robots by abstracting hardware dependent parts. In
      addition, network connectivity is crucial for collaboration between advanced
      medical devices. The OpenIGTLink is adopted in Interface class which plays a role
      to communicate with external medical devices. At the same time, it is essential
      to maintain the stable operation within the asynchronous data transactions
      through network. In the Open Core Control software, several techniques for this
      purpose were introduced. Virtual fixture is well known technique as a "force
      guide" for supporting operators to perform precise manipulation by using a master
      slave robot. The virtual fixture for precise and safety surgery was implemented
      on the system to demonstrate an idea of high-level collaboration between a
      surgical robot and a navigation system. The extension of virtual fixture is not a
      part of the Open Core Control system, however, the function such as virtual
      fixture cannot be realized without a tight collaboration between cutting-edge
      medical devices. By using the virtual fixture, operators can pre-define an
      accessible area on the navigation system, and the area information can be
      transferred to the robot. In this manner, the surgical console generates the
      reflection force when the operator tries to get out from the pre-defined
      accessible area during surgery. RESULTS: The Open Core Control software was
      implemented on a surgical master-slave robot and stable operation was observed in
      a motion test. The tip of the surgical robot was displayed on a navigation system
      by connecting the surgical robot with a 3D position sensor through the
      OpenIGTLink. The accessible area was pre-defined before the operation, and the
      virtual fixture was displayed as a "force guide" on the surgical console. In
      addition, the system showed stable performance in a duration test with network
      disturbance. CONCLUSION: In this paper, a design of the Open Core Control
      software for surgical robots and the implementation of virtual fixture were
      described. The Open Core Control software was implemented on a surgical robot
      system and showed stable performance in high-level collaboration works. The Open
      Core Control software is developed to be a widely used platform of surgical
      robots. Safety issues are essential for control software of these complex medical
      devices. It is important to follow the global specifications such as a FDA
      requirement "General Principles of Software Validation" or IEC62304. For
      following these regulations, it is important to develop a self-test environment.
      Therefore, a test environment is now under development to test various
      interference in operation room such as a noise of electric knife by considering
      safety and test environment regulations such as ISO13849 and IEC60508. The Open
      Core Control software is currently being developed software in open-source manner
      and available on the Internet. A communization of software interface is becoming
      a major trend in this field. Based on this perspective, the Open Core Control
      software can be expected to bring contributions in this field.

PMID- 20033507
TI  - A multimedia electronic patient record (ePR) system for image-assisted minimally
      invasive spinal surgery.
AB  - PURPOSE: This paper presents the concept of bridging the gap between diagnostic
      images and image-assisted surgical treatment through the development of a one
      stop multimedia electronic patient record (ePR) system that manages and
      distributes the real-time multimodality imaging and informatics data that assists
      the surgeon during all clinical phases of the operation from planning Intra-Op to
      post-care follow-up. We present the concept of this multimedia ePR for surgery by
      first focusing on image-assisted minimally invasive spinal surgery as a clinical
      application. METHODS: Three clinical phases of minimally invasive spinal surgery
      workflow in Pre-Op, Intra-Op, and Post-Op are discussed. The ePR architecture was
      developed based on the three-phased workflow, which includes the Pre-Op, Intra
      Op, and Post-Op modules and four components comprising of the input integration
      unit, fault-tolerant gateway server, fault-tolerant ePR server, and the
      visualization and display. A prototype was built and deployed to a minimally
      invasive spinal surgery clinical site with user training and support for daily
      use. SUMMARY: A step-by-step approach was introduced to develop a multimedia ePR
      system for imaging-assisted minimally invasive spinal surgery that includes
      images, clinical forms, waveforms, and textual data for planning the surgery, two
      real-time imaging techniques (digital fluoroscopic, DF) and endoscope video
      images (Endo), and more than half a dozen live vital signs of the patient during
      surgery. Clinical implementation experiences and challenges were also discussed.

PMID- 20033508
TI  - An integrated approach for reconstructing a surface model of the proximal femur
      from sparse input data and a multi-resolution point distribution model: an in
      vitro study.
AB  - BACKGROUND: Accurate reconstruction of a patient-specific surface model of the
      proximal femur from preoperatively or intraoperatively available sparse data
      plays an important role in planning and supporting various computer-assisted
      surgical procedures. METHODS: In this paper, we present an integrated approach
      using a multi-resolution point distribution model (MR-PDM) to reconstruct a
      patient-specific surface model of the proximal femur from sparse input data,
      which may consist of sparse point data or a limited number of calibrated X-ray
      images. Depending on the modality of the input data, our approach chooses
      different PDMs. When 3D sparse points are used, which may be obtained
      intraoperatively via a pointer-based digitization or from a calibrated
      ultrasound, a fine level point distribution model (FL-PDM) is used in the
      reconstruction process. In contrast, when calibrated X-ray images are used, which
      may be obtained preoperatively or intraoperatively, a coarse level point
      distribution model (CL-PDM) will be used. RESULTS: The present approach was
      verified on 31 femurs. Three different types of input data, i.e., sparse points,
      calibrated fluoroscopic images, and calibrated X-ray radiographs, were used in
      our experiments to reconstruct a surface model of the associated bone. Our
      experimental results demonstrate promising accuracy of the present approach.
      CONCLUSIONS: A multi-resolution point distribution model facilitate the
      reconstruction of a patient-specific surface model of the proximal femur from
      sparse input data.

PMID- 20033509
TI  - Automated pancreas segmentation from three-dimensional contrast-enhanced computed
      tomography.
AB  - PURPOSE: We propose an automated pancreas segmentation algorithm from contrast
      enhanced multiphase computed tomography (CT) and verify its effectiveness in
      segmentation. METHODS: The algorithm is characterized by three unique ideas.
      First, a two-stage segmentation strategy with spatial standardization of pancreas
      was employed to reduce variations in the pancreas shape and location. Second,
      patient- specific probabilistic atlas guided segmentation was developed to cope
      with the remaining variability in shape and location. Finally, a classifier
      ensemble was incorporated to refine the rough segmentation results. RESULTS: The
      effectiveness of the proposed algorithm was validated with 20 unknown CT volumes,
      as well as three on-site CT volumes distributed in a competition of pancreas
      segmentation algorithms. The experimental results indicated that the segmentation
      performance was enhanced by the proposed algorithm, and the Jaccard index between
      an extracted pancreas and a true one was 57.9%. CONCLUSIONS: This study verified
      the effectiveness of two-stage segmentation with spatial standardization of
      pancreas in delineating the pancreas region, patient-specific probabilistic atlas
      guided segmentation in reducing false negatives, and a classifier ensemble in
      boosting segmentation performance.

PMID- 20033510
TI  - Path generator control system and virtual compliance calculator for maxillofacial
      massage robots.
AB  - PURPOSE: Oral disorders such as temporomandibular joint disorders (TMD) and dry
      mouth are common and often require treatment. Maxillofacial massage is used as a
      complementary and alternative therapy for these disorders. We developed an oral
      rehabilitation robot that massages the maxillofacial tissues for this purpose. In
      this paper, we propose a control system for oral rehabilitation robots. METHOD:
      The control system consists of a massage path generator, virtual compliance
      calculator, and inverse kinematics calculator. The massage path generator
      computes a target massage path based on a human head model obtained from a
      reference MRI image of an adult male. The head model includes the shape and
      elastic modulus of each component, all of which were obtained experimentally.
      Virtual compliance control is used to control manipulators with position servo
      actuators. The manipulators, which have a force sensor at their end-effectors,
      move actively in the direction of the external force applied to their sensors via
      virtual compliance control. We implemented this control in WAO-1, our first
      prototype oral rehabilitation robot. RESULTS: WAO-1 provided massage to three
      adult male subjects with and without virtual compliance control. One of the
      subjects was the adult male whose MRI image was used to synthesize the head model
      in the massage path generator. Without virtual compliance control, the actual
      massage force was greater than the target massage force, while that with virtual
      compliance control was less than the target massage force. Furthermore, with
      virtual compliance control, the massage paths conformed to the head shape of each
      patient. CONCLUSION: Implementation of virtual compliance control in the WAO-1
      massage robot is feasible and useful for implementation of safe and potentially
      effective maxillofacial massage therapy.

PMID- 20033511
TI  - Visualization of osseointegration of maxilla and mandible dental implants.
AB  - PURPOSE: We present a new, hybrid visualization method that can assist in
      assessing the degree of osseointegration of dental implants. METHOD: The method
      is based on radiographic imaging, three-dimensional (3-D) volume reconstruction,
      and color coding of bone density. It provides both a 3-D image of the titanium
      implant and the implant site, and a two-dimensional (2-D) profile of the lingual
      and buccal sides of the implant, exposing possible weaknesses in the supporting
      bone structure. The visualization procedure described here consists of 2-D cross
      sectional CT imaging, 3-D gradient-based hardware-accelerated volume rendering
      using 3-D texture mapping, implant site extraction using 3-D selection of a 2-D
      cross-sectional, tri-linearly interpolated 2-D image, computation of a bone
      density profile and line integral along the implant, and 3-D hybrid rendering of
      the implant site and the derived bone density information in its anatomical
      context. This method has been demonstrated to be successful in enabling the
      mapping of information derived from virtual bone density measurements onto a
      geometric object, thus providing the necessary information to relate other
      information from mechanical testing or simulations to the respective site.
      RESULTS: A high-resolution scan of a cadaver was used as a reference data set.
      The hybrid view, a combination of 2-D density profile and 3-D color-coded density
      rendering, turned out to be very intuitive and easy to interpret. The 2-D view
      was also useful for relating standard 2-D X-ray imaging with enhanced 3-D imaging
      of bone density. On top of this, our image-based method was used for cross
      validation of a mechanical testing method. It turned out that the results from
      mechanical testing of osseointegration were very well correlated with the results
      from our image-based 2-D and 3-D methods. CONCLUSIONS: Since these two methods
      work in completely different ways (mechanical vs. radiographic) and the results
      came out are the same, the results provide evidence that both methods for
      assessing the degree and location of osseointegration are valid. Further studies
      using additional scans on living subjects will be conducted to provide additional
      evidence. Cost-efficient X-ray imaging can be used to replace the simulated
      implant-aligned 2-D X-ray views that were obtained from a 3-D scan.

PMID- 20033512
TI  - Hybrid 3D pregnant woman and fetus modeling from medical imaging for dosimetry
      studies.
AB  - PURPOSE: Numerical simulations studying the interactions between radiations and
      biological tissues require the use of three-dimensional models of the human
      anatomy at various ages and in various positions. Several detailed and flexible
      models exist for adults and children and have been extensively used for
      dosimetry. On the other hand, progress of simulation studies focusing on pregnant
      women and the fetus have been limited by the fact that only a small number of
      models exist with rather coarse anatomical details and a poor representation of
      the anatomical variability of the fetus shape and its position over the entire
      gestation. METHODS: In this paper, we propose a new computational framework to
      generate 3D hybrid models of pregnant women, composed of fetus shapes segmented
      from medical images and a generic maternal body envelope representing a synthetic
      woman scaled to the dimension of the uterus. The computational framework includes
      the following tasks: image segmentation, contour regularization, mesh-based
      surface reconstruction, and model integration. RESULTS: A series of models was
      created to represent pregnant women at different gestational stages and with the
      fetus in different positions, all including detailed tissues of the fetus and the
      utero-fetal unit, which play an important role in dosimetry. These models were
      anatomically validated by clinical obstetricians and radiologists who verified
      the accuracy and representativeness of the anatomical details, and the
      positioning of the fetus inside the maternal body. CONCLUSION: The computational
      framework enables the creation of detailed, realistic, and representative fetus
      models from medical images, directly exploitable for dosimetry simulations.

PMID- 20033513
TI  - Software for hepatic vessel classification: feasibility study for virtual
      surgery.
AB  - PURPOSE: The detection and classification of hepatic vessels in diagnostic images
      are essential for hepatic pre-surgery planning. Our team has developed a tool for
      classification, analysis, and 3D reconstruction of the hepatic and portal
      systems. METHODS: Our software first extracts a graphic representation of a set
      of connected voxels, representing both systems. It then calculates two binary
      volumes representing the main part of the two venous systems. Finally, it
      combines these results to obtain the correct vessel classification. RESULTS:
      Segmentation steps are semi-automatic and require about 40 min to complete.
      Schematization and classification steps are automatic and require about 17 min
      for results. CONCLUSION: The software provides a correct and detailed
      reconstruction even where pathologies have caused morphological and geometrical
      variations in the vessels. The time required for the entire procedure is
      compatible with clinical requirements, providing an efficient tool for diagnosis
      and surgical planning.

PMID- 20033514
TI  - Computer simulation of vertebral artery occlusion in endovascular procedures.
AB  - OBJECTIVE: The aim of this work is to establish a computational pipeline for the
      simulation of blood flow in vasculatures and apply this pipeline to endovascular
      interventional scenarios, e.g. angioplasty in vertebral arteries. METHODS: A
      patient-specific supra-aortal vasculature is digitized from a 3D CT angiography
      image. By coupling a reduced formulation of the governing Navier-Stokes equations
      with a wall constitutive equation we are able to solve the transient flow in
      elastic vessels. By further incorporating a bifurcation model the blood flow
      across vascular branches can be evaluated, thus flow in a large vasculature can
      be modeled. Vascular diseases are simulated by modifying the arterial tree
      configurations, e.g. the effective diameters, schematic connectivity, etc.
      Occlusion in an artery is simulated by removing that artery from the arterial
      tree. RESULTS: It takes about 2 min per cardiac cycle to compute blood flow in an
      arterial tree consisting of 38 vessels and 18 bifurcations on a laptop PC. The
      simulation results show that blood supply in the posterior region is compensated
      from the contralateral vertebral artery and the anterior cerebral arteries if one
      of the vertebral arteries is occluded. CONCLUSION: The computational pipeline is
      computationally efficient and can capture main flow patterns at any point in the
      arterial tree. With further improvement it can serve as a powerful tool for the
      haemodynamic analysis in patient-specific vascular structures.

PMID- 20033515
TI  - COTS technologies for telemedicine applications.
AB  - PURPOSE: To demonstrate a simple low-cost system for tele-echocardiology, focused
      on paediatric cardiology applications. METHODS: The system was realized using
      open-source software and COTS technologies. It is based on the transmission of
      two simultaneous video streams, obtained by direct digitization of the output of
      an ultrasound machine and by a netcam showing the examination that is taking
      place. These streams are then embedded into a web page so they are accessible,
      together with basic video controls, via a standard web browser. The system can
      also record video streams on a server for further use. RESULTS: The system was
      tested on a small group of neonatal cases with suspected cardiopathies for a
      preliminary assessment of its features and diagnostic capabilities. Both the
      clinical and technological results were encouraging and are leading the way for
      further experimentation. CONCLUSIONS: The presented system can transfer clinical
      images and videos in an efficient way and in real time. It can be used in the
      same hospital to support internal consultancy requests, in remote areas using
      Internet connections and for didactic purposes using low cost COTS appliances and
      simple interfaces for end users. The solution proposed can be extended to control
      different medical appliances in those remote hospitals.

PMID- 20033516
TI  - Applicability of DICOM structured reporting for the standardized exchange of
      implantation plans.
AB  - PURPOSE: Today's operating room is equipped with different devices supporting the
      surgeon. Due to the lack of common interfaces between devices, an integrated
      support of the surgical workflow is missing. In the field of implantation, a
      smooth exchange of preoperatively planned data between devices is of great
      interest. Additionally, the availability of standardized preoperative data would
      facilitate the documentation, especially with regard to Electronic Health
      Records. METHODS: To analyze whether DICOM Structured Reporting can be the basis
      for a standardized digital human- and machine-readable implantation plan, we
      derived all requirements for such a document. Therefore, we examined the
      conventional implantation plan and future applications of the digital plan.
      RESULTS: In this paper, we propose to use the mechanisms introduced by DICOM
      Structured Reporting as storage and communication infrastructure for implantation
      plans in the surgical domain. DICOM Structured Reporting complies with all
      requirements of our analysis. Additionally, we introduce a first draft of a
      standardized implantation plan structure. CONCLUSIONS: A standardized digital
      implantation plan based on the DICOM Structured Report has the potential to
      overcome current integration problems in the OR and to facilitate new
      applications.

PMID- 20033517
TI  - DLR MiroSurge: a versatile system for research in endoscopic telesurgery.
AB  - PURPOSE: Research on surgical robotics demands systems for evaluating scientific
      approaches. Such systems can be divided into dedicated and versatile systems.
      Dedicated systems are designed for a single surgical task or technique, whereas
      versatile systems are designed to be expandable and useful in multiple surgical
      applications. Versatile systems are often based on industrial robots, though, and
      because of this, are hardly suitable for close contact with humans. METHOD: To
      achieve a high degree of versatility the Miro robotic surgery platform (MRSP)
      consists of versatile components, dedicated front-ends towards surgery and
      configurable interfaces for the surgeon. RESULTS: This paper presents MiroSurge,
      a configuration of the MRSP that allows for bimanual endoscopic telesurgery with
      force feedback. CONCLUSIONS: While the components of the MiroSurge system are
      shown to fulfil the rigid design requirements for robotic telesurgery with force
      feedback, the system remains versatile, which is supposed to be a key issue for
      the further development and optimisation.

PMID- 20033518
TI  - An automated insertion tool for cochlear implants: another step towards
      atraumatic cochlear implant surgery.
AB  - PURPOSE: Atraumatic electrode insertion has been identified to be a crucial step
      for the preservation of residual hearing abilities, which allows hybrid electro
      acoustic stimulation (EAS). The authors propose a tool for automation of the
      insertion process to achieve this. METHODS: General benefits as well as concept
      and design of an automated insertion tool are presented. Thirty insertions of
      Nucleus 24 Contour Advance Practice Electrodes in an artificial scala tympani
      model as well as 20 insertions in a human cochlea specimen were performed using
      the tool, implementing the AOS technique. For both studies, the achieved
      insertion depth angle was evaluated by photographic or X-ray documentation.
      RESULTS: The mean achieved insertion depth angle was 410 degrees for the
      lubricated model and 330 degrees for the human cochlea specimen. CONCLUSION: The
      automated insertion tool has proven its capability to perform electrode
      insertions with final insertion depth angles within the target range of a
      standard cochlear implant surgery. Additionally, to the knowledge of the authors,
      it represents the only possibility to automatically insert cochlear implant
      electrodes via minimally invasive approaches.

PMID- 20033519
TI  - Illustrative visualization of 3D planning models for augmented reality in liver
      surgery.
AB  - PURPOSE: Augmented reality (AR) obtains increasing acceptance in the operating
      room. However, a meaningful augmentation of the surgical view with a 3D
      visualization of planning data which allows reliable comparisons of distances and
      spatial relations is still an open request. METHODS: We introduce methods for
      intraoperative visualization of 3D planning models which extend illustrative
      rendering and AR techniques. We aim to reduce visual complexity of 3D planning
      models and accentuate spatial relations between relevant objects. The main
      contribution of our work is an advanced silhouette algorithm for 3D planning
      models (distance-encoding silhouettes) combined with procedural textures
      (distance-encoding surfaces). In addition, we present a method for illustrative
      visualization of resection surfaces. RESULTS: The developed algorithms have been
      embedded into a clinical prototype that has been evaluated in the operating room.
      To verify the expressiveness of our illustration methods, we performed a user
      study under controlled conditions. The study revealed a clear advantage in
      distance assessment with the proposed illustrative approach in comparison to
      classical rendering techniques. CONCLUSION: The presented illustration methods
      are beneficial for distance assessment in surgical AR. To increase the safety of
      interventions with the proposed approach, the reduction of inaccuracies in
      tracking and registration is a subject of our current research.

PMID- 20033520
TI  - Planning and simulation of microsurgical laser bone ablation.
AB  - PURPOSE: Laser ablation of hard tissue is not completely understood until now and
      not modeled for computer-assisted microsurgery. A precise planning and simulation
      is an essential step toward the usage of microsurgical laser bone ablation in the
      operating room. METHODS: Planning the volume for laser bone ablation is based on
      geometrical definitions. Shape and volume of the removed bone by single laser
      pulses were measured with a confocal microscope for modeling the microsurgical
      ablation. To remove the planned volume and to achieve smooth surfaces, a
      simulation of the laser pulse distribution is developed. RESULTS: The confocal
      measurements show a clear dependency from laser energy and resulting depth. Two
      dimensional Gaussian functions are fitting in these craters. Exemplarily three
      ablation layers were planned, simulated, executed and verified. CONCLUSIONS: To
      model laser bone ablation in microsurgery the volume and shape of each laser
      pulse should be known and considered in the process of ablation planning and
      simulation.

PMID- 20033521
TI  - Direct visualization of fiber information by coherence.
AB  - PURPOSE: The structure of fiber tracts in DT-MRI data presents a challenging
      problem for visualization and analysis. We derive visualization of such traces
      from a local coherence measure and achieve much improved visual segmentation.
      METHODS: We introduce a coherence measure defined for fiber tracts. This
      quantitative assessment is based on infinitesimal deviations of neighboring
      tracts and allows identification and segmentation of coherent fiber regions. We
      use a hardware-accelerated implementation to achieve interactive visualization on
      slices and provide several approaches to visualize coherence information.
      Furthermore, we enhance existing techniques by combining them with coherence.
      RESULTS: We demonstrate our method on both a canine heart, where the myocardial
      structure is visualized, and a human brain, where we achieve detailed
      visualization of major and minor fiber bundles in a quality similar to and
      exceeding fiber clustering approaches. CONCLUSIONS: Our approach allows detailed
      and fast visualization of important anatomical structures in DT-MRI data sets.

PMID- 20033522
TI  - Automated insertion of preformed cochlear implant electrodes: evaluation of
      curling behaviour and insertion forces on an artificial cochlear model.
AB  - PURPOSE: As a substantial part of our concept of a minimally invasive cochlear
      implant (CI) surgery, we developed an automated insertion tool. Studies on an
      artificial scala tympani model were performed in order to evaluate force
      application when using the insertion tool. METHODS: Contour electrodes were
      automatically inserted into a transparent cochlea model in Advance Off-Stylet
      technique. Occurring forces were measured by the use of a load cell and
      correlated with observed intracochlear movement of the electrode carriers.
      RESULTS: Mean insertion forces were measured up to 20 mN comparable to previous
      studies on temporal bones. The most influencing factor is the implant's 2D
      curling behaviour in comparison to the 3D helical shape of the cochlea.
      CONCLUSION: The study confirms the functionality and reliability of the automated
      insertion tool for insertion of preformed CI. Improved insertion strategies
      considering patient-specific anatomy become possible.

PMID- 20033523
TI  - Simultaneous cutting of coupled tetrahedral and triangulated meshes and its
      application in orbital reconstruction.
AB  - INTRODUCTION: Recently, advances in imaging techniques for diagnostics and
      associated technologies have led to an improved preoperative planning for
      craniomaxillofacial surgeons. In particular, the application of navigation-aided
      procedures for orbital reconstruction has proved to be essential. Preforming
      orbital implants for orbital floor reconstruction and determining overcorrection
      with regard to the orbital floor reconstruction could be achieved using
      preoperative planning. It has turned out that the computation of soft tissue cuts
      is an essential prerequisite for the realistic placement of implants. METHODS: We
      propose a simulation framework that allows for the static and dynamic cutting of
      soft and hard tissue representations. The framework comprises components to model
      tissue deformation, cutting of tissue and interaction between the physical
      bodies. Furthermore, volume and surface representations are decoupled which
      allows for an independent scaling in the complexity of the representations and,
      therefore, in the simulation and visualisation performance. In contrast to many
      other cutting approaches, our algorithm handles both representations
      simultaneously. CONCLUSION: The framework is used to simulate the realistic
      insertion of a preformed orbital implant model through the soft tissue cut and
      the prediction of the postoperative eye bulb position. Experiments show that the
      framework can be used to determine overcorrection and to preform orbital
      implants.

PMID- 20033524
TI  - RepliExplore: coupling physical and virtual anatomy models.
AB  - PURPOSE: We present a system which co-registers physical anatomy models with
      virtual three-dimensional (3D) representations. Interactions performed on the
      physical model by means of a 3D pointing device are directly reflected on its
      virtual counterpart. Complex anatomical information integrated into the virtual
      model thus becomes accessible through the physical interface in a simple and
      intuitive manner. METHODS: Using an optical tracking system, we implemented and
      tested a reference application that includes several tools for the exploration
      and quantification of anatomical models. We theoretically evaluated the accuracy
      of the landmark-based registration for different landmark configurations.
      RESULTS: Physicians and computer scientists found the system simple to learn and
      intuitive to use. By optimizing landmark configurations, the accuracy could be
      significantly increased, particularly for scenarios in which only selected
      regions required higher accuracy. CONCLUSIONS: Physical anatomical models can
      benefit from the combination with a virtual counterpart in several ways.
      Applications include anatomical education and the study of patient-individual
      organ models. Optimizing the registration landmark configuration for specific
      applications can lower the accuracy requirements for the tracking system.

PMID- 20033525
TI  - A probabilistic framework for freehand 3D ultrasound reconstruction applied to
      catheter ablation guidance in the left atrium.
AB  - INTRODUCTION: The catheter ablation procedure is a minimally invasive surgery
      used to treat atrial fibrillation. Difficulty visualizing the catheter inside the
      left atrium anatomy has led to lengthy procedure times and limited success rates.
      In this paper, we present a set of algorithms for reconstructing 3D ultrasound
      data of the left atrium in real-time, with an emphasis on automatic tissue
      classification for improved clarity surrounding regions of interest. METHODS:
      Using an intracardiac echo (ICE) ultrasound catheter, we collect 2D-ICE images of
      a left atrium phantom from multiple configurations and iteratively compound the
      acquired data into a 3D-ICE volume. We introduce two new methods for compounding
      overlapping US data-occupancy-likelihood and response-grid compounding-which
      automatically classify voxels as "occupied" or "clear," and mitigate
      reconstruction artifacts caused by signal dropout. Finally, we use the results of
      an ICE-to-CT registration algorithm to devise a response-likelihood weighting
      scheme, which assigns weights to US signals based on the likelihood that they
      correspond to tissue-reflections. RESULTS: Our algorithms successfully
      reconstruct a 3D-ICE volume of the left atrium with voxels classified as
      "occupied" or "clear," even within difficult-to-image regions like the pulmonary
      vein openings. We are robust to dropout artifact that plagues a subset of the 2D
      ICE images, and our weighting scheme assists in filtering out spurious data
      attributed to ghost-signals from multi-path reflections. By automatically
      classifying tissue, our algorithm precludes the need for thresholding, a process
      that is difficult to automate without subjective input. Our hope is to use this
      result towards developing 3D ultrasound segmentation algorithms in the future.

PMID- 20033526
TI  - Forecasting respiratory motion with accurate online support vector regression
      (SVRpred).
AB  - OBJECT: To accurately deliver radiation in image-guided robotic radiosurgery,
      highly precise prediction algorithms are required. A new prediction method is
      presented and evaluated. MATERIALS AND METHODS: SVRpred, a new prediction method
      based on support vector regression (SVR), has been developed and tested. Computer
      generated data mimicking human respiratory motion with a prediction horizon of
      150 ms was used for lab tests. The algorithm was subsequently evaluated on a
      respiratory motion signal recorded during actual radiosurgical treatment using
      the CyberKnife. The algorithm's performance was compared to the MULIN prediction
      methods and Wavelet-based multi scale autoregression (wLMS). RESULTS: The SVRpred
      algorithm clearly outperformed both the MULIN and the wLMS algorithms on both
      real (by 15 and 16 percentage points, respectively) and noise-corrupted simulated
      data (by 13 and 48 percentage points, respectively). Only on noise-free
      artificial data, the SVRpred algorithm did perform as well as the MULIN
      algorithms but not as well as the wLMS algorithm. CONCLUSION: This new algorithm
      is a feasible tool for the prediction of human respiratory motion signals
      significantly outperforming previous algorithms. The only drawback is the high
      computational complexity and the resulting slow prediction speed. High
      performance computers will be needed to use the algorithm in live prediction of
      signals sampled at a high resolution.

PMID- 20033527
TI  - Pulmonary blood flow evaluation using a dynamic flat-panel detector: feasibility
      study with pulmonary diseases.
AB  - PURPOSE: Pulmonary ventilation and circulation dynamics are reflected on
      fluoroscopic images as changes in X-ray translucency. The purpose of this study
      was to investigate the feasibility of non-contrast functional imaging using a
      dynamic flat-panel detector (FPD). METHODS: Dynamic chest radiographs of 20
      subjects (abnormal, n = 12; normal, n = 8) were obtained using the FPD system.
      Image analysis was performed to get qualitative perfusion mapping image; first,
      focal pixel value was defined. Second, lung area was determined and pulmonary
      hilar areas were eliminated. Third, one cardiac cycle was determined in each of
      the cases. Finally, total changes in pixel values during one cardiac cycle were
      calculated and their distributions were visualized with mapping on the original
      image. They were compared with the findings of lung perfusion scintigraphy.
      RESULTS: In all normal controls, the total changes in pixel value in one cardiac
      cycle decreased from the hilar region to the peripheral region of the lung with
      left-right symmetric distribution. In contrast, in many abnormal cases, pulmonary
      blood flow disorder was indicated as a reduction of changes in pixel values on a
      mapping image. The findings of mapping image coincided with those of lung
      perfusion scintigraphy. CONCLUSIONS: Dynamic chest radiography using an FPD
      system with computer analysis is expected to be a new type of functional imaging,
      which provides pulmonary blood flow distribution additionally.

PMID- 20033528
TI  - Comparison of diagnostic quality and accuracy in color-coded versus gray-scale
      DCE-MR imaging display.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic value and tumor
      vascular display properties (microcirculation) of two different functional MRI
      post-processing and display (color and gray-scale display) techniques used in
      oncology. MATERIALS AND METHODS: The study protocol was approved by the IRB and
      written informed consent was obtained from all patients. 38 dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) data sets of patients with
      malignant pleural-mesothelioma were acquired and post-processed. DCE-MRI was
      performed at 1.5 tesla with a T1-weighted 2D gradient-echo-sequence (TR 7.0 ms,
      TE 3.9 ms, 15 axial slices, 22 sequential repetitions), prior and during
      chemotherapy. Subtracting first image of contrast-enhanced-dynamic series from
      the last, produced gray-scale images. Color images were produced using a
      pharmacokinetic two-compartment model. Eight raters, blinded to diagnosis, by
      visual assessment of post-processed images evaluated both diagnostic quality of
      the images and vasculature of the tumor using a rating scale ranging from -5 to
      +5. The scores for vasculature were assessed by correlating with the maximum
      amplitude of the total-tumor-ROI for accuracy. RESULTS: Color coded images were
      rated as significantly higher in diagnostic quality and tumor vascular score than
      gray-scale images (p < 0.001, 0.005). ROI signal amplitude analysis and vascular
      ratings on color coded images were better correlated compared to gray-scale
      images rating (p < 0.05). CONCLUSION: Color coded images were shown to have
      higher diagnostic quality and accuracy with respect to tumor vasculature in DCE
      MRI, therefore their implementation in clinical assessment and follow-up should
      be considered for wider application.

PMID- 20033529
TI  - Intensity-based elastic registration incorporating anisotropic landmark errors
      and rotational information.
AB  - PURPOSE: Thin-plate splines (TPS) represent an effective tool for estimating the
      deformation that warps one set of landmarks to another based on the physical
      equivalent of thin metal sheets. In the original formulation, data used to
      estimate the deformation field are restricted to landmark locations only and thus
      does not allow to incorporate information about the rotation of the image around
      the landmark. It furthermore assumes that landmark positions are known exactly
      which is not the case in real world applications. These localization inaccuracies
      are propagated to the entire deformation field as each landmark has a global
      influence. We propose to use a TPS approximation method that incorporates
      anisotropic landmark errors and rotational information and integrate it into a
      hierarchical elastic registration framework (HERA). The improvement of the
      registration performance has been evaluated. METHODS: The proposed TPS
      approximation scheme integrates anisotropic landmark errors with rotational
      information of the landmarks. The anisotropic landmark errors are represented by
      their covariance matrices estimated directly from the image data as a minimal
      stochastic localization error, i.e. the Cramer-Rao bound. The rotational
      attribute of each landmark is characterized by an additional angular landmark,
      thus doubling the number of landmarks in the TPS model. This allows the TPS
      approximation to better cope up with local deformations. RESULTS: We integrated
      the proposed TPS approach into the HERA registration framework and applied it to
      register 161 image pairs from a digital mammogram database. Experiments showed
      that the mean squared error using the proposed TPS approximation was superior to
      pure TPS interpolation. On artificially deformed breast images HERA, with the
      proposed TPS approximation, performed significantly better than the state-of-the
      art registration method presented by Rueckert. CONCLUSION: The TPS approximation
      approach proposed in this publication allows to incorporate anisotropic landmark
      errors as well as rotational information. The integration of the method into an
      intensity-based hierarchical non-rigid registration framework is straightforward
      and improved the registration quality significantly.

PMID- 20033530
TI  - Interactive determination of robust safety margins for oncologic liver surgery.
AB  - OBJECTIVE: Complex oncologic interventions in the liver require an extensive and
      careful preoperative analysis. Particularly the achievement of an optimal safety
      margin around tumors remains a difficult task for surgeons. METHODS: We present
      new methods for evaluating different safety margins and their effect on the
      associated interruption of vascular supply or drainage. The characteristic of
      vascular risk distributions can be evaluated in real-time by exploiting
      precomputed safety maps that provide a volume curve for each vascular system. By
      applying fast visualization methods in 3D it is possible to assist the surgeon in
      the determination of a tumor-free safety margin while preserving sufficient vital
      hepatic parenchyma. The combination of risk analysis from different vascular
      systems and their sensitivity is considered. RESULTS: We provide physicians with
      a novel computer-aided planning tool that allows for interactive determination of
      safety margins in real-time. The planning tool integrates smoothly into the
      preoperative workflow. Preliminary evaluations confirm that the width of safety
      margins can be determined more precisely, which may affect the proposed resection
      strategy. CONCLUSION: Our new methods provide interactive feedback and support
      for decision making during the preoperative planning stage and thus might
      potentially improve the outcome of surgical interventions.

PMID- 20033531
TI  - A robot-guided minimally invasive approach for cochlear implant surgery:
      preliminary results of a temporal bone study.
AB  - PURPOSE: The aim of this study was to create an access canal to the inner ear, by
      drilling, and perform the cochleostomy for cochlear implant surgery using robot
      guidance. METHODS: A robot, a surgical drill and an Image-Guided Surgery (IGS)
      system were combined in a closed-loop setup. Ten temporal bones were scanned at
      the planning stages of the procedure. The robot guided the drill along the
      preplanned trajectory and created the approach. Postoperative scans were
      obtained. RESULTS: The cochleostomy was performed completely in nine out of ten
      cases. This did not prove possible for one of the specimens, the target site
      selected being in too superficial a location in relation to the round window. No
      violation of the facial nerve took place, although the chorda tympani nerve was
      violated in one case and the stapes in two. It was obvious during preoperative
      planning that these structures would be violated, but this was accepted in order
      to maintain a safety margin from the facial nerve. No other unforeseen damage
      occurred. CONCLUSIONS: This preliminary study suggests that robot-guided drilling
      of a minimally invasive approach to the cochlea might be feasible, but further
      improvements are necessary before any clinical application becomes possible.
      Where the width of the facial recess is less than 2.5 mm, the chorda tympani
      nerve and the ossicles are at risk.

PMID- 20033532
TI  - Evaluation of a navigated and power controlled milling system "navigated control
      spine" for spinal surgery.
AB  - PURPOSE: The aim of this work was the evaluation of a navigated and power
      controlled milling system for spine surgery (navigated control spine). The
      navigation is based on a set of intraoperatively taken fluoroscopic images from
      different angles. A manually planned workspace limits the power of the mill and
      assures a higher automatisation degree than any other established navigation
      system for spine surgery. METHODS: Both a technical study in workspace planning
      from fluoroscopic images and a milling study on a spine phantom were performed
      with participants with different level of knowledge of spinal surgery. RESULTS:
      In the region of interest the workspace planning could be performed with a
      maximum excess of 1.40 mm for surgeons. In the study performing the milling of a
      standardised workspace the remnant bone after milling had a mean difference from
      the planned workspace margin of 1.96-2.12 mm in the region of most interest.
      Accurate handling of the mill still required a certain level of medical knowledge
      and experience. In both studies the time needed for application of the system
      proved acceptable for clinical purposes. DISCUSSION: This concept of navigated
      and power controlled spinal surgery has proven feasible in an experimental study.
      This navigation system seems therefore promising for clinical application.

PMID- 20033533
TI  - Clinical evaluation of angiographic multiple-view 3D reconstruction.
AB  - PURPOSE: Endovascular treatment of stroke, a leading cause of death in the United
      States, involves guidance of devices to the intervention site often through
      tortuous vessels. Typically, these interventions are performed under two-
      dimensional (2D) fluoroscopy. To facilitate these procedures, we developed and
      previously presented a multiple-view self-calibration method involving two steps:
      (1) calibration of the imaging geometry, and (2) reconstruction of the 3D vessel
      centerline. Only those 2D angiograms obtained during the procedure are used for
      reconstruction. In this manuscript, we evaluate this technique on a large set
      (117 cases) of clinical data obtained over a 12-month period. METHODS: We
      evaluated the technique using (1) the RMS difference between the calculated 3D
      centerlines and the average centerline (before and after application of our
      method), (2) the difference between the projected 3D centerlines and the 2D
      indicated centerlines, (3) the translations and rotations calculated by our
      technique, and (4) intra- and inter-user variations. RESULTS: Our approach (1)
      reduces the RMS 3D differences by a factor of 10, (2) increases the number of
      projected 3D centerline points lying within 1 mm of the indicated 2D centerline
      points by over a factor of 2 (from 28 to 71%), (3) provides an assessment of the
      variations in the gantry geometry as provided by the imaging system, and (4) is
      insensitive to user variations in indication (<1 mm differences in 3D are seen).
      CONCLUSIONS: These results indicate that this technique will provide more
      reliable vessel centerlines in the clinical setting without requiring additional
      acquisitions or increasing dose to the patient.

PMID- 20033535
TI  - CARS (Computer Assisted Radiology and Surgery) 2009. Abstracts of the 23rd
      International Congress and Exhibition. Berlin, Germany. June 23-27, 2009.

PMID- 20033534
TI  - Radiology information system: a workflow-based approach.
AB  - PURPOSE: Introducing workflow management technology in healthcare seems to be
      prospective in dealing with the problem that the current healthcare Information
      Systems cannot provide sufficient support for the process management, although
      several challenges still exist. The purpose of this paper is to study the method
      of developing workflow-based information system in radiology department as a use
      case. METHOD: First, a workflow model of typical radiology process was
      established. Second, based on the model, the system could be designed and
      implemented as a group of loosely coupled components. Each component corresponded
      to one task in the process and could be assembled by the workflow management
      system. The legacy systems could be taken as special components, which also
      corresponded to the tasks and were integrated through transferring non-work- flow
      aware interfaces to the standard ones. Finally, a workflow dashboard was designed
      and implemented to provide an integral view of radiology processes. RESULT: The
      workflow-based Radiology Information System was deployed in the radiology
      department of Zhejiang Chinese Medicine Hospital in China. The results showed
      that it could be adjusted flexibly in response to the needs of changing process,
      and enhance the process management in the department. It can also provide a more
      workflow-aware integration method, comparing with other methods such as IHE-based
      ones. CONCLUSION: The workflow-based approach is a new method of developing
      radiology information system with more flexibility, more functionalities of
      process management and more workflow-aware integration. The work of this paper is
      an initial endeavor for introducing workflow management technology in healthcare.

PMID- 20033578
TI  - Robot-assisted catheter manipulation for intracardiac navigation.
AB  - OBJECTIVE: Manual navigation of intracardiac steerable catheters is inaccurate,
      requires dexterity for efficient manipulation of the catheter, and exposes the
      interventionalist to ionizing radiation. The objective of this research is to
      develop a system that replaces the interventionalists's hands in catheter
      manipulation for accurate and semi-automatic tele-navigation of catheters.
      METHODS: Based on a proposed kinematic model for the distal shaft of the
      catheter, a system has been developed for assisted navigation of intracardiac
      catheters. When the distal shaft of the catheter lies inside a cardiac chamber, a
      robotic apparatus is utilized for automatic steering of the catheter tip to reach
      designated targets within the chamber. RESULTS: The catheter modeling was
      validated through the experiments on three swine. The robotic system could
      navigate the catheter tip to designated targets with a mean distance of 6.53 mm
      from the target. CONCLUSION: Preliminary in vivo studies demonstrate the feasible
      application of the system in catheter navigation and the validity of catheter
      modeling and control strategies.

PMID- 20033579
TI  - Integration of computer-aided diagnosis/detection (CAD) results in a PACS
      environment using CAD-PACS toolkit and DICOM SR.
AB  - PURPOSE: Picture Archiving and Communication System (PACS) is a mature technology
      in health care delivery for daily clinical imaging service and data management.
      Computer-aided detection and diagnosis (CAD) utilizes computer methods to obtain
      quantitative measurements from medical images and clinical information to assist
      clinicians to assess a patient's clinical state more objectively. CAD needs image
      input and related information from PACS to improve its accuracy; and PACS
      benefits from CAD results online and available at the PACS workstation as a
      second reader to assist physicians in the decision making process. Currently,
      these two technologies remain as two separate independent systems with only
      minimal system integration. This paper describes a universal method to integrate
      CAD results with PACS in its daily clinical environment. METHODS: The method is
      based on Health Level 7 (HL7) and Digital imaging and communications in medicine
      (DICOM) standards, and Integrating the Healthcare Enterprise (IHE) workflow
      profiles. In addition, the integration method is Health Insurance Portability and
      Accountability Act (HIPAA) compliant. SUMMARY: The paper presents (1) the
      clinical value and advantages of integrating CAD results in a PACS environment,
      (2) DICOM Structured Reporting formats and some important IHE workflow profiles
      utilized in the system integration, (3) the methodology using the CAD-PACS
      integration toolkit, and (4) clinical examples with step-by-step workflows of
      this integration.

PMID- 20033580
TI  - Computer-aided detection of breast carcinoma in standard mammographic projections
      with digital mammography.
AB  - PURPOSE: A retrospective evaluation of the ability of computer-aided detection
      (CAD) ability to identify breast carcinoma in standard mammographic projections.
      MATERIALS AND METHODS: Forty-five biopsy proven lesions in 44 patients imaged
      digitally with CAD applied at examination were reviewed. Forty-four screening
      BIRADS category 1 digital mammography examinations were randomly identified to
      serve as a comparative normal/control population. Data included patient age;
      BIRADS breast density; lesion type, size, and visibility; number, type, and
      location of CAD marks per image; CAD ability to mark lesions; needle core and
      surgical pathologic correlation. RESULTS: The CAD lesion/case sensitivity of 87%
      (n = 39), image sensitivity of 69% (n = 31) for mediolateral oblique view and 78%
      (n = 35) for the craniocaudal view was found. The average false positive rate in
      44 normal screening cases was 2.0 (range 1-8). The 2.0 figure is based on 88
      reported false positive CAD marks in 44 normal screening exams: 98% (n = 44)
      lesions proceeded to excision; initial pathology upgraded at surgical excision
      from in situ to invasive disease in 24% (n = 9) lesions. CONCLUSION: CAD
      demonstrated potential to detect mammographically visible cancers in standard
      projections for all lesion types.

PMID- 20033581
TI  - Three-dimensional appearance of the lips muscles with three-dimensional isotropic
      MRI: in vivo study.
AB  - INTRODUCTION: Our knowledge of facial muscles is based primarily on atlases and
      cadaveric studies. This study describes a non-invasive in vivo method (3D MRI)
      for segmenting and reconstructing facial muscles in a three-dimensional fashion.
      METHODS: Three-dimensional (3D), T1-weighted, 3 Tesla, isotropic MRI was applied
      to a subject. One observer performed semi-automatic segmentation using the Editor
      module from the 3D Slicer software (Harvard Medical School, Boston, MA, USA),
      version 3.2. RESULTS: We were able to successfully outline and three
      dimensionally reconstruct the following facial muscles: pars labialis orbicularis
      oris, m. levatro labii superioris alaeque nasi, m. levator labii superioris, m.
      zygomaticus major and minor, m. depressor anguli oris, m. depressor labii
      inferioris, m. mentalis, m. buccinator, and m. orbicularis oculi. CONCLUSIONS: 3D
      reconstruction of the lip muscles should be taken into consideration in order to
      improve the accuracy and individualization of existing 3D facial soft tissue
      models. More studies are needed to further develop efficient methods for
      segmentation in this field.

PMID- 20033582
TI  - Design of a noise-dependent shrinkage function in wavelet shrinkage of X-ray CT
      image.
AB  - PURPOSE: Many shrinkage functions have been introduced and applied for the
      wavelet shrinkage denoising of computed tomography (CT) images. However, these
      functions have problems in continuity of functions and cause "shrinkage
      artifacts". Therefore, we designed a new and smooth shrinkage function using
      noise distribution. METHODS: The proposed shrinkage function was designed under
      the following four conditions: (1) use of noise distribution, (2) shrunk
      coefficients having all ranges of amplitude, (3) function continuity, and (4)
      property of a function that is controllable by two parameters. The designed
      function was applied to phantom and chest CT images and denoising performance was
      compared with other functions. RESULTS: In the proposed method, edge and pixel
      values were maintained when compared with previous functions, the occurrence of
      shrinkage artifacts was smaller, and high- quality denoised images were obtained.
      CONCLUSIONS: The proposed shrinkage function is effective for low-dose noisy CT
      images when using accurately selected parameters.

PMID- 20033583
TI  - Improving treatment decisions from radiographs: effect of a decision aid.
AB  - PURPOSE: To test whether dental students' accuracy of treatment decision making
      for dentine caries using radiographs improved after using a decision aid (DA).
      METHODS: Dental students (n = 227) assessed the need for treatment for proximal
      surfaces of a test set of radiographs for a scenario patient. These 20 simulated
      bitewings contained 56 proximal test surfaces of which 14 were sound, 19 had
      enamel lesions and 23 had dentine lesions according to the histological "Gold
      standard". The students next used a DA, followed by re-evaluation using the same
      test radiographs. In this test-retest design, paired two-sided T tests were used
      to test for improvement in sensitivity (Se), specificity (Sp) and log diagnostic
      odds ratio (DOR) of treatment decisions for dentine caries. RESULTS: The
      students' initial mean Se, Sp and DOR were 0.66, 0.82, and 12.9 (SD 0.11, 0.10
      and 8.2). After using the decision aid, mean values improved (0.67, 0.83 and
      14.1) (P = 0.83, 0.07 and 0.04). CONCLUSIONS: Using the stand alone DA led to a
      slight improvement in student performance.

PMID- 20033585
TI  - A sub-millimetric, 0.25 mN resolution fully integrated fiber-optic force-sensing
      tool for retinal microsurgery.
AB  - PURPOSE: Retinal microsurgery requires extremely delicate manipulation of retinal
      tissue where tool-to-tissue interaction forces are usually below the threshold of
      human perception. Creating a force-sensing surgical instrument that measures the
      forces directly at the tool tip poses great challenges due to the interactions
      between the tool shaft and the sclerotomy opening. METHODS: We present the design
      and analysis of a force measurement device that senses distal forces interior to
      the sclera using 1-cm long, 160 microm diameter Fiber Bragg Grating (FBG) strain
      sensors embedded in a 0.5 mm diameter tool shaft. Additionally, we provide an
      algorithm developed to cancel the influence of environmental temperature
      fluctuations. RESULTS: The force-sensing prototype measures forces with a
      resolution of 0.25 mN in 2 DOF while being insensitive to temperature.
      CONCLUSION: Sub-millinewton resolution force sensors integrated into
      microsurgical instruments are feasible and have potential applications in both
      robotic and freehand microsurgery.

PMID- 20033584
TI  - The virtual reality tool VirSSPA in planning DIEP microsurgical breast
      reconstruction.
AB  - BACKGROUND: The significant variation in the vascular anatomy of the abdominal
      wall makes preoperative imaging essential when raising a DIEP (deep inferior
      epigastric artery perforator) flap due to the potential for maximizing operative
      success, reducing intraoperative error and minimizing operative complications.
      Variability in perforator anatomy makes DIEP flap surgery a suitable candidate
      for computer and virtual reality bio models. In this context, a study was
      undertaken to determine the feasibility of CTA-guided by VirSSPA application.
      VirSSPA is a virtual reality tool developed in our Hospital for surgical planning
      and training. This application allows surgeons to generate the three-dimensional
      (3D) model of the patient. OBJECTIVE: In this paper, we present a study about
      VirSSPA tool for virtual reality navigation in DIEP flap surgery and compare
      findings with operative measurements. METHODS: We recruited 12 consecutive
      patients planned for an elective DIEP flap for breast reconstruction. Each
      patient underwent preoperative imaging of the anterior abdominal wall vasculature
      with both conventional CTA and VirSSPA 3D reconstruction. Imaging findings were
      compared to operative findings. RESULTS: 3D reconstruction of the abdominal wall
      with VirSSPA demonstrated a significant good correlation with perforator location
      compared to operative findings, showing an average error rate of 0.228 cm (95%
      CI, 0.17-0.30). The Pearson product-moment correlation coefficient was found to
      be 0.99 (p = 0.01), reflecting an almost linear relationship between the two
      distances, intraoperative and the one measured in the 3D reconstruction.
      CONCLUSION: VirSSPA provides additional and potentially more accurate data over
      conventional CTA with regard to the site of the best perforators and its course
      through the muscle for DIEP micro-vascular surgery.

PMID- 20033586
TI  - Vesselness-based 2D-3D registration of the coronary arteries.
AB  - PURPOSE: Robust and accurate automated co-registration of the coronary arteries
      in 3D CTA and 2D X-ray angiography during percutaneous coronary interventions
      (PCI), in order to present a fused visualization. METHODS: A novel vesselness
      based similarity measure was developed, that avoids an explicit segmentation of
      the X-ray image. A stochastic optimizer searches the optimal registration using
      the similarity measure. RESULTS: Both simulated data and clinical data were used
      to investigate the accuracy and capture range of the proposed method. The
      experiments show that the proposed method outperforms the iterative closest point
      method in terms of accuracy (average residual error of 0.42 mm vs. 1.44 mm) and
      capture range (average 71.1 mm/20.3 degrees vs. 14.1 mm/5.2 degrees ).
      CONCLUSION: The proposed method has proven to be accurate and the capture range
      is ample for usage in PCI. Especially the absence of an explicit segmentation of
      the interventionally acquired X-ray images considerably aids the robustness of
      the method.

PMID- 20033587
TI  - Improving education on C-arm operation and radiation protection with a computer
      based training and simulation system.
AB  - PURPOSE: To discuss an approach to improve education in C-arm operation and
      reduction of radiation hazards based on a computer based training and simulation
      system called virtX. METHODS: virtX is equipped with a visualization of scattered
      radiation and means to include patient positioning changes in radiograph
      simulation. virtX was integrated in a course for ORP and evaluated based on
      questionnaires. RESULTS: Response rate was 73 (n = 77), mean age 35.4 (+/-9.2)
      and professional experience 11.2+/- 10.4 years. 91% use a C-arm regularly, 8%
      casually and 1% not. 78% agree that the translation of patient dummy positioning
      changes to simulated X-ray images is sufficiently realistic, 1% disagree (neutral
      17%). 79% state that they acquired new knowledge concerning avoiding unnecessary
      radiation exposure, 10% do not (neutral 11%). CONCLUSIONS: The virtX-approach of
      simulating radiograph generation including patient positioning and scattered
      radiation was evaluated positively concerning its suitability for imparting
      knowledge regarding radiation protection and C-arm operation.

PMID- 20033588
TI  - Haptic guided 3-D deformable image registration.
AB  - PURPOSE: We present a system which supports deformable image registration guided
      by a haptic device. METHODS: The haptic device is tied to a block matching method
      where a set of uniformly distributed control points determine the block
      positions. Each control point constitutes a particle in a mass spring grid which
      limits the space of allowed movements to elastic movements. Control points are
      manipulated by the haptic device, and the negative gradient of the similarity
      metric over the corresponding block is rendered as a force on the haptic device
      guiding the user to a minimum of the optimization landscape. Fast update of
      forces was achieved by exploiting the GPU for computations of the similarity
      metric and for interpolation of the deformation field. RESULTS: We show that
      haptic guided registration facilitates faster and improved registration compared
      to using a purely visual alignment in a user study on synthetic images. We also
      demonstrate feasibility of applying the system on medical images through a
      comparison with an automatic block matching algorithm. A radiologist performing
      registration with the haptic registration system posted faster registration times
      and better registration results than the automatic block matching algorithm when
      using identical grid and block sizes. CONCLUSIONS: Possible applications of the
      system are refinement of registration results from automatic registration methods
      and construction of initial state used in automatic deformable registration
      methods.

PMID- 20033589
TI  - Fast and accurate registration of cranial CT images with A-mode ultrasound.
AB  - PURPOSE: Within the CRANIO project, a navigation module based on preoperative
      computed tomography (CT) data was developed for Computer and Robot Assisted
      Neurosurgery. The approach followed for non-invasive user-interactive
      registration of cranial CT images with the physical operating space consists of
      surface-based registration following pre-registration based on anatomical
      landmarks. Surface-based registration relies on bone surface points digitized
      transcutaneously by means of an optically tracked A-mode ultrasound (US) probe.
      As probe alignment and thus bone surface point digitization may be time
      consuming, we investigated how to obtain high registration accuracy despite
      inaccurate pre-registration and a limited number of digitized bone surface
      points. Furthermore, we aimed at efficient man-machine-interaction during the
      probe alignment process. Finally, we addressed the problem of registration
      plausibility estimation in our approach. METHOD: We modified the Iterative
      Closest Point (ICP) algorithm, presented by Besl and McKay and frequently used
      for surface-based registration, such that it can escape from local minima of the
      cost function to be iteratively minimized. The random-based ICP (R-ICP) we
      developed is less influenced by the quality of the pre-registration as it can
      escape from local minima close to the starting point for iterative optimization
      in the 6D domain of rigid transformations. The R-ICP is also better suited to
      approximate the global minimum as it can escape from local minima in the vicinity
      of the global minimum, too. Furthermore, we developed both CT-less and CT-based
      probe alignment tools along with appropriate man-machine strategies for a more
      time-efficient palpation process. To improve registration reliability, we
      developed a simple plausibility test based on data readily available after
      registration. RESULTS: In a cadaver study, where we evaluated the R-ICP
      algorithm, the probe alignment tools, and the plausibility test, the R-ICP
      algorithm consistently outperformed the ICP algorithm. Almost no influence of the
      pre-registration on the final R-ICP registration accuracy could be observed. The
      probe alignment tools were judged to be useful and allowed for the digitization
      of 18 bone surface points within 2 min on average. The plausibility test was
      helpful to detect poor registration accuracy. CONCLUSION: The R-ICP algorithm can
      provide high registration accuracy despite inaccurate pre-registration and a very
      limited number of data points. R-ICP registration was shown to be practical and
      robust versus the quality of the pre-registration. Time-efficiency of the cranial
      palpation process may be greatly increased and should encourage clinical
      acceptance.

PMID- 20033590
TI  - Statistical model based analysis of bone mineral density of lumbar spine.
AB  - OBJECTIVE: For planning surgical interventions at the spine affected by
      osteoporosis, accurate information about the local bone quality in terms of
      anchorage strength for implants is very important. Based on previous work on
      automated bone quality assessment on the proximal femur with a completely
      automated model-based approach, this paper describes first applications and
      results on the lumbar vertebrae. MATERIALS AND METHODS: As basis for the
      analysis, CT datasets of 17 spinal specimens, with a resolution of 0.7 mm x 0.7
      mm x 0.7 mm have been used. A combined statistical model of 3D shape and
      intensity value distribution was created for these datasets and used to predict
      the measured bone mineral density (BMD). Different regions of interest were
      tested, model parameters with high correlation with BMD were identified. Leave
      one-out tests were performed to evaluate the capability for the BMD-prediction
      using regression models. RESULTS: High correlation values (R = 0.94) between
      measured and predicted BMD were achieved and the high predictive quality of the
      model could be shown. CONCLUSION: Although the results are only valid for an
      insufficient small sample size of specimen data, they show a clear potential for
      clinical application. Therefore, work in the future will focus on clinical
      validation with larger sample size and the inclusion of biomechanical properties
      in addition to BMD.

PMID- 20033591
TI  - Landmarking and segmentation of computed tomographic images of pediatric patients
      with neuroblastoma.
AB  - OBJECTIVES: Segmentation and landmarking of computed tomographic (CT) images of
      pediatric patients are important and useful in computer-aided diagnosis,
      treatment planning, and objective analysis of normal as well as pathological
      regions. Identification and segmentation of organs and tissues in the presence of
      tumors is difficult. Automatic segmentation of the primary tumor mass in
      neuroblastoma could facilitate reproducible and objective analysis of the tumor's
      tissue composition, shape, and volume. However, due to the heterogeneous tissue
      composition of the neuroblastic tumor, ranging from low-attenuation necrosis to
      high-attenuation calcification, segmentation of the tumor mass is a challenging
      problem. In this context, we explore methods for identification and segmentation
      of several abdominal and thoracic landmarks to assist in the segmentation of
      neuroblastic tumors in pediatric CT images. MATERIALS AND METHODS: Methods are
      proposed to identify and segment automatically peripheral artifacts and tissues,
      the rib structure, the vertebral column, the spinal canal, the diaphragm, and the
      pelvic surface. The results of segmentation of the vertebral column, the spinal
      canal, the diaphragm and the pelvic girdle are quantitatively evaluated by
      comparing with the results of independent manual segmentation performed by a
      radiologist. RESULTS AND CONCLUSION: The use of the landmarks and removal of
      several tissues and organs assisted in limiting the scope of the tumor
      segmentation process to the abdomen, and resulted in the reduction of the false
      positive error rates by 22.4%, on the average, over ten CT exams of four
      patients, and improved the result of segmentation of neuroblastic tumors.

PMID- 20033592
TI  - Guided review by frequent itemset mining: additional evidence for plaque
      detection.
AB  - PURPOSE: A guided review process to support manual coronary plaque detection in
      computed tomography coronary angiography (CTCA) data sets is proposed. The method
      learns the spatial plaque distribution patterns by using the frequent itemset
      mining algorithm and uses this knowledge to predict potentially missed plaques
      during detection. MATERIALS AND METHODS: Plaque distribution patterns from 252
      manually labeled patients who underwent CTCA were included. For various cross
      validations a labeling with missing plaques was created from the initial manual
      ground truth labeling. Frequent itemset mining was used to learn the spatial
      plaque distribution patterns in form of association rules from a training set.
      These rules were then applied on a testing set to search for segments in the
      coronary tree showing evidence of containing unlabeled plaques. The segments with
      potentially missed plaques were finally reviewed for the existence of plaques.
      The proposed guided review was compared to a weighted random approach that
      considered only the probability of occurrence for a plaque in a specific segment
      and not its spatial correlation to other plaques. RESULTS: Guided review by
      frequent itemset mining performed significantly better (p < 0.001) than the
      reference weighted random approach in predicting coronary segments with initially
      missed plaques. Up to 47% of the initially removed plaques were refound by only
      reviewing 4.4% of all possible segments. CONCLUSIONS: The spatial distribution
      patterns of atherosclerosis in coronary arteries can be used to predict
      potentially missed plaques by a guided review with frequent itemset mining. It
      shows potential to reduce the intra- and inter-observer variability.

PMID- 20033593
TI  - Customized, rapid-production microstereotactic table for surgical targeting:
      description of concept and in vitro validation.
AB  - PURPOSE: To introduce a novel microstereotactic frame, called the Microtable,
      consisting of a tabletop that mounts on bone-implanted spherical markers. The
      microtable is customized for individual patient anatomy to guide a surgical
      instrument to a specified target. METHODS: Fiducial markers are bone-implanted,
      and CT scanning is performed. A microtable is custom-designed for the location of
      the markers and the desired surgical trajectory and is constructed using a
      computer-numerical-control machine. Validation studies were performed on phantoms
      with geometry similar to that for cochlear implant surgery. Two designs were
      tested with two different types of fiducial markers. RESULTS: Mean targeting
      error of the microtables for the two designs were 0.37 +/- 0.18 and 0.60 +/- 0.21
      mm (n = 5). Construction of each microtable required approximately 6 min.
      CONCLUSIONS: The new frame achieves both high accuracy and rapid fabrication. We
      are currently using the microtable for clinical testing of the concept of
      percutaneous cochlear implant surgery.

PMID- 20033594
TI  - Towards image guided robotic surgery: multi-arm tracking through hybrid
      localization.
AB  - OBJECTIVE: Use of the robotic assisted surgery has been increasing in recent
      years, due both the continuous increase in the number of applications and the
      clinical benefits that surgical robots can provide. Currently robotic assisted
      surgery relies on endoscopic video for navigation, providing only surface
      visualization, thus limiting subsurface vision. To be able to visualize and
      identify subsurface information, techniques in image-guidance can be used. As
      part of designing an image guidance system, all arms of the robot need to be co
      localized in a common coordinate system. METHODS: In order to track multiple arms
      in a common coordinate space, intrinsic and extrinsic tracking methods can be
      used. First, the intrinsic tracking of the daVinci, specifically of the setup
      joints is analyzed. Because of the inadequacy of the setup joints for co
      localization a hybrid tracking method is designed and implemented to mitigate the
      inaccuracy of the setup joints. Different both optical and magnetic tracking
      methods are examined for setup joint localization. RESULTS: The hybrid
      localization method improved the localization accuracy of the setup joints. The
      inter-arm accuracy in hybrid localization was improved to 3.02 mm. This inter-arm
      error value was shown to be further reduced when the arms are co-registered, thus
      reducing common error.

PMID- 20033595
TI  - Liver segmentation by intensity analysis and anatomical information in multi
      slice CT images.
AB  - PURPOSE: Quantitative assessment and essentially segmentation of liver and its
      tumours are of clinical importance in various procedures such as diagnosis,
      treatment planning, and monitoring. Moreover, segmentation of liver is the basis
      of further processing such as visualization, liver resection planning, and liver
      shape analysis. In this paper, we propose an algorithm to estimate an initial
      liver boundary. METHODS: The proposed method consists of four steps as follows:
      first, we compute statistical parameters of liver's intensity range, associated
      with a large cross-section of liver CT image, utilizing expectation maximization
      (EM) algorithm. Second, by automatic extraction of ribs and segmentation of the
      heart, we define a ROI to confine the liver region for the next operations.
      Third, we propose a double thresholding approach to divide the liver intensity
      range into two overlapping ranges. In this case, based on a decision table, we
      label an object as a liver candidate or disregard it from the rest of the
      procedures. Finally, we employ an anatomical based rule to finalize a candidate
      as a liver tissue. In this case, we propose a color-map transformation scheme to
      convert the liver gray images into color images. In this way, we attempt to
      visually differentiate the liver from its surrounding tissues. RESULTS: We have
      evaluated the techniques in the presence of 14 randomly selected local datasets
      as well as all datasets from the MICCAI 2007 Grand Challenge workshop database.
      For the local datasets, the average overlap error and average volume difference
      were of values of 15.3 and 2.8%, respectively. In the case of the MICCAI
      datasets, the above values were estimated as 20.3 and -4.5%, respectively.
      CONCLUSION: The results reveal that the proposed technique is feasible to perform
      consistent initial liver borders. The boundary might be then employed in an
      'Active Contour' algorithm to finalize the liver mask.

PMID- 20033596
TI  - Automated analysis of breast parenchymal patterns in whole breast ultrasound
      images: preliminary experience.
AB  - PURPOSE: A computerized classification scheme to recognize breast parenchymal
      patterns in whole breast ultrasound (US) images was developed. A preliminary
      evaluation of the system performance was performed. METHODS: Breast parenchymal
      patterns were classified into three categories: mottled pattern (MP),
      intermediate pattern (IP), and atrophic pattern (AP). Each classification was
      defined as proposed by an experienced physician. A total of 281 image features
      were extracted from a volume of interest which was automatically segmented.
      Canonical discriminant analysis with stepwise feature selection was employed for
      the classification of the parenchymal patterns. RESULTS: The classification
      scheme accuracy was computed to be 83.3% (10/12 cases) in MP cases, 91.7% (22/24
      cases) in IP cases, 92.9% (13/14 cases) in AP cases, and 90.0% (45/50 cases) in
      all the cases. CONCLUSIONS: The feasibility of an automated ultrasonography
      classifier for parenchymal patterns was demonstrated with promising results in
      whole breast US images.

PMID- 20033597
TI  - Computer-assisted diagnosis of prostate cancer using DCE-MRI data: design,
      implementation and preliminary results.
AB  - OBJECTS: We present computer-assisted diagnosis (CAD) software designed to
      improve prostate cancer detection using perfusion MRI data. METHODS: In addition
      to standard visualization features, this software allows for the 2D and
      multislice 2D contouring of suspicious areas based on a seeded region growing
      algorithm, and area labeling based on zonal anatomy. Tumor volume assessment and
      the semiquantitative analysis of DCE-MRI sequences can both be performed. We
      retrospectively analyzed DCE-MRI examinations of 100 patients and found 121
      lesions showing a suspiciously high intensity with early enhancement in 84 of
      them. Seventy-one patients turned out to be malignant, whereas 50 were benign.
      Based on an analysis of the median wash-in and wash-out values of these foci, we
      designed a standardized 5-level cancer suspicion score (ranging from "probably
      benign" to "highly suspicious"). This comprehensive score provides a scaled
      likelihood of malignancy in the region of interest taking account of its location
      in relation to prostate zonal anatomy. We compared its accuracy with that of
      visual assessments of time-intensity curves performed by specialist and non
      specialist radiologists. RESULTS: Parameters of the scoring algorithm were
      designed to provide the greatest possible sensitivity in our sample population. A
      re-substitution evaluation provided an Se/Sp of 100/45% for peripheral zone
      cancer, and 100/40% for transition zone cancer characterization. When identifying
      malignant areas using time-intensity curves data, this simple algorithm performed
      significantly better (AUC = 0.77) than a non-specialist (AUC = 0.57, P < 0.0001)
      radiologist, and better than a trained (AUC = 0.70) radiologist, although this
      difference was not significant. CONCLUSION: Our new prostate MRI CAD software
      provides a standardized cancer suspicion score for suspicious foci detected in
      DCE-MRI T1-w images. Our results suggest that it may improve radiologists'
      performances in prostate cancer identification, especially when they are not
      specialized in prostate imaging.

PMID- 20033598
TI  - Characterization and classification of tumor lesions using computerized fractal
      based texture analysis and support vector machines in digital mammograms.
AB  - OBJECTIVE: This paper presents a detailed study of fractal-based methods for
      texture characterization of mammographic mass lesions and architectural
      distortion. The purpose of this study is to explore the use of fractal and
      lacunarity analysis for the characterization and classification of both tumor
      lesions and normal breast parenchyma in mammography. MATERIALS AND METHODS: We
      conducted comparative evaluations of five popular fractal dimension estimation
      methods for the characterization of the texture of mass lesions and architectural
      distortion. We applied the concept of lacunarity to the description of the
      spatial distribution of the pixel intensities in mammographic images. These
      methods were tested with a set of 57 breast masses and 60 normal breast
      parenchyma (dataset1), and with another set of 19 architectural distortions and
      41 normal breast parenchyma (dataset2). Support vector machines (SVM) were used
      as a pattern classification method for tumor classification. RESULTS:
      Experimental results showed that the fractal dimension of region of interest
      (ROIs) depicting mass lesions and architectural distortion was statistically
      significantly lower than that of normal breast parenchyma for all five methods.
      Receiver operating characteristic (ROC) analysis showed that fractional Brownian
      motion (FBM) method generated the highest area under ROC curve (A ( z ) = 0.839
      for dataset1, 0.828 for dataset2, respectively) among five methods for both
      datasets. Lacunarity analysis showed that the ROIs depicting mass lesions and
      architectural distortion had higher lacunarities than those of ROIs depicting
      normal breast parenchyma. The combination of FBM fractal dimension and lacunarity
      yielded the highest A ( z ) value (0.903 and 0.875, respectively) than those
      based on single feature alone for both given datasets. The application of the SVM
      improved the performance of the fractal-based features in differentiating tumor
      lesions from normal breast parenchyma by generating higher A ( z ) value.
      CONCLUSION: FBM texture model is the most appropriate model for characterizing
      mammographic images due to self-affinity assumption of the method being a better
      approximation. Lacunarity is an effective counterpart measure of the fractal
      dimension in texture feature extraction in mammographic images. The
      classification results obtained in this work suggest that the SVM is an effective
      method with great potential for classification in mammographic image analysis.

PMID- 20033599
TI  - A pilot study of architectural distortion detection in mammograms based on
      characteristics of line shadows.
AB  - OBJECTIVE: We present herein a novel algorithm for architectural distortion
      detection that utilizes the point convergence index with the likelihood of lines
      (e.g., spiculations) relating to architectural distortion. MATERIALS AND METHODS:
      Validation was performed using 25 computed radiography (CR) mammograms, each of
      which has an architectural distortion with radiating spiculations. The proposed
      method comprises five steps. First, the lines were extracted on mammograms, such
      as spiculations of architectural distortion as well as lines in the mammary
      gland. Second, the likelihood of spiculation for each extracted line was
      calculated. In the third step, point convergence index weighted by this
      likelihood was evaluated at each pixel to enhance distortion only. Fourth, local
      maxima of the index were extracted as candidates for the distortion, then
      classified based on nine features in the last step. RESULTS: Point convergence
      index without the proposed likelihood generated 84.48/image false-positives (FPs)
      on average. Conversely, the proposed index succeeded in decreasing this number to
      12.48/image on average when sensitivity was 100%. After the classification step,
      number of FPs was reduced to 0.80/image with 80.0% sensitivity. CONCLUSION:
      Combination of the likelihood of lines with point convergence index is effective
      in extracting architectural distortion with radiating spiculations.

PMID- 20033600
TI  - Myocardium tracking via matching distributions.
AB  - OBJECTIVE: The goal of this study is to investigate automatic myocardium tracking
      in cardiac Magnetic Resonance (MR) sequences using global distribution matching
      via level-set curve evolution. Rather than relying on the pixelwise information
      as in existing approaches, distribution matching compares intensity
      distributions, and consequently, is well-suited to the myocardium tracking
      problem. MATERIALS AND METHODS: Starting from a manual segmentation of the first
      frame, two curves are evolved in order to recover the endocardium (inner
      myocardium boundary) and the epicardium (outer myocardium boundary) in all the
      frames. For each curve, the evolution equation is sought following the
      maximization of a functional containing two terms: (1) a distribution matching
      term measuring the similarity between the non-parametric intensity distributions
      sampled from inside and outside the curve to the model distributions of the
      corresponding regions estimated from the previous frame; (2) a gradient term for
      smoothing the curve and biasing it toward high gradient of intensity. The
      Bhattacharyya coefficient is used as a similarity measure between distributions.
      The functional maximization is obtained by the Euler-Lagrange ascent equation of
      curve evolution, and efficiently implemented via level-set. The performance of
      the proposed distribution matching was quantitatively evaluated by comparisons
      with independent manual segmentations approved by an experienced cardiologist.
      The method was applied to ten 2D mid-cavity MR sequences corresponding to ten
      different subjects. RESULTS: Although neither shape prior knowledge nor curve
      coupling were used, quantitative evaluation demonstrated that the results were
      consistent with manual segmentations. The proposed method compares well with
      existing methods. The algorithm also yields a satisfying reproducibility.
      CONCLUSION: Distribution matching leads to a myocardium tracking which is more
      flexible and applicable than existing methods because the algorithm uses only the
      current data, i.e., does not require a training, and consequently, the solution
      is not bounded to some shape/intensity prior information learned from of a finite
      training set.

PMID- 20033601
TI  - Localization and registration accuracy in image guided neurosurgery: a clinical
      study.
AB  - PURPOSE: To measure and compare the clinical localization and registration errors
      in image-guided neurosurgery, with the purpose of revising current assumptions.
      MATERIALS AND METHODS: Twelve patients who underwent brain surgeries with a
      navigation system were randomly selected. A neurosurgeon localized and correlated
      the landmarks on preoperative MRI images and on the intraoperative physical
      anatomy with a tracked pointer. In the laboratory, we generated 612 scenarios in
      which one landmark pair was defined as the target and the remaining ones were
      used to compute the registration transformation. Four errors were measured: (1)
      fiducial localization error (FLE); (2) target registration error (TRE); (3)
      fiducial registration error (FRE); (4) Fitzpatrick's target registration error
      estimation (F-TRE). We compared the different errors and computed their
      correlation. RESULTS: The image and physical FLE ranges were 0.5-2.0 and 1.6-3.0
      mm, respectively. The measured TRE, FRE and F-TRE were 4.1 +/- 1.6, 3.9 +/- 1.2,
      and 3.7 +/- 2.2 mm, respectively. Low correlations of 0.19 and 0.37 were observed
      between the FRE and TRE and between the F-TRE and the TRE, respectively. The
      differences of the FRE and F-TRE from the TRE were 1.3 +/- 1.0 mm (max = 5.5 mm)
      and 1.3 +/- 1.2 mm (max = 7.3 mm), respectively. CONCLUSION: Contrary to common
      belief, the FLE presents significant variations. Moreover, both the FRE and the F
      TRE are poor indicators of the TRE in image-to-patient registration.

PMID- 20033602
TI  - Development and validation of a viscoelastic and nonlinear liver model for needle
      insertion.
AB  - OBJECTIVE: The objective of our work is to develop and validate a viscoelastic
      and nonlinear physical liver model for organ model-based needle insertion, in
      which the deformation of an organ is estimated and predicted, and the needle path
      is determined with organ deformation taken into consideration. MATERIALS AND
      METHODS: First, an overview is given of the development of the physical liver
      model. The material properties of the liver considering viscoelasticity and
      nonlinearity are modeled based on the measured data collected from a pig's liver.
      The method to develop the liver model using FEM is also shown. Second, the
      experimental method to validate the model is explained. Both in vitro and in vivo
      experiments that made use of a pig's liver were conducted for comparison with the
      simulation using the model. RESULTS: Results of the in vitro experiment showed
      that the model reproduces nonlinear and viscoelastic response of displacement at
      an internally located point with high accuracy. For a force up to 0.45 N, the
      maximum error is below 1 mm. Results of the in vivo experiment showed that the
      model reproduces the nonlinear increase of load upon the needle during insertion.
      DISCUSSION: Based on these results, the liver model developed and validated in
      this work reproduces the physical response of a liver in both in vitro and in
      vivo situations.

PMID- 20033603
TI  - Setting up MR compatibility of a commercial stereo-localization system for low
      field open MR interventional procedures.
AB  - INTRODUCTION: Surgical and interventional procedures increasingly rely on spatial
      measurement systems. One of the most popular is NDI's Polaris Vicra.
      Unfortunately, this system cannot be used for magnetic resonance imaging (MRI)
      procedures because of the image artifacts that it produces. MATERIALS AND
      METHODS: Here, a simple method for hardware electrical shielding is presented
      which makes the Polaris Vicra MR-compatible for a low-field open-magnet MR
      scanner. The shielding is achieved by placing the cable linking the sensor to the
      USB converter inside a copper braid tube. RESULTS: Tests performed with a variety
      of MR sequences show the absence of image artifacts, image distortion or grey
      level uniformity degradation. In the same way, 3D localization accuracy of the
      spatial measurement system is not modified by the MR environment. A rough safety
      check shows that the system does not pose hazards with normal condition of use.
      CONCLUSION: This minor adaptation makes the system suitable for various
      applications in low field MR environments, such as intraoperative and
      interventional MRI.

PMID- 20033604
TI  - Indexing and retrieving DICOM data in disperse and unstructured archives.
AB  - OBJECTIVE: This paper proposes an indexing and retrieval solution to gather
      information from distributed DICOM documents by allowing searches and access to
      the virtual data repository using a Google-like process. METHODS AND MATERIALS:
      The medical imaging modalities are becoming more powerful and less expensive. The
      result is the proliferation of equipment acquisition by imaging centers,
      including the small ones. With this dispersion of data, it is not easy to take
      advantage of all the information that can be retrieved from these studies.
      Furthermore, many of these small centers do not have large enough requirements to
      justify the acquisition of a traditional PACS. RESULTS: A peer-to-peer PACS
      platform to index and query DICOM files over a set of distributed repositories
      that are logically viewed as a single federated unit. The solution is based on a
      public domain document-indexing engine and extends traditional PACS query and
      retrieval mechanisms. CONCLUSION: This proposal deals well with complex searching
      requirements, from a single desktop environment to distributed scenarios. The
      solution performance and robustness were demonstrated in trials. The
      characteristics of presented PACS platform make it particularly important for
      small institutions, including educational and research groups.

PMID- 20033605
TI  - 3D ultrasound-CT registration of the liver using combined landmark-intensity
      information.
AB  - PURPOSE: An important issue in computer-assisted surgery of the liver is a fast
      and reliable transfer of preoperative resection plans to the intraoperative
      situation. One problem is to match the planning data, derived from preoperative
      CT or MR images, with 3D ultrasound images of the liver, acquired during surgery.
      As the liver deforms significantly in the intraoperative situation non-rigid
      registration is necessary. This is a particularly challenging task because pre-
      and intraoperative image data stem from different modalities and ultrasound
      images are generally very noisy. METHODS: One way to overcome these problems is
      to incorporate prior knowledge into the registration process. We propose a method
      of combining anatomical landmark information with a fast non-parametric intensity
      registration approach. Mathematically, this leads to a constrained optimization
      problem. As distance measure we use the normalized gradient field which allows
      for multimodal image registration. RESULTS: A qualitative and quantitative
      validation on clinical liver data sets of three different patients has been
      performed. We used the distance of dense corresponding points on vessel center
      lines for quantitative validation. The combined landmark and intensity approach
      improves the mean and percentage of point distances above 3 mm compared to rigid
      and thin-plate spline registration based only on landmarks. CONCLUSION: The
      proposed algorithm offers the possibility to incorporate additional a priori
      knowledge-in terms of few landmarks-provided by a human expert into a non-rigid
      registration process.

PMID- 20033606
TI  - Maxillofacial surgery simulation using a mass-spring model derived from continuum
      and the scaled displacement method.
AB  - PURPOSE: Development of a maxillofacial surgery simulation software capable of
      predicting a patient's appearance after surgery. METHODS: We have derived a new
      mass-spring model (MSM) equivalent to a linear finite element (FE) model for
      cubic elements. In addition, we propose the scaled displacement method as a new
      method to perform the simulation more realistically. RESULTS: The average error
      of eight soft tissue landmarks measured between 0.37 and 2.01 mm except from a
      landmark that had an error of 4.44 mm; values close to those obtained with the
      linear FE method. On the other hand, the scaled displacement method allows
      avoiding punctual stress concentration and bending effects making a much more
      realistic simulation in the region of the bone cut. CONCLUSIONS: Good results
      have been achieved with our two proposed methods. In addition, the simple way in
      which MSM can be parallelized makes it an interesting alternative to FE method.

PMID- 20033607
TI  - Preoperative workflow for lymph nodes staging.
AB  - PURPOSE: Accurate staging of lymph nodes relies mainly on surgical exploration
      and manual palpation. We present a new non-invasive diagnostic approach:
      simulated palpation through virtual laparoscopic instruments. METHODS: We set up
      a diagnostic process to extract lymph nodes shape and position from CTs and to
      analyze the trend of pixels intensities to determine tissue properties in order
      to feedback the force information. RESULTS: We have integrated the model,
      obtained from both the morphological information and stiffness values, in our
      laparoscopy simulator and surgeons can virtually palpate, with a haptic device,
      the lymph nodes. We evaluated the workflow extracting lymph nodes from a case
      study: the feedback provided through the simulator greatly helps the surgeon in
      the correct staging. CONCLUSIONS: Results show the feasibility of the approach
      and in the future we will clinically evaluate this new diagnostic methodology. We
      are studying the possibility to integrate CTs with other imaging systems to
      increase the accuracy.

PMID- 20033608
TI  - Towards navigation on the heart surface during coronary arterty bypass grafting.
AB  - OBJECT: Coronary artery bypass grafting (CABG) is the standard treatment for
      advanced coronary artery diseases. In a preoperative MSCT, both wall plaque
      formations and resulting optimal anastomotic site are visible to the surgeon.
      During surgery, the identification of this position on the surface of the heart
      is of utmost importance for an effective revascularisation procedure. To assist
      the surgeon in this matter, a surgical navigation system for the open heart is
      desirable. This work focusses on an appropriate method for registration of a
      patient-specific map of the coronaries extracted from preoperative MSCT data with
      optical tracking data recorded intraoperatively at the ischaemic heart. METHODS:
      The proposed registration process is based on mutually shared anatomical point
      landmarks and vessel paths on the heart surface utilised in an enhanced weighted
      ICP algorithm. Bypass grafting predominantly takes place at the ischaemic heart
      which is significantly distorted compared to its preoperative shape. To account
      for that, the method includes corrections for the effects of muscle relaxation
      and torsion of the ischaemic heart. RESULTS: The registration process was tested
      retrospectively on real patient data recorded at the ischaemic heart during
      bypass grafting. After registration, the vessel paths and point landmarks
      recorded intraoperatively by the surgeon showed good accordance with the
      preoperative map of the coronaries. CONCLUSION: The registration method presented
      here is capable of matching the relevant parts of a preoperatively extracted map
      of the coronaries with intraoperatively recorded optical tracking data. Thus, it
      can be used as a basis for a surgical navigation system intended to assist the
      surgeon in the localisation of the optimal anastomotic site during CABG.

PMID- 20033609
TI  - Inside the beating heart: an in vivo feasibility study on fusing pre- and intra
      operative imaging for minimally invasive therapy.
AB  - OBJECTIVE: An interventional system for minimally invasive cardiac surgery was
      developed for therapy delivery inside the beating heart, in absence of direct
      vision. METHOD: A system was developed to provide a virtual reality (VR)
      environment that integrates pre-operative imaging, real-time intra-operative
      guidance using 2D trans-esophageal ultrasound, and models of the surgical tools
      tracked using a magnetic tracking system. Detailed 3D dynamic cardiac models were
      synthesized from high-resolution pre-operative MR data and registered within the
      intra-operative imaging environment. The feature-based registration technique was
      employed to fuse pre- and intra-operative data during in vivo intracardiac
      procedures on porcine subjects. RESULTS: This method was found to be suitable for
      in vivo applications as it relies on easily identifiable landmarks, and hence, it
      ensures satisfactory alignment of pre- and intra-operative anatomy in the region
      of interest (4.8 mm RMS alignment accuracy) within the VR environment. Our
      initial experience in translating this work to guide intracardiac interventions,
      such as mitral valve implantation and atrial septal defect repair demonstrated
      feasibility of the methods. CONCLUSION: Surgical guidance in the absence of
      direct vision and with no exposure to ionizing radiation was achieved, so our
      virtual environment constitutes a feasible candidate for performing various off
      pump intracardiac interventions.

PMID- 20033611
TI  - VirSSPA- a virtual reality tool for surgical planning workflow.
AB  - OBJECTIVE: A virtual reality tool, called VirSSPA, was developed to optimize the
      planning of surgical processes. METHODS: Segmentation algorithms for Computed
      Tomography (CT) images: a region growing procedure was used for soft tissues and
      a thresholding algorithm was implemented to segment bones. The algorithms operate
      semiautomati- cally since they only need seed selection with the mouse on each
      tissue segmented by the user. The novelty of the paper is the adaptation of an
      enhancement method based on histogram thresholding applied to CT images for
      surgical planning, which simplifies subsequent segmentation. A substantial
      improvement of the virtual reality tool VirSSPA was obtained with these
      algorithms. RESULTS: VirSSPA was used to optimize surgical planning, to decrease
      the time spent on surgical planning and to improve operative results. The success
      rate increases due to surgeons being able to see the exact extent of the
      patient's ailment. This tool can decrease operating room time, thus resulting in
      reduced costs. CONCLUSION: Virtual simulation was effective for optimizing
      surgical planning, which could, consequently, result in improved outcomes with
      reduced costs.

PMID- 20033610
TI  - The effect of CyberDome, a novel 3-dimensional dome-shaped display system, on
      laparoscopic procedures.
AB  - BACKGROUND: Laparoscopic surgeons require extended experience of cases to
      overcome the lack of depth perception on a two-dimensional (2D) display. Although
      a three-dimensional (3D) display was reported to be useful over two decades ago,
      3D systems have not been widely used. Recently, we developed a novel 3D dome
      shaped display (3DD) system, CyberDome. STUDY DESIGN: In the present study, a
      total of 23 students volunteered. We evaluated the effects of the 3DD system on
      depth perception and laparoscopic procedures in comparison with the 2D, a
      conventional 3D (3DP) or the 2D high definition (HD) systems using seven tasks.
      RESULTS: The 3DD system significantly improved depth perception and laparoscopic
      performance compared with the 2D system in six new tasks. We further found that
      the 3DD system shortened the execution time and reduced the number of errors
      during suturing and knot tying. The 3DD system also provided more depth
      perception than the 3DP and 2D HD systems. CONCLUSIONS: The novel 3DD system is a
      promising tool for providing depth perception with high resolution to
      laparoscopic surgeons.

PMID- 20033612
TI  - Automatic registration using implicit shape representations: applications in
      intraoperative 3D rotational angiography to preoperative CTA registration.
AB  - PURPOSE: A solution for automatic registration of 3D Rotational Angiography (XA)
      to CT/MR of the liver. Targeted for use in treatment planning of liver
      interventions. METHODS: A shape-based approach to registration is proposed that
      does not require specification of landmarks nor is it prone to local minima like
      purely intensity-based registration methods. Through the use of vessel
      characteristics, accurate registration is possible even in the presence of
      deformations induced by catheters and respiratory motion. RESULTS: Registration
      was performed on eight pairs of multiphase CT angiography and 3D rotational
      digital angiography datasets. Quantitative validation of the registration
      accuracy using vessel landmarks was performed on these datasets. The validation
      study showed that the method has a registration error of 9.41 +/- 4.13 mm. In
      addition, the computation time is well below 60 s making it attractive for
      clinical application. CONCLUSION: A new method for fully automatic 3DXA to CT/MR
      image registration was developed and found to be efficient and accurate using
      clinically realistic datasets.

PMID- 20033613
TI  - Evaluation of bivariate correlation ratio similarity metric for rigid
      registration of US/MR images of the liver.
AB  - OBJECTIVE: Radio frequency ablation (RFA) can be used to treat liver cancer
      minimally invasively by depositing energy from the RF probe placed in the center
      of the tumor. The procedure relies on pre-operative imaging (typically MRI or CT)
      for the interventional planning and ultrasound (US) for intra-operative guidance
      during needle insertion. Visual presentation of co-registered pre- and intra
      operative images would help to improve the navigation during the needle
      positioning phase. METHODS: In the present study, we compared six registration
      methods using different similarity metrics: two versions of the correlation
      ratio, bivariate correlation ratio, and conventional normalized mutual
      information and correlation coefficient. The accuracy, robustness and speed were
      assessed by computing rigid registrations between eight pairs of the MR and
      freehand 3D US datasets. RESULTS: The correlation ratio computed on the MR
      gradient-norm and US images outperformed other similarity metrics in terms of
      robustness (40-82%) and demonstrated average accuracy (0.32 degrees , 0.69 mm)
      which is clinically acceptable for the RFA of liver cancer. CONCLUSIONS: We
      observed that the performance of all similarity metrics is largely dependent on
      the quality of the US images, sufficient field of view of the reconstructed 3D US
      and absence of motion artifacts.

PMID- 20033614
TI  - Robot-assisted primary cementless total hip arthroplasty using surface
      registration techniques: a short-term clinical report.
AB  - PURPOSE: The purpose of this study was to compare non-fiducial based surface
      registration technique (DigiMatch) with the conventional locator pin-based
      registration technique in performing cementless total hip arthroplasty (THA)
      using ROBODOC system. METHODS: Eighty-one THA were performed using pin-based
      technique and forty-three were performed using the DigiMatch technique. The
      average follow-up term was 38 months. RESULTS: Postoperatively, the Japanese
      Orthopedic Association hip scores were significantly better in the DigiMatch
      group than in pin-based group. The accuracy of postoperative stem alignment of
      the DigiMatch technique was comparable with that of pin-based method.
      CONCLUSIONS: No need for prior pin implantation surgery and no concern for pin
      related knee pain were the advantages of DigiMatch technique. Short-term follow
      up clinical results showed that DigiMatch ROBODOC THA was safe and effective.

PMID- 20033615
TI  - Development of a clinically applicable tool for bone density assessment.
AB  - OBJECTIVES: To assess the accuracy and reliability of new software for
      radiodensitometric evaluations. METHODS: A densitometric tool developed by
      MevisLab was used in conjunction with intraoral radiographs of the premolar
      region in both in vivo and laboratory settings. An aluminum step wedge was
      utilized for comparison of grey values. After computer-aided segmentation, the
      interproximal bone between the premolars was assessed in order to determine the
      mean grey value intensity of this region and convert it to a thickness in
      aluminum. Evaluation of the tool was determined using bone mineral density (BMD)
      values derived from decalcified human bone specimens as a reference standard. In
      vivo BMD data was collected from 35 patients as determined with dual X-ray
      absorptiometry (DXA). The intra and interobserver reliability of this method was
      assessed by Bland and Altman Plots to determine the precision of this tool.
      RESULTS: In the laboratory study, the threshold value for detection of bone loss
      was 6.5%. The densitometric data (mm Al eq.) was highly correlated with the jaw
      bone BMD, as determined using dual X-ray absorptiometry (r = 0.96). For the in
      vivo study, the correlations between the mm Al equivalent of the average upper
      and lower jaw with the lumbar spine BMD, total hip BMD and femoral neck BMD were
      0.489, 0.537 and 0.467, respectively (P < 0.05). For the intraobserver
      reliability, a Bland and Altman plot showed that the mean difference +/- 1.96 SD
      were within +/-0.15 mm Al eq. with the mean difference value small than 0.003 mm
      Al eq. For the interobserver reliability, the mean difference +/-1.96 SD were
      within +/-0.11 mm Al eq. with the mean difference of 0.008 mm Al eq. CONCLUSIONS:
      A densitometric software tool has been developed, that is reliable for bone
      density assessment. It now requires further investigation to evaluate its
      accuracy and clinical applicability in large scale studies.

PMID- 20033616
TI  - Prevalence of carotid and pulp calcifications: a correlation using digital
      panoramic radiographs.
AB  - OBJECTIVE: To compare the prevalence of pulp calcification with that of carotid
      calcification using digital panoramic dental radiographs. STUDY DESIGN: Digital
      panoramic radiographs of patients at a dental oncology clinic were included if
      (1) the carotid artery bifurcation region was visible bilaterally and (2) the
      patient had non-restored or minimally restored molars and/or canines. An
      endodontist evaluated the images for pulpal calcifications in the selected teeth.
      An oral and maxillofacial radiologist independently evaluated the same images for
      calcifications in the carotid bifurcation region. Odds-ratio and Pearson chi(2)
      were used for data analysis. Presence of pulpal calcification was also evaluated
      as a screening test for the presence of carotid calcification. RESULTS: A total
      of 247 panoramic radiographs were evaluated. 32% (n = 80) had pulpal
      calcifications and 25% (n = 61) had carotid calcifications with 12% (n = 29)
      having both carotid and pulp calcifications. A significantly higher prevalence of
      both pulp and carotid calcification was found in subjects older than age 60 years
      compared to younger age groups. Accuracy of pulpal calcification in screening for
      carotid calcification was 66.4%. CONCLUSIONS: Both pulp and carotid
      calcifications were more prevalent in older individuals. The presence of pulp
      calcification was not a strong predictor for the presence of carotid
      calcification.

PMID- 20033617
TI  - Generation of three-dimensional prototype models based on cone beam computed
      tomography.
AB  - PURPOSE: The purpose of this study was to generate three-dimensional models based
      on digital volumetric data that can be used in basic and advanced education.
      METHODS: Four sets of digital volumetric data were established by cone beam
      computed tomography (CBCT) (Accuitomo, J. Morita, Kyoto, Japan). Datasets were
      exported as Dicom formats and imported into Mimics and Magic software programs to
      separate the different tissues such as nerve, tooth and bone. These data were
      transferred to a Polyjet 3D Printing machine (Eden 330, Object, Israel) to
      generate the models. RESULTS: Three-dimensional prototype models of certain
      limited anatomical structures as acquired volumetrically were fabricated.
      CONCLUSIONS: Generating three-dimensional models based on CBCT datasets is
      possible. Automated routine fabrication of these models, with the given
      infrastructure, is too time-consuming and therefore too expensive.

PMID- 20033618
TI  - Combining a deformable model and a probabilistic framework for an automatic 3D
      segmentation of prostate on MRI.
AB  - PURPOSE: Accurate localization and contouring of prostate are crucial issues in
      prostate cancer diagnosis and/or therapies. Although several semi-automatic and
      automatic segmentation methods have been proposed, manual expert correction
      remains necessary. We introduce a new method for automatic 3D segmentation of the
      prostate gland from magnetic resonance imaging (MRI) scans. METHODS: A
      statistical shape model was used as an a priori knowledge, and gray levels
      distribution was modeled by fitting histogram modes with a Gaussian mixture.
      Markov fields were used to introduce contextual information regarding voxels'
      neighborhoods. Final labeling optimization is based on Bayesian a posteriori
      classification, estimated with the iterative conditional mode algorithm. RESULTS:
      We compared the accuracy of this method, free from any manual correction, with
      contours outlined by an expert radiologist. In 12 cases, including prostates with
      cancer and benign prostatic hypertrophy, the mean Hausdorff distance and overlap
      ratio were 9.94 mm and 0.83, respectively. CONCLUSION: This new automatic
      prostate MRI segmentation method produces satisfactory results, even at
      prostate's base and apex. The method is computationally feasible and efficient.

PMID- 20033619
TI  - Vascular tree reconstruction with discrete tomography: intensity based camera
      correction for 3D reconstruction.
AB  - PURPOSE: This paper is concerned with the reconstruction of vascular trees from
      few projections using discrete tomography. However, its computational cost is
      high and it lacks robustness when the data are inconsistent. We improve
      robustness by incorporating an intensity-based camera-correction method. The
      proposed approach is also capable of handling small motion artifacts by modeling
      them as repositionings of a virtual X-ray camera. We also present a parallel
      implementation which substantially reduces reconstruction time. METHODS: We
      propose a data-driven reduction of positional inconsistencies by minimizing the
      reconstruction residual to increase the robustness. Inspired by motion compen
      sation algorithms in SPECT imaging, we combine an intensity-based 2D/3D
      registration method with itera-tive reconstruction methods. Our objective is the
      robust vascular-tree reconstruction from positionally inconsistent data. The
      speed of the reconstruction is substantially increased by a volume-splitting
      scheme that allows parallel processing. RESULTS: Vascular trees in the liver can
      be accurately reconstructed from few positionally inconsistent projections using
      digitally reconstructed radiographs. We have tested the proposed method on
      synthetic projection data and on objects imaged with a new robotized C-arm. We
      measured a decrease in the average reconstruction residual of about 13% for real
      data compared to projection data without preprocessing. Over 4,600 reconstruction
      experiments were conducted to evaluate the speed-up obtained when employing the
      volume-splitting scheme. Reconstruction time decreased linearly with increased
      number of processor-cores, both for real and synthetic data. CONCLUSIONS: The
      proposed method reduces inconsistencies caused by positioning errors and small
      motion artifacts. No prior segmentation or detection of correspondences between
      projections is necessary, because all algorithms are intensity-based. As a
      result, the proposed method allows for robust, high-quality reconstructions,
      while reducing radiation dose substantially.

PMID- 20033620
TI  - Comparing calibration approaches for 3D ultrasound probes.
AB  - OBJECTIVE: By adding a tracking sensor to a 3D ultrasound (US) probe and thus
      locating the probe in space, new applications within the fields of image guided
      surgery and radiation therapy are possible. To locate the US volume in space, a
      calibration is necessary to determine the mathematical transformation for mapping
      points from the tracking coordinate system to the US image coordinate system. We
      present a comprehensive comparison of two different approaches to perform this
      calibration for 3D US. METHODS: For both approaches a phantom is scanned and
      located in the images by means of segmentation and registration techniques.
      Calibration is then performed by either relating the tracked phantom's (TP)
      spatial location to the calibration scans, or by solely correlating scans taken
      from multiple perspectives when using hand-eye calibration methods (HE).
      Depending on which approach is utilized, a minimum of one or three images,
      respectively, need to be acquired for the calibration process. RESULTS: We
      evaluated both approaches for calibration and reconstruction precision. Regarding
      the latter, the performed tests led to mean target localization errors of 3.5 mm
      (HE) and 3.3 mm (TP) for real data, and of 1.4 mm (HE) and 0.9 mm (TP) for
      simulated data. CONCLUSION: Our results indicate that taking additional scans
      leads to a significant improvement in the calibration. Furthermore, the obtained
      calibration and reconstruction precisions suggest the use of a TP.

PMID- 20033621
TI  - Are electronic medical records helpful for care coordination? Experiences of
      physician practices.
AB  - BACKGROUND: Policies promoting widespread adoption of electronic medical records
      (EMRs) are premised on the hope that they can improve the coordination of care.
      Yet little is known about whether and how physician practices use current EMRs to
      facilitate coordination. OBJECTIVES: We examine whether and how practices use
      commercial EMRs to support coordination tasks and identify work-around practices
      have created to address new coordination challenges. DESIGN, SETTING: Semi
      structured telephone interviews in 12 randomly selected communities.
      PARTICIPANTS: Sixty respondents, including 52 physicians or staff from 26
      practices with commercial ambulatory care EMRs in place for at least 2 years,
      chief medical officers at four EMR vendors, and four national thought leaders.
      RESULTS: Six major themes emerged: (1) EMRs facilitate within-office care
      coordination, chiefly by providing access to data during patient encounters and
      through electronic messaging; (2) EMRs are less able to support coordination
      between clinicians and settings, in part due to their design and a lack of
      standardization of key data elements required for information exchange; (3)
      managing information overflow from EMRs is a challenge for clinicians; (4)
      clinicians believe current EMRs cannot adequately capture the medical decision
      making process and future care plans to support coordination; (5) realizing EMRs'
      potential for facilitating coordination requires evolution of practice
      operational processes; (6) current fee-for-service reimbursement encourages EMR
      use for documentation of billable events (office visits, procedures) and not of
      care coordination (which is not a billable activity). CONCLUSIONS: There is a gap
      between policy-makers' expectation of, and clinical practitioners' experience
      with, current electronic medical records' ability to support coordination of
      care. Policymakers could expand current health information technology policies to
      support assessment of how well the technology facilitates tasks necessary for
      coordination. By reforming payment policy to include care coordination,
      policymakers could encourage the evolution of EMR technology to include
      capabilities that support coordination, for example, allowing for inter-practice
      data exchange and multi-provider clinical decision support.

PMID- 20033622
TI  - The effects of guided care on the perceived quality of health care for multi
      morbid older persons: 18-month outcomes from a cluster-randomized controlled
      trial.
AB  - BACKGROUND: The quality of health care for older Americans with chronic
      conditions is suboptimal. OBJECTIVE: To evaluate the effects of "Guided Care" on
      patient-reported quality of chronic illness care. DESIGN: Cluster-randomized
      controlled trial of Guided Care in 14 primary care teams. PARTICIPANTS: Older
      patients of these teams were eligible to participate if, based on analysis of
      their recent insurance claims, they were at risk for incurring high health-care
      costs during the coming year. Small teams of physicians and their at-risk older
      patients were randomized to receive either Guided Care (GC) or usual care (UC).
      INTERVENTION: "Guided Care" is designed to enhance the quality of health care by
      integrating a registered nurse, trained in chronic care, into a primary care
      practice to work with 2-5 physicians in providing comprehensive chronic care to
      50-60 multi-morbid older patients. MEASUREMENTS: Eighteen months after baseline,
      interviewers blinded to group assignment administered the Patient Assessment of
      Chronic Illness Care (PACIC) survey by telephone. Logistic and linear regression
      was used to evaluate the effect of the intervention on patient-reported quality
      of chronic illness care. RESULTS: Of the 13,534 older patients screened, 2,391
      (17.7%) were eligible to participate in the study, of which 904 (37.8%) gave
      informed consent and were cluster-randomized. After 18 months, 95.3% and 92.2% of
      the GC and UC recipients who remained alive and eligible completed interviews.
      Compared to UC recipients, GC recipients had twice greater odds of rating their
      chronic care highly (aOR = 2.13, 95% CI = 1.30-3.50, p = 0.003). CONCLUSION:
      Guided Care improves self-reported quality of chronic health care for multi
      morbid older persons.

PMID- 20033623
TI  - Consumer awareness and strategies among families with high-deductible health
      plans.
AB  - OBJECTIVE: High-deductible health plans (HDHPs) are a new and controversial
      approach to increasing the share of health care costs paid by patients. Our study
      had the following aims: (1) to describe the experiences of families with HDHPs
      who had incurred high out-of-pocket costs and (2) to identify areas where
      clinicians could support more effective health care decisions by such families.
      METHODS: We conducted four focus groups with adults whose families had HDHPs in a
      New England-based health plan and had experienced high or unexpected out-of
      pocket health care costs during the past 12 months. Transcripts of audio
      recordings were independently coded by three investigators using modified
      grounded theory techniques. RESULTS: The 21 focus group participants had a good
      general understanding of how their HDHP worked, but reported confusion about
      specific processes due to the plans' complexity. They described heightened
      awareness of health care costs, and identified important barriers to their
      ability to control costs. These included needing to seek care for urgent problems
      without having the time to assess potential costs; having mistaken expectations
      about what services the HDHP covered; and being reluctant to discuss costs with
      doctors. They attempted to control costs by delaying or avoiding visits to
      doctors, but felt they had little control over costs once a clinical encounter
      had begun. CONCLUSIONS: Patients with HDHPs reported heightened sensitivity to
      health care costs, and described important barriers to their ability to make
      effective choices. Helping such patients make optimal decisions will likely
      require systems-level changes that involve clinicians and health insurers.

PMID- 20033624
TI  - "We'll do this together": the role of the first person plural in fostering
      partnership in patient-physician relationships.
AB  - BACKGROUND: Partnership is integral to therapeutic relationships, yet few studies
      have examined partnership-fostering communication behaviors in the clinic
      setting. We conducted this study to better understand how statements in which
      physicians use the first person plural might foster partnership between patient
      and provider. METHODS: We audio-recorded encounters between 45 HIV providers and
      418 patients in the Enhancing Communication and HIV Outcomes (ECHO) Study. We
      used the Roter Interaction Analysis System (RIAS) to code for statements made by
      the physician that used the first person plural to refer to themselves and their
      patient. Using multiple logistic regression, we examined the associations between
      the occurrence of one or more first person plural statements with patient ratings
      of provider communication. To better understand the meaning of first person
      plural statements, we conducted a qualitative analysis. MAIN RESULTS: Providers
      were mostly white (69%) and Asian (24%); 57% were female. Patients were black
      (60%), white (25%), and Hispanic (15%); 33% were female. One or more first person
      plural statements occurred in 92/418 (22%) of encounters. In adjusted analyses,
      encounters with first person plural statements were associated with younger
      patient age (OR 0.97, 95% CI 0.94-0.99), higher patient depression scores
      (highest tertile compared to lowest tertile: OR 1.89, 95% CI 1.01-3.51), the
      patient not being on anti-retroviral therapy (OR 0.53, 95% CI 0.29-0.93), and
      older provider age (OR 1.05, 95% CI 1.00-1.09). After adjustment, patients were
      less likely to highly rate their provider's communication style if first person
      plural statements were used (AOR 0.57, 95% CI 0.33-0.96). There were 167 first
      person plural statements made by physicians in the 418 encounters. Qualitative
      analysis revealed that many first person plural features had at least one
      negative feature such as being overtly persuasive ("That's going to be our
      goal"), indirect ("What can we do to improve your diet?"), or ambiguous ("Let's
      see what we can do"), although there were also positive statements that involved
      patients in the health-care process, contributed to a mutual understanding, and
      addressed the patients' goals. CONCLUSIONS: Contrary to our hypotheses, use of
      first person plural was not associated with higher ratings of provider
      communication, probably because some of these statements were overtly persuasive,
      indirect, or ambiguous. Physicians should become aware of benefits and pitfalls
      of using the first person plural with patients. Further research is needed to
      determine the most effective methods through which providers can build alliances
      with patients.

PMID- 20033625
TI  - Probing cell structure responses through a shear and stretching mechanical
      stimulation technique.
AB  - Cells are complex, dynamic systems that respond to various in vivo stimuli
      including chemical, mechanical, and scaffolding alterations. The influence of
      mechanics on cells is especially important in physiological areas that dictate
      what modes of mechanics exist. Complex, multivariate physiological responses can
      result from multi-factorial, multi-mode mechanics, including tension,
      compression, or shear stresses. In this study, we present a novel device based on
      elastomeric materials that allowed us to stimulate NIH 3T3 fibroblasts through
      uniaxial strip stretching or shear fluid flow. Cell shape and structural response
      was observed using conventional approaches such as fluorescent microscopy. Cell
      orientation and actin cytoskeleton alignment along the direction of applied force
      were observed to occur after an initial 3 h time period for shear fluid flow and
      static uniaxial strip stretching experiments although these two directions of
      alignment were oriented orthogonal relative to each other. This response was then
      followed by an increasingly pronounced cell and actin cytoskeleton alignment
      parallel to the direction of force after 6, 12, and 24 h, with 85% of the cells
      aligned along the direction of force after 24 h. These results indicate that our
      novel device could be implemented to study the effects of multiple modes of
      mechanical stimulation on living cells while probing their structural response
      especially with respect to competing directions of alignment and orientation
      under these different modes of mechanical stimulation. We believe that this will
      be important in a diversity of fields including cell mechanotransduction, cell
      material interactions, biophysics, and tissue engineering.

PMID- 20033626
TI  - Langmuir films from human placental membranes: preparation, rheology, transfer to
      alkylated glasses, and sigmoidal kinetics of alkaline phosphatase in the
      resultant Langmuir-Blodgett film.
AB  - In the present study, we studied the activity of human placental alkaline
      phosphatase (PLAP) constraint in a planar surface in controlled molecular packing
      conditions. For the first time, Langmuir films (LFs) were prepared by the
      spreading of purified placental membranes (PPM) on the air-water interface and
      their stability and rheological properties were studied. LFs exhibited a collapse
      pressure pi(C) = 48 mN/m, hysteresis during the compression-decompression cycle
      (C-D), indicating a plastic deformation, and a compressibility modulus (K)
      compatible with liquid-expanded phases. A phase transition point appeared at
      pi(T) = 28 mN/m and, following successive C-D, it moved toward lower surface
      areas and higher K, suggesting the lost of some non-PLAP proteins as components
      of vesicles that might protrude from the monolayer (confirmed by combining
      lipid/protein molar ratio analysis, PAGE-SDS and V(max)). LFs were transferred at
      35 mN/m to alkylated glasses to obtain Langmuir-Blodgett films (LB(35)) the
      stability of which was confirmed by AFM. The kinetics of p-nitrophenyl phosphate
      (pNPP) hydrolysis at 37 degrees C catalyzed by PPM was Michaelian and exhibited
      the thermostability at 60 degrees C typical of PLAP. In LB(35), PLAP exhibited a
      sigmoidal kinetics which resembled the behavior of the partially metalated enzyme
      but might become from a cross-talk between protein and membrane structures.

PMID- 20033627
TI  - Homocysteine potentiates seizures and cell loss induced by pilocarpine treatment.
AB  - Patients affected by recurrent seizures frequently present increased homocysteine
      plasma levels in consequence of treatment with antiepileptic drugs. Homocysteine
      is proconvulsant and can affect the response to antiepileptic drugs. In addition,
      high homocysteine plasma levels represent a risk factor for cardiovascular and
      neurodegenerative diseases. To better define the role of increased homocysteine
      in epilepsy, we analyzed the effects of homocysteine pretreatment in the
      pilocarpine model of status epilepticus (SE), which is used to mimic temporal
      lobe epilepsy (TLE) in rodents. Precisely, we investigated whether a moderate
      hyperhomocysteinemia, unable to cause seizures, could sensitize rats to
      pilocarpine and cooperate in inducing brain lesions. We found that a subthreshold
      dose of pilocarpine (200 mg/kg) is sufficient to induce SE in the majority
      (approximately 90%) of rats pretreated with homocysteine for 2 weeks, whereas
      only 40% of saline-treated controls developed SE following the same pilocarpine
      dose. Furthermore, homocysteine pretreatment led to a significant increase in
      neuronal cell loss evaluated by counting toluidine blue-stained or Fluoro-Jade
      positive cells in hippocampal and parahippocampal regions. Pilocarpine augmented
      amyloid beta expression in both animal groups. However, pretreatment with
      homocysteine favored the intraneuronal fibrillar conformation of amyloid beta,
      thus promoting neurodegeneration. These findings indicate that increased
      homocysteine levels enhance seizure activity and neurodegeneration in pilocarpine
      treated rats and suggest that similar detrimental effects may occur in patients
      affected by TLE.

PMID- 20033628
TI  - Long-term results of pirarubicin versus doxorubicin in combination chemotherapy
      for aggressive non-Hodgkin's lymphoma: single center, 15-year experience.
AB  - Pirarubicin is an analog of doxorubicin. Few studies have compared the long-term
      outcomes of patients receiving pirarubicin-based THP-COP and doxorubicin-based
      CHOP in the treatment of non-Hodgkin's lymphoma (NHL). We retrospectively
      compared the efficacy and safety of these two regimens in 459 previously
      untreated aggressive NHL patients admitted to Sun Yat-Sen University Cancer
      Center from 1987 to 2003. For initial treatment, 205 patients received the THP
      COP regimen, and 254 patients received the CHOP regimen. The patients'
      characteristics were well balanced. The groups did not differ in the complete
      remission rate (THP-COP, 57.1% vs. CHOP, 57.0%; P = 0.998) or response rate (THP
      COP, 82.9% vs. CHOP, 81.5%; P = 0.691). At a median follow-up of 95.7 months, the
      8-year survival rates were also similar (overall survival: THP-COP, 55.8% vs.
      CHOP, 56.7%; progression-free survival: THP-COP, 47.3% vs. CHOP, 43.5%; lymphoma
      specific survival: THP-COP, 51.2% vs. CHOP, 48.5%). The THP-COP group had fewer
      cases of alopecia (P < 0.001) and gastrointestinal toxicities (P = 0.015). A
      tendency toward decreased arrhythmia (P = 0.075), especially in elderly patients
      (P = 0.030), was found. In combination chemotherapy for aggressive NHL,
      pirarubicin has comparable efficacy to doxorubicin and has a lower incidence of
      alopecia, gastrointestinal toxicities, and arrhythmia. Further studies are
      warranted to confirm these results.

PMID- 20033629
TI  - Low goal ownership predicts drop-out from a weight intervention study in
      overweight patients with type 2 diabetes.
AB  - BACKGROUND: Drop-out is a major problem in weight loss studies. Although previous
      attrition research has examined some predictors of drop-out, theoretically
      grounded research on psychological predictors of drop-out from weight
      interventions has been lacking. PURPOSE: To examine psychological predictors of
      drop-out from a weight reduction study in diabetes type 2 patients. METHOD: A
      clinical trial was conducted with 101 overweight/obese (body mass index >27)
      diabetes type 2 patients. Patients were randomly assigned to a self-regulation
      intervention, an active control group, and a passive control group.
      Psychological, somatic, socio-demographic, and lifestyle variables were examined
      as predictors of drop-out from baseline to 6 months follow-up. RESULTS: Multiple
      logistic regression analysis indicated that low autonomous regulation or low
      'goal ownership' was the best predictor of drop-out. CONCLUSION: It is suggested
      that the assessment of 'goal ownership' prior to a weight reduction intervention
      could identify patients who are sufficiently motivated to participate. Patients
      who score low on 'goal ownership' may be offered pretreatment interventions to
      increase their motivation.

PMID- 20033630
TI  - Purification of human NK cell developmental intermediates from lymph nodes and
      tonsils.
AB  - Accumulating data indicate that human natural killer (NK) cells undergo terminal
      maturation in secondary lymphoid tissues (SLTs) including lymph nodes (LNs) and
      tonsils. In addition, recent studies have revealed that maturing NK cells
      progress through at least five functionally discrete stages of development within
      SLTs. These discoveries provide unique possibilities for researchers to
      investigate the natural processes governing human NK cell development, as they
      exist in vivo, through analysis of NK cell maturational intermediates found in
      situ. Herein we describe a detailed, yet simple, four-step protocol for the
      viable enrichment and purification of human NK cell developmental intermediates
      from LNs and tonsils.

PMID- 20033631
TI  - In vitro development of human Killer-Immunoglobulin Receptor-positive NK cells.
AB  - The in vitro culture system outlined in this chapter allows for the delineation
      of events that occur during the development of CD34(+) hematopoietic precursor
      cells into mature KIR(+) human NK cells. This system can also be utilized to
      study the effects of gene overexpression or knockdown on the process of NK cell
      differentiation through retroviral transduction and long-term culture. The
      necessary soluble factors and contact-dependent conditions for in vitro human NK
      cell development have been worked out in our laboratory over the past 16 years.

PMID- 20033632
TI  - Subset analysis of human and mouse mature NK cells.
AB  - Identification of natural killer (NK) cell subsets has gained attention with the
      recent discovery that mature mouse NK cells comprise two distinct stages.
      Delineation of the stages is performed using the markers CD27 and CD11b on gated
      NK cells. The significance of this finding is underpinned by recent discoveries
      that mature human NK cells can also be discriminated by differential expression
      of CD27. This chapter will describe the methods required for the purification of
      lymphocytes from blood and other organs and the delineation of NK cell subsets by
      flow cytometry.

PMID- 20033633
TI  - Assessing licensing of NK cells.
AB  - Natural killer (NK) cells express receptors to detect and kill target cells based
      on expression of target cell surface molecules. Through a process termed NK cell
      licensing, only NK cells that express inhibitory receptors (e.g., Ly49 receptors
      in the mouse) for self-major histocompatibility complex (MHC) class I molecules
      become functionally competent to be triggered through their activation receptors.
      To determine the licensing status of particular Ly49(+) murine NK cell subsets,
      splenocytes are stimulated with plate-bound anti-NK1.1 monoclonal antibody in the
      presence of brefeldin A and then assessed for NK cell activation on a single-cell
      basis using intracellular cytokine interferon-gamma staining and flow cytometry.

PMID- 20033634
TI  - Use of stem cell radiation chimeras to analyze how domains of specific proteins
      impact on murine NK cell development in vivo.
AB  - Although the use of mutant mice has been extremely useful in identifying those
      proteins and molecules specifically required for the development of NK cells, the
      establishment of a well-defined protocol to replicate in vitro the major steps
      corresponding to the process of NK cell differentiation and maturation has
      enabled us to dissect the molecular events governing certain aspects of NK cell
      development. This chapter describes a protocol that combines both the use of
      mutant mice and the in vitro bone marrow (BM) culture system for examining the
      role of proteins and their putative signaling domains in NK cell development. BM
      derived Lin-c-kit(+) stem cells expressing the protein of interest are first
      cultured for 6 days in a cocktail of cytokines that promote lymphoid development.
      The semi-differentiated cells are then transplanted into mice to complete their
      development in vivo. While all hematopoietic lineages can develop from these
      transplanted cells, we focus primarily on assessing the effect of the protein on
      the production of NK cells, as well as the acquisition of Ly49 receptors. The
      most prevalent advantage of this method is the ability to potentially link
      signaling regulators to known aspects of NK cell development.

PMID- 20033636
TI  - Natural killer cell conjugate assay using two-color flow cytometry.
AB  - This flow cytometry-based method is a quick way to detect adhesion of NK cells to
      target cells. The two cell types are labeled with distinct fluorescent dyes and
      following co-incubation, the number of NK cells firmly adhered to target cells is
      quantified using two-color flow cytometry.

PMID- 20033635
TI  - Use of transfected Drosophila S2 cells to study NK cell activation.
AB  - Determining the contribution of individual receptors to natural killer (NK) cell
      function is complicated by the multiplicity of activating and inhibitory NK cell
      receptors. Mammalian target cells typically express a variety of ligands for NK
      cell receptors. Engagement of NK cell receptors by antibodies may not mimic
      activation by natural ligands. To define requirements for activation and dissect
      the contribution of receptors to NK cell function, we have generated Drosophila
      Schneider line 2 (S2) cell transfectants expressing ligands for NK cell
      receptors. The evolutionary distance between Drosophila and mammals greatly
      reduces the potential of recognition of insect cell molecules by mammalian NK
      cells. Here, we present methods for maintenance and transfection of S2 cells, as
      well as protocols for their use in NK cell assays.

PMID- 20033637
TI  - Studying NK cell/dendritic cell interactions.
AB  - Although NK cells were originally identified as "naturally" active cells believed
      to follow a cell-autonomous activation program, it is now widely accepted that NK
      cells need to interact with dendritic cells for their full functional activation
      and for their homeostasis. In this chapter, we will provide an experimental guide
      to the analysis of NK cell/DC interactions in vitro and in vivo. We have put
      special emphasis on the recently developed mouse models allowing the inducible
      and specific ablation of various subsets of DCs and other myeloid cells.

PMID- 20033638
TI  - Analysis of the NK cell immunological synapse.
AB  - Since NK cells specialize in contact-dependent functions including cytotoxicity,
      interest has focused on the direct study of the interface between the NK cell and
      the cell with which it is interacting. This interface is also known as the
      immunological synapse and is characterized by an extraordinary number of dynamic
      molecular events that have the potential to result in NK cell function. Here we
      describe microscopy-based methods for evaluating and quantifying the NK cell
      immunological synapse that can be useful in enabling experimental studies.

PMID- 20033639
TI  - Measuring intracellular calcium signaling in murine NK cells by flow cytometry.
AB  - This chapter describes a method by which activating receptor-mediated calcium
      signaling can be measured in individual murine NK cells using a flow cytometer
      fitted with a UV laser. One major advantage of this method is that the calcium
      response of the minority NK cell population and even smaller NK cell
      subpopulations can be measured simultaneously from a mixture of freshly prepared
      total splenocytes without resorting to prior cell sorting or expansion in
      culture. Briefly, cells are harvested and stained to mark the populations of
      interest, then loaded with indo-1 AM dye and analyzed on the flow cytometer.
      After an appropriate baseline is established, the cells are treated with a
      biotinylated antibody to activating receptors, which are subsequently cross
      linked by addition of streptavidin. The increase in intracellular calcium is
      quantified by measuring a shift in the indo-1 emission spectrum that takes place
      when the dye becomes bound to calcium.

PMID- 20033640
TI  - Intracellular staining for analysis of the expression and phosphorylation of
      signal transducers and activators of transcription (STATs) in NK cells.
AB  - Cytokines stimulate biological responses by activating intracellular signaling
      pathways. We have been adapting flow cytometric techniques to measure the levels
      of expression and activation of signaling molecules within mixed populations
      containing NK cells and to characterize their differences within NK cell
      subpopulations. Approaches for evaluating the total levels of the signal
      transducers and activators of transcription STAT1 and STAT4, of STAT1 in cells
      expressing IFNgamma, and of the type 1 interferon (type 1 IFN) activation by
      phosphorylation, i.e., induction of pSTAT1 and pSTAT4, have been developed. The
      results of experiments using these techniques have demonstrated that an unusual
      feature of NK cells is high basal expression of STAT4 but reduced STAT1 levels.
      The condition predisposes for pSTAT4 activation by type 1 IFNs. The work has also
      shown, however, that total STAT1 levels are induced during viral infections as a
      result of IFN exposure, and that this change acts to promote the activation of
      STAT1 but limit both the activation of STAT4 and IFNgamma expression. The
      intracellular staining approaches used for the studies described here have
      utility in characterizing other mechanisms regulating cytokine-mediated
      signaling, and defining additional pathways shaping cellular responses to
      cytokines.

PMID- 20033641
TI  - A model system for studying NK cell receptor signaling.
AB  - Study of NK cell receptor signaling in mouse NK cells has been difficult since
      there are no clones of murine NK cells. We describe here a model system that
      overcomes this problem. This system allows the study of many aspects of NK cell
      receptor function with complete control over the variables that may affect
      activity such as cis versus trans ligand engagement, homotypic interactions,
      multiple target types, receptor number, receptor-ligand affinity, and signaling
      adaptor molecule expression. Although we give examples only for 2B4, Ly49C, and
      CD48, any NK cell receptors could be studied using these methods. Since many NK
      cell receptors such as 2B4, CD48, and the Ly49 family can be expressed in T
      cells, this model system allows the study of not only NK cells but also T cells
      with NK cell receptors. A standardized system for determining the regulation of
      NK cell receptor signaling can be important for understanding the anti-tumor
      activities of NK cells.

PMID- 20033642
TI  - Expression of cDNAs in human Natural Killer cell lines by retroviral
      transduction.
AB  - Human NK-like cell lines are difficult to transfect using standard mammalian
      expression vectors and conventional transfection protocols, but they are
      susceptible to retroviral transduction as a means to introduce cDNAs. Our
      laboratory has exploited this technique to study a number of receptors in human
      NK cell lines. The method utilizes a bicistronic retroviral vector that co
      expresses either drug resistance or enhanced green fluorescent protein (EGFP) in
      parallel with the gene of interest. After a single infection with recombinant
      retrovirus, transduced NK cells can be sorted for expression of EGFP or the
      transduced cell surface marker. Alternatively, cells expressing the transduced
      cDNAs can be selected for by treatment with neomycin, puromycin, or hygromycin.
      Using this method, the sorted/selected cells uniformly express the gene of
      interest and the expression is stable for many weeks of culture.

PMID- 20033643
TI  - Lentiviral gene transduction in human and mouse NK cell lines.
AB  - Natural killer (NK) cells play a vital role in the control of cancer and
      microbial infections. A major hinderance in studying NK cells is the resistance
      of these cells to gene transfer. Considering over-expression and gene knockdown
      studies are crucial tools to study the biology of cells, technologies suitable
      for transferring genes into NK cells are invaluable. Among various technologies
      available for gene transfer, lentiviral-mediated transduction has been successful
      in introducing genes into NK cells. We have standardized methods of lentiviral
      infection in human and mouse NK cell lines. We obtain transduction efficiencies
      of 15% in the NK-92 cell line and 30-40% in LNK, YT, and DERL7 cell lines. This
      method allows efficient and stable introduction of genes and shRNAs into NK cell
      lines.

PMID- 20033644
TI  - Introduction of shRNAs into human NK-like cell lines with retrovirus.
AB  - Natural killer (NK) cell lines are difficult to transfect using standard
      techniques, which limits the ability to establish long-term knockdown of proteins
      with short-hairpin (sh)RNAs. We have developed a method to stably knockdown
      protein expression in human NK-like lines by introducing shRNAs in retroviral
      vectors. After a single transduction with retrovirus, shRNA-containing cells can
      be selected with drug treatment or sorted for enhanced green fluorescent protein
      (EGFP) expression. With this method, protein expression can be stably decreased
      to less than 10% of wild-type levels.

PMID- 20033645
TI  - Introduction of shRNAs into primary NK cells with lentivirus.
AB  - Natural killer (NK) cells are lymphocytes that provide an important line of
      defense against viruses and tumors. Technical hurdles in genetic modifications of
      primary NK cell ex vivo had limited our studies of protein function(s) in NK cell
      differentiation, acquisition of self-tolerance, and induction of anti-tumor
      responses. We used VSV-G-pseudotyped, EGFP-expressing lentiviral vectors to
      develop an efficient gene transfer system to modify gene expression in primary
      murine NK cells with or without prior IL-2 activation. Lentiviral vector
      transduction did not impair NK cellular viability, phenotype, or functions. We
      also demonstrated the use of this system in modifying differentiating NK cells
      derived from lentiviral-transduced murine hematopoietic progenitor cells.
      Furthermore, the same transduction protocol is amendable to delivery of short
      hairpin RNA (shRNA) for specific gene silencing. Collectively, our approach in
      genetic engineering of primary murine NK cells will prove useful in studying
      basic NK cell biology and in exploring therapeutic potentials of NK cells in
      inbred and transgenic mouse models.

PMID- 20033646
TI  - Methods to identify and characterize different NK cell receptors and their
      ligands.
AB  - Different cellular immune responses are modulated by the cross talk between
      activating and inhibitory signaling pathways initiated via different cell surface
      receptors. Similarly, the killing of NK cells is controlled by multiple
      activating and inhibitory surface receptors. In humans, the major NK triggering
      receptors, identified so far, include NKp80, 2B4 NKG2D, and CD16 and the natural
      cytotoxic receptors (collectively named NCRs) include NKp46, NKp44, and NKp30.
      The two major families of MHC-specific inhibitory receptors identified in humans
      are the Ig superfamily (KIR and LIR) and the C-type lectin (CD94/NKG2A) receptor
      superfamily. The different inhibitory receptors show diverse specificity and
      discriminate between different class I MHC proteins. Much is known about the
      function and expression patterns of the different NK cell receptors, but the
      ligand identity of several of the activating NK cell receptors is yet to be
      discovered. This chapter introduces several research tools that can be used to
      uncover the identities of different ligands for NK cell receptors.

PMID- 20033647
TI  - Generating NK cell receptor-Fc chimera proteins from 293T cells and
      considerations of appropriate glycosylation.
AB  - The use of recombinant receptors as a scientific tool has become widespread in
      many research fields. Of particular interest are the natural killer (NK)
      receptors that play a major role in the immune response against tumors and virus
      infected cells. We present here (i) a detailed protocol for the production and
      purification of soluble recombinant NK cell receptors tagged with human IgG1-Fc
      (thus termed receptor-Fc chimera or receptor-Ig fusion protein) and (ii) a
      protocol for cell staining with these recombinant receptor-Fc chimeras. As these
      recombinant proteins are produced in eukaryotic cells, we further discuss the
      glycosylation pattern of these receptors that might interfere with their ligand
      binding phenotype.

PMID- 20033648
TI  - Identification of NK cell receptor ligands using a signaling reporter system.
AB  - NK cell responses are regulated by a balance of inhibitory and activating
      signals, reflecting the net effect of interactions between receptors and ligands
      on target and effector cell surfaces. The identification of ligands for orphan NK
      cell receptors is key to enhancing our understanding of NK cell biology. Here we
      describe a strategy (protocol) for the identification of ligands for orphan NK
      cell receptors using signaling reporter cells in combination with a virus rescue
      system.

PMID- 20033649
TI  - Determining ligand specificity of Ly49 receptors.
AB  - Ly49 receptors in rodents, like KIR in humans, play an integral role in the
      regulation of NK cell activity. Some inhibitory Ly49 are known to interact with
      specific MHC I alleles to maintain tolerance to self tissues, and NK activation
      is triggered upon the loss of inhibitory signals due to pathological
      downregulation of self MHC I. Although a virally encoded ligand has been
      identified that can trigger NK cytotoxicity through an activating Ly49, some
      activating Ly49 also recognize MHC I and the role of most activating receptors in
      NK effector function remains poorly defined. As many Ly49 remain orphan
      receptors, we describe methods to unambiguously discern receptor-ligand pairs.
      Additionally, we describe a method for the mutagenesis of Ly49 and MHC ligands
      that can be used to define the motifs conferring receptor specificity for their
      ligands. Further elucidation of Ly49 ligands is required to continue to define
      the role of Ly49 in regulating NK cell effector function and may give vital clues
      to the role of KIR in human health and disease.

PMID- 20033650
TI  - Probing the interactions of NK cell receptors with ligand expressed in trans and
      cis.
AB  - Certain receptors on natural killer (NK) cells, which are specific for MHC class
      I (MHC-I) molecules, do not only interact with ligand expressed on opposing cell
      membranes (in trans) but also interact with those on the same cell membrane (in
      cis). Cis interactions have been demonstrated for only a small number of cell
      surface receptors. However, this has not been tested systematically, raising the
      possibility that additional receptors may be able to bind ligand expressed in
      cis. Here we describe a number of approaches to evaluate trans and cis binding of
      the Ly49A NK cell receptor to its H-2D(d) ligand. These procedures should
      facilitate the investigation of cis/trans interactions of other receptor-ligand
      pairs and simplify the analysis of NK cell receptor variants.

PMID- 20033651
TI  - A simple method to measure NK cell cytotoxicity in vivo.
AB  - Natural killer (NK) cells were discovered in the 1970 s and named after their
      naturally occurring cytotoxic activity against tumor cells. It has recently
      become clear that NK cells are not just killers and that malignancy is unlikely
      to be the selective pressure driving the evolution of NK cells. Indeed, NK cells
      secrete a host of cytokines and chemokines that contribute to tissue remodeling
      at the feto-maternal interface and to both innate and adaptive immunity during
      infection. Moreover, in certain conditions, they cannot deliver functions cell
      autonomously, as they require priming from other cells, namely dendritic cells.
      Nevertheless, natural cytotoxicity is still considered an important parameter
      used to evaluate NK cell biology, both in the clinic and in the research lab. In
      this chapter we describe a simple method to quantify spontaneous NK cell
      cytotoxicity in vivo.

PMID- 20033652
TI  - Functional analysis of human NK cells by flow cytometry.
AB  - Natural killer (NK) cells are a subset of lymphocytes that contribute to innate
      immunity through cytokine secretion and target cell lysis. NK cell function is
      regulated by a multiplicity of activating and inhibitory receptors. The advance
      in instrumentation for multi-color flow cytometry and the generation of specific
      mAbs for different epitopes related to phenotypic and functional parameters have
      facilitated our understanding of NK cell responses. Here, we provide protocols
      for flow cytometric evaluation of degranulation and cytokine production by human
      NK cells from peripheral blood at the single-cell level. In addition to offering
      insight into the regulation of human NK cell responses, these techniques are
      applicable to the assessment of various clinical conditions, including the
      diagnosis of immunodeficiency syndromes.

PMID- 20033653
TI  - Analysis of the KIR repertoire in human NK cells by flow cytometry.
AB  - Human natural killer (NK) cells are regulated by a diverse receptor repertoire.
      This makes multi-color flow cytometry-based approaches highly attractive for
      detailed phenotypical evaluation of NK cells. Several functional parameters can
      also be evaluated using this technology. In the present chapter, we demonstrate
      the applicability of this technology for the analysis of the human killer cell Ig
      like receptor (KIR) repertoire. We present an antibody panel allowing
      simultaneous assessment of the four major inhibitory KIRs and NKG2A. We further
      provide guidance on how to apply standard operating procedures to multi-color
      flow cytometry experiments. Finally, we discuss possibilities as well as
      limitations with the application of multi-color flow cytometry techniques to
      future studies of human NK cells.

PMID- 20033654
TI  - KIR genotyping by multiplex PCR-SSP.
AB  - Diversity across KIR haplotypes stems from differences in numbers of inhibitory
      and activating receptors, as well as allelic polymorphism of individual genes.
      The KIR locus has undergone large expansions and contractions over time and is
      believed to be coevolving with genes encoding its HLA class I ligands located
      within the MHC locus. KIR and HLA compound genotypes have been associated with
      susceptibility to or protection from infectious, autoimmune, reproductive, and
      malignant disorders. We describe here a simple and reliable multiplex PCR-SSP
      (sequence-specific priming) method for relatively rapid and inexpensive
      genotyping of 15 KIR genes using standard agarose gel electrophoresis.

PMID- 20033655
TI  - Identification and analysis of novel transcripts and promoters in the human
      killer cell immunoglobulin-like receptor (KIR) genes.
AB  - This chapter describes the techniques our lab has used to find the multiple
      promoters present in individual KIR genes. Our previous studies in the murine
      Ly49 gene family led us to expect the presence of distal promoters, antisense
      transcripts, and bi-directional promoters in the KIR gene cluster. We present
      here all of the techniques used to systematically determine if a gene possesses
      these types of control elements.

PMID- 20033656
TI  - Use of inbred mouse strains to map recognition receptors of MCMV infected cells
      in the NK cell gene locus.
AB  - Genetically distinct inbred strains of mice that differ in their susceptibility
      to mouse cytomegalovirus (MCMV) are invaluable for dissecting complex host
      pathogen interactions. Their study has allowed the identification of host
      resistance loci, including several activating NK cell receptors of major
      histocompatibility complex (MHC) class I. In this chapter, we provide a practical
      guide to the genetic mapping and functional characterization of NK cell receptors
      that control innate immunity against MCMV via specific recognition of infected
      cells.

PMID- 20033657
TI  - Studying NK cell responses to ectromelia virus infections in mice.
AB  - Here we describe methods for the in vivo study of antiviral NK cell responses
      using the mouse Orthopoxvirus ectromelia virus as a model, the agent of mousepox.
      The methods include those specific for the preparation and use of ectromelia
      virus such as the production of virus stocks in tissue culture and in live mice,
      the purification of virus stocks, the titration of virus stocks and virus loads
      in organs, and the infection of mice. The chapter also includes methods for the
      specific study of NK cell responses in infected mice such as the preparation of
      organs (lymph nodes, spleen, and liver) for analysis, the study of NK cell
      responses by flow cytometry, the adoptive transfer of NK cells, the measurement
      of NK cell cytolytic activity ex vivo and in vivo, and the determination of NK
      cell proliferation by bromodeoxyuridine loading or by dilution of
      carboxyfluorescein diacetate succinimidyl ester (CFSE).

PMID- 20033658
TI  - Activation of human NK cells by malaria-infected red blood cells.
AB  - This chapter describes a protocol to assess activation of human NK cells
      following in vitro stimulation with malaria-infected red blood cells. Activation
      is assessed by flow cytometry, staining for cell surface expression of CD69 and
      accumulation of intracellular IFN-gamma. Procedures are described for in vitro
      propagation and purification of Plasmodium falciparum parasites, separation of
      peripheral blood mononuclear cells from heparinised blood by density
      centrifugation, in vitro culture of PBMC and for staining and analysis of PBMC by
      flow cytometry. Some examples of typical FACS plots are shown.

PMID- 20033659
TI  - Natural killer cells in human pregnancy.
AB  - Natural killer (NK) cells account for 70% of the leukocytes in the mucosal lining
      of the uterus (the decidua) in the first trimester of pregnancy. They are
      CD56(superbright) granulated cells expressing a repertoire of Killer-cell
      Immunoglobulin-like Receptors (KIR) skewed towards recognising HLA-C, which is
      the only classical class I MHC found on placental trophoblast cells. The function
      of decidual NK cells is not yet known, but there is evidence to suggest that they
      are involved in mediating trophoblast invasion into the decidua and modifying
      maternal spiral arteries to increase blood flow to the placenta. In order to
      characterise decidual NK cells and to understand their interactions with other
      cells at the maternal-foetal interface, it is useful to be able to isolate these
      cells. Here, we describe methods for the isolation and culture of decidual NK
      cells, decidual stromal cells and trophoblast cells from human first trimester
      tissue samples.

PMID- 20033660
TI  - Analysis of uterine natural killer cells in mice.
AB  - The term uterine natural killer (uNK) cell is applied in mice to an abundant but
      transient NK cell population that undergoes unique, terminal differentiation
      within embryo implantation sites during endometrial decidualization and
      pregnancy. In mice, decidualization is induced by attachment and implantation of
      hatched, blastocyst-stage embryos. Within each implantation site, uNK cells
      proliferate and rapidly differentiate into highly restricted regions called
      decidua basalis and the mesometrial lymphoid aggregate of pregnancy (MLAp). uNK
      cells begin to die within healthy decidua basalis by day 8 of the 19-20 day
      pregnancy of mice. By gestation day 12, uNK cell numbers have peaked and most uNK
      cells show in situ nuclear fragmentation indicative of disintegration.
      Morphological studies (standard histology, ultrastructure, immunohistochemistry,
      in situ hybridization, and RNA analyses from laser capture microdissected uNK
      cells) have provided most of the current understanding regarding this cell
      lineage. These approaches identified the special angiogenic properties of uNK
      cells and their regulatory relationships with normal physiological changes to the
      uterine (endometrial) arterial tree that accompany successful pregnancy. This
      chapter highlights key information needed for successful dissection of the
      dynamically changing decidua basalis that is enriched in uNK cells and special
      morphological procedures used for uNK cell study. Preparation of viable mouse uNK
      cell suspensions is difficult but can be achieved. This chapter includes
      techniques for isolation of uterine leukocyte suspensions and their enrichment
      for uNK cells that permit immediate downstream applications such as culture,
      isolation of high quality RNA, or flow cytometry.

PMID- 20033661
TI  - Isolation of NK cells and NK-like cells from the intestinal lamina propria.
AB  - Being exposed to food products, pathogens and harmless commensal bacteria, the
      mucosal immune system faces a constant challenge. Therefore, maintenance of a
      homeostatic balance is required to achieve tolerance to harmless bacteria and
      their products and to induce potent immunity to infection with pathogenic
      bacteria. Until recently, the literature on mucosal natural killer (NK) cells
      residing in the intestinal lamina propria was scarce and phenotype and function
      of gut mucosal NK cells did not receive much attention. Recently, data have
      become available identifying two distinct subsets of mucosal NKp46(+) lymphocytes
      based on the expression of the orphan transcription factor RORgammat. In many
      ways, the RORgammat(-) subset resembled "classical" NK cells in that it was
      developmentally dependent on IL-15 but not on RORgammat and displayed NK cell
      function (e.g., cell-mediated cytotoxicity, IFN-gamma production). In contrast,
      the RORgammat(+) subset developed independent of IL-15 but required RORgammat,
      suggesting that this subset may be related to lymphoid tissue inducer (LTi)
      cells. Interestingly, these RORgammat(+) NKp46(+) NK-LTi cells constitutively
      produced large amounts of IL-22, a cytokine regulating antimicrobial protection
      and regeneration of epithelial cells. In this chapter, we provide experimental
      procedures to isolate "classical" NK cells from the intestinal lamina propria as
      well as the newly described lymphoid tissue inducer-like (LTi-like) cells
      producing IL-22 and co-expressing NK cell receptors.

PMID- 20033662
TI  - [Regulation (EC) No. 1394/2007 on advanced therapy medicinal products :
      Incorporation into national law].
AB  - Regulation (EC) No. 1394/2007 has created a new legal framework for advanced
      therapy medicinal products (gene therapy medicinal products, somatic cell therapy
      medicinal products and tissue engineered products). The Regulation is directly
      applicable in the Member States of the European Union and, in principle, requires
      no incorporation into national law. However, the amendment of Directive
      2001/83/EC, which results from Regulation (EC) No. 1394/2007, has created a need
      for incorporation into and amendment of the German Medicinal Products Act. This
      is one of the objectives of the 15th amendment of the German Medicinal Products
      Act. In particular, the definition "advanced therapy medicinal products" and the
      special provisions for advanced therapy medicinal products prepared on a non
      routine basis, which are based on the special provisions contained in Art. 28 No.
      2 of Regulation (EC) No. 1394/2007, are to be incorporated into the German
      Medicinal Products Act. These special provisions will be explained in detail.

PMID- 20033663
TI  - [Tobacco prevention in the workplace. Achievements and requirements].
AB  - Tobacco prevention in the workplace is a major area of action within the tobacco
      control measures, since a decisive impetus for social change can derive from the
      working environment. In 2002, the protection of non-smokers in the workplace
      became mandatory in Germany. Since then, the enforcement of the new law has been
      supported by a variety of organizations. However, recent surveys show that almost
      20% of non-smoking employees are still exposed to tobacco smoke. Therefore, it is
      necessary to take stock regarding the enforcement of the law. For one million
      people who currently work in catering, the right for non-smokers' protection is
      limited as the law for non-smokers' protection at work includes an exception for
      bars and restaurants. Tobacco prevention in the workplace will not be complete
      until this exception does not apply anymore. Also, a general smoking ban in bars
      and restaurants would become constitutional through relevant laws. Whether the
      Bundeslander will agree on this ban is doubtful at the moment. The promotion of
      smoking cessation as a second decisive part in tobacco prevention in the
      workplace has not reached the desired importance in company measures. To increase
      the significance of smoking cessation in companies, further impetus is necessary.

PMID- 20033664
TI  - [Smoking cessation therapies in Germany].
AB  - Reducing the consumption of tobacco products in Germany is a health objective
      that is achievable with smoking cessation treatments for smokers. This objective
      turns out to be more successful when using different interventions for smoking
      cessation than with self-initiated smoking cessation methods. This survey
      describes the range of smoking cessation treatments in Germany and evaluates them
      on the basis of international guidelines.

PMID- 20033665
TI  - [Modern neuroimaging of brain plasticity].
AB  - Modern neuroimaging methods offer new insights into the plasticity of the human
      brain. As the techniques of functional MRI and diffusion tensor imaging are
      increasingly being applied in a clinical setting, the examiner is now frequently
      confronted with the interpretation of imaging findings related to regenerative
      processes in response to lesions of the central and also of the peripheral
      nervous system. In this article individual results of modern neuroimaging studies
      are discussed in the context of structural and functional plasticity of the CNS.

PMID- 20033666
TI  - [Erectile dysfunction after radical prostatectomy : patient information, contact
      persons, postoperative proerectile therapy].
AB  - BACKGROUND: Postoperative erectile dysfunction (ED) is one of the potential after
      effects of radical prostatectomy. The aim of this study was to learn which
      caregivers inform the patients prior to the intervention about the risk of ED,
      which individuals the patients discuss this issue with, and whether the patients
      preoperatively consider use of a PDE5 inhibitor for proerectile therapy after the
      operation. METHODS: Using the IIEF-5 questionnaire, the preoperative erectile
      function of 110 patients was evaluated after the hospital admission interview.
      The patients were asked who had informed them about the risk of postoperative ED.
      They were also asked in whom they had confided to discuss this issue and whether
      they were prepared to undergo postoperative proerectile therapy with a PDE5
      inhibitor. The patients were subsequently assigned to one of two groups: group I,
      consisting of those with a preoperative IIEF score > or = 21, or group II, those
      with a preoperative IIEF score <21. RESULTS: The answers given by groups I and II
      did not differ significantly. The median patient age was the same, 68, in both
      groups. In addition to being informed about postoperative ED by the hospital
      doctor on admission (100%), the patients were informed about this by the
      following individuals (results for group II in parentheses): board-certified
      urologist, 81.8% (74%); general practitioner (GP), 27.3%; partner, 12.1% (11.7%);
      self-help groups, 0% (2.6%); and friends, 3% (6.5%). Patients also discussed the
      risk of postoperative ED with the following individuals (results for group II in
      parentheses): local urologist, 66.7% (63.4%); partner, 45.5% (42.9%); hospital
      doctor, 39.4% (42.9%); GP, 21.2% (23.4%); friends, 9.1% (14.3); or no one, 3%
      (5.2%). Regarding whether patients were willing to undergo postoperative therapy
      using a PDE5 inhibitor, 36.4% in group I and 32.5% in group II said yes, 12.1% in
      group I and 11.7% in group II said no, and 51.5% in group I and 55.8% in group II
      were undecided. CONCLUSION: Irrespective of the patient's erectile status, the
      hospital doctor and the local urologist informed the patients about the risk of
      postoperative ED. Satisfactory information delivered by at least two people
      occurred in over 70% of all cases. The most frequent confidant of the patient for
      discussing this issue was his local urologist. Fewer than 50% of the patients
      discussed this topic with their partners. Possible reasons for underestimating
      the importance of sexual function could be the frequent taboo status of sexuality
      as a discussion topic in relationships, as well as preoperative distress. These
      circumstances should be taken into account by offering sufficient information,
      including that on the availability of postoperative proerectile therapy, for both
      the patient and his partner as early as possible, i.e., at the stage of choosing
      a treatment option.

PMID- 20033667
TI  - Enhanced trafficking to the pancreatic lymph nodes and auto-antigen presentation
      capacity distinguishes peritoneal B lymphocytes in non-obese diabetic mice.
AB  - AIMS/HYPOTHESIS: NOD.Igmicro ( null ) mice lacking mature B cells are highly
      resistant to diabetes and display poor CD4 T cell responses to autoantigens.
      Nevertheless, the degree to which different B cell subsets contribute to diabetes
      in NOD mice remains unresolved. Due to their role in the recognition of microbial
      and autoantigens, peritoneal B cell characteristics were examined in NOD mice to
      see if they differ developmentally, phenotypically or functionally in aspects
      relevant to diabetogenesis. METHODS: The population dynamics, activation state,
      migratory behaviour and antigen presentation function were investigated in NOD
      peritoneal B cells. RESULTS: NOD peritoneal B cells were found to express
      abnormally high levels of co-stimulatory molecules (CD40, CD86 and CD69). In
      contrast, the expression of L-selectin and integrin alpha4beta1 was markedly
      reduced in NOD mice compared with BALB/c and C57BL/6 mice. The number of B cells
      in the peritoneum was lower in NOD than in control mice throughout development;
      migration of B cells from the peritoneum to the pancreatic lymph nodes in NOD
      mice was enhanced tenfold. NOD B cells showed no chemotactic response to
      sphingosine-1-phosphate, which normally acts to retain B cells in the peritoneum.
      Peritoneal B cells of NOD mice also presented insulin autoantigen to CD4 T cells,
      inducing T cell proliferation. CONCLUSIONS/INTERPRETATION: NOD peritoneal B cells
      are hyperactivated, migrate to the pancreatic lymph nodes and are capable of
      driving insulin-specific CD4 T cell activation. These characteristics could make
      them important for inducing or amplifying T cell responses against islet
      antigens.

PMID- 20033668
TI  - Extracorporeal life support for treatment of children with enterovirus 71
      infection-related cardiopulmonary failure.
AB  - PURPOSE: Enterovirus 71 (EV71) infection leading to cardiopulmonary failure (CPF)
      is rare, but usually fatal. In such cases, intensive cardiorespiratory support is
      essential for survival. In this study, we report our experience in the treatment
      of EV71-related CPF with extracorporeal life support (ECLS). METHODS: This was a
      retrospective study of a total of 13 children, aged 16 +/- 10 months, with EV71
      related hemodynamically unstable CPF, which was refractory to conventional
      treatments, who were rescued by transsternal ECLS from 2000 to 2008. The clinical
      manifestations and outcomes of the 13 children (present cohort) were compared
      with those of 10 children (past cohort) who had EV71-related CPF without ECLS
      between 1998 and 2000. RESULTS: Among these 13 patients, 10 were successfully
      weaned off ECLS and survived. The myocardial recovery time was 71 +/- 28 (median,
      69) h, and the ECLS duration was 93 +/- 33 (median, 93) h. Six surviving patients
      had a good neurological outcome at hospital discharge. All surviving patients had
      some neurological sequelae but showed improvement at follow-up, including
      dysphagia in nine, central hypoventilation in seven, limb weakness in six and
      seizure in three. The present cohort had better neurological outcomes (46 vs. 0%,
      P = 0.005) and a higher survival rate (77 vs. 30%, P = 0.024) than the past
      cohort, respectively. CONCLUSIONS: Patients with EV71-related CPF supported by
      ECLS had a higher survival rate and fewer neurological sequelae than those who
      only received conventional treatments. ECLS is an effective alternative method
      for treatment of children with refractory EV71-related CPF.

PMID- 20033669
TI  - Thromboembolic complications after bilateral knee arthroscopic surgery patients.
AB  - Deep venous thrombosis and pulmonary embolism are rare complications after
      arthroscopic knee procedures. Most of the cases of thromboembolic complications
      reported to have involved unilateral knee arthroscopic patients; here, we report
      the cases of patients with bilateral knee arthroscopy. The patients were treated
      with anticoagulants and thrombolytics and subjected to necessary laboratory
      monitoring. All the patients recovered well after the treatment and were symptom
      free during a 6-month follow-up. The purpose of this article was to increase the
      awareness of knee arthroscopists of this complication.

PMID- 20033670
TI  - Reconstruction of chronic patellar tendon tear with allograft in a patient with
      Ehlers-Danlos syndrome.
AB  - Failure of repair of the patellar tendon is uncommon. It may occur in association
      with chronic systemic diseases or after administration of corticosteroid and
      quinolones. We report the reconstruction of the patellar tendon with allograft,
      after failed primary repair, of a 23-year-old young with Ehlers-Danlos syndrome.

PMID- 20033671
TI  - Extensor mechanism repair and reconstruction using Achilles tendon allograft
      after bilateral patellar tendon rupture in a patient with rheumatoid arthritis.
AB  - Here we report spontaneous rupture of the bilateral patellar tendons in a 49-year
      old man with rheumatoid arthritis. The ruptured tendons were sutured via bone
      tunnels using Krackow stitch, and the extensor mechanism of the knee was
      reinforced with three bundles of allograft Achilles tendons. The patient
      recovered well after operation. He could actively flex, extend the knees and
      carry out full-weight-bearing activities, and he resumed the former employment 6
      months after the operation. Follow-up showed that the patient had satisfactory
      range of motion of the knees 1 year later.

PMID- 20033672
TI  - Accuracy of high tibial osteotomy: comparison between open- and closed-wedge
      technique.
AB  - High tibial osteotomy is an established technique for the treatment of varus
      malaligned knees. This study analyses the difference between the amount of
      correction in the preoperative planning and the postoperative result.
      Furthermore, it compares the difference of the accuracy between open-wedge
      osteotomy and closed-wedge osteotomy. About 61 patients were either treated with
      open-wedge or closed-wedge high tibial osteotomy. Preoperative planning and
      postoperative analysis were performed with a special planning software. The
      influence of operative technique, aetiology, age, number of previous surgeries,
      amount of correction and accuracy of the correction compared to the preoperative
      planning were analysed. The overall postoperative mechanical axis differed form
      preoperative planning by 2.1 degrees  +/- 1.7 degrees . The accuracy in the open
      wedge group (1.7 degrees  +/- 1.6 degrees ) was significantly higher than in the
      closed-wedge group (2.6 degrees  +/- 1.8 degrees ; P = 0.038). In patients with
      congenital varus deformity, the accuracy of the correction was significantly
      higher than in patients with post-traumatic deformity. The authors recommend open
      wedge technique in combination with fixed-angle plates for high tibial osteotomy.

PMID- 20033673
TI  - Humeral head osteonecrosis following arthroscopic rotator cuff repair.
AB  - Humeral head chondrolysis and osteonecrosis of the glenoid have been reported;
      however, there is no report to date about humeral head osteonecrosis following
      arthroscopic shoulder procedure. We report a case of osteonecrosis of the humeral
      head following arthroscopic rotator cuff repair what we believe is probably
      secondary to disruption of its blood supply after placement of multiple metallic
      suture anchors. The surgical records were also reviewed in an attempt to identify
      the cause of the humeral head osteonecrosis.

PMID- 20033674
TI  - Effect of in vitro culture on a chondrocyte-fibrin glue hydrogel for cartilage
      repair.
AB  - Research in tissue engineering has been focused on articular cartilage repair for
      more than a decade. Some pioneristic studies involved the use of hydrogels such
      as alginate and fibrin glue which still possess valuable potential for cartilage
      regeneration. One of the main issues in cartilage tissue engineering is
      represented by the ideal maturation of the construct, before in vivo
      implantation, in order to optimize matrix quality and integration. The present
      study was focused on the effect of in vitro culture on a fibrin glue hydrogel
      embedding swine chondrocytes. We performed an evaluation of the
      immunohistochemical and biochemical composition and of the biomechanical
      properties of the construct after 1 and 5 weeks of culture. We noticed that
      chondrocytes survived in the fibrin glue gel and enhanced their synthetic
      activity. In fact, DNA content remained stable, while all indices of cartilage
      matrix production increased (GAGs content, immunohistochemistry for collagen II
      and safranin-o staining). On the other hand, the biomechanical properties
      remained steady, indicating a gradual substitution of the hydrogel scaffold by
      cartilaginous matrix. This demonstrates that an optimal preculture could provide
      the surgeon with a better engineered cartilage for implantation. However, whether
      this more mature tissue will result in a more efficient regeneration of the
      articular surface still has to be evaluated in future investigations.

PMID- 20033675
TI  - Does bracing influence brain activity during knee movement: an fMRI study.
AB  - Studies have shown that proprioceptive inputs during active and passive arm
      movements are processed in the primary and secondary somatosensory cortex and
      supplementary motor area of the brain. At which level of the central nervous
      system proprioceptive signals coming from the knee are regulated remains to be
      elucidated. In order to investigate whether there is a detectable difference in
      brain activity when various proprioceptive inputs are exerted at the knee,
      functional magnetic resonance imaging (fMRI) was used. fMRI in 13 healthy, right
      leg-dominant female volunteers compared brain activation during flexion-extension
      movements of the right knee under three different conditions: with application of
      a tight knee brace, with application of a moderate tight knee sleeve, and without
      application of a brace or sleeve. Brain activation was detected in the primary
      sensorimotor cortex (left and right paracentral lobule) and in the left superior
      parietal lobule of the brain. There was a significantly higher level of brain
      activation with the application of the brace and sleeve, respectively, compared
      to the condition without a brace or sleeve. A significantly higher cortical
      activation was also seen when comparing the braced condition with the condition
      when a sleeve was applied. The results suggest that peripheral proprioceptive
      input to the knee joint by means of a brace or sleeve seems to influence brain
      activity during knee movement. The results of this study also show that the
      intensity of brain activation during knee movement can be influenced by the
      intensity of proprioceptive stimulation at the joint.

PMID- 20033676
TI  - Can patients really do sport after TKA?
AB  - Function and sport participation was analyzed via a self-administered
      questionnaire in 347 patients with unilateral noncomplicated TKA. It was 227
      women and 120 men with a mean age of 75 (range, 28 to 94) and a mean follow-up of
      44 months (range 13-71). Two hundred and thirty-seven patients (68%) reported
      that their knee was "normal", 56% that their activities were limited by their
      knee, and 66% that they were as active as they expected to be before the
      intervention. Of them, 98% were satisfied. Of the patients who were
      insufficiently active, 52% were not satisfied with their outcome (P < 0.0001).
      Neither the duration of preoperative pain, the age at evaluation or the number of
      previous surgeries influenced the subjective result or the degree of patient
      satisfaction. Among patients under 75 years, 10% regularly participated in
      strenuous sports but only 13% felt that this ability was important. When
      participation was analyzed in the motivated patients subgroup, 63% regularly took
      part in at least one impact sport.

PMID- 20033678
TI  - SERS as tool for the analysis of DNA-chips in a microfluidic platform.
AB  - A sequence-specific detection method of DNA is presented combining a solid chip
      surface for immobilisation of capture DNAs with a microfluidic platform and a
      readout of the chip based on SERS. The solid chip surface is used for
      immobilisation of different capture DNAs, where target strands can be hybridised
      and unbound surfactants can be washed away. For the detection via SERS, short
      labelled oligonucleotides are hybridised to the target strands. This technique is
      combined with a microfluidic platform that enables a fast and automated
      preparation process. By applying a chip format, the problems of sequence-specific
      DNA detection in solution phase by means of SERS can be overcome. With this
      setup, we are able to distinguish between different complementary and non
      complementary target sequences in one sample solution.

PMID- 20033679
TI  - Detection of negative ions in glow discharge mass spectrometry for analysis of
      solid specimens.
AB  - A new method is presented for elemental and molecular analysis of halogen
      containing samples by glow discharge time-of-flight mass spectrometry, consisting
      of detection of negative ions from a pulsed RF glow discharge in argon. Analyte
      signals are mainly extracted from the afterglow regime of the discharge, where
      the cross section for electron attachment increases. The formation of negative
      ions from sputtering of metals and metal oxides is compared with that for
      positive ions. It is shown that the negative ion signals of F(-) and TaO(2)F(-)
      are enhanced relative to positive ion signals and can be used to study the
      distribution of a tantalum fluoride layer within the anodized tantala layer.
      Further, comparison is made with data obtained using glow-discharge optical
      emission spectroscopy, where elemental fluorine can only be detected using a neon
      plasma. The ionization mechanisms responsible for the formation of negative ions
      in glow discharge time-of-flight mass spectrometry are briefly discussed.

PMID- 20033680
TI  - Timing variability and not force variability predicts the endpoint accuracy of
      fast and slow isometric contractions.
AB  - The purpose of the study was to determine the contributions of endpoint variance
      and trajectory variability to the endpoint accuracy of goal-directed isometric
      contractions when the target force and contraction speed were varied. Thirteen
      young adults (25 +/- 6 years) performed blocks of 15 trials at each of 2
      contraction speeds and 4 target forces. Subjects were instructed to match the
      peak of a parabolic force trajectory to a target force by controlling the
      abduction force exerted by the index finger. The time to peak force was either
      150 ms (fast) or 1 s (slow). The target forces were 20, 40, 60, and 80% of the
      maximal force that could be achieved in 150 ms during an MVC. The same absolute
      forces were required for both contraction speeds. Endpoint accuracy and
      variability in force and time along with intramuscular EMG activity of the
      agonist (first dorsal interosseus) and antagonist (second palmar interosseus)
      muscles were quantified for each block of trials. The principal dependent
      variables were endpoint error (shortest distance between the coordinates of the
      target and the peak force), endpoint variance (sum of the variance in peak force
      and time to peak force), trial-to-trial variability (SD of peak force and time to
      peak force), SD of the force trajectory (SD of the detrended force from force
      onset to peak force), normalized peak EMG amplitude, and the SD of normalized
      peak EMG amplitude. Stepwise multiple linear regression models were used to
      determine the EMG activity parameters that could explain the differences observed
      in endpoint error and endpoint variance. Endpoint error increased with target
      force for the fast contractions, but not for the slow contractions. In contrast,
      endpoint variance was greatest at the lowest force and was not associated with
      endpoint error at either contraction speed. Furthermore, force trajectory SD was
      not associated with endpoint error or endpoint variance for either contraction
      speed. Only the trial-to-trial variability of the timing predicted endpoint
      accuracy for fast and slow contractions. These findings indicate that endpoint
      error in tasks that require force and timing accuracy is minimized by controlling
      timing variability but not force variability, and that endpoint error is not
      related to the amplitude of the activation signal.

PMID- 20033681
TI  - Atazanavir plasma concentrations are impaired in HIV-1-infected adults
      simultaneously taking a methadone oral solution in a once-daily observed therapy
      setting.
AB  - OBJECTIVE: The human immundeficiency virus (HIV) protease inhibitor atazanavir is
      often used in once-daily observed therapy of methadone substituted former opiate
      drug users. We performed a matched-pairs analysis on 24 patients (12 men/women)
      taking atazanavir/ritonavir 300/100 mg daily plus reverse transcriptase
      inhibitors, with (n = 12) or without (n = 12) methadone co-administration.
      METHODS: Twenty-four-hour pharmacokinetic profiles of atazanavir/ritonavir were
      assessed at steady-state and measured by liquid chromatography-tandem mass
      spectrometry. The geometric mean (GM, t test) minimum and maximum plasma drug
      concentrations (C(min), C(max)), area under the concentration-time curve (AUC),
      and total clearance (CL(total)) were compared between the groups of pairs, which
      were matched for age, sex, weight, and ethnicity. RESULTS: The GM [90% confidence
      interval (CI)] of the atazanavir C(min), C(max), and AUC of patients taking the
      methadone oral solution at doses of 20-175 mg/day simultaneously with
      antiretroviral therapy were impaired compared to patients not taking methadone
      oral solution: C(min) = 315 (range 197-448) vs. 519 (279-793) ng/mL [GM ratio
      (GMR) = 0.61, p = 0.229]; C(max) = 1714 (1238-2262) vs. 3190 (2412-4076) ng/mL
      (GMR = 0.54, p = 0.018); AUC = 21,987 (15,870-29,327) vs. 35,572 (26,211-46,728)
      ng h/mL (GMR = 0.62, p = 0.074). Methadone dose, which is proportional to the
      amount of methadone oral solution (10 mg/mL), was significantly correlated to
      atazanavir C(max) (r (2) = 0.40, p = 0.001) and AUC (r (2) = 0.32, p = 0.006).
      Ritonavir pharmacokinetics was similar between the groups with C(min), C(max),
      and AUC GMR of 1.01, 0.80, and 0.96, respectively. CONCLUSION: The partial
      decrease in atazanavir plasma concentrations in patients concomitantly taking
      racemic methadone oral solution in this daily observed therapy setting deserves
      further attention, and therapeutic drug monitoring should be considered.

PMID- 20033683
TI  - Yttrium-90 radioembolization in the management of liver tumors: expanding the
      global experience.

PMID- 20033682
TI  - Genetic and genomic dissection of cardiogenesis in the Drosophila model.
AB  - The linear heart tube of the fruit fly Drosophila has served as a very valuable
      model for studying the regulation of early heart development. In the past,
      regulatory genes of Drosophila cardiogenesis have been identified largely through
      candidate approaches. The vast genetic toolkit available in this organism has
      made it possible to determine their functions and build regulatory networks of
      transcription factors and signaling inputs that control heart development. In
      this review, we summarize the major findings from this study and present current
      approaches aiming to identify additional players in the specification,
      morphogenesis, and differentiation of the heart by forward genetic screens. We
      also discuss various genomic and bioinformatic approaches that are currently
      being developed to extend the known transcriptional networks more globally which,
      in combination with the genetic approaches, will provide a comprehensive picture
      of the regulatory circuits during cardiogenesis.

PMID- 20033684
TI  - Kinetic analysis of the cannabinoid-1 receptor PET tracer [(18)F]MK-9470 in human
      brain.
AB  - PURPOSE: Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens
      perspectives for many neurological and psychiatric disorders. We characterized
      the kinetics and reproducibility of the CB1R tracer [(18)F]MK-9470 in human
      brain. METHODS: [(18)F]MK-9470 data were analysed using reversible models and the
      distribution volume V (T) and V (ND) k (3) (V (ND) k (3) = K (1) k (2)) were
      estimated. Tracer binding was also evaluated using irreversible kinetics and the
      irreversible uptake constant K (i) and fractional uptake rate (FUR) were
      estimated. The effect of blood flow on these parameters was evaluated.
      Additionally, the possibility of determining the tracer plasma kinetics using a
      reduced number of blood samples was also examined. RESULTS: A reversible two
      tissue compartment model using a global k (4) value was necessary to describe
      brain kinetics. Both V (T) and V (ND) k (3) were estimated satisfactorily and
      their test-retest variability was between 10% and 30%. Irreversible methods
      adequately described brain kinetics and FUR values were equivalent to K (i). The
      linear relationship between K (i) and V (ND) k (3) demonstrated that K (i) or FUR
      and thus the simple measure of tracer brain uptake provide CB1R availability
      information. The test-retest variability of K (i) and FUR was <10% and estimates
      were independent of blood flow. Brain uptake can be used as a receptor
      availability index, albeit at the expense of potential bias due to between
      subject differences in tracer plasma kinetics. CONCLUSION: [(18)F]MK-9470
      specific binding can be accurately determined using FUR values requiring a short
      scan 90 to 120 min after tracer administration. Our results suggest that
      [(18)F]MK-9470 plasma kinetics can be assessed using a few venous samples.

PMID- 20033685
TI  - Dosimetry-guided high-activity (131)I therapy in patients with advanced
      differentiated thyroid carcinoma: initial experience.
AB  - PURPOSE: In patients with advanced differentiated thyroid carcinoma (DTC),
      therapy with the highest safe (131)I activity is desirable to maximize the tumour
      radiation dose yet avoid severe myelotoxicity. Recently, the European Association
      of Nuclear Medicine (EANM) published a standard operational procedure (SOP) for
      pre-therapeutic dosimetry in DTC patients incorporating a safety threshold of a 2
      Gy absorbed dose to the blood as a surrogate for the red marrow. We sought to
      evaluate the safety and effectiveness in everyday tertiary referral centre
      practice of treating advanced DTC with high (131)I activities chosen primarily
      based on the results of dosimetry following this SOP. METHODS: We retrospectively
      assessed toxicity as well as biochemical and scintigraphic response in our first
      ten patients receiving such therapy for advanced DTC. RESULTS: The 10 patients
      received a total of 13 dosimetrically guided treatments with a median
      administered activity of 14.0 GBq (range: 7.0-21.4 GBq) (131)I. After 6 of 13
      treatments in 6 of 10 patients, short-term side effects of (131)I therapy, namely
      nausea, vomiting or sialadenitis, were observed. Leukocyte and platelet counts
      dropped significantly in the weeks after (131)I treatment, but returned to pre
      treatment levels by 3 months post-therapy. Serum thyroglobulin levels decreased
      after 12 of 13 treatments (median reduction: 58%) in 9 of 10 patients.
      CONCLUSION: In our initial patient cohort, high-activity (131)I therapy for
      advanced DTC based on pre-therapeutic blood dosimetry following the EANM SOP was
      safe and well tolerated. Such treatment almost always produced a partial
      biochemical tumour response.

PMID- 20033686
TI  - How can we make progress with decision support systems in landscape and river
      basin management? Lessons learned from a comparative analysis of four different
      decision support systems.
AB  - This article analyses the benefits and shortcomings of the recently developed
      decision support systems (DSS) FLUMAGIS, Elbe-DSS, CatchMODS, and MedAction. The
      analysis elaborates on the following aspects: (i) application area/decision
      problem, (ii) stakeholder interaction/users involved, (iii) structure of
      DSS/model structure, (iv) usage of the DSS, and finally (v) most important
      shortcomings. On the basis of this analysis, we formulate four criteria that we
      consider essential for the successful use of DSS in landscape and river basin
      management. The criteria relate to (i) system quality, (ii) user support and user
      training, (iii) perceived usefulness and (iv) user satisfaction. We can show that
      the availability of tools and technologies for DSS in landscape and river basin
      management is good to excellent. However, our investigations indicate that
      several problems have to be tackled. First of all, data availability and
      homogenisation, uncertainty analysis and uncertainty propagation and problems
      with model integration require further attention. Furthermore, the appropriate
      and methodological stakeholder interaction and the definition of 'what end-users
      really need and want' have been documented as general shortcomings of all four
      examples of DSS. Thus, we propose an iterative development process that enables
      social learning of the different groups involved in the development process,
      because it is easier to design a DSS for a group of stakeholders who actively
      participate in an iterative process. We also identify two important lines of
      further development in DSS: the use of interactive visualization tools and the
      methodology of optimization to inform scenario elaboration and evaluate trade
      offs among environmental measures and management alternatives.

PMID- 20033687
TI  - Factors influencing the long-term survival in patients with esophageal cancer who
      underwent esophagectomy after chemoradiotherapy.
AB  - BACKGROUND: Salvage esophagectomy is potentially the only treatment available
      that can offer a chance of long-term survival when definitive chemoradiotherapy
      (CRT) fails to achieve local control for patients with esophageal squamous cell
      carcinoma (ESCC). However, salvage esophagectomy is a highly invasive procedure
      with various postoperative complications compared to planned esophagectomy after
      neoadjuvant chemoradiotherapy (CRT). We hypothesize that severe postoperative
      complications may affect not only surgical mortality but also tumor recurrence
      and long-term survival for patients with salvage esophagectomy after definitive
      CRT. METHODS: For the present study we reviewed the surgical procedures,
      postoperative complications, and the prognosis of 65 consecutive patients with
      thoracic ESCC who underwent the esophagectomy after neoadjuvant (neoadjuvant
      group: n = 40) or definitive (salvage group: n = 25) CRT. RESULTS: Most patients
      underwent right-transthoracic extended esophagectomy and reconstruction using
      gastric conduit by way of subcutaneous route with left cervical anastomosis. The
      incidence of postoperative pneumonia was found to be higher in the salvage group
      than in the neoadjuvant group. In both groups, the survival of patients with R0
      resection was significantly better than those with R1/R2 resection. Moreover, in
      the salvage group, the postoperative survival rate of patients with pneumonia or
      bacteremia/sepsis was significantly lower than that for patients who did not
      suffer the same complications. In the neoadjuvant group, R0 resection was
      selected to be the only independent prognostic factor in univariate and
      multivariate analysis. In contrast, in the salvage group, R0 resection and
      bacteremia/sepsis remained significant and were independent of the other factors
      in multivariate analysis. CONCLUSIONS: This study reveals that postoperative
      morbidity affects not only the perioperative mortality but also the long-term
      survival of patients with ESCC who undergo salvage esophagectomy after definitive
      CRT.

PMID- 20033688
TI  - Thoracic aortic stent-graft placement for safe removal of a malpositioned pedicle
      screw.
AB  - We describe a case of percutaneous placement of a thoracic aortic stent-graft for
      safe removal of a malpositioned pedicle screw in a 52-year-old man. The patient
      had undergone posterior thoracic spinal instrumentation for pyogenic spondylitis
      and spinal deformity 8 months previously. Follow-up CT images showed a
      malpositioned pedicle screw which was abutting the thoracic aorta at the T5
      level. After percutaneous stent-graft placement, the malpositioned pedicle screw
      was safely and successfully removed.

PMID- 20033689
TI  - Delayed development of brain abscesses following stent-graft placement in a head
      and neck cancer patient presenting with carotid blowout syndrome.
AB  - We describe the delayed development of intracranial abscesses following emergent
      treatment with a covered stent-graft for carotid blowout syndrome (CBS) in a
      patient with head and neck cancer. The patient presented with hemoptysis and
      frank arterial bleeding through the tracheostomy site. A self-expandable stent
      graft was deployed across a small pseudoaneurysm arising from the right common
      carotid artery (RCCA) and resulted in immediate hemostasis. Three months later,
      the patient suffered a recurrent hemorrhage. CT of the neck demonstrated
      periluminal fluid around the caudal aspect of the stent-graft with intraluminal
      thrombus and a small pseudoaneurysm. Subsequently, the patient underwent a
      balloon test occlusion study and endovascular sacrifice of the RCCA and right
      internal carotid artery. MRI of the brain demonstrated at least four ring
      enhancing lesions within the right cerebral hemisphere consistent with
      intracranial abscesses that resolved with broad-spectrum antibiotic coverage.

PMID- 20033690
TI  - Retinal embolization during carotid angioplasty and stenting: periprocedural data
      and follow-up.
AB  - The purpose of this study was to prospectively evaluate the incidence of retinal
      emboli during carotid angioplasty and stenting (CAS) and to correlate emboli with
      clinical findings and transcranial Doppler (TCD)-detected cerebral embolic load.
      Between 2001 and 2005, 33 CAS procedures in 32 patients (23 [72%] male, 19 [58%]
      symptomatic, mean age 72.5 years [range 54.6 to 83.9]) scheduled for CAS were
      included in this study. Bilateral fundoscopy with retinal photography was
      performed by an experienced ophthalmologist immediately before, immediately after
      (fundoscopy only), and 1 day after the procedure and again at long-term follow-up
      (mean 37 months). Visual field testing was performed before CAS and again at long
      term follow-up. TCD-detected cerebral emboli were stratified to five procedural
      phases: wiring, predilatation, stent placement, postdilatation, and cerebral
      protection device (CPD) use (if applicable). To establish correlation between TCD
      data and retinal embolization, Mann-Whitney test was used, and P < 0.05 was
      considered statistically significant. All procedures were performed successfully.
      In five of 33 procedures (15%), new retinal emboli were found. Two of the
      procedures with emboli had small retinal infarcts. Three of five were performed
      using CPDs versus seven of 28 that had no retinal emboli (P = not significant).
      Two of four patients (50%) with previous radiation therapy to the neck had new
      retinal emboli versus three of 29 patients (10%) who had no previous radiation
      therapy (P = 0.038). None of the other patient characteristics was associated
      with retinal embolization. In 30 (91%) of patients with an adequate acoustic
      temporal window for TCD monitoring, there was no statistically significant
      correlation between TCD data and the incidence of retinal emboli. No visual field
      defects were found. On long-term follow-up, all retinal emboli and retinal
      infarcts had resolved. Retinal embolization during CAS is not uncommon, and it
      occurs in both protected and unprotected procedures. Most retinal emboli are
      clinically silent.

PMID- 20033691
TI  - Anti N1 cross-protecting antibodies against H5N1 detected in H1N1 infected
      people.
AB  - The A(H5N1) influenza virus pandemic may be the result of avian H5N1 adapting to
      humans, leading to massive human to human transmission in a context of a lack of
      pre-existing immunity. As A(H1N1) and A(H5N1) share the same neuraminidase
      subtype, anti-N1 antibodies subsequent to H1N1 infections or vaccinations may
      confer some protection against A(H5N1). We analysed, by microneutralization
      assay, the A/Vietnam/1194/04 (H5N1) anti-N1 cross-protection acquired either
      during A/New-Caledonia/20/99 (H1N1) infection or vaccination. In cases with
      documented H1N1 infection, H5N1 cross-protection could be observed only in
      patients born between 1930 and 1950. No such protection was detected in the sera
      of vaccinated individuals.

PMID- 20033692
TI  - An application of the central limit theorem to coalescence times in the
      structured coalescent model with strong migration.
AB  - The structured coalescent describes the ancestral relationship among sampled
      genes from a geographically structured population. The aim of this article is to
      apply the central limit theorem to functionals of the migration process to study
      coalescence times and population structure. An application of the law of large
      numbers to the migration process leads to the strong migration limit for the
      distributions of coalescence times. The central limit theorem enables us to
      obtain approximate distributions of coalescence times for strong migration. We
      show that approximate distributions depend on the population structure. If
      migration is conservative and strong, we can define a kind of effective
      population size N(e)(*), with which the entire population approximately behaves
      like a panmictic population. On the other hand, the approximate distributions for
      nonconservative migration are qualitatively different from those for conservative
      migration. And the entire population behaves unlike a panmictic population even
      though migration is strong.

PMID- 20033693
TI  - Ultralow contrast medium doses at CT to diagnose pulmonary embolism in patients
      with moderate to severe renal impairment: a feasibility study.
AB  - OBJECTIVES: To analyse 80-kVp 16-MDCT in patients with clinically suspected
      pulmonary embolism (PE) and diminished renal function after a reduction in dose
      of contrast medium (CM) from 200 to 150 mg I/kg. METHODS: Fifty patients with
      suspected PE and glomerular filtration rate (GFR) less than 50 mL/min underwent
      80-kVp 16-MDCT with 150 mg I/kg. Mean density/image noise (1 standard deviation)
      was measured in a region of interest in the left pulmonary artery (LPA) and a
      lower lobe segmental artery (LLSA), and the contrast-to-noise ratio (CNR) was
      calculated. The values of LPA and LLSA were averaged. RESULTS: Median values/2.5
      97.5 percentiles were: age 84/67-96 years, weight 65/43-84 kg, GFR 36/21-45
      mL/min, CM dose 9.6/6.4-12 g of iodine, PA density 353/164-495 HU and CNR 11/4.4
      20. PE incidence was 16%, and 8% and 12% of the examinations were regarded
      suboptimal by observer 1 and 2, respectively. Density/CNR values were within
      ranges reported for common 120-kVp MDCT protocols. None of 32 patients with
      plasma-creatinine follow-up within 1 week experienced a rise of more than 44.2
      mumol/L and none of 50 patients had oliguria/anuria or dialysis. None of 40
      patients with a negative CT/no anticoagulation had thromboembolism during follow
      up. CONCLUSION: 80-kVp MDCT combined with individualised ultralow CM doses may
      provide satisfactory diagnostic quality, which should be to the benefit of
      patients at risk of contrast medium-induced nephropathy.

PMID- 20033694
TI  - Increased physical activity cosegregates with higher intake of carbohydrate and
      total calories in a subcongenic mouse strain.
AB  - C57BL/6 J (B6) and CAST/EiJ (CAST), the inbred strain derived from M. musculus
      castaneus, differ in nutrient intake behaviors, including dietary fat and
      carbohydrate consumption in a two-diet-choice paradigm. Significant quantitative
      trait loci (QTLs) for carbohydrate (Mnic1) and total energy intake (Kcal2) are
      present between these strains on chromosome (Chr) 17. Here we report the
      refinement of the Chr 17 QTL in a subcongenic strain of the B6.CAST-( D17Mit19
      D17Mit91 ) congenic mice described previously. This new subcongenic strain
      possesses CAST Chr 17 donor alleles from 4.8 to 45.4 Mb on a B6 background.
      Similar to CAST, the subcongenic mice exhibit increased carbohydrate and total
      calorie intake per body weight, while fat intake remains equivalent.
      Unexpectedly, this CAST genomic segment also confers two new physical activity
      phenotypes: 22% higher spontaneous physical activity levels and significantly
      increased voluntary wheel-running activity compared with the parental B6 strain.
      Overall, these data suggest that gene(s) involved in carbohydrate preference and
      increased physical activity are contained within the proximal region of Chr 17.
      Interval-specific microarray analysis in hypothalamus and skeletal muscle
      revealed differentially expressed genes within the subcongenic region, including
      neuropeptide W (Npw); glyoxalase I (Glo1); cytochrome P450, family 4, subfamily
      f, polypeptide 1 (Cyp4f15); phospholipase A2, group VII (Pla2g7); and
      phosphodiesterase 9a (Pde9a). This subcongenic strain offers a unique model for
      dissecting the contributions and possible interactions among genes controlling
      food intake and physical activity, key components of energy balance.

PMID- 20033695
TI  - Improved outcome in acute coronary syndrome by establishing a chest pain unit.
AB  - AIMS: Chest pain units (CPUs) have been established to optimize treatment of
      patients with acute coronary syndrome (ACS) and to early and accurately discharge
      patients with non-coronary chest pain. The aim of this analysis was to elucidate
      whether treatment of ACS patients in the CPU versus emergency department (ED) has
      prognostic implications. METHODS AND RESULTS: Patients presenting with suspected
      ACS to either the ED between August 2004 and June 2005 or the CPU between July
      2005 and May 2006 were retrospectively analyzed. Of 1,796 included patients, 483
      had the discharge diagnosis ACS. When compared to patients with exclusion of ACS
      they had more cardiovascular risk factors and higher troponin, creatinine and C
      reactive protein levels (P < 0.001) at admission. Within 1 year, 37 patients of
      the ACS group suffered an event. Treatment in the ED compared with the CPU showed
      a significant increase in hazard ratio of 2.1 (P = 0.034) for the combined
      endpoint death, myocardial infarction and stroke, remaining unchanged after
      adjusting for confounders. Event-free 1-year survival was higher in CPU patients
      for the combined endpoint (P (logrank) = 0.02). CONCLUSION: These results
      demonstrate a better 1-year prognosis for ACS patients treated in the CPU instead
      of the ED, therefore, supporting the idea to establish CPUs in Europe.

PMID- 20033697
TI  - Cross-cultural adaptation and validation of the German version of the Western
      Ontario Shoulder Instability index.
AB  - BACKGROUND: The Western Ontario shoulder instability index (WOSI) is a disease
      specific quality of life measurement tool with 21 items for patients with
      shoulder instability. Here, we report on translation and validation of the German
      version of the WOSI according to international guidelines. PATIENTS AND METHODS:
      A total of 86 patients in three groups were included in this study. In group I,
      24 patients underwent surgical stabilization of the shoulder. Preoperatively and
      at 12 months post-operatively the WOSI, Rowe score, UCLA, Constant score, and the
      SF-36 were evaluated. In group II, 25 patients were evaluated 2.6 +/- 1.2 years
      after sustaining a primary traumatic shoulder dislocation. Group III consisted of
      37 healthy men and women with normal, healthy shoulders. Evaluation of Pearson's
      correlation coefficient between WOSI and Rowe score, UCLA, SF-36 and Constant
      score and for test-retest reliability was made. Moreover, Cronbach's alpha and
      floor, and ceiling effects were analyzed. RESULTS: Internal consistency was high
      (Cronbach's alpha 0.92).Test-retest reliability (Pearson correlation coefficient)
      was excellent (r = 0.92). The construct validity showed a significant correlation
      between the WOSI and the scores investigated. There were no floor or ceiling
      effects for the German WOSI score. CONCLUSION: The German translation of the WOSI
      is a valid and reliable tool, applicable to outcome studies on patients with
      shoulder instability.

PMID- 20033696
TI  - Endoscopic plantar fasciotomy versus extracorporeal shock wave therapy for
      treatment of chronic plantar fasciitis.
AB  - BACKGROUND: Planter fasciitis is a common cause of heel pain in adults. Many
      treatment options exist. Most of patients resolve with conservative management.
      Approximately 10% of patients develop persistent and often disabling symptoms.
      PATIENTS AND METHODS: This prospective study includes 37 patients with an
      established diagnosis of chronic plantar fasciitis, aiming to compare two
      different techniques of treatment. First group includes 17 patients with a mean
      age of 42 years treated by endoscopic plantar fasciotomy (EPF); the mean follow
      up was 11 months. Second group includes 20 patients with a mean age of 45 years
      treated by extracorporeal shock Wave Therapy (ESWT); the mean follow-up was 7.6
      months. RESULTS: In the first group (EPF), using the visual analog scale the
      average post-operative pain was improved from 9.1 to 1.6. Post-operatively, 58.8%
      had no limitation of functional activities, 35.3% had minimal limitation of
      activities and 5.9% had moderate limitation of activities. Concerning patient
      satisfaction, 82.3% of patients were completely satisfied, 11.8% of patients were
      satisfied with reservation and 5.9% of patients were unsatisfied. For the second
      group (ESWT), using the visual analog scale the average post-operative pain was
      improved from 9 to 2.1. Post-operatively, 50% had no functional limitation of
      activities, 35% had minimal limitation of activities, 10% had moderate limitation
      of activities, and 5% had severe limitation of activities. Concerning patient
      satisfaction, 75% of patients were completely satisfied and 25% were satisfied
      with reservation or unsatisfied. CONCLUSION: Because of better results with
      endoscopic release versus the benefits of no complications, no immobilization,
      and early resumption of full activities with ESWT, we conclude that ESWT is a
      reasonable earlier line of treatment of chronic plantar fasciitis before EPF.

PMID- 20033698
TI  - Adductor tenotomy: its role in the management of sports-related chronic groin
      pain.
AB  - PATIENTS AND METHODS: Chronic adductor-related groin pain in athletes is
      debilitating and is often challenging to treat. Little is published on the
      surgical treatment when conservative measures fail. This single center study
      reviews the outcomes of 48 patients (68 groins) who underwent percutaneous
      adductor tenotomy for sports-related chronic groin pain. Questionnaire
      assessments were made preoperatively and at a minimum follow-up of 25 months.
      RESULTS: Mean pre-injury Tegner activity scores of 8.8 reduced to 6.1 post-injury
      and these improved to 7.7 following surgery (p < 0.001). Sixty percent of
      patients regained or bettered their pre-injury Tegner activity scores after the
      adductor surgery; however, mean post-surgical Tegner scores still remained lower
      than pre-injury scores (p < 0.001). No patient had been able to engage in their
      chosen sport at their full ability pre-operatively, and 40% had been unable to
      participate in any sporting activity. The mean return to sports was at 18.5 weeks
      postoperatively, with 54% returning to their pre-injury activity levels, and only
      8% still unable to perform athletic activities at latest follow-up. Seventy-three
      percent patients rated the outcome of their surgery as excellent or very
      satisfactory, and only three patients would not have wished to undergo the
      procedure again if symptoms recurred or developed on the opposite side. No
      patients reported their outcome as worse. A 78.1% mean improvement in function
      and an 86.5% mean improvement in pain were reported, and these two measures
      showed statistically significant correlation (p = 0.01). Groin disability scores
      improved from a mean of 11.8 to 3.9, post-operatively (p < 0.001). Bruising was
      seen in 37% of procedures, 3 patients developed a scrotal hematoma and 1 patient
      had a superficial wound infection. One patient developed recurrent symptoms
      following re-injury 26 months post-surgery, and fully recovered following a
      further adductor tenotomy. CONCLUSIONS: Adductor tenotomy provides good
      symptomatic and functional improvement in chronic adductor-related groin pain
      refractory to conservative treatment.

PMID- 20033699
TI  - CT-guided needle biopsy for musculoskeletal lesions.
AB  - INTRODUCTION: We determined the diagnostic accuracy rate of 207 cases that
      underwent CT-guided needle biopsy for musculoskeletal lesions during the past 10
      years, and describe the efficacy and indications of this method. MATERIALS AND
      METHODS: We retrospectively analyzed a consecutive series of 207 cases that
      presented to our oncology group and underwent CT-guided needle biopsy during the
      10-year period between April 1998 and March 2008. Diagnostic accuracy was
      assessed statistically by anatomical location and final diagnosis. The biopsy
      site was the spine/sacrum in 70 cases, pelvis in 53, extremities in 51,
      rib/scapula in 20, and retroperitoneum in 13. Bone lesions were detected in 176
      cases and soft tissue lesions in 31. The final diagnosis was metastatic tumor in
      63 cases, primary bone tumor in 63, primary soft tissue tumor in 23, infection in
      18, and hematopoietic malignancy in 16 and non-tumorous lesions in 24. RESULTS:
      The diagnostic accuracy rate for all cases was 90%. No serious complications were
      seen. No statistically significant difference was found by anatomical site.
      According to the final diagnosis, benign tumors/malignant tumors (p < 0.005),
      primary bone tumor (p < 0.01), and infectious conditions (p < 0.001) showed
      significantly low diagnostic accuracy rates. DISCUSSION: CT-guided needle biopsy
      is a safe method with high diagnostic accuracy for musculoskeletal lesions.
      However, in patients with a primary bone tumor, it should be indicated for the
      initial diagnosis. If a comprehensive assessment based on the imaging conflicts
      with the pathological findings, an open biopsy should be considered.

PMID- 20033700
TI  - Quality of life in patients with chronic rhinosinusitis: a validation of the
      Czech version of SNOT-22 questionnaire.

PMID- 20033701
TI  - In vivo liberation of silver ions from metallic silver surfaces.
AB  - In vivo liberation of electrically charged silver atoms/silver ions from metallic
      silver pellets, silver grids and silver threads placed in the brain, skin and
      abdominal cavity was proved by way of the histochemical technique
      autometallography (AMG). A bio-film or "dissolution membrane" inserted between
      the metallic surface and macrophages was recognized on the surface of the
      implanted silver after a short period of time. Bio-released silver ions bound in
      silver-sulphur nanocrystals were traced within the first 24 h in the "dissolution
      membrane" and the "dissolucytotic" macrophages. In animals that had survived 10
      days or more, silver nanocrystals were detected both extra- and intracellularly
      in places far away from the implant including regional lymph nodes, liver,
      kidneys and the central nervous system (CNS). The accumulated silver was always
      confined to lysosome-like organelles. Dissolucytotic silver was extracellularly
      related to collagen fibrils and fibres in connective tissue and basement
      membranes. Our study demonstrates that (1) the number of bio-released silver ions
      depends on the size of the surface of the implanted silver, (2) the spread of
      silver ions throughout the body takes place primarily not only through the
      vascular system, but also by retrograde axonal transport. It is concluded that
      implantation of silver or silver-plated devices is not recommendable.

PMID- 20033702
TI  - Palm cooling to reduce heat strain in subjects during simulated armoured vehicle
      transport.
AB  - This study examined whether palm cooling (PC) could reduce heat strain, measured
      through changes in core, mean skin, mean body temperatures, and thermal sensation
      in resting hyperthermic subjects wearing chemical protective garments. Ten male
      subjects performed three exercise bouts (6.1 km h(-1), 2-4% grade) in a hot, dry
      environment [mean (SD) air temperature 42.2 (0.5 degrees C), relative humidity
      36.5 (1%)] until core temperature reached 38.8 degrees C. Subjects then simulated
      transport in an armoured vehicle by resting in a seated position for 50 min with
      either no cooling (NC), (PC at 10 degrees C) or palm cooling with vacuum
      application around the hand (PCVAC, 10 degrees C, 7.47 kPa negative pressure).
      Core, skin, and mean body temperatures with PC and PCVAC were lower (P < 0.05)
      than NC from 15 to 50 min of cooling, and thermal sensation was lower (P < 0.05)
      from 30 to 50 min, with no differences in any variables between PC and PCVAC.
      Maximal heat extraction averaged 42 (12 W), and core temperature was reduced by
      0.38 (0.21 degrees C) after 50 min of PC. Heat extraction with PC was modest
      compared to other cooling approaches in the literature.

PMID- 20033703
TI  - Mountaineering experience decreases the net oxygen cost of climbing Mont Blanc
      (4,808 m).
AB  - The purpose of this study was to test the hypothesis that mountaineering
      experience decreases the net oxygen cost of uphill walking (OCw) on steep
      mountain trails and in ice and snow conditions. OCw was measured during an ascent
      of Mont Blanc in eight experienced alpinists and eight non-alpinists who were
      matched for sex (4 + 4) and low-altitude aerobic power (V(O)(2)(max) 50-55 ml kg(
      1) min(-1)). Subjects carried a breath-by-breath gas exchange analyzer and a GPS.
      V(O)(2)(max) at altitude was estimated from measured low-altitude V(O)(2)(max)
      using Bassett's equation to calculate fractional use of V(O)(2)(max) during the
      ascent (FV(O)(2)(max)). OCw was calculated as the difference between V(O)(2)
      while climbing minus resting V(O)(2). At all elevations, Alpinists exhibited a
      lower OCw (P < 0.01). In all subjects, OCw increased when encountering ice and
      snow conditions. FV(O)(2)(max) remained stable around 75% at all elevations
      independent of experience or sex. In conclusion, the OCw is lower in experienced
      mountaineers compared to non-experienced subjects, and increases when going from
      steep rocky mountain terrain to ice and snow conditions, independent of
      mountaineering experience or sex.

PMID- 20033704
TI  - Effect of chronic supplementation with shark liver oil on immune responses of
      exercise-trained rats.
AB  - Previous studies have reported that chronic supplementation with shark liver oil
      (SLO) improves immune response of lymphocyte, macrophage and neutrophil in animal
      models and humans. In a similar manner, exercise training also stimulates the
      immune system. However, we are not aware of any study about the association of
      exercise and SLO supplementation on immune response. Thus, our main goal was to
      investigate the effect of chronic supplementation with SLO on immune responses of
      exercise-trained rats. Male Wistar rats were divided into four groups: sedentary
      with no supplementation (SED, n = 20), sedentary with SLO supplementation
      (SEDslo, n = 20), exercised (EX, n = 17) and exercised supplemented with SLO
      (EXslo, n = 19). Rats swam for 6 weeks, 1.5 h/day, in water at 32 +/- 1 degrees
      C, with a load of 6.0% body weight attached to the thorax of rat. Animals were
      killed 48 h after the last exercise session. SLO supplementation did not change
      phagocytosis, lysosomal volume, superoxide anion and hydrogen peroxide production
      by peritoneal macrophages and blood neutrophils. Thymus and spleen lymphocyte
      proliferation were significantly higher in SEDslo, EX, and EXslo groups compared
      with SED group (P < 0.05). Gut-associated lymphocyte proliferation, on the other
      hand, was similar between the four experimental groups. Our findings show that
      SLO and EX indeed are able to increase lymphocyte proliferation, but their
      association did not induce further stimulation in the adaptive immune response
      and also did not modify innate immunity.

PMID- 20033705
TI  - Human K(ATP) channelopathies: diseases of metabolic homeostasis.
AB  - Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine
      triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP
      sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically
      active tissues throughout the body. KATP channels are metabolism-gated biosensors
      functioning as molecular rheostats that adjust membrane potential-dependent
      functions to match cellular energetic demands. Vital in the adaptive response to
      (patho)physiological stress, KATP channels serve a homeostatic role ranging from
      glucose regulation to cardioprotection. Accordingly, genetic variation in KATP
      channel subunits has been linked to the etiology of life-threatening human
      diseases. In particular, pathogenic mutations in KATP channels have been
      identified in insulin secretion disorders, namely, congenital hyperinsulinism and
      neonatal diabetes. Moreover, KATP channel defects underlie the triad of
      developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP
      channelopathies implicated in patients with mechanical and/or electrical heart
      disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and
      adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been
      associated with late-onset diabetes and as a risk factor for maladaptive cardiac
      remodeling in the community-at-large and abnormal cardiopulmonary exercise stress
      performance in patients with heart failure. The overall mutation frequency within
      KATP channel genes and the spectrum of genotype-phenotype relationships remain to
      be established, while predicting consequences of a deficit in channel function is
      becoming increasingly feasible through systems biology approaches. Thus, advances
      in molecular medicine in the emerging field of human KATP channelopathies offer
      new opportunities for targeted individualized screening, early diagnosis, and
      tailored therapy.

PMID- 20033707
TI  - Single-incision laparoscopic pyloromyotomy: initial experience.
AB  - BACKGROUND: Laparoscopic pyloromyotomy has become the standard treatment for
      hypertrophic pyloric stenosis. Single-incision laparoscopic surgery is an
      emerging operative approach that utilizes the umbilical scar to hide the surgical
      incision. OBJECTIVE: To describe our initial experience with single-incision
      laparoscopic pyloromyotomy in 15 infants. MATERIALS AND METHODS: Laparoscopic
      pyloromyotomy was performed through a single skin incision in the umbilicus,
      using a 4-mm 30 degrees endoscope and a 5-mm trocar. The 3-mm working instruments
      were inserted directly into the abdomen via separate lateral fascial stab
      incisions. All patients were prospectively evaluated. RESULTS: The procedure was
      performed in 15 infants (13 male) with mean age of 45 +/- 16 days and mean weight
      of 4.04 +/- 0.5 kg. All procedures were completed laparoscopically, and one case
      was converted to a conventional triangulated laparoscopic work configuration
      after a mucosal perforation was noted. The perforation was repaired
      laparoscopically. On average, operating time was 29.8 +/- 13.6 min, and
      postoperative length of stay was 1.5 +/- 0.8 days. All patients were discharged
      home on full feeds. Follow-up was scheduled 2-3 weeks after discharge, and no
      postoperative complications were noted in any of the patients. CONCLUSIONS:
      Single-incision laparoscopic pyloromyotomy is a safe and feasible procedure with
      good postoperative results and excellent cosmesis. The main challenge is the
      spatial orientation of the instruments and endoscope in a small working space.
      This can be overcome by a more longitudinally oriented working axis than used in
      the conventional angulated laparoscopic configuration.

PMID- 20033708
TI  - Use of flexible endoscopes for NOTES: sterilization or high-level disinfection?
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) involves the
      use of flexible endoscopes to perform intra-abdominal or intra-thoracic
      surgeries. Surgery in the operating room usually involves sterile
      instrumentation, whereas in the endoscopy suite high-level disinfection seems to
      be sufficient. Our objective was to assess the necessity for endoscope
      sterilization for clinical NOTES and to develop an endoscope processing protocol
      based on a score for the available processing options. METHODS: Score and
      processing protocol development for clinical NOTES endoscopes was based on a
      comprehensive review of the available relevant literature. Options for
      sterilization for flexible endoscopes in the Good Samaritan Hospital, Legacy
      Health in Portland, Oregon, were analyzed for patient safety, potential for
      recontamination, cost, and validation. RESULTS: Literature survey indicated that
      there is controversy surrounding the necessity for sterilization of surgical
      endoscopes. However, standard of practice seems to call for sterile
      instrumentation for surgery and it is possible to terminally sterilize flexible
      endoscopes. Within our institution, a score was created to rank the available
      sterilization options. We successfully introduced a protocol for sterilization of
      endoscopes for use in clinical NOTES procedures. The protocol involved mechanical
      cleaning and high-level disinfection per Multi-Society Guidelines, with
      subsequent terminal sterilization using a validated peracetic acid protocol.
      CONCLUSIONS: It remains controversial whether sterile instrumentation is truly
      needed for surgery. It is difficult but possible to terminally sterilize flexible
      endoscopes. We recommend sterile instrumentation for clinical NOTES until well
      designed, randomized, clinical trials are available and guidelines are published.

PMID- 20033709
TI  - Laparoscopic adrenalectomy for large unilateral pheochromocytoma: experience in a
      large academic medical center.
AB  - BACKGROUND: Laparoscopic adrenalectomy is the treatment of choice for most
      adrenal lesions. Concerns have persisted about its application to large
      pheochromocytomas due to reports of hemodynamic instability, difficult
      dissection, and tumor spillage. METHODS: Thirty patients underwent laparoscopic
      adrenalectomy for unilateral pheochromocytoma between 1998 and 2006. Outcome
      measures including operative time, blood loss, intraoperative hemodynamic
      instability, conversion rate, complications, and disease recurrence were analyzed
      based on tumor size. RESULTS: Twenty-two patients had small tumors and eight had
      large lesions. These groups did not differ in terms of operative time, blood
      loss, conversion rate, length of stay or complication rate. Intraoperative
      hemodynamic instability occurred in 56.7% of cases, but was not different between
      groups. There were no recurrences in either group. CONCLUSIONS: Laparoscopic
      adrenalectomy is a safe and effective treatment for large pheochromocytomas.
      Intraoperative hemodynamic instability remains a frequent occurrence regardless
      of tumor size. There were no cases of disease recurrence or iatrogenic
      pheochromocytosis.

PMID- 20033706
TI  - Fragile histidine triad protein: structure, function, and its association with
      tumorogenesis.
AB  - BACKGROUND: The human fragile histidine triad (FHIT) gene is a putative tumor
      suppressor gene, which is located at chromosome region 3p14.2. It was suggested
      that the loss of heterozygosity (LOH), homozygous deletions, and abnormal
      expression of the FHIT gene were involved in several types of human malignancies.
      MATERIALS AND METHODS: To determine the role of FHIT in various cancers, we have
      performed structural and functional analysis of FHIT in detail. RESULTS AND
      DISCUSSION: The protein FHIT catalyzes the Mg(2+) dependent hydrolysis of P1-5
      cent-O-adenosine-P3-5 cent-O-adenosine triphosphate, Ap3A, to AMP, and ADP. The
      reaction is thought to follow a two-step mechanism. Histidine triad proteins,
      named for a motif related to the sequence H-cent-H-cent-H-cent-cent- (cent, a
      hydrophobic amino acid), belong to superfamily of nucleotide hydrolases and
      transferases. This enzyme acts on the R-phosphate of ribonucleotides, and contain
      a approximately 30-kDa domain that is typically a homodimer of approximately 15
      kDa polypeptides with catalytic site. CONCLUSION: Here we have gathered
      information is known about biological activities of FHIT, the structural and
      biochemical bases for their functions. Our approach may provide a comparative
      framework for further investigation of FHIT.

PMID- 20033711
TI  - True single-port appendectomy: first experience with the "puppeteer technique".

PMID- 20033710
TI  - Endoscopic submucosal dissection and preoperative assessment with endoscopic
      ultrasonography for the treatment of rectal carcinoid tumors.
AB  - BACKGROUND: Rectal carcinoid tumors 10 mm in diameter or smaller located within
      the submucosal layer can be cured by local excision including endoscopic
      treatment. But complete resection of these tumors with endoscopic polypectomy is
      difficult. This study aimed to evaluate the usefulness of endoscopic submucosal
      dissection (ESD) and endoscopic ultrasonography (EUS) for the treatment of rectal
      carcinoid tumors. METHODS: In this study, 22 rectal carcinoid tumors in 21
      patients were evaluated with EUS and treated using ESD from January 2004 to
      December 2008. RESULTS: The mean size of the resected tumors was 6.1 mm (range,
      2.0-10 mm) on histopathologic evaluations. When the sizes of the tumors shown by
      EUS and histopathologic evaluation were compared, the mean values were not
      significantly different. All the tumors were located within the submucosal layer,
      and the accuracy of the preoperative depth determination with EUS was 100%
      (22/22). The mean duration of the ESD procedure was 37 min (range, 20-71 min).
      The overall rate of en bloc resection with ESD was 100% (22/22). Although
      postoperative bleeding occurred in two cases (9%), both cases were successfully
      managed by endoscopic hemostasis. No perforation or recurrence was observed
      during the mean follow-up period of 30 months (range, 7-66 months). CONCLUSIONS:
      Endoscopic submucosal dissection and preoperative assessment with EUS are
      effective for treating rectal carcinoid tumors and enabling en bloc resection.

PMID- 20033712
TI  - Comparison of endoscopic ultrasonography (EUS), positron emission tomography
      (PET), and computed tomography (CT) in the preoperative locoregional staging of
      resectable esophageal cancer.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) has been a useful method for the
      accurate staging of esophageal cancer. This study aimed to compare the diagnostic
      performance of EUS, positron emission tomography (PET), and computed tomography
      (CT) in the locoregional staging of resectable esophageal cancer. METHODS: A
      total of 109 patients with resectable esophageal cancer were prospectively
      enrolled and retrospectively reviewed for evaluation of preoperative EUS, PET,
      and CT. The sensitivity, specificity, and accuracy of tumor depth (T) staging and
      regional lymph nodal (N) staging for each test were compared with the
      postoperative histopathologic stage as the gold standard. RESULTS: The overall
      accuracy of EUS for T staging was 72%, and it was the only method for delineating
      the layers of the esophageal wall. The sensitivities for N staging were 42% for
      EUS, 49% for PET, and 35% for CT, and their specificities were, respectively, 91,
      87, and 93%. The accuracy for N staging was 66% for EUS, 68% for PET, and 63% for
      CT, and it did not differ significantly across the three tests. CONCLUSIONS:
      Preoperative EUS for the locoregional staging of esophageal cancer provides
      excellent T staging accuracy and similar accuracy for N staging compared with PET
      and CT. Especially in T staging, EUS could play an important role in the choice
      of candidates for esophageal cancer surgery.

PMID- 20033713
TI  - Application of the Hem-o-lok ligation system in laparoscopic nephrectomy.
AB  - BACKGROUND: The Hem-o-lok polymer clip has become the preferred method to control
      large vessels during operation. We explored the advantages of application of the
      Hem-o-lok ligation system in laparoscopic nephrectomy. METHODS: From January 2004
      to May 2009, 116 laparoscopic nephrectomies were performed using Hem-o-lok clips
      to control renal artery and vein, including 22 simple nephrectomies, 63 radical
      nephrectomies, and 31 nephroureterectomies. Operative time, estimated
      intraoperative blood loss, recovery time of intestinal function, postoperative
      hospital day, as well as complication rate were recorded and studied
      retrospectively. The number and cost of Hem-o-lok clips were analyzed. RESULTS:
      All 116 laparoscopic nephrectomies using Hem-o-lok clips for renal pedicle
      control were accomplished successfully without conversion to open surgery. No
      intra/postoperative vascular complications or other clip-related complications
      occurred. Laparoscopic operating time was 14-275 min (average 146.5 min).
      Estimated blood loss was 25-600 ml (average 159.2 ml). Mean recovery time of
      intestinal function was 30.4 h (range 16-72 h). Postoperative hospital stay was 4
      22 days, with an average of 7.3 days. The mean number of Hem-o-lok clip used per
      operation was 5.3 (range 4-8). CONCLUSIONS: Use of the Hem-o-lok ligation system
      to control renal pedicle is safe and reliable for laparoscopic simple/radical
      nephrectomy.

PMID- 20033714
TI  - Reactivation of adiponectin expression in obese patients after bariatric surgery.
AB  - BACKGROUND: Bariatric surgery can resolve type 2 diabetes in morbidly obese
      patients. However, the underlying mechanism is unknown. This study aimed to
      identify potential biomarkers or molecular pathways that are altered after
      bariatric surgery in diabetic and nondiabetic patients. METHODS: The study
      enrolled 17 morbidly obese patients undergoing bariatric surgery. Eight of the
      patients were diabetic, and nine were nondiabetic. In addition, a control group
      of four nonobese, nondiabetic volunteers was included. Patient blood samples were
      drawn before and after the operation. All blood samples were stabilized in
      Paxgene tubes (PreAnalytix). Total RNA was extracted and purified using the
      Paxgene Blood RNA Kit. For each sample, 100 ng of total RNA was amplified and
      labeled using the Ovation RNA Amplification System V2 with the Ovation Whole
      Blood reagent before hybridization to an Affymetrix Focus array containing more
      than 8,500 verified genes. Microarray results were analyzed with the GeneSpring
      GX 10.0 program, which uses an analysis of variance (ANOVA), and verified with
      real-time quantitative polymerase chain reaction (QPCR) using SYBR green (ABI).
      RESULTS: Microarray analysis showed that 167 genes were upregulated and 39 were
      downregulated in the obese diabetic patients. Preoperatively, adiponectin was
      downregulated 1.5-fold in diabetic versus nondiabetic patients. This was
      confirmed with quantitative PCR analysis. Preoperatively, morbidly obese patients
      showed a 3.12-fold downregulation of adiponectin expression versus the control
      group (p = 0.05). Interestingly, postoperative adiponectin levels were
      upregulated 2.79-fold (p = 0.02), which is close to the level of the normal
      control group. CONCLUSIONS: Adiponectin is dysregulated in obese patients and
      significantly dysregulated in obese diabetic patients. These findings correlate
      with the association between low levels of adiponectin and a predisposition to
      insulin resistance or diabetes. The data suggest that reactivation of adiponectin
      expression may play a part in the resolution of type 2 diabetes after bariatric
      surgery. Therefore, targeting adiponectin may help to develop alternative
      treatments for diabetes.

PMID- 20033716
TI  - Ivor Lewis esophagectomy with manual esogastric anastomosis by thoracoscopy in
      prone position and laparoscopy.
AB  - INTRODUCTION: Only a few authors have reported the technique of Ivor Lewis
      esophagectomy by minimally invasive means, and anastomosis was usually performed
      by a circular stapler. We report an Ivor Lewis esophagogastrectomy with manual
      esogastric anastomosis performed by thoracoscopy in the prone position. CASE
      REPORT: An adenocarcinoma of the distal esophagus without lymph nodes invasion
      was diagnosed in a 51-year-old man. General anesthesia and double-lumen
      endotracheal tube intubation were used. First the patient was placed in the
      supine position, and five abdominal trocars were placed. Celiac lymphadenectomy
      was performed with section of the left gastric vessels. A wide Kocher maneuver
      and pyloroplasty were performed. A wide gastric tube was performed and advanced
      through the hiatus into the right chest. Subsequently the patient was placed in
      the prone position. Three trocars (two 5-mm and one 11-mm) were placed on the
      posterior axillary line in the fifth, seventh, and ninth right intercostal space.
      The intrathoracic esophagus was dissected. Mediastinal lymphadenectomy with en
      bloc resection of the left inferior mediastinal pleura was performed. The azygos
      vein was sectioned, and the esophagus was transected by scissors 1-cm cranial to
      the azygos vein. A completely thoracoscopic manual double-layer anastomosis was
      performed by using running sutures with PDS 2/0 externally and Maxon 4/0
      internally. Finally the patient was replaced in the supine position to retrieve
      the specimen through a suprapubic incision, and the gastric tube was fixed to the
      hiatus. RESULTS: Thoracoscopy lasted 157' (anastomosis 40'), laparoscopy 160',
      and second laparoscopy 20'. Blood loss was estimated at 170 ml. The gastrograffin
      swallow on postoperative day 4 showed absence of stenosis and leak. The patient
      was discharged on postoperative day 6. CONCLUSIONS: Thoracoscopy in the prone
      position allows the surgeon to perform a thoracoscopic esogastric anastomosis
      completely handsewn without selective lung desufflation, and using only three
      trocars.

PMID- 20033715
TI  - Laparoscopic surgery for stage IV colorectal cancer.
AB  - BACKGROUND: The role of laparoscopic surgery in the management of stage IV
      colorectal cancer remains uncertain. METHODS: Sixty-five patients with stage IV
      disease from among 578 colorectal cancer patients who underwent laparoscopic
      surgery since 2001 were compared with 513 patients who had stage 0-III disease.
      The criteria for excluding stage IV patients from laparoscopic surgery were huge
      tumors, low rectal cancer, massive ascites due to peritoneal seeding, bowel
      perforation and/or obstruction, and poor general condition and/or cachexia. Data
      were analyzed by chi-square test or Student's t-test, with P < 0.05 being
      considered significant. RESULTS: The two groups of patients had similar
      demographic features. The open conversion rate was 4.6% (3/65 patients) in the
      stage IV group and 2.7% (14/513 patients) in the stage 0-III group, and the
      difference between the groups was not significant. In the stage IV group, depth
      of tumor invasion and tumor diameter were both significantly greater than in the
      stage 0-III group. However, operating time and blood loss were similar in the two
      groups (stage IV: 189.0 min and 95.0 g; stage 0-III: 182.5 min and 60.0 g),
      although blood loss was significantly greater in the stage IV group when patients
      undergoing rectal surgery were compared. The incidence of postoperative
      complications and the postoperative course of the two groups were similar.
      CONCLUSIONS: Despite their larger and more invasive tumors, the short-term
      outcome of laparoscopic surgery in patients with stage IV colorectal cancer was
      similar to that for stage 0-III patients. This result indicates that laparoscopic
      surgery can be successfully performed in selected stage IV colorectal cancer
      patients.

PMID- 20033718
TI  - Fixation of mesh to the peritoneum using a fibrin glue: investigations with a
      biomechanical model and an experimental laparoscopic porcine model.

PMID- 20033719
TI  - Povidone-iodine surgical scrub solution prevents fogging of the scope's lens
      during laparoscopic surgery.
AB  - Easy cleaning of the scope's lens in a syringe to prevent condensation during
      laparoscopic surgery is a simple and good way to use antifog solution more easily
      during laparoscopic surgery. This report explains a more inexpensive way to
      overcome condensation during laparoscopic surgery. Rubbing povidone-iodine
      surgical scrub solution on the scope's lens prevents its fogging during
      laparoscopic surgery.

PMID- 20033720
TI  - The effect of defined auditory conditions versus mental loading on the
      laparoscopic motor skill performance of experts.
AB  - BACKGROUND: Music and noise are frequent occurrences in the operating room. To
      date, the effects of these auditory conditions on the performance of laparoscopic
      surgery experts have not been evaluated. METHODS: Eight internationally
      recognized experts were recruited for a crossover study. The experts were
      randomized to perform three simple tasks on a laparoscopic simulator, SurgicalSIM
      VR. The tasks were equal in difficulty and performed under the following
      conditions: silence, dichaotic music (auditory stress), classical music (auditory
      relaxation), and mental loading (mental arithmetic tasks). Permutations of the
      conditions were created to account for a learning effect. The tasks were
      performed twice to test for memory consolidation and to accommodate baseline
      variability. Time until task completion and task accuracy via instrument tip
      trajectory (path of the tip through space) were recorded. Performance was
      correlated with responses on the Brief Musical Experience Questionnaire (MEQ).
      RESULTS: The study demonstrated that dichaotic music has a negative impact on
      time until task completion but not on task accuracy. In addition, memory
      consolidation of accuracy is negatively influenced. Classical music has a
      variable effect on experts' time until task completion, yet all the experts
      performed the tasks more accurately. Classical music had no effect on recall of a
      procedure. Mental loading increased time until completion, but did not affect
      accuracy or recall. The experience of music varied among experts and influenced
      how each of the conditions affected their performance. CONCLUSION: The study
      demonstrated that, contrary to common belief, proficiency in surgery does not
      protect against stressful auditory influences or the influence of mental
      preoccupation. Interestingly, relaxing auditory influences such as classical
      music can even have a positive impact on the accuracy of experts. Previous
      musical experience could help to identify surgeons whose performance may be
      specifically affected by music or noise.

PMID- 20033721
TI  - Adaptation to a dynamic visual perspective in laparoscopy through training in the
      cutting task.
AB  - BACKGROUND: Laparoscopic surgery demands of surgeons special skills acquired only
      through practice. Laparoscopic training systems traditionally have an optical
      system that, once positioned, remains fixed and cannot refresh the perspective
      unless the task is interrupted and the camera repositioned. During a surgery, the
      visual perspective changes constantly to relocate the surgical target. This
      difference is a limitation for any novice surgeon. This report proposes the use
      of a mechatronic system that allows the trainee to handle optics dynamically
      during training in the cutting task and thereby adapt to dynamic relocation of
      the surgical target. METHODS: The study was conducted in two phases. The first
      phase involved using fixed optics to cut a circle drawn on a piece of cloth. The
      second phase involved the same cutting task but with the visual perspective
      changed dynamically by the user via a mechatronic assistant. RESULTS: The data
      show that by adapting to dynamic optics, medical trainees can quickly and easily
      handle and locate the task with real-time changes in visual perspective and can
      also improve task quality. A significant statistical difference was found between
      the two methods performed (p < 0.0025). Variance analysis also was applied to the
      mean values of the scores achieved by both groups (p < 0.0001). CONCLUSIONS: A
      new laparoscopic training method has been developed. It applies real-time dynamic
      optics that trainees assist by means of a mechatronic device harnessed to their
      body. This new training tool allows resident trainees to adapt quickly to the
      work environment of dynamic optics and thus enter the surgical scenario more
      rapidly and confidently after mastering the visual-spatial aspect of the
      laparoscopic approach.

PMID- 20033722
TI  - Is the laparoscopic approach to colectomy safe for the morbidly obese?
AB  - BACKGROUND: The feasibility and safety of laparoscopic colectomy (LC) for
      morbidly obese patients has not been reported previously. This study aimed to
      assess the clinical outcomes of patients with a body mass index (BMI) of 40
      kg/m(3) or more who undergo laparoscopic colorectal surgery. METHODS:
      Prospectively accrued data for patients with a BMI of 40 kg/m(3) or more (group
      A) who undergo LC were compared with those for patients with BMI lower than 30
      kg/m(3) (group B) matched for year of surgery, indication, operating surgeon, and
      type of procedure. RESULTS: Each group had 36 patients. The group A patients were
      significantly younger (54 vs. 61 years; P = 0.04), had higher American Society of
      Anesthesiology (ASA) scores (P = 0.001), and had diabetes mellitus (P = 0.04).
      The indications for surgery and the operations performed were similar. The two
      groups had similar operating times (177.9 vs. 136.4 min; P = 0.12), estimated
      blood losses (222.3 vs. 157 ml; P = 0.1), median lengths of hospital stay (LOS)
      (4.5 vs. 4 days; P = 0.2), and returns of bowel function (4.2 vs. 3.9 days; P =
      0.45). Group A had significantly longer incisions (6.9 vs. 5 cm; P = 0.02).
      Conversions (5 vs. 3 patients; P = 0.7), readmissions (12 vs. 6 patients; P =
      0.46), reoperations (5 vs. 3 patients; P = 0.17), wound infections (7 vs. 2
      patients; P = 0.14), anastomotic leaks (3 vs. 2 patients; P = 0.7), and abdominal
      abscesses (3 vs. 2 patients; P = 0.7) were more predominant in group A, although
      the differences did not reach statistical significance. CONCLUSIONS: Laparoscopic
      colectomy is feasible for morbidly obese patients and results in recovery of
      intestinal function and LOS equivalent to that for nonobese patients. As
      expected, morbidity and conversion rates are higher for morbidly obese patients
      undergoing LC than for nonobese patients.

PMID- 20033723
TI  - "Chopstick" surgery: a novel technique improves surgeon performance and
      eliminates arm collision in robotic single-incision laparoscopic surgery.
AB  - INTRODUCTION: Single-incision laparoscopic surgery (SILS) is limited by the
      coaxial arrangement of the instruments. A surgical robot with wristed instruments
      could overcome this limitation, but the arms often collide when working
      coaxially. This study tests a new technique of "chopstick" surgery to enable use
      of the robotic arms through a single incision without collision. METHODS:
      Experiments were conducted utilizing the da Vinci S robot (Intuitive Surgical,
      Inc., Sunnyvale, CA) in a Fundamentals of Laparoscopic Surgery (FLS) box trainer
      with three laparoscopic ports (1 x 12 mm, 2 x 5 mm) introduced through a single
      "incision." Pilot work determined the optimal setup for SILS to be a triangular
      port arrangement with 2-cm trocar distance and remote center at the abdominal
      wall. Using this setup, five experienced robotic surgeons performed three FLS
      tasks utilizing either a standard robotic arm setup or the chopstick technique.
      The chopstick arrangement crosses the instruments at the abdominal wall so that
      the right instrument is on the left side of the target and the left instrument on
      the right. This results in separation of the robotic arms outside the box. To
      correct for the change in handedness, the robotic console is instructed to drive
      the "left" instrument with the right-hand effector and the "right" instrument
      with the left. Performances were compared while measuring time, errors, number of
      clutching maneuvers, and degree of instrument collision (Likert scale 1-4).
      RESULTS: Compared with the standard setup, the chopstick configuration increased
      surgeon dexterity and global performance through significantly improved
      performance times, eliminating instrument collision, and decreasing number of
      camera manipulations, clutching maneuvers, and errors during all tasks.
      CONCLUSION: Chopstick surgery significantly enhances the functionality of the
      surgical robot when working through a small single incision. This technique will
      enable surgeons to utilize the robot for SILS and possibly for intraluminal or
      transluminal surgery.

PMID- 20033724
TI  - Tensile strength and adhesion formation of mesh fixation systems used in
      laparoscopic incisional hernia repair.
AB  - BACKGROUND: Mesh tearoff from the tissue is the most common reason for hernia
      recurrence after hernia surgery involving the use of a synthetic mesh. Various
      fixation systems were critically compared in terms of their retention strength
      and the formation of adhesions. METHODS: In a prospective study with 25 Sprague
      Dawley rats, two pieces of Parietex composite meshes measuring 2 x 3 cm were
      fixed intraperitoneally in a paramedian location. The randomized mesh fixation
      groups included transfascial fixed suture, ProTack, AbsorbaTack, and I-Clip. Of
      the 25 rats, 12 were killed and analyzed 1 week after implantation, with the
      remaining 13 rats killed and analyzed after 2 months. Adhesions observed at the
      time of mesh removal were measured according to an adhesion scoring system, and
      the fixation strengths of the individual fixation systems were tested.
      Additionally, the foreign body reaction to the mesh and fixation systems was
      measured as well as their potential degradation. RESULTS: After 1 week, the
      retention strength of transfascial fixed suture was significantly higher (8.7
      N/cm(2)) than that of ProTack (5.6 N/cm(2)) or AbsorbaTack (5.7 N/cm(2)). After 2
      months, the retention strength had increased to 13.2 N/cm(2) in the transfascial
      fixed suture group, which was significantly higher than in the ProTack (9.7
      N/cm(2)) or AbsorbaTack (8.7 N/cm(2)) groups. In contrast, the mesh could be
      fixed with the I-Clip only in 56% of the cases, and then achieved rather poor
      retention strength. Adhesion was significantly greater in the ProTack group than
      in any of the other groups (p < 0.001). At 2 months, scanning electron microscopy
      showed only marginal degradation of the absorbable elements. CONCLUSIONS: Suture
      fixation led to satisfactory attachment of the prosthesis. Additional widespread
      anchorage of the mesh was achieved with ProTack or AbsorbaTack. The feasibility
      and retention strength of the I-Clip were poor.

PMID- 20033725
TI  - Laparoscopic correction of perforated peptic ulcer: first choice? A review of
      literature.
AB  - BACKGROUND: Perforated peptic ulcer (PPU), despite antiulcer medication and
      Helicobacter eradication, is still the most common indication for emergency
      gastric surgery associated with high morbidity and mortality. Outcome might be
      improved by performing this procedure laparoscopically, but there is no consensus
      on whether the benefits of laparoscopic closure of perforated peptic ulcer
      outweigh the disadvantages such as prolonged surgery time and greater expense.
      METHODS: An electronic literature search was done by using PubMed and EMBASE
      databases. Relevant papers written between January 1989 and May 2009 were
      selected and scored according to Effective Public Health Practice Project
      guidelines. RESULTS: Data were extracted from 56 papers, as summarized in Tables
      1-7. The overall conversion rate for laparoscopic correction of perforated peptic
      ulcer was 12.4%, with main reason for conversion being the diameter of
      perforation. Patients presenting with PPU were predominantly men (79%), with an
      average age of 48 years. One-third had a history of peptic ulcer disease, and one
      fifth took nonsteroidal anti-inflammatory drugs (NSAIDs). Only 7% presented with
      shock at admission. There seems to be no consensus on the perfect setup for
      surgery and/or operating technique. In the laparoscopic groups, operating time
      was significant longer and incidence of recurrent leakage at the repair site was
      higher. Nonetheless there was significant less postoperative pain, lower
      morbidity, less mortality, and shorter hospital stay. CONCLUSION: There are good
      arguments that laparoscopic correction of PPU should be first treatment of
      choice. A Boey score of 3, age over 70 years, and symptoms persisting longer than
      24 h are associated with higher morbidity and mortality and should be considered
      contraindications for laparoscopic intervention.

PMID- 20033726
TI  - Mesh-fixation method and pain and quality of life after laparoscopic ventral or
      incisional hernia repair: a randomized trial of three fixation techniques.
AB  - BACKGROUND: Persistent, activity-limiting pain after laparoscopic ventral or
      incisional hernia repair (LVIHR) appears to be related to fixation of the
      implanted mesh. A randomized study comparing commonly used fixation techniques
      with respect to postoperative pain and quality of life has not previously been
      reported. METHODS: A total of 199 patients undergoing non-urgent LVIHR in our
      unit between August 2005 and July 2008 were randomly assigned to one of three
      mesh-fixation groups: absorbable sutures (AS) with tacks; double crown (DC),
      which involved two circles of tacks and no sutures; and nonabsorbable sutures
      (NS) with tacks. All operations were performed by one of two experienced
      surgeons, who used a standardized technique and the same type of mesh and mesh
      fixation materials. The severity of the patients' pain was assessed
      preoperatively and at 2 weeks, 6 weeks and 3 months postoperatively by using a
      visual analogue scale (VAS). Quality of life (QoL) was evaluated by administering
      a standard health survey before and 3 months after surgery. Results in the three
      groups were compared. RESULTS: The AS, DC, and NS mesh-fixation groups had
      similar patient demographic, hernia and operative characteristics. There were no
      significant differences among the groups in VAS scores at any assessment time or
      in the change in VAS score from preoperative to postoperative evaluations. The
      QoL survey data showed a significant difference among groups for only two of the
      eight health areas analyzed. CONCLUSION: In this trial, the three mesh-fixation
      methods were associated with similar postoperative pain and QoL findings. These
      results suggest that none of the techniques can be considered to have a pain
      reduction advantage over the others. Development of new methods for securing the
      mesh may be required to decrease the rate or severity of pain after LVIHR.

PMID- 20033727
TI  - Impact of laparoscopic anterior 270 degrees fundoplication on the quality of life
      and symptoms profile of neurodevelopmentally delayed versus neurologically
      unimpaired children and their parents.
AB  - BACKGROUND: This prospective study investigated the therapy-induced changes in
      the quality of life (QoL) experienced by neurologically healthy and
      neurodevelopmentally delayed children and their parents after laparoscopic
      anterior 270 degrees fundoplication (LAF). METHODS: In this study, 40 patients
      (21 impaired) with a mean age of 7.8 years underwent LAF for gastroesophageal
      reflux disease (GERD) and were evaluated before surgery and then 3 and 6 months
      afterward using the Gastrointestinal Quality-of-Life Index (GIQLI) supplemented
      by conventional symptom markers. RESULTS: Growth, proton pump inhibitor use, and
      frequency of supraesophageal/respiratory symptoms improved significantly (p <
      0.001) as did feeding parameters (p < 0.05). The global GIQLI score improved by
      49 +/- 21% (p < 0.001). The greatest improvement occurred in the symptoms domain
      (p < 0.001). However, positive alterations also were found in the dimensions of
      emotions (58%), social functions (37%) and physical functions (27%) (p < 0.001).
      Comparison of the overall benefit did not show any differences between the
      subgroups of neurologically fit and impaired children. However, for the child
      centered symptoms domain, the benefit increased stepwise with the degree of
      impairment. This was counterbalanced by an inverse relationship for the parent
      centered emotions domain (p < 0.05). CONCLUSIONS: Besides the known improvement
      in symptoms, LAF achieves a significant improvement in QoL for children and their
      parents. There is no overall difference in the benefit experienced by
      neurologically impaired and healthy children.

PMID- 20033729
TI  - Directed submucosal tunneling permits in-line endoscope positioning for
      transgastric natural orifice translumenal endoscopic surgery (NOTES).
AB  - BACKGROUND: Submucosal dissection is demonstrated to be a technically feasible,
      safe means of obtaining peroral transgastric peritoneal access for natural
      orifice translumenal endoscopic surgery (NOTES). The authors hypothesized that
      their previously described self-approximating translumenal access technique
      (STAT) could be used to create directed gastric submucosal tunnels permitting in
      line endoscope positioning with predetermined abdominal locations that might
      otherwise be difficult to access. METHODS: In this study, 14 domestic farm swine
      underwent peroral transgastric peritoneoscopy. Under direct endoscopic
      visualization, a submucosal tunnel was created by dissecting between the mucosal
      and muscular layers of the stomach. Each tunnel was created with one of four
      intraabdominal locations (right upper quadrant, left upper quadrant, lesser sac,
      and pelvis) as the final target for in-line endoscope positioning. Once
      peritoneal access had been achieved, in-line positioning was assessed and
      peritoneoscopy was performed. The submucosal tunnels were closed with
      endoscopically placed clips. The animals were killed 2 weeks after the procedure,
      and necropsy was performed. RESULTS: Submucosal tunnels were successfully
      directed at predetermined intraabdominal targets in 12 of the 14 animals. The
      mean dissection time required to create the tunnel was 51 +/- 32 min. All the
      transgastric tunnels were successfully closed with endoscopically placed clips
      (mean, 3.2 +/- 1.1), and at necropsy showed no evidence of gastrotomy leak in any
      of the animals. One animal experienced a duodenal perforation unrelated to the
      transgastric tunneling and was killed on postoperative day 2. The remaining
      animals recovered and gained weight (mean, 5.5 +/- 1.2 kg) in the 2-week survival
      period. CONCLUSIONS: Directed submucosal dissection is technically feasible in a
      porcine model and permits in-line endoscope positioning with predetermined
      abdominal target locations. The STAT approach provides safe peritoneal access,
      allows for a simple reliable endoclip closure, and has an excellent short-term
      survival rate. This method of achieving transgastric access may be an enabling
      technique for future NOTES procedures.

PMID- 20033728
TI  - Laparoscopic versus open colectomy for patients with American Society of
      Anesthesiology (ASA) classifications 3 and 4: the minimally invasive approach is
      associated with significantly quicker recovery and reduced costs.
AB  - BACKGROUND: Conceivably, the benefits of earlier recovery associated with a
      minimally invasive technique used in laparoscopic colectomy (LC) may be amplified
      for patients with comorbid disease. The dearth of evidence supporting the safety
      of laparoscopy for these patients led to a comparison of outcomes between LC and
      open colectomy (OC) for patients with American Society of Anesthesiology (ASA)
      classifications 3 and 4. METHODS: Data for all ASA 3 and 4 patients who underwent
      elective LC were reviewed from a prospectively maintained laparoscopic database.
      The patients who underwent LC were matched with OC patients by age, gender,
      diagnosis, year, and type of surgery. Estimated blood loss, operation time, time
      to return of bowel function, length of hospital stay, readmission rate, and 30
      day complication and mortality rates were compared using chi-square, Fisher's
      exact, and Wilcoxon tests as appropriate. A p value <0.05 was considered
      statistically significant. RESULTS: In this study, 231 LCs were matched with 231
      OCs. The median age of the patients was 68 years, and 234 (51%) of the patients
      were male. There were 44 (19%) conversions from LC to OC. More patients in the OC
      group had undergone previous major laparotomy (5 vs. 15%; p < 0.001). Estimated
      blood loss, return of bowel function, length of hospital stay, and total direct
      costs were decreased in the LC group. Wound infection was significantly greater
      with OC (p = 0.02). When patients with previous major laparotomy were excluded,
      the two groups had similar overall morbidity. The other benefits of LC, however,
      persisted. CONCLUSION: The findings show that LC is a safe option for patients
      with a high ASA classification. The LC approach is associated with faster
      postoperative recovery, lower morbidity rates, and lower hospital costs than the
      OC approach.

PMID- 20033730
TI  - Transoral thyroid and parathyroid surgery.
AB  - BACKGROUND: Translumenal endoscopic interventions via so-called natural orifices
      are gaining increasing interest because they allow surgical treatment without any
      incision of the skin. Moreover, minimally invasive procedures have found their
      way into thyroid and parathyroid surgery. Our goal was to develop a new access
      for thyroid and parathyroid resection via an entirely transoral approach.
      METHODS: We managed to find an entirely transoral sublingual access to the
      thyroid region in pigs and human cadavers. Using a modified rigid rectoscope
      (oraloscope) hemithyroidectomies as well as resection of parathyroid glands were
      performed via this new approach. Preparation and resection was performed using
      conventional laparoscopic instruments. In living pigs, integrity of the recurrent
      laryngeal nerve after resection could be documented by neuromonitoring. An
      absorbable suture was used to seal the mucosal incision. RESULTS: First,
      hemithyroidectomy was performed via the transoral access in 10 porcine cadavers,
      then in 10 living and orally intubated pigs, and finally in five human corpses.
      In humans, resection of parathyroid glands also was performed. We gained access
      to the thyroid region by blunt dissection of the layer behind the hyoid bone and
      the strap muscles of the neck. We did not observe any complication during the
      insertion, resection, and removal part of the new procedure. CONCLUSIONS:
      Entirely transoral thyroid and parathyroid surgery via sublingual access seems to
      be feasible. However, further investigations are needed to evaluate the safety of
      the new technique, especially potential and clinically relevant contamination of
      the access route has to be excluded.

PMID- 20033731
TI  - Overcoming technical challenges with robotic surgery in gynecologic oncology.
AB  - BACKGROUND: The majority of data published on robotic surgery in gynecologic
      oncology has focused on patient outcomes and surgical data. We have found that
      technical challenges due to the complexity of the robotic technology create a
      separate set of issues, adding time and difficulty to the actual surgical
      procedure. This study focuses on these technical problems and identifies pitfalls
      and potential solutions in robotics. METHODS: All patients who underwent robotic
      surgery for gynecologic oncology indications from August 2006 through July 2008
      were eligible for inclusion in the study. Data collected prospectively included
      demographics, surgical and clinicopathologic data, and technical problems with
      the robotic equipment. RESULTS: One hundred thirty-seven patients underwent
      robotic surgery during the study period. A total of 11 cases (8.02%) were
      associated with problems with robotic technology: 2/11 (18.2%) involved
      malfunction of robotic arms, 2/11 (18.2%) involved light or camera cords, and the
      remainder included a variety of problems, including malfunction of Maylard
      bipolar instrument [1/11 (9.1%)], power failure requiring reboot of robot [1/11
      (9.1%)], port problems [2/11 (18.2%)], and 3/1 (27.3%) had miscellaneous
      problems. An estimated average of 25 min was added to each of these 11 cases in
      order to solve robot-related technological problems. No cases required conversion
      to laparotomy. All problems were solved by the robotic surgeon with the
      assistance of robotic surgery staff. CONCLUSIONS: Surgeons performing robotic
      surgery must become familiar with troubleshooting robotic technology. Several
      issues related to technical problems may arise, delaying progression of the case,
      and potential solutions were identified. As this technology is implemented,
      robotic surgeons must be trained to solve problems related to the robotic
      technology and associated equipment. Failure to do so may add time and technical
      difficulty to robotic cases.

PMID- 20033732
TI  - A population-based analysis of emergent vs. elective hospital admissions for an
      intrathoracic stomach.
AB  - BACKGROUND: Large-scale, population-based analyses of the demographics,
      management, and healthcare resource utilization of patients with an intrathoracic
      stomach are largely unknown, an issue which has become more important with the
      aging of the population. Our objective was to understand the magnitude of the
      problem and to assess clinical outcomes and hospital costs in elective and
      emergent admissions of patients with an intrathoracic stomach in a large
      population-based study. METHODS: The New York Statewide Planning and Research
      Cooperative System (SPARCS) administrative database was queried for primary ICD-9
      CM codes 553.3 and 552.3 in patients 18 years or older; 4858 hospital admissions
      were identified over a 5-year period (2002-2006). Database variables included
      age, gender, race, type of admission, operative intervention, in-hospital
      mortality, length of stay, and cost. RESULTS: Approximately 1000 patients are
      admitted to the hospital each year with primary diagnosis of intrathoracic
      stomach, an estimated 52 per 1 million of the population in New York State. Over
      half of those (53%) were emergent admissions. Interestingly, the majority of
      emergent admissions (66%) were discharged before any surgical intervention.
      Patients admitted emergently were older (68.0 vs. 62.1 years, p < 0.0001) and
      more likely African-American (12% vs. 6%, p < 0.0001). Compared to elective
      admissions, emergent admissions had higher mortality (2.7% vs. 1.2%, p < 0.001),
      longer length of stay (LOS) (7.3 vs. 4.9 days, p < 0.0001), and higher cost
      ($28,484 vs. $24,069, p < 0.001). Among patients who underwent surgery, emergent
      admissions had higher mortality (5.1% vs. 1.1%, p < 0.0001), greater LOS (13.1
      vs. 4.9 days, p < 0.0001), and higher costs ($55,460 vs. $24,760, p < 0.0001).
      Multivariate regression analysis demonstrated age, emergent presentation, and
      operative admission as independent predictors for hospital mortality, LOS, and
      cost (p < 0.0001). CONCLUSIONS: Strikingly, more than half of admissions for
      intrathoracic stomach were emergent. Emergent admissions had higher mortality,
      longer LOS, and higher cost than elective admissions. These data support
      consideration of early elective repair.

PMID- 20033733
TI  - Gaze disruptions experienced by the laparoscopic operating surgeon.
AB  - BACKGROUND: Disruptions to surgical workflow have been correlated with an
      increase in surgical errors and suboptimal outcomes in patient safety measures.
      Yet, our ability to quantify such threats to patient safety remains inadequate.
      Data are needed to gauge how the laparoscopic operating room work environment,
      where the visual and motor axes are no longer aligned, contributes to such
      disruptions. We used time motion analysis techniques to measure surgeon attention
      during laparoscopic cholecystectomy in order to characterize disruptive events
      imposed by the work environment of the OR. In this investigation we identify
      attention disruptions as they occur in terms of the operating surgeon's gaze. We
      then quantify such disruptions and also seek to establish what occasioned them.
      METHODS: Ten laparoscopic cholecystectomy procedures were recorded with both
      intra- and extracorporeal cameras. The views were synchronized to produce a video
      that was subsequently analyzed by a single independent observer. Each time the
      surgeon's gaze was diverted from the operation's video display, the event was
      recorded via time-stamp. The reason for looking away (e.g., instrument exchange),
      when discernable, was also recorded and categorized. Disruptions were then
      reviewed and analyzed by an interdisciplinary team of surgeons and human factors
      experts. RESULTS: Gaze disruptions were classified into one of four causal
      categories: instrument exchange, extracorporeal work, equipment troubleshooting,
      and communication. On average, 40 breaks occurred in operating surgeon attention
      per 15 min of operating time. The most frequent reasons for these disruptions
      involved instrument exchange (38%) and downward gaze for extracorporeal work
      (28%). CONCLUSIONS: This study of laparoscopic cholecystectomy performance
      reveals a high gaze disruption rate in the current operating room work
      environment. Improvements aimed at reducing such disruptions-and thus potentially
      surgical error-should center on better instrument design and realigning the axis
      between surgeon's eye and visual display.

PMID- 20033734
TI  - Using external magnet guidance and endoscopically placed magnets to create suture
      free gastro-enteral anastomoses.
AB  - BACKGROUND: To facilitate endolumenal and natural orifice procedures, this study
      evaluated a novel technique using external and endoscopically placed magnets to
      create suture-free gastroenteral anastomoses. METHODS: Seven anesthetized adult
      swine underwent endoscopic placement of magnets into the small bowel and stomach.
      Using external magnets, the endoscopically placed internal magnets were brought
      into opposition under endoscopic view. After 1-2 weeks, the pigs were killed and
      analyzed. At laparotomy and under sterile conditions, peritoneal cultures were
      obtained. The anastomoses were evaluated endoscopically and tested using an air
      insufflation test. Finally, the anastomoses were resected and evaluated
      microscopically. RESULTS: The average operative time for endoscopic placement of
      the magnets was 34.3 +/- 14.8 min. Successful placement and creation of
      anastomoses occurred in six of the pigs. One pig did not form an anastomosis
      because the magnets were too large to pass through the pylorus at the time of
      attempted magnet placement. Six swine experienced uncomplicated postoperative
      courses. One pig's postoperative course involved constipation for several days,
      requiring additional fluids and fiber supplementation. The findings at endoscopy
      showed that the magnets were adhered to the anastomosis, which were easily freed,
      or within the stomach. The air insufflation test results were negative for all
      the pigs. At laparotomy, there was no evidence of infection, abscess, or leak,
      but two peritoneal culture results were positive with scant growth of
      Staphylococcus aureus and coagulase-negative staphylococcus, presumably
      contaminants. Microscopically, the anastomoses illustrated granulation and
      fibrous connective tissue without evidence of infection or leak. CONCLUSION:
      Endoscopically placed magnets with external magnet guidance is a feasible and
      novel approach to creating patent gastroenteral anastomoses without abdominal
      incisions or sutures.

PMID- 20033735
TI  - Etiology and treatment of growth retardation in children with chronic kidney
      disease and end-stage renal disease: a historical perspective.
AB  - Dramatic changes have occurred in our understanding of the etiology of the growth
      retardation associated with chronic kidney disease (CKD) and end-stage renal
      disease (ESRD) during the past 50 years. Significant interest has been focused on
      preventing and/or correcting the growth retardation because of the emergence of
      the dual therapeutic modalities of dialysis and renal transplantation to prolong
      the lives of infants, children, and adolescents afflicted with CKD and ESRD.
      These efforts have resulted in a significant improvement in the height Z-score
      over the past two decades of children with CKD and ESRD. This has had a salutary
      impact on the final adult height of such children which should hopefully lead to
      an enhanced quality of life in the future. This report addresses the progress
      that has been made in the management of growth retardation in the pediatric
      population with CKD and ESRD.

PMID- 20033736
TI  - Indoor and outdoor atmospheric fungal spores in the Sao Paulo metropolitan area
      (Brazil): species and numeric concentrations.
AB  - The aim of this study was to estimate the indoor and outdoor concentrations of
      fungal spores in the Metropolitan Area of Sao Paulo (MASP), collected at
      different sites in winter/spring and summer seasons. The techniques adopted
      included cultivation (samples collected with impactors) and microscopic
      enumeration (samples collected with impingers). The overall results showed total
      concentrations of fungal spores as high as 36,000 per cubic meter, with a large
      proportion of non culturable spores (around 91% of the total). Penicillium sp.
      and Aspergillus sp. were the dominant species both indoors and outdoors, in all
      seasons tested, occurring in more than 30% of homes at very high concentrations
      of culturable airborne fungi [colony forming units(CFU) m(-3)]. There was no
      significant difference between indoor and outdoor concentrations. The total
      fungal spore concentration found in winter was 19% higher than that in summer.
      Heat and humidity were the main factors affecting fungal growth; however, a non
      linear response to these factors was found. Thus, temperatures below 16 degrees C
      and above 25 degrees C caused a reduction in the concentration (CFU m(-3)) of
      airborne fungi, which fits with MASP climatalogy. The same pattern was observed
      for humidity, although not as clearly as with temperature given the usual high
      relative humidity (above 70%) in the study area. These results are relevant for
      public health interventions that aim to reduce respiratory morbidity among
      susceptible populations.

PMID- 20033737
TI  - Can NPK fertilizers enhance seedling growth and mycorrhizal status of Tuber
      melanosporum-inoculated Quercus ilex seedlings?
AB  - Although successful cultivation of the black truffle (Tuber melanosporum) has
      inspired the establishment of widespread truffle orchards in agricultural lands
      throughout the world, there are many unknowns involved in proper management of
      orchards during the 6-10 years prior to truffle production, and there are
      conflicting results reported for fertilizer treatments. Here, we systematically
      evaluate the combined effects of nitrogen, phosphorous, and potassium with
      different doses of each element, applied to either foliage or roots, on plant
      growth parameters and the mycorrhizal status of outplanted 3-year-old seedlings
      in five experimental Quercus ilex-T. melanosporum orchards. Fertilization did not
      significantly improve seedling aboveground growth, but the plants treated with
      the fertilizer 12-7-7 applied to the roots (HNr) displayed longer field-developed
      roots. Only the fertilizer with the highest dose of K (10-6-28) applied to the
      foliage (HKf) increased the probability of fine root tip colonization by T.
      melanosporum in field-developed roots. However, the plants treated with the same
      fertilizer applied to the soil (HKr) presented the highest probability for
      colonization by other competing mycorrhizal soil fungi. Potassium seems to have
      an important role in mycorrhizal development in these soils. Apart from T.
      melanosporum, we found 14 ectomycorrhizal morphotypes, from which seven were
      identified to species level, three to genus, two to family, and two remained
      unidentified by their morphological characteristics and DNA analyses.

PMID- 20033738
TI  - Education program of EuroSpine/The Spine Society of Europe.

PMID- 20033739
TI  - Changes in paraspinal muscles and their association with low back pain and spinal
      degeneration: CT study.
AB  - The objectives of the study were to evaluate the association between lumbar
      paraspinal muscle density, evaluated on computed tomography (CT) and age, sex and
      BMI; and to evaluate the association of those changes with low back pain (LBP)
      and spinal degeneration features in a community-based sample. This study was an
      ancillary project to the Framingham Study. A sample of 3,529 participants aged 40
      80 years had a CT scan performed to assess aortic calcification. 187 individuals
      were randomly enrolled in this study. LBP in the last 12 months was evaluated
      using self-report questionnaire. Density (in Hounsfield units) of multifidus and
      erector spinae was evaluated on CT. The prevalence of intervertebral disc
      narrowing, facet joint osteoarthritis (FJOA), spondylolysis, spondylolisthesis
      and spinal stenosis were also evaluated. We used linear regression models to
      examine the association of paraspinal muscles density with age, sex, BMI, LBP,
      and spinal degeneration features. The results show that in our study, men have
      higher density of paraspinal muscles than women, younger individuals have higher
      density than older ones and individuals with lower weight have higher muscle
      density than overweight. No differences between individuals with and without LBP
      were found. Significant association was found between L4 multifidus/erector
      spinae density and FJOA at L4-L5; between multifidus at L4 and spondylolisthesis
      at L4-5; and between erector spinae at L4 and L5 with disc narrowing at L4-5 and
      L5-S1, respectively. We conclude that the paraspinal muscle density decreases
      with age, and increases BMI. It is associated with at some levels FJOA,
      spondylolisthesis and disc narrowing at the same level, but not associated with
      occurrence of LBP.

PMID- 20033740
TI  - A morphological adaptation of the thoracic and lumbar vertebrae to lumbar
      hyperlordosis in young and adult females.
AB  - The lumbar shape in females is thought to be unique, compensating for lumbar
      hyperlordosis. Yet, the morphological adaptation of various vertebral parameters
      in the thoracic and lumbar spine to this unique posture in young and adult
      females has only been partially addressed in the literature. Our aim was to
      investigate the gender association to vertebral shape in the thoracic and lumbar
      spine as a possible adaptation to lumbar hyperlordosis in young and adult
      females. A three-dimensional digitizer was used to measure the vertebral body
      sagittal wedging, relative spinous process thickness, and relative interfacet
      width at the T1-L5 level. Two hundred and forty complete, non-pathological
      skeletons of adults and 32 skeletons of young individuals were assessed. Three
      major results were found to be independent of age and ethnicity: (a) VB sagittal
      wedging in females was significantly less kyphotic than males from T9 to L2 (T11
      excluded) with a cumulative mean difference of 8.8 degrees ; (b) females had a
      significantly relatively thinner lumbar spinous processes and (c) females had a
      relatively wider superior interfacet distance (T9-T10 and L1-L4) than males. We
      conclude that the combination of less kyphotic VB wedging in the lower thoracic
      and upper lumbar vertebrae, relatively greater interspinous space and larger
      interfacet width in the lumbar spine in females are key architectural elements in
      the lumbar hyperlordosis in females and may compensate for the bipedal obstetric
      load during pregnancy.

PMID- 20033741
TI  - Unusual bone formation in the anterior rim of foramen magnum: cause, effect and
      treatment.
AB  - A rare case of proatlas segmental abnormality resulting in a bony mass in the
      anterior rim of the foramen magnum is studied. Case report of a 19-year-old
      female showed a progressive weakness of all four limbs for about 3 years. When
      admitted she could not perform any useful activities by herself. Investigations
      revealed an unusual bone growth in the region of the anterior rim of foramen
      magnum that resulted in severe cord compression. The abnormal bone formation
      involved the lower end of clivus, the tip of the odontoid process and the
      posterior arch of the atlas. Dynamic imaging did not reveal any clear evidence of
      instability. Following transoral decompression and posterior fixation, the
      patient showed dramatic and lasting clinical recovery. Conclusions were drawn as
      follows. Anomalies of the most caudal part of the occipital sclerotomes due to
      the failure of proatlas segmentation can be the cause of an abnormal bone mass in
      the anterior rim of foramen magnum. Transoral decompression, followed by
      posterior atlantoaxial fixation, results in neurological recovery and provides
      lasting cure from the problem.

PMID- 20033743
TI  - Secular trend of genome types of respiratory adenovirus type 3 during 1983-2005:
      a study from Taiwan.
AB  - Genome type analysis of adenovirus type 3 (Ad3) in Taiwan identified four types
      (Ad3a, Ad3a2, Ad3a1, Ad3-7) during 1983-2005. Ad3a was the major type during 1983
      1999, while Ad3a2 was the predominant type from 2001 to 2005. Phylogenetic
      analysis of the hexon gene of 23 isolates revealed that most Ad3a2 and Ad3-7
      isolates belonged to one cluster, and most Ad3a isolates to the other cluster.
      The clinical manifestations included respiratory tract infections, acute
      gastroenteritis, hand-foot-and-mouth disease, febrile convulsion and
      pharyngoconjunctival fever. In conclusion, Ad3a2 has replaced Ad3a as the most
      common genome type in Taiwan since 2001.

PMID- 20033742
TI  - Genetic association of the interaction between the BDNF and GSK3B genes and major
      depressive disorder in a Chinese population.
AB  - Alterations in brain-derived neurotrophic factor (BDNF)-signaling pathways may
      play an important role in the pathophysiology of major depressive disorder (MDD).
      Several lines of evidence have suggested that gene-gene interactions may confer
      susceptibility to MDD. The aim of this study was to analyze the single and
      combined effects of genes in the BDNF signal-transduction pathway on MDD in a
      Chinese population. We recruited 447 patients with MDD and 432 age- and gender
      matched control subjects. Five SNPs in three BDNF signal-transduction pathway
      genes (BDNF, GSK3B and AKT1) were used in association analyses. An allelic
      association between the GSK3B SNP rs6782799 and MDD was found in our sample
      (allelic: chi(2) = 5.24, P = 0.022, corrected P = 0.107; genotypic: chi(2) =
      5.55, P = 0.062) with an odds ratio (OR) of 1.25 (95% confidence interval (CI)
      1.03-1.52). Further gene-gene interaction analyses showed a significant effect of
      a two-locus BDNF/GSK3B interaction with MDD (GSK3B rs6782799 and BDNF rs7124442)
      (corrected P = 0.011), and also for a three-locus interaction (GSK3B rs6782799,
      BDNF rs6265 and BDNF rs7124442) (corrected P = 0.019). Individuals carrying the
      combination of two risk alleles showed an OR value of 4.00 (95% CI 2.05-7.79),
      while those with the combination of three risk alleles gave the largest OR value
      of 4.46 (95% CI 2.15-9.24). Taken together, these findings support the assertion
      that the GSK3B gene is an important susceptibility factor for MDD in a Han
      Chinese population.

PMID- 20033744
TI  - The clinical effectiveness of transurethral incision of the prostate: a
      systematic review of randomised controlled trials.
AB  - PURPOSE: Transurethral incision of the prostate gland (TUIP) is perceived as a
      less morbid surgical alternative to standard transurethral resection of the
      prostate gland (TURP) for treatment of symptomatic mild to moderate benign
      prostate enlargement (BPE). We aimed to evaluate comparative clinical
      effectiveness of the two procedures. METHODS: Systematic review and meta-analysis
      of short- and long-term data from randomised controlled trials comparing TUIP
      with TURP. RESULTS: This review considered data from 795 randomised participants
      across 10 RCTs of moderate to poor quality 8 of which stated an upper limit for
      prostate size. No difference in the degree of symptomatic improvement was seen
      between the two procedures. Improvement in peak urine flow rate was lower for
      TUIP compared to TURP whilst the rate of blood transfusion and TUR syndrome was
      higher after TURP. Urinary retention, urinary tract infection, strictures and
      incontinence did not differ between the two approaches, although clinically
      important differences could not be ruled-out. TUIP was associated with a shorter
      duration of operation and length of hospital stay but a higher re-operation rate.
      CONCLUSION: TUIP and TURP appear to offer equivalent symptomatic improvement for
      men with mild to moderate BPE. Choosing TUIP involves a trade-off between the
      lower risk of peri-operative morbidity and the higher risk of subsequent re
      operation.

PMID- 20033745
TI  - Analysis of impulse adaptation in motoneurons.
AB  - Animal locomotion results from muscle contraction and relaxation cycles that are
      generated within the central nervous system and then are relayed to the periphery
      by motoneurons. Thus, motoneuron function is an essential element for
      understanding control of animal locomotion. This paper presents motoneuron input
      output relationships, including impulse adaptation, in the medicinal leech. We
      found that although frequency-current graphs generated by passing 1-s current
      pulses in neuron somata were non-linear, peak and steady-state graphs of
      frequency against membrane potential were linear, with slopes of 5.2 and 2.9
      Hz/mV, respectively. Systems analysis of impulse frequency adaptation revealed a
      static threshold nonlinearity at -43 mV (impulse threshold) and a single time
      constant (tau = 88 ms). This simple model accurately predicts motoneuron impulse
      frequency when tested by intracellular injection of sinusoidal current. We
      investigated electrical coupling within motoneurons by modeling these as three
      compartment structures. This model, combined with the membrane potential-impulse
      frequency relationship, accurately predicted motoneuron impulse frequency from
      intracellular records of soma potentials obtained during fictive swimming. A
      corollary result was that the product of soma-to-neurite and neurite-to-soma
      coupling coefficients in leech motoneurons is large, 0.85, implying that the soma
      and neurite are electrically compact.

PMID- 20033746
TI  - Functional and molecular evolution of olfactory neurons and receptors for
      aliphatic esters across the Drosophila genus.
AB  - Insect olfactory receptor (Or) genes are large, rapidly evolving gene families of
      considerable interest for evolutionary studies. They determine the responses of
      sensory neurons which mediate critical behaviours and ecological adaptations. We
      investigated the evolution across the genus Drosophila of a subfamily of Or genes
      largely responsible for the perception of ecologically relevant aliphatic esters;
      products of yeast fermentation and fruits. Odour responses were recorded from
      eight classes of olfactory receptor neurons known to express this Or subfamily in
      D. melanogaster and from homologous sensilla in seven other species. Despite the
      fact that these species have diverged over an estimated 40 million years, we find
      that odour specificity is largely maintained in seven of the eight species. In
      contrast, we observe extensive changes in most neurons of the outgroup species D.
      virilis, and in two neurons across the entire genus. Some neurons show small
      shifts in specificity, whilst some dramatic changes correlate with gene
      duplication or loss. An olfactory receptor neuron response similarity tree did
      not match an Or sequence similarity tree, but by aligning Or proteins of likely
      functional equivalence we identify residues that may be relevant for odour
      specificity. This will inform future structure-function studies of Drosophila
      Ors.

PMID- 20033747
TI  - Elucidation of insulin degrading enzyme catalyzed site specific hydrolytic
      cleavage of amyloid beta peptide: a comparative density functional theory study.
AB  - In this B3LYP study, the catalytic mechanisms for the hydrolysis of the three
      different peptide bonds (Lys28-Gly29, Phe19-Phe20, and His14-Gln15) of Alzheimer
      amyloid beta (Abeta) peptide by insulin-degrading enzyme (IDE) have been
      elucidated. For all these peptides, the nature of the substrate was found to
      influence the structure of the active enzyme-substrate complex. The catalytic
      mechanism is proposed to proceed through the following three steps: (1)
      activation of the metal-bound water molecule, (2) formation of the gem-diol
      intermediate, and (3) cleavage of the peptide bond. With the computed barrier of
      14.3, 18.8, and 22.3 kcal/mol for the Lys28-Gly29, Phe19-Phe20, and His14-Gln15
      substrates, respectively, the process of water activation was found to be the
      rate-determining step for all three substrates. The computed energetics show that
      IDE is the most efficient in hydrolyzing the Lys28-Gly29 (basic polar-neutral
      nonpolar) peptide bond followed by the Phe19-Phe20 (neutral nonpolar-neutral
      nonpolar) and His14-Gln15 (basic polar-neutral polar) bonds of the Abeta
      substrate.

PMID- 20033748
TI  - Morgagni hernia: diagnosis with multidetector computed tomography and treatment.
AB  - PURPOSE: We aimed to retrospectively evaluate morbidity, mortality and treatment
      outcomes in 12 cases of Morgagni hernia diagnosed with multidetector computed
      tomography (MDCT) and treated appropriately. METHODS: This is a retrospective
      study and data on the demographics, presenting symptoms, MDCT images, operative
      approach, morbidity and mortality were collected from hospital records. RESULTS:
      Of 12 patients with a mean age of 60 years, ten were female. The diagnosis was
      made with MDCT before surgery. All hernias were unilateral and located in the
      right part of the thorax. The contents of the hernias were omentum and colon in
      the majority of the patients, and the contents of the hernia as diagnosed with CT
      was confirmed at surgery. Six patients had surgery. Of these, one had emergency
      surgery for hernia, two laparoscopic hernia repair, three transabdominal repair
      and one transthoracic repair. CONCLUSIONS: MDCT is a good imaging technique to be
      used before surgery in that it is fast and non-invasive, helps to make an
      accurate diagnosis of Morgagni hernias and provides detailed information about
      the contents of the hernia and accompanying complications. Modern surgical
      techniques, including laparoscopy, help to achieve the repair of Morgagni hernias
      safely with short hospital stay and with little morbidity and mortality.

PMID- 20033749
TI  - Risk factors for multidrug-resistant Pseudomonas aeruginosa acquisition. Impact
      of antibiotic use in a double case-control study.

PMID- 20033750
TI  - Regulation of mRNA caspase-8 levels by anti-nuclear autoantibodies.
AB  - Apoptosis of the acinar and ductal epithelial cells of the salivary glands has
      been proposed as a mechanism possibly responsible for the impairment of the
      secretory function in Sjogren's syndrome, an organ-specific autoimmune disorder
      characterized by destruction of these glandular structures. The presence of serum
      autoantibodies (Abs) directed against the ribonucleoproteic antigens Ro and La is
      one of the classification criteria used to identify Sjogren patients, and there
      is increasing evidence of the direct involvement of Abs in tissue pathogenesis.
      Our recent report demonstrated that anti-Ro and anti-La Abs are able to trigger
      the extrinsic pathway of apoptosis in the human salivary gland cells. To better
      understand how the anti-Ro and anti-La Abs exert their apoptotic effect, human
      caspase-8 gene expression was examined in primary human salivary gland epithelial
      cell (SGEC) cultures established from biopsies of labial minor salivary glands.
      To measure mRNA expression changes of initiating caspase-8, the real-time
      polymerase chain reaction was employed. This was combined with western blot to
      study the activation of caspase-8 detecting the cleaved form of caspase-8 and the
      cleaved poly (ADP-ribose) polymerase, downstream consequences of caspases
      activation. Data obtained suggest that the anti-Ro and anti-La Abs determine a
      transcriptional up-regulation and activation of caspase-8. Study of the mRNA in
      SGEC experimental model may provide insight into the signal transduction pathway
      stimulated by anti-nuclear autoantibodies.

PMID- 20033751
TI  - The metabolic profile in patients with skin tags.
AB  - Although skin tags are associated with diabetes mellitus, insulin resistance,
      hypertension, obesity, atherogenic lipid profile, no data in the literature show
      that the presence of skin tags is associated with serum high-sensitive C-reactive
      protein, uric acid, free fatty acid and leptin level. The purpose of this study
      was to evaluate the frequency of hypertension, dyslipidemia, insulin resistance
      and obesity in patients with skin tags and to compare patients with skin tags and
      normal healthy subjects for insulin resistance, serum lipids, insulin, glucose,
      leptin, high-sensitive C-reactive protein, free fatty acid levels. We evaluated
      113 patients with skin tags and 31 healthy subjects. The two groups were compared
      with respect to BMI, lipid profile, blood pressure, insulin resistance, serum
      lipids, insulin, glucose, leptin, high-sensitive C-reactive protein, free fatty
      acid and homeostatic model assessment of insulin resistance (HOMA-IR). Total 53.9
      and 33.6% of patients with skin tags were overweight and obese, respectively. The
      frequency of hypertension 30.1%, dyslipidemia 59.3% and insulin resistance 21.2%
      were detected. HOMA-IR (P < 0.001) and serum glucose (P < 0.001), insulin (P =
      0.002), high-sensitive C-reactive protein (P = 0.001), uric acid (P = 0.001),
      free fatty acid (P = 0.002), HbA1c (P < 0.001), total cholesterol (P = 0.018),
      LDL-cholesterol (P = 0.023), and triglyceride levels (P = 0.001) were higher in
      patients with skin tags than control group. Overweight and/or obesity,
      dyslipidemia, hypertension, insulin resistance and elevated high-sensitive C
      reactive protein are seen in patients with skin tags. Skin tags may be a marker
      of increased risk of atherosclerosis and cardiovascular disease.

PMID- 20033752
TI  - VEGF-A/HGF induce Prox-1 expression in the chick embryo chorioallantoic membrane
      lymphatic vasculature.
AB  - Vascular endothelial growth factor-A (VEGF-A) and hepatocyte growth factor (HGF)
      are well known angiogenesis inductors and promoters in normal and pathologic
      conditions. Recent data showed that VEGF-A and HGF could also influence
      lymphangiogenesis but this matter has not been completely elucidated.
      Administration of VEGF-A and HGF in combination has been used to improve the
      angiogenic response in different experimental models, but their effects on
      lymphangiogenesis have not been investigated. The aim of this study was to
      characterize blood and lymphatic vascular response to VEGF-A/HGF administration.
      To this purpose, we built a pBlast VEGF-A/HGF combination suitable for in vivo
      research. By using as an experimental in vivo model the chick embryo
      chorioallantoic membrane (CAM) assay, we applied pBlast VEGF-A/HGF combination
      for 7 days. Results showed that VEGF-A/HGF combination was able to induce a
      strong angiogenic response and the expression of Prox-1 in the lymphatic
      endothelial cells of the CAM. The possible mechanisms involved have been
      speculated.

PMID- 20033753
TI  - Immunoglobulin gene locus events in epithelial cells of lactating mouse mammary
      glands.
AB  - It has been believed that the immunoglobulin (Ig) found abundantly in the
      colostrum of lactating mammalian is derived from serum or secreted by plasma
      cells present in the mammary gland. The recent finding of Ig gene rearrangements
      in breast cancer cells and benign hyperplastic breast epithelial cells suggests
      that it is likely that hyperplastic mammary gland epithelial cells during
      lactation can also produce Ig. In this study, we have demonstrated the presence
      of abundant amounts of Ig heavy and light chain transcripts in sorted cytokeratin
      18-positive mammary gland epithelial cells of lactating mice. Interestingly, we
      found two specific Igkappa variable region sequences (V(CW9)J(kappa1) and
      V(BV9)J(kappa1)) that were dominantly expressed in different strains of mice. Our
      data demonstrate that IgG is expressed by mammary gland epithelial cells of
      lactating mice, and suggest that the IgG found in murine colostrum is at least
      partially produced by the mammary gland epithelial cells.

PMID- 20033754
TI  - Parafalcine lesions in the cancer patient: diagnostic dilemma--meningioma or
      metastatic lesion?
AB  - The authors present two cases that illustrate the difficulty in radiographically
      distinguishing between meningioma and metastatic lesions in patients with known
      cancer, especially with a parafalcine tumor location. The first patient with
      known metastatic prostate cancer had imaging studies suggestive of a parafalcine
      meningioma, but after surgical resection the lesion was found to be
      histologically consistent with metastatic disease. Conversely, the second patient
      was thought to have a metastatic breast cancer lesion in the parafalcine region.
      This presumptive diagnosis based on imaging findings led the patient to undergo
      radiosurgery treatment; however, the lesion grew over a several-month course and
      was eventually resected. The pathological analysis revealed that the tumor was,
      in fact, a meningioma. Using these cases, as well as an extensive review of the
      literature, the authors highlight the difficulty in making accurate radiographic
      diagnosis of dural-based lesions, especially in the parafalcine location, where
      meningiomas are commonly found but can have multiple entities mimicking their
      presentation. Caution must be used in managing patients with presumed parafalcine
      meningiomas or metastatic disease that have no histological diagnosis.

PMID- 20033755
TI  - Intraoperative perforation of Descemet's membrane during "big bubble" deep
      anterior lamellar keratoplasty.
AB  - To analyze the reasons for intraoperative perforation of Descemet's membrane
      during deep anterior lamellar keratoplasty (DALK) during the learning curve. DALK
      was attempted in 35 eyes of 33 patients with pathologies involving the corneal
      stroma and sparing of Descemet's membrane (DM), including patients with
      keratoconus, corneal stromal dystrophies and healed keratitis. The surgical plan
      included complete removal of the corneal stroma using the "big bubble" technique
      for exposing Descemet's membrane followed by grafting of a full-thickness corneal
      stromal lenticule. DALK was converted into full-thickness penetrating
      keratoplasty in eight eyes (23%), which included patients with keratoconus (n =
      6), macular corneal dystrophy (n = 1) and healed keratitis (n = 1). Main reasons
      for conversion were perforation of the DM due to excessive air injection (four
      eyes) and improper surgical maneuvers (three eyes). One case had deposits on
      Descemet's membrane upon exposure of the DM. A successful penetrating
      keratoplasty could be performed in all eight eyes. During the learning curve,
      excessive air injection and inappropriate surgical maneuvers may complicate a
      DALK resulting in conversion to penetrating keratoplasty.

PMID- 20033756
TI  - CMV retinitis after intravitreal triamcinolone acetonide injection in a patient
      with Behcet's uveitis.
AB  - We report the case of a patient with Behcet's uveitis who developed
      cytomegalovirus (CMV) retinitis after intravitreal triamcinolone acetonide (IVTA)
      injection. We reviewed the patient's chart for the purpose of this report. An
      IVTA injection was performed for treatment of severe panuveitis in the left eye
      of a 30-year-old male patient with Behcet's disease. Systemic treatment included
      high dose corticosteroid and azathioprine. Fourteen weeks after IVTA, extensive
      areas of necrotizing retinitis developed in the left eye. Polymerase chain
      reaction of serum and vitreous samples was positive for CMV DNA. Serum anti-CMV
      IgG was positive, IgM was negative, anti-HIV antibody was negative, complete
      blood count was normal, and CD4 count was 1,060 cells/MUl. The patient responded
      well to intravitreal ganciclovir injection performed twice and intravenous
      ganciclovir treatment administered for five weeks. Local immunosuppression with
      IVTA may cause CMV retinitis. Awareness of this serious complication is important
      for correct diagnosis and treatment.

PMID- 20033757
TI  - Environmental benefits of using magnesium carbonate minerals as new wildfire
      retardants instead of commercially available, phosphate-based compounds.
AB  - A serial batch leaching experiment has been carried out to evaluate the release
      of elements from the ash of Pinus halepensis needles burned under two test
      conditions-with and without treatment of the forest species with the carbonate
      minerals (huntite and hydromagnesite) in aqueous solution (pH 6). The ash (before
      and after leaching) and leachates were analyzed using atomic absorption
      spectroscopy and X-ray diffraction. Compared with data from samples treated with
      the commercially available, phosphate-based fire retardant diammonium phosphate
      (DAP), we found that use of huntite or hydromagnesite was much more successful in
      obstructing the release of the toxic elements present in the ash, probably
      because of the alkaline conditions resulting from decomposition of the minerals
      during burning. In contrast, DAP tended to be more able to facilitate the
      extraction of some toxic metals (e.g., Zn, Cu, Mn), probably because of the
      acidic conditions resulting from its decomposition to phosphoric acid. Data from
      this study thus lend strong support to the use of magnesium carbonate minerals as
      new wildfire retardants, because they were shown to be more friendly to the
      environment (e.g., soil, ground, and underground water streams) than those
      currently in use (e.g., phosphate or sulfate salt type).

PMID- 20033760
TI  - The temporality of "chronic" mental illness.
AB  - Although multiple concepts of time can be found in psychiatric discourses and
      practices, the notion of time as an absolute category seems to predominate. In
      particular, the notion of "chronicity" implies the persistence of symptoms over
      the temporal course of a disease, thereby following a logic that conceptualizes
      time as an objective and universal measure. I argue that such a notion of time
      impedes the development of patients and the metrics by which to map change. This
      article, therefore, aims to present a different concept of time that should
      enable dealing with "chronic" mental illness in more flexible and creative ways.
      A case study of an everyday psychiatric routine is presented, followed by an in
      depth analysis of its temporal implications. I conceptualize the notion of time
      as an extended field, being relationally and intersubjectively structured and
      linked to performed activities. Such a notion of time needs to be seen as a
      flexible and fluid matrix that possesses the character of an event-oriented and
      productive space. This conception favors an individualized temporality of change,
      suggesting concrete therapeutic procedures that can be implemented in clinical
      practice.

PMID- 20033758
TI  - Inhibin/activin-betaE subunit in normal and malignant human cervical tissue and
      cervical cancer cell lines.
AB  - Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two
      possible beta-subunits (betaA or betaB), with substantial roles in human
      reproduction and in endocrine-responsive tumours. Recently a novel beta subunit
      named betaE was described, although it is still unclear if normal or cancerous
      cervical epithelial cells as well as cervical cancer cell lines can synthesise
      the novel inhibin-betaE subunit. About 4 normal cervical tissue samples together
      with 10 specimens of well-differentiated squamous cervical cancer and
      adenocarcinoma of the cervix were immunohistochemical analyzed. Additionally, two
      cervical carcinoma cell lines (HeLa and CaSki) were analyzed by
      immunofluorescence and RT-PCR for the expression of this novel subunit. We
      demonstrated for the first time an immunolabelling of the inhibin-betaE subunit
      in normal and malignant cervical tissue, as well as cervical cancer cells.
      Although the physiological role is still quite unclear in cervical tissue,
      inhibin-betaE might play important roles in carcinogenesis. Moreover, the
      synthesis of this subunit in cervical carcinoma cell lines of squamous and
      glandular epithelial origins also allows the use of these cell lines in
      elucidating its functions in cervical cancer pathogenesis. However, since the
      expression of the inhibin-betaE is minimal in HeLa cells as assessed by
      immunofluorescence and RT-PCR, the CaSki cell line might be a better model for
      further functional experiments regarding cervical cancer pathogenesis.

PMID- 20033761
TI  - Special issue introduction: the place of self-harm in adolescent development.

PMID- 20033763
TI  - Correlates of unprotected anal sex at last sexual episode: analysis from a
      surveillance study of men who have sex with men in Montreal.
AB  - Recent increases in rates of unprotected anal sex (UAS) among men who have sex
      with men (MSM) signal the need to continually refine our understanding of factors
      associated with risky sexual behavior. Data were collected using a questionnaire
      eliciting information about the last sexual episode (LSE) with another man in the
      past 6 months. Logistic regression was used to identify both event-level and
      background correlates of UAS at LSE. 965 participants who reported having sex
      with a partner with whom they were not in a couple relationship at LSE were
      studied. Several event-level variables were significantly associated with UAS
      after adjusting for background factors, including finding the partner at LSE
      sexually attractive and using alcohol or cocaine at LSE. Our findings parallel
      the results of other HIV prevention studies which have highlighted the importance
      of interpersonal factors that influence risk-taking at the moment of a sexual act
      among MSM.

PMID- 20033764
TI  - Improving the linkage between research and system change: making it real.

PMID- 20033762
TI  - Health-Related Quality of Life in children with autism spectrum disorders:
      results from the autism treatment network.
AB  - We examined data collected as a part of the Autism Treatment Network, a group of
      15 autism centers across the United States and Canada. Mean Health-Related
      Quality of Life (HRQoL) scores of the 286 children assessed were significantly
      lower than those of healthy populations (according to published norms). When
      compared to normative data from children with chronic conditions, children with
      ASD demonstrated worse HRQoL for total, psychosocial, emotional and social
      functioning, but did not demonstrate differing scores for physical and school
      functioning. HRQoL was not consistently related to ASD diagnosis or intellectual
      ability. However, it was consistently related to internalizing and externalizing
      problems as well as repetitive behaviors, social responsiveness, and adaptive
      behaviors. Associations among HRQoL and behavioral characteristics suggest that
      treatments aimed at improvements in these behaviors may improve HRQoL.

PMID- 20033765
TI  - Biochemical genetics of opossum aldehyde dehydrogenase 3: evidence for three
      ALDH3A-like genes and an ALDH3B-like gene.
AB  - Mammalian ALDH3 isozymes participate in peroxidic and fatty aldehyde metabolism,
      and in anterior eye tissue UV-filtration. BLAT analyses were undertaken of the
      opossum genome using rat ALDH3A1, ALDH3A2, ALDH3B1, and ALDH3B2 amino acid
      sequences. Two predicted opossum ALDH3A1-like genes and an ALDH3A2-like gene were
      observed on chromosome 2, as well as an ALDH3B-like gene, which showed similar
      intron-exon boundaries with other mammalian ALDH3-like genes. Opossum ALDH3
      subunit sequences and structures were highly conserved, including residues
      previously shown to be involved in catalysis and coenzyme binding for rat
      ALDH3A1. Eleven glycine residues were conserved for all of the opossum ALDH3-like
      sequences examined, including two glycine residues previously located within the
      stem of the rat ALDH3A1 active site funnel. Phylogeny studies of human, rat,
      opossum, and chicken ALDH3-like sequences indicated that the common ancestor for
      ALDH3A- and ALDH3B-like genes predates the appearance of birds during vertebrate
      evolution.

PMID- 20033766
TI  - Lack of association between CYP17 MspA1 polymorphism and breast cancer risk: a
      meta-analysis of 22,090 cases and 28,498 controls.
AB  - Epidemiological studies have evaluated the association between CYP17 MspA1
      polymorphism and breast cancer risk. However, the results remain conflicting
      rather than conclusive. To derive a more precise estimation of the relationship,
      we performed this meta-analysis. Systematic searches of the PubMed and Medline
      databases were performed. A total of 35 studies including 22,090 cases and 28,498
      controls were identified. Genotype distributions of CYP17 in the controls of all
      studies were in agreement with Hardy-Weinberg equilibrium (HWE) except for three
      studies. When all 35 studies were pooled into the meta-analysis, there was no
      evidence for significant association between CYP17 MspA1 polymorphism and breast
      cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96-1.04; for A2/A2 vs.
      A1/A1: OR = 1.03, 95% CI = 0.97-1.08; for dominant model: OR = 1.01, 95% CI =
      0.97-1.05; for recessive model: OR = 1.03, 95% CI = 0.98-1.08). In the subgroup
      analyses by ethnicity, menopausal status and source of controls, no significant
      associations were found in all genetic models. When sensitivity analyses were
      performed by excluding HWE-violating studies, all the results were not materially
      altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1
      polymorphism is not associated with increased breast cancer risk.

PMID- 20033767
TI  - Current evidence on the relationship between polymorphisms in the COX-2 gene and
      breast cancer risk: a meta-analysis.
AB  - The association between single-nucleotide polymorphisms (SNPs) in the COX-2 gene
      and breast cancer risk is still ambiguous. We here try to derive a more precise
      estimation of the relationship by performing a meta-analysis based on currently
      available evidence from literature. More than 15 SNPs have been studied, and the
      most studied genetic variants were rs5275, rs5277, and rs20417. Crude odds ratios
      (ORs) with 95% confidence intervals (CIs) were used to assess the strength of
      association between each polymorphism and breast cancer risk under the codominant
      model, dominant model, and recessive model, respectively (nine studies with 6,968
      cases and 9,126 controls for rs5275; three studies with 2,901 cases and 3,463
      controls for rs20417; two studies with 5,551 cases and 6,208 controls for
      rs5277). No overall significant associations were observed in single-locus
      analysis between the three polymorphisms of COX-2 and breast cancer risk, though
      a borderline significant increased risk of breast cancer was detected with rs5277
      in a recessive model (OR: 1.217, 95% CI: 0.958-1.547, P = 0.107). The results
      were not changed when studies were stratified by ethnicity. In conclusion, the
      present meta-analysis suggests that none of the most studied three SNPs (rs5275,
      rs20417, and rs5277) in the COX-2 gene is a conspicuous low-penetrant risk factor
      for developing breast cancer. There is a need for further large studies into the
      role of these polymorphisms (especially rs5277) and other potentially functional
      polymorphisms/haplotypes in the COX-2 gene as breast cancer risk modifiers.

PMID- 20033768
TI  - Role of endothelial progenitor cells in breast cancer angiogenesis: from
      fundamental research to clinical ramifications.
AB  - Blood vessel formation (neovascularization) in tumors can occur through two
      mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from
      proliferation and sprouting of existing blood vessels close to the tumor, while
      vasculogenesis is believed to arise from recruitment of circulating cells,
      largely derived from the bone marrow, and de novo clonal formation of blood
      vessels from these cells. Increasing evidence in animal models indicate that bone
      marrow-derived endothelial precursor cells (EPC) can contribute to tumor
      angiogenesis. This review aims to collate existing literature and provide an
      overview on the current knowledge of EPC involvement in breast cancer
      angiogenesis. We also discuss recent attempts to use EPC as biomarker and
      therapeutic target in clinical trials.

PMID- 20033769
TI  - Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2
      mutation carriers? Long-term results and review of the literature.
AB  - As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, we
      investigated after long-term follow-up whether mutation status influenced the
      rate of ipsilateral and contralateral breast cancers after breast-conserving
      treatment (BCT). BRCA1 and BRCA2 genes were screened for germline mutations in
      131 patients with a family history of breast and/or ovarian cancer who had
      undergone BCT and radiotherapy. Patients were matched to 261 controls with
      sporadic breast cancer according to age at diagnosis and year of treatment.
      Controls were followed up for at least as long as the interval between diagnosis
      and genetic screening in familial cases. Rates of ipsilateral and contralateral
      cancer between groups were compared by the log-rank test. The BRCA1/2 mutations
      occurred in 20.6% of tested patients. Tumours in mutation carriers were more
      likely to be grade III (P < 10(-4)) and oestrogen receptor negative (P = 0.005)
      than in non-carriers and controls. Overall median follow-up was 161 months. There
      was no significant difference in ipsilateral tumours between mutation carriers,
      non-carriers and controls (P = 0.13). On multivariate analysis, age was the most
      significant predictor for ipsilateral recurrence (P < 10(-3)). The rate of
      contralateral cancer was significantly higher in familial cases: 40.7% (mutation
      carriers), 20% (non-carriers), and 11% (controls) (P < 10(-4)). After 13.4 years
      of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers
      than in non-carriers or controls. As tumours in BRCA1/2 mutation carriers might
      be more sensitive to radiation, BCT is a possible treatment option.

PMID- 20033770
TI  - The functional promoter polymorphism (-842G>C) in the PIN1 gene is associated
      with decreased risk of breast cancer in non-Hispanic white women 55 years and
      younger.
AB  - PIN1, an isomerase that causes conformational changes in proteins, plays an
      important role in mammary epithelial cell growth both physiologically and
      pathologically. Thus, genetic variants in the PIN1 gene may alter protein
      function and cancer risk. We have previously demonstrated an association between
      a PIN1 promoter variant (-842G>C; rs2233678) and risk of squamous cell carcinoma
      of the head and neck, a finding supported by additional functional data. In the
      present study, we genotyped two promoter single nucleotide polymorphisms (SNPs) (
      842G>C, rs2233678 and -667T>C, rs2233679) and one synonymous SNP (Gln33Gln; G>A,
      rs2233682) in exon 2 to evaluate their associations with risk of sporadic breast
      cancer in non-Hispanic white women 55 years and younger. We found that the
      carriers of -842C variant alleles had decreased risk of breast cancer with an
      adjusted odd ratio (OR) of 0.67 and 95% confidence interval (CI) of 0.50-0.90.
      This reduced risk was more evident in women after reproductive age of 45 (OR =
      0.63, 95% CI = 0.42-0.93), ever-smokers (OR = 0.56, 95% CI = 0.36-0.88), and ever
      drinkers (OR = 0.67, 95% CI = 0.45-0.99). No such associations were observed for
      PIN1 -667T>C and PIN1 Gln33Gln. However, the haplotypes of these three SNPs were
      also associated with reduced risk of breast cancer. In conclusion, the PIN1
      polymorphisms may contribute to the etiology of sporadic breast cancer in non
      Hispanic white women 55 years and younger. Further validation in large population
      based studies is needed.

PMID- 20033771
TI  - The potential of biomonitoring of air quality using leaf characteristics of white
      willow (Salix alba L.).
AB  - In this study, we assess the potential of white willow (Salix alba L.) as
      bioindicator for monitoring of air quality. Therefore, shoot biomass, specific
      leaf area, stomatal density, stomatal pore surface, and stomatal resistance were
      assessed from leaves of stem cuttings. The stem cuttings were introduced in two
      regions in Belgium with a relatively high and a relatively low level of air
      pollution, i.e., Antwerp city and Zoersel, respectively. In each of these
      regions, nine sampling points were selected. At each sampling point, three stem
      cuttings of white willow were planted in potting soil. Shoot biomass and specific
      leaf area were not significantly different between Antwerp city and Zoersel.
      Microclimatic differences between the sampling points may have been more
      important to plant growth than differences in air quality. However, stomatal pore
      surface and stomatal resistance of white willow were significantly different
      between Zoersel and Antwerp city. Stomatal pore surface was 20% lower in Antwerp
      city due to a significant reduction in both stomatal length (-11%) and stomatal
      width (-14%). Stomatal resistance at the adaxial leaf surface was 17% higher in
      Antwerp city because of the reduction in stomatal pore surface. Based on these
      results, we conclude that stomatal characteristics of white willow are
      potentially useful indicators for air quality.

PMID- 20033772
TI  - Discrimination, perceived social inequity, and mental health among rural-to-urban
      migrants in China.
AB  - Status-based discrimination and inequity have been associated with the process of
      migration, especially with economics-driven internal migration. However, their
      association with mental health among economy-driven internal migrants in
      developing countries is rarely assessed. This study examines discriminatory
      experiences and perceived social inequity in relation to mental health status
      among rural-to-urban migrants in China. Cross-sectional data were collected from
      1,006 rural-to-urban migrants in 2004-2005 in Beijing, China. Participants
      reported their perceptions and experiences of being discriminated in daily life
      in urban destination and perceived social inequity. Mental health was measured
      using the symptom checklist-90 (SCL-90). Multivariate analyses using general
      linear model were performed to test the effect of discriminatory experience and
      perceived social inequity on mental health. Experience of discrimination was
      positively associated with male gender, being married at least once, poorer
      health status, shorter duration of migration, and middle range of personal
      income. Likewise, perceived social inequity was associated with poorer health
      status, higher education attainment, and lower personal income. Multivariate
      analyses indicate that both experience of discrimination and perceived social
      inequity were strongly associated with mental health problems of rural-to-urban
      migrants. Experience of discrimination in daily life and perceived social
      inequity have a significant influence on mental health among rural-to-urban
      migrants. The findings underscore the needs to reduce public or societal
      discrimination against rural-to-urban migrants, to eliminate structural barriers
      (i.e., dual household registrations) for migrants to fully benefit from the urban
      economic development, and to create a positive atmosphere to improve migrant's
      psychological well-being.

PMID- 20033773
TI  - Fidelity and recovery-orientation in assertive community treatment.
AB  - There has been increasing commentary about the degree to which Assertive
      Community Treatment (ACT) teams provide recovery-oriented services, often
      centered around the question of the use of coercion. The present study was
      designed to contribute to this discussion through an examination of recovery
      oriented service provision and ACT fidelity among 67 teams in the province of
      Ontario, Canada. The findings indicated a moderate to high degree of recovery
      orientation in service provision, with no significant relationship between ACT
      fidelity and consumer and family/key support ratings of recovery orientation. A
      significant relationship was found, however, between the 'nature of services'
      domain of the Dartmouth Assertive Community Treatment Scale (DACTS) and ratings
      of recovery orientation provided by staff and ACT coordinators. These findings
      extend the existing dialogue regarding the evaluation of ACT intervention process
      factors and indicate that current measures of fidelity may not be adequately
      addressing dimensions of recovery-oriented service provision.

PMID- 20033774
TI  - Post stroke depression: treatments and complications in a young adult.
AB  - Post-stroke depression has been noted to be one of the most frequent
      complications of stroke with an estimated prevalence of as high as 80%. However,
      the incidence of stroke in the young is extremely low and evidence based therapy
      for this complication is quite limited. The case of a 28-year-old woman who
      experienced a basilar artery vasospasmic stroke resulting in anoxic brain injury
      to the midbrain and paramedian thalamus is presented, along with a literature
      review of psychiatric complications of this injury to include post-stroke
      depression (PSD). Therapeutic modalities such as TCAs, SSRIs, atypical
      antipsychotics and stimulant medications are also reviewed as these medications
      may aid in the treatment of such patients but may also contribute to psychiatric
      sequelae.

PMID- 20033775
TI  - Inbred strain-specific effects of exercise in wild type and biglycan deficient
      mice.
AB  - Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to
      changes in the amount and quality of bone. Altered tissue strength in C57BL6/129
      (B6;129) KO mice, a property which is independent of tissue quantity, suggests
      that deficiencies in tissue quality are responsible. However, the response to bgn
      deficiency is inbred strain-specific. Mechanical loading influences bone matrix
      quality in addition to any increase in bone mass or change in bone formation
      activity. Since many diseases influence the mechanical integrity of bone through
      altered tissue quality, loading may be a way to prevent and treat extracellular
      matrix deficiencies. C3H/He (C3H) mice consistently have a less vigorous response
      to mechanical loading vs. other inbred strains. It was therefore hypothesized
      that the bones from both wild type (WT) and KO B6;129 mice would be more
      responsive to exercise than the bones from C3H mice. To test these hypotheses at
      11 weeks of age, following 21 consecutive days of exercise, we investigated cross
      sectional geometry, mechanical properties, and tissue composition in the tibiae
      of male mice bred on B6;129 and C3H backgrounds. This study demonstrated inbred
      strain-specific compositional and mechanical changes following exercise in WT and
      KO mice, and showed evidence of genotype-specific changes in bone in response to
      loading in a gene disruption model. This study further shows that exercise can
      influence bone tissue composition and/or mechanical integrity without changes in
      bone geometry. Together, these data suggest that exercise may represent a
      possible means to alter tissue quality and mechanical deficiencies caused by many
      diseases of bone.

PMID- 20033776
TI  - Effect of spiral flow on the transport of oxygen in the aorta: a numerical study.
AB  - To test the hypothesis that the spiral flow pattern in the human aorta may play a
      beneficial role in the transport of oxygen, hence sparing the ascending aorta
      from atherosclerosis, a comparative study on the distribution of oxygen flux to
      the arterial wall was carried out numerically for three aorta models. The first
      one (Model 1) was constructed based on MRI images of a human aorta acquired in
      vivo. The second (Model 2) was made the same as Model 1 but without the three
      branches. The third (Model 3) was similar to Model 2 only with the aortic torsion
      removed. The results showed that without the torsion, the flow fashion in Model 3
      was very different from the swirling flows in Models 1 and 2 and exhibited the
      typical characteristics of Dean flow with two symmetrical helical structures. In
      Models 1 and 2, the average Sherwood number (Sh) in the ascending aorta with the
      presence of a strong spiral flow was not only higher than that in the inner wall
      of the descending aorta where the spiral flow faded out, but also generally
      higher than that in Model 3. The comparison between Models 2 and 3 demonstrated
      that the averaged Sh from ascending aorta to aortic arch was relatively higher
      for Model 2. In conclusion, the spiral or swirling flow may have certain
      physiological significance in the aorta and play a positive role in the transport
      of oxygen by enhancing oxygen flux to the arterial wall.

PMID- 20033778
TI  - Powering an implantable minipump with a multi-layered printed circuit coil for
      drug infusion applications in rodents.
AB  - We report the use of a multi-layer printed coil circuit for powering (36-94 mW)
      an implantable microbolus infusion pump (MIP) that can be activated remotely for
      use in drug infusion in nontethered, freely moving small animals. This
      implantable device provides a unique experimental tool with applications in the
      fields of animal behavior, pharmacology, physiology, and functional brain
      imaging. Two different designs are described: a battery-less pump usable when the
      animal is inside a home-cage surrounded by a primary inductive coil and a pump
      powered by a rechargeable battery that can be used for studies outside the home
      cage. The use of printed coils for powering of small devices by inductive power
      transfer presents significant advantages over similar approaches using hand-wound
      coils in terms of ease of manufacturing and uniformity of design. The high
      efficiency of a class-E oscillator allowed powering of the minipumps without the
      need for close physical contact of the primary and secondary coils, as is
      currently the case for most devices powered by inductive power transfer.

PMID- 20033779
TI  - Mathematical modeling of electrocardiograms: a numerical study.
AB  - This paper deals with the numerical simulation of electrocardiograms (ECG). Our
      aim is to devise a mathematical model, based on partial differential equations,
      which is able to provide realistic 12-lead ECGs. The main ingredients of this
      model are classical: the bidomain equations coupled to a phenomenological ionic
      model in the heart, and a generalized Laplace equation in the torso. The
      obtention of realistic ECGs relies on other important features--including heart
      torso transmission conditions, anisotropy, cell heterogeneity and His bundle
      modeling--that are discussed in detail. The numerical implementation is based on
      state-of-the-art numerical methods: domain decomposition techniques and second
      order semi-implicit time marching schemes, offering a good compromise between
      accuracy, stability and efficiency. The numerical ECGs obtained with this
      approach show correct amplitudes, shapes and polarities, in all the 12 standard
      leads. The relevance of every modeling choice is carefully discussed and the
      numerical ECG sensitivity to the model parameters investigated.

PMID- 20033777
TI  - Comparison of artery organ culture and co-culture models for studying endothelial
      cell migration and its effect on smooth muscle cell proliferation and migration.
AB  - Arterial restenosis associated with intimal hyperplasia is the major cause of
      long-term failure of vascular interventions. Endothelium injury and the
      proliferation and migration of smooth muscle cells (SMC) are key events in the
      development of intimal hyperplasia. The objectives of this study were to develop
      an ex vivo artery injury model for studying endothelial cell (EC) migration and
      to compare it with an in vitro co-culture arterial wall injury model in terms of
      the effect of flow on EC migration and its effect on SMC migration and
      proliferation. Our results demonstrated that shear flow improves
      reendothelialization in the injured area by promoting EC migration. The migration
      distance of ECs is much smaller in the arteries than in an in vitro cell culture
      model (3.57+/-1.29 mm vs. 5.2+/-1.4 cm, p<0.001). SMC proliferation was
      significantly less in the EC intact and reendothelialization areas than in the EC
      denuded areas indicating that reendothelialization suppresses SMC proliferation.
      Our models provide a new approach to study techniques to enhance endothelium
      healing.

PMID- 20033781
TI  - The old book switcheroo: or anatomy of a delusion.
AB  - In this paper, an aging baby boomer "tells all" about his personal experience
      with some of the "pitfalls of organized religion," as observed from his somewhat
      unusual perspective as a Jew by birth and a Roman Catholic by choice, and a
      lifelong Asperger's sufferer, the butt of practical jokes in a variety of
      juvenile and adult settings. His conclusion, echoing H.L. Mencken's famous
      statement that "the cure for the evils of democracy is more democracy," is that
      the best antidote to these "pitfalls" may be found simply in the responsible
      practice of religion, including both Judaism and Christianity. The author also
      believes his own survival in life despite some "ogres and tricksters" along the
      way validates the Jungian philosophy of synchronicity. He believes that the
      storms of life are best weathered by accepting them as parts of a Merciful
      Providence's "vast eternal plans" for all His children on Earth.

PMID- 20033783
TI  - The zebrafish as a model organism for the study of apoptosis.
AB  - Apoptosis plays important roles in embryogenesis, tissue homeostasis, and immune
      system regulation. The zebrafish (Danio rerio) is a powerful vertebrate model
      organism that has been extensively used to study apoptotic cell death during
      normal development and under conditions of cellular stress. In the past 5 years,
      a detailed picture has begun to emerge of the molecular underpinnings of the cell
      intrinsic and the cell-extrinsic apoptosis signaling pathways in zebrafish. We
      begin this review with an introduction to the techniques and experimental
      approaches that are used to study apoptosis in zebrafish. We follow with a
      general overview of developmental apoptosis during zebrafish embryogenesis.
      Finally, we present a comprehensive review of the intrinsic and extrinsic
      apoptosis pathways in zebrafish, focusing on the high degree of conservation with
      humans and other mammals. Recent publications that draw upon the unique
      advantages of the zebrafish system to study novel aspects of apoptosis regulation
      and function are highlighted throughout.

PMID- 20033782
TI  - Targeting 14-3-3 protein, difopein induces apoptosis of human glioma cells and
      suppresses tumor growth in mice.
AB  - 14-3-3 protein has emerged as critical regulators of diverse cellular responses.
      Previous studies found that strong 14-3-3 protein expression was observed and
      associated with tumor genesis and progression in glioma. Here, we further
      elucidated the role of 14-3-3 protein in apoptosis of human glioma U251 and U87
      cells by global inhibition of 14-3-3 functions with a general 14-3-3 antagonist,
      difopein. In vitro, morphological observation and DNA laddering assay showed that
      difopein-treated glioma cells displayed outstanding apoptosis characteristics,
      such as nuclear fragmentation, appearance of membrane-enclosed apoptotic bodies
      and DNA laddering fragment. Moreover, flow cytometric detection of
      phosphatidylserine externalization indicated that difopein-induced apoptosis
      occurred in a time-dependent manner. Interestingly, inhibiting 14-3-3 with small
      interfere RNA also induce apoptosis of human glioma U251 cells. Furthermore, RT
      PCR and western blot assay further substantiated that difopein had strong effects
      to induce glioma cell apoptosis through down-regulating Bcl-2, up-regulating Bax
      and activating caspase-9 and caspase-3. In vivo, retroviral vector was
      constructed and retroviral-mediated transfer of difopein to glioma was implanted
      in nude mice. Difopein effectively hindered proliferation and triggered apoptosis
      of tumor cells implanted into nude mice. This work not only reveals a critical
      role of 14-3-3 in apoptosis suppression in glioma cells, but also identifies and
      validates 14-3-3 as a potential molecular target for anticancer therapeutic
      development.

PMID- 20033785
TI  - The relationship between myocardial SPECT and fractional flow reserve: is it
      drifting apart?

PMID- 20033784
TI  - CT perfusion angiography; beware of artifacts!

PMID- 20033786
TI  - Communicating about the experience of pain and fatigue in disability.
AB  - PURPOSE: To examine the experiences of people with chronic disabling conditions
      as they communicate with health care providers about pain and fatigue. METHOD:
      Twenty-three adults with a variety of chronic disabling conditions participated
      in 5 focus groups. The following issues were raised: tell me about your
      pain/fatigue; what things go along with pain/fatigue? how do you talk about
      pain/fatigue with your health care provider (HCP)? What should your HCP know that
      they do not ask you about? RESULTS: Results of qualitative analysis suggested two
      major themes. The first theme was labeled "Putting it in words" and suggests that
      both pain and fatigue are described in many ways, including the dimensions of
      type, intensity, level of interference and temporal aspects. Participants
      reported difficulty with responding to a single question that asked them to
      assign a number to their level of pain or fatigue. The second theme was labeled,
      "Let's talk about it" and suggested that participants wanted HCPs "to listen and
      believe me when I describe my experience". They wanted to be asked about how pain
      or fatigue interferes with life and about compensatory strategies rather than
      being asked to rate symptom intensity. Participants wished to be viewed as
      experts and to be actively involved in decisions about their health care.
      CONCLUSIONS: Pain and fatigue were viewed as having many facets that are
      associated in complex ways with other aspects of the health/disability condition.
      From the participants' perspective, assignment of a pain intensity rating does
      not represent the complexity of their pain experience. Suggestions are provided
      for HCPs when communicating about pain and fatigue with people with chronic
      conditions.

PMID- 20033787
TI  - A distinct mutation on the alternative splice site of APC exon 9 results in
      attenuated familial adenomatous polyposis phenotype.
AB  - A subset of APC mutation carriers shows a milder familial adenomatous polyposis
      phenotype (attenuated FAP) developing smaller number of polyps and colorectal
      cancer at an older age. It seems that a different mechanism to carcinogenesis is
      initiated according to the initial site of the germline mutation. The APC gene of
      a female patient with AFAP phenotypic features was analysed. A novel mutation
      located on the alternatively splice site of exon 9 was identified. This is the
      first reported mutation in the specific site. Transcripts characterization
      revealed disruption of splicing occurring within exon 9, resulting in the
      expression of a shorter mRNA transcript, which surprisingly does not affect the
      ratio between the two wild type transcripts, as well as the production of wild
      type short isoform by the mutant allele. The short wild type isoform, produced by
      the mutant allele, needs to be inactivated, on top of the wild type allele, for
      colorectal cancer to develop. These observations enhance the 'three hit
      hypothesis' and indicate that a distinct mechanism for the adenoma to carcinoma
      sequence should be followed, for truncated mutations taking place on the
      borderline of the alternatively spliced exon 9 of the APC gene, as well.

PMID- 20033788
TI  - A voxelized model of direct infusion into the corpus callosum and hippocampus of
      the rat brain: model development and parameter analysis.
AB  - Recent experimental studies have shown convective-enhanced delivery (CED) to be
      useful for transporting macromolecular therapeutic agents over large tissue
      volumes in the central nervous system (CNS). There are limited tools currently
      available for predicting tissue distributions in the brain. We have developed a
      voxelized modeling methodology in which CNS tissues are modeled as porous media,
      and transport properties and anatomical boundaries are determined semi
      automatically on a voxel-by-voxel basis using diffusion tensor imaging (DTI). By
      using this methodology, 3D extracellular transport models of the rat brain were
      developed. Macromolecular tracer distributions following CED in two different
      infusion sites (corpus callosum and hippocampus) were predicted. Sensitivity of
      models to changes in infusion parameters, transport properties, and modeling
      parameters was determined. Predicted tracer distributions were most sensitive to
      changes in segmentation threshold, DTI resolution, tissue porosity, and infusion
      site. This DTI-based voxelized modeling methodology provides a potentially rapid
      means of estimating CED transport.

PMID- 20033789
TI  - Microwave applicator for hyperthermia treatment on in vivo melanoma model.
AB  - In this article, we evaluated a planar microwave applicator for in vivo
      superficial hyperthermia treatments on small tumors in the mouse mimicking
      treatments for human neoplasms. The design of the applicator, was challenged by
      the small dimensions of the tumors and unwanted diffusion of heating in the tumor
      bearing animals. The required solution was to limit the penetration of microwaves
      in the depth of the tissue maintaining the full efficacy of hyperthermia. The
      study was firstly performed by computer simulations of SAR distribution inside a
      flat homogeneous phantom, considering various thicknesses of the integrated water
      bolus. Simulations, validated by the measurements, were also used to evaluate the
      impedance matching. Further tests were performed on homogeneous agar phantom to
      simulate the temperature distribution in the biological tissue and to preliminary
      assess the possible modality and schedule of microwave hyperthermia delivery. The
      in vivo experiments showed the evidence of direct microwave-induced heating and
      damage of the melanoma tissue in a range of penetration coherent both with
      computer simulations and phantom studies. The described approach appears
      perspective for designing limited-microwave-delivery applicators tailored for
      treatments of human superficial tumors and pre-tumoral lesions.

PMID- 20033790
TI  - BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture
      conditions on laminin.
AB  - Because mouse embryonic stem cells (mESCs) do not contribute to the formation of
      extraembryonic placenta when they are injected into blastocysts, it is believed
      that mESCs do not differentiate into trophoblast whereas human embryonic stem
      cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic
      protein 4 (BMP4) in vitro. To test whether mESCs have the potential to
      differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a
      defined monolayer culture condition. The expression of trophoblast-specific
      transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was
      specifically upregulated in the BMP4-treated differentiated cells, and these
      cells expressed trophoblast markers. These results suggest that BMP4 treatment in
      defined culture conditions enabled mESCs to differentiate into trophoblast. This
      differentiation was inhibited by serum or leukemia inhibitory factor, which are
      generally used for mESC culture. In addition, we studied the mechanism underlying
      BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4
      activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a
      crucial role in trophoblast differentiation, through the binding of Smad protein
      to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common
      molecular mechanism underlying hESC and mESC differentiation into trophoblast.

PMID- 20033792
TI  - Medium for development of bee cell cultures (Apis mellifera: Hymenoptera:
      Apidae).
AB  - A media for the production of cell cultures from hymenopteran species such as
      honey bee, Apis mellifera L. (Hymenoptera: Apidae) was developed. Multiple bee
      cell cultures were produced when using bee larvae and pupae as starting material
      and modified Hert-Hunter 70 media. Cell culture systems for bees solves an
      impasse that has hindered efforts to isolate and screen pathogens which may be
      influencing or causing colony collapse disorder of bees. Multiple life stages of
      maturing larvae to early pupae were used to successfully establish cell cultures
      from the tissues of the head, thorax, and abdomen. Multiple cell types were
      observed which included free-floating suspensions, fibroblast-like, and epithelia
      like monolayers. The final culture medium, WH2, was originally developed for
      hemipterans, Asian citrus psyllid, Diaphorina citri, and leafhopper, Homalodisca
      vitripennis cell cultures but has been shown to work for a diverse range of
      insect species such as bees. Bee cell cultures had various doubling times at 21
      23 degrees C ranging from 9-15 d. Deformed wing virus was detected in the primary
      explanted tissues, which tested negative by rt-PCR for Israeli acute paralysis
      virus (IAPV), Kashmir bee virus, acute bee paralysis virus, and black queen cell
      virus. Culture inoculation with IAPV from an isolate from Florida field samples,
      was detectable in cell cultures after two subcultures. Cell culture from
      hymenoptera species, such as bees, greatly advances the approaches available to
      the field of study on colony collapse disorders.

PMID- 20033791
TI  - Newly established cell lines from mouse oral epithelium regenerate teeth when
      combined with dental mesenchyme.
AB  - The present study attempted to examine whether clonal cell lines of the oral
      epithelium can differentiate into ameloblasts and regenerate tooth when combined
      with dental germ mesenchyme. Clonal cell lines with a distinct morphology were
      established from the oral epithelium of p53-deficient fetal mice at embryonic day
      18 (E18). The strain of mouse is shown to be a useful source for establishing
      clonal and immortalized cell lines from various tissues and at various stages of
      development. Tooth morphogenesis is almost completed and the oral epithelium is
      segregated from the dental epithelium at E18. In RT-PCR analysis of cell lines,
      mucosal epithelial markers (cytokeratin 14) were detected, but ameloblast markers
      such as amelogenin and ameloblastin were not detected when cells were cultured on
      plastic dish. They formed stratified epithelia and expressed a specific
      differentiation marker (CK13) in the upper layer when cultured on feeder layer or
      on collagen gel for 1-3 wk, demonstrating that they are of oral mucosa origin.
      Next, bioengineered tooth germs were prepared with cell lines and fetal molar
      mesenchymal tissues and implanted under kidney capsule for 2-3 wk. Five among six
      cell lines regenerated calcified structures as seen in natural tooth. Our results
      indicate that some oral epithelial cells at E18 possess the capability to
      differentiate into ameloblasts. Furthermore, cell lines established in the
      present study are useful models to study processes in tooth organogenesis and
      tooth regeneration.

PMID- 20033793
TI  - Analysis of the relationship between leukemia mortality and soil trace elements
      using chemometrics.
AB  - The relationship between the mortality of leukemia and the contents of trace
      elements in the soils of 29 regions of China was investigated. A total of 27
      elements were determined for each region. Considering that an efficient variable
      selection can be highly beneficial both to improve the predictive ability of the
      model and to greatly reduce its complexity, genetic algorithm-partial least
      squares was used to screen out 13 qualified elements. As a result, only 13
      elements, i.e., As, Hg, Mn, Sr, Ba, Cu, Ti, Co, K, Ca, Rb, Zn, and Mg, were
      picked out and, a partial least squares model with three latent variables was
      obtained, whose prediction exhibited a correlative coefficient of 0.874 with
      actual mortality. Especially, it showed a high negative correlation between the
      content of soil As and the mortality of leukemia. Such a fact can be explained by
      the apoptotic effect of cancerous cells by trace-amount arsenic trioxide.
      Furthermore, according to whether the mortality was larger than two out of
      100,000 (2 * 10-5), all the 29 regions were divided into 21 high-mortality
      regions and eight low-mortality regions and were assigned the label -1 or 1,
      respectively. Using the same 13 elements, a Fisher's discriminant analysis model
      was developed, which can successfully discriminate low- and high-mortality
      groups.

PMID- 20033794
TI  - Association between EGF promoter polymorphisms and cancer risk: a meta-analysis.
AB  - EGF promoter polymorphisms are observed to modulate EGF levels and thought to
      have effect on susceptibility to various carcinomas but the results are
      inconsistent. In this meta-analysis, we assessed published studies of the
      association between three EGF polymorphisms and cancer risk from 21 studies with
      14,609 subjects for EGF G61A, from two studies with 2,535 subjects for G-1380A
      and A-1744G, respectively. For EGF G61A, the contrast of homozygote (OR=0.80, 95%
      CI=0.65-0.98), allele (OR=0.90, 95% CI=0.81-0.99) and dominant model (OR=0.86,
      95% CI=0.74-0.99) produced significant association among 21 studies with
      relatively large heterogeneity (Pheterogeneity<0.001). Through the stratified
      analysis, heterogeneity decreased significantly. In the stratified analysis by
      racial descent, the significant risks were found among Asians for homozygote
      contrast (OR=0.83, 95% CI=0.69-0.99, Pheterogeneity=0.506) and Americans for the
      contrast of homozygote (OR=0.50, 95% CI=0.30-0.84, Pheterogeneity=0.051), allele
      (OR=0.70, 95% CI=0.51-0.96, Pheterogeneity=0.008) and dominant model (OR=0.57,
      95% CI=0.42-0.77, Pheterogeneity=0.28). No significant associations were found in
      all Caucasians genetic models. In the subgroup analyses by cancer types, for
      gastric cancer and esophageal cancer significant associations were found in all
      genetic models without heterogeneity. Significant risk was also found in the
      contrast of homozygote (OR=0.41, 95% CI=0.20-0.81, Pheterogeneity=0.184) and
      recessive model (OR=0.53, 95% CI=0.33-0.85, Pheterogeneity=0.384) for hepatoma
      and recessive model (OR=0.72, 95% CI=0.53-0.99, Pheterogeneity=0.474) for glioma.
      For EGF G-1380A and A-1744G, no significant associations were found in all
      genetic models. This meta-analysis suggests that the EGF G61A polymorphism most
      likely contributes to decreased susceptibility to cancers among Asians and
      Americans, and A allele may be a protective factor for gastric cancer, esophageal
      cancer, hepatoma and glioma. Both EGF G-1380A and A-1744G is marginally
      associated with cancer susceptibility.

PMID- 20033795
TI  - Reading fluency: implications for the assessment of children with reading
      disabilities.
AB  - The current investigation explored the diagnostic utility of reading fluency
      measures in the identification of children with reading disabilities.
      Participants were 50 children referred to a university-based clinic because of
      suspected reading problems and/or a prior diagnosis of dyslexia, where children
      completed a battery of standardized intellectual, reading achievement, and
      processing measures. Within this clinical sample, a group of children were
      identified that exhibited specific deficits in their reading fluency skills with
      concurrent deficits in rapid naming speed and reading comprehension. This group
      of children would not have been identified as having a reading disability
      according to assessment of single word reading skills alone, suggesting that it
      is essential to assess reading fluency in addition to word reading because
      failure to do so may result in the under-identification of children with reading
      disabilities.

PMID- 20033796
TI  - Diagnosing hemodynamic instability in the comatose patient.

PMID- 20033797
TI  - Neuroimaging of autism.
AB  - Neuroimaging studies done by means of magnetic resonance imaging (MRI) have
      provided important insights into the neurobiological basis for autism. The aim of
      this article is to review the current state of knowledge regarding brain
      abnormalities in autism. Results of structural MRI studies dealing with total
      brain volume, the volume of the cerebellum, caudate nucleus, thalamus, amygdala
      and the area of the corpus callosum are summarised. In the past 5 years also new
      MRI applications as functional MRI and diffusion tensor imaging brought
      considerable new insights in the pathophysiological mechanisms of autism.
      Dysfunctional activation in key areas of verbal and non-verbal communication,
      social interaction, and executive functions are revised. Finally, we also discuss
      white matter alterations in important communication pathways in the brain of
      autistic patients.

PMID- 20033798
TI  - Influence of carotid artery stenting on cognitive function.
AB  - INTRODUCTION: There have only been a few studies on cognitive changes in patients
      with carotid occlusive disease, and the results of these show major discrepancies
      in the extent to which treatment affects neuropsychological function. We sought
      to clarify these discrepancies by evaluating the effects of carotid artery
      stenting (CAS) on the cognitive function. METHODS: Forty-one asymptomatic CAS
      patients were administered a test battery of neuropsychological tests measuring
      cognitive speed and memory function before and 3 months after the procedure. A
      control group was also evaluated. To test for thromboembolic lesions, diffusion
      weighted imaging was used. RESULTS: CAS led to a significant increase in
      cognitive speed (p<0.001) but did not afford any change in memory function. This
      was regardless of the degree or side of stenosis or patient age or gender.
      CONCLUSION: CAS significantly improved functions that involve cognitive speed.
      Earlier studies did not differentiate between speed and memory tests and thus
      might have missed these changes. Further studies correlating changes in brain
      perfusion with increase in cognitive speed are needed.

PMID- 20033799
TI  - Successful post-remission therapy with a combination of all-trans retinoic acid
      and arsenic trioxide in an elderly Japanese patient newly diagnosed with acute
      promyelocytic leukemia.

PMID- 20033800
TI  - Successful unrelated bone marrow transplantation for a human immunodeficiency
      virus type-1-seropositive acute myelogenous leukemia patient following HAART.
AB  - The availability of highly active anti-retroviral therapy (HAART) has greatly
      improved the outcome of human immunodeficiency virus type-1 (HIV-1) infection and
      disease. We report here on a case of an HIV-1-seropositive patient with acute
      myelogenous leukemia who underwent a successful allogeneic unrelated bone marrow
      transplantation following HAART. A 40-year-old Japanese HIV-seropositive man
      underwent allogeneic unrelated bone marrow transplantation using a myeloablative
      pretransplant-conditioning regimen. Neutrophil engraftment occurred on day +18,
      and donor chimerism was achieved on day +27. During pre- and post-
      transplantation, the HAART was not interrupted. Over 1 year after
      transplantation, the patient is alive and in continuous complete remission with
      undetectable levels of HIV-1 RNA. HAART can lead to a successful hematopoietic
      stem cell transplantation without severe opportunistic infections.

PMID- 20033801
TI  - The use of parallel pre-contoured plates in the treatment of A and C fractures of
      the distal humerus.
AB  - The purpose of this study was to retrospectively evaluate the clinical and
      radiological results of fixation with parallel pre-contoured plates in intra
      articular and extra-articular distal humerus fractures. We retrospectively
      evaluate seven cases of type A and six cases of type C fracture treated with the
      Mayo Clinic Congruent Elbow Plate system (Acumed, Hillsboro, Oregon) after a mean
      follow-up of 14.8 and 21.3 months, respectively. Mayo Elbow Performance Score
      (MEPS) was utilized for functional evaluation. Mean MEPS was (92.86 +/- 16.8) in
      the first group showing 6 excellent and one poor result, while (94.17 +/- 12)
      showing five excellent and one fair in the second group, showing no significant
      difference between the two groups (P = 0.87). The mean active motion recovered
      postoperatively was 120 degrees (+/-34.5 degrees) in type A fractures and 113
      degrees (+/-14.7 degrees) in type C fractures, and there was no significant
      difference (P = 0.67). Complications occurred in 6 of the 13 patients analysed at
      follow-up (3 radial neuropathy, one ulnar neuropathy, one screw mobilization and
      one heterotopic ossification). The fractures healed in every patient, and no
      synthesis failed. The parallel plate system has proved to be extremely useful in
      the treatment of intra-articular and extra-articular distal humerus fractures.
      The pre-contoured geometry allows easier reduction and stabilization of complex
      fractures. The higher stability achieved permits early mobilization, thus
      obtaining a higher percentage of excellent results.

PMID- 20033802
TI  - Evidence for neuroendocrine function of a unique splicing form of TCF7L2 in human
      brain, islets and gut.
AB  - AIMS/HYPOTHESIS: Variants in the TCF7L2 gene remain the strongest genetic
      associations with increased risk of type 2 diabetes. Recently, we identified a
      unique splicing form of TCF7L2 expressed in pancreatic islets, pancreas and colon
      and detected by assay 'ex13-13b'. The expression of ex13-13b strongly correlated
      with proinsulin in glucose-stimulated pancreatic islets, suggesting a potential
      role for this form in the development of type 2 diabetes. The goal of this study
      was to further characterise this unique TCF7L2 splicing form in human tissues.
      METHODS: We used a panel of 34 human tissues and 80 human cell lines to measure
      the expression of assay ex13-13b with use of quantitative RT-PCR. RESULTS: The
      highest expression of assay ex13-13b was detected in several areas of the brain
      (hypothalamus/thalamus, occipital lobe) and in neuronal cell line SHS5Y5. Low
      expression was confirmed in pancreatic islets, small intestine, pancreas and
      colon, while no expression was detected in other human tissues and cell lines.
      The expression of assay ex13-13b correlated with the gene for cocaine- and
      amphetamine-regulated transcript (CART, also known as CARTPT) in a panel of human
      tissues (n = 12, r = 0.85, p = 0.00046), pancreatic islets (n = 23, r = 0.62, p =
      0.0016) and colon (n = 98, r = 0.54, p < 0.0001). CONCLUSIONS/INTERPRETATION: The
      significant correlation between expression of a unique splicing form of TCF7L2,
      named here TCF7L2-NE, and CART, the gene for an anorexigenic neurohormone
      expressed in the central and peripheral nervous system, suggests that these
      transcripts may share neuroendocrine functions important for brain, gut and
      pancreatic islets.

PMID- 20033804
TI  - [Neurogenic foot deformities].
AB  - There is a multitude of neurological diseases which may lead to neuro-orthopaedic
      problems and subsequently to neurogenic foot deformities. For this reason the
      diagnostician will be consistently surprised that there is a great multitude of
      different foot abnormalities and that not only the typical spastic talipes
      equines dominates. Of particular significance here is that these deformities
      almost always develop progressively, whereas most diseases persist per se,
      cerebral palsy being a typical case in point. However, in MMC (myelomeningocele)
      patients, there is also the danger of a worsening of the basic problem in the
      case of tethered cord syndrome. Unlike congenital talipes equinovarus, neuro
      orthopaedic talipes equinovarus often shows over- or undercorrection
      postoperatively due to a shift in muscle imbalance. It is important, therefore,
      that the basis of conservative therapy include regular physiotherapy and orthoses
      during the day and, if necessary, at night. Botulinum toxin has been established
      as an additional measure for spasticity; however, this cannot always prevent
      surgical intervention, but is able to delay this to a better point in the
      development of the child/patient. The present article describes the diversity of
      neurological deformities and presents conservative as well as surgical
      therapeutic approaches.

PMID- 20033803
TI  - Effect of forkhead box O1 (FOXO1) on beta cell development in the human fetal
      pancreas.
AB  - AIMS/HYPOTHESIS: Recent studies have demonstrated that in adult murine beta cells
      the forkhead box O1 (FOXO1) transcription factor regulates proliferation and
      stress resistance. However, the role of FOXO1 during pancreatic development
      remains largely unknown. The present study aimed to characterise the expression
      of the FOXO1 transcription factor in the early to mid-gestation human fetal
      pancreas and to understand its role in islet cell development. METHODS: Human (8
      21 week fetal age) pancreases were examined using immunohistological,
      quantitative RT-PCR and western blotting. Isolated human (18-21 week) fetal islet
      epithelial cell clusters were treated with insulin or glucose, or transfected
      with FOXO1 small interfering RNA (siRNA). RESULTS: Nuclear and cytoplasmic FOXO1
      were widely produced during human fetal endocrine pancreatic development, co
      localising in cells with the transcription factors pancreatic and duodenal
      homeobox 1 (PDX-1) and neurogenin 3 (NGN3) as well as cytokeratin 19 (CK19),
      insulin and glucagon. Treatment with exogenous insulin (50 nmol/l) induced the
      nuclear exclusion of FOXO1 in both cytokeratin 19 (CK19)(+) (p < 0.01) and
      insulin(+) cells (p < 0.05) in parallel with increased phospho-Akt (p < 0.05)
      production. siRNA knockdown of FOXO1 significantly increased the number of
      NGN3(+) (p < 0.01) and NK6 homeobox 1 (NKX6-1)(+) (p < 0.05) cells in parallel
      with increases in insulin gene expression (p < 0.03) and C-peptide(+) cells (p <
      0.05) and reduced levels of hairy and enhancer of split 1 (HES1) (p < 0.01).
      CONCLUSIONS/INTERPRETATION: Our results indicate that FOXO1 may negatively
      regulate beta cell differentiation in the human fetal pancreas by controlling
      critical transcription factors, including NGN3 and NKX6-1. These data suggest
      that the manipulation of FOXO1 levels may be a useful tool for improving cell
      based strategies for the treatment of diabetes.

PMID- 20033805
TI  - In vitro evaluation of selenium genotoxic, cytotoxic, and protective effects: a
      review.
AB  - Selenium is an oligoelement with essential biological functions. Diet is the most
      important selenium source, and intake of this element depends on its
      concentration in food and amount of food consumed. Among the essential human
      micronutrients, selenium is peculiar due to its beneficial physiological activity
      and toxicity. It may have anticarcinogenic effects at low concentrations, whereas
      at concentrations higher than those necessary for nutrition, it can be genotoxic
      and carcinogenic. Because of that, selenium is probably the most widely
      investigated of all the oligonutrients. In the last decades, there has been
      increasing interest in several nutritional Se compounds because of their
      environmental, biological, and toxicological properties, particularly for their
      cancer- and disease-preventing activities. This article gives an overview of the
      results of in vitro studies on mutagenicity, genotoxicity, cytotoxicity, and DNA
      repair conducted within the last decades with different organic and inorganic
      selenium compounds. Results from these studies provide a better knowledge on the
      selenium activity and help to elucidate the reasons underlying its duality in
      order to regulate its correct use in nutrition and clinic.

PMID- 20033806
TI  - Functional characterization of human cytochrome P4502E1 allelic variants: in
      vitro metabolism of benzene and toluene by recombinant enzymes expressed in yeast
      cells.
AB  - Benzene and toluene are common organic solvents currently in worldwide industrial
      usage, which are metabolized mainly by hepatic cytochrome P450 2E1 (CYP2E1) in
      humans. Genetic polymorphism of CYP2E1 in 5'-flanking and coding regions has been
      found previously in Caucasian and Chinese populations. In this study, the effects
      of CYP2E1 alleles causing amino acid substitutions (CYP2E1*2, CYP2E1*3 and
      CYP2E1*4; wild-type, CYP2E1.1A) on benzene hydroxylation and toluene
      methylhydroxylation were studied using recombinant CYP2E1 enzymes of wild-type
      (CYP2E1.1) and variants (CYP2E1.2 having Arg76His, CYP2E1.3 having Val389Ile and
      CYP2E1.4 having Val179Ile) expressed in yeast cells. The K (m), V (max) and CL
      (int) values of CYP2E1.1 were 10.1 mM, 9.38 pmol/min/pmol CYP and 0.99
      nL/min/pmol CYP for benzene hydroxylation, and 3.97 mM, 19.9 pmol/min/pmol CYP
      and 5.26 nL/min/pmol CYP for toluene methylhydroxylation, respectively. The K
      (m), V (max) and CL (int) values for benzene and toluene metabolism of CYP2E1.2,
      CYP2E1.3 and CYP2E1.4 were comparable to those of wild-type CYP2E1. These
      findings may mean that the polymorphic alleles of CYP2E1 causing amino acid
      substitutions are not directly associated with the metabolic activation of
      benzene and toluene. The information gained in this study should help to identify
      the variations in the toxicity of environmental pollutants.

PMID- 20033807
TI  - Hospital cost analysis of management of patients with renal colic in the
      emergency department.
AB  - Acute severe colicky pain in the flank region is termed as renal colic (RC),
      which is commonly diagnosed and treated in the emergency department (ED). The
      present study is designed to investigate the hospital costs of patients with RC
      admitted to the ED and factors affecting the figures. Retrospective analysis
      includes all patients diagnosed with RC following physical examination and X-ray,
      ultrasound, computed tomography together with laboratory investigations in the
      university-based ED between February 2007 and February 2009. The study included
      574 patients eligible for the predefined criteria. Mean total hospital cost in
      patients admitted to the ED due to RC was calculated to be 55.77 Euro. The
      greatest contribution to the total cost was made by radiological investigations
      in the ED (40.5%) followed by treatment costs (19.7%). Size and location of the
      stone and stay times in the ED were the independent variables affecting the
      costs. The costs were higher as the stones were bigger and as they were more
      distal in the ureter. Renal stones were associated with the lowest hospital
      costs. Radiological investigations are the greatest contributors in the ED costs
      in patients with RC. Effective measures need to be undertaken to reduce resultant
      costs. Preventive measures as well as diagnostic and therapeutic procedures
      should be standardized in the ED in accordance with technological advances and
      also cost-effectiveness when appropriate.

PMID- 20033808
TI  - Post-surgical follow-up of colorectal cancer: role of contrast-enhanced CT
      colonography.
AB  - AIM: To evaluate the role of CT colonography (CTC) in the follow-up of patients
      having received partial colectomy for colorectal cancer. METHODS AND MATERIALS:
      CTC was performed in 72 subjects with history of partial colectomy for colorectal
      cancer. Colectomy had been performed in the right colon (n = 18), descending
      colon (n = 15), sigmoid colon (n = 21), and rectum (n = 18). Patients underwent
      CTC following incomplete conventional colonoscopy due to intolerance to endoscope
      insertion or luminal stenosis. In 70 cases pneumocolon was obtained through a
      rectal tube, and in 2 cases through a cutaneous anastomosis. CTC datasets were
      analyzed in combined 2D and 3D mode. All patients in whom CTC was suggestive for
      or raised the suspicion of disease recurrence underwent colonoscopy in sedation
      for confirmation of CTC findings. RESULTS: CTC detected 7 cases of anastomotic
      stenosis. In 6/7 patients the stenosis was located in the sigmoid colon and in
      1/7 patients at the level of the ileo-colic junction in the transverse colon. Out
      of these cases, four were fibrotic and three were neoplastic stenoses. In none of
      these cases was the CT appearance of the stenoses specific for disease
      recurrence, and conventional colonoscopy together with biopsy was necessary in
      order to characterize such findings. However, sensitivity of CTC in detecting
      anastomotic stenosis was 100% (7/7). One colonic mass (5 cm largest diameter) was
      detected in one case at the level of the proximal transverse colon in a patient
      with left colectomy performed 2 years before. The study of the residual colon
      showed 3 polyps in three patients (8, 6, and 5 mm, respectively). All CT findings
      were confirmed and characterized by conventional colonoscopy. In all cases the
      residual colon was entirely visualized by CTC with a completion rate of 100%.
      CONCLUSIONS: CTC is a feasible and minimally invasive method for full exploration
      of the colon after surgical resection allowing detection of cancer recurrence,
      metachronous disease, and distant metastases in one single study, and represents
      a valid alternative to conventional colonoscopy in this patient population.

PMID- 20033809
TI  - Biodistribution of humanized anti-VEGF monoclonal antibody/bevacizumab on
      peritoneal metastatic models with subcutaneous xenograft of gastric cancer in
      mice.
AB  - PURPOSE: Vascular endothelial growth factor (VEGF) is correlated with peritoneal
      metastasis of gastric cancer, increasing vascular permeability accompanied by
      accumulation of ascites. The aim of the current study is to investigate the
      biodistribution of bevacizumab in a peritoneal metastatic model of gastric cancer
      and to clarify which is more suited to treatment of peritoneal metastasis,
      systemic or regional therapy. METHODS: A highly peritoneal-seeding cell line of
      gastric cancer, OCUM-2MD3, which exhibited high production and release of VEGF
      was used in this study. The biodistribution of bevacizumab was investigated using
      peritoneal metastatic models together with subcutaneous xenografts, and (125)I
      radiolabelled bevacizumab was administrated to these models subcutaneously (s.c.)
      or intraperitoneally (i.p.), respectively. In addition, the anti-tumor response
      of bevacizumab and paclitaxel was assessed as single agents or in combination
      using peritoneal metastatic models. RESULTS: In the analysis of biodistribution,
      (125)I-bevacizumab administrated i.p. indicated low peritoneal clearance. On the
      other hand, s.c. administration of (125)I-bevacizumab showed preferential
      accumulation in subcutaneous tumors and peritoneal nodules, with a high blood
      concentration. In peritoneal metastatic models, the effects of bevacizumab were
      found for both the growth inhibition of peritoneal nodules (P < 0.01) and the
      reduction of ascites (P < 0.05). These effects were more prominent by s.c.
      administration compared with i.p. administration and were increased in
      combination with i.p. paclitaxel. CONCLUSION: Bevacizumab should be administrated
      systemically compared to regionally, and the combination with i.p. paclitaxel has
      a potential to be useful for patients with peritoneal metastasis of gastric
      cancer.

PMID- 20033810
TI  - Randomized controlled phase II comparison study of concurrent chemoradiotherapy
      with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5
      fluorouracil, methotrexate and leucovorin in patients with locally advanced
      squamous cell carcinoma of the head and neck.
AB  - We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP),
      and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and
      leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of
      the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of
      100 patients were enrolled. The TPF group received CCRT with the TPF regimen
      [docetaxel (50 mg/m(2): day 1), CDDP (60 mg/m(2): day 4), and continuous 5-FU
      infusion (600 mg/m(2)/day: days 1-5)]. In the PFML group, patients received CCRT
      with the PFML regimen [CDDP (60 mg/m(2): day 4)], continuous 5-FU infusion (600
      mg/m(2)/day: days 1-5), methotrexate (30 mg/m(2): day 1) and leucovorin (20
      mg/m(2)/day: days 1-5)]. Both groups received 2 cycles of chemotherapy during
      definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray.
      The overall response rates after CCRT were 98 with 90% of a pathologically
      complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For
      grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the
      TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or
      PMFL for advanced SCCHN was tolerable and produced excellent survival rates.

PMID- 20033811
TI  - Corchorusin-D, a saikosaponin-like compound isolated from Corchorus acutangulus
      Lam., targets mitochondrial apoptotic pathways in leukemic cell lines (HL-60 and
      U937).
AB  - PURPOSE: The presence of triterpene saponins in Corchorus acutangulus Lam. has
      been reported. However, no studies concerning biological activity of the plant
      extracts have been done so far. In the present study, the anti-leukemic activity
      of the methanol extract of aerial parts (ME) of C. acutangulus has been
      investigated, and efforts have been made to identify the active ingredient
      responsible for this activity. METHODS: The anti-leukemic activity of ME, its
      fractions and corchorusin-D (COR-D), the active ingredient, was investigated in
      leukemic cell lines U937 and HL-60 using cell viability and MTT assays. The
      molecular pathways leading to the activity of COR-D were examined by confocal
      microscopy, flow-cytometry, caspase and Western blot assays. RESULTS: ME, its n
      butanolic fraction and COR-D inhibited cell growth and produced significant
      cytotoxicity in leukemic cell lines U937 and HL-60. COR-D produced apoptotic cell
      death via mitochondrial disfunction and was found to pursue the intrinsic pathway
      by inciting the release of apoptosis-inducing factors (AIFs) from mitochondria.
      COR-D-induced translocation of Bax from cytosol to mitochondria facilitating
      caspase-9 activation and up regulation of downstream pathways leading to caspase
      3 activation and PARP cleavage, which resulted in the subsequent accumulation of
      cells in the sub-G0 phase followed by DNA fragmentation. CONCLUSIONS: COR-D
      possesses significant anti-leukemic activity in U937 and HL-60 cell lines by
      acting on the mitochondrial apoptotic pathways. Since the necrotic body formation
      is low after COR-D treatment, the occurrence of inflammation in in vivo systems
      could be reduced, which represents a positive indication in view of therapeutic
      application.

PMID- 20033812
TI  - Clinical impact of microsatellite instability in colon cancer following adjuvant
      FOLFOX therapy.
AB  - PURPOSE: Colon cancer with DNA mismatch repair (MMR) defects reveals
      indistinguishable clinical and pathologic aspects, including better prognosis and
      reduced response to 5-fluorouracil (5-FU)-based chemotherapy. There has been no
      consensus for p53 as a prognostic marker in colorectal cancer. This study
      investigated the clinical implication of MSI-H/MMR-D and p53 expression in R0
      resected colon cancer patients who received adjuvant oxaliplatin/5-FU/leucovorin
      (FOLFOX) therapy. EXPERIMENTAL DESIGN: We analyzed 135 patients, who had been
      treated by adjuvant chemotherapy containing 5-FU and oxaliplatin (FOLFOX) after
      curative resection (R0) for colon adenocarcinoma between May 2004 and November
      2007. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by
      immunohistochemistry (IHC) in surgically resected tumor specimens. MSI was
      analyzed by polymerase chain reaction (PCR) amplification using fluorescent dye
      labeled primers specific for microsatellite loci. Tumors with MMR defects were
      defined as those demonstrating loss of MMR protein expression (MMR-D) and/or
      microsatellite instability high (MSI-H) genotype. Expression patterns of p53 were
      determined in a semiquantitative manner by light microscopy. RESULTS: There were
      13 (9.6%) patients with stage II, 108 (80%) with stage III, and 14 (10.4%) with
      stage IV. Fourteen patients with stage IV (10.3%) had metastases to liver only,
      all of whom underwent complete metastasectomy for liver metastases. In total, 134
      tumor specimens were genotyped, 115 specimens were tested by IHC and 113 cases
      had both genotyping and IHC results available for analysis. Genotyping results
      demonstrated that 12 (9.0%) cases were MSI-H and 122 (91.0%) were MSI-L/S. By
      IHC, 11 (9.6%) patients were MMR-D and 104 (90.4%) were MMR-I. The methods were
      in agreement in 108 patients (94.7%). We assessed 114 patients for p53 expression
      by immunostaining. MMR status was not significantly associated with DFS (P =
      0.56) or OS (P = 0.61) in patients with colon cancer (n = 135) receiving adjuvant
      FOLFOX. According to p53 status, there was also no significant difference for DFS
      (P = 0.11) and OS (P = 0.94). For patients with genotyping/IHC agreement (n =
      108), there was no difference in DFS (P = 0.57) and OS (P = 0.98) between
      patients with MSI-H/MMR-D and MSI-L/S/MMR-I tumors. CONCLUSION: The MMR status or
      p53 positivity was not significantly associated with outcomes to FOLFOX as
      adjuvant chemotherapy in colon cancer patients with R0 resection. Adding
      oxaliplatin in adjuvant chemotherapy may overcome negative impact of 5-FU on
      colon cancers with MSI-H/MMR-D.

PMID- 20033813
TI  - Perioperative management of immunosuppression in rheumatic diseases--what to do?
AB  - To stop or not to stop immunosuppressive therapy in the perioperative setting
      puts the clinician to a challenge. The risk of potential wound infection with
      possible septic or even lethal consequences needs to be weighted against
      exacerbation of the rheumatic disease. However, exacerbation of autoimmune
      inflammatory activity needs to be treated with increasing immunosuppressive
      medication, thus leading to enhanced risk of local and systemic infection as
      well. Unfortunately, up to now there is no data from randomized, double-blind
      controlled clinical trials available on how to steer immunosuppressive therapy in
      the perioperative setting, making evidence-based recommendations difficult.
      Neither is there good evidence, if the risk of infectious complications under
      immunosuppressive therapy differs according to the type and localization of
      surgery performed. Finally, immunosuppressive co-medication, like glucocorticoid
      dosage, is not adequately addressed in the available studies, making
      interpretation of these studies even more problematic. Therefore, a decision has
      to be made on an individual basis. We discuss the available data on DMARD and
      biologics therapy in the perioperative setting and describe our own perioperative
      management with different DMARDs and biologics.

PMID- 20033816
TI  - [The clown doctor: an introduction].
AB  - In the literature, increasing numbers of practitioners have reported their
      experience using clown doctors in geriatric settings. The reports agree on the
      positive effects on persons with dementia and also on their caregivers. However,
      empirical studies on its effectiveness are rare. This article presents the field
      of activity of a clown doctor in geriatric settings as well as an overview of
      current scientific research on the topic and the effects on persons with dementia
      and nursing staff. It will be become clear that the clown doctor is a supporting
      therapeutic intervention. Through the clown representation, it is possible to
      obtain access to and interact with a person with dementia, thus, maintaining
      social contact of the patient with his/her environment. This effect leads to an
      increase of well-being and contributes to a reduction of problematic behavior. In
      addition to reduced workload and relief for the nursing staff, it has a positive
      effect on the working atmosphere.

PMID- 20033815
TI  - [Development of laughter and humour throughout the lifespan].
AB  - Humor and laughter are fundamental elements of human communication throughout the
      lifespan. The understanding of humor, humor production (e. g. joking) and
      functionality of humor (e. g. as a coping strategy) evolve in the course of a
      lifetime and are essentially determined by cognitive, verbal and social
      abilities. This review outlines the landmarks in the development of humor and
      laughter from early childhood to older age. In all stages of life, humor fulfils
      important functions; in the elderly, however, the function of humor as a coping
      mechanism gains in importance. Yet, humor processing, such as understanding of
      humor, humor production and emotional reactions to humor in the elderly, is an
      underresearched area.

PMID- 20033814
TI  - A novel mannose-based selection system for plant transformation using celery
      mannose-6-phosphate reductase gene.
AB  - To investigate its potential application as a selectable marker for plant
      transformation, the mannitol producing, celery mannose-6-phosphate reductase gene
      (M6PR) was transformed into Arabidopsis and tobacco using Agrobacterium
      tumefaciens-mediated transformation. Mannose-tolerance assays in transgenic
      materials revealed that the M6PR can act as a selectable marker gene in either a
      positive or a negative selection mode depending on the plant species. For mannose
      sensitive species, such as Arabidopsis, expression of M6PR enhanced mannose
      tolerance and provided a positive selection for transgenic seeds. On medium
      containing 2 g/L mannose, transgenic seeds germinated, whereas wild type (WT)
      seeds did not. For mannose-tolerant species, expression of M6PR increased mannose
      sensitivity in tobacco and enabled a negative selection for transgenic leaves and
      seeds. Mannose at 30 g/L blanched leaf explants from all 29 transgenic tobacco
      events with M6PR. In contrast, 30 g/L mannose did not inhibit shoot regeneration
      from leaf explants of WT or transgenic plants with either an antisense M6PR or a
      plasmid control. Similarly, mannose at 30 g/L inhibited seed germination of
      transgenic tobacco seeds with M6PR but not that of WT or transgenic tobacco with
      either the antisense M6PR or the plasmid control. Northern blot confirmed
      transcripts of the M6PR in transgenic tobacco, and accumulation of mannitol
      verified activity of the M6PR in tobacco leaves. Either positive or negative
      selection using the celery M6PR is versatile for plant transformation.
      Additionally, the celery M6PR is a potential target gene for improving salt
      tolerance in plants due to mannitol accumulation.

PMID- 20033817
TI  - A compound heterozygous mutation in the EDAR gene in a Spanish family with
      autosomal recessive hypohidrotic ectodermal dysplasia.
AB  - Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterised by
      sparse hair, lack of sweat glands and malformation of teeth. The X-linked form of
      the disease, caused by mutations in the EDA gene, represents the majority of HED
      cases. Autosomal forms result from mutations in either the EDAR or the EDARADD
      gene. The X-linked and autosomal forms are phenotypically indistinguishable. For
      the purpose of genetic counselling, it is, therefore, important to know which
      gene is involved. In this study, we ascertained a Spanish family demonstrating
      the autosomal recessive form of HED. Affected individuals in the family showed
      the characteristic features of HED, including fine and sparse scalp hair, sparse
      eyebrows and eyelashes, periorbital hyperpigmentation, prominent lips, hypodontia
      and conical teeth, reduced sweating, and dry and thin skin. Sequence analysis of
      the EDAR gene revealed a novel compound heterozygous mutation [c.52-2A>G;
      c.212G>A (p.Cys71Tyr)]. Our finding extends the body of evidence that supports
      the significance of the EDAR signalling pathway in the ectodermal morphogenesis.

PMID- 20033818
TI  - A method for detecting false bifurcations in dynamical systems: application to
      neural-field models.
AB  - In this article, we present a method for tracking changes in curvature of limit
      cycle solutions that arise due to inflection points. In keeping with previous
      literature, we term these changes false bifurcations, as they appear to be
      bifurcations when considering a Poincare section that is tangent to the solution,
      but in actual fact the deformation of the solution occurs smoothly as a parameter
      is varied. These types of solutions arise commonly in electroencephalogram models
      of absence seizures and correspond to the formation of spikes in these models.
      Tracking these transitions in parameter space allows regions to be defined
      corresponding to different types of spike and wave dynamics, that may be of use
      in clinical neuroscience as a means to classify different subtypes of the more
      general syndrome.

PMID- 20033819
TI  - Four-component power spectral density model of steady-state isometric force.
AB  - The aim of this study was to develop and evaluate a model based upon four
      identified characteristics of the power spectral density associated with
      isometric force at a range of constant force levels (5-95% maximum voluntary
      contraction). The characteristics modeled were: (1) a low-frequency resonant peak
      located at about 1 Hz; (2) a region of 1/f-like fractional Gaussian noise (fGn);
      (3) the resonant peak in the 8-12 Hz region on the PSD; and (4) Gaussian white
      noise resulting from a combination of neural as well as equipment noise. When
      superimposed, these components were used in a direct fit to the isometric force
      data to generate a linear predictor that resulted in residual values on the order
      of the white noise present in the original force time series.

PMID- 20033820
TI  - Attaining the canopy in dry and moist tropical forests: strong differences in
      tree growth trajectories reflect variation in growing conditions.
AB  - Availability of light and water differs between tropical moist and dry forests,
      with typically higher understorey light levels and lower water availability in
      the latter. Therefore, growth trajectories of juvenile trees--those that have not
      attained the canopy--are likely governed by temporal fluctuations in light
      availability in moist forests (suppressions and releases), and by spatial
      heterogeneity in water availability in dry forests. In this study, we compared
      juvenile growth trajectories of Cedrela odorata in a dry (Mexico) and a moist
      forest (Bolivia) using tree rings. We tested the following specific hypotheses:
      (1) moist forest juveniles show more and longer suppressions, and more and
      stronger releases; (2) moist forest juveniles exhibit wider variation in canopy
      accession pattern, i.e. the typical growth trajectory to the canopy; (3) growth
      variation among dry forest juveniles persists over longer time due to spatial
      heterogeneity in water availability. As expected, the proportion of suppressed
      juveniles was higher in moist than in dry forest (72 vs. 17%). Moist forest
      suppressions also lasted longer (9 vs. 5 years). The proportion of juveniles that
      experienced releases in moist forest (76%) was higher than in dry forest (41%),
      and releases in moist forests were much stronger. Trees in the moist forest also
      had a wider variation in canopy accession patterns compared to the dry forest.
      Our results also showed that growth variation among juvenile trees persisted over
      substantially longer periods of time in dry forest (>64 years) compared to moist
      forest (12 years), most probably because of larger persistent spatial variation
      in water availability. Our results suggest that periodic increases in light
      availability are more important for attaining the canopy in moist forests, and
      that spatial heterogeneity in water availability governs long-term tree growth in
      dry forests.

PMID- 20033821
TI  - High red deer density depresses body mass of roe deer fawns.
AB  - Many previous studies have pointed out that, when resources are limited, the
      potential for competition should be high among sympatric species that display
      overlaps in habitat and nutritional niches. However, reliable evidence of
      competition between red deer (Cervus elaphus) and roe deer (Capreolus capreolus)
      has not been yet reported for life history traits directly measuring performance
      such as body mass, reproduction, or survival. From long-term monitoring of deer
      populations in the reserve of La Petite Pierre (France), we measured the sex
      specific responses of roe deer fawn body mass to changes in red deer density
      after accounting for possible confounding effects of date of shooting, climatic
      conditions, and roe deer density. As expected under the hypothesis of
      competition, red deer density in a given year had a marked negative influence on
      body mass of roe deer fawns born the same year and the following year. Fawn mass
      of roe deer males and females responded in similar ways to changes in red deer
      density. Our study provides the first evidence of a negative response of roe deer
      performance to high red deer density.

PMID- 20033822
TI  - Observational evidence of risk-sensitive reproductive allocation in a long-lived
      mammal.
AB  - Organisms should adopt a risk-sensitive reproductive allocation when summer
      reproductive allocation competes with survival in the coming winter. This trade
      off is shown through autumn female body mass, which acts as an insurance against
      unpredictable winter environmental conditions. We tested this hypothesis on
      female reindeer in a population that has experienced a time period of dramatic
      increase in abundance. Environmental conditions during winter were fairly stable
      (with the exception of 1 year). We conclude that increased population abundance
      (perhaps in interaction with winter environmental conditions) could have
      represented a worsening of winter environmental conditions as both autumn
      offspring and spring female body mass decreased during the course of the study.
      Moreover, we found that the cost of reproduction was related to environmental
      conditions as: (1) autumn body mass was larger for barren than for lactating
      females, and this difference was temporally highly variable; (2) lactating
      females produced smaller offspring than barren ones in the following year; and
      (3) reproductive output (offspring size) decreased over time. We also found
      evidence of quality effects as lactating females had a higher reproductive
      success in the following year. In sum, a worsening of winter conditions lead to:
      (1) decreased reproductive output; (2) lowered autumn body mass for lactating
      females; and (3) increased body mass for barren females. Since females reduce
      their reproductive allocation as winter conditions becomes more severe, we
      conclude that reindeer have adopted a risk-sensitive reproductive allocation.

PMID- 20033823
TI  - The importance of biotic factors in predicting global change effects on
      decomposition of temperate forest leaf litter.
AB  - Increasing atmospheric CO(2) and temperature are predicted to alter litter
      decomposition via changes in litter chemistry and environmental conditions. The
      extent to which these predictions are influenced by biotic factors such as litter
      species composition or decomposer activity, and in particular how these different
      factors interact, is not well understood. In a 5-week laboratory experiment we
      compared the decomposition of leaf litter from four temperate tree species (Fagus
      sylvatica, Quercus petraea, Carpinus betulus and Tilia platyphyllos) in response
      to four interacting factors: elevated CO(2)-induced changes in litter quality, a
      3 degrees C warmer environment during decomposition, changes in litter species
      composition, and presence/absence of a litter-feeding millipede (Glomeris
      marginata). Elevated CO(2) and temperature had much weaker effects on
      decomposition than litter species composition and the presence of Glomeris. Mass
      loss of elevated CO(2)-grown leaf litter was reduced in Fagus and increased in
      Fagus/Tilia mixtures, but was not affected in any other leaf litter treatment.
      Warming increased litter mass loss in Carpinus and Tilia, but not in the other
      two litter species and in none of the mixtures. The CO(2)- and temperature
      related differences in decomposition disappeared completely when Glomeris was
      present. Overall, fauna activity stimulated litter mass loss, but to different
      degrees depending on litter species composition, with a particularly strong
      effect on Fagus/Tilia mixtures (+58%). Higher fauna-driven mass loss was not
      followed by higher C mineralization over the relatively short experimental
      period. Apart from a strong interaction between litter species composition and
      fauna, the tested factors had little or no interactive effects on decomposition.
      We conclude that if global change were to result in substantial shifts in plant
      community composition and macrofauna abundance in forest ecosystems, these
      interacting biotic factors could have greater impacts on decomposition and
      biogeochemical cycles than rising atmospheric CO(2) concentration and
      temperature.

PMID- 20033824
TI  - Mechanism of interdigestive migrating motor complex in conscious dogs.
AB  - BACKGROUND: The migrating motor complex (MMC) is well characterized by the
      appearance of gastrointestinal contractions in the interdigestive state. This
      study was designed to clarify the mechanisms of gastric MMC (G-MMC) and
      intestinal MMC (I-MMC) in conscious dogs. METHODS: Five strain gauge transducers
      were implanted on the stomach and intestine. To investigate the correlation
      between luminal 5-HT and phase III contractions, gastric and duodenal juices were
      collected during the MMC cycle. The 5-HT concentrations in gastric and duodenal
      juice were measured by HPLC. To investigate whether luminal 5-HT initiates MMC, 5
      HT (10(-8)-10(-6) M, 10 ml) was administered into the duodenum 20 min after
      gastric phase III. To investigate the involvement of 5-HT(3) or 5-HT(4) receptors
      in mediating G-MMC and I-MMC, 5-HT(3) antagonists (ondansetron) or 5-HT(4)
      antagonists (GR 125,487) were infused for 120 min. RESULTS: Luminal
      administration of 5-HT (10(-6) M) initiated duodenal phase II followed by G-MMC
      and I-MMC with a concomitant increased release of plasma motilin. The duodenal 5
      HT concentration was significantly increased during phase II (59 +/- 9 ng/ml) and
      phase III (251 +/- 21 ng/ml) compared to that of phase I (29 +/- 5 ng/ml). On the
      other hand, the 5-HT content in the stomach was not significantly changed
      throughout the MMC cycle. Intravenous infusion of motilin (0.3 microg/kg/h)
      increased the luminal 5-HT content and induced G-MMC and I-MMC. 5-HT(4)
      antagonists significantly inhibited both G-MMC and I-MMC, while 5-HT(3)
      antagonists inhibited only G-MMC. CONCLUSION: It is suggested that the MMC cycle
      is mediated by a positive feedback mechanism via the interaction between motilin
      and 5-HT.

PMID- 20033825
TI  - Evaluation of hemostasis with soft coagulation using endoscopic hemostatic
      forceps in comparison with metallic hemoclips for bleeding gastric ulcers: a
      prospective, randomized trial.
AB  - BACKGROUND: Endoscopic high-frequency soft coagulation, recently developed in
      Japan, is available for the management of gastric bleeding in cases of bleeding
      gastric ulcers and bleeding during endoscopic submucosal dissection. The aim of
      this study was to evaluate the efficacy of hemostasis with soft coagulation for
      bleeding gastric ulcers by comparing it with hemoclips in a prospective,
      randomized trial. METHODS: During the period of April 2006 to March 2008, 96
      patients that had gastric ulcers with bleeding or nonbleeding visible vessels
      were enrolled in this study. All of the 96 patients were randomly divided into
      two groups: endoscopic hemostasis with soft coagulation (Group I) or endoscopic
      hemoclipping (Group II). RESULTS: A total of 41 (85%) out of 48 patients in Group
      I and 38 (79%) out of 48 patients in Group II were successfully treated with soft
      coagulation or clipping alone, respectively. The endoscopic hemostasis rate for
      the initial modality in combination with another endoscopic procedure performed
      after the initial method was 98% in both groups. One patient in Group I (2%) and
      five patients in Group II (10%) experienced recurrent bleeding. The time required
      to achieve hemostasis was shorter in Group I compared with Group II (9.2 +/- 11.1
      vs. 13.6 +/- 9.4 min; P < 0.05). CONCLUSIONS: This study revealed that soft
      coagulation is as effective as hemoclipping for treating bleeding gastric ulcers.
      The time required to achieve hemostasis was shorter with the soft coagulation
      procedure.

PMID- 20033826
TI  - Relationship between lectin-like oxidized low-density lipoprotein receptor 1
      expression and preoperative echogenic findings of vulnerable carotid plaque.
AB  - PURPOSE: Lectin-like oxidized low-density lipoprotein 1 (LOX1) is an important
      cell surface receptor for the progression of atherosclerosis. Our purpose is to
      clarify the relationships of LOX1 and atherosclerotic factors for the
      vulnerability of carotid plaque and preoperative echogenic findings. METHODS: We
      examined LOX1 expression, matrix metalloproteinase (MMP)-2,9, and tissue
      inhibitor of MMP (TIMP)-2 by immunohistochemical analysis using carotid
      endarterectomy specimens obtained from 14 patients. Groups were divided into
      stable plaque group A and vulnerable plaque group B by preoperative echogenic
      findings of carotid plaques. Endothelial immunoreactivity was calculated, and the
      immunohistochemical findings were compared. RESULTS: LOX1 was remarkably
      expressed, especially in smooth muscle cells in vulnerable plaque and colocalized
      in MMP-9 positive cells and apoptotic cells. All LOX1, MMP-2,9, and TIMP2 were
      remarkably expressed in the subendothelial layer in group B compared with group
      A. The endothelial LOX1 index was 63.75 +/- 4.92 in group A and 83.0 +/- 5.02 in
      group B (p = 0.02). The endothelial MMP-2 index was 24.38 +/- 5.50 in group A and
      32.83 +/- 6.79 in group B (p = 0.01). The endothelial MMP-9 index was 46.13 +/-
      6.31 in group A and 59.17 +/- 2.14 in group B (p = 0.002). The endothelial TIMP-2
      index had no significant difference between two groups (p = 0.14). CONCLUSION:
      LOX-1 may play an important role in the progression of vulnerable carotid plaque
      and might regulate vulnerable plaque formation in cooperation with MMPs and TIMP
      2. Endothelial MMP-2 might suppress TIMP-2 activation in vulnerable plaques.

PMID- 20033827
TI  - Amino acid substitutions in an alpha-helical antimicrobial arachnid peptide
      affect its chemical properties and biological activity towards pathogenic
      bacteria but improves its therapeutic index.
AB  - Four variants of the highly hemolytic antimicrobial peptide Pin2 were chemically
      synthesized with the aim to investigate the role of the proline residue in this
      peptide, by replacing it with the motif glycine-valine-glycine [GVG], which was
      found to confer low hemolytic activity in a spider antimicrobial peptide. The
      proline residue in position 14 of Pin2 was substituted by [V], [GV], [VG] and
      [GVG]. Only the peptide variant with the proline substituted for [GVG] was less
      hemolytic compared to that of all other variants. The peptide variant [GVG] kept
      its antimicrobial activity in Muller-Hilton agar diffusion assays, whereas the
      other three variants were less effective. However, all Pin2 antimicrobial peptide
      variants, were active when challenged against a Gram-positive bacteria in Muller
      Hilton broth assays suggesting that chemical properties of the antimicrobial
      peptides such as hydrophobicity is an important indication for antimicrobial
      activity in semi-solid environments.

PMID- 20033828
TI  - Migraine and cerebral infarction in young people.
AB  - The objective of this study is to investigate relationship between migraine and
      cerebral infarction in young people. Patients aging 16-44 years, referred for
      stroke and age- and gender-matched controls were investigated for migraine
      following the International Headache Society criteria. Included people were 314
      strokes and 314 controls. Each group consisted of 150 men and 164 women. Of the
      105 persons with migraine (16.7%), 57 had migraine with aura (9.1%). In women,
      migraine with aura was related to stroke [35 women among strokes (21.3%) vs. 9
      among controls (5.5%), P < 0.0001], whereas migraine without aura was not. After
      multivariate analysis, migraine with aura remained independently associated with
      stroke together with hypertension, and the estro-progestinic utilization. In men,
      migraine was not associated with stroke. In conclusion, migraine with aura
      appears to be associated with ischemic stroke in young women, independently from
      other common risk factors.

PMID- 20033829
TI  - Role of matrix metalloproteinase-9 in apoptosis of hippocampal neurons in rats
      during early brain injury after subarachnoid hemorrhage.
AB  - This study investigated the possible involvement of matrix metalloproteinase 9
      (MMP-9) in early brain injury (EBI) of subarachnoid hemorrhage (SAH) in rats. MMP
      9 activities in hippocampus were examined at 6, 12, 24, 48 and 72 h after SAH.
      Laminin was detected by immunohistochemistry. Apoptosis of neurons in hippocampus
      was observed by TUNEL. Brain water content was also examined. MMP-9 activity and
      the number of apoptotic neurons increased from 12 to 72 h with a peak at 24 h.
      Laminin was found to decrease at 12 h, reached minimum at 24 h and began to
      increase from 48 h, which had a negative correlation with apoptotic neurons. The
      changes of brain water content were found to be coincidence with that of neuronal
      apoptosis. Our findings suggest that MMP-9 is probably involved in the
      pathophysiological events of EBI after SAH, through degrading laminin which leads
      to neuronal anoikis of hippocampus.

PMID- 20033830
TI  - Linking species concepts to natural product discovery in the post-genomic era.
AB  - A widely accepted species concept for bacteria has yet to be established. As a
      result, species designations are inconsistently applied and tied to what can be
      considered arbitrary metrics. Increasing access to DNA sequence data and clear
      evidence that bacterial genomes are dynamic entities that include large numbers
      of horizontally acquired genes have added a new level of insight to the ongoing
      species concept debate. Despite uncertainties over how to apply species concepts
      to bacteria, there is clear evidence that sequence-based approaches can be used
      to resolve cohesive groups that maintain the properties of species. This cohesion
      is clearly evidenced in the genus Salinispora, where three species have been
      discerned despite very close relationships based on 16S rRNA sequence analysis.
      The major phenotypic differences among the three species are associated with
      secondary metabolite production, which occurs in species-specific patterns. These
      patterns are maintained on a global basis and provide evidence that secondary
      metabolites have important ecological functions. These patterns also suggest that
      an effective strategy for natural product discovery is to target the cultivation
      of new Salinispora taxa. Alternatively, bioinformatic analyses of biosynthetic
      genes provide opportunities to predict secondary metabolite novelty and reduce
      the redundant isolation of well-known metabolites. Although much remains to be
      learned about the evolutionary relationships among bacteria and how fundamental
      units of diversity can be resolved, genus and species descriptions remain the
      most effective method of scientific communication.

PMID- 20033831
TI  - Homologous overexpression of a lipase from Burkholderia cepacia using the lambda
      Red recombinase system.
AB  - Red recombinase system of the lambda phage is widely used for recombination of
      short linear DNA fragments and genome. Using this system, we obtained T7 RNA
      polymerase (RNAP) substitution mutants in Burkholderia cepacia. To test the
      expression abilities of the T7 mutants, four different lipase expression vectors
      were transformed and the lipase activity of these recombinants was evaluated. Our
      results suggest that 500 nt homology between the unit and the genome is
      sufficient to generate mutations and this strategy enables the rapid
      establishment of mutant strains with efficiencies of 85%. After expression and
      purification, the highest purified lipase activity obtained was 3,990 U/l, nearly
      triple that of the wild-type organism.

PMID- 20033832
TI  - Molecular characterization of flavonol synthase from poplar and its application
      to the synthesis of 3-O-methylkaempferol.
AB  - Biosynthesis of flavonoid derivatives requires enzyme(s) having high reactivity
      as well as regioselectivity. We have synthesized 3-O-kaempferol from naringenin
      using two enzymes. The first reaction, in which naringenin is converted to
      kaempferol, is mediated by flavonol synthase (FLS). An FLS (PFLS) with strong
      catalytic activity was cloned and characterized from the genome sequence of the
      poplar (Populus deltoides). PFLS consists of a 1,008 bp ORF encoding a 38 kDa
      protein. PFLS was expressed in Escherichia coli with a glutathione-S-transferase
      (GST) tagging. The purified recombinant PFLS was characterized. Catalytically, it
      was more efficient than the previously characterized FLSs. A mixture of two E.
      coli transformants harboring either PFLS or ROMT9 (a kaempferol 3-O
      methyltransferase) converted naringenin into 3-O-methylkaempferol.

PMID- 20033833
TI  - Strain improvement of Lactobacillus lactis for D-lactic acid production.
AB  - Three mutants, isolated by repeated UV mutagenesis of Lactobacillus lactis NCIM
      2368, produced increased D: -lactic acid concentrations. These mutants were
      compared with the wild type using 100 g hydrolyzed cane sugar/l in the
      fermentation medium. One mutant, RM2-24, produced 81 g lactic acid/l which was
      over three times that of the wild type. The highest D: -lactic acid (110 g/l) in
      batch fermentation was obtained with 150 g cane sugar/l with a 73% lactic acid
      yield. The mutant utilizes cellobiose efficiently, converting it into D-lactic
      acid suggesting the presence of cellobiase. Thus, this strain could be used to
      obtain D-lactic acid from cellulosic materials that are pre-hydrolyzed with
      cellulase.

PMID- 20033834
TI  - A novel basic fibroblast growth factor delivery system fabricated with heparin
      incorporated fibrin-fibronectin matrices for repairing rat sciatic nerve
      disruptions.
AB  - Autologous nerve grafts are widely used in bridging critical gaps of peripheral
      nerves, but they remain associated with high morbidity of the donor site and lack
      of full recovery. As an alternative, we have focused on chitosan nerve conduits
      filled with a heparin-incorporated fibrin-fibronectin matrix serving as delivery
      systems for basic fibroblast growth factor (bFGF). The artificial nerve conduits
      were used for repairing sciatic nerve defects of 10 mm in adult rats. Three
      months post-operation, the conduction velocity recovery index (CVRI) and the
      muscle restoration rate (MRR) in animals of the experimental group were 32 +/-
      4.1 and 77.4 +/- 7.9%, respectively, which were significantly higher than those
      of the PBS control group (17.8 +/- 1.9 and 66.7 +/- 6.5%), and similar to those
      of the autograft group (38.4 +/- 3.9 and 81.3 +/- 7.8%). These results were also
      consistent with the densities of regenerated axons in the three groups, which
      were demonstrated by histomorphological analysis.

PMID- 20033835
TI  - Self-reported health, functional status and chronic disease in community dwelling
      older adults: untangling the role of demographics.
AB  - Self-reported health, a widely used measure of general health status in
      population studies, can be affected by certain demographic variables such as
      gender, race/ethnicity and education. This cross-sectional assessment of the
      current health status of older adult residents was conducted in an inner-city
      Houston neighborhood in May, 2007. A survey instrument, with questions on chronic
      disease prevalence, health limitations/functional status, self-reported
      subjective health status in addition to demographic data on households was
      administered to a systematic random sample of residents. Older adults (>60 years
      of age) were interviewed (weighted N = 127) at their homes by trained
      interviewers. The results indicated that these residents, with low literacy
      levels, low household income and a high prevalence of frequently reported chronic
      diseases (hypertension, diabetes and arthritis) also reported non-participation
      in community activities, volunteerism and activities centered on organized
      religion, thus, potentially placing them at risk for social isolation. Women
      reported poorer self-reported health and appeared to fare worse in all health
      limitation indicators and reported greater structural barriers in involvement
      with their community. Blacks reported worse health outcomes on all indicators
      than other sub-groups, an indication that skills training in chronic disease self
      management and in actively eliciting support from various sources may be
      beneficial for this group. Therefore, the use of self-reported health with a
      broad brush as an indicator of "true" population health status is not advisable.
      Sufficient consideration should be given to the racial/ethnic and gender
      differences and these should be accounted for.

PMID- 20033836
TI  - A role for community health promoters in tuberculosis control in the state of
      Chiapas, Mexico.
AB  - We conducted a qualitative study employing structured interviews with 38
      community health workers, known as health promoters, from twelve rural
      municipalities of Chiapas, Mexico in order to characterize their work and
      identify aspects of their services that would be applicable to community-based
      tuberculosis (TB) control programs. Health promoters self-identify as being of
      Mayan Indian ethnicity. Most are bilingual, speaking Spanish and one of four
      indigenous Mayan languages native to Chiapas. They volunteer 11 h each week to
      conduct clinical and public health work in their communities. Over half (53%)
      work with a botiquin, a medicine cabinet stocked with essential medicines. Fifty
      three percent identify TB as a major problem affecting the health of their
      communities, with one-fifth (21%) of promoters reporting experience caring for
      patients with known or suspected TB and 29% having attended to patients with
      hemoptysis. One-third of health promoters have access to antibiotics (32%) and
      one-half have experience with their administration; 55% complement their
      biomedical treatments with traditional Mayan medicinal plant therapies in caring
      for their patients. We describe how health promoters employ both traditional and
      allopathic medicine to treat the symptoms and diseases they encounter most
      frequently which include fever, diarrhea, and parasitic infections. We contend
      that given the complex sociopolitical climate in Chiapas and the state's
      unwavering TB epidemic and paucity of health care infrastructure in rural areas,
      efforts to implement comprehensive, community-based TB control would benefit from
      employing the services of health promoters.

PMID- 20033837
TI  - Colorectal cancer screening pilot program for underserved women in Cumberland
      County, Maine.
AB  - Over 800 Maine residents will be diagnosed with colorectal cancer (CRC) this
      year, and nearly 300 will die from the disease. While CRC screening can reduce
      these rates, it is only among insured populations that screening rates exceed
      50%. This project aimed to reduce barriers to, and increase rates of CRC
      screening among underinsured and uninsured women, ages 50 years and over,
      residing in Cumberland County, Maine. The existing network of the Maine Breast
      and Cervical Health Program (MBCHP) was used to reach the target population. A
      packet containing (1) an offer for no-cost fecal occult blood test (FOBT)
      screening and CRC-related educational materials, and (2) a stamped, addressed
      postcard specifying the woman's interest in these resources, was mailed to 300
      MBCHP enrollees residing in Cumberland County. Women requesting screening were
      contacted by phone to further determine eligibility. Ninety-three women (31%)
      requested FOBT kits and 29 of these women requested educational materials. Ten
      women were ineligible for screening because of previous colonoscopy. Fifty-two
      completed FOBT kits (63%) were returned; all were negative. An additional 42
      (14%) women requested educational materials only. To reduce the burden of CRC in
      Maine and nationally, disparate populations must be reached with efficient and
      effective screening services. Established networks are proven means for reaching
      uninsured and underinsured individuals with education, screening services, and
      necessary follow-up care. This project serves as a model for the future
      development of similar programs statewide and nationally.

PMID- 20033838
TI  - Complete genome sequence of an Argentinean isolate of Solenopsis invicta virus 3.
AB  - Solenopsis invicta virus 3 (SINV-3) is a recently described positive-strand RNA
      virus that infects the red imported fire ant, S. invicta. The genome of an
      Argentinean isolate of Solenopsis invicta virus 3 (SINV-3(ArgSF )) obtained from
      the Santa Fe region of Argentina was sequenced in entirety. Assembly of nine
      overlapping fragments yielded a consensus genome sequence 10,386 nucleotides
      long, excluding the poly(A) tail present on the 3' end (Genbank accession number
      GU017972). With the exception of the poly(A) tail, the genome length of SINV
      3(ArgSF ) was identical to the North American isolate (SINV-3(USDM )). The SINV
      3(ArgSF ) genome possessed three major open reading frames (ORFs) (comprised of
      >or=100 codons) in the sense orientation; SINV-3(USDM ) possessed only two. ORFs
      1 and 2 had identical start and stop genome positions for both isolates. Blastp
      analysis of the translated ORF 1 of SINV-3(ArgSF ) recognized conserved domains
      for helicase, protease, and RNA-dependent RNA polymerase. These domains and their
      corresponding positions were identical to those reported for SINV-3(USDM ). ORF
      2a, unique to the SINV-3(ArgSF ) genome, was also found in frame 2 and had a
      canonical start codon located at nucleotide position 8,351 and a stop codon
      ending at position 8,827. Blastp analysis of the translated amino acid sequence
      of ORF 2a revealed no significant similarity in the Genbank database. The two
      SINV-3 isolates exhibited 96.2% nucleotide sequence identity across the entire
      genome. The amino acid sequences of ORFs 1 and 2 exhibited higher identities
      (99.0 and 98.2%, respectively) than the corresponding nucleotide regions within
      the genome. These data indicated that the nucleotide differences between the SINV
      3 isolates were largely synonymous. This observation was corroborated by codon
      substitution rate analysis. Thus, the majority of the SINV-3 codon changes were
      silent in the two polyproteins, indicating purifying selection pressure on the
      viral genome.

PMID- 20033839
TI  - Genetic diversity of Hungarian Maize dwarf mosaic virus isolates.
AB  - The genetic diversity of the coat-protein (CP) region and the untranslated C
      terminal region (3'UTR) of Maize dwarf mosaic virus (MDMV) was analyzed to
      evaluate the variability between isolates (inter-isolate sequence diversity). The
      results of inter-isolate sequence diversity analysis showed that the diversity of
      the MDMV CP gene is fairly high (p-distance: up to 0.136). During sequence
      analysis, a 13 amino-acid residue insertion and an 8 amino-acid residue deletion
      were found within the N-terminal region of the CP gene. The phylogenetic analysis
      showed that-unlike other potyvirus species in this subgroup-the MDMV isolates
      could not be distinguished on the basis of their host plants or geographic
      origins.

PMID- 20033840
TI  - Decreased GABAA receptors functional regulation in the cerebral cortex and
      brainstem of hypoxic neonatal rats: effect of glucose and oxygen supplementation.
AB  - Hypoxia in neonates can lead to biochemical and molecular alterations mediated
      through changes in neurotransmitters resulting in permanent damage to brain. In
      this study, we evaluated the changes in the receptor status of GABA(A) in the
      cerebral cortex and brainstem of hypoxic neonatal rats and hypoxic rats
      supplemented with glucose and oxygen using binding assays and gene expression of
      GABA(Aalpha1) and GABA(Agamma5). In the cerebral cortex and brainstem of hypoxic
      neonatal rats, a significant decrease in GABA(A) receptors was observed, which
      accounts for the respiratory inhibition. Hypoxic rats supplemented with glucose
      alone and with glucose and oxygen showed a reversal of the GABA(A) receptors,
      andGABA(Aalpha1) and GABA(Agamma5) gene expression to control. Glucose acts as an
      immediate energy source thereby reducing the ATP-depletion-induced increase in
      GABA and oxygenation, which helps in encountering anoxia. Resuscitation with
      oxygen alone was less effective in reversing the receptor alterations. Thus, the
      results of this study suggest that reduction in the GABA(A) receptors functional
      regulation during hypoxia plays an important role in mediating the brain damage.
      Glucose alone and glucose and oxygen supplementation to hypoxic neonatal rats
      helps in protecting the brain from severe hypoxic damage.

PMID- 20033842
TI  - Traction removal of percutaneous endoscopic gastrostomy devices in children.
AB  - BACKGROUND: There are few published data on non-endoscopic removal of
      percutaneous endoscopic gastrostomy devices in children. AIMS: To describe
      prospective data acquired for traction removal of percutaneous endoscopic
      gastrostomy devices at a single pediatric center over a 5-year period. METHODS:
      Data were obtained from endoscopy records, computerized hospital patient
      information systems and case note analysis. The device that could be removed by
      traction was the Corflo (Merck) 12-Fr percutaneous endoscopic gastrostomy tube
      with a collapsible internal retention dome. All procedures were performed under
      general anesthesia. RESULTS: Between 2002-2006, 220 children underwent
      percutaneous endoscopic gastrostomy removals (166 by traction, 51 endoscopically
      and 3 Foley catheter to button conversions). The median duration between
      percutaneous endoscopic gastrostomy insertion and low profile button device
      substitution was 0.83 years (0.12-3.86). Complications from traction removal
      included internal retention dome separation in two cases (allowed to pass per
      rectum, uneventfully), failure to a insert a low profile button device needing
      percutaneous endoscopic gastrostomy reinsertion, enterocutaneous fistula
      requiring surgical closure in one patient and laparoscopy for suspected low
      profile button device misplacement in one instance. The material cost of
      endoscope disinfection (L10) and disposable usage (L80) avoided by traction
      removal was calculated at L90 per procedure. CONCLUSION: No mortality occurred as
      a result of the traction removal of percutaneous endoscopic gastrostomy tubes.
      Laparoscopy for suspected low profile button device misplacement was needed in
      one case (0.60%). Traction removal of percutaneous endoscopic gastrostomy tubes
      was generally safe and a cost-saving procedure in our experience.

PMID- 20033841
TI  - Reconstitution of secreted frizzled-related protein 1 suppresses tumor growth and
      lung metastasis in an orthotopic model of hepatocellular carcinoma.
AB  - BACKGROUND: Secreted Frizzled-related protein 1 (sFRP1) is frequently silenced in
      many types of cancer, including hepatocellular carcinoma (HCC), leading to
      aberrant activation of Wnt signaling and thereby facilitating tumor development.
      In this study, we aimed to investigate whether restoration of sFRP1 affected HCC
      growth and metastasis. METHODS: We generated stable cell lines overexpressing
      sFRP1 in MHCC97-H cells, which naturally do not express detectable sFRP1
      messenger RNA (mRNA) and have high metastatic properties. The effects of sFRP1
      reexpression on tumor growth and metastasis were assessed in vitro and in vivo.
      It was also tested whether beta-catenin signaling mediated the function of sFRP1
      in tumor progression. RESULTS: Overexpression of sFRP1 substantially diminished
      the proliferation and invasion potentials of MHCC97-H cells. Furthermore, sFRP1
      expression significantly inhibited MHCC97-H xenograft growth and metastasis in
      vivo, which was accompanied by decreased angiogenesis and increased tumor cell
      apoptosis. Moreover, sFRP1 overexpression caused less expression of beta-catenin
      and its downstream effector genes cyclin D1 and matrix metalloproteinase (MMP)-2.
      CONCLUSION: Together these findings demonstrate that sFRP1 reconstitution
      suppresses tumor growth, angiogenesis, and metastasis in MHCC97-H xenografts,
      which may be associated with inactivation of beta-catenin signaling, thus
      providing a possible therapeutic strategy against HCC.

PMID- 20033843
TI  - Survivin expression in colorectal carcinomas: correlations with
      clinicopathological parameters and survival.
AB  - BACKGROUND: Survivin is a new member of the Inhibitor of apoptosis protein family
      that has a dual function as a mitotic regulator and apoptosis inhibitor. Survivin
      is prominently expressed in transformed cell lines and in many human cancers,
      including colorectal carcinoma. The aim of this study is to investigate the
      expression of survivin in colorectal carcinomas and its possible associations
      with clinicopathological parameters and patient survival. MATERIALS AND METHODS:
      Sections of formalin-fixed paraffin-embedded tissues from 77 colorectal
      carcinomas were immunohistochemistry stained for survivin. RESULTS: Survivin was
      mainly detected in the bottom of the glands of normal mucosa with mainly
      cytoplasmic localization. No survivin expression was found in infiltrating
      lymphocytes, fibroblasts, smooth muscle cells or neural tissue. Survivin staining
      was detected in 68/77 (88.3%) colorectal carcinomas. Survivin expression was
      found to be significantly associated with tumor differentiation (P = 0.02) but
      not with gender, age or Dukes stage. Survival did not differ according to
      survivin expression. CONCLUSION: Survivin was found in the majority of colorectal
      carcinomas, suggesting that its expression is an early event in colorectal
      carcinogenesis. Its expression is statistically significantly associated with
      tumor differentiation but not with patient survival.

PMID- 20033844
TI  - Association of intussusception and celiac disease in adults.
AB  - INTRODUCTION: Intussusception (IS) is rare in adults. However, the more frequent
      use of cross-sectional imaging has resulted in an increase in its detection.
      Because of the reported association with celiac disease, we determined the
      prevalence of IS among a cohort with celiac disease. METHODS: An anonymized
      prospectively maintained celiac disease database and radiological database were
      reviewed. RESULTS: Of a total of 880 patients, 14 (age 47 +/- 17.5 years; 50%
      female) had IS that was detected by CT in 10, capsule endoscopy in three, and
      barium studies in two. The reason for evaluation was abdominal pain in 78%
      (11/14), whereas in the remainder (3/14) were incidental. IS was the initial
      manifestation of celiac disease in 57% (8/14). Two patients were found to have
      lead-point intussusceptions and both had small-bowel adenocarcinoma, and 10/14
      had severe villous atrophy (subtotal or total). Among those with established
      celiac disease, IS was detected early, within 3 years of diagnosis. Follow-up was
      available for 11 patients, 9 of who adhered strictly to a gluten-free diet, and
      six had no recurrence. Among all the patients diagnosed with IS on radiologic
      studies at our institution, 45 were considered to have idiopathic IS. Only two of
      these patients had evaluation for celiac disease. CONCLUSION: IS occurs in celiac
      disease. It may be the initial presentation and is associated with abdominal
      pain. Adenocarcinoma needs to be excluded. The majority of patients do not have
      recurrent symptoms after adherence to a gluten-free diet. Celiac disease should
      be considered more frequently when IS is encountered.

PMID- 20033845
TI  - Association between posttraumatic stress disorder following myocardial infarction
      and liver enzyme levels: a prospective study.
AB  - BACKGROUND: Research in rodents demonstrated that psychological stress increases
      circulating levels of alanine transaminase, aspartate transaminase, and alkaline
      phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress
      disorder and transaminases predicted coronary heart disease. AIMS: To investigate
      the hypothesis that severity of posttraumatic stress disorder following
      myocardial infarction would prospectively relate to liver enzymes. METHODS: Study
      participants were 24 patients (mean 59+/-7 years, 79% men) with an interviewer
      rated diagnosis of posttraumatic stress disorder caused by an index myocardial
      infarction 3+/-3 months before. After a mean follow-up of 26+/-6 months, patients
      had a clinical interview to reassess posttraumatic stress disorder severity, a
      medical history, and blood collected to determine liver enzymes. RESULTS: Total
      posttraumatic stress disorder symptoms assessed at study entry prospectively
      predicted plasma levels of alanine transaminase (r=.47, p=.031) and alkaline
      phosphatase (r=.57, p=.004), but not of aspartate transaminase (p=.15),
      controlling for follow-up duration and antidepressant use. Total posttraumatic
      stress disorder symptoms assessed at follow-up were associated with alanine
      transaminase (r=.72, p=.004), aspartate transaminase (r=.60, p=.018), and
      alkaline phosphatase (r=.64, p=.001) in the 16 patients who had maintained
      diagnostic posttraumatic stress disorder, but not in all 24 patients.
      CONCLUSIONS: The severity of posttraumatic stress disorder following myocardial
      infarction was associated with mild increase in liver enzyme levels, suggesting
      that chronic psychological stress relates to hepatic damage in humans. This might
      help to explain the previously observed increased cardiovascular risk in
      chronically traumatized individuals.

PMID- 20033846
TI  - Phenotypic characteristics and diagnoses of patients referred to an iron overload
      clinic.
AB  - BACKGROUND: There are limited data on the phenotypic differences between patients
      with hereditary hemochromatosis (HH) and other forms of iron overload. AIMS: To
      describe and compare patients suspected of having iron overload disease. METHODS:
      Patients were evaluated at a university iron overload clinic over a 5-year
      period. Biochemical and clinical profiles of patients with HH and non-HH causes
      of suspected iron overload were retrospectively compared. RESULTS: A total of 270
      patients were evaluated during the enrollment period, and 137 (51%) were
      diagnosed with HH. The most common reasons for referral were elevated serum iron
      markers (155 patients), followed by positive family history (40 patients), and
      known HH (75 patients). In patients without HH referred for suspected iron
      overload, the most common diagnoses were nonalcoholic fatty liver disease (NAFLD)
      (24%), chronic hepatitis C infection (14%), and alcohol related liver disease
      (9%). Of the patients with HH, 108 were C282Y homozygotes, 20 were compound
      heterozygotes (C282Y/H63D), and nine had neither mutation. The following clinical
      characteristics were significantly different (p < 0.05) between patients with HH
      and all other referred patients: arthralgia (42 vs. 16%) and decreased libido (11
      vs. 4%). There was a non-significant trend towards increased fatigue (44 vs.
      33%), diabetes (10 vs. 6%), impotence (8 vs. 4%), and hypothyroidism (10 vs. 6%)
      in the HH group. CONCLUSIONS: (1) A large proportion of patients referred for
      suspected iron overload have diagnoses other than HH. (2) NAFLD, chronic
      hepatitis C, and chronic alcohol use were the most common alternative diagnoses.
      (3) Arthralgia and fatigue are the most common symptoms among patients with HH.

PMID- 20033847
TI  - Validation of ICD-9-CM diagnostic codes for inflammatory bowel disease among
      veterans.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is well described among young whites
      and less so among the elderly and non-whites. Population-level data is required
      to assess outcomes among minority groups. AIM: To validate diagnostic codes for
      IBD from the Department of Veterans Affairs. METHODS: National databases were
      used to identify local patients with Crohn's disease (CD) and ulcerative colitis
      (UC), the extra-intestinal manifestations and surgical procedures associated with
      IBD. Diagnosis was confirmed by manual chart abstraction. Multivariable logistic
      regression was used to derive diagnostic algorithms for CD and UC, which were
      then validated in an independent cohort. RESULTS: The test cohort of 3,827
      patients (1,316 potential cases, 2,511 random controls) was predominantly male
      (94%), white (56%), and of age of 58 (standard deviation 15). The positive
      predictive value (PPV) of CD codes was superior (88-100%) to UC (50-93%). The
      accuracy of extra-intestinal manifestations and surgeries was poor (PPV 0-29%).
      ICD-9-CM code 555.x without 560.9 had a PPV of 91% for CD in the validation
      cohort. Code 556.x with age, gender, and race factors was highly predictive of UC
      (c-statistic 0.9, PPV of 81%). CONCLUSION: VA administrative data can diagnose
      elderly and non-white patients with IBD.

PMID- 20033849
TI  - Utilization of prosodic information in syntactic ambiguity resolution.
AB  - Two self paced listening experiments examined the role of prosodic phrasing in
      syntactic ambiguity resolution. In Experiment 1, the stimuli consisted of early
      closure sentences (e.g., "While the parents watched, the child sang a song.")
      containing transitive-biased subordinate verbs paired with plausible direct
      objects or intransitive-biased subordinate verbs paired with implausible direct
      objects. Experiment 2 also contained early closure sentences with transitively
      and intransitive-biased subordinate verbs, but the subordinate verbs were always
      followed by plausible direct objects. In both experiments, there were two
      prosodic conditions. In the subject-biased prosodic condition, an intonational
      phrase boundary marked the clausal boundary following the subordinate verb. In
      the object-biased prosodic condition, the clause boundary was unmarked. The
      results indicate that lexical and prosodic cues interact at the subordinate verb
      and plausibility further affects processing at the ambiguous noun. Results are
      discussed with respect to models of the role of prosody in sentence
      comprehension.

PMID- 20033850
TI  - Estimating design space available for polyepitopes through consideration of major
      histocompatibility complex binding motifs.
AB  - Major histocompatibility complex (MHC ) epitope presentation is needed for robust
      adaptive immune responses. Core peptide binding motifs for class I and class II
      MHC are 8-10 amino acids long, containing two or more "anchor" residues. These
      binding motifs define epitope anchor amino acid content and spacing, and
      knowledge of them has facilitated emergence of polyepitope vaccines. However,
      polyepitopes can exhibit "junctional epitopes" (neoepitopes interfering with
      vaccine function) resulting from juxtaposition of authentic epitopes. We have
      developed an algorithm for consideration of polyepitope sequence in light of MHC
      motifs to exhaustively identify all junctional-free polyepitope designs for any
      given set of authentic epitopes, and in so doing discovered that the number of
      such variants of any given polyepitope can be astronomically high. Our approach
      designs polyepitopes of any length, considers multiple MHC class I or class II
      motifs simultaneously and can be adapted to design variants of existing proteins
      with pre-selected epitope contents. We have also implemented the algorithm as a
      computer-based tool (CANVAC II), which we make available to interested parties.
      The vast diversity of junctional-free polyepitopes suggests that the number of
      potential T-helper epitope free protein variants may also be large, which may
      have implications for discovery of bioactive but non-immunogenic therapeutics.

PMID- 20033848
TI  - Speech perception among school-aged skilled and less skilled readers.
AB  - This study investigated the relationship between speech perception, phonological
      processing and reading skills among school-aged children classified as 'skilled'
      and 'less skilled' readers based on their ability to read words, decode non
      words, and comprehend short passages. Three speech perception tasks involving
      categorization of speech continua differing in voicing, place and manner of
      articulation were administered and compared to phonological processing skills in
      phonological awareness, speeded naming and verbal short-term memory. The results
      obtained suggested that (a) speech categorization among skilled readers differed
      from that of less skilled readers, (b) speech perception skills were associated
      with both reading and phonological processing skills among both skilled and less
      skilled readers, however, (c) a strong association between speeded naming and
      both word and passage reading skills found among skilled readers was absent among
      less skilled readers. These results suggested that phonological representations
      and/or activation may not be as well developed in less skilled readers.

PMID- 20033851
TI  - Downregulation of Wnt-mediated ROS generation is causally implicated in
      leprechaunism.
AB  - Although mutations in the insulin receptor have been causally implicated with
      leprechaunism, the full pathophysiology of the syndrome cannot be accounted for
      by malfunction of this gene alone. We sought to characterize a connection between
      Wnt-mediated cell signaling and the production of reactive oxygen species (ROS)
      which revealed a novel mechanistic basis for understanding the pathogenesis of
      leprechaunism. To identify candidate genes involved in this process, a PCR-based
      subtractive hybridization was performed. Candidate genes were examined for
      interaction with the Wnt signaling pathway and ROS generation. We found that
      Dickkopf 1 (Dkk1), a Wnt inhibitor, is overexpressed in skin fibroblast cells
      derived from three leprechaunism patients and that the cells showed an impaired
      response to Wnt2 in terms of beta-catenin-Tcf activation. Knockdown of Dkk1 in
      the patient cell lines rescued Wnt2-mediated Tcf activation. Concerted action of
      Wnt2 and knockdown of Dkk1 resulted in enhanced Nox4 expression and PDGF-induced
      ROS generation compared to parental patient cells. Furthermore, we found that
      NFATc2 was activated in response to Wnt2 stimulation and directly activates Nox4
      expression. These data show a crosstalk between Wnt and ROS pathways which in
      turn provides new mechanistic insights at the molecular level into the
      pathogenesis of leprechaunism.

PMID- 20033852
TI  - Expression of p25, an aberrant cyclin-dependent kinase 5 activator, stimulates
      basal secretion in PC12 cells.
AB  - Although alterations in the functions of neurotransmitter systems have been
      implicated in the pathology of Alzheimer's disease (AD), the mechanisms that give
      rise to these alterations are not well understood. The amount of p25, an aberrant
      cleavage product of p35 that activates cyclin-dependent kinase 5 (Cdk5), is
      elevated in AD brains. The role of Cdk5 in neurotransmitter release has been well
      established. In this study, we examined whether p25 was linked to altered
      neurotransmitter release in AD. Transient or stable expression of p25
      significantly increased basal secretion of human growth hormone (hGH) or
      neurotransmitter in PC12 cells. Expression of a p25 phosphorylation-deficient
      mutant, T138A, inhibited basal hGH secretion relative to the p25 wild type,
      suggesting the involvement of Thr138 phosphorylation in secretion. The expression
      and activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), a
      key protease in the generation of beta-amyloid, are increased in AD brains. Our
      previous studies indicated that overexpression of BACE1 enhanced basal secretion
      of hGH in PC12 cells. Transient coexpression of p25 and BACE1 further stimulated
      spontaneous basal secretion. These results indicate a novel role for p25 in the
      secretory pathway and suggest that elevated levels of p25 and BACE1 in AD brains
      may contribute to altered neurotransmitter pathology of AD through enhancing
      spontaneous basal secretion.

PMID- 20033853
TI  - Podophyllotoxin induces CREB phosphorylation and CRE-driven gene expression via
      PKA but not MAPKs.
AB  - CRE-driven luciferase reporter is commonly used in drug screening systems
      involving G protein-coupled receptors (GPCRs). In a screen campaign designed to
      search for melanocortin-4 receptor (MC4R) agonists, podophyllotoxin, a
      microtubules disruptor, was found to induce cAMP-responsive element (CRE)-driven
      reporter expression. MC4R was not involved because podophyllotoxin induced CREB
      activation and CRE-driven transcription in cells not expressing MC4R. Previous
      studies indicated that intracellular calcium, PKA, and MAPKs are involved in CREB
      phosphorylation and activation. Our studies revealed that podophyllotoxin did not
      affect intracellular calcium level and the phosphorylation state of p38.
      Podophyllotoxin induced JNK and ERK activation, but blockade of JNK and ERK
      activation with specific inhibitors had no effect on podophyllotoxin-induced CREB
      activation and CRE-regulated gene expression. Further experiments revealed that
      H89, a specific inhibitor of PKA, significantly inhibited podophyllotoxin-induced
      CREB activation. Podophyllotoxin itself did not alter intracellular cAMP level.
      Taken together, podophyllotoxin induces CREB activation and CRE-driven gene
      expression via PKA activation by a cAMP-independent mechanism.

PMID- 20033854
TI  - Alpha-mannosidases from the digestive fluid of Rhynchophorus Palmarum larvae as
      novel biocatalysts for transmannosylation reactions.
AB  - Two biological fluids, namely hemolymph and digestive fluid from the larval stage
      of Rhynchophorus palmarum Linneaus, a serious pest in agroecosystem exploiting
      oil palm, were screened for hydrolytic activities, by the use of synthetic and
      natural glycoside substrates. Several exo and endoglycosidase activities were
      observed but, the interesting alpha-mannosidase activity (0.41 +/- 0.04 UI) had
      attracted our attention. So, we have previously demonstrated that this activity
      harbours four distinctive alpha-mannosidase isoforms named RpltM, RplM1, RplM2
      and RplM3. We have extended this work to determine the ability of these enzymes
      to catalyze synthesis reactions. Finally, we have revealed that, alpha
      mannosidases from the digestive fluid of R. palmarum larvae catalyze
      transmannosylation reactions. The stability of the enzymes and the optimization
      of the transfer product yield were studied as functions of pH, enzyme unit,
      starting concentration of donor or acceptor and time. It was shown that, in
      experimental optimum conditions, average yields of 12.34 +/- 0.75, 12.15 +/-
      0.79, 5.59 +/- 0.35 and 8.43 +/- 0.50% were obtained for the alpha-mannosidases
      RpltM, RplM1, RplM2 and RplM3, respectively. On the basis of this work, alpha
      mannosidases from the digestive fluid of Rhynchophorus palmarum larvae appear to
      be a valuable tool for the preparation of neoglycoconjugates.

PMID- 20033855
TI  - Therapy refractory coronary compression caused by a cardiac metastasis: The role
      of imaging.

PMID- 20033856
TI  - Myocardial perfusion SPECT identifies patients with left bundle branch block
      patterns at high risk for future coronary events.
AB  - BACKGROUND: The value of myocardial perfusion SPECT (MPS) for patients with left
      bundle branch block (LBBB) or right ventricular apical (RVA) pacing seems
      reduced. The prognosis of patients with only abnormal activation related
      perfusion defects (AARD) due to LBBB or RVA-pacing is similar to those with a
      normal MPS. We assessed the prognostic value of MPS in patients with LBBB or RVA
      pacing. METHODS: Patients with LBBB or RVA pacing referred for vasodilator stress
      MPS between April 2002 and January 2006 were analyzed. Group 1 are patients with
      normal MPS and MPS with AARD. Group 2 are patients with an MPS with a perfusion
      defect extending outside the AARD area. Events were cardiac death, acute
      myocardial infarction and coronary revascularization. RESULTS: In Group 1 (101
      patients) 12 events and in Group 2 (96 patients) 45 events occurred during a mean
      follow-up of 2.6 +/- 1.5 years. The prognosis of Group 2 was significantly worse
      (49%) compared with Group 1 (91%). The annual cardiac death rate was 0.7%/year in
      Group 1 and 6.4%/year in Group 2 (P < .001). The prognosis of patients with LBBB
      was not different from those with RVA pacing. CONCLUSION: Group 2 had a
      significantly worse cardiac prognosis compared to Group 1. The annual cardiac
      death rate of <1% in Group 1 warrants a watchful waiting strategy, whereas the
      cardiac death rate in Group 2 warrants aggressive invasive coronary strategies.

PMID- 20033857
TI  - Prognostic role of myocardial single photon emission computed tomography in the
      elderly.
AB  - The increase in average life expectancy will move the burden of coronary artery
      disease (CAD) to older patients. Myocardial perfusion imaging by single photon
      emission computed tomography (SPECT) has been extensively validated for diagnosis
      and prognostic evaluation in large population series. Yet, its use is usually
      limited in elderly patients in whom, despite increased absolute cardiovascular
      risk, diagnostic and therapeutic work-up is often underperformed. American
      College of Cardiology/American Heart Association guidelines recommend exercise
      ECG testing as the initial noninvasive method for assessment of CAD in patients
      with a normal or near-normal resting ECG, regardless of age. However, a
      considerable proportion of elderly patients is unable to reach an adequate
      workload during the exercise test and the majority of those undergoing for
      standard exercise treadmill score are classified as intermediate risk. In elderly
      patients, SPECT imaging may provide valuable diagnostic and prognostic
      information for clinical management. In particular, normal or near normal SPECT
      identifies elderly patients at low risk of major adverse cardiac events at the
      short-term follow-up.

PMID- 20033858
TI  - Factor Xa-like and fibrin(ogen)olytic activities of a serine protease from
      Hippasa agelenoides spider venom gland extract.
AB  - In the recent past, a low molecular mass serine protease, the Hag-protease that
      caused pro-coagulant activity and as well as local toxicity was isolated and
      characterized from the Hippasa agelenoides spider venom gland extract (Devaraja
      et al., Toxicon 52:130-138, 2008). In the current study, the pro-coagulant
      property has been investigated further and the results are presented. The Hag
      protease reduced the re-calcification time of citrated human plasma. It reduced
      the activated partial thromboplastin time (APTT), and prothrombin time (PT)
      suggesting its participation in common pathway of blood coagulation.
      Interestingly, it coagulated the citrated human plasma in the absence of CaCl(2)
      but, it was lacking thrombin-like activity as it did not clot the purified
      fibrinogen. Strikingly, the enzyme coagulated the factor X deficient congenital
      human plasma, suggesting the factor Xa-like activity. However, the cumulative
      augmented activity was observed in presence of CaCl(2) and phospholipids.
      Further, the Hag-protease preferentially hydrolyzed the Aalpha chain and then the
      Bbeta-chain, but not the gamma-chain. As a result, truncated fibrinogen generated
      was lacking in the polymerization property. It hydrolyzed all the subunits of
      partially cross-liked fibrin clot (alpha-polymer, alpha-chain, beta-chain, and
      gamma-gamma dimers). Further, at low concentrations, the Hag-protease stimulated
      the aggregation of human platelets in platelet rich plasma, but at high
      concentrations caused spontaneous clumping. In contrast, it inhibited the
      collagen induced aggregation of washed human platelets. In summary, the present
      study for the first time reporting the factor Xa-like activity of a serine
      protease especially from the spider venom that exhibited opposing effects on
      hemostasis, the pro-coagulant activity and the anti-coagulant activity including
      fibrin(ogen)olytic and platelet aggregation inhibition activities.

PMID- 20033859
TI  - Heart failure with normal ejection fraction (HFNEF): is it worth considering?
AB  - A significant proportion of patients with heart failure happen to have a normal
      ventricular ejection fraction at echocardiography during examination. Previously
      called diastolic heart failure, it is nowadays referred to as heart failure with
      normal ejection fraction (HFNEF) or HF with preserved ejection fraction. The
      European Society of Cardiology, recognizing the importance of this type of heart
      failure, recently issued new definition criteria for it. This review will discuss
      the different steps that lead to such a diagnosis, as well as some new aspects of
      its pathophysiology. Finally, the management of this form of HF, that is not as
      straightforward as HF due to systolic dysfunction, will be discussed.

PMID- 20033860
TI  - A report of ten patients with thyroid hemiagenesis: ultrasound screening in
      patients with thyroid disease.
AB  - BACKGROUND: Thyroid hemiagenesis (TH) is a rare congenital abnormality of the
      thyroid gland, characterised by the absence of one lobe. The true prevalence of
      this congenital abnormality is not known because the absence of one thyroid lobe
      usually does not cause clinical symptoms by itself. This study aims to identify
      the frequency of TH and associated diseases in outpatients referred to our clinic
      for the first time. SUBJECTS AND METHODS: 6242 outpatients, who were referred to
      our thyroid clinic between January 2008 and March 2009 and underwent thyroid
      ultrasonography, were retrospectively analysed. For patients with TH, demographic
      data, family history of thyroid disorders, drugs administered, thyroid function
      parameters, thyroid autoantibodies were examined and thyroid sonography was
      carried out. Tc99m pertechnetate scintigraphy was performed to confirm the
      diagnosis of hemiagenesis and to rule out coexisting ectopic thyroid tissue.
      RESULTS: We identified 10 cases of TH in 6242 outpatients with various thyroid
      disorders, 8 women and 2 men (ratio 4:1), age 21-63 years, indicating a
      prevalence of 0.16%. Associated thyroid disease in these patients included: 1
      patient with nodular Graves' disease, 1 with Hashimoto's thyroiditis, 4 with
      euthyroid nodular goiters and 2 with euthyroid multinodular goiters. Nine
      patients were clinically asymptomatic. However, the patient with nodular Graves'
      disease presented thyrotoxicosis. CONCLUSIONS: TH is a rare congenital anomaly
      and prevalence of TH in thyroid patients is 0.16%. In our study, the most
      frequently seen thyroid disease accompanying thyroid hemiagenesis was nodular
      goiter.

PMID- 20033863
TI  - Review on experimental research of herbal medicines with anti-amnesic activity.
AB  - Amnesia is characterized by the inability to form memories or total or partial
      loss of memory secondary to cerebral malfunction following degenerative diseases,
      cerebral infections, traumatic injuries and emotional events which could be
      differentiated from dementia. However, no effective treatment for amnesia is
      currently available. Much research effort has been focused on developing new
      drugs from herbal medicines which have multifunctional properties. Novel plant
      extracts and their major or bioactive components including alkaloids, flavonoids,
      glycosides and saponins with promising antioxidant effects, various effects on
      cholinergic, GABAergic, glutaminergic, serotonergic, catecholaminergic and
      histaminergic systems, enhancement of cerebral blood flow and elevation of
      ribonucleic acid (RNA) as well as protein levels have been studied. In this
      review, we discuss the research findings on novel plant extracts and their
      bioactives with anti-amnesic effects on different neurotransmitter systems.
      Developing new drugs from herbal medicines for the treatment of amnesia is a
      hopeful attempt to meet the unmet medical needs.

PMID- 20033864
TI  - The mechanisms for enhanced oral absorption of hydroxysafflor yellow A by
      chuanxiong volatile oil.
AB  - The aims of this study were to investigate the effect of ligusticum chuanxiong
      volatile oil (CVO) on the oral absorption of hydroxysafflor yellow A (HSYA). The
      effects were studied both IN VITRO and IN VIVO. The contents of CVO were measured
      by GC-MS. The Caco-2 cell model was used to evaluate HSYA permeation with or
      without the presence of CVO. Transepithelial electrical resistance (TEER) of the
      Caco-2 cell monolayers was monitored and the alteration in the subcellular
      localization of claudin-1, the tight junction protein, was observed by
      immunofluorescence. The irritation of CVO on rat intestine was studied by
      paraffin slice technology. Our results demonstrated that CVO mainly contained
      ligustilide (47.82 %). The Papp of HSYA was improved by 5.34-fold and 4.62-fold
      in the presence of 0.02 mg/mL and 0.01 mg/mL of CVO, respectively. After opening
      of the tight junctions of the Caco-2 cell monolayer, TEER decreased, the position
      of claudin-1 changed, and its expression increased. CVO at different
      concentrations (10, 25, 100 and 200 mg/kg) caused no significant irritation on
      rat intestine. The bioavailability of HSYA in rats was increased by 6.48-fold and
      4.91-fold when 100 and 25 mg/kg of CVO were co-administrated, respectively. CVO
      was an effective absorption enhancer for oral delivery of BCS III drugs. It can
      cause redistribution of claudin-1 proteins and open the tight junctions.

PMID- 20033865
TI  - Enzyme-linked immunosorbent assay for total isoflavonoids in Pueraria candollei
      using anti-puerarin and anti-daidzin polyclonal antibodies.
AB  - Pueraria candollei (White Kwao Khuer) is a medicinal plant containing puerarin,
      daidzin, genistin, daidzein, and genistein as major isoflavonoids used for its
      rejuvenating and estrogenic effects. In order to analyze these compounds, a
      single enzyme-linked immunosorbent assay (ELISA) for total isoflavonoids was
      developed using anti-puerarin and anti-daidzin polyclonal antibodies (PAbs). The
      range for calibration of isoflavonoids by ELISA was 0.05-6.25 microg/mL. Total
      isoflavonoid concentrations in P. candollei samples determined by the newly
      developed assay system showed good agreement with those analyzed by HPLC. Based
      on validation analysis, this analytical method by ELISA is a precise, accurate,
      and sensitive method for the determination of total isoflavonoids in P.
      candollei.

PMID- 20033866
TI  - Prevention of peritoneal carcinomatosis in mice by combining hyperthermal
      intraperitoneal chemotherapy with the water extract from Burr parsley (Caucalis
      platycarpos L.).
AB  - The presence of peritoneal carcinomatosis arising from gastrointestinal and
      gynecologic tumors is associated with a poor prognosis. Animal models of
      peritoneal carcinomatosis are important in the evaluation of new treatment
      modalities. The purpose of this study was to investigate the effect of local
      chemoimmunotherapy and hyperthermal intraperitoneal chemotherapy (HIPEC) in an
      animal model of induced peritoneal carcinomatosis in the mouse. For induction of
      peritoneal carcinomatosis, cells from transplantable mammary carcinoma (MCa) were
      implanted intraperitoneally in CBA mice. Seven or 3 days before implantation of
      MCa cells (5 x 10 (3)) the mice were injected with lyophilized water extract from
      CAUCALIS PLATYCARPOS L. (CPL; 200 mg . kg (-1)) into the abdominal cavity.
      Immediately after implantation of MCa cells in the abdominal cavity, mice were
      treated two times with 2 mL of saline that was heated either at 37 degrees C or
      43 degrees C (hyperthermal treatment) and cytostatics (doxorubicin 20 mg . kg (
      1), cisplatin 10 mg . kg (-1), mitomycin 5 mg . kg (-1), 5-FU 150 mg . kg (-1)).
      We followed the survival of animals and the side effects appearing with different
      forms of treatment. CPL increased the life span of mice with peritoneal
      carcinomatosis without hyperthermal treatment (ILS% = 32.55 %) but showed no
      effect on the life span of mice with hyperthermal treatment (ILS% = 1.44).
      Combined treatment with CPL and cytostatics (CIS, DOX, and MIT) significantly
      affected the development of peritoneal carcinomatosis and increased the survival
      of mice (ILS% - 37 degrees C = 144.17, 415.46, and 124.13, ILS% - 43 degrees C =
      311.42, 200.74, and 138.33, respectively). However, intraperitoneal chemotherapy
      with 5-FU alone resulted in greater survival time of mice than the treatment with
      5-FU + CPL. Results suggest the synergistic effect of hyperthermia, chemotherapy,
      and immunotherapy. CPL significantly increases the antitumor activity of the
      hyperthermic chemotherapy and the survival rate of mice with peritoneal
      carcinomatosis. The stimulative effect of CPL on immunomodulation may be a
      possible mechanism which protects mice from developing peritoneal carcinomatosis
      and reduces the side effects of chemotherapy, increasing the life span of mice.

PMID- 20033867
TI  - Comparison of the enteric mucosal immunomodulatory activity of combinations of
      Coptis chinensis Franch. Rhizomes and Evodia rutaecarpa (Juss.) Benth. Fruits in
      mice with dextran sulphate sodium-induced ulcerative colitis.
AB  - Combinations of crude rhizomes of Coptis chinensis Franch., Ranunculaceae, and
      fruits of Evodia rutaecarpa (Juss.) Benth., Rutaceae, at a ratio of 6 : 1
      (formula A) and 1 : 6 (formula B) were extracted with boiling water, and their
      modulatory activity on enteric mucosal immune responses in mice with dextran
      sulphate sodium-induced ulcerative colitis was investigated. The results showed
      that both formulas could reduce the severity of inflammation in the colon.
      Formula A at a low dose can decrease myeloperoxidase (MPO) activity, and formula
      B was inactive. Both formulas did not affect the percentages of CD4 (+) and CD8
      (+) T cells in the periphery, but they evoked an increase of CD8 (+) T cells
      among the enteric intraepithelial lymphocytes. Formula B at a low dose could
      increase both CD4 (+) and CD8 (+) cells, and formula A at a high dose could only
      increase CD8 (+) T cells among the Peyer's patch lymphocytes (p < 0.05). Both
      formulas did not affect the percentages of CD4 (+) and CD8 (+) T cells among the
      lamina propria lymphocytes, but decreased the serum concentration of IL-1 beta (p
      < 0.05 at a low dose of formula A) and enhanced the level of IL-10 in serum (p <
      0.05 at a low dose formula B). We conclude that both formulas have a similar
      modulating effect on enteric mucosal immune responses, the major difference being
      that formula A could decrease the level of IL-1 beta, while formula B could
      increase the IL-10 dose in serum.

PMID- 20033868
TI  - The licorice flavonoid isoliquiritigenin suppresses phorbol ester-induced
      cyclooxygenase-2 expression in the non-tumorigenic MCF-10A breast cell line.
AB  - Cyclooxygenase (COX) is the rate-limiting enzyme for the conversion of
      prostaglandins from arachidonic acid. Upregulation of COX-2 has been well
      documented during tumorigenesis and metastasis of breast cancer.
      Isoliquiritigenin (ILN), a flavonoid isolated from licorice (the rhizomes of
      GLYCYRRHIZA GLABRA, a member of the bean plant family), is known to be a
      potential suppressor of COX-2 expression. This study focuses on phorbol ester
      induced COX-2 expression in the non-tumorigenic MCF-10A cells. Real-time PCR and
      Western blotting indicated that ILN at 5 microM or above significantly inhibited
      phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in the breast
      cells. The activated PKC alpha appeared to be not affected, whereas its
      downstream mitogen-activated protein kinase (MAPK) ERK-1/2 was deactivated. ERK
      can activate the transcriptional factor binding of AP-1 or CRE, which can be
      located at the COX-2 promoter region (- 72/- 53). Electrophoretic mobility shift
      assays illustrated that ILN suppressed DNA binding at this region. The shifted
      bands could be competed off with consensus sequences of AP-1 and CRE, and the
      supershift assay demonstrated that CREB-1 instead of c-Jun was responsible for
      the binding. This study showed that ILN downregulated PMA-induced COX-2
      expression by modulating ERK-1/2 signaling, a finding that may be relevant to the
      disease prevention properties of licorice.

PMID- 20033870
TI  - [In Process Citation].

PMID- 20033869
TI  - Characterisation of chamomile volatiles by simultaneous distillation solid-phase
      extraction in comparison to hydrodistillation and simultaneous distillation
      extraction.
AB  - A new method for complete separation of steam-volatile organic compounds is
      described using the example of chamomile flowers. This method is based on the
      direct combination of hydrodistillation and solid-phase extraction in a
      circulation apparatus. In contrast to hydrodistillation and simultaneous
      distillation extraction (SDE), an RP-18 solid phase as adsorptive material is
      used rather than a water-insoluble solvent. Therefore, a prompt and complete
      fixation of all volatiles takes place, and the circulation of water-soluble
      bisabololoxides as well as water-soluble and thermolabile en-yne-spiroethers is
      inhibited. This so-called simultaneous distillation solid-phase extraction (SD
      SPE) provides extracts that better characterise the real composition of the
      vapour phase, as well as the composition of inhalation vapours, than do SDE
      extracts or essential oils obtained by hydrodistillation. The data indicate that
      during inhalation therapy with chamomile, the bisabololoxides and spiroethers are
      more strongly involved in the inhaling activity than so far assumed.

PMID- 20033871
TI  - [Switzerland as a "Veterinary Area": The development of federal veterinary
      policy, A.D. 941 - 1886.].
AB  - The earliest recorded animal disease notification on the territory of
      contemporary Switzerland is found in the chronicles of the monastery of St. Gall
      and dates back to A.D. 941. Disease control in Switzerland began in medieval
      towns, with the regulation of livestock and the meat trade. Later, there were
      attempts to keep entire small areas such as valleys free of animal epidemics.
      Because livestock tended to be transported in one direction only - away from
      rural areas for sale in towns and for export - disease in animal-raising areas
      usually did not spread very far. Albrecht von Haller's epidemiological research
      from 1773 established the fundamentals of effective disease control. The cantons
      introduced extensive measures for protecting their territories on the basis of
      animal transport controls. With the development of the railways and the
      international livestock trade around 1850, the risk of animal epidemics increased
      considerably, leading to the need for measures on national and international
      levels. The first federal law on animal disease control was introduced in
      Switzerland in 1872, thus creating a nation-wide "veterinary area". In 1886 the
      law was amended to include mandatory controls of imported livestock and meat by a
      newly-created border veterinary service.

PMID- 20033872
TI  - [Meat inspection in the medieval Zahringer towns.].
AB  - An explanation of medieval practices of meat supply and regulation, using
      examples drawn from the so-called "Zahringer towns" founded by the Dukes of
      Zahringen: Bern, Burgdorf, Thun, Murten, Freiburg and Rheinfelden. For the town
      councils it was important to be able to provide the population with sufficient
      quantities of good-quality meat at fair prices. After the 14th century the
      slaughtering of animals had to be carried out in public slaughterhouses. Meat
      could only be sold publicly, at designated butchers' stalls. Meat and organs were
      checked on a daily basis by the town's meat inspectors, who verified the names
      under which products were sold, their price, and hygienic conditions, including
      the absence of tapeworm larvae. In addition to the publicly-regulated meat trade,
      town dwellers could also buy meat products at the markets, and could raise their
      own pigs, sheep and goats to be slaughtered in the back alleys. Permission to
      raise small livestock at home was a privilege granted by the town council. The
      sale of meat by non-resident peddlers was officially forbidden, but could not be
      prevented entirely.

PMID- 20033873
TI  - [The history of horseshoing.].
AB  - The mankind has used the domesticated horse since the beginning constantly. The
      consequence was often lameness because of intensive wear of hoofsole. With
      different hoof-protective measures and devices mankind tried to deal this
      weakness. Finally the invention of the shoeing solved this problem. We probably
      owe this invention to a Scythian blacksmith from the 4th or 5th A.D. At the
      beginning horseshoeing was only sparingly used. Later improvements and
      innovations brought the breakthrough. Today every horse wears horseshoes.

PMID- 20033874
TI  - [About the cultural history of dog-keeping in the early modern age: A (re)reading
      of rabies treatises.].
AB  - Rabies treatises of the 18th and 19th century are being researched in regard to
      their significance of the keeping of pets, which started to establish itself at
      the beginning of the 17th century. In doing so it is clearly recognizable that
      this keeping of pets had become a constant element of the civil urban life. The
      treatises also show that the physicians declined the keeping of dogs out of pure
      pleasure.

PMID- 20033875
TI  - [My great-grandfather Christian Batschelet (1813 - 1897) veterinarian in
      Walperswil (BE).].
AB  - In the introduction I will start from a biographical novel on Friedrich Baumann,
      who was born in 1835 as an illegitimate child and later stood in high respect as
      building contractor, founder's president of the Swiss master builder's federation
      and politician, and we will look after his father who emigrated to America. In
      the following sections I will present the Batschelet family as well as the family
      of the veterinarian Christian Batschelet and the department for animal
      pharmaceutics of the academy in Bern. The time of the young veterinarian in
      Walperswil as well as his emigration and his life in the USA will also be
      examined and I will also introduce Christian Batschelet's son, Friedrich Baumann
      and his son, my father Erwin Friedrich Baumann.

PMID- 20033877
TI  - [In Process Citation].

PMID- 20033876
TI  - [In Process Citation].

PMID- 20033878
TI  - [In Process Citation].

PMID- 20033879
TI  - [Application deadline 1 February 2010.].

PMID- 20033880
TI  - Does the addition of non-invasive ventilation during pulmonary rehabilitation in
      patients with chronic obstructive pulmonary disease augment patient outcome in
      exercise tolerance? A literature review.
AB  - BACKGROUND: Non-invasive ventilation (NIV) during exercise in patients with
      chronic obstructive pulmonary disease (COPD) has been shown to increase exercise
      time and intensity. Feasibly then, NIV during pulmonary rehabilitation will
      enhance post-rehabilitation training effects. The purpose of this review is to
      systematically consider and critique the literature concerning the effects of
      NIV, when used during an exercise programme in COPD patients on exercise
      tolerance. METHOD: An electronic literature search was completed and the
      reference lists of the articles that fitted the following inclusion criteria were
      screened. Studies that used any mode of NIV during an exercise programme with a
      primary outcome measure focusing on exercise tolerance and were written after the
      year 2000 to reflect current practice. Studies that were not written in English
      or had been included in previous literature reviews were excluded. The studies
      were then critically appraised and assigned a level of evidence based upon
      Scottish Intercollegiate Guidelines Network. RESULTS: Twenty-eight articles were
      screened, of which six fitted the inclusion criteria. The methodological quality
      ranged from level 1- to 1+. All but one study by Bianchi et al. (2002)
      demonstrated a statistically significant improvement in exercise tolerance with
      the addition of some form of NIV during pulmonary rehabilitation. The benefits
      may be greater in patients with more severe airway obstruction as determined by
      Forced Expiration Volume (FEV), (%pred). CONCLUSION: This review would suggest
      that NIV may allow an increased exercise intensity and duration during pulmonary
      rehabilitation in patients with moderate to very severe COPD, (according to the
      American Thoracic Society guidelines), resulting in a greater training effect and
      a prolonged exercise capacity. Further research looking at long-term follow-up is
      recommended.

PMID- 20033881
TI  - Development and validation of a high-performance liquid chromatography method for
      the simultaneous determination of aspirin and folic acid from nano-particulate
      systems.
AB  - Attention has shifted from the treatment of colorectal cancer (CRC) to
      chemoprevention using aspirin and folic acid as agents capable of preventing the
      onset of colon cancer. However, no sensitive analytical method exists to
      simultaneously quantify the two drugs when released from polymer-based
      nanoparticles. Thus, a rapid, highly sensitive method of high-performance liquid
      chromatography analysis to simultaneously detect low quantities of aspirin
      (hydrolyzed to salicylic acid, the active moiety) and folic acid released from
      biodegradable polylactide-co-glycolide (PLGA) copolymer nanoparticles was
      developed. Analysis was done on a reversed-phase C(18) column using a photodiode
      array detector at wavelengths of 233 nm (salicylic acid) and 277 nm (folic acid).
      The mobile phase consisted of acetonitrile-0.1% trifluoroacetic acid mixture
      programmed for a 30 min gradient elution analysis. In the range of 0.1-100
      microg/mL, the assay showed good linearity for salicylic acid (R(2) = 0.9996) and
      folic acid (R(2) = 0.9998). The method demonstrated good reproducibility, intra-
      and inter-day precision and accuracy (99.67, 100.1%) and low values of detection
      (0.03, 0.01 microg/mL) and quantitation (0.1 and 0.05 microg/mL) for salicylic
      acid and folic acid, respectively. The suitability of the method was demonstrated
      by simultaneously determining salicylic acid and folic acid released from PLGA
      nanoparticles.

PMID- 20033883
TI  - Percutaneous absorption and exposure assessment of pesticides.
AB  - Dermal exposure to a diverse range of chemicals may result from various uses. In
      order to assess exposure and estimate potential risks, accurate quantitative data
      on absorption are required. Various factors will influence the final results and
      interpretations of studies designed to assess the ability of compounds to
      penetrate the skin. This overview will discuss skin penetration by pesticides,
      emphasizing key parameters to be considered from the perspective of exposure
      assessment.

PMID- 20033882
TI  - Candida albicans CaPTC6 is a functional homologue for Saccharomyces cerevisiae
      ScPTC6 and encodes a type 2C protein phosphatase.
AB  - Type 2C protein phosphatases (PP2C) are monomeric enzymes and their activities
      require the presence of magnesium or manganese ions. There are seven PP2C genes,
      ScPTC1, ScPTC2, ScPTC3, ScPTC4, ScPTC5, ScPTC6 and ScPTC7, in Saccharomyces
      cerevisiae. PTC6 is highly conserved in pathogenic and nonpathogenic yeasts. In
      the current study we have demonstrated that the Candida albicans CaPTC6 gene
      could complement the functions of ScPTC6 in the rapamycin and caffeine
      sensitivities of S. cerevisiae cells, indicating that they are functional
      homologues. We have also demonstrated that the CaPTC6-encoded protein is a
      typical PP2C enzyme and that CaPtc6p is localized in the mitochondrion of yeast
      form and hyphal cells. However, deletion of CaPTC6 neither affects cell and
      hyphal growth nor renders Candida cells sensitive to rapamycin and caffeine.
      Therefore, possibly with a functional redundancy to other mitochondrial
      phosphatases, CaPtc6p is likely to be involved in the regulation of a
      mitochondrial physiology.

PMID- 20033884
TI  - The structure of mental disorders re-examined: is it developmentally stable and
      robust against additions?
AB  - Previous research suggests that patterns of comorbidity of a limited number of
      anxiety, depressive, substance use and antisocial personality (ASP) disorders
      among adults are best reflected by a hierarchical three-factor structure with two
      correlated factors ('anxious-misery' and 'fear') that are summarized in a second
      order 'internalizing' factor and one 'externalizing' factor. It has not been
      examined whether this structure is developmentally stable and robust against
      additions of more diagnoses. Using data from a prospective-longitudinal community
      study of adolescents and young adults we re-evaluate the three-factor model
      originally proposed by Krueger (Archives of General Psychiatry, 1999; 56, 921
      926). Using confirmatory factor analysis with identical conventions as in
      Krueger's original work we found that the three factor model did not fit robustly
      across age or a wider range of diagnoses. Using explanatory factor analysis we
      examined alternative structures. We found various clinically meaningful patterns
      with good fit that go substantially beyond the original three-factor structure.
      However, again, there is little consistency in findings when different age groups
      or different diagnoses are considered. Our findings suggest that psychopathology
      cannot be reduced to any simple structure.

PMID- 20033885
TI  - Association of CASP8 D302H polymorphism with reduced risk of aggressive prostate
      carcinoma.
AB  - BACKGROUND: Because of the dramatically different clinical course of aggressive
      and indolent prostate carcinoma (PCa), markers that distinguish between these
      phenotypes are of critical importance. Apoptosis is an important protective
      mechanism for unrestrained cellular growth and metastasis. Therefore, dysfunction
      in this pathway is a key step in cancer progression. As such, genetic variants in
      apoptosis genes are potential markers of aggressive PCa. Recent work in breast
      carcinoma has implicated the histidine variant of CASP8 D302H (rs1045485) as a
      protective risk allele. METHODS: We tested the hypothesis that the H variant was
      protective for aggressive PCa in a pooled analysis of 796 aggressive cases and
      2,060 controls. RESULTS: The H allele was associated with a reduced risk of
      aggressive PCa (OR(per allele) = 0.67, 95% CI: 0.54-0.83, P(trend) = 0.0003). The
      results were similar for European-Americans (OR(per allele) = 0.68; 95% CI: 0.54
      0.86) and African-Americans (OR(per allele) = 0.61; 95% CI: 0.34-1.10). We
      further determined from the full series of 1,160 cases and 1,166 controls in the
      Prostate, Lung, Colorectal, Ovarian (PLCO) population that the protective effect
      of the H allele tended to be limited to high-grade and advanced PCa (all cases
      OR(per allele) = 0.94; 95% CI: 0.79-1.11; localized, low-grade disease OR(per
      allele) = 0.98; 95% CI: 0.79-1.23; and aggressive disease OR(per allele) = 0.73;
      95% CI: 0.50-1.07). CONCLUSION: These results suggest that histidine variant of
      CASP8 D302H is a protective allele for aggressive PCa with potential utility for
      identification of patients at differential risk for this clinically significant
      phenotype.

PMID- 20033886
TI  - Gestational and neonatal-onset hypothyroidism alters androgen receptor status in
      rat prostate glands at adulthood.
AB  - BACKGROUND: Infertility associated with congenital and early childhood
      hypothyroidism is an important reproductive health problem in men. Nevertheless,
      the exact mechanism underlying hypothyroidism-induced changes in the prostate
      gland, an androgen-dependent organ that contributes a significant portion of the
      seminal plasma remains obscure. The present study tested the hypothesis
      "transient gestational- or neonatal-onset hypothyroidism may have duration
      dependent and lobe specific effect on androgen receptor (AR) status in the
      prostate glands of adult rats." METHODS: Hypothyroidism was induced in pregnant
      and lactating rats by feeding 0.05% methimazole (MMI) through drinking water
      during fetal and neonatal milestones of testicular and prostatic development.
      Pregnant dams had MMI exposure from 9th day post-coitum (dpc) to 14 dpc (group
      II) or 21 dpc (group III). Lactating mothers had MMI exposure from day 1 post
      partum (dpp) to 14 dpp (group IV) or up to 29 dpp (group V). AR status in the
      dorsolateral and ventral prostate lobes (DLP and VP) of the pups was assessed by
      RT-PCR, western blot and radio receptor assay. RESULTS: AR mRNA expression
      consistently decreased in the DLP of all groups, whereas it increased in VP of
      group III and V rats. AR protein consistently decreased in both DLP and VP of all
      experimental rats. AR nuclear ligand-binding activity diminished in groups II and
      IV, whereas it increased in groups III and V. CONCLUSION: The results obtained
      support the proposed hypothesis and indicate that an optimum thyroid activity
      during pre- and neonatal period determines AR status in the prostate glands at
      adulthood.

PMID- 20033887
TI  - Racial differences in prostate cancer risk remain among US servicemen with equal
      access to care.
AB  - BACKGROUND: Prostate cancer is the most common cancer among US men, however, the
      etiology remains unclear. Yet, one consistency is that black non-Hispanic men are
      at increased risk for prostate cancer compared to white, non-Hispanic men. The
      goal of this study was to assess relations between demographic and other
      potential prostate cancer risk factors in the context of the US military
      healthcare system, which provides equal access to all US servicemen. METHODS:
      Military healthcare and demographic data were used to describe risk factors for
      prostate cancer in the US military from September 1993 to September 2003. Cox's
      proportional hazards regression was employed to model the time to prostate cancer
      hospitalization. RESULTS: Four hundred eight first prostate cancer
      hospitalizations were identified among 2,761,559 servicemen. The adjusted rate
      per 100,000 persons rose from 1.41 to 3.62 for white non-Hispanic men and 1.43 to
      6.08 for black non-Hispanic men by the end of the study. The increasing incidence
      over time for combined race/ethnic groups was similar to trends reported in the
      Surveillance, Epidemiology, and End Results Program for the US civilian
      population. No association was observed between occupation and prostate cancer
      hospitalization. However, black non-Hispanic men were at increased risk compared
      with white non-Hispanic men (hazard ratio = 2.72, 95% confidence interval: 2.12,
      3.49). CONCLUSIONS: No association was observed between occupation and prostate
      cancer hospitalization. In this relatively young cohort, black non-Hispanic
      race/ethnicity was found to be predictive of prostate cancer, and this
      association existed regardless of access to care and socioeconomic status.

PMID- 20033888
TI  - Choice of treatment modalities was not influenced by pain, severity or co
      morbidity in patients with knee osteoarthritis.
AB  - BACKGROUND AND PURPOSE: Patients with knee osteoarthritis (OA) are commonly
      treated by physiotherapists in primary care. The physiotherapists use different
      treatment modalities. In a previous study, we identified variation in the use of
      transcutaneous electrical nerve stimulation (TENS), low level laser or
      acupuncture, massage and weight reduction advice for patients with knee OA. The
      purpose of this study was to examine factors that might explain variation in
      treatment modalities for patients with knee OA. METHODS: Practising
      physiotherapists prospectively collected data for one patient with knee
      osteoarthritis each through 12 treatment sessions.We chose to examine factors
      that might explain variation in the choice of treatment modalities supported by
      high or moderate quality evidence, and modalities which were frequently used but
      which were not supported by evidence from systematic reviews. Experienced
      clinicians proposed factors that they thought might explain the variation in the
      choice of these specific treatments. We used these factors in explanatory
      analyses. RESULTS: Using TENS, low level laser or acupuncture was significantly
      associated with having searched databases to help answer clinical questions in
      the last six months (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.08
      3.42). Not having Internet access at work and using more than four treatment
      modalities were significant determinants for giving massage (OR = 0.36, 95% CI =
      0.19-0.68 and OR = 8.92, 95% CI = 4.37-18.21, respectively). Being a female
      therapist significantly increased the odds for providing weight reduction advice
      (OR = 3.60, 95% CI = 1.12-11.57). No patient characteristics, such as age, pain
      or co-morbidity, were significantly associated with variation in practice.
      CONCLUSIONS: Factors related to patient characteristics, such as pain severity
      and co-morbidity, did not seem to explain variation in treatment modalities for
      patients with knee OA. Variation was associated with the following factors:
      physiotherapists having Internet access at work, physiotherapists having searched
      databases for the last six months and the gender of the therapist. There is a
      need for more studies of determinants for physiotherapy practice.

PMID- 20033889
TI  - Quantitative analysis of hydroxylated polymethoxyflavones by high-performance
      liquid chromatography.
AB  - Since the hydroxylated polymethoxyflavones were isolated from orange and other
      citrus peels, they have been found to exhibit potent anti-cancer and anti
      inflammatory activities. Hydroxylated polymethoxyflavones, especially 5
      demethylnobiletin and 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, exert more
      potent activities than their counterpart polymethoxyflavones (PMFs). These
      findings have led to a new era of exploration of hydroxylated polymethoxyflavones
      and PMFs from the citrus genus for their potential application in nutraceutical,
      pharmaceuticals and functional foods. A practical and efficient analytical method
      for quantitatively characterizing the composition of PMFs has only recently been
      developed, and has applications both in academic research laboratories and
      quality controls. However, chemical analyses of the hydroxylated
      polymethoxyflavones have not been previously described. This paper reports the
      quantitative analysis of six 5-demethylated PMFs in various commercial orange
      peel extracts, using high-performance liquid chromatography with UV detection.

PMID- 20033890
TI  - Development of an HPTLC-based diagnostic method for invasive aspergillosis.
AB  - A rapid, sensitive and specific high-performance thin-layer chromatographic
      (HPTLC) method was developed and validated for determination of gliotoxin in
      Aspergillus infected immunocompromised patients with invasive aspergillosis (IA).
      Densitometric analysis of gliotoxin was carried out in the absorbance mode at 254
      nm after single-step extraction with chloroform. The method uses TLC aluminum
      plates pre-coated with silica gel 60F-254 as a stationary phase and toluene
      isoamyl alcohol-methanol (10:0.5:0.5, v/v/v) as mobile phase, which gives compact
      spot of gliotoxin (R(f) = 0.51). The calibration curve was linear (r(2) > or =
      0.994) between peak area and concentration in the tested range of 100-1000 ng
      spot(-1) with minimum detectable range 0.025 ng mu(-1) of serum sample. The mean
      +/- SD value of slope and intercept of the standard chromatogram of gliotoxin
      were found to be 523.2 +/- 1.555635 and 915.8 +/- 30.68843, respectively. The
      developed method is simple, rapid, precise and less costly than earlier
      diagnostic methods, and different serum samples can be run on a single TLC plate
      for comparative analysis. The proposed method can be used to analyze gliotoxin in
      patient serum for easy, rapid and cost-effective diagnosis of IA.

PMID- 20033891
TI  - Validated LC-MS/MS assay for the quantitative determination of vardenafil in
      human plasma and its application to a pharmacokinetic study.
AB  - A sensitive high-performance liquid chromatography-tandem mass spectrometric
      (HPLC-MS/MS) assay has been developed for the quantitative analysis of vardenafil
      in human plasma. Vardenafil and the internal standard, alprazolam, were extracted
      from 0.2 mL aliquots of alkalinized plasma by a single solvent extraction into
      hexane : dichloromethane. Reversed-phase chromatographic separation was affected
      by gradient elution with mobile phases consisting of 10 mM ammonium formate pH
      7.0 (solvent A) and methanol (100%, solvent B), delivered at a flow rate of 0.4
      mL/min. The analytes were detected by using an electrospray ion source on a 4000
      QTrap triple quadrupole mass spectrometer operating in positive ionization mode.
      The mass transitions were m/z 489.3 --> 312.2 for vardenafil and m/z 309.2 -->
      281.0 for alprazolam. The assay was linear over the concentration range of 0.2
      100 ng/mL, with correlation coefficients > or = 0.995. The intra- and inter-day
      precision was less than 5.4% in terms of relative standard deviation and the
      accuracy was within 12.7% in terms of relative error. The lower limit of
      quantitation was set at 0.2 ng/mL. The high sensitivity and acceptable
      performance of the assay allowed its application to the analysis of plasma
      samples obtained following the oral administration of vardenafil to healthy male
      volunteers in a pharmacokinetic study.

PMID- 20033892
TI  - Simultaneous determination of peimine and peiminine in rat plasma by LC-ESI-MS
      employing solid-phase extraction.
AB  - A simple and reliable LC-ESI-MS method for the determination of peimine and
      peiminine in rat plasma was developed for the first time. The method was proven
      to be specific and sensitive by carrying out validation. The analytes were
      extracted from rat plasma via solid-phase extraction on Waters Oasis MCX
      cartridges. Chromatography separation was achieved on a C(18) column using 10 mM
      ammonium acetate (adjusted to pH 3.0 with glacial acetic acid)-acetonitrile
      (85:15, v/v) as mobile phase. The linear range was 1-100 ng/mL for peimine and
      peiminine. Intra- and inter-day precisiond were less than 10%. Accuracies were
      within 85-115% of their nominal concentrations. The limit of quantification was 1
      ng/mL for both analytes. The developed assay was successfully applied to
      pharmacokinetic study of peimine and peiminine in rats orally administered the
      alkaloids extracts from Bulbus Fritillariae, demonstrating a possible broader
      spectrum of applications of this method.

PMID- 20033893
TI  - Pasteurella multocida tracheobronchitis in a patient with CLL on rituximab.

PMID- 20033900
TI  - Traditional ELISA methods for antibody affinity determination fail to reveal the
      presence of low affinity antibodies in antisera: an alternative approach.
AB  - Traditionally used methods of antibody affinity determination either by ELISA or
      by the surface plasmon resonance technique do not allow detection of the presence
      of low-affinity antibodies in samples of high-affinity antibodies. In this paper
      we demonstrate the possibility to reveal their presence and to determine the
      affinities of both categories of antibodies as well as the ratio of their
      concentrations. This is especially important since by using traditional methods
      for antibody affinity evaluation the admixture of low-affinity antibodies in a
      sample diminishes the accuracy in determination of specific antibody affinity. In
      addition, the presence of an admixture of low-affinity antibodies may be an
      important biological characteristic of the system under study; their revelation
      and the evaluation of their binding parameters may be valuable in many cases for
      obtaining a more complete characterization of the binding properties of the
      multiple antibodies generated in an immune response.

PMID- 20033901
TI  - Brief problem-solving treatment in primary care (PST-PC) was not more effective
      than placebo for elderly patients screened positive of psychological problems.
AB  - OBJECTIVES: To evaluate whether screening followed by brief problem-solving
      treatment by primary care doctors (PST-PC) could improve health-related quality
      of life (HRQOL) and reduce consultation rates in the elderly. DESIGN: A single
      blind randomized placebo controlled trial (RCT). SETTING: Two government funded
      primary care clinics in Hong Kong. PARTICIPANTS: Two hundred and ninety nine
      Chinese patients aged 60 years or over, with positive screening scores for
      psychological problems by the Hospital Anxiety and Depression Scale (HADS).
      INTERVENTIONS: One hundred and forty nine subjects were randomized to receive
      brief PST-PC from primary care doctors (treatment) and 150 to group video-viewing
      (placebo). All subjects were followed up by telephone at 6, 12, 26 and 52 weeks.
      MAIN OUTCOME MEASURES: Changes in SF-36 HRQOL scores, HADS scores and monthly
      consultation rates were compared within and between groups. RESULTS: Study
      completion rates were 69-71%. There was significant improvement in the SF-36 role
      emotional (RE) and mental component summary (MCS) scores at week 6 in the PST-PC
      group but not in the placebo group. Several SF-36 scores improved significantly
      in the placebo (video) group at week 6-52. Mixed effects analysis adjusting for
      baseline values and cofounders did not show any difference in any of the outcomes
      between the PST-PC and placebo (video) groups. CONCLUSIONS: Screening followed by
      brief PST-PC was associated with a short-term improvement in HRQOL in Chinese
      elderly patients screened positive of psychological problems, but the HRQOL
      benefit was not greater than those found in the placebo group who participated in
      group-viewings of health education videos.

PMID- 20033902
TI  - Subjective well-being, social support, and age-related functioning among the very
      old in China.
AB  - OBJECTIVE: Previous research has suggested that social support and functional
      status influence the subjective well-being of the elderly. However, few studies
      have investigated whether these associations influence well-being in the very
      old. METHODS: In this population-based, cross-sectional study, 1401 persons aged
      90 years or over were located in Du Jiang Yan city, Sichuan, China. Among them
      732 were willing to participate and provided data on a battery of standardized
      questionnaire inventories. The 23-item Philadelphia Geriatric Center Morale Scale
      (PGCMS) was examined as an index of subjective well-being. Functional status was
      assessed using the physical self-maintenance scale (PSMS) and the instrumental
      activities of daily living (IADL) scales. The mini-mental state examination
      (MMSE) was used to measure cognitive function. Social support was assessed using
      the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR) scale
      and the social support requirement scale (SSRS). RESULTS: The mean age was 93.7
      +/- 3.4 years for the participants, of whom 68% were female. PGCMS total scores
      were significantly correlated with the Family APGAR and Objective Support
      subscale of the SSRS, as well as with scores on the MMSE and PSMS scales.
      However, in a multiple regression analysis, only MMSE and Family APGAR scores
      were independent predictors of PGCMS scores. CONCLUSION: Both social support from
      family members and cognitive function appear to be key factors associated with
      quality of life among the very old in China. Further research is needed among
      very old populations to confirm the importance of these variables and to examine
      potential cross-cultural differences.

PMID- 20033903
TI  - Awareness of carer distress in people with dementia.
AB  - OBJECTIVES: People caring for family members who have dementia often experience
      considerable levels of anxiety and depression. However, relatively little is
      known about the awareness of carer distress among people with dementia. This
      study investigated whether or not people with dementia are aware of the level of
      distress experienced by their carers. METHOD: Two groups of participants were
      studied, a dementia group and a control group of people with arthritis. Each
      group consisted of pairs of people, the person with dementia or arthritis and the
      family member who acted as their main carer; 40 pairs participated in total. For
      both groups, the carer's psychological health was rated by the carer themselves
      and by the care-recipient, using the Hospital Anxiety and Depression Scale. For
      the dementia group, memory functioning in the person with dementia was rated by
      the care-recipient themselves and by the carer, using the Memory Function Scale.
      The ratings made by the carer and care-recipient were compared to give an
      indication of the level of awareness in the care-recipient. RESULTS: People with
      dementia have a significant level of awareness of their carers' state of
      psychological health. Their awareness follows the same pattern as that shown by a
      control group of people with arthritis. The level of awareness of carer
      psychological health shown by the dementia group was not related to their level
      of awareness of their own memory difficulties. CONCLUSION: The clinical
      implications of awareness of carer distress in people with dementia should be
      considered.

PMID- 20033904
TI  - Chronic endurance exercise training prevents aging-related cognitive decline in
      healthy older adults: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effects of endurance exercise training (EET) on the
      cognitive status of healthy community-dwelling older adults. METHODS: A
      randomized controlled trial was conducted involving community-dwelling older
      adults from the town of Pianoro (northern Italy). We randomized 120 healthy
      subjects aged 65-74 years, both genders, to treatment (N = 60) and control (N =
      60) groups. The treatment consisted of 12 months of supervised EET in a community
      gym, 3 h a week. All participants were assessed both at baseline and after 12
      months on an intention-to-treat analysis. Cognitive status was assessed by one
      single test (Mini Mental State Examination, MMSE). Anthropometric indexes,
      routine laboratory measurements and C-reactive protein (CRP) were also assessed.
      RESULTS: The control group showed a significant decrease in MMSE score (mean
      difference -1.21, 95% CI -1.83/-0.60, p = 0.0002), which differed significantly
      (p = 0.02) from the treatment group scores (-0.21, 95% CI -0.79/0.37, p = 0.47).
      The odds ratio for the treated older adults to have a stable cognitive status
      after 1 year, as compared to the control group, was 2.74 (95% CI 1.16/6.48) after
      adjustment for age, gender, educational level and several other possible
      confounders. Blood pressure, body mass index, waist circumference and serum
      cholesterol did not differ significantly between the two groups, while CRP
      decreased only in the treatment group. CONCLUSIONS: A 12-month EET intervention
      may reduce the progression of age-related cognitive decline in healthy older
      adults.

PMID- 20033905
TI  - Depression and anxiety in chronic heart failure and chronic obstructive pulmonary
      disease: prevalence, relevance, clinical implications and management principles.
AB  - OBJECTIVE: To review evidence regarding the prevalence, causation, clinical
      implications, aspects of healthcare utilisation and management of depression and
      anxiety in chronic heart failure and chronic obstructive pulmonary disease.
      DESIGN: A critical review of the literature (1994-2009). FINDINGS: The prevalence
      of depression and anxiety is high in both chronic obstructive pulmonary disease
      (8-80% depression; 6-74% anxiety) and chronic heart failure (10-60% depression;
      11-45% anxiety). However, methodological weaknesses and the use of a wide range
      of diagnostic tools make it difficult to reach a consensus on rates of
      prevalence. Co-morbid depression and anxiety are associated with increased
      mortality and healthcare utilisation and impact upon functional disability and
      quality of life. Despite these negative consequences, the identification and
      management of co-morbid depression and anxiety in these two diseases is
      inadequate. There is some evidence for the positive role of pulmonary/cardiac
      rehabilitation and psychotherapy in the management of co-morbid depression and
      anxiety, however, this is insufficient to guide recommendations. CONCLUSIONS: The
      high prevalence and associated increase in morbidity and mortality justifies
      future research regarding the management of anxiety and depression in both
      chronic heart failure and chronic obstructive pulmonary disease. Current evidence
      suggests that multi-faceted interventions such as pulmonary and cardiac
      rehabilitation may offer the best hope for improving outcomes for depression and
      anxiety.

PMID- 20033907
TI  - The effect of dopamine partial agonists on the nicotine dependency in patients
      with schizophrenia.
AB  - OBJECTIVE: We compared the effects of haloperidol and three atypical
      antipsychotics (risperidone, olanzapine, and aripiprazole) on nicotine dependence
      in schizophrenic patients. METHODS: One hundred and thirty nine schizophrenic
      patients, who began using antipsychotic medication, were assessed for severity of
      nicotine dependence and for cigarette craving at baseline and following 8 weeks
      of treatment using the Fagerstrom Tolerance Questionnaire (FTQ) and a Likert
      style, seven point, visual-analogue rating scale. RESULTS: Nicotine dependence
      increased in the haloperidol group, but not in atypical antipsychotics groups.
      Patients treated with aripiprazole showed a reduction both in nicotine dependence
      and cigarette craving. CONCLUSIONS: The effects of aripiprazole, a partial
      agonist of the dopamine D2 receptor, may reduce the severity of nicotine
      dependence in schizophrenic patients.

PMID- 20033906
TI  - Metabolic, pathologic, and genetic analysis of prostate tissues: quantitative
      evaluation of histopathologic and mRNA integrity after HR-MAS spectroscopy.
AB  - The impact of high-resolution magic angle spinning (HR-MAS) spectroscopy on the
      histopathologic and mRNA integrity of human prostate tissues was evaluated. Forty
      prostate tissues were harvested at transrectal ultrasound (TRUS) guided biopsy (n
      = 20) or radical prostatectomy surgery (n = 20), snap-frozen on dry ice, and
      stored at -80 degrees C until use. Twenty-one samples (n = 11 biopsy, n = 10
      surgical) underwent HR-MAS spectroscopy prior to histopathologic and cDNA
      microarray analysis, while 19 control samples (n = 9 biopsy, n = 10 surgical)
      underwent only histopathologic and microarray analysis. Frozen tissues were
      sectioned at 14-um intervals and placed on individual histopathology slides.
      Every 8th slide was stained with hematoxylin and eosin (H&E) and used to target
      areas of predominantly epithelial tissue on the remaining slides for mRNA
      integrity and cDNA microarray analysis. Histopathologic integrity was graded from
      1 (best) to 5 (worst) by two 'blinded' pathologists. Histopathologic integrity
      scores were not significantly different for post-surgical tissues (HR-MAS vs
      controls); however, one pathologist's scores were significantly lower for biopsy
      tissues following HR-MAS while the other pathologist's scores were not. mRNA
      integrity assays were performed using an Agilent 2100 Bioanalyzer and the
      electrophoretic traces were scored with an RNA integrity number (RIN) from 1
      (degraded) to 10 (intact). RIN scores were not significantly different for
      surgical tissues, but were significantly lower for biopsy tissues following HR
      MAS spectroscopy. The isolated mRNA then underwent two rounds of amplification,
      conversion to cDNA, coupling to Cy3 and Cy5 dyes, microarray hybridization,
      imaging, and analysis. Significance analysis of microarrays (SAM) identified no
      significantly over- or under-expressed genes, including 14 housekeeping genes,
      between HR-MAS and control samples of surgical and biopsy tissues (5% false
      discovery rate). This study demonstrates that histopathologic and genetic
      microarray analysis can be successfully performed on prostate surgical and biopsy
      tissues following HR-MAS analysis; however, biopsy tissues are more fragile than
      surgical tissues.

PMID- 20033908
TI  - The association between concurrent psychotropic medications and self-reported
      adherence with taking a mood stabilizer in bipolar disorder.
AB  - OBJECTIVE: Multiple psychotropic medications are routinely prescribed to treat
      bipolar disorder, creating complex medication regimens. This study investigated
      whether the daily number of psychotropic medications or the daily number of pills
      were associated with self-reported adherence with taking a mood stabilizer.
      METHODS: Patients self-reported their mood and medications taken daily for about
      6 months. Adherence was defined as taking at least one pill of any mood
      stabilizer daily. Univariate general linear models (GLMs) were used to estimate
      if adherence was associated with the number of daily medications and the number
      of pills, controlling for age. The association between mean daily dosage of mood
      stabilizer and adherence was also estimated using a GLM. RESULTS: Three hundred
      and twelve patients (mean age 38.4 +/- 10.9 years) returned 58,106 days of data
      and took a mean of 3.1 +/- 1.6 psychotropic medications daily (7.0 +/- 4.2
      pills). No significant association was found between either the daily number of
      medications or the daily number of pills and adherence. For most mood
      stabilizers, patients with lower adherence took a significantly smaller mean
      daily dosage. CONCLUSIONS: The number of concurrent psychotropic medications may
      not be associated with adherence in bipolar disorder. Patients with lower
      adherence may be taking smaller dosages of mood stabilizers.

PMID- 20033909
TI  - Early communication of drug safety concerns: a feasibility study on enhancing
      interaction between the pharmaceutical industry and regulators.
AB  - PURPOSE: The responsibility for monitoring the safety of marketed medicines is
      shared between regulatory authorities and the pharmaceutical industry and is
      underpinned by legal obligations on both sides. Both marketing authorisation
      holders (MAHs) and regulators initially evaluate and investigate potential safety
      concerns, and then work together on further review as appropriate. We wanted to
      test the feasibility of enhanced interaction between MAH and regulator via a
      regular monthly, two-way communication of potential safety concerns between the
      MAHs and the Medicines and Healthcare Products Regulatory Agency (MHRA). It was
      envisaged that such a process would aid prioritisation and planning by both
      parties, avoid duplication of effort and support a collaborative approach for
      decision making. METHODS: Four MAHs took part in the pilot, which was conducted
      between July 2007 and June 2008. Potential safety concerns were exchanged on a
      monthly basis. The MAH/MHRA proposed a timeline for evaluation of each potential
      safety concern. The pilot did not include serious public health issues which are
      immediately reported to regulatory authorities. RESULTS: During the pilot, 136
      potential safety concerns were exchanged. Thirteen per cent of these resulted in
      a change to product information for health professionals and patients. There was
      concurrence between the MAHs and MHRA on timelines proposed for evaluation.
      CONCLUSIONS: The pilot proved feasible for the companies involved and indicated
      potential benefits of a system for avoiding duplication of effort and supporting
      a collaborative approach to planning and prioritisation of investigation of
      potential safety concerns between pharmaceutical industry and regulatory
      authorities.

PMID- 20033910
TI  - Adverse drug events among children presenting to a hospital emergency department
      in Newfoundland and Labrador, Canada.
AB  - OBJECTIVES: The aim of this study was to examine epidemiologic characteristics of
      Adverse Drug Events (ADEs) among children and adolescents presenting to an
      Emergency Department (ED) in Newfoundland and Labrador (NL), Canada. MATERIALS
      AND METHODS: This study was conducted in three phases and included an ED chart
      review of visits to the Janeway Hospital in St. John's, NL, between 27th April
      2006 and 26th April 2007. The first phase narrowed the sampling frame by
      excluding visits highly unlikely to be drug-related. In the second phase, a
      random sample of ED charts was selected for review by two research nurses using a
      Trigger Assessment Tool that classified ED visits according to their likelihood
      of being drug related ('high', 'moderate', 'low', 'very low', or 'no'
      probability). The third phase included a full chart review of all 'high',
      'moderate', 'low', and 'very low' probability ADE charts, carried out
      independently by two ED pediatricians and two clinical pharmacists. Each ADE was
      also scored for severity and preventability, and consensus was reached among all
      four reviewers during meetings held at the end of this phase. RESULTS: In this
      study, 69 patients presented to the ED either due to an ADE or a possible ADE
      (PADE). After a sample-weight adjustment, the prevalence of ADEs/PADEs was found
      to be 2.1%. The number of co-morbidities was inversely associated with medication
      related visits. There was no significant difference found between patients with
      and without medication related visits with respect to mean age of the patient and
      the mean number of current medications being taken. Of the 69 confirmed
      ADE/PADEs, none were fatal, six (8.7%) were serious/life-threatening, and 63
      (91.3%) were considered significant. Antimicrobial agents (45.0%) were the most
      common drug classes associated with ADEs/PADEs. Approximately 20% of the 69
      ADEs/PADEs identified were considered preventable. CONCLUSIONS: In St. John's NL,
      emergency department visits as a result of ADEs are common among the pediatric
      population and in many cases preventable. Age and number of current medications
      do not appear to be associated with ED visits related with ADE. Antimicrobial
      agents were found to be to the cause of most ADEs/PADEs.

PMID- 20033911
TI  - Hospital pharmacists' knowledge and opinions regarding adverse drug reaction
      reporting in Northern China.
AB  - PURPOSE: This study was designed to investigate the knowledge and opinions of
      hospital pharmacists about the spontaneous reporting of adverse drug reactions
      (ADRs) in Inner Mongolia, a northern region of China. METHODS: A face-to-face
      questionnaire survey of hospital pharmacists was conducted in five tertiary
      general hospitals in Inner Mongolia between July and December 2007. The
      structured questionnaire consisted of questions about the demographic details of
      the pharmacists, their knowledge of pharmacovigilance and their opinions on
      pharmacists' involvement in ADR reporting. RESULTS: Of the 288 pharmacists
      visited, 246 responded giving a total response rate of 85.4%. An amount of 70% of
      the pharmacists could define ADR correctly and 78.0% knew how to report ADRs.
      However, only one-third were clear as to what should be reported. The majority of
      pharmacists (92.7%) considered ADR reporting to be a professional obligation.
      However, only 36 (14.6%) claimed to have reported an ADR in their career, 25 of
      these 36 pharmacists (69.4%) were clinical pharmacists. Younger pharmacists and
      those who had received ADR training were more likely to report an ADR. The three
      major reasons for not reporting were: uncertain association (81.9%), insufficient
      clinical knowledge (68.6%) and lack of time (45.7%). The most frequently
      mentioned suggestion for improvement included more education on ADR reporting
      (66.7%), participation in ward rounds (43.9%) and encouragement from the pharmacy
      department (32.9%). CONCLUSION: Our investigation showed hospital pharmacists in
      a northern region of China had a reasonable knowledge of and positive attitudes
      towards pharmacovigilance. However, the majority of pharmacists had never
      reported an ADR in their career. Pharmacists' ADR education and increasing
      involvement in patient care would be important in improving ADR reporting in
      hospitals.

PMID- 20033912
TI  - Force field-dependent structural divergence revealed during long time simulations
      of Calbindin d9k.
AB  - The structural and the dynamic features of the Calbindin (CaB) protein in its
      holo and apo states are compared using molecular dynamics simulations under nine
      different force fields (FFs) (G43a1, G53a6, Opls-AA, Amber94, Amber99, Amber99p,
      AmberGS, AmberGSs, and Amber99sb). The results show that most FFs reproduce
      reasonably well the majority of the experimentally derived features of the CaB
      protein. However, in several cases, there are significant differences in
      secondary structure properties, root mean square deviations (RMSDs), root mean
      square fluctuations (RMSFs), and S(2) order parameters among the various FFs.
      What is more, in certain cases, these parameters differed from the experimentally
      derived values. Some of these deviations became noticeable only after 50 ns. A
      comparison with experimental data indicates that, for CaB, the Amber94 shows
      overall best agreement with the measured values, whereas several others seem to
      deviate from both crystal and nuclear magnetic resonance data.

PMID- 20033913
TI  - Prediction of interactiveness between small molecules and enzymes by combining
      gene ontology and compound similarity.
AB  - Determination of whether a small organic molecule interacts with an enzyme can
      help to understand the molecular and cellular functions of organisms, and the
      metabolic pathways. In this research, we present a prediction model, by combining
      compound similarity and enzyme similarity, to predict the interactiveness between
      small molecules and enzymes. A dataset consisting of 2859 positive couples of
      small molecule and enzyme and 286,056 negative couples was employed. Compound
      similarity is a measurement of how similar two small molecules are, proposed by
      Hattori et al., J Am Chem Soc 2003, 125, 11853 which can be availed at
      http://www.genome.jp/ligand-bin/search_compound, while enzyme similarity was
      obtained by three ways, they are blast method, using gene ontology items and
      functional domain composition. Then a new distance between a pair of couples was
      established and nearest neighbor algorithm (NNA) was employed to predict the
      interactiveness of enzymes and small molecules. A data distribution strategy was
      adopted to get a better data balance between the positive samples and the
      negative samples during training the prediction model, by singling out one-fourth
      couples as testing samples and dividing the rest data into seven training
      datasets-the rest positive samples were added into each training dataset while
      only the negative samples were divided. In this way, seven NNAs were built.
      Finally, simple majority voting system was applied to integrate these seven
      models to predict the testing dataset, which was demonstrated to have better
      prediction results than using any single prediction model. As a result, the
      highest overall prediction accuracy achieved 97.30%.

PMID- 20033914
TI  - Basic ingredients of free energy calculations: a review.
AB  - Methods to compute free energy differences between different states of a
      molecular system are reviewed with the aim of identifying their basic ingredients
      and their utility when applied in practice to biomolecular systems. A free energy
      calculation is comprised of three basic components: (i) a suitable model or
      Hamiltonian, (ii) a sampling protocol with which one can generate a
      representative ensemble of molecular configurations, and (iii) an estimator of
      the free energy difference itself. Alternative sampling protocols can be
      distinguished according to whether one or more states are to be sampled. In cases
      where only a single state is considered, six alternative techniques could be
      distinguished: (i) changing the dynamics, (ii) deforming the energy surface,
      (iii) extending the dimensionality, (iv) perturbing the forces, (v) reducing the
      number of degrees of freedom, and (vi) multi-copy approaches. In cases where
      multiple states are to be sampled, the three primary techniques are staging,
      importance sampling, and adiabatic decoupling. Estimators of the free energy can
      be classified as global methods that either count the number of times a given
      state is sampled or use energy differences. Or, they can be classified as local
      methods that either make use of the force or are based on transition
      probabilities. Finally, this overview of the available techniques and how they
      can be best used in a practical context is aimed at helping the reader choose the
      most appropriate combination of approaches for the biomolecular system,
      Hamiltonian and free energy difference of interest.

PMID- 20033915
TI  - The function and regulation of TBX22 in avian frontonasal morphogenesis.
AB  - The frontonasal mass gives rise to the facial midline and fuses with the
      maxillary prominence to form the upper lip. Here we focus on the regulation and
      function of TBX22, a repressor dynamically expressed in the frontonasal mass.
      Both FGF and Noggin (a BMP antagonist) strongly induce gTBX22, however, each has
      opposite effects on morphogenesis - Noggin inhibits whereas FGF stimulates
      growth. To determine whether TBX22 mediates these effects, we used retroviruses
      to locally increase expression levels. RCAS::hTBX22 decreased proliferation,
      reduced expression of MSX2 and DLX5 and caused cleft lip. Decreased levels of
      endogenous gTBX22 were also observed but were not the primary cause of the
      phenotype as determined in rescue experiments. Our data suggest that genetic or
      environmental insults such as those affecting the BMP pathway could lead to a
      gain-of-function of TBX22 and predispose an individual to cleft lip.

PMID- 20033916
TI  - The use of tetradecanoylphorbol acetate-stimulated peripheral blood cells
      enhances the prognostic value of interphase fluorescence in situ hybridization in
      patients with chronic lymphocytic leukemia.
AB  - Interphase fluorescence in situ hybridization (I-FISH) studies have a remarkable
      prognostic value in patients with chronic lymphocytic leukemia (CLL). I-FISH
      studies can be performed either on tetradecanoylphorbol acetate stimulated
      peripheral blood cells (I-FISH-TPA) or unstimulated peripheral blood mononuclear
      cells (I-FISH-PBMC). The aim of the study was to evaluate whether this finding
      was clinically relevant in a group of 235 patients with CLL. Fifty-six patients
      had both I-FISH-TPA and I-FISH-PBMC results. Compared with uncultured cells, the
      cytogenetic detection rate rose from 57 to 80% with the use of TPA-stimulated
      cells (P = 0.014). I-FISH-TPA provided a better prediction of treatment-free
      survival compared with I-FISH-PBMC (P = 0.031 vs. 0.166). Then, I-FISH-PBMC
      results from 93 historical patients were compared with 86 recent patients with I
      FISH-TPA results. Genomic aberrations were detected in 46 and 67% of patients
      from the I-FISH-PBMC and I-FISH-TPA cohorts, respectively. The detection rate of
      13q deletion as the only aberration increased from 10% with I-FISH-PBMC to 37%
      with I-FISH-TPA (P = 0.006). In conclusion, I-FISH-TPA increased the detection
      rate of 13q deletion and had an improved prognostic value compared with I-FISH
      PBMC.

PMID- 20033917
TI  - Synanthropic primates in Asia: potential sentinels for environmental toxins.
AB  - Macaques are similar to humans both physiologically and behaviorally. In South
      and Southeast Asia they are also synanthropic, ecologically associated with
      humans. Synanthropy with humans raises the possibility that macaques come into
      contact with anthropogenic toxicants, such as lead and mercury, and might be
      appropriate sentinels for human exposures to certain toxic materials. We measured
      lead (Pb) and mercury (Hg) levels and characterized the stable isotopic
      compositions of delta(15)N and delta(13)C in hair from three groups of free
      ranging macaques at the Swoyambhu temple in Kathmandhu, Nepal, an urban
      population that has abundant contact with humans. Hair lead levels were
      significantly higher among young macaques and differed among the three groups of
      macaques that were sampled. Hair Hg levels were low. No statistical association
      was found between stable isotopic compositions (delta(15)N and delta(13)C) and Pb
      and Hg levels. Our data did not find evidence that lead levels were associated
      with diet. We conclude that, in this population of macaques, behavioral and/or
      physiologic factors may play a significant role in determining exposure to lead.
      Chemical analysis of hair is a promising, noninvasive technique for determining
      exposure to toxic elements in free-ranging nonhuman primates.

PMID- 20033918
TI  - Brief communication: Captive gorillas are right-handed for bimanual feeding.
AB  - Predominance of right-handedness has historically been considered as a hallmark
      of human evolution. Whether nonhuman primates exhibit population-level manual
      bias remains a controversial topic. Here, we investigated the hypothesis that
      bimanual coordinated activities may be a key-behavior in our ancestors for the
      emergence and evolution of human population-level right-handedness. To this end,
      we collected data on hand preferences in 35 captive gorillas (Gorilla gorilla)
      during simple unimanual reaching and for bimanual coordinated feeding. Unimanual
      reaching consisted of grasping food on the ground, while bimanual feeding
      consisted of using one hand for holding a food and processing the food item by
      the opposite hand. No population-level manual bias was found for unimanual
      actions but, in contrast, gorillas exhibited a significant population-level right
      handedness for the bimanual actions. Moreover, the degree of right-handedness for
      bimanual feeding exceeds any other known reports of hand use in primates,
      suggesting that lateralization for bimanual feeding is robust in captive
      gorillas. The collective evidence is discussed in the context of potential
      continuity of handedness between human and nonhuman primates.

PMID- 20033921
TI  - Paternity and social rank in wild chimpanzees (Pan troglodytes) from the Budongo
      Forest, Uganda.
AB  - We analyzed patterns of paternity and male dominance rank in the Sonso community
      of wild East African chimpanzees (Pan troglodytes schweinfurthii) in the Budongo
      Forest, Uganda. Our major objective was to determine whether and how social rank
      influenced paternity success. We successfully genotyped 52 individuals at up to
      nine microsatellite loci, using DNA extracted from fecal samples. Of 24 offspring
      analyzed, we identified sires for 21. Paternity success was significantly
      correlated with social rank, with alpha males siring a disproportionate number of
      offspring. However, both middle- and low-ranking males also fathered offspring,
      and the priority-of-access model provided a relatively poor prediction of which
      males would be successful and under what circumstances. The concentration of
      paternities among only seven males and the tendency for high-ranking males to
      sire offspring of multiparous females suggest that both individual variation in
      male quality and the resource value of particular females may be mediating
      factors. In comparison with other chimpanzee studies, our results support the
      hypothesis that larger male cohort size reduces the ability of the alpha male to
      monopolize females, though within our study, male number did not affect the
      success of the alpha. Successful sires were not necessarily those who achieved
      the highest mating success with the females whose offspring they sired, but were
      those who demonstrated higher investment by spending significantly more time in
      association with these females. Finally, we estimate extra-group paternity at 0
      5%, supporting other evidence that the community serves as the primary
      reproductive unit in chimpanzees.

PMID- 20033922
TI  - Determinates of underutilization of amniocentesis among Israeli Arab women.
AB  - OBJECTIVES: To study the determinants of amniocentesis underutilization among
      Israeli Arab Muslim women. METHODS: Pregnant women referred for amniocentesis (n
      = 476) were identified through family health centers (FHCs). Data on
      sociodemographic characteristics, knowledge of prenatal testing, and attitudes
      toward termination of pregnancy (TOP) were collected through interviews and from
      medical records. RESULTS: Of all women eligible for amniocentesis free of charge,
      only 17.9% (95% CI: 14.7-21.6) underwent the test. Women referred as a result of
      advanced maternal age underwent the test less often than those referred for other
      indications [13.5% and 25.0%, respectively, (p = 0.002)]. In multivariate
      analyses, determinants for amniocentesis underutilization among women referred
      for advanced maternal age were: being religious [OR 2.71 (95% CI 1.04-7.01)],
      perceiving amniocentesis a risky procedure [OR 3.25 (95% CI 1.28-8.20)], spouse's
      opposing TOP [OR 3.73 (95% CI 1.48-9.37)], less advanced age [OR 0.74 (95% CI
      0.58-0.94)] and being a housewife [OR 2.59 (95% CI 0.96-6.95)]. In women referred
      for other reasons poor accessibility [OR 5.49 (95% CI 1.50-20.05)], perceiving
      amniocentesis a risky procedure [OR 3.45 (95% CI 1.17-10.17)] and spouse's
      opposing TOP [OR 7.47 (95% CI 2.46-22.63)] were the significant determinants.
      CONCLUSIONS: Any program aimed at increasing amniocentesis uptake among Muslim
      women should be directed to both partners and should emphasize the low risk for
      miscarriage following the test.

PMID- 20033923
TI  - Chitosan-based hydrogels do not induce angiogenesis.
AB  - The aim of this study was to assess the angiogenic potential of chitosan-glycerol
      phosphate (GP)-hydroxyethyl cellulose (HEC) binder for injectable bone tissue
      engineering applications. The angiogenic response of chitosan-GP-HEC combined
      with and without human bone marrow-derived mesenchymal stem cells (hMSCs) was
      examined using the chick chorioallantoic membrane (CAM) assay. Chitosan-GP-HEC
      gel did not show any angiogenic potential, whereas the presence of hMSCs gave
      rise to an enhanced angiogenic response when placed on the CAM for 3 days.
      Quantitatively, significantly more blood vessel formation was observed for the
      stem cell-containing group as compared to all other groups (p < 0.05), except for
      the b-FGF-positive control. The results indicate that the chitosan-GP-HEC binder
      does not contribute to enhanced angiogenesis and that the presence of hMSCs
      enhances angiogenesis.

PMID- 20033924
TI  - Direct visual control on cord coagulation using a fetoscopy-guided bipolar
      forceps. Description of a new technique.
AB  - OBJECTIVE: We describe a new technique to achieve permanent umbilical cord
      occlusion. METHODS: A 3 mm in diameter bipolar diathermy forceps was built to
      house a 1.2 mm fetoscope, emerging between the blades of the forceps. The device
      can be inserted percutaneously through a 10 Fr Trocar into the amniotic cavity
      under local analgesia and ultrasound guidance. A monochorionic (MC) twin
      pregnancy with a twin reversed arterial perfusion sequence at 18 weeks of
      gestation underwent cord occlusion of the acardiac twin using this new device in
      2004. RESULTS: The instrument allowed cord coagulation under direct visual
      control. The pregnancy continued until 33 weeks of gestation when a male infant
      of 1980 g was delivered by cesarean section following preterm labor. CONCLUSION:
      This new instrument might allow easier access to the cord and reduce operation
      time by direct visualization of the target and, therefore, improve the outcome
      after the procedure.

PMID- 20033925
TI  - Mesenchymal stem cell function on hybrid organic/inorganic microparticles in
      vitro.
AB  - The aim of this study was to investigate mesenchymal stem cell (MSC) function on
      novel type hybrid organic/inorganic microparticles (MPs) for application to bone
      regeneration. The MPs were based on chitosan (CS) and consisted of inorganic
      components, such as dibasic calcium phosphate (CaHPO(4)) or calcium carbonate
      (CaCO(3)). The MPs were crosslinked using tripolyphosphate. Four types of hybrid
      MPs were fabricated: CS; CS-10% CaHPO(4); CS-20% CaHPO(4); and CS-10% CaCO(3).
      The MSCs were attached to all the types of MPs at day 1 and started to spread and
      proliferate further by days 2 and 7, as analysed by fluorescence microcopy. Cell
      proliferation was measured at days 7, 14, 21 and 28 by counting the cells
      attached on the MPs. The number of proliferated cells increased significantly for
      all types of MPs as time increased. MSC differentiation was analysed using
      osteoblast (OB) phenotype markers, including alkaline phosphatase activity (ALP),
      collagen I (COLLI) and osteocalcin (OCN) at days 7, 14, 21 and 28, using
      quantitative real-time PCR. The normalized mRNA expression of ALP for all MPs was
      observed only at day 7. The normalized mRNA expression of COLLI and OCN was
      significantly increased for all types of hybrid MPs at each time point compared
      to the control samples. Collectively, our results proved that hybrid
      organic/inorganic MPs were non-cytotoxic and supported MSC attachment, spreading,
      proliferation and differentiation into the OB phenotype. These hybrid MPs have
      great potential for application as bone-void fillers or bone tissue engineering
      scaffolds in bone regeneration.

PMID- 20033926
TI  - Timing, rather than the concentration of cyclic AMP, correlates to osteogenic
      differentiation of human mesenchymal stem cells.
AB  - Previously, we demonstrated that protein kinase A (PKA) activation using
      dibutyryl-cAMP in human mesenchymal stem cells (hMSCs) induces in vitro
      osteogenesis and bone formation in vivo. To further investigate the physiological
      role of PKA in hMSC osteogenesis, we tested a selection of G-protein-coupled
      receptor ligands which signal via intracellular cAMP production and PKA
      activation. Treatment of hMSCs with parathyroid hormone, parathyroid hormone
      related peptide, melatonin, epinephrine, calcitonin or calcitonin gene-related
      peptide did not result in accumulation of cAMP or induction of alkaline
      phosphatase (ALP) expression. The only ligand that did induce cAMP, prostaglandin
      E2, even inhibited ALP expression and mineralization, suggesting that
      physiological levels of cAMP may inhibit osteogenesis. Furthermore, intermittent
      exposure of hMSCs to dibutyryl-cAMP inhibited ALP expression, whereas we did not
      observe an inhibitive effect at low dibutyryl-cAMP concentrations. Taken
      together, our results demonstrate that cAMP can either stimulate or inhibit
      osteogenesis in hMSCs, depending on the duration, rather than the strength, of
      the signal provided.

PMID- 20033927
TI  - The effect of PKC activation and inhibition on osteogenic differentiation of
      human mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) are being considered for several areas of
      clinical therapy, due to their multipotent nature. For instance, osteogenic hMSCs
      are applied in bone tissue engineering, but current differentiation protocols
      need further optimization before they can be clinically applied. Protein kinase C
      (PKC) family members have been implicated in bone metabolism, which prompted us
      to use a pharmaceutical approach to manipulate PKC signalling in hMSCs.
      Inhibition of PKC resulted in a dose-dependent inhibition of dexamethasone
      induced osteogenic differentiation. Surprisingly, PKC activation using phorbol 12
      myristate 13-acetate (PMA) also resulted in inhibition of osteogenesis, although
      we observed that inhibition was more pronounced at low than at high
      concentrations of PMA. Furthermore, we observed that inhibition of PKCdelta
      blocked alkaline phosphatase (ALP, an early marker of osteogenic differentiation)
      expression, whereas inhibition of the conventional PKC subfamily and PKCmicro
      using Go6976 resulted in an induction of ALP activity, collagen (I) expression
      and mineralization. In conclusion, inhibition of the conventional PKCs/PKCmicro
      and activation of PKCdelta could further benefit osteogenic differentiation of
      hMSCs in vitro and in vivo, which is currently under investigation.

PMID- 20033928
TI  - Cytokine stimulation and the choice of promoter are critical factors for the
      efficient transduction of mouse T cells with HIV-1 vectors.
AB  - BACKGROUND: HIV-1 fails to successfully infect mouse T cells as a result of
      several blocks in the viral replication cycle. We investigated whether this also
      impacted on the use of HIV-1 derived lentiviral vectors for stable gene transfer
      into mouse T cells. METHODS: Freshly isolated primary mouse T cells were
      immediately mixed with lentiviral vectors encoding an enhanced green fluorescent
      protein marker gene and transduction frequency was determined after 5 days of
      culture. RESULTS: Optimal transduction required both mouse T cell activation and
      cytokine support. Furthermore, transduction was also dependent upon the promoter
      chosen, with the rank order of potency being PGK > EF1 > SFFV > CMV. HIV-1
      lentiviral vectors also efficiently transduced cytokine-stimulated T cells (in
      the absence of antibody driven T cell activation), albeit with a lower level of
      transgene expression compared to fully-activated T cells. CONCLUSIONS: The
      present study demonstrates that primary mouse T cells can be efficiently
      transduced with HIV-1 lentiviral vectors, opening up prospects for their use in
      mouse models of gene-modified adoptive cellular therapy.

PMID- 20033929
TI  - Collision-induced dissociation mass spectra of glucosinolate anions.
AB  - Collision-induced dissociation (CID) mass spectra of differently substituted
      glucosinolates were investigated under negative-ion mode. Data obtained from
      several glucosinolates and their isotopologues ((34)S and (2)H) revealed that
      many peaks observed are independent of the nature of the substituent group. For
      example, all investigated glucosinolate anions fragment to produce a product ion
      observed at m/z 195 for the thioglucose anion, which further dissociates via an
      ion/neutral complex to give two peaks at m/z 75 and 119. The other product ions
      observed at m/z 80, 96 and 97 are characteristic for the sulfate moiety. The
      peaks at m/z 259 and 275 have been attributed previously to glucose 1-sulfate
      anion and 1-thioglucose 2-sulfate anion, respectively. However, based on our
      tandem mass spectrometric experiments, we propose that the peak at m/z 275
      represents the glucose 1-thiosulfate anion. In addition to the common peaks, the
      spectrum of phenyl glucosinolate (beta-D-Glucopyranose, 1-thio-, 1-[N
      (sulfooxy)benzenecarboximidate] shows a substituent-group-specific peak at m/z
      152 for C(6)H(5)-C(=NOH)S(-), the CID spectrum of which was indistinguishable
      from that of the anion of synthetic benzothiohydroxamic acid. Similarly, the m/z
      201 peak in the spectrum of phenyl glucosinolate was attributed to C(6)H(5)
      C(=S)OSO(2)(-).

PMID- 20033931
TI  - Single-molecule FRET imaging for enzymatic reactions at high ligand
      concentrations.

PMID- 20033930
TI  - Functional graphene oxide as a nanocarrier for controlled loading and targeted
      delivery of mixed anticancer drugs.
AB  - A simple synthetic route for the preparation of functional nanoscale graphene
      oxide (NGO), a novel nanocarrier for the loading and targeted delivery of
      anticancer drugs, is reported. The NGO is functionalized with sulfonic acid
      groups, which render it stable in physiological solution, followed by covalent
      binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically
      target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore,
      controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin
      (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic
      interactions is investigated. It is demonstrated that FA-NGO loaded with the two
      anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high
      cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that
      the combined use of two or more drugs, a widely adopted clinical practice, often
      displays much better therapeutic efficacy than that of a single drug, the
      controlled loading and targeted delivery of mixed anticancer drugs using these
      graphene-based nanocarriers may find widespread application in biomedicine.

PMID- 20033932
TI  - High-aspect-ratio imageable top-surface lithography using UV-assisted inkless
      contact printing.

PMID- 20033933
TI  - Simple and sensitive LC-ESI-MS method for the quantitation of sildenafil in
      plasma samples.
AB  - Sildenafil is a selective inhibitor of phosphodiesterase type 5 enzyme. A simple
      and sensitive LC-MS assay was developed to determine the concentration of
      sildenafil in human plasma. Sildenafil and omeprazole (internal standard) were
      extracted from the plasma with diethyl ether. The extract was evaporated under
      nitrogen and the residue was constituted with ACN and injected onto Novapak C(18)
      column (75x3.9 mm, 4 microm). The mobile phase consisted of 90% ACN plus 10%
      ammonium acetate (20 mM) containing 0.02% formic acid and was delivered
      isocratically at a flow rate of 0.2 mL/min. Sildenafil and omeprazole were
      monitored using a positive electrospray mode with single-ion recording set at m/z
      475 and 346, respectively, which are consistent with [M+H](+) molecular ions, and
      the run time was less than 5 min. The detection limit of sildenafil was 0.5
      ng/mL, and the calibration curve was linear between 0.5 and 2000 ng/mL
      (R(2)>0.99). Within- and between-day coefficients of variation were less than 7%.
      This method has been successfully used to measure sildenafil plasma
      concentrations in a beagle dog model following an oral administration of the
      drug.

PMID- 20033937
TI  - [Are we prepared? Highly contagious diseases].

PMID- 20033938
TI  - [Medicinal Chemistry of some "exotics". Agents against worm and protozoal
      diseases, and the antiviral ribavirin].

PMID- 20033943
TI  - [Antiviral strategies. Dengue and West Nile Virus].

PMID- 20033944
TI  - [Malaria is the most likely differential diagnosis. Fevers following tropical
      residence].

PMID- 20033946
TI  - [Tropical virus not only in the tropics. Treatment, epidemiology and diagnosis of
      tropical viral infections].

PMID- 20033949
TI  - [Unjustly neglected. Worm infestations].

PMID- 20033950
TI  - [Background information for consultation. Vaccinations in tropical and travel
      medicine].

PMID- 20033951
TI  - [Nobel Prize in Physiology and Medicine: famous endings].

PMID- 20033952
TI  - [Search for new drugs from natural sources. Marine sponges: cornucopia of the
      marine].

PMID- 20033953
TI  - [Staying healthy during travel is more than happiness. Travel pharmacy for the
      tropics].

PMID- 20033956
TI  - [Nobel Prize in Chemistry: Winning assembly line workers].

PMID- 20033961
TI  - [Passing the baton].

PMID- 20033965
TI  - [Emergency admission of peramivir in the U.S.A].

PMID- 20033967
TI  - PPh3-catalyzed reactions of alkyl propiolates with N-tosylimines: a facile
      synthesis of alkyl 2-[aryl(tosylimino)methyl]acrylate and an insight into the
      reaction mechanism.
AB  - A new PPh(3)-catalyzed synthesis of alkyl 2-[aryl(tosylimino)methyl]acrylates
      from propiolate and N-tosylimine has been developed. Deuterium-labelling
      experiments show that the reaction mechanism involves several hydrogen-transfer
      processes, which are not the turnover-limiting step and strongly rely on the
      nature of the reaction media. The stable phosphonium-enamine zwitterion, which
      was proven to play an important role in the catalytic cycle, has been isolated
      and characterised by X-ray analysis.

PMID- 20033966
TI  - An expeditious multigram-scale synthesis of lysine dendrigraft (DGL) polymers by
      aqueous N-carboxyanhydride polycondensation.
AB  - The synthesis and characterisation of new arborescent architectures of poly(L
      lysine), called lysine dendrigraft (DGL) polymers, are described. DGL polymers
      were prepared through a multiple-generation scheme (up to generation 5) in a
      weakly acidic aqueous medium by polycondensing N(epsilon)-trifluoroacetyl-L
      lysine-N-carboxyanhydride (Lys(Tfa)-NCA) onto the previous generation G(n-1) of
      DGL, which was used as a macroinitiator. The first generation employed
      spontaneous NCA polycondensation in water without a macroinitiator; this afforded
      low-molecular-weight, linear poly(L-lysine) G1 with a polymerisation degree of 8
      and a polydispersity index of 1.2. The spontaneous precipitation of the growing
      N(epsilon)-Tfa-protected polymer (GnP) ensures moderate control of the molecular
      weight (with unimodal distribution) and easy work-up. The subsequent alkaline
      removal of Tfa protecting groups afforded generation Gn of DGL as a free form
      (with 35-60% overall yield from NCA precursor, depending on the DGL generation)
      that was either used directly in the synthesis of the next generation (G(n+1)) or
      collected for other uses. Unprotected forms of DGL G1-G5 were characterised by
      size-exclusion chromatography, capillary electrophoresis and (1)H NMR
      spectroscopy. The latter technique allowed us to assess the branching density of
      DGL, the degree of which (ca. 25%) turned out to be intermediate between
      previously described dendritic graft poly(L-lysines) and lysine dendrimers. An
      optimised monomer (NCA) versus macroinitiator (DGL G(n-1)) ratio allowed us to
      obtain unimodal molecular weight distributions with polydispersity indexes
      ranging from 1.3 to 1.5. Together with the possibility of reaching high molecular
      weights (with a polymerisation degree of ca. 1000 for G5) within a few synthetic
      steps, this synthetic route to DGL provides an easy, cost-efficient, multigram
      scale access to dendritic polylysines with various potential applications in
      biology and in other domains.

PMID- 20033968
TI  - Size-tunable synthesis of monodisperse water-soluble gold nanoparticles with high
      X-ray attenuation.

PMID- 20033969
TI  - Transannular addition of phenols to 1,1'-dialkynylferrocenes: unanticipated
      formation of phenoxy[4]ferrocenophanedienes.
AB  - The reaction of some 1,1'-dialkynylferrocenes with a variety of phenols in the
      presence as well as in the absence of [Mo(CO)(6)] yields good to high yields of
      phenoxy[4]ferrocenophanedienes. Similar reactivity was observed with a thiophenol
      and with acetic acid. Reaction under basic reaction conditions led to the
      formation of the [4]ferrocenophanone 17. The phenoxy[4]ferrocenophanedienes
      obtained show dynamic behavior as a result of a torsional twist of the carbon
      bridge as indicated by the (1)H and (13)C NMR spectra. The reaction mechanism is
      discussed in view of recent related results of Sato et al. as well as of Pudelski
      et al. A vinyl cation intermediate is postulated in this context, whose relative
      stability is evident from the mass spectra of the compounds prepared.

PMID- 20033970
TI  - Chiral Bronsted acid directed iron-catalyzed enantioselective Friedel-Crafts
      alkylation of indoles with beta-aryl alpha'-hydroxy enones.
AB  - A cooperative catalytic system established by the combination of an iron salt and
      a chiral Bronsted acid has proven to be effective in the asymmetric Friedel
      Crafts alkylation of indoles with beta-aryl alpha'-hydroxy enones. Good to
      excellent yields and enatioselectivities were observed for a variety of alpha'
      hydroxy enones and indoles, particularly for the beta-aryl alpha'-hydroxy enones
      bearing an electron-withdrawing group at the para position of the phenyl ring (up
      to 90 % yield and 91 % ee). The proton of the chiral Bronsted acid, the Lewis
      acid activation site, as well as the inherent basic site for the hydrogen-bonding
      interaction of the Bronsted acid are responsible for the high catalytic
      activities and enantioselectivities of the title reaction. A possible reaction
      mechanism was proposed. The key catalytic species in the catalytic system, the
      phosphate salt of Fe(III), which was thought to be responsible for the high
      activity and good enantioselectivity, was then confirmed by ESIMS studies.

PMID- 20033971
TI  - Evidence for drug release from a metalla-cage delivery vector following cellular
      internalisation.

PMID- 20033972
TI  - Addition of carbene to the equator of C(70) to produce the most stable C(71)H(2)
      isomer: 2 aH-2(12)a-homo(C(70)-D(5h(6)))[5,6]fullerene.

PMID- 20033973
TI  - Functionally distinct modules operate two consecutive alpha,beta-->beta,gamma
      double-bond shifts in the rhizoxin polyketide assembly line.

PMID- 20033974
TI  - Cadmium imidazolate frameworks with polymorphism, high thermal stability, and a
      large surface area.

PMID- 20033975
TI  - Salt effects in the cononsolvency of poly(N-isopropylacrylamide) microgels.
AB  - Poly(N-isopropylacrylamide) (PNIPAM) is well known to exhibit reentrant behavior
      or cononsolvency in response to the composition of a mixed solvent consisting of
      water and a low-chain alcohol. Since the solvent structure plays an important
      role in this phenomenon, the presence of structure-breaking/structure-making ions
      in solution is expected to have a dramatic effect on the cononsolvency of PNIPAM.
      The present work examines the way that the presence of different salts can modify
      the reentrant-phase diagram displayed by a cationic PNIPAM microgel in the mixed
      ethanol/water solvent. The effects of four Hofmeister anions--SO(4)(2-), Cl(-),
      NO(3)(-) and SCN(-)--with different abilities to modify the solvent structure are
      analyzed. The species with kosmotropic or structure-making character show a clear
      competition with ethanol for the water molecules, intensifying the nonsolvency of
      the PNIPAM with the EtOH volume fraction (phi(e)). However, striking results are
      found with the most chaotropic or structure-breaking anion, SCN(-). In contrast
      to what happens in water-rich solutions, the presence of SCN(-) in alcohol-rich
      solvents enhances the solubility of the polymer, which macroscopically results in
      the microgel swelling. Moreover, this ion displays great stabilizing properties
      when phi(e)> is 0.2. These results have been explained by considering how
      chaotropic or structure-breaking ions interact with water and ethanol molecules.

PMID- 20033976
TI  - Physicochemical characterization of transport in nanosized membrane structures.
AB  - The understanding of polymer-solvent interactions is highly important for the
      development of tailored membrane manufacturing procedures and for the prediction
      of membrane performance from transport mechanisms. This study examines the
      permeation performance of organic solvents through state-of-the-art polyimide
      membranes (STARMEM, Membrane Extraction Technology Ltd.). Solvents are
      systematically selected to allow investigation of the effects of key
      physicochemical transport parameters by keeping constant all other parameters
      thought to be relevant. The effect of the solubility parameter, polarity
      (dielectric constant), surface tension, and viscosity are studied in detail. Dead
      end permeation experiments are carried out at 20 bar with STARMEM 122 and STARMEM
      240 membranes. Results for the selected solvents show higher permeation rates for
      ketones over alcohols and aromatics as well as for acids. It is suggested that
      the viscosity and polarity have a greater influence than the other parameters.
      The effect of solvent molar volume is also investigated. Transport of solvents
      with high molar volume, independent of their polarity and compatibility with the
      membrane material, is slower in all cases than for solvents with smaller molar
      volume. The solubility parameter does not show any significant effect on
      transport phenomena.

PMID- 20033977
TI  - Novel bottom-up SERS substrates for quantitative and parallelized analytics.
AB  - Surface-enhanced Raman spectroscopy (SERS) is an emerging technology in the field
      of analytics. Due to the high sensitivity in connection with specific Raman
      molecular fingerprint information SERS can be used in a variety of analytical,
      bioanalytical, and biosensing applications. However, for the SERS effect
      substrates with metal nanostructures are needed. The broad application of this
      technology is greatly hampered by the lack of reliable and reproducible
      substrates. Usually the activity of a given substrate has to be determined by
      time-consuming experiments such as calibration or ultramicroscopic studies. To
      use SERS as a standard analytical tool, cheap and reproducible substrates are
      required, preferably with a characterization technique that does not interfere
      with the subsequent measurements. Herein we introduce an innovative approach to
      produce low-cost and large-scale reproducible substrates for SERS applications,
      which allows easy and economical production of micropatterned SERS active
      surfaces on a large scale. This approach is based on an enzyme-induced growth of
      silver nanostructures. The special structural feature of the enzymatically
      deposited silver nanoparticles prevents the breakdown of SERS activity even at
      high particle densities (particle density >60%) that lead to a conductive layer.
      In contrast to other approaches, this substrate exhibits a relationship between
      electrical conductivity and the resulting SERS activity of a given spot. This
      enables the prediction of the SERS activity of the nanostructure ensemble and
      therewith the controllable and reproducible production of SERS substrates of
      enzymatic silver nanoparticles on a large scale, utilizing a simple measurement
      of the electrical conductivity. Furthermore, through a correlation between the
      conductivity and the SERS activity of the substrates it is possible to quantify
      SERS measurements with these substrates.

PMID- 20033978
TI  - Very low energy electrons transform the cyclobutane-pyrimidine dimer into a
      highly reactive intermediate.
AB  - Electrons with virtually no kinetic energy (close to 0 eV) trigger the
      decomposition of cytotoxic cyclobutane-pyrimidine dimer (CPD) into a surprisingly
      large variety of fragment ions plus their neutral counterparts. The response of
      CPD to low energy electrons is thus comparable to that of explosives like
      trinitrotoluene (TNT). The dominant unimolecular reaction is the splitting into
      two thymine like units, which can be considered as the essential molecular step
      in the photolyase of CPD. We find that CPD is significantly more sensitive
      towards low energy electrons than its thymine building blocks. It is proposed
      that electron attachment at very low energy proceeds via dipole bound states,
      supported by the large dipole moment of the molecule (6.2 D). These states act as
      effective doorways to dissociative electron attachment (DEA).

PMID- 20033979
TI  - Total synthesis confirms laetirobin as a formal Diels-Alder adduct.
AB  - Laetirobin, isolated from a parasitic fungus host-plant relationship, was
      synthesized in six practical steps with an overall yield of 12% from commercially
      available 2,4-dihydroxyacetophenone. Because the product is a pseudosymmetric
      tetramer of benzo[b]furans, each step of the synthesis was designed to involve
      tandem operations. Highlights include: 1) the double Sonogashira reaction of a
      bis(alkyne), 2) the practical copper(I)-mediated formation of a
      bis(benzo[b]furan), and 3) the biomimetic [4+2] dimerization and unexpected
      cationic [5+2] annulation of gem-diaryl alkene precursors. Preliminary structure
      activity relationship data between the isomeric [4+2] and [5+2] tetramers
      revealed only the natural product to possess promising anticancer potential.
      Specifically, laetirobin is capable of blocking tumor cell division (mitosis) and
      invoking programmed cell death (apoptosis).

PMID- 20033980
TI  - Diastereo- and enantioselective reductive aldol reaction with trichlorosilane
      using chiral Lewis bases as organocatalysts.

PMID- 20033981
TI  - Unusual interstrand Pt(S,S-diaminocyclohexane)-GG crosslink formed by
      rearrangement of a classical intrastrand crosslink within a DNA duplex.

PMID- 20033982
TI  - Hydrogen generation from formic acid decomposition with a ruthenium catalyst
      promoted by functionalized ionic liquids.

PMID- 20033983
TI  - High-intensity focused ultrasound for noninvasive functional neurosurgery.
AB  - Transcranial magnetic resonance (MR)-guided high-intensity focused ultrasound
      (tcMRgHIFU) implies a novel, noninvasive treatment strategy for various brain
      diseases. Nine patients with chronic neuropathic pain were treated with selective
      medial thalamotomies. Precisely located thermal ablations of 4mm in diameter were
      produced at peak temperatures of 51 degrees C to 60 degrees C under continuous
      visual MR guidance and MR thermometry. The resulting lesions are clearly visible
      on follow-up MR imaging. All treatments were well tolerated, without side effects
      or neurological deficits. This is the first report on successful clinical
      application of tcMRgHIFU in functional brain disorders, portraying it as safe and
      reliable for noninvasive neurosurgical interventions.

PMID- 20033985
TI  - Degeneration versus autoimmunity in multiple sclerosis.

PMID- 20033984
TI  - Role of endogenous testosterone concentration in pediatric stroke.
AB  - Previous studies have indicated a male predominance in pediatric stroke. To
      elucidate this gender disparity, total testosterone concentration was measured in
      children with arterial ischemic stroke (AIS; n = 72), children with cerebral
      sinovenous thrombosis (CSVT; n = 52), and 109 healthy controls. Testosterone
      levels above the 90th percentile for age and gender were documented in 10
      children with AIS (13.9%) and 10 with CSVT (19.2%), totaling 16.7% of patients
      with cerebral thromboembolism overall, as compared with only 2 of 109 controls
      (1.8%; p = 0.002). In multivariate analysis with adjustment for total cholesterol
      level, hematocrit, and pubertal status, elevated testosterone was independently
      associated with increased disease risk (odds ratio [95% confidence interval]:
      overall = 3.98 [1.38-11.45]; AIS = 3.88 [1.13-13.35]; CSVT = 5.50 [1.65-18.32]).
      Further adjusted analyses revealed that, for each 1nmol/l increase in
      testosterone in boys, the odds of cerebral thromboembolism were increased 1.3
      fold.

PMID- 20033986
TI  - Antibodies to native myelin oligodendrocyte glycoprotein in children with
      inflammatory demyelinating central nervous system disease.
AB  - OBJECTIVE: Myelin oligodendrocyte glycoprotein (MOG) is a candidate target
      antigen in demyelinating diseases of the central nervous system (CNS). Although
      MOG is encephalitogenic in different animal models, the relevance of this antigen
      in human autoimmune diseases of the CNS is still controversial. METHODS: We
      investigated the occurrence and biological activity of antibodies to native MOG
      (nMOG) in 47 children during a first episode of CNS demyelination (acute
      disseminated encephalomyelitis [ADEM], n = 19 and clinical isolated syndrome
      [CIS], n = 28) by a cell-based bioassay. RESULTS: High serum immunoglobulin G
      (IgG) titers to nMOG were detected in 40% of children with CIS/ADEM but 0% of the
      control children affected by other neurological diseases, healthy children, or
      adults with inflammatory demyelinating diseases, respectively. By contrast, IgM
      antibodies to nMOG occurred in only 3 children affected by ADEM. Children with
      high anti-nMOG IgG titer were significantly younger than those with low IgG
      titer. Anti-nMOG IgG titers did not differ between the ADEM and CIS group, and
      did not predict conversion from CIS to MS during a mean 2-year follow-up.
      However, intrathecal IgG anti-MOG antibody synthesis was only seen in CIS
      children. IgG antibodies to nMOG not only bound to the extracellular domain of
      nMOG, but also induced natural killer cell-mediated killing of nMOG-expressing
      cells in vitro. INTERPRETATION: Overall, these findings suggest nMOG as a major
      target of the humoral immune response in a subgroup of children affected by
      inflammatory demyelinating diseases of the CNS. Children may provide valuable
      insight into the earliest immune mechanisms of CNS demyelination.

PMID- 20033987
TI  - NEFL-related Charcot-Marie-tooth disease: an unraveling story.

PMID- 20033988
TI  - A sodium channel gene SCN9A polymorphism that increases nociceptor excitability.
AB  - Sodium channel Na(V)1.7, encoded by the SCN9A gene, is preferentially expressed
      in nociceptive primary sensory neurons, where it amplifies small depolarizations.
      In studies on a family with inherited erythromelalgia associated with Na(V)1.7
      gain-of-function mutation A863P, we identified a nonsynonymous single-nucleotide
      polymorphism within SCN9A in the affected proband and several unaffected family
      members; this polymorphism (c. 3448C&T, Single Nucleotide Polymorphisms database
      rs6746030, which produces the amino acid substitution R1150W in human Na(V)1.7
      [hNa(V)1.7]) is present in 1.1 to 12.7% of control chromosomes, depending on
      ethnicity. In this study, we examined the effect of the R1150W substitution on
      function of the hNa(V)1.7 channel, and on the firing of dorsal root ganglion
      (DRG) neurons in which this channel is normally expressed. We show that this
      polymorphism depolarizes activation (7.9-11mV in different assays). Current-clamp
      analysis shows that the 1150W allele depolarizes (6mV) resting membrane potential
      and increases ( approximately 2-fold) the firing frequency in response to
      depolarization in DRG neurons in which it is present. Our results suggest that
      polymorphisms in the Na(V)1.7 channel may influence susceptibility to pain.

PMID- 20033989
TI  - Influence of dominance status on adrenal activity and ovarian cyclicity status in
      captive African elephants.
AB  - The North American African (Loxodonta africana) elephant population is not self
      sustaining, in part because of a high rate of abnormal ovarian activity. About
      12% of adult females exhibit irregular cycles and 31% do not cycle at all. Our
      earlier work revealed a relationship between dominance status and ovarian
      acyclicity, with dominant females being more likely to not cycle normally. One
      theory is that dominant females may be expending more energy to maintaining peace
      within the captive herd than for supporting reproduction. The goal of this study
      was to determine if there was a relationship among dominance status, serum
      cortisol concentrations, and ovarian acyclicity. We hypothesized that adrenal
      glucocorticoid activity would be increased in dominant, noncycling elephants as
      compared with subdominant individuals. Blood samples were collected weekly over a
      2-year period in 81 females of known dominance and cyclicity status, and analyzed
      for cortisol. Based on a path analysis model (Reticular Action Model Or Near
      Approximation [RAMONA]), noncycling, dominant African elephant females did not
      have higher mean serum cortisol concentrations, or exhibit more variability
      (i.e., coefficient of variation, standard deviation) in cortisol secretion. This
      study suggests that alterations in adrenal activity are not related to dominance
      status nor contribute directly to acyclicity in captive African elephants.

PMID- 20033990
TI  - Captive-born intergeneric hybrid of a Guiana and bottlenose dolphin: Sotalia
      guianensis x Tursiops truncatus.
AB  - Bottlenose dolphins (Tursiops truncatus) and Guiana dolphin (Sotalia guianensis)
      live in sympatry along the Caribbean Coast of Central and South America and
      social interactions between these species have been described in the Caribbean
      Coast of Costa Rica, including sexual encounters. Here we examine and document
      the only known hybridization event between a male Guiana dolphin and a female
      bottlenose dolphin, in captivity at Oceanario Islas del Rosario (Colombian
      Caribbean), using photographic and genetic evidence from mitochondrial DNA
      markers and nuclear autosomal introns.

PMID- 20033991
TI  - Development of a flow cytometric co-immunoprecipitation technique for the study
      of multiple protein-protein interactions and its application to T-cell receptor
      analysis.
AB  - Co-immunoprecipitation is the classical approach for investigating protein
      protein interactions. Analysis is generally conducted using the Western blot
      approach. We set out to investigate whether flow cytometry was a feasible
      alternative to Western blotting. Using the TCR-CD3 complex as a model for
      intermolecular interactions in the MA5.8 cell line, FLAG-tagged CD3zeta-scFv
      fusion proteins could be captured on anti-FLAG coupled beads and associated
      TCRbeta molecules could be detected by flow cytometry. This association was
      abrogated by mutations to the CD3zeta transmembrane domain. Using multicolor flow
      cytometry, TCRbeta, CD3epsilon, and the scFv region of the CD3zeta fusion
      molecule could all be detected from a single sample. This multicolor analysis was
      then applied to demonstrate the importance of correct lysis conditions for
      extraction of the TCR complex. In summary, this flow cytometric
      immunoprecipitation technique is a feasible alternative to classical co
      immunoprecipitation analysis technique and offers many potential advantages
      including rapid analysis with increased target sensitivity, reduced technical
      demands, amenable to multiple protein analysis from a single sample, and provides
      a framework that may facilitate the development of high throughput analytical
      assays investigating protein-protein interactions.

PMID- 20033992
TI  - Prima facie.

PMID- 20033994
TI  - Role of quantitative assessment in fetal echocardiography.

PMID- 20033995
TI  - Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins.
AB  - Primary pulmonary hypoplasia is a rare, usually lethal, condition presenting only
      after birth without other congenital abnormalities. We describe the first case of
      fraternal twins diagnosed prenatally with primary pulmonary hypoplasia. Both had
      diffuse hypoplasia of the pulmonary arteries initially identified by fetal
      echocardiography and confirmed at autopsy following termination. These cases
      permit examination of the histopathology of this disease in the fetal stage of
      development.

PMID- 20033996
TI  - Prenatal diagnosis of isolated total anomalous systemic venous return to the
      coronary sinus.

PMID- 20033997
TI  - The 'starfish' sign: a novel sonographic finding with B-flow imaging and
      spatiotemporal image correlation in a fetus with total anomalous pulmonary venous
      return.

PMID- 20033998
TI  - Maternal obesity is a potential source of error in mid-trimester ultrasound
      estimation of gestational age.
AB  - OBJECTIVES: To investigate the possible impact of maternal obesity on
      ultrasonographic dating of pregnancy. METHODS: The Swedish Medical Birth Registry
      was used to identify 842 083 singleton pregnancies for which the estimated date
      of delivery (EDD) according to last menstrual period (EDD-LMP) and according to
      ultrasound examination (EDD-US) and maternal body mass index (BMI) in early
      pregnancy were known. Dates were adjusted following ultrasound examination,
      negative adjustment representing pregnancies that were shorter according to
      ultrasound examination than they were according to LMP. Odds ratios (OR) were
      adjusted for year of birth, maternal age, parity and smoking. RESULTS: The EDD
      was postponed at least 7 days (discrepancy between EDD-LMP and EDD-US of < or = 
      7 days) in 25.2% of all pregnancies. There was a statistically significant
      association between maternal BMI and discrepancy between EDD-LMP and EDD-US.
      Among pregnant women with a BMI > or = 30.0 kg/m(2), the risk of postponed EDD
      was significantly greater compared with women with a BMI of 20.0-24.9 kg/m(2).
      The EDD was more often postponed > or = 14 days (OR, 1.65; 95% CI, 1.60-1.70) or
      7-13 days (OR, 1.45; 95% CI, 1.42-1.48) among women with a BMI > or = 30 kg/m(2)
      than among women with normal weight. Similar risk was observed among women with a
      BMI of 25.0-29.9 kg/m(2), but was less pronounced. CONCLUSIONS: High maternal BMI
      increases the risk of postponing the EDD at mid-trimester ultrasound examination.

PMID- 20033999
TI  - Prevalence and perinatal outcome of dichorionic and monochorionic twins with
      nuchal translucency above the 99(th) percentile and normal karyotype.
AB  - OBJECTIVE: To evaluate the prevalence of and perinatal outcome associated with
      increased nuchal translucency thickness (NT) > 99(th) percentile in dichorionic
      and monochorionic twins with normal karyotype. METHODS: Two hundred and six
      consecutive twin pregnancies (166 dichorionic and 40 monochorionic) underwent an
      NT scan during a 4-year period. In those with NT > 99(th) percentile and normal
      karyotype, we performed first- and second-trimester anomaly scans, fetal
      echocardiography at 14-16 and 20-22 weeks, maternal serology and, in
      monochorionic pregnancies, serial ultrasound examinations every other week.
      Perinatal outcome was recorded. RESULTS: There were 10 (4.95%) pregnancies in
      which one of the fetuses had NT > 99(th) percentile and normal karyotype,
      including five fetuses (1.5%) in dichorionic and five (6.25%) in monochorionic
      pregnancies. During the same period the prevalence of NT > 99(th) percentile and
      normal karyotype in singleton pregnancies studied in our center was 2.6%. Among
      the 10 twins affected, six (60%) were diagnosed with structural abnormalities
      (three dichorionic and three monochorionic), and two intrauterine fetal demises
      occurred (one dichorionic and one monochorionic). Thus, the perinatal outcome was
      normal in only two of the pregnancies, one dichorionic and one monochorionic.
      CONCLUSIONS: The prevalence of NT > 99(th) percentile in dichorionic twins with a
      normal karyotype is similar to that in singletons. In monochorionic twins we
      confirmed previous studies reporting an increased prevalence compared with
      singletons. NT > 99(th) percentile with a normal karyotype in twins was
      associated with a high rate of fetal abnormalities and/or fetal demise (overall
      80%) irrespective of chorionicity.

PMID- 20034000
TI  - Cesarean section scar defects: agreement between transvaginal sonographic
      findings with and without saline contrast enhancement.
AB  - OBJECTIVES: To determine the agreement between transvaginal ultrasound
      examinations performed before and at saline contrast sonohysterography (SCSH)
      with regard to number, size and shape of Cesarean section (CS) scar defects.
      METHODS: In all, 108 women underwent transvaginal ultrasound examination with
      SCSH at least 6 months after CS: 68 had undergone one CS, 32 two CSs and eight
      women had undergone at least three CSs. The ultrasound examiner was blinded to
      the number of CSs and to the obstetric history. The number and shape of CS scar
      defects were determined subjectively, and any scar defect was estimated
      subjectively to be large or not large. Measurements of the scar defects were also
      taken. Results obtained before and at SCSH were compared. RESULTS: Most scar
      defects were triangular in shape. The shape did not change at SCSH, but the
      ultrasound examiner found it easier to delineate the borders of the scar defects
      at SCSH than at unenhanced ultrasound examination. More scar defects were seen
      and more scar defects were classified as large at SCSH than before: among the 100
      women who had undergone one or two CSs, 16 additional women had large defects at
      SCSH, whereas no woman with a large defect before SCSH had no defect or only a
      small defect at SCSH. The length and height of the defects were larger at SCSH
      than before: mean difference 2 mm and 1 mm in women who had undergone one CS, and
      mean difference 4 mm and 2 mm in the lowest-positioned scar in women who had
      undergone two CSs. CONCLUSIONS: In non-pregnant women CS scars were better
      evaluated at SCSH than at unenhanced ultrasound examination, because the
      demarcations of scar defects were more clearly delineated at SCSH than before.
      More defects were detected and more defects were classified as large at SCSH.

PMID- 20034001
TI  - Laparoscopy-assisted fetoscopy for laser surgery in twin-twin transfusion
      syndrome with anterior placentation.
AB  - OBJECTIVE: To compare a laparoscopy-assisted fetoscopic approach with an
      ultrasound-directed percutaneous approach for laser photocoagulation of placental
      anastomoses in cases of twin-twin transfusion syndrome (TTTS) with anterior
      placentation. METHOD: We performed a retrospective review of all cases that
      underwent laser ablation of placental anastomoses for TTTS with an anterior
      placenta at Texas Children's Fetal Center from November 2006 to November 2008.
      The two cohorts were identified by chart review based on the type of approach:
      laparoscopy-assisted vs. ultrasound-guided percutaneous uterine entry for
      fetoscopy. Operative and outcome data were extracted and the groups were compared
      using statistical methods, taking P < 0.05 as statistically significant. RESULTS:
      In the 100 cases of TTTS studied, 48 had an anterior placenta. Fifteen (31%) of
      these underwent laparoscopy-assisted fetoscopy (LAF) while a percutaneous
      approach was used in the remaining 33 (69%) cases. The total procedure time was
      longer in the LAF group than in the percutaneous group (96.1 +/- 25 vs. 67.9 +/-
      28 min; P < 0.01). There was no difference in the rate of preterm premature
      rupture of membranes up to 2 weeks and 4 weeks after surgery (7 vs. 15% and 13
      vs. 21%, for the LAF group vs. the percutaneous group, respectively; P = 0.7).
      The gestational ages at delivery were similar: 30.3 +/- 4.5 weeks in the LAF
      group and 29.2 +/- 4.6 weeks in the percutaneous group (P = 0.32). The overall
      survival rate at birth was tending towards better survival in the laparoscopic
      group than in the percutaneous group (80 vs. 61%, respectively; P = 0.06). The
      neonatal survival rate was better with the LAF approach than with the
      percutaneous approach (80 vs. 59%, respectively; P = 0.045). CONCLUSION:
      Laparoscopy-assisted entry of the uterus is associated with improved neonatal
      survival for laser photocoagulation in cases of TTTS with a complete anterior
      placentation.

PMID- 20034002
TI  - Unusual cardiac presentation of congenital cytomegalovirus infection.

PMID- 20034003
TI  - Macrosomia: a new formula for optimized fetal weight estimation.
AB  - OBJECTIVES: To develop and test a specific formula for estimating weight in the
      macrosomic fetus. METHODS: Ultrasound estimations of fetal weight were carried
      out within 1 week of delivery in 424 singleton fetuses with a birth weight of >
      or = 4000 g. Exclusion criteria were multiple pregnancy, intrauterine death and
      major structural or chromosomal anomalies. Stepwise regression modeling was used
      to derive a prediction formula with birth weight as the dependent variable and
      maternal booking weight and fetal biometric measurements as independent
      parameters. After a new formula for estimated fetal weight (EFW) had been
      developed in a formula-finding group (n = 284), it was compared with commonly
      used weight equations (evaluation group, n = 140). RESULTS: The new formula
      (log(e)EFW = 7.6377445039 + 0.0002951035 x maternal weight + 0.0003949464 x head
      circumference + 0.0005241529 x abdominal circumference + 0.0048698624 x femur
      length) proved to be superior to established equations, with the smallest mean
      error (mean +/- SD, -10 +/- 202 g), the smallest mean percentage error (mean +/-
      SD, -0.03 +/- 4.6%) and the lowest mean absolute percentage error (3.69 (range,
      0.05-13.57)%) when studied in the evaluation group. With the new formula, 77.9%
      of estimates fell within +/- 5% of the actual weight at birth, 97.1% within +/-
      10%, and 100% within +/- 15% and +/- 20%. CONCLUSIONS: The new formula allows
      better weight estimation in the macrosomic fetus.

PMID- 20034004
TI  - Hotelling's test, multiple t-tests, and uterine artery Doppler evaluation.

PMID- 20034006
TI  - Multispectral image analysis of binary encoded microspheres for highly
      multiplexed suspension arrays.
AB  - To push the 100-plex envelope of suspension array technology, we have developed
      fully automated methods to acquire multispectral images of multiplexed quantum
      dot (QD) encoded microspheres, to segment them in the images, to classify them
      based on their color code, and to quantify the multiplexed assays. Instead of
      coding microspheres with two colors and n levels, microspheres were coded with n
      colors and two levels (present or absent), thus transforming the classification
      problem from analog to digital. Images of multiplexed microspheres, sedimented at
      the bottom of microwells, were acquired through a tunable filter at the peak
      luminescence wavelength of each QD coding species in the system and the assay
      label wavelength. Another image of the light scattered from microspheres was
      captured in the excitation bandwidth that was utilized to localize microspheres
      in multispectral luminescence images. Objects in the acquired images are
      segmented and luminescence from each identified microsphere in each channel is
      recorded, based on which the "color code" of each microsphere is determined by
      applying a mathematical model and a classification algorithm. Our image analysis
      procedures could identify and classify microspheres with more than 97% accuracy,
      and the assay CVs were under 20%. These proof-of-principle results demonstrate
      that highly multiplexed quantification of specific proteins is possible with this
      rapid, small-sample volume format.

PMID- 20034007
TI  - Circulating tumor cells: determining its number and what it means.

PMID- 20034008
TI  - Prehistorical East-West admixture of maternal lineages in a 2,500-year-old
      population in Xinjiang.
AB  - As an area of contact between Asia and Europe, Central Asia witnessed a scenario
      of complex cultural developments, extensive migratory movements, and biological
      admixture between West and East Eurasians. However, the detanglement of this
      complexity of diversity requires an understanding of prehistoric contacts of the
      people from the West and the East on the Eurasia continent. We demonstrated the
      presence of genetic admixture of West and East in a population of 35 inhabitants
      excavated in Gavaerk in southern Xinjiang and dated 2,800-2,100 years before
      present by analyzing their mitochondrial DNA variations. This result indicates
      that the initial contact of the East and the West Eurasians occurred further east
      than Central Asia as early as 2,500 years ago.

PMID- 20034009
TI  - Brief communication: patterns of linkage disequilibrium and haplotype diversity
      at Xq13 in six Native American populations.
AB  - Comparative studies of linkage disequilibrium (LD) can provide insights into
      human demographic history. Here, we characterize LD in six Native American
      populations using seven microsatellite markers in Xq13, a region of the genome
      extensively studied in populations around the world. Native Americans show
      relatively low diversity and high LD, in agreement with recent genome-wide survey
      and a scenario of sequential founder effects accompanying human population
      dispersal around the globe. LD in Native Americans is similar to that observed in
      some recently described small population isolates and higher than in large
      European isolates (e.g., Finns), which have been extensively analyzed in medical
      genetics studies. Haplotype analyses are consistent with a colonization of the
      New World by a differentiated East Asian population, followed by extensive
      genetic drift in the Americas.

PMID- 20034011
TI  - Enthesopathies as occupational stress markers: evidence from the upper limb.
AB  - Enthesopathies--that is, "musculo-skeletal stress markers"--are frequently used
      to reconstruct past lifestyles and activity patterns. Relatively little attention
      has been paid in physical anthropology to methodological gaps implicit in this
      approach: almost all methods previously employed neglect current medical insights
      into enthesopathies and the distinction between healthy and pathological aspects
      has been arbitrary. This study presents a new visual method of studying
      fibrocartilaginous enthesopathies of the upper limb (modified from Villotte: Bull
      Mem Soc Anthropol Paris n.s. 18 (2006) 65-85), and application of this method to
      367 males who died between the 18th and 20th centuries, from four European
      identified skeletal collections: the Christ Church Spitalfields Collection, the
      identified skeletal collection of the anthropological museum of the University of
      Coimbra, and the Sassari and Bologna collections of the museum of Anthropology,
      University of Bologna. The analysis, using generalized estimating equations to
      model repeated binary outcome variables, has established a strong link between
      enthesopathies and physical activity: men with occupations involving heavy manual
      tasks have significantly (P-value < 0.001) more lesions of the upper limbs than
      nonmanual and light manual workers. Probability of the presence of an
      enthesopathy also increases with age and is higher for the right side compared
      with the left. Our study failed to distinguish significant differences between
      the collections when adjusted for the other effects. It appears that
      enthesopathies can be used to reconstruct past lifestyles of populations if
      physical anthropologists: 1) pay attention to the choice of entheses in their
      studies and 2) use appropriate methods.

PMID- 20034010
TI  - Genetic integration of molar cusp size variation in baboons.
AB  - Many studies of primate diversity and evolution rely on dental morphology for
      insight into diet, behavior, and phylogenetic relationships. Consequently,
      variation in molar cusp size has increasingly become a phenotype of interest. In
      2007 we published a quantitative genetic analysis of mandibular molar cusp size
      variation in baboons. Those results provided more questions than answers, as the
      pattern of genetic integration did not fit predictions from odontogenesis. To
      follow up, we expanded our study to include data from the maxillary molar cusps.
      Here we report on these later analyses, as well as inter-arch comparisons with
      the mandibular data. We analyzed variation in two-dimensional maxillary molar
      cusp size using data collected from a captive pedigreed breeding colony of
      baboons, Papio hamadryas, housed at the Southwest National Primate Research
      Center. These analyses show that variation in maxillary molar cusp size is
      heritable and sexually dimorphic. We also estimated additive genetic correlations
      between cusps on the same crown, homologous cusps along the tooth row, and
      maxillary and mandibular cusps. The pattern for maxillary molars yields genetic
      correlations of one between the paracone-metacone and protocone-hypocone.
      Bivariate analyses of cuspal homologues on adjacent teeth yield correlations that
      are high or not significantly different from one. Between dental arcades, the
      nonoccluding cusps consistently yield high genetic correlations, especially the
      metaconid-paracone and metaconid-metacone. This pattern of genetic correlation
      does not immediately accord with the pattern of development and/or calcification,
      however these results do follow predictions that can be made from the
      evolutionary history of the tribosphenic molar.

PMID- 20034012
TI  - Evidence of dietary differentiation among late Paleocene-early Eocene
      plesiadapids (Mammalia, primates).
AB  - Plesiadapis cookei is an extinct relative of extant euarchontans (primates,
      dermopterans; scandentians), which lived in North America during the late
      Paleocene. P. cookei body mass has been estimated to be approximately 2.2 kg,
      making it large compared with other species of its genus from North America, but
      similar to some from Europe. In particular, size as well as dental form
      similarities to P. russelli have been noted. However, it is thought that P.
      russelli evolved from P. tricuspidens, and into Platychoerops daubrei. Dental
      similarities among P. cookei, P. russelli, and P. daubrei have been hypothesized
      to reflect a more folivorous diet than utilized by P. tricuspidens. Here we test
      the hypothesis that P. cookei is more dietarily specialized than P. tricuspidens
      by quantifying functionally significant aspects of molar, premolar, and incisor
      forms. Casts of M(2)s and P(4)s of P. tricuspidens, P. cookei, and P. daubrei
      were microCT-scanned. We measured the relief index and/or the complexity from
      surface reconstructions of scans. Results show that P. cookei has higher M(2)
      relief and complexity than P. tricuspidens; P. daubrei exhibits the highest
      relief and complexity. Similarly, P. cookei has a more complex P(4) than P.
      tricuspidens, whereas that of P. daubrei exhibits the highest complexity.
      Finally, the I(1) of P. cookei resembles more the incisor of P. daubrei than that
      of P. tricuspidens. Because high relief and complexity of dentitions are related
      to fibrous plant diets in living mammals, these findings support the hypothesis
      that previously identified similarities among P. cookei, P. russelli and P.
      daubrei reflect a folivorous diet.

PMID- 20034013
TI  - Association of intronic polymorphism rs3773364 A>G in synapsin-2 gene with
      idiopathic epilepsy.
AB  - In epilepsy, there is a tendency towards recurrent unprovoked seizures. Seizures
      result due to the excessive electrical misfiring in the brain between neurons and
      disturbance in neurotransmitter release. Several gene products affect the
      behavior of these neurons by regulating neurotransmission via several mechanisms.
      One such gene, Synapsin-2 (SYN2), involved in synaptogenesis is also reported to
      regulate the neurotransmitter release. We hypothesized that SYN2 gene and its
      polymorphisms could affect the process of epileptogenesis and therapeutic
      response in humans. In this hospital-based study, we enrolled 372 patients with
      epilepsy and 199 control subjects. We selected rs3773364 A>G polymorphism in SYN2
      gene and analyzed its distribution in north Indian patients with epilepsy and
      control subjects. Genotyping was carried out by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) method. According to the
      results obtained, SYN2 "AG" genotype frequency was significantly higher in
      patients with epilepsy versus control subjects in north Indian population (P =
      0.02, OR = 1.55, 95% CI = 1.06-2.26). After subclassification, we observed higher
      frequency of AG genotype in idiopathic patients as compared to control subjects
      (P = 0.01, OR = 1.67, 95% CI = 1.08-2.56). There were no significant differences
      in genotypic (AG: OR = 0.80, P = 0.377; GG: P = 0.628, OR = 1.17) or allelic (P =
      0.86, OR = 1.03) frequency distributions in patients with multiple drug
      resistance versus patients with drug-responsive epilepsy. Results from our study
      indicate the involvement of SYN2 gene polymorphism in conferring risk to
      epilepsy; however, the genetic variant does not seem to modulate drug-response in
      epilepsy pharmacotherapy.

PMID- 20034014
TI  - Striatal dopamine D2 receptor availability predicts the thalamic and medial
      prefrontal responses to reward in cocaine abusers three years later.
AB  - Low levels of dopamine (DA) D2 receptor availability at a resting baseline have
      been previously reported in drug addicted individuals and have been associated
      with reduced ventral and dorsal prefrontal metabolism. The reduction in DA D2
      receptor availability along with the reduced ventral frontal metabolism is
      thought to underlie compromised sensitivity to nondrug reward, a core
      characteristic of drug addiction. We therefore hypothesized that variability in
      DA D2 receptor availability at baseline will covary with dynamic responses to
      monetary reward in addicted individuals. Striatal DA D2 receptor availability was
      measured with [(11)C]raclopride and positron emission tomography and response to
      monetary reward was measured (an average of three years later) with functional
      magnetic resonance imaging in seven cocaine-addicted individuals. Results show
      that low DA D2 receptor availability in the dorsal striatum was associated with
      decreased thalamic response to monetary reward; while low availability in ventral
      striatum was associated with increased medial prefrontal (Brodmann Area 6/8/32)
      response to monetary reward. These preliminary results, that need to be
      replicated in larger sample sizes and validated with healthy controls, suggest
      that resting striatal DA D2 receptor availability predicts variability in
      functional responses to a nondrug reinforcer (money) in prefrontal cortex,
      implicated in behavioral monitoring, and in thalamus, implicated in conditioned
      responses and expectation, in cocaine-addicted individuals.

PMID- 20034015
TI  - Passive rotation-induced theta rhythm and orientation homeostasis response.
AB  - Rhythmic oscillatory activities at the theta frequency (3-12 Hz) have long
      attracted attention, as they have been implicated in diverse brain functions.
      There are two kinds of hippocampal theta rhythms: Type 1 is an atropine-resistant
      noncholinergic theta rhythm, and Type 2 is an atropine-sensitive cholinergic
      theta rhythm. However, it has not yet been determined whether the theta rhythm
      generated during passive whole-body rotation is of Type 1 or 2. To clarify this
      issue, we investigated passive whole-body rotation-induced theta rhythm using
      C57BL/6J normal and atropine-treated mice. The results demonstrated that atropine
      [50 mg/kg, intraperitoneally (i.p.)], a cholinergic antagonist, abolished the
      theta rhythm generated during passive whole-body rotation. Therefore, the passive
      whole-body rotation-induced theta rhythm is an atropine-sensitive Type 2 theta
      rhythm. In addition, we found that blocking cholinergic receptors using atropine
      resulted in the loss of the orientation homeostasis response, which is a circling
      behavior in the direction opposite to that of the rotating circular treadmill
      that is generated to maintain a constant orientation. These results suggest that
      atropine-sensitive Type 2 theta rhythm can be generated by a passive rotation
      induced vestibular sensory signal and may be necessary for spatial orientation
      homeostasis response behavior.

PMID- 20034016
TI  - An experimental test of body volume constraint on female reproductive output.
AB  - The body volume constraint hypothesis is a widely accepted notion that explains
      proximate limitation of female reproductive output, but lacks empirical support.
      To examine how body volume determines reproductive output, we experimentally
      manipulated the body volume of female lacertid lizard (Takydromus
      septentrionalis), to examine whether a reduction in body volume caused a
      reduction in reproductive output. Clutch size and mass decreased with a reduction
      in body volume. Reproductive output (residual clutch mass, R(CM)) was negatively
      related to body volume reduction (BVR) (R(CM)=-0.008BVR+0.225). In contrast,
      neither egg size nor offspring size was affected by the manipulation. Relative
      clutch mass was lower in manipulated females than in control females, but the
      actual physical burden (egg plus pearls) carried by manipulated females was much
      bigger than that of the control females. A normal clutch of eggs only filled 55%
      of maternal body volume, whereas manipulated females used 75% of body volume to
      contain eggs and pearls. Therefore, females are capable of carrying more eggs
      than a normal clutch. Our observations provide unequivocal empirical support for
      the maternal body volume constraint hypothesis. In addition, these results
      suggest that female T. septentrionalis may produce a clutch of eggs that fill the
      available abdomen space to an optimal level rather than the physical limit.

PMID- 20034018
TI  - Observation and calculation of vibrational circular birefringence: a new form of
      vibrational optical activity.
AB  - We report the first mid-infrared observation of vibrational circular
      birefringence (VCB) arising from individual chiral molecules. VCB can also be
      called vibrational optical rotatory dispersion (VORD) and is the Kramers-Kronig
      transform of vibrational circular dichroism (VCD). The method of measurement
      involves a simple change in the optical set-up and electronic processing of a VCD
      spectrometer such that the VCB spectrum appears at twice the polarization
      modulation frequency as a pseudo vibrational linear dichroism (VLD) spectrum. VCB
      spectra are also calculated with density function theory (DFT) for the first time
      using a commercially available program for rotational strengths where the
      calculated intensities are convolved with the real, dispersive part of a
      normalized complex Lorentzian lineshape rather than the imaginary, absorptive
      part, normally used for IR and VCD intensity calculations. Comparison of the
      measured and calculated VCB, VCD, and IR spectra of (+)-R-limonene and (-)-S
      alpha-pinene show close agreement and confirm the validity of the new VCB
      measurements.

PMID- 20034017
TI  - Osthole or imperatorin-mediated facilitation of glutamate release is associated
      with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve
      endings.
AB  - Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson,
      have previously been shown to facilitate depolarization-evoked glutamate release
      from rat hippocampal nerve terminals by increasing voltage-dependent Ca(2+)
      entry. In this study, we further investigated whether osthole and imperatorin
      possess an action at the exocytotic machinery itself, downstream of a Ca(2+)
      influx. Our data showed that ionomycin-induced glutamate release and KCl-evoked
      FM1-43 release were facilitated by osthole and imperatorin, suggesting that some
      steps after Ca(2+) entry are regulated by these two compounds. Consistent with
      this, osthole or imperatorin-mediated facilitation of ionomycin-induced glutamate
      release was occluded by cytochalasin D that inhibits actin polymerization,
      implying that the disassembly of cytoskeleton is involved. In addition, the
      facilitatory action of osthole or imperatorin on ionomycin-induced glutamate
      release was attenuated by the Ca(2+)/calmodulin-dependent kinase II (CaMKII)
      inhibitor KN62. Furthermore, Western blotting analysis further showed that
      osthole or imperatorin significantly increased ionomycin-induced phosphorylation
      of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results
      suggest, therefore, that osthole or imperatorin-mediated facilitation of
      glutamate release involves modulation of downstream events controlling synaptic
      vesicle recruitment and exocytosis, possibly through an increase of CaMKII
      activation and synapsin I phosphorylation, thereby increasing synaptic vesicle
      availability for exocytosis.

PMID- 20034019
TI  - Skin peptides of different life stages of Ewing's tree frog.
AB  - In frogs, an important mechanism of skin innate immunity against invading
      microbial pathogens is secretion of antimicrobial peptides from the specialized
      granular glands. Since these glands develop fully in skin dermis after completion
      of metamorphosis, they are small and immature in skin of larvae (tadpoles). Skin
      secretions vary among different life stages. Antimicrobial activity and peptide
      composition of natural mixture of skin peptides of three different life stages of
      New Zealand Ewing's Tree Frog (Litoria ewingii), tadpoles, metamorphs and adults
      were analyzed. The peptide mixtures were collected from skin secretions and
      analyzed for activity against the standard reference bacterium, Escherichia coli
      (ATCC 25922). Their peptide components were analyzed using liquid chromatography
      mass spectrometry (LC-MS). The peptide mixture from adults and metamorphs
      contained the species-specific antimicrobial peptide uperin 7.1 and inhibited the
      growth of E. coli (ATCC 25922). In contrast, the peptide mixture of tadpoles did
      not inhibit the growth of E. coli (ATCC 25922). This peptide mixture did not
      contain uperin 7.1 but had peptides whose molecular masses did not correspond to
      molecular masses of any known frog antimicrobial peptides.

PMID- 20034020
TI  - Physical attachment of fluorescent protein particles to atomic force microscopy
      probes in aqueous media: implications for surface pH, fluorescence, and
      mechanical properties studies.
AB  - Transfer of a fluorescently labeled protein particle from a surface to a
      microsized scanning probe has been induced by repetitive scanning in aqueous
      medium. The so-attached particle can in turn act as a probing tool to study
      particle-substrate and particle-particle interactions. Attachment of the
      fluorescent particle occurs at the apical region of an atomic force microscope
      (AFM) cantilever tip and it endures repetitive loading-unloading cycles against
      the sample surface. Fluorescence microscopy has been used to address the exact
      location of the attached particle in the cantilever and to identify the moment
      when the particle contacts the sample. Moreover, we have observed that
      fluorescence intensity at the contact point is lower when the probing particle
      contacts another fluorescent particle than when it contacts the nonfluorescent
      substrate. The change in fluorescence is attributed to local changes of pH and
      interparticle-quenching of fluorophores in the contact region. These findings are
      promising since they constitute a chemical-free way to attach bioparticles to AFM
      probes under physiological conditions. The atomic force microscopy combined with
      fluorescence microscopy provides a straight forward method to study
      particle/particle and particle/substrate interactions, as well as to investigate
      mechanical properties of biocolloids.

PMID- 20034021
TI  - The use of Artificial Neural Networks to classify primate vocalizations: A pilot
      study on black lemurs.
AB  - The identification of the vocal repertoire of a species represents a crucial
      prerequisite for a correct interpretation of animal behavior. Artificial Neural
      Networks (ANNs) have been widely used in behavioral sciences, and today are
      considered a valuable classification tool for reducing the level of subjectivity
      and allowing replicable results across different studies. However, to date, no
      studies have applied this tool to nonhuman primate vocalizations. Here, we apply
      for the first time ANNs, to discriminate the vocal repertoire in a primate
      species, Eulemur macaco macaco. We designed an automatic procedure to extract
      both spectral and temporal features from signals, and performed a comparative
      analysis between a supervised Multilayer Perceptron and two statistical
      approaches commonly used in primatology (Discriminant Function Analysis and
      Cluster Analysis), in order to explore pros and cons of these methods in
      bioacoustic classification. Our results show that ANNs were able to recognize all
      seven vocal categories previously described (92.5-95.6%) and perform better than
      either statistical analysis (76.1-88.4%). The results show that ANNs can provide
      an effective and robust method for automatic classification also in primates,
      suggesting that neural models can represent a valuable tool to contribute to a
      better understanding of primate vocal communication. The use of neural networks
      to identify primate vocalizations and the further development of this approach in
      studying primate communication are discussed.

PMID- 20034022
TI  - Human immunodeficiency virus and hepatitis C infections induce distinct
      immunologic imprints in peripheral mononuclear cells.

PMID- 20034023
TI  - Is it difficult to obtain an optimal liver biopsy specimen?

PMID- 20034024
TI  - Liver injury in acute fatty liver of pregnancy: possible link to placental
      mitochondrial dysfunction and oxidative stress.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare disorder which is fatal if not
      recognized and treated early. Delivery of the feto-placental unit results in
      dramatic improvement in maternal liver function, suggesting a role for the
      placenta. However, the mechanisms by which defects in the fetus or placenta lead
      to maternal liver damage are not well understood and form the focus of this
      study. Placenta and serum were obtained at delivery from patients with AFLP, and
      placental mitochondria and peroxisomes were isolated. Placental mitochondrial
      function, oxidative stress, and fatty acid composition as well as serum
      antioxidants, oxidative and nitrosative stress markers, and fatty acid analysis
      were carried out. Hepatocytes in culture were used to evaluate cell death,
      mitochondrial function, and lipid accumulation on exposure to fatty acids.
      Oxidative stress was evident in placental mitochondria and peroxisomes of
      patients with AFLP, accompanied by compromised mitochondrial function. Increased
      levels of arachidonic acid were also seen in AFLP placenta when compared to
      control. Patients with AFLP also had a significant increase in oxidative and
      nitrosative stress markers in serum, along with decreased antioxidant levels and
      elevated levels of arachidonic acid. These levels of arachidonic acid were
      capable of inducing oxidative stress in hepatocyte mitochondria accompanied by
      induction of apoptosis. Exposure to arachidonic acid also resulted in increased
      lipid deposition in hepatocytes. CONCLUSION: Oxidative stress in placental
      mitochondria and peroxisomes is accompanied by accumulation of toxic mediators
      such as arachidonic acid, which may play a causative role in maternal liver
      damage seen in AFLP.

PMID- 20034025
TI  - Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and
      proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor
      growth in hepatitis B virus-positive hepatocellular carcinoma.
AB  - The ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region
      containing protein (ASPP) family of proteins regulates apoptosis through
      interaction with p53 and its family members. This study evaluated the epigenetic
      regulation of ASPP1 and ASPP2 in hepatitis B virus (HBV)-positive hepatocellular
      carcinoma (HCC) and explores the effects of down-regulation of ASPP1 and ASPP2 on
      the development of HCC. HCC cell lines and tissues from HCC patients were used to
      examine the expression and methylation of ASPP1 and ASPP2. The expression of
      ASPP1 and ASPP2 was diminished in HCC cells by epigenetic silence owing to
      hypermethylation of ASPP1 and ASPP2 promoters. Analyses of 51 paired HCC and
      surrounding nontumor tissues revealed that methylation of ASPP1 and ASPP2 was
      associated with the decreased expression of ASPP1 and ASPP2 in tumor tissues and
      the early development of HCC. Moreover, ASPP2 became methylated upon HBV x
      protein (HBx) expression. The suppressive effects on tumor growth by ASPP1 and
      ASPP2 were examined with RNA interference-mediated gene silence. Down-regulation
      of ASPP1 and ASPP2 promoted the growth of HCC cells in soft agar and in nude mice
      and decreased the sensitivity of HCC cells to apoptotic stimuli. CONCLUSION:
      ASPP1 and ASPP2 genes are frequently down-regulated by DNA methylation in HBV
      positive HCC, which may play important roles in the development of HCC. These
      findings provide new insight into the molecular mechanisms leading to
      hepatocarcinogenesis and may have potent therapeutic applications.

PMID- 20034026
TI  - Inhibition of poly adenosine diphosphate-ribose polymerase decreases
      hepatocellular carcinoma growth by modulation of tumor-related gene expression.
AB  - Hepatocellular carcinoma (HCC) is associated with a poor prognosis due to a lack
      of effective treatment options. In HCC a significant role is played by DNA damage
      and the inflammatory response. Poly (ADP-ribose) polymerase-1 (PARP-1) is an
      important protein that regulates both these mechanisms. The objective of this
      study was to examine the effect of pharmacology PARP-1 inhibition on the
      reduction of tumor volume of HCC xenograft and on the hepatocarcinogenesis
      induced by diethyl-nitrosamine (DEN). Pharmacologic PARP-1 inhibition with DPQ
      greatly reduces tumor xenograft volume with regard to a nontreated xenograft (394
      mm(3) versus 2,942 mm(3), P < 0.05). This observation was paralleled by
      reductions in xenograft mitosis (P = 0.02) and tumor vasculogenesis (P = 0.007,
      confirmed by in vitro angiogenesis study), as well as by an increase in the
      number of apoptotic cells in DPQ-treated mice (P = 0.04). A substantial
      difference in key tumor-related gene expression (transformed 3T3 cell double
      minute 2 [MDM2], FLT1 [vascular endothelial growth factor receptor-1, VEGFR1],
      epidermal growth factor receptor [EPAS1]/hypoxia-inducible factor 2 [HIF2A],
      EGLN1 [PHD2], epidermal growth factor receptor [EGFR], MYC, JUND, SPP1 [OPN],
      hepatocyte growth factor [HGF]) was found between the control tumor xenografts
      and the PARP inhibitor-treated xenografts (data confirmed in HCC cell lines using
      PARP inhibitors and PARP-1 small interfering RNA [siRNA]). Furthermore, the
      results obtained in mice treated with DEN to induce hepatocarcinogenesis showed,
      after treatment with a PARP inhibitor (DPQ), a significant reduction both in
      preneoplastic foci and in the expression of preneoplastic markers and
      proinflammatory genes (Gstm3, Vegf, Spp1 [Opn], IL6, IL1b, and Tnf),
      bromodeoxyuridine incorporation, and NF-kappaB activation in the initial steps of
      carcinogenesis (P < 0.05). CONCLUSION: This study shows that PARP inhibition is
      capable of controlling HCC growth and preventing tumor vasculogenesis by
      regulating the activation of different genes involved in tumor progression.

PMID- 20034029
TI  - Fluorescent in situ hybridization testing in primary sclerosing cholangitis:
      useful testing or a random chance result?

PMID- 20034030
TI  - Alcoholic liver disease.

PMID- 20034031
TI  - Lipidomic dissection of nonalcoholic steatohepatitis: moving beyond foie gras to
      fat traffic.

PMID- 20034032
TI  - IkappaB kinase epsilon: a potential therapeutic target for obesity (and
      nonalcoholic fatty liver disease)?

PMID- 20034033
TI  - Minocycline sensitizes rodent and human liver mitochondria to the permeability
      transition: implications for toxicity in liver transplantation.

PMID- 20034034
TI  - Hepatocytes from induced pluripotent stem cells: a giant leap forward for
      hepatology.

PMID- 20034036
TI  - N-acetylcysteine on its way to a broader application in patients with acute liver
      failure.

PMID- 20034037
TI  - A case of fulminant hepatic failure in pregnancy.

PMID- 20034038
TI  - Supporting evidence for natural killer T cell accumulation in progressive
      nonalcoholic fatty liver disease?

PMID- 20034040
TI  - An identification of the novel combination therapy for hepatitis C virus 1b
      infection by using a replicon system and human induced pluripotent stem cells.

PMID- 20034043
TI  - Diagnostic criteria for autoimmune hepatitis: what is the gold standard?

PMID- 20034045
TI  - Natural killer group 2 member D, its ligands, and liver disease: good or bad?

PMID- 20034046
TI  - Multifaceted perspective of the waiting list for liver transplantation: the value
      of pharmacokinetic models.

PMID- 20034047
TI  - Kupffer cell and interleukin-12-dependent loss of natural killer T cells in
      hepatosteatosis.
AB  - Hepatosteatosis is associated with increased expression of tumor necrosis factor
      alpha (TNF-alpha) and interleukin (IL)-12, major T helper (Th) 1 cytokines, and
      reduced hepatic natural killer T (NKT) cell numbers. The relationship between
      lipid accumulation, cytokine expression, and hepatic NKT cells is not known. This
      study was conducted to assess the role of IL-12 in the development of hepatic
      steatosis and its potential impact on liver NKT cells. Male C57Bl/6 wildtype (WT)
      and IL-12-deficient (IL-12(-/-)) mice were fed a choline-deficient diet (CDD) for
      0, 10, or 20 weeks. CDD led to marked hepatosteatosis, reduced hepatic but not
      splenic NKT cell numbers and function, and increased hepatic expression of the
      T(h)1-type cytokines IL-12, interferon gamma (IFN-gamma), and TNF-alpha in WT
      mice. The absence of IL-12 resulted in similar CDD-induced hepatosteatosis, but
      preserved hepatic NKT cells and significantly reduced hepatic IFN-gamma and TNF
      alpha expression. Treatment of CDD-fed mice with lipopolysaccharide led to a
      significant increase in hepatic IL-12 expression, and Kupffer cell (KC) depletion
      reduced liver IL-12 expression and restored NKT cells in CDD-induced fatty liver.
      Interestingly, KCs from CDD-fed mice failed to produce increased quantities of IL
      12 upon activation in vitro when compared to similarly treated KCs from control
      fed mice, suggesting that secondary factors in vivo promote heightened IL-12
      production. Finally, human livers with severe steatosis showed a substantial
      decrease in NKT cells. CONCLUSION: Hepatosteatosis reduces the numbers of hepatic
      NKT cells in a KC-and IL-12-dependent manner. Our results suggest a pivotal and
      multifunctional role of KC-derived IL-12 in the altered immune response in
      steatotic liver, a process that is likely active within human nonalcoholic fatty
      liver disease.

PMID- 20034050
TI  - Attacks on local persons by chimpanzees in Bossou, Republic of Guinea: long-term
      perspectives.
AB  - Attacks on humans by nonhuman primates are one of the most serious causes of
      human-primate conflict, and strongly influence people's perceptions and tolerance
      of nonhuman primates. Despite their importance, systematic and extensive records
      of such attacks are rare. Here, we report the attacks that occurred on local
      persons by chimpanzees (Pan troglodytes verus) at Bossou, Republic of Guinea,
      from 1995 to 2009. There have been a total of 11 attacks during this period, the
      majority of which were directed toward children. They varied in their severity,
      but all were nonfatal. Attacks took place on a road and narrow paths that
      bordered the forest or in cultivated fields and orchards where opportunities for
      human-chimpanzee contact are high. Attacks occurred between the months of March
      and October, coinciding with wild fruit scarcity, increased levels of crop
      raiding, and periods of human cultivation with likely increased human usage of
      paths. Although the families of attack victims felt angry and fearful toward
      chimpanzees after attacks, some drew on their traditional beliefs to explain why
      chimpanzees were respected, protected, and could not hurt them, even when attacks
      occurred. We provide suggestions for reducing future nonhuman primate attacks on
      humans in an effort to mitigate human-primate conflict situations.

PMID- 20034048
TI  - Protective effect of human leukocyte antigen B27 in hepatitis C virus infection
      requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope.
AB  - Human leukocyte antigen B27 (HLA-B27) is associated with protection in human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This
      protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell
      epitopes in both infections. In order to define the relative contribution of a
      specific HLA-B27-restricted epitope to the natural course of HCV infection, we
      compared the biological impact of the highly conserved HCV genotype 1 epitope,
      for which the protective role has been described, with the corresponding region
      in genotype 3 that differs in its sequence by three amino acid residues. The
      genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype
      1 peptide. Furthermore, patients with acute or chronic infection with HCV
      genotype 3a did not mount T-cell responses to this epitope region, and their
      autologous viral sequences showed no evidence of T-cell pressure. Finally, we
      found a significantly higher frequency of HLA-B27 positivity in patients with
      chronic HCV genotype 3a infection compared to genotype 1 infection, indicating
      that there is no protection by HLA-B27 in HCV genotype 3 infection. CONCLUSION:
      Our data indicate that the protective effect of HLA-B27 is limited to HCV
      genotype 1 infection and does not expand to other genotypes such as genotype 3a.
      This can most likely be explained by intergenotype sequence diversity leading to
      the loss of the immunodominant HLA-B27 epitope in viral strains other than
      genotype 1. Our results underline the central role of a single HLA-B27-restricted
      epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1
      infection.

PMID- 20034049
TI  - Increased caffeine consumption is associated with reduced hepatic fibrosis.
AB  - Although coffee consumption has been associated with reduced frequency of liver
      disease, it is unclear whether the effect is from coffee or caffeine and whether
      there is an effect on hepatic fibrosis specifically. This study was undertaken to
      use a food-frequency instrument for dietary caffeine consumption to evaluate the
      relationship between caffeine intake and liver fibrosis. Patients undergoing
      liver biopsy completed a detailed caffeine questionnaire on three occasions over
      a 6-month period. Caffeine intake was compared between patients with mild and
      advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was
      used to evaluate the association between caffeine consumption and hepatic
      fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with
      chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the
      caffeine questionnaire on up to three occasions. Results from repeated
      questionnaires were consistent. Daily caffeine consumption above the 75(th)
      percentile for the cohort (308 mg = approximately 2.25 cups of coffee
      equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33;
      95% confidence interval [CI], 0.14-0.80; P = 0.015) and the protective
      association persisted after controlling for age, sex, race, liver disease, body
      mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67; P =
      0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66; P
      = 0.009). Despite a modest trend, consumption of caffeine from sources other than
      coffee or of decaffeinated coffee was not associated with reduced liver fibrosis.
      A reliable tool for measurement of caffeine consumption demonstrated that
      caffeine consumption, particularly from regular coffee, above a threshold of
      approximately 2 coffee-cup equivalents per day, was associated with less severe
      hepatic fibrosis.

PMID- 20034051
TI  - p38 Mitogen-activated protein kinase signalling regulates vascular inflammation
      and epithelial barrier dysfunction in an experimental model of radiation-induced
      colitis.
AB  - BACKGROUND: : Microvascular injury and epithelial barrier dysfunction are rate
      limiting aspects in radiation enteropathy. This study examined the role of p38
      mitogen-activated protein kinase (p38 MAPK) signalling in radiation-induced
      colitis in an experimental model. METHODS: : The p38 MAPK inhibitor SB239063 was
      administered to mice immediately before exposure to 20 Gy radiation. Leucocyte-
      and platelet-endothelium interactions in the colonic microcirculation were
      assessed by intravital microscopy. Levels of myeloperoxidase (MPO) and CXC
      chemokines (macrophage inflammatory protein (MIP) 2 and cytokine-induced
      neutrophil chemoattractant (KC)), and albumin leakage were quantified 16 h after
      irradiation. RESULTS: : Irradiation induced an increase in leucocyte and platelet
      recruitment, MPO activity, CXC chemokine levels and intestinal leakage.
      Inhibition of p38 MAPK by SB239063 decreased radiation-induced leucocyte and
      platelet recruitment (leucocyte rolling and adhesion by 70 and 90 per cent, both
      P < 0.001; that of platelets by 70 and 74 per cent, both P < 0.001). It also
      reduced radiation-provoked increases in colonic MPO activity by 88 per cent (P <
      0.001), formation of MIP-2 and KC by 72 and 74 per cent respectively (P = 0.003
      and P < 0.001), and intestinal leakage by 81 per cent (P < 0.001). CONCLUSION: :
      p38 MAPK is an important signalling pathway in radiation-induced colitis.

PMID- 20034052
TI  - Hydrogen sulphide ameliorates ischaemia-reperfusion injury in an experimental
      model of non-heart-beating donor kidney transplantation.
AB  - BACKGROUND: : Therapies to alleviate ischaemia-reperfusion (IR) injury have an
      important role in kidney transplantation. This study used a porcine model of non
      heart-beating (NHB) donor kidneys to investigate the effects of hydrogen sulphide
      on IR injury. METHODS: : Porcine kidneys were subjected to 25 min of warm
      ischaemia and 18 h of cold storage. They were reperfused ex vivo with autologous
      oxygenated blood to assess renal function. A group treated with hydrogen sulphide
      (0.5 mmol/l) infused 10 min before and after reperfusion (n = 6) was compared
      with an untreated control group (n = 7). RESULTS: : Hydrogen sulphide
      significantly improved renal blood flow compared with control values (mean(s.d.)
      area under the curve (AUC) 614.9(165.5) versus 270.3(86.7) ml per min per 100
      g.h; P = 0.001) and renal function (AUC creatinine: 1640(248) versus 2328(154)
      micromol/l.h; P = 0.001; AUC creatinine clearance: 6.94(5.03) versus 0.96(0.32)
      ml per min per 100 g.h; P = 0.004). Oxidative damage was also reduced by hydrogen
      sulphide (urinary 8-isoprostane at 1 h of reperfusion: 478.9(237.1) versus
      1605.6(632.7) pg/ml per mmol/l creatinine; P = 0.032). CONCLUSION: : Hydrogen
      sulphide ameliorated the renal dysfunction associated with ischaemic damage, and
      has potential as a therapy against IR injury in NHB donor kidney transplantation.

PMID- 20034054
TI  - Medaka Oct4 is expressed during early embryo development, and in primordial germ
      cells and adult gonads.
AB  - Oct4 is a crucial transcription factor for controlling pluripotency in embryonic
      stem cells and the epiblast of mouse embryos. We have characterized the
      expression pattern of medaka (Oryzias latipes) Ol-Oct4 during embryonic
      development and in the adult gonads. Genomic analysis showed that Ol-Oct4 is the
      ortholog of zebrafish spg/pou2. However, their expression patterns are not the
      same, suggesting that Oct4 may play different roles in zebrafish and medaka.
      Using specific antibodies for the Ol-Oct4 protein, we showed that Ol-Oct4 is also
      expressed in primordial germ cells, in the spermatogonia (male germ stem cells),
      and during different stages of oocyte development. These results suggest that Ol
      Oct4 plays a post-embryonic role in the maturing gonads and gametes. The Ol-Oct4
      mRNA and protein expression patterns are similar to those of mammalian Oct4 and
      introduce medaka fish as a valid model for the functional and evolutionary study
      of pluripotency genes in vivo.

PMID- 20034053
TI  - Synaptic development of the mouse dorsal lateral geniculate nucleus.
AB  - The dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model
      system in the study of thalamic circuit development. However, there is still a
      lack of information regarding how and when various types of retinal and
      nonretinal synapses develop. We examined the synaptic organization of the
      developing mouse dLGN in the common pigmented C57/BL6 strain, by recording the
      synaptic responses evoked by electrical stimulation of optic tract axons, and by
      investigating the ultrastructure of identified synapses. At early postnatal ages
      (<P12), optic tract evoked responses were primarily excitatory. The full
      complement of inhibitory responses did not emerge until after eye opening (>P14),
      when optic tract stimulation routinely evoked an excitatory postsynaptic
      potential/inhibitory postsynaptic potential (EPSP/IPSP) sequence, with the latter
      having both a GABA(A) and GABA(B) component. Electrophysiological and
      ultrastructural observations were consistent. At P7, many synapses were present,
      but synaptic profiles lacked the ultrastructural features characteristic of the
      adult dLGN, and little gamma-aminobutyric acid (GABA) could be detected by using
      immunocytochemical techniques. In contrast, by P14, GABA staining was robust,
      mature synaptic profiles of retinal and nonretinal origin were easily
      distinguished, and the size and proportion of synaptic contacts were similar to
      those of the adult. The emergence of nonretinal synapses coincides with pruning
      of retinogeniculate connections, and the transition of retinal activity from
      spontaneous to visually driven. These results indicate that the synaptic
      architecture of the mouse dLGN is similar to that of other higher mammals, and
      thus provides further support for its use as a model system for visual system
      development.

PMID- 20034055
TI  - Genesis of rods in the zebrafish retina occurs in a microenvironment provided by
      polysialic acid-expressing Muller glia.
AB  - Polysialic acid (polySia) is a posttranslational modification of the neural cell
      adhesion molecule NCAM, which in the vertebrate brain is dynamically regulated
      during development and crucially involved in developmental and adult
      neurogenesis. In the fish retina, new neurons are persistently generated, but the
      possible contribution of polySia has not yet been addressed. Here we used
      immunohistochemistry with NCAM- and polySia-specific antibodies to study
      spatiotemporal expression patterns of NCAM and polySia in the developing and
      mature zebrafish retina. As early as 2.3 days postfertilization (dpf), NCAM but
      not polySia was detected on cell somata and fibers of the developing retina. At
      4.3 dpf polySia immunoreactivity first appeared in the ventral retina and was
      localized to the nascent outer nuclear layer (ONL). In mature zebrafish, polySia
      immunoreactivity in the ONL extended to the entire retina. Colocalization with
      rhodopsin-EGFP in transgenic zebrafish or the Muller glia-specific protein
      cellular retinaldehyde-binding protein (CRALBP) revealed that polySia
      immunoreactivity was confined to the compartment of radial Muller glia processes
      crossing the ONL and to a small band of processes positioned proximal to the
      horizontal cell layer of the mature retina. As shown by 5-bromo-2-deoxyuridine
      (BrdU) labeling, both newly generated rod precursors within the mature ONL and
      precursors of the marginal zone were polySia-negative. Thus, polySia-negative rod
      precursors of the mature zebrafish retina face a polySia-NCAM-positive
      microenvironment presented by radial Muller glia. In view of the prominent role
      of polySia in other neurogenic systems, this pattern indicates that polySia
      provides environmental cues that are relevant for the generation of new rods.

PMID- 20034056
TI  - Vesicular glutamate transporter 3-expressing nonserotonergic projection neurons
      constitute a subregion in the rat midbrain raphe nuclei.
AB  - We previously reported that about 80% of vesicular glutamate transporter 3
      (VGLUT3)-positive cells displayed immunoreactivity for serotonin, but the others
      were negative in the rat midbrain raphe nuclei, such as the dorsal (DR) and
      median raphe nuclei (MnR). In the present study, to investigate the precise
      distribution of VGLUT3-expressing nonserotonergic neurons in the DR and MnR, we
      performed double fluorescence in situ hybridization for VGLUT3 and tryptophan
      hydroxylase 2 (TPH2). According to the distribution of VGLUT3 and TPH2 mRNA
      signals, we divided the DR into six subregions. In the MnR and the rostral (DRr),
      ventral (DRV), and caudal (DRc) parts of the DR, VGLUT3 and TPH2 mRNA signals
      were frequently colocalized (about 80%). In the lateral wings (DRL) and core
      region of the dorsal part of the DR (DRDC), TPH2-producing neurons were
      predominantly distributed, and about 94% of TPH2-producing neurons were negative
      for VGLUT3 mRNA. Notably, in the shell region of the dorsal part of the DR
      (DRDSh), VGLUT3 mRNA signals were abundantly detected, and about 75% of VGLUT3
      expressing neurons were negative for TPH2 mRNA. We then examined the projection
      of VGLUT3-expressing nonserotonergic neurons in the DRDSh by anterograde and
      retrograde labeling after chemical depletion of serotonergic neurons. The
      projection was observed in various brain regions such as the ventral tegmental
      area, substantia nigra pars compacta, hypothalamic nuclei, and preoptic area.
      These results suggest that VGLUT3-expressing nonserotonergic neurons in the
      midbrain raphe nuclei are preferentially distributed in the DRDSh and modulate
      many brain regions with the neurotransmitter glutamate via ascending axons.

PMID- 20034057
TI  - Expression of transient receptor potential ankyrin 1 (TRPA1) in the rat
      trigeminal sensory afferents and spinal dorsal horn.
AB  - Transient receptor potential ankyrin 1 (TRPA1), responding to noxious cold and
      pungent compounds, is implicated in the mediation of nociception, but little is
      known about the processing of the TRPA1-mediated nociceptive information within
      the trigeminal sensory nuclei (TSN) and the spinal dorsal horn (DH). To address
      this issue, we characterized the TRPA1-positive (+) neurons in the trigeminal
      ganglion (TG) and investigated the distribution of TRPA1(+) afferent fibers and
      their synaptic connectivity within the rat TSN and DH by using light and electron
      microscopic immunohistochemistry. In the TG, TRPA1 was expressed in unmyelinated
      and small myelinated axons and also occasionally in large myelinated axons. Many
      TRPA1(+) neurons costained for the marker for peptidergic neurons substance P
      (26.8%) or the marker for nonpeptidergic neurons IB4 (44.5%). In the CNS, small
      numbers of axons and terminals were immunopositive for TRPA1 throughout the
      rostral TSN, in contrast to the dense network of positive fibers and terminals in
      the superficial laminae of the trigeminal caudal nucleus (Vc) and DH. The
      TRPA1(+) terminals contained clear round vesicles, were presynaptic to one or two
      dendrites, and rarely participated in axoaxonic contacts, suggesting involvement
      in relatively simple synaptic circuitry with a small degree of synaptic
      divergence and little presynaptic modulation. Immunoreactivity for TRPA1 was also
      occasionally observed in postsynaptic dendrites. These results suggest that TRPA1
      dependent orofacial and spinal nociceptive input is processed mainly in the
      superficial laminae of the Vc and DH in a specific manner and may be processed
      differently between the rostral TSN and Vc.

PMID- 20034058
TI  - Peripheral facial nerve axotomy in mice causes sprouting of motor axons into
      perineuronal central white matter: time course and molecular characterization.
AB  - Generation of new axonal sprouts plays an important role in neural repair. In the
      current study, we examined the appearance, composition and effects of gene
      deletions on intrabrainstem sprouts following peripheral facial nerve axotomy.
      Axotomy was followed by the appearance of galanin(+) and calcitonin gene-related
      peptide (CGRP)(+) sprouts peaking at day 14, matching both large, neuropeptide(+)
      subpopulations of axotomized facial motoneurons, but with CGRP(+) sprouts
      considerably rarer. Strong immunoreactivity for vesicular acetylcholine
      transporter (VAChT) and retrogradely transported MiniRuby following its
      application on freshly cut proximal facial nerve stump confirmed their axotomized
      motoneuron origin; the sprouts expressed CD44 and alpha7beta1 integrin adhesion
      molecules and grew apparently unhindered along neighboring central white matter
      tracts. Quantification of the galanin(+) sprouts revealed a stronger response
      following cut compared with crush (day 7-14) as well as enhanced sprouting after
      recut (day 8 + 6 vs. 14; 14 + 8 vs. 22), arguing against delayed appearance of
      sprouting being the result of the initial phase of reinnervation. Sprouting was
      strongly diminished in brain Jun-deficient mice but enhanced in alpha7 null
      animals that showed apparently compensatory up-regulation in beta1, suggesting
      important regulatory roles for transcription factors and the sprout-associated
      adhesion molecules. Analysis of inflammatory stimuli revealed a 50% reduction 12
      48 hours following systemic endotoxin associated with neural inflammation and a
      tendency toward more sprouts in TNFR1/2 null mutants (P = 10%) with a reduced
      inflammatory response, indicating detrimental effects of excessive inflammation.
      Moreover, the study points to the usefulness of the facial axotomy model in
      exploring physiological and molecular stimuli regulating central sprouting.

PMID- 20034059
TI  - Regional and subcellular distribution of HDAC4 in mouse brain.
AB  - Histone deacetylases (HDACs) are part of a system that links epigenetic control
      of gene expression to a variety of environmental stimuli. Some HDACs, including
      HDAC4, shuttle between the cytoplasm and nucleus in response to physiological
      cues such as calcium signaling. HDAC4 mRNA is enriched in the brain, but the
      regional and subcellular protein expression pattern of HDAC4 is not known. Here
      we show that HDAC4 is more highly expressed in some brain regions than in others.
      HDAC4 is present in the perikaryial cytoplasm of most neurons but its nuclear
      localization is variable. In some areas, such as the dentate gyrus, nuclear
      expression is not detectable, whereas in other areas some neuronal nuclei contain
      HDAC4 immunoreactivity whereas others do not. In the cytoplasm, HDAC4
      immunoreactivity is punctate. Some of these puncta are present in dendritic
      spines where the strongest immunoreactivity is associated with the postsynaptic
      density. These data demonstrate that the regional and subcellular distribution of
      HDAC4 is heterogeneous and raise the possibilities that HDAC4 acts on nonhistone
      substrates in dendritic spines or that it shuttles between spine and nucleus to
      coordinate synaptic activity with gene expression.

PMID- 20034060
TI  - Altered balance of gamma-aminobutyric acidergic and glutamatergic afferent inputs
      in rostral ventrolateral medulla-projecting neurons in the paraventricular
      nucleus of the hypothalamus of renovascular hypertensive rats.
AB  - An imbalance of excitatory and inhibitory functions has been shown to contribute
      to numerous pathological disorders. Accumulating evidence supports the idea that
      a change in hypothalamic gamma-aminobutyric acid (GABA)-ergic inhibitory and
      glutamatergic excitatory synaptic functions contributes to exacerbated
      neurohumoral drive in prevalent cardiovascular disorders, including hypertension.
      However, the precise underlying mechanisms and neuronal substrates are still not
      fully elucidated. In the present study, we combined quantitative
      immunohistochemistry with neuronal tract tracing to determine whether plastic
      remodeling of afferent GABAergic and glutamatergic inputs into identified RVLM
      projecting neurons of the hypothalamic paraventricular nucleus (PVN-RVLM)
      contributes to an imbalanced excitatory/inhibitory function in renovascular
      hypertensive rats (RVH). Our results indicate that both GABAergic and
      glutamatergic innervation densities increased in oxytocin-positive, PVN-RVLM (OT
      PVN-RVLM) neurons in RVH rats. Despite this concomitant increase, time-dependent
      and compartment-specific differences in the reorganization of these inputs
      resulted in an altered balance of excitatory/inhibitory inputs in somatic and
      dendritic compartments. A net predominance of excitatory over inhibitory inputs
      was found in OT-PVN-RVLM proximal dendrites. Our results indicate that, along
      with previously described changes in neurotransmitter release probability and
      postsynaptic receptor function, remodeling of GABAergic and glutamatergic
      afferent inputs contributes as an underlying mechanism to the altered
      excitatory/inhibitory balance in the PVN of hypertensive rats.

PMID- 20034061
TI  - Polymorphisms in KCNE1 or KCNE3 are not associated with Meniere disease in the
      Caucasian population.
AB  - Meniere disease (MD) is a complex disorder of unknown etiology characterized by
      the symptom triad of vertigo, sensorineural hearing loss, and tinnitus. Its
      reported incidence is 1-2 per 1,000 in Caucasians and 0.03-0.37 per 1,000 in
      Japanese. Doi et al. [Doi et al. (2005); ORL J Otorhinolaryngol Relat Spec 67:289
      293] recently reported that two single nucleotide polymorphisms (SNPs) in KCNE1
      and KCNE3 are associated with MD in Japanese subjects. Consistent with this
      possibility, these two genes encode potassium channels that are expressed in the
      stria vascularis and endolymphatic sac, respectively, and their role in ion
      transport suggests that they may be important in inner ear homeostasis. To
      establish whether a similar association exists in the Caucasian MD population, we
      sequenced the coding regions and exon-intron boundaries of both genes in 180
      Caucasian persons with MD and 180 matched Caucasian controls. Neither of the two
      reported SNPs was significantly associated with MD when compared to the Caucasian
      controls (KCNE1, P = 0.55; KCNE3, P = 0.870). Comparison of allele frequencies
      between the Japanese MD population and our study population revealed no
      significant difference between groups (KCNE1, P = 0.90; KCNE3, P = 0.862),
      suggesting that the significant differences reported in the Japanese study arose
      from their control population. Six additional SNPs in both KCNE1 and KCNE3 were
      genotyped and none was associated with MD. Population stratification within our
      MD and Caucasian control population was excluded. Our data show that SNPs in
      KCNE1 and KCNE3 are not associated with MD in Caucasians.

PMID- 20034064
TI  - Living with Costello syndrome: quality of life issues in older individuals.
AB  - Clinical and molecular analyses of Costello syndrome are proceeding at a rapid
      pace, including the delineation of the adult phenotype. We designed a two-part
      survey in order to describe the quality of life (QoL) of older individuals with
      Costello syndrome. The survey consisted of the Costello syndrome quality of life
      (CSQoL): Caregiver Questionnaire, to obtain objective information such as skills,
      activities, and medical issues from caregivers; and the CSQoL:Self-Questionnaire
      assessing subjective information including self-esteem, life satisfaction, and
      interpersonal relations from affected individuals. Thirteen of 18 (72%)
      individuals with Costello syndrome (age 16-34 years, mean 22 years) and caregiver
      pairs responded. The data were analyzed to study day-to-day life, and to
      determine potential impediments on QoL for older individuals with Costello
      syndrome. The CSQoL:Caregiver total scores were significantly lower than the
      CSQoL:Self total scores as demonstrated by the Wilcoxon Signed Ranks Test (P <
      0.008). The CSQoL:Caregiver total scores appear negatively correlated with total
      number of medical issues (r = -0.549; P = 0.065). No association was found
      between the CSQoL:Self scores and total number of medical issues (r = -0.107; P =
      0.769). Four impediments to QoL for individuals with Costello syndrome were
      identified: relationships outside of their immediate circle of family and
      friends, lack of independence, male gender, and the presence of major medical
      issues. This information may be useful to the families and health care
      professionals of adults with Costello syndrome. As a measurable characteristic,
      QoL may have utility as a metric in future therapeutic trials.

PMID- 20034065
TI  - A paternally transmitted complex chromosomal rearrangement (CCR) involving
      chromosomes 2, 6, and 18 includes eight breakpoints and five insertional
      translocations (ITs) through three generations.
AB  - Complex chromosomal rearrangements (CCRs) are uncommon and mainly occur de novo.
      We report here on a familial CCR involving chromosomes 2, 6, and 18. The
      propositus is a boy first referred because of growth delays, hypotonia, and
      facial anomalies, suggestive of deletion 18q syndrome. However, a cytogenetic
      family study disclosed a balanced CCR in three generations, which was detailed by
      FISH using BAC clones, and consisted of eight breakpoints with five insertional
      translocations (ITs). The propositus had a cryptic 18q deletion and a 6p
      duplication. Paternal transmission of this CCR was observed through three
      generations without meiotic recombination. Our investigation allowed us to
      provide porosities counseling and management of prenatal diagnosis for propositus
      cousin who carries this particular CCR.

PMID- 20034062
TI  - Selective long-term reorganization of the corticospinal projection from the
      supplementary motor cortex following recovery from lateral motor cortex injury.
AB  - Brain injury affecting the frontal motor cortex or its descending axons often
      causes contralateral upper extremity paresis. Although recovery is variable, the
      underlying mechanisms supporting favorable motor recovery remain unclear. Because
      the medial wall of the cerebral hemisphere is often spared following brain injury
      and recent functional neuroimaging studies in patients indicate a potential role
      for this brain region in the recovery process, we investigated the long-term
      effects of isolated lateral frontal motor cortical injury on the corticospinal
      projection (CSP) from intact, ipsilesional supplementary motor cortex (M2). After
      injury to the arm region of the primary motor (M1) and lateral premotor (LPMC)
      cortices, upper extremity recovery is accompanied by terminal axon plasticity in
      the contralateral CSP but not the ipsilateral CSP from M2. Furthermore,
      significant contralateral plasticity occurs only in lamina VII and dorsally
      within lamina IX. Thus, selective intraspinal sprouting transpires in regions
      containing interneurons, flexor-related motor neurons, and motor neurons
      supplying intrinsic hand muscles, which all play important roles in mediating
      reaching and digit movements. After recovery, subsequent injury of M2 leads to
      reemergence of hand motor deficits. Considering the importance of the CSP in
      humans and the common occurrence of lateral frontal cortex injury, these findings
      suggest that spared supplementary motor cortex may serve as an important
      therapeutic target that should be considered when designing acute and long-term
      postinjury patient intervention strategies aimed to enhance the motor recovery
      process following lateral cortical trauma.

PMID- 20034063
TI  - Initial loss but later excess of GABAergic synapses with dentate granule cells in
      a rat model of temporal lobe epilepsy.
AB  - Many patients with temporal lobe epilepsy display neuron loss in the dentate
      gyrus. One potential epileptogenic mechanism is loss of GABAergic interneurons
      and inhibitory synapses with granule cells. Stereological techniques were used to
      estimate numbers of gephyrin-positive punctae in the dentate gyrus, which were
      reduced short-term (5 days after pilocarpine-induced status epilepticus) but
      later rebounded beyond controls in epileptic rats. Stereological techniques were
      used to estimate numbers of synapses in electron micrographs of serial sections
      processed for postembedding GABA-immunoreactivity. Adjacent sections were used to
      estimate numbers of granule cells and glutamic acid decarboxylase-positive
      neurons per dentate gyrus. GABAergic neurons were reduced to 70% of control
      levels short-term, where they remained in epileptic rats. Integrating synapse and
      cell counts yielded average numbers of GABAergic synapses per granule cell, which
      decreased short-term and rebounded in epileptic animals beyond control levels.
      Axo-shaft and axo-spinous GABAergic synapse numbers in the outer molecular layer
      changed most. These findings suggest interneuron loss initially reduces numbers
      of GABAergic synapses with granule cells, but later, synaptogenesis by surviving
      interneurons overshoots control levels. In contrast, the average number of
      excitatory synapses per granule cell decreased short-term but recovered only
      toward control levels, although in epileptic rats excitatory synapses in the
      inner molecular layer were larger than in controls. These findings reveal a
      relative excess of GABAergic synapses and suggest that reports of reduced
      functional inhibitory synaptic input to granule cells in epilepsy might be
      attributable not to fewer but instead to abundant but dysfunctional GABAergic
      synapses.

PMID- 20034066
TI  - Chromosome 6 between-arm intrachromosomal insertion with intrasegmental double
      inversion: a four-break model.

PMID- 20034067
TI  - An unusual severe vascular case of pseudoxanthoma elasticum presenting as
      generalized arterial calcification of infancy.
AB  - Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease affecting
      tissues rich in elastic fibers such as the skin, retina, and cardiovascular
      system. Mutations in the ABCC6 gene are known to be causative in most patients.
      Generalized arterial calcification of infancy (GACI) is characterized by
      extensive hydroxyapatite deposits in the internal elastic laminae in large and
      medium-sized arteries, leading to arterial stenoses and early and severe
      myocardial ischemia. GACI has been found to be primarily caused by mutations in
      the ENPP1 gene. We report two brothers born to unrelated parents. The elder
      developed uncomplicated PXE in adolescence and harbored mutations in the ABCC6
      gene. The younger child died of a condition strikingly reminiscent of GACI at 15
      months of age. This case of GACI was independent of mutations in the ENPP1 gene
      but was probably related to ABCC6 mutations. We demonstrate that matrix Gla
      protein and fetuin-A, involved in PXE, are also expressed in this case of GACI.
      These proteins could act as local and systemic inhibitors to limit the extension
      of mineralization. This report emphasizes concurrently that ABCC6 may be a
      relevant candidate gene in some cases of GACI with no mutations in the ENPP1
      gene, and that GACI may be an atypical and severe end of the vascular phenotype
      spectrum of PXE.

PMID- 20034068
TI  - Homozygosity for the common mutation c.1085dupT in the ZMPSTE24 gene in a
      Mennonite baby with restrictive dermopathy and placenta abruption.

PMID- 20034071
TI  - Ectodermal dysplasia-like syndrome with mental retardation due to contiguous gene
      deletion: further clinical and molecular delineation of del(2q32) syndrome.
AB  - We report on a patient with an interstitial deletion of the long arm of
      chromosome 2 at 2q31.2q33.2. She had prenatal and postnatal growth retardation,
      microcephaly, facial dysmorphism, cleft palate, camptodactyly, bilateral talipes
      equinovarus, severe intellectual disability, and ectodermal anomalies. She showed
      thin, atrophic skin, sparse, brittle, slowly growing hair, oligodontia with
      abnormally shaped teeth, normal sweating, and normal fingernails, consistent with
      a diagnosis of ectodermal dysplasia. Array CGH analysis (Agilent 44K) showed the
      deletion to span 26 Mb, between cytogenetic bands 2q31.2 and 2q33. The deletion
      leads to hemizygosity for the HOXD cluster and its regulatory elements,
      COL3A1/COL5A2, GTF3C3, CASP8, CASP10, and SABT2 could perhaps interfere with long
      range control of DLX1 and DLX2 expression. This girl confirms the existence of a
      clinically recognizable 2q32 microdeletion syndrome, as recently delineated by
      Van Buggenhout et al. and confirms a novel putative locus for ectodermal
      dysplasia on chromosome 2q31q33. We recommend considering cytogenetic and/or
      molecular screening for del(2q32) in patients with developmental disability and
      ectodermal dysplasia-like phenotype, including thin skin, oligodontia, dysplastic
      teeth, and sparse hair.

PMID- 20034073
TI  - Expression and regulation of ANTXR1 in the chick embryo.
AB  - Anthrax Toxin Receptor 1 (ANTXR1; also known as Tumor Endothelial Marker 8, TEM8)
      is one of several genes that was recently found to be up-regulated in tumor
      associated endothelial cells. In vitro, the protein can link extracellular matrix
      components with the actin cytoskeleton to promote cell adhesion and cell
      spreading. Both, ANTXR1 and the closely related ANTXR2 can bind anthrax toxin and
      interact with lipoprotein receptor-related protein 5 and 6, which also work as
      coreceptors in the WNT signaling pathway. Here, we report the cloning of chick
      ANTXR1 from a suppression subtractive hybridization screen for fibroblast growth
      factor (FGF) -inducible genes in chicken embryonic facial mesenchyme. We show
      that chicken ANTXR1 is dynamically expressed throughout embryogenesis, starting
      from Hamburger and Hamilton stage 10. Furthermore, we demonstrate that FGF
      signaling is sufficient, but not necessary, to induce ANTXR1 expression in
      chicken facial mesenchyme.

PMID- 20034074
TI  - Review of the recently defined molecular mechanisms underlying thanatophoric
      dysplasia and their potential therapeutic implications for achondroplasia.
AB  - Achondroplasia (ACH), thanatophoric dysplasia (TD) types I and II,
      hypochondroplasia (HCH), and severe achondroplasia with developmental delay and
      acanthosis nigricans (SADDAN) are all due to activating mutations in the
      fibroblast growth factor receptor 3 (FGFR3) gene. We review the clinical,
      epidemiological, radiological, molecular aspects, and signaling pathways involved
      in these conditions. It is known that FGFR3 signaling is essential to regulate
      bone growth. The signal transducers and activators of transcription (STAT1)
      pathway is involved in the inhibition of chondrocyte proliferation, and the
      mitogen-activated protein kinase (MAPK) pathways are involved in chondrocyte
      differentiation. Hence, FGFR3 signaling is pivotal in chondrocyte differentiation
      and proliferation through these two different active pathways. Recent studies on
      the molecular mechanisms involved in chondrocyte differentiation and
      proliferation, demonstrated that Snail1 participates in the control of
      longitudinal bone growth and appears to be essential to transduce FGFR3 signaling
      during chondrogenesis. This result was confirmed in a newborn infant with TD, and
      suggests new non-surgical therapeutic approaches, that is, Snail1 as a new
      encouraging therapeutic target.

PMID- 20034076
TI  - GAPO syndrome associated with craniofacial vascular malformation.

PMID- 20034077
TI  - Variegated aneuploidy and ring chromosome syndromes overlap.

PMID- 20034078
TI  - Genetic counseling for schizophrenia: a review of referrals to a provincial
      medical genetics program from 1968 to 2007.
AB  - Recent studies have shown that individuals with schizophrenia and their family
      members are interested in genetic counseling, but few have received this service.
      We conducted an exploratory, retrospective study to describe (a) the population
      of individuals who were referred to the BC provincial medical genetics program
      for genetic counseling for a primary indication of schizophrenia, and (b) trends
      in number of referrals between 1968 and 2007. Referrals for a primary indication
      of schizophrenia were identified through the provincial program database. Charts
      were reviewed and the following information was recorded: discipline of referring
      physician, demographics, psychiatric diagnosis, referred individual's and
      partner's (if applicable) family history, and any current pregnancy history. Data
      were characterized using descriptive statistics. Our results showed that between
      1968 and 2007, 288 referrals were made for a primary indication of schizophrenia.
      Most referrals were made: (a) for individuals who had a first-degree family
      member with schizophrenia, rather than for affected individuals, (b) for
      preconception counseling, and (c) by family physicians (69%), with only 2% by
      psychiatrists. In conclusion, for British Columbia, individuals affected with
      schizophrenia and their family members are rarely referred for psychiatric
      genetic counseling. There is a need to identify barriers to psychiatric genetic
      counseling and develop strategies to improve access.

PMID- 20034079
TI  - An 18-year follow-up report on an infant with a duplication of 9q34.

PMID- 20034080
TI  - Draft recommendations suggest HHS exempt gene patents from infringement
      liability.

PMID- 20034082
TI  - An unusual phenotypic presentation of trisomy 18.

PMID- 20034083
TI  - Systematized organoid epidermal nevus with eccrine differentiation, multiple
      facial and oral congenital scars, gingival synechiae, and blepharophimosis: a
      novel epidermal nevus syndrome.
AB  - Epidermal nevus syndrome is a clinically variable and genetically heterogeneous
      group of mosaic conditions characterized by the concurrence of extensive
      epidermal nevus with additional cutaneous and extracutaneous manifestations. This
      term groups together well-characterized clinical entities, as well as dozens of
      apparently unique associations, which need further delineation. We report on a 23
      year-old woman presenting the previously undescribed combination of widespread
      eccrine proliferation, multiple facial and oral pox-like lesions, gingival
      synechiae, blepharophimosis, body asymmetry, and mental retardation. The patient
      has a healthy monozygotic twin. The eccrine proliferation is intermingled with
      areas of unaffected skin with a linear/segmental distribution on the limbs. The
      clinical presentation of such a complex phenotype fits well with the genetic
      mosaicism theory. The histologic findings, consisting of proliferation of
      immature to well-formed eccrine duct-like structures located in the deep dermis
      and interspersed with an abundant fibrous stroma constituted of horizontally
      oriented collagen fibers, seem a possible hallmark of this condition.

PMID- 20034085
TI  - A de novo 8.8-Mb deletion of 21q21.1-q21.3 in an autistic male with a complex
      rearrangement involving chromosomes 6, 10, and 21.
AB  - We report here on a normal-appearing male with pervasive developmental disorder
      who was found to have a de novo, apparently balanced complex rearrangement
      involving chromosomes 6, 10, and 21:
      46,XY,ins(21;10)(q11.2;p11.2p13)t(6;21)(p23;q11.2). Further analysis by high
      density oligonucleotide microarray was performed, showing an 8.8-Mb heterozygous
      deletion at 21q21.1-q21.3. Interestingly, the deletion is distal to the
      translocation breakpoint on chromosome 21. The deletion involves 19 genes,
      including NCAM2 and GRIK1, both of which are associated with normal brain
      development and function, and have been considered as possible candidate genes in
      autism and other neurobehavioral disorders. This case underscores the utility of
      genomewide microarray analysis for the detection of copy number alterations in
      patients with apparently balanced complex rearrangements and abnormal phenotypes.

PMID- 20034086
TI  - Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma
      syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling
      microarray.
AB  - Osteoporosis-pseudoglioma syndrome (OPS; OMIM 259770) is an autosomal-recessive
      genetic disorder characterized by severe osteoporosis and visual disturbance from
      childhood. Biallelic mutations in the low-density lipoprotein receptor-related
      protein 5 gene (LRP5) have been frequently detected, while a subset of patients
      had only one or no detectable mutation. We report on the clinical and molecular
      findings of four unrelated Japanese patients with the syndrome. The four patients
      had typical skeletal and ocular phenotypes of OPS, namely severe juvenile
      osteoporosis and early-onset visual disturbance, with or without mental
      retardation. We undertook standard PCR-based sequencing for LRP5 and found four
      missense mutations (p.L145F, p.T244M, p.P382L, and p.T552M), one nonsense
      mutation (p.R1534X), and one splice site mutation (c.1584+1G>A) among four OPS
      patients. Although three patients had two heterozygous mutations, one had only
      one heterozygous splice site mutation. In this patient, RT-PCR from lymphocytic
      RNA demonstrated splice error resulting in 63-bp insertion between exons 7 and 8.
      Furthermore, the patient was found to have only mutated RT-PCR fragment, implying
      that a seemingly normal allele did not express LRP5 mRNA. We then conducted
      custom- designed oligonucleotide tiling microarray analyses targeted to a 600-kb
      genome region harboring LRP5 and discovered a 7.2-kb microdeletion encompassing
      exons 22 and 23 of LRP5. We found various types of LRP5 mutations, including an
      exon-level deletion that is undetectable by standard PCR-based mutation
      screening. Oligonucleotide tiling microarray seems to be a powerful tool in
      identifying cryptic structural mutations.

PMID- 20034087
TI  - Speech characteristics in neurofibromatosis type 1.
AB  - Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder often accompanied
      with varying degrees of cognitive and motor problems that potentially affect
      speech and language. While previous studies have shown that NF1 may be associated
      with a variety of deviations in the patients' speech, they have not investigated
      the characteristics in phonetic detail. Our clinical observation that many
      patients share a distinct voice and manner of speaking led to the primary aim of
      this study, which was to present a comprehensive description of speech in NF1. A
      total of 62 patients with NF1 (age range 7-66 years), and a control group of 24
      speakers (age range 7-62 years) were evaluated for their speech. The test
      sessions were recorded and the data were analyzed both by ear and by acoustic
      measurements. The data were analyzed separately by two trained phoneticians, and
      a summary was produced after comparing the two independent analyses. Various
      speech problems were observed among patients with NF1. Individual variation was
      remarkable, but the deviations were more common and severe in children than in
      adult patients. In addition, men with NF1 had more speech deviations than women
      with NF1. Findings include deviations in voice quality, problems in regulating
      pitch, deviant nasality, misarticulation, and disfluency. We suggest that
      difficulties in speech, particularly in regulating pitch, may have negative
      social implications. Our results highlight which components of speech require
      particular attention in speech therapy for patients with NF1.

PMID- 20034088
TI  - A novel UBE3A truncating mutation in large Tunisian Angelman syndrome pedigree.
AB  - We identified in a large Tunisian pedigree a novel UBE3A frameshift mutation in
      exon 16 coding region, and we expect that the resulting UBE3A truncated protein
      in our patients is non-functional since the mutation implies the catalytic region
      of the enzyme. The family includes 14 affected patients born from four sisters.
      This mutation was found in all surviving affected individuals and their mothers
      pointing out the importance of genetic counseling possibility in Angelman
      syndrome (AS). All patients had severe mental retardation with epilepsy and
      microcephaly. Minor clinical expression variation was observed among the
      investigated patients. The severity of clinical expression is related to the
      detected molecular variation: deletion of 15 bp and insertion of 7 bp. These
      results are concordant with the gene expression observed in previously reported
      individuals with AS and truncated UBE3A protein.

PMID- 20034090
TI  - Ring chromosome 14 mosaicism: an unusual case associated with developmental delay
      and epilepsy, characterized by genome array-CGH.

PMID- 20034091
TI  - Further evidence for EpCAM as the gene for congenital tufting enteropathy.

PMID- 20034092
TI  - Phenotypic map in ring 14 syndrome.

PMID- 20034089
TI  - Sperm and oocyte communication mechanisms controlling C. elegans fertility.
AB  - During sexual reproduction in many species, sperm and oocyte secrete diffusible
      signaling molecules to help orchestrate the biological symphony of fertilization.
      In the Caenorhabditis elegans gonad, bidirectional signaling between sperm and
      oocyte is important for guiding sperm to the fertilization site and inducing
      oocyte maturation. The molecular mechanisms that regulate sperm guidance and
      oocyte maturation are being delineated. Unexpectedly, these mechanisms are
      providing insight into human diseases, such as amyotrophic lateral sclerosis,
      spinal muscular atrophy, and cancer. Here we review sperm and oocyte
      communication in C. elegans and discuss relationships to human disorders.

PMID- 20034093
TI  - Holoprosencephaly-diencephalic hamartoma: sequence or pleiotropy?

PMID- 20034094
TI  - Risk of breast cancer not increased in translocation 11;22 carriers: analysis of
      80 pedigrees.

PMID- 20034095
TI  - CHN1 mutations are not a common cause of sporadic Duane's retraction syndrome.

PMID- 20034096
TI  - Loss of N-acetylglucosamine-1-phosphotransferase gamma subunit due to intronic
      mutation in GNPTG causes mucolipidosis type III gamma: Implications for molecular
      and cellular diagnostics.
AB  - Mucolipidosis type III gamma (MLIII, pseudo-Hurler polydystrophy) is a rare
      autosomal recessive disorder where the activity of the multimeric GlcNAc-1
      phosphotransferase is reduced and formation of the mannose 6-phosphate (M6P)
      recognition marker on lysosomal enzymes is impaired. In this disease, the
      targeting of lysosomal enzymes is affected resulting in their hypersecretion, and
      an intracellular deficiency of multiple hydrolases. We report the biochemical and
      molecular diagnosis of MLIII in three siblings, aged 17, 15, and 14 years, who
      presented with joint pain and progressive joint stiffness. In addition to
      missorting of newly synthesized lysosomal protease cathepsin D, there were low
      levels of M6P-containing proteins in cell extracts and media of cultured
      fibroblasts of the Patients. Direct sequencing identified a novel homozygous
      mutation in intron 7, IVS7-10G>A, of the GNPTG gene, which encodes the gamma
      subunit of the GlcNAc-1-phosphotransferase. This mutation created a cryptic 3'
      splice site resulting in a frameshift and premature translational termination
      (p.V176GfsX18). The GNPTG mRNA levels were markedly reduced in Patients'
      fibroblasts indicating that the intronic mutation mediates mRNA decay, which was
      confirmed by absence of the gamma-subunit protein. These data contribute to an
      efficient diagnostic strategy to identify Patients with MLIII gamma and
      characterize their biochemical defect in fibroblasts.

PMID- 20034097
TI  - Left ventricular noncompaction: a rare disorder in adults and its association
      with 1p36 chromosomal anomaly.
AB  - We report on a case of a 25-year-old male with 1p36 deletion syndrome, who was
      diagnosed with left ventricular noncompaction (LVNC). The association of this
      rare chromosomal abnormality with LVNC is reported in the pediatric literature,
      but it has not previously been specifically reported in adults. It is important
      to diagnose this unclassified cardiomyopathy in the adult population with this
      chromosomal abnormality for appropriate management and treatment as highlighted
      in our case.

PMID- 20034099
TI  - Wolf-Hirschhorn syndrome and ectrodactyly: New findings and a review of the
      literature.

PMID- 20034098
TI  - Diagnostic utility of daytime salivary melatonin levels in Smith-Magenis
      syndrome.
AB  - An inverted circadian rhythm of melatonin (MT) likely contributes to the sleep
      disturbance in patients with Smith-Magenis syndrome (SMS). Plasma MT levels have
      documented this altered rhythm, but daytime levels of salivary MT has not been
      determined. Daytime measures of salivary MT might have utility in home/outpatient
      settings for assessing MT levels in undiagnosed patients with clinical features
      of SMS. The objective of this study was to determine the utility of daytime
      salivary MT as a diagnostic test in SMS. Thirty individuals with confirmed SMS
      [28 with del 17p11.2 and 2 with the retinoic acid induced 1 (RAI1) gene mutation]
      and five controls were studied. Single or serial daytime salivary MT levels were
      measured. The mean midday salivary MT level was 79.0 pg/ml in SMS patients,
      compared with 16.3 pg/ml in controls, with nine patients having values similar to
      controls. The median MT level in SMS patients was 49.0 pg/ml (first and third
      quartile values = 15.5 and 106.8 pg/ml). Twenty-six (90%) of 29 patients had at
      least one MT value >15.5 pg/ml, including 70 (78%) of 90 samples from patients
      with del 17p11.2 and one (20%) of five samples from the two patients with the
      RAI1 mutation. Neither the pattern of medication use nor age had an effect on
      daytime salivary MT levels. Although most SMS patients had elevated daytime
      salivary MT levels, multiple sampling appears necessary to distinguish patients
      with SMS from other conditions.

PMID- 20034100
TI  - Extending the phenotype of monosomy 1p36 syndrome and mapping of a critical
      region for obesity and hyperphagia.
AB  - Rearrangements of 1p36 are the most frequently detected abnormalities in
      diagnostic testing for chromosomal cryptic imbalances and include variably sized
      simple terminal deletions, derivative chromosomes, interstitial deletions, and
      complex rearrangements. These rearrangements result in the specific pattern of
      malformation and neurodevelopmental disabilities that characterizes monosomy 1p36
      syndrome. Thus far, no individual gene within this region has been conclusively
      determined to be causative of any component of the phenotype. Nor is it known if
      the rearrangements convey phenotypes via a haploinsufficiency mechanism or
      through a position effect. We have used multiplex ligation-dependent probe
      amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and
      overweight/obese, PWS negative individuals, and in a separate group of 83
      patients initially sent to investigate a variety of other conditions. The
      strategy allowed the identification and delineation of rearrangements in nine
      subjects with a wide spectrum of clinical presentations. Our work reinforces the
      association of monosomy 1p36 and obesity and hyperphagia, and further suggests
      that these features may be associated with non-classical manifestations of this
      disorder in addition to a submicroscopic deletion of approximately 2-3 Mb in
      size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome
      specific kit coupled to the subtelomeric kit is an effective approach to identify
      and delineate rearrangements at 1p36.

PMID- 20034101
TI  - Integration of human model neurons (NT2) into embryonic chick nervous system.
AB  - Postmitotic neurons were generated from the human NT2 teratocarcinoma cell line
      in a novel cell aggregate differentiation procedure. Approximately a third of the
      differentiated neurons expressed cell markers related to cholinergic
      neurotransmission. To examine whether this human cell model system can be
      directed toward a motoneuronal fate, postmitotic neurons were co-cultured with
      mouse myotubes. Outgrowing neuronal processes established close contact with the
      myotubes and formed neuromuscular junction-like structures that bound alpha
      bungarotoxin. To determine how grafted precursor cells and neurons respond to
      embryonic nerve tissue, NT2 cells at different stages of neural development were
      injected into chick embryo neural tube and brain. Grafted NT2 neurons populated
      both parts of the nervous system, sometimes migrating away from the site of
      injection. The neural tube appeared to be more permissive for neurite extensions
      than the brain. Moreover, extending neurites of spinal grafts were approaching
      the ventral roots, thus resembling motoneuronal projections.

PMID- 20034102
TI  - Characterization of the neuroligin gene family expression and evolution in
      zebrafish.
AB  - Neuroligins constitute a family of transmembrane proteins localized at the
      postsynaptic side of both excitatory and inhibitory synapses of the central
      nervous system. They are involved in synaptic function and maturation and recent
      studies have linked mutations in specific human Neuroligins to mental retardation
      and autism. We isolated the human Neuroligin homologs in Danio rerio. Next, we
      studied their gene structures and we reconstructed the evolution of the
      Neuroligin genes across vertebrate phyla. Using reverse-transcriptase polymerase
      chain reaction, we analyzed the expression and alternative splicing pattern of
      each gene during zebrafish embryonic development and in different adult organs.
      By in situ hybridization, we analyzed the temporal and spatial expression pattern
      during embryonic development and larval stages and we found that zebrafish
      Neuroligins are expressed throughout the nervous system. Globally, our results
      indicate that, during evolution, specific subfunctionalization events occurred
      within paralogous members of this gene family in zebrafish.

PMID- 20034103
TI  - Churchill and Sip1a repress fibroblast growth factor signaling during zebrafish
      somitogenesis.
AB  - Cell-type specific regulation of a small number of growth factor signal
      transduction pathways generates diverse developmental outcomes. The zinc finger
      protein Churchill (ChCh) is a key effector of fibroblast growth factor (FGF)
      signaling during gastrulation. ChCh is largely thought to act by inducing
      expression of the multifunctional Sip1 (Smad Interacting Protein 1). We
      investigated the function of ChCh and Sip1a during zebrafish somitogenesis.
      Knockdown of ChCh or Sip1a results in misshapen somites that are short and
      narrow. As in wild-type embryos, cycling gene expression occurs in the developing
      somites in ChCh and Sip1a compromised embryos, but expression of her1 and her7 is
      maintained in formed somites. In addition, tail bud fgf8 expression is expanded
      anteriorly in these embryos. Finally, we found that blocking FGF8 restores somite
      morphology in ChCh and Sip1a compromised embryos. These results demonstrate a
      novel role for ChCh and Sip1a in repression of FGF activity.

PMID- 20034104
TI  - Regulation of Sox9 by Sonic Hedgehog (Shh) is essential for patterning and
      formation of tracheal cartilage.
AB  - We report that Sonic Hedgehog (Shh) regulates both formation and patterning of
      tracheal cartilage by controlling the expression pattern and level of the
      chondrogenic gene, Sox9. In Shh(-/-) tracheo-esophageal tubes, Sox9 expression is
      transient and not restricted ventrally to the site of chondrogenesis, and is
      absent at the time of chondrogenesis, resulting in the failure of tracheal
      cartilage formation. Inhibition of Hedgehog signalling with cyclopamine in
      tracheal cultures prevents tracheal cartilage formation, while treatment of Shh(
      /-) tracheal explant with exogenous Shh peptide rescues cartilage formation. Both
      exogenous Bmp4 and Noggin rescue cartilage phenotype in Shh(-/-) tracheal
      culture, while promoting excessive cartilage development in wild-type trachea
      through induction of Sox9 expression. The ventral and segmented expression of
      Sox9 in tracheal primordia under Shh modulated by Bmp4 and Noggin thus determine
      where and when tracheal cartilage develops. These results indicate that Shh
      signalling is a critical determinant in tracheal cartilage development.

PMID- 20034105
TI  - Transcriptional regulatory regions of gap43 needed in developing and regenerating
      retinal ganglion cells.
AB  - Mammals and fish differ in their ability to express axon growth-associated genes
      in response to CNS injury, which contributes to the differences in their ability
      for CNS regeneration. Previously we demonstrated that for the axon growth
      associated gene, gap43, regions of the rat promoter that are sufficient to
      promote reporter gene expression in the developing zebrafish nervous system are
      not sufficient to promote expression in regenerating retinal ganglion cells in
      zebrafish. Recently, we identified a 3.6-kb gap43 promoter fragment from the
      pufferfish, Takifugu rubripes (fugu), that can promote reporter gene expression
      during both development and regeneration. Using promoter deletion analysis, we
      have found regions of the 3.6-kb fugu gap43 promoter that are necessary for
      expression in regenerating, but not developing, retinal ganglion cells. Within
      the 3.6-kb promoter, we have identified elements that are highly conserved among
      fish, as well as elements conserved among fish, mammals, and birds.

PMID- 20034106
TI  - Retinoic acid controls expression of tissue remodeling genes Hmgn1 and Fgf18 at
      the digit-interdigit junction.
AB  - Previous studies on retinoic acid receptor (RAR) mutants suggested that retinoic
      acid (RA) is required for loss of interdigital mesenchyme during digit formation.
      Here, we report that the RA-generating enzyme retinaldehyde dehydrogenase-2
      (Raldh2) is expressed in the interdigital mesenchyme whereas Cyp26b1, controlling
      RA degradation, is expressed in digits, limiting autopodal RA action to the
      interdigital zones. Embryonic day 13.5 Raldh2-/- mouse embryos lose expression of
      the RARE-lacZ RA-reporter transgene and matrix metalloproteinase-11 (Mmp11)
      throughout the interdigital mesenchyme, while expression of RARb, Fgf18, and high
      mobility group N1 (Hmgn1) is lost at the digit-interdigit junction. Raldh2-/-
      autopods exhibit reduced interdigital apoptosis associated with loss of Bmp7
      expression, but Bmp2, Bmp4, Msx2, and Fgf8 were unaffected. Although interdigital
      expression of Hmgn1 was greatly down-regulated in Raldh2-/- autopods,
      complementary expression of Sox9 in digit cartilage was unaffected. Regulation of
      Hmgn1 and Fgf18 at the digit-interdigit junction suggests RA controls tissue
      remodeling as well as apoptosis.

PMID- 20034108
TI  - NMR characterization of an engineered domain fusion between maltose binding
      protein and TEM1 beta-lactamase provides insight into its structure and
      allosteric mechanism.
AB  - RG13 is a 72 kDa engineered allosteric enzyme comprised of a fusion between
      maltose binding protein (MBP) and TEM1 beta-lactamase (BLA) for which maltose is
      a positive effector of BLA activity. We have used NMR spectroscopy to acquire
      [(15)N, (1)H]-TROSY-HSQC spectra of RG13 in the presence and absence of maltose.
      The RG13 chemical shift data was compared to the published chemical shift data of
      MBP and BLA. The spectra are consistent with the expectation that the individual
      domain structures of RG13 are substantially conserved from MBP and BLA.
      Differences in the spectra are consistent with the fusion geometry of MBP and BLA
      and the maltose-dependent differences in the kinetics of RG13 enzyme activity. In
      particular, the spectra provide evidence for a maltose-dependent conformational
      change of a key active site glutamate involved in deacylation of the enzyme
      substrate intermediate.

PMID- 20034107
TI  - Survival of Hoxa13 homozygous mutants reveals a novel role in digit patterning
      and appendicular skeletal development.
AB  - The loss of HOXA13 function severely disrupts embryonic limb development.
      However, because embryos lacking HOXA13 die by mid-gestation, the defects present
      in the mutant limb could arise as a secondary consequence of failing embryonic
      health. In our analysis of the mutant Hoxa13(GFP) allele, we identified a
      surviving cohort of homozygous mutants exhibiting severe limb defects including:
      missing phalanx elements, fusions of the carpal/tarsal elements, and significant
      reductions in metacarpal/metatarsal length. Characterization of prochondrogenic
      genes in the affected carpal/tarsal regions revealed significant reduction in
      Gdf5 expression, whereas Bmp2 expression was significantly elevated. Analysis of
      Gdf5 mRNA localization also revealed diffuse expression in the carpal/tarsal
      anlagen, suggesting a role for HOXA13 in the organization of the cells necessary
      to delineate individual carpal/tarsal elements. Together these results identify
      Gdf5 as a potential target gene of HOXA13 target gene and confirm a specific role
      for HOXA13 during appendicular skeletal development.

PMID- 20034110
TI  - FREAD revisited: Accurate loop structure prediction using a database search
      algorithm.
AB  - Loops are the most variable regions of protein structure and are, in general, the
      least accurately predicted. Their prediction has been approached in two ways, ab
      initio and database search. In recent years, it has been thought that ab initio
      methods are more powerful. In light of the continued rapid expansion in the
      number of known protein structures, we have re-evaluated FREAD, a database search
      method and demonstrate that the power of database search methods may have been
      underestimated. We found that sequence similarity as quantified by environment
      specific substitution scores can be used to significantly improve prediction. In
      fact, FREAD performs appreciably better for an identifiable subset of loops (two
      thirds of shorter loops and half of the longer loops tested) than the ab initio
      methods of MODELLER, PLOP, and RAPPER. Within this subset, FREAD's predictive
      ability is length independent, in general, producing results within 2A RMSD,
      compared to an average of over 10A for loop length 20 for any of the other tested
      methods. We also benchmarked the prediction protocols on a set of 212 loops from
      the model structures in CASP 7 and 8. An extended version of FREAD is able to
      make predictions for 127 of these, it gives the best prediction of the methods
      tested in 61 of these cases. In examining FREAD's ability to predict in the model
      environment, we found that whole structure quality did not affect the quality of
      loop predictions.

PMID- 20034109
TI  - Information-theoretic analysis of the reference state in contact potentials used
      for protein structure prediction.
AB  - Using information-theoretic concepts, we examine the role of the reference state,
      a crucial component of empirical potential functions, in protein fold
      recognition. We derive an information-based connection between the probability
      distribution functions of the reference state and those that characterize the
      decoy set used in threading. In examining commonly used contact reference states,
      we find that the quasi-chemical approximation is informatically superior to other
      variant models designed to include characteristics of real protein chains, such
      as finite length and variable amino acid composition from protein to protein. We
      observe that in these variant models, the total divergence, the operative
      function that quantifies discrimination, decreases along with threading
      performance. We find that any amount of nativeness encoded in the reference state
      model does not significantly improve threading performance. A promising avenue
      for the development of better potentials is suggested by our information
      theoretic analysis of the action of contact potentials on individual protein
      sequences. Our results show that contact potentials perform better when the
      compositional properties of the data set used to derive the score function
      probabilities are similar to the properties of the sequence of interest. Results
      also suggest to use only sequences of similar composition in deriving contact
      potentials, to tailor the contact potential specifically for a test sequence.

PMID- 20034111
TI  - Crystal structure of the MukB hinge domain with coiled-coil stretches and its
      functional implications.
AB  - The structural maintenance of chromosomes (SMC) family proteins are commonly
      found in the multiprotein complexes involved in chromosome organization,
      including chromosome condensation and sister chromatid cohesion. These proteins
      are characterized by forming a V-shaped homo- or heterodimeric structure with two
      long coiled-coil arms having two ATPase head domains at the distal ends. The
      hinge domain, located in the middle of the coiled coil, forms the dimer
      interface. In addition to being the dimerization module, SMC hinges appear to
      play other roles, including the gateway function for DNA entry into the cohesin
      complex. Herein, we report the homodimeric structure of the hinge domain of
      Escherichia coli MukB, which forms a prokaryotic condensin complex with two non
      SMC subunits, MukE and MukF. In contrast with SMC hinge of Thermotoga maritima
      which has a sizable central hole at the dimer interface, MukB hinge forms a
      constricted dimer interface lacking a hole. Under our assay conditions, MukB
      hinge does not interact with DNA in accordance with the absence of a notable
      positively charged surface patch. The function of MukB hinge appears to be
      limited to dimerization of two copies of MukB molecules.

PMID- 20034112
TI  - UV and X-ray structural studies of a 101-residue long Tat protein from a HIV-1
      primary isolate and of its mutated, detoxified, vaccine candidate.
AB  - The 101-residue long Tat protein of primary isolate 133 of the human
      immunodeficiency virus type 1 (HIV-1), wt-Tat(133) displays a high
      transactivation activity in vitro, whereas the mutant thereof, STLA-Tat(133), a
      vaccine candidate for HIV-1, has none. These two proteins were chemically
      synthesized and their biological activity was validated. Their structural
      properties were characterized using circular dichroism (CD), fluorescence
      emission, gel filtration, dynamic light scattering, and small angle X-ray
      scattering (SAXS) techniques. SAXS studies revealed that both proteins were
      extended and belong to the family of intrinsically unstructured proteins. CD
      measurements showed that wt-Tat(133) or STLA-Tat(133) underwent limited
      structural rearrangements when complexed with specific fragments of antibodies.
      Crystallization trials have been performed on the two forms, assuming that the
      Tat(133) proteins might have a better propensity to fold in supersaturated
      conditions, and small crystals have been obtained. These results suggest that
      biologically active Tat protein is natively unfolded and requires only a limited
      gain of structure for its function.

PMID- 20034117
TI  - Editorial: crystal-clear view of chemistry.

PMID- 20034113
TI  - Mapping of ligand-binding cavities in proteins.
AB  - The complex interactions between proteins and small organic molecules (ligands)
      are intensively studied because they play key roles in biological processes and
      drug activities. Here, we present a novel approach to characterize and map the
      ligand-binding cavities of proteins without direct geometric comparison of
      structures, based on Principal Component Analysis of cavity properties (related
      mainly to size, polarity, and charge). This approach can provide valuable
      information on the similarities and dissimilarities, of binding cavities due to
      mutations, between-species differences and flexibility upon ligand-binding. The
      presented results show that information on ligand-binding cavity variations can
      complement information on protein similarity obtained from sequence comparisons.
      The predictive aspect of the method is exemplified by successful predictions of
      serine proteases that were not included in the model construction. The presented
      strategy to compare ligand-binding cavities of related and unrelated proteins has
      many potential applications within protein and medicinal chemistry, for example
      in the characterization and mapping of "orphan structures", selection of protein
      structures for docking studies in structure-based design, and identification of
      proteins for selectivity screens in drug design programs.

PMID- 20034125
TI  - Cellular evaluation of synthesized insulin/transferrin bioconjugates for oral
      insulin delivery using intelligent complexation hydrogels.
AB  - Insulin transport across the epithelial cell layer in the small intestine was
      studied using insulin/transferrin conjugates with and without the presence of
      P(MAA-g-EG) microparticles in contact with a co-culture of Caco-2/HT29-MTX cells.
      The insulin/transferrin conjugate was shown to increase transport relative to
      pure insulin by a factor of 7, achieving an apparent permeability of 37 x 10(9)
      cm . s(-1). The presence of P(MAA-g-EG) microparticles increased conjugate
      transport by a factor of 14 times relative to insulin, achieving an apparent
      permeability of 72.8 x 10(9) cm . s(-1). The presence of the microparticles in
      solution was found to improve conjugate transport by nearly 100% with little to
      no change in cell monolayer integrity.

PMID- 20034127
TI  - Kaposi sarcoma is the most common cancer diagnosed in HIV-infected persons.

PMID- 20034128
TI  - Human papilloma virus infections and disease in HIV.

PMID- 20034129
TI  - Does ARV therapy reduce incidence of non-Hodgkin lymphoma?

PMID- 20034130
TI  - Nursing support is critical for patients with both cancer and HIV.

PMID- 20034132
TI  - Certain non-AIDS-defining cancers higher in HIV population.

PMID- 20034131
TI  - Hepatocellular carcinoma and HIV: is there an association?

PMID- 20034133
TI  - Interactions between antineoplastic agents and ARV drugs.

PMID- 20034134
TI  - New HIV primary care guidelines broaden focus, stress adherence. 'A big push to
      get patients to remain in care.'.

PMID- 20034135
TI  - Paperless: showing EHR benefits in HIV care.  Quality assurance easier, more
      efficient.

PMID- 20034136
TI  - HPV infection screening is important for HIV MSM. HIV & HPV connection studied.

PMID- 20034137
TI  - Use of HIV suspectibility testing linked to survival.  Clear support for GPT.

PMID- 20034138
TI  - Encourage condoms, with passion, please.

PMID- 20034139
TI  - FDA notifications.  New pediatric guidelines by NIH, CDC.

PMID- 20034140
TI  - FDA notifications.  Dear Healthcare letter for etravirine.

PMID- 20034141
TI  - FDA notifications. Generic efavirenz/emtricitabine/fenofovir has tentative
      approval.

PMID- 20034142
TI  - With H1N1 vaccine shortage expected, highest-risk groups go to front of line. 
      Who is at risk for serious infections and why?

PMID- 20034143
TI  - Rotavirus vaccines:an update.

PMID- 20034144
TI  - The 1932-1933 crisis and its aftermath beyond the epicenters of famine: the Urals
      region.

PMID- 20034145
TI  - Victory over the peasantry.

PMID- 20034146
TI  - The collectivization famine in Kazakhstan, 1931-1933.

PMID- 20034147
TI  - The great famine of 1932-1933: consequences and implications.

PMID- 20034148
TI  - [Sociological reflections on population statistics since the 17th century].

PMID- 20034149
TI  - ["These victims of racial persecution believe they can do whatever they want":
      denunciations between refugees and the established population in the Stade
      region, 1945-49].

PMID- 20034150
TI  - [The computerized register of population, an interdisciplinary tool applied to
      social science: the example of Vallouise-en-Brianconnais, 14th-20th centuries].

PMID- 20034151
TI  - Does Osgood-Schlatter disease exist in the dog? A comment.

PMID- 20034152
TI  - [Landmarks for a history of "ordinary clothing": the example of Meaux, 1590
      1670].

PMID- 20034154
TI  - Phonetics and speaking machines: on the mechanical simulation of human speech in
      the 17th century.

PMID- 20034153
TI  - [The evolution of the status of women in France: from submission to liberation,
      1880-1930?].

PMID- 20034155
TI  - Wilkomirski the victim: individual remembering as social interaction and public
      event.

PMID- 20034156
TI  - [International social and economic transformation since 1945].

PMID- 20034157
TI  - The introduction of the potato into Ireland.

PMID- 20034158
TI  - The Spanish Basque Irish fishery and trade in the sixteenth century.

PMID- 20034159
TI  - Lifelong resiliency learning:  A strength-based synergy for gerontological social
      work.

PMID- 20034160
TI  - Circadian periodicity, adrenal corticosteroids, and the EEG of normal man.
AB  - Human EEG activity in the conventional frequency range of 1-30 c/s is a well
      established entity. This paper illustrates a method for utilizing a conventional
      EEG frequency analyser to demonstrate a considerably lower frequency, circadian
      (about 24-h) rhythm in the EEGs of a group of human volunteers. This periodicity
      persists even in a group of totally sleep deprived (50 h) subjects. Plasma
      cortisol levels from blood samples drawn simultaneously with the EEG data also
      demonstrate circadian periodicity, and EEG-cortisol temporal (phase)
      relationships are apparent by inspection of the data collected, but could not be
      confirmed statistically. Evidence for the statistical significance of circadian
      organization of the EEGs and adrenal cortices of healthy men is provided by a
      phase testing technique developed for this study and discussed further in the
      appendix. This technique is readily applicable to further studies of periodicity
      in physiological functions.

PMID- 20034161
TI  - The differential effects of plasma from two groups of clinically similar
      schizophrenic patients on learning behavior in rats.
AB  - The effects of plasma from normal subjects and chronic schizophrenic patients
      were determined on the rate of learning a pole jump response in rats. The animals
      were trained to a buzzer CS and electroshock US. Mean trials to a 90 per cent
      avoidance criterion were determined using a 100 trial cut off. Plasma and other
      control solutions were given intraperitoneally in the morning and the procedure
      repeated in the afternoon with separate groups of rats. Test trials were
      initiated five minutes after injection. It was found that all plasma, in contrast
      to saline, produced an increase in the number of trials to learn the avoidance
      response. No difference in behavioral effects was noted comparing the plasma of
      all chronic schizophrenics to normals. However, within the chronic schizophrenic
      population there are subgroups whose plasma was differentially effective in
      reducing rate of learning. These results are preliminary and subject to continued
      experimentation. They are presented here to make others aware of the needto
      consider the existence of possible biologic subgroupings of schizophrenia in
      future investigations of the plasma-behavior interaction.

PMID- 20034162
TI  - Effectiveness and processes of interviewing with drugs.
AB  - A triple-blind study was made on forty-nine patients in regard to differences
      between sodium amobarbital, hydroxydione, methamphetamine and saline when used in
      psychiatric interviews. The drugs were found to differ from each other and from
      the placebo in their effects upon patients' speech, direction of attention and on
      anxiety. Other factors studied were not differentially affected by the drugs and
      placebo. Observers were able to identify correctly the drugs from observations,
      but two of the drugs, hydroxydione and sodium amobarbital, were often
      indistinguishable. Significant differences between judges' abilities to identify
      the drugs were also observed. Reports of the patients 24 h after the interviews
      reflected several significant differences between the drugs and placebo in
      changes in subjective feelings and attitudes. Such changes were reported more
      often with methamphetamine and sodium amobarbital than with hydroxydione or
      placebo. Implications of the study were discussed and suggestions for further
      research given.

PMID- 20034163
TI  - Time estimation, knowledge of results and drug effects.
AB  - 1. Knowledge of results can obscure the effects of a drug on time estimation,
      particularly when 10 s is estimated. The effect of such knowledge on 1 s
      estimation differs from the effect on 10 s estimation. 2. Secobarbital was the
      only drug which produced significant directional effects when tested with a
      nonparametric technique of moderate power. The effects of alcohol were found to
      be variable. The performance under d-amphetamine could not be discriminated from
      the performance under placebo. 3. Under the conditions of the present experiment,
      the one second estimation schedule appears more sensitive to drug effects than
      the 10 s schedule. 4. Timing responses were found to be sequentially dependent:
      within limits, successive interresponse times are positively correlated, a
      finding which warrants further study and elucidation.

PMID- 20034164
TI  - Effects of sensory deprivation on introverts and extraverts: a failure to find
      reported differences.
AB  - This study was stimulated by an earlier study by another investigator in which it
      was found that extraverts and introverts differed in their tendencies to quit the
      SD experiment prematurely, in amounts of movement during SD, and in their thought
      processes during SD. The present study compared 10 extraverts and 10 introverts
      in their reactions to SD. Ss were placed in a sound-deadened room with halved
      ping-pong balls covering their eyes and cardboard cuffs enclosing their lower
      arms and hands. The room was well-lighted and white noise was conveyed to Ss via
      headphones; however, Ss' eye coverings diffused the light and the loudness of the
      white noise blocked out ambient sounds so that Ss received only unpatterned
      visual and auditory stimulation. Ss were in SD for 3 h unless they requested
      early release. The two groups of Ss were compared on the following data: (a)
      Numbers of each group who quit the experiment prematurely; (b) Verbal reports
      given during SD; (c) Observations and recordings of visible movements during SD;
      (d) Self-ratings of well-being on a semantic differential type rating scale
      before and after SD; (e) Scores on the Minnesota Multiphasic Personality
      Inventory. The results disclosed no statistically significant differences between
      extraverts and introverts on any of the measures employed. These results were at
      variance with results obtained in the earlier study despite much similarity in S
      selection and method employed in both studies. The divergency of results suggests
      that whatever relation may exist between the extraversion-introversion dimension
      and reactions to SD may take more than 3 h to manifest itself or may interact
      with other, as yet unknown, variables to such an extent as to make the relation
      unstable in small samples.

PMID- 20034165
TI  - Time sense, emotions, and acute mental illness.
AB  - Fifty psychiatric patients were evaluated for subjective and objective changes in
      time sense in the Emergency Department and, on the average, nine days after
      admission to the hospital. Unpleasant affect (anxiety, aggression, and
      depression) was positively correlated with changes in time sense, and changes in
      pleasantness were negatively correlated with changes in time sense. There was
      greater distortion of time sense in the E.D., when unpleasant affect was greater.
      Besides the pre-post correlations of time sense with emotional changes, the
      comparison of sub-groups showed that patients with poor reality testing
      (psychotic, schizophrenic, and delusional patients) had the most marked
      distortions of time sense. These findings suggest that, in acute mental illness,
      changes in time sense may be a useful index to alterations in reality testing and
      emotion.

PMID- 20034166
TI  - The effect of partial REM sleep deprivation and delayed recovery.
AB  - Four young adult subjects each slept ten consecutive nights in the laboratory
      without awakenings. The mean nightly REM sleep time was calculated for each
      subject and used as the baseline value for further procedures. Two subjects were
      allowed 75 per cent of their baseline REM sleep time for nineteen consecutive
      nights and slept without disturbance for the next five (recovery) nights. The
      first recovery nights were 54 per cent and 13 per cent respectively above the
      baseline with a more or less exponential decline to the basal level on subsequent
      nights. The compensatory rises in REM time were compatible with what might have
      been expected following five nights of complete deprivation and suggest that
      partial REM deprivation has a cumulative effect roughly proportional to the
      degree of partial deprivation. The other two subjects underwent complete REM
      sleep deprivation for five consecutive nights followed by five nights upon which
      REM sleep time was held to the baseline level. The next five nights were
      undisturbed and the REM sleep fraction was elevated 100 per cent and 66 per cent
      respectively above the baseline. These results suggest that the REM sleep
      deprivation effect can be reversed only by extra amounts of REM sleep and will
      persist if such compensation does not take place.

PMID- 20034167
TI  - Effects of child rearing by schizophrenic mothers.
AB  - In an attempt to assess the effect of child rearing by schizophrenic mothers, two
      groups of 25 children born to schizophrenic mothers were studied. One group was
      reared by their mothers; the other group was reared from an early age by agents
      without a history of psychiatric illness. The groups were matched individual to
      individual for sex, age, and socio-economic status. The procedures employed
      included a psychiatric interview, a school report questionnaire, a word
      association test, an adjective check list, and psychophysiological
      responsiveness, recovery, and generalization testing. It was predicted that the
      mother-reared children would display greater maladjustment on the various
      measures than would the reared-apart children. The results failed to support the
      hypothesis. Those indices which discriminated between the groups at the five per
      cent level of significance indicated that: (a) the mother-reared children were
      more asocial in the classroom setting and withdrawn in general, and were also
      relatively unresponsive to social rewards; (b) the reared-apart children were
      more easily overtly upset or irritated, and displayed greater psychophysiological
      responsiveness to stress. These differences were interpreted within the context
      of an approach versus avoidance classification of orientations to the
      environment. The mother-reared children were considered to be avoidance oriented,
      and the reared-apart children approach oriented. It was concluded that rearing by
      a schizophrenic mother may have less to do with the child's level of adjustment
      than with the direction of its basic orientation to the world.

PMID- 20034168
TI  - The offspring of schizophrenic couples.
AB  - Previous studies of the psychiatric fate of children with two schizophrenic
      parents were summarized. The morbid expectancy rate was estimated to be about 35
      per cent. An hypothesis of benign modifying genes to explain the low expectancy
      was examined but failed to find support. The possibility that the hypothesized
      schizophrenic gene in double dose might lead to increased perinatal mortality was
      considered, but the relevant data suggest that noxious influences on the fetus,
      caused by schizophrenic concomitants in the mother during pregnancy, were more
      probable contributors to the perinatal mortality.

PMID- 20034169
TI  - Brain amines and emotional stress.
AB  - Evidence is presented that emotional stress in the mouse, guinea pig, and rat are
      associated with 10-30 per cent decrements in brain norepinephrine. This does not
      appear to be primarily a function of muscular activity and is probably a
      neurochemical concomitant of the 'emotional' upset. It is a generalized
      phenomenon that occurs in cortex, subcortex, cerebellum, hypothalamus, and brain
      stem, to approximately the same degree. Under these circumstances the
      concentration in brain of serotonin, gamma-aminobutyric acid, and dopamine remain
      stable. It appears that decreases of brain norepinephrine may be a component of a
      general response to intense, emotional distress.

PMID- 20034170
TI  - Oxazepam in the treatment of anxiety states: a controlled study.
AB  - Twenty-six psychoneurotic inpatients received oxazepam (60-120 mg daily) or
      placebo for one to two weeks. The strongest evidence for the superiority of
      oxazepam over placebo was that a greater proportion of oxazepam-treated patients
      remained on the study the full two weeks than placebo-treated patients. Patients'
      self-evaluations on the MMPI also favored oxazepam. Behavioral ratings by
      clinicians and ward personnel on the BPRS, symptom checklist, and assessment of
      global disorder did not discriminate the active drug from placebo as well as self
      ratings did. Most of the differences found favored oxazepam, although some failed
      to reach acceptable levels of significance. It is suggested that the relative
      similarity of neurotic individuals to normal individuals with respect to
      pathology (e.g. anxiety, tension, depression) and difficulties in life and that
      the subjectivity of experience and the absence of gross and easily demonstrable
      symptoms make evaluation of improvement difficult. Symptom measurement on
      behavioral rating devices is probably less effective in discriminating drug
      placebo differences in neurotic syndromes than in psychotic syndromes.

PMID- 20034171
TI  - The clinical laboratory and electroencephalographic effects of lithium.
AB  - Eleven patients (six manic, five non-manic) were studied during administration of
      lithium carbonate. All patients manifested neutrophilia during administration and
      there was a tendency for elevation in the fasting blood sugar. Serial EEG
      examinations and lithium determinations were done throughout the study in nine
      patients. The records of all nine patients showed profound changes in the form of
      diffuse slowing, widening of the frequency spectrum, potentiation and
      disorganization of background rhythm. Sensitivity to hyperventilation and
      paroxysmal bilaterally synchronous delta activity were also noted. Potentiation
      of an epileptic focus was observed in the EEG of one patient. These findings
      indicate that the CNS effect of lithium is both cortical and subcortical.

PMID- 20034172
TI  - The systolic blood pressure response of depressed patients to infused
      norepinephrine.
AB  - In an unselected group of thirty-eight depressed patients it was found that
      clinical recovery was positively correlated with an enhanced systolic blood
      pressure response to infused NE. All forms of physical treatment employed
      resulted in high recovery rates and high rates of NE potentiation as compared
      with a placebo group. Patients who showed a low (below the median) initial NE
      response showed higher recovery rates and higher rates of NE potentiation when
      given a somatic treatment than did patients with a high initial NE response.

PMID- 20034173
TI  - Longitudinal study of periodic catatonia. Long-term clinical and biochemical
      study of a woman with periodic catatonia.
AB  - A woman with periodic catatonia had a 600-day metabolic study. The results were
      analyzed by harmonic analysis. Her periodic stupors showed a regular 36-day
      rhythm apparently related to a 24-day menstrual cycle; but the rhythm persisted
      when menstrual function was blocked by continuous Enovid (norethynodrel +
      mestranol) administration. During the menstrual block, weight, sodium balance,
      magnesium and 17-ketosteroid (17-KS) excretion gave indications of 12- and 36-day
      fluctuations. Further studies on steriod excretion indicated that similar
      fuctuations in 17-KS output occurred when the patient was menstruating normally.
      The peaks of the 12-day cycle coincided with menses and the mid-menstrual phase;
      while the peak of the 36-day cycle coincided with the onset of stupor. 17
      hydroxycorticosteroid (17-OHCS) excretion had a 36-day cycle which lagged 4 days
      behind the 36-day 17-KS cycle. There were no indications of a 12-day 17-OHCS
      cycle. In the discussion it is suggested that the 17-KS fluctuations may partly
      reflect gonadotrophin activity rather than being exclusively due to ACTH. It is
      noted that Enovid may block only LH activity not total gonadotrophins. It is
      speculated that there may be a relationship between gonadotrophin activity and
      the psychic disturbance.

PMID- 20034175
TI  - Mental illness in parents of phenylketonuric children.
AB  - (1) This paper presents the results of a field study designed to investigate the
      hypothesis that persons presumed heterozygous for phenylketonuria are more
      vulnerable to mental disorder than other persons. Three-hundred-and-thirty-one
      persons were interviewed, including 108 parents of phenylketonuric offspring, 102
      parents with non-phenylketonuric mentally retarded offspring, and 121 parents of
      children with cystic fibrosis. (2) Information was collected by means of a
      standard interview schedule which inquired into mental health problems of the
      interviewees as well as their parents and siblings. Interviews were coded
      according to an explicit code. Mental Health was evaluated by a set of indices
      constructed by assigning numerical values to certain items in the code and
      summing related items. These indices served as operational definitions of mental
      illness. (3) Analysis of variance was used to evaluate data derived. (4)
      Decreasing social class appeared to be associated with increasing scores on the
      indices. In addition, men and women scored significantly differently on many of
      the indices. In general, differences due to sex and social class were in the
      direction which would have been expected if the indices had been measuring the
      problem areas we were trying to evaluate. (5) The parents of phenylketonuric
      children did not score differently from the other two groups, indicating that
      they were not more susceptible to mental health problems than the controls, at
      least as measured by our operational definitions. (6) Some of the problems
      associated with field studies of psychiatric disease are discussed.

PMID- 20034174
TI  - The relationship between cyclic changes in thyroid function and behavior of cats
      with brain stem lesions.
AB  - Behavioral and thyroid-states were monitored in sixteen cats for 20 months. Six
      of the cats had stereotaxic lesions of the ventro-lateral parts of the brain
      stem; these six cats exhibited periodically an abnormal behavioral state that
      consisted of the tactile elicitability of 'grooming fragments'. The onsets of the
      abnormal behavioral state occurred at variable intervals after the surgery,
      appearing mostly in the fall of the year. The other ten cats were controls and
      never exhibited the abnormal behavioral state. The thyroid-state was monitored
      during the 20-month period by determining the percentage urinary excretion of an
      injected dose of 131I. Lesioned cats retained more 131I during their abnormal
      behavioral state. The 20 months of 131I-retention data were fitted with a Fourier
      curve, and an analysis of variance was made of the fit. An annual cycle as well
      as higher frequencies were found for both control and lesioned cats, with the
      lesioned cats exhibiting more fluctuations than the normals. The main reason for
      the higher 131I-retention of the lesioned cats during their abnormal behavioral
      state was the occurrence of the abnormal behavioral state in the fall during the
      principal maximum of the thyroid-cycle. The difficulties in interpreting data
      obtained on periodic variables are discussed, and possible mechanisms whereby
      brain stem lesions bring about changes in thyroid-function are briefly reviewed.
      The results are compared to some data on periodic catatonia, and the importance
      of understanding the mechanisms of control and regulation of periodic variables
      in understanding behavior is noted.

PMID- 20034176
TI  - Sex as a source of heterogeneity in a mental health survey.
AB  - We have presented a series of constructs which were developed to measure the
      relative mental health of the members of three small populations. These
      constructs were highly concrete, and each of the 331 respondents investigated
      could be assigned a numerical rating without the use of clinical judgements of
      trained personnel. These constructs proved to be intercorrelated to a large
      degree. It was demonstrated that the size of the correlation between constructs
      was not always an accurate reflection of relationships within the population, so
      that certain relationships which were highly significant for men proved to be
      insignificant for women, and vice versa. The heterogeneous nature of the
      population could be shown to lead to two kinds of errors when data was looked at
      only for the population as a whole. (1) Loss or diminution of relationships which
      were true for one group but not the other; (2) errors in the interpretation of
      the significance of a relationship. It was pointed out that these errors probably
      represent general difficulties in the analysis of data from psychiatric studies.

PMID- 20034177
TI  - Controversy resurfaces.

PMID- 20034178
TI  - Positive ID. Medical device standard looming.
AB  - After much work and research, the Food and Drug Administration is preparing to
      publish a proposed rule for unique device identifier (UDI) standards for medical
      devices. The UDI would be used to identify a vast array of medical products and
      would streamline the hospital supply chain while improving patient safety. For
      instance, having a UDI in place would assist product recall efforts. But getting
      hospital supply chain leaders, manufacturers, group purchasing organizations and
      others to embrace UDI standards won't be easy. Here's a look at what's ahead.

PMID- 20034179
TI  - Get a grip on navigating surgical glove choices.
AB  - The wide range of surgical gloves available can make choosing the correct
      products for staff a difficult process. Add in other factors such as performance,
      allergy considerations, user preferences and cost, and making the right choice
      can get complicated. Fortunately, there are ways to simplify the process. Here
      are essential factors to consider when selecting surgical gloves so that you meet
      the criteria that are important to everyone involved.

PMID- 20034180
TI  - Get your OR organized.
AB  - Too often projects aimed at bringing permanent order to the way OR supplies are
      stored and accessed turn out to be little more than glorified cleaning exercises.
      To get the long-term results you're seeking, consider using lean management
      principles and focusing on process improvements. This requires taking a broader
      view of why and how supplies are stored the way they are. The five-step process
      outlined here provides a framework for achieving lasting, sustainable results and
      covers everything from standardizing work areas to eliminating excess product
      storage.

PMID- 20034181
TI  - Reducing risks of bloodstream infections.

PMID- 20034182
TI  - Hand hygiene focus yields visible results.

PMID- 20034183
TI  - Everyone benefits from vaccinations.

PMID- 20034184
TI  - Points to consider: The research ethics consultation service and the IRB.

PMID- 20034185
TI  - Voluntariness of consent to research: a preliminary empirical investigation.

PMID- 20034187
TI  - Character disposition and behavior type: influences of valence on preschool
      children's social judgments.
AB  - The authors studied the influences of valence information on preschool children's
      (n = 47) moral (good or bad), liking (liked or disliked by a friend), and
      consequence-of-behavior (reward or punishment) judgments. The authors presented 8
      scenarios describing the behavior valence, positive valence (help, share),
      negative valence (verbal insult, physical aggression), and disposition valence
      (nice or mean) of characters in social interaction with a friend. Overall,
      character disposition and behavior valence significantly influenced children's
      judgments. Moral, liking, and consequence-of-behavior judgments varied
      significantly by character disposition for both positive behavior scenarios. In
      contrast, there were fewer significant findings as a function of character
      disposition for negative behavior scenarios, suggesting that the negative
      behavior cue somewhat diminished the effect of character disposition on
      children's judgments. The authors discuss preschool students' coordination of
      information about valence of behavior and character disposition and the students'
      reluctance to judge that misbehavior warrants punitive consequence.

PMID- 20034186
TI  - Possible insomnia predicts some risky behaviors among adolescents when
      controlling for depressive symptoms.
AB  - This study investigated whether previously reported links between sleep and risk
      taking among adolescents (E. M. O'Brien & J. A. Mindell, 2005) are associated
      concurrently, longitudinally, or both-with sleep or underlying depression. The
      present study analyzed data from a nationally representative sample of 4,353
      adolescents in the United States who had participated in Waves I and II of the
      National Longitudinal Study of Adolescent Health (J. R. Udry, 1998). In the
      present study, grade, gender, depressive symptoms, and possible insomnia served
      as predictor variables to calculate the odds ratios for 4 categories of risky
      behaviors. After the authors accounted for other predictors, possible insomnia
      significantly predicted smoking, delinquency (within each wave but not
      longitudinally), and drinking and driving (Wave II and longitudinally). Possible
      insomnia may contribute to some types of risky behaviors over the effects of
      depressive symptoms.

PMID- 20034188
TI  - Parental relationships, autonomy, and identity processes of high school students.
AB  - To examine the interrelations among parental relationships, emotional autonomy,
      and identity statuses, the authors asked 234 (105 male, 129 female) high school
      students to complete the Parental Bonding Scale (G. Parker, H. Tupling, & L. B.
      Brown, 1979), Emotional Autonomy Scale (L. D. Steinberg & S. B. Silverberg,
      1986), and Extended Objective Measure of Ego Identity Scale-II (L. D. Bennion &
      G. R. Adams, 1986). There continues to be controversy about whether adolescents'
      identity formation is related to their emotional separation from their parents.
      According to Eriksonian and neo-Eriksonian theory (J. E. Marcia, 1980, 1984),
      adolescents who are successful in resolving their identity issues are better able
      to emotionally individuate from their parents. That is, adolescents have fewer
      conflicts with parents as they become more independent of them. Results of the
      present study indicate that adolescent perceptions of mother's caring behavior,
      but not father's caring behavior, predicted higher foreclosure identity status
      scores among adolescents. In addition, 2 dimensions of emotional autonomy (i.e.,
      perceiving parents as people and parental deidealization) best predicted the
      adolescent identity statuses of moratorium and foreclosure. Results also indicate
      that future research may need to establish a better theoretical conceptualization
      of the constructs of interest in this study and better measures of emotional
      autonomy among adolescents.

PMID- 20034189
TI  - Sociometric stability and the behavioral correlates of peer acceptance in early
      childhood.
AB  - The author presents findings from an Australian study examining the behavioral
      correlates and stability of social status among preschool-aged children. Using
      sociometric assessment, the author determined the social status of an initial
      sample of 187 preschool-aged children (94 boys, 93 girls; M age = 62.4 months, SD
      age = 4.22 months). The author observed children (N = 70) who were classified as
      rejected, neglected, or popular. For a total of 25 min during a 3-month period,
      the author observed children engaging in free play in their preschool centers.
      Results indicate that children classified as popular were more likely to engage
      in cooperative play, engage in ongoing connected conversation, and display
      positive affect, compared with those classified as rejected or neglected. Popular
      children were less likely than rejected children or neglected children to engage
      in parallel play, onlooker behavior, or alone-directed behavior. To test for
      stability and change, the author repeated sociometric interviews 6 months after
      initial sociometric classification. Results indicate that preschool-aged
      children's social status classifications showed a moderate to high rate of
      stability for those children classified as popular, rejected, or neglected.

PMID- 20034191
TI  - Suicide prevention strategies and mental disorders.

PMID- 20034190
TI  - Do alcohol expectancy outcomes and valuations mediate peer influences and
      lifetime alcohol use among early adolescents?
AB  - Building on the theory of reasoned action (I. Ajzen & M. Fishbein, 1973, 1980; M.
      Fishbein & I. Ajzen, 1975) and expectancy theory, the authors examined the
      mediating role of alcohol expectancies in adolescent drinking behaviors by
      testing whether alcohol expectancy outcomes and valuations (the extent to which
      these outcomes are perceived as good or bad) mediate the association between peer
      influences and lifetime alcohol use. Early adolescents (N = 904) from 2 public
      middle schools in western Michigan completed a battery of questionnaires.
      Overall, results showed that alcohol expectancies and valuations partially
      mediated the relations between peer influences (peer use and peer approval) and
      lifetime alcohol use. The findings suggest that associating with peers who are
      perceived as using alcohol and approving of drinking may influence adolescents'
      alcohol expectancies. The authors briefly discuss future research directions and
      implications for prevention.

PMID- 20034192
TI  - The role of psychopharmacology in suicide prevention.
AB  - The potential role of psychopharmacology in suicide prevention is often
      minimised. This may to some extent reflect that few medication trials have
      specifically focussed on prevention of suicidal behaviour--indeed this outcome is
      often not reported in trials. However, there is reasonably strong evidence that
      lithium may reduce risk of suicide, the postulated mechanism being a specific
      effect on aggression. Evidence is lacking with regard to any protective effect of
      other mood stabilizers. Clozapine may reduce suicidal behaviour in patients with
      schizophrenia, with reduction of affective symptoms being a possible explanation.
      The role of antidepressants in relation to suicide risk is highly controversial,
      especially in children and adolescents. It is unclear whether minor
      tranquillizers or hypnotics can assist in suicide prevention, although they can
      reduce the anxiety symptoms that may occur during initial treatment with SSRI
      antidepressants. It is also uncertain whether psychopharmacology has a role in
      preventing suicidal behaviour in people with personality disorders. Despite the
      limitations of the evidence we contend that suicide risk should be an important
      factor in deciding when and what to prescribe.

PMID- 20034193
TI  - Long-term lithium treatment in the prevention of suicidal behavior in bipolar
      disorder patients.
AB  - We reviewed available research findings, including meta-analyses on effects of
      lithium-treatment associated with rates of suicidal behavior in bipolar disorder
      or unipolar major depressive disorder patients, and for comparisons of lithium to
      mood-stabilizing anticonvulsants. Data from meta-analyses consistently indicate
      marked reductions of suicidal behavior and mortality during long-term treatment
      with lithium salts in bipolar disorder patients, and possibly also in unipolar,
      recurrent major depressive, perhaps even more effectively than with
      anticonvulsants proposed as mood-stabilizers. Suicidal risk is frequently
      associated with dysphoric-agitated symptoms, anger, aggression, and impulsivity
      all of which may respond better to treatment with lithium or other mood
      stabilizing medicines than to antidepressants. In these conditions,
      antidepressant treatment may not provide a beneficial effect on risk of suicidal
      thoughts and perhaps attempts, particularly in juveniles, whereas, lithium,
      perhaps even more than anticonvulsants, seems to be remarkably effective in the
      preventing suicidal behavior. The mechanism of action is not well defined and may
      be associated with either a prevention of mood recurrences or a more specific
      "antisuicidal" activity.

PMID- 20034194
TI  - Clinical challenges in the assessment and management of suicidal behaviour in
      patients with bordeline personality disorder.
AB  - Self-injurious and suicidal behaviours are highly prevalent in patients with
      borderline personality disorder (BPD) and the risk of completed suicide is high.
      Borderline patients often present with heterogeneous clinical pictures and
      widespread comorbidity complicating clinical assessments and management. This
      calls for increased efforts in systematic evaluation and monitoring of self
      harming and suicidal behaviours; these behaviours should be addressed actively as
      high priority treatment targets. Early drop-out is common for BPD patients in
      treatment but is possible to counteract by fostering a strong therapeutic
      relationship through adopting a realistic, but consistent and supportive approach
      carefully avoiding reinforcement of suicidal behaviours. Suicidal crises should
      primarily be managed in an outpatient setting giving priority to keeping the
      patient safe adopting a safety plan procedure, while helping the patient as
      quickly as possible to return emotionally to a more acceptable level of arousal
      and mental functioning. Pharmacological treatments should primarily be used for
      management of comorbid conditions, but may possibly also be helpful when used to
      reduce specific symptoms such as anger, hostility and impulsivity. There is
      currently a range of different integrated short-term and long-term psychological
      treatments in different stages of development and some of them have been shown to
      be efficacious in reducing suicidal behaviours; notably dialectical behaviour
      therapy and mentalization-based therapy.

PMID- 20034195
TI  - What is a randomised controlled trial?

PMID- 20034196
TI  - Twin studies in psychotic disorders.

PMID- 20034197
TI  - Diet, smoking and cardiovascular risk in schizophrenia in high and low care
      supported housing.
AB  - BACKGROUND: People suffering from schizophrenia have markedly increased physical
      morbidity and mortality. A poor diet and sedentary lifestyle make a significant
      contribution to this ill health. Healthcare professionals need to include
      assessments of diet and to promote a 'healthy living' lifestyle. AIMS: To
      describe the dietary habits and cardiovascular risk factors of people with
      chronic schizophrenia living in supported accommodation and to audit the
      provision of cardiovascular health screening in this population. METHOD: The
      dietary habits of 69 people with chronic schizophrenia living in community
      settings were assessed. Tobacco smoking, body mass indices and waist
      circumference were also measured. The dietary behaviour of patients living in
      high care settings with care staff present every day was compared with those in
      low care settings. RESULTS: Residents in both levels of care made poor dietary
      choices. Patients in high care were consuming more fast food than those in low
      care. The dietary habits of men and women in both levels of care were worse than
      reported by surveys of the general population in England. All patients had seen
      their GP in the previous year though only 3 had received diabetes screening and
      fewer than half had lipid profiles. CONCLUSIONS: People with schizophrenia do not
      improve their diet just by the provision of healthy food as was the case in high
      care settings. Secondary care services must address physical health monitoring as
      well as mental health if the increased mortality of patients with schizophrenia
      is to be addressed effectively. More effective interventions are necessary to
      improve and sustain a healthy diet.

PMID- 20034198
TI  - Strange bedfellows: economics, happiness and mental disorder.
AB  - AIM: The high economic and social costs associated with the 'common mental
      disorders', and the need to scale up appropriate care services, are now widely
      recognized, but responses vary from country to country. In Britain, a current
      government initiative to promote psychological therapy is driven both by economic
      pressures and by research on the factors of happiness, or life-satisfaction. This
      article provides a short critical review of the project. METHOD: A health policy
      analysis, with regard to problem definition; objectives; sources of information;
      criteria for evaluation; impact on existing services, and comparison with
      alternative strategies. RESULTS: The new programme, Improving Access to
      Psychological Therapies (IAPT), aims to expand treatment services by training
      3,600 'psychological therapists' in cognitive behavioural therapy (CBT), which
      they will then apply in the wider community. This service, with an initial budget
      of 173 million pounds sterling, will provide treatment for depression and chronic
      anxiety from local centres across the country. The programme is intended to pay
      for itself by reducing incapacity costs. Closer examination, however, raises
      questions concerning the project's theoretical basis, logistics and research
      methodology, and casts doubt on its advantages over alternative approaches.
      CONCLUSIONS: The IAPT project is ill-designed to achieve its objectives and
      unsuitable as a model for treatment and care of the common mental disorders in
      other countries. An alternative strategy, based on closer integration of
      community mental health and primary health care, should be tested and on previous
      experience seems likely to prove more cost-effective.

PMID- 20034199
TI  - [Prevalence and risk factors of postnatal depression among women attending
      antenatal courses].
AB  - AIMS: Postnatal depression, the most frequent complication occurring after
      pregnancy, is often not recognized. The prevalence of postnatal depression is
      currently considered to be 10-15% in western countries. A wide range of risk
      factors related to postnatal depression were researched in international studies.
      Our aim was to evaluate the risk factors and their frequency in a women
      population of Bergamo Province and compare the results with findings of
      international literature. METHODS: 595 women taking part to antenatal courses in
      three hospitals in Bergamo Province were screened for Postnatal Depression using
      EPDS and clinical interview. Prevalence and possible psychosocial risk factors
      data were collected and subsequently analysed and compared with literature
      findings. RESULTS: Thirty six (7.1%) women of our sample had postnatal
      depression. Depressed mood and depression during pregnancy, anxiety during
      pregnancy, poor social support, recent life events, a history of depression or
      other psychiatric history, presence of maternity blues were the strongest
      predictors of postnatal depression in our sample. CONCLUSIONS: The Psychosocial
      risk factors emerged from our study are substantially the same indicated by
      international studies, on the contrary prevalence is a little lower. This result
      may be explained considering that our women sample wasn't completely
      representative of general population.

PMID- 20034200
TI  - Stressful and intrusive life events preceding first episode psychosis.
AB  - AIM: To test the hypothesis that stressful life events, in particular intrusive
      events, would cluster before the first onset of psychosis. METHO: Forty-one
      patients with first episode psychosis were interviewed with the Life Events and
      Difficulties Schedule to assess events in the year before the onset of illness.
      Events were rated contextually on timing, independence, threat, and
      intrusiveness. Within-patient group clustering was evaluated, and the patient
      group was compared with two general population surveys from London. RESULTS:
      Events were very frequent in the year before the onset of psychosis. Stressful
      and intrusive events were more common in the three months before onset compared
      with the previous nine months, although few analyses reached conventional
      statistical significance. Threatening and intrusive events were much more
      frequent in patients than in the comparison groups. First episode psychosis
      patients were strikingly more likely to report an intrusive event in the three
      months before onset (OR=17.1, 34% v 3%), and also showed an excess between three
      months and one year before onset (OR=8.1, 11% v 3%). CONCLUSIONS: Events may
      trigger many cases of first episode psychosis. The effect emerges several months
      before onset, particularly if the events are intrusive. This has both theoretical
      and clinical implications.

PMID- 20034201
TI  - The relationship among mental health status (GHQ-12), health related quality of
      life (EQ-5D) and health-state utilities in a general population.
AB  - AIM: To assess the relationship between mental health and health-related quality
      of life (HRQL) in the general population, and to map GHQ-12 as a screening test
      for population psychological distress to a generic health state measure (EQ-5D)
      in order to estimate health state values and allow deriving quality-adjusted life
      years. METHODS: Relationship between mental health and HRQL was examined from the
      2004 Canary Islands' Health Survey. Participants were classified as probable
      psychiatric cases according to GHQ-12. HRQL was measured by the EQ-5D index.
      Multivariate lineal regression analysis was used to examine the association
      between mental health and HRQL adjusting by socio-demographic variables and
      comorbidities. A multivariate regression model was built from EQ-5D to estimate
      health states values using GHQ-12 as exposure. RESULTS: EQ-5D index scores
      decreased as the GHQ-12 scores increased. Clinical and socio-demographic factors
      influenced HRQL without changing the overall trend for this negative
      relationship. The regression equation explained 43% of the variance. For
      estimation of utility scores, the model showed a high predictive capacity, with a
      mean forecast errors of 16%. CONCLUSIONS: HRQL progressively decreased when the
      probability of being a psychiatric case increased. Findings enable health state
      values to be derived from GHQ-12 scores for populations where utilities has not
      or cannot be measured directly.

PMID- 20034202
TI  - Is the exposure to antidepressant drugs in early pregnancy a risk factor for
      spontaneous abortion? A review of available evidences.
AB  - AIM: To review studies conducted to establish the risk of spontaneous abortion
      (SA) in women exposed to antidepressant drugs (ADs) during early pregnancy.
      METHODS: By using different search terms, PubMed, Toxline, EMBASE, PsychINFO, and
      the Cochrane library databases were searched from January 1980 to March 2008, to
      identify studies assessing the risk of SA in women exposed to different classes
      of ADs during the first trimester of pregnancy. RESULTS: Ten studies over 21
      identified were selected for the analysis. All were performed prospectively and
      included as control group unexposed women, or exposed to non-teratogenic drugs or
      to placebo. In seven studies a depressive episode was specified as the reason for
      which the drug was prescribed, while the time of exposure was in nine.
      CONCLUSIONS: Only three studies over ten selected reported a significant
      association between an increased rate of SAs and early pregnancy exposure to some
      ADs. Many methodological flaws in the study design were found in all studies
      considered. Given this background and a lack of strong evidence on this issue,
      further prospective and better designed studies are needed to assess the risk of
      SA in pregnant women exposed to ADs against the risk of an untreated maternal
      depression.

PMID- 20034203
TI  - Patterns of benzodiazepine use in a Canadian population sample.
AB  - AIM: The objective of this study was to identify clinical and demographic factors
      that may be associated with benzodiazepine treatment, to describe the reported
      reasons for use of these medications and to appraise the pattern of use in
      relation to standard guidelines in a general population sample. METHODS:
      Telephone survey methods were employed to select a sample of 3345 people between
      the ages of 18 and 64. A computer assisted telephone interview, including the
      Mini Neuropsychiatric Diagnostic Interview (MINI), was administered. Estimates
      were weighted for design features and population demographics. RESULTS: The
      overall prevalence of benzodiazepines use was 3.3% (95% confidence interval [CI]
      2.6 to 4.1%). There was a higher frequency of medication use in women than men,
      among respondents who were widowed, separated or divorced, and those with lower
      levels of education. In relation to MINI diagnosis, diagnoses of Panic Disorder
      and Major Depression increased the probability of taking benzodiazepines. The
      reported main reason for use was "Sleep disorders" (68.9%), "Anxiety" (35.8%),
      "Depression" (27.8%) and "Pain management" (21.2%). More than 80% of subjects
      were taking benzodiazepines for more than one year. CONCLUSIONS: When compared to
      previous estimates, the lower frequency of benzodiazepines use suggests that
      there has been improvement in their evidence-based use at a population level.
      However our results once more confirm the difficulty stopping the use of these
      medications once they have been started. Further randomized control studies may
      help clinicians in having a better practical approach to rational benzodiazepine
      use.

PMID- 20034204
TI  - [Quality of life of relatives of patients with obsessive-compulsive disorder:
      relation to family accommodation and other socio-demographic and clinical
      characteristics].

PMID- 20034205
TI  - Mental health care of children and adolescents in Serbia: past steps and future
      directions.

PMID- 20034206
TI  - The effect of phytohormones on safflower regeneration plant.
AB  - OBJECTIVE: To study the effect of phytohormones on the regeneration of safflower,
      in order to provide a foundation for the rapid propagation of safflower seeds and
      genetic transformation. METHODS: The experiment used the cotyledons as the
      explant and studied the influence of calli induction, differentiation and rooting
      by phytohormones. RESULTS: 1. Different hormones by single using induced calli,
      but didn't directly produce adventitious buds; 2. With the combination of
      different phytohormones on the differentiation of adventitious buds were
      significantly different, the roots were also significantly different; 3.
      Cotyledon calli induction medium: MS + 3% Sucrose + 0.7% Agar + 1.0 mg/L NAA;
      differentiation medium: MS + 3% Sucrose + 0.7% Agar + 0.2 mg/L NAA + 1.0 mg/L 6
      BA; rooting medium: 1/4 MS + 2.0 mg/L NAA + 0.5 mg/L IAA. CONCLUSION: We have
      screened out the best culture medium of calli induction, differentiation and
      rooting via using singularity phytohormone and two phytohormones.

PMID- 20034207
TI  - [Optimization of culture conditions for crown gall of Panax quinquefolium and the
      content determination of their polysaccharides].
AB  - OBJECTIVE: To optimize the culture conditions and determine the content of
      polysaccharides in crown gall of Panax quinquefolium. METHODS: The orthogonal
      design was used for the optimization of culture condition (such as media,
      inoculum amount, pH and the content of inorganic elements in media) and their
      effects on the polysaccharides content. RESULTS: (1) The crown gall tissue could
      grow and produce polysaccharides in MS (Murashige & Skoog) solid medium without
      any hormones; (2) The time-dependent regularity of the growth amount and
      polysaccharides content of the crown gall tissue in MS solid medium was
      approached: polysaccharides content was the highest in 21 d and biomass achieved
      to the greatest in 24 d; (3) The polysaccharides content and growth amount were
      the highest when pH 5.6 of media; (4) The inoculation of 4 - 7 g (FW/flask) was
      comparatively advantage to the growth of the crown gall, but no effect on
      polysaccharides content. CONCLUSION: This method can be used to accumulate the
      high contents of polysaccharides in crown gall cultures of P. quinquefolium.

PMID- 20034208
TI  - [Anticoagulative effect and antiplatelet aggregation effect of combination of
      Hirudo and Tabanus on rat model of blood stasis syndrome].
AB  - OBJECTIVE: To observe anticoagulative effect and antiplatelet aggregation effect
      of the combination of Hirudo and Tabanus with different dose-ratio on rat model
      of blood stasis syndrome. METHODS: The rat model of blood stasis syndrome was
      established by subcutaneous injection of adrenaline combined with stimulation of
      icy water. Then prothrombin time (PT), activated partial thromboplastin time
      (APTT), fibrinogen (FIB) contents and inhibition rate of blood platelet
      aggregation were determined. RESULTS: Platelet aggregation increases, APTT and PT
      reduced, and FIB contents increased in model control group significantly
      (P<0.001). Hirudo, Tabanus and the combination of Hirudo and Tabanus had
      antiplatelet aggregation effect in varying degrees. APTT and PT were prolonged
      significantly (P<0.05 and P<0.01, respectively) in Hirudo group, Tabanus group
      and combination groups, especially in the group with dose-ratio of Hirudo to
      Tabanus being 4:3. FIB contents decreased significantly in combination group with
      dose-ratio being 3:1 (P<0.05). CONCLUSIONS: The combination groups of Hirudo and
      Tabanus have better effect of anticoagulation and antiplatelet aggregation than
      Hirudo group and Tabanus group. While in the four combination groups, the group
      recommended by classical TCM monograph with dose-ratio of Hirudo to Tabanus being
      4:3, has the best anticoagulation effect.

PMID- 20034209
TI  - [RAPD analysis and construction of specific DNA probes between Pinellia ternata
      and Typhonium flagelliforme].
AB  - OBJECTIVE: To establish a molecular marking method to identify Pinellia ternata
      and Typhonium flagelliforme. METHODS: Twenty-two random oligonucleotide primers
      were used in RAPD analysis on the genomic DNA of two types of Pinellia ternata in
      Sichuan and two types of Typhonium flagelliforme in Guangxi. The special
      fragments were sequenced, marked as probes and then conducted Southern blot.
      RESULTS: A great deal of special bands was found between Pinellia ternata and
      Typhonium flagelliforme. A Pinellia ternata specific molecule was screened.
      CONCLUSION: RAPD analysis and specific DNA probes show potential value in the
      identification of Pinellia ternata and Typhonium flagelliforme.

PMID- 20034210
TI  - [Studies on the chemical constituents of Coleus forskohlii].
AB  - OBJECTIVE: To study the chemical constituents in the aerial parts of Coleus
      forskohlii. METHODS: The compounds were isolated by various column
      chromatographic methods, and their structures were identified by spectroscopic
      methods. RESULTS: Twelve compounds were isolated and identified as chamaecydin
      (1), 6 alpha-hydroxydemethylcryptojaponol (2), alpha-cedrene (3), oleanolic acid
      (4), forskolin G (5), forskolin J (6), 1,6-diacetyl-9-deoxyforskolin (7),
      forskolin A (8), forskolin H (9), 6-acetyl-1-deoxyforskolin (10), betulinic acid
      (11), beta-sitosterol (12). CONCLUSION: Compounds 1 - 3 are isolated from Coleus
      genus for the first time, and compound 4 is isolated from C. forskohlii for the
      first time.

PMID- 20034211
TI  - [The secondary metabolites of the mangrove endophytic fungi ZZF13 and Guignardia
      sp. 4382 from the South China Sea].
AB  - OBJECTIVE: The secondary metabolites of the fungus ZZF13 isolated from the leaves
      of the mangrove sample Kandelia candel in Zhanjiang and Guignardia sp. 4382
      isolated from bark of Kandelia candel (endophyte) of Mai Po, Hong Kong were
      studied. METHODS: The compounds were isolated by siliga gel, and their structures
      were identified by IR, MS and NMR. RESULTS: Four compounds were isolated from the
      culture of this strain. Their structures were identified as Bacillpsporin C (1),
      5-carboxymellein (2), 5-methylmellein (3) and 1-(2,6-dihydroxyphenyl) butanone
      (4). CONCLUSION: The compounds 2 - 4 are isolated from the Guignardia sp. of
      Marine fungi for the first time.

PMID- 20034212
TI  - [Studies on the chemical constituents of Chaenomeles speciosa].
AB  - OBJECTIVE: To study the chemical constituents of Chaenomeles speciosa. METHODS:
      Isolation and purification were carried out by varied chromatographies, and
      structure identifications of compounds were carried out by physical methods,
      chemical methods and spectral data. RESULTS: Seven compounds were obtained from
      the ethyl acetate fraction of C. speciosa, and were identified as cinnamic acid
      (I), 2'-methoxyaucuparin (II), 2-hydroxyl-butanedioic acid-4-methylester (III),
      esculetin (IV), p-hydroxybenzoic acid (V), chlorogenic acid (VI), caffeic acid
      (VII). CONCLUSION: Compounds I - IV are obtained from Chaenomeles genus for the
      first time.

PMID- 20034213
TI  - [Studies on the chemical constituents from Euphorbia chrysocoma].
AB  - OBJECTIVE: To study the chemical constituents from the aerial part of Euphorbia
      chrysocoma. METHODS: All compounds were isolated and purified by many methods,
      including siliga gel and reversed phase RP-18 column chromatographies,
      preparative thin layer chromatography, Sephadex LH-20, and recrystallization.
      Their structures were mainly elucidated by ESI-MS and NMR spectra and their
      physical characters. RESULTS: Six compounds were isolated from the petroleum
      ether section from 75% ethanol extraction of the material. Their structures were
      identified as taraxerol (1), epitaraxerol (2), beta-sistosterol (3), beta
      sitostenone (4), jolkinolide E (5), and sesamin (6). CONCLUSION: Compounds 1, 2,
      4, 5, and 6 are isolated from this plant for the first time.

PMID- 20034214
TI  - [Studies on the isoflavonoids of Iris tectorum].
AB  - OBJECTIVE: To study the isoflavonoids of Iris tectorum. METHODS: The compounds
      were isolated by columm chromatography on silica gel and purified by Sephadex LH
      20. Structures of these compounds were elucidated by spectral analysis and
      phytochemical properties. RESULTS: Six isoflavonoids were isolated from Iris
      tectorum, which were tectoridin (I), tectorigenin (II), iristectorin A (III),
      iristectorigenin A (IV), iristectorin B (V), 5,7,4'-trihydroxy-6,3'-dimethoxy
      isoflvone (VI). CONCLUSION: Compound VI is isolated from this plant for the first
      time.

PMID- 20034215
TI  - [Studies on the chemical constituents of Sarcopyramis nepalensis].
AB  - OBJECTIVE: To study the chemical constituents of Sarcopyramis nepalensis.
      METHODS: The constituents were isolated and purified with chromatography and the
      structures were elucidated by spectral analysis. RESULTS: Ten compounds were
      isolated and their structures were identified as: (E)-1-(3,4-dihydroxy-phenyl)
      ethyl acrylate (I), stearic acid (II), palmitic acid (III), 4-hydroxybenzonic
      acid (IV), 3,4-dihydroxy benzoic acid (V), gentisic acid ( VI), gallic acid
      (VII), beta-sitosterol (VIII), daucosterol (IX), stigmasterolstearate (X).
      CONCLUSION: Compounds I , IV, V, VI, VII are isolated from this plant for the
      first time.

PMID- 20034216
TI  - [Studies on the chemical constituents in ethyl acetate extraction from the fruit
      of Polygonum orientale].
AB  - OBJECTIVE: To study on the chemical constituents in ethyl acetate extraction from
      Polygonum orientale. METHODS: By repeated silica gel chromatographic seperation
      and spectral analysis the structures were determined. RESULTS: Seven compounds
      were isolated and identified from Polygonum orientale. They were 3,5,7
      trihydrochromone (I), kaempferol (II), 5,7,4'-trihydroxydihydroflavonol (III),
      dihydroquercetin (IV), quercetin (V), p-hydroxyphenylethanol ferulate (VI), p
      hydroxyphenylethanol-p-coumaric (VII). CONCLUSION: Compounds II, III are isolated
      from this plant for the first time.

PMID- 20034217
TI  - [Studies on the chemical constituents of Schisandra pubescens].
AB  - OBJECTIVE: To study the chemical constituents of Schisandra pubescens. METHODS:
      The chemical constituents were isolated by silica gel, Prep-HPLC and Prep-TLC
      methods. And their structures were elucidated by physical-chemical and
      spectroscopic methods. RESULTS: Seven compounds were obtained and identified as
      (+)-gomisin K2 (I), gomisin S (II), Pregomisin (III), Schisantherin A (IV),
      Schicantherin B (V), Angeloylgomisin Q (VI), Rubrildilactione (VII). CONCLUSION:
      All compounds are isolated from this plant for the first time.

PMID- 20034218
TI  - [Studies on the chemical constituents of ethyl acetate extraction from Reineckea
      carnea].
AB  - OBJECTIVE: To study the chemical constituents of Reineckea carnea. METHODS: The
      compounds were isolated by extraction, silica gel and reversed phase silica gel
      column chromatography. The structures were identified by various spectroscopic
      methods including 1D and 2D-NMR spectrum, MS, IR, etc. RESULTS: Six compounds
      were isolated and identified as beta-sitosterol (1), isorhodeasapogenin (2),
      isorhodeasapogenin (3), (25S)-1beta,3beta,4beta-trihydroxyspirotan-5beta-yl-O
      beta-D-glucopyranoside (4), kitigenin-5-O-beta-D-glucopyranoside (5) and
      nicotianoside B (6). CONCLUSION: Compounds 4, 6 are obtained from this plant for
      the first time.

PMID- 20034219
TI  - [Primary study on mechanism of baicalin on the Th1/Th2 response in murine model
      of asthma].
AB  - OBJECTIVE: To study the mechanism of baicalin on the cytokines of Th1/Th2 in
      murine model of asthma. METHODS: The murine model of asthma was induced by OVA.
      Different doses of baicalin were orally administered to the mice respectively.
      The spleen cells were cultured 3 days for the measurement of IFN-gamma, IL-4, IL
      5 and IL-10 by ELISA. After 2 days of culture, the spleen cells were treated with
      Trizol for extraction of total RNA. The gene expressions of T-bet, GATA-3 and
      STAT-6 were analyzed by RT-PCR. RESULTS: The treatment with baicalin obviously
      decreased the production of IL-4 and IL-5 and the gene expression of GATA-3, STAT
      6, but increased the production of IL-10. CONCLUSION: Baicalin may modulate the
      Th1/Th2 balance mainly by altering the gene expressions of GATA-3 and STAT-6 in
      vivo and increasing the production of IL-10.

PMID- 20034220
TI  - [Effect of Dahuangzhechong pill on the gene expression spectra of preventing
      arterial thrombosis].
AB  - OBJECTIVE: To investigate the effect of Dahuangzhechong pill on the gene
      expression spectra of preventing arterial thrombosis, and reveal its mechanism on
      molecule level. METHODS: Mononuclear cell and blood platelet of the arterial
      thrombosis patients were separated before and after treatment by Dahuangzhechong
      pill. Their RNA was extracted respectively and the genes expressions were
      detected using gene array containing 14,000 gene. RESULTS: 44 genes up-expressed
      and 299 genes down-expressed in blood platelet, 252 genes expression increased
      and 299 genes expression decreased in mononuclear cell genes after treated with
      Dahuangzhechong pill. The cluster analysis showed that the genes contained ion
      channel and transport protein, apoptosis related protein, DNA synthesis, repair
      and transcription factor, cell receptor, cell signal and transducin, and protein
      translation and synthesis, etc. CONCLUSION: Dahuangzhechong pill may prevent
      arterial thrombosis through genes containing ion channel and transport protein,
      apoptosis related protein, DNA synthesis, repair and transcription factor, cell
      receptor, cell signal and transducin, and protein translation and synthesis, etc.

PMID- 20034221
TI  - [Study on the detoxification of alcohol extracts from orientvine and its
      effective component on withdrawal syndromes of morphine].
AB  - OBJECTIVE: To observe the effect of alcohol extracts from orientivne and its
      effective component sinomenine on withdrawal syndromes and neurotransmitter of
      morphine-abstinent mice and on intracellular calcium level in morphine-dependent
      neuronal-cells line. To study the detoxification of alcohol extracts from
      orientvine and sinomenine on morphine-dependent animal and explore the mechanism
      of its effect. METHODS: The effect of alcohol extracts from orientivne and
      sinomenineon on abstinent syndromes was observed by experiment study on morphine
      dependent ex vivo ileum from guinea pigs and morphine-dependent mice. The
      morphine-dependent model mice were established by injection on dosage increasing
      by degrees. The hypothalamic monomine neurotransmitters such as NA, DA, 5-HT were
      tested by fluorospectrophotometry. Morphine-dependent cell line was established
      by administering morphine at different doses into the culture medium. The cells
      were stained with fluo-3 and the intracellular calcium level was measured by flow
      cytometry. RESULTS: Alcohol extracts from orientvine and sinomenine could
      alleviate withdrawal contractile response of morphine-dependent ex vivo ileum
      from guinea pigs and withdrawal syndromes of morphine-dependent mice, decrease
      the concentration of the neurotransmitters, and elevate the intracellular calcium
      level and inhibit the decreasing of Ca2+ induced by naloxone. CONCLUSIONS:
      Alcohol extracts from orientvine and sinomenine have some effects on withdrawal
      syndromes which may be related to inhibiting neurotransmitters and the regulation
      of intracellular calcium concentration.

PMID- 20034222
TI  - [Protecting effect of Chaenomeles speciosa broth on immunosuppressive mice
      induced by cyclophosphamide].
AB  - OBJECTIVE: To investigate the effects of Chaenomeles speciosa broth on
      immunoregulation for anti-tumor chemotherapy. METHODS: Immunosuppressive model
      was induced by cyclophosphamide (CTX) in mice. The mice were treated with the
      broth for 15 days. The serum hemolysin was observed in mouse sera. Spleen
      lymphocyte transformation and gene transcription related to the immunoregulation
      in spleen lymphocytes were detected. RESULTS: After administrated the broth, the
      serum hemolysin and lymphocyte transformation rates significantly increased and
      the mRNA expression of foxp3, TGF-beta, PD1, Fas, Bax were downregulated compared
      with CTX-group. CONCLUSION: Chaenomeles speciosa broth has protective effects on
      the immunosuppressive mouse induce by CTX.

PMID- 20034223
TI  - [Extracts of mucopolysaccharides from Asterias rollestoni and its
      immunoregulation effect in vitro].
AB  - OBJECTIVE: To study immunoregulation effects on normal pulpal cells of the
      mucopolysaccharides MP1 and MP2 extracted from Asterias rollestoni body wall and
      viscera, respectively. METHODS: The orthogonal design was employed to obtain the
      best possible combination of the critical parameters for mucopolysaccharide MP2.
      MP1, MP2, glycosides, MP1 + glycosides and MP2 + glycosides were added
      respectively into pulpal cells culture media to test their effects on spleen
      cells proliferations by MTT assay. RESULTS: MP1 and MP2 could certainly increase
      the proliferation of the normal splenocyte and inhibit glycosides cytotoxicity.
      Compared with controls, MP2 reversed the cytotoxicity of glycosides at
      concentration of 25 to 40 mg/mL, the greatest activity appearing at the dose of
      40 mg/mL (P<0.01), while MP1 didn't reverse it. CONCLUSION: MP1 and MP2 can
      enhance immunity of normal mice, and MP2 can significantly reverses the
      cytotoxicity of glycosides in vitro.

PMID- 20034224
TI  - [The immunomodulatory effects of sijunzi decoction and its disassembled
      prescription on D-galactose-induced aging mice].
AB  - OBJECTIVE: To observe the immunomodulatory effects of codonopsis, atractylodes
      macrocephala, tuceahoe, broiled licorice and sijunzi decoction on D-galactose
      induced aging mice. METHODS: The models of aging mice were induced by D
      galactose, the garlands and splenic lymphocyte transformation test (MTT) were
      used to determine the ability of erythrocytes immune and lymphocytes conversion;
      The content of maleic dialdehyde (MDA), activity of superoxide dismutase (SOD)
      and glutathione pemfidase (GSH-Px) in serum were detected. RESULTS: Sijunzi
      decoction and its disassembled prescription codonopsis could significantly
      increase the ability of T lymphocyte transformation (P<0.05); Atractylodes
      macrocephala and sijunzi decoction could significantly enhance C(3b) garlands
      ratio (P<0.05) and decrease IC garlands ratio (P<0.05) on D-galactose-induced
      aging mice. Sijunzi decoction significantly increased the activity of SOD and GSH
      Px (P<0.01), and decreased the content of MDA in serum (P<0.05). CONCLUSION:
      Sijunzi decoction and its disassembled prescription codonopsis, atractylodes
      macrocephala can improve the immunomodulatory effects on D-galactose-induced
      aging mice; but tuceahoe and broiled licorice have no obvious effects.

PMID- 20034225
TI  - [Study on the preparation of sustained-release pellets containing active
      components from Gastrodia elata by fluid-bed coating].
AB  - OBJECTIVE: To study the formulation of sustained-release pellets containing
      active components from Gastrodia elata by coating in the fluid-bed. METHODS: The
      sustained-release pellets were prepared with Eudragit RS 100. The formulation was
      optimized by the direct comparison. Then their properties were evaluated.
      RESULTS: The pellets presented the perfect sphericity and narrow diameter
      distribution and the curve of their cumulative drug release was in accord with
      Higuchi equation. CONCLUSION: The pellets have sustained-release effect in 12
      hours.

PMID- 20034226
TI  - [Preparation and drug release property of paclitaxel nanoparticles].
AB  - OBJECTIVE: To prepare paclitaxel nanoparticles and evaluate its drug release
      property in vitro. METHODS: The chitosan-poly (lactide) copolymers were
      synthesized by ring-opening polymerization. Paclitaxel nanoparticles were
      prepared by the nanoprecipitation method. The encapsulation efficiency of the
      nanoparticles and the in vitro release of paclitaxel were studied. RESULTS: The
      nanoparticles were fine and uniform spheres. The encapsulation efficiency of
      nanoparticles was up to 93.2%. The in vitro release profile showed the slow and
      stable release rate of paclitaxel. CONCLUSION: This method is simple and the
      nanoparticles possess good physical performance as sustained release character in
      vitro.

PMID- 20034227
TI  - [Study on purification of total flavones from Trollius ledebouri by macroporous
      resin].
AB  - OBJECTIVE: To study the optimal technologies for the purification of total
      flavones from Trollius ledebouri with macroporous resin. METHODS: Static and
      dynamic adsorption-desorption methods were adopted to choose the optimal type of
      resin. The adsorption function of D101 macroporous resin and the effects of
      sample concentration, pH, flow rate and eluant etc. were studied. Then the
      orthogonal design L9 (3(4)) was used to select the optimum purification process
      conditions. RESULTS: The appropriate technological conditions were as follows:
      the sample concentration was 0.5 g/mL, pH 6.0, the ratio of sample to D101
      macroporous resin was 1:1 (W/W), 4 BV of water was used as purificant and 6 BV of
      30% alcohol was used as eluant. Under these conditions, the average content of
      total flavonoids extract was over 60%.

PMID- 20034228
TI  - [Study on the inclusion of volatile oil extracted from Herba Pogostemonis and
      Exocarpium citri by beta-cyclodextrin].
AB  - OBJECTIVE: To investigate the inclusion technology conditions of volatile oil
      extracted from Herba Pogostemonis and Exocarpium citri in Huxin Fang granules by
      beta-cyclodextrin. METHODS: The orthogonal design was used. The percent
      conversion of the oil in inclusion and the yield of inclusion complex were the
      indices to determine the factors containing the ratio of the oil to beta
      cyclodextrin, the ratio of beta-cyclodextrin to water and the grinding time of
      the mixture of the oil, beta-cyclodextrin and water. RESULTS: The optimum
      conditions for the inclusion were as follows: the ratio of the oil to beta
      cyclodextrin was 1:10, the ratio of beta-cyclodextrin to water was 1:3, and the
      grinding time was 40 min. CONCLUSION: The optimum conditions for the inclusion
      were steady and feasible.

PMID- 20034229
TI  - [Studies on extraction process of the main saponin constituents from the stem
      bark of Kalopanax septemlobus in Guangxi].
AB  - Using orthogonal experiment design, the total saponin constituents were obtained
      by refluxing extraction with alcohol and separated by macroporous adsorption
      resin and n-Butyl alcohol from the stem bark of Kalopanax septemlobus. According
      to the purity analysis and the yield, the extraction process was optimized. The
      results showed that the main saponin constituents were gained with a yield of
      1.32% by using macroporous adsorption resin but 1.05% by using n-Butyl alcohol.
      The former was more efficient than the latter on both yield and color. The
      optimal process with isolation by macroporous adsorption resin is cheap, simple
      and practical.

PMID- 20034230
TI  - Physiology and potential application of NKT cells: a minireview.
AB  - CD1d-restricted T (NKT) cells are potent regulators of autoimmunity, tumor
      immunity, and transplantation-related immunity. NKT cells are a subset of innate
      lymphocytes that recognize endogenous or exogenous glycolipids in the context of
      CD1d molecules. Recent progress in the research of NKT cells has proved that NKT
      cells function as a bridge between innate and adaptive immunity in anticancer
      immunity. Furthermore, NKT cells also function as a bridge to tolerance or
      rejection of grafts in organ transplantation. Harnessing the function of NKT
      cells, and trying to put it into clinical application in the treatment of
      autoimmune disease, anticancer cell immunotherapy, and organ transplantation are
      the dreams of immunologists. This minireview will focus on the physiology of NKT
      cells and potential clinical application.

PMID- 20034231
TI  - Role of dopaminergic DAD1 and DAD2 receptors in the sensitization of amphetamine
      suppressed schedule-induced polydipsia in rats.
AB  - Effects of dopaminergic D1 (DAD1) and D2 (DAD2) receptors were examined in the
      sensitization of amphetamine (AMPH)-suppressed schedule-induced polydipsia (SIP).
      After training under a fixed-interval 60 sec schedule of food presentation in the
      presence of a water tube, rats received injections of different doses of AMPH 10
      min prior to the test. It was found that AMPH at 2.0 mg/kg significantly to
      reduced licks and water intake during the SIP. The AMPH-suppressed SIP manifested
      again following 5-days of pretreatment with a sub-threshold dosage of AMPH (1.0
      mg/kg) and a period of withdrawal. The role of dopaminergic D1 and D2 receptors
      was then examined by introducing D1 or D2 antagonist during the 5-days repeated
      injections of a sub-threshold dosage of AMPH. Results showed that DAD1 antagonist
      SCH23390 had little effect on the sensitization. However pretreatment with DAD2
      antagonist haloperidol (HAL) prevented the sensitization to AMPH in the long-term
      rather than short-term withdrawal conditions. It is suggested that SIP could be a
      useful paradigm to study AMPH sensitization in rats and the involvement of
      dopamine receptors might be different.

PMID- 20034233
TI  - Serum heat shock protein after simulated deep diving in Navy divers.
AB  - Deep sea diving might cause a tremendous physical or psychological stress to the
      divers. The present study aims to evaluate the stress response to a simulated wet
      dive in Navy divers. Nineteen Navy divers took part in this study when they were
      undergoing annual deep dive training. Ten divers were exposed to 190 feet of sea
      water (fsw) breathing compressed air on day 1 and to 250 fsw breathing helium
      oxygen (Heliox) gas mixture on day 3. Another 9 divers were exposed to 220 fsw on
      day 1 and 285 fsw on day 3 breathing Heliox gas mixture. The bottom time ranged
      from 5 to 8 min, and then the standard U.S. Navy air and Heliox decompression
      tables were followed for surfacing. Predive levels of serum heat shock protein 72
      (sHsp72) were 9.95 +/- 0.56 ng/ml, which were significantly higher than those in
      the control group (8.01 +/- 0.77 ng/ml). After simulating Heliox dive, the sHsp72
      increased to 10.43 +/- 0.56 ng/ml, but this was not statistically significant.
      Our results demonstrated that the serum level of Hsp72 is higher in the Navy
      divers who underwent regular intensive exercise. However, it remains unknown
      whether this increase of stress protein is associated with the diving stress or
      exercise preconditioning in the Navy divers.

PMID- 20034232
TI  - Effects of sulphur-containing compounds on plasma redox status in muscle-damaging
      exercise.
AB  - The aim of the study was to compare effects of three-day N-acetylcysteine, alpha
      lipoic acid or taurine administration on plasma antioxidant status and oxidative
      damage markers in healthy men after performing muscle-damaging exercise. Fifty
      five healthy and trained men were randomly assigned to N-acetylcysteine (NAC, 1.8
      g/day, 3 days), alpha-lipoic acid (ALA, 1.2 g/day, 3 days), taurine (TAU, 3
      g/day, 3 days) and control group (CON), and exposed to intense resistance
      exercise. The resistance exercise induced the muscle damage which was observed by
      significant increase in total creatine kinase (CK) activity at 24 h rest. The
      administration of NAC and ALA significantly elevated the resting or/and
      postexercise plasma total antioxidant status (TAS) and total thiols (TT). Uric
      acid (UA) concentration was decreased by NAC, ALA and TAU at 24 h rest compared
      with CON. The plasma lipid peroxidation (TBARS) and protein carbonylation (PC)
      were considerably reduced by NAC and ALA administration at rest and after
      exercise. TAU did not have any influence on TAS, TT, TBARS and PC levels. Our
      study has shown that three-day oral N-acetylcysteine and alpha-lipoic acid
      administration enhanced plasma total antioxidant status and attenuated oxidative
      damage whereas taurine did not demonstrate any antioxidant action in healthy men
      after performing a single muscle-damaging exercise.

PMID- 20034234
TI  - Impact of acute respiratory stress on cardiac autonomic control in young healthy
      subjects explored by time and frequency domain methods.
AB  - To find the possible utility of analysis of heart rate variability in quantifying
      transient cardiac autonomic modulation, we assessed the impact of breath holding
      induced acute respiratory stress on heart rate variability parameters and blood
      pressure in young healthy subjects. In ten healthy subjects aged between 22-24
      years of either sex, R-R intervals and blood pressure were recorded for one
      minute under resting state, during breath holding and immediately after
      withdrawal from breath holding. Heart rate variability was quantified by time and
      frequency domain methods. Mean differences in values were compared separately
      between resting and during breath holding, during and following withdrawal from
      breath holding; resting and following withdrawal from breath holding employing
      paired 't' test. Blood pressure and standard deviation of R-R intervals (SDNN)
      significantly increased during breath holding and decreased following withdrawal
      from it. Low frequency power in normalized units (LF nu) significantly decreased,
      while the high frequency power in normalized units (HF nu) significantly
      increased with a resulting decrease of the LF/HF ratio following withdrawal from
      breath holding compared to during breath holding. During the recovery phase only
      the LF% power significantly decreased as compared with the resting state. Thus,
      blood pressure and SDNN appeared to better quantify the ability of the heart to
      meet changing situational demands. LF nu and HF nu or LF/HF ratio reflected the
      behavior of sympathetic and parasympathetic limbs in adapting to changing
      situational demand.

PMID- 20034235
TI  - Protective effects of L-arginine supplementation against exhaustive exercise
      induced oxidative stress in young rat tissues.
AB  - Recently, we showed that L-arginine (L-Arg) supplementation could attenuate acute
      exercise-induced oxidative and inflammatory stress in aging rats. In this study,
      we investigate whether L-Arg supplementation protects cellular oxidative stress,
      inflammation, or the mitochondrial DNA 4834-bp large deletion (mtDNA4834
      deletion) in 14-week-old young rats tissues during exhaustive exercise. Rats were
      randomly divided into four groups: sedentary control (SC); SC with L-Arg
      treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg
      treatment (E+Arg). Rats in the SC+Arg and E+Arg groups received supplemental 2% L
      Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a
      treadmill. The results showed a significant increase in xanthine oxidase (XO) and
      myeloperoxidase (MPO) activities and lipid peroxide (malondialdehyde; MDA) levels
      of muscular, hepatic, and renal tissues in exercised rats as compared with
      sedentary rats. The increased XO, MPO, and MDA levels of these tissues
      significantly decreased in exercised rats supplemented with L-Arg. However,
      exhaustive exercise had no effect on mtDNA4834 deletions of muscular and hepatic
      tissues. The activities of creatine kinase (CK), aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine
      (CRE), lactate, uric acid, non-esterified fatty acid (NEFA), and D-3
      hydroxybutyrate in the plasma significantly increased in the exercised rats
      compared with the sedentary rats, while the CK, lactate and uric acid levels in
      the plasma significantly decreased in L-Arg-supplemented exercised rats. These
      findings suggest that L-Arg supplementation reduces the oxidative damage to and
      inflammatory response in skeletal muscles, the liver, and kidneys caused by
      exhaustive exercise in young rats.

PMID- 20034236
TI  - Attenuation of long-term Rhodiola rosea supplementation on exhaustive swimming
      evoked oxidative stress in the rat.
AB  - Rhodiola rosea improves exercise endurance and fatigue. We hypothesized that
      ingredients in Rhodiola rosea may increase antioxidant capability against
      swimming induced oxidative stress. In this study, we have identified the Rhodiola
      rosea ingredients, p-tyrosol, salidroside, rosin, rosavin and rosarin by high
      performance liquid chromatography-mass spectrometer and evaluated their O2(-)*,
      H2O2, and HOCl scavenging activities by a chemiluminescence analyzer. We next
      explored the effect and mechanism of Rhodiola rosea on 90-min swimming-induced
      oxidative stress in male Wistar rats fed with three doses of Rhodiola rosea
      extracts in drinking water (5, 25, 125 mg/day/rat) for 4 weeks. Our results
      showed that the 4 major ingredients (salidroside, rosin, rosavin and rosarin)
      from Rhodiola rosea extracts scavenged O2(-)*, H2O2, and HOCl activity in a dose
      dependent manner. The ninety-min swimming exercise increased the O2(-)*
      production in the order: liver > skeletal muscle > blood, indicating that liver
      is the most sensitive target organ. The level of plasma malonedialdehyde, a lipid
      peroxidation product, was also increased after exercise. Treatment of 4 weeks of
      Rhodiola rosea extracts significantly inhibited swimming exercise-enhanced O2(-)*
      production in the blood, liver and skeletal muscle and plasma malonedialdehyde
      concentration. The expression in Mn-superoxide dismutase Cu/Zn-superoxide
      dismutase, and catalase in livers were all enhanced after 4 weeks of Rhodiola
      rosea supplementation especially at the dose of 125 mg/day/rat. Treatment of
      Rhodiola rosea extracts for 4 weeks significantly increased swimming performance.
      In conclusion, treatment of Rhodiola rosea extracts for 4 weeks could reduce
      swimming-enhanced oxidative stress possibly via the reactive oxygen species
      scavenging capability and the enhancement of the antioxidant defense mechanisms.

PMID- 20034237
TI  - Fighting HIV, one grandmother at a time.

PMID- 20034238
TI  - HIV care in the correctional setting.

PMID- 20034239
TI  - Good things for corrections staff to know.

PMID- 20034240
TI  - The Reverend Doris Green.

PMID- 20034241
TI  - The down low vs. the lockdown.

PMID- 20034242
TI  - I smile now.

PMID- 20034243
TI  - HIV and the brain.
AB  - Right from the early years of the epidemic, researchers have recognized that HIV
      can affect the brain. Before effective antiretroviral therapy (ART), people with
      AIDS were susceptible to a variety of opportunistic infections of the brain, as
      well as HIV-related dementia. With the advent of effective combination ART in the
      mid-1990s, the prevalence of both conditions declined dramatically in areas with
      widespread access to treatment. Less severe neurocognitive impairment, however,
      remains common. In fact, some research indicates that the frequency of HIV
      related neurological impairment is rising as people with HIV live longer.

PMID- 20034244
TI  - Is HIV treatment HIV prevention?

PMID- 20034245
TI  - Transgender health and HIV.
AB  - Transgender persons illuminate the complex interplay of social and biological
      factors that determine gender identity (an individual's own sense of maleness or
      femaleness) and contribute to both HIV risk and HIV health. This article
      highlights some of the unique challenges that transgender persons face in
      maintaining their health--including avoiding HIV infection or living well with
      HIV--and discusses ways in which health-care providers can better equip
      themselves to provide care that meets the needs of transgender clients.

PMID- 20034246
TI  - God forbid...

PMID- 20034247
TI  - Colorectal liver metastasis--past, present, and the future.

PMID- 20034248
TI  - The real alternative to status quo in health plans.

PMID- 20034249
TI  - When physicians fire patients: avoiding patient "abandonment" lawsuits.
AB  - While patients have the unfettered ability to fire their physicians at any time,
      physicians can end their relationships with patients only after giving them
      reasonable notice and an opportunity to find another physician. Physicians who
      fail to take these steps may expose themselves to lawsuits for the tort of
      "patient abandonment." This article examines what circumstances may lead to a
      cause of action for the tort of"patient abandonment" under Oklahoma law. In
      addition, this article discusses the American Medical Association's (AMA)
      guidelines on terminating the physician-patient relationship and recommended
      practices by legal scholars.

PMID- 20034250
TI  - The Oklahoma experience with Double Balloon Enteroscopy: first one hundred
      procedures.
AB  - Double Balloon Enteroscopy (DBE) is a new technique that allows deep intubation
      into the small bowel, and has therapeutic capabilities including cauterization,
      biopsy, and polypectomy, as with standard endoscopes. Its major value is in the
      diagnosis and treatment of mid-gut bleeding. We report our experience with the
      first 100 DBE procedures performed in Oklahoma. The majority of our patients were
      elderly, with vasculopathy, often on antiplatelet agents. Despite this, only 1
      patient required post procedure hospitalization. Of 94 procedures performed for
      GI bleeding, positive findings were present in 55. DBE allowed treatment and or
      guided therapy in 65% of patients. Usually, DBE confirmed prior video capsule
      endoscopy. However, capsule endoscopy sometimes identified blood or pathology
      that DBE could not confirm, and, more importantly, treatable findings occurred in
      patients with prior negative capsule results. Therefore, one should strongly
      consider small bowel endoscopy in any patient with significant/or ongoing GI
      blood loss not explained by EGD or Colonoscopy.

PMID- 20034251
TI  - Primary care providers often first line of ADHD treatment.

PMID- 20034252
TI  - A view from the state Capitol.

PMID- 20034254
TI  - Hospital psychiatric interventions and its positive effect on disposition of non
      acute, long-term-care waitlisted patients: a case series.
AB  - Psychiatric interventions in hospital patients have been shown effective in
      reducing length of stay and costs. Its effectiveness and benefits in regard to
      the growing problem of disposition of non-acute, long-term-care, waitlisted
      hospital patients have not been characterized or described in the literature. The
      authors present several cases of waitlisted patients that demonstrate direct and
      indirect psychiatric interventions can play a significant role overcoming
      barriers and contributing to timely and appropriate disposition of these
      patients. Future prospective studies should be done to expand upon these findings
      to prepare for the aging of the population in Hawai'i.

PMID- 20034253
TI  - Hawai'i Island Health Workforce Assessment 2008.
AB  - BACKGROUND: Anecdotal reports of a doctor shortage on the Big Island have been
      circulating for years, but a detailed assessment of the health care workforce had
      not previously been accomplished. METHODS: The Hawai'i Island Health Workforce
      Assessment used licensure data, focus groups, telephone follow up to provider
      offices, national estimates of average provider supply and analysis of insurance
      claims data to assess the extent of the existing medical and mental health
      workforce, approximate how many additional providers might be effectively
      utilized, develop a population-based estimate of future demand and identify
      causes and potential solutions for the challenges faced. RESULTS: As of February
      2008, the researchers were able to locate 310 practicing physicians, 36 nurse
      practitioners, 6 physician assistants, 51 psychologists, 57 social workers and 42
      other mental health providers. Based on national averages, claims analysis and
      focus groups, the Island could use approximately 45 additional medical
      professionals to care for the 85% of the population that is medically insured; a
      larger number to care for the entire population. Ascertaining a complete roster
      of mental health professionals was not possible using this methodology.
      DISCUSSION: The researchers compared the current supply of physicians with the
      national average of physicians to population and the number of visits to
      different specialists for the year 2006 and found specific regional shortages of
      providers. The focus groups concentrated on solutions to the workforce crisis
      that include the formation of a well-organized, broad collaboration to coordinate
      recruitment efforts, expand and strengthen retention and renewal activities, and
      reinvigorate the health profession pipeline and training opportunities. The
      researchers recommend collaboration between the community, government, business,
      health center care providers, hospitals and centers to develop a plan before the
      tenuous state of healthcare on the Big Island worsens. In addition, continued
      surveillance of the health workforce is vital to tracking the impact of
      interventions. This could be accomplished through community informants and data
      collected at the time of professional relicensure to include practice location
      and practice intensions for future planning estimates.

PMID- 20034255
TI  - Varicella zoster virus infection in patients taking the TNF-alpha inhibitor,
      etanercept: coincidence or causal?
AB  - Ninety percent of varicella infections are seen in children under the age of ten
      and usually follow a benign clinical course with complete resolution of symptoms
      in one to three weeks. Herpes zoster an acute vesicular eruption due to the
      varicella-zoster virus (VZV), occurs mostly in adults. Biologic agents include
      tumor necrosis factor alpha (TNF-alpha) inhibitors that have significantly
      impacted the treatment of autoimmune and inflammatory conditions. Therapy with
      TNF-alpha inhibitors poses a potential risk of serious infections secondary to
      their immunomodulating properties; however multiple studies have demonstrated
      acceptable safety and tolerability profiles. A case of documented VZV infection
      (varicella) in an adult receiving the TNF-alpha inhibitor etanercept is described
      here.

PMID- 20034256
TI  - Visitor injuries in Hawai'i.
AB  - BACKGROUND: Over seven million tourists visit the Hawaiian Islands each year.
      Popular visitor activities such as surfing, scuba diving, ocean kayaking,
      parasailing, bicycle tours and hiking each have risks of serious injury. This
      study reviews visitors' activities that led to serious injuries requiring
      treatment at the state's only trauma center while vacationing in Hawai'i.
      METHODS: A retrospective electronic medical record review was conducted of all
      visitor and resident trauma patients admitted to The Queen's Medical Center (QMC)
      from January 2002-December 2006. Patient demographics, injury type and severity,
      mechanism of injury, and discharge status were collected and analyzed. RESULTS: A
      total of 8244 patients were admitted to QMC for major traumatic injuries over the
      five year study period. Of these, 466 (5.7%) were visitors. The most common
      mechanisms of visitor injuries were falls (23.6%), water-related injuries
      (22.8%), motor vehicle crashes (18.7%), motorcycle, moped, and recreational
      vehicle crashes (12.2%), assaults (7.3%), and bicycle crashes (4.0%). A
      disproportionate number of visitors sustained serious injuries while engaging in
      water-related activities: Visitors account for only 12.6% of the population on
      any given day, yet comprise 44.2% of the total admissions for Hawai'i's water
      related injuries. Head and spine injuries make up over two-thirds (68.2%) of
      these water-related visitor injuries. CONCLUSIONS: As a general category, falls
      were responsible for the highest number of visitor trauma admissions. Of the
      recreational activities leading to high numbers of trauma admissions, water
      related activities are the leading causes of serious injuries among visitors to
      Hawai'i. Water-related injury rates are significantly higher for Hawai'i's
      visitors than residents. Water safety education for visitors should be developed
      in multiple languages to educate and protect Hawai'i's visitors and visitor
      industry.

PMID- 20034257
TI  - Slippers and a white coat? (Hawai'i physician attire study).
AB  - OBJECTIVES: To ascertain patient preference regarding physician attire in
      Hawai'i, based on a sampling of patients at the Physician Center at Mililani
      (PCM), and to compare the findings with studies of patients in the continental
      United States. METHODS: Fifty patients were randomly given a questionnaire by
      front desk staff at PCM. The questionnaire asked if the participant felt it was
      acceptable for their physician to wear slippers, scrubs, short pants, blue jeans,
      and asked if they preferred their physician to wear a white medical coat. The
      second part of the questionnaire utilized a rating scale to measure levels of
      trust/confidence in their physician based on the previously noted items of
      attire. RESULTS: Patients generally approved of scrubs and blue jeans, but
      disapproved of slippers and shorts, as acceptable physician attire. By a very
      small majority patients preferred their physician NOT to wear a white coat.
      Regardless of their preferences, trust and confidence in the physician was not
      greatly affected by physician attire, according to this survey with the exception
      of the white coat--those who preferred their physician to wear a white medical
      coat bestowed a high degree of trust and confidence on this article of attire.
      CONCLUSIONS: Patients in Hawai'i, according to this small study, differ in many
      respects from their mainland counterparts. More casual forms of dress are
      generally accepted, and the white medical coat is actually NOT preferred, by a
      small majority. More extremes in casual attire, such as shorts and slippers were
      not approved as appropriate physician attire by the majority of Hawai'i patients
      in this study.

PMID- 20034258
TI  - The role of simulation at JABSOM.

PMID- 20034259
TI  - Holistic nursing: every nurse's specialty.

PMID- 20034260
TI  - Integrative cardiac care at Queen's Medical Center.

PMID- 20034261
TI  - Holistic nursing across my specialty areas of practice.

PMID- 20034262
TI  - The calling of a parish nurse.

PMID- 20034263
TI  - Aromatherapy for pregnancy and childbirth.

PMID- 20034264
TI  - Integrating massage into cancer care.

PMID- 20034265
TI  - A staff development nurse integrates holistic nursing.

PMID- 20034266
TI  - Holistic pediatric nursing.

PMID- 20034267
TI  - Holistic nursing in the community.

PMID- 20034268
TI  - Holistic nursing in mental health day treatment.

PMID- 20034269
TI  - Holism as a calling.

PMID- 20034270
TI  - My holistic practice has healed me.

PMID- 20034271
TI  - An interview with Deb Shields, 2009 Holistic Nurse of the Year.

PMID- 20034272
TI  - The vision of Ian Donald--45 years of the Queen Mother's Hospital.

PMID- 20034273
TI  - The association between drug related deaths and prior contact with hospital-based
      services.
AB  - Reducing drug related deaths has been identified as a health priority by the
      Scottish Executive. AIMS: This study investigates the association between drug
      related deaths in the Lothian region and prior contact with hospital-based
      services in the Edinburgh Royal Infirmary. DESIGN/SETTING: Retrospective analysis
      of 90 drug related deaths in Lothian from 2003-2005. Hospital episodes within
      five years of death were identified by searching the electronic patient record
      system within the Edinburgh Royal Infirmary. FINDINGS: Seventy-five of the 90
      drug related deaths occurred in the hospital catchment area. Forty five of these
      75 deaths (60%) occurred in patients who had used hospital-based services in the
      previous five years. The median time from hospital contact to deaths was five
      months and median number of hospital attendances/admissions was three (range 1 -
      26). CONCLUSION: Liaison between emergency departments, clinical toxicology
      services and community based drug addiction services is important to identify
      drug misusers at high risk. A hospital-based specialist nurse-led liaison service
      may be able to fulfil this role.

PMID- 20034274
TI  - Two novel mutations causing familial benign hypocalciuric hypercalcaemia in three
      Scottish families.
AB  - BACKGROUND AND AIMS: Familial benign hypocalciuric hypercalcaemia (FBHH) is a
      benign autosomal dominantly inherited condition which results in elevated serum
      calcium and low urinary calcium. This condition is of clinical interest because
      it can be mistakenly diagnosed as primary hyperparathyroidism (PHP). In most
      cases FBHH can be shown to be due to a mutation in the calcium sensing receptor
      (CASR) gene and we aimed to find the causative mutation in three Scottish
      kindreds with FBHH. METHODS: We used a combination of denaturing gradient gel
      electrophoresis and direct DNA sequencing to detect mutations in the CASR gene.
      RESULTS: We detected a mutation in the CASR gene in each of the three kindreds.
      Two different mutations were detected (the same one was present in two kindreds).
      Neither mutation has been reported previously. All hypercalcaemic individuals
      from each kindred had the appropriate mutation while all normocalcaemic
      individuals did not. CONCLUSION: In the vast majority of kindreds with FBHH which
      have been reported previously, the CASR mutation responsible is private to that
      kindred. In three Scottish kindreds we have identified two new mutations.

PMID- 20034275
TI  - The development and performance of a rapid-access neurovascular (TIA) assessment
      clinic in a rural hospital setting.
AB  - INTRODUCTION: Following the withdrawal of acute medical services from rural
      Angus, a rapid-access Neurovascular (TIA) Clinic was established at Stracathro
      Hospital in December 2003. Referral protocols were agreed with Angus Primary
      Care. We measured the performance of this clinic over its first two years against
      national standards outlined by Quality Improvement Scotland (2005). METHODS: In a
      retrospective study between 1st December 2003 and 30th November 2005, patient
      demographics, waiting times, investigation results, diagnoses, and secondary
      prevention issues were analysed. Challenges presented by a rural setting were
      also examined, RESULTS: By November 2005, from a total of 355 patients, 79% were
      seen within 7 days and 98% within 14 days of clinic referral. Pre-clinic bloods
      were increasingly done in general practice. All patients had CT head and carotid
      NIVA scans performed on the day of clinic attendance. A high positive diagnostic
      yield from CT scanning was obtained in the first year of the clinic, and a
      significant proportion of patients had new secondary drug prevention treatment
      recommended. Organisational and transport difficulties were addressed and
      overcome. DISCUSSION: Developing a rapid-access neurovascular clinic in a rural
      setting is achievable, and waiting times approaching national standard targets
      are possible. A TIA clinic can identify rapidly those with cerebrovascular
      disease, allowing commencement of appropriate secondary prevention therapy.

PMID- 20034276
TI  - The use of CT angiography in acute subarachnoid haemorrhage in Eastern Scotland.
AB  - INTRODUCTION: Early confirmation of aneurysmal cause for SAH can expedite patient
      management and thus minimise rebleed risk. CT Angiography is the first-line
      method for diagnosing the cause of SAH in most UK regions. We wanted to assess
      the use of CTA in this context in the East of Scotland and determine how imaging
      delays contribute to overall delay from ictus to aneurysm treatment. METHODS: A
      prospective audit of aneurysmal SAH admissions over a three month period to the
      Neurosciences Unit in Edinburgh was performed. The time from diagnosis of SAH to
      aneurysm imaging with CTA and/or DSA and time from aneurysm confirmation to
      definitive treatment was ascertained. RESULTS: Twenty nine patients with
      aneurysmal SAH were admitted during the audit. Four patients had CTA
      expeditiously after SAH was diagnosed; the remaining 25 patients had a
      substantially greater wait for aneurysm imaging, involving transfer to a
      neuroscience centre. Average excess delay was 17 hours for CTA (72 hours for
      DSA). DISCUSSION: CTA widely available and accurate method of determining the
      cause of SAH. Performing immediate CTA after SAH is confirmed could reduce delays
      to aneurysm treatment by up to 64%. By thus reducing rebleeds post SAH, immediate
      CTA could reduce poor outcomes in the East of Scotland.

PMID- 20034277
TI  - A mental health assessment and support team for community elders in Fife (EAST).
AB  - BACKGROUND: The aging population combined with the increased recognition of the
      need to assess elderly patients with mental health difficulties in their own
      environment encouraged service redesign in Fife with the focus on community
      assessment of older people with mental health needs. AIMS: To establish and
      assess the functioning of a joint Health and Social Services enhanced assessment
      and support team (EAST) for community-dwelling elders with significant mental
      health needs living in a Scottish health region, and to determine the impact of
      this team on the requirement for acute psychogeriatric hospital services.
      METHODS: Prospective three-year data collection of service activity involving
      EAST and the local psychogeriatric acute inpatient and day hospital facilities.
      RESULTS: EAST assessed 111 patients during the study, 83% with a diagnosis of
      dementia. The mean duration of assessment was six weeks with 9% of patients
      receiving an overnight home assessment and 6% requiring hospital admission.
      Overall there was a substantial reduction in utilization of both acute
      psychogeriatric admission beds and day hospital placements. CONCLUSIONS: Multi
      agency community assessment of elders with mental health problems can be
      addressed effectively without recourse to hospital admission, which may allow
      resource release for further service developments.

PMID- 20034278
TI  - Voltage-gated potassium channel-associated limbic encephalitis in the West of
      Scotland: case reports and literature review.
AB  - BACKGROUND AND AIMS: The syndrome of limbic encephalitis (LE) associated with
      antibodies against voltage-gated potassium channels (VGKC-LE) has recently been
      described. The number of published cases is however small. We therefore aimed to
      review all cases seen at our centre and compare with published cases. METHODS:
      Retrospective cases of VGKC-LE were identified using a questionnaire to
      Neurologists at the Southern General hospital, Glasgow, and by reviewing patients
      with a positive VGKC antibody test (2002-2007). Case-note review of identified
      cases and a literature review of all published cases of VGKC-LE were performed.
      RESULTS: Seven cases were identified (four female, age range 51-81). Patients
      presented sub-acutely with seizures and anterograde memory loss. Five patients
      had medial temporal lobe change on cranial imaging. No paraneoplastic cases were
      identified. 5/7 patients made some improvement with immunotherapy. In 2006, 3/18
      (17%) patients with a coded discharge of encephalitis were diagnosed with VGKC
      LE. The literature review revealed 40 patients with VGKC-LE. Age, gender or VGKC
      level did not predict likelihood for a significant recovery. Patients treated <
      or =5 months of symptom onset with immunotherapy were more likely to make a
      significant recovery (83% vs. 45%, p=0.04). CONCLUSION: VGKC-LE is being
      increasingly diagnosed and is best identified early and treated with
      immunotherapy to offer the greatest chance of recovery. This series and
      literature review expands the current published evidence in VGKC-LE.

PMID- 20034279
TI  - Indiscriminate coagulation screening of acute medical admissions: national cost
      ramifications.
AB  - BACKGROUND: Routine coagulation screening constitutes poor medical practice and
      is wasteful of resources. We aimed to determine the extent of inappropriate
      coagulopathy screening of acute medical admissions in a Scottish general
      hospital. METHODS: One hundred consecutive medical admissions were prospectively
      analysed, assessing whether or not a coagulation screen had been conducted on
      admission and whether or not this was indicated according to current hospital
      guidelines. Following targeted dissemination of guidelines to appropriate front
      door medical and nursing staff the audit was repeated. RESULTS: Pre-education,
      58% of those for whom coagulation screening was not indicated were being tested.
      After targeted education, this figure was reduced to 32%. Preeducation, 81% of
      all patients in whom coagulation screening was indicated were tested. After
      targeted education, this figure was 86%. CONCLUSION: Indiscriminate coagulation
      screening is widespread amongst medical admissions to our unit. With simple
      targeted education, we reduced the rate of inappropriate testing by 26% without
      reducing the rate of appropriate testing. In a small district general hospital
      (where the mean local cost for processing a haematology specimen is 8.59 pounds)
      this translates into a saving of 21,000 pounds per annum. Extrapolated nationwide
      this represents a cost saving of 1.15 million pounds per annum in Scotland.

PMID- 20034280
TI  - Stem cells: outstanding potential and outstanding questions.

PMID- 20034281
TI  - James Willocks and the innovation of fetal cephalometry.
AB  - James Willocks (1928-2004), a Glasgow obstetrician, was an important pioneer of
      obstetric ultrasound and the originator of the first clinically useful technique
      of fetal cephalometry. He collaborated with Tom Duggan, an engineer, who designed
      and built an electronic cephalometer to be used in conjunction with a Kelvin
      Hughes industrial flaw detector. Working in the Royal Maternity Hospital,
      Willocks was able to measure the biparietal diameter to an accuracy of better
      than 2mm. This major innovation enabled fetal growth in the third trimester to be
      accurately charted and thus greatly improved the detection of placental
      insufficiency, as well as the management of antepartum haemorrhage, hypertension
      and other complications of late pregnancy.

PMID- 20034282
TI  - Cervical cerclage in Scotland--50 years on.

PMID- 20034283
TI  - The Scottish Paediatric Society.

PMID- 20034284
TI  - Photography in dental practice--issues of consent.

PMID- 20034285
TI  - Dental records and ownership of x-rays.

PMID- 20034286
TI  - Private practice and medical aid funds.

PMID- 20034287
TI  - How long should a shortened dental arch be?
AB  - Increasing numbers of older adults are retaining teeth into old age. Many of
      these patients refuse to wear removable partial dentures, and have a high
      prevalence of dental disease and heavily restored teeth. The shortened dental
      arch (SDA) concept is a potentially cost-effective way of managing older,
      partially dentate adults. However, case selection is critical and long term
      preservation of a functional dentition may not be possible in certain patients.
      This paper highlights the critical treatment planning issues and outlines
      treatment strategies aimed at avoiding occlusal instability in patients with
      shortened dental arches. CLINICAL RELEVANCE: Appropriate application of the
      shortened dental arch concept will provide satisfactory oral function in the long
      term for partially dentate adults.

PMID- 20034288
TI  - An assessment of the relative safety of dental x-ray equipment.
AB  - Concern among patients, often prompted by medical practitioners, regarding the
      harmful effects of radiation caused by dental x-ray procedures, has caused
      several patients of the dental school of the University of Pretoria to refuse
      dental radiographic procedures. Buch and Fensham in a previous article
      demonstrated that radiation doses to the eyes and thyroid resulting from a single
      pantomogram constituted less than 10% of that which would be imparted by a
      transatlantic flight in terms of added natural background radiation. The authors
      in this study investigated doses to the same organs resulting from a full-mouth
      periapical series first using films and then digital imaging. Doses to the uterus
      resulting from these same examinations as well as from a pantomogram were also
      determined both with and without the use of a lead apron. Doses to the eye from a
      full-mouth examination using film compared favourably with those for a panoramic
      examination, but were much reduced when digital imaging techniques were employed.
      Doses to the uterus were small (equivalent to half a day of background radiation)
      for both a full-mouth examination using digital imaging, as well as for a
      pantomogram. However, from the results it would appear that there is little
      difference in the dose of scatter radiation to the uterus from a full-mouth
      examination whether or not a lead apron is used. The use of a lead apron for a
      pantomogram significantly reduces the dose to the uterus.

PMID- 20034289
TI  - Tuberculosis part 3: HIV-tuberculosis co-infection.
AB  - Tuberculosis is the most common opportunistic infection in HIV-seropositive
      persons. Tuberculosis may occur at any stage of HIV disease but the prevalence of
      TB increases with the progressive diminution of CD4+ T cell numbers. There is a
      synergistic relationship between tuberculosis and HIV infection as each
      accelerates the progression of the other.

PMID- 20034290
TI  - Beverage consumption: what and how much should we drink per day? It remains a
      question on everyone's lips--part 1.

PMID- 20034291
TI  - Oral medicine case book 21. HIV-associated Kaposi sarcoma.

PMID- 20034292
TI  - General practitioner's radiology case 77. Enamel-dentine fracture of the 21.

PMID- 20034293
TI  - Treatment planning of anterior maxilla: flap design--part 5.

PMID- 20034294
TI  - Nurses at heart of plan to save NHS over 9bn pounds a year.

PMID- 20034295
TI  - There is no middle ground regarding assisted suicide.

PMID- 20034296
TI  - Adult obesity 1: tackling the causes of the obesity epidemic and assessing
      patients.
AB  - This first in a two part unit on adult obesity examines the prevalence, causes,
      consequences and assessment of this condition. It explores the rising prevalence
      rates, offers an explanation for the increasing predisposition to obesity and
      identifies its effects on the body. Metabolic syndrome is shown to be pro
      atherogenic and a precursor to cardiovascular disease and diabetes. This part
      also outlines how to assess patients, and discusses the best way to broach the
      awkward subject of weight with those not even aware they are at risk.

PMID- 20034297
TI  - How using a patient journey approach helps to educate nurses about patient
      safety.
AB  - In its clinical update sessions for staff in children's services, a trust decided
      to use the patient journey approach to emphasise the importance of patient
      safety. The evaluation showed that this is an effective way of delivering patient
      safety messages to nurses and allied health professionals. This article explains
      the problems related to the previous didactic teaching methods and how an
      alternative interactive approach has increased staff perceptions of the
      importance of patient safety. It also demonstrates increased confidence in staff
      abilityto use the skills and knowledge gained in practice.

PMID- 20034298
TI  - Understanding the role of genetics and genomics in health 1: background.
AB  - International research efforts are resulting in a knowledge revolution which is
      constantly improving our understanding of the role of genetics and genomics in
      health and ill health. This first article in a two part series outlines the of
      this research and discusses its implications for healthcare.

PMID- 20034299
TI  - If a wound is infected with anaerobic bacteria, are there specific dressings that
      should not be used?

PMID- 20034300
TI  - Using a DVD to help people with chronic fatigue syndrome learn the technique of
      pacing.
AB  - The Shropshire Enablement Team, a specialist community rehabilitation team, has
      produced a DVD and booklet on pacing for people with chronic fatigue syndrome/ME.
      Pacing is a technique for managing fatigue, and involves achieving the correct
      balance between rest and activity. This article explains the benefits of pacing,
      and how the DVD and booklet have enabled the team to better support clients.

PMID- 20034301
TI  - Technology can back up big ideas and bold action.

PMID- 20034302
TI  - We should not see support workers as our enemy.

PMID- 20034303
TI  - [On somatotopical organization of cortical motor areas].
AB  - Early studies on cortical motor areas have been centered on their somatotopical
      organization: a reasonable direction of research from the standpoint of
      skeletomotor control of limb and body movements. On the primary motor cortex,
      anatomical and physiological studies revealed aspects of somatotopical
      organization in progressively finer scales. Earlier studies were directed at
      elucidating the fine-grain modular organization of the primary motor cortex.
      Later studies, however, emphasized the diversity of output organization in
      individual part of the cortex, even at a single-cell level. At present, there is
      no convincing evidence for the existence of microstructures representing any form
      of unitary function. As for nonprimary motor areas, the existence of
      somatotopical organization has been inferred based on anatomical studies and on
      studies utilizing microstimulation. In the supplementary motor area, the body
      part representation is broadly organized rostrocaudally in the order of face,
      forelimb and hindlimb areas, although with an extensive overlap of each area. In
      contrast, somatotopy is not apparent in the presupplemenetary motor area;
      effector-independent control of motor behavior seems to be dominant in this area.
      In the premotor cortex, motor acts involving the hindlimb appears to be much less
      represented than actions involving hand-arm and face. Overall, in considering the
      workings of nonprimary areas, aspects of motor behavior involving sensorial
      guidance, action-selection, or visuomotor association appear to be of primary
      importance rather than the determination of body parts to be used.

PMID- 20034304
TI  - [Somatotopy and information processing in the somatosensory cortex].
AB  - The present article reviews studies on the somatotopic representation of the body
      in the postcentral gyrus. The review consists of 3 sections namely the early
      studies on the cortical localization of somatosensory in humans and animals,
      earlier neurophysiological studies in monkeys by recording single units, and more
      recent studies in human subjects. Results of the neurophysiological studies in
      monkeys established a hierarchical scheme of information processing and have
      guided the latest studies on human subjects that use various modern techniques
      such as neuroimaging. This review illustrates the origin of the concept of
      somatotopic representation of the body, its utilization in the later cortical
      mapping studies, and what is the reality of the concept.

PMID- 20034305
TI  - [Somatotopy in the basal ganglia].
AB  - Somatotopy is a fundamental concept that is essential for the understanding of
      the functions of the brain. Here, I have described somatotopy in the basal
      ganglia that comprise the striatum, subthalamic nucleus, globus pallidus, and
      substantia nigra. Projections from the motor cortical subregions that represent
      different body parts terminate in different regions of these nuclei. Basal
      ganglia neurons respond not only to the stimulation of the corresponding
      subregions of the motor cortices but also to the active and passive movements of
      the corresponding body parts. On the basis of these anatomical and physiological
      findings, somatotopy can be identified in the motor territories of these nuclei
      in the basal ganglia. In addition, projections from functionally interrelated
      cortical areas partially converge through a cortico-basal ganglia loop.
      Disorganized somatotopy may explain, at least in part, the pathophysiology of
      movement disorders such as Parkinson disease and dystonia.

PMID- 20034306
TI  - [Somatotopy in the emotional expression by the amygdala].
AB  - Sensory information of various modalities is integrated in the amygdala, where
      the emotional information is subsequently generated. The resultant emotional
      information is then sent to the widespread cortical and subcortical areas. This
      output to the cortex is directed to the prefrontal cortex and the medial temporal
      lobe, a memory system, and modulates the higher cortical functions as well as the
      learning and memory. The output to the subcortical structures is directed to the
      hypothalamus and brainstem, and the autonomic, hormonal and behavioral responses
      are elicited as the expression of the emotional response. Taking into account the
      above mentioned emotional system, the examination of somatotopic representation
      in the amygdala and related structures is very difficult. However, recent studies
      have elucidated the somatotopic representation of the amygdalar output system in
      the brain of rhesus monkey. The lateral basal nucleus of the monkey amygdala was
      proved to project to the cingulate motor cortex M3, and the target cortical
      neurons project somatotopically to the facial nucleus in the brain stem.
      Accordingly, the amygdala-cingulate cortex-facial nucleus system is involved in
      the emotional expression by the facial movement. This system might be involved in
      the pathophysiology of temporal lobe epilepsy and the facial expression of
      patients with Parkinson disease. Furthermore, the amygdala-cingulate cortex
      projection develops from adolescence to adulthood and reflects the emotional
      maturation and the development of social adaptation.

PMID- 20034307
TI  - [Reconsidering somatotopy with respect to functional recovery from spinal cord
      injury].
AB  - Somatotopy, which is the representation of various body parts on the topographic
      map in the sensory and motor cortices, is one of the most well-known concepts in
      neuroscience. However, defining motor cortex areas, for instance, the hand
      region, the terms of somatotopic organization is a complex process. The "hand
      region" can be defined either by (i) low-threshold induction of twitch in hand
      muscles on repetitive microstimulation, (ii) detection of sensory inputs from the
      hand, (iii) presence of cortico-motoneuronal (CM) cells that communicate directly
      with the motoneurons of hand muscles, or (iv) presence of neurons that exhibit
      increase in firing activity before the onset of hand movements. The relationship
      between these criteria is not clear. Further the somatotopic map is known changes
      in response to environmental conditions and lesions of the central nervous
      system. However, the nature of changes depends on the manner in which a given
      region is defined. To define cortical regions on the basis of somatotopic
      organization, it is essential to carefully inspect the stimulus threshold for
      induction of movements and correlate the obtained response and the presence of CM
      cells. It is also necessary to identity the communicating pathways between the CM
      cells of a given region and the respective motoneurons. It will lead to
      understanding the relation between the structural change in the somatotopic
      representation map and its functional roles in the motor control.

PMID- 20034308
TI  - [Factors behind action, emotion, and decision making].
AB  - Human actions, emotions, and decision making are products of complex interactions
      between explicit and implicit processes at various levels of spatial and temporal
      scales. Although it may not be possible to obtain to experimental data for all
      the complexity of human behavioral and emotional processes in our everyday life,
      recent studies have investigated the effects of social contexts on actions,
      emotions, and decision making; these studies include those in the fields of
      experimental psychology, cognitive science, and neuroscience. In this paper, we
      review several empirical studies that exemplify how our actions, social emotions,
      and decision making are influenced by the presence of implicit external, rather
      than internal factors, particularly by presence of other individuals. The
      following are the main principles identified. (1) Unconscious behavioral
      contagion: Individuals tend to mimic others' actions. This tendency occurs
      unconsciously even when the observed and the to-be-executed movements are
      unrelated at various levels and aspects of behaviors (e. g., behavioral tempo and
      speed). (2) Neural substrates of social emotions: Various social emotions,
      including admiration, compassion, envy, and schadenfreude, are represented in
      neuronal networks that are similar to those of basic emotional processes. (3)
      Evasive nature of human decision making: Individuals tend to overrate their own
      subjective impression of and emotional reaction in forecasting affective reaction
      to events in the future, even though the predictive power of information from
      peer group is much larger in this regard. Individuals are seldom aware of the
      dissociation between their intended choice and excuted actions and are willing to
      give elaborate explanations for the choices they, in fact, did not make. Using
      these empirical examples, I will illustrate the considerable influences of
      implicit, unconscious processes on human actions, emotions, and decision making.

PMID- 20034309
TI  - [Increased urinary sodium excretion in the early phase of aneurysmal subarachnoid
      hemorrhage as a predictor of cerebral salt wasting syndrome].
AB  - Cerebral salt wasting syndrome (CSWS) in patients with aneurysmal subarachnoid
      hemorrhage (SAH) is considered to correlate with delayed ischemic neurological
      deficits (DIND) induced by cerebral vasospasm; however, its exact mechanism is
      still not well-known. The purpose of the present study is to evaluate the
      relationship between hyponatremia caused by CSWS and the increase of the urinary
      sodium excretion in early phase following SAH. Fifty-four patients with SAH were
      divided into 2 groups, normonatremia group and hyponatremia group which suffered
      hyponatremia after SAH. The hyponatremia group comprise 14 patients (26%) in whom
      the hyponatremia developed of the SAH. In this group, the serum level of sodium
      significantly decreased 7 days after SAH and then gradually normalised. Further,
      excretion of sodium in the urine tended to increase 3 days after SAH and
      significantly increased 7 days after SAH. In conclusion, the increased urinary
      sodium excretion in the early phase of SAH would serve as a predictive factor for
      CSWS after SAH. We consider that it is important to start sodium and fluid
      supplementation and inhibit natriuresis by fludrocortisone acetate administration
      before hyponatremia occurs in order to prevention delayed ischemic neurological
      deficits in SAH patients.

PMID- 20034310
TI  - [Unusual distribution of blood in a ruptured aneurysm--case report].
AB  - Computed tomography (CT) is an important tool for the evaluation of subarachnoid
      hemorrhages caused by ruptured aneurysms. However, an unusual radiologic
      presentation of blood can result in the misdiagnosis of the rupture site. We
      report a case of ruptured right internal carotid-posterior communicating (IC-PC)
      artery aneurysm with an unusual radiologic presentation of hemorrhage. The CT
      scans images of this patient were indicative of blood clots in the cisterna magna
      and the ventricles with no blood collection in the suprasellar cistern or sylvian
      fissure. The intraventricular clots were mainly distributed in the fourth
      ventricle, with few clots in the lateral ventricles. On the basis of these
      findings, we suspected the origin of the hemorrhage was an unknown ruptured
      posterior fossa aneurysm. However, angiography revealed a right internal carotid
      posterior communicating (IC-PC) artery aneurysm. Twenty-three days after onset, a
      repeat CT confirmed that the origin of the hemorrhage was the right IC-PC
      aneurysm. Possible factors involved in this case were: (1) formation of adhesions
      in the subarachnoid cisterns due to an earlier minor leakage, (2) the orientation
      of the aneurysm (posteroinferior direction), and (3) early wash out of the blood
      clot.

PMID- 20034311
TI  - [Three cases of cervical epidural hematoma mimicking acute ischemic stroke].
AB  - We report 3 cases of spontaneous cervical epidural hematoma with sudden onset of
      neck pain followed by the development of unilateral limb weakness. All of the
      patients were initially suspected to have acute ischemic stroke. We considered
      using intravenous thrombolysis with recombinant tissue plasminogen activator (rt
      PA) to treat 2 of the 3 patients who had arrived at our hospital within 2 hours
      of the symptom onset. However, we did not administer rt-PA therapy to these
      patients because the symptoms were mild. We treated all 3 patients with other
      antithrombotic drugs until the diagnosis of cervical epidural hematoma was
      confirmed. Patients with spontaneous cervical epidural hematoma usually present
      with acute neck pain followed by the development of bilateral limb weakness and
      urine retention; unilateral limb weakness is rare. Patients with this uncommon
      presentation must be distinguished from stroke.

PMID- 20034312
TI  - [One hundred books which built up neurology (36)--Cruveilhier "Medecine Pratique"
      (1821), "Traite D'Anatomie Descriptive" (1851)].

PMID- 20034313
TI  - Effects of ulnar deviation of the wrist combined with flexion/extension on the
      maximum voluntary contraction of grip.
AB  - Work-related musculoskeletal disorders (WMSDs) is related with the frequency of
      exertion for repetitive tasks requiring heavy load. Different researchers have
      reported that a poor posture is very much responsible for WMSD if combined with
      increased load and/or frequency. In the assembly tasks in different industries
      involve the gripping very commonly. Therefore in the present study it was tried
      to find the effect of a wrist posture on grip strength. For design of experiment,
      subjects, flexion/extension and ulnar deviation of the wrist were taken as
      independent variables and the dependent variable was maximum voluntary
      contraction (MVC) of grip. The results showed that the effect of
      flexion/extension angle, ulnar angle and the subject on MVC grip were highly
      significant (i.e., p<0.001, 0.001 and 0.002 respectively). The two-way
      interaction effect of flexion/extension angle of the wrist and the subject on MVC
      grip was also found significant at p<0.001. The other interaction effects were
      not found significant. MVC grip was found maximum at the neutral wrist posture.

PMID- 20034314
TI  - Effect of passenger position on fear of danger experienced during sudden bus
      stops.
AB  - The purpose of this study was to identify the effect of bus passengers' positions
      on their fear of danger when a bus stopped suddenly. A temporary bus running
      course with one bus stop was set up on the campus of the Tokyo University of
      Agriculture and Technology (TUAT). The bus ran the course 14 times with the bus
      stopping twice during the course, once at the bus stop and again just after re
      starting from the bus stop. The driver was asked to brake more strongly than
      usual when stopping. Sixteen students (15 males and 1 female) between the ages of
      18 and 21 years participated. In turn, all participants were asked to take 14
      different postures in the bus. Participants were also asked to report their level
      of fear on a rating scale each time the bus stopped. The study showed that (1)
      passengers' fear of danger at the first sudden stop was typically higher than
      that at the second stop, (2) standing passengers who held hand straps experienced
      more fear than those who held fixed safety devices, (3) bus passengers sitting on
      the centre of the rear seat had a great risk of injury if the bus stopped
      suddenly, and (4) when passengers faced the window and stood transversely with
      respect to from the moving direction of the bus and the bus stopped suddenly,
      passengers' fear of danger was affected by the side of the bus on which they
      stood as well as which hand they used to grasp a safety device.

PMID- 20034315
TI  - How the number of years of sports experience and the frequency of sports
      activities can influence the quality of life of people with challenges.
AB  - The present study focused on the users of sports centres for people with
      challenges to identify the relationship between sports activities and quality of
      life (QOL) of the users. A centre established in H Prefecture in 1996 (Centre H)
      and another in T Prefecture in 2006 (Centre T) were studied to find out how
      differences in the number of years of sports experience and frequency of sports
      activities could affect QOL scores of the 36-Item Medical Outcomes Study Short
      Form Health Survey (SF-36). The examination of the relationship between the
      number of years of sports experience and the total QOL scores of the respondents
      at both centres revealed significantly better QOL scores on the bodily pain (BP)
      and role emotional (RE) scales among the respondents with three or more years of
      sports experience, compared to those with less than three years of sports
      experience. On the whole, the higher the number of years of sports experience and
      the greater the frequency of sports activities, the better the QOL scores were.
      These results suggest that sports activities contribute greatly to the
      improvement of the everyday QOL of challenged individuals and long years of
      frequent sports activities have a beneficial impact on the QOL of physically
      challenged individuals.

PMID- 20034316
TI  - A study of anthropometric characteristics between Malaysian and Saudi Arabian
      males aged 20 to 30 years.
AB  - This study presents a comparison of the anthropometric characteristics of 241
      Malaysian and 646 Saudi Arabian males aged 20 to 30 years. The mean values,
      standard deviation (SD), and 5th and 95th percentile values of 26 measurements
      and 22 proportions of each group were given. The results showed that there were
      significant differences in a number of body dimensions between these populations,
      except for eye height and elbow height (standing) and height, eye height,
      shoulder height, and elbow height (sitting). These results are important for the
      ergonomic design of workstations, personal protective equipment, tools, interface
      systems and furniture: The presented data may be useful for providing a safer,
      more productive and user-friendly workplace for Malaysian and Saudi Arabian
      populations.

PMID- 20034317
TI  - [Purpura fulminans (symmetric peripheral gangrene): 7-year consecutive case
      review in Japan].
AB  - BACKGROUND: Acute infectious purpura fulminans (AIPF), a rare syndrome of
      infection-induced ischemic necrosis of the extremities (symmetric peripheral
      gangrene), is due most often to Neisseria meningitidis in the US and the UK, but
      is not endemic to Japan. PURPOSE: We reviewed clinical AIPF manifestations in
      Japan. METHODS: (A) We retrospectively analyzed six cases of AIPF in the last
      seven years. (B) We reviewed the medical literature up to 2008 using PubMed
      search and Japana Centra Revuo Medicina (Igakuchuozasshi) findings. RESULTS: (A)
      None of the 6 subjects-5 men and 1 woman aged 44 to 69 old- had a history of
      splenectomy. Except for one case, their disease was community-acquired and
      immunocompetent. Causative organisms were Streptococcus pneuomoniae (66.7%), Gram
      negative rods, and Legionella pneumophilla. No localized infectious focus was
      apparent except for one of Legionella pneumonia. Systemic purpura progressed
      rapidly within 12 to 96 hours of initial fever or influenza-like symptoms. Main
      AIPF manifestations are shock and disseminated intervascular coagulation, but not
      all subjects had both. Six-month mortality was 33.3%, with death within two days
      of admission. Survivors all required at least two limbs to be amputated. (B) The
      Japanese literature reported AIPF occurring in 64 cases- 11 neonatal due to
      congenital protein C deficiency, seven pediatric, and 46 adults. Organisms most
      commonly involved were S. pneumoniae at 41.3%, and Neisseria meningitidis at
      15.2%. The most common pathogen reported in a PubMed search was Neisseria
      meningitidis. CONCLUSIONS: In Japan, S. pneumoniae is the most frequent isolate
      associated with AIPF, and progression to AIPF occurs mainly in adults, who
      commonly suffer frequent amputations and high mortality. Rapid progressing
      systemic purpura following common-cold-like symptoms is the key to early
      diagnosis, even if the patient is immunocompetent, not splenectomized, or has no
      apparent infectious foci.

PMID- 20034318
TI  - [A study of group A Streptococcus strains isolated from children with recurrent
      group A streptococcal infection].
AB  - Recurrent Group A Streptococcus (GAS) infection was defined as a case in which
      GAS infection was suspected during June 2006-December 2008 and GAS was detected
      more than 2 times by throat culture. T serotype and emn genotype were
      investigated for GAS bacteria isolated from children with recurrent GAS
      infection. Bacteria gene homology was studied using pulsed-field gel
      electrophoresis (PFGE). Of the 43 cases of GAS infection in 21 children used as
      subjects, 20 had GAS infection 2 times and one 3 times. A comparison of the first
      and second infection in subjects (and the second and third for the child with 3),
      bacteria isolated from 11 cases had coincident properties and those from the
      remaining 11 not-coincident. The mean period of first and second infections
      (second and third for the child with 3) was 29.1 +/- 17.1 days for the coincident
      group and 215.2 +/- 187.8 days for the not-coincident group. A significant group
      difference in period was seen (p = 0.0013). Ten of 12 children with recurrent GAS
      infection within 8 weeks of the first infection and one of 10 who had it more
      than 8 weeks after that were included in the coincident group, indicating a
      significant difference (p = 0.0028).

PMID- 20034319
TI  - [Clinical study of iliopsoas abscess in 11 cases from 2005 to 2008].
AB  - Iliopsoas abscess, a rare disease, has shown a recent alarming increase in the
      number of patients, especially among older people. This clinical study of
      iliopsoas abscess in 11 cases seen from 2005 to 2008, showed the average age of
      patients to be 76 years-higher than the average. Causes were often orthopedic
      diseases such as pyogenic spondylitis. The four most commonly recognized
      underlying diseases were spinal, including lumbar spinal canal stenosis and
      lumbar disc herniation. Antibiotic induced a cure in only 6 of 11 cases. In this
      conservatively treated group, average abscess diameter was significantly smaller
      than in the non conservatively treated group. Conservative treatment thus
      requires that such abscess be detected as early as possible.

PMID- 20034320
TI  - [A case of Reye's-like syndrome due to suspected Bordetella pertussis infection
      in an adult].
AB  - We report a rare case of Reye's-like syndrome associated with suspected pertussis
      infection. A 26-year-old woman admitted comatose and found in laboratory studies
      to have acute liver dysfunction, severe hypoglycemia and prolonged prothrombin
      time, was diagnosed with clinical Reye's-like syndrome due to aspirin use. Her
      child was probably infected with pertussis, which she contracted and which, in
      turn, triggered Reye's-like syndrome.

PMID- 20034321
TI  - [An autopsy case involving severe sepsis due to Capnocytophaga canimorsus
      infection].
AB  - Capnocytophaga canimorsus, a commensal bacterium from the carine mouth, causes
      septicemia in human beings through bites or scratches. We report a case of a 60
      year-old man contracting septicemia due to C. canimorsus infection after a dog
      bite who died less than 12 hours after admission. We observed neutrophils with
      intracytoplasmic bacilli in the peripheral blood smear. We discuss clinical
      presentation and autopsy findings.

PMID- 20034322
TI  - [A case of empyema in a previously healthy child caused by Streptococcus
      pneumoniae serotype 1].
AB  - A 6-year-old boy admitted for empyema was found to have Streptococcus pneumoniae
      serotype 1 isolated from both blood and drainage fluid. The organism had no
      mutated genes encoding penicillin-binding proteins and was susceptible to all
      antibiotics. Empyema caused by S. pneumoniae serotype 1 in childhood has not, to
      our knowledge, been reported in Japan. In many countries where nanovalent
      pneumococcal conjugate vaccine (PCV7) has been introduced, serotype 1 frequency
      is especially high and empyema prevalence has increased. Monitoring of this S.
      pneumoniae serotype may be more important in invasive pneumococcal disease (IPD)
      than previously thought, especially in empyema, even after PCV7 is introduced in
      Japan.

PMID- 20034323
TI  - [A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia
      developing ecthyma gangrenosum while undergoing combined imatinib mesylate
      chemotherapy].
AB  - A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype
      leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to
      periorbital edema while undergoing combined imatinib mesylate (imatinib)
      chemotherapy. Although initial periorbital edema was considered an imatinib side
      effect, the lesion deteriorated rapidly with high fever in the neutropenic phase,
      and the woman died of septic shock. Cultures from blood and exudative fluid grew
      Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized
      emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa
      bactremia. Because some patients present with EG a few days prior to developing
      life-threatening septicemia, it is important that EG be diagnosed correctly.
      Imatinib side effects such as edema are usually tolerable, and imatinib is widely
      used to treat Philadelphia-chromosome-positive leukemia, particularly in those
      with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib
      therapy are expected to increase in number. Delay in initiating appropriate
      therapy is correlated with poor outcome, so drug side effects and EG must be
      carefully differentiated when skin edema with surrounding erythema is noted in
      neutropenic patients undergoing imatinib therapy.

PMID- 20034324
TI  - [Real-time PCR in rapid diagnosis of Aeromonas hydrophila necrotizing soft tissue
      infections].
AB  - We report a case of rapidly progressive necrotizing soft tissue infection and
      sepsis followed by a patient's death. We suspected Vibrio vulnificus infection
      because the patient's underlying disease was cirrhosis and the course extremely
      rapid. No microbe had been detected at death. We extracted DNA from a blood
      culture bottle. SYBR green I real-time PCR was conducted but could not detect V.
      vulnificus vvh in the DNA sample. Aeromonas hydrophila was cultured and
      identified in blood and necrotized tissue samples. Real-time PCR was conducted to
      detect A. hydrophila ahh1, AHCYTOEN and aerA in the DNA sample extracted from the
      blood culture bottle and an isolated necrotized tissue strain, but only ahh1 was
      positive. High-mortality in necrotizing soft tissue infections makes it is
      crucial to quickly detect V. vulnificus and A. hydrophila. We found real-time PCR
      for vvh, ahh1, AHCYTOEN, and aerA useful in detecting V. vulnificus and A.
      hydrophila in necrotizing soft tissue infections.

PMID- 20034325
TI  - [Two severe tetanus cases infected in an urban area of Kawasaki City].
AB  - We report two cases of severe tetanus infection. Case 1: A 73-year-old non
      vaccinated man who fell in a local park developed a wound on the left little
      finger. The wound was debrided and a tetanus toxin shot given on day 4 following
      the injury. He developed trismus on day 6 requiring deep sedation and mechanical
      ventilation in the intensive care unit (ICU), with human anti-tetanus immune
      globulin (TIG) and antibiotics administered. Despite a very severe autonomic
      dysfunction, he recovered and was discharged mobile after 2 months of
      rehabilitation. Case 2: A 37-year-old woman fully vaccinated against tetanus in
      her childhood had apparently had booster vaccine for at least 20 years and was
      being treated for hyperthyroidism with thiamazole. She sustained two lacerations
      on the fingers of her right hand in her backyard. She noticed difficulty in
      opening her mouth on day 3 following the injury and was seen on day 7, for high
      fever and difficulty in speaking. She was diagnosed clinically as having tetanus
      and underwent wound debridement, and a shot of tetanus toxin, TIG, and
      antibiotics. On hospital admission day 2, she developed spasms and her blood
      pressure dropped drastically. She died the next day due to endotoxin shock caused
      by other bacteria. C. tetani is widely distributed in Japan, and these cases
      underscore the importance of maintaining adequate tetanus antibody levels through
      booster administration every 10 years in immune adults and appropriate post
      exposure treatment with tetanus toxin and/or prophylactic TIG administration.

PMID- 20034326
TI  - [Clostridium difficile-associated diarrhea due to antimicrobial for perioperative
      antibacterial prophylaxis-clinical observation in 8 patients].

PMID- 20034327
TI  - [Post-encephalitic syndrome in patients with tick-borne encephalitis].
AB  - BACKGROUND: It was 55 years ago when the first patients with tick-borne
      encephalitis (TBE) were diagnosed in the Koprivnica-Krizevci County. Since then,
      we have acquired some new knowledge about the disease. TBE is an endemic disease
      and the second most common tick-borne disease following Lyme borreliosis in our
      country, with an average morbidity rate of 12 patients per year and predominance
      of male individuals older than 50. There are no specific risk groups because such
      patients have been continuously vaccinated for the past 27 years. In 88.0% of
      patients, the infection is manifested as aseptic meningitis and
      meningoencephalitis with a biphasic course. As opposed to detailed descriptions
      of acute morbidity, there are few reports on the course of disease and its
      outcome. OBJECTIVES: The aim of the study was to assess the presence of post
      encephalitic syndrome (PES) in patients with TBE, to evaluate its incidence and
      demonstrate its characteristics. PATIENTS AND METHODS: This prospective study was
      conducted from 1995 to 2008 and enrolled PES patients treated at Department of
      Infectious Diseases, Dr. Tomislav Bardek General Hospital in Koprivnica during
      the study period. The study included patients of both sexes older than 14 years
      with recent TBE virus infection, patients with clear temporal correlation between
      acute morbidity and PES onset, and patients where any other cause of PES was
      ruled out. The immunoenzyme linked assay (ELISA) was used for detection of serum
      IgM and IgG antibodies. Recent TBE virus infection was detected in 133 patients.
      Nine of these patients refused further cooperation, and the remaining 124
      patients, 80 male (64.5%) and 44 female (35.4%), aged 16-76, were included in the
      study. We longitudinally examined the manifestation and characteristics of PES in
      each patient during a 3-year period (and longer if necessary). Study patients
      were divided into three groups of mild, moderate and severe PES based on data
      collected and entered into specially prepared questionnaire and by qualitative
      analysis of PES effect on their daily habits and activities. RESULTS: Out of 124
      patients included in the study, 60 (48.3%) had no symptoms/signs of PES, or these
      were mild and of short duration 15 (12.0%). The remaining 49 (39.5%) patients
      developed moderate (30/47.0%) or severe (19/30.0%) PES lasting for 3-18 months,
      with significant impact on their daily habits and activities requiring some
      adjustment. The main characteristics of PES were mental disorders, balance and
      movement coordination disorders, headache, general malaise, and reduced working
      ability. PES was recorded in 35 (28.2%) patients with meningoencephalitis and 14
      (11.2%) patients with meningoencephalomyelitis. Permanent sequels were left over
      in 11 (17.1%) patients: spinal nerve paresis in five (4.0%), hearing impairment
      in six (5.6%), dysarthria in two (1.6%) patients, and severe mental disorder in
      one (0.8%) patient. In three patients we recorded simultaneous permanent spinal
      nerve paralysis and permanent deafness. During our longitudinal study three
      (2.5%) patients died. CONCLUSION: The study undoubtedly confirmed the presence of
      PES in our patients with TBE. Moderate and severe PES has a significant impact on
      the patient quality of life, demands patient adjustment, and increases expenses
      of long-term sick-leave and rehabilitation.

PMID- 20034328
TI  - [Therapeutic response in outpatient opioid substitution treatment].
AB  - AIM: The aim of the study was to compare the success of buprenorphine therapy
      induction between two groups of outpatients. SUBJECTS AND METHODS: The analysis
      was retrospective, based on medical documentation from the Centre for Prevention
      of Drug Addiction, Public Health Institute of the Split-Dalmatia County, Split,
      Croatia. The success of buprenorphine treatment induction and maintenance was
      compared between two groups of outpatients treated in 2006 (group 1, n=24) and
      2007 (group 2, n=28), observed for the first four months of both years and only
      patients that presented to the Centre once a week for at least one month were
      included. The dose of buprenorphine was 2-4 mg per day in group 1 and 6-8 mg per
      day in group 2. Between group differences were compared using chi2-test with
      Yates correction and Mann-Whitney U-test. The probability value of P<0.05 was
      considered significant. RESULTS: There was no significant difference between
      groups in demographic characteristics (sex, age, employment, education and
      marital status) and duration of heroin use. In group 1, 12 (50%) patients
      continued buprenorphine substitution treatment after 30 days, whereas in group 2
      this figure was 21 (75%) patients (P<0.05). A significant difference between
      groups was also recorded in positive urine opiate test in the first and second
      week (P<0.05). CONCLUSION: Pharmacotherapy alone is rarely sufficient treatment
      for drug addiction, but it is an essential part of opioid substitution treatment.
      Therefore it is important to recommend an adequate dose of agonist or
      agonist/antagonist medication. As the cost of buprenorphine therapy has been
      reimbursed by the Croatian Health Insurance Institute in full amount since the
      beginning of 2007, a higher ("adequate") dose of buprenorphine is recommended to
      improve the success of buprenorphine treatment induction and maintenance.

PMID- 20034329
TI  - [The review of carbapenem resistance in clinical isolates of Acinetobacter
      baumannii].
AB  - Increasing reports of Acinetobacter infections that cause pneumonia, meningitis,
      endocarditis, and bacteriaemia underline the clinical importance of this
      pathogen. Members of the genus Acinetobacter, particularly Acinetobacter
      baumannii, are now recognized as significant nosocomial pathogens, particularly
      for the subset of critically-ill patients requiring mechanical ventilation in
      hospital intensive care units. A. baumannii has itself a quite high level of
      naturally-occurring antibiotic resistance. The organism can survive for long
      periods in the hospital environment including dry and humid areas. One of the
      most worrying antibiotic resistance problems in A. baumannii is the increasing
      trend of carbapenem resistance, present also in few Croatian hospitals.
      Infections caused by this Gram-negative bacillus are common in the intensive care
      units anticipated by colonized patients. The increasing trend of carbapenem
      resistance in A. baumannii could be mediated from metallo-beta-lactamases (VIM,
      IMP, and SIM), carbapenem-hydrolyzing oxacillinases (OXA), porin modifications
      for influx of carbapenems (33-kDa CarO protein) and/or often combined mechanisms
      of resistance. The investigation of the background of carbapenem resistance in
      relevant clinical isolates of A. baumannii from Split University Hospital
      confirmed present of carbapenem-hydrolyzing oxacillinases OXA-107 representing a
      more recent evolutionary adaptation OXA-51-like enzyme to antibiotic challenge
      with carbapenems.

PMID- 20034331
TI  - [The role of zinc in the treatment of hyperactivity disorder in children].
AB  - Zinc is an essential cofactor of more than 100 enzymes, including metalloenzymes
      and metalloenzyme complexes, which are necessary in the metabolism of
      carbohydrates, fatty acids, proteins and nucleic acids. It is an important factor
      in the metabolism of neurotransmitters, prostaglandins, and for maintaining brain
      structure and function. Dopamine is one of the most important factors in the
      pathophysiology of hyperactivity disorder, and the hormone melatonin has an
      important role in the regulation of dopamine. Because zinc is necessary in the
      metabolism of melatonin, it can be assumed that zinc is a very important factor
      in the treatment of attention deficit and hyperactivity disorder (ADHD). It is
      known that deficit of some minerals and vitamins is connected with hyperkinetic
      disorder. Preliminary investigations in humans show that many children with ADHD
      have lower zinc concentration in relation to healthy children. Zinc sulfate as an
      adjunct to methylphenidate has favorable effects in the treatment of ADHD
      children, pointing to the possible association of zinc deficit and ADHD
      pathophysiology. Zinc concentration can only point to some other factors
      (malnutrition) that can lead to ADHD, but is not a factor that has a causative
      role in ADHD. Therefore, zinc supplementation to nutrition or to ADHD therapy may
      be of great benefit in ADHD children with zinc deficit or low plasma zinc
      concentration. ADHD occurs in different cultures, mostly before seven years of
      age. In children younger than five years it is difficult to make an accurate
      diagnosis because their behavior is more variable than in older children.
      Hyperactive disorder is mostly observed in younger age, i.e. in childhood and
      adolescence. The majority of the main characteristics are less pronounced or
      completely lost in adult age. In the 1960s, the disorder was named "minimal
      cerebral dysfunction" and was most often the consequence of head trauma or low
      birth weight. Later, the term was changed as hyperactive reaction in childhood.
      Recent studies estimate its prevalence to three of ten hyperactive children, and
      there are data that about 4% of children have the complete frame of the disorder.
      The condition is more common in boys than in girls. The reason probably lies in
      the fact that girls primarily develop attention disorder and cognitive problems
      (concentration, memory, thinking), and less often have symptoms of aggressive and
      impulsive behavior, thus boys being earlier referred for examination. There are
      many theories about the possible origin of hyperactive disorder, and one of the
      most widely studied is the theory of the role of dopamine, which is supported by
      the results of treatment in these children with dopamine agonists like
      methylphenidate and amphetamines. Recent studies do not neglect the influence of
      maternal intake of food and drink additives, alcohol consumption and smoking
      during pregnancy, soil contamination, and low birth weight. Zinc is a coenzyme of
      the enzyme delta-6 desaturase, which is important in the anabolism of
      polyunsaturated long chain fatty acids, linolic and linolenic acids that
      constitute neuronal membrane. Studies point to the possible association of zinc
      deficiency and ADHD pathophysiology. In ADHD children with zinc deficiency or low
      plasma zinc concentration, zinc dietary supplementation or during therapy for
      ADHD may be of great benefit. A study of ADHD treatment with zinc sulfate as a
      supplement to methylphenidate showed beneficial effects of zinc supplementation
      in the treatment of children with ADHD. The dose of zinc sulfate used was 55
      mg/day, which is equivalent to 15 mg zinc. The improvement achieved in ADHD
      children with the use of zinc sulfate appears to confirm the role of zinc
      deficiency in the etiopathogenesis of ADHD. Additional studies are needed to
      identify the real and efficient dose of zinc.

PMID- 20034330
TI  - [Thrombophilia, preeclampsia and other pregnancy complications].
AB  - The aim of this paper is to present the latest developments in therapy and
      prophylaxis of deep vein thrombosis and other pregnancy complications in women
      with inherited or acquired thrombophilia and in women with mechanical heart
      valves. The data presented in the paper have been extracted from the Current
      Contents database. It is well known that the hypercoagulable state in pregnant
      women, caused either by the physiological changes of pregnancy or by inherited
      thrombophilia, increases the risk of venous thromboembolism (VTE), pulmonary
      embolism (PE), preeclampsia, recurrent early and late fetal loss, intrauterine
      growth retardation (IUGR), placental abruption, and other less probable
      complications of pregnancy and its outcome. In women with mechanical heart
      valves, the risk of systemic embolism is also seen to increase during pregnancy.
      According to data analyzed, positive antiphospholipid antibodies (APLA) as well
      as anticardiolipin antibody and lupus anticoagulant (nonspecific inhibitor)
      positivity, homozygosity and heterozygosity for factor V Leiden mutation and
      heterozygosity for the prothrombin G20210A variant, MTHFR C677T variant
      homozygosity and hyperhomocysteinemia are in strong association with pregnancy
      complications and severe pregnancy outcome. The strongest association for late
      fetal loss was seen in women with protein S deficiency. In order to reduce such
      risks, anticoagulation therapy is administered throughout pregnancy. The
      antithrombotic agents available for the prevention and treatment of VTE during
      pregnancy and pregnancy complications include unfractionated heparin (UFH), low
      molecular-weight heparin (LMWH) and aspirin. Vitamin K antagonists are
      contraindicated in pregnancy. Low-dose aspirin may have a role in the prevention
      of some pregnancy complications, although its safety in early pregnancy is
      uncertain. LMWH and UFH are quite safe and efficacious when properly selected,
      dosed and monitored. The efficacy and safety of LMWH have been demonstrated in
      the prevention and treatment of VTE in pregnancy. LMWH in association with
      aspirin administered throughout pregnancy have been shown to be associated with a
      lower risk of complications in women with APLA syndrome. Women at a high risk of
      preeclampsia are recommended to use low-dose aspirin throughout pregnancy. When
      there is a history of preeclampsia, the administration of anticoagulation therapy
      is not recommended as a prophylaxis in subsequent pregnancies, as the risk
      appears to be already decreased as compared with previous pregnancy. LMWH has
      probable advantages over UFH for the incidence of side effects. In pregnant women
      with mechanical heart valves, anticoagulant therapy during pregnancy should
      include assessment of additional risk factors for thromboembolism including valve
      type, position, and history of thromboembolism, and decision should also be
      strongly influenced by the patient's preferences. If the risk of thromboembolism
      in patients with mechanical heart valves is considered very high, and efficacy or
      safety of prophylaxis with UFH or LMWH is not satisfactory (older-generation
      prosthesis in the mitral position or history of thromboembolism), administration
      of vitamin K antagonists throughout pregnancy is recommended with replacement by
      UFH or LMWH close to delivery. It should be considered that limited effectiveness
      of UFH or LMWH in patients with mechanical heart valves might be due to
      inadequate dosing. The necessity of anticoagulation therapy in women with
      inherited or acquired thrombophilia is biologically plausible; nevertheless,
      optimum management in such cases remains unknown.

PMID- 20034332
TI  - [Colorectal cancer in Krapina-Zagorje County: the Zabok General Hospital
      experience].
AB  - AIM: To analyze data and current experience in diagnosing and treating colorectal
      cancer at Zabok General Hospital in Krapina-Zagorje County during a 5-year period
      (2002-2006). METHODS: Retrospective study of 265 cases of colorectal carcinoma
      treated at Departments of Internal Medicine and of Abdominal Surgery, Zabok
      General Hospital, and analysis of epidemiological data obtained from the Croatian
      Public Health Institute for this County. RESULTS: The incidence rate of this
      malignancy in Krapina-Zagorje County was between 47.8 and 52 per 100 000, which
      puts our County at the bottom of the list of all Croatian counties. During the
      study period, the incidence rate was on a decrease and mortality rate increased,
      which could be attributed to the late diagnosis of this malignancy (3 months of
      the occurrence of the first alarming symptoms). Most patients were men, average
      age 68. The most common symptoms were rectal bleeding, abdominal pain, anemia and
      changes in defecation habits. The average hospitalization was 13 and 17 days at
      Departments of Internal Medicine and of Abdominal Surgery, respectively. The most
      common tumor seats were rectum and sigmoid colon. Colorectal cancer was mostly
      diagnosed in an advanced stage of disease. More than one third of patients
      (35.2%) were admitted to the hospital with bowel obstruction or perforation.
      According to Duke's classification, most patients were in stage C (39.5%), D
      (22.7%) and A (6.9%). Histologic studies revealed adenocarcinoma in all but one
      case that proved to be lymphoma. CONCLUSION: We conclude that Zabok General
      Hospital has valuable experience in diagnosing and treatment of colorectal
      cancer, with high rank performance since 68.0% of patients from Krapina-Zagorje
      County are managed at this hospital.

PMID- 20034333
TI  - [Changes in visual evoked potentials curve parameters in children with
      amblyopia].
AB  - AIM: The aim of the study was to correlate visual evoked potential (VEP)
      parameters (amplitude and latency) with visual acuity of the amblyopic eye.
      PATIENTS AND METHODS: The study included 30 children aged 4.5-6 years, tested for
      visual acuity before refractive correction, with correction, and after pleoptic
      therapy. In addition, VEP parameters were recorded according to changes in visual
      acuity. RESULTS: VEP curves were found to change with visual acuity of the
      amblyopic eye. A statistically significant correlation was obtained between
      amplitude values and visual acuity as well as between latency values and visual
      acuity (P<0.001 both). DISCUSSION: Some authors have reported differences in VEP
      curve parameters according to visual acuity. We performed VEP assessment in
      children with anisometropic amblyopia and found statistically significant
      differences among the values obtained before refractive correction, with
      refractive correction and after pleoptic treatment of amblyopic eye. VEP curve
      values changed with improvement in visual acuity: the P100 wave amplitude was
      higher and latency shorter. CONCLUSION: VEP may be a valid method to determine
      amblyopia.

PMID- 20034334
TI  - [Varicella zoster myopericarditis in an immunocompetent adult].
AB  - More than 20 viruses have been reported to cause myopericarditis, a rare but
      potentially dangerous complication. To our best knowledge only a few dozen cases
      of myopericarditis caused by varicella zoster virus have been reported, most
      frequently in children, seldom in immunocompetent adults. We report on a case of
      a myopericarditis caused by varicella zoster virus in a previously healthy young
      man, with a typical development and a fast and complete recovery. A 27-years-old
      male was admitted to our hospital with chest pain and signs of acute cardiac
      injury. He had no medical history of serious previous illnesses. Four weeks
      earlier, the patient was in contact with a child having chickenpox. Two days
      prior to admission patient became suddenly febrile up to 40 degrees C along with
      dry cough, and the following day intense chest pain set in. At the admission we
      found in the patient diffuse vesiculous exanthema on the whole body and
      capillitium. Heart beat was rhythmical with no audible murmurs or pericardial
      friction rub, 100 beats per minute, blood pressure RR 130/90 mm Hg, body
      temperature 37.4 degrees C, and ST segment elevation in lateral leads along with
      elevated cardiac markers were found. All parameters of complete blood count were
      within normal range. Chest X-ray showed somewhat enlarged heart with incipient
      signs of cardiac decompensation. Echocardiogram was normal, apart from a mild
      dyskinesis of the apical third of intraventricular septum, with ejection fraction
      slightly reduced to 50% and no valvular defect. Clinical diagnosis of acute
      infection with varicella zoster virus was confirmed serologically by a positive
      ELISA test. Patient received conservative therapy (isosorbide mononitrate, low
      molecular weight heparin, acetylsalicylic acid and bisoprolol), while he remained
      hemodinamically, and apart from one non sustained ventricular tachycardia
      immediately after admission, also rhythmically stable. During his stay in
      hospital we observed the typical evolution and regression of rash while the
      levels of cardiac markers normalised, with patient becoming afebrile the third
      day. Before dismission a control echocardiograph showed improvement of
      contractile function, ejection fraction improved to 65%, but also signs of mild
      pericarditis were recorded. Since the patient had no discomfort and was in a very
      good shape, he was dismissed from hospital with ibuprofen 400 mg twice a day as
      therapy. Two months later, the patient was readmitted for control. In the mean
      time he had no discomfort, all laboratory and the physical examination findings
      were normal, as well as the ECG. Echocardiogram showed normal contractility,
      systolic and diastolic function. Cardiac stress testing and coronary angiography
      both ruled out a coronary heart disease. Diagnosis of myocarditis in this case
      was made based on echocardiogram, anamnestic data and on the typical clinical
      presentation of an acute varicella zoster virus infection, and was serologically
      confirmed by ELISA test. Therapy with NSAID was started immediately and because
      of favorable development of the disease we did not perform myocardial biopsy.
      During second hospitalization an eventual coronary heart disease was ruled out by
      coronary angiography. Due to its rarity there are no guidelines regarding therapy
      of varicella myocarditis, but there is a consensus that these patients should
      receive intensive care unit. The basis of the therapy are certainly the NSAIDs,
      but also a combination of acyclovir and hyperimmunoglobulins has been reported
      which in this mild case was not necessary. With this report we want to point out
      that varicella zoster virus can cause myopericarditis in immunocompetent adults,
      which must be taken into consideration in differential diagnosis, and that an
      early diagnosis and adequate therapy can help achieve a fast and complete
      recovery.

PMID- 20034335
TI  - [What should we know about venous and arterial ulcers?].
AB  - Chronic venous insufficiency starts by promoting the case of events. This results
      in pathologic venous and tissue changes consequential to chronic venous
      insufficiency. In this article, chronic venous insufficiency is defined as an
      abnormal function of the venous system due to venous valvular incompetence with
      or without associated venous outflow obstruction, which may involve the
      superficial venous system, deep venous system, or both. Long-term venous
      hypertension may present by a variety of clinical manifestations in terms of the
      severity and duration of venous circulation damage. Venous leg ulcer occurs in
      distal part of the shin, mostly around medial malleolus. The base of the ulcer is
      often covered by a yellowish fibrin layer. The surrounding skin is
      hyperpigmented, usually irritated by ulcer secretion, and inflamed. Arterial leg
      ulcer is caused by arterial insufficiency. It is round-shaped with dry basis and
      involves deeper structures, up to tendons. The skin is dry, atrophic, cool, pale,
      smooth, and hairless. Therapy of ulcers is demanding and consists of numerous
      general measures, topical and/or systemic therapy. Topical therapy consists of
      cleansing, mechanical debridement, disinfection and stimulation of granulations
      and epithelialization with prevention of secondary infection. Therapy with
      currently available bio-occlusive wound dressings is most effective. These
      dressings are hydrocolloids, hydropolymers, transparent films, alginate, and
      ionic silver. Vascular protectors, venetonics and antiaggregation medications can
      be used in systemic therapy.

PMID- 20034336
TI  - [The hospice movement in Croatia--short review].
AB  - The hospice movement was launched by the Croatian Society of Hospice and
      Palliative Care, Croatian Medical Association, founded and headed by the author
      until 2009. In this article, the author describes the development of the hospice
      movement in four periods, as follows: first period 1994-1999, the beginnings;
      second period 2000-2005, a period of great hopes and initial achievement of first
      goals; third period 2006-2008, a period of stagnation, the 'burn-out' syndrome,
      looking for new ways and people; and fourth period 2009-? Let us hope it will
      bring true finding way out, a new period of struggling for acceptable solutions,
      which has already been accomplished in many countries. The hope dies last, the
      hope in positive powers among the citizens of Croatia. Only the most important
      facts are presented, whereas citations from numerous lectures, events held all
      over Croatia and publications in many books and newspapers are omitted.
      Descriptions of numerous trips for training, education, for one month, two weeks,
      one week or several days in the USA, Canada, UK, Poland, Hungary, Austria,
      Switzerland, Norway, etc., and of visits paid by many guests from the UK, USA,
      Canada, Italy, Germany, Switzerland, Poland, Hungary, Romania, Bulgaria, Israel,
      Bosnia and Herzegovina, Serbia, Macedonia, etc. are also omitted. All these facts
      will be presented in the monograph that has been prepared for publication.

PMID- 20034337
TI  - Breastfeeding in HIV-positive women: What can be recommended?
AB  - Breastfeeding remains a common practice in parts of the world where the burden of
      HIV is highest and the fewest alternative feeding options exist. The impossible
      dilemma faced by HIV-positive mothers is whether to breastfeed their infants in
      keeping with cultural norms but in doing so risk transmitting the virus through
      breast milk, or to pursue formula feeding, which comes with its own set of risks,
      including a higher rate of infant mortality from diarrheal illnesses, while
      reducing transmission of HIV. Treatment of mothers and/or their infants with
      antiretroviral drugs is a strategy that has been employed for several decades to
      reduce HIV transmission through pregnancy and delivery, but the effect of these
      agents when taken during breastfeeding is a newer field of study. In this article
      we evaluate the latest clinical research, from trials that encourage exclusive
      breastfeeding to trials of antiretroviral therapy (ART) for either the mother or
      infant, in an attempt to prevent transmission of HIV through breast milk.
      Additionally, we discuss research that is in progress, with results anticipated
      in the next few years that will further shape clinical guidelines and practice.
      Exclusive breastfeeding is much safer than mixed feeding (the supplementation of
      breastfeeding with other foods), and should be encouraged even in settings where
      ART for either the mother or infant is not readily available. The research
      published regarding maternal treatment with highly active antiretroviral therapy
      (HAART) during pregnancy and the breastfeeding period has all been non-randomized
      with relatively little statistical power, but suggests maternal HAART can
      drastically reduce the risk of transmission of HIV. Infant prophylaxis has been
      intensively studied in several trials and has been shown to be as effective as
      maternal treatment with antiretrovirals, reducing the transmission rate after 6
      weeks to as low as 1.2%. Research that is in progress will provide us with more
      answers about the relative contribution of maternal treatment and infant
      prophylaxis in preventing transmission, and the results of such research may be
      expected as early as this year through 2013. There is hope that perinatal HIV
      transmission may be greatly reduced in breastfeeding populations worldwide
      through a combination of behavioral interventions that encourage exclusive
      breastfeeding and pharmacologic interventions with antiretrovirals for mothers
      and/or their infants.

PMID- 20034338
TI  - Juvenile myelomonocytic leukemia: epidemiology, etiopathogenesis, diagnosis, and
      management considerations.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare hematopoietic malignancy of
      early childhood with features characteristic of both myelodysplastic and
      myeloproliferative disorders. Recent studies clearly show that the deregulated
      activation of the RAS signaling pathway plays a central role in the pathogenesis
      of JMML. Somatic defects in either RAS, PTPN11 or NF1 genes involved in this
      pathway are detected in 70-80% of JMML patients, allowing a molecular diagnosis
      to be made in the majority of cases. Patients with JMML respond poorly to
      chemotherapy, and the probability of survival without allogeneic hematopoietic
      stem cell transplantation (HSCT) is less than 10%. Recent studies show that the
      event-free survival after HSCT is between 24 and 54%, with no difference between
      transplants using matched family donors and those using unrelated donors. The use
      of therapies such as intensive chemotherapy and splenectomy prior to HSCT does
      not improve the outcome. The relapse rate following HSCT is over 30%, which is
      unacceptably high. Cumulative evidence suggests that a graft-versus-leukemia
      effect occurs in JMML. Donor leukocyte infusion is not usually successful in
      JMML, but the outcome of second HSCT is generally favorable. Based on recent
      advances in the understanding of the pathogenesis of JMML, the development of
      novel targeted therapies, which might improve the outcome of patients, is keenly
      awaited.

PMID- 20034339
TI  - Juvenile-onset clinically amyopathic dermatomyositis: an overview of recent
      progress in diagnosis and management.
AB  - Juvenile-onset amyopathic dermatomyositis is an uncommon variant of juvenile
      onset dermatomyositis (JDM), characterized by the hallmark cutaneous features of
      dermatomyositis for at least 6 months without clinical or laboratory evidence of
      muscle disease. Cutaneous calcinosis, vasculopathy, and interstitial lung disease
      frequently complicate the course of classic JDM (typical JDM with myositis) but
      are infrequent in amyopathic JDM. Recent literature suggests that approximately
      75% of amyopathic JDM patients will remain free from muscle disease after years
      of follow-up, while approximately 25% of patients will evolve to having classic
      JDM. No clinical, laboratory, or ancillary parameters have been found to be
      predictive for this transition to muscle disease. Treatment of the cutaneous
      disease of amyopathic JDM centers on photoprotection and topical therapies
      directed against inflammation. Oral antimalarials are effective for cutaneous
      disease not adequately controlled with topical care. Systemic corticosteroids,
      while central to the treatment of classic JDM, are controversial in the treatment
      of amyopathic JDM. Randomized controlled trials are not available to guide the
      management of this disease. Proponents for early aggressive systemic
      corticosteroid therapy for amyopathic JDM advocate that this intervention may
      decrease the likelihood of progression to classic JDM, and/or prevent disease
      specific complications of JDM such as calcinosis. Opponents of early intervention
      with systemic corticosteroids favor expectant management directed toward
      controlling skin disease, citing the predictable adverse effects of systemic
      corticosteroids in the face of uncertain benefit. Other therapeutic options for
      severe and recalcitrant cutaneous disease, including methotrexate, intravenous
      immunoglobulin, and rituximab, are reviewed, as are treatment options for
      calcinosis cutis. In weighing the available evidence, the authors conclude that
      early aggressive treatment of amyopathic JDM with systemic immunosuppressant
      agents should be avoided in most cases as the risk of these medications will
      outweigh the measurable benefit. The reported literature suggests a good
      prognosis for amyopathic JDM. Ongoing clinical follow-up is recommended in all
      cases to allow early detection of subtle signs of muscle disease.

PMID- 20034340
TI  - Adverse effects of immunosuppression in pediatric solid organ transplantation.
AB  - Solid organ transplantation is a life-saving treatment for end-stage organ
      failure in children. Immunosuppressant medications are used to prevent rejection
      of the organ transplant. However, these medications are associated with
      significant adverse effects that impact growth and development, quality of life
      (QOL), and sometimes long-term survival after transplantation. Adverse effects
      can differ between the immunosuppressants, but many result from the overall state
      of immunosuppression. Strategies to manage immunosuppressant adverse effects
      often involve minimizing exposure to the drugs while balancing the risk for
      rejection. Early recognition of immunosuppressant adverse effects may help to
      reduce morbidities associated with solid organ transplantation, improve QOL, and
      possibly increase overall patient survival.

PMID- 20034341
TI  - Optimizing emetic control in children receiving antineoplastic therapy: beyond
      the guidelines.
AB  - Existing guidelines for the prevention of antineoplastic chemotherapy-induced
      nausea and vomiting (CINV) in children are constrained by the lack of robust
      evidence. Current guidelines recommend the use of a serotonin 5-HT(3) receptor
      antagonist plus a corticosteroid to prevent acute CINV. Consequently, antiemetic
      agents that are recommended for use in adult cancer patients do not appear in the
      current pediatric guidelines. In addition, there is no information to guide the
      selection of alternative antiemetic agents for children who either cannot receive
      the recommended agents or who do not respond adequately to the treatment.
      Possible barriers to adherence to the pediatric antiemetic selection guidelines
      that are currently available are discussed, and published pediatric experience
      with antiemetic agents recommended in the current adult antiemetic selection
      guidelines (dolasetron, tropisetron, palonosetron, aprepitant) is summarized in
      this review. The use of novel and emerging antiemetic therapeutic interventions
      {metopimazine, diphenhydramine (Benadryl)-lorazepam (Avitan)-dexamethasone
      (Decadron) [BAD], nabilone, acupuncture, midazolam, olanzapine, mirtazapine,
      gabapentin, droperidol} in children are explored.

PMID- 20034342
TI  - Bosentan: in pediatric patients with pulmonary arterial hypertension.
AB  - Bosentan is a dual endothelin-1 (ET-1) receptor antagonist that has affinity for
      ET-1 receptors A and B. In the EU, oral bosentan (Tracleer) is indicated to
      improve exercise capacity and symptoms in patients with pulmonary arterial
      hypertension (PAH) of WHO functional class III; benefits have also been seen in
      patients with WHO functional class II PAH. Bosentan is available as film-coated
      tablets, and a new dispersible formulation of bosentan has also recently been
      approved in the EU for the treatment of PAH in children aged > or =2 years. A
      noncomparative, multicenter, phase III trial (FUTURE-1), which was primarily
      designed to investigate the pharmacokinetics of dispersible bosentan in pediatric
      patients, demonstrated that increasing the dosage of bosentan from 2 to 4 mg/kg
      twice daily was unlikely to result in increased exposure to bosentan. Exploratory
      measures of efficacy in FUTURE-1 demonstrated that target dosages of twice-daily
      dispersible bosentan 4 mg/kg (in patients weighing <30 kg) or 120 mg (in patients
      weighing > or =30 kg) for 12 weeks were beneficial in pediatric patients (aged >
      or =2 to <12 years) with WHO functional class II or III PAH. Film-coated bosentan
      31.25, 62.5, or 125 mg (in pediatric patients weighing 10-20, >20-40, or >40 kg,
      respectively) twice daily for 12 weeks significantly (p < 0.05) improved the
      majority of hemodynamic measures evaluated as an exploratory measure in pediatric
      patients (aged 3-15 years) with WHO functional class II or III PAH in another
      noncomparative, multicenter, pharmacokinetic trial (BREATHE-3). However, there
      was no significant change in peak oxygen consumption or mean walk distance in
      those patients capable (i.e. children aged > or =8 years) of performing the 6
      minute walk test. Bosentan was generally well tolerated in clinical trials of
      pediatric patients with PAH, with most adverse events being mild or moderate in
      severity and resolving with continued treatment.

PMID- 20034343
TI  - Is high vancomycin minimum inhibitory concentration a good marker to predict the
      outcome of methicillin-resistant Staphylococcus aureus bacteremia?

PMID- 20034346
TI  - A woman with HIV infection, brain abscesses, and eosinophilia.

PMID- 20034345
TI  - Diagnosis and management of complicated intra-abdominal infection in adults and
      children: guidelines by the Surgical Infection Society and the Infectious
      Diseases Society of America.
AB  - Evidence-based guidelines for managing patients with intra-abdominal infection
      were prepared by an Expert Panel of the Surgical Infection Society and the
      Infectious Diseases Society of America. These updated guidelines replace those
      previously published in 2002 and 2003. The guidelines are intended for treating
      patients who either have these infections or may be at risk for them. New
      information, based on publications from the period 2003-2008, is incorporated
      into this guideline document. The panel has also added recommendations for
      managing intra-abdominal infection in children, particularly where such
      management differs from that of adults; for appendicitis in patients of all ages;
      and for necrotizing enterocolitis in neonates.

PMID- 20034348
TI  - Serum cytokine levels in postinfective fatigue syndrome.

PMID- 20034349
TI  - In nonendemic areas, is microscopy better than polymerase chain reaction for
      diagnosis of congenital chagas disease?

PMID- 20034351
TI  - Studies on severe malaria are still possible and essential.

PMID- 20034352
TI  - Severe malaria studies: challenge to balance clinical medicine and public health.

PMID- 20034353
TI  - Heparin-binding protein: a potential biomarker in sepsis?

PMID- 20034354
TI  - Implementing universal oral HIV screening in an urban emergency department-do
      demographic characteristics impact acceptance of testing?

PMID- 20034356
TI  - Serum Antibody Response to the Novel Influenza A (H1N1) Virus in the Elderly.

PMID- 20034360
TI  - Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic
      response during Crohn's disease treatment.
AB  - OBJECTIVE: Serial monitoring data for faecal calprotectin and lactoferrin during
      Crohn's disease (CD) therapy are scarce. The aim of this research was to study
      the behaviour of faecal biomarkers during CD therapy. MATERIAL AND METHODS: Adult
      CD patients (n = 19) needing therapy enhancement were prospectively recruited.
      The simple endoscopic score for Crohn's disease (SES-CD) was administered before
      and 4-6 months after therapy. At baseline and at 2-3 and 4-6 months, patients
      provided faecal samples for measurements of calprotectin and lactoferrin.
      RESULTS: Of 19 patients, seven were endoscopic responders, three were partial
      responders and nine were non-responders. During therapy, both faecal-biomarker
      concentrations decreased significantly in responders: median calprotectin from
      1282 microg/g (range 156-2277 microg/g) to 73 microg/g (range 7-2222; P = 0.005)
      and lactoferrin from 233 microg/g (range 2.8-802 microg/g) to 0.0 microg/g (range
      0.0-420 microg/g; P = 0.005), and these changes correlated significantly with
      changes in the SES-CD. In non-responders, changes in faecal biomarkers were non
      significant: calprotectin decreased from 1017 microg/g (range 53-3928 microg/g)
      to 223 microg/g (range 35-15330 microg/g; P = 0.594) and lactoferrin from 22.5
      microg/g (range 2.1-629 microg/g) to 13.0 microg/g (range 3.5-1259 microg/g; P =
      0.515). CONCLUSIONS: The faecal neutrophil-derived proteins calprotectin and
      lactoferrin are reliable surrogate markers of mucosal improvement. Endoscopic
      responders achieved normalization of faecal biomarkers, whereas in the majority
      of endoscopic non-responders these markers remained abnormal.

PMID- 20034361
TI  - Diagnostic yield and reliability of endoscopic ultrasonography in patients with
      idiopathic acute pancreatitis.
AB  - OBJECTIVES: To evaluate the diagnostic yield of endoscopic ultrasonography (EUS)
      in patients with idiopathic acute pancreatitis (IAP), find factors predictive of
      a positive EUS finding in these patients and investigate whether these
      etiological findings are maintained during follow-up. MATERIAL AND METHODS: We
      performed EUS in patients with IAP between July 2004 and August 2007. We recorded
      epidemiological data, the number and severity of previous bouts of pancreatitis
      and gallbladder status. RESULTS: A total of 44 patients were included in the
      study. EUS was normal in seven patients (16%). In the remaining 37 patients (84%)
      we found cholelithiasis (n = 3), microlithiasis (n = 20), chronic pancreatitis (n
      = 14), pancreas divisum (n = 3), pancreatic mass (n = 1), apudoma (n = 1), cystic
      tumor of the pancreas (n = 2) and choledocholithiasis (n = 2). Positive EUS
      findings were not influenced by sex, severity of pancreatitis or recurrent
      disease. Patients aged < 65 years (age > or < 65 years: 73.9% versus 95.2%; P =
      0.097) and patients with gallbladder in situ (cholecystectomy versus non
      cholecystectomy: 63.6% versus 90.9%; P = 0.054) showed a tendency to have
      positive EUS findings. Mean follow-up was 28.95 +/- 10.86 months (range 12-64
      months; median 28 months). During follow-up the etiological diagnosis was changed
      in two patients, lowering the diagnostic yield to 79%. CONCLUSIONS: EUS
      identified the cause of IAP in 79% of patients. Patients with gallbladder in situ
      and patients aged < 65 years showed a tendency to have positive EUS findings. The
      majority of the diagnoses provided by EUS are maintained during follow-up and
      seem to be reliable.

PMID- 20034362
TI  - Effect of pravastatin on kidney function and urinary protein excretion in
      autosomal dominant polycystic kidney disease.
AB  - OBJECTIVE: Autosomal dominant polycystic kidney disease (ADPKD) is progressive,
      resulting in end-stage kidney failure in most patients. Experimental and clinical
      studies have suggested that statins may slow the progression of chronic kidney
      disease in general and ADPKD specifically. MATERIAL AND METHODS: This randomized
      open-label clinical trial was conducted to assess the effect of pravastatin 20 mg
      on kidney function and urinary protein excretion in patients with ADPKD. Sixty
      patients were initially recruited but 49 of these received either pravastatin 20
      mg or no treatment for 2 years. Trial visits were conducted every 3 months,
      assessing kidney function by estimated glomerular filtration rate and 24 h urine
      creatinine clearance and urinary protein excretion. RESULTS: There were no
      significant (p > 0.05) changes in markers of kidney function or urinary protein
      excretion between groups over the 2 years despite a significant fall in total
      serum cholesterol in pravastatin-treated patients (p = 0.029). CONCLUSION: This
      trial found that taking 20 mg pravastatin for 2 years had no significant effect
      on kidney function or urinary protein excretion in patients with ADPKD. The lack
      of statistical power limits the external validity of these findings. A larger,
      longer duration study using a higher dose of a more potent statin is required.

PMID- 20034363
TI  - Immunomodulation with heat shock protein DiaPep277 to preserve beta cell function
      in type 1 diabetes - an update.
AB  - IMPORTANCE OF THE FIELD: Type 1 diabetes is a chronic autoimmune disease in which
      pancreatic beta cells are selectively destroyed. Ultimately hyperglycemia
      develops and insulin substitution becomes necessary. Immunomodulation aims at
      arresting this autoimmune attack. DiaPep277, the major T-cell epitope of heat
      shock protein 60 (hsp60), has been shown to be effective as a modulator of the
      immune system in type 1 diabetes and is the focus of this review. AREAS COVERED
      IN THIS REVIEW: A literature search of Pubmed listed publications covering 1990 -
      2009 and a website search of the licensing company were performed. WHAT THE
      READER WILL GAIN: DiaPep277 has been successfully employed in animal models and
      has been investigated in Phase I - III studies in humans. A combined analysis of
      the Phase II trials showed a significant preservation of beta cell function in
      adults without adverse effects, but HbA1c was not changed. A Phase III clinical
      trial is ongoing, and a second Phase III trial will start in early 2010.
      Addressing the underlying autoimmune process is the call of the future in type 1
      diabetes. TAKE HOME MESSAGE: Use of Diapep277 is a promising therapeutic strategy
      currently being tested in Phase III trials.

PMID- 20034365
TI  - Review of the relationship between renal and retinal microangiopathy in diabetes
      mellitus patients.
AB  - Diabetes mellitus is a group of metabolic disorders of carbohydrate metabolism in
      which glucose is underutilized, producing hyperglycemia. The latter complications
      of diabetes mellitus include microvascular complications the major microvascular
      complications, retinopathy and nephropathy, are the more important causes of
      blindness and end-stage renal disease in Europe. Different risk factors such as
      diabetes duration, blood pressure and lipid control have consistently been shown
      to correlate with both microvascular complications for diabetes. Despite the
      efforts of studies to correlate the two major diabetes mellitus microvascular
      complications, retinopathy and nephropathy, the relationship has not so far been
      clearly described. However, the currently literature data suggest that the
      presence of a pre-existing microvascular complication (retinopathy or
      nephropathy) may contribute to the development of another, especially in DM1
      patients. More prospective studies are needed if we are to know the exact
      mechanism of how these diabetic microvascular diseases correlate, and if we are
      to develop a scoring system for predicting the development of those complications
      that will allow us to identify the patients at risk, with its consequent positive
      impact on patients' quality of life. The aim of the present study is to review
      the literature on the diagnosis, epidemiology, pathology, and risk factors in
      diabetic nephropathy and retinopathy, and then a revision of the possible
      relation between renal and retinal diabetic microangiopathy.

PMID- 20034366
TI  - A review of maternal and fetal growth factors in diabetic pregnancy.
AB  - Diabetes mellitus complicates 1-2% of all pregnancies but is associated with high
      perinatal morbidity and mortality. Gestational diabetes affects up to 4% of
      pregnancies and is associated with fetal macrosomia (large for dates). Fetal
      growth is a complex process influenced by determinants such as genetics, maternal
      factors, uterine environment and maternal and fetal hormones. Infants of pre
      gestational diabetic mothers have an additional influence of maternal
      fluctuations in glycaemia. The purpose of this paper is to review maternal and
      fetal growth factors, including insulin, in the aetiology of macrosomia in
      diabetic pregnancy. Placental Growth Hormone is the major growth hormone secreted
      during human pregnancy. Leptin may have a role in satiety. Resistin was
      originally proposed as the link between obesity and diabetes but is now thought
      to have a more complex role. These hormones and their actions on human in-utero
      growth are reviewed in depth with particular reference to both pre-gestational
      (type 1 and type 2 diabetes) and gestational diabetes. Previously increased fetal
      weight in infants of diabetic mothers was thought to be as a result of maternal
      hyperglycaemia. It is now evident that control of fetal growth, in normal as well
      as diabetic pregnancies, is far more complex than previously thought.

PMID- 20034367
TI  - New-onset hyperglycemia and acute coronary syndrome: a systematic overview and
      meta-analysis.
AB  - BACKGROUND: Patients without a history of diabetes often develop hyperglycemia
      during an acute coronary syndrome (ACS). New onset of hyperglycemia (NH) is
      associated with higher mortality both in the short and long-term. AIM: We
      performed a systematic review and meta-analysis of observational studies to
      investigate the association between NH and mortality in patients with ACS. In
      hospital, 30-day and long-term mortality were analyzed separately. METHODS: We
      searched MEDLINE for prospective studies of patients with ACS reporting the
      association between NH and mortality, using Research Methodology Filters. This
      was supplemented by hand searching reference lists of retrieved articles. We
      determined study eligibility and conducted data abstraction independently and
      disagreements were resolved by consensus. We pooled odds ratios (OR) from
      individual studies using a random effects model. RESULTS: Our search strategy
      identified 24 studies. The prevalence of NH varied widely 3% to 71% depending on
      the definition of NH used. NH significantly increased the risk of in-hospital (OR
      3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies, 10673 patients), 30
      day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4 studies, 101447
      patients), and long-term (up to 108 months) mortality (OR 2.02, 95% CI: 1.62
      2.51; p < 0.0001, I2=79.4%; 12 studies, 102099 patients). CONCLUSIONS: In
      patients without a prior diagnosis of diabetes who are admitted to hospital for
      ACS, NH increases the risk of both short and long-term mortality. These data
      highlight the need for further studies addressing the control of blood glucose
      levels in patients with ACS. SUMMARY: Patients without history of diabetes may
      develop new hyperglycemia (NH) on admission to hospital for AMI. We
      systematically reviewed the prognostic impact of NH on short- and long-term
      mortality in patients without prior diagnosis of diabetes who attended the
      hospital for ACS. We identified 24 outcome studies which met a set of pre
      specified criteria. Prevalence of NH ranged from 3% to 71% according to different
      thresholds of blood glucose concentrations. NH significantly increased the risk
      of in-hospital (OR 3.62, 95% CI: 3.09 - 4.24; p < 0.0001, I2=0.0%; 15 studies,
      10673 patients), 30-day (OR 4.81, 95% CI: 2.18 - 10.61, p < 0.0001, I2=92.2%; 4
      studies, 101447 patients)), and long-term (up to 108 months) mortality (OR 2.02,
      95% CI: 1.62-2.51; p < 0.0001, I2=79.4%; 12 studies, 102,099 patients).

PMID- 20034368
TI  - Advanced Diabetes care: three levels of prediction, prevention & personalized
      treatment.
AB  - Worldwide epidemic scale of Diabetes mellitus (DM) has been underestimated for a
      long time. Currently every 10 seconds one patient dies of diabetes-related
      pathologies. Given the high risk and prevalence of secondary complications as
      well as individual predisposition to target organ injury, DM is one of the best
      examples for the application of predictive diagnostics aimed at preventive
      measures and personalized treatment approaches. Generally there are three levels
      in desirable pre- and Diabetes care: 1st level: prediction of the predisposition
      early in childhood. 2nd level: prediction of early/premature aging and prestages
      of Diabetes. 3rd level: prediction of Diabetes-related complications -
      cardiovascular, neurodegenerative and cancer diseases frequently developed in
      Diabetics. Predictive diagnosis is considered as the basis for targeted
      preventive measures and consequent creation of individualized treatment
      approaches. Communication among the professionals - healthcare providers, policy
      makers, educators, etc., obligatory involved in the overall process to improving
      (pre)Diabetes care is of paramount importance.

PMID- 20034369
TI  - Cardiovascular and renal complications of type 2 diabetes in obesity: role of
      sympathetic nerve activity and insulin resistance.
AB  - Overweight and obesity is a growing "world-wide epidemic problem". Because as
      many as, two-thirds of the adult population and a growing number of children are
      overweight. The prevalence of diabetes, especially type 2 diabetes and
      hypertension have significantly increased with the prevalence of obesity. Obesity
      accompanying type 2 diabetes and hypertension are known to be closely linked with
      insulin resistance and elevated sympathetic nervous activity. It has been well
      documented that obesity, hypertension, and diabetes are high risk factors for
      subsequent cardiovascular and renal complications. Many patients are both
      diabetic and hypertensive, while they are obese, but not all diabetic patients
      have hypertension, indicating that insulin resistance is not only a mechanism for
      blood pressure elevation in diabetic-hypertensive patients. Several investigators
      have reported that sympathetic nervous activation relates to cardiovascular
      complications in patients with hypertension, diabetes, and obesity, and that
      sympathetic nerve activity accompanying insulin resistance is closely linked with
      left ventricular hypertrophy in healthy subjects. In addition, sympathetic nerve
      activation may predict future renal injury in healthy normotensive subjects.
      These findings suggest that elevated sympathetic nerve activity associated with
      insulin resistance may contribute to the onset and maintenance of cardiovascular
      and renal complications in diabetes, and hypertension in obesity. Further,
      genetic polymorphisms of the beta2- and beta3-adrenoceptor gene have been
      associated with type-2 diabetes and insulin resistance in many epidemiological
      studies and might be another factor responsible for the close relationship
      between insulin resistance and heightened sympathetic nerve activity. Thus,
      focusing on the interactions between insulin resistance, sympathetic nervous
      activity and beta-adrenoceptor polymorphisms might help in understanding the
      precise relationships between insulin resistance and sympathetic nerve activity
      in type 2 diabetes and obesity-related hypertension. The purpose of this article
      is to provide a synthesis of the current findings on the mechanisms of the onset
      and maintenance of cardiovascular and renal complications in obesity, diabetes
      and hypertension. A better understanding of the relationships of sympathetic
      nervous system activity and insulin resistance might help with the clinical
      treatment of diabetes and hypertension in obesity. Further, to clarify the
      pathogenesis and mechanisms of the association between obesity, diabetes, and
      hypertension may lead to reductions in cardiovascular and renal risk.

PMID- 20034370
TI  - Zinc, alpha cells and glucagon secretion.
AB  - Zinc concentrates in islet cells and is related to insulin secretion. Islet cells
      act as a unit within islets and hormone secretion in the islets is profoundly
      influenced by paracrine and autocrine regulation. Zinc has been recognised as a
      candidate paracrine inhibitor of glucagon secretion in alpha-cells. Further zinc
      fluxes may contribute to regulation of cell mass, Zn2+ may be cytotoxic and Zn2+
      depletion by itself can cause cell death induced by oxidative stress. Recently,
      both free zinc ions and a number of zinc transporters have been localized in
      alpha-cells. These include zinc importers, ZIP1, ZIP10, and ZIP14 of the SLC39A
      family and zinc exporters, ZnT1, and ZnT4-8 of the SLC30A family. Furthermore,
      the redox state of thiol groups and Voltage Gated Ca2+ Channels (VGCC) add to the
      maintenance of a tight cytoplasmatic zinc homeostasis in the alpha-cells. The
      ZnT8 protein has emerged as particularly interesting since this zinc transporter
      has been identified as a genetic risk factor for the development of both type 1
      and type 2 diabetes in which both alpha- and beta-cell functions are affected.
      Recent data discussed here suggest specific effects of Zn2+ on glucagon secretion
      and other alpha-cell functions.

PMID- 20034371
TI  - The connection between C-reactive protein (CRP) and diabetic vasculopathy. Focus
      on preclinical findings.
AB  - Current evidence supports a central role of inflammation in the pathogenesis of
      atherosclerosis and diabetes. Type 2 diabetes is an inflammatory atherothrombotic
      condition associated with a high prevalence of cardiovascular disease. In
      patients with type 2 diabetes, low grade inflammation is reflected by increased
      plasma levels of several biomarkers of inflammation such as C-reactive protein
      (CRP). Small increases in CRP predict the likelihood of developing cardiovascular
      events both in diabetic and nondiabetic populations. In addition, in apparently
      healthy subjects, increased levels of CRP predict the risk of developing type 2
      diabetes. There is some evidence that CRP, besides its predictive role in
      determining cardiovascular risk, may represent an active participant in
      atherogenesis. CRP is expressed in human atherosclerotic plaques and both
      vascular cells and monocytes/macrophages appear to represent a significant source
      of CRP in the inflammatory vessel wall. By activating the main cell types present
      in the atherosclerotic lesions, CRP generated within the coronary plaques may
      contribute to the development and progression of atherosclerosis. Data on
      vascular CRP regulation are scarce. Current evidence suggests that inflammatory
      and metabolic factors associated with diabetes, such as high glucose, adipokines,
      modified lipoproteins and free fatty acids may trigger CRP production by
      endothelial cells, smooth muscle cells and monocytes/macrophages. These data
      suggest that local CRP concentration in diabetic atherosclerotic plaques could be
      higher than in nondiabetic ones. Given the possible correlation between local CRP
      production and the degree of severity of coronary artery disease or the nature of
      the lesion, such alteration may contribute to the accelerated development of
      vascular disease in patients with type 2 diabetes.

PMID- 20034372
TI  - Cystic fibrosis related diabetes mellitus - diagnostic and management challenges.
AB  - Cystic fibrosis (CF) is the commonest autosomal recessive condition among
      Caucasian populations, affecting 1 in 2500 live births. The median age of
      survival has dramatically improved and will reach 40 years for children born in
      the 1990s. Complications such as cystic fibrosis related diabetes mellitus (CFRD)
      develop with age, and the median age at diagnosis is 21 years. The prevalence of
      CFRD progressively increases from 9% below the age of 10 years to 43% above the
      age of 30 years, with reported annual age-dependent incidence rates ranging from
      4% to 9%. The onset of CFRD is insidious and annual screening using the standard
      oral glucose tolerance test (OGTT) from the age of 10 years has been recommended.
      However, OGTT thresholds for the diagnosis of impaired glucose tolerance and CFRD
      were derived from epidemiological studies of non-CF patients and it is uncertain
      whether they are appropriate for patients with CF. The ability of OGTT alone to
      detect early abnormalities in blood glucose regulation has been questioned.
      Continuous glucose monitoring systems (CGMS) may augment the screening and
      diagnosis of CFRD, as well as guide and monitor its management. Subcutaneous
      insulin therapy is currently recommended for the treatment of CFRD. Early use of
      insulin therapy might improve weight gain and lung function of CF patients,
      including those with normal OGTT results. It is still not clear when insulin
      therapy should be started, possibly reflecting the difficulties in detecting
      early but clinically relevant abnormalities in blood glucose metabolism among CF
      patients. We review the current evidence which highlight these diagnostic and
      management challenges in CFRD.

PMID- 20034373
TI  - UKPDS Risk Engine, decode and diabetes PHD models for the estimation of
      cardiovascular risk in patients with diabetes.
AB  - Individuals with type 2 diabetes have a two to four fold increased risk for
      developing cardiovascular disease than persons without diabetes. The presence of
      traditional and nontraditional risk factors that frequently coexist with type 2
      diabetes are associated with this higher cardiovascular risk. Diabetes itself has
      been considered a cardiovascular disease equivalent. Nevertheless, the American
      Diabetes Association has recognized that absolute risk for cardiovascular disease
      varies among individuals with diabetes and has recommended the use of designed
      models and algorithms to estimate risk, especially in younger patients (<40
      years). Cardiovascular risk is best evaluated with an estimation that takes into
      account the individual's characteristics and risk factors. The algorithms and
      models that have been designed specifically for the assessment of cardiovascular
      risk in individuals with diabetes will be the subject of this review.
      Specifically, the DECODE (Diabetes Epidemiology: Collaborative analysis of
      Diagnostic criteria in Europe) equation has been shown to have discriminative
      capacity of 0.67; the UKPDS Risk Engine model is reported to have a sensitivity
      of around 90% and specificity of 33%; and the Diabetes Personal Health Decisions
      (PHD) in our study had a sensitivity of 67% and specificity of 41%. In this
      review we will discuss the pros and cons of each model, their use in clinical
      practice and the application of the UKPDS risk engine and PHD model in a Mexican
      population.

PMID- 20034374
TI  - Innovative approach for transcriptomic analysis of obligate intracellular
      pathogen: selective capture of transcribed sequences of Ehrlichia ruminantium.
AB  - BACKGROUND: Whole genome transcriptomic analysis is a powerful approach to
      elucidate the molecular mechanisms controlling the pathogenesis of obligate
      intracellular bacteria. However, the major hurdle resides in the low quantity of
      prokaryotic mRNAs extracted from host cells. Our model Ehrlichia ruminantium
      (ER), the causative agent of heartwater, is transmitted by tick Amblyomma
      variegatum. This bacterium affects wild and domestic ruminants and is present in
      Sub-Saharan Africa and the Caribbean islands. Because of its strictly
      intracellular location, which constitutes a limitation for its extensive study,
      the molecular mechanisms involved in its pathogenicity are still poorly
      understood. RESULTS: We successfully adapted the SCOTS method (Selective Capture
      of Transcribed Sequences) on the model Rickettsiales ER to capture mRNAs.
      Southern Blots and RT-PCR revealed an enrichment of ER's cDNAs and a diminution
      of ribosomal contaminants after three rounds of capture. qRT-PCR and whole-genome
      ER microarrays hybridizations demonstrated that SCOTS method introduced only a
      limited bias on gene expression. Indeed, we confirmed the differential gene
      expression between poorly and highly expressed genes before and after SCOTS
      captures. The comparative gene expression obtained from ER microarrays data, on
      samples before and after SCOTS at 96 hpi was significantly correlated (R2 = 0.7).
      Moreover, SCOTS method is crucial for microarrays analysis of ER, especially for
      early time points post-infection. There was low detection of transcripts for
      untreated samples whereas 24% and 70.7% were revealed for SCOTS samples at 24 and
      96 hpi respectively. CONCLUSIONS: We conclude that this SCOTS method has a key
      importance for the transcriptomic analysis of ER and can be potentially used for
      other Rickettsiales. This study constitutes the first step for further gene
      expression analyses that will lead to a better understanding of both ER
      pathogenicity and the adaptation of obligate intracellular bacteria to their
      environment.

PMID- 20034375
TI  - Activation of PKA, p38 MAPK and ERK1/2 by gonadotropins in cumulus cells is
      critical for induction of EGF-like factor and TACE/ADAM17 gene expression during
      in vitro maturation of porcine COCs.
AB  - OBJECTIVES: During ovulation, it has been shown that LH stimulus induces the
      expression of numerous genes via PKA, p38 MAPK, PI3K and ERK1/2 in cumulus cells
      and granulosa cells. Our recent study showed that EGF-like factor and its
      protease (TACE/ADAM17) are required for the activation of EGF receptor (EGFR),
      cumulus expansion and oocyte maturation of porcine cumulus-oocyte complexes
      (COCs). In the present study, we investigated which signaling pathways are
      involved in the gene expression of EGF-like factor and in Tace/Adam17 expression
      in cumulus cells of porcine COC during in vitro maturation. METHODS: Areg, Ereg,
      Tace/Adam17, Has2, Tnfaip6 and Ptgs2 mRNA expressions were detected in cumulus
      cells of porcine COCs by RT-PCR. Protein level of ERK1/2 phosphorylation in
      cultured cumulus cells was analyzed by westernblotting. COCs were visualized
      using a phase-contrast microscope. RESULTS: When COCs were cultured with FSH and
      LH up to 2.5 h, Areg, Ereg and Tace/Adam17 mRNA were expressed in cumulus cells
      of COCs. Areg, Ereg and Tace/Adam17 gene expressions were not suppressed by PI3K
      inhibitor (LY294002), whereas PKA inhibitor (H89), p38 MAPK inhibitor (SB203580)
      and MEK inhibitor (U0126) significantly suppressed these gene expressions.
      Phosphorylation of ERK1/2, and the gene expression of Has2, Tnfaip6 and Ptgs2
      were also suppressed by H89, SB203580 and U0126, however, these negative effects
      were overcome by the addition of EGF to the medium, but not in the U0126
      treatment group. CONCLUSION: The results showed that PKA, p38 MAPK and ERK1/2
      positively controlled the expression of EGF-like factor and TACE/ADMA17, the
      latter of which impacts the cumulus expansion and oocyte maturation of porcine
      COCs via the EGFR-ERK1/2 pathway in cumulus cells.

PMID- 20034376
TI  - The malate synthase of Paracoccidioides brasiliensis is a linked surface protein
      that behaves as an anchorless adhesin.
AB  - BACKGROUND: The pathogenic fungus Paracoccidioides brasiliensis is the agent of
      paracoccidioidomycosis (PCM). This is a pulmonary mycosis acquired by inhalation
      of fungal airborne propagules that can disseminate to several organs and tissues
      leading to a severe form of the disease. Adhesion and invasion to host cells are
      essential steps involved in the internalization and dissemination of pathogens.
      Inside the host, P. brasiliensis may use the glyoxylate cycle for intracellular
      survival. RESULTS: Here, we provide evidence that the malate synthase of P.
      brasiliensis (PbMLS) is located on the fungal cell surface, and is secreted.
      PbMLS was overexpressed in Escherichia coli, and polyclonal antibody was obtained
      against this protein. By using Confocal Laser Scanning Microscopy, PbMLS was
      detected in the cytoplasm and in the cell wall of the mother, but mainly of
      budding cells of the P. brasiliensis yeast phase. PbMLSr and its respective
      polyclonal antibody produced against this protein inhibited the interaction of P.
      brasiliensis with in vitro cultured epithelial cells A549. CONCLUSION: These
      observations indicated that cell wall-associated PbMLS could be mediating the
      binding of fungal cells to the host, thus contributing to the adhesion of fungus
      to host tissues and to the dissemination of infection, behaving as an anchorless
      adhesin.

PMID- 20034377
TI  - Ranges of control in the transcriptional regulation of Escherichia coli.
AB  - BACKGROUND: The positioning of genes in the genome is an important evolutionary
      degree of freedom for organizing gene regulation. Statistical properties of these
      distributions have been studied particularly in relation to the transcriptional
      regulatory network. The systematics of gene-gene distances then become important
      sources of information on the control, which different biological mechanisms
      exert on gene expression. RESULTS: Here we study a set of categories, which has
      to our knowledge not been analyzed before. We distinguish between genes that do
      not participate in the transcriptional regulatory network (i.e. that are
      according to current knowledge not producing transcription factors and do not
      possess binding sites for transcription factors in their regulatory region), and
      genes that via transcription factors either are regulated by or regulate other
      genes. We find that the two types of genes ("isolated" and "regulatory" genes)
      show a clear statistical repulsion and have different ranges of correlations. In
      particular we find that isolated genes have a preference for shorter intergenic
      distances. CONCLUSIONS: These findings support previous evidence from gene
      expression patterns for two distinct logical types of control, namely digital
      control (i.e. network-based control mediated by dedicated transcription factors)
      and analog control (i.e. control based on genome structure and mediated by
      neighborhood on the genome).

PMID- 20034378
TI  - Calculating the potential for within-flight transmission of influenza A (H1N1).
AB  - BACKGROUND: Clearly air travel, by transporting infectious individuals from one
      geographic location to another, significantly affects the rate of spread of
      influenza A (H1N1). However, the possibility of within-flight transmission of
      H1N1 has not been evaluated; although it is known that smallpox, measles,
      tuberculosis, SARS and seasonal influenza can be transmitted during commercial
      flights. Here we present the first quantitative risk assessment to assess the
      potential for within-flight transmission of H1N1. METHODS: We model airborne
      transmission of infectious viral particles of H1N1 within a Boeing 747 using
      methodology from the field of quantitative microbial risk assessment. RESULTS:
      The risk of catching H1N1 will essentially be confined to passengers travelling
      in the same cabin as the source case. Not surprisingly, we find that the longer
      the flight the greater the number of infections that can be expected. We
      calculate that H1N1, even during long flights, poses a low to moderate within
      flight transmission risk if the source case travels First Class. Specifically, 0
      1 infections could occur during a 5 hour flight, 1-3 during an 11 hour flight and
      2-5 during a 17 hour flight. However, within-flight transmission could be
      significant, particularly during long flights, if the source case travels in
      Economy Class. Specifically, two to five infections could occur during a 5 hour
      flight, 5-10 during an 11 hour flight and 7-17 during a 17 hour flight. If the
      aircraft is only partially loaded, under certain conditions more infections could
      occur in First Class than in Economy Class. During a 17 hour flight, a greater
      number of infections would occur in First Class than in Economy if the First
      Class Cabin is fully occupied, but Economy class is less than 30% full.
      CONCLUSIONS: Our results provide insights into the potential utility of air
      travel restrictions on controlling influenza pandemics in the winter of
      2009/2010. They show travel by one infectious individual, rather than causing a
      single outbreak of H1N1, could cause several simultaneous outbreaks. These
      results imply that, during a pandemic, quarantining passengers who travel in
      Economy on long-haul flights could potentially be an important control strategy.
      Notably, our results show that quarantining passengers who travel First Class
      would be unlikely to be an effective control strategy.

PMID- 20034379
TI  - Increased liver regeneration rate and decreased liver function after synchronous
      liver and colon resection in rats.
AB  - BACKGROUND: The surgical strategy for the treatment of colorectal cancer and
      synchronous liver metastases remains controversial. The aim of the present study
      was to investigate the effects of colonic resection on liver function and
      regeneration in a rat model. METHODS: Ninety-six Sprague-Dawley rats were block
      randomized into six groups: Group I had a laparotomy performed. Group II had 1 cm
      colon resected and anastomosed. Group III and V had 40% or 70% of the liver
      resected, respectively. Additionally Group IV and VI had 1 cm colon resected and
      anastomosed, respectively. Body weight was recorded on postoperative day 0, 3, 5
      and 7. Rats were sacrificed on postoperative day 7 by rapid collection of blood
      from the inferior vena cava, and endotoxin levels were measured. Remnant liver
      function was evaluated by means of branched amino acids to tyrosine ratio. Liver
      regeneration was calculated by (liver weight per 100 g of the body weight at
      sacrifice/preoperative projected liver weight per 100 g of the body weight) x
      100. RESULTS: The total number of complications was significantly higher in Group
      VI than Group I, III, IV, and V. Body weight and branched amino acids to tyrosine
      ratio were both significantly lower in rats that had simultaneous colonic and
      liver resection performed. Hepatic regeneration rate was significantly higher in
      the simultaneous colectomy group. Systemic endotoxin levels were unaffected by
      simultaneous colectomy on postoperative day 7. CONCLUSIONS: In our model
      morbidity seems to be related to the extent of hepatic resection. In rats
      undergoing liver resection, simultaneous colectomy induced a higher degree of
      hepatic regeneration rate. Body weight changes and branched amino acids to
      tyrosine ratio were negatively affected by simultaneous colectomy.

PMID- 20034380
TI  - Editorial: hypotheses about protein folding--the proteomic code and wonderfolds.
AB  - Theoretical biology journals can contribute in many ways to the progress of
      knowledge. They are particularly well-placed to encourage dialogue and debate
      about hypotheses addressing problematical areas of research. An online journal
      provides an especially useful forum for such debate because of the option of
      posting comments within days of the publication of a contentious article.

PMID- 20034381
TI  - Living healthier for longer: comparative effects of three heart-healthy behaviors
      on life expectancy with and without cardiovascular disease.
AB  - BACKGROUND: Non-smoking, having a normal weight and increased levels of physical
      activity are perhaps the three key factors for preventing cardiovascular disease
      (CVD). However, the relative effects of these factors on healthy longevity have
      not been well described. We aimed to calculate and compare the effects of non
      smoking, normal weight and physical activity in middle-aged populations on life
      expectancy with and without cardiovascular disease. METHODS: Using multi-state
      life tables and data from the Framingham Heart Study (n = 4634) we calculated the
      effects of three heart healthy behaviours among populations aged 50 years and
      over on life expectancy with and without cardiovascular disease. For the life
      table calculations, we used hazard ratios for 3 transitions (No CVD to CVD, no
      CVD to death, and CVD to death) by health behaviour category, and adjusted for
      age, sex, and potential confounders. RESULTS: High levels of physical activity,
      never smoking (men), and normal weight were each associated with 20-40% lower
      risks of developing CVD as compared to low physical activity, current smoking and
      obesity, respectively. Never smoking and high levels of physical activity reduced
      the risks of dying in those with and without a history of CVD, but normal weight
      did not. Never-smoking was associated with the largest gains in total life
      expectancy (4.3 years, men, 4.1 years, women) and CVD-free life expectancy (3.8
      and 3.4 years, respectively). High levels of physical activity and normal weight
      were associated with lesser gains in total life expectancy (3.5 years, men and
      3.4 years, women, and 1.3 years, men and 1.0 year women, respectively), and
      slightly lesser gains in CVD-free life expectancy (3.0 years, men and 3.1 years,
      women, and 3.1 years men and 2.9 years women, respectively). Normal weight was
      the only behaviour associated with a reduction in the number of years lived with
      CVD (1.8 years, men and 1.9 years, women). CONCLUSIONS: Achieving high levels of
      physical activity, normal weight, and never smoking, are effective ways to
      prevent cardiovascular disease and to extend total life expectancy and the number
      of years lived free of CVD. Increasing the prevalence of normal weight could
      further reduce the time spent with CVD in the population.

PMID- 20034382
TI  - False aneurysm of the interosseous artery and anterior interosseous syndrome--an
      unusual complication of penetrating injury of the forearm: a case report.
AB  - BACKGROUND: Palsies involving the anterior interosseous nerve (AIN) comprise less
      than 1% of all upper extremity nerve palsies. OBJECTIVES: This case highlights
      the potential vascular and neurological hazards of minimal penetrating injury of
      the proximal forearm and emphasizes the phenomenon of delayed presentation of
      vascular injuries following seemingly obscure penetrating wounds. CASE REPORT: We
      report a case of a 22-year-old male admitted for a minimal penetrating trauma of
      the proximal forearm that, some days later, developed an anterior interosseous
      syndrome. A Duplex study performed immediately after the trauma was normal.
      Further radiologic investigations i.e. a computer-tomographic-angiography (CTA)
      revealed a false aneurysm of the proximal portion of the interosseous artery
      (IA). Endovascular management was proposed but a spontaneous rupture dictated
      surgical revision with simple excision. Complete neurological recovery was
      documented at 4 months postoperatively. CONCLUSIONS/SUMMARY: After every
      penetrating injury of the proximal forearm we propose routinely a detailed
      neurological and vascular status and a CTA if Duplex evaluation is negative.

PMID- 20034383
TI  - Data mining of enzymes using specific peptides.
AB  - BACKGROUND: Predicting the function of a protein from its sequence is a long
      standing challenge of bioinformatic research, typically addressed using either
      sequence-similarity or sequence-motifs. We employ the novel motif method that
      consists of Specific Peptides (SPs) that are unique to specific branches of the
      Enzyme Commission (EC) functional classification. We devise the Data Mining of
      Enzymes (DME) methodology that allows for searching SPs on arbitrary proteins,
      determining from its sequence whether a protein is an enzyme and what the
      enzyme's EC classification is. RESULTS: We extract novel SP sets from Swiss-Prot
      enzyme data. Using a training set of July 2006, and test sets of July 2008, we
      find that the predictive power of SPs, both for true-positives (enzymes) and true
      negatives (non-enzymes), depends on the coverage length of all SP matches (the
      number of amino-acids matched on the protein sequence). DME is quite different
      from BLAST. Comparing the two on an enzyme test set of July 2008, we find that
      DME has lower recall. On the other hand, DME can provide predictions for proteins
      regarded by BLAST as having low homologies with known enzymes, thus supplying
      complementary information. We test our method on a set of proteins belonging to
      10 bacteria, dated July 2008, establishing the usefulness of the coverage-length
      cutoff to determine true-negatives. Moreover, sifting through our predictions we
      find that some of them have been substantiated by Swiss-Prot annotations by July
      2009. Finally we extract, for production purposes, a novel SP set trained on all
      Swiss-Prot enzymes as of July 2009. This new set increases considerably the
      recall of DME. The new SP set is being applied to three metagenomes: Sargasso Sea
      with over 1,000,000 proteins, producing predictions of over 220,000 enzymes, and
      two human gut metagenomes. The outcome of these analyses can be characterized by
      the enzymatic profile of the metagenomes, describing the relative numbers of
      enzymes observed for different EC categories. CONCLUSIONS: Employing SPs for
      predicting enzymatic activity of proteins works well once one utilizes coverage
      length criteria. In our analysis, L >or= 7 has led to highly accurate results.

PMID- 20034384
TI  - Effect of initiation-inhibition and handedness on the patterns of the P50 event
      related potential component: a low resolution electromagnetic tomography study.
AB  - BACKGROUND: Recent research recognizes the association between handedness,
      linguistic processes and cerebral networks subserving executive functioning, but
      the nature of this association remains unclear. Since the P50 event related
      potential (ERP) is considered to reflect thalamocortical processes in association
      with working memory (WM) operation the present study focuses on P50 patterns
      elicited during the performance of a linguistic related executive functioning
      test in right- and left-handers. METHODS: In 64 young adults with a high
      educational level (33 left-handed) the P50 event-related potential was recorded
      while performing the initiation and inhibition condition of a modified version of
      the Hayling Sentence Completion test adjusted to induce WM. The manual preference
      of the participants was evaluated with the use of the Edinburgh Handedness
      Inventory (EHI). RESULTS: P50 showed greater amplitudes in left- than in right
      handers, mainly in frontal leads, in the initiation condition. Reduced amplitudes
      in inhibition compared to initiation condition were observed in left-handers. Low
      Resolution Electromagnetic Tomography (LORETA) analysis showed lower frontal lobe
      activation in the inhibition than in the initiation condition in both right- and
      left-handers. Also, LORETA yielded that right-handers exhibited greater
      activation in the inhibition condition than left-handers. Additionally, LORETA
      showed assymetrical hemispheric activation patterns in right-handers, in contrast
      to symmetrical patterns observed in left-handers. Higher P50 amplitudes were
      recorded in right-hemisphere of right-handers in the initiation condition.
      CONCLUSION: Brain activation, especially the one closely related to
      thalamocortical function, elicited during WM operation involving initiation and
      inhibition processes appears to be related to handedness.

PMID- 20034385
TI  - Polymorphisms in gene encoding TRPV1-receptor involved in pain perception are
      unrelated to chronic pancreatitis.
AB  - BACKGROUND: The major clinical feature in chronic pancreatitis is pain, but the
      genetic basis of pancreatic pain in chronic pancreatitis is poorly understood.
      The transient receptor potential vanilloid receptor 1 (TRPV1) gene has been
      associated with pain perception, and genetic variations in TRPV1 may modify the
      presence and phenotype of chronic pancreatitis. The aim of our study was to
      investigate the genetic variation of TRPV1 in Dutch patients with chronic
      pancreatitis and healthy controls. METHODS: We genotyped 4 SNPs (rs222749,
      rs222747, rs224534 and rs8065080) in 228 chronic pancreatitis-patients and 207
      healthy controls by PCR, followed by restriction-fragment-length-polymorphism
      analysis and DNA sequencing. We generated 27 diplotypes and compared prevalence
      between patients and controls. RESULTS: There was no significant difference in
      allele frequency of the 4 TRPV1 gene SNPs in patients with chronic pancreatitis
      and healthy controls. Distribution of diplotypes was not statistically
      significantly different between patients and controls. CONCLUSION: TRPV1
      diplotypes are not associated with chronic pancreatitis.

PMID- 20034387
TI  - The use of inhaled corticosteroid in preschool wheezers: what's the point today?
AB  - AMONG THE PRESCHOOL CHILDREN WHO WHEEZE TWO DIFFERENT GROUPS CAN BE IDENTIFY:
      children who have a viral infection and those who respond to multiple triggers,
      such as exercise or allergens.To distinguish between these different phenotypes
      of wheezing, and consequently choose therapy represents a major challenge for
      pediatricians.Transient wheezers conditions do not improve with maintenance
      treatment with ICS. On the other hand they are definitely useful in children with
      wheeze/asthma.Increasing evidence is in favor of the potential role of
      leukotriene receptor antagonists in preschool children with recurrent
      wheezing.Oral steroid has been demonstrated not to be indicated to control acute
      wheezing, unless severe disease is expected in non-atopic children.The early
      phenotyping of preschool wheezers, upon which the appropriate treatment should be
      based, represents a challenging issue in the paediatric practice.

PMID- 20034386
TI  - Role of ADAM and ADAMTS metalloproteinases in airway diseases.
AB  - Lungs are exposed to the outside environment and therefore to toxic and
      infectious agents or allergens. This may lead to permanent activation of innate
      immune response elements. A Disintegrin And Metalloproteinases (ADAMs) and ADAMs
      with Thrombospondin motifs (ADAMTS) are proteinases closely related to Matrix
      Metalloproteinases (MMPs). These multifaceted molecules bear metalloproteinase
      and disintegrin domains endowing them with features of both proteinases and
      adhesion molecules. Proteinases of the ADAM family are associated to various
      physiological and pathological processes and display a wide spectrum of
      biological effects encompassing cell fusion, cell adhesion, "shedding process",
      cleavage of various substrates from the extracellular matrix, growth factors or
      cytokines... This review will focus on the putative roles of ADAM/ADAMTS
      proteinases in airway diseases such as asthma and COPD.

PMID- 20034388
TI  - Increased production of viral proteins by a 3'-LTR-deleted infectious clone of
      human T-cell leukemia virus type 1.
AB  - We previously reported that a full-length provirus of HTLV-1 was directly
      constructed from the HTLV-1-transformed cell line MT-2 using overlapping
      polymerase chain reaction (PCR) and cloned into a plasmid vector (pFL-MT2). 293T
      cells transfected with pFL-MT2 alone did not produce virus particles because
      there was no expression of the viral transactivator protein Tax, whereas cells
      transfected with pFL-MT2 plus a Tax expression vector produced virus-like
      particles. In the process of constructing the HTLV-1 provirus by overlapping PCR,
      we also constructed an incomplete molecular clone, in which the 3' long terminal
      repeat (LTR) was replaced with the endogenous human gene, which resulted in the
      expression of a tax gene shorter by 43 bp. This incomplete molecular clone alone
      expressed Tax and produced the viral protein in transfected cells. Various clones
      were then constructed with different lengths of the 3' LTR and lacking the
      reverse-direction TATA box. The clones contained over 113 bp of the 3' LTR, with
      no reverse-direction TATA box, which might express the full-length tax gene, and
      did not produce the viral antigen. These results suggest that Tax in which the C
      terminal portion is deleted is more strongly expressed than the wild-type protein
      and has transcriptional activity.

PMID- 20034389
TI  - Specialty choice in UK junior doctors: is psychiatry the least popular specialty
      for UK and international medical graduates?
AB  - BACKGROUND: In the UK and many other countries, many specialties have had
      longstanding problems with recruitment and have increasingly relied on
      international medical graduates to fill junior and senior posts. We aimed to
      determine what specialties were the most popular and desirable among candidates
      for training posts, and whether this differed by country of undergraduate
      training. METHODS: We conducted a database analysis of applications to
      Modernising Medical Careers for all training posts in England in 2008. Total
      number of applications (as an index of popularity) and applications per vacancy
      (as an index of desirability) were analysed for ten different specialties. We
      tested whether mean consultant incomes correlated with specialty choice. RESULTS:
      In, 2008, there were 80,949 applications for specialty training in England, of
      which 31,434 were UK graduates (39%). Among UK medical graduates, psychiatry was
      the sixth most popular specialty (999 applicants) out of 10 specialty groups,
      while it was fourth for international graduates (5,953 applicants). Among UK
      graduates, surgery (9.4 applicants per vacancy) and radiology (8.0) had the
      highest number of applicants per vacancy and paediatrics (1.2) and psychiatry
      (1.1) the lowest. Among international medical graduates, psychiatry had the
      fourth highest number of applicants per place (6.3). Specialty popularity for UK
      graduates was correlated with predicted income (p = 0.006). CONCLUSION: Based on
      the number of applicants per place, there was some consistency in the most
      popular specialties for both UK and international medical graduates, but there
      were differences in the popularity of psychiatry. With anticipated decreases in
      the number of new international medical graduates training in the UK, university
      departments and professional associations may need to review strategies to
      attract more UK medical graduates into certain specialties, particularly
      psychiatry and paediatrics.

PMID- 20034390
TI  - Sensitivity is not an intrinsic property of a diagnostic test: empirical evidence
      from histological diagnosis of Helicobacter pylori infection.
AB  - BACKGROUND: We aimed to provide empirical evidence of how spectrum effects can
      affect the sensitivity of histological assessment of Helicobacter pylori
      infection, which may contribute to explain the heterogeneity in prevalence
      estimates across populations with expectedly similar prevalence. METHODS: Cross
      sectional evaluation of dyspeptic subjects undergoing upper digestive endoscopy,
      including collection of biopsy specimens from the greater curvature of the antrum
      for assessment of H. pylori infection by histopathological study and polymerase
      chain reaction (PCR), from Portugal (n = 106) and Mozambique (n = 102) following
      the same standardized protocol. RESULTS: In the Portuguese sample the prevalence
      of infection was 95.3% by histological assessment and 98.1% by PCR. In the
      Mozambican sample the prevalence was 63.7% and 93.1%, respectively. Among those
      classified as infected by PCR, the sensitivity of histological assessment was
      96.2% among the Portuguese and 66.3% among the Mozambican. Among those testing
      positive by both methods, 5.0% of the Portuguese and 20.6% of the Mozambican had
      mild density of colonization. CONCLUSIONS: This study shows a lower sensitivity
      of histological assessment of H. pylori infection in Mozambican dyspeptic
      patients compared to the Portuguese, which may be explained by differences in the
      density of colonization, and may contribute to explain the heterogeneity in
      prevalence estimates across African settings.

PMID- 20034391
TI  - Quantitative mass spectrometry of TATA binding protein-containing complexes and
      subunit phosphorylations during the cell cycle.
AB  - BACKGROUND: Progression through the cell cycle is accompanied by tightly
      controlled regulation of transcription. On one hand, a subset of genes is
      expressed in a cell cycle-dependent manner. On the other hand, a general
      inhibition of transcription occurs during mitosis. Genetic and genome-wide
      studies suggest cell cycle regulation at the level of transcription initiation by
      protein complexes containing the common DNA-binding subunit TATA binding protein
      (TBP). TBP is a key player in regulating transcription by all three nuclear RNA
      polymerases. It forms at least four distinct protein complexes with TBP
      associated factors (TAFs): SL1, B-TFIID, TFIID, and TFIIIB. Some TAFs are known
      to remain associated with TBP during the cell cycle. Here we analyze all TAFs and
      their phosphorylation status during the cell cycle using a quantitative mass
      spectrometry approach. RESULTS: TBP protein complexes present in human cells at
      the G2/M and G1/S transitions were analyzed by combining affinity purification
      with quantitative mass spectrometry using stable isotope labeling with amino
      acids in cell culture (SILAC). Phosphorylations were mapped and quantified after
      enrichment of tryptic peptides by titanium dioxide. This revealed that subunit
      stoichiometries of TBP complexes remained intact, but their relative abundances
      in nuclear extracts changed during the cell cycle. Several novel phosphorylations
      were detected on subunits of the TBP complexes TFIID and SL1. G2/M-specific
      phosphorylations were detected on TAF1, TAF4, TAF7, and TAFI41/TAF1D, and G1/S
      specific dephosphorylations were detected on TAF3. Many phosphorylated residues
      were evolutionary conserved from human to zebrafish and/or drosophila, and were
      present in conserved regions suggesting important regulatory functions.
      CONCLUSIONS: This study provides the first quantitative proteomic analysis of
      human TBP containing protein complexes at the G2/M and G1/S transitions, and
      identifies new cell cycle-dependent phosphorylations on TAFs present in their
      protein complex. We speculate that phosphorylation of complex-specific subunits
      may be involved in regulating the activities of TBP protein complexes during the
      cell cycle.

PMID- 20034392
TI  - Next generation transcriptomes for next generation genomes using est2assembly.
AB  - BACKGROUND: The decreasing costs of capillary-based Sanger sequencing and next
      generation technologies, such as 454 pyrosequencing, have prompted an explosion
      of transcriptome projects in non-model species, where even shallow sequencing of
      transcriptomes can now be used to examine a range of research questions. This
      rapid growth in data has outstripped the ability of researchers working on non
      model species to analyze and mine transcriptome data efficiently. RESULTS: Here
      we present a semi-automated platform 'est2assembly' that processes raw sequence
      data from Sanger or 454 sequencing into a hybrid de-novo assembly, annotates it
      and produces GMOD compatible output, including a SeqFeature database suitable for
      GBrowse. Users are able to parameterize assembler variables, judge assembly
      quality and determine the optimal assembly for their specific needs. We used
      est2assembly to process Drosophila and Bicyclus public Sanger EST data and then
      compared them to published 454 data as well as eight new insect transcriptome
      collections. CONCLUSIONS: Analysis of such a wide variety of data allows us to
      understand how these new technologies can assist EST project design. We determine
      that assembler parameterization is as essential as standardized methods to judge
      the output of ESTs projects. Further, even shallow sequencing using 454 produces
      sufficient data to be of wide use to the community. est2assembly is an important
      tool to assist manual curation for gene models, an important resource in their
      own right but especially for species which are due to acquire a genome project
      using Next Generation Sequencing.

PMID- 20034393
TI  - Postmenopausal estrogen and progestin effects on the serum proteome.
AB  - BACKGROUND: Women's Health Initiative randomized trials of postmenopausal hormone
      therapy reported intervention effects on several clinical outcomes, with some
      important differences between estrogen alone and estrogen plus progestin. The
      biologic mechanisms underlying these effects, and these differences, have yet to
      be fully elucidated. METHODS: Baseline serum samples were compared with samples
      drawn 1 year later for 50 women assigned to active hormone therapy in both the
      estrogen-plus-progestin and estrogen-alone randomized trials, by applying an in
      depth proteomic discovery platform to serum pools from 10 women per pool.
      RESULTS: In total, 378 proteins were quantified in two or more of the 10 pooled
      serum comparisons, by using strict identification criteria. Of these, 169 (44.7%)
      showed evidence (nominal P < 0.05) of change in concentration between baseline
      and 1 year for one or both of estrogen-plus-progestin and estrogen-alone groups.
      Quantitative changes were highly correlated between the two hormone-therapy
      preparations. A total of 98 proteins had false discovery rates < 0.05 for change
      with estrogen plus progestin, compared with 94 for estrogen alone. Of these, 84
      had false discovery rates <0.05 for both preparations. The observed changes
      included multiple proteins relevant to coagulation, inflammation, immune
      response, metabolism, cell adhesion, growth factors, and osteogenesis. Evidence
      of differential changes also was noted between the hormone preparations, with the
      strongest evidence in growth factor and inflammation pathways. CONCLUSIONS: Serum
      proteomic analyses yielded a large number of proteins similarly affected by
      estrogen plus progestin and by estrogen alone and identified some proteins and
      pathways that appear to be differentially affected between the two hormone
      preparations; this may explain their distinct clinical effects.

PMID- 20034394
TI  - Mutagenesis of the transmembrane domain of the SARS coronavirus spike
      glycoprotein: refinement of the requirements for SARS coronavirus cell entry.
AB  - BACKGROUND: The spike protein (S) of SARS Coronavirus (SARS-CoV) mediates entry
      of the virus into target cells, including receptor binding and membrane fusion.
      Close to or in the viral membrane, the S protein contains three distinct motifs:
      a juxtamembrane aromatic part, a central highly hydrophobic stretch and a
      cysteine rich motif. Here, we investigate the role of aromatic and hydrophobic
      parts of S in the entry of SARS CoV and in cell-cell fusion. This was
      investigated using the previously described SARS pseudotyped particles system
      (SARSpp) and by fluorescence-based cell-cell fusion assays. RESULTS: Mutagenesis
      showed that the aromatic domain was crucial for SARSpp entry into cells, with a
      likely role in pore enlargement.Introduction of lysine residues in the
      hydrophobic stretch of S also resulted in a block of entry, suggesting the
      borders of the actual transmembrane domain. Surprisingly, replacement of a
      glycine residue, situated close to the aromatic domain, with a lysine residue was
      tolerated, whereas the introduction of a lysine adjacent to the glycine, was not.
      In a model, we propose that during fusion, the lateral flexibility of the
      transmembrane domain plays a critical role, as do the tryptophans and the
      cysteines. CONCLUSIONS: The aromatic domain plays a crucial role in the entry of
      SARS CoV into target cells. The positioning of the aromatic domain and the
      hydrophobic domain relative to each other is another essential characteristic of
      this membrane fusion process.

PMID- 20034395
TI  - Understanding the molecular basis of plant growth promotional effect of
      Pseudomonas fluorescens on rice through protein profiling.
AB  - BACKGROUND: Plant Growth Promoting Rhizobacteria (PGPR), Pseudomonas fluorescens
      strain KH-1 was found to exhibit plant growth promotional activity in rice under
      both in-vitro and in-vivo conditions. But the mechanism underlying such
      promotional activity of P. fluorescens is not yet understood clearly. In this
      study, efforts were made to elucidate the molecular responses of rice plants to
      P. fluorescens treatment through protein profiling. Two-dimensional
      polyacrylamide gel electrophoresis strategy was adopted to identify the PGPR
      responsive proteins and the differentially expressed proteins were analyzed by
      mass spectrometry. RESULTS: Priming of P. fluorescens, 23 different proteins
      found to be differentially expressed in rice leaf sheaths and MS analysis
      revealed the differential expression of some important proteins namely putative
      p23 co-chaperone, Thioredoxin h- rice, Ribulose-bisphosphate carboxylase large
      chain precursor, Nucleotide diPhosphate kinase, Proteosome sub unit protein and
      putative glutathione S-transferase protein. CONCLUSION: Functional analyses of
      the differential proteins were reported to be directly or indirectly involved in
      growth promotion in plants. Thus, this study confirms the primary role of PGPR
      strain KH-1 in rice plant growth promotion.

PMID- 20034396
TI  - The effects of age on skeletal muscle and the phosphocreatine energy system: can
      creatine supplementation help older adults.
AB  - Creatine supplementation has been found to significantly increase muscle strength
      and hypertrophy in young adults (</= 35 yr) particularly when consumed in
      conjunction with a resistance training regime. Literature examining the efficacy
      of creatine supplementation in older adults (55-82 yr) suggests creatine to
      promote muscle strength and hypertrophy to a greater extent than resistance
      training alone. The following is a review of literature reporting on the effects
      of creatine supplementation on intramuscular high energy phosphates, skeletal
      muscle morphology and quality of life in older adults. Results suggest creatine
      supplementation to be a safe, inexpensive and effective nutritional intervention,
      particularly when consumed in conjunction with a resistance training regime, for
      slowing the rate of muscle wasting that is associated with aging. Physicians
      should strongly consider advising older adults to supplement with creatine and to
      begin a resistance training regime in an effort to enhance skeletal muscle
      strength and hypertrophy, resulting in enhanced quality of life.

PMID- 20034397
TI  - Mucins in ovarian cancer diagnosis and therapy.
AB  - Ovarian cancer is the most lethal gynecologic malignancy and the five-year
      survival rate is only 35% after diagnosis. Epithelial ovarian cancer is a highly
      metastatic disease characterized by widespread peritoneal dissemination and
      ascites. The death incidences from ovarian cancer could be significantly lowered
      by developing new methods for the early diagnosis and treatment of this fatal
      disease. Several potential markers have been identified recently. However, mucins
      are the most promising markers for ovarian cancer diagnosis. Mucins are large
      extracellular, heavily glycosylated proteins and their aberrant expression has
      been implicated in the pathogenesis of a variety of cancers, including ovarian
      cancer. This review will summarize known facts about the pathological and
      molecular characteristics of ovarian cancer, the current status of ovarian cancer
      markers, as well as general information about mucins, the putative role of mucins
      in the progression of ovarian cancer and their potential use for the early
      diagnosis and treatment of this disease.

PMID- 20034398
TI  - American palm ethnomedicine: a meta-analysis.
AB  - BACKGROUND: Many recent papers have documented the phytochemical and
      pharmacological bases for the use of palms (Arecaceae) in ethnomedicine. Early
      publications were based almost entirely on interviews that solicited local
      knowledge. More recently, ethnobotanically guided searches for new medicinal
      plants have proven more successful than random sampling for identifying plants
      that contain biodynamic ingredients. However, limited laboratory time and the
      high cost of clinical trials make it difficult to test all potential medicinal
      plants in the search for new drug candidates. The purpose of this study was to
      summarize and analyze previous studies on the medicinal uses of American palms in
      order to narrow down the search for new palm-derived medicines. METHODS: Relevant
      literature was surveyed and data was extracted and organized into medicinal use
      categories. We focused on more recent literature than that considered in a review
      published 25 years ago. We included phytochemical and pharmacological research
      that explored the importance of American palms in ethnomedicine. RESULTS: Of 730
      species of American palms, we found evidence that 106 species had known medicinal
      uses, ranging from treatments for diabetes and leishmaniasis to prostatic
      hyperplasia. Thus, the number of American palm species with known uses had
      increased from 48 to 106 over the last quarter of a century. Furthermore, the
      pharmacological bases for many of the effects are now understood. CONCLUSIONS:
      Palms are important in American ethnomedicine. Some, like Serenoa repens and
      Roystonea regia, are the sources of drugs that have been approved for medicinal
      uses. In contrast, recent ethnopharmacological studies suggested that many of the
      reported uses of several other palms do not appear to have a strong physiological
      basis. This study has provided a useful assessment of the ethnobotanical and
      pharmacological data available on palms.

PMID- 20034399
TI  - Validation of a Chinese version of disease specific quality of life scale (HFS
      36) for hemifacial spasm in Taiwan.
AB  - BACKGROUND AND OBJECT: There was no Chinese questionnaire to evaluate the health
      related quality of life (HRQoL) in patients with hemifacial spasm (HFS). In this
      study, we aimed to validate a new disease-specific HRQoL scale for HFS (HFS-36)
      in Chinese version, and compared it to SF-36, a generic HRQoL scale. PATIENTS AND
      METHODS: The HFS-36 Chinese version was modified from English version of HFS-30,
      including subscales of mobility, activities of daily living (ADL), emotional well
      being, stigma, social support, cognition, bodily discomfort, and communication.
      All the items were scored on the 5-point scales, ranging from 0(never) to
      4(always). Patients with HFS were asked to answer HFS-36 and SF-36 questionnaires
      on the same day before and 6-8 weeks after Botulinum toxin (BTX) injections,
      respectively. The reliability and validity of HFS-36 scale were evaluated
      statistically. RESULTS: Totally, 103 patients (68 females; 35 males) were
      recruited in this study, with a mean age of 57.6 +/- 11.5 years and a mean
      duration of HFS for 7.6 +/- 5.8 years. The intra-class correlation (ICC) and
      Cronbach's alpha were over 0.7 in the majority of items. HFS-36 showed a good
      correlation to HFS severity before BTX treatment and a significant improvement of
      subscale scoring after BTX treatment. HFS-36 also had a significant correlation
      to the mental health of SF-36. CONCLUSIONS: The Chinese version of HFS-36
      demonstrated a good reliability and validity in subscales of motility, ADL,
      emotion well-being, stigma and bodily discomfort. The HRQoL was significantly
      improved after BTX treatment assessed by HFS-36 or SF-36. Compared to SF-36, HFS
      36 scale was more sensitive and specific to evaluate the HRQoL in HFS.

PMID- 20034400
TI  - In vitro suppression of the MMP-3 gene in normal and cytokine-treated human
      chondrosarcoma using small interfering RNA.
AB  - BACKGROUND: Matrix metalloproteinase (MMPs) synthesized and secreted from
      connective tissue cells have been thought to participate in degradation of the
      extracellular matrix. Increased MMPs activities that degrade proteoglycans have
      been measured in osteoarthritis cartilage. This study aims to suppress the
      expression of the MMP-3 gene in in vitro human chondrosarcoma using siRNA.
      METHODS: CELLS WERE CATEGORIZED INTO FOUR GROUPS: control (G.1); transfection
      solution treated (G.2); negative control siRNA treated (G.3); and MMP-3 siRNA
      treated (G.4). All four groups were further subdivided into two groups - treated
      and non-treated with IL-1beta- following culture for 48 and 72 h. We observed the
      effects of gene suppression according to cell morphology, glycosaminoglycan (GAG)
      and hyaluronan (HA) production, and gene expression by using real-time polymerase
      chain reaction (PCR). RESULTS: In IL-1beta treated cells the apoptosis rate in
      G.4 was found to be lower than in all other groups, while viability and mitotic
      rate were higher than in all other groups (p < 0.05). The production of GAG and
      HA in G.4 was significantly higher than the control group (p < 0.05). MMP-3 gene
      expression was downregulated significantly (p < 0.05). CONCLUSION: MMP-3 specific
      siRNA can inhibit the expression of MMP-3 in chondrosarcoma. This suggests that
      MMP-3 siRNA has the potential to be a useful preventive and therapeutic agent for
      osteoarthritis.

PMID- 20034401
TI  - Correlation of omega-3 levels in serum phospholipid from 2053 human blood samples
      with key fatty acid ratios.
AB  - BACKGROUND: This research was conducted to explore the relationships between the
      levels of omega-3 fatty acids in serum phospholipid and key fatty acid ratios
      including potential cut-offs for risk factor assessment with respect to coronary
      heart disease and fatal ischemic heart disease. METHODS: Blood samples (n = 2053)
      were obtained from free-living subjects in North America and processed for
      determining the levels of total fatty acids in serum phospholipid as omega-3
      fatty acids including EPA (eicosapentaenoic acid, 20:5 n-3) and DHA
      (docosahexaenoic acid, 22:6 n-3) by combined thin-layer and gas-liquid
      chromatographic analyses. The omega-3 levels were correlated with selected omega
      6: omega-3 ratios including AA (arachidonic acid, 20:4n-6): EPA and AA:(EPA+DHA).
      Based on previously-published levels of omega-3 fatty acids considered to be in a
      'lower risk' category for heart disease and related fatality, 'lower risk'
      categories for selected fatty acid ratios were estimated. RESULTS: Strong inverse
      correlations between the summed total of omega-3 fatty acids in serum
      phospholipid and all four ratios (omega-6:omega-3 (n-6:n-3), AA:EPA, AA:DHA, and
      AA:(EPA+DHA)) were found with the most potent correlation being with the omega
      6:omega-3 ratio (R(2) = 0.96). The strongest inverse relation for the EPA+DHA
      levels in serum phospholipid was found with the omega-6: omega-3 ratio (R(2) =
      0.94) followed closely by the AA:(EPA+DHA) ratio at R(2) = 0.88. It was estimated
      that 95% of the subjects would be in the 'lower risk' category for coronary heart
      disease (based on total omega-3 >or= 7.2%) with omega-6:omega-3 ratios <4.5 and
      AA:(EPA+DHA) ratios <1.4. The corresponding ratio cut-offs for a 'lower risk'
      category for fatal ischemic heart disease (EPA+DHA >or= 4.6%) were estimated at <
      5.8 and < 2.1, respectively. CONCLUSIONS: Strong inverse correlations between the
      levels of omega-3 fatty acids in serum (or plasma) phospholipid and omega-6:
      omega-3 ratios are apparent based on this large database of 2053 samples. Certain
      fatty acid ratios may aid in cardiovascular disease-related risk assessment
      if/when complete profiles are not available.

PMID- 20034402
TI  - Using patient and physician perspectives to develop a shared decision-making
      framework for colorectal cancer.
AB  - BACKGROUND: Colorectal cancer is the third leading cause of death from cancer
      worldwide with over 900,000 diagnoses and 639,000 deaths each year. Although
      shared decision making is broadly advocated as a mechanism by which to achieve
      patient-centred care, there has been little investigation of patient and
      physician shared decision-making preferences and practices or the outcomes
      associated with shared decision making in the context of colorectal cancer. AIM:
      The aim of this study is to determine patient and physician attitudes towards the
      use of shared decision making in the setting of colorectal cancer. METHODS:
      Standard principles of qualitative research will be used to sample and interview
      20 colorectal cancer patients in each of three tertiary care hospitals (n = 60)
      and 15 surgeons, radiation oncologists, and medical oncologists (n = 45)
      affiliated with cancer centres. The interview questions will be guided by a
      conceptual framework defining patient and physician factors that influence the
      shared decision-making process and associated outcomes in the setting of
      colorectal cancer. An inductive, grounded approach will be used by two
      investigators to independently analyze the interview transcripts. These
      investigators will meet to compare and achieve consensus on themes that will be
      tabulated to compare barriers, enablers, and outcomes of shared decision making
      by patient, physician, and contextual factors. DISCUSSION: This study is the
      first to examine both patient and physician perspectives on the use of shared
      decision making for colorectal cancer in North America or elsewhere. It will
      provide a framework that can be used to describe the shared decision-making
      process and its outcomes, and evaluate strategies to facilitate this process for
      patients with colorectal cancer.

PMID- 20034403
TI  - Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus,
      non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment.
AB  - BACKGROUND: The current epidemics of type 2 diabetes mellitus (T2DM), non
      alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent
      insulin-resistance diseases. Previous studies linked insulin resistance diseases
      to high fat diets or exposure to streptozotocin, a nitrosamine-related compound
      that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low
      level exposure to nitrosamines that are widely present in processed foods,
      amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and
      neurodegeneration. METHODS: Long Evans rat pups were treated with N
      nitrosodiethylamine (NDEA) by i.p. Injection, and upon weaning, they were fed
      with high fat (60%; HFD) or low fat (5%; LFD) chow for 6 weeks. Rats were
      evaluated for cognitive impairment, insulin resistance, and neurodegeneration
      using behavioral, biochemical, molecular, and histological methods. RESULTS: NDEA
      and HFD +/- NDEA caused T2DM, NASH, deficits in spatial learning, and
      neurodegeneration with hepatic and brain insulin and/or IGF resistance, and
      reductions in tau and choline acetyltransferase levels in the temporal lobe. In
      addition, pro-ceramide genes, which promote insulin resistance, were increased in
      livers and brains of rats exposed to NDEA, HFD, or both. In nearly all assays,
      the adverse effects of HFD+NDEA were worse than either treatment alone.
      CONCLUSIONS: Environmental and food contaminant exposures to low, sub-mutagenic
      levels of nitrosamines, together with chronic HFD feeding, function
      synergistically to promote major insulin resistance diseases including T2DM,
      NASH, and AD-type neurodegeneration. Steps to minimize human exposure to
      nitrosamines and consumption of high-fat content foods are needed to quell these
      costly and devastating epidemics.

PMID- 20034404
TI  - Genes targeted by the estrogen and progesterone receptors in the human
      endometrial cell lines HEC1A and RL95-2.
AB  - BACKGROUND: When the steroid hormones estrogen and progesterone bind to nuclear
      receptors, they have transcriptional impact on target genes in the human
      endometrium. These transcriptional changes have a critical function in preparing
      the endometrium for embryo implantation. METHODS: 382 genes were selected,
      differentially expressed in the receptive endometrium, to study their
      responsiveness of estrogen and progesterone. The endometrial cell lines HEC1A and
      RL95-2 were used as experimental models for the non-receptive and receptive
      endometrium, respectively. Putative targets for activated steroid hormone
      receptors were investigated by chromatin immunoprecipitation (ChIP) using
      receptor-specific antibodies. Promoter occupancy of the selected genes by steroid
      receptors was detected in ChIP-purified DNA by quantitative PCR (qPCR).
      Expression analysis by reverse transcriptase (RT)-PCR was used to further
      investigate hormone dependent mRNA expression regulation of a subset of genes.
      RESULTS: ChIP-qPCR analysis demonstrated that each steroid hormone receptor had
      distinct group of target genes in the endometrial cell lines. After estradiol
      treatment, expression of estrogen receptor target genes predominated in HEC1A
      cells (n = 137) compared to RL95-2 cells (n = 35). In contrast, expression of
      progesterone receptor target genes was higher in RL95-2 cells (n = 83) than in
      HEC1A cells (n = 7) after progesterone treatment. RT-PCR analysis of 20 genes
      demonstrated transcriptional changes after estradiol or progesterone treatment of
      the cell lines. CONCLUSIONS: Combined results from ChIP-qPCR and RT-PCR analysis
      showed different patterns of steroid hormone receptor occupancy at target genes,
      corresponding to activation or suppression of gene expression after hormone
      treatment of HEC1A and RL95-2 cell lines.

PMID- 20034405
TI  - Quantifying the impact of community quarantine on SARS transmission in Ontario:
      estimation of secondary case count difference and number needed to quarantine.
AB  - BACKGROUND: Community quarantine is controversial, and the decision to use and
      prepare for it should be informed by specific quantitative evidence of benefit.
      Case-study reports on 2002-2004 SARS outbreaks have discussed the role of
      quarantine in the community in transmission. However, this literature has not
      yielded quantitative estimates of the reduction in secondary cases attributable
      to quarantine as would be seen in other areas of health policy and cost
      effectiveness analysis. METHODS: Using data from the 2003 Ontario, Canada, SARS
      outbreak, two novel expressions for the impact of quarantine are presented.
      Secondary Case Count Difference (SCCD) reflects reduction in the average number
      of transmissions arising from a SARS case in quarantine, relative to not in
      quarantine, at onset of symptoms. SCCD was estimated using Poisson and negative
      binomial regression models (with identity link function) comparing the number of
      secondary cases to each index case for quarantine relative to non-quarantined
      index cases. The inverse of this statistic is proposed as the number needed to
      quarantine (NNQ) to prevent one additional secondary transmission. RESULTS: Our
      estimated SCCD was 0.133 fewer secondary cases per quarantined versus non
      quarantined index case; and a NNQ of 7.5 exposed individuals to be placed in
      community quarantine to prevent one additional case of transmission in the
      community. This analysis suggests quarantine can be an effective preventive
      measure, although these estimates lack statistical precision. CONCLUSIONS:
      Relative to other health policy areas, literature on quarantine tends to lack in
      quantitative expressions of effectiveness, or agreement on how best to report
      differences in outcomes attributable to control measure. We hope to further this
      discussion through presentation of means to calculate and express the impact of
      population control measures. The study of quarantine effectiveness presents
      several methodological and statistical challenges. Further research and
      discussion are needed to understand the costs and benefits of enacting
      quarantine, and this includes a discussion of how quantitative benefit should be
      communicated to decision-makers and the public, and evaluated.

PMID- 20034406
TI  - Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following
      pilocarpine-induced status epilepticus.
AB  - BACKGROUND: Neuroinflammation occurs after seizures and is implicated in
      epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction
      mediates monocyte infiltration in the neuroinflammatory cascade triggered in
      different brain pathologies. In this work CCR2 and CCL2 expression were examined
      following status epilepticus (SE) induced by pilocarpine injection. METHODS: SE
      was induced by pilocarpine injection. Control rats were injected with saline
      instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial
      cells was examined using imunohistochemical analyses. The number of CCR2 positive
      cells was determined using stereology probes in the hippocampus. CCL2 expression
      in the hippocampus was examined by molecular assay. RESULTS: Increased CCR2 was
      observed in the hippocampus after SE. Seizures also resulted in alterations to
      the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2
      was observed following SE. Microglial cells were more closely apposed to the CCR2
      labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2
      labeling in populations of hypertrophied astrocytes, especially in CA1 and
      dentate gyrus. These CCR2+ astroctytes were not observed in control rats.
      Examination of CCL2 expression showed that it was elevated in the hippocampus
      following SE. CONCLUSION: The data show that CCR2 and CCL2 are up-regulated in
      the hippocampus after pilocarpine-induced SE. Seizures also result in changes to
      CCR2 receptor expression in neurons and astrocytes. These changes might be
      involved in detrimental neuroplasticity and neuroinflammatory changes that occur
      following seizures.

PMID- 20034408
TI  - Evaporative drying of mouse spermatozoa.
AB  - Mouse spermatozoa can be evaporatively dried under a stream of nitrogen gas at
      ambient temperature and stored for 5 months at -80 degrees C. The method as it
      stands at present is available for practical use, although its value would be
      greatly increased if the spermatozoa could be stored at ambient temperature. The
      need for further research is stressed.

PMID- 20034407
TI  - Large-scale identification of odorant-binding proteins and chemosensory proteins
      from expressed sequence tags in insects.
AB  - BACKGROUND: Insect odorant binding proteins (OBPs) and chemosensory proteins
      (CSPs) play an important role in chemical communication of insects. Gene
      discovery of these proteins is a time-consuming task. In recent years, expressed
      sequence tags (ESTs) of many insect species have accumulated, thus providing a
      useful resource for gene discovery. RESULTS: We have developed a computational
      pipeline to identify OBP and CSP genes from insect ESTs. In total, 752,841 insect
      ESTs were examined from 54 species covering eight Orders of Insecta. From these
      ESTs, 142 OBPs and 177 CSPs were identified, of which 117 OBPs and 129 CSPs are
      new. The complete open reading frames (ORFs) of 88 OBPs and 123 CSPs were
      obtained by electronic elongation. We randomly chose 26 OBPs from eight species
      of insects, and 21 CSPs from four species for RT-PCR validation. Twenty two OBPs
      and 16 CSPs were confirmed by RT-PCR, proving the efficiency and reliability of
      the algorithm. Together with all family members obtained from the NCBI (OBPs) or
      the UniProtKB (CSPs), 850 OBPs and 237 CSPs were analyzed for their structural
      characteristics and evolutionary relationship. CONCLUSIONS: A large number of new
      OBPs and CSPs were found, providing the basis for deeper understanding of these
      proteins. In addition, the conserved motif and evolutionary analysis provide some
      new insights into the evolution of insect OBPs and CSPs. Motif pattern fine-tune
      the functions of OBPs and CSPs, leading to the minor difference in binding sex
      pheromone or plant volatiles in different insect Orders.

PMID- 20034409
TI  - Vitrification of human blastocysts: an update.
AB  - Transfer of blastocyst-stage embryos has been shown to increase pregnancy rates
      while allowing for improved selection of potentially viable embryos. At this late
      stage of development, lower numbers of embryos can be transferred, resulting in
      less high-order multiple pregnancies and increased implantation rates. Between
      January 2004 and February 2009, 8449 blastocysts from 2453 patients were
      vitrified. After 1398 vitrified embryo transfers (VET) of both day-5 and day-6
      blastocysts with a mean patient age of 34.6 +/- 5.0 years, the study centre has
      seen a survival rate of 96.3% (2730/2835), an implantation rate of 29.4% and a
      clinical pregnancy rate per VET of 42.8% (599 pregnancies/1398 warmed embryo
      transfers). After more than 5 years of vitrifying blastocysts, the perinatal
      outcome was, from 348 deliveries with vitrified blastocysts, the births of 431
      babies (202 boys and 229 girls). One of the benefits of blastocyst vitrification
      is that it can be undertaken on a more flexible basis by laboratory staff. Also,
      vitrification may allow individual blastocysts to be cryopreserved at their
      optimal stage of development and expansion.

PMID- 20034410
TI  - Vitrification of human mature oocytes in clinical practice.
AB  - Oocyte cryopreservation has long been the focus of unsuccessful efforts to
      perfect its clinical application. Lately, vitrification has been shown to provide
      high degrees of success by different research groups. This review attempts to
      address the efficiency of oocyte vitrification in clinical practice through an
      analysis of reports of IVF cycles in which embryo transfers have been conducted
      with vitrified metaphase-II human oocytes.

PMID- 20034411
TI  - Oocyte in-vitro maturation: BCL2 mRNA content in cumulus cells reflects oocyte
      competency.
AB  - BCL2-associated X protein (BAX) and B-cell leukaemia/lymphoma gene-2 (BCL2),
      which are, respectively, pro- and anti-apoptotic proteins of the BCL2 gene
      family, participate in the mitochondria-dependent apoptosis pathway. A
      correlation between low incidence of apoptosis in cumulus cells and oocyte
      maturation has previously been suggested in ovarian stimulation. However, little
      is known in unprimed ovaries. These authors have investigated whether BAX and
      BCL2 expression in cumulus cells affects the competency of in-vitro matured
      oocytes. We have studied 100 cumulus-oocyte-complexes (COC) recovered from
      unprimed ovaries of 13 women diagnosed with polycystic ovary syndrome (PCOS) and
      undergoing in-vitro maturation (IVM) with their informed consent. COC were
      matured for 24 h in a specific maturation medium and the cumulus was stripped
      from the oocyte. BAX and BCL2 mRNA content was measured in each COC using real
      time polymerase chain reaction. We found that BCL2 mRNA expression was
      significantly higher in cumulus cells associated with mature oocytes than those
      associated with immature oocytes while BAX mRNA concentrations did not vary in
      cumulus cells. Regarding fertilization, higher BCL2 mRNA content was found in
      cumulus cells enclosing fertilized oocytes (0.140 versus 0.075; P = 0.03). These
      results suggest that BCL2 expression is strongly associated with the ability of
      oocytes to complete nuclear maturation and to be fertilized.

PMID- 20034412
TI  - Characterization of human PGD blastocysts with unbalanced chromosomal
      translocations and human embryonic stem cell line derivation?
AB  - Novel embryonic stem cell lines derived from embryos carrying structural
      chromosomal abnormalities obtained after preimplantation genetic diagnosis (PGD)
      are of interest to study in terms of the influence of abnormalities on further
      development. A total of 22 unbalanced blastocysts obtained after PGD were
      analysed for structural chromosomal defects. Morphological description and
      chromosomal status of these blastocysts was established and they were used to
      derive human embryonic stem cell (ESC) lines. An outgrowth of cells was observed
      for six blastocysts (6/22; 27%). For two blastocysts, the exact morphology was
      unknown since they were at early stage, and for four blastocysts, the inner cell
      mass was clearly visible. Fifteen blastocysts carried an unbalanced chromosomal
      defect linked to a reciprocal translocation, resulting in a positive outgrowth of
      cells for five blastocysts. One human ESC line was obtained from a blastocyst
      carrying a partial chromosome-21 monosomy and a partial chromosome-1 trisomy. Six
      blastocysts carried an unbalanced chromosomal defect linked to a Robertsonian
      translocation, and one showed a positive outgrowth of cells. One blastocyst
      carried an unbalanced chromosomal defect linked to an insertion and no outgrowth
      was observed. The efficiency of deriving human ESC lines with constitutional
      chromosomal disorders was low and probably depends on the initial morphological
      aspect of the blastocysts and/or the type of the chromosomal disorders.

PMID- 20034413
TI  - What should be the first-line treatment for unexplained infertility in women over
      40 years of age - ovulation induction and IUI, or IVF?
AB  - The tendency to postpone childbearing in developed countries and the relatively
      high rate of infertility in older women contribute to an increase in the portion
      of women aged 40 years and older opting for infertility treatments. The main
      factor for infertility in this group is oocyte senescence, but since this process
      does not have a specific diagnosis many of those will be classified as having
      'unexplained infertility'. The efficacy of the traditional clinical approach for
      'unexplained infertility' in older women is questionable. Reviewing the current
      literature, clomiphene citrate seems to be inefficient in this group of patients,
      while delivery rates of gonadotrophins and intrauterine insemination cycles are
      less than 5%. Although low in absolute terms, IVF is more efficient. The chance
      for delivery, however, diminishes with each year of age above 40. Therefore,
      after a short trial of gonadotrophins and intrauterine insemination, women aged
      40-41 years should be quickly referred to IVF. At an older age, IVF is the
      primary treatment option.

PMID- 20034414
TI  - Reproductive efficiency of women over the age of 40 and the low risk of multiple
      pregnancies.
AB  - Infertile patients over the age of 40 are generally considered to have a low
      chance of success with assisted cycles despite high numbers of embryos
      transferred. The risk of multiple pregnancy in this group of patients is not well
      established. The present study determined the rate of embryos that fail to
      produce a live birth and the rate of multiple pregnancies in a cohort of women
      over the age of 40 undergoing IVF/intracytoplasmic sperm injection cycles,
      utilizing Society for Assisted Reproductive Technology reported cycle outcomes
      from national summaries as well as from two university-based IVF centres. The
      rate of embryo wastage for women over the age of 40 is approximately 95% and
      these women have a correspondingly low rate of multiple pregnancy per cycle
      started (2.5% and 1.6% for women aged 41-42 years and 43-44 years, respectively).
      These data underscore the low reproductive efficiency of oocytes in women over
      the age of 40 and the very low probability of a multiple-gestation live birth
      despite the high number of embryos transferred. This information is an important
      additional counselling tool at the time of embryo transfer in this group of
      patients.

PMID- 20034415
TI  - Should luteal phase support be introduced in ovarian stimulation/IUI programmes?
      An evidence-based review.
AB  - World-wide, intrauterine insemination (IUI) is still one of the most applied
      techniques to enhance the probability of conception in couples with longstanding
      subfertility. The outcome of this treatment option depends on many confounding
      factors. One of the confounding factors receiving little attention is the quality
      of the luteal phase. From IVF studies, it is known that ovarian stimulation
      causes luteal phase deficiency. Based on the best available evidence, this short
      review summarizes the indications for mild ovarian stimulation combined with IUI
      and the optimal stimulation programme. While it has been established that
      stimulated IVF/intracytoplasmic sperm injection cycles have deficient luteal
      phases, the question remains whether the quality of the luteal phase when only
      two or three corpora lutea are present (as is the case in stimulated IUI cycles)
      is impaired as well. There are too few large non-IVF trials studying luteal phase
      quality to answer this question. Recently a randomized trial has been published
      that investigated luteal phase support in an IUI programme. This study is
      discussed in detail. It is recommended to apply luteal phase support in
      stimulated IUI cycles only when proven costeffective. Further trials are
      mandatory to investigate both endometrial and hormonal profile changes in the
      luteal phase after mild ovarian stimulation, and the cost-effectiveness of luteal
      support in IUI programmes.

PMID- 20034416
TI  - Luteal-phase endocrinology.
AB  - The corpus luteum is formed from the pre-ovulatory follicle under the action of
      the mid-cycle LH surge. LH is the main luteotrophic hormone in women controlling
      luteal structure and function during the normal menstrual cycle. Local factors,
      however, including progesterone are also involved. If conception does not take
      place, luteolysis occurs as a physiological apoptotic process. Human chorionic
      gonadotrophin, secreted after implantation, is able to rescue the corpus luteum
      and extend its lifespan. In ovulation-induction cycles, the negative feedback
      effect of the ovarian steroids on the pituitary is markedly potentiated, leading
      to the suppression of endogenous LH secretion during the whole menstrual cycle.
      The marked suppression of LH secretion disrupts corpus luteum function regardless
      of the treatment regimen.

PMID- 20034417
TI  - The luteal phase after 3 decades of IVF: what do we know?
AB  - The luteal phases of all stimulated IVF cycles are abnormal. The main cause of
      the luteal phase defect (LPD) observed in stimulated IVF cycles is related to the
      multifollicular development achieved during ovarian stimulation. This may be
      related to the supra-physiological concentrations of steroids secreted by a high
      number of corpora lutea during the early luteal phase, which directly inhibit LH
      release via negative feedback actions at the hypothalamic-pituary axis level,
      rather than a central pituitary cause or steroidogenic abnormality in the corpus
      luteum. To correct the LPD in stimulated IVF cycles, human chorionic
      gonadotrophin (HCG) or progesterone can be administered. HCG is associated with a
      greater risk of ovarian hyperstimulation syndrome. Natural micronized
      progesterone is not efficient if taken orally. Vaginal and intramuscular
      progesterone do have comparable implantation, clinical pregnancy and delivery
      rates. However, because of severe side effects, intramuscular progesterone
      administration should be avoided.

PMID- 20034418
TI  - Vitrification in assisted reproduction: myths, mistakes, disbeliefs and
      confusion.
AB  - The purpose of this work is to update embryologists and clinicians on different
      approaches in human oocyte and embryo cryopreservation, by clarifying some
      misunderstandings and explaining the underlying reasons for controversial
      opinions. The work is based on literature review and critical analysis of
      published papers or conference abstracts during the last 24 years, with special
      focus on the last 3 years. Due to the latest advancements in techniques,
      cryopreservation now offers new perspectives along with solutions to many
      demanding problems, and has developed from a backup procedure to a successful
      alternative that is an indispensable constituent of assisted reproductive
      techniques. However, this progress is not free from controversies, at some points
      is rather serendipitous, and many factors, including human ones, hamper the
      selection and widespread application of the most efficient technique for the
      given task. A better understanding of the basic features of the two rival
      approaches (slow-rate freezing and vitrification), a clarification of terms and
      technical details, and a balanced, pragmatic evaluation of possible risks and
      potential, or definite, gains are required to accelerate advancement.
      Alternatively, the increasing flow of patients to the few assisted reproduction
      clinics and countries that are highly successful in this field will enforce the
      required changes in methodology and mentality worldwide.

PMID- 20034419
TI  - Impact of developmental stage at cryopreservation and transfer on clinical
      outcome of frozen embryo cycles.
AB  - Although several early IVF successes were achieved after transferring fully
      formed blastocysts, the majority of embryos replaced worldwide over the past 30
      years have been at the cleavage stage. The programme at this study centre has
      previously found that delaying an embryo transfer to day 5 can reduce the chance
      for a high-order multiple gestation without compromising the pregnancy rate
      because fewer embryos can be replaced. To evaluate the impact of transfer day and
      embryonic stage at cryopreservation on cycle outcome, 6069 fresh and 706 frozen
      transfers from 2000-2006 performed at this study centre were retrospectively
      analysed. Approximately half of the fresh transfers were performed on day 3, with
      a shift to day-5 transfer over the study period with no change in
      cryopreservation incidence. Implantation, clinical pregnancy and live birth rates
      were significantly higher following day-5 transfer. When frozen-thawed embryos (2
      cell to day-6 blastocysts) were transferred, acceptable pregnancy and live birth
      rates were achieved at all stages but thawed embryos transferred as day-5
      blastocysts generated consistently higher clinical pregnancy and live birth
      rates. Transfer of embryos frozen on day 6 had the highest miscarriage and lowest
      live birth rates. Barring government regulation, an IVF programme's day for
      cryopreservation generally depends on its management of and success with fresh
      embryo transfer.

PMID- 20034420
TI  - Ultrastructural markers of quality in human mature oocytes vitrified using
      cryoleaf and cryoloop.
AB  - This study describes and compares the possible effects of vitrification on the
      ultrastructural morphology of 20 human mature oocytes vitrified using two
      different supports, cryoleaf (n = 10) and cryoloop (n = 10). Fresh human mature
      oocytes (n = 15) were used as controls. Fresh and vitrified-warmed oocytes
      appeared rounded, with a homogeneous cytoplasm, an intact oolemma and a
      continuous zona pellucida. Sparse microvacuolization was only occasionally
      detected in fresh and vitrified-warmed oocytes, to the same extent. About 50% of
      the vitrified oocytes contained atypical, small and slender mitochondria-smooth
      endoplasmic reticulum aggregates, whereas a non-homogeneous microvillar pattern
      was observable in only 30% of the oocytes subjected to vitrification, regardless
      of the support utilized. Cortical granule content appeared generally reduced
      after vitrification, but cryoleaf-supported oocytes contained more cortical
      granules than cryoloop-supported oocytes (P < 0.05). Thus good overall
      preservation and virtual absence of cytoplasmic vacuolization seem to be the most
      relevant markers of quality in vitrified-warmed oocytes, using either support. In
      addition, cryoleaf-supported oocytes retained a higher number of cortical
      granules than cryoloop-supported oocytes. The variety of ultrastructural
      alterations recorded emphasizes the need for further studies aimed at assessing
      the actual tolerance of human oocytes to vitrification.

PMID- 20034421
TI  - Vitrification may increase the rate of chromosome misalignment in the metaphase
      II spindle of human mature oocytes.
AB  - The metaphase II (MII) spindle of the human oocyte may be damaged by
      cryopreservation. High performance confocal microscopy was used to assess meiotic
      spindle and chromosome organization in oocytes after vitrification by the
      cryoleaf system. Three hours after retrieval, donor mature oocytes were fixed or
      vitrified. Vitrification was performed by equilibration in 7.5% ethylene glycol
      (EG) and 7.5% dimethylsulphoxide (DMSO), transfer to 15% EG, 15% DMSO and 0.5
      mol/l sucrose, and loading onto cryoleaf strips. Tubulin staining was found in
      all survived vitrified-warmed oocytes, the majority (62.8%) of which displayed a
      bipolar spindle. A normal bipolar spindle configuration and equatorial chromosome
      alignment was observed only in a part of vitrified-warmed oocytes (32.6%). This
      frequency was significantly lower in comparison to fresh oocytes (59.1%). In
      another fraction of vitrified-warmed oocytes (30.2%), spindle bipolarity was
      associated to one or more non-aligned scattered chromosomes that often appeared
      tenuously associated with the lateral microtubules of the spindle. Furthermore,
      in cryopreserved oocytes with a bipolar spindle, a significantly increased pole
      to-pole distance (14.9 +/- 2.3 microm) was found in comparison to the fresh
      control (12.4 +/- 2.6 microm) (P = 0.001). Therefore, under the conditions
      tested, vitrified-warmed oocytes maintain a MII spindle with a bipolar
      organization. However, chromosome alignment appears to be partly compromised.

PMID- 20034422
TI  - Sperm-hyaluronan-binding assay: clinical value in conventional IVF under Italian
      law.
AB  - Hyaluronan has recently been employed in the development of a commercial
      diagnostic kit for assessing sperm maturity, the so-called sperm-hyaluronan
      binding assay (HBA). The aim of this study was to evaluate the usefulness of this
      test, in addition to routine semen analysis, to identify patients with poor
      reproductive prognosis in conventional IVF. Furthermore, the ability of
      hyaluronan to select spermatozoa with low DNA fragmentation was investigated. A
      total of 60 IVF patients were analysed with regard to reproductive outcome, sperm
      parameters, HBA score and sperm DNA fragmentation. The DNA fragmentation analysis
      was performed using the terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labelling assay on the total sperm population and on the hyaluronan-bound
      spermatozoa obtained from the same samples. No relationship between hyaluronan
      binding and fertilization, cleavage, good-quality embryos, implantation, clinical
      pregnancy, miscarriages and biochemical pregnancy rates was found. Otherwise,
      correlations between spermatozoa hyaluronan binding and morphology (P < 0.01) and
      a significant difference between DNA fragmentation of the total sperm population
      and DNA fragmentation of the hyaluronan-bound spermatozoa (P = 0.029) were found.
      The results underline the ability of hyaluronan to select spermatozoa with higher
      DNA integrity and morphology. Nevertheless, the clinical value of the HBA in the
      management of male infertility seems to be limited.

PMID- 20034423
TI  - Impact of intracytoplasmic morphologically selected sperm injection on assisted
      reproduction outcome: a review.
AB  - To date, several publications have focused their attention on a new method for
      observing spermatozoa called 'motile sperm organelle morphology examination'
      (MSOME), which enables the evaluation of the fine nuclear morphology of motile
      spermatozoa in real time at high magnification (>x6000). As a consequence, a new
      microinjection procedure called intracytoplasmic morphologically selected sperm
      injection (IMSI) has been developed. The aim of the present work is therefore to
      evaluate the efficacy of the IMSI technique in the light of the current
      literature, focusing attention on the potential clinical application of the
      selection of strictly morphologically normal spermatozoa in patients undergoing
      conventional intracytoplasmic sperm injection treatments. In addition, a brief
      analysis of preliminary data regarding the relationship between IMSI and assisted
      reproduction treatment outcome is presented.

PMID- 20034424
TI  - Role of Oct-4 during acquisition of developmental competence in mouse oocyte.
AB  - Knowledge of what determines the developmental competence of oocytes during
      folliculogenesis is poor. This review, through the analysis of the expression
      profile of developmentally competent or incompetent mouse oocytes, summarizes the
      results of recent studies showing that the Oct-4 transcription factor regulating
      the expression of Stella and Foxj2 at the Nanog locus could play a pivotal role
      in the establishment of the oocyte's developmental competence.

PMID- 20034425
TI  - AALAS Journals Reader Survey: survey conducted from April 16 to May 1, 2009
      survey--results reported to AALAS on May 1, 2009.

PMID- 20034427
TI  - Using ultrasonography to define fetal-maternal relationships: moving from humans
      to mice.
AB  - Ultrasound scanning is a noninvasive, accurate, and cost-effective method to
      create images of the female reproductive tract clinically and in research.
      Ultrasonography is particularly valuable for studying the dynamic relationships
      among mother, placenta, and fetus during pregnancy because this modality does not
      disturb the ongoing course of gestation. Importantly, the complex vascular
      changes in the mother induced by pregnancy and the vascular system generated to
      support placental function can be assessed quantitatively and functionally by
      ultrasonography. Many mouse models are available that address aspects of human
      placental function and dysfunction, but high-quality microultrasound technology
      suitable for use in pregnant mice has become widely available only recently. This
      technical advance now enables real-time recording of maternal-fetal interactions
      in pregnant rodents. The ability to perform microultrasonic analyses of
      parameters such as uterine arterial remodeling, hemodynamic changes, placental
      development, and fetal growth in mice now permits research that uses the same
      imaging platform as that for human patients. This capability will enhance the
      translation of information derived from rodent studies to the clinic.

PMID- 20034426
TI  - Acute phase response in animals: a review.
AB  - The acute phase response is a complex systemic early-defense system activated by
      trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it
      serves as a core of the innate immune response involving physical and molecular
      barriers and responses that serve to prevent infection, clear potential
      pathogens, initiate inflammatory processes, and contribute to resolution and the
      healing process. Acute phase proteins, an integral part of the acute phase
      response, have been a focus of many applications in human diagnostic medicine and
      recently have been identified in common animal species. Potential applications to
      diagnosis, prognosis, assessment of animal health, and laboratory animal welfare
      are readily apparent.

PMID- 20034428
TI  - The effect of Helicobacter hepaticus infection on immune responses specific to
      herpes simplex virus type 1 and characteristics of dendritic cells.
AB  - Infection of mice with Helicobacter hepaticus is common in research colonies, yet
      little is known about how this persistent infection affects immunologic research.
      The goal of this study was to determine whether H. hepaticus infection status can
      modulate immune responses specific to herpes simplex virus type 1 (HSV1) and the
      phenotypic and functional characteristics of dendritic cells (DC) of mice. We
      compared virus-specific antibody and T cell-mediated responses in H. hepaticus
      infected and noninfected mice that were inoculated intranasally with HSV1. The
      effect of H. hepaticus on the HSV1-specific antibody and T cell-mediated immune
      responses in superficial cervical and tracheobronchal lymph nodes (LN) did not
      reach statistical significance. Surface expression of the maturation-associated
      markers CD40, CD80, CD86, and MHC II and percentages of IL12p40- and TNFalpha
      producing DC from spleen and colic LN in H. hepaticus-infected mice and
      noninfected mice were measured in separate experiments. Expression of CD40, CD86,
      and MHC II and percentages of IL12p40- and TNFalpha-producing DC from colic LN
      were decreased in H. hepaticus-infected mice. In contrast, H. hepaticus infection
      did not reduce the expression of these molecules by splenic DC. Expression of
      CD40, CD80, CD86, and MHC II on splenic DC from H. hepaticus-infected mice was
      increased after in vitro lipopolysaccharide stimulation. These results indicate
      that H. hepaticus infection can influence the results of immunologic assays in
      mice and support the use of H. hepaticus-free mice in immunologic research.

PMID- 20034430
TI  - A mouse surgical model for metastatic ovarian granulosa cell tumor.
AB  - We recently described a genetically engineered mouse model that develops ovarian
      granulosa cell tumors (GCTs) that mimic many aspects of the advanced human
      disease, including distant dissemination. However, because the primary tumors
      killed their hosts before metastases were able to form, the use of these mice to
      study metastatic disease required the development of a simple, reliable, and
      humane surgical protocol for the excision of large GCTs from debilitated mice.
      Here we describe a protocol involving multimodal anesthesia, tumor removal
      through ventral midline celiotomy and perioperative fluid therapy, and analgesia
      that led to the postoperative survival of more than 90% of mice, despite the
      removal of tumors representing as much as 10% of the animal's body weight.
      Intraabdominal recurrence of the GCT did not occur in surviving animals, but most
      developed pulmonary or adrenal metastases (or both) by 12 wk after surgery. We
      propose that this mouse model of metastatic GCT will serve as a useful
      preclinical model for the development of novel treatment modalities and
      diagnostic techniques. Furthermore, our results delineate anesthetic and surgical
      principles for the removal of large abdominal tumors from mice that will be
      applicable to other models of human cancers.

PMID- 20034429
TI  - Mutational insertion of a ROSA26-EGFP transgene leads to defects in
      spermiogenesis and male infertility in mice.
AB  - Pronuclear injection has been a successful strategy for generating genetically
      engineered mouse models to better understand the functionality of genes. A
      characteristic of pronuclear injection is that random integration of the
      transgene into the genome can disturb a functional gene and result in a phenotype
      unrelated to the transgene itself. In this study, we have characterized a mouse
      model containing an insertional mutation that, in the homozygous state, severely
      affects spermatogenesis as characterized by lack of sperm motility and acrosomal
      aplasia. Whereas homozygous female mice had normal fertility, male mice
      homozygous for the insertional mutation were unable to produce pups by natural
      mating with either homozygous or wild-type female mice. No fertilized embryos
      were produced by matings to homozygous male mice, and no sperm were present in
      the reproductive tract of mated female mice. Spermatozoa isolated from homozygous
      male mice exhibited head and midpiece defects, but no major defects in the
      principal piece of these sperm. Histologic examination and immunohistochemical
      staining of the testes revealed vacuolar degeneration of Sertoli cells and loss
      of structural seminiferous tubule integrity and organization, indicating that
      spermatogenesis is severely affected in this mouse model. Although the males are
      always infertile, the severity of the histologic and sperm morphologic defects
      appeared to be age-related.

PMID- 20034431
TI  - Paeoniflorin prevents diabetic nephropathy in rats.
AB  - The aim of this study was to test the hypothesis that paeoniflorin prevents the
      progression of diabetic nephropathy by modulating the inflammatory process.
      Sprague-Dawley rats were divided into 5 groups: nondiabetic control rats;
      untreated diabetic model (DM) rats; and DM rats treated with 5, 10, or 20 mg/kg
      paeoniflorin in drinking water once daily. Rats received a single intravenous
      injection of streptozotocin to induce diabetes; 9 wk after injection, rats began
      the 8-wk daily paeoniflorin treatment regimen. Compared with that of nonDM
      controls, the urinary albumin:creatinine ratio was increased significantly in
      untreated DM rats; this ratio was decreased in DM rats treated with 5, 10, or 20
      mg/kg paeoniflorin compared with that of untreated DM rats. In addition,
      paeoniflorin treatment effectively suppressed glomerular hypertrophy; blood
      glucose; the expression of transforming growth factor beta, type IV collagen, and
      intercellular adhesion molecule 1; and renal infiltration of macrophages compared
      with levels in untreated DM rats. Furthermore, renal nuclear factor kappaB
      activity was increased in untreated but not paeoniflorin-treated DM rats. In
      conclusion, our data suggest that the preventive effects of paeoniflorin may be
      mediated by its antiinflammatory actions.

PMID- 20034432
TI  - Ribonucleotide reductase inhibitors reduce atherosclerosis in a double-injury
      rabbit model.
AB  - Atheroproliferative disorders such as atherosclerosis are an important health
      problem and one of the leading causes of morbidity and mortality in the United
      States. Minimally invasive therapeutic procedures, including angioplasty with
      stent deployment, are used frequently for obstructive coronary artery disease.
      However, restenosis, a proliferative vascular response, is a common sequela to
      this procedure. The current study investigated the effect of inhibiting
      ribonucleotide reductase (RR), an enzyme necessary for cellular proliferation, in
      an attempt to ameliorate the proliferative response. Two RR inhibitors, didox and
      hydroxyurea, were chosen for their potent antiproliferative properties. Studies
      were carried out by using a double-injury rabbit model, in which endothelial
      denudation was followed by the administration of a high-fat diet. At 4 wk after
      initial endothelial denudation, the developing atherosclerotic lesion was
      subjected to transluminal balloon dilation to simulate clinical intervention with
      percutaneous transluminal angioplasty. The degree of restenosis and
      atheroproliferation was assessed at 8 wk. Histologic evaluation of the lesion
      demonstrated that treatment with didox and hydroxyurea significantly decreased
      lesion area and lumen loss. These results suggest that RR inhibition may be an
      effective new tool for the treatment of atheroproliferative disorders.

PMID- 20034433
TI  - Using multidetector computed tomography in a swine model to assess the effects of
      sublingual nitroglycerin and intravenous adenosine on epicardial coronary
      arteries.
AB  - This study examines the effects of intravenous infusion of adenosine and
      sublingual nitroglycerin on coronary angiograms obtained by current-generation
      multidetector computed tomography. We assessed coronary vasodilation at baseline
      and after intravenous adenosine (140 microg/kg/min) or sublingual nitroglycerin
      spray (800 microg) in 7 female swine (weight, 40.9 +/- 1.4 kg) by using
      electrocardiogram-gated coronary angiography with a 64-detector scanner (rotation
      time, 400 ms; 120kV; 400 mA) and intravenous contrast (300 mg/mL iohexol, 4.5
      mL/s, 2 mL/kg). Cross-sectional areas of segments in the left anterior
      descending, circumflex, and right coronary arteries were evaluated in oblique
      orthogonal views. Images were acquired at an average heart rate of 73 +/- 11
      beats per minute. Changes in aortic pressure were not significant with
      nitroglycerin but decreased (approximately 10%) with adenosine. Of the 76
      segments analyzed (baseline range, 2 to 39 mm2), 1 distal segment could not be
      assessed after adenosine. Segment cross-sectional area increased by 11.3% with
      nitroglycerin but decreased by 9.6% during adenosine infusion. The results of the
      present study are consistent with the practice of using sublingual nitroglycerin
      to enhance visualization of epicardial vessels and suggest that intravenous
      adenosine may hinder coronary artery visualization. This study is the first
      repeated-measures electrocardiogram-gated CT evaluation to use the same imaging
      technology to assess changes in coronary cross-sectional area before and after
      treatment with a vasodilator. The nitroglycerin-associated changes in our swine
      model were modest in comparison with previously reported human studies.

PMID- 20034434
TI  - Comparative analyses of single-nucleotide polymorphisms in the TNF promoter
      region provide further validation for the vervet monkey model of obesity.
AB  - Tumor necrosis factor is a cytokine that plays critical roles in inflammation,
      the innate immune response, and a variety of other physiologic and
      pathophysiologic processes. In addition, TNF has recently been shown to mediate
      an intersection of chronic, low-grade inflammation and concurrent metabolic
      dysregulation associated with obesity and its comorbidities. As part of an
      ongoing initiative to further characterize vervet monkeys originating from St
      Kitts as an animal model of obesity and inflammation, we sequenced and genotyped
      the human ortholog vervet TNF gene and approximately 1 kb of the flanking 3' and
      5' regions from 265 monkeys in a closed, pedigreed colony. This process revealed
      a total of 11 single-nucleotide polymorphisms (SNPs) and a single 4-bp insertion
      deletion, with minor allele frequencies of 0.08 to 0.39. Many of these
      polymorphisms were in strong or complete linkage disequilibrium with each other,
      and all but 1 were contained within a single haplotype block, comprising 5
      haplotypes with frequencies of 0.075 to 0.298. Using sequences from humans,
      chimpanzees, vervets, baboons, and rhesus macaques, phylogenetic shadowing of the
      TNF promoter region revealed that vervet SNPs, like the SNPs in related species,
      were clustered nonrandomly and nonuniformly around conserved transcription factor
      binding sites. These data, combined with previously defined heritable phenotypes,
      permit future association analyses in this nonhuman primate model and have great
      potential to help dissect the genetic and nongenetic contributions to complex
      diseases like obesity. More broadly, the sequence data and comparative analyses
      reported herein facilitates study of the evolution of regulatory sequences of
      inflammatory and immune-related genes.

PMID- 20034436
TI  - Advanced acupuncture system for neurological disorders.

PMID- 20034435
TI  - Epidemiology of invasive Klebsiella pneumoniae with hypermucoviscosity phenotype
      in a research colony of nonhuman primates.
AB  - Invasive Klebsiella pneumoniae with hypermucoviscosity phenotype (HMV K.
      pneumoniae) is an emerging human pathogen that, over the past 20 y, has resulted
      in a distinct clinical syndrome characterized by pyogenic liver abscesses
      sometimes complicated by bacteremia, meningitis, and endophthalmitis. Infections
      occur predominantly in Taiwan and other Asian countries, but HMV K. pneumoniae is
      considered an emerging infectious disease in the United States and other Western
      countries. In 2005, fatal multisystemic disease was attributed to HMV K.
      pneumoniae in African green monkeys (AGM) at our institution. After
      identification of a cluster of subclinically infected macaques in March and April
      2008, screening of all colony nonhuman primates by oropharyngeal and rectal
      culture revealed 19 subclinically infected rhesus and cynomolgus macaques. PCR
      testing for 2 genes associated with HMV K. pneumoniae, rmpA and magA, suggested
      genetic variability in the samples. Random amplified polymorphic DNA analysis on
      a subset of clinical isolates confirmed a high degree of genetic diversity
      between the samples. Environmental testing did not reveal evidence of aerosol or
      droplet transmission of the organism in housing areas. Further research is needed
      to characterize HMV K. pneumoniae, particularly with regard to genetic
      differences among bacterial strains and their relationship to human disease and
      to the apparent susceptibility of AGM to this organism.

PMID- 20034437
TI  - Recent development of acupuncture on Parkinson's disease.
AB  - OBJECTIVES: Parkinson's disease is a complex disease with multiple etiological
      factors involved in disease pathogenesis, and the molecular and cellular pathways
      for neurodegeneration are still elusive. METHODS: We reviewed all the relevant
      laboratory findings regarding acupuncture mechanism on Parkinson's disease.
      RESULTS: Acupuncture treatments in animal experiments have generated valuable
      mechanistic insights of Parkinson's disease and shown that acupuncture therapy is
      in fact a neuroprotective therapy which increases various neuroprotective agents
      such as brain-derived neurotrophic factor, glial cell line-derived neurotrophic
      factor and cyclophilin A. In addition, acupuncture therapy decreases cell death
      processes and attenuates oxidative stress to substantia nigra dopaminergic
      neurons. DISCUSSION: These results suggest that early application of acupuncture
      therapy for Parkinson's disease patients may be helpful for the best efficacy of
      acupuncture treatment.

PMID- 20034438
TI  - Electroacupuncture analgesia in rat ankle sprain pain model: neural mechanisms.
AB  - OBJECTIVES: Acupuncture, an alternative medical therapy with a long history, is
      appealing because it can activate endogenous analgesic mechanisms by minimally
      invasive means. The mechanisms of acupuncture, however, are not well understood
      yet. The following sentence was removed from our original manuscript. One of the
      major problems impeding understanding of the acupuncture mechanism is lack of
      experimental models that mimic various forms of persistent pain that respond to
      acupuncture in humans. METHODS: In this review, we summarize and discuss previous
      and recent findings regarding electroacupuncture-induced analgesia in an ankle
      sprain pain model and the potential underlying mechanisms of acupuncture.
      RESULTS: A novel model of ankle sprain pain is introduced recently and the
      mechanism of electroacupuncture-induced analgesia in this model has been
      explored. The following sentence was removed from our original manuscript. This
      model provides a reproducible and quantifiable index of persistent pain at the
      ankle joint in rats. Acupuncture at a remote site produces long-lasting and
      powerful analgesia. The consistent analgesic effect of acupuncture in this model
      has allowed us to pursue the underlying neural mechanisms. CONCLUSIONS: These
      studies provide insight into the mechanisms of acupuncture analgesia in one
      particular form of persistent pain, and hopefully will allow us to expand our
      knowledge to other painful conditions.

PMID- 20034439
TI  - Acupuncture in accomplishing 'health for all'.
AB  - OBJECTIVE: 'Health for All by the Year of 2000' was a motto of the World Health
      Organization (WHO). The aim of this study was to briefly review recent efforts to
      standardize and improve traditional medicine including acupuncture with a focus
      on the WHO activities for the abovementioned motto, acupuncture and neurological
      conditions. METHODS AND RESULTS: The WHO Western Pacific Regional Office, along
      with the WHO collaborating centers, set standardization with evidence-based
      approaches as a main theme in traditional medicine. WHO International Standard
      Terminologies on Traditional Medicine in the Western Pacific Region was published
      in 2007, listing 3259 items of standard terminology. WHO Standard Acupuncture
      Point Locations in the Western Pacific Region was published in 2008. They will
      improve the reproducibility, validity and accumulation of knowledge in
      acupuncture study and clinical practice, for neurological conditions in
      particular. Other activities in traditional medicine standardization were also
      performed. DISCUSSION: With the help of these standardization processes, 'Health
      for All' may well be established in the future especially for the neurological
      conditions, upon the structure of 'harmony in diversity', a harmony of Western
      conventional medicine and traditional medicine. The collaborative work between
      modern science and the traditional medical treatment, acupuncture, will play an
      important role in establishing this harmony.

PMID- 20034441
TI  - Effect of acupuncture on selective attention for smoking-related visual cues in
      smokers.
AB  - OBJECTIVES: Cue reactivity is a key factor that modulates motivational goal
      directed behavior associated with compulsive drug intake and relapse. We
      investigated the effect of acupuncture on the selective attention to smoking
      related visual cues in smokers, as an index of the severity of drug dependence.
      METHODS: Twenty-nine smokers received real acupuncture (n=15) or sham acupuncture
      (n=14) to the acupuncture point HT7 (Sinmun) for 2 consecutive days after
      quitting smoking. A visual probe task was used to measure the attentional bias
      using neutral or smoking visual cues after the second acupuncture stimulation.
      The cigarette withdrawal scale was also measured on the same day. RESULTS: The
      real acupuncture group showed markedly attenuated attentional bias towards
      smoking cues. The real acupuncture group exhibited significant decrease in
      withdrawal symptoms compared to the sham acupuncture group. The attentional bias
      revealed a significant positive correlation with the smoking withdrawal symptoms
      (r=0.430, p<0.05). DISCUSSION: Acupuncture treatment ameliorated the smoking
      withdrawal symptoms as well as the selective attention to smoking-related visual
      cues in smokers. The selective attention to smoking cues was associated with the
      degree of the cigarette withdrawal symptoms.

PMID- 20034440
TI  - Needle-free acupuncture benefits both patients and clinicians.
AB  - OBJECTIVE: This study examined whether a needle-free acupuncture can be an
      alternative to conventional needle injection acupuncture. METHODS: Patients
      (n=101) suffering myofascial shoulder pain were randomly assigned to either
      needle-free or conventional needle injection acupuncture group. Bee venom was
      administered into GB21 (Gyeonjeong) acupuncture point for both groups. RESULTS:
      Shoulder pain was significantly reduced by the treatment in both groups. Patients
      treated by needle-free acupuncture reported less anxiety, less discomfort and
      fewer adverse events. Clinicians reported that needle-free acupuncture was safe
      but not convenient due to the complexity of the device. DISCUSSION: With
      appropriate adjustments of the current device, needle-free acupuncture can become
      an alternative to the conventional needle injection method.

PMID- 20034442
TI  - Electroencephalogram changes according to the subjective acupuncture sensation.
AB  - OBJECTIVES: The aim of this study was to investigate electroencephalogram
      changes, the electrical activity measured on the scalp, in relation to the items
      of acupuncture sensation questionnaire, based on real-life patients' experiences
      during acupuncture. METHODS: Using a 32 channel digital electroencephalogram
      system, healthy volunteers (n=10) received electroencephalogram examinations over
      four consecutive periods: (1) baseline; (2 and 3) acupuncture needle retention
      only or needle retention plus manipulation in random order; (4) aftermath. Alpha,
      beta and theta band power of electroencephalogram acquired in 30 electrodes were
      analysed in relation to the higher or lower subjective rating of acupuncture
      sensation questionnaire categories: the needle insertion, manipulation and
      retention related items. RESULTS: The group with higher ratings of needle
      retention related questionnaire items showed significant changes in alpha band
      electroencephalogram powers over the periods before, during and after the needle
      retention, while the group with lower ratings did not. When analysed without
      grouping based on higher or lower acupuncture sensation questionnaire ratings,
      electroencephalogram band powers did not show significant difference among four
      periods of acupuncture stimulation except for two electrodes of alpha band and
      two electrodes of theta band. DISCUSSION: These results indicate that acupuncture
      may directly affect electroencephalogram activity and this connection may be
      reflected in the subjective questionnaire items, related to the traditional
      notion of deqi (obtaining qi).

PMID- 20034444
TI  - Susceptibility for ischemic stroke in four constitution medicine is associated
      with polymorphisms of FCGR2A and IL1RN genes.
AB  - OBJECTIVES: To determine the association between Four Constitutional
      classification and Fc fragment of IgG, low affinity of IIa, receptor (FCGR2A) and
      interleukin 1 receptor antagonist (IL1RN) in Korean ischemic stroke patients.
      METHODS: We classified the Four Constitutional types in ischemic stroke patients
      (n=162) and healthy control subjects (n=135), and genotyped FCGR2A and IL1RN
      polymorphisms using direct DNA sequencing and polymerase chain reaction (PCR)
      methods. RESULTS: In the IL1RN polymorphisms, the IL1RN*1/IL1RN*2 genotype
      (OR=5.80, p=0.0142), and in the FCGR2A polymorphisms, the rs7535475 (OR=0.58,
      p=0.0218) and rs7512140 (OR=0.09, p=0.0335), were significantly associated with
      ischemic stroke. The prevalence of IL1RN*1/IL1RN*2 genotype of IL1RN and
      rs7535475 of FCGR2A in greater Yin person ischemic stroke patients were different
      from greater Yin person healthy controls (OR=18.97, p=0.0063; OR=0.38, p=0.0045).
      DISCUSSION: These results suggest that IL1RN*1/IL1RN*2 genotype in greater Yin
      person might be associated with increased risk of ischemic stroke, and rs7535475
      of FCGR2A might be associated with decreased risk of ischemic stroke.
      Furthermore, this relationship could provide the basis for a new approach in
      investigating the etiology of ischemic stroke.

PMID- 20034443
TI  - Short term effects by acupuncture to SP3 on the autonomic blood flow control.
AB  - OBJECTIVES: In this study, we investigated the short term effects of acupuncture
      on autonomic control of blood flow in healthy subjects. We also studied whether
      deqi (obtaining qi) sensations are correlated with these autonomic hemodynamic
      changes. METHODS: The experiment had a randomized, crossover design. Five healthy
      volunteers (age: 18-26 years) participated in this study. Acupuncture (2 Hz
      rotations for 10 seconds to 20 mm deep) was applied either to the acupuncture
      point SP3 or KI2 for 5 minutes. Non-invasively obtained continuous hemodynamic
      measurements of ultrasound Dopplerography were recorded at the radial artery
      before, during and after acupuncture stimulation. Cardiovascular autonomic tone
      was also recorded using power spectral analysis of heart rate variability. After
      acupuncture stimulation, the participants completed the acupuncture perception
      scales to measure the degree of deqi or pain they had experienced. RESULTS:
      Acupuncture stimulation to the acupuncture point SP3, when compared to the
      acupuncture point KI2, decreased the maximum systolic velocity. It also decreased
      low frequency component and increased high frequency component of heart rate
      variability, indicating that the decrease in systolic blood flow velocity was due
      to the increased parasympathetic response. Interestingly, warm, radiating and
      energetic feeling, which are related to deqi, had close correlations with the
      decrease in blood flow velocity. DISCUSSION: Acupuncture stimulation to the
      acupuncture point SP3 modulates the autonomic cardiovascular responses by
      enhancing parasympathetic function, and this may help to understand the
      therapeutic effects of acupuncture.

PMID- 20034445
TI  - Dokhwaljihwang-tang inhibits LPS-induced inflammatory cytokine production in
      peripheral blood mononuclear cells.
AB  - OBJECTIVES: Dokhwaljihwang-tang, one of the prescriptions in Four Constitution
      medicine, has been used to treat neurological disorders. This work was aimed to
      examine the effect of Dokhwaljihwang-tang on lipopolysaccharide-induced
      inflammatory cytokine production in peripheral blood mononuclear cells from the
      lesser yang subjects. METHODS: The inflammatory cytokines, interleukin 1 beta,
      interleukin 4 and tumor necrosis factor were measured using the ELISA. The
      interleukin 1 beta mRNA expression was evaluated with reverse transcriptase
      polymerase chain reaction. The expression level of nuclear factor kappa B was
      examined by western blotting. RESULTS: Dokhwaljihwang-tang significantly
      inhibited interleukin 1 beta and interleukin 4 production (p<0.05). When
      Dokhwaljihwang-tang was pre-treated at the dose of 1 mg/ml, it not only decreased
      the interleukin 1 beta mRNA expression, but also inhibited the activation of
      nuclear factor kappa B. DISCUSSION: These results suggest the potential of
      Dokhwaljihwang-tang as a source of pharmaceutical acupuncture for neuronal
      inflammatory diseases.

PMID- 20034446
TI  - Inhibitory effect of Agrimoniae Herba on lipopolysaccharide-induced nitric oxide
      and proinflammatory cytokine production in BV2 microglial cells.
AB  - OBJECTIVES: Agrimoniae Herba has been used as an anti-inflammatory agent in
      traditional medicine. Nitric oxide and proinflammatory cytokines produced by
      activated microglia may be a possible etiological factor of neurodegenerative
      disorders. We evaluated whether Agrimoniae Herba could have an anti-inflammatory
      effect on lipopolysaccharide-induced BV2 microglial cells. METHODS: The effects
      of Agrimoniae Herba on lipopolysaccharide-induced nitric oxide and
      proinflammatory cytokine production in BV2 microglial cells were evaluated by
      nitric oxide assay, enzyme-linked immunosorbent assay and western blotting.
      RESULTS: Agrimoniae Herba had no cytotoxicity and suppressed lipopolysaccharide
      induced nitric oxide production in BV2 microglial cells. Agrimoniae Herba also
      suppressed lipopolysaccharide-induced production of proinflammatory cytokines
      such as tumor necrosis factor, interleukin 1 beta and interleukin 6 in a dose
      dependent manner. Agrimoniae Herba inhibited the expression of inducible nitric
      oxide synthase. DISCUSSION: Taken together, these findings indicate that
      Agrimoniae Herba may be used as a form of pharmaceutical acupuncture therapy in
      the treatment of brain inflammation.

PMID- 20034447
TI  - Inhibitory effect of Angelicae Tenuissimae Radix on expressions of cyclooxygenase
      2 and inducible nitric oxide synthase in mouse BV2 microglial cells.
AB  - OBJECTIVES: Angelicae Tenuissimae Radix has traditionally been used for treating
      headache, flu-like symptoms, limb-ache and disability, and even for treating
      toothache. We investigated the anti-inflammatory and analgesic effect of
      Angelicae Tenuissimae Radix on lipopolysaccharide-induced inflammation. METHODS:
      For this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay, reverse transcription-polymerase chain reaction, prostaglandin E(2)
      immunoassay and nitric oxide detection in mouse BV2 microglial cells were
      performed. RESULTS: Angelicae Tenuissimae Radix suppressed prostaglandin E(2)
      synthesis and nitric oxide production by inhibiting the lipopolysaccharide
      induced expressions of cyclooxygenase-2 and inducible nitric oxide synthase
      messenger RNA in mouse BV2 microglial cells. DISCUSSION: The present study
      indicates that Angelicae Tenuissimae Radix can be applied as a valuable treatment
      for brain inflammation and headache.

PMID- 20034448
TI  - Spatiotemporal patterns of neural activity in response to electroacupuncture
      stimulation in the rodent primary somatosensory cortex.
AB  - OBJECTIVES: Optical imaging technique enables the recording of cortical
      activities in multiple sites of the primary somatosensory cortex in real time.
      The present study was aimed to visualize neural activity in response to the
      acupuncture stimulation in the rodent primary somatosensory cortex by a high
      resolution optical imaging system using voltage-sensitive dyes. METHODS: Optical
      imaging was exploited to examine the temporal-spatial characteristic of rat
      primary somatosensory cortex during electroacupuncture stimulation (6 mA
      intensity and 2 ms duration) at two pairs of acupuncture points (ST36-SP6 or GB34
      BL57). RESULTS: In terms of magnitude and duration of the optical response, there
      was no difference between ST36-SP6 and GB34-BL57 stimulations. Maximally
      activated sites by electroacupuncture stimulation to the different acupuncture
      points were spatially differentiated in rat primary somatosensory cortex.
      DISCUSSION: The results indicate that neuronal responses to electroacupuncture
      stimulation can be visualized in rat primary somatosensory cortex using an
      optical imaging system. The topographical mapping of acupuncture points in
      primary somatosensory cortex will make a significant contribution to the
      understanding of neural mechanisms of the acupuncture treatment and Meridian
      phenomena.

PMID- 20034449
TI  - Effect by acupuncture on hypothalamic expression of maternally separated rats:
      proteomic approach.
AB  - OBJECTIVES: Early stressors can influence the development of biological and
      neurological systems. Maternal separation (social isolation) in early life may
      increase vulnerability to neurodegenerative diseases and neuropsychiatric
      disorders over the lifespan. To identify new proteins on acupuncture effects in
      maternally separated rats, an animal model for study of early environmental
      insults, proteomic approach on the expression of the hypothalamic proteins was
      performed. METHODS: On post-natal day 14, rat pups were randomly divided into
      four groups: pups kept with their mothers for 7 days; pups kept with their
      mothers with acupuncture daily to HT8 (Sobu); maternally separated pups;
      maternally separated pups with acupuncture. The hypothalamic proteins were
      analysed by two-dimensional electrophoresis coupled with matrix assisted laser
      desorption/ionization time-of-flight mass spectrometer. RESULTS: The results
      showed that 27 spots were differentially and commonly expressed. Of 27 spots, 21
      spots were identified while six spots were not, and 15 proteins were known
      proteins. In maternally separated group, the expressions of 14 proteins were down
      regulated, compared to control group. In group of maternally separation with
      acupuncture, five proteins were down-regulated and nine were up-regulated,
      compared to the maternally separated group. Among nine proteins up-regulated by
      acupuncture treatment, we found four proteins (dihydropyrimidinase-like 2,
      dystrophin-related protein 2, tubulin, alpha 1a and syntaxin 1b) related to
      neurodevelopment. DISCUSSION: The result suggests that acupuncture to HT8 may
      affect neurodevelopment, and acupuncture may be a possible therapy for
      neurodevelopmental disorders.

PMID- 20034450
TI  - Gene expression profile of acupuncture treatment in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced Parkinson's disease model.
AB  - OBJECTIVES: To find new biomarkers by stimulating acupuncture point GB34
      (Yangneungcheon) which has neuroprotective effect on the mouse model of
      Parkinson's disease, analysis of cDNA microarray on mRNAs of the substantia nigra
      was performed. METHODS: Male C57BL/6 mice were divided into two groups: 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine-treated mice (MPTP group, n=3); 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine and acupuncture (GB34)-treated mice (MPTP + ACU
      group, n=3). The mice received an intraperitoneal injection of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (30 mg/kg) once daily for 3 consecutive days. Manual
      acupuncture was performed 2 hours after every injection of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine. The total RNA in the substantia nigra of each mouse
      was isolated on 3 days after the last 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine injection. Agilent mouse whole genome 44K chip was used for
      microarray analysis and the hybridization image was analysed by GenePix Pro 6.0.
      Data normalization and analysis were performed using GeneSpring GX 7.3.1 program.
      RESULTS: The acupuncture stimulation revealed 799 genes (424 up- and 375 down
      regulated) of which expression levels were changed more than two-folds in the
      MPTP + ACU group, compared to the MPTP group. The genes selected were classified
      into several categories based on their functions using DAVID Bioinformatics
      Resources 2008 (http://david.abcc.ncifcrf.gov/) and KEGG PATHWAY Database
      (http://www.genome.jp/kegg/pathway.html). DISCUSSION: Biomarkers in response to
      acupuncture stimulation to GB34 were identified in a mouse model for Parkinson's
      disease. These biomarkers might provide a promising clue for understanding the
      neuroprotective effect of acupuncture in Parkinson's disease.

PMID- 20034451
TI  - Acupuncture attenuates extracellular glutamate level in global ischemia model of
      rat.
AB  - OBJECTIVES: Acupuncture has been known to be effective in ischemia, and glutamate
      excitotoxicity is an important factor for the neuronal cell death. We examined
      the effect of acupuncture on glutamate level in the ischemic stroke model.
      METHODS: A global ischemia was induced using the method of 11-vessel occlusion in
      rat. Rats were randomly divided into two groups: the control group (n=5, with 11
      vessel occlusion) and the acupuncture group (n=5, with 11-vessel occlusion +
      acupuncture). The extracellular glutamate level was assessed using an
      intracerebral biosensor system measuring 256 samples per second. Simultaneously,
      the cerebral blood flow was measured and the electroencephalogram data were
      recorded. The time schedule of the experiment was as follows: 10 minutes of
      baseline measurement, 10 minutes of occlusion and 30 minutes of follow-up
      monitoring. Acupuncture stimulation was applied to the acupuncture points GB34
      (Yangneungcheon) and GB39 (Hyeonjong) during the occlusion period. RESULTS: In
      the control group, the extracellular glutamate level was changed as 135.19 +/-
      23.76 microM (mean +/- standard deviation) from the baseline level. However, this
      increase was suppressed in the acupuncture group (72.20 +/- 27.15 microM, p<0.01
      versus the control group). The changes of cerebral blood flow and
      electroencephalogram were not significantly different between the groups.
      DISCUSSION: This result suggests that the effect of acupuncture might be closely
      associated with modulation of the brain glutamate release in the ischemic
      condition.

PMID- 20034452
TI  - Acupuncture attenuates neuronal cell death in middle cerebral artery occlusion
      model of focal ischemia.
AB  - OBJECTIVES: This study was designed to investigate the neuroprotective effect of
      acupuncture in the middle cerebral artery occlusion-induced ischemia model.
      METHODS: Sprague-Dawley rats were randomly divided into two experimental groups:
      middle cerebral artery occlusion group (MCAO, n=8), and middle cerebral artery
      occlusion plus acupuncture group (MCAO + Acu, n=8). Acupuncture stimulation was
      given immediately after reperfusion. The effect of its stimulation to both GB34
      and GB39 on the size of the brain infarct and the functional status of the brain
      cells after middle cerebral artery occlusion was examined by nissl staining and
      neuron-specific nuclear protein immunohistochemistry. RESULTS: The infarction
      volume was significantly decreased in the MCAO + Acu group (16.4 +/- 4.8%),
      compared with the MCAO group (39.9 +/- 10.2%). The number of neuron-specific
      nuclear protein-positive cells in the MCAO group was significantly decreased by
      42.3 +/- 12.6% in the striatum and by 45.8 +/- 5.8% in the motor cortex, but the
      neuron-specific nuclear protein-positive cells in the MCAO + Acu group were
      rescued by 67.0 +/- 3.8% in the striatum and by 68.1 +/- 4.5% in the motor
      cortex, compared with the contralateral side (100%). DISCUSSION: This study
      showed that acupuncture had neuroprotective effects against focal ischemia in the
      middle cerebral artery occlusion model.

PMID- 20034453
TI  - Neuroprotective effects of bee venom pharmaceutical acupuncture in acute 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease.
AB  - OBJECTIVES: We explored the neuroprotective effects of bee venom acupuncture in
      acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of
      Parkinson's disease. METHODS: Male C57BL/6 mice were divided into three groups:
      saline-injected control group, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      injected group and bee venom acupuncture-pretreated plus 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine-injected group. Mice were injected with 0.02 ml bee
      venom (1 : 2000 w/v) to GB34 (Yangneungcheon) bilaterally once every 3 days for 2
      weeks. After 2 weeks' pre-treatment, the mice were injected with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (20 mg/kg, i.p.) four times in 2 hour
      intervals. Tyrosine hydroxylase and phospho-Jun immunoreactivities in the
      substantia nigra and striatum were observed 3 days after 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine injection. RESULTS: Bee venom acupuncture prevented
      the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced loss of tyrosine
      hydroxylase immunoreactivity in the substantia nigra and striatum. Moreover, bee
      venom acupuncture attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
      phospho-Jun immunoreactivity in the substantia nigra. DISCUSSION: We found that
      bee venom acupuncture effectively protected dopaminergic neurons against 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine toxicity, possibly through inhibition of Jun
      activation. Our results suggest that bee venom acupuncture could be a potential
      preventive agent for Parkinson's disease.

PMID- 20034454
TI  - Acupuncture manipulation enhances anti-nociceptive effect on formalin-induced
      pain in rats.
AB  - OBJECTIVES: In order to apply appropriate acupuncture stimulation, different
      needle manipulation techniques are required. These manipulations are performed in
      many ways such as twirling the needle, varying the insertion angle, etc. The
      present study was designed to evaluate the antinociceptive effect of these
      manipulations to the acupuncture point ST36 on formalin-induced pain in rats.
      METHODS: Animals were divided into four groups: non-treated control (CON),
      acupuncture without manipulation (AT), acupuncture with twirling manipulation
      (TM) and acupuncture with lifting-thrusting manipulation (LM) group. Level of
      pain was measured in formalin-injected rats in the early (0-10 minutes) and the
      late (10-60 minutes) phase. Several pain-related gene expressions were
      investigated in the spinal cord using reverse transcriptase-polymerase chain
      reaction analysis. RESULTS: Formalin-induced pain was significantly reduced in
      the TM and the LM groups, compared with the CON and the AT groups. TM was more
      effective than LM in both phases. Needle manipulation was also effective in
      suppressing the mRNA expression of pain-related genes such as Fos, opioid
      receptor-like 1, tachykinin 1, tachykinin receptor 1, mu-opioid receptor and 5
      hydroxytryptamine receptor 2A in the spinal cord. DISCUSSION: The TM and the LM
      groups showed enhanced analgesia, compared with the AT group. This effect might
      be related to the suppression of the transcription of pain-related genes.

PMID- 20034455
TI  - Acute electroacupuncture inhibits nitric oxide synthase expression in the spinal
      cord of neuropathic rats.
AB  - OBJECTIVES: To examine the effects of electroacupuncture stimulation on
      behavioral changes and neuronal nitric oxide synthase expression in the rat
      spinal cord after nerve injury. METHODS: Under pentobarbital anesthesia, male
      Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and
      cutting the left tibial and sural nerves. Behavioral responses to mechanical
      stimulation were tested for 2 weeks post-operatively. At the end of behavioral
      testing, electroacupuncture stimulation was applied to ST36 (Choksamni) and SP9
      (Eumleungcheon) acupoints. Immunocytochemical staining was performed to
      investigate changes in the expression of neuronal nitric oxide synthase
      immunoreactive neurons in the L4-5 spinal cord. RESULTS: Mechanical allodynia was
      observed by nerve injury. The mechanical allodynia was decreased after
      electroacupuncture stimulation. Neuronal nitric oxide synthase expression was
      also decreased in L4-5 spinal cord by electroacupuncture treatment. DISCUSSION:
      These results suggest that electroacupuncture relieves mechanical allodynia in
      the neuropathic rats possibly by the inhibition of neuronal nitric oxide synthase
      expression in the spinal cord.

PMID- 20034456
TI  - Bee venom suppresses methamphetamine-induced conditioned place preference in
      mice.
AB  - OBJECTIVES: Although acupuncture is most commonly used for its analgesic effect,
      it has also been used to treat various drug addictions including cocaine and
      morphine in humans. This study was designed to investigate the effect of bee
      venom injection on methamphetamine-induced addictive behaviors including
      conditioned place preference and hyperlocomotion in mice. METHODS:
      Methamphetamine (1 mg/kg) was subcutaneously treated on days 1, 3 and 5 and the
      acquisition of addictive behaviors was assessed on day 7. After confirming
      extinction of addictive behaviors on day 17, addictive behaviors reinstated by
      priming dose of methamphetamine (0.1 mg/kg) was evaluated on day 18. Bee venom
      (20 microl of 1 mg/ml in saline) was injected to the acupuncture point ST36 on
      days 1, 3 and 5. RESULTS: Repeated bee venom injections completely blocked
      development of methamphetamine-induced acquisition and subsequent reinstatement.
      Single bee venom acupuncture 30 minutes before acquisition and reinstatement test
      completely inhibited methamphetamine-induced acquisition and reinstatement.
      Repeated bee venom acupunctures from day 8 to day 12 after methamphetamine
      induced acquisition partially but significantly suppressed reinstatement.
      DISCUSSION: These findings suggest that bee venom acupuncture has a preventive
      and therapeutic effect on methamphetamine-induced addiction.

PMID- 20034457
TI  - Morphine-induced locomotor response and Fos expression in rats are inhibited by
      acupuncture.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of acupuncture to
      the acupuncture point HT7 (Sinmun) on morphine-induced behavioral sensitization
      and the neuronal changes in nucleus accumbens and striatum in rats. METHODS: Male
      Sprague-Dawley rats were given repeated injections of morphine hydrochloride for
      5 days followed by 3 day withdrawal and one challenge injection. The acupuncture
      treatment was performed for 1 minute once a day for 3 days of withdrawal period
      and its effect on morphine-induced changes of locomotor activity and Fos
      expression was examined. RESULTS: The acupuncture stimulation to HT7
      significantly suppressed the morphine-induced increases in the locomotor activity
      and Fos expression in the nucleus accumbens and striatum, as compared to the
      controls of non-acupoint or the acupoint on other meridian. DISCUSSION: These
      results demonstrated that the inhibitory effect of the acupuncture stimulation to
      HT7 on morphine-induced behavioral sensitization was closely associated with the
      suppression of dopamine biosynthesis and its activity in the post-synaptic
      neurons in nucleus accumbens and striatum. It means that the behavioral effect of
      the acupuncture can originate from the modulation of the same neuronal mechanism
      in the central dopaminergic system as in the morphine-induced behavioral
      sensitization. This modulation was also strictly confined to the stimulation of
      the specific acupoint, because the stimulation to other acupoint (TE5) on another
      meridian did not show the modulating effect despite being relatively close to
      each other. It can be therefore suggested that the acupuncture stimulation has an
      acupoint-specific property, and might be a useful therapeutic alternative with
      few side effects for treating morphine addiction.

PMID- 20034458
TI  - Electroacupuncture to ST36 ameliorates behavioral and biochemical responses to
      restraint stress in rats.
AB  - OBJECTIVES: Acupuncture has been used for the treatment and prevention of stress
      related disorders. In the present study, the effect of electroacupuncture on the
      behavioral and biochemical responses to restraint stress was evaluated in rats.
      METHODS: Sprague-Dawley male rats underwent immobilization stress for 21 days (6
      hours/day). Electroacupuncture (2 Hz, 2 mA and 10 minutes) was applied either to
      the acupuncture point ST36 (Joksamni) or the non-acupuncture point in the tail
      for the last 7 days. Rats were randomly divided into four groups: the normal
      group (n=10, without the restraint stress), the stress group (n=10, with
      restraint stress), the ST36 group (n=10, with restraint stress and
      electroacupuncture to ST36) and the non-acupuncture group (n=10, with restraint
      stress and electroacupuncture to the non-acupuncture point). The anxiety-related
      behavior was tested using the elevated plus maze and the Vogel test on day 22.
      The serum concentration of corticosterone was determined using an enzyme-linked
      immunosorbent assay kit. The expression of tyrosine hydroxylase in the locus
      coeruleus was measured by immunohistochemistry. RESULTS: Restraint stress
      increased the response of the anxiety-related behavior. The serum level of
      corticosterone and the number of tyrosine hydroxylase-immunoreactive cells were
      also increased. The ST36 group showed a significant decrease of anxiety-related
      behavioral response, compared with the stress group. The serum corticosterone
      level and tyrosine hydroxylase-immunoreactive expression were also decreased in
      the ST36 group. DISCUSSION: These findings suggest that electroacupuncture to
      ST36 might play a role in reducing the stress-related responses, which may be
      helpful for the treatment of stress-related disorders.

PMID- 20034459
TI  - Electroacupuncture induces Fos expression in the nucleus tractus solitarius via
      cholecystokinin A receptor signaling in rats.
AB  - OBJECTIVES: Cholecystokinin, a satiety hormone, acts on cholecystokinin A
      receptor on vagal afferent neurons that project to the nucleus tractus
      solitarius, resulting in inhibition of feeding. Cholecystokinin is known to be
      released by electroacupuncture stimulation at certain body sites which elicits
      profound psychophysiological responses. Our previous study has revealed the
      involvement of cholecystokinin and cholecystokinin A receptor in the
      electroacupuncture stimulation-induced modulation of feeding. The aim of the
      present study was to examine whether electroacupuncture stimulation at the
      acupuncture point ST36 (Joksamni) activates the nucleus tractus solitarius
      neurons and whether such effect is mediated by cholecystokinin A receptor.
      METHODS: Using an immunofluorescent analysis of Fos, a neuronal activation
      marker, we compared the Fos immunoreactivity of the nucleus tractus solitarius
      among three groups of Sprague-Dawley rats: (1) control (48 hour fasting + saline
      pre-treatment + no electroacupuncture stimulation); (2) SalEA (48 hour fasting +
      saline pre-treatment + ST36 electroacupuncture stimulation); (3) LorEA (48 hour
      fasting + pre-treatment of cholecystokinin A receptor antagonist, lorglumide +
      ST36 electroacupuncture stimulation). RESULTS: ST36 electroacupuncture
      stimulation significantly reduced 30 minute food intake (p<0.05, SalEA versus
      control) and increased Fos expression in the nucleus tractus solitarius (p<0.01,
      SalEA versus control). The effects of electroacupuncture on food intake and Fos
      were blocked by a lorglumide pre-treatment (p>0.05, LorEA versus control).
      DISCUSSION: Our finding suggests that ST36 electroacupuncture stimulation
      activates the nucleus tractus solitarius neurons via cholecystokinin A receptor
      signaling pathway, which may be the underlying central mechanism of
      electroacupuncture-induced satiety effect.

PMID- 20034460
TI  - Biochemical analysis of a recombinant glutathione transferase from the cestode
      Echinococcus granulosus.
AB  - Glutathione transferases (GSTs) are believed to be a major detoxification system
      in helminths. We describe the expression and functional analysis of EgGST, a
      cytosolic GST from Echinococcus granulosus, related to the Mu-class of mammalian
      enzymes. EgGST was produced as an enzymatically active dimeric protein (rEgGST),
      with highest specific activity towards the standard substrate 1-chloro-2,4
      dinitrobenzene (CDNB; 2.5 micromol min(-1)mg(-1)), followed by ethacrynic acid.
      Interestingly, rEgGST displayed glutathione peroxidase activity (towards cumene
      hydroperoxide), and conjugated reactive carbonyls (trans-2-nonenal and
      trans,trans-2,4-decadienal), indicating that it may intercept damaging products
      of lipid peroxidation. In addition, classical GST inhibitors (cybacron blue,
      triphenylthin chloride and ellagic acid) and a number of anthelmintic drugs
      (mainly, hexachlorophene and rafoxanide) were found to interfere with glutathione
      conjugation to CDNB; suggesting that they may bind to EgGST. Considered globally,
      the functional properties of rEgGST are similar to those of putative orthologs
      from Echinococcus multilcularis and Taenia solium, the other medically important
      cestodes. Interestingly, our results also indicate that differences exist between
      these closely related cestode GSTs, which probably reflect specific biological
      functions of the molecules in each parasitic organism.

PMID- 20034461
TI  - Proteasomal activity in skeletal muscle: a matter of assay design, muscle type,
      and age.
AB  - The ubiquitin-proteasome system (UPS) is a major degradation system for
      regulatory and misfolded proteins. UPS function has been implicated to exert a
      central role in the pathogenesis of various human diseases. Because biochemical
      analyses are often hampered by the amount of available diseased tissue, we report
      on the establishment and validation of a luminescence-based proteasomal activity
      assay applicable to 5-mg quantities of skeletal muscle. We demonstrate that the
      specific proteasomal activity differs in individual muscle groups and decreases
      with aging. These findings warrant the use of appropriate controls and a careful
      interpretation of results in mammalian skeletal muscle pathologies.

PMID- 20034462
TI  - Farnesyltransferase inhibitor improved survival following endotoxin challenge in
      mice.
AB  - Endotoxemia plays an important role in the pathogenesis of sepsis and is
      accompanied by dysregulated apoptosis of immune and non-immune cells. Treatment
      with statins reduces mortality in rodent models of sepsis and endotoxemia.
      Inhibition of protein isoprenylation, including farnesylation, has been proposed
      as a mechanism to mediate the lipid-lowering-independent effects of statins.
      Nonetheless, the effects of the inhibition of isoprenylation have not yet been
      studied. To investigate the role of farnesylation, we evaluated the effects of
      farnesyltransferase inhibitor and statin on survival following lipopolysaccharide
      (LPS) challenge in mice. Both simvastatin (2mg/kg BW) and FTI-277 (20mg/kg BW)
      treatment improved survival by twofold after LPS injection, as compared with
      vehicle alone (p<0.01). LPS-induced cleavage (activation) of caspase-3, an
      indicator of apoptotic change, and increased protein expression of proapoptotic
      molecules, Bax and Bim, and activation of c-Jun NH(2)-terminal kinase (JNK/SAPK)
      in the liver and spleen were attenuated by both simvastatin and FTI-277. These
      results demonstrate that farnesyltransferase inhibitor as well as statin
      significantly reduced LPS-induced mortality in mice. Our findings also suggest
      that inhibition of protein farnesylation may contribute to the lipid-lowering
      independent protective effects of statins in endotoxemia, and that protein
      farnesylation may play a role in LPS-induced stress response, including JNK/SAPK
      activation, and apoptotic change. Our data argue that farnesyltransferase may be
      a potential molecular target for treating patients with endotoxemia.

PMID- 20034463
TI  - Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast
      adenocarcinoma cells to radiation-induced apoptosis.
AB  - Chemoresistant tumors often fail to respond to other cytotoxic treatments such as
      radiation therapy. The mechanisms of chemo- and radiotherapy cross resistance are
      not fully understood and are believed to be epigenetic in nature. We hypothesize
      that MCF-7 cells and their doxorubicin-resistant variant MCF-7/DOX cells may
      exhibit different responses to ionizing radiation due to their dissimilar
      epigenetic status. Similar to previous studies, we found that MCF-7/DOX cells
      harbor much lower levels of global DNA methylation than MCF-7 cells. Furthermore,
      we found that MCF-7/DOX cells had lower background apoptosis levels and were less
      responsive to radiation than MCF-7 cells. Decreased radiation responsiveness
      correlated to significant global DNA hypomethylation in MCF-7/DOX cells. Here,
      for the first time, we show that the radiation resistance of MCF-7/DOX cells can
      be reversed by an epigenetic treatment--the application of methyl-donor SAM. SAM
      mediated reversal of DNA methylation led to elevated radiation sensitivity in MCF
      7/DOX cells. Contrarily, application of SAM on the radiation sensitive and higher
      methylated MCF-7 cells resulted in a decrease in their radiation responsiveness.
      This data suggests that a fine balance of DNA methylation is needed to insure
      proper radiation and drug responsiveness.

PMID- 20034464
TI  - Enhanced RIG-I expression is mediated by interferon regulatory factor-2 in
      peripheral blood B cells from hepatitis C virus-infected patients.
AB  - Chronic hepatitis C patients carry the risk of developing into B-cell non
      Hodgkin's lymphoma (B-NHL). To clarify the mechanisms underlying this
      association, we first investigated the molecular markers of B cells from
      hepatitis C virus (HCV)-infected patients. CD19-positive cells were isolated as B
      cells from the peripheral blood mononuclear cells of patients infected with the
      hepatitis C virus and IFN-related gene expression was analyzed. We found that RIG
      I and IRF-2 expression were up-regulated in CD19-positive cells from the infected
      patients. In vitro luciferase reporter analysis using human cell lines indicated
      that IRF-2 activates the human RIG-I promoter. IRF-2 expression levels were
      enhanced by HCV cDNA transfection in Huh7 cells. In addition, we observed much
      less induction in the interferon stimulated gene 15 (ISG15) after Sendai virus
      (SenV) stimulation of CD19-positive cells from infected patients versus healthy
      controls, thereby suggesting an impairment of RIG-I downstream signaling in HCV
      infected patients. Hence, we found that the failure of the anti-viral response
      with enhanced IRF-2 oncogenic protein expression in blood B cells from HCV
      infected patients. Our results provide important information to better understand
      the role of IRFs in the cause of HCV chronic infection.

PMID- 20034465
TI  - Triazole-containing BODIPY dyes as novel fluorescent probes for soluble oligomers
      of amyloid Abeta1-42 peptide.
AB  - A straightforward functionalization of BODIPY dyes via incorporation of a
      triazole moiety produced fluorescent dyes that were capable of distinguishing
      between secondary structure conformations of soluble oligomeric species of Abeta1
      42 peptide. Small concentrations of the dyes, relative to Abeta1-42, provided up
      to an 8-fold and 35-fold fluorescence increase in the presence of the unordered
      and ordered, beta-sheet-rich conformations of soluble Abeta1-42 oligomers,
      respectively. These triazole-containing dyes could prove to be useful probes for
      monitoring amyloid conformational transitions in vitro.

PMID- 20034466
TI  - Similar effects of resistin and high glucose on P-selectin and fractalkine
      expression and monocyte adhesion in human endothelial cells.
AB  - Resistin and high glucose (HG) are concomitantly present at elevated
      concentration in diabetic's plasma; both are pro-inflammatory agents acting on
      vascular cells by mechanisms that are not fully understood. We questioned whether
      resistin and HG affect the expression of major adhesion molecules, P-selectin and
      fractalkine in human endothelial cells (HEC). The results showed that in HEC (i)
      resistin increased P-selectin expression; (ii) HG up-regulated Fk expression;
      (iii) P-selectin and fractalkine were functional increasing monocyte adhesion to
      activated cells. Co-stimulation with resistin and HG increased P-selectin and
      fractalkine mRNA and protein and induced monocyte adhesion, generated an increase
      in NADPH oxidase activity and of the intracellular reactive oxygen species and
      activated the NF-kB and AP-1 transcription factors at similar values as those of
      each activator. In conclusion in HEC, resistin and HG induce the up-regulation of
      P-selectin and fractalkine and the ensuing increased monocyte adhesion by a
      mechanism involving oxidative stress and NF-kB and AP-1 activation.

PMID- 20034467
TI  - An efficient and rapid method for gene cloning from eukaryotic genomic DNA using
      overlap-PCR: With an example of cattle Ghrelin gene.
AB  - In this study, overlap-PCR, an efficient and rapid method, was used to clone
      cattle Ghrelin gene CDS (coding sequence) from genomic DNA. The procedure
      included seven primers and three-step PCRs. Cattle Ghrelin gene consists of four
      exons and the CDS contains 351 bps. In the first step three PCRs were performed
      to generate extended exon1, exon2, and exon3 that contained overlapped
      nucleotides and were used as the templates for second ligation PCR. Secondly,
      exon1 and exon2 were spliced together. And it was same with exon3 and exon4.
      Lastly, the four exons were linked together with outermost primers and the
      templates from the second step. Comparison analysis on the obtained CDS of
      Ghrelin gene and cDNA by RT-PCR showed that the two sequences were same. As an
      efficient and rapid method, overlap-PCR is feasible and acceptable for gene
      cloning from genomic DNA.

PMID- 20034468
TI  - Mesenchymal stem cells cultured under hypoxia escape from senescence via down
      regulation of p16 and extracellular signal regulated kinase.
AB  - Hypoxia has been considered to affect the properties of tissue stem cells
      including mesenchymal stem cells (MSCs). Effects of long periods of exposure to
      hypoxia on human MSCs, however, have not been clearly demonstrated. MSCs cultured
      under normoxic conditions (20% pO(2)) ceased to proliferate after 15-25
      population doublings, while MSCs cultured under hypoxic conditions (1% pO(2))
      retained the ability to proliferate with an additional 8-20 population doublings.
      Most of the MSCs cultured under normoxic conditions were in a senescent state
      after 100days, while few senescent cells were found in the hypoxic culture, which
      was associated with a down-regulation of p16 gene expression. MSCs cultured for
      100days under hypoxic conditions were superior to those cultured under normoxic
      conditions in the ability to differentiate into the chondro- and adipogenic, but
      not osteogenic, lineage. Among the molecules related to mitogen-activated protein
      kinase (MAPK) signaling pathways, extracellular signal regulated kinase (ERK) was
      significantly down-regulated by hypoxia, which helped to inhibit the up
      regulation of p16 gene expression. Therefore, the hypoxic culture retained MSCs
      in an undifferentiated and senescence-free state through the down-regulation of
      p16 and ERK.

PMID- 20034469
TI  - Differential binding of ICln in platelets to integrin-derived activating and
      inhibitory peptides.
AB  - The capacity of platelets to form a thrombus is mediated by integrin
      alpha(IIb)beta(3). The cytoplasmic tail of alpha(IIb) contains a highly conserved
      motif, (989)KVGFFKR(995), which plays a critical role in regulating integrin
      activation and acts as a recognition site for various intracellular proteins,
      e.g. CIB1, PP1, ICln and RN181. Previously, we demonstrated that a cell-permeable
      integrin-derived activating (IDA) peptide, KVGFFKR, induces platelet activation,
      whereas an integrin-derived inhibitory (IDI) peptide, KVGAAKR, is antithrombotic.
      To elucidate the molecular mechanism underlying these opposite effects we
      investigate the affinity of known integrin alpha(IIb) binding proteins for the
      two immobilized peptides in dependence on the activation state of platelets by
      means of peptide-affinity chromatography, blotting techniques and protein:peptide
      docking studies. Our results provide a model for the inhibition of ICln
      interaction with the integrin in activated platelets by the IDI-peptide. Thus,
      ICln:IDI-peptide interaction profiles can have a pivotal purpose in the search
      for consensus pharmacophores specifically inhibiting ICln function in platelets
      potentially leading to the development of integrin-derived antithrombotic drugs.

PMID- 20034470
TI  - Mutant proinsulin proteins associated with neonatal diabetes are retained in the
      endoplasmic reticulum and not efficiently secreted.
AB  - Mutations in the preproinsulin protein that affect processing of preproinsulin to
      proinsulin or lead to misfolding of proinsulin are associated with diabetes. We
      examined the subcellular localization and secretion of 13 neonatal diabetes
      associated human proinsulin proteins (A24D, G32R, G32S, L35P, C43G, G47V, F48C,
      G84R, R89C, G90C, C96Y, S101C and Y108C) in rat INS-1 insulinoma cells. These
      mutant proinsulin proteins accumulate in the endoplasmic reticulum (ER) and are
      poorly secreted except for G84R and in contrast to wild-type and
      hyperproinsulinemia-associated mutant proteins (H34D and R89H) which were sorted
      to secretory granules and efficiently secreted. We also examined the effect of
      C96Y mutant proinsulin on the synthesis and secretion of wild-type insulin and
      observed a dominant-negative effect of the mutant proinsulin on the synthesis and
      secretion of wild-type insulin due to induction of the unfolded protein response
      and resulting attenuation of overall translation.

PMID- 20034471
TI  - Jab1 regulates levels of endothelin type A and B receptors by promoting
      ubiquitination and degradation.
AB  - Endothelin type A receptor (ET(A)R) plays an important role in some
      cardiovascular disorders where ET(A)R levels are increased. However, regulatory
      mechanisms for ET(A)R levels are unknown. Here, we identified Jun activation
      domain-binding protein 1 (Jab1) as an ET(A)R-interacting protein by yeast two
      hybrid screening of human heart cDNA library using carboxyl terminal tail (C
      tail) of ET(A)R as a bait. The interaction was confirmed by glutathione S
      transferase pull-down assay, co-immunoprecipitation in HEK293T cells expressing
      ET(A)R-myc and FLAG-Jab1, and confocal microscopy. Jab1 knockdown increased whole
      cell and cell surface levels of ET(A)R and ET-1-induced ERK1/2 phosphorylation in
      HEK293T cells expressing ET(A)R, whereas Jab1 overexpression decreased them. Jab1
      overexpression accelerated disappearance rate of ET(A)R after protein synthesis
      inhibition as an index of a degradation rate. ET(A)R was constitutively
      ubiquitinated, and the level of ubiquitination was enhanced by Jab1
      overexpression. Long-term ET-1 stimulation markedly accelerated the rate of
      ET(A)R degradation and increased the amount of Jab1 bound to ET(A)R with a
      maximal level of 500% at 3h. In the absence of ET-1 stimulation, the level of
      ET(B)R was lower than that of ET(A)R and the degradation rate of ET(B)R was
      markedly faster than that of ET(A)R. Notably, the amount of Jab1 bound to ET(B)R
      and ubiquitination level of ET(B)R were markedly higher than those for ET(A)R.
      Taken together, these results suggest that the amount of Jab1 bound to ETR
      regulates the degradation rate of ET(A)R and ET(B)R by modulating ubiquitination
      of these receptors, leading to changes in ET(A)R and ET(B)R levels.

PMID- 20034472
TI  - miR-126 inhibits non-small cell lung cancer cells proliferation by targeting
      EGFL7.
AB  - MicroRNAs (miRNAs) represent an abundant group of small non-coding RNAs that
      regulate gene expression, and have been demonstrated to play roles as tumor
      suppressor genes (oncogenes), and affect homeostatic processes such as
      development, cell proliferation, and cell death. Subsequently, epidermal growth
      factor-like domain 7 (EGFL7), which is confirmed to be involved in cellular
      responses such as cell migration and blood vessel formation, is identified as a
      potential miR-126 target by bioinformatics. However, there is still no evidence
      showing EGFL7's relationship with miR-126 and the proliferation of lung cancer
      cells. The aim of this work is to investigate whether miR-126, together with
      EGFL7, have an effect on non-small cell lung cancer (NSCLC) cells' proliferation.
      Therefore, we constructed overexpressed miR-126 plasmid to target EGFL7 and
      transfected them into NSCLC cell line A549 cells. Then, we used methods like
      quantitative RT-PCR, Western blot, flow cytometry assay, and immunohistochemistry
      staining to confirm our findings. The result was that overexpression of miR-126
      in A549 cells could increase EGFL7 expression. Furthermore, the most notable
      finding by cell proliferation related assays is that miR-126 can inhibit A549
      cells proliferation in vitro and inhibit tumor growth in vivo by targeting EGFL7.
      As a result, our study demonstrates that miR-126 can inhibit proliferation of non
      small cell lung cancer cells through one of its targets, EGFL7.

PMID- 20034473
TI  - Lanford medium induces high quality hepatic lineage cell differentiation directly
      from mouse embryonic stem cell-derived mesendoderm.
AB  - To establish an effective induction method for hepatic differentiation using
      serum-free media, the effects of activin in serum-containing and serum-free
      conditions on embryoid body (EB) induction into mesendoderm were investigated by
      Western blot analysis and real-time reverse transcription-polymerase chain
      reaction (RT-PCR) as a first step. The expression of P-smad2 and mesendodermal
      markers was markedly enhanced by 100ng/ml activin under serum-free conditions but
      were inhibited or masked under serum-containing conditions. Next, serum-free
      Lanford medium was used to attempt the direct induction of activin-treated EBs
      expressing mesendodermal markers into hepatic lineage cells and this induction
      was compared to that induced using Iscove's Modified Dulbecco's medium containing
      20% fetal bovine serum. Once immersed in the Lanford medium, EBs began to show
      typical hepatic features by day 17, including Alb, AFP, TTR, and AAT expression
      detected by RT-PCR, and ALB, AFP, and CK18 expression detected by immunostaining.
      On day 22, these cells were of high quality characterized by the expression of
      metabolizing enzymes, including Ugt1a1, Slcola4, cyp3a11, cyp2b10, and cyp7a1
      detected by real-time PCR, a 50-fold greater cyp3A11 response than control to
      100muM dexamethasone stimulation, specific cellular uptake of indocyanine green,
      and glycogen storage in the cytoplasm. These results indicate that this simple
      two-step induction method under serum-free conditions induces hepatic lineage
      cells with high quality directly from mouse embryonic stem (ES) cell-derived
      mesendoderm.

PMID- 20034474
TI  - Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer
      activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human
      cancer cells.
AB  - Microtubule is a popular target for anticancer drugs. Chamaecypanone C, is a
      natural occurring novel skeleton compound isolated from the heartwood of
      Chamaecyparis obtusa var. formosana. The present study demonstrates that
      chamaecypanone C induced mitotic arrest through binding to the colchicine-binding
      site of tubulin, thus preventing tubulin polymerization. In addition, cytotoxic
      activity of chamaecypanone C in a variety of human tumor cell lines has been
      ascertained, with IC(50) values in nanomolar ranges. Flow cytometric analysis
      revealed that chamaecypanone C treated human KB cancer cells were arrested in
      G(2)-M phases in a time-dependent manner before cell death occurred. Additional
      studies indicated that the effect of Chamaecypanone C on cell cycle arrest was
      associated with an increase in cyclin B1 levels and a mobility shift of
      Cdc2/Cdc25C. The changes in Cdc2 and Cdc25C coincided with the appearance of
      phosphoepitopes recognized by a marker of mitosis, MPM-2. Interestingly, this
      compound induced apoptotic cell death through caspase 8-Fas/FasL dependent
      pathway, instead of mitochondria/caspase 9-dependent pathway. Notably, several KB
      derived multidrug resistant cancer cell lines overexpressing P-gp170/MDR and MRP
      were sensitive to Chamaecypanone C. Taken together, these findings indicated that
      Chamaecypanone C is a promising anticancer compound that has potential for
      management of various malignancies, particularly for patients with drug
      resistance.

PMID- 20034475
TI  - Effects of age and retinal degeneration on the expression of proprotein
      convertases in the visual cortex.
AB  - Proprotein convertases (PCs) comprise a large family of subtilisin-like,
      eukaryotic, serine endoproteases that process substrates important in the
      development, homeostasis, and pathology of the nervous system. Despite important
      interactions with these substrates, including neurotrophins, PC expression
      throughout normal postnatal development and disease progression in the brain
      remains unknown. The primary objective of this study was to determine whether the
      expression profiles of widely expressed and tissue-specific PCs varied during
      normal brain development or neurological disorders. We examined the expression of
      mRNAs for seven PCs in the visual cortex of normal and visually impaired mice at
      10 postnatal developmental time points between Week 1 and Week 35. Widely
      expressed PCs (furin, PACE4, PC5, and PC7) all exhibited a similar expression
      profile. High mRNA levels were seen at Week 1 with levels generally lower over
      the next 5-6 weeks. In visually impaired mice, widely expressed PCs again all
      exhibited a similar expression profile, but it was dramatically different than
      observed in normal mice. The temporal expression of tissue-specific PCs varied in
      wild-type mice. Interestingly, this variability was sharply reduced in visually
      impaired mice. Overall, these data suggest a timetable of altered PC expression
      that corresponds closely with the formation of functional visual maps in the
      visual cortex. The implications of these findings are discussed in the context of
      neurotrophin processing and synaptogenesis in the developing visual cortex.

PMID- 20034476
TI  - Effects of ubiquinone on hydroperoxide concentration and antioxidant enzymatic
      activities in the rat hippocampus during pilocarpine-induced seizures.
AB  - Recent researches have shown that antioxidant compounds may have certain
      neuroprotective effect against the neurotoxicity of seizures at cellular level.
      Ubiquinone (UQ), an antioxidant compound, exhibits a wide range of therapeutic
      effects that are attributed to its potent antioxidant capacity. The objective of
      the present study was to evaluate the neuroprotective effects of UQ in rats,
      against the observed oxidative stress during seizures induced by pilocarpine.
      Wistar rats were treated with either 0.9% saline (i.p., control group), UQ (5, 10
      or 20 mg/kg, i.p., UQ5, UQ10 and UQ20 groups), pilocarpine (400 mg/kg, i.p., P400
      group), or co-administration of pilocarpine with UQ group rats 30 min prior to UQ
      administration. After the treatments all groups were observed for 24 h. The
      antioxidant enzymatic activities as well as the hydroperoxide concentrations were
      measured using spectrophotometric methods and the results were analyzed. In
      pilocarpine group there was a significant increase in hydroperoxides
      concentration and glutathione peroxidase activity. However, no alteration was
      observed in superoxide dismutase and catalase activities. Antioxidant treatment
      significantly reduced the hydroperoxide content and increased the superoxide
      dismutase, catalase and glutathione peroxidase activities in rat hippocampus
      during seizures induced by pilocarpine. Our findings strongly support the
      hypothesis that oxidative stress in hippocampus occurs during seizures induced by
      pilocarpine, which indicates that brain damage induced by the oxidative process
      plays a crucial role in seizures pathogenic consequences. Our result also
      suggests that ubiquinone can exert significant neuroprotective effects that might
      be useful in the treatment of neurodegenerative diseases.

PMID- 20034478
TI  - High glucose enhances intracellular Ca2+ responses triggered by purinergic
      stimulation in retinal neurons and microglia.
AB  - Activation of purinergic P2 receptors, which are expressed in neurons and
      microglial cells, normally induces an increase in intracellular calcium
      concentration ([Ca(2+)](i)) and some of the inflammatory mediators and excitatory
      neurotransmitters found to be implicated in neuronal cell death observed in
      diabetic retinas are released in response to an increase in the [Ca(2+)](i).
      However, it is unknown whether hyperglycemia/high glucose has an effect in the
      [Ca(2+)](i) changes triggered by the activation of P2 receptors in retinal cells.
      Using single-cell calcium imaging studies, we found that [Ca(2+)](i) changes
      triggered by purinergic receptors activation, both in retinal neurons and
      microglial cells, were potentiated in cells that had been cultured in high
      glucose conditions. In retinal neurons the increase in [Ca(2+)](i) was mostly due
      to Ca(2+) influx through voltage sensitive calcium channels, whereas in
      microglial cells Ca(2+) influx occurred mainly through P2X receptor channels,
      while there was also a smaller component of [Ca(2+)](i) rise dependent on calcium
      release from intracellular stores, probably due to P2Y receptor activation. In
      conclusion, our results show that rat retinal neural cells cultured in high
      glucose conditions show increased calcium responses to P2 receptors activation.
      This augmented calcium response might account for the increase in the release of
      neurotransmitters and inflammatory mediators found in diabetic retinas and,
      therefore, be responsible for retinal cell death observed in the early stages of
      diabetic retinopathy.

PMID- 20034479
TI  - Presenilin 1-related alterations in DNA integrity in a transgenic mouse model of
      Alzheimer's disease.
AB  - The present study tested the hypothesis that mutations in amyloid precursor
      protein (APP) and presenilin (PS) 1 result in alterations in the amount of
      nuclear (n) DNA repair and nDNA damage in neurons in vivo. To this end, the
      relative amount of nDNA repair was measured in 8-month-old transgenic mice
      expressing either human mutant APP (APP751(SL) mice), human mutant PS1
      (PS1(M146L) mice) or both human mutant APP and PS1 (APP751(SL)/PS1(M146L) mice)
      with unscheduled DNA synthesis, and the relative amount of nDNA single strand
      breaks (SSB) with in situ nick translation. APP751(SL)/PS1(M146L) mice showed a
      significantly decreased relative amount of nDNA repair in pyramidal cells in
      hippocampal area CA1/2 compared to APP751(SL) mice. Furthermore, PS1(M146L) mice
      showed a significantly increased relative amount of nDNA SSB in both granule
      cells in the dentate gyrus and pyramidal cells in area CA1/2 compared to both
      APP751(SL) mice and APP751(SL)/PS1(M146L) mice. These results might indicate a
      previously unknown action of mutations in PS1 on DNA integrity, which might be
      involved in the pathophysiologic processes of mutant PS1 in Alzheimer's disease.

PMID- 20034477
TI  - Orexin mediates morphine place preference, but not morphine-induced hyperactivity
      or sensitization.
AB  - Orexin (or hypocretin) has been implicated in mediating drug addiction and
      reward. Here, we investigated orexin's contribution to morphine-induced
      behavioral sensitization and place preference. Orexin-/- (OKO) mice and
      littermate wild-type (WT) controls (n=56) and C57BL/6J mice (n=67) were tested
      for chronic morphine-induced locomotor sensitization or for conditioned place
      preference (CPP) for a morphine- or a cocaine-paired environment. C57BL/6J mice
      received the orexin receptor 1 (Ox1r) antagonist, SB-334867, prior to test
      sessions. OKO mice did not significantly differ from WT controls in locomotor
      activity following acute- or chronic-morphine treatments. Similarly, mice treated
      with the Ox1r antagonist did not differ from vehicle controls in locomotor
      activity following acute- or chronic-morphine treatments. In contrast, while OKO
      mice did not differ from WT controls in preference for a morphine-paired
      environment, the Ox1r antagonist significantly attenuated place preference for a
      morphine-, but not a cocaine-paired, environment. These data suggest that orexin
      action is not required for locomotor responses to acute and chronic morphine, but
      Ox1r signaling can influence morphine-seeking in WT animals.

PMID- 20034480
TI  - Sensitivity to seizure-like activity in Drosophila following acute hypoxia and
      hypercapnia.
AB  - Human seizure disorders represent a heterogeneous collection of neuropathies,
      many of which are poorly understood. To investigate the etiology of seizure
      disorders, we have used a group of Drosophila mutants known as the bang-sensitive
      (BS) paralytics. The BS mutants exhibit seizure-like activity (SLA) following a
      wide variety of insults including mechanical shock, electrical shock, high
      frequency light and cold temperatures. In this study, we show that two novel
      insults, hypoxia and hypercapnia (elevated CO(2) levels) are potent triggers of
      SLA in a number of the BS mutants. We also show that both of these insults,
      hypoxia and hypercapnia, can trigger SLA in wild-type flies as well. However, we
      find that the BS mutants are more susceptible than wild-type flies to these
      insults as they exhibit more SLA following these insults and, in the case of
      hypercapnia, they exhibit SLA at a lower threshold. In addition, we demonstrate
      that the BS mutants are more susceptible to the anesthetizing effects of CO(2) as
      compared to wild-type flies. The increased sensitivity to both hypoxia and
      hypercapnia in these BS mutants suggests possible physiological defects that may
      underlie seizure susceptibility.

PMID- 20034481
TI  - Optimal performance in a countermanding saccade task.
AB  - Countermanding an action is a fundamental form of cognitive control. In a saccade
      countermanding task, subjects are instructed that, if a stop signal appears
      shortly after a target, they are to maintain fixation rather than to make a
      saccade to the target. In recent years, recordings in the frontal eye fields and
      superior colliculus of behaving non-human primates have found correlates of such
      countermanding behavior in movement and fixation neurons. In this work, we extend
      a previous neural network model of countermanding to account for the high pre
      target activity of fixation neurons. We propose that this activity reflects the
      functioning of control mechanisms responsible for optimizing performance. We
      demonstrate, using computer simulations and mathematical analysis, that pre
      target fixation neuronal activity supports countermanding behavior that maximizes
      reward rate as a function of the stop signal delay, fraction of stop signal
      trials, intertrial interval, duration of timeout, and relative reward value. We
      propose experiments to test these predictions regarding optimal behavior.

PMID- 20034482
TI  - Short-term language experience shapes the plasticity of the visual word form
      area.
AB  - Previous studies have identified a region in the left fusiform gyrus that
      responds selectively to visual words, termed the visual word form area (VWFA).
      Converging evidence from neuropsychological, electrophysiological, and functional
      neuroimaging studies suggests that the VWFA is wired up largely by long-term
      experience because it responds specifically to words and letter strings only in
      an orthography a subject knows. However, it is less clear whether the plasticity
      of the VWFA can be modulated by short-term language experience. Here, we used
      functional magnetic resonance imaging (fMRI) to address this question by
      examining whether the representation for novel stimuli could be constructed in
      the VWFA after a short-term language experience. In particular, we trained
      subjects to associate a set of novel stimuli with English letters. We found that
      VWFA response to the trained stimuli was significantly higher than that of
      untrained stimuli after 3 days of association training. This learning-induced
      change in neural activities was absent in other specialized cortical areas
      involved in face perception or in processing object shapes. Multivariate pattern
      analysis further revealed that the learning-induced representation engaged the
      same neural population underlying the representation for language forms
      constructed through long-term experience. Our study clearly illuminates that the
      plasticity of the VWFA can be shaped by short-term language experience, bridging
      the gap between short-term and long-term experiences in language learning.

PMID- 20034483
TI  - Apolipoprotein E protects cultured pericytes and astrocytes from D-Abeta(1-40)
      mediated cell death.
AB  - Cerebral amyloid angiopathy (CAA) is a common pathological finding in Alzheimer's
      disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type; in
      this latter condition it is caused by deposition of mutated amyloid beta protein
      (Abeta Glu22Gln; D-Abeta(1-40)). Previously, we found a dependence of the Abeta
      mediated toxicity and apolipoprotein E (apoE) production by cultured pericytes on
      apoE genotype. Given their close association with the cerebrovascular wall both
      astrocytes and pericytes may be involved in CAA development, a process that
      includes Abeta deposition and clearance and that may be affected by interaction
      with locally produced apolipoprotein E (apoE). Although astrocytes are regarded
      as the major source of apolipoprotein E (apoE) in the brain, also pericytes
      produce apoE. In this study we compared the apoE production capacity, the effects
      of apoE on D-Abeta(1-40) internalization, D-Abeta(1-40) cell surface accumulation
      and the vulnerability for D-Abeta(1-40)-induced toxicity of either cell type in
      order to quantify the relative contributions of astrocytes and pericytes in the
      various processes that contribute to CAA formation. Strikingly, cultured
      astrocytes produced only 3-10% of the apoE amounts produced by pericytes.
      Furthermore, pericytes with the apoE epsilon4 allele produced three times less
      apoE and were more vulnerable to D-Abeta(1-40) treatment than pericytes without
      an epsilon4 allele. Such relations were not observed with astrocytes in vitro.
      Both pericytes and astrocytes, however, were protected from Abeta-induced
      cytotoxicity by high levels of pericyte-derived apoE, but not recombinant apoE.
      In addition, pericyte-derived apoE dose-dependently decreased both
      internalization of Abeta and Abeta accumulation at the cell surface in either
      cell type. The present data suggest that apoE produced by pericytes, rather than
      astrocyte-produced apoE, modulates Abeta cytotoxicity and Abeta removal near the
      vasculature in the brain. Furthermore, since apoE production in pericytes is
      genotype dependent, this may contribute to the apoE genotype-dependent
      development of CAA in vivo.

PMID- 20034484
TI  - Peripheral blood effects in benzene-exposed workers.
AB  - The hematotoxic effects of benzene exposure may be important in the occurrence of
      subsequent health effects. We sought to provide further information on peripheral
      blood effects by studying 928 workers in five factories in and around Shanghai,
      China exposed to a wide range of benzene concentrations. Specifically, we sought
      to investigate which blood indices are more strongly related to benzene exposure
      and which concentration levels of benzene result in peripheral blood changes.
      Lifestyle habits and demographic information was obtained via questionnaire, and
      potentially important genetic influences were determined by assessing single
      nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene
      exposure estimated from individual monitoring results ranged from 0.07 to 872
      mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were
      examined. Stronger effects on peripheral blood were seen for red cell indices
      such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The
      most sensitive parameters to benzene appeared to be neutrophils and the mean
      platelet volume (MPV), where effects were seen for benzene air concentrations of
      7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood
      effects, pointing to the need to scrutinize levels of both compounds in the
      occupational environment.

PMID- 20034485
TI  - Topoisomerase II inhibition by the bioactivated benzene metabolite hydroquinone
      involves multiple mechanisms.
AB  - While benzene is widely recognized as a human and animal carcinogen, the key
      mechanisms underlying its carcinogenic effects remain unknown. Inhibition of
      topoisomerase II (topoII) by benzene and its metabolites represents a potential
      mechanism by which benzene could induce its chromosome-altering and leukemogenic
      effects. Previous work from our laboratory and others has demonstrated that
      bioactive benzene metabolites are capable of inhibiting topoII in isolated enzyme
      and cell culture systems. Similarly, a decrease in topoII activity has been seen
      in the bone marrow of mice administered benzene in vivo. The objective of these
      studies was to further investigate the mechanisms by which the bioactivated
      benzene metabolite, hydroquinone (BAHQ), inhibits topoII in vitro, and to
      identify the point(s) in the enzyme's catalytic cycle where inhibition occurs.
      Our experiments indicate that BAHQ inhibits topoII at the DNA binding stage as
      well as in the closed clamp stage in the catalytic cycle, thereby interfering
      with either the binding to, or the release of, DNA from the enzyme. While
      increases in the cleavable complex were also seen with BAHQ treatment, our
      results suggest that this is related to a shift in equilibrium due to an
      accumulation of the topoII enzyme at the closed clamp stage rather than a major
      inhibitory effect on the religation step. An increase in cleavable complex
      formation as well as the inhibition of enzymatic activity at the closed clamp and
      other stages of the catalytic cycle in bone marrow cells would likely result in
      DNA breakage, the formation of chromosomal aberrations, and could potentially
      result in leukemia-associated chromosomal translocations, similar to those seen
      in leukemias induced by the bisdioxopiperazine type of catalytic topoII
      inhibitors.

PMID- 20034486
TI  - Role of hydroquinone-thiol conjugates in benzene-mediated toxicity.
AB  - Hydroquinone (HQ) is a metabolite of benzene, and in combination with phenol
      (PHE), reproduces benzene myelotoxicity. HQ readily oxidizes to 1,4-benzoquinone
      (1,4-BQ) followed by the reductive addition of glutathione (GSH). Subsequent
      cycles of oxidation and GSH addition give rise to a variety of mono-, and multi
      GSH substituted conjugates. Following administration of PHE/HQ (1.1 mmol/kg/0.9
      mmol/kg, ip) to male Sprague-Dawley (SD) rats, 2-(glutathion-S-yl)HQ [GS-HQ], 2,5
      bis-(glutathion-S-yl)HQ [2,5-GS-HQ], 2,6-bis-(glutathion-S-yl)HQ [2,6-GS-HQ], and
      2,3,5-tris-(glutathion-S-yl)HQ [2,3,5-GS-HQ] were all identified in bone marrow.
      2-(Cystein-S-ylglycine)HQ [2-(CysGly)HQ], 2-(cystein-S-yl)HQ [2-(Cys)HQ], and 2
      (N-acetylcystein-S-yl)HQ [2-(NACys)HQ] were also found in the bone marrow of
      PHE/HQ and benzene treated rats and mice, indicating the presence of an active
      mercapturic acid pathway within bone marrow. Moreover, 2,6-GS-HQ and 2,3,5-GS-HQ
      were hematotoxic when administered to rats. All of the HQ-GSH conjugates retain
      the ability to redox cycle and generate reactive oxygen species (ROS), and to
      arylate target proteins. Recent in vitro and in vivo studies in our laboratory
      revealed lysine and arginine residues as primary targets of 1,4-BQ, GS-HQ and 2
      (NACys)HQ adduction. In contrast 1,4-BQ-adduction of cysteine residues may be a
      transient interaction, where physiological conditions dictate adduct stability.
      The generation of ROS and alkylation of proteins may both contribute to benzene
      mediated myelotoxicity, and the two processes may be inter-dependent. However,
      the precise molecular mechanism by which benzene and HQ-GSH conjugates induce
      hematotoxicity remains to be determined. Within 18h of administration of PHE/HQ
      to SD rats a significant decrease in blood lymphocyte count was observed. At this
      early time point, erythrocyte counts and hemoglobin concentrations remained
      within the normal range. Concomitant with the decrease in lymphocyte count,
      western blot analysis of bone marrow lysate, using HQ-GSH and 4-hydroxy-2-nonenal
      (4HNE) specific antibodies, revealed the presence of HQ-GSH- and 4HNE-derived
      protein adducts. Identification of these adducts is required before the
      functional significance of such protein modifications can be determined.

PMID- 20034487
TI  - Fish oil supplementation decreases serum soluble receptor activator of nuclear
      factor-kappa B ligand/osteoprotegerin ratio in female patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL)
      to osteoprotegerin ratio is designated as a bone metabolism equation in many
      rheumatologic disorders and would be modified with fish oil (FO) supplementation.
      DESIGN AND METHODS: Eighty-three females with rheumatoid arthritis were divided
      randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months
      accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor
      necrosis factor alpha (TNFalpha) serum levels were measured before and after
      treatment. RESULTS: Serum levels of osteoprotegerin increased, although sRANKL,
      TNFalpha and sRANKL/osteoprotegerin ratio decreased with FO therapy. A
      significant positive correlation was observed between sRANKL/osteoprotegerin
      ratio and TNFalpha levels (r=0.327, p=0.040) in the FO-treated group.
      CONCLUSIONS: FO could decrease the inflammatory response by lowering of serum
      TNFalpha levels and sRANKL/osteoprotegerin ratio.

PMID- 20034489
TI  - Interactions between Notch- and hypoxia-induced transcriptomes in embryonic stem
      cells.
AB  - Interaction between key signaling mechanisms is important to generate the
      diversity in signaling output required for proper control of cellular
      differentiation and function, although the molecular manifestations of such cross
      talk are only partially understood. Notch signaling and the cellular response to
      hypoxia intersect at different points in the signaling cascades, and in this
      report we analyze the consequences of this cross-talk at the transcriptome level.
      Mouse ES cells were subjected to various combinations of hypoxia and/or activated
      Notch signaling, and the transcriptome changes could be grouped into different
      categories, reflecting various modes of hypoxia and Notch signaling integration.
      Two principal categories of novel Notch- and hypoxia-induced genes were
      identified: (i) a larger set of Notch or hypoxic target genes which were induced
      by one pathway and not significantly affected by the activity status of the other
      pathway and (ii) a smaller set of genes co-regulated by Notch and hypoxia. In the
      latter category, we identified genes that were induced by hypoxia and the
      expression of which was enhanced by active Notch signaling and another group of
      genes that were induced by Notch and hypoxia independently. Several of the
      hypoxia- and Notch-induced genes were found to be upregulated in various forms of
      cancer. Identification of genes co-regulated by the two pathways may provide a
      molecular platform to better understand the intersection between the two
      signaling cascades in normal development and cancer.

PMID- 20034488
TI  - Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism for
      aneuploidy in cancer.
AB  - In mitosis, the duplicated chromosomes are separated and equally distributed to
      progeny cells under the guidance of the spindle, a dynamic microtubule network.
      Previous studies revealed a mitotic checkpoint that prevents segregation of the
      chromosomes until all of the chromosomes are properly attached to microtubules
      through the kinetochores. A variety of kinetochore-localized proteins, including
      Mad2 and Cdc20, have been implicated in controlling the mitotic checkpoint. Here
      we report that both Mad2 and Cdc20 can physically associate with Nek2, a
      serine/threonine kinase implicated in centrosome functions. We show that, similar
      to Nek2, the endogenous Cdc20 protein can be detected in the centrosome and the
      spindle poles. Both Cdc20 and Mad2 can be phosphorylated by Nek2. Moreover, our
      studies demonstrate that overexpression of Nek2 enhances the ability of Mad2 to
      induce a delay in mitosis. These observations indicate that Nek2 may act upon the
      Mad2-Cdc20 protein complex and play a critical role in regulating the mitotic
      checkpoint protein complex. We propose that overexpression of Nek2 may promote
      aneuploidy by disrupting the control of the mitotic checkpoint.

PMID- 20034490
TI  - Acanthamoeba castellanii: cellular changes induced by chlorination.
AB  - Chlorination is a well-known disinfection method, used in water treatment to
      inactivate various microorganisms, it induces numerous cellular changes. Even
      though Acanthamoebae are frequently found in water, the cellular changes induced
      in Acanthamoebae have not been described in the literature. Acanthamoebae are
      pathogenic amoebae and may provide a reservoir for pathogenic bacteria such as
      Legionellapneumophila; it is consequently important to understand the response of
      this amoeba to chlorination, and our study was indeed aimed at examining cellular
      changes in Acanthamoebae following chlorination. Acanthamoeba trophozoites were
      treated at various chlorine concentrations (1-5mg/L). A 3-log reduction in
      Acanthamoebae population was achieved with 5mg/L of free chlorine. Confocal
      microscopy and flow cytometry experiments indicated that chlorination induced
      cell permeabilization, size reduction and likely intracellular thiol
      concentration. Our data show that among the non-cultivable cells some remained
      impermeabilized (negative staining with propidium iodide), thereby suggesting
      that these cells might remained viable. A similar state is described in other
      microorganisms as a VBNC (viable but not cultivable) state. Electron microscopy
      observations illustrate drastic morphological changes: the pseudopods disappeared
      and subcellular components, such as mitochondrion, were pronouncedly affected. In
      conclusion, depending on the concentration used, chlorination leads to many
      cellular effects on Acanthamoeba that could well arise in cell inactivation.

PMID- 20034491
TI  - Trypanosoma rangeli: differential expression of ecto-phosphatase activities in
      response to inorganic phosphate starvation.
AB  - In this work, we showed that living cells of Trypanosoma rangeli express
      different ecto-phosphatase activities in response to different inorganic
      phosphate (Pi) concentrations in the culture medium. The ecto-phosphatase
      activity from T. rangeli grown at low-Pi concentration was inhibited by the
      increase of the pH, while the ecto-phosphatase of the cells grown at high Pi
      concentration was not modulated by the change of the pH of the medium. Okadaic
      acid inhibited only the ecto-phosphatase activity from cells grown at low-Pi
      concentration but not the ecto-phosphatase activity from cells grown at high-Pi
      concentration. Accordingly, phosphatase activity from T. rangeli grown at low Pi
      concentration was able to hydrolyze P-serine and P-threonine at high rate but not
      P-tyrosine. The phosphatase activity from T. rangeli grown at high-Pi
      concentration was able to hydrolyze P-serine, P-threonine and P-tyrosine with the
      same rate. The addition of anterior midgut homogenate of Rhodnius prolixus on the
      epimastigotes suspension inhibited the enzyme activity of T. rangeli grown at low
      Pi concentration. On the other hand, anterior midgut homogenate had no effect in
      the ecto-phosphatase of T. rangeli maintained at high-Pi concentration.
      Altogether, the results described here indicate that ecto-phosphatase activities
      hydrolyzing phosphorylated compounds present in the extracellular medium of T.
      rangeli are regulated by the external Pi concentration.

PMID- 20034492
TI  - Brugia malayi: in vitro effects of ivermectin and moxidectin on adults and
      microfilariae.
AB  - The effect of ivermectin and moxidectin on the motility of Brugia malayi adults
      and microfilariae and on the fertility of B. malayi females was examined.
      Motility was reduced in adults after exposure to both drugs and worms were non
      motile and dead within eight days. The motility of microfilariae was
      significantly reduced at all drug concentrations and ceased at concentrations of
      2500 and 5000mug/mL. The motility of microfilariae released by females was
      reduced after exposure to both drugs, however ivermectin had a greater effect at
      concentrations between 170 and 5000mug/mL. Both drugs reduced the number of
      microfilariae released by females and within four days their release was
      inhibited. The presence of the bacterial endosymbiont Wolbachia was examined in
      adults and microfilariae after exposure to increasing concentrations of
      ivermectin and moxidectin. A decrease in wsp expression was correlated with
      increasing drug concentration.

PMID- 20034493
TI  - Eimeria tenella: cloning and characterization of telomerase reverse transcriptase
      gene.
AB  - Telomerase is essential for maintaining telomere length and chromosome stability
      in most eukaryotic organisms. The telomerase ribonucleoprotein complex consists
      of two essential components, the intrinsic telomerase RNA and the catalytic
      telomerase reverse transcriptase protein. Here we describe the cloning,
      sequencing and characterization of the telomerase reverse transcriptase catalytic
      subunit from the apicomplexan protozoon Eimeria tenella. The amino acid sequence
      predicted from it has all the signature motifs of the TERT family members. The E.
      tenella TERT cDNA contains an open reading frame encoding a protein with 1497
      amino acids predicted size of 172kDa and isoelectric point of 9.344. It contains
      the conserved reverse transcriptase motifs 1, 2, A, B, C, D and E as well as the
      TERT-specific T motif and the N-terminal conserved motifs GQ, CP and QFP. RT-PCR
      analysis indicated that E. tenella TERT mRNA expressed in sporozoites and
      merozoites phase while not in unsporulated oocysts. At the same time, the result
      of TRAP assay indicated that marked telomerase activity were detected in
      sporozoites and merozoites. In contrast, telomerase activity was not detected in
      unsporulated oocysts.

PMID- 20034494
TI  - Mechanical stimulation suppresses phosphorylation of eIF2alpha and PERK-mediated
      responses to stress to the endoplasmic reticulum.
AB  - Cellular perturbations such as stress to the endoplasmic reticulum induce an
      integrated stress response, which activates phosphorylation of eIF2alpha and
      leads to alleviation of cellular injury or apoptosis. This study investigated the
      role of mechanical stimulation in the regulation of eIF2alpha and cell death.
      Mechanical stimulation was applied to mouse ulnae, MC3T3 cells, and mesenchymal
      stem cells. The results demonstrate that mechanical stimulation reduces
      phosphorylation of eIF2alpha through inactivation of Perk. Furthermore, flow pre
      treatment reduces thapsigargin-induced cell mortality through suppression of
      phosphorylation of Perk. However, H(2)O(2)-driven cell mortality, which is not
      mediated by Perk, is not suppressed by mechanical stimulation. Taken together,
      our observations suggest a pro-survival role of mechanical stimulation in Perk
      mediated stress responses.

PMID- 20034495
TI  - Women's interest in visual sexual stimuli varies with menstrual cycle phase at
      first exposure and predicts later interest.
AB  - This study investigated whether women's interest in visual sexual stimuli varied
      with their hormonal state. Viewing times of 30 women, 15 normal cycling (NC) and
      15 oral contracepting (OC), to sexually explicit photos were measured at three
      different times. NC women were tested during their menstrual, periovulatory, and
      luteal phases, and OC women were tested at equivalent temporal intervals.
      Subjects viewed stimuli as long as desired, thus viewing time measured subject
      interest. Subjective ratings of stimulus sexual attractiveness were obtained on
      each test. There was no overall relationship between menstrual cycle phase and
      viewing time. However the participant's menstrual cycle phase during first
      exposure to sexual stimuli predicted subsequent interest in sexual stimuli during
      the next two tests. NC women who first viewed stimuli during their periovulatory
      phase looked longer at the sexual stimuli across all sessions than did women
      first tested in their luteal phase. OC women first exposed to the sexual stimuli
      during menstruation looked longer at the stimuli across all sessions than did OC
      women first exposed at other test phases. Neither current test phase nor initial
      cycle phase influenced subjective ratings. Women had increased interest in sexual
      stimuli across all sessions if first exposed to sexual stimuli when endogenous
      estrogens were most likely highest. These data suggest that women's interest in
      visual sexual stimuli is modulated by hormones such that the hormonal condition
      at first exposure possibly determines the stimuli's emotional valence, markedly
      affecting subsequent interest in sexual stimuli.

PMID- 20034496
TI  - Characterization and expression of cry4Cb1 and cry30Ga1 from Bacillus
      thuringiensis strain HS18-1.
AB  - We characterized a novel Bacillus thuringiensis isolate native to China (HS18-1)
      that shows a spherical crystal harboring two major proteins of about 70 and
      130kDa, and contains three novel cry genes (cry4Cb1, cry30Ga1, cry54-type).
      Furthermore, the cry4Cb1 and cry30Ga1 genes were expressed in Escherichia coli
      BL21 (DE3): pLysS. Insecticidal activity tests showed that the cry4Cb1 protein
      exhibited larvicidal activity against Aedes aegypti (Diptera) and the cry30Ga1
      protein was toxic to both A. aegypti and P. xylostella (Lepidoptera).

PMID- 20034497
TI  - Histological survey of symbionts and other conditions in razor clam Ensis
      arcuatus (Jeffreys, 1865) (Pharidae) of the coast of Galicia (NW Spain).
AB  - Symbionts and abnormal conditions of razor clam Ensis arcuatus were surveyed in
      three commercially important natural beds of Galician estuaries (NW Spain).
      Samples of 15-20 E. arcuatus were collected every 2 months from January 2003
      until July 2004 and processed for histological examination. Prokaryote-like
      colonies, renal coccidians, gregarines, Trichodina sp. ciliates, haplosporidian
      like plasmodia, turbelaria, trematode metacercariae, cestode-like larvae and
      basophilic inclusion bodies were observed in razor clam tissues without causing
      host damage. Bucephalid digenean sporocysts and germinoma were seen in some
      samples causing moderate or severe damage to the host depending on the intensity
      of infection and both could be a cause for concern if prevalence reached
      epizootic levels in Galician E. arcuatus populations. None of the parasites
      detected is OIE notifiable and, in general, the commercially exploited beds
      studied seem to be devoid of serious pathogens.

PMID- 20034498
TI  - Selection for fitness at the individual or population levels: modelling effects
      of genetic modifications in microalgae on productivity and environmental safety.
AB  - A mechanistic model of microalgae is used to explore the implications of
      modifying microalgal chlorophyll content and photosynthetic efficiency with an
      aim to optimising commercial biomass production. The models show the potential
      for a 10 fold increase in microalgae productivity in genetically modified versus
      unmodified configurations, while also enabling the use of bioreactors of greater
      optical depth operating at lower dilution rates. Analysis suggests that natural
      selection of a trait benefiting the individual (high Chl:C(max), i.e., high
      antennae size) conflicts with artificial selection of a trait (low Chl:C(max)) of
      most benefit to production at the population level. The implication is that GM
      strains rather than strains selected from nature will be most beneficial for
      commercial algal biofuels production. Further, escaped GM algae populations may,
      depending on the specific nature of the modification, be quickly out-competed by
      the natural forms because individually a high Chl:C is beneficial in low light
      environments. However, it remains possible that changes in biochemical
      composition associated with genetic modification of photosystem competence, or
      with other selection processes to enhance commercial gain, may adversely affect
      the value of such organisms as prey for zooplankton, leading to the unwanted
      generation of future harmful algae.

PMID- 20034500
TI  - The origin of the biologically coded amino acids.
AB  - Biology uses essentially 20 amino acids for its coded protein enzymes,
      representing a very small subset of the structurally possible set. Most models of
      the origin of life suggest organisms developed from environmentally available
      organic compounds. A variety of amino acids are easily produced under conditions
      which were believed to have existed on the primitive Earth or in the early solar
      nebula. The types of amino acids produced depend on the conditions which
      prevailed at the time of synthesis, which remain controversial. The selection of
      the biological set is likely due to chemical and early biological evolution
      acting on the environmentally available compounds based on their chemical
      properties. Once life arose, selection would have proceeded based on the
      functional utility of amino acids coupled with their accessibility by primitive
      metabolism and their compatibility with other biochemical processes. Some
      possible mechanisms by which the modern set of 20 amino acids was selected
      starting from prebiotic chemistry are discussed.

PMID- 20034499
TI  - Interpreting the effect of vaccination on steady state infection in animals
      challenged with Simian immunodeficiency virus.
AB  - A representative vaccinated macaque challenged with SIVmac251 establishes a
      persistent infection with a lower virus load, higher CTL frequencies, and much
      higher helper cell frequencies, than a representative control animal. The reasons
      for the difference are not fully understood. Here we interpret this effect using
      a mathematical model we developed recently to explain results of various
      experiments on virus and CTL dynamics in SIV-infected macaques and HIV-infected
      humans. The model includes two types of cytotoxic lymphocytes (CTLs) regulated by
      antigen-activated helper cells and directly by infected cells, respectively, and
      predicts the existence of two steady states with different viremia, helper cell
      and CTL levels. Depending on the initial level of CTL memory cells and helper
      cells, a representative animal ends up in either the high-virus state or the low
      virus state, which accounts for the observed differences between the two animal
      groups. Viremia in the low-virus state is proportional to the antigen sensitivity
      threshold of helper cells. Estimating the infectivity ratio of activated and
      resting CD4 T cells at 200-300, the correct range for the critical memory cell
      percentage and the viremia peak suppression is predicted. However, the model does
      not explain why viremia in the "low-virus state" is surprisingly high , relative
      to vaccinated animals infected with SHIV, and broadly distributed among
      challenged animals. We conclude that the model needs an update explaining
      extremely low sensitivity of uninfected helper cells to antigen in vaccinated
      animals.

PMID- 20034501
TI  - The basic reproductive ratio of life.
AB  - Template-directed polymerization of nucleotides is believed to be a pathway for
      the replication of genetic material in the earliest cells. We assume that
      activated monomers are produced by prebiotic chemistry. These monomers can
      undergo spontaneous polymerization, a system that we call "prelife." Adding
      template-directed polymerization changes the equilibrium structure of prelife if
      the rate constants meet certain criteria. In particular, if the basic
      reproductive ratio of sequences of a certain length exceeds one, then those
      sequences can attain high abundance. Furthermore, if many sequences replicate,
      then the longest sequences can reach high abundance even if the basic
      reproductive ratios of all sequences are less than one. We call this phenomenon
      "subcritical life." Subcritical life suggests that sequences long enough to be
      ribozymes can become abundant even if replication is relatively inefficient. Our
      work on the evolution of replication has interesting parallels to infection
      dynamics. Life (replication) can be seen as an infection of prelife.

PMID- 20034502
TI  - Involvement of MAPK proteins in bystander effects induced by chemicals and
      ionizing radiation.
AB  - Many studies have examined bystander effects induced by ionizing radiation,
      however few have evaluated the ability of chemicals to induce similar effects. We
      previously reported the ability of two chemicals, mitomycin C (MMC) and
      phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell
      lines. The focus of the current study was to determine the involvement of the
      MAPK proteins in bystander effects induced by physical and chemical DNA damaging
      agents and to evaluate the effects of MAPK inhibition on bystander-induced
      caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2,
      JNK, and p38, were measured from 1 to 24h following direct or bystander exposure
      to MMC, PHL or radiation. We observed transient phosphorylation, at early time
      points, of all 3 proteins in bystander cells. We also evaluated the effect of
      MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role
      of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced
      activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins
      resulted in a decrease in caspase 3/7 activity at the early time points, and the
      caspase activity increased (in the case of ERK inhibition) or returned to basal
      levels (in the case of JNK or p38 inhibition) between 12 and 24h. PHL is
      considered to be a radiomimetic agent, however in the present study PHL behaved
      more like a chemical and not like radiation in terms of MAPK phosphorylation.
      These results point to the involvement of MAPK proteins in the bystander effect
      induced by radiation and chemicals and provide additional evidence that this
      response is not limited to radiation but is a generalized stress response in
      cells.

PMID- 20034504
TI  - A critical review of fundamental controversies in the field of GPR30 research.
AB  - The female sex hormone estradiol plays an important role in reproduction, mammary
      gland development, bone turnover, metabolism, and cardiovascular function. The
      effects of estradiol are mediated by two classical nuclear receptors, estrogen
      receptor alpha (ERalpha) and estrogen receptor beta (ERbeta). In 2005, G-protein
      coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen
      receptor that was also activated by the ERalpha and ERbeta antagonists tamoxifen
      and fulvestrant (ICI 182780). Despite many conflicting results regarding the
      potential role of GPR30 as an estrogen receptor, the official nomenclature was
      changed to GPER (G-protein-coupled estrogen receptor). This review revisits the
      inconsistencies that still exist in the literature and focuses on selected
      publications that basically address the following two questions: what is the
      evidence for and against the hypothesis that GPR30 acts as an estrogen receptor?
      What is the potential in vivo role of GPR30? Thus, in the first part we focus on
      conflicting results from in vitro studies analysing the subcellular localization
      of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to
      signal) in response to estradiol. In the second part, we discuss the strengths
      and limitations of four available GPR30 mouse models. We elucidate the potential
      impact of different targeting strategies on phenotypic diversity.

PMID- 20034505
TI  - Deacylation reactions of 20-acetyl dinorcholanic lactones and 20,23-diacetyl
      furost-22-enes.
AB  - We report the deacylation of (20R)-20-acetyl-23,24-dinorcholanic lactones by
      hydrazine hydrate, under microwave irradiation in high yields. The elimination of
      the 20-acetyl group proceeded with retention of configuration which contrast with
      other proved deacylation methods that yield a mixture of diastereoisomers. In
      this way, unnatural (20R)-23,24-dinorcholanic lactones can be produced rapidly on
      a large scale. Both (20R)- and (20S)-lactones were prepared starting from
      diosgenin, hecogenin and sarsasapogenin, in 72-80% overall yields.

PMID- 20034503
TI  - Brain substrates of learning and retention in mild cognitive impairment diagnosis
      and progression to Alzheimer's disease.
AB  - Understanding the underlying qualitative features of memory deficits in mild
      cognitive impairment (MCI) can provide critical information for early detection
      of Alzheimer's disease (AD). This study sought to investigate the utility of both
      learning and retention measures in (a) the diagnosis of MCI, (b) predicting
      progression to AD, and (c) examining their underlying brain morphometric
      correlates. A total of 607 participants were assigned to three MCI groups (high
      learning-low retention; low learning-high retention; low learning-low retention)
      and one control group (high learning-high retention) based on scores above or
      below a 1.5 SD cutoff on learning and retention indices of the Rey Auditory
      Verbal Learning Test. Our results demonstrated that MCI individuals with
      predominantly a learning deficit showed a widespread pattern of gray matter loss
      at baseline, whereas individuals with a retention deficit showed more focal gray
      matter loss. Moreover, either learning or retention measures provided good
      predictive value for longitudinal clinical outcome over two years, although
      impaired learning had modestly better predictive power than impaired retention.
      As expected, impairments in both measures provided the best predictive power.
      Thus, the conventional practice of relying solely on the use of delayed recall or
      retention measures in studies of amnestic MCI misses an important subset of older
      adults at risk of developing AD. Overall, our results highlight the importance of
      including learning measures in addition to retention measures when making a
      diagnosis of MCI and for predicting clinical outcome.

PMID- 20034507
TI  - Special issue on safety assessment.

PMID- 20034506
TI  - Acrolein consumption induces systemic dyslipidemia and lipoprotein modification.
AB  - Aldehydes such as acrolein are ubiquitous pollutants present in automobile
      exhaust, cigarette, wood, and coal smoke. Such aldehydes are also constituents of
      several food substances and are present in drinking water, irrigation canals, and
      effluents from manufacturing plants. Oral intake represents the most significant
      source of exposure to acrolein and related aldehydes. To study the effects of
      short-term oral exposure to acrolein on lipoprotein levels and metabolism, adult
      mice were gavage-fed 0.1 to 5 mg acrolein/kg bwt and changes in plasma
      lipoproteins were assessed. Changes in hepatic gene expression related to lipid
      metabolism and cytokines were examined by qRT-PCR analysis. Acrolein feeding did
      not affect body weight, blood urea nitrogen, plasma creatinine, electrolytes,
      cytokines or liver enzymes, but increased plasma cholesterol and triglycerides.
      Similar results were obtained with apoE-null mice. Plasma lipoproteins from
      acrolein-fed mice showed altered electrophoretic mobility on agarose gels.
      Chromatographic analysis revealed elevated VLDL cholesterol, phospholipids, and
      triglycerides levels with little change in LDL or HDL. NMR analysis indicated
      shifts from small to large VLDL and from large to medium-small LDL with no change
      in the size of HDL particles. Increased plasma VLDL was associated with a
      significant decrease in post-heparin plasma hepatic lipase activity and a
      decrease in hepatic expression of hepatic lipase. These observations suggest that
      oral exposure to acrolein could induce or exacerbate systemic dyslipidemia and
      thereby contribute to cardiovascular disease risk.

PMID- 20034508
TI  - Crotoxin is responsible for the long-lasting anti-inflammatory effect of Crotalus
      durissus terrificus snake venom: involvement of formyl peptide receptors.
AB  - In the present study, it was investigated which components are responsible for
      the anti-inflammatory properties of Crotalus durissus terrificus venom (CdtV).
      The effect of crotoxin, as well as of other CdtV components was evaluated on
      edema, cell migration and alterations in leukocyte-endothelium interactions
      induced by carrageenan. Crotoxin (40 microg kg(-1)) was injected at different
      time periods before or after the injection of carrageenan (15 mg kg(-1)) into the
      mouse hind paw, peritoneum or scrotum. Results showed that crotoxin, but not
      other CdtV components, significantly inhibited inflammatory edema and cell
      migration when administered before or after carrageenan injection in mice. This
      toxin also prevented the occurrence of alterations in leukocyte-endothelium
      interactions induced by carrageenan injection, such as the increase in adhered
      cells. In animals pretreated with Boc2 (a selective antagonist of formyl peptide
      receptors), crotoxin showed neither inhibitory effects on edema and cell
      migration, nor prevented alterations in leukocyte-endothelium interactions
      induced by carrageenan. These findings demonstrate that crotoxin is the component
      responsible for the long-lasting anti-inflammatory activity of crude C. durissus
      terrificus venom, and activation of formyl peptide receptors seems to play a
      major role in this effect.

PMID- 20034509
TI  - Conidial surface proteins of Metarhizium anisopliae: Source of activities related
      with toxic effects, host penetration and pathogenesis.
AB  - Conidial contact with an arthropod surface is the first step of the fungal
      penetration and infection process. However, conidia of Metarhizium anisopliae
      have associated components, like enzymes that could be involved in triggering the
      penetration process and toxic effects that have not yet been well characterized.
      Fungi produce many enzymes that also are toxic components found in bacteria and
      animal venoms and thus may be considered as potential virulence factors. In this
      work, we report several enzymatic activities from spore surface protein extracts.
      The major proteolytic activities observed in spore surface proteins (SSP) were
      Pr1 and Pr2 activities, in that order. According to the zymograms obtained, SSP
      contain different proteases. SSP contain trehalase, exo- and endo-chitinase
      activities, and seven different chitinase bands which have been observed in
      zymograms. Activities involved in protection against reactive oxygen species
      (ROS) were also detected. Two lipolytic enzymes were also detected in lipase
      zymograms. Phospholipase C activity, closely related to microbial pathogenesis,
      was detected for the first time in M. anisopliae conidia. These activities
      described could be an initial step towards understanding the mechanisms involved
      in the first stage of M. anisopliae infection process and its toxic effects
      against arthropod hosts.

PMID- 20034511
TI  - Independence in the processing of first- and second-order motion signals at the
      local-motion-pooling level.
AB  - The interaction of first- and second-order motion signals at the local-motion
      pooling level were investigated using locally-paired dots that moved orthogonally
      to each other. Dots were either luminance-defined, which could, potentially drive
      both first- and second-order local-motion units, or contrast-defined, which only
      drive second-order local-motion units. The response measure used was the nature
      of the motion percept: either unidirectional or transparent motion. The
      likelihood of perceiving transparent motion was varied by adjusting the
      trajectory length of the dots. Increasing the trajectory length increased the
      likelihood that observers would perceive transparency. The results, taken as a
      whole, support the notion of independent first-order and second-order local
      motion-pooling units, with the spatial extent of the second-order units being
      larger than that of the first-order units.

PMID- 20034510
TI  - Population coding under normalization.
AB  - A common computation in visual cortex is the divisive normalization of responses
      by a pooled signal of the activity of cells within its neighborhood. From a
      geometrical point of view, normalization constraints the population response to
      high-contrast stimuli to lie on the surface of a high-dimensional sphere. Here we
      study the implications this constraint imposes on the representation of a
      circular variable, such as the orientation of a visual stimulus. New results are
      derived for the infinite dimensional case of a homogeneous populations of neurons
      with identical tuning curves but different orientation preferences. An important
      finding is that the ability of the population to discriminate between any two
      orientations depends exclusively on the Fourier amplitude spectrum of the
      orientation tuning curve. We also study the problem of encoding by a finite set
      of neurons. A central result is that, under normalization, optimal encoding can
      be achieved by a finite number of neurons with heterogeneous tuning curves. In
      other words, increasing the number of neurons in the population does not always
      allow for an improved population code. These results are used to estimate the
      number of neurons involved in the coding of orientation at one position in the
      visual field. If the cortex were to code orientation optimally, we find that a
      small number (~4) of neurons should suffice.

PMID- 20034512
TI  - Orientation specificity of learning vernier discriminations.
AB  - Orientation selective neurons in the primary visual cortex typically respond to a
      range of orientations that covers 20 degrees or more, while in psychophysical
      experiments, orientation bandwidth is often clearly narrower. Here, we measure
      the orientation specificity of perceptual learning for vernier discriminations.
      More than 70 observers, in separate groups, practiced a vernier discrimination
      task with a constant stimulus orientation. After a 1h session of training, the
      vernier was rotated by 2 degrees, 4 degrees, 10 degrees, 20 degrees, 45 degrees
      or 90 degrees. Improvement through training in the first session transferred to
      the second session (tested on the next day) up to 10 degrees of stimulus
      rotation. We found no transfer for rotations of 20 degrees, 45 degrees and 90
      degrees. Hence, the orientation half-bandwidth of perceptual learning is around
      15 degrees, leading to a bandwidth of 30 degrees and corresponding to that of
      single neurons in early visual cortices, while being narrower than that in higher
      cortical areas.

PMID- 20034513
TI  - Differential vertical visual latency as determined with a simultaneity paradigm.
AB  - Behavioral studies, as well as anatomical and physiological data, suggest
      differences in functionality for inferior and superior visual fields. Previous
      investigations comparing latencies of the two fields have employed motor reaction
      times. This approach is of limited usefulness in elderly clinical populations
      where various degrees of motor impairment may be present. In this report, we
      describe a simultaneity paradigm that allows the determination of relative
      latencies without dependence on motor reaction times. A slightly, but
      statistically significant, shorter latency (3.9+/-5.9ms) was found for the
      superior visual field. The results are not affected by age, and both within- and
      between-session variability are low.

PMID- 20034514
TI  - Dyslipidemia in seven Latin American cities: CARMELA study.
AB  - OBJECTIVE: The objective of this study was to describe the prevalence of
      dyslipidemia in the CARMELA study population. METHODS: CARMELA was a cross
      sectional study of cardiovascular risk conducted between September 2003 and
      August 2005 in adults (aged 25 to 64 years) living in Barquisimeto (n=1,824),
      Bogota (n=1,511), Buenos Aires (n=1,412), Lima (n=1,628), Mexico City (n=1,677),
      Quito (n=1,620), and Santiago (n=1,605). Dyslipidemia was defined as the presence
      of one or more of the following conditions: triglycerides>/=200 mg/dL, or total
      cholesterol (TC)>/=240 mg/dL, or HDL cholesterol<40 mg/dL, or LDL cholesterol=not
      optimal, or currently taking antilipemic agents. RESULTS: Prevalence rates of
      dyslipidemia in men and women were: 75.5% (CI: 71.9-79.1) and 48.7% (CI: 45.4
      51.9) in Barquisimeto; 70% (CI: 66.2-73.8) and 47.7% (CI: 43.9-51.5) in Bogota;
      50.4% (CI: 46.8-54.0) and 24.1% (CI: 21.0-27.2) in Buenos Aires; 73.1% (CI: 69.3
      76.8) and 62.8% (CI: 59.2-66.5) in Lima; 62.5% (CI: 58.5-66.5) and 37.5% (CI:
      33.5-41.6) in Mexico City; 52.2% (CI: 47.9-56.5) and 38.1% (CI: 34.5-41.7) in
      Quito; and, 50.8% (CI: 47.1-54.4) and 32.8% (CI: 29.3-36.3) in Santiago.
      CONCLUSIONS: Dyslipidemia was disturbingly prevalent and varied across cities.
      The most frequent dyslipidemia was low HDL-C followed by high triglycerides. The
      high TC/HDL-C ratios and non-HDL-C levels suggest a high risk of cardiovascular
      disease.

PMID- 20034515
TI  - Identification and expression analysis of the g-type and c-type lysozymes in
      grass carp Ctenopharyngodon idellus.
AB  - Lysozyme is an important molecule of innate immune system for the defense against
      bacterial infections. We identified two genes encoding g-type and c-type
      lysozymes from grass carp Ctenopharyngodon idellus by the RACE method. The
      deduced amino acids of both lysozymes possessed typical structural residues and
      conserved catalytic sites similar to their counterparts across the species. In
      contrast, there was only 8.6% similarity of amino acid sequence between these two
      lysozymes. Phylogenetic analyses revealed that these two genes evolved at
      different rate. C-type lysozyme of grass carp was diverged early in the
      evolutionary history. Moreover, the expression patterns of these two genes
      differed. The mRNA levels of both genes were increased after bacterial infection,
      but the up-regulation of g-type lysozyme was much stronger than that of c-type
      lysozyme. We also showed that the c-type and g-type recombinant lysozymes
      possessed different lytic activities against fish bacterial pathogens. These
      results confirmed that both lysozymes play important roles in the defense of
      grass carp against bacterial infections. The g-type lysozyme may be induced for
      the defense against bacterial infections, while c-type lysozyme might be the main
      molecule for the house-keeping defense under normal conditions. These two types
      of lysozymes likely use different mechanisms to regulate their expressions.

PMID- 20034516
TI  - Contribution of hippocampal region CA3 to consciousness and schizophrenic
      hallucinations.
AB  - Recent advances in understanding hippocampal information processing offer new
      vistas on the mind-body and binding problems. Information encoded by the
      autoassociation network of cornu ammonis 3 (CA3) situates landmarks and objects
      within an allocentric framework of space and time. Guiding locomotion across the
      spatial environment, and generally organizing behaviour that transcends space and
      time, the hippocampus creates phenomenal space and time themselves, thus laying
      the foundations for conscious awareness. It is argued that conscious experience
      describes/symbolizes the informational content of self-organizing activity
      patterns in CA3. Imagery, conscious perception or hallucinations do not in
      themselves affect the physical trajectory of behaviour but are evidence for
      patterns of neuronal activity that, acting via the medial prefrontal cortex,
      modulate action dispositions and influence prefrontal top-down attentional
      control of sensory processing and thus subsequent event memory formation.
      Evidence for GABAergic deficit and pyramidal cell hyperexcitability in CA3 in
      patients with schizophrenia is consistent with the notion that binding, by the
      CA3 network, of cortical modules representing weakly related sensory
      representations underlies hallucinations in this disorder.

PMID- 20034517
TI  - Asymmetrical delayed encephalopathy after acute CO intoxication: a case report.
AB  - We report a patient suffering from delayed encephalopathy 21 days after an acute
      CO intoxication. The initial magnetic resonance (MR) images in the acute stage
      show a recent infarct corresponding to a right middle cerebral artery (MCA)
      stenosis. MR images on the 24th day post-intoxication show typical changes of
      delayed encephalopathy. These changes were much more prominent on the areas
      corresponding to right MCA territory while less severe on the other parts. The
      finding suggests an ischemic component contributes to carbon monoxide related
      delayed brain injury.

PMID- 20034518
TI  - Modular double sucrose gap apparatus for improved recording of compound action
      potentials from rat and mouse spinal cord white matter preparations.
AB  - Compound action potential (CAP) recording is a powerful tool for studying the
      conduction properties and pharmacology of axons in multi-axonal preparations. The
      sucrose gap technique improves CAP recording by replacing the extracellular
      solution between the recording electrodes with a non-conductive sucrose solution
      to minimize extracellular shunting. The double sucrose gap (DSG), conferring
      similar advantages at the stimulation site, has been extensively used on guinea
      pig spinal cord white matter (WM) in vitro. Establishing the DSG methodology for
      WM preparations from smaller animals such as rats and mice is appealing due to
      their extensive use in basic and translationally oriented research. Here we
      describe a versatile modular DSG apparatus with rubber membrane separation of the
      compartments, suitable for WM strips from rat and mouse spinal cord. The small
      volumes of compartments (<0.1 ml) and the air-tight design allow perfusion rates
      of 0.5-1 ml/min with faster refreshment rates compared to commonly used 2-3
      ml/min and larger compartments, providing economical usage of expensive
      pharmacological drugs. Our improved DSG design is particularly efficient for
      uncovering slower conducting, higher threshold CAP components, as demonstrated by
      recordings of C-wave (non-myelinated axons) in rat dorsal WM. In myelin-deficient
      Shiverer mice with genetically dysmyelinated axons, our DSG apparatus recordings
      revealed a multi-peak C-wave without preceding faster components. The improved
      stimulation and recording with our DSG apparatus, lowering the range of required
      stimulus intensities and reducing the artifact interference with recorded CAPs
      provide for critical technical advantages that allow for more detailed analysis
      of CAPs in relatively short preparations.

PMID- 20034519
TI  - An instrumented glove for small primates.
AB  - The Cymanus is a novel flex sensor glove for measuring hand kinematics in
      primates. It was used to monitor 9 joints of a rhesus macaque performing a
      grasping task with 25 objects. Over 6 days, the monkey tolerated the glove and
      showed no significant impairment in performance. The sensors linearly tracked
      joint angles, with joint trajectories preserved over days. Angular positions
      discriminated objects as accurately as electromyograms recorded simultaneously
      from 24 arm and hand muscles, and were maximally informative of object identity
      at the end of reach-to-grasp. In a further validation of the glove, muscle
      activity controlling a joint was correlated with the joint's angular acceleration
      70 ms later.

PMID- 20034520
TI  - Comparison of visually evoked local field potentials in isolated turtle brain:
      patterned versus blank stimulation.
AB  - Isolated turtle brain/eye preparation has recently been used as a bloodless
      animal model for detecting the magnetic resonance imaging (MRI) signal changes
      produced by visually evoked neuronal currents. The present work aims to determine
      whether checkerboard-patterned or full field flash (blank) stimulation should be
      used in order to achieve stronger neuronal responses in turtle brain/eye
      preparation. The knowledge gained in this study is essential for optimizing the
      visual stimulation methods in functional neuroimaging studies using turtle
      brain/eye preparation. In this study, visually evoked local field potentials
      (LFPs) were measured and compared in turtle visual cortex and optic tectum
      elicited by checkerboard and full field flash stimuli with three different inter
      stimulus intervals (ISIs=5, 10, and 16s). It was found that the behavior of
      neuronal adaptation in the cortical and tectal LFP signals for checkerboard
      stimulation was comparable to flash stimulation. In addition, there was no
      significant difference in the LFP peak amplitudes (ISI=16s) between these two
      stimuli. These results indicate that the intensity of neuronal responses to
      checkerboard is comparable to flash stimulation. These two stimulation methods
      should be equivalent in functional neuroimaging studies using turtle brain/eye
      preparation.

PMID- 20034521
TI  - Characterization of potential antiviral resistance mutations in hepatitis B virus
      reverse transcriptase sequences in treatment-naive Chinese patients.
AB  - Full-length hepatitis B virus (HBV) reverse transcriptase (RT) sequences were
      amplified and sequenced among 192 nucleos(t)ide analogue (NA)-naive Chinese
      patients with chronic hepatitis B. Deduced amino acids (AAs) at 42 previously
      reported potential NA resistance (NAr) mutation positions in RT region were
      analyzed. Patients were found with either B-genotype (28.65%) or C-genotype
      (71.35%) infections. Rt53, rt91, rt124, rt134, rt221, rt224, rt238 and rt256 were
      identified as B- and C-genotype-dependent polymorphic AA positions. AA
      substitutions at 11 classical NAr mutation positions, i.e. rt80, rt169, rt173,
      rt180, rt181, rt184, rt194, rt202, rt204, rt236 and rt250, were not detected.
      However, potential NAr mutations were found in 30.73% (59/192) isolates, which
      involved 18 positions including rt53, rt207, rt229, rt238 and rt256, etc. The
      concomitant AA changes of HBsAg occurred in 16.67% (32/192) isolates including
      sG145R mutation. One-third of mutation positions were located in functional RT
      domains (e.g. rt207 and rt233), A-B interdomains (overlapping HBsAg 'a'
      determinant and showing most concomitant immune-associated mutations) and non-A-B
      interdomains (e.g. rt191 and rt213), respectively. Genotypes B and C each showed
      several preferred positions to mutate. These results might provide insights into
      understanding the evolution and selection basis of NAr HBV strains under
      antiviral therapy.

PMID- 20034522
TI  - Psychophysiology of language processes in psychopathology: an overview of the
      special issue.

PMID- 20034523
TI  - Global transcriptional profiles in peripheral blood mononuclear cell during
      classical swine fever virus infection.
AB  - Classical swine fever virus (CSFV) is an etiologic agent that causes a highly
      contagious disease in pigs. Laying a foundation to solve problems in its
      pathogenic mechanism, microarray analysis was performed to detect the gene
      transcriptional profiles in peripheral blood mononuclear cells (PBMC) following
      infection with a Chinese highly virulent CSFV strain Shimen. Three susceptible
      pigs were inoculated intramuscularly with a lethal dose (1.0x10(6) TCID(50)) of
      CSFV. Pigs showed classical CSF signs, depletion of lymphocytes and monocytes
      consistent with CSFV infection, and the CSFV genome was also confirmed in the
      PBMC. The PBMC were isolated at 1, 3, 6 and 9 days post-inoculation (dpi). Total
      RNA were extracted and subjected to microarray analysis. Data showed that
      expression of 847 genes wherein 467 genes were known function and the remaining
      380 genes were unknown function, and 541 up- and 306 down-regulation, altered
      after infection. There were 54, 181, 438 and 354 up- and 61, 120, 218 and 145
      down-regulated genes presented on 1, 3, 6 and 9dpi, respectively. These genes
      were involved in immune response (14.5%), apoptosis (3.3%), signal transduction
      (7.6%), transcription (4.4%), metabolism (11%), transport (3.9%), development
      (6.8%) and cell cycle (3.7%). Results demonstrated its usefulness in exploring
      the pathogenic mechanisms of CSFV.

PMID- 20034524
TI  - Pituitary adenylate cyclase-activating polypeptide ameliorates cisplatin-induced
      acute kidney injury.
AB  - Cisplatin nephrotoxicity involves DNA damage, proinflammatory responses and
      apoptosis/necrosis of renal proximal tubular epithelial cells. Pituitary
      adenylate cyclase-activating polypeptide (PACAP) has been shown to protect
      kidneys from ischemic injury and light chain-induced damage by modulating
      inflammation. Confluent monolayer of HK-2 human renal cells were exposed to 50
      microM cisplatin in the presence or absence of either PACAP38 or p53 siRNA. Mice
      injected with cisplatin were also treated with PACAP38 daily for 3 days. The
      damage to HK-2 cells caused by cisplatin involved the activation of p53, caspase
      7, and poly (ADP-ribose) polymerase-1 (PARP-1). PACAP38 prevented the decrease in
      the apurinic/apyrimidinic endonuclease-1 by suppressing p53 activation and
      blocked the cleavage of caspase-7 and PARP-1 in cisplatin-exposed cells. PACAP
      also markedly inhibited cisplatin-induced apoptotic tubule cell death. Exposure
      to cisplatin significantly suppressed the expression of fibronectin and collagens
      I and IV, and altered the integrin repertoire of human renal tubule cells, while
      PACAP partially reversed the reduction of fibronectin, collagen IV, and the
      integrin subunits in cells exposed to cisplatin. Experiments with PACAP receptor
      antagonists and siRNA silencing of p53 showed that the renoprotection with PACAP
      was mediated by the PAC(1) receptor and through both p53-dependent and 
      independent suppression of apoptosis. PACAP was renoprotective in vivo and
      prevented the rise in blood urea nitrogen and creatinine in mice treated with
      cisplatin. These results suggest that p53 plays a pivotal role in decreased
      integrin-mediated extracellular matrix component expression in cisplatin-induced
      tubule cell apoptosis, and reveal a novel aspect of PACAP-mediated
      renoprotection.

PMID- 20034525
TI  - Functional characterization of two human receptor activity-modifying protein 3
      variants.
AB  - Adrenomedullin (AM) and amylin are involved in angiogenesis/lymphangiogenesis and
      glucose homeostasis/food intake, respectively. They activate receptor activity
      modifying protein (RAMP)/G protein-coupled receptor (GPCR) complexes. RAMP3 with
      the calcitonin receptor-like receptor (CLR) forms the AM(2) receptor, whereas
      when paired with the calcitonin receptor AMY(3) receptors are formed. RAMP3
      interacts with other GPCRs although the consequences of these interactions are
      poorly understood. Therefore, variations in the RAMP3 sequence, such as single
      nucleotide polymorphisms or mutations could be relevant to human health. Variants
      of RAMP3 have been identified. In particular, analysis of AK222469 (Homo sapiens
      mRNA for receptor (calcitonin) activity-modifying protein 3 precursor variant)
      revealed several nucleotide differences, three of which encoded amino acid
      changes (Cys40Trp, Phe100Ser, Leu147Pro). Trp56Arg RAMP3 is a polymorphic variant
      of human RAMP3 at a conserved amino acid position. To determine their function we
      used wild-type (WT) human RAMP3 as a template for introducing amino acid
      mutations. Mutant or WT RAMP3 function was determined in Cos-7 cells with CLR or
      the calcitonin receptor (CT((a))). Cys40Trp/Phe100Ser/Leu147Pro RAMP3 was
      functionally compromised, with reduced AM and amylin potency at the respective
      AM(2) and AMY(3(a)) receptor complexes. Cys40Trp and Phe100Ser mutations
      contributed to this phenotype, unlike Leu147Pro. Reduced cell-surface expression
      of mutant receptor complexes probably explains the functional data. In contrast,
      Trp56Arg RAMP3 was WT in phenotype. This study provides insight into the role of
      these residues in RAMP3. The existence of AK222469 in the human population has
      implications for the function of RAMP3/GPCR complexes, particularly AM and amylin
      receptors.

PMID- 20034526
TI  - Intermittent MTII application evokes repeated anorexia and robust fat and weight
      loss.
AB  - Central melanocortins (MC) evoke potent but transient anorectic responses with
      tachyphylaxis developing within days. We hypothesized that intermittent therapy
      using the MC analog, melanotan II (MTII), would minimize the tachyphylaxis and
      enhance the long-term efficacy of MTII treatment. F344/BN rats were infused with
      MTII or vehicle into the lateral ventricle by mini pump for 14 days. Half the
      MTII-infused rats were then given vehicle (MTII-On/Off), while the remaining
      received fresh MTII (MTII-On) for 10 days. Finally, pumps in both groups were
      replaced with ones containing fresh MTII for an additional 6 days. The first MTII
      application induced a 30% food reduction that attenuated within 5 days.
      Reapplication of MTII in MTII-On/Off rats, after the off period, invoked a new
      and equally robust anorectic response while continuation of MTII supplement in
      the MTII-On group did not change food intake from the control level. Body weights
      decreased similarly in both MTII groups at termination (day 30). Hypothalamic MC3
      receptor, AgRP, and POMC expressions were unchanged, but MC4 receptor expression
      was diminished by 25%, and adiposity reduced by 80% in both MTII groups. Acetyl
      CoA carboxylase 1 phosphorylation was elevated in perirenal fat by over 10 fold
      with either MTII treatment. In conclusion, intermittent MTII treatment preserves
      anorectic responses but does not prevent tachyphylaxis, whereas constant MTII
      application blunts further food response after the initial tachyphylaxis. Either
      form of MTII administration results in significant weight and adiposity
      reductions, involving perhaps fatty acid oxidation within specific adipose
      tissues.

PMID- 20034528
TI  - Distribution of killer cell immunoglobulin-like receptor genes and 2DS4 alleles
      in the Chinese Han population.
AB  - Killer cell immunoglobulinlike receptors (KIRs) are a diverse family of receptors
      on natural killer cells. The KIR2DS4-deleted variant differs from the normal
      KIR2DS4 sequence by a 22-bp deletion in exon 5, which causes a frame shift,
      yielding a truncated KIR2DS4 protein with loss of the transmembrane and
      cytoplasmic domains of the full-length KIR2DS4 protein. A sequence-based testing
      and TOPO TA cloning system identifying and distinguishing alleles of the KIR2DS4
      gene was established. The method was applied to 150 Chinese Han individuals: 75
      patients who received T-depleted hematopoietic stem cells transplantation and
      their unrelated donors, establishing frequencies of 2DS4 allele and KIR gene
      within the local population. A majority (139) of the 150 samples (92.7%) were
      positive for KIR2DS4. The ratio of deleted to nondeleted versions of KIR2DS4 was
      approximately 1:2. Three KIR2DS4 novel alleles were identified. Forty-four
      percent individuals carried two group A haplotypes. The 17 KIR gene loci were
      found in 21.3%-100% in the population. Our findings suggest that the Chinese Han
      population is distinct in KIR gene frequencies and 2DS4 allele frequencies in
      comparison with some other populations.

PMID- 20034527
TI  - Isolation and characterization of human interleukin-10-secreting T cells from
      peripheral blood.
AB  - Recent studies have expanded our understanding of the role of the anti
      inflammatory cytokine interleukin (IL)-10, produced by multiple lineages of both
      human and murine T cells, in regulating the immune response. Here, we demonstrate
      that the small percentage of circulating CD4(+) T cells that secrete IL-10 can be
      isolated from human peripheral blood and, importantly, we have optimized a
      protocol to expand these cells in both antigen-specific and polyclonal manners.
      Expanded CD4(+)IL-10(+) T cells abrogate proliferation and T helper (Th) 1-like
      cytokine production in an antigen-specific manner, and to a lesser extent exhibit
      bystander suppressive capacity. CD4(+)IL-10(+) T cells are suppressive in a cell
      contact-dependent way, though they do not require secretion of IL-10 for their
      suppressive role in vitro. CD4(+)IL-10(+) T cells have an activated phenotype,
      with high expression of CD25, CD69, and cytotoxic T-lymphocyte antigen-4, and are
      largely FoxP3 negative. This novel method for the isolation and expansion of
      suppressive IL-10-secreting T cells has important implications both for further
      research and clinical therapeutic development.

PMID- 20034529
TI  - Inflammation modifies the pattern and the function of Toll-like receptors
      expressed by human mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSC) are involved in tissue repair and in the
      regulation of immune responses. MSC express Toll-like receptors (TLR) known to
      link innate and adaptive immunity. We hypothesized that TLR signaling could
      influence human MSC (hMSC) function. Here, we show that hMSC express TLR1, TLR2,
      TLR3, TLR4, TLR5, and TLR6 but not TLR7, TLR8, TLR9, and TLR10. In inflammatory
      conditions mimicked by culturing hMSC in an inflammatory environment, TLR2, TLR3,
      and TLR4 are upregulated, whereas TLR6 is downregulated. Interleukin (IL)-1 beta,
      IL-6, IL-12p35 and transforming growth factor-beta mRNAs are constitutively
      expressed by hMSC. Inflammation leads to an increase in IL-1 beta, IL-6, IL
      12p35, and transforming growth factor-beta transcription and is characterized by
      IL-23p19 and IL-27p28 transcription. In this setting, poly(I:C) further augments
      IL-6, IL-12p35, IL-23p19, and IL-27p28 transcription, whereas lipopolysaccharide
      (LPS) increases IL-23p19 and IL-27p28 transcription. By upregulating TLR3 and
      TLR4 transcription, inflammation increases the hMSC responsiveness to LPS and
      poly(I:C), leading to a proinflammatory shift in their cytokine profile. The hMSC
      osteogenic potential does not change after TLR triggering but stimulation with
      LPS and poly(I:C) results in a decrease in their immunosuppressive capabilities.
      In conclusion, TLR activation in hMSC may affect their function and could modify
      their in vivo fate, especially in an inflammatory context.

PMID- 20034530
TI  - Piperine, the main alkaloid of Thai black pepper, protects against
      neurodegeneration and cognitive impairment in animal model of cognitive deficit
      like condition of Alzheimer's disease.
AB  - Recently, numerous medicinal plants possessing profound central nervous system
      effects and antioxidant activity have received much attention as food supplement
      to improve cognitive function against cognitive deficit condition including in
      Alzheimer's disease condition. Based on this information, the effect of piperine,
      a main active alkaloid in fruit of Piper nigrum, on memory performance and
      neurodegeneration in animal model of Alzheimer's disease have been investigated.
      Adult male Wistar rats (180-220 g) were orally given piperine at various doses
      ranging from 5, 10 and 20mg/kg BW at a period of 2 weeks before and 1 week after
      the intracerebroventricular administration of ethylcholine aziridinium ion
      (AF64A) bilaterally. The results showed that piperine at all dosage range used in
      this study significantly improved memory impairment and neurodegeneration in
      hippocampus. The possible underlying mechanisms might be partly associated with
      the decrease lipid peroxidation and acetylcholinesterase enzyme. Moreover,
      piperine also demonstrated the neurotrophic effect in hippocampus. However,
      further researches about the precise underlying mechanism are still required.

PMID- 20034531
TI  - Preconditioning with subneurotoxic allyl nitrile: protection against allyl
      nitrile neurotoxicity.
AB  - High-dose cruciferous allyl nitrile can induce behavioral abnormalities in
      rodents, while repeated exposure to allyl nitrile at subneurotoxic levels can
      increase phase 2 detoxification enzymes in many tissues, although the brain has
      not been investigated yet. In the present study, we examined the effect of 5 days
      repeated exposure to subneurotoxic allyl nitrile (0-400 micromol/kg/day) on the
      brain. Elevated glutathione S-transferase activity was recorded in the striatum,
      hippocampus, medulla oblongata plus pons, and cortex. Enhancement of quinone
      reductase activity was observed in the medulla oblongata plus pons, hippocampus,
      and cortex. In the medulla oblongata plus pons, elevated glutathione levels were
      recorded. Following repeated subneurotoxic allyl nitrile exposure (0-400
      micromol/kg/day), mice were administered a high-dose allyl nitrile (1.2 mmol/kg)
      which alone led to appearance of behavioral abnormalities. Compared with the 0
      micromol/kg/day group, animals in the 200 and 400 micromol/kg/day pre-treatment
      groups exhibited decreased behavioral abnormalities and elevated GABA-positive
      cell counts in the substantia nigra pars reticulata and the interpeduncular
      nucleus. These data suggest that repeated exposure to subneurotoxic levels of
      allyl nitrile can induce phase 2 enzymes in the brain, which together with
      induction in other tissues, may contribute to protection against allyl nitrile
      neurotoxicity.

PMID- 20034533
TI  - Threshold dose for peanut: Risk characterization based upon diagnostic oral
      challenge of a series of 286 peanut-allergic individuals.
AB  - Clinical records of 286 consecutive patients reacting positively with objective
      symptoms to double-blind, placebo-controlled oral peanut challenges at University
      Hospital, Nancy, France were examined for individual No Observed Adverse Effect
      Levels (NOAELs) and Lowest Observed Adverse Effect Levels (LOAELs). After fitting
      to a log-normal probability distribution model, the ED(10) and ED(05) were 14.4
      and 7.3mg (expressed as whole peanut), respectively, with 95% lower confidence
      intervals of 10.7 and 5.2mg, respectively. Compared to results from a previous
      study where the ED(10) was based upon individual peanut thresholds gleaned from
      12 publications, a statistically significant difference was observed between the
      ED(50)'s, but not the ED(10)'s of the two probability distribution curves. The
      Nancy patient group contains more sensitive subjects than the group from the
      published literature thus contributing to the observed differences. Minimum
      eliciting dose-distributions for patients with histories of more severe reactions
      (grade 4 or 5; 40 subjects) did not differ significantly from those of patients
      with histories of less severe reactions (grades 1-3; 123 subjects). These data
      and this modeling approach could be used to establish population thresholds for
      peanut-allergic consumers and thereby provide a sound basis for allergen control
      measures in the food industry.

PMID- 20034532
TI  - Alcohol influence on acrylamide to glycidamide metabolism assessed with
      hemoglobin-adducts and questionnaire data.
AB  - Our purpose was to investigate whether alcohol (ethanol) consumption could have
      an influence on the metabolism of acrylamide to glycidamide in humans exposed to
      acrylamide through food. We studied a subsample from a population-based case
      control study of prostate cancer in Sweden (CAPS). Questionnaire data for alcohol
      intake estimates was compared to the ratio of hemoglobin-adduct levels for
      acrylamide and glycidamide, used as a measure of individual differences in
      metabolism. Data from 161 non-smoking men were processed with regard to the
      influence of alcohol on the metabolism of acrylamide to glycidamide. A negative,
      linear trend of glycidamide-adduct to acrylamide-adduct-level ratios with
      increasing alcohol intake was observed and the strongest association (p-value for
      trend=0.02) was obtained in the group of men with the lowest adduct levels (47
      pmol/g globin) when alcohol intake was stratified by acrylamide-adduct levels.
      The observed trend is likely due to a competitive effect between ethanol and
      acrylamide as both are substrates for cytochrome P450 2E1. Our results, strongly
      indicating that ethanol influence metabolism of acrylamide to glycidamide, partly
      explain earlier observations of only low to moderate associations between
      questionnaire data on dietary acrylamide intake and hemoglobin-adduct levels.

PMID- 20034534
TI  - Scientific evaluation of the chronic toxicity of the herbal medicine CGX in
      beagle dogs.
AB  - CGX is a potential hepatoprotective herbal medicine used to treat various chronic
      liver disorders. The purpose of the study was to evaluate the pharmaceutical
      safety of CGX via a systemic 13-week repeated dose toxicity test in beagle dogs.
      Male and female beagle dogs were divided into four groups and two animals each
      from the control and high-dose group (400 mg/kg) were allocated into recovery
      groups. The dogs were administered with CGX (0, 100, 200, 400 mg/kg) for 13
      weeks. During the experimental period, the dogs were observed for signs of gross
      toxicity and for behavioral changes; body weight and food consumption were
      measured. An ophthalmologic examination and urinalysis were performed at 0 and
      13th week and blood biochemistry and hematological parameters analyses were
      performed at 0, 6th, and 13th week. A histopathological examination was also
      performed at the end of the experiment. There were no CGX-induced abnormalities
      in clinical signs, organ weights, food consumption, hematological, urine, and
      blood biochemical parameters, or histopathological findings in any of the groups
      during or after the 13 weeks. We demonstrated the safety of CGX for 13-week
      repeated dose and considered that it is safe for chronic clinical use.

PMID- 20034535
TI  - Silymarin, the antioxidant component and Silybum marianum extracts prevent liver
      damage.
AB  - Liver disorders are one of the common recent problems affects on the human
      health. These disorders due to many environmental polluted sources. Many herbal,
      medicinal and pharmaceutical plants and their extracts are widely studied by many
      researchers. Silybum marianum got a bright reputation in relieve the liver
      diseases, and that might be for the potent silymarin mixture. Mechanism of action
      for silymarin conducted mainly to the antiradical and anticarcinogenic roles.
      Ethyl acetate (100mg/kg bw) and ethanol seed extracts for S. marianum (100mg/kg
      bw) were tested against the injection (i.p.) by carbon tetrachloride (2 ml/kg bw)
      the inducer of liver damage. Their activity were compared with standard hepatic
      drug hepaticum (100mg/kg bw) for 10 days. Ethanolic extract showed the most
      significantly decrease in the liver enzymes. For the oxidative experiments, ethyl
      acetate showed the most increase for glutathione level and the risk factor
      HDL/LDL significantly. Hepaticum was the most powerful group for the significant
      decreasing for malondialdehyde and fucosidase activity. Some equal improvements
      were noticed in the histopathological studies for the protective groups.

PMID- 20034536
TI  - Levels of mint and wintergreen flavorants: smokeless tobacco products vs.
      confectionery products.
AB  - Nicotine and flavorant compound levels were measured in 10 "mint"-related sub
      brands and 8 "wintergreen" sub-brands of smokeless tobacco (SLT). Also analyzed
      were "mint"-related and "wintergreen" confectionery products. Of the "mint" SLT,
      "Timberwolf Packs Mint Pouches" contained the highest menthol level (5.3 mg/g);
      the average for the five most-highly mentholated SLT products was 4.3 mg/g. The
      average for the most five most-highly mentholated confectionery products was 3.5
      mg/g. For hard candy, a reported average of maximum use levels is 2.1 mg/g
      (Burdock, 2009). Of the "wintergreen" SLT, "Hawken Wintergreen" was found to
      contain the highest methyl salicylate (MS) level (29.7 mg/g). The average of the
      five highest SLT MS levels was 23.8 mg/g, i.e., 5x higher than the level found in
      the confectionery product with the highest MS level (LifeSavers Wint O Green
      Sugar Free, 4.6 mg/g). For hard candy, a reported average of maximum use levels
      is 2.0 mg/g (Burdock, 2009). Assuming 23.8 mg/g MS in SLT, SLT use at 15 g/day,
      100% bodily absorption of the MS, and 60 kg body weight, the average daily intake
      would be 6.0 mg/kg-day, i.e., 12x the acceptable daily intake (ADI) of 0.5 mg/kg
      day established for this compound by a joint FAO/WHO committee.

PMID- 20034537
TI  - Apoptosis induction of human leukemia U937 cells by gomisin N, a
      dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill.
AB  - We compared the pro-apoptotic effect of two dibenzocyclooctadiene lignans,
      gomisin A and gomisin N, isolated from Schizandra chinensis Baill, in U937 human
      promyelocytic leukemia cells in vitro. Gomisin N, but not gomisin A, inhibited
      cell growth in a dose-dependent manner, which was associated with the induction
      of apoptosis. The increase in apoptosis that was induced by gomisin N was
      correlated with down-regulation of anti-apoptotic Bcl-2 expression, a decrease in
      the mitochondrial membrane potential (MMP) and a release of cytochrome c from the
      mitochondria into the cytosol. Furthermore, gomisin N induced the proteolytic
      activation of caspase-9 and -3 and a concomitant degradation of poly(ADP-ribose)
      polymerase. However, caspase-8 was not activated and cleavage of Bid was not
      observed in gomisin N-treated U937 cells. The cytotoxic effects and apoptotic
      characteristics induced by gomisin N were significantly inhibited by z-DEVD-fmk,
      a caspase-3 inhibitor, demonstrating the important role that caspase-3 plays in
      the process. We conclude that gomisin N induces the apoptosis of U937 cells
      through a signaling cascade of mitochondria-mediated intrinsic caspase pathways
      and gomisin N may be a useful chemotherapeutic agent.

PMID- 20034538
TI  - Ether oxygenate additives in gasoline reduce toxicity of exhausts.
AB  - Fuel additives can improve combustion and knock resistance of gasoline engines.
      Common additives in commercial fuels are "short-chain, oxygen containing
      hydrocarbons" such as methyl tert-butyl ether (MTBE) and ethyl tert-butyl ether
      (ETBE). Since these additives change the combustion characteristics, this may as
      well influence toxic effects of the resulting emissions. Therefore we compared
      toxicity and BTEX emissions of gasoline engine exhaust regarding addition of MTBE
      or ETBE. Non-reformulated gasoline served as basic fuel. This fuel was
      supplemented with 10%, 20%, 25% and 30% ETBE or 15% MTBE. The fuels were
      combusted in a gasoline engine at idling, part load and rated power. Condensates
      and particulate matter (PM) were collected and PM samples extracted with
      dichloromethane. Cytotoxic effects were investigated in murine fibroblasts (L929)
      using the neutral red uptake assay and mutagenicity using the bacterial reverse
      mutation assay. BTEX emissions were analyzed by gas chromatography. RESULTS: PM
      extracts showed mutagenicity with and without metabolic activation. Mutagenicity
      was reduced by the addition of MTBE and ETBE, 10% ETBE being most effective. The
      condensates produced no significant mutagenic response. The cytotoxicity of the
      condensates from ETBE- and MTBE-reformulated fuels was reduced as well. The BTEX
      content in the exhaust was lowered by the addition of MTBE and ETBE. This effect
      was significantly related to the ETBE content at rated power and part load.
      CONCLUSIONS: Addition of MTBE and ETBE to fuels can improve combustion and leads
      to decreased toxicity and BTEX content of the exhaust. Reduction of mutagenicity
      in the PM-extracts is most probably caused by a lower content of polycyclic
      aromatic hydrocarbons.

PMID- 20034539
TI  - Profiling gene expression of whole cytochrome P450 superfamily in human bronchial
      and peripheral lung tissues: Differential expression in non-small cell lung
      cancers.
AB  - Susceptibility to lung diseases, such as lung cancer and chronic obstructive
      pulmonary disease, is largely influenced by the metabolic capacity of lung
      tissues. This capacity is partly determined by the expression profile of the
      cytochromes P450 (CYPs), a superfamily of enzymes that have relevant catalytic
      properties toward exogenous and endogenous compounds. Using quantitative real
      time RT-PCR, we conducted a comprehensive analysis of the expression profile of
      the 57 human CYP genes in non-tumoral (bronchial mucosa and pulmonary parenchyma)
      and tumoral lung tissues of 18 patients with non-small cell lung cancer. This
      study highlights (i) inter-individual variations in lung expression for some
      CYPs, (ii) different CYP expression patterns between bronchial mucosa and
      pulmonary parenchyma, that indicate distinctive susceptibility of these tissues
      toward the deleterious effects of inhaled chemical toxicants and carcinogens,
      (iii) high intertumoral variability, that could have major implications on lung
      tumor response to anti-cancer drugs.

PMID- 20034540
TI  - Primate FSH-receptor promoter nucleotide sequence heterogeneity affects FSH
      receptor transcription.
AB  - Follicle-stimulating hormone (FSH) is essential for primate reproduction and acts
      via the FSH-receptor (FSHR). Although the FSHR expression is highly cell
      specific, knowledge of the FSHR promoter and its transcriptional regulation is
      very limited. We applied a comparative genomic approach of important primate
      lineages to characterize the FSHR core promoter region. The core promoter
      sequences of the human and different primate species display significant
      variations in species-specific promoter activities shown by relative luciferase
      activity (RLA), ranging from 0.7-fold in the bonobo up to 3.5-fold in the
      chimpanzee compared to human. Comparison of the core promoter sequences revealed
      only very few interspecies nucleotide mismatches. Sequence homology ranged
      between 88% in the marmoset to 98% in chimpanzee compared to human FSHR.
      Mutagenesis of a single nucleotide next to a putative E-twenty-six (ETS) binding
      site caused a significant increase for human and a decrease for chimpanzee in
      RLA. An accompanying change in the pattern of protein binding to mutated human
      and chimpanzee ETS binding sites was demonstrated by EMSA, confirming a hitherto
      unknown role for this ETS binding site in FSHR promoter activity. Although the
      FSHR promoter displays a great sequence homology among primates, single
      nucleotide changes have significant impact on FSHR promoter activity. Thus
      promoter studies of closely related species could yield important insights into
      different regulatory promoter elements caused by nucleotide substitutions.

PMID- 20034541
TI  - Cyclooxygenase-1 mediates the immediate corticosterone response to peripheral
      immune challenge induced by lipopolysaccharide.
AB  - Immune-induced activation of the hypothalamus-pituitary-adrenal axis is mediated
      by cyclooxygenase derived prostaglandins. Here we examined the role of
      cyclooxygenase-1 in this response, by using genetically modified mice as well as
      pharmacological inhibition. We found that mice with a deletion of the gene
      encoding cyclooxygenase-1, in contrast to wild type mice, did not show increased
      plasma corticosterone at 1h after immune challenge by peripheral injection of
      bacterial wall lipopolysaccharide, whereas the corticosterone levels were
      similarly elevated in both genotypes at 6h post-injection. Pretreatment of mice
      with the selective cyclooxygenase-1 inhibitor SC-560, given orally, likewise
      inhibited the rapid corticosterone response. These findings, taken together with
      our recent demonstration that the delayed stress hormone response to immune
      challenge is dependent on cyclooxygenase-2, show that the two cyclooxygenase
      isoforms play distinct, but temporally supplementary roles for the stress hormone
      response to inflammation.

PMID- 20034542
TI  - Paradoxical association of the brain-derived-neurotrophic-factor val66met
      genotype with response inhibition.
AB  - Response inhibition is a basic executive function which is dysfunctional in
      various basal ganglia diseases. The brain-derived-neurotrophic-factor (BDNF)
      plays an important pathophysiological role in these diseases. In the current
      study we examined the functional relevance of the BDNF val66met polymorphism for
      response inhibition processes in 57 healthy human subjects using event-related
      potentials (ERPs), i.e. the Nogo-N2 and Nogo-P3, which likely reflect different
      aspects of inhibition. Our results support the pre-motor inhibition theory of the
      Nogo-N2. We show that the BDNF val66met polymorphism selectively modulates the
      Nogo-N2. Response inhibition was better in the val/met-met/met group, since this
      group committed fewer false alarms, and their Nogo-N2 was larger, compared to the
      val/val group. This is the first study showing that met alleles of the BDNF
      val66met polymorphism confer an advantage for a specific cognitive function. We
      propose a neuronal model how this advantage gets manifest on a neuronal level.

PMID- 20034543
TI  - Insulin-like growth factor-1 stimulation of hypothalamic KiSS-1 gene expression
      is mediated by Akt: effect of alcohol.
AB  - Kisspeptin, as well as insulin-like growth factor-1 (IGF-1), act centrally to
      stimulate luteinizing hormone-releasing hormone (LHRH) secretion at puberty. IGF
      1 can induce KiSS-1 gene expression as an early pubertal event; however, the
      signaling pathway mediating this effect is not known. Since alcohol (ALC) blocks
      IGF-1 induced LHRH release acutely, we assessed whether this drug could affect
      IGF-1 stimulated prepubertal KiSS-1 gene expression following a binge type of
      exposure. Immature female rats were administered either ALC (3 g/kg) or water via
      gastric gavage at 07.30 h. At 09.00 h the ALC and control groups were subdivided
      where half received either saline or IGF-1 (200 ng) into the third ventricle. A
      second dose of ALC (1.5, 2 and 3 g/kg) or water was administered at 11.30 h.
      These regimens produced moderate blood alcohol concentrations of 77, 89 and 117
      mg/dl, respectively, over the time course of the experiment. Rats were sacrificed
      6 h after the IGF-1 injection and tissues containing the anteroventral
      periventricular (AVPV) and arcuate (ARC) nuclei were collected. IGF-1 stimulated
      (P<0.01) KiSS-1 gene expression in the AVPV nucleus at 6 h, but did not affect
      expression of the kisspeptin receptor, GPR54. While ALC did not alter basal
      expression of either gene, its dose dependently blocked IGF-1-induced KiSS-1 gene
      expression in the AVPV nucleus. No changes were observed in the ARC nucleus.
      Assessment of IGF-1 signaling indicated that the acute administration of IGF-1,
      ALC, or both did not alter the basal expression of IGF-1 receptor protein.
      However, IGF-1 stimulated (P<0.05) phosphorylated Akt protein over basal levels,
      an action blocked by ALC. Our results indicate that the IGF-1 induction of KiSS-1
      gene expression is mediated by Akt activation, and that ALC alters this important
      prepubertal action of IGF-1.

PMID- 20034544
TI  - Anatomical changes in the primary visual cortex of the congenitally blind Crx-/-
      mouse.
AB  - Mutations in the human cone-rod homeobox (Crx) gene are associated with retinal
      dystrophies such as Leber Congenital Amaurosis (LCA), characterized by complete
      or near complete absence of vision from birth. The photoreceptors of Crx-/- mice
      lack outer segments, and therefore cannot capture light signals through rods and
      cones, thus resulting in a lack of normal retinal ganglion cell activity from
      birth. Using specific antibodies to subsets of neurons and markers of activity,
      we examined the impact of this absence of sensory input on the development of the
      primary visual cortex (V1) in early postnatal Crx-/- mice, before wiring of the
      visual system is complete, and in adulthood. We revealed that Crx-/- mice did not
      exhibit gross anatomical differences in V1; however, they exhibited significantly
      fewer calcium-binding protein (parvalbumin and calbindin-D28k) expressing
      interneurons, as well as reduced nonphosphorylated neurofilament expression in
      V1. These results reveal that the Crx mutation and lack of light stimulation
      through the photoreceptor pathway regulate the development and phenotype of
      different neuronal populations in V1 but not its general morphology. We conclude,
      therefore, that photoreceptor-mediated visual input during development is crucial
      for the normal postnatal development and maturation of subsets of cortical
      neurons.

PMID- 20034545
TI  - The neurochemistry and innervation patterns of extrinsic sensory and sympathetic
      nerves in the myenteric plexus of the C57Bl6 mouse jejunum.
AB  - In vitro anterograde tracing of axons in mesenteric nerve trunks using
      biotinamide in combination with immunohistochemical labelling was used to
      characterize the extrinsic nerve projections in the myenteric plexus of the mouse
      jejunum. Anterogradely-labelled spinal sensory fibres innervating the enteric
      nervous system were identified by their immunoreactivity for calcitonin gene
      related peptide (CGRP), while sympathetic noradrenergic fibres were detected with
      tyrosine hydroxylase (TH), using confocal microscopy. The presence of these
      markers has been previously described in the spinal sensory and sympathetic
      fibres. Labelled extrinsic nerve fibres in the myenteric plexus were identified
      apposing enteric neurons that were immunoreactive for either calretinin (CalR),
      calbindin (CalB) or nitric oxide synthase (NOS). Of the total anterogradely
      labelled axons in the myenteric plexus, 20% were CGRP-immunoreactive. Labelled
      CGRP-immunoreactive varicosities were closely apposed to CalR-immunoreactive
      myenteric cells, many of which were Dogiel type I (40%; interneurons) or type II
      (20%; intrinsic sensory) neurons. Labelled CGRP-immunoreactive varicosities were
      also observed in close appositions to CalB-immunoreactive myenteric cell bodies,
      of which a small subset had type II morphology (18%; intrinsic sensory neurons).
      A further 43% of all biotinamide-filled fibres were immunoreactive for TH and
      these fibres were apposed to CalR-immunoreactive cell bodies (small-sized;
      excitatory motor neurons) and NOS-immunoreactive cell bodies (either type I or
      small neurons; inhibitory motor neurons and interneurons) in the myenteric
      plexus. The results provide a neurochemical and neuroanatomical basis for
      connections between dorsal root afferent neurons and myenteric neurons and
      suggest an anatomical substrate for the well-known modulation of enteric circuits
      from sympathetic nerves. No anterogradely-labelled fibres were stained for NOS
      immunoreactivity, despite more than 60% of dorsal root ganglion (DRG) neurons
      retrogradely labelled from the jejunum showing NOS-immunoreactivity. This was due
      to a substantial, time-dependent, and apparently selective, loss of NOS from
      extrinsic axons under in vitro conditions. Lastly, a small population of non
      immunoreactive biotinamide-filled fibres (<1%) gave rise to dense terminal
      structures around individual myenteric cell bodies lacking CalR, CalB or NOS.
      These specialized endings may represent vagal fibres or a subset of spinal
      sensory neurons that do not contain CGRP.

PMID- 20034547
TI  - The role of the dorsolateral prefrontal cortex in retrieval from long-term memory
      depends on strategies: a repetitive transcranial magnetic stimulation study.
AB  - The ability to associate a name to a face is a crucially relevant task in daily
      life. In this study, we investigated the neuronal basis of face-name retrieval in
      young subjects using repetitive transcranial magnetic stimulation (rTMS) over the
      left or right dorsolateral prefrontal cortex (DLPFC). The experimental task was
      composed of two study phases: an encoding phase and a retrieval phase. During the
      encoding phase, subjects saw a face (familiar or unfamiliar) followed by a name.
      During the retrieval phase, they saw the face together with two names and had to
      choose the name that was correctly associated with the face. rTMS was delivered
      only during retrieval. In addition, we evaluated the use of memory strategies
      during the task. Accordingly, subjects were subdivided into two groups: strategy
      users (SU) and no-strategy users (NSU). No rTMS effects were present for familiar
      face-name pairs, probably due to a ceiling effect. However, for unfamiliar face
      name pairs, the different use of memory strategies resulted in different rTMS
      effects. The SU group showed a selective interference effect after right DLPFC
      stimulation, whereas the NSU group showed an effect after left DLPFC stimulation.
      Importantly, the overall performance of the two groups was comparable. We suggest
      that during memory retrieval the left DLPFC might be recruited when the subject
      does not apply deliberately a retrieval strategy whereas there is a shift to the
      right DLPFC if cognitive control processes that are engaged by strategies are
      needed to guide episodic retrieval.

PMID- 20034546
TI  - Dynamic changes in cerebello-thalamo-cortical motor circuitry during progression
      of Parkinson's disease.
AB  - Both the basal ganglia and cerebellum are known to influence cortical motor and
      motor-associated areas via the thalamus. Whereas striato-thalamo-cortical (STC)
      motor circuit dysfunction has been implicated clearly in Parkinson's disease
      (PD), the role of the cerebello-thalamo-cortical (CTC) motor circuit has not been
      well defined. Functional magnetic resonance imaging (fMRI) is a convenient tool
      for studying the role of the CTC in vivo in PD patients, but large inter
      individual differences in fMRI activation patterns require very large numbers of
      subjects in order to interpret data from cross-sectional, case control studies.
      To understand the role of the CTC during PD progression, we obtained longitudinal
      fMRI 2 years apart from 5 PD (57+/-8 yr) and five Controls (57+/-9 yr) performing
      either externally- (EG) or internally-guided (IG) sequential finger movements.
      All PD subjects had unilateral motor symptoms at baseline, but developed
      bilateral symptoms at follow-up. Within-group analyses were performed by
      comparing fMRI activation patterns between baseline and follow-up scans. Between
      group comparisons were made by contrasting fMRI activation patterns generated by
      the more-affected and less-affected hands of PD subjects with the mean of the
      dominant and non-dominant hands of Controls. Compared to baseline, Controls
      showed changes in CTC circuits, but PD subjects had increased recruitment of both
      cortical motor-associated and cerebellar areas. Compared to Controls, PD subjects
      demonstrated augmented recruitment of CTC circuits over time that was
      statistically significant when the IG task was performed by the hand that
      transitioned from non-symptomatic to symptomatic. This longitudinal fMRI study
      demonstrates increased recruitment of the CTC motor circuit concomitant with PD
      progression, suggesting a role of the CTC circuit in accommodation to, or
      pathophysiology of, PD.

PMID- 20034548
TI  - Nicotinic receptors in the habenula: importance for memory.
AB  - The habenula is an epithalamic structure through which descending connections
      pass from the telencephalon to the brainstem, putting it in a key location to
      provide feedback control over the brainstem monoaminergic projections ascending
      to the telencephalon. Habenular nuclei lesions have been shown to impair memory
      function. The habenular nuclei have high concentrations of nicotinic receptors.
      In this study we assessed the role of habenular nicotinic receptors for working
      memory. Adult female Sprague-Dawley rats were trained on a 16-arm maze to assess
      spatial working and reference memory. All rats had at least 18 sessions of
      training and then had bilateral chronic infusion cannulae placed into the lateral
      habenula nucleus. These cannulae were each connected to a slow delivery osmotic
      minipump that chronically infused mecamylamine 100 microg/side/day (n=9) or
      vehicle (aCSF) for controls (n=15) for a period of 4 weeks. Both mecamylamine
      infused and control rats were acutely injected (s.c.) with nicotine (0, 0.2 or
      0.4 mg/kg) in a repeated measures counterbalanced design twice at each dose
      during the chronic local infusion period. There was a significant (P<0.025)
      mecamylaminexnicotine interaction effect on memory performance. Without nicotine
      injection the chronic habenular mecamylamine infusion caused a significant
      (P<0.05) increase in total memory errors. The 0.4 mg/kg nicotine dose
      significantly (P<0.005) reversed the mecamylamine-induced memory impairment,
      returning performance back to levels seen in rats with control aCSF habenular
      infusions. The current study determined that nicotinic receptors in the lateral
      habenular nucleus are important for spatial memory function. Descending
      projections from the telencephalon through the habenula to brainstem nuclei using
      nicotinic receptors appear to be a key pathway for memory processing.

PMID- 20034550
TI  - Rethinking sound detection by fishes.
AB  - In this paper we reconsider the designation of fishes as being either "hearing
      specialists" or "hearing generalists," and recommend dropping the terms. We argue
      that this classification is only vaguely and variously defined in the literature,
      and that these terms often have unclear and different meaning to different
      investigators. Furthermore, we make the argument that the ancestral, and most
      common, mode of hearing in fishes involves sensitivity to acoustic particle
      motion via direct inertial stimulation of the otolith organ(s). Moreover, any
      possible pressure sensitivity is the result of the presence of an air bubble
      (e.g., the swim bladder), and that hearing sensitivity may be enhanced by the
      fish having a specific connection between the inner ear to a bubble of air. There
      are data showing that some fish species have a sensitivity to both pressure and
      motion that is frequency dependent. Thus such species could not possibly be
      termed as either hearing "generalists" or specialists," and many more species
      probably could be classified in this way as well. Furthermore, we propose that
      the term "specialization" be reserved for cases in which a species has some kind
      of morphological connection or close continuity between the inner ear and an air
      bubble that affects behavioral sensitivity to sound pressure (i.e., an otophysic
      connection).

PMID- 20034549
TI  - Motion of the surface of the human tympanic membrane measured with stroboscopic
      holography.
AB  - Sound-induced motion of the surface of the human tympanic membrane (TM) was
      studied by stroboscopic holographic interferometery, which measures the amplitude
      and phase of the displacement at each of about 40,000 points on the surface of
      the TM. Measurements were made with tonal stimuli of 0.5, 1, 4 and 8 kHz. The
      magnitude and phase of the sinusoidal displacement of the TM at each driven
      frequency were derived from the fundamental Fourier component of the raw
      displacement data computed from stroboscopic holograms of the TM recorded at
      eight stimulus phases. The correlation between the Fourier estimates and measured
      motion data was generally above 0.9 over the entire TM surface. We used three
      data presentations: (i) plots of the phasic displacements along a single chord
      across the surface of the TM, (ii) phasic surface maps of the displacement of the
      entire TM surface, and (iii) plots of the Fourier derived amplitude and phase
      angle of the surface displacement along four diameter lines that define and
      bisect each of the four quadrants of the TM. These displays led to some common
      conclusions: at 0.5 and 1kHz, the entire TM moved roughly in-phase with some
      small phase delay apparent between local areas of maximal displacement in the
      posterior half of the TM. At 4 and 8 kHz, the motion of the TM became more
      complicated with multiple local displacement maxima arranged in rings around the
      manubrium. The displacements at most of these maxima were roughly in-phase, while
      some moved out-of-phase. Superposed on this in- and out-of-phase behavior were
      significant cyclic variations in-phase with location of less than 0.2 cycles or
      occasionally rapid half-cycle step-like changes in-phase. The high frequency
      displacement amplitude and phase maps discovered in this study can not be
      explained by any single wave motion, but are consistent with a combination of low
      and higher order modal motions plus some small traveling-wave-like components.
      The observations of the dynamics of TM surface motion from this study will help
      us better understand the sound-receiving function of the TM and how it couples
      sound to the ossicular chain and inner ear.

PMID- 20034551
TI  - Anti-inflammatory and anti-arthritic activity of total flavonoids of the roots of
      Sophora flavescens.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Sophora flavescens have long been
      used in Chinese medicine for the treatment of fever, inflammatory disorders,
      ulcers and skin burns. Sophora flavescens contains flavonoids and alkaloids. AIM
      OF THE STUDY: This study was conducted to develop a plant-based anti-inflammatory
      agent focused on chronic inflammatory disorders. To accomplish this, the alkaloid
      free prenylated flavonoid-enriched fraction (PFS) of rhizomes of Sophora
      flavescens was prepared and its in vitro and in vivo anti-inflammatory activities
      were then evaluated for the first time. MATERIALS AND METHODS: The inhibitory
      activity of PFS on PGE(2), NO, IL-6 and TNF-alpha production of
      lipopolysaccharide (LPS)-treated RAW 264.7 cells was measured. Additionally,
      adjuvant-induced arthritis in rats was used as an animal model of chronic
      inflammation to establish the in vivo anti-inflammatory effects of PFS. RESULT:
      PFS inhibited cyclooxygenase-2 (COX-2)-catalyzed PGE(2) and inducible nitric
      oxide synthase (iNOS)-catalyzed NO production by lipopolysaccharide (LPS)-treated
      RAW 264.7 cells at 10-50 microg/ml, and these effects primarily occurred via COX
      2 inhibition and iNOS down-regulation, respectively. PFS also inhibited IL-6 and
      TNF-alpha production. When tested against adjuvant-induced arthritis in rats
      (chronic inflammation), PFS strongly inhibited arthritic inflammation when
      administered orally at doses of 10-100mg/kg/day. In addition, PFS administered
      orally potently inhibited acetic acid-induced writhing in mice. CONCLUSIONS: Our
      results suggest that PFS inhibits chronic inflammatory response and the
      inhibition of proinflammatory molecules such as COX-2, iNOS and IL-6 may
      contribute, at least in part, to the anti-inflammatory activity in vivo. Overall,
      these results indicate that PFS from Sophora flavescens may have the potential
      for treatment of chronic inflammatory disorders such as rheumatoid arthritis.

PMID- 20034552
TI  - Mechanisms of hematopoietic stem cell aging.
AB  - New blood cells are continually produced from the hematopoietic stem cells (HSCs)
      that reside in the bone marrow. Throughout the life-span of the organism, this
      stem cell reservoir sustains life. Although HSCs can persist in vivo longer than
      one life-span (Harrison et al., 1978), with aging, HSC regenerative potential
      diminishes and skewing from lymphopoiesis toward myelopoiesis occurs. The
      expansion in the HSC pool with aging provides sufficient, yet abnormal, blood
      production. Examination of gene expression changes in aged HSCs has provided a
      link between aging and genomic instability. Furthermore, studies on the effects
      of reactive oxygen species (ROS) on HSC aging has given more insight into the
      reasons for HSC failure. Understanding of the interactions between niche cells
      and HSCs and changes in them with aging, may give us insights into the lineage
      skewing phenotype observed in the aged, and also other immune dysfunctions.

PMID- 20034553
TI  - The promises and challenges of epigenetic epidemiology.
AB  - The union between epidemiology and epigenetics creates a new science that
      combines the strengths of both fields: the appropriate study design with adequate
      sample size to identify disease biomarkers and to uncover mechanistic pathways
      for environmental exposure and disease associations while controlling for
      confounding variables. Realization of the promises of epigenetic epidemiology
      requires overcoming some challenges in the design, conduct, and interpretation of
      epigenetic studies in human populations. These challenges include the choice of
      the appropriate tissue, confounding, misclassification, and effect modification.
      In particular, the tissue-specificity of epigenetic marks restricts epidemiologic
      studies of adequate size to easily accessible tissues.

PMID- 20034554
TI  - MicroRNA group disorganization in aging.
AB  - Among non-coding RNAs, microRNAs may be one of the best known subgroups, due to
      their unique function of negatively controlling gene expression, by either
      degrading target messages or binding to their 3'-untranslated region to inhibit
      translation. Thus gene expression can be repressed through post-transcriptional
      regulation, implemented as a 'dimmer switch', in contrast to the all-or-none mode
      of suppression. Work from our laboratory and others shows that during aging,
      dysregulated expression of microRNAs generally occurs in groups, suggesting that
      their actions may be functionally coordinated as a 'pack' by common
      transcriptional regulators; the accumulation of these 'pack' disorganizations may
      be the underlying culprit contributing to the pathoetiology of many age-dependent
      disease states. The fact that many microRNAs are coordinated in their expression,
      due to either the close proximity of their genomic locations or sharing the same
      transcriptional regulation, suggests that future strategies for correcting age
      dependent microRNA disorganization may need to involve a system biology, rather
      than a reductionist, approach. Therefore, understanding age-dependent changes of
      microRNA expression in 'packs' may open an entirely new frontier, i.e. how
      particular groups of non-coding RNAs, functioning together, contribute to
      mechanisms regulating aging and longevity.

PMID- 20034555
TI  - Epigenetics and aging.

PMID- 20034556
TI  - Calcitonin gene-related peptide immunoreactive neurons innervating the soft
      palate, the root of tongue, and the pharynx in the superior glossopharyngeal
      ganglion of the rat.
AB  - We have examined whether calcitonin gene-related peptide immunoreactive (CGRP-ir)
      neurons in the glossopharyngeal ganglia innervate the soft palate, the root of
      tongue, and the pharynx of the rat. Immunohistochemical observations revealed
      that numerous CGRP-ir neurons are located in the superior glossopharyngeal
      ganglion located ventrolateral to the medulla oblongata in the cranial cavity,
      and that CGRP-ir neurons are also located in the inferior glossopharyngeal
      ganglion at the jugular foramen. When Fluorogold was injected into the soft
      palate, the root of tongue, or the pharyngeal constrictor muscles, many
      retrogradely Fluorogold-labeled neurons were found in the superior
      glossopharyngeal ganglion and the nodose ganglion, and several Fluorogold-labeled
      neurons were found in the inferior glossopharyngeal ganglion. Double labeling
      with immunohistochemistry for CGRP and Fluorogold showed that in every case of
      injections of Fluorogold into the soft palate, the root of tongue, or the
      pharynx, about 30% of the Fluorogold-labeled neurons in the superior
      glossopharyngeal ganglion expressed CGRP-like immunoreactivity, while no double
      labeled neurons were found in the inferior glossopharyngeal ganglion or the
      nodose ganglion. These results indicate that nociceptive sensory information from
      the soft palate, the root of tongue, and the pharynx might be conveyed by the
      neurons in the superior glossopharyngeal ganglion to the nucleus tractus
      solitarii.

PMID- 20034557
TI  - Rapid loss of glutamine synthetase from astrocytes in response to hypoxia:
      implications for excitotoxicity.
AB  - We have examined brains of neonatal pigs that were rendered hypoxic. Glutamine
      synthetase (GS), a key enzyme in the detoxification of glutamate and ammonia, was
      rapidly lost from astrocytes in regions susceptible to damage, including the CA1
      of hippocampus and various cortical regions. Conversely, resilient areas such as
      the dentate gyrus exhibited little or no loss of GS. Onset of loss was rapid,
      patches of loss being evident by 1h post-insult, and loss was extensive by 24h
      and did not recover by 72 h. Examination of counterstained sections revealed that
      GS losses preceded any overt neuronal damage. Loss of GS from astrocytes would
      plausibly lead to a rise in intracellular glutamate, and could explain why
      reversal of astrocytic glutamate transport during hypoxia/ischaemia is
      conceptually possible.

PMID- 20034558
TI  - In vivo detection of inducible nitric oxide synthase in rodent gliomas.
AB  - Increased iNOS expression is often found in brain tumors, such as gliomas. The
      goal of this study was to develop and assess a novel molecular MRI (mMRI) probe
      for in vivo detection of iNOS in rodent models for gliomas (intracerebral
      implantation of rat C6 or RG2 cells or ethyl nitrosourea-induced glioma). The
      probe we used incorporated a Gd-DTPA (gadolinium(III) complex of
      diethylenetriamine-N,N,N',N'',N''-pentaacetate) backbone with albumin and biotin
      moieties and covalent binding of an anti-iNOS antibody (Ab) to albumin (anti-iNOS
      probe). We used mMRI with the anti-iNOS probe to detect in vivo iNOS levels in
      gliomas. Nonimmune normal rat IgG coupled to albumin-Gd-DTPA-biotin was used as a
      control nonspecific contrast agent. By targeting the biotin component of the anti
      iNOS probe with streptavidin Cy3, fluorescence imaging confirmed the specificity
      of the probe for iNOS in glioma tissue. iNOS levels in glioma tumors were also
      confirmed via Western blots and immunohistochemistry. The presence of plasma
      membrane-associated iNOS in glioma cells was established by transmission electron
      microscopy and gold-labeled anti-iNOS Ab. The more aggressive RG2 glioma was not
      found to have higher levels of iNOS compared to C6. Differences in glioma
      vascularization and blood-brain barrier permeability between the C6 and the RG2
      gliomas are discussed. In vivo assessment of iNOS levels associated with tumor
      development is quite feasible in heterogeneous tissues with mMRI.

PMID- 20034560
TI  - Indirubins deplete striatal monoamines in the Intact and MPTP-treated mouse brain
      and block kainate-induced striatal astrogliosis.
AB  - The indirubins long have been used in Chinese medicine for treatment of
      myelocytic leukemia. Among the many more recently described biological activities
      of the indirubins, attention has been directed toward the ability of these
      compounds to inhibit GSK-3 and CDKs, kinases implicated in neurodegenerative
      conditions. Little information is available on effects of indirubins on
      chemically-induced neurodegeneration. Here we examined the influence of three
      indirubins on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and kainic
      acid (KA)-induced neurotoxicity in the mouse. The three indirubins examined were
      6-bromoindirubin-3'-oxime (6BIO), 5-bromoindirubin-3'-oxime (5BIO) and 5-amino-6
      bromoindirubin (5A6BI). The first two derivatives were previously described
      indirubins with low nanomolar inhibitory activity against GSK-3 and CDKs. The
      third compound was synthesized by the dimerization of 5-amino-6-bromoisatin with
      3-acetoxyindol. The synthesis of the key compound 5-amino-6-bromoisatin was based
      on the bromination of the ketal of 5-amino-isatin. All indirubins examined
      decreased various measures associated with dopaminergic neurotransmission in
      striatum. These effects occurred alone or over and above the decrements seen
      following administration of the dopaminergic neurotoxicant, MPTP. Striatal
      serotonin and serotonin turnover were decreased by the indirubins in MPTP-treated
      mice. None of these striatal effects of the indirubins alone were associated with
      evidence of astrogliosis, an indicator of underlying neuropathology, nor did they
      potentiate the astrogliosis accompanying administration of MPTP. In general, the
      indirubins reduced KA-associated mortality and striatal but not hippocampal
      astrogliosis due to this toxicant. The data suggest that indirubins affect
      striatal biogenic amine levels and turnover in intact mice. The data do not
      indicate a neuroprotective action of indirubins in mice treated with MPTP but
      that they do suggest that they may be neuroprotective against KA-induced injury
      of the neostriatum.

PMID- 20034559
TI  - Behavioral sequelae following acute diisopropylfluorophosphate intoxication in
      rats: comparative effects of atropine and cannabinomimetics.
AB  - The comparative effects of atropine and the indirect cannabinomimetics URB597 (a
      fatty acid amide hydrolase inhibitor) and URB602 (a monoacylglycerol lipase
      inhibitor) on functional and neurobehavioral endpoints following acute
      diisopropylfluorophosphate intoxication were studied. Male Sprague-Dawley rats
      were treated with vehicle or DFP (2.5mg/kg, sc), immediately post-treated with
      either vehicle, atropine (16mg/kg), URB597 (3mg/kg), URB602 (10mg/kg) or a
      combination of URB597 and URB602, and functional signs of toxicity as well as
      nocturnal motor activity were measured daily for seven consecutive days.
      Performance in the elevated plus maze (for anxiety-like behavior) and the forced
      swimming test (for depression-like behavior) was measured at days 6-8 and 27-29
      after dosing. Twenty-four hours after dosing, DFP markedly reduced cholinesterase
      activity in selected brain regions and peripheral tissues (diaphragm and plasma).
      Substantial recovery of cholinesterase activity was noted at both 8 and 29days
      after dosing but significant inhibition was still noted in some brain regions at
      the latest time-point. DFP elicited body weight reductions and typical signs of
      cholinergic toxicity, and reduced nocturnal ambulation and rearing. Atropine and
      the cannabinomimetics (alone and in combination) partially attenuated DFP-induced
      functional signs of toxicity. None of the post-treatments reversed the DFP
      induced reduction in ambulation or rearing, however. No significant treatment
      related effects on elevated plus maze performance were noted. DFP-treated rats
      exhibited decreased swimming and increased immobility in the forced swimming test
      at both time-points. None of the post-treatments had any effect on DFP-induced
      changes in immobility or swimming at day 8. At day 29, atropine and the
      combination of URB597/URB602 significantly blocked DFP-induced changes in
      immobility, while URB597 and the combination reversed DFP-induced changes in
      swimming. The results suggest that early blockade of muscarinic receptors and
      enhancement of eCB signaling can attenuate both acute and delayed effects
      elicited by DFP.

PMID- 20034561
TI  - The 285 kDa Bap/RTX hybrid cell surface protein (SO4317) of Shewanella oneidensis
      MR-1 is a key mediator of biofilm formation.
AB  - Shewanella oneidensis, a Gram-negative bacterium with unusual respiratory
      versatility, is found in soil and sediment environments, and sporadically as an
      opportunistic pathogen in humans and aquatic animals. The ability to form
      biofilms is a critical factor in the environmental spread and survival of this
      bacterium. We subjected S. oneidensis MR-1 to random transposon insertion
      mutagenesis to identify genes contributing to the ability of the organism to form
      biofilms on polystyrene surfaces. Follow-up of the clone that was most heavily
      impaired in biofilm formation led to the identification of a novel 285 kDa multi
      domain protein which we have termed biofilm-promoting factor A (BpfA). BpfA is
      secreted by a type I secretion system to the cell surface, where it is a
      requisite for biofilm development. The BpfA-dependent biofilm phenotype is
      positively modulated by sub to low millimolar amounts of calcium. Intriguingly,
      BpfA features structural motifs and sequence fingerprints that can be traced back
      to bacterial Bap-family and RTX family proteins, two protein families harboring
      putative and established calcium binding sites.

PMID- 20034562
TI  - The PmrAB system in Erwinia amylovora renders the pathogen more susceptible to
      polymyxin B and more resistant to excess iron.
AB  - The PmrAB system is a two-component regulatory system that responds to
      extracellular iron and acidic pH. The role of the PmrAB system in Erwinia
      amylovora remains unknown so far. Our results showed that the pmrAB mutants were
      more resistant to strong acidic conditions than the wild type (WT) strain. The
      survival rate of the pmrAB mutants was much higher than that of WT when treated
      with polymyxin B. However, pmrAB mutants were more sensitive to extracellular
      iron than WT strain. These results demonstrated that the PmrAB system in E.
      amylovora renders the pathogen more susceptible to polymyxin B and acidic pH, but
      more resistance to excess iron.

PMID- 20034563
TI  - Chitosan-modified poly(D,L-lactide-co-glycolide) nanospheres for improving siRNA
      delivery and gene-silencing effects.
AB  - Chitosan (CS) surface-modified poly(D,L-lactide-co-glycolide) (PLGA) nanospheres
      (NS) for a siRNA delivery system were evaluated in vitro. siRNA-loaded PLGA NS
      were prepared by an emulsion solvent diffusion (ESD) method, and the
      physicochemical properties of NS were investigated. The level of targeted protein
      expression and siRNA uptake were examined in A549 cells. CS-modified PLGA NS
      exhibited much higher encapsulation efficiency than unmodified PLGA NS (plain
      PLGA NS). CS-modified PLGA NS showed a positive zeta potential, while plain-PLGA
      NS were negatively charged. siRNA uptake studies by observation with confocal
      laser scanning microscopy (CLSM) indicated that siRNA-loaded CS-modified PLGA NS
      were more effectively taken up by the cells than plain-PLGA NS. The efficiencies
      of different siRNA preparations were compared at the level of targeted protein
      expression. The gene-silencing efficiency of CS-modified PLGA NS was higher and
      more prolonged than those of plain-PLGA NS and naked siRNA. This result
      correlated with the CLSM studies, which may have been due to higher cellular
      uptake of CS-modified PLGA NS due to electrostatic interactions. It was concluded
      that CS-modified PLGA NS containing siRNA could provide an effective siRNA
      delivery system.

PMID- 20034565
TI  - Reduced function of the serotonin transporter is associated with decreased
      expression of BDNF in rodents as well as in humans.
AB  - In order to identify the molecular mechanisms that may contribute to the enhanced
      susceptibility to depression under serotonin transporter (SERT) dysfunction, we
      analyzed the expression of brain-derived neurotrophic factor (BDNF), a key player
      in neuronal plasticity, which is implicated in the etiology and treatment of
      depression. We found that BDNF levels were significantly reduced in the
      hippocampus and prefrontal cortex of SERT knockout rats, through transcriptional
      changes that affect different neurotrophin isoforms. The reduction of BDNF gene
      expression observed in prefrontal cortex is due, at least in part, to epigenetic
      changes that affect the promoter regions of exons IV and VI. Moreover, BDNF gene
      expression is also significantly reduced in leukocytes from healthy subjects
      carrying the S allele of the 5-HTTLPR, suggesting that the changes observed in
      SERT mutant rats may also be present in humans and may confer enhanced
      vulnerability to mood disorders.

PMID- 20034564
TI  - Infragranular gene expression disturbances in the prefrontal cortex in
      schizophrenia: signature of altered neural development?
AB  - The development of the human neocortex gives rise to a complex cytoarchitecture,
      grouping together cells with similar structure, connectivity and function. As a
      result, the six neocortical laminae show distinct molecular content. In
      schizophrenia, many anatomical and neurochemical changes appear to be restricted
      to a subset of lamina and/or cell types. In this study, we hypothesized that
      supragranular (SG; laminae II-III) and infragranular layers (IG; laminae V-VI) of
      area 46 in the human prefrontal cortex will show distinct and specific
      transcriptome alterations between subjects with schizophrenia and matched
      controls. To enhance sample homogeneity, we compared the gene expression patterns
      of the SG and IG layers of 8 matched middle-aged male subjects with schizophrenia
      to 8 pairwise matched controls using two replicate DNA microarrays for each
      sample. The study revealed strong disease-related laminar expression differences
      between the SG and IG layers. Expression changes were dominated by an overall
      underexpression of the IG-enriched genes in the schizophrenia subjects compared
      to normal control subjects. Furthermore, using a diagnosis-blind, unsupervised
      clustering of the control-derived SG or IG-enriched transcripts, the IG-enriched
      markers segregated the subjects with schizophrenia from the matched controls with
      a high degree of confidence. Importantly, multiple members of the semaphorin gene
      family reported altered gene expression, suggesting that the IG gene expression
      disturbances in subjects with schizophrenia may be a result of altered cortical
      development and disrupted brain connectivity.

PMID- 20034566
TI  - Dysfunctional mitochondria uphold calpain activation: contribution to Parkinson's
      disease pathology.
AB  - Calpain is a ubiquitous calcium-sensitive protease that is essential for normal
      physiologic neuronal function. However, mitochondrial-mediated-calcium
      homeostasis alterations may lead to its pathologic activation that jeopardizes
      neuronal structure and function. Here, we provide evidence to support a role for
      the involvement of calpain 1 in mitochondrial-induced neurodegeneration in a
      Parkinson's disease (PD) cellular model. We show that dysfunctional mitochondria
      increases cytosolic calcium, thereby, inducing calpain activation. Interestingly,
      its inhibition significantly attenuated the accumulation of alpha-synuclein
      oligomers and contributed to an increase of insoluble alpha-synuclein aggregates,
      known to be cytoprotective. Moreover, our data corroborate that calpain-1
      overactivation in our mitochondrial-deficient cells promote caspase-3 activation.
      Overall, our findings further clarify the crucial role of dysfunctional
      mitochondria in the control of molecular mechanisms occurring in PD brain cells,
      providing a potentially novel correlation between the degradation of calpain
      substrates suggesting a putative role of calpain and calpain inhibition as a
      therapeutic tool in PD.

PMID- 20034568
TI  - Runx3 is required for the specification of TrkC-expressing mechanoreceptive
      trigeminal ganglion neurons.
AB  - Sensory neurons project axons to specific peripheral and central targets
      according to their sensory modality. Runx3 is crucially involved in
      proprioceptive dorsal root ganglion neuron development. Runx3 is also expressed
      in trigeminal ganglion (TG) neurons. The role of Runx3 in the TG, however, is
      largely unknown because the TG does not contain proprioceptive neurons. In Runx3
      deficient (Runx3(-/-)) mice, TrkB-expressing TG neurons were increased, whereas
      TrkC-expressing TG neurons were decreased during TG neuron development. In Runx3(
      /-) neonatal mice, TrkC-expressing TG neurons did not project to the Merkel cells
      in the outer root sheath (ORS) of whisker vibrissae peripherally and the spinal
      trigeminal nucleus pars interpolaris (Sp5I) centrally. These findings suggest
      that Runx3 is required for the specification of TrkC-expressing TG neurons,
      conveying mechanoreceptive signals from the Merkel cells in the ORS of the
      whisker vibrissae to the Sp5I.

PMID- 20034567
TI  - Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in
      Alzheimer disease.
AB  - In an analysis of amyloid pathology in Alzheimer disease, we used an in situ
      approach to identify amyloid-beta (Abeta) accumulation and oxidative damage to
      nucleic acids in postmortem brain tissue of the hippocampal formation from
      subjects with Alzheimer disease. When carboxyl-terminal-specific antibodies
      directed against Abeta40 and Abeta42 were used for immunocytochemical analyses,
      Abeta42 was especially apparent within the neuronal cytoplasm, at sites not
      detected by the antibody specific to Abeta-oligomer. In comparison to the Abeta42
      positive neurons, neurons bearing oxidative damage to nucleic acids were more
      widely distributed in the hippocampus. Comparative density measurements of the
      immunoreactivity revealed that levels of intraneuronal Abeta42 were inversely
      correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized
      nucleoside (r=- 0.61, p<0.02). Together with recent evidence that the Abeta
      peptide can act as an antioxidant, these results suggest that intraneuronal
      accumulation of non-oligomeric Abeta may be a compensatory response in neurons to
      oxidative stress in Alzheimer disease.

PMID- 20034569
TI  - Single-step affinity purification of recombinant proteins using the silica
      binding Si-tag as a fusion partner.
AB  - We previously reported that a silica-binding protein, designated Si-tag, can be
      used as a fusion tag to immobilize functional proteins on silica surfaces. In
      this study, by taking advantage of the strong affinity of Si-tag for silica, we
      developed a single-step purification method for Si-tagged fusion proteins. We
      utilized unmodified bare silica particles as a specific adsorbent and a high
      concentration of MgCl(2) solution as an elution buffer. A fusion protein of Si
      tag and immunoglobulin-binding staphylococcal protein A, designated Si-tagged
      protein A, was recovered with a purity of 87+/-3% and yield of 84+/-4% from a
      crude extract of recombinant Escherichia coli. The simplicity of our method
      enables rapid, cost-effective purification of Si-tagged fusion proteins. We also
      discuss the mechanism of binding and dissociation of Si-tag and silica surfaces,
      and we suggest that the unusual basicity and disordered structure of the Si-tag
      polypeptide play important roles in the binding to silica.

PMID- 20034570
TI  - Anti-viral mechanism of barramundi Mx against betanodavirus involves the
      inhibition of viral RNA synthesis through the interference of RdRp.
AB  - Nervous necrosis virus (NNV) belongs to the betanodavirus of the Nodaviridae
      family. It is the causative agent of viral nervous necrosis (VNN) disease, and
      has inflicted devastating damage on the world-wide aquaculture industry. The fish
      that survived after the outbreak of VNN become persistently NNV-infected
      carriers. NNV-persistent infection has been demonstrated in a barramundi brain
      (BB) cell line, and it involves the type I interferon (IFN) response with the
      expression of Mx gene. However, little of the defense mechanism in fish cells
      against NNV infection is understood. In this study, the anti-NNV mechanism of
      barramundi Mx protein (BMx) was elucidated in cBB cells which were derived from
      BB cell line after serial treatments by NNV-specific antiserum and then became an
      NNV-free cell line. After NNV infection of cBB cells, the level of viral RNA
      dependent RNA polymerase (RdRp) increased with time over a period of 24 h post
      infection (hpi), but decreased when the BMx expression increased 48 and 72 hpi.
      When the expression of BMx was down-regulated by BMx-specific siRNA, the
      expression levels of viral RNA, proteins and progeny viral titers were restored.
      The BMx was found to colocalize with viral RdRp at the perinuclear area 24 hpi
      and coprecipitate with viral RdRp, indicating that they could bind with each
      other. Viral RdRp was also revealed to colocalize with lysosomes 48 hpi as the
      NNV RdRp level started to decline. Therefore, it is suggested that BMx inhibited
      the viral RNA synthesis by interaction with viral RdRp, and redistributed RdRp to
      perinuclear area for degradation.

PMID- 20034571
TI  - Cloning and expression of HSP70 gene of sipuncula Phascolosoma esculenta.
AB  - In this study the gene encoding HSP70 was isolated from Phascoloma esculenta by
      homologous cloning and rapid amplification of cDNA ends (RACE). The full-length
      of cDNA (2520 bp) consists of a 5'-terminal untranslated region (UTR) (125 bp), a
      3'-terminal UTR (421 bp) with a canonical polyadenylation signal sequence
      (AATAAA), a poly (A) tail, and an open reading frame (ORF) (1974 bp). The
      predicted molecular mass and isoelectric point for HSP70 is 71.6 kDa and 5.15,
      respectively. BLAST analysis showed that P. esculenta HSP70 gene shared high
      similarity. Classical HSP signature motifs, ATP/GTP-Binding Site Motif A,
      Bipartite Nuclear Targeting Sequence, the cytosolic HSP70 could be expressed in
      Escherichia coli BL21. After purification, the recombinant pET-HSP70 protein was
      used to produce the polyclonal antibody in mice and the specificity of the
      antibody was confirmed by Western blot analysis. Fluorescent real-time
      quantitative PCR analysis showed that expression of Hsp70 in sipuncula was
      increased significantly after exposure to 10 mM Zn for 12 h, Cd for 24 h, Cu for
      48 h, and was exposure to 37 degrees C for 24 h sea water.

PMID- 20034572
TI  - Immunocytochemical localization of piscidin in mast cells of infected seabass
      gill.
AB  - Annual losses of approximately 5-10% of the juvenile stock of European seabass,
      Dicentrarchus labrax (L.) in the northern coast of the Adriatic Sea has been
      attributed to heavy infections of the gill monogenean Diplectanum aequans.
      Immunocytochemical, light and ultrastructural studies were carried out on seabass
      naturally parasitized with this monogenean. The site of the worm's attachment was
      marked by the common presence of haemorrhages and white mucoid exudate. In
      histological sections, infected gills showed hyperplasia, as well as
      proliferation of mucous cells and rodlet cells. Disruption and fusion of the
      secondary lamellae were common in all infected seabass, with several specimens
      also showing marked inflammation and erosion of the primary and secondary
      lamellar epithelium. Immunostaining of primary and secondary gill filaments with
      an antibody against the antimicrobial peptide piscidin 3 (anti-piscidin 3
      antibody, anti-HAGR) revealed a subpopulation of mast cells that were positive.
      Mast cells were both within and outside the blood vessels of the primary and
      secondary lamellae, and often made intimate contact with vascular endothelial
      cells. Mast cells were irregular in shape with a cytoplasm filled by numerous
      electron-dense, membrane-bound granules. Our data provide evidence showing the
      presence of piscidin 3 in the cytoplasmic granules of an important group of fish
      inflammatory cells, the mast cells resident in seabass gill tissue. There was no
      significant difference in the number of HAGR-positive mast cells between infected
      and uninfected fish (ANOVA, p > 0.05). However, mast cells in parasitized gills
      usually showed much stronger immunostaining intensity compared to those in
      unparasitized gills. These data are the first to document a response of piscidins
      or any other antimicrobial peptide of fish to parasite infection and suggest that
      mast cells may play a role in certain inflammatory responses without a detectable
      increase in their numbers.

PMID- 20034573
TI  - Studies on the immunomodulatory effect of polysaccharide gel extracted from Durio
      zibethinus in Penaeus monodon shrimp against Vibrio harveyi and WSSV.
AB  - Oral administration of polysaccharide gel (PG) in shrimp diets revealed
      immunostimulating potential and disease resistance in Penaeus monodon (black
      tiger shrimp). PG from the fruit-rind of Durio zibethinus has been characterized
      to be a pectic polysaccharide with immunomodulating and antibacterial activities.
      PG inhibited growth of the shrimp bacterial pathogen, Vibrio harveyi 1526, by
      agar diffusion and broth microdilution tests. Clear inhibition zones on agar
      plates were observed at the lowest PG concentration of 3.1 mg/ml, where minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)
      values for PG were 6.3 and 12.5 mg/ml, respectively. Each group of juvenile
      shrimps, initial mean body weight 0.29 +/- 0.04 g, was housed in a closed
      recirculating treated water system and was fed with PG-supplemented diets
      containing 1, 2 and 3% PG or shrimp basal diet in the control group for 8 and 12
      weeks. PG-supplemented diets did not contribute to the overall growth of black
      tiger shrimp. The immune response was evaluated by analysis of prophenoloxidase
      activity and total hemocyte count in the shrimp fed PG-supplemented diets for 12
      weeks. Prophenoloxidase activity in shrimp fed the 1, 2 and 3% PG-supplemented
      diet and total hemocyte count in shrimp fed the 1 and 2% PG-supplemented diet
      were higher (P < 0.05) than those of the control group. The percent survival was
      higher in groups fed the 1-3% PG-supplemented diets in challenge tests with
      either white spot syndrome virus (WSSV) or the bacterium V. harveyi 1526 than
      that of the control group. Relative percent survival (RPS) values in groups fed
      the 2% PG-supplemented diet showed the highest RPS value for disease resistance
      of 100% (at Day 6) and 36% (at Day 4) in treated shrimp against viral and
      bacterial infection, respectively. Mortality of PG-supplemented diets in treated
      shrimps against WSSV infection was also found to be much lower (P < 0.05) than
      that of the control group.

PMID- 20034574
TI  - Effects of mannan oligosaccharide dietary supplementation on performances of the
      tropical spiny lobsters juvenile (Panulirus ornatus, Fabricius 1798).
AB  - The effects of dietary mannan oligosaccharide (MOS) (Bio-Mos, Alltech, USA) on
      the growth, survival, physiology, bacteria and morphology of the gut and immune
      response to bacterial infection of tropical rock lobsters (Panulirus ornatus)
      juvenile were investigated. Dietary inclusion level of MOS at 0.4% was tested
      against the control diet (trash fish) without MOS inclusion. At the end of 56
      days of rearing period, a challenged test was also conducted to evaluate the
      bacterial infection resistant ability of the lobsters fed the two diets. Lobster
      juvenile fed MOS diet attained 2.86 +/- 0.07 g of total weigh and 66.67 +/- 4.76%
      survival rate which were higher (P < 0.05) than the lobsters fed control diet
      (2.35 +/- 0.14 g total weight and 54.76 +/- 2.38% survival rate, respectively)
      thus providing the higher (P < 0.05) specific growth rate (SGR) and average
      weekly gain (AWG) of lobsters fed MOS diet. Physiological condition indicators
      such as wet tail muscle index (Tw/B), wet hepatosomatic index (Hiw) and dry tail
      muscle index (Td/B) of the lobsters fed MOS supplemented diet were higher (P <
      0.05) than that of the lobsters fed the control diet. Bacteria in the gut (both
      total aerobic and Vibrio spp.) and gut's absorption surface indicated by the
      internal perimeter/external perimeter ratio were also higher (P < 0.05) when the
      lobsters were fed MOS diet. Lobsters fed MOS diet were in better immune condition
      showed by higher THC and GC, and lower bacteraemia. Survival, THC, GC were not
      different among the lobsters fed either MOS or control diet after 3 days of
      bacterial infection while bacteraemia was lower in the lobsters fed MOS diet.
      After 7 days of bacterial infection the lobsters fed MOS diet showed higher
      survival, THC, GC and lower bacteraemia than the lobsters fed the control diet.
      The experimental trial demonstrated the ability of MOS to improve the growth
      performance, survival, physiological condition, gut health and immune responses
      of tropical spiny lobsters juveniles.

PMID- 20034575
TI  - Sequence analysis, characterization and tissue distribution of channel catfish
      (Ictalurus punctatus Rafinesque, 1818) myeloperoxidase cDNA.
AB  - Myeloperoxidase (EC 1.11.1.7), a heme-containing lysosomal glycoprotein, is found
      predominantly in azurophilic granules of neutrophils. This enzyme upon activation
      catalyzes hydrogen peroxide in the presence of various halide ions to form
      hypohalous acids. Subsequently, these reagents are able to kill the invading
      microorganisms. In this study, we report the identification, characterization and
      expression analysis of the channel catfish myeloperoxidase transcript. The full
      length nucleotide sequence of channel catfish myeloperoxidase cDNA had 3157
      nucleotides, including an open reading frame, which appears to encode a putative
      peptide of 771 amino acid residues with a calculated molecular mass of 87.14 kDa.
      By comparison with the human counterpart, the channel catfish myeloperoxidase
      peptide can be divided into domains and has conservative features, including
      peroxidase catalytic sites, covalent linkage sites for the heme group and all
      cysteine residues. The channel catfish myeloperoxidase transcript was detected by
      RT-PCR in anterior kidneys, where the major leukocyte population is neutrophil
      precursors. Reagent development and the role of this enzyme in Edwardsiella
      ictaluri infection are under investigation.

PMID- 20034576
TI  - Immunogenic and protective effects of an oral DNA vaccine against infectious
      pancreatic necrosis virus in fish.
AB  - DNA vaccines and oral DNA-based immunotherapy against infectious pancreatic
      necrosis virus (IPNV) have scarcely been studied in salmonid fish. Here, a vector
      with the capsid VP2 gene inserted was encapsulated in alginate microspheres to
      avoid the aggressive gastrointestinal conditions experienced following oral
      administration. Alginate microspheres were effective to protect the pDNA encoding
      VP2, which was expressed early in different organs of the vaccinated trout and
      that persisted for at least 60 days. The vaccine induces innate immune responses,
      raising the expression of IFN more than 10-fold relative to the fish vaccinated
      with the empty plasmid, at 7 and 15 days post-vaccination. Likewise, maximal
      expression of the IFN-induced antiviral Mx protein was recorded 15 days post
      vaccination and neutralizing antibodies were also detected after 15 days,
      although their titre rose further at 21 days post-vaccination. Protection was
      high in the immunized fish, which showed around an 80% relative survival when
      challenged 15 and 30 days after vaccine delivery. Very low viral load with
      respect to the control group was detected in the vaccinated fish that survived 45
      days after challenge. Thus, this study demonstrates the potential of the
      encapsulation technique for IPNV-DNA vaccine delivery and the relevance of the
      IPNV-VP2 gene for future plasmid constructs.

PMID- 20034577
TI  - Gene cloning and characterization of ferritin H and M subunits from large yellow
      croaker (Pseudosciaena crocea).
AB  - Ferritin, an iron-binding protein, plays a role in host immune response to
      invading stimulus. Two ferritin subunit cDNAs, lycfh and lycfm, were identified
      from large yellow croaker, Pseudosciaena crocea. Analysis of the lycfh and lycfm
      5'-UTR showed that both had a putative iron responsive element (IRE). Amino acid
      sequence alignment and phylogenetic analysis indicated that LycfH and LycfM had
      high identity to H and M type subunit of vertebrate ferritins respectively, while
      both of them showed the low identity to L type subunit. In all eight tissues
      examined, lycfh and lycfm expressions were detectable on transcriptional level.
      Real-time PCR assay indicated that the transcriptional levels of lycfh and lycfm
      were significantly increased in liver, spleen and kidney of the fish stimulated
      by attenuated live Vibrio anguillarum strain. Furthermore, ferritin subunit H and
      M were probably two candidates of immune molecules involved in acute phase
      response in large yellow croaker because their transcriptional levels were
      quickly increased and reached the peak levels at 12 h in liver after challenged
      with bacteria.

PMID- 20034578
TI  - Real versus imagined locomotion: a [18F]-FDG PET-fMRI comparison.
AB  - The cortical, cerebellar and brainstem BOLD-signal changes have been identified
      with fMRI in humans during mental imagery of walking. In this study the whole
      brain activation and deactivation pattern during real locomotion was investigated
      by [(18)F]-FDG-PET and compared to BOLD-signal changes during imagined locomotion
      in the same subjects using fMRI. Sixteen healthy subjects were scanned at
      locomotion and rest with [(18)F]-FDG-PET. In the locomotion paradigm subjects
      walked at constant velocity for 10 min. Then [(18)F]-FDG was injected
      intravenously while subjects continued walking for another 10 min. For comparison
      fMRI was performed in the same subjects during imagined walking. During real and
      imagined locomotion a basic locomotion network including activations in the
      frontal cortex, cerebellum, pontomesencephalic tegmentum, parahippocampal,
      fusiform and occipital gyri, and deactivations in the multisensory vestibular
      cortices (esp. superior temporal gyrus, inferior parietal lobule) was shown. As a
      difference, the primary motor and somatosensory cortices were activated during
      real locomotion as distinct to the supplementary motor cortex and basal ganglia
      during imagined locomotion. Activations of the brainstem locomotor centers were
      more prominent in imagined locomotion. In conclusion, basic activation and
      deactivation patterns of real locomotion correspond to that of imagined
      locomotion. The differences may be due to distinct patterns of locomotion tested.
      Contrary to constant velocity real locomotion (10 min) in [(18)F]-FDG-PET, mental
      imagery of locomotion over repeated 20-s periods includes gait initiation and
      velocity changes. Real steady-state locomotion seems to use a direct pathway via
      the primary motor cortex, whereas imagined modulatory locomotion an indirect
      pathway via a supplementary motor cortex and basal ganglia loop.

PMID- 20034579
TI  - Robust atrophy rate measurement in Alzheimer's disease using multi-site serial
      MRI: tissue-specific intensity normalization and parameter selection.
AB  - We describe an improved method of measuring brain atrophy rates from serial MRI
      for multi-site imaging studies of Alzheimer's disease (AD). The method (referred
      to as KN-BSI) improves an existing brain atrophy measurement technique-the
      boundary shift integral (classic-BSI), by performing tissue-specific intensity
      normalization and parameter selection. We applied KN-BSI to measure brain atrophy
      rates of 200 normal and 141 AD subjects using baseline and 1-year MRI scans
      downloaded from the Alzheimer's Disease Neuroimaging Initiative database.
      Baseline and repeat images were reviewed as pairs by expert raters and given
      quality scores. Including all image pairs, regardless of quality score, mean KN
      BSI atrophy rates were 0.09% higher (95% CI 0.03% to 0.16%, p=0.007) than classic
      BSI rates in controls and 0.07% higher (-0.01% to 0.16%, p=0.07) higher in ADs.
      The SD of the KN-BSI rates was 22% lower (15% to 29%, p<0.001) in controls and
      13% lower (6% to 20%, p=0.001) in ADs, compared to classic-BSI. Using these
      results, the estimated sample size (needed per treatment arm) for a hypothetical
      trial of a treatment for AD (80% power, 5% significance to detect a 25% reduction
      in atrophy rate) would be reduced from 120 to 81 (a 32% reduction, 95% CI=18% to
      45%, p<0.001) when using KN-BSI instead of classic-BSI. We concluded that KN-BSI
      offers more robust brain atrophy measurement than classic-BSI and substantially
      reduces sample sizes needed in clinical trials.

PMID- 20034581
TI  - Computational modeling of high-frequency oscillations at the onset of neocortical
      partial seizures: from 'altered structure' to 'dysfunction'.
AB  - In this paper, a neural mass model is proposed to analyze some mechanisms
      underlying the generation of fast oscillations (80 Hz and beyond) at the onset of
      seizures. This model includes one sub-population of pyramidal cells and one sub
      population of interneurons targeting the perisomatic region of pyramidal cells
      where fast GABAergic currents are mediated. We identified some conditions for
      which the model can reproduce the features of high-frequency, chirp-like (from
      approximately 100 to approximately 70 Hz) signatures observed in real depth-EEG
      signals recorded in epileptic patients at seizure onset ("fast onset activity").
      These conditions included appropriate alterations in (i) the strengths of
      GABAergic and glutamatergic connections, and (ii) the amplitude of average
      EPSPs/IPSPs. Results revealed that a subtle balance between excitatory and
      inhibitory feedbacks is required in the model for reproducing a 'realistic' fast
      activity, i.e., showing a reduction of frequency with a simultaneous increase in
      amplitude, as actually observed in epileptogenic cerebral cortex. Results also
      demonstrated that the number of scenarios (variation, in time, of model
      parameters) leading to chirp-like signatures was rather limited. First, to
      produce high-frequency output signals, the model should operate in a "resonance"
      region, at the frontier between a stable and an unstable region. Second both EPSP
      and IPSP amplitudes should decrease with time in order to obey the
      frequency/amplitude constraint. These scenarios obtained through a mathematical
      analysis of the model show how some alteration in the structure of neural
      networks can lead to dysfunction. They also provide insights into potentially
      important mechanisms for high-frequency epileptic activity generation.

PMID- 20034580
TI  - The test-retest reliability of 18F-DOPA PET in assessing striatal and
      extrastriatal presynaptic dopaminergic function.
AB  - Brain presynaptic dopaminergic function can be assessed using 18F-DOPA positron
      emission tomography (PET). Regional 18F-DOPA utilization may be used to index
      dopaminergic abnormalities over time or dopaminergic response to treatment in
      clinical populations. Such studies require prior knowledge of the stability of
      the 18F-DOPA signal in the brain regions of interest. Test-retest reliability was
      examined in eight healthy volunteers who each received two 18F-DOPA PET scans,
      approximately 2 years apart. 18F-DOPA utilization (k(i)(cer)) was determined
      using graphical analysis relative to a reference tissue input (Patlak and
      Blasberg, 1985). Reproducibility (measured as the within-subjects variation) and
      reliability (measured as intraclass correlation coefficients, ICCs) of 18F-DOPA
      k(i)(cer) were assessed in the structural and functional subdivisions of the
      striatum and select extrastriatal brain regions. Voxel-based median ICC maps were
      used to visualize the distribution of 18F-DOPA k(i)(cer) reliability across the
      brain. The caudate and putamen, and associative and sensorimotor, striatal
      subdivisions showed good reliability across the two scan sessions with bilateral
      ICCs ranging from 0.681 to 0.944. Reliability was generally lower in
      extrastriatal regions, with bilateral ICCs ranging from 0.235 in the amygdala to
      0.894 in the thalamus. These data confirm the utility of 18F-DOPA PET in
      assessing dopaminergic function in the striatum and select extrastriatal areas
      but highlight the limitations in using this approach to measure dopaminergic
      function in low uptake extrastriatal brain areas. This information can be used to
      optimize the experimental design of future studies investigating changes in brain
      dopaminergic function with 18F-DOPA.

PMID- 20034582
TI  - fMRI-adaptation evidence of overlapping neural representations for objects
      related in function or manipulation.
AB  - Sensorimotor-based theories of semantic memory contend that semantic information
      about an object is represented in the neural substrate invoked when we perceive
      or interact with it. We used fMRI adaptation to test this prediction, measuring
      brain activation as participants read pairs of words. Pairs shared function
      (flashlight-lantern), shape (marble-grape), both (pencil-pen), were unrelated
      (saucer-needle), or were identical (drill-drill). We observed adaptation for
      pairs with both function and shape similarity in left premotor cortex. Further,
      degree of function similarity was correlated with adaptation in three regions:
      two in the left temporal lobe (left medial temporal lobe, left middle temporal
      gyrus), which has been hypothesized to play a role in mutimodal integration, and
      one in left superior frontal gyrus. We also found that degree of manipulation
      (i.e., action) and function similarity were both correlated with adaptation in
      two regions: left premotor cortex and left intraparietal sulcus (involved in
      guiding actions). Additional considerations suggest that the adaptation in these
      two regions was driven by manipulation similarity alone; thus, these results
      imply that manipulation information about objects is encoded in brain regions
      involved in performing or guiding actions. Unexpectedly, these same two regions
      showed increased activation (rather than adaptation) for objects similar in
      shape. Overall, we found evidence (in the form of adaptation) that objects that
      share semantic features have overlapping representations. Further, the particular
      regions of overlap provide support for the existence of both sensorimotor and
      amodal/multimodal representations.

PMID- 20034583
TI  - Microscopic diffusion tensor imaging of the mouse brain.
AB  - Diffusion tensor imaging (DTI) data at 43 mum isotropic resolution has been
      acquired on the intact adult mouse brain in 28-h scan time by using a streamlined
      protocol, including specimen fixation and staining, image acquisition,
      reconstruction, post-processing, and distribution. An intermediate registration
      of each component image is required to achieve the desired microscopic
      resolution. Multiple parameters have been derived, including fractional
      anisotropy, axial and radial diffusivity, and a color-coded orientation map of
      the primary eigenvector. Each DTI dataset was mapped to a common reference space
      to facilitate future standardized analysis. Fiber tracking has also been
      demonstrated, providing 3D connection information. This protocol to acquire high
      resolution DTI data in a robust and repeatable fashion will serve as a foundation
      to quantitatively study mouse brain integrity and white matter architecture, at
      what we believe to be the highest spatial resolution yet attained.

PMID- 20034584
TI  - Complex patterns of continental speciation: molecular phylogenetics and
      biogeography of sub-Saharan puddle frogs (Phrynobatrachus).
AB  - Puddle frogs (Anura: Phrynobatrachidae) are one of the most species-rich sub
      Saharan amphibian groups, occupying an extraordinarily diverse range of habitats.
      We construct the first phylogeny of puddle frogs, utilizing mitochondrial (12S
      rRNA, valine-tRNA, and 16S rRNA) and nuclear (RAG-1) DNA. Phylogenetic analyses
      are conducted using separate and combined partitions under maximum parsimony,
      maximum likelihood, and Bayesian criterion. Monophyly of the Phrynobatrachidae is
      well supported, and three major clades of Phrynobatrachus are identified. We
      reconstructed a biogeographic history using habitat preference, elevation, and
      geographic distribution. Habitat niches appear to be conserved between sister
      species, with the majority of species favoring forest over savanna habitats and
      the most recent common ancestor of the Phrynobatrachidae reconstructed as a
      forest species. Analyses of elevational data identify three independent
      colonizations of highland regions, one in each of the three major clades.
      Ancestral reconstructions support an East African origination of puddle frogs.
      Most species are restricted to one of five sub-Saharan regions and are
      distributed within the Eastern, Central, and Western zones with far fewer species
      in Southern Africa. These results elucidate the complex patterns of spatial niche
      partitioning that have contributed to the diversification of this widely
      distributed, sub-Saharan genus.

PMID- 20034585
TI  - Characterization of Ctr family genes and the elucidation of their role in the
      life cycle of Neurospora crassa.
AB  - Transcriptional analysis using qRT-PCR of 62 metal ion transporters during
      conidial germination of Neurospora crassa showed a significant up regulation of a
      hypothetical copper transporter gene, tcu-1, that belongs to the Ctr family.
      Herein we characterised the Ctr family genes (tcu-1, tcu-2 and tcu-3) and
      deciphered their role in various developmental phases of the N. crassa life
      cycle. Cross complementation assays in copper uptake mutant of Saccharomyces
      cerevisiae revealed that tcu-1, tcu-2 and tcu-3 are functional homologs of S.
      cerevisiae copper transporters. Expression studies of Ctr family members in
      various developmental phases of N. crassa showed differential expression pattern
      for high-affinity copper transporter, TCU1. Functional analysis of their gene
      knockout mutants showed that tcu-1 is essential for saprophytic conidial
      germination, vegetative growth and perithecia development under copper limited
      conditions while conidiation remained unaffected.

PMID- 20034586
TI  - Localization and function of calmodulin in live-cells of Aspergillus nidulans.
AB  - Calmodulin (CaM) is a small, eukaryotic protein that reversibly binds Ca(2+).
      Study of CaM localization in genetically tractable organisms has yielded many
      insights into CaM function. Here, we described the dynamic localization of
      Aspergillus nidulans CaM (AnCaM) in live-cells by using recombination strains
      with homologous, single cross-over insertions at the target gene which placed the
      GFP fused copy under the inducible alcA promoter and the RFP-CaM integration
      under the native cam promoter. We found that the localization of CaM fusion was
      quite dynamic throughout the hypha and was concentrated to the active growing
      sites during germination, hyphal growth, cytokinesis and conidiation. The
      depletion of CaM by alcA promoter repression induced the explicit abnormalities
      of germlings with the swollen germ tubes. In addition, the position of highly
      concentrated GFP-CaM in the extreme apex seemed to determine the hyphal
      orientation. These data collectively suggest that CaM is constantly required for
      new hyphal growth. In contrast to this constant accumulation at the apex, GFP-CaM
      was only transiently localized at septum sites during cytokinesis. Notably,
      depletion of CaM caused the defect of septation with a completely blocked septum
      formation indicating that the transient CaM accumulation at the septum site is
      essential for septation. Moreover, the normal localization of CaM at a hyphal tip
      required the presence of the functional actin cytoskeleton and the motor protein
      KipA, which is indispensable for positioning Spitzenkorper. This is the first
      report of CaM localization and function in live-cells by the site-specific
      homologous integration in filamentous fungi.

PMID- 20034587
TI  - Acquired immune response to defined Plasmodium vivax antigens in individuals
      residing in northern India.
AB  - In this investigation, we evaluated the naturally acquired immune response to
      Plasmodium vivax stage-specific antigens in individuals of different age groups
      belonging to malaria endemic areas of northern India. Four synthetic peptides
      containing both B- and T-cell epitopes from P. vivax circumsporozoite protein,
      merozoite surface protein-1, apical membrane antigen-1 and gametocyte surface
      antigen-1 were used to determine both humoral and cellular immune responses.
      Immunity, in terms of antibody response and T-cell proliferation against these
      stage-specific peptides, has been observed in the study subjects. The results
      demonstrated age-dependent antibody response in this population. Forty two
      patients were diagnosed with P. vivax. There was a significant association
      (P=0.013) between number of antibody responders and recognition of stage-specific
      epitopes by antibodies. The antibody response to B-epitopes of P. vivax CSP,
      MSP1, AMA1 and GAM1 was associated with age; adults responded more frequently to
      these antigens than did younger children. In this population, 66% (201/304) cases
      showed seropositivity to all peptides and 13% (41/304) showed negative response.
      Peripheral blood mononuclear cells of more than 75% of individuals proliferated
      in response to stimulation by all four epitopes. In conclusion, the results
      demonstrated immunogenicity of the epitopes to P. vivax in population of this
      endemic zone.

PMID- 20034588
TI  - Recent insight into the pathogenicity mechanisms of the emergent pathogen
      Photorhabdus asymbiotica.
AB  - Photorhabdus asymbiotica is unique among the entomopathogenic bacteria of this
      genus in also being able to infect humans, leading to its isolation from some
      clinical samples. Recent comparative genomics data and the results of studies of
      interactions between bacteria and cells provide insight into the adaptation of
      this bacterium to its new niche, the human body.

PMID- 20034589
TI  - CD8+ cells protect mice against reinfection with the intestinal parasite Eimeria
      falciformis.
AB  - We investigated cellular immune responses of mice infected with the apicomplexan
      parasite Eimeria falciformis in order to characterise protective immune
      mechanisms and effector functions. Adoptive transfer experiments with mesenterial
      lymph node cells (MLNC) from immune donor mice were performed, and the oocyst
      output monitored after challenge infection. Phenotypical analysis by fluorescence
      cytometry and T cell proliferation assay showed that already from day four post
      infection E. falciformis-specific lymphocytes were present in the MLN. The
      frequency of parasite-specific, IFN-gamma producing CD4+ and CD8+ cells increased
      in this period by 9.8% and 16.4%, respectively. Infection experiments with IFN
      gamma deficient mice revealed that IFN-gamma is involved in resistance to primary
      and secondary infection. Transfer of total MLNC from immune donors reduced the
      oocyst output by 65-74%, as compared to the oocyst output of animals transferred
      with cells from naive donors. Transfer of CD8+ cells inhibited parasite
      development resulting in a reduction of oocyst numbers by 42-64%, whereas CD4+
      cells showed no influence on resistance to reinfection.

PMID- 20034591
TI  - Studying the cyto-genotoxic effects of 12 cigarette smoke condensates on human
      lymphoblastoid cell line in vitro.
AB  - In the present study, the cyto-genotoxic effects of 12 CSCs prepared from a
      diverse set of cigarettes on human B lymphoblastoid cells were compared using
      five in vitro assays. The cells were exposed to CSCs at doses of 2.5, 5.0, 7.5,
      10.0, and 12.5 x 10(-3)cigarette/ml for 24h in neutral red uptake and CCK-8
      assays, at doses of 1.0, 2.0, 3.0, 4.0, and 5.0 x 10(-3)cigarette/ml for 3h in
      cell apoptosis assay, at doses of 6.0, 8.0, 10.0, 12.0, and 14.0 x 10(
      3)cigarette/ml for 4h in comet assay, and at doses of 1.0, 2.0, 4.0, 6.0, and 8.0
      x 10(-3)cigarette/ml for 4h in micronucleus assay. The potency of 12 CSCs to
      induce corresponding toxic effects in each assay was calculated, and the
      correlations between the results in five assays were analyzed. Our investigation
      showed that the results of 12 CSCs in CCK-8 and cell apoptosis assays were
      positive, the results of 11 CSCs in neutral red uptake and comet assays were
      positive, and 9 CSCs could induce significantly the micronuclei in micronucleus
      assay. It was found that the potency to induce the cytotoxic effects among 12
      CSCs ranged 9.694 folds in neutral red uptake assay and 6.43 folds in CCK-8
      assay, the potency to induce cell apoptosis among 12 CSCs ranged 8.191 folds, the
      potency to induce DNA damage among 12 CSCs ranged 29.199 folds, the potency to
      induce micronuclei among 12 CSCs ranged 5.879 folds. Moreover, the good
      correlations were found between any two assays. It was suggested that the cyto
      genotoxicity of CSCs from different brands of cigarettes varied greatly, comet
      assay might be a sensitive assay in assessing the genotoxicity induced by CSCs.

PMID- 20034590
TI  - Human circulating fibrocytes have the capacity to differentiate osteoblasts and
      chondrocytes.
AB  - Fibrocytes are bone marrow-derived cells. Fibrocytes can differentiate into
      adipocyte- and myofibroblast-like cells. Since fibrocytes can behave like
      mesenchymal progenitor cells, we hypothesized that fibrocytes have the potential
      to differentiate into other mesenchymal lineage cells, such as osteoblasts and
      chondrocytes. In this study, we found that fibrocytes differentiated into
      osteoblast-like cells when cultured in osteogenic media in a manner similar to
      osteoblast precursor cells. Under these conditions, fibrocytes and osteoblast
      precursor cells displayed increased calcium deposition, and increased expression
      of specific osteogenic genes. In addition, dephosphorylation of cAMP-responsive
      element binding protein was associated with the increased ratio of receptor
      activator of the NF-kappaB Ligand/osteoprotegerin gene expression and enhanced
      gene expression of osterix in these cells under these conditions. Both events are
      important in promoting osteogenesis. In contrast, fibrocytes and mesenchymal stem
      cells cultured in chondrogenic media in the presence of transforming growth
      factor-beta3 were found to differentiate to chondrocyte-like cells. Fibrocytes
      and mesenchymal stem cells under these conditions were found to express increased
      levels of aggrecan and type II collagen genes. Transcription factor genes
      associated with chondrogenesis were also found to be induced in fibrocytes and
      mesenchymal stem cells under these conditions. In contrast, beta-catenin protein
      and the core binding factor alpha1 subunit protein transcription factor were
      decreased in expression under these conditions. These data indicate that human
      fibrocytes have the capability to differentiate into osteoblast- and chondrocyte
      like cells. These findings suggest that such cells could be used in cell-based
      tissue-regenerative therapy.

PMID- 20034592
TI  - Effects of pulsed, spatially fractionated, microscopic synchrotron X-ray beams on
      normal and tumoral brain tissue.
AB  - Microbeam radiation therapy (MRT) uses highly collimated, quasi-parallel arrays
      of X-ray microbeams of 50-600keV, produced by third generation synchrotron
      sources, such as the European Synchrotron Radiation Facility (ESRF), in France.
      The main advantages of highly brilliant synchrotron sources are an extremely high
      dose rate and very small beam divergence. High dose rates are necessary to
      deliver therapeutic doses in microscopic volumes, to avoid spreading of the
      microbeams by cardiosynchronous movement of the tissues. The minimal beam
      divergence results in the advantage of steeper dose gradients delivered to a
      tumor target, thus achieving a higher dose deposition in the target volume in
      fractions of seconds, with a sharper penumbra than that produced in conventional
      radiotherapy. MRT research over the past 20 years has yielded many results from
      preclinical trials based on different animal models, including mice, rats,
      piglets and rabbits. Typically, MRT uses arrays of narrow ( approximately 25-100
      microm wide) microplanar beams separated by wider (100-400 microm centre-to
      centre) microplanar spaces. The height of these microbeams typically varies from
      1 to 100 mm, depending on the target and the desired preselected field size to be
      irradiated. Peak entrance doses of several hundreds of Gy are surprisingly well
      tolerated by normal tissues, up to approximately 2 yr after irradiation, and at
      the same time show a preferential damage of malignant tumor tissues; these
      effects of MRT have now been extensively studied over nearly two decades. More
      recently, some biological in vivo effects of synchrotron X-ray beams in the
      millimeter range (0.68-0.95 mm, centre-to-centre distances 1.2-4 mm), which may
      differ to some extent from those of microscopic beams, have been followed up to
      approximately 7 months after irradiation. Comparisons between broad-beam
      irradiation and MRT indicate a higher tumor control for the same sparing of
      normal tissue in the latter, even if a substantial fraction of tumor cells are
      not receiving a radiotoxic level of radiation. The hypothesis of a selective
      radiovulnerability of the tumor vasculature versus normal blood vessels by MRT,
      and of the cellular and molecular mechanisms involved remains under
      investigation. The paper highlights the history of MRT including salient
      biological findings after microbeam irradiation with emphasis on the vascular
      components and the tolerance of the central nervous system. Details on
      experimental and theoretical dosimetry of microbeams, core issues and possible
      therapeutic applications of MRT are presented.

PMID- 20034593
TI  - The use of PIG-A as a sentinel gene for the study of the somatic mutation rate
      and of mutagenic agents in vivo.
AB  - Mutations are an inherent risk of cell duplication. On one hand, inheritable
      mutations are the driving force of biological evolution; on the other hand, their
      accumulation in somatic cells plays a key role in the development of cancer. The
      frequency of mutants (f) and the rate of mutation (mu) are biological features of
      any cell population: their measurement could provide important information about
      the risk of oncogenesis and the exposure to carcinogenic agents. However, the
      measurement of these parameters is not trivial. To measure f and mu, a potential
      sentinel gene is the PIG-A gene, which encodes one of the subunits of an enzyme
      essential in the biosynthesis of glycosylphosphatidylinositol (GPI). Since PIG-A
      is X-linked, mutational inactivation of the one single copy active in somatic
      cells entails absence from the cell surface of all the proteins that require GPI
      for attachment to the membrane: thus, mutant cells display a GPI-negative surface
      phenotype that can be easily detected by flow cytometry. The measurement of PIG-A
      mutants by counting cells with the GPI-negative phenotype has proved to be
      effective to measure mutant frequency in peripheral blood cells of humans and of
      others animals. Up to now, mu has been exceedingly difficult to measure in human
      cells; however, by using as a sentinel the PIG-A gene in lymphoblastoid cell
      lines we now have a test that makes it practical to measure mu in human cells.

PMID- 20034595
TI  - Thyroid hormone: an old drug to new indications.

PMID- 20034594
TI  - Formal representation of eligibility criteria: a literature review.
AB  - Standards-based, computable knowledge representations for eligibility criteria
      are increasingly needed to provide computer-based decision support for automated
      research participant screening, clinical evidence application, and clinical
      research knowledge management. We surveyed the literature and identified five
      aspects of eligibility criteria knowledge representation that contribute to the
      various research and clinical applications: the intended use of computable
      eligibility criteria, the classification of eligibility criteria, the expression
      language for representing eligibility rules, the encoding of eligibility
      concepts, and the modeling of patient data. We consider three of these aspects
      (expression language, codification of eligibility concepts, and patient data
      modeling) to be essential constructs of a formal knowledge representation for
      eligibility criteria. The requirements for each of the three knowledge constructs
      vary for different use cases, which therefore should inform the development and
      choice of the constructs toward cost-effective knowledge representation efforts.
      We discuss the implications of our findings for standardization efforts toward
      knowledge representation for sharable and computable eligibility criteria.

PMID- 20034596
TI  - Enhancement of immune responses to influenza vaccine (H3N2) by ginsenoside Re.
AB  - This study was designed to evaluate the adjuvant effect of ginsenoside Re
      isolated from the root of Panax ginseng on the immune responses elicited by split
      inactivated H3N2 influenza virus antigen in a mouse model. Forty-eight ICR mice
      were randomly distributed into six groups with 8 mice in each group. All animals
      were subcutaneously (s.c.) immunized twice on weeks 0 and 3 with 50 microg Re,
      inactivated H3N2 influenza virus antigen equivalent to 10 or 100 ng of
      hemogglutinin (HA) or inactivated H3N2 influenza virus antigen equivalent to 10
      ng HA adjuvanted with Re (25, 50 or 100 microg). Two weeks after the boost, blood
      samples were collected for measurement of serum IgG, the IgG isotypes and HI
      titers. Splenocytes were separated for the detection of lymphocyte proliferation
      and production of IFN-gamma and IL-5 in vitro. Results showed that co
      administration of Re significantly enhanced serum specific IgG, IgG1, IgG2a and
      IgG2b responses, HI titers, lymphocyte proliferation responses as well as IFN
      gamma and IL-5 secretions, indicating that both Th1 and Th2 were activated.
      Considering the adjuvant effect demonstrated in this study, Re deserve further
      studies for improving the quality of vaccines where mixed Th1/Th2 immune
      responses are needed.

PMID- 20034597
TI  - Isolation of mitochondria for biogenetical studies: An update.
AB  - The use of good quality preparations of isolated mitochondria is necessary when
      studying the mitochondrial biogenetical activities. This article explains a fast
      and simple method for the purification of mammalian mitochondria from different
      tissues and cultured cells, that is suitable for the analysis of many aspects of
      the organelle's biogenesis. The mitochondria isolated following the protocol
      described here, are highly active and capable of DNA, RNA and protein synthesis.
      Mitochondrial tRNA aminoacylation, mtDNA-protein interactions and specific import
      of added proteins into the organelles, can also be studied using this kind of
      preparations.

PMID- 20034598
TI  - Isolation of novel Pseudomonas syringae promoters and functional characterization
      in polyhydroxyalkanoate-producing pseudomonads.
AB  - A library of genomic DNA fragments of Pseudomonas syringae pv. tomato DC3000 was
      constructed in a lacZalpha-containing plasmid, pBS29. The library was used in a
      preliminary alpha-complementation-based screen to identify clones with promoter
      activity in Escherichia coli. Ten positive clones were sequenced and their
      locations in the chromosomal DNA of DC3000 strain were mapped. Five positive
      clones (P2, P3, P4, P6 and P8) were further assayed for promoter activity in
      three polyhydroxyalkanoate-producing pseudomonads: Pseudomonas resinovorans, P.
      corrugata and P. chlororaphis. To this end, a green-fluorescent-protein gene
      (gfp) was cloned downstream from the putative (DC3000) promoter in a shuttle
      plasmid. We found that only Pseudomonas transformants harboring the gfp
      containing plasmid driven by putative promoter P2 showed fluorescence, indicating
      that this promoter is functioning in the three tested pseudomonads. Results of an
      in silico analysis of the P2 sequence further support the assignment of P2 as a
      bona fide promoter by the localization of putative -10 and -35 promoter regions
      and a transcription-factor-binding site, rpoD17, in this sequence. We
      successfully applied promoter P2 to drive the expression in P. chlororaphis of a
      recombinant alpha-galactosidase gene of Streptomyces coelicolor, which should be
      useful for the utilization of oligosaccharides of soy molasses for the production
      of polyhydroxyalkanoate biopolymer or rhamnolipid biosurfactant.

PMID- 20034599
TI  - Contribution of the intra-specimen variations in tissue mineralization to PTH-
      and raloxifene-induced changes in stiffness of rat vertebrae.
AB  - The intra-specimen spatial variation in mineralization of bone tissue can be
      changed by drug treatments that alter bone remodeling. However, the contribution
      of such changes to the overall biomechanical effect of a treatment on bone
      strength is not known. To provide insight into this issue, we used a rat model to
      determine the effects of ovariectomy, parathyroid hormone, and raloxifene (vs.
      sham) on the contribution of spatial variations in mineralization to treatment
      induced changes in vertebral stiffness. Mineral density was measured from 6
      microm voxel-sized quantitative micro-CT scans. Whole-vertebral and trabecular
      stiffness values were estimated using finite element analysis of these micro-CT
      scans, first including all intra-specimen variations in mineral density in the
      model and then excluding such variations by using a specimen-specific average
      density throughout each specimen. As expected, we found appreciable effects of
      treatment on overall bone stiffness, the effect being greater for the trabecular
      compartment (up to 52% reduction vs. sham, p<0.0001) than the whole vertebra
      (p=0.055). Intra-specimen mean mineralization was not changed with treatment but
      the intra-specimen variation in mineralization was, although the effect was small
      (4%). Intra-specimen spatial variations in mineralization accounted for 10-12%
      and 5-6% of overall stiffness of the trabecular compartment and whole vertebral
      body, respectively. However, after accounting for all treatment effects on bone
      geometry and trabecular microstructure, any treatment effects due to changes in
      mineralization were negligible (<2%), although statistically detectable (p<0.02).
      We conclude that, despite a role in the general biomechanical behavior of bone,
      the spatial variations in tissue mineralization, as measured by quantitative
      micro-CT, did not appreciably contribute to ovariectomy-, PTH-, or raloxifene
      induced changes in stiffness of the whole bone or the trabecular compartment in
      these rat vertebrae.

PMID- 20034600
TI  - Sonic hedgehog: a link between inflammation, gastric atrophy, and acid
      suppression?

PMID- 20034601
TI  - Colonoscopy: an unusual complication.

PMID- 20034602
TI  - The development of clinical guidelines by the American Gastroenterological
      Association.

PMID- 20034603
TI  - The role of bile acids in gallstone-induced pancreatitis.

PMID- 20034604
TI  - IV or not IV? Just one of the antibiotic questions in Whipple's disease.

PMID- 20034605
TI  - Immunogenicity and safety in adults of one dose of influenza A H1N1v 2009 vaccine
      formulated with and without AS03A-adjuvant: preliminary report of an observer
      blind, randomised trial.
AB  - Governments and public health officials are preparing vaccination campaigns
      against the 2009 influenza A H1N1v pandemic strain. We evaluated two inactivated
      split-virion A/California/7/2009 H1N1v pandemic vaccines formulated with/without
      AS03(A), an oil-in-water emulsion adjuvant system containing tocopherol. This
      ongoing observer-blind study randomised 130 healthy adults aged 18-60 years to
      receive either AS03(A)-adjuvanted H1N1 vaccine containing 5.25 microg
      haemagglutinin (HA) (N=64) or non-adjuvanted H1N1 vaccine containing 21 microg HA
      (N=66) on Days 0 and 21. We performed a first analysis of reactogenicity and
      serum haemagglutination-inhibition (HI) antibody responses, 21 days after dose 1.
      Before vaccination, 12.5% in the AS03(A)-adjuvanted group and 13.1% in the non
      adjuvanted group had vaccine-homologous HI titres >or=1:40. Immune responses were
      robust; HI seroconversion rates were 98.2% and 95.1% and HI seroprotection rates
      were 98.2% and 98.4%, respectively in the AS03(A) and non-adjuvanted groups. The
      vaccines were well tolerated with similar adverse event profiles. Solicited
      injection site and general symptoms were reported more frequently for AS03(A)
      adjuvanted vaccine but these were transient and mainly mild to moderate in
      intensity. Based on accepted immunological surrogates, these preliminary data
      suggest that one dose of either AS03(A)-adjuvanted H1N1v vaccine at a reduced HA
      dose or non-adjuvanted H1N1v vaccine at a fourfold higher dose is sufficient to
      immunise healthy adults. The strong immune response is consistent with prevalent
      immunological priming but as this and the ability to mount immune response after
      vaccination may be modulated by age, further investigations in children and in
      the elderly as well as on the persistence of the immune response are warranted.

PMID- 20034606
TI  - Haemophilus influenzae type b disease in HIV-infected children: a review of the
      disease epidemiology and effectiveness of Hib conjugate vaccines.
AB  - The paper reviews the literature on the epidemiology of Hib disease and the
      effectiveness of Hib conjugate vaccine (HibCV) in HIV-infected children. The
      current three-dose primary Hib conjugate vaccine schedule in low-income settings
      has had a striking impact on the incidence of Hib disease. However, HIV-infected
      children have an almost 6-fold higher risk of Haemophilus influenzae type b (Hib)
      invasive disease than HIV-uninfected children and HibCV effectiveness is lower in
      this population. HIV-related HibCV failures are difficult to detect without well
      functioning surveillance systems and HIV testing of cases. Breakthrough Hib cases
      have been noted in vaccinated HIV-infected children in South Africa. A HibCV
      booster dose in addition to the three-dose primary schedule is routine in many,
      but not all, high-income countries. In order to determine whether a booster dose
      should be given to HIV-infected children in developing countries, well-designed
      studies need to be conducted to better determine the persistence of protective
      antibody concentrations, response to booster doses of vaccine as well as timing
      of and risk factors for vaccine failure in HIV-infected children both treated and
      naive to antiretroviral drug therapy (ART). Meanwhile, physicians and public
      health personnel should be especially vigilant at ensuring that HIV-infected
      infants receive their primary doses of HibCV, ART and co-trimoxazole prophylaxis.
      Until more definitive evidence is available, physicians may also need to consider
      a booster dose for such children irrespective of ART status. In any updating of
      vaccine schedules, HIV-infected children need particular consideration.

PMID- 20034608
TI  - Evaluation of a sudden brake warning system: effect on the response time of the
      following driver.
AB  - This study used a video-based braking simulation dual task to carry out a
      preliminary evaluation of the effect of a sudden brake warning system (SBWS) in a
      leading passenger vehicle on the response time of the following driver. The
      primary task required the participants (N=25, 16 females, full NZ license
      holders) to respond to sudden braking manoeuvres of a lead vehicle during day and
      night driving, wet and dry conditions and in rural and urban traffic, while
      concurrently performing a secondary tracking task using a computer mouse. The
      SBWS in the lead vehicle consisted of g-force controlled activation of the rear
      hazard lights (the rear indicators flashed), in addition to the standard brake
      lights. Overall, the results revealed that responses to the braking manoeuvres of
      the leading vehicles when the hazard lights were activated by the warning system
      were 0.34 s (19%) faster compared to the standard brake lights. The SBWS was
      particularly effective when the simulated braking scenario of the leading vehicle
      did not require an immediate and abrupt braking response. Given this, the SBWS
      may also be beneficial for allowing smoother deceleration, thus reducing fuel
      consumption. These preliminary findings justify a larger, more ecologically valid
      laboratory evaluation which may lead to a naturalistic study in order to test
      this new technology in 'real world' braking situations.

PMID- 20034607
TI  - Increased immunogenicity of HIV-1 p24 and gp120 following immunization with
      gp120/p24 fusion protein vaccine expressing alpha-gal epitopes.
AB  - Developing an effective HIV-1 vaccine will require strategies to enhance antigen
      presentation to the immune system. In a previous study we demonstrated a marked
      increase in immunogenicity of the highly glycosylated HIV-1 gp120 protein
      following enzymatic addition of alpha-gal epitopes to the carbohydrate chains. In
      the present study we determined whether gp120(alphagal) can also serve as an
      effective platform for targeting other HIV-1 proteins to APC and thus increase
      immunogenicity of both proteins. For this purpose we produced a recombinant
      fusion protein between gp120 and the HIV-1 matrix p24 protein (gp120/p24).
      Multiple alpha-gal epitopes were synthesized enzymatically on the gp120 portion
      of the fusion protein to generate a gp120(alphagal)/p24 vaccine. Immune responses
      to gp120(alphagal)/p24 compared to gp120/p24 vaccine lacking alpha-gal epitopes
      were evaluated in alpha1,3galactosyltransferase knockout (KO) mice. These mice
      lack alpha-gal epitopes and, therefore, are capable of producing the anti-Gal
      antibody. T cell responses to p24, as assessed by ELISPOT and by CD8+ T cells
      intracellular staining assays for IFNgamma, was on average 12- and 10-fold
      higher, respectively, in gp120(alphagal)/p24 immunized mice than in mice
      immunized with gp120/p24. In addition, cellular and humoral immune responses
      against gp120 were higher by 10-30-fold in mice immunized with
      gp120(alphagal)/p24 than in gp120/p24 immunized mice. Our data suggest that the
      alpha-gal epitopes on the gp120 portion of the fusion protein can significantly
      augment the immunogenicity of gp120, as well as that of the fused viral protein
      which lacks alpha-gal epitopes. This strategy of anti-Gal mediated targeting to
      APC may be used for production of effective HIV-1 vaccines comprised of various
      viral proteins fused to gp120.

PMID- 20034609
TI  - Age- and sex-related changes of mandibular condylar cartilage and subchondral
      bone: a histomorphometric and micro-CT study in rats.
AB  - OBJECTIVE: To quantify the age- and sex-related changes in the rat condylar
      cartilage and subchondral bone. METHODS: SD rats were obtained at the ages of 2,
      3, 4, 5, 6 and 7 months. For each sex, the temporomandibular joints tissue blocks
      from four rats were subjected to histological assessment of cartilage thickness
      and subchondral bone architecture; for the remaining three rats, the mandibular
      condyles were delivered for gross measurement and evaluation of the
      mineralization and architecture properties of the subchondral bone by means of
      micro-CT. RESULTS: Rapid decrease of cartilage thickness but increase of
      subchondral bone density occurred respectively from 2 to 3 and 3 to 4 months old
      in female and 2 to 4 and 3 to 5 months old in male (P<0.05), whereas rapid
      changes of subchondral bone architecture occurred from 3 to 4 months old in both
      sexes (P<0.05). The significant enlargement of condyle size occurred at 4 or 5
      months old in female but at 5 or 6 months in male (P<0.05). CONCLUSION: This
      study demonstrated that the rapid developmental changes of rat condylar cartilage
      and subchondral bone primarily occurred before 4 months of age, resulting in
      thinner cartilage but larger and thicker subchondral bone, and they were followed
      by rapid growth in condylar size. Sex differences were identified that the
      endochondral ossification of fibrocartilage and formation of subchondral bone
      were faster in female than in male rats, leading to the earlier enlargement of
      condyle in female than in male.

PMID- 20034610
TI  - Expression of Wnt5a in tooth germs and the related signal transduction analysis.
AB  - OBJECTIVE: Wnt5a is generally considered a non-canonical Wnt family member and
      plays an important role in the development of several tissues through regulation
      of cell fate, proliferation, migration, polarity and death. This study
      investigates its expression mode in human tooth development and the involved cell
      signal transduction pathways, as they remain unclear. DESIGN: The expression of
      Wnt5a was analyzed by immunohistochemistry method. Recombinant adenovirus
      encoding full-length Wnt5a cDNA was constructed to investigate four cell signal
      pathways and nine dentinogenesis nuclear transcription factors in response to
      Wnt5a in human dental papilla cells (HDPCs). RESULTS: Immunostaining revealed
      that Wnt5a was expressed in enamel epithelium cells from the bud stage, and in
      odontoblast layers and dental papilla tissues from early bell stage of human
      tooth development onward. Western blot analysis indicated that p42/44 MAPK, p38
      MAPK, JNK and AKT signal pathways could be phosphorylated by WNT5A. RT-PCR
      analysis showed that Wnt5a increased the expression of DLX1, DLX2, LEF1, MSX2,
      PAX9 and RUNX2 mRNA, but decreased BARX1 and PITX2 mRNA. CONCLUSIONS: It was
      concluded that WNT5A is expressed in human tooth development, and that p42/44
      MAPK, p38 MAPK, JNK and AKT signal pathways and DLX1, DLX2, LEF1, MSX2, PAX9,
      RUNX2 could be activated by Wnt5a.

PMID- 20034611
TI  - Adopting the perspective of another in belief attribution: contribution of
      Relational Frame Theory to the understanding of impairments in schizophrenia.
AB  - Impaired ability of identifying mental states is a characteristic of
      schizophrenia spectrum disorders. In particular, people suffering from this
      illness tend to fail at attributing a belief to another, which has been linked to
      difficulties in changing interpersonal perspective. Following the view of
      Relational Frame Theory on perspective-taking skills, the current study aimed at
      examining the involvement of social anhedonia, one of the frequent features of
      schizophrenia, in the development of deficits in reversing the I-YOU relation
      (i.e., adopting the perspective of another). A task consisting of attributing a
      belief to another or to the self was employed with 30 non-clinical participants
      with a high level of social anhedonia and with 15 patients diagnosed with
      schizophrenia. In comparison to two control groups, both experimental groups
      showed significant poorer performance when adopting the perspective of another.
      These results constitute important indications to target specific relational
      repertoires when attempting to remediate impairments in mental states attribution
      linked to schizophrenia.

PMID- 20034612
TI  - Learning and generalization in schizophrenia: effects of disease and
      antipsychotic drug treatment.
AB  - BACKGROUND: Schizophrenia involves alterations in hippocampal function. The
      implications of these alterations for memory function in the illness remain
      poorly understood. Furthermore, it remains unknown how memory is impacted by drug
      treatments for schizophrenia. The goal of this study was to delineate specific
      memory processes that are disrupted in schizophrenia and explore how they are
      affected by medication. We specifically focus on memory generalization--the
      ability to flexibly generalize memories in novel situations. METHODS: Individuals
      with schizophrenia (n = 56) and healthy control subjects (n = 20) were tested on
      a computerized memory generalization paradigm. Participants first engaged in
      trial-by-error associative learning. They were then asked to generalize what they
      learned by responding to novel stimulus combinations. Individuals with
      schizophrenia were tested on or off antipsychotic medication, using a between
      subject design in order to eliminate concerns about learning-set effects.
      RESULTS: Individuals with schizophrenia were selectively impaired in their
      ability to generalize knowledge, despite having intact learning and memory
      accuracy. This impairment was found only in individuals tested off medication.
      Individuals tested on medication generalized almost as well as healthy control
      subjects. This between-group difference was selective to memory generalization.
      CONCLUSIONS: These findings suggest that individuals with schizophrenia have a
      selective alteration in the ability to flexibly generalize past experience toward
      novel learning environments. This alteration is unaccompanied by global memory
      impairments. Additionally, the results indicate a robust generalization
      difference on the basis of medication status. These results suggest that
      hippocampal abnormalities in schizophrenia might be alleviated with antipsychotic
      medication, with important implications for understanding adaptive memory-guided
      behavior.

PMID- 20034613
TI  - The female urine sniffing test: a novel approach for assessing reward-seeking
      behavior in rodents.
AB  - BACKGROUND: Abnormal hedonic behavior is a key feature of many psychiatric
      disorders. Several paradigms measure reward-seeking behavior in rodents, but each
      has limitations. We describe a novel approach for monitoring reward-seeking
      behavior in rodents: sniffing of estrus female urine by male mice, along with
      number of ultrasonic vocalizations (USVs) emitted during the test. METHODS: The
      female urine sniffing test (FUST) was designed to monitor reward-seeking activity
      in rodents together with tests of helplessness and sweet solution preference.
      USVs and dopamine release from the nucleus accumbens (NAc) were recorded.
      Sniffing activity was measured in 1) manipulation-naive C57BL/6J and 129S1/SVImJ
      mice and Wistar-Kyoto rats; 2) stressed mice; 3) two groups of mice that
      underwent the learned helplessness paradigm-one untreated, and one treated with
      the SSRI citalopram; and 4) GluR6 knockout mice, known to display lithium
      responsive, mania-related behaviors. RESULTS: Males from all three strains spent
      significantly longer sniffing female urine than sniffing water. Males emitted
      USVs and showed significantly elevated NAc dopamine levels while sniffing urine.
      Foot-shock stress significantly reduced female urine sniffing time. Compared with
      mice that did not undergo the LH paradigm, LH males spent less time sniffing
      female urine, and citalopram treatment alleviated this reduction. Compared with
      their wildtype littermates, GluR6KO males sniffed female urine longer and showed
      enhanced saccharin preference. CONCLUSIONS: In rodents, sniffing female urine is
      a preferred activity accompanied by biological changes previously linked to
      reward-seeking activities. The FUST is sensitive to behavioral and genetic
      manipulation and to relevant drug treatment.

PMID- 20034614
TI  - Phospholipase A2 and cyclooxygenase 2 genes influence the risk of interferon
      alpha-induced depression by regulating polyunsaturated fatty acids levels.
AB  - BACKGROUND: Phospholipase A2 (PLA2) and cyclooxygenase 2 (COX2) are the two key
      enzymes in the metabolism of polyunsaturated fatty acids, which in turn play an
      important role in cytokine-induced depression and sickness behavior. METHODS:
      Patients with chronic hepatitis C viral infection (n = 132) were assessed to
      examine the effects of seven single nucleotide polymorphisms in COX2 and PLA2
      genes on the development of depression during interferon (IFN)-alpha treatment; a
      subsample (n = 63) was assessed for the erythrocyte levels of the three main
      polyunsaturated fatty acids, docosahexaenoic acid (DHA), eicosapentaenoic acid
      (EPA), and arachidonic acid. An independent "replication" sample of patients with
      major depression unrelated to cytokine treatment (n = 82) was also examined.
      RESULTS: Twenty-eight percent of participants developed INF-alpha-induced
      depression. Participants with the PLA2 BanI GG or the COX2 rs4648308 AG genotypes
      had a higher risk of IFN-alpha-induced depression (odds ratio = 3.1 and 3.5,
      respectively). The "at risk" PLA2 genotype was associated with lower EPA levels,
      and the "at risk" COX2 genotype was associated with lower DHA levels, during IFN
      alpha treatment. The PLA2 BanI GG polymorphism was also associated with more
      somatic symptoms of depression, both in patients with INF-alpha-induced
      depression and in the replication sample of patients with major depression.
      CONCLUSIONS: Genetic variations in the COX2 and PLA2 genes increase the risk of
      IFN-alpha-induced depression, possibly by affecting the levels of EPA and DHA.
      Moreover, PLA2 genotype is associated with somatic symptoms in depression. Our
      study confirms the role of inflammatory mechanisms in major depression.

PMID- 20034615
TI  - Diminished neural processing of aversive and rewarding stimuli during selective
      serotonin reuptake inhibitor treatment.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are popular
      medications for anxiety and depression, but their effectiveness, particularly in
      patients with prominent symptoms of loss of motivation and pleasure, has been
      questioned. There are few studies of the effect of SSRIs on neural reward
      mechanisms in humans. METHODS: We studied 45 healthy participants who were
      randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake
      inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group
      design. We used functional magnetic resonance imaging to measure the neural
      response to rewarding (sight and/or flavor of chocolate) and aversive stimuli
      (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final
      day of drug treatment. RESULTS: Citalopram reduced activation to the chocolate
      stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In
      contrast, reboxetine did not suppress ventral striatal activity and in fact
      increased neural responses within medial orbitofrontal cortex to reward.
      Citalopram also decreased neural responses to the aversive stimuli conditions in
      key "punishment" areas such as the lateral orbitofrontal cortex. Reboxetine
      produced a similar, although weaker effect. CONCLUSIONS: Our findings are the
      first to show that treatment with SSRIs can diminish the neural processing of
      both rewarding and aversive stimuli. The ability of SSRIs to decrease neural
      responses to reward might underlie the questioned efficacy of SSRIs in depressive
      conditions characterized by decreased motivation and anhedonia and could also
      account for the experience of emotional blunting described by some patients
      during SSRI treatment.

PMID- 20034616
TI  - Temporal reward discounting in attention-deficit/hyperactivity disorder: the
      contribution of symptom domains, reward magnitude, and session length.
AB  - BACKGROUND: Theoretical models have hypothesized that one core problem in
      attention-deficit/hyperactivity disorder (ADHD) is abnormal reward processing.
      Temporal reward discounting (decreases in subjective reward value due to
      prereward delay) is of interest because of its relation with a key symptom of
      ADHD-impulsivity. This study investigated 1) whether steep temporal reward
      discounting (TD) is associated with ADHD-combined type (ADHD-C)/symptoms of
      hyperactivity-impulsivity specifically; 2) the role of reward magnitude in TD in
      ADHD-C/participants with symptoms of hyperactivity-impulsivity; and 3) whether
      steep TD in ADHD-C/participants with symptoms of hyperactivity-impulsivity is
      affected by session length. METHODS: Three TD tasks were administered to children
      and adolescents (aged 6-17) with ADHD-C (n = 25), ADHD-inattentive type (ADHD-I;
      n = 20), and matched typically developing participants (n = 37). Reward magnitude
      and session length were varied. RESULTS: Steep TD was observed in participants
      with ADHD-C but not in those with ADHD-I, independent of reward magnitude and
      session length. Dimensional analyses revealed that steep TD was associated with
      hyperactivity-impulsivity (transcending the arbitrary cutoff for ADHD subtypes),
      especially when reward magnitude at the trial level was small. CONCLUSIONS: These
      findings suggest that steep TD in ADHD is best thought of as a correlate of the
      symptom dimension of hyperactivity/impulsivity. Additionally, steep TD in ADHD is
      the result of a trade-off between delay and reward magnitude, with all factors
      contributing to choice preferences. These findings may help refine the delay
      aversion theory of ADHD, and provide evidence for the notion that unique reward
      processing is one mechanism associated with symptoms of hyperactivity
      impulsivity.

PMID- 20034617
TI  - Lateral prefrontal cortex mediates the cognitive modification of attentional
      bias.
AB  - BACKGROUND: A tendency to orient attention toward threatening stimuli may be
      involved in the etiology of anxiety disorders. In keeping with this, both
      psychological and pharmacological treatments of anxiety reduce this negative
      attentional bias. It has been hypothesized, but not proved, that psychological
      interventions may alter the function of prefrontal regions supervising the
      allocation of attentional resources. METHODS: The current study examined the
      effects of a cognitive training regime on attention. Participants were randomly
      assigned to one of two training conditions: "attend-threat" training, which
      increases negative attentional bias, or "avoid-threat" training, which reduces
      it. The behavioral effects of training were assessed using a sample of 24 healthy
      participants. Functional magnetic resonance imaging data were collected in a
      further 29 healthy volunteers using a protocol that allowed the influence of both
      stimuli valence and attention to be discriminated. RESULTS: Cognitive training
      induced the expected attentional biases in healthy volunteers. Further, the
      training altered lateral frontal activation to emotional stimuli, with these
      areas responding specifically to violations of the behavioral rules learned
      during training. Connectivity analysis confirmed that the identified lateral
      frontal regions were influencing attention as indexed by activity in visual
      association cortex. CONCLUSIONS: Our results indicate that frontal control over
      the processing of emotional stimuli may be tuned by psychological interventions
      in a manner predicted to regulate levels of anxiety. This directly supports the
      proposal that psychological interventions may influence attention via an effect
      on the prefrontal cortex.

PMID- 20034619
TI  - Isolation, structure, and characterization of the putative soluble amyloses from
      potato, wheat, and rice starches.
AB  - Amylose, a putative linear alpha-(1-->4)-glucan and a component of most starches,
      was isolated from potato, rice, and wheat starches by forming the 1-butanol
      complex in a solution of the starches. It previously had been found that these
      amyloses were incompletely hydrolyzed by beta-amylase, indicating that it was
      partially branched. Solubilization of the butanol complex in water and steam
      distillation of the 1-butanol, followed by cooling to 4 degrees C gave
      precipitation of the double helical, linear, retrograded amylose over a 15 h
      period, leaving the soluble amylose in solution. The soluble amyloses were
      precipitated with two volumes of ethanol, and the precipitate was solubilized and
      reprecipitated to remove traces of linear amylose. The precipitated, soluble
      amyloses, were partially branched and had properties intermediate between linear
      amylose and amylopectin. The water solubility of the potato amylose was 10.52
      mg/mL, with a number-average degree of polymerization (DP(n)) of 8440 and 2.1%
      branch linkages that had a DP(n) of 48; the water solubility of the rice amylose
      was 8.83 mg/mL, with a DP(n) of 2911 and 1.4% branch linkages that had a DP(n) of
      72; and the water solubility of wheat amylose was 6.33 mg/mL, with a DP(n) of
      1160 and 1.6% branch linkages that had a DP(n) of 64. The three soluble amyloses
      have structures and properties intermediate between the nearly water insoluble
      (<or= 1mg/mL), linear amylose, and the highly water-soluble, 4-5% branched,
      amylopectin.

PMID- 20034620
TI  - Structural characterization of teichoic acids from Lactobacillus brevis.
AB  - Teichoic acids are a major constituent of the cell wall of Gram-positive
      bacteria. Structural characterization of lipoteichoic and teichoic acids isolated
      from Lactobacillus brevis was undertaken using 1D and 2D NMR experiments as well
      as chemical methodology. Compositional analysis indicated the presence of high
      amounts of glycerol, glucose, and alanine. In the case of LTA octadecenoic acid
      was also detected. The basic LTA/WTA structure was identified as 1,3
      poly(glycerol phosphate) nonstoichiometrically substituted at C-2 of the glycerol
      residues with D-Ala or alpha-D-Glc. In the case of LTA a higher amount of Ala
      could be detected and partial alanylation at position C-6 of the Glc could also
      be observed.

PMID- 20034618
TI  - Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent
      manner.
AB  - BACKGROUND: Ghrelin is a potent orexigenic hormone that likely impacts eating via
      several mechanisms. Here, we hypothesized that ghrelin can regulate extra
      homeostatic, hedonic aspects of eating behavior. METHODS: In the current study,
      we assessed the effects of different pharmacological, physiological, and genetic
      models of increased ghrelin and/or ghrelin-signaling blockade on two classic
      behavioral tests of reward behavior: conditioned place preference (CPP) and
      operant conditioning. RESULTS: Using both CPP and operant conditioning, we found
      that ghrelin enhanced the rewarding value of high-fat diet (HFD) when
      administered to ad lib-fed mice. Conversely, wild-type mice treated with ghrelin
      receptor antagonist and ghrelin receptor-null mice both failed to show CPP to HFD
      normally observed under calorie restriction. Interestingly, neither pharmacologic
      nor genetic blockade of ghrelin signaling inhibited the body weight homeostasis
      related, compensatory hyperphagia associated with chronic calorie restriction.
      Also, ghrelin's effects on HFD reward were blocked in orexin-deficient mice and
      wild-type mice treated with an orexin 1 receptor antagonist. CONCLUSIONS: Our
      results demonstrate an obligatory role for ghrelin in certain rewarding aspects
      of eating that is separate from eating associated with body weight homeostasis
      and that requires the presence of intact orexin signaling.

PMID- 20034621
TI  - Glycosylation of lysine-containing pentapeptides by glucuronic acid: new insights
      into the Maillard reaction.
AB  - The formation of glycosylation products in model systems consisting of d
      glucuronic acid (GlcA) and lysine-containing peptides, such as Lys-Gly-Gly-Phe
      Leu (1), Gly-Lys-Gly-Phe-Leu (4) and Ac-Gly-Lys-Gly-Phe-Leu (6), was examined to
      evaluate the site specificity as well as the extent and nature of the
      modification. Peptides were reacted with GlcA either in solution or under dry
      heating conditions. From the incubations performed in solution (MeOH), the
      corresponding (1-deoxy-D-fructofuranos-1-yluronic acid)-peptide derivatives
      (Amadori compounds) were isolated. Whereas reaction of 1 resulted in the
      formation of mono-glycosylated Amadori compound 2 with the sugar moiety attached
      to the N(epsilon)-amino group of the Lys residue and its di-glycosylated analogue
      3, exposure of 4 to GlcA afforded only di-glycosylated peptide 5. From the
      incubation of GlcA with Ac-Gly-Lys-Gly-Phe-Leu (6) performed under mild dry
      heating conditions (50 degrees C) in an environment of 75% relative humidity,
      besides Amadori compound 7, two new Maillard reaction products were isolated that
      contained 3-hydroxypyridinium (8) and 3-hydroxy-picolinic acid moiety (9). The
      mechanism for the formation of pyridinium products is discussed.

PMID- 20034623
TI  - [Empiric anti-infective agents of intra-abdominal infection].

PMID- 20034624
TI  - Does verb bias modulate syntactic priming?
AB  - In a corpus analysis of spontaneous speech Jaeger and Snider (2007) found that
      the strength of structural priming is correlated with verb alternation bias. This
      finding is consistent with an implicit learning account of syntactic priming:
      because the implicit learning model implemented by Chang (2002), Chang, Dell, and
      Bock (2006), and Chang, Dell, Bock, and Griffin (2000) uses probabilistic
      information about different verb-structure combinations to predict the form of
      sentences, it predicts that primes exert stronger priming when they are less
      expected, given the syntactic preference of their main verb. We tested this claim
      experimentally by comparing the strength of double-object dative priming (DO) and
      prepositional object dative priming (PO) between dative verbs with differing
      syntactic preferences in a syntactic priming experiment. The syntactic
      preferences of the prime and target verbs were first measured in a picture
      description experiment. Consistent with an implicit learning account, the results
      showed a verb-specific effect of inverse preference: the strength of DO-priming
      was modulated by the alternation bias of the dative verbs that were used in the
      primes.

PMID- 20034622
TI  - Single-step bioconversion for the preparation of L-gulose and L-galactose.
AB  - Both carbohydrate monomers L-gulose and L-galactose are rarely found in nature,
      but are of great importance in pharmacy R&D and manufacturing. A method for the
      production of L-gulose and L-galactose is described that utilizes recombinant
      Escherichia coli harboring a unique mannitol dehydrogenase. The recombinant E.
      coli system was optimized by genetic manipulation and directed evolution of the
      recombinant protein to improve conversion. The resulting production process
      requires a single step, represents the first readily scalable system for the
      production of these sugars, is environmentally friendly, and utilizes inexpensive
      reagents, while producing L-galactose at 4.6 g L(-1)d(-1) and L-gulose at 0.90 g
      L(-1)d(-1).

PMID- 20034625
TI  - Biomarkers of PAHs exposure in crabs Ucides cordatus: laboratory assay and field
      study.
AB  - Pyrene metabolites in urine and micronucleus in haemocytes of crabs (Ucides
      cordatus) were tested as biomarkers of exposure to oil derived PAHs in mangrove
      sediments. The goal was to verify how well pyrene metabolites in urine represent
      levels of oil contamination in mangroves and whether the micronuclei assay
      indicates exposure. For this, bioassays were performed using crabs from clean and
      contaminated areas, and field studies were conducted in four mangroves. Results
      of the bioassay show that U. cordatus assimilates, metabolises, and excretes
      pyrene in urine as pyrene-1-glucoside, pyrene-sulphate and pyrene-conjugate. OH
      pyrene-sulphate was the major metabolite produced/excreted over 120 h of
      observation by crabs from the clean mangrove. The production/excretion of pyrene
      1-glucoside in this case increased linearly with time at a rate of 2.3 x 10(
      10)mol L(-1)day(-1). The number of micronuclei in haemocytes also increased with
      the time after pyrene inoculation, indicating that exposure to pyrene triggers
      genotoxic and mutagenic response. In crabs from a heavily oil-contaminated
      mangrove pyrene-1-glucoside was the major metabolite, an indication that
      production/excretion of a certain metabolite varies depending on adaptation of
      the animal to the environment. A highly significant correlation was found between
      the concentration of pyrene metabolites in urine of field crabs expressed as OH
      pyrene equivalents and the sum of 38 PAHs determined in hepatopancreas/sediments
      (r=0.825, n=23, p<0.05). The response of these crabs to the micronuclei assay was
      not significantly related to concentration of individual or total PAHs.
      Nevertheless, metabolite results prove U. cordatus as excellent bioindicator for
      evaluating environmental quality in mangrove areas as related to PAHs and oil
      contamination.

PMID- 20034626
TI  - Preimplantation genetic diagnosis (PGD) improves pregnancy outcome for
      translocation carriers with a history of recurrent losses.
AB  - OBJECTIVE: To determine if preimplantation genetic diagnosis (PGD) for
      translocation carriers with three or more pregnancy losses reduces loss rates.
      DESIGN: Retrospective review of data. SETTING: Preimplantation genetic diagnosis
      laboratory servicing IVF groups. PATIENT(S): Patients (n = 192) undergoing PGD
      for either a reciprocal translocation or Robertsonian translocation who had three
      or more previous pregnancy losses. INTERVENTION(S): Preimplantation genetic
      diagnosis for translocations. MAIN OUTCOME MEASURE(S): Pregnancy loss rate,
      pregnancy success rate defined as delivery of at least one child or an ongoing
      pregnancy in the third trimester, and length of time to success. RESULT(S):
      Pregnancy loss rate was significantly reduced to 13% post-PGD compared with 88.5%
      in previous non-PGD pregnancies and to 35% to 64% from naturally conceived
      pregnancies as reported in the literature. Pregnancy success rate was 87%.
      Conception occurred after an average of 1.4 cycles or <4 months. CONCLUSION(S):
      Individuals with translocations who have experienced three or more losses benefit
      from PGD by realizing a significant reduction in loss rate and improvement in
      rate of success of pregnancy. Length of time to conceive is also dramatically
      reduced compared with data in the literature for similar populations not
      undergoing PGD.

PMID- 20034627
TI  - Use of intrauterine devices in women with uterine anatomic abnormalities.
AB  - OBJECTIVE: To examine the evidence regarding the safety and effectiveness of
      intrauterine devices (IUDs) in women with uterine abnormalities. METHODS: We
      searched PubMed for all peer-reviewed articles in any language that had been
      published on the topic from database inception to September 2009. Primary
      research articles were included if they addressed the safety or effectiveness of
      any type of IUD among women with Mullerian anomalies or uterine synechiae.
      RESULTS: In total, 19 case reports or case series met the inclusion criteria.
      Reported complications included expulsion, pregnancy, bleeding, perforation, and
      pain. In several case reports, no complications were reported. CONCLUSION:
      Evidence concerning the safety and effectiveness of IUD use among women with
      uterine abnormalities is very limited.

PMID- 20034628
TI  - Expanding uterotonic protection following childbirth through community-based
      distribution of misoprostol: operations research study in Nepal.
AB  - OBJECTIVE: To determine feasibility of community-based distribution of
      misoprostol for preventing postpartum hemorrhage (PPH) to pregnant woman through
      community volunteers working under government health services. METHODS:
      Implemented in one district in Nepal. The primary measure of performance was
      uterotonic protection after childbirth, measured using pre- and postintervention
      surveys (28 clusters, each with 30 households). Maternal deaths were ascertained
      through systematic health facility and community-based surveillance; causes of
      death were assigned based on verbal autopsy. RESULTS: Of 840 postintervention
      survey respondents, 73.2% received misoprostol. The standardized proportion of
      vaginal deliveries protected by a uterotonic rose from 11.6% to 74.2%. Those
      experiencing the largest gains were the poor, the illiterate, and those living in
      remote areas. CONCLUSION: Community-based distribution of misoprostol for PPH
      prevention can be successfully implemented under government health services in a
      low-resource, geographically challenging setting, resulting in much increased
      population-level protection against PPH, with particularly large gains among the
      disadvantaged.

PMID- 20034629
TI  - Effects of zinc on plasma lipoprotein cholesterol concentrations in humans: a
      meta-analysis of randomised controlled trials.
AB  - BACKGROUND: Studies in humans and animals suggest that zinc has the potential to
      affect lipoprotein metabolism and hence impact cardiovascular disease risk.
      METHODS: A meta-analysis of controlled clinical trials was conducted to determine
      the effect of zinc supplementation on plasma cholesterol and triglyceride
      concentrations in humans. Potentially relevant studies were identified from a
      literature search covering the period 1980-2008 (inclusive), and additional
      citation searches. RESULTS: Thirty three interventions (n=14,238 subjects) were
      included in the random effects meta-analysis. No overall significant effects of
      zinc supplementation were observed for plasma cholesterol, low-density
      lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol or
      plasma triglyceride concentrations. Plasma zinc concentrations increased
      significantly (+2.42+/-0.25 micromol/L, P<0.001; n=14,047). Secondary analyses in
      individuals classified as healthy revealed that zinc supplementation is
      associated with a significant decrease in plasma HDL cholesterol concentrations (
      0.10+/-0.02 mmol/L, P<0.001; n=13,215), equivalent to a 7% decrease from
      baseline. CONCLUSION: No effect of zinc supplementation on plasma lipoproteins
      was detected in the overall analysis. In individuals classified as healthy, zinc
      supplementation is associated with a decrease in HDL cholesterol concentrations
      and thus contributes to an increased risk of coronary heart disease.

PMID- 20034630
TI  - Determination of the carboxylic acids in acidic and basic process samples by
      capillary zone electrophoresis.
AB  - Capillary zone electrophoresis (CZE) with indirect UV detection was used in
      developing a method for the simultaneous determination of inorganic anions,
      aliphatic and heterocyclic organic acids in various processed samples. The
      analytes were determined simultaneously in 10 min using an electrolyte containing
      20mM 2,3-pyrazine dicarboxylic acid, 65mM tricine, 2mM BaCl(2), 0.5mM
      cetyltrimethylammonium bromide, and 2M urea at pH 8.06. Linear plots for the
      analytes were obtained in the concentration range of 2-150 mg L(-1). Relative
      standard deviations (RSDs) of peak areas during a 3-day analysis period varied
      from 5.5% for glycolate to 9.5% for oxalate. RSDs of migration times varied
      between 0.4% and 1.1%. The detection limit (at S/N 3) was 1 mg L(-1) for all the
      analytes studied. The proposed method was successfully demonstrated for the
      determination of carboxylic acids in eight oxygen treated samples of commercial
      softwood and hardwood kraft lignin and two red wine samples of Pinot Noir grapes.
      In the kraft lignin samples the concentrations of carboxylic acids correspond to
      the oxidation time. The acid concentrations of wine varied considerable.

PMID- 20034631
TI  - In-line coupling headspace liquid-phase microextraction with capillary
      electrophoresis.
AB  - An analytical technique of in-line coupling headspace liquid-phase
      microextraction (HS-LPME) with capillary electrophoresis (CE) was proposed to
      determine volatile analytes. A special cover unit of the sample vial was adopted
      in the coupling method. To evaluate the proposed method, phenols were used as
      model analytes. The parameters affecting the extraction efficiency were
      investigated, including the configuration of acceptor phase, kind and
      concentration of acceptor solution, extraction temperature and time, salt-out
      effect, sample volume, etc. The optimal enrichment factors of HS-LPME were
      obtained with the sample volume of about half of sample vials, which were
      confirmed by both the theoretical prediction and experimental results. The
      enrichment factors were obtained from 520 to 1270. The limits of detection (LODs,
      S/N=3) were in the range from 0.5 to 1 ng/mL each phenol. The recoveries were
      from 87.2% to 92.7% and the relative standard deviations (RSDs) were lower than
      5.7% (n=6). The proposed method was successfully applied to the quantitative
      analysis of the phenols in tap water, and proved to be a simple, convenient and
      reliable sample preconcentration and determination method for volatile analytes
      in water samples.

PMID- 20034632
TI  - Ultra trace analysis of 17 organochlorine pesticides in water samples from the
      Arctic based on the combination of solid-phase extraction and headspace solid
      phase microextraction-gas chromatography-electron-capture detector.
AB  - Solid-phase extraction (SPE) was combined with headspace solid-phase
      microextraction (HS-SPME) for the highly effective enrichment of 17 ultra trace
      organochlorine pesticides in water samples. The target compounds were
      successfully transferred from water samples to a gas chromatography capillary
      column by means of four consecutive steps, namely SPE, solvent conversion, HS
      SPME, and thermal desorption of the SPME fiber. Parameters, including elution
      volume and breakthrough volume in the SPE step, temperature in the solvent
      conversion step, and fiber type, ionic strength, extraction temperature,
      extraction time, and pH in the SPME step were optimized to improve the
      performance of the method through either single factor comparative experiment or
      the orthogonal experimental design approach. After optimization, the method gave
      high sensitivity with a method detection limit ranging from 0.0018 to 0.027 ng L(
      1), good repeatability with a relative standard deviation less than 20% (n=4) and
      acceptable recovery with a value mostly exceeding 60%. External standard
      calibration was employed for the quantification, and a wide linear range (from
      0.0010 to 60 ng mL(-1)) with R(2) values ranging from 0.9988 to 0.9999 were
      observed. In the end, the method was successfully applied to the Arctic samples,
      and the results showed that, among all the organochlorine pesticides,
      hexachlorocyclohexanes (HCHs) were the most predominant in the Arctic surface
      water body with sum of their concentrations ranging from 0.262 to 3.156 ng L(-1).

PMID- 20034633
TI  - Inhomogeneities in sodium decylsulfate doped 1,2-dipalmitoylphosphatidylcholine
      bilayer.
AB  - Differential scanning calorimetry (DSC), dynamic light scattering (DLS), and
      turbidity measurements have been used to study the effect of sodium decylsulfate,
      C10OS, on 1,2-dipalmitoylphosphatidylcholine, DPPC, vesicles. DSC measurements,
      performed soon after addition of C10OS solutions to DPPC vesicular dispersion, at
      several C10OS/DPPC molar ratios, showed the contemporary presence of maxima
      ascribable both to transitions of an unmodified DPPC membrane and to transitions
      related to membrane domains in which C10OS is also present. In all the considered
      samples only unilamellar vesicles are present as shown by DLS measurements
      carried out on aqueous DPPC and C10OS-DPPC systems. Also the aging of the samples
      confirmed the presence of SUV in the time scale of DSC measurements. On the basis
      of DSC results the pseudo-phase diagram of the system was drawn. This diagram
      does not represent a system in equilibrium, from a thermodynamic point of view,
      but only kinetically probable states. In fact the prolonged aging of the
      solutions used both for DSC and DLS scans highlight the disappearance of the
      unmodified DPPC membrane and its conversion into a mixed membrane. Turbidity
      measurements at 25 degrees C, performed as a function of surfactant composition,
      showed that C10OS initially contributes to increase the vesicles dimensions and
      allowed to calculate the saturation ratio C10OS/DPPC in the membrane. In
      contrast, at 45 degrees C the presence of surfactant gives origin immediately to
      smaller structures in comparison to vesicles, probably gel-state micelles.

PMID- 20034634
TI  - Polysynovitis after oligofructose overload in dairy cattle.
AB  - Acute bovine laminitis is a systemic disease with local manifestations primarily
      affecting the claws. However, distension of the tarsocrural joints has been
      observed after experimental oligofructose overload in dairy heifers as a part of
      the complex interpreted as acute, clinical laminitis. Therefore, the aim of the
      present study was to study bovine synovial joints and tendon sheaths after
      oligofructose overload. Ten dairy heifers received oral oligofructose overload
      (17 g/kg body weight); four were killed 24h after overload and six after 72 h.
      Six control heifers received tap water and were killed after 72 or 96 h. Clinical
      examination included locomotion scoring and palpation of the tarsocrural joints.
      Ruminal fluid and blood was collected for measurements of pH and hydration
      status. Total protein concentrations and white blood cell (WBC) counts were
      determined in synovial fluid collected from tarsocrural joints after death.
      Synovial joints and tendon sheaths were examined and synovial membranes were
      studied microscopically. Swabs taken from the synovial cavities were subject to
      bacteriological culture. Heifers with oligofructose overload developed signs of
      ruminal and systemic acidosis. Lameness was observed in three of ten heifers 24h
      after overload and in all remaining heifers after 72 h. Distension of tarsocrural
      joints was observed from 18 h after overload and peaked at 30 h when all examined
      joints were moderately or severely distended. The synovial fluid was turbid and
      protein content and WBC counts were increased at both 24 and 72 h compared with
      controls. Bacterial culture was negative. Synovial membranes 24 and 72 h after
      overload had a fibrinous and neutrophil inflammatory reaction that regressed in
      severity between 24 and 72 h after overload. Heifers subjected to oligofructose
      overload therefore developed generalized sterile neutrophilic polysynovitis.
      Focus on this aspect of bovine laminitis may shed new light on the pathogenesis
      of this complex disease.

PMID- 20034635
TI  - Assessment of atrial electromechanical delay by tissue Doppler echocardiography
      in patients with nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Atrial electromechanical delay (AEMD) calculated from tissue Doppler
      imaging (TDI) echocardiography can be an alternative to invasive
      electrophysiologic studies. We investigated whether the AEMD obtained from TDI is
      prolonged in patients with nonischemic dilated cardiomyopathy (DCM). METHODS:
      Fifty-five patients with nonischemic DCM (23 men/32 women; age, 43.9 +/- 14.8
      years) and 55 controls (20 men/35 women; age, 41.3 +/- 13.4 years) were included
      in this study. Atrial electromechanical delay (the time interval from the onset
      of P wave on electrocardiogram to the beginning of late diastolic wave [Am wave]
      on TDI) was calculated from the lateral and septal mitral annulus, and lateral
      tricuspid annulus (PA lateral, PA septum, and PA tricuspid, respectively). P-wave
      dispersion was calculated from the 12-lead electrocardiogram. RESULTS: PA lateral
      and PA septum duration were significantly longer in patients with nonischemic DCM
      than the controls (78.4 +/- 19.7 versus 53.8 +/- 6.6 and 55.2 +/- 16.3 versus
      40.5 +/- 6.2, P < .0001 for both; respectively). However, PA tricuspid duration
      was statistically similar between the 2 groups (36.4 +/- 10.9 versus 37.2 +/-
      5.7, P > or = .05). P-wave dispersion was significantly higher in nonischemic DCM
      patients than the controls (53.0 +/- 14.4 versus 37.5 +/- 5.5, P < .0001). PA
      lateral was correlated with the left atrial maximal volume (r = 0.64, P < .0001),
      P-wave dispersion (r = 0.65, P < .0001), and log B-type natriuretic peptide (NT
      proBNP) (r = 0.63, P < .0001). There was a statistically significant and negative
      correlation between the PA lateral and left ventricular ejection fraction (r = 
      0.63, P < .0001) and E-wave deceleration time (r = -0.34, P < .0001).
      Multivariate analysis revealed that left atrial maximal volume and log NT proBNP
      were the independent predictors of PA lateral (P < .0001 and P = .003,
      respectively). CONCLUSION: The AEMD was significantly prolonged in patients with
      nonischemic DCM. Left atrial enlargement and log NT proBNP were the independent
      predictors of this prolongation.

PMID- 20034636
TI  - A porcine model to study ex vivo reconditioning of injured donor lungs.
AB  - BACKGROUND: Brain death rapidly results in lung injury making many cadaveric
      donors unsuitable for lung transplantation. The aim of this study was to develop
      a porcine model of lung injury as a first step to study mechanisms to ameliorate
      the pretransplant graft quality during ex vivo perfusion. MATERIALS AND METHODS:
      Male pigs (47 +/- 8 kg) were divided into three groups: LPS-group [LPS] (n = 6)
      [instillation of lipopolysaccharides (15 mg/lung)]; saline-group [SAL] (n = 5)
      (50 mL saline/lung); and sham-group [SHAM] (n = 5). CT scans of the lungs were
      taken 17h before (T-17) and 31h after (T31) instillation. Broncho-alveolar lavage
      (BAL) was performed, and blood gases, hemodynamic, and aerodynamic parameters
      were measured at T 0 and T 50. Blood samples and temperature were taken at all
      time points. Pigs were sacrificed during cold pulmoplegia (T 50), and tissue
      samples were collected for histology. Wet lung weight was measured. RESULTS: Wet
      lung weight/body weight was higher in [LPS] versus [SAL] (P < 0.05). Total BAL
      cells were higher in [LPS] versus [SAL] and [SHAM] at T 50 (left: P < 0.001 and P
      < 0.01; right: P < 0.01 and P < 0.001). More neutrophils were present in BAL of
      [LPS] at T 50 versus T 0 (left: P < 0.001; right: P < 0.01). [LPS] demonstrated
      more ground glass opacities (GGO) on CT at T 31 compared with [SAL] and [SHAM] (P
      < 0.05). Histologically, more interstitial hemorrhage was observed in [LPS]
      versus [SAL] and [SHAM](P < 0.01). Neutrophils in blood increased and lymphocytes
      decreased in [LPS] versus [SAL] (P < 0.05). No differences were observed in
      hemodynamic and aerodynamic parameters and in saturation between groups at T 50.
      CONCLUSIONS: LPS instillation caused inflammation with more cells in BAL, changes
      on CT, and histology. However, no physiologic changes occurred.

PMID- 20034637
TI  - Extrathymic malignancies in thymoma patients with and without myasthenia gravis.
AB  - OBJECTIVE: The influence of myasthenia gravis (MG) on risk of cancer is
      uncertain. Using nationwide, comprehensive data, we investigated the association
      between MG and occurrence of extrathymic malignancies in thymoma patients, and
      also assessed the risk of consecutive extrathymic malignancies after thymoma
      diagnosis. METHODS: Two hundred twelve thymoma patients were identified at the
      Cancer Registry of Norway between 1969 and 2005. Records on all extrathymic
      malignancies for these patients were supplied from the Registry's database.
      Comparisons were made between MG and non-MG patients and between thymoma patients
      and the general population. RESULTS: The frequency of extrathymic malignancies
      was similar in MG and non-MG thymoma patients, and so was the survival after
      thymoma diagnosis. Extrathymic malignancies occurred in 10% of thymoma patients
      within 10 years following the thymoma diagnosis. Thymoma patients had a
      significantly increased risk of developing an extrathymic malignancy compared to
      the general population. This was not linked to any specific kind of cancer.
      Thymoma morphology was not a significant predictor for an increased risk of
      consecutive cancer. CONCLUSIONS: The immunological process underlying MG does not
      influence the risk of cancer in thymoma patients. Thymoma patients have a
      significantly increased risk of extrathymic malignancies. This is an intrinsic
      effect, being unaffected by a coexisting autoimmune disease such as MG and not
      specific for any type of cancer. Screening for extrathymic malignancies in
      thymoma patients is probably not recommendable, but clinicians should be aware of
      the high rate of extrathymic malignancies occurring in thymoma patients.

PMID- 20034638
TI  - Re: DNA microarray expression profiling of bladder cancer allows identification
      of noninvasive diagnostic markers L. Mengual, M. Burset, E. Ars, J. J. Lozano, H.
      Villavicencio, M. J. Ribal And A. Alcaraz J Urol 2009; 182: 741-748.

PMID- 20034639
TI  - Visualization and tissue distribution of alpha1L-adrenoceptor in human prostate
      by the fluorescently labeled ligand Alexa-488-silodosin.
AB  - PURPOSE: Although alpha(1L)-adrenoceptor is recognized as a target of alpha(1)
      antagonist therapy for benign prostatic hyperplasia, the most common techniques,
      such as immunohistochemistry and in situ hybridization, are not applicable to
      examine alpha(1L)-AR vs alpha(1A)-AR tissue distribution because alpha(1L)-AR is
      now considered another phenotype sharing the alpha(1A)-AR gene and protein
      molecule. We labeled the alpha(1A) and alpha(1L)-adrenoceptor selective
      antagonist silodosin (Kissei Pharmaceutical, Matsumoto, Japan) with the
      fluorophore Alexa Fluor(R) 488 (Alexa-488-silodosin) to visualize alpha(1L)-AR
      expression. MATERIALS AND METHODS: Radioligand binding and functional bioassay
      experiments were done to assess alpha(1)-AR expression in Chinese hamster ovary
      cells and human prostate tissues. Confocal imaging was subsequently performed.
      RESULTS: Although Alexa-488-silodosin had about 10 times lower affinity for all
      alpha(1)-AR subtypes than silodosin in binding and functional studies, it had
      high selectivity to alpha(1A) and alpha(1L)-ARs. Confocal imaging revealed clear
      localization of fluorescence on the membrane of Chinese hamster ovary cells
      expressing alpha(1A)-AR but not alpha(1B)-and alpha(1D)-ARs, and in the muscle
      layer of the human prostate. The fluorescent signal in Chinese hamster ovary
      cells disappeared in the presence of 3 nM prazosin but fluorescence was observed
      in the human prostate even in the presence of 100 nM prazosin. CONCLUSIONS: Alexa
      488-silodosin is a powerful fluorescent probe with high selectivity to alpha(1A)
      and alpha(1L)-ARs. Thus, Alexa-488-silodosin successfully visualizes the site of
      alpha(1L)-ARs in the muscle layer of the human prostate without losing its
      distinct pharmacological profile.

PMID- 20034641
TI  - Land-based nutrient enrichment of the Buccoo Reef Complex and fringing coral
      reefs of Tobago, West Indies.
AB  - Tobago's fringing coral reefs (FR) and Buccoo Reef Complex (BRC) can be affected
      locally by wastewater and stormwater, and regionally by the Orinoco River. In
      2001, seasonal effects of these inputs on water-column nutrients and
      phytoplankton (Chl a), macroalgal C:N:P and delta(15)N values, and biocover at FR
      and BRC sites were examined. Dissolved inorganic nitrogen (DIN, particularly
      ammonium) increased and soluble reactive phosphorus (SRP) decreased from the dry
      to wet season. Wet season satellite and Chl a data showed that Orinoco runoff
      reaching Tobago contained chromophoric dissolved organic matter (CDOM) but little
      Chl a, suggesting minimal riverine nutrient transport to Tobago. C:N ratios were
      lower (16 vs. 21) and macroalgal delta(15)N values higher (6.6 per thousand vs.
      5.5 per thousand) in the BRC vs. FR, indicating relatively more wastewater N in
      the BRC. High macroalgae and low coral cover in the BRC further indicated that
      better wastewater treatment could improve the health of Tobago's coral reefs.

PMID- 20034642
TI  - Fatty acid profiles of benthic environment associated with artificial reefs in
      subtropical Hong Kong.
AB  - Artificial reefs can enhance habitat heterogeneity, especially in seabed degraded
      by bottom-dredging and trawling. However, the trophodynamics of such reef systems
      are not well understood. This study provided baseline data on trophic
      relationships in the benthic environment associated with artificial reefs in late
      spring and mid summer of subtropical Hong Kong, using fatty acid profiles as an
      indicator. Data from sediments collected at the reef base, materials from
      sediment traps deployed on top and bottom of the reefs, total particulate matter
      from the water column and oyster tissues from reef surface were subjected to
      principal component analysis. Results showed variations of fatty acid profiles in
      the total particulate matter, upper sediment trap and oyster tissue samples
      collected in the two samplings, indicating seasonal, trophodynamic changes within
      the reef system. The wastes produced by fish aggregating at the reefs can also
      contribute a source of biodeposits to the nearby benthic environment.

PMID- 20034643
TI  - Influenza pandemic preparedness and severity assessment of pandemic (H1N1) 2009
      in South-east Asia.
AB  - Pandemic (H1N1) 2009 poses a serious global health threat. However, the global
      impact of this new pandemic remains uncertain. Past pandemics had different
      impacts on mortality which varied between countries. Several countries in South
      east Asia have already developed their national pandemic preparedness plans.
      However, these plans have focused on surveillance for and response to the highly
      pathogenic avian influenza (H5N1), including the rapid containment of H5N1. The
      newly emerged pandemic (H1N1) 2009 is different from H5N1 in terms of severity
      and requires different approaches. There are several factors that can potentially
      affect the severity of pandemic (H1N1) 2009, including a population's
      vulnerability and response capacity. The pattern of severity appears to be
      changing with the spread of pandemic (H1N1) 2009, which can be conceptualized in
      a step-wise manner based on observation of the current situation. The overall
      impact of pandemic (H1N1) 2009 remains unknown and it is difficult to assess its
      severity. However, there is an urgent need to assess its potential severity based
      on the available data so that appropriate responses can be provided in order to
      mitigate its impact.

PMID- 20034644
TI  - Getting back to basics during a public health emergency: a framework to prepare
      and respond to infectious disease public health emergencies.
AB  - This paper describes a simple framework developed by the World Health
      Organization, used to convey the concept of comprehensive and integrated public
      health response structures and to identify core public health capacity
      development needs. The framework highlights five core components of a response:
      surveillance, healthcare response, public health intervention, communication and
      command. This paper notes that to mount an effective public health response, each
      component requires sufficient capacity to meet demand, and effective
      relationships and mechanisms need to be established between components that
      support coordination, communication and collaboration.

PMID- 20034646
TI  - The non-pathogenic Australian lagovirus RCV-A1 causes a prolonged infection and
      elicits partial cross-protection to rabbit haemorrhagic disease virus.
AB  - Two caliciviruses occur in Australian wild rabbits: rabbit calicivirus Australia
      1 (RCV-A1) and rabbit haemorrhagic disease virus (RHDV), which is used in
      Australia as a biocontrol agent to reduce feral rabbit populations. There is
      concern that RCV-A1 acts as a natural vaccine and protects from lethal RHDV
      infection. To investigate this hypothesis, domestic rabbits were perorally
      infected with RCV-A1, monitored for 28 days and subsequently challenged with
      RHDV. We show that RCV-A1 causes a non-pathogenic infection and is shed in faeces
      for up to 7 days post-infection. RCV-A1 was detected in the bile 2 months post
      inoculation, indicating a prolonged or possible persistent infection. All animals
      infected with RCV-A1 developed antibodies cross-reacting to RHDV. When challenged
      with RDHV, half of the rabbits (n=4) survived the infection. The results indicate
      that RCV-A1 is likely to persist in rabbit populations and can elicit partial
      cross-protection to lethal RHDV infection.

PMID- 20034645
TI  - Regulatory function of cytomegalovirus-specific CD4+CD27-CD28- T cells.
AB  - CMV infection is characterized by high of frequencies of CD27-CD28- T cells. Here
      we demonstrate that CMV-specific CD4+CD27-CD28- cells are regulatory T cells
      (TR). CD4+CD27-CD28- cells sorted from CMV-stimulated PBMC of CMV-seropositive
      donors inhibited de novo CMV-specific proliferation of autologous PBMC in a dose
      dependent fashion. Compared with the entire CMV-stimulated CD4+ T-cell
      population, higher proportions of CD4+CD27-CD28- TR expressed FoxP3, TGFbeta,
      granzyme B, perforin, GITR and PD-1, lower proportions expressed CD127 and PD1-L
      and similar proportions expressed CD25, CTLA4, Fas-L and GITR-L. CMV-CD4+CD27
      CD28- TR expanded in response to IL-2, but not to CMV antigenic restimulation.
      The anti-proliferative effect of CMV-CD4+CD27-CD28- TR significantly decreased
      after granzyme B or TGFbeta inhibition. The CMV-CD4+CD27-CD28- TR of HIV-infected
      and uninfected donors had similar phenotypes and anti-proliferative potency, but
      HIV-infected individuals had higher proportions of CMV-CD4+CD27-CD28- TR. The CMV
      CD4+CD27-CD28- TR may contribute to the downregulation of CMV-specific and
      nonspecific immune responses of CMV-infected individuals.

PMID- 20034647
TI  - Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2)
      vaccine in mice and ferrets.
AB  - We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann
      Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the
      event of an H2 influenza pandemic. The AA ca virus was restricted in replication
      in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine
      elicited a >4-fold rise in hemagglutination-inhibition (HAI) titer and resulted
      in complete inhibition of viral replication following lethal homologous wild-type
      virus challenge. In ferrets, a single dose of the vaccine elicited a >4-fold rise
      in HAI titer and conferred complete protection against homologous wild-type virus
      challenge in the upper respiratory tract. In both mice and ferrets, the AA ca
      virus provided significant protection from challenge with heterologous H2 virus
      challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and
      efficacious against homologous and heterologous challenge in mice and ferrets,
      supporting the evaluation of this vaccine in clinical trials.

PMID- 20034648
TI  - Temporal analysis of HIV envelope sequence evolution and antibody escape in a
      subtype A-infected individual with a broad neutralizing antibody response.
AB  - The origin of broadly neutralizing HIV-specific antibodies and their relation to
      HIV evolution are not well defined. Here we examined virus evolution and
      neutralizing antibody escape in a subtype A infected individual with a broad,
      cross subtype, antibody response. The majority of envelope variants isolated over
      the first approximately 5 years after infection were poorly neutralized by
      contemporaneous plasma that neutralized variants from earlier in infection,
      consistent with a dynamic process of escape. The majority of variants could be
      neutralized by later plasma, suggesting these evolving variants may have
      contributed to the elicitation of new antibody responses. However, some variants
      from later in infection were recognized by plasma from earlier in infection,
      including one notably neutralization-sensitive variant that was sensitive due to
      a proline at position 199 in V2. These studies suggest a complex pattern of virus
      evolution in this individual with a broad NAb response, including persistence of
      neutralization-sensitive viruses.

PMID- 20034649
TI  - A jumbo phage infecting the phytopathogen Ralstonia solanacearum defines a new
      lineage of the Myoviridae family.
AB  - phiRSL1 is a jumbo myovirus stably and lytically infecting the phytopathogenic
      bacterium Ralstonia solanacearum. In this study, we investigate the infection
      cycle of varphiRSL1 and provide a genomic, proteomic and transcriptomic view of
      this phage. Its 231-kbp genome sequence showed many genes lacking detectable
      homologs in the current databases and was vastly different from previously
      studied phage genomes. In addition to these orphan proteins, varphiRSL1 was found
      to encode several enzymes that are unique among known viruses. These include
      enzymes for the salvage pathway of NAD(+) and for the biosynthetic pathways of
      lipid, carbohydrate and homospermidine. A chitinase-like protein was found to be
      a potential lysis enzyme. Our proteomics analysis suggests that varphiRSL1
      virions contain at least 25 distinct proteins. We identified six of them
      including a tail sheath protein and a topoisomerase IB by N-terminal sequencing.
      Based on a DNA microarray analysis, we identified two transcription patterns.

PMID- 20034650
TI  - Identification of a Hyphantria cunea nucleopolyhedrovirus (NPV) gene that is
      involved in global protein synthesis shutdown and restricted Bombyx mori NPV
      multiplication in a B. mori cell line.
AB  - We previously demonstrated that Bombyx mori nucleopolyhedrovirus (BmNPV)
      multiplication is restricted in permissive BmN-4 cells upon coinfection with
      Hyphantria cunea NPV (HycuNPV). Here, we show that HycuNPV-encoded hycu-ep32 gene
      is responsible for the restricted BmNPV multiplication in HycuNPV-coinfected BmN
      4 cells. The only homologue for hycu-ep32 is in Orgyia pseudotsugata NPV. hycu
      ep32 could encode a polypeptide of 312 amino acids, and it contains no
      characteristic domains or motifs to suggest its possible functions. hycu-ep32 is
      an early gene, and Hycu-EP32 expression reaches a maximum by 6 h postinfection.
      hycu-ep32-defective HycuNPV, vHycuDeltaep32, was generated, indicating that hycu
      ep32 is nonessential in permissive SpIm cells. In BmN-4 cells, HycuNPV infection
      resulted in a severe global protein synthesis shutdown, while vHycuDeltaep32 did
      not cause any specific protein synthesis shutdown. These results indicate that
      the restriction of BmNPV multiplication by HycuNPV is caused by a global protein
      synthesis shutdown induced by hycu-ep32 upon coinfection with HycuNPV.

PMID- 20034651
TI  - Human hepatoma cells transmit surface bound HIV-1 to CD4+ T cells through an ICAM
      1/LFA-1-dependent mechanism.
AB  - BACKGROUND: During the viremic phase of human immunodeficiency virus type-1 (HIV
      1) infection, hepatocytes are likely to be constantly exposed to circulating
      virions. Knowing that a contact between hepatocytes and CD4+ T lymphocytes is
      favoured by the local slow blood flow present within the liver, we hypothesize
      that hepatic cells can act as a viral reservoir and thus contribute to HIV-1
      propagation. RESULTS: We report that human hepatoma cells bind and internalize
      HIV-1 particles. Infection of CD4+ T cells was found to be much more efficient
      following a contact with virus-loaded hepatocytes than with cell-free virus.
      Additional studies suggest that infection of CD4+ T cells in trans with
      hepatocytes carrying virus is primarily due to surface bound HIV-1 particles and
      relies on LFA-1/ICAM-1 interactions. CONCLUSION: This work represents the first
      demonstration by which circulating CD4+ T cells can be potentially infected with
      HIV-1 through a contact with hepatocytes in the liver.

PMID- 20034652
TI  - Mitigation of methane emissions from constructed farm wetlands.
AB  - Constructed wetlands are increasingly used for water pollution treatment but may
      also be sources of the greenhouse gas CH(4). The effect of addition of two
      potential inhibitors of methanogenesis - iron ochre and gypsum - on net CH(4)
      emissions was investigated in a constructed wetland treating farm runoff in
      Scotland, UK. CH(4) fluxes from three 15-m(2) wetland plots were measured between
      January and July 2008 in large static chambers incorporating a tunable diode
      laser, with application of 5tonha(-1) ochre and gypsum in May. CH(4) fluxes were
      also measured from control and ochre- and gypsum-treated wetland sediment cores
      incubated at constant and varying temperature in the laboratory. Ochre addition
      suppressed CH(4) emissions by 64+/-13% in the field plot and >90% in laboratory
      incubations compared to controls. Gypsum application of 5tonha(-1) in the field
      and laboratory experiments had no effect on CH(4) emissions, but application of
      10tonha(-1) to a sediment core reduced CH(4) emissions by 28%. Suppression of
      CH(4) emissions by ochre application to sediment cores also increased with
      temperature; the reduction relative to the control increased from 50% at 17.5
      degrees C to >90% at 27.5 degrees C. No significant changes in N removal or pH
      and potentially-toxic metal content of sediments as the result of inhibitor
      application were detected in the wetland during the study.

PMID- 20034653
TI  - (40)Ar/(39)Ar dating, paleomagnetism, and tephrochemistry of Pliocene strata of
      the hominid-bearing Woranso-Mille area, west-central Afar Rift, Ethiopia.
AB  - (40)Ar/(39)Ar dating of tuffs and mafic lavas, tephra geochemistry, and
      paleomagnetic reversal stratigraphy have been used to establish the
      chronostratigraphy of the Pliocene hominid-bearing fossiliferous succession at
      Woranso-Mille, a paleontological study area in the western part of the central
      Afar region of Ethiopia. The succession in the northwestern part of the study
      area ranges in (40)Ar/(39)Ar age from 3.82-3.570 Ma, encompassed by paleomagnetic
      subchron C2Ar (4.187-3.596 Ma). One of the major tuff units, locally named the
      Kilaytoli tuff, is correlative on the basis of age and geochemistry to the
      Lokochot Tuff of the Turkana Basin. A hominid partial skeleton (KSD-VP-1) was
      found in strata whose precise stratigraphic position and age is still under
      investigation, but is believed to correspond to the later part of this interval.
      Woranso-Mille fills a significant gap in the fossil record of northeastern Africa
      at the time of the lower to middle Pliocene transition, when many extant species
      lineages of African fauna were established.

PMID- 20034654
TI  - Ozone precursors for the Sao Paulo Metropolitan Area.
AB  - Ozone represents the main atmospheric pollutant in the Sao Paulo Metropolitan
      Area (SPMA). In this region, its concentration exceeds the national air quality
      standards for several days out of the year. Ozone is a secondary pollutant and is
      a product of VOCs, NO(x), and sunlight. Thus, it is very difficult to elaborate
      efficient strategies for its reduction. Computational simulations may provide an
      interesting alternative to evaluate the many factors that affect ozone formation.
      In this study, the trajectory model OZIPR was used together with the SAPRC
      chemical mechanism to determine the incremental reactivity scale for VOCs in the
      SPMA. VOC input data were obtained from two campaigns that were performed in the
      studied area in 2006. Values for CO, NO(x), and meteorological parameters were
      obtained by automatic monitors. Five base-cases were created to verify the
      variation in maximum ozone concentration and thus determine the ozone formation
      potential of each VOC. NO(x) and VOC emissions were independently and
      simultaneously reduced by 5, 10, 20, and 30% to verify variations in ozone
      formation. With the simulator output data, ozone isopleths charts were generated
      for the city of Sao Paulo. Analysis of the obtained results shows that the most
      frequent compounds found among the ten main ozone precursors in Sao Paulo, using
      the reactivity scales created from the five base-cases, were: formaldehyde,
      acetaldehyde, propene, isoprene, cis-2-butene, and trans-2-butene, with
      formaldehyde being always the main ozone precursor compound. The simulations also
      show that an efficient strategy to decrease ozone concentrations in the SPMA
      would be to reduce total VOC emissions. The same strategy is not possible for
      NO(x), as the reduction of these pollutants would increase ozone concentrations.

PMID- 20034655
TI  - Association of serum TRAIL level with coronary artery disease.
AB  - Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member
      of the TNF ligand family, and is able to induce apoptosis in tumor cells.
      Emerging experimental findings suggest the involvement of TRAIL in vascular
      biology and atherosclerosis. However, little is known concerning the role of
      TRAIL in atherosclerosis in humans. We therefore examined whether serum TRAIL
      levels are associated with coronary artery disease (CAD). Serum TRAIL levels were
      measured by ELISA in 285 patients who underwent coronary angiography. Serum TRAIL
      level was significantly lower in patients with CAD (659.2+/-176.6 pg/ml) than in
      those without CAD (732.3+/-187.9 pg/ml, p=0.0016). Next, the number of diseased
      vessels was used to represent the severity of CAD. Serum TRAIL levels were
      inversely associated with the severity of CAD (p for trend=0.0005). In
      particular, TRAIL levels in patients with severe 3-vessel disease were
      significantly lower than those in subjects without CAD (602.9+/-150.0, 732.3+/
      187.9 pg/ml, respectively; p<0.05). Multivariable logistic regression analysis
      revealed that serum TRAIL levels were significantly associated with the presence
      of CAD (odds ratio, 0.68; 95% confidence interval 0.51-0.90; p=0.006). Serum
      TRAIL levels were inversely associated with the advanced CAD, suggesting that
      TRAIL may be useful as a biomarker of CAD severity.

PMID- 20034656
TI  - Decreased annexin A5 mRNA placental expression in pregnancies complicated by
      fetal growth restriction.
AB  - BACKGROUND: The placental anticoagulant protein Annexin A5 (ANXA5) is highly
      expressed on the apical surfaces of syncytiotrophoblasts and plays an important
      role in maintaining blood fluidity in the placental circulation. We investigated
      the mRNA and protein expression of ANXA5 in placentas from pregnancies
      complicated by fetal growth restriction (FGR) compared with uncomplicated
      pregnancies. MATERIALS AND METHODS: Placental tissue was collected from 18
      pregnancies complicated by FGR and 16 pregnancies with a normal outcome. ANXA5
      mRNA expression was quantified by Real-Time PCR (RT-PCR), and protein
      concentrations were measured by an enzyme-linked immunosorbent assay (ELISA).
      RESULTS: A decreased ANXA5 mRNA expression was observed in placenta samples from
      FGR-affected pregnancies compared to those from uncomplicated pregnancies.
      However, similar ANXA5 protein levels were measured in both specimen groups. No
      correlation was observed between ANXA5 mRNA and protein levels. CONCLUSIONS:
      Transcriptional ANXA5 down-regulation was demonstrated in FGR-affected
      pregnancies, although protein levels were similar in FGR-related placentas and
      controls. We can speculate that either recruitment of the protein from the
      bloodstream or increased apoptosis or post-transcriptional modifications occur,
      which affect ANXA5 protein levels in FGR-related placentas. Further studies are
      required to reveal the role of ANXA5 in FGR pathology.

PMID- 20034657
TI  - Robotic-assisted laparoscopic reconstruction of the upper urinary tract: tips and
      tricks.
AB  - OBJECTIVES: To examine whether simple tips and tricks provided in this manuscript
      and video make robotic reconstruction of the urinary tract possible from the
      renal calyx to the bladder. The da Vinci Surgical System (Intuitive Surgical,
      Inc., Sunnyvale, CA) has been widely accepted by urologists for complex
      reconstructive maneuvers such as radical prostatectomy and pyeloplasty. METHODS:
      The manuscript and accompanying video outline tips and tricks for patient
      selection, patient evaluation, port placement, dissection techniques, robotic
      docking, ureteral repair, and stent management for complex urinary tract
      reconstruction of the upper urinary tract from the level of the renal calyx to
      the bladder. RESULTS: Modifications such as port placement, robotic docking
      techniques, and ureter reconstruction have simplified the technique of complex
      robotic-assisted laparoscopic reconstruction of the urinary tract. CONCLUSIONS:
      Numerous scenarios can be encountered during robotic-assisted laparoscopic repair
      of the upper urinary tract. Simple tips and tricks provided in this manuscript
      and video make robotic reconstruction of the urinary tract possible from the
      renal calyx to the bladder.

PMID- 20034658
TI  - Lynch syndrome among gynecologic oncology patients meeting Bethesda guidelines
      for screening.
AB  - OBJECTIVE: Lynch syndrome (LS) is characterized by a high lifetime incidence of
      colorectal cancer and gynecologic malignancies such as endometrial and ovarian
      cancer. Identification of LS families is important as it allows for heightened
      cancer screening which decreases colorectal cancer mortality. The original 1996
      Bethesda guidelines included two gynecologic populations that should be further
      evaluated for LS: those with endometrial cancer before the age of 45 years and
      those with two LS-related cancers (i.e. synchronous endometrial and ovarian
      cancer). Our study aims to estimate the prevalence of LS in these two
      populations. METHODS: We utilized a diagnostic algorithm that included
      immunohistochemistry for mismatch repair protein expression followed by selective
      evaluation for microsatellite instability and MLH1 gene promoter methylation.
      RESULTS: Among 72 eligible patients, 9 (12%) had molecular findings consistent
      with LS: 6/50 (12%) in the early-onset endometrial cancer group and 3/22 (14%) in
      the synchronous primary cancer group. In an additional 3 cases, MLH1 silencing
      was due to promoter methylation: 1/50 (2%) in the early-onset endometrial cancer
      group and 2/22 (9%) in the synchronous primary cancer group. Of the 9 women with
      molecular criteria suggesting LS, only three had pedigrees meeting the Amsterdam
      criteria. CONCLUSIONS: A diagnostic algorithm can identify patients with LS and
      those who warrant further genetic testing. Our findings reinforce the
      recommendation that women diagnosed with endometrial cancer before the age of 45
      years and women with synchronous endometrial and ovarian cancer be screened for
      LS, irrespective of family history.

PMID- 20034659
TI  - Ovarian antral follicular dynamics in sheep revisited: comparison among estrous
      cycles with three or four follicular waves.
AB  - In this study, the characteristics of ovarian follicular waves and patterns of
      serum concentrations of follicle-stimulating hormone (FSH), estradiol, and
      progesterone were compared between cycles with three (n=9) or four (n=10)
      follicular waves in Western White Face (WWF) ewes (Ovis aries). Transrectal
      ultrasonography and blood sampling were performed daily during one cycle. Estrous
      cycles were 17.11+/-0.3 and 17.20+/-0.2 d long in cycles with three and four
      waves, respectively (P>0.05). The first interwave interval and the interval from
      the emergence of the final wave to the day of ovulation were longer in cycles
      with three waves compared with those in cycles with four waves (P<0.05). The
      growth phase (5.1+/-0.5 vs. 3.1+/-0.4 d) and life span (5.67+/-0.3 vs. 4.3+/-0.3
      d) of the largest follicle growing in the last or ovulatory wave was longer in
      cycles with three waves compared with that in cycles with four waves (P<0.05).
      The maximum diameter of the largest follicle was greater in the first wave and
      the ovulatory wave compared with that in other waves of the cycle (P<0.05). The
      regression phase of the largest follicle growing in the first wave was longer in
      cycles with three waves compared with that in cycles with four waves (4.44+/-0.4
      vs. 3.4+/-0.4 d; P<0.05). The length of the life span, regression phase, and,
      although not significant in every case, FSH peak concentration and amplitude
      decreased across the cycle (P<0.05). We concluded that estrous cycles with three
      or four follicular waves were confined within the same length of cycle in WWF
      ewes. In this study, there were no apparent endocrine or follicular
      characteristics that could explain the regulation of the different number of
      follicular waves (three vs. four) during cycles of similar length.

PMID- 20034660
TI  - Effects of flaxseed dietary supplementation on sperm quality and on lipid
      composition of sperm subfractions and prostatic granules in rabbit.
AB  - Lipids are the main structural/functional components of the sperm, and their
      composition may undergo a series of modifications in relation to either
      physiologic events (capacitation and acrosome reaction) and/or diet. The goals of
      the current study were (1) to investigate whether a flaxseed (FS) dietary
      supplementation could affect the lipid and fatty acid profile of sperm
      subfractions and of prostatic granules (PGs) and (2) to evaluate the effects of
      dietary FS on rabbit buck semen quality. Accordingly, 20 adult New Zealand White
      rabbits were fed ad libitum a control diet (CO) or a diet supplemented with 5%
      extruded FS. Integration of diet with FS, as a consequence of the linolenic acid
      (C18:3n-3; LNA; 56%), increased the dietary n-3/n-6 ratio and resulted in a
      substantial rearrangement of sperm fatty acid composition at the subcellular
      level, mainly of polyunsaturated fatty acid (PUFA)n-3 (8.3% vs. 14.3%, P<0.05).
      The lipid and fatty acid profiles of sperm tail membrane were the most affected,
      undergoing the following significant changes: (1) a reduction by half of linoleic
      acid (C18:2n-6; LA) and docosapentaenoic acid (22:5n-6; DPA), and a reduction of
      cholesterol (-70%); (2) a concomitant increase of LNA (+65%), docosahexaenoic
      acid (22:6n-3; DHA; +83%), and of oleic acid (C18:1n-9, +61%). As a consequence,
      the sperm of FS-fed rabbits had a twice higher n-3/n-6 ratio and
      phospholipid/cholesterol ratio compared with the control sperm. These changes
      might have been on the basis of the higher responsiveness to hypo-osmotic
      solution and, hence, the higher sperm track speed observed for the FS group.
      Also, the membrane integrity and viability of the LNA-enriched sperm were both
      improved. On the other hand, the presence of lignans in FS might have accounted
      for the reduction of sperm cholesterol in the semen of FS-treated rabbits. The
      responsiveness of sperm to acrosome reaction was not affected by the dietary
      treatment probably due to supranutritional level of vitamin E and to the higher
      number of PGs, which are known to play a key role in sperm capacitation. In
      conclusion, our data showed for the first time that the integration of FS into
      the rabbit diet may improve sperm quality by modifying the sperm lipid
      composition and that the sperm subfractions and the PGs respond differently to
      the FS-induced lipid manipulation.

PMID- 20034661
TI  - Loss of word-meaning with spared object semantics in a case of mixed primary
      progressive aphasia.
AB  - This article provides a detailed assessment of patient HT with a history of
      progressive language deterioration of approximately 6years presenting now as a
      fluent jargon aphasic with severe impairment of both speech production and
      comprehension. Neuropsychological testing of non-verbal cognitive functions
      showed no impairment, leading to the assumption of primary progressive aphasia
      (PPA). Contrary to the clinical criteria of the known PPA-subtypes there was
      nearly parallel decline of word comprehension and motor speech. HT also showed a
      significant dissociation between verbal and non-verbal semantic abilities
      resulting in severely impaired word comprehension with object semantics
      relatively spared. MRI scanning revealed pronounced focal atrophy of the left
      anterior temporal lobe and the left perisylvian region with relatively spared
      right temporal involvement. The clinical diagnostic criteria for PPA-subtypes do
      not seem to apply to the language features shown by our patient. The similarities
      and distinctions to semantic dementia and progressive non-fluent aphasia (PNFA)
      as subtypes of PPA will be discussed. The distinction between PNFA and SD may
      represent an oversimplification of the clinical presentations of PPA. It is also
      suggested that a mixed version of primary progressive aphasia should be taken
      into consideration as accepted clinical subtype.

PMID- 20034662
TI  - Multifunctional core-shell polymeric nanoparticles for transdermal DNA delivery
      and epidermal Langerhans cells tracking.
AB  - Skin is a highly immune-reactive tissue containing abundant antigen-presenting
      cells such as Langerhans cells (LCs), and thus is a favorable site for DNA
      immunization. This study developed a multifunctional core-shell nanoparticle
      system, which can be delivered transdermally into the epidermis via a gene gun,
      for use as a DNA carrier. The developed nanoparticles comprised a hydrophobic
      PLGA core and a positively-charged glycol chitosan (GC) shell. The core of the
      nanoparticles was used to load fluorescent quantum dots (QDs) for ultrasensitive
      detection of Langerhans cell migration following transdermal delivery, while a
      reporter gene was electrostatically adsorbed onto the GC shell layer of the
      nanoparticles. Results of fluorescence spectrophotometry, transmission electron
      microscopy, energy dispersive X-ray analysis, and X-ray diffraction measurement
      confirmed that the prepared nanoparticles had a core-shell structure with QDs in
      their core area. The surface charge of nanoparticles depended strongly on pH
      environment, enabling the intracellular release of the loaded DNA via a pH
      mediated mechanism. Using a mouse model, this study demonstrated that bombardment
      of nanoparticles transfected DNA directly into LCs present in the epidermis; the
      transfected LCs then migrated and expressed the encoded gene products in the skin
      draining lymph nodes. These observation results suggest that the developed
      nanoparticle system is suitable for monitoring and fine-tuning important
      functional aspects of the immune system, in conjunction with the loaded
      fluorescence, and thus has potential for use in immunotherapy and vaccine
      development.

PMID- 20034663
TI  - Integration of statistical modeling and high-content microscopy to systematically
      investigate cell-substrate interactions.
AB  - Cell-substrate interactions are multifaceted, involving the integration of
      various physical and biochemical signals. The interactions among these
      microenvironmental factors cannot be facilely elucidated and quantified by
      conventional experimentation, and necessitate multifactorial strategies. Here we
      describe an approach that integrates statistical design and analysis of
      experiments with automated microscopy to systematically investigate the
      combinatorial effects of substrate-derived stimuli (substrate stiffness and
      matrix protein concentration) on mesenchymal stem cell (MSC) spreading,
      proliferation and osteogenic differentiation. C3H10T1/2 cells were grown on type
      I collagen- or fibronectin-coated polyacrylamide hydrogels with tunable
      mechanical properties. Experimental conditions, which were defined according to
      central composite design, consisted of specific permutations of substrate
      stiffness (3-144 kPa) and adhesion protein concentration (7-520 microg/mL).
      Spreading area, BrdU incorporation and Runx2 nuclear translocation were
      quantified using high-content microscopy and modeled as mathematical functions of
      substrate stiffness and protein concentration. The resulting response surfaces
      revealed distinct patterns of protein-specific, substrate stiffness-dependent
      modulation of MSC proliferation and differentiation, demonstrating the advantage
      of statistical modeling in the detection and description of higher-order cellular
      responses. In a broader context, this approach can be adapted to study other
      types of cell-material interactions and can facilitate the efficient screening
      and optimization of substrate properties for applications involving cell-material
      interfaces.

PMID- 20034664
TI  - A nanostructured carbon-reinforced polyisobutylene-based thermoplastic elastomer.
AB  - This paper presents the synthesis and characterization of a polyisobutylene (PIB)
      based nanostructured carbon-reinforced thermoplastic elastomer. This
      thermoplastic elastomer is based on a self-assembling block copolymer having a
      branched PIB core carrying -OH functional groups at each branch point, flanked by
      blocks of poly(isobutylene-co-para-methylstyrene). The block copolymer has
      thermolabile physical crosslinks and can be processed as a plastic, yet retains
      its rubbery properties at room temperature. The carbon-reinforced thermoplastic
      elastomer had more than twice the tensile strength of the neat polymer, exceeding
      the strength of medical grade silicone rubber, while remaining significantly
      softer. The carbon-reinforced thermoplastic elastomer displayed a high T(g) of
      126 degrees C, rendering the material steam-sterilizable. The carbon also acted
      as a free radical trap, increasing the onset temperature of thermal decomposition
      in the neat polymer from 256.6 degrees C to 327.7 degrees C. The carbon
      reinforced thermoplastic elastomer had the lowest water contact angle at 82
      degrees and surface nano-topography. After 180 days of implantation into rabbit
      soft tissues, the carbon-reinforced thermoplastic elastomer had the thinnest
      tissue capsule around the microdumbbell specimens, with no eosinophiles present.
      The material also showed excellent integration into bones.

PMID- 20034665
TI  - In vitro generation of mechanically functional cartilage grafts based on adult
      human stem cells and 3D-woven poly(epsilon-caprolactone) scaffolds.
AB  - Three-dimensionally woven poly(epsilon-caprolactone) (PCL) scaffolds were
      combined with adult human mesenchymal stem cells (hMSC) to engineer mechanically
      functional cartilage constructs in vitro. The specific objectives were to: (i)
      produce PCL scaffolds with cartilage-like mechanical properties, (ii) demonstrate
      that hMSCs formed cartilage after 21 days of culture on PCL scaffolds, and (iii)
      study effects of scaffold structure (loosely vs. tightly woven), culture vessel
      (static dish vs. oscillating bioreactor), and medium composition (chondrogenic
      additives with or without serum). Aggregate moduli of 21-day constructs
      approached normal articular cartilage for tightly woven PCL cultured in
      bioreactors, were lower for tightly woven PCL cultured statically, and lowest for
      loosely woven PCL cultured statically (p<0.05). Construct DNA, total collagen,
      and glycosaminoglycans (GAG) increased in a manner dependent on time, culture
      vessel, and medium composition. Chondrogenesis was verified histologically by
      rounded cells within a hyaline-like matrix that immunostained for collagen type
      II but not type I. Bioreactors yielded constructs with higher collagen content
      (p<0.05) and more homogenous matrix than static controls. Chondrogenic additives
      yielded constructs with higher GAG (p<0.05) and earlier expression of collagen II
      mRNA if serum was not present in medium. These results show feasibility of
      functional cartilage tissue engineering from hMSC and 3D-woven PCL scaffolds.

PMID- 20034666
TI  - Cationic fluorine-containing amphiphilic graft copolymers as DNA carriers.
AB  - A series of cationic fluorine-containing amphiphilic graft copolymers P(HFMA-St
      MOTAC)-g-PEG comprising poly(hexafluorobutyl methacrylate) (PHFMA) poly(methacryl
      oxyethyl trimethylammonium chloride) (PMOTAC) polystyrene (PSt) backbones and
      poly(ethylene glycol) (PEG) side chains are synthesized as a type of non-viral
      gene vector. The copolymers self-assemble into spherical micelles in the aqueous
      media and turbidity and cytotoxicity measurements show that those micelles have
      excellent dispersive stability and low cytotoxicity. The interactions between the
      copolymers and calf-thymus DNA are studied by fluorescence spectroscopy and
      viscosity. The former discloses electrostatic interaction, hydrophobic
      interaction, and hydrogen bonding in the copolymer/DNA system, whereas the latter
      indicates that these graft copolymers can bind DNA via the electrostatic and
      classical intercalation modes. The DNA-binding capacity determined by the gel
      retardation assay and UV-visible spectrophotometry shows that the copolymers have
      good binding capacity to DNA and a high charge density or HFMA content in the
      copolymers bode well for DNA-binding. Transmission electron microscopy, photon
      correlation spectroscopy, and zeta potential data reveal that stable colloidal
      complexes (particles) can form easily between the copolymer micelles and DNA. Our
      results suggest that the copolymers are a promising non-viral vector in a gene
      delivery system.

PMID- 20034668
TI  - Combined analysis of minimal residual disease at two time points and its value
      for risk stratification in childhood B-lineage acute lymphoblastic leukemia.
AB  - The study was aimed to explore the value of minimal residual disease (MRD) for
      risk stratification in childhood precursor-B-acute lymphoblastic leukemia. MRD
      was monitored at two time points (TP1, after induction and TP2, before
      consolidation therapy) by quantitative detection of monoclonal immunoglobulin
      heavy chain gene rearrangements. This study stratified 105 patients into three
      MRD risk groups: standard-risk, MRD<10(-4) at both TP1 and TP2; high-risk,
      TP1>or=10(-2) or TP2>or=10(-3); and others were classified as intermediate-risk.
      We incorporated this MRD risk information to refine risk stratification among
      these patients and developed a new classification system that predicted the
      treatment outcomes more successfully than did the traditional risk classification
      criteria.

PMID- 20034669
TI  - Identification of in vitro upregulated genes in a modified live vaccine strain of
      Edwardsiella ictaluri compared to a virulent parent strain.
AB  - Using PCR-select subtractive cDNA hybridization technique, 41 in vitro expressed
      sequence tags (ESTs) were isolated from a modified live vaccine strain (AQUAVAC
      ESC, formerly RE-33) vs a virulent parent strain (EILO) of Edwardsiella ictaluri.
      Transcriptional levels of the 41 in vitro ESTs in the vaccine strain and the
      virulent strain were then evaluated by quantitative PCR (qPCR). The qPCR results
      revealed that 33 ESTs were consistently upregulated at least 3-fold in the
      modified live vaccine strain compared to the virulent parent strain. Of the 33
      upregulated ESTs, 11 were upregulated greater than 5-fold. The 41 ESTs were found
      to be homologues of genes involved in protective immunity (22%), adhesion (7%),
      cell growth and survival (20%), signaling (7%), metabolism (5%), and
      transcriptional regulation (5%). However, putative functions of 20% of the genes
      identified are currently unknown. Putative roles of some of the in vitro
      upregulated genes in protective immunity induced by the vaccine strain are
      discussed.

PMID- 20034670
TI  - Efficacy of an oral live vaccine for veterinary use against pseudotuberculosis.
AB  - Pseudotuberculosis, an infection caused by the ubiquitous enteropathogenic
      bacterium Yersinia pseudotuberculosis, is a recurrent veterinary problem in
      livestock and zoo animals. The only vaccine currently available in zoos is
      Pseudovac (a mixture of killed strains of various serotypes), but its efficacy is
      not well established. We show here that Pseudovac does not protect guinea pigs
      against a severe Y. pseudotuberculosis infection. We thus evaluated the
      possibility of using a live attenuated Y. pseudotuberculosis strain (IP32680) as
      an oral vaccine against animal pseudotuberculosis. We report that IP32680 is
      avirulent for guinea pigs and induces a strong IgG response against various
      serotypes of Y. pseudotuberculosis. One and two oral inoculations of IP32680
      provided 50% and 83% protection, respectively against a severe infection with a
      highly pathogenic strain. The avirulent Y. pseudotuberculosis IP32680 is
      therefore much more protective than Pseudovac and may represent a valuable oral
      vaccine against pseudotuberculosis in zoo animals.

PMID- 20034667
TI  - Abnormal calcium homeostasis in peripheral neuropathies.
AB  - Abnormal neuronal calcium (Ca2+) homeostasis has been implicated in numerous
      diseases of the nervous system. The pathogenesis of two increasingly common
      disorders of the peripheral nervous system, namely neuropathic pain and diabetic
      polyneuropathy, has been associated with aberrant Ca2+ channel expression and
      function. Here we review the current state of knowledge regarding the role of
      Ca2+ dyshomeostasis and associated mitochondrial dysfunction in painful and
      diabetic neuropathies. The central impact of both alterations of Ca2+ signalling
      at the plasma membrane and also intracellular Ca2+ handling on sensory neurone
      function is discussed and related to abnormal endoplasmic reticulum performance.
      We also present new data highlighting sub-optimal axonal Ca2+ signalling in
      diabetic neuropathy and discuss the putative role for this abnormality in the
      induction of axonal degeneration in peripheral neuropathies. The accumulating
      evidence implicating Ca2+ dysregulation in both painful and degenerative
      neuropathies, along with recent advances in understanding of regional variations
      in Ca2+ channel and pump structures, makes modulation of neuronal Ca2+ handling
      an increasingly viable approach for therapeutic interventions against the painful
      and degenerative aspects of many peripheral neuropathies.

PMID- 20034671
TI  - Effects of receiving additional off-site services on abstinence from illicit drug
      use among men on methadone: a longitudinal study.
AB  - Health and psychosocial service needs that may be co-morbid with opioid addiction
      may impede the success of drug treatment among patients attending methadone
      maintenance treatment programs (MMTPs). This longitudinal panel study
      investigates whether receipt of services from one or more helping professionals
      outside of the MMTP confers a benefit for drug treatment outcomes among a random
      sample of male MMTP patients (N=356). Each participant was interviewed 3 times,
      with 6 months between each interview. Since this observational study did not
      employ random assignment, propensity score matching was employed to strengthen
      causal validity of effect estimates. Results support hypotheses that receiving
      additional off-site services has significant beneficial effects in increasing the
      likelihood of abstaining from cocaine, heroin, and any illicit drug use over both
      the ensuing 6- and 12-month time periods. These findings indicate that receipt of
      additional medical and/or psychosocial services enhances the efficacy of
      methadone treatment in increasing abstinence from illicit drug use.

PMID- 20034672
TI  - Magic and artifice in the collection of Athanasius Kircher.
AB  - Situated at the center of intellectual life in baroque Rome, the museum
      administered by the Jesuit naturalist Athanasius Kircher (1602-1680)
      simultaneously instructed and bemused its audiences with an exuberant mix of
      exotic animals, classical art and technological marvels. Kircher's playful use of
      spectacle and his irrepressible fondness for "magic" were derided by
      contemporaries as frivolous wonder-mongering, but the lavish machines at the
      heart of his museum were more than mere showpieces. Instead, they presented
      audiences with a compelling vision of the natural world in which the hidden
      foundations of the universe could be captured and displayed by artifice.
      Kircher's collection was in itself a vast instrument of revelation, conceived on
      a grander scale than the telescope of Galileo but rooted all the same in
      contemporary scientific culture.

PMID- 20034673
TI  - Time spent with symptoms in a cohort of bipolar disorder outpatients in Spain: a
      prospective, 18-month follow-up study.
AB  - OBJECTIVE: Most research on the symptomatic burden in bipolar disorder has
      included patients enrolled exclusively from tertiary centers, and only a few
      studies have analyzed factors related to it. We investigated the proportion of
      time and the proportion of visits with symptoms in a cohort of bipolar
      outpatients followed-up for 18 months, as well as the associated variables.
      METHODS: 296 DSM-IV-TR bipolar outpatients were included in a naturalistic
      longitudinal follow-up study, with quarterly assessment. Euthymia was defined by
      a Hamilton Depression Rating Scale score <7 and Young Mania Rating Scale score
      <5. Depressive episode, by a HDRS score of >17, hypomanic episode by a YMRS score
      of 10-20, and manic episode by a YMRS score >20. Sub-syndromal symptoms required
      scores of 7-17 in HDRS and 5-10 in YMRS. Based on a detailed recall of affective
      symptoms in the time between interviews, time in episode was also determined.
      RESULTS: Patients were symptomatic for one third of the follow-up, and also one
      third of the visits. They spent three times more days depressed than manic or
      hypomanic. More prior affective episodes were related both to more time
      symptomatic and more visits with symptoms. LIMITATIONS: Some of the data were
      collected retrospectively. Treatment was naturalistic. CONCLUSIONS: In a bipolar
      outpatient cohort from Spain, time with symptoms was shorter than previously
      found in tertiary care settings. In accordance with other longitudinal studies,
      those patients spent much more time depressed than manic.

PMID- 20034674
TI  - Depression and platelet activation in outpatients with stable coronary heart
      disease: findings from the Heart and Soul Study.
AB  - Depression is associated with increased morbidity and mortality in patients with
      coronary heart disease (CHD). Increased platelet activation has been proposed as
      a potential mechanism by which depression may lead to adverse cardiovascular
      outcomes. In this cross-sectional study, we measured platelet activation in 104
      patients with stable CHD, including 58 with a current episode of major depression
      and 46 without past or current major depression. Participants were instructed not
      to take aspirin for 7 days prior to the study appointment. Platelet activation
      was measured by plasma concentrations of platelet factor 4 (PF4) and beta
      thromboglobulin (beta-TG), and by 24-h urinary concentrations of 11-dehydro
      thromboxane B(2) (TBXB2). We observed no differences in the mean levels of PF4, B
      TG or TBXB2 in patients with and without major depression. Results were unchanged
      after adjustment for age, smoking, use of aspirin, and use of any psychotropic
      medication. We found no evidence of an association between major depression and
      platelet activation as measured by plasma concentrations of PF4 and beta-TG, or
      urinary TBXB2 in 104 outpatients with stable CHD. These findings do not support a
      role for platelet activation in the association between depression and
      cardiovascular disease among patients with stable CHD.

PMID- 20034675
TI  - Maintenance electroconvulsive therapy: an alternative treatment for refractory
      schizophrenia and schizoaffective disorders.
AB  - This retrospective chart review of a clinical cohort of 19 refractory
      schizophrenic or schizoaffective patients treated with maintenance
      electroconvulsive therapy addresses the indications for this treatment, its
      efficacy, and its impact on daily functioning and hospitalizations. Maintenance
      electroconvulsive therapy combined with medication appears to be an efficient
      alternative to pharmacological treatment alone.

PMID- 20034676
TI  - Recollection deficiencies in patients with major depressive disorder.
AB  - Neuropsychological research suggests that recognition memory (RM) and recall
      memory are impaired in patients with a major depressive disorder or a dysphoric
      mood state. This study examines the proposal that abnormalities in recollection
      (a form of recall) result from a breakdown in frontal strategic memory processes
      involved in encoding and retrieval, and executive functions linked to reality
      monitoring, planning, problem-solving, reasoning and decision-making. We
      investigated two predictions arising from this theory. Firstly, patients
      diagnosed with a major depressive disorder (MDD) will display a dissociation
      between (deficient) recollection and (preserved) familiarity. Secondly, if
      recollection impairments are indicative of a breakdown in prefrontal strategic
      memory processes which are dependent, at least in part, on executive processes,
      then an explicit correlational approach predicts that recollection will be
      positively associated with the severity of executive dysfunction in MDD patients.
      The remember/know paradigm was used to investigate RM for words and neutral faces
      in 16 MDD patients and 16 healthy volunteers, matched for age, gender and
      estimates of premorbid IQ. Measures of executive function included working
      memory, reasoning and decision-making. Applying the Dual Process Signal Detection
      interpretation of the remember/know data, the MDD group displayed significant
      impairments in RM and recollection rates for both verbal and neutral facial
      memoranda. In contrast, familiarity-aware rates were preserved. There was no
      evidence of executive dysfunction in the patient group, and little evidence that
      recollection rates correlated with executive function. Furthermore, a single
      process signal detection approach suggested that the MDD patients displayed a
      reduction in sensitivity for RM and remember rates but not know responses. The
      criteria for detecting studied from unstudied items, and remembering from
      knowing, were the same in both patient and healthy control groups. Taken
      together, these findings are consistent with the view that MDD is marked by a
      decline in RM, which is underpinned by an impairment in recollection rather than
      familiarity processes. The extent to which the recollection deficiencies arise
      from disruption of strategic memory and executive processes requires further
      investigation.

PMID- 20034677
TI  - The effect of beta-glucans on porcine leukocytes.
AB  - beta-Glucans are conserved glucose polymers found in the cell walls of plants,
      fungi, yeasts and bacteria. They have the capacity to activate innate immunity,
      thereby enhancing defence barriers. Besides differences in type of linkage and
      branching, beta-glucans can vary in solubility, molecular mass, tertiary
      structure, polymer charge and solution conformation. All these characteristics
      may influence their immunomodulating effects. In this study, the effect of seven
      beta-glucans that differed in origin (fungi, yeast, seaweed, bacteria or algae)
      and structure (linear or branched; soluble, gel or particulate) were tested on
      peripheral blood mononuclear cells (PBMC) and neutrophils of the pig. We looked
      at lymphocyte proliferation, reactive oxygen species (ROS), production by
      neutrophils and monocytes and cytokine production. The soluble beta-glucans
      Laminarin and Sleroglucan did not activate ROS-production of monocytes and
      neutrophils while the particulate beta-glucans (beta-glucan from algae (Euglena
      gracilis)) and glucan preparations from baker's yeast (Macrogard, Saccharomyces
      cerevisiae and Zymosan) had a stimulating effect. The highest stimulation of
      lymphocyte proliferation occurred by Curdlan (bacteria), Zymosan and the beta
      glucan of E. gracilis, especially at high concentrations (200 microg/ml and 800
      microg/ml). TNF-alpha was particularly stimulated by Macrogard and S. cerevisiae,
      while all beta-glucans (except Laminarin) induced IL-1beta. Furthermore, it was
      interesting that all beta-glucans and in particular Curdlan, gave rise to IL-10
      secretion, whereas any beta-glucan induced the release of IL-8, IL-4, IL-12, IL-6
      or IFN-gamma.

PMID- 20034678
TI  - Expression of Toll-like receptor 2 in duodenal biopsies from dogs with
      inflammatory bowel disease is associated with severity of disease.
AB  - There is growing evidence that aberrant innate immune responses towards the
      bacterial flora of the gut play a role in the pathogenesis of canine inflammatory
      bowel disease (IBD). Toll-like receptors (TLR) play an important role as primary
      sensors of invading pathogens and have gained significant attention in human IBD
      as differential expression and polymorphisms of certain TLR have been shown to
      occur in ulcerative colitis (UC) and Crohn's disease (CD). The aim of the current
      study was to evaluate the expression of two TLR important for recognition of
      commensals in the gut. TLR2 and TLR4 mRNA expression in duodenal biopsies from
      dogs with IBD was measured and correlated with clinical and histological disease
      severity. Endoscopic duodenal biopsies from 20 clinical cases and 7 healthy
      control dogs were used to extract mRNA. TLR2 and TLR4 mRNA expression was
      assessed using quantitative real-time PCR. TLR2 mRNA expression was significantly
      increased in the IBD dogs compared to controls, whereas TLR4 mRNA expression was
      similar in IBD and control cases. In addition, TLR2 mRNA expression was mildly
      correlated with clinical severity of disease, however, there was no correlation
      between TLR2 expression and histological severity of disease.

PMID- 20034679
TI  - Clinical, electrophysiological and pathologic correlations in a severe murine
      experimental autoimmune neuritis model of Guillain-Barre syndrome.
AB  - Severe murine experimental autoimmune neuritis (sm-EAN) in SJL/J mice is a
      recently described, but incompletely characterized mouse model of Guillain-Barre
      syndrome (GBS). Electrophysiological and pathologic characterization during the
      disease course is a necessary prerequisite to designing mechanistic studies that
      may be relevant to GBS pathogenesis. Sm-EAN is a monophasic disorder with
      electrophysiological evidence for a diffuse demyelinating polyneuropathy with
      axonal loss at peak severity. Regression analyses demonstrated strong
      correlations between neuromuscular severity scores and electrophysiological
      parameters during the disease course. Progressive multi-focal or diffuse
      demyelination with axonal loss was observed pathologically in sciatic nerves in
      association with mononuclear cell infiltrates (F4/80+ macrophages>CD3+ T
      lymphocytes>CD19+ B-lymphocytes), peaking at maximal severity. Regression
      analyses demonstrated strong correlations between severity scores and
      inflammatory cell counts. The correlative data imply that mononuclear
      infiltration, as well as demyelination and axonal loss are directly related to
      the observed neuromuscular weakness in sm-EAN. The high induction rates, as well
      as pathologic similarities with AIDP make sm-EAN a robust model to study the
      pathogenesis of human peripheral nerve inflammation using objective outcome
      measures.

PMID- 20034681
TI  - Effects of silver nanoparticles on the development and histopathology biomarkers
      of Japanese medaka (Oryzias latipes) using the partial-life test.
AB  - Silver nanoparticles (AgNPs) have emerged as an important class of nanomaterials
      and are currently used in a wide range of industrial and commercial applications.
      This has caused increasing concern about their effects on the environment and to
      human health. Using Japanese medaka (Oryzias latipes) at early-life stages as
      experimental models, the developmental toxicity of silver nanoparticles was
      investigated following exposure to 100-1000 MUg/L homogeneously dispersed AgNPs
      for 70 days, and developmental endpoints were evaluated by microscopy during
      embryonic, larval and juvenile stages of development in medaka. Meanwhile,
      histopathological changes in the larval eye were evaluated. Retarded development
      and reduced pigmentation were observed in the treated embryos by AgNPs at high
      concentrations (>= 400 MUg/L). Maximum width of the optic tectum, as an indicator
      of midbrain development, decreased significantly in a dose-related manner.
      Furthermore, silver nanoparticles exposure at all concentrations induced a
      variety of morphological malformations such as edema, spinal abnormalities,
      finfold abnormalities, heart malformations and eye defects. Histopathological
      observations also confirmed the occurrence of abnormal eye development induced by
      AgNPs. The data showed non-linear or U-shaped dose-response patterns for growth
      retardation at 5 days of postfertilization, as well as the incidence of
      abnormalities. Preliminary results suggested that the developmental process of
      medaka may be affected by exposure to silver nanoparticles. Morphological
      abnormalities in early-life stages of medaka showed the potential developmental
      toxicities of silver nanoparticles. Further research should be focused on the
      mechanisms of developmental toxicity in fish exposed to silver nanoparticles.

PMID- 20034680
TI  - Increased expression of B cell-associated regulatory cytokines by glatiramer
      acetate in mice with experimental autoimmune encephalomyelitis.
AB  - B cells are of increasing importance as a target for multiple sclerosis
      treatment. Here we show that GA treatment of mice with experimental autoimmune
      encephalomyelitis (EAE) biases cytokine production by B cells towards cytokines
      associated with regulation in MS including interleukin (IL)-4, -10 and -13 and
      reduces pro-inflammatory IL-6, IL-12, and TNF alpha levels. GA also down
      regulates expression of B cell-activating factor (BAFF) of the TNF family and a
      proliferation-inducing ligand (APRIL), as well as the BAFF receptor in mice with
      EAE. Thus, GA impacts both B cell survival and B cell cytokine production during
      CNS inflammatory disease in an EAE model.

PMID- 20034682
TI  - Hard to heal pressure ulcers (stage III-IV): efficacy of injected activated
      macrophage suspension (AMS) as compared with standard of care (SOC) treatment
      controlled trial.
AB  - The objective of this study was to compare local injections of AMS with SOC
      treatments for stage III and IV pressure ulcers in elderly patients. It was
      designed as historically prospective 2-arms non-parallel open controlled trial,
      and conducted in a department of geriatric medicine and rehabilitation of a
      university affiliated tertiary hospital. We studied 100 consecutive elderly
      patients with a total of 216 stage III or IV pressure ulcers, 66 patients were
      assigned to the AMS group and had their wounds injected, while 38 patients were
      assigned to the SOC group. Primary outcome was rate of complete wound closure.
      Time to complete wound closure and 1-year mortality served as secondary outcomes.
      Statistical analyses were performed at both patient and wound levels. Percentage
      of completely closed wounds (wound level and patient level) were significantly
      better (p<0.001/p<0.001, respectively) in all patients in favor of AMS, as well
      as in the subset of diabetic patients (p<0.001/p<0.001). Similarly, AMS proved
      significantly better for the subset of those with leg ulcers and with baseline
      wounds <=15 cm(2), compared with SOC. There were no statistically significant
      differences with regard to time to complete closure or 1-year mortality rates in
      the two groups. It is concluded that there is a significant difference in favor
      of stage III and IV wound closure rates by AMS, as compared with SOC treatments.

PMID- 20034683
TI  - Upright versus supine position in examining a patient with hypertrophic
      cardiomyopathy.

PMID- 20034684
TI  - Genetic basis of sudden cardiac death due to emotional trauma in apparently
      healthy individuals.

PMID- 20034685
TI  - Combined effects of atorvastatin and metformin on glucose-induced variations of
      inflammatory process in patients with diabetes mellitus.
AB  - BACKGROUND: Statin treatment improves survival in patients with atherosclerosis,
      but their effect on the glucose-induced variations of inflammatory markers, is
      unknown. We examined the effect of combined therapy with atorvastatin and
      metformin on glucose-induced variations of inflammatory molecules in patients
      with newly diagnosed diabetes mellitus type 2 (DM). METHODS: Thirty five subjects
      with newly diagnosed DM were randomized to receive metformin 850 mg/d (M, n=17)
      or metformin 850 mg/d+atorvastatin 10mg (n=18). All subjects underwent glucose
      loading (75 g oral glucose) at baseline and after 12 weeks of treatment. Blood
      samples were obtained at baseline and 3h post-loading, while serum tumor necrosis
      factor alpha (TNF-alpha) levels were determined at baseline and at 3h. RESULTS:
      Serum TNF-alpha remained unchanged in metformin at baseline (1.36+/-0.18 to
      1.47+/-0.21 pg/ml p=NS) and after treatment (1.44+/-0.71 to 1.31+/-0.17 pg/ml,
      p=NS), while it was reduced in metformin+atorvastatin (2.3+/-0.3 to 2.0+/-0.4
      pg/ml, p=NS at baseline and 1.80+/-0.2 to 1.65+/-0.2 pg/ml, p=0.03 after
      treatment). CONCLUSIONS: Interestingly, the combination of metformin and
      atorvastatin partly prevents the glucose-loading induced elevation of glucose
      levels (at 1 h), suggesting a better response to glucose intake than monotherapy
      with metformin. In addition, combined treatment with atorvastatin and metformin
      reduces the post-glucose loading levels of TNF-alpha compared to metformin
      monotherapy.

PMID- 20034686
TI  - Left ventricular support device for cardiogenic shock during myocardial
      infarction due to stent thrombosis: a single centre experience.
AB  - BACKGROUND: Stent thrombosis (ST) is a new, rare, cause of STEMI. Few data are
      available about incidence and clinical impact of shock complicating acute
      myocardial infarction due to ST (st-STEMI). METHODS: From January 2004 to March
      2007, 92 st-STEMI patients were observed: 14 (15.2%) of them presented with
      cardiogenic shock and were evaluated in the present analysis. In particular,
      clinical and angiographic characteristics of survivors and non-survivors to PCI
      were compared. RESULTS: St-STEMI was related to left main or multivessels stent
      thrombosis in 35.7% of cases; whereas in 93% of cases st-STEMI occurred in a
      territory with previous myocardial infarction. All patients underwent IABP
      implantation immediately before coronary angiography, whereas Impella LP 2.5 pump
      was used in 21% of cases when persistent cardiac low-output signs were recorded.
      PCI was successful in 80% of cases. In-hospital survival was 28.6%. Death
      occurred within the first 48 h in the majority of patients. At six-months all
      patients survived to the acute phase were alive. Survivors had significantly
      lower thrombus grade after wire passage (p=0.03) and, albeit not significant,
      they showed a higher rate of very late ST, longer times from symptoms onset to
      revascularization, and higher TIMI flow grade either before and after PCI.
      CONCLUSION: The incidence of cardiogenic shock in st-STEMI is high, particulary
      it seems to be two times higher than the rate reported during myocardial
      infarction. One third of cases is related to left main or multiple vessels ST.
      Shock in st-STEMI represents a dramatic event with very low in-hospital and early
      survival.

PMID- 20034687
TI  - Prospective assessment of multiple cardiac papillary fibroelastomas: an
      echocardiographic and surgical study.
AB  - Multiple cardiac papillary fibroelastomas (PFEs) are thought to account for less
      than 10% of patients with PFE. We aimed at evaluating the frequency and location
      of multiple PFEs and the reliability of transthoracic (TTE) and transoesophageal
      (TEE) echocardiography in diagnosing multiple PFEs. Twenty-six consecutive
      patients (52+/-14 years, 65% males) with pathologically confirmed PFE had 21 PFEs
      diagnosed by TTE, 33 by TEE, and 62 at surgery. Eight patients (31%) had multiple
      PFEs found either by TEE or at surgery. Aortic valve was involved in 75% of
      patients with multiple PFEs and left ventricle in 38% of patients. The
      sensitivity of TTE in diagnosing any PFEs was 51.3% and 76.9% for TEE. Our study
      emphasizes the high frequency of multiple PFEs, the need of TEE for all presumed
      PFE and the need for careful assessment of left-sided endocardial surfaces,
      especially of the aortic valve, during PFE excision.

PMID- 20034688
TI  - Frequency of vacuolating cytotoxin A (VacA)-positive Helicobacter pylori
      seropositivity and TGF-beta1 decrease in atrial fibrillation.
AB  - The study was performed to determine whether there were any associations of VacA
      positive Helicobacter pylori and TGF-beta1 with atrial fibrillation (AF). The
      serum levels of antibodies to H. pylori and VacA, and cytokines were assessed
      using ELISA in 96 subjects. While elevated levels of TNF-alpha, IL-6 and CRP were
      associated with AF, TGF-beta(1) was significantly lowered in AF patients
      (p=0.021). In addition, AF was associated with elevated levels of antibodies to
      VacA (p=0.023), compared to the control group. Accordingly, the chronic infection
      of VacA(+)H. pylori may increase the risk for AF by inducing systemic
      inflammation mediated, partly by suppressed TGF-beta(1) and elevated
      proinflammatory cytokines.

PMID- 20034689
TI  - Midregional pro-A-type natriuretic peptide for the evaluation of exercise
      intolerance.
AB  - The aim of this study was to determine the accuracy of midregional pro-A-type
      natriuretic peptide (MR-proANP) for the identification of a cardiocirculatory
      exercise limitation (CL) as assessed by cardiopulmonary exercise testing (CPET)
      and to compare it to B-type natriuretic peptide (BNP). Among 94 patients with
      CPET data fulfilling criteria for appropriate effort and sufficient diagnostic
      certainty, 27 (29%) had CL. The areas under the receiver-operator-characteristic
      curve for MR-proANP and BNP to identify CL were 0.84 and 0.79 respectively
      (p=0.17). In conclusion, MR-proANP had a comparable accuracy to BNP for the
      identification of CL and might be a valuable assistance for the differentiation
      of exercise intolerance.

PMID- 20034690
TI  - Serological survey of bovine brucellosis in barka and arado breeds (Bos indicus)
      of western Tigray, Ethiopia.
AB  - A cross sectional study was conducted to determine the seroprevalence and
      associations with potential risk factors of brucellosis in indigenous cattle
      breeds of Western Tigray zone, North West Ethiopia. A total of 1968 cattle were
      examined between October 2007 and April 2008. Of these, 1120 cattle were from
      semi-intensive production system composed mainly of barka breed while 848 cattle
      were from extensive system with arado breed being predominant. Sera were screened
      using Rose Bengal Plate Test (RBPT) and positive samples were then confirmed by
      Complement Fixation Test (CFT). The overall individual animal-level prevalence
      was 4.9%. Brucellosis seroprevalence was higher in herds reared under semi
      intensive production systems. 7.7% and 63.6% prevalence were found at individual-
      and herd-level in the semi-intensive system, respectively. 1.2% and 3.3% were the
      figures for the extensive system. Both individual- and herd-level seroprevalence
      were higher in Mykadra and Bereket towns among all investigated towns. Though the
      odds ratio for Humera was more than two, seroprevalences across the three
      districts in the extensive production system were comparable. Herd size, age,
      sex, and husbandry practices were significantly associated with seropositivity
      and brucellosis increased the calving interval. Higher risk to infection was
      found in barka breed than arado in the semi-intensive production system but not
      in the extensive production system. Breed management systems, but not breed
      caused breed susceptibility variation. A high prevalence of brucellosis in barka
      breed in the study area indicates that it might serve as source of infection for
      others in the region. Hence, screening tests aiming at culling seropositive barka
      was recommended before distribution to other poverty-prone areas of the region.

PMID- 20034691
TI  - Mechanism of inactivation of murine norovirus-1 by high pressure processing.
AB  - Murine norovirus-1 (MNV) is currently the most suitable surrogate for human
      norovirus. The mechanism of MNV-1 inactivation by high pressure processing (HPP)
      was investigated. HPP-treated MNV could not bind to its target receptor and
      therefore could not initiate infection of mouse RAW cells. The integrity of the
      capsid was not affect by HPP. Partial motif changes of the viral capsid caused by
      HPP were accessed by induced sensitivity to proteinase K.

PMID- 20034692
TI  - Using anthropometric indices to predict cardio-metabolic risk factors in
      Australian indigenous populations.
AB  - AIMS: To compare the predictive power of anthropometric indices (BMI, waist
      circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR))
      for diabetes, hypertension and dyslipidemia in Australian Aboriginal and Torres
      Strait Islander (TSI) adults. METHODS: Cross-sectional study of 2862 Indigenous
      Australians aged over 15 living in rural communities in Far North Queensland
      during 1999-2001. The predictive values of anthropometric indices for cardio
      metabolic disorders were compared using receiver operating characteristic (ROC)
      analysis. RESULTS: BMI was the poorest predictor while WHpR was the best among
      the four measures. The optimal WHtR and WHpR cut-off points for the cardio
      metabolic risks in both women and men in the two Indigenous populations were 0.5
      0.6 and 0.9 respectively. Optimal BMI cut-offs for diabetes, hypertension, and
      dyslipidemia were much lower in Aborigines than the recommended WHO BMI cut-offs,
      while those in TSIs were around WHO BMI criteria. The optimal WC cut-points
      varied by gender and ethnicity. CONCLUSIONS: BMI was not a good discriminator of
      cardio-metabolic risk factors in Australian Indigenous populations compared with
      other anthropometric indices. WHpR is more closely associated with the risk of
      cardio-metabolic in these high-risk populations.

PMID- 20034693
TI  - Liver grafts from anti-hepatitis B core positive donors: a systematic review.
AB  - BACKGROUND & AIMS: Although hepatitis B virus (HBV) transmission after liver
      transplantation of grafts from HBsAg-negative, anti-HBc positive donors is well
      established, the growing organ shortage favours the use of such marginal grafts.
      We systematically evaluated the risk of HBV infection after liver transplantation
      with such grafts and the effect of anti-HBV prophylaxis. METHODS: We performed a
      literature review over the last 15 years identifying 39 studies including 903
      recipients of anti-HBc positive liver grafts. RESULTS: Recurrent HBV infection
      developed in 11% of HBsAg-positive liver transplant recipients of anti-HBc
      positive grafts, while survival was similar (67-100%) to HBsAg-positive
      recipients of anti-HBc negative grafts. De novo HBV infection developed in 19% of
      HBsAg-negative recipients being less frequent in anti-HBc/anti-HBs positive than
      HBV naive cases without prophylaxis (15% vs 48%, p<0.001). Anti-HBV prophylaxis
      reduced de novo infection rates in both anti-HBc/anti-HBs positive (3%) and HBV
      naive recipients (12%). De novo infection rates were 19%, 2.6% and 2.8% in HBsAg
      negative recipients under hepatitis B immunoglobulin, lamivudine and their
      combination, respectively. CONCLUSIONS: Liver grafts from anti-HBc positive
      donors can be safely used, preferentially in HBsAg-positive or anti-HBc/anti-HBs
      positive recipients. HBsAg-negative recipients should receive prophylaxis with
      lamivudine, while both anti-HBc and anti-HBs positive recipients may need no
      prophylaxis at all.

PMID- 20034694
TI  - Hepatitis C virus viremia and low platelet count: a study in a hepatitis B & C
      endemic area in Taiwan.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection has been shown to be
      associated with a low platelet count. This study aimed to elucidate the
      association between virologic status and platelet count in individuals with HCV
      infection. METHODS: A large-scale survey, enrolling 11,239 residents, was
      conducted in the Kaohsiung area of Taiwan. Serum HCV RNA and non-invasive markers
      of fibrosis (FibroTest) were tested for antibody to HCV (anti-HCV)-positive
      subjects. The platelet counts of age- and sex-matched, biopsy-proven, hospital
      based patients and community-based patients with minimal fibrosis were compared.
      RESULTS: Anti-HCV was positive in 703 (6.2%) subjects and was significantly
      associated with older age, female sex, abnormal alanine aminotransferase (ALT)
      value and low platelet count (<150,000/microl). The independent factors
      significantly associated with low platelet count were abnormal ALT value (odds
      ratio [OR]: 3.70, 95% confidence intervals [CI]: 2.18-6.28) and positive HCV RNA
      (OR: 2.00, 95% CI: 1.01-3.97). After adjustment for the fibrosis, HCV RNA
      remained significantly associated with platelet counts. CONCLUSIONS: Our results
      evaluating the association between platelet count and HCV viremia and taking the
      influences of fibrosis into consideration implicate that platelets may be
      affected directly by HCV.

PMID- 20034696
TI  - Changes in clinical practice and patient disposition following the introduction
      of point-of-care testing in a rural hospital.
AB  - OBJECTIVES: To determine whether the practical impact of point-of-care (POC)
      laboratory testing justifies its use in a remote rural hospital. METHODS: Test
      indication, pre-test differential diagnosis and planned patient disposition were
      recorded over 6 months before and after POC test use in Rawene hospital, in New
      Zealand's remote north. Doctors recorded impacts on patient treatments (no
      change, some change or a significant change). Comparisons were made using paired
      t-tests or chi(2) tests. An analysis of cost versus tangible benefits was also
      undertaken. RESULTS: 269 POC tests were undertaken for 177 patients. POC tests
      significantly increased diagnostic certainty (2.5 diagnoses pre-test versus 1.3
      diagnoses post-test (p<0.001)), and altered disposition for 43% of patients
      (p<0.001) by reducing transfers to base hospital by 62% (52 pre-test and 20 post
      test) and increasing discharges by 480% (7 pre-test and 34 post-test).
      Substantial treatment change was reported in 75% of cases, some change in 22%,
      and no change in 3%. Overall financial benefits amounted to $452,360 annually.
      CONCLUSIONS: POC testing helps address inequity in acute health care provision
      for a disadvantaged rural community by allowing rural clinicians access to
      necessary and critical investigations in a clinically relevant turn-around time.

PMID- 20034695
TI  - Liver disease associated with canalicular transport defects: current and future
      therapies.
AB  - Bile formation at the canalicular membrane is a delicate process. This is
      illustrated by inherited liver diseases due to mutations in ATP8B1, ABCB11,
      ABCB4, ABCC2 and ABCG5/8, all encoding hepatocanalicular transporters. Effective
      treatment of these canalicular transport defects is a clinical and scientific
      challenge that is still ongoing. Current evidence indicates that ursodeoxycholic
      acid (UDCA) can be effective in selected patients with PFIC3 (ABCB4 deficiency),
      while rifampicin reduces pruritus in patients with PFIC1 (ATP8B1 deficiency) and
      PFIC2 (ABCB11 deficiency), and might abort cholestatic episodes in BRIC (mild
      ATP8B1 or ABCB11 deficiency). Cholestyramine is essential in the treatment of
      sitosterolemia (ABCG5/8 deficiency). Most patients with PFIC1 and PFIC2 will
      benefit from partial biliary drainage. Nevertheless liver transplantation is
      needed in a substantial proportion of these patients, as it is in PFIC3 patients.
      New developments in the treatment of canalicular transport defects by using
      nuclear receptors as a target, enhancing the expression of the mutated
      transporter protein by employing chaperones, or by mutation specific therapy show
      substantial promise. This review will focus on the therapy that is currently
      available as well as on those developments that are likely to influence clinical
      practice in the near future.

PMID- 20034697
TI  - B-LUT: Fast and low memory B-spline image interpolation.
AB  - We propose a fast alternative to B-splines in image processing based on an
      approximate calculation using precomputed B-spline weights. During B-spline
      indirect transformation, these weights are efficiently retrieved in a nearest
      neighbor fashion from a look-up table, greatly reducing overall computation time.
      Depending on the application, calculating a B-spline using a look-up table,
      called B-LUT, will result in an exact or approximate B-spline calculation. In
      case of the latter the obtained accuracy can be controlled by the user. The
      method is applicable to a wide range of B-spline applications and has very low
      memory requirements compared to other proposed accelerations. The performance of
      the proposed B-LUTs was compared to conventional B-splines as implemented in the
      popular ITK toolkit for the general case of image intensity interpolation.
      Experiments illustrated that highly accurate B-spline approximation can be
      obtained all while computation time is reduced with a factor of 5-6. The B-LUT
      source code, compatible with the ITK toolkit, has been made freely available to
      the community.

PMID- 20034698
TI  - DC-SIGN and SRCL bind glycans of carcinoembryonic antigen (CEA) and CEA-related
      cell adhesion molecule 1 (CEACAM1): recombinant human glycan-binding receptors as
      analytical tools.
AB  - Members of the family of carcinoembryonic antigen (CEA)-related cell adhesion
      molecules (CEACAMs) belonging to the immunoglobulin (Ig) superfamily are
      expressed in a variety of normal and malignant human tissues. As components of
      the cell membrane, these glycoproteins can make contact with adjacent cells.
      CEACAM1 and CEACAM5 (CEA) express Lewis(x) (Le(x)) structures. As shown by mass
      spectrometry in conjunction with enzymatic digestion, CEACAM1 contains at least
      seven Le(x) residues. Fucosyltransferase IX is the main fucosyltransferase
      responsible for attachment of terminal fucose, the key feature of the Le(x)
      structure, to CEA and CEACAM1. The Le(x) residues of both, CEACAM1 and CEA,
      interact with the human Le(x)-binding glycan receptors DC-SIGN and SRCL. Since
      subpopulations of human macrophages express DC-SIGN or SRCL, Le(x)-carrying
      CEACAMs may modulate the immune response in normal tissues such as the human
      placenta or in malignant tumours, for example in colorectal, pancreatic or lung
      carcinomas.

PMID- 20034699
TI  - Regulation of cell behaviour by plant receptor kinases: Pattern recognition
      receptors as prototypical models.
AB  - In this review we focus on pattern recognition receptors in plants that detect
      extracellular signals indicative for pathogen attack and injury. We start out
      with a discussion on FLS2, which binds and responds to bacterial flagellin, and
      then concentrate on ligand-receptor interactions as initial steps in the
      molecular receptor activation process. Comparison with other receptor kinases,
      whether involved in plant immunity or regulation of other cellular programs,
      might indicate common principles of receptor activation.

PMID- 20034700
TI  - Glycostructures in biological systems - synthesis and function.

PMID- 20034701
TI  - Regulation of the plant plasma membrane H+-ATPase by its C-terminal domain: what
      do we know for sure?
AB  - The plant plasma membrane H(+)-ATPase is kept at a low activity level by its C
      terminal domain, the inhibitory function of which is thought to be mediated by
      two regions (region I and II) interacting with cytoplasmic domains essential for
      the catalytic cycle. The activity of the enzyme is well known to be regulated by
      14-3-3 proteins, the association of which requires phosphorylation of the
      penultimate H(+)-ATPase residue, but can be abolished by phosphorylation of
      residues close-by. The current knowledge about H(+)-ATPase regulation is briefly
      summed up here, combined with data that query some of the above statements.
      Expression of various C-terminal deletion constructs of PMA2, a H(+)-ATPase
      isoform from Nicotiana plumbaginifolia, in yeast indicates that three regions,
      which do not correspond to regions I or II, contribute to autoinhibition. Their
      individual and combined action can be abolished by (mimicking) phosphorylation of
      three threonine residues located within or close to these regions. With respect
      to the wild-type PMA2, mimicking phosphorylation of two of these residues
      increases enzyme activity. However, constitutive activation of wild-type PMA2
      requires 14-3-3 association. Altogether, the data suggest that regulation of the
      plant H(+)-ATPase occurs in progressive steps, mediated by several protein
      kinases and phosphatases, thus allowing gradual as well as fine-tuned adjustment
      of its activity. Moreover, mating-based split ubiquitin assays indicate a complex
      interplay between the C-terminal domain and the rest of the enzyme. Notably,
      their tight contact does not seem to be the cause of the inactive state of the
      enzyme.

PMID- 20034702
TI  - The effect of radiosurgery on cochlear implant function.
AB  - Cochlear implants are used worldwide for the treatment of severe to profound
      bilateral sensorineural hearing loss in both adults and children. A number of
      implantees are likely to be treated with radiosurgery later in life, but very
      little is known about the effects of radiosurgery on cochlear implants. We report
      a cochlear-implanted patient who underwent radiosurgery due to a recurrent
      meningioma. After radiosurgery, the impedance of the implant maintained a normal
      range, and auditory performance tests were unchanged as compared to before
      radiosurgery. This is the first report addressing the effects of radiosurgery in
      a patient with a cochlear implant.

PMID- 20034703
TI  - Motherhood alters the cellular response to estrogens in the hippocampus later in
      life.
AB  - Although controversial, estrogen replacement therapy has been implicated as a
      possible therapeutic agent for ameliorating age-related cognitive decline in
      postmenopausal women. We have shown previously that different types of estrogen
      promote hippocampal neurogenesis in a dose-dependent manner in young adult female
      rats. However, previous studies have not found a beneficial effect of 17beta
      estradiol in middle-aged female rats. The aim of the present study was to
      determine the acute effects of 17beta-estradiol, 17alpha-estradiol, and estrone
      on hippocampal cell proliferation in middle-aged ovariectomized female rats and
      to determine whether effects are dependent on previous reproductive experience.
      Middle-aged multiparous female rats or age-matched virgin female rats were
      injected subcutaneously with vehicle or 10 MUg dose of 17beta-estradiol, 17alpha
      estradiol, or estrone, and then given BrdU 30 min later and perfused 24h later to
      assess cell proliferation. All estrogens significantly upregulated cell
      proliferation in the hippocampus in middle-aged multiparous females but none of
      the estrogens upregulated cell proliferation in the middle-aged virgins.
      Therefore, previous reproductive experience may make the older brain more
      responsive to estrogens later in life. We also found that 17alpha-estradiol
      upregulated cell proliferation to a greater degree than the other estrogens in
      the multiparous females. Together these findings may lead to the development of
      new therapeutic advances in the treatment of symptoms associated with menopause
      in women.

PMID- 20034704
TI  - Mutational analysis of parkin and PINK1 in multiple system atrophy.
AB  - Multiple system atrophy (MSA) and Parkinson's disease (PD) are progressive
      neurodegenerative disorders with overlapping clinical, biochemical and genetic
      features. To test the hypothesis that the PD genes parkin and PINK1 also play a
      role in the pathogenesis of MSA, we performed a mutational screening study
      involving 87 pathologically proven MSA cases. In parkin we identified eight
      sequence variants and four heterozygous deletions and in PINK1 we identified nine
      variants of which two silent mutations have not been previously reported
      (p.Gly189Gly and p.Arg337Arg). The frequencies of the observed variants were not
      significantly different from previously published control data and none of the
      possibly pathogenic variants were found in a homozygous state. Our results
      indicate that genetic variants at the parkin and PINK1 loci do not play a
      critical role in the pathogenesis of MSA.

PMID- 20034705
TI  - [Dendritic cells in sepsis: an approach to post-infectious immunosuppression].
AB  - Dendritic cells (DCs) play a decisive role in the immune system, especially in
      the initial events that determine coordination between the innate and adaptive
      response. Moreover, they are antigen-presenting cells which, through contact with
      T cells, determine the type of immune responses towards inflammatory or anti
      inflammatory. Currently, the hypothesis that attributes importance to the
      development of a post-infectious immunosuppression in the prognosis of the septic
      patient is growing stronger. It has been possible to verify the role played by
      these cells in this type of immunosuppression by the significant decrease in the
      number of DCs and by the dysfunctions in the functional capacity that include, on
      the one hand, the abnormal cytokine production and, on the other hand, the
      alterations in communication between the DCs and T cells that constitute an
      essential immunological fact. Further research into the knowledge regarding the
      DCs, in the context of severe infection, may help to consolidate some encouraging
      data that indicate these cells as: 1) an effective tool for monitoring the acute
      infection, 2) a discriminatory variable that may help determine the risk of
      nosocomial infection and 3) in a longer term, a treatment target that would
      restore the immunological abnormalities that occur in sepsis.

PMID- 20034706
TI  - New 14-membered octaazamacrocyclic complexes: synthesis, spectral, antibacterial
      and antifungal studies.
AB  - A novel series of macrocyclic complexes of the type [M(C(18)H(14)N(10)S(2))X]X(2)
      where M=Cr(III), Fe(III) and Mn(III); X=Cl(-), NO(3)(-) and CH(3)COO(-) have been
      synthesized by [2+2] condensation of thiocarbohydrazide and isatin in the
      presence of trivalent metal salts in methanolic medium by template method. The
      complexes have been characterized with the help of elemental analyses,
      conductance measurements, magnetic measurements, electronic, NMR, IR and mass
      spectral studies. On the basis of these studies, a five coordinate square
      pyramidal geometry for all of these complexes has been proposed. These metal
      complexes were also tested for their in vitro antimicrobial activities against
      some bacterial strains viz. Staphylococcus aureus, Bacillus subtilis, Escherichia
      coli, Pseudomonas aeruginosa and some fungal strains Aspergillus niger,
      Aspergillus flavus (molds), Candida albicans, Saccharomyces cerevisiae (yeasts).

PMID- 20034707
TI  - Design, synthesis and pharmacological screening of potential anticonvulsant
      agents using hybrid approach.
AB  - A series of 9H, 10H, 3-[N- 4 methyl -2-benzamido thiophen 3-yl carbonyl amino [2
      (2'-phenyl 1'- ethylenyl)] 10-(aryl) thiazolidino [4, 5-b] 1, 5 benzodiazepine
      [7a-7h] were designed and synthesized to meet the structural requirements
      essential for anticonvulsant activity. Anticonvulsant activity was determined
      after intra-peritoneal administration to mice by supramaximal electroshock
      seizures model and Isoniazide Hydrazone induced seizures model. Motor impairement
      was determined using actophotometer and rotarod apparatus. Among the synthesized
      compounds two [JG 7a and JG 7e] compounds exhibited significant anticonvulsant
      activity after intra-peritoneal administration. Active compounds carry hydroxy
      substitutent at 2-position and methoxy at 4-position in the phenyl ring at C(5)
      of benzodiazepine. In present we study conclude that small polar and electron
      rich groups contribute significantly for anticonvulsant activity while
      electronegative substitutents showed lesser contribution for anticonvulsant
      activity.

PMID- 20034708
TI  - New 1,3-oxazolo[4,5-c]quinoline derivatives: synthesis and evaluation of
      antibacterial and antituberculosis properties.
AB  - A new class of fused oxazoloquinoline derivatives was synthesized starting from 2
      bromo-1-phenylethanones 1a-b through multi-step reactions. The newly synthesized
      compounds were evaluated for their in vitro antibacterial against Escherichia
      coli (ATTC-25922), Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa
      (ATCC-27853) and Klebsiella pneumoniae (recultured) and antituberculosis activity
      against Mycobacterium tuberculosis H37Rv (ATCC 27294). Preliminary results
      indicated that most of the compounds demonstrated very good antibacterial and
      antituberculosis activities which are comparable with the first line drugs.
      Compounds 6a, 6c, 6g, 6j, 6k and 6n emerged as the lead antitubercular agents
      with MIC, 1 microg/mL and 99% bacterial inhibition while eight compounds, viz.,
      5a, 15k, 6a, 6c, 6g, 6j, 6k and 6n were found to be more potent than INH (MIC:
      1.5 microg/mL) with MIC 1 microg/mL.

PMID- 20034709
TI  - Synthesis and antioxidant properties of enone core based dendrimers with
      carbazole as surface group.
AB  - Synthesis of enone core based dendrimers with carbazole as surface group has been
      achieved. All the synthesized dendrimers showed excellent antioxidant behavior
      with commercially available 1,1-diphenyl-2-picryl hydrazyl (DPPH).

PMID- 20034710
TI  - Simultaneous tritium labelling of two potent 5-HT4 ligands.
AB  - Two potent and selective 5-HT(4) ligands, [(3)H]-5-[(N-propylpiperidin-4
      yl)methoxy]-1,2,3,4-tetrahydrobenzo[h][1,6] naphthyridine (1a) and [(3)H]-1
      methyl-5-[(N-propylpiperidin-4-yl)methoxy]pyrrolo[1,2-a]thieno[2,3-e]pyrazine
      (2a) were radiolabelled with tritium. Radioactive labelling was achieved by
      simultaneous tritium reduction of a mixture of both propargylic precursors (1c
      2c). The two tritiated ligands thus obtained were radiochemically pure and
      possessed high radioactive specific activities. These tritiated 5-HT(4) ligands
      will allow for binding characterization as an essential tool for their further
      development.

PMID- 20034711
TI  - Synthesis, antibacterial and antiviral properties of curcumin bioconjugates
      bearing dipeptide, fatty acids and folic acid.
AB  - Curcumin bioconjugates, viz. di-O-tryptophanylphenylalanine curcumin (2), di-O
      decanoyl curcumin (3), di-O-pamitoyl curcumin (4), di-O-bis-(gamma,gamma)folyl
      curcumin (6), C(4)-ethyl-O-gamma-folyl curcumin (8) and 4-O-ethyl-O-gamma-folyl
      curcumin (10) have been synthesized and tested for their antibacterial and
      antiviral activities. The conjugates 2, 3, 4, 6 and 8 have shown very promising
      antibacterial activity with MIC ranging between 0.09 and 0.67 microM against Gram
      positive cocci and Gram-negative bacilli. Further, the conjugates 2, 3, 6, 8 and
      10 have been screened for their antiviral activities against HSV, VSV, FIPV, PIV
      3, RSV and FHV and the molecules 2 and 3 have shown good results with EC(50)
      0.011 microM and 0.029 microM against VSV and FIPV/FHV, respectively. However,
      the molecules did not show expected results against HIV-1 III(B) and ROD strains
      in MTT assay.

PMID- 20034712
TI  - 2-Butoxyethanol model of haemolysis and disseminated thrombosis in female rats: a
      preliminary study of the vascular mechanism of osteoarthritis in the
      temporomandibular joint.
AB  - Female rats develop haemolytic anaemia and disseminated thrombosis and infarction
      in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There
      is growing evidence that vascular occlusion of the subchondral bone may play a
      part in some cases of osteoarthritis. The subchondral bone is the main weight
      bearer as well as the source of the blood supply to the mandibular articular
      cartilage. Vascular occlusion is thought to be linked to sclerosis of the
      subchondral bone associated with disintegration of the articular cartilage. The
      aim of this study was to find out whether this model of haemolysis and
      disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six
      female rats were given BE orally for 4 consecutive days and the two control rats
      were given tap water alone. The rats were killed 26 days after the final dose.
      The mandibular condyles showed histological and radiological features consistent
      with osteoarthritis in three of the four experimental rats and in neither of the
      control rats. These results may support the need to explore the vascular
      mechanism of osteoarthritis further.

PMID- 20034713
TI  - Effect of wrist position on thumb flexor and adductor torques in paralysed hands
      of people with tetraplegia.
AB  - BACKGROUND: People with tetraplegia often have extensive paralysis of the hand
      yet retain crude hand function. Their hand function is dependent on manipulating
      wrist position with the neurally-intact wrist extensor muscles to change the
      passive tension in paralysed thumb muscles. This moves the thumb in relation to
      the paralysed index finger enabling basic grasp. The aim of this study was to
      quantify the effect of wrist position on thumb flexor and adductor torques
      generated in paralysed hands of people with tetraplegia. METHODS: Thumb flexor
      and adductor torques were measured as the wrist was passively moved from a fully
      flexed to a fully extended position in 10 people with tetraplegia who had
      paralysis of all thumb muscles. The relationships between thumb torques and wrist
      angles were quantified with torque-angle curves. FINDINGS: There was a consistent
      curvilinear relationship between wrist angle and both thumb flexor and thumb
      adductor torques. Thumb flexor torques were greatest and thumb adductor torques
      were smallest when the wrist was fully extended. INTERPRETATION: Wrist position
      influences the thumb flexor and adductor torques generated in the paralysed hand.
      This is probably due to the effect of wrist position on the passive tension of
      the thumb muscles spanning the wrist. These findings have implications for people
      with C6 and C7 tetraplegia who rely on the passive torques generated by the
      paralysed thumb muscles for hand function.

PMID- 20034714
TI  - Chemical contamination and the ecological quality of surface water.
AB  - In the assessment of the quality of surface waters, the typical procedure is that
      the concentration of contaminants in the surface water is monitored and
      subsequently compared with their respective Maximum Permissible Concentrations
      (MPCs). If the MPCs are not exceeded the water quality is considered to be safe.
      But can we be certain that this is true? We compared MPCs to observed and
      calculated effects of measured contaminants in Dutch surface waters and showed
      that effects of mixtures can cause a daphnid population to go extinct within 30h
      of exposure even when MPCs are not exceeded. We conclude that there are
      shortcomings underlying the concepts of the MPCs. And that the MPCs aim to
      protect 95% of all species is not met.

PMID- 20034715
TI  - Effects of low concentration biodiesel blends application on modern passenger
      cars. Part 2: impact on carbonyl compound emissions.
AB  - Today in most European member states diesel contains up to 5% vol biodiesel.
      Since blending is expected to increase to 10% vol, the question arises, how this
      higher mixing ratio will affect tailpipe emissions particularly those linked to
      adverse health effects. This paper focuses on the impact of biodiesel on carbonyl
      compound emissions, attempting also to identify possible relationship between
      biodiesel feedstock and emissions. The blends were produced from five different
      feedstocks, commonly used in Europe. Measurements were conducted on a Euro 3
      common-rail passenger car over various driving cycles. Results indicate that
      generally the use of biodiesel at low concentrations has a minor effect on
      carbonyl compound emissions. However, certain biodiesels resulted in significant
      increases while others led to decreases. Biodiesels associated with increases
      were those derived from rapeseed oil (approx. 200%) and palm oil (approx. 180%),
      with the highest average increases observed at formaldehyde and
      acroleine/acetone.

PMID- 20034716
TI  - Relationship between heavy metals pollution and genetic diversity in
      Mediterranean populations of the sandhopper Talitrus saltator (Montagu)
      (Crustacea, Amphipoda).
AB  - Trace metals are one of the groups of pollutants that reduce genetic variability
      in natural populations, causing the phenomenon known as "genetic erosion". In
      this study we evaluate the relationship between trace metals contamination (Hg,
      Cd and Cu) and genetic variability, assessed using fluorescent Inter-Simple
      Sequence Repeats (fISSRs). We used eight populations of a well-established
      biomonitor of trace metals on sandy beaches: the amphipod Talitrus saltator. The
      trace metals analysis confirmed the ability of sandhoppers to accumulate Hg, Cd
      and Cu. Moreover, populations from sites with high Hg availability had the lowest
      values of genetic diversity. Our results validate the use of fISSR markers in
      genetic studies in sandhoppers and support the "genetic erosion" hypothesis by
      showing the negative influence of Hg contamination on sandhopper genetic
      diversity. Therefore, genetic variability assessed with fISSR markers could be
      successfully employed as a biomarker of Hg exposure.

PMID- 20034717
TI  - Differences in EDTA-assisted metal phytoextraction between metallicolous and non
      metallicolous accessions of Rumex acetosa L.
AB  - Two common sorrel (Rumex acetosa) accessions, one from a Zn-Pb contaminated site
      (CS accession) and the other from an uncontaminated site (UCS accession), were
      hydroponically exposed to a mixture of heavy metals (Pb(2+) + Zn(2+) + Cd(2+))
      with and without EDTA at an equimolar rate. The metallicolous CS accession showed
      a higher tolerance to metal treatment in the absence of the chelating agent,
      whereas the UCS accession was especially tolerant to EDTA treatment alone.
      Combination of metal and EDTA treatment resulted in a higher Pb accumulation in
      shoots of both accessions although plants hardly showed phytotoxic symptoms. Cd
      and Zn uptake was not augmented by EDTA addition to the polymetallic medium.
      Chelant-assisted Pb accumulation was 70% higher in the CS accession than in the
      UCS accession, despite the fact that the former accession evapotranspired less
      water than the UCS accession. These results support the existence of a non
      selective apoplastic transport of metal chelates by R. acetosa roots, not related
      to transpiration stream.

PMID- 20034718
TI  - Preface to the special section of the IUFRO conference on air pollution and
      climate change effects on forest ecosystems.

PMID- 20034719
TI  - Sleep and fatigue symptoms in children and adolescents with CKD: a cross
      sectional analysis from the chronic kidney disease in children (CKiD) study.
AB  - BACKGROUND: Although symptoms of sleepiness and fatigue are common in adults with
      chronic kidney disease (CKD), little is known about the prevalence of these
      symptoms in children with CKD. STUDY DESIGN: Cross-sectional analysis within a
      cohort study. SETTING & PARTICIPANTS: We describe the frequency and severity of
      sleep problems and fatigue and assess the extent of their association with
      measured glomerular filtration rate (mGFR) and health-related quality of life
      (HRQOL) in 301 participants of the Chronic Kidney Disease in Children cohort.
      OUTCOMES & MEASUREMENTS: Sleep and fatigue-related items from the Pediatric
      Quality of Life Inventory 4.0 Generic Scales and the CKD-related Symptoms List
      were used. RESULTS: Median mGFR was 42.0 mL/min/1.73 m(2) (25th-75th percentiles,
      31.2-53.2), and median age was 13.9 years (25th-75th percentiles, 10.8-16.2).
      Children with mGFR of 40-<50, 30-<40, or <30 mL/min/1.73 m(2) had 2.07 (95% CI,
      1.05-4.09), 2.35 (95% CI, 1.17-4.72), and 2.59 (95% CI, 1.15-5.85) higher odds of
      having more severe parent reports of low energy than children with mGFR > or = 50
      mL/min/1.73 m(2). Compared with participants with mGFR > or = 50 mL/min/1.73
      m(2), those with mGFR < 30 mL/min/1.73 m(2) had 3.92 (95% CI, 1.37-11.17) higher
      odds of reporting more severe weakness, and those with mGFR of 40-<50 mL/min/1.73
      m(2) had 2.95 (95% CI, 1.26-6.88) higher odds of falling asleep during the day.
      Low energy, trouble sleeping, and weakness were associated with lower HRQOL
      scores. LIMITATIONS: Symptoms of sleep and fatigue represent the child's or
      parent's perception of symptom severity, whereas individual items can lead to
      imprecise measurements of sleep and fatigue. CONCLUSIONS: Lower mGFR was
      associated with increased weakness, low energy, and daytime sleepiness.
      Furthermore, a strong association between trouble sleeping, low energy, and
      weakness with decreases in overall HRQOL was observed. Detection and treatment of
      poor sleep and fatigue may improve the development and HRQOL of children and
      adolescents with CKD.

PMID- 20034720
TI  - Continuing bonds in adaptation to bereavement: Toward theoretical integration.
AB  - There is lack of clarity in the scientific literature concerning the adaptive
      functions of continuing versus relinquishing bonds to deceased persons. It
      remains unclear what type of bonds or underlying processes are related to
      (mal)adaptive bereavement outcomes. Furthermore, empirical research has rarely
      been theoretically-driven. Thus, the purpose of this article is to outline a
      theoretical model for predicting the (mal)adaptiveness of continuing
      relinquishing bonds. Attachment theory provides a generic framework for
      understanding patterns of individual differences in the impact of continuing
      bonds. Within this framework, using bereavement-specific models compatible with
      attachment theory, (1) ways of coping with the bond to the deceased can be linked
      to outcome (using the Dual Process Model, Stroebe & Schut, 1999), and (2) related
      cognitions about the deceased person proposed (drawing on Mental Representations
      Theory, Boerner & Heckhausen, 2003). This integrative model can be used to
      systematically examine the relationship between continuing bonds and bereavement
      adaptation.

PMID- 20034721
TI  - Motor adaptation and manual transfer: insight into the persistent nature of
      sensorimotor representations.
AB  - It is well known that sensorimotor memories are built and updated through
      experience with objects. These representations are useful to anticipatory and
      feedforward control processes that preset grip and load forces during lifting.
      When individuals lift objects with qualities that are not congruent with their
      memory-derived expectations, feedback processes adjust motor plans to achieve
      successful lifts and contribute to the updating of the stored representations.
      The two experiments presented examine motor adaptation to an illusory size-weight
      lifting task, and the transfer of this motor adaptation to the unexposed hand. In
      Experiment 1, performers acquired motor adaptation with their right hand and
      transfer was measured on their left hand. In Experiment 2, adaptation was
      acquired with the left hand and transfer was measured on the right hand. In order
      to investigate the persistence of sensorimotor memories, these experiments
      measure adaptation, retention, and transfer after 15min and 24h delay periods.
      Both experiments confirm that experience with objects leads to adaptation of
      force scaling processes, that these adaptations transcend effector and are
      persistent. The results are discussed in terms favouring interpretations that
      describe motor adaptations to illusion as being centrally available.

PMID- 20034722
TI  - [Liver growth factor improves pulmonary fibrosis secondary to cadmium
      administration in rats].
AB  - INTRODUCTION: Liver growth factor (LGF) is a liver mitogen with regenerating and
      anti-fibrotic activity even at extrahepatic sites. We used LGF in a lung fibrosis
      model induced by cadmium chloride (CdCl(2)), to study its antifibrotic capacity.
      METHODS: Forty-two male Wistar rats were administered a single dose of 0.5ml/rat
      of CdCl2 0.025% (n=21) or the same volume of saline (control group, n=21). After
      35 days, once a lesion was established, we started a 3 week treatment with LGF,
      after which we determined lung function--inspiratory capacity (IC), lung
      compliance (LC), forced vital capacity (FVC) and expiratory flow at 75% (FEF75%)
      , lung morphometry--alveolar internal area (AIA), mean linear intersection (LM)-,
      and collagen (both by Sirius red and hydroxyproline residues) and elastin
      contents. RESULTS: Pulmonary fibrosis in CdCl(2) rats was characterized by a
      marked decrease in pulmonary function with respect to healthy controls 
      reductions of 28% in IC, 38% in CL, 31% in FVC, and 54% in FEF75%- which was
      partially recovered after LGF injection -18% IC, 27% CL, 19% FVC and 35% FEF75%-;
      increase in collagen and elastin contents -165% and 76%, respectively, in CdCl2
      rats, versus 110% and 34% after LGF injection-; and increases in AIA and LM,
      partially reverted by LGF. CONCLUSIONS: Together, these data seem to demonstrate
      that LGF is able to improve lung function and partially reverts the increase in
      lung matrix proteins produced by CdCl(2) instillation.

PMID- 20034723
TI  - The importance of in vitro component-resolved diagnosis in paediatric patients.
AB  - In recent years, thanks to advances in molecular biology, allergological
      diagnosis has improved and specific IgE (sIgE) against an allergenic source has
      been transformed into sIgE against an allergenic protein or glycoprotein. This
      change, which has resulted in a more precise diagnosis of sensitisation, could
      explain the different dangers of certain molecular sensitisations and in many
      cases cross-reactivity phenomena, and could change indications for immunotherapy
      or clinical management. Here, we present two cases of children where the
      indication for immunotherapy and management of the disorder changed due to
      component-resolved diagnosis. However, the clinical history and skin prick tests
      should complement molecular in vitro diagnosis to improve routine clinical
      practice.

PMID- 20034724
TI  - Sildenafil citrate improves fetal outcomes in pregnant, L-NAME treated, Sprague
      Dawley rats.
AB  - OBJECTIVES: This study aimed to investigate the effects of sildenafil citrate on
      various fetal and physiological parameters, including fetal mortality, number of
      pups, placental weights and micro-albuminuria in pregnant, L-NAME treated Sprague
      Dawley rats. STUDY DESIGN: Twenty-four pregnant female Sprague-Dawley rats were
      divided into 3 groups (n=8). In the L-NAME treated group (PRE), l-NAME (0.3 g/l,
      drinking water) was used to induce pre-eclampsia-like symptoms on day 1 of the
      experiment. The experimental group (SCT) also received L-NAME (0.3 g/l, drinking
      water) on day 1 of the experiment. However, sildenafil citrate (10 mg/kg, s.c.,
      daily) was administered as the test compound from day 7 until day 19. The
      experimental control (CON) did not receive either L-NAME or sildenafil citrate. L
      NAME administration was discontinued in both the PRE and the SCT groups on day 19
      of the experiment and the animals were given access to normal drinking water ad
      libitum. All the animals were sacrificed on day 20, at which time a laparotomy
      was performed and the various fetal parameters measured. On day 0 and day 20,
      blood pressure measurements were recorded non-invasively and protein estimations
      in 24h urine samples were conducted. RESULTS: Sildenafil citrate decreased fetal
      mortality and protein excretion and further demonstrated a trend toward
      increasing birth and placental weights in pregnant, L-NAME treated, Sprague
      Dawley rats. In addition, sildenafil citrate administration ameliorated the
      amplification of the L-NAME induced hypertension in the SCT group. CONCLUSION: We
      speculate that sildenafil citrate by potentiating the effects of nitric oxide in
      vivo improves uterine artery blood flow resulting in improved fetal outcomes in
      pregnant, L-NAME treated, Sprague-Dawley rats.

PMID- 20034725
TI  - Using multi-objective computational design to extend protein promiscuity.
AB  - Many enzymes possess, besides their native function, additional promiscuous
      activities. Proteins with several activities (multipurpose catalysts) may have a
      wide range of biotechnological and biomedical applications. Natural promiscuity,
      however, appears to be of limited scope in this context, because the latent
      (promiscuous) function is often related to the evolved one (sharing the active
      site and even the chemical mechanism) and its enhancement upon suitable mutations
      usually brings about a decrease in the native activity. Here we explore the use
      of computational protein design to overcome these limitations. The high
      plasticity positions close to the original ("native") active-site are the most
      promising candidates for mutations that create a second active-site associated to
      a new function. To avoid compromising protein folding and native activity, we
      propose a minimal-perturbation approach based on the combinatorial optimization
      of, both the de novo catalytic activity and the folding free-energy: essentially,
      we construct the Pareto Set of optimal stability/promiscuous-function solutions.
      We validate our approach by introducing a promiscuous esterase activity in E.
      coli thioredoxin on the basis of mutations at positions close to the native
      active-site disulfide-bridge. Native oxidoreductase activity is not compromised
      and it is, in fact, found to be 1.5-fold enhanced, as determined by an insulin
      reduction assay. This work provides general guidelines as to how computational
      design can be used to expand the scope and applications of protein promiscuity.
      From a more general viewpoint, it illustrates the potential of multi-objective
      optimization as the computational analogue of multi-feature natural selection.

PMID- 20034726
TI  - Expressing Hoxa2 across the entire endochondral skeleton alters the shape of the
      skeletal template in a spatially restricted fashion.
AB  - Hox genes control morphogenesis along the antero-posterior axis. The skeleton of
      vertebrates offers an exemplar readout of their activity: Hox genes control the
      morphology of the skeleton by defining type of vertebrae, and structure of the
      limbs. The head skeleton of vertebrates is formed by cranial neural crest (CNC),
      and mainly by a Hox-free domain of the CNC. Ectopic expression of anterior Hox
      genes in the CNC prevents the formation of the facial skeleton. These inhibitory
      effects on skeletogenesis are at odds with the recognized function of Hox genes
      in patterning the developing skeleton. To clarify these controversial effects, we
      overexpressed Hoxa2 across the entire developing endochondral skeleton in mouse.
      This gave rise to strong and spatially restricted effects: the most noticeable
      abnormalities were detected in the cranial base and consisted in a failure of
      bones to form or in a transformed morphology of bones. The rest of the skeleton
      exhibited milder defects, which never consisted in the absence or the
      transformation of any skeletal components. Analyses at early stages of
      endochondral bone development showed disorganized cell condensations in the
      cranial base of Col2a1-Hoxa2 transgenic embryos. We show that the distribution of
      Hoxa2-positive cells in Col2a1-Hoxa2 embryos does not match the wild-type
      developing cartilages. The Hoxa2-positive cells detected in atypical, non
      chondrogenic location in the cranial base, remain as chondrocytes and lay down
      cartilage, indicating that Hoxa2 does not alter the fate of chondrocytes, but
      interferes with their spatial distribution. We propose that the ability of Hoxa2
      to change the spatial distribution of cells accounts for the different phenotypes
      observed in Col2a1-Hoxa2 embryos; it also provides an explanation for the
      apparent inconsistency between the inhibitory effects of Hoxa2 on skeletal
      development, and the ability of Hox genes to establish the morphology of the
      vertebrate skeleton.

PMID- 20034727
TI  - Dynamic sorption of ammonium by sandy soil in fixed bed columns: Evaluation of
      equilibrium and non-equilibrium transport processes.
AB  - The release of excess nitrogen-containing compounds into groundwater is a major
      concern in aquifer recharge by the Soil Aquifer Treatment (SAT) process. Ammonium
      (NH(4)(+)) is one of the most nocive and common nitrogen compounds in
      wastewaters. In order to assess the risk of wastewater use for aquifer recharge,
      NH(4)(+)adsorption onto Souhil wadi soil sampled from the SAT pilot plant
      (Nabeul, Tunisia) was studied using laboratory columns experiments. Several
      experiments were conducted using aqueous synthetic solutions under different
      aqueous ammonium concentrations and flow rates. Furthermore, a real wastewater
      solution was used to test the effect of competitive cations contents on NH(4)(+)
      adsorption. Afterwards, the Hydrus-1D model was used in inverse mode to simulate
      the ammonium transport through the Souhil wadi soil. For the synthetic solutions,
      the adsorbed ammonium amount varied from 1 to 30.7 mg kg(-1) for aqueous ammonium
      concentrations between 4.9 and 36.4 mg L(-1). The linear isotherm model was found
      to be the most suitable for describing this adsorption. The flow rate decrease
      from 45 to 15 mL min(-1) induced an increase in the ammonium adsorption capacity
      by 49%. Indeed, the lesser the flow rate is, the longer the residence time and
      the higher the exchange between the aqueous solution and soil matrix. The use of
      wastewater instead of aqueous synthetic solution decreased about 7 times the
      Souhil wadi adsorption capacity of ammonium because of its relatively high
      concentrations of competitive ions such as calcium and magnesium. The use of the
      Hydrus-1D model showed that the chemical non-equilibrium model was the best to
      simulate the ammonium transport through the laboratory soil columns.

PMID- 20034728
TI  - Performance of newly implemented Environmental Management Systems in primary
      schools in South Africa.
AB  - Quantitative results from Environmental Management Systems (EMS) at primary
      schools have rarely been examined in literature. This paper presents the
      monitoring results of environmental care in 39 primary schools in Northern South
      Africa. During 2 years, after the EMS was implemented in the curriculum and in
      the school's management, the progress of environmental performances of the
      participating schools has been measured, by means of detailed questionnaires,
      related to four environmental aspects: water, waste, energy and greening. At the
      beginning of the project, 50% of the schools performed well on water-related
      environmental actions. Two years later it was 76%. For waste-related activities
      the improvement was even stronger: from 50% to 100%. The environmental
      performances of the schools improved also for greening-related actions, from 50%
      at the start of the project to 64% two years later. Only energy-related
      activities did not improve significantly with only 24% of all schools performing
      well at the end of the survey period. In general, the introduction of an EMS
      succeeded in an improvement of the overall environmental performances of the
      schools, but cost-intensive activities were less successful than others.

PMID- 20034729
TI  - Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study
      30911 comparing intravesical instillations of epirubicin, bacillus Calmette
      Guerin, and bacillus Calmette-Guerin plus isoniazid in patients with intermediate
      and high-risk stage Ta T1 urothelial carcinoma of the bladder.
AB  - BACKGROUND: Intravesical chemotherapy and bacillus Calmette-Guerin (BCG) reduce
      the recurrence rate in patients with stage Ta T1 urothelial bladder cancer;
      however, the benefit of BCG relative to chemotherapy for long-term end points is
      controversial, especially in intermediate-risk patients. OBJECTIVE: The aim of
      the study was to compare the long-term efficacy of BCG and epirubicin. DESIGN,
      SETTING, AND PARTICIPANTS: From January 1992 to February 1997, 957 patients with
      intermediate- or high-risk stage Ta T1 urothelial bladder cancer were randomized
      after transurethral resection to one of three treatment groups in the European
      Organization for Research and Treatment of Cancer Genito-Urinary Group phase 3
      trial 30911. INTERVENTION: Patients received six weekly instillations of
      epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance
      instillations at months 3, 6, 12, 18, 24, 30, and 36. MEASUREMENTS: End points
      were time to recurrence, progression, distant metastases, overall survival, and
      disease-specific survival. RESULTS AND LIMITATIONS: With 837 eligible patients
      and a median follow-up of 9.2 yr, time to first recurrence (p<0.001), distant
      metastases (p=0.046), overall survival (p=0.023), and disease-specific survival
      (p=0.026) were significantly longer in the two BCG arms combined as compared with
      epirubicin; however, there was no difference for progression. Three hundred
      twenty-three patients with stage T1 or grade 3 tumors were high risk, and the
      remaining 497 patients were intermediate risk. The observed treatment benefit was
      at least as large, if not larger, in the intermediate-risk patients compared with
      the high-risk patients. CONCLUSIONS: In patients with intermediate- and high-risk
      stage Ta and T1 urothelial bladder cancer, intravesical BCG with or without INH
      is superior to intravesical epirubicin not only for time to first recurrence but
      also for time to distant metastases, overall survival, and disease-specific
      survival. The benefit of BCG is not limited to just high-risk patients;
      intermediate-risk patients also benefit from BCG. TRIAL REGISTRATION: This study
      was registered with the US National Cancer Institute clinical trials database
      [protocol ID: EORTC-30911].
      http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=77075&version=HealthPr
      fessional&protocolsearchid=6540260.

PMID- 20034730
TI  - When to perform bone scan in patients with newly diagnosed prostate cancer:
      external validation of the currently available guidelines and proposal of a novel
      risk stratification tool.
AB  - BACKGROUND: Several guidelines have indicated that in patients with well
      differentiated or moderately well-differentiated prostate cancer (PCa), a staging
      bone scan may be omitted. However, the guidelines recommendations have not yet
      been externally validated. OBJECTIVE: The aim of the study was to externally
      validate the available guidelines regarding the need for a staging bone scan in
      patients with newly diagnosed PCa. Moreover, we developed a novel risk
      stratification tool aimed at improving the accuracy of these guidelines. DESIGN,
      SETTING, AND PARTICIPANTS: The study included 853 consecutive patients diagnosed
      with PCa between January 2003 and June 2008 at a single centre. All patients
      underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis.
      MEASUREMENTS: The area under the curve (AUC) of the criteria suggested by the
      guidelines (European Association of Urology, American Urological Association,
      National Comprehensive Cancer Network, and American Joint Committee on Cancer) to
      perform a baseline bone scan was assessed and compared with the accuracy of a
      classification and regression tree (CART) including prostate-specific antigen
      (PSA), clinical stage, and biopsy Gleason sum as covariates. RESULTS AND
      LIMITATIONS: The AUC of the guidelines ranged between 79.7% and 82.6%. However,
      the novel CART model, which stratified patients into low risk (biopsy Gleason
      <=7, cT1-T3, and PSA <10 ng/ml), intermediate risk (biopsy Gleason <=7, cT2/T3,
      and PSA >10 ng/ml), and high risk (biopsy Gleason >7) was significantly more
      accurate (AUC: 88.0%) than all the guidelines (all p<=0.002). The limitation of
      this study resides in its retrospective design. Moreover, the proposed risk
      stratification tool can be considered only for patients who are candidates for
      radical prostatectomy until validated in other clinical settings. CONCLUSIONS:
      This is the first study aimed at externally validating the available guidelines
      addressing the need for staging baseline bone scans in PCa patients. All
      guidelines showed high accuracy. However, their accuracy was significantly lower
      compared with the accuracy of the novel risk stratification tool. According to
      this tool, staging bone scans might be considered only for patients with a biopsy
      Gleason score >7 or with a PSA >10 ng/ml and palpable disease (cT2/T3) prior to
      treatment. However, before recommending its use in clinical practice, our model
      needs to be externally validated.

PMID- 20034731
TI  - TrueFISP imaging of the pineal gland: more cysts and more abnormalities.
AB  - INTRODUCTION: Although pineal cysts are found with a frequency of over one third
      in autopsy series, prevalences reported in standard magnetic resonance imaging
      (MRI) studies only range between 0.14% and 4.9%. With the advances in scanner
      technology and more sensitive high-resolution 3D-sequences, pineal cysts with
      atypical appearance are more frequently encountered as an incidental finding. In
      order to help the radiologist and the clinician to correctly interpret these
      incidental findings and to avoid follow-up MRI or even surgical intervention, we
      analysed the frequency of typical and atypical pineal cysts using standard MRI
      sequences and a high-resolution 3D-trueFISP-sequence (true-Fast-Imaging-with
      Steady-State-Precession). METHODS: In 111 patients undergoing MRI we analysed the
      prevalence of pineal cysts in relation to gender and age, as well as the
      frequency of atypical cysts defined by thickened rim, trabeculations, or
      asymmetric form using three standard MRI-sequences (T1-SE (T1 weighted spin
      echo), T2-TSE (T2 weighted turbo spin echo), FLAIR (fluid attenuated inversion
      recovery)) and compared the diagnostic certainty of these standard sequences with
      the sensitivity of a high-resolution trueFISP MRI sequence. RESULTS: Using
      trueFISP pineal cysts were detected more frequently than in the standard
      sequences (35.1% vs. 9.0% (T1-SE), 4.5% (T2-TSE) and 9.0% (FLAIR)). Diagnostic
      uncertainty was least frequent in trueFISP. In trueFISP, 41.0% of the detected
      cysts showed one or more features of atypical cysts (standard sequences: 21.4%).
      Highest prevalence of cysts was detected in the group of 20-30-year-old patients
      and decreased with increasing age. CONCLUSION: High-resolution 3D-sequences like
      trueFISP increase the detection rate of pineal cysts to levels reported in
      autoptic series while decreasing the diagnostic uncertainty. Atypically
      configurated pineal cysts are frequently detected as an incidental finding.

PMID- 20034732
TI  - Fanconi anemia pathway heterogeneity revealed by cisplatin and oxaliplatin
      treatments.
AB  - Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia
      (FA) proteins occurs in several cancer types, including head and neck squamous
      cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive
      to DNA crosslinking agents. However, the cytotoxicity of other commonly used
      cancer therapeutics in cells with FA pathway defects remains to be defined. Here,
      we focused on the effects of cisplatin and oxaliplatin in a panel of HNSCC and
      fibroblast cell lines. We found that FANCC- and FANCD2-mutant cells were
      unexpectedly more sensitive to platinum drugs than FANCA-mutant cells, and mono
      ubiquitination of FANCD2, which is mediated by the FANCA and FANCC containing FA
      core complex was not required for platinum resistance. Interestingly, platinum
      hypersensitivity could be dissociated from mitomycin C hypersensitivity
      suggesting different underlying mechanisms. FANCD2 or RAD51 subnuclear foci were
      not useful as biomarkers of platinum hypersensitivity of FANCC/FANCD2-mutant
      cells. Our data add to an emerging body of evidence indicating that the FA
      pathway is not linear and that several protein subcomplexes with different
      functions exist. It will be important to establish biomarkers that can predict
      the sensitivity of tumors with specific FA defects to chemotherapeutic agents.

PMID- 20034733
TI  - Scalp hair and saliva as biomarkers in determination of mercury levels in Iranian
      women: amalgam as a determinant of exposure.
AB  - The aim of this study was to determine the relationship between mercury
      concentrations in saliva and hair in women with amalgam fillings and its relation
      with age and number of amalgam fillings. Eighty-two hair and saliva samples were
      collected randomly from Iranian women who have the same fish consumption pattern
      and free from occupational exposures. The mean+/-SD age of these women was
      29.37+/-8.12 (ranged from 20 to 56). The determination of Hg level in hair
      samples was carried out by the LECO, AMA 254, Advanced Mercury Analyzer according
      to ASTM, standard No. D-6722. Mercury concentration in saliva samples was
      analyzed by PERKIN-ELMER 3030 Cold Vapor Atomic Absorption Spectrophotometer. The
      mean+/-SD mercury level in the women was 1.28+/-1.38 microg/g in hair and 4.14+/
      4.08 microg/l in saliva; and there were positive correlation among them. A
      significant correlation was also observed between Hg level of saliva (Spearman's
      rho=0.93, P<0.001) and hair (Spearman's rho=0.92, P<0.001) with number of amalgam
      fillings. According to the results, we can conclude that amalgam fillings may be
      an effective source for high Hg concentration in hair and releasing the mercury
      to the saliva samples.

PMID- 20034734
TI  - Measurement and human exposure assessment of brominated flame retardants in
      household products from South China.
AB  - Brominated flame retardants (BFRs), polybrominated diphenyl ethers (PBDEs), and
      decabromodiphenyl ethane (DBDPE) were examined in household products in the Pearl
      River Delta, South China, including electronic appliances, furniture and
      upholstery, car interiors, and raw materials for electronics. The concentrations
      of PBDEs derived from penta-BDE mixture were much lower (<111 ng/g) than those
      for octa- and deca-BDE commercially derived PBDEs, with maximum values of 15,107
      and 1,603,343 ng/g, respectively, in all the household products. Our findings
      suggest the recycling of old electronic products and their reuse might be also a
      potential important source of discontinued PBDEs to the environment. DBDPE was
      found in 20.0% of all the samples, ranging from 311 to 268,230 ng/g. PBDE
      congener profiles in both the household products and raw materials suggest that
      some less brominated BDEs in the environment may be derived from the
      decomposition of higher brominated PBDEs in PBDE-containing products in process
      of the manufacturing, use and/or recycling. Human exposure to PBDEs from
      household products via inhalation ranged from 175 to 612 pg/kg bw day, accounting
      for a small proportion of the total daily exposure via indoor inhalation. Despite
      the low deleterious risk associated with household products with regard to PBDEs,
      they are of special concern because of the relatively higher exposures observed
      for young children and further work is required.

PMID- 20034735
TI  - Cloud point extraction combined with high-performance liquid chromatography for
      speciation of chromium(III) and chromium(VI) in environmental sediment samples.
AB  - A sensitive and simple method for high-performance liquid chromatography (HPLC)
      determination of traces of chromium species in lake sediments after
      preconcentration by cloud point extraction (CPE) has been developed. Simultaneous
      preconcentration of Cr(III) and Cr(VI) in sediment samples was achieved by CPE
      with 1-(2-thiazolylazo)-2-naphthol (TAN) as the chelating agent and non-ionic
      surfactant octylphenoxypolyethoxyethanol (Triton X-114) as the extractant.
      Baseline separation of the TAN chelates of Cr(III) and Cr(VI) was realized on a
      RP-C(18) column by using a mixture of methanol-water (69:31, v/v) solution and
      4.5 mmol L(-1) CTMAB buffered with 0.03 mol L(-1) NaAc-HAc solution (pH 5.5) as
      the mobile phase at a flow rate of 0.8 mL min(-1). The variables affecting the
      complexation and extraction steps were examined. The precision (R.S.D.) for seven
      replicate injections of a mixture of 100 microg L(-1) of Cr(III) and Cr(VI) was
      1.2 and 0.9% for the retention time, 4.7 and 2.7% for the peak area,
      respectively. The concentration factor was 45 for Cr(III) and 40 for Cr(VI). The
      detection limit (LOD) of this method, calculated as three times the standard
      deviation of the blank signals was 7.5 microg L(-1) for Cr(III) and 3.5 microg L(
      1) for Cr(VI), respectively. The proposed procedure was applied to the speciation
      of chromium in sediment samples with satisfactory results.

PMID- 20034736
TI  - Performance of membrane bioreactor (MBR) system with sludge Fenton oxidation
      process for minimization of excess sludge production.
AB  - The study reports the minimization of excess sludge produced in the membrane
      bioreactor (MBR) coupled with a sludge Fenton oxidation (oxidation using H(2)O(2)
      with an iron catalyst) process. Total experimental period was divided into two
      stages. At the first stage, a series of batch studies were carried out to
      elucidate the parameters governing the activated sludge disintegration. It was
      found that Fenton oxidation can disrupt the cell walls and cause the release of
      plasm from the cells, thus increasing the content of soluble organics and soluble
      nitrogen in the solution. At the following stage, two MBRs with and without the
      Fenton process were operated to evaluate the influence of sludge Fenton oxidation
      on the sludge yield and water quality. It was demonstrated that the incorporation
      of Fenton process can significantly reduce sludge production, as evidenced from
      the decrease in the value of the average sludge yield from 0.15 to 0.006 g MLSS/g
      COD. The water quality of effluent in both systems was maintained at a
      satisfactory level. Furthermore, it was revealed that the MBR system with the
      sludge Fenton oxidation process showed relatively better performance for TN
      removal than that without it.

PMID- 20034737
TI  - Oxidative degradation of dinitro butyl phenol (DNBP) utilizing hydrogen peroxide
      and solar light over a Al2O3-supported Fe(III)-5-sulfosalicylic acid (ssal)
      catalyst.
AB  - A novel and efficient photo-Fenton catalyst of Fe(III)-5-sulfosalicylic acid
      (ssal) supported on Al(2)O(3) was prepared and characterized by FT-IR and TEM-EDX
      technique. A detailed investigation of photocatalytic degradation of 2-sec-butyl
      4,6-dinitrophenol (DNBP) using this catalyst and H(2)O(2) under solar light
      irradiation was carried out. The effects of reaction parameters on
      photodegradation performance were investigated by examining H(2)O(2) dosage,
      catalyst loading, solution pH, initial DNBP concentration and temperature. The
      optimal conditions were an initial DNBP concentration of 40 mg L(-1) at pH 2.5
      and temperature 30 degrees C with catalyst loading of 1.0 g L(-1) and H(2)O(2)
      concentration of 5 mmol L(-1) under solar light irradiation for 100 min. Almost
      complete degradation of DNBP was observed with [Fe(III)-ssal]-Al(2)O(3)/H(2)O(2)
      process under the optimal conditions. The degradation of DNBP by photo-Fenton
      type process can be divided into the initiation phase and the fast phase. The
      kinetics of Fenton oxidation is complex and the degradation of DNBP in the two
      phases both can be described by a pseudo-first-order kinetic model. No obvious
      decline in efficiency of the [Fe(III)-ssal]-Al(2)O(3) catalyst was observed after
      5 repeated cycles indicating this catalyst is stable and reusable. A possible
      reaction mechanism was proposed on the basis of all the information obtained
      under various experimental conditions.

PMID- 20034738
TI  - Synthesis and explosive properties of copper(II) chlorate(VII) coordination
      polymer with 4-amino-1,2,4-triazole bridging ligand.
AB  - Copper(II) chlorate(VII) coordination polymer with 4-amino-1,2,4-triazole as
      bridging ligand was prepared and characterized by elemental analysis, IR spectra
      and TG/DTA analyses. Sensitivity and detonator tests were also preformed. The
      compound has a 1D chain structure in which Cu(II) ions are linked by triple
      triazole N1,N2 bridges. It is a detonat with performance close to that of lead
      azide, but at the same time it shows moderate sensitivity to thermal (explosively
      decomposes above 250 degrees C) and mechanical stimuli (sensitivity to friction
      10N).

PMID- 20034739
TI  - Photodegradation of oxytetracycline in aqueous by 5A and 13X loaded with TiO2
      under UV irradiation.
AB  - The photocatalysis degradation, mineralization and detoxification of
      oxytetracycline (OTC) in aqueous were investigated by 5A and 13X zeolite with
      nano-TiO(2) loaded under UV light. The composite photocatalysts are characterized
      by X-ray diffraction (XRD) and field emission scanning (FESEM) technologies. The
      adsorption isotherms of OTC by 5A and 13X with different pH are evaluated. The
      results show that 654 and 1497 mg/g OTC of saturation adsorption capacity is
      reached by 5A and 13X at pH 7, respectively. Then the effect of TiO(2) with 5A
      and 13X support and different wt% of TiO(2) over the support on the resultant OTC
      removal, net photocatalytic degradation and influence factors such as TiO(2)
      loading, initial pH, concentration of OTC and adding anion on degradation are
      investigated. The 15 wt% TiO(2)/5A and 10 wt% TiO(2)/13X photocatalysts are found
      optimum for OTC removal and degradation in aqueous. The mineralization was
      measured by total organic carbon (TOC) while combined toxicity change during OTC
      degradation was tested with standardized bioluminescence assay of inhibition rate
      on Vibrio qinghaiensis sp.-Q67 (Q67). The results suggest that TiO(2)/5A and
      TiO(2)/13X composite systems are effective photocatalysts for treatment of OTC in
      aqueous.

PMID- 20034740
TI  - Electrodialytic treatment for metal removal from sewage sludge ash from fluidized
      bed combustion.
AB  - Sewage sludge contains several potentially hazardous compounds such as heavy
      metals, PCBs, PAHs, etc. However, elements with high agricultural value (P, K or
      Ca) are also present. During the last years, the fluidized bed sludge combustor
      (FBSC) is considered an effective and novel alternative to treat sewage sludge.
      By its use, the high amount of sludge is reduced to a small quantity of ash and
      thermal destruction of toxic organic constituents is obtained. Conversely, heavy
      metals are retained in the ash. In this work the possibility for electrodialytic
      metal removal for sewage sludge ash from FBSC was studied. A detailed
      characterization of the sewage sludge ash was done initially, determining that,
      with the exception of Cd, the other heavy metals (Cr, Cu, Pb, Ni and Zn) were
      under the limiting levels of Danish legislation for the use of sewage sludge as
      fertilizer. After 14 days of electrodialytic treatment, the Cd concentration was
      reduced to values below the limiting concentration. In all experiments the
      concentrations of other metals were under limiting values of the Danish
      legislation. It can be concluded that the electrodialytic treatment is an
      adequate alternative to reduce the Cd concentration in FBSC ash prior to use as
      fertilizer.

PMID- 20034741
TI  - The effect of dissolved oxygen on the 1,4-dioxane degradation with TiO2 and Au
      TiO2 photocatalysts.
AB  - In order to enhance the photocatalytic activity of TiO(2), the recombination of
      photogenerated electron-hole pairs needs to be suppressed. Noble metals, e.g. Au
      nanoparticles, have been incorporated with TiO(2) to efficiently separate charge
      carriers created in/on TiO(2). On the other hand, dissolved oxygen (DO) in an
      aqueous solution was also known to scavenge the electrons, which avoid the
      recombination of electrons and holes. In this study, we investigated the combined
      system of Au nanoparticles incorporated with TiO(2) and DO to gain insight into
      the relationship between them using a photocatalytic degradation of 1,4-dioxane.
      The rate constants of 1,4-dioxane photodegradation with respect to TiO(2)
      catalysts with three different Au loadings, as well as DO levels, indicated the
      DO dependency is disproportional to the Au loading amount, implying that there is
      an overlapping function in capturing electrons between Au nanoparticles and DO.

PMID- 20034742
TI  - Arsenic removal from aqueous solution using ferrous based red mud sludge.
AB  - Ferrous based red mud sludge (FRS) which combined the iron-arsenic co
      precipitation and the high arsenic adsorption features was developed aimed at low
      arsenic water treatment in rural areas. Arsenic removal studies shown that FRS in
      dosage of 0.2 or 0.3g/l can be used effectively to remove arsenic from aqueous
      solutions when initial As(V) concentration was 0.2 or 0.3mg/l. Meanwhile,
      turbidity of supernatant in disturbing water was lower than 2 NTU after 24h. The
      pH range (4.5-8.0) for FRS in effective arsenic removal was applicable in natural
      circumstance. Phosphate can greatly reduce the arsenic removal efficiency while
      the presence of carbonate had no significant effect on arsenic removal. Arsenic
      fractionation experiments showed that amorphous hydrous oxide-bound arsenic was
      the major components. When aqueous pH was decreased from 8.0 to 4.5, arsenic in
      FRS was not obviously released. The high arsenic uptake capability, good
      settlement performance and cost-effective characteristic of FRS make it
      potentially attractive material for the arsenic removal in rural areas.

PMID- 20034743
TI  - Comparison of pain and dyspnea perceptual responses in healthy subjects.
AB  - Dyspnea and pain have a number of similarities. Recent brain imaging experiments
      showed that similar cortical regions are activated by the perceptions of dyspnea
      and pain. We tested the hypothesis that an individual's pain sensitivity might
      parallel the individual's dyspnea sensitivity. Studies were carried out in 52
      young healthy subjects. Each subject experienced experimentally induced pain and
      dyspnea. Pain was induced by a cold-pressor test and dyspnea was induced by
      breathholding while the unpleasant experience of pain and dyspnea was assessed by
      using a Visual Analogue Scale (VAS). The times from the start of cold stimulation
      and breathholding to the onset of uncomfortable sensation (pain threshold time
      and the period of no respiratory sensation, respectively) and to the limit of
      tolerance (pain endurance time and total breathholding time, respectively) were
      also measured. In response to cold pain stimulation, a behavioral dichotomy (pain
      tolerant and pain-sensitive) was observed. The period of no respiratory sensation
      was significantly shorter in the PS (pain-sensitive) group than in the PT (pain
      tolerant) group (16.9+/-3.8 vs. 19.6+/-5.3 s: P<0.05), whereas no significant
      difference in the total breathholding time was found between the PT and PS
      groups. A significant correlation was observed between the pain threshold time
      and the period of no respiratory sensation in both the PT and PS groups. However,
      no significant association was observed between pain and dyspnea tolerance in
      both groups. In conclusion, an individual's pain threshold is correlated to the
      individual's dyspnea threshold, but the individual's pain tolerance is not
      consistently correlated to the individual's dyspnea tolerance.

PMID- 20034745
TI  - Canine bladderworm (Capillaria plica) infection associated with glomerular
      amyloidosis.
AB  - Capillaria plica (Trichuroidea: Capillariidae), commonly known as bladderworm, is
      a nematode rarely associated with clinical disease that resides in the lower
      urinary tract of wild and domestic canids. In the present paper a case of canine
      urinary capillariosis associated with glomerular amyloidosis is described. The
      dog, an 8-year-old, male, hunting Jagd terrier had a history of weight loss and
      diarrhoea and was referred to the University of Parma Teaching Veterinary
      Hospital (UPTVH). Clinical and laboratory tests shown here suggest that C. plica
      may be a contributing factor to glomerular amyloidosis.

PMID- 20034746
TI  - Staged serial debridement and one stage grafting under local anaesthesia. A bed
      side procedure.

PMID- 20034747
TI  - Chronic exposure to cereal mycotoxin likely citreoviridin may be a trigger for
      Keshan disease mainly through oxidative stress mechanism.
AB  - The origin of Keshan disease (KD), an endemic cardiomyopathy particularly
      affected children and young women in China, has been a controversial and
      difficult problem in academics over the past decades. We hypothesize that
      mycotoxins likely citreoviridin may initiate KD mainly through oxidative stress
      mechanism by long-term consumption of mouldy cereals due to food shortage
      lifestyle. Dietary deficiency of selenium, proteins, Vitamin C, E, etc., may act
      as enhancing factors to exacerbate the pathological damage. This speculation can
      perfectly explain the features of KD and has received strong supporting
      evidences. If the hypothesis were to be confirmed, it is of very important value
      in monitoring and blocking the incidence of KD. Thus, future efforts are needed
      to investigate specific biomarkers of exposure to citreoviridin in KD cases.

PMID- 20034749
TI  - An ultra-miniinvasive treatment for stress urinary incontinence in complicated
      older patients.
AB  - OBJECTIVE: To evaluate use of bulking agents (polydimethylsiloxane) as an
      alternative treatment of female stress urinary incontinence (SUI) in older
      patients. STUDY DESIGN: Prospective cohort study. MAIN OUTCOME MEASURES: Women
      with age >75 years old, affected by stress urinary incontinence, presenting to
      our institution between January 2005 and January 2008 were considered for
      eligibility in this prospective study. All patients were submitted to
      transurethral implantation using Macroplastique Implantation System (MIS)
      (Uroplasty, Minneapolis, Minnesota). Cure of SUI was defined as the resolution of
      SUI symptoms. Objective cure rate was assessed by urogynecological physical
      examination and urodynamic assessment performed at 6 and 12 months after surgery
      respectively. Subjective cure rate was assessed during the interview of the 12th
      month with a visual analogue scale (VAS) for quantification of SUI severity and a
      standardized question about the repeatability of the procedure. RESULTS: A total
      of 27 consecutive patients were enrolled in this study. After 12 months of
      surgery the objective cure rate was 44% (12 of 27 patients), the improvement rate
      was 33% (9 of 27) and the failure rate was 22% (6 of 27). The overall success
      rate was 77% (12 patients cured and 9 improved). 23 (85%) patients would like to
      repeat this surgical procedure if necessary. CONCLUSION: Transurethral
      implantation of bulking agents should be considered as alternative treatment of
      SUI in complicated older patients.

PMID- 20034748
TI  - Protective efficacy and immunogenicity of an inactivated avian-origin H3N2 canine
      influenza vaccine in dogs challenged with the virulent virus.
AB  - Transmission of avian-origin influenza A virus (H3N2) to dogs had been reported
      and since then the H3N2 virus infection across South Korea has been occurred
      repeatedly in the country's animal clinics and kennels. Dog-to-dog transmission
      of the virus had also been experimentally demonstrated by direct contact. In this
      study, immunogenicity and protective efficacy against challenge exposure of the
      formalin-inactivated H3N2 influenza virus vaccine with a synthetic polymer
      adjuvant was investigated in dogs. The beagle puppies received two inactivated
      vaccine injections intramuscularly 2 weeks apart. Serological investigation by a
      hemagglutination inhibition (HI) test and an ELISA assay indicated that a
      significant increase in antibody titer was displayed 2 weeks after the second
      vaccination. Clinical signs, virus shedding and histopathological lesions in the
      lungs were exhibited in unvaccinated beagle puppies directly challenged through
      an intranasal route with the virus 2 weeks after the second vaccination. However,
      the vaccinated animals did not show any clinical signs and showed milder
      pathological lung lesions and shorter shedding duration with lower loads than
      controls'. These results indicated that the synthetic polymer-adjuvant avian
      origin canine influenza virus (CIV) vaccine had produced antibody response and
      protection from avian-origin CIV challenge in dogs.

PMID- 20034750
TI  - Application of simple Bayesian statistics to a sample database for source
      correspondence.
AB  - Bayesian statistics was applied to a small sample database of the tensile
      properties of five different brands of writing paper which were perceptibly
      similar. The measured parameters in the database were found to overlap for the
      five brands. This posed a limitation to the application of the classical approach
      for "match" or "no match". It was found that using Bayesian statistics for source
      correspondence, a mere 2-3 measurements corresponding to a particular brand
      raised the probabilities associated with that brand to as high a 72% and
      eliminating a couple of brands.

PMID- 20034751
TI  - Clinical features of 5 patients with descending necrotizing mediastinitis
      originating from deep neck infection.
AB  - Descending necrotizing mediastinitis originating from deep neck infection is one
      of the most serious diseases in the head and neck region. Delayed diagnosis leads
      to death. We examined 5 cases of descending necrotizing mediastinitis,
      successfully treated with antibiotics and surgical drainage. Abscess was found in
      the lower part of the anterior mediastinum in 3 cases and the posterior
      mediastinum in 2 cases. We first conducted transcervical mediastinal drainage for
      3 cases, however, thoracotomy was eventually required in all cases. For cases of
      abscess in the lower part of the anterior mediastinum, early and aggressive
      surgical drainage in collaboration with thoracic surgeons is very important and
      can improve survival.

PMID- 20034752
TI  - Difference of delayed post-tonsillectomy bleeding between children and adults.
AB  - OBJECTIVE: To analyze the characteristics of post-tonsillectomy bleeding and its
      management comparing with adults. METHODS: A retrospective chart review of 1489
      patients who underwent tonsillectomy in our institution (June 2003-June 2006).
      RESULTS: Post-tonsillectomy bleeding rate was 3.1%, 2.5% and 10.8% in younger
      children (age< or =11 years), older children (12< or =age< or =15 years) and
      adults (age>15 years), respectively. Although adults showed an unimodal peak time
      for onset of post-tonsillectomy bleeding, children showed a bimodal peak time. In
      the younger child group, all of the 28 bleeders had spontaneous hemostasis.
      However, in the older child group, there was no spontaneous hemostasis. Bleeding
      was controlled under local anesthesia in 3 patients and 2 patients required
      general anesthesia for bleeding control. In the adult group, spontaneous
      cessation of bleeding occurred in 25 patients (60.9%) and hemostasis under local
      or general anesthesia was performed in 16 (39.1%) patients. CONCLUSIONS: Post
      tonsillectomy bleeding occurred more frequently in adults than in children.
      Spontaneous hemostasis was more prevalent in children than in adults. Post
      tonsillectomy bleeding in the younger child group was controlled with close
      observation alone.

PMID- 20034753
TI  - Expression of cyclooxygenase-2 and microsomal prostagalandin E synthase-1 in head
      and neck squamous cell carcinoma.
AB  - OBJECTIVE: Our aim was to examine the expression of COX-2 and microsomal
      prostaglandin E synthase-1 (mPGES-1), and compare the results with clinical data.
      PATIENTS AND METHODS: Expression of COX-1, COX-2, and mPGS-1 was evaluated by
      immunohistochemistry in head and neck squamous cell carcinoma (HNSCC) from 25
      patients and mRNA levels were determined by the quantitative reverse
      transcription polymerase chain reaction. RESULTS: COX-2 overexpression was noted
      in tumor cells from 19 of the 25 carcinoma patients and mPGES was expressed by
      tumor cells from 21 patients. Localization of COX-2 and mPGES-1 was very similar,
      and well-differentiated tumors showed stronger expression than poorly/moderately
      differentiated tumors. The COX-2/GAPDH and mPGES/GAPDH mRNA ratios were
      significantly higher in well-differentiated carcinomas and N0 patients.
      CONCLUSIONS: There was overexpression of COX-2 and its downstream enzyme mPGES-1,
      and their localization in tumor cells was similar, suggesting that these enzymes
      play both an important role in the development and proliferation of HNSCC.
      Furthermore, COX-2 and mPGES-1 were strongly expressed by well-differentiated
      carcinomas, suggesting their involvement in the differentiation of cancer.

PMID- 20034754
TI  - Differential expression of hippocampal connexins after acute hypoxia in the
      developing brain.
AB  - Acute hypoxia at postnatal day (P) 10 is an accepted model of human neonatal
      hypoxia which results, among other consequences, in increased hippocampal
      excitability. Hypoxic-ischemic injury, which mimics stroke, has been shown to
      result in changes in connexins (Cxs), however, changes in Cxs have not been
      studied in the P10 hypoxia model. The aim of this study was to investigate
      changes in the hippocampal expression of three different connexins at consecutive
      developmental stages after acute hypoxia at P10 (10min and 30min after
      reoxygenation, P11, P14, P17, P29, and P45) as compared to sham manipulated pups.
      After acute hypoxia at P10, Cx30 protein levels were increased at 30min after
      reoxygenation, at P11 and at P14, and then returned to control levels. Cx36
      protein levels transiently decreased at P11 after acute hypoxia then returned to
      control levels. Cx43 protein levels did not change at any of the time points.
      Although changes in mRNA expression were observed during development for Cx30
      only, acute hypoxia did not result in changes in mRNA expression of all these Cxs
      when compared to age matched controls suggesting that acute hypoxia induced
      posttranslational changes in protein expression.

PMID- 20034755
TI  - Biopharmaceutical and pharmacokinetic characterization of matrine as determined
      by a sensitive and robust UPLC-MS/MS method.
AB  - The purpose of this research was to develop a sensitive and reproducible UPLC
      MS/MS method to analyze matrine, an anticancer compound, and to use it to
      investigate its biopharmaceutical and pharmacokinetic behaviors in rats. A
      sensitive and fast UPLC-MS/MS method was successfully applied to determine
      matrine in rat plasma, intestinal perfusate, bile, microsomes, and cell
      incubation media. The absolute oral bioavailability of matrine is 17.1+/-5.4% at
      a dose of 2mg/kg matrine. Matrine at 10microM was shown to have good permeability
      (42.5x10(-6)cm/s) across the Caco-2 cell monolayer, and the ratio of P(A-B) to
      P(B-A) was approximately equal to 1 at two different concentrations (1 and
      10microM). Perfusion study showed that matrine displayed significant differences
      (P<0.05) in permeability at different intestinal regions. The rank order of
      permeability was ileum (highest, P(w)=6.18), followed by colon (P(w)=2.07),
      duodenum (P(w)=0.61) and jejunum (P(w)=0.52). Rat liver microsome studies showed
      that CYP and UGTs were not involved in matrine metabolism. In conclusion, a
      sensitive and reliable method capable of measuring matrine in a variety of
      matrixes was developed and successfully used to determine absolute oral
      bioavailability of matrine in rats, transport across Caco-2 cell monolayers,
      absorption in rat intestine, and metabolism in rat liver microsomes.

PMID- 20034756
TI  - The role of counseling for obstetric fistula patients: lessons learned from
      Eritrea.
AB  - OBJECTIVE: The goal of this study was to evaluate the first formal counseling
      program for obstetric fistula patients in Eritrea. METHODS: To evaluate the
      impact of the counseling program, clients were interviewed both before pre
      operative counseling and again after post-operative counseling. A questionnaire
      was used in the interviews to assess women's knowledge about fistula, self
      esteem, and their behavioral intentions for health maintenance and social
      reintegration following surgical repair. In addition, two focus groups were
      conducted with a total of 19 clients assessing their experiences with the
      surgical care and counseling. RESULTS: Data from the questionnaires revealed
      significant improvements in women's knowledge about fistula, self-esteem, and
      behavioral intentions following counseling. Focus group data also supported
      increased knowledge and self-esteem. CONCLUSION: Evaluation of the short-term
      impact of an initial formal counseling program for fistula patients in sub
      Saharan Africa affirmed the positive effects that such a program has for fistula
      patients, with increased knowledge about the causes of fistula, fistula
      prevention and enhanced self-esteem. PRACTICAL IMPLICATIONS: Culturally
      appropriate counseling can be incorporated into services for surgical repair of
      obstetric fistula in low-resource settings and has the potential to improve the
      physical and mental well-being of women undergoing fistula repair.

PMID- 20034757
TI  - Evidence for a synchronous operative approach in the treatment of colorectal
      cancer with hepatic metastases: a case matched study.
AB  - BACKGROUND: Traditionally, a staged operative approach has been used for patients
      with synchronous colorectal cancer and liver metastases in the U.K. With improved
      outcomes from hepatic resection the role of a synchronous operative approach
      needs re-evaluated. METHODS: 32 consecutive patients with colorectal cancer and
      hepatic metastases that underwent a synchronous operative approach were
      individually case matched (according to: age; sex; ASA grade; type of hepatic and
      colonic resection) with patients that had undergone a staged approach. The
      following variables were analysed: operative blood loss; in hospital morbidity
      and mortality; duration of hospital stay; disease free and overall survival.
      RESULTS: Operative blood losses were: synchronous group, median 475mL (range 150
      850mL) vs median 425mL (range 50-1700mL), (p>0.050). There were no significant
      differences in morbidity: (34% synchronous group vs 59%, p=0.690) with no
      recorded mortality. Synchronous group had a shorter hospital stay (median 12 days
      [range 8-21] vs 20 [range 7-51], p=0.008). There were no statistical differences
      between synchronous and staged patients for disease free and overall survival: 10
      months (95% CI 5.8-13.7) versus 14 (95% CI 12.2-16.3; p=0.487) and 21% versus 24%
      at 5 years (p=0.838). CONCLUSION: This present study provides supporting evidence
      for synchronous operative procedures in patients with colorectal liver
      metastases.

PMID- 20034758
TI  - Host prostaglandin EP3 receptor signaling relevant to tumor-associated
      lymphangiogenesis.
AB  - Prostaglandin E(2) (PGE(2)) and prostaglandin E (EP) receptor signaling pathways
      have been implicated in the promotion of tumor growth and angiogenesis. However,
      little is known about their roles in lymphangiogenesis during tumor development.
      The present study evaluates whether endogenous PGE(2) exhibits a critical role in
      tumor-associated lymphangiogenesis. Treatment of male C57BL/6 mice with a
      cyclooxygenase-2 inhibitor, celecoxib, for seven days resulted in a 52.4%
      reduction in tumor size induced by subcutaneous injection of murine Lewis lung
      cells. Celecoxib treatment down-regulated the expression of vascular endothelial
      growth factor receptor (VEGFR)-3 in stromal tissues by 73.9%, and attenuated
      expression of podoplanin, a marker for lymphatic endothelial cells. To examine
      the role of host PGE receptor signaling, we tested four kinds of EP receptor
      knockout mice. At Day 7 after tumor cell implantation, EP3 receptor knockout
      mice, but not EP receptor knockout mice lacking EP1, EP2, or EP4, exhibited a
      53.3% reduction in tumor weight, which was associated with a 74.5% reduction in
      VEGFR-3 mRNA expression in tumor stromal tissues. At Day 14, VEGFR-3 expression
      in EP3-/- mice remained significantly lower than that of their wild-type (WT)
      counterparts. The expression of VEGF-C in the tumor stromal tissues in EP3-/-
      mice were also reduced by 22.1% (Day 7) and 44.1% (Day 14), respectively. In
      addition, the level of immunoreactive podoplanin in the tumor tissues from EP3-/-
      mice was less than that of WT. These results suggest that host EP3 receptor
      signaling regulates tumor-associated lymphangiogenesis by up-regulating
      expression of VEGF-C and its receptor, VEGFR-3, in tumor stromal tissues. Host
      EP3 blockade together with COX-2 inhibition may be a novel therapeutic strategy
      to suppress tumor-associated lymphangiogenesis.

PMID- 20034759
TI  - [Atherosclerotic carotid stenosis in women].
AB  - Atherosclerotic carotid stenosis is a risk factor for myocardial infarction, for
      vascular death, and for stroke. Medical treatment for atherosclerotic carotid
      stenosis routinely includes screening for and treatment of both risk factors and
      other atherosclerotic sites, the prescription of antiplatelets drugs, and patient
      education about transient ischemic accidents. The benefits of carotid surgery
      have been demonstrated in symptomatic stenoses with stenosis of 70% or more. In
      women, the benefits of surgery are slight for asymptomatic stenosis exceeding >
      60% and for moderate symptomatic stenosis (50-69%). The treatment decision
      requires consideration of individual factors such as age, characteristics of the
      stenosis, and the type of symptoms (hemispheric or retinal). Carotid angioplasty
      is not yet sufficiently safe to replace endarterectomy in patients with
      atherosclerotic carotid stenosis. It can be proposed only after multidisciplinary
      consultation for patients at high risk of recurrence under medical treatment and
      in cases of major comorbidity contraindicating carotid surgery or of upper
      cervical stenosis not accessible to surgery.

PMID- 20034760
TI  - Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis.
AB  - Psoriasis and Psoriatic Arthritis (PsA) are chronic inflammatory diseases that
      have a major impact on health. The prevalence and incidence estimates of these
      two closely related diseases show ethnic and geographic variations, being
      generally more common in the colder north than in the tropics. In Europe the
      prevalence of psoriasis varies anywhere from 0.6 to 6.5%. In the USA, the
      estimated prevalence of diagnosed psoriasis is 3.15%. The prevalence in Africa
      varies depending on geographic location, being lowest in West Africa. Psoriasis
      is less prevalent in China and Japan than in Europe, and is entirely absent in
      natives of the Andean region of South America. There are fewer reports on the
      incidence of psoriasis, but a recent study from Rochester, USA showed an
      increasing trend over the last 2 decades. The prevalence of PsA also shows
      similar variation, being highest in people of European descent and lowest in the
      Japanese. Although, study methodology and case definition may explain some of the
      variations, genetic and environmental factors are important. Genetic
      epidemiologic studies have shown that both diseases have a strong genetic
      component. The strongest association is with HLA-Cw*06. Associations with a
      number of genes including IL12B and IL23R have recently been confirmed.
      Environmental risk factors including streptococcal pharyngitis, stressful life
      events, low humidity, drugs, HIV infection, trauma, smoking and obesity have been
      associated with psoriasis and PsA. Here we have reviewed the current literature
      on the epidemiology and genetics of psoriasis and PsA.

PMID- 20034761
TI  - Defining and analyzing geoepidemiology and human autoimmunity.
AB  - Autoimmune diseases cumulatively affect 5-10% of the industrial world population
      and are a significant cause of morbidity and mortality. In recent decades rates
      are rising worldwide, and autoimmunity can no longer be associated solely with
      the more developed "Western" countries. Geoepidemiology of autoimmune diseases
      portrays the burden of these illnesses across various regions and ethnic
      populations. Furthermore, Geoepidemiology may yield important clues to the
      genetic and triggering environmental mechanisms of autoimmunity. In this review
      we compiled and discuss in depth abundant geoepidemiological data pertaining to
      four major autoimmune conditions, namely type-1 diabetes mellitus, multiple
      sclerosis, autoimmune thyroid disease, and inflammatory bowel disease. The
      following key results manifested in this review: 1) Ethno-geographic gradients in
      autoimmune disease risk are attributable to a complex interplay of genetic and
      environmental pressures. 2) Industrial regions, particularly Northern Europe and
      North America, still exhibit the highest rates for most autoimmune diseases. 3)
      Methods particularly useful in demonstrating the significant influence of genetic
      and environmental factors include comparative ethnic differences studies,
      migration studies, and recognition of 'hotspots'. 4) Key environmental
      determinants of geographical differences include diminished ultraviolet radiation
      exposure, Western or affluence-related lifestyle, infection exposure,
      environmental pollutants, nutritional factors and disease-specific precipitants
      (e.g., iodine exposure).

PMID- 20034762
TI  - Effects of early postnatal caffeine exposure on seizure susceptibility of rats
      are age- and model-dependent.
AB  - Repeated caffeine treatment during early postnatal period led to a decreased
      sensitivity to convulsant action of drugs interfering with inhibitory systems. To
      know if it is a general effect we studied convulsant action of agonists of
      glutamate receptors N-methyl-d-aspartate (NMDA) and kainic acid (KA). Early (the
      first day after the last injection) and delayed (at postnatal day (P) 25)
      consequences of daily administration of caffeine at P7-P11 or P13-P17 days were
      studied. Two doses (one submaximal and one supramaximal) of either drug were
      chosen for each age group on the basis of our older data demonstrating decreasing
      sensitivity during postnatal development. Both early and delayed proconvulsant
      effects of submaximal doses of either agonist were observed in P7-P11 groups,
      early effect was markedly expressed; the effects of the supramaximal doses were
      not affected. The other administration group (P13-P17) also exhibited an
      increased sensitivity to convulsant action but delayed effects were more
      pronounced than early consequences especially with supramaximal doses of both
      agonists. In contrast to a decreased sensitivity to drugs suppressing inhibitory
      systems, seizures induced by glutamate receptor agonists are potentiated in
      caffeine-treated immature rats. Timing of caffeine administration and interval
      between the last exposure and testing play an important role.

PMID- 20034763
TI  - Long-term face memory as a measure of right temporal lobe function in TLE: the
      Alsterdorfer Faces Test.
AB  - There is a shortage of neuropsychological tests to assess right temporal lobe
      memory function in TLE patients. Although right temporal lobe dominance for face
      memory is well established, neuropsychological studies on face memory in epilepsy
      surgery candidates have reported mixed results. These latter studies in TLE
      patients mostly concentrated on immediate face recognition. There is evidence
      suggesting that increasing test delays raise the sensitivity of
      neuropsychological face recognition tests to predict face memory decline after
      right temporal lobectomy. Long-term face recognition may also help in
      lateralizing right TLE in preoperative patients with little or no hippocampal
      sclerosis. In this context, we will introduce the Alsterdorfer Faces Test, a
      computerized long-term face memory test developed in the clinical context of an
      epilepsy center.

PMID- 20034764
TI  - CD109 expression levels in malignant melanoma.

PMID- 20034765
TI  - Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug
      resistant (XDR) Enterobacteriaceae isolates to fosfomycin.
AB  - The advancing antimicrobial drug resistance among Enterobacteriaceae renders the
      evaluation of potential novel therapeutic options necessary. We sought to
      evaluate the in vitro antimicrobial activity of fosfomycin against multidrug
      resistant (MDR) Enterobacteriaceae isolates. Antimicrobial susceptibility to
      fosfomycin and 12 additional antibiotics of MDR Enterobacteriaceae isolates
      collected between November 2007 and April 2009 at the University Hospital of
      Heraklion, Crete, Greece, was examined using the Etest method. A total of 152 MDR
      Enterobacteriaceae isolates were studied, including Klebsiella pneumoniae
      (76.3%), Escherichia coli (17.1%), Proteus mirabilis (4.6%) and other species
      (2.0%). Antimicrobial susceptibility rates were highest for fosfomycin (92.8%),
      tigecycline (92.1%) and colistin (73.0%) followed by imipenem (35.5%),
      tetracycline (20.4%), gentamicin (19.7%), trimethoprim/sulfamethoxazole (12.5%)
      and ciprofloxacin (10.5%). Of the 152 isolates, 85 (55.9%) were extensively drug
      resistant (XDR), of which 78 (91.8%) remained susceptible to fosfomycin.
      Susceptibility to fosfomycin of the 79 carbapenemase-producing, 34 extended
      spectrum beta-lactamase-producing and 24 metallo-beta-lactamase-producing
      isolates was 94.9%, 94.1% and 83.3%, respectively. In conclusion, in this study
      fosfomycin exhibited good in vitro antimicrobial activity against MDR and XDR
      Enterobacteriaceae. We suggest further evaluation of the potential clinical
      utility of fosfomycin against infections caused by these pathogens.

PMID- 20034766
TI  - Synergistic effects of dexamethasone and quinolones on human-derived tendon
      cells.
AB  - Quinolones and glucocorticoids are frequently used drugs that may cause
      tendinopathy as a rare adverse effect. We exposed human tenocyte cultures to the
      steroid dexamethasone alone or in combination with either ciprofloxacin or
      levofloxacin at concentrations of 3mg/L and 10mg/L. At concentrations
      corresponding to peak levels in plasma and tissues during therapy (ca. 3-10mg/L),
      ciprofloxacin caused a significant decrease in collagen type I and the beta(1)
      integrin receptor. In contrast, no corresponding effect was induced by 3mg/L
      levofloxacin. With both quinolones at 3mg/L and 10mg/L, the amount of matrix
      metalloproteinase-1 (MMP-1) and MMP-13 was increased. In addition, 3mg/L
      ciprofloxacin and 10mg/L levofloxacin activated caspase-3. Apoptotic changes were
      confirmed by electron microscopy. Incubation of human tenocytes with
      dexamethasone decreased the main matrix protein collagen type I, the
      transmembrane beta(1)-integrin receptor and the cytoskeleton protein vinculin,
      but only at the high concentrations tested (0.1 microM or 10 microM).
      Concentrations of 0.1 microM and 10 microM dexamethasone increased the amount of
      MMPs and activated caspase-3 as an indicator of apoptosis. Combined exposure to
      quinolones and dexamethasone led to more pronounced effects in tenocyte cultures
      at most of the analysed endpoints. The clinical observations of an increased risk
      of quinolone-induced tendinopathy by glucocorticoids are supported by these in
      vitro data.

PMID- 20034767
TI  - In vivo selection of imipenem-resistant Klebsiella pneumoniae producing extended
      spectrum beta-lactamase CTX-M-15 and plasmid-encoded DHA-1 cephalosporinase.
AB  - Four Klebsiella pneumoniae isolates (KP1-4) were recovered sequentially from an
      infected patient. Whilst KP1-3 were resistant to all beta-lactams except
      carbapenems, KP4 recovered after 24 days of imipenem-containing treatment showed
      additional resistance to carbapenems. No carbapenem hydrolysis could be
      identified in KP4. Molecular characterisation revealed that KP1-4 were
      indistinguishable by pulsed-field gel electrophoresis, contained a 95-kb self
      transferable plasmid harbouring bla(CTXM-15) and bla(TEM-1) genes and a 65-kb
      plasmid that was not transferred by conjugation into Escherichia coli, and
      harboured the plasmid-mediated bla(DHA-1) AmpC beta-lactamase gene. In addition,
      KP4 failed to express OmpK36 owing to a point mutation leading to a premature
      stop of the protein. This study demonstrates development of carbapenem resistance
      related to loss of OmpK36 expression in a K. pneumoniae isolate harbouring
      extended-spectrum beta-lactamase and plasmid-mediated cephalosporinase genes
      following prolonged imipenem exposure.

PMID- 20034768
TI  - Theory of mind in obsessive-compulsive disorder: Comparison with healthy
      controls.
AB  - AIM: Theory of mind (ToM) is the ability to represent one's own or another's
      mental states and has been found to be impaired in many psychiatric disorders.
      Our objective was to compare ToM abilities of patients with obsessive-compulsive
      disorder (OCD) with healthy controls and to investigate the relation between some
      illness features, other cognitive functions and ToM abilities of patients.
      METHOD: Thirty OCD patients and age, sex and education matched 30 healthy
      controls were compared according to their performances on ToM tasks (including
      first and second order false belief, hinting task and double-bluff task), verbal
      memory processes test, Weschler memory test (WMT) (logical memory, visual
      reproduction and digit span sub-tests), stroop test. RESULTS: Patients'
      performances were worse than healthy controls on all of the ToM tasks, but the
      results were significant for only for double-bluff task (t=-3.992, df=36.157,
      p<0.01). Performance on double-bluff task was significantly and positively
      correlated with visual reproduction-immediate recall (r=-0.411, p<0.05) and
      visual reproduction-delayed recall (r=0.478, p<0.05), hinting task was
      significantly and positively correlated with verbal memory (r=0.481, p<0.05).
      CONCLUSION: These results show "basic" ToM abilities of OCD patients are
      generally preserved, but they show significant reduction in their "advanced" ToM
      abilities, which seem to be related to their reduced memory capacities. The
      possible reasons for the relation between memory and ToM impairments, as well as
      the clinical significance of ToM deficits in OCD are discussed.

PMID- 20034769
TI  - Characterization and release behaviors of porous PCL/Eudragit RS microcapsules
      containing tulobuterol.
AB  - In this work, porous poly(epsilon-caprolactone) (PCL)/Eudragit RS 100 (ERS-100)
      microcapsules containing tulobuterol base as a model drug were prepared by a
      solvent evaporation method and the effect of the quaternary ammonium groups of
      ERS-100 on the release behaviors of the microcapsules was investigated. The
      microcapsules prepared with PCL alone showed a stable and smooth surface, whereas
      porous microcapsules were formed with the addition of ERS-100. Drug loading and
      encapsulation efficiency of the microcapsules were slightly decreased with an
      increase of ERS-100 content, resulting from an increase in the porosity of the
      microcapsules. In an acidic release medium, PCL microcapsules showed slow drug
      release, whereas PCL/ERS-100 microcapsules showed a faster release rate with an
      increasing ERS-100 content. These behaviors are likely due to an increase in the
      diffusion rate of the drugs stemming from an increased hydration of the
      microcapsules, which results from the interaction between the carboxyl group of
      the release medium and the quaternary ammonium group of ERS-100.

PMID- 20034770
TI  - [Vaso-occlusive crisis of sickle cell child in Brazzaville drugs news].

PMID- 20034771
TI  - [Oesophageal atresia: management in Sub Saharian countries].

PMID- 20034772
TI  - Frequency of screening magnetic resonance imaging to detect occult spinal cord
      compromise and to prevent neurological deficit in metastatic castration-resistant
      prostate cancer.
AB  - AIMS: Neurological deficit from malignant spinal cord compression (SCC) is a
      major complication of metastatic castration-resistant prostate cancer (CRPC). The
      aims of the present study were to determine the incidence of neurological deficit
      in metastatic prostate cancer patients and to determine the optimal frequency of
      screening magnetic resonance imaging (MRI) spine required to detect clinically
      occult radiological SCC (rSCC). MATERIALS AND METHODS: A retrospective analysis
      of the clinical data of 130 consecutive patients with CRPC, with no functional
      neurological deficit, who had screening MRI spine from January 2001 to May 2005,
      was undertaken. Patients found to have rSCC received radiotherapy. All patients
      were followed-up to document the incidence of neurological deficit. RESULTS:
      Thirty-seven (28.4%) patients had rSCC on MRI. The proportion of patients free
      from neurological deficit at 3, 6, 12, 18 and 24 months was 94, 80, 59 and 43%,
      respectively, in patients who had rSCC on initial MRI and 97.5, 89, 75 and 63%,
      respectively, in patients who had no rSCC. A high prostate-specific antigen (PSA)
      level at initial MRI (P = 0.035) and a short PSA doubling time < 3 months (P =
      0.009) significantly predicted for neurological deficit on univariate analysis,
      whereas back pain (P = 0.059), although an important predictive factor, did not
      attain statistical significance. On multivariate analysis, only rapid PSA
      doubling time (<3 months) independently predicted for future neurological deficit
      (P = 0.042). CONCLUSION: MRI spine can be used to detect asymptomatic rSCC in
      patients with CRPC and serial estimations are required to maintain a low
      incidence of clinical SCC. If serial screening MRI spine is used to detect rSCC
      in 90% of patients before the development of neurological signs, the optimum
      frequency depends on the subset of patients studied. The results of our study
      suggest that the optimum frequency would be every 4-6 months for patients with
      previous SCC, rapid or high PSA or back pain and annually for asymptomatic
      patients.

PMID- 20034773
TI  - Lack of promoting effects from physical pulmonary collapse in a female A/J mouse
      lung tumor initiated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      with remarkable mesothelial cell reactions in the thoracic cavity by the polymer.
AB  - Experimental identification of potential chemopreventive or tumor promotive
      agents in the lung is important. Establishment of short-term bioassay models is
      therefore a high priority. In an attempt to induce strong promotion effects, in
      Experiment 1, left thoracotomy was performed on A/J mice at week 3 after
      initiation with 4-(methylnitrosamno)-1-(3-pyridyl)-1-butanone (NNK) (2mg/0.1 ml
      saline/mouse i.p.) at weeks 0 and 1. In Experiment 2, at week 3, 0.2 ml of
      polymer gel was infused directly into the left cavity of the thorax with
      thoracotomy to occupy certain thoracic cavity volume and to examine the influence
      of physical pulmonary collapse. The experiments were terminated after 8, 10, 12
      and 16 weeks in Experiment 1, and 12 weeks in Experiment 2 but no clear promotion
      effects in either experiment or pulmonary collapse due to infused polymer were
      apparent. However, a pronounced mesothelial cell reaction to the infused polymer
      was evident on the left lung surfaces and parietal pleura in Experiment 2. In
      conclusion, the present experiments did not demonstrate any clear lung tumor
      promotion effects of thoracotomy or physical left lung collapse. It remains
      possible, however, that alternative approaches might have greater efficacy and
      these need more consideration. In addition, mesothelial cells reaction was
      observed with the infused polymer.

PMID- 20034774
TI  - Investigations into the specific effects of rosemary oil at the receptor level.
AB  - Rosemary oil is used frequently in phytotherapy. The objective of the present
      study was to investigate the extent to which rosemary oil shows other effects on
      the smooth muscles than the familiar spasmolytic effects. The effects of rosemary
      oil on the spontaneous contractile activity were investigated in in vitro
      experiments with circular smooth-muscle strips of the guinea pig stomach.
      Rosemary oil was found to have agonistic effects on the alpha(1) and alpha(2)
      adrenergic receptors. These effects can be registered at concentrations up to 25
      microl/l of rosemary oil. At higher concentrations the spasmolytic effect
      described in other reports could be detected. At concentrations above 100
      microl/l rosemary oil, the effect of 10(-5)M ACH is completely suppressed. The
      results permit the assumption that, besides the spasmolytic effects investigated
      to date, owing to its specific effects on the alpha(2) adrenergic receptors of
      the nerve cells, rosemary oil brings about an additional improvement of local
      blood circulation and alleviates pain.

PMID- 20034775
TI  - Isoprostane nomenclature: inherent problems may cause setbacks for the
      development of the isoprostanoid field.
AB  - Do we have to bother about the isoprostane nomenclature? The widely accepted
      IUPAC isoprostane nomenclature provides an unambiguous and systematic terminology
      to name all theoretical possible isoprostanes. However, the currently accepted
      nomenclature system provides an unnatural framework which is not well suited to
      address certain biologically relevant questions. Artificial categorization of
      isoprostanoids into prostanoid families disrupts prostaglandin-ring core
      structures needed to describe biogenetic precursor-product relationships. In
      addition, the IUPAC system defines isoprostanoid families which comprise
      chemically heterogeneous isoprostanoids which largely differ in their
      physicochemical properties from those of the corresponding prostaglandins. As a
      result of this, alternative nomenclature systems such as the phytoprostane
      nomenclature system overcoming some inherent problems of the IUPAC nomenclature
      are still in use. However, different naming of isoprostanoids especially the
      classification of prostanoid family names has created considerable confusion.
      Therefore, a cautionary note on the current use of different nomenclature systems
      is necessary.

PMID- 20034776
TI  - Mammalian autophagy: core molecular machinery and signaling regulation.
AB  - Autophagy, a cellular catabolic pathway, is evolutionarily conserved from yeast
      to mammals. Central to this process is the formation of autophagosomes, double
      membrane vesicles responsible for delivering long-lived proteins and excess or
      damaged organelle into the lysosome for degradation and reuse of the resulting
      macromolecules. In addition to the hallmark discovery of core molecular machinery
      components involved in autophagosome formation, complex signaling cascades
      controlling autophagy have also begun to emerge, with mTOR as a central but far
      from exclusive player. Malfunction of autophagy has been linked to a wide range
      of human pathologies, including cancer, neurodegeneration, and pathogen
      infection. Here we highlight the recent advances in identifying and understanding
      the core molecular machinery and signaling pathways that are involved in
      mammalian autophagy.

PMID- 20034777
TI  - Effect of contact time on the release of contaminants from granular waste
      materials during column leaching experiments.
AB  - When reusing or disposing of contaminated granular waste materials there is a
      need to evaluate how the contaminants will interact on the pathway soil
      groundwater and the effect this interaction will have on the surrounding
      environment. While column testing can provide a closer approximation to field
      percolation conditions than batch testing, there is still a need to develop
      column testing procedures that consider the requirements of practical testing
      time frames. This study evaluates the effect of different column contact times
      (2.5, 5, and 16h) on the release of inorganic constituents from bottom ash and
      demolition waste, two commonly reused granular materials. Leaching data for
      representative constituents of concern, such as copper, chromium, sulfate and
      chloride, as well as pH and electrical conductivity was compared for all
      different contact times studied. Results for the materials investigated in this
      study showed that variations in contact time have no significant effect on the
      release of the selected constituents and leaching parameters at low liquid to
      solid ratios. However, after a liquid to solid ratio of 1L/kg, the effect is more
      noticeable, and higher contact times show lower pH values as well as a reduction
      in the release of constituents of concern from bottom ash. In the case of
      demolition waste, the variation of contact time did not have a strong effect on
      the leaching behavior.

PMID- 20034778
TI  - Co-composting of green waste and food waste at low C/N ratio.
AB  - In this study, co-composting of food waste and green waste at low initial carbon
      to nitrogen (C/N) ratios was investigated using an in-vessel lab-scale composting
      reactor. The central composite design (CCD) and response surface method (RSM)
      were applied to obtain the optimal operating conditions over a range of
      preselected moisture contents (45-75%) and C/N ratios (13.9-19.6). The results
      indicate that the optimal moisture content for co-composting of food waste and
      green waste is 60%, and the substrate at a C/N ratio of 19.6 can be decomposed
      effectively to reduce 33% of total volatile solids (TVS) in 12days. The TVS
      reduction can be modeled by using a second-order equation with a good fit. In
      addition, the compost passes the standard germination index of white radish seed
      indicating that it can be used as soil amendment.

PMID- 20034779
TI  - Synthesis of zeolite from Italian coal fly ash: differences in crystallization
      temperature using seawater instead of distilled water.
AB  - In this study Italian coal fly ash was converted into several types of zeolite in
      laboratory experiments with temperatures of crystallization ranging from 35 up to
      90 degrees C. Distilled and seawater were used during the hydrothermal synthesis
      process in separate experiments, after a pre-treatment fusion with NaOH. The
      results indicate that zeolites could be formed from different kind of Italian
      coal fly ash at low temperature of crystallization using both distilled and
      seawater. SEM data and the powder patterns of X-ray diffraction analysis show
      that faujasite, zeolite ZK-5 and sodalite were synthesized when using both
      distilled and seawater; zeolite A crystallized only using distilled water. In
      particular the experiments indicate that the synthesis of zeolite X and zeolite
      ZK-5 takes place at lower temperatures when using seawater (35 and 45 degrees C,
      respectively). The formation of sodalite is always competitive with zeolite X
      which shows a metastable behaviour at higher temperatures (70-90 degrees C). The
      chemical composition of the fly ash source could be responsible of the
      differences on the starting time of synthesized zeolite with distilled water, in
      any case our data show that the formation of specific zeolites takes place always
      at lower temperatures when using seawater.

PMID- 20034780
TI  - Electrochemical DNA biosensor fabrication with hollow gold nanospheres modified
      electrode and its enhancement in DNA immobilization and hybridization.
AB  - In this article, hollow gold nanospheres (HGN) were prepared by using Co
      nanoparticles as sacrificial templates and varying the stoichiometric ratio of
      HAuCl(4) over the reductants. The HGN was then modified on the electrode surface
      via a 1,6-hexanedithiol linking agent to fabricate a novel electrochemical DNA
      biosensor. The whole DNA biosensor fabrication process was characterized by
      cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods
      with the use of ferricyanide as an electrochemical redox indicator. The probe DNA
      immobilization and hybridization on the modified electrode was further studied
      with CV and differential pulse voltammetry (DPV) methods by using Co(phen)(3)(3+)
      as an electrochemical hybridization indicator. Results revealed that the HGN
      modified electrode, especially for the HGN with the outer surface surrounded by
      densely spike-like nanocrystallites, could largely enhance the DNA hybridization
      ability. The fabricated DNA biosensor was proved to have a low detection limit (1
      pM) and a wide dynamic range (from 1 pM to 10nM) with a high stability and
      reusability.

PMID- 20034781
TI  - Magnetic beads based rolling circle amplification-electrochemiluminescence assay
      for highly sensitive detection of point mutation.
AB  - The identification of point mutations is particularly essential in the fields of
      medical diagnosis and prognosis of many pathogenic and genetic diseases. In this
      study, an rolling circle amplification (RCA) based electrochemiluminescence (ECL)
      assay for highly sensitive point mutation detection was developed. In the assay,
      an allele-discriminating padlock probe was designed for targeting the sequence in
      the p53 oncogene locus. A circular template generated by enzymatic ligation upon
      the recognition of a point mutation (CGT to CAT) on the oncogene could be
      amplified isothermally by Phi 29 DNA polymerase. The elongated products,
      containing hundreds of copies of the circular DNA template sequence, were
      hybridized with Ru(bpy)(3)(2+) (TBR)-tagged probes and then captured onto
      streptavidin-coated paramagnetic beads. The resulting products were analyzed by
      magnetic bead based ECL platform. As low as 2 amol of mutated strands was
      detected by this assay, which could be attributed to the high amplification
      efficiency of Phi 29 DNA polymerase and current magnetic bead based ECL detection
      platform. In addition, the positive mutation detection was achieved with a wild
      type to mutant ratio of 10000:1, due to the high fidelity of DNA ligase in
      differentiating mismatched bases at the ligation site. It is demonstrated that
      this proposed method provides a highly sensitive and specific approach for point
      mutation detection.

PMID- 20034782
TI  - Rationally designed aptamer-based fluorescence polarization sensor dedicated to
      the small target analysis.
AB  - A direct fluorescence polarization (FP) assay strategy, dedicated to the small
      molecule sensing and based on the unique induced-fit binding mechanism of end
      labelled nucleic acid aptamers, has been recently developed by our group. Small
      target binding has been successfully converted into a significant increase of the
      fluorescence anisotropy signal presumably produced by the reduction of the local
      motional freedom of the dye. In order to generalize the approach, a rational FP
      sensor methodology was established herein, by engineering instability in the
      secondary structure of an aptameric recognition element. The anti-adenosine DNA
      aptamer, labelled by a single fluorescein dye at its 3' extremity, was employed
      as a model functional nucleic acid probe. The terminal stem of the stem-loop
      structure was shortened to induce a destabilized/denatured conformation which
      promoted the local segmental mobility of the dye and then a significant
      depolarization process. Upon target binding, the structural change of the aptamer
      induced the formation of a stable stem-loop structure, leading to the reduction
      of the dye mobility and the increase in the fluorescence anisotropy signal. This
      reasoned approach was applied to the sensing of adenosine and adenosine
      monophosphate and their chiral analysis.

PMID- 20034783
TI  - Highly sensitive and selective glutamate microbiosensor based on cast
      polyurethane/AC-electrophoresis deposited multiwalled carbon nanotubes and then
      glutamate oxidase/electrosynthesized polypyrrole/Pt electrode.
AB  - A highly sensitive and selective glutamate microbiosensor based on polypyrrole
      (PPy), multiwalled carbon nanotubes (MWCNT) and glutamate oxidase (GluOx)
      deposited on the transducer platinum electrode (Pt) is described. The sensor
      consists of a permselective membrane of polypyrrole for the rejection of
      interferences, followed by a layer of multiwalled carbon nanotubes and glutamate
      oxidase deposited by asymmetrical alternating current electrophoretic deposition
      (AC-EPD). The biosensor has a high sensitivity (3.84 nA/(microMmm(2))), low
      response to interferences such as ascorbic acid, uric acid and acetaminophen, a
      fast response time (7s), low detection limit (approximately 0.3 microM), a linear
      range of 140 microM and a satisfactory stability. In order to improve the linear
      range and the stability, a thin layer of polyurethane (PU) was applied to the
      Pt/PPy/MWCNT/GluOx sensor. The resulting sensor with the PU outer membrane showed
      an increase in the linear range up to approximately 500 microM glutamate and has
      a better stability at the expense of a decrease in sensitivity (2.5
      nA/(microMmm(2))) and an increase in the response time (15s).

PMID- 20034784
TI  - Estimation of an optimal chemotherapy utilisation rate for breast cancer: setting
      an evidence-based benchmark for the best-quality cancer care.
AB  - BACKGROUND: The proportion of breast cancer patients that received chemotherapy
      varies widely in high-income countries. An evidence-based estimate of the optimal
      chemotherapy utilisation rate for a breast cancer population may serve as a
      useful benchmark for measuring and improving the quality of care. METHODS: An
      optimal chemotherapy utilisation model was constructed using indications for
      chemotherapy identified from evidence-based guidelines. Data on the proportion of
      patient (age, performance status and preference) and tumour (stage, size, grade,
      nodal status, hormone receptor and HER2 status) attributes were obtained and
      merged with the treatment indications to calculate an optimal utilisation rate.
      This model was peer-reviewed by a panel of independent experts. RESULTS:
      Chemotherapy was indicated in 17 of the 24 possible clinical scenarios depicted
      in the optimal utilisation model. The estimated optimal proportion of breast
      cancer patients who should received chemotherapy at least once was 68%.
      Sensitivity analyses showed that the range of optimal rate was 60-69%. The
      optimal rate appears to be substantially higher than the reported actual rates
      (29-49%). CONCLUSION: It is possible to generate an optimal chemotherapy
      utilisation rate in breast cancer to serve as an evidence-based benchmark. The
      optimal chemotherapy utilisation rate in breast cancer has remained largely
      unchanged over the past 15years. The reported actual utilisation rates of
      chemotherapy in breast cancer populations appear to have remained below the
      estimated optimal rate, suggesting that potential opportunities for improvement
      in the compliance to guideline recommended care exist.

PMID- 20034785
TI  - Testing various food-industry wastes for electricity production in microbial fuel
      cell.
AB  - Three food-industry wastes: fermented apple juice (FAJ), wine lees and yogurt
      waste (YW) were evaluated in combination with two sources of inoculum, anaerobic
      sludge and garden compost, to produce electricity in microbial fuel cells.
      Preliminary potentiostatic studies suggested that YW was the best candidate, able
      to provide up to 250 mA/m(2) at poised potential +0.3V/SCE. Experiments conducted
      with two-chamber MFCs confirmed that wine lees were definitely not suitable. FAJ
      was not able to start an MFC by means of its endogenous microflora, while YW was.
      Both FAJ and YW were suitable fuels when anaerobic sludge or compost leachate was
      used as inoculum source. Sludge-MFCs had better performance using YW (54 mW/m(2)
      at 232 mA/m(2)). In contrast, compost-leachate MFCs showed higher power density
      with FAJ (78 mW/m(2) at 209 mA/m(2)) than with YW (37 mW/m(2) at 144 mA/m(2)) but
      YW gave more stable production. Under optimized operating conditions, compost
      leachate MFCs fueled with YW gave up to 92 mW/m(2) at 404 mA/m(2) and 44 mW/m(2)
      in stable conditions.

PMID- 20034786
TI  - Biodesulfurization of gas oil using inorganic supports biomodified with
      metabolically active cells immobilized by adsorption.
AB  - The immobilization of Pseudomonas stutzeri using adsorption on different
      inorganic supports was studied in relation to the number of adsorbed cells,
      metabolic activity and biodesulfurization (BDS). The electrophoretic migration
      (EM) measurements and Tetrazolioum (TTC) method were used to evaluate adsorption
      and metabolic activity. Results indicate that maximal immobilization was obtained
      with an initial load of 14 x 10(8) cells mL(-1) for Al and Sep, whereas Ti
      requires 20 x 10(8) cells mL(-1). The highest interaction was observed in the P.
      stutzeri/Si and P. stutzeri/Sep biocatalysts. The IEP values and metabolic
      activities indicate that P. stutzeri change the surface of supports and maintains
      metabolic activity. A direct relation between BDS activity and the adsorption
      capacity of the bacterial cells was observed at the adsorption/desorption
      equilibrium level. The biomodification of inorganic supports by the adsorption
      process increases the bioavailability of sulphur substrates for bacterial cells,
      improving BDS activity.

PMID- 20034787
TI  - Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1
      protease inhibitors incorporating high affinity P2-ligands.
AB  - A series of stereochemically defined cyclic ethers as P2-ligands were
      incorporated in an allophenylnorstatine-based isostere to provide a new series of
      HIV-1 protease inhibitors. Inhibitors 3b and 3c, containing conformationally
      constrained cyclic ethers, displayed impressive enzymatic and antiviral
      properties and represent promising lead compounds for further optimization.

PMID- 20034788
TI  - Synthetic studies on selective adenosine A2A receptor antagonists: synthesis and
      structure-activity relationships of novel benzofuran derivatives.
AB  - A series of benzofuran derivatives were prepared to study their antagonistic
      activities to the A(2A) receptor. Replacement of the ester group of the lead
      compound 1 with phenyl ring improved the PK profile, while modifications of the
      amide moiety showed enhanced antagonistic activity. From these studies, compounds
      13c, 13f, and 24a showed good potency in vitro and were identified as novel A(2A)
      receptor antagonists suitable for oral activity evaluation in animal models of
      catalepsy.

PMID- 20034789
TI  - Inhibition of acetylcholinesterase by chromophore-linked fluorophosphonates.
AB  - Fluorophosphonate (FP) head groups were tethered to a variety of chromophores (C)
      via a triazole group and tested as FPC inhibitors of recombinant mouse (rMoAChE)
      and electric eel (EEAChE) acetylcholinesterase. The inhibitors showed bimolecular
      inhibition constants (k(i)) ranging from 0.3 x 10(5)M(-1)min(-1) to 10.4 x
      10(5)M(-1)min(-1). When tested against rMoAChE, the dansyl FPC was 12.5-fold more
      potent than the corresponding inhibitor bearing a Texas Red as chromophore,
      whereas the Lissamine and dabsyl chromophores led to better anti-EEAChE
      inhibitors. Most inhibitors were equal or better inhibitors of rMoAChE than
      EEAChE. 3-Azidopropyl fluorophosphonate, which served as one of the FP head
      groups, showed excellent inhibitory potency against both AChE's ( congruent with
      1 x 10(7)M(-1)min(-1)) indicating, in general, that addition of the chromophore
      reduced the overall anti-AChE activity. Covalent attachment of the dabsyl-FPC
      analog to rMoAChE was demonstrated using size exclusion chromatography and
      spectroscopic analysis, and visualized using molecular modeling.

PMID- 20034790
TI  - Synthesis and evaluation of phenylequine for antimalarial activity in vitro and
      in vivo.
AB  - Synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (PQ), is
      reported for the first time. PQ and the two analogues show increased efficacy in
      moving from the chloroquine sensitive D10 to the chloroquine resistant K1 strain
      in vitro. The in vivo efficacy of PQ, and salts thereof, have been determined in
      Plasmodium berghei ANKA and Plasmodium yoelii. Phenylequine hydrochloride has
      shown an ED(50) of 0.81 in P. yoelii (cf chloroquine ED(50)=1.31).

PMID- 20034791
TI  - A study of the effects of substituents on the selectivity of the binding of N
      arylaminomethylene malonate inhibitors to DHODH.
AB  - A series of mono- and di-substituted N-arylaminomethylene malonates have been
      used to probe the potential of utilizing additional H-bonding contacts in the
      ubiquinone binding channel, for selective inhibition between either human or
      Plasmodium DHODH. Altered 'head' group functionalities have been utilized in
      order to probe the role of specific functionalities within the inhibitors in
      terms of enzyme affinity and selectivity.

PMID- 20034792
TI  - Discovery of N-aryl-9-oxo-9H-fluorene-1-carboxamides as a new series of apoptosis
      inducers using a cell- and caspase-based high-throughput screening assay. 2.
      Structure-activity relationships of the 9-oxo-9H-fluorene ring.
AB  - As a continuation of our studies of apoptosis inducing 9-oxo-9H-fluorene-1
      carboxamides as potential anticancer agents, we explored modification of the 9
      oxo-9H-fluorene ring. SAR studies showed that most changes to the 9-oxo-9H
      fluorene ring were not well tolerated, except the 9H-fluorene (2b) and
      dibenzothiophene (2d) analogs, which were about twofold less active than the 9
      oxo-9H-fluorene analog 2a. Significantly, introduction of substitutions at the 7
      position of the 9-oxo-9H-fluorene ring led to compounds 5a-5c with improved
      activity. Compound 5a was found to have EC(50) values of 0.15-0.29 microM against
      T47D, HCT116, and SNU398 cells, about fivefold more potent than the original lead
      2a. As opposed to the original lead compound 2a, compounds 5a-5b were active in a
      tubulin inhibition assay, indicating a change of mechanism of action. The potent
      azido analog 5c could be utilized for target identification.

PMID- 20034793
TI  - Synthesis and hSERT activity of homotryptamine analogs. Part 6: [3+2] dipolar
      cycloaddition of 3-vinylindoles.
AB  - Substituted 1-tosyl-3-vinylindoles undergo [3+2] dipolar cycloaddition with
      cyclic nitrones to afford substituted isoxazoles in good yield and high
      diastereoselectivity. The cycloadducts were readily converted in 4 steps into
      ring constrained homotryptamine analogs. These analogs exhibited excellent
      binding affinity for the human serotonin transporter (hSERT). Indoles bearing a 5
      cyano group and a pendent ethyl(tetrahydroisoquinoline) moiety at the 3-position
      displayed the best potency for hSERT and high selectivity versus hDAT and hNET.

PMID- 20034794
TI  - The contribution of human synovial stem cells to skeletal muscle regeneration.
AB  - Stem cell therapy holds promise for treating muscle diseases. Although satellite
      cells regenerate skeletal muscle, they only have a local effect after intra
      muscular transplantation. Alternative cell types, more easily obtainable and
      systemically-deliverable, were therefore sought. Human synovial stem cells
      (hSSCs) have been reported to regenerate muscle fibres and reconstitute the
      satellite cell pool. We therefore determined if these cells are able to
      regenerate skeletal muscle after intra-muscular injection into cryodamaged
      muscles of Rag2-/gamma chain-/C5-mice. We found that hSSCs possess only limited
      capacity to undergo myogenic differentiation in vitro or to contribute to muscle
      regeneration in vivo. However, this is enhanced by over-expression of human
      MyoD1. Interestingly, hSSCs express extracellular matrix components laminin
      alpha2 and collagen VI within grafted muscles. Therefore, despite their limited
      capacity to regenerate skeletal muscle, hSSCs could play a role in treating
      muscular dystrophies secondary to defects in extracellular matrix proteins.

PMID- 20034795
TI  - Myositis in Griscelli syndrome type 2 treated with hematopoietic cell
      transplantation.
AB  - Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary
      dilution and is occasionally associated with a hemophagocytic syndrome (type 2).
      We present a 13-year-old girl with Griscelli syndrome type 2, who developed a
      hemophagocytic syndrome along with marked muscle weakness and elevated plasma
      creatine kinase. Muscle biopsy showed massive inflammatory changes in some
      fascicles, while other fascicles were relatively spared. Clinical symptoms and
      biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell
      transplantation. Our results suggest that muscle involvement should be considered
      in patients with hemophagocytic syndrome to ensure proper treatment.

PMID- 20034796
TI  - Adjuvant therapy for postmenopausal women with endocrine-sensitive breast cancer.
AB  - Approximately 180,000 women are diagnosed with breast cancer in the United States
      annually. The majority of these women are postmenopausal and have endocrine
      sensitive tumors. Over the last four decades, multiple clinical trials have been
      conducted in efforts to establish and advance adjuvant endocrine therapies. We
      review the available evidence for adjuvant endocrine therapies and current
      recommendations for therapy in postmenopausal women. Although we have made
      substantial progress in the treatment of endocrine-sensitive breast cancer,
      future study will require incorporation of biological and translational questions
      with the goal of enhancing treatment benefits and minimizing toxicity.

PMID- 20034797
TI  - Real-time gait event detection for normal subjects from lower trunk
      accelerations.
AB  - In this paper we report on a novel algorithm for the real-time detection and
      timing of initial (IC) and final contact (FC) gait events. We process the
      vertical and antero-posterior accelerations registered at the lower trunk (L3
      vertebra). The algorithm is based on a set of heuristic rules extracted from a
      set of 1719 steps. An independent experiment was conducted to compare the results
      of our algorithms with those obtained from a Digimax force platform. The results
      show small deviations from times of occurrence of events recorded from the
      platform (13+/-35 ms for IC and 9+/-54 ms for FC). Results for the FC timing are
      especially relevant in this field, as no previous work has addressed its temporal
      location through the processing of lower trunk accelerations. The delay in the
      real-time detection of the IC is 117+/-39 ms and 34+/-72 ms for the FC, improving
      previously reported results for real-time detection of events from lower trunk
      accelerations.

PMID- 20034798
TI  - The use of kinematic and parametric information to highlight lack of movement and
      compensation in the upper extremities during activities of daily living.
AB  - A problem that is common to the study of upper limb kinematics and gait analysis
      is the translation of the evidence from kinematic measurements into easily
      interpretable information on the status of the patient, such as the amount of
      compensation or lack of motion. In this study parameters that can be helpful in
      the rapid and clear identification of limited wrist motion and compensation were
      derived from kinematic data. A group of six subjects (group A) with no hand
      impairment, average age 32.5 ys SD 10.7 ys, and another group of five subjects
      (group B), average age 34.2 ys SD 16.8 ys, having suffered from distal radius
      fracture were tested during a cyclic activity of daily living. The activity
      simulated page turning. Thorax, shoulder, elbow and wrist angles were measured
      during this task using a motion capture system. Corresponding angle ranges were
      also calculated. The active range of motion (AROM) found for Group B was
      generally lower than that of Group A, particularly for elbow supination and wrist
      movements, with wrist flexion/extension statistically smaller for group B
      (P=0.02). Additional parameters that took into account lack of movements at the
      wrist and compensation from shoulder elevation, rotation and elbow
      pronation/supination proved to be more useful at identifying those subjects of
      group B outside the normative range and can provide clinicians with a rapid and
      efficient tool that can shorten the analysis process and help make more informed
      decisions on therapeutic treatments.

PMID- 20034800
TI  - Design and pharmacophore modeling of biaryl methyl eugenol analogs as breast
      cancer invasion inhibitors.
AB  - Cell invasion and migration are required for the parent solid tumor cells to
      metastasize to distant organs. Microtubules form a polarized network, enabling
      organelle and protein movement throughout the cell. Cytoskeletal elements
      coordinately regulate cell's motility, adhesion, migration, exocytosis,
      endocytosis, and division. Thus, microtubule disruption can be a useful target to
      control cancer cell invasion and metastasis. The phenolic ether methyl eugenol
      (1), the major component of the essential oil of the leaves of Melaleuca
      ericifolia Sm. (Myrtaceae), was used as a starting scaffold to design eleven new
      and three known anti-tubulin agents 2-15 using carbon-carbon coupling reactions.
      A computer-assisted approach was used to design these new biaryl derivatives
      using colchicine-binding site of tubulin as the molecular target and colchicine
      as an active ligand. Several derivatives showed potent inhibitory activity
      against MDA-MB-231 cell migration at the 1-4microM dose range. The Z isomers, 4
      and 15 were more active as invasion inhibitors compared to their structurally
      related E isomers, 2 and 14. The cytotoxic activities of compounds 2-15 against
      two breast cancer cell lines MDA-MB-231 and MCF-7 were evaluated. Anti-invasive
      activity of the semisynthetic derivatives is not due to a direct cytotoxic effect
      on MDA-MB-231. Analogs 2-15 may promote their anti-invasive activity through the
      induction of changes in cell morphology. A pharmacophore model was generated
      involving seven essential features for activity, which was consistent with a
      previously generated colchicine site inhibitors model.

PMID- 20034799
TI  - Antitumor agents 270. Novel substituted 6-phenyl-4H-furo[3,2-c]pyran-4-one
      derivatives as potent and highly selective anti-breast cancer agents.
AB  - 6-Phenyl-4H-furo[3,2-c]pyran-4-one derivatives based on neo-tashinlactone (1)
      were synthesized and evaluated as novel anti-breast cancer agents. Compounds 10
      13, 23, 25, and 27 showed potent inhibition against the SK-BR-3 breast cancer
      cell line. Importantly, 25 and 27 showed the highest cancer cell line
      selectivity, being approximately 100-250-fold more potent against SK-BR-3 (ED(50)
      0.28 and 0.44microM, respectively) compared with other cancer cell lines tested.
      In addition, 25 displayed low cytotoxicity against normal breast cell lines 184A1
      and MCF10A. Compounds 25 and 27 merit further investigation in our continuing
      program to generate and develop selective anti-breast cancer agents.

PMID- 20034801
TI  - New thalidomide analogues derived through Sonogashira or Suzuki reactions and
      their TNF expression inhibition profiles.
AB  - A library of new thalidomide C4/5 analogues containing either a phenyl or alkyne
      tether were synthesized using Sonogashira or Suzuki cross coupling reactions from
      their aryl halogenated precursors. All thalidomide analogues were tested for
      their ability to inhibit the expression of the proinflammatory cytokine Tumor
      Necrosis Factor (TNF). More explicitly the use of a novel reporter system
      utilizing the promoter region of the TNF gene in a human T-cell line provided a
      rapid and effective measure of NFkappaB transcriptional activity. Several
      compounds either containing either an aryl-isobutyl or aryl-isopropoxy group were
      the most effective in inhibiting TNF expression, and were several times more
      active than thalidomide itself. Five of the more active derivatives indicated an
      apoptotic response while one of these compounds, containing an aldehyde tether,
      showed possible influence of cell cycling effects.

PMID- 20034802
TI  - Synthesis and biological evaluation of antitumour-active betulin derivatives.
AB  - The reaction of betulinic aldehydes with various carbon nucleophiles gave a
      series of new betulin derivatives, among them epoxides, glycidic derivatives and
      beta-hydroxy carbonyl compounds. Subsequent transformations of the beta-hydroxy
      carbonyls lead to 1,3-diketo- and alpha,beta-unsaturated betulin derivatives.
      These compounds were assayed for cytotoxicity using 15 human cancer cell lines
      and a colorimetric SRB-assay. Several compounds revealed significant antitumour
      activity.

PMID- 20034803
TI  - Influence of water concentrations to chemical forms of tritium generated in
      mercury through a nuclear reaction.
AB  - In order to assess internal doses from tritium at the JSNS (Japan Spallation
      Neutron Source), a correlation between the chemical forms of tritium generated in
      mercury and the amount of water in it was studied by simulating the generation of
      tritium in the mercury target used for a neutron source. The ratio of [(3)H]H(2)O
      to all of generated tritium increased with increase in the water concentration.
      An empirical equation to predict the content of [(3)H]H(2)O from the water
      concentration is proposed.

PMID- 20034805
TI  - Bilateral carcinoma of the temporal bone: case report and literature review.
AB  - INTRODUCTION: Squamous cell carcinoma of the temporal bone is a rare entity. Only
      a few cases have been reported in the literature and even fewer describe
      bilateral tumours. Because its clinical presentation resembles chronic otitis
      media or otitis externa, diagnosis could be delayed. CASE REPORT: A case is
      presented of bilateral squamous cell carcinoma of the temporal bone in a 66 year
      old woman. The patient underwent a left subtotal petrosectomy followed by a right
      subtotal petrosectomy a month later. CONCLUSIONS: Early diagnosis is directly
      related to patient prognosis. However, prognosis remains poor and the surgical
      treatment is a challenge for the experienced skull base surgeon.

PMID- 20034806
TI  - Re-interventions on the autograft and the homograft after the Ross operation in
      children.
AB  - BACKGROUND: For children who require aortic valve replacement, the pulmonary
      autograft may be the ideal substitute. However, re-operations for conduit
      exchange in the pulmonary position are inevitable. In addition, re-operations on
      the autograft may be necessary due to dilatation and neo-aortic insufficiency. We
      sought to assess predictors for re-intervention in an international Ross-operated
      paediatric population. METHODS: Data of 152 children below 16 years of age at the
      time of the Ross operation were analysed using Cox proportional hazard modelling.
      Mean follow-up time was 6.1+/-4.2 years. RESULTS: The median age at the time of
      the Ross operation was 10.1 years (range 54 days to 15 years). Early mortality
      was 2.6%. Survival at 5 and 10 years was 93.9+/-2.0% and 90.4+/-3.1%,
      respectively. Seven patients required autograft re-intervention (explantation n=6
      and reconstruction n=1). Freedom from autograft re-intervention at 5 and 10 years
      was 99.3+/-0.7% and 95.5+/-2.7%, respectively. Prior endocarditis (p=0.061),
      prior aortic regurgitation (p=0.061) and longer follow-up time (p=0.036) emerged
      as risk factors for autograft re-intervention. Seventeen patients required 36
      conduit re-interventions (replacement n=16, percutaneous valvuloplasty n=10).
      Freedom from conduit re-intervention at 5 and 10 years was 89.3+/-2.9% and 79.6+/
      6.1%, respectively. Implantation of an aortic homograft (p=0.013), and smaller
      conduit size (p=0.074) emerged as risk factors for conduit re-intervention.
      CONCLUSIONS: There is a consistent need for conduit re-intervention following the
      Ross operation in children. Re-interventions on the autograft are rare within the
      first decade after surgery. However, the number of autograft re-interventions may
      increase after the first decade, since longer follow-up time is a risk factor for
      autograft failure.

PMID- 20034807
TI  - Bronchogenic pulmonary cyst presenting as haemothorax.

PMID- 20034808
TI  - An early inflammatory response to oesophagectomy predicts the occurrence of
      pulmonary complications.
AB  - BACKGROUND: Respiratory complications are the most frequent concern following
      oesophagectomy. We aimed to assess the postoperative inflammatory response after
      oesophagectomy and to determine its reliability to predict the occurrence of
      pulmonary complications. METHODS: A total of 97 patients were enrolled in this
      prospective observational study. All patients underwent a transthoracic
      oesophagectomy for cancer. From D0 to D3, plasmatic cytokine levels (interleukin
      (IL)-1, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha), short synacthen
      test (SST), PaO(2)/FiO(2) ratio and clinical factors determining the systemic
      inflammatory response syndrome (SIRS) were monitored and compared between
      patients who experienced pulmonary complications (group I) and those who did not
      (group II). RESULTS: The overall in-hospital mortality was 5%. Postoperative
      pulmonary complications occurred in 33 patients (34%). Sputum retention was the
      first step of pulmonary complications in 26 patients (occurring at a mean of
      2.8+/-1 days after the operation), leading to pneumonia in 22 patients (4.7+/-1
      days) and acute respiratory distress syndrome (ARDS) in 10 (6.9+/-3 days). At day
      2, group I patients had significantly higher plasmatic levels of IL-6, IL-10 and
      TNF-alpha than group II patients. PaO(2)/FiO(2) was impaired accordingly (215 vs
      348; p=0.006). SST was negative in 38% of group I patients and in 30% of group II
      patients (p=0.51). SIRS was present in 33% and 6% of group I and group II
      patients, respectively (p< or =0.01). At multivariate analysis, early occurrence
      of SIRS was the sole significant predictor of pulmonary complications (p=0.005;
      odds ratio (OR):11.4, confidence interval (CI): 2-63). CONCLUSIONS: The vast
      majority of postoperative pulmonary complications after oesophagectomy occur
      after the 4th postoperative day. The earlier detection (first 48 h) of SIRS, high
      plasmatic cytokine levels and impairment of PaO(2)/FiO(2) predicts the onset of
      these complications. This finding suggests that early pharmacological
      intervention may have a beneficial impact.

PMID- 20034809
TI  - Angioprevention with fenretinide: targeting angiogenesis in prevention and
      therapeutic strategies.
AB  - Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR;
      fenretinide), a synthetic retinoic acid derivative, is a highly active and
      promising therapeutic and chemopreventive agent. Fenretinide shows biological
      activity against numerous cancer types in vitro and in preclinical studies.
      Clinical trials have shown that fenretinide induces a significant reduction of
      second breast cancer in premenopausal women. Several studies on different
      neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma,
      glioblastoma, head and neck and skin cancers and others. It has minimal side
      effects in humans, so that trials in young women at high-risk of breast cancer
      and ovarian and for the prevention of other tumor types such as lung cancer could
      be envisaged. Here we review some ongoing clinical trials and evaluate the
      possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In
      particular we report basic and translational data on the anti-angiogenic
      "angiopreventive" properties of fenretinide, its anti-invasive activity, its
      ability to induce apoptosis and to generate or enhance production of reactive
      oxygen species as possible molecular bases for a chemopreventive action in
      patients.

PMID- 20034810
TI  - IL-10 promotes resistance to apoptosis and metastatic potential in lung tumor
      cell lines.
AB  - Treatment of non-small cell lung carcinoma (NSCLC) remains at a disappointingly
      low success rate. Not only is metastatic spread common in NSCLC, but therapeutic
      success decreases dramatically once metastases are present. Understanding factors
      which contribute to poor prognosis in NSCLC is critical for development of more
      successful therapeutic approaches. Interleukin-10 (IL-10) expression has been
      shown in several studies to correlate with a poorer prognosis in NSCLC; however,
      the mechanisms by which IL-10 affects lung tumor growth and metastases are
      unclear. The goal of this study was to evaluate the effects of tumor-derived IL
      10 on the growth and metastasis of lung cancer cells in a murine model. Lewis
      lung carcinoma cells were stably transfected with the chicken ovalbumin gene
      (cOVA) as a model tumor antigen (LL43 tumor cells) and subsequently transfected
      with the murine IL-10 gene (LL43-10 tumor cells). Subcutaneous growth of the LL43
      tumor cells was not affected by expression of IL-10. However, LL43-10 tumors had
      a fourfold increase in tumor microvessel density, as indicated by CD31 staining.
      Metastatic potential was also increased in IL-10-expressing lung tumor cells,
      leading to a greater number of tumor cells in lymph nodes draining the primary
      tumor site. Finally, exposure of Lewis lung tumor cells in vitro to exogenous IL
      10 dramatically increased their resistance to UV-induced apoptosis. These results
      indicate that a primary effect of IL-10 on lung cancer cells may be to increase
      their metastatic potential by promoting angiogenesis and resistance to apoptosis.

PMID- 20034811
TI  - High glucose and interleukin-1beta downregulate interleukin-1 type I receptor (IL
      1RI) in retinal endothelial cells by enhancing its degradation by a lysosome
      dependent mechanism.
AB  - Diabetic retinopathy has been considered a low-grade chronic inflammatory
      disease. The production of interleukin-1beta (IL-1beta) in the retina is
      increased, and this finding has been correlated with an increase in blood-retinal
      barrier permeability, suggesting that IL-1beta might have an important role in
      the pathogenesis of diabetic retinopathy. However, in this context, no attention
      has been given to interleukin-1 type I receptor (IL-1RI), which is the receptor
      responsible for IL-1beta triggered effects. Therefore, we investigated the effect
      of high glucose and IL-1beta on the IL-1RI regulation in retinal endothelial
      cells. A time-dependent downregulation of IL-1RI protein levels was detected in
      retinal endothelial cells exposed (1-24h) to high glucose, mannitol or IL-1beta.
      Long-term exposure (7days) to high glucose or mannitol also decreased IL-1RI
      protein content. IL-1RI downregulation was due to its activation by IL-1beta,
      since it was inhibited by the presence of anti-IL-1RI or anti-IL-1beta
      antibodies. Moreover, IL-1RI downregulation was prevented by lysosome inhibitors,
      chloroquine and ammonium chloride, but not by proteasome inhibitors, MG132 and
      lactacystin. We also found that IL-1RI translocates to the nucleus after high
      glucose or IL-1beta treatment. In conclusion, our results indicate that high
      glucose, probably due to osmotic stress, and IL-1beta downregulate IL-1RI in
      retinal endothelial cells. The downregulation of IL-1RI is triggered by its
      activation and is due, at least partially, to lysosomal degradation. High glucose
      and IL-1beta also enhance the translocation of IL-1RI to the nucleus.

PMID- 20034812
TI  - Vipera aspis venom reduces lethality and down-regulates tumor necrosis factor
      alpha in a rat model of LPS-induced sepsis.
AB  - OBJECTIVES: Sepsis and septic shock are major causes of morbidity and mortality
      in critically-ill patients. Sepsis constitutes the systemic response to
      infection, that is predominantly mediated by the pro-inflammatory cytokines TNF
      alpha and IL-1beta. Hence, cytokine modulation provides a promising target for
      the treatment of sepsis. In this work we evaluated the effect of a low-dose
      Vipera aspis venom (VAV) vaccine on survival and cytokine serum levels in a rat
      model of lipopolysaccharide (LPS)-induced septic shock. METHODS: Adult male
      Wistar rats were given either VAV vaccine or saline, and 2 weeks later half of
      each group received LPS challenge, and were monitored for mortality, cytokine
      levels, blood count and chemistry. RESULTS: Survival rate was significantly
      higher in venom-treated, compared to non-vaccinated septic rats. Furthermore, VAV
      treatment significantly reduced LPS-associated TNF-alpha and LDH, without
      affecting IL-6 and IL-10 levels, and modified WBC and platelet counts.
      CONCLUSIONS: Our data suggest that sub-toxic doses of VAV have a protective
      effect against LPS-induced septic shock that may be mediated, at least partially,
      by the modulated TNF-alpha activity. This study thus offers a novel therapeutic
      approach for the attenuation of bacteremia-induced septic shock through the
      modulation of a central pro-inflammatory cytokine by VAV vaccination in mammals.

PMID- 20034813
TI  - Neuromuscular and psychological influences on range of motion recovery in
      anterior cruciate ligament reconstruction patients.
AB  - To identify distinguishing characteristics for knee surgery patients who
      experience a protracted recovery process, we sought to determine if there is an
      association between the neuromuscular stretch reflex and psychological factors of
      pain perception and anxiety on the range of motion (ROM) recovery rate of post
      operative anterior cruciate ligament reconstruction (ACLR) rehabilitation
      patients. The ACLR participants were categorized into a slow recovery group (SRG:
      >6 weeks to recover 0-125 degrees knee flexion [n=10]) and a normal recovery
      group (NRG: <6 weeks to recovery 0-125 degrees knee flexion [n=12]). Control
      participants (n=22) were age, gender and activity-level matched to the surgical
      participants. Neuromuscular testing consisted of sagittal plane video kinematics
      of the Wartenberg Pendulum Test for determining lower limb stiffness indices and
      electromyography-monitored patellar tendon tap reflex responses. Psychological
      and health status assessments consisted of the State-Trait Anxiety Inventory and
      SF-36 Health Survey. Data revealed that neuromuscular reflex profiles, lower limb
      stiffness indices, pain, anxiety and SF-36 indices of function were not
      significantly different between the two surgical groups (SRG and NRG). The
      surgical groups exhibited significantly greater pain (2.67+/-2.27 SRG, 1.49+/
      1.15 NRG) than the control group (p.05). SF-36 indices were significantly lower
      for the surgical groups for total score (546.55+/-94.70 SRG, 577.57+/-125.58
      NRG), function 69.00+/-20.24 SRG, 67.08+/-19.12 NRG), role physical (53.75+/
      22.85 SRG, 53.12+/-23.15 NRG), social (76.24+/-25.31 SRG, 65.62+/-27.24 NRG), and
      emotional (82.49+/-19.81 SRG, 81.38+/-23.02 NRG) subscales (p.05). These results
      suggest that neuromuscular reflex responses, visual analogue scale (VAS) pain,
      and anxiety are not distinguishing factors for ROM recovery rate between the SRG
      and NRG. Decreased SF-36 indices, including pain as it influences function,
      though clinically relevant factors, were not statistically associated with post
      operative ROM recovery rate.

PMID- 20034814
TI  - Management of refractory status epilepticus at a tertiary care centre in a
      developing country.
AB  - BACKGROUND: Refractory status epilepticus (RSE) is a common Neurological
      Emergency with increased mortality and morbidity in developing countries where
      facilities of intubation, adequate ventilation, Intensive Care Units (ICUs) and
      general anaesthesia are not ubiquitously available. Treatment protocols use
      antiepileptic drugs (AEDs) and need ICU facilities after failure of standard
      AEDs. Our aim was to see the response to two additional drugs in the
      armamentarium against refractory status, that is, valproate and levetiracetam.
      METHODS: Patients with generalized RSE admitted in neurology and neurosurgery
      services at AIIMS during December 2006 to June 2008 were included in the study.
      The patients were allotted to two groups based on certain criteria. Demographic
      details, reason for delay, etiology precipitating status, ongoing AEDs therapy,
      duration of status, the time taken for cessation along with clinical, EEG and MRI
      correlates were noted. Outcome parameters were analyzed by an independent blinded
      observer. RESULTS: 82 patients with RSE were studied out of which 41 patients
      were given IV valproate (Group A) and 41 patients were given IV levetiracetam
      (Group B). Cessation of status failed in 13 patients in valproate group and 11
      patients in levetiracetam group. Majority of the patients did not require ICU
      settings despite being classified as refractory. CONCLUSION: RSE can be
      controlled with intravenous loading and maintenance of valproate or levetiracetam
      which do not cause respiratory depression, hypotension, need of intubation and
      ICU care. These must always be considered in a developing country scenario where
      ICU facilities are not always available or while transporting to centres where
      these facilities are available.

PMID- 20034815
TI  - Angio-CT imaging of the spinal cord vascularisation: a pictorial essay.
AB  - Knowledge of the spinal cord (SC) vascular supply is important in patients
      undergoing procedures that involve the thoracic and thoraco-abdominal aorta; the
      SC vasculature, however, has a complex and highly variable anatomy. Recent
      breakthroughs in imaging methods have expanded the non-invasive diagnostic
      ability to determine a patient's spinal cord vascular pattern, particularly in
      detecting the presence and location of the artery of Adamkiewicz. CT is the
      imaging modality of choice for most patients with thoracic and thoraco-abdominal
      aortic disease for pre-operative planning of endovascular treatment: thus the
      data set required for our analysis of spinal cord vascular anatomy is already
      available. This paper provides examples of the SC vasculature imaging that can be
      obtained with 64 row scanners and appropriate postprocessing.

PMID- 20034817
TI  - Response to comments on "Separation of components in fenestrated and branched
      endovascular grafting".

PMID- 20034816
TI  - Residual venous obstruction, alone and in combination with D-dimer, as a risk
      factor for recurrence after anticoagulation withdrawal following a first
      idiopathic deep vein thrombosis in the prolong study.
AB  - OBJECTIVE: This study aims to assess the predictive value of residual venous
      obstruction (RVO) for recurrent venous thrombo-embolism (VTE) in a study using D
      dimer to predict outcome. DESIGN: This is a multicentre randomised open-label
      study. METHODS: Patients with a first episode of idiopathic VTE were enrolled on
      the day of anticoagulation discontinuation when RVO was determined by compression
      ultrasonography in those with proximal deep vein thrombosis (DVT) of the lower
      limbs. D-dimer was measured after 1 month. Patients with normal D-dimer did not
      resume anticoagulation while patients with abnormal D-dimer were randomised to
      resume anticoagulation or not. The primary outcome measure was recurrent VTE over
      an 18-month follow-up. RESULTS: A total of 490 DVT patients were analysed (after
      excluding 19 for different reasons and 118 for isolated pulmonary embolism (PE)).
      Recurrent DVT occurred in 19% (19/99) of patients with abnormal D-dimer who did
      not resume anticoagulation and 10% (31/310) in subjects with normal D-dimer
      (adjusted hazard ratio: 2.1; p = 0.02). Recurrences were similar in subjects
      either with (11%, 17/151) or without RVO (13%, 32/246). Recurrent DVT rates were
      also similar for normal D-dimer, with or without RVO, and for abnormal D-dimer,
      with or without RVO. CONCLUSIONS: Elevated D-dimer at 1 month after
      anticoagulation withdrawal is a risk factor for recurrence, while RVO at the time
      of anticoagulation withdrawal is not.

PMID- 20034818
TI  - Conservative treatment of a pathologic fracture in a patient with Gorham-Stout
      disease.
AB  - Gorham-Stout disease, or massive osteolysis, is an extremely rare idiopathic
      condition characterized by spontaneous, localized relentless resorption of one or
      several contiguous bones. There is no known successful treatment. Autologous bone
      graft also resorbs. It is a condition with difficult diagnosis, treatment, and
      prognosis. We report an extreme case of massive osteolysis of the maxillofacial
      complex. Unique to this case is that the patient presented with a mandibular
      fracture, and was taking alendronate (Fosamax), one of the treatment options for
      patients with Gorham-Stout disease. We discuss our treatment and add to the
      growing list of patients who have presented with this devastating disease.

PMID- 20034819
TI  - Access to the maxillary sinus using a bone flap with sinus mucosal and
      mucoperiosteal pedicles.
AB  - We describe a procedure for removing lesions in the maxillary sinus using bone
      flaps with the sinus mucosa and mucoperiosteum. The surgical design is to
      construct a rectangular trapdoor using 3 consecutive bur-cuts, fracture the upper
      margin, and lift the bone lid upward. The osteotomy site on the inferior, medial,
      and lateral sides of the bone lid was exposed subperiosteally, but the
      mucoperiosteal and sinus mucosal attachments on the superior and central areas of
      the lid were maintained. Then, following fracture of the upper bone margin, the
      lid was lifted upward. In this way, the integrity of the mucoperiosteum and sinus
      mucosa was maintained. Advantages of the bone flap with soft tissue pedicles
      technique may be quick recovery and restored integrity of the sinus wall, with a
      low probability of infection because of vascularization of the bone lid. To
      realize this, a bone flap with both sinus mucosal and mucoperiosteal pedicles is
      more suitable.

PMID- 20034820
TI  - Effectable application of vascular endothelial growth factor to critical sized
      rat calvaria defects.
AB  - OBJECTIVE: An early vascular response for angiogenesis is essential for the
      normal progression of bone defect healing. Vascular endothelial growth factor
      (VEGF) is a potent inducer of angiogenesis. The aim of this study was to evaluate
      the effects of a poly (L,D-lactic-co-glycolic acid) (PLGA) membrane with VEGF
      encapsulated into PLGA microspheres on bone regeneration at bone defects in rat
      calvaria. STUDY DESIGN: Microspheres of PLGA incorporating VEGF(165) (VEGF
      microspheres) were prepared, and critical-size bone defects were created in rat
      calvaria. The VEGF microspheres, PLGA microspheres, or VEGF microspheres plus
      PLGA membrane were applied to the defects. Bone regeneration was evaluated using
      image analysis based on soft radiographic and histologic examination. RESULTS:
      Mature thick bone regeneration was observed in selected sites at bone defects
      that had been applied with VEGF microspheres/PLGA membrane compared with those
      that had been applied with the other treatments. CONCLUSION: A combination of
      VEGF microspheres and a PLGA membrane effectively enhances bone regeneration.

PMID- 20034821
TI  - The levels of vascular endothelial growth factor in the synovial fluid correlated
      with the severity of arthroscopically observed synovitis and clinical outcome
      after temporomandibular joint irrigation in patients with chronic closed lock.
AB  - OBJECTIVE: This study aimed to investigate the level of vascular endothelial
      growth factor (VEGF) in the temporomandibular joint (TMJ) synovial fluid (SF) and
      the severity of arthroscopically observed synovitis before and after visually
      guided TMJ irrigation (VGIR) in patients with chronic closed lock (CCL). In
      addition, the findings were correlated with the clinical outcome. STUDY DESIGN:
      Twenty-four patients with unilateral CCL, who underwent a second VGIR either as a
      repeated therapeutic TMJ irrigation or as a follow-up arthroscopy, were enrolled
      in the study. They were divided into either successful (s-group; n = 11) and
      unsuccessful (u-group; n = 13) groups. The VEGF level in the aspirated SF and the
      severity of synovitis were compared between the s- and u-groups. In each group,
      the same parameters were compared before and after VGIR. The correlation of the
      VEGF level with the severity of synovitis was also studied. RESULTS: At the first
      VGIR, the VEGF levels showed no significant differences when comparing s- and u
      groups. At the second VGIR, the VEGF level was significantly higher in the u
      group. The VEGF level significantly decreased after the first VGIR in the s-group
      but remained unchanged in the u-group. There was no significant correlation
      between the VEGF level and the severity of synovitis. CONCLUSIONS: The level of
      VEGF in TMJ SF seems to reflect the clinical status in patients with CCL.
      Moreover, VEGF may be an important target molecule in future chemotherapy of TMJ
      CCL.

PMID- 20034822
TI  - Dental implants placed into alveolar clefts reconstructed with tongue flaps and
      bone grafts.
AB  - OBJECTIVE: The aim of this study was to describe a case series using surgical and
      prosthodontic modifications of tongue flaps necessary to adapt them for use in
      the reconstruction of large cleft deformities refractory to customary measures
      using dental implants and to study their outcomes in patients with complex cleft
      lip and palate deformities. STUDY DESIGN: Five patients were treated with iliac
      crest bone grafts and covered by anteriorly based tongue flaps divided at either
      3 or 4 weeks after surgery. The patients were followed clinically and
      radiographically for 3-12 years after placement of their dental implants to
      monitor implant survival and success. RESULTS: One of the 5 patients suffered a
      partial tongue flap detachment, graft dehiscence, and recurrence of an oronasal
      fistula, which was successfully treated by shifting the tongue flap tissue from
      its new location in the palate. A total of 18 dental implants were placed into
      bone-grafted tissue covered by the tongue flaps. There was 1 implant failure.
      There were no cases of periimplantitis or bone loss in the 17 surviving implants.
      CONCLUSIONS: Tongue flaps are rarely used clinical entities with a very narrow
      range of indications. Tongue flaps are useful in the preprosthetic reconstruction
      of select cases with large residual oronasal fistulae with soft tissue deficits
      due to scarring from previously failed surgery. Tongue flaps are extremely
      stressful procedures for patients to endure. Patient selection is of the utmost
      importance.

PMID- 20034823
TI  - Management of massive osteolysis of the mandible: a case report.
AB  - The management of a previously reported case of massive osteolysis of the
      mandible with intravenous bisphosphonate, vascularized free bone graft, and
      dental implants is reported. Restoration of adequate cosmetics and masticatory
      function was achieved. Despite the use of bisphosphonates, there were no
      complications with osseointegration. The reconstruction remained stable and
      functional 6 years afterward.

PMID- 20034824
TI  - Nasolabial cyst: case report with CT and MRI findings.
AB  - Nasolabial cysts are uncommon primarily unilateral soft tissue lesions located
      adjacent to the alveolar process above the apices of the maxillary incisors.
      Clinical features of the nasolabial cysts are smooth fluctuant soft tissue
      swelling between the upper lip and nasal aperture with obliteration of the
      nasolabial fold and elevation of the nasal ala. A nasolabial cyst is described
      including its features on CT and MRI exams.

PMID- 20034825
TI  - Lithium citrate reduces excessive intra-cerebral N-acetyl aspartate in Canavan
      disease.
AB  - Our group has previously reported the first clinical application of lithium in a
      child affected by Canavan disease. In this study, we aimed to assess the effects
      of lithium on N-acetyl aspartate (NAA) as well as other end points in a larger
      cohort. Six patients with clinical, laboratory and genetic confirmation of
      Canavan disease were recruited and underwent treatment with lithium. The battery
      of safety and efficacy testing performed before and after sixty days of treatment
      included Gross Motor Function Testing (GMFM), Magnetic Resonance Imaging (MRI)
      Proton Magnetic Spectroscopy (H-MRS) as well as blood work. The medication was
      safe without any clinical or laboratory evidence for toxicity. Parental reports
      indicated improvement in alertness and social interactions. GMFM did not show
      statistically significant improvement in motor development. H-MRS documented an
      overall drop in NAA which was statistically significant in the basal ganglia. T1
      measurements recorded on MRI studies suggested a mild improvement in myelination
      in the frontal white matter after treatment. Diffusion Tensor Imaging was
      available in two patients and suggested micro-structural improvement in the
      corpus callosum. The results suggest that lithium administration may be
      beneficial in patients with Canavan disease.

PMID- 20034826
TI  - Pain and clinical findings in the low back: a study of industrial employees with
      5-, 10-, and 28-year follow-ups.
AB  - Little is known about the relationships of clinical findings in the low back with
      low back pain (LBP) in the normal working population. We studied whether
      physiotherapist's findings in the low back were associated with local and
      radiating LBP among a cohort (n=902) of employees in the engineering industry. A
      systematic non-proportional sample was drawn in strata by age, gender, and
      occupational class. The non-proportionality aimed at increasing sample size in
      smaller strata. Physiotherapists performed the straight-leg raising test (SRL),
      and made assessments of the fingertip-to-floor distance and pain in palpation of
      the lumbar interspinous spaces. The variables on pain at the interspinous spaces
      and the SRL tests were entered in cluster analysis. Three clusters emerged: no,
      minor, and severe clinical findings. In logistic regression analysis at baseline,
      limited forward flexion and the clinical findings cluster variable were
      associated with local and, particularly, radiating LBP. Follow-ups of the
      occurrence of local and radiating LBP at 5, 10, and 28 years from baseline were
      made. At the 5-year follow-up among subjects with no radiating LBP at baseline,
      the OR of radiating LBP for the clusters of minor and severe clinical findings
      compared to no findings were 2.7 (95% CI 1.4-5.1) and 3.8 (2.0-6.9),
      respectively, adjusted for age, gender, and occupational class. At the 10-year
      follow-up, the latter cluster predicted new reports of radiating LBP (1.9; 1.0
      3.1) and of local LBP (4.1; 1.9-9.0, among subjects with no local LBP at
      baseline), similarly adjusted. No associations between limited forward flexion
      and new cases of LBP were observed. Thus, membership in clusters with different
      levels of findings in simple clinical measurements predicted new reports of
      radiating LBP, in particular, among employees. The generalizability of the
      results may be limited due to the characteristics of the sampling.

PMID- 20034827
TI  - Radiation therapy for feline cutaneous squamous cell carcinoma using a
      hypofractionated protocol.
AB  - The objective of this paper was to evaluate the efficacy of a hypofractionated
      radiation protocol for feline facial squamous cell carcinoma (SCC). Twenty-five
      histologically confirmed SCCs in 15 cats were treated with four fractions of 7.6
      10Gy each, with 1 week intervals. The equipment used was a linear accelerator
      Clinac 2100 delivering electron beam of 4 or 6MeV, and a bolus of 5 or 10mm was
      used in all lesions. Of the lesions, 44% were staged as T4, 16% as T3, 8% as T2
      and 32% as T1. Of the irradiated lesions, 40% had complete response, 12% had
      partial response and 48% had no response (NR) to the treatment. For T1 tumors,
      62.5% had complete remission. Mean overall survival time was 224 days. Owners
      requested euthanasia of cats having NR to the treatment. Mean disease free time
      was 271 days. Side effects observed were skin erythema, epilation, ulceration and
      conjunctivitis, which were graded according to Veterinary Radiation Therapy
      Oncology Group (VRTOG) toxicity criteria. Response rates found in this study
      (52%) were lower when compared to other protocols, probably due to technique
      differences, such as fractionation schedule, bolus thickness and energy
      penetration depth. However, the hypofractionated radiation protocol was
      considered safe for feline facial SCC. Modifications of this protocol are being
      planned with the objective of improving the cure rates in the future.

PMID- 20034828
TI  - Dosimetric characterization of an 192Ir brachytherapy source with the Monte Carlo
      code PENELOPE.
AB  - Monte Carlo calculations are highly spread and settled practice to calculate
      brachytherapy sources dosimetric parameters. In this study, recommendations of
      the AAPM TG-43U1 report have been followed to characterize the Varisource VS2000
      (192)Ir high dose rate source, provided by Varian Oncology Systems. In order to
      obtain dosimetric parameters for this source, Monte Carlo calculations with
      PENELOPE code have been carried out. TG-43 formalism parameters have been
      presented, i.e., air kerma strength, dose rate constant, radial dose function and
      anisotropy function. Besides, a 2D Cartesian coordinates dose rate in water table
      has been calculated. These quantities are compared to this source reference data,
      finding results in good agreement with them. The data in the present study
      complement published data in the next aspects: (i) TG-43U1 recommendations are
      followed regarding to phantom ambient conditions and to uncertainty analysis,
      including statistical (type A) and systematic (type B) contributions; (ii)
      PENELOPE code is benchmarked for this source; (iii) Monte Carlo calculation
      methodology differs from that usually published in the way to estimate absorbed
      dose, leaving out the track-length estimator; (iv) the results of the present
      work comply with the most recent AAPM and ESTRO physics committee recommendations
      about Monte Carlo techniques, in regards to dose rate uncertainty values and
      established differences between our results and reference data. The results
      stated in this paper provide a complete parameter collection, which can be used
      for dosimetric calculations as well as a means of comparison with other datasets
      from this source.

PMID- 20034829
TI  - Stochastic modelling of the role of cisplatin in altered fractionation schedules
      for head and neck cancer.
AB  - Advanced head and neck cancers are one of the most challenging cancers facing the
      oncologists due to their aggressiveness attributable to the high hypoxic content
      and the tumour's ability to repopulate during radiotherapy. Alterations of
      radiotherapy fractionation schedules are possible ways to improve tumour control.
      Clinical trials have shown that both hyperfractionated radiotherapy (multiple
      fractions a day, over the same treatment time), and accelerated radiotherapy
      (higher doses per fraction, six days a week, over 5 weeks or less) are more
      effective than conventional radiotherapy in the management of head and neck
      cancer. However, the treatment choice between hyperfractionated and accelerated
      radiotherapy is still debated, due to very similar results obtained regarding
      tumour control. Furthermore, while radiotherapy alone has an impact on the short
      term prognosis of advanced head and neck cancer, the long-term benefits have been
      moderate. Cisplatin is a chemotherapeutic agent which combined with conventional
      radiotherapy has shown to improve patient survival. The present paper employs a
      Monte Carlo modelling approach in assessing the effect of combined cisplatin
      altered fractionation schedule on tumour response. The growth of a head and neck
      carcinoma has been modelled using probabilistic functions sampled by computer
      generated random number sequences, maintaining the biological constitution of a
      tumour. The tumour growth model has been built to simulate the in vivo processes
      taking place before and after radiotherapy/chemotherapy. The model has shown that
      adding cisplatin to radiotherapy improves tumour control in both
      hyperfractionated and accelerated radiotherapy.

PMID- 20034830
TI  - Reactive hemophagocytic lymphohistiocytosis and Crimean-Congo hemorrhagic fever.

PMID- 20034831
TI  - Cost-effectiveness model of using zoledronic acid once a year versus current
      treatment strategies in postmenopausal osteoporosis.
AB  - OBJECTIVES: To compare effectiveness, associated cost of outcomes and cost
      effectiveness of a single annual infusion of zoledronic acid versus current
      treatment strategies plans for postmenopausal osteoporosis in France. METHODS:
      Twelve simulation-based models were built to investigate three types of
      fractures: vertebral (VF), non-vertebral excluding hip (NVF) and hip (HF),
      comparing two groups: zoledronic acid and current postmenopausal antiosteoporotic
      treatment strategies. Two effectiveness comparability assumptions have been
      tested: specific agent efficacy values, and same standard efficacy values for all
      active agents. Direct medical costs included drug costs, medical visits,
      monitoring and fracture management. Adherence levels were integrated into the
      model under the assumption that non-adherent patients had treatment effects
      similar to the levels of placebo effectiveness. RESULTS: Using the most
      conservative assumption (same standard efficacy values for all active agents),
      zoledronic acid strategy results in less vertebral, non-vertebral and hip
      fractures than other current antiosteoporotic treatment options over 3 years:
      12.04% vs. 14.18%, 10.61% vs. 11.28% and 2.82% vs. 4.64% respectively, (p<0.001).
      In addition, zoledronic acid is more cost-effective than the current treatment
      strategies in all types of fractures (p<0.001): 1497 euros vs. 1685 euros per VF
      avoided, 1337 euros vs. 1404 euros per NVF avoided and 1216 euros vs. 1323 euros
      per HF avoided. CONCLUSION: Zoledronic acid is a cost-effective treatment
      strategy regardless of fracture type or effectiveness comparability assumptions.

PMID- 20034832
TI  - Prevalence and distribution of juvenile idiopathic arthritis in a region of
      Western France.
AB  - OBJECTIVE: To determine the prevalence and distribution of the various forms of
      juvenile idiopathic arthritis (JIA) in the Poitou-Charentes region of Western
      France. METHODS: We surveyed all the practicing rheumatologists and pediatricians
      in the study region for cases of JIA meeting ILAR criteria seen in 2006 among the
      population of 305,198 children younger than 16 years of age who resided in the
      study region. The survey was conducted by means of a questionnaire followed by a
      phone call. Cases of JIA identified by the survey were reviewed retrospectively.
      RESULTS: We identified 48 children with JIA, which yielded a prevalence of
      15.7/100,000. Mean age at diagnosis was 6.6 years (range, 1-15 years).
      Oligoarticular disease was the most common pattern, with 20 (41.6%) patients, a
      mean age of 4.9 years at diagnosis, and 80% of females. Oligoarticular disease
      was associated with the best outcomes, and only two (2/20, 10%) patients in this
      subgroup required disease-modifying therapy. Enthesitis-related arthritis
      contributed eight (16.6%) patients, with a mean age at diagnosis of 10.7 years
      and 75% of males. There were nine patients with polyarticular disease and seven
      with systemic disease; disease severity was greatest in these 16 patients, of
      whom only two were not taking disease-modifying drugs or glucocorticoids.
      CONCLUSION: The prevalence of JIA in Poitou-Charentes was similar to the
      prevalences reported in other regions of France.

PMID- 20034833
TI  - [Obstetrical management of women with previous caesarean section].
AB  - The authors announce their own experience and data of the literature to clarify
      their policy in cases of pregnancy after a previous caesarean section. For
      obstetricians, the question is to accept a trial of labor for vaginal birth or to
      decide an elective caesarean section. We particularly explain our conclusions in
      cases of breech deliveries, twin pregnancies, fetal pelvic disproportion,
      maternal diabetes, and labor inductions. In cases of previous caesarean, a trial
      of labor can be successfully tempted in numerous situations. Nevertheless, there
      are some limits not to be crossed.

PMID- 20034835
TI  - [A response by J.-C. Pasquier to the article be G. Kayem and F. Maillard: Preterm
      premature rupture of membranes: active or wait-and-see management?]].

PMID- 20034836
TI  - Sonochemical degradation of textile dyes in aqueous solution using sulphate
      radicals activated by immobilized cobalt ions.
AB  - Decolorisation of dye solutions by cobalt activated persulphate and
      ultrasonication has been investigated. Rhodamine B, Methylene Blue dye (basic
      dyes) and Acid orange II, Acid scarlet red 3R (acid dyes) were used as model
      compounds in this study. Immobilized cobalt ions, activated the persulphate to
      form highly reactive sulphate radicals. The degradation studies were conducted
      with only persulphate (PS), cobalt activated persulphate (PS+Co),
      persulphate+ultrasonication (PS+US) and cobalt activated
      persulphate+ultrasonication (PS+US+Co). The decolorisation efficiency were in the
      order of PS<PS+Co<PS+US<PS+US+Co for all the four dye solutions. The effect of
      pH, dosage of persulphate as well as catalyst and contact time was investigated.
      Under the optimum condition, the decolorisation obeyed first-order kinetics.
      Nearly 90-97% of decolorisation was achieved with COD and TOC removal of about 65
      73% and 53-62%, respectively, were achieved within an hour.

PMID- 20034837
TI  - Wall shear stress variations in a 90-degree bifurcation in 3D pulsating flows.
AB  - The exact role of fluid mechanics in the patho-physiological process of
      atherosclerosis has been a research topic over many years, yet without clear
      conclusive result. One has observed that morphological manifestations of the
      disease are found at some well-defined locations: certain vessel bifurcations and
      in curvatures. The flow in these regions is characterized by unsteadiness and
      often separation. Currently there are no complete theories that can explain the
      process since the different components in the process are not fully understood.
      Here we carry out detailed computations of the unsteady flow in an arterial
      segment typical to location of early appearance of arterial lesions. We study the
      wall shear stress (WSS) field variations near a junction with the purpose of
      identifying fluid-mechanical parameters that can be related to sites of
      atherosclerosis. The results show that regions associated with atherosclerosis
      experience highly elevated temporal- and spatial-derivatives of the WSS, also at
      less commonly known locations. Thus, large derivatives in time and space do not
      seem unique for the most common areas of atherosclerosis. Differences in WSS
      character between these locations are identified as differences in the time
      period of back flow as well as differences in the magnitude of the WSS
      derivatives. The data is presented in a way that facilitates understanding of the
      variations in WSS.

PMID- 20034838
TI  - Botulinum toxin type A in simple motor tics: short-term and long-term treatment
      effects.
AB  - To determine the short-term and long-term treatment-effects of botulinum toxin
      type A in simple motor tics, we analyzed 15 consecutive patients (18 tics) with
      simple motor tics that were treated every 3 months with injections of BTX-A.
      Efficacy (rated on a 4-level scale) and duration of effect of the first 2 and
      last 2 (if treated 5 times or more) treatments were recorded, as well as latency
      of response, changes of premonitory urges (PMUs) and possible side effects. Total
      number of treatments for each tic varied from 2 to 50 (mean 11, median 6). In 16
      of 18 tics (89%) short-term efficacy was reported successful (good or moderate).
      Long-term efficacy was reported in 12 tics of which 11 showed similar or even
      increased beneficial effects. Premonitory urge (PMU) was reported in 8 patients
      (53%). PMU, if present, lessened or disappeared after treatment with BTX-A. A
      permanent remission of the treated tic was seen in 3 patients with a maximum
      follow-up of 10 years. BTX-A appears a safe and effective treatment for simple
      motor tics and retains its efficacy after long-term treatment. BTX may also
      induce permanent remission of the treated tics and effects of BTX are not
      restricted to merely motor behaviour.

PMID- 20034839
TI  - Foreword.

PMID- 20034840
TI  - Some puzzles relating to the free-energy principle: comment on Friston.

PMID- 20034841
TI  - International rigid contact lens prescribing.
AB  - Rigid lenses have been fitted less since the introduction of soft lenses nearly
      40 years ago. Data that we have gathered from annual contact lens fitting surveys
      conducted in Australia, Canada, Japan, the Netherlands, Norway, the UK and the
      USA between 2000 and 2008 facilitate an accurate characterization of the pattern
      of the decline of rigid lens fitting during the first decade of this century.
      There is a trend for rigid lenses to be utilized primarily for refitting those
      patients who are already successful rigid lens wearers-most typically older
      females being refit with higher Dk materials. Rigid lenses are generally fitted
      on a full-time basis (four or more days of wear per week) without a planned
      replacement schedule. Orthokeratology is especially popular in the Netherlands,
      but is seldom prescribed in the other countries surveyed.

PMID- 20034842
TI  - Lipophilic versus hydrodynamic modes of uptake and release by contact lenses of
      active entities used in multipurpose solutions.
AB  - PURPOSE: To determine if the silicone-type components of new high Dk lens
      materials contribute significantly to uptake and/or release of two common
      antimicrobial agents, myristamidopropyl dimethylamine (Aldox) and
      poly[hexamethylene biguanide hydrochloride] (PHMB), found in multipurpose
      solutions. METHODS: Five commercial contact lenses were cycled in lens cases in a
      PHMB- and an Aldox-containing MPS. Single-cycle soaks (6, 16 or 64h) and multi
      cycle soaks (6, 16, 142 and 48h) were used to assess kinetics and saturation
      effects of uptake. Lens capacity for uptake of each entity was determined using a
      semi-saturation model. Release kinetics was assessed for these semi-saturated
      lenses (100-mL MPS-soaked) in 2mL of a tear mimic fluid. RESULTS: Lenses that
      exhibited low uptake in a single cycle (with 3mL of MPS) became saturated within
      approximately 3 cycles. PHMB uptake was highest with non-silicone hydrogel (non
      SiHy) and/or ionic lenses (approximately 70% depletion in 16h). PHMB uptake by
      non-ionic SiHy lenses was low (<40% depletion in a single 3-mL soak of 64h).
      Aldox uptake was highest for all SiHy lenses (approximately 80% depletion in
      16h). CONCLUSIONS: PHMB uptake capacity was highest by ionic and non-SiHy lenses,
      while Aldox uptake capacity was much higher with all SiHy lenses than with any
      non-SiHy lens. The slower desorption of PHMB (t(1/2)= approximately 120min)
      compared to Aldox (t(1/2)= approximately 20min) may partially explain observed
      higher staining after 2-4h with PHMB products used with some lenses, whereas any
      clinical effects from Aldox would be expected to manifest soon after insertion.

PMID- 20034843
TI  - The unraveling panoply of Francisella tularensis virulence attributes.
AB  - Francisella tularensis is a highly infectious Gram-negative bacterium causing the
      zoonotic disease tularemia. This facultative intracellular pathogen multiplies in
      vivo mainly inside macrophages, but has the capacity to infect and survive in
      many other cell types, including other phagocytic and nonphagocytic cells. In
      vitro, F. tularensis escapes rapidly from the phagosomal compartment and
      replicates in the cytoplasm of infected cells. An impressive number of novel
      genes related to F. tularensis pathogenesis have been identified recently.
      However, the information on biological functions still remains limited to a few
      of them. In this review, we will try to provide a comprehensive overview of the
      bacterial attributes, currently known-or suspected-to participate in F.
      tularensis virulence and will highlight the future challenges in F. tularensis
      research.

PMID- 20034844
TI  - DFT study of chemical mechanism of pre-SERS spectra in Pyrazine-metal complex and
      metal-Pyrazine-metal junction.
AB  - The chemical mechanism of Normal Raman Scattering (NRS) and pre-surface enhanced
      Raman scattering (pre-SERS) spectra for Pyrazine-Ag(2) complex, Ag(2)-Pyrazine
      Ag(2) junction and Ag(2)-Pyrazine-Au(2) junction were investigated with density
      functional theory (DFT) and charge difference densities (CDDs) for the first
      time. The NRS intensities of the above three structures enhanced obviously
      relative to isolated Pyrazine and the enhancement mechanism was confirmed to be
      static chemical enhancement. The pre-SERS intensities of the above three
      structures enhanced evidently compared to corresponding NRS intensities, and the
      enhancement mechanism was confirmed to charge transfer (CT) resonance Raman
      enhancement. The largest enhanced orders of NRS and pre-SERS intensities among
      the three structures were up to 10(3) and 10(5), respectively. Compared the
      intensity of pre-SERS with corresponding intensity of NRS spectra, the
      enhancement effect of Pyrazine-Ag(2) complex was larger than the others.
      Intramolecular and intermolecular CT on resonant electronic transition were
      described by CDDs.

PMID- 20034845
TI  - Study on cloud points of Triton X-100-cationic gemini surfactants mixtures: a
      spectroscopic approach.
AB  - This study investigates the effects of various cationic surfactants on the cloud
      point (CP) of the nonionic surfactant Triton X-100 (TX-100) in aqueous solutions.
      Instead of visual observation, a spectrophotometer was used for measurement of
      the cloud point temperatures. The values of CPs for Triton X-100 can be measured
      directly because TX-100 has an average number of oxyethylene units per molecule
      of p approximately 9.5 and a CP=66.0 degrees C. Quaternary ammonium dimeric
      surfactants (m-s-m, m=10, 12, and 16, and s=2, 6, and 10) were synthesized and
      used. The melting temperature T(M) and the Krafft temperature T(K) were measured
      for 1 wt% aqueous solutions of these synthesized surfactants. The melting
      temperature of the solid gemini surfactants increased with the carbon number of
      the alkyl chain. The results showed that additions of the gemini surfactants
      (which are infinitely miscible with water) to Triton X-100 increased the cloud
      point of the TX-100 solutions. All salts tested in these studies had a large
      effect on the CPs of nonionic surfactants due to their effect on water structure
      and their hydrophilicity. The effect of the alkyl chain length of the gemini
      surfactant on the CP of Triton X-100 is therefore more important than the spacer
      chain length.

PMID- 20034846
TI  - A Raman spectroscopic study of the mineral coquandite Sb6O8(SO4)x(H2O).
AB  - Raman spectra of coquandite Sb(6)O(8)(SO(4))x(H(2)O) were studied, and related to
      the structure of the mineral. Raman bands observed at 970, 990 and 1007 cm(-1)
      and a series of overlapping bands are observed at 1072, 1100, 1151 and 1217 cm(
      1) are assigned to the SO(4)(2-) nu(1) symmetric and nu(3) antisymmetric
      stretching modes respectively. Raman bands at 629, 638, 690, 751 and 787 cm(-1)
      are attributed to the SbO stretching vibrations. Raman bands at 600 and 610 cm(
      1) and at 429 and 459 cm(-1) are assigned to the SO(4)(2-) nu(4) and nu(2)
      bending modes. Raman bands at 359 and 375 cm(-1) are assigned to O-Sb-O bending
      modes. Multiple Raman bands for both SO(4)(2-) and SbO stretching vibrations
      support the concept of the non-equivalence of these units in the coquandite
      structure.

PMID- 20034847
TI  - Spectroscopic characterization of Cu(II) complex of L-phenylalanine and D,L
      tryptophan.
AB  - In this work, the reactions involving L-phenylalanine and D,L-tryptophan in the
      presence of Cu(II) ion were studied. Optimum conditions for the reactions were
      established as pH 7 and lambda=641 nm. When the reaction was kinetic, it was
      observed that the following rate formula was found as dA/A(n)=k dt and k=3.2 x
      10(-4)s(-1), according to absorbance measurements. Using a perpetual change
      curve, the ratio of [Cu]/[Cu]+L-phenylalanine+[D,L-tryptophan] was found 1:1:1.
      According to this result, one molecule of L-phenylalanine and one molecule of D,L
      tryptophan react with one molecule Cu(II) ion.

PMID- 20034848
TI  - Raman spectroscopic study of the antimonate mineral romeite.
AB  - Raman spectroscopy has been sued to study the antimony containing mineral romeite
      Ca(2)Sb(2)O(6)(OH,F,O) from three different origins. Romeite is a calcium
      antimonate mineral of the pyrochlore group. An intense Raman band at
      approximately 518 cm(-1) for romeite is assigned to the SbO nu(1) symmetric
      stretching mode and the band at 466 cm(-1) to the SbO nu(3) antisymmetric
      stretching mode. The Raman band at 303 cm(-1) is attributed to the OSbO bending
      mode. Some variation in band positions is observed and is attributed to the
      variation in composition between the three mineral samples.

PMID- 20034849
TI  - Studies on Cu(II) ternary complexes involving an aminopenicillin drug and
      imidazole containing ligands.
AB  - Equilibrium studies on the ternary complex systems involving ampicillin (amp) as
      ligand (A) and imidazole containing ligands viz., imidazole (Him), benzimidazole
      (Hbim), histamine (Hist) and histidine (His) as ligands (B) at 37 degrees C and
      I=0.15 mol dm(-3) (NaClO(4)) show the presence of CuABH, CuAB and CuAB(2). The
      proton in the CuABH species is attached to ligand A. In the ternary complexes the
      ligand, amp(A) binds the metal ion via amino nitrogen and carbonyl oxygen atom.
      The CuAB (B=Hist/His)/CuAB(2) (B=Him/Hbim) species have also been isolated and
      the analytical data confirmed its formation. Non-electrolytic behavior and
      monomeric type of chelates have been assessed from their low conductance and
      magnetic susceptibility values. The electronic and vibrational spectral results
      were interpreted to find the mode of binding of ligands to metal and geometry of
      the complexes. This is also supported by the g tensor values calculated from ESR
      spectra. The thermal behaviour of complexes were studied by TGA/DTA. The redox
      behavior of the complexes has been studied by cyclic voltammetry. The
      antimicrobial activity and CT DNA cleavage study of the complexes show higher
      activity for ternary complexes.

PMID- 20034850
TI  - Torquetenovirus viremia kinetics after autologous stem cell transplantation are
      predictable and may serve as a surrogate marker of functional immune
      reconstitution.
AB  - BACKGROUND: It is common experience that retreating patients too early after a
      course of intensive chemotherapy predisposes to opportunistic infections despite
      apparently normal lymphocyte levels. OBJECTIVES: The extent of replication of
      persistent viruses that cause no obvious disease (and hence need no treatment)
      might better define when a patient has recovered from functional immune
      deficiency. STUDY DESIGN: We used real-time polymerase chain reaction to monitor
      the kinetics of plasma torquetenovirus (TTV) viremia in hematological patients
      undergoing autologous hematopoietic stem cell transplantation as support to high
      dose chemotherapy (HSCT). RESULTS: Independently from underlying hematological
      disease and therapeutic regimen, TTV viremia increased post-HSCT, and this
      increase paralleled the increase of circulating CD8(+)CD57(+) T lymphocytes,
      known to represent an indirect marker of functional immune deficiency.
      Subsequently, within a matter of months, TTV levels returned to baseline values,
      at a pace that appeared to be constant over time. CONCLUSION: Monitoring of TTV
      viremia represents a unique opportunity to follow functional immune
      reconstitution in immunosuppressed patients. Also, the size of the TTV viremia
      increases resulting from immunosuppressive treatments might be of guidance in
      determining the appropriate time interval before delivery of a next course of
      therapy.

PMID- 20034851
TI  - Patterns of genetic diversity in the marine heterotrophic flagellate Oxyrrhis
      marina (Alveolata: Dinophyceae).
AB  - Oxyrrhis marina is an important model in ecological studies of free-living
      protists. Despite this, O. marina has rarely been studied in the environment and
      no explicit distributional studies exist. Further, phylogenetic data for a small
      number of isolates indicate that O. marina constitutes two divergent lineages.
      Here, we quantify phylogenetic variation between 58 globally distributed O.
      marina isolates using 5.8S--internal transcribed spacer 1 and 2 rDNA (5.8S ITS)
      and cytochrome c oxidase I (COI) partial sequences. 5.8S ITS and COI phylogenies
      both partitioned O. marina into four clades, which formed two lineages; mean
      sequence identity for 5.8S ITS and COI respectively was approximately 40 and 90%
      between these two lineages. Sequence identities for 5.8S ITS/ COI between clades
      within lineages were 66.3/99.4% (lineage 1: clade 1 vs 2) and 42.3/99.1% (lineage
      2: clade 3 vs 4). rDNA mutation rates in O. marina appear to be abnormally high
      and were not interpreted in a species delineation context. Based on variation in
      COI sequence and comparisons with other protists, we suggest that O. marina
      lineages may constitute two species. In a geographic context, evidence of spatial
      restriction but also extensive overlap between O. marina clades occurred.
      Further, clade abundances varied considerably: clades 1 and 2 (belonging to one
      lineage) were abundant and widespread; in contrast, clades 3 and 4 (belonging to
      the second lineage) were rare and spatially restricted (occurring only in the
      Mediterranean or in culture collection). There is need for further phylogenetic
      and taxonomic studies to assess species delineation in O. marina, and for the
      application of high resolution genetic markers to resolve processes driving
      genetic diversity in this important model organism.

PMID- 20034852
TI  - Ultrastructure and molecular phylogenetic position of a novel phagotrophic
      stramenopile from low oxygen environments: Rictus lutensis gen. et sp. nov.
      (Bicosoecida, incertae sedis).
AB  - A novel free free-living phagotrophic flagellate, Rictus lutensis gen. et sp.
      nov., with two heterodynamic flagella, a permanent cytostome and a cytopharynx
      was isolated from muddy, low oxygen coastal sediments in Cape Cod, MA, USA. We
      cultivated and characterized this flagellate with transmission electron
      microscopy, scanning electron microscopy and molecular phylogenetic analyses
      inferred from small subunit (SSU) rDNA sequences. These data demonstrated that
      this organism has the key ultrastructural characters of the Bicosoecida,
      including similar transitional zones and a similar overall flagellar apparatus
      consisting of an x fiber and an L-shape microtubular root 2 involved in food
      capture. Although the molecular phylogenetic analyses were concordant with the
      ultrastructural data in placing R. lutensis with the bicosoecid clade, the
      internal position of this relatively divergent sequence within the clade was not
      resolved. Therefore, we interpret R. lutensis gen. et sp. nov. as a novel
      bicosoecid incertae sedis.

PMID- 20034853
TI  - Inter-professional work based learning within an MSc in Advanced Practice:
      lessons from one UK higher education programme.
AB  - This paper will describe the implementation of inter-professional work based
      education (IPE) in one postgraduate Advanced Practitioner programme in the UK.
      The concept of Advanced Practice has developed as a response of a number of
      drivers including change in junior doctor training; government policy and
      increasing demands on the central government funded UK health service (the NHS).
      The programme was commissioned by the then greater Manchester Strategic Health
      Authority (now NHS North West) to meet service needs. The educational philosophy
      underpinning the MSc Advanced Practice (health and social care) provided by the
      University of Salford is IPE linked to work based learning. The process of work
      based learning (WBL) and inter-professional learning underpinning the programme
      will be discussed in relation to feedback from university staff, Advanced
      Practitioner (AP) students and employer feedback taken from programme and module
      evaluations. We argue that IPE at this level facilitates a greater understanding
      of the connectivity between professionals working in the health care system in
      the UK; a better understanding of the skills and knowledge base of colleagues;
      more inter-professional working and appropriate referrals in the work place. This
      has raised the profile of Advanced Practice (AP) in the region and ultimately
      resulted in better patient care with more effective and efficient use of
      resources (Acton Shapiro, 2006, 2008).

PMID- 20034854
TI  - ABO-mismatched platelet transfusions: strategies to mitigate patient exposure to
      naturally occurring hemolytic antibodies.
AB  - Clinically significant hemolysis is a rare but potentially severe complication of
      administering an ABO-mismatched platelet transfusion. Platelet products from
      Group O donors, particularly single donor platelets (SDP) are most commonly
      implicated in these reactions. This is due to the presence of unusually high
      titers of anti-A which can be found in the plasma of some Group O donors and the
      large plasma volume of SDPs. These products can cause significant hemolysis when
      infused into a Group A or AB recipient. Random donor platelets from Group O
      donors have also been implicated. In practice, platelets are frequently
      transfused across ABO barriers though, ideally, in order to prevent or mitigate
      these reactions, platelet transfusions that are matched for ABO should be
      administered. However, limited availability of donor platelets as well as an
      abundance of Group O donors makes this a difficult standard to adhere to since
      often out-of group products are the only ones available. Methods to improve the
      safety of Group O products have focused on defining a safe level of
      isohemagglutinins so that the risk of hemolysis is alleviated when mismatched
      products are transfused. Determining the critical titer which defines a level
      above which a mismatched product should not be administered has been challenging.
      Non-standardized methods of isohemagglutinin titering and varying reports in the
      literature where products with a wide range of titers have been implicated in
      acute hemolytic transfusion reactions have made it difficult to determine a cut
      off for labeling a product as high titer and thereby restricting its use to O
      recipients. Standards in the US place the responsibility for designing and
      implementing policies for the use of mismatched platelet products on each
      individual hospital transfusion service. Compliance requires only that there be
      an existing written policy which addresses the transfusion of products containing
      incompatible ABO antibodies but no specific procedures are required. In sharp
      contrast, European strategies have defined the low-end titer for which an out-of
      group transfusion should not be given to an ABO-incompatible recipient. This
      testing is performed centrally at the Blood Centers who then make the
      determination on the status of a "dangerous donor". The progress in this European
      strategy may serve the US to stimulate a re-examination of its practices and
      policies for the advancement of platelet transfusion safety.

PMID- 20034855
TI  - A human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats
      negatively regulates TLR7/9-mediated innate immune responses via selected TLR
      pathways.
AB  - A human microsatellite DNA-mimicking ODN (MS ODN) composed of CCT repeats,
      designated as SAT05f, has been studied for its capacity of negatively regulating
      innate immunity induced by TLR7/TLR9 agonists in vitro and in mice. The result
      showed that SAT05f could down-regulate TLR7/9-dependent IFN-alpha production in
      cultured human PBMC stimulated by inactivated Flu virus PR8 or HSV-1 or CpG ODN
      or imiquimod, protect d-GalN-treated mice from lethal shock induced by TLR9
      agonist, not by TLR3/4 agonist. In addition, SAT05f significantly inhibit IFN
      alpha production from purified human plasmacytoid cells (pDCs) stimulated by CpG
      ODN. Interestingly, SAT05f could up-regulate CD80, CD86, and HLA-DR on the pDCs
      in vitro, implying that SAT05f-mediated inhibition on IFN-alpha production could
      be related to the activation of pDCs. The data suggest that SAT05f could be
      developed as a candidate medicament for the treatment of TLR7/9 activation
      associated diseases by inhibiting TLR7/9 signaling pathways.

PMID- 20034856
TI  - Menstrual disturbances in puberty.
AB  - The most significant corporal change observed in adolescent girls is the onset of
      menstruation, which occurs between 12 and 13 years of age. In several cases,
      described with the term 'precocious puberty', pubertal development can begin at a
      significantly younger age. The term 'delayed puberty' refers to absence of
      pubertal development in a girl over the age of 14. Amenorrhoea can occur due to a
      broad spectrum of causes, such as anatomic deficiencies of the reproductive tract
      and hormonal disorders. Hypogonadotrophic hypogonadism, which implies a permanent
      malfunction in gonadotrophin secretion; hypergonadotrophic hypogonadism, which
      involves poor ovarian response in gonadotrophin stimulation; and
      hyperprolactinaemia can also lead to amenorrhoea. Significant amount of stress on
      the adolescent girl can cause hypothalamic dysfunction, leading to a situation
      called 'hypothalamic amenorrhoea'. Abnormal uterine bleeding (AUB), and
      especially the subtype of dysfunctional uterine bleeding (DUB), is the most
      urgent gynaecological problem during adolescence, while dysmenorrhoea (also
      referred to as painful menstruation) is the most frequent problem for which
      adolescents and their parents refer to a physician.

PMID- 20034857
TI  - Liquid chromatography tandem mass spectrometry applied to quantitation of the
      organophosphorus nerve agent VX in microdialysates from blood probes.
AB  - VX (O-ethyl-S-[2(di-isopropylamino)ethyl] methylphosphonothiolate) is a low
      volatility organophosphorus (OP) nerve agent and therefore the most likely route
      of exposure is via percutaneous absorption. Microdialysis has been used as a tool
      to study percutaneous poisoning by VX in the anesthetised guinea pig. A liquid
      chromatography tandem mass spectrometry (LC-MS-MS) method using positive
      electrospray ionisation (ESI) was used to quantitate VX in microdialysate samples
      collected from microdialysis probes, implanted into a blood vessel of
      anesthetised guinea pigs. The method resulted from modification of a LC-MS-MS
      method previously developed for the analysis of dermal microdialysates.
      Modification increased the sensitivity of the method, allowing quantitation of
      the trace levels of VX in blood microdialysates, over the range 0.002-1 ng/ml,
      with linear calibration. Quantitative results have been used to determine the
      time course of VX concentrations in the blood of guinea pigs following
      percutaneous poisoning.

PMID- 20034858
TI  - Improved method for the determination of cyclic guanosine monophosphate (cGMP) in
      human plasma by LC-MS/MS.
AB  - Cyclic guanosine monophosphate (cGMP) is an important second messenger molecule
      involved in gating ion channels and activating protein kinases. Here, we describe
      a validated LC-MS/MS method for the quantification of cGMP in human plasma,
      utilizing a stable isotope labeled analogue of cGMP as I.S. Plasma samples were
      extracted and concentrated by weak anion exchange solid phase extraction and the
      extracts were chromatographically separated on a porous graphitic carbon column.
      The analytes were detected by positive electrospray ionization and tandem mass
      spectrometry. The calibration function was linear in the range 1-20 nM and the
      intra- and inter-day precision showed relative standard deviations of better than
      2 and 6%, respectively. The accuracy was always better than 4%. Plasma
      concentrations in healthy human subjects determined with this method were 3.92+/
      1.17 nM (n=20). The method was, due to its isotope labeled I.S., matrix
      independent.

PMID- 20034859
TI  - Quantitative determination of formononetin and its metabolite in rat plasma after
      intravenous bolus administration by HPLC coupled with tandem mass spectrometry.
AB  - A new simple, rapid, sensitive and accurate quantitative detection method using
      liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for the
      measurement of formononetin (FMN) and daidzein (DZN) levels in rat plasma is
      described. Analytes were separated on a Supelco Discovery C18 (4.6x50 mm, 5.0
      microm) column with acetonitrile: methanol (50:50, v/v) and 0.1% acetic acid in
      the ratio of 90:10 (v/v) as a mobile phase. The method was proved to be accurate
      and precise at linearity range of 5-100 ng/mL with a correlation coefficient (r)
      of > or = 0.996. The intra- and inter-day assay precision ranged from 1.66-6.82%
      and 1.87-6.75%, respectively; and intra- and inter-day assay accuracy was between
      89.98-107.56% and 90.54-105.63%, respectively for both the analytes. The lowest
      quantitation limit for FMN and DZN was 5.0 ng/mL in 0.1 mL of rat plasma.
      Practical utility of this new LC-MS/MS method was demonstrated in a
      pharmacokinetic study in rats following intravenous administration of FMN.

PMID- 20034860
TI  - Ursodeoxycholic acid treatment in patients with cystic fibrosis at risk for liver
      disease.
AB  - BACKGROUND: Meconium ileus has been detected as a risk factor for development of
      liver disease in cystic fibrosis, with influence on morbidity and mortality.
      AIMS: To evaluate the effect of early treatment with ursodeoxycholic acid in
      patients with cystic fibrosis and meconium ileus to prevent chronic hepatic
      involvement and to explore the potential role of therapy on clinical outcomes.
      METHODS: 26 cystic fibrosis patients with meconium ileus (16 M, mean age 8,4
      years, range 3,5-9) were assigned to two groups: group 1 (14 patients) treated
      early with ursodeoxycholic acid (UDCAe); group 2 (12 patients) treated with
      ursodeoxycholic acid at the onset of cystic fibrosis liver disease (UDCAd).
      Anthropometric data, pulmonary function tests, pancreatic status, complications
      such as diabetes, hepatic involvement and Pseudomonas aeruginosa colonisation
      were compared among groups. RESULTS: A higher prevalence of cystic fibrosis
      chronic liver disease was observed in the UDCAd group with a statistically
      significant difference at 9 years of age (p<0.05). Chronic infection by P.
      aeruginosa was found in 7% of UDCAe and 33% of UDCAd (p<0.05). No differences
      were observed in nutritional status and other complications. CONCLUSIONS: Early
      treatment with ursodeoxycholic acid may be beneficial in patients at risk of
      developing cystic fibrosis chronic liver disease such as those with meconium
      ileus. Multicentre studies should be encouraged to confirm these data.

PMID- 20034861
TI  - Screening and early postnatal management strategies to prevent hazardous
      hyperbilirubinemia in newborns of 35 or more weeks of gestation.
AB  - Although kernicterus is a rare condition, it is still being reported in North
      America and Western Europe in addition to less developed parts of the world. The
      majority of affected infants are term and late-preterm newborns who have been
      discharged from the nursery as 'healthy newborns' yet have subsequently developed
      extreme hyperbilirubinemia and the classic neurodevelopmental findings associated
      with kernicterus. Published guidelines provide the basic tools for preventing
      hazardous hyperbilirubinemia and the two most important of these are a systematic
      assessment, prior to discharge, of each infant, for the risk of severe
      hyperbilirubinemia, and appropriate follow-up based on the time of discharge and
      the risk assessment. The most recent recommendations call for a predischarge
      measurement of the serum or transcutaneous bilirubin in all infants. When
      combined with the gestational age and other risk factors for hyperbilirubinemia,
      this provides the best estimate of the risk, or lack of risk, for subsequent
      hyperbilirubinemia, and determines the timing of follow-up and the need for
      further evaluation and treatment. The application of these principles to the
      management of the jaundiced newborn might not eliminate every case of
      kernicterus, but should contribute to a reduction in its occurrence.

PMID- 20034863
TI  - Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived
      cardiomyocytes.
AB  - Recent withdrawals of prescription drugs from clinical use because of unexpected
      side effects on the heart have highlighted the need for more reliable cardiac
      safety pharmacology assays. Block of the human Ether-a-go go Related Gene (hERG)
      ion channel in particular is associated with life-threatening arrhythmias, such
      as Torsade de Pointes (TdP). Here we investigated human cardiomyocytes derived
      from pluripotent (embryonic) stem cells (hESC) as a renewable, scalable, and
      reproducible system on which to base cardiac safety pharmacology assays. Analyses
      of extracellular field potentials in hESC-derived cardiomyocytes (hESC-CM) and
      generation of derivative field potential duration (FPD) values showed dose
      dependent responses for 12 cardiac and noncardiac drugs. Serum levels in patients
      of drugs with known effects on QT interval overlapped with prolonged FPD values
      derived from hESC-CM, as predicted. We thus propose hESC-CM FPD prolongation as a
      safety criterion for preclinical evaluation of new drugs in development. This is
      the first study in which dose responses of such a wide range of compounds on hESC
      CM have been generated and shown to be predictive of clinical effects. We propose
      that assays based on hESC-CM could complement or potentially replace some of the
      preclinical cardiac toxicity screening tests currently used for lead optimization
      and further development of new drugs.

PMID- 20034862
TI  - Transport disc distraction osteogenesis as an alternative protocol for mandibular
      reconstruction.

PMID- 20034865
TI  - [Mouse models of K-ras-initiated oncogenesis].
AB  - Activating mutations of the oncogene K-ras are found in one third of all human
      cancers. Much of our knowledge on K-ras signal transduction and its influence on
      tumor initiation and progression come from in vitro studies with cell lines.
      However, mouse models of human cancer allow a much more faithful recapitulation
      of the human disease, and the in vivo perspective is crucial for our
      understanding of neoplasia. In recent years, several new murine models for K-ras
      induced tumorigenesis have been described. They allow new insights into the
      specific role that oncogenic K-ras proteins play in different solid tumors, and
      they permit the molecular dissection of the pathways that are initiated by
      somatic mutations in subsets of cells. Key advances have been made by the use of
      tissue-specific and inducible control of expression, which is achieved by the
      Cre/loxP technology or the tetracycline system. From these sophisticated models,
      a common picture emerges: the effects of K-ras on tumor initiation depend
      strongly on the cellular context, and different tissues vary in their
      susceptibility to K-ras transformation.

PMID- 20034866
TI  - [Technical considerations for KRAS testing in colorectal cancer. The
      pathologist's point of view].
AB  - The KRAS status is now a mandatory prerequisite in order to treat metastatic
      colorectal patients with anti-EGFR (epidermal growth factor receptor) antibodies,
      such as cetuximab (Erbitux) or panitumumab (Vectibix). KRAS mutations are
      unambiguously linked to a lack of response to these targeted therapies and to a
      poor outcome. The optimal determination of the KRAS status should be based on
      coordination between pathologists and biologists. The pathologist must
      morphologically check the tumor to be analyzed and be sure that the fixatives
      used are valuable for molecular biology. The pathologist's involvement may also
      concern the DNA extraction and the KRAS mutations analyses. This involvement has
      to be included in a multidisciplinary setting in order to get rapid and robust
      tests for the clinical use. The imperative knowledge of the KRAS status in the
      management of metastatic disease represents a good example of this
      multidisciplinary coordination. In the future, the pathologist's role should be
      extended, considering the emergence of a more and more personalized medicine,
      integrating efficiency and cost-effectiveness. Thus, the pathologist may
      contribute to validate new molecular tests and to offer his specific techniques
      for translational research.

PMID- 20034867
TI  - [Prognostic role of KRAS mutation in colorectal cancer].
AB  - The management of patients with advanced or localized colorectal cancer (CRC)
      remains to date exclusively based on clinical, radiological and pathologic data.
      In CCR, KRAS mutations are detected in approximately 30-40% of tumours. In
      patients with a localized CRC, the prognostic role of KRAS mutation is not yet
      demonstrated with contradictory results in literature. For patients with
      metastatic CCR, KRAS mutations are a prognosis value for patients treated by anti
      EGFR antibody. Indeed, despite the use of monoclonal antibodies against epidermal
      growth factor receptor (EGFR) in metastatic CRC, the detection of molecular
      alterations in tumours is not integrated in the routine practice for patient
      decision-making. In patients treated with anti-EGFR Abs for a metastatic CRC, the
      detection of KRAS mutations on tumour DNA is now mandatory since several recent
      studies have clearly demonstrated that the presence of KRAS mutations confer a
      resistance to these therapies. Considering the lack of sufficient data, the
      detection of KRAS mutations is not recommended in other clinical setting.

PMID- 20034868
TI  - [Use of anti-EGFR antibodies (cetuximab and panitumumab) in the treatment of
      metastatic colorectal cancer in KRAS wild type patients].
AB  - Cetuximab and panitumumab are anti-EGF receptor antibodies, used in the treatment
      of colorectal cancer. Phase I and II studies have shown an interest in these
      molecules, after failure of chemotherapy combining 5-fluorouracil, folinic acid
      and oxaliplatin (Folfox) or irinotecan (IFL and Folfiri). Cetuximab with
      irinotecan has been approved by regulatory authorities following the results of a
      randomized phase II study where the combination arm (cetuximab-irinotecan) was
      superior to cetuximab alone. Retrospective studies have highlighted the impact of
      KRAS mutational status in the efficacy of EGFR antibodies. KRAS mutation is
      associated with a lack of response. Subgroup analysis of prospective studies have
      confirmed these hypothesis in first and second line metastatic treatment in
      combination with chemotherapy and in third line in monotherapy. At present
      cetuximab is approved in combination with chemotherapy in patients with non
      mutated KRAS metastatic colorectal cancer while panitumumab is only approved in
      monotherapy after failure of conventional chemotherapy.

PMID- 20034869
TI  - [Impact of mutational status of KRAS in the care of patients with colorectal
      cancer metastasis].
AB  - Colorectal cancer remains a leading cause of cancer deaths. Over the last decade,
      many new drugs have emerged in the treatment of metastatic colorectal cancers.
      Thus, significant progress has been achieved with daily use of oxaliplatin,
      irinotecan, or similar oral 5-fluorouracil (capecitabine or UFT). The
      identification of new molecular targets has allowed the development of new
      antitumor agents directed against receptors for growth factor or cons key factors
      involved in the process of angiogenesis. Large randomized trials of metastatic
      colorectal cancer have demonstrated significant clinical benefit with bevacizumab
      (inhibiting the vascular endothelial growth factor VEGF) and inhibitors of
      epidermal growth factor receptor (EGFR), namely cetuximab and the panitumumab. In
      this article, we review the role and impact of mutational status of KRAS in the
      care of patients with colorectal cancer metastasis.

PMID- 20034870
TI  - [Technical considerations for KRAS testing in colorectal cancer. The biologist's
      point of view].
AB  - Targeted therapy against the EGF receptor was shown to be effective in a subgroup
      of patients with KRAS wild-type colorectal cancer. Therefore, cetuximab (Erbitux)
      or panitumumab (Vectibix) obtained the authorization by the EMEA restricted to
      patients with KRAS wild-type tumours. KRAS mutational testing has become part of
      the standard care in patients treated with EGFR targeting therapy. Testing for
      KRAS mutations is not standardized, there is a multitude of methods, some of
      which are commercially available CE marked techniques. Most frequently used
      assays are developed in this review. It is very difficult today to tell which
      test is the most reliable. Moreover tumour samples are very heterogeneous
      (fixation, biopsy, surgical specimen, neoadjuvant treatment) and one "best"
      method could depend upon the type of sample. A STIC program is on going in France
      (MOKAECM) to initiate a quality assurance (QA)-program for KRAS testing. All INCa
      labelled laboratories that develop somatic oncology genetic tests participate to
      this program. Methods will be tested on cell line DNAs at first, then DNAs from
      paraffin embedded tumours will be shared and typed by the various laboratories.
      Finally, an economical evaluation will be done to compare techniques at all
      levels. This is of importance since KRAS testing needs to be done in a wide
      numbers of laboratories with similar value. KRAS testing is the first predictive
      genetic test in a frequent solid tumour, the establishment of a QA-program can
      serve as a future example for the introduction of other markers based on tumour
      genetic alterations.

PMID- 20034871
TI  - [Impact of KRAS in standard treatment of non-small cell lung cancer (NSCLC)
      patients in 2009: prognostic and predictive value].
AB  - The KRAS protein is known to play a key role in various oncogenic pathways. KRAS
      mutations are found in 20-30 % of patients with non-small cell lung cancer
      (NSCLC). The majority of mutations are found at KRAS codons 12 and 13, and they
      appear to be more frequent in smokers and adenocarcinoma. The mutated protein is
      in its active state despite absence of stimulation, which leads to the
      constitutive activation of downstream pathways responsible for cellular disorder.
      The identification of new biomarkers to predict the evolution of cancer
      pathogenesis (predictive factor) and the sensibility to treatments (predictive
      factor) is one of the major objectives in oncology research. KRAS mutations are a
      potential candidate biomarker and numerous studies have tried to confirm its
      place as a prognostic/predictive biomarker in NSCLC. The results are
      contradictory and most studies are retrospective. The first results of
      prospective studies are currently reported, in particular with the use of
      antibodies against EGFR. The exact place of KRAS in medical thoracic oncology
      remains to be determined and further studies are needed. To date, KRAS mutations
      are not a biomarker to be used routinely.

PMID- 20034872
TI  - [Targeting KRAS pathway in NSCLC therapy].
AB  - KRAS mutations are currently the most frequently mutated oncogenes in non-small
      cell lung cancers (NSCLC). A growing body of evidence suggests that targeting RAS
      could be an efficient strategy in NSCLC. Several approaches have been developed
      to target either RAS protein or downstream effectors such as RAF or MEK. First
      clinical trials evaluating farnesyltransferases inhibitors have led to
      unsuccessful results. However, targeting RAF and MEK could be a more efficient
      approach in NSCLC.

PMID- 20034873
TI  - [KRAS status versus EGFR status in lung cancer therapy].
AB  - Interest for development of molecular biomarkers tends to increase in clinical
      management of lung cancer. Indeed implementation in clinics of new molecules
      targeting epithelial growth factor (EGFR) such as erlotinib or gefitinib, rise
      several questions regarding the potential value of EGFR and KRAS mutations to
      predict therapeutic response. In the current review, we discuss the utilization
      of such biomarkers regarding published clinical data and the possibilities versus
      limitations associated with analyses performed in molecular laboratory on a daily
      setting basis.

PMID- 20034874
TI  - [Cutaneous side effects of EGF receptor inhibitors].
AB  - EGFR receptor inhibitors are used for the treatment of a number of solid tumors.
      Their cutaneous toxicity is a specific and frequent side effect that has shown to
      be correlated to the antitumoral effect. Here, we present an overview of the
      cutaneous manifestations and management of EGF receptor inhibitors toxicity.

PMID- 20034875
TI  - [Bone marrow stromal cells transfected with ciliary neurotrophic factor gene
      ameliorates the symptoms and inflammation in C57BL/6 mice with experimental
      allergic encephalomyelitis].
AB  - OBJECTIVE: To investigate the anti-inflammatory effect of bone marrow stromal
      cells (MSCs) transfected with recombinant adenovirus-mediated ciliary
      neurotrophic factor (CNTF) gene in C57BL/6 mice with experimental allergic
      encephalomyelitis (EAE). METHODS: An adenovirus vector containing CNTF gene Ad
      CNTF-IRES-GFP was constructed and transfected in the MSCs (MSC-CNTF). After
      examination of CNTF expression, the transfected cells were transplanted in
      C57BL/6 mice with MOG 35-55-induced EAE, which were monitored for the changes in
      the symptoms scores. The levels of tumor necrosis factor-alpha (TNF-alpha),
      inteferon-gamma (IFN-gamma), interleukin-12P35 (IL-12P35), and IL-10 in the
      peripheral blood of the mice were detected, and the number of MSC-CNTF cells in
      the spleen and spinal cord was counted. CD3+ T cell infiltration and TNF-alpha
      and IFN-gamma expressions in the lesions were also observed after the cell
      transplantation. RESULTS: CNTF gene transfection resulted in significantly
      increased CNTF expression in the MSCs. The mice receiving MSC-CNTF
      transplantation exhibited significantly improved symptoms with shortened disease
      course and lessened disease severity. The cell transplantation also resulted in
      significantly decreased peripheral blood TNF-alpha levels, ameliorated CD3+T cell
      infiltrations and lowered TNF-alpha expression in the lesions, while the levels
      of IFN-gamma underwent no significant changes. CONCLUSION: Transplantation of
      CNTF gene-transfected MSCs results in decreased peripheral blood TNF-alpha and
      IFN-gamma levels and reduced inflammatory cells, CD3-positive cells and TNF-alpha
      expression in the lesion of EAE, therefore providing better effect than MSCs in
      relieving the symptoms of EAE in mice.

PMID- 20034876
TI  - [A method for improving the accuracy and sensitivity of cell membrane
      chromatography].
AB  - OBJECTIVE: To improve the accuracy and sensitivity of cell membrane
      chromatography (CMC) and evaluate the feasibility of CMC in the study of subtype
      receptors. METHODS: Plasmids were used to transfer alpha(1B)-AR cDNA into human
      embryonic kidney 293 (HEK293) cell lines to obtain cell lines stably
      overexpressing the subtype receptors. HEK293 alpha(1B) cell membrane stationary
      phase (CMSP) was prepared by immobilizing the cell membrane on silica. The
      retention time of 9 alpha(1)-adrenoceptor ligands and capacity
      factors(kappa'(HEK293 alpha1B)) were calculated. The capacity factors of rat
      liver tissue and primary cultured rat hepatocytes were also calculated for a
      correlation analysis. RESULTS: The calculated capacity factors (kappa') were
      positively correlated to the published pKi values. The affinity rank orders were
      identical. The longest retention of the 9 alpha(1)-adrenoceptor ligands occurred
      on CMSP prepared with HEK293 alpha(1B) cell lines, while CMSP obtained from rat
      liver tissue showed the shortest retention of the ligands. CONCLUSION: CMC proves
      practical in the study of the subtype adrenoceptors. The accuracy and sensitivity
      of CMC can be improved using HEK293 alpha(1B) cell membrane.

PMID- 20034877
TI  - [Inhibitory effect of RNA interference targeting BaxBak on apoptosis of human
      granulosa cells].
AB  - OBJECTIVE: To investigate the inhibitory effect of small interfering RNA (siRNA)
      targeting Bax-Bak on the apoptosis of human granulosa cells. METHODS: Human
      granulosa cells were transfected with Bax-siRNA and Bak-siRNA either alone or in
      comibnation, and the cell morphological changes were obsered and the cell
      apoptosis was detected with flow cytometry. Western blotting was performed to
      examine the changes in Bax and Bak expressions in the transfected cells. RESULTS:
      Western blotting demonstrated significantly weakened expressions of Bax and Bak
      in the transfected cells. The cell morphology of the cells tranfected with Bak
      siRNA and with both Bak and Bax siRNA remained normal; the cells with exclusive
      Bax siRNA transfection presented with basically normal cell morphology, but black
      spots were noted in the cytoplasm. In the positive and negative control groups,
      the cells became rounded and shrank with expanded intercellular spaces and
      numerous black spots in the cytoplasm. Flow cytometry showed apoptotic indexes of
      3.44% and 3.97% in cells transfected with Bak siRNA and Bax-Bak siRNA,
      respectively, significantly lower than that in the negative group. Bax siRNA
      transfection resulted in an apoptotic index of 19.98%, similar to that in the
      negative group. CONCLUSION: Interference of the expression of Bak gene inhibits
      the apoptosis of human granulosa cells, and the inhibitory effect can be enhanced
      by simultaneous Bax interference, which, when used alone, does not obviosuly
      inhibit the apoptosis of human granulosa cells.

PMID- 20034878
TI  - [Cloning, expression and bioinformatic analysis of Rv3871 gene related to
      Mycobacterium tuberculosis virulent protein secretion].
AB  - OBJECTIVE: To clone and express the Rv3871 gene related to the virulent protein
      secretion of Mycobacterium tuberculosis and analyze its molecular structure,
      function and homology using bioinformatic approach. METHODS: A pair of primers
      was designed to amplify the Rv3871 gene, which was subcloned into the prokaryotic
      plasmid pET32a(+). The recombinant plasmid was identified by sequence analysis
      and the expressed recombinant protein by SDS-PAGE. The structure, function and
      homology alignment of Rv3871 were analyzed comparatively against other
      mycobacteria. RESULTS: The restriction fragments through molecular cloning
      matched perfectly in size with our prediction. The gene sequence was consistent
      with the corresponding sequence in GenBank. The expression protein was detected
      by SDS-PAGE with a molecular weight of 84 kD. Two FtsK/SpoE III domains were
      found by bioinformatic analysis. The homology results showed distinct differences
      between Rv3871 of the pathogenic M. tuberculosis and its counterparts in non
      pathogenic mycobacteria. CONCLUSION: Molecular cloning, expression and sequencing
      identify the structural and functional characteristics of Rv3871. The structural
      and functional differences of the gene between pathogenic and non-pathogenic
      mycobacteria identified by bioinformatics provide some evidence for the
      pathogenesis and drug targets of tuberculosis.

PMID- 20034880
TI  - [Cone-beam CT reconstruction based on circular scan trajectory and ring artifact
      reduction].
AB  - OBJECTIVE: The FDK algorithm is one of the most widely used algorithms for cone
      beam CT reconstruction in circular trajectory due to its simplicity of
      implementation and computational efficiency. However, the images reconstructed by
      the FDK algorithm based on real projection data may be blurred without electronic
      correction and geometric calibration, and are often plagued by deleterious ring
      artifacts and shading artifacts. We compared the images reconstructed with and
      without detector correction based on computer experiment of the real biological
      object. The experimental simulation shows that these algorithms are effective in
      reducing the ring artifact without compromising the image resolution, and produce
      satisfactory results.

PMID- 20034879
TI  - [Purification of E. coli invasin IbeA-binding protein in intestinal epithelial
      cells].
AB  - OBJECTIVE: To purify IbeA-binding protein from intestinal epithelial Caco-2
      cells. METHODS: Recombinant IbeA was purified, and 1, 5, and 10 microg/ml His
      IbeA and bovine serum albumin (control) were preincubated with confluent Caco-2
      monolayer for 30 min at 4degrees celsius;. Gentamicin protection assay was used
      to test the invasion of E. coli K1 pathogenic isolate E44 in Caco-2 cells. The
      binding proteins were purified from Caco-2 by IbeA-Cu(2+) sepharose affinity
      chromatography, and validated by Far-Western blotting. The N-terminal amino acid
      sequence of the binding protein was determined using Edman assay. RESULTS: E44
      invasion in Caco-2 cells was blocked by the recombinant IbeA in a dose-dependent
      manner. Two binding bands were obtained with His pull-down, and the binding
      specificity was demonstrated by Far-Western blotting. The N-terminal amino acid
      sequence of IBP200 was MASITKLP with an isoelectric point of about 5.0.
      CONCLUSION: Two novel Caco-2 proteins interacting with IbeA of E. coli have been
      purified and identified.

PMID- 20034881
TI  - [Identification of the interactions between the truncated fragments of macrophage
      migration inhibitory factor and CD74 using a yeast two-hybrid system].
AB  - OBJECTIVE: To investigate the interaction domains between macrophage migration
      inhibitory factors (MIF) and the extracellular segment of type-II trans-membrane
      protein CD74 using a yeast two-hybrid system. METHODS: By using molecular cloning
      techniques, the DNA fragments encoding MIF, MIF(50-65) and MIF(1-50/65-115) were
      introduced into the pGBKT7 vector to construct the corresponding recombinant bait
      plasmids, and the DNA fragments encoding CD74(73-232), CD74(73-109), CD74(1109
      149) and CD74(149-232) into the pGADT7 vector to construct the recombinant
      activation domain (AD) plasmids. PEG/LiAC method was employed to transform the
      above 3 recombinant bait plasmids paired with each of the 4 recombinant AD
      plasmids into the chemical competent yeast AH109 cells. The transformed yeast
      AH109 cells were screened consecutively on SD/-Trp-Leu and SD/-Trp-Leu-Ade-His/X
      alpha-gal nutritional media. RESULTS: The results of restriction endonuclease
      digestion and DNA sequencing verified the correct construction of all the
      recombinant plasmids. The yeast AH109 cells transformed with each of the 3
      recombinant bait plasmids could grow on SD/-trp nutritional media without
      autonomous activation effect on the reporter gene MEL1. The cells transformed
      with each of the 4 recombinant AD plasmids could also grow on SD/-leu nutritional
      media without activation of the reporter gene MEL1. Only the yeast AH109 cells co
      transformed with MIF, MIF(50-65), or MIF(1-50/65-115) plasmid and CD74(73-232)
      plasmid could grow on SD/-Trp-Leu-Ade-His nutritional media with transcription
      activation of the reporter gene MEL1. CONCLUSION: MIF interacts with the intact
      extracellular segment of CD74 (CD74(73-232)) independent of the functional domain
      of MIF(50-65).

PMID- 20034882
TI  - [Absorption characteristics of ginsenoside Rb2 in Caco-2 cell monolayer].
AB  - OBJECTIVE: To determine the concentration of ginsenoside Rb(2) and study the
      absorption characteristics of ginsenoside Rb(2) in Caco-2 cell monolayer.
      METHODS: LC-MS-MS was used to determine the concentration of ginsenoside Rb(2),
      and the apparent permeability coefficient (P(app)) of ginsenoside Rb(2) was
      calculated. RESULTS: P(app(AP-BL)) was 3.27 x 10(-7) cm.s(-1), P(app(BL-AP)) was
      3.16 x 10(-6) cm.s(-1), and the efflux ratio (P(app(BL-AP))/P(app(AP-BL))) was
      9.63. CONCLUSION: The absorption characteristics of ginsenoside Rb(2) in Caco-2
      cell model have been demonstrated.

PMID- 20034883
TI  - [Bone marrow stem cell-derived astrocytes are involved in glia limitans formation
      in rats after brain injury].
AB  - OBJECTIVE: To investigate the involvement of bone marrow stem cell-derived
      astrocytes (BMDSCs) in the formation of glia limitans after brain injury.
      METHODS: In a female SD rat model of brain injury, green fluorescence protein
      (GFP)-labeled BMDSCs from male SD rats were transplanted via the caudal vein 24 h
      after the injury. The rats were sacrificed at 2, 4 and 8 weeks after the
      transplantation, and immunohistochemistry for glial fibrillary acidic protein
      (GFAP) was performed to observe the astrocytes. The fluorescence emitted by GFP
      was observed to identify the presence of the bone marrow-derived stem cells, and
      the GFAP(+)/GFP(+) cells in the glia limitnas were detected under fluorescence
      microscopy. RESULTS The GFAP(+)/GFP(+) cells were found in the glia limitans
      between the brain lesion and normal brain tissue. CONCLUSION: Bone marrow stem
      cell-derived astrocytes is involved in glia limitans formation after brain
      injury, which can be of significance in brain injury recovery and implantation of
      engineered materials.

PMID- 20034884
TI  - [Screening of proteins binding to FXR1P using yeast two-hybrid technique].
AB  - OBJECTIVE: To screen the proteins interacting with FXR1P for functional
      investigation of FXR1P. METHODS: The yeast strain AH109 transformed with the
      recombinant expression vector pGBKT7/FXR1 was mated with the yeast strain Y187
      pretransformed with human fetal brain cDNA library. The positive clones were
      screened and identified by sequence analysis. RESULTS: The recombinant expression
      vector pGBKT7/FXR1 was constructed successfully. Five proteins binding to FXR1P
      were screened from human fetal brain cDNA library using the yeast two-hybrid
      system, including CMAS, FTH1, GOLGA4, HSD17B1 and CSH1. CONCLUSIONS: These
      results provide new clues for investigating the biological functions of FXR1P and
      the pathogenesis of Fragile X syndrome.

PMID- 20034885
TI  - [Clinical and pathological analysis of 8 hereditary nonpolyposis colorectal
      cancer pedigrees].
AB  - OBJECTIVE: To analyze the clinical and pathological features of patients with
      hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: The data of 8 HNPCC
      pedigrees according with Amsterdam standard II were collected and their pedigree
      trees were generated. RESULTS: The morbidity of HNPCC was 1.59%. Thirty-one
      patients were found in the 8 HNPCC pedigrees including 25 with colorectal cancer
      and 6 with extraintestinal tumors. The 8 probands consisted of 6 female and 2
      male patients, among whom 4 were younger than 40 years old, 2 had lesions in the
      right colon, 3 in the left colon, and 3 in the rectum. The tumors were
      histologically identified mainly as highly to moderately differentiated
      adenocarcinoma; all the patients were free of lymph node or distant metastasis.
      Of the 8 probands, 5 had abnormal expression of MMR protein and only 1 had normal
      expression. CONCLUSION: The HNPCC probands are characterized by early onset at a
      young age and high differentiation of the tumor. The members of the pedigrees
      show a high incidence of the malignancies, and regular examination and timely
      treatment can be effective in preventing the tumor occurrence and reducing the
      mortality. Detection of MMR gene mutation can be a crucial approach to raising
      the diagnostic rate of HNPCC.

PMID- 20034886
TI  - [Anesthetic management during cardiac bypass in fetal lambs].
AB  - OBJECTIVE: To summarize the anesthetic management in fetal lamb cardiac bypass.
      METHODS: Five ewes at 120-140 days of gestation were anesthetized intramuscularly
      with katamine hydrochloride, intubated and ventilated with a respirator.
      Anesthesia was maintained with fentanyl and vecuronium. Lactated Ringer's
      solution and magnesium sulfate were infused to maintain the mean blood pressure
      (MAP) over 70 mmHg and uterine relaxation. The fetal lambs received anesthesia
      with fentanyl and vecuronium intramuscularly via the uterine wall. Fetal cardiac
      bypass was established with pulmonary artery and right atrium cannulation,
      lasting for 30 min. The hemodynamic and blood gas data of the ewes and fetal
      lambs were recorded before bypass, at 30 min during bypass, and at 1 and 2 h
      after cessation of bypass. The pulse index of the umbilical artery (PIua) and the
      ewe's uterine artery (PIeu) were monitored simultaneously. RESULTS: The MAP and
      heart rate (HR) of the fetus remained normal during the anesthesia. PIua
      increased significantly after cessation of bypass (P<0.05). Although the fetal
      oxygen tension in the axillary artery remained normal, the fetal lambs showed
      hypercarbia and acidosis after cessation of bypass (P<0.05). The maternal MAP and
      HR remained normal. The PIeu decreased significantly during bypass (P<0.05) and
      recovered the normal level after cessation of bypass. The arterial blood gas of
      the ewes was normal during the experiment. CONCLUSION: Maintaining high
      hemodynamics in the ewes, application of uterine relaxation and intensive care
      during anesthesia are crucial in anesthetic management of cardiac bypass in fetal
      lambs.

PMID- 20034887
TI  - [Inhibitory effect of dexamethasone on myeloid differentiation factor 88 and
      tumor necrosis factor-alpha expressions in mouse peritoneal macrophages].
AB  - OBJECTIVE: To study the inhibitory effect of dexamethasone (DEX) on myeloid
      differentiation factor 88 (MyD88) and tumor necrosis factor-alpha (TNF-alpha)
      expression in mouse peritoneal macrophages in innate immune response to
      Penicillium marneffei (PM). METHODS: Mouse peritoneal macrophages were cultured
      in the presence of heat-inactivated yeast-phase PM with or without DEX, and the
      protein and mRNA expressions of MyD88 in the macrophages were detected using
      Western blotting and real-time PCR, respectively. TNF-alpha in the cell culture
      supernatant was measured with enzyme-linked immunosorbent assay. RESULTS: DEX
      suppressed TNF-alpha production by the macrophages co-cultured with PM. The
      expressions of MyD88 were up-regulated by PM stimulation, whose effect was
      inhibited by the application of DEX. CONCLUSION: The inhibitory effect of DEX on
      PM-induced proinflammatory responses of the macrophage is directly associated
      with the inhibition of MyD88 expression.

PMID- 20034888
TI  - [Construction of mic2/CD99 gene vector and its transfection in Hodgkin lymphoma
      L428 cell line].
AB  - OBJECTIVE: To construct a eukaryotic expression vector of CD99 gene for
      transfection into Hodgkin lymphoma L428 cells. METHODS: The full-length cDNA of
      CD99 gene was amplified from Jurkat cells by RT-PCR and cloned into the
      pcDNA3.1(+) vector and transfected into L428 cell line using Lipofextamine 2000.
      The sequence of CD99 mRNA in the transfected cells was confirmed by restriction
      endonuclease digestion and DNA sequencing, and the expression of CD99 protein was
      identified using immunocytochemistry. RESULTS: A gene fragment of 558 bp was
      amplified from the transfected cells and the sequence was verified by DNA
      sequencing. Immunocytochemistry identified the presence of CD99 expression in the
      transfected cells. CONCLUSION: A eukaryotic expression vector pcDNA3.1(+)-CD99 is
      successfully constructed and stably expressed in L428 cell line.

PMID- 20034889
TI  - [Effect of glial cell metabolism on respiratory rhythmical discharge activity in
      neonatal rat medulla oblongata slices].
AB  - OBJECTIVE: To explore the role of glial cell metabolism in the generation and
      regulation of central respiratory rhythm. METHODS: The medulla oblongata slices
      (600-700 microm) containing the medial region of the nucleus retrofacialis (mNRF)
      with the hypoglossal nerve rootlets retained from 12 neonatal (0-3 days) Sprague
      Dawley rats were prepared and perfused with modified Kreb's solution (MKS). Upon
      recording of respiratory rhythmical discharge activity (RRDA) of the rootlets of
      the hypoglossal nerve, the brain slices were treated with glial cell metabolism
      antagonist L-methionine sulfoximine (L-MSO, 50 micromol/L) for 20 min followed by
      application of glial cell metabolism agonist L-glutamine (L-GLN, 30 micromol/L)
      for 20 min, or with L-MSO for 20 min with additional L-GLN for 20 min. The
      changes in the RRDA of the rootlets of the hypoglossal nerve in response to the
      treatments were recorded. RESULTS: L-MSO prolonged the respiratory cycle (RC) and
      expiratory time (TE), and reduced the integral amplitude (IA) and the inspiratory
      time (TI) in the brain slices. L-GLN induced a significant decrease in RC and TE,
      but IA and TI showed no obvious variations. The effect of L-MSO on the
      respiratory rhythm was reversed by the application of L-GLN. CONCLUSION: Glial
      cell metabolism may play an important role in the modulation of RRDA in neonatal
      rat brainstem.

PMID- 20034890
TI  - [Construction and identification of the recombinant adenovirus expressing the
      short hairpin RNA targeting phosphatase and tensin homolog deleted on chromosome
      ten gene].
AB  - OBJECTIVE: To construct the recombinant adenovirus expression vector of a short
      hairpin RNA (shRNA) targeting phosphatase and tensin homolog deleted on
      chromosome ten (PTEN) gene for gene therapy of ischemic cerebral injury. METHODS:
      The U6 expression promoter and shRNA of pGenesil-1-shRNA, which was constructed
      and identified in our previous experiment, were subcloned to pAdTrack shuttle
      plasmid. The product pAdTrack-U6-shRNA was linearized by PmeI for homologous
      recombination with pAdEasy-1 in pAdEasy-1 competence bacteria. The positive clone
      was identified by enzyme digestion, PCR analysis and DNA sequence analysis. After
      linearization by PacI, the recombinant adenovirus DNA shuttle plasmid pAdEasy-U6
      shRNA was transfected into 293 cells for packaging and amplification of Ad-U6
      shRNA, which was further identified by PCR analysis and DNA sequence analysis.
      Western blotting was used to detect the expression of PTEN protein in the
      hippocampal neurons infected with the adenovirus. RESULTS: The pAdTrack-U6-shRNA
      and pAd-U6-shRNA plasmids had been successfully constructed as verified by PCR
      analysis, enzyme digestion and DNA sequence analysis. PCR analysis and DNA
      sequence analysis confirmed successful packaging of the recombinant adenovirus Ad
      U6-shRNA in 293 cells. PTEN protein expression decreased significantly in the
      hippocampal neurons after infection by the recombinant virus. CONCLUSION: We have
      successfully constructed the recombinant adenovirus Ad-U6-shRNA targeting PTEN
      gene, which provides a basis for investigating the role of PTEN in
      neuroprotection after cerebral ischemic injury using RNA interference.

PMID- 20034891
TI  - [Analysis of the risk factors of community-acquired pneumonia in patients with
      primary Sjogren's syndrome].
AB  - OBJECTIVE: To investigate the risk factors of community-acquired pneumonia (CAP)
      in patients with primary Sjogren's syndrome (pSS). METHODS: The clinical data
      were collected from 121 inpatients with pSS and univariate analysis and logistic
      regression were conducted to analyze the risk factors of CAP. RESULTS: The
      incidence of CAP in the 121 patients with pSS was 27.3%. Age, disease course, low
      while blood cells, low complement levels, liver and kidney dysfunction, low
      albumin, hyperglobulinaemia, renal tubule acidosis, interstitial lung disease
      (ILD) and immunosuppressive agents were closely related to CAP in these patients.
      Logistic regression analysis identified ILD, low complement levels and
      hyperglobulinemia as the risk factors for CAP in patients with pSS. CONCLUSION:
      Vigorous control of pSS and minimizing the risk factors may prove effective to
      lower the incidence of CAP in patients with pSS.

PMID- 20034892
TI  - [Effects of Wulongdan on learning and memory abilities of rats with chronic
      cerebral ischemia].
AB  - OBJECTIVE: To evaluate the effect of Wulongdan, a tradition Chinese medicinal
      preparation, on the learning and memory abilities of rats with chronic cerebral
      ischemia and explore the mechanisms. METHODS: Male rats with chronic cerebral
      ischemia induced by permanent ligation of the bilateral carotid arteries were
      randomized into sham-operated group, chronic cerebral ischemia (model) group, and
      high-, middle-, and low-dose Wulongdan groups and Yinxingye group. The
      corresponding treatments were administered in the rats 24 h after the operation
      once daily for 8 consecutive weeks. Morris water maze and step-through tests were
      performed after 7 weeks of drug administration. The brain tissues were then taken
      to observe the morphological changes in the hippocampal neurons with Nissl
      staining by transmission electron microscopy. RESULTS: Compared with the model
      group, the latency of finding the platform in Morris water maze test was
      significantly shortened (P<0.05 or 0.01), and that in step-through test
      significantly prolonged (P<0.05 or 0.01) in high-, middle-, and low-dose
      Wulongdan groups and Yinxingye group. In the model group, Nissl staining of the
      hippocampal CA1 region visualized obvious pathological changes in the neurons,
      showing a significant difference from the sham-operated and high-dose Wulongdan
      groups. CONCLUSION: Wulongdan can enhance the learning and memory abilities of
      rats with chronic cerebral ischemia possibly through a mechanism in relation to
      neuronal protection in the hippocampus CA1 region.

PMID- 20034893
TI  - [Radiosynthesis of peripheral benzodiazepine receptor radioligand [N-methyl
      (11)C]PK 11195 as an imaging agent for positron emission tomography].
AB  - OBJECTIVE: To establish a protocol of automated synthesis of 1-(2-chlorophenyl)-N
      [(11)C]methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide ((11)C-PK11195) as
      the positron-emitter-labeled ligand for peripheral benzodiazepine receptor (PBR)
      using a commercial synthesizer and explore the quality control methods for the
      resulting product. METHODS: (11)C-methyl iodide ((11)C-CH(3)I) was synthesized
      via liquid-phase distillation approach using a (11)C-iodomethane synthesizer.
      (11)C-PK11195 was prepared by (11)C-methylation of 1-(2-chlorophenyl)-N-(1
      methylpropyl)-3-isoquinoline carboxamide (N-demethyl-PK 11195) as the precursor
      with (11)C-CH(3)I and purified by semi-preparative reversed phase high
      performance liquid chromatography (HPLC). The radiochemical purity, chemical
      purity and stability of the product were evaluated by HPLC, and the toxicity was
      assessed in normal mice. The factors that affected (11)C-PK11195 synthesis were
      also studied. RESULTS: (11)C-PK11195 was successfully synthesized using the
      TracerLab FX(F-N) synthesizer. The synthesis time was about 35 min from the end
      of (11)C-carbon dioxide production by cyclotron to the end of (11)C-PK11195
      synthesis (EOS), with a (11)C-methylation reaction time of 3-4 min. The
      uncorrected radiochemical yield for (11)C-methylation was (33-/+5)%. Analysis
      with radio-analytical HPLC showed a radiochemical purity and chemical purity of
      the product both exceeding 99%, with a specific radioactivity of 30-65
      GBq/micromol at EOS (from the end of radionuclide production). The (11)C-PK11195
      synthesized was radiochemically stable at room temperature and showed low
      toxicity in normal mice. CONCLUSION: The (11)C-PK11195 injection can be
      conveniently prepared using an automated synthesizer for clinical use in positron
      emission tomography.

PMID- 20034894
TI  - [Protective effect of preconditioning with PEP-1-CAT fusion protein against
      myocardial ischemia-reperfusion injury in rats].
AB  - OBJECTIVE: To investigate the transduction efficiency of purified PEP-1-CAT
      fusion protein into rat heart and the protective effect of the fusion protein
      against myocardial ischemia-reperfusion injury. METHODS: PEP-1-CAT or CAT (500
      microg) was injected in SD rats via the caudal vein, using normal saline as the
      control, and the hearts were harvested at 0.5, 1, 2, 4, 8, and 24 h after the
      injection. The transduction efficiency was evaluated by immunofluorescence
      technique, and the CAT activity was measured. Forty rats were randomized into 5
      groups, namely the sham-operated group, ischemia-reperfusion group, and 3 PEP-1
      CAT -treated groups (100, 300, and 500 microg). The left main coronary artery was
      occluded for 1 h followed by a 2-h reperfusion, and at the end of reperfusion,
      serum LDH and CK and MDA content in the myocardium were measured. RESULTS: No
      green fluorescence was observed in saline group or CAT group. Bright green
      fluorescence was observed in PEP-1-CAT groups at different time points, most
      conspicuous at 8 h. No significant difference in CAT activity was found between
      CAT group and saline group (P>0.05); with the lapse of time, CAT activity in PEP
      1-CAT group increased gradually, reaching the peak level at 8 h, which was 4.2
      folds of that in the saline group. LDH ,CK and MDA were significantly lower in
      PEP-1-CAT- groups than in ischemia-reperfusion group (P<0.01). CONCLUSION: PEP-1
      can mediate the transduction of CAT in rat heart in a time-dependent manner, and
      PEP-1-CAT preconditioning provides a protective effect against ischemia-
      reperfusion injury in rats.

PMID- 20034895
TI  - [Effects of irbesartan on renal advanced glycation end products and their
      receptor in rats with early diabetic nephropathy].
AB  - OBJECTIVE: To investigate the effect of irbesartan on the renal expressions of
      advanced glycation end products (AGEs) and their receptor (RAGEs) in rats with
      early diabetic nephropathy (DN) and the renoprotection mechanism of irbesartan.
      METHODS: Rat DN models established by a single injection of streptozotocin were
      randomly divided into the model group and irbesartan treatment group. With normal
      rats as the control, all the rats received daily gavage for 8 weeks. The 24-h
      urinary protein excretion and contents of AGEs in the serum and kidney tissues
      were measured. The expressions of RAGEs and RAGEs protein and mRNA in the kidney
      tissues were detected by immunohistochemistry and reverse transcription
      polymerase chain reaction, respectively. The pathological changes of the kidney
      were also assessed microscopically. RESULTS: Irbesartan significantly reduced the
      24-h urinary protein excretion and the contents of AGEs in the serum and kidney
      tissues of DN rats, resulting also in decreased expressions of RAGEs and RAGEs
      protein and mRNA levels in the kidney. The treatment obviously alleviated the
      pathological changes in the kidney of the DN rats. CONCLUSION: Irbesartan offers
      renoprotection against DN possibly by reducing the serum and renal contents of
      AGEs and inhibiting the renal mRNA expressions of RAGEs and RAGEs.

PMID- 20034896
TI  - [Analysis of the clinical manifestations and electrophysiological changes in 32
      patients with atypical myasthenia gravis].
AB  - OBJECTIVE: To study the clinical characteristics and electrophysiological changes
      in patients with atypical myasthenia gravis (MG). METHODS: The characteristics of
      the clinical symptoms and electrophysiological changes were investigated in 32
      patients with atypical MG diagnosed in our hospital from January 2004 to December
      2008. RESULTS: The ages of the patients ranged from 7 to 70 years. Five patients
      were diagnosed to have ocular MG (OMG), among whom 2 patient only complained of
      eye discomfort and blurred vision. Twenty-seven patients had generalized MG, and
      6 of them showed muscle weakness of the limbs with or without mild difficulty in
      swallowing or respiratory muscles, but free of muscle dysfunctions in muscles of
      eyes, head, neck or face. Another 2 patients manifested muscular atrophy. Twenty
      three patients (71.9%) displayed both fluctuating symptoms and positive results
      of fatigue test. Twenty-nine patients (90.6%) have positive results in the
      neostigmine test. Two patients in the OMG group (40.0%) showed positive results
      in the low frequency repetitive nerve stimulation (LFRNS), as compared with the
      21 patients in the generalized MG group (71.9%) showing positive results. The
      total positivity rate of LFRNS was 71.9% in the total patients, consistent with
      the published data. CONCLUSIONS: In MG patients with atypical clinical symptoms,
      negative results of neostigmine test and fatigue test, LFRNS test can be an
      indispensable method to increase detection rate of MG and reduce erroneous or
      missed diagnosis.

PMID- 20034897
TI  - [Proton magnetic resonance spectroscopy of the thalamus and hypothalamus in
      patients with first-episode depression].
AB  - OBJECTIVE: To investigate the presence of abnormal metabolism in the thalamus and
      hypothalamus in patients with first-episode depression. METHODS: Thirty drug
      naive patients with first-episode depression and 30 age-matched controls were
      scanned with proton magnetic resonance spectroscopy ((1)H-MRS) for Naa, Cho, Cr
      and mI. RESULTS: Compared with the control group, the patients showed
      significantly reduced mI and mI/Cr of the hypothalamus, reduced mI/Cr of the left
      thalamus, and lowered Cho, ml, and ml/Cr of the right thalamus (P<0.05).
      CONCLUSION: Patients with first-episode depression may have myo-inositol and
      phosphoric acid metabolism disorder in the thalamus and hypothalamus with
      malfunction of cellular osmotic pressure adjustment mechanism. Abnormal mI/Cr in
      the thalamus and hypothalamus may represent an important biochemical change in
      advanced patients with depression.

PMID- 20034898
TI  - [Protective effect of pentoxifylline on acute pulmonary injury after one-lung
      ventilation in rabbits].
AB  - OBJECTIVE: To investigate the effect of pentoxifylline on one-lung ventilation
      injury in rabbits. METHODS: Twenty rabbit models of one-lung ventilation by
      intrabronchial intubation after tracheotomy were randomly allocated in control
      group (with one-lung ventilation) and experiment group (with one-lung ventilation
      and intravenous pentoxifylline administration). One-lung ventilation was
      maintained for 3 h in both groups using the volume-control mode (tidal volume of
      8 ml/kg at the frequency of 30 per min). Arterial blood samples were taken after
      anesthesia and at 3 h of one-lung ventilation for arterial blood gas analysis to
      obtain the oxygenation index. At the end of the experiment, the pulmonary wet/dry
      ratio (W/D), tumor necrosis factor-alpha (TNF-alpha), NO, malondialdehyde (MDA)
      and superoxide dismutase (SOD) contents in bronchoalveolar lavage fluid (BALF)
      were measured and the histological appearance of the lung tissue was observed.
      RESULTS: The oxygenation index was significantly higher (P<0.05), W/D ratio lower
      (P<0.05), and contents of TNF-alpha, NO and MAD in the BALF lower in the
      experimental group than in the control group (P<0.05). The activity of SOD
      increased significantly in the experimental group as compared with the control
      group (P<0.01), and the rabbits in the experimental group showed milder
      pathological changes. CONCLUSION: Intravenous pentoxifylline may improve
      pulmonary ventilation function and alleviate pulmonary injury, thus offering
      protection against pulmonary injury after one-lung ventilation.

PMID- 20034899
TI  - [Effects of urokinase on renal interstitial fibrosis and transforming growth
      factor-beta1 in the kidney of rats with chronic cyclosporine A nephropathy].
AB  - OBJECTIVE: To investigate the effects of urokinase on renal interstitial fibrosis
      and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with
      chronic cyclosporine A nephropathy. METHODS: Male Sprague-Dawley rats on low-salt
      diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000
      U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were
      given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy
      model. Masson staining was used to examine fibrin deposition. Western blotting
      and reversal transcription polymerase chain reaction were employed to evaluate
      urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene
      expressions, respectively. RESULTS: CsA can increase fibrin deposition and the
      expression of TGF-beta1 in the renal tissue, which were significantly reduced
      after uPA treatment (P<0.05). CONCLUSION: Continuous low-dose uPA treatment can
      reduce renal interstitial fibrosis in rats possibly in association with its
      inhibitory effect on TGF-beta1 expression.

PMID- 20034900
TI  - [Intravascular ultrasound-guided interventional therapy for borderline lesions in
      patients with acute coronary syndrome].
AB  - OBJECTIVE: To assess the efficacy and safety of intravascular ultrasound (IVUS)
      guided interventional therapy for borderline lesions in patients with acute
      coronary syndrome (ASC). METHODS: Thirty-one ASC patients with borderline lesions
      (coronary artery stenosis between 40%-70% confirmed by coronary arteriography
      [CAG]) and a minimal lumen area (MLA) of the infarction related artery(IRA) < or
      =4.0 mm(2) shown by IVUS underwent percutaneous coronary intervention (PCI).
      Another 31 PCI cases without IVUS were also enrolled as the control group. The
      minimal luminal diameter, cross section luminal area, total cross section, plaque
      area and area stenosis rate were measured before and after stent deployment at a
      conventional or higher pressure in the IVUS group. All the patients were followed
      up for 10-12 months and clinically evaluated 1, 3, 6 month and 12 months after
      the procedure to collect the data of angina recurrence, myocardial infarction and
      revascularization. RESULTS: All the 31 cases were successfully stented with
      satisfied CAG results (with residual stenosis <0, TIMI flow grade III) and
      without dissection or any related complications. Among the 32 stents, 28 showed
      insufficient adherence or underexpansion (stent malapposition) to require 18-20
      atm dilation or another high pressure balloon to attain the adequate IVUS
      results. CAG and IVUS were repeated in 22 patients (70.97%) of the IVUS group
      during the 10 to 12 months of follow up. No stent restenosis occurred with the in
      stent diameter late loss >50%, nor was in-stent thrombus found by IVUS.
      Endomembrane proliferation was found but without any significant difference.
      Minimal stent lumen area were not significantly different from the immediate
      results after PCI (10.12-/+1.15 mm(2) vs 8.98-/+2.12 mm(2), P>0.05). The 31
      patients in the control group were successfully stented with satisactory CAG
      results, but 3 suffered angina at 3-6 months who showed stent restenosis and
      insufficient stent adherence. CONCLUSION: IVUS can more effectively guide the
      interventional therapy for ACS borderline lesions and assess the immediate
      efficacy of therapy than CAG. Post-dilation with higher pressure (16-20 atm)
      guided by IVUS can further improve the procedural results. IVUS-guided PCI for
      ACS borderline lesions ensures high immediate and long-term success rate.

PMID- 20034902
TI  - [Application of 3D FIESTA sequence in magnetic resonance sialography for
      obstructive salivary diseases].
AB  - OBJECTIVE: To investigate the value of 3D FIESTA sequence in magnetic resonance
      sialography (MRS) in the diagnosis of obstructive salivary diseases. METHODS:
      Eleven patients with obstructive salivary diseases underwent MRS, and three
      dimensional (3D) reconstruction and virtual endoscopic images of the salivary
      gland ducts were obtained after MRS data post-processing for comparison with
      those of sialoendoscopy. RESULTS: The diagnostic accuracy of MRS was 72.7% for
      obstructive salivary diseases. The virtual endoscopy provided a visual field
      highly consistent with that by sialoendoscopy. CONCLUSION: MRS is capable of
      visualizing the tracts of salivary glands. MR virtual endoscopy can provide
      sufficient morphological and pathological data for preoperative assessment of
      salivary operations with sialoendoscopy.

PMID- 20034901
TI  - [Clinical significance of tumor interstitial T lymphocyte subset activity in non
      small-cell lung cancer].
AB  - OBJECTIVE: To study the relation of tumor interstitial T lymphocyte subset
      activity to the clinical staging of non-small-cell lung cancer (NSCLC) and the
      immune response. METHODS: Immunohistochemical staining for CD4(+), CD8(+) and
      CD4(+)CD25(+) Foxp3(+) (regulatory T cells, Treg) T cells was performed on
      paraffin-embedded tissues from 60 NSCLC cases. RESULTS: Compared to stage I/II
      NSCLC patients, patients in stage III/IV showed a significant decrease in the
      percentage of CD4(+) and CD4(+)/CD8(+) T cells (P<0.05) and an increase in CD8(+)
      and CD4(+)CD25(+) Foxp3(+) T cells (P<0.05). Treg cells were enriched in the
      tumor tissue as compared with those in the adjacent tissues. CONCLUSIONS: The
      proportion of CD4(+)CD25(+) Foxp3(+) Treg cells is positively correlated to the
      clinical staging of NSCLC, in which T cell-mediated immune response is
      suppressed.

PMID- 20034903
TI  - [Clinical and neuroimaging features of heroin spongiform leukoencephalopathy].
AB  - OBJECTIVE: To summarize the clinical and radiographic characteristics of heroin
      spongiform leukoencephalopathy (HSLE). METHODS: A clinical analysis of 42 cases
      of HSLE was conducted. RESULTS: Clinically, the patients with HSLE all had a
      positive history of inhalation of heated heroin vapor with acute or subacute
      onset in most cases, presenting initially cerebellar signs. Pyramidal tract
      lesion was frequently involved, but the sensory system usually remained normal.
      The consciousness disturbances may occur in the serious cases. Brain CT and
      magnetic resonance imaging (MRI) revealed extensive symmetric white matter
      lesions in the cerebrum and cerebellum, and in serious cases, the midbrain and
      pons could be damaged. Spongiform vacuoles degeneration of white matter
      characterized the predominant pathological changes. CONCLUSION: Spongiform
      leukoencephalopathy should be considered in a patient who shows acute cerebellar
      signs and reports a history of inhaling heated heroin vapor, and a definite
      diagnosis of HSLE can be made in such a case upon the identification of typical
      CT or MRI findings.

PMID- 20034904
TI  - [Regulatory effect of thalidomide on the expression of costimulatory molecules in
      patients with multiple myeloma].
AB  - OBJECTIVE: To investigate the expression of B7 co-stimulatory molecules in human
      multiple myeloma (MM) and the immunoregulatory effects of thalidomide on B7.1 co
      stimulator. METHODS: The immunoregulatory effects of thalidomide on the
      expression of B7-1 in human MM cell line was examined by detecting the changes in
      the expression of B7 co-stimulator on the cells using flow cytometry following
      the drug treatment. RESULTS: The expression of B7.1 co-stimulator was lowly
      expressed in human MM cell line and MM patients, with a positivity rate of 0.8
      and (2.19-/+2.13) for B7.1 and a rate of 26.4 and (30.28-/+28.11) for B7.2,
      respectively. Compared with the control group, the thalidomide-treated cells
      showed significantly increased percentage of CD-80 positive cells in a dose
      dependent manner (but not at 0.1 microg/ml) (P<0.01), with the highest percentage
      reaching (17.7-/+1.53)% at thalidomide concentration of 5 microg/ml. CONCLUSION:
      MM cells express low or undetectable levels of B7.1. Thalidomide can up-regulate
      the expression of B7-1 molecules on myeloma cells, which is probably one of the
      therapeutic mechanisms of thalidomide.

PMID- 20034905
TI  - [Establishment of mouse model of humoral immune response using rabbit red blood
      cells as the antigen].
AB  - OBJECTIVE: To establish a mouse model of humoral immune response by immunization
      with rabbit red blood cells (RRBCs). METHODS: The mice were immunized with RRBCs
      and the serum hemolysin level was measured by micro-hemolysis spectrophotometry.
      RESULTS: The peak time needed for hemolysin production against RRBCs was 6 days
      after the immunization, and 20% RRBCs in a total volume of 0.2 ml was optimal for
      intraperitoneal injection. Hydrocortisone (25 mg/kg) and cyclophosphamide (20
      mg/kg) inhibited hemolysin production. Mannatide (4 mg/kg) produced no
      significant effect on serum hemolysin level in normal mice, but significantly
      potentiated hemolysin production in immunosuppressed mice induced by
      cyclophosphamide (20 mg/kg). CONCLUSION: Intraperitoneal RRBC injection is
      feasible for establishing mouse models of humoral immune response.

PMID- 20034906
TI  - [Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin
      radioimmunoimaging].
AB  - OBJECTIVE: To study the mechanism of cardiotoxicity associated with Herceptin.
      METHODS: Herceptin was labeled with iodine-131 using the Iodogen method.
      Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I
      Herceptin injection to investigate the biodistribution of Herceptin. (131)I
      Herceptin uptake in each organ or tissue relative to that in the muscular tissue
      (O/M ratio) was calculated and compared. On the fifth day following the
      injection, the organs including the heart, lung, liver and muscles were taken for
      measurement of the weight and radiocounts. HER2 expression was measured by
      immunohistochemistry in these organs and tissues. RESULTS: The O/M ratio of the
      heart was significantly higher than that of the lung (P=0.032) and liver
      (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h
      (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher
      that that in the muscle and intestine, but lower than that in the lung and
      spleen. HER2 expression showed no significant difference between the myocardium
      and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).
      CONCLUSION: Myocardium expresses low levels of HER2 and accumulates Herceptin no
      more than the other tissues.

PMID- 20034907
TI  - [Protective effect of ischemic postconditioning on hepatic ischemia-reperfusion
      injury].
AB  - OBJECTIVE: To investigate the protective effect of ischemic postconditioning
      (IPC) against hepatic ischemia-reperfusion injury. METHODS: Twenty-four normal
      male Wistar rats were randomly divided into sham-operated group, ischemia
      reperfusion group (IR) and IPC group, and in the latter two groups, the rats were
      subjected to acute hepatic ischemia-reperfusion. IPC was achieved by several
      brief pre-reperfusion and withdrawn before persistent reperfusion. The
      concentration of malondialdehyde (MDA) and activity of several antioxidant
      enzymes in the hepatic tissue were measured. The cell apoptosis was detected by
      TdT-mediated dUTP-biotin nick end labeling (TUNEL) and the expression of Bcl-2
      protein measured by immunohistochemistry. The mitochondrial ultrastructural and
      morphological changes of the hepatic cells were observed by electron microscopy.
      RESULTS: Compared with IR group, IPC group showed significantly reduced
      concentration of MDA and the hepatocellular apoptotic index (P<0.05) with
      markedly enhanced activity of the antioxidant enzymes and Bcl-2 protein
      expression (P<0.05).The mitochondrial ultrastructural damage was also relieved
      obviously in IPC group. CONCLUSION: IPC can reduce the hepatocellular apoptosis
      after reperfusion and offers protection against hepatic IR injury.

PMID- 20034908
TI  - [Identification and genotyping of oncogenic type of human papillomavirus in
      paraffin-embedded cervical cancer samples in Guangzhou].
AB  - OBJECTIVE: To investigate human papillomavirus (HPV) infection and genotyping in
      patients with cervical cancer in Guangzhou in the last 3 decades. METHODS: HPV L1
      gene fragment in paraffin-embedded cervical cancer samples was amplified by HPV
      specific PCR with consensus primers, and typing of HPV strains was performed on
      the basis of sequence analysis of the PCR products. RESULTS: The positivity rates
      of HPV DNA was 26.2% in the 99 cases of cervical cancer. Five HPV genotypes were
      identified including HPV16, 18, 33, 52 and 58. CONCLUSION: HPV16, 58 and 33 are
      the most common genotypes of HPV, accounting for over 88.4% in the total infected
      cases, suggesting that the HPV genotypes closely related to cervical cancer is
      more centralized in Guangzhou.

PMID- 20034909
TI  - [A rapid colorimetric assay for viability of osteosarcoma cells after
      chemotherapy].
AB  - OBJECTIVE: To introduce a rapid colorimetric method for assessing the viability
      of osteosarcoma cells after chemotherapy. METHODS: Colorimetric assay and
      automatic microplate scanning spectrophotometer were used for assaying the
      viability of osteosarcoma cells. RESULTS: Close correlation was found between the
      absorbance at 570 nm of the formazan products and the number of viable
      osteosarcoma cells. CONCLUSION: An effective, sensitive and convenient
      colorimetric assay has been established to assess the survival of osteosarcoma
      cells following chemotherapy.

PMID- 20034910
TI  - [CT angiography-based simulation of the surgical approach in early operation for
      ruptured aneurysm].
AB  - OBJECTIVE: To simulate the surgical approaches for intracranial aneurysms using
      three-dimensional CT angiography (3D-CTA) and assess the value of 3D-CTA in early
      microneurosurgery for ruptured intracranial aneurysms. METHODS: Forty-eight
      patients with spontaneous subarachnoid hemorrhage due to ruptured intracranial
      aneurysm were confirmed by early operation. All the patients were classified
      according to Hunt-Hess, including 11 of grade I, 29 of grade II, and 8 of grade
      III. CTA was performed before the operation and surgical simulation was
      conducted. The preoperative findings on CTA and the intraoperative findings were
      compared and the clinical value of cerebral 3D-CTA was analyzed. RESULTS: Pre
      operative 3D-CTA clearly displayed the location, size and shape of the aneurysms,
      the axis direction of the aneurysm apex and the width of aneurysm neck. The
      spatial relation between the parent aneutysm artery, the aneurysm, the peripheral
      vessels and the bony structures were also demonstrated. These findings were
      basically consistent with the intraoperative findings. The Glasgow outcome score
      was 5 in 41 patients, 4 in 4 patients, 3 in 2 patients, and 2 in 1 patient upon
      discharge from the hospital. CONCLUSIONS: Preoperative 3D-CTA examination can
      simulate the surgery for ruptured aneurysms to help improve the surgical success
      rate.

PMID- 20034911
TI  - [Changes in liver function and immune function following laparoscopic and
      traditional open cholecystectomy: a comparative study].
AB  - OBJECTIVE: To compare the effect of laparoscopic cholecystectomy (LC) and open
      cholecystectomy (OC) on liver function and immune function. METHODS: Forty-two
      patients with normal liver function underwent LC (n=21) or OC (n=21) according to
      the patients' preference. One day before and 7 days after the operations, the
      liver functions (ALT, AST, TBIL, ALB) and immune functions (CD3, CD4, CD8, NK
      cell percentage, IgA, IgM, IgG and C3, C4) of the patients were measured.
      RESULTS: No statistical differences were found in the liver functions or immune
      functions between the two groups after the operation. CONCLUSION: LC and OC show
      no significant difference in the effects on the liver function and immune
      function.

PMID- 20034912
TI  - [Analgesic and anti-inflammatory effects of Hanshibi tablet in mice and its
      effect on synovial pathology in a rat model of rheumatoid arthritis].
AB  - OBJECTIVE: To evaluate the analgesic and anti-inflammatory effects of Hanshibi
      tablet in Kunming mice and the effect of the tablet in ameliorating synovial
      pathology in a rat model of rheumatoid arthritis (RA). METHODS: Stretching test,
      capillary permeability and ear swelling test of Kunming were performed to observe
      the analgesic and anti-inflammatory effects of Hanshibi tablet administered
      intragastrically at different doses. In a SD rat model of RA induced by heat
      inactivated Mycobacterium tuberculolytic H37Ra (Mtb), the effect of the tablet on
      the symptoms and progression of arthritis was observed regularly, and the numbers
      of the peripheral white blood cells, platelets and lymphocytes and mononuclear
      cells were measured. HE staining was used to examine the pathology of the rat
      ankle, and flow cytometry performed to monitor the changes in the T lymphocyte
      subsets. RESULTS: Hanshibi tablet treatment reduced the writhing response
      frequency and prolonged the stretching latency of Kunming mice. The tablet also
      inhibited the acetic acid-induced increase in capillary permeability and ear
      swelling. In the rat model of RA, administration of the tablet resulted in
      reduced ratio of CD4(+)/CD8(+), and significantly ameliorated synovial pathology.
      CONCLUSION: Hanshibi tablet has obvious analgesic and anti-inflammatory effects
      and ameliorates the synovial pathology in the rat model of RA possibly by
      regulating CD4(+)/CD8(+) balance.

PMID- 20034913
TI  - [Dynamic changes of plasma tissue factor and tissue factor pathway inhibitor-1
      and their clinical significance in patients with multiple traumas].
AB  - OBJECTIVE: To investigate the dynamic changes of plasma tissue factor (TF) and
      tissue factor pathway inhibitor-1 (TFPI-1) and their significance in patients
      with multiple traumas. METHODS: The plasma levels of TF, TFPI-1 and D-dimer were
      detected using enzyme-linked immunosorbent assay in patients on the first, second
      and third days after multiple traumas, with 25 healthy adults as the normal
      control. RESULTS: The levels of plasma TF and D-dimer increased on the first day,
      and reached the peak value on the second day, but TFPI-1 decreased with the
      passage of time. Significant differences were found in the levels of plasma TF
      between the multiple trauma patients (on the first, second, third posttrauma
      days) and the control group (P<0.01). Significant differences were also found in
      plasma TFPI-1 and D-dimer between the patients (on the second and third
      posttrauma days) and the control group (P<0.05). CONCLUSION: Coagulation
      dysfunction and secondary fibrinolysis occur in the early stage of multiple
      traumas. Dynamic detection of plasma TF, TFPI and D-dimer is beneficial for
      understanding the degree of diffuse intravascular coagulation and inflammation
      after the trauma and can be used as the reference indexes for clinical diagnosis
      and therapy.

PMID- 20034914
TI  - [Removal of metallic foreign body in the soft tissue under fluoroscopy: 10 years
      of experiences].
AB  - OBJECTIVE: To summarize our 10-year experience with percutaneous fluoroscopically
      guided removal (PFGR) of metallic foreign body (MFB) in the soft tissue. METHODS:
      PFGR was performed in 65 patients for removing a total of 368 MFBs from the soft
      tissues. The MFBs ranged from 0.2 to 0.3 cm in length embedded in the soft tissue
      for 7 days to 8 years. For superficial MFBs, the MFBs were removed directly with
      curved forceps under real time fluoroscopy. For deep MFBs, trocar technique was
      applied using the instruments for percutaneous diskectomy, with the outer cannula
      inserted toward the foreign body under real-time fluoroscopy followed by MFB
      removal by grasping forceps. RESULTS: A total of 346 MFBs were successfully
      removed without any serious complications (success rate 94.0%), including 154
      removed directly and 192 MFBs with trocal technique. The time of the procedures
      and radiation exposure for MFB removal was 30 s to 20 min and 1-6 min,
      respectively. CONCLUSION: PGFR of MFBs in the soft tissue under fluoroscope is
      safe and effective. Direct removal using curved forceps is suitable for MFBs in
      superficial soft tissues, while trocal techniques needs to be utilized for deep
      MFBs.

PMID- 20034915
TI  - [Analysis of the risk factors of pulmonary fungal infections related to
      hematologic malignancies].
AB  - OBJECTIVE: To investigate the risk factors of pulmonary fungal infections related
      to hematologic malignancies. METHODS: A retrospective case-controlled study was
      conducted to analyze the patients with pulmonary fungal and bacterial infections
      in association with hematologic malignancies. The risk factors of pulmonary
      fungal infections related to hematologic malignancies were identified. RESULTS:
      Three hundred and four cases (194 of pulmonary fungal infections and 110 of
      pulmonary bacterial infections) were enrolled in this study. Univariate analysis
      and multivariate logistic regression show that such factors as corticosteroid,
      halo sign, previous fungal infections, ANC lower than 0.5 x 10(9)/L for over 10
      days, nodus near pleura, transplantation (immunodepressant use), chemotherapy,
      and broad spectrum antibiotics were all the independent risk factors of pulmonary
      fungal infections related to hematologic malignancies. CONCLUSION: There are many
      risk factors for pulmonary fungal infections related to hematologic malignancies,
      and early identification of these factors for timely antifungal treatment is of
      much clinical significance.

PMID- 20034916
TI  - [Application of neoadjuvant chemotherapy for operable breast cancer].
AB  - OBJECTIVE: To investigate the clinical value of neoadjuvant chemotherapy in the
      treatment of operable breast cancer. METHODS: A total of 120 patients with
      pathologically proven operable breast cancer were randomized into two groups to
      receive 2-4 cycles of neoadjuvant chemotherapy with docetaxel combined with
      pirarubicin (TThp) or docetaxel combined with epirubicin (TE). Operations were
      performed two weeks after the neoadjuvant chemotherapy. The short-term
      therapeutic effect, toxic reaction and the impact of neoadjuvant chemotherapy on
      the choice of surgical approaches were evaluated. RESULTS: The total effective
      rate for the primary sites was 87.2% in these patients, and the rate of breast
      conservation significantly increased from 12.7% to 41.8% (P<0.05), with a tumor
      resection rate of 97.2%. The major adverse effects of the therapy included
      leukopenia, nausea, vomiting and alopecia. CONCLUSION: Neoadjuvant chemotherapy
      can enhance the breast conservation rate, lower the clinical staging of the
      tumors and minimize the surgery area to improve the postoperative quality of life
      of the patients.

PMID- 20034917
TI  - [Dynamic changes of serum MCP-1 and MIP-2 chemokines after renal transplantation
      in rats].
AB  - OBJECTIVE: To investigate the changes in serum levels of chemokine MCP-1 and MIP
      2 after renal transplantation in rats and the influence of Cyclosporin A (CsA) on
      their levels. METHODS: Three groups of rats, namely untreated group, CsA group
      and isograft group underwent the renal transplantation, and the serum MCP-1 and
      MIP-2 levels of the recipients were tested using enzyme-linked immunosorbent
      assay (ELISA). RESULTS: The serum MCP-1 level peaked 6 hours after the operation
      and also in critical stages of acute rejection. The first peak of MCP-1 was
      postponed by the application of CsA, which did not affect the peak level
      (P>0.05). The second peak of MCP-1 did not occur in CsA-treated group. MIP-2
      concentration also peaked at 6 h after the operation in all the groups. The
      second peak of MIP-2, which was lower than the first one (P<0.05), occurred 9
      days after the transplantation. CONCLUSION: MCP-1 and MIP-2 in involved not only
      in the ischemia-reperfusion injury but also in severe acute rejection. CsA has no
      significant effect on serum levels of MCP-1 and MIP-2 following renal
      transplantation in rats.

PMID- 20034918
TI  - [Expression and mutations of PIK3CA gene in hepatocellular carcinomas].
AB  - OBJECTIVE: To investigate the expression and mutation of PIK3CA gene in
      hepatocellular carcinomas (HCC). METHODS: HCC samples and the corresponding
      adjacent tissues were collected from the surgical patients with pathologically
      verified diagnosis. The exons 1, 9 and 20 of PIK3CA gene were detected by PCR
      SSCP and DNA sequencing. Immnohistochemistry was employed to test the expression
      of PIK3CA gene in these samples. RESULTS: No mutation was found in exons 1, 9 or
      20 of PIK3CA gene in the HCC tissue and the adjacent tissues by PCR-SSCP and DNA
      sequencing, while abnormal superimposed peaks were found on the sequence map of
      exon 9 in 25 cases of HCC tissue. Immunohistochemistry showed that expression of
      PIK3CA was higher in the HCC tissue than in the corresponding adjacent tissue
      (50.81% vs 14.75%). CONCLUSION: PIK3CA gene mutation may exist in HCC in Guangxi,
      which can be associated with the development of HCC, but the ratio of hotspot
      mutations is low.

PMID- 20034919
TI  - Meaning and perspective in published research.

PMID- 20034921
TI  - Application of immunoassay for detection of Helicobacter pylori antigens in the
      dental plaque.
AB  - PURPOSE: The aim of this study was to determine the viability of the commercial
      test currently used for detection of H. pylori antigens in the stool for
      detection of H. pylori antigens in dental plaque. MATERIALS AND METHODS: A total
      of 164 dyspeptic patients entered the study; 95 H. pylori infected (positive
      result of at least 4 of 5 diagnostic tests: Campylobacter-like organisms test
      (CLO test), histology, culture, stool antigens, serology) and 69 noninfected
      (negative results of 4 diagnostic tests: CLO test, histology, culture, stool
      antigens). Dental plaque was collected from natural teeth of the patients and
      incubated in microaerophilic conditions for 72 hours before immunoassay. RESULTS:
      Experimental findings included that optimal dental plaque weight to perform the
      examination was over 2 mg and that preliminary incubation increased significantly
      the number of positive results (p<0.002). It was also found that H. pylori
      antigens in the dental plaque were positive in 81.2% of infected and only 17.7%
      of non-infected subjects (p<0.001), while the reproducibility of results was 95%.
      CONCLUSIONS: The immunoassay for detection of H. pylori antigens in the stool may
      be used, after minor adaptations (specifically pre-incubation in microaerophilic
      conditions) for H. pylori antigen detection in dental plaque.

PMID- 20034922
TI  - The EGFR expression in gastric mucosa of children infected with Helicobacter
      pylori.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) modulates balance between
      proliferation and apoptosis in gastric mucosa of the gastrointestinal tract. The
      aim of the study was to evaluate immunohistochemically the EGFR expression in
      epithelial and gland cells of antral mucosa in children infected with
      Helicobacter pylori (H. pylori). MATERIAL/METHODS: The study included 44
      children, aged from 5 to 18 years (mean age 13+/-3.4 years) with dyspeptic
      symptoms, of whom 30 (68.2%) children were infected with H. pylori, 14 (31.8%)
      children constituted controls. Endoscopic and histopathological assessment of
      antral mucosa samples was performed according to the Sydney System. Samples taken
      from gastroscopy were prepared to evaluate EGFR expression in epithelial and
      gland cells of antrum mucosa according to the manual of a detection kit of
      EnVision+System-HRP (DAKO). RESULTS: In children H. pylori infected, the EGFR
      expression in epithelial cells of antral mucosa equaled on average 82.5+/-15
      cells/mm2 and ranged from 45.0 to 98.0 cells/mm2 as well as differed
      statistically significantly when compared to controls (10.2+/-5.0 cells/mm2)
      (p<0.001). In children with H. pylori infection, the EGFR expression in gland
      cells of antral mucosa ranged from 2.0 to 85.0 cells/mm2 (mean 25.7+/-22.6
      cells/mm2); was lower and differed statistically significantly from controls
      (54.2 +/- 29.6 cells/mm2) (p<0.001). In children H. pylori infected, there was a
      statistically significant difference (p<0.001) between the EGFR expression in
      epithelial and in gland cells of antral mucosa. CONCLUSION: The increased EGFR
      expression in epithelial cells in comparison with gland cells of antral mucosa in
      children with H. pylori infection may suggest its role in regeneration processes
      of gastric mucosa.

PMID- 20034923
TI  - Transcriptional activity of genes-encoding kinin B1 and B2 receptors and kinin
      dependent genes in nasal polyps.
AB  - PURPOSE: The pro-inflammatory effects of kinins are mediated by two bradykinin
      receptors: BR1 and BR2. The aim of this study was to evaluate the expression
      profile of kinin receptor genes by an estimation of mRNA levels in human nasal
      polyps (NP) and normal mucosa (NM). MATERIAL AND METHODS: BR1 and BR2-dependent
      genes differentially transcribed in NP were investigated using oligonucleotide
      microarray technology. The mRNA copy number of BR1, BR2 and TIMP1 genes was
      assessed by QRT-PCR. Thirty six eosinophilic (ENP), 17 neutrophilic nasal polyps
      (NNP) and 28 NM samples were included into the study. RESULTS: Among 92 genes
      encoding proteins involved in signal transduction via B1 and B2 kinin receptors
      TIMP1 was found to be 2,63-fold higher in the NP than in NM. Increased TIMP1 gene
      expression was proved by QRT-PCR (p=0,003). Moreover two genes: FOS and PTGS1
      presented higher (3,82- and 4,27-fold, respectively) expression in NM compared to
      NP tissues. In QRT-PCR analysis insignificantly higher expression of gene
      encoding BR1 in ENP [2564 mRNA copies/microg RNA (22-32863)] compared with NM
      [1426 copies mRNA (15-27995)] was found. mRNA expression for the BR2 in ENP [9872
      copies mRNA (19-244832)] was insignificantly higher than in NM [5753 copies (46
      199658)]. BR2 mRNA was the predominant transcript in most NP and NM samples
      followed by BR1 mRNA (p<0,01). There was a positive correlation between the
      expression of BR1 and BR2 in the ENP (r=0,91; p<0,01) and NNP (r=0,6; p<0,01).
      CONCLUSIONS: We did not document any changes in the expression profile of kinin
      receptors in the analyzed groups, which may suggest that kinin receptors do not
      make an important contribution in the etiology of NP.

PMID- 20034929
TI  - Case-control study of risk factors for sporadic Campylobacter infections in
      northeastern Spain.
AB  - BACKGROUND: An age-matched case-control study was conducted in northeastern Spain
      to identify major risk factors for sporadic Campylobacter infections and their
      relative importance. METHODS: Cases were aged >6 months, residents of Sector
      Sanitario Huesca with diarrhea and confirmed culture of Campylobacter not related
      to outbreak. For each case <15 years of age, the patient closest in age to the
      case was selected from the medical records of the case's pediatrician to serve as
      a control. If the case was >or=15 years of age, the control was nominated by the
      case. RESULTS: Eighty one cases (median age 2.3 years, 79% <15 years) and 81
      controls were enrolled. Three exposures, in the 7 days prior to symptom onset,
      were independent predictors for illness after multivariate conditional logistic
      regression analysis: consuming three or more times chicken [odds ratio
      (OR)(adjusted) = 6.1; confidence interval (CI): 2.0-18.5; population attributable
      fraction (PAF) = 36.1%], consuming sliced deli meat unhygienically handled at
      retail stores (OR(adjusted) = 4.1; CI: 1.2-13.2; PAF = 24.5%) and contact with
      animals (OR(adjusted) = 2.8; CI: 1.1-7.3; PAF = 19. 0%). Among cases <15 years of
      age, only consuming chicken >or=3 times (OR(adjusted) = 7.8; CI: 2.2-26.7; PAF =
      43.6%) and contact with animals (OR(adjusted) = 3.7; CI: 1.2-11.0; PAF = 25.1%)
      were independent predictors for disease. Consuming sliced deli meat
      unhygienically handled at retail stores was significantly more frequent among <15
      year age group (56.3% versus 26.6.0%, P = 0.04). CONCLUSION: A control programme
      for Campylobacter in the food chain and targeted food-safety education to prevent
      cross-contamination seem warranted to decrease the opportunity of human exposure
      to the pathogen in northeastern Spain.

PMID- 20034928
TI  - Default network connectivity reflects the level of consciousness in non
      communicative brain-damaged patients.
AB  - The 'default network' is defined as a set of areas, encompassing posterior
      cingulate/precuneus, anterior cingulate/mesiofrontal cortex and temporo-parietal
      junctions, that show more activity at rest than during attention-demanding tasks.
      Recent studies have shown that it is possible to reliably identify this network
      in the absence of any task, by resting state functional magnetic resonance
      imaging connectivity analyses in healthy volunteers. However, the functional
      significance of these spontaneous brain activity fluctuations remains unclear.
      The aim of this study was to test if the integrity of this resting-state
      connectivity pattern in the default network would differ in different
      pathological alterations of consciousness. Fourteen non-communicative brain
      damaged patients and 14 healthy controls participated in the study. Connectivity
      was investigated using probabilistic independent component analysis, and an
      automated template-matching component selection approach. Connectivity in all
      default network areas was found to be negatively correlated with the degree of
      clinical consciousness impairment, ranging from healthy controls and locked-in
      syndrome to minimally conscious, vegetative then coma patients. Furthermore,
      precuneus connectivity was found to be significantly stronger in minimally
      conscious patients as compared with unconscious patients. Locked-in syndrome
      patient's default network connectivity was not significantly different from
      controls. Our results show that default network connectivity is decreased in
      severely brain-damaged patients, in proportion to their degree of consciousness
      impairment. Future prospective studies in a larger patient population are needed
      in order to evaluate the prognostic value of the presented methodology.

PMID- 20034930
TI  - Socio-economic differences in self-esteem of adolescents influenced by
      personality, mental health and social support.
AB  - BACKGROUND: Previous studies indicate that self-esteem is lower among adolescents
      of low socio-economic status and is associated with a number of intrapersonal,
      interpersonal and socio-cultural factors. Evidence on the mechanisms by which
      these factors contribute to the connection between socio-economic status and
      developing self-esteem is incomplete, however. The purpose of this cross
      sectional study is to assess whether personality, mental health and social
      support contribute to the relationship between socio-economic status and self
      esteem. METHODS: A sample of 3694 elementary-school students from Slovakia (mean
      age = 14.3 years, 49% boys) filled out the Rosenberg Self-esteem Scale, the
      Family Affluence Scale, the Ten-Item Personality Inventory, the 12-item General
      Health Questionnaire and the Perceived Social Support Scale. RESULTS:
      Hierarchical linear regression showed family affluence, personality dimensions of
      extroversion, emotional stability and openness to experience, as well as mental
      health subscales and social support from family and significant others to be
      associated with self-esteem. Results indicate that personality dimensions and
      mental health subscales contribute to the association between family affluence
      and self-esteem. CONCLUSION: The contribution of personality and mental problems
      in the relation between socio-economic status and self-esteem may have important
      implications for the design of promotional programs aimed at enhancing self
      esteem.

PMID- 20034931
TI  - Smoking in prison: a hierarchical approach at the crossroad of personality and
      childhood events.
AB  - BACKGROUND: Smoking has long been considered part of prison culture and studies
      have shown a high prevalence of smoking within correctional facilities. METHODS:
      A self-administered, anonymous questionnaire was administered to 173 male
      prisoners in the Chalkida prison, Greece. To assess current smoking habits, a
      hierarchical approach was adopted. The underlying conceptual framework included:
      (i) demographic parameters, (ii) adverse childhood history (physical abuse,
      parental neglect, parental divorce, alcoholism in the family, sexual abuse and
      psychiatric condition in the family), (iii) education, personality traits, such
      as impulsivity (Barrat Impulsivity Scale-11), aggression (Buss-Perry Aggression
      Questionnaire and Lifetime History of Aggression), and personal history of mental
      disease, (iv) prison-related features (duration of sentence, sentence already
      served and change in smoking habits during imprisonment). RESULTS: Eighty
      percentage of the study sample reported current smoking; 43.4% disclosed
      deterioration in their smoking habits during imprisonment. The hierarchical
      approach pointed to: (i) adverse childhood events, i.e. alcoholism in the family
      [adjusted odds ratio (OR) = 6.29, 95% confidence interval (CI): 2.44-16.25],
      psychiatric condition in the family (adjusted OR = 4.10, 95% CI: 1.31-12.84),
      physical abuse (adjusted OR = 2.90, 95% CI: 1.30-6.46), parental neglect
      (adjusted OR = 2.66, 95% CI: 1.19-5.95), parental divorce (adjusted OR = 2.14,
      95% CI: 1.00-4.56), and (ii) impulsivity (adjusted OR = 2.26, 95% CI: 1.12-4.58)
      as independent risk factors. In addition, deterioration of smoking habits during
      imprisonment exerted an effect of borderline significance (adjusted OR = 2.02,
      95% CI: 0.97-4.24). CONCLUSIONS: Heavy smoking in prison principally integrates
      two components: unfavourable childhood and current personality traits
      (impulsivity).

PMID- 20034932
TI  - Health research in the European Union: over-controlled but under-measured?

PMID- 20034933
TI  - A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver
      disease disrupts triglyceride hydrolysis.
AB  - Obesity and insulin resistance are associated with deposition of triglycerides in
      tissues other than adipose tissue. Previously, we showed that a missense mutation
      (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is
      associated with increased hepatic triglyceride content in humans. Here we
      examined the effect of the I148M substitution on the enzymatic activity and
      cellular location of PNPLA3. Structural modeling predicted that the substitution
      of methionine for isoleucine at residue 148 would restrict access of substrate to
      the catalytic serine at residue 47. In vitro assays using recombinant PNPLA3
      partially purified from Sf9 cells confirmed that the wild type enzyme hydrolyzes
      emulsified triglyceride and that the I148M substitution abolishes this activity.
      Expression of PNPLA3-I148M, but not wild type PNPLA3, in cultured hepatocytes or
      in the livers of mice increased cellular triglyceride content. Cell fractionation
      studies revealed that approximately 90% of wild type PNPLA3 partitioned between
      membranes and lipid droplets; substitution of isoleucine for methionine at
      position 148 did not alter the subcellular distribution of the protein. These
      data are consistent with PNPLA3-I148M promoting triglyceride accumulation by
      limiting triglyceride hydrolysis.

PMID- 20034934
TI  - A comprehensive proteomic analysis of the type III secretome of Citrobacter
      rodentium.
AB  - Enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter
      rodentium belong to the family of attaching and effacing (A/E) bacterial
      pathogens. They intimately attach to host intestinal epithelial cells, trigger
      the effacement of intestinal microvilli, and cause diarrheal disease. Central to
      their pathogenesis is a type III secretion system (T3SS) encoded by a
      pathogenicity island called the locus of enterocyte effacement (LEE). The T3SS is
      used to inject both LEE- and non-LEE-encoded effector proteins into the host
      cell, where these effectors modulate host signaling pathways and immune
      responses. Identifying the effectors and elucidating their functions are central
      to understanding the molecular pathogenesis of these pathogens. Here we analyzed
      the type III secretome of C. rodentium using the highly sensitive and
      quantitative SILAC (stable isotope labeling with amino acids in cell culture)
      based mass spectrometry. This approach not only confirmed nearly all known
      secreted proteins and effectors previously identified by conventional biochemical
      and proteomic techniques, but also identified several new secreted proteins. The
      T3SS-dependent secretion of these new proteins was validated, and five of them
      were translocated into cultured cells, representing new or additional effectors.
      Deletion mutants for genes encoding these effectors were generated in C.
      rodentium and tested in a murine infection model. This study comprehensively
      characterizes the type III secretome of C. rodentium, expands the repertoire of
      type III secreted proteins and effectors for the A/E pathogens, and demonstrates
      the simplicity and sensitivity of using SILAC-based quantitative proteomics as a
      tool for identifying substrates for protein secretion systems.

PMID- 20034935
TI  - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a SUMO E3 ligase that is
      SIM-dependent and SUMO-2/3-specific.
AB  - Sumoylation has emerged as a major post-translational modification of cellular
      proteins, affecting a variety of cellular processes. Viruses have exploited the
      sumoylation pathway to advance their own replication by evolving several ways to
      perturb the host sumoylation apparatus. However, there has been no report of
      virally encoded enzymes directly involved in catalyzing the sumoylation reaction.
      Here, we report that the K-bZIP protein encoded by Kaposi's sarcoma-associated
      herpesvirus (KSHV) is a SUMO E3 ligase with specificity toward SUMO2/3. K-bZIP is
      a nuclear factor that functions to modulate viral gene expression and to prolong
      the G1 phase, allowing viral transcription and translation to proceed at the
      early stage of infection. In addition to functioning as a transcriptional factor,
      we show that K-bZIP carries a SIM (SUMO-interacting motif), which specifically
      binds to SUMO-2/3 but not SUMO-1. K-bZIP catalyzes its own SUMO modification as
      well as that of its interacting partners such as the cellular tumor suppressor
      proteins p53 and Rb, both in vitro and in vivo. This reaction depends on an
      intact SIM. Sumoylation of p53 leads to its activation and K-bZIP is recruited to
      several p53 target chromatin sites in a SIM-dependent manner. In addition to the
      identification of a viral SUMO-2/3 E3 ligase, our results provide additional
      insights into the mechanisms whereby K-bZIP induces cell cycle arrest.

PMID- 20034936
TI  - Abdominal aortic aneurysm repair in obese patients: improved outcome after
      endovascular treatment compared with open surgery.
AB  - PURPOSE: To investigate outcomes in obese patients with abdominal aortic aneurysm
      (AAA) treated with elective open or endovascular repair (EVAR). STUDY DESIGN: We
      compared the outcomes of obese patients with AAA treated with elective open
      repair and EVAR. Obesity was defined as a body mass index (BMI) > or =30 kg/m(
      2). RESULTS: A total of 56 patients with a BMI > or =30 kg/m(2) were identified
      for analysis (mean age 70 +/- 8 years; mean BMI 34 +/- 4 kg/m(2), and 95% [n =
      53] were male). Open surgery was performed in 55% (n = 31). The in-hospital
      complication rate (including nonsurvivors) was significantly increased after open
      repair compared with EVAR (26% vs 4%, P = .033). Mortality did not differ
      significantly during 3 years of follow-up (P = .816). Length of stay, intensive
      care unit (ICU) stay, and need for ventilation were significantly increased after
      open surgery compared with EVAR. CONCLUSIONS: We observed improved short-term
      outcomes among obese AAA patients after EVAR compared to open repair.
      Endovascular repair may be preferable in obese patients with AAA.

PMID- 20034937
TI  - Atorvastatin modulates matrix metalloproteinase expression, activity, and
      signaling in abdominal aortic aneurysms.
AB  - Statins may reduce abdominal aortic aneurysm (AAA) progression. We sought to
      measure how atorvastatin (AT) treatment might modulate matrix metalloproteinase
      (MMP) expression and/or activity in human AAA. Tissue from human AAAs at surgical
      repair was obtained from patients who were either not on statins (NST, n = 19) or
      treated with AT (n = 19). Immunoblots measured expression and zymography measured
      activity. Expression of most proteins was greater in the central compared with
      distal AAA region. Matrix metalloproteinase 1, MMP2, MMP3, MMP9, Tissue Inhibitor
      of Metalloproteinase (TIMP2), TIMP3, TIMP4, or total Sma Mothers Against
      Decapentaplegia (SMAD2) expression did not differ with treatment. There was a
      trend toward reduced MMP8 and TIMP1 expression and MMP2 zymographic activity in
      the AT-treatment group. In contrast, AT-treated samples had significantly reduced
      MMP13 (P = .02), latent-transforming growth factor (TGF)-beta (P = .02), and
      phospho-SMAD2 (P = .029) expression than NST-treated samples. We conclude that
      the AT-mediated decrease in MMP expression and activity reduces TGF-beta
      signaling in the central region of human AAAs.

PMID- 20034938
TI  - Management of a catecholamine-secreting paraganglioma requiring aortic
      reconstruction.
AB  - INTRODUCTION: Retroperitoneal paragangliomas are rare extraadrenal
      pheochromocytomas that can involve major vascular structures. RESULTS AND
      DISCUSSION: A case of periaortic catecholamine-secreting paraganglioma was
      reviewed and literature search performed to summarize the current surgical
      management of this disease process. CONCLUSION: Resection for cure of
      retroperitoneal paragangliomas with vascular reconstruction can be performed with
      acceptable morbidity and mortality with the use of current vascular techniques.

PMID- 20034939
TI  - Endovascular repair of 2 iliac pseudoaneurysms and arteriovenous fistula
      following spine surgery.
AB  - PURPOSE: To describe endovascular repair of traumatic iliac pseudoaneurysm and
      arteriovenous fistula (AVF) following spinal surgery. CASE REPORT: A 48-year-old
      male underwent minimally invasive L5-S1 hemilaminectomy, foraminotomy, and
      microdiscectomy spinal surgery for trauma related to a motor-vehicle accident.
      Postoperative angiogram demonstrated pseudoaneurysm of the right internal iliac
      artery and AVF at the common iliac bifurcation with the right iliac vein with
      prompt filling of the iliac vein and vena cava. The second patient, a 25-year-old
      female, underwent minimally invasive L4-S1 hemilaminectomy, foraminotomy, and
      microdiscectomy spinal surgery for intractable pain and was complicated with
      postoperative symptoms of congestive heart failure. Postoperative angiogram
      demonstrated AVF between the right common iliac artery and vein with associated
      pseudoaneurysm formation. Endovascular repair was performed in both cases. Follow
      up imaging revealed no endoleak and complete pseudoaneurysm and AVF exclusion.
      CONCLUSIONS: Endovascular repair of iliac injuries following spine surgery can be
      successfully performed with minimal morbidity.

PMID- 20034940
TI  - Hybrid procedures for complex thoracoabdominal aortic aneurysms: early results
      and secondary interventions.
AB  - BACKGROUND: Hybrid procedures for thoracoabdominal aortic aneurysms (TAAA) have
      been previously described as an attractive alternative to open reconstruction.
      PATIENTS AND METHODS: Between 1999 and 2009, 16 patients with a median age of
      67years underwent hybrid repair of a TAAA (Crawford type I: 3, type II: 3, type
      III: 1, and type IV: 9). In 94%, 3 and more severe comorbidities were present,
      with previous aortic surgery in 56% of the patients; elective/urgent repair was
      done in 10 and emergent surgery in 6 patients. RESULTS: Primary technical success
      was 100%, with 31 vessels grafted. Elective/urgent mortality was 20% (2 of 10)
      and emergent mortality 50% (3 of 6). During follow-up time (median: 12 months) 2
      patients died and 2 patients had to undergo secondary interventions. CONCLUSION:
      In high-risk patients especially after prior aortic surgery hybrid repair of TAAA
      is feasible. However, due to high mortality rates especially in the emergent
      situation this procedure should be reserved only for decidedly selected patients.

PMID- 20034941
TI  - Continuous intraarterial thrombolysis for early hepatic artery thrombosis
      following liver transplantation: case report.
AB  - Hepatic artery thrombosis remains one of the major causes of graft failure and
      mortality in liver transplant recipients. Urgent re-transplantation has been
      considered as mainstay therapy; however, even with re-transplantation mortality
      of more than 50% has been reported by many series. Early detection on Doppler
      ultrasonography and subsequent revascularization in asymptomatic patients can
      avoid graft loss. Endovascular therapy including intra-arterial thrombolysis,
      percutaneous transluminal angioplasty, and stent placement have shown encouraging
      results in recent years; nevertheless, their use remains controversial due to
      potential risk of bleeding. We present a case of early hepatic artery thrombosis
      following liver transplantation treated successfully with continuous
      transcatheter intra-arterial thrombolysis using tissue plasminogen activator (t
      PA).

PMID- 20034942
TI  - The role of anatomic factors in predicting success of endovascular repair of
      thoracic aortic aneurysms.
AB  - OBJECTIVE: We evaluated the results of thoracic endovascular aneurysm repair
      (TEVAR) to determine what anatomic factors influenced the clinical outcomes.
      METHODS: Preoperative computed tomography (CT) angiograms of 65 patients who
      underwent TEVAR were analyzed using 3-dimensional imaging. The proximal and
      distal neck, thoracic aneurysm, and iliac arteries were measured for angulation,
      diameter, length, calcification, and tortuosity. Immediate technical success and
      clinical success were measured. RESULTS: Immediate technical success was achieved
      in 91% (59 of 65) of the patients analyzed. One patient died in the operating
      room during treatment of rupture. Clinical success was achieved in 83% (54 of 65)
      of patients at follow-up. Four patients had small endoleaks with no sac
      enlargement at follow-up. One patient was converted to open repair. Severe iliac
      calcification was found to be significant for deployment failure. The mean follow
      up is 8 months (1-36 months). CONCLUSION: Increased iliac calcification and
      increased iliac tortuosity correlate with an inability to successfully deploy the
      device.

PMID- 20034943
TI  - Current management of mesenteric extrahepatic arterioportal fistulas: report of a
      case treated with a gastroduodenal artery stent graft and literature review.
AB  - Spontaneous arteriovenous fistulation of a pseudoaneurysm into superior
      mesenteric vein (SMV) has rarely been reported. We present the case of a 61-year
      old woman who presented with a post pancreatic arterioportal fistula (APF) that
      was successfully managed by stent graft (SG) placement in the gastroduodenal
      artery (GDA). We also review the published experience of the endovascular
      management of mesenteric extrahepatic APFs. This review demonstrates the
      evolution from open surgical to endovascular management for majority of these
      patients.

PMID- 20034944
TI  - Traumatic fracture of polytetrafluoroethylene axillofemoral bypass graft.
AB  - We report traumatic disruption of a ringed polytetrafluorethylene (PTFE)
      axillofemoral bypass (AFB) graft due to a fall. We also review the literature of
      previously reported blunt traumatic PTFE graft disruptions. A 75-year-old man
      with previous bilateral AFB grafting presented with a painful left chest wall
      mass after a fall from standing height. Chest computed tomography (CT) revealed a
      large chest wall hematoma. The patient underwent evacuation of the hematoma,
      resection of the fractured graft, and placement of an interposition PTFE graft.
      Two prior case reports have documented the midportion PTFE graft disruption from
      blunt trauma. Our case report demonstrates the potential for disruption of the
      midportion of ringed PTFE AFB grafts with direct blunt trauma. The diagnosis was
      confirmed by CT scan and the graft was successfully repaired with an
      interposition graft.

PMID- 20034945
TI  - Midterm results from internal iliac artery branched endovascular stent grafts.
AB  - PURPOSE: To evaluate the midterm feasibility, efficacy and safety of internal
      iliac artery branch grafts for endovascular repair of aortoiliac, common iliac,
      and internal iliac artery aneurysms. METHODS: Between December 2006 and September
      2008, 8 patients underwent elective endovascular repair of aortoiliac, common
      iliac, and internal iliac artery aneurysms. Computed tomography aortography (CTA)
      was used to detect postoperative endoleak, stent migration, branch patency, and
      aneurysm sac expansion. RESULTS: All stent grafts were correctly implanted.
      However, intraoperative branch occlusion occurred in 2 of 8 cases. Both
      occlusions have been managed conservatively, with only 1 patient suffering
      detrimental symptoms. One endoleak was found. Median follow up by CT was 402 days
      (range 77 to 718 days). No patients died. CONCLUSIONS: Midterm results are
      encouraging for endovascular branch grafts to include the internal iliac artery.
      However, patient selection is of great importance and our series illustrates the
      value of caution and multidisciplinary teamwork.

PMID- 20034946
TI  - Through with the flu: how free family and caregiver immunization protects sick
      neonates.
AB  - Newborns represent the pediatric population most at risk for influenza-related
      morbidity and mortality, especially premature newborns and those with chronic
      disease. Compounding this problem is the fact that influenza immunizations are
      ineffective until 6 months of age. This article describes a successful program
      that follows the "cocoon" theory of immunization. Free influenza vaccines were
      given in the nursery to all family members, caregivers, and others living in the
      homes of discharged infants. Planning and implementation steps are described,
      along with lessons learned during implementation. The response to the program
      exceeded expectations, with 185 contacts immunized. Future plans include the
      expansion of the current program to include the H1N1 influenza vaccine and the
      Tdap vaccine. The described vaccination effort encourages and substantiates the
      benefits of cocoon immunization in other nurseries across the nation.

PMID- 20034947
TI  - Triple dye plus rubbing alcohol versus triple dye alone for umbilical cord care.
AB  - Current practices for umbilical cord care vary across centers, but the evidence
      regarding these practices and their impact on cord separation, complications, and
      health care use are limited. The objective of this study was to compare the
      effect of triple dye alone (brilliant green, crystal violet, and proflavine
      hemisulfate) versus triple dye plus rubbing alcohol (isopropyl alcohol) twice
      daily on time to umbilical cord separation, complications, and health care use.
      For the 90 newborns who completed the study, there were no significant
      differences between treatment groups for time to cord separation, cord-related
      morbidities, or cord-related urgent care. Based on these study results, there
      does not appear to be significant benefit to the addition of twice daily
      applications of rubbing alcohol to neonatal umbilical cords following triple dye
      treatment after birth.

PMID- 20034948
TI  - Leg pain in an infant.
AB  - Nonaccidental trauma can be difficult to differentiate from osteogenesis
      imperfecta (OI), especially in the face of multiple fractures. When nonaccidental
      trauma is being considered, medical causes of injury must be ruled out. In this
      report, we discuss the case of an 11-month-old female infant who presented with a
      transverse femur fracture and was also found to have a healing transverse humeral
      fracture and rib fractures. Medical causes of the fractures were investigated by
      performing an analysis of urine organic acids, serum amino acids, vitamin D,
      parathyroid hormone, ceruloplasmin, copper, and blood sequencing for COL1A1 and
      COL1A2. A mutation of the gene COL1A1 was found, which is consistent with OI type
      I.

PMID- 20034949
TI  - Rosiglitazone ameliorates endotoxin-induced organ damage in conscious rats.
AB  - Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)-gamma
      agonist. By inhibiting nuclear factor kappaB (NF-kappaB), it decreases tumor
      necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) and has an anti
      inflammatory effect. Endotoxin shock can induce the production of several
      inflammatory mediators such as TNF-alpha and IL-6, leading to multiple organ
      dysfunction and death. We investigated the effects of rosiglitazone (.3 mg/kg,
      intravenous administration) on the physiologic attributes and cytokine levels in
      endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous
      injection of Klebsiella pneumoniae lipopolysaccharides (LPSs; 10 mg/kg) in
      conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were
      continuously monitored for 24 hr after LPS administration. Levels of biochemical
      and cytokine parameters, including glutamic oxaloacetic transaminase (GOT),
      glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre),
      lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, TNF-alpha, and
      IL-6 were measured at 0, 1, 3, 6, 12, and 24 hr after sepsis. Endotoxin shock
      significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, glucose, TNF-alpha,
      and IL-6 levels and HR, while also decreasing MAP. Rosiglitazone diminished the
      increase in HR, decreased the markers of organ injury (GOT, GPT, BUN, Cre, LDH,
      CPK, glucose) and inflammatory biomarkers (TNF-alpha, IL-6), and did not affect
      MAP after LPS. In conclusion, rosiglitazone ameliorated endotoxin shock-induced
      markers of organ injury and suppressed the release of TNF-alpha and IL-6 in
      conscious rats.

PMID- 20034950
TI  - Integrated review of cytokines in maternal, cord, and newborn blood: part I-
      associations with preterm birth.
AB  - Preterm birth (PTB; spontaneous delivery prior to 37 weeks gestation) affects one
      out of eight infants born in the United States and is the most common cause of
      neonatal morbidity and mortality. Although the pathogenesis of PTB is
      multifactorial, a growing body of literature supports the hypothesis that one
      cause of PTB is inflammation in pregnancy. Investigators have implicated
      mediators of inflammation, most notably proinflammatory cytokines, as being
      associated with and perhaps a playing a causal role in the pathogenesis of
      preterm labor and adverse early fetal outcomes. Though researchers have pursued
      the association of cytokines with preterm labor and subsequent early adverse
      fetal outcomes as a line of research, there has been little integration of
      diverse findings across studies. This systematic review appraises the empirical
      evidence from human studies for the association of levels of cytokines in blood
      with preterm labor and adverse early fetal outcome to examine the current state
      of the science in this important area of biobehavioral research. The most
      consistent finding is that increased levels of proinflammatory cytokines,
      particularly interleukin (IL) 6, IL-beta1, and tumor necrosis factor alpha (TNF
      alpha), are associated with PTB as compared to levels found at term birth.
      However, there have been relatively few studies and results have not been
      consistent. Therefore, further research is needed to elucidate the association of
      these inflammatory mediators with adverse pregnancy outcomes.

PMID- 20034951
TI  - Clostridium difficile infection in the intensive care unit.
AB  - Clostridium difficile infection (CDI) is an increasing nosocomial problem in
      North America and Western Europe, where outbreaks caused by a more virulent,
      toxin-hyperproducing strain have been recently reported. Clostridium difficile
      infection is now characterized by a higher incidence, more frequent relapses, and
      a higher case-fatality ratio. As a consequence, fulminant cases requiring
      admission to the intensive care unit (ICU) are much more common than previously.
      In recent years, metronidazole has appeared to lose some of its effectiveness in
      CDI management and vancomycin is now recognized as the first-line treatment of
      severe cases. Rapid diagnosis and institution of infection control measures are
      critical components of CDI management. The current review focuses on recent
      changes in the epidemiology, diagnostic methods, and treatment of CDI, with
      special emphasis on complicated cases managed in the ICU.

PMID- 20034952
TI  - Universal consent practice in academic intensive care units (ICUs).
AB  - The purpose of this study was to determine national practice for obtaining
      consent in academic adult intensive care units (ICUs) for routine bedside
      procedures and to define universal consent rates by patient demographics within
      our own institution's ICUs. METHODS: A 10-question survey was sent to the program
      directors for all U.S. surgical and pulmonary critical care directors regarding
      consent practices. Further, the adoption of a universal consent protocol in an
      academic county hospital was studied. RESULTS: Cross-sectional study: Thirty
      seven percent of program directors completed the survey. Consent rates varied
      from 35% to 97% by procedure, with only 14% using a universal consent document.
      Providers in Medical ICUs obtained consent more often than in Surgical ICUs for
      both central line and pulmonary artery catheter placement (82.8% and 93.1% vs.
      52.6% and 52.6%, respectively). Prospective cohort study: At our institution, 90%
      of 363 patients or their proxies signed universal consent for procedures, 4.4%
      consent with exemptions, while 5.2% refused. Insured patients were 2.7 times more
      likely to sign full universal consent for bedside ICU procedures than uninsured
      patients. CONCLUSION: There was a national variation in ICU consent practices
      with an interest in a wider usage of universal consent protocols. The latter was
      adopted differentially based on patient demographics. Universal consent was
      widely accepted at our institution.

PMID- 20034953
TI  - Glycemic control in critically ill patients before and after institution of an
      intensive insulin infusion protocol: circadian rhythm and the quality duration
      calculator.
AB  - INTRODUCTION: A circadian rhythm of blood glucose values has been recently
      reported in critically ill patients, but there are no reports of how this rhythm
      is altered by a continuous intensive insulin infusion therapy protocol (IIT). We
      wished to examine the effect of IIT on this rhythm as well as to describe the use
      of the quality duration calculator (QDC) for the evaluation of glycemic control
      before and after IIT. METHODS: This was a retrospective multihospital
      observational study that took place in the medical and surgical intensive care
      units (ICUs) of 2 tertiary care hospitals. Cohorts of consecutively admitted
      critically ill patients from 2-year periods before and after institution of an
      IIT protocol were examined. Laboratory, demographic, and outcome data were
      extracted from hospital databases. RESULTS: We studied 167,645 blood glucose
      measurements from 8,327 patients. We observed a circadian rhythm of blood glucose
      control in the pre-IIT cohort that was greatly attenuated in the post-IIT cohort.
      The difference between the morning and the average daily blood glucose in the pre
      IIT cohort was 3.53 mg/dL (P < .001), and the difference between these values in
      the post-IIT cohort was 1.10 mg/dL (P = .031). In addition, the circadian nature
      of hyperglycemia incidence observed in the pre-IIT cohort was not seen in the
      post-IIT cohort. The amount of time spent in goal glycemic range increased from
      23.69% (95% CI 23.01-24.38) in the pre-IIT cohort to 29.67% (95% CI 29.04-30.31)
      in the post-IIT cohort as estimated by the QDC. The amount of time spent in the
      hyperglycemic decreased from 20.17% (95% CI 19.33-20.99) in the pre-IIT cohort to
      14.80% (95% CI 14.15-15.39) in the post-IIT cohort. CONCLUSIONS: The circadian
      rhythm of blood glucose control confirmed in our pre-IIT cohort was lost after
      institution of IIT. The morning blood glucose value appears to be a reasonable
      surrogate of overall glycemic control in a critically ill population on IIT,
      although this may vary based on the degree of control achieved. The QDC method is
      useful for analyzing glycemic control in patients on IIT.

PMID- 20034954
TI  - Epstein-Barr virus DNase (BGLF5) induces genomic instability in human epithelial
      cells.
AB  - Epstein-Barr Virus (EBV) DNase (BGLF5) is an alkaline nuclease and has been
      suggested to be important in the viral life cycle. However, its effect on host
      cells remains unknown. Serological and histopathological studies implied that EBV
      DNase seems to be correlated with carcinogenesis. Therefore, we investigate the
      effect of EBV DNase on epithelial cells. Here, we report that expression of EBV
      DNase induces increased formation of micronucleus, an indicator of genomic
      instability, in human epithelial cells. We also demonstrate, using gammaH2AX
      formation and comet assay, that EBV DNase induces DNA damage. Furthermore, using
      host cell reactivation assay, we find that EBV DNase expression repressed damaged
      DNA repair in various epithelial cells. Western blot and quantitative PCR
      analyses reveal that expression of repair-related genes is reduced significantly
      in cells expressing EBV DNase. Host shut-off mutants eliminate shut-off
      expression of repair genes and repress damaged DNA repair, suggesting that shut
      off function of BGLF5 contributes to repression of DNA repair. In addition, EBV
      DNase caused chromosomal aberrations and increased the microsatellite instability
      (MSI) and frequency of genetic mutation in human epithelial cells. Together, we
      propose that EBV DNase induces genomic instability in epithelial cells, which may
      be through induction of DNA damage and also repression of DNA repair,
      subsequently increases MSI and genetic mutations, and may contribute consequently
      to the carcinogenesis of human epithelial cells.

PMID- 20034956
TI  - Structural motifs of the bacterial ribosomal proteins S20, S18 and S16 that
      contact rRNA present in the eukaryotic ribosomal proteins S25, S26 and S27A,
      respectively.
AB  - The majority of constitutive proteins in the bacterial 30S ribosomal subunit have
      orthologues in Eukarya and Archaea. The eukaryotic counterparts for the remainder
      (S6, S16, S18 and S20) have not been identified. We assumed that amino acid
      residues in the ribosomal proteins that contact rRNA are to be constrained in
      evolution and that the most highly conserved of them are those residues that are
      involved in forming the secondary protein structure. We aligned the sequences of
      the bacterial ribosomal proteins from the S20p, S18p and S16p families, which
      make multiple contacts with rRNA in the Thermus thermophilus 30S ribosomal
      subunit (in contrast to the S6p family), with the sequences of the unassigned
      eukaryotic small ribosomal subunit protein families. This made it possible to
      reveal that the conserved structural motifs of S20p, S18p and S16p that contact
      rRNA in the bacterial ribosome are present in the ribosomal proteins S25e, S26e
      and S27Ae, respectively. We suggest that ribosomal protein families S20p, S18p
      and S16p are homologous to the families S25e, S26e and S27Ae, respectively.

PMID- 20034955
TI  - The N-terminus of hTERT contains a DNA-binding domain and is required for
      telomerase activity and cellular immortalization.
AB  - Telomerase defers the onset of telomere damage-induced signaling and cellular
      senescence by adding DNA onto chromosome ends. The ability of telomerase to
      elongate single-stranded telomeric DNA depends on the reverse transcriptase
      domain of TERT, and also relies on protein:DNA contacts outside the active site.
      We purified the N-terminus of human TERT (hTEN) from Escherichia coli, and found
      that it binds DNA with a preference for telomeric sequence of a certain length
      and register. hTEN interacted with the C-terminus of hTERT in trans to
      reconstitute enzymatic activity in vitro. Mutational analysis of hTEN revealed
      that amino acids Y18 and Q169 were required for telomerase activity in vitro, but
      not for the interaction with telomere DNA or the C-terminus. These mutants did
      not reconstitute telomerase activity in cells, maintain telomere length, or
      extend cellular lifespan. In addition, we found that T116/T117/S118, while
      dispensable in vitro, were required for cellular immortalization. Thus, the
      interactions of hTEN with telomere DNA and the C-terminus of hTERT are
      functionally separable from the role of hTEN in telomere elongation activity in
      vitro and in vivo, suggesting other roles for the protein and nucleic acid
      interactions of hTEN within, and possibly outside, the telomerase catalytic core.

PMID- 20034957
TI  - The prevalence and outcome of excess body weight among Middle Eastern patients
      presenting with acute coronary syndrome.
AB  - We evaluated the effect of body weight on the outcome of Middle Eastern patients
      presenting with acute coronary syndrome (ACS). Analysis of the Gulf Registry of
      Acute Coronary Events (Gulf RACE) survey that included 7843 consecutive patients
      hospitalized with ACS was made. Patients were categorized as normal weight,
      overweight, or obese based on their body mass index (BMI). Overall, 67% of
      patients were overweight or obese; obese and overweight patients were more likely
      to be female and have diabetes mellitus, hypertension, dyslipidemia, and less
      likely to be smokers. In-hospital mortality, congestive heart failure,
      cardiogenic shock, and strokes were comparable between the groups, although
      patients with obesity were more likely to have recurrent ischemia and major
      bleeding complication in the ST-elevation myocardial infarction group. Excess
      body weight with ACS is associated with higher risk profile characteristics
      without an increase in hospital mortality or cardiovascular events.

PMID- 20034958
TI  - Radial artery catheterization for percutaneous vascular or coronary
      interventions: an innocent procedure?

PMID- 20034959
TI  - Cardiovascular risk factors and estimated 10-year risk of fatal cardiovascular
      events using various equations in Greeks with metabolic syndrome.
AB  - We investigated cardiovascular disease (CVD) risk factors in 1501 Greeks (613 men
      and 888 women, aged 40-65 years) referred to outpatients with metabolic syndrome
      (MetS) and without diabetes mellitus or CVD. The 10-year risk of fatal CVD events
      was calculated using European Society of Cardiology Systematic Coronary Risk
      Estimation (ESC SCORE), Hellenic-SCORE, and Framingham equations. Raised blood
      pressure (BP) and hypertriglyceridemia were more common in men (89.6% vs 84.2%
      and 86.8% vs 74.2%, respectively; P < .001). Low high-density lipoprotein
      cholesterol (HDL-C) and abdominal obesity were more common in women (58.2% vs
      66.2% and 85.8% vs 97.1%, respectively; P < .001). The 10-year risk of fatal CVD
      events using HellenicSCORE was higher in men (6.3% +/- 4.3% vs 2.7% +/- 2.1%; P <
      .001). European Society of Cardiology Systematic Coronary Risk Estimation and
      Framingham yielded similar results. The risk equations gave similar assessments
      in a European Mediterranean population except for HellenicSCORE that calculated
      more MetS women requiring risk modification. This might justify local risk engine
      evaluation in event-based studies. (Clinical-Trials.gov ID: NCT00416741).

PMID- 20034960
TI  - Earth to JUPITER: how a potent statin may actually be detrimental for lifestyle
      associated diseases.

PMID- 20034961
TI  - Moderate oxygen augments lipopolysaccharide-induced lung injury in mice.
AB  - Despite the associated morbidity and mortality, underlying mechanisms leading to
      the development of acute lung injury (ALI) remain incompletely understood.
      Frequently, ALI develops in the hospital, coinciding with institution of various
      therapies, including the use of supplemental oxygen. Although pathological
      evidence of hyperoxia-induced ALI in humans has yet to be proven, animal studies
      involving high oxygen concentration reproducibly induce ALI. The potentially
      injurious role of lower and presumably safer oxygen concentrations has not been
      well characterized in any species. We hypothesized that in the setting of a
      preexisting insult to the lung, the addition of moderate-range oxygen can augment
      lung injury. Our model of low-dose intratracheal LPS (IT LPS) followed by 60%
      oxygen caused a significant increase in ALI compared with LPS or oxygen alone
      with increased alveolar neutrophils, histological injury, and epithelial barrier
      permeability. In the LPS plus oxygen group, regulatory T cell number was reduced,
      and macrophage activation markers were increased, compared with LPS alone.
      Antibody-mediated depletion of neutrophils significantly abrogated the observed
      lung injury for all measured factors. The enhanced presence of alveolar
      neutrophils in the setting of LPS and oxygen is due, at least in part, to
      elevated chemokine gradients signaling neutrophils to the alveolar space. We
      believe these results strongly support an effect of lower concentrations of
      oxygen to augment the severity of a mild preexisting lung injury and warrants
      further investigation in both animals and humans.

PMID- 20034962
TI  - Therapeutic effect of lecithinized superoxide dismutase on bleomycin-induced
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is thought to involve inflammatory
      infiltration of leukocytes, lung injury induced by reactive oxygen species (ROS),
      in particular superoxide anion, and fibrosis (collagen deposition). No treatment
      has been shown to improve definitively the prognosis for IPF patients. Superoxide
      dismutase (SOD) catalyzes the dismutation of superoxide anion to hydrogen
      peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD)
      has overcome clinical limitations of SOD, including low tissue affinity and low
      stability in plasma. In this study, we examined the effect of PC-SOD on bleomycin
      induced pulmonary fibrosis. Severity of the bleomycin-induced fibrosis in mice
      was assessed by various methods, including determination of hydroxyproline levels
      in lung tissue. Intravenous administration of PC-SOD suppressed the bleomycin
      induced increase in the number of leukocytes in bronchoalveolar lavage fluid.
      Bleomycin-induced collagen deposition and increased hydroxyproline levels in the
      lung were also suppressed in animals treated with PC-SOD, suggesting that PC-SOD
      suppresses bleomycin-induced pulmonary fibrosis. The dose-response profile of PC
      SOD was bell-shaped, but concurrent administration of catalase restored the
      ameliorative effect at high doses of PC-SOD. Intratracheal administration or
      inhalation of PC-SOD also attenuated the bleomycin-induced inflammatory response
      and fibrosis. The bell-shaped dose-response profile of PC-SOD was not observed
      for these routes of administration. We consider that, compared with intravenous
      administration, inhalation of PC-SOD may be a more therapeutically beneficial
      route of administration due to the higher safety and quality of life of the
      patient treated with this drug.

PMID- 20034963
TI  - Mechanisms of suppression of alveolar epithelial cell GM-CSF expression in the
      setting of hyperoxic stress.
AB  - Pulmonary expression of granulocyte/macrophage colony-stimulating factor (GM-CSF)
      is critically important for normal functional maturation of alveolar macrophages.
      We found previously that lung GM-CSF is dramatically suppressed in mice exposed
      to hyperoxia. Alveolar epithelial cells (AEC) are a major source of GM-CSF in the
      peripheral lung, and in vivo hyperoxia resulted in greatly reduced expression of
      GM-CSF protein by AEC ex vivo. We now explore the mechanisms responsible for this
      effect, using primary cultures of murine AEC exposed to hyperoxia in vitro.
      Exposure of AEC to 80% oxygen/5% CO(2) for 48 h did not induce overt toxicity,
      but resulted in significantly decreased GM-CSF protein and mRNA expression
      compared with cells in normoxia. Similar effects were seen when AEC were stressed
      with serum deprivation, an alternative inducer of oxidative stress. The effects
      in AEC were opposite those in a murine lung epithelial cell line (MLE-12 cells),
      in which hyperoxia induced GM-CSF expression. Both hyperoxia and serum
      deprivation resulted in increased intracellular reactive oxygen species (ROS) in
      AEC. Hyperoxia and serum deprivation induced significantly accelerated turnover
      of GM-CSF mRNA. Treatment of AEC with catalase during oxidative stress preserved
      GM-CSF protein and mRNA and was associated with stabilization of GM-CSF mRNA. We
      conclude that hyperoxia-induced suppression of AEC GM-CSF expression is a
      function of ROS-induced destabilization of GM-CSF mRNA. We speculate that AEC
      oxidative stress results in significantly impaired pulmonary innate immune
      defense due to effects on local GM-CSF expression in the lung.

PMID- 20034964
TI  - Low glucose uncouples hexokinase1-dependent sugar signaling from stress and
      defense hormone abscisic acid and C2H4 responses in Arabidopsis.

PMID- 20034965
TI  - A PIP1 aquaporin contributes to hydrostatic pressure-induced water transport in
      both the root and rosette of Arabidopsis.
AB  - Aquaporins are channel proteins that facilitate the transport of water across
      plant cell membranes. In this work, we used a combination of pharmacological and
      reverse genetic approaches to investigate the overall significance of aquaporins
      for tissue water conductivity in Arabidopsis (Arabidopsis thaliana). We addressed
      the function in roots and leaves of AtPIP1;2, one of the most abundantly
      expressed isoforms of the plasma membrane intrinsic protein family. At variance
      with the water transport phenotype previously described in AtPIP2;2 knockout
      mutants, disruption of AtPIP1;2 reduced by 20% to 30% the root hydrostatic
      hydraulic conductivity but did not modify osmotic root water transport. These
      results document qualitatively distinct functions of different PIP isoforms in
      root water uptake. The hydraulic conductivity of excised rosettes (K(ros)) was
      measured by a novel pressure chamber technique. Exposure of Arabidopsis plants to
      darkness increased K(ros) by up to 90%. Mercury and azide, two aquaporin
      inhibitors with distinct modes of action, were able to induce similar inhibition
      of K(ros) by approximately 13% and approximately 25% in rosettes from plants
      grown in the light or under prolonged (11-18 h) darkness, respectively. Prolonged
      darkness enhanced the transcript abundance of several PIP genes, including
      AtPIP1;2. Mutant analysis showed that, under prolonged darkness conditions,
      AtPIP1;2 can contribute to up to approximately 20% of K(ros) and to the osmotic
      water permeability of isolated mesophyll protoplasts. Therefore, AtPIP1;2 can
      account for a significant portion of aquaporin-mediated leaf water transport. The
      overall work shows that AtPIP1;2 represents a key component of whole-plant
      hydraulics.

PMID- 20034966
TI  - Evolution and history of grapevine (Vitis vinifera) under domestication: new
      morphometric perspectives to understand seed domestication syndrome and reveal
      origins of ancient European cultivars.
AB  - BACKGROUND AND AIMS: In spite of the abundance of archaeological, bio
      archaeological, historical and genetic data, the origins, historical
      biogeography, identity of ancient grapevine cultivars and mechanisms of
      domestication are still largely unknown. Here, analysis of variation in seed
      morphology aims to provide accurate criteria for the discrimination between wild
      grapes and modern cultivars and to understand changes in functional traits in
      relation to the domestication process. This approach is also used to quantify the
      phenotypic diversity in the wild and cultivated compartments and to provide a
      starting point for comparing well-preserved archaeological material, in order to
      elucidate the history of grapevine varieties. METHODS: Geometrical analysis
      (elliptic Fourier transform method) was applied to grapevine seed outlines from
      modern wild individuals, cultivars and well-preserved archaeological material
      from southern France, dating back to the first to second centuries. KEY RESULTS
      AND CONCLUSIONS: Significant relationships between seed shape and taxonomic
      status, geographical origin (country or region) of accessions and parentage of
      varieties are highlighted, as previously noted based on genetic approaches. The
      combination of the analysis of modern reference material and well-preserved
      archaeological seeds provides original data about the history of ancient
      cultivated forms, some of them morphologically close to the current 'Clairette'
      and 'Mondeuse blanche' cultivars. Archaeobiological records seem to confirm the
      complexity of human contact, exchanges and migrations which spread grapevine
      cultivation in Europe and in Mediterranean areas, and argue in favour of the
      existence of local domestication in the Languedoc (southern France) region during
      Antiquity.

PMID- 20034967
TI  - Minimal local anaesthetic volumes for sciatic nerve block: evaluation of ED 99 in
      volunteers.
AB  - BACKGROUND: This randomized, double-blinded volunteer study was designed to
      evaluate the ED(99) volume of local anaesthetic for sciatic nerve blocks using a
      step-up/step-down methodology. METHODS: A maximum of 20 volunteers were included
      to receive an ultrasound-guided sciatic nerve block with mepivacaine 1.5% and a
      starting volume of 0.2 ml mm(-2) cross-sectional nerve area. In cases of a
      complete sensory block, the volume was reduced by 0.02 ml mm(-2) cross-sectional
      nerve area until the first block failed. Thereafter, the volume of local
      anaesthetic was increased by 0.02 ml mm(-2) cross-sectional nerve area. After
      three cycles of successful/failed blocks, the ED(99) volume of local anaesthetic
      could be calculated by a probability function. The influence of the volumes of
      local anaesthetics on sensory onset times and duration of sensory block was
      evaluated by linear regression. RESULTS: The ED(99) volume of local anaesthetic
      for sciatic nerve block was calculated with 0.10 ml mm(-2) cross-sectional nerve
      area. The correlation between the volume of local anaesthetic and the sensory
      onset time was weak (r=0.14), whereas the correlation between the volume of local
      anaesthetic and the duration of sensory block was moderate (r=0.65). CONCLUSIONS:
      This is the first study where an ED(99) volume of local anaesthetic for sciatic
      nerve block has been evaluated. The resulting local anaesthetic volume of 0.10 ml
      mm(-2) cross-sectional nerve area seems to have no impact on sensory onset time,
      whereas the duration of sensory block is shorter.

PMID- 20034968
TI  - Bilateral partial lung lavage in an infant with pulmonary alveolar proteinosis.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease in infancy, resulting from
      abnormalities of surfactant production or decreased catabolism of surfactant. The
      only effective treatment of the congenital form of PAP is bronchoalveolar lavage.
      A 4-month-old boy with severe PAP received bilateral partial lung lavage on two
      occasions resulting in clinical improvement. We performed partial lung lavage
      using a 3.1 mm flexible fibreoptic bronchoscope introduced through a 4.0 mm
      tracheal tube under general anaesthesia. The infant did not require extra
      corporeal oxygenation during the procedure or postoperative ventilation. This
      method may offer a feasible option for performing lavage in a resource
      constrained environment.

PMID- 20034971
TI  - Acute coronary syndrome in a patient with acquired immunodeficiency syndrome and
      non-bacterial thrombotic endocarditis.

PMID- 20034972
TI  - Risk prediction is improved by adding markers of subclinical organ damage to
      SCORE.
AB  - AIMS: It is unclear whether subclinical vascular damage adds significantly to
      Systemic Coronary Risk Evaluation (SCORE) risk stratification in healthy
      subjects. METHODS AND RESULTS: In a population-based sample of 1968 subjects
      without cardiovascular disease or diabetes not receiving any cardiovascular, anti
      diabetic, or lipid-lowering treatment, aged 41, 51, 61, or 71 years, we measured
      traditional cardiovascular risk factors, left ventricular (LV) mass index,
      atherosclerotic plaques in the carotid arteries, carotid/femoral pulse wave
      velocity (PWV), and urine albumin/creatinine ratio (UACR) and followed them for a
      median of 12.8 years. Eighty-one subjects died because of cardiovascular causes.
      Risk of cardiovascular death was independently of SCORE associated with LV
      hypertrophy [hazard ratio (HR) 2.2 (95% CI 1.2-4.0)], plaques [HR 2.5 (1.6-4.0)],
      UACR > or = 90th percentile [HR 3.3 (1.8-5.9)], PWV > 12 m/s [HR 1.9 (1.1-3.3)
      for SCORE > or = 5% and 7.3 (3.2-16.1) for SCORE < 5%]. Restricting primary
      prevention to subjects with SCORE > or = 5% as well as subclinical organ damage,
      increased specificity of risk prediction from 75 to 81% (P < 0.002), but reduced
      sensitivity from 72 to 65% (P = 0.4). Broaden primary prevention from subjects
      with SCORE > or = 5% to include subjects with 1% < or = SCORE < 5% together with
      subclinical organ damage increased sensitivity from 72 to 89% (P = 0.006), but
      reduced specificity from 75 to 57% (P < 0.002) and positive predictive value from
      11 to 8% (P = 0.07). CONCLUSION: Subclinical organ damage predicted
      cardiovascular death independently of SCORE and the combination may improve risk
      prediction.

PMID- 20034973
TI  - Prognostic utility of quantifying evolutionary ST-segment depression on early
      follow-up electrocardiogram in patients with non-ST-segment elevation acute
      coronary syndromes.
AB  - AIMS: Although ST-segment depression (STD) on the admission electrocardiogram
      (ECG) confers adverse prognosis in patients with non-ST-segment elevation acute
      coronary syndromes (NSTE-ACS), the implications of STD on follow-up ECG remain
      uncertain. We determined the prognostic significance of STD on follow-up ECG
      performed within 12-24 h of admission and whether its quantitative evaluation can
      further refine risk stratification. METHODS AND RESULTS: The admission and follow
      up ECGs of 3877 patients in the SYNERGY trial were analysed for the presence
      (>or=1 mm) and extent (maximum magnitude on any single lead) of STD. Of the 1110
      patients presenting with STD on admission, 534 (48.1%) with persistent STD at
      follow-up had higher mortality at 30 days (7.1 vs. 3.6%, P = 0.01) and 6 months
      (10.7 vs. 5.2%, P = 0.001) than those with normalized STD. Among 2767 patients
      without STD on admission, 174 (6.3%) developed new STD on follow-up ECG and
      experienced increased mortality compared with those without such interval change
      (30 days: 4.0 vs. 1.7%, P = 0.035; 6 months: 8.0 vs. 3.3%, P = 0.001). After
      adjustment for established clinical prognosticators and the extent of STD on
      admission, every 1 mm increment of STD on the follow-up ECG independently
      predicted a graded increase in 30-day mortality [hazards ratio (HR) = 1.60, 95%
      confidence interval (CI) = 1.29-1.98, P < 0.0001], and death/myocardial
      infarction at 30 days (HR = 1.19, 95% CI = 1.03-1.36, P = 0.017) and 6 months (HR
      = 1.17, 95% CI = 1.03-1.32, P = 0.016). CONCLUSION: The magnitude of STD on a
      routine 12-24 h follow-up ECG provides incremental prognostic information beyond
      established clinical prognosticators and the extent of STD on admission.
      Incorporating a follow-up ECG and its quantitative evaluation for STD may further
      refine risk stratification of patients with NSTE-ACS.

PMID- 20034974
TI  - Identical anatomical location of accessory pathway in a family with Wolff
      Parkinson-White syndrome.
AB  - Identical location of accessory pathways in family members with Wolff-Parkinson
      White syndrome, although theoretically possible, has never been described. A 37
      year-old woman and her 18-year-old son were referred for electrophysiological
      study due to fast rate palpitations and pre-excitation on baseline
      electrocardiogram. After mapping during pre-excitation, successful radiofrequency
      application was located at the right free wall in both patients, in an identical
      anatomical position, on the infero-lateral aspect of the tricuspid ring.

PMID- 20034975
TI  - Is the use of an additional pace/sense lead the optimal strategy for the
      avoidance of lead extraction in defibrillation lead failure? A single-centre
      experience.
AB  - AIMS: The implantation of an additional pace-sense (P/S) lead is a standard
      treatment option in the management of an isolated pace-sense problem in a
      defibrillation (HV-P/S) lead. However, the safety of this management strategy is
      unclear. We performed a retrospective single-centre study to assess this. METHODS
      AND RESULTS: We studied all patients with an isolated P/S problem in an HV-P/S
      lead, treated with an additional P/S lead, in our institution. The need for
      further invasive intervention for a lead-related complication, or death during
      follow-up, was assessed. From 2000 to 2008, 45 patients were treated with an
      additional P/S lead. Mean follow-up was 78 +/- 38 months from original device
      implantation and 28 +/- 17 months following implantation of the additional lead.
      During follow-up, three patients required an invasive intervention for a lead
      related problem. All were successfully treated with lead extraction and device re
      implantation. There were five deaths. Following implant of an additional lead,
      cumulative survival from further lead defects after 6 months, 1, 2, and 3 years
      was 100, 100, 93, and 87%, respectively. CONCLUSION: In the treatment of an
      isolated P/S problem in an HV-P/S lead, the placement of an additional P/S lead
      is a safe management strategy, at least in the short term.

PMID- 20034976
TI  - Suitability of three saws for minimally invasive bone cutting.
AB  - This study compares 3 different saw types to determine which is best suited for
      integration into a minimally invasive bone saw. A handheld electric jigsaw, a
      coping saw, and a Gigli saw were used to cut into porcine ilium. Heat generated
      was measured using a thermocouple, and forces applied during cutting were
      recorded using a force/torque sensor. The coping saw generated an average maximum
      temperature that was 26 degrees C less than that generated using the jigsaw (P <
      .001) and 14 degrees C less than that for the Gigli saw (P < .001). On average,
      the maximum force applied through the coping saw was 14 N less than that through
      the jigsaw (P < .001) and 18 N less than that through the Gigli saw (P < .001).
      Out of the 3 saws tested, the coping saw is optimal for cutting bone based on
      heat generation and required force.

PMID- 20034977
TI  - Angiolipoma of the breast in a male: a case report and review of the literature.
AB  - OBJECTIVE: Angiolipoma is an unusual variant of lipoma involving subcutaneous
      tissues on trunk and extremities. This tumor is rarely described in the breast
      and particularly in breast male. CASE REPORT: We report here the case of
      angiolipoma of the breast in a 55-year-old man complained of tenderness in the
      left breast. Ultrasonography showed a homogenously, well circumscribed,
      hyperechoic mass in the internal quadran of breast. The surgically resected tumor
      showed mature fat cells separated by proliferating branched vessels and
      intravascular hyaline thrombi. CONCLUSION: The existence of angiolipoma of the
      breast in the male must not to be forgotten because this tumor may be confused
      clinically, radiologically and pathologically with a malignant tumor.

PMID- 20034978
TI  - Nest-like features in bladder, simulating the nested variant of urothelial
      carcinoma.
AB  - Nest-like structures are the cardinal lesion of different benign and malignant
      bladder entities. These entities emphasize the biological relevance of the subtle
      morphological nest plasticity. The authors present 25 benign and malignant
      neoplasms, sharing the presence of florid nest-like growth and the scarcity or
      absence of superficial papillary components. Differential diagnostic clues are
      discussed.

PMID- 20034979
TI  - Neoplasms with schwannian differentiation express transcription factors known to
      regulate normal schwann cell development.
AB  - A number of transcription factors have been identified as important in guiding
      normal Schwann cell development. This study used immunohistochemistry on tissue
      arrays to assess the expression of some of these transcription factors (Sox5,
      Sox9, Sox10, AP-2alpha, Pax7, and FoxD3) on 76 schwannomas, 105 neurofibromas,
      and 34 malignant peripheral nerve sheath tumors (MPNSTs). Sox9 and Sox10 were
      found to be widely expressed in all tumor types. FoxD3 reactivity was stronger
      and more frequently found in schwannomas and MPNSTs than neurofibromas. AP-2alpha
      was positive in 31% to 49% of all tumors, but strong reactivity was limited to
      MPNSTs and schwannomas. Pax7 and Sox5 expression was restricted to subsets of
      MPNSTs. Statistical analysis showed significant differences between the 3 tumor
      types in the expression of these markers. No differences were found in the
      analyzed tumor subgroups, including schwannomas of different sites, schwannomas
      with or without NF2 association, neurofibromas of different types, or sporadic
      versus NF1-associated MPNSTs. These results suggest that the transcription
      factors that guide normal Schwann cell development also play a role in the
      biology of neoplastic cells with Schwannian differentiation. FoxD3, AP-2alpha,
      Pax7, and Sox5 are upregulated in MPNSTs compared with neurofibromas and may be
      markers of malignant transformation. Screening the expression of FoxD3, Sox9, and
      Sox10 on 23 cases of other spindle-cell proliferations that may be considered in
      the differential diagnosis of MPNST, including synovial sarcoma and spindle cell
      melanoma, suggests that these 3 are helpful markers of Schwannian differentiation
      in the context of diagnosing MPNSTs.

PMID- 20034980
TI  - Renal cell carcinoma in children and young adults: clinicopathological,
      immunohistochemical, and VHL gene analysis of 46 cases with follow-up.
AB  - To further study the characteristics of renal cell carcinoma (RCC) in young
      patients and better define their biological features, 46 RCCs of patients younger
      than 25 years were morphologically and immunohistochemically characterized with
      follow-up. Loss of heterozygosity (LOH) analysis of the von Hippel-Lindau (VHL)
      gene region and screening for VHL gene mutations were performed in all tumors.
      Applying the 2004 WHO classification for RCC, there were 19 Xp11.2 translocation
      RCCs, 9 clear cell RCCs, 17 papillary RCCs, and 1 unclassified RCC. All 19 Xp11.2
      translocation RCCs showed moderate to strong immunoreactivity for TFE3. None had
      TFEB immunoreactivity. One Xp11.2 translocation RCC had an unreported morphology
      with empty or ground glass nuclei, occasional nuclear grooves, inconspicuous
      nucleoli and abundant mucinous material in stroma.VHL gene analysis revealed
      deletions at 3p25-26 in 1 clear cell RCC and 1 papillary type 2 RCC. The
      papillary type 2 RCC was also presented with a family history of VHL disease and
      found a germline mutation G -> C on a splicing site at position 553+5. The
      present case widens the spectrum of microscopic features to be found in VHL
      associated RCC. There were no VHL mutations in the remaining 45 RCCs. Statistical
      analysis of stage and outcome revealed that TFE+ pediatric RCCs were
      significantly more frequently associated with a higher pTNM pT3/pT4 stage and a
      poorer outcome than TFE-RCCs (P < .05). Owing to the already known aggressive
      behavior of these Xp11.2 translocation RCCs, patients with TFE+ pediatric RCCs
      should benefit from a stricter follow-up.

PMID- 20034981
TI  - Primary yolk sac tumor of the urachus.
AB  - INTRODUCTION: Neoplasms originating from the urachus are rare. The most common
      urachal malignancy is adenocarcinoma, whereas extragonadal germ cell tumors,
      primarily of the urachus, are an extremely rare finding. OBJECTIVE: To describe a
      primary yolk sac tumor (YST) of the urachus in an adult. CASE REPORT: A 44-year
      old woman presented with 6 months of pelvic pain associated with a sensation of
      progressive mass growth. At the time of tumor resection, the tumor was found to
      be attached by a pedicle to the dome of the bladder, with no injury to the
      adjacent organs. Pathological study showed a neoplasm with epithelioid cells,
      pseudocysts, a myxomatous background, and Schiller-Duval body formations.
      Immunohistochemistry stains showed positivity to AE1/AE3, alpha-1-fetoprotein,
      and alpha-1-antitrypsin and negativity to other markers. CONCLUSION: An unusual
      case of a YST in the urachus is presented. This is the first reported adult case
      based on the authors' bibliographic search.

PMID- 20034982
TI  - EBV-associated polymorphic posttransplant lymphoproliferative disorder presenting
      as gingival ulcers.
AB  - Posttransplant lymphoproliferative disorders (PTLDs) present a wide
      clinicopathological spectrum, varying from the usual Epstein-Barr virus (EBV)
      driven infectious mononucleosis-type polyclonal proliferations to EBV-positive or
      EBV-negative proliferations indistinguishable from overt lymphomas that occur in
      immunocompetent individuals. PTLDs characteristically have a predilection for
      extranodal sites and association with EBV.These disorders are usually B-cell
      type, although T-cell and rare cases involving both T- and B-cell types have also
      been described. The initial treatment consists in decreasing the immnosupressive
      therapy, usually with favorable results. The authors report on a rare case of a
      19-year-old girl, with post-renal transplantation EBV-associated polymorphic
      lymphoproliferative gingival ulcerated lesions. To the best of their knowledge,
      this is the first case described in the English-language literature of
      polymorphic PTLD involving both B-cell and T-cell lineages, with an unusual
      immunoprofile affecting the mouth. The authors warn that this condition could be
      easily misdiagnosed as malignant lymphoma if not properly recognized.

PMID- 20034983
TI  - Thyroid-type solid cell nests in struma ovarii.
AB  - Solid cell nests (SCNs) of the thyroid are single or multiple foci of solid
      and/or cystic clusters of squamoid cells (main cells) with a minor proportion of
      C-cells, found in the normal thyroid. The SCNs have also been reported in the
      heart as an ultimobranchial heterotopia. Here, the authors describe a case of
      thyroid-type SCNs associated with struma ovarii. Main cells were positive for
      simple and stratified epithelial-type cytokeratins, carcinoembryonic antigen,
      carbohydrate antigen 19.9, p63, bcl-2, and galectin-3. The neuroendocrine cell
      population was positive for chromogranin A and synaptophysin but negative for
      calcitonin, suggesting a common ancestor cell capable of dual differentiation
      toward thyroid follicular cells and hindgut-type endocrine cells. The existence
      of thyroid-type SCNs in struma ovarii could be easily understood by considering
      the struma ovarii as a teratoma; at the same time, these findings also support
      the idea of a close histogenetic link between the main cells of SCNs and thyroid
      tissue.

PMID- 20034984
TI  - Sarcomatoid thymic carcinoma arising in metaplastic thymoma: a case report.
AB  - Metaplastic thymoma is an extremely rare tumor. To date, only 17 cases of
      metaplastic thymoma have been reported. To the best of the authors' knowledge,
      this is the second reported case of a sarcomatoid carcinoma arising in
      metaplastic thymoma; the carcinoma in this case is larger than that in the
      previous case. A 63-year-old woman with cough and asthenia for 2 weeks was
      admitted to the hospital. Computed tomography (CT) revealed a giant mass on the
      right side of the front mediastinum medium. The mediastinal tumor was excised,
      and additional pathological examinations, immunohistochemical tests, and electron
      microscopic tests were performed. The tumor was diagnosed as a sarcomatoid
      carcinoma arising in metaplastic thymoma. Here, the authors discuss the clinical
      pathology of the sarcomatoid carcinoma arising in metaplastic thymoma and
      describe the biological behaviors with respect to the pathological features.

PMID- 20034985
TI  - Pancytopenia due to massive bone marrow involvement in a patient with primary
      hyperoxaluria.

PMID- 20034986
TI  - NUT midline carcinoma: case report and review of the literature.
AB  - NUT midline carcinoma (NMC) is a recently described, undifferentiated carcinoma
      with specific NUT gene rearrangement, which often involves midline organs such as
      the nasal cavity, paranasal sinuses, mediastinum, or intrathoracic organs. It was
      previously considered a disease of children or young adults, but middle-aged or
      elderly patients have subsequently been seen. Here, the authors report the case
      of a 54-year-old woman who presented with a left-nasal-cavity mass and diplopia.
      The tumor enlarged rapidly and extended to the left orbital cavity and brain base
      despite chemotherapy and radiotherapy. Pathological examination of the resected
      tumor showed an undifferentiated carcinoma with occasional abrupt keratinizing
      squamous differentiation. Immunohistochemical analysis with an antibody to NUT
      revealed that most of the tumor cells were positive. BRD4-NUT gene fusion was
      demonstrated by fluorescence in situ hybridization, confirming the diagnosis of
      NMC. This case emphasizes the importance of considering NMC in the differential
      diagnosis in older adults.

PMID- 20034987
TI  - Malignant transformation in mature cystic teratoma of the ovary: three cases
      mimicking primary ovarian epithelial tumors.
AB  - This study reports 3 unusual cases of malignant transformation in mature cystic
      teratoma of the ovary (dermoid cyst), namely carcinosarcoma, atypical choroid
      plexus papilloma, and papillary thyroid carcinoma, the last case involving both
      ovaries and with peritoneal dissemination. Adequate sampling is essential in such
      ovarian tumors to establish their teratomatous origin and avoid an erroneous
      diagnosis of primary ovarian or metastatic tumors. The authors present the
      clinicopathological findings in these 3 cases with a review of literature.

PMID- 20034988
TI  - Epithelioid sarcoma with heterotopic bone: a morphologic review of 4 cases.
AB  - Epithelioid sarcoma is an uncommon malignancy that usually arises in the
      superficial soft tissues of the extremities. Classically, epithelioid sarcoma
      grows as nodules of mild to moderately atypical epithelioid cells, frequently
      with central necrosis. The stroma is variably fibrous and may rarely contain
      heterotopic bone. The presence of bone within epithelioid sarcoma raises a
      variety of lesions in the differential diagnosis, including reactive processes as
      well as benign and malignant neoplasms.This morphological variant of epithelioid
      sarcoma and its associated diagnostic pitfalls has received little attention in
      the literature. The authors report herein 4 cases of epithelioid sarcoma with
      heterotopic bone and highlight the morphological characteristics of the bone and
      how such variants can be distinguished from other bone-forming lesions of the
      soft tissues.

PMID- 20034989
TI  - beta-Catenin expression in benign and malignant salivary gland tumors.
AB  - OBJECTIVE: To assess the expression of beta-catenin in benign and malignant
      salivary gland tumors and to investigate the possible role of beta-catenin in the
      behavior of salivary gland tumors. STUDY DESIGN: Paraffin embedded tissues from
      45 salivary gland tumors were studied immunohistochemically for expression of
      beta-catenin. RESULT: Reduced/aberrant beta-catenin expression was seen in benign
      and malignant salivary gland tumors. Cytoplasmic localization and reduced
      membranous expression were comparatively observed more in malignant salivary
      gland tumors. Additionally, in pleomorphic adenomas (PAs), beta-catenin exhibited
      intense staining in cells arranged in the form of ducts/tubules, whereas cells in
      clusters and sheets showed weaker immunoreactivity. CONCLUSION: Reduced and
      cytoplasmic localization of beta-catenin could indicate lack of differentiation,
      invasive potential, and aggressive behavior in malignant salivary gland tumors.
      Furthermore, change in expression based on the arrangement of tumor cells may
      suggest that beta-catenin may have a role in morphological variations seen in
      PAs.

PMID- 20034990
TI  - Early colonic perineurioma: a report of 11 cases.
AB  - Colonic perineurioma has been depicted as characterized by a mucosal
      proliferation of monomorphic spindle perineurial cells leading to an evident
      separation, distortion, and entrapment of colonic crypts. The authors, however,
      believe that a sizable subset of the cases differ in that they display only a
      limited perineurial proliferation leading to only mild crypt separation without
      crypt entrapment. This morphological variant (early perineurioma) has not yet
      been documented. The authors herein present the clinicopathological and
      immunohistochemical features of 11 cases. Polyp size ranged from 2 to 4 mm, and 8
      (73%) were located in the sigmoid. Histologically, they revealed small,
      frequently noncontiguous nests or bundles of uniform round to oval cells, causing
      slight separation of parallel or mildly distorted crypts, which displayed a
      serrated/hyperplastic architecture in 8 (73%) cases. Immunostaining for
      perineurial markers showed strong expression for claudin-1, GLUT-1, and collagen
      type IV and weak reactivity for epithelial membrane antigen. In conclusion, early
      perineurioma is a morphological variant of colonic perineurioma in which the
      perineurial proliferation is limited and consequently more difficult to
      recognize. Using perineurial markers is helpful in reaching an accurate
      diagnosis.

PMID- 20034991
TI  - Reading mechanisms in orally educated deaf adults.
AB  - This study was aimed at determining the reading mechanisms used by deaf adults
      who had completed secondary or higher education. Our main hypothesis was that
      they used a reading strategy consisting of identifying (some of) the key words of
      sentences and deriving an overall representation of their meaning. All the
      predictions derived from this hypothesis were supported by the results. In
      addition, an orthographic test showed that they possessed an orthographic lexicon
      richer than hearing group of the same reading level. This is in harmony with the
      key word strategy. Finally, most of the deaf participants (12 out of 14) reached
      scores in metaphonological tasks slightly under the level reached by the hearing
      group. It is speculated that the mechanisms of reading and spelling at play in
      deaf adults are based on phonological representations of words.

PMID- 20034992
TI  - Take-up of Medicare Part D: results from the Health and Retirement Study.
AB  - OBJECTIVES: To estimate the impact of Medicare Part D on prescription drug
      coverage among elderly Medicare beneficiaries and to analyze the predictors of
      program enrollment ("take-up") among those with no prior drug coverage. METHODS:
      Multivariate analyses of data from the 2002, 2004, and 2006 waves of the Health
      and Retirement Study. RESULTS: Take-up of Part D among those without drug
      coverage in 2004 was high; about 50%-60% of this group had Part D coverage in
      2006. Only 7% of senior citizens lacked drug coverage in 2006 compared with 24%
      in 2004. Demand for prescription drugs was the most important determinant of the
      decision to enroll in Part D among those with no prior coverage. Many of those
      who remained without coverage in 2006 reported that they do not use prescribed
      medicines, and the majority had relatively low out-of-pocket spending.
      CONCLUSION: For the most part, Medicare beneficiaries seem to have been able to
      make economically rational decisions about Part D enrollment despite the
      complexity of the program.

PMID- 20034993
TI  - Selective terminations and respect for the disabled.
AB  - It is widely thought that abortion on the grounds of fetal abnormality is morally
      justified. More controversially, Peter Singer has argued that some infants with
      severe disabilities ought to be killed. Many disability rights activists object
      that such claims and practices express disrespect toward disabled persons, even
      if fetuses and infants are only potentially persons. This can seem puzzling. If
      disabled fetuses are not members of the community of disabled persons, how can
      our treatment of the former express disrespect toward the latter? In what
      follows, I shall argue for two claims: first, the he puzzle is only apparent
      because whether we respect someone depends not only on how we do treat him but
      also on how we would treat him were circumstances different, and secondly,
      "substitutionary arguments" for selective terminations of disabled fetuses or
      infants do express disrespect toward disabled persons, even if fetuses and
      infants are only potentially persons.

PMID- 20034994
TI  - Lower incisor intrusion with intraoral transosseous stainless steel wire
      anchorage in rabbits.
AB  - The purpose of this research was to investigate the potential use of intraoral
      transosseous stainless steel wires as anchorage for intrusion of the lower
      incisors using a rabbit model. Placement of intraoral transosseous stainless
      steel wires around incisors is similar to that of intraoral transosseous wiring
      of edentulous mandibular fractures. Ten male New Zealand rabbits, 9 +/- 1.5
      months of age, average weight 1.8 +/- 0.3 kg, were used in this study. One lower
      incisor was intruded with a 50 g bilateral force using a coil spring for 10
      weeks, while the other incisor served as the control. Clinical measurements of
      the distances between the occlusal edges of the incisors (EE) were performed
      weekly with a calliper. In addition to standard descriptive statistical
      calculations, a paired Student's t-test was used for comparison of the two
      groups. All surgical sites healed uneventfully after insertion of the wires.
      Significant differences were found in the change of EE between the experimental
      and control sides from 4 weeks onwards. Intrusion of the incisor, 4 +/- 0.58 mm,
      was seen on the test side, while EE on the control side remained unchanged.
      Within the limits of this animal study, it is concluded that the intraoral
      transosseous stainless steel wire anchorage system is a cost-effective method for
      intrusion of lower incisors when the use of other anchorage system is not
      possible.

PMID- 20034995
TI  - Sickness certification and the GP: what really happens in practice?
AB  - BACKGROUND: GPs typically sanction absence from work by issuing sickness
      certificates. There has been some debate recently about changing the way sickness
      certificates are issued and by whom. However, without understanding GPs'
      certification practices, their requirements in terms of training and education
      and how they feel the certification process should or should not be changed,
      measures aimed at improving the system are unlikely to succeed. OBJECTIVE: To
      investigate and describe British GPs' sickness certification practices. METHODS:
      A cross-sectional nationwide postal survey of 2154 UK GPs was conducted. GPs were
      asked about perceived certification practices, training in sickness
      certification, their opinions about the certification process and potential to
      improve the system. RESULTS: Adjusted response was 42% (n = 878). GPs do ask
      about a patient's work situation but lack training in sickness certification. GPs
      would like to maintain their role in sickness certification but felt there was
      scope for other health professionals to issue some sickness certificates. GPs
      report more frequent sickness certification for mental health and musculoskeletal
      conditions compared to any other condition. CONCLUSIONS: This study has
      highlighted the main issues that GPs face during a consultation where sickness
      certification is a possible outcome. Lack of training in certification was a
      recurrent theme. However, GPs felt there was scope to improve training and
      recommendations were made as to how this might be achieved. The survey has
      highlighted that GPs feel there are opportunities to improve the system and that
      other health professionals may play a role in the certification process.

PMID- 20034996
TI  - Using data-display networks for exploratory data analysis in phylogenetic
      studies.
AB  - Exploratory data analysis (EDA) is a frequently undervalued part of data analysis
      in biology. It involves evaluating the characteristics of the data "before"
      proceeding to the definitive analysis in relation to the scientific question at
      hand. For phylogenetic analyses, a useful tool for EDA is a data-display network.
      This type of network is designed to display any character (or tree) conflict in a
      data set, without prior assumptions about the causes of those conflicts. The
      conflicts might be caused by 1) methodological issues in data collection or
      analysis, 2) homoplasy, or 3) horizontal gene flow of some sort. Here, I explore
      13 published data sets using splits networks, as examples of using data-display
      networks for EDA. In each case, I performed an original EDA on the data provided,
      to highlight the aspects of the resulting network that will be important for an
      interpretation of the phylogeny. In each case, there is at least one important
      point (possibly missed by the original authors) that might affect the
      phylogenetic analysis. I conclude that EDA should play a greater role in
      phylogenetic analyses than it has done.

PMID- 20034997
TI  - Divergence of the mitochondrial genome structure in the apicomplexan parasites,
      Babesia and Theileria.
AB  - Mitochondrial (mt) genomes from diverse phylogenetic groups vary considerably in
      size, structure, and organization. The genus Plasmodium, causative agent of
      malaria, of the phylum Apicomplexa, has the smallest mt genome in the form of a
      circular and/or tandemly repeated linear element of 6 kb, encoding only three
      protein genes (cox1, cox3, and cob). The closely related genera Babesia and
      Theileria also have small mt genomes (6.6 kb) that are monomeric linear with an
      organization distinct from Plasmodium. To elucidate the structural divergence and
      evolution of mt genomes between Babesia/Theileria and Plasmodium, we determined
      five new sequences from Babesia bigemina, B. caballi, B. gibsoni, Theileria
      orientalis, and T. equi. Together with previously reported sequences of B. bovis,
      T. annulata, and T. parva, all eight Babesia and Theileria mt genomes are linear
      molecules with terminal inverted repeats (TIRs) on both ends containing three
      protein-coding genes (cox1, cox3, and cob) and six large subunit (LSU) ribosomal
      RNA (rRNA) gene fragments. The organization and transcriptional direction of
      protein-coding genes and the rRNA gene fragments were completely conserved in the
      four Babesia species. In contrast, notable variation occurred in the four
      Theileria species. Although the genome structures of T. annulata and T. parva
      were nearly identical to those of Babesia, an inversion in the 3-kb central
      region was found in T. orientalis. Moreover, the T. equi mt genome is the largest
      (8.2 kb) and most divergent with unusually long TIR sequences, in which cox3 and
      two LSU rRNA gene fragments are located. The T. equi mt genome showed little
      synteny to the other species. These results suggest that the Theileria mt genome
      is highly diverse with lineage-specific evolution in two Theileria species:
      genome inversion in T. orientalis and gene-embedded long TIR in T. equi.

PMID- 20035000
TI  - Sonographic changes after laparoscopic cystectomy compared with three-stage
      management in patients with ovarian endometriomas: a prospective randomized
      study.
AB  - BACKGROUND: Laparoscopic surgery is the gold standard treatment for ovarian
      endometriomas. The aim of this study was to evaluate the impact of two different
      laparoscopic methods on sonographic indicators of ovarian reserve in the treated
      ovary. METHODS: In this prospective randomized clinical trial, 20 patients with
      endometriomas were randomly assigned to undergo either laparoscopic cystectomy
      (Group 1) or the 'three-stage procedure' (Group 2). All patients underwent
      ultrasound examination preoperatively and 6 months after laparoscopy. Another
      ultrasound examination was performed 12 months after intervention in order to
      detect any recurrence. We investigated the alterations in the residual ovarian
      volume, ovarian vascular supply and antral follicle count (AFC) on the ovary with
      the endometriotic cyst by transvaginal color Doppler ultrasonography. RESULTS:
      The residual ovarian volume and the lowest pulsatility and resistance indexes
      were found to be similar between the two groups before and 6 months after
      laparoscopic intervention. The AFC of the operated ovary was increased
      significantly (P = 0.002) in Group 2 compared with Group 1 after 6 months. One
      year after laparoscopy, two recurrences of endometriomas were detected in Group
      2, although none were detected in Group 1 (P = 0.47). CONCLUSIONS: Ovarian
      volumes and vascularization were comparable among the two laparoscopic methods.
      On the contrary, functional ovarian tissue as determined by AFC was higher after
      the 'three-stage' procedure.

PMID- 20034998
TI  - Sensitivity of human visual and vestibular cortical regions to egomotion
      compatible visual stimulation.
AB  - The analysis and representation of visual cues to self-motion (egomotion) is
      primarily associated with cortical areas MST, VIP, and (recently) cingulate
      sulcus visual area (CSv). Various other areas, including visual areas V6 and V6A,
      and vestibular areas parietoinsular vestibular cortex (PIVC), putative area 2v
      (p2v), and 3aNv, are also potentially suited to processing egomotion (in some
      cases based on multisensory cues), but it is not known whether they are in fact
      involved in this process. In a functional magnetic resonance imaging (fMRI)
      experiment, we presented human participants with 2 types of random dot
      kinematograms. Both contained coherent motion but one simulated egomotion while
      the other did not. An area in the parieto-occipital sulcus that may correspond to
      V6, PIVC, and p2v were all differentially responsive to egomotion-compatible
      visual stimuli, suggesting that they may be involved in encoding egomotion. More
      generally, we show that the use of such stimuli provides a simple and reliable
      fMRI localizer for human PIVC and p2v, which hitherto required galvanic or
      caloric stimulation to be identified.

PMID- 20034999
TI  - The HIV-1 viral protein Tat increases glutamate and decreases GABA exocytosis
      from human and mouse neocortical nerve endings.
AB  - Human immunodeficiency virus-1 (HIV-1)-encoded transactivator of transcription
      (Tat) potentiated the depolarization-evoked exocytosis of [(3)H]D-aspartate
      ([(3)H]D-ASP) from human neocortical terminals. The metabotropic glutamate (mGlu)
      1 receptor antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl
      ester (CPCCOEt) prevented this effect, whereas the mGlu5 receptor antagonist 2
      methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) was ineffective. Western
      blot analysis showed that human neocortex synaptosomes possess mGlu1 and mGlu5
      receptors. Tat potentiated the K(+)-evoked release of [(3)H]D-ASP or of
      endogenous glutamate from mouse neocortical synaptosomes in a CPCCOEt-sensitive
      and MPEP-insensitive manner. Deletion of mGlu1 receptors (crv4/crv4 mice) or
      mGlu5 receptors (mGlu5(-/-)mouse) silenced Tat effects. Tat enhanced inositol
      1,4,5-trisphosphate production in human and mouse neocortical synaptosomes,
      consistent with the involvement of group I mGlu receptors. Tat inhibited the K(+)
      evoked release of [(3)H]gamma-aminobutyric acid ([(3)H]GABA) from human
      synaptosomes and that of endogenous GABA or [(3)H]GABA from mouse nerve
      terminals; the inhibition was insensitive to CPCCOEt or MPEP. Tat-induced effects
      were retained by Tat(37-72) but not by Tat(48-85). In mouse neocortical slices,
      Tat facilitated the K(+)- and the veratridine-induced release of [(3)H]D-ASP in a
      CPCCOEt-sensitive manner and was ineffective in crv4/crv4 mouse slices. These
      observations are relevant to the comprehension of the pathophysiological effects
      of Tat in central nervous system and may suggest new potential therapeutic
      approaches to the cure of HIV-1-associated dementia.

PMID- 20035001
TI  - Long-term respiratory symptoms in World Trade Center responders.
AB  - BACKGROUND: New York State (NYS) employees who responded to the World Trade
      Center (WTC) disaster on or after 11 September 2001 potentially experienced
      exposures that might have caused persistent respiratory effects. NYS responders
      represent a more moderately exposed population than typical first responders.
      AIMS: To assess whether NYS employees who were WTC responders were more likely
      than controls to report lower respiratory symptoms (LRS) or a diagnosis of asthma
      5 years post-9/11. Persistence and severity of symptoms were also evaluated.
      METHODS: Participants were initially mailed self-administered questionnaires
      (initial, Year 1, Year 2) and then completed a telephone interview in Year 3.
      Data were analysed using Poisson's regression models. RESULTS: WTC exposure was
      associated with LRS, including cough symptoms suggestive of chronic bronchitis, 5
      years post-9/11. When exposure was characterized using an exposure assessment
      method, the magnitude of effect was greater in those with exposure scores above
      the mean. WTC exposure was associated with persistence of LRS over the 3 year
      study period. Results also suggest that participants with the highest exposures
      were more likely to experience increased severity of their asthma condition
      and/or LRS. CONCLUSIONS: Our findings suggest that even in a moderately exposed
      responder population, lower respiratory effects were a persistent problem 5 years
      post-9/11, indicating that some WTC responders require ongoing monitoring.

PMID- 20035002
TI  - Compassion fatigue: experiences in occupational health, human resources,
      counselling and police.
AB  - BACKGROUND: This study examines the impact that working with distressed
      employees, clients and members of the public has on four caring professions:
      occupational health advisors (OHAs), human resource advisors (HRs), counsellors
      (CLs) and family liaison officers (FLOs). AIMS: To measure the levels of
      compassion fatigue in caring professions and to identify the mechanisms that lead
      to increased levels of personal growth. METHODS: Two hundred and seventy-six
      professionals (64 HRs, 53 OHAs, 114 CLs and 45 FLOs) completed the Carer Belief
      Inventory (CBI) (Tehrani, N. The cost of caring-the impact of secondary trauma on
      assumptions values and beliefs. Couns Psychol Q 2007;20:1-15.) and Short-Form of
      the Goldberg questionnaire (Goldberg D, Bridges K, Duncan-Jones P, Grayson D.
      Detecting anxiety and depression in a general medical setting. Br Med J
      1988;297:897-899). The participants in the study were attendees at presentations
      or training courses on employee wellbeing. Survey involved in the study also
      measured sources of support and coping mechanism. RESULTS: There were few
      differences in the level of negative beliefs between groups, although CLs were
      found to experience more feelings of isolation and FLOs and CLs were more likely
      to believe that there was no justice in the world. OHAs, CLs and FLOs were
      significantly more likely to demonstrate personal growth than HRs. Reflection on
      the work facilitated through professional or peer supervision and a healthy
      lifestyle was found to be associated with higher levels of personal growth and
      satisfaction with their performance at work. CONCLUSIONS: The results suggest
      that the provision of professional or peer supervision may be helpful in
      increasing reflection and 'sense making' leading to personal development and
      growth. Other forms of support that were found to be helpful included taking
      exercise, healthy eating and engaging in a hobby.

PMID- 20035003
TI  - Involvement of motility and flagella in Bacillus cereus biofilm formation.
AB  - Bacillus cereus is a food-borne pathogen and a frequent contaminant of food
      production plants. The persistence of this pathogen in various environments
      results from the formation of spores and of biofilms. To investigate the role of
      the B. cereus flagellar apparatus in biofilm formation, we constructed a non
      flagellated mutant and a flagellated but non-motile mutant. Unexpectedly, we
      found that the presence of flagella decreased the adhesion of the bacterium to
      glass surfaces. We hypothesize that this decrease is a consequence of the
      flagella hindering a direct interaction between the bacterial cell wall and the
      surface. In contrast, in specific conditions, motility promotes biofilm
      formation. Our results suggest that motility could influence biofilm formation by
      three mechanisms. Motility is necessary for the bacteria to reach surfaces
      suitable for biofilm formation. In static conditions, reaching the air-liquid
      interface, where the biofilm forms, is a strong requirement, whereas in flow
      cells bacteria can have access to the bottom glass slide by sedimentation.
      Therefore, motility is important for biofilm formation in glass tubes and in
      microtitre plates, but not in flow cells. Motility also promotes recruitment of
      planktonic cells within the biofilm by allowing motile bacteria to invade the
      whole biofilm. Finally, motility is involved in the spreading of the biofilm on
      glass surfaces.

PMID- 20035004
TI  - Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter
      jejuni reveals a number of genes with potential roles in invasion.
AB  - Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of
      Campylobacter jejuni, 01/51. A random transposon mutant library was screened in
      an in vitro assay of invasion and 26 mutants with a significant reduction in
      invasion were identified. Given that the invasion potential of C. jejuni is
      relatively poor compared to other enteric pathogens, the use of a hyper-invasive
      strain was advantageous as it greatly facilitated the identification of mutants
      with reduced invasion. The location of the transposon insertion in 23 of these
      mutants has been determined; all but three of the insertions are in genes also
      present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain
      transposon insertions in one region of the genome (approximately 14 kb), which
      when compared with the genome of NCTC 11168 overlaps with one of the previously
      reported plasticity regions and is likely to be involved in genomic variation
      between strains. Further characterization of one of the mutants within this
      region has identified a gene that might be involved in adhesion to host cells.

PMID- 20035005
TI  - Cloning and expression analysis of the duplicated genes for carbon monoxide
      dehydrogenase of Mycobacterium sp. strain JC1 DSM 3803.
AB  - Carbon monoxide dehydrogenase (CO-DH) is an enzyme catalysing the oxidation of CO
      to carbon dioxide in Mycobacterium sp. strain JC1 DSM 3803. Cloning of the genes
      encoding CO-DH from the bacterium and sequencing of overlapping clones revealed
      the presence of duplicated sets of genes for three subunits of the enzyme,
      cutB1C1A1 and cutB2C2A2, in operons, and a cluster of genes encoding proteins
      that may be involved in CO metabolism, including a possible transcriptional
      regulator. Phylogenetic analysis based on the amino acid sequences of large
      subunits of CO-DH suggested that the CO-DHs of Mycobacterium sp. JC1 and other
      mycobacteria are distinct from those of other types of bacteria. The growth
      phenotype of mutant strains lacking cutA genes and of a corresponding
      complemented strain showed that both of the duplicated sets of CO-DH genes were
      functional in this bacterium. Transcriptional fusions of the cutB genes with lacZ
      revealed that the cutBCA operons were expressed regardless of the presence of CO
      and were further inducible by CO. Primer extension analysis indicated two
      promoters, one expressed in the absence of CO and the other induced in the
      presence of CO. This is believed to be the first report to show the presence of
      multiple copies of CO-DH genes with identical sequences and in close proximity in
      carboxydobacteria, and to present the genetic evidence for the function of the
      genes in mycobacteria.

PMID- 20035006
TI  - Growth-related changes in intracellular spermidine and its effect on efflux pump
      expression and quorum sensing in Burkholderia pseudomallei.
AB  - The Burkholderia pseudomallei BpeAB-OprB resistance-nodulation-division (RND)
      family pump effluxes aminoglycoside and macrolide antibiotics as well as
      acylhomoserine lactones (AHLs) involved in quorum sensing. Expression of bpeA
      lacZ was cell density-dependent and was inducible in the presence of these
      compounds. Intracellular levels of spermidine and N-acetylspermidine increased
      with cell density in wild-type B. pseudomallei KHW, but were always lower in the
      bpeAB pump mutant at all growth phases. The significance of changes in
      intracellular spermidine on efflux pump expression was demonstrated by the
      disruption of the binding of the BpeR repressor protein to the bpeABoprB
      regulatory region in vitro in the presence of increasing spermidine
      concentrations. This was supported by dose-dependent activation of bpeA-lacZ
      transcription in vivo in the presence of exogenous spermidine and N
      acetylspermidine, thus implicating the involvement of the BpeAB-OprB pump in
      spermidine homeostasis in B. pseudomallei. Consequently, inhibition of
      intracellular spermidine synthesis reduced the efflux of AHLs by BpeAB-OprB.
      Other potential therapeutic applications of spermidine synthase inhibitors
      include the reduction of swimming motility and biofilm formation by B.
      pseudomallei.

PMID- 20035007
TI  - Differentiation of Mycoplasma gallisepticum strains using PCR and high-resolution
      melting curve analysis.
AB  - Mycoplasma gallisepticum (MG) is an economically important pathogen of poultry
      worldwide, causing chronic respiratory disease in chickens and turkeys.
      Differentiation of MG strains is critical, especially in countries where poultry
      flocks are vaccinated with live vaccines. In this study, oligonucleotide primers
      were designed based on a region preceding the trinucleotide repeat of a member of
      the vlhA gene family, and amplicons of 145-352 bp were generated from cultures of
      10 different MG strains, including the ts-11, F and 6/85 vaccine strains. High
      resolution melting (HRM) curve analysis of the resultant amplicons could
      differentiate all MG strains. Analysis of the nucleotide sequences of the
      amplicons from each strain revealed that each melting curve profile related to a
      unique DNA sequence. The HRM curve profiles (for ts-11) remained consistent after
      at least five passages under laboratory conditions. PCR-HRM curve analysis of 33
      DNA extracts derived from respiratory swabs, or mycoplasma cultures grown from
      respiratory swabs, of ts-11-vaccinated commercial or specific pathogen-free
      chickens identified all these specimens, according to their sequences, as ts-11.
      The potential of the PCR-HRM curve analysis was also shown in the genotyping of
      30 additional MG isolates from Europe, the USA and Israel. The results presented
      in this study indicate that PCR followed by HRM curve analysis provides a rapid
      and robust technique for genotyping of MG isolates/strains using both MG cultures
      and clinical swabs.

PMID- 20035008
TI  - Induction of Salmonella pathogenicity island 1 under different growth conditions
      can affect Salmonella-host cell interactions in vitro.
AB  - Salmonella invade non-phagocytic cells by inducing massive actin rearrangements,
      resulting in membrane ruffle formation and phagocytosis of the bacteria. This
      process is mediated by a cohort of effector proteins translocated into the host
      cell by type III secretion system 1, which is encoded by genes in the Salmonella
      pathogenicity island (SPI) 1 regulon. This network is precisely regulated and
      must be induced outside of host cells. In vitro invasive Salmonella are prepared
      by growth in synthetic media although the details vary. Here, we show that
      culture conditions affect the frequency, and therefore invasion efficiency, of
      SPI1-induced bacteria and also can affect the ability of Salmonella to adapt to
      its intracellular niche following invasion. Aerobically grown late-exponential
      phase bacteria were more invasive and this was associated with a greater
      frequency of SPI1-induced, motile bacteria, as revealed by single-cell analysis
      of gene expression. Culture conditions also affected the ability of Salmonella to
      adapt to the intracellular environment, since they caused marked differences in
      intracellular replication. These findings show that induction of SPI1 under
      different pre-invasion growth conditions can affect the ability of Salmonella to
      interact with eukaryotic host cells.

PMID- 20035009
TI  - Dissecting interactions between nucleosides and germination receptors in Bacillus
      cereus 569 spores.
AB  - Bacillus cereus 569 spores germinate either with inosine as a sole germinant or
      with a combination of nucleosides and L-alanine. Whereas the inosine-only
      germination pathway requires the presence of two different germination receptors
      (GerI and GerQ) to be activated, the nucleoside/alanine germination pathway only
      needs one of the two receptors. To differentiate how nucleoside recognition
      varies between the inosine-only germination pathway and the nucleoside/alanine
      germination pathway, we tested 61 purine analogues as agonists and antagonists of
      the two pathways in wild-type, DeltagerI and DeltagerQ spores. The structure
      activity relationships of germination agonists and antagonists suggest that the
      inosine-only germination pathway is restricted to recognize a single germinant
      (inosine), but can be inhibited in predictable patterns by structurally distinct
      purine nucleosides. B. cereus spores encoding GerI as the only nucleoside
      receptor (DeltagerQ mutant) showed a germination inhibition profile similar to
      wild-type spores treated with inosine only. Thus, GerI seems to have a well
      organized binding site that recognizes inosine and inhibitors through specific
      substrate-protein interactions. Structure-activity analysis also showed that the
      nucleoside/alanine germination pathway is more promiscuous toward purine
      nucleoside agonists, and is only inhibited by hydrophobic analogues. B. cereus
      spores encoding GerQ as the only nucleoside receptor (DeltagerI mutant) behaved
      like wild-type spores treated with inosine and L-alanine. Thus, the GerQ receptor
      seems to recognize substrates in a more flexible binding site through non
      specific interactions. We propose that the GerI receptor is responsible for
      germinant detection in the inosine-only germination pathway. On the other hand,
      supplementing inosine with l-alanine allows bypassing of the GerI receptor to
      activate the more flexible GerQ receptor.

PMID- 20035010
TI  - Psychosocial risk factors and retinal microvascular signs: the multi-ethnic study
      of atherosclerosis.
AB  - The association between psychosocial risk factors and retinal microvascular signs
      was examined in the Multi-Ethnic Study of Atherosclerosis. Subjects were
      recruited from Baltimore, Maryland; Chicago, Illinois; Forsyth County, North
      Carolina; Los Angeles County, California; New York, New York; and St. Paul,
      Minnesota. Levels of depressive symptoms, trait anger, trait anxiety, chronic
      burdens, emotional support, and cynical distrust were assessed by questionnaire
      (from July 2000 to July 2002). Digital retinal images (from August 2002 to
      January 2004) from 6,147 participants were used to evaluate retinopathy and
      retinal vascular caliber. After controlling for potential confounding factors,
      the authors found that subjects without access to emotional support (Enriched
      Social Support Instrument score of <19 vs. > or = 19) had 60% greater odds of
      retinopathy (odds ratio = 1.6, 95% confidence interval (CI): 1.3, 2.0). Subjects
      with high Spielberger trait-anxiety scale scores (> or = 22 vs. < or = 14) and
      subjects with high depressive symptoms (Center for Epidemiology Studies
      Depression Scale score, > or = 16 vs. <16) were also more likely to have
      retinopathy (odds ratio = 1.4, 95% CI: 1.1, 1.9 and odds ratio = 1.5, 95% CI:
      1.2, 1.9), respectively. In this cross-sectional study, lack of emotional
      support, increased trait anxiety, and more depressive symptoms were associated
      with retinopathy signs, independently of other known risk factors.

PMID- 20035011
TI  - Effects of externally rated job demand and control on depression diagnosis claims
      in an industrial cohort.
AB  - This study examined whether externally rated job demand and control were
      associated with depression diagnosis claims in a heavy industrial cohort. The
      retrospective cohort sample consisted of 7,566 hourly workers aged 18-64 years
      who were actively employed at 11 US plants between January 1, 1996, and December
      31, 2003, and free of depression diagnosis claims during an initial 2-year run-in
      period. Logistic regression analysis was used to model the effect of tertiles of
      demand and control exposure on depression diagnosis claims. Demand had a
      significant positive association with depression diagnosis claims in bivariate
      models and models adjusted for demographic (age, gender, race, education, job
      grade, tenure) and lifestyle (smoking status, body mass index, cholesterol level)
      variables (high demand odds ratio = 1.39, 95% confidence interval: 1.04, 1.86).
      Control was associated with greater risk of depression diagnosis at moderate
      levels in unadjusted models only (odds ratio = 1.47, 95% confidence interval:
      1.12, 1.93), while low control, contrary to expectation, was not associated with
      depression. The effects of the externally rated demand exposure were lost with
      adjustment for location. This may reflect differences in measurement or
      classification of exposure, differences in depression diagnosis by location, or
      other location-specific factors.

PMID- 20035012
TI  - Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting
      and transactivation.
AB  - Runx1 is a key hematopoietic transcription factor required for definitive
      hematopoiesis and is a frequent target of leukemia-related chromosomal
      translocations. The resulting fusion proteins, while retaining DNA binding
      activity, display loss of subnuclear targeting and associated transactivation
      functions encoded by the C-terminus of the protein. To define the precise
      contribution of the Runx1 C-terminus in development and leukemia, we created a
      knock-in mouse with a C-terminal truncation by introducing a single nucleic acid
      substitution in the native Runx1 locus. This mutation (Runx1(Q307X)) models
      genetic lesions observed in patients with leukemia and myeloproliferative
      disorders. The Runx1(Q307X) homozygous mouse exhibits embryonic lethality at
      E12.5 due to central nervous system hemorrhages and a complete lack of
      hematopoietic stem cell function. While able to bind DNA, Runx1(Q307X) is unable
      to activate target genes, resulting in deregulation of various hematopoietic
      markers. Thus, we demonstrate that the subnuclear targeting and transcriptional
      regulatory activities of the Runx1 C-terminus are critical for hematopoietic
      development. We propose that compromising the C-terminal functions of Runx1 is a
      common mechanism for the pathological consequences of a variety of somatic
      mutations and Runx1-related leukemic fusion proteins observed in human patients.

PMID- 20035013
TI  - Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA
      biogenesis.
AB  - The nuclear poly(A)-binding protein 1 (PABPN1) is a ubiquitously expressed
      protein that plays a critical role in polyadenylation. Short expansions of the
      polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular
      dystrophy (OPMD), which is an adult onset disease characterized by eyelid
      drooping, difficulty in swallowing and weakness in the proximal limb muscles.
      Although significant data from in vitro biochemical assays define the function of
      PABPN1 in control of poly(A) tail length, little is known about the role of
      PABPN1 in mammalian cells. To assess the function of PABPN1 in mammalian cells
      and specifically in cells affected in OPMD, we examined the effects of PABPN1
      depletion using siRNA in primary mouse myoblasts from extraocular, pharyngeal and
      limb muscles. PABPN1 knockdown significantly decreased cell proliferation and
      myoblast differentiation during myogenesis in vitro. At the molecular level,
      PABPN1 depletion in myoblasts led to a shortening of mRNA poly(A) tails,
      demonstrating the cellular function of PABPN1 in polyadenylation control in a
      mammalian cell. In addition, PABPN1 depletion caused nuclear accumulation of
      poly(A) RNA, revealing that PABPN1 is required for proper poly(A) RNA export from
      the nucleus. Together, these experiments demonstrate that PABPN1 plays an
      essential role in myoblast proliferation and differentiation, suggesting that it
      is required for muscle regeneration and maintenance in vivo.

PMID- 20035014
TI  - Deficits in sensory-specific devaluation task performance following genetic
      deletions of cannabinoid (CB1) receptor.
AB  - Cannabinoid CB1 receptor is abundantly expressed throughout the CNS and is
      implicated in numerous physiological and behavioral functions, including appetite
      and feeding. In the present study, wild-type and CB1 heterozygous and homozygous
      knockout mice were tested on an instrumental outcome-selective devaluation task
      to assess changes in acquired instrumental response levels for a distinct food
      reward following selective satiation. Deletion of CB1 receptor, as well as
      reduction in CB1 expression (HET), produced deficits in outcome-selective
      instrumental devaluation. These results identify a critical role for CB1 receptor
      in the ability of animals to represent, update, and/or use sensory-specific
      outcome representations to alter appetitive behaviors.

PMID- 20035015
TI  - Long-term synaptic changes in two input pathways into the lateral nucleus of the
      amygdala underlie fear extinction.
AB  - Plasticity in two input pathways into the lateral nucleus of the amygdala (LA),
      the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested
      to underlie extinction, suppression of a previously acquired conditioned response
      (CR) following repeated presentations of the conditioned stimulus (CS). However,
      little is known about the joint dynamics of the relevant synaptic changes within
      the LA that accompany fear extinction. Employing a novel training procedure, in
      which stimulation of the medial geniculate nucleus (MGm) of the thalamus served
      as the CS, we tested necessary and sufficient conditions for extinction in
      anesthetized rats. Repeatedly applying the brain-stimulation CS was neither
      sufficient to produce activation of the mPFC nor behavioral extinction when the
      animal was under anesthesia. Only when the CS was combined with contingent
      stimulation of the infralimbic cortex (IL) of the mPFC was the CR markedly
      reduced, emulating extinction. To elucidate the nature of synaptic alterations
      linking the extinction procedure with CR suppression, evoked field potentials to
      IL and MGm stimulations were recorded in the LA. The results showed that paired
      stimulations of the IL and MGm significantly enhanced the neural response at the
      IL-LA synapses and reversed conditioning-induced synaptic potentiation at the MGm
      LA synapses. Taken together, our results provide strong evidence that dual
      plasticity within the LA underlies suppression of conditioned fear response
      following extinction.

PMID- 20035017
TI  - Type I and Type II error concerns in fMRI research: re-balancing the scale.
AB  - Statistical thresholding (i.e. P-values) in fMRI research has become increasingly
      conservative over the past decade in an attempt to diminish Type I errors (i.e.
      false alarms) to a level traditionally allowed in behavioral science research. In
      this article, we examine the unintended negative consequences of this single
      minded devotion to Type I errors: increased Type II errors (i.e. missing true
      effects), a bias toward studying large rather than small effects, a bias toward
      observing sensory and motor processes rather than complex cognitive and affective
      processes and deficient meta-analyses. Power analyses indicate that the
      reductions in acceptable P-values over time are producing dramatic increases in
      the Type II error rate. Moreover, the push for a mapwide false discovery rate
      (FDR) of 0.05 is based on the assumption that this is the FDR in most behavioral
      research; however, this is an inaccurate assessment of the conventions in actual
      behavioral research. We report simulations demonstrating that combined intensity
      and cluster size thresholds such as P < 0.005 with a 10 voxel extent produce a
      desirable balance between Types I and II error rates. This joint threshold
      produces high but acceptable Type II error rates and produces a FDR that is
      comparable to the effective FDR in typical behavioral science articles (while a
      20 voxel extent threshold produces an actual FDR of 0.05 with relatively common
      imaging parameters). We recommend a greater focus on replication and meta
      analysis rather than emphasizing single studies as the unit of analysis for
      establishing scientific truth. From this perspective, Type I errors are self
      erasing because they will not replicate, thus allowing for more lenient
      thresholding to avoid Type II errors.

PMID- 20035016
TI  - Neural correlates of incidental and directed facial emotion processing in
      adolescents and adults.
AB  - Our knowledge on the development of the affective and cognitive circuitries that
      underlie affect regulation is still limited. This functional magnetic resonance
      imaging (fMRI) study examined whether there is more efficient prefrontal
      modulation of affective circuits with development. Ten adolescents (mean age 14
      +/- 2 years) and 10 adults (mean age 30 +/- 6 years) underwent two scanning
      conditions that required different levels of cognitive control over face emotion
      processing. A 'directed' emotion processing condition required judgment of facial
      expressions. An 'incidental' emotion processing condition required an age
      judgment. For the incidental emotion processing condition, adolescents, compared
      with adults, showed less activation in right ventrolateral prefrontal cortex
      (VLPFC) and greater activation in paralimbic regions, suggesting greater
      emotional reactivity and immature prefrontal circuitries for affect regulation.
      For the directed emotion processing condition, adolescents, compared with adults,
      showed decreased recruitment of both the dorsal and pregenual right anterior
      cingulate cortex (ACC), suggesting immature modulatory functions of the ACC
      during directed face emotion processing. These results indicate that the neural
      circuitries for affect regulation are still developing in adolescence and have
      not yet reached the adult level.

PMID- 20035019
TI  - Decline of EMRSA-16 amongst methicillin-resistant Staphylococcus aureus causing
      bacteraemias in the UK between 2001 and 2007.
AB  - OBJECTIVES: Between 1998 and 2000, 95.6% of methicillin-resistant Staphylococcus
      aureus (MRSA) bacteraemias in the UK were due to two epidemic strains, namely
      EMRSA-15 or EMRSA-16 (60.2% and 35.4%, respectively). We sought to determine the
      proportions of these strains before and after the general decline in MRSA
      bacteraemia that began around 2004. METHODS: Consecutive MRSA isolates collected
      in 2001, 2003, 2005 and 2007 by the BSAC Bacteraemia Surveillance Programme were
      categorized to multilocus sequence typing (MLST) clonal complex and to SCCmec
      type by PCR. MICs were determined by the BSAC method. Data trends were tested for
      significance using a generalized linear regression model. RESULTS: Collectively,
      EMRSA-15 and EMRSA-16 consistently accounted for approximately 95% of MRSA
      studied between 2001 and 2007, but the proportions of EMRSA-16 declined from
      21.4% in 2001 to 9% in 2007 (P < 0.05), whilst the proportion of EMRSA-15 rose
      commensurately, accounting for 85% of MRSA in 2007. Ciprofloxacin and
      erythromycin resistance were common amongst both EMRSA-15 and EMRSA-16.
      CONCLUSIONS: EMRSA-15 and EMRSA-16 remain the main MRSA strains in bacteraemia in
      the UK, but the proportion of EMRSA-16 declined from the late 1990 s, thus
      preceding the general decline in MRSA bacteraemias that began in the middle of
      the present decade.

PMID- 20035018
TI  - An fMRI investigation of the cultural specificity of music memory.
AB  - This study explored the role of culture in shaping music perception and memory.
      We tested the hypothesis that listeners demonstrate different patterns of
      activation associated with music processing-particularly right frontal cortex
      when encoding and retrieving culturally familiar and unfamiliar stimuli, with the
      latter evoking broader activation consistent with more complex memory tasks.
      Subjects (n = 16) were right-handed adults born and raised in the USA (n = 8) or
      Turkey (n = 8) with minimal music training. Using fMRI procedures, we scanned
      subjects during two tasks: (i) listening to novel musical examples from their own
      culture and an unfamiliar culture and (ii) identifying which among a series of
      brief excerpts were taken from the longer examples. Both groups were more
      successful remembering music of their home culture. We found greater activation
      for culturally unfamiliar music listening in the left cerebellar region, right
      angular gyrus, posterior precuneus and right middle frontal area extending into
      the inferior frontal cortex. Subjects demonstrated greater activation in the
      cingulate gyrus and right lingual gyrus when engaged in recall of culturally
      unfamiliar music. This study provides evidence for the influence of culture on
      music perception and memory performance at both a behavioral and neurological
      level.

PMID- 20035020
TI  - Tetracycline resistance in Chilean clinical isolates of Helicobacter pylori.
AB  - OBJECTIVES: Since high-level tetracycline resistance in Helicobacter pylori has
      been associated with a AGA926-928-->TTC substitution in the 16S rRNA genes
      rrnA/B, the aim of the study was to screen for tetracycline resistance in H.
      pylori clinical isolates obtained from Santiago, Chile by using a recently
      reported molecular assay. METHODS: A PCR-restriction fragment length polymorphism
      (PCR-RFLP) assay of the conserved 535 bp region of the H. pylori 16S rRNA genes
      rrnA/B (between nucleotides 710 and 1245) using HinfI was followed by DNA
      sequencing of the same fragment obtained from tetracycline-resistant H. pylori
      clinical isolates. RESULTS: The PCR-RFLP assay revealed that the tetracycline
      resistant H. pylori isolates lacked the AGA926-928-->TTC substitution. In
      contrast, DNA sequencing of the 535 bp PCR fragment from 11 tetracycline
      resistant H. pylori Chilean clinical isolates showed an association of low-level
      tetracycline resistance with 1 bp (A928C) or 2 bp (AG926-927-->GT and/or
      A926G/A928C) substitutions in both 16S rRNA genes. CONCLUSIONS: The PCR-RFLP
      (HinfI) assay alone is unreliable for the detection of tetracycline resistance in
      Chilean clinical isolates of H. pylori. To that end, it must be complemented by
      sequencing of the 535 bp PCR fragment.

PMID- 20035021
TI  - Safety of triazole antifungal drugs in patients with cancer.
AB  - Triazole drugs are widely used in cancer patients for prophylaxis and treatment
      of life-threatening invasive fungal infections. Fluconazole, available for over
      two decades, is safe and effective in patients with cancer; however, the
      excellent safety profile of fluconazole may not be applicable to the newer
      triazoles. Itraconazole, voriconazole and posaconazole are associated with
      adverse events, and drug interactions frequently occur, particularly in cancer
      patients, since the triazoles and many drugs used in cancer chemotherapy are
      metabolized via a common metabolic pathway, the hepatic cytochrome P450 system.
      Close monitoring for drug interactions is needed when triazoles are used with
      anti-neoplastic drugs and dosage modification of the triazole or its
      discontinuation may be required. Monitoring of triazole serum concentrations is
      becoming an important aspect of management to minimize toxicity and ensure
      efficacy.

PMID- 20035022
TI  - The constitutive activity of the human muscarinic M3 receptor unmasks differences
      in the pharmacology of anticholinergics.
AB  - An activator protein 1-driven luciferase reporter assay was developed to monitor
      the activation of the human muscarinic M3 receptor (hM3-R) and evaluate
      functional potencies of different anticholinergics in Chinese hamster ovary
      cells. This assay proved to be superior to previously used functional assays
      [i.e., inositol phosphate accumulation (J Pharmacol Exp Ther 330:660-668, 2009)],
      thanks to the longer incubation times that allow reaching of pseudoequilibrium
      for ligands with slower dissociation kinetics, the long-acting muscarinic
      antagonists. Interestingly, within this system the hM3-R efficiently signaled in
      an agonist-independent manner. All the antagonists tested were able to inhibit
      the hM3-R constitutive activity in a concentration-dependent fashion, behaving as
      full inverse agonists. Curiously, significant differences in potency as
      antagonists (against carbachol) and inverse agonists were seen for some compounds
      (N-methyl scopolamine and tiotropium). Given the potential for inverse agonists
      to cause receptor up-regulation, the effect of chronic exposure to
      anticholinergics on the expression levels of hM3-R was also tested. Again,
      significant differences were seen, with some ligands (e.g., tiotropium) producing
      less than half of the receptor up-regulation caused by other anticholinergics.
      This study shows that anticholinergics can exhibit differential behaviors, which
      depend on the pathway investigated, and therefore provides evidence that the
      molecular mechanism of inverse agonism is likely to be more complex than the
      stabilization of a single inactive receptor conformation. In addition,
      differences in the potential of anticholinergics to induce hM3-R up-regulation
      might have clinical relevance, because many are on the market or in clinical
      trials as chronic treatment for chronic obstructive pulmonary disease, for
      example.

PMID- 20035023
TI  - Xenobiotic-metabolizing cytochromes p450 in human white adipose tissue:
      expression and induction.
AB  - Lipophilic pollutants can accumulate in human white adipose tissue (WAT), and the
      consequences of this accumulation are still poorly understood. Cytochromes P450
      (P450s) have recently been found in rat WAT and shown to be inducible through
      mechanisms similar to those in the liver. The aim of our study was to describe
      the cytochrome P450 pattern and their induction mechanisms in human WAT. Explants
      of subcutaneous and visceral WAT and primary culture of subcutaneous adipocytes
      were used as WAT models, and liver biopsies and primary culture of hepatocytes
      were used as liver models to characterize P450 expression in both tissues. The
      WAT and liver models were then treated with typical P450 inducers (rifampicin,
      phenobarbital, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) and lipophilic pollutants
      (lindane, prochloraz, and chlorpyrifos), and the effects on P450 expression were
      studied. P450 expression was considerably lower in WAT than in the liver, except
      for CYP1B1 and CYP2U1, which were the most highly expressed adipose P450s in all
      individuals. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and prochloraz induced CYP1A1
      and CYP1B1 expression in both tissues. The aryl hydrocarbon receptor was also
      present in WAT. In contrast, neither phenobarbital nor rifampicin treatment
      induced CYP2 or CYP3 mRNA in WAT, and constitutive androstane receptor and
      pregnane X receptor were almost undetectable. These results suggest that the
      mechanisms by which P450s of family 1 are regulated in the liver are also
      functional in human WAT, but those regulating CYP2 and CYP3 expression are not.

PMID- 20035024
TI  - Direct 16S rRNA gene sequencing of polymicrobial culture-negative samples with
      analysis of mixed chromatograms.
AB  - Two cases involving polymicrobial culture-negative samples were investigated by
      16S rRNA gene sequencing, with analysis of mixed chromatograms. Fusobacterium
      necrophorum, Prevotella intermedia and Streptococcus constellatus were identified
      from pleural fluid in a patient with Lemierre's syndrome and Neisseria
      meningitidis and Escherichia coli were identified from a petechia in a patient
      with meningococcal disease.

PMID- 20035025
TI  - Dynamics of extracellular release of Aspergillus fumigatus DNA and galactomannan
      during growth in blood and serum.
AB  - Aspergillus fumigatus is the major cause of invasive aspergillosis (IA), a
      disease associated with high rates of morbidity and mortality in patients
      undergoing treatment for haematological malignancies. This study investigated A.
      fumigatus growth in vitro and in a murine model of IA in order to provide
      insights into the dynamics of extracellular DNA and galactomannan (GM) release
      and their relevance to early diagnosis of IA. Following inoculation of whole
      blood with 20 A. fumigatus conidia ml(-1), DNA that corresponded to the inoculum
      could be detected by PCR but GM was not detected in plasma separated from the
      blood sample, indicating that the fungus did not grow in whole blood. The
      quantities of DNA detected by PCR, and GM, were proportional to the amount of
      fungal biomass present in vitro. Fungal DNA could be detected in the sera of mice
      experimentally infected with A. fumigatus with maximum detection in
      cyclophosphamide-treated mice.

PMID- 20035026
TI  - Gap junction heterogeneity as mechanism for electrophysiologically distinct
      properties across the ventricular wall.
AB  - Gap junctions are critical to maintaining synchronized impulse propagation and
      repolarization. Heterogeneous expression of the principal ventricular gap
      junction protein connexin43 (Cx43) is associated with action potential duration
      (APD) dispersion across the anterior ventricular wall. Little is known about Cx43
      expression patterns and their disparate impact on regional electrophysiology
      throughout the heart. We aimed to determine whether the anterior and posterior
      regions of the heart are electrophysiologically distinct. Multisegment, high
      resolution optical mapping was performed in canine wedge preparations harvested
      separately from the anterior left ventricle (aLV; n = 8) and posterior left
      ventricle (pLV; n = 8). Transmural APD dispersion was significantly greater on
      the aLV than the pLV (45 +/- 13 vs. 26 +/- 8.0 ms; P < 0.05). Conduction velocity
      dispersion was also significantly higher (P < 0.05) across the aLV (39 +/- 7%)
      than the pLV (16 +/- 3%). Carbenoxolone perfusion significantly enhanced APD and
      conduction velocity dispersion on the aLV (by 1.53-fold and 1.36-fold,
      respectively), but not the pLV (by 1.27-fold and 1.2-fold, respectively), and
      produced a 4.2-fold increase in susceptibility to inducible arrhythmias in the
      aLV. Confocal immunofluorescence microscopy revealed significantly (P < 0.05)
      greater transmural dispersion of Cx43 expression on the aLV (44 +/- 10%) compared
      with the pLV wall (8.3 +/- 0.7%), suggesting that regional expression of Cx43
      expression patterns may account for regional electrophysiological differences.
      Computer simulations affirmed that localized uncoupling at the epicardial
      midmyocardial interface is sufficient to produce APD gradients observed on the
      aLV. These data demonstrate that the aLV and pLV differ importantly with respect
      to their electrophysiological properties and Cx43 expression patterns.
      Furthermore, local underexpression of Cx43 is closely associated with transmural
      electrophysiological heterogeneity on the aLV. Therefore, regional and transmural
      heterogeneous Cx43 expression patterns may be an important mechanism underlying
      arrhythmia susceptibility, particularly in disease states where gap junction
      expression is altered.

PMID- 20035027
TI  - Equilibrative nucleoside transporter 1 plays an essential role in
      cardioprotection.
AB  - To better understand the role of equilibrative nucleoside transporters (ENT) in
      purine nucleoside-dependent physiology of the cardiovascular system, we
      investigated whether the ENT1-null mouse heart was cardioprotected in response to
      ischemia (coronary occlusion for 30 min followed by reperfusion for 2 h). We
      observed that ENT1-null mouse hearts showed significantly less myocardial
      infarction compared with wild-type littermates. We confirmed that isolated wild
      type adult mouse cardiomyocytes express predominantly ENT1, which is primarily
      responsible for purine nucleoside uptake in these cells. However, ENT1-null
      cardiomyocytes exhibit severely impaired nucleoside transport and lack ENT1
      transcript and protein expression. Adenosine receptor expression profiles and
      expression levels of ENT2, ENT3, and ENT4 were similar in cardiomyocytes isolated
      from ENT1-null adult mice compared with cardiomyocytes isolated from wild-type
      littermates. Moreover, small interfering RNA knockdown of ENT1 in the
      cardiomyocyte cell line, HL-1, mimics findings in ENT1-null cardiomyocytes. Taken
      together, our data demonstrate that ENT1 plays an essential role in
      cardioprotection, most likely due to its effects in modulating purine nucleoside
      dependent signaling and that the ENT1-null mouse is a powerful model system for
      the study of the role of ENTs in the physiology of the cardiomyocyte.

PMID- 20035028
TI  - Soluble epoxide hydrolase inhibition modulates vascular remodeling.
AB  - The soluble epoxide hydrolase enzyme (SEH) and vascular remodeling are associated
      with cardiovascular disease. Although inhibition of SEH prevents smooth muscle
      cell proliferation in vitro, the effects of SEH inhibition on vascular remodeling
      in vivo and mechanisms of these effects remain unclear. Herein we determined the
      effects of SEH antagonism in an endothelium intact model of vascular remodeling
      induced by flow reduction and an endothelium denuded model of vascular injury. We
      demonstrated that chronic treatment of spontaneously hypertensive stroke-prone
      rats with 12-(3-adamantan-1-yl-ureido) dodecanoic acid, an inhibitor of SEH,
      improved the increment of inward remodeling induced by common carotid ligation to
      a level that was comparable with normotensive Wistar Kyoto rats. Similarly, mice
      with deletion of the gene responsible for the production of the SEH enzyme
      (Ephx2(-/-)) demonstrated enhanced inward vascular remodeling induced by carotid
      ligation. However, the hyperplastic response induced by vascular injury that
      denudes the endothelium was unabated by SEH inhibition or Ephx2 gene deletion.
      These results suggest that SEH inhibition or Ephx2 gene deletion antagonizes
      neointimal formation in vivo by mechanisms that are endothelium dependent. Thus
      SEH inhibition may have therapeutic potential for flow-induced remodeling and
      neointimal formation.

PMID- 20035029
TI  - Biaxial mechanical properties of intact and layer-dissected human carotid
      arteries at physiological and supraphysiological loadings.
AB  - Specimens of intact wall tubes of human common carotid arteries (CCA), internal
      carotid arteries (ICA) (n = 11, age 77.6 yr, SD 6.3), and related adventitia and
      media-intima tubes are mechanically examined. Cyclic, quasi-static extension
      inflation tests at different axial stretches are performed on preconditioned tube
      specimens. Stress-free configurations show significant stress releases in the
      circumferential direction of the intact CCA and ICA walls and in the axial
      directions of the intact CCA walls and the CCA and ICA adventitias. All
      investigated tissues exhibit strong nonlinear, pseudoelastic mechanical behavior
      with small hysteresis. The "inversion" feature, where the pressure/axial stretch
      relationship becomes a vertical line, is found only for intact walls. Axial
      "inversion stretches" are 1.15 (SD 0.06) for CCA and 1.14 (SD 0.06) for ICA, and
      related external axial forces are 0.43 N (SD 0.15) and 0.30 N (SD 0.22),
      respectively. Significant negative correlations between age and axial inversion
      stretches for CCA (r = -0.67, P = 0.03) and ICA (r = -0.29, P = 0.04) are
      identified. Adventitias are very compliant at low pressures, but change into
      stiff tubes at high pressures. The burst pressure of the adventitia is beyond 250
      kPa. A relatively low burst pressure of approximately 60 kPa is found in the
      media-intima tubes, in which the pressure/circumferential stretch relationships
      are almost independent of the axial stretches. Stress analyses indicate a high
      degree of material anisotropy for all investigated tissues. High circumferential
      and axial stresses occur in the media-intima tubes at physiological conditions.
      The obtained data are intended to serve for an improvement of constitutive laws,
      determination of constitutive parameters, and enhancing our knowledge of the
      mechanical functions of arteries and their associated layers in specific
      pathophysiological and clinical problems, such as hypertension and angioplasty
      with stenting.

PMID- 20035030
TI  - Heart failure switches the RV alpha1-adrenergic inotropic response from negative
      to positive.
AB  - Right ventricular (RV) failure is a serious common clinical problem that is
      poorly understood. Therefore, for failing and nonfailing hearts, we examined the
      distinctive inotropic responses induced in the RV myocardium after the
      stimulation of alpha(1)-adrenergic receptors (ARs). In RV trabeculae from
      nonfailing mouse hearts, alpha(1)-ARs induced a negative inotropic response,
      consistent with our previous study. In marked contrast, in RV trabeculae from
      failing hearts, 12 wk after coronary artery ligation, alpha(1)-ARs induced a
      positive inotropic response. Mechanistically, experiments with skinned trabeculae
      showed that alpha(1)-ARs decreased myofilament Ca(2+) sensitivity in the
      nonfailing RV myocardium, whereas alpha(1)-ARs increased Ca(2+) sensitivity in
      heart failure. This suggests that a switch in the Ca(2+) sensitivity response to
      alpha(1)-AR stimulation explained the switch in the RV alpha(1)-AR inotropic
      response in heart failure. Myosin light chain kinase (MLCK) can increase
      myofilament Ca(2+) sensitivity, and the smooth muscle isoform (smMLCK), which is
      also present in cardiomyocytes, was more abundant in the RV myocardium from
      failing versus nonfailing hearts. Moreover, the MLCK inhibitor ML-9 prevented the
      switch of the RV myocardium to a positive alpha(1)-AR inotropic response in heart
      failure. In the left ventricular myocardium, in contrast, alpha(1)-AR inotropic
      responses were not different in failing versus nonfailing hearts, and smMLCK
      abundance was not increased in heart failure. In relation to human disease, we
      found that smMLCK mRNA and protein levels were increased in RVs from failing
      human hearts. We conclude that the RV inotropic response to alpha(1)-ARs is
      switched from negative to positive in heart failure, through a pathway involving
      increased myofilament Ca(2+) sensitivity. Since alpha(1)-AR agonist
      catecholamines are elevated in heart failure, increased alpha(1)-AR inotropic
      responses in the RV myocardium may be adaptive in heart failure by helping the
      failing RV respond to increased pulmonary pressures.

PMID- 20035031
TI  - Both beta1- and beta2-adrenoceptors contribute to feedforward coronary resistance
      vessel dilation during exercise.
AB  - During exercise, beta-feedforward coronary vasodilation has been shown to
      contribute to the matching of myocardial oxygen supply with the demand of the
      myocardium. Since both beta(1)- and beta(2)-adrenoceptors are present in the
      coronary microvasculature, we investigated the relative contribution of these
      subtypes to beta-feedforward coronary vasodilation during exercise as well as to
      infusion of the beta(1)-agonist norepinephrine and the beta(1)- and beta(2)
      agonist isoproterenol. Chronically instrumented swine were studied at rest and
      during graded treadmill exercise (1-5 km/h) under control conditions and after
      beta(1)-blockade with metoprolol (0.5 mg/kg iv) and beta(1)/beta(2)-blockade with
      propranolol (0.5 mg/kg iv). The selectivity and degree of beta-blockade of
      metoprolol and propranolol were confirmed using isoproterenol infusion (0.05-0.4
      microg. kg(-1).min(-1)) under resting conditions. Isoproterenol-induced coronary
      vasodilation was mediated through the beta(2)-adrenoceptor, whereas
      norepinephrine-induced coronary vasodilation was principally mediated through the
      beta(1)-adrenoceptor. Exercise resulted in a significant increase in left
      ventricular norepinephrine release and epinephrine uptake. beta(1)-Adrenoceptor
      blockade with metoprolol had very little effect under resting conditions.
      However, during exercise, metoprolol attenuated the increase in myocardial oxygen
      supply in excess of the reduction in myocardial oxygen demand, as evidenced by a
      progressive decrease in coronary venous Po(2). Consequently, metoprolol caused a
      clockwise rotation of the relationship between myocardial oxygen consumption and
      coronary venous Po(2). Additional beta(2)-adrenoceptor blockade with propranolol
      further inhibited myocardial oxygen supply during exercise, resulting in a
      further clockwise rotation of the relationship between myocardial oxygen
      consumption and coronary venous Po(2). In conclusion, both beta(1)- and beta(2)
      adrenoceptors contribute to the beta-feedforward coronary resistance vessel
      dilation during exercise.

PMID- 20035032
TI  - Decreased rates of substrate oxidation ex vivo predict the onset of heart failure
      and contractile dysfunction in rats with pressure overload.
AB  - AIMS: Left ventricular hypertrophy is a risk factor for heart failure. However,
      it also is a compensatory response to pressure overload, accommodating for
      increased workload. We tested whether the changes in energy substrate metabolism
      may be predictive for the development of contractile dysfunction. METHODS AND
      RESULTS: Chronic pressure overload was induced in Sprague-Dawley rats by aortic
      arch constriction for 2, 6, 10, or 20 weeks. Contractile function in vivo was
      assessed by echocardiography and by invasive pressure measurement. Glucose and
      fatty acid oxidation as well as contractile function ex vivo were assessed in the
      isolated working heart, and respiratory capacity was measured in isolated cardiac
      mitochondria. Pressure overload caused progressive hypertrophy with normal
      ejection fraction (EF) at 2, 6, and 10 weeks, and hypertrophy with dilation and
      impaired EF at 20 weeks. The lung-to-body weight ratio, as marker for pulmonary
      congestion, was normal at 2 weeks (indicative of compensated hypertrophy) but
      significantly increased already after 6 and up to 20 weeks, suggesting the
      presence of heart failure with normal EF at 6 and 10 weeks and impaired EF at 20
      weeks. Invasive pressure measurements showed evidence for contractile dysfunction
      already after 6 weeks and ex vivo cardiac power was reduced even at 2 weeks.
      Importantly, there was impairment in fatty acid oxidation beginning at 2 weeks,
      which was associated with a progressive decrease in glucose oxidation. In
      contrast, respiratory capacity of isolated mitochondria was normal until 10 weeks
      and decreased only in hearts with impaired EF. CONCLUSION: Pressure overload
      induced impairment in fatty acid oxidation precedes the onset of congestive heart
      failure but mitochondrial respiratory capacity is maintained until the EF
      decreases in vivo. These temporal relations suggest a tight link between impaired
      substrate oxidation capacity in the development of heart failure and contractile
      dysfunction and may imply therapeutic and prognostic value.

PMID- 20035033
TI  - Increment and impairment of adiponectin in renal failure.
AB  - AIMS: Patients with chronic renal failure are at high risk of cardiovascular
      diseases. Previous studies in healthy population showed that hypoadiponectinemia
      was associated with high cardiovascular disease risk. However, plasma adiponectin
      (APN) levels are increased in renal dysfunction. Therefore, the clinical
      significance of plasma APN level in patients with moderate renal dysfunction is
      controversial. The aim of this study was to determine the change of plasma APN
      levels in a mouse model of renal failure and the loss of vasculo-protective
      function of APN in the presence of high cystatin C levels. METHODS AND RESULTS:
      Subtotal (5/6) nephrectomy was performed in APN-knockout (KO) mice and wild-type
      (WT) mice. The procedure in WT mice resulted in the significant increase of
      plasma APN and cystatin C levels. The clearance rate of APN was measured by
      injecting plasma from WT mice into KO mice. The clearance rate was significantly
      decreased in subtotal nephrectomized KO mice compared with sham-operated KO mice.
      Adiponectin protein and mRNA levels in adipose tissue were similar to subtotal
      nephrectomized and sham-operated mice. In cultured endothelial cells, at a high
      concentration corresponding to renal failure, cystatin C abolished the
      suppressive effects of APN on tumour necrosis factor alpha-induced expression of
      monocyte adhesion molecules. CONCLUSION: Plasma APN increases in chronic renal
      failure, at least in part due to low clearance rate. High concentrations of
      cystatin C abolish the vasculo-protective effect of APN.

PMID- 20035034
TI  - Does TREAT give the boot to ESAs in the treatment of CKD anemia?

PMID- 20035035
TI  - The Arabidopsis DSO/ABCG11 transporter affects cutin metabolism in reproductive
      organs and suberin in roots.
AB  - Apart from its significance in the protection against stress conditions, the
      cuticular cover is essential for proper development of the diverse surface
      structures formed on aerial plant organs. This layer mainly consists of a cutin
      matrix, embedded and overlaid with cuticular waxes. Following their biosynthesis
      in epidermal cells, cutin and waxes were suggested to be exported across the
      plasma membrane by ABCG-type transporters such as DSO/ABCG11 to the cell wall and
      further to extracellular matrix. Here, additional aspects of DSO/ABCG11 function
      were investigated, predominantly in reproductive organs, which were not revealed
      in the previous reports. This was facilitated by the generation of a transgenic
      DSO/ABCG11 silenced line (dso-4) that displayed relatively subtle morphological
      and chemical phenotypes. These included altered petal and silique morphology,
      fusion of seeds, and changes in levels of cutin monomers in flowers and siliques.
      The dso-4 phenotypes corresponded to the strong DSO/ABCG11 gene expression in the
      embryo epidermis as well as in the endosperm tissues of the developing seeds.
      Moreover, the DSO/ABCG11 protein displayed polar localization in the embryo
      protoderm. Transcriptome analysis of the dso-4 mutant leaves and stems showed
      that reduced DSO/ABCG11 activity suppressed the expression of a large number of
      cuticle-associated genes, implying that export of cuticular lipids from the
      plasma membrane is a rate-limiting step in cuticle metabolism. Surprisingly, root
      suberin composition of dso-4 was altered, as well as root expression of two
      suberin biosynthetic genes. Taken together, this study provides new insights into
      cutin and suberin metabolism and their role in reproductive organs and roots
      development.

PMID- 20035037
TI  - Phenylpropanoid biosynthesis.
AB  - The general phenylpropanoid metabolism generates an enormous array of secondary
      metabolites based on the few intermediates of the shikimate pathway as the core
      unit. The resulting hydroxycinnamic acids and esters are amplified in several
      cascades by a combination of reductases, oxygenases, and transferases to result
      in an organ and developmentally specific pattern of metabolites, characteristic
      for each plant species. During the last decade, methodology driven targeted and
      non-targeted approaches in several plant species have enabled the identification
      of the participating enzymes of this complex biosynthetic machinery, and revealed
      numerous genes, enzymes, and metabolites essential for regulation and
      compartmentation. Considerable success in structural and computational biology,
      combined with the analytical sensitivity to detect even trace compounds and
      smallest changes in the metabolite, transcript, or enzyme pattern, has
      facilitated progress towards a comprehensive view of the plant response to its
      biotic and abiotic environment. Transgenic approaches have been used to reveal
      insights into an apparently redundant gene and enzyme pattern required for
      functional integrity and plasticity of the various phenylpropanoid biosynthetic
      pathways. Nevertheless, the function and impact of all members of a gene family
      remain to be completely established. This review aims to give an update on the
      various facets of the general phenylpropanoid pathway, which is not only
      restricted to common lignin or flavonoid biosynthesis, but feeds into a variety
      of other aromatic metabolites like coumarins, phenolic volatiles, or hydrolyzable
      tannins.

PMID- 20035038
TI  - Safety and pharmacokinetics of subcutaneously administered rilonacept in patients
      with well-controlled end-stage renal disease (ESRD).
AB  - The safety and pharmacokinetics of a single dose of the IL-1 inhibitor,
      rilonacept (IL-1 Trap; 160 mg, subcutaneously), was studied in a group of 6
      patients with well-controlled end-stage renal disease (ESRD) who were observed
      for a period of 42 days following dosing. The safety of rilonacept administration
      was ascertained by regular monitoring of patients for adverse events, by periodic
      determination of a battery of standard laboratory and hematology tests, and by
      testing for binding and neutralizing antibodies to rilonacept. Two of the 6
      patients had treatment-emergent adverse events that were moderate in intensity
      and unrelated to administration of rilonacept. There were no deaths, serious
      adverse events, or withdrawals due to adverse events. No patient developed
      binding or neutralizing antibodies to rilonacept by the 42nd day postdosing. Mean
      C(max) estimated by a noncompartmental analysis was 17.2 mg/L; t(max,) 2.80 days;
      terminal t(1/2), 7.63 days; and AUC(0-infinity), 199.3 d.mg/L. Comparison of
      these results to those obtained in a population of patients with cryopyrin
      associated periodic syndromes, a group of rare, inherited, autoinflammatory
      disorders (mean [SD] eGFR of 73.1 [13.3] mL/min/1.73m2), shows that ESRD and
      related hemodialysis procedures do not prolong the elimination of rilonacept, and
      therefore no dose adjustment should be needed relative to individuals with normal
      renal function.

PMID- 20035036
TI  - Mild reductions in mitochondrial NAD-dependent isocitrate dehydrogenase activity
      result in altered nitrate assimilation and pigmentation but do not impact growth.
AB  - Transgenic tomato (Solanum lycopersicum) plants were generated expressing a
      fragment of the mitochondrial NAD-dependent isocitrate dehydrogenase gene
      (SlIDH1) in the antisense orientation. The transgenic plants displayed a mild
      reduction in the activity of the target enzyme in the leaves but essentially no
      visible alteration in growth from the wild-type. Fruit size and yield were,
      however, reduced. These plants were characterized by relatively few changes in
      photosynthetic parameters, but they displayed a minor decrease in maximum
      photosynthetic efficiency (Fv/Fm). Furthermore, a clear reduction in flux through
      the tricarboxylic acid (TCA) cycle was observed in the transformants.
      Additionally, biochemical analyses revealed that the transgenic lines exhibited
      considerably altered metabolism, being characterized by slight decreases in the
      levels of amino acids, intermediates of the TCA cycle, photosynthetic pigments,
      starch, and NAD(P)H levels, but increased levels of nitrate and protein. Results
      from these studies show that even small changes in mitochondrial NAD-dependent
      isocitrate dehydrogenase activity lead to noticeable alterations in nitrate
      assimilation and suggest the presence of different strategies by which metabolism
      is reprogrammed to compensate for this deficiency.

PMID- 20035039
TI  - Permeability and concentration of levofloxacin in epithelial lining fluid in
      patients with lower respiratory tract infections.
AB  - The purpose of the study was to assess the bactericidal effects of a single oral
      dose of levofloxacin (LVFX) by examining the concentration of LVFX in alveolar
      epithelial lining fluid (ELF) from patients with lower respiratory tract
      infections (LRTI). Forty patients with LRTI took 500 mg of LVFX and then received
      a fiberoptic bronchoscopic procedure randomly 1, 4, 8, 12, or 24 hours following
      dosing. Bronchoalveolar lavage fluid and blood were collected at the time of the
      bronchopulmonary procedure, and the LVFX concentration was determined. The mean
      peak concentrations of LVFX in plasma and ELF were achieved at 1.5 hours (4.07
      mg/L) and 1 hour (3.44 mg/L), respectively. The AUC(24h) samples were 50.12 mg .
      h/L and 34.51 mg . h/L, respectively. The permeability of LVFX, which was
      estimated based on the ratio of LVFX concentration in tissue fluids to that in
      plasma, was 0.78 on average across all time points. After a single dose of LVFX
      in patients with LRTI, the drug rapidly distributed into bronchopulmonary tissue,
      thereby suggesting this dose is capable of achieving the concentration in target
      organs required for bactericidal efficacy.

PMID- 20035040
TI  - Neoplastic blood cells become pluripotent.

PMID- 20035041
TI  - Increasing the punch of reduced-intensity transplants.

PMID- 20035042
TI  - CCL2/CCR2: push/pull for migration.

PMID- 20035043
TI  - Getting in shape with RanBP10.

PMID- 20035044
TI  - Complement: help or hindrance?

PMID- 20035046
TI  - Birth order and outcome after HLA-identical sibling donor transplantation.

PMID- 20035047
TI  - Anti-Fas gene therapy prevents doxorubicin-induced acute cardiotoxicity through
      mechanisms independent of apoptosis.
AB  - Activation of Fas signaling is a key mediator of doxorubicin cardiotoxicity,
      which involves both cardiomyocyte apoptosis and myocardial inflammation. In this
      study, acute cardiotoxicity was induced in mice by doxorubicin, and some mice
      simultaneously received an intramuscular injection of adenoviral vector encoding
      mouse soluble Fas (sFas) gene (Ad.CAG-sFas), an inhibitor of Fas/Fas ligand
      interaction. Two weeks later, left ventricular dilatation and dysfunction were
      apparent in the LacZ-treated control group, but both were significantly mitigated
      in the sFas-treated group. The in situ nick-end labeling-positive rate were
      similar in the two groups, and although electron microscopy revealed
      cardiomyocyte degeneration, no apoptotic structural features and no activation of
      caspases were detected, suggesting an insignificant role of apoptosis in this
      model. Instead, sFas treatment reversed doxorubicin-induced down-regulation of
      GATA-4 and attenuated ubiquitination of myosin heavy chain and troponin I to
      preserve these sarcomeric proteins. In addition, doxorubicin-induced significant
      leukocyte infiltration, fibrosis, and oxidative damage to the myocardium, all of
      which were largely reversed by sFas treatment. sFas treatment also suppressed
      doxorubicin-induced p53 overexpression, phosphorylation of c-Jun N-terminal
      kinase, c-Jun, and inhibitor of nuclear factor-kappaB, as well as production of
      cyclooxygenase-2 and monocyte chemoattractant protein-1, and it restored
      extracellular signal-regulated kinase activation. Therefore, sFas gene therapy
      prevents the progression of doxorubicin-induced acute cardiotoxicity, with
      accompanying attenuation of the cardiomyocyte degeneration, inflammation,
      fibrosis, and oxidative damage caused by Fas signaling.

PMID- 20035048
TI  - CNS elevation of vascular and not mucosal addressin cell adhesion molecules in
      patients with multiple sclerosis.
AB  - The mucosal addressin cell adhesion molecule (MAdCAM) and vascular cell adhesion
      molecule (VCAM) appear to play roles in the recruitment of leukocytes to
      specialized endothelium lining the gastrointestinal tract. The purpose of this
      study was to clarify the role of MAdCAM and VCAM in the central nervous system by
      comparing protein expression in patients with multiple sclerosis (MS) and control
      subjects by immunohistochemistry. Specific antibodies to human VCAM and MAdCAM
      were used to confirm expression in control and MS nervous system specimens by
      immunohistochemistry. VCAM immunoreactivity was detected in endothelial cells,
      perivascular tissue, and in some cases, leukocytes within the meninges, gray, and
      white matter, of both controls and MS patients. VCAM immunoreactivity was maximal
      in a patient with acute active plaques, but of lower intensity and reduced
      distribution in controls and those with chronic active or inactive MS plaques. In
      contrast, MAdCAM immunoreactivity could not be detected in brain tissue from
      unaffected or MS patients. Taken together, these data support a role of VCAM, but
      not MAdCAM in the development of MS.

PMID- 20035049
TI  - Mast cell-derived TNF can exacerbate mortality during severe bacterial infections
      in C57BL/6-KitW-sh/W-sh mice.
AB  - We used mast cell-engrafted genetically mast cell-deficient C57BL/6-Kit(W-sh/W
      sh) mice to investigate the roles of mast cells and mast cell-derived tumor
      necrosis factor in two models of severe bacterial infection. In these mice, we
      confirmed findings derived from studies of mast cell-deficient WBB6F(1)-Kit(W/W
      v) mice indicating that mast cells can promote survival in cecal ligation and
      puncture (CLP) of moderate severity. However, we found that the beneficial role
      of mast cells in this setting can occur independently of mast cell-derived tumor
      necrosis factor. By contrast, using mast cell-engrafted C57BL/6-Kit(W-sh/W-sh)
      mice, we found that mast cell-derived tumor necrosis factor can increase
      mortality during severe CLP and can also enhance bacterial growth and hasten
      death after intraperitoneal inoculation of Salmonella typhimurium. In WBB6F(1)
      Kit(W-sh/W-sh) mice, mast cells enhanced survival during moderately severe CLP
      but did not significantly change the survival observed in severe CLP. Our
      findings in three types of genetically mast cell-deficient mice thus support the
      hypothesis that, depending on the circumstances (including mouse strain
      background, the nature of the mutation resulting in a mast cell deficiency, and
      type and severity of infection), mast cells can have either no detectable effect
      or opposite effects on survival during bacterial infections, eg, promoting
      survival during moderately severe CLP associated with low mortality but, in
      C57BL/6-Kit(W-sh/W-sh) mice, increasing mortality during severe CLP or infection
      with S. typhimurium.

PMID- 20035050
TI  - Perforin-independent extracellular granzyme B activity contributes to abdominal
      aortic aneurysm.
AB  - Granzyme B (GZMB) is a serine protease that is abundantly expressed in advanced
      human atherosclerotic lesions and may contribute to plaque instability. Perforin
      is a pore-forming protein that facilitates GZMB internalization and the induction
      of apoptosis. Recently a perforin-independent, extracellular role for GZMB has
      been proposed. In the current study, the role of GZMB in abdominal aortic
      aneurysm (AAA) was assessed. Apolipoprotein E (APOE)(-/-) x GZMB(-/-) and APOE(-/
      ) x perforin(-/-) double knockout (GDKO, PDKO) mice were generated to test
      whether GZMB exerted a causative role in aneurysm formation. To induce aneurysm,
      mice were given angiotensin II (1000 ng/kg/min) for 28 days. GZMB was found to be
      abundant in both murine and human AAA specimens. GZMB deficiency was associated
      with a decrease in AAA and increased survival compared with APOE-KO and PDKO
      mice. Although AAA rupture was observed frequently in APOE-KO (46.7%; n = 15) and
      PDKO (43.3%; n = 16) mice, rupture was rarely observed in GDKO (7.1%; n = 14)
      mice. APOE-KO mice exhibited reduced fibrillin-1 staining compared with GDKO
      mice, whereas in vitro protease assays demonstrated that fibrillin-1 is a
      substrate of GZMB. As perforin deficiency did not affect the outcome, our results
      suggest that GZMB contributes to AAA pathogenesis via a perforin-independent
      mechanism involving extracellular matrix degradation and subsequent loss of
      vessel wall integrity.

PMID- 20035051
TI  - Oncoprotein Bmi-1 renders apoptotic resistance to glioma cells through activation
      of the IKK-nuclear factor-kappaB Pathway.
AB  - One of the features of malignant gliomas is their deviant resistance to cellular
      apoptosis induced by cytotoxic reagents. Bmi-1, an oncoprotein, has been linked
      to oncogenesis and cancer progression in various types of human cancers including
      gliomas. However, the mechanisms underlying Bmi-1 antiapoptotic function remain
      largely unknown. In this study, we report that Bmi-1 renders apoptotic resistance
      to glioma cells through nuclear factor-kappaB (NF-kappaB). In glioma cells,
      ectopic expression of Bmi-1 significantly inhibits doxorubicin-, BCNU-, or UV
      irradiation- induced apoptosis through reduction of activated caspase-3 and PARP,
      and induction of Bcl-X(L). Cellular depletion of Bmi-1 enhances the sensitivity
      of glioma cells to apoptosis induced by doxorubicin, BCNU, or UV irradiation. Bmi
      1 activates NF-kappaB through stimulation of IkappaB phosphorylation, nuclear
      translocation, and transcriptional activity of NF-kappaB and expression of
      downstream genes of NF-kappaB including caspase-3, PARP, Bcl-X(L), and c-Myc.
      Inhibition of the IKK-NF-kappaB pathway abrogates the antiapoptotic effect of Bmi
      1 on glioma cells. In high-grade gliomas, Bmi-1 and NF-kappaB are co-expressed in
      the cell nucleus. Up-regulation of Bmi-1 also correlates with tumor progression
      and poor survival of patients with gliomas. Together, our data demonstrate that
      Bmi-1 bestows apoptotic resistance to glioma cells through the IKK-NF-kappaB
      pathway and suggest Bmi-1 as a useful indicator for glioma prognosis.

PMID- 20035052
TI  - Prenatal exposure to apoE deficiency and postnatal hypercholesterolemia are
      associated with altered cell-specific lysine methyltransferase and histone
      methylation patterns in the vasculature.
AB  - We recently demonstrated that neointima formation of adult heterozygous
      apolipoprotein E (apoE(+/-)) offspring from hypercholesterolemic apoE(-/-)
      mothers was significantly increased as compared with genetically identical
      apoE(+/-) offspring from normocholesterolemic wild-type mothers. Since
      atherosclerosis is the consequence of a complex microenvironment and local
      cellular interactions, the effects of in utero programming and type of postnatal
      diet on epigenetic histone modifications in the vasculature were studied in both
      groups of offspring. An immunohistochemical approach was used to detect cell
      specific histone methylation modifications and expression of accompanying lysine
      methyltransferases in the carotid arteries. Differences in histone triple
      methylation modifications in vascular endothelial and smooth muscle cells
      revealed that the offspring from apoE(-/-) mothers had significantly different
      responses to a high cholesterol diet when compared with offspring from wild-type
      mothers. Our results suggest that both in utero programming and postnatal
      hypercholesterolemia affect epigenetic patterning in the vasculature, thereby
      providing novel insights regarding initiation and progression of vascular disease
      in adults.

PMID- 20035053
TI  - Remodeling of the fetal collecting duct epithelium.
AB  - Congenital urinary tract obstruction induces changes to the renal collecting duct
      epithelium, including alteration and depletion of intercalated cells. To study
      the effects of obstruction on the ontogeny of intercalated cell development, we
      examined normal and obstructed human fetal and postnatal kidneys. In the normal
      human fetal kidney, intercalated cells originated in the medullary collecting
      duct at 8 weeks gestation and remained most abundant in the inner medulla
      throughout gestation. In the cortex, intercalated cells were rare at 18 and 26
      weeks gestation and observed at low abundance at 36 weeks gestation. Although
      early intercalated cells exhibit an immature phenotype, Type A intercalated cells
      predominated in the inner and outer medullae at 26 and 36 weeks gestation with
      other intercalated cell subtypes observed rarely. Postnatally, the collecting
      duct epithelium underwent a remodeling whereby intercalated cells become abundant
      in the cortex yet absent from the inner medulla. In 18-week obstructed kidneys
      with mild to moderate injury, the intercalated cells became more abundant and
      differentiated than the equivalent age-matched normal kidney. In contrast, more
      severely injured ducts of the late obstructed kidney exhibited a significant
      reduction in intercalated cells. These studies characterize the normal ontogeny
      of human intercalated cell development and suggest that obstruction induces
      premature remodeling and differentiation of the fetal collecting duct epithelium.

PMID- 20035054
TI  - Persistent hijacking of brain proteasomes in HIV-associated dementia.
AB  - Immunoproteasome induction sustains class 1 antigen presentation and
      immunological vigilance against HIV-1 in the brain. Investigation of HIV-1
      associated alterations in brain protein turnover by the ubiquitin-proteasome
      system was performed by (1) determining proteasome subunit changes associated
      with persistent brain inflammation due to HIV-1; (2) determining whether these
      changes are related to HIV-1 neurocognitive disturbances, encephalitis, and viral
      loads; and (3) localizing proteasome subunits in brain cells and synapses. On the
      basis of neurocognitive performance, virological, and immunological measurements
      obtained within 6 months before death, 153 autopsy cases were selected.
      Semiquantitative immunoblot analysis performed in the dorsolateral prefrontal
      cortex revealed up to threefold induction of immunoproteasome subunits LMP7 and
      PA28alpha in HIV-1-infected subjects and was strongly related to diagnoses of
      neuropsychological impairment and HIV encephalitis. Low performance on
      neurocognitive tests specific for dorsolateral prefrontal cortex functioning
      domains was selectively correlated with immunoproteasome induction.
      Immunohistochemistry and laser confocal microscopy were then used to localize
      immunoproteasome subunits to glial and neuronal elements including perikarya,
      dystrophic axons, and synapses. In addition, HIV loads in brain tissue,
      cerebrospinal fluid, and blood plasma were robustly correlated to
      immunoproteasome levels. This persistent "hijacking" of the proteasome by HIV-1
      mediated inflammatory response and immunoproteasome induction in the brain is
      hypothesized to impede turnover of folded proteins in brain cells. This would
      disrupt neuronal and synaptic protein dynamics, contributing to HIV-1
      neurocognitive disturbances.

PMID- 20035056
TI  - Structural typing of systemic amyloidoses by luminescent-conjugated polymer
      spectroscopy.
AB  - Most systemic amyloidoses are progressive and lethal, and their therapy depends
      on the identification of the offending proteins. Here we report that luminescent
      conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The
      heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid
      (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid
      deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid
      emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral
      composition of the emitted light, thereby reporting ligand-induced steric
      changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological
      tissue arrays revealed striking spectral differences between specimens. Blinded
      cluster assignments of spectral profiles of tissue samples from 108 tissue
      samples derived from 96 patients identified three nonoverlapping classes, which
      were found to match AA, AL, and ATTR immunotyping. We conclude that LCP
      spectroscopy is a sensitive and powerful tool for identifying and characterizing
      amyloid deposits.

PMID- 20035055
TI  - Biglycan and fibromodulin have essential roles in regulating chondrogenesis and
      extracellular matrix turnover in temporomandibular joint osteoarthritis.
AB  - The temporomandibular joint is critical for jaw movements and allows for
      mastication, digestion of food, and speech. Temporomandibular joint
      osteoarthritis is a degenerative disease that is marked by permanent cartilage
      destruction and loss of extracellular matrix (ECM). To understand how the ECM
      regulates mandibular condylar chondrocyte (MCC) differentiation and function, we
      used a genetic mouse model of temporomandibular joint osteoarthritis that is
      deficient in two ECM proteins, biglycan and fibromodulin (Bgn(-/0)Fmod(-/-)).
      Given the unavailability of cell lines, we first isolated primary MCCs and found
      that they were phenotypically unique from hyaline articular chondrocytes isolated
      from the knee joint. Using Bgn(-/0) Fmod(-/-) MCCs, we discovered the early basis
      for temporomandibular joint osteoarthritis arises from abnormal and accelerated
      chondrogenesis. Transforming growth factor (TGF)-beta1 is a growth factor that is
      critical for chondrogenesis and binds to both biglycan and fibromodulin. Our
      studies revealed the sequestration of TGF-beta1 was decreased within the ECM of
      Bgn(-/0) Fmod(-/-) MCCs, leading to overactive TGF-beta1 signal transduction.
      Using an explant culture system, we found that overactive TGF-beta1 signals
      induced chondrogenesis and ECM turnover in this model. We demonstrated for the
      first time a comprehensive study revealing the importance of the ECM in
      maintaining the mandibular condylar cartilage integrity and identified biglycan
      and fibromodulin as novel key players in regulating chondrogenesis and ECM
      turnover during temoporomandibular joint osteoarthritis pathology.

PMID- 20035057
TI  - Deregulation of growth factor, circadian clock, and cell cycle signaling in
      regenerating hepatocyte RXRalpha-deficient mouse livers.
AB  - Activation of the nuclear receptors constitutive androstane receptor, pregnane X
      receptor, and peroxisome proliferator-activated receptor alpha results in
      hepatomegaly, and these nuclear receptors are implicated in the regulation of
      liver regeneration. Retinoid X receptor (RXR)alpha is an essential partner of
      these nuclear receptors. Therefore, we studied the role of hepatocyte RXRalpha in
      liver regeneration using partial hepatectomy model. The results showed that
      hepatocyte RXRalpha deficiency caused an approximately 20-hour delay in
      hepatocyte proliferation after partial hepatectomy. Several pathways, including
      growth factors and the circadian cell cycle, were impaired due to hepatocyte
      RXRalpha deficiency. In addition, the expression patterns of hepatocyte growth
      factor, fibroblast growth factor 2, platelet-derived growth factor, and
      transforming growth factor alpha were altered due to lack of RXRalpha.
      Furthermore, the peroxisome proliferator-activated receptor alpha/brain and
      muscle Arnt-like protein 1/Rev-erbalpha/P21 pathway was compromised, and
      Cry1/Cry2 and Wee1/Per1 expression was deregulated in regenerating RXRalpha-null
      livers. Accordingly, the expression and regulation of cyclin D1/Cyclin- dependent
      Kinase (Cdk)4, cyclin E1/Cdk2, cyclin A2/Cdk2, and cyclin B1/Cdk1 after partial
      hepatectomy were altered in regenerating RXRalpha-null livers. Hepatocyte
      RXRalpha deficiency also affected the basal, as well as regeneration-induced
      cyclin E1 expression levels. Activation of RXRalpha by retinoic acids increased
      the cyclin E1 promoter activity indicating retinoic acid-mediated signaling
      positively controls cyclin E1 gene expression. As many of these observed changes
      were not documented in the regenerating livers of other nuclear receptor knockout
      mice, these observed effects may be hepatocyte RXRalpha specific.

PMID- 20035058
TI  - Laminin alpha4-null mutant mice develop chronic kidney disease with persistent
      overexpression of platelet-derived growth factor.
AB  - Each extracellular matrix compartment in the kidney has a unique composition,
      with regional specificity in the expression of various laminin isoforms. Although
      null mutations in the majority of laminin chains lead to specific developmental
      abnormalities in the kidney, Lama4-/- mice have progressive glomerular and
      tubulointerstitial fibrosis. These mice have a significant increase in expression
      of platelet-derived growth factor (PDGF)-BB, PDGF-DD, and PDGF receptor beta in
      association with immature glomerular and peritubular capillaries. In addition,
      mesangial cell exposure to alpha4-containing laminins, but not other isoforms,
      results in down-regulation of PDGF receptor mRNA and protein, suggesting a direct
      effect of LN411/LN421 on vessel maturation. Given the known role of
      overexpression of PDGF-BB and PDGF-DD on glomerular and tubulointerstitial
      fibrosis, these data suggest that failure of laminin alpha4-mediated down
      regulation of PDGF activity contributes to the progressive renal lesions in this
      animal model. Given the recent demonstration that individuals with laminin alpha4
      mutations develop cardiomyopathy, these findings may be relevant to kidney
      disease in humans.

PMID- 20035059
TI  - Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast
      formation associated with oral cancers: significance of interleukin-6 synthesized
      by stromal cells in response to cancer cells.
AB  - We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related
      peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast
      formation. Microarray analyses performed on 43 human OSCC specimens revealed that
      many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6
      mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in
      cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface.
      Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM)
      derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u
      1) stimulated Rankl expression in stromal cells and osteoclast formation.
      Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in
      ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although
      the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody.
      CM derived from all of the OSCC cell lines effectively induced IL-6 expression in
      stromal cells, and the induction was partially blocked by anti-PTHrP antibody.
      Xenografts of HSC3 cells onto the periosteal region of the parietal bone in
      athymic mice presented histology and expression profiles of RANKL and IL-6
      similar to those observed in bone-invasive human OSCC specimens. These results
      indicate that OSCC provides a suitable microenvironment for osteoclast formation
      not only by producing IL-6 and PTHrP but also by stimulating stromal cells to
      synthesize IL-6.

PMID- 20035060
TI  - Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the
      development of endometriosis.
AB  - Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo
      retrograde transport to the peritoneal cavity is considered an important factor
      in the development of endometriosis. However, the mechanisms responsible for the
      loss of function of macrophages remain largely unknown. Herein, we report that
      prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway,
      inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced
      phagocytic ability. PGE(2)-mediated inhibition of macrophage phagocytic
      capability was restored by ectopic expression of CD36. Treatment with PGE(2)
      inhibited CD36-dependent phagocytosis of peritoneal macrophages and increased the
      number and size of endometriotic lesions in mice. In contrast, blockade of PGE(2)
      production by cyclooxygenase inhibitors enhanced the phagocytic ability of
      peritoneal macrophages and reduced endometriotic lesion formation. Taken
      together, our findings reveal a potential mechanism of immune dysfunction during
      endometriosis development and may contribute to the design of an effective
      prevention/treatment regimen.

PMID- 20035061
TI  - Point: Left ventricular volume during diastasis is the physiological in vivo
      equilibrium volume and is related to diastolic suction.

PMID- 20035062
TI  - Continuous estimates of dynamic cerebral autoregulation during transient
      hypocapnia and hypercapnia.
AB  - Dynamic cerebral autoregulation (CA) is the transient response of cerebral blood
      flow (CBF) to rapid blood pressure changes: it improves in hypocapnia and becomes
      impaired during hypercapnia. Batch-processing techniques have mostly been used to
      measure CA, providing a single estimate for an entire recording. A new approach
      to increase the temporal resolution of dynamic CA parameters was applied to
      transient hypercapnia and hypocapnia to describe the time-varying properties of
      dynamic CA during these conditions. Thirty healthy subjects (mean +/- SD: 25 +/-
      6 yr, 9 men) were recruited. CBF velocity was recorded in both middle cerebral
      arteries (MCAs) with transcranial Doppler ultrasound. Arterial blood pressure
      (Finapres), end-tidal CO(2) (ET(CO(2)); infrared capnograph), and a three-lead
      ECG were also measured at rest and during repeated breath hold and
      hyperventilation. A moving window autoregressive moving average model provided
      continuous values of the dynamic CA index [autoregulation index (ARI)] and
      unconstrained gain. Breath hold led to significant increase in ET(CO(2)) (+5.4 +/
      6.1 mmHg), with concomitant increase in CBF velocity in both MCAs. Continuous
      dynamic CA parameters showed highly significant changes (P < 0.001), with a
      temporal pattern reflecting a delayed dynamic response of CA to changes in
      arterial Pco(2) and a maximal reduction in ARI of -5.1 +/- 2.4 and -5.1 +/- 2.3
      for the right and left MCA, respectively. Hyperventilation led to a marked
      decrease in ET(CO(2)) (-7.2 +/- 4.1 mmHg, P < 0.001). Unexpectedly, CA efficiency
      dropped significantly with the inception of the metronome-controlled
      hyperventilation, but, after approximately 30 s, the ARI increased gradually to
      show a maximum change of 5.7 +/- 2.9 and 5.3 +/- 3.0 for the right and left MCA,
      respectively (P < 0.001). These results confirm the potential of continuous
      estimates of dynamic CA to improve our understanding of human cerebrovascular
      physiology and represent a promising new approach to improve the sensitivity of
      clinical applications of dynamic CA modeling.

PMID- 20035063
TI  - Mylohyoid discharge of the in situ rat: a probe of pontile respiratory activities
      in eupnea and gasping.
AB  - Our purpose was to characterize respiratory-modulated activity of the mylohyoid
      nerve. Since its motoneurons are in the trigeminal motor nucleus, mylohyoid
      discharge could serve as a probe of the role of pontile mechanisms in the
      generation of respiratory rhythms. Studies were performed in the decerebrate,
      perfused in situ preparation of the rat. Phrenic discharge was recorded as the
      index of the respiratory rhythm. In eupnea, the mylohyoid nerve discharged
      primarily during neural expiration, in the period between phrenic bursts. This
      expiratory discharge increased greatly in hypoxia and fell in hypercapnia. The
      hypoxia-induced increase in mylohyoid discharge was due, at least in part, to a
      direct influence of hypoxia on the brain stem. In ischemia, phrenic discharge
      increased, and then declined to apnea, which was succeeded by gasping. The
      mylohyoid nerve discharged tonically during the apneic period, but still declined
      during each of the phrenic bursts of gasping. This maintenance of a respiratory
      modulation of the mylohyoid discharge in gasping supports the concept that a
      release of medullary mechanisms, rather than a ubiquitous suppression of pontile
      influences, underlies the neurogenesis of gasping. Results also provide
      additional support for our conclusion that activity of any single cranial nerve
      does not provide an accurate index of the type of respiratory rhythm, be it
      eupnea or gasping.

PMID- 20035064
TI  - Contraction-by-contraction VO2 and computer-controlled pump perfusion as novel
      techniques to study skeletal muscle metabolism in situ.
AB  - The purpose of this research was to develop new techniques to 1) rapidly sample
      venous O(2) saturation to determine contraction-by-contraction oxygen uptake
      (Vo(2)), and 2) precisely control the rate and pattern of blood flow adjustment
      from one chosen steady state to another. An indwelling inline oximeter probe
      connected to an Oximetrix 3 meter was used to sample venous oxygen concentration
      ([O(2)]) (via fractional saturation of Hb with O(2)). Data from the Oximetrix 3
      were filtered, deconvolved, and processed by a moving average second by second.
      Computer software and a program written in-house were used to control blood flow
      with a peristaltic pump. The isolated canine gastrocnemius muscle complex (GS) in
      situ was utilized to test these techniques. A step change in metabolic rate was
      elicited by stimulating GS muscles via their sciatic nerves (supramaximal
      voltage, 8 V; 50 Hz, 0.2-ms pulse width; train duration 200 ms) at a rate of
      either 1 contraction/2 s, or 2 contractions/3 s. With arterial [O(2)] maintained
      constant, blood flow and calculated venous [O(2)] were averaged over each
      contraction cycle and used in the Fick equation to calculate contraction-by
      contraction Vo(2). About 5-8 times more data points were obtained with this
      method compared with traditional manual sampling. Software-controlled pump
      perfusion enabled the ability to mimic spontaneous blood flow on-kinetics (tau:
      14.3 s) as well as dramatically speed (tau: 2.0 s) and slow (tau: 63.3 s) on
      kinetics. These new techniques significantly improve on existing methods for
      mechanistically altering blood flow kinetics as well as accurately measuring
      muscle oxygen consumption kinetics during transitions between metabolic rates.

PMID- 20035065
TI  - Acclimation to decompression sickness in rats.
AB  - Protection against decompression sickness (DCS) by acclimation to hyperbaric
      decompression has been hypothesized but never proven. We exposed rats to
      acclimation dives followed by a stressful "test" dive to determine whether
      acclimation occurred. Experiments were divided into two phases. Phase 1 rats were
      exposed to daily acclimation dives of hyperbaric air for 30 min followed by rapid
      decompression on one of the following regimens: 70 ft of seawater (fsw) for 9
      days (L70), 70 fsw for 4 days (S70), 40 fsw for 9 days (L40), 40 fsw for 4 days
      (S40), or unpressurized sham exposure for 9 days (Control). On the day following
      the last exposure, all were subjected to a "test" dive (175 fsw, 60 min, rapid
      decompression). Both L70 and S70 rats had significantly lower incidences of DCS
      than Control rats (36% and 41% vs. 62%, respectively). DCS incidences for the
      other regimens were lower than in Control rats but without statistical
      significance. Phase 2 used the most protective regimen from phase 1 (L70); rats
      were exposed to L70 or a similar regimen with a less stressful staged
      decompression. Another group was exposed to a single acclimation dive (70 fsw/30
      min) on the day before the test dive. We observed a nonsignificant trend for the
      rapidly decompressed L70 dives to be more protective than staged decompression
      dives (44% vs. 51% DCS incidence). The single acclimation dive regimen did not
      provide protection. We conclude that protection against DCS can be attained with
      acclimating exposures that do not themselves cause DCS. The deeper acclimation
      dive regimens (70 fsw) provided the most protection.

PMID- 20035066
TI  - Analysis of isovolumic relaxation in failing hearts by monoexponential time
      constants overestimates lusitropic change and load dependence: mechanisms and
      advantages of alternative logistic fit.
AB  - BACKGROUND: Failing hearts display slow relaxation with apparent increased load
      sensitivity. However, inaccuracies of monoexponential analysis can contribute to
      these observations, and different qualitative and quantitative results might be
      obtained by alternative models. We tested whether pressure relaxation of failing
      hearts consistently deviates from a monoexponential waveform, leading to
      overestimations of lusitropic change and load sensitivity by monoexponential
      derived time constants. METHODS AND RESULTS: Fourteen dogs were studied before
      and after tachycardia pacing-induced heart failure. Relaxation time constants
      were derived by monoexponential fits (tau(E)) with zero or nonzero asymptotes and
      by a logistic fit (tau(L)). tau(L) assumes nonlinear relations between pressure
      and its first derivative, whereas tau(E) assumes a linear dependence. Load
      sensitivity of tau was tested by comparing beats during vena caval occlusion.
      tau(E) prolonged by 75% to 80% with heart failure, 3 times more than tau(L)
      (P<0.01). tau(E) displayed marked load sensitivity in failing hearts, shortening
      during preload reduction, whereas tau(L) was little changed by the same loading
      maneuver. Neither tau(L) nor tau(E) varied with preload in control hearts. The
      discrepancy between tau(E) and tau(L) results was due to nonmonoexponential decay
      reflected by nonlinear pressure-time derivative of pressure plots, which was
      enhanced with heart failure (P<0.01). This nonlinearity was reduced by beta
      adrenergic stimulation, lowering preload sensitivity of tau(E) to control levels.
      CONCLUSIONS: Isovolumic relaxation in failing hearts deviates from a
      monoexponential waveform, leading to overestimated relaxation delay and increased
      load sensitivity of monoexponential time constants. This deviation is under beta
      adrenergic modulation. The logistic model improves the fit-to-real pressure decay
      in failing hearts, providing more stable measures of relaxation.

PMID- 20035067
TI  - We are on the clock: MRI as a surrogate marker of lesion age in acute ischemic
      stroke.

PMID- 20035068
TI  - Fluid-attenuated inversion recovery evolution within 12 hours from stroke onset:
      a reliable tissue clock?
AB  - BACKGROUND AND PURPOSE: It has recently been proposed that fluid-attenuated
      inversion recovery (FLAIR) imaging may serve as a surrogate marker for time of
      symptom onset after stroke. We assessed the hypothesis that FLAIR imaging could
      be used to decide if an MRI was performed within 4.5 hours from symptom onset or
      later. METHODS: All consecutive patients with presumed stroke who underwent an
      MRI within 12 hours after known symptom onset were included regardless of stroke
      subtype and severity between May 2008 and May 2009. Blinded to time of symptom
      onset, 2 raters judged the visibility of lesions on FLAIR. Apparent diffusion
      coefficient values, lesion volume on diffusion-weighted imaging, and relative
      signal intensity of FLAIR lesions were determined. RESULTS: In 94 consecutive
      patients with stroke, we found that median time from symptom onset for FLAIR
      positive patients (189 minutes; interquartile range, 110 to 369 minutes) was
      significantly longer compared with FLAIR-negative patients (103 minutes;
      interquartile range, 75 to 183 minutes; P=0.011). Negative FLAIR had a
      sensitivity of 46% and a specificity of 79% for allocating patients to a time
      window of less than 4.5 hours. FLAIR positivity increased with diffusion-weighted
      imaging lesion volume (P<0.001) but showed no correlation with apparent diffusion
      coefficient values (P=0.795). There was no significant correlation between
      relative signal intensity and time from symptom onset (Spearman correlation
      coefficient -0.152, P=0.128). CONCLUSIONS: Based on our findings, we cannot
      recommend the use of FLAIR visibility as an estimate of time from symptom onset
      within the first 4.5 hours.

PMID- 20035069
TI  - MRI of stroke recovery.
AB  - MRI is a vital tool for the measurement of acute stroke and has been used to
      visualize changes in activation patterns during stroke recovery. There is
      emerging interest on using MRI to monitor the structural substrates of
      spontaneous recovery and neurorestorative treatment of stroke. In this review, we
      describe the use of MRI and its associated challenges to measure vascular and
      neuronal remodeling in response to spontaneous and therapy-induced stroke
      recovery. We demonstrate that MRI methodologies may be used in real-time
      monitoring of recovery from stroke.

PMID- 20035070
TI  - Tuberculosis and the risk of ischemic stroke: a 3-year follow-up study.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to estimate the risk of ischemic
      stroke during a 3-year follow-up period after a tuberculosis diagnosis using a
      nationwide, population-based study and a retrospective cohort design. METHOD: The
      study cohort comprised 2283 patients who had received treatment for tuberculosis,
      except tuberculosis of the meninges and central nervous system, between 2000 and
      2003; 6849 randomly selected subjects comprised the comparison cohort. Cox
      proportional hazard regressions were performed as a means of comparing the 3-year
      ischemic stroke-free survival rate between these 2 cohorts. RESULTS: Of the 9132
      sampled patients, 392 (4.3%) experienced ischemic stroke during the 3-year follow
      up period, including 136 (6.0% of the tuberculosis patients) from the study
      cohort and 256 (3.7%) from the comparison cohort. After adjusting for patient
      age, gender, hypertension, diabetes, coronary heart disease, hyperlipidemia,
      malignancy, monthly income, and the geographical region and urbanization level of
      the community in which the patient resided, the hazard ratio of ischemic stroke
      for tuberculosis patients was 1.52-times (95% CI, 1.21-1.91; P<0.001) higher than
      for comparison patients. CONCLUSIONS: We conclude that patients with a
      tuberculosis diagnosis are at an increased risk for ischemic stroke but not
      hemorrhagic stroke in the next 3 years. Further research is necessary to
      investigate these findings in tuberculosis-endemic areas.

PMID- 20035072
TI  - Boosting the chances to improve stroke treatment.
AB  - BACKGROUND AND PURPOSE: There is a lack of agreement regarding measuring the
      effects of stroke treatment in clinical trials, which often relies on the
      dichotomized value of 1 outcome scale. Alternative analyses consist mainly of 2
      strategies: use all the information from an ordinal scale and combine information
      from several outcome scales in a single estimate. METHODS: We reanalyzed 3
      outcome scales that assessed patient recovery (modified Rankin Scale, National
      Institutes of Health Stroke Scale, and Barthel Index). With data collected from
      the 1652 patients in the Citicoline pooling data analysis, we used 2 standard
      techniques of exploratory multivariate analysis to analyze the distances among
      ranks and to isolate the common and the unique information provided by each of
      the 3 scales. RESULTS: The different scale values correspond to gradually
      different patient status, confirming that information is lost when a scale is
      collapsed to just 2 values, whether recovered or not. The scales shared 90.7%
      (95% CI, 84.5-96.9) of their information, with no individual scale contributing
      unique information. CONCLUSIONS: Salient stroke outcome information is lost when
      an ordinal scale is collapsed into fewer categories. In contrast, the full scales
      provide a comprehensive patient outcome estimate. Furthermore, in the context of
      stroke clinical trials, those scales are highly correlated, providing the
      rationale to pool them into a single estimate. These insights may be used to
      optimize the analysis of stroke trials to increase study power to detect
      efficacious interventions.

PMID- 20035071
TI  - Frequency and determinants of lipid testing in ischemic stroke and transient
      ischemic attack: findings from get with the guidelines-stroke.
AB  - BACKGROUND AND PURPOSE: National guidelines recommend lipid testing for all
      patients with ischemic stroke and transient ischemic attack. This study examined
      the frequency and predictors for in-hospital low-density lipoprotein testing
      using data from a nationwide stroke registry. METHODS: Between 2003 and 2008, Get
      With The Guideline-Stroke (GWTG-Stroke) hospitals (n=981) contributed 479 284
      consecutive ischemic stroke or transient ischemic attack admissions. Logistic
      regression models were used to determine patient and hospital characteristics
      associated with lipid testing. RESULTS: Frequency of LDL measurement increased
      from 54.3% in 2003 to 81.9% in 2008 (P<0.001), the adjusted OR for LDL
      measurement was 1.23 per additional calendar year (95% CI, 1.18 to 1.29;
      P<0.001). The frequency of LDL measurement also increased with longer hospital
      program participation; the adjusted OR was 1.17 per additional year of GWTG
      Stroke participation (95% CI, 1.12 to 1.23; P<0.001). LDL measurement was lower
      in women, nonsmokers, those with atrial fibrillation, those with a history of
      stroke or transient ischemic attack, and in those with transient ischemic attack
      (versus ischemic stroke; all P<0.001). LDL >or=100 mg/dL was seen in 52.1% of
      those tested, including in 35.5% of patients already prescribed lipid-lowering
      therapy before admission. CONCLUSIONS: Rates of LDL measurement in hospitalized
      patients with ischemic stroke and transient ischemic attack have improved
      dramatically in this large quality improvement program, although disparities in
      testing still exist. Testing frequently revealed an LDL level that could prompt a
      change in clinical management.

PMID- 20035073
TI  - Stroke-induced immunodepression is a marker of severe brain damage.

PMID- 20035074
TI  - Ethnic influences on neurovascular coupling: a pilot study in whites and Asians.
AB  - BACKGROUND AND PURPOSE: An ethnic extraintracranial difference in atherosclerosis
      has been well reported, whereas the potential mechanism remains unclear. We aimed
      to investigate neurovascular coupling in healthy whites and Asians. METHODS:
      Twenty volunteers of each ethnicity were recruited to perform a functional
      transcranial Doppler examination with standardized checkerboard patterns as
      visual stimulation (3 x 4, 6 x 8, and 12 x 16 checks subtending a visual field
      section of 18 degrees x 24 degrees , flicker rate 1 Hz). Hemodynamic responses in
      both posterior cerebral arteries were evaluated with a control system approach.
      RESULTS: The rate time, that is, the initial speed of flow velocity adaptation,
      was significantly lower in Asians leading to an approximately 2-second delayed
      hemodynamic adaptation. The other hemodynamic parameters and the dependency of
      hemodynamic responses in regard to the complexity degree of the stimulus were
      similar between groups. CONCLUSIONS: The constellation suggests a greater initial
      mismatch between functionally increased metabolic demand of neurons and adjusted
      cerebral blood flow in Asians.

PMID- 20035075
TI  - Need to clarify Thrombolysis In Myocardial Ischemia (TIMI) scale scoring method
      in the Penumbra Pivotal Stroke Trial.

PMID- 20035076
TI  - Evaluation of the medtronic exponent self-expanding carotid stent system with the
      medtronic guardwire temporary occlusion and aspiration system in the treatment of
      carotid stenosis: combined from the MAVErIC (Medtronic AVE Self-expanding CaRotid
      Stent System with distal protection In the treatment of Carotid stenosis) I and
      MAVErIC II trials.
AB  - BACKGROUND AND PURPOSE: Embolic protection devices and improved stent technology
      have advanced the endovascular treatment of carotid artery disease. A combined
      analysis was performed of the MAVErIC (Medtronic AVE Self-expanding CaRotid Stent
      System with distal protection) I and II trials to evaluate the safety and
      feasibility of this system among patients at high risk for surgical
      endarterectomy. METHODS: Four hundred ninety-eight patients were enrolled in the
      MAVErIC I (99 patients) and MAVErIC II (399 patients) studies from June 2001 to
      October 2004. The results were pooled for statistical analysis of a common
      primary end point, the 365-day rate of major adverse events. Clinical follow-up
      took place at 30 days, 6 months, and 365 days postprocedure. RESULTS: The 365-day
      major adverse event rate, defined as death, stroke, or myocardial infarction
      within 30 days, and death, ipsilateral stroke, or myocardial infarction from days
      31 to 365 was 12.5%. The incidence of neurological death through 365 days was
      1.1%. The 30-day major adverse event rate was 5.4%. Subgroup analyses showed no
      notable differences in the 365-day major adverse event rate for symptomatic
      patients compared with asymptomatic patients. CONCLUSIONS: Treatment of carotid
      artery disease with carotid artery stenting with a self-expanding stent and
      distal embolic protection results in a low 30-day adverse event rate, including
      the occurrence of stroke in patients at high risk for carotid endarterectomy.

PMID- 20035077
TI  - Bone marrow-derived progenitor cells in cerebral autosomal dominant arteriopathy
      with subcortical infarcts and leukoencephalopathy.
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is an inherited disease due to
      cerebral microangiopathy presenting with variable pictures, including stroke,
      progressive cognitive impairment, and disability. Mechanisms leading from vessel
      structural changes to parenchymal damage and eventually to clinical expression
      are not fully understood. Among pathogenic processes, endothelial dysfunction has
      been hypothesized. Endothelial progenitor cells and circulating progenitor cells
      (CPCs) derived from bone marrow participate in endothelium structure and function
      maintenance and contribute to ischemic area revascularization. No data are
      available about these cells in CADASIL. Our objective in this study was to
      evaluate endothelial progenitor cells and CPCs role in CADASIL. METHODS: Twenty
      nine patients with CADASIL and 29 sex- and age-matched control subjects were
      enrolled. Cells were measured in peripheral blood using flow cytometry.
      Endothelial progenitor cells were defined as positive for CD34/KDR, CD133/KDR,
      and CD34/CD133/KDR; and CPCs as positive for CD34, CD133, and CD34/CD133.
      RESULTS: Endothelial progenitor cells were significantly lower in patients with
      CADASIL than in control subjects (CD34/KDR: 0.05 versus 0.1 cells/microL,
      P=0.005; CD133/KDR: 0.07 versus 0.1 cells/microL, P=0.006; CD34/CD133/KDR: 0.05
      versus 0.1 cells/microL, P=0.001). The difference remained significant after
      adjusting for age, sex, and statin use. CPCs were not significantly lower in
      CADASIL, but patients with stroke or dementia had significantly reduced CPC
      levels than patients without (CD34: 1.68 versus 2.95 cells/microL, P=0.007;
      CD133: 1.40 versus 2.82 cells/microL, P=0.004; CD34/CD133: 1.44 versus 2.75
      cells/microL, P=0.004). CPC levels significantly correlated with cognitive and
      motor performance measures. CONCLUSIONS: We have documented an association
      between endothelial progenitor cells and CPCs and CADASIL, extending previous
      data about the presence of endothelial dysfunction in this disease and its
      potential role in modulating phenotype.

PMID- 20035079
TI  - Subclinical cerebrovascular disease and cognitive decline.

PMID- 20035078
TI  - Blood-brain barrier disruption in humans is independently associated with
      increased matrix metalloproteinase-9.
AB  - BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMP) may play a role in blood
      brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma
      concentrations of MMP-9 are associated with a marker of BBB disruption in
      patients evaluated for acute stroke. METHODS: Patients underwent MRI on
      presentation and approximately 24 hours later. The MRI marker, termed
      hyperintense acute reperfusion injury marker (HARM), is gadolinium enhancement of
      cerebrospinal fluid on fluid-attenuated inversion recovery MRI. Plasma MMP-9 and
      tissue inhibitor of matrix metalloproteinase-1 were measured by enzyme-linked
      immunosorbent assay. Logistic regression models tested for predictors of HARM on
      24-hour follow-up scans separately for MMP-9 and the ratio of MMP-9 to TIMP-1.
      RESULTS: For the 41 patients enrolled, diagnoses were: acute ischemic
      cerebrovascular syndrome, 33 (80.6%); intracerebral hemorrhage, 6 (14.6%); stroke
      mimic, 1 (2.4%); and no stroke, 1 (2.4%). HARM was present in 17 (41.5%)
      patients. In model 1, HARM was associated with baseline plasma MMP-9
      concentration (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.001-1.019;
      P=0.033). In model 2, HARM was associated with the ratio of MMP-9 to tissue
      inhibitor of matrix metalloproteinase-1 (OR, 4.94; 95% CI, 1.27-19.14; P=0.021).
      CONCLUSIONS: Baseline MMP-9 was a significant predictor of HARM at 24-hour follow
      up, supporting the hypothesis that MMP-9 is associated with BBB disruption. If
      the association between MMP-9 and BBB disruption is confirmed in future studies,
      HARM may be a useful imaging marker to evaluate MMP-9 inhibition in ischemic
      stroke and other populations with BBB disruption.

PMID- 20035080
TI  - Phosphorylation of the F(1)F(o) ATP synthase beta subunit: functional and
      structural consequences assessed in a model system.
AB  - RATIONALE: We previously discovered several phosphorylations to the beta subunit
      of the mitochondrial F(1)F(o) ATP synthase complex in isolated rabbit myocytes on
      adenosine treatment, an agent that induces cardioprotection. The role of these
      phosphorylations is unknown. OBJECTIVE: The present study focuses on the
      functional consequences of phosphorylation of the ATP synthase complex beta
      subunit by generating nonphosphorylatable and phosphomimetic analogs in a model
      system, Saccharomyces cerevisiae. METHODS AND RESULTS: The 4 amino acid residues
      with homology in yeast (T58, S213, T262, and T318) were studied with respect to
      growth, complex and supercomplex formation, and enzymatic activity (ATPase rate).
      The most striking mutant was the T262 site, for which the phosphomimetic (T262E)
      abolished activity, whereas the nonphosphorylatable strain (T262A) had an ATPase
      rate equivalent to wild type. Although T262E, like all of the beta subunit
      mutants, was able to form the intact complex (F(1)F(o)), this strain lacked a
      free F(1) component found in wild-type and had a corresponding increase of lower
      molecular-weight forms of the protein, indicating an assembly/stability defect.
      In addition, the ATPase activity was reduced but not abolished with the
      phosphomimetic mutation at T58, a site that altered the formation/maintenance of
      dimers of the F(1)F(o) ATP synthase complex. CONCLUSIONS: Taken together, these
      data show that pseudophosphorylation of specific amino acid residues can have
      separate and distinctive effects on the F(1)F(o) ATP synthase complex, suggesting
      the possibility that several of the phosphorylations observed in the rabbit heart
      can have structural and functional consequences to the F(1)F(o) ATP synthase
      complex.

PMID- 20035081
TI  - The C terminus of cardiac troponin I stabilizes the Ca2+-activated state of
      tropomyosin on actin filaments.
AB  - RATIONALE: Ca(2+) control of troponin-tropomyosin position on actin regulates
      cardiac muscle contraction. The inhibitory subunit of troponin, cardiac troponin
      (cTn)I is primarily responsible for maintaining a tropomyosin conformation that
      prevents crossbridge cycling. Despite extensive characterization of cTnI, the
      precise role of its C-terminal domain (residues 193 to 210) is unclear. Mutations
      within this region are associated with restrictive cardiomyopathy, and C-terminal
      deletion of cTnI, in some species, has been associated with myocardial stunning.
      OBJECTIVE: We sought to investigate the effect of a cTnI deletion-removal of 17
      amino acids from the C terminus- on the structure of troponin-regulated
      tropomyosin bound to actin. METHODS AND RESULTS: A truncated form of human cTnI
      (cTnI(1-192)) was expressed and reconstituted with troponin C and troponin T to
      form a mutant troponin. Using electron microscopy and 3D image reconstruction, we
      show that the mutant troponin perturbs the positional equilibrium dynamics of
      tropomyosin in the presence of Ca(2+). Specifically, it biases tropomyosin
      position toward an "enhanced C-state" that exposes more of the myosin-binding
      site on actin than found with wild-type troponin. CONCLUSIONS: In addition to its
      well-established role of promoting the so-called "blocked-state" or "B-state,"
      cTnI participates in proper stabilization of tropomyosin in the "Ca(2+)-activated
      state" or "C-state." The last 17 amino acids perform this stabilizing role. The
      data are consistent with a "fly-casting" model in which the mobile C terminus of
      cTnI ensures proper conformational switching of troponin-tropomyosin. Loss of
      actin-sensing function within this domain, by pathological proteolysis or
      cardiomyopathic mutation, may be sufficient to perturb tropomyosin conformation.

PMID- 20035082
TI  - Critical role for leukocyte hypoxia inducible factor-1alpha expression in post
      myocardial infarction left ventricular remodeling.
AB  - RATIONALE: Hypoxia inducible factor (HIF)-1alpha is a transcription factor
      stabilized by hypoxia. It regulates cytokines involved in the inflammatory
      response after ischemia and affects white blood cell (WBCs) function. The effect
      of HIF-1alpha on WBC function and inflammation following myocardial infarction
      (MI) is unknown. OBJECTIVE: We assessed peritoneal and myocardial inflammation in
      the setting of low WBC HIF-1alpha expression through bone marrow transplantation
      of hematopoietic stem cells transfected with scramble or HIF-1alpha small
      interfering (si)RNA. METHODS AND RESULTS: Rosa hematopoietic stem cells (lin(-),
      cKit(+)) were transfected with a green fluorescent protein (GFP) reporter
      lentivirus encoding a siRNA to HIF-1alpha or scramble. Irradiated 6- to 8-week
      old C57/BL6J mice received 50 000 GFP(+) HIF-1alpha or scramble siRNA-transfected
      hematopoietic stem cells. Peritonitis or myocardial infarction via left anterior
      descending coronary artery ligation was induced 6 weeks after bone marrow
      transplantation. In the peritonitis model, HIF-1alpha siRNA group exhibited a
      significant decrease in neutrophil and monocyte entry to the peritoneum compared
      to scramble mice. Similarly neutrophil infiltration into the infarct zone was
      decreased in the HIF-1alpha siRNA group. No difference of myocardial infarct size
      was observed between groups. Interestingly, the ejection fraction were similar in
      both groups at baseline and 3 days post-MI but increased significantly in the HIF
      1alpha siRNA group compared to control beginning 7 days after MI. Gene array
      studies demonstrated that downregulation of WBC HIF-1alpha was associated with
      decreased WBC CCR1, -2, and -4 expression. Chemotaxis assay results confirmed
      that decreased monocyte migration induced by downregulation of HIF-1alpha was
      partially reversed by overexpression of CCR2. CONCLUSIONS: Downregulation of
      leukocyte HIF-1alpha expression resulted in decreased recruitment of WBC to the
      sites of inflammation and improvement in cardiac function following MI.
      Downregulation of HIF-1alpha suppressed WBC cytokine receptors CCR1, -2, and -4,
      which are necessary for WBC mobilization and recruitment to inflammatory
      cytokines following MI. The effects of downregulation of leukocyte HIF-1alpha on
      WBC migration are attributable, at least in part, to the decreased CCR2
      expression. These results demonstrate that WBC infiltration into the newly
      injured myocardium plays a significant role in left ventricular remodeling, but
      not infarct size.

PMID- 20035085
TI  - Circulation journal: a cloud over the hill.

PMID- 20035086
TI  - Noncontact mapping: utility and limitations.

PMID- 20035084
TI  - Role of mesodermal FGF8 and FGF10 overlaps in the development of the arterial
      pole of the heart and pharyngeal arch arteries.
AB  - RATIONALE: The genes encoding fibroblast growth factor (FGF) 8 and 10 are
      expressed in the anterior part of the second heart field that constitutes a
      population of cardiac progenitor cells contributing to the arterial pole of the
      heart. Previous studies of hypomorphic and conditional Fgf8 mutants show
      disrupted outflow tract (OFT) and right ventricle (RV) development, whereas Fgf10
      mutants do not have detectable OFT defects. OBJECTIVES: Our aim was to
      investigate functional overlap between Fgf8 and Fgf10 during formation of the
      arterial pole. METHODS AND RESULTS: We generated mesodermal Fgf8; Fgf10 compound
      mutants with MesP1Cre. The OFT/RV morphology in these mutants was affected with
      variable penetrance; however, the incidence of embryos with severely affected
      OFT/RV morphology was significantly increased in response to decreasing Fgf8 and
      Fgf10 gene dosage. Fgf8 expression in the pharyngeal arch ectoderm is important
      for development of the pharyngeal arch arteries and their derivatives. We now
      show that Fgf8 deletion in the mesoderm alone leads to pharyngeal arch artery
      phenotypes and that these vascular phenotypes are exacerbated by loss of Fgf10
      function in the mesodermal core of the arches. CONCLUSIONS: These results show
      functional overlap of FGF8 and FGF10 signaling from second heart field mesoderm
      during development of the OFT/RV, and from pharyngeal arch mesoderm during
      pharyngeal arch artery formation, highlighting the sensitivity of these key
      aspects of cardiovascular development to FGF dosage.

PMID- 20035087
TI  - Japan expects decrements in both the incidence and mortality of acute myocardial
      infarction in the modern era: likely or just a dream?

PMID- 20035083
TI  - Insufficient deactivation of the protein tyrosine kinase lck amplifies T-cell
      responsiveness in acute coronary syndrome.
AB  - RATIONALE: In the vulnerable atherosclerotic plaque, T cells may destabilize the
      tissue structure through direct cell-injurious effector functions. T cells
      transmit environmental signals, such as recognition of antigen, into cellular
      responses through regulated phosphorylation of cytoplasmic proteins, with the Src
      family kinase Lck (lymphocyte-specific protein tyrosine kinase) in critical
      membrane-proximal position of the T-cell receptor (TCR) signaling cascade. The
      balance between protein phosphorylation and dephosphorylation defines the signal
      transduction threshold and determines appropriate T-cell responses. OBJECTIVE: We
      have examined whether abnormal calibration of intracellular signaling pathways
      renders acute coronary syndrome (ACS) patients susceptible to disproportionate T
      cell responses. METHODS AND RESULTS: Intracellular signaling cascades were
      quantified in CD4 T cells from ACS patients and control individuals after
      stimulation with major histocompatibility complex class II-superantigen
      complexes. ACS T cells mobilized more intracellular calcium and accumulated
      higher levels of phosphotyrosine than control T cells. Proximal steps in TCR
      signaling, such as recruitment of ZAP-70 and clustering of TCR complexes in the
      immune synapse, were abnormally enhanced in ACS T cells. Acceleration of the
      signaling cascade derived from a proximal defect in ACS T cells, which failed to
      phosphorylate Lck at Tyr505, extending activation of the Src kinase.
      Abnormalities in TCR signaling did not correlate with systemic inflammation as
      measured by C-reactive protein. CONCLUSIONS: An intrinsic abnormality in the
      signaling machinery of ACS T cells resulting in the accumulation of active Lck
      lowers the TCR threshold and renders lymphocytes hyperreactive and capable of
      unwanted immune responses.

PMID- 20035088
TI  - Role of endostatin in cardiovascular remodeling.

PMID- 20035089
TI  - Antenatal glucocorticoid therapy for fetal heart development.

PMID- 20035090
TI  - Novel in vivo tool to evaluate autophagic activity in the heart.

PMID- 20035091
TI  - Optimal cutoff points of waist circumference for the criteria of abdominal
      obesity: comparison with the criteria of the International Diabetes Federation.

PMID- 20035093
TI  - Multiple immunofluorescence labeling in tissue sections.

PMID- 20035094
TI  - Damage control surgery and open abdominal management: recent advances and our
      approach.
AB  - The concept of damage control and improved understanding of the pathophysiology
      of abdominal compartment syndrome (ACS) have been proven to be great advances in
      the management of both traumatic and nontraumatic surgical conditions. The
      practice of damage control surgery includes 3 components: 1) abbreviated
      resuscitative surgery for rapid control of hemorrhage and abdominal contamination
      by gastrointestinal contents, followed by temporary abdominal wall closure for
      planned reoperation and prevention of ACS; 2) restoration of physiologic
      function, including rewarming and correction of coagulopathy and hemodynamic
      stabilization in the intensive care unit; and 3) re-exploration for the
      definitive management of injuries and abdominal wall closure. Although this new
      approach can decrease the mortality rate of patients with severe physiological
      derangement, the establishment of clearly defined indications is necessary. For
      patients who require damage control surgery, interventional radiology should be
      integrated into the strategy for achieving hemostasis. Angiographic evaluation
      and embolization should be considered immediately after initial operation,
      especially for patients with combined intraperitoneal and retroperitoneal
      hemorrhage, severe hepatic injury, or ongoing hemorrhage after damage control
      surgery. In many patients who require conventional open abdominal management
      following damage control surgery or decompressive laparotomy for ACS, the
      granulating abdominal contents are covered with only a skin graft, which is
      associated with a risk of enterocutaneous fistula. These patients will ultimately
      require complex abdominal wall reconstruction at a later stage. We have performed
      early fascial closure using an anterior rectus abdominis sheath turnover flap
      method. This technique may reduce the need for skin grafting and subsequent
      reconstruction and can be considered as an alternative method for the early
      management of patients with open abdomen.

PMID- 20035095
TI  - Detection of arrhythmogenic substrates in prior myocardial infarction patients
      with complete right bundle branch block QRS using wavelet-transformed ECG.
AB  - BACKGROUND: It is important to follow up patients surviving acute myocardial
      infarction (MI), to detect the presence of any life-threatening arrhythmias.
      Various non-invasive examinations, such as signal-averaged ECG (SAECG), have been
      reported to predict the fatal ventricular tachycardia (VT); however, these
      conventional methods have limitations in detecting VT occurring in patients with
      complete right bundle branch block (CRBBB) QRS. Wavelet transform has been
      increasingly reported as a superior time-frequency analysis on the surface ECG in
      detecting abnormal high-frequency components (HFCs), thus suggesting abnormal
      myocardial conductions; however, it remains unclear whether wavelet-transformed
      ECG (WTECG) is useful in patients with CRBBB. OBJECTIVE: The purpose of this
      study is to assess the predictive value of WTECG for detecting arrhythmogenic
      substrates in MI patients with CRBBB. METHODS: Both the WTECG and SAECG were
      evaluated in 22 subjects with CRBBB, including 10 subjects without cardiovascular
      diseases (control group), 7 prior MI patients without VT (Non-VT group), and 5
      prior MI patients with sustained VT (VT group). A 12-lead ECG (10 kHz sampling)
      was recorded and the representative QRS complex (300 ms) was transformed at a
      frequency range of 40-280 Hz using the Gabor function as the analyzing wavelet.
      In the power curve along a time course, the percentages of the peak power values
      at each frequency (60, 80, 120, 150, and 200 Hz) in the corresponding power
      values at 40 Hz (P60/40, P80/40, P120/40, P150/40, and P200/40, respectively)
      were calculated. 'The power percentages (P120/40, P150/40, or P200/40) > or =50%'
      was defined as an abnormal HFC (AHFC), and the number of the leads in which an
      AHFC was detected (NL-AHFC) of 8 leads (I, aV(F), V1-V6) was counted for
      comparison of the two MI groups. RESULTS: There was no significant difference
      among the three groups in the SAECG recording. The power percentages of HFCs
      (P120/40, P150/40, and P200/40) in Non-VT group were significantly higher than
      those in control group (48.2 +/- 36.5 vs. 30.6 +/- 7.7, P<0.001; 47.8 +/- 35.5
      vs. 26.9 +/- 7.1, P<0.001; 47.3 +/- 39.4 vs. 24.9 +/- 7.6, P<0.001;
      respectively). NL-AHFC (P150/40) in VT group significantly increased more than in
      Non-VT group (3.2 +/- 0.4 vs. 1.4 +/- 0.8, P=0.001). When 'NL-AHFC (P150/40) > or
      =3' was defined as abnormal, the sensitivity, specificity, positive and negative
      predictive values for detection of VT in MI patients with CRBBB was 100, 85.7,
      83.3, and 100%, respectively. CONCLUSION: WTECG might be a novel non-invasive
      method to detect arrhythmogenic substrates in MI patients with CRBBB.

PMID- 20035096
TI  - Clinical features of antinuclear antibody-positive patients with atopic
      dermatitis.
AB  - Twenty to thirty percent of patients with atopic dermatitis (AD) are positive for
      antinuclear antibodies (ANAs). In this study we investigated the prevalence of
      ANA in 100 patients with AD and examined the difference between ANA-positive
      (ANA+) and ANA-negative (ANA(-)) patients with AD. ANAs were identified with
      indirect immunofluorescence on Hep-2 cells. Nineteen patients (19%) with AD were
      found to be positive for ANAs at titers ranging from 1 : 40 to 1 : 640. The rate
      of ANA positivity in male patients (20.4%) was higher than that in female
      patients (17.6%). The rate of ANA positivity differed significantly between
      patients with AD and healthy control subjects (p=0.0001, odds ratio: 2.8). There
      was also a relationship between ANA+ AD and photosensitivity in male subjects
      (p=0.0346). The ANA+ patients with AD showed higher levels of cedar pollen
      specific IgE than did ANA(-) patients (p=0.0232). In ANA+ patients disease
      severity was correlated with basophil counts (r=0.513, p=0.0344) and serum LDH
      levels (r=0.741, p=0.0056). The results indicate that patients with AD who are
      positive for ANA are a subpopulation of patients with AD.

PMID- 20035097
TI  - Successful management of a symptomatic splenic artery aneurysm with transcatheter
      embolization.
AB  - We describe a symptomatic splenic artery aneurysm (SAA) with occasional left
      sided abdominal pain which was successfully treated with transcatheter
      embolization. A 65-year-old man was referred to a nearby clinic because of left
      shoulder and abdominal pain developing the day after blunt trauma to the shoulder
      and abdomen. Radiography revealed no fracture, and the patient went home. He
      stopped working for 7 months. Left-sided abdominal pain then developed several
      times after strenuous physical labor, and the patient was referred to a nearby
      hospital. The patient had a history of asthma and untreated hypertension; the use
      of iodinated contrast material was therefore avoided. Unenhanced computed
      tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed a
      hematoma in the splenic hilum. The patient was referred to Nippon Medical School
      Hospital. His neurologic status was stable. Unenhanced CT of the abdomen at a
      nearby hospital revealed a low-density area in the splenic hilum. Fat-suppressed,
      T1-weighted images showed a hyperintense lesion adjacent to the splenic hilum.
      Fat-suppressed, T2-weighted images showed a dark hemosiderin rim, a bright ring,
      and an intermediate central core, which indicated a recurrent chronic hematoma in
      the abdomen. Dynamic contrast-enhanced MRI revealed a small hyperenhanced lesion
      adjacent to the hematoma, which appeared to be an SAA. After an injection of
      corticosteroids, selective splenic arteriography was performed. The splenic
      artery was catheterized via a right femoral approach. Arteriography showed an
      SAA, 1 cm in diameter with extravasation of contrast material. The neck of the
      SAA was catheterized with a microcatheter, and coils were placed successfully
      into the SAA to prevent recurrent bleeding. Postembolization angiography showed
      total occlusion of the SAA. The patient was discharged 7 days after embolization
      and has since resumed normal activities, with no residual symptoms.

PMID- 20035098
TI  - Two cases of restrictive cardiomyopathy in children.
AB  - A 3-year-old girl was diagnosed with restrictive cardiomyopathy (RCM) after
      showing symptoms of heart failure, and a 6-year-old boy was found to have RCM
      after abnormal electrocardiographic findings were seen during school-based heart
      disease screening. Both had typical clinical features of the disease. Plasma
      levels of brain natriuretic peptide increased significantly in both patients,
      allowing us to distinguish this disease from constrictive pericarditis which has
      similar clinical and hemodynamic features. The early diastolic mitral annular
      velocity recorded by tissue Doppler echocardiography was also useful to
      discriminate RCM from constrictive pericarditis. The former case successfully
      received heart transplantation, but the latter case died suddenly prior to
      receiving a heart transplant. The plasma level of brain natriuretic peptide and
      tissue Doppler echocardiography helped us to diagnose this disease earlier and
      follow it more carefully, which has important implications in optimal treatment
      and improved prognosis of RCM in children.

PMID- 20035099
TI  - Laparoscopic unroofing of a large pseudocyst of the spleen: report of a case.
AB  - The treatment of splenic cysts remains controversial. A 25-year-old Japanese
      woman with a 10-cm-long abdominal mass in the left upper quadrant of the abdomen
      complained of mild, dull pain. A huge splenic cyst was confirmed on computed
      tomography and magnetic resonance imaging. The cyst wall was adherent to the
      splenic parenchyma to approximately 30% of its maximum diameter, calculated with
      magnetic resonance imaging. Laparoscopic unroofing of the cyst was performed.
      After the great omentum adhering to the cystic wall of the spleen was dissected,
      branches from the splenic hilar vessels were clipped. Histological examination of
      the cyst revealed pseudocyst of the spleen. The postoperative course was
      uneventful. Laparoscopic unroofing is a safe surgical procedure for patients with
      symptomatic pseudocyst of the spleen.

PMID- 20035103
TI  - Cell injuries of the blood-air barrier in acute lung injury caused by
      perfluoroisobutylene exposure.
AB  - OBJECTIVES: To investigate the complete process of cell injuries in the blood-air
      barrier after perfluoroisobutylene (PFIB) exposure. METHODS: Rats were exposed to
      PFIB (140 mg/m(3)) for 5 min. The pathological changes were evaluated by lung wet
      to-dry weight ratio, total protein concentration of bronchoalveolar lavage fluid
      and HE stain. Ultrastructural changes were observed by transmission electron
      microscope. Apoptosis was detected by in situ apoptosis detection. Changes of
      actin in the lung tissue were evaluated by western blot assay. RESULTS: No
      significant pulmonary edema or increased permeability was observed within the
      first 4 h, post PFIB exposure. However, inflammatory cell infiltration and
      alveolar wall thickening were observed from 2 h. Destruction of the alveoli
      constitution integrity, edema and protein leakage were observed at 8 h. The
      injuries culminated at 24 h and then recovered gradually. The ultrastructural
      injuries of alveolar type I epithelial cells, alveolar type II epithelial cells
      and pulmonary microvascular endothelial cells were observed at 30 min post PFIB
      exposure. Some injuries were similar to apoptosis. Compared with control, more
      serious injuries were observed in PFIB-exposed rats after 30 min. At 8 h, some
      signs of cell necrosis were observed. The injuries culminated at 24 h and then
      ameliorated. The number of apoptotic cells abnormally increased at 30 min post
      PFIB exposure, the maximum appeared at 24 h, and then ameliorated gradually.
      Western blot analysis revealed that the level of actin in the lung showed no
      significant changes within the first 4 h post PFIB exposure. However, it
      decreased at 8 h, reached a nadir at 24 h, and then recovered gradually.
      CONCLUSIONS: The pathological processes were in progress persistently post PFIB
      exposure. The early injuries probably were the result of the direct attack of
      PFIB and the advanced injuries probably arose from the inflammatory reaction
      induced by PFIB.

PMID- 20035104
TI  - Localization of five steroidogenic enzyme mRNAs in Japanese black bear (Ursus
      thibetanus japonicus) testes during the mating season by in situ hybridization.
AB  - The Japanese black bear (Ursus thibetanus japonicus) is a typical seasonal
      breeder that has a mating season in early summer. Spermatogenesis and testicular
      steroidogenesis are known to develop and regress annually; however, its molecular
      mechanism has not yet been investigated. In the present study, we clarified the
      mRNA sequence of 5 steroidogenic enzymes (P450scc, 3betaHSD, P450c17, 17betaHSD3
      and P450arom) using RT-PCR and RACE methods and the localization of these gene
      expressions in the bear testis using an in situ hybridization technique. The
      amino acid sequence deduced from each mRNA sequence had high homology with the
      corresponding sequences of other species and possessed a motif typical of the
      P450 family or short chain alcohol dehydrogenase family. Expression of P450scc,
      3betaHSD and P450c17 mRNA in interstitial tissue indicated that conversion from
      cholesterol to androstenedione occurs in Leydig cells. On the other hand, the
      mRNA of 17betaHSD3, which plays a central role in synthesizing testosterone, was
      detected not only in the interstitium but also inside the seminiferous tubules,
      along the basement membrane. P450arom mRNAs were distributed in the seminiferous
      tubules. These results suggest the possibility of testosterone and estradiol
      17beta synthesis inside the seminiferous tubules in the bear testis. We expect
      that the results of this study will be useful for further investigation of the
      molecular mechanism of steroidogenic seasonality in the bear testis.

PMID- 20035105
TI  - Expression and localization of cFLIP, an anti-apoptotic factor, in the bovine
      corpus luteum.
AB  - The objective of the present study was to investigate the potential mechanisms
      regulating cellular FLICE-like inhibitory protein (cFLIP), an anti-apoptotic
      factor, in the bovine corpus luteum (CL). Expression of cFLIP mRNA was highest at
      the developing stage and then decreased significantly during the mid, late and
      regressed stages (P<0.05). Western blot analysis revealed that expression of the
      long isoform of cFLIP (cFLIP(L)) protein was high during the early and developing
      luteal stages, remained steady during the mid and late luteal stages and then
      decreased significantly (P<0.05) by the regressed stage. However, the expression
      levels of the short isoform of cFLIP (cFLIP(S)) remained low during the early,
      developing and mid luteal stages. Immunostaining of cFLIP was strongest in the
      cytoplasm of luteal and non-luteal cells, including endothelial and immune cells,
      remained high during the early, developing and mid luteal stages and then
      decreased significantly (P<0.05) in the late and regressed luteal stages.
      Immunostaining of cFLIP was observed only in macrophage-like cells in the
      regressing CL. However, cultured mid luteal cells had a higher percentage of
      cFLIP-positive cells and a lower percentage of TUNEL-positive cells than luteal
      cells treated with tumor necrosis factor alpha (TNF)/interferon gamma (IFNG;
      P<0.01). These results indicate downregulation of cFLIP during structural luteal
      regression, suggesting that cFLIP plays a survival role in the bovine CL.

PMID- 20035106
TI  - Profiles of circulating steroid hormones, gonadotropins, immunoreactive inhibin
      and prolactin during pregnancy in goats and immunolocalization of inhibin
      subunits, steroidogenic enzymes and prolactin in the corpus luteum and placenta.
AB  - The current study was performed to follow up the circulating hormonal changes and
      to correlate the findings with the physiological activity of the corpus luteum
      (CL) and placenta during pregnancy in goats. Blood samples were collected weekly
      from five goats during pregnancy for measuring steroid and protein hormones. A
      gradual increase was observed in immunoreactive (ir-) inhibin, with maximal
      levels at the 17th week. The plasma concentrations of estradiol and prolactin
      (PRL) showed nearly similar patterns during pregnancy, where they declined to
      basal levels during the first 4 weeks post-breeding and then increased
      significantly, with the maximal concentration during late pregnancy. The plasma
      FSH and LH concentrations were maintained at basal levels throughout the
      gestation period. The plasma progesterone concentration abruptly increased in the
      first week post-breeding and remained at high values throughout the pregnancy
      period. Immunohistochemical localization of inhibin alpha, beta(A), beta(B) and
      steroidogenic enzymes cytochrome P450 aromatase, 3alpha-hydroxysteroid
      dehydrogenase (3betaHSD), cytochrome 17alpha-hydroxylase P450 and cholesterol
      side-chain cleavage cytochrome P450 in the cyclic and pregnant goat CL revealed
      positive immunoreactivity without affinity differences between the luteal and
      pregnancy stages. The placental syncytiotrophoblasts also showed positive
      staining, except for inhibin beta(A) and 3betaHSD. The giant binucleate cells of
      the placenta showed positive immunoreactions to PRL. These results suggest that
      the high concentrations of ir-inhibin, estradiol and PRL during late pregnancy
      are of placental origin and that the placenta may have a vital role in the
      maintenance of pregnancy, regulation of mammary growth and preparation for
      kidding and lactation in goats.

PMID- 20035107
TI  - Expression of VEGF and its receptors in the bovine endometrium throughout the
      estrous cycle: effects of VEGF on prostaglandin production in endometrial cells.
AB  - Vascular endothelial growth factor (VEGF) is a well known angiogenic factor that
      has been suggested to play some physiological roles in reproductive organs. To
      clarify whether VEGF is involved in regulating bovine endometrial function
      locally, in experiment 1, we determined the expression of VEGF, VEGF receptor
      (VEGFR) 1 and VEGFR2 throughout the estrous cycle in endometrial tissues.
      Endometrial tissue was collected at estrus (Day 0), the early I (Days 2-3), early
      II (Days 5-6), mid (Days 8-12) and late luteal stages (Days 15-17) and the
      follicular stage (Days 19-21). RT-PCR and Western blotting analysis revealed that
      VEGF mRNA expression at estrus was higher than at the early I, early II and late
      luteal stages (P<0.05), whereas VEGF protein content was greatest at the early I
      luteal stage and decreased thereafter. VEGFR1 mRNA expression was lower at estrus
      and at the early I and early II luteal stages than at the other stages, whereas
      VEGFR1 protein expression did not change significantly throughout the estrous
      cycle (P<0.05). VEGFR2 mRNA expression was higher at the mid and late luteal
      stages than at the early I and early II luteal stages, and VEGFR2 protein was
      higher at the mid and late luteal stages than at estrus (P<0.05). In experiment
      2, to determine the effect of VEGF on prostaglandin (PG) F2alpha and PGE2
      production by endometrial cells, cultured endometrial epithelial and stromal
      cells were exposed to VEGF (0, 5, 50, 100 and 200 ng/ml) for 24 h. VEGF (200
      ng/ml) stimulated PGF2alpha production by stromal cells (P<0.05), but not PGE2
      production. VEGF did not affect PG production by endometrial epithelial cells.
      The overall results suggest that VEGF and its receptors are regulated throughout
      the estrous cycle and that VEGF participates in the local regulation of bovine
      endometrial function by a selective modulation of PGF2alpha production in stromal
      cells in an auto- and/or paracrine manner.

PMID- 20035108
TI  - A clinical study of anestrus buffaloes in southern Nepal.
AB  - Anestrus is one of the most important reproductive disorders in dairy buffaloes.
      The clinical features of anestrus in buffaloes, however, have not been well
      described. The objectives of this study were to describe the causes of anestrus
      in buffaloes and their reproductive performance after treatment under field
      conditions in southern Nepal. Of 135 anestrus buffalo cows, 61.4% had true
      anestrus with ovarian dysfunction and 33.3% had silent ovulation. In 111 buffalo
      heifers, 76.6% were in true anestrus and 18.9% had silent ovulation. The duration
      of anestrus after calving was longer than 6 months in 83% of buffalo cows and
      61.5% of the buffalo cows had durations longer than 10 months. The interval
      between the last breeding and diagnosis of anestrus was more than 5 months in
      67.4% of cows and heifers. Treatment of anestrus with prostaglandin F(2)alpha in
      cows and heifers with a corpus luteum resulted in higher pregnancy rates within
      one (P<0.01) and two months (P<0.05) after treatment as compared with treatment
      with a vitamin/mineral mixture. Buffalo cows and heifers with inactive ovaries
      bearing a dominant follicle were also successfully treated with gonadotropin
      releasing hormone, resulting in higher pregnancy rate within one month after
      treatment (P<0.05). In conclusion, the predominant cause of anestrus in dairy
      buffaloes in this region was true anestrus with inactive ovaries, and the
      duration of anestrus after calving as well as breeding was extremely long.
      Routine reproductive examination and adequate hormone treatment may improve the
      reproductive performance of these buffaloes.

PMID- 20035109
TI  - Viability of porcine embryos after vitrification using water-soluble pullulan
      films.
AB  - The efficiency of a porcine embryo vitrification method that uses water-soluble
      films of pullulan, a naturally-occurring polysaccharide polymer, was compared
      with two other types of vitrification methods using different devices and
      solutions for vitrification and warming. Blastocysts collected in vivo and
      vitrified by the conventional straw (ST), Cryotop((R)) (MVC) or pullulan film
      vitrification (PFV) methods were stored in liquid nitrogen for a certain period
      of time, after which the cryoprotective agents were removed by stepwise dilution.
      Fresh embryos were used as controls for the non-vitrification group. The
      vitrified-warmed embryos were incubated in TCM199 with 0.1 mM beta
      mercaptoethanol and 20% fetal bovine serum for 24 h at 38.5 C in humidified air
      with 5% CO(2) to evaluate their viability. The survival rate of embryos in the ST
      group (48.3%) was significantly lower than that of those in the MVC (70.7%), PFV
      (79.0%) and non-vitrification (94.4%) groups. The oxygen consumption rate after
      vitrification was significantly lower than that before vitrification in the ST
      group, but was not significantly different in the MVC and PFV groups. Both the
      oxygen consumption rates of embryos after warming and the live cell numbers in
      the ST group were lower than those in the MVC group, while they did not differ
      significantly between the PFV and MVC groups. There was a correlation between the
      oxygen consumption rate and the number of live cells in vitrified embryos after
      warming. Our results demonstrated that in vivo-derived porcine embryos could be
      vitrified using pullulan films.

PMID- 20035110
TI  - Relationship between the length of cell cycles, cleavage pattern and
      developmental competence in bovine embryos generated by in vitro fertilization or
      parthenogenesis.
AB  - This study was conducted to study the kinetics of initial cell divisions in
      relation with the cleavage patterns in viable (with the ability to develop to the
      blastocyst stage) and non-viable bovine embryos and parthenotes. The kinetics of
      in vitro development and cleavage patterns were observed by time lapse
      cinematography. The length of the first and second but not third cell cycle
      differed significantly between the viable and non-viable embryos after IVF or
      parthenogenesis. Viable embryos had significantly shorter first and second cell
      cycles than non-viable ones. The presence of fragments, protrusions and unequally
      sized blastomeres was associated with an extended one-cell stage and reduced
      ability to develop to the blastocyst stage; however, the lengths of the second
      and third cell cycles were not altered. Oocytes showing direct division from one
      cell to 3 or 4 blastomeres showed similar developmental ability and embryonic
      cell numbers to those showing normal division, although, with a high frequency of
      chromosomal abnormalities. Our results suggest that the differences in the first
      cell cycles between viable and non-viable embryos were not sperm-related, whereas
      direct cleavage of 1-cell embryos to 3 or more blastomeres and protrusion
      formation are related to sperm-driven factors. The length of the first and second
      cell cycles and the cleavage pattern should be examined simultaneously to predict
      developmental competence of embryos at early cleavage stages.

PMID- 20035111
TI  - Protective effect of quercetin on the reproductive toxicity of 4-nitrophenol in
      diesel exhaust particles on male embryonic chickens.
AB  - The 4-nitrophenol (PNP) in diesel exhaust particles (DEP) has been identified as
      a vasodilator and is a known degradation product of the insecticide parathion. In
      this study, the protective effect of quercetin, a potent oxygen free radical
      scavenger and metal chelator, against the oxidative damage of PNP on cultured
      testicular cells was studied in male embryonic chickens. Testicular cells from
      Day 18 embryos were cultured in serum-free McCoy's 5A medium and challenged with
      quercetin (1.0 microg/ml) alone or in combinations with PNP (10(-7)-10(-5) M) for
      48 h. The oxidative damage was estimated by measuring cell viability, content of
      malondialdehyde (MDA), activity of superoxide dismutase (SOD) and glutathione
      peroxidation (GSH-Px) activity. The results showed that exposure to PNP (10(-5)
      M) induced condensed nuclei, vacuolated cytoplasm and a decrease in testicular
      cell viability and spermatogonial cell number. Exposure to PNP induced lipid
      peroxidation by elevation of the content of MDA. Exposure to PNP also decreased
      GSH-Px activity and SOD activity. However, simultaneous supplementation with
      quercetin restored these parameters to the same levels as the control.
      Consequently, PNP induced oxidative stress in spermatogonial cells, and dietary
      quercetin may attenuate the reproductive toxicity of PNP to restore the
      intracellular antioxidant system in the testicular cells of embryonic chickens.

PMID- 20035112
TI  - Spacing of the embryo in the uterus is disrupted by the supine position of the
      body during the peri-implantation period in mice.
AB  - This study aimed to clarify the mechanism of the spacing of murine embryos along
      the metrial and anti-metrial (MA) axis of the uterus using our newly developed
      experimental model. The model mice were produced by keeping mice in the supine
      position from the pre-implantation to implantation period. The starting points
      and periods of restraint of the mice in the supine position were set variously
      during the peri-implantation. Then, the position of the embryo was evaluated
      morphologically. In only one group (set in the instrument from the second day of
      pregnancy, Day 2, to Day 5), strong disruption of embryo spacing along the MA
      axis was observed. On the other hand, there was little abnormality in embryo
      positioning in the groups that were treated from Day 3 to Day 5 or from Day 3 to
      Day 6. These results suggested that determination of the position of the embryo
      in the MA axis is not related to duration of the experiment (2 days or 3 days),
      but is related to the starting time-point of the experiment, at Day 2 or Day 3.
      In conclusion, the period between Days 2 and 3 is critical for determination of
      the position of the embryo along the MA axis.

PMID- 20035113
TI  - Immune recovery effects of immunopotentiator from Pantoea agglomerans 1 (IP-PA1)
      on low antibody productions in response to Salmonella enteritidis vaccine and
      sheep red blood cells in dexamethasone-treated stressed chicken models.
AB  - Considering the usefulness of the immunopotentiator from Pantoea agglomerans 1
      (IP-PA1), which is a purified lipopolysaccharide (LPS) derived from symbiotic
      gram-negative bacteria of food crops, in controlling immunosuppression in poultry
      husbandry, in this study, we examined its immune-recovery effects in
      dexamethasone-treated stressed chicken models. Three-week-old chickens daily
      administered 10 microg/kg of dexamethasone for 35 days to induce stress showed
      more whole body weight loss; relative thymic, bursal, and splenic weight losses;
      and decrease in the number of peripheral blood lymphocytes, as compared with the
      control chickens on day 35; the IP-PA1-pretreated, dexamethasone-treated chickens
      showed reduced weight losses. Five- to eight-week-old chickens administered 5
      mg/kg of dexamethasone showed excessive apoptosis of thymic and bursal
      lymphocytes 24 hr after a single dexamethasone treatment; apoptosis was inhibited
      in the IP-PA1-pretreated, dexamethasone-treated chickens. Chickens daily
      administered 10 microg/kg of dexamethasone for 35 days and injected with
      commercial Salmonella Enteritidis (SE) vaccine or sheep red blood cells (SRBC) on
      days 7 and 21 showed about 8- or 2-fold lower antibody production in response to
      SE or SRBC, respectively, as compared with the control chickens on day 35; the
      antibody production in response to SE or SRBC was increased in the IP-PA1
      pretreated, dexamethasone-treated chickens. These results indicate that IP-PA1
      exerts inhibitory effects on dexamethasone-induced immunosuppression and that it
      may be useful in controlling immunosuppression in poultry husbandry.

PMID- 20035114
TI  - Occurrence of Listeria monocytogenes in salami manufactured in the Marche Region
      (Central Italy).
AB  - The aim of the present study was to investigate the occurrence of Listeria
      monocytogenes in salami samples collected from production plants of the Marche
      Region, and to assess the end-product acceptability based on the former Italian
      regulations and European Commission (EC) Regulation No 2073/2005. Based on the
      limits specified in the former Italian regulations, the percentage of non
      acceptable samples was 34.3%, whereas based on the limits specified in EC
      Regulation N degrees 2073/2005, a lower percentage (17.1%) was seen. A similar
      trend was seen also when only the Ciauscolo salami were considered, with 45.2 and
      27.4% of non-acceptable samples, respectively. No correlations were identified
      between occurrence of L. monocytogenes and the main parameters or the
      manufacturing processes.

PMID- 20035115
TI  - Anatomical variations of the extrahepatic ducts in dogs: knowledge for surgical
      procedures.
AB  - Variations of the hepatic duct terminal were examined in 50 cadavers of mixed
      breed dogs. The hepatic duct was formed by 4 major tributaries in 70% of the dogs
      and by 3 tributaries in 30% of the dogs. The order of hepatic duct termination,
      proximal to the gallbladder, was as follows: the duct from the right medial lobe,
      then the quadrate, then the common duct from the right lateral and caudate lobes
      and finally the duct from the left lobes in most of the dogs (90%). In only 10%
      of the dogs, the duct from the quadrate lobe terminated proximal to the duct from
      the right medial lobe. The length of the cystic duct was more than 5 mm in most
      dogs (88%). This study showed anatomical variations of the extrahepatic biliary
      tree and their preoperational imaging. These results may be useful for shortening
      the operative period and provide basic information for the application of
      laparoscopic cholecystectomies.

PMID- 20035116
TI  - Cytokeratin 8/18 is a useful immunohistochemical marker for hepatocellular
      proliferative lesions in mice.
AB  - In order to clarify whether cytokeratin (CK) 8/18 is a useful immunohistochemical
      marker for hepatocellular proliferative lesions in mice, partially hepatectomized
      male ICR mice were given 0.6% piperonyl butoxide (PBO) for 8 (Experiment I) or 25
      weeks (Experiment II) after N-diethylnitrosamine (DEN) initiation treatment, and
      the livers were subjected to histological examinations on hematoxylin and eosin
      (HE) stained sections, CK8/18 immunohistochemistry and gamma-glutamyl
      transpeptidase (GGT) histochemistry. In Experiment I, the multiplicity of
      hepatocellular foci in paraffin-embedded sections which were observed in HE
      stained sections and positive for CK8/18 was 10.17 and 18.50, respectively, while
      that of hepatocellular foci in frozen sections which were observed in HE-stained
      sections and positive/negative for GGT was 6.17 and 8.17, respectively. In
      Experiment II, the total multiplicity of hepatocellular foci in paraffin-embedded
      sections which were observed in HE-stained sections and positive/negative for
      CK8/18 was 4.47 and 23.17, respectively, while that of hepatocellular foci in
      frozen sections which were observed in HE-stained sections and positive/negative
      for GGT was 2.50 and 3.50, respectively. Most of the hepatocellular adenomas and
      carcinomas observed in HE-stained sections were positive for CK8/18, but some of
      the adenomas were negative for CK8/18. These findings indicate that more
      hepatocellular proliferative lesions can be detected in CK8/18
      immunohistochemistry in addition to those observed in HE-stained sections, and
      suggest that CK8/18 may become a useful immunohistochemical marker for detecting
      hepatocellular proliferative lesions in mice.

PMID- 20035117
TI  - Induction of immune suppression in the chick by an optimal dose of an immunizing
      antigen in the presence of its specific maternal antibody.
AB  - Prolonged interference or suppression of maternal antibodies of the humoral
      immune response of newly hatched chicks to active immunization has been
      documented; however, the immunological mechanisms responsible for such
      suppression are still unclear. Laying hens were immunized with dinitrophenyl
      keyhole limpet hemocyanin (DNP-KLH). Purified maternal anti-DNP or non-specific
      IgY antibodies were transferred by yolk sac inoculation to newly hatched chicks,
      and they were immunized with DNP-KLH or rabbit serum albumen (RSA) at 1 and 4
      weeks of age. The concentrations of anti-DNP and anti-RSA antibodies in serum
      samples of these chicks were measured using an enzyme-linked immunosorbent assay
      (ELISA). The immune responses of the chicks that received a high dose of maternal
      anti-DNP antibodies and were immunized with an appropriate dose of DNP-KLH were
      suppressed. However, those of the chicks that received the same high dose of
      maternal non-specific IgY antibodies and were immunized with an appropriate dose
      of DNP-KLH and those of the chicks that received a high dose of maternal anti-DNP
      antibodies and were immunized with RSA were not suppressed. On the other hand,
      suppression of anti-DNP antibody production would not be induced if the chicks
      received a high dose of antigen specific maternal antibodies and were immunized
      with a high dose of the same antigen. These results revealed that the immune
      suppressive effect of maternal antibodies on the immune response of the newly
      hatched chicks was antigen specific and depended mainly on the ratio of
      antigen/maternal antibody at the time of immunization.

PMID- 20035118
TI  - Alpha-linked galactooligosaccharide suppresses small intestinal eosinophil
      infiltration and improves growth performance in weaning pigs.
AB  - A healthy pig shows significant eosinophil infiltration in the lamina propria of
      the small intestine. Although the exact role of these infiltrated eosinophils in
      healthy pigs is unclear, eosinophil infiltration is a well-known phenomenon that
      is frequently observed during an allergic status. Alpha-linked
      galactooligosaccharide (GOS) reduces eosinophil infiltration into broncho
      alveolar lavage fluid of an allergic airway eosinophilia model. We evaluated the
      effect of GOS oral administration on the suppression of eosinophil infiltration
      in the small intestine of healthy weaned pigs. Nine 21-day-old pigs were
      purchased and divided into three groups. One group was fed the basal diet
      supplemented with sucrose at 0.11% (C), one group was fed the basal diet
      supplemented with GOS at 1.17% (GOS A) and one group was fed the basal diet
      supplemented with GOS at 0.03% (GOS B). Each group was fed its respective diet
      throughout this study (10 days). The daily body weight gain from d3 to d10 was
      significantly bigger in the GOS B group than in the other groups. The feed
      conversion ratios from d0 to d10 were two times lower in the GOS B group than in
      the C group. Dietary GOS suppressed eosinophil infiltration in the small
      intestine. However, GOS administration had no effect on the organic acid level or
      microbial composition in the small and large intestinal digesta.

PMID- 20035119
TI  - Genetic analysis of beak and feather disease virus derived from a cockatiel
      (Nymphicus hollandicus) in Japan.
AB  - Psittacine beak and feather disease (PBFD), which is caused by beak and feather
      disease virus (BFDV), has been reported in a wide range of psittacine species,
      except the cockatiel (Nymphicus hollandicus), in which PBFD has rarely been
      reported. We detected BFDV from a case of PBFD in a cockatiel in the present
      study. The virus was designated CO-JA. The whole genome sequence of CO-JA had
      from 86 to 98% homology with BFDVs in psittacine species. CO-JA clustered with
      isolates derived from other cockatoos in phylogenetic analyses based on two major
      virus proteins. We concluded that genetic data cannot explain the reason why PBFD
      is rarely found in the cockatiel.

PMID- 20035120
TI  - Radiographic measurement of cardiac size in 27 rabbits.
AB  - Right lateral position (RL) chest radiograms were obtained from 27 heart disease
      free rabbits, and cardiac sizes were compared according to body weight (<1.6 vs.
      > or =1.6 kg) and gender (female vs. male). Significant differences (P<0.05) were
      observed in RL-long axis (RL-LA) and RL-vertebral heart size (RL-VHS). RL-LA was
      4.22 +/- 0.25 and 4.48 +/- 0.3, and RL-VHS was 7.55 +/- 0.38 and 7.99 +/- 0.58,
      in the <1.6 kg (n=12) and > or =1.6 kg (n=15) groups, respectively. These values
      should prove useful as new diagnostic indices for cardiac disease in rabbits.

PMID- 20035121
TI  - Occurrence of a pig respiratory disease associated with swine influenza A (H1N2)
      virus in Tochigi Prefecture, Japan.
AB  - In February 2008, a feeder pig herd of the affected farm in Tochigi Prefecture,
      Japan, showed increasing respiratory symptoms; by April, the situation worsened
      with 12-16 pigs dying daily. Diagnostic tests revealed the presence of H1N2
      subtype of swine influenza virus (SIV) and Pasteurella multocida from nasal swab
      and lung emulsion. Serological tests by hemagglutination inhibition method and
      enzyme-linked immunosorbent assay method (ELISA; imported from U.S.A.) indicated
      the spread of SIV into the pig herds of the affected farm around April 2008. The
      severe infection and subsequent damage were considered as a result of the
      combined infection of SIV (H1N2) and bacteria that may have been prevalent in the
      pig farm. Genetic homology search of sequences for the hemagglutinin (HA) and
      neuraminidase (NA) genes of A/swine/Tochigi/1/08 showed high homology to Japanese
      SIVs (H1N2) isolated in the 2000s. Therefore, we considered that Japanese SIV
      (H1N2) has established an independent stable lineage and participated in
      infecting pig populations as one of the factors of the pig respiratory disease
      complex. Consistent surveillance would contribute to clarifying the prevalence of
      dominant SIVs.

PMID- 20035122
TI  - Effects of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid on T2
      weighted MRCP.
AB  - PURPOSE: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB
      DTPA) is a recently developed liver-specific contrast agent for magnetic
      resonance (MR) imaging that is excreted equally via the kidneys and the biliary
      system. To our knowledge, its effects on T(2)-weighted MR
      cholangiopancreatography (MRCP) images have not been explored. Acquisition of the
      hepatobiliary phase is recommended 20 min after administration of Gd-EOB-DTPA.
      Examination time cannot be extended if the contrast does not take effect on T(2)
      weighted MRCP within 20 min after administration. We attempted to assess the
      change in signal of T(2)-weighted MRCP by excretion of Gd-EOB-DTPA. METHODS:
      Between March and July 2008, 40 patients (15 women, 25 men; mean age 70.8 years)
      were examined with abdominal MR imaging. T(2)-weighted MRCP was performed before
      and 10 and 20 min after administration of Gd-EOB-DTPA. We analyzed signal
      intensity of the bile duct, gallbladder, cystic duct, and pancreatic duct on MRCP
      for changes in intensity. RESULTS: T(2)-weighted MRCP 20 min after contrast
      administration showed loss of signal of the bile duct (intrahepatic bile duct in
      all cases, upper extrahepatic duct in 36 [90%], middle extrahepatic duct in 33
      [85%], and lower extrahepatic duct in 26 [67%]), the gallbladder in 23 cases
      (72%), and the cystic duct in 25 (64%). This signal change increased with time.
      We observed no change in signal of the pancreatic duct. CONCLUSION: T(2)-weighted
      MRCP sequences should not be obtained after administration of Gd-EOB-DTPA because
      this contrast agent decreases signal intensity of the biliary structure on these
      images.

PMID- 20035123
TI  - Modified echo peak correction for radial acquisition regime (RADAR).
AB  - PURPOSE: Because radial sampling imposes many limitations on magnetic resonance
      (MR) imaging hardware, such as on the accuracy of the gradient magnetic field or
      the homogeneity of B(0), some correction of the echo signal is usually needed
      before image reconstruction. In our previous study, we developed an echo-peak
      shift correction (EPSC) algorithm not easily affected by hardware performance.
      However, some artifacts remained in lung imaging, where tissue is almost absent,
      or in cardiac imaging, which is affected by blood flow. In this study, we
      modified the EPSC algorithm to improve the image quality of the radial aquisition
      regime (RADAR) and expand its application sequences. METHODS: We assumed the
      artifacts were mainly caused by errors in the phase map for EPSC and used a
      phantom on a 1.5-tesla (T) MR scanner to investigate whether to modify the EPSC
      algorithm. To evaluate the effectiveness of EPSC, we compared results from T(1)-
      and T(2)-weighted images of a volunteer's lung region using the current and
      modified EPSC. We then applied the modified EPSC to RADAR spin echo (SE) and
      RADAR balanced steady-state acquisition with rewound gradient echo (BASG)
      sequence. RESULTS: The modified EPSC reduced phase discontinuity in the reference
      data used for EPSC and improved visualization of blood vessels in the lungs.
      Motion and blood flow caused no visible artifacts in the resulting images in
      either RADAR SE or RADAR BASG sequence. CONCLUSION: Use of the modified EPSC
      eliminated artifacts caused by signal loss in the reference data for EPSC. In
      addition, the modified EPSC was applied to RADAR SE and RADAR BASG sequences.

PMID- 20035124
TI  - MR angiography for detecting the artery of Adamkiewicz and its branching level
      from the aorta.
AB  - PURPOSE: We evaluated the efficacy of magnetic resonance angiography (MRA) for
      detecting the artery of Adamkiewicz (AKA) and the vertebral level of its feeding
      arteries branching from the aorta. MATERIALS AND METHODS: Eighty-two patients (67
      men, 15 women; aged 34 to 86 years, mean age 68.6 years) with thoracic descending
      and thoracoabdominal aortic lesions (aneurysm in 55, dissection in 25,
      coarctation in 2) underwent MRA to detect AKA. MRA was performed using 6-phase,
      dynamic-enhanced, 3-dimensional, fast spoiled gradient recalled acquisition in
      steady state (GRASS) on a 1.5-tesla (T) system, with double-dose bolus contrast
      injection. The vertebral levels of AKA branching and the AKA feeder artery
      branching from the aorta were determined. RESULTS: The AKA was detected in 67
      patients (81.7%). Branching of AKA occurred at levels T7 to T12 on the left side
      (n=52) and on the right (n=15). Vascular continuity from the aorta to the
      anterior spinal artery was demonstrated in 55 patients (67.1%). Comparing the
      vertebral level of arterial branching from the aorta to that of the AKA at the
      intervertebral foramen, the AKA branched at the same vertebral level in 44
      patients (80.0%), one vertebral level above/below in 10 (18.2%), and 2 vertebral
      levels above in one (1.8%). CONCLUSION: MRA can be useful in the preoperative
      work-up of patients with thoracoabdominal aortic lesions to localize AKA and the
      segmental trajectories of vessels supplying blood to the AKA.

PMID- 20035125
TI  - MR tractography: a review of its clinical applications.
AB  - Magnetic resonance tractography based on diffusion-tensor imaging was first
      introduced to the medical imaging community a decade ago. It has been
      successfully applied to a number of neurological conditions and most commonly
      used for preoperative planning for brain tumors and vascular malformations. Areas
      of active research include stroke, and dementia, where it provides valuable
      information not available through other imaging techniques. This technique was
      first introduced using the deterministic streamline algorithm and has evolved to
      use more sophisticated probabilistic approaches. We will review the past,
      present, and future of tractography, focusing primarily on its clinical
      applications.

PMID- 20035126
TI  - T1-weighted MR imaging of the female pelvis using RADAR-FSE sequence.
AB  - Radial scanning is attracting increasing attention as a method of suppressing
      motion artifacts in magnetic resonance imaging. We compared the effectiveness of
      radial acquisition regime-fast spin echo (RADAR-FSE), a method of radial
      scanning, with conventional FSE in the T(1)-weighted imaging setting by scanning
      Gd-DTPA phantoms and 9 female patients (pelvic imaging). RADAR-FSE suppressed
      motion artifacts better than FSE but caused streak artifacts and diminished
      sharpness. Clinicians should be aware of these limitations.

PMID- 20035127
TI  - Introducer needles of peripheral intravenous catheters: assessment of magnetic
      field interactions with 1.5T and 3T MR systems.
AB  - We developed a peripheral intravenous catheter introducer that can be used safely
      in the magnetic resonance (MR) environment, including that at 3.0-tesla. We
      evaluated introducers with stainless steel (SUS 316L) and nickel-chromium-based
      (inconel 600) needles as well as a 20-gauge peripheral intravenous catheter
      introducer with SUS 304 needle for MR safety. From an MR safety standpoint, the
      SUS 304 should not be selected, and though inconel 600 is the preferred material,
      the SUS 316L introducer may be more practical with some modifications.

PMID- 20035128
TI  - Detection of presumed hemorrhage in the ampullar endolymph of the semicircular
      canal: a case report.
AB  - We examined a 61-year-old woman with sudden left-side hearing loss accompanied by
      severe vertigo. High signal in the ampullar endolymph of the left semicircular
      canal on magnetic resonance (MR) fluid attenuated inversion recovery (3D-FLAIR)
      images suggested labyrinthine hemorrhage. The patient had been treated for
      chronic heart failure and prescribed 100 mg/day of acetylsalicylic acid (aspirin)
      for its antiplatelet effect. The 3D-FLAIR images demonstrated a small amount of
      focal hemorrhage in the labyrinthine fluid that may have been overlooked on T(1)
      weighted images.

PMID- 20035129
TI  - MR diagnosis of steroid cell tumor of the ovary: value of chemical shift imaging.
AB  - A 53-year-old asymptomatic woman was found to have a pelvic mass at medical
      examination. Magnetic resonance (MR) imaging revealed a 4-cm solid mass at the
      right adnexal region, which showed marked hyperintensity on T(2)-weighted imaging
      and marked enhancement on post-contrast T(1)-weighted imaging. Chemical-shift
      imaging showed slight but significant signal loss on out-of-phase images, which
      suggested the presence of intratumoral lipid. The resected specimen exhibited
      typical features of steroid cell tumor, and Oil Red O stain was positive for
      cytoplasmic lipid.

PMID- 20035130
TI  - Endorsement of the FOUR score for consciousness assessment in neurosurgical
      patients.
AB  - The Full Outline of UnResponsiveness (FOUR) score was previously developed for
      neurological assessment, but has not been validated in neurosurgical patients, so
      was compared to the Glasgow Coma Scale (GCS) in practice. Four groups of raters,
      expert clinicians, novice clinicians, experienced nurses, and inexperienced
      nurses, assessed 64 patients in awake, drowsy, stuporous, and comatose conditions
      to investigate rater reliability. Then, 36 patients were evaluated by 1 expert
      clinician and 1 from the other groups randomly to test the difference. Spearman's
      correlation was used to find the correlation between both scores from 68
      patients. The estimation of FOUR score cut points was validated by weighted kappa
      compared with the GCS to establish the risk prognosis. Score feasibility was
      analyzed by nonparametric test. Intraclass correlation in each group was over
      0.9, with no difference between expert and inexperienced raters (p > 0.05). The
      correlation was 0.78. Low, intermediate, and high risk prognosis were associated
      with 0-7, 8-14, and 15-16 FOUR scores with kappa of 0.92. The feasibility of the
      FOUR score was lower than that of the GCS (p < 0.01). The FOUR score is reliable
      and valid for consciousness evaluation with some consequences for practicability.
      Extensive implementation would increase familiarity.

PMID- 20035131
TI  - Novel antitumor effect of carboplatin delivered by intracerebral microinfusion in
      a rat malignant glioma model.
AB  - Carboplatin loaded osmotic mini-pumps were implanted in 24 9L malignant glioma
      bearing rats to investigate the implications of direct intracerebral
      microinfusion. Carboplatin using 0.1 mg/ml (low dose group) or 1.0 mg/ml (high
      dose group) with eight rats in each group, or 5% D-glucose (control group) in
      eight rats were infused at 1 microl/hr for 7 days. The tumor volume was serially
      measured by magnetic resonance (MR) imaging with gadolinium as the enhanced area,
      and the survival periods and histological findings were also examined.
      Separately, to examine the effects of intracerebral carboplatin infusion on
      vascular permeability, tumor-bearing rats received intravenous administration of
      2% Evans blue at 21 days after infusion. The high dose group showed transient
      increase of enhanced volume at 21 days associated with mass effect, and
      significantly decreased tumor volume at 28 and 35 days compared with the control
      and low dose groups. The high dose group showed significant longer survival time
      than the control and low dose groups. Histological examination of the high dose
      group at 21 days showed the central tumor necrotic area around the infusion site
      and Evans blue leakage into the surrounding enhanced rim and the necrotic core.
      Therefore, leakage of plasma fluid into the necrotic area was considered to be
      the cause of apparent transient swelling. The present study demonstrated
      quantitatively using MR imaging that intracerebral carboplatin microinfusion
      significantly inhibited the rapid growth of experimental rat glioma but that the
      high dose required carries the risk of transient swelling of the target tumor.

PMID- 20035132
TI  - Surgical strategy for tumors located in or extending from the intracranial space
      to the infratemporal fossa-Advantages of the transcranial approach (zygomatic
      infratemporal fossa approach) and the indications for a combined transcranial and
      transcervical approach-.
AB  - The surgical strategy for tumors located in or extending from the intracranial
      space to the infratemporal fossa was analyzed in 12 cases with various
      pathologies. A case of mandibular nerve schwannoma, which extended 1 cm below the
      external orifice of the foramen ovale, was completely removed via the epidural
      subtemporal approach without zygomatic osteotomy with partial removal of the
      middle cranial base. The inferior margin of infratemporal tumor could be accessed
      via the transcranial route with zygomatic or orbitozygomatic osteotomy without
      complications including facial nerve injury in nine cases, and the lowest level
      of the infratemporal tumors was approximately 4.5 cm below the outer surface of
      the middle cranial base. In five of these 9 cases (2 schwannomas, 1 myxoma, 1
      chondrosarcoma, and 1 malignant peripheral nerve sheath tumor), the tumors were
      localized in the infratemporal fossa, and in the other 4 cases (2 meningiomas, 1
      glioblastoma, and 1 ameloblastoma), the tumors extended to both the intracranial
      space and the infratemporal fossa. In two cases (recurrent jugular schwannoma and
      mandibular osteosarcoma), a combined transcranial and transcervical approach
      (mandibular swing approach) was essential, because the resection line of the
      lower margin was too far from the middle cranial base. These results indicate
      that the transcranial approach, with or without zygomatic or orbitozygomatic
      osteotomy (zygomatic infratemporal fossa approach), is safe and effective for
      removal of some infratemporal tumors, and that a combined transcranial and
      transcervical approach is useful for removing infratemporal tumors with extensive
      downward extension.

PMID- 20035133
TI  - Traumatic aneurysm of the supraclinoid internal carotid artery-case report-.
AB  - A 23-year-old male was admitted after a motor vehicle accident with acute
      epidural hematoma, diffuse subarachnoid hemorrhage (SAH) in the basal cistern,
      and fractures at the anterior cranial base. Angiography revealed an aneurysm of
      the right supraclinoid internal carotid artery (ICA). His consciousness suddenly
      worsened on the 23rd day. Expansion of the SAH in the basal cistern and two hump
      aneurysms were detected. He underwent endovascular embolization of these
      aneurysms and the right ICA with Guglielmi detachable coil. Traumatic aneurysms
      are difficult to diagnose in the early period after injury and are associated
      with a high mortality. Endovascular treatments for traumatic aneurysms have lower
      mortality rate, and can be performed under local anesthesia.

PMID- 20035134
TI  - Unstable stenosis of the internal carotid artery caused by a craniofacial nail
      gun injury-case report-.
AB  - A 30-year-old carpenter suffered accidental piercing of his jaw by a 3-inch nail
      from a nail gun. No neurological deficits were found on admission. Computed
      tomography showed that the tip of the nail had reached the foramen lacerum.
      Cerebral angiography revealed severe stenosis at the C(4) portion of the left
      internal carotid artery (ICA) and marked decrease in the flow of the distal ICA.
      He had developed right hemiparesis and sensory aphasia by the following morning.
      T(2)-weighted and fluid-attenuated inversion recovery magnetic resonance imaging
      showed a focal hyperintense signal in the left central region indicating cerebral
      infarction. Repeat angiography demonstrated that the antegrade blood flow from
      the occluded point on the admission day had partially resumed, and endovascular
      trapping of the ICA was successfully carried out. The nail was then removed
      safely without problematic bleeding. The patient suffered no additional deficit,
      and his sensory aphasia and right hemiparesis gradually improved. The fluctuating
      blood flow through the unstable stenosis of the ICA related to nail movement
      possibly caused the delayed cerebral infarction. To avoid the occurrence of such
      events, rapid treatment after necessary investigations is recommended in patients
      with craniofacial penetrating injuries that affect the ICA.

PMID- 20035135
TI  - Brain stem hemorrhage following burr hole drainage for chronic subdural hematoma
      case report-.
AB  - A 76-year-old man presented with brain stem hemorrhage after burr-hole drainage
      for bilateral chronic subdural hematomas. Neuroimaging demonstrated resolution of
      the transtentorial herniation but also detected new brain stem hemorrhage,
      manifesting as gait disturbance. He recovered after conservative treatment.
      Asymmetrical and rapid decompression, which leads to vascular disruption and/or
      sudden increase in cerebral blood flow, was probably responsible for the
      secondary brain stem hemorrhage. Therefore, simultaneous and bilateral
      decompression with a slow rate of evacuation of massive bilateral chronic
      subdural hematomas is recommended to prevent serious complications such as
      secondary intracranial hematoma.

PMID- 20035136
TI  - Rebleeding from a vertebral artery dissecting aneurysm after endovascular
      internal trapping: adverse effect of intrathecal urokinase injection or
      incomplete occlusion?-case report-.
AB  - A 67-year-old woman suffered rebleeding from a ruptured vertebral artery
      dissecting aneurysm after endovascular internal trapping. The dissecting aneurysm
      was initially successfully occluded with the affected vertebral artery using
      detachable coils. However, rebleeding from the aneurysm occurred on the next day.
      The rebleeding may have resulted from the thrombolytic effect of urokinase, which
      was injected intrathecally 3 hours before rebleeding occurred, or the relatively
      loose coil packing of the aneurysm. This case indicates the potential risk of
      intrathecal use of thrombolytic agents and the importance of complete tight coil
      packing of the whole dissected site in the treatment of ruptured vertebral artery
      dissecting aneurysms.

PMID- 20035137
TI  - Direct clipping of a thrombosed giant cerebral aneurysm after thrombectomy
      without bleeding to minimize the temporary occlusion time-technical case report-.
AB  - A 75-year-old man was referred to our hospital with a thrombosed giant middle
      cerebral artery aneurysm manifesting as progressive memory disturbance and
      disorientation. Magnetic resonance imaging and conventional angiography revealed
      a partially thrombosed giant aneurysm of the left middle cerebral artery
      bifurcation and edema of the adjacent brain which had enlarged compared to 3
      months before. Surgery was performed through a left frontotemporal craniotomy.
      After exposure of the aneurysm neck, we tried to apply a clip, which slipped due
      to the intraaneurysmal thrombus. Intraoperative motor evoked potential monitoring
      showed decreased amplitude. Therefore, the aneurysm dome was incised and the
      intraaneurysmal thrombus near the neck was shaved with the ultrasonic aspirator,
      followed by neck clipping of the aneurysm. The residual thrombus was safely
      removed. Transient right hemiparesis was observed after surgery, but his memory
      disturbance gradually improved. Giant thrombosed aneurysm can be treated by
      reduction of the thrombus from the far side to the lumen to reduce the duration
      of parent artery occlusion required for clipping.

PMID- 20035138
TI  - Usefulness of intravascular ultrasonography monitoring of coil embolization for
      traumatic direct carotid-cavernous fistula-case report-.
AB  - A 61-year-old woman was admitted for head injury after a traffic accident. Two
      months later, she developed abducens nerve palsy, chemosis, and pulsatile
      tinnitus. Right internal carotid angiography demonstrated a high flow direct
      carotid-cavernous fistula (CCF) at the C(5) portion with reflux into the
      superficial and deep sylvian veins, superior ophthalmic vein, superior petrosal
      sinus, and inferior petrosal sinus. Intravascular ultrasonography (IVUS) revealed
      a large fistula at the C(5) portion of the internal carotid artery (ICA). Coil
      embolization via transarterial and transvenous approaches under IVUS monitoring
      was performed. During the procedure, IVUS accurately detected protrusion of a
      coil into the parent ICA, and the parent artery could be preserved. IVUS
      monitoring is useful for embolization of direct CCF with coils.

PMID- 20035139
TI  - Differentiation of clear cell ependymoma of the cerebellum from hemangioblastoma
      by thallium-201 single photon emission computed tomography-case report-.
AB  - A 57-year-old man suffered from dizziness for about one year and truncal ataxia
      for about one month. Magnetic resonance imaging demonstrated a cystic tumor with
      a homogeneously enhanced mural nodule located in the cerebellar vermis. Computed
      tomography angiography revealed a hypervascular nodule. These findings were
      compatible with hemangioblastoma. Thallium-201 single photon emission computed
      tomography ((201)Tl-SPECT) showed moderately high uptake in the early phase and
      moderately high retention in the delayed phase, whereas hemangioblastoma shows
      almost no retention in the delayed phase. The patient underwent total removal of
      the tumor. The histological diagnosis was clear cell ependymoma (CCE). CCE is a
      rare subtype of ependymoma, which resembles hemangioblastoma in histological and
      neuroimaging findings, but is considerably more aggressive. (201)Tl-SPECT can
      provide useful information for the preoperative differential diagnosis of
      infratentorial CCE and hemangioblastoma.

PMID- 20035140
TI  - Isolated recurrence of granulocytic sarcoma-two case reports-.
AB  - Two patients presented with rare isolated recurrence of granulocytic sarcoma. A
      29-year-old male presented with an extra- and intracranial mass 10 years after
      bone marrow transplantation for chronic myeloid leukemia. A 34-year-old female
      presented with an intracranial mass 3 years after complete remission of acute
      myeloid leukemia-M2a. Both patients underwent surgical resection. The first
      patient received adequate postoperative radiotherapy and chemotherapy, and
      achieved complete remission without evidence of diseases during the 6-month
      follow up. The second patient only received whole brain radiotherapy, failed to
      respond, and died of systemic leukemia later. These two cases demonstrate that
      neurosurgeons should pay attention to the occurrence of isolated recurrent
      granulocytic sarcoma, especially in patients with a history of hematologic
      neoplasm. Immediate pathological and cytogenetic diagnoses are essential.

PMID- 20035141
TI  - Surgical treatment of spinal lipoma without spina bifida at lumbar region-three
      case reports-.
AB  - Three men aged 40 to 60 years presented with rare lumbar spinal intradural
      lipomas without spina bifida manifesting as worsening numbness, pain of the lower
      extremities, and bladder dysfunction. All 3 patients underwent decompressive
      laminectomy. The lipoma and cauda equina nerves were dissected from the dura
      mater under the operating microscope, untethering the spinal cord and returning
      the cauda equina nerves to the original position. Duralplasty was performed using
      an expanded polytetrafluoroethylene sheet. Postoperatively, all patients
      experienced improvement of their neurological deficits. In the surgical treatment
      of spinal lipomas, the primary purpose is untethering and decompression, which
      can be achieved by untethering the spinal cord, returning the cauda equina nerves
      to the normal position, laminectomy, and duralplasty, without removal of the
      lipoma.

PMID- 20035142
TI  - Focal hand dystonia cured by removal of clinoid meningioma-case report-.
AB  - A 40-year-old Asian female presented with an unusual case of focal hand dystonia
      caused by contralateral clinoid meningioma. Magnetic resonance imaging showed
      that the tumor compressed the caudate nucleus, lentiform nucleus, cerebral
      peduncle, internal capsule, and a large portion of the white matter surrounding
      the basal ganglia. The tumor was gross totally removed via a frontotemporal
      approach with zygomatic osteotomy, resulting in cure of the focal hand dystonia.
      Magnetic resonance imaging after surgery showed that the compression of the
      surrounding brain was released. This case shows that secondary focal hand
      dystonia caused by extra-axial brain tumor can be cured by surgical removal.

PMID- 20035143
TI  - Hypophysitis presenting with atypical rapid deterioration: with special reference
      to immunoglobulin G4-related disease-case report-.
AB  - Primary hypophysitis is believed to be a chronic inflammation of the pituitary
      tissue caused by the autoimmune mechanism. The disease can be classified based on
      morphology and histology simultaneously, but the relationships between these
      subtypes remain unclarified. Moreover, hypophysitis may occur as a part of
      systemic immunoglobulin G4 (IgG4)-related plasmacytic disease. A 74-year-old
      woman was initially diagnosed with infundibulo-hypophysitis. After a long period
      of stability, she suffered rapid deterioration with evolving endocrinopathies and
      visual symptoms. Biopsy specimen established the diagnosis as granulomatous
      hypophysitis with positive reaction for IgG4 in infiltrating plasma cells.
      Postoperative glucocorticoid administration improved her condition dramatically.
      This case illustrates two interesting points: The rapid deterioration after a
      long stable clinical course, and the presence of IgG4-positive tissue in the
      pituitary gland, which can be considered as "primary" hypophysitis with no
      systemic IgG4-related disease in other organs.

PMID- 20035144
TI  - Blurred vision with acute hypertension indicating hypertensive brainstem
      encephalopathy-case report-.
AB  - A 49-year-old woman presented with hypertensive brainstem encephalopathy (HBE)
      manifesting as visual disturbance and papilledema but no other neurological
      abnormal findings. Magnetic resonance (MR) imaging showed extensive lesions in
      the brainstem and bilateral thalami but not in the occipital lobes. The patient
      also had renal failure and underwent hemodialysis. Her visual disturbance and MR
      lesions resolved rapidly after antihypertensive treatment. This case of HBE only
      caused visual disturbance despite the presence of massive brainstem edema. The
      presence of fetal-type posterior cerebral artery may have spared the occipital
      lobe. Clinicians should consider HBE in hypertensive patients with blurred
      vision. HBE is reversible if immediate antihypertensive treatment is initiated,
      but neurological sequelae may develop if treatment is delayed.

PMID- 20035145
TI  - Correlation between peripheral blood T-cell profiles and clinical and
      inflammatory parameters in stable COPD.
AB  - BACKGROUND: Recent studies suggest that Tc1/Tc2 imbalances are implicated in the
      pathogenesis of chronic obstructive pulmonary disease (COPD). The purpose of this
      study was to clarify the relationship between peripheral blood T-cell profiles
      and pulmonary function or inflammatory parameters. METHODS: Thirty-one patients
      with stable COPD (median age 70 years, 30 males, 15 current smokers and 16 ex
      smokers) and 30 healthy control subjects were enrolled in this study. The
      subjects underwent blood tests, exhaled nitric oxide (eNO) measurement, pulmonary
      function tests, and sputum induction. Tc1/Tc2 and Th1/Th2 were determined by
      analyzing intracellular cytokine staining for IFN-gamma and IL-4 in peripheral
      blood CD8+ and CD4+ T cells using flow cytometry after stimulation with phorbol
      12-myristate 13-acetate and ionomycin. RESULTS: There was a significantly
      increased proportion of IFN-gamma-producing and IL-4-producing CD8+ T cells in
      patients with COPD compared with control subjects (median [IQR] 73.6% [63.9%
      80.7%] vs 62.0% [45.6%-73.8%], p=0.004; and 2.6% [1.1%-6.9%] vs 1.1% [0.6%-2.2%],
      p=0.002, respectively). In addition, the proportion of IFN-gamma-producing CD4+ T
      cells was significantly higher in patients with COPD compared with control
      subjects (25.7% [21.2%-38.0%] vs 22.8% [15.6%-29.2%], p=0.027). The proportion of
      IFN-gamma-producing CD8+ T cells was correlated negatively with single-breath
      carbon monoxide transfer coefficient (Kco)(rho=-0.45, p=0.033) and positively
      with eNO (rho=0.50, p=0.012). The proportion of IL-4-producing CD8+ T cells was
      positively correlated with body mass index (rho=0.42, p=0.023) and Kco (rho=0.47,
      p=0.026). CONCLUSIONS: It is suggested that Tc1 cells have a detrimental role and
      that Tc2 cells have a protective role in disease progression.

PMID- 20035146
TI  - Comparison of effectiveness in ciclesonide and fluticasone propionate on small
      airway function in mild asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICS) are the mainstay of asthma treatment,
      but conventional ICS may have limited effectiveness in inflammation and patency
      of small airways. Ciclesonide is delivered and deposited in the peripheral region
      of the lung as a small particle corticosteroid. The aim of the study is to
      compare the effects of ciclesonide with fluticasone propionate on small airway
      function in asthma. METHODS: Thirty mild persistent asthma patients treated with
      200 microg of fluticasone propionate were randomized to receive either
      ciclesonide 200 microg once daily or fluticasone propionate 100 microg twice
      daily for 8 weeks. Small airway function was assessed by impulse oscillometry
      (IOS) and percentage of eosinophil induced sputum. RESULTS: We observed that
      ciclesonide significantly improved IOS measured resistance of small airways (R5
      R20; p<0.05), distal reactance (X5; p<0.01), reactance area (AX; p<0.01), and
      decreased late-phase sputum eosinophil level (p<0.01) compared with fluticasone
      propionate. There were no significant changes in spirometry indices in either
      group during the study. CONCLUSIONS: These findings suggest that ciclesonide
      improves small airway function and inflammation compared with fluticasone
      propionate in mild asthma. This study provides evidence that IOS and late-phase
      induced sputum allows detection of changes in the small airways that can not be
      detected by spirometry.

PMID- 20035147
TI  - Naringenin chalcone suppresses allergic asthma by inhibiting the type-2 function
      of CD4 T cells.
AB  - BACKGROUND: Some polyphenols possess anti-allergic activities. Naringenin
      chalcone is one of the polyphenols that is present in the skin of red tomatoes.
      In this study, we investigated the effect of naringenin chalcone in allergic
      responses in vivo using an experimental mouse model system of allergic asthma.
      METHODS: Allergic airway inflammation was induced in mice by sensitization and
      challenge with ovalbumin. Naringenin chalcone was orally administrated every day
      during the course of the experiment. Airway hyperreactivity, the eosinophilic
      infiltration in the bronchioalveolar lavage fluid and Th2 cytokine production
      from splenic CD4 T cells were assessed. RESULTS: Eosinophilic airway
      inflammation, airway hyperreactivity and Th2 cytokine production from CD4 T cells
      were significantly suppressed in mice that were treated with naringenin chalcone.
      Hyperproduction of mucus was slightly reduced. CONCLUSIONS: The results of this
      study suggest that naringenin chalcone suppresses asthmatic symptoms by
      inhibiting Th2 cytokine production from CD4 T cells. Thus, naringenin chalcone
      may be a useful supplement for the suppression of allergic symptoms in humans.

PMID- 20035148
TI  - IgG4+ plasma cell infiltrates in liver explants with primary sclerosing
      cholangitis.
AB  - Sclerosing cholangitis can be primary (PSC) or secondary. One unusual cause of
      secondary sclerosing cholangitis is the newly recognized entity of IgG4
      associated cholangitis. The prevalence and significance of IgG4 plasma cells in
      patients, who are clinically and radiologically classified as PSC, however, are
      unknown. Clinical information and histology of liver explants of 98 consecutive
      liver transplants performed for PSC were reviewed. IgG4 immunohistochemical stain
      was performed on sections from hilar areas that contained large bile ducts and
      corresponding cholecystectomy specimens (available in 74 cases). Serum IgG4
      levels were measured in stored serum from 81 cases. Tissue IgG4 positivity
      (>or=10 IgG4+ plasma cells/high power field) was correlated with clinical
      features (age, sex, presence of inflammatory bowel disease and
      cholangiocarcinoma, pancreatogram, PSC duration, PSC recurrence after transplant,
      and number of acute rejection episodes) and histologic findings (periductal
      lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis) in
      the liver explants. Twenty-three (23%) liver explants showed periductal
      infiltration with IgG4+ plasma cells. Eighteen cases (22%) had elevated serum
      IgG4 levels, including 8 without tissue IgG4 positivity. All cases showed dense
      periductal fibrosis; none had storiform fibrosis or obliterative phlebitis. IgG4
      positivity in the liver strongly correlated with moderate-to-marked periductal
      lymphoplasmacytic inflammation (P=0.002). Clinically, IgG4 positivity in tissue,
      but not in serum, was correlated with shorter PSC duration before transplant and
      higher risk of recurrence after transplant. Nearly one quarter of explanted
      livers that carry a clinical diagnosis of PSC contain increased IgG4+ periductal
      plasma cell infiltrates and positive serum IgG4 levels. However, none of the
      explants show histologic features diagnostic of IgG4-associated cholangitis. PSC
      with tissue IgG4 positivity has a more aggressive clinical course manifested by
      shorter time to transplant and a higher likelihood of recurrence than IgG4
      negative PSC.

PMID- 20035149
TI  - Fibroadenoma and phyllodes tumors of anogenital mammary-like glands: a series of
      13 neoplasms in 12 cases, including mammary-type juvenile fibroadenoma,
      fibroadenoma with lactation changes, and neurofibromatosis-associated
      pseudoangiomatous stromal hyperplasia with multinucleated giant cells.
AB  - The authors present a series of 13 fibroepithelial neoplasms involving anogenital
      mammary-like glands, all occurring in 12 female patients, whose age at diagnosis
      ranged from 30 to 51 years (mean, 38 y; median, 42 y). All women presented with a
      solitary asymptomatic nodule in the vulva (n=8), perineum (n=2), or near the anus
      (n=2) ranging in size from 1.5 to 4.5 cm. Microscopically, 8 lesions were
      classified as fibroadenoma, and 5, including 1 recurrent tumor, as phyllodes
      tumor, of which 1 was benign and 4 low-grade malignant. In addition to
      conventional findings, we describe several hitherto unreported features including
      juvenile fibroadenoma-like proliferation, fibroadenoma with lactation change, and
      pseudoangiomatous stromal hyperplasia with multinucleated stromal giant cells in
      a patient with neurofibromatosis, type 1 all constituting potential diagnostic
      pitfalls, which are best averted by using the same approach to diagnosis as for
      their analogous mammary counterparts.

PMID- 20035150
TI  - The basaloid cell is the best tissue marker for human papillomavirus in invasive
      penile squamous cell carcinoma: a study of 202 cases from Paraguay.
AB  - Human papillomavirus (HPV) has been reported in 12-82% of penile squamous cell
      carcinomas (SCC). There is an association of the virus with basaloid and warty
      carcinomas but the reported prevalence is variable. The causes of these
      variations are not clear. They may be owing to geographic differences, the use of
      different techniques to detect HPV, the status of the original paraffin blocks,
      or to variable criteria in tumor classification. The aims of the study were to
      determine the prevalence of HPV in penile SCC and subtypes using a sensitive
      technique, to investigate genotypes involved, and to search for other morphologic
      features associated with the virus from a series of cases from Paraguay. HPV
      detection was done by SPF-10 polymerase chain reaction followed by DNA enzyme
      immunoassay and genotyping by LIPA 25 (version 1). Samples were tested at Catalan
      Institute of Oncology, Barcelona, and cross testing was carried out at the Delft
      Diagnostic Laboratories in The Netherlands. HPV was detected in 64 of 202 cases
      (32%). Thirteen tumors had multiple HPV genotypes. Most prevalent genotypes were
      HPV-16 (46 cases), HPV-6 (6 cases), and HPV-18 (4 cases), either in single or in
      multiple infections. HPV was preferentially associated with warty-basaloid (82%),
      basaloid (76%), and warty (39%) carcinomas and not detected in verrucous, mixed
      verrucous-papillary, pseudohyperplastic, and pseudoglandular SCCs. There was a
      strong association between HPV and higher histologic grade. Basaloid cells were
      more frequently found in HPV positive tumors (72%) and this association was
      statistically significant in univariate and multivariate analyses. Cells with
      koilocytotic features and keratinizing squamous cells were also present but to a
      much lesser degree (47% and 19%, respectively). In summary, HPV was found in a
      third of the cases and the most common genotype was HPV-16. Low-risk genotypes
      were rarely found in single infections, representing 4 cases among all analyzed
      (2%). There was an association between HPV presence and higher histologic grade
      and with basaloid, warty-basaloid, and warty carcinomas. Our results also suggest
      that, in penile SCC, the basaloid cell is the best tissue marker for oncogenic
      HPV infection.

PMID- 20035151
TI  - What is a cystic nephroma?

PMID- 20035152
TI  - Location of melanoma metastases in sentinel lymph nodes: what are the
      implications for histologic processing of sentinel lymph nodes in routine
      practice?

PMID- 20035156
TI  - Current Opinion in Anaesthesiology. Current world literature.

PMID- 20035159
TI  - Current world literature.

PMID- 20035163
TI  - Mortality associated with discordant responses to antiretroviral therapy in
      resource-constrained settings.
AB  - OBJECTIVES: We assessed mortality associated with immunologic and virologic
      patterns of response at 6 months of highly active antiretroviral therapy (HAART)
      in HIV-infected individuals from resource-limited countries in Africa and South
      America. METHODS: Patients who initiated HAART between 1996 and 2007, aged 16
      years or older, and had at least 1 measurement (HIV-1 RNA plasma viral load or
      CD4 cell count) at 6 months of therapy (3-9 month window) were included. Therapy
      response was categorized as complete, discordant (virologic only or immunologic
      only), and absent. Associations between 6-month response to therapy and all-cause
      mortality were assessed by Cox proportional hazards regression. Robust standard
      errors were calculated to account for intrasite correlation. RESULTS: A total of
      7160 patients, corresponding to 15,107 person-years, were analyzed. In
      multivariable analysis adjusted for age at HAART initiation, baseline clinical
      stage and CD4 cell count, year of HAART initiation, clinic, occurrence of an AIDS
      defining condition within the first 6 months of treatment, and discordant and
      absent responses were associated with increased risk of death. CONCLUSIONS:
      Similar to reports from high-income countries, discordant immunologic and
      virologic responses were associated with intermediate risk of death compared with
      complete and no response in this large cohort of HIV-1 patients from resource
      limited countries. Our results support a recommendation for wider availability of
      plasma viral load testing to monitor antiretroviral therapy in these settings.

PMID- 20035165
TI  - Is there any potential for first-line etravirine use? Analysis from a large data
      set of antiretroviral therapy-naive HIV-infected patients undergoing resistance
      test.

PMID- 20035164
TI  - Declines in mortality rates and changes in causes of death in HIV-1-infected
      children during the HAART era.
AB  - CONTEXT: Introduction of highly active antiretroviral therapy has significantly
      decreased mortality in HIV-1-infected adults and children. Although an increase
      in non-HIV-related mortality has been noted in adults, data in children are
      limited. OBJECTIVES: To evaluate changes in causes and risk factors for death
      among HIV-1-infected children in Pediatric AIDS Clinical Trials Group 219/219C.
      DESIGN, SETTING, AND PARTICIPANTS: Multicenter, prospective cohort study designed
      to evaluate long-term outcomes in HIV-1-exposed and infected US children. There
      were 3553 HIV-1-infected children enrolled and followed up between April 1993 and
      December 2006, with primary cause of mortality identified in the 298 observed
      deaths. MAIN OUTCOME MEASURES: Mortality rates per 100 child-years overall and by
      demographic factors; survival estimates by birth cohort; and hazard ratios for
      mortality by various demographic, health, and antiretroviral treatment factors
      were determined. RESULTS: Among 3553 HIV-1-infected children followed up for a
      median of 5.3 years, 298 deaths occurred. Death rates significantly decreased
      between 1994 and 2000, from 7.2 to 0.8 per 100 person-years, and remained
      relatively stable through 2006. After adjustment for other covariates, increased
      risk of death was identified for those with low CD4 and AIDS-defining illness at
      entry. Decreased risks of mortality were identified for later birth cohorts, and
      for time-dependent initiation of highly active antiretroviral therapy (hazard
      ratio 0.54, P < 0.001). The most common causes of death were "End-stage AIDS" (N
      = 48, 16%) and pneumonia (N = 41, 14%). The proportion of deaths due to
      opportunistic infections (OIs) declined from 37% in 1994-1996 to 24% after 2000.
      All OI mortality declined during the study period. However, a greater decline was
      noted for deaths due to Mycobacterium avium complex and cryptosporidium. Deaths
      from "End-stage AIDS," sepsis and renal failure increased. CONCLUSIONS: Overall
      death rates declined from 1993 to 2000 but have since stabilized at rates about
      30 times higher than for the general US pediatric population. Deaths due to OIs
      have declined, but non-AIDS-defining infections and multiorgan failure remain
      major causes of mortality in HIV-1-infected children.

PMID- 20035166
TI  - Friedewald equation underestimates low-denisty lipoprotein elevations for
      patients with high triglyceride levels in the ARTEMIS and TITAN trials.

PMID- 20035167
TI  - Avoid a different standard of care when applying results of Development of
      Antiretroviral Therapy in Africa (DART) study.

PMID- 20035168
TI  - Potential confounding of the association between exposure to nucleoside analogues
      and mitochondrial dysfunction in HIV-uninfected and indeterminate infants.

PMID- 20035170
TI  - Functional and radiographic results of patients with syndesmotic screw fixation:
      implications for screw removal.
AB  - OBJECTIVE: Screw fixation of the injured syndesmosis restores stability but may
      reduce motion. The purpose of this study is to determine whether functional
      outcomes and radiographic results after ankle fracture are affected by the status
      of the syndesmosis screw. DESIGN: Retrospective review of a consecutive clinical
      series. SETTING: Level 1 academic trauma center. PATIENTS: One hundred six adults
      were reviewed radiographically; mean follow up was 15 months (range, 4-30
      months). Seventy-six of the 106 patients completed formal functional testing;
      mean follow up was 23 +/- 13 months (range, 12-32 months). INTERVENTION: Open
      reduction and internal fixation, including fixation of the tibiofibular
      syndesmosis. MAIN OUTCOME MEASUREMENTS: Patients with intact, broken or loose, or
      removed syndesmosis screws were compared. Functional outcomes were measured using
      the Lower Extremity Measure and the Olerud Molander ankle score. Radiologic
      review included tibiofibular clear space, tibiofibular overlap, and medial clear
      space. RESULTS: Functional outcomes were improved in patients with fractured,
      loosened, or removed screws compared with those with intact screws. The Lower
      Extremity Measure score for patients with intact screws was 70 +/- 6 compared
      with 85 +/- 3 for fractured, loosened, or removed screws (P = 0.01). The Olerud
      Molander ankle score for patients with intact screws was 47 +/- 8.0 compared with
      64 +/- 4 for fractured, loosened, or removed screws (P = 0.04). There was no
      difference in outcome comparing fractured, loosened, and removed screws. The
      tibiofibular clear space was narrowed in patients with intact screws compared
      with removed, fractured, or loose screws. The tibiofibular clear space for intact
      screws was 3.1 +/- 0.2 compared with 4.1 +/- 0.2 for removed, fractured, or
      loosened screws (P = 0.005). There was no difference in outcome comparing large
      and small fragment screws. CONCLUSIONS: An intact syndesmosis screw was
      associated with a worse functional outcome compared with loose, fractured, or
      removed screws. However, there were no differences in functional outcomes
      comparing loose or fractured screws with removed screws. Screw removal is
      unlikely to benefit patients with loose or fractured screws but may be indicated
      in patients with intact syndesmosis screws.

PMID- 20035171
TI  - Outcome after unstable ankle fracture: effect of syndesmotic stabilization.
AB  - OBJECTIVE: This study was performed to evaluate the results of operative
      treatment of ankle fractures in patients who required syndesmotic stabilization
      in addition to malleolar fracture fixation compared with patients who required
      malleolar fixation alone. DESIGN: The authors conducted a retrospective review of
      prospectively collected data. SETTING: Academic medical center. PATIENTS: Between
      October 2000 and November 2006, 347 patients who underwent surgical repair of an
      unstable ankle fracture were enrolled in a prospective database. INTERVENTION:
      Patients who had an associated syndesmotic disruption requiring surgical
      stabilization in association with either an ankle fracture or a fracture
      dislocation were identified and compared with a cohort treated during the same
      time period who had sustained an ankle fracture or fracture-dislocation without
      syndesmotic disruption. MAIN OUTCOME MEASUREMENTS: All patients were followed and
      evaluated at 3, 6, and 12 months with clinical and radiographic examination as
      well as functional status (Short Musculoskeletal Functional Assessment, American
      Orthopaedic Foot and Ankle Society). Patient-reported pain and postoperative
      complications were recorded as well. RESULTS: Three hundred forty-seven patients
      met the inclusion criteria and had 1-year minimum follow up. Seventy-nine
      patients (23%) who had syndesmotic stabilization were identified and compared
      with 268 patients (77%) who did not. No differences were found between the two
      groups with respect to age or American Society of Anesthesiologists status;
      however, there was a greater percentage of men in the syndesmotic injury group (P
      = 0.04). There was a greater percentage of Type C fractures requiring syndesmosis
      stabilization, whereas Type B fractures were less likely to require syndesmosis
      stabilization (P = 0.001) At 6- and 12-month follow up, there was a clear
      difference in outcome based on American Orthopaedic Foot and Ankle Society and
      Short Musculoskeletal Functional Assessment scores; patients who underwent
      syndesmotic stabilization had worse American Orthopaedic Foot and Ankle Society
      scores with lower function ratings (P = 0.04) and worse pain ratings (P = 0.02).
      Short Musculoskeletal Functional Assessment scores were also worse at 12 months
      in patients who had syndesmotic stabilization because the dysfunction index was
      higher in the syndesmotic injury group (P = 0.009). Radiographically, 18 of 144
      (13%) syndesmotic screws were noted to be broken on follow-up radiographs, eight
      of which were subsequently removed. There were no other differences in
      complication rates. CONCLUSION: Patients who required syndesmotic stabilization
      in addition to malleolar fracture fixation had poorer outcomes at 12 months
      compared with patients who required malleolar fracture fixation alone. This
      information is important for patient counseling to manage expectations regarding
      outcomes after injury.

PMID- 20035172
TI  - Functional outcomes after syndesmotic screw fixation and removal.
AB  - OBJECTIVES: Ankle fractures with a syndesmotic injury have historically been
      treated with syndesmotic screw fixation. We compared range of motion and
      functional outcomes' scores to assess patient benefit from syndesmotic screw and
      plate removal. DESIGN: Level IV--case series. SETTING: Level I--trauma center.
      PATIENTS/PARTICIPANTS: Twenty-five consecutive patients with unstable ankle
      fractures and syndesmotic injury confirmed on magnetic resonance imaging.
      INTERVENTION: Locked syndesmotic screws and plates were removed; functional
      outcomes and range of motion were measured before and after screw removal. MAIN
      OUTCOME MEASUREMENTS: Foot and Ankle Outcome Score, Olerud and Molander Ankle
      Score, and physical examination RESULTS: There was a significant improvement in
      range of motion, Foot and Ankle Outcome, and Olerud and Molander Ankle scores at
      the immediate postoperative visit. This was not significantly changed at longer
      follow-up. There were no adverse events or complications in these patients. No
      patient had radiographic loss of syndesmotic reduction after screw removal.
      CONCLUSIONS: Locked screw and plate removal improved function both subjectively
      and objectively. Transsyndesmotic implant removal seems to assist improvements in
      the speed of rehabilitation.

PMID- 20035173
TI  - No difference in functional and radiographic results 8.4 years after
      quadricortical compared with tricortical syndesmosis fixation in ankle fractures.
AB  - OBJECTIVE: To assess long-term functional and radiologic results after two types
      of syndesmosis fixation, comparing one quadricortical syndesmotic screw fixation
      with two tricortical screw fixation in ankle fractures. DESIGN: Follow up of a
      previously conducted prospective, randomized clinical study. SETTING: University
      clinic, Level I trauma center. PATIENTS: Forty-eight patients with closed ankle
      fractures and concomitant syndesmotic rupture were operated on with
      quadricortical (n = 23) or tricortical (n = 25) syndesmotic fixation. RESULTS:
      Follow-up time was 8.4 years (range, 7.7-8.9 years). There were no statistical
      differences in the two groups regarding Olerud-Molander Ankle score, Orthopaedic
      Trauma Association score, or degree of osteoarthritis. Patients with a difference
      in the syndesmotic width between the operated and the nonoperated ankle of 1.5 mm
      or more showed a tendency toward poorer functional results (P = 0.056). Twenty
      one patients showed synostosis on plain radiographs. Of these, only seven
      patients had synostosis verified on computed tomography, all of whom had
      significantly worse function. Patients with a posterior fracture fragment at time
      of operation had poorer Olerud-Molander Ankle score (73.1 versus 85, P = 0.05)
      and all had osteoarthritis as compared with 55% of those without a posterior
      fragment. Obese patients (body mass index greater than 30 kg/m2) also had poorer
      Orthopaedic Trauma Association score, but neither obesity nor being overweight
      predicted late arthritis. CONCLUSIONS: Follow up 8.4 years after surgery of ankle
      fractures with syndesmotic injury showed satisfactory functional results with
      only minor differences between the two groups of syndesmotic fixation. Obese
      patients had significantly poorer functional results. The presence of a posterior
      fracture fragment was an important negative prognostic factor regarding
      functional results. Plain radiographs overestimated tibiofibular synostosis.
      Synostosis on computed tomography, however, predicted impaired ankle function. A
      difference in syndesmotic width 1.5 mm or greater between the two ankles seemed
      to be associated with an inferior clinical result.

PMID- 20035174
TI  - Outcomes of minimally invasive plate osteosynthesis for metaphyseal distal tibia
      fractures.
AB  - OBJECTIVE: Evaluation of clinical results and outcomes of low metaphyseal distal
      tibia fractures with minimal or no intra-articular involvement. These were
      treated using the minimally invasive plate osteosynthesis concept with a 3.5-mm
      locked medial tibial plafond plate and hybrid (locking and nonlocking) screw
      construct. SETTING: Level II regional trauma center. DESIGN: Consecutive case
      series of clinical outcomes using limb-specific and whole-person measures.
      INTERVENTION: Minimally invasive medial plating using hybrid locking and
      nonlocking techniques. MAIN OUTCOME MEASUREMENT: The following were applied at a
      minimum of 2 years: limb assessment--Olerud and Molander's ankle rating scale and
      the American Orthopaedic Foot and Ankle Surgeon's (AOFAS) ankle-hindfoot
      instrument, whole-person assessment--the Short Form 36 (SF-36). RESULTS: Thirty
      eight patients were followed an average of 32 months (range, 12-48 months). Mean
      fracture healing time was 21 weeks (range, 9-60 weeks). Acceptable alignment and
      length were restored (angulation <or=5 degrees or shortening <or=1 cm) in all but
      one case. One patient (3%) had loss of fixation and two (5%) underwent secondary
      surgeries to achieve union. In 30 patients at >2 years, the AOFAS and the Olerud
      and Molander ankles scores averaged good-excellent. SF-36 outcomes scores were
      lower than that of normative data in patients with uninjured limbs but only
      significantly diminished in physical function. CONCLUSIONS: Minimally invasive
      medial plating using a hybrid locking plate technique in metaphyseal fractures of
      the distal tibia predictably restored limb alignment with a 5% reoperation rate
      and yielded mostly good-excellent ankle scores. There were residual impairments
      seen on whole-body outcomes measures.

PMID- 20035175
TI  - Extra-articular distal tibia fractures: a mechanical evaluation of 4 different
      treatment methods.
AB  - OBJECTIVE: This cadaveric biomechanical study compared the mechanical properties
      of standard plating (SP), locked plating (LP), intramedullary nailing (IMN), and
      angular stable intramedullary nailing (ASN) for the treatment of axially unstable
      distal tibia metaphyseal fractures (OTA type 43.A3) with an intact fibula.
      METHODS: A distal tibia metaphyseal fracture was created in 30 fresh frozen
      cadaveric specimens by performing an osteotomy 30 mm above the plafond. The
      fibula was left intact. Specimens were divided into 4 groups. Specimens underwent
      fracture fixation with a standard distal tibia plate, a medial locked plate, an
      intramedullary nail, or an angular stable intramedullary nail. Specimens were
      loaded vertically along the tibial axis to 700 N, followed by cyclical loading at
      700 N for 10,000 cycles, and then to failure. RESULTS: The IMN group demonstrated
      greater stiffness and load to failure than the LP group, which was greater than
      the SP group. The ASN group was not different in terms of stiffness and load to
      failure from the LP group for the number of specimens tested. The IM group
      required the greatest energy to failure, and all groups were significantly
      greater than the SP group. CONCLUSIONS: Under axial loading conditions with an
      intact fibula, both IMN and LP provide stable fixation. There was no advantage to
      the use of an ASN over a standard IMN. IMN resulted in the highest stiffness,
      load to failure, and failure energy for OTA type 43.A3 fractures with as little
      as 3 cm of distal bone stock.

PMID- 20035176
TI  - Use of the Reamer-Irrigator-Aspirator for bone graft harvest: a mechanical
      comparison of three starting points in cadaveric femurs.
AB  - OBJECTIVES: The mechanical behavior of cadaveric femurs after intramedullary
      reaming using the Reamer-Irrigator-Aspirator (RIA) for autogenous bone graft
      harvest has not been fully described. We hypothesized that reamed femurs,
      regardless of starting point, would adequately withstand cyclic loading
      simulating postoperative single-leg stance. METHODS: Twenty-one cadaveric pairs
      were randomly assigned to one of three groups based on starting point: Group 1
      (trochanteric), Group 2 (piriformis fossa), and Group 3 (retrograde). Each femur
      underwent dual-energy x-ray absorptiometry scanning and radiographs. Each test
      femur was reamed to 15 mm using the RIA with the contralateral femur serving as
      the control. The specimens were loaded to 1400 N of axial compression with 2
      degrees simultaneous torsion for 10,000 cycles. If the femur survived cyclic
      loading, it was then loaded to failure in axial compression. Comparisons
      regarding survival of cyclic loading were made using Fisher exact test. RESULTS:
      No differences were seen between groups regarding age, sex, and T-score. The mean
      T-score for the femurs was -2.531 +/- 1.372. Overall, 18 of 21 (86%) test femurs
      and 20 of 21 (95%) control femurs withstood cyclic loading (P = 0.606).
      Statistical significance was not reached for the three pairwise comparisons
      between test groups. The femurs failed in patterns consistent with simple
      pertrochanteric, basicervical, midcervical, or subcapital fractures. CONCLUSIONS:
      Intramedullary reaming for bone graft harvest using the RIA without subsequent
      intramedullary stabilization did not significantly degrade the mechanical
      behavior of cadaveric femurs in simulated single-leg stance regardless of reamer
      starting point. It appears safe to allow single-leg stance weightbearing on a
      reamed, unstabilized femur after bone graft harvesting using the RIA.

PMID- 20035177
TI  - Technical tricks when using the reamer irrigator aspirator technique for
      autologous bone graft harvesting.
AB  - This report describes technical tricks for using the reamer irrigator aspirator
      to harvest autologous bone graft from the femur. This device is a focus of
      interest in orthopaedics because it can be used to harvest bone graft from the
      femoral canal and medial condyle in voluminous quantities. Moreover, according to
      some authors, the osteogenic potential of this graft is at least as effective as
      that of autogenous bone obtained from the iliac crest. The reamer irrigator
      aspirator device has substantially different design characteristics and
      technicalities compared with those of a standard reamer. First, a guidewire must
      be redirected into multiple areas, including the center of the distal femur and
      into both condyles, to harvest ample bone graft. This is accomplished by
      prebending the guidewire in a stronger fashion than required for regular reaming
      in the case of femoral nailing procedures. This bend can increase the risk for
      eccentric reaming as well as lodging of the suctioning device within the femoral
      canal. Second, the front and lateral drilling surfaces of this device are very
      sharp and further cleaned and maintained sharp by the irrigation process to
      permit the surgeon to obtain significant volumes of graft with a single passage
      of this device. At the same time, however, this sharp front-end cutting design
      can increase the risk of iatrogenic fracture if reaming is performed without
      caution. Third, a powerful suctioning device is connected to the reamer such that
      the blood loss that can occur during continuous reaming, irrigation, and
      aspiration must be considered with this technique. We hereby discuss these
      potential dangers and describe the correct use of this device with technical
      tricks to minimize the risk of unexpected intraoperative events.

PMID- 20035178
TI  - Complications associated with negative pressure reaming for harvesting autologous
      bone graft: a case series.
AB  - A technical benefit of the reamer-irrigator-aspirator (RIA) system (Synthes,
      Paoli, PA) is the ability to harvest large volumes (40-90 cm3) of autogenous bone
      graft. Early evaluations of this technique have reported few problems, all of
      which were attributed to technical error. This case series reviews 6 RIA
      associated complications including 4 fractures and their contributing risk
      factors. Cases were collected from 4 independent orthopaedic centers, and all
      patients underwent RIA bone graft harvesting in a lower extremity long bone
      injuries. In this population, 2 patients experienced acute RIA-associated events,
      necessitating an additional procedure or altered postoperative rehabilitation,
      whereas 4 patients fractured through their donor site in the early postoperative
      period. This series suggests that surgeons should (1) preoperatively assess
      cortical diameters at long bone harvest sites, (2) carefully monitor
      intraoperative reaming, and (3) avoid RIA bone graft harvesting in patients with
      a history of osteoporosis or osteopenia unless postharvest intramedullary
      stabilization is considered.

PMID- 20035179
TI  - Leading 20 at 20: top cited articles and authors in the Journal of Orthopaedic
      Trauma, 1987-2007.
AB  - OBJECTIVE: To determine the 20 most cited articles and authors in the Journal of
      Orthopaedic Trauma during the first 20 years of publication, 1987 to 2007.
      DESIGN: Review. METHODS: We used Web of Science "cited reference search" to
      determine the most cited articles originating in the Journal of Orthopaedic
      Trauma from 1987 to 2007, the first 20 years of publication. The characteristics
      of each article were recorded. Next, we manually searched each author's citations
      for works in the same time period to determine the most cited authors. The number
      of first authorships for each author was then determined using Medline, and a
      relative citation impact ratio was calculated. Finally, citation reports for the
      journal overall were created to evaluate the citation impact of the journal over
      the last 10 years. RESULTS: The top cited articles ranged from 64 to 566
      citations with two articles over 100. Fifteen were clinical articles with the
      most common topic being tibia fractures (shaft, plateau, and pilon). The top
      cited authors ranged for 111 to 566 citations, whereas the citations per lead
      authorship ratio for the authors on that list ranged from 9.5 to 566 citations
      per lead authorship. The number of citations to the Journal of Orthopaedic Trauma
      overall over the last 20 years has increased from 181 in 1997 to 3050 in 2007.
      CONCLUSIONS: The influence of the Journal of Orthopaedic Trauma, its articles,
      and its authors is readily apparent in this review of the most cited articles and
      authors in the journal over its first 20 years of publication. This journal is a
      source of highly cited original articles and the work of many highly cited
      leaders in the field of orthopaedic trauma.

PMID- 20035180
TI  - Re: Lessons learned from a case of proximal humeral locked plating gone awry.

PMID- 20035181
TI  - Re: Percutaneous humeral plating of fractures of the proximal humerus: results of
      a prospective multicenter clinical trial.

PMID- 20035183
TI  - D-lactic acidosis: "right-left disorientation" in laboratory testing: acute
      encephalopathy in a child with carbohydrate malabsorption syndrome.

PMID- 20035184
TI  - International thymic malignancy interest group.

PMID- 20035185
TI  - A novel histopathological evaluation method predicting the outcome of non-small
      cell lung cancer treated by neoadjuvant therapy: the prognostic importance of the
      area of residual tumor.
AB  - BACKGROUND: Histopathological evaluation method for predicting the outcome of non
      small cell lung cancer (NSCLC) treated by neoadjuvant therapy has not been fully
      assessed. The purpose of this study was to assess a novel histopathological
      evaluation method for predicting the outcome of NSCLC treated by neoadjuvant
      therapy. METHODS: We reviewed the histopathology of the tumors of 53 NSCLC
      treated by neoadjuvant chemotherapy, chemoradiotherapy, or radiotherapy followed
      by complete resection and identified the histologic features produced by
      neoadjuvant therapy by comparing them with the histologic features of the tumors
      in 138 NSCLC cases treated by surgery without neoadjuvant therapy. We also
      measured the area of residual tumor (ART) on the maximum cut surface of the
      tumors and analyzed the relationships between the histologic features, ART, and
      the outcome. RESULTS: The proportions of cases with the histologic features
      "cholesterin clefts," "foreign body reactive giant cells," "stromal hyalinosis,"
      and "bizarre nucleus in more than 50% of the cancer cells" were significantly
      higher in the neoadjuvant therapy group than in the surgery alone group. However,
      the presence of none of these features had any significant effect on survival.
      Although pathologic T factor and N factor had no significant effect on overall
      survival, smaller ART (< or =400 mm) and absence of pleural invasion (p [-]) were
      predictors of a outcome (p = 0.014 and p = 0.003, respectively). CONCLUSIONS:
      Smaller ART and p (-) predict a better outcome of NSCLC treated by neoadjuvant
      therapy. We concluded that ART is a novel histopathological evaluation method for
      predicting the outcome of NSCLC treated by neoadjuvant therapy.

PMID- 20035186
TI  - A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and
      conformal three-dimensional thoracic radiation followed by consolidative
      docetaxel and maintenance gefitinib for patients with stage III non-small cell
      lung cancer.
AB  - BACKGROUND: Concurrent radiation and chemotherapy is the standard of care for
      good performance status patients with stage III non-small cell lung cancer.
      Locoregional control remains a significant factor relating to poor outcome.
      Preclinical and early clinical data suggest that docetaxel and gefitinib have
      radiosensitizing activity. This study sought to define the maximum tolerated dose
      of weekly docetaxel that could be given with daily gefitinib and concurrent
      thoracic radiation therapy. PATIENTS AND MATERIALS: Patients with histologically
      confirmed, inoperable stage III non-small cell lung cancer and good performance
      status (Eastern Cooperative Oncology Group 0-1) were eligible for this study.
      Patients received three-dimensional conformal thoracic radiation to a dose of 70
      Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous,
      weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients.
      Patients were given a 2-week rest period after the concurrent therapy, during
      which they received only gefitinib. After the 2-week rest period, patients
      received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days
      for two cycles. Maintenance gefitinib was continued until disease progression or
      study completion. RESULTS: Sixteen patients were enrolled on the study between
      December 2003 and April 2007 with the following characteristics: median age, 64
      years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose
      limiting pulmonary toxicity and esophagitis were encountered at a weekly
      docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk.
      Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade
      3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients,
      respectively. The overall response rate was 46%, and the median survival for all
      patients was 21 months. CONCLUSIONS: Concurrent thoracic radiation with weekly
      docetaxel and daily gefitinib is feasible but results in moderate toxicity. For
      further studies, the recommended weekly docetaxel dose for this chemoradiation
      regimen is 20 mg/m2.

PMID- 20035187
TI  - Outcomes associated with brain metastases in a three-arm phase III trial of
      gemcitabine-containing regimens versus paclitaxel plus carboplatin for advanced
      non-small cell lung cancer.
AB  - BACKGROUND: Brain metastases (BMs) are a common complication of non-small cell
      lung cancer (NSCLC). Because of historical data indicating a poor prognosis for
      patients with BM, few randomized phase III studies of advanced NSCLC have
      included patients with BM at presentation. Because the potential benefits of
      systemic therapy in patients with BM are uncertain, we analyzed data from a
      recent phase III study. METHODS: One thousand one hundred thirty-five chemonaive
      patients with stage IIIB/IV NSCLC were randomized to receive
      gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin.
      Stratification was based on presence or absence of BM, stage, and baseline weight
      loss. Patients with BM were required to be clinically stable after treatment with
      radiotherapy or surgery before entry. Results were retrospectively analyzed by
      presence or absence of BM at study entry. RESULTS: Rate of BM was 17.1% overall.
      The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without
      BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without
      BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3)
      among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9
      9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse
      events were not different among patients with and without BM. CONCLUSIONS: There
      were no significant differences in response, survival, or hematologic toxicity
      for patients with or without BM; however, patients with BM had a small but
      significantly shorter time to progression. Nonprogressing patients with treated
      BM are appropriate candidates for systemic therapy and entry into clinical
      trials.

PMID- 20035189
TI  - Image of the month. Pericardial varices secondary to superior vena cava
      obstruction.

PMID- 20035188
TI  - Synchronous pulmonary renal cell carcinoma metastases and primary non-small cell
      lung cancer.

PMID- 20035190
TI  - Image of the month. A hole in the heart.

PMID- 20035191
TI  - Autofluorescence imaging is still valuable even in the presence of a peripheral
      lung lesion.

PMID- 20035192
TI  - The blueprint to excellence.

PMID- 20035193
TI  - Solving the critical thinking puzzle.

PMID- 20035194
TI  - Nursing in the era of "meaningful use".

PMID- 20035195
TI  - Another look: best practices for pressure ulcer prevention.

PMID- 20035196
TI  - Partnering with palliative care.

PMID- 20035198
TI  - Nurse leaders: a closer look.

PMID- 20035199
TI  - From Wall Street, to Main Street... to your hospital.

PMID- 20035200
TI  - Nurses and computerized systems: is "hands-on" most helpful?

PMID- 20035201
TI  - Visionary leader 2009: Deborah Kumar.
AB  - The following manuscript is the winning Visionary Leader 2009 entry submitted to
      Nursing Management in recognition of Deborah Kumar, MSN, RN, NEA-BC, Director,
      Medical Division, The Reading Hospital and Medical Center, West Reading, Pa.
      Deborah was formally recognized for her achievements during the opening ceremony
      of Congress 2009, September 9, in Chicago, Ill. There, she received the award,
      sponsored this year by B.E. Smith.

PMID- 20035202
TI  - 7 tips to improve your professional etiquette.

PMID- 20035203
TI  - Using CCTA to rule out coronary artery disease.

PMID- 20035204
TI  - Resolving conflict--now more important than ever.

PMID- 20035205
TI  - Road signs along the career continuum.

PMID- 20035207
TI  - Randomized trial to assess immunogenicity and safety of Haemophilus influenzae
      type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate
      vaccine in infants.
AB  - BACKGROUND: Study assessed the immunogenicity and safety of an investigational
      Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus
      toxoid conjugate vaccine (HibMenCY-TT) in infants. METHODS: In a single-blinded,
      controlled study, 609 infants were randomized 1:1 to receive primary vaccination
      (2, 4, and 6 months) with either HibMenCY-TT or monovalent Haemophilus influenzae
      type b tetanus toxoid conjugate vaccine (Hib-TT), co-administered with combined
      diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine
      and 7-valent pneumococcal conjugate vaccine. A second control group of 3- to 5
      year-old children received a single dose of licensed meningococcal ACWY
      polysaccharide vaccine (MPSV4). Immunogenicity was measured before and 1 month
      after dose 3/MPSV4 using human (hSBA) and rabbit complement bactericidal assays
      (rSBA) and enzyme-linked immunosorbent assay assays for IgG antibodies to MenC
      and MenY polysaccharides. Anti-polyribosylribitol phosphate antibody
      concentrations were measured 1 month after the third dose. Safety was also
      assessed. RESULTS: One month after primary vaccination statistically
      significantly more HibMenCY-TT than Hib-TT vaccines had anti-PRP antibody
      concentrations > or =1.0 microg/mL (93.5% vs. 85.8%). The percentage of HibMenCY
      TT recipients with hSBA titers > or =1:8 (MenC: 95.9%, MenY: 89.4%) was
      statistically significantly higher than for MPSV4 recipients (MenC: 30.2%, MenY:
      47.5%). The percentage of subjects reporting any severe (grade 3) symptom within
      4 days of each vaccination was: 11.5% (HibMenCY-TT) and 24.8% (Hib-TT) (group
      difference, 13.27%, 95% CI: [7.22;19.29], P < 0.001). CONCLUSION: The
      investigational HibMenCY-TT vaccine was well tolerated and immunogenic in
      infants, induced Hib immune responses that were comparable to licensed Hib-TT
      vaccine, and induced high levels of bactericidal antibodies against N.
      meningitidis serogroups C and Y.

PMID- 20035208
TI  - Carbapenemases: a brief review for pediatric infectious disease specialists.

PMID- 20035209
TI  - Angiostrongylus cantonensis meningitis in two developmentally delayed children:
      findings in brain images.

PMID- 20035210
TI  - Unusual cases of meningitis as a clue to the diagnosis of Currarino Syndrome.

PMID- 20035211
TI  - Prevention of rheumatic fever.

PMID- 20035212
TI  - Excessive menstrual bleeding in adolescents with dengue infection.

PMID- 20035214
TI  - No evidence of mother-to-infant transmission of human papilloma virus via human
      breast milk.

PMID- 20035215
TI  - Treatment of acute sinusitis.

PMID- 20035216
TI  - Nonventilatory strategies for patients with life-threatening 2009 H1N1 influenza
      and severe respiratory failure.
AB  - Severe respiratory failure (including acute lung injury and acute respiratory
      distress syndrome) caused by 2009 H1N1 influenza infection has been reported
      worldwide. Refractory hypoxemia is a common finding in these patients and can be
      challenging to manage. This review focuses on nonventilatory strategies in the
      advanced treatment of severe respiratory failure and refractory hypoxemia such as
      that seen in patients with severe acute respiratory distress syndrome
      attributable to 2009 H1N1 influenza. Specific modalities covered include
      conservative fluid management, prone positioning, inhaled nitric oxide, inhaled
      vasodilatory prostaglandins, and extracorporeal membrane oxygenation and life
      support. Pharmacologic strategies (including steroids) investigated for the
      treatment of severe respiratory failure are also reviewed.

PMID- 20035217
TI  - Risk factors and outcome of transfusion-related acute lung injury in the
      critically ill: a nested case-control study.
AB  - OBJECTIVES: To determine the incidence, risk factors, and outcome of transfusion
      related acute lung injury in a cohort of critically ill patients. DESIGN: In a
      retrospective cohort study, patients with transfusion-related acute lung injury
      were identified using the consensus criteria of acute lung injury within 6 hrs
      after transfusion. Inclusion criterion was a length of intensive care unit
      admission >48 hrs. Patients developing transfusion-related acute lung injury were
      matched (on age, sex, and admission diagnosis) to transfused control subjects and
      patients developing acute lung injury from another origin. SETTING: Tertiary
      referral hospital. PATIENTS: All first-admitted patients from November 1, 2004,
      until October 1, 2007, to the intensive care unit. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Of 5208 admitted patients, 2024 patients had a
      length of stay >48 hrs, of whom 109 were suspected transfusion-related acute lung
      injury cases. Compared with transfused control subjects, risk factors for
      transfusion-related acute lung injury were emergency cardiac surgery (odds ratio,
      17.6 [1.8-168.5]), hematologic malignancy (odds ratio, 13.1 [2.7-63.8]), massive
      transfusion (odds ratio, 4.5 [2.1-9.8]), sepsis (odds ratio, 2.5 [1.2-5.2]),
      mechanical ventilation (odds ratio, 3.0 [1.3-7.1], and high Acute Physiology and
      Chronic Health Evaluation II score (odds ratio, 1.1 [1.0-1.1]; p < .03 for all).
      The volume of platelets and plasma transfused was associated with transfusion
      related acute lung injury in the univariate analysis. However, this association
      disappeared in the multivariate analysis. Compared with acute lung injury control
      subjects, risk factors for transfusion-related acute lung injury were sepsis
      (odds ratio, 2.4 [1.1-5.3]) and high Acute Physiology and Chronic Health
      Evaluation II score (odds ratio, 1.1 [1.0-1.1]), whereas pneumonia (odds ratio,
      0.4 [0.2-0.7]) was a negative predictive factor. Patients with transfusion
      related acute lung injury had a longer duration of mechanical ventilation
      compared with transfused control subjects and acute lung injury control subjects
      (231 [138-472] vs. 71 [46-163] and 70 [42-121] hrs, p < .001). Also, 90-day
      survival of patients with transfusion-related acute lung injury was lower
      compared with transfused control subjects and acute lung injury control subjects
      (53% vs. 75% and 83%, p < .02). CONCLUSIONS: Transfusion-related acute lung
      injury is common in critically ill patients. Transfusion-related acute lung
      injury may contribute to an adverse outcome associated with transfusion. This
      study identifies transfusion-related acute lung injury risk factors, which may
      aid in assessing the risks and benefits of transfusion in critically ill
      patients.

PMID- 20035218
TI  - Glucose variability is associated with intensive care unit mortality.
AB  - OBJECTIVE: Mounting evidence suggests a role for glucose variability in
      predicting intensive care unit (ICU) mortality. We investigated the association
      between glucose variability and intensive care unit and in-hospital deaths across
      several ranges of mean glucose. DESIGN: Retrospective cohort study. SETTING: An
      18-bed medical/surgical ICU in a teaching hospital. PATIENTS: All patients
      admitted to the ICU from January 2004 through December 2007. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Two measures of variability, mean absolute glucose
      change per hour and sd, were calculated as measures of glucose variability from
      5728 patients and were related to ICU and in-hospital death using logistic
      regression analysis. Mortality rates and adjusted odds ratios for ICU death per
      mean absolute glucose change per hour quartile across quartiles of mean glucose
      were calculated. Patients were treated with a computerized insulin algorithm
      (target glucose 72-126 mg/dL). Mean age was 65 +/- 13 yrs, 34% were female, and
      6.3% of patients died in the ICU. The odds ratios for ICU death were higher for
      quartiles of mean absolute glucose change per hour compared with quartiles of
      mean glucose or sd. The highest odds ratio for ICU death was found in patients
      with the highest mean absolute glucose change per hour in the upper glucose
      quartile: odds ratio 12.4 (95% confidence interval, 3.2-47.9; p < .001).
      Mortality rates were lowest in the lowest mean absolute glucose change per hour
      quartiles. CONCLUSIONS: High glucose variability is firmly associated with ICU
      and in-hospital death. High glucose variability combined with high mean glucose
      values is associated with highest ICU mortality. In patients treated with strict
      glycemic control, low glucose variability seemed protective, even when mean
      glucose levels remained elevated.

PMID- 20035219
TI  - The Surviving Sepsis Campaign: results of an international guideline-based
      performance improvement program targeting severe sepsis.
AB  - OBJECTIVE: The Surviving Sepsis Campaign (SSC or "the Campaign") developed
      guidelines for management of severe sepsis and septic shock. A performance
      improvement initiative targeted changing clinical behavior (process improvement)
      via bundles based on key SSC guideline recommendations. DESIGN AND SETTING: A
      multifaceted intervention to facilitate compliance with selected guideline
      recommendations in the intensive care unit, emergency department, and wards of
      individual hospitals and regional hospital networks was implemented voluntarily
      in the United States, Europe, and South America. Elements of the guidelines were
      "bundled" into two sets of targets to be completed within 6 hrs and within 24
      hrs. An analysis was conducted on data submitted from January 2005 through March
      2008. SUBJECTS: A total of 15,022 subjects. MEASUREMENTS AND MAIN RESULTS: Data
      from 15,022 subjects at 165 sites were analyzed to determine the compliance with
      bundle targets and association with hospital mortality. Compliance with the
      entire resuscitation bundle increased linearly from 10.9% in the first site
      quarter to 31.3% by the end of 2 yrs (p < .0001). Compliance with the entire
      management bundle started at 18.4% in the first quarter and increased to 36.1% by
      the end of 2 yrs (p = .008). Compliance with all bundle elements increased
      significantly, except for inspiratory plateau pressure, which was high at
      baseline. Unadjusted hospital mortality decreased from 37% to 30.8% over 2 yrs (p
      = .001). The adjusted odds ratio for mortality improved the longer a site was in
      the Campaign, resulting in an adjusted absolute drop of 0.8% per quarter and 5.4%
      over 2 yrs (95% confidence interval, 2.5-8.4). CONCLUSIONS: The Campaign was
      associated with sustained, continuous quality improvement in sepsis care.
      Although not necessarily cause and effect, a reduction in reported hospital
      mortality rates was associated with participation. The implications of this study
      may serve as an impetus for similar improvement efforts.

PMID- 20035220
TI  - Secondhand smoke at work.
AB  - PURPOSE OF REVIEW: Secondhand smoke (SHS) exposure in the workplace remains
      common and has important acute and chronic health effects. The present study
      reviews the recent evidence linking workplace SHS exposure with poor health and
      the benefits of smoke-free workplace legislation. RECENT FINDINGS: Workplace SHS
      exposure continues to occur in many parts of the United States and around the
      world. Occupational SHS exposure has been linked to serious chronic health
      effects including lung cancer, cardiovascular disease, chronic obstructive
      pulmonary disease, and poor general health. Smoke-free workplace laws rapidly
      reduce workplace SHS exposure and improve respiratory health including symptoms
      and lung function. Smoke-free workplace legislation is also expected to reduce
      the chronic health effects of passive smoking, including cardiopulmonary disease
      and lung cancer. SUMMARY: Occupational exposure to SHS has serious negative
      health consequences and will shorten lifespan. Smoke-free workplace legislation
      should be universally adopted around the world.

PMID- 20035221
TI  - Lung function measurement in the assessment of childhood asthma: recent important
      developments.
AB  - PURPOSE OF REVIEW: To present three clinically important developments related to
      the utilization of pulmonary function to objectively assess the asthmatic child.
      RECENT FINDINGS: The new asthma guidelines (2007) have added the forced
      expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio to the FEV1 as
      spirometric criteria for classifying asthma. Although a better indicator of
      airway obstruction, it has not clearly been shown to correlate with clinical
      criteria. The normal cut point for the ratio used in the guidelines of 85% for
      children may be too high, and compared to the lower limits of normal of 80%,
      could result in unnecessary treatment in some children. The bronchodilator
      response (BDR) phenotype reflects airway lability and has been associated with
      biomarkers of inflammation and responsiveness to inhaled corticosteroids as well
      as predicting long-term outcomes. Several studies have shown improved spirometric
      techniques in preschoolers as well as defining normal values in this age group.
      Impulse oscillometry (IOS), which is less demanding than spirometry, has been
      shown to identify asthmatic preschoolers in some cases better than spirometry and
      possibly identifying obstruction in the peripheral airways. It may also be a more
      useful test than spirometry in evaluating long-term drug studies. SUMMARY: In
      addition to the FEV1/FVC ratio to detect airway obstruction, the BDR phenotype
      would appear to give important additional information regarding airway lability
      and inflammation, and should be included as routine spirometry. IOS is a
      promising test to identify asthmatic preschoolers, but more studies are needed to
      determine exactly what it measures and what constitutes normal values.

PMID- 20035222
TI  - Role of bracing in the management of knee osteoarthritis.
AB  - PURPOSE OF REVIEW: Recommendations for nonpharmacological treatment for knee
      osteoarthritis are based mainly on modifying the symptomatic loading joint
      compartment. Braces are one of the modalities used to modify joint loading. Knee
      osteoarthritis braces consist of rest orthoses, knee sleeves, and unloading-knee
      braces. This review examines the most recent publications regarding the various
      bracing modalities proposed for different knee osteoarthritis compartments.
      RECENT FINDINGS: The effectiveness of rest orthoses for lower-limb osteoarthritis
      has not been studied in clinical trials. Knee sleeves are elastic nonadhesive
      orthoses associated with various devices aimed at patellar or femoro-tibial
      stabilization. They may decrease knee pain. Unloading-knee braces are functional
      devices composed of external stems, hinges, and straps. Several recent
      biomechanical studies have established the effectiveness of modifying loading
      with unloading-knee braces. Such braces may decrease knee pain, and improve knee
      function. SUMMARY: Braces are recommended for treating knee osteoarthritis. The
      different bracing modalities that are available must be adapted to the
      symptomatic knee osteoarthritis compartment. This nonpharmacological approach
      must be added to the other nonpharmacological, and pharmacological modalities to
      decrease pain and improve function and thereby increase the quality of life of
      osteoarthritis patients. The structural effect of bracing has not yet been
      evaluated. High-quality clinical trials of the addition of various treatment
      modalities for knee osteoarthritis are still necessary.

PMID- 20035223
TI  - Genetics research in systemic lupus erythematosus for clinicians: methodology,
      progress, and controversies.
AB  - PURPOSE OF REVIEW: Clinical journals are reporting genetic associations with
      systemic lupus erythematosus (SLE) with increasing frequency. Interpreting these
      studies is difficult for clinicians without rigorous training in epidemiology,
      statistics, and genetics. In this review, we discuss basic issues important to
      understanding and contextualizing new genetic association studies. We, therefore,
      highlight literature related to methodology as well as recent genetic discoveries
      in SLE. RECENT FINDINGS: Functional single nucleotide polymorphisms (SNPs) and/or
      haplotypes have now been identified for ITGAM, PTPN22, and IRF5, and several
      additional loci have been highlighted in recent genome-wide association studies
      in SLE. Recent work also indicates that several regions within the extended major
      histocompatibility complex contribute independently to SLE risk. Evidence of
      additive statistical interaction has been found between IRF5 and TYK2, IRF5, and
      STAT4, and between NAT2 and exposure to tobacco smoke. SUMMARY: Many new genes
      have been associated with SLE susceptibility, revealing insight into SLE
      pathophysiology. Current research is focusing on further refining the initial
      genetic association results and extending this work to non-European populations.
      Research is also expanding beyond SNP associations to investigate the
      contribution of copy number variants (CNVs) and DNA methylation to SLE risk.

PMID- 20035224
TI  - Unusual clinical presentations of gout.
AB  - PURPOSE OF REVIEW: The dogmatic description of gout is described as an
      inflammatory crystal-induced arthropathy that afflicts peripheral joints. This
      manuscript describes many recent cases and unusual clinical presentations of
      gout. Emphasis is placed on the ability of gout to cause diagnostic dilemmas that
      can impact patient treatment and care. RECENT FINDINGS: Various genetic mutations
      can predispose patients in developing early onset gout. Environmental exposures,
      medications, and certain patient populations can affect pathophysiology of uric
      acid, predisposing patients both typical and atypical manifestations of gout.
      Numerous reports have described gout deposition in unusual parts of the body,
      which can mimic unrelated disease processes. SUMMARY: Although classic gout is
      still most commonly seen, the disease can manifest as with a wide array of
      presentations. It is likely that such atypical presentations are a result of a
      complexity of reasons. When presented with a diagnostic challenge in a patient
      with gout, the clinician should be aware of unusual manifestations of gout and
      consider it in the differential.

PMID- 20035225
TI  - A prescription for lifestyle change in patients with hyperuricemia and gout.
AB  - PURPOSE OF REVIEW: This review summarizes the recent data on lifestyle factors
      that influence serum uric acid levels and the risk of gout and attempts to
      provide holistic recommendations, considering both their impact on gout as well
      as on other health implications. RECENT FINDINGS: Large-scale studies have
      clarified a number of long-suspected relations between lifestyle factors,
      hyperuricemia, and gout, including purine-rich foods, dairy foods, various
      beverages, fructose, and vitamin C supplementation. Furthermore, recent studies
      have identified the substantial burden of comorbidities among patients with
      hyperuricemia and gout. SUMMARY: Lifestyle and dietary recommendations for gout
      patients should consider overall health benefits and risk, since gout is often
      associated with the metabolic syndrome and an increased future risk of
      cardiovascular disease (CVD) and mortality. Weight reduction with daily exercise
      and limiting intake of red meat and sugary beverages would help reduce uric acid
      levels, the risk of gout, insulin resistance, and comorbidities. Heavy drinking
      should be avoided, whereas moderate drinking, sweet fruits, and seafood intake,
      particularly oily fish, should be tailored to the individual, considering their
      anticipated health benefits against CVD. Dairy products, vegetables, nuts,
      legumes, fruits (less sugary ones), and whole grains are healthy choices for the
      comorbidities of gout and may also help prevent gout by reducing insulin
      resistance. Coffee and vitamin C supplementation could be considered as
      preventive measures as these can lower urate levels, as well as the risk of gout
      and some of its comorbidities.

PMID- 20035226
TI  - Sevoflurane-emergence agitation: effect of supplementary low-dose oral ketamine
      premedication in preschool children undergoing dental surgery.
AB  - BACKGROUND AND OBJECTIVE: The use of sevoflurane in paediatric anaesthesia which
      could enable rapid recovery is complicated by the frequent occurrence of
      emergence agitation. The aim of this study was to test the efficacy of
      supplementing midazolam-based oral premedication with low-dose oral ketamine in
      reducing sevoflurane-related emergence agitation. METHODS: Ninety-two healthy
      preschool children who have been scheduled for elective dental procedures under
      general anaesthesia were allocated into two groups (46 patients for each): group
      M received oral midazolam 0.5 mg kg(-1), whereas group KM received similar
      premedication in addition to ketamine 2 mg kg(-1). Acceptance of drug mixture and
      onset of action were monitored over the next 30 min. Induction of anaesthesia was
      carried out using sevoflurane 8 vol% in 100% oxygen via face mask. Anaesthesia
      was maintained with sevoflurane 1.5-2 vol% in oxygen-nitrous oxide mixture.
      Following extubation, standard scoring scale was used for assessing quality of
      emergence. Agitation parameters were measured using a five-point scale. Agitated
      children were managed by giving intravenous increments of fentanyl 1 microg kg(
      1). The time of hospital discharge allowance was recorded. RESULTS: Vast majority
      of children accepted the premedication. There were no significant differences
      between both groups regarding recovery from sevoflurane and allowance of hospital
      discharge. Onset of action of premedication was shorter in group KM. Similarly,
      postoperative agitation score and rescue fentanyl consumption were markedly lower
      in group KM upon admission to the postanaesthesia care unit (P<0.01). CONCLUSION:
      Adding a low dose of oral ketamine to midazolam-based oral premedication in
      preschool children undergoing dental surgery reduced emergence agitation without
      delaying hospital discharge.

PMID- 20035227
TI  - Spontaneous ventilation to monitor brainstem perfusion: an old concept revisited.

PMID- 20035228
TI  - Accuracy of stroke volume variation compared with pleth variability index to
      predict fluid responsiveness in mechanically ventilated patients undergoing major
      surgery.
AB  - BACKGROUND AND OBJECTIVE: Accurate assessment of a patient's volume status is an
      important goal for an anaesthetist. However, most variables assessing fluid
      responsiveness are either invasive or technically challenging. This study was
      designed to compare the accuracy of arterial pressure-based stroke volume
      variation (SVV) and variations in the pulse oximeter plethysmographic waveform
      amplitude as evaluated with the noninvasive calculated pleth variability index
      (PVI) with central venous pressure to predict the response of stroke volume index
      (SVI) to volume replacement in patients undergoing major surgery. METHODS: We
      studied 20 patients scheduled for elective major abdominal surgery. After
      induction of anaesthesia, all haemodynamic variables were recorded immediately
      before (T1) and subsequent to volume replacement (T2) by infusion of 6% hydroxy
      ethyl starch (HES) 130/0.4 (7 ml kg) at a rate of 1 ml kg min. RESULTS: The
      volume-induced increase in SVI was at least 15% in 15 patients (responders) and
      less than 15% in five patients (nonresponders). Baseline SVV correlated
      significantly with changes in SVI (DeltaSVI; r = 0.80; P < 0.001) as did baseline
      PVI (r = 0.61; P < 0.004), whereas baseline values of central venous pressure
      showed no correlation to DeltaSVI. There was no significant difference between
      the area under the receiver operating characteristic curve for SVV (0.993) and
      PVI (0.973). The best threshold values to predict fluid responsiveness were more
      than 11% for SVV and more than 9.5% for PVI. CONCLUSION: Although arterial
      pressure-derived SVV revealed the best correlation to volume-induced changes in
      SVI, the results of our study suggest that both variables, SVV and PVI, can serve
      as valid indicators of fluid responsiveness in mechanically ventilated patients
      undergoing major surgery.

PMID- 20035229
TI  - Bispectral index variations in patients with neurological deficits during awake
      carotid endarterectomy.
AB  - BACKGROUND AND OBJECTIVE: The bispectral index (BIS) is derived from the EEG and
      therefore may be useful to diagnose intraoperative cerebral ischaemia. This study
      was undertaken to investigate BIS changes in awake patients with and without
      neurological deficits during carotid endarterectomy under regional anaesthesia.
      METHODS: Seventy consecutive carotid endarterectomies under regional anaesthesia
      were divided into two surgical groups: patients with and patients without
      neurological deficits. Patients' neurological status was evaluated and
      neurological deficits were compared with BIS values. Measurements were made at
      different surgical stages: baseline, after sedation, at the beginning of surgery,
      at preclamping, at the 3 min clamping test, during shunt insertion, at
      declamping, 15 min after declamping and at the end of surgery. We performed
      intergroup and intragroup comparisons of BIS values. A decrease in BIS of at
      least 10 associated with neurological deficits was taken as the cut-off point for
      the classification of patients with logistic regression models (crude and
      adjusted for potential confounders). RESULTS: Thirteen patients (18.6% of the
      total) developed clinical cerebral ischaemia, though BIS values decreased in 10
      of these patients (76.9%). The mean BIS values were 92.5+/-5.6 and 84.7+/-12.3
      for patients without and with neurological deficits, respectively (P value<0.05).
      The odds ratios of a BIS decrease associated with neurological deficits were 8.5
      (95% confidence interval 2.1-35.1) and 5.4 (95% confidence interval 1.2-24.3)
      adjusted for contralateral stenosis. CONCLUSION: Our results describe a
      relationship between BIS reductions and neurological deficits during carotid
      surgery in awake patients.

PMID- 20035230
TI  - Platelet function recovery after cessation of aspirin: preliminary study of
      volunteers and surgical patients.
AB  - BACKGROUND AND OBJECTIVE: Recent evidence indicates that platelet function may
      recover more rapidly after cessation of aspirin therapy than previously thought.
      The present study evaluated the effect of aspirin on platelet function using
      platelet aggregometry in healthy individuals and in aspirin-treated patients
      scheduled for surgery. METHODS: Platelet aggregation in response to arachidonic
      acid, epinephrine, and adenosine diphosphate was determined in 14 male volunteers
      during and after 10 days' aspirin administration (100 mg) and in 58 aspirin
      treated patients during intake, on days 3, 4 or 6 after drug cessation, and on
      day 10 after drug cessation, prior to elective surgery. Urine thromboxane (11
      dehydro-thromboxane B2) concentrations were also measured. RESULTS: Platelet
      aggregation in response to arachidonic acid and epinephrine was significantly
      decreased in both volunteers and patients during aspirin administration. The
      aggregation normalized within 3 days of aspirin cessation in the volunteers and
      within 4-6 days in the patients. Urine concentration of 11-dehydro-thromboxane B2
      was about three times lower with aspirin treatment than without, although in two
      patients concentrations were higher with aspirin. CONCLUSION: Platelet
      aggregometry with arachidonic acid is a sensitive test for the evaluation of the
      effects of aspirin on platelet function. In most aspirin-treated patients,
      platelet function recovers 4 days after drug cessation, although the process is
      sometimes prolonged. Therefore, the time of aspirin cessation before scheduled
      surgery should be determined individually.

PMID- 20035231
TI  - Longitudinal analysis of patterns and predictors of changes in self-reported
      adherence to antiretroviral therapy: Swiss HIV Cohort Study.
AB  - BACKGROUND: Adherence to combination antiretroviral therapy (cART) is a dynamic
      process, however, changes in adherence behavior over time are insufficiently
      understood. METHODS: Data on self-reported missed doses of cART was collected
      every 6 months in Swiss HIV Cohort Study participants. We identified behavioral
      groups associated with specific cART adherence patterns using trajectory
      analyses. Repeated measures logistic regression identified predictors of changes
      in adherence between consecutive visits. RESULTS: Six thousand seven hundred nine
      individuals completed 49,071 adherence questionnaires [median 8 (interquartile
      range: 5-10)] during a median follow-up time of 4.5 years (interquartile range:
      2.4-5.1). Individuals were clustered into 4 adherence groups: good (51.8%),
      worsening (17.4%), improving (17.6%), and poor adherence (13.2%). Independent
      predictors of worsening adherence were younger age, basic education, loss of a
      roommate, starting intravenous drug use, increasing alcohol intake, depression,
      longer time with HIV, onset of lipodystrophy, and changing care provider.
      Independent predictors of improvements in adherence were regimen simplification,
      changing class of cART, less time on cART, and starting comedications.
      CONCLUSIONS: Treatment, behavioral changes, and life events influence patterns of
      drug intake in HIV patients. Clinical care providers should routinely monitor
      factors related to worsening adherence and intervene early to reduce the risk of
      treatment failure and drug resistance.

PMID- 20035232
TI  - HIV risk behavior before and after HIV counseling and testing in jail: a pilot
      study.
AB  - OBJECTIVES: Jail incarceration represents an opportunity to deliver HIV
      counseling and testing (C&T) services to persons at increased risk of infection.
      However, jails can be chaotic with rapid turnover of detainees. We conducted a
      pilot study to investigate the feasibility of comparing the effect of different
      approaches to HIV C&T in jail on subsequent HIV risk behaviors among persons
      testing HIV negative. METHODS: Consecutive cohorts of newly incarcerated jail
      detainees were recruited with 132 subjects completing standard HIV C&T as per
      jail protocol and 132 subjects completing rapid testing with an individualized
      counseling session. Risk behavior was assessed and compared at baseline and 6
      weeks after jail release. RESULTS: Among the 264 male participants,
      preincarceration substance use and sexual risk were common. The follow-up visit
      was completed by 59% of eligible participants. There were no differences in
      postrelease HIV risk behavior between the 2 arms but there was an overall
      decrease in risk behavior after jail release for the cohort. In addition, all
      participants in the rapid arm received rapid HIV test results compared with
      participants receiving 28% of conventional test results. CONCLUSIONS: Jail
      incarceration represents an important public health opportunity to deliver HIV
      C&T. This study demonstrated (1) feasibility in delivering rapid HIV testing
      combined with individualized counseling to jail detainees, (2) improved test
      result delivery rates, and (3) success with evaluating risk behaviors during the
      transition from jail to the community. Further research is needed to determine
      the optimal approach to HIV C&T in jail with the goal of increasing awareness of
      HIV serostatus and decreasing HIV risk behavior.

PMID- 20035233
TI  - Can pulmonary artery hypertension be attributed to levosimendan? A problematic
      based on a patient's case.

PMID- 20035234
TI  - Successful high-risk percutaneous coronary revascularization using Impella
      Recover LP 5.0 l/min.

PMID- 20035235
TI  - National hospital quality measures data: supporting nurses' key roles in
      organizational performance improvement.
AB  - With the emergence of so many methodologies for generating comparison data and
      with the growing accountability demands from so many sectors (each, seemingly,
      with its own preferred comparative methodology), nurses and quality improvement
      professionals may feel as if they have many masters to serve. This article
      outlines the Maryland Hospital Association's Quality Indicator Project's approach
      to working with quality improvement professionals to build their understanding of
      comparative data and help them determine which data analysis tools best fit their
      reporting needs.

PMID- 20035236
TI  - Simulating school closure strategies to mitigate an influenza epidemic.
AB  - BACKGROUND: There remains substantial debate over the impact of school closure as
      a mitigation strategy during an influenza pandemic. The ongoing 2009 H1N1
      influenza pandemic has provided an unparalleled opportunity to test interventions
      with the most up-to-date simulations. METHODS: To assist the Allegheny County
      Health Department during the 2009 H1N1 influenza pandemic, the University of
      Pittsburgh Models of Infectious Disease Agents Study group employed an agent
      based computer simulation model (ABM) of Allegheny County, Pennsylvania, to
      explore the effects of various school closure strategies on mitigating influenza
      epidemics of different reproductive rates (R0). RESULTS: Entire school system
      closures were not more effective than individual school closures. Any type of
      school closure may need to be maintained throughout most of the epidemic (ie, at
      least 8 weeks) to have any significant effect on the overall serologic attack
      rate. In fact, relatively short school closures (ie, 2 weeks or less) may
      actually slightly increase the overall attack rate by returning susceptible
      students back into schools in the middle of the epidemic. Varying the illness
      threshold at which school closures are triggered did not seem to have substantial
      impact on the effectiveness of school closures, suggesting that short delays in
      closing schools should not cause concern. CONCLUSIONS: School closures alone may
      not be able to quell an epidemic but, when maintained for at least 8 weeks, could
      delay the epidemic peak for up to a week, providing additional time to implement
      a second more effective intervention such as vaccination.

PMID- 20035237
TI  - Outcome of surgical resection for pathologic N0 and Nx non-small cell lung
      cancer.
AB  - PURPOSE: Metastasis to lymph nodes (LNs) connotes poor prognosis in non-small
      cell lung cancer (NSCLC). Sufficient LNs must be examined to accurately determine
      LN negativity. Patients with no LNs examined (pNx) have an indeterminate stage,
      may have undetected disease and erroneous assignment to a low-risk group. To
      evaluate this possibility, we compared the survival of patients with node
      negative disease and at least one LN examined (pN0) to those with pNx. METHODS:
      Retrospective analysis of all resections for NSCLC from January 1, 2004 to
      December 31, 2007 at hospitals in the Memphis Metropolitan Area. RESULTS: Of 746
      resections, 90 (12.1%) were Nx; 506 (67.8%) N0. Demographic and histologic
      characteristics were similar. A total of 54.4% Nx patients had sublobar
      resection, compared with 5.5% N0 (p < 0.0001). In the N0 cohort, the median
      (range) number of LNs was 5 (1-45); N1 LNs, 3 (0-38); N2 LNs, 1 (0-29); 35.4% had
      no mediastinal LNs examined; 9.1% had only mediastinal LNs. Eighty- five percent
      of N0 patients had less than 10 LNs. The 3-year survival estimate for the T1NxM0
      versus T1N0M0 patients was 70% versus 79% (p = 0.17); for T2NxM0 versus T2N0M0,
      it was 25% versus 65% (p < 0.01). CONCLUSIONS: A high percentage of patients
      undergoing surgical resection for NSCLC have no LNs examined, most of these
      patients have had sublobar resection. Majority with node-negative disease have
      fewer than 10 LNs, a large proportion have no mediastinal LNs, raising the
      possibility of understaging. Patients with pT2Nx do significantly worse than
      those with pT2N0.

PMID- 20035239
TI  - IL1B rs1143634 polymorphism, cigarette smoking, alcohol use, and lung cancer risk
      in a Japanese population.
AB  - BACKGROUND: Interleukin 1B (IL1B) is involved in pulmonary inflammation induced
      by environmental or occupational toxins. Chronic inflammation has been implicated
      in the development of lung cancer. METHODS: We evaluated the role of IL1B
      (rs1143634, 3954C>T) in a case-control study comprised of 462 lung cancer cases
      and 379 controls in a Japanese population. Logistic regression was used to assess
      the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS AND
      DISCUSSION: Individuals with a history of smoking and at least one T allele
      (adjusted OR = 5.45, 95% CI = 2.75-4.42, p < 0.01) presented a higher risk of
      lung cancer than those with the CC genotype (adjusted OR = 2.86, 95% CI = 2.02
      4.05, p < 0.01) as compared with never smokers with the CC genotype (reference).
      The adjusted attributable proportion because of interaction between the IL1B
      rs1143634 genotypes and smoking was estimated to be 0.45 (95% CI = 0.08-0.83, p =
      0.02), indicating that 45% of the excess risk for lung cancer in ever smokers
      with at least one T allele was due to additive interaction. Subjects with
      excessive alcohol intake and at least one T allele had a significantly higher
      risk (OR = 2.48, 95% CI =1.36-4.54, p < 0.01) than drinkers with appropriate
      intake and the CC genotype. There was no interaction between the polymorphism and
      alcohol intake. CONCLUSIONS: Our findings indicate the possible association of
      the T allele carriers of the IL1B rs1143634 polymorphism with higher risk of lung
      cancer especially among smokers. Additional studies are warranted to confirm the
      IL1B rs1143634-smoking interaction suggested in this study.

PMID- 20035238
TI  - Genetic and proteomic features associated with survival after treatment with
      erlotinib in first-line therapy of non-small cell lung cancer in Eastern
      Cooperative Oncology Group 3503.
AB  - INTRODUCTION: Serum proteomics and mutations in the epidermal growth factor
      receptor (EGFR) and KRAS have been associated with benefit after therapy with
      EGFR-targeted therapies in non-small cell lung cancer, but all three have not
      been evaluated in any one study. HYPOTHESIS: Pretreatment serum proteomics
      predicts survival in Western advanced non-small cell lung cancer patients with
      wild-type EGFR and independent of KRAS mutation status. METHODS: We analyzed
      available biospecimens from Eastern Cooperative Oncology Group 3503, a single-arm
      phase II study of erlotinib in first-line advanced lung cancer, for proteomics
      signatures in the previously described serum matrix-assisted laser desorption
      ionization proteomic classifier (VeriStrat) as well as for KRAS and EGFR
      mutations. RESULTS: Out of 137 enrolled patients, analyzable biologic samples
      were available on 102. Nine of 41 (22%) demonstrated KRAS mutations and 3 of 41
      (7%) harbored EGFR mutations. VeriStrat classification identified 64 of 88 (73%)
      as predicted to have "good" and 24 of 88 (27%) predicted to have "poor" outcomes.
      A statistically significant correlation of VeriStrat status (p < 0.001) was found
      with survival. EGFR mutations, but not KRAS mutations, also correlated with
      survival. CONCLUSIONS: The previously defined matrix-assisted laser desorption
      ionization predictor remains a potent and highly clinically significant predictor
      of survival after first-line treatment with erlotinib in patients with wild-type
      EGFR and independent of mutations in KRAS.

PMID- 20035240
TI  - Histone deacetylase inhibitors in malignant pleural mesothelioma: preclinical
      rationale and clinical trials.
AB  - Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer of the
      mesothelium with only a limited range of treatment options that are largely
      ineffective in improving survival. Recent efforts have turned toward the analysis
      of specific, dysregulated biologic pathways for insight into new treatment
      targets. Epigenetic regulation of tumor suppressor genes through chromatin
      condensation and decondensation has emerged as an important mechanism that leads
      to tumorogenesis. A family of histone acetyltransferases and deacetylases
      regulates this balance, with the latter facilitating chromatin condensation, thus
      preventing gene transcription, resulting in the loss of heterozygosity of tumor
      suppressors. Inhibition of this process, coupled with a similar inhibition of
      nonhistone protein deacetylation, ultimately leads to the promotion of apoptosis,
      cell cycle arrest, and inhibition of angiogenesis. An increasing amount of
      preclinical data highlighting the effectiveness of histone deacetylase inhibition
      in MPM cell lines and mouse xenograft models has led to a number of early phase
      clinical trials in patients with MPM. The results of these efforts have led to a
      multicenter, randomized, placebo-controlled phase III study of the histone
      deacetylase inhibitor vorinostat in patients with advanced MPM, offering hope for
      a new and effective therapy in patients with this disease.

PMID- 20035241
TI  - Comparison of two drug combinations for dilating dark irides.
AB  - PURPOSE: Two combinations of dilation drops [1% tropicamide and 2.5%
      phenylephrine (TP) vs. 1% tropicamide and 1% cyclopentolate (TC)] were compared
      to determine time course and magnitude of dilation for patients with dark irides.
      METHODS: Forty-five subjects, aged 4 to 32 years, with dark irides were enrolled.
      Photographs were taken before dilation and at 5, 10, 15, 20, 40, and 60 min after
      instillation of drops. Subjects received TP in one eye and TC in the fellow eye,
      with eyes randomized to the combination received. An examiner masked to drug
      combination and time used digital analysis to calculate pupil diameter for each
      photograph. TP and TC were compared to determine the time to reach both 6- and 7
      mm pupil diameter and the percentage of subjects reaching these diameters.
      RESULTS: Ninety-eight percent of pupils reached 6 mm with either combination;
      however, 80% reached 7 mm with TP and only 58% with TC (p = 0.0062, McNemars
      exact test). Time at which 50% of pupils reached 6 mm was not significantly
      different between drug combinations (TP 11 min vs. TC 12 min, Kaplan-Meier
      survival analysis). However, time at which 50% reached 7 mm was statistically and
      clinically significant (TP 32 min vs. TC 52 min, p = 0.0325). For subjects < or
      =10 years vs. >10 years, there was no significant difference in time at which 50%
      reached a 6- or 7-mm pupil with TP or TC; however, in every case, the younger
      group took longer. CONCLUSIONS: A 6-mm pupil dilation may be obtained with either
      TP or TC; however, more subjects achieved a 7-mm pupil with TP than TC and had a
      faster time course to attain that size.

PMID- 20035242
TI  - Green laser pointers for visual astronomy: how much power is enough?
AB  - PURPOSE: Green laser pointers with output powers in the tens to hundreds of
      milliwatt (mW) range, clearly exceeding the limiting 5 mW of American National
      Standards Institute class 3a (International Electrotechnical Commission class
      3R), are now easily available in the global market. They are increasingly being
      used in public sky observations and other nighttime outreach activities by
      educators and science communicators in countries where their use is not well
      regulated, despite the fact that such high power levels may represent a potential
      threat to visual health. The purpose of this study was to determine the output
      power reasonably required to perform satisfactorily this kind of activities.
      METHODS: Twenty-three observers were asked to vary continuously the output power
      of a green laser source (wavelength 532 nm) until clearly seeing the laser beam
      propagating skyward through the atmosphere in a heavily light-polluted urban
      setting. Measurements were conducted with observers of a wide range of ages (9 to
      56 years), refractions (spherical equivalents -8.50 to +1.50 diopters), and
      previous expertise in using lasers as pointing devices outdoors (from no
      experience to professional astronomers). Two measurement runs were made in
      different nights under different meteorological conditions. RESULTS: The output
      power chosen by observers in the first run (11 observers) averaged to 1.84 mW (+/
      0.68 mW, 1 SD). The second run (17 observers) averaged to 2.91 mW (+/-1.54 mW).
      The global average was 2.38 mW (+/-1.30 mW). Only one observer scored 5.6 mW,
      just above the class 3a limit. The power chosen by the remaining 22 observers
      ranged from 1.37 to 3.53 mW. CONCLUSIONS: Green laser pointers with output powers
      below 5 mW (laser classes American National Standards Institute 3a or
      International Electrotechnical Commission 3R) appear to be sufficient for use in
      educational nighttime outdoors activities, providing enough bright beams at
      reasonable safety levels.

PMID- 20035243
TI  - Differences in the perception of monocular and binocular gaze.
AB  - PURPOSE: The judged direction of side gaze from a straight head is known to be
      biased from its true direction. This study reports the specific biases in the
      perceived direction of gaze from right, left, or both eyes when targets are in
      the plane of the observer or in a plane in front of the observer. Theories are
      discussed about the ocular cues that are used to determine the perceived
      direction of gaze. METHODS: Two sets of 16 observers judged the direction of gaze
      from each of two models whose LCD-imaged heads gazed toward points that were
      either on the plane of the observers' faces or on a plane that was midway between
      the models and observers. RESULTS: For both distant and near targets, straight
      monocular gaze from the right and left eyes appeared to be mildly exotropic, as
      expected from the positive angle kappa of the models, but straight binocular gaze
      appeared orthotropic. However, when binocular gaze was toward the side, the
      perceived direction of gaze differed significantly between the two eyes, and for
      this condition, the perception of binocular gaze followed that of the abducting
      eye. CONCLUSION: When the perceived directions of monocular gaze from the two
      eyes do not agree, the perceived direction of binocular gaze resolves this
      conflict by matching that of the abducting eye.

PMID- 20035244
TI  - Compliance with contact lens replacement in Canada and the United States.
AB  - PURPOSE: To assess eye care practitioners (ECPs) recommendations for replacement
      frequency (RF) of silicone hydrogel (SH) and daily disposable (DD) lenses in
      Canada and the U.S. and to compare noncompliance (NC) with manufacturer
      recommended RF by the ECP and patient, and the reasons given for NC. METHODS:
      Invitations to participate were sent by e-mail to ECPs in Canada and the U.S.
      Twenty patient surveys were sent to 420 ECPs, and 2232 eligible surveys were
      received from 216 ECPs (26% Canada, 74% U.S.). Questions related to patient
      demographics, lens type, wearing patterns, ECP instructions for RF, and actual
      patient RF. ECPs provided lens information and their recommendation for RF after
      the surveys were completed and sealed in envelopes. Responses were anonymous.
      RESULTS: DD accounted for 18% (Canada) vs. 16% (U.S.) of wearers (p > 0.05); 35%
      (Canada) vs. 45% (U.S.) wore 2-week replacement SH (2WR; p = 0.011); and 47%
      (Canada) vs. 39% (U.S.) wore 1-month replacement SH (1MR) lenses (p = 0.025).
      Thirty-four percent (Canada) vs. 18% (U.S.) of ECPs recommended longer RFs than
      the manufacturer recommended RF for 2WR lens wearers (p < 0.001); 6% (Canada) vs.
      4% (U.S.) for DD wearers; and 2% (Canada) vs. 1% (U.S.) for 1MR lens wearers. NC
      rates for actual RFs reported by patients were not different between countries (p
      > 0.05) and were lowest for DD (13% Canada, 12% U.S.), followed by 1MR (33%
      Canada, 28% U.S.). The highest NC rates were with 2WR (50% Canada, 52% U.S.). The
      most frequent reason for NC with 2WR and 1MR was "forgetting which day to replace
      lenses" (54% Canada, 53% U.S.) and in DD wearers "to save money" (56% Canada, 29%
      U.S., p < 0.001). CONCLUSIONS: 1MR lenses are more frequently prescribed in
      Canada. ECPs in Canada were NC with 2WR lenses more frequently than U.S. ECPs,
      but patient NC rates were the same in both countries for all lens types. ECP and
      patient NC rates were highest for 2WR lens wearers.

PMID- 20035245
TI  - Oseltamivir for treatment of influenza in infants less than one year: a
      retrospective analysis.
AB  - BACKGROUND: Influenza causes proportionately more hospitalizations and deaths in
      infants in their first year of life than in older children. Oseltamivir is an
      effective treatment for childhood influenza, but few data are available in
      infants <1 year. METHODS: Medical records of infants <1 year admitted to hospital
      during the influenza seasons 2003-2007 were retrospectively analyzed to evaluate
      clinical presentation, and safety and outcome with oseltamivir therapy. Eligible
      infants were those with fever (>38 degrees C), influenza-like symptoms of sudden
      onset, positive rapid influenza test and parental consent, who received
      oseltamivir within 48 hours of the start of symptoms. Infants vaccinated against
      influenza or receiving immunosuppressants were excluded. RESULTS: In 157
      evaluable infants (mean age 6.3 [SD 3.2] months; 86 boys), the most common
      presenting symptoms other than fever were rhinitis, pharyngitis, cough, feeding
      difficulties, and otitis media. During treatment, additional symptoms were
      observed in 78 (50%) infants; most of these were gastrointestinal (vomiting and
      diarrhea) and of mild intensity. Fever resolved in 128 (82%) infants within 36
      hours of starting oseltamivir (136 [87%] within 48 hours). Complications were
      recorded in 84 patients (54%), the most serious of which were meningitis in 1
      infant (1%), pneumonia in 9 (6%), and otitis media in 2 (1%). Twenty infants
      received antibiotics for secondary infections (10 [6%] before admission).
      CONCLUSIONS: The clinical presentation of influenza and outcome of oseltamivir
      treatment in infants <1 year was similar to that previously reported in older
      children, but mild gastrointestinal symptoms were common.

PMID- 20035246
TI  - Prophylactic intratracheal polymyxin B/surfactant prevents bacterial growth in
      neonatal Escherichia coli pneumonia of rabbits.
AB  - In neonatal pneumonia, the surface activity of pulmonary surfactant is impaired
      and microorganisms may invade by passing the air-liquid interface. Previously, we
      have shown that addition of the antimicrobial peptide polymyxin B (PxB) to
      modified porcine surfactant (pSF) improves resistance to surfactant inactivation
      in vitro while antimicrobial activity of PxB is maintained. In this study, we
      investigated pSF/PxB in vivo. Neonatal near-term rabbits were treated with
      intratracheal pSF and/or PxB. Rabbits treated with only saline served as
      controls. Animals were ventilated with standardized tidal volumes and received
      ~10(7) Escherichia coli intratracheally. Plethysmographic pressure-volume curves
      were recorded every 30 min. After 240 min, animals were killed, the right lung
      and left kidney were excised, and bacterial growth was determined. The left lung
      was used for histologic analysis. Intratracheal administration of PxB +/- pSF
      significantly reduced the growth of E. coli compared with control animals or
      animals receiving only pSF. This was accompanied by reduction of severe
      inflammatory tissue destruction and significantly reduced bacterial translocation
      to the left kidney. Animals receiving pSF + PxB had no difference in lung
      compliance compared with the pSF- or PxB-treated group. Mixtures of PxB and
      pulmonary surfactant show antimicrobial effects in neonatal rabbits and prevent
      systemic spreading of E. coli.

PMID- 20035247
TI  - Impact of breast milk on intelligence quotient, brain size, and white matter
      development.
AB  - Although observational findings linking breast milk to higher scores on cognitive
      tests may be confounded by factors associated with mothers' choice to breastfeed,
      it has been suggested that one or more constituents of breast milk facilitate
      cognitive development, particularly in preterms. Because cognitive scores are
      related to head size, we hypothesized that breast milk mediates cognitive effects
      by affecting brain growth. We used detailed data from a randomized feeding trial
      to calculate percentage of expressed maternal breast milk (%EBM) in the infant
      diet of 50 adolescents. MRI scans were obtained (mean age=15 y 9 mo), allowing
      volumes of total brain (TBV) and white and gray matter (WMV, GMV) to be
      calculated. In the total group, %EBM correlated significantly with verbal
      intelligence quotient (VIQ); in boys, with all IQ scores, TBV and WMV. VIQ was,
      in turn, correlated with WMV and, in boys only, additionally with TBV. No
      significant relationships were seen in girls or with gray matter. These data
      support the hypothesis that breast milk promotes brain development, particularly
      white matter growth. The selective effect in males accords with animal and human
      evidence regarding gender effects of early diet. Our data have important
      neurobiological and public health implications and identify areas for future
      mechanistic study.

PMID- 20035248
TI  - Molecular microbiological characterization of preterm neonates at risk of
      bronchopulmonary dysplasia.
AB  - The role of infection in bronchopulmonary dysplasia (BPD) is unknown. We present
      an observational study of 55 premature infants born weighing less than 1.3 kg
      within two level III neonatal intensive care units. Endotracheal aspirates (ETA)
      and nasogastric aspirates (NGA) were studied with denaturing gradient gel
      electrophoresis (DGGE) profiling to elucidate the total bacterial community, and
      species-specific PCR was used to detect the presence of Mycoplasma hominis,
      Ureaplasma urealyticum, and Ureaplasma parvum. DGGE identified bacterial species
      in 59% of NGA and ETA samples combined. A diverse range of species were
      identified including several implicated in preterm labor. Species-specific PCR
      identified M. hominis in 25% of NGA and 11% of ETA samples. Among the 48 infants
      surviving up to 36 wk-postconceptual age, ordinal logistic regression showed the
      odds ratio for BPD or death where Ureaplasma was present/absent as 4.80 (95% CI
      1.15-20.13). After adjusting for number of days ventilated, this was reduced to
      2.04 (0.41-10.25). These data demonstrate how the combined use of DGGE and
      species-specific PCR identifies a high exposure in utero and around the time of
      birth to bacteria that might be causally related to preterm delivery and
      subsequent lung injury.

PMID- 20035249
TI  - Development of mechanisms associated with neurogenic-mediated skin inflammation
      during the growth of rats.
AB  - Neurogenic-mediated inflammation may be associated with several inflammatory skin
      diseases including atopic dermatitis. However, age-dependent differences in
      neurogenic-mediated skin responses are not fully understood. We compared skin
      plasma leakage in rats aged 2 and 8 wk, which was induced by topical capsaicin,
      topical formalin, and intracutaneous substance P, whose effects are mediated via
      tachykinin NK1 receptors. Evans blue dye extravasation served as an index of the
      increase in skin vascular permeability. Capsaicin, formalin, and substance P
      caused a skin response in a dose-dependent manner in both age groups. However,
      the skin response was much greater in adults than in pups. In addition, the
      localization of sensory C-fibers and tachykinin NK1 receptors in the skin was
      investigated by immunofluorescent staining with antisubstance P and
      antitachykinin NK1 receptor antibodies, respectively. Substance P-immunoreactive
      nerves were detected throughout the dermis and tachykinin NK1 receptors were
      mainly detected in blood vessel walls in the dermis in both age groups. However,
      they were more sparsely distributed in pups. In conclusion, the weak neurogenic
      mediated skin inflammation in pups is probably because of immature neural
      mechanisms associated with skin inflammation such as reduced innervation of
      sensory C-fibers and low expression of tachykinin NK1 receptors.

PMID- 20035250
TI  - Long-term improvement of deceased donor renal allograft survival since 1996: a
      single transplant center study.
AB  - BACKGROUND: The rate of acute rejection (AR) has decreased significantly, but
      whether this is associated with improvement in long-term graft survival is
      controversial. METHODS: We analyzed 1445 consecutive adult deceased donor kidney
      transplant recipients from 1985 to 2005, over two periods (1985-1995 vs. 1996
      2005) to compare long-term graft survival. RESULTS: The second period was
      associated with older donors and recipients and a reduction in AR. A significant
      increase of 10.1 months at 11 years was seen in death-censored graft survival in
      1996 to 2005. For this posttransplant time, graft half-life was 10.8 years in
      1985 to 1995, while at this point in the second period 62% of recipients had a
      functioning graft. The yearly increase in serum creatinine was less pronounced in
      the latter period (0.05 mg/dL vs. 0.02 mg/dL, P<0.01). No difference was found in
      patient survival. Cox analysis showed that donor age (HR 1.02, P<0.001), AR (HR
      1.72, P<0.001), panel-reactive antibody at transplantation (HR 1.01, P<0.001),
      and serum creatinine at 1 year (HR 2.01, P<0.001) had a negative impact on graft
      outcome. By contrast, the use of mycophenolate mofetil was associated with a 24%
      reduction in graft loss rate (HR 0.76, P<0.05). CONCLUSION: Long-term graft
      survival and renal function have improved in renal transplant recipients since
      1996.

PMID- 20035251
TI  - "Functional" or "psychosomatic" symptoms, e.g. a flu-like malaise, aches and pain
      and fatigue, are major features of major and in particular of melancholic
      depression.
AB  - BACKGROUND: Major depression is characterized by multifarious symptoms and
      symptoms clusters, such as the melancholic and anxiety symptom clusters. There is
      a strong comorbidity and a biological similarity between major depression and
      myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). OBJECTIVE: The aim
      of the present study was to examine "psychosomatic" symptoms reminiscent of
      ME/CFS in major depression. METHODS: Toward this end, we examined the 12-item
      Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale and the Hamilton
      Depression Rating Scale (HDRS) in 103 major depressed patients by means of
      multivariate pattern recognition methods. results: Our findings support the
      existence of two factors, i.e. a fatigue and somatic (F&S) factor, i.e aches and
      pain, muscular tension, fatigue, concentration difficulties, failing memory,
      irritability, irritable bowel, headache, and a subjective experience of
      infection; and a depression factor, i.e. sadness, irritability, sleep disorders,
      autonomic symptoms, and a subjective experience of infection. Cluster analysis
      performed on the 12 FF items found two different clusters, which were separated
      by highly significant differences in the F&S items, the most significant being a
      subjective experience of infection, aches and pain, muscular tension, fatigue,
      concentration difficulties and failing memory. Multivariate analyses showed that
      the differences between both clusters were quantitatively, and not qualitatively,
      and reflected the severity of the F&S dimension. There was a strong association
      between the F&S symptoms and melancholia and chronic depression. Treatment
      resistant depression was characterized by higher scores on the depression factor
      score. There was a strong correlation between the HDRS score and the FF items,
      fatigue, a subjective experience of infection, and sadness. Our findings show
      that F&S symptoms are a major feature of depression and largely predict severity
      of illness, and chronic and melancholic depression. CONCLUSIONS: It is concluded
      that the diagnostic criteria of depression and melancholia and rating scales to
      measure severity of illness should be modified to include the F&S symptom
      profile.

PMID- 20035252
TI  - Tianeptine treating narcolepsy. Case report.
AB  - Modafinil and Methylphenidate are proven to be effective in treating Narcolepsy,
      but also antidepressants that enhance synaptic levels of noradrenaline and
      serotonin have been reported as having some therapeutic efficacy. The patient
      reported in this article received Tianeptine 37.5 mg for two consecutive months.
      One week after start of treatment improvement of both sleepiness and cataplexy
      could be noticed. He showed an improvement of the Epworth Sleepiness Scale Score
      from 22 up to 16.

PMID- 20035253
TI  - Salivary alpha-amylase levels and rejection of unfair offers in the ultimatum
      game.
AB  - OBJECTIVES: This study aimed to examine the role of emotions in rejection of
      unfair offers in an ultimatum game, which is of interest in neuroeconomics of
      fairness. METHODS: Thirty-seven participants played a one-shot ultimatum game as
      responders and decided whether to accept or reject the unfair offers by the
      proposers. Salivary alpha-amylase (sAA) was assessed before and after the
      ultimatum game. RESULTS: Forty-four percent of the participants rejected the
      unfair offers. While sAA levels of the participants who rejected the unfair
      offers increased between pre- and post-experiment, sAA levels of the participants
      who accepted the unfair offers remain unchanged. CONCLUSIONS: Emotional stress
      response was observed when participants rejected the unfair offers. Our results
      indicated that rejection of the unfair offers is a reflection of emotional
      arousal associated with adrenergic activations.

PMID- 20035254
TI  - Psychological dissociation in obsessive-compulsive disorder is associated with
      anxiety level but not with severity of obsessive-compulsive symptoms.
AB  - OBJECTIVE: According to recent findings, clinical symptoms in patients with
      obsessive-compulsive disorder (OCD) seem be related with dissociation. The aim of
      the present study was to evaluate the relationship of psychological dissociation
      and clinical characteristics in OCD. METHODS: The study sample comprised of 49
      patients with OCD (55.1% females) and 45 healthy controls (66.7% females). All
      participants were assessed with the Yale-Brown Obsessive-Compulsive Scale, the
      Beck Depression Inventory-II, and the Beck Anxiety Inventory. Dissociation was
      quantified by the Dissociative Experiences Scale (DES). RESULTS: Psychological
      dissociation assessed with the DES was associated with the severity of anxiety
      symptoms (beta=0.49, t=3.89, df=47, p<0.001), but not with the level of OCD
      symptoms. Patients had higher level of dissociation than healthy controls.
      CONCLUSION: Our results suggest that the level of psychological dissociation is
      associated with the severity of anxiety symptoms rather than with OCD symptoms.
      Further investigation of association between dissociative and anxiety states is
      needed.

PMID- 20035255
TI  - Predicting the therapeutic response to cognitive behavioural therapy in patients
      with pharmacoresistant obsessive-compulsive disorder.
AB  - OBJECTIVE: The aim of our study was to establish the efficacy of CBT on the
      sample of non-selected medication-resistant patients with OCD and to search for
      predictors of therapeutic response in such a group. METHODS: The treatment was
      carried out under usual conditions at the department for anxiety disorders.
      Systematic CBT steps were tailored to the needs of each patient. Pharmacology
      treatment remained grossly unchanged during the trial period. We used the
      following outcome measures in the study: Yale-Brown Obsessive Compulsive Scale,
      subjective version (S-Y-BOCS), the Clinical Global Impression - Severity of
      Illness scale (CGI-S), Beck Depression Inventory (BDI), Beck Anxiety Inventory
      (BAI), Somatoform Dissociation Questionnaire (SDQ-20) and Dissociative Experience
      Scale (DES). The primary outcome measure was a decrease by 35% in Y-BOCS rating.
      Remission was defined as a 12 point score or lower in Y-BOCS and 1 or 2 points in
      CGI-S. RESULTS: 47 patients completed the study (19 male and 28 female). One
      female patient refused to participate. All patients completed at least 5 weeks of
      intensive CBT programme and showed significant improvement on Y-BOCS, CGI-S, and
      BDI scales. At the end of the treatment 40.4% of the patients achieved clinical
      remission according to the CGI-S scale. The main characteristics present at the
      beginning of the trial increasing probability of achieving improvement or
      remission during the treatment were a Y-BOCS score lower than 22, good insight,
      higher resistance to symptoms, low level of dissociation, and aggressive
      obsessions. CONCLUSION: As negative predictors we identified higher scores in Y
      BOCS, poorer insight, low resistance to symptoms, high level of dissociation,
      obsessions focused on control/symmetry and obsessive slowness/ambivalence as
      associated with poor improvement.

PMID- 20035256
TI  - MR imaging - an unreliable and potentially misleading diagnostic modality in
      patients with intracerebral calcium depositions. Case report.
AB  - BACKGROUND: Since magnetic resonance imaging (MRI) is a method of choice for
      establishing the correct diagnosis in a great majority of neurologic disorders,
      especially in detection the causes of seizures and both acute and slowly
      progressive neurologic disturbances, computerized tomography is becoming more
      frequently excluded from obligate spectrum of diagnostic protocol. METHODS: MRI
      was performed on 1.5 T MR scanner in two patients, in one suffering from
      pseudohypoparathyroidism, and in another with Fahr disease, while CT was
      initially excluded from the diagnostic protocol. In third patient, 11-year-old
      boy with hypercalcemia, both CT and MRI were indicated because of seizure attack.
      RESULTS: Completely normal appearing brain parenchyma was seen on T2W images in a
      patient with clinical diagnosis of pseudohypoparathyroidism while extensive
      intracerebral calcifications were noted after additionally performed computerized
      tomography of the brain. In another patient with Fahr disease and neurologic
      symptoms, extensive calcifications were evident on CT, while MR examination had
      revealed bilateral symmetric lesions of prolonged T2W signal in the basal
      ganglia, supratentorial white matter and cerebellum, most compatible
      toxic/metabolic demyelination. In the third patient, a boy with hypercalcemia,
      marked left parietal cortical calcification was noted on CT, while MRI, including
      T2 gradient-echo sequence was inconclusive. CONCLUSIONS: MRI, without CT, can be
      not only confusing, but even misleading diagnostic modality for detection of not
      only subtle, but also extensive cerebral calcifications. The benefit of gradient
      echo T2 sequence, that is usually included in MR protocol when intracranial
      calcifications are suspected, is also rather limited.

PMID- 20035257
TI  - Macular thickness and volume after uncomplicated phacoemulsification surgery
      evaluated by optical coherence tomography. A one-year follow-up.
AB  - OBJECTIVE: To evaluate changes in the macular thickness and volume using optical
      coherence tomography in patients after phacoemulsification and intracapsular
      implantation of a foldable intraocular lens. MATERIALS AND METHODS: The study
      included 82 patients (37 males and 45 females) after phacoemulsification and
      intracapsular implantaion of the same type of a foldable intraocular lens,
      without any other eye disease. Phacoemulsification was performed with an INFINITI
      machine. In all patients, macular thickness and volume were measured with an
      optical coherence tomograph (Stratus OCT) using the Fast Macular Thickness Map.
      The OCT evaluation was performed on days 1, 7, 30 and 90 postoperatively. In 58
      patients (71%), it was additionally performed at 12 months after surgery and in
      52 patients (63%) the macular parameters in the healthy and operated eyes were
      compared. RESULTS: A statistically significant increase in the minimal retinal
      thickness was observed on days 30 (p<0.0005) and 90 (p<0.005) postoperatively
      compared to post-operative day 1. A statistically significant increase in the
      foveal volume was seen on days 30 (p<0.00005) and 90 (p<0.0005). A statistically
      significant increase in the volume of the entire macula was found on days 7, 30
      and 90 (p<0.00005). CONCLUSION: Uncomplicated cataract phacoemulsification is
      followed by increases in the central retinal thickness, foveal volume and volume
      of the entire macula on days 30 and 90 and at 12 months postoperatively. Further
      observation of patients is required to confirm whether the macular parameters
      will return to their values on day 1 postoperatively and if so, when this will
      occur.

PMID- 20035258
TI  - Luzindole but not 4-phenyl-2- propionamidotetralin (4P-PDOT) diminishes the
      inhibitory effect of melatonin on murine Colon 38 cancer growth in vitro.
AB  - OBJECTIVE: Our earlier studies have shown that MLT exerts the inhibitory effect
      on murine cancer via membrane and nuclear receptors. We have found that the
      antagonist of MT1 receptors does not diminish the antiproliferative effect of MLT
      on Colon 38 cells, and the contribution of MT2 receptors has been suggested to be
      responsible. Therefore, in the present study we have examined the influence of
      the 4-phenyl-2-propionamidotetralin (4P-PDOT), which is a selective antagonist of
      MT2 membrane receptor, and luzindole - an antagonist of both membrane receptors,
      on an oncostatic action of MLT. MATERIALS AND METHODS: The murine cancer cell
      line Colon 38 was used in the experiments. In 48 hrs cell culture the effects of
      MLT, 4P-PDOT and luzindole administered alone and MLT applied jointly with either
      4P-PDOT or luzindole were examined. The growth of cancer cells was assessed using
      the modified colorimetric Mosmann method. RESULTS: Melatonin at both examined
      concentrations (10-7, 10-9 M) significantly decreased the viability of cancer
      cells. The selective antagonist of MT2 membrane receptor, namely 4P-PDOT and
      luzindole applied separately did not have an effect on the growth of Colon 38
      cells. The addition of 4P-PDOT to MLT did not change the inhibitory effect of
      MLT, whereas luzindole given together with MLT diminished, but failed to block
      totally, the oncostatic properties of MLT. CONCLUSIONS: The obtained data and our
      previous studies conducted on Colon 38 cancer indicate that membrane melatonin
      receptors are not indispensable to the oncostatic action of melatonin and thus
      other pathways such as nuclear signaling and receptor-independent mechanism may
      be also involved.

PMID- 20035259
TI  - Impact of repeated methamphetamine pretreatment on intravenous self
      administration of the drug in males and estrogenized or non- estrogenized
      ovariectomized female rats.
AB  - OBJECTIVE: The female animals were already recorded to respond differently to
      methamphetamine (MET) abuse than males. This gender dissimilarity may be caused
      by the influence of estral cycles and different susceptibility to behavioural
      sensitization. METHODS: Influences of gender and pre-exposure to MET were studied
      in the rat model of MET intravenous self-administration (IVSA). The fixed ratio
      (FR) paradigm was employed in male rats (M) and estrogenized (F-ESTR) and non
      estrogenized ovariectomized female rats (F-OVX) either pre-exposed or not-exposed
      to MET pretreatment. RESULTS: In rats that were not pre-exposed to MET, F-ESTR
      self-administered more MET infusions than each of the other groups, but F-OVX
      self-administered less than each of the other groups; the same trend was apparent
      in the MET pretreated groups. MET pre-exposure decreased subsequent MET IVSA in
      all groups except F-OVX. CONCLUSION: Thus, pre-exposure to MET and the loss of
      inherent estrogen in females notably decreased the intake of MET by rats,
      suggesting that abuse liability was reduced. Estrogen's effects on MET self
      administration here correspond with accumulating evidence of stronger behavioural
      responses of females to drugs of abuse.

PMID- 20035261
TI  - Effects of maternal lipids on the fetal growth in gestational diabetes.
AB  - OBJECTIVE: The aim of this study was to determine whether there is an association
      between ultrasound fetal biometry and lipids and glucose profiles at the
      beginning of gestational diabetes (GDM) treatment. METHODS: In 98 women with GDM
      plasma glucose and lipid profile were measured between 27-32 weeks' of gestation.
      The association between the biochemical parameters and the measurements and
      percentiles of the biparietal diameter (BPD), femur length (FL) and abdominal
      circumference (AC), estimated fetal weight (EFW) and the actual birthweight (BW)
      were analyzed. RESULTS: There was no significant association between fetal and
      neonatal biometry measurements and maternal glucose concentrations. Highly
      significant positive correlation was found between triglicerydes and fetal
      biometry at the beginning of GDM treatment: AC, BPD, FL and EFW (p=0.007,
      p=0.018, p=0.018, p=0.013, respectively), as well as between total cholesterol
      and bi-parietal diameter (p=0.04). Associations between maternal plasma lipids
      and birthweight or birthweight percentile were not evident. CONCLUSIONS: These
      data suggest that maternal lipids and carbohydrates metabolic disturbance are an
      important determinant for fetal growth in pregnancy before gestational diabetes
      is diagnosed.

PMID- 20035260
TI  - Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major
      depression and myalgic encephalomyelitis / chronic fatigue syndrome.
AB  - BACKGROUND: There is now evidence that major depression and myalgic
      encephalomyelitis / chronic fatigue syndrome (ME/CFS) are accompanied by
      partially overlapping pathophysiological mechanisms, i.e. activation of various
      inflammatory and oxidative & nitrosative (IO&NS) pathways. OBJECTIVE: The aim of
      the present study was to examine the urinary excretion of 8-hydroxy
      deoxyguanosine (8-OhdG), a marker of oxidative damage to DNA, in depression;
      ME/CFS; and depression and ME/CFS. METHODS: Toward this end, morning urine was
      sampled for the assays of 8-OHdG and creatinine, in 44 patients with ME/CFS; 25
      with major depression; 23 with depression and ME/CFS; and 17 normal controls.
      Severity of fatigue and somatic symptoms was measured by means of the
      Fibromyalgia and CFS Rating (FF) scale. RESULTS: We found that 49.0% of the
      variance in the urinary excretion of 8-OHdG was predicted by the regression on
      creatinine. Consequently, the urinary 8-OHdG excretion should be expressed as the
      residualized 8-OHdG values after partialling out the effects of creatinine and
      not by computing the 8-OHdG / creatinine ratio. We found that the residualized
      urinary excretion of 8-OHdG (adjusted for creatinine) was significantly higher in
      patients with depression and ME/CFS than in normal controls and all other
      patients. In the patient group, there were significant correlations between the
      urinary 8-OHdG and the total score on the FF scale and sadness and flu-like
      malaise. CONCLUSIONS: The findings show increased oxidatively generated DNA
      damage in patients with major depression and ME/CFS and, therefore, further
      extent the role played by IO&NS pathways in the pathophysiology of both
      disorders. Since oxidatively damage to DNA is a risk factor for atherosclerosis
      and neurodegeneration, our results also explain previous findings on increased
      cardiovascular morbidity in depression and ME/CFS, and neurodegenerative
      processes in depression.

PMID- 20035262
TI  - Effect of the new pyridoindole antioxidant SMe1EC2 on functional deficits and
      oedema formation in rat hippocampus exposed to ischaemia in vitro.
AB  - OBJECTIVES: The idea of neuroprotective therapy for ischaemic stroke is based on
      results from studies on experimental animal models of brain ischaemia
      demonstrating efficacy of many natural and synthetic agents. Contrary to positive
      conclusions with antioxidants from animal models, clinical experience failed to
      find neuroprotectants so efficient in human stroke, infarction, brain trauma,
      tissue preservation, etc. Thus new highly effective neuroprotective agents need
      to be discovered. METHODS: Effects of 10-day oral treatment with the new
      pyridoindole derivative, code SMe1EC2, was analysed in the model of ischaemia in
      vitro measured five days after oral treatment, with focus on neuronal function
      recovery. The responses were determined by extracellular recording from rat
      hippocampal slices. Further, effect of SMe1EC2, applied into the incubation
      medium before and during ischaemia in vitro, was studied on the oedema extent in
      neurons of the CA1 area. RESULTS: Ten-day oral treatment of rats with SMe1EC2 at
      the doses 50 or 250 mg/kg resulted in improved resistance of hippocampal neurons
      to 6.5-min hypoxia/hypoglycaemia in vitro measured during reoxygenation, compared
      to untreated rats. Application of the drug tested into the incubation medium 30
      min before and during 6-min hypoxia/hypoglycaemia resulted in reduction of oedema
      formation in the CA1 area compared to untreated slices exposed to ischaemia in
      vitro. CONCLUSION: The current study confirmed the neuroprotective effect of the
      pyridoindole antioxidant SMe1EC2 on the level of recovery of neuronal function as
      well as on affection of morphological changes expressed by reduced oedema extent
      in the rat hippocampus under ischemic conditions in vitro.

PMID- 20035263
TI  - Dopamine beta hydroxylase (DBH) plasma activity in childhood mental disorders.
AB  - BACKGROUND: Developmental study of dopaminergic and noradrenergic systems in
      child psychiatric disorders are rare. DBH activity is one of noradrenergic
      biochemical marker that is correlate in psychiatry to clinical and genetic data.
      OBJECTIVES: The main aim of the present study was to measure DBH activity at the
      onset of acute schizophrenia and depressive disorder in children and adolescents
      without pharmacological treatment and to compare these values with DBH activity
      in healthy controls. The authors also investigated untreated ADHD children.
      METHODS: We examined 42 control healthy children, 15 children non-treated with
      acute schizophrenia, 15 non-treated children with acute depressive disorders and
      30 non-treated ADHD children, all in age 7-14. Plasma DBH level was provided by
      Nagatsu (1972; 1974). Depressed children were reexamined after clinical
      remission. RESULTS: DBH activity is statistically significantly decreased in non
      treated depressive disorder and ADHD in children and adolescents. DBH activity is
      normalised during antidepressant therapy in child depression. Child schizophrenia
      patients present with normal DBH activity. CONCLUSION: These results are similar
      to the results that have been observed in adult patients with schizophrenia and
      depression and in previous studies of DBH activity in children with ADHD. These
      results also indicate hypoactivity of the noradrenergic system in children with
      ADHD and depression.

PMID- 20035264
TI  - Daytime sleepiness and changes of sleep architecture in patients with epilepsy.
AB  - OBJECTIVE: The relationship between epilepsy and sleep has been known for many
      years. Yet is still not well understood because of it's reciprocal and intrinsic
      influences. Epileptic manifestations during sleep may lead to fragmentation of
      sleep stages. On the other hand insomnia or other sleep disorders may cause sleep
      deprivation and increase number of epileptic seizures in patients with epilepsy.
      The study is designed to compare daytime sleepiness and architecture of sleep in
      patients with epilepsy and control subjects. We tried to evaluate factors that
      have influence on sleep architecture of patients with epilepsy. METHODS: We
      evaluated the daytime sleepiness through a certain type of questionnaire called
      Epworth Scale of Sleepiness (ESS). The questionnaire was filled out by patients
      with epilepsy (83 patients) and a group of healthy controls (80 persons).
      Furthermore we evaluated the quatity of night sleep in both groups using
      polysomnograph (electroencephalography - EEG, electrooculography - EOG,
      electromyography - EMG). Sleep stages were scored according to Manual of
      Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human
      Subjects (Rechtschaffen, Kales, 9). Multiple sleep latency test (MSLT) was
      performed in the group of patients with epilepsy in order to objectivise daytime
      sleepiness. RESULTS: Measuring by Epworth scale of sleepiness we found out that
      the patients with epilepsy suffered from a significantly higher daytime
      sleepiness than the healthy controls. Patients with epilepsy also experienced
      significant changes in sleep architecture, the reduction of NREM S3, S4 and REM
      stages and the increase of NREM S2 stage. These changes were not related to used
      antiepileptic medication.

PMID- 20035265
TI  - Chlamydia trachomatis infection in women with lichen sclerosus vulvae and vulvar
      cancer.
AB  - OBJECTIVE: Chronic infections in the urogenital area often precede or coexist
      with vulvar cancer. A strong connection between some tumours and the-appearance
      of Chlamydia trachomatis infection has been observed, but there is little
      information concerning a connection of that infection with vulvar cancer and
      lichen sclerosus vulvae (LS). The aim of this study was the analysis of frequency
      of antigens appearance and antibodies of IgM and IgG Chlamydia trachomatis in
      patients with vulvar cancer and LS and we wanted to find the correlation between
      Chlamydia trachomatis infection and vulvar cancer and LS. METHODS: 80 women
      treated in the Clinic of Vulva Diseases at the Department and Clinical Ward of
      Gynaecology, Obstetrics and Oncological Gynaecology in Bytom, in the Silesian
      Medical University in Katowice were divided into two groups - 30 were treated for
      vulvar cancer and 50 were treated because of LS. We took bacterial smears vagina
      and cervical smears for presence of Chlamydia trachomatis antigens and peripheral
      blood to mark antibodies of IgM and IgG Chlamydia trachomastis. RESULTS:
      Chlamydia trachomatis antigen was found in 20% women with vulvar cancer and in
      12% women with LS (p>0.05). In 13,3% cases with vulvar cancer we observed IgM
      Chlamydia trachomatis antibodies. In the group with LS IgM antibodies appeared in
      16% women (p>0.05). In 50% patients with vulvar cancer in blood serum we observed
      IgG Chlamydia trachomatis antibodies, and in 16% women with LS (p<0.001).
      CONCLUSIONS: Previous Chlamydia trachomatis infection can lead to vulvar
      carcinogenesis.

PMID- 20035266
TI  - Assessment of chronic benign and cancer pain using blood plasma biomarkers.
AB  - OBJECTIVE: The objective was a systematic study of the biochemical markers which
      are descriptive for the dynamics of pain processes. MATERIALS AND METHODS: The
      patients who had not been systematically treated for pain prior to their
      participation in this study consisted of 20 non-oncological (mean age 56.5 years)
      and 20 oncological patients (mean age 64.8 years). Pain intensity, assessed using
      the visual analogue scale (VAS) on a scale from 0-10, and the following
      biochemical parameters were measured during the initial patient workups: blood
      serum total protein, glucose, total cholesterol, HDL cholesterol, LDL
      cholesterol, atherosclerotic indexes, triacylglyceroles, apolipoprotein A,
      apolipoprotein B, albumin, alpha1 globulin, alpha2 globulin, beta globulin and
      gamma globulin. Biochemical measurements were repeated as soon as VAS assessments
      fell below 5. Therapy in non-oncological patients involved administration of NSA
      and weak opioids; while oncological patients received NSA, medium strength and
      strong opioids, and antidepressants. RESULTS: Prior to therapy, concentration of
      albumin in serum, HDL cholesterol, and apolipoprotein A were lower, whereas CRP
      and alpha1 globulin were higher in oncological patients compared to non
      oncological patients. After therapy, levels of glucose and alpha1 globulin were
      significantly higher and levels of apolipoprotein A were lower in oncological
      patients compared to non-oncological patients. Irrespective of diagnosis,
      patients treated with antidepressants showed higher levels of gamma globulin
      compared to non treated patients. CONCLUSIONS: We can conclude that observed
      biochemical markers in patients with malignancies are more similar to the values
      of patients with chronic benign pain than to the values of patients with acute
      pain.

PMID- 20035267
TI  - Angioid streaks - clinical course and photodynamic therapy. Case report.
AB  - Angioid streaks develop as a result of damage to the Bruch's membrane. They may
      occur as idiopatic angioid streaks or in association with pseudoxanthoma
      elasticum, Paget's disease and the haemoglobinopathies. Other pathologies of the
      fundus of eye may coexist together with angioid streaks, such as drusen of an
      optic disc and granular-like retina in posterior pole known as "peau d'orange".
      Subretinal neovascularization as well as atrophy in macula are also observed in
      the cases of long-lasting pathologies. The diagnosis is based mainly on clinical
      manifestations. Photodynamic therapy in treatment patients with secondary
      choroidal neovasularisation appeared to be effective.

PMID- 20035268
TI  - Acute and chronic effects of antidepressants on the G-protein alpha subunit
      profiles in vitro and in vivo.
AB  - OBJECTIVES: Neurochemical studies on the etiopathogenesis of depression are also
      focusing on the transduction system beyond receptors. Trimeric G-proteins play a
      crucial role in the transmembrane signalling, signal amplification and
      intracellular processing. Abnormalities of G-protein levels are observed in
      subjects with depression, G-protein modulation is considered to play a role in
      the antidepressant mode of action. METHODS: We studied acute or chronic
      administration of antidepressants from different pharmacological groups. We used
      immunochemical estimation (ELISA) of the main types of G-protein alpha subunits
      from isolated membranes of C6 glioma cells and rat brain tissue. RESULTS:
      Significant elevation of G alpha q/11 subunits after chronic administration of
      sertraline and significant reduction of G alpha s subunit levels following both
      acute and chronic administrations of sertraline were found. In contrast, no
      significant effects on G alpha subunit levels following acute desipramine and
      moclobemide administration were observed in vitro. Chronic moclobemide effect in
      vivo is causing significant elevation of Galpha s and Galpha i1,2 subunit levels.
      CONCLUSIONS: Results show involvement of antidepressant drugs in the C6 glioma
      signal transduction cascades modulation in dependence on the antidepressant
      class. Significant influence in the cAMP system modulation is observed after
      administration both SSRI and MAOA inhibitors. Astrocytoma cells - C6 glioma cells
      also can offer a model system of the glia where modulation of cell signalization
      cascades can influence cell functioning and production of neurotrophic factor
      molecules relevant to the antidepressant treatment and depression
      etiopathogenesis.

PMID- 20035269
TI  - Action of melatonin on bone marrow depression induced by cyclophosphamide in
      acute toxicity phase.
AB  - BACKGROUND: In the course of the last few years, various studies have researched
      the relations linking melatonin (MLT) with hematopoiesis and the immune
      hematopoietic system. Nevertheless, to date there are numerous issues still
      opened and many questions are yet unanswered. Much emphasis has been recently
      placed on the reducing role of MLT, which has been demonstrated by many studies
      to mitigate the genotoxic damage inflicted by various alkylating agents. Although
      in vitro MLT has shown to be effective in limiting the cytological alterations
      provoked by chemotherapeutic drugs, some clinical studies seem to point to a
      somewhat lower effectiveness in countering chemotherapy-induced leukopenia and
      anemia. OBJECTIVE: The aim of this study was to evaluate the activity exerted by
      pharmacological doses of MLT in limiting leukopenia, anemia and other
      hemocytometric modifications in animals facing acute toxicity caused by the
      treatment with cyclophosphamide (CP). Moreover, we have compared the activity of
      MLT with well-known alpha-tocopherol/ascorbic acid antioxidant system. RESULTS:
      Our results indicate that overall MLT exerts a remarkable countering activity
      towards leukopenia and anemia in the early phase of administration of CP.
      CONCLUSIONS: Our findings suggest possible active involvement of MLT in
      hematopoiesis and erythrocyte- and leukocyte turnover. This paper summarizes the
      essential aspects of the available literature, researching the possible relations
      between MLT and immune-hematopoietic system.

PMID- 20035270
TI  - Abnormalities of tau-protein and beta-amyloid in brain ventricle cerebrospinal
      fluid.
AB  - OBJECTIVE: Determination of various biomarkers, such as beta-amyloid, tau
      protein, phosphorylated tau-protein in CSF and their sensitivity and specificity
      in neurodegenerative brain processes, in particular Alzheimer Dementia (AD), has
      been recently investigated to monitor their abnormalities in the CSF at early
      stages of diseases before the clinical manifestation. DESIGN AND SETTING: In the
      pilot group of our patients (10 men / 5 women) who underwent a drainage
      neurosurgical procedure for diagnosis of hydrocephalus, CSF was obtained from the
      brain ventricles and the influence of a different compartment of the CSF on the
      level of biomarkers, tau-protein and beta-amyloid, was investigated. RESULTS: The
      mean tau-protein level for all 15 patients was 812.0 pg/ml, with median value
      363.7 pg/ml; while mean beta-amyloid level for all 15 patients was 526.7 pg/ml,
      with median value 239.5 pg/ml, respectively. The abnormal tau-protein and beta
      amyloid levels were found in the subgroup of patients in whom hydrocephalus was
      caused by a severe pathological process, such as brain tumor. The beta-amyloid
      values were significantly lower also in comparison with our previously published
      results in patients with AD in the CSF obtained by lumbar puncture in the spinal
      canal. CONCLUSIONS: CSF in the brain ventricles is theoretically more stable and
      the values in this CSF probably provide more reliable informations for clinical
      diagnostic procedure than those for the CSF obtained by lumbar puncture in the
      spinal canal.

PMID- 20035271
TI  - A new link between steroid resistance, glucocorticoid receptor and nuclear factor
      kappa B p65 in idiopathic nephrotic syndrome.
AB  - OBJECTIVES: The aim of our study was to investigate levels of glucocorticoid
      receptor (GRalpha), nuclear factor kappa B (NFkappaB) p65/p50 and inhibitor of
      NFkappaB alpha (IkappaBalpha) in the peripheral mononuclear blood cells (PMBC) of
      children with idiopathic nephrotic syndrome (INS). METHODS: The expression of
      GRalpha, NFkappaBp65/p50 and IkappaBalpha was determined in 59 patients (age
      10.2+/-5.1) and 25 healthy controls (CO) (age 13.1+/-3.4) using Western blot
      analysis. Patients were labeled according to their clinical sensitivity to
      glucocorticoids (GCs) as responders (RE), partial responders (PR), and non
      responders (NR). RESULTS: Significantly higher expressions of GRalpha were
      observed in RE than in PR, NR (p<0.01) and even CO (p<0.05). Similarly,
      expression of NFkappaBp65 was higher in RE in comparison to PR, NR and CO
      (p<0.05). These differences were more emphasized in the relapse: levels of
      GRalpha were significantly lower in PR than in RE and CO (p<0.01). Significant
      differences were also observed in expression of NFkappaB: RE showed significantly
      higher expression of NFkappaBp65 in comparison to PR, NR and even CO (p<0.01).
      CONCLUSIONS: Lower levels of both GRalpha and NFkappaBp65 are associated with
      poor or no response to GCs and the difference is more pronounced in patients
      experiencing relapse of INS.

PMID- 20035272
TI  - Freezing and thawing human embryonic stem cells.
AB  - Since James Thomson et al developed a technique in 1998 to isolate and grow hES
      in culture, freezing cells for later use and thawing and expanding cells from a
      frozen stock have become important procedures performed in routine hES cell
      culture. Since hES cells are very sensitive to the stresses of freezing and
      thawing, special care must taken. Here we demonstrate the proper technique for
      rapidly thawing hES cells from liquid nitrogen stocks, plating them on mouse
      embryonic feeder cells, and slowly freezing them for long-term storage.

PMID- 20035273
TI  - Evaluation of left ventricular synchronicity in hypertensive patients with
      overweight or obesity.
AB  - The left ventricular synchronicity in hypertensive patients with overweight or
      obesity has not been well elucidated. This study was designed to evaluate the
      left ventricular synchronicity in these patients. Tissue Doppler imaging was
      performed in 126 hypertensive patients and 25 control subjects. The hypertensive
      patients were divided into three groups according to BMI: normal weight group
      (BMI <25 kg/m(2), n = 32, H-NW group), overweight group (BMI 25-29.9 kg/m(2), n =
      64, H-OW group), and obese group (BMI >or=30 kg/m(2), n = 30, H-OB group). Left
      ventricular systolic and diastolic synchronicity were determined by measuring the
      maximal differences in time to peak myocardial systolic contraction (T(s)-diff)
      and early diastolic relaxation (T(e)-diff) between any two of the left
      ventricular segments and the standard deviation of time to peak myocardial
      systolic contraction (T(s)-SD) and early diastolic relaxation (T(e)-SD) of all 12
      segments. Compared with the control group, the indexes of synchronicity including
      T(s)-diff, T(s)-SD, T(e)-diff, and T(e)-SD were significantly prolonged in the
      hypertensive patients. Furthermore, although the indexes of blood pressure had no
      difference among the hypertensive groups, the impaired systolic and diastolic
      synchronicity including T(s)-diff, T(s)-SD, and T(e)-SD was obviously aggravated
      with the increasing BMI. Stepwise multivariate analysis revealed BMI as an
      independent predictor of T(s)-SD and T(e)-SD. Therefore, the impairment of left
      ventricular synchronicity was aggravated with increasing BMI in hypertensive
      patients. Overweight and obesity may be important factors to impact the left
      ventricular synchronicity.

PMID- 20035274
TI  - Reducing portion size reduces food intake and plate waste.
AB  - As portion size (PS) increases, so does food intake. The effect of decreasing PS
      on food intake in a nonlaboratory setting is unknown. This 5-week study sought to
      determine whether decreasing PS resulted in decreased intake of the same food,
      and if so, at what point further PS reductions might lack benefit. It also
      assessed effects of PS reduction on food production and waste in a university all
      you-can-eat dining facility (DF). Subjects were primarily freshmen who regularly
      ate lunch at the DF, and self-selected French fries (FF) presented in individual
      paper bags, portioned originally at 88 g, and decreased approximately 15 g/week
      for 3 weeks. Diners were covertly observed choosing one or more bags. Total FF
      production and plate waste (PW) were determined daily. Decreasing PS resulted in
      significant decreases in consumption per diner (P < 0.05) and PW (P < 0.05), and
      nonsignificant decreases in total FF consumption and production. PS was
      positively correlated with consumption per diner (r = 0.897, P = 0.001) and PW (r
      = 0.852, P = 0.001), but inversely correlated with number of diners choosing
      >or=2 bags (r = -0.809, P = 0.003). Total FF production was positively correlated
      with PW (r = 0.728, P = 0.011). This study shows that reducing PS of a particular
      item in an all-you-can-eat environment results in reduced intake of that food for
      most individuals, and that reducing PS reduces PW and food production.

PMID- 20035275
TI  - Energy expenditure and oxygen consumption as novel biomarkers of obesity-induced
      cardiac disease in rats.
AB  - The purpose of the present study was to determine calorimetric parameters to
      predict obesity adverse effects on oxidative stress and cardiac energy
      metabolism. Male Wistar 24 rats were divided into three groups (n = 8): given
      standard chow and water (C), receiving standard chow and 30% sucrose in its
      drinking water (S), and given sucrose-rich diet and water (SRD). After 45 days,
      both S and SRD rats had obesity, serum oxidative stress, and dyslipidemic
      profile, but the body weight gain and feed efficiency (FE) were higher in SRD
      than in S, whereas the obesity-related oxidative stress, myocardial
      triacylglycerol accumulation, and enhanced cardiac lactate dehydrogenase (LDH)
      activity were higher in S than in SRD rats. Myocardial beta-hydroxyacyl coenzyme
      A-dehydrogenase was lower in SRD and in S than in C, whereas glycogen was only
      depleted in S rats. Myocardial pyruvate dehydrogenase (PDH) was lowest in S rats
      indicating depressed glucose oxidation. There was higher myocardial LDH/citrate
      synthase (CS) ratio and lower adenosine triphosphate (ATP)-synthetase indicating
      delayed aerobic metabolism in S rats than in the others. Cardiac ATP-synthetase
      was positively correlated with energy expenditure, namely resting metabolic rate
      (RMR), and with oxygen consumption per body weight (VO(2)/body weight).
      Myocardial lipid hydroperoxide (LH)/ total antioxidant substances (TAS) ratio and
      triacylglycerol accumulation were negatively correlated with RMR and with
      VO(2)/body weight. In conclusion, the present study brought new insights into
      obesity because the study demonstrated for the first time that reduced energy
      expenditure and oxygen consumption may provide novel risk factors of obesity
      induced reduced energy generation for myocardial contractile function. The
      results serve to highlight the role of calorimetric changes as novel biomarkers
      of risk to obesity-induced cardiac effects.

PMID- 20035276
TI  - Anthropometric measures and risk of epithelial ovarian cancer: results from the
      nurses' health study.
AB  - Epidemiologic evaluations of the relationship between anthropometry and ovarian
      cancer risk have not been conclusive. Using data collected from two large
      cohorts, the Nurses' Health Study (NHS) and NHSII, we prospectively evaluated the
      association between waist and hip circumference, the waist-to-hip ratio (WHR),
      and BMI with risk of epithelial ovarian cancer. Women completed biennial
      questionnaires assessing ovarian cancer risk factors beginning in 1976 (NHS) and
      1989 (NHSII). For the WHR and BMI analyses, 333 and 862 confirmed cases were
      identified, respectively, through 1 June 2006 (NHS) and 1 June 2005 (NHSII). WHR
      and waist circumference were not associated with risk (P-trend = 0.63 and 0.65,
      respectively). There was evidence for a decreased risk with increasing hip
      circumference among postmenopausal women (P-trend = 0.03), but a suggestive
      positive association among premenopausal women (P-trend = 0.04) (P-interaction =
      0.01). The hazard ratios (HRs) comparing the highest vs. lowest quintile of hip
      circumference among pre- and postmenopausal women were 1.54 (95% confidence
      interval (CI) = 0.45-5.23) and 0.66 (95%CI = 0.37-1.16), respectively. BMI was
      not clearly associated with risk in pre- or postmenopausal women. Results from
      this large prospective study suggest that hip circumference could be a possible
      risk factor for premenopausal ovarian cancer, but may reduce risk of
      postmenopausal ovarian cancer. The differential effect of hip circumference based
      on menopausal status requires further confirmation.

PMID- 20035278
TI  - Longitudinal trends in obesity in the United States from adolescence to the third
      decade of life.
AB  - No longitudinal analyses using national data have evaluated the increase in
      obesity from adolescence into early adulthood. We examined obesity incidence,
      persistence, and reversal in a nationally representative cohort of US teens
      followed into their early 30s, using measured height and weight data, in
      individuals enrolled in wave II (1996; 12-21 years), wave III (2001; 17-26
      years), and wave IV (2008 early release data; 24-32 years) of the National
      Longitudinal Study of Adolescent Health (N = 8,675). Obesity was defined as a BMI
      >or=95th percentile of the 2000 Centers for Disease Control/National Center for
      Health Statistics growth charts or >or=30 kg/m(2) for individuals <20 years and
      >or=30 kg/m(2) in individuals >or=20 years. In 1996, 13.3% of adolescents were
      obese. By 2008, obesity prevalence increased to 36.1%, and was highest among non
      Hispanic black females (54.8%). Ninety percent of the obese adolescents remained
      obese in 2008. While annual obesity incidence did not decline in the total sample
      across the two study intervals (2.3% per year 1996-2001 vs. 2.2% per year 2001
      2008), rates among white females declined (2.7 to 1.9% per year) and were highest
      among non-Hispanic black and Hispanic females (3.8 and 2.7% per year, 1996-2001
      vs. 3.0 and 2.6% per year, 2002-2008, respectively). Obesity prevalence doubled
      from adolescence to the early 20s, and doubled again from the early to late 20s
      or early 30s, with strong tracking from adolescence into adulthood. This trend is
      likely to continue owing to high rates of pediatric obesity. Effective preventive
      and treatment efforts are critically needed.

PMID- 20035277
TI  - Respiration in adipocytes is inhibited by reactive oxygen species.
AB  - It is a desirable goal to stimulate fuel oxidation in adipocytes and shift the
      balance toward less fuel storage and more burning. To understand this regulatory
      process, respiration was measured in primary rat adipocytes, mitochondria, and
      fat-fed mice. Maximum O(2) consumption, in vitro, was determined with a chemical
      uncoupler of oxidative phosphorylation (carbonylcyanide p
      trifluoromethoxyphenylhydrazone (FCCP)). The adenosine triphosphate/adenosine
      diphosphate (ATP/ADP) ratio was measured by luminescence. Mitochondria were
      localized by confocal microscopy with MitoTracker Green and their membrane
      potential (Delta psi(M)) measured using tetramethylrhodamine ethyl ester
      perchlorate (TMRE). The effect of N-acetylcysteine (NAC) on respiration and body
      composition in vivo was assessed in mice. Addition of FCCP collapsed Delta psi(M)
      and decreased the ATP/ADP ratio. However, we demonstrated the same rate of
      adipocyte O(2) consumption in the absence or presence of fuels and FCCP.
      Respiration was only stimulated when reactive oxygen species (ROS) were scavenged
      by pyruvate or NAC: other fuels or fuel combinations had little effect.
      Importantly, the ROS scavenging role of pyruvate was not affected by rotenone, an
      inhibitor of mitochondrial complex I. In addition, mice that consumed NAC
      exhibited increased O(2) consumption and decreased body fat in vivo. These
      studies suggest for the first time that adipocyte O(2) consumption may be
      inhibited by ROS, because pyruvate and NAC stimulated respiration. ROS inhibition
      of O(2) consumption may explain the difficulty to identify effective strategies
      to increase fat burning in adipocytes. Stimulating fuel oxidation in adipocytes
      by decreasing ROS may provide a novel means to shift the balance from fuel
      storage to fuel burning.

PMID- 20035279
TI  - Effect of obesity on growth-related oncogene factor-alpha, thrombopoietin, and
      tissue inhibitor metalloproteinase-1 serum levels.
AB  - We have recently identified several adipokines as oversecreted by omental adipose
      tissue (AT) of obese subjects: two chemokines (growth-related oncogene factor
      alpha (GRO-alpha), macrophage inflammatory protein-1 beta (MIP-1 beta)), a tissue
      inhibitor of metalloproteinases-1 (TIMP-1), an interleukin-7 (IL-7) and a
      megakaryocytic growth-factor (thrombopoietin (TPO)). These adipokines are
      involved in insulin resistance and atherosclerosis. The objectives of this study
      were to determine whether the circulating levels of these adipokines were
      increased in obesity and to identify the responsible factors. A cross-sectional
      study including 32 lean (BMI (kg/m(2)) <25), 15 overweight (BMI: 25-29.9), 11
      obese (BMI: 30-39.9), and 17 severely obese (BMI >40) age-matched women was
      carried out. Serum adipokine levels, insulin sensitivity, and substrate oxidation
      were measured by ELISA, euglycemic-hyperinsulinemic clamp, and indirect
      calorimetry, respectively. Circulating levels of GRO-alpha, TPO, and TIMP-1 were
      higher in obese and/or severely obese women than in lean ones (+30, 55, and 20%,
      respectively). Serum levels of these adipokines positively correlated with
      insulinemia or glycemia, and negatively with insulin sensitivity. TIMP-1 also
      positively correlated with blood pressure, and TPO with triglyceride levels.
      Multiple regression analysis showed that fat mass per se was an independent
      determinant of GRO-alpha, TPO, and TIMP-1 levels, suggesting that hypertrophied
      adipocytes and recruited macrophages in expanded AT mainly contribute to this
      hyperadipokinemia. Insulinemia, glycemia and resistance of glucose oxidation to
      insulin were additional predictors for TPO. Circulating GRO-alpha, TPO, and TIMP
      1 levels are increased in obesity. This may be partially due to augmented
      adiposity per se and to hyperinsulinemia/insulin resistance. These high systemic
      levels may in turn worsen/promote insulin resistance and cardiovascular disease.

PMID- 20035280
TI  - Adolescent obesity and future college degree attainment.
AB  - The current impact of adolescent obesity on educational attainment is not clear.
      The objectives of our study were to determine whether adolescent obesity is
      associated with college degree attainment and how this association may have
      changed over time. We used data from a contemporary national cohort of over 4,000
      persons who were adolescents (aged 14-18) in 1997 to assess the relationship
      between adolescent obesity and education. To assess for changes in this
      relationship over time, we also analyzed an older, similarly structured cohort of
      over 3,000 persons who were adolescents (aged 16-18) in 1981. Our primary outcome
      was college degree completion. We found that in the older cohort (adolescents in
      1979), there were no differences in college degree attainment by adolescent
      weight status before and after adjustment. However, unadjusted analysis of the
      contemporary cohort (adolescents in 1997) demonstrated that those who were normal
      weight as adolescents had a higher prevalence of college degree attainment at
      follow-up compared to obese adolescents (24% vs. 10%). After adjustment for socio
      demographic variables (age, sex, race, height, parental income-to-poverty ratio,
      parental education, aptitude test scores), obese adolescents were less likely to
      have attained a college degree compared to normal weight peers (adjusted risk
      ratio 0.61 95% confidence interval 0.38-0.83). Expectations for a future college
      degree did not vary by weight status and did not explain this observation. In
      conclusion, adolescent obesity is associated with lower likelihood of college
      completion. This relationship was not observed in an older cohort of adolescents.

PMID- 20035281
TI  - Visfatin is a positive regulator of MCP-1 in human adipocytes in vitro and in
      mice in vivo.
AB  - Visfatin is a proinflammatory and potentially insulin-mimetic adipokine
      contributing to whole body glucose and lipid metabolism, as well as
      atherosclerosis. Monocyte chemoattractant protein (MCP)-1 is an adipocyte
      secreted protein which might play a crucial role in metabolic and vascular
      disease. MCP-1 expression and secretion after visfatin treatment were determined
      by quantitative real-time reverse transcription-PCR and enzyme-linked
      immunosorbent assay (ELISA) in fully differentiated human mesenchymal stem cell
      derived adipocytes (hMSC-Ads) in vitro. In addition, circulating levels of MCP-1
      and visfatin were quantified by ELISA in 60 patients (30 nondiabetic, 30
      diabetic) and MCP-1 serum levels in mice were determined after visfatin treatment
      in vivo. Interestingly, protein secretion and mRNA production of MCP-1 were
      induced significantly in hMSC-Ads after visfatin stimulation. Visfatin-induced
      MCP-1 secretion 1.9-fold after 8 h and 2.5-fold after 24 h relative to untreated
      cells (P < 0.05). MCP-1 mRNA synthesis was significantly stimulated by visfatin
      with maximal upregulation detectable at 250 ng/ml visfatin and after 4 h of
      treatment. Signaling studies suggested that p44/42 mitogen-activated protein
      (MAP) kinase is involved in visfatin-induced MCP-1 mRNA expression in hMSC-Ads.
      Detectability of visfatin in serum predicted circulating MCP-1 independent of age
      and gender in humans in vivo. MCP-1 serum levels were significantly increased
      more than twofold after visfatin treatment in mice in vivo. Taken together, our
      results demonstrate that visfatin upregulates MCP-1 supporting a possible role of
      MCP-1 in mediating the proinflammatory effects of visfatin.

PMID- 20035282
TI  - Glucose metabolism and diet predict changes in adiposity and fat distribution in
      weight-reduced women.
AB  - Among obesity-prone individuals, metabolic state may interact with diet in
      determining body composition. We tested the hypotheses that, among 103 weight
      reduced women over 1 year, (i) insulin sensitivity would be positively associated
      with change in %fat; (ii) this association would be modulated by dietary glycemic
      load (GL); and (iii) changes in fat distribution would be related to indexes of
      glucose metabolism. Insulin sensitivity, glucose effectiveness, fasting and
      postchallenge insulin and glucose, and glucose tolerance were assessed during
      intravenous glucose tolerance test (IVGTT). Changes in %fat and fat distribution
      were examined using dual-energy X-ray absorptiometry and computed tomography.
      Dietary GL was assessed on 67 women using food records. On average, women showed
      a +5.3 +/- 3.0% change in %fat over 1 year, with the magnitude of this change
      being greater in relatively insulin sensitive women (+6.0 +/- 0.4%, mean +/-
      s.e.m.) than in relatively insulin resistant women (+4.4 +/- 0.4 kg; P < 0.05).
      Women who were relatively insulin sensitive and who consumed a higher GL diet
      showed a +6.8 +/- 0.7% change in %fat, which was greater than those who were less
      insulin sensitive, regardless of diet (P < 0.05), but did not differ from women
      who were relatively insulin sensitive and who consumed a lower GL diet (P =
      0.105). Changes in intra-abdominal and deep subcutaneous abdominal fat were
      inversely associated with the postchallenge decline in serum glucose. In
      conclusion, greater insulin sensitivity may predispose to adiposity among weight
      reduced women, an effect that may be ameliorated by a lower GL diet. The
      potential association between indexes of glucose disposal and changes in fat
      distribution warrants further study.

PMID- 20035284
TI  - The lipid accumulation product and all-cause mortality in patients at high
      cardiovascular risk: a PreCIS database study.
AB  - The BMI is the most frequently used marker to evaluate obesity-associated risks.
      An alternative continuous index of lipid over accumulation, the lipid
      accumulation product (LAP), has been proposed, which is computed from waist
      circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC - 65) x TG
      (men) and (WC - 58) x TG (women). We evaluated LAP and BMI as predictors of
      mortality in a high-risk cohort. Study population included 5,924 new consecutive
      patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty
      eight percent of patients were discordant for their LAP and BMI quartiles.
      Patients whose LAP quartile was greater than BMI quartile had higher mortality
      compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4%
      at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes
      mellitus, blood pressure, low-density lipoprotein-cholesterol (LDL-C) and high
      density lipoprotein-cholesterol (HDL-C), (ln)LAP was independently associated
      with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with
      increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including
      traditional risk factors for atherosclerosis increased its predictive value (C
      statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not
      change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed
      that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP
      1.64, P < 0.001), but did not reach significance in the diabetic patients (HR =
      1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in
      nondiabetic patients at high risk for cardiovascular diseases. LAP may become a
      useful tool in clinical practice to stratify the risk of unfavorable outcome
      associated with obesity.

PMID- 20035283
TI  - Sociodemographic, perinatal, behavioral, and psychosocial predictors of weight
      retention at 3 and 12 months postpartum.
AB  - Postpartum weight retention plays an important role in the pathway leading to
      obesity among women of childbearing age. The objective of this study was to
      examine predictors of moderate (1-10 pounds) and high (>10 pounds) postpartum
      weight retention using data from a prospective pregnancy cohort that followed
      women into the postpartum period; n = 688 and 550 women at 3 and 12 months,
      respectively. Analysis included descriptive statistics and predictive modeling
      using log-binomial techniques. The average weight retained at 3 and 12 months
      postpartum in this population was 9.4 lb (s.d. = 11.4) and 5.7 lb (s.d. = 13.2),
      respectively. At 3 months postpartum, prepregnancy weight, gestational weight
      gain, and hours slept during the night were associated with moderate or high
      weight retention, whereas having an infant hospitalized after going home and
      scoring in the upper 75th percentile of the Eating Attitudes Test (EAT) were
      associated only with high weight retention. At 12 months postpartum, prepregnancy
      weight, gestational weight gain, and maternal education were associated with
      moderate weight retention; and gestational weight gain, maternal age, race,
      employment status, and having an infant hospitalized at birth were associated
      with high weight retention. The results of this study illustrate the importance
      of prepregnancy weight and gestational weight gain in predicting postpartum
      weight retention. Furthermore, given the lack of successful intervention studies
      that exist to date to help women lose weight in the postpartum period, the
      results of this study may help to inform future interventions that focus on such
      aspects as hours of sleep, dealing with stress associated with a hospitalized
      infant, and nonclinical eating disorder symptomatology.

PMID- 20035285
TI  - Inflexibility in intramuscular triglyceride fractional synthesis distinguishes
      prediabetes from obesity in humans.
AB  - Whether intramuscular triglyceride (IMTG) concentration or flux is more important
      in the progression to type 2 diabetes is controversial. Therefore, this study
      examined IMTG concentration, as well as its fractional synthesis rate (FSR), in
      obese people with normal glucose tolerance (NGT; n = 20) vs. obese people with
      prediabetes (PD; n = 19), at rest and during exercise. Insulin action and
      secretion were assessed using an intravenous glucose tolerance test. [U
      (13)C]palmitate was infused for 4 h before and throughout 1.5 h of treadmill
      walking at 50% VO(2(max)). IMTG concentration was measured by gas
      chromatograph/mass spectrometer, and FSR by gas chromatography-combustion isotope
      ratio mass spectrometer, from muscle biopsies taken immediately before and after
      exercise. Basal IMTG concentration was higher (43 +/- 5.7 vs. 27 +/- 3.9 mg/mg
      dry weight, P = 0.03) and FSR trended lower (0.23 +/- 0.04 vs. 0.32 +/- 0.05/h, P
      = 0.075), as did insulin action (S(i); 2.9 +/- 0.43 vs. 3.3 +/- 0.35 x 10(
      4)/mU/ml, P = 0.07), in PD vs. NGT. IMTG concentration did not change
      significantly during exercise, but was no longer different in PD vs. NGT (45 +/-
      7.7 vs. 37 +/- 5.8 mg/mg dry weight, P = 0.41). IMTG FSR suppressed during
      exercise in NGT (-81% to 0.06 +/- 0.13/h, P = 0.02), but not PD (+4% to 0.24 +/-
      0.13%/h, P = 0.95). Palmitate oxidation was similar during rest (P = 0.92) and
      exercise (P = 0.94) between groups, but its source appeared different with more
      coming from muscle at rest and plasma during exercise in NGT, whereas the
      converse was true in PD. Altogether, higher basal IMTG concentration that is
      metabolically inflexible distinguishes obese people with PD from those with NGT.

PMID- 20035286
TI  - Significance of des-gamma-carboxy prothrombin production in hepatocellular
      carcinoma.
AB  - Serum des-gamma-carboxy prothrombin (DCP) is commonly used to detect
      hepatocellular carcinoma (HCC). This review focuses on the clinical features of
      DCP-positive HCC and the molecular function of DCP in HCC. DCP-positive HCC
      demonstrates more aggressive clinicopathological features than DCP-negative HCC.
      Analysis of the biological effects of DCP revealed that DCP acts as a growth
      factor in both an autocrine and paracrine manner. DCP stimulates HCC cell
      proliferation through the Met-Janus kinase 1-signal transducer and activator of
      transcription 3 signaling pathway, whereas for vascular endothelial cells, it
      stimulates cell proliferation and migration through the kinase insert domain
      receptor-phospholipase C-gamma-mitogen-activated protein kinase signaling
      pathway.

PMID- 20035287
TI  - Amphiphysin I and regulation of synaptic vesicle endocytosis.
AB  - Amphiphysin I, known as a major dynamin-binding partner localized on the collars
      of nascent vesicles, plays a key role in clathrin-mediated endocytosis (CME) of
      synaptic vesicles. Amphiphysin I mediates the invagination and fission steps of
      synaptic vesicles by sensing or facilitating membrane curvature and stimulating
      the GTPase activity of dynamin. Amphiphysin I may form a homodimer by itself or a
      heterodimer with amphiphysin II in vivo. Both amphiphysin I and II function as
      multilinker proteins in the clathrin-coated complex. Under normal physiological
      conditions, the functions of amphiphysin I and some other endocytic proteins are
      known to be regulated by phosphorylation and dephosphorylation. During
      hyperexcited conditions, the most recent data showed that amphiphysin I is
      truncated by the ca2-dependent protease calpain. Overexpression of the truncated
      form of amphiphysin I inhibited transferrin uptake and synaptic vesicle
      endocytosis (SVE). This suggests that amphiphysin I may be an important regulator
      for SVE when massive amounts of Ca2 flow into presynaptic terminals, a phenomenon
      observed in neurodegenerative disorders such as ischemia/anoxia, epilepsy,
      stroke, trauma and Alzheimer's disease. This review describes current knowledge
      regarding the general properties and functions of amphiphysin I as well as the
      functional regulations such as phosphorylation and proteolysis in nerve
      terminals.

PMID- 20035288
TI  - Inverse correlation between adiponectin and the risk of metabolic syndrome in
      middle-aged Japanese male workers.
AB  - Despite a close association between adiponectin and both hypertension and type 2
      diabetes, the relationship between adiponectin and metabolic syndrome has not yet
      been well-investigated. To examine and evaluate the association between serum
      adiponectin levels and metabolic syndrome based on Japanese diagnostic criteria,
      we analyzed adiponectin and anthropometric parameters in 869 male employees aged
      40-59 who belonged to a health insurance society in Fukuoka Prefecture and who
      underwent annual health check-ups from August 2006 to July 2007. Two hundred and
      thirty-two of the 869 subjects (26.7%) were diagnosed with metabolic syndrome.
      The serum adiponectin levels were significantly higher in the non-metabolic
      syndrome group. In a multiple logistic regression analysis, the subjects in the
      top quartile of serum adiponectin (adjusted odds ratio:0.36;95% confidence
      interval:0.21-0.63) and the second (adjusted odds ratio:0.51;95% confidence
      interval:0.31-0.84) quartile had a significantly decreased risk for metabolic
      syndrome in comparison to the bottom quartile. The dose-response relationship
      between serum adiponectin levels and metabolic syndrome was significant (p for
      trend 0.0001) after adjusting for age, body mass index, smoking status, and
      drinking status. The current findings suggest that hypoadiponectinemia is
      inversely correlated with the risk of metabolic syndrome in middle-aged Japanese
      male workers.

PMID- 20035289
TI  - Longevity-associated NADH dehydrogenase subunit-2 237 Leu/Met polymorphism
      modulates the effects of daily alcohol drinking on yearly changes in serum total
      and LDL cholesterol in Japanese men.
AB  - Reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 2 237
      leucine/methionine (ND2-237 Leu/Met) polymorphism, is reportedly associated with
      longevity in the Japanese population. The ND2-237Met genotype may exert
      resistance to atherogenic diseases, such as myocardial infarction or
      cerebrovascular disorders. To investigate whether ND2-237 Leu/Met polymorphism is
      associated with yearly changes in serum lipid levels, we conducted a longitudinal
      study of 107 healthy Japanese male subjects. Analysis of covariance revealed that
      the interaction between the ND2-237 Leu/Met genotypes and habitual drinking was
      significantly associated with yearly changes in serum total cholesterol (TC) and
      low-density lipoprotein cholesterol (LDLC) levels (p=0.036 and p=0.006,
      respectively). In multiple regression analysis, daily drinking was significantly
      and positively associated with yearly changes in serum LDLC levels in men with
      ND2-237Met (p=0.026). After adjusting for covariates, yearly changes in serum
      LDLC levels were significantly lower in non-daily drinkers with ND2-237Met than
      in those with ND2-237Leu (p=0.047). These results suggest that ND2-237Met has a
      beneficial impact on yearly changes in serum LDLC in non-daily drinkers but not
      in daily drinkers.

PMID- 20035291
TI  - Inflammatory cytokine-induced expression of vasohibin-1 by rheumatoid synovial
      fibroblasts.
AB  - Angiogenesis is an essential event in the development of synovial inflammation in
      rheumatoid arthritis (RA). The aim of the current study was to investigate the
      expression of vasohibin-1, a novel endothelium-derived vascular endothelial
      growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to
      test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA
      synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery
      from patients with osteoarthritis (OA) and RA, and subjected to
      immunohistochemistry to investigate the expression and distribution of vasohibin
      1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs
      were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR
      after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic
      conditions. The immunohistochemical results showed that vasohibin-1 was expressed
      in synovial lining cells, endothelial cells, and synovial fibroblasts. In
      synovial tissue, there was a significant correlation between the expression of
      vasohibin-1 and histological inflammation score (p=0.002, r=0.842). In vitro,
      stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under
      normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA
      expression under a hypoxic condition. These results suggest that vasohibin-1 was
      expressed in RA synovial tissue and might be regulated by inflammatory cytokines.

PMID- 20035290
TI  - Effects of sulfur amino acids on tyrosyl or serine/threonine phosphorylation and
      translocation of cytosolic compounds to cell membrane in stimulus-treated human
      neutrophils.
AB  - We investigated the effects of various sulfur amino acids on the phosphorylation
      of proteins and the translocation of cytosolic compounds to cell membrane in
      stimulus-treated human neutrophils using specific monoclonal antibodies. D,L
      homocysteine and D,L-homocysteine-thiolactone enhanced fMLP-induced tyrosyl
      phosphorylation of proteins and the translocation of p47phox, p67phox, and rac to
      the cell membrane in a concentration-dependent manner. L-cystathionine, NAc-L
      cysteine and carboxymethylcysteine suppressed the tyrosyl phophorylation and
      translocation of cytosolic compounds to the cell membrane. L-cystathionine, L
      cysteine and NAc-L-cysteine suppressed PMA-induced serine/threonine
      phosphorylation and the translocation of cytosolic compounds to the cell
      membrane. L-cysteine, NAc-L-cysteine and D,L-homocysteine enhanced AA-induced
      serine/threonine phosphorylation and the translocation of cytosolic compounds to
      the cell membrane, but L-cystathionine had opposite effects. These results
      indicated that the effects of sulfur amino acids on tyrosyl or serine/threonine
      phosphorylation and the translocation of p47phox, p67phox, and rac to the cell
      membrane in the stimulus-treated human neutrophils were in parallel with those of
      the stimulus-induced superoxide generation reported in previous paper. L
      cysteine, D,L-homocysteine and L-cystathionine weakly inhibited lipid
      peroxidation, but the other sulfur amino acids tested had no effect.

PMID- 20035292
TI  - Estimation of carrying angle based on CT images in preoperative surgical planning
      for cubitus deformities.
AB  - Conventionally, the carrying angle of the elbow is measured using simple two
      dimensional radiography or goniometry, which has questionable reliability. This
      study proposes a novel method for estimating carrying angles using computed
      tomography that can enhance the reliability of the angle measurement. Data of CT
      scans from 25 elbow joints were processed to build segmented three-dimensional
      models. The cross-sectional centerlines of the ulna and the humerus were traced
      from the 3D models, and the angle between 2 vectors formed from the centerlines
      of the humerus and the ulna was defined as the "three-dimensional carrying
      angle." These angles were compared with those measured by simple radiograph. Two
      cases of angular deformity were underwent surgery based on this preoperative
      surgical planning, and the postoperative 3D carrying angles were evaluated using
      the proposed method. The mean value of the calculated three-dimensional carrying
      angle was 20.7 degrees +/-3.61, while it was 16.3 degrees +/-3.21 based on simple
      radiography without statistical difference. Based on the 3D carrying angle
      estimations, 2 surgical cases of cubitus deformities were planned by comparison
      with the normal contra-lateral elbow. Postoperative angle estimations confirmed
      that the corrected angles were nearly identical to the planned angles for both
      cases. The results of this study showed that the carrying angle can be accurately
      estimated using three-dimensional CT and that the proposed method is useful in
      evaluating deformities of the elbow with high reliability.

PMID- 20035293
TI  - Breast cancer with cartilaginous and/or osseous metaplasia diagnosed by lymph
      nodal metastasis: a case report.
AB  - Breast cancer with cartilaginous and/or osseous metaplasia is a type of
      metaplastic carcinomas and is a rare disease. We report the case of a 49 year-old
      female who underwent right mastectomy for a large breast tumor. Histological
      examinations revealed a mixed tumor with both stromal and epithelial elements;the
      stroma showed poor differentiated spindle-shape and multiform cells with a
      massive osseous matrix, and atypical epithelial cells, which mainly existed on
      the surface of the cysts, showed nucleic atypia. The tumor was diagnosed as a
      malignant phyllodes tumor with osteosarcomatous differentiation;it was not
      identified as a metaplastic carcinoma because of the lack of proof of a cancerous
      component. Two years after a mastectomy, swelling of the axillary lymph nodes was
      found and a biopsy was performed. Histological findings for the lymph node
      indicated a metastasis of the invasive ductal carcinoma. The primary tumor was re
      examined and was considered to be the origin of the lymph nodal metastasis. Lymph
      nodal metastasis of cancer proved that the primary tumor had cancerous potential,
      and the pathological diagnosis was altered to a breast cancer with cartilaginous
      and/or osseous metaplasia.

PMID- 20035294
TI  - Computer navigation-assisted spinal fusion with segmental pedicle screw
      instrumentation for scoliosis with Rett syndrome: a case report.
AB  - Scoliosis is a common clinical manifestation of Rett syndrome, a
      neurodevelopmental disorder that almost exclusively affects females. The spinal
      curve in patients with Rett syndrome is typically a long C curve of a
      neuromuscular type. As the onset of the scoliosis is very early and shows rapid
      progression, early surgical intervention has been recommended to prevent a life
      threatening collapsing spine syndrome. However, there are high perioperative
      risks in Rett syndrome patients who undergo spinal surgery, such as neurological
      compromise and respiratory dysfunction due to rigid spinal curve. We herein
      report the surgical result of treating severe rapid progressive thoracic
      scoliosis in a 16-year-old girl with Rett syndrome. Posterior segmental pedicle
      screw fixation was performed from T1 to L3 using a computer-assisted technique.
      Post-operative radiography demonstrated a good correction of the curve in both
      the sagittal and coronal alignment. There were no postoperative complications
      such as neurological compromise. The patient had maintained satisfactory spinal
      balance as of the 3-year follow-up examination.

PMID- 20035295
TI  - Malignant amelanotic melanoma of the pleura without primary skin lesion:an
      autopsy case report.
AB  - Melanoma metastasizing to the lungs is common, but primary pulmonary or pleural
      melanoma is extremely rare. We present an autopsy case of malignant melanoma of
      the pleura without primary skin lesion in a 49-year-old man. A mass found in the
      right chest was diagnosed as spindle cell sarcoma by antemortem fine-needle
      aspiration cytology. At autopsy, a yellow-white tumor located primarily in the
      right visceral pleura (diagnosed as an amelanotic melanoma) was found to have
      invaded into the right lung, right parietal pleura, and right diaphragm, and to
      have metastasized into the left lung and visceral pleura, thyroid, and left
      adrenal gland. No primary site was found. The tumor cells were positive for S100
      and focally positive for HMB-45, but negative for other markers. Immuno
      histochemical examination for S100 and HMB-45 would thus appear to be useful for
      the diagnosis of an amelanotic melanoma.

PMID- 20035296
TI  - Standard optical coaxial double fiber diameter and refractive index measurement,
      accuracy, and precision using light scattering at normal incidence.
AB  - A plane-polarized laser wave with a wavelength of 441.6 nm illuminates a cladding
      optical fiber with a diameter of about 18 to 38 mum at normal incidence. A
      measured angular distribution of the intensity of the scattered wave corresponds
      well with the differential cross section of a rigorous theoretical calculation of
      a coaxial double cylinder over a wide range of scattering angle. The diameter and
      refractive index of the cladding and core of the illuminated part of a fiber have
      been determined accurately for each uncertainty.

PMID- 20035297
TI  - Analyzing halftone dot blurring by extended spectral prediction models.
AB  - Spectral prediction models for halftone prints generally assume homogeneously
      thick and sharply edged ink dots, i.e., bilevel halftones. In real prints, the
      ink thickness often decreases at the boundaries of the ink dots, thereby forming
      continuous-level halftones. The present study aims at verifying to what extent
      the classical Clapper-Yule and Yule-Nielsen models are able to predict the
      reflectance of single-ink continuous-level halftone prints. First we model the
      reflectance of continuous-level halftones by developing variable thickness
      extensions of both the Clapper-Yule and the Yule-Nielsen spectral prediction
      models. We consider continuous halftones whose thickness profiles are obtained by
      Gaussian filtering of the bilevel halftone image. Then we predict the reflectance
      spectra defined by the continuous-level models by fitting the bilevel models'
      effective ink surface coverages. Since dot blurring tends to increase the
      absorption of light by the ink, the effective ink surface coverage is larger than
      the nominal one, i.e., dot blurring induces its own contribution to dot gain. Dot
      blurring can also be accurately modeled by an increased n-value of the classical
      Yule-Nielsen model.

PMID- 20035298
TI  - Nondiffracting vortex-beams in a birefringent chiral crystal.
AB  - A vector-wave analysis of nondiffracting beams propagating along a birefringent
      chiral crystal for the case of tensor character of both the optical activity and
      linear birefringence is presented. We have written characteristic equations and
      found propagation constants and amplitude parameters of the eigenmodes. The
      characteristic curves have anomalous zones described by an isotropic point or a
      gap-point, provided that the elements of an optical activity tensor obey the
      requirement g(11)g(33)<0, |g(33)|>|g(11)|. In the anomalous zone, a
      nondiffracting beam can propagate through a purely chiral crystal as if through
      an isotropic medium. We have shown that the field of eigenmodes is nonuniformly
      polarized in the beam cross section, while the field with the initially uniform
      polarization distribution experiences periodic transformations. We have revealed
      that even a purely chiral crystal without linear birefringence can generate
      optical vortices in an initially vortex-free Bessel beam.

PMID- 20035299
TI  - Fast linear canonical transforms.
AB  - The linear canonical transform provides a mathematical model of paraxial
      propagation though quadratic phase systems. We review the literature on numerical
      approximation of this transform, including discretization, sampling, and fast
      algorithms, and identify key results. We then propose a frequency-division fast
      linear canonical transform algorithm comparable to the Sande-Tukey fast Fourier
      transform. Results calculated with an implementation of this algorithm are
      presented and compared with the corresponding analytic functions.

PMID- 20035300
TI  - White balance by tunable spectral responsivities.
AB  - The development of color pixels in modern digital imaging has led to devices in
      which color detection is not based on the use of physical color filters but
      relies on the wavelength dependence of the silicon absorption coefficient in the
      visible range. In some of these devices the responsivity of each color channel
      can be electrically tuned by changing the applied voltages. Exploiting this
      feature, this paper presents a new method of white balance that compensates for
      changes in the illuminant spectrum by changing accordingly the spectral
      responsivities, and therefore the native color space, of the detector. Different
      sets of responsivities corresponding to the different RGB color channels can be
      selected, depending on the illuminant, in order to keep the chromatic components
      of a white object independent of the illuminant. An implementation of this method
      with the transverse field detector, a color device with tunable spectral
      responsivities, is discussed. Experimental data show that the method is effective
      for three spectral sources that are strongly different from a chosen reference
      source. The color error in a perceptive color space after the subsequent color
      correction (specific for each set of base filters) does not change significantly
      in the tuning interval of interest for image acquisition.

PMID- 20035301
TI  - Analysis of semi-infinite periodic structures using a domain reduction technique.
AB  - A new boundary condition is introduced to calculate the effective impedance
      matrix of semi-infinite periodic structures such as photonic crystals and
      metamaterials, which leads to a reduction of the solution space. The obtained
      effective impedance matrix allows one to relate a matrix to a PC, which includes
      all of its properties in terms of reflection from its interface. For one
      dimensional photonic crystals or multilayer films, it is shown that a closed-form
      equation can be found for the effective impedance. For two-dimensional photonic
      crystals the impedance is obtained using the scattering matrices by solving a
      unilateral quadratic matrix equation. Several examples are outlined to validate
      the developed scheme. In the examples, the goal is mainly the computation of the
      reflection from a semi-infinite periodic structure when a plane wave illuminates
      its boundary.

PMID- 20035302
TI  - Distortion of binoculars revisited: does the sweet spot exist?
AB  - Sixty years ago, August Sonnefeld of Zeiss reported on observations with
      experimental telescopes. The goal of his investigation was to determine the ideal
      amount of distortion applied to optical instruments that are used in combination
      with the human eye. His studies were inconclusive and partially contradictory. We
      have picked up this problem once again, adopting a modern point of view about the
      human imaging process, and supported by computer graphics. Based on experiments
      with Helmholtz checkerboards, we argue that human imaging introduces a certain
      amount of barrel distortion, which has to be counterbalanced through the
      implementation of an equally strong pincushion distortion into the binocular
      design. We discuss in detail how this approach is capable of eliminating the
      globe effect of the panning binocular and how the residual pincushion distortion
      affects the image when the eye is pointing off-center. Our results support the
      binocular designer in optimizing his instrument for its intended mode of
      application, and may help binocular users and astronomers better understand their
      tools.

PMID- 20035303
TI  - Gaussian beam interaction with an air-gap Fizeau interferential wedge.
AB  - We describe a plane-wave-expansion approach for calculation of the fringe pattern
      in transmission and reflection for a Gaussian monochromatic beam. Both positive
      and negative incidence, at which the incident light beam undergoes multiple
      reflections within the wedge in direction of increasing or decreasing wedge
      thickness respectively, are analyzed. It is shown that the two opposite
      incidences of the light beam are described by the same mathematical expressions;
      i.e., the transmitted/reflected fringe pattern at positive incidence is a
      continuation of the pattern at negative incidence at some distance from the
      wedge. Numerical simulations are made for a high-reflectivity-coating air-gap
      Fizeau interferential wedge with apex angle of 5-100 microrad and thickness of 5
      500 microm as a useful optical element in laser resonator design. Experimental
      verification is also provided.

PMID- 20035304
TI  - Estimation of the phase derivative using an adaptive window spectrogram.
AB  - The paper introduces an adaptive-window-spectrogram-based method to directly
      estimate the phase derivative from a single fringe pattern. The proposed method
      relies on estimating the phase derivative using spectrogram peak detection for a
      set of different window lengths. Then the optimal window length is selected from
      the set by resolving the estimator's bias variance trade-off using the
      intersection of confidence intervals rule. Finally, the phase derivative estimate
      corresponding to the optimum window is selected. The method's applicability to
      phase derivative estimation is demonstrated using simulation and experimental
      results.

PMID- 20035305
TI  - Power carried by a nonparaxial TM beam.
AB  - In paraxial optics, the power carried by an optical beam can be accurately
      calculated by means of the integral of the squared modulus of its electric field
      over a plane transverse to the propagation axis. However, for nonparaxial
      electromagnetic beams, it is more appropriate to define the power carried by the
      beam by the integral of the longitudinal component of its time-averaged Poynting
      vector over a plane transverse to the propagation axis. In this paper, the
      expression of the power carried by a high-aperture transverse magnetic (TM) beam
      of any order is determined. The general expression of the power carried by a TM
      beam, which also applies for a transverse electric (TE) beam, is given in terms
      of a modified Struve function of order equal to an integer plus one-half.

PMID- 20035306
TI  - Binary mask optimization for forward lithography based on boundary layer model in
      coherent systems: erratum.

PMID- 20035307
TI  - Magnetic field integral equation analysis of surface plasmon scattering by
      rectangular dielectric channel discontinuities.
AB  - The scattering of a surface plasmon polariton (SPP) by a rectangular dielectric
      channel discontinuity is analyzed through a rigorous magnetic field integral
      equation method. The scattering phenomenon is formulated by means of the magnetic
      type scalar integral equation, which is subsequently treated through an entire
      domain Galerkin method of moments (MoM), based on a Fourier-series plane wave
      expansion of the magnetic field inside the discontinuity. The use of Green's
      function Fourier transform allows all integrations over the area and along the
      boundary of the discontinuity to be performed analytically, resulting in a MoM
      matrix with entries that are expressed as spectral integrals of closed-form
      expressions. Complex analysis techniques, such as Cauchy's residue theorem and
      the saddle-point method, are applied to obtain the amplitudes of the transmitted
      and reflected SPP modes and the radiated field pattern. Through numerical
      results, we examine the wavelength selectivity of transmission and reflection
      against the channel dimensions as well as the sensitivity to changes in the
      refractive index of the discontinuity, which is useful for sensing applications.

PMID- 20035308
TI  - Large-area maskless surface plasmon interference for one- and two-dimensional
      periodic nanoscale feature patterning.
AB  - A promising maskless surface-plasmon-interference nanoscale lithographic
      technique is proposed and demonstrated experimentally in this paper. One
      dimensional (grating-type) and two-dimensional (pillar-type) nanocale features
      were patterned on the photoresist layer using a 364 nm illumination wavelength
      source with a single exposure, by employing a custom-made prism layer
      configuration. Large-area patterns of grating lines and pillars with feature size
      approximately 90 nm were realized experimentally using this configuration.

PMID- 20035309
TI  - Christiansen filter realized by an odd smooth cylindrical lens.
AB  - The Christiansen filter that is realized by odd smooth cylindrical lenses is
      analyzed in detail. Several popular filtering functions are discussed. The
      corresponding lens profile functions are obtained by an inverse scattering
      theory, which enables the filter to synthesize a desired prescribed response
      function. This kind of Christiansen filter has a passband narrower than that of
      the traditional Christiansen filter. Three Christiansen filters centered at 545
      nm with full width at half-maximum of 2 nm are synthesized, and the approach to a
      better suppression of halos from the main transmission peak of the filters is
      presented in a systematic way.

PMID- 20035310
TI  - Fictitious diffracted waves in the diffraction theory of Kirchhoff.
AB  - The diffraction theory of Kirchhoff is applied to the semi-infinite aperture of a
      black half-screen. The derivative of the spherical Green's function is taken into
      account without any approximation. The uniformly evaluated scattering integral is
      compared with the physical optics solution. It is shown that the non-omitted term
      causes the existence of fictitious diffracted waves.

PMID- 20035311
TI  - Fast diffraction computation schema for multilayer crossed gratings containing
      layers with 1D periodicity.
AB  - The diffraction computation of crossed gratings is very slow compared with that
      of line-space gratings of the same size when using a modal method such as
      rigorous coupled wave analysis (RCWA) or the Chandezon coordinate transformation
      method. It is well known that the main bottleneck in terms of computation speed
      is the solution of an eigenproblem for each RCWA slice or interface in the case
      of the C-method. Even if the crossed grating contains layers that are periodic
      only in one direction, usually the full 2D problem has to be solved for this
      layer in order to connect it to the full system solution. In this paper, a
      computation schema is presented that takes advantage of the 1D periodicity of
      layers inside a 2D multilayer grating. This results in a considerable
      acceleration of the formulation and solution of the eigenproblem for these
      layers. With this new computation schema the total time required for 1D layers in
      a 2D layer stack can be greatly reduced.

PMID- 20035312
TI  - Canonical forms of depolarizing Mueller matrices.
AB  - It is shown that any depolarizing Mueller matrix can be reduced, through a
      product decomposition, to one of a total of two canonical depolarizer forms, a
      diagonal and a non-diagonal one. As a consequence, depolarizing Mueller matrices
      can be divided into Stokes diagonalizable and Stokes non-diagonalizable ones.
      Properties characteristic of the two canonical depolarizers are identified and
      discussed. Both canonical depolarizer forms are illustrated in experimental
      examples taken from the literature.

PMID- 20035313
TI  - Millimeter wave imaging system modeling: spatial frequency domain calculation
      versus spatial domain calculation.
AB  - Active millimeter wave imaging systems have become a promising candidate for
      indoor security applications and industrial inspection. However, there is a lack
      of simulation tools at the system level. We introduce and evaluate two modeling
      approaches that are applied to active millimeter wave imaging systems. The first
      approach originates in Fourier optics and concerns the calculation in the spatial
      frequency domain. The second approach is based on wave propagation and
      corresponds to calculation in the spatial domain. We compare the two approaches
      in the case of both rough and smooth objects and point out that the spatial
      frequency domain calculation may suffer from a large error in amplitude of 50% in
      the case of rough objects. The comparison demonstrates that the concepts of point
      spread function and f-number should be applied with careful consideration in
      coherent millimeter wave imaging systems. In the case of indoor applications, the
      near-field effect should be considered, and this is included in the spatial
      domain calculation.

PMID- 20035314
TI  - Identification and validation of a major QTL conferring crown rot resistance in
      hexaploid wheat.
AB  - Crown rot (CR), caused by various Fusarium species, is a chronic wheat disease in
      Australia. As part of our objective of improving the efficiency of breeding CR
      resistant wheat varieties, we have been searching for novel sources of
      resistance. This paper reports on the genetic control of one of these newly
      identified resistant genotypes, 'CSCR6'. A population derived from a cross
      between CSCR6 and an Australian variety 'Lang' was analyzed using two Fusarium
      isolates belonging to two different species, one Fusarium pseudograminearum and
      the other Fusarium graminearum. The two isolates detected QTL with the same
      chromosomal locations and comparable magnitudes, indicating that CR resistance is
      not species-specific. The resistant allele of one of the QTL was derived from
      'CSCR6'. This QTL, designated as Qcrs.cpi-3B, was located on the long arm of
      chromosome 3B and explains up to 48.8% of the phenotypic variance based on
      interval mapping analysis. Another QTL, with resistant allele from the variety
      'Lang', was located on chromosome 4B. This QTL explained up to 22.8% of the
      phenotypic variance. A strong interaction between Qcsr.cpi-3B and Qcsr.cpi-4B was
      detected, reducing the maximum effect of Qcrs.cpi-3B to 43.1%. The effects of
      Qcrs.cpi-3B were further validated in four additional populations and the
      presence of this single QTL reduced CR severity by up to 42.1%. The fact that
      significant effects of Qcrs.cpi-3B were detected across all trials with different
      genetic backgrounds and with the use of isolates belonging to two different
      Fusarium species make it an ideal target for breeding programs as well as for
      further characterization of the gene(s) involved in its resistance.

PMID- 20035315
TI  - Development and application of gene-based markers for the major rice QTL
      Phosphorus uptake 1.
AB  - Marker-assisted breeding is a very useful tool for breeders but still lags behind
      its potential because information on the effect of quantitative trait loci (QTLs)
      in different genetic backgrounds and ideal molecular markers are unavailable.
      Here, we report on some first steps toward the validation and application of the
      major rice QTL Phosphate uptake 1 (Pup1) that confers tolerance of phosphorus (P)
      deficiency in rice (Oryza sativa L.). Based on the Pup1 genomic sequence of the
      tolerant donor variety Kasalath that recently became available, markers were
      designed that target (1) putative genes that are partially conserved in the
      Nipponbare reference genome and (2) Kasalath-specific genes that are located in a
      large insertion-deletion (INDEL) region that is absent in Nipponbare. Testing
      these markers in 159 diverse rice accessions confirmed their diagnostic value
      across genotypes and showed that Pup1 is present in more than 50% of rice
      accessions adapted to stress-prone environments, whereas it was detected in only
      about 10% of the analyzed irrigated/lowland varieties. Furthermore, the Pup1
      locus was detected in more than 80% of the analyzed drought-tolerant rice
      breeding lines, suggesting that breeders are unknowingly selecting for Pup1. A
      hydroponics experiment revealed genotypic differences in the response to P
      deficiency between upland and irrigated varieties but confirmed that root
      elongation is independent of Pup1. Contrasting Pup1 near-isogenic lines (NILs)
      were subsequently grown in two different P-deficient soils and environments.
      Under the applied aerobic growth conditions, NILs with the Pup1 locus maintained
      significantly higher grain weight plant(-1) under P deprivation in comparison
      with intolerant sister lines without Pup1. Overall, the data provide evidence
      that Pup1 has the potential to improve yield in P-deficient and/or drought-prone
      environments and in diverse genetic backgrounds.

PMID- 20035316
TI  - Fine mapping the soybean aphid resistance gene Rag1 in soybean.
AB  - The soybean aphid (Aphis glycines Matsumura) is an important soybean [Glycine max
      (L.) Merr.] pest in North America. The dominant aphid resistance gene Rag1 was
      previously mapped from the cultivar 'Dowling' to a 12 cM marker interval on
      soybean chromosome 7 (formerly linkage group M). The development of additional
      genetic markers mapping closer to Rag1 was needed to accurately position the gene
      to improve the effectiveness of marker-assisted selection (MAS) and to eventually
      clone it. The objectives of this study were to identify single nucleotide
      polymorphisms (SNPs) near Rag1 and to position these SNPs relative to Rag1. To
      generate a fine map of the Rag1 interval, 824 BC(4)F(2) and 1,000 BC(4)F(3)
      plants segregating for the gene were screened with markers flanking Rag1. Plants
      with recombination events close to the gene were tested with SNPs identified in
      previous studies along with new SNPs identified from the preliminary Williams 82
      draft soybean genome shotgun sequence using direct re-sequencing and gene
      scanning melt-curve analysis. Progeny of these recombinant plants were evaluated
      for aphid resistance. These efforts resulted in the mapping of Rag1 between the
      two SNP markers 46169.7 and 21A, which corresponds to a physical distance on the
      Williams 82 8x draft assembly (Glyma1.01) of 115 kilobase pair (kb). Several
      candidate genes for Rag1 are present within the 115-kb interval. The markers
      identified in this study that are closely linked to Rag1 will be a useful
      resource in MAS for this important aphid resistance gene.

PMID- 20035317
TI  - Population parameters for resistance to Fusarium graminearum and Fusarium
      verticillioides ear rot among large sets of early, mid-late and late maturing
      European maize (Zea mays L.) inbred lines.
AB  - Infection of maize ears with Fusarium graminearum (FG) and Fusarium
      verticillioides (FV) reduces yield and quality by mycotoxin contamination.
      Breeding and growing varieties resistant to both Fusarium spp. is the best
      alternative to minimize problems. The objectives of our study were to draw
      conclusions on breeding for ear rot resistance by estimating variance components,
      heritabilities and correlations between resistances to FV and FG severity and to
      investigate different inoculation methods. In 2007 and 2008, three maturity
      groups (early, mid-late, late) each comprising about 150 inbred lines were tested
      in Germany, France, Italy, and Hungary according to their maturity group. They
      were silk channel inoculated by FG (early) and FV (all groups). In the late
      maturity group, additionally kernel inoculation was applied in a separate trial.
      The percentage of mycelium coverage on the ear was rated at harvest (0-100%).
      Significant (P < 0.01) genotypic variances of ear rot severity were found in all
      groups. Inoculation was superior to natural infection because of higher disease
      severities and heritabilities. In early maturing flints and dents, FG caused
      significantly (P < 0.01) higher ear rot severity than FV (61.7 and 55.1% FG vs.
      18.2 and 11.1% FV ear rot severity, respectively). FV inoculation in Southern
      Europe (mid-late, late) resulted in similar means between 10.3 and 14.0%.
      Selection is complicated by significant (P < 0.01) genotype x environment
      interactions. Correlation between FG and FV severity was moderate in flints and
      dents (r = 0.59 and 0.49, respectively) but lines resistant to both fungi exist.
      We conclude that chances for selecting improved European elite maize material
      within the existing germplasms is promising by multi-environmental inoculation
      trials.

PMID- 20035318
TI  - Predicting long-term recovery from depression in community settings in Western
      Europe: evidence from ODIN.
AB  - OBJECTIVE: To test the impact of socio-economic and psychological adversity and
      healthcare on long-term recovery from depression. METHOD: A community sample of
      347 people with depressive disorders was followed up after 9 years. Baseline
      socio-economic adversity, social support, healthcare use, and psychiatric history
      were identified. Respondents completed self-report instruments on current
      depressive status (Beck depression inventory) and longstanding psychosocial
      adversity (sexual, physical or emotional abuse). Univariate analyses tested for
      association between recovery and respondent characteristics. RESULTS: Follow-up
      was achieved for 182 (52%) of the sample, of whom 75 (41%) indicated recovery
      from depression. Psychological adversity definitely and socio-economic adversity
      probably were associated with lack of recovery. Baseline healthcare had no
      apparent impact on outcome. Rurality and support after life events were
      associated with recovery. History of depression was associated with non-recovery.
      CONCLUSION: Psychological adversity is, and socio-economic adversity may be,
      associated with long-term non-recovery from depression in community settings.

PMID- 20035319
TI  - Functional characterization of GDP-mannose pyrophosphorylase from Leptospira
      interrogans serovar Copenhageni.
AB  - Leptospira interrogans synthesizes a range of mannose-containing glycoconjugates
      relevant for its virulence. A prerequisite in the synthesis is the availability
      of the GDP-mannose, produced from mannose-1-phosphate and GTP in a reaction
      catalyzed by GDP-mannose pyrophosphorylase. The gene coding for a putative enzyme
      in L. interrogans was expressed in Escherichia coli BL21(DE3). The identity of
      this enzyme was confirmed by electrospray-mass spectroscopy, Edman sequencing and
      immunological assays. Gel filtration chromatography showed that the dimeric form
      of the enzyme is catalytically active and stable. The recombinant protein was
      characterized as a mannose-1-phosphate guanylyltransferase. S (0.5) for the
      substrates were determined both in GDP-mannose pyrophosphorolysis: 0.20 mM (GDP
      mannose), 0.089 mM (PPi), and 0.47 mM; and in GDP-mannose synthesis: 0.24 mM
      (GTP), 0.063 mM (mannose-1-phosphate), and 0.45 mM (Mg(2+)). The enzyme was able
      to produce GDP-mannose, IDP-mannose, UDP-mannose and ADP-glucose. We obtained a
      structural model of the enzyme using as a template the crystal structure of
      mannose-1-phosphate guanylyltransferase from Thermus thermophilus HB8. Binding of
      substrates and cofactor in the model agree with the pyrophosphorylases reaction
      mechanism. Our studies provide insights into the structure of a novel molecular
      target, which could be useful for detection of leptospirosis and for the
      development of anti-leptospiral drugs.

PMID- 20035321
TI  - Postural responses to unexpected perturbations of balance during reaching.
AB  - To study the interaction between feedforward and feedback modes of postural
      control, we investigated postural responses during unexpected perturbations of
      the support surface that occurred during forward reaching in a standing position.
      We examined postural responses in lower limb muscles of nine human subjects.
      Baseline measures were obtained when subjects executed reaching movements to a
      target placed in front of them (R condition) and during postural responses to
      forward and backward support-surface perturbations (no reaching, P condition)
      during quiet stance. Perturbations were also given at different delays after the
      onset of reaching movements (RP conditions) as well as with the arm extended in
      the direction of the target, but not reaching (P/AE condition). Results showed
      that during perturbations to reaching (RP), the initial automatic postural
      response, occurring around 100 ms after the onset of perturbations, was
      relatively unchanged in latency or amplitude compared to control conditions (P
      and P/AE). However, longer latency postural responses were modulated to aid in
      the reaching movements during forward perturbations but not during backward
      perturbations. Our results suggest that the nervous system prioritizes the
      maintenance of a stable postural base during reaching, and that later components
      of the postural responses can be modulated to ensure the performance of the
      voluntary task.

PMID- 20035322
TI  - Ischemic compression block attenuates mechanical hyperalgesia evoked from latent
      myofascial trigger points.
AB  - The aim of the present study is to test the hypothesis that large-diameter
      myelinated muscle afferents contribute to the pathophysiology of myofascial
      trigger points (MTrPs). The ischemic compression blockage (ICB) of large-diameter
      myelinated muscle afferents was obtained with a 7-cm-wide tourniquet applied
      around the upper arm proximal to the brachioradialis muscle in 20 healthy
      subjects. This study consisted of two randomized sessions with an interval of 1
      week in between each session. In one session, pressure pain threshold (PPT) and
      pressure threshold for eliciting referred pain (PTRP) were measured at an MTrP
      region in the brachioradialis muscle in one forearm. In another session, PPT was
      measured at a non-MTrP region in the brachioradialis muscle of the contralateral
      forearm at the time of pre-compression, 20 min following compression, and 10 min
      after decompression. The results showed that ICB, which mainly blocks large
      diameter myelinated muscle afferents, was associated with an increase in PPT and
      PTRP (all P < 0.001) at MTrP regions but not at non-MTrP regions. These results
      suggest that large-diameter muscle afferents may be involved in pain and
      mechanical hyperalgesia at MTrPs.

PMID- 20035323
TI  - Vestibular and neck somatosensory weighting changes with trunk extensor muscle
      fatigue during quiet standing.
AB  - The purpose of this study was to investigate whether vestibular and neck
      somatosensory weighting could change in conditions of trunk extensor muscle
      fatigue during quiet standing. To achieve this goal, 20 young healthy adults were
      asked to stand as still as possible in two conditions of No fatigue and Fatigue
      of trunk extensor muscles. In Experiment 1 (n = 10), the postural task was
      executed in two head conditions: Neutral and Head tilted backwards, recognised to
      degrade vestibular and neck somatosensory information. In Experiment 2 (n = 10),
      the postural task was executed in two stimulation conditions: No tactile
      stimulation and Tactile stimulation of the neck provided by the application of
      strips of adhesive bandage to the skin over and around the neck. The centre of
      foot pressure displacements (CoP) were recorded using a force platform. Results
      showed that (1) trunk extensor muscles fatigue increased CoP displacements under
      normal vestibular and neck somatosensatory conditions (Experiments 1 and 2), (2)
      this destabilizing effect of fatigue was exacerbated when vestibular and neck
      somatosensory information was altered (Experiment 1) and (3) this destabilizing
      effect of fatigue was suppressed when neck somatosensory information was neck was
      facilitated (Experiment 2). Taken together, results of Experiments 1 and 2 could
      be interpreted as an up-weighting of vestibular and neck somatosensory
      information for controlling posture during quiet standing following trunk
      extensor muscles fatigue.

PMID- 20035324
TI  - An event-related fNIRS investigation of Japanese word order.
AB  - Japanese is a free word-order language, and allows both subject-object-verb (SOV)
      and object-subject-verb (OSV) orders. Our previous study using near-infrared
      spectroscopy (NIRS) imaging revealed that OSV sentences induce more activation in
      the left frontal lobe than SOV sentences. The present study develops our previous
      experiment: (1) by adopting an event-related design, and (2) by using sentences
      involving the adverb naze 'why', which plays a prominent role in recent
      linguistic studies. The results of our new experiment indicated that the cerebral
      activation in O why SV sentences was significantly larger than that in S why OV
      sentences, in the right anterior prefrontal region, which is consistent with the
      assumption that O why SV order is derived from S why OV order. We speculate that
      the activation observed in the anterior prefrontal cortex during the processing
      of the sentences involving 'why' might be due to the processing of higher-order
      function in the cerebral cortex.

PMID- 20035325
TI  - Transformation of 17beta-estradiol mediated by lignin peroxidase: the role of
      veratryl alcohol.
AB  - Lignin peroxidases (LiPs) are a group of extracellular enzymes excreted by
      certain fungi, e.g., Phanerochaete chrysosporium. These fungi also produce
      veratryl alcohol (VA) as a secondary metabolite to regulate the performance of
      LiP. 17ss-Estradiol (E2) is a natural female hormone that is strongly endocrine
      disruptive when released to the natural environment. The widespread occurrence of
      E2 and related hormonal chemicals in soil and water environments has been
      identified, representing an emerging contamination of concern. We report in this
      study that E2 can be effectively transformed and removed through reactions
      mediated by LiP and such reactions are significantly enhanced in the presence of
      VA. We systematically investigated LiP activity and enzymatic reaction kinetics
      in systems having VA absent or present. The results suggest that VA enhanced the
      transformation and removal of E2 by the combination of two effects: (i)
      mitigating LiP inactivation and (ii) modifying the enzyme catalytic kinetics.
      These findings provide insights into an important pathway that may govern the
      environmental transformation of E2 and other emerging endocrine-disrupting
      contaminants of similar nature in the environment, and provide a basis for
      potential development and optimization of enzyme-based processes for remediation
      and removal of these contaminants.

PMID- 20035326
TI  - A longitudinal study of trends in blood dioxins and dioxin-like compounds levels
      in residents from two locations in Japan during 2002-2006.
AB  - To investigate the recent changes in background exposure to dioxin-related
      compounds, the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs),
      polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls
      (dl-PCBs) in the blood of individual residents in Japan were repeatedly examined.
      Twenty-six subjects (mean age, 52.7 +/- 1.8) from District A and 23 subjects
      (mean age, 56.1 +/- 1.2) from District B were longitudinally analyzed from 2002
      to 2006. District A is a rural area in Osaka prefecture, and District B is an
      urban area in Saitama prefecture. For the longitudinal analysis of these
      concentrations, we used the generalized estimating equation (GEE). The PCDD +
      PCDF concentrations decreased significantly between 2002 and 2006 (p < 0.0001),
      but the concentrations of dl-PCBs declined to a smaller degree over the 5-year
      period. A time x body mass index (BMI) interaction suggests that the reduction
      rate of blood PCDDs + PCDFs and dl-PCB concentrations in subjects with a BMI
      greater than the 75th percentile is lower than that of subjects with a BMI less
      than the 75th percentile from 2002 to 2004 over the 5-year period. From other
      reports on the dietary intake of PCDDs, PCDFs, and dl-PCBs in Japan, the total
      amount of daily dioxin intake decreased, but the percentage of dl-PCBs increased
      yearly in the first half of the 2000s. The reason for the difference in the 5
      year change in blood concentrations between PCDDs +PCDFs and dl-PCBs may be
      explained by the yearly change in the dietary dioxin intake.

PMID- 20035327
TI  - Cecorectal intussusception induced by a cecal hamartoma.
AB  - Cecorectal intussusception, a variant form of intussusception, occurs when the
      cecum enters through the entire course of colon and reaches to the rectum. This
      condition is rare but often associated with a pathologic lead point. Here, we
      report a 13-year-old boy, featuring insidious abdominal discomfort and
      constipation for 1 month, who developed cecorectal intussusception. Before
      surgical intervention, multi-detector row computed tomography with reconstructed
      images demonstrated the route of cecorectal intussusception and identified a
      cecal fat-containing tumor as the lead point. The patient received surgical
      reduction with resection of the cecal tumor. Final pathological diagnosis was a
      hamartoma of the cecum. The relevant literature pertaining to this condition is
      reviewed, and the possible pathophysiology of the condition discussed.

PMID- 20035328
TI  - Gastric clipping for morbid obesity: the initial results of a clinical trial.
AB  - OBJECTIVE: We inaugurated a clinical trial using laparoscopic gastric clipping to
      treat morbid obesity patients. We report the 2-year results. DESIGN: Ten patients
      with morbid obesity underwent laparoscopic gastric clipping to promote weight
      loss. A novel metallic clip was applied to the outside wall of the upper fundus
      of the stomach by a laparoscopic technique. The clip allowed a restricted passage
      of meals through a mucosa tunnel 0.4-0.6 cm in diameter. MEASUREMENTS: The body
      weight and feeding status of the patients were monitored periodically. Barium
      meal studies at 1 day and 2 years after the clipping were compared. RESULTS: Ten
      patients (3 men, 7 women) with body weight of 117 +/- 18.2 kg (101.8-156.5) and
      body mass index (BMI) 43.4 +/- 5.2 (40-56) were included. The gastric clips were
      successfully applied laparoscopically in all patients. The operation time ranged
      from 65 to 210 minutes and showed a learning curve. The excess body weight loss
      was progressive and long lasting postoperatively. The mean BMI and percentage of
      excess body weight loss at the 2-year period was 32.01 +/- 4.89 kg/m(2) and
      64.4%, respectively. The mean BMI 2 years after surgery was significantly
      decreased compared with that before surgery. Barium meal studies did not show
      significant sliding or migration of the clips at 2-year follow-up. No mortality
      or late complications occurred. CONCLUSIONS: Our results indicate that
      laparoscopic gastric clipping is a safe, simple, and effective treatment for
      patients with morbid obesity.

PMID- 20035329
TI  - Endovenous laser ablation as a treatment for postsurgical recurrent saphenous
      insufficiency.
AB  - The purpose of this study was to investigate the safety and efficacy of
      endovenous laser ablation as a treatment for recurrent symptomatic saphenous
      insufficiency occurring after saphenous vein ligation and stripping. A single
      center retrospective review of patients who received endovenous laser ablation as
      a treatment for recurrent symptomatic saphenous insufficiency after ligation and
      stripping between November 2003 and October 2006 was performed. Fifty-six
      insufficient saphenous systems were identified in 38 patients. Follow-up
      consisted of a clinical examination in all patients as well as selective lower
      extremity duplex ultrasound as clinically indicated. All 38 patients demonstrated
      complete closure of the insufficient saphenous vein by clinical examination
      and/or duplex ultrasound evaluation. Preoperative symptoms resolved after
      treatment in all 38 patients. No major complications were identified. Endovenous
      laser ablation of recurrent symptomatic saphenous venous insufficiency is a safe
      and effective treatment in patients who develop recurrent symptoms after
      saphenous vein ligation and stripping.

PMID- 20035330
TI  - Generation and characterization of thymidine/D-alanine auxotrophic recombinant
      Lactococcus lactis subsp. lactis IL1403 expressing BmpB.
AB  - Genetic engineering of Lactococcus lactis to produce a heterologous protein may
      cause potential risks to the environment despite the industrial usefulness of
      engineered strains. To reduce the risks, we generated three auxotrophic
      recombinant L. lactis subsp. lactis IL1403 strains expressing a heterologous
      protein, BmpB, using thyA- and alr-targeting integration vectors: ITD (thyA(
      )alr(+) bmpB(+)), IAD (thyA(+)alr(-)bmpB(+)), and ITDAD (thyA(-)alr(-) bmpB(+)).
      After construction of integration vectors, each vector was introduced into IL1403
      genome. Integration of BmpB expression cassette, deletion of thyA, and
      inactivation of alr were verified by using PCR reaction. All heterologous DNA
      fragments except bmpB were eliminated from those recombinants during double
      crossover events. By using five selective agar plates, we also showed thymidine
      auxotrophy of ITD and ITDAD and D-alanine auxotrophy of IAD and ITDAD. In M17G
      and skim milk (SYG) media, the growth of the three recombinants was limited. In
      MRS media, the growth of IAD and ITDAD was limited, but ITD showed a normal
      growth pattern as compared with the wild-type strain (WT). All the recombinants
      showed maximal BmpB expression at an early stationary phase when they were
      cultivated in M17G supplemented with thymidine and D-alanine. These results
      suggest that auxotrophic recombinant L. lactis expressing a heterologous protein
      could be generated to reduce the ecological risks of a recombinant L. lactis.

PMID- 20035331
TI  - Absolute risk reduction in osteoporosis: assessing treatment efficacy by number
      needed to treat.
AB  - Postmenopausal osteoporosis is a chronic condition due to decreased bone mass,
      leading to reduced bone strength and increased fracture risk. Currently available
      pharmacological treatments include antiresorptive agents (bisphosphonates and
      raloxifene) and bone-forming agents (strontium ranelate and two different
      parathyroid peptides). Comparison via reduction in relative risk of fracture may
      produce artificially high reductions in fracture risk for some agents. Responder
      analysis based on absolute risk reduction (ARR, the arithmetic difference between
      events rates with and without treatment over a fixed time) and a related
      parameter, number needed to treat (NNT, the number of patients needed to treat
      over a fixed time to prevent one event) may provide more reliable parameters. We
      reviewed placebo-controlled, randomized, double-blind, pivotal phase 3 trials
      employed as part of the regulatory process, in order to calculate ARRs and NNTs
      for vertebral and hip fracture over 3 years for antiosteoporotic agents currently
      available in Europe. The NNT values to prevent one vertebral fracture over 3
      years range from 9 for the strontium ranelate to 21 for ibandronate. NNT values
      for hip fracture over 3 years range from 48 for strontium ranelate to 91 for
      three of the bisphosphonates. Our analysis indicates that the bone-forming agent
      strontium ranelate may have the lowest NNT for the prevention of both vertebral
      and hip fracture. Responder analysis may enable translation of clinical trial
      results into guidance for routine clinical practice by indicating the amount of
      effort needed to prevent the same event in comparable populations with different
      treatment options.

PMID- 20035332
TI  - Primary Raynaud phenomenon and small-fiber neuropathy: is there a connection? A
      pilot neurophysiologic study.
AB  - The pathophysiologic factors of primary Raynaud phenomenon (RP) are unknown.
      Preliminary evidence from skin biopsy suggests small-fiber neuropathy (SFN) in
      primary RP. We aimed to quantitatively assess SFN in participants with primary
      RP. Consecutive patients with an a priori diagnosis of primary RP presenting to
      our outpatient rheumatology clinic over a 6-month period were invited to
      participate. Cases of secondary RP were excluded. All participants were required
      to have normal results on nailfold capillary microscopy. Assessment for SFN was
      accomplished with autonomic reflex screening, which includes quantitative
      sudomotor axonal reflex test (QSART), and cardiovagal and adrenergic function
      testing, thermoregulatory sweat test (TST), and quantitative sensory test (QST)
      for vibratory, cooling, and heat-pain sensory thresholds. Nine female
      participants with a median age of 38 years (range 21-46 years) and a median
      symptom duration of 9 years (range 5 months-31 years) were assessed. Three
      participants had abnormal results on QSART, indicating peripheral sudomotor
      autonomic dysfunction. Two participants had evidence of large-fiber involvement
      with heat-pain thresholds on QST. Heart rate and blood pressure responses to deep
      breathing, Valsalva maneuver, and 70 degrees  tilt were normal for all
      participants. Also, all participants had normal TST results. In total, three of
      the nine participants had evidence of SFN. The presence of SFN raises the
      possibility that a subset of patients with primary RP have an underlying,
      subclinical small-fiber dysfunction. These data open new avenues of research and
      therapeutics for this common condition.

PMID- 20035333
TI  - The effects of PDL-Ig on collagen-induced arthritis.
AB  - Programmed death ligand (PDL) is a new member of the B7 family of costimulatory
      molecules that specifically interacts with programmed death 1 (PD-1) expressed on
      activated T cells, B cells, and myeloid cells. Collagen II (CII)-induced
      arthritis (CIA) is an experimental model of arthritis that has been used to
      dissect the pathogenesis of human rheumatoid arthritis. In this study, we have
      investigated the effects of PDL-Ig on CIA. Administration of PDL-Ig significantly
      ameliorated the disease as assessed by clinical arthritis score and histology in
      the joints. Expression of proinflammatory cytokines, such as IL-17 and IL-23, in
      the serum was reduced by PDL-Ig treatment. These results showed a beneficial
      effect of PDL-Ig on CIA through anti-inflammatory actions and inhibition of cell
      proliferation in response to CII, suggesting that the PD-1-PDL pathway may be
      involved in the pathogenesis of CIA, and thus PDL-Ig may be a useful therapy for
      the improvement of human rheumatoid arthritis.

PMID- 20035334
TI  - Isolation and functional analysis of the Catharanthus roseus deacetylvindoline-4
      O-acetyltransferase gene promoter.
AB  - Madagascar periwinkle (Catharanthus roseus) produces many therapeutically
      valuable terpenoid indole alkaloids (TIAs), such as vinblastine and vincristine
      derived from the monomers vindoline and catharanthine. Deacetylvindoline-4-O
      acetyltransferase (DAT) is a key enzyme for the terminal step of vindoline
      biosynthesis. In this research, the DAT gene promoter was cloned, sequenced, and
      analyzed. An approximately 1,773 bp genomic DNA fragment of DAT promoter was
      obtained. Sequence analysis revealed that DAT promoter contained several
      potential regulatory elements which were involved in the regulation of gene
      expression. To investigate its function, the promoter fragments with 5' deletions
      and gain-of-function deletions were fused to GUS reporter gene, and their
      expressions were analyzed by transient expression in C. roseus cell suspensions.
      The regulatory activity of DAT promoter was identified with fluorescence
      quantitative assays. Three TGACG motifs and one inverted motif (CGTCA) between 
      808 and -1,086 bp in the DAT promoter were found to be involved in
      methyljasmonate signal transduction pathway.

PMID- 20035335
TI  - Estradiol interacts with an opioidergic network to achieve rapid modulation of a
      vocal pattern generator.
AB  - Estrogens rapidly regulate neuronal activity within seconds-to-minutes, yet it is
      unclear how estrogens interact with neural circuits to rapidly coordinate
      behavior. This study examines whether 17-beta-estradiol interacts with an
      opioidergic network to achieve rapid modulation of a vocal control circuit. Adult
      plainfin midshipman fish emit vocalizations that mainly differ in duration, and
      rhythmic activity of a hindbrain-spinal vocal pattern generator (VPG) directly
      establishes the temporal features of midshipman vocalizations. VPG activity is
      therefore predictive of natural calls, and 'fictive calls' can be elicited by
      electrical microstimulation of the VPG. Prior studies show that intramuscular
      estradiol injection rapidly (within 5 min) increases fictive call duration in
      midshipman. Here, we delivered opioid antagonists near the VPG prior to estradiol
      injection. Rapid estradiol actions on fictive calling were completely suppressed
      by the broad-spectrum opioid antagonist naloxone and the mu-opioid antagonist
      beta-funaltrexamine, but were unaffected by the kappa-opioid antagonist nor
      binaltorphimine. Unexpectedly, prior to estradiol administration, all three
      opioid antagonists caused immediate, transient reductions in fictive call
      duration. Together, our results indicate that: (1) vocal activity is modulated by
      opioidergic networks, confirming hypotheses from birds and mammals, and (2) the
      rapid actions of estradiol on vocal patterning depend on interactions with a mu
      opioid modulatory network.

PMID- 20035336
TI  - Central regulation of the pharyngeal and upper esophageal reflexes during
      swallowing in the Japanese eel.
AB  - We investigated the regulation of the pharyngeal and upper esophageal reflexes
      during swallowing in eel. By retrograde tracing from the muscles, the motoneurons
      of the upper esophageal sphincter (UES) were located caudally within the mid
      region of the glossopharyngeal-vagal motor complex (mGVC). In contrast, the
      motoneurons innervating the pharyngeal wall were localized medially within mGVC.
      Sensory pharyngeal fibers in the vagal nerve terminated in the caudal region of
      the viscerosensory column (cVSC). Using the isolated brain, we recorded 51
      spontaneously active neurons within mGVC. These neurons could be divided into
      rhythmically (n = 8) and continuously (n = 43) firing units. The rhythmically
      firing neurons seemed to be restricted medially, whereas the continuously firing
      neurons were found caudally within mGVC. The rhythmically firing neurons were
      activated by the stimulation of the cVSC. In contrast, the stimulation of the
      cVSC inhibited firing of most, but not all the continuously firing neurons. The
      inhibitory effect was blocked by prazosin in 17 out of 38 neurons. Yohimbine also
      blocked the cVSC-induced inhibition in five of prazosin-sensitive neurons. We
      suggest that the neurons in cVSC inhibit the continuously firing motoneurons to
      relax the UES and stimulate the rhythmically firing neurons to constrict the
      pharynx simultaneously.

PMID- 20035338
TI  - Human immunodeficiency virus and pregnancy.
AB  - Management of infection with human immunodeficiency virus (HIV) dramatically
      improved during the 1990s. The advent of high-performance quantitative HIV assays
      and highly active anti-retroviral therapy (HAART) were the two most important
      developments in HIV medicine. As a result, HIV mortality and morbidity have
      significantly reduced. This improvement in life quality and expectancy through
      the use of HAART has led to an increase in the number of HIV-infected patients
      wishing to have children. The mother-to-child transmission which was of major
      concern previously can now be significantly reduced by newer management
      strategies. This review stresses on the management of pregnancy in HIV.

PMID- 20035337
TI  - A 3-year Mediterranean-style dietary intervention may modulate the association
      between adiponectin gene variants and body weight change.
AB  - PURPOSE: Adiponectin gene variations have been associated with obesity. There are
      few interventional studies analyzing this association. The aim of this study was
      to analyze the effects of a nutritional intervention with Mediterranean-style
      diet and three (-4034A/C, +45T/G, and +276 G/T) adiponectin gene variants on 3
      year body weight changes in high cardiovascular risk patients. SUBJECTS AND
      METHODS: A total of 737 participants, aged 55-80 at high cardiovascular risk were
      assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with
      high intake of virgin olive oil (VOO) and the other with high intake of nuts.
      Anthropometric parameters were taken at baseline and after 3-year follow-up, and
      the genotyping of the -4034A/C, +45T/G, and +276 G/T polymorphisms was done.
      RESULTS: GG genotype of the +45T/G polymorphism was associated with 3-year higher
      body weight gain (B = 1.399; B = 0.043). TT genotype of the +276G/T polymorphism
      was linked to the highest 3-year body weight gain in men. Both Mediterranean
      diets appeared to reverse this effect (p for interaction = 0.053). CONCLUSION:
      Adiponectin gene variation appeared to be associated with 3-year body weight
      changes in a high cardiovascular risk population. This association may be
      modulated by a nutritional intervention with a Mediterranean-style diet.

PMID- 20035339
TI  - Neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients
      with unresectable, advanced stage epithelial ovarian cancer: a single centre
      experience.
AB  - BACKGROUND: Recent data has shown that the use of neoadjuvant chemotherapy (NAC)
      significantly reduces tumor burden before optimal cytoreductive surgery (CS) and
      is associated with an improved overall survival (OS). The aim of our study was to
      evaluate response to treatment and survival of patients with advanced epithelial
      ovarian cancer (EOC) who received NAC followed by interval cytoreductive surgery
      (ICS). METHODS: Fifty-two patients with advanced EOC treated with NAC followed by
      ICS were retrospectively analyzed. Response to NAC, progression-free survival
      (PFS), and OS were evaluated. By using univariate and multivariate analyses, the
      predicted survival rates by the factors were analyzed. RESULTS: Median age of
      patients at diagnosis were 62 years (range 33-77). The serous cell type was the
      most common histology (98%). The majority of patients (94%) received a
      combination therapy of paclitaxel and carboplatin. A median of four cycles of NAC
      was administered. At the end of NAC, the clinical complete response (CR) with
      normal clinical examination and normal serum CA 125 level was achieved in 40
      patients (77%). Moreover, a radiological CR and a radiological partial response
      were obtained in 35 patients (67%) and in 16 patients (31%), respectively. ICS
      was considered standard in 45 (86%) patients. Optimal cytoreduction could be
      achieved in 43 of 52 patients (83%). After ICS, pathological CR was established
      in 15 of 52 patients (29%). At the median follow-up of 25 months (range 9-102), 2
      year PFS and OS were 31 and 90%, respectively. The median PFS time was 13.3
      months (SE 1.1, 95% CI 11-15) and the median OS time was 47.5 months (SE 5.8, 95%
      CI 36.1-59). The univariate analysis showed that optimal or suboptimal
      cytoreduction and perioperative blood transfusion were important prognostic
      factors on OS for patients who received NAC. Patients treated with optimal
      cytoreduction had significantly better median OS (52.5 months, 95% CI 45-60) than
      patients who underwent suboptimal cytoreduction (24.2 months, 95% CI 11.3-37) (P
      = 0.001). Furthermore, the cytoreduction type (optimal vs. suboptimal), surgical
      procedure (standard vs. non-standard), and perioperative blood transfusion were
      independent prognostic factors of OS by multivariate analysis (chi (2) = 9.28, P
      = 0.002, HR 0.28, 95% CI 0.003-0.37; chi (2) = 4.44, P = 0.035, HR 0.15, 95% CI
      0.026-0.87; chi (2) = 9.24, P = 0.002, HR 0.75, 95% CI 0.014-0.79, respectively).
      CONCLUSIONS: This study demonstrates that NAC is associated with improved OS for
      patients with advanced EOC who received NAC followed by ICS. Additionally, our
      results showed that cytoreduction type, surgical procedure, and perioperative
      blood transfusion were independent prognostic indicators of OS for patients with
      advanced EOC who received NAC. Thereafter, NAC may be an alternative treatment to
      primary cytoreduction.

PMID- 20035340
TI  - KIT-positive primary small cell carcinoma of the endometrium: a case report with
      immunohistochemical and molecular genetic analysis of KIT and PDGFRA genes.
AB  - BACKGROUND: Primary small cell carcinoma of the endometrium is very rare, and
      there have been no reports on KIT and PDGFRA in endometrial small cell carcinoma.
      CASE REPORT: An 87-year-old woman was admitted to our hospital because of genital
      bleeding. Endometrial cytology and biopsy revealed small cell carcinoma. Scrutiny
      of the body showed stage III endometrial carcinoma with metastases. An
      immunohistochemical study of the biopsy specimens revealed positive reactions for
      synaptophysin, CD56, KIT, and PDGFRA, and negative reactions for cytokeratins,
      neuron-specific enolase, and chromogranin. A molecular genetic analysis using PCR
      direct sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and
      PDGFRA (exons 12 and 18) genes. The patient received chemotherapy and radiation,
      but showed a downhill course, and died of carcinomatosis 6 months after the
      initial presentation. CONCLUSION: The present case is the first reported case of
      primary small cell carcinoma of the endometrium with an examination of KIT and
      PDGFRA expressions and KIT and PDFGRA gene mutations.

PMID- 20035341
TI  - Near total thyroidectomy is an optimal treatment for graves' disease.
AB  - Surgical management of Graves' disease is still debated. We report our current
      experience with thyroidectomy for Graves' disease at a tertiary center. A
      retrospective database of 132 patients who underwent surgery for Graves' disease
      from January 1985 to December 2008 was collected. During that period, 16 patients
      underwent subtotal thyroidectomy and 116 patients underwent near total
      thyroidectomy. Eighty-seven patients (66%) underwent surgery for recurrent
      disease after medical therapy. Forty-five patients (34%) had surgery as a primary
      treatment, the indications were large goiter size in 22 (17%), patient preference
      in 19 (14%), and associated cold nodule in 3 (2%). The incidence of cancer was
      4.4%. Permanent hypoparathyroidism was observed in one patient who underwent a
      second surgery for recurrence. Unilateral transitory vocal cord palsy was
      observed in nine patients (7%), bilateral transitory vocal cord palsy was
      observed in one patient, and no definitive vocal cord palsy was observed. Two
      patients (1.5%) experienced post-operative hemorrhagia requiring surgical
      revision. Near total thyroidectomy for Graves' disease provides an immediate and
      definitive treatment with a low complication rate. Near total thyroidectomy
      offers an appropriate treatment for coexisting malignancy. This procedure can be
      safely recommended as a primary treatment, in experienced hands.

PMID- 20035343
TI  - Response of salivary peroxidase to exercise intensity.
AB  - Oral peroxidase, one of the most important salivary antioxidant enzymes, is
      subjected to alternation due to various body conditions. The aim of this study
      was to assess the effect of exercise intensity on salivary peroxidase activity.
      Using a randomized design, ten healthy male university students (mean age, 23.22;
      s (x) = 2.34 years) completed treadmill runs with initial velocity 6.73 km/h at
      the rate of 1.58 km/h increase every 3 min until exhaustion. Unstimulated whole
      saliva collected over a 5-min period in pre-weighed tubes before, immediately
      after exercise, and 1 h after exercise was analyzed for total protein and saliva
      peroxidase activity. The saliva flow rate ranged from 0.08 to 1.40 ml min(-1) at
      rest and was not significantly affected by the exercise. Peroxidase activity in
      each sample was measured using 4-amino antipyrine as substrate. In the
      incremental exhaustion run and also at 75% VO(2max), the secretion rates of
      peroxidase increased. No significant changes in saliva flow rate were observed in
      any treadmill run. Treadmill runs at 75% VO(2max) and to exhaustion increased the
      activity of peroxidase immediately after exercise which decreased after 1 h. It
      was concluded that short-duration, high-intensity exercise increases the activity
      rate of peroxidase despite no change in the saliva flow rate. These effects
      appear to be associated with changes in sympathetic activity and not the
      hypothalamic pituitary adrenal axis.

PMID- 20035342
TI  - Heavy ions, radioprotectors and genomic instability: implications for human space
      exploration.
AB  - The risk associated with space radiation exposure is unique from terrestrial
      radiation exposures due to differences in radiation quality, including linear
      energy transfer (LET). Both high- and low-LET radiations are capable of inducing
      genomic instability in mammalian cells, and this instability is thought to be a
      driving force underlying radiation carcinogenesis. Unfortunately, during space
      exploration, flight crews cannot entirely avoid radiation exposure. As a result,
      chemical and biological countermeasures will be an important component of
      successful extended missions such as the exploration of Mars. There are currently
      several radioprotective agents (radioprotectors) in use; however, scientists
      continue to search for ideal radioprotective compounds-safe to use and effective
      in preventing and/or reducing acute and delayed effects of irradiation. This
      review discusses the agents that are currently available or being evaluated for
      their potential as radioprotectors. Further, this review discusses some
      implications of radioprotection for the induction and/or propagation of genomic
      instability in the progeny of irradiated cells.

PMID- 20035344
TI  - Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy
      susceptibility.
AB  - The chromosomal region 10p13 has been linked to paucibacillary leprosy in two
      independent studies. The MRC1 gene, encoding the human mannose receptor (MR), is
      located in the 10p13 region and non-synonymous SNPs in exon 7 of the gene have
      been suggested as leprosy susceptibility factors. We determined that G396S is the
      only non-synonymous exon 7-encoded polymorphism in 396 unrelated Vietnamese
      subjects. This SNP was genotyped in 490 simplex and 90 multiplex leprosy families
      comprising 704 patients (47% paucibacillary; 53% multibacillary). We observed
      significant under-transmission of the serine allele of the G396S polymorphism
      with leprosy per se (P = 0.036) and multibacillary leprosy (P = 0.034). In a
      sample of 384 Brazilian leprosy cases (51% paucibacillary; 49% multibacillary)
      and 399 healthy controls, we observed significant association of the glycine
      allele of the G396S polymorphism with leprosy per se (P = 0.016) and
      multibacillary leprosy (P = 0.023). In addition, we observed a significant
      association of exon 7 encoded amino acid haplotypes with leprosy per se (P =
      0.012) and multibacillary leprosy (P = 0.004). Next, we tested HEK293 cells over
      expressing MR constructs (293-MR) with three exon 7 haplotypes of MRC1 for their
      ability to bind and internalize ovalbumin and zymosan, two classical MR ligands.
      No difference in uptake was measured between the variants. In addition, 293-MR
      failed to bind and internalize viable Mycobacterium leprae and BCG. We propose
      that the MR-M. leprae interaction is modulated by an accessory host molecule of
      unknown identity.

PMID- 20035345
TI  - A study of surgeons' postural muscle activity during open, laparoscopic, and
      endovascular surgery.
AB  - BACKGROUND: Different surgical procedures impose different physical demands on
      surgeons and high prevalence rates of neck and shoulder pain have been reported
      among general surgeons. Past research has examined electromyography in surgeons
      mainly during simulated conditions of laparoscopic and open surgery but not
      during real-time operations and not for long durations. The present study
      compares the neck-shoulder muscle activities in three types of surgery and
      between different surgeons. The relationships of postural muscle activities to
      musculoskeletal symptoms and personal factors also are examined. METHODS: Twenty
      five surgeons participated in the study (23 men). Surface electromyography (EMG)
      was recorded in the bilateral cervical erector spinae, upper trapezius, and
      anterior deltoid muscles during three types of surgical procedures: open,
      laparoscopic, and endovascular. In each procedure, EMG data were captured for 30
      min to more than 1 h. The surgeons were asked to rate any musculoskeletal
      symptoms before and after surgery. RESULTS: The present study showed
      significantly higher muscle activities in the cervical erector spinae and upper
      trapezius muscles in open surgery compared with endovascular and laparoscopic
      procedures. Muscle activities were fairly similar between endovascular and
      laparoscopic surgery. The upper trapezius usually has an important role in
      stabilizing both the neck and upper limb posture, and this muscle also recorded
      higher activities in open compared with laparoscopic and endovascular surgeries.
      Surgeons reported similar degrees of musculoskeletal symptoms in open and
      laparoscopic surgeries, which were higher than endovascular surgery. CONCLUSIONS:
      The present study showed that open surgery imposed significantly greater physical
      demands on the neck muscles compared with endovascular and laparoscopic
      surgeries. This may be due to the lighter manual task demands of these minimally
      invasive surgeries compared with open procedures, which generally required more
      dynamic movements and more forceful exertions.

PMID- 20035346
TI  - The feasibility of scarless single-port transumbilical total laparoscopic
      hysterectomy: initial clinical experience.
AB  - OBJECTIVE: The purpose of the present study is to demonstrate the feasibility of
      single-port transumbilical laparoscopic surgery (SPLS) for hysterectomy and
      elaborate on our experience in order to introduce the single-port approach for
      gynecologic surgery. METHODS: Between August 2008 and February 2009, 30 patients
      who initially planned to undergo single-port laparoscopic surgery at Yonsei
      University Health System in Seoul, Korea were enrolled in this study. The authors
      used a single-port three-channel system with a wound retractor, surgical gloves,
      and one 10/11-mm and two 5-mm trocars. All surgical procedures were performed
      with 30 degrees , 5-mm laparoscope, conventional laparoscopic instruments, and
      the LigaSure system (Valleylab, Boulder, CO, USA). Patient characteristics and
      surgical outcomes were prospectively evaluated. A visual analog score (VAS) scale
      was used to measure postoperative pain. RESULTS: Twenty-nine of 30 patients
      underwent single-port laparoscopic surgery without conversion to laparotomy or
      conventional laparoscopic hysterectomy. Median operative time was 100 min (57-155
      min), median blood loss was 100 ml (10-400 ml), median postoperative hospital
      stay was 3 days (2-6 days), and median weight of resected uteri was 167 g (45-482
      g). VAS scoring of pain at 6, 24, and 48 h after surgery was 4, 3, and 2,
      respectively. There were no operative complications. CONCLUSION: SPLS is a
      feasible approach for hysterectomy in terms of operative time, complication
      rates, and cosmetic results. However, the possible benefits for patients such as
      better cosmetic outcomes, reduced pain, and lower complication rates should be
      evaluated in randomized prospective studies.

PMID- 20035347
TI  - Creation of pneumoperitoneum: noninvasive monitoring of clinical effects of
      elevated intraperitoneal pressure for the insertion of the first trocar.
AB  - AIM: The aim of this work is to analyze, by means of noninvasive monitoring, the
      clinical effects of high intraperitoneal pressure for enough time to insert the
      first trocar. METHODS: Sixty-seven patients without significant lung problems
      were randomly divided into groups P12 (n = 30, maximum intraperitoneal pressure
      12 mmHg) and P20 (n = 37, maximum intraperitoneal pressure 20 mmHg). A Veress
      needle was inserted into the left hypochondrium for creation of pneumoperitoneum.
      The parameters evaluated were heart rate (HR, in bpm), arterial oxygen saturation
      (SaO(2), expressed as percentage of hemoglobin saturated with oxygen), end-tidal
      CO(2) (ETCO(2), in mmHg), mean arterial pressure (MAP, in mmHg), and
      intratracheal pressure (ITP, in cmH(2)O). Clinical parameters were evaluated in
      both groups at time point 0 (TP0, before CO(2) insufflation), time point 1 (TP1,
      when intraperitoneal pressure of 12 mmHg was reached in both groups), time point
      2 (TP2, 5 min after reaching intraperitoneal pressure of 12 mmHg in group P12 and
      of 20 mmHg in group P20), and time point 3 (TP3, 10 min after reaching
      intraperitoneal pressure of 12 mmHg in group P12 and 10 min after TP1 in group
      P20, when intraperitoneal pressure decreased from 20 to 12 mmHg). Values outside
      of the normal range or occurrence of atypical phenomena suggestive of organic
      disease indicated clinical changes. RESULTS: Statistically significant
      differences were observed between the two groups regarding HR, MAP, ETCO(2), and
      ITP. No significant clinical changes were observed. CONCLUSIONS: Transitory, high
      intraperitoneal pressure (20 mmHg for 5 min) for insertion of the first trocar
      resulted in changes in HR, MAP, ETCO(2), and ITP that were within the normal
      range, and no adverse clinical effects were observed. Therefore, the use of
      transitory, high intraperitoneal pressure is recommended to prevent iatrogenic
      injury during blind insertion of the first trocar. Nevertheless, it is not clear
      that this method would be safe in patients with moderate to severe chronic
      obstructive pulmonary disease.

PMID- 20035348
TI  - Comparison of video-assisted thyroidectomy and traditional thyroidectomy for the
      treatment of papillary thyroid carcinoma.
AB  - BACKGROUND: There is concern regarding the oncological effectiveness of minimally
      invasive video-assisted thyroidectomy (VAT) for thyroid carcinoma. This study
      compared the surgical results of VAT and traditional thyroidectomy in patients
      with small papillary thyroid carcinomas (PTC). METHODS: Of 44 patients with PTC
      offered the choice between VAT and traditional thyroidectomy, 21 underwent VAT
      and 23 underwent traditional thyroidectomy. Residual thyroid tissue and function
      were assessed postoperatively by measuring thyroid-stimulating hormone (TSH), T4,
      thyroglobulin, and anti-thyroglobulin antibody levels and with sonographic
      examination. RESULTS: Operative time, maximum tumor size, number of positive
      lymph nodes, and TSH and T4 levels 4 weeks postoperatively were similar in the
      two groups (all p > 0.05). Patients in the traditional thyroidectomy group had
      significantly higher postoperative serum thyroglobulin levels 4 weeks after
      surgery than did patients in the VAT group (5.4 versus 0.5 ng/ml, respectively; p
      = 0.007). Postoperative ultrasonography showed no residual thyroid tissue or
      evidence of recurrence in any of the patients. The median follow-up period was 60
      months (range 31-77 month) for the VAT group and 53 months (range 31-80 months)
      for the traditional thyroidectomy group. Thyroglobulin levels of all patients in
      both groups decreased to <0.2 ng/ml at last follow-up. CONCLUSIONS: VAT is safe
      and effective for the treatment of small papillary thyroid carcinomas, and has
      similar oncological effectiveness to traditional thyroidectomy.

PMID- 20035350
TI  - Video. Endoscopic minimally invasive thyroidectomy: first clinical experience.
AB  - BACKGROUND: Since Theodor Kocher reduced the mortality rate of thyroidectomy from
      the 40% reported by Billroth to 0.2% in 1895, a collar incision with open removal
      of the thyroid gland is the standard procedure. In the past decade, efforts were
      made to reduce incision size and surgical access trauma by the use of endoscopic
      techniques. A first attempt was replacement of the central "Kocher incision" with
      lateral neck incisions and endoscopic removal of a thyroid lobe by Huscher on 8
      July 1996. This lateral access was limited to removing only one lobe of the
      gland. The most common technique to date is the one developed by Miccoli et al.
      These authors reduced the incision to a size of 20 to 25 mm and operated on the
      thyroid by the use of video-endoscopic assistance (MIVAT). Several groups have
      described an access outside the frontal neck region via a chest, axillary, or
      combined axillary bilateral breast approach. These accesses only moved the entry
      point from the frontal neck region to other regions, where they are still
      visible. The aforementioned minimally invasive approach and the conventional open
      approach do not respect anatomically given surgical planes and may therefore
      result in patient complaints, especially swallowing disorders after the scaring
      of the subcutaneous tissues. These extracervical approaches are associated with
      an extensive dissection in the access area and thus are maximally invasive.
      Therefore, we developed an exclusively endoscopic approach for thyroid resection
      with standard instruments used for minimally invasive surgery (diameter, 3.5 mm).
      This endoscopic minimally invasive thyroidectomy (eMIT) technique was evaluated
      carefully by anatomic and cadaver dissections as well as ultrasound studies for
      technical realization and needs for instrument design. To verify the safety and
      feasibility of the method, an animal trial was conducted in August 2008. Surgery
      was performed securely on five pigs, with very low blood loss. The postoperative
      behavior with special regard for feeding and pain reaction was normal until
      dissection. Especially, no local infection in the oral cavity or cervical spaces
      was noted. METHODS: All the trials of eMIT showed good results, so we went on to
      its first clinical application in the spring of 2009. A 53-year-old man had
      experienced dysphagia for more than a year. During routine diagnosis, the thyroid
      hormones T3, T4, and TSH were controlled and within normal levels. Thyroid
      scintigraphy, B-mode ultrasound examination, and laryngoscopy were performed
      preoperatively. An euthyroid nodular chance of the right hemithyroid with a
      beginning focal autonomy was diagnosed. After the patient's informed consent was
      received, surgery was performed on 18 March 2009 in an interdisciplinary
      collaboration between a general surgeon and a head and neck surgeon. The first
      incision was made in the midline sublingually. A 5-mm trocar was directed through
      the floor of the mouth muscles into the subplatysmal layer and positioned at the
      level of the cricoid. Carbon dioxide then was insufflated at 6 mmHg to build a
      tent above the thyroid gland. Next, a second trocar for insertion of the surgical
      instruments was placed over a vestibular incision into the same subplatysmal
      layer. This allowed the surgical field to be visualized fully and dissected with
      3.7-mm standard minimally-invasive instruments. A third trocar for surgical
      instruments then was placed through an incision on the left side of the vestibule
      of the mouth. After a midline incision of the linea alba, the fibrous capsule of
      the thyroid gland could been seen. The isthmus then was prepared in total. Next,
      the strap muscles above the right hemithyroid were prepared, showing the right
      upper pole. With the Harmonic scalpel, the isthmus was divided on the left side.
      The gland was loosened from the trachea and the adjacent lamella. The vessels of
      the upper pole were divided by Ultracision (Ethicon-Endosurgery, Cincinnate/Ohio,
      USA). Under the adjacent lamella, the recurrent nerve was visualized and
      stimulated. Neuro-monitoring showed an intact function of the nerve. Finally, the
      lower pole was detached, allowing the thyroid to be freely movable. Recovery of
      the tumor was performed through the median trocar incision after the optic device
      was moved through a lateral trocar. The tumor volume was 5.5 ml. The operation
      site was checked for bleedings and lavaged with sodium chloride. After removal of
      all the trocars, the wounds were sutured with self-resorbable sutures. Plaster
      tape was applied for 24 h. No direct postoperative complications occurred.
      Postoperative histology showed a colloidal struma. RESULTS: The floor of the
      mouth healed well, with no local infections at the incision sites or in the
      cervical spaces. Vocal cord function, evaluated by direct video-laryngoscopy, was
      normal. The patient had minimal swelling of the neck and a small hematoma, which
      resolved within 2 weeks. He had neither swallowing disorders nor oral pain. His
      preoperative dysphagia was gone, and he left the clinic 2 days after surgery
      without any complaints. CONCLUSION: With the development of an exclusively
      endoscopic approach for thyroid resection (eMIT) and its first clinical
      application, we could show the safety and feasibility of another natural orifice
      surgery procedure. One major concern before surgery was possible infection of the
      cervical spaces by introduction of oral flora to these regions. Investigating
      this infection risk, Hong and Yang evaluated the surgical results associated with
      the intraoral approach for submandibulectomy in a series of 77 cases of chronic
      sialadenitis and benign mixed tumors. The infection rate was 2.6% (2 patients)
      compared with 7.3% in a control group of 251 patients who underwent a
      transcervical procedure. Therefore, we estimated the infection risk to be lower
      than with conventional transcervical approaches. The clear advantages of this
      technique are its minimally invasive character, its reduction of surgical trauma,
      its direct access to surgical planes and spaces, its avoidance of swallowing
      disorders and postoperative dysphagia, and finally, its avoidance of any skin
      scars. Further trials are already being conducted.

PMID- 20035349
TI  - Total laparoscopic liver resection for hepatocellular carcinoma located in all
      segments of the liver.
AB  - BACKGROUND: Laparoscopic liver resection (LLR) is still not a well-established
      treatment modality for hepatocellular carcinoma (HCC). Moreover, most reported
      cases have been limited to tumors in the anterolateral (AL) segments (segments 2,
      3, 4b, 5, and 6). We evaluated clinical and oncologic outcomes after LLR for HCC
      located in all segments, including lesions located in the posterosuperior (PS)
      segments (segments 1, 4a, 7, and 8). METHODS: This retrospective study included
      69 patients who had undergone LLR for HCC between September 2003 and November
      2008. The patients were divided into two groups (group AL and group PS) according
      to tumor location. The clinical data of the two groups were retrospectively
      analyzed. RESULT: There was no postoperative mortality. Fifteen patients (21.7%)
      experienced 19 postoperative complications. During a median follow-up period of
      21.3 months, recurrence was detected in 21 (30.4%) patients. The 3-year overall
      survival rate and disease-free survival rate were 90.4 and 60.4%, respectively.
      There was no difference in clinicopathologic characteristics between the two
      groups except for a male predominance in group PS (p = 0.021) and that there were
      more patients with thrombocytopenia in group AL (p = 0.001). Although group PS
      patients had longer operative time (p = 0.001) and longer postoperative hospital
      stay (p = 0.039), along with a tendency toward a higher rate of open conversion
      (p = 0.054) and greater blood loss (p = 0.068), there was no significant
      difference in rates of postoperative complications (p = 0.375), recurrence (p =
      0.740), 3-year overall survival (p = 0.237) or disease-free survival (p = 0.411)
      between the two groups. CONCLUSIONS: Our experience shows that LLR can be safely
      performed in selected patients with HCC located in all segments of the liver,
      including the posterosuperior segments, with acceptable postoperative morbidity
      and oncologic results.

PMID- 20035351
TI  - Pancreas-hanging maneuver in laparoscopic pancreaticoduodenectomy: a new
      technique for the safe resection of the pancreas head.
AB  - BACKGROUND: Laparoscopic pancreaticoduodenectomy (PD) is challenging, and the
      performance of successful laparoscopic PD has been limited. The dissection of the
      pancreatic head from the right aspect of the portal vein and the superior
      mesenteric artery is one of the most difficult procedures in laparoscopic PD.
      METHODS: For the safe dissection of the pancreatic head during laparoscopic PD,
      we developed a novel "pancreas-hanging maneuver" technique. Nine patients
      underwent this new surgical procedure between December 2008 and June 2009 during
      the course of laparoscopic pylorus-preserving PD. RESULTS: The pancreas-hanging
      maneuver can ensure suitable tension, surgical field, and laparoscopic view for
      the resection of the pancreatic head during PD. Mean intraoperative blood loss
      was 642 ml (range = 420-780 ml). CONCLUSION: This new surgical procedure can
      provide good tension and an appropriate laparoscopic view with a suitable
      surgical field for safely dissecting the pancreas head from the major mesenteric
      vessels during laparoscopic PD.

PMID- 20035352
TI  - Providing more through less: current methods of retraction in SIMIS and NOTES
      cholecystectomy.
AB  - BACKGROUND: As the field of minimally invasive surgery continues to develop,
      surgeons are confronted with the challenge of performing conventional
      laparoscopic surgeries through fewer incisions while maintaining the same degree
      of safety and surgical efficiency. Most of these methods involve elimination of
      the ports previously designated for retraction. As a result, minimally invasive
      surgeons have been forced to develop minimally invasive and ingenious methods for
      providing adequate retraction for these procedures. Herein we present our
      experience using endoloops and internal retractors to provide retraction during
      Single Incision Minimally Invasive Surgery (SIMIS) and Natural Orifice
      Transluminal Endoscopic Surgery (NOTES) cholecystectomy. We also present a review
      of the alternative retraction methods currently being employed for these
      surgeries. METHODS: SIMIS was performed on 20 patients and NOTES was performed on
      5 patients at our institution. Endoloops or internal retractors were used to
      provide retraction for all SIMIS procedures. Internal retractors provided
      retraction for all NOTES procedures. RESULTS: Successful cholecystectomy was
      accomplished in all cases. One SIMIS surgery required conversion to standard
      laparoscopy due to complex anatomy. There were no intraoperative complications.
      Although adequate retraction was accomplished in all cases, the internal
      retractors were found to provide superior and more versatile retraction compared
      to that of endoloops. CONCLUSION: Adequate retraction greatly simplifies SIMIS
      and NOTES surgery. Endograb internal retractors were easy to use and were found
      to provide optimal retraction and exposure during these procedures without
      complications.

PMID- 20035353
TI  - The RAPID protocol enhances patient recovery after both laparoscopic and open
      colorectal resections.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) programs can accelerate
      recovery and shorten the hospital stay after colorectal resections. The RAPID
      (remove, ambulate, postoperative analgesia, introduce diet) protocol is a
      simplified ERAS program that consists of a simplified, user-friendly single-page
      pro forma schedule. This study aimed to evaluate the impact of the RAPID protocol
      on patients undergoing both laparoscopic and open colorectal resections in two
      specialized colorectal units. METHODS: A prospective, two-center study assessed
      117 age-matched patients undergoing open or laparoscopic colorectal resection to
      compare the postoperative course for patients using the RAPID protocol with those
      treated in a traditional manner. RESULTS: Of the 117 patients studied, 70
      underwent laparoscopic resection (55 with the RAPID protocol) and 47 underwent
      open resection (25 with the RAPID protocol). Patients undergoing laparoscopic
      resections with the RAPID protocol had a significantly shorter hospital stay (p =
      0.01) and tolerance of a full diet (p = 0.002). Similarly, patients undergoing
      open resections with the RAPID protocol also have a significantly shorter
      hospital stay (p = 0.04). CONCLUSION: The RAPID protocol is a user-friendly,
      easy, and effective tool that facilitates earlier tolerance of diet and discharge
      from the hospital for patients undergoing laparoscopic or open colorectal
      resections.

PMID- 20035354
TI  - Early gastric cancer management.

PMID- 20035355
TI  - Single-incision laparoscopic cholecystectomy: initial evaluation of a large
      series of patients.
AB  - BACKGROUND: Findings have shown that single-incision laparoscopic cholecystectomy
      (SILC) is feasible and reproducible. The authors have pioneered a two-trocar SILC
      technique at the University of Texas Southwestern. Their results for 100 patients
      are presented. METHODS: From January 2008 to March 2009, 100 patients with
      symptomatic gallbladder disease underwent SILC through a 1.5- to 2-cm umbilical
      incision using a two-port (5-mm) technique. For nearly all the patients, a 30
      degrees angled scope was used. The gallbladder was retracted, with two or three
      sutures placed along the gallbladder. These sutures were either fixated
      internally or placed through the abdominal wall to obtain a critical view of
      Calot's triangle. The SILC procedure was performed using standard technique with
      5-mm reticulating or conventional laparoscopic instruments. The cystic duct and
      artery were well visualized, clipped, and divided. Cholecystectomy was completed
      with electrocautery, and the specimen was retrieved through the umbilical
      incision. RESULTS: In this series, 80 women (85%) and 15 men (15%) with an
      average age of 33.8 years (range, 17-66 years) underwent SILC. Their mean BMI was
      29.8 kg/m(2) (range, 17-42.5 kg/m(2)), and 39% of these patients had undergone
      previous abdominal surgery. The mean operative time was 50.8 min (range, 23-120
      min). The mean estimated blood loss was 22.3 ml (range, 5-125 ml), and 5% of the
      patients had an intraoperative cholangiogram. There were no conversions of the
      SILC technique. A two-trocar technique was feasible for 87% of the patients. For
      the remaining patients, either a three-channel port or three individual trocars
      were required. A SILC technique was used for 5% of the patients to manage acute
      cholecystitis or gallstone pancreatitis. CONCLUSION: The SILC technique with a
      two-trocar technique is safe, feasible, and reproducible. The operating times are
      reasonable and can be lessened with experience. Even complex cases can be managed
      with this technique. Excellent exposure of the critical view was obtained in all
      cases. The SILC procedure is becoming the standard of care for most of the
      authors' elective patients with gallbladder disease. Clinical trials are
      warranted before the SILC technique is adopted universally.

PMID- 20035356
TI  - Clinical usefulness of 18F-FDG PET-CT for patients with gallbladder cancer and
      cholangiocarcinoma.
AB  - BACKGROUND: Reports concerning the clinical usefulness of (18)F 2-fluoro-2-deoxy
      D: -glucose integrated positron emission and computed tomography ((18)F-FDG PET
      CT) for patients with gallbladder cancer and cholangiocarcinoma are relatively
      scarce. The purpose of this study was to assess the diagnostic value of PET-CT in
      relation to a conventional imaging modality, multidetector row CT (MDCT), for
      patients with gallbladder cancer and cholangiocarcinoma. METHODS: Ninety-nine
      patients with suspected gallbladder cancer and cholangiocarcinoma who underwent
      both PET-CT and MDCT for initial staging were included in our study. The results
      of these two imaging modalities for evaluating primary tumors, regional lymph
      nodes and distant metastases were compared with the final diagnoses based on
      pathological or clinical findings. RESULTS: A maximum standardized uptake value
      (SUV(max)) of 3.65 was found to be the best cutoff value for detecting a
      malignant tumor. The overall values for the sensitivities, specificities,
      positive predictive values (PPVs), negative predictive values (NPVs) and the
      accuracies of PET-CT and MDCT for the detection of a primary tumor were 90.2,
      70.6, 93.7, 60.0, 86.9% and 84.2, 70.6, 93.2, 48.0, 81.8%, respectively. PET-CT
      demonstrated no significant advantage over MDCT for the diagnosis of a primary
      tumor. PET-CT showed a significantly higher PPV (94.1 vs. 77.5%, P = 0.04) than
      that found for MDCT in the diagnosis of regional lymph node metastasis.
      Additionally, PET-CT showed a significantly higher sensitivity (94.7 vs. 63.2%, P
      = 0.02) than that found for MDCT in the diagnosis of distant metastasis.
      CONCLUSIONS: PET-CT is valuable for detecting regional lymph node involvement and
      unsuspected distant metastases that are not diagnosed by MDCT.

PMID- 20035357
TI  - Clinical results and development of heterotopic ossification in total cervical
      disc replacement during a 4-year follow-up.
AB  - Cervical total disc replacement (CTDR) aims to decrease the incidence of adjacent
      segment disease through motion preservation in the operated disc space. Ongoing
      data collection and increasing number of studies describing heterotopic
      ossification (HO) resulting in decreased mobility of implants, forced us to
      carefully evaluate our long-term clinical and morphological results of patients
      with CTDR. We present the first 54 consecutive patients treated with 65 ProdiscC
      prostheses during a 12-month period (2/2004-3/2005). All patients signed an
      informed consent and were included in prospective long-term study approved by
      hospital ethical committee. The 1- and 2-year follow-up analysis were available
      for all patients included and 4-year results for 50 patients (60 implants).
      Clinical (neck disability index-NDI, visual analog scale-VAS) and radiological
      follow-up was conducted at 1-, 2- and 4-years after the procedure. The
      Mehren/Suchomel modification of McAfee scale was used to classify the appearance
      of HO. Mean preoperative NDI was 34.5%, VAS for neck pain intensity 4.6 and VAS
      for arm pain intensity 5.0. At 1-, 2- and 4-year follow-up, the mean NDI was
      30.7, 27.2, and 30.4, mean VAS for neck pain intensity 2.5, 2.1 and 2.9 and mean
      VAS for arm pain intensity pain 2.2, 1.9 and 2.3, respectively. Significant HO
      (grade III) was present in 45% of implants and segmental ankylosis (grade IV) in
      another 18% 4 years after intervention. This finding had no clinical consequences
      and 92% of patients would undergo the same surgery again. Our clinical results
      (NDI, VAS) are comparable with fusion techniques. Although, advanced non-fusion
      technology is used, a significant frequency of HO formation and spontaneous
      fusion in cervical disc replacement surgery must be anticipated during long-term
      follow-up.

PMID- 20035358
TI  - Prognostic factors for perceived recovery or functional improvement in non
      specific low back pain: secondary analyses of three randomized clinical trials.
AB  - The objective of this study was to report on secondary analyses of a merged trial
      dataset aimed at exploring the potential importance of patient factors associated
      with clinically relevant improvements in non-acute, non-specific low back pain
      (LBP). From 273 predominantly male army workers (mean age 39 +/- 10.5 years,
      range 20-56 years, 4 women) with LBP who were recruited in three randomized
      clinical trials, baseline individual patient factors, pain-related factors, work
      related psychosocial factors, and psychological factors were evaluated as
      potential prognostic variables in a short-term (post-treatment) and a long-term
      logistic regression model (6 months after treatment). We found one dominant
      prognostic factor for improvement directly after treatment as well as 6 months
      later: baseline functional disability, expressed in Roland-Morris Disability
      Questionnaire scores. Baseline fear of movement, expressed in Tampa Scale for
      Kinesiophobia scores, had also significant prognostic value for long-term
      improvement. Less strongly associated with the outcome, but also included in our
      final models, were supervisor social support and duration of complaints (short
      term model), and co-worker social support and pain radiation (long-term model).
      Information about initial levels of functional disability and fear-avoidance
      behaviour can be of value in the treatment of patient populations with
      characteristics comparable to the current army study population (e.g.,
      predominantly male, physically active, working, moderate but chronic back
      problems). Individuals at risk for poor long-term LBP recovery, i.e., individuals
      with high initial level of disability and prominent fear-avoidance behaviour, can
      be distinguished that may need additional cognitive-behavioural treatment.

PMID- 20035359
TI  - 3D postural balance with regard to gravity line: an evaluation in the transversal
      plane on 93 patients and 23 asymptomatic volunteers.
AB  - Relevance of posture assessment has been reported in case of spine disorders.
      This study explores the interest in quantifying posture using 3D reconstruction
      from biplanar X-rays in free standing position and a force plate. 93 patients
      consulting for spine disorders were divided ('3D deformity', 'sagittal imbalance'
      and 'mild deformity') and compared with 23 asymptomatic volunteers. Registration
      of the gravity line (GL) in reconstruction yielded transversal position of the
      center of acoustic meati (CAM) T1, T4, T9, L3, S1 and hip axis (HA) with regard
      to GL. Transversal position of CAM and L3 appeared as relevant parameters to
      discriminate patients from volunteers. Sagittal inclination of the axis linking
      the CAM to HA was correlated with position of the CAM to GL (r = 0.92 for
      patients). In conclusion, observing posture in 3D with regard to GL provides
      clinical relevant information. CAM-HA inclination may improve postural evaluation
      without force plate.

PMID- 20035361
TI  - Retraction and fibroplasia in a polypropylene prosthesis: experimental study in
      rats.
AB  - BACKGROUND: The treatment of hernia, independent of anatomical site and technique
      utilized, generally involves using prostheses, which may cause complications,
      despite their unarguable advantage in allowing safe reinforcement. An example of
      this is possible retraction, which causes discomfort and hernia recurrence.
      Polypropylene is still the most often used biomaterial of the great number
      available. The purpose of this study is to evaluate the amount of retraction of
      the polypropylene mesh, as well as the histological reactions that accompany this
      phenomenon. METHODS: Polypropylene meshes (Marlex) were inserted in an anterior
      position to the whole abdominal aponeurosis of 25 Wistar rats (Rattus norvegicus
      albinus). The animals were divided into groups and another intervention was
      performed 7, 28, and 90 days later to measure the dimensions of the prostheses
      and to calculate the final area. Histological analysis was performed with
      hematoxylin-eosin to evaluate neutrophils, macrophages, giant cells, and
      lymphocytes surrounding the mesh threads in ten random fields of each slide.
      RESULTS: Seven days after the mesh was inserted, the mean rate of retraction was
      1.75% (P = 0.64); at 28 days, it was 3.75% (P = 0.02); and at 90 days, it was
      2.5% (P = 0.01). As to the histological analysis, there was a total decline of
      neutrophils and a progressive increase of macrophages, giant cells, and
      lymphocytes proportional to the post-implant time of the mesh (P < 0.05).
      CONCLUSION: There was a statistically significant retraction of 3.75% at 28 days
      and 2.5% at 90 days after the prosthesis was inserted. There is a well
      established sequence of cellular events which aim at synthesizing new connective
      tissue to reinforce the mesh.

PMID- 20035360
TI  - Cadmium(II) complex formation with glutathione.
AB  - Complex formation between heavy metal ions and glutathione (GSH) is considered as
      the initial step in many detoxification processes in living organisms. In this
      study the structure and coordination between the cadmium(II) ion and GSH were
      investigated in aqueous solutions (pH 7.5 and 11.0) and in the solid state, using
      a combination of spectroscopic techniques. The similarity of the Cd K-edge and
      L(3)-edge X-ray absorption spectra of the solid compound
      [Cd(GS)(GSH)]ClO(4).3H(2)O, precipitating at pH 3.0, with the previously studied
      cysteine compound {Cd(HCys)(2).H(2)O}(2).H(3)O(+).ClO(4) (-) corresponds to Cd(S
      GS)(3)O (dominating) and Cd(S-GS)(4) four-coordination within oligomeric
      complexes with mean bond distances of 2.51 +/- 0.02 A for Cd-S and 2.24 +/- 0.04
      A for Cd-O. For cadmium(II) solutions (C (Cd(II)) approximately 0.05 M) at pH 7.5
      with moderate excess of GSH (C (GSH)/C (Cd(II)) = 3.0-5.0), a mix of Cd(S-GS)(3)O
      (dominating) and Cd(S-GS)(4) species is consistent with the broad (113)Cd NMR
      resonances in the range 632-658 ppm. In alkaline solutions (pH 11.0 and C (GSH)/C
      (Cd(II)) = 2.0 or 3.0), two distinct peaks at 322 and 674 ppm are obtained. The
      first peak indicates six-coordinated mononuclear and dinuclear complexes with
      CdS(2)N(2)(N/O)(2) and CdSN(3)O(2) coordination in fast exchange, whereas the
      second corresponds to Cd(S-GS)(4) sites. At high ligand excess the tetrathiolate
      complex, Cd(S-GS)(4), characterized by a sharp delta((113)Cd) NMR signal at 677
      ppm, predominates. The average Cd-S distance, obtained from the X-ray absorption
      spectra, varied within a narrow range, 2.49-2.53 A, for all solutions (pH 7.5 and
      11.0) regardless of the coordination geometry.

PMID- 20035362
TI  - Distal sudomotor findings in postural tachycardia syndrome.
AB  - OBJECTIVES: Postural tachycardia syndrome (POTS) is a heterogeneous disorder
      characterized by excessive orthostatic tachycardia in the absence of orthostatic
      hypotension and by sympathetic nervous system activation. Postganglionic
      sudomotor deficits have been used to define a neurogenic postural tachycardia
      POTS subtype. Norepinephrine levels above 600 pg/ml have also been used to
      delineate patients with a hyperadrenergic state. This study aims to determine the
      relationship of sudomotor abnormalities to other aspects of dysautonomia in POTS.
      METHODS: Autonomic function was quantified in thirty women through tests of
      cardiovagal, adrenergic, and sudomotor function including quantitative sudomotor
      axon reflex testing (QSART) and spectral indices. Differences between patients
      with and without sudomotor dysfunction as defined by QSART and between patients
      with and without hyperadrenergic POTS were assessed with Mann-Whitney U test and
      Mantel-Haenszel Chi-Square test using a p value of 0.01 for significance.
      Spearman correlation coefficients were used to test raw sweat volume correlations
      with other variables. RESULTS: Of 30 women (ages 20-58), 17 patients (56%) had an
      abnormal QSART which was typically patchy and involved the lower extremity, while
      13 patients had normal QSART results. Other autonomic tests, catecholamines or
      spectral indices did not correlate with QSART results. No differences in
      autonomic tests or spectral indices were observed between hyperadrenergic and non
      hyperadrenergic POTS. INTERPRETATION: Our findings confirm that a large subset of
      POTS patients have sudomotor abnormalities which are typically patchy in
      distribution but do not correlate with other tests of autonomic function. Further
      studies are needed to determine the best method of endophenotyping patients with
      POTS.

PMID- 20035363
TI  - A comparative view of insect circadian clock systems.
AB  - Recent studies revealed that the neuronal network controlling overt rhythms shows
      striking similarity in various insect orders. The pigment-dispersing factor seems
      commonly involved in regulating locomotor activity. However, there are
      considerable variations in the molecular oscillatory mechanism, and input and
      output pathways among insects. In Drosophila, autoregulatory negative feedback
      loops that consist of clock genes, such as period and timeless are believed to
      create 24-h rhythmicity. Although similar clock genes have been found in some
      insects, the behavior of their product proteins shows considerable differences
      from that of Drosophila. In other insects, mammalian-type cryptochrome (cry2)
      seems to work as a transcriptional repressor in the feedback loop. For photic
      entrainment, Drosophila type cryptochrome (cry1) plays the major role in
      Drosophila while the compound eyes are the major photoreceptor in others. Further
      comparative study will be necessary to understand how this variety of clock
      mechanisms derived from an ancestral one.

PMID- 20035364
TI  - The role of synapsins in neuronal development.
AB  - The synapsins, the first identified synaptic vesicle-specific proteins, are
      phosphorylated on multiple sites by a number of protein kinases and are involved
      in neurite outgrowth and synapse formation as well as in synaptic transmission.
      In mammals, the synapsin family consists of at least 10 isoforms encoded by 3
      distinct genes and composed by a mosaic of conserved and variable domains. The
      synapsins are highly conserved evolutionarily, and orthologues have been found in
      invertebrates and lower vertebrates. Within nerve terminals, synapsins are
      implicated in multiple interactions with presynaptic proteins and the actin
      cytoskeleton. Via these interactions, synapsins control several mechanisms
      important for neuronal homeostasis. In this review, we describe the main
      functional features of the synapsins, in relation to the complex role played by
      these phosphoproteins in neuronal development.

PMID- 20035365
TI  - Mathematical modeling of Kluyveromyces marxianus growth in solid-state
      fermentation using a packed-bed bioreactor.
AB  - This work investigated the growth of Kluyveromyces marxianus NRRL Y-7571 in solid
      state fermentation in a medium composed of sugarcane bagasse, molasses, corn
      steep liquor and soybean meal within a packed-bed bioreactor. Seven experimental
      runs were carried out to evaluate the effects of flow rate and inlet air
      temperature on the following microbial rates: cell mass production, total
      reducing sugar and oxygen consumption, carbon dioxide and ethanol production,
      metabolic heat and water generation. A mathematical model based on an artificial
      neural network was developed to predict the above-mentioned microbial rates as a
      function of the fermentation time, initial total reducing sugar concentration,
      inlet and outlet air temperatures. The results showed that the microbial rates
      were temperature dependent for the range 27-50 degrees C. The proposed model
      efficiently predicted the microbial rates, indicating that the neural network
      approach could be used to simulate the microbial growth in SSF.

PMID- 20035366
TI  - Bevacizumab-induced diffusion-restricted lesions in malignant glioma patients.
AB  - Bevacizumab is an anti-vascular endothelial growth factor (VEGF) antibody with
      activity against recurrent malignant glioma inducing high rates of objective
      responses as assessed by magnetic resonance imaging (MRI). However, the
      mechanisms of the anti-tumor action of bevacizumab are controversial. In
      particular, it is unclear whether and when bevacizumab induces hypoxia in
      gliomas. Vascular normalization with hyperperfusion and enhanced oxygen delivery
      to the tumor has been suggested as an alternative mechanism. We analyzed
      diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps in
      18 consecutive patients with recurrent malignant glioma before and after exposure
      to bevacizumab. Stroke-like lesions with diffusion restriction on DWI and
      corresponding ADC decrease were induced by bevacizumab within the previously
      enhancing tumor area in 13 of 18 patients. These lesions were detectable as early
      as 4 weeks after initiation of therapy and were maintained for up to 80 weeks. In
      one patient, an ADC-decreased lesion was biopsied, and histology showed atypical
      necrosis and nuclear hypoxia-inducible factor 1alpha upregulation but no tumor
      recurrence. Normalized regional cerebral blood flow (rCBF) and regional cerebral
      blood volume (rCBV) were analyzed in selected patients. Both parameters were
      decreased in responders with diffusion-restricted lesions. Within the tumor bed,
      bevacizumab induces diffusion-restricted lesions in the presence of reduced rCBF
      and rCBV. The cause of these alterations is unclear but may involve atypical
      necrosis and chronic hypoxia.

PMID- 20035368
TI  - High rate of deletion of chromosomes 1p and 19q in insular oligodendroglial
      tumors.
AB  - It has been reported recently that oligodendroglial tumors arising in the insula
      rarely harbor co-deletions of chromosomes 1p and 19q, a molecular signature which
      is associated with a good prognosis and increased responsiveness to radiation and
      chemotherapy compared with tumors in which 1p and/or 19q is intact. In the
      context of this claim, we analyzed a series of insular oligodendroglial tumors in
      order to determine the frequency of 1p/19q co-deletion in tumors arising in this
      region. We identified 14 insular cases operated on after 2003 in which testing
      for losses of 1p and 19q was performed. Of these cases, co-deletion of 1p and 19q
      occurred in eight (57%). Four (50%) of eight oligodendrogliomas and four (67%) of
      six oligoastrocytomas demonstrated 1p/19q co-deletions. Seven of the eight tumors
      with co-deletion of 1p/19q were WHO grade II gliomas. There were no statistical
      differences between tumors with 1p/19q co-deletion compared to those with 1p
      and/or 19q intact in terms of age, preoperative KPS, presenting symptoms, left
      versus right lateralization, tumor location (purely insular versus extension into
      frontal or temporal lobe), preoperative tumor size. There was a preponderance of
      females in the co-deletion group, and a greater average extent of resection. In
      contradistinction to previous reports, loss of 1p/19q occurs commonly in insular
      oligodendroglial tumors. With respect to 1p/19q, insular gliomas do not appear to
      be distinct from gliomas arising elsewhere in the brain.

PMID- 20035367
TI  - Overexpression of septin 7 suppresses glioma cell growth.
AB  - Our previous study demonstrated that SEPT7 was downregulated at mRNA level in
      human gliomas. This study is to further examine the expression of SEPT7 in glioma
      samples and characterizes its role on cell cycle progression and growth of glioma
      cells. mRNA and protein expression of SEPT7 were detected by RT-PCR,
      immunohistochemical staining, and western blot analysis in human glioma specimens
      and normal brain tissues. A pcDNA3-SEPT7 expression plasmid was constructed and
      transfected into human glioblastoma cell line U251, and cell proliferation and
      apoptosis were examined. The growth of established U251 and TJ905 subcutaneous
      xenograft gliomas was measured in nude mice treated with pcDNA3-SEPT7 and U251
      xenograft tumors treated with SEPT7 siRNA. SEPT7 expression is negatively
      correlated with the increase of glioma grade. Overexpression of SEPT7 is able to
      inhibit cell proliferation and arrest cell cycle progression in the G0/G1 phase
      both in vitro and in vivo. Knocking down further the already low endogenous
      expression of SEPT7 in U251 xenograft tumors with siRNA leads to faster tumor
      growth compared with control tumors. This study demonstrates that SEPT7 is
      involved in gliomagenesis and suppresses glioma cell growth.

PMID- 20035369
TI  - Purification and characterization of an anti-Prelog alcohol dehydrogenase from
      Oenococcus oeni that reduces 2-octanone to (R)-2-octanol.
AB  - An anti-Prelog alcohol dehydrogenase from Oenococcus oeni that reduces 2-octanone
      to (R)-2-octanol was purified by 26-fold to homogeneity. The enzyme had a
      homodimeric structure consisting of 49 kDa subunits, required NADPH, but not
      NADH, as a cofactor and was a Zn-independent short-chain dehydrogenase. Aliphatic
      methyl ketones (chain length > or =6 carbon atoms) and aromatic methyl ketones
      were the preferred substrates for the enzyme, the best being 2-octanone. Maximum
      enzyme activity with 2-octanone was at 45 degrees C and at pH 8.0.

PMID- 20035370
TI  - Chitinolytic and antifungal activity of a Bacillus pumilus chitinase expressed in
      Arabidopsis.
AB  - The Bacillus pumilus SG2 chitinase gene (ChiS) and its truncated form lacking
      chitin binding (ChBD) and fibronectin type III (FnIII) domains were transformed
      to Arabidopsis plants and the expression, functionality and antifungal activity
      of the recombinant proteins were investigated. Results showed that while the two
      enzyme forms showed almost equal hydrolytic activity toward colloidal chitin,
      they exhibited a significant difference in antifungal activity. Recombinant ChiS
      in plant protein extracts displayed a high inhibitory effect on spore germination
      and radial growth of hyphae in Alternaria brassicicola, Fusarium graminearum and
      Botrytis cinerea, while the activity of the truncated enzyme was strongly
      abolished. These findings demonstrate that ChBD and FnIII domains are not
      necessary for hydrolysis of colloidal chitin but play an important role in
      hydrolysis of chitin-glucan complex of fungal cell walls. Twenty microgram
      aliquots of protein extracts from ChiS transgenic lines displayed strong
      antifungal activity causing up to 80% decrease in fungal spore germination. This
      is the first report of a Bacillus pumilus chitinase expressed in plant system.

PMID- 20035371
TI  - Human dermal fibroblast proliferation activity of usimine-C from Antarctic lichen
      Ramalina terebrata.
AB  - Type I collagen is the major structural protein in dermis and its presence is
      used to monitor skin cell proliferation and aging. Recently, novel usimine
      compounds have been found in the Antarctic lichen Ramalina terebrata. In the
      present study, usimine-C induced cell proliferation of human dermal fibroblast,
      CCD-986SK, up to 1.6-fold after treating with 90 microg/ml for 48 h. Type I
      procollagen synthesis was significantly increased 1.3-fold, 3-fold, and 5-fold
      after treating with 0.14, 0.72, and 3.6 microg usimine-C/ml for 24 h,
      respectively, whereas no significant increase in type I procollagen was observed
      after treating with usimine-A or -B. Usimines are usnic acid derivatives.
      Considering that the difference among the derivatives is a side chain, the
      proliferation activity may be related to this side chain, triggering an internal
      signal for type I procollagen expression. Further studies still remain to clarify
      the signaling pathways for the type I procollagen induction, which is activated
      by usimine-C.

PMID- 20035372
TI  - Controlling the adhesion of the diatom Navicula perminuta using poly(N
      isopropylacrylamide-co-N-(1-phenylethyl) acrylamide) films.
AB  - Poly(N-isopropylacrylamide)-co-N-(1-phenylethyl) acrylamide [P(NIPAAm-co-PEAAm)]
      thermo-responsive thin films with a lower critical solution temperature (LCST)
      adjusted to fit marine applications were used to investigate the effect of
      changes in the wetting properties of a surface on the adhesion of the diatom
      Navicula perminuta, an organism which forms slime films on surfaces immersed in
      an aquatic environment. Although the strength of attachment of cells was affected
      by whether the film was collapsed or expanded, no significant decrease in
      adhesion strength occurred upon temperature decrease. The effects were attributed
      to possible strong interactions between the hydrophobic segments of the
      responsive film when collapsed with components in the adhesive complex.

PMID- 20035373
TI  - Surface spectroscopy of adsorbed proteins: input of data treatment by principal
      component analysis.
AB  - X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass
      spectroscopy (ToF-SIMS), two surface-sensitive spectroscopic methods, are
      commonly used to characterize adsorbed protein layers. Principal component
      analysis (PCA) is a statistical method which aims at reducing the number of
      variables in complex sets of data while retaining most of the original
      information. The aim of this paper is to review work carried out in our group
      regarding the use of PCA with a view to facilitate and deepen the interpretation
      of ToF-SIMS or XPS spectra acquired on adsorbed protein layers. ToF-SIMS data
      acquired on polycarbonate membranes after albumin and, or insulin adsorption were
      treated with PCA. The results reveal the preferential exposure of particular
      amino acids at the outermost surface depending on the adsorption conditions
      (nature of the substrate and of the proteins involved, concentration in
      solution), giving insight into the adsorption mechanisms. PCA was applied on XPS
      data collected on three different substrates after albumin or fibrinogen
      adsorption, followed in some cases by a cleaning procedure with oxidizing agents.
      The results allow samples to be classified according to the nature of the
      substrate and to the adsorbed amount and, or the level of surface coverage by the
      protein. Chemical shifts of particular interest are also identified, which may
      facilitate further peak decomposition. It is useful to recall that the outcome of
      PCA strongly depends on data selection and normalisation.

PMID- 20035374
TI  - Candida albicans enhances experimental hepatic melanoma metastasis.
AB  - Candida albicans infections are very frequent in cancer patients, whose immune
      system is often compromised, but whether this fungal pathogen affects cancer
      progression is unknown. C. albicans infection involves endogenous production of
      inflammatory cytokines such as tumour necrosis factor alpha (TNF-alpha) and
      interleukin-18 (IL-18). Increased levels of these cytokines have already been
      correlated with metastasis of most common cancer types. In this study, a well
      established model of IL-18-dependent hepatic melanoma metastasis was used to
      study whether C. albicans can alter the ability of murine B16 melanoma (B16M)
      cells to colonize the liver. First, we determined the ability of intrasplenically
      (IS) injected B16M cells to metastasize into the liver of mice challenged with 5
      x 10(4) C. albicans cells by three different routes (intravenous, IV;
      intrasplenic, IS; or intraperitoneal, IP) 12 h prior to injection of B16M cells.
      We demonstrated that C. albicans significantly increased metastasis of B16M cells
      with all three fungal injection routes. Pro-metastatic effects occurred when
      hepatic colonization with B16M cells place after the peak of TNF-alpha and IL-18
      levels had been reached in the hepatic blood of fungal challenged mice. In a
      second set of experiments, mice were fungal challenged 4 days after injection of
      B16M cells. In these mice, C. albicans also potentiated the growth of established
      micro-metastases. Significantly, the fungal challenge had pro-metastatic effects
      without the C. albicans being able to reach the liver, suggesting that soluble
      factors can promote metastasis in remote sites. Mouse treatment with antifungal
      ketoconazol abrogated hepatic TNF-alpha stimulation by C. albicans and prevented
      the enhancement of hepatic metastasis in fungal challenged-mice. Therefore, the
      pro-inflammatory microenvironment generated by the host's systemic response to C.
      albicans stimulates circulating cancer cells to metastasize in the liver.

PMID- 20035375
TI  - Accelerated blood clearance was not induced for a gadolinium-containing PEG
      poly(L-lysine)-based polymeric micelle in mice.
AB  - PURPOSE: Accelerated blood clearance (ABC) is induced by repeated injections of
      PEGylated liposomes. In this study, the ABC was investigated for a gadolinium
      containing PEG-poly(L-lysine)-based polymeric micelle (Gd-micelle) and PEGylated
      liposome (Gd-liposome) in mice. MATERIALS AND METHODS: Effects of the first
      injection of Gd-micelle on the tissue distribution of the second dose of Gd
      micelle were studied. Additionally, effects of the first injection of Gd-micelle,
      Gd-liposome, empty liposome, polyethyleneglycol (PEG(500,000)), and PEG-lipid on
      the distribution of the second dose of the Gd-liposome were evaluated. RESULTS:
      Results indicated that the tissue distribution of the second injection of the Gd
      micelle at a dose of 33, 5, or 2 micromol Gd/kg was not affected by the first
      injection of the Gd-micelle at different doses and time intervals or of the empty
      PEGylated liposome 7 days before. ABC of Gd-liposome at a dose of 2.3 micromol
      Gd/kg (corresponding to 10 micromol lipids/kg) was observed when the empty
      PEGylated liposome or Gd-liposome, but not the Gd-micelle, PEG(500,000) or PEG
      lipid, was pre-administered. CONCLUSIONS: The hydrophobic core of the micelle or
      lipid bilayer of PEGylated liposome has a major effect on this phenomenon. These
      studies have significant implications for the evaluation of PEG-poly(L-lysine)
      based micellar formulation of Gd-based contrast agents.

PMID- 20035376
TI  - Putative recombination events and evolutionary history of five economically
      important viruses of fruit trees based on coat protein-encoding gene sequence
      analysis.
AB  - To enhance the knowledge of recombination as an evolutionary process, 267
      accessions retrieved from GenBank were investigated, all belonging to five
      economically important viruses infecting fruit crops (Plum pox, Apple chlorotic
      leaf spot, Apple mosaic, Prune dwarf, and Prunus necrotic ringspot viruses).
      Putative recombinational events were detected in the coat protein (CP)-encoding
      gene using RECCO and RDP version 3.31beta algorithms. Based on RECCO results, all
      five viruses were shown to contain potential recombination signals in the CP
      gene. Reconstructed trees with modified topologies were proposed. Furthermore,
      RECCO performed better than the RDP package in detecting recombination events and
      exhibiting their evolution rate along the sequences of the five viruses. RDP,
      however, provided the possible major and minor parents of the recombinants. Thus,
      the two methods should be considered complementary.

PMID- 20035378
TI  - TNFalpha -308 G/A polymorphism is associated with breast cancer risk: a meta
      analysis involving 10,184 cases and 12,911 controls.
AB  - Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine which can
      regulate a wide variety of cellular responses. Low concentrations of TNFalpha
      seem to increase tumor growth and progression. The -308 G/A polymorphism in
      TNFalpha has been implicated in breast cancer risk but the published data remain
      inconclusive. In order to derive a more precise estimation of the relationship, a
      meta-analysis was performed by searching PubMed, Web of Science, ScienceDirect,
      EBSCO, CNKI, and Chinese Biomedicine Database. 11 studies including 10,184 cases
      and 12,911 controls were collected for TNFalpha -308 G/A polymorphism. Crude ORs
      with 95% CIs were used to assess the strength of association between the TNFalpha
      -308 G/A polymorphism and breast cancer risk. The pooled ORs were performed for
      codominant model (GG versus AA; GA versus AA), dominant model (GG + GA versus
      AA), recessive model (GG versus GA + AA), and G allele versus A allele,
      respectively. Overall, significantly elevated breast cancer risk was found for
      recessive model (OR = 1.10, 95% CI = 1.04-1.17) and for G allele versus A allele
      (OR = 1.08, 95% CI = 1.02-1.14). In the subgroup analysis by ethnicity,
      significantly increased risks were also found among Caucasians for recessive
      model and for G allele versus A allele (for recessive model: OR = 1.10, 95% CI =
      1.04-1.17; for G allele versus A allele: OR = 1.09, 95% CI = 1.03-1.14). However,
      no significant associations were found among Asians for all genetic models. In
      conclusion, this meta-analysis suggests that the TNFalpha -308 G allele is a risk
      factor for developing breast cancer, especially for Caucasians.

PMID- 20035377
TI  - Mesotrypsin promotes malignant growth of breast cancer cells through shedding of
      CD109.
AB  - Serine proteases have been implicated in many stages of cancer development,
      facilitating tumor cell growth, invasion, and metastasis, and naturally occurring
      serine protease inhibitors have shown promise as potential anticancer
      therapeutics. Optimal design of inhibitors as potential therapeutics requires the
      identification of the specific serine proteases involved in disease progression
      and the functional targets responsible for the tumor-promoting properties. Here,
      we use the HMT-3522 breast cancer progression series grown in 3D organotypic
      culture conditions to find that serine protease inhibitors cause morphological
      reversion of the malignant T4-2 cells, assessed by inhibition of proliferation
      and formation of acinar structures with polarization of basal markers,
      implicating serine protease activity in their malignant growth behavior. We
      identify PRSS3/mesotrypsin upregulation in T4-2 cells as compared to their
      nonmalignant progenitors, and show that knockdown of PRSS3 attenuates, and
      treatment with recombinant purified mesotrypsin enhances, the malignant growth
      phenotype. Using proteomic methods, we identify CD109 as the functional
      proteolytic target of mesotrypsin. Our study identifies a new mediator and
      effector of breast cancer growth and progression.

PMID- 20035379
TI  - Tamoxifen sensitivity and estrogen receptor mRNA levels.

PMID- 20035380
TI  - Four polymorphisms in cytochrome P450 1A1 (CYP1A1) gene and breast cancer risk: a
      meta-analysis.
AB  - Cytochrome P450s are enzymes which catalyze Phase-I metabolism reactions;
      cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family and participates in
      the metabolism of a vast number of xenobiotics, as well as endogenous substrates.
      Four single nucleotide polymorphisms in CYP1A1 have been studied concerning their
      potential implication in terms of breast cancer risk: T3801C, T3205C, A2455G
      (Ile462Val), and C2453A (Thr461Asp); controversy exists regarding their role.
      This meta-analysis aims to examine whether the four aforementioned polymorphisms
      are associated with breast cancer risk. Separate analyses were performed on
      Caucasian, Chinese, and African populations, as well as on premenopausal and
      postmenopausal women. Eligible articles were identified by a search of MEDLINE
      bibliographical database for the period up to October 2009. Concerning T3801C, 32
      studies were eligible (11,909 cases and 16,179 controls), 29 studies (12,257
      cases and 20,379 controls) were eligible for A2455G, 11 studies (7,189 cases and
      8,491 controls) were eligible for C2453A, and eight studies were eligible for
      T3205C (1,378 cases and 1,642 controls). Pooled odds ratios (OR) were
      appropriately derived from fixed- or random-effect models. Sensitivity analysis
      excluding studies whose genotype frequencies in controls significantly deviated
      from Hardy-Weinberg equilibrium was performed. Homozygous subjects of Caucasian
      origin carrying the A2455G G allele exhibited elevated breast cancer risk (pooled
      OR = 2.185, 95% CI 1.253-3.808, fixed effects), whereas heterozygous carriers did
      not (pooled OR = 1.062, 95% CI 0.852-1.323, random effects). A2455G polymorphism
      status was not associated with breast cancer risk in Chinese subjects or
      specifically in premenopausal/postmenopausal women. T3801C, T3205C, and C2453A
      status were not associated with breast cancer risk at any analysis. In
      conclusion, this meta-analysis points to the A2455G G allele as a risk factor for
      breast cancer among Caucasian subjects. On the contrary, T3801C, T3205C, and
      C2453A status does not seem capable of modifying breast cancer risk.

PMID- 20035381
TI  - Effect of a switch of aromatase inhibitors on musculoskeletal symptoms in
      postmenopausal women with hormone-receptor-positive breast cancer: the ATOLL
      (articular tolerance of letrozole) study.
AB  - The objective of the present study was to evaluate the effect of the switch of
      aromatase inhibitors (AIs) on musculoskeletal symptoms in postmenopausal women
      with hormone-receptor-positive breast cancer. This was a 6-month, prospective,
      non-randomized, multicenter study. Patients who had discontinued anastrozole due
      to musculoskeletal symptoms were eligible to participate in this study, and
      received letrozole, which was initiated 1 month after anastrozole
      discontinuation. Musculoskeletal symptoms were systematically assessed for
      severity, location of the symptoms, presence of swelling and of morning stiffness
      by the oncologist patients when patients stopped taking their anastrozole, 1
      month after the discontinuation of anastrozole, and 1, 3, and 6 months after
      initiating the letrozole therapy. The primary endpoint was the percentage of
      patients who discontinued letrozole due to the severe musculoskeletal symptoms.
      After switching from anastrozole therapy, and at the end of the 6-month letrozole
      treatment, 128 (71.5%) out of 179 patients (61.3 +/- 8.4 years) continued with
      letrozole. Fifty-one patients (28.5%) discontinued treatment due to severe joint
      pain. At the end of the 6-month, 116 patients (73.9%) had arthralgia, 33 (21.0%)
      myalgia, 25 (15.9%) arthritis, 22 (14.0%) tendinitis, and 20 (12.7%) polyalgic
      syndrome. Bivariate analysis of the factors associated with letrozole
      discontinuation showed that the duration of a prior anastrozole treatment was a
      significant predictor (P = 0.04). This study shows that in patients intolerant to
      one AI, switching to another agent allows a higher proportion of patients to
      continue the therapy and maximize hormonal adjuvant therapy and disease outcome
      benefits.

PMID- 20035383
TI  - In vivo neuroprotective effects of peripheral kynurenine on acute neurotoxicity
      induced by glutamate in rat cerebral cortex.
AB  - N-methyl-D-aspartate (NMDA) receptors play a crucial role in Glutamate (L-Glu)
      neurotoxicity. To evaluate the effects of astrocyte-derived tryptophan metabolite
      kynurenic acid (KYNA), on L-Glu neurotoxicity, adult male rats were pretreated
      with Kynurenine (KYN) which is a precursor of KYNA, at a dose of 30 mg or 300
      mg/kg bw i.p., 2 h before stereotactic L-Glu bolus (1 micromole/1 microl)
      administration in cerebral cortex. Results showed that acute L-Glu increased
      reactive oxygen species, rate of lipid peroxidation, calcium, nitric oxide and
      neuroinflammatory markers viz. TNF-alpha, IFN-gamma levels and decreased key
      antioxidant parameters such as SOD, catalase, total glutathione and glutathione
      reductase along with mitochondrial membrane potential. While peripheral loading
      of 30 mg/kg dose of KYN had no protective effects on L-Glu induced neurotoxicity,
      300 mg/kg dose prevented the above toxic effects following intracortical L-Glu.
      KYN apparently crossed blood brain barrier to elevate astrocytic-KYNA level,
      which seems to protect neurons through several interactive mechanisms.

PMID- 20035384
TI  - Housing model for persons with serious mental illness moderates the relation
      between loneliness and quality of life.
AB  - This study compared levels of loneliness, quality of life (QOL) and social
      support among people with serious mental illness (SMI) living in two different
      types of housing: group homes and supportive community housing. Forty persons
      with SMI living in supportive community housing and 57 living in a group home
      completed measures of QOL, symptoms, perceived social support and loneliness.
      Analysis of variance tests were conducted to examine whether there were
      differences in degree of loneliness, QOL and social support between the groups
      living in the two residential types. No significant differences between the two
      housing models were found. Correlational analysis, however, indicated a strong
      relationship between loneliness and QOL. Subsequent regression analysis revealed
      that residence in group homes moderates the relationship between social
      loneliness and QOL, such that social loneliness impacted QOL only among group
      home residence. Implications of the findings for understanding the impact of
      housing on QOL are discussed.

PMID- 20035382
TI  - Novel methodologies in marine fish larval nutrition.
AB  - Major gaps in knowledge on fish larval nutritional requirements still remain.
      Small larval size, and difficulties in acceptance of inert microdiets, makes
      progress slow and cumbersome. This lack of knowledge in fish larval nutritional
      requirements is one of the causes of high mortalities and quality problems
      commonly observed in marine larviculture. In recent years, several novel
      methodologies have contributed to significant progress in fish larval nutrition.
      Others are emerging and are likely to bring further insight into larval
      nutritional physiology and requirements. This paper reviews a range of new tools
      and some examples of their present use, as well as potential future applications
      in the study of fish larvae nutrition. Tube-feeding and incorporation into
      Artemia of (14)C-amino acids and lipids allowed studying Artemia intake,
      digestion and absorption and utilisation of these nutrients. Diet selection by
      fish larvae has been studied with diets containing different natural stable
      isotope signatures or diets where different rare metal oxides were added.
      Mechanistic modelling has been used as a tool to integrate existing knowledge and
      reveal gaps, and also to better understand results obtained in tracer studies.
      Population genomics may assist in assessing genotype effects on nutritional
      requirements, by using progeny testing in fish reared in the same tanks, and also
      in identifying QTLs for larval stages. Functional genomics and proteomics enable
      the study of gene and protein expression under various dietary conditions, and
      thereby identify the metabolic pathways which are affected by a given nutrient.
      Promising results were obtained using the metabolic programming concept in early
      life to facilitate utilisation of certain nutrients at later stages. All
      together, these methodologies have made decisive contributions, and are expected
      to do even more in the near future, to build a knowledge basis for development of
      optimised diets and feeding regimes for different species of larval fish.

PMID- 20035385
TI  - Pulmonary toxicity in patients receiving docetaxel chemotherapy.
AB  - Pulmonary toxicity can rarely be seen with cytotoxic agents. We aimed at
      investigating the pulmonary toxicity of docetaxel in patients other than lung
      carcinoma. Forty patients were investigated prospectively. Spirometry, DLCO and
      high-resolution computed tomography (HRCT) scans were applied to all patients
      before and 14-21 days after completion of docetaxel. We used a HRCT scoring
      system that was based on the previous studies. We have seen no pulmonary symptoms
      that may reflect pulmonary toxicity. There were statistically significant
      differences between pre- and post-treatment values of FEV1 (L/s), FEV1/FVC (%),
      DLCO/VA (DLCO/L), DLCO/VA (%) (P<0.05), FEF25-75 (L/s), FEF25-75 (%) (P<0.01),
      DLCO (mL/mmHg/min), DLCO (%) (P<0.001), Also, there was a statistically
      significant difference between the pre- and post-treatment HRCT scores. There was
      a statistical relationship between post-treatment HRCT scores, number of
      docetaxel cycles (r=0.49, P<0.0001) and docetaxel cumulative dose (r=0.61,
      P<0.0001). Docetaxel caused a significant decline in pulmonary function tests
      (PFTs) and progression in HRCT scores but the symptoms of patients were not
      consistent with these differences. The negative effects of docetaxel on PFTs and
      HRCT scores should be investigated more reliably by increasing the number of
      patients with further studies.

PMID- 20035386
TI  - An unusual presentation of extramedullary plasmacytoma in testis and review of
      the literature.
AB  - Extramedullary plasmacytoma is a rare plasma cell neoplasm, and it is extremely
      uncommon in the testicles. We report a 73-year-old man with multiple myeloma
      presented with testicular plasmacytoma. He complained of left leg pain and
      scrotal swelling. Ultrasonography revealed testicular masses. Pathologic
      examination of the orchiectomy specimen showed plasmocytoma with kappa
      expression. Multiple lytic bone lesions were seen in bone survey scans, serum
      immunoelectrophoresis and bone marrow aspiration aided to the diagnosis of
      multiple myeloma. He received chemotherapy, melphalan and prednisolone, and
      palliative radiotherapy. He succumbed to disease after 8 months.

PMID- 20035387
TI  - Treatment of newly diagnosed multiple myeloma: advances in current therapy.
AB  - The past decade has seen incredible progress in the treatment of myeloma as a
      result of more widespread application of autologous stem cell transplantation and
      introduction of several new drugs. Hence, the survival of patients with this
      disease has significantly improved during this period. The treatment approach for
      patients with myeloma has undergone a paradigm shift as a result of the different
      choices available for treating the patients with newly diagnosed myeloma. In
      addition, appreciation of the heterogeneity in the outcome of these patients and
      the impact of genetics on the prognosis has led to efforts at developing a risk
      adapted approach to treatment. This article summarizes the recent advances in the
      treatment of newly diagnosed myeloma and suggests a treatment algorithm for
      approaching newly diagnosed myeloma.

PMID- 20035388
TI  - The validity of multi-center common normal database for identifying myocardial
      ischemia: Japanese Society of Nuclear Medicine working group database.
AB  - PURPOSE: The Japanese Society of Nuclear Medicine (JSNM) working group has
      created a myocardial perfusion imaging database applicable to standard
      acquisition protocol. The aim of this study is to validate the diagnostic
      accuracy of the common normal database compared with the expert interpretation of
      each institute. METHODS: Five institutions participated in this study and used
      different acquisition settings which included 360 degrees /180 degrees rotation,
      camera configuration and camera orbits. The software and its version used in each
      institution also varied. The working group database was applied to detect the
      culprit coronary territory from a total of 166 patients with coronary artery
      disease (CAD) and 145 patients with low-likelihood of CAD. RESULTS: When summed
      stress score > or =4 was defined as significant abnormality, overall sensitivity,
      specificity and accuracy of patient-based analysis were 77, 72 and 75%,
      respectively, based on quantitative analysis using the common database, whereas
      those by institutional visual expert reading were 72, 79 and 75%, respectively.
      CONCLUSION: The common database, which was created by a multi-center working
      group and separated between male/female with 180/360 degrees acquisitions,
      demonstrated comparable diagnostic accuracy to expert interpretation by each
      institute, and it may be applicable to multi-center studies.

PMID- 20035389
TI  - Supine acceptance of a conventional imaging position may make you less prone to
      success.

PMID- 20035390
TI  - Interassay reproducibility of myocardial perfusion gated SPECT in patients with
      atrial fibrillation.
AB  - AIM: The aim of this study was to assess interassay reproducibility of myocardial
      perfusion gated-SPECT for calculation of end-diastolic volume (EDV), end-systolic
      volume (ESV), and left ventricular ejection fraction (LVEF) in patients with
      atrial fibrillation (AF). METHODS: One hundred and fifteen consecutive patients
      with AF from three participating hospitals (mean age 68.9 years, 39 women) were
      included in the study. All patients underwent two image gated acquisitions at
      rest with a 30 minute interval between them. Quantitative data were obtained
      using the QGS and ECT software algorithms. RESULTS: Heart rate was similar in
      both studies: 74.94 +/- 15.2 vs 73.03 +/- 15.57. QGS yielded an LVEF of
      54.4%/53.8%, an EDV of 100 mL/101.5 mL, and an ESV of 51 mL/52.3 mL; and ECT
      showed an LVEF of 63.6%/62.9%, an EDV of 125.8 mL/127.4 mL and ESV of 54.1
      mL/56.3 mL. Correlation between the two acquisitions was high (>0.948) for both
      methods for LVEF, EDV and ESV. Regression and Bland-Altman graphics showed a good
      agreement between all parameters. Interassay variation coefficients for each
      method (QGS/ECT) were 5.29% vs 4.83% for LVEF, 4.94% vs 5.17% for EDV, and 9.94%
      vs 12.78% for ESV. CONCLUSIONS: Interassay reproducibility of LVEF and EDV with
      gated-SPECT in patients with AF is good, whereas for ESV it is suboptimal,
      particularly when ESV is small.

PMID- 20035391
TI  - Transient ischemic dilatation ratio derived from myocardial perfusion
      scintigraphy: What are we looking at?
AB  - BACKGROUND: Elevated transient ischemic dilatation (TID) ratio during myocardial
      perfusion imaging (MPI) is described as a marker of severe CAD, even in
      acquisitions with normal perfusion. This was initiated to explore the effects of
      stressor type on the TID. Additionally the relation between the TID and other
      functional parameters, such as end diastolic volume (EDV), end systolic volume
      (ESV), and left ventricle ejection fraction (LVEF), heart rate (HR), and severity
      of ischemia, was evaluated. METHOD: A total of 299 consecutive patients referred
      for a 2-day stress/rest MPI protocol were included. Patients were stressed with
      either adenosine (n = 164) or exercise (n = 135). MPI data were analyzed with an
      automated software tool to determine TID, EDV, ESV, LVEF, SSS, and SDS. The SDS
      was used to quantify the degree of ischemia, with a SDS > or = 3 considered
      ischemic. RESULTS: Comparison of the adenosine and exercise stressed population
      revealed significant differences, especially in parameters derived from the
      poststress acquisition. Within the exercise stressed population, TID was
      proportional with the SDS (R(2) = .12); whereas the adenosine population did not
      show such a relation (R(2) = .001). Difference in HR between rest and poststress
      acquisitions showed high levels of linear regression with TID values of both the
      adenosine (R(2) = .41) and exercise (R(2) = .29) stressed population. CONCLUSION:
      In an exercise stressed population, TID is determined by both the degree of
      ischemia and the heart-rate difference between the two acquisition moments. TID
      within the adenosine population was found to be highly proportional with the HR,
      rather than with the degree of ischemia.

PMID- 20035392
TI  - Eosin-shadow method: a selective enhancement of light-microscopic visualization
      of pancreatic zymogen granules on hematoxylin-eosin sections.
AB  - We developed a novel method for enhancing light-microscopic visualization of
      pancreatic zymogen granules in a selective manner on hematoxylin and eosin
      stained sections. By using an absorption filter that transmits light with
      wavelength from 510 to 550 nm, corresponding to the narrow absorption spectrum of
      eosin, only eosinophilic tissue and cellular components were remarkably
      highlighted as distinct shadows against lighter background consisting of
      basophilic components. Using a pair of mirror sections of the pancreas,
      immunocytochemistry with anti-amylase antibody confirmed that the shadows
      observed through the filter represented zymogen granules. Immersion in formalin
      for 36 h at room temperature was the optimal fixation condition. Here we
      designate the procedure as the "eosin-shadow method" and propose that this
      technique is convenient and useful to help investigators identify zymogen
      granules more easily in routine pathological examination and histological
      studies.

PMID- 20035394
TI  - Safety, efficacy, and quality control of a photoelectric dye-based retinal
      prosthesis (Okayama University-type retinal prosthesis) as a medical device.
AB  - Patients with retinitis pigmentosa lose photoreceptor cells as a result of
      genetic abnormalities and hence become blind. Neurons such as bipolar cells and
      ganglion cells remain alive even in the retina of these patients, and ganglion
      cells send axons to the brain as the optic nerve. The basic concept of retinal
      prostheses is to replace dead photoreceptor cells with artificial devices to
      stimulate the remaining neurons with electric currents or potentials. Photodiode
      arrays and digital camera-type electrode arrays are the two main approaches for
      retinal prostheses to stimulate retinal neurons, but these arrays have the
      problems of poor biocompatibility, low sensitivity, and low output of electric
      currents, and hence have a requirement for external electric sources (batteries).
      To overcome these problems, we are developing photoelectric dye-based retinal
      prostheses that absorb light and convert photon energy to generate electric
      potentials. The prototype, using a photoelectric dye-coupled polyethylene film,
      could induce intracellular calcium elevation in photoreceptor-lacking embryonic
      retinal tissues and cultured retinal neurons. The subretinal implantation of the
      prototype in the eyes of Royal College of Surgeons (RCS) rats led to vision
      recovery as proved by a behavior test. The photoelectric dye that was chosen for
      the prototype did not exhibit any cytotoxicity. The surface potentials of the
      photoelectric dye-coupled film showed a rapid on-and-off response to illumination
      with a threshold for light intensity as measured by a Kelvin probe system.
      Photoelectric dye-based retinal prostheses are thin and soft, and therefore, a
      sheet of the film of large size, corresponding to a large visual field, could be
      inserted into the vitreous and then to the subretinal space through a small
      opening by rolling up the film. Clinical studies of photoelectric dye-based
      retinal prostheses in patients with retinitis pigmentosa who lose sight will be
      planned after the manufacturing control and the quality control had been
      established for the medical device.

PMID- 20035395
TI  - Impact of non-di-(2-ethylhexyl)phthalate cardiopulmonary bypass tubes on
      inflammatory cytokines and coagulation-fibrinolysis systems during
      cardiopulmonary bypass.
AB  - Di-(2-ethylhexyl)phthalate (DEHP), an excellent plasticizer for poly(vinyl
      chloride) (PVC), is a known endocrine-disrupting chemical. This study was
      designed to investigate whether a new non-DEHP bilayer tube reduced the release
      of DEHP, suppressed inflammatory cytokines, and altered coagulation-fibrinolysis
      systems. Sixteen patients undergoing coronary artery bypass grafting (CABG) were
      randomly assigned to the non-DEHP bilayer group (group B, n = 8), or the
      noncoated PVC group (group N, n = 8). The level of DEHP in the blood was measured
      before and after cardiopulmonary bypass (CPB). The levels of interleukin-6 (IL
      6), D-dimer, and thrombin-antithrombin complex (TAT) were also measured at six
      points during and after CPB. DEHP was significantly lower in group B (472 +/- 141
      ng/ml) after CPB compared with group N (2094 +/- 1046 ng/ml). The IL-6 level was
      significantly lower in group B (151 +/- 131 pg/ml) than group N (206 +/- 224
      pg/ml) 180 min after protamine administration. The D-dimer level was
      significantly lower in group B 60 min after protamine administration (6.2 +/- 2.4
      microg/ml in group B vs 10.4 +/- 4.5 microg/ml in group N) and 180 min after
      protamine administration (4.4 +/- 0.7 microg/ml in group B vs 7.3 +/- 2.7
      microg/ml in group N). Group B had a tendency toward reduced postoperative
      bleeding compared with group N at any time. The bilayer tube was superior to the
      noncoated tube in terms of the inhibition of DEHP release, inflammatory
      cytokines, and the fibrinolysis system.

PMID- 20035396
TI  - New automated wavelet analytical system with a cellular phone for recording
      intercellular phone remote transmitted bileaflet valve sound.
AB  - The wavelet analytical system developed in our institute can detect a
      malfunctioning bileaflet valve by analyzing the split interval (SI) of bileaflet
      valve sound (BLVS) caused by asynchronous closure of both leaflets. However, this
      system is limited in its clinical application because of the complications of
      both valve sound recording and analytical protocols. This study established a new
      system that improved upon these limitations, and evaluated its clinical
      efficiency and the possibility of intercellular phone remote transmission of BLVS
      (ICTB). Fifty-one valves in 36 patients with St. Jude Medical bileaflet valve
      replacement were examined by fluoroscopy, 90 BLVS files (42 mitral and 48 aortic
      valve files) were recorded, and 1720 individual BLVS recordings in these files
      were analyzed with the new system. The new system consists of a cellular phone
      for BLVS recording and an automated algorithm for analysis with the Morlet
      continuous wavelet transform. ICTB was also investigated clinically. The new
      system showed great improvement over the original system by simplifying BLVS
      recording and reducing analysis time by approximately 65%. This system detected
      two malfunctioning valves with coefficients of variation (CV) for SI below 0.112,
      a previously proposed criterion for malfunction. ICTB also proved to be a useful
      BLVS recording method for determining SI. The new system described in this study
      could eliminate the factors limiting clinical application of the old system, and
      ICTB was found to be a clinically applicable BLVS recording method.

PMID- 20035397
TI  - Effects of genistein on secretion of extracellular matrix components and
      transforming growth factor beta in high-glucose-cultured rat mesangial cells.
AB  - The ideal treatment for diabetic nephropathy should slow the progress of renal
      failure, delay the initiation of dialysis, and protect residual renal function in
      patients receiving dialysis. Renal mesangial cells play an important role in
      these processes. In the current study, we investigated the effects of genistein
      on rodent renal mesangial cells cultured in a high-glucose environment. Since
      overexpression of the extracellular matrix (ECM) components (type IV collagen and
      fibronectin) and transforming growth factor beta (TGF-beta) have been previously
      implicated in the development of the renal glomerulus damage of diabetic
      nephropathy, we included these substances in our study. The results showed that
      high concentration of glucose (450 mg.dl(-1)) stimulated the synthesis of type IV
      collagen and fibronectin and the secretion of TGF-beta. These responses were
      attenuated by genistein (> or =5 micromol.l(-1)) in a dose- and time-dependent
      manner. In conclusion, we demonstrated that genistein could inhibit the secretion
      of ECM components and the expression of TGF-beta at both the protein and mRNA
      levels. These findings should be followed up by further studies and clinical
      trials to verify the potential therapeutic effects of genistein on diabetic
      nephropathy.

PMID- 20035399
TI  - Cardiac troponins: outcome predictors in hemodialysis patients.
AB  - Cardiovascular diseases represent the main cause of death in hemodialysis (HD)
      patients. Cardiac troponins (cTnT and cTnI) are indicators of myocardial damage.
      The aims of this study were to assess the prevalence of increased serum cTn in
      the absence of acute coronary syndrome, to determine overall and cardiovascular
      mortality rates, and to investigate the possible predictive values of cTnT and
      cTnI on the outcome in HD patients over a 2-year follow-up period. The study
      included 115 patients (71 men and 44 women) with an average age of 53.30 +/-
      12.17 years who had undergone regular HD for 4.51 +/- 4.01 years and had a mean
      HD adequacy (Kt/Vsp) of 1.17 +/- 0.23. Increased serum cTnT concentration was
      found in 37.39% of patients and elevated serum cTnI concentration was present in
      11.30% of HD patients without symptoms or signs of acute coronary syndrome. The
      average 2-year mortality rate was 13.74% and the average 2-year cardiovascular
      mortality rate was 8.51%. Patients with serum cTnT levels greater than 0.10 ng/ml
      had significantly lower overall and cardiovascular survival rates than patients
      with serum cTnT levels of less than 0.10 ng/ml. Patients with serum cTnI levels
      greater than 0.15 ng/ml had significantly lower overall and cardiovascular
      survival rates than patients with serum cTnI of less than 0.15 ng/ml. In patients
      on regular HD, cTn levels are significant outcome predictors.

PMID- 20035398
TI  - Imaging glucose metabolism in perfluorocarbon-perfused hepatocyte bioreactors
      using positron emission tomography.
AB  - In vitro hepatocyte bioreactor functionality depends particularly on maintaining
      appropriate oxygen levels and exposure to nonparenchymal cells. An attractive
      solution without immunological consequences to the patient is incorporating a
      perfluorocarbon oxygen carrier in the circulating medium and co-culturing
      hepatocytes with stellate cells. Since bioreactors are normally sealed sterile
      units, demonstrating metabolic functionality is hindered by limited access to the
      cells after their aggregation in the matrix. A novel possibility is to use
      positron emission tomography (PET) to image cellular radioactive glucose uptake
      under O(2)-limited conditions. In this study, primary cell isolation procedures
      were carried out on eight pigs. Pairs of cell-seeded and cell-free (control)
      bioreactors with and without perfluorocarbon were cultured under identical
      conditions and were oxygenated using hypoxic (5% O(2)) and ambient (20% O(2)) gas
      mixes. Sixteen PET scans were conducted 24 h after cell isolation, the same
      timescale as that involved in treating a liver failure patient with a primary
      cell bioreactor. In all cases, cell-seeded bioreactors without perfluorocarbon
      were more radioactive, i.e., were more glycolytic, than those with
      perfluorocarbon. This difference was significant in the hypoxic pair of
      bioreactors but not in the ambient pair of bioreactors. Additionally, in the same
      hypoxic bioreactors, circulating extracellular steady-state glucose levels were
      significantly lower and lactate levels were higher than those in the ambient
      bioreactors. Similar findings have been made in other in vitro hepatocyte studies
      investigating the effects of perfluorocarbons. PET is attractive for studying in
      situ O(2)-dependent bioreactor metabolism because of its visual and numerically
      quantifiable outputs. Longer-term metabolic studies (e.g., 5-10 days)
      investigating the effect of perfluorocarbon on bioreactor longevity will
      complement these findings in the future.

PMID- 20035400
TI  - Development of an enzyme-free glucose sensor using the gate effect of a
      molecularly imprinted polymer.
AB  - The instability of enzymatic glucose sensors has prevented the development of a
      practical artificial pancreas for diabetic patients. We therefore developed an
      enzyme-free glucose sensor using the gate effect of a molecularly imprinted
      polymer (MIP). This sensor has the advantages of improved stability and a
      simplified manufacturing procedure. An adduct of glucose and 4-vinylphenylboronic
      acid (VPBA) was synthesized by esterification and was then purified. The
      copolymer of the glucose/VPBA adduct and methylene bisacrylamide was grafted onto
      an indium tin oxide electrode surface. Glucose was washed out from the copolymer
      to obtain an MIP layer. Cyclic voltammetry of ferrocyanide in aqueous solution
      was performed using an MIP-grafted electrode, and the effect of glucose on the
      anodic current intensity was evaluated. The anodic current intensity was
      sensitive to the glucose concentration, and the dynamic range (0-900 mg/dl)
      covered the typical range of diabetic blood glucose levels. The response time of
      the MIP-grafted electrode to a stepwise change in the glucose concentration was
      approximately 3-5 min. Thus, we can conclude that, by taking advantage of its
      gate effect, it is feasible to use an MIP-grafted electrode as a glucose sensor
      for monitoring blood sugar in diabetic patients.

PMID- 20035401
TI  - Ventricular assist device infection necessitating device exchange following
      extensive myocardial resection.
AB  - A 14-year-old boy undergoing long-term mechanical circulatory support with a left
      ventricular assist device (LVAD) developed myocardial abscess resulting from
      cannula exit-site infection. This critically ill patient was successfully treated
      with LVAD replacement and omentopexy following extensive myocardial debridement.
      Although the use of artificial materials in the face of active infection is not
      ideal, other options including LVAD explantation or urgent heart transplantation
      are not always feasible depending on the patient's cardiac function and the
      availability of a donor heart. Under such circumstances, LVAD replacement might
      be the only measure available that could save patients who otherwise would not
      survive.

PMID- 20035402
TI  - Bone regeneration within a tailor-made tricalcium phosphate bone implant with
      both horizontal and vertical cylindrical holes transplanted into the skull of
      dogs.
AB  - A new tailor-made bone implant (TI) with six horizontal cylindrical holes
      fabricated from alpha-tricalcium phosphate powder, as described in our previous
      report, was modified to include five additional vertical holes (TI-v) in an
      attempt to accelerate the bone regeneration through the holes. This TI-v implant
      and hydroxyapatite implants (HI) as controls were transplanted into experimental
      skull defects in dogs. Computed tomography (CT) was performed immediately after
      the surgery and then every 4 weeks. The dogs were killed for histological
      analysis at 24 weeks of implantation. On CT, bone bridging between the implant
      and the skull was observed in the TI-v group from 8 weeks of implantation,
      whereas a clear bone bridge was not formed in the HI group after 24 weeks of
      implantation. Histological analysis revealed collagen tissues and new bone
      formation in the horizontal cylindrical holes in most of the TI-v group, whereas
      mainly connective tissues invaded the porous structures in the HI group. In the
      Ti-v group, at the middle of the horizontal holes where they crossed the vertical
      holes, fibrous collagen tissues and muscular tissue filled up the hole and new
      bone formation seemed to be blocked. However, in the TI-v group more collagen and
      bone tissues were formed than in the HI group; when compared with the data in our
      previous report, however, the total volume of regenerated bone in the horizontal
      cylindrical holes in the TI-v seemed to be less than that in the TI. Thus, the
      addition of vertical cylindrical holes in the TI-v was not effective in promoting
      the faster stabilization of the TI-v in the skull of the dog.

PMID- 20035403
TI  - Extracorporeal circulation technical training DVD volume 1: basic operation and
      troubleshooting scenarios.

PMID- 20035404
TI  - The role of intravascular intervention in the management of Budd-Chiari syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of intravascular intervention in the
      management of different types of Budd-Chiari syndrome. METHODS: Fifty-three
      patients of BCS were clinically diagnosed and interventionally treated in terms
      of their signs and symptoms of portal hypertension and occlusive inferior vena
      cava/or hepatic veins with the combination of Doppler ultrasonography, CT scan,
      and angiography. The interventional methods applied in this study included
      percutaneous transluminal angioplasty and IVC stent implantation (PTA+IVC stent);
      transjugular hepatic veno-stent placement (PTA+HV stent) or transjugular
      transluminal hepatic veno-inferior vena cava stent placement and transcaval
      transjugular intrahepatic portocaval shunt. RESULTS: The success rate of
      intravascular interventional therapy was 92.45% (49/53). After interventional
      therapy, the patients' pleural effusion, ascites, prominent veins formation of
      bilateral flanks or backs alleviated, hepatomegaly reduced, and the urinary
      output increased. The longest follow-up case was 13 years with patent stent. Two
      patients died of pulmonary embolization or pericardial tamponade during surgery.
      CONCLUSION: Intravascular intervention is a safe and effective therapy for most
      types of BCS.

PMID- 20035405
TI  - "You are our only hope": trading metaphorical "magic bullets" for stem cell
      "superheroes".
AB  - In the wake of two recent developments in stem cell research, it is a fitting
      time to reassess the claim that stem cells will radically transform the concept
      and function of medicine. The first is the U.S. Food and Drug Administration's
      decision in January 2009 to approve Geron Corporation's Phase I clinical trial
      using human embryonic stem cells for patients with spinal cord injuries. The
      second is the National Institutes of Health's decision to permit federal funding
      of research using donated IVF human embryos in their July 2009 Guidelines on
      Human Stem Cell Research. We are now poised to see whether stem cell research can
      deliver on what it promises. However, what exactly does it promise and how?
      Moreover, who is doing the promising? Turning to the use of metaphor can help us
      to answer these questions and enable us to develop a better appreciation of the
      unique features of promised stem cell therapies. Indeed, metaphors have exerted
      profound influence in medicine, and it is fitting that we seek new metaphors for
      new therapies where appropriate. In this case, other metaphors such as magic
      bullets or the Holy Grail cannot capture what is unique about stem cells.
      Accordingly, I propose a new metaphor: the stem cell superhero. Stem cell
      superheroes are characterized by the following traits: they are seemingly capable
      of fighting the evil of virtually all disease (unlike "magic bullets") and they
      seem to be our only hope of doing so, although to summon them we must make
      difficult moral choices. In the course of assessing the merits of three recent
      yet covert references to the superhero metaphor, I conclude that this powerful
      new paradigm employs a problematic logic (i.e., we cannot know that something is
      "our only hope"), but that the aspiration as such is a good one.

PMID- 20035410
TI  - MR imaging findings of benign and malignant circumscribed breast masses: part 1.
      Solid circumscribed masses.
AB  - The purpose of our study was to review the magnetic resonance (MR) imaging
      findings and pathological diagnoses of benign and malignant solid circumscribed
      breast masses. This article reviews the MR imaging findings of solid
      circumscribed breast masses. A strategy for the diagnosis of solid circumscribed
      breast masses with MR imaging is herein presented that incorporates the signal
      intensity characteristics on T(1)- and T(2)-weighted images with the kinetic
      curve assessment reflected by the temporal and spatial uptake of contrast medium.

PMID- 20035411
TI  - MR imaging findings of benign and malignant circumscribed breast masses: part 2.
      Cystic circumscribed masses.
AB  - The purpose of our study was to review the magnetic resonance (MR) imaging
      findings and pathological characteristics of benign and malignant cystic
      circumscribed breast masses. This article reviews the MR imaging findings of
      cystic circumscribed breast masses. Intracystic papillomas typically show a
      single mural nodule with a washout enhancement pattern. Intracystic papillary
      carcinomas show multiple mural nodules or grow as a solid mass that obliterates
      the cystic space with a washout enhancement pattern. Despite the MR imaging
      findings, however, many circumscribed breast masses are impossible to
      differentiate without performing a biopsy.

PMID- 20035412
TI  - Results of a dummy run of postimplant dosimetry between multi-institutional
      centers in prostate brachytherapy with 125I seeds.
AB  - PURPOSE: To determine the reproducibility and precision of postimplant dosimetry
      following (125)I prostate brachytherapy (PB) and to evaluate the effects of
      learning and experience in CT-based postimplant dosimetry. MATERIALS AND METHODS:
      One-month postimplant CT data from two patients who underwent PB alone or
      combined therapy (PB + EBRT) were sent to 28 institutions for postimplant
      dosimetry and analyzed in 2006 (study 1). Similarly, 1-month postimplant CT data
      from two other patients were also analyzed in 2008 (study 2; 23 institutions).
      For both modalities in studies 1 and 2, the variance of the difference between CT
      based D90 at each institution and CT/MRI fusion-based D90 was estimated. RESULTS:
      In monotherapy, F test and Mann-Whitney U test revealed no significant difference
      in the variance in studies 1 and 2 (P = 0.72, 0.46). In combined therapy, the
      variance significantly converged in study 2 compared with study 1 (P < 0.05).
      Even in the two studies, however, the difference between the median CT-based D90
      and fusion-based D90 was at least 20-30 Gy. CONCLUSION: Marked interobserver
      variability was seen in the prostate volume and D90 with CT alone. The precision
      of postimplant dosimetry based on CT alone was revealed to be limited.

PMID- 20035413
TI  - Size of noncancerous hilomediastinal lymph nodes measured on coronal and sagittal
      reconstruction CT images.
AB  - PURPOSE: To determine the sizes of hilomediastinal lymph nodes on coronal and
      sagittal reconstruction computed tomographic images of subjects without known
      malignancies. MATERIALS AND METHODS: We evaluated 560 lymph nodes of 246
      consecutive patients who underwent multidetector-row computed tomography (MDCT)
      of the chest, then reconstructed coronal and sagittal images on a viewer and
      measured short-axis diameters of lymph nodes in each station according to the
      American Thoracic Society (ATS) map for axial, coronal, and sagittal images.
      RESULTS: On coronal images, short-axis diameters were significantly larger than
      on axial images in station #4R (P < 0.01). On sagittal images, short-axis
      diameters were significantly smaller than on axial images in stations #4L (P <
      0.01), #10R (P < 0.001), and #10L (P < 0.05). On coronal and sagittal images,
      short-axis diameters were significantly smaller than on axial images in stations
      #11R (P < 0.001). In #7, diameters were significantly larger on coronal images
      than on axial and sagittal images (P < 0.001), and diameters were significantly
      smaller on sagittal images than on axial images (P < 0.01). CONCLUSION: In
      stations #4R, #4L, #7, #10R, #10L, and #11R, measurements of short-axis diameters
      of hilomediastinal lymph nodes differed on coronal and sagittal images. On
      coronal and sagittal images, evaluation of hilomediastinal lymph nodes requires
      unique size criteria for every station.

PMID- 20035414
TI  - Defining juxtapapillary diverticulum with 3D segmented trueFISP MRCP: comparison
      with conventional MRCP sequences with an oral negative contrast agent.
AB  - PURPOSE: To compare three-dimensional segmented true fast imaging with steady
      state precession magnetic resonance cholangiopancreatography (3D-trueFISP-MRCP)
      to conventional MRCP sequences with an oral negative contrast agent for
      diagnosing juxtapapillary diverticulum. MATERIALS AND METHODS: A total of 42
      patients with (n = 21) and without (n = 21) juxtapapillary diverticulum confirmed
      by endoscopic retrograde cholangiopancreatography (ERCP) were evaluated. Three
      MRCP sequences, 3D-trueFISP-MRCP, two-dimensional rapid acquisition with
      relaxation enhancement MRCP (2D-RARE-MRCP), and 3D T(2)-weighted turbo spin-echo
      MRCP (3D-TSE-MRCP), obtained after administering an oral negative contrast agent
      (FerriSeltz; Otsuka Pharmaceutical, Tokushima, Japan) were compared. Two
      radiologists independently and blindly interpreted the presence or absence of
      juxtapapillary diverticulum and its positional relationship against the papilla.
      The detectability of juxtapapillary diverticulum of each sequence as decided by
      consensus was then compared. Kappa statistics were used to measure interobserver
      agreement of the classifications. RESULTS: The sensitivity, specificity, and
      accuracy for detecting juxtapapillary diverticulum of 3D-trueFISPMRCP (61.9%,
      85.7%, and 73.8%) were substantively higher than those of 2D-RARE-MRCP (0.0%,
      100%, and 50.0%) and 3D-TSE-MRCP (9.5%, 100%, and 54.8%). Interobserver agreement
      of the position of juxtapapillary diverticulum by 3D-trueFISP-MRCP was good
      (kappa = 0.55). CONCLUSION: 3D-trueFISP-MRCP can define juxtapapillary
      diverticulum even with an oral negative contrast agent, whereas conventional MRCP
      sequences cannot.

PMID- 20035415
TI  - Imaging findings and management of isolated dissection of the visceral arteries.
AB  - PURPOSE: To describe clinical and computed tomography (CT) findings of isolated
      dissection of the visceral arteries (IDVA). MATERIALS AND METHODS: We
      retrospectively analyzed clinical presentation and abdominal CT findings of 38
      patients who were diagnosed as having an IDVA. IDVA were classified into three
      types based on CT findings: patent false lumen with re-entry (type I), patent
      false lumen without re-entry (type II), and completely thrombosed false lumen
      (type III). RESULTS: The dissection was located in the superior mesenteric artery
      (SMA) in 27 patients, celiac artery (CA) in 6, CA to splenic artery in 2, and
      common hepatic artery (CHA), CA to CHA, and inferior mesenteric artery (IMA) in 1
      patient each. The dissection was classified into type I in 8 patients, type II in
      12, and type III in 18. Surgical treatment was performed in 1 patient with type
      II SMA dissection because of bowel ischemia, although the remaining 37 patients
      were managed conservatively. Two cases with type II showed a progressive
      enlargement of the false lumen in follow-up CT. Increased density of the fat
      tissue around the affected visceral artery was more commonly seen in symptomatic
      patients compared to asymptomatic ones (P < 0.01). CONCLUSION: Based on our
      observation, patients with IDVA can be managed conservatively when there are no
      signs indicating organ ischemia.

PMID- 20035416
TI  - Radiologic-pathological correlation of punctate hyperechoic foci by ultrasound in
      stereotactic vacuum-assisted breast biopsy samples.
AB  - PURPOSE: To correlate punctate hyperechoic foci (PHF) on ultrasound (US) with
      microcalcifications detected by mammography (MMG) and at histopathology.
      MATERIALS AND METHODS: Forty-eight subjects who underwent stereotactic vacuum
      assisted breast biopsy (SVABB) for evaluation of breast microcalcifications
      between April and December 2008 were evaluated for 191 lesions obtained after
      SVABB. The concordance between PHF on US with microcalcifications detected on MMG
      and histopathology was therefore evaluated for 191 lesions. Values for
      sensitivity and specificity were determined against histopathology as the
      reference standard. RESULTS: In 154 of 191 samples (80.6%), the PHF on US
      corresponded with microcalcifications on MMG and histopathology. The overall
      sensitivity and specificity were 85.3% and 80.0%, respectively, for US, and 89.7%
      and 90.7%, respectively, for MMG. There were no significant differences between
      values for US and MMG. At US, 12 PHF did not correlate with any
      microcalcifications at MMG or histopathology. Histopathology revealed collagen
      fibers in fatty tissue in 5 of 12 lesions and collagenization in 2 of 12 lesions.
      CONCLUSION: There was a general concordance between PHF on US and
      microcalcifications detected at MMG. However, in addition to microcalcifications,
      collagen fibers in fatty tissue and collagenization may account for some PHF.
      This possibility should be considered when interpreting US findings.

PMID- 20035417
TI  - Evaluation of rectal bleeding factors associated with prostate brachytherapy.
AB  - PURPOSE: To analyze rectal bleeding prognostic factors associated with prostate
      brachytherapy (PB) or in combination with external-beam radiation therapy (EBRT)
      and to examine dosimetric indications associated with rectal bleeding. MATERIALS
      AND METHODS: The study included 296 patients followed up for >36 months (median,
      48 months). PB was performed alone in 252 patients and in combination with EBRT
      in 44 patients. PB combined with EBRT is indicated for patients with a Gleason
      score >6. The prescribed dose was 144 Gy for monotherapy and 110 Gy for PB + EBRT
      (44-46 Gy). RESULTS: Although 9.1% who received monotherapy had 2.3% grade 2
      rectal bleeding, 36.3% who received combined therapy had 15.9% grade 2 rectal
      bleeding. Combined therapy was associated with higher incidence of rectal
      bleeding (P = 0.0049) and higher percentage of grade 2 bleeding (P = 0.0005).
      Multivariate analysis revealed that R-150 was the only significant factor for
      rectal bleeding, and modified Radiation Therapy Oncology Group (RTOG) grade in
      monotherapy and biologically equivalent dose (BED) were significant for combined
      therapy. Moreover, grade 2 rectal bleeding increased significantly at D90 > 130
      Gy. CONCLUSION: Although R-150 was the significant prognostic factor for rectal
      bleeding and modified RTOG rectal toxicity grade, BED was the significant
      prognostic factor for modified RTOG rectal toxicity grade.

PMID- 20035418
TI  - Analysis of stereotactic vacuum-assisted breast biopsy for patients with
      segmental calcifications.
AB  - PURPOSE: To evaluate the results of stereotactic vacuum-assisted breast biopsy of
      segmental calcifications. MATERIAL AND METHODS: Thirty-nine lesions with
      segmental calcifications after the exclusion of malignant calcifications of
      category 5 were evaluated. Calcifications were classified morphologically into
      small, round, and amorphous calcifications. Lesions in which small round and
      amorphous calcifications were mixed were classified into small round dominant and
      amorphous dominant calcifications. The density of distribution of calcifications,
      heterogeneity in size, and heterogeneity in density were also classified
      visually, and the correlations of these categories with the biopsy findings were
      evaluated. RESULTS: The calcifications were classified into 10 with small round
      calcifications (26%), 10 with small round calcifications dominant (26%), 12 with
      amorphous calcifications dominant (30%), and 7 with amorphous calcifications
      (18%). The pathological findings of biopsy specimens were benign in 27 lesions
      (69%), borderline in 1 (3%), and malignant in 11 (28%). Lesions with mixed
      calcifications in which amorphous calcifications were dominant were more often
      malignant. Lesions with calcifications showing a high distribution density and
      those with calcifications heterogeneous in density were more often malignant.
      CONCLUSION: Lesions with heterogeneous calcifications are frequently malignant,
      and biopsy should be considered.

PMID- 20035419
TI  - Metastasis of humeral osteosarcoma to the contralateral breast detected by 99mTc
      MDP skeletal scintigraphy.
AB  - A rare case of osteogenic sarcoma (OGS) of the left humerus metastasizing to the
      right breast is presented. This lesion was detected by serendipitous observation
      on (99m)Tc-MDP skeletal scintigraphy that demonstrated a rounded focus just
      outside the skeletal outline of the right chest. The focus remained at a similar
      location on repeat postwash view. Clinical examination revealed a breast mass
      corresponding to the site of uptake, and a biopsy of this mass revealed it to be
      a metastasis of osteogenic sarcoma. The present case demonstrates a rare site of
      metastasis from OGS of the left humerus to the contralateral breast and hence is
      reported here as an unusual case vignette.

PMID- 20035420
TI  - A case of metastatic malignant melanoma of the ovary with a multilocular cystic
      appearance on MR imaging.
AB  - Ovarian metastasis from malignant melanoma is rare and usually appears as a solid
      ovarian mass. We report a case of ovarian metastasis from cutaneous malignant
      melanoma that proved to be a diagnostic dilemma. The ovarian metastasis exhibited
      a multilocular cystic appearance on magnetic resonance imaging, mimicking a
      mucinous ovarian tumor with massive ascites.

PMID- 20035421
TI  - Malignant rhabdoid tumor of the liver: a case report with US and CT
      manifestation.
AB  - A case of malignant rhabdoid tumor (MRT) of the liver in a 4-month-old boy with
      hepatomegaly was described with the help of US and CT findings. The boy had
      multiple liver tumors, and the liver parenchyma showed a diffuse heterogeneous
      appearance. Lymph node swelling was noted, although the alpha-fetoprotein
      concentration was not elevated. A diagnosis of MRT was confirmed pathologically.
      Twenty-seven cases of MRT of the liver with solitary tumors, multiple tumors, or
      diffuse infiltration have been reported in the English-language literature.
      Diagnostic imaging plays an important role in detecting metastasis because of the
      high frequency of distant metastasis in MRT of the liver.

PMID- 20035422
TI  - Agricultural productivity changes induced by the sloping land conversion program:
      an analysis of Wuqi county in the Loess Plateau region.
AB  - This paper examines the agricultural productivity change induced by the Sloping
      Land Conversion Program (SLCP) using the Malmquist index method and household
      data collected from Wuqi. We find that during the period of 1998-2004, the total
      factor productivity (TFP) grew by 15.8%. While numerous households suffered a TFP
      decline, the majority of them experienced a large gain. By decomposing the TFP,
      we further show that its increase is due exclusively to the improvement of
      technical efficiency rather than to technological change. To validate these
      findings and put them in perspective, we also estimated the TFP change with
      county-level aggregate data. It is revealed that driven by technological change
      and scale efficiency, the TFP grew slightly during the period of 1992-1998.
      Because of the tremendous cropland reduction and production mode shift caused by
      implementing the SLCP, the TFP declined substantially during the first three
      years of the program; due to continued improvement of technical efficiency;
      however, its growth accelerated later. Altogether, our evidence consistently
      suggests that implementing the SLCP has contributed to the agricultural TFP
      growth in the longer term and that the efficiency improvement has resulted mainly
      from the increased public expenditures for extension services and diffusion of
      technical knowledge. Wuqi's experience proves that it is possible to achieve
      environmental conservation and increase productivity simultaneously, even when
      facing a cropland reduction and production mode alternation.

PMID- 20035423
TI  - Inhibition of experimental colorectal cancer and reduction in renal and
      gastrointestinal toxicities by copper-indomethacin in rats.
AB  - PURPOSE: To evaluate, for the first time, the efficacy of copper-indomethacin in
      the inhibition of aberrant crypt foci formation using the azoxymethane-induced
      adenocarcinoma model, to examine cell viability in the HCT-116 colorectal cancer
      cell line, gastrointestinal permeability, mitochondrial oxidative damage, and
      renal toxicity in rat models. METHODS: Azoxymethane-induced adenocarcinoma rats
      were dosed with indomethacin and copper-indomethacin for 28 days and aberrant
      crypt foci were evaluated. HCT-116 colorectal cancer cells were exposed to
      indomethacin and copper-indomethacin at 0-250 microg/mL (0-698 microM for
      indomethacin, and 0-147 microM for copper-indomethacin), and cell viability was
      measured. Acute gastrointestinal toxicity was measured using gastrointestinal
      permeability markers, gastrointestinal ulceration and bleeding, and measurement
      of an acute-phase protein haptoglobin. Effects of acute and chronic
      administration of indomethacin and copper-indomethacin on urinary electrolyte
      concentrations were examined. RESULTS: Both indomethacin and copper-indomethacin
      resulted in a significant reduction in aberrant crypt foci in azoxymethane
      treated rats. In parallel, high concentrations of indomethacin and copper
      indomethacin also reduced cell viability in HCT-116 colorectal cancer cells.
      However, copper-indomethacin was considerably safer in all measures of
      gastrointestinal toxicity compared to indomethacin. In addition, indomethacin
      reduced urinary electrolytes at an ulcerogenic dose of 10 mg/kg acutely and
      chronically at 3.0 mg/kg for 28 days, whereas copper-indomethacin at equimolar
      doses of indomethacin affected urine electrolytes after acute dosing but not
      after chronic dosing for 28 days. CONCLUSIONS: Copper-indomethacin has both
      gastrointestinal and renal sparing properties while maintaining efficacy in
      experimental adenocarcinoma.

PMID- 20035424
TI  - Successful rechallenge with erlotinib in a patient with EGFR-mutant lung
      adenocarcinoma who developed gefitinib-related interstitial lung disease.
AB  - Small-molecule tyrosine kinase inhibitors (TKIs) targeting the epidermal growth
      factor receptor (EGFR) pathways are used clinically for patients with non-small
      cell lung cancer (NSCLC). It is well established that somatic mutations in the
      kinase domain of the EGFR (Lynch et al. in N Engl J Med 350:2129-2139, 2004; Paez
      et al. in Science 304:1497-1500, 2004) are strongly associated with the tumor
      response and clinical outcomes in patients with NSCLC receiving EGFR-TKIs
      (Mitsudomi and Yatabe in Cancer Sci 98:1817-1824, 2007). Although the most common
      adverse events are skin rash and diarrhea, the most serious adverse effect
      reported is drug-related interstitial lung disease (ILD) (Inoue et al. in Lancet
      361:137-139, 2003; Ando et al. in J Clin Oncol 24:2549-2556, 2006). The precise
      mechanism underlying the development of drug-related ILD remains unknown. Here,
      we describe a case of EGFR-mutant NSCLC who was rechallenged with the small
      molecule EGFR antagonist erlotinib after developing gefitinib-related ILD.

PMID- 20035425
TI  - Impact of functional ABCG2 polymorphisms on the adverse effects of gefitinib in
      Japanese patients with non-small-cell lung cancer.
AB  - PURPOSE: ABCG2 is a half-size ATP-binding cassette transporter implicated in
      cellular gefitinib transport. Reportedly, the c.421C > A ABCG2 gene polymorphism
      was associated with gefitinib-induced diarrhea in Caucasian patients with non
      small-cell lung cancer. Since c.421C > A ABCG2, resulting in p.Q141K
      substitution, is more prevalent in Asian populations, the putative relationship
      between gefitinib-induced adverse effects and this functional polymorphism was
      investigated in Japanese patients. c.376C > T, resulting in truncated, non
      functional ABCG2, was also investigated. METHODS: ABCG2 gene polymorphisms were
      evaluated in 75 patients with non-small-cell lung cancer treated with gefitinib
      250 mg/day orally, and results were correlated with treatment-related adverse
      effects. RESULTS: Forty (53.3%) patients harbored c.421A ABCG2 on at least one
      allele, while the remaining 35 (46.7%) were wild type for c.421C > A. No
      significant group difference was observed in frequency of gefitinib-related
      diarrhea or other adverse effects. In addition, the only one patient homozygous
      for the c.421A allele in this study was not affected with gefitinib-induced
      diarrhea or interstitial lung disease. Two patients (2.7%) were found to harbor
      the c.376T allele heterozygously. One of the two patients harbored both the
      c.376T and the c.421A genotypes on distinct alleles. Gefitinib-related
      interstitial lung disease and severe diarrhea were noted in neither of the two
      patients. CONCLUSIONS: In this Japanese population, we did not find an evident
      association between ABCG2 polymorphisms, c.376C > T and c.421C > A, and
      susceptibility to gefitinib-induced adverse effects.

PMID- 20035426
TI  - Down-regulation of heat shock protein 70 improves arsenic trioxide and 17-DMAG
      effects on constitutive signal transducer and activator of transcription 3
      activity.
AB  - PURPOSE: Signal transducer and activator of transcription 3 (STAT3) has been
      shown to be constitutively active in approximately 50% of patients with acute
      myeloid leukemia and is associated with worse outcome. Arsenic trioxide (ATO)
      synergizes with the heat shock protein (HSP) 90 inhibitor, 17-DMAG, to down
      regulate STAT3 activity. However, both agents up-regulate HSP70, an anti
      apoptotic protein. We therefore examined whether down-regulating HSP70 with short
      interference (si) RNA will affect ATO and 17-DMAG effects on constitutive STAT3
      activity. EXPERIMENTAL DESIGN: A semi-mechanistic pharmacodynamic model was used
      to characterize concentration-effect relationships of ATO and 17-DMAG effects on
      constitutive STAT3 activity and HSP70 expression with or without siRNA against
      HSP70 in a cell line model. RESULTS: Treatment with siRNA for HSP70 resulted in a
      stronger degree of synergism on down-regulation of STAT3 activity by ATO and 17
      DMAG. However, treatment with siRNA for HSP70 resulted in less synergism on up
      regulation of HSP70 by the two drugs. CONCLUSIONS: Down-regulation of HSP70
      improves ATO and 17-DMAG effects on constitutive STAT3 activity. These results
      further provide a basis for studying the combined role of ATO with a HSP90
      inhibitor such as 17-DMAG in AML with constitutive STAT3 activity.

PMID- 20035427
TI  - New alternatives for laser vaporization of the prostate: experimental evaluation
      of a 980-, 1,318- and 1,470-nm diode laser device.
AB  - PURPOSE: Several diode laser systems were introduced in recent years for the
      minimal-invasive surgical therapy of benign prostate enlargement. We investigated
      the ablation capacities, hemostatic properties and extend of tissue necrosis of
      different diode lasers at wavelengths of 980, 1,318 and 1,470 nm and compared the
      results to the 120 W GreenLight HPS laser. METHODS: The laser devices were
      evaluated in an ex vivo model using isolated porcine kidneys. The weight
      difference of the porcine kidneys after 10 min of laser vaporization defined the
      amount of ablated tissue. Blood loss was measured in blood-perfused kidneys
      following laser vaporization. Histological examination was performed to assess
      the tissue effects. RESULTS: The side-firing 980 and 1,470 nm diode lasers
      displayed similar ablative capacities compared to the GreenLight HPS laser
      (n.s.). The 1,318-nm laser, equipped with a bare-ended fiber, reached a higher
      ablation rate compared to the other laser devices (each P < 0.05). A calculated
      'output power efficiency per watt' revealed that the 1,318-nm laser with a bare
      ended fiber reached the highest rate compared to the side-firing devices (each P
      < 0.0001). All three diode lasers showed superior hemostatic properties compared
      to the GreenLight HPS laser (each P < 0.01). The extend of morphological tissue
      necrosis was 4.62 mm (1,318 nm), 1.30 mm (1,470 nm), 4.18 mm (980 nm) and 0.84 mm
      (GreenLight HPS laser), respectively. CONCLUSION: The diode lasers offered
      similar ablative capacities and improved hemostatic properties compared to the
      120 W GreenLight HPS laser in this experimental ex vivo setting. The higher
      tissue penetration of the diode lasers compared to the GreenLight HPS laser may
      explain improved hemostasis.

PMID- 20035428
TI  - Human skin-derived mesenchymal stem cells as a source of VEGF and nitric oxide.
AB  - Researches on stem cells bring promise to functional skin repair. In particular,
      it has been recently suggested that mesenchymal stem cells (MSCs) could
      positively affect cutaneous wound healing through differentiation and paracrine
      action. The molecular mechanisms are not clear, even if there is increasing
      evidence for an important action of nitric oxide (NO), probably mediated by the
      regulation of the gene encoding for vascular endothelial growth factor (VEGF).
      The aim of our study was to investigate the immunohistochemical expression of
      VEGF and nitric oxide synthase (NOS) isoforms in human skin-derived MSCs, as well
      as the production of VEGF and NO, because these cells are less well characterized
      than bone marrow MSCs. MSCs were obtained from skin biopsies of healthy adult
      patients undergoing cosmetic plastic surgery, expanded and characterized for
      specific surface antigens. The cells were then evaluated for the
      immunohistochemical expression of VEGF, and NOS isoforms, as well as for VEGF and
      NO secretion in cell culture medium. Our immunohistochemical analysis showed that
      proliferating MSCs derived from human skin exhibit VEGF expression at cytoplasmic
      level as well as cytosolic and nuclear localization of all the three isoforms of
      NOS, even if with different patterns. In addition, our data evidenced the release
      of both VEGF and NO in cell culture supernatants. In conclusion, our results
      suggest that a therapeutic approach based on the human skin-derived MSCs may have
      a positive effect in wound healing conditions, through their ability to provide
      VEGF and NO to the damaged area.

PMID- 20035429
TI  - Apolipoprotein epsilon4 allele and psoriasis severity.

PMID- 20035430
TI  - Antibodies and neuronal autoimmune disorders of the CNS.
AB  - We review the neuronal antibodies described in CNS disorders in order to clarify
      their diagnostic value, emphasize potentials pitfalls and limitations in the
      diagnosis of paraneoplastic neurological syndromes (PNS), and examine the current
      evidence for a possible pathogenic role. We propose to classify the neuronal
      antibodies associated with syndromes resulting from CNS neuronal dysfunction into
      two groups according to the location of the antigen: inside the neuron or in the
      cell membrane. Group I includes antibodies which target intracellular antigens
      and probably are not pathogenic. They are further subdivided into three groups.
      Group Ia comprises well-characterized onconeural antibodies (Hu (ANNA1), Yo
      (PCA1), Ri (ANNA2), CV2 (CRMP5), amphiphysin, Ma2) that are useful for the
      diagnosis of PNS. Group Ib antibodies (SOX and ZIC) are cancer-specific but there
      is no evidence that the immune response is in any way pathogenically related to
      the PNS. Antibodies in group Ic (glutamic acid decarboxylase (GAD), adenylate
      kinase 5 and Homer 3) identify non-PNS: stiff-person syndrome (SPS), cerebellar
      ataxia, and limbic encephalitis (LE). Group II antibodies recognize neuronal
      surface antigens. Antibodies in group IIa associate with characteristic CNS
      syndromes but their detection does not indicate that the disorder is
      paraneoplastic. Antibodies to potassium channels, AMPA and GABA(B) receptors are
      associated with LE, NMDA receptor antibodies identify a well-defined
      encephalitis, and antibodies against glycine receptors associate with SPS with
      encephalitis. A pathogenic role of the antibodies is suggested by the response of
      symptoms to immunotherapy and the correlation between antibody titers and
      neurological outcome. Lastly, Group IIb includes antibodies that are found in
      patients with paraneoplastic cerebellar ataxia associated with lung cancer (P/Q
      type calcium channels antibodies) or Hodgkin disease (metabotropic glutamate
      receptor type 1 antibodies).

PMID- 20035431
TI  - Investigation of TNFA 308G > A and TNFB 252G > A polymorphisms in genetic
      susceptibility to migraine.
AB  - We aimed to look for the association of tumor necrosis factor (TNF) gene
      polymorphisms (TNFA 308G > A, and TNFB 252G > A) in genetic susceptibility to
      migraine. The pathogenesis of migraine involves many immune-mediated mechanisms
      in the vascular endothelium. TNF, being a potent immunomodulator and pro
      inflammatory cytokine, is suggested to be involved in inflammatory reactions
      leading to migraine attacks. A total of 216 normotensive migraine patients, 160
      tension type headache (TTH) patients and 216 healthy controls (HC) were recruited
      in the study. The genetic polymorphisms were investigated through SNP association
      analysis using a matched case control migraine population. Genotyping of TNFA
      308G > A polymorphism and TNFB 252G > A was done using ARMS PCR and PCR-RFLP,
      respectively. A borderline association was observed in TNFA 308GA genotype in
      migraine patients versus HC (p = 0.043; OR = 1.763; 95% CI = 1.019-3.051). After
      sub-grouping migraine into migraine with aura (MA) or without aura, significant
      difference at genotypic (p = 0.015; OR = 2.293; 95% CI = 1.172-4.487) as well as
      allelic (p = 0.035; OR = 1.955; 95% CI = 1.047-3.651) level was evident. The
      difference was even more significant in female MA at genotypic (p = 0.006; OR =
      2.901; 95% CI = 1.361-6.181) and allelic level (p = 0.017; OR = 2.318; 95% CI =
      1.159-4.635) as well as for A allele carriers in MA [p value = 0.020; OR = 2.205
      (1.132-4.295)] and female MA (p value = 0.008; OR = 2.741; CI = 1.297-5.792). No
      association of TNFB252G > A was observed in migraine patients or any subgroups.
      We did not find any association of TNFA or TNFB gene polymorphisms with TTH. In
      conclusion, the TNFA 308G > A polymorphism was found to be associated with MA,
      particularly in females, whereas we could not find any association of TNFB 252G >
      A polymorphism in genetic susceptibility to migraine on comparing the migraine
      patients with HC or TTH patients.

PMID- 20035432
TI  - Asbestos exposure and malignant lymphoma: a multicenter case-control study in
      Germany and Italy.
AB  - AIMS: To analyze the relationship between asbestos exposure and malignant
      lymphoma in a multicenter case-control study conducted in Germany and Italy
      according to a common core protocol. METHODS: Male and female patients with
      malignant lymphoma (n = 1,034) between 18 and 80 years of age were prospectively
      recruited in six study areas in Germany (Ludwigshafen/Upper Palatinate,
      Heidelberg/Rhine-Neckar-County, Wurzburg/Lower Frankonia, Hamburg, Bielefeld/East
      Westphalia, and Munich) and in two study areas in Sardinia, Italy (Cagliari and
      Nuoro provinces). A total of 1,173 population control subjects were drawn from
      population registers. In a structured personal interview, we elicited a complete
      occupational history, including every occupational period that lasted at least 1
      year. On the basis of job task-specific supplementary questionnaires, trained
      experts assessed the exposure to asbestos. As a measure of cumulative asbestos
      exposure on a time by intensity scale, fiber-years were calculated. 12 cases
      (1.2%) and 12 control subjects (1.0%) had a cumulative asbestos exposure of more
      than 2.6 fiber-years (highest exposure category according to the 90th percentile
      of exposed control subjects). Odds ratios (OR) and 95% confidence intervals (CI)
      were calculated using unconditional logistic regression analysis adjusted for
      age, sex and study region. Patients with specific lymphoma sub-entities were
      additionally compared with the entire control group. RESULTS: We observed no
      statistically significant association between cumulative asbestos exposure and
      the risk of any lymphoma subtype. An elevated risk was found for the association
      between exposure to more than 2.6 fiber-years and multiple myeloma (OR = 6.0; 95%
      CI 1.4-25.1); however, numbers were small (n = 3 cases, all of them from Italy; n
      = 12 control subjects). CONCLUSIONS: Our study does not support an association
      between asbestos exposure and risk of malignant lymphoma.

PMID- 20035433
TI  - Assaults against nurses of general and psychiatric hospitals in Taiwan.
AB  - PURPOSE: Nurses are at risk of occupational assaults. However, the incidence and
      effects have not been documented among nurses in Taiwan. We aimed to study the
      incidence of assaults and their effects, including quality of life and job
      related stress among nurses. METHODS: A cross-sectional study was conducted to
      understand the incidence of work-related assaults in nurses. Job content
      questionnaire was used to determine the job control, psychological demands at
      work, and workplace support in these nurses. Quality of life was assessed by
      short form-36 (SF-36). RESULTS: A total of 842 nurses satisfactorily completed
      the questionnaire, including 375 from general hospitals and 467 from psychiatric
      hospitals. A total of 237 (28.1%) reported to have experienced physical and/or
      verbal assaults in past 6 months. Experiences of sexual assault or verbal abuse
      were risk factors for feeling threatened by potential attacks. Nurses who felt
      threatened by potential attacked scored lower in general health, mental health,
      and vitality by SF-36, and had higher psychological demands at work, lower job
      control, and lower workplace support. CONCLUSION: We conclude that nurses in
      general and psychiatric hospitals had high risk of assaults. Worksite assaults
      caused nurses to feel threatened, and such an effect was likely to cause
      increased job stress and decreased quality of life.

PMID- 20035434
TI  - Spring vegetation phenology is a robust predictor of breeding date across broad
      landscapes: a multi-site approach using the Corsican blue tit (Cyanistes
      caeruleus).
AB  - The regulation of reproductive schedules is an important determinant of avian
      breeding success. In heterogeneous environments, the optimal breeding period may
      fluctuate temporally across habitats, often on a spatial scale much shorter than
      the average dispersal range of individuals. The synchronisation of reproductive
      events with the most favourable period at a given site therefore involves the
      integration of a suite of fine-scale environmental signals which contain
      information about future breeding conditions. In this study, we monitored clutch
      initiation date of blue tits (Cyanistes caeruleus) breeding in a wide range of
      environmental conditions (altitude, temperature regimes, habitat type) in Corsica
      (France) to understand the role of spring temperature and leafing phenology on
      the precise fine-tuning of egg laying on a local scale. Timing of breeding in
      blue tits was strongly correlated with phenology of the dominant vegetation (r(2)
      = 0.87). In contrast, spring temperature was not as robust a predictor of the
      timing of breeding, because a large part of the residual variation in egg-laying
      date was accounted by differences (ca. 2 weeks) in the development of the
      vegetation between habitat types (evergreen vs. deciduous oak forests). Female
      blue tits therefore appear to use the environmental variable (vegetation
      phenology) that is most closely linked to the future production of insect prey in
      order to accurately time laying over the entire spatio-temporal breeding
      landscape.

PMID- 20035435
TI  - Molecular keys unlock the mysteries of variable survival responses of blue crabs
      to hypoxia.
AB  - Hypoxia is a major stressor in coastal ecosystems, yet generalizing its impacts
      on fish and shellfish populations across hypoxic events is difficult due to
      variability among individuals in their history of exposure to hypoxia and related
      abiotic variables, and subsequent behavioral and survival responses. Although
      aquatic animals have diverse physiological responses to cope with hypoxia, we
      know little about how inter-individual variation in physiological state affects
      survival and behavioral decisions under hypoxic conditions. Laboratory
      experiments coupled with molecular techniques determined how extrinsic factors
      (e.g., water body and temperature) and respiratory physiology (hemocyanin
      concentration and structure) affected survival and behavior of adult blue crabs
      (Callinectes sapidus) exposed to different levels of hypoxia over a 30-h time
      period. Nearly 100% of crabs survived the 1.3 mg dissolved oxygen (DO) l(-1)
      treatment (18.4% air saturation), suggesting that adult blue crabs are tolerant
      of severe hypoxia. Probability of survival decreased with increasing hypoxic
      exposure time, lower DO, and increasing temperature. Individual-level differences
      in survival correlated with water body and crab size. Crabs collected from the
      oligo/mesohaline and hypoxic Neuse River Estuary (NRE), North Carolina, USA
      survived hypoxic exposures longer than crabs from the euhaline and normoxic Bogue
      and Back Sounds, North Carolina. Furthermore, small NRE crabs survived longer
      than large NRE crabs. Hemocyanin (Hcy) concentration did not explain these
      individual-level differences, however, hypoxia-tolerant crabs had Hcy structures
      indicative of a high-O(2)-affinity form of Hcy, suggesting Hcy "quality" (i.e.,
      structure) may be more important for hypoxia survival than Hcy "quantity" (i.e.,
      concentration). The geographic differences in survival we observed also highlight
      the importance of carefully selecting experimental animals when planning to
      extrapolate results to the population level.

PMID- 20035436
TI  - Inducible viral inoculation system with cultured plant cells facilitates a
      biochemical approach for virus-induced RNA silencing.
AB  - An inducible virus infection system was demonstrated to be an efficient protein
      expression system for inducing synchronous virus vector multiplication in
      suspension-cultured plant cells. A GFP-tagged tomato mosaic virus (ToMV-GFP)
      derivative that has a defect in its 130 K protein, a silencing suppressor of
      ToMV, was synchronously infected to tobacco BY2 cultured cells using this system.
      In the infection-induced cells, viral RNA was degraded rapidly, and a cytosol
      extract prepared from the infected cells showed RNA degradation activity specific
      for ToMV- or GFP-related sequences. In lysate prepared from cells infected by
      ToMV-GFP carrying the wild-type 130 K protein, sequence-specific RNA degradation
      activity was suppressed, although siRNA derived from the virus was generated.
      Furthermore, the 130 K protein interfered with 3'-end methylation of siRNA. The
      inducible virus infection system may provide a method for biochemical analysis of
      antiviral RNA silencing and silencing suppression by ToMV.

PMID- 20035437
TI  - Genetic structure and putative selective sweep in the pioneer tree, Zanthoxylum
      ailanthoides.
AB  - Zanthoxylum ailanthoides Siebold & Zucc. is one of the most frequently
      encountered pioneer trees in Japanese warm-temperate evergreen oak forests. Our
      previous study in one region of Japan suggested high levels of population
      differentiation and putative natural selection acting on one of the nuclear loci
      analyzed. Here, we extend our analysis to study the genetic structure of 10
      populations of Z. ailanthoides across Japan using 9 simple sequence repeat (SSR)
      loci for a better understanding of its genetic structure. First, the southernmost
      population (Kagoshima) in the samples was found to have the highest genetic
      diversity, suggesting there was a glacial refugium at or near the location of the
      population. Second, relatively strong genetic differentiation was found among
      populations, and there was a positive correlation between genetic distances and
      geographic distances (Mantel test; P < 0.001). Based on this information, we
      analyzed nucleotide variation at the putatively selected locus homologous to the
      gene encoding the ADP-glucose pyrophosphorylase large subunit (agpL). Despite the
      strong genetic differentiation among populations suggested by the SSR loci, the
      agpL locus was monomorphic in almost all populations analyzed. The results of
      this study strongly supported the possibility of a selective sweep at or near the
      agpL locus.

PMID- 20035438
TI  - Pattern electroretinogram optimized for glaucoma screening (PERGLA) and retinal
      nerve fiber thickness in suspected glaucoma and ocular hypertension.
AB  - The purpose of this study is to evaluate pattern electroretinogram optimized for
      glaucoma screening (PERGLA) and retinal nerve fiber layer (RNFL) at spectral
      optical coherence tomography (OCT) in eyes with suspected glaucoma (GS) and in
      eyes with ocular hypertension (OHT). This is a cross-sectional, observational
      study. Twenty-four patients with GS (BCVA 20/20, normal visual field, intraocular
      pressure, IOP, less than 21 mmHg, and glaucomatous optic neuropathy, GON) and 14
      patients with OHT (BCVA 20/20, intraocular pressure 25 mmHg, absence of
      glaucomatous optic neuropathy and normal visual field) were considered in this
      study. GON was intended as vertical cup-disk ratio of 0.5 or more; asymmetry of
      greater than 0.2, disk notching, disk splinter hemorrhages. PERGLA amplitude and
      phase were measured, while thickness of the RNFL was obtained with spectral OCT.
      A control group of 50 age-matched healthy patients was added. In the GS group, 16
      eyes (66.7%) showed normal average RNFL analysis and normal PERGLA, 3 eyes
      (12.5%) showed abnormal average RNFL analysis and abnormal PERGLA, 5 eyes (20.8%)
      presented with normal average RNFL analysis and abnormal PERGLA. In the OHT
      group, 11 eyes (78.6%) showed an average normal RNFL and normal PERGLA, while 3
      eyes (21.4%) presented with an average normal RNFL and abnormal PERGLA. PERGLA is
      a non-invasive, fast, and fully automatic version of the pattern ERG. In eyes
      with OHT and in eyes with GS, PERGLA abnormalities in presence of a normal RNFL
      could suggest an early functional damage of viable retinal ganglion cells.

PMID- 20035441
TI  - Foreword.

PMID- 20035440
TI  - The Victorian Gambling Screen: reliability and validation in a clinical
      population.
AB  - There is a need to establish reliability and the various forms of validity in all
      measures in order to feel confident in the use of such tools across a wide
      diversity of settings. The aim of this study is to describe the reliability and
      validity of the Victorian Gambling Screen (VGS) and in particular one of the sub
      scales (Harm to Self-HS) in a specialist problem gambling treatment service in
      Adelaide, Australia. Sixty-seven consecutive gamblers were assessed using a
      previously validated clinical interview and the VGS (Ben-Tovim et al., The
      Victorian Gambling Screen: project report. Victorian Research Panel, Melbourne,
      2001). The internal consistency of the combined VGS scales had a Cronbach's alpha
      of .85 with the HS scale .89. There was satisfactory evidence of convergent
      validity which included moderate correlations with another measure of gambling
      the South Oaks Gambling Screen. There were also moderate correlations with other
      measures of psychopathology. Finally, how the VGS may best be used in clinical
      settings is discussed.

PMID- 20035439
TI  - Role of nutritional zinc in the prevention of osteoporosis.
AB  - Zinc is known as an essential nutritional factor in the growth of the human and
      animals. Bone growth retardation is a common finding in various conditions
      associated with dietary zinc deficiency. Bone zinc content has been shown to
      decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting
      its role in bone disorder. Zinc has been demonstrated to have a stimulatory
      effect on osteoblastic bone formation and mineralization; the metal directly
      activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational
      process of protein synthesis, in the cells, and it stimulates cellular protein
      synthesis. Zinc has been shown to stimulate gene expression of the transcription
      factors runt-related transcription factor 2 (Runx2) that is related to
      differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit
      osteoclastic bone resorption due to inhibiting osteoclast-like cell formation
      from bone marrow cells and stimulating apoptotic cell death of mature
      osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear
      factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter
      has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is
      involved in transcription. The intake of dietary zinc causes an increase in bone
      mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is
      chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone
      formation is more intensive than that of zinc sulfate. Zinc acexamate has also
      been shown to have a potent-anabolic effect on bone. The oral administration of
      AHZ or zinc acexamate has the restorative effect on bone loss under various
      pathophysiologic conditions including aging, skeletal unloading, aluminum bone
      toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen
      deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new
      supplementation factor in the prevention and therapy of osteoporosis.

PMID- 20035443
TI  - Corals have already evolved the vertebrate-type hormone system in the sexual
      reproduction.
AB  - Most broadcast spawning scleractinian corals synchronously release gametes during
      a brief annual spawning period. In southern Taiwan, the mass spawning of
      scleractinians occurs in lunar mid-March. Endocrine system has been proposed to
      play important roles in this annual phenomenon. A scleractinian coral, Euphyllia
      ancora has been selected as a model for the hormones and reproduction studies. We
      detected the presence of estradiol (E2), testosterone (T), glucuronided E2,
      glucuronided T, aromatase, immunoreactive (ir)GnRH in coral polyps E. ancora.
      Annual profiles of sex steroids, aromatase, and irGnRH have also been
      characterized. We found the parallel increases in irGnRH concentrations,
      aromatase activity and free E2 and glucuronided E2 concentrations at the time of
      coral mass spawning. The stimulation of mammalian (m)GnRH agonist in the
      increased aromatase activity and sex steroid concentrations was also observed in
      corals. Coral extracts (irGnRH) and mGnRH agonist had a similar dose-dependent
      effect on luteinizing hormone release in black porgy fish pituitary cells (in
      vitro). In conclusion, our data suggest that irGnRH and glucuronided E2 may play
      important roles in the control of reproduction and mass spawning in corals.
      Corals already evolved the vertebrate-type hormone system in the sexual
      reproduction.

PMID- 20035442
TI  - Molecular mechanisms of sex determination and gonadal sex differentiation in
      fish.
AB  - We have used various genetic and molecular approaches to investigate the
      mechanisms of sex determination and gonadal sex differentiation in fish. DMY was
      identified as the sex-determining gene of medaka. In tilapia, endogenous
      estrogens act as natural inducers of ovarian differentiation, while DMRT1 may be
      important for testicular differentiation. The roles of these regulators in sex
      determination and gonadal sex differentiation were ascertained using a gene or
      hormonal blockade strategy.

PMID- 20035444
TI  - Sex change in coral reef fish.
AB  - Gonadal differentiation can take many forms in fish, ranging from gonochorism,
      where individuals directly develop as male or female and finally possess only
      testis or ovaries at sexual maturation, to hermaphroditism where the same
      individuals can produce mature male and female gametes at some time in their
      lives. Hermaphrodite fish are, thus, an excellent model for studying the
      plasticity of sex determination and differentiation in vertebrates. We have shown
      that sex steroids play a principal role in sex differentiation and sex change in
      fish. Our laboratory implements several fish models that undergo sex change from
      female to male or male to female or in both directions. In this review, we will
      briefly discuss recent advances in our understanding of the mechanism of sex
      change in coral reef fish.

PMID- 20035445
TI  - Promoter analysis of two aromatase genes in the serial-sex changing gobiid fish,
      Trimma okinawae.
AB  - Despite numerous endocrine studies on sex change in teleost, no general mechanism
      that mediates sex change has emerged. The gobiid fish, Trimma okinawae, can
      change sex in both directions repeatedly. This phenomenon of sex change in goby
      assigns it as an excellent animal model to elucidate the understanding mechanisms
      of sex change. In hermaphrodite fishes, estrogen plays a particularly important
      role in natural and experimentally induced sex change. To investigate the role of
      estrogen in the serial-sex changing fish T. okinawae, we cloned and analyzed the
      5'-flanking regions of P450arom genes from goby genome DNA. Both regions have
      consensus sequences of TATA, CRE and ERE. Ad4 binding site was restricted in the
      region of P450aromA. These findings indicate that different regulators control
      the expression of the two P450arom genes.

PMID- 20035446
TI  - Ontogenic expression patterns of several nuclear receptors and cytochrome P450
      aromatases in brain and gonads of the Nile tilapia Oreochromis niloticus suggests
      their involvement in sex differentiation.
AB  - Using semi-quantitative reverse transcriptase polymerase chain reaction we
      analyzed the ontogenic expression patterns of several nuclear receptors (estrogen
      receptors [ERalpha and beta], androgen receptors [ARalpha and beta], Ad4BP/SF-1
      and Dax-1) and cytochrome P450 aromatases (brain and ovarian types) in whole
      brain and gonads of the Nile tilapia. ERalpha and beta transcripts were evident
      in both sexes with a high expression of ERalpha in females at 0 day after
      hatching (0 dah). ARalpha appeared early (0 dah) in males and while in females at
      25 dah. Among the two types of cytochrome P450 aromatases, the expression of the
      brain type (bP450arom) but not the ovarian type (oP450arom) was evident from 0 to
      90 dah in the whole brain of both males and females. Expression of Ad4BP/SF-1 in
      female brain began from 0 dah but in male brain at 5 dah. Expression of Dax-1
      began at 0 dah and it was higher throughout in male brain than that of the female
      brain. In gonads, ERalpha and beta transcripts were evident in both sexes with
      slight variation. In females, both oP450arom and Ad4BP/SF-1 amplicons were
      evident at 15 dah. In males, although faint expressions of Ad4BP/SF-1 amplicons
      were evident at early duration of development, oP450arom did not appear until 90
      dah. Conversely, expression of bP450arom was observed throughout in the
      developing testis with varied pattern while in developing ovary it was evident
      till 15 dah and reappeared only after 90 dah. Taken together, present results
      suggest that brain acts merely as a synchronizer in the sex differentiation
      process initiated by gonadal cues/factors in the Nile tilapia.

PMID- 20035447
TI  - Isolation, cloning, sequencing of brain type aromatase and its expression in male
      and female Wrasse, Pseudolabrus sieboldi.
AB  - Pseudolabrus sieboldi, wrasse being a diurnal spawner provides a good opportunity
      to study the endocrine mechanism of estrogen formation in brain and gonads.
      Moreover, an extremely large amount of E2 was produced in serum and testis of
      wrasse. It is assumed that the presence of E2 may play a major role in diurnal
      gametogenesis in male fish. In this study brain type aromatase have been
      isolated, cloned and sequenced from the brain of wrasse. Further, the expression
      pattern of brain type aromatase in gonads and adult tissue of male and female
      fish have been analyzed. In addition, the diurnal expression pattern of brain
      type aromatase in both male and female fish brain during spawning season have
      been analyzed.The P450arom (br) was isolated, cloned and sequenced from both male
      and female bamboleaf wrasse. The P450arom (br) gene (1877 sequenced nucleotide)
      contains an ORF of 1470 bp, a 5'-UTR of 18 bp and at least 407 bp in 3'-UTR. The
      amino acid sequence homology in the coding region of wrasse P450arom (br) is high
      compared to that of medaka, Oryzias latipes (80%), rainbow trout type 2,
      Oncorhynchu mykiss (78.2%), fugu, Takifugu ribripes (78%) rainbow trout type 1,
      (76%), goldfish, Carassius auratus (66.8%) and zebrafish, Danio rerio (66.2%).
      Expression study reveals that P450arom (br) mRNA were most abundant in brains of
      both male and female fish throughout the day during the spawning season. RT-PCR
      study revealed that P450arom (br) was expressed in skin, anal fin and tail fin of
      both male and female wrasse. P450arom (br) was not detected at any time of the
      spawning day in either ovary or testis of wrasse.

PMID- 20035448
TI  - Effect of methyl testosterone- and ethynyl estradiol-induced sex differentiation
      on catfish, Clarias gariepinus: expression profiles of DMRT1, Cytochrome
      P450aromatases and 3 beta-hydroxysteroid dehydrogenase.
AB  - The objective of the present study is to observe the effect of exogenous
      steroids, methyl testosterone (MT) and ethynyl estradiol (EEL) on gonadal
      differentiation and analyze its effect on the expression of several genes during
      testicular and ovarian differentiation in juvenile catfish. Exogenous hormone
      treatments (MT and EEL) were given by immersion at different days of hatching.
      The histological analysis revealed that the EEL- and MT-treatments resulted in
      the initiation of ovarian and testicular differentiation, respectively. This is
      further supported by specific expression of two forms of DMRT1 in the MT-treated
      group but not in the EEL-treated group at 47 days after hatching (dah). The
      reverse is true for the expression of ovarian aromatase. Results of the semi
      quantitative RT-PCR show that brain aromatase transcript levels are high in 47
      dah control (histologically female) and 47 dah EEL-treated fish, as compared to
      47 dah MT-treated fish. At 60 dah, brain aromatase showed elevation in its
      expression. Interestingly, the expression pattern of 3 beta-HSD did not show any
      change in EEL- and MT-treated fish. The present study also provides a strategy to
      study sex differentiation, for those species where genetic sex population is
      unavailable.

PMID- 20035449
TI  - Isolation of dopamine D(2) receptor (D (2)R) promoters in Mugil cephalus.
AB  - This paper reports the isolation of two putative D(2)R promoters from grey
      mullet, one 5'flanking and the other an intronic sequence immediately upstream of
      the first coding exon. Promoter activity of the intronic sequence was confirmed
      in vitro through functional analysis using luciferase as reporter gene. The
      functional characteristics of the region flanking the 5'UTR is currently under
      investigation.

PMID- 20035450
TI  - GnRH and gpcr: laser-captured single cell gene profiling.
AB  - We have developed a novel single cell real-time quantitative PCR technique, which
      incorporates harvesting marker-identified single cells using laser-capture. Here,
      for the first time in a vertebrate species, using this innovative single cell
      gene profiling technique, we report the presence of G-protein coupled receptors
      in individual gonadotropin-releasing hormone (GnRH) neurons and endocrine cells
      of the pituitary of the tilapia Oreochromis niloticus. The differential
      expression of multiple combinations of three GnRH receptor types (R1, R2 and R3)
      in individual gonadotropic and nongonadotropic cells demonstrates cellular and
      functional heterogeneity. The differential use of GnRH receptors in
      corticotropes, melanotropes and thyrotropes during gonadal maturation and
      reproductive behaviors suggests new roles for these hormones. Further, we provide
      evidence of the structure of a novel nonmammalian G-protein coupled receptor
      (GPR54) for kisspeptins, encoded by Kiss-1 gene, which is highly conserved during
      evolution and expressed in GnRH1, GnRH2 and GnRH3 neurons. We hypothesize GPR54
      stimulates GnRH secretion and is crucial for pubertal maturation. We speculate,
      the use of this method will allow the identification and quantification of known
      and unknown genes in single cells, which would greatly facilitate our
      understanding of the complex interactions that govern the physiology of
      individual cells in vertebrates species.

PMID- 20035451
TI  - Seabream GnRH: partial cDNA cloning, localization and stage-dependent expression
      in the ovary of snake head murrel, Channa striatus.
AB  - Vertebrate reproduction is under the neuroendocrine control of the hypothalamic
      decapeptide GnRH which synchronizes various reproductive events and influences
      other reproduction related aspects like spawning behavior and pheromonal action
      in fish. Multiple forms of GnRH peptides have been reported across diverse
      vertebrate and invertebrate classes. Here we report the partial seabream GnRH
      (sbGnRH) cDNA sequence cloned from the brain of Channa striatus (snake head
      murrel) a fresh water perciform with immense economic and medicinal value across
      Asiatic countries. sbGnRH mRNA was found in brain, gill and ovary of mature
      murrel with possible implications to the effect of GnRH on pheromonal phenomena
      and on reinitiation of oocyte meiosis. In keeping with the earlier reported role
      of GnRH in initiation of oocyte meiosis we here present evidence from RT-PCR, ICC
      demonstrating an increase in the level of sbGnRH mRNA in ovary from pre
      vitellogenic to post-vitellogenic follicles.

PMID- 20035452
TI  - Reproduction phase-related variations in the GnRH immunoreactive fibers in the
      pineal of the Indian major carp Cirrhinus mrigala (Ham.).
AB  - We studied GnRH immunoreactivity in the pineal gland of the Indian major carp
      Cirrhinus mrigala during different phases of reproductive cycle. In the resting
      phase (December-January), GnRH immunoreactive (-ir) fibers were organized as
      paired fascicles above the posterior commissure that ascend in the stalk and
      distribute widely in the pineal gland. The GnRH-ir fiber density significantly
      declined (P<0.001) during the preparatory phase (February-April) and the fibers
      disappeared thereafter. While no GnRH fibers were seen during the prespawning
      (May-June) and spawning (July-August), isolated GnRH-ir fibers reappeared in the
      postspawning phase. Since no GnRH cell bodies were detected in the pineal, these
      GnRH-ir fibers seem to be of central origin. The results reveal a distinct
      reciprocal relationship between the GnRH immunoreactivity in the pineal and the
      status of the ovarian maturity; the fibers appeared in the pineal only during the
      period of ovarian quiescence. While the functional significance of these cyclic
      changes in GnRH is yet to be determined, we suggest that the decapeptide may
      serve as a transmitter of central origin that modulates the activity of the
      pineal gland.

PMID- 20035453
TI  - Role of neuropeptide Y (NPY) in the regulation of reproduction: study based on
      catfish model.
AB  - Significance of NPY in the regulation of GnRH-LH axis was evaluated. Considerable
      NPY immunoreactivity was seen in the components like olfactory system, basal
      telencephalon, preoptic and tuberal areas, and the pituitary gland that serve as
      neuroanatomical substrates for processing reproductive information. Close
      anatomical association as well as colocalizations of NPY and GnRH were seen in
      the olfactory receptor neurons, olfactory nerve fibers and their terminals in the
      glomeruli, ganglion cells of nervus terminalis, medial olfactory tracts, fibers
      in the ventral telencephalon and pituitary. In the pituitary, NPY fibers seem to
      innervate the GnRH as well as LH cells. Intracranial administration of NPY
      resulted in significant increase in the GnRH immunoreactivity in all the
      components of the olfactory system. In the pituitary, NPY augmented the
      population of GnRH fibers and LH cells. HPLC analysis showed that salmon GnRH
      content in the olfactory organ, bulb, preoptic area+telencephalon and pituitary
      was also significantly increased following NPY treatment. NPY may play a role in
      positive regulation of GnRH throughout the neuraxis and also up-regulate the LH
      cells in the pituitary.

PMID- 20035454
TI  - Glucagon-like peptide-1 (GLP-1) immunoreactivity in the forebrain and pituitary
      of the teleost, Clarias batrachus (Linn.).
AB  - Glucagon-like peptide-1-immunoreactivity (GLP-ir) was seen in several olfactory
      receptor neurons in the olfactory epithelium and in the olfactory nerve fascicles
      that extend caudally to the bulb and innervate the glomerular layer. Thick GLP-ir
      fascicles were seen in the medial olfactory tracts (MOT); these probably
      represent the extrabulbar olfactory projections. GLP-ir fibers in the MOT
      penetrate into the telencephalon, swing dorsocaudally into the area ventralis
      telencephali/pars supracommissuralis (Vs) just above the anterior commissure. The
      immunoreactive fascicles continue caudally in the dorsal hypothalamus and are
      traceable as far as the lateral recesses. Scattered GLP-ir fibers were seen in
      the ventral telencephalon and preoptic area. While several immunoreactive cells
      were seen in the pars intermedia of the pituitary gland, few were encountered in
      the rostral pars distalis and proximal pars distalis. Role for the peptide in the
      processing of olfactory information and in the regulation of pituitary gland may
      be suggested.

PMID- 20035455
TI  - Immunocytochemical localization of gonadotropins during the development of XX and
      XY Nile tilapia.
AB  - Gonadal development and steroidogenesis in teleosts is regulated by two
      gonadotropic hormones; luteinizing hormone (LH) and follicle-stimulating hormone
      (FSH). Earlier studies in tilapia have shown that FSH-beta and LH-beta appear by
      14 days after hatching (dah), results from the current study corroborate with
      these previous reports in tilapia. Here we demonstrate the appearance of LH in
      pituitary between 14 and 20 dah. In addition to this the present study primarily
      focuses on any possible differences in appearance of LH-beta and FSH-beta
      immunoreactivity between XX and XY population of Nile tilapia. LH
      immunoreactivity was found to be lower in pituitary of XX fish when compared to
      XY fish. The development of FSH-beta immunoreactivity in pituitary of the Nile
      tilapia is also presented. Overall, it remains to be established what
      significance these findings on the appearance of gonadotropins hold for sex
      differentiation in tilapia.

PMID- 20035456
TI  - Seasonal dynamics in gonadotropin secretion and E(2)-binding in the catfish
      Heteropneustes fossilis.
AB  - In the present investigation, significant annual/seasonal variations were noticed
      in plasma and pituitary gonadotropin (GTH) which were correlated with gonado
      somatic index, plasma estradiol-17beta, and nuclear E(2) receptor (NE(2)R) in the
      pituitary, hypothalamus and telencephalon. The NE(2)R concentrations and
      dissociation constant (k (d)) values showed significant seasonal variations with
      high values in the late preparatory phase and low values in the postspawning
      phase. The NE(2)R levels were the highest in the pituitary, followed by the
      hypothalamus and telencephalon in all the seasons. In the prespawning phase,
      ovariectomy (OVX) elicited a strong negative feedback on GTH secretion with a
      bimodal pattern of release and elevated the NE(2)R levels and k (d) values,
      without producing any significant change in the resting phase suggesting that
      E(2) appears to exert differential feedbacks on GTH secretion.

PMID- 20035457
TI  - Effect of thyroid hormone depletion on monoamines and expression patterns of
      catfish GnRH in the air-breathing catfish, Clarias gariepinus.
AB  - Thyroid hormone is known to have profound effect on the efficient functioning of
      the reproductive system. The GnRH-gondaotropin (GTH) axis is the crucial axis
      involved in regulation of the various aspects of reproduction like
      spermatogenesis, synthesis of sex steroids and regulation of courting and
      spawning behavior. Earlier study from our laboratory has shown that thyroid
      hormone depletion causes a decrease in GTH and GnRH levels in pituitary and
      preoptic area, respectively. GnRH secretion in pre-optic area is largely
      regulated by the monoaminergic system mainly dopamine (DA), epinephrine (E),
      norepinephrine (NE) and serotonin (5-HT). The expression pattern of catfish GnRH
      transcripts tends to corroborate our earlier findings. Hence, in the current
      study we aimed to investigate the levels of monoamines in the preoptic area
      hypothalamus (POA-H), so as to determine whether thyroid hormone depletion
      modulates the monoaminergic neurotransmission thereby affecting GnRH secretion.
      The levels of NE and L-dopa decreased significantly while that of DA was
      unaltered following thyroid hormone depletion. DA has an inhibitory effect on
      GnRH secretion. Findings from the present study suggest that the inhibitory tone
      is unaltered while the stimulatory tone influencing GnRH neurons in POA-H is
      decreased during thiourea induced thyroid hormone depletion.

PMID- 20035458
TI  - The first success of glass eel production in the world: basic biology on fish
      reproduction advances new applied technology in aquaculture.
AB  - The eel has long been esteemed as an important food fish in the world, especially
      in Japan, and has been used as an experimental fish for many fields of fish
      physiology. However, the decreases in eel resources have been a serious concern
      in recent years. The catches of glass eels as seedlings for aquaculture have
      shown a long-term decrease in both Europe and East Asia. To increase eel
      resources, the development of techniques for artificial induction of maturation
      and spawning and rearing their larvae have been eagerly desired. Recent progress
      of reproductive physiology of fish, especially mechanisms of oocyte maturation
      and ovulation in female and of spermatozoa maturation in male, facilitate to
      establish techniques for hormonal induction of maturation and spawning in
      sexually immature eels. With persistent effort to development of rearing
      techniques of larvae, we have first succeeded to produce glass eel. These applied
      techniques are may contribute to understand the basic reproductive physiology of
      the eel.

PMID- 20035459
TI  - Implication of melatonin in oocyte maturation in Indian major carp Catla catla.
AB  - Importance of melatonin (N-acetyl-5-methoxytryptamine) in the regulation of
      oocyte maturation has been studied in a carp Catla catla. Melatonin secretory
      cells were immunocytochemically localized only in the end vesicle. Diurnal and
      seasonal studies indicated that the serum levels of melatonin exhibit a minimum
      diurnal value in the mid-day of all seasons, but the peak value is attained
      either at mid-night or just before the onset of light. Moreover, highest seasonal
      value of melatonin was noted in the post-spawning phase. Administration of
      melatonin at different doses (25, 50, or 100 mug/100 g body weight) for 1, 15, or
      30 days resulted in either pro- or anti-gonadal effects depending on the
      reproductive seasons. In vitro study revealed that incubation of oocytes with
      melatonin 4h prior to addition of MIH in the medium led to an accelerated rate of
      oocyte maturation through the formation of a complex of two proteins (MPF),
      cyclin B and cyclin dependant kinase, Cdc2. Moreover, melatonin pre-incubation
      considerably increased MIH stimulation of histone H1 phosphorylation as compared
      to MIH alone. Taken together, gathered information promotes the idea of a
      physiological role of melatonin in the maturation of oocytes in Catla catla.

PMID- 20035460
TI  - Gonadotropins and their paracrine signaling network in the zebrafish ovary.
AB  - Pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing
      hormone (LH), play fundamental roles in vertebrate ovarian development and
      function. However, there has been an increasing body of evidence that the actions
      of FSH and LH are mediated or modulated by a variety of locally produced peptide
      or protein factors, which form an intimate regulatory network within and between
      the ovarian follicles. In the past few years, a variety of growth factors have
      been identified and characterized in the zebrafish ovary including activin and
      epidermal growth factor (EGF), which are important components of the intraovarian
      communication network. To understand how this local network interacts with the
      gonadotropins from the pituitary, we have recently cloned and characterized all
      the subunits of zebrafish FSH and LH from the pituitary as well as their
      receptors (FSHR and LHR) from the ovary. Using the Chinese hamster ovary (CHO)
      cells as the bioreactor, we have produced recombinant zebrafish FSH and LH with
      biological activities. With the recombinant hormones available, the functions of
      zebrafish FSH and LH in the ovary and their interactions with the local factors
      will be an important issue to address in the future. This review briefly
      summarizes some recent work from our laboratory and others on both gonadotropins
      and their potential intraovarian signaling factors in the zebrafish.

PMID- 20035462
TI  - Expression of 20beta-hydroxysteroid dehydrogenase and P450 17alpha
      hydroxylase/c17-20 lyase during hCG-induced in vitro oocyte maturation in snake
      head murrel Channa striatus.
AB  - Partial cDNAs encoding carbonyl reductase like 20beta-hydroxysteroid
      dehydrogenase (20beta-HSD) and P450 17alpha-hydroxylase/c17-20 lyase (CYP17) were
      isolated from the ovary of snake head murrel and they exhibited high sequence
      identity to the Nile tilapia and rainbow trout, respectively. A low transcript
      level of both 20beta-HSD and CYP17 were detected in pre-vitellogenic follicles,
      while the transcript level was high in full-grown immature follicles. In hCG
      induced in vitro oocyte maturation, we found a significant increase in 20beta-HSD
      transcript level after 2 h. The CYP17 transcripts also showed a considerable
      increase following hCG-induction compared to saline-treated controls. On the
      other hand, Western blot analysis demonstrated no significant change in the CYP17
      protein level during hCG-induced in vitro oocyte maturation. Taken together, we
      suggest that in addition to 20beta-HSD, the CYP17 might have a role in the shift
      in steroidogenesis during meiotic maturation of snake head murrel.

PMID- 20035463
TI  - Effect of piscine GH/IGF-I on final oocyte maturation in vitro in Heteropneustes
      fossilis.
AB  - Growth hormone (GH) has recently been identified as co-gonadotropin regulating
      fish reproduction, hitherto, no effort has been made to see its effect on oocyte
      maturation in fishes, though some reports demonstrate the role of insulin like
      growth factor-I (IGF-I) in oocyte maturation in teleosts. Hence, effect of GH on
      oocyte maturation in post-vitellogenic H. fossilis has been worked out in the
      present study. Post-vitellogenic follicles in the ovarian tissue were challenged
      in vitro with H. fossilis pituitary homogenate (fPH), Clarias batrachus GH and
      GtH, barramundi IGF-I (IGF-I), 17alpha, 20beta-dihydroxy-4-pregnen-3-one (DHP)
      and testosterone alone, or in combination with IGF-I for 18 h at 26+/-1 degrees
      C. Incubation of ovarian tissue with GH in the presence of actinomycin D: or
      cycloheximide or barramundi IGF-I antiserum was also made separately. In general,
      oocyte maturation was induced by fPH, barramundi IGF-I, GtH, GH and DHP, which
      was augmented further by addition of barramundi IGF-I. Testosterone had no effect
      on GVBD. Actinomycin D: , cycloheximide and anti barramundi IGF-I abolished the
      GH induced oocyte maturation. Present study suggests for the first time that GH
      has a role in egg maturation in fish.

PMID- 20035461
TI  - Aromatase distribution and regulation in fish.
AB  - Cytochrome P450 aromatase is the enzyme complex responsible for the synthesis of
      estrogens by the aromatization of androgens. In the vast majority of tetrapods
      examined so far, aromatase is the product of the Cyp19 gene, which exists as a
      single copy per haploid genome. In contrast, in teleosts there are two isoforms
      of the aromatase gene, Cyp19a and Cyp19b, which encode two structurally different
      proteins, P450aromA and P450aromB, respectively, with similar catalytic
      activities. The promoter region of both genes has been characterized in several
      teleost species and more than 20 different regulatory sites have been identified
      to date. These include response elements for members of the nuclear receptor
      superfamily, notably sex steroid receptors, and at least five transcription
      factors related to neurogenesis. This supports the idea that, besides other
      functions such as the control of reproduction, aromatase and therefore estrogens
      are actively involved in neurogenesis. Aromatase mRNA expression studies revealed
      that P450aromA and P450aromB are preferentially, but not exclusively, expressed
      in the gonads and brain, respectively. Other organs and tissues where aromatase
      is expressed, albeit at much lower levels include the pituitary, retina, anterior
      kidney, testis, liver and visceral fat, suggesting local actions of estrogens in
      several peripheral targets. Gene expression levels are usually matched by actual
      catalytic activity, with K (m) usually in the range 5-50 nM and V (max) in the
      order of a few pmol/mg protein/h. The current challenge is to understand the
      regulation of both aromatase genes, especially in the context of sex
      differentiation and as a response to environmental factors, including
      temperature, social interactions, and endocrine disruptors, which is briefly
      reviewed. It is also important to gain a better understanding of the specific
      functions of estrogen in different tissues and key developmental and reproductive
      events throughout the fish life.

PMID- 20035464
TI  - Purification of vitellogenin from the air breathing catfish, Clarias gariepinus.
AB  - Vitellogenin (Vtg) is a female specific glycophospholipoprotein which can be
      induced both in male and female with estradiol and xeno-estrogens. The basic
      theme behind the purification of vitellogenin from the fish is to understand the
      evolutionary relationship and for the purification and characterization of the
      Vtg receptor. The male catfish, Clarias gariepinus was administrated with
      estradiol over a period of time for the synthesis of Vtg and the serum was
      collected. The Vtg was purified from the serum using a two step chromatographic
      technique. The serum was passed on to DEAE-ion exchange column and the protein
      was eluted using a salt gradient. The fractions containing the Vtg were pooled
      and passed onto a gel permeation chromatography column and the pure protein was
      obtained. The molecular weight is around 200 kDa on the SDS-PAGE and around 520
      kDa on the native gel electrophoresis.

PMID- 20035465
TI  - In vitro induction of vitellogenin by estradiol 17 beta in isolated hepatocytes
      of catfish, Clarias gariepinus.
AB  - Vitellogenin is a female-specific calcium-binding glycolipophosphoprotein
      synthesized in the hepatocytes of fishes. Its synthesis can be induced in fishes
      of either sex by estradiol or by xenoestrogens. To study the in vitro synthesis
      of vitellogenin, different culture conditions were set up using the hepatocytes
      of Clarias gariepinus. The present study reports on a non-enzymatic procedure for
      isolation and culture of hepatocytes from the liver of the catfish Clarias
      gariepinus, in order to study the effects of estradiol on vitellogenin synthesis
      in vitro. The procedure employs chelating properties of ethylenediamine
      tetracetic acid to achieve cell viability in excess of 95%. Equal numbers of
      isolated cells were incubated in different culture media viz. RPMI F1640, Medium
      199, and Williams' Medium E. At 36 h, cell attachment and monolayer formation is
      faster in M-199 and Williams' Medium E than in RPMI. In order to study the
      effects of estradiol on vitellogenin synthesis, the isolated hepatocytes were
      seeded in Williams' Medium E in 24-well cell culture plates. 17 beta-estradiol
      (E(2)) was introduced in the culture plates at different concentrations and for
      different time periods. The media were assayed for vitellogenin using competitive
      ELISA. Vitellogenin appeared in the medium after 48 h of incubation with 10(-5) M
      estradiol whereas after 72 h of incubation 5x10(-7) M E(2) could elicit the
      synthesis.

PMID- 20035466
TI  - Selective ligand-binding determinants in catfish and human gonadotropin
      receptors.
AB  - In mammals, the specificity of FSH-FSH receptor (FSHR), LH-LH receptor (LHR) and
      TSH-TSH receptor couples is such that no cross-activation occurs under normal
      physiological conditions. The interactions between fish gonadotropins and their
      receptors, however, appear to be less discriminatory. For example, the catfish
      FSHR is highly responsive to both catfish LH and catfish FSH, while the catfish
      LHR is specific for its cognate LH. Comparative structure-function studies aimed
      at elucidating the molecular basis of ligand promiscuity (in fish) and ligand
      selectivity (in mammals) are described in this paper.

PMID- 20035467
TI  - Molecular cloning, gene expression and characterization of the third estrogen
      receptor of the Nile tilapia, Oreochromis niloticus.
AB  - Estrogens are essential for many reproductive and non-reproductive functions. In
      teleosts, it is well-known that several subtypes of estrogen receptors are
      required for the precise action of estrogens. Present study describes the cloning
      of the third estrogen receptor, ER- beta2, from the Nile tilapia by EST
      sequencing coupled microarray. The cloned ER-beta2 showed 77.7% amino acid
      identity with the reported Atlantic croaker ER-beta. Three ERs, ER-alpha, ER
      beta1 and ER-beta2, from the fugu genome were also isolated to analyze their gene
      structures. Comparison of the intron/exon boundaries and exon numbers of fugu,
      tilapia, rainbow trout and zebrafish, and phylogenetic analysis of 63 ER
      sequences revealed that ER-beta probably underwent two successive lineage
      specific duplications in teleost. The former took place only in zebrafish
      lineage, and the latter took place in advanced teleosts without the zebrafish
      lineage, whereas no duplication of the ER-alpha gene has been detected. Tissue
      distribution analysis by RT-PCR revealed that tilapia ER-alpha and ER-beta1 were
      expressed ubiquitously, whereas ER-beta2 is expressed only in the pituitary,
      liver, intestine, kidney and gonads, with the highest expression in the testis
      and the lowest level in the ovary. Northern blot analysis detected a single
      transcript of about 3.4 kb in the testis but not in the ovary mRNAs. In transient
      transfection assays using human embryonic kidney 293 (HEK293) cells, tilapia ER
      beta2 showed estrodiol-17beta dependent transactivation.

PMID- 20035468
TI  - Thyroid hormone modulation of ovarian recrudescence of air-breathing catfish
      Clarias gariepinus.
AB  - In the present study, thiourea-induced thyroid hormone depletion and thyroxine
      (T(4)) 'overdose' were used as a strategy to understand the influence of thyroid
      hormones on ovarian recrudescence of juvenile (3-months-old), immature (8-months
      old) and adult (1-year-old) air-breathing catfish, Clarias gariepinus. Thiourea
      induced thyroid hormone depletion in juvenile catfish impaired ovarian
      development, but no significant effect was observed in immature catfish and
      during late stage of ovarian recrudescence of mature catfish. T(4) treatment in
      females undergoing late stages of ovarian recrudescence induced rapid oocyte
      growth by promoting its early entry into maturational phase as evident from the
      presence of more number of vitellogenic and post-vitellogenic follicles, decrease
      in aromatse immunoreactivity and reduced estradiol-17beta levels. Hence, thyroid
      hormones have an important role to play during early stages of ovarian
      development and vitellogenesis of catfish and also indicating that thyroid has a
      stage dependent effect on ovary.

PMID- 20035469
TI  - Thyroxine-induced alterations in the testis and seminal vesicles of air-breathing
      catfish, Clarias gariepinus.
AB  - Effect of experimentally induced thyroxine overdose on the testis and seminal
      vesicles was studied in the air-breathing catfish, Clarias gariepinus during the
      preparatory and the pre-spawning phase. The present study revealed a marked
      reduction in testosterone level in serum, testis and seminal vesicles (SV).
      Histological examination showed a considerable reduction in the number of
      spermatozoa/spermatids in the seminiferous tubular lumen as well as depletion of
      fluid in the loculi of SV. SDS-PAGE analysis of SV fluid proteins demonstrated a
      significant decrease in the level of a ~27 kDa protein in thyroxine treated
      fishes. Evidences are presented here to indicate that thyroid hormone plays a
      role in regulating testis and SV function in catfish.

PMID- 20035470
TI  - Thiourea-induced alteration in the expression patterns of some steroidogenic
      enzymes in the air-breathing catfish Clarias gariepinus.
AB  - Previous study from our laboratory on thiourea-induced thyroid hormone depletion
      in mature male catfish demonstrated that thyroid hormones play a significant role
      in testicular function. In the present study, we aimed to analyze the changes in
      the expression pattern of several steroidogenic enzyme genes after thyroid
      hormone depletion using semi quantitative RT-PCR in both adult male and female
      catfish. There was a marked decrease in the 11beta-hydroxylase expression in the
      testis and liver while no change was observed in case of kidney. A significant
      decrease in 11beta-hydroxysteroid dehydrogenase transcript level in testis, liver
      and kidney were observed in the thiourea treated males. The results obtained
      corroborated with our earlier findings of testicular regression after thyroid
      hormone depletion. In females, expression of aromatase transcript increased in
      experimental group compared to control. There was no considerable change observed
      in the transcript level of 3beta-hydroxysteroid dehydrogenase, P450 17alpha
      hydroxylase/C17-20-lyase, and 20beta-hydroxysteroid dehydrogenase in both males
      and females. Thus, thyroid hormones might exert modulating effect on
      steroidogenic enzyme genes at the transcription level.

PMID- 20035471
TI  - Transgene integration - an analysis in autotransgenic Labeo rohita Hamilton
      (Pisces: Cyprinidae).
AB  - Transgenic Labeo rohita founder population was analyzed for the presence of
      autotransgene having histone 3 promoter and growth hormone (GH) cDNA (LRH3
      GHcDNA) or total GH gene (LRH3-GH2.8) by PCR with transgene specific primers.
      Transgene specific amplification was seen with LRH3-GHcDNA in five out of seven
      individuals and all three fishes with LRH3-GH2.8, indicating their transgenic
      nature. Transgene integration was also studied by Southern hybridization of DNA
      isolated from blood of the transgenic fishes with two different probes (histone 3
      promoter and cDNA of L. rohita). Autotransgene integration was confirmed in all
      PCR positive transgenic individuals. The site of integration of the transgene in
      the genome of the four transgenic fish could be determined by inverse PCR. Two
      individuals showed integration at the same site whereas in the remaining two
      individuals the integration sites were different.

PMID- 20035472
TI  - Immunological and physiological validation of enzyme-linked immunosorbent assay
      for growth hormone of the Asian catfish, Clarias batrachus.
AB  - This study describes the development and validation of competitive antigen
      capture enzyme-linked immunosorbent assay (ELISA) for growth hormone (GH) of the
      catfish, Clarias batrachus. Isolated GH was characterized first through bioassay,
      amino acid sequencing, immunoblotting and immunocytochemistry, and then used to
      raise antibody to develop ELISA. The lowest detection limit of the assay system
      was 0.17 ng ml(-1), and the standard curve had an ED(50) value of 0.35 ng ml(-1).
      Repeated determination of GH in a plasma pool exhibited intra- and interassay co
      efficient of variation of 8.1% and 7.09% (n=5), respectively. Dose-response
      inhibition curves resulting from dilutions of plasma and pituitary homogenate of
      C. batrachus were parallel to the standard curve, while such parallelism in the
      case of Cyprinus carpio and H. fossilis was absent revealing no cross reaction of
      them in the present ELISA. In vivo effects of sGnRH, testosterone, 5-HT and
      morphine on plasma GH were also examined to validate the ELISA physiologically.
      sGnRH, testosterone and morphine increased, while 5-HT decreased GH level in a
      dose-dependent manner.

PMID- 20035473
TI  - Identification of a novel gill-specific calpain from rainbow trout (Oncorhynchus
      mykiss).
AB  - Calpains are calcium-dependent neutral proteases responsible for many cellular
      functions. The two forms of calpain ubiquitously expressed in mammalian tissues
      are known as mu-calpain and m-calpain. We report here the identification of a
      novel calpain that is similar to but distinct from the mu- and m-calpains in
      rainbow trout. The cDNA of the novel gene is 2623 bp in length with a single open
      reading frame. The predicted protein (676 amino acids) contains the conserved
      calpain characteristic domains that include: domain I (pro peptide), II (cysteine
      catalytic site), III (electrostatic switch), and IV (calmodulin-like) with five
      Ca(2+)-binding EF hands. Northern blot and RT-PCR analyses demonstrated that the
      novel calpain gene is predominantly expressed in rainbow trout gills. Comparison
      of the novel protein with the ubiquitously expressed calpains and several
      mammalian tissue-specific calpains revealed that the novel calpain is an
      orthologue of the mammalian digestive tract specific calpain (calpain 9).

PMID- 20035474
TI  - Different expressions of trypsin and chymotrypsin in relation to growth in
      Atlantic salmon (Salmo salar L.).
AB  - The expressions of trypsin and chymotrypsin in the pyloric caeca of Atlantic
      salmon (Salmo salar L.) were studied in three experiments. Two internal (trypsin
      phenotypes, life stages) and three common external factors (starvation, feeding,
      temperatures) influencing growth rates were varied. Growth was stimulated by
      increased temperature and higher feeding rate, and it was depressed during
      starvation. The interaction between trypsin phenotype and start-feeding
      temperature affected specific activity of trypsin, but not of chymotrypsin.
      Trypsin specific activity and the activity ratio of trypsin to chymotrypsin (T/C
      ratio) increased when growth was promoted. Chymotrypsin specific activity, on the
      other hand, increased when there was a reduction in growth rate whereas fish with
      higher growth had higher chymotrypsin specific activity resulting in lower T/C
      ratio value. During a rapid growth phase, trypsin specific activity did not
      correlate with chymotrypsin specific activity. On the other hand, a relationship
      between specific activities of trypsin and chymotrypsin could be observed when
      growth declined, such as during food deprivation. Trypsin is the sensitive key
      protease under conditions favouring growth and genetically and environmentally
      affected, while chymotrypsin plays a major role when growth is limited or
      depressed. Trypsin specific activity and the T/C ratio value are shown to be
      important factors in the digestion process affecting growth rate, and could be
      applicable as indicators for growth studies of fish in captive cultures and in
      the wild, especially when food consumption rate cannot be measured.

PMID- 20035475
TI  - Effects of aromatizable and nonaromatizable androgens on the sex inversion of red
      spotted grouper (Epinephelus akaara).
AB  - The effects of aromatizable 17alpha-methyltestosterone (MT) and non-aromatizable
      17alpha-methyldihydrotestosterone (MDHT) on sex inversion in red-spotted grouper,
      Epinephelus akaara, were investigated. Fish were implanted with MT, MDHT and
      MT+AI (aromatase inhibitor, AI) respectively for one month. The results showed
      that the three treated groups turned into transitional stage with intersex
      gonads, which contained atretic oocytes and spermatogenic germ cells at all
      stages of spermatogenesis. The controls did not change sex. The gonads of more
      than half MT-implanted fish were in early transitional stages of sex inversion,
      whereas those of more than half MDHT and MT+AI-implanted fish were in late
      transitional stages of sex inversion. No difference in serum estradiol-17beta
      (E(2)) levels between the controls and the treated groups were observed, whereas
      11-ketotestosterone (11-KT) and testosterone (T) levels increased in all treated
      groups. Significantly lower gonadosomatic index (GSI) and gonadal aromatase
      activity were observed in the treated groups, which were in accordance with the
      lower mRNA expression of P450aromA. However, P450aromB mRNA expression increased
      in the MT group, while it did not change in the MDHT group. These results suggest
      that the sex inversion of red-spotted grouper by MT and MDHT implantation might
      be due to the suppression of P450aromA gene expression, and resulting in both the
      decrease of the ovarian estrogen -secretion, as well as the increase in the 11-KT
      levels. Furthermore, the main reason for MT being less effective than MDHT might
      be due to partial aromatization of MT to estrogen.

PMID- 20035476
TI  - Purification and characterization of hatching enzyme from flounder Paralichthys
      olivaceus.
AB  - Using chorion of Paralichthys as a specific substrate, hatching enzyme (HE) from
      Paralichthys olivaceus (PHE) was purified by gel-filtration and ion-exchange
      chromatography, and characterized in terms of its molecular weight and enzymatic
      properties in this study. It was found that the molecular size of PHE is about
      34.8 kDa in SDS-PAGE. The PHE had obvious choriolytic activity, which was optimal
      at pH 7.0 and temperature of 35 degrees C, respectively. The Km value of the PHE
      for casein was 4.28 mg ml(-). The PHE was very sensitive to trypsin-specific
      inhibitors, especially serine protease-specific inhibitors, such as LBTI, SBTI,
      bestatin and p-APMSF, leupeptin, ovomucoid, PMSF, pepstatin A and TLCK, indicates
      that it is a trypsin-type serine protease. The PHE was also extremely sensitive
      to Cu(2+) and Ca(2+), combined with the results that it was inhibited by EDTA in
      a dose-dependent manner, indicates this PHE is also a kind of metalloprotease.

PMID- 20035477
TI  - Serum biochemical parameters of Acipenser persicus.
AB  - Serum biochemical parameters are important aspects in the management of
      endangered species, such as Acipenser persicus. The values of these parameters
      can be used for confirming the maturity and for monitoring any changes in the
      quality of waters and related soils. Serum samples of 44 A. persicus fishes were
      analyzed and their serum parameter values were determined as Mean+/-SD in four
      groups: mature males and females and immature males and females, respectively. We
      compared the levels of calcium (Ca; 1.97 +/- 0.31-2.38 +/- 0.28 mmol/l), blood
      urea nitrogen (BUN; 4.4 +/- 0.54-6.16 +/- 0.63 mmol/l), cholesterol (CHO; 2.55 +/
      0.42-13.51 +/- 0.65 mmol/l), creatinine (CREA; 27.23 +/- 3.5-83.98 +/- 7.5
      mmol/l), magnesium (Mg; 2.74 +/- 0.18-3.05 +/- 0.46 mmol/l), bilirubin
      (Bilirubin; 2.05 +/- 0.42-13.93 +/- 4.39 mumol/l), aspatate transaminase (AST;
      18.25 +/- 1.5-167 +/- 38 Iu/l), alanine transaminase (ALT; 11 +/- 1-25.33 +/-
      9.24 Iu/l), alkaline phosphatase (ALP; 183.5 +/- 17.68-523 +/- 66.23 Iu/l) and
      creatine kinase (CK; 157.5 +/- 27.58-2132.2 +/- 250.92 Iu/l). We have shown that
      there were no differences in the Ca and Mg levels among the different groups.
      However, mature females have higher CREA, AST, CHO and lower BUN, ALP and ALT
      than the immature females. In the mature males, the values of ALP and bilirubin
      were higher yet the values of CREA and ALT were lower than in the immature males.

PMID- 20035478
TI  - Acute toxicity of nitrite on tilapia (Oreochromis niloticus) at different
      external chloride concentrations.
AB  - Tilapias (Oreochromis niloticus) juveniles (total length 4.9 +/- 0.2 cm and
      weight 1.8 +/- 0.2 g) were exposed to several nitrite concentrations (0, 10, 18,
      32, 56 and 100 mg l(-1)) for 96 h, using a semi-static renewal method at chloride
      levels of 35.0 and 70.0 mg l(-1). At the end of the 96-h period, the median
      lethal concentration (LC(50)) of nitrite was 28.18 mg l(-1) in water with low
      chloride content (35.0 mg l(-1)) and 44.67 mg l(-1) with high chloride content
      (70.0 mg l(-1), respectively). It indicated that high concentrations of chloride
      ions could reduce the toxicity of nitrite. During the toxicity experiments, the
      behaviour and clinical signs of tilapias were also observed. Furthermore, the
      test of toxic mechanism was designed taking five test concentrations, viz., 5,
      10, 15 and 20 mg l(-1) and a nitrite-free control. Nitrite exposure produced high
      levels of methaemoglobin (MHb) but did not seem to cause mortality, as surviving
      tilapias showed high levels (85.37 +/- 2.23 and 53.82 +/- 3.44 at 35.0 and 70.0
      mg l(-1) chloride, respectively). The percentage of MHb exposed to nitrite was
      significantly higher (P<0.05) than the control (0 mg l(-1) nitrite) and increased
      with the increasing nitrite concentration. However, the percentage of MHb
      decreased with the increasing chloride concentration.

PMID- 20035479
TI  - Distribution of different taste buds and expression of alpha-gustducin in the
      barbells of yellow catfish (Pelteobagrus fulvidraco).
AB  - In order to explore the distribution of different taste buds in the barbells of
      yellow catfish (Pelteobagrus fulvidraco) collected from the Yangtze River, the
      quantity, morphology and distribution of different taste buds in the barbells was
      studied by bright-field optical microscope and scanning electron microscopy. The
      taste buds in the barbell were predominantly localized at the middle two thirds
      regions of the barbells, and could be categorized into three major types based on
      their morphological and histological features. Type I and II TB were distributed
      on the elevated layer of the surrounding epithelium, while Type III TB ended
      apically at the level with the epithelium. Significant quantitative differences
      (p < 0.05) in the TB number within unit length barbell were observed between NB
      and MB (p = 0.00001), NB and MIB (p = 0.00758), and NB and MOB (p = 0.00209); no
      significant differences (p > 0.05) were found between MB and MIB (p = 0.05293),
      MB and MOB (p = 0.05994) and MIB and MOB (p = 0.08320). The number, distribution
      and morphological variability of TBs could be a consequence of adaptation to the
      environment. alpha-Gustducin immunofluoresence signals were detected in cells of
      all types of TBs. The strong expression of alpha-gustducin on the barbells of
      catfish suggests that the taste-induced signal transduction in taste cells was
      common to all vertebrates.

PMID- 20035480
TI  - Comparative blood biochemistry of Amur sturgeon, Acipenser schrenckii, and
      Chinese surgeon, Acipenser sinensis.
AB  - This study compared Amur sturgeon (Acipenser schrenckii) and Chinese sturgeon
      (Acipenser sinensis) on several biochemical parameters including glucose (GLU),
      urea, lactate dehydrogenase (LDH-L), activities of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), direct bilirubin (D.BILI), alkaline
      phosphatase (ALP), cholesterol (CHOL), triglyceride (TGL), creatinine (CREA),
      total protein (TP), and total bilirubin (T.BILI). The results showed that there
      were great differences in these parameters between the two species. The
      concentrations of GLU, UREA, LDH-L, ALT, AST, D.BILI, ALP, CHOL, TGL, CREA, and
      T.P for the Amur sturgeon were significantly higher than those for Chinese
      sturgeon.The T.BILI level of the Amur sturgeon was, however, significantly lower
      than that for the Chinese sturgeon.

PMID- 20035481
TI  - Standard oxygen consumption of seasonally acclimatized cownose rays, Rhinoptera
      bonasus (Mitchill 1815), in the northern Gulf of Mexico.
AB  - Standard oxygen consumption rate (MO(2)) was determined for 19 cownose rays
      (Rhinoptera bonasus) using flow-through respirometry. Rays ranged in size from
      0.4 to 8.25 kg (350-790 mm DW). Respirometry experiments were conducted on
      seasonally acclimatized rays at temperatures from 19.0 to 28.8 degrees C.
      Estimates of mass-dependent MO(2) ranged from 55.88 mg O(2) kg(-1) h(-1) for an
      8.25 kg ray to 332.75 mg O(2) kg(-1) h(-1) for a 2.2 kg animal at 22-25 degrees
      C. Multiple regression analysis examining the effect of temperature, salinity,
      and mass on standard mass-independent MO(2) found temperature (P < 0.01), and
      mass (P < 0.0001) to have a significant effect on oxygen consumption, whereas
      salinity did not (P > 0.05). Q (10) was calculated as 2.33 (19-28 degrees C),
      falling between the estimates determined for two other batoid species, the bull
      ray (Myliobatos aquila; Q (10) = 1.87) and the bat ray (Myliobatis californica; Q
      (10) = 3.00). The difference in the Q (10) estimates may be attributed to the use
      of seasonally acclimatized as opposed to laboratory-acclimated animals.

PMID- 20035482
TI  - Alterations in enzyme activities in vital organs of triploid female catfish
      Heteropneustes fossilis (Bloch).
AB  - Triploid Heteropneustes fossilis (Bloch) showed sterility and higher growth
      potential than the normal diploid fish. Activities of some metabolic enzymes such
      as cytosolic NADP-malate dehydrogenase (NADP-MDH), mitochondrial NAD-malate
      dehydrogenase (NAD-MDH) and glutamate pyruvate transaminase (GPT) were evaluated
      in liver, brain and kidney along with glucose-6-phosphate dehydrogenase (G-6-P D)
      in ovary of female triploid catfish. Activities of these enzymes showed distinct
      seasonal periodicity, mostly with highest activities in prespawning and spawning
      periods, in both diploid and triploid catfish but differed in magnitude. In
      triploid liver, GPT showed higher activity than the diploid counterpart in
      prespawning and spawning periods. On the contrary, mitochondrial NAD-MDH and
      cytosolic NADP-MDH in this organ showed a consistent lower activity than the
      diploid in all stages or in some stages of reproductive cycle respectively.
      Interestingly, none of the enzymes in brain and kidney of triploid female catfish
      showed significant changes in comparison to the diploid counterpart. The triploid
      ovary maintained a significantly lower level of G-6-P D activity throughout the
      resting, preparatory and pre-spawning periods compared to the diploid ovary.
      Lower level of malic enzymes (NAD-MDH and NADP-MDH) in liver and G-6-P D in ovary
      are in close synchrony with lower level of estradiol-17beta in plasma of female
      triploids as found in earlier study.

PMID- 20035483
TI  - Molecular cloning and sequencing of hemoglobin-beta gene of channel catfish,
      Ictalurus punctatus Rafinesque.
AB  - The hemoglobin-beta gene of channel catfish, Ictalurus punctatus, was cloned and
      sequenced. Total RNA from head kidneys was isolated, reverse transcribed and
      amplified. The sequence of the channel catfish hemoglobin-beta gene consists of
      600 nucleotides. Analysis of the nucleotide sequence reveals one open reading
      frame and 5'- as well as 3'-untranslated regions. The open reading frame of the
      sequence potentially encodes 148 amino acids with a calculated molecular mass of
      16.3 kDa. The pI and charge at pH 7.0 of the deduced hemoglobin-beta protein were
      7.28 and 0.47, respectively. Overall, 22 amino acid residues were conserved
      throughout the sequences, including His64 and His93, the sites for heme-binding.
      Unlike the counterpart of other common cultured fish such as Salmo salar,
      Oncorhynchus nerka, Oncorhynchus mykiss, Cyprinus carpio and Ctenopharyngodon
      idella, the hemoglobin-beta of channel catfish did not have cysteine. The amino
      acid sequence of channel catfish hemoglobin-beta shows 84% homology with that of
      Silurus asotus (both are in the order Siluriformes). However, comparison with
      those of other fish species shows homology ranging from 53 to 68%. Structural
      analysis by the 3D-PSSM program displays that channel catfish hemoglobin-beta has
      eight alpha-helices, A-H.

PMID- 20035484
TI  - Effects of malathion and cadmium on acetylcholinesterase activity and
      metallothionein levels in the fish Seriola dumerilli.
AB  - The potential use of acetylcholinesterase (AChE) and metallothionein (MT)
      responses as biomarker of organophosphorous (OPs) and trace metal were assessed
      in fish Seriola dumerilli exposed to 0, 4, 6 mg/kg of malathion for 2, 7 and 13
      days, and to 0, 50, 100, 250 mug/kg of Cd for 2 days. Brain AChE was
      significantly inhibited after 2 and 7 days of malathion exposure, in a dose
      response manner, but no inhibition was observed after 13 days of exposure. When
      exposed to Cd for 2 days, S. dumerelli presented an increase in AChE activity at
      a concentration of 50 mug/kg, but a strong and dose-dependent AChE inhibition at
      100 and 250 mug/kg. Cd treatment also caused a rapid increase in MTs
      concentration in liver, even at the lower concentration. Our experiments indicate
      that the measurement of hepatic MT concentration and brain AChE activity in S.
      dumerilli would be useful biomarkers of OP and Cd exposure and/or effects.

PMID- 20035490
TI  - Psychological stress in sports coaches: a review of concepts, research, and
      practice.
AB  - Sports coaches operate within a complex, ever-changing environment that imposes
      many pressures on them. Here, we address the psychological impact of these
      demands via a critical review of the literature pertaining to stress in sport
      coaches. The narrative is divided into three main sections: (1) conceptual and
      definitional issues, (2) theoretical and empirical issues, and (3) implications
      for applied practice. The review focuses on the environmental stressors that
      coaches encounter, their appraisals of and responses to these demands, and the
      impact this has on their personal well-being and job performance. The influence
      of various personal and situational characteristics is also discussed. A key
      message to emerge from this review is that the potential health and performance
      costs of psychological stress to sports coaches are significant. The rapid rate
      of change in contemporary sport and the dynamic nature of stress mean that stress
      in coaches is an ongoing problem that needs to be monitored and addressed.

PMID- 20035486
TI  - Gangrenous cheilitis associated with all-trans retinoic acid therapy for acute
      promyelocytic leukemia.
AB  - A 67-year-old Japanese woman who presented with erythema on the abdomen and
      pancytopenia was found to have acute promyelocytic leukemia (APL). A skin biopsy
      revealed invasion of APL cells. She was started on induction treatment with all
      trans retinoic acid (ATRA) at 45 mg/m(2). On day 4, the leukemic cell number had
      increased to over 1.0 x 10(9)/L. Consequently, chemotherapy with idarubicin and
      cytarabine was initiated. On day 10, dryness of the lips appeared. The lower lip
      swelled and developed painful black eschars. A high fever was also present.
      Despite discontinuing ATRA on day 20 and administering antibiotics, an anti
      fungal agent and valaciclovir, these signs did not improve. Histopathologically,
      the biopsied lip revealed infiltration of neutrophils and vasculitis. The patient
      was given ATRA on days 29 and 30 due to an increase in APL cell numbers, after
      which the gangrenous cheilitis extended over the whole lip. On day 49, the
      patient was started on re-induction treatment with arsenic trioxide. She achieved
      complete remission and the gangrenous cheilitis slowly healed over the following
      8 weeks. Since the clinical features of the gangrenous cheilitis in this case
      were similar to those of ATRA-associated scrotal ulcers, it appears that
      activated neutrophils derived from differentiated APL cells may have caused the
      gangrenous cheilitis. Physicians should be alert to the development of gangrenous
      cheilitis during treatment with ATRA.

PMID- 20035485
TI  - High dietary fat exacerbates weight gain and obesity in female liver fatty acid
      binding protein gene-ablated mice.
AB  - Since liver fatty acid binding protein (L-FABP) facilitates uptake/oxidation of
      long-chain fatty acids in cultured transfected cells and primary hepatocytes,
      loss of L-FABP was expected to exacerbate weight gain and/or obesity in response
      to high dietary fat. Male and female wild-type (WT) and L-FABP gene-ablated mice,
      pair-fed a defined isocaloric control or high fat diet for 12 weeks, consumed
      equal amounts of food by weight and kcal. Male WT mice gained weight faster than
      their female WT counterparts regardless of diet. L-FABP gene ablation enhanced
      weight gain more in female than male mice-an effect exacerbated by high fat diet.
      Dual emission X-ray absorptiometry revealed high-fat fed male and female WT mice
      gained mostly fat tissue mass (FTM). L-FABP gene ablation increased FTM in
      female, but not male, mice-an effect also exacerbated by high fat diet.
      Concomitantly, L-FABP gene ablation decreased serum beta-hydroxybutyrate in male
      and female mice fed the control diet and, even more so, on the high-fat diet.
      Thus, L-FABP gene ablation decreased fat oxidation and sensitized all mice to
      weight gain as whole body FTM and LTM-with the most gain observed in FTM of
      control vs high-fat fed female L-FABP null mice. Taken together, these results
      indicate loss of L-FABP exacerbates weight gain and/or obesity in response to
      high dietary fat.

PMID- 20035491
TI  - Objectively measured daily physical activity related to aerobic fitness in young
      children.
AB  - The purpose of this study was to investigate by direct measurement the cross
      sectional relationship between accelerometer-measured physical activity and peak
      oxygen uptake (VO(2peak): ml x min(-1) x kg(-1)), in a population-based cohort of
      young children, since such data are scarce. The study included 468 children (246
      boys, 222 girls) aged 6.7 + or - 0.4 years, recruited from a population-based
      cohort. Peak oxygen uptake was measured by indirect calorimetry during a maximal
      treadmill exercise test. Physical activity was assessed by accelerometers over a
      4-day period. Minutes of sedentary, light, moderate, moderate-to-vigorous, and
      vigorous activity per day were calculated. Mean counts per minute were considered
      to reflect total physical activity. Pearson correlation coefficients indicated a
      weak relationship between daily physical activity variables and VO(2peak) in boys
      (r = 0.15-0.28, P < 0.05), with the exception of time in sedentary and light
      activity, which was not related to VO(2peak). None of the daily physical activity
      variables were related to VO(2peak) in girls, with the exception of a very weak
      relationship for moderate activity (r = 0.14, P < 0.05). Multiple regression
      analyses indicated that the various physical activity variables explained between
      2 and 8% of the variance in VO(2peak) in boys. In this population-based cohort,
      most daily activity variables were positively related to aerobic fitness in boys,
      whereas less clear relationships were observed in girls. Our finding that
      physical activity was only uniformly related to aerobic fitness in boys partly
      contradicts previous studies in older children and adolescents.

PMID- 20035492
TI  - Rapid weight loss followed by recovery time does not affect judo-related
      performance.
AB  - In this study, we investigated the effects of rapid weight loss followed by a 4-h
      recovery on judo-related performance. Seven weight-cycler athletes were assigned
      to a weight loss group (5% body weight reduction by self-selected regime) and
      seven non-weight-cyclers to a control group (no weight reduction). Body
      composition, performance, glucose, and lactate were assessed before and after
      weight reduction (5-7 days apart; control group kept weight stable). The weight
      loss group had 4 h to re-feed and rehydrate after the weigh-in. Food intake was
      recorded during the weight loss period and recovery after the weigh-in.
      Performance was evaluated through a specific judo exercise, followed by a 5-min
      judo combat and by three bouts of the Wingate test. Both groups significantly
      improved performance after the weight loss period. No interaction effects were
      observed. The energy and macronutrient intake of the weight loss group were
      significantly lower than for the control group. The weight loss group consumed
      large amounts of food and carbohydrate during the 4-h recovery period. No changes
      were observed in lactate concentration, but a significant decrease in glucose
      during rest was observed in the weight loss group. In conclusion, rapid weight
      loss did not affect judo-related performance in experienced weight-cyclers when
      the athletes had 4 h to recover. These results should not be extrapolated to
      inexperienced weight-cyclers.

PMID- 20035493
TI  - Effects of the addition of a resistance training programme to a caloric
      restriction weight loss intervention on psychosocial factors in overweight and
      obese post-menopausal women: a Montreal Ottawa New Emerging Team study.
AB  - The aim of this study was to examine the effects of the addition of a resistance
      training programme to a caloric restriction weight loss intervention on
      psychosocial profile. The study sample consisted of 137 overweight and obese post
      menopausal women. Participants were randomized to a caloric restriction group and
      caloric restriction + resistance training group. Psychosocial, anthropometric,
      and metabolic variables were measured before and after the 6-month weight loss
      intervention. Both groups presented similar weight loss and there were no
      significant differences between the caloric restriction group and caloric
      restriction + resistance training group for changes in psychosocial profile.
      Thereafter, all participants were classified into quintiles based on the amount
      of weight loss. In all quintiles, women markedly improved body esteem and self
      esteem, and decreased hunger and perceived risk for diabetes mellitus (P < 0.05).
      However, significant increases in dietary restraint were observed in quintiles 2
      5 (> or =2.4 % body weight loss), decreases in disinhibition in quintiles 3-5 (>
      or =4.9 %), increases in self-efficacy in quintiles 3-5 (> or =4.9 %), and
      increases in health perceptions in quintile 5 (> or =11.1%). The results of this
      study do not support the hypothesis that the addition of a resistance training
      programme to a caloric restriction weight loss intervention has additional
      benefits on psychosocial profile. Overall, the significant improvements in the
      psychosocial profile observed were mostly accounted for by the degree of weight
      loss.

PMID- 20035494
TI  - Optimization of insulin-mediated creatine retention during creatine feeding in
      humans.
AB  - The aim of this study was to determine whether creatine ingested in combination
      with relatively small quantities of essential amino acids, simple sugars, and
      protein would stimulate insulin release and augment whole-body creatine retention
      to the same extent as a large bolus of simple sugars. Seven young, healthy males
      underwent three randomized, 3-day experimental trials. Each day, 24-h urine
      collections were made, and on the second day participants received 5 g creatine +
      water (creatine trial), 5 g creatine + approximately 95 g dextrose (creatine +
      carbohydrate) or 5 g creatine + 14 g protein hydrolysate, 7 g leucine, 7 g
      phenylalanine, and 57 g dextrose (creatine + protein, amino acids, and
      carbohydrate) via naso-gastric tube at three equally spaced intervals. Blood
      samples were collected at predetermined intervals after the first and third naso
      gastric bolus. After administration of the first and third bolus, serum insulin
      concentration was increased by 15 min (P < 0.05) in the creatine + carbohydrate
      and creatine + protein, amino acids, and carbohydrate trials compared with
      creatine alone, and plasma creatine increased more following creatine alone (15
      min, P < 0.05) than in the creatine + carbohydrate and creatine + protein, amino
      acids, and carbohydrate trials. Urinary creatine excretion was greater with
      creatine alone (P < 0.05) than with creatine + carbohydrate and creatine +
      protein, amino acids, and carbohydrate. Administration of creatine + protein,
      amino acids, and carbohydrate can stimulate insulin release and augment whole
      body creatine retention to the same extent as when larger quantities of simple
      sugars are ingested.

PMID- 20035495
TI  - Research trainees in the clinical neurosciences: still a shallow pool.

PMID- 20035500
TI  - Gender differences in pediatric stroke: is elevated testosterone a risk factor
      for boys?

PMID- 20035501
TI  - Cardiovascular disease in epileptic patients: how to assess the clinical risk?

PMID- 20035502
TI  - Intracranial atherosclerotic disease: an update.
AB  - The consensus conference on intracranial atherosclerosis provides a comprehensive
      review of the existing literature relevant to the epidemiology, diagnosis,
      prevention, and treatment of intracranial atherosclerosis, and identifies
      principles of management and research priorities. Patients who have suffered a
      stroke or transient ischemic attack attributed to stenosis (50-99%) of a major
      intracranial artery face a 12 to 14% risk for subsequent stroke during the 2-year
      period after the initial ischemic event, despite treatment with antithrombotic
      medications. The annual risk for subsequent stroke may exceed 20% in high-risk
      groups. In patients with intracranial atherosclerotic disease, short-term and
      long-term anticoagulation is not superior to antiplatelet treatment. Overall, the
      subgroup analyses from randomized trials provide evidence about benefit of
      aggressive atherogenic risk factor management. Intracranial angioplasty with or
      without stent placement has evolved as a therapeutic option for patients with
      symptomatic intracranial atherosclerotic disease, particularly those with high
      grade stenosis with recurrent ischemic symptoms, medication failure, or both. A
      multicenter randomized trial is currently under way to compare stent placement
      with intense medical management for patients with high-grade symptomatic
      intracranial atherosclerotic disease.

PMID- 20035503
TI  - Single-cell expression profiling of dopaminergic neurons combined with
      association analysis identifies pyridoxal kinase as Parkinson's disease gene.
AB  - OBJECTIVE: The etiology of Parkinson disease (PD) is complex and multifactorial,
      with hereditary and environmental factors contributing. Monogenic forms have
      provided molecular clues to disease mechanisms but genetic modifiers of
      idiopathic PD are still to be determined. METHODS: We carried out whole-genome
      expression profiling of isolated human substantia nigra (SN) neurons from
      patients with PD vs. controls followed by association analysis of tagging single
      nucleotide polymorphisms (SNPs) in differentially regulated genes. Association
      was investigated in a German PD sample and confirmed in Italian and British
      cohorts. RESULTS: We identified four differentially expressed genes located in PD
      candidate pathways, ie, MTND2 (mitochondrial, p = 7.14 x 10(-7)), PDXK (vitamin
      B6/dopamine metabolism, p = 3.27 x 10(-6)), SRGAP3 (axon guidance, p = 5.65 x 10(
      6)), and TRAPPC4 (vesicle transport, p = 5.81 x 10(-6)). We identified a DNA
      variant (rs2010795) in PDXK associated with an increased risk of PD in the German
      cohort (p = 0.00032). This association was confirmed in the British (p = 0.028)
      and Italian (p = 0.0025) cohorts individually and reached a combined value of p =
      1.2 x 10(-7) (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.18-1.44).
      INTERPRETATION: We provide an example of how microgenomic genome-wide expression
      studies in combination with association analysis can aid to identify genetic
      modifiers in neurodegenerative disorders. The detection of a genetic variant in
      PDXK, together with evidence accumulating from clinical studies, emphasize the
      impact of vitamin B6 status and metabolism on disease risk and therapy in PD.

PMID- 20035505
TI  - NerveCenter: VA scuttles Gulf war illness single-source contract, reignites
      debate surrounding earmarking of funding for science.

PMID- 20035504
TI  - Dicer ablation in oligodendrocytes provokes neuronal impairment in mice.
AB  - OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression and have many roles in the
      brain, but a role in oligodendrocyte (OL) function has not been demonstrated.
      METHODS: A Dicer floxed conditional allele was crossed with the proteolipid
      protein promoter-driven inducible Cre allele to generate inducible, OL-specific
      Dicer-floxed mice. RESULTS: OL-specific Dicer mutants show demyelination,
      oxidative damage, inflammatory astrocytosis and microgliosis in the brain, and
      eventually neuronal degeneration and shorter lifespan. miR-219 and its target
      ELOVL7 (elongation of very long chain fatty acids protein 7) were identified as
      the main molecular components that are involved in the development of the
      phenotype in these mice. Overexpressing ELOVL7 results in lipid accumulation,
      which is suppressed by miR-219 co-overexpression. In Dicer mutant brain, excess
      lipids accumulate in myelin-rich brain regions, and the peroxisomal beta
      oxidation activity is dramatically reduced. INTERPRETATION: Postnatal Dicer
      ablation in mature OLs results in inflammatory neuronal degeneration through
      increased demyelination, lipid accumulation, and peroxisomal and oxidative
      damage, and therefore indicates that miRNAs play an essential role in the
      maintenance of lipids and redox homeostasis in mature OLs that are necessary for
      supporting axonal integrity as well as the formation of compact myelin.

PMID- 20035506
TI  - Copeptin: a novel, independent prognostic marker in patients with ischemic
      stroke.
AB  - OBJECTIVE: Early prediction of outcome in patients with ischemic stroke is
      important. Vasopressin is a stress hormone. Its production rate is mirrored in
      circulating levels of copeptin, a fragment of provasopressin. We evaluated the
      prognostic value of copeptin in acute stroke patients. METHODS: In a prospective
      observational study, copeptin was measured using a new sandwich immunoassay on
      admission in plasma of 362 consecutive patients with an acute ischemic stroke.
      The prognostic value of copeptin to predict the functional outcome (defined as a
      modified Rankin Scale score of <or=2 or >or=3), mortality within 90 days, was
      compared with the National Institutes of Health Stroke Scale score and with other
      known outcome predictors. RESULTS: Patients with an unfavorable outcomes and
      nonsurvivors had significantly increased copeptin levels on admission (p <0.0001
      and p <0.0001). Receiver operating characteristics to predict functional outcome
      and mortality demonstrated areas under the curve of copeptin of 0.73 (95%
      confidence interval [CI], 0.67-0.78) and 0.82 (95% CI, 0.76-0.89), which was
      comparable with the National Institutes of Health Stroke Scale score but superior
      to C-reactive protein and glucose (p <0.01). In multivariate logistic regression
      analysis, copeptin was an independent predictor of functional outcome and
      mortality, and improved the prognostic accuracy of the National Institutes of
      Health Stroke Scale to predict functional outcome (combined areas under the
      curve, 0.79; 95% CI, 0.74-0.84; p <0.01) and mortality (combined areas under the
      curve, 0.89; 95% CI, 0.84-0.94; p <0.01). INTERPRETATION: Copeptin is a novel,
      independent prognostic marker improving currently used risk stratification of
      stroke patients. Ann Neurol 2009;66:799-808.

PMID- 20035507
TI  - Molecularly targeted therapies for glioma.
AB  - Over the past decade, molecularly targeted therapies have been added to cytotoxic
      and antiendocrine drugs in the treatment of cancer, with the aim of targeting the
      molecular pathways that underlie the carcinogenic process and maintain the cancer
      phenotype. Success with some of these agents has suggested that identification
      and validation of drug targets is the starting point for the development of
      active, safe, and effective drugs. The main molecular targets used to develop
      anticancer drugs are cell surface receptors, signal transduction pathways, gene
      transcription targets, ubiquitin-proteasome/heat shock proteins, and tumor
      microenvironment components. Here, we review the development of the main
      molecularly targeted noncytotoxic agents studied in glioma, highlighting lessons
      derived from the development of these novel drugs and proposing new horizons for
      the clinical development of molecularly targeted therapies.

PMID- 20035508
TI  - Perfusion computed tomography in the acute phase of mild head injury: regional
      dysfunction and prognostic value.
AB  - OBJECTIVE: Traumatic brain injury is a major cause of disability and death. Most
      patients sustain a mild head injury with a subgroup that experiences disabling
      symptoms interfering with return to work. Brain imaging in the acute phase is not
      predictive of outcome, as 20% of noncontrast computed tomographic (CT) scans on
      admission is normal in patients with a suboptimal outcome. The aim of this study
      was to perform perfusion CT imaging in the acute phase of mild head injury in
      patients without intracranial abnormalities on the noncontrast CT, to assess
      whether these patients had cerebral perfusion abnormalities. Furthermore, the
      relation between perfusion CT parameters and severity of head injury and outcome
      was evaluated. METHODS: In patients with mild head injury and normal noncontrast
      CT, perfusion CT was performed directly after admission. The perfusion data were
      compared with data of 25 healthy control subjects. Outcome was determined 6
      months after injury with the extended Glasgow Coma Outcome Scale score and return
      to work. RESULTS: Seventy-six patients were included. In patients with a
      decreased Glasgow Coma Scale score, a significant decrease of cerebral blood flow
      and cerebral blood volume was detected in the frontal and occipital gray matter.
      In logistic regression analyses, decreased cerebral blood flow and cerebral blood
      volume in the frontal lobes predicted worse outcome according to the extended
      Glasgow Coma Outcome Scale score. CT perfusion parameters did not predict return
      to work. INTERPRETATION: In the acute phase of mild head injury, disturbed
      cerebral perfusion is seen in patients with normal noncontrast CT correlating
      with severity of injury and outcome.

PMID- 20035509
TI  - Stimulation of the subthalamic nucleus and impulsivity: release your horses.
AB  - OBJECTIVE: In Parkinson disease (PD) patients, deep brain stimulation (DBS) of
      the subthalamic nucleus (STN) may contribute to certain impulsive behavior during
      high-conflict decisions. A neurocomputational model of the basal ganglia has
      recently been proposed that suggests this behavioral aspect may be related to the
      role played by the STN in relaying a "hold your horses" signal intended to allow
      more time to settle on the best option. The aim of the present study was 2-fold:
      1) to extend these observations by providing evidence that the STN may influence
      and prevent the execution of any response even during low-conflict decisions; and
      2) to identify the neural correlates of this effect. METHODS: We measured
      regional cerebral blood flow during a Go/NoGo and a control (Go) task to study
      the motor improvement and response inhibition deficits associated with STN-DBS in
      patients with PD. RESULTS: Although it improved Unified Parkinson Disease Rating
      Scale motor ratings and induced a global decrease in reaction time during task
      performance, STN-DBS impaired response inhibition, as revealed by an increase in
      commission errors in NoGo trials. These behavioral effects were accompanied by
      changes in synaptic activity consisting of a reduced activation in the cortical
      networks responsible for reactive and proactive response inhibition.
      INTERPRETATION: The present results suggest that although it improves motor
      functions in PD patients, modulation of STN hyperactivity with DBS may tend at
      the same time to favor the appearance of impulsive behavior by acting on the
      gating mechanism involved in response initiation.

PMID- 20035510
TI  - Multimodal microglia imaging of fiber tracts in acute subcortical stroke.
AB  - OBJECTIVE: Case series with (11)C-PK11195 and positron emission tomography (PET)
      in stroke patients suggest that activated microglia may be detected in remote
      brain regions with fiber tract connections to the lesion site as an indicator of
      poststroke neuroinflammation. However, the specificity of these imaging findings
      remains to be demonstrated. METHODS: In a prospective controlled study, we
      measured microglia activity using (11)C-PK11195-PET along the pyramidal tract, as
      defined by diffusion tensor imaging, in 21 patients with first-time acute
      subcortical ischemia within 2 weeks of stroke. Uptake ratios (affected vs
      unaffected side) were determined for a set of standardized volumes of interest
      along the pyramidal tracts (PT). Uptake ratios from patients in whom the PT was
      affected were compared with those in whom the PT was not affected. Uptake ratios
      were related to motor deficit and lesion size according to correlation analyses.
      RESULTS: Increased uptake ratios were only found in patients in whom the PT was
      affected by stroke. In the affected hemisphere, uptake was increased at the level
      of pons, midbrain, and internal capsule, but not in the oval center. The extent
      of remote microglia activation was independent of infarct size or clinical
      measures of stroke severity. INTERPRETATION: A specific activation of microglia
      was only found in patients in whom the PT was affected by the stroke and only
      caudal (anterograde) to the lesion; no activation was found in the retrograde
      direction or in those patients in whom the PT was not affected. These findings
      were independent of infarct size and may represent changes secondary to early
      Wallerian degeneration.

PMID- 20035511
TI  - Multiple sclerosis: distribution of inflammatory cells in newly forming lesions.
AB  - OBJECTIVE: CD4 T-cell-dependent macrophage activation directed against a myelin
      or oligodendrocyte antigen is generally thought to be the mechanism causing
      myelin destruction in multiple sclerosis (MS). However, areas within expanding MS
      lesions may exhibit prominent oligodendrocyte loss and apoptosis in the absence
      of infiltrating lymphocytes. The present study was designed to further
      investigate the inflammatory profile of different regions within rapidly
      expanding MS lesions. METHODS: Twenty-six active lesions from 11 patients with
      early MS were serially sectioned and immunostained for T and B cells, plasma
      cells, ramified microglia, macrophages, monocytes, and CD209-positive dendritic
      cells. Cell counts were compared in prephagocytic, phagocytic, and immediately
      postphagocytic areas. RESULTS: Parenchymal T and B cells were largely absent in
      areas of initial oligodendrocyte loss and in areas of degenerate and dead myelin
      infiltrated by myelin phagocytes. In contrast, trailing areas of complete
      demyelination packed with lipid macrophages, and, in some lesions, regenerating
      oligodendrocytes, showed large numbers of T cells, B cells, and immunoglobulin G
      (IgG)-positive plasma cells. Lesions in 2 exceptionally early cases contained
      relatively few T and B cells, and no IgG-positive plasma cells. INTERPRETATION:
      Early loss of oligodendrocytes is a prominent feature in tissue bordering rapidly
      expanding MS lesions. Macrophage activity is largely an innate scavenging
      response to the presence of degenerate and dead myelin. Adaptive immune activity
      involving T and B cells is conspicuous chiefly in recently demyelinated tissue,
      which may show signs of oligodendrocyte regeneration. The findings suggest that
      plaque formation has some basis other than destructive cell-mediated immunity
      directed against a myelin or oligodendrocyte antigen.

PMID- 20035512
TI  - Magnetic resonance imaging-based quantitative iron mapping at 7-tesla remains to
      be elusive in multiple sclerosis.

PMID- 20035513
TI  - Three-dimensional surface maps link local atrophy and fast ripples in human
      epileptic hippocampus.
AB  - OBJECTIVES: There is compelling evidence that pathological high-frequency
      oscillations (HFOs), called fast ripples (FR, 150-500Hz), reflect abnormal
      synchronous neuronal discharges in areas responsible for seizure genesis in
      patients with mesial temporal lobe epilepsy (MTLE). It is hypothesized that
      morphological changes associated with hippocampal atrophy (HA) contribute to the
      generation of FR, yet there is limited evidence that hippocampal FR-generating
      sites correspond with local areas of atrophy. METHODS: Interictal HFOs were
      recorded from hippocampal microelectrodes in 10 patients with MTLE. Rates of FR
      and ripple discharge from each microelectrode were evaluated in relation to local
      measures of HA obtained using 3-dimensional magnetic resonance imaging (MRI)
      hippocampal modeling. RESULTS: Rates of FR discharge were 3 times higher in areas
      of significant local HA compared with rates in nonatrophic areas. Furthermore, FR
      occurrence correlated directly with the severity of damage in these local
      atrophic regions. In contrast, we found no difference in rates of ripple
      discharge between local atrophic and nonatrophic areas. INTERPRETATION: The
      proximity between local HA and microelectrode-recorded FR suggests that
      morphological changes such as neuron loss and synaptic reorganization may
      contribute to the generation of FR. Pathological HFOs, such as FR, may provide a
      reliable surrogate marker of abnormal neuronal excitability in hippocampal areas
      responsible for the generation of spontaneous seizures in patients with MTLE.
      Based on these data, it is possible that MRI-based measures of local HA could
      identify FR-generating regions, and thus provide a noninvasive means to localize
      epileptogenic regions in hippocampus.

PMID- 20035516
TI  - Clinical symptomatic de novo systemic transthyretin amyloidosis 9 years after
      domino liver transplantation.

PMID- 20035514
TI  - Autism and other neuropsychiatric symptoms are prevalent in individuals with
      MeCP2 duplication syndrome.
AB  - OBJECTIVE: There have been no objective assessments to determine whether boys
      with MECP2 duplication have autism or whether female carriers manifest
      phenotypes. This study characterizes the clinical and neuropsychiatric phenotypes
      of affected boys and carrier females. METHODS: Eight families (9 males and 9
      females) with MECP2 duplication participated. A detailed history, physical
      examination, electroencephalogram, developmental evaluation, Autism Diagnostic
      Observation Schedule, and Autism Diagnostic Interview-Revised were performed for
      each boy. Carrier females completed the Symptom Checklist-90-R, Wechsler
      Abbreviated Scale of Intelligence, Broad Autism Phenotype Questionnaire, and
      detailed medical and mental health histories. Size and gene content of each
      duplication were determined by array comparative genome hybridization. X
      chromosome inactivation patterns were analyzed using leukocyte DNA. MECP2 and
      IRAK1 RNA levels were quantified from lymphoblast cell lines, and western blots
      were performed to assess MeCP2 protein levels. RESULTS: All of the boys
      demonstrated mental retardation and autism. Poor expressive language, gaze
      avoidance, repetitive behaviors, anxiety, and atypical socialization were
      prevalent. Female carriers had psychiatric symptoms, including generalized
      anxiety, depression, and compulsions that preceded the birth of their children.
      The majority exhibited features of the broad autism phenotype and had higher
      nonverbal compared to verbal reasoning skills. INTERPRETATION: Autism is a
      defining feature of the MECP2 duplication syndrome in boys. Females manifest
      phenotypes despite 100% skewing of X-inactivation and normal MECP2 RNA levels in
      peripheral blood. Analysis of the duplication size, MECP2 and IRAK1 RNA levels,
      and MeCP2 protein levels revealed that most of the traits in affected boys are
      likely due to the genomic region spanning of MECP2 and IRAK1. The phenotypes
      observed in carrier females may be secondary to tissue-specific dosage
      alterations and require further study. Ann Neurol 2009;66:771-782.

PMID- 20035517
TI  - Use of thromboelastography PlateletMapping to monitor antithrombotic therapy in a
      patient with Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome (BCS) is the end result of a number of disease states
      resulting in hepatic venous outflow obstruction. We report a Janus kinase 2
      homozygous patient with BCS who thrombosed a transjugular intrahepatic
      portosystemic shunt (TIPS) despite treatment with warfarin (international
      normalized ratio = 3.0), aspirin, and clopidogrel. PlateletMapping (Haemonetics
      Corp.) is a novel point-of-care assay of platelet function based on
      thromboelastography (TEG) that has the ability to detect platelet inhibition (%)
      by antiplatelet therapy. Initial PlateletMapping traces showed no platelet
      inhibition by aspirin or clopidogrel but demonstrated adequate suppression of
      plasmatic coagulation. On this basis, the aspirin dose was doubled, and this
      resulted in a significant increase in platelet inhibition (45%). To further
      suppress platelet activity, the patient was started on tirofiban, a glycoprotein
      IIb/IIIa inhibitor. Repeat PlateletMapping revealed 100% inhibition of platelets
      by both pathways, and this coincided with angiographic evidence of TIPS blood
      flow. Subsequently, the patient developed bleeding from the venous access sites.
      TEG demonstrated poor underlying plasmatic coagulation with a prolonged R time of
      9.2 minutes (normal = 2-8 minutes), and the international normalized ratio was
      found to be supratherapeutic (>4). Treatment with fresh frozen plasma stopped the
      bleeding without compromising the platelet inhibition. This case demonstrates
      that increased platelet activation may contribute to the development of
      thromboses in BCS. Despite the standard dose of dual antiplatelet therapy, there
      was minimal inhibition in platelet function, and anticoagulation with warfarin
      alone was not adequate to prevent thrombotic events. PlateletMapping was used to
      assess and then optimize the antiplatelet treatment while facilitating the
      management of complications without an increased risk of thrombosis.

PMID- 20035518
TI  - Salvage cystic duct anastomosis using a magnetic compression technique for
      incomplete bile duct reconstruction in living donor liver transplantation.
AB  - In living donor liver transplantation (LDLT), bile duct reconstruction is often
      technically demanding due to the frequently anomalous anatomy of the bile duct,
      as well as the high incidence of biliary complications. A bile duct branch may
      also be accidentally left without anastomosis at the time of LDLT and found to be
      obstructed after surgery. Surgical revision for such cases is sometimes not
      feasible because of the invasiveness of the procedure. We report a case in which
      a bile duct branch was intentionally left without anastomosis and was later
      successfully anastomosed to the cystic duct stump using a magnetic compression
      anastomosis (MCA) technique. A combination of the MCA technique and cystic duct
      anastomosis is life-saving in certain situations and should be considered as the
      treatment of choice.

PMID- 20035519
TI  - Are recipients of solid organ transplantation a high-risk population for
      hepatitis E virus infection?

PMID- 20035520
TI  - A peer-based intervention to educate liver transplant candidates about living
      donor liver transplantation.
AB  - The number of liver donors has not measurably increased since 2004 and has begun
      to decrease. Although many waitlisted patients may be suitable candidates to
      receive a living donor graft, they are often reticent to discuss living donation
      with close friends and family, partly because of a lack of knowledge about donor
      health and quality of life outcomes after donation. The objective of this study
      was to test the effectiveness of an educational intervention that uses
      testimonials and self-report data from living donors in New York State. The study
      had an independent sample pretest (n = 437) and posttest (n = 338) design with
      posttest, between-subjects comparison for intervention exposure. All waitlisted
      patients at 5 liver transplant centers in New York were provided a peer-based
      educational brochure and DVD either by mail or at the clinic. The outcome
      measures were liver candidates' knowledge and self-efficacy to discuss living
      donation with family and friends. The number and proportion of individuals who
      presented to centers for living liver donation evaluation were also measured.
      Liver transplant candidates' self-efficacy to discuss living donation and their
      knowledge increased from the pretest period to the posttest period. Those exposed
      to the peer-based intervention reported significantly greater knowledge, a
      greater likelihood of discussing donation, and increased self-efficacy in
      comparison with those not exposed to the intervention. The results did not differ
      by age, length of time on the waiting list, education, or ethnicity. In
      comparison with the preintervention period, living donation increased 42%, and
      the number of individuals who presented for donation evaluation increased by 74%.

PMID- 20035521
TI  - Portal vein thrombosis and survival in patients with cirrhosis.
AB  - The effects of occlusive portal vein thrombosis (PVT) on the survival of patients
      with cirrhosis are unknown. This was a retrospective cohort study at a single
      center. The main exposure variable was the presence of occlusive PVT. The primary
      outcome measure was time-dependent mortality. A total of 3295 patients were
      analyzed, and 148 (4.5%) had PVT. Variables independently predictive of mortality
      from the time of liver transplant evaluation included age [hazard ratio (HR),
      1.02; 95% confidence interval (CI), 1.01-1.03], Model for End-Stage Liver Disease
      (MELD) score (HR, 1.10; 95% CI, 1.08-1.11), hepatitis C (HR, 1.44; 95% CI, 1.24
      1.68), and PVT (HR, 2.61; 95% CI, 1.97-3.51). Variables independently associated
      with the risk of mortality from the time of liver transplant listing included age
      (HR, 1.02; 95% CI, 1.01-1.03), transplantation (HR, 0.65; 95% CI, 0.50-0.81),
      MELD (HR, 1.08; 95% CI, 1.06-1.10), hepatitis C (HR, 1.50; 95% CI, 1.18-1.90),
      and PVT (1.99; 95% CI, 1.25-3.16). The presence of occlusive PVT at the time of
      liver transplantation was associated with an increased risk of death at 30 days
      (odds ratio, 7.39; 95% CI, 2.39-22.83). In conclusion, patients with cirrhosis
      complicated by PVT have an increased risk of death.

PMID- 20035522
TI  - Glycoprotein 130-dependent pathways in host hepatocytes are important for liver
      repopulation in mice.
AB  - Hepatocyte transplantation (HT) is still restricted by the limited amount of
      transplantable cells. Therefore, a better understanding of the mechanisms
      involved in cellular engraftment, proliferation, and in vivo selection is
      important. Here we aimed to evaluate the role of the interleukin 6 (IL
      6)/glycoprotein 130 (gp130) system for liver repopulation. Mice carrying a
      conditional hepatocyte-specific deletion of the common IL-6 signal transducer
      gp130 (gp130(Deltahepa)) were used for HT. First, we compared bone marrow
      transplantation (BMT), partial hepatectomy (PH), and retrorsine treatment of
      recipient mice to optimize the in vivo selection of transplanted hepatocytes. BMT
      combined with PH was sufficient to induce a 30-fold increase in the number of
      transplanted donor hepatocytes, whereas additional retrorsine pretreatment led to
      an up to 40-fold increase. Next, the influence of gp130 signaling in hepatocytes
      on cell selection was evaluated. Wild-type (WT) hepatocytes repopulated WT
      recipients at the same rate as gp130(Deltahepa) cells. In contrast, liver
      repopulation by transplanted cells was enhanced in gp130(Deltahepa) recipient
      mice. This was associated with higher proliferation of donor hepatocytes and
      enhanced apoptosis in gp130(Deltahepa) recipient livers. Additionally, the acute
      phase response was strongly induced after HT in WT recipients but blunted in
      gp130(Deltahepa) recipients. As a result, significantly more liver remodeling,
      evidenced by stronger hepatic stellate cell activation and collagen accumulation,
      was found in gp130(Deltahepa) mice after HT. In conclusion, the HT model
      established here can be efficiently applied to investigate cell-specific
      mechanisms in liver repopulation. Moreover, we have shown that gp130-dependent
      pathways in host hepatocytes are important for controlling liver repopulation.

PMID- 20035523
TI  - Emphysematous gastritis in a liver transplant recipient.

PMID- 20035524
TI  - Pregnancy outcomes among liver transplant recipients in the United States: a
      nationwide case-control analysis.
AB  - Liver transplant recipients and their infants may have an increased risk of
      obstetric complications. Our objective was to describe pregnancy outcomes in
      women with a prior transplant from a population-based perspective. We analyzed
      the 1993-2005 US Nationwide Inpatient Sample database to identify obstetric
      hospitalizations among transplant recipients (n = 206) and controls matched by
      age, hospital, and year (n = 4060). The effect of prior transplantation on
      maternal and fetal outcomes was evaluated with regression models with adjustments
      for patient and hospital factors, including admission to a transplant center.
      Between 1993 and 2005, 146 delivery admissions among liver transplant recipients
      were identified. Cesarean deliveries were more common among transplant recipients
      (38% versus 24%; P = 0.0001); however, this difference was not significant after
      multivariate adjustment [OR (odds ratio) = 0.87; 95% confidence interval (CI) =
      0.60-1.27]. Maternal mortality was similar among cases and controls (0% versus
      0.02%; P = 1.00), but transplant patients had higher rates of fetal mortality
      (6.3% versus 2.0%; P = 0.0006), antepartum admission (OR = 2.27; 95% CI = 1.59
      3.25), and maternal (OR = 2.63; 95% CI = 1.82-3.80) and fetal complications (OR =
      2.49; 95% CI = 1.68-3.70). Gestational hypertension (30% versus 9%; P < 0.0001)
      and postpartum hemorrhage (8% versus 3%; P = 0.009) were more common among
      transplant recipients; their infants had higher rates of prematurity (27% versus
      11%; P < 0.0001), distress (10% versus 5%; P = 0.005), and growth restriction (5%
      versus 2%; P = 0.05) but not congenital anomalies. Hospitalization in a
      transplant center ( approximately 50%) was associated with similar obstetric
      outcomes. In conclusion, although most pregnancy outcomes are favorable, liver
      transplant recipients and their infants have an increased risk of obstetric
      complications. Additional studies evaluating mechanisms aimed at reducing these
      complications are necessary.

PMID- 20035525
TI  - The cytoprotective effects of addition of activated protein C into preservation
      solution on small-for-size grafts in rats.
AB  - Small-for-size liver grafts are a serious obstacle for partial orthotopic liver
      transplantation. Activated protein C (APC), a potent anticoagulant serine
      protease, is known to have cell-protective properties due to its anti
      inflammatory and antiapoptotic activities. This study was designed to examine the
      cytoprotective effects of a preservation solution containing APC on small-for
      size liver grafts, with special attention paid to ischemia-reperfusion injury and
      shear stress in rats. APC exerted cytoprotective effects, as evidenced by (1)
      increased 7-day graft survival; (2) decreased initial portal pressure and
      improved hepatic microcirculation; (3) decreased levels of aminotransferase and
      improved histological features of hepatic ischemia-reperfusion injury; (4)
      suppressed infiltration of neutrophils and monocytes/macrophages; (5) reduced
      hepatic expression of tumor necrosis factor alpha and interleukin 6; (6)
      decreased serum levels of hyaluronic acid, which indicated attenuation of
      sinusoidal endothelial cell injury; (7) increased hepatic levels of nitric oxide
      via up-regulated hepatic endothelial nitric oxide synthesis expression together
      with down-regulated hepatic inducible nitric oxide synthase expression; (8)
      decreased hepatic levels of endothelin 1; and (9) reduced hepatocellular
      apoptosis by down-regulated caspase-8 and caspase-3 activities. These results
      suggest that a preservation solution containing APC is a potential novel and safe
      product for small-for-size liver transplantation, alleviating graft injury via
      anti-inflammatory and antiapoptotic effects and vasorelaxing conditions.

PMID- 20035526
TI  - Sexual functioning in long-term survivors of Hodgkin's lymphoma.
AB  - OBJECTIVE: Studies of Hodgkin's lymphoma (HL) survivors have reported long-term
      adjustment problems including sexual dysfunction, but the prevalence and
      persistence of sexual problems in HL survivors have not been well characterized.
      This study aimed to address these questions by comparing sexual health in a large
      cohort of long-term HL survivors with a noncancer control group. METHODS: A
      mailed survey including questions about current sexual problems and sexual
      satisfaction was completed by 465 HL survivors and 205 sibling controls.
      Survivors ranged from 20 to 82 years (median=44) and were treated >=7 years prior
      (median=18). RESULTS: Sexual problems were commonly reported by HL survivors,
      with 54.2% reporting decreased sexual activity and 41.4% reporting decreased
      interest. When survivors' current sexual functioning was compared with the
      control group, however, no differences were found, and overall sexual
      satisfaction was positive in both groups. Among survivors, age was not associated
      with sexual problems but had a small significant negative association with
      satisfaction (rho=-0.12; p<0.05). No associations between time since diagnosis,
      disease stage, and chemotherapy treatment and sexual functioning were found.
      CONCLUSIONS: Consistent with previous studies, HL survivors reported high rates
      of current sexual problems. However, no differences in sexual problems or sexual
      satisfaction were found between survivors and controls. Results indicate that
      over the long term, survivors' sexual functioning does not differ from noncancer
      controls. Findings underscore the importance of including healthy control groups
      to determine whether difficulties reported by cancer survivors can be attributed
      to cancer treatment.

PMID- 20035528
TI  - Longitudinal study on pediatric dyslipidemia in population-based claims database.
AB  - PURPOSE: To examine the rate of lipid testing among children from a large US
      medical insurance claims database, describe the characteristics of pediatric
      dyslipidemia, and assess the sensitivity of the International Classification of
      Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes for identifying
      dyslipidemic children. METHODS: This retrospective cohort study used the claims
      data from the Integrated Healthcare Information Services (IHCIS), for the years
      2003-2006. Two study cohorts consisted of children with laboratory-defined and
      diagnosis/treatment-defined dyslipidemia, respectively. They were compared to age
      and gender-matched children without dyslipidemia, with respect to co-morbidities
      during the 6-month prior to and 12-month after the first dyslipidemic laboratory
      value or diagnosis/treatment. RESULTS: Seven per cent of the children who had
      laboratory values available in the database had a cholesterol test during the
      study period. Only 15% of laboratory-defined children (n = 23,475) had a
      dyslipidemia diagnosis. Cholesterol-modifying medications were rarely prescribed.
      Substantially more laboratory-defined children than their comparators were obese
      (8 times), had diabetes mellitus (10 times), or had hypertension (5 times). These
      co-morbidities were even higher among diagnosis/treatment-defined children.
      CONCLUSIONS: The rate of lipid testing among children was low. The ICD-9-CM
      diagnostic codes showed low sensitivity against laboratory definitions. Though
      only a small proportion of dyslipidemic children were diagnosed or treated with a
      medication, co-morbidities associated with dyslipidemia were common.

PMID- 20035529
TI  - Randomized clinical trial comparing open with video-assisted minimally invasive
      parathyroid surgery for primary hyperparathyroidism.
AB  - BACKGROUND: : Previous studies of video-assisted techniques for parathyroidectomy
      in patients with primary hyperparathyroidism have found similar or better results
      compared with bilateral neck exploration. The aim of the present study was to
      compare open minimally invasive parathyroidectomy with the video-assisted
      technique for primary hyperparathyroidism in a multicentre randomized trial.
      METHODS: : Some 143 patients were randomized to open (n = 75) or video-assisted
      (n = 68) parathyroidectomy after positive sestamibi scintigraphy. There were no
      differences in preoperative data. The open operation was performed through a 15
      mm incision. The video-assisted techniques used were minimally invasive video
      assisted parathyroidectomy (MIVAP) or video-assisted parathyroidectomy using the
      lateral approach (VAPLA). Data were collected prospectively including
      postoperative pain scoring. RESULTS: : The procedure was significantly quicker
      for the open compared to the video assisted operations: mean(s.d.) 60(35) versus
      84(47) min (P = 0.001). Both groups of patients had similar conversion rates and
      the same outcome, with comparable incision lengths, low scores for postoperative
      neck discomfort, high cosmetic satisfaction and low complication rates.
      CONCLUSION: : Open minimally invasive parathyroidectomy for primary
      hyperparathyroidism was quicker than either video-assisted technique.
      REGISTRATION NUMBER: NCT00877981 (http://www.clinicaltrials.gov)

PMID- 20035530
TI  - Randomized clinical trial of laparoscopic gastric bypass versus laparoscopic
      duodenal switch for superobesity.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic
      biliopancreatic diversion with duodenal switch (LDS) are surgical options for
      superobesity. A randomized trial was conducted to evaluate perioperative (30-day)
      safety and 1-year results. METHODS: Sixty patients with a body mass index (BMI)
      of 50-60 kg/m(2) were randomized to LRYGB or LDS. BMI, percentage of excess BMI
      lost, complications and readmissions were compared between groups. RESULTS:
      Patient characteristics were similar in the two groups. Mean operating time was
      91 min for LRYGB and 206 min for LDS (P < 0.001). One LDS was converted to open
      surgery. Early complications occurred in four patients undergoing LRYGB and seven
      having LDS (P = 0.327), with no deaths. Median stay was 2 days after LRYGB and 4
      days after LDS (P < 0.001). Four and nine patients respectively had late
      complications (P = 0.121). Mean BMI at 1 year decreased from 54.8 to 38.5 kg/m(2)
      after LRYGB and from 55.2 to 32.5 kg/m(2) after LDS; percentage of excess BMI
      lost was greater after LDS (74.8 versus 54.4 per cent; P < 0.001). CONCLUSION:
      LRYGB and LDS can be performed with comparable perioperative safety in superobese
      patients. LDS provides greater weight loss in the first year.

PMID- 20035531
TI  - Randomized clinical trial of symptom control after stapled anopexy or diathermy
      excision for haemorrhoid prolapse.
AB  - BACKGROUND: : This multicentre randomized clinical trial studied how symptoms
      improved after either stapled anopexy or diathermy excision of haemorrhoids.
      METHODS: : The study involved 18 hospitals in Sweden, Denmark and the UK. Some
      207 patients were randomized to either anopexy or Milligan-Morgan
      haemorrhoidectomy, of whom 90 in each group were operated on. Patients reported
      symptoms before surgery and after 1 year. Daily postoperative pain scores were
      recorded in a patient diary. Surgeons evaluated the anal anatomy before surgery
      and after 1 year. RESULTS: : Correction of prolapse in the anopexy and
      haemorrhoidectomy groups was similar at 1 year (88 and 90 per cent respectively;
      P = 0.80). Freedom from symptoms was obtained in 44 and 69 per cent respectively
      (P = 0.002). Stapled anopexy was associated with less postoperative pain, which
      resolved more quickly (P = 0.004). Significant improvements were noted in anal
      continence and well-being 1 year after both operations (P < 0.001). Excessive
      pain was the most common complication after diathermy excision and disturbed
      bowel function after stapled anopexy. CONCLUSION: : Haemorrhoidal prolapse was
      corrected equally by either operation. Diathermy haemorrhoidectomy gave better
      symptom relief but was more painful. Neither operation provided complete cure but
      well-being was greatly improved. REGISTRATION NUMBER: ISRCTN68315343
      (http://www.controlled-trials.com).

PMID- 20035532
TI  - Skeletal muscle contractile properties and proinflammatory cytokine gene
      expression in human endotoxaemia.
AB  - BACKGROUND: Muscle dysfunction associated with sepsis contributes to morbidity
      and mortality but the underlying mechanisms are unclear. This study examined
      whether muscle weakness relates to an intrinsic defect in contraction, or to
      central mechanisms associated with acute illness, and whether systemic
      endotoxaemia induces changes in gene expression for proinflammatory cytokines
      within human muscle in vivo. METHODS: In this experimental study, 12 healthy men
      received intravenous Escherichia coli lipopolysaccharide (LPS, 4 ng/kg) or saline
      (control). Voluntary and electrically stimulated quadriceps contraction, and
      tumour necrosis factor (TNF) alpha mRNA expression in quadriceps muscle biopsies
      were studied before and after the infusion. RESULTS: Endotoxaemia induced
      transient weakness of voluntary quadriceps contraction, equivalent to a 7.8 (95
      per cent confidence interval 2.1 to 13.5) per cent reduction in contractile force
      at 180 min (P = 0.027) and a 9.0 (5.2 to 12.8) per cent reduction at 300 min (P =
      0.008). Electrically stimulated contraction was unaffected. LPS administration
      resulted in an apparent fibre-specific induction of TNF-alpha mRNA. CONCLUSION:
      Endotoxaemia results in a reduction in voluntary muscle contractile force without
      an apparent defect in stimulated muscle contraction. Loss of volition may be a
      more important factor than intrinsic dysfunction in acute sepsis-associated human
      muscle weakness.

PMID- 20035533
TI  - Estimating time to steady state using the effective rate of drug accumulation.
AB  - Unless all of a drug is eliminated during each dosing interval, the plasma
      concentrations within a dosing interval will increase until the time course of
      change in plasma concentrations becomes invariant from one dosing interval to the
      next, resulting in steady state. A simple method for estimating drug
      concentration time to steady state based on multiple dose area under the plasma
      concentration-time curve and effective rate of drug accumulation is presented.
      Several point estimates and confidence intervals for time to 90% of steady state
      are compared, and a recommendation is made on how to summarize and present the
      results.

PMID- 20035535
TI  - Influence of hysterectomy on fistula formation in women with diverticulitis.
AB  - BACKGROUND: : Diverticulitis is a risk factor for fistula formation but little is
      known about the influence of hysterectomy in this association. A population-based
      nationwide matched cohort study was performed to determine the risk of fistula
      formation in hysterectomized women with, and without, diverticulitis. METHODS: :
      Women who had a hysterectomy between 1973 and 2003, and a matched control cohort,
      were identified from the Swedish Inpatient Register. Incidence of diverticulitis
      and fistula surgery was determined by cross-linkage to the Register, and risk was
      estimated using a Cox regression model. RESULTS: : In a cohort of 168 563
      hysterectomized and 614 682 non-hysterectomized women (mean follow-up 11.0 and
      11.5 years respectively), there were 14 051 cases of diverticulitis and 851
      fistulas. Compared with women who had neither hysterectomy nor diverticulitis,
      the risk of fistula surgery increased fourfold in hysterectomized women without
      diverticulitis (hazard ratio (HR) 4.0 (95 per cent confidence interval (c.i.) 3.5
      to 4.7)), sevenfold in non-hysterectomized women with diverticulitis (HR 7.6 (4.8
      to 12.1)) and 25-fold in hysterectomized women with diverticulitis (HR 25.2 (15.5
      to 41.2)). CONCLUSION: : Diverticulitis, and to a lesser extent hysterectomy, is
      strongly associated with the risk of fistula formation. Hysterectomized women
      with diverticulitis have the highest risk of developing surgically managed
      fistula.

PMID- 20035536
TI  - Alkaline phosphatase predicts calcium requirements after total parathyroidectomy
      in patients receiving dialysis.
AB  - BACKGROUND: : It can be difficult to achieve a stable serum calcium level after
      parathyroidectomy for renal hyperparathyroidism. This study examined the impact
      of a calcium replacement protocol guided by predicted need in reducing hospital
      stay. METHODS: : This two-phase observational study included patients receiving
      dialysis who underwent parathyroidectomy. In the initial phase, a standard
      protocol was followed whereby oral calcium was gradually titrated upwards based
      on serum calcium levels. The protocol was revised in the second phase such that
      patients were 'loaded' with the predicted elemental calcium requirement
      immediately after surgery. RESULTS: : Forty-four patients were treated according
      to the standard protocol and 34 using the new protocol. There was a strong
      correlation between postoperative elemental calcium requirement and admission
      serum alkaline phosphatase level (ALP) (r(s) = 0.711, P < 0.001). Postoperative
      hospital stay was reduced from a median (range) of 5 (3-12) to 3 (2-7) days after
      introduction of the revised protocol as a result of better calcium balance (P <
      0.001). Multivariable analysis confirmed that use of the revised protocol was the
      main predictor of length of stay. CONCLUSION: : ALP can predict postoperative
      calcium requirements and streamline hospital stay by guiding replacement therapy.

PMID- 20035537
TI  - Quality of life after transperineal rectosigmoidectomy.
AB  - BACKGROUND: : This study evaluated continence, constipation and quality of life
      before and after perineal rectosigmoidectomy for full-thickness rectal prolapse.
      METHODS: : Consecutive patients with full-thickness rectal prolapse undergoing
      perineal rectosigmoid- ectomy (Altemeier's procedure) between May 2004 and June
      2008 were studied. A standardized questionnaire, including the Cleveland Clinic
      Constipation Score (CCCS), Cleveland Clinic Incontinence Score (CCIS) and quality
      of life scores (EuroQol-Five Dimensions, EuroQol-Visual Analogue Scale and
      Patient Assessment of Constipation-Quality of Life (PAC-QOL)), was administered
      before and after operation. RESULTS: : Thirty-eight patients (32 women) of
      mean(s.d.) age 75(13) years underwent rectosigmoid- ectomy. Seven patients
      developed postoperative complications and one died. There was one recurrence 5
      months after surgery. Twenty-nine patients completed the follow-up questionnaire
      and were reviewed after a median of 24 (range 6-48) months. Constipation and
      incontinence were significantly improved after surgery (mean CCCS from 10.21 to
      3.58 and CCIS from 14.17 to 11.42; P < 0.001). Quality of life, in terms of
      mobility, usual activities, pain/discomfort and anxiety/depression, were
      significantly better at follow-up (P < 0.001), as was subjective health status (P
      < 0.001). The PAC-QOL score improved significantly in all dimensions (P < 0.001).
      CONCLUSION: : Transperineal rectosigmoidectomy improves general and constipation
      related quality of life with good functional results.

PMID- 20035538
TI  - Factors associated with recurrence and survival following hepatectomy for large
      hepatocellular carcinoma: a multicenter analysis.
AB  - BACKGROUND: Optimal management of large (>5 cm) hepatocellular carcinoma (HCC)
      remains controversial. We sought to determine the factors associated with
      recurrence and survival for patients with large HCC following hepatectomy.
      METHODS: An analysis of a combined prospective database from two tertiary care
      centers was performed on consecutive patients who underwent hepatectomy for HCC >
      5 cm. Univariate and multivariate analyses were performed to determine factors
      associated with recurrence, disease-free (DFS) and overall survival (OS).
      RESULTS: Seventy-eight patients were identified: 32 (41%) had hepatic fibrosis.
      Forty-six patients (59%) underwent a major hepatectomy with a morbidity rate of
      41% and a mortality rate of 13%. Fibrosis was associated with male gender (P =
      0.045), hepatitis C (P = 0.003), higher Child-Pugh (P < 0.0001) and Okuda score
      (P = 0.002), smaller tumors (6.25 cm vs. 10.5 cm; P < 0.001), positive-margin
      resection (P = 0.01), and death (P = 0.047). Factors associated with recurrence
      include tumor multifocality (P = 0.03) and vascular invasion (P = 0.02).
      Predictors of OS include multifocal tumors (P = 0.05), margin status (P = 0.02),
      vascular invasion (P = 0.01), and treatment complications (P = 0.004). The median
      overall DFS and OS were 12 and 20 months, respectively. Fibrosis had no impact on
      DFS (P = 0.24) or OS (P = 0.20). CONCLUSIONS: For patients with HCC larger than 5
      cm, tumor-related factors predict outcomes and survival.

PMID- 20035539
TI  - Resection margins and other prognostic factors regarding surgically treated
      glottic carcinomas.
AB  - BACKGROUND AND OBJECTIVES: This study aims to assess the prognostic significance
      of free histopathologic margins in the surgical treatment of glottic cancer.
      Furthermore, it evaluates other prognostic factors regarding cases that receive
      surgical management for glottic lesions. METHODS: A retrospective case-series
      study was conducted at an academic tertiary referral center. The files of 1,314
      cases that underwent primary surgical treatment for glottic cancer were studied.
      Various prognostic factors, including age, surgical procedure, T classification,
      N classification, histological grade, and status of margins were assessed in
      univariate and multivariate analyses. All variables were investigated for their
      association with local and regional disease control as well as disease specific
      and overall survival. RESULTS: Status of margins significantly affected disease
      specific survival and local control regardless of tumor stage in this series. All
      other variables assessed in the univariate analysis for their association with
      survival were also found to be significant. However, status of surgical margins
      and N classification were the only significant variables in multivariate
      analysis. CONCLUSION: The prognostic value of negative surgical margins for the
      treatment of glottic cancer cannot be overestimated. Responsibility of the
      surgeon during primary surgical treatment of glottic carcinomas is emphasized.

PMID- 20035540
TI  - Consolidation hyperthermic intraperitoneal chemotherapy using paclitaxel in
      patients with epithelial ovarian cancer.
AB  - BACKGROUND: We evaluated the efficacy and feasibility of hyperthermic
      intraperitoneal chemotherapy (HIPEC) using paclitaxel as consolidation therapy in
      patients with epithelial ovarian cancer. METHODS: Between November 1999 and
      January 2004, 18 patients with a negative second-look and 1 patient with positive
      peritoneal cytology only with stage Ic-IIIc epithelial ovarian cancer received
      consolidation intra-operative HIPEC using paclitaxel. The HIPEC was performed
      with open-abdomen technique, using 6 L of lactated Ringer's solution containing
      paclitaxel 175 mg/m(2), for 90 min in hyperthermic phase (43-44 degrees C). The
      survival rates were compared with 24 patients treated with conventional therapy
      (control group). RESULTS: The 8-year progression-free survival rates were 63.16%
      in the HIPEC-paclitaxel group and 29.17% in the control group (P = 0.027). The 8
      year overall survival rates were 84.21% in the HIPEC-paclitaxel group and 25.00%
      in the control group (P = 0.0004). The time interval between initial treatment
      and HIPEC was statistically significant with respect to progression-free and
      overall survival in the HIPEC-paclitaxel group. CONCLUSION: HIPEC with paclitaxel
      during 2nd-look laparotomy is feasible and relatively safe and showed a good
      effect on survival. In patients with epithelial ovarian cancer who have a
      complete pathologic response, HIPEC with paclitaxel should be considered as a
      consolidation treatment option.

PMID- 20035541
TI  - Randomized clinical trial of radiofrequency ablation or conventional high
      ligation and stripping for great saphenous varicose veins.
AB  - BACKGROUND: This randomized clinical trial compared early outcomes after
      radiofrequency ablation (RFA) and conventional surgery for varicose veins.
      METHODS: Consecutive patients with symptomatic varicose veins due to isolated
      great saphenous vein (GSV) incompetence and suitable for RFA were randomized to
      either RFA or conventional surgery (saphenofemoral disconnection and stripping).
      Clinical, radiological and patient-based outcomes were recorded at 1 and 5 weeks
      after intervention. RESULTS: RFA resulted in successful obliteration of the GSV
      in all 47 patients. Complete above-knee stripping was unsuccessful in seven of 41
      patients. RFA took longer than conventional surgery: median interquartile range
      76 (67-84) versus 48 (39-54) min; P < 0.001. Patients returned to their normal
      activities significantly earlier after RFA (median 3 (2-5) versus 12.5 (4-21)
      days; P < 0.001). Postoperative pain was significantly less after RFA (median
      score on visual analogue scale 1.70 (0.50-4.30) versus 4.0 (2.35-6.05); P =
      0.001). Patient satisfaction, quality of life improvement and analgesic
      requirements significantly favoured RFA. CONCLUSION: RFA took longer to perform
      but resulted in a significantly better early outcome than conventional surgery in
      suitable patients with great saphenous varicose veins.

PMID- 20035542
TI  - Comparison of magnetic resonance imaging-fluorodeoxy- glucose positron emission
      tomography fusion with pathological staging in rectal cancer.
AB  - BACKGROUND: : This study represents an initial experience with combined magnetic
      resonance imaging (MRI) and [(18)F]fluorodeoxyglucose positron emission
      tomography (FDG PET) (MRI-PET fusion) in the primary staging of rectal carcinoma.
      METHODS: : A retrospective analysis of data recorded on patients with rectal
      cancer was undertaken. Patients requiring long-course radiotherapy were excluded.
      Chest radiography, abdominal computed tomography and endorectal ultrasonography
      were performed. In addition, MRI of the pelvis, whole-body FDG PET and MRI-PET
      fusion were carried out. All patients subsequently underwent anterior resection.
      RESULTS: : Twenty-three patients with rectal carcinoma (15 men), of median age 60
      (range 46-75) years, were enrolled. In tumour (T) assessment, MRI correctly
      staged 14 of 22 T2/T3 tumours. In lymph node assessment, MRI-PET fusion had a
      sensitivity of 44 per cent, with a specificity and positive predictive value of
      100 per cent. No additional information was acquired from MRI-PET fusion over MRI
      plus abdominal computed tomography and chest radiography. CONCLUSION: : MRI-PET
      fusion adds little to conventional investigations for staging rectal carcinoma.

PMID- 20035543
TI  - Mid-term outcome of endovascular revascularization for chronic mesenteric
      ischaemia.
AB  - BACKGROUND: : This study aimed to assess mid-term outcome after endovascular
      revascularization of chronic occlusive mesenteric ischaemia (CMI) and to identify
      possible predictors of mortality. METHODS: : Consecutive patients undergoing
      primary elective stenting for CMI between 1995 and 2007 were registered
      prospectively in a database. Patients with acute ischaemia were excluded.
      Retrospective case-note review and data analysis were performed. RESULTS: : Forty
      three patients (10 men) were treated for stable (n = 30) or exacerbated (n = 13)
      CMI. Their median (interquartile range (i.q.r.)) age was 70 (60-79) years.
      Revascularization was successful in 47 of 49 vessels. The superior mesenteric
      artery (SMA), either alone (n = 34) or in combination with the coeliac trunk (n =
      6), was the predominant target vessel. No patient died within 30 days. Median
      follow-up was 43 (i.q.r. 25-63) months and the estimated (s.e.) 3-year overall
      survival rate was 76(7) per cent. Two patients died from distal SMA occlusive
      disease and intestinal infarction after 6 and 18 months respectively. Previous
      stroke (P = 0.016), male sex (P = 0.057) and age (P = 0.066) were associated with
      mid-term mortality on univariable, but not multivariable analysis. Reintervention
      was needed in 14 patients, achieving a 3-year cumulative rate of freedom from
      recurrent symptoms of 88(5) per cent. CONCLUSION: : Endovascular treatment
      provided high early and mid-term survival rates in this series of patients with
      CMI, with low complication rates.

PMID- 20035544
TI  - Commentary on Cost- utility and value-of-information analysis of early versus
      delayed laparoscopic cholecystectomy for acute cholecystitis (Br J Surg 2010; 97:
      210- 219).

PMID- 20035545
TI  - Cost-utility and value-of-information analysis of early versus delayed
      laparoscopic cholecystectomy for acute cholecystitis.
AB  - BACKGROUND: : A recent systematic review found early laparoscopic cholecystectomy
      (ELC) to be safe and to shorten total hospital stay compared with delayed
      laparoscopic cholecystectomy (DLC) for acute cholecystitis. The cost
      effectiveness of ELC versus DLC for acute cholecystitis is unknown. METHODS: : A
      decision tree model estimating and comparing costs to the UK National Health
      Service (NHS) and quality-adjusted life years (QALYs) gained following a policy
      of either ELC or DLC was developed with a time horizon of 1 year. Uncertainty was
      investigated with probabilistic sensitivity analysis, and value-of-information
      analysis estimated the likely return from further investment in research in this
      area. RESULTS: : ELC is less costly (approximately - pound820 per patient) and
      results in better quality of life (+0.05 QALYs per patient) than DLC. Given a
      willingness-to-pay threshold of pound20 000 per QALY gained, there is a 70.9 per
      cent probability that ELC is cost effective compared with DLC. Full
      implementation of ELC could save the NHS pound8.5 million per annum. CONCLUSION:
      : The results of this decision analytic modelling study suggest that on average
      ELC is less expensive and results in better quality of life than DLC. Future
      research should focus on quality-of-life measures alone.

PMID- 20035546
TI  - Meta-analysis of randomized controlled trials on the safety and effectiveness of
      early versus delayed laparoscopic cholecystectomy for acute cholecystitis.
AB  - BACKGROUND: : In many countries laparoscopic cholecystectomy for acute
      cholecystitis is mainly performed after the acute episode has settled because of
      the anticipated increased risk of morbidity and higher conversion rate from
      laparoscopic to open cholecystectomy. METHODS: : A systematic review was
      performed with meta-analysis of randomized clinical trials of early laparoscopic
      cholecystectomy (ELC; performed within 1 week of onset of symptoms) versus
      delayed laparoscopic cholecystectomy (performed at least 6 weeks after symptoms
      settled) for acute cholecystitis. Trials were identified from The Cochrane
      Library trials register, Medline, Embase, Science Citation Index Expanded and
      reference lists. Risk ratio (RR) or mean difference was calculated with 95 per
      cent confidence intervals (c.i.) based on intention-to-treat analysis. RESULTS: :
      Five trials with 451 patients were included. There was no significant difference
      between the two groups in terms of bile duct injury (RR 0.64 (95 per cent c.i.
      0.15 to 2.65)) or conversion to open cholecystectomy (RR 0.88 (95 per cent c.i.
      0.62 to 1.25)). The total hospital stay was shorter by 4 days for ELC (mean
      difference -4.12 (95 per cent c.i. -5.22 to -3.03) days). CONCLUSION: : ELC
      during acute cholecystitis appears safe and shortens the total hospital stay.

PMID- 20035547
TI  - Independent changes in female body shape with parity and age: A life-history
      approach to female adiposity.
AB  - Both aging and reproduction have been shown to influence female body shape in
      industrialized populations, involving redistribution of fat from lower to upper
      body regions. However, the extent to which effects of parity vary by age and the
      extent to which age affects shape independent of parity remain unclear. We
      studied shape variability in relation to age and parity in a cross-sectional
      survey of 4,130 white British women, using three-dimensional photonic scanning.
      In women < or =40 years, bearing children was associated with increased abdominal
      and reduced thigh girths, independent of age and BMI. Very few such differences
      were statistically significant in women >40 years, suggesting the effects of
      parity on shape wash out over time. In nulliparous women, aging was associated
      with shape variability, independent of BMI, with a similar pattern of
      associations evident in women both < or =40 and >40 years. Our data support
      previous findings of "covert maternal depletion" in relation to parity, but show
      that this is merely a more pronounced component of a general strategic shift of
      fat from lower to upper body with age. These findings are consistent with a life
      history model of female energy stores being allocated to competing "reproduction"
      and "maintenance" depots, with the optimal trade-off strategy changing with age
      and with that strategic shift accelerated by bearing children. This model is
      relevant to the "grandmother hypothesis." The dual effects of age and parity on
      fat distribution substantially resolve by old age the profound sexual dimorphism
      in adiposity present at the start of adult life.

PMID- 20035548
TI  - Peer and cyber aggression in secondary school students: the role of moral
      disengagement, hostile attribution bias, and outcome expectancies.
AB  - This study investigated the relationship between cognitive mechanisms, applied by
      people to rationalize and justify harmful acts, and engagement in traditional
      peer and cyber aggression among school children. We examined the contribution of
      moral disengagement (MD), hostile attribution bias, and outcome expectancies, and
      we further explored the individual contribution of each MD mechanism. Our aim was
      to identify shared and unique cognitive factors of the two forms of aggression.
      Three hundred and thirty-nine secondary school children completed self-report
      measures that assessed MD, hostile attribution bias, outcome expectancies, and
      their roles and involvement in traditional and cyber aggression. We found that
      the MD total score positively related to both forms of peer-directed aggression.
      Furthermore, traditional peer aggression positively related to children's moral
      justification, euphemistic language, displacement of responsibility and outcome
      expectancies, and negatively associated with hostile attribution bias. Moral
      justification also related positively to cyber aggression. Cyber aggression and
      cyber victimization were associated with high levels of traditional peer
      aggression and victimization, respectively. The results suggest that MD is a
      common feature of both traditional and cyber peer aggression, but it seems that
      traditional forms of aggression demand a higher level of rationalization or
      justification. Moreover, the data suggest that the expectation of positive
      outcomes from harmful behavior facilitates engagement in traditional peer
      aggression. The differential contribution of specific cognitive mechanisms
      indicates the need for future research to elaborate on the current findings, in
      order to advance theory and inform existing and future school interventions
      tackling aggression and bullying.

PMID- 20035549
TI  - Deleterious effects of plant cystatins against the banana weevil Cosmopolites
      sordidus.
AB  - The general potential of plant cystatins for the development of insect-resistant
      transgenic plants still remains to be established given the natural ability of
      several insects to compensate for the loss of digestive cysteine protease
      activities. Here we assessed the potential of cystatins for the development of
      banana lines resistant to the banana weevil Cosmopolites sordidus, a major pest
      of banana and plantain in Africa. Protease inhibitory assays were conducted with
      protein and methylcoumarin (MCA) peptide substrates to measure the inhibitory
      efficiency of different cystatins in vitro, followed by a diet assay with
      cystatin-infiltrated banana stem disks to monitor the impact of two plant
      cystatins, oryzacystatin I (OC-I, or OsCYS1) and papaya cystatin (CpCYS1), on the
      overall growth rate of weevil larvae. As observed earlier for other Coleoptera,
      banana weevils produce a variety of proteases for dietary protein digestion,
      including in particular Z-Phe-Arg-MCA-hydrolyzing (cathepsin L-like) and Z-Arg
      Arg-MCA-hydrolyzing (cathepsin B-like) proteases active in mildly acidic
      conditions. Both enzyme populations were sensitive to the cysteine protease
      inhibitor E-64 and to different plant cystatins including OsCYS1. In line with
      the broad inhibitory effects of cystatins, OsCYS1 and CpCYS1 caused an important
      growth delay in young larvae developing for 10 days in cystatin-infiltrated
      banana stem disks. These promising results, which illustrate the susceptibility
      of C. sordidus to plant cystatins, are discussed in the light of recent
      hypotheses suggesting a key role for cathepsin B-like enzymes as a determinant
      for resistance or susceptibility to plant cystatins in Coleoptera.

PMID- 20035550
TI  - Evaluation of ovotoxicity in female mice caused by organic extracts in tap water
      from Jialing River in Chongqing, China.
AB  - BACKGROUND: Recently, toxic effects of widespread organic pollutants have
      received much attention due to the hazards they pose to female reproductive
      health. The aim of the present study was to determine the female reproductive
      toxicity of organic extracts (OE) in tap water from the Jialing River in
      Chongqing, China. METHODS: In our experiment, Kunming female mice that exhibited
      normal estrous cycles were randomly divided into 4 groups, which included a
      control group (OE 0 L/kg bw) as well as low- (OE 12.5 L/kg bw/day), mid- (OE 25
      L/kg bw/day), and high-dose (OE 50 L/kg bw/day) groups. Mice were continually
      administered intraperitoneal injections of OE at different doses for 5
      consecutive days. On the 15th and 30th day after treatments, half of the mice
      were sacrificed separately. RESULTS: The results showed that OE decreased
      relative ovary weights and prolonged the duration of estrous cycle with
      concomitant increase in estrous phase. There was a significant decrease in the
      number of corpora lutea of OE-treated mice, but no significant differences were
      found in healthy and atretic follicle populations compared to control.
      Ultrastructure observation regarding granulosa cells of the ovary revealed that
      OE treatment caused mitochondrial swelling together with endoplasmic reticulum
      expansion. CONCLUSIONS: All these data indicate that OE could exert adverse
      effects on the development of ovary and also a slight suppressive effect on
      reproductive functions.

PMID- 20035551
TI  - Dip-pen nanolithography on SiOx and tissue-derived substrates: comparison with
      multiple biological inks.
AB  - There has been extensive interest in the micro and nanoscale manipulation of
      various substrates in the past few decades. One promising technique is dip-pen
      nanolithography which has shown the capability to pattern substrates of all forms
      including, tissue-derived substrates. Patterning of tissue-derived substrates is
      of particular interest, as it would facilitate studies into controlling cell
      morphology and cell-substrate interaction. To expand the field into this area
      both peptides and bioactive collagen-binding peptide-linked biomolecules were
      patterned to the inner collagenous zone of the Bruch's membrane (BM). Collagen
      binding peptide, and extra cellular matrix (ECM) proteins laminin and fibronectin
      were patterned on the BM and SiO(x). The lithographic protocol was facilitated by
      Triton X-100 which was used to clean the tissue-derived construct after
      harvesting. This produced a collagen-exposed BM which was more hydrophilic
      (contact angle 67 degrees +/-8.49 degrees) surface compared with other cleaning
      methods but it maintained similar surface roughness (root-mean-square) 80+/-18 nm
      and collagen exposure. This type of surface can be readily patterned with the
      chosen inks under lower humidity conditions.

PMID- 20035552
TI  - Gonadal apoptosis during sex reversal of the rice field eel: implications for an
      evolutionarily conserved role of the molecular chaperone heat shock protein 10.
AB  - Role of apoptosis in gonadal transformation of the rice field eel remains
      unknown. Here we report characterization of apoptotic pattern of testis, ovary,
      and ovotestis of the rice field eel, a vertebrate with natural sex reversal
      characteristic. DNA laddering assay showed typical ladder with step around 200 bp
      in the gonads, especially in testis. Terminal transferase dUTP nick end labeling
      on gonads indicated obvious apoptotic signals in the seminiferous tubules.
      Western blot analysis revealed that pro-apoptotic genes, Caspase 9 and p53, were
      upregulated and anti-apoptotic factor Bcl2 was downregulated in testis compared
      with both ovary and ovotestis. These data indicated that sex reversal process is
      accompanied by gonadal apoptosis with the highest proportion of cell death in the
      testis. Furthermore, we identified the Hsp10 by differentially screening of
      testis, ovary, and ovotestis using microarray technique, which is evolutionarily
      conserved and differentially expressed during gonadal transformation.
      Downregulation of Hsp10 is consistent with high apoptosis during the gonadal
      transformation. Flow cytometry assay confirmed that Hsp10 inhibits the apoptosis
      in male gonadal cells. Moreover, upregulation and mis-localization at sub
      cellular level of the HSP10 together with its partner HSP60 is associated with
      tumorigenesis in human testis. These results suggest that downregulation of Hsp10
      would be one of the main causes of apoptosis in testis, overexpression of Hsp10
      suppresses apoptosis, and potentially results in testis tumorigenesis, which
      provide clues for understanding the mechanisms of germ cell apoptosis.
      Development of Hsp10 as a diagnostic marker or even treatment target will be
      promising in testis cancer diagnosis and therapy.

PMID- 20035553
TI  - Physician, heal thyself.

PMID- 20035554
TI  - [History of neurology in Japan. Interview by Shinichi Takasaka].

PMID- 20035556
TI  - Leuconicines A-G and (-)-eburnamaline, biologically active strychnan and eburnan
      alkaloids from Leuconotis.
AB  - Seven new indole alkaloids of the Strychnos type, leuconicines A-G (1-7), and a
      new eburnan alkaloid, (-)-eburnamaline (8), were isolated from the stem-bark
      extract of two Malayan Leuconotis species. The structures of these alkaloids were
      established using NMR and MS analysis and in the case of 8 also by partial
      synthesis. Alkaloids 1-5 reversed multidrug resistance in vincristine-resistant
      KB cells.

PMID- 20035555
TI  - Inhibition of protein phosphorylation in MIA pancreatic cancer cells: confluence
      of metabolic and signaling pathways.
AB  - Oxythiamine (OT), a transketolase inhibitor, is known to inhibit pancreatic
      cancer cell proliferation. In this study, we investigated the effect of
      inhibition of the transketolase pathway on signaling pathways in MIA PaCa cancer
      cells using in-house proteomic techniques. We hypothesized that OT alter protein
      phosphorylation thus affecting cell cycle arrest and cell proliferation. MIA PaCa
      2 cells were cultured in media containing an algal (15)N amino acid mixture at
      50% enrichment, with and without OT, to determine protein expression and
      synthesis. Analysis of cell lysates using two-dimensional gel electrophoresis
      matrix assisted laser desorption and ionization time-of-flight and time-of-flight
      mass spectrometry (2-DE-MALDI-TOF/TOF MS) identified 12 phosphor proteins that
      were significantly suppressed by OT treatment. Many of these proteins are
      involved in regulation of cycle activities and apoptosis. Among the proteins
      identified, expression of the phosphor heat shock protein 27 (Hsp27) was
      dramatically inhibited by OT treatment while the level of its total protein
      remained unchanged. Hsp27 expression and phosphorylation is known to be
      associated with drug resistance and cancer cell survival. The changes in
      phosphorylation of key proteins of cancer proliferation and survival suggest that
      protein phosphorylation is the confluence of the effects of OT on metabolic and
      signaling pathways.

PMID- 20035557
TI  - Antimycobacterial flavonoids from the leaf extract of Galenia africana.
AB  - The bioassay-guided fractionation of the EtOH extract of the leaves of Galenia
      africana led to the isolation of three known flavonoids, (2S)-5,7,2'
      trihydroxyflavanone (1), (E)-3,2',4'-trihydroxychalcone (2), and (E)-2',4'
      dihydroxychalcone (3), and the new (E)-3,2',4'-trihydroxy-3'-methoxychalcone (4).
      Compounds 1 and 3 exhibited moderate antituberculosis activity. During
      synergistic studies, a combination of compound 4 and an existing antituberculosis
      drug, isoniazid, reduced their original MICs 4-fold, resulting in a fractional
      inhibitory concentration of 0.50. The most pronounced effect was demonstrated by
      compound 1 and isoniazid reducing their MICs 16-fold and resulting in an FIC of
      0.12. Both EtOH extract and isolated compounds failed to exhibit any NADPH
      oxidase activity at 800.0 muM concentrations, indicating that mycothiol disulfide
      reductase is not the target for their antituberculosis activity.

PMID- 20035558
TI  - ThermoData engine (TDE): software implementation of the dynamic data evaluation
      concept. 4. Chemical reactions.
AB  - ThermoData Engine (TDE) is the first full-scale software implementation of the
      dynamic data evaluation concept, as reported recently in this journal. This paper
      describes the first application of this concept to the evaluation of
      thermodynamic properties for chemical reactions. Reaction properties evaluated
      are the enthalpies, entropies, Gibbs energies, and thermodynamic equilibrium
      constants. Details of key considerations in the critical evaluation of enthalpies
      of formation and of standard entropies for organic compounds are discussed in
      relation to their application in the calculation of reaction properties.
      Extensions to the class structure of the program are described that allow close
      linkage between the derived reaction properties and the underlying pure-component
      properties. Derivation of pure-component enthalpies of formation and of standard
      entropies through the use of directly measured reaction properties (enthalpies of
      reaction and equilibrium constants) is described. Directions for future
      enhancements are outlined.

PMID- 20035560
TI  - Ring expansion of oxyglycals. Synthesis and conformational analysis of
      septanoside-containing trisaccharides.
AB  - Oxyglycals, derived from lactose and maltose, were expanded to trisaccharides
      through a ring expansion method. Trisaccharides with 6-7-5 and 6-7-6 ring sizes
      were prepared through the ring expansion method, with high
      diastereoselectivities, in each step of their synthesis. The NOE and ROESY NMR
      spectroscopies were used to assess the dipolar couplings within the
      trisaccharide. A computational study was undertaken, from which low energy
      conformations, as well as, dihedral angles that define the glycosidic linkages
      were identified.

PMID- 20035561
TI  - Organic dyes incorporating the dithieno[3,2-b:2',3'-d]thiophene moiety for
      efficient dye-sensitized solar cells.
AB  - New dipolar compounds incorporating a dithieno[3,2-b:2',3'-d]thiophene unit as
      the electron donor, an oligothiophene moiety as the conjugated spacer, and 2
      cyanoacrylic acid as the electron acceptor have been synthesized. These
      nonarylamine type metal-free organic compounds have been successfully used as the
      sensitizers of dye-sensitized solar cells (DSSCs). The conversion efficiencies of
      the DSSCs range from 3.54 to 5.15% under AM 1.5 G irradiation. The best
      efficiency reached approximately 70% of the ruthenium dye N719-based standard
      cell fabricated and measured under similar conditions.

PMID- 20035562
TI  - Stereocontrolled synthesis of C1-C17 fragment of narasin via a free radical-based
      approach.
AB  - An efficient synthesis of the C1-C17 western unit of narasin was achieved from
      (S)-Roche ester. Highlights in our synthesis include the successful exploitation
      of three stereoselective sequences of Lewis acid mediated reaction followed by
      free-radical-based hydrogen transfer.

PMID- 20035563
TI  - A phosphine-mediated construction of 1,4-oxazepines and 1,3-oxazines.
AB  - A simple and efficient method for constructing 1,4-oxazepines and 1,3-oxazines
      was developed with use of a phosphine-mediated tandem reaction of ynones with 2
      azido alcohols. The method offers a promising route to synthetically useful as
      well as biologically active heterocycles under mild conditions and may be
      exploited for the preparation of interesting chiral ligands.

PMID- 20035564
TI  - Multiple-turnover isotopic labeling of Fmoc- and Boc-protected amino acids with
      oxygen isotopes.
AB  - An efficient method for the selective isotopic labeling of carboxylic acids is
      reported. By reacting an amino acid with excess carbodiimide and (18)OH(2), a
      kinetically enhanced multiple turnover reaction provides the (18)O-labeled
      product in high yield and excellent isotopic enrichment. This reaction is fully
      compatible with standard Fmoc, Boc, Trt, and OtBu protecting groups and provides
      a means to selectively label the alpha-carboxylic acids of functionalized amino
      acids with stable oxygen isotopes.

PMID- 20035565
TI  - Iron-mediated radical nitro-cyclization reaction of 1,6-dienes.
AB  - Sequential steps that involved radical addition of a nitro group to 1,6-dienes
      promoted by the thermal decomposition of iron nitrate(III) nonahydrate,
      cyclization, and trapping of the resulting terminal radicals by a chlorine atom
      in the presence of chloride salt afforded five-membered-ring compounds. The
      present reaction provides a practical method for the synthesis of nitro compounds
      due to its simple experimental procedure and its use of nontoxic and inexpensive
      iron reagents.

PMID- 20035566
TI  - Dipyrazinyl sulfoxide complexes of silver(I), zinc(II), and cadmium(II): ligation
      modes and anion tuning.
AB  - The new ligand dipyrazinyl sulfoxide (also named sulfinyldipyrazine and
      abbreviated as pyz(2)SO) and a series of its metal complexes including
      {[Ag(pyz(2)SO)](NO(3)).CH(3)CN}(infinity) (1), {[Ag(pyz(2)SO)](PF(6))}(infinity)
      (2), [Ag(3)(pyz(2)SO)(2)(ClO(4))(3)](infinity) (3),
      [Ag(pyz(2)SO)(CF(3)CO(2))](infinity) (4),
      {[Zn(pyz(2)SO)(H(2)O)(4)](NO(3))(2).H(2)O}(infinity) (5),
      {[Zn(pyz(2)SO)(H(2)O)(2)](ClO(4))(2)}(infinity) (6), and
      {[Cd(pyz(2)SO)(2)(H(2)O)](ClO(4))(2).H(2)O}(infinity) (7) have been synthesized
      and characterized by single-crystal X-ray analysis. The counteranions in these
      complexes prefer to be embraced by a pair of pi-acidic heterocyclic rings via
      anion-pi interactions, which consequently affect the process of supramolecular
      assembly. Seven distinct ligation modes of pyz(2)SO involving various bonding
      combinations of the sulfoxide oxygen and/or pyrazinyl nitrogen atoms (labeled A
      G) are observed. Diverse coordination motifs such as (4,4) network, ladder-type,
      necklace-like, linear, and zigzag-chain structures are found in 1-7.
      Interestingly, the sulfoxide group of the pyz(2)SO ligand exhibits unusual
      dipolar sulfinyl...sulfinyl and S=O...pi(pyrazinyl) intermolecular interactions
      in the supramolecular assemblies of neat pyz(2)SO, 1, and 3-5.

PMID- 20035567
TI  - Presence or absence of a central Se atom in silver selenide/selenolate clusters
      with halite topology: syntheses and properties of [(Ph(3)PAg)(8)Ag(6)(mu(6)-Se)(1
      x/2)(SePh)(12)](x+) (x = 0, 1).
AB  - Two types of Ph(3)P/Ph ligated Ag(14)Se(13-x) (x = 0, 0.5) clusters with halite
      topology were synthesized that differ by the occupation/nonoccupation of the
      central position by a 13th Se atom and the resulting charge: neutral
      [(Ph(3)PAg)(8)Ag(6)(mu(6)-Se)(SePh)(12)].11THF (1) and ionic
      [(Ph(3)PAg)(8)Ag(6)(mu(6)-Se)(0.5)(SePh)(12)][R(3)SnCl(2)].nTHF (R = Ph, n = 6
      (2a); Cy, n = 5 (2b)) are all based on a tetradecanuclear cluster. The structural
      response on the charge was rationalized by DFT calculations, and the optical
      absorption behavior was studied.

PMID- 20035568
TI  - Fast ligand substitution at a chromium(III) hydroperoxo complex.
AB  - The hydroperoxo group in (H(2)O)(5)CrOOH(2+) is replaced with selected anions
      (acetate, nitrate, and sulfate) at rates that are unprecedented for substitution
      at a pentaaquachromium(III) complex. The chemistry is noteworthy in that it
      interchanges low-concentration, weak ligands between a Cr(III) coordination
      sphere and solution in the presence of a large excess of water. We attribute this
      chemistry and the fast kinetics to the hydroperoxo cis effect. Each of the
      entering anions follows a different rate law in support of H(+)-assisted
      dissociation of the hydroperoxo group from a mixed-ligand intermediate. The
      dependence on [H(+)] is first-order for nitrate, zero-order for acetic acid, and
      changes from first- to zero-order for sulfate in the acidity range 0.015 M <
      [H(+)] < 0.20 M. At 1.0 M H(+), the second-order rate constants are 3.0
      (nitrate), 2.49 (sulfate), and 0.90 (acetic acid) M(-1) s(-1). The similarity in
      rate constants supports a mechanism featuring rate-limiting substitution at
      chromium. The equilibrium constant for the reaction (H(2)O)(5)CrOOH(2+) + NO(3)(
      ) + H(+) <==> (H(2)O)(5)CrONO(2)(2+) + H(2)O(2), K = 62 M(-1), was obtained from
      the kinetics of forward and reverse reactions.

PMID- 20035569
TI  - Computationally designed metal-free hydrogen activation site: reaching the
      reactivity of metal-ligand bifunctional hydrogenation catalysts.
AB  - In this study, a strategy to design a metal-free hydrogen activation site has
      been proposed. On the basis of our so-called sp(3) carbon bridged FLPs
      (Frustrated Lewis Pairs), we first hypothesized that a more reactive activation
      site should arrange the nitrogen lone pair and the boron vacant orbital to lie in
      the same plane face-to-face, because such orbital orientations can simultaneously
      enhance the interaction between the nitrogen lone pair and the H(2) sigma*
      antibonding orbital and the interaction between the boron vacant orbital and the
      H(2) sigma bonding electrons. To verify that such an active site is achievable,
      we then computationally designed molecules and studied their reactions with
      hydrogen. The energetic results show the designed molecules are indeed more
      reactive than the sp(3) carbon bridged FLPs. Some of the hydrogen activations
      reach kinetics and thermodynamics comparable with those of the hydrogen
      activations mediated by the well-known metal-ligand bifunctional hydrogenation
      catalysts. The designed molecules could be the targets for experimental
      synthesis. The pattern of the proposed active site can be based to design similar
      molecules for metal-free hydrogenations.

PMID- 20035570
TI  - Arsenic-induced carcinogenesis--oxidative stress as a possible mode of action and
      future research needs for more biologically based risk assessment.
AB  - Exposure to inorganic arsenic (iAs) induces cancer in human lungs, urinary
      bladder, skin, kidney, and liver, with the majority of deaths from lung and
      bladder cancer. To date, cancer risk assessments for iAs have not relied on
      mechanistic data, as we have lacked sufficient understanding of arsenic's
      pharmacokinetics and mode(s) of carcinogenic action (MOA). Furthermore, while
      there are vast amounts of toxicological data on iAs, relatively little of it has
      been collected using experimental designs that efficiently support development of
      biologically based dose-response (BBDR) models and subsequently risk assessment.
      This review outlines an efficient approach to the development of a BBDR model for
      iAs that would reduce uncertainties in its cancer risk assessment. This BBDR
      based approach is illustrated by using oxidative stress as the carcinogenic MOA
      for iAs but would be generically applicable to other MOAs. Six major research
      needs that will facilitate BBDR model development for arsenic-induced cancer are
      (1) MOA research, which is needed to reduce the uncertainty in risk assessment;
      (2) development and integration of the pharmacodynamic component (MOA) of the
      BBDR model; (3) dose-response and extrapolation model selection; (4) the
      determination of internal human speciated arsenical concentrations to improve
      physiologically based pharmacokinetic (PBPK) models; (5) animal models of arsenic
      carcinogenesis; and (6) the determination of the low dose human relationship for
      death from cancer, particularly in lungs and urinary bladder. The major parts of
      the BBDR model are arsenic exposure, a physiologically based pharmacokinetic
      model, reactive species, antioxidant defenses, oxidative stress, cytotoxicity,
      growth factors, transcription factors, DNA damage, chromosome damage, cell
      proliferation, mutation accumulation, and cancer. The BBDR model will need to be
      developed concurrently with data collection so that model uncertainties can be
      identified and addressed through an iterative process of targeted additional
      research.

PMID- 20035571
TI  - Poly(ethylene glycol) and hydroxy functionalized alkane phosphate mixed self
      assembled monolayers to control nonspecific adsorption of proteins on titanium
      oxide surfaces.
AB  - The spontaneous formation of alkane phosphate self-assembled monolayers (SAMs) on
      titanium oxide was chosen as a tool to tailor the surface physicochemical
      properties in terms of nonspecific adsorption of proteins. For this aim,
      poly(ethylene glycol)-modified (PEG) alkane phosphate was codeposited with OH
      terminated alkane phosphates. X-ray photoelectron spectroscopy and ellipsometry
      of the resulting mixed SAMs indicate that the PEG density can be controlled by
      varying the mole fraction of PEG-terminated phosphates in the solutions used
      during the deposition process, leading to surfaces with different degrees of
      protein resistance.

PMID- 20035572
TI  - Photochromic nanostructures based on diarylethenes with perylene diimide.
AB  - A bisthienylethene-functionalized perylene diimide (BTE-PDI) photochromic dyad
      was synthesized for self-assembly into 1-D nanotubes by a reprecipitation method.
      SEM and TEM observations showed that the nanotubes were formed from their 0-D
      precursors of hollow nanospheres. HR-TEM images revealed that both the
      nanospheres and the nanotubes have highly ordered lamellar structure, indicating
      the hierarchical process during assembly. The IR and XRD results revealed that
      DAE-PDI molecules were connected through intermolecular hydrogen bonds to form
      building blocks that self-assembled into nanostructures. Electronic absorption
      and fluorescence spectroscopic results indicated the H-aggregate nature of the
      self-assembled nanostructures. Competition and cooperation between the dipole
      dipole interaction, intermolecular pi-pi stacking, and hydrophilic/hydrophobic
      interaction are suggested to result in nanostructures. Reconstruction was found
      to happen during the morphology transition progress from the 0-D nanospheres to
      the 1-D nanotubes, which was driven by donor-acceptor dipole-dipole interactions.
      Green emission at 520 nm originating from the DAE subunit was observed for the
      aggregates of vesicles and nanotubes, which could be regulated by
      photoirradiation with 365 nm light, suggesting the nanoaggregates to be
      photochromic switches.

PMID- 20035573
TI  - Neurosurgical "pearls" and neurosurgical evidence.

PMID- 20035574
TI  - Factors influencing the risk of local recurrence after resection of a single
      brain metastasis.
AB  - OBJECT: Local recurrence (LR) of a resected brain metastasis occurs in up to 46%
      of patients. Postoperative whole-brain radiation therapy (WBRT) reduces that
      incidence. To isolate factors associated with the risk of LR after resection, the
      authors only studied patients who did not receive adjuvant radiotherapy. METHODS:
      The authors reviewed data from 570 cases involving patients who had undergone
      resection of a previously untreated single brain metastasis at The University of
      Texas M. D. Anderson Cancer Center between 1993 and 2006 without receiving
      postoperative WBRT. All tumors were measured preoperatively on MR images. The
      resection method (en bloc resection [EBR] or piecemeal resection [PMR]) was noted
      at the time of surgery. Predictors of LR were assessed using the Cox proportional
      hazards model. RESULTS: The median patient age was 58 years, 55% were male, and
      88% had a Karnofsky Performance Scale Score > or = 80. The most common primary
      cancers were those of the lung (28%), skin (melanoma, 21%), kidney (19%), and
      breast (11%). Piecemeal resection was performed in 201 patients (35%) and EBR in
      369 (65%). Local recurrence developed in 84 patients (15%). The histological type
      of the primary cancer did not significantly predict LR; however, 7 of 22 patients
      with sarcoma developed LR (p = 0.16). The authors identified 2 variables that
      increased the risk of LR. Undergoing PMR carried a significantly higher LR risk
      than EBR (crude hazard ratio [HR] 1.7, 95% CI 1.1-2.6, p = 0.03). Tumors
      exceeding the median volume (9.7 cm(3)) had a significantly higher LR risk than
      those that were < 9.7 cm(3) (crude HR 1.7; 95% CI 1.1-2.6; p = 0.02). In the
      multivariate analysis, small tumors removed by EBR had a significantly lower LR
      risk. CONCLUSIONS: The LR risk of a single brain metastasis is influenced by
      biological factors (such as tumor volume) and treatments (such as the resection
      method). Early administration of postoperative WBRT may be particularly warranted
      when such negative tumor-related prognostic factors are noted or when treatment
      related ones such as PMR are unavoidable.

PMID- 20035576
TI  - Performance and training standards for endovascular ischemic stroke treatment.
AB  - Stroke is the third leading cause of death in the USA, Canada, Europe, and Japan.
      According to the American Heart Association and the American Stroke Association,
      there are now 750,000 new strokes that occur each year, resulting in 200,000
      deaths, or 1 of every 16 deaths, per year in the USA alone. Endovascular therapy
      for patients with acute ischemic stroke is an area of intense investigation. The
      American Stroke Association has given a qualified endorsement of intraarterial
      thrombolysis in selected patients. Intraarterial thrombolysis has been studied in
      two randomized trials and numerous case series. Although two devices have been
      granted FDA approval with an indication for mechanical stroke thrombectomy, none
      of these thrombectomy devices has demonstrated efficacy for the improvement of
      patient outcomes. The purpose of the present document is to define what
      constitutes adequate training to perform neuroendovascular procedures in patients
      with acute ischemic stroke and what performance standards should be adopted to
      assess outcomes. These guidelines have been written and approved by multiple
      neuroscience societies which historically have been directly involved in the
      medical, surgical and endovascular care of patients with acute stroke. The
      participating member organizations of the Neurovascular Coalition involved in the
      writing and endorsement of this document are the Society of NeuroInterventional
      Surgery, the American Academy of Neurology, the American Association of
      Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section,
      and the Society of Vascular & Interventional Neurology.

PMID- 20035575
TI  - Molecular mechanisms of microvascular failure in central nervous system injury-
      synergistic roles of NKCC1 and SUR1/TRPM4.
AB  - Microvascular failure largely underlies the damaging secondary events that
      accompany traumatic brain injury (TBI). Changes in capillary permeability result
      in the extravasation of extracellular fluid, inflammatory cells, and blood,
      thereby producing cerebral edema, inflammation, and progressive secondary
      hemorrhage (PSH). Recent work in rat models of TBI and stroke have implicated 2
      ion transport proteins expressed in brain endothelial cells as critical mediators
      of edema formation: the constitutively expressed Na(+)-K(+)-2Cl(-) cotransporter,
      NKCC1, and the trauma/ischemia-induced SUR1-regulated NC(Ca-ATP) (SUR1/TRPM4)
      channel. Whereas NKCC1 function requires adenosine 5'-triphosphate (ATP),
      activation of SUR1/TRPM4 occurs only after ATP depletion. This opposite
      dependence on intracellular ATP levels implies that one or the other mechanism
      will activate/deactivate as ATP concentrations rise and fall during periods of
      ischemia/reperfusion, resulting in continuous edema formation regardless of
      cellular energy status. Moreover, with critical ATP depletion, sustained opening
      of SUR1/TRPM4 channels results in the oncotic death of endothelial cells, leading
      to capillary fragmentation and PSH. Bumetanide and glibenclamide are 2 well
      characterized, safe, FDA-approved drugs that inhibit NKCC1 and the SUR1/TRPM4
      channel, respectively. When used alone, these drugs have provided documented
      beneficial effects in animal models of TBI- and ischemiaassociated cerebral edema
      and PSH. Given the mechanistic and temporal differences by which NKCC1 and the
      SUR1/TRPM4 channel contribute to the pathophysiological mechanisms of these
      events, combination therapy with bumetanide and glibenclamide may yield critical
      synergy in preventing injury-associated capillary failure.

PMID- 20035577
TI  - Abstracts of the 49th Annual National Institute of Mental Health (NIMH) New
      Clinical Drug Evaluation Unit (NCDEU) Meeting. Hollywood, Florida, USA. June 29
      July 2, 2009.

PMID- 20035579
TI  - A 6-week, randomized, double-blind, placebo-controlled study of the efficacy and
      safety of risperidone in adolescents with schizophrenia.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of two
      dose ranges of risperidone in adolescents with schizophrenia. METHODS: In a 6
      week, randomized, double-blind, placebo-controlled study, adolescents aged 13-17
      years with acute exacerbation of schizophrenia were randomized to placebo,
      flexible doses of risperidone 1-3 mg/day, or risperidone 4-6 mg/day. Assessments
      included the Positive and Negative Syndrome Scale (PANSS), clinical response (>
      or =20% reduction in PANSS total score), adverse event (AE) monitoring, and
      extrapyramidal symptom (EPS) scale ratings. RESULTS: A total of 160 subjects
      received placebo (n = 54), risperidone 1-3 mg/day (n = 55), or risperidone 4-6
      mg/day (n = 51). Significant improvements occurred in both risperidone groups
      versus placebo (p < 0.001) in PANSS total change scores (placebo, -8.9 [16.1];
      risperidone 1-3 mg, -21.3 [19.6]; risperidone 4-6 mg, -21.2 [18.3]) and clinical
      response rates (35%, 65%, 72%, respectively). Overall AE rates were more common
      in risperidone groups (75% and 76%) versus placebo (54%). Risperidone 4-6 mg/day
      had a higher incidence of extrapyramidal disorder, dizziness, and hypertonia than
      risperidone 1-3 mg. No prolactin-related AEs occurred. Overall EPS severity was
      low. CONCLUSIONS: Risperidone 1-3 mg/day and 4-6 mg/day were well tolerated and
      effective in adolescents experiencing acute episodes of schizophrenia. The
      benefit-risk profile suggests that a dose of 1-3 mg/day might be optimal for this
      population.

PMID- 20035580
TI  - Aripiprazole in children and adolescents with Tourette's disorder: an open-label
      safety and tolerability study.
AB  - OBJECTIVE: The aim of this study was to conduct a prospective safety and
      tolerability study of aripiprazole for the treatment of tics in children and
      adolescents with Tourette's disorder (TD). METHOD: Eleven subjects (10 males)
      with TD (age 9-19 years, mean 13.36, standard deviation [SD] 3.33) who did not
      respond or were unable to tolerate previous tic medication were treated with
      aripiprazole in an open-label, flexible-dosing study over 10 weeks. Tic severity
      was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical
      Global Impressions Scale for tics (CGI-Tics) at baseline and at follow-up.
      RESULTS: The mean (+/-SD) daily dose for aripiprazole was 4.5 +/- 3.0 mg. Mean
      (+/-SD) YGTSS Global Severity scores reduced from 61.82 +/- 13.49 at baseline to
      33.73 +/- 15.18 at end point; mean YGTSS total tic scores reduced from 28.18 +/-
      7.74 at baseline to 16.73 +/- 7.54 at end point. Mean (+/-SD) CGI-Tic severity
      scores reduced from 4.45 +/- 0.52 (moderate-marked) at baseline to 3.18 +/- 0.60
      (mild) at end point. On the CGI-Tic improvement scale, 10 (91%) subjects achieved
      1 ("very much improved") or 2 ("much improved") at end point. Most common adverse
      effects included appetite increase and weight gain in 5 subjects, mild
      extrapyramidal effects in 7 subjects, and headaches and tiredness/fatigue in 7
      subjects; 1 subject experienced akathisia and muscle cramps. CONCLUSION:
      Aripiprazole appears to be a safe and tolerable treatment in children and
      adolescents with TD that appears to reduce tics; it should be further
      investigated as a treatment option in controlled trials.

PMID- 20035581
TI  - Psychosocial functioning and health-related quality of life in children and
      adolescents treated with open-label ziprasidone for bipolar mania, schizophrenia,
      or schizoaffective disorder.
AB  - OBJECTIVE: The aim of this study was to examine global functioning, health
      related quality of life (HRQOL), and clinical outcome in children and adolescents
      with bipolar I disorder, schizophrenia, or schizoaffective disorder following
      ziprasidone treatment. METHODS: Sixty-three subjects (aged 10-17 years) received
      open-label ziprasidone, titrated from 10 to 40 mg twice a day (b.i.d.) (low-dose
      group) or from 20 to 80 mg b.i.d. (high-dose group); fixed doses were used until
      week 3, followed by flexible doses for 6 months. The Children's Global Assessment
      Scale (CGAS) characterized functional impairment at baseline and following
      treatment. The Child Health Questionnaire (CHQ) assessed HRQOL at baseline.
      RESULTS: Baseline CHQ showed greater impairment in psychosocial functioning than
      in physical health. Baseline mean CGAS scores were substantially below normal
      (i.e., <70), indicating functional impairment. Improvement in CGAS scores
      occurred as early as the first week of treatment. The low correlations between
      both CHQ and CGAS and the efficacy measures at baseline indicate that these
      scales measure different constructs. Nevertheless, there was good correlation
      between improvements in the CGAS and changes in Brief Psychiatric Rating Scale
      Anchored (BPRS-A) and Young Mania Rating Scale (YMRS) during ziprasidone
      treatment. CONCLUSION: CHQ and CGAS scales may be useful together with standard
      efficacy measures for children and adolescents with these disorders.

PMID- 20035582
TI  - Symptoms leading to a bipolar diagnosis: a phone survey of child and adolescent
      psychiatrists.
AB  - OBJECTIVE: We surveyed child and adolescent psychiatrists (CAPs) to characterize
      how they diagnose bipolar disorder (BPD) in children. METHODS: We approached by
      mail and then telephone 100 CAPs randomly sampled from five regions of the main
      professional organization of American CAPs; 53 CAPs were reached and agreed to
      participate. We asked about their training and practice setting, and asked them
      to name 10 symptoms indicative of BPD. We conducted descriptive analyses to
      determine how CAPs ranked symptoms, whether reports were consistent with
      Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision
      (DSM-IV-TR) criteria, and whether alternative symptom models might guide their
      decision making. RESULTS: CAPs considered lability, grandiosity, family history
      of BPD, aggression, and expansive or euphoric mood as the most important factors
      in diagnosing BPD. Only 21 (39.6%) CAPs reported sufficient symptoms to meet DSM
      criteria for BPD (DSM-Yes status). DSM-Yes status was associated with
      participants' region, less expertise (< or =10 years practicing child and
      adolescent psychiatry), and lower levels of self-reported confidence in their
      ability to diagnose BPD. CONCLUSIONS: CAPs vary in the symptoms they use to
      diagnose BPD, with most using a mixture of DSM and non-DSM symptoms. Expertise
      and confidence may lessen one's reliance on DSM criteria. Further studies are
      needed to understand CAPs' diagnostic decisions about BD and to develop
      interventions to support accurate diagnostic decision making and improve patient
      care.

PMID- 20035583
TI  - Effectiveness, safety, and tolerability of lisdexamfetamine dimesylate in
      children with attention-deficit/hyperactivity disorder: an open-label, dose
      optimization study.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness and safety of
      lisdexamfetamine dimesylate (LDX) in children with attention
      deficit/hyperactivity disorder (ADHD). METHOD: This was a 7-week, open-label
      study evaluating 20, 30, 40, 50, 60, or 70 mg/day LDX in 318 children aged 6-12
      years with ADHD. The ADHD Rating Scale IV (ADHD-RS-IV) was the primary efficacy
      assessment. Secondary measures included the Clinical Global Impressions
      Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), and
      Behavior Rating Inventory of Executive Function (BRIEF). Safety assessments
      included treatment-emergent adverse events (TEAEs), vital signs, and
      electrocardiograms. RESULTS: At end point, mean (standard deviation [SD])
      improvement from baseline in ADHD-RS-IV total score was 28.6 (10.9) (p < 0.0001).
      Most subjects (89.9%) were rated "improved" (i.e., CGI-I 1 or 2). Improvements
      from baseline were observed in the EESC total and subscale scores (p < or =
      0.0002). LDX treatment resulted in significant improvement on the Global
      Executive Composite, Behavioral Regulation, and Metacognition indices of the
      BRIEF (p < 0.0001). TEAEs (incidences > or =10%) were decreased appetite,
      decreased weight, irritability, insomnia, headache, upper abdominal pain, and
      initial insomnia. CONCLUSIONS: LDX was effective and generally well tolerated
      with a safety profile consistent with long-acting stimulant use. There was
      overall improvement in ADHD symptoms and executive function measures and no
      worsening of emotional expression measures. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00500071.

PMID- 20035584
TI  - Stimulant drug response in the predominantly inattentive and combined subtypes of
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: This study compared the methylphenidate (MPH) dose-response profiles
      of children with the Predominantly Inattentive (PI) and Combined (CB) subtypes of
      attention-deficit/hyperactivity disorder (ADHD). It is the first such study to
      enroll a sample comprised exclusively of children, all but one of whom had no
      prior exposure to ADHD medications. METHOD: The design was a double-blind
      crossover with 1-week exposures to placebo and low, medium, and high, fixed,
      three times daily (t.i.d.) dosage regimens of immediate-release MPH, administered
      in random order. Parents and teachers completed weekly behavioral questionnaires
      (Conners, Swanson, Kotkin, Agler, M-Flynn and Pelham Scale [SKAMP]) and a child
      psychiatrist provided weekly ratings of symptom severity (ADHD Rating Scale [ADHD
      RS]), side effects (Side Effects Rating Scale), and a Clinical Global Impressions
      Severity (CGI-S). In addition, laboratory measures of vigilance (Continuous
      Performance Test [CPT]) and resistance to cognitive interference (Stroop) were
      administered weekly. RESULTS: Twenty-five children (15 CB, 10 PI), who met
      rigorous diagnostic criteria for their ADHD subtype, completed the study. Groups
      did not differ on demographic variables or severity at baseline. Behavioral
      questionnaires and clinical ratings indicated significant improvement on MPH for
      both subtypes but no differences in response profiles of the two groups. Drug
      effects were predominantly linear for both subtypes. Effects of MPH were
      significant for the CPT, but not the Stroop, instrument with no differences
      between ADHD subtypes. CONCLUSIONS: Results support the clinical utility of MPH
      in the treatment of the PI subtype and provide no evidence of differences in
      response between the subtypes.

PMID- 20035585
TI  - Predictive factors for persistent use and compliance of immediate-release
      methylphenidate: a 36-month naturalistic study.
AB  - AIM: The objective of this study was to evaluate predictors of long-term
      adherence to treatment with methylphenidate (MPH). METHODS: A total of 134
      children (ages 4-16) with a diagnosis of attention-deficit/hyperactivity disorder
      (ADHD) determined by specific protocols, including a semistructured parent
      interview, Conners' Teacher/Parent Rating Scales, cognitive and learning
      evaluation, and child self-reports for anxiety and depression, were assessed
      monthly for up to 36 months. At the end of the study (36 months), three outcomes
      were evaluated (continuing medication, medication withdrawn due to functional
      remission, and medication withdrawn for other reasons including poor compliance).
      Outcomes were first analyzed by mean of the chi-squared test, Mann-Whitney-U
      test, or t-test, and predictive models were subsequently generated using Cox
      proportional hazards model analysis. Age, ADHD subtype, co-morbidity, cognitive
      functioning, side effects, and family and social characteristics were considered
      as independent variables. RESULTS: Thirty-six months after starting MPH, 62
      children (46%) were still on treatment, 32 (24%) had stopped MPH due to
      functional remission, and 40 (30%) had suspended MPH for other reasons. Within
      the last group, 20 suspended for poor compliance, 10 for decrease of efficacy, 5
      for side effects, and 5 because they entered in an atomoxetine clinical trial.
      The presence of associated disorders, younger age, female gender, and not living
      with both parents were predictors for continuing medication until end of the
      study (36 months); absence of associated disorders and older age were predictors
      of discontinuation medication due to functional remission before the end of
      study, older age, and hyperactive subtype were predictors of discontinuing
      medication for other reasons. CONCLUSION: Clinical outcome of ADHD treatment is
      heterogeneous: Specific clinical and social predictive parameters for long-term
      MPH use and compliance can be identified. An accurate tailoring of clinical
      intervention to the individual child appears crucial for good outcome.

PMID- 20035586
TI  - Adverse reactions to methylphenidate treatment for attention
      deficit/hyperactivity disorder: structure and associations with clinical
      characteristics and symptom control.
AB  - BACKGROUND: Methylphenidate (MPH)-related adverse events are well characterized.
      Their predictors and their relationship with therapeutic effects are less well
      understood. Here we examine these issues in relation to two long-acting
      formulations. METHOD: Comparison of Methylphenidates in the Analog Classroom
      Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing
      Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School
      protocol. Therapeutic effects were measured using direct observation, scores on a
      simple math productivity task and parent ratings. Parents also completed the
      Barkley Stimulant Side Effect Rating Scale (BSSERS). RESULTS: The BSSERS had six
      factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and
      aches. Treatment effects were seen only for emotionality (which improved) and
      sleep and appetite (which worsened). Adverse events were not predictable from
      personal and clinical characteristics of patients. Sleep/appetite adverse events
      were not associated with therapeutic effects. Improvements in attention
      deficit/hyperactivity disorder (ADHD) and emotionality were correlated.
      DISCUSSION: The results support a narrow conceptualization of MPH adverse events
      with problems restricted to appetite and sleep. These effects were not
      predictable on the basis of available information and may be due to an underlying
      mechanism rather distinct from those determining therapeutic effects.

PMID- 20035587
TI  - Measuring methylphenidate response in attention-deficit/hyperactvity disorder:
      how are laboratory classroom-based measures related to parent ratings?
AB  - BACKGROUND: Methylphenidate (MPH) is an efficacious and normally well-tolerated
      treatment for attention-deficit/hyperactivity disorder (ADHD). Although treatment
      effects are usually assessed using parent-rating scales, these can be
      supplemented by more objective methods. Here we examine the associations between
      ratings and one such method, assessments made across the day in the laboratory
      classroom. METHOD: Comparison of Methylphenidates in the Analog Classroom Setting
      (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym
      XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol.
      Therapeutic effects were measured using direct observation, scores on a simple
      math productivity task and parent ratings. RESULTS: Treatment effects were
      observed on all measures. Laboratory measures were correlated with each other,
      most strongly between Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP)
      inattention and Permanent Product Measure of Performance (PERMP). Parental
      ratings were correlated with classroom measures during the main morning period
      (1.5-4.5 hours after dosing) and to a lesser extent in the afternoon (6.0-7.5
      hours after dosing), but not, by and large, immediately after dosing or in the
      evening. The morning correlations seemed stronger for female than for male
      participants. DISCUSSION: The results suggest that parental ratings and direct
      observations tap different aspects of MPH response and that both may be required
      for comprehensive assessment.

PMID- 20035588
TI  - Differential effects of atomoxetine on executive functioning and lexical decision
      in attention-deficit/hyperactivity disorder and reading disorder.
AB  - OBJECTIVE: The effects of a promising pharmacological treatment for attention
      deficit/hyperactivity disorder (ADHD), atomoxetine, were studied on executive
      functions in both ADHD and reading disorder (RD) because earlier research
      demonstrated an overlap in executive functioning deficits in both disorders. In
      addition, the effects of atomoxetine were explored on lexical decision. METHODS:
      Sixteen children with ADHD, 20 children with ADHD + RD, 21 children with RD, and
      26 normal controls were enrolled in a randomized placebo-controlled crossover
      study. Children were measured on visuospatial working memory, inhibition, and
      lexical decision on the day of randomization and following two 28-day medication
      periods. RESULTS: Children with ADHD + RD showed improved visuospatial working
      memory performance and, to a lesser extent, improved inhibition following
      atomoxetine treatment compared to placebo. No differential effects of atomoxetine
      were found for lexical decision in comparison to placebo. In addition, no effects
      of atomoxetine were demonstrated in the ADHD and RD groups. CONCLUSION:
      Atomoxetine improved visuospatial working memory and to a lesser degree
      inhibition in children with ADHD + RD, which suggests differential developmental
      pathways for co-morbid ADHD + RD as compared to ADHD and RD alone. CLINICAL TRIAL
      REGISTRY: B4Z-MC-LYCK, NCT00191906;
      http://clinicaltrials.gov/ct2/show/NCT00191906.

PMID- 20035589
TI  - Atomoxetine and neuropsychological function in children with attention
      deficit/hyperactivity disorder: results of a pilot study.
AB  - This pilot longitudinal study using measures from parents and teachers evaluated
      the effects of flexible doses of atomoxetine (ATX) on neuropsychological and
      functional outcomes in 21 children with attention-deficit/hyperactivity disorder
      (ADHD) (mean age, 8.0 +/- 1.3 years; inattentive subtype, 71.4%; combined
      subtype, 28.6%). Among 16 children completing 6 months of ATX treatment,
      neuropsychological function measured by the NEPSY instrument found significant
      improvement from baseline in the memory and learning domain (p = 0.01); this
      change was also seen in an age- and sex-matched healthy control group (p =
      0.011). The patient group showed significant improvement on the Test of Everyday
      Attention (TEA-Ch) and parent and teacher versions of the Behavior Rating
      Inventory of Executive Function (BRIEF), which assess attentional and executive
      processes, respectively. Functional improvement was also observed on the Weiss
      Functional Impairment Rating Scale-Parent Report (WFIRS-P) and parent and teacher
      versions of the ADHD Rating Scale (ADHDRS-IV), and the investigator-rated
      Clinical Global Impressions-Severity (CGI-S) scale evidenced reductions in ADHD
      symptoms. These findings suggest that potential benefits of ATX treatment may
      extend beyond reduction of core ADHD symptoms to amelioration of some
      neuropsychological and functional deficits.

PMID- 20035590
TI  - Atomoxetine treatment in adolescents with attention-deficit/hyperactivity
      disorder.
AB  - INTRODUCTION: This study compared two atomoxetine titration dosing schedules and
      two atomoxetine maintenance doses for treating adolescent attention
      deficit/hyperactivity disorder (ADHD) inattention and hyperactivity/impulsivity.
      METHODS: Adolescents (N = 267) were randomized to a slow or fast titration
      schedule. Patients who responded continued on a 40-week maintenance treatment,
      randomized to either 0.8 or 1.4 mg/kg/day. RESULTS: During the acute period,
      significant benefit was demonstrated with both titration schedules on the ADHD
      Rating Scale total score. Although patients in both groups maintained benefit
      relative to week 0, statistically significant loss of benefit was found for
      patients maintained on 0.8 mg/kg/day but not on 1.4 mg/kg/day. A similar pattern
      was observed on the Clinical Global Impressions-ADHD-Severity scores and Life
      Participation Scale for ADHD-Child Version scores. Mean grades for most subjects
      improved for patients in both maintenance treatment groups although most
      improvements were not statistically significant. CONCLUSIONS: In adolescents with
      ADHD, treatment benefit at 8 weeks was better maintained long-term with 1.4
      mg/kg/day than with 0.8 mg/kg/day. Improvement in adaptive functioning and age
      appropriate developmental function was also demonstrated. Atomoxetine 0.8 and 1.4
      mg/kg/day were equally well tolerated. CLINICAL TRIALS REGISTRY: Maintenance of
      benefit with atomoxetine hydrochloride in adolescents with ADHD, NCT00191035.

PMID- 20035591
TI  - Early repolarization in young children with attention-deficit/hyperactivity
      disorder versus normal controls: a retrospective preliminary chart review study.
AB  - OBJECTIVE AND BACKGROUND: Early repolarization (ER), considered a common and
      benign electrocardiographic pattern on the surface 12-lead electrocardiogram
      (ECG), was recently found to be prevalent among patients with idiopathic
      ventricular fibrillation. It is also highly predominant in physically active
      young males. Reports on sudden cardiac death (SCD) of children and adolescents
      treated with psychotropic agents have raised concerns regarding the need for
      cardiovascular monitoring and risk stratification schedules. The rate of ER
      pattern has not been estimated in children with attention deficit/hyperactivity
      disorder (ADHD). Thus, in the present retrospective chart review study, we
      estimated the rate of ER pattern, as well as RR, QT, and QTc intervals, from ECG
      tracings of physically healthy children with ADHD versus physically and mentally
      healthy controls. METHODS: The ECG tracings of 50 children (aged 8.7 +/- 1.4
      years; 12 girls, 44 boys) diagnosed as suffering from ADHD were compared to 55
      physically and mentally healthy controls (aged 8.25 +/- 2.1 years; 20 girls, 35
      boys). ER was defined as an elevation of the QRS-ST junction (J point) of at
      least 0.1 mV from baseline with slurring or notching of the QRS complex, and
      assessed separately by two senior cardiologists who were blind to all other data
      relating to the study participants. RESULTS: The rate of ER pattern was
      significantly higher in ADHD children compared to normal controls (32% vs. 13%,
      respectively, P = 0.012; relative risk [RR] = 1.68, 95% confidence interval [CI]
      1.16-2.44), irrespective of stimulant treatment or gender. All other standard ECG
      measures (heart rate, QT and QTc intervals) were within normal range. CONCLUSION:
      The rate of ER in children with ADHD is significantly higher than in normal
      controls. Its clinical significance awaits further research.

PMID- 20035593
TI  - Cognitive function with long-term risperidone in children and adolescents with
      disruptive behavior disorder.
AB  - OBJECTIVE: The aim of this study was to evaluate cognitive effects from long-term
      risperidone treatment for disruptive behavior disorders (DBDs) in children and
      adolescents. METHODS: Patients 5-17 years old with DBDs and an intelligence
      quotient (IQ) > or =54 were randomized to flexibly dosed risperidone or placebo
      in a 6-month recurrence prevention trial. Cognitive function was assessed with a
      modified California Verbal Learning Test for Children (MVLT-C) and Continuous
      Performance Test (CPT), which assessed vigilance through computer testing with
      both an easy and a hard test. Somnolence was also evaluated throughout treatment.
      Clinically meaningful treatment effects were assessed as changes of > or =0.5 or
      > or =1.0 standard deviation (SD) from baseline. RESULTS: A total of 284 subjects
      participating in 6-month maintenance treatment had both baseline and end point
      cognition assessments and were included in this analysis. Significant
      improvements from baseline occurred in risperidone-treated subjects for CPT hard
      hit rates and discrimination ability (Pr) (p < 0.05 for both), and in placebo
      subjects for CPT easy false alarms rates (p < 0.001) and hard Pr (p < 0.05). Both
      the easy and hard CPTs correct mean response time worsened with placebo. The MVLT
      C short-delay free recall improved significantly for both risperidone and
      placebo. After adjusting for country, somnolence, age, IQ, and baseline scores,
      no significant differences were noted in cognition between treatment groups.
      Clinically meaningful changes were generally similar for risperidone and placebo
      patients. Mild to moderate somnolence occurred in only 2% of patients treated
      with either risperidone or placebo. The change in cognitive testing was not
      different in subjects experiencing somnolence as an adverse event (AE) compared
      with subjects not experiencing somnolence. CONCLUSIONS: Risperidone treatment
      resulted in no decline in cognitive function among children and adolescents.
      These results extend on previous results from risperidone studies in DBD in
      patients with lower IQ.

PMID- 20035594
TI  - Psychotropic drug use among Icelandic children: a nationwide population-based
      study.
AB  - OBJECTIVE: The aim of this study was to investigate psychotropic drug use among
      children in Iceland between 2003 and 2007. METHODS: A nationwide population-based
      drug use study covering the total pediatric population (ages 0-17) in Iceland.
      Information was obtained from the National Medicines Registry to calculate
      prevalence of use by year and psychotropic drug group; incidence by year,
      psychotropic drug group, child's age and sex, and medical specialty of
      prescriber; the most commonly used psychotropic chemical substances, off-label
      and unlicensed use and concomitant psychotropic drug use. RESULTS: The overall
      prevalence of psychotropic drug use was 48.7 per 1000 Icelandic children in 2007.
      Stimulants and antidepressants increased in prevalence from 2003 to 2007 and were
      the two most prevalent psychotropic drug groups, respectively, 28.4 and 23.4 per
      1000 children in 2007. A statistically significant trend of declining prevalence
      (p = 0.00013) and incidence (p = 0.0018) of antidepressant use occurred during
      the study period. Out of 21,986 psychotropic drugs dispensed in 2007, 25.4% were
      used off-label. CONCLUSIONS: With reference to reports from other European
      countries, the results indicate extensive psychotropic drug use among children in
      Iceland between 2003 and 2007. Further scrutiny is needed to assess the rationale
      behind this widespread use.

PMID- 20035592
TI  - Anxiety in boys with attention-deficit/hyperactivity disorder with and without
      chronic multiple tic disorder.
AB  - OBJECTIVE: This study examined the psychosocial and behavioral concomitants of
      anxiety in clinic-referred boys with attention-deficit/hyperactivity disorder
      (ADHD) with and without chronic multiple tic disorder (CMTD). METHOD: ADHD boys
      with (n = 65) and without (n = 94) CMTD were evaluated with measures of
      psychiatric symptoms, mental health risk factors, and academic and social
      performance. RESULTS: Boys with CMTD evidenced more severe anxiety and less
      social competence and were more likely to be living with only one biological
      parent than the ADHD Only group, but the magnitude of group differences was
      generally small. The severity of generalized anxiety, separation anxiety, social
      phobia, and obsessive-compulsive symptoms were uniquely associated with a
      different pattern of risk factors, and there was some evidence that these
      patterns differed for the two groups of boys. CONCLUSION: Boys with CMTD had a
      relatively more severe and complex pattern of anxiety that was associated with
      different clinical features, all of which suggests that ADHD plus CMTD might
      better be conceptualized as a distinct clinical entity from ADHD Only. However,
      findings from the extant literature are mixed, and therefore this remains a topic
      for further study.

PMID- 20035595
TI  - Psychotropic medication in children and adolescents in Germany: prevalence,
      indications, and psychopathological patterns.
AB  - OBJECTIVE: The aim of this study was to identify the "real-life" prevalence of
      psychotropic medications in children and adolescents in Germany and related
      behavioral and emotional problems. Data from the nationwide representative
      National German Health Interview and Examination Survey for Children and
      Adolescents (KiGGS) were analyzed. METHOD: A total of 17,450 subjects aged 0-17
      years from 167 communities were examined as part of the KiGGS in Germany between
      2003 and 2006 to determine their use of antidepressants, antipsychotics,
      anxiolytics, and sedatives within the 7 days prior to being interviewed.
      Medication use was assessed by a medical doctor who conducted a computer-assisted
      personal interview (CAPI) with the parents, and related emotional and behavioral
      problems were assessed using the Strength and Difficulties Questionnaire (SDQ).
      RESULTS: The overall prevalence for these medications was moderate (4.81/1000;
      95% confidence interval [CI], 3.70-6.26), but prevalence varied across the
      different classes of drugs (sedatives > antipsychotics > antidepressants >
      anxiolytics). Rates of off-label use were high for antipsychotics and
      antidepressants. About 30% of the medication, especially sedatives, was used
      without prescription. Subjects using psychotropic medication obtained higher
      scores in the screening for emotional or behavioral problems than the total
      sample, but 40% of the children did not show abnormal scores. CONCLUSION: The
      indication for antipsychotics was mostly behavioral symptomatology, while
      antidepressants were used for a wide variety of symptoms. The high proportion of
      children and adolescents using psychotropic medication with normal scores in the
      emotional and behavioral screening was remarkable. It cannot be determined
      whether in these cases low scores were related to improvement in symptoms or
      whether medication was being misused.

PMID- 20035596
TI  - Childhood onset diagnoses in a case series of teens at clinical high risk for
      psychosis.
AB  - REASONS: Schizophrenia is typically an adult neurodevelopmental disorder that has
      its antecedents in childhood and adolescence. Little is known about disorders
      "usually first diagnosed in infancy, childhood and adolescence" (e.g., childhood
      onset disorders) in "prodromal" teens at heightened clinical risk for psychotic
      disorder. MAIN FINDINGS: Childhood-onset disorders were prevalent in putatively
      prodromal teens, including anxiety and disruptive disorders, attention
      deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders.
      These may reflect developmental antecedents in psychotic disorders such as
      schizophrenia. KEY DATA AND STATISTICS: A case series of 9 teens (ages 13-17)
      identified as prodromal to psychosis were evaluated with the Kiddie Schedule for
      Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL).
      Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included
      ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9),
      conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder
      (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15-17). MAJOR
      CONCLUSIONS: An understanding of the childhood-onset disorders that occur in
      teens at risk for psychotic illnesses, such as schizophrenia, can shed light on
      the pathophysiology of schizophrenia and potentially inform early identification
      and intervention.

PMID- 20035597
TI  - Psychopharmacology news and views.

PMID- 20035598
TI  - Hyperprolactinemia in an adolescent with psychotic disorder on risperidone.

PMID- 20035600
TI  - Advances and perspectives on tissue repair and healing.

PMID- 20035601
TI  - Carbon dioxide (CO2) laser-assisted ablation of lumbar discal cyst.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical usefulness of CO2
      laser dissection in patients who had undergone lumbar discal cyst removal.
      METHODS: Clinical and radiological data were reviewed for 14 patients who
      underwent single lumbar level CO2 laser dissection followed by lumbar discal cyst
      removal between 2003 and 2008. They were followed up with plain radiographs, and
      their mean follow-up period was 20.1 months. RESULTS: Patients' mean hospital
      stay after operation was 3.5 days. Pain scores on a visual analog scale (VAS) for
      back and leg pain improved from a preoperative mean of 4.3 and 8.1 to
      postoperative 1.9 and 1.8, respectively (P<0.001). Clinical outcomes based on the
      Oswestry disability index (ODI) improved from a preoperative mean of 46.47% to
      14.81% postoperatively (P<0.001). CONCLUSION: Our results demonstrate that the
      CO2 laser could be a useful surgical tool for the surgical excision of lumbar
      discal cysts.

PMID- 20035602
TI  - Effect of erbium-doped yttrium aluminium garnet laser parameters on ablation
      capacity and morphology of primary dentin.
AB  - OBJECTIVE: To evaluate the ablation capacity of different energies and pulse
      repetition rates of an erbium-doped yttrium aluminium garnet (Er:YAG) laser on
      primary dentin by assessing mass loss and to analyze the surface morphology using
      scanning electron microscopy (SEM). BACKGROUND DATA: Previous studies have
      demonstrated the ability of the Er:YAG laser to ablate dentin substrate. METHODS:
      Forty-eight sound primary molars were bisected in the mesiodistal direction. The
      dentin surfaces were flattened, and initial mass (mg) was obtained. A 4-mm2 area
      was delimited. Specimens were randomly assigned to 12 groups according to the
      combination of energy (160, 200, 250, and 300 mJ) and pulse repetition rate (2,
      3, and 4 Hz). Er:YAG laser irradiation was performed for 20 s. After irradiation,
      the final mass was obtained, and specimens were prepared for SEM. The data
      obtained by subtracting the final mass from the initial mass were statistically
      analyzed using analysis of variance and Tukey test (alpha=0.05). RESULTS: The
      pulse repetition rate of 4 Hz provided greater mass loss, and it was different
      from 2 Hz and 3 HZ. The energy of 300 mJ resulted in greater mass loss, similar
      to 200 and 160 mJ. SEM micrographs showed dentinal tubule obliteration,
      structural alterations, and the presence of cracked areas in all specimens.
      CONCLUSION: The settings of 160, 200, and 250 mJ at 2 and 3 Hz promoted a good
      ablation rate with fewer surface alterations in primary dentin.

PMID- 20035603
TI  - The effects of helium-neon light therapy on healing of partial osteotomy of the
      tibia in streptozotocin induced diabetic rats.
AB  - OBJECTIVE: The effect of light therapy (LT) on surgically created partial
      osteotomy in streptozotocin (STZ)-induced diabetic rats was examined. BACKGROUND
      DATA: LT has been shown to enhance bone repair in healthy human and animal
      models. MATERIALS AND METHODS: Forty male rats were divided into groups 1 to 5.
      Diabetes was induced in rats of groups 1, 2, and 3 using an intraperitoneal
      injection of STZ. All diabetic rats were maintained for 30 days after STZ
      injection. Under general anesthesia and sterile conditions, a partial transversal
      standardized osteotomy was made in the mid-portion of the right tibia. The
      defects in groups 2, 3, and 5 were treated using a helium-neon (He-Ne) laser
      (632.8 nm, 10 mW, circular beam shape). Groups 1 and 4 were diabetic placebo and
      normal placebo groups, respectively. A dose of 369.4 J/cm2 for groups 2 and 5 and
      a dose of 66.8 J/cm2 for group 3 were applied three times a week. Six weeks after
      surgery, the right tibia was collected. The specimen was subjected to a three
      point bending test. RESULTS: LT with 369.4 J/cm2 energy density resulted in
      significantly greater bending stiffness in group 5 (41.8+/-5.2) than in groups 1
      (18.5+/-4.1), 2 (17.7+/-1.6), and 3 (11.5+/-4) (least significant difference
      (LSD) test, p<0.01, p<0.001, and p<0.001, respectively). LT with 369.4 J/cm2
      energy density resulted in a significantly higher stress load in group 5 (10+/
      0.4) than in groups 1 (4.9+/-1.5), 2 (5.7+/-0.52), and 3 (3.9+/-1.1) (LSD test,
      p<0.01, p<0.01, p<0.001, respectively). CONCLUSION: LT with a He-Ne laser in STZ
      induced diabetic rats did not enhance bone repair of a partial transversal
      standardized osteotomy.

PMID- 20035604
TI  - Potential antidepressant effect of infrared irradiation has seasonality.
AB  - OBJECTIVE: This study aimed to explore the seasonality of the antidepressant
      effect of infrared ray (IR) irradiation. BACKGROUND: IR has been found to reduce
      immobility in the forced swimming test (FST) in mice in the winter, suggesting an
      antidepressant effect. However, whether IR also possesses antidepressant effects
      in the summer remains questionable. METHODS: Fourteen mice were randomly assigned
      to the exposure group (n=7) and the control group (n=7). The mice in the exposure
      group received IR irradiation 60 minutes daily for six weeks in the summer. FSTs
      and tail suspension tests (TSTs) were administered to the two groups weekly. The
      mean immobility times in both tests were compared between and within groups.
      RESULTS: In both FST and TST, there were no significant differences among the
      mean immobility times overall. (Repeated measures two-way ANOVA: p=0.648, 0.574,
      respectively). Weekly comparison between groups revealed no significant
      differences at baseline (two-sample t-test: t12=-0.743, 0.341, respectively) or
      at the end of the study (p=0.924, 0.925, respectively). A repeated measures ANOVA
      showed no significant differences within the exposure group during the study
      period (p=0.602, 0.465, respectively). CONCLUSIONS: Taken together with the
      results of the previous study, the present results indicate that the
      antidepressant effect of IR irradiation has seasonality.

PMID- 20035605
TI  - Most important aspect of the treatment of severe burns is to close the wound as
      quickly as possible.

PMID- 20035606
TI  - Successful combination therapy for severe infantile hemangiomas: case report and
      literature search.
AB  - Infantile hemangiomas are common benign vascular tumors of infancy. Although the
      majority of uncomplicated hemangiomas involute spontaneously, rapid-growth
      lesions with complications need early active intervention. On the other hand,
      severe and complicated lesions can be difficult to treat. Recently, we
      successfully treated two cases of giant severe infantile facial hemangiomas using
      local application of bleomycin and pulsed dye laser along with systemic
      application of dexamethasone. Our results suggest that the multiple modalities of
      bleomycin, laser, and corticosteroid are a safe and effective approach for early
      therapeutic intervention of severe facial hemangiomas.

PMID- 20035607
TI  - Photomedicine and LLLT literature watch.

PMID- 20035609
TI  - The repair of critical-sized bone defects using expedited, autologous BMP-2 gene
      activated fat implants.
AB  - The repair of bone defects can be induced experimentally with bone morphogenetic
      protein-2 (BMP-2) producing fat-derived stem cells, but this ex vivo tissue
      engineering method requires the isolation and long-term culture of autologous
      cells. To develop an expedited bone repair strategy, we transferred BMP-2 cDNA
      directly to autologous fat tissue fragments that were held in culture for only 24
      h before implantation. We evaluated the ability of such gene-activated fat grafts
      to regenerate large segmental bone defects in rats. Fat tissue was harvested from
      2 of 35 male Fischer 344 rats used for this study. The fat tissue fragments were
      incubated with an adenoviral vector carrying the cDNA encoding either BMP-2 or
      green florescent protein (GFP), or they remained unmodified. According to their
      group, the segmental femoral bone defects of 33 rats were filled press fit with
      either BMP-2-activated fat tissue, GFP-transduced fat tissue, or unmodified fat
      tissue. Another control group remained untreated. Femora were evaluated by
      radiographs, microcomputed tomography, biomechanical torsional testing, and
      histology. Radiographically and histologically, 100% of the femora treated with
      BMP-2-activated fat grafts were bridged at 6 weeks after surgery. The femora of
      this group exceeded the bone volume and the biomechanical stability of intact,
      contralateral femora. Control defects receiving no treatment, unmodified fat
      tissue, or GFP-transduced fat were filled with fibrous or adipose tissue, as
      evaluated by histology. The use of BMP-2 gene-activated fat tissue grafts
      represents an expedited and effective bone repair strategy that does not require
      the extraction and expansion of stem cells.

PMID- 20035610
TI  - Primary orbital hydatid cyst in an elderly patient.
AB  - BACKGROUND: Orbital hydatidosis is rare, accounting for only 1% of all hydatid
      cysts. Herein we report a case and review the sparse literature. METHODS: Case
      report and review of pertinent literature. RESULTS: A 74-year-old farmer
      presented with progressive proptosis and loss of vision of the left eye.
      Evaluation revealed a hydatid cyst of the orbit. Orbital hydatidosis is usually
      unilateral and unaccompanied by cysts elsewhere in the body. Most affected are
      children and young adults. Although there is no gender predominance, orbital
      hydatidosis may affect the left eye preferentially. Onset is usually insidious
      over several months. Serologic testing is unreliable, and imaging by computed
      tomography or magnetic resonance imaging is now standard. Surgical resection is
      curative, but albendazole must be administered postoperatively if there is
      spillage intraoperatively. CONCLUSIONS: Hydatid cysts should be included in the
      differential diagnosis of unilateral proptosis in patients from regions where
      echinococcosis is endemic.

PMID- 20035611
TI  - The use of extended-interval aminoglycoside dosing strategies for the treatment
      of moderate-to-severe infections encountered in critically ill surgical patients.
AB  - BACKGROUND: Extended-interval dosing strategies have been developed to exploit
      the concentration-dependent bactericidal activity and time-dependent host
      toxicity associated with aminoglycoside the therapy. The ability of published
      extended-interval dosing nomograms to achieve optimal pharmacodynamic endpoints
      may be limited in certain critically ill surgical patients. METHODS: Review of
      pertinent English language literature. Presentation of descriptive, graded
      recommendations for extended-interval aminoglycoside dosing in critically ill
      surgical patients. RESULTS: Aminoglycoside dosing considerations in critically
      ill surgical patients should attempt to maximize the bacterial and host
      pharmacodynamic attributes of these agents. Empirically, extended-interval
      aminoglycoside doses proposed by published nomograms are reasonable for most
      patients; however, because of clinically meaningful variations in aminoglycoside
      pharmacokinetics, routine use of published extended-interval aminoglycoside
      dosing nomograms to determine an appropriate dosage interval is discouraged in
      many critically ill surgical patients. Critically ill surgical patients receiving
      extended-interval aminoglycoside dosages should undergo individualized
      pharmacokinetic analysis to characterize efficiently and more effectively plasma
      concentration-to-bacterial minimum inhibitory concentration (MIC) relationships
      and determine an appropriate dosing interval, considering site and severity of
      infection, plasma clearance, and the apparent post-antibiotic effect.
      CONCLUSIONS: The use of extended-interval aminoglycoside dosage regimens in
      critically ill surgical patients should be based on pharmacodynamic endpoints and
      patient-specific pharmacokinetic assessment.

PMID- 20035613
TI  - Microbead arrays for the analysis of ErbB receptor tyrosine kinase activation and
      dimerization in breast cancer cells.
AB  - Receptor tyrosine kinases (RTKs) in the ErbB family (EGFR, ErbB2, ErbB3, and
      ErbB4) are implicated in a variety of human malignancies. Accordingly,
      determination of both expression and activation (dimerization/heterodimerization
      and phosphorylation) of ErbB proteins is critical in defining their functional
      role in cancer. Efficient and comprehensive methods to study molecular functions
      of ErbB family of RTKs are needed not only for improvements in diagnostics but
      also for early screening of targeted drugs (eg, small molecule inhibitors and
      therapeutic antibodies). We report development of 3 multiplex microbead
      immunoassays for simultaneous detection of expression, protein-protein
      interactions, and phosphorylation of these RTKs. These novel multiplex
      immunoassays were used to study ErbB RTKs under different cell activation
      conditions in 2 breast cancer cell lines (MDA-MB-453 and MDA-MB-468) and an
      epidermoid cancer cell line (A431). The results were confirmed by
      immunoprecipitation/western blot. Importantly, the multiplex immunoassay
      facilitated time-course studies in these cell lines after cell activation with
      EGF and neuregulin, revealing the kinetics of phosphorylation of the ErbB family
      RTKs. This study demonstrates the utility of the Luminex(R) multiplex system as
      an efficient and comprehensive approach to study different aspects of molecular
      roles of these RTKs. Importantly, the study provides proof-of-concept for the
      utility of the multiplex microbead immunoassay approach for potential use in
      efficient, robust, and rapid screening of drugs, particularly those targeting
      functional aspects of these potent signaling molecules. In addition, the assays
      described here may be useful for cancer diagnostics and monitoring efficacy of
      therapy targeting the ErbB family of RTKs.

PMID- 20035614
TI  - A time-resolved fluorescence-resonance energy transfer assay for identifying
      inhibitors of hepatitis C virus core dimerization.
AB  - Binding of hepatitis C virus (HCV) RNA to core, the capsid protein, results in
      the formation of the nucleocapsid, the first step in the assembly of the viral
      particle. A novel assay was developed to discover small molecule inhibitors of
      core dimerization. This assay is based on time-resolved fluorescence resonance
      energy transfer (TR-FRET) between anti-tag antibodies labeled with either
      europium cryptate (Eu) or allophycocyanin (XL-665). The N-terminal 106-residue
      portion of core protein (core106) was tagged with either glutathione-S
      transferase (GST) or a Flag peptide. Tag-free core106 was selected as the
      reference inhibitor. The assay was used to screen the library of
      pharmacologically active compounds (LOPAC) consisting of 1,280 compounds and a
      2,240-compound library from the Center for Chemical Methodology and Library
      Development at Boston University (CMLD-BU). Ten of the 28 hits from the primary
      TR-FRET run were confirmed in a secondary amplified luminescent proximity
      homogeneous assay (ALPHA screen). One hit was further characterized by dose
      response analysis yielding an IC(50) of 9.3 microM. This 513 Da compound was
      shown to inhibit HCV production in cultured hepatoma cells.

PMID- 20035616
TI  - Evaluating the utility of a bioluminescent ADP-detecting assay for lipid kinases.
AB  - The lipid second messengers phosphatidylinositol-3,4,5-trisphosphate
      (PtdIns(3,4,5)P3) and sphingosine 1-phosphate (S1P) are well recognized to play
      important roles in a variety of cellular processes, including cell proliferation,
      apoptosis, metabolism, and migration. Disruption of lipid signaling pathways
      often leads to human cancers, making lipid kinases attractive drug targets. In
      order to develop novel drugs against these enzymes, an assay that monitors their
      activity and amenable to high-throughput scale for screening large number of
      compounds is essential. The newly developed ADP-Glo assay is such an assay that
      measures kinase activity of lipid kinases by detecting the formation of ADP using
      a highly robust and sensitive bioluminescence approach. We evaluated this
      technology for studying lipid kinases, class I PI3 kinases, and sphingosine
      kinases and we show that the assay exhibits good tolerance to different lipids
      substrates. It generates kinetic parameters for substrates and inhibitors similar
      to those reported in the literature using other published assay formats. The
      sensitivity and robustness of this assay allow the detection of 5% of substrate
      conversion with Z' values >0.7 making it attractive for high-throughput screening
      (HTS) applications. It is noteworthy that ADP-Glo assay addresses the need for a
      single integrated platform to comprehensively measure all classes of lipid and
      protein kinases. The selected inhibitors of lipid kinases can be screened against
      the panel of desired protein kinases, making ADP-Glo assay a simple, inexpensive
      platform for HTS and profiling of lipid kinases.

PMID- 20035615
TI  - High-throughput multiplex flow cytometry screening for botulinum neurotoxin type
      a light chain protease inhibitors.
AB  - Given their medical importance, proteases have been studied by diverse approaches
      and screened for small molecule protease inhibitors. Here, we present a
      multiplexed microsphere-based protease assay that uses high-throughput flow
      cytometry to screen for inhibitors of the light chain protease of botulinum
      neurotoxin type A (BoNTALC). Our assay uses a full-length substrate and several
      deletion mutants screened in parallel to identify small molecule inhibitors. The
      use of multiplex flow cytometry has the advantage of using full-length
      substrates, which contain already identified distal-binding elements for the
      BoNTALC, and could lead to a new class of BoNTALC inhibitors. In this study, we
      have screened 880 off patent drugs and bioavailable compounds to identify ebselen
      as an in vitro inhibitor of BoNTALC. This discovery demonstrates the validity of
      our microsphere-based approach and illustrates its potential for high-throughput
      screening for inhibitors of proteases in general.

PMID- 20035617
TI  - A software framework enabling analysis of plate-based flow cytometry data for
      high-throughput screening.
AB  - Flow cytometry (FCM) is an important technology with a broad spectrum of
      applications ranging from basic research to clinical diagnostics. In a typical
      FCM experiment, thousands of cells are queried with respect to size, shape, and
      abundance of multiple cell surface antigens. Recent advances in FCM techniques
      and instrumentation have enabled researchers to raise the throughput of
      experimentation dramatically. However, data analysis has remained a time
      consuming activity requiring significant manual intervention for gating as well
      as for overall data reduction and interpretation. Presented in this article is a
      novel, algorithmically flexible, internally developed, software framework for the
      analysis of plate-based FCM data for high-throughput screening (HTS). Utilizing a
      post-treatment pooling strategy, >87,000 individual wells representing over
      240,000 compounds were automatically gated, percent of control (POC) calculated,
      results assembled, deconvolved, and sorted, allowing researchers to visually
      assess wells of interest in minutes.

PMID- 20035618
TI  - An interview with Martin Rosenberg, Ph.D. Interviewed by Vicki Glaser.

PMID- 20035619
TI  - Outcome prediction in mild traumatic brain injury: age and clinical variables are
      stronger predictors than CT abnormalities.
AB  - Mild traumatic brain injury (mTBI) is a common heterogeneous neurological
      disorder with a wide range of possible clinical outcomes. Accurate prediction of
      outcome is desirable for optimal treatment. This study aimed both to identify the
      demographic, clinical, and computed tomographic (CT) characteristics associated
      with unfavorable outcome at 6 months after mTBI, and to design a prediction model
      for application in daily practice. All consecutive mTBI patients (Glasgow Coma
      Scale [GCS] score: 13-15) admitted to our hospital who were age 16 or older were
      included during an 8-year period as part of the prospective Radboud University
      Brain Injury Cohort Study (RUBICS). Outcome was assessed at 6 months post-trauma
      using the Glasgow Outcome Scale-Extended (GOSE), dichotomized into unfavorable
      (GOSE score 1-6) and favorable (GOSE score 7-8) outcome groups. The predictive
      value of several variables was determined using multivariate binary logistic
      regression analysis. We included 2784 mTBI patients and found CT abnormalities in
      20.7% of the 1999 patients that underwent a head CT. Age, extracranial injuries,
      and day-of-injury alcohol intoxication proved to be the strongest outcome
      predictors. The presence of facial fractures and the number of hemorrhagic
      contusions emerged as CT predictors. Furthermore, we showed that the predictive
      value of a scheme based on a modified Injury Severity Score (ISS), alcohol
      intoxication, and age equalled the value of one that also included CT
      characteristics. In fact, it exceeded one that was based on CT characteristics
      alone. We conclude that, although valuable for the identification of the
      individual mTBI patient at risk for deterioration and eventual neurosurgical
      intervention, CT characteristics are imperfect predictors of outcome after mTBI.

PMID- 20035620
TI  - Overexpression of beta-arrestin 2 in peripheral blood mononuclear cells of
      patients with cryptococcal meningitis.
AB  - Cryptococcal meningitis is often associated with elevated IL-10 levels, which
      suggest a dysregulation in the antifungal immune response. beta-Arrestin 2 plays
      a major role in desensitization of G-protein-coupled receptors involved in the
      immune responses, provides a scaffolding platform for modification of many signal
      transduction proteins, and binds Src and MAP kinases family members. This study
      compared the levels of beta-arrestin 2 mRNA and protein in peripheral blood
      mononuclear cells (PBMC) of patients with cryptococcal meningitis detected. The
      interferon-gamma (IFN-gamma) serum concentration was determined with enzyme
      linked immunosorbent assay (ELISA) to reveal its relationship with beta-arrestin
      2. The effect of modulation of beta-arrestin 2 on cytotoxic activity against
      Cryptococcus was explored via transfection and interference of beta-arrestin 2.
      PBMCs of patients with cryptococcal meningitis exhibited significantly elevated
      levels of beta-arrestin 2 and a positive correlation between beta-arrestin 2 and
      IL-10 levels existed in patients' serum, but a negative correlation was found
      between beta-arrestin 2 and IFN-gamma expression. In conclusion, elevated
      expression of beta-arrestin 2 in PBMCs of patients with cryptococcal meningitis
      correlated with a reduced cytotoxic activity against Cryptococcus. This study
      suggests that reduced beta-arrestin 2 mRNA levels or inhibition of beta-arrestin
      2 activity may augment INF-gamma production, and ultimately, the anti
      Cryptococcus immune response of infected patients.

PMID- 20035621
TI  - Nitric oxide stimulates interleukin-6 production in skeletal myotubes.
AB  - Strenuous exercise leads to the up-regulation of interleukin-6 (IL-6) production
      and enhanced nitric oxide (NO) release within the contracting skeletal muscles.
      In this study, we investigated whether NO regulates IL-6 production in C2C12
      myotubes. These cells exhibited a concentration-dependent increase in IL-6
      production upon stimulation with NO donors (Z)-1-[N-(2-aminoethyl)-N-(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), (Z)-1-[N-(3
      aminopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate), and
      sodium nitroprusside (SNP). This treatment did not alter cGMP levels nor did the
      soluble guanylyl cyclase (sGC) inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1
      one(ODQ), alter this response. The NO-independent sGC activator 5-cyclopropyl-2
      [1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY41
      2272) and cyclic guanosine monophosphate (cGMP) analog 8Br-cGMP failed to induce
      IL-6 production. Upon exposure to NO donors, we observed an increase in Erk1/2
      and p38 MAPK phosphorylation but not in SAPK/JNK. In addition, NO-induced IL-6
      release was inhibited in a concentration-dependent fashion by the MEK1/2
      inhibitor PD98059 and the p38 MAPK inhibitor SB203580 but not by the SAPK/JNK
      inhibitor SP600125. We conclude that NO-stimulated IL-6 production in
      differentiated C2C12 myotubes is cGMP-independent and mediated by activation of
      MAPK pathways.

PMID- 20035622
TI  - Assessment of endometrial and ovarian characteristics using three dimensional
      power Doppler ultrasound to predict response in frozen embryo transfer cycles.
AB  - OBJECTIVE: To evaluate whether endometrial or ovarian parameters as measured
      using 3D power Doppler ultrasound would predict the outcome in frozen embryo
      transfer (FET) cycles. METHODS: Thirty women with no known gynecological
      pathology undergoing FET were recruited. The FET was carried out in the natural
      menstrual cycle 3-4 days after the first positive LH test result. Blood samples
      for hormonal analysis were collected, and three-dimensional (3D) ultrasonographic
      examination was performed on the day of the FET and repeated with analysis of the
      total hCG one week later. RESULTS: The demographic, clinical, and embryological
      characteristics were similar between the pregnant (15/30) and nonpregnant groups
      (15/30). There were no differences between the groups in
      endometrial/subendometrial thickness, volume, or vascularization index (VI). The
      endometrial triple-line pattern was more often present in the pregnant group on
      the day of the FET (93.3% vs. 40.0%, 95% CI 25.5-81.2%). No differences in the
      ovaries were observed on the day of the FET. At the second visit, the triple-line
      pattern was still more often present in those patients who had conceived (91.7%
      vs. 42.9%, 95% CI 18.5-79.1%), and their corpus luteum was more active as judged
      by the rise in 17-hydroxyprogesterone and estradiol levels. No differences were
      observed in the dominant ovarian vasculature. CONCLUSIONS: According to our
      results, measurement of power Doppler indices using 3D ultrasound on the day of
      the FET does not provide any additional information concerning the outcome of the
      cycle. The existence of the triple-line pattern on the day of the FET seems to be
      a prognostic sign of a prosperous outcome after FET. The dominant ovary in the
      pregnant group seems to be already activated one week after the FET.

PMID- 20035623
TI  - De-institutionalisation and trans-institutionalisation - changing trends of
      inpatient care in Norwegian mental health institutions 1950-2007.
AB  - BACKGROUND: Over the last decades mental health services in most industrialised
      countries have been characterised by de-institutionalisation and different kinds
      of redistribution of patients. This article will examine the historical trends in
      Norway over the period 1950-2007, identify the patterns of change in service
      settings and discuss why the mental health services have been dramatically
      transformed in less than sixty years. METHODS: The presentation of the trends in
      the Norwegian mental health services and the outline of the major changes in the
      patterns of inpatient care over the period 1950-2007 is founded on five
      indicators: The average inpatient population, the number of discharges during a
      year, the average length of stay, the number of beds or places, and the occupancy
      rate (average inpatient population/beds).  Data are reported by institutional
      setting. Multiple sources of data are used. In some cases it has been necessary
      to interpolate data due to missing data. RESULTS: New categories of institutions
      were established and closed during the 57 years period. De-hospitalisation
      started in Norway in the early 1970s, de-institutionalisation in general 15 years
      later. Six distinct periods are identified: The asylum period (-1955),
      institutionalisation and trans-institutionalisation (1955-65), stabilisation and
      onset of de-hospitalisation (1965-75), de-hospitalisation (1975-87), from nursing
      homes to community-based services (1988-98), and the national mental health
      program (1999-2007). There has been a significant reduction in the number of beds
      and in the average in-patient population. The average length of stay in
      institutions has been continuously reduced since 1955. The number of patients
      actually treated in psychiatric institutions has increased significantly.
      Accessibility, quality of care and treatment for most patients has improved
      during the period. The mental health system in Norway has recently been evaluated
      as better than the systems in USA, England and Canada. CONCLUSIONS: De
      institutionalisation means fewer beds but not fewer patients treated, neither in
      institutions in general nor in psychiatric hospitals. The periods represent
      different kinds of de-, trans-, and even re-institutionalisation. Expansion of
      the welfare state, increased professional focus on active treatment and increased
      focus on patients' preferences are the factors that best explain de
      institutionalisation in Norway.

PMID- 20035624
TI  - Flux Design: In silico design of cell factories based on correlation of pathway
      fluxes to desired properties.
AB  - BACKGROUND: The identification of genetic target genes is a key step for rational
      engineering of production strains towards bio-based chemicals, fuels or
      therapeutics. This is often a difficult task, because superior production
      performance typically requires a combination of multiple targets, whereby the
      complex metabolic networks complicate straightforward identification. Recent
      attempts towards target prediction mainly focus on the prediction of gene
      deletion targets and therefore can cover only a part of genetic modifications
      proven valuable in metabolic engineering. Efficient in silico methods for
      simultaneous genome-scale identification of targets to be amplified or deleted
      are still lacking. RESULTS: Here we propose the identification of targets via
      flux correlation to a chosen objective flux as approach towards improved
      biotechnological production strains with optimally designed fluxes. The approach,
      we name Flux Design, computes elementary modes and, by search through the modes,
      identifies targets to be amplified (positive correlation) or down-regulated
      (negative correlation). Supported by statistical evaluation, a target potential
      is attributed to the identified reactions in a quantitative manner. Based on
      systems-wide models of the industrial microorganisms Corynebacterium glutamicum
      and Aspergillus niger, up to more than 20,000 modes were obtained for each case,
      differing strongly in production performance and intracellular fluxes. For lysine
      production in C. glutamicum the identified targets nicely matched with reported
      successful metabolic engineering strategies. In addition, simulations revealed
      insights, e.g. into the flexibility of energy metabolism. For enzyme production
      in A.niger flux correlation analysis suggested a number of targets, including non
      obvious ones. Hereby, the relevance of most targets depended on the metabolic
      state of the cell and also on the carbon source. CONCLUSIONS: Objective flux
      correlation analysis provided a detailed insight into the metabolic networks of
      industrially relevant prokaryotic and eukaryotic microorganisms. It was shown
      that capacity, pathway usage, and relevant genetic targets for optimal production
      partly depend on the network structure and the metabolic state of the cell which
      should be considered in future metabolic engineering strategies. The presented
      strategy can be generally used to identify priority sorted amplification and
      deletion targets for metabolic engineering purposes under various conditions and
      thus displays a useful strategy to be incorporated into efficient strain and
      bioprocess optimization.

PMID- 20035625
TI  - Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering
      LRP16 in cytoplasm.
AB  - BACKGROUND: Oncogenesis in breast cancer is often associated with excess estrogen
      receptor alpha(ERalpha) activation and overexpression of its coactivators. LRP16
      is both an ERalpha target gene and an ERalpha coactivator, and plays a crucial
      role in ERalpha activation and proliferation of MCF-7 breast cancer cells.
      However, the regulation of the functional availability of this coactivator
      protein is not yet clear. RESULTS: Yeast two-hybrid screening, GST pulldown and
      coimmunoprecipitation (CoIP) identified the cytoplasmic intermediate filament
      protein keratin 18 (K18) as a novel LRP16-interacting protein. Fluorescence
      analysis revealed that GFP-tagged LRP16 was primarily localized in the nuclei of
      mock-transfected MCF-7 cells but was predominantly present in the cytoplasm of
      K18-transfected cells. Immunoblotting analysis demonstrated that the amount of
      cytoplasmic LRP16 was markedly increased in cells overexpressing K18 whereas
      nuclear levels were depressed. Conversely, knockdown of endogenous K18 expression
      in MCF-7 cells significantly decreased the cytoplasmic levels of LRP16 and
      increased levels in the nucleus. CoIP failed to detect any interaction between
      K18 and ERalpha, but ectopic expression of K18 in MCF-7 cells significantly
      blunted the association of LRP16 with ERalpha, attenuated ERalpha-activated
      reporter gene activity, and decreased estrogen-stimulated target gene expression
      by inhibiting ERalpha recruitment to DNA. Furthermore, BrdU incorporation assays
      revealed that K18 overexpression blunted the estrogen-stimulated increase of S
      phase entry of MCF-7 cells. By contrast, knockdown of K18 in MCF-7 cells
      significantly increased ERalpha-mediated signaling and promoted cell cycle
      progression. CONCLUSIONS: K18 can effectively associate with and sequester LRP16
      in the cytoplasm, thus attenuating the final output of ERalpha-mediated signaling
      and estrogen-stimulated cell cycle progression of MCF-7 breast cancer cells. Loss
      of K18 increases the functional availability of LRP16 to ERalpha and promotes the
      proliferation of ERalpha-positive breast tumor cells. K18 plays an important
      functional role in regulating the ERalpha signaling pathway.

PMID- 20035626
TI  - Expression of the costimulatory molecule B7-H3 is associated with prolonged
      survival in human pancreatic cancer.
AB  - BACKGROUND: Costimulatory signaling has been implicated as a potential regulator
      of antitumor immunity in various human cancers. In contrast to the negative
      prognostic value of aberrant B7-H1 expression by pancreatic cancer cells, the
      role of B7-H3 is still unknown. Therefore, we investigated the expression pattern
      and clinical significance of B7-H3 expression in human pancreatic cancer.
      METHODS: B7-H3 expression was evaluated by immunohistochemistry in 68 patients
      with pancreatic cancer who underwent surgical tumor resection. Expression data
      was correlated with clinicopathologic features and with the number of tumor
      infiltrating T cells. RESULTS: B7-H3 expression was significantly upregulated in
      pancreatic cancer compared to normal pancreas (p < 0.05). In 60 of 68 examined
      tumors B7-H3 protein was detectable in pancreatic cancer cells. Patients with
      high tumor B7-H3 levels had a significantly better postoperative prognosis than
      patients with low tumor B7-H3 levels (p = 0.0067). Furthermore, tumor B7-H3
      expression significantly correlated with the number of tumor-infiltrating CD8+ T
      cells (p = 0.018). CONCLUSION: We demonstrate for the first time that B7-H3 is
      abundantly expressed in pancreatic cancer and that tumor-associated B7-H3
      expression significantly correlates with prolonged postoperative survival. Our
      findings suggest that B7-H3 might play an important role as a potential
      stimulator of antitumor immune response in pancreatic cancer.

PMID- 20035628
TI  - ITS2 secondary structure improves phylogeny estimation in a radiation of blue
      butterflies of the subgenus Agrodiaetus (Lepidoptera: Lycaenidae: Polyommatus ).
AB  - BACKGROUND: Current molecular phylogenetic studies of Lepidoptera and most other
      arthropods are predominantly based on mitochondrial genes and a limited number of
      nuclear genes. The nuclear genes, however, generally do not provide sufficient
      information for young radiations. ITS2 , which has proven to be an excellent
      nuclear marker for similarly aged radiations in other organisms like fungi and
      plants, is only rarely used for phylogeny estimation in arthropods, although
      universal primers exist. This is partly due to difficulties in the alignment of
      ITS2 sequences in more distant taxa. The present study uses ITS2 secondary
      structure information to elucidate the phylogeny of a species-rich young
      radiation of arthropods, the butterfly subgenus Agrodiaetus. One aim is to
      evaluate the efficiency of ITS2 to resolve the phylogeny of the subgenus in
      comparison with COI , the most important mitochondrial marker in arthropods.
      Furthermore, we assess the use of compensatory base changes in ITS2 for the
      delimitation of species and discuss the prospects of ITS2 as a nuclear marker for
      barcoding studies. RESULTS: In the butterfly family Lycaenidae, ITS2 secondary
      structure enabled us to successfully align sequences of different subtribes in
      Polyommatini and produce a Profile Neighbour Joining tree of this tribe, the
      resolution of which is comparable to phylogenetic trees obtained with COI+COII .
      The subgenus Agrodiaetus comprises 6 major clades which are in agreement with COI
      analyses. A dispersal-vicariance analysis (DIVA) traced the origin of most
      Agrodiaetus clades to separate biogeographical areas in the region encompassing
      Eastern Anatolia, Transcaucasia and Iran. CONCLUSIONS: With the inclusion of
      secondary structure information, ITS2 appears to be a suitable nuclear marker to
      infer the phylogeny of young radiations, as well as more distantly related genera
      within a diverse arthropod family. Its phylogenetic signal is comparable to the
      mitochondrial marker COI . Compensatory base changes are very rare within
      Polyommatini and cannot be used for species delimitation. The implementation of
      secondary structure information into character-based phylogenetic methods is
      suggested to further improve the versatility of this marker in phylogenetic
      studies.

PMID- 20035629
TI  - PRNP variation in UK sporadic and variant Creutzfeldt Jakob disease highlights
      genetic risk factors and a novel non-synonymous polymorphism.
AB  - BACKGROUND: Genetic analysis of the human prion protein gene (PRNP) in suspect
      cases of Creutzfeldt-Jakob disease (CJD) is necessary for accurate diagnosis and
      case classification. Previous publications on the genetic variation at the PRNP
      locus have highlighted the presence of numerous polymorphisms, in addition to the
      well recognised one at codon 129, with significant variability between
      geographically distinct populations. It is therefore of interest to consider
      their influence on susceptibility or the clinico-pathological disease phenotype.
      This study aimed to characterise the frequency and effect of PRNP open reading
      frame polymorphisms other than codon 129 in both disease and control samples
      sourced from the United Kingdom population. METHODS: DNA was extracted from blood
      samples and genetic data obtained by full sequence analysis of the prion protein
      gene or by restriction fragment length polymorphism analysis using restriction
      enzymes specific to the gene polymorphism under investigation. RESULTS: 147 of
      166 confirmed cases of variant CJD (vCJD) in the UK have had PRNP codon 129
      genotyping and all are methionine homozygous at codon 129; 118 have had full PRNP
      gene sequencing. Of the latter, 5 cases have shown other polymorphic loci: at
      codon 219 (2, 1.69%), at codon 202 (2, 1.69%), and a 24 bp deletion in the
      octapeptide repeat region (1, 0.85%). E219K and D202D were not found in sporadic
      CJD (sCJD) cases and therefore may represent genetic risk factors for
      vCJD.Genetic analysis of 309 confirmed UK sCJD patients showed codon 129 genotype
      frequencies of MM: 59.5% (n = 184), MV: 21.4% (n = 66), and VV: 19.1% (n = 59).
      Thirteen (4.2%) had the A117A polymorphism, one of which also had the P68P
      polymorphism, four (1.3%) had a 24 bp deletion, and a single patient had a novel
      missense variation at codon 167. As the phenotype of this latter case is similar
      to sCJD and in the absence of a family history of CJD, it is unknown whether this
      is a form of genetic CJD, or simply a neutral polymorphism. CONCLUSIONS: This
      analysis of PRNP genetic variation in UK CJD patients is the first to show a
      comprehensive comparison with healthy individuals (n = 970) from the same
      population, who were genotyped for the three most common variations (codon 129,
      codon 117, and 24 bp deletion). These latter two genetic variations were equally
      frequent in UK sCJD or vCJD cases and a normal (healthy blood donor) UK
      population.

PMID- 20035627
TI  - ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and
      Alzheimer's pathology.
AB  - The endoplasmic reticulum (ER) is involved in several crucial cellular functions,
      e.g. protein folding and quality control, maintenance of Ca2+ balance, and
      cholesterol synthesis. Many genetic and environmental insults can disturb the
      function of ER and induce ER stress. ER contains three branches of stress
      sensors, i.e. IRE1, PERK and ATF6 transducers, which recognize the misfolding of
      proteins in ER and activate a complex signaling network to generate the unfolded
      protein response (UPR). Alzheimer's disease (AD) is a progressive
      neurodegenerative disorder involving misfolding and aggregation of proteins in
      conjunction with prolonged cellular stress, e.g. in redox regulation and Ca2+
      homeostasis. Emerging evidence indicates that the UPR is activated in neurons but
      not in glial cells in AD brains. Neurons display pPERK, peIF2alpha and pIRE1alpha
      immunostaining along with abundant diffuse staining of phosphorylated tau
      protein. Recent studies have demonstrated that ER stress can also induce an
      inflammatory response via different UPR transducers. The most potent pathways are
      IRE1-TRAF2, PERK-eIF2alpha, PERK-GSK-3, ATF6-CREBH, as well as inflammatory
      caspase-induced signaling pathways. We will describe the mechanisms which could
      link the ER stress of neurons to the activation of the inflammatory response and
      the evolution of pathological changes in AD.

PMID- 20035630
TI  - Improved quality monitoring of multi-center acupuncture clinical trials in China.
AB  - BACKGROUND: In 2007, the Chinese Science Division of the State Administration of
      Traditional Chinese Medicine(TCM) convened a special conference to discuss
      quality control for TCM clinical research. Control and assurance standards were
      established to guarantee the quality of clinical research. This paper provides
      practical guidelines for implementing strict and reproducible quality control for
      acupuncture randomized controlled trials (RCTs). METHODS: A standard quality
      control program (QCP) was established to monitor the quality of acupuncture
      trials. Case report forms were designed; qualified investigators, study personnel
      and data management personnel were trained. Monitors, who were directly appointed
      by the project leader, completed the quality control programs. They guaranteed
      data accuracy and prevented or detected protocol violations. Clinical centers and
      clinicians were audited, the randomization system of the centers was inspected,
      and the treatment processes were audited as well. In addition, the case report
      forms were reviewed for completeness and internal consistency, the eligibility
      and validity of the patients in the study was verified, and data was monitored
      for compliance and accuracy. RESULTS AND DISCUSSION: The monitors complete their
      reports and submit it to quality assurance and the sponsors. Recommendations and
      suggestions are made for improving performance. By holding regular meetings to
      discuss improvements in monitoring standards, the monitors can improve quality
      and efficiency. CONCLUSIONS: Supplementing and improving the existed guidelines
      for quality monitoring will ensure that large multi-centre acupuncture clinical
      trials will be considered as valid and scientifically stringent as pharmaceutical
      clinical trials. It will also develop academic excellence and further promote the
      international recognition of acupuncture.

PMID- 20035631
TI  - Sympatric ecological speciation meets pyrosequencing: sampling the transcriptome
      of the apple maggot Rhagoletis pomonella.
AB  - BACKGROUND: The full power of modern genetics has been applied to the study of
      speciation in only a small handful of genetic model species--all of which
      speciated allopatrically. Here we report the first large expressed sequence tag
      (EST) study of a candidate for ecological sympatric speciation, the apple maggot
      Rhagoletis pomonella, using massively parallel pyrosequencing on the Roche 454
      FLX platform. To maximize transcript diversity we created and sequenced separate
      libraries from larvae, pupae, adult heads, and headless adult bodies. RESULTS: We
      obtained 239,531 sequences which assembled into 24,373 contigs. A total of 6810
      unique protein coding genes were identified among the contigs and long
      singletons, corresponding to 48% of all known Drosophila melanogaster protein
      coding genes. Their distribution across GO classes suggests that we have obtained
      a representative sample of the transcriptome. Among these sequences are many
      candidates for potential R. pomonella "speciation genes" (or "barrier genes")
      such as those controlling chemosensory and life-history timing processes.
      Furthermore, we identified important marker loci including more than 40,000
      single nucleotide polymorphisms (SNPs) and over 100 microsatellites. An initial
      search for SNPs at which the apple and hawthorn host races differ suggested at
      least 75 loci warranting further work. We also determined that developmental
      expression differences remained even after normalization; transcripts expected to
      show different expression levels between larvae and pupae in D. melanogaster also
      did so in R. pomonella. Preliminary comparative analysis of transcript presences
      and absences revealed evidence of gene loss in Drosophila and gain in the higher
      dipteran clade Schizophora. CONCLUSIONS: These data provide a much needed
      resource for exploring mechanisms of divergence in this important model for
      sympatric ecological speciation. Our description of ESTs from a substantial
      portion of the R. pomonella transcriptome will facilitate future functional
      studies of candidate genes for olfaction and diapause-related life history
      timing, and will enable large scale expression studies. Similarly, the
      identification of new SNP and microsatellite markers will facilitate future
      population and quantitative genetic studies of divergence between the apple and
      hawthorn-infesting host races.

PMID- 20035632
TI  - Hypoxia-inducible factor-1alpha gene polymorphisms and cancer risk: a meta
      analysis.
AB  - BACKGROUND: The results from the published studies on the association between
      hypoxia-inducible factor -1alpha (HIF-1alpha) polymorphisms and cancer risk are
      conflicting. In this meta-analysis, we aimed to investigate the association
      between HIF-1alpha 1772 C/T and 1790 G/A polymorphisms and cancer. METHODS: The
      meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387
      controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026
      controls. Allelic and genotypic comparisons between cases and controls were
      evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also
      performed. We included prostate cancer in male subgroup, and female specific
      cancers in female subgroup. RESULTS: For the 1772 C/T polymorphism, the analysis
      showed that the T allele and genotype TT were significantly associated with
      higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01,
      1.65)], P = 0.04, P(heterogeneity) < 0.00001, and OR = 2.18 [95% CI (1.32,
      3.62)], P = 0.003, P(heterogeneity) = 0.02, respectively. The effect of the
      genotype TT on cancer especially exists in Caucasians and female subjects: OR =
      2.40 [95% CI (1.26, 4.59)], P = 0.008, P(heterogeneity) = 0.02, and OR = 3.60
      [95% CI (1.17, 11.11)], P = 0.03, P(heterogeneity) = 0.02, respectively. For the
      1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and
      dominant model comparison suggested a significant association of 1790 G/A
      polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08,
      0.90)], P = 0.03, P(heterogeneity) = 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P
      = 0.04, P(heterogeneity) = 0.41, respectively. The frequency of the HIF-1alpha
      1790 A allele was very low and only two studies were included in the breast
      cancer subgroup. CONCLUSIONS: Our meta-analysis suggests that the HIF-1alpha 1772
      C/T polymorphism is significantly associated with higher cancer risk, and 1790
      G/A polymorphism is significantly associated with decreased breast cancer risk.
      The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians
      and female subjects. Only female specific cancers were included in female
      subgroup, which indicates that the 1772 C/T polymorphism is significantly
      associated with an increased risk for female specific cancers. The association
      between the 1790 G/A polymorphism and lower breast cancer risk could be due to
      chance.

PMID- 20035633
TI  - The Systemic Inflammatory Response Syndrome (SIRS) in acutely hospitalised
      medical patients: a cohort study.
AB  - BACKGROUND: Sepsis is an infection which has evoked a systemic inflammatory
      response. Clinically, the Systemic Inflammatory Response Syndrome (SIRS) is
      identified by two or more symptoms including fever or hypothermia, tachycardia,
      tachypnoea and change in blood leucocyte count. The relationship between SIRS
      symptoms and morbidity and mortality in medical emergency ward patients is
      unknown. METHODS: We conducted a prospective cohort study of the frequency of
      SIRS and its relationship to sepsis and death among acutely hospitalised medical
      patients. In 437 consecutive patients, SIRS status, blood pressure, infection and
      comorbidity on admission was registered together with 28-day mortality. RESULTS:
      A hundred and fifty-four patients (35%) had SIRS on admission, 211 patients (48%)
      had no SIRS, and 72 patients (16%) had insufficient data to evaluate their SIRS
      status. SIRS patients were 2.2 times more frequently infected, with 66/154 SIRS
      patients versus 41/211 non-SIRS patients: p < 0.001, relative risk (RR) 2.2 (95%
      confidence interval (CI) 1.6-3.1), and they had a 6.9 times higher 28-day
      mortality than non-SIRS patients with 15/154 SIRS patients versus 3/211 non-SIRS
      patients: p = 0.001, RR 6.9 (95% CI 2.0-23.3). Most of the deaths among patients
      with SIRS occurred among patients with malignant conditions. Septic shock
      developed in 4/154 (3%) of the patients with SIRS, whereas this occurred in only
      one of the 211 patients (0.5%) without SIRS on arrival: p = 0.08, RR 5.5 (95% CI
      0.6-48.6). CONCLUSION: We found SIRS status on admission to be moderately
      associated with infection and strongly related to 28-day mortality.

PMID- 20035634
TI  - Differential expression of apoptotic genes PDIA3 and MAP3K5 distinguishes between
      low- and high-risk prostate cancer.
AB  - BACKGROUND: Despite recent progress in the identification of genetic and
      molecular alterations in prostate cancer, markers associated with tumor
      progression are scarce. Therefore precise diagnosis of patients and prognosis of
      the disease remain difficult. This study investigated novel molecular markers
      discriminating between low and highly aggressive types of prostate cancer.
      RESULTS: Using 52 microdissected cell populations of low- and high-risk prostate
      tumors, we identified via global cDNA microarrays analysis almost 1200 genes
      being differentially expressed among these groups. These genes were analyzed by
      statistical, pathway and gene enrichment methods. Twenty selected candidate genes
      were verified by quantitative real time PCR and immunohistochemistry. In
      concordance with the mRNA levels, two genes MAP3K5 and PDIA3 exposed differential
      protein expression. Functional characterization of PDIA3 revealed a pro-apoptotic
      role of this gene in PC3 prostate cancer cells. CONCLUSIONS: Our analyses provide
      deeper insights into the molecular changes occurring during prostate cancer
      progression. The genes MAP3K5 and PDIA3 are associated with malignant stages of
      prostate cancer and therefore provide novel potential biomarkers.

PMID- 20035635
TI  - Effects of estrogens and bladder inflammation on mitogen-activated protein
      kinases in lumbosacral dorsal root ganglia from adult female rats.
AB  - BACKGROUND: Interstitial cystitis is a chronic condition associated with bladder
      inflammation and, like a number of other chronic pain states, symptoms associated
      with interstitial cystitis are more common in females and fluctuate during the
      menstrual cycle. The aim of this study was to determine if estrogens could
      directly modulate signalling pathways within bladder sensory neurons, such as
      extracellular signal-related kinase (ERK) and p38 mitogen-activated protein (MAP)
      kinases. These signalling pathways have been implicated in neuronal plasticity
      underlying development of inflammatory somatic pain but have not been as
      extensively investigated in visceral nociceptors. We have focused on lumbosacral
      dorsal root ganglion (DRG) neurons projecting to pelvic viscera (L1, L2, L6, S1)
      of adult female Sprague-Dawley rats and performed both in vitro and in vivo
      manipulations to compare the effects of short- and long-term changes in estrogen
      levels on MAPK expression and activation. We have also investigated if prolonged
      estrogen deprivation influences the effects of lower urinary tract inflammation
      on MAPK signalling. RESULTS: In studies of isolated DRG neurons in short-term
      (overnight) culture, we found that estradiol and estrogen receptor (ER) agonists
      rapidly stimulated ER-dependent p38 phosphorylation relative to total p38.
      Examination of DRGs following chronic estrogen deprivation in vivo (ovariectomy)
      showed a parallel increase in total and phosphorylated p38 (relative to beta
      tubulin). We also observed an increase in ERK1 phosphorylation (relative to total
      ERK1), but no change in ERK1 expression (relative to beta-tubulin). We observed
      no change in ERK2 expression or phosphorylation. Although ovariectomy increased
      the level of phosphorylated ERK1 (vs. total ERK1), cyclophosphamide-induced lower
      urinary tract inflammation did not cause a net increase of either ERK1 or ERK2,
      or their phosphorylation. Inflammation did, however, cause an increase in p38
      protein levels, relative to beta-tubulin. Prior ovariectomy did not alter the
      response to inflammation. CONCLUSIONS: These results provide new insights into
      the complex effects of estrogens on bladder nociceptor signalling. The diversity
      of estrogen actions in these ganglia raises the possibility of developing new
      ways to modulate their function in pelvic hyperactivity or pain states.

PMID- 20035637
TI  - Mitochondrial dysfunction and biogenesis in the pathogenesis of Parkinson's
      disease.
AB  - Parkinson's disease (PD) is a progressive neurological disorder marked by
      nigrostriatal dopaminergic degeneration and development of cytoplasmic aggregates
      known as Lewy bodies. The impact of this disease is indicated by the fact that
      mortality is two to five times as high among affected persons as among age
      matched controls. However, the cause of PD is still unknown and no cure is
      available at present. Several biochemical abnormalities have been described in
      the brains of patients with PD, including oxidative stress and mitochondrial
      dysfunction. Recent identification of specific gene mutations that cause PD has
      further reinforced the relevance of oxidative stress and mitochondrial
      dysfunction in the familial and sporadic forms of the disease. The proteins that
      are reported to be related to familial PD-PTEN-induced putative kinase 1 (PINK1),
      DJ-1, alpha- synuclein, leucine-rich repeat kinase 2 (LRRK2), and, possibly,
      parkin-are either mitochondrial proteins or are associated with mitochondria, and
      all are involved in pathways that elicit oxidative stress or free radical damage.
      Mitochondria are continually exposed to reactive oxygen species and accumulate
      oxidative damage more rapidly than the rest of the cell. Therefore, Parkinson's
      disease has been suggested to be associated with mitochondrial dysfunction. Since
      mitochondria are the major intracellular organelles that regulate both cell
      survival and death, clarifying the involvement of mitochondrial dysfunction and
      biogenesis during the process of PD could provide treatment strategies that might
      successfully intervene in the pathogenesis and slow the progression of the
      disease.

PMID- 20035636
TI  - Comparing three short questionnaires to detect psychosocial dysfunction among
      primary school children: a randomized method.
AB  - BACKGROUND: Good questionnaires are essential to support the early identification
      of children with psychosocial dysfunction in community based settings. Our aim
      was to assess which of three short questionnaires was most suitable for this
      identification among school-aged children METHODS: A community-based sample of
      2,066 parents of children aged 7-12 years (85% of those eligible) filled out the
      Child Behavior Checklist (CBCL) and - randomly determined - one of three
      questionnaires to be compared: the Strengths and Difficulties Questionnaire with
      Impact Supplement (SDQ), the Pediatric Symptom Checklist (PSC) and the PSYBOBA, a
      Dutch-origin questionnaire. Preventive Child Healthcare professionals assessed
      children's psychosocial functioning during routine health examinations. We
      assessed the scale structure (by means of Structural Equation Modelling),
      validity (correlation coefficients, sensitivity and specificity) and usability
      (ratings by parents and professionals) of each questionnaire and the degree to
      which they could improve the identification based only on clinical assessment
      (logistic regression). RESULTS: For the three questionnaires, Cronbach's alphas
      varied between 0.80 and 0.89. Sensitivities for a clinical CBCL at a cut off
      point with specificity = 0.90 varied between 0.78 and 0.86 for the three
      questionnaires. Areas under the Receiver Operating Curve, using the CBCL as
      criterion, varied between 0.93 and 0.96. No differences were statistically
      significant. All three questionnaires added information to the clinical
      assessment. Odds ratios (95% confidence intervals) for added information were
      PSC: 29.3 (14.4-59.8), SDQ: 55.0 (23.1-131.2) and PSYBOBA: 68.5 (28.3-165.6).
      Parents preferred the SDQ and PSYBOBA. Preventive Child Health Care professionals
      preferred the SDQ. CONCLUSIONS: This randomized comparison of three
      questionnaires shows that each of the three questionnaires can improve the
      detection of psychosocial dysfunction among children substantially.

PMID- 20035638
TI  - Variation and clinical significance of extensor pollicis brevis: a study in South
      Indian cadavers.
AB  - BACKGROUND: de Quervain's disease is a condition in which there is pain in the
      radial styloid process caused by stenosing tenosynovitis of the abductor pollicis
      longus (APL) or/and extensor pollicis brevis (EPB) tendons in the first extensor
      compartment of the wrist. In this study we studied variations in the tendons of
      the EPB in the first extensor compartment and its site of insertion. METHODS: One
      hundred fifty six upper limbs from adult cadavers of south Indian origin were
      dissected to observe the number of EPB tendons and the presence of an osseo
      fibrous septum in the first extensor compartment of the wrist. RESULTS: The EPB
      had a single tendon in 133 limbs, double tendons in 17 limbs and triple tendons
      in only 6 limbs. The EPB was present in all of the upper limbs in our study. In
      34.6% of cases, the tendons of the EPB were separated from the tendons of APL by
      an osseo-fibrous septum in the first extensor compartment. CONCLUSION: Variation
      in the number of EPB tendons and site of insertion should be taken into
      consideration by clinicians and surgeons when performing surgical decompression
      of the first extensor compartment of the wrist in de Quervain's syndrome.
      Surgical failure may occur due to overlooking variations in EPB tendons or
      septation of the first extensor compartment.

PMID- 20035639
TI  - Uric Acid is not an independent predictor of cardiovascular death in patients
      with angiographically proven coronary artery disease.
AB  - BACKGROUND: The aim of this study is to investigate the impact of uric acid on
      clinical outcomes in patients with angiographically proven coronary artery
      disease. METHOD: Six hundred and forty seven consecutive patients with
      angiographically proven significant coronary artery disease were enrolled in this
      retrospective study. Patients were assigned to serum uric acid level >or= 6.4
      mg/dL and < 6.4 mg/dL groups based on baseline fasting uric acid levels and
      determined by a receiver operating characteristic curve. The mean follow-up
      duration was 4.6 +/- 1.1 years after coronary angiography. The primary endpoints
      were all cause mortality and death from cardiovascular disease. RESULTS: The five
      year survival rates for patients free from all-cause mortality with levels of
      uric acid >or= 6.4 mg/dL and < 6.4 mg/dL were 82% and 92% respectively (p <
      0.0001). Five-year survival rates for patients free from cardiovascular mortality
      with levels of uric acid uric acid >or= 6.4 mg/dL and < 6.4 mg/dL were 91% and
      97% respectively (p = 0.003). Multivariate Cox regression analysis showed that
      serum uric acid was an independent predictor of all-cause death (p = 0.01) but
      was not an independent predictor of cardiovascular mortality (p = 0.063) after
      adjusting for multi-vessel coronary artery disease, chronic renal insufficiency
      and a left ventricular ejection fraction < 40%. CONCLUSIONS: After multivariate
      adjustment, the fasting serum uric acid level was an independent predictor of all
      cause mortality, but probably not an independent predictor of cardiovascular
      mortality in patients with angiographically proven coronary artery disease.

PMID- 20035640
TI  - FibroQ: an easy and useful noninvasive test for predicting liver fibrosis in
      patients with chronic viral hepatitis.
AB  - BACKGROUND: Liver biopsy-the gold standard in assessing liver histology-is
      recommended before all antiviral treatment. However, this procedure may cause
      complications, is costly, and is limited by sampling errors. Hence, noninvasive
      tests have been proposed to assess the severity of hepatic fibrosis. We propose a
      novel noninvasive index for predicting liver fibrosis, named fibro-quotient
      (FibroQ), and compared the diagnostic accuracies of FibroQ, aspartate
      aminotransferase (AST)-to-platelet ratio index (APRI), and AST/alanine
      aminotransferase (ALT) ratio (AAR). METHODS: This retrospective cohort study
      included 140 consecutive patients with chronic viral hepatitis who had undergone
      percutaneous liver biopsy before treatment at the Chang Gung Memorial Hospital,
      Chiayi from May 2005 through December 2007. The clinical data including sex, age,
      AST, ALT, platelet count, prothrombin time (PT) international normalized ratio
      (INR), and the Metavir fibrosis score (F0 to F4) of liver histology were
      recorded. APRI, AAR, and FibroQ were calculated. Receiver operating
      characteristic (ROC) curves were constructed to compare the accuracies of these
      three noninvasive tests in predicting significant fibrosis in patients with
      chronic viral hepatitis. RESULTS: FibroQ performed better than APRI, but was
      equal to AAR, in the prediction of significant fibrosis [area under the receiver
      operating characteristic curve (AUC): 0.783 vs 0.631 (p = 0.02) and 0.783 vs
      0.733 (p = 0.26), respectively] and cirrhosis (AUC: 0.791 vs 0.634 (p = 0.03),
      and 0.791 vs 0.782 (p= 0.47), respectively). Using FibroQ below the lower cutoff
      value (0.6) and above the higher cutoff value (1.6), 108 of 140 (77.1%) patients
      could be identified correctly to have or not have significant fibrosis.
      CONCLUSION: FibroQ, a novel noninvasive test, is an useful and easy tool to
      evaluate liver fibrosis in patients with chronic viral hepatitis and has better
      accuracy than APRI and is equal to AAR. Further prospective studies are warranted
      to validate its efficacy.

PMID- 20035641
TI  - Risk factors associated with transrectal ultrasound guided prostate needle biopsy
      in patients with prostate cancer.
AB  - BACKGROUND: Transrectal ultrasound (TRUS) guided prostate needle biopsy is a
      commonly used diagnostic procedure. We determined associated risk factors for
      patients who suffered major complications and required hospitalization after TRUS
      guided prostate biopsy. METHODS: A total of 1,529 patients, 27 to 92 years old
      (mean 67.6 years) were included in this study conducted between January 2003 and
      July 2006. Each patient underwent sextant prostate biopsy under transrectal
      ultrasound guidance. Six-core transrectal biopsies were performed by urologists,
      consultant urologists and residents in training. RESULTS: The mean prostate
      specific antigen (PSA) level and prostate volume were 113.2 ng/ml and 46.2 grams,
      respectively. One hundred forty-seven patients had complications. Some patients
      may have had more than one complication, but no major sequelae were seen
      immediately after biopsy. Sixty-two (4.1%) of these patients had gross hematuria,
      while 26 (1.7%) had acute urinary retention, 21 (1.4%) had urinary tract
      infection, 17 (1.1%) had hematospermia,14 (0.9%) had anal bleeding and 7 (0.5%)
      had anal pain. Urinary tract infection and rectal preparation were found
      significantly associated with complications. CONCLUSIONS: The results of our
      study demonstrate that minor complications occur without sequelae. Thus, TRUS
      guided prostate needle biopsy is a safe and effective diagnostic tool. Urinary
      tract infection and rectal preparation might affect the complication rate.

PMID- 20035642
TI  - Follow-up of developmental profiles in children with spastic quadriplegic
      cerebral palsy.
AB  - BACKGROUND: The aim of this study was to investigate longitudinal changes in the
      developmental profiles of children with spastic quadriplegic (SQ) cerebral palsy
      (CP). Additionally, the relationship of developmental functions between the
      initial and final stages was determined. METHODS: This prospective study enrolled
      forty-six children with SQ CP between 2-6 years old and assessed their
      developmental profiles using the Chinese Child Developmental Inventory on the
      initial and final assessments. The interval between two assessments was 1.0 +/-
      0.3 years. Eight developmental domains, including gross motor, fine motor,
      expressive language, concept comprehension, situation comprehension, self help,
      personal social and general development, were evaluated and qualified by the
      development quotient (DQ). The DQ change index (%) was calculated to evaluate the
      differences in each domain between the two assessments. The paired t test was
      used to compare differences in each domain between the two assessments. Pearson's
      correlation was used to analyze the relationship of each domain between the final
      and initial assessments. RESULTS: Children with SQ CP had lower DQs than normal
      children in all developmental functions on both assessments (23 - 66%). The DQ
      distributions were lowest in the gross motor and self help domains, higher in the
      fine motor, situation comprehension, and personal social domains, and highest in
      the expressive language, concept comprehension, and general development domains.
      Except for the fine motor and concept comprehension domains, the DQs of the
      developmental functions were significantly decreased on the final assessment (p <
      0.05). CONCLUSION: These findings suggest preschool children with SQ CP had
      impairments in the full spectrum of developmental profiles. The course of
      developmental profiles evolves with age. Most developmental functions did not
      increase proportionally with increasing age in children with SQ CP.

PMID- 20035643
TI  - Comprehensive dental treatment under general anesthesia in healthy and disabled
      children.
AB  - BACKGROUND: Differences in dental treatment under general anesthesia (GA) in
      healthy and disabled children are rarely reported. This retrospective study
      evaluated the characteristics and treatment modalities performed under general
      anesthesia in pediatric dental patients at Taipei Chang Gung Memorial Hospital
      between 2004 and 2005, and compared the different treatment patterns performed in
      healthy children and children with special health care needs. METHODS: The data
      were reviewed in pediatric patients from 1 to 18 years old who underwent dental
      treatment performed under general anesthesia from January 2004 to December 2005.
      Patients with special health care needs who had at least one type of mental or
      physical disability were assigned to the disabled group (Group D) and the other
      healthy patients were assigned to the healthy group (Group H). The treatment
      modalities of operative restoration, crowns, pulp therapy, sealant and extracted
      teeth were compared in the two groups. RESULTS: A total of 185 patients were
      assigned to group H and 112 to group D. The patients in group D were
      significantly older than those in group H. There were no significant differences
      in the mean number of teeth treated between the two groups. However, there was a
      significantly greater mean total number of teeth extracted in group D patients (p
      < 0.001). In addition, there were more stainless steel crown reconstructions (p <
      0.05) and pulp therapies (p < 0.001) performed in group H patients. In group D,
      there were no significant differences in the total number of teeth extracted
      between the 1-3 year old patients and the 3-6 year-old patients (p = 0.99).
      CONCLUSIONS: For very young children or those with special health care needs,
      dental treatment performed under general anesthesia is beneficial and efficient.
      The findings of this study suggest that underlying medical or mental conditions
      may influence the dental condition and treatment modality provided.

PMID- 20035644
TI  - Effect of warm lidocaine on the sensory onset of epidural anesthesia: a
      randomized trial.
AB  - BACKGROUND: Administration of local anesthetics at body temperature has been
      reported to shorten the onset time of regional block; however, studies examining
      the effects of warmed lidocaine on the onset of epidural anesthesia are limited.
      Here, we ascertain whether warming lidocaine solution to body temperature
      shortens the time to onset of epidural anesthesia. METHODS: Eighty patients were
      randomly allocated into two groups of equal size. Both received 16 ml of
      lidocaine solution injected via the epidural route at the L4- 5 interspace, with
      one group receiving the solution at room temperature (RT, 18 degrees Celsius) and
      the other receiving the solution warmed to body temperature (BT, 36 degrees
      Celsius). Sensory blocks at the T10, T12, and L3 dermatomes, perianal region, and
      upper level dermatomes were assessed by pinprick and their onset times recorded.
      Patients with incomplete anal sensory block were excluded. RESULTS: Seventy-seven
      patients were included for analysis. The pH value of the local anesthetic
      solution was significantly increased at BT compared to RT (6.57 +/- 0.11 vs. 6.47
      +/- 0.11, p < 0.05). Significantly shorter onset times of sensory block were
      observed at the T12 (10.03 +/- 3.55 vs. 11.71 +/- 3.76 min) and L3 (7.49 +/- 3.19
      vs. 9.92 +/- 3.46 min) dermatomes for the BT compared to the RT group (p <
      0.005). The onset time of sensory block at the anal region was also shorter in
      the BT than the RT group (11.54 +/- 4.35 vs. 12.50 +/- 4.06 min, p < 0.05). No
      differences between groups with respect to gender, age, height, weight, visual
      analogue pain score, upper sensory level, or adverse events were observed.
      CONCLUSIONS: Administration of lidocaine at BT compared to RT shortens the onset
      time of sensory block in epidural anesthesia with no associated adverse effects.

PMID- 20035645
TI  - Health promoting lifestyles and related factors in pregnant women.
AB  - BACKGROUND: The purpose of this study was to explore health promoting lifestyles
      and related factors in pregnant women. METHODS: This was a descriptive study
      using convenience sampling. Altogether, 172 pregnant women were recruited from a
      medical center in southern Taiwan. Personal data was collected, and the
      instruments used included perceived health status, self-efficacy of health
      behaviors, perception of family or peers' health-promoting behaviors, and Health
      Promoting Lifestyle Profile (HPLP Pi). RESULTS: The results showed that the
      standardized total score of health promoting lifestyles was 66.88 (moderate
      level). The subscales of the HPLP Pi in descending order of standardized scores
      were as follows: "interpersonal relationships," "health responsibility,"
      "psychological wellness," "nutrition," "stress management" and "physical
      activity." There were significant differences in the total scores of the HPLP Pi
      among subjects with different educational level, socioeconomic status, chronic
      diseases, exercise habits, length of sleep, and perceived health status. Both
      perception of health-promoting behaviors among family (or peers) and self
      efficacy of health behaviors had significantly positive relationships with health
      promoting lifestyles. Perception of the family or peers' health-promoting
      behaviors, self-efficacy of health behaviors, perceived health status and chronic
      diseases were the four significant predictors of health-promoting lifestyles,
      accounting for 62.4% of the variance. CONCLUSION: The findings of this study
      could be used as a reference for prenatal care, nursing education, and maternal /
      neonatal health policies.

PMID- 20035646
TI  - Idiopathic spinal epidural lipomatosis - two cases report and review of
      literature.
AB  - Spinal epidural lipomatosis (SEL), an abnormal localized or tumor-like
      accumulation of fat in the epidural space, is an infrequent complication of
      chronic steroid usage and an uncommon cause of spinal cord compression. During
      the period of 1990 to 2006, we have two cases of medically heath SEL patients
      without history of steroid administration. Their initial clinical manifestations
      were low back pain, progressive lower extremities weakness, numbness, followed by
      rapid deterioration of neurogenic intermittent claudication. They were
      misdiagnosed and treated as degenerative spinal disease for a long time. Due to
      prominent neurological deficit, lumbar magnetic resonance image (MRI) was
      obtained and showed SEL. These 2 patients all underwent laminectomy and removal
      of epidural fat. Postoperatively, they both showed improvement. We reviewed the
      literature and discussed the current concept in the management of SEL.

PMID- 20035647
TI  - Alternative therapy for autosensitization dermatitis.
AB  - During outdoor activities, Dendrocnide meyeniana can induce severe acute
      dermatitis, which usually needs topical or systemic corticosteroids, and oral
      antihistamine to alleviate associated symptoms such as exudation, pruritus or
      burning sensation. In this paper we report a 14-year-old male, with
      autosensitization dermatitis caused by Dendrocnide meyeniana, who had
      erythematous papules accompanied by itching and stinging sensations over left
      inner elbow first and then extended to the trunk and limbs. Based on the theory
      of traditional Chinese medicine (TCM) and pharmacological studies, the combined
      formula of Xiao-feng-san (XFS) and Huang-lian-jie-du-tang (HLJDT) was prescribed
      in the form of concentrated herbal extracts per oral. Remission of skin lesions
      and the accompanied symptoms was observed after treatment using the TCM formula
      for 7 days. Follow-up of the patient showed no relapse. We therefore conclude
      that TCM herbs may provide an alternative treatment for autosensitization
      dermatitis caused by Dendrocnide meyeniana.

PMID- 20035648
TI  - Midline laser glossectomy: complications and risks are against the potential
      benefits.

PMID- 20035669
TI  - [Monoclonal antibodies: fantastic tools still blooming].

PMID- 20035670
TI  - [From the ancient serotherapy to naked antibodies: a century of successful
      targeted therapies].
AB  - Monoclonal antibodies and molecular engineering have renewed the ancient
      serotherapy, multiplying the possibilities of therapeutic interventions and
      providing many new clinical successes! Standing back about this history allows us
      to better understand the evolution of concepts underlying the therapeutic use of
      antibodies, as well as the maturation of the tool itself. The different
      principles of therapeutic targeting will be successively tackled, from their
      sometimes hundred year-old conception until the most recent clinical
      developments: antibodies neutralizing toxins and soluble antigens, anti-microbial
      antibodies, cytotoxic antibodies, tumour-specific antibodies, cell function 
      modifying antibodies, etc. This overview will finally offer the opportunity to
      introduce a new pharmacological classification of the entire class of
      unconjugated -therapeutic antibodies.

PMID- 20035671
TI  - [A successful story of fused cells: monoclonal antibodies].

PMID- 20035672
TI  - [Antibodies: better knowledge for a better use].
AB  - The therapeutic use of monoclonal antibodies is growing exponentially. Our
      knowledge on antibody structure, in particular that of IgG1, largely used in the
      clinic, has progressed remarkably. However, some formidable challenges still
      remain to be confronted, among which the increase of a yet-limited antibody
      efficacy, the lowering of the frequency of serious clinical adverse events, and
      the establishment of pre-clinical models that can be reliably extrapolated to
      humans represent major goals. The selection of relevant target antigens with
      regard to the pathology to be treated and to the expected effects of the antibody
      used is also a critical parameter. Facing these challenges, the amazing molecular
      plasticity of antibodies, as well as new antibody engineering approaches based on
      the most recent insights on the structure and biology of antibodies and their
      targets represent areas of research that will make monoclonal antibodies
      remarkable drugs for human health in a near future.

PMID- 20035673
TI  - [Antibody databases: IMGT, a French platform of world-wide interest].
AB  - IMGT, the international ImMunoGeneTics information system, was created in 1989 in
      Montpellier by the Laboratoire d'ImmunoGenetique Moleculaire (LIGM) headed by the
      Professors Marie-Paule and Gerard Lefranc (University Montpellier 2 and CNRS).
      IMGT is specialized in the sequences, structures and genetic data of the
      immunoglobulins (IG) or antibodies, T cell receptors (TR), major
      histocompatibilite complex (MHC), proteins of the IgSF and MhcSF superfamilies,
      and related proteins of the immune system. The data analysis and the
      standardization of the annotation are based on IMGT-ONTOLOGY, the first ontology
      in the domain. IMGT is to-day the international reference system in
      immunogenetics and immunoinformatics, used in fundamental, medical and
      biotechnological research and, in particular, in antibody -engineering and
      humanization.

PMID- 20035674
TI  - [Therapeutic antibodies and related products: choosing the right structure for
      success].
AB  - Monoclonal antibodies (mAb) and related-products represent the fastest growing
      class of therapeutics in the biotechnological and pharmaceutical industry. In
      just as short as 20 years, more than 30 immunoglobulins (IgG) and derivatives
      have been approved in a wide range of indications (oncology, inflammation and
      auto-immunity, transplantation, angioplasty, hematology, ophthalmology, viral
      infections, allergy). The mAb structure toolbox contains mouse, chimeric,
      humanized and human antibodies from different isotypes (IgG1, 2 and 4), as well
      as IgG-related products (immunoconjugates, radio-immunoconjugates, Fab fragments,
      Fc-fusion proteins and peptides, bispecifics). Furthermore from a structural
      point of view, mAb glycosylation is linked to their production systems and may
      impact on their effector functions and immunogenicity. Based on the current
      knowledge, choosing the right antibody format, isotype and glycosylation profile
      are some of the key issues to address early during the lead selection.

PMID- 20035675
TI  - [Recombinant proteins or monoclonal antibodies: comparative properties and
      interest in rheumatoid arthritis].
AB  - Therapeutics options for inflammatory diseases, such as rheumatoid arthritis
      (RA), have increased tremendously in the past decade with the introduction of
      biologic therapies, such as monoclonal antibodies or recombinant fusion proteins.
      These have proven to be highly successful in treating inflammatory or autoimmune
      diseases, by blocking certain key molecules involved in the pathogenesis of the
      illness, cytokines (TNF) or immune coactivators (CTLA-4). Thus in rheumatoid
      arthritis, TNF can be neutralized both by monoclonal antibodies (adalimumab,
      infliximab) or recombinant inhibitors such as etanercept or CTLA-4 Ig abatacept.
      All have been marketed and proven to be highly effective in the treatment of RA,
      and we will discuss parameters which are taken into account to select monoclonal
      antibody or recombinant inhibitors. These include drug-related (target affinity,
      pharmacokinetics, mechanisms of action, etc.) and patient - (efficacy and side
      effects) or disease-related characteristics. Their impact on current clinical
      practice and future trends are discussed.

PMID- 20035676
TI  - [Radiolabeled antibodies for cancer treatment].
AB  - The first treatment ever by radio-immunotherapy (RIT) was performed by William H.
      Beierwaltes in 1951 and was a success. Fifty years later, the main question is to
      find ways of extending the success of radiolabelled anti-CD20 antibodies in
      indolent non-Hodgkin's lymphoma to other forms of cancer. Solid tumours are much
      more radioresistant than lymphomas, but they respond to RIT if the lesions are
      small. Clinical situations of residual or minimal disease are thus the most
      likely to benefit from RIT in the adjuvant or consolidation settings. For
      disseminated disease, like leukemias or myelomas, the problem is different: beta-
      particles emitted by the radioactive atoms classically used for cancer treatment
      (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to
      1 cm) and are not very effective against isolated cells. Advances in RIT progress
      in two directions. One is the development of pretargeting strategies in which the
      antibody is not labelled but used to provide binding sites to small molecular
      weight radioactivity vectors (biotin, haptens). These techniques have been shown
      to increase tumour to non-target uptake ratios and anti-tumour efficacy has been
      demonstrated in the clinic. The other approach is the use of radionuclides
      adapted to the various clinical situations. Lutetium-177 or copper-67, because of
      the lower energy of their emission, their relatively long half-life and good
      gamma emission, may significantly improve RIT efficacy and acceptability. Beyond
      that, radionuclides emitting particles such as alpha particles or Auger
      electrons, much more efficient to kill isolated tumour cells, are being tested
      for RIT in the clinic. Finally, RIT should be integrated with other cancer
      treatment approaches in multimodality protocols. Thus RIT, now a mature
      technology, should enter a phase of well designed and focused clinical
      developments that may be expected to afford significant therapeutic advances.

PMID- 20035677
TI  - [Immunoconjugates, drug-armed antibodies to fight against cancer].
AB  - Monoclonal antibodies constitute a growing class of therapeutic agents. They are
      classically used in combination with chemotherapeutic drugs for cancer treatment.
      The concept of coupling a cytotoxic agent to an antibody can be viewed as a means
      to confer a selectivity for tumoral cells to highly cytotoxic drugs which cannot
      be used in human, or a higher power to antibodies which have a low anti-tumoral
      activity on their own. Gemtuzumab ozogamicin is the only drug-armed antibody
      available on the market, for the treatment of acute myeloid leukaemia. Other
      immunoconjugates are currently under clinical development. The most used
      cytotoxic agents derive from calicheamicin, maytansin and auristatin, compounds
      which are 100 to 1 000 fold more toxic than the classical chemotherapeutic drugs.
      Today, we know that the efficacy of an immunoconjugate depends not only on the
      coupled cytotoxic agent, but also on the selected target, the coupling method and
      the linker.

PMID- 20035678
TI  - [Neonatal Fc receptor, key control of immunoglobulins biodistribution].
AB  - In 1969, Brambell, while studying the long serum half-life of IgG and their
      ability to cross the materno-foetal barrier, attributed these two properties to
      the existence of a specific Fc receptor, which was later denominated FcRn for
      neonatal Fc receptor. The resolution of its structure revealed that it is a MHC
      class-I-like molecule. FcRn is able to load IgG and albumin in a pH-dependent
      manner. It acts as an intracellular transport protein and as such is controling
      the serum half-life of these proteins (apical recycling of IgG and albumin in
      endothelial cells), IgG biodistribution (apical to basolateral and basolateral to
      apical transport of IgG in epithelial and endothelial cells) and it may also
      contribute to phagocytosis. FcRn is thus a key partner in the pharmacokinetics of
      therapeutic antibodies, opening interesting prospects for optimisation of their
      use.

PMID- 20035679
TI  - [Pharmacokinetics (PK) of mAbs].
AB  - The human Fc portion of humanized monoclonal antibodies (mAb) gives them a half
      life of around 21 days, similar to that of endogenous immunoglobulin G (IgG).
      Neonatal Fc receptor (FcRn) plays a major role in the pharmacokinetics (PK) of
      mAbs. By protecting them from degradation, it is responsible for their long half
      life and by allowing their transcytosis, it influences their absorption and their
      distribution. After subcutaneous administration, the absorption of mAbs is slow
      and incomplete. Most of them are still administered intravenously. Their
      distribution in tissues is poorly known. It seems limited and certain organs,
      such as the central nervous system, may be protected by FcRn. The elimination of
      mAbs is partly mediated by binding to their target-antigen, a mechanism that
      leads to dose-dependent PK. The interindividual variability in mAb PK is
      clinically relevant and its main known origins are demographic factors, antigen
      mass and immunization. Complex PK models are needed to describe satisfactorily
      their fate in the body and their concentration-effect relationship.

PMID- 20035680
TI  - [Therapeutic antibodies: importance of galenics for efficacy and safety].
AB  - Monoclonal antibodies and their derivatives such as antibody fragments,
      immunoconjugates and Fc fusions, represent the majority of therapeutic proteins
      in clinical development. Recent successes of such molecules in cancer and in the
      treatment of autoimmune diseases found a great hope in biotherapeutics. The
      progress in genetic engineering and in analytical development allowed the
      production of increasingly humanized antibodies, and thus less immunogenic.
      However the use of such molecules in therapeutics would not be possible without a
      good comprehension of their degradation pathways and therefore the development of
      formulations and manufacturing processes ensuring them a good stability along
      their production, shipment, storage and administration. The present review
      summarizes the key degradation pathways of monoclonal antibodies and the
      formulation approaches allowing a satisfactory shelf-life, ensuring both
      efficiency and safety of such biomedicines.

PMID- 20035681
TI  - [Immunogenicity of therapeutic antibodies].
AB  - Unwanted immunogenicity, i.e., the developpement by patients of anti-drug
      antibodies is a significant problem with biologicals therapeutic reagents and can
      compromise clinical response. Over 20 antibodies currently on the market and over
      100 drug candidates are currently in clinical trials; all therapeutic antibodies
      are showing some level of immunogenicity, and although it has been reduced with
      the advent of antibodies including human sequences, or even humanised antibodies,
      this concern will not be totally eradicated. Whereas the actual anti-drug
      response can only be addressed during clinical development or post-marketing, the
      industry and the regulatory instances are facing a challenge to develop accurate
      procedures for the assessment of immunogenicity related to antibody therapeutics,
      addressing both the likelihood and the severity of the drug-related
      immunogenicity. This review will discuss the multiple factors that can contribute
      to a potential immunogenicity of protein therapeutics patient/disease related, as
      well as related to the drug itself, and the strategies to identify anti-drug
      antibodies, both in clinical and non clinical assays.

PMID- 20035682
TI  - [Producing several hundred of kilograms of monoclonal antibodies for therapy: a
      constant challenge].
AB  - Discovering and designing novel therapeutic monoclonal antibodies (mAb) is just
      the beginning. In order to support clinical evaluations and to reach the market
      place, rapid and cost effective production platforms are needed. Process
      development and production efficiency play a crucial role in this space since
      they influence the cost of good and ultimately wide access to these life-saving
      medications. Due to their therapeutic dosages and repeated uses, the yearly need
      for certain mAb, especially those used in the treatments of cancer and
      inflammation, amounts to several hundred of kilograms. Consequently, significant
      technological investments are needed to support these extraordinary large needs
      for such complex proteins, and the industry is constantly aiming at reducing
      production costs while maintaining product quality to high levels. This review
      discusses some of the critical scientific and engineering decisions, which span
      from the selection of cell-line expression platforms to choices of technologies,
      which influence mAbs cost of goods that need to be made along the development
      path of a therapeutic mAb.

PMID- 20035683
TI  - [Therapeutic monoclonal antibodies in onco-hematology].
AB  - Rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical
      practice in 1997, and has proven to be highly effective in the treatment of B
      lymphoproliferative disorders and autoimmune diseases. Despite such success, in
      vivo mechanisms of action of anti-CD20 have only recently began to be unraveled,
      pointing to the crucial role of antibody-dependent cellular cytotoxicity response
      mediated through Fcg receptor signalling. Better understanding of
      pharmacokinetics and factors influencing individual exposure mediated through
      anti-CD20 will allow to engineer these molecules to increase their effector
      responses. Meanwhile, other formats have also been investigated, such as
      radiolabeled anti-CD20, or coupling of antibodies to cytotoxic drugs such as anti
      CD33 used in myeloid leukemia. However these antibodies are used in combination
      with standard chemotherapy and cannot substitute for cytotoxic drugs. This review
      summarizes the knowledge acquired through our clinical use of anti-CD20 and
      authorized monoclonal antibodies in oncohematology and proposes some news areas
      that will lead to the development of new and more effective therapeutic
      strategies.

PMID- 20035684
TI  - [The potential of monoclonal antibodies in cancer : established trastuzumab and
      cetuximab and promising targets IGF-1R and c-MET].
AB  - Recent biotechnological advances allowed the development of a novel class of anti
      cancer drugs called monoclonal antibodies (mAb). To illustrate the potential of
      these new agents, two mAbs used in daily practice (i.e., trastuzumab and
      cetuximab) and two promising targets (i.e., IGF-1R and c-Met) for which mAbs
      should be available in a near future are discussed here. Trastuzumab and
      cetuximab deeply changed treatment strategies for breast, colon, and head and
      neck cancers. However their efficacy is observed in a fraction of patients only
      and is often time limited. Thus, current challenges are to better understand the
      mechanisms of action of mAbs, to identify mechanisms of resistance, to exploit
      the synergy between mAbs and chemotherapy drugs, and to better select patients
      with a potential benefit. Resolving these issues should pave the way for tailored
      treatment according to tumor and patient characteristics.

PMID- 20035685
TI  - [Tumour angiogenesis inhibition by therapeutic monoclonal antibodies].
AB  - The development of therapeutic monoclonal antibodies (mAb) provided many great
      advances in the treatment of some diseases, in particular cancers. In the
      treatment of cancers, tumour angiogenesis inhibition by mAb occupies a major
      place. Tumour angiogenesis is a highly complex multifactor process in which many
      molecules, which originate both in the tumor cells or their environment, display
      pro- or anti-angiogenic functions. Many molecular pathways, among which those
      triggered by vascular endothelial growth factor, platelet-derived growth factor
      and integrins, are currently under investigation in therapeutic anti-angiogenesis
      research. Bevacizumab is to date the only mAb targeting the tumour vasculature
      that is currently used in clinical practice. Clinical trials have revealed its
      efficacy in colorectal, breast, kidney and lung cancers and gliobastoma
      multiforme. Such a success confirms the effectiveness in the treatment of cancer
      of using mAb inhibiting tumour angiogenesis, and many mAb targeting different
      angiogenesis pathways will probably be developed. Beyond clinical oncology,
      angiogenesis inhibition by mAb is of increasing interest in many other fields of
      medicine. It could offer interesting therapeutic strategies in some
      cardiovascular or rheumatologic diseases and currently represents the standard
      cure in some blinding ocular disorders.

PMID- 20035686
TI  - [Monoclonal antibodies targeting VEGF in ophthalmology: the case of exudative age
      related macular degeneration].
AB  - Age-related macular degeneration (AMD) is the main cause of vision loss in the
      elderly in developed countries. The exudative AMD is the most frequent and severe
      form of the disease, leading to a rapid loss of vision. The results of MARINA and
      ANCHOR studies, two multicentric clinical trials analyzing the efficacy of anti
      VEGF in exudative AMD, have showed that this modality of treatment results in a
      stabilisation of the visual acuity in most cases (70%), and in visual improvement
      in 30 % of the cases. Up till now, the anti-VEGF approach represents a major step
      in the therapeutic strategy of this disease.

PMID- 20035687
TI  - [Monoclonal antibodies in chronic autoimmune inflammatory diseases].
AB  - Among chronic inflammatory diseases, rheumatoid arthritis is a common
      inflammatory and destructive arthropathy, characterized by the release of potent
      proinflammatory cytokines mostly TNFa and IL-1, which both mediate systemic
      effects and contribute to joint destruction. Many therapeutic agents have been
      proposed to antagonise these cytokines, among which monoclonal antibodies. Thus
      twenty years ago the anti-TNFa infliximab was the first monoclonal antibody to be
      proposed in a non-cancerous indication, rheumatoid arthritis. Since then, several
      other monoclonal antibodies and/or antagonists either targeting cytokines (IL-1,
      IL-6, RANKL), but also immune cellular effectors T and B cells, have been
      evaluated not only in rheumatoid arthritis, but also in systemic lupus, Crohn's
      disease, multiple sclerosis, or ankylosing spondylitis. Clinical benefit has been
      unambiguously demonstrated, but before these novel molecules enter routine
      clinical practice, several parameters will have to be accurately documented such
      as their safety, long term efficacy, and economical cost.

PMID- 20035688
TI  - [Monoclonal antibodies in multiple sclerosis].
AB  - Multiple sclerosis is the main source of significant disability in young adults
      and is associated with inflammation, demyelinisation and neurodegeneration.
      Several trials in the past ten years have tested b interfons and other
      immunomodulators, with some success. Recently, Natalizumab (Tysabri), a
      monoclonal antibody which targets the a4-integrin expressed by immune effectors,
      thus preventing their migration from the circulation into the brain tissue, has
      demonstrated previously unseen efficacy in preventing relapses and disease
      progression in patients with remitting multiple sclerosis. However, this
      enthusiasm has been tempered by observed cases of opportunistic infection and
      especially progressive multifocal leucoencephalopathy, which led to its
      restricted use to a precise subgroup of patients. This example underlines the
      difficult evaluation of the benefit/risk ratio experienced by the pratician with
      these new and often very efficient innovative therapeutics.

PMID- 20035689
TI  - [Monoclonal antibodies for treating infectious diseases].
AB  - Monoclonal antibodies (mAb) are attractive biologic drugs because of their
      specificity and well understood mechanisms of action. So far, most mAb have been
      developed for treating cancers or immunological disorders. However, the
      antibiotic resistance crisis, emerging viral diseases and bioterrorism have
      increased the development of anti-infectious mAb, for which more than twenty
      clinical trials are in progress to evaluate their safety and efficacy. The
      synergies obtained using combinations of anti-infectious mAb and small molecule
      drugs will certainly offer new opportunities for the treatment of infectious
      diseases.

PMID- 20035690
TI  - [Monoclonal antibodies in organ transplantation].
AB  - Polyclonal anti-lymphoyctes antibodies were first successfully used in the 1970
      in organ transplantation, but ten years later, monoclonal antibodies (mAb)
      emerged as a new class of immunosuppressive agents in transplantation with the
      potential to target highly specifically immune cells responsible for acute
      rejection. Some have proved their efficacy, such as mAb recognizing CD3- and CD25
      positive T cells and have been extensively studied in clinical trials. Others
      such as mAb against CD52 and CD20, are still under investigation; finally, the
      next challenge is, based on our improved understanding of the mechanisms of
      immune recognition and allograft rejection, to use these mAb either alone or in
      combination with standard immunosuppressive regimens to manipulate the allogenic
      response to reach antigen-specific tolerance desired in solid-organ
      transplantation.

PMID- 20035691
TI  - [Eculizumab in paroxysmal nocturnal hemoglobinuria].
AB  - Paroxysmal nocturnal hemoglobinuria is a rare acquired clonal of the
      hematopoietic stem cell due to acquired mutation of the PIG-A gene. This results
      in the lack of two GPI-anchored membrane proteins involved in the inhibition of
      complement attack, thus explaining red cells hemolysis. The development of an
      anti-C5 monoclonal antibody (eculizumab) had profoundly modified the treatment of
      the the hemolytic form of the disease.

PMID- 20035692
TI  - [Toxic effects and use of therapeutic monoclonal antibodies].
AB  - The extensive use of therapeutic monoclonal antibodies in clinic has shown that
      toxic effects may occur in patients. Examples such as muromonab (anti-CD3) and
      recently TGN1412 (anti-CD28) clearly establish that prediction of toxic effects
      for these targeted therapies is still complex. These undesirable effects can be
      classified in four categories: cytokine release syndrome, auto-immune diseases,
      organ toxicity and opportunistic infections. Immunogenicity, which is highly
      variable depending on the degree of humanization, could also potentially lead to
      adverse effects due to immune-complexes formation. The recent accident observed
      with the anti-CD28 TGN1412 has led to the conclusion that the relative confidence
      in the safety of monoclonal antibodies should be revised. In addition, the
      prediction of non-clinical models is rather limited and extrapolation of animal
      results to the human situation should be performed with caution. A better
      knowledge of the cellular target of the antibodies and of their mechanisms of
      action and the identification of risk factors (immune cell activation, wide
      expression of the target...) should improve the clinical safety of these
      products. .

PMID- 20035693
TI  - [Therapeutic monoclonal antibodies: update on the risk of opportunistic
      infections].
AB  - The large experience accumulated with the therapeutic use of monoclonal
      antibodies has revealed undesirable effects, among which opportunistic infections
      when prescribed in inflammatory or hematological diseases. This deleterious
      effect is a direct consequence of the immunosuppression induced by these
      antibodies through the blockade of several key pathways involved in both innate
      and adaptative immune responses, including migration of effector cells, depletion
      of B or T lymphocytes, inhibition of key cell-cell interactions. Four antibodies
      are concerned, targeting CD52, CD20, TNF-a and VLA-4, and major risks include
      activation of latent tuberculosis, or of normally silent viruses. Precise
      evaluation of these risks and understanding of their mechanisms have now led to
      the improvement of clinical safety, based on the detection of patients at risk,
      weighting of the benefit/risk ratio, and a very rigorous detection of latent
      infections before the onset of treatment by monoclonal antibodies know to induce
      immunosuppression.

PMID- 20035694
TI  - [EMABling antibodies: from feto-maternal allo-immunisation prophylaxis to chronic
      lymphocytic leukaemia therapy].
AB  - The Laboratoire francais du fractionnement et des biotechnologies (LFB), the
      leading manufacturer of plasma-derived medicinal products in France and 6th
      worldwide, is strongly involved in the development of therapeutic monoclonal
      antibodies (mAb). For more than 15 years, LFB has been focusing its research
      effort on the study of structure-function relationship of antibodies. Its studies
      on the molecular basis of IgG interaction with the receptors for the Fc portion
      of IgG (FcgRs) has made it possible to develop antibodies with high antibody
      dependent cellular cytotoxicity (ADCC) activity and enhanced affinity to FcgRIII
      (CD16), both correlated to a glycosylation pattern characterized by a low fucose
      content. Based on these studies, LFB has developed EMABling, a technological
      platform for the production of antibodies with enhanced cytotoxicity ability. Two
      EMABling antibodies recently entered clinical development: LFB-R593, a fully
      human anti-rhesus D (RhD) antibody, for the prevention of feto-maternal allo
      immunization in RhD- women, as a substitute for human polyclonal anti-RhD
      immunoglobulins, and LFB-R603, a monoclonal antibody directed against CD20, for
      the treatment of B cell malignancies. LFB investment in bioproduction through the
      recent acquisition of MAbgene company, a fully integrated French contract
      biopharmaceutical manufacturing company, allows the production of antibodies to a
      large GMP scale. As a whole, LFB owns a portfolio of several EMABling antibodies
      with high therapeutic interest, in line with its public health mission.

PMID- 20035695
TI  - [Recombinant antibodies against bioweapons].
AB  - The threat posed by bioweapons (BW) could lead to the re-emergence of such deadly
      diseases as plague or smallpox, now eradicated from industrialized countries. The
      development of recombinant antibodies allows tackling this risk because these
      recombinant molecules are generally well tolerated in human medicine, may be
      utilized for prophylaxis and treatment, and because antibodies neutralize many
      BW. Recombinant antibodies neutralizing the lethal toxin of anthrax, botulinum
      toxins and the smallpox virus have in particular been isolated recently, with
      different technologies. Our approach, which uses phage-displayed immune libraries
      built from non-human primates (M. fascicularis) to obtain recombinant antibodies,
      which may later be super-humanized (germlinized), has allowed us to obtain such
      BWs-neutralizing antibodies.

PMID- 20035696
TI  - [Transgenesis and humanization of murine antibodies].
AB  - The properties of monoclonal antibodies explain why they are such a successful
      class of therapeutic molecules. However, pionneered initial antibodies were of
      murine origin and triggered an immune response which limited the therapeutic
      potential of the antibody and generated deleterious effects. Consequently,
      tremendous efforts have been developped to engineer these murine Ig by
      introducing human sequences in vitro, or in vivo by humanization of murine
      antibodies, leading to chimeric immunoglobulins, and more recently generation of
      fully human antibodies in transgenic mice with a more or less diversified V
      repertoire. These approaches have led to the development of an increasing number
      of these chimeric or humanized monoclonal antibodies entering pharmaceutical
      pipelines.

PMID- 20035697
TI  - [Bispecific antibodies: what future?].
AB  - Monoclonal antibodies have emerged as a very successful class of therapeutic
      agents. In their native format, monoclonal antibodies are monospecific in that
      they recognize only one epitope, but their Fc domain also binds to FcfR
      expressing cells. Attempts to improve the cytotoxicity of antibodies,
      particularly in the cancer field, have led to the design of bispecific
      antibodies: this can occur through various strategies, such as quadroma,
      thioether-linked Fab' gamma fragments or genetic engineering. Such bispecific
      antibodies have been developped to enhance immunotherapy, by bridging tumor cells
      and T cells, or radioimmunotherapy by combining bispecific antibodies and
      radiolabeled bivalent haptens that bind cooperatively to target cells. Multiple
      further applications can be envisaged such as targeting two different antigens on
      the same cell, or two epitopes of the same antigen. Although progresses have been
      slowed by technical constraints, there is little doubt that this class of novel
      antibodies derivatives will experience a promising development.

PMID- 20035698
TI  - [The future of antibody fragments, made of a single immunoglobulin domain].
AB  - Monoclonal antibodies are now established as key therapeutics for a range of
      diseases including cancer and auto-immunity. However, despite important
      improvements, these molecules still face several serious limitations including
      production costs and tumor penetration. A new class of antibody fragments, made
      of a single immunoglobulin domain, is emerging as an exciting alternative. This
      review describes the outstanding properties and the first achievements of these
      domain antibodies.

PMID- 20035699
TI  - [Alternative production systems for therapeutic monoclonal antibodies].

PMID- 20035700
TI  - [Protein scaffolds as alternatives to whole antibodies: from discovery research
      to clinical development].
AB  - Recent advances in combinatorial protein engineering have made it possible to
      develop non-Ig protein scaffolds that can potentially substitute for most whole
      antibody-associated properties. These protein scaffolds display most of the
      binding properties associated with the variable domain of antibodies. In theory,
      many different natural human protein backbones are suitable to be used as
      recombinant templates for engineering ; in practice however, only a few have
      yielded the necessary properties to be translated into << druggable biologicals
      >>. Amongst these properties, potential broad specificities towards any kind of
      target, ease of production, small size, good tolerability and low immunogenicity
      are essential. Intellectual property is another key issue. In this review, a
      particular emphasis will be given to the most validated non-Ig scaffolds that
      have reached the clinical development phase.

PMID- 20035701
TI  - [Intrabodies, potent tools to unravel the function and dynamics of intracellular
      proteins].
AB  - In the 1980s, progress in molecular biology enabled the manipulation and cloning
      of antibody fragments as functional scFv (single chain Fv). Because of their
      small size and relative ease of expression, scFv opened the road for new medical
      and biotechnological applications. scFvs can be easily expressed and targeted to
      different cellular compartments (cytosol, nucleus, endoplasmic reticulum,
      mitochondria, inner surface of the plasma membrane, etc.), using specific signals
      to target or retain them in a given compartment. Recombinant antibodies can thus
      be used as intracellular antibodies (intrabody) to neutralize, disrupt or track
      endogenous antigen. Intrabodies not only represent new tools for fundamental
      research to study the dynamics of endogenous proteins, but may also bring
      interesting options for applied research in terms of intracellular immunization
      for therapeutic use.

PMID- 20035703
TI  - [Regulatory consequences for the use of monoclonal antibodies].
AB  - Kohler and Milstein published a method for the manufacture of mouse monoclonal
      antibodies of predefined specificity 1975 [1], a work rewarded with the Nobel
      Prize 1984. Since then, the field has developed rapidly with new production
      methods such as recombinant DNA technology, phage display and genetically
      engineered animals. Following the first clinical applications with a mouse
      monoclonal antibody, new classes as chimaeric, humanized and human monoclonal
      antibodies appeared, with the advantages of less adverse reactions and better
      efficacy. The development over more than 30 years resulted in more than 25
      approved products on the market for various therapeutic applications, e.g. for
      the treatment of cancer, inflammatory diseases, heart disease and
      transplantation, and medicines for many more applications are currently under
      development.

PMID- 20035702
TI  - [From orthoclone to denosumab, the fast growing market of monoclonal antibodies].
AB  - Monoclonal antibodies are a specific medicinal category within the current
      therapeutic armamentarium. Their market share is growing fast as they are often
      the only therapeutic option at some stages of certain diseases, due to their
      targeted action in the body and to an acceptable tolerance. The budget impact of
      monoclonal antibodies is increasing, leading payers and health authorities to
      growing attention and pressure when they have to decide on the reimbursement,
      coverage and pricing of these products. The launch of biosimilars after patent
      expiry of some of these drugs will take time in view of the complexity of these
      molecules, and is not likely to significantly impact the cost of these therapies.

PMID- 20035704
TI  - [Therapeutic monoclonal antibodies in the French community: let's get organized].

PMID- 20035705
TI  - [Therapeutic monoclonal antibodies: knowledge transfer from Inserm].

PMID- 20035706
TI  - Preimplantation genetic diagnosis of beta-thalassemia using real-time polymerase
      chain reaction with fluorescence resonance energy transfer hybridization probes.
AB  - Preimplantation genetic diagnosis (PGD) is employed increasingly to allow
      transfer of embryos to the uterus in assisted reproduction procedures. There are
      three stages of biopsy: polar bodies, one or two blastomeres from the cleavage
      stage embryos, and trophectoderm cells ( approximately 5cells) from the
      blastocyst-stage embryos. Validation of polymerase chain reaction (PCR)-based
      assays are challenging because only limited genetic material can be obtained for
      PGD. In the current study, we modified a valid single-cell PCR protocol for PGD
      using real-time PCR assay with fluorescence resonance energy transfer (FRET)
      hybridization probes followed by melting curve analysis. We optimized and
      clinically applied the protocol, permitting molecular genetic analysis to amplify
      a specific region on the beta-globin (HBB) gene for a couple, carriers of two
      mutations: c.-78A>G and c.52A>T. Among a total of eight embryos obtained after
      ovarian stimulation, a single blastomere per embryo at the six- to eight-cell
      stage was biopsied. This PGD method showed that four embryos were unaffected, two
      embryos were selected for transfer, and one pregnancy was achieved. Finally, a
      healthy male baby was delivered at 38weeks' gestation. The results obtained using
      the new method, FRET hybridization probes, were compared with findings using an
      existing method, primer extension minisequencing.

PMID- 20035707
TI  - Mitochondrial calpain system: an overview.
AB  - Calpain system is generally known to be comprised of three molecules: two Ca2+
      dependent proteases: mu- and m-calpains, and their endogenous inhibitor,
      calpastatin. While calpains have previously been considered as the cytoplasmic
      enzymes, research in the recent past demonstrated that mu-calpain, m-calpain and
      calpain 10 are present in mitochondria, which play important roles in a variety
      of pathophysiological conditions including necrotic and apoptotic cell death
      phenomena. Although a number of original research articles on mitochondrial
      calpain system are available, yet to the best of our knowledge, a precise review
      article on mitochondrial calpain system has, however, not been available. This
      review outlines the key features of the mitochondrial calpain system, and its
      roles in several cellular and biochemical events under normal and some
      pathophysiological conditions.

PMID- 20035708
TI  - Protective effect of resveratrol against LPS-induced extracellular
      lipoperoxidation in AR42J cells partly via a Myd88-dependent signaling pathway.
AB  - Lipopolysaccharides (LPS) are major components of the cell wall of Gram negative
      bacteria implicated in the pathogenesis of bacterial infection. Resveratrol is a
      polyphenolic phytoalexin exhibiting antioxidant and anti-inflammatory properties.
      We investigated the protective effects of this natural compound on LPS-induced
      proinflammatory effect using non-myeloid AR42J pancreatic cells. We found that
      LPS dose-dependently increased extracellular malondialdehyde (MDA) and nitric
      oxide without affecting their intracellular level whereas resveratrol abolished
      all these deleterious effects. LPS increased CD14 expression; IRAK1 and a
      phosphorylated form of p38 MAPK protein. Resveratrol counteracted LPS effect by
      decreasing CD14 and IRAK1 expression but unexpectedly increased the p38 MAPK
      protein phosphorylation. Altogether, our data highlighted the functionality of
      the TLR4-Myd88 signaling pathway in LPS pro-oxidant effect using non-myeloid
      cells. They further suggested that resveratrol exerted antioxidant properties
      either by a Myd88-dependent way not involving IRAK1 or by a TRIF dependent
      pathway.

PMID- 20035709
TI  - The plasma membrane Ca2+ pump catalyzes the hydrolysis of ATP at low rate in the
      absence of Ca2+.
AB  - The plasma membrane Ca2+ ATPase catalyzed the hydrolysis of ATP in the presence
      of millimolar concentrations of EGTA and no added Ca2+ at a rate near 1.5% of
      that attained at saturating concentrations of Ca2+. Like the Ca-dependent ATPase,
      the Ca-independent activity was lower when the enzyme was autoinhibited, and
      increased when the enzyme was activated by acidic lipids or partial proteolysis.
      The ATP concentration dependence of the Ca2+-independent ATPase was consistent
      with ATP binding to the low affinity modulatory site. In this condition a small
      amount of hydroxylamine-sensitive phosphoenzyme was formed and rapidly decayed
      when chased with cold ATP. We propose that the Ca2+-independent ATP hydrolysis
      reflects the well known phosphatase activity which is maximal in the absence of
      Ca2+ and is catalyzed by E(2)-like forms of the enzyme. In agreement with this
      idea pNPP, a classic phosphatase substrate was a very effective inhibitor of the
      ATP hydrolysis.

PMID- 20035710
TI  - The main thylakoid membrane lipid monogalactosyldiacylglycerol (MGDG) promotes
      the de-epoxidation of violaxanthin associated with the light-harvesting complex
      of photosystem II (LHCII).
AB  - In higher plants, the major part of the xanthophyll cycle pigment violaxanthin
      (Vx) is non-covalently bound to the main light-harvesting complex of PSII
      (LHCII). Under saturating light conditions Vx has to be released from its binding
      site into the surrounding lipid phase, where it is converted to zeaxanthin (Zx)
      by the enzyme Vx de-epoxidase (VDE). In the present study we investigated the
      influence of thylakoid lipids on the de-epoxidation of Vx, which was still
      associated with the LHCII. We isolated LHCII with different concentrations of
      native, endogenous lipids and Vx by sucrose gradient centrifugation or successive
      cation precipitation. Analysis of the different LHCII preparations showed that
      the concentration of LHCII-associated Vx was correlated with the concentration of
      the main thylakoid lipid monogalactosyldiacylglycerol (MGDG) associated with the
      complexes. Decreases in the MGDG content of the LHCII led to a diminished Vx
      concentration, indicating that a part of the total Vx pool was located in an MGDG
      phase surrounding the LHCII, whereas another part was bound to the LHCII
      apoproteins. We further studied the convertibility of LHCII-associated Vx in in
      vitro enzyme assays by addition of isolated VDE. We observed an efficient and
      almost complete Vx conversion in the LHCII fractions containing high amounts of
      endogenous MGDG. LHCII preparations with low concentrations of MGDG exhibited a
      strongly reduced Vx de-epoxidation, which could be increased by addition of
      exogenous, pure MGDG. The de-epoxidation of LHCII-associated Vx was saturated at
      a much lower concentration of native, endogenous MGDG compared with the
      concentration of isolated, exogenous MGDG, which is needed for optimal VDE
      activity in in-vitro assays employing pure isolated Vx.

PMID- 20035711
TI  - De novo design of a non-natural fold for an iron-sulfur protein: alpha-helical
      coiled-coil with a four-iron four-sulfur cluster binding site in its central
      core.
AB  - Using a 'metal-first' approach, we computationally designed, prepared, and
      characterized a four-iron four-sulfur (Fe(4)S(4)) cluster protein with a non
      natural alpha-helical coiled-coil fold. The novelty of this fold lies in the
      placement of a Fe(4)S(4) cluster within the hydrophobic core of a four-helix
      bundle, making it unique among previous iron-sulfur (FeS) protein designs, and
      different from known natural FeS proteins. The apoprotein, recombinantly
      expressed and purified from E. coli, readily self-assembles with Fe(4)S(4)
      clusters in vitro. UV-Vis absorption and CD spectroscopy, elemental analysis, gel
      filtration, and analytical ultracentrifugation confirm that the protein is folded
      and assembled as designed, namely, alpha-helical coiled-coil binding a single
      Fe(4)S(4) cluster. Dithionite-reduced holoprotein samples have characteristic
      rhombic EPR spectra, typical of low-potential, [Fe(4)S(4)](+) (S=1/2), with g
      values of g(zy)=(1.970, 1.975), and g(x)=2.053. The temperature, and power
      dependence of the signal intensity were also characteristic of [Fe(4)S(4)](+)
      clusters with very efficient spin relaxation, but almost without any interaction
      between adjacent clusters. The new design is very promising although optimization
      is required, particularly for preventing aggregation, and adding second shell
      interactions to stabilize the reduced state. Its main advantage is its
      extendibility into a multi-FeS cluster protein by simply duplicating and
      translating the binding site along the coiled-coil axis. This opens new
      possibilities for designing protein-embedded redox chains that may be used as
      "wires" for coupling any given set of redox enzymes.

PMID- 20035712
TI  - Notch signaling in pancreatic endocrine cell and diabetes.
AB  - Recent studies have improved our understanding of the physiological function of
      Notch signaling pathway and now there is compelling evidence demonstrating that
      Notch is a key regulator of embryonic development and tissue homeostasis.
      Although further extensive studies are necessary to illustrate the molecular
      mechanisms, new insights into the role of Notch signaling in pancreas development
      and diabetes have been achieved. Importantly, the ability to regulate Notch
      signaling intensity both positively and negatively may have therapeutic relevance
      for diabetes. Thus, this paper reviews the current knowledge of the roles of
      Notch signaling in the pancreatic endocrine cell system.

PMID- 20035713
TI  - SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular
      cancer.
AB  - Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or
      lung. However, it remains unclear which genes are associated with TGCT
      metastasis. The aim of this study was to identify gene(s) that promoted human
      TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from
      JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub
      line with high metastatic potential, into mice with JKT-1 xenografts.
      Administration of CM from JKT-HM significantly promoted lymph node metastasis. A
      cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine
      peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted
      protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph
      node metastasis in the xenograft model, compared with administration of CM from
      JKT-HM cells. There was no significant difference in xenograft volume. Moreover,
      administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote
      lymph node metastasis in the xenograft model. There was no difference in the in
      vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM
      cells, compared to that with CM from JKT-1. There was no promotion of
      proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and
      LYVE-1 immunohistochemistry, respectively. Although we could not clarify how
      SERPINE2 promoted lymph node metastasis, it may be a promoter in the development
      of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

PMID- 20035714
TI  - Heat shock protein 60 and adipocytes: characterization of a ligand-receptor
      interaction.
AB  - Adipocyte-derived mediators contribute to chronic, diabetes-associated
      inflammation. We recently demonstrated, that heat shock protein 60 (Hsp60) is an
      effective inductor of inflammatory adipocyte activities. In the present study, we
      characterized the initial Hsp60 binding to adipocyte receptor structures.
      Analyses with preadipocytes and adipocytes from the murine 3T3-L1 line and with
      primary cultures from the New Zealand obese mouse, a model of human obesity,
      revealed comparable specific, dose-dependent and saturable Hsp60 binding,
      confirming the characteristics of a ligand-receptor interaction. Furthermore, we
      identified the N-terminal regions aa1-50 and aa91-110 of the Hsp60 molecule as
      relevant epitopes involved in binding to receptor structures on these cells. Our
      results demonstrate differentiation-independent conserved Hsp60 reactivity in
      permanent and primary adipocytes, strongly indicating that Hsp60 is an important
      regulator of inflammatory adipocyte activities.

PMID- 20035715
TI  - Cooperation of NAD(P)H:quinone oxidoreductase 1 and UDP-glucuronosyltransferases
      reduces menadione cytotoxicity in HEK293 cells.
AB  - Previous studies have shown that NAD(P)H:quinone oxidoreductase 1 (NQO1) plays an
      important role in the detoxification of menadione (2-methyl-1,4-naphthoquinone,
      also known as vitamin K3). However, menadiol (2-methyl-1,4-naphthalenediol)
      formed from menadione by NQO1-mediated reduction continues to be an unstable
      substance, which undergoes the reformation of menadione with concomitant
      formation of reactive oxygen species (ROS). Hence, we focused on the roles of
      phase II enzymes, with particular attention to UDP-glucuronosyltransferases
      (UGTs), in the detoxification process of menadione. In this study, we established
      an HEK293 cell line stably expressing NQO1 (HEK293/NQO1) and HEK293/NQO1 cell
      lines with doxycycline (DOX)-regulated expression of UGT1A6 (HEK293/NQO1/UGT1A6)
      and UGT1A10 (HEK293/NQO1/UGT1A10), and evaluated the role of NQO1 and UGTs
      against menadione-induced cytotoxicity. Our results differed from those of
      previous studies. HEK293/NQO1 was the most sensitive cell line to menadione
      cytotoxicity among cell lines established in this study. These phenomena were
      also observed in HEK293/NQO1/UGT1A6 and HEK293/NQO1/UGT1A10 cells in which the
      expression of UGT was suppressed by DOX treatment. On the contrary,
      HEK293/NQO1/UGT1A6 and HEK293/NQO1/UGT1A10 cells without DOX treatment were
      resistant to menadione-induced cytotoxicity. These results demonstrated that NQO1
      is not a detoxification enzyme for menadione and that UGT-mediated
      glucuronidation of menadiol is the most important detoxification process.

PMID- 20035716
TI  - Biochemical characterization of GDP-L-fucose de novo synthesis pathway in fungus
      Mortierella alpina.
AB  - Mortierella alpina is a filamentous fungus commonly found in soil, which is able
      to produce large amount of polyunsaturated fatty acids. L-fucose is an important
      sugar found in a diverse range of organisms, playing a variety of biological
      roles. In this study, we characterized the de novo biosynthetic pathway of GDP-L
      fucose (the nucleotide-activated form of L-fucose) in M. alpina. Genes encoding
      GDP-D-mannose 4,6-dehydratase (GMD) and GDP-keto-6-deoxymannose 3,5-epimerase/4
      reductase (GMER) were expressed heterologously in Escherichia coli. The
      recombinant enzymes were produced as His-tagged fusion proteins. Conversion of
      GDP-mannose to GDP-4-keto-6-deoxy mannose by GMD and GDP-4-keto-6-deoxy mannose
      to GDP-L-fucose by GMER were analyzed by capillary electrophoresis, electro-spray
      ionization-mass spectrometry, and nuclear magnetic resonance spectroscopy. The
      k(m) values of GMD for GDP-mannose and GMER for GDP-4-keto-6-deoxy mannose were
      determined to be 0.77 mM and 1.047 mM, respectively. Both NADH and NADPH may be
      used by GMER as the coenzyme. The optimum temperature and pH were determined to
      be 37 degrees C and pH 9.0 (GMD) or pH 7.0 (GMER). Divalent cations are not
      required for GMD and GMER activity, and the activities of both enzymes may be
      enhanced by DTT. To our knowledge this is the first report on the
      characterization of GDP-L-fucose biosynthetic pathway in fungi.

PMID- 20035717
TI  - Rmt1 catalyzes zinc-finger independent arginine methylation of ribosomal protein
      Rps2 in Saccharomyces cerevisiae.
AB  - Rps2/rpS2 is a well conserved protein of the eukaryotic ribosomal small subunit.
      Rps2 has previously been shown to contain asymmetric dimethylarginine residues,
      the addition of which is catalyzed by zinc-finger-containing arginine
      methyltransferase 3 (Rmt3) in the fission yeast Schizosaccharomyces pombe and
      protein arginine methyltransferase 3 (PRMT3) in mammalian cells. Here, we
      demonstrate that despite the lack of a zinc-finger-containing homolog of
      Rmt3/PRMT3 in the budding yeast Saccharomyces cerevisiae, Rps2 is partially
      modified to generate asymmetric dimethylarginine and monomethylarginine residues.
      We find that this modification of Rps2 is dependent upon the major arginine
      methyltransferase 1 (Rmt1) in S. cerevisiae. These results are suggestive of a
      role for Rmt1 in modifying the function of Rps2 in a manner distinct from that
      occurring in S. pombe and mammalian cells.

PMID- 20035718
TI  - BRE over-expression promotes growth of hepatocellular carcinoma.
AB  - BRE, also known as TNFRSF1A modulator and BRCC45, is an evolutionarily highly
      conserved protein. It is a death receptor-associated protein in cytoplasm and a
      component of BRCA1/2-containing DNA repair complex in nucleus. BRE was found to
      have anti-apoptotic activity. Over-expression of BRE by transfection promoted
      survival of cell lines against apoptotic induction; whereas depletion of the
      protein by siRNA resulted in the opposite. In vivo anti-apoptotic activity of BRE
      was demonstrated by significant attenuation of Fas-induced acute fulminant
      hepatitis in transgenic mice expressing the human protein specifically in the
      liver. BRE was also implicated in tumor promotion by the accelerated tumor growth
      of Lewis Lung carcinoma transfected with human BRE; and by high expression of BRE
      specifically in the tumoral regions of human hepatocellular carcinoma (HCC). The
      present study was to test directly if transgenic expression of BRE in livers
      could promote HCC development in neonatal diethylnitrosamine model. By 8months
      after tumor induction, the maximal sizes of tumor nodules of transgenic mice were
      significantly larger than those of the non-transgenic controls, although the
      numbers of tumor nodules between the two groups did not significantly differ.
      Importantly, as in human HCC, the mouse endogenous BRE level was up-regulated in
      mouse HCC nodules. These results show that BRE over-expression can indeed promote
      growth, though not initiation, of liver tumors. Furthermore, the common
      occurrence of BRE over-expression in human and mouse HCC suggests that up
      regulation of BRE is functionally important in liver tumor development.

PMID- 20035719
TI  - Caspase 3 inactivates biologically active full length interleukin-33 as a
      classical cytokine but does not prohibit nuclear translocation.
AB  - IL-33 is a member of the IL-1 family of cytokines with dual function which either
      activates cells via the IL-33 receptor in a paracrine fashion or translocates to
      the nucleus to regulate gene transcription in an intracrine manner. We show that
      full length murine IL-33 is active as a cytokine and that it is not processed by
      caspase 1 to mature IL-33 but instead cleaved by caspase 3 at aa175 to yield two
      products which are both unable to bind to the IL-33 receptor. Full length IL-33
      and its N-terminal caspase 3 breakdown product, however, translocate to the
      nucleus. Finally, bioactive IL-33 is not released by cells constitutively or
      after activation. This suggests that IL-33 is not a classical cytokine but exerts
      its function in the nucleus of intact cells and only activates others cells via
      its receptor as an alarm mediator after destruction of the producing cell.

PMID- 20035720
TI  - DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A
      novel agent for drug eluting stents?
AB  - BACKGROUND: DMSO is routinely infused together with hematopoietic cells in
      patients undergoing myeloablative therapy and was recently found to inhibit
      smooth muscle cells proliferation and arterial thrombus formation in the mouse by
      preventing tissue factor (TF), a key activator of the coagulation cascade. This
      study was designed to investigate whether DMSO prevents platelet activation and
      thus, whether it may represent an interesting agent to be used on drug eluting
      stents. METHODS AND RESULTS: Human venous blood from healthy volunteers was
      collected in citrated tubes and platelet activation was studied by cone and
      platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis
      showed that DMSO-treated platelets exhibit a lower adherence in response to shear
      stress (-15.54+/-0.9427%, n=5, P<0.0001 versus control). Additionally,
      aggregometry studies revealed that DMSO-treated, arachidonate-stimulated
      platelets had an increased lag phase (18.0%+/-4.031, n=9, P=0.0004 versus
      control) as well as a decreased maximal aggregation (-6.388+/-2.212%, n=6,
      P=0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous
      thromboxane A2 and was mediated, at least in part, by COX-1 inhibition.
      CONCLUSIONS: Clinically relevant concentrations of DMSO impair platelet
      activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may
      be crucial for the previously reported anti-thrombotic property displayed by
      DMSO. Our findings support a role for DMSO as a novel drug to prevent not only
      proliferation, but also thrombotic complications of drug eluting stents.

PMID- 20035721
TI  - NBBA, a synthetic small molecule, inhibits TNF-alpha-induced angiogenesis by
      suppressing the NF-kappaB signaling pathway.
AB  - Nuclear factor-kappaB (NF-kappaB) is a crucial transcription factor that
      contributes to cancer development by regulating a number of genes involved in
      angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3
      oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene)propan-2-amine oxide (NBBA) as a
      new anti-angiogenic small molecule that targets NF-kappaB activity. NBBA showed
      stronger growth inhibition on human umbilical vein endothelial cells (HUVECs)
      than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis
      factor-alpha (TNF-alpha)-induced tube formation and invasion of HUVECs. In
      addition, NBBA suppressed the neovascularization of chorioallantonic membrane
      from growing chick embryos in vivo. To address the mode of action of the
      compound, the effect of NBBA on TNF-alpha-induced NF-kappaB transcription
      activity was investigated. NBBA suppressed TNF-alpha-induced c-Jun N-terminal
      kinase phosphorylation, which resulted in suppression of transcription of NF
      kappaB and its target genes, including interleukin-8, interleukin-1alpha, and
      epidermal growth factor. Collectively, these results demonstrated that NBBA is a
      new anti-angiogenic small molecule that targets the NF-kappaB signaling pathway.

PMID- 20035722
TI  - An epigenetic mechanism for capecitabine resistance in mesothelioma.
AB  - Mesothelioma is an uncommon malignancy whose global incidence continues to rise.
      The therapeutic standard for advanced disease is intravenous pemetrexed and
      cisplatin. The anti-folate capecitabine is significantly less effective than
      pemetrexed. The balance between thymidylate synthase (TS), dihydropyrimidine
      dehydrogenase (DPD), and thymidine phosphorylase (TP) is critical to the efficacy
      of capecitabine. DNA from mesothelioma cell lines was bisulfite treated and
      examined by MS-PCR, RNA was obtained for real-time PCR analysis, and protein
      lysates were obtained for Western immunoblot analysis. Cytotoxicity was assessed
      by MTT assay, comparing 5-aza-CdR pretreated or untreated cells with 5'-deoxy-5
      fluorouridine (DFUR), 5-FU, and pemetrexed. Finally bisulfite sequencing of the
      extracellular growth factor-1 (ECGF-1) gene was performed on 4 mesothelioma
      samples and pericardial tissue. One of the four cell lines tested (H290) was
      methylated for ECGF-1. This corresponded to a lack of TP expression by real-time
      PCR and Western immunoblot. Treatment with 1muM 5-aza-CdR increased TP mRNA and
      protein expression in H290. DFUR, the substrate for TP, showed increased
      cytotoxicity when delivered after 5-aza-CdR exposure in the methylated cell line.
      There was no difference in any of the unmethylated cell lines when cells were
      exposed to 5-FU or pemetrexed with or without 5-aza-CdR. Patient tumor samples
      revealed an increased number of methylated CpG sites in ECGF-1 compared to normal
      pericardium. Methylation of ECGF-1, leads to transcriptional silencing of TP and
      may explain the lack of any effect of capecitabine, especially when compared to
      pemetrexed.

PMID- 20035723
TI  - Characterization of a novel non-steroidal glucocorticoid receptor antagonist.
AB  - Selective antagonists of the glucocorticoid receptor (GR) are desirable for the
      treatment of hypercortisolemia associated with Cushing's syndrome, psychic
      depression, obesity, diabetes, neurodegenerative diseases, and glaucoma. NC3327,
      a non-steroidal small molecule with potent binding affinity to GR (K(i)=13.2nM),
      was identified in a high-throughput screening effort. As a full GR antagonist,
      NC3327 greatly inhibits the dexamethasone (Dex) induction of marker genes
      involved in hepatic gluconeogenesis, but has a minimal effect on matrix
      metalloproteinase 9 (MMP-9), a GR responsive pro-inflammatory gene.
      Interestingly, the compound recruits neither coactivators nor corepressors to the
      GR complex but competes with glucocorticoids for the interaction between GR and a
      coactivator peptide. Moreover, NC3327 does not trigger GR nuclear translocation,
      but significantly blocks Dex-induced GR transportation to the nucleus, and thus
      appears to be a 'competitive' GR antagonist. Therefore, the non-steroidal
      compound, NC3327, may represent a new class of GR antagonists as potential
      therapeutics for a variety of cortisol-related endocrine disorders.

PMID- 20035725
TI  - Structural characterization of the intra-membrane histidine kinase YbdK from
      Bacillus subtilis in DPC micelles.
AB  - Bacterial histidine kinases (HKs) play a critical role in signal transduction for
      cellular adaptation to environmental conditions and stresses. YbdK from Bacillus
      subtilis is a 320-residue intra-membrane sensing HK characterized by a short
      input domain consisting of two transmembrane helices without an extracytoplasmic
      domain. While the cytoplasmic domains of HKs have been studied in detail, the
      intra-membrane sensing domain systems are still uncharacterized due to
      difficulties in handling the transmembrane domain. Here, we successfully obtained
      pure recombinant transmembrane domain of YbdK (YbdK-TM) from E. coli and analyzed
      the characteristics of YbdK-TM using nuclear magnetic resonance (NMR) and other
      biophysical methods. YbdK-TM was found to form homo-dimers in DPC micelles based
      on cross-linking assays and analytical ultracentrifugation analyses. We estimated
      the size of the YbdK-TM DPC complex to be 46kDa using solution state NMR
      T(1)/T(2) relaxation analyses in DPC micelles. These results provide information
      that will allow functional and structural studies of intra-membrane sensing HKs
      to begin.

PMID- 20035724
TI  - Altered dopamine transporter function and phosphorylation following chronic
      cocaine self-administration and extinction in rats.
AB  - Cocaine binds with the dopamine transporter (DAT), an effect that has been
      extensively implicated in its reinforcing effects. However, persisting
      adaptations in DAT regulation after cocaine self-administration have not been
      extensively investigated. Here, we determined the changes in molecular mechanisms
      of DAT regulation in the caudate-putamen (CPu) and nucleus accumbens (NAcc) of
      rats with a history of cocaine self-administration, followed by 3weeks of
      withdrawal under extinction conditions (i.e., no cocaine available). DA uptake
      was significantly higher in the CPu of cocaine-experienced animals as compared to
      saline-yoked controls. DAT V(max) was elevated in the CPu without changes in
      apparent affinity for DA. In spite of elevated CPu DAT activity, total and
      surface DAT density and DAT-PP2Ac (protein phosphatase 2A catalytic subunit)
      interaction remained unaltered, although p-Ser- DAT phosphorylation was elevated.
      In contrast to the CPu, there were no differences between cocaine and saline rats
      in the levels of DA uptake, DAT V(max) and K(m) values, total and surface DAT, p
      Ser-DAT phosphorylation, or DAT-PP2Ac interactions in the NAcc. These results
      show that chronic cocaine self-administration leads to lasting, regionally
      specific alterations in striatal DA uptake and DAT-Ser phosphorylation. Such
      changes may be related to habitual patterns of cocaine-seeking observed during
      relapse.

PMID- 20035726
TI  - The gelsolin:calponin complex nucleates actin filaments with distinct
      morphologies.
AB  - Gelsolin and calponin are cytoskeletal and signalling proteins that form a tight
      1:1 complex (GCC). We show that calponin within the GCC inhibits the rate of
      gelsolin mediated nucleation of actin polymerization. The actin-binding function
      of calponin is ablated within the GCC as the actin-binding site overlaps with one
      of the gelsolin binding sites. The structure of filaments that result from
      nucleation by GCC are different to those nucleated by gelsolin alone in that they
      are longer, loosely bundled and stain heterogeneously with phalloidin. GCC
      nucleated filaments appear contorted and wrap around each to form the loose
      bundles.

PMID- 20035727
TI  - Benzene as a cause of lymphoproliferative disorders.
AB  - There is a long standing issue concerning the strength of evidence relating
      benzene to lymphocytic neoplasms. Because benzene is a known cause of human acute
      myelogenous leukemia there has been little reason for organizations such as the
      International Agency for Research on Cancer (IARC) or the US National Toxicology
      Program (NTP) to perform standard hazard identification reviews of benzene as a
      possible cause of other cancers such as lymphomas. Increased understanding of
      underlying mechanisms of carcinogenesis, as is reflected in the greater scope
      given to mechanistic evidence in assigning overall sufficiency of evidence for
      carcinogenicity by both IARC and NTP, suggests that the evidence supporting
      benzene as a cause of lymphoma likely has passed the threshold required for being
      listed as a known causal relationship. A broad range of genotoxic effects in the
      lymphocytes of benzene-exposed workers has been well documented, as has the role
      of chromosomal effects in carcinogenesis. There is also increasing evidence of a
      close relationship between lymphoid tumors and the types of myeloid tumors known
      to be caused by benzene. This includes the not infrequent finding of biphenotypic
      lineage as well as the formation of lymphoid as well as myeloid leukemias
      following chemotherapy. Studies of the mechanism of benzene toxicity are
      consistent with a relatively non-specific mechanism capable of producing multiple
      chromosomal changes, and there is evidence that the early hematopoietic stem
      cell, which is believed to be targeted by benzene in causing myeloid cancers, is
      also the progenitor of lymphocytic cell types. Furthermore, the classification of
      lymphomas has evolved so that non-Hodgkin lymphoma now includes such formerly
      distinct disorders as chronic lymphocytic leukemia and multiple myeloma, and
      there is less of a distinction between leukemia and non-leukemia forms of
      lymphoma.

PMID- 20035728
TI  - Hprt mutant frequency and p53 gene status in mice chronically exposed by
      inhalation to benzene.
AB  - Hprt mutant frequency and p53 gene status were assessed in wild-type and p53
      heterozygous (p53+/-) mice exposed chronically by inhalation to benzene. Benzene
      exposures to 100 ppm for 6h on Monday-Friday, 100 ppm for 10h on Monday-Wednesday
      Friday, or 200 ppm for 5h on Monday-Wednesday-Friday yielded the same total
      exposures (concentration x time) of 3000 ppm x h/week. Hprt mutations in splenic
      T-lymphocytes were significantly increased in all benzene groups, ranging from
      3.8- to 8.0-fold greater than control values. Wild-type and p53+/- mice were
      equally susceptible to benzene mutagenesis. Hprt wild-type and mutant isolates
      from control and exposed animals were examined for TCR gene rearrangements (as
      markers of in vivo clonality) and for loss of p53 wild-type or mutant alleles.
      Moderate clonal amplifications were observed among the Hprt mutant but not Hprt
      wild-type isolates but was not sufficient to account for the increases in Hprt
      mutant frequencies. Most isolates, whether Hprt wild-type or mutant, retained
      both p53 alleles in the benzene-exposed p53+/- animals (54% and 63%,
      respectively, for the Hprt wild-type and mutants). However, 37% of the Hprt wild
      type isolates and 46% of the Hprt mutant isolates lost the p53 mutant allele.
      Only a small percentage of either type of isolate lost the p53 wild-type allele,
      and this was always in isolates that that previously lost the p53 mutant allele.
      Loss of the p53 mutant allele was independent of benzene exposure, Hprt status,
      or 6-thioguanine selection. These findings contrast with the p53 status of thymic
      lymphomas that had preferentially lost the wild-type p53 allele in some of these
      same mice. Possible reasons for loss of the mutant p53 allele in the Hprt mutant
      and wild-type isolates are discussed.

PMID- 20035729
TI  - Kinetics and mechanism of inhibition of serine esterases by fluorinated
      aminophosphonates.
AB  - This paper reviews previously published data and presents new results to address
      the hypothesis that fluorinated aminophosphonates (FAPs),
      (RO)(2)P(O)C(CF(3))(2)NHS(O)(2)C(6)H(5), R=alkyl, inhibit serine esterases by
      scission of the P-C bond. Kinetics studies demonstrated that FAPs are progressive
      irreversible inhibitors of acetylcholinesterase (AChE, EC 3.1.1.7.),
      butyrylcholinesterase (BChE, EC 3.1.1.8.), carboxylesterase (CaE, EC 3.1.1.1.),
      and neuropathy target esterase (NTE, EC 3.1.1.5.), consistent with P-C bond
      breakage. Chemical reactivity experiments showed that diMe-FAP and diEt-FAP react
      with water to yield the corresponding dialkylphosphates and
      (CF(3))(2)CHNHS(O)(2)C(6)H(5), indicating lability of the P-C bond. X-ray
      crystallography of diEt-FAP revealed an elongated (and therefore weaker) P-C bond
      (1.8797 (13)A) compared to P-C bonds in dialkylphosphonates lacking alpha-CF(3)
      groups (1.805-1.822A). Semi-empirical and non-empirical molecular modeling of
      diEt-FAP and (EtO)(2)P(O)C(CH(3))(2)NHS(O)(2)C(6)H(5) (diEt-AP), which lacks
      CF(3) groups, indicated lengthening and destabilization of the P-C bond in diEt
      FAP compared to diEt-AP. Active site peptide adducts formed by reacting diEt-FAP
      with BChE and diBu-FAP with NTE catalytic domain (NEST) were identified using
      peptide mass mapping with mass spectrometry (MS). Mass shifts (mean+/-SE, average
      mass) for peaks corresponding to active site peptides with diethylphosphoryl and
      monoethylphosphoryl adducts on BChE were 136.1+/-0.1 and 108.0+/-0.1Da,
      respectively. Corresponding mass shifts for dibutylphosphoryl and
      monobutylphosphoryl adducts on NEST were 191.8+/-0.2 and 135.5+/-0.1Da,
      respectively. Each of these values was statistically identical to the theoretical
      mass shift for each dialkylphosphoryl and monoalkylphosphoryl species. The MS
      results demonstrate that inhibition of BChE and NEST by FAPs yields
      dialkylphosphoryl and monoalkylphosphoryl adducts, consistent with
      phosphorylation via P-C bond cleavage and aging by net dealkylation. Taken
      together, predictions from enzyme kinetics, chemical reactivity, X-ray
      crystallography, and molecular modeling were confirmed by MS and support the
      hypothesis that FAPs inhibit serine esterases via scission of the P-C bond.

PMID- 20035731
TI  - Microscopic structure of heterogeneous lipid-based formulations revealed by 13C
      high-resolution solid-state and 1H PFG NMR methods.
AB  - Lipid-based formulations such as lip glosses that are very alike on the base of
      their components may have significant differences in their expected macroscopic
      properties as cosmetics. To differentiate such formulations, high-resolution
      (13)C NMR was performed under magic angle spinning to investigate the properties
      at both molecular and microscopic levels. Temperature studies were carried out
      and no polymorphism in the solid domains could be evidenced after the thermal
      treatment performed for obtaining the commercial lip glosses. (13)C NMR spectra
      also showed that some waxes remain partially solubilized in the oils of
      formulations. The microscopic structure of the wax-oil liquid domains was worked
      out on the basis of restricted diffusion properties obtained with proton pulsed
      field gradient NMR. Changing a single wax component, in two identical
      formulations, yields significant morphological differences. In the first one the
      liquid phase appears as a continuum whereas in the second one, the liquid phase
      is fractionated into micrometric droplets.

PMID- 20035730
TI  - Benzene-induced bone-marrow toxicity: a hematopoietic stem-cell-specific, aryl
      hydrocarbon receptor-mediated adverse effect.
AB  - Benzene-induced hematopoietic toxicity is an aryl hydrocarbon receptor (AhR)
      related adverse effect that is not exhibited in AhR-knockout (KO) mice. In the
      hematopoietic system, the steady-state expression of AhRs is limited in the
      hematopoietic progenitor cells; thus, a hierarchical hematopoietic impairment
      starts from hematopoietic progenitor cells after benzene exposure. When one looks
      at wild-type recipient mice that have been lethally irradiated and repopulated
      with AhR-KO bone marrow cells, owing to reconstruction by the marrow from AhR-KO
      mice, no impairment is observed in the assay of granulo-macrophage colony-forming
      units (CFU-GMs) in the bone marrow after benzene exposure of the reconstituted
      mice. In contrast, in mature white blood cells concern, benzene-induced
      hematopoietic cytotoxicity is observed in the same reconstituted mice; however,
      this benzene-induced hematopoietic cytotoxicity in mature white blood cells is
      not induced in the case of AhR-KO mice repopulated with wild-type bone marrow
      cells after a lethal dose of irradiation. The mechanism of benzene-induced
      hematopoietic toxicity in the mature blood cells in AhR-KO mice is assumed to be
      based on metabolites such as phenol and hydroquinone derived from hepatic AhR.
      Thus, the former toxicity in mature white blood cells is assumed to be based on
      the metabolites of the wild-type hepatic AhR, whereas the latter lack of toxicity
      in mature blood cells in AhR-KO mice is due to the lack of benzene-induced
      metabolism in the liver. Global gene expression analysis of bone marrow cells
      after benzene exposure reveals that MEF2c, the functions of which are known to
      maintain lymphocyte differentiation and promote proliferation of hematopoietic
      progenitor cells, is commonly downmodulated not only in C57BL/6 but also in
      C3H/He mice. In response to these impairments of the hematopoietic progenitor
      cells and the niches, stochastic and reciprocal upregulations of integrin beta 2
      and the Runx family are observed, which are known to stabilize hematopoietic
      niches during the steady-state. Direct observation of the hematopoietic
      progenitor cells, particularly the Lin(-)c-kit(+)Sca-1(+) (LKS) fraction, after
      benzene exposure revealed an increased amount of intracytoplasmic reactive oxygen
      species (ROS) detected by ROS-reacting dye as compared with other blood cell
      fractions.

PMID- 20035732
TI  - Urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a specific marker of
      oxidative stress, using direct, isocratic LC-MS/MS: Method evaluation and
      application in study of biological variation in healthy adults.
AB  - BACKGROUND: Urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a specific
      biomarker of oxidative stress. We evaluated a modified LC-MS/MS assay for urine 8
      oxodG and determined biological variation in healthy adults. METHOD: Untreated
      urine was injected into an isocratic LC-MS/MS system (positive-ion MRM mode).
      Urine 8-oxodG in 51 healthy volunteers was measured; within- and between-day
      variations in 23 healthy volunteers were investigated. RESULTS: Dose-response was
      linear to 452 nmol/l; limit of detection=2.3 nmol/l; within-run and between-run
      CVs were <3.0% and <4.7%, respectively; recovery=97%-101%; accuracy=97.7-103.5%.
      Urine 8-oxodG (median, mean [SD]): 1.70, 1.70[0.60]nmol/mmol creatinine (n=51).
      Men had higher (p=0.027) concentrations than women matched for age and body mass
      index: mean [SD]: 1.90[1.60]; n=26 vs. 1.50[0.55]; n=25. Within- and between-day
      variations were wide but random. No significant differences were seen overall
      across time-points within 1 day or at the same time-point across 5 consecutive
      days. CONCLUSIONS: The method has advantages of speed and relative simplicity as
      it does not require sample pre-treatment for 8-oxodG extraction, the use of
      internal standard or gradient LC elution and has high linearity, specificity,
      precision and recovery. Biological variation in urine 8-oxodG is wide, but no
      within- or between-day differences at the group concentration were seen in
      healthy adults.

PMID- 20035733
TI  - Mitochondrial DNA damage in spinal and bulbar muscular atrophy patients and
      carriers.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) damage may be involved in the pathogenesis
      of spinal and bulbar muscular atrophy (SBMA). METHODS: We recruited 20 SBMA
      patients, 20 SBMA female carriers, and 20 normal age-matched subjects.
      Mitochondrial DNA damage in the 3 groups of subjects was evaluated using three
      novel mtDNA oxidative markers: mtDNA copy number, 4977 bp deletion of mtDNA
      (mtDNA4977) and oxidative modification of mtDNA index (mtDNA(DeltaCT)) in
      leukocytes. RESULTS: Decreased leukocyte mtDNA copy number, increased
      mtDNA(DeltaCT) value, and increased frequency of mtDNA4977 which correspond to
      the number of CAG repeats in the mutated androgen receptor gene, were found not
      only in SBMA patients but also in female carriers. CONCLUSIONS: Leukocyte mtDNA
      copy number, mtDNA(DeltaCT) and mtDNA4977 may serve as useful biomarkers of mtDNA
      damage and can be used to monitor SBMA disease progression.

PMID- 20035734
TI  - Rapid detection of solute carrier family 4, member 1 (SLC4A1) mutations and
      polymorphisms by high-resolution melting analysis.
AB  - OBJECTIVE: The objective of this study is to develop and evaluate a high
      resolution melting (HRM) method for detection of SLC4A1 mutations and
      polymorphisms. DESIGN AND METHODS: The HRM method was optimized for detection of
      18 known SLC4A1 variants. It was then used for analysis of 16 blind DNA samples
      highly enriched with two common mutations, Southeast Asian ovalocytosis (SAO) and
      band 3 Bangkok 1 (G701D), to compare the results with that of the conventional
      procedures. RESULTS: The HRM method was able to detect all 18 SLC4A1 variants. In
      the samples in which homozygous wild-type and homozygous variant could not be
      distinguished by difference plots, they were spiked with a sample carrying known
      homozygous genotype, resulting in their clear differentiation. The HRM method had
      100% efficiency for detection of mutations in the blind DNA samples, when
      compared with that of the conventional techniques. CONCLUSIONS: The developed HRM
      method is efficient and reproducible for detection of SLC4A1 mutations and
      polymorphisms.

PMID- 20035735
TI  - Construction of an amperometric triglyceride biosensor using PVA membrane bound
      enzymes.
AB  - OBJECTIVES: A method is described for construction of an amperometric
      triglyceride (TG) biosensor using PVA membrane bound enzymes. DESIGN AND METHODS:
      A mixture of commercial lipase, glycerol kinase, glycerol-3-phosphate oxidase and
      horseradish peroxidase was co-immobilized onto polyvinyl alcohol (PVA) membrane
      through glutaraldehyde coupling. The biosensor measures current when polarized at
      0.4 V. RESULTS: The sensor showed optimum response within 2 s at pH 7.0 and 25
      degrees C. The current (mA) was in proportion to concentration of TG in the range
      0.56-2.25 mM. The minimum detection limit of the method was 0.21 mM. The analytic
      recovery of added TG was 94.3%. Within batch and between batch coefficients of
      variations (CV) were <5.85% and <4.13%, respectively. A good correlation (r=0.99)
      was found. Among various serum substances tested, only cholesterol caused slight
      stimulation (20%). CONCLUSIONS: An amperometric method was developed for
      determination of TG employing this enzyme electrode.

PMID- 20035737
TI  - Lmx1a and Lmx1b cooperate with Foxa2 to coordinate the specification of
      dopaminergic neurons and control of floor plate cell differentiation in the
      developing mesencephalon.
AB  - Mesencephalic dopaminergic (mesDA) neurons control movement and behavior, and
      their loss causes severe neurological disorders, such as Parkinson's disease.
      Recent studies have revealed that mesDA neurons originate from mesencephalic
      floor plate (FP) cells, which had been thought of as non-neurogenic organizer
      cells regulating regional patterning and axonal projections. Otx2 and its FP
      specific downstream factor Lmx1a have been shown to be sufficient to confer
      neurogenic activity on FP cells and determine a mesDA fate. However, the
      mechanism underlying how these factors control mesDA development and how FP cells
      and mesDA neurons are coordinately specified are still largely unknown. In the
      present study, we obtained evidence that Lmx1a and Lmx1b cooperate with Foxa2 to
      specify mesDA neuron identity by gain-of-function approaches using transgenic
      mice. Lmx1a/b appeared to select a mesDA fate by suppressing red nucleus fate in
      the context of Foxa2-positive progenitors, at least in part, through repressing
      the Sim1-Lhx1 and Ngn1 pathways that inhibit proper mesDA differentiation. We
      also found that, in the mesencephalon, FP cell fate is primarily determined by
      Foxa2 with a supportive action of Lmx1a/b through repressing Nkx6.1, which
      inhibits FP cell differentiation. Thus, FP and mesDA identities are determined by
      distinct specification pathways, both of which are controlled by the same
      combination of transcription factors, Lmx1a/b and Foxa2, and, as a consequence,
      mesDA neurons are generated from mesencephalic FP cells.

PMID- 20035736
TI  - Signal strength and signal duration define two distinct aspects of JNK-regulated
      axon stability.
AB  - Signaling proteins often control multiple aspects of cell morphogenesis. Yet the
      mechanisms that govern their pleiotropic behavior are often unclear. Here we show
      activity levels and timing mechanisms determine distinct aspects of Jun N
      terminal kinase (JNK) pathway dependent axonal morphogenesis in Drosophila
      mushroom body (MB) neurons. In the complete absence of Drosophila JNK (Basket),
      MB axons fail to stabilize, leading to their subsequent degeneration. However,
      with a partial loss of Basket (Bsk), or of one of the upstream JNK kinases,
      Hemipterous or Mkk4, these axons overextend. This suggests that Bsk activity
      prevents axons from destabilizing, resulting in degeneration and overextension
      beyond their terminal targets. These distinct phenotypes require different
      threshold activities involving the convergent action of two distinct JNK kinases.
      We show that sustained Bsk signals are essential throughout development and act
      additively but are dispensable at adulthood. We also suggest that graded Bsk
      inputs are translated into AP-1 transcriptional outputs consisting of Fos and Jun
      proteins.

PMID- 20035738
TI  - Opposing effects of tenidap on the volume-regulated anion channel and K(ATP)
      channel activity in rat pancreatic beta-cells.
AB  - Tenidap (5-chloro-2-hydroxy-3-(thiophene-2-carbonyl)indole-1-carboxamide) is a
      non-steroidal anti-inflammatory and anti-rheumatic drug with several cellular
      actions including inhibition of anion transport processes. Since other anion
      transport inhibitors have been shown to inhibit activity of the volume-regulated
      anion channel (VRAC), the present study investigated the effects of tenidap on
      activity of this channel in pancreatic beta-cells. Membrane potential, VRAC
      currents and input conductance were recorded from single rat beta-cells in
      primary culture using perforated patch, conventional whole-cell and cell-attached
      configurations of the patch-clamp technique. Relative cell volume was measured
      using a video-imaging method. Tenidap (0.1mM) was found to rapidly hyperpolarise
      the beta-cell membrane potential and terminate glucose-induced electrical
      activity. This effect was associated with a pronounced outward current shift at a
      holding potential of -65mV. Tenidap was found to inhibit activity of the volume
      regulated anion channel with IC(50) values of 31 and 43microM for outward and
      inward currents respectively. Tenidap also markedly increased beta-cell input
      conductance, representing an activation of the K(ATP) conductance. beta-cell
      regulatory volume decrease following hypotonically-induced cell swelling was
      sensitive to inhibition by 50microM tenidap. Tenidap is a potent inhibitor of the
      volume-regulated anion channel and K(ATP) channel activator in rat pancreatic
      beta-cells. These actions could at least in part explain the recently reported
      inhibitory actions of the drug on electrical and secretory activity in the beta
      cell, and could also underlie other pharmacological actions of the drug.

PMID- 20035739
TI  - Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a
      link between diabetes and Alzheimer's disease.
AB  - Type 2 diabetes has been identified as a risk factor for patients with
      Alzheimer's disease. Insulin signalling is often impaired in Alzheimer's disease,
      contributing to the neurodegenerative process. One potential strategy to help
      prevent this is the normalisation of insulin signalling in the brain. Therefore,
      the present study was designed to test the effects of novel enzyme-resistant
      analogues of the insulin-releasing incretin hormone, glucagon-like peptide 1 (GLP
      1). The effects of Liraglutide (Victoza) and other novel GLP-1 analogues were
      tested on synaptic plasticity (LTP) in area CA1 of the hippocampus. At a dose of
      15nmol in 5microl i.c.v., Liraglutide (P<0.005), Asp(7)GLP-1 (P<0.001), N-glyc
      GLP-1 (P<0.01), and Pro(9)GLP-1 (P<0.001). In contrast, the GLP-1 receptor
      antagonist exendin(9-39)amide impaired LTP (P<0.001). Co-injection of exendin(9
      39) and Liraglutide showed no effect on LTP. These results clearly demonstrate
      that Liraglutide and other GLP-1 analogues elicit effects on neurotransmission in
      the brain. Furthermore, GLP-1 peptides are not only effective in modulating
      insulin-release and achieving glycaemic control in type 2 diabetes, but are also
      effective in modulating synaptic plasticity. These findings are consistent with
      our previous observations that the novel analogue (Val(8))GLP-1 enhances LTP and
      reverses the impairments of LTP induced by beta-amyoid fragments. Therefore, the
      drug effects seen here could potentially ameliorate the impairments in neuronal
      communication and cognitive processes observed in Alzheimer's disease.

PMID- 20035740
TI  - Characterization of C-terminal tail determinants involved in CRTH2 receptor
      trafficking: identification of a recycling motif.
AB  - The molecular mechanisms regulating the trafficking of the CRTH2 receptor are
      poorly understood. In the present study, we characterize C-terminal tail
      determinants involved in the agonist-induced trafficking of the CRTH2 receptor
      for prostaglandin D(2). Our results showed that progressive deletion of C
      terminal tail residues from amino acid 395 up to 337 gradually impaired CRTH2
      internalization by approximately 50% as measured by ELISA in HEK293 cells.
      Surprisingly, further deletion of the C-tail to amino acid 328 or 317 resulted in
      receptor mutants displaying internalization similar to the wild-type receptor.
      Individual mutations of Asp(330), Ser(331), Glu(332), and Leu(333) to Ala in the
      C-tail of the full length receptor resulted in a 45% increase in internalization
      of the receptor mutants relative to the wild-type receptor. Pretreatment with the
      recycling inhibitor monensin increased internalization of the wild-type receptor
      but did not affect that of the D330A, S331A, E332A and L333A mutants, indicating
      that these residues are part of a recycling motif. Further experiments revealed
      that Asp(330), Ser(331) and Glu(332) are not only involved in receptor recycling,
      but are also required for promotion of CRTH2 internalization by GRK2 and GRK5.
      Site-directed mutagenesis identified Thr(347) as a major site for PKC-induced
      internalization of the receptor. Confocal microscopy revealed that arrestin-3
      dissociated from the receptor after agonist stimulation and internalization,
      suggesting that CRTH2 is a class A G protein-coupled receptor. Our study
      identified specific amino acids in the CRTH2 receptor C-tail implicated in the
      agonist-induced internalization and the recycling of the receptor.

PMID- 20035741
TI  - Synergistic effect of [1H-[1,2,4]Oxadiazole[4,3-a]quinoxalin-1-one] and
      antidepressant drugs in the mouse forced swimming test: possible involvement of
      serotonergic pathway.
AB  - To augment the effects of classical antidepressant drugs by combination therapies
      in drug-resistant patients has been an emerging treatment strategy. In the
      present study, the potential synergistic effect of [1H-[1,2,4]Oxadiazole[4,3
      a]quinoxalin-1-one] (ODQ) and antidepressant drugs in the forced swimming test
      was evaluated. While 5mg/kg intraperitoneal administration of imipramine,
      fluoxetine or desipramine caused no effect in the duration of immobility in the
      forced swimming test (sub-effective doses), higher doses (20, 10 and 10mg/kg,
      respectively) reduced the immobility period (effective doses). When sub-effective
      doses of ODQ (15mg/kg) and imipramine (5mg/kg) were applied, there was a
      significant reduction in the immobility time compared with those of each drug
      alone. Similarly the reduction seen with the effective dose of imipramine
      (20mg/kg) was also augmented by the co-administration of ODQ (15mg/kg). By its
      sub-effective dose, ODQ exerted statistically significant augmentations in the
      responses to either sub-effective (5mg/kg) or effective dose (10mg/kg) of
      fluoxetine. By contrast, desipramine was not influenced by the co-administration
      of ODQ (15mg/kg). None of the drugs used in the present study had any effects on
      the locomotor activity test over the dose range applied. The results show that co
      administration of imipramine/fluoxetine and ODQ exhibits a supra-additive effect
      and that serotonergic rather than noradrenergic pathway may be involved in the
      synergistic effect of ODQ.

PMID- 20035742
TI  - Sex-related effects of agmatine on caffeine-induced locomotor activity in Swiss
      Webster mice.
AB  - In mammalian brain, agmatine is an endogenous amine that is synthesized through
      the decarboxylation of l-arginine by arginine decarboxylase. It has been proposed
      as a new neurotransmitter and/or neuromodulator. It was shown that agmatine had
      some beneficial effects in animal models of opioid and alcohol addiction.
      Locomotor stimulant properties of drugs such as ethanol, caffeine, nicotine and
      amphetamine have been linked to their addictive properties. The present study
      investigates the effects of agmatine on caffeine-induced locomotor activity both
      in male and female mice. Adult Swiss Webster mice were used in the study.
      Locomotor activity was measured for 30min immediately following caffeine (2.5, 5,
      10 and 20mg/kg, i.p.) or saline treatments. Agmatine (5, 10 and 20mg/kg, i.p.)
      were injected 20min before caffeine (2.5 and 5mg/kg, i.p.) administration. In
      both sexes, agmatine (5-20mg/kg) were also tested for ability to depress or
      stimulate locomotor activity in the absence of caffeine. Caffeine (5mg/kg)
      induced a significant increase in locomotor activity of both male and female
      mice. There was no significant difference in the locomotor-activating effects of
      caffeine between male and female mice. Agmatine blocked the caffeine (5mg/kg)
      induced locomotor stimulation dose dependently in male but not female mice.
      Agmatine had not any effect on the lower dose (2.5mg/kg) of caffeine in both
      sexes. These results suggest that agmatine has sex-related inhibitory effects on
      caffeine-induced locomotor activity in Swiss Webster mice, and male mice are more
      sensitive than the females to the effect of agmatine.

PMID- 20035743
TI  - Left ventricular enlargement in coxsackievirus-B3 induced chronic myocarditis-
      ongoing inflammation and an imbalance of the matrix degrading system.
AB  - Enteroviruses, especially Coxsackie B3 virus (CVB-3), cause acute viral
      myocarditis, but the detailed mechanisms leading to chronic left ventricular
      dysfunction and dilatation remain elusive. Myocardial tissues of CVB-3 infected
      and sham infected male swr/J mice were analyzed after hemodynamic evaluation on
      days 4, 7, and 28 p.i. by RT-PCR, gelatin zymography, ELISA,
      immunohistochemistry, sirius red staining, and luxol fast blue staining. In the
      early phase after infection an abnormal diastolic function was the main
      hemodynamic finding. CVB-3 infection caused impairment of left ventricular
      function combined with ventricular dilatation 7 and 28days post-infection. These
      hemodynamic findings were associated with relevant upregulation of different
      cytokines (IL-1beta, IL-6, IL-10, INF-gamma, and TNF-alpha) in the acute phase
      with persistent over-expression of IL-6, IL-10, and INF-gamma in the chronic
      phase. This virus induced myocardial inflammation was linked to a significant
      induced MMP/TIMP system (MMP-2,-3,-8, TIMP-1, uPA, tPA-mRNA expression, and MMP-2
      activity) in the acute and chronic phase leading to imbalance in the MMP/TIMP
      ratio at day 28. This imbalance in the MMP/TIMP system was significantly
      correlated to the development of ventricular dilatation. Viral persistence
      induces chronic myocardial inflammation and an imbalance of the matrix degrading
      system, associated with the development of left ventricular dysfunction and
      dilatation in chronic murine myocarditis.

PMID- 20035744
TI  - Non-opioid tolerance in juvenile and adult rats.
AB  - It has recently been shown that antinociceptive tolerance develops by repeated
      systemic administration of non-steroidal anti-inflammatory drugs (NSAIDs)
      metamizol and lysine-acetylsalicylate. This is similar to the tolerance observed
      with opioid-induced analgesia [Vanegas and Tortorici, 2002, Cell and Mol.
      Neurobiol. 22, 655-661]. In the present study, we investigated the development of
      tolerance to the analgesic effects of the additional NSAIDs analgine, ketorolac
      and xefocam in juvenile and adult rats. After injection of each drug, tail-flick
      latencies were significantly elevated on the first day followed by a progressive
      decrease in tail-flick latency (i.e., tolerance) over the 5-day period, as well
      as cross-tolerance to morphine-induced analgesia. Tolerance to the analgesic
      effect of all three NSAIDs developed more rapidly in juvenile compared to adult
      rats. Pretreatment with naloxone completely prevented the analgesic effects of
      these drugs in tail-flick and hot plate tests for both juvenile and adult rats.
      Moreover, each NSAID exhibited cross-tolerance when tolerance to morphine had
      been induced by systemic morphine delivered repeatedly over 5-day period in both
      age groups. Our data confirm other recent findings that tolerance to the
      analgesic action of NSAIDs may depend on an opiate-mediated mechanism.

PMID- 20035745
TI  - Inhibition of endogenous hydrogen sulfide synthesis by PAG protects against
      ethanol-induced gastric damage in the rat.
AB  - Hydrogen sulfide (H(2)S) is a gaseous mediator involved in a multitude of
      physiological functions; however the role of H(2)S in the gut is far from being
      understood completely. The aim of this study was to determine the effect of d-l
      propargylglycine (PAG), an inhibitor of H(2)S synthesis, on ethanol-induced
      gastric injury in rat and to examine the role of l-cysteine, exogenous H(2)S,
      prostaglandins, non-protein sulphydryls groups, nitric oxide and K(ATP) channels
      in the gastroprotective effect of PAG. Administration of PAG (3.12 to 75mg/kg
      i.p.) or l-cysteine (0.3 to 300mg/kg, p.o.) exhibited a dose-dependent protective
      effect after intragastric administration of 1ml of ethanol to induce gastric
      injury. The gastroprotective effect of PAG (25mg/kg i.p.) was maintained after
      post-treatment with l-cysteine (10mg/kg p.o.), while NaHS (8.4mg/kg p.o.)
      inhibited this effect. The levels of gastric hydrogen sulfide were increased
      after ethanol-induced gastric damage and they were reverted by PAG while
      prostaglandin E(2) levels in gastric tissue were decreased by ethanol and PAG did
      not revert to this effect. Pretreatment with indomethacin (10mg/kg i.p.) and N
      ethylmaleimide (NEM, 10mg/kg s.c.) resulted in a reversion of the
      gastroprotective effect of PAG while N(G)-nitro-l-arginine methyl ester (L-NAME,
      70mg/kg s.c.), glibenclamide (1mg/kg i.p.) or diazoxide (3mg/kg i.p.) did not
      induce any changes. These results suggest that ethanol-induced gastric injury is
      related with an increment of endogenous H(2)S levels, and therefore a decrement
      of H(2)S levels by PAG is a benefit to protect gastric injury caused by ethanol.

PMID- 20035746
TI  - Essential role of nitric oxide in sepsis-induced impairment of endothelium
      derived hyperpolarizing factor-mediated relaxation in rat pulmonary artery.
AB  - Both endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor
      (EDHF) are important vasodilators in pulmonary circulation. Sepsis is known to
      impair endothelium-dependent dilation in the pulmonary vasculature, but the
      mechanisms are incompletely understood. We have examined the relative
      contribution of EDHF/NO to the attenuated endothelium-dependent relaxation of
      pulmonary artery in sepsis, and the role of inducible nitric oxide synthase
      (iNOS)-derived NO in this mechanism. Sepsis was induced in male adult Wistar rats
      by caecal ligation and puncture. At 18h after surgery, left and right branches of
      pulmonary arteries were isolated for tension recording, NO/cyclic guanosine
      monophosphate (cGMP) measurements, mRNA and protein expressions. Despite a marked
      decrease in the arterial endothelial nitric oxide synthase (eNOS) mRNA and
      phosphorylated-eNOS (p-eNOS) protein expressions in sepsis, endothelium-dependent
      relaxation to acetylcholine (ACh) mediated by NO, acetylcholine-stimulated NO
      release and tissue cGMP levels were moderately inhibited. Sepsis however
      abolished the N(G)-Nitro-l-arginine methyl ester (L-NAME)/indomethacin-resistant
      arterial relaxation (EDHF response) to acetylcholine in this vessel. In vitro
      treatment of the arterial rings from septic rats with 1400W, a selective
      inhibitor of iNOS restored the EDHF response, but had no effect on the
      acetylcholine-induced relaxation mediated by endothelial NO. The functional role
      of iNOS-derived NO in impairing EDHF-mediated relaxation was coincident with an
      increased basal NO production, iNOS mRNA and protein expressions in the rat
      pulmonary artery. In conclusion, the loss of the EDHF response may be primarily
      responsible for the endothelial dysfunction in sepsis, and its restoration by a
      selective iNOS inhibitor may improve pulmonary vasodilation.

PMID- 20035747
TI  - Protective effects of the free radical scavenger edaravone on acute pancreatitis
      associated lung injury.
AB  - Impaired lung function is the primary contributor to most deaths associated with
      severe acute pancreatitis. It is widely accepted that oxidative stress plays a
      central role in the pathogenesis of pancreatitis and associated complications.
      Therefore, in the present study, we investigated whether therapeutic treatment
      with the free radical scavenger edaravone could protect rats against acute
      pancreatitis and the associated lung injury. Acute pancreatitis was induced by
      infusion of 1ml/kg of sodium taurocholate (3% solution) into the biliopancreatic
      duct. Edaravone (8mg/kg) was administered 1h and 13h after inducing pancreatitis,
      the severity of pancreatic and pulmonary injuries was evaluated 24h after
      inducing pancreatitis. Edaravone treatment significantly reduced the elevated
      malondialdehyde levels in rat lungs after acute pancreatitis, suggesting an
      important role for free radicals in acute pancreatitis-associated lung injury. In
      addition, edaravone showed significant protective effects against neutrophil
      infiltration and tissue injury in both pancreas and lung, as demonstrated by
      serum amylase levels, myeloperoxidase activity and histopathological analysis.
      Edaravone treatment also attenuated the elevated mRNA levels of pro-inflammatory
      cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in rat
      lungs after acute pancreatitis. In conclusion, edaravone protects rats against
      acute pancreatitis-associated lung injury, probably through its antioxidant and
      anti-inflammatory effects. Thus, edaravone shows promise as a treatment for lung
      injury in patients with acute pancreatitis.

PMID- 20035748
TI  - Claudin expression in the bone-lining cells of female rats exposed to long
      standing acidemia.
AB  - Besides enhancing osteoclast-mediated bone resorption, chronic metabolic acidosis
      (CMA) induces mineral efflux across the epithelial-like bone membrane formed by
      bone-lining cells (inactive osteoblasts), possibly via the paracellular pathway.
      However, there was a compensatory mechanism that restricted bone loss in the late
      phase of CMA, and changes in the expression of claudins, which are tight junction
      proteins known to regulate epithelial barrier function, were therefore
      anticipated in bone-lining cells. Herein, primary rat osteoblasts were found to
      express several transcripts of claudins, i.e., claudin-5, -11, -14, -15 and -16.
      Their protein expressions in bone-lining cells were demonstrated by
      immunohistochemistry in decalcified tibial sections. After exposure to CMA
      induced by oral administration of 1.5% NH(4)Cl for 21 days, expression of claudin
      14, which normally seals the paracellular space and restricts ion movement, was
      increased, whereas that of claudin-15 and -16 which form pores for ion transport
      were decreased. Expressions of claudin-5 and -11 were not changed by CMA. In
      conclusion, the bone-lining cells of rats exposed to CMA for 21 days upregulated
      an ion-restrictive claudin (i.e., claudin-14), while downregulating ion-permeable
      claudins (i.e., claudin-15 and -16). These cellular responses might be parts of a
      compensatory mechanism accounting for deceleration of bone loss in late CMA.

PMID- 20035749
TI  - Time dependent subthalamic local field potential changes after DBS surgery in
      Parkinson's disease.
AB  - Local field potentials (LFPs) recorded through electrodes implanted in patients
      with Parkinson's disease (PD) for deep brain stimulation (DBS) provided
      physiological information about the human basal ganglia. However, LFPs were
      always recorded 2-7 days after electrode implantation ("acute" condition).
      Because changes in the tissue surrounding the electrode occur after DBS surgery
      and could be relevant for LFPs, in this work we assessed whether impedance and
      LFP pattern are a function of the time interval between the electrode implant and
      the recordings. LFPs and impedances were recorded from 11 patients with PD
      immediately after (T-0h), 2 h after (T-2h), 2 days after (T-48h), and 1 month
      after (T-30d, "chronic" condition) surgery. Impedances at T-0h were significantly
      higher than at all the other time intervals (T-2h, p=0.0005; T-48h, p=0.0002; T
      30d, p=0.003). Correlated with this change (p=0.005), the low-frequency band (2-7
      Hz) decreased at all time intervals (p=0.0005). Conversely, the low- (8-20 Hz)
      and the high-beta (21-35 Hz) bands increased in time (low-beta, p=0.003; high
      beta, p=0.022), but did not change between T-48h and T-30d. Our results suggest
      that DBS electrode impedance and LFP pattern are a function of the time interval
      between electrode implant and LFP recordings. Impedance decrease could be related
      to changes in the electrode/tissue interface and in the low-frequency band.
      Conversely, beta band modulations could raise from the adaptation of the neural
      circuit. These findings confirm that results from LFP analysis in the acute
      condition can be extended to the chronic condition and that LFPs can be used in
      novel closed-loop DBS systems.

PMID- 20035750
TI  - A Georgian woman with dysphagia and stridor.

PMID- 20035751
TI  - Drug target identification, validation, characterisation and exploitation for
      treatment of Acanthamoeba (species) infections.
AB  - New more efficacious antimicrobials as required for the treatment of Acanthamoeba
      infections as those currently available require arduous treatment regimes, are
      not always effective and are poorly active against the cystic stages. Herein, we
      review potential drug targets including tubulin, alternative oxidase, amino acid
      biosynthesis and myosin. In addition, we review the literature for current
      missing tools and resources for the identification, validation and development of
      new antimicrobials for this organism. Additional targets should come to light
      through a concerted genome sequencing effort.

PMID- 20035752
TI  - The PsbS protein controls the macro-organisation of photosystem II complexes in
      the grana membranes of higher plant chloroplasts.
AB  - The PsbS protein is a critical component in the regulation of non-photochemical
      quenching (NPQ) in higher plant photosynthesis. Electron microscopy and image
      analysis of grana membrane fragments from wild type and mutant Arabidopsis plants
      showed that the semi-crystalline domains of photosystem II supercomplexes were
      identical in the presence and absence of PsbS. However, the frequency of the
      domains containing crystalline arrays was increased in the absence of PsbS.
      Conversely, there was a complete absence of such arrays in the membranes of
      plants containing elevated amounts of this protein. It is proposed that PsbS
      controls the macro-organisation of the grana membrane, providing an explanation
      of its role in NPQ.

PMID- 20035754
TI  - Biochemistry and physiology of mitochondrial ion channels involved in
      cardioprotection.
AB  - Over the past decades there has been considerable progress in understanding the
      multifunctional roles of mitochondrial ion channels in metabolism, energy
      transduction, ion transport, signaling, and cell death. Recent data have
      suggested that some of these channels function under physiological condition, and
      others may be activated in response to pathological insults and play a key role
      in cytoprotection. This review outlines our current understanding of the
      molecular identity and pathophysiological roles of the mitochondrial ion channels
      in the heart with particular emphasis on cardioprotection against
      ischemia/reperfusion injury, and future research on mitochondrial ion channels.

PMID- 20035753
TI  - Autophagy and tumorigenesis.
AB  - Autophagy, or cellular self-digestion, is activated in cancer cells in response
      to multiple stresses and has been demonstrated to promote tumor cell survival and
      drug resistance. Nonetheless, genetic evidence supports that autophagy functions
      as a tumor suppressor mechanism. Hence, the precise role of autophagy during
      cancer progression and treatment is both tissue and context dependent. Here, we
      discuss our current understanding of the biological functions of autophagy during
      cancer development, overview how autophagy is regulated by cancer-associated
      signaling pathways, and review how autophagy inhibition is being exploited to
      improve clinical outcomes.

PMID- 20035755
TI  - Very long chain sphingolipids: tissue expression, function and synthesis.
AB  - Forecort membranes of all mammalian cells contain, in addition to
      phosphoglycerolipids and cholesterol, substantial amounts of sphingolipids. In
      most cells the acyl moieties of these sphingolipids are of long chain type (C16
      24) and often saturated. However, epidermal keratinocytes and male germ cells
      largely express sphingolipids with very long chain-acyl moieties (C26-C36) during
      their differentiation and maturation. This expression seems to depend on CerS3,
      one of six ceramide synthases. However, the complex biosynthetic sequence for
      both epidermal and testicular sphingolipids has not been elucidated completely.
      Whereas it is established that omega-hydroxylated very long chain-sphingolipids
      are essential for proper skin barrier function, the role of polyunsaturated very
      long chain-sphingolipids (ceramides, sphingomyelins and glycosphingolipids) in
      differentiating spermatocytes/spermatids is just beginning to be revealed.

PMID- 20035756
TI  - Properties of the intracellular transient receptor potential (TRP) channel in
      yeast, Yvc1.
AB  - Transient receptor potential (TRP) channels are found among mammals, flies,
      worms, ciliates, Chlamydomonas, and yeast but are absent in plants. These
      channels are believed to be tetramers of proteins containing six transmembrane
      domains (TMs). Their primary structures are diverse with sequence similarities
      only in some short amino acid sequence motifs mainly within sequences covering
      TM5, TM6, and adjacent domains. In the yeast genome, there is one gene encoding a
      TRP-like sequence. This protein forms an ion channel in the vacuolar membrane and
      is therefore called Yvc1 for yeast vacuolar conductance 1. In the following we
      summarize its prominent features.

PMID- 20035757
TI  - Expression and localization of stanniocalcin 1 in swine ovary.
AB  - Stanniocalcin 1 (STC 1) is a glycoprotein involved in mineral homeostasis and was
      first identified in fish. Its mammalian homologue has been implicated in the
      regulation of various biological processes, including angiogenesis and
      steroidogenesis both of which are fundamental events in ovarian function.
      Interestingly, the highest level of STC 1 expression in mammals occurs in ovarian
      tissue but no information is available on swine species. Therefore, the present
      study was undertaken to investigate the expression and the immunolocalization of
      STC 1 in swine ovary. In addition, we evaluated whether swine granulosa cells
      synthesize STC 1 and its possible modulation by hypoxia, a physiological
      condition in ovarian follicle growth. Our data show STC 1 for the first time in
      swine ovary; moreover, we demonstrate STC 1 production by granulosa cells, both
      in basal condition and in response to oxygen deprivation. The latter is
      suggestive of a potential modulatory role for STC 1 in hypoxia-driven
      angiogenesis.

PMID- 20035758
TI  - Triple chimeric islet autoantigen IA2-ZnT8WR to facilitate islet autoantibody
      determination.
AB  - Type 1A diabetes is strongly associated with the presence of islet
      autoantibodies. Large scale population screening of islet autoantibodies is
      essential for many different national and international studies related to
      defining subtypes of diabetes, the natural history of the disease, and for trials
      of prevention. Testing for relevant autoantibodies has become more difficult as
      the number of important autoantibodies/epitopes increases. In the present study,
      we created a chimeric protein, IA2-ZnT8WR, with two major islet autoantigens, IA
      2 and the recent Zinc transporter 8 (ZnT8). The chimeric molecule included both
      common polymorphisms of the ZnT8 molecule, arginine or tryptophan at position
      325. Serum samples from 284 patients with newly diagnosed diabetes, 10
      prediabetics, and 110 age-matched normal controls were analyzed for islet
      autoantibodies reacting with the IA2-ZnT8WR molecule. Autoantibodies to the
      chimeric molecule were compared to reactivity with individual assays detecting
      autoantibodies reacting with the separate molecules (IA-2, ZnT8-R and ZnT8-W).
      With this chimeric protein antigen, IA2-ZnT8WR, one radioassay is able to detect
      autoantibodies to IA-2 and to both major forms of ZnT8 (100% sensitivity, 100%
      unchanged specificity, relative to individual molecules). The chimeric assay
      provides an efficient and economical technique to screen for islet autoantibodies
      reacting with IA-2 and ZnT8.

PMID- 20035759
TI  - Protein quantification by chemiluminescent Western blotting: elimination of the
      antibody factor by dilution series and calibration curve.
AB  - Quantification of chemiluminescent signals from a Western blot is routinely used
      to determine the increase or the decrease in protein expression or modification
      in cell or tissue extracts. However, although scientists readily agree that such
      a procedure is not quantitative, it is nonetheless used quantitatively in most
      publications without appropriate controls that would increase the accuracy of the
      measurement. Here we reexamined this aspect and found that the primary antibody
      itself influences the relation between the Western blot signal and the protein
      amount on the membrane. This relation is non-linear and varies from one antibody
      to another. In that context, we strongly encourage researchers to use dilution
      series and calibration curve when quantifying protein by Western blot using
      chemiluminescent signal.

PMID- 20035760
TI  - A validated assay to measure soluble IL-7 receptor shows minimal impact of IL-7
      treatment.
AB  - IL-7 is a crucial cytokine for T cell hematopoiesis and peripheral homeostasis
      which by signaling through its receptor alpha chain (CD127) is essential for
      inducing T cell proliferation and survival. Since the specific CD127 alpha chain
      is found in a soluble state (sCD127) and at a high level in plasma (ng/mL), it is
      important to develop a sensitive and reliable assay in order to investigate the
      potential role of this receptor in the regulation of IL-7 physiologic,
      physipathologic and therapeutic effects. We here report a fully validated method
      to measure sCD127 in human and simian plasma using a method based on ELISA MSD
      technology. We demonstrate that sCD127 is detectable at various levels in the
      plasma of healthy humans as well as in that of healthy Rhesus and Cynomolgus
      macaques (106.72, 205.26 and 366.95 ng/mL respectively). Moreover, as opposed to
      the sCD25/IL-2 tandem, we demonstrate that IL-7 treatment has no impact on sCD127
      plasma concentration in patients infected by HIV.

PMID- 20035761
TI  - Mercuric mercaptide of penicillenic acid, a novel hapten for relevant
      immunoassay, synthesized from penicillin.
AB  - The synthesis of mercuric mercaptide of penicillenic acid (MMPA) has been the
      basis for detection of penicillin for nearly 40 years (J. Pharm. Pharmacol.,
      1972, 24, 790; Chinese Pharmacopoeia Ed. II, 1995). Herein, experiments were
      performed on: (1) synthesis of MMPA used as a novel mercuric hapten, (2)
      preparation of mercuric antigen of MMPA-BSA, (3) production of antibodies by
      rabbits immunized with the antigen, and (4) properties of the antibodies studied
      by ELISA. The results show that: (1) the antigen is safe for immunized animals;
      (2) high titer antibodies against MMPA are obtained implying good immunogenicity
      of the antigen; (3) antisera show slightly higher affinity to OVA-GHS-HgCl than
      OVA-GSH, indicating weak specific affinity of antisera against mercuric ion. Even
      the weak specific affinity, the hapten and its antigen have potential uses in
      immunoassays of mercuric ion in environment and food samples, because of easy
      chemical selective conversion from mercuric ion to MMPA and complete
      decomposition of un-reacted penicillin in acidic solution.

PMID- 20035762
TI  - Antisera-mediated in vivo reduction of Cry1Ac toxicity in Helicoverpa armigera.
AB  - A functional assessment of Bacillus thuringiensis (Bt) toxin receptors in the
      midgut of lepidopteran insects will facilitate understanding of the toxin mode of
      action and provide effective strategies to counter the development of resistance.
      In this study, we produced anti-aminopeptidase (APN) and anti-cadherin sera with
      purified Cry1Ac toxin-binding APN or cadherin fragments from Heliocoverpa
      armigera. Antisera were evaluated for their effects on Cry1Ac toxicity through
      bioassays. Our results indicated that both the anti-APN and anti-cadherin sera
      reduced Cry1Ac toxicity in vivo, although cadherin antiserum reduced toxicity
      more than APN antiserum. These results suggest that both APN and cadherin are
      involved in Cry1Ac intoxication of H. armigera, evidence that the pore formation
      model may be representative of Cry1Ac toxin mode of action in this insect.

PMID- 20035763
TI  - Thermoregulation in mixed-species colonies of honeybees (Apis cerana and Apis
      mellifera).
AB  - Apis cerana and Apis mellifera normally display different strategies in cooling
      hive temperature, raising the question whether they would coordinate their
      efforts in to achieve stable thermoregulation in mixed colonies. The results show
      that the normal temperatures in the brood area in mixed colonies are more similar
      to those of pure A. cerana colonies than pure A. mellifera colonies. Under heat
      stress, A. cerana workers are more sensitive, and initiate fanning earlier than
      A. mellifera workers. In mixed colonies, the former become the main force for
      thermoregulation. When worker bees of both species were fanning together at the
      entrance, their own species-specific postures were adopted, but due to a
      significantly smaller number of A. mellifera workers engaged in fanning, the
      cooling efficiency of mixed colonies were closest to that of pure A. cerana
      colonies.

PMID- 20035764
TI  - Subcellular fractionation of midgut cells of the sunn pest Eurygaster integriceps
      (Hemiptera: Scutelleridae): enzyme markers of microvillar and perimicrovillar
      membranes.
AB  - The subcellular distributions of six digestive and non-digestive enzymes (alpha
      glucosidase, beta-glucosidase, alkaline phosphatase, acid phosphatase,
      aminopeptidase and lactate dehydrogenase) of Eurygaster integriceps have been
      studied. The subcellular distributions of acid phosphatase and alpha-glucosidase
      are similar and the gradient ultracentrifugation profiles of these two enzymes
      overlap. Two partially membrane-bound enzymes, alkaline phosphatase and beta
      glucosidase have similar distributions in differential centrifugation fractions,
      which are different from that of alpha-glucosidase. Sucrose gradient
      ultracentrifugation of membranes from luminal contents showed that beta
      glucosidase carrying membranes are heavier. SDS-polyacrylamide gel
      electrophoresis (SDS-PAGE) revealed that the profile of proteins extracted from
      beta-glucosidase carrying membranes is different from that of alpha-glucosidase
      carrying membranes. We conclude that beta-glucosidase and aminopeptidase are
      markers of microvillar membrane (MM) and perimicrovillar space, respectively,
      while alpha-glucosidase and acid phosphatase are perimicrovillar markers. In E.
      integriceps V1 luminal content is a rich source of PMM and MM and that is used to
      resolve these membranes.

PMID- 20035765
TI  - Resistance to Brown Ring Disease in the Manila clam, Ruditapes philippinarum: a
      study of selected stocks showing a recovery process by shell repair.
AB  - European stocks of the Manila clam Ruditapes philippinarum are affected by the
      Brown Ring Disease (BRD), which is caused by Vibrio tapetis. BRD is characterized
      by an accumulation of a brown organic matrix on the inner face of the shell.
      Clams that recover from BRD develop a white mineralized layer covering the brown
      matrix. Stocks of clams that showed resistance to BRD development, as enhanced
      recovery, have been monitored since 2000. We have examined two selected stocks: a
      Low Susceptibility (LS) stock and a High Susceptibility stock (HS), over three
      generations. The LS stock showed less evidence of the BRD symptoms, and more
      evidence of total shell repair, both in the field and following experimental
      challenge with V. tapetis, indicating that some clams may be less vulnerable to a
      V. tapetis attack than others. The inner face of the valves of the LS and HS
      clams of the two last generations were analysed with scanning electron
      microscopy. Examination of shells from BRD-affected clams showed that during the
      repair process, calcium crystals were progressively laid down until the affected
      zone was entirely covered. By the end of the shell repair process, a final
      organic layer covered the calcium crystal mounds. This layer seemed essential in
      the recovery process. The results indicate that the shell repair capability of
      the clams is the principal mechanism implicated in the development of BRD
      resistance in the Manila clam stocks. However, this resistance did not increase
      with generation because the broodstock was maintained at a site where selection
      pressure was low, due to a low prevalence of V. tapetis.

PMID- 20035766
TI  - Interactions between Bacillus thuringiensis subsp. kurstaki HD-1 and midgut
      bacteria in larvae of gypsy moth and spruce budworm.
AB  - We examined interaction between Bacillus thuringiensis subsp. kurstaki HD-1
      (Foray 48B) and larval midgut bacteria in two lepidopteran hosts, Lymantria
      dispar and Choristoneura fumiferana. The pathogen multiplied in either moribund
      (C. fumiferana) or dead (L. dispar) larvae, regardless of the presence of midgut
      bacteria. Inoculation of L. dispar resulted in a pronounced proliferation of
      enteric bacteria, which did not contribute to larval death because B.
      thuringiensis was able to kill larvae in absence of midgut bacteria. Sterile,
      aureomycin- or ampicillin-treated larvae were killed in a dose-dependent manner
      but there was no mortality among larvae treated with the antibiotic cocktail used
      by Broderick et al. (2006, 2009). These results do not support an obligate role
      of midgut bacteria in insecticidal activity of HD-1. The outcome of experiments
      on the role of midgut bacteria may be more dependent on which bacterial species
      are dominant at the time of experimentation than on host species per se. The L.
      dispar cohorts used in our study had a microflora, that was dominated by
      Enterococcus and Staphylococcus and lacked Enterobacter. Another factor that can
      confound experimental results is the disk-feeding method for inoculation, which
      biases mortality estimates towards the least susceptible portion of the test
      population.

PMID- 20035767
TI  - Pervasive associations between Cybaeus spiders and the bacterial symbiont
      Cardinium.
AB  - Cardinium is a recently discovered maternally transmitted bacterial endosymbiont
      in the Bacteroidetes that has thus far been documented in five arthropod orders.
      While its effects on his hosts are largely unknown, a few strains have been shown
      to manipulate host reproduction in parasitic wasps and in mites, either by
      transforming males into females, or by causing mating incompatibilities between
      infected males and uninfected males. Cardinium has recently been reported to be
      widespread in spiders, and in this study, we document pervasive infections in
      Cybaeus spiders, which are some of the most abundant yet understudied spiders in
      the understory of moist Western North American forests. 12/20 species, as well as
      96% of individuals in a local population of Cybaeus signifer were infected.
      Phylogenetic analysis revealed three closely related symbiont haplotypes within
      Cybaeus. Haplotypes clustered within geographically close species, suggesting
      that horizontal transmission might be quite high in this symbiont lineage.

PMID- 20035768
TI  - Prediction of the parallel/antiparallel orientation of beta-strands using amino
      acid pairing preferences and support vector machines.
AB  - In principle, structural information of protein sequences with no detectable
      homology to a protein of known structure could be obtained by predicting the
      arrangement of their secondary structural elements. Although some ab initio
      methods for protein structure prediction have been reported, the long-range
      interactions required to accurately predict tertiary structures of beta-sheet
      containing proteins are still difficult to simulate. To remedy this problem and
      facilitate de novo prediction of beta-sheet containing protein structures, we
      developed a support vector machine (SVM) approach that classified parallel and
      antiparallel orientation of beta-strands by using the information of interstrand
      amino acid pairing preferences. Based on a second-order statistics on the
      relative frequencies of each possible interstrand amino acid pair, we defined an
      average amino acid pairing encoding matrix (APEM) for encoding beta-strands as
      input in the prediction model. As a result, a prediction accuracy of 86.89% and a
      Matthew's correlation coefficient value of 0.71 have been achieved through 7-fold
      cross-validation on a non-redundant protein dataset from PISCES. Although several
      issues still remain to be studied, the method presented here to some extent could
      indicate the important contribution of the amino acid pairs to the beta-strand
      orientation, and provide a possible way to further be combined with other
      algorithms making a full 'identification' of beta-strands.

PMID- 20035769
TI  - Nicotine improves ethanol-induced memory impairment: the role of dorsal
      hippocampal NMDA receptors.
AB  - AIMS: The current study was undertaken to determine the role of dorsal
      hippocampal N-methyl-d-aspartate (NMDA) receptors in nicotine's effect on
      impairment of memory by ethanol. MAIN METHODS: Adult male mice were cannulated in
      the CA1 regions of dorsal hippocampi and trained on a passive avoidance learning
      task for memory assessment. KEY FINDINGS: We found that pre-training
      intraperitoneal (i.p.) administration of ethanol (0.5 and 1g/kg) decreased memory
      retrieval when tested 24h later. Pre-test administration of ethanol reversed the
      decrease in inhibitory avoidance response induced by pre-training ethanol.
      Similar to ethanol, pre-test administration of nicotine (0.125-0.75 mg/kg, s.c.)
      prevented impairment of memory by pre-training ethanol. In the animals that
      received ethanol (1g/kg, i.p) before training and tested following intra-CA1
      administration of different doses of NMDA (0.0005-0.005 microg/mouse), no
      significant change was observed in the retrieval latencies. Co-administration of
      the same doses of NMDA with an ineffective dose of nicotine (0.125 mg/kg, s.c.)
      significantly improved the memory retrieval and mimicked the effects of pre-test
      administration of a higher dose of nicotine. Pre-test intra-CA1 microinjection of
      MK-801 (0.25-1 microg/mouse), which had no effect alone, in combination with an
      effective dose of nicotine (0.75 mg/kg, s.c.) prevented the improving effect of
      nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1
      microinjection of MK-801 reversed the NMDA-induced potentiation of the nicotine
      response. SIGNIFICANCE: The results suggest the importance of NMDA glutamate
      system(s) in the CA1 regions of dorsal hippocampus for improving the effect of
      nicotine on the ethanol-induced amnesia.

PMID- 20035770
TI  - Prostaglandin E2 upregulates survivin expression via the EP1 receptor in
      hepatocellular carcinoma cells.
AB  - AIMS: Cyclooxygenase-2 (COX-2)-controlled production of prostaglandin E(2)
      (PGE(2)) has been implicated in cell growth and metastasis in many cancers.
      Recent studies have found that COX-2 is co-expressed with survivin in many
      cancers. Survivin is a member of the inhibitor-of-apoptosis protein family. Some
      COX-2 inhibitors (e.g., celecoxib) can reduce the expression of survivin.
      However, little is known about the mechanism of PGE(2)-mediated expression of
      survivin. This study was designed to uncover the effect of PGE(2) on survivin
      expression in hepatocellular carcinoma cells. MAIN METHODS: The effects of PGE(2)
      and EP1 agonist on survivin expression were examined in HUH-7 and HepG2 cells.
      Plasmid transfection and EP1 siRNA were used to regulate the expression of COX-2
      and the EP1 receptor protein. KEY FINDINGS: PGE(2) treatment increased survivin
      expression 2.3-fold. COX-2 overexpression resulted in a similar level of survivin
      upregulation. However, this effect was suppressed by treatment with celecoxib.
      EP1 receptor transfection or treatment with a selective EP1 agonist mimicked the
      effect of PGE(2) treatment. Conversely, the PGE(2)-induced upregulation of
      survivin was blocked by treatment with a selective EP1 antagonist or siRNA
      against the EP1 receptor. The phosphorylation of EGFR and Akt were elevated in
      EP1 agonist-treated cells, and both EGFR and PI3K inhibitors suppressed the
      upregulation of survivin induced by PGE(2) or EP1 agonist. SIGNIFICANCE: PGE(2)
      regulates survivin expression in hepatocellular carcinoma cells through the EP1
      receptor by activating the EGFR/PI3K pathway. Targeting the PGE(2)/EP1/survivin
      signaling pathway may aid the development of new therapeutic strategies for both
      the prevention and treatment of this cancer.

PMID- 20035771
TI  - Unsuitability of lymphoblastoid cell lines as surrogate of cryopreserved isolated
      lymphocytes for the analysis of DNA double-strand break repair activity.
AB  - As first task of a comprehensive investigation on DNA repair genotype-phenotype
      correlations, the suitability of Epstein-Barr virus (EBV)-transformed
      lymphoblastoid cell lines (LCLs) as surrogate of cryopreserved peripheral blood
      mononuclear cells (PBMCs) in DNA repair phenotypic assays was evaluated. To this
      aim the amount of DNA damage induced by gamma-rays and DNA repair capacity were
      evaluated in unstimulated (G(0)) and mitogen-simulated (G(2)) PBMC from 20
      healthy subjects and in EBV-transformed LCL obtained from the same individuals.
      Phosphorylation of histone H2AX, micronuclei and chromosomal aberrations were the
      end-points investigated. The results obtained show higher basal frequencies of
      binucleated cells bearing micronuclei and nucleoplasmic bridge (NPB) in LCL with
      respect to PBMC, suggesting that EBV transformation may be associated with
      chromosomal instability. After irradiation, higher levels of micronuclei were
      induced in G(0)-treated PBMC compared to cycling LCL; conversely, NPB were more
      frequent in LCL than in PBMC. Moreover, higher levels of chromosomal aberrations
      were observed in G(2)-treated PBMC compared to LCL. Concerning gamma-H2AX
      measurements, phosphorylation levels 1h after treatment and dephosphorylation
      kinetics were basically similar in LCL and in PBMC. However, while Spearman's
      test showed a strong correlation between the results obtained in replicated
      experiments with PBMC, high inter-experimental variability and poor
      reproducibility was observed in the experiments performed with LCL, possibly due
      to the intrinsic instability of LCL. In summary, both the analysis of gamma-H2AX
      and the evaluation of chromosome damage highlighted a larger inter-experimental
      variability in the results obtained with LCL compared to PBMC. Noteworthy, the
      two set of results proved to lack any significant correlation at the individual
      level. These results indicate that LCL may be unsuitable for investigating
      genotype-phenotype correlations with phenotypic DNA repair assays, especially
      when low impact functional genetic variants are involved.

PMID- 20035772
TI  - Cilostazol improves cognitive function in mice by increasing the production of
      insulin-like growth factor-I in the hippocampus.
AB  - Insulin-like growth factor I (IGF-I) exerts beneficial effects on cognitive
      function by inducing angiogenesis and neurogenesis in the hippocampus. We
      demonstrated that stimulation of sensory neurons in the gastrointestinal tract
      increased IGF-I production in the hippocampus, and thereby improved cognitive
      function in mice. Since cAMP plays a critical role in stimulation of sensory
      neurons, the type III phosphodiesterase (PDE3) inhibitor cilostazol might
      increase IGF-I production in the hippocampus by stimulating sensory neurons and
      thus improve cognitive function in mice. We tested this hypothesis in the present
      study. Cilostazol increased the release of calcitonin gene-related peptide (CGRP)
      and levels of cAMP in dorsal root ganglion (DRG) neurons isolated from wild-type
      (WT) mice. Tissue levels of cAMP in the DRG and hippocampus and those of CGRP,
      IGF-I, and IGF-I mRNA in the hippocampus were increased after 4-week oral
      administration of cilostazol to WT mice. Levels of expression of c-fos in the
      spinal dorsal horns, parabrachial nuclei, the solitary tract nucleus, and the
      hippocampus were also increased in these animals. Significant enhancement of
      angiogenesis and neurogenesis was observed in the dentate gyrus of the
      hippocampus after cilostazol administration in WT mice. Significant improvement
      of spatial learning was also observed in WT mice administered cilostazol.
      However, none of these effects in WT mice were observed in CGRP-knockout mice.
      These observations suggest that cilostazol may improve cognitive function in mice
      by increasing the hippocampal production of IGF-I through stimulation of sensory
      neurons.

PMID- 20035774
TI  - Chronic stress enhances synaptic plasticity due to disinhibition in the anterior
      cingulate cortex and induces hyper-locomotion in mice.
AB  - The anterior cingulate cortex (ACC) is involved in the pathophysiology of a
      variety of mental disorders, many of which are exacerbated by stress. There are
      few studies, however, of stress-induced modification of synaptic function in the
      ACC that is relevant to emotional behavior. We investigated the effects of
      chronic restraint stress (CRS) on behavior and synaptic function in layers II/III
      of the ACC in mice. The duration of field excitatory postsynaptic potentials
      (fEPSPs) was longer in CRS mice than in control mice. The frequency of miniature
      inhibitory postsynaptic currents (mIPSCs) recorded by whole-cell patch-clamping
      was reduced in CRS mice, while miniature excitatory postsynaptic currents
      (mEPSCs) remained unchanged. Paired-pulse ratios (PPRs) of the fEPSP and evoked
      EPSC were larger in CRS. There was no difference in NMDA component of evoked
      EPSCs between the groups. Both long-term potentiation (LTP) and long-term
      depression of fEPSP were larger in CRS mice than in control mice. The differences
      between the groups in fEPSP duration, PPRs and LTP level were not observed when
      the GABA(A) receptor was blocked by bicuculline. Compared to control mice, CRS
      mice exhibited hyper-locomotive activity in an open field test, while no
      difference was observed between the groups in anxiety-like behavior in a
      light/dark choice test. CRS mice displayed decreased freezing behavior in fear
      conditioning tests compared to control mice. These findings suggest that CRS
      facilitates synaptic plasticity in the ACC via increased excitability due to
      disinhibition of GABA(A) receptor signalling, which may underlie induction of
      behavioral hyper-locomotive activity after CRS.

PMID- 20035775
TI  - Approachability in Williams syndrome.

PMID- 20035773
TI  - Cannabinoid receptor-mediated antinociception with acetaminophen drug
      combinations in rats with neuropathic spinal cord injury pain.
AB  - Pre-clinical evidence demonstrates that neuropathic spinal cord injury (SCI) pain
      is maintained by a number of neurobiological mechanisms, suggesting that
      treatments directed at several pain-related targets may be more advantageous
      compared to a treatment focused on a single target. The current study evaluated
      the efficacy of the non-opiate analgesic acetaminophen, which has several
      putative analgesic mechanisms, combined with analgesic drugs used to treat
      neuropathic pain in a rat model of below-level neuropathic SCI pain. Following an
      acute compression of the mid-thoracic spinal cord, rats exhibited robust hind paw
      hypersensitivity to innocuous mechanical stimulation. Fifty percent
      antinociceptive doses of gabapentin, morphine, tramadol or memantine were
      combined with an ineffective dose of acetaminophen; acetaminophen alone was not
      antinociceptive. The combination of acetaminophen with either tramadol or
      memantine resulted in an additive antinociceptive effect. Acetaminophen combined
      with either morphine or gabapentin, however, resulted in supra-additive
      (synergistic) efficacy. One of the analgesic mechanisms of acetaminophen is
      inhibiting the uptake of endocannabinoids from the extracellular space. Pre
      treatment with AM251, a cannabinoid-1 receptor (CB1) antagonist, significantly
      diminished the antinociceptive effect of the acetaminophen + gabapentin
      combination. Pre-treatment with AM630, a cannabinoid-2 receptor (CB2) antagonist,
      did not have an effect on this combination. By contrast, both AM251 and AM630
      reduced the efficacy of the acetaminophen + morphine combination. None of the
      active drugs alone were affected by either CB receptor antagonist. The results
      imply that modulation of the endocannabinoid system in addition to other
      mechanisms mediate the synergistic antinociceptive effects of acetaminophen
      combinations. Despite the presence of a cannabinoid mechanism, synergism was not
      present in all acetaminophen combinations. The combination of currently available
      drugs may be an appropriate option in ameliorating neuropathic SCI pain if single
      drug therapy is ineffective.

PMID- 20035776
TI  - Can overeating induce conditioned taste avoidance in previously food restricted
      rats?
AB  - While feeding is rewarding, the feeling of satiation has been theorized to have a
      mixed affect. Using a food restriction model of overeating we examined whether
      bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male
      Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50%
      of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all
      rats were given access to a novel saccharin solution in place of water, and two
      groups of food restricted rats were given access to either 100% of regular food
      consumption or ad lib food. Ad lib access in the restricted rats induced
      significant overeating on all three exposures. After all rats were returned to ad
      lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly
      reduced saccharin consumption in the overeating rats, compared to those in the
      other 3 groups. To determine whether this avoidance was due to a learned
      association, a second experiment used a latent inhibition paradigm, familiarizing
      half the rats with the saccharin for 8 days prior to pairing it with overeating.
      Using the design of Experiment 1, with only the continuously ad lib and the
      restricted to ad lib feeding groups, it was found that the overeating-induced
      saccharin avoidance was attenuated by the pre-exposure. These results suggest
      that self-induced overeating is capable of supporting a learned avoidance of a
      novel solution suggestive of a conditioned satiety or taste avoidance.

PMID- 20035777
TI  - FURO/CAP: a protocol for sodium intake sensitization.
AB  - We investigated if a history of FURO/CAP, a protocol that increases brain
      angiotensin II (ANG II), sensitizes or enhances sodium intake. A subcutaneous
      injection of the diuretic furosemide (FURO, 10mg/kg) was combined with a
      converting enzyme inhibitor captopril (CAP, 5mg/kg) to induce a short latency
      stimulated sodium (0.3M NaCl) and water intake in a 2h FURO/CAP test. Repeated
      injections of only FURO/CAP, separated by one-week interval, enhanced stimulated
      and spontaneous (daily) sodium intake. Stimulated fluid intake was completely
      suppressed when FURO/CAP was combined with two intraperitoneal injections of the
      ANG II type-1 receptor antagonist losartan (10, 20, or 40 mg/kg each) given
      within 1h prior to the FURO/CAP test. Losartan reduced by only 35% the FURO/CAP
      induced natriuresis. A history of FURO/CAP, FURO/CAP+losartan (all doses), or
      vehicle produced similar stimulated fluid intake when all animals received only
      FURO/CAP in the third final FURO/CAP test. However, a history of vehicle or
      FURO/CAP+losartan 10mg/kg precluded the enhancement in spontaneous sodium intake
      after the third final FURO/CAP. The FURO/CAP combined with losartan (all doses)
      also precluded the spontaneous sodium intake enhancement in the weeks that
      preceded the third final FURO/CAP test. A history of only FURO/CAP, but not
      vehicle, also enhanced water deprivation-induced sodium appetite. The results
      suggest that a history of FURO/CAP enhances stimulated and spontaneous sodium
      intake, as well as water deprivation-induced sodium appetite, and reinforce the
      role of ANG II as a peptide that mediates long-term effects on behavior.

PMID- 20035778
TI  - The limits of regulatory toxicology.
AB  - The Acceptable Daily Intake (ADI) has been used by regulatory and public health
      organizations (e.g., the U.S. Food and Drug and Administration, and the World
      Health Organization) for chemicals for more than 50 years. The ADI concept was
      also initially employed at the U.S. Environmental Protection Agency at its
      inception in 1971, although with the adoption of newer terminology, it later
      became known as the Reference Dose (RfD). It is clear from the literature that
      both were first devised as instruments of regulatory policy. In the intervening
      years, it has become common to use language that implies that these standards are
      statements of scientific fact. Similarly, some of the discretionary or default
      values that are used to derive regulatory standards are represented as scientific
      assumptions when in fact they also represent regulatory policy. This confusion
      impedes both the best use of the available science and informed public
      participation in policy making. In addition, the misconception of the ADI or the
      RfD as statements of scientific fact may impede the consideration of alternative
      means to reduce exposure to chemicals that may be harmful, including regulatory
      measures that do not involve prescribing a regulatory concentration limit.

PMID- 20035779
TI  - Platelet aggregation inhibitors from hematophagous animals.
AB  - Salivary glands from blood-sucking animals (e.g., mosquitoes, bugs, sand flies,
      fleas, ticks, leeches, hookworms, bats) are a rich source of bioactive molecules
      that counteract hemostasis in a redundant and synergistic manner. This review
      discusses recent progress in the identification of salivary inhibitors of
      platelet aggregation, their molecular characterization, and detailed mechanism of
      action. Diversity of inhibitors is remarkable, with distinct families of proteins
      characterized as apyrases that enzymatically degrade ADP or as collagen-binding
      proteins that prevent its interaction with vWF, or platelet integrin alpha2beta1
      or GPVI. Molecules that bind ADP, TXA(2), epinephrine, or serotonin with high
      affinity have also been cloned, expressed, and their structure determined. In
      addition, a repertoire of antithrombins and an increasingly number of RGD and non
      RGD disintegrins targeting platelet alphaIIbbeta3 have been reported. Moreover,
      metalloproteases with fibrinogen(olytic) activity and PAF phosphorylcholine
      hydrolase are enzymes that have been recruited to the salivary gland to block
      platelet aggregation. Platelet inhibitory prostaglandins,
      lysophosphatydilcholine, adenosine, and nitric oxide (NO)-carrying proteins are
      other notable examples of molecules from hematophagous salivary secretions
      (herein named sialogenins) with antihemostatic properties. Sialogenins have been
      employed as tools in biochemistry and cell biology and also display potential
      therapeutic applications.

PMID- 20035780
TI  - Paralytic shellfish poisoning: seafood safety and human health perspectives.
AB  - Paralytic shellfish poisoning (PSP) is the foodborne illness associated with the
      consumption of seafood products contaminated with the neurotoxins known
      collectively as saxitoxins (STXs). This family of neurotoxins binds to voltage
      gated sodium channels, thereby attenuating action potentials by preventing the
      passage of sodium ions across the membrane. Symptoms include tingling, numbness,
      headaches, weakness and difficulty breathing. Medical treatment is to provide
      respiratory support, without which the prognosis can be fatal. To protect human
      health, seafood harvesting bans are in effect when toxins exceed a safe action
      level (typically 80 microg STX eq 100 g(-1) tissue). Though worldwide fatalities
      have occurred, successful management and monitoring programs have minimized PSP
      cases and associated deaths. Much is known about the toxin sources, primarily
      certain dinoflagellate species, and there is extensive information on toxin
      transfer to traditional vectors - filter-feeding molluscan bivalves. Non
      traditional vectors, such as puffer fish and lobster, may also pose a risk. Rapid
      and reliable detection methods are critical for toxin monitoring in a wide range
      of matrices, and these methods must be appropriately validated for regulatory
      purposes. This paper highlights PSP seafood safety concerns, documented human
      cases, applied detection methods as well as monitoring and management strategies
      for preventing PSP-contaminated seafood products from entering the food supply.

PMID- 20035781
TI  - The effects of chronic nicotine on meal patterns, food intake, metabolism and
      body weight of male rats.
AB  - It is unclear what contribution food intake and metabolism have in causing weight
      loss after administering a dose of nicotine equivalent to smoking one to three
      packs of cigarettes per day because previous studies have been of a very short
      duration. To address this question, male Sprague Dawley rats were housed in
      computerized food intake modules and fed 45 mg pellets: Group 1 [nicotine
      injected with 1.4 mg/kg/day (free base), fed ad libitum]; and Group 2 [saline
      injected and pair-fed by computer with Group 2]; and Group 3 [saline injected
      (i.p.), fed ad libitum]. The rats received 4 equally spaced injections over the
      dark phase. Treatment consisted of: Phase 1 (nicotine or saline for 14 days),
      Phase 2 (all rats saline for 8 days and Phase 3 (pair-fed group "unyoked" for 6
      days)). Nicotine inhibited food intake over the first 6 days. On termination of
      nicotine, there was no compensatory hyperphagia in either Groups 1 or 2; and
      their body weight was reduced starting on day 5 until day 28. In another study,
      rats were housed in an indirect calorimetry system. Saline or nicotine was
      injected for 14 days, as noted above; then all rats were injected with saline for
      4 days and then no injections for 10 days to follow changes in body weight.
      Energy expenditure (Kcal/Kg(0.75)) was measured for 18 days. Nicotine
      significantly reduced food intake on 7 of 14 days of nicotine injections. The
      body weight of the nicotine injected rats was significantly reduced starting on
      day 3 until day 25. There were no differences in energy expenditures of the
      groups, which suggested that a decrease in food intake and not an increase in
      metabolism was the reason the rats lost weight after administering nicotine.

PMID- 20035782
TI  - Post-weaning social isolation increases activity in a novel environment but
      decreases defensive burying and subchronic MK-801 enhances the activity but not
      the burying effect in rats.
AB  - Subchronic treatment with a non-competitive glutamate NMDA-receptor antagonist
      [e.g., MK-801 or phencyclidine] or social isolation (SI) from weaning (age 21
      days) to adulthood (age 56 days) produce deficits similar to some of the positive
      and negative symptoms of schizophrenia. Few studies have evaluated the effects of
      these treatments on emotional behavior. We hypothesized that subchronic MK-801,
      post-weaning SI or the two in combination would alter activity in a novel
      environment, anxiety-like behaviors in the elevated plus-maze, coping responses
      in the defensive burying paradigm and social behavior. In experiment 1, SI rats
      (n=17) showed increased locomotor activity when exposed to a novel environment,
      no change in plus-maze behavior and decreased defensive burying when compared to
      group housed rats (n=16). Subchronic MK-801 enhanced the increase in activity but
      not the decrease in burying in SI rats. Experiment 2 evaluated the effects on
      social behavior of post-weaning SI. The locomotor and burying results of
      experiment 1 were replicated and SI rats (n=9) were found to decrease orientation
      towards a novel conspecific social target when compared to group housed rats
      (n=8). The behavioral abnormalities of SI rats may be a manifestation of
      GABAergic dysfunction that has recently become evident in schizophrenia.

PMID- 20035783
TI  - Syneresis in agar hydrogels.
AB  - Agar hydrogels exhibit syneresis which creates internal osmotic stress on the
      physical network. It was observed that such a stress gives rise to characteristic
      pulsating modes (breathing modes). Experiments carried over a period of 60-day
      revealed that the network deformations grew monotonously when the solvent
      released by syneresis was removed periodically from gel surface. However, when
      the solvent was not withdrawn, the gel exhibited very slowly relaxing breathing
      modes. The swelling-deswelling dynamics has been discussed in the generalized
      framework of a dissipative damped oscillator.

PMID- 20035784
TI  - Physicochemical and biological activity study of genipin-crosslinked chitosan
      scaffolds prepared by using supercritical carbon dioxide for tissue engineering
      applications.
AB  - The present study deals with the preparation of porous chitosan scaffolds by
      using a greener technique i.e., supercritical carbon dioxide (sc.CO2). 0.2 M
      chitosan (CS) solution in aqueous acetic acid was treated with 4% (w/v) genipin
      solution; the resulting hydrogels were subjected to solvent exchange prior to the
      final treatment procedures. Their morphology, pore structure, and physical
      properties were characterized by thermal analysis, X-ray diffractogram (XRD),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM) and
      the specific surface areas and porosimetry of scaffolds were determined by using
      N2 adsorption. The biological activity of scaffolds was investigated by immersing
      them into 1.5 x simulated body fluid (SBF) and cellular attachment study was
      assessed using Alamar Blue assay by seeding MG63 osteoblastic cells onto the
      scaffolds. The sc.CO2 assisted chitosan scaffold prepared by using green
      chemistry approach is highly pure and bioactive and can be served as a potential
      material for tissue engineering applications.

PMID- 20035785
TI  - Epidemiology of invasive pneumococcal disease in the pre-conjugate vaccine era:
      England and Wales, 1996-2006.
AB  - OBJECTIVE: To describe the epidemiology of invasive pneumococcal disease (IPD) in
      England & Wales in the pre-conjugate vaccine era. METHODS: We analysed reports of
      culture-confirmed IPD submitted to the national surveillance system between July
      1996 and June 2006. RESULTS: The incidence of IPD was 10 per 100,000 overall, and
      increased over time. The typical pattern of IPD by age was observed, with the
      highest incidence in young children and older adults. There was little change in
      IPD incidence in the elderly, despite the widespread use of 23-valent
      pneumococcal polysaccharide vaccines since 2003. The distribution of serotypes
      changed over time; notably the proportion of cases caused by serotype 14
      decreased, and the proportion due to serotype 1 increased. The incidence of
      meningitis was 0.6 per 100,000 overall, and as a proportion of all IPD cases was
      most common in children under 1 year of age (30%). Particular serotypes were
      significantly associated with a presentation of meningitis, after controlling for
      age and year, and the case:carrier ratio varied markedly by serotype.
      CONCLUSIONS: This paper provides a baseline for evaluating the impact of 7-valent
      pneumococcal conjugate vaccines, introduced in September 2006. Ongoing high
      quality laboratory-based surveillance of IPD in all age groups is essential.

PMID- 20035786
TI  - Spectrum of neurological disease in patients with discordant HIV-1 RNA levels in
      plasma and cerebrospinal fluid.

PMID- 20035787
TI  - The ERP PCA Toolkit: an open source program for advanced statistical analysis of
      event-related potential data.
AB  - This article presents an open source Matlab program, the ERP PCA (EP) Toolkit,
      for facilitating the multivariate decomposition and analysis of event-related
      potential data. This program is intended to supplement existing ERP analysis
      programs by providing functions for conducting artifact correction, robust
      averaging, referencing and baseline correction, data editing and visualization,
      principal components analysis, and robust inferential statistical analysis. This
      program subserves three major goals: (1) optimizing analysis of noisy data, such
      as clinical or developmental; (2) facilitating the multivariate decomposition of
      ERP data into its constituent components; (3) increasing the transparency of
      analysis operations by providing direct visualization of the corresponding
      waveforms.

PMID- 20035788
TI  - ISG15 over-expression inhibits replication of the Japanese encephalitis virus in
      human medulloblastoma cells.
AB  - IFN-stimulated gene 15 (ISG15), an ubiquitin-like protein, is rapidly induced by
      IFN-alpha/beta, and ISG15 conjugation is associated with the antiviral immune
      response. Japanese encephalitis virus (JEV), a mosquito-borne neurotropic
      flavivirus, causes severe central nervous system diseases. We investigated the
      potential anti-JEV effect of ISG15 over-expression. ISG15 over-expression in
      human medulloblastoma cells significantly reduced the JEV-induced cytopathic
      effect and inhibited JEV replication by reducing the viral titers and genomes
      (p<0.05, Student's t-test); it also increased activation of the interferon
      stimulatory response element (ISRE)-luciferase cis-acting reporter in JEV
      infected cells (p<0.05, Chi-square test). Furthermore, Western blotting revealed
      that ISG15 over-expression increased phosphorylation of IRF-3 (Ser396), JAK2
      (Tyr1007/1008) and STAT1 (Tyr701 and Ser727) in JEV-infected cells (P<0.05, Chi
      square test). Confocal imaging indicated that nucleus translocation of
      transcription factor STAT1 occurred in ISG15-over-expressing cells but not in
      vector control cells post-JEV infection. ISG15 over-expression activated the
      expression of STAT1-dependent genes including IRF-3, IFN-beta, IL-8, PKR and OAS
      before and post-JEV infection (p=0.063, Student's t-test). The results enabled
      elucidation of the molecular mechanism of ISG15 over-expression against JEV,
      which will be useful for developing a novel treatment to combat JEV infection.

PMID- 20035789
TI  - Sleep enhances false memories depending on general memory performance.
AB  - Memory is subject to dynamic changes, sometimes giving rise to the formation of
      false memories due to biased processes of consolidation or retrieval. Sleep is
      known to benefit memory consolidation through an active reorganization of
      representations whereas acute sleep deprivation impairs retrieval functions.
      Here, we investigated whether sleep after learning and sleep deprivation at
      retrieval enhance the generation of false memories in a free recall test.
      According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects
      learned lists of semantically associated words (e.g., "night", "dark", "coal",
      etc.), lacking the strongest common associate or theme word (here: "black"). Free
      recall was tested after 9h following a night of sleep, a night of wakefulness
      (sleep deprivation) or daytime wakefulness. Compared with memory performance
      after a retention period of daytime wakefulness, both post-learning nocturnal
      sleep as well as acute sleep deprivation at retrieval significantly enhanced
      false recall of theme words. However, these effects were only observed in
      subjects with low general memory performance. These data point to two different
      ways in which sleep affects false memory generation through semantic
      generalization: one acts during consolidation on the memory trace per se,
      presumably by active reorganization of the trace in the post-learning sleep
      period. The other is related to the recovery function of sleep and affects
      cognitive control processes of retrieval. Both effects are unmasked when the
      material is relatively weakly encoded.

PMID- 20035790
TI  - Hypothalamic nutrient sensing in the control of energy homeostasis.
AB  - The hypothalamus is a center of convergence and integration of multiple nutrient
      related signals. It can sense changes in circulating adiposity hormones, gastric
      hormones and nutrients, and receives neuroanatomical projections from other
      nutrient sensors, mainly within the brainstem. The hypothalamus also integrates
      these signals with various cognitive forebrain-descending information and
      reward/motivation-related signals coming from the midbrain-dopamine system, to
      coordinate neuroendocrine, behavioral and metabolic effectors of energy balance.
      Some of the key nutrient-sensing hypothalamic neurons have been identified in the
      arcuate, the ventro-medial and the lateral nuclei of the hypothalamus, and the
      molecular mechanisms underlying intracellular integration of nutrient-related
      signals in these neurons are currently under intensive investigation. However,
      little is known about the neural pathways downstream from hypothalamic nutrient
      sensors, and how they drive effectors of energy homeostasis under physiological
      conditions. This manuscript will review recent progress from molecular, genetic
      and neurophysiological studies that identify and characterize the critical
      intracellular signalling pathways and neurocircuits involved in determining
      hypothalamic nutrient detection, and link these circuits to behavioral and
      metabolic effectors of energy balance. We will provide a critical analysis of
      current data to identify ongoing challenges for future research in this field.

PMID- 20035791
TI  - Neurons recruited in the nidopallium caudale, following changes in social
      environment, derive from the same original population.
AB  - Previously, we found that new neurons recruited into the nidopallium caudale in
      isolated birds were less labeled than those of communally housed birds,
      suggesting that different types of neurons may survive best under different
      conditions. Repetition of the experiment revealed no differences between groups,
      indicating that the new neurons were of the same generation. Hence, social
      environment does not appear to affect the type of newly recruited nidopallium
      caudale neurons.

PMID- 20035792
TI  - The effect of early experience on odor perception in humans: psychological and
      physiological correlates.
AB  - The olfactory function in humans is characterized by wide variability between
      individuals. One of the prominent factors that contribute to this plasticity is
      early exposure. The present study examined how brain activity is modulated by
      such olfactory experience. To this end, two groups of people living in France but
      originating from different cultures ("European-French" (EF, 18 subjects) vs.
      "Algerian-French" (AF, 19 subjects)) were tested, and their perceptual and
      physiological responses to the smells of mint (presumed to be experienced earlier
      in life by "Algerian-French" subjects) and of rose (control odorant) were
      compared. Neurophysiological responses were obtained in the form of chemosensory
      event-related potentials (CSERP). The results confirmed that the AF group was
      exposed to Mint tea earlier than the EF group. On the perceptual level, when
      asked to associate the smell of mint with objects or events retrieved from
      memory, the discourse of AF subjects included more "experience-oriented"
      associations than that of EF subjects. This was associated with longer P2 latency
      in CSERPs in response to the smell of mint in the AF group. These findings
      highlight the plasticity of behavioral and neural olfactory processes as a result
      of differential lifetime exposure.

PMID- 20035793
TI  - Nest building performance following MPTP toxicity in mice.
AB  - Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice
      is one of the primary models used to evaluate neuroprotective and symptomatic
      treatment strategies for Parkinson's disease. Many behavioral methods for
      evaluation of MPTP toxicity have been described, but they often involve
      challenging scenarios that require handling and transfer of animals to novel
      environments and in some cases prior animal training. These factors can
      profoundly influence animal behavior and potentially influence experimental
      outcome. Presented here is a new nest building scoring paradigm based on the
      animals' normal home cage behavior that is a simple, non-invasive, and
      reproducible measure for estimating neurological dysfunction in MPTP intoxicated
      mice. Nest building behavior requires orofacial and forelimb movement and has
      been shown to be dopamine-dependent making it a possible method for assessing
      parkinsonian-like symptoms. Significant deficits in nest building scores after
      2x20 and 2x25 mg/kg MPTP coincided with a 90% reduction in striatal dopamine.
      Nest building deficits could be detected for more than a week after intoxication.
      However, after 28 days the change in behavior was no longer detected, which may
      reflect the plasticity of the tyrosine hydroxylase positive neurons in the
      dorsolateral part of striatum.

PMID- 20035794
TI  - Analyzing habituation responses to novelty in zebrafish (Danio rerio).
AB  - Analysis of habituation is widely used to characterize animal cognitive
      phenotypes and their modulation. Although zebrafish (Danio rerio) are
      increasingly utilized in neurobehavioral research, their habituation responses
      have not been extensively investigated. Utilizing the novel tank test, we examine
      intra- and inter-session habituation and demonstrate robust habituation responses
      in adult zebrafish. Analyzing the intra-session habituation to novelty further,
      we also show that selected anxiogenic drugs (caffeine, pentylenetetrazole), as
      well as stress-inducing alarm pheromone, attenuated zebrafish habituation. Some
      acute anxiolytic agents, such as morphine and ethanol, while predictably reducing
      zebrafish anxiety, had no effects on habituation. Chronic ethanol and fluoxetine
      treatments improved intra-session habituation in zebrafish. In general, our study
      parallels literature on rodent habituation responses to novelty, and reconfirms
      zebrafish as a promising model for cognitive neurobehavioral research.

PMID- 20035796
TI  - The temporal specificity of the switch from NMDAr-dependent extinction to NMDAr
      independent re-extinction.
AB  - Recent findings show that the switch from NMDAr-dependent extinction to NMDAr
      independent re-extinction is both context and stimulus specific. In this study we
      examined whether this switch was temporally specific as well. Re-extinction was
      found to be NMDAr-independent when it occurred 2 days after initial extinction
      but NMDAr-dependent when it occurred 21 days following initial extinction,
      thereby illustrating the importance of time as a type of context that modulates
      the mechanisms involved in extinction.

PMID- 20035795
TI  - Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy.
AB  - We have previously shown that immunotherapy directed against the protein Nogo-A
      leads to recovery on a skilled forelimb reaching task in rats after sensorimotor
      cortex stroke, which correlated with axonal and dendritic plasticity. Here we
      investigated anti-Nogo-A immunotherapy as an intervention to improve performance
      on a spatial memory task in aged rats after stroke, and whether cognitive
      recovery was correlated with structural plasticity. Aged rats underwent a
      unilateral distal permanent middle cerebral artery occlusion and one week later
      were treated with an anti-Nogo-A or control antibody. Nine weeks post-stroke,
      treated rats and normal aged rats were tested on the Morris water maze task.
      Following testing rats were sacrificed and brains processed for the Golgi-Cox
      method. Hippocampal CA3 and CA1 pyramidal and dentate gyrus granule cells were
      examined for dendritic length and number of branch segments, and CA3 and CA1
      pyramidal cells were examined for spine density and morphology. Anti-Nogo-A
      immunotherapy given one week following stroke in aged rats improved performance
      on the reference memory portion of the Morris water maze task. However, this
      improved performance was not correlated with structural changes in the
      hippocampal neurons examined. Our finding of improved performance on the Morris
      water maze in aged rats after stroke and treatment with anti-Nogo-A immunotherapy
      demonstrates the promising therapeutic potential for anti-Nogo-A immunotherapy to
      treat cognitive deficits after stroke. The identification of sites of axonal and
      dendritic plasticity in the aged brain after stroke and treatment with anti-Nogo
      A immunotherapy is still under investigation.

PMID- 20035797
TI  - Differential involvement of the opioid receptor antagonist naloxone in
      motivational and hedonic aspects of reward.
AB  - In the present study dose-dependent effects of the opioid receptor antagonist
      naloxone were investigated on the rewarding effects of sweetened condensed milk
      (SCM) in four behavioral paradigms addressing hedonic, consummatory as well as
      motivational aspects of a reward: odour-conditioned pleasure attenuation of the
      acoustic startle response (PAS), conditioned place preference (CPP), voluntary
      consumption in a limited access paradigm, as well as break point determination in
      a progressive ratio (PR) task. A dose-dependent reduction in reward-related
      behavior was observed in all paradigms, with exception of the break point in the
      PR task, which was not affected by naloxone at all. CPP for SCM was only affected
      by the highest dose of naloxone. The present results indicate that naloxone is
      more effective in suppressing the hedonic than motivational aspects of reward,
      further supporting the involvement of the endogenous opioid system in the
      mediation of hedonic properties of food reward.

PMID- 20035798
TI  - Combined administration of alpha1-adrenoceptor antagonist prazosin and beta
      blocker propranolol impairs spatial avoidance learning on a dry arena.
AB  - Spatial learning is a widely studied type of animal behavior often considered as
      a model of higher human cognitive functions. Noradrenergic receptors play a
      modulatory role in many nerve functions, including vigilance, attention, reward,
      learning and memory. The present study aimed at studying the effects of separate
      or combined systemic administration of the alpha1-adrenergic antagonist prazosin
      (1 and 2 mg/kg) and beta-blocker propranolol (5 and 20 mg/kg) on the hippocampus
      dependent learning in the active allothetic place avoidance (AAPA) task. Both
      centrally active drugs impaired spatial learning when administered together,
      exerting no effect in separate applications. Locomotion was impaired only in a
      combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg
      propranolol). These results suggest an in vivo interaction between these two
      types of receptors in spatial navigation regulation.

PMID- 20035799
TI  - The uncertainty processing theory of motivation.
AB  - Most theories describe motivation using basic terminology (drive, 'wanting',
      goal, pleasure, etc.) that fails to inform well about the psychological
      mechanisms controlling its expression. This leads to a conception of motivation
      as a mere psychological state 'emerging' from neurophysiological substrates.
      However, the involvement of motivation in a large number of behavioural
      parameters (triggering, intensity, duration, and directedness) and cognitive
      abilities (learning, memory, decision, etc.) suggest that it should be viewed as
      an information processing system. The uncertainty processing theory (UPT)
      presented here suggests that motivation is the set of cognitive processes
      allowing organisms to extract information from the environment by reducing
      uncertainty about the occurrence of psychologically significant events. This
      processing of information is shown to naturally result in the highlighting of
      specific stimuli. The UPT attempts to solve three major problems: (i) how
      motivations can affect behaviour and cognition so widely, (ii) how motivational
      specificity for objects and events can result from nonspecific
      neuropharmacological causal factors (such as mesolimbic dopamine), and (iii) how
      motivational interactions can be conceived in psychological terms, irrespective
      of their biological correlates. The UPT is in keeping with the conceptual
      tradition of the incentive salience hypothesis while trying to overcome the
      shortcomings inherent to this view.

PMID- 20035800
TI  - Sex differences in human virtual water maze performance: novel measures reveal
      the relative contribution of directional responding and spatial knowledge.
AB  - Sex differences in humans on virtual water maze navigation are well established
      when overall performance is measured, e.g., by the total time taken to find the
      hidden platform, total path length, or quadrant dwell time during probe trials.
      Currently, it is unknown whether males are better spatial learners than females,
      or if overall performance differences reflect other aspects of the task unrelated
      to spatial memory. Here, males and females were tested on a virtual analogue of
      the Morris water maze. We devised a novel method of analysis in which each trial
      was divided into an initial trajectory phase and search phase. We also
      implemented a new measure of spatial learning during early and late training, by
      including trials in which subjects were only required to indicate where they
      thought the hidden target zone was located. Consistent with previous reports,
      males outperformed females on overall measures of task performance. Males also
      performed significantly better on all initial trajectory phase variables.
      Interestingly, only small (non-significant) differences were observed during the
      search phase and when spatial learning was tested without the constraints of a
      typical water maze trial. Our results suggest that spatial knowledge regarding
      the location of the hidden target zone is not the main factor responsible for
      overall sex differences in virtual water maze performance. Instead, the largest
      sex differences were observed during the initial trajectory phase of the trial,
      which is thought to depend on effective processing of distal features of the
      environment.

PMID- 20035801
TI  - The role of neurotensin in positive reinforcement in the rat central nucleus of
      amygdala.
AB  - In the central nervous system neurotensin (NT) acts as a neurotransmitter and
      neuromodulator. It was shown that NT has positive reinforcing effects after its
      direct microinjection into the ventral tegmental area. The central nucleus of
      amygdala (CeA), part of the limbic system, plays an important role in learning,
      memory, regulation of feeding, anxiety and emotional behavior. By means of
      immunohistochemical and radioimmune methods it was shown that the amygdaloid body
      is relatively rich in NT immunoreactive elements and NT receptors. The aim of our
      study was to examine the possible effects of NT on reinforcement and anxiety in
      the CeA. In conditioned place preference test male Wistar rats were microinjected
      bilaterally with 100 or 250 ng NT in volume of 0.4 microl or 35 ng neurotensin
      receptor 1 (NTS1) antagonist SR 48692 alone, or NTS1 antagonist 15 min before 100
      ng NT treatment. Hundred or 250 ng NT significantly increased the time rats spent
      in the treatment quadrant. Prior treatment with the non-peptide NTS1 antagonist
      blocked the effects of NT. Antagonist itself did not influence the reinforcing
      effect. In elevated plus maze test we did not find differences among the groups
      as far as the anxiety index (time spent on the open arms) was concerned. Our
      results suggest that in the rat ACE NT has positive reinforcing effects. We
      clarified that NTS1s are involved in this action. It was also shown that NT does
      not influence anxiety behavior.

PMID- 20035803
TI  - Tactile roughness discrimination threshold is unrelated to tactile spatial
      acuity.
AB  - The present study examined the relationship between the tactile roughness
      discrimination threshold (TRDT) and the tactile spatial resolution threshold
      (TSRT) at the index fingertip in humans. A new device was built for measuring
      TRDT, allowing pair-wise presentations of two sets of six different sandpaper
      grits. The smoothest grits ranged from 18 to 40 microm and the roughest grits
      ranged from 50 to 195 microm particle size. The reference sandpaper had a 46
      microm particle size. A two-alternative forced choice paradigm and a double
      interlaced adaptive staircase procedure yielding a 75% just noticeable difference
      (75%jnd) was used according to Zwislocki and Relkin. Contact force and scanning
      velocity were measured at the fingertip with a built-in sensor. The TSRT was
      assessed with an extended set of grating domes. Fifty-three male and female
      subjects, spanning a wide age range participated in this study. The JND75% or
      TRDT was lower for the smoothest sandpapers (15+/-8.5 microm) compared to the
      roughest sandpapers (44+/-32.5 microm). TRDT performance was unrelated to age or
      gender. Additionally, grit size had no effect on the mean forces (normal and
      tangential) exerted at the fingertip or the mean scan velocities. In contrast,
      there was a significant degradation of TSRT performance with age. Lastly, there
      was no significant correlation between TRDT and TRST performance. Results of this
      study support the theory that the neural mechanisms underlying the perception of
      tactile roughness discrimination for fine textures differ from those involved in
      spatial resolution acuity often associated with the SA1 afferents.

PMID- 20035802
TI  - Planum temporale surface area and grey matter asymmetries in chimpanzees (Pan
      troglodytes): the effect of handedness and comparison with findings in humans.
AB  - The planum temporale (PT) is the bank of tissue that lies posterior to Heschl's
      gyrus and is considered a key brain region involved in language and speech in the
      human brain. In the human brain, both the surface area and grey matter volume of
      the PT is larger in the left compared to right hemisphere in approximately 2/3rds
      of individuals, particularly among right-handed individuals. Here we examined
      whether chimpanzees show asymmetries in the PT for grey matter volume and surface
      area in a sample of 103 chimpanzees from magnetic resonance images. The results
      indicated that, overall, the chimpanzees showed population-level leftward
      asymmetries for both surface area and grey matter volumes. Furthermore,
      chimpanzees that prefer to gesture with their right-handed had significantly
      greater leftward grey matter asymmetries compared to ambiguously- and left-handed
      apes. When compared to previously published data in humans, the direction and
      magnitude of PT grey matter asymmetries were similar between humans and apes;
      however, for the surface area measures, the human showed more pronounced leftward
      asymmetries. These results suggest that leftward asymmetries in the PT were
      present in the common ancestor of chimpanzees and humans.

PMID- 20035805
TI  - Sensory neuropeptides are potent chemoattractants for human basophils in vitro.
AB  - The sensory neuropeptides secretoneurin (SN) and substance P (SP) are involved in
      "neurogenic" inflammatory processes as they occur in bronchial asthma or allergic
      rhinitis. A possible interaction with basophils has not been reported to date.
      Basophils were isolated from healthy donors by magnetic cell sorting technique
      and migration was explored using Boyden microchemotaxis chambers. SN [10(-8)M]
      and SP [10(-6) to 10(-8)M] proved to be chemoattractants equally potent to FMLP
      [10(-8)M] or LPS [10 pg/ml]. Specific anti-SN antibodies and a trypsinization
      preparation of SN were used to determine the specificity of the SN effect on
      basophils. The preincubation of basophils with neurokinin-1 (NK-1) or -2 (NK-2)
      receptor antagonists revealed the SP effect to act via NK-1 receptors in
      basophils. In addition, we were able to show phosphodiesterases and
      phosphoinositide-3 kinases to be engaged in the downstream signalling pathway.
      Our observations reveal for the first time a link between basophils, which are
      engaged in allergic processes, and the neuropeptides SN and SP. Furthermore, our
      data might suggest phosphodiesterases or phosphoinositide-3 kinases to be new
      therapeutic targets for the treatment of allergic diseases such as asthma or
      allergic rhinitis.

PMID- 20035804
TI  - Contribution of endogenous nitrergic and peptidergic influences to the altered
      neurally-induced gastric contractile responses in strips from dystrophic (mdx)
      mice.
AB  - Gastrointestinal motor disorders have been reported to occur in dystrophic (mdx)
      mice. The aim of the present study was to investigate the contribution of
      endogenous nitrergic and peptidergic components to the gastric contractile
      responses in strips from wild type (WT) and mdx mice. In both preparations,
      electrical field stimulation (EFS) induced frequency-dependent excitatory
      responses that were abolished by atropine or tetrodotoxin. The amplitude of the
      neurally-induced contractile responses was greater in strips from mdx mice in
      respect to the WT ones. In both preparations, at the end of the stimulation
      period strip tension decayed below the pre-stimulus level (off-relaxations). The
      nitric oxide (NO) synthesis inhibitor L-NNA increased the amplitude of the EFS
      induced contractile responses without influencing off-relaxations. alpha
      chymotrypsin and PACAP 6-38 abolished off-relaxations and also caused a reduction
      in amplitude of the contractile responses, whereas VIP receptor antagonists were
      ineffective. The efficacy of L-NNA, alpha-chymotrypsin or PACAP 6-38 on the
      excitatory responses was lower in strips from mdx mice in respect to the WT ones.
      alpha-chymotrypsin, in the presence of L-NNA, was no longer able to decrease the
      amplitude of the neurally-induced contractile responses but still abolished off
      relaxations in both preparations. Direct muscular responses to methacholine were
      similar in amplitude in the two preparations and were not influenced by L-NNA or
      alpha-chymotrypsin. The results indicate that both endogenous NO and peptides
      influence the EFS-induced cholinergic responses: a stronger peptidergic
      modulatory action on a weaker nitrergic neurotransmission is suggested to occur
      in strips from mdx mice in respect to the WT ones and to contribute to the
      altered gastric contractile responses.

PMID- 20035806
TI  - Chamber-dependent circadian expression of cardiac natriuretic peptides.
AB  - Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have
      important local functions within the myocardium, where they protect against
      accelerated fibrosis. As circadian expression of cardiac natriuretic peptides
      could be of importance in local cardiac protection against disease, we examined
      the diurnal changes of the mRNAs encoding ANP, BNP, and their common receptor NPR
      A in atrial and ventricular myocardium. Forty eight mice were killed at the
      following ZT times: 4, 8, 12, 16, 20, and 24, where ZT designates Zeitgeber; ZT 0
      corresponds to lights ON and ZT 12 corresponds to lights OFF. Eight animals (4
      males and 4 females) were included at each time point. Another 48 animals were
      killed during the second cycle of dark/dark (designated Circadian Time or CT: CT
      4, CT 8, CT 12, CT 16, CT 20, and CT 24). The cellular contents of the clock
      genes Per1 and Bmal1 as well as ANP, BNP, and their common receptor (NPR-A) were
      determined using RT-PCR. Per1 and Bmal1 mRNA contents oscillated in antiphase in
      both atrial and ventricular regions, where Bmal1 mRNA peaked 12h out of phase
      relative to Per1 mRNA. ANP and NPR-A atrial mRNA contents revealed borderline
      significant diurnal changes, whereas ventricular BNP mRNA contents exhibited
      pronounced oscillation during constant darkness with nadir at CT 12 (P<0.0001).
      In conclusion, we report a chamber-dependent circadian profile of cardiac BNP
      mRNA contents, which is not paralleled by the related ANP gene. Our findings
      suggest that the BNP mRNA pattern could be associated with increased cardiac
      susceptibility and response to disease.

PMID- 20035807
TI  - Diagnostic microarray for human and animal bacterial diseases and their virulence
      and antimicrobial resistance genes.
AB  - Rapid diagnosis and treatment of disease is often based on the identification and
      characterization of causative agents derived from phenotypic characteristics.
      Current methods can be laborious and time-consuming, often requiring many skilled
      personnel and a large amount of lab space. The objective of our study was to
      develop a spotted microarray for rapid identification and characterization of
      bacterial pathogens and their antimicrobial resistance genes. Our spotted
      microarray consists of 489 70mer probes that detect 40 bacterial pathogens of
      medical, veterinary and zoonotic importance (including 15 NIAID Category A, B and
      C pathogens); associated genes that encode resistance for antimicrobial and metal
      resistance; and DNA elements that are important for horizontal gene transfer
      among bacteria. High specificity and reliability of the microarray was achieved
      for bacterial pathogens of animal and human importance by validating MDR
      pathogenic bacteria as pure cultures or by following their inoculation in complex
      and highly organic sample matrices, such as soil and manure.

PMID- 20035808
TI  - Differential carbon source utilization by Campylobacter jejuni 11168 in response
      to growth temperature variation.
AB  - Campylobacter spp. readily colonize the intestinal tracts of both human and avian
      species. While most often commensal organisms in birds, campylobacters remain the
      leading cause of bacterial gastroenteritis in humans. The association of
      campylobacters with poultry is well established as a primary route for human
      exposure. The difference in normal core body temperature between chickens (42
      degrees C) and humans (37 degrees C) has been suggested to trigger potential
      colonization or virulence factors and investigators have demonstrated
      differential gene expression at the two temperatures. Campylobacter spp. exhibit
      unique nutritional requirements and have been thought to only utilize amino acids
      and Kreb cycle intermediates as carbon sources for growth. We evaluated the
      ability of the genome-sequenced strain of Campylobacter jejuni 11168 (GS) to
      oxidize 190 different substrates as sole carbon sources at 37 degrees C and 42
      degrees C using phenotype microarray (PM) technology. Results indicate that the
      expected amino acids, l-serine, l-aspartic acid, l-asparagine, and l-glutamic
      acid were utilized in addition to a number of organic acids. In general,
      oxidation of the substrates was greater at 42 degrees C than at 37 degrees C with
      a few exceptions. By employing the PM method, we observed a number of potential
      false-positive reactions for substrates including the triose, dihydroxyacetone;
      and the pentose sugars, d-xylose, d-ribose, l-lyxose, and d- and l-arabinose. The
      presence of genes possibly responsible for utilization of pentose sugars is
      supported by the genomic sequence data, but actual utilization as sole carbon
      sources for active respiration has not been observed. A better understanding of
      the metabolic pathways and nutritional requirements of campylobacters could lead
      to improvements in culture media for detection and isolation of the pathogen and
      to future intervention methods to reduce human exposure.

PMID- 20035809
TI  - Intratracheally instilled mannosylated cationic liposome/NFkappaB decoy complexes
      for effective prevention of LPS-induced lung inflammation.
AB  - The nuclear factor kappa B (NFkappaB) signaling pathway is a key mechanism in the
      pathophysiology of lung inflammation. NFkappaB is critically responsible for the
      expression of pro-inflammatory mediators following activation. The specific
      inhibition of NFkappaB by a NFkappaB decoy via inhalation appears to improve
      therapeutic effects. However, administration of naked NFkappaB decoy limits the
      efficacy of the decoy strategy due to low targeting ability to immune cells such
      as alveolar macrophages. In this study, we have assessed the effect of alveolar
      macrophage-targeted NFkappaB decoy by mannosylated (Man) cationic liposomes in a
      LPS-induced lung inflammation model after intratracheal administration. The
      complex of Man-cationic liposome/NFkappaB decoy was physically stable during
      spraying. Man-cationic liposome/NFkappaB decoy complex was selectively delivered
      to alveolar macrophages for subsequent localization of NFkappaB decoy in the
      cytoplasm and to a lesser extent in the nucleus. In the LPS-induced lung
      inflammation model, pre-treatment with Man-cationic liposome/50MUg NFkappaB decoy
      complex significantly inhibited the release of TNF-alpha, IL-1beta and CINC-1,
      neutrophil infiltration and NFkappaB activation compared with naked NFkappaB
      decoy, cationic liposome/NFkappaB decoy complex and Man-cationic
      liposome/scrambled decoy complex treatments. This study demonstrates the
      sufficient targeting of NFkappaB decoy using Man-cationic liposomes in a novel
      effective anti-inflammatory therapy for lung inflammation.

PMID- 20035810
TI  - Monitoring intracellular degradation of exogenous DNA using diffusion properties.
AB  - Artificial nonviral gene vectors have the potential to improve the safety of gene
      therapy; however, such artificial vectors are less efficient for gene expression
      due to the existence of various barriers to delivery of exogenous DNAs to the
      nucleus in the living cell. Here we describe the degradation activities of
      cytoplasmic nucleases, which are involved as a barrier to efficient exogenous
      gene expression. The size and structure of degraded DNA were monitored by
      fluorescence correlation spectroscopy (FCS) and fluorescence cross-correlation
      spectroscopy (FCCS) in solution and in the cytoplasm of living cells. Differences
      in degradation by endo- and exonucleases were confirmed by differences in the
      size and structure of DNA. Moreover, we confirmed the influence of the
      exonuclease degradation in cytoplasm on the expression rate of DNA transfection
      with a cationic lipid. Based on a comparison of in vitro and cell measurements,
      we conclude that cytoplasmic degradation by exonucleases can be a considerable
      barrier against efficient gene delivery.

PMID- 20035811
TI  - Collagen nerve conduits releasing the neurotrophic factors GDNF and NGF.
AB  - Artificial nerve conduits (NC) can clinically be instrumental for facilitating
      the surgery of damaged peripheral nerves. To improve axonal regeneration of
      injured peripheral nerves, we have developed collagen nerve conduits (NC)
      releasing glial cell line-derived neurotrophic factor (GDNF) alone or in
      combination with nerve growth factor (NGF), which exert synergistic action on
      axonal growth. Degradation of the NC and their mechanical and drug release
      properties were controlled by two means: (i) cross-linking the collagen tubes by
      physical means, through a dehydro-thermal treatment (DHT), before loading with
      the neurotrophic factors (NTFs) GDNF or GDNF/NGF; and (ii) coating the drug
      loaded collagen tubes with layers of poly(lactide-co-glycolide) (PLGA). Non-cross
      linked collagen NC (C-NC) released high amounts of NTFs during the initial 2-3
      days of incubation, whereas the DHT-treated collagen NC (C(dht)-NC) did not show
      a prominent burst effect. The release kinetics was similar for GDNF alone and
      GDNF co-delivered with NGF. Within 30 days, the C-NC released 78% and 83% of the
      total doses of GDNF and NGF, respectively, whereas the C(dht)-NC released only
      68% of GDNF and 56% of NGF. The bioactivity of the NTFs released up to 30 days
      was confirmed by an in vitro bioassay using chicken embryonic dorsal root
      ganglion (DRG) explants. The C(dht)-NC also possessed adequate mechanical
      resistance against radial compression, the pull-out of a suture thread, and loss
      of patency upon bending. Modulus and pull-out strength increased in the order of
      C-NC, C(dht)-NC approximately Neuragen, and Neurolac, with the latter two
      products being commercially available collagen and polyester NC, respectively. In
      vitro degradation time upon incubation with collagenase increased in the same
      order for the collagen-based NC. In conclusion, co-delivery of synergistically
      acting GDNF and NGF from structurally improved NC may be a promising tool for the
      successful repair of peripheral nerve defects.

PMID- 20035812
TI  - Effects of Endokinin A/B and Endokinin C/D on the antinociception of Endomorphin
      1 in mice.
AB  - In our previous study, Endokinin A/B (EKA/B, the common C-terminal decapeptide in
      Endokinin A and Endokinin B) was found to induce analgesic effect at high dose
      and nociception at low dose, while Endokinin C/D (EKC/D, the common C-terminal
      duodecapeptide in Endokinin C and Endokinin D) has analgesic effect only. So in
      this study an attempt was undertaken to investigate the interaction of EKA/B and
      EKC/D with Endomorphin-1 (EM-1) on antinociceptive effect at supraspinal level.
      Results showed that the antinociceptive effect of EM-1 was enhanced by high dose
      of EKA/B and abolished by low dose of EKA/B, while EKC/D could only enhance the
      analgesic effect. Mechanism studies showed that EKA/B blocked the antinociception
      of EM-1 by activating neurokinin-1 receptor (NK(1)), whose specific antagonist,
      SR140333B could fully block EKA/B-induced attenuation on the analgesic response
      of EM-1. Surprisingly, EKC/D could also block the same EKA/B-induced attenuation.
      Taken together, the different effects of EKA/B and EKC/D on the antinociception
      of EM-1 may pave the way for a new strategy on investigating the interaction
      between tachykinins and opioids on pain modulation.

PMID- 20035813
TI  - Milk versus caseinophosphopeptides added to fruit beverage: resistance and
      release from simulated gastrointestinal digestion.
AB  - The influence of simulated gastrointestinal digestion on caseinophosphopeptides
      (CPPs) formation in milk-based fruit beverage was evaluated, together with
      resistance of a pool of CPPs added to fruit beverage. In milk-based fruit
      beverage, four CPPs were identified that can be justified by their presence in
      raw milk or due to processing. When it was subjected to simulated
      gastrointestinal digestion, 10 CPPs were identified, and only 1 presented the
      cluster (SpSpSpEE) (3 phosphoseryl group followed by 2 glutamic acid residues),
      which corresponded to alpha(s2)-CN(1-19)4P. CPPs added to fruit beverage are
      resistant to simulated gastrointestinal digestion, and 16 CPPs were identified
      originating from the fragmentation of added CPPs, and with a greater presence of
      the cluster compared with CPPs originating from milk-based fruit beverage. This
      could justify the use of CPPs as functional ingredients, and offer a good
      alternative to milk-based fruit beverage for improving mineral bioavailability.

PMID- 20035814
TI  - A census of predicted mutational epitopes suitable for immunologic cancer
      control.
AB  - The adaptive immune system can protect against spontaneously arising tumors, and
      the potential exists to reduce cancer incidence by priming adaptive immune
      responses with vaccines. Immunologic cancer control has been implemented for
      cancers caused by infectious agents, but not for spontaneous cancers caused by
      mutation. This is largely due to the high cost of preventative clinical trials
      and the lack of validated tumor epitopes. Here we evaluate, computationally, all
      known somatic mutations in human tumors for their antigenic potential. All
      possible human leukocyte antigen (HLA) class I presented peptides containing
      recurrent somatic cancer mutations with frequency > 5% were screened by three
      independent epitope prediction algorithms (SYFPEITHI, BIMAS, and IEDB). Using
      stringent filters, a total of 20 genes, 35 mutations, and 159 candidate epitopes
      were identified, each presented by up to four distinct HLA class I alleles. The
      top-ranking gene from our survey was KRAS, which figures prominently because
      there are frequent hotspot mutations in numerous, prevalent cancers, and mutant
      peptides are predicted to be presented by several common HLA alleles. From our
      data, we estimate that prophylactic vaccination could provide meaningful levels
      of prevention of tumors associated with common recurrent mutations.

PMID- 20035815
TI  - Rapid genetic screening for major human leukocyte antigen risk haplotypes in
      patients with type 1 diabetes from Northeastern Brazil.
AB  - The aim of this study was to identify in the Brazilian population the frequency
      of human leukocyte antigen (HLA) DQ2.5 and DQ8 haplotypes conferring risk for
      type 1 diabetes (T1D), and to validate a new genotyping method aimed at cost
      reduction and automation. A total of 184 children and adolescents with T1D and
      184 healthy individuals from Recife (northeastern Brazil) were analyzed using the
      conventional polymerase chain reaction-sequence-specific primers HLA genotyping
      and a newly described Tag-single-nucleotide polymorphism real-time polymerase
      chain reaction. The Tag-single-nucleotide polymorphism-based HLA genotyping
      method was successfully validated, proved to be robust, with limited cost and
      thus could be successfully used for the identification of genetic susceptibility
      for T1D in areas with limited financial resources. Our findings report for the
      first time the distribution of DQ2.5 and DQ8 HLA risk haplotypes associated with
      T1D in northeastern Brazil and evidence a major risk for developing T1D when the
      heterozygous DQ2.5/DQ8 or the homozygous DQ2.5/DQ2.5 haplotypes are present.

PMID- 20035816
TI  - Human uptake of persistent chemicals from contaminated soil: PCDD/Fs and PCBs.
AB  - Trace amounts of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and
      polychlorinated biphenyls (PCBs) are ubiquitous in the environment. Because of
      industrial activity, other human activities, and accidents, higher concentrations
      of these chemicals may be present in soil, in residential and recreational areas.
      Human uptake of these chemicals from such soils has been assumed by regulators,
      and people contacting such soils may be concerned about potential adverse health
      effects. Accordingly, clean up levels have been set by state and federal
      agencies. Whether and to what extent humans actually take up these chemicals from
      soil is the focus of this review. Since humans are also exposed to PCDD/Fs and
      PCBs in food and air, their concentrations in these media are presented. We find
      that their presence in soils is unlikely to increase human body burdens.

PMID- 20035817
TI  - Impaired P50 suppression in fear extinction in obsessive-compulsive disorder.
AB  - The processes of fear conditioning and extinction are thought to be related to
      the pathophysiology of anxiety disorders including obsessive-compulsive disorder
      (OCD). We have reported alterations of auditory P50 suppression in human fear
      conditioning and extinction in healthy control subjects (Kurayama et al., 2009).
      In the study, P50 suppression was impaired transiently in the course of fear
      acquisition and extinction. In this study, we investigated the changes of P50
      suppression with OCD patients in the course of the same experimental paradigm. 39
      patients with OCD and 21 healthy control subjects were recruited. In the
      acquisition phase of classical fear conditioning, 10 pairings of the conditioned
      stimulus (CS; the visual stimulus from a light-emitting diode) and the
      unconditioned stimulus (US; the electrical stimulus to the wrist) were
      administered, and in the extinction phase, 10 CS without US were administered.
      P50 auditory evoked potentials were measured as the first stimulus sound (S1) and
      the second stimulus sound (S2) in double-click paradigm with a 500 ms interval.
      P50 S2/S1 ratio was used to evaluate P50 suppression. The mean P50 S2/S1 ratio in
      patients with OCD significantly elevated from baseline level during the fear
      acquisition as that in healthy controls, but the elevated S2/S1 ratio did not
      recover to baseline level. The S2/S1 ratio in the extinction phase was
      significantly higher in the OCD patient group than in the healthy control group.
      In conclusion, our data suggested that P50 sensory gating in fear extinction was
      impaired in patients with OCD.

PMID- 20035818
TI  - Comparison of Silybum marianum (L.) Gaertn. with fluoxetine in the treatment of
      Obsessive-Compulsive Disorder.
AB  - Obsessive-Compulsive Disorder (OCD) is a common neuropsychiatric condition.
      Although a variety of pharmaceutical agents is available for the treatment of
      OCD, psychiatrists often find that many patients cannot tolerate the side effects
      of these medications; do not respond properly to the treatment; or the
      medications lose their effectiveness after a period of treatment. Herbal medicine
      can be a solution to some of these problems. In fact many herbs with psychotropic
      effects exist which can have fewer side effects. They can provide an alternative
      treatment or be used to enhance the effectiveness of conventional anti-obsessive
      and compulsive symptoms. Silybum marianum (L.) Gaertn. is a well-known medicinal
      plant with a long history of usage in Iran. This plant is reported to be safe on
      humans. Our objective in this study was to compare the efficacy of the extract of
      S.marianum (L.) with fluoxetine in the treatment of OCD. The study was an 8-week
      pilot double-blind randomized trial. Thirty five adult outpatients who met the
      DSM-IV-TR criteria for OCD based on the structured clinical interview
      participated in the trial. The minimum score of Yale-Brown Scale for OCD was 21
      for all patients. In this double-blind and randomized trial, patients were
      randomly assigned to receive either capsule of the extract (600 mg/day) or
      fluoxetine (30 mg/day) for 8 weeks. The results showed no significant difference
      between the extract and fluoxetine in the treatment of OCD. There was also no
      significant difference between the two groups in terms of observed side effects.

PMID- 20035819
TI  - Safety assessment of a novel ingredient for removable chewing gum.
AB  - Rev7 is an indigestible gum polymer used for the manufacturing of chewing gum. It
      allows for the formulation of chewing gum with low adhesion; thus can be readily
      removed from surfaces such as sidewalks, clothing, carpets and furniture. In a
      toxicological safety assessment, Rev7 was found to be non-mutagenic in the AMES
      assay. The highest concentration tested in a mouse lymphoma thymidine kinase
      locus gene mutation assay induced a slight but biologically relevant increase in
      mutations under non-metabolic activation conditions after 24h. Because of this
      finding, a mouse micronucleus assay was performed, and the test article was found
      to be negative for inducing chromosomal damage. A 28-day repeated oral toxicity
      study resulted in a NOAEL of 80,000 ppm; the highest concentration tested. Rev7
      was found to be free from contaminants such as heavy metals, monomers, and
      solvents. Lastly, Rev7 did not demonstrate skin-sensitizing properties in the
      murine local lymph node assay.

PMID- 20035820
TI  - Permethrin-induced morphological changes in oocytes of Rhipicephalus sanguineus
      (Acari: Ixodidae) semi-engorged females.
AB  - The permethrin, active ingredient of the Advantage(R) Max3--Bayer, has been
      widely used in the chemical control of ticks. These ectoparasites are one of the
      most important animal groups that cause serious damage to their hosts. This study
      evaluated the toxic effects of permethrin in oocytes of Rhipicephalus sanguineus
      semi-engorged females subjected to four treatments: group I (control--distilled
      water), group II (206 ppm of permethrin), group III (1031 ppm of permethrin) and
      group IV (2062 ppm of permethrin). Results demonstrated that permethrin is a
      potent chemical agent causing major structural changes in oocytes, such as
      emergence of large vacuolated cytoplasm regions, reducing the amount of yolk
      granules and decreasing the size of oocytes, culminating with cell death. As
      reported in the literature, these oocytes changes, besides affect the tick
      nervous system, also drastically reduce or prevent the reproduction process in
      females of R. sanguineus ticks subjected to this compound.

PMID- 20035821
TI  - A critique of prevailing approaches to nutrient risk analysis pertaining to food
      supplements with specific reference to the European Union.
AB  - In the European Union (EU), interest in risk analysis as applied to
      micronutrients is being stimulated by the increasing availability and marketing
      of food (dietary) supplements, functional and fortified foods. There is also
      strong inter-governmental interest in harmonizing methods regionally and
      globally. Various models are being evaluated in the EU for the purposes of
      developing Community-wide, mandatory maximum (and minimum) permitted levels, as
      required by EC Directive 2002/46/EC and Regulation (EC) No 1925/2006 on food
      supplements and fortified foods, respectively. This paper provides a scientific
      critique of models currently proposed in the EU and demonstrates weaknesses in
      both the risk assessment methods used to determine upper tolerable levels (ULs)
      as well as the risk management approaches being considered for the determination
      of maximum levels, particularly as applied to food supplements. Methods for
      ameliorating existing models are proposed here, including a proposal for using
      decision science as the underlying methodology in nutrient risk analysis. Risk
      management approaches based on more plausible scientific methods would avoid
      unnecessarily restrictive policy-based levels that would adversely impact
      consumer choice, while contributing to a 'better regulation' approach.
      Scientifically robust and rational methods of nutrient risk analysis are
      consistent with disease risk reduction, health management and consumer protection
      strategies.

PMID- 20035822
TI  - Cysticercosis and neurocysticercosis as pathogens affecting the nervous system.
AB  - Taenia solium cysticercosis is still a major cause of seizures around the world.
      Despite an extensive body of published literature on this topic, knowledge of the
      biology, immunology, pathophysiology, and treatment of this parasite remains
      largely incomplete. This review summarizes recent information on the biology,
      clinical manifestations, immunopathology treatment and control of this important
      and neglected zoonotic disease, with emphasis on areas where recent developments
      have changed traditional and established views.

PMID- 20035823
TI  - Abnormalities of the alphabeta T-cell receptor repertoire in advanced
      myelodysplastic syndrome.
AB  - OBJECTIVE: Analysis of the alphabeta T-cell receptor (TCR) repertoire in patients
      with myelodysplastic syndrome (MDS) using the technique of TCR beta-chain
      spectratyping has provided valuable insight into the pathophysiology of
      cytopenias in a subset of patients with this heterogeneous disorder. TCR beta
      chain spectratypes are complex data sets, however, and statistical tools for
      their comprehensive analysis are limited. The objective of the present work was
      to develop a method to enable quantitative evaluation and global comparison of
      spectratype data from different individuals and to study the prevalence of TCR
      beta repertoire abnormalities in MDS patients. MATERIALS AND METHODS: We
      developed a robust statistical method based on k-means clustering analysis, and
      applied this method to analysis of the alphabeta TCR repertoires in 50 MDS
      patients and 23 age-matched healthy controls. RESULTS: Cluster analysis
      identified a subset of 11 MDS patients with profoundly abnormal alphabeta TCR
      repertoires. This group of patients was characterized by advanced disease by
      International Prognostic Scoring System and World Health Organization criteria,
      increased expression of the Wilms' tumor-1 oncogene, increased bone marrow
      myeloblast count, and older age. CONCLUSIONS: We have developed a robust analytic
      algorithm that enables the comparison of alphabeta TCR repertoires between
      individuals and have shown that abnormal alphabeta TCR repertoire is a feature of
      a subset of patients with advanced MDS.

PMID- 20035824
TI  - Impact of CXCR4 inhibition on FLT3-ITD-positive human AML blasts.
AB  - OBJECTIVE: Internal tandem duplication (ITD) mutations of the FLT3 receptor are
      associated with a high incidence of relapse in acute myeloid leukemia (AML).
      Expression of the CXCR4 receptor in FLT3-ITD-positive AML is correlated with poor
      outcome, and inhibition of CXCR4 was shown to sensitize AML blasts toward
      chemotherapy. The aim of this study was to evaluate the impact of FLT3-ITD on
      cell proliferation and CXCR4-dependent migration in human hematopoietic
      progenitor cells and to investigate their response to CXCR4 inhibition. MATERIALS
      AND METHODS: We used primary blasts from patients with FLT3-ITD or FLT3 wild-type
      AML. In addition, human CD34(+) hematopoietic progenitor cells were transduced to
      >70% with retroviral vectors containing human FLT3-ITD. RESULTS: We found that
      FLT3-ITD transgene overexpressing human hematopoietic progenitor cells show
      strongly reduced migration toward stromal-derived factor-1 in vitro and display
      significantly reduced bone marrow homing in nonobese diabetic severe combined
      immunodeficient mice. Cocultivation of FLT3-ITD-positive AML blasts or
      hematopoietic progenitor cells on bone marrow stromal cells resulted in a strong
      proliferation advantage and increased early cobblestone area-forming cells
      compared to FLT3-wild-type AML blasts. Addition of the CXCR4 inhibitor AMD3100 to
      the coculture significantly reduced both cobblestone area-forming cells and
      proliferation of FLT3-ITD-positive cells, but did not affect FLT3-wild-type cells
      highlighting the critical interaction between CXCR4 and FLT3-ITD. CONCLUSION:
      CXCR4 inhibition to decrease cell proliferation and to control the leukemic
      burden may provide a novel therapeutic strategy in patients with advanced FLT3
      ITD-positive AML.

PMID- 20035825
TI  - Androgen receptor and androgen-dependent gene expression in lung.
AB  - The androgen receptor (AR) mediates the effects of male sex steroids. There are
      major sex differences in lung development and pathologies, including lung cancer.
      In this report, we show that Ar is mainly expressed in type II pneumocytes and
      the bronchial epithelium of murine lung and that androgen treatment increases AR
      protein levels in lung cells. Androgen administration altered significantly
      murine lung gene expression profiles; for example, by up-regulating transcripts
      involved in oxygen transport and down-regulating those in DNA repair and DNA
      recombination. Androgen exposure also affected the gene expression profile in a
      human lung adenocarcinoma-derived cell line, A549, by up- or down-regulating
      significantly some 200 transcripts, including down-regulation of genes involved
      in cell respiration. Dexamethasone treatment of A549 cells augmented expression
      of transcript sets that overlapped in part with those up-regulated by androgen in
      these cells. Moreover, a human lung cancer tissue array revealed that different
      lung cancer types are all AR-positive. Our results indicate that adult lung is an
      AR target tissue and suggest that AR plays a role in lung cancer biology.

PMID- 20035826
TI  - Metabolic regulation of ghrelin O-acyl transferase (GOAT) expression in the mouse
      hypothalamus, pituitary, and stomach.
AB  - Ghrelin acts as an endocrine link connecting physiological processes regulating
      food intake, body composition, growth, and energy balance. Ghrelin is the only
      peptide known to undergo octanoylation. The enzyme mediating this process,
      ghrelin O-acyltransferase (GOAT), is expressed in the gastrointestinal tract (GI;
      primary source of circulating ghrelin) as well as other tissues. The present
      study demonstrates that stomach GOAT mRNA levels correlate with circulating
      acylated-ghrelin levels in fasted and diet-induced obese mice. In addition, GOAT
      was found to be expressed in both the pituitary and hypothalamus (two target
      tissues of ghrelin's actions), and regulated in response to metabolic status.
      Using primary pituitary cell cultures as a model system to study the regulation
      of GOAT expression, we found that acylated-ghrelin, but not desacyl-ghrelin,
      increased GOAT expression. In addition, growth-hormone-releasing hormone (GHRH)
      and leptin increased, while somatostatin (SST) decreased GOAT expression. The
      physiologic relevance of these later results is supported by the observation that
      pituitary GOAT expression in mice lacking GHRH, SST and leptin showed opposite
      changes to those observed after in vitro treatment with the corresponding
      peptides. Therefore, it seems plausible that these hormones directly contribute
      to the regulation of pituitary GOAT. Interestingly, in all the models studied,
      pituitary GOAT expression paralleled changes in the expression of a dominant
      spliced-variant of ghrelin (In2-ghrelin) and therefore this transcript may be a
      primary substrate for pituitary GOAT. Collectively, these observations support
      the notion that the GI tract is not the only source of acylated-ghrelin, but in
      fact locally produced des-acylated-ghrelin could be converted to acylated-ghrelin
      within target tissues by locally active GOAT, to mediate its tissue-specific
      effects.

PMID- 20035827
TI  - Type 2 immune-inducing helminth vaccination maintains protective efficacy in the
      setting of repeated parasite exposures.
AB  - Animal studies have demonstrated that helminth vaccines which induce type 2
      immune responses can be protective. To date, however, such vaccines have not been
      tested against repeated parasite challenges. Since repeated antigenic challenge
      of patients with allergic disease results in immunologic tolerance, we
      hypothesized that a helminth vaccine which induces type 2 immune responses may
      lose its protective efficacy in the setting of repeated parasite exposures
      (RPEs). To test this hypothesis, we examined whether RPEs induce immunological
      tolerance and reduce the effectiveness of a type 2 immune-inducing vaccine.
      BALB/c mice vaccinated against Litomosoides sigmodontis, a filarial nematode of
      rodents, were repeatedly exposed to irradiated larvae for 2 or 8 weeks or to non
      irradiated infectious larvae for three months. Vaccination-induced parasite
      specific IgE levels, parasite antigen-driven basophil interleukin 4 (IL-4)
      release, and Th2 skewing of the cellular immune response remained stable in the
      face of RPEs. Furthermore, RPEs in vaccinated mice did not augment
      immunoregulatory responses, as parasite antigen-driven cellular proliferation,
      production of IL-10, and frequencies of CD4(+)CD25(+)FoxP3(+) regulatory T-cells
      were not altered by RPEs. Challenge infections with infectious L3-stage larvae
      resulted in lower worm burdens in vaccinated mice given RPEs than in vaccinated
      controls. These results demonstrate that vaccines which induce type 2 immune
      responses can maintain their efficacy in the setting of repeated parasite
      exposures.

PMID- 20035828
TI  - A detailed characterisation of the distribution and presentation of DNA vaccine
      encoded antigen.
AB  - The association between plasmid DNA distribution, the amount of Ag produced, Ag
      persistence and the identity and localisation of cells presenting DNA-encoded Ag
      all have important consequences for both quantitative and qualitative aspects of
      T cell responses induced by DNA vaccines. Using a variety of approaches to detect
      and quantify the uptake of injected DNA, and the production and presentation of
      DNA-encoded antigen, we report that injected DNA vaccines rapidly enter the
      peripheral blood from the injection site and also reach muscle-draining lymph
      nodes directly as free DNA. 24h after plasmid injection, MHCII(+)CD11b(+)B220(
      )CD11c(low/-) cells in the draining and distal LNs and spleen contain pDNA.
      Interestingly, we also observed pDNA(+)MHCII(low/-)CD11b(+) within the bone
      marrow. Concomitantly, we detected Ag-containing/expressing cells at both the
      injection site and in draining lymph nodes. Three days after plasmid injection we
      detected rare pMHC(+)CD11c(+) cells within secondary lymphoid tissue and
      simultaneously observed Ag-specific CD4(+) T cell accumulation and blastogenesis
      in these tissues. Our results show that the events that determine the induction
      of DNA vaccine immune responses occur within days of DNA injection and that the
      response becomes systemic very rapidly, possibly with involvement from resident
      BM cells.

PMID- 20035829
TI  - Comparison of the antiepileptic properties of transmeningeally delivered
      muscimol, lidocaine, midazolam, pentobarbital and GABA, in rats.
AB  - This study compared the potencies of epidurally delivered muscimol, lidocaine,
      midazolam, pentobarbital and gamma-aminobutyric acid (GABA) to prevent focal
      neocortical seizures induced by locally applied acetylcholine (Ach), in rats
      (n=5). An epidural cup was chronically implanted over the right somatosensory
      cortex in each animal, with epidural EEG electrodes placed posterior to the edge
      of the cup. After recovery, either artificial cerebrospinal fluid (ACSF; control
      solution) or one of the five drugs was delivered into epidural cup, followed by
      Ach administration into the cup to induce seizures. EEG seizure duration ratio
      was calculated for each drug delivery/seizure induction session to determine the
      potency of ACSF and the drugs to prevent the focal Ach-seizures. The
      concentration of all examined drug solutions was 1.0mM. ACSF, lidocaine,
      midazolam, pentobarbital and GABA all failed to prevent the Ach-induced
      neocortical EEG seizures, yielding EEG seizure duration ratios ranging from 0.41
      to 0.80. In contrast, muscimol pretreatment fully prevented the development of
      ictal EEG in all animals. These results suggest that when used at low
      concentration muscimol was the best of the five drugs for transmeningeal
      pharmacotherapy trials for focal neocortical epilepsy.

PMID- 20035830
TI  - Functional neuroimaging of duration discrimination on two different time scales.
AB  - Analyses of neural mechanisms of duration processing are essential for the
      understanding of psychological phenomena which evolve in time. Different
      mechanisms are presumably responsible for the processing of shorter (below 500
      ms) and longer (above 500 ms) events but have not yet been a subject of an
      investigation with functional magnetic resonance imaging (fMRI). In the present
      study, we show a greater involvement of several brain regions - including right
      hemispheric midline structures and left-hemispheric lateral regions - in the
      processing of visual stimuli of shorter as compared to longer duration. We
      propose a greater involvement of lower-level cognitive mechanisms in the
      processing of shorter events as opposed to higher-level mechanisms of cognitive
      control involved in longer events.

PMID- 20035831
TI  - TNF-alpha receptor 1 deficiency reduces antigen-presenting capacity of Schwann
      cells and ameliorates experimental autoimmune neuritis in mice.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic pro-inflammatory
      cytokine with potentially neurodestructive effects and plays a pivotal role in
      autoimmune demyelinating disease. To address the role of TNF-alpha in the
      pathogenesis of experimental autoimmune neuritis (EAN), the current study
      investigated the antigen-presenting capacity of Schwann cells (SCs) in EAN
      induced by P0 protein peptide 106-125 in TNF-alpha receptor 1 deficient (TNFR1(-/
      )) mice. The antigen-presenting capacity of SCs was assessed by the expression of
      MHC class II (MHCII), CD40, CD80 and CD86 molecules on activated SCs as well as
      by induction of T cell proliferation in co-cultures of P0 protein peptide 106-125
      specific T cells with activated SCs. In addition, the expression of inducible
      nitric oxide synthase (iNOS) was measured in activated SCs by flow cytometry.
      TNFR1(-/-) EAN mice developed significantly delayed and reduced clinical signs of
      EAN compared to wild type EAN mice. In parallel, the expression of MHCII, CD80
      and iNOS on SCs were decreased in TNFR1(-/-) mice compared to wild type mice.
      Likewise, proliferation of P0 protein peptide 106-125 specific T cells simulated
      by activated SCs of TNFR1(-/-) EAN mice was lower than that of wild type EAN
      mice. Our data suggest that TNF-alpha may exert pro-inflammatory effects in EAN
      via TNFR1 by up-regulating the antigen-presenting function and iNOS production of
      SCs.

PMID- 20035832
TI  - Prenatal stress alters presynaptic marker proteins in the hippocampus of rat
      pups.
AB  - Exposure to stress during critical periods of an organism's maturation can result
      in permanent behavioral changes and induced hyper-responsive to aversive stimuli
      as adult. Hippocampus is a plastic and vulnerable brain structure that is
      susceptible to damage during aging and repeated stress. The present study
      examines the effect of maternal restraint stress on the level of GAP-43, pGAP-43
      and synaptophysin in the hippocampus of rat pups. Prenatal stress (PS) causes a
      significant increase of GAP-43 and pGAP-43 (p<or=0.001) in the pup's hippocampus
      during postnatal days 7 and 14, but not at later ages. Up-regulation of GAP-43
      and pGAP-43 may alter the pattern of axonal growth and synapses' formation in the
      pup's brain since the first two postnatal weeks are correlated with peak period
      of synaptogenesis in the rat brain. We also examined the level of synaptophysin,
      a synaptic vesicle membrane protein, in the pup's brain. Our finding revealed
      that, PS causes a significant decrease of synaptophysin in the pup's hippocampus
      as compared to control (p<or=0.001). These changes are due to the direct effects
      of maternal stress hormone since repeated injection with corticosterone (CORT, 40
      mg/kg) to pregnant rat during gestation days (GDs) 14-21 also gave the same
      results. Abnormal axonal sprouting and reorganization together with the
      alterations in synaptic vesicle membrane protein during the critical period of
      synaptogenesis may lead to a defect in synapse formation and axonal pruning in
      the hippocampus. These changes may be associated with stress-induced impairment
      of hippocampal function that occurs in later life of the offspring.

PMID- 20035833
TI  - Contribution of gamma-secretase to calcium-mediated cell death.
AB  - Presenilins are the catalytic subunit of the large gamma-secretase complex, that
      promotes intramembranous proteolysis of the beta-amyloid precursor protein (APP),
      resulting in the production of beta-amyloid (A beta). Mutant presenilin causes
      early-onset familial Alzheimer's disease (FAD), is related to abnormal Ca(2+)
      signaling, and render cells vulnerable to cell death. In the present study, we
      demonstrated that Ca(2+)-mediated cell death is functionally associated with
      gamma-secretase activity. We found that gamma-secretase activity was elevated
      during Ca(2+)-mediated cell death. Using selective gamma-secretase inhibitors, we
      examined the role of gamma-secretase in cell death triggered by increased
      intracellular Ca(2+). Indeed, treatment with the selective gamma-secretase
      inhibitors, compound E, DAPT, or L-685.458 significantly decreased Ca(2+)
      triggered cell death with that of the controls, but did not affect staurosporin
      or tunicamycin-mediated cell death. These results implicate the role of gamma
      secretase activity in Ca(2+)-mediated cell death.

PMID- 20035834
TI  - Hypnotizability-related EEG alpha and theta activities during visual and
      somesthetic imageries.
AB  - Hypnotizability is a cognitive multidimensional trait that involves peculiar
      imagery characteristics. Subjects with high- (Highs) and low (Lows)
      susceptibilities to hypnosis have shown different levels of skill at visual and
      somesthetic-guided imageries performed during upright stance. The aim of this
      experiment is to study the modulation of the EEG alpha and theta band amplitude
      during guided visual and somesthetic imageries in Highs and Lows, as these
      rhythms are responsive to the cognitive activities involved in mental imagery.
      Our results show that, at variance with standing subjects, subjects in both
      groups in a semi-reclined position report higher vividness and lower effort for
      visual than for somesthetic imagery. EEG patterns however are different between
      the two groups. Highs exhibit a more widespread alpha desynchronization and
      slightly different EEG patterns during visual and somesthetic imageries, while
      Lows show segregated alpha- and theta-desynchronization, without any difference
      between the tasks. Our results indicate that different, hypnotizability-related
      cognitive strategies, that are revealed by differences in EEG modulation, are
      responsible for the similar subjective experience associated with visual and
      somesthetic imageries in Highs and Lows. In addition, in both groups higher order
      mental representation of different sensory modalities might be subserved by a
      unique integrated neural network.

PMID- 20035835
TI  - Influence of motor learning on utilizing path redundancy.
AB  - We examined the role of motor learning in influencing the utilization of path
      redundancy in an interception task. Participants used a pen on a digitizing
      tablet with the goal of moving to intercept a stationary target shown on a
      computer screen. Concurrent visual feedback of the cursor and knowledge of
      results were provided. The changes in spatial variability after extended practice
      and the correlations between spatial locations on the path were consistent with
      the view that path redundancy was utilized. However, paths also became less
      variable with practice, indicating that less of the solution space was utilized.
      There was also a sequential relation in the movement paths from trial to trial
      with a tendency to use more similar movement paths on successive trials. These
      results show that models that account for both redundancy and invariance may be
      better able to capture the changes in variability with learning. Further, the
      sequential dependence in the paths suggests that the exploration of redundant
      solutions is a systematic search process.

PMID- 20035836
TI  - Adaptations in medial prefrontal cortex function associated with amphetamine
      induced behavioral sensitization.
AB  - Neuroadaptations in the prefrontal cortex (PFC) are hypothesized to play an
      important role in the behavioral changes associated with repeated psychostimulant
      exposure, but there are few published studies that measure neuronal activity
      during the development and expression of sensitization. To address this, we
      recorded single neuron activity in the medial PFC (mPFC) of male rats that were
      exposed for 5 days to saline or amphetamine (AMPH; 1.0 mg/kg i.p.) and then given
      saline or AMPH challenges following a three-day withdrawal. We found that rats
      exposed to AMPH developed locomotor sensitization to the drug that emerged on the
      fifth treatment session and became statistically significant at AMPH challenge.
      This was associated with no change in baseline (i.e., pre-injection) activity of
      mPFC neurons across the treatment or challenge sessions. Following the first AMPH
      injection, mPFC neurons responded primarily with reductions in firing, with the
      overall pattern and magnitude of responses remaining largely similar following
      repeated treatment. The exception was in the minority of cells that respond to
      AMPH with increases in firing rate. In this population, the magnitude of
      excitations peaked during the fifth AMPH exposure and was still relatively
      elevated at the AMPH challenge. Furthermore, these units increased firing during
      a saline challenge that was given to assess associative conditioning. These
      results suggest that AMPH-induced adaptations in mPFC function are not as
      apparent as AMPH-induced adaptations in behavior. When mPFC adaptations do occur,
      they appear limited to the population of neurons that increase their firing in
      response to AMPH.

PMID- 20035837
TI  - Lipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor
      cells and impede their development.
AB  - Damage to oligodendrocyte (OL) progenitor cells (OPCs) and hypomyelination are
      two hallmark features of periventricular leukomalacia (PVL), the most common form
      of brain damage in premature infants. Clinical and animal studies have linked the
      incidence of PVL to maternal infection/inflammation, and activated microglia have
      been proposed to play a central role. However, the precise mechanism of how
      activated microglia adversely affects the survival and development of OPCs is
      still not clear. Here we demonstrate that lipopolysaccharide (LPS)-activated
      microglia are deleterious to OPCs, that is, impeding OL lineage progression,
      reducing the production of myelin basic protein (MBP), and mediating OPC death.
      We further demonstrate that LPS-activated microglia mediate OPC death by two
      distinct mechanisms in a time-dependent manner. The early phase of cell damage
      occurs within 24 h after LPS treatment, which is mediated by nitric oxide (NO)
      dependent oxidative damage and is prevented by N(G)-nitro-l-arginine methyl ester
      (l-NAME), a general inhibitor of nitric oxide synthase. The delayed cell death is
      evident at 48 h after LPS treatment, is mediated by cytokines, and is prevented
      by blocking the activity of tumor necrosis factor-alpha (TNF-alpha) and pro-nerve
      growth factor (proNGF), but not by l-NAME. Furthermore, microglia-derived insulin
      like growth factor-1 (IGF-1) and ciliary neurotrophic factor (CNTF) were
      significantly suppressed by LPS, and exogenous IGF-1 and CNTF synergistically
      protected OLs from death induced by LPS-treated microglia conditioned medium,
      indicating that a deficiency in trophic support may also be involved in OL death.
      Our finding that LPS-activated microglia not only induce two waves of cell death
      but also greatly impair OL development may shed some light on the mechanisms
      underlying selective white matter damage and hypomyelination in PVL.

PMID- 20035838
TI  - Involvement of NTS2 receptors in stress-induced analgesia.
AB  - Stress activates multiple neural systems that suppress pain sensation. This
      adaptive phenomenon referred as stress-induced analgesia (SIA) is mediated by the
      activation of endogenous pain inhibitory systems. Both opioid and non-opioid
      forms of SIA have been elicited in rodents according to stressor parameters and
      duration. There is accumulating evidence that the endogenous neurotensin (NT)
      system plays an important role in SIA. Especially, NT-deficient mice were shown
      to exhibit reduced SIA following water avoidance or restraint stress. Since
      central NT produces naloxone-insensitive analgesic effects by acting on spinal
      and supraspinal NTS2 receptors, we hypothesized that NT might mediate non-opioid
      SIA through NTS2 activation. Here, we evaluated the influence of an opioid
      independent severe stress produced by a cold-water swim for 3 min at 15 degrees C
      on rodent offspring's pain perception. Our results demonstrated that mice lacking
      NTS2 exhibit significantly reduced SIA following cold-water swim stress. Indeed,
      NTS2 knockout mice submitted to both acute (plantar test) and tonic (formalin
      test) pain stimuli show a greater sensitivity to pain in comparison to wild-type
      littermates. Accordingly, pretreatment with the NT receptor antagonist SR142948A
      results in a hyperalgesic response to stress induced by cold-water swim.
      Endogenous NT regulates hypothalamic-pituitary-adrenal axis activity in stress
      condition by increasing corticosterone plasma levels. Accordingly, the plasma
      levels of corticosterone measured by radioimmunoassay are significantly reduced
      in non-stressed and stressed NTS2-deficient mice in comparison with wild-type
      mice. To further investigate the site of action of NT in mediating SIA, we
      microinjected NTS2 agonists in lumbar spinal cord and quantified post-stress
      sensitivity to pain in rats using the plantar test. Exogenously administered NTS2
      analogs, JMV-431, beta-lactotensin and NT69L markedly enhance the magnitude and
      duration of stress antinociception in both 25- and 60-day-old rats. In sum, by
      using genetic and pharmacological approaches, we demonstrated here that NTS2
      receptors mediate non-opioid SIA. Our results also revealed that the release of
      endogenous NT in response to stress requires the presence of NTS2 to stimulate
      corticotropin-releasing factor (CRF)-induced elevation of plasma corticosterone,
      and that NTS2 receptors localized at the lumbar spinal cord participate to the
      disinhibition of descending pain control pathways. Therefore, these data
      highlight the significance of NTS2 as a novel target for the treatment of pain
      and stress-related disorders.

PMID- 20035839
TI  - Differential regulation of synapsin phosphorylation by monocular deprivation in
      juveniles and adults.
AB  - The rodent visual cortex retains significant ocular dominance plasticity beyond
      the traditional postnatal critical period. However, the intracellular mechanisms
      that underlie the cortical response to monocular deprivation are predicted to be
      different in juveniles and adults. Here we show monocular deprivation in adult,
      but not juvenile rats, induced an increase in the phosphorylation of the
      prominent presynaptic effecter protein synapsin at two key sites known to
      regulate synapsin function. Monocular deprivation in adults induced an increase
      in synapsin phosphorylation at the PKA consensus site (site 1) and the CaMKII
      consensus site (site 3) in the visual cortex ipsilateral to the deprived eye,
      which is dominated by non-deprived eye input. The increase in synapsin
      phosphorylation was observed in total cortical homogenate, but not
      synaptoneurosomes, suggesting that the pool of synapsin targeted by monocular
      deprivation in adults does not co-fractionate with excitatory synapses.
      Phosphorylation of sites 1 and 3 stimulates the release of synaptic vesicles from
      a reserve pool and increases in the probability of evoked neurotransmitter
      release, which may contribute to the strengthening of the non-deprived input
      characteristic of ocular dominance plasticity in adults.

PMID- 20035840
TI  - Poly (ADP-ribose) polymerase-1 initiated neuronal cell death pathway--do
      androgens matter?
AB  - Activation of poly (ADP-ribose) polymerases (PARP) contributes to ischemic damage
      by causing neuronal nicotinamide adenine dinucleotide (NAD(+)) depletion, release
      of apoptosis-inducing factor and consequent caspase-independent cell death. PARP
      mediated cell death is sexually dimorphic, participating in ischemic damage in
      the male brain, but not the female brain. We tested the hypothesis that androgen
      signaling is required for this male-specific neuronal cell death pathway. We
      observed smaller damage following focal cerebral ischemia (MCAO) in male PARP-1
      knockout mice compared to wild type (WT) as well as decreased damage in male mice
      treated with the PARP inhibitor PJ34. Protection from ischemic damage provided by
      PJ-34 in WT mice is lost after removal of testicular androgens (CAST) and rescued
      by androgen replacement. CAST PARP-1 KO mice exhibit increased damage compared to
      intact male KO mice, an effect reversed by androgen replacement in an androgen
      receptor-dependent manner. Lastly, we observed that ischemia causes an increase
      in PARP-1 expression that is diminished in the absence of testicular androgens.
      Our data indicate that PARP-mediated neuronal cell death in the male brain
      requires intact androgen-androgen receptor signaling.

PMID- 20035841
TI  - Developmental emergence of reelin deficits in the prefrontal cortex of Wistar
      rats reared in social isolation.
AB  - As the pathophysiological mechanism(s) of many neuropsychiatric disorders relate
      to GABAergic interneuron structure and function, we employed isolation rearing of
      Wistar rats as a model to correlate developmental emergence of cognitive deficits
      with the expression of reelin-producing interneurons in the medial prefrontal
      cortex (PFC). Prepulse inhibition deficits emerged at postnatal day 60 and
      persisted into adulthood. Paralleling the emergence of these neurobehavioural
      deficits was an increase in reelin production and reelin-immunopositive cells in
      layer I of the PFC and this later became significantly reduced at postnatal day
      80. Cells expressing reelin immunoreactivity in a horizontal orientation were
      mainly located to the upper regions of layer I whereas those with a vertical
      orientation, whose arbors extend into cortical layers II and III, were more
      numerous in the lower regions of layer I and became significantly dysregulated
      during postnatal development. No behavioural deficits or altered reelin
      expression was observed at postnatal days 30 or 40. Developmental emergence of
      neurobehavioural and reelin deficits in isolation reared animals is proposed to
      reflect maladaptive wiring within the medial prefrontal cortex during a critical
      maturation period of this circuitry.

PMID- 20035842
TI  - Cholinergic modulation of non-N-methyl-D-aspartic acid glutamatergic transmission
      in the chick ventral lateral geniculate nucleus.
AB  - Neurotransmission between glutamatergic terminals of retinal ganglion cells and
      principal neurons of the ventral lateral geniculate nucleus (LGNv) was examined
      with patch clamp recordings in chick brain slices during electrical stimulation
      of the optic tract. Since muscarinic and nicotinic receptors are present in high
      densities in LGNv, the present study examined possible roles of both receptors in
      modulating retinogeniculate transmission. During whole-cell recordings from LGNv
      neurons, acetylcholine (ACh, 100 microM) caused an initial increase in amplitudes
      of optic tract-evoked non-N-methyl-D-aspartic acid (NMDA) glutamatergic
      postsynaptic currents (PSCs). This increase was unchanged when 1 microM atropine
      was present, indicating that this initial enhancement of PSCs was due entirely to
      activation of nicotinic receptors. However, during washout of ACh the amplitudes
      of evoked PSCs became significantly decreased by 40.4+/-5.0% for several minutes
      before recovering to their original amplitudes, an effect blocked by 1 microM
      atropine. Exogenously applied muscarine (10 microM) markedly depressed optic
      tract-evoked PSCs, and this decrease in amplitude was blocked by atropine. In a
      second set of experiments, we examined effects of releasing endogenous ACh prior
      to optic tract stimulation. This was accomplished by stimulation of the lateral
      portion of LGNv via a separate conditioning electrode. Following a brief train of
      low intensity conditioning stimuli, non-NMDA glutamatergic PSCs evoked by optic
      tract stimulation were potentiated. However, at higher conditioning stimulus
      intensities the PSCs were markedly decreased compared with control, and this
      decrease was partially blocked by atropine (1 microM). Neither ACh nor muscarine
      altered amplitudes of PSCs elicited by exogenously applied glutamate. Muscarine
      significantly reduced the frequency but not the amplitudes of miniature PSCs,
      consistent with a presynaptic location for muscarinic receptors mediating these
      effects. Thus while activation of nicotinic receptors potentiates
      retinogeniculate transmission, activation of muscarinic receptors mediates
      depression of transmission, demonstrating a complex cholinergic modulation of
      sensory information in LGNv.

PMID- 20035843
TI  - Rhesus monkeys (Macaca mulatta) show robust primacy and recency in memory for
      lists from small, but not large, image sets.
AB  - The combination of primacy and recency produces a U-shaped serial position curve
      typical of memory for lists. In humans, primacy is often thought to result from
      rehearsal, but there is little evidence for rehearsal in nonhumans. To further
      evaluate the possibility that rehearsal contributes to primacy in monkeys, we
      compared memory for lists of familiar stimuli (which may be easier to rehearse)
      to memory for unfamiliar stimuli (which are likely difficult to rehearse). Six
      rhesus monkeys saw lists of five images drawn from either large, medium, or small
      image sets. After presentation of each list, memory for one item was assessed
      using a serial probe recognition test. Across four experiments, we found robust
      primacy and recency with lists drawn from small and medium, but not large, image
      sets. This finding is consistent with the idea that familiar items are easier to
      rehearse and that rehearsal contributes to primacy, warranting further study of
      the possibility of rehearsal in monkeys. However, alternative interpretations are
      also viable and are discussed.

PMID- 20035844
TI  - Within-session changes in licking as a function of sucrose concentration in
      common marmosets.
AB  - Common marmosets (Callithrix jacchus) were allowed to lick sucrose solutions
      freely in 30-min sessions. We examined how the rate of licking changed in the
      course of a session and how the pattern of changes was affected by different
      concentrations (1%, 5%, and 25%) of solutions. The results showed that licking
      rates decreased monotonically regardless of the concentrations and that the
      decreasing patterns could be reasonably explained by exponential functions. The
      rates of decrease were slowest for the 5% solution and fastest for the 1%
      solution. The linear relation between the number of licks in a short interval and
      the cumulative number of licks before that interval, which was suggested by
      Aoyama (1996), did not always hold. The cumulative records of licking for
      individual sessions revealed that a break-and-run pattern of licking sometimes
      dominated after a licking rate slowed down, and that this pattern could disturb
      the linear relation.

PMID- 20035845
TI  - Evolutionary relatedness of mackerels of the genus Scomber based on complete
      mitochondrial genomes: strong support to the recognition of Atlantic Scomber
      colias and Pacific Scomber japonicus as distinct species.
AB  - Mackerels of the genus Scomber are commercially important species, but their
      taxonomic status is still controversial. Although previous phylogenetic data
      support the recognition of Atlantic Scomber colias and Pacific Scomber japonicus
      as separate species, it is only based on the analysis of partial mitochondrial
      and nuclear DNA sequences. In an attempt to shed light on this relevant issue, we
      have determined the complete mitochondrial DNA sequence of S. colias, S.
      japonicus, and Scomber australasicus. The total length of the mitogenomes was
      16,568 bp for S. colias and 16,570 bp for both S. japonicus and S. australasicus.
      All mitogenomes had a gene content (13 protein-coding, 2 rRNAs, and 22 tRNAs) and
      organization similar to that observed in Scomber scombrus and most other
      vertebrates. The major noncoding region (control region) ranged between 865 and
      866 bp in length and showed the typical conserved blocks. Phylogenetic analyses
      revealed a monophyletic origin of Scomber species with regard to other scombrid
      fish. The major finding of this study is that S. colias and S. japonicus were
      significantly grouped in distinct lineages within Scomber cluster, which
      phylogenetically constitutes evidence that they may be considered as separate
      species. Additionally, molecular data here presented provide a useful tool for
      evolutionary as well as population genetic studies.

PMID- 20035846
TI  - Species-specific activation of nuclear receptors correlates with the response of
      liver drug metabolizing enzymes to EMD 392949 in vitro.
AB  - We previously reported on the species-specific effects on drug metabolizing
      enzymes (DME), in particular cytochrome P450-dependent monooxygenases (P450s), by
      the drug development candidate EMD 392949 (EMD) in vitro and in vivo. Induction
      of P450s occurs via activation of specific transcription factors such as the
      arylhydrocarbon receptor (AhR) and the nuclear xenobiotic receptors (NXRs). We
      analyzed whether the reported species-specific P450 induction by EMD could be
      related to a specific activation of the CYP1A regulator AhR and the CYP3A
      regulator pregnane X receptor (PXR) in human and rat cell lines. The human HepG2
      and rat H4IIE cell lines exhibited inducibility of CYP1A and 3A and expressed
      functional AhR as well as PXR. CYP3A was induced by EMD in human HepG2 cells
      exceeding the level induced by rifampicin, but was not induced in rat H4IIE
      cells. Regulation of P450s was not related to expression levels of their
      respective transcription factor, but EMD treatment resulted in a significant
      reporter gene activation in xenobiotic response enhancer module (XREM)
      transfected HepG2 but not H4IIE cells indicating activation of human but not rat
      PXR. In summary, we showed that the P450 inducing properties of EMD were
      perfectly reflected by its ability to activate AhR or PXR in a species-specific
      manner. These findings support the tight correlation of species-specific nuclear
      receptor activation with P450 induction and foster the use of nuclear receptor
      activation as a complementary screen to identify cytochrome P450 inducers.

PMID- 20035847
TI  - Acrylamide induces cell death in neural progenitor cells and impairs hippocampal
      neurogenesis.
AB  - Acrylamide (ACR) is a well-known neurotoxin in mammalian species that causes
      neuropathy characterized by ataxia and skeletal muscle weakness. Therefore, ACR
      mediated axon damage in the central and peripheral nervous systems is considered
      to be central-peripheral axonopathy. However, the molecular mechanisms underlying
      ACR's toxicity to neural progenitor cells are unknown. This study investigated
      the adverse effects of ACR on mouse multipotent neural progenitor cells and adult
      hippocampal neurogenesis. ACR significantly reduced the proliferation of neural
      progenitor cells, and high ACR concentrations induced apoptotic and necrotic cell
      death. We found that elevated intracellular levels of reactive oxygen species
      were involved in ACR-mediated cytotoxicity. Interestingly, the administration of
      ACR to young mice resulted in a significant decrease in the number of newly
      generated cells in the dentate gyrus of the hippocampus, suggesting an impairment
      of adult neurogenesis. These results suggest that ACR's deleterious effects on
      the central nervous system are due to the death of neural progenitor cells and
      impaired adult neurogenesis.

PMID- 20035848
TI  - Gene-carried chitosan-linked-PEI induced high gene transfection efficiency with
      low toxicity and significant tumor-suppressive activity.
AB  - PEI and chitosan are considered to be promising non-viral gene delivery vectors.
      To improve the transfection efficiency of chitosan, we linked chitosan with
      polyethylenimine (PEI, Mw=1.8 kDa) by 1,1'-carbonyldiimidazole to form a complex.
      The composition, particle size, as well as the zeta potential of this chitosan
      linked-PEI (CP) complex were measured. And the DNA binding ability, cytotoxicity,
      and gene transfection efficiency of CP complex were also investigated in cancer
      cells. In HepG2, A549 and HeLa cells, CP complex exhibited lower cytotoxicity as
      compared with PEI25KDa (Mw=25 kDa), a positive control proved to be an efficient
      gene transfection polymer. Likewise, it showed good transfection efficiency in
      these cancer cell lines. Specifically, the long-term transfection efficiency of
      CP was higher than PEI25KDa as demonstrated by the in vitro cancer cell model.
      The confocal laser scanning microscopy data showed the time for CP to enter the
      nucleus was 4h, which was longer than that of PEI25KDa but shorter than that of
      chitosan. Furthermore, CP complexes were used as a gene carrier to deliver the
      CCL22 gene into H22 cells. When these gene-altered cells were inoculated in mice,
      the tumor growth rate was significantly decreased, indicating the CP copolymer
      was a promising vector for the therapeutic gene delivery.

PMID- 20035849
TI  - Measurement and prediction of solubilities of active pharmaceutical ingredients.
AB  - Solubilities of 2-acetoxy benzoic acid (aspirin), N-acetyl-p-aminophenol
      (paracetamol) and 2-(p-isobutylphenyl)propionic acid (ibuprofen) have been
      measured in various solvents and compared with published and predicted data. For
      the prediction besides the two group contribution models UNIFAC and modified
      UNIFAC (Dortmund) the quantum chemical approach COSMO-RS (Ol) was used.
      Additionally melting temperatures and heats of fusion for 2-acetoxy benzoic acid,
      N-acetyl-p-aminophenol and 2-(p-isobutylphenyl)propionic acid required for the
      calculations have been determined by differential scanning calorimetry.

PMID- 20035850
TI  - Novel pH-sensitive microgels prepared using salt bridge.
AB  - pH-sensitive microgels were prepared by crosslinking carboxymethylcellulose (CMC)
      and polymeric beta-cyclodextrin (PbetaCD) using (2-hydroxyethyl)trimethylammonium
      chloride benzoate (TMACB) as a crosslinker. PbetaCD was prepared by reacting
      epichlorohydrin and beta-CD in an aqueous phase (NaOH solution, 30% (w/w)). TMACB
      will interact with CMC by an electrostatic interaction and it will also interact
      with PbetaCD by a hydrophobic interaction. The size of microgel was tens of
      nanometers to several micrometers. The degree of calcein release in 24h from the
      microgels was as low as 23% at pH 8.0. The degree of release at pH 3.0 was almost
      100%. The carboxyl groups of CMC will lose their charge in an acidic condition
      and they would lose their ability to form salt bridges with TMACB, leading to the
      disintegration of microgels. The degree of release at pH 11, about 47%, was less
      than the value at pH 3.0 but it was greater than the value at pH 8.0. The CMC
      will be strongly electrostatically charged in the alkali condition, so the
      microgels would swell due to the electrostatic repulsion among CMC molecules,
      which could promote the release of their contents.

PMID- 20035851
TI  - Multivariate optimization of formulation and process variables influencing
      physico-mechanical characteristics of site-specific release isoniazid pellets.
AB  - In the present study, isoniazid was formulated as site-specific release pellets
      with high drug loading (65%, w/w) using extrusion-spheronization followed by
      aqueous coating of Sureteric (35% weight gain). A statistical experimental
      strategy was developed to optimize simultaneously the effect of the two
      formulation variables and one process variable on the critical physico-mechanical
      properties of the core pellets of isoniazid. Amount of granulating fluid and
      amount of binder were selected as formulation variables and spheronization speed
      as a process variable. A 2(3) full factorial experimental design was employed for
      the present study. Pellets were characterized for physico-mechanical properties
      viz. usable yield, pellet size, pellips, porosity, abrasion resistance,
      mechanical crushing force, residual moisture and dissolution efficiency.
      Graphical and mathematical analysis of the results allowed the identification and
      quantification of the formulation and process variables active on the selected
      responses. A polynomial equation fitted to the data was used to predict the
      responses in the optimal region. The optimum formulation and process parameters
      were found to be 44.24% (w/w) of granulating fluid, 2.13% (w/w) of binder and
      spheronization speed of 1000rpm. Optimized formulation showed usable yield
      84.95%, particle size 1021.32microm, pellips 0.945, porosity 46.11%, and abrasion
      resistance 0.485%. However, mechanical crushing force, residual moisture and
      dissolution efficiency were not significantly affected by the selected
      independent variables. These results demonstrate the importance of, amount of
      water, binder and spheronization speed, on physico-mechanical characteristics of
      the isoniazid core pellets with high drug loading.

PMID- 20035852
TI  - In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract
      of the leaves of Piper sarmentosum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum (Piperaceae) is a medicinal
      plant traditionally used by the Malays to treat headaches, toothaches, coughs,
      asthma and fever. AIM OF THE STUDY: In order to establish the pharmacological
      properties of the leaf of this plant, studies were performed on anti-nociceptive
      and anti-inflammatory activities. MATERIALS AND METHODS: The aqueous extract of
      Piper sarmentosum (AEPS) was prepared in the doses of 30, 100 and 300 mg/kg. Anti
      nociceptive activity of AEPS was evaluated by abdominal constriction and hot
      plate tests. AEPS was also pre-challenged with 5mg/kg naloxone to determine the
      involvement of opioid receptors. Anti-inflammatory activity was evaluated using
      carrageenan-induced paw edema assay. RESULTS: Subcutaneous administration of AEPS
      exhibited anti-nociceptive activity (P<0.05) in a dose-dependent manner in the
      abdominal constriction and hot-plate tests. Pre-treatment with naloxone
      completely (P<0.05) diminished the extract anti-nociceptive activity in both
      tests. The AEPS, at all doses used, exerted significant (P<0.05) anti
      inflammatory activity in a dose-dependent manner. CONCLUSIONS: The AEPS exhibits
      opioid-mediated anti-nociceptive activity at the peripheral and central levels,
      as well as anti-inflammatory activity, which confirmed the traditional uses of
      the plant in the treatment of pain- and inflammatory-related ailments.

PMID- 20035853
TI  - Antiplasmodial and cytotoxic activities of Rwandan medicinal plants used in the
      treatment of malaria.
AB  - AIM OF THE STUDY: In our study, methanol, dichloromethane and aqueous extracts of
      13 Rwandan medicinal plants used in the treatment of malaria were tested for in
      vitro antiplasmodial activity. MATERIALS AND METHODS: The growth inhibition of
      chloroquine-sensitive Plasmodium falciparum strain (3D7) was evaluated using the
      measurement of lactate dehydrogenase activity. The active extracts were also
      tested against the chloroquine-resistant Plasmodium falciparum strain (W2) and
      for cytotoxicity assay using human normal foetal lung fibroblasts (WI-38).
      RESULTS: The majority of the plants tested showed an antiplasmodial activity and
      the best results were observed with dichloromethane leaf and flower extracts of
      Tithonia diversifolia, leaf extract of Microglossa pyrifolia and root extract of
      Rumex abyssinicus, methanol leaf extract of Fuerstia africana, root bark extracts
      of Zanthoxylum chalybeum and methanol bark extract of Terminalia mollis. Those
      extracts were active (IC(50)<15mug/ml) on both chloroquine-sensitive and
      resistant strains of Plasmodium falciparum. Zanthoxylum chalybeum, Solanecio
      mannii and Terminalia mollis presented the best selectivity index. CONCLUSIONS:
      The traditional use of most of the plant evaluated was confirmed by the
      antiplasmodial test. This study revealed for the first time the antiplasmodial
      activity of two plants: Terminalia mollis and Rumex abyssinicus.

PMID- 20035854
TI  - Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced
      liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9
      and TIMP-1.
AB  - AIM OF THE STUDY: To investigate the effect of Fraxinus rhynchophylla ethanol
      extract (FR(EtOH)) on liver fibrosis induced by carbon tetrachloride (CCl(4)) in
      rats. MATERIALS AND METHODS: Rat hepatic fibrosis was induced by oral
      administration of CCl(4). Sixty SD rats were divided randomly into 6 groups:
      control, CCl(4) group, silymarin group and three FR(EtOH)-treated groups. Except
      for the rats in control group, all rats were administered orally with CCl(4)
      (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FR(EtOH) groups
      were treated daily with FR(EtOH) (0.1, 0.5 and 1.0 g/kg, p.o.) throughout the
      whole experimental period. Liver function parameters (such as activities of serum
      GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase,
      SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the
      liver fibrosis pathway were detected. RESULTS: The results showed that FR(EtOH)
      (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT
      and sGPT caused by CCl(4). FR(EtOH) (0.1 and 0.5 g/kg BW) and significantly
      increased the activities of GSH-Px. The histopathological study showed that
      FR(EtOH) (0.1 and 0.5 g/kg BW) reduced the incidence of liver lesions, including
      hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization
      hepatic necrosis and fibrous connective tissue proliferated induced by CCl(4) in
      rats. In our study it was showed that CCl(4)-treated group significantly
      increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR(EtOH) (0.1 and
      0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1.
      Finally, the amount of esculetin in the FR(EtOH) was 33.54 mg/g extract.
      CONCLUSIONS: Oral administration of FR(EtOH) significantly reduces CCl(4)-induced
      hepatic fibrosis in rats, probably by exerting a protective effect against
      hepatocellular fibrosis by its free radical scavenging ability. FR(EtOH) down
      regulated the expressions of uPA, MMP-2 and MMP-9 in CCl(4)-induced liver
      fibrosis in rats.

PMID- 20035855
TI  - Effect of plants used in Mexico to treat gastrointestinal disorders on charcoal
      gum acacia-induced hyperperistalsis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: A total of 28 plant extracts, belonging to 26
      different plant species are commonly used in Traditional Mexican Medicine for the
      treatment of gastrointestinal disorders such as diarrhea. AIM OF THE STUDY: To
      evaluate the effect of medicinal plant extracts on induced hyperperistalsis in
      rats. MATERIALS AND METHODS: Charcoal meal test was used in this study. Extracts
      were tested at a dose of 300mg/kg. RESULTS: From all the plant extracts tested,
      only Geranium mexicanum (roots) showed 100% of inhibition. The extracts of
      Artemisia absinthium, Matricaria recutita, Caesalpinia pulcherrima, Lygodium
      venustum, Chenopodium ambrosoides (green variety), Aloysia triphylla, Artemisia
      ludoviciana, Chiranthodendron pentadactylon, and Cocos nucifera showed moderate
      inhibitory activity with values ranging from 30 to 57%. Their activities were
      greater than that of or equal to loperamide (34% of inhibition at doses of
      10mg/kg) drug used as control. The remaining plants exhibited marginal or null
      inhibitory effect on hyperpropulsive movement of the small intestine.
      CONCLUSIONS: The results obtained in this study give some scientific support to
      the popular use of 23 of the plants tested for the treatment of gastrointestinal
      disorders such as diarrhea in Mexican traditional medicine. However, roots of
      Geranium mexicanum should be used in herbal medicine with care to avoid toxicity.

PMID- 20035857
TI  - Paraquat increases connective tissue growth factor and collagen expression via
      angiotensin signaling pathway in human lung fibroblasts.
AB  - Survivors of paraquat poisoning are left with pulmonary fibrosis which results in
      a restrictive type of long-term pulmonary dysfunction. Connective tissue growth
      factor (CTGF) is a key growth factor that initiates tissue repair and underlies
      the development of lung fibrosis. Angiotensin (ANG) II may induce CTGF expression
      in the heart and kidney and plays an important role in the pathogenesis of lung
      fibrosis. The biological effects of ANG II are mediated by ANG II type 1 receptor
      (AT1R) and AT2R. The aims of this study were to investigate the effects of
      paraquat on ANG II, ANG II receptors, CTGF, and collagen expressions and to
      assess the role of ANG II receptors in paraquat-induced collagen synthesis in
      human lung fibroblasts (MRC-5). MRC-5 cells were incubated with various
      concentrations of paraquat with or without the ANG II receptor antagonist,
      saralasin. Paraquat increased ANG II production and AT1R mRNA and protein
      expression and decreased AT2R mRNA expression. Furthermore, paraquat treatment
      increased CTGF and collagen mRNA and protein expression in a dose-dependent
      manner and saralasin inhibited these effects. These results indicate that
      paraquat increases CTGF and collagen expression by activating angiotensin
      signaling pathway in human lung fibroblasts.

PMID- 20035856
TI  - Age-dependent decreases in DNA methyltransferase levels and low transmethylation
      micronutrient levels synergize to promote overexpression of genes implicated in
      autoimmunity and acute coronary syndromes.
AB  - T cell DNA methylation levels decline with age, activating genes such as KIR and
      TNFSF7 (CD70), implicated in lupus-like autoimmunity and acute coronary
      syndromes. The mechanisms causing age-dependent DNA demethylation are unclear.
      Maintenance of DNA methylation depends on DNA methyltransferase 1 (Dnmt1) and
      intracellular S-adenosylmethionine (SAM) levels, and is inhibited by S
      adenosylhomocysteine (SAH). SAM levels depend on dietary micronutrients including
      folate and methionine. SAH levels depend on serum homocysteine concentrations. T
      cell Dnmt1 levels also decline with age. We hypothesized that age-dependent Dnmt1
      decreases synergize with low folate, low methionine or high homocysteine levels
      to demethylate and activate methylation-sensitive genes. T cells from healthy
      adults ages 22-81, stimulated and cultured with low folate, low methionine, or
      high homocysteine concentrations showed demethylation and overexpression of KIR
      and CD70 beginning at age approximately 50 and increased further with age. The
      effects were reproduced by Dnmt1 knockdowns in T cells from young subjects. These
      results indicate that maintenance of T cell DNA methylation patterns is more
      sensitive to low folate and methionine levels in older than younger individuals,
      due to low Dnmt1 levels, and that homocysteine further increases aberrant gene
      expression. Thus, attention to proper nutrition may be particularly important in
      the elderly.

PMID- 20035858
TI  - Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo
      following peripheral nerve injury.
AB  - Spinal release of cytokines may play a critical role in the maladapted
      nociceptive signaling underlying chronic pain states. In order to investigate
      this biology, we have developed a novel 'high flux' intrathecal microdialysis
      approach in combination with multiplex bead-based immunoassay technology to
      concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and
      tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic
      constriction injury (CCI). Intrathecal microdialysis was performed under
      isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity.
      In a first study, C-fiber strength electrical stimulation of the operated nerve
      in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux (
      approximately 15-fold) that was significantly greater than that observed in the
      sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent
      stimulation, whereas TNFalpha was not. In a second study, treatment with the
      glial inhibitor propentofylline for 7days normalized CCI-induced mechanical
      hypersensitivity. In the same animals, this treatment also significantly reduced
      intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked
      cytokine release of both IL-1beta and IL-6. These results provide support for
      glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha
      that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our
      studies demonstrate the ability of a neurone-glia signaling mechanism to
      dynamically modulate this release and support a role of spinal IL-1beta in the
      phasic transmission of abnormal pain signals.

PMID- 20035859
TI  - Methamphetamine sensitization attenuates the febrile and neuroinflammatory
      response to a subsequent peripheral immune stimulus.
AB  - Methamphetamine (MA) use is associated with activation of microglia and, at high
      doses, can induce neurotoxicity. Given the changes in the neuroinflammatory
      environment associated with MA, we investigated whether MA sensitization, a model
      of stimulant psychosis and an indicator of drug addiction, would interfere with
      the thermoregulatory and neuroinflammatory response to a subsequent peripheral
      immune stimulus. C57BL6/J mice were given either 1 mg/kg MA or saline i.p. once a
      day for 5 days to produce behavioral sensitization. Seventy-two hours following
      the last MA injection, 100 microg/kg LPS or saline was co-administered with 1
      mg/kg MA or saline and blood and brains were collected. Here we report that while
      co-administration of LPS and MA did not affect the LPS-induced increase in
      central cytokine mRNA, mice sensitized to MA showed an attenuated central
      response to LPS. Interestingly, the peripheral response to LPS was not affected
      by MA sensitization. Plasma cytokines increased similarly in all groups after
      LPS. Further, c-Fos expression in the nucleus of the solitary tract did not
      differ between groups, suggesting that the periphery-to-brain immune signal is
      intact in MA-sensitized mice and that the deficit lies in the central cytokine
      compartment. We also show that MA sensitization decreased LPS- or acute MA
      induced microglial Iba1 expression compared to non-sensitized mice. Taken
      together, these data show that MA sensitization interferes with the normal
      central immune response, preventing the CNS from efficiently responding to
      signals from the peripheral immune system.

PMID- 20035860
TI  - Food aversion: a critical balance between allergen-specific IgE levels and taste
      preference.
AB  - Animals sensitized to allergens change their feeding behavior and avoid drinking
      the otherwise preferred sweetened solutions containing the allergens. This
      phenomenon, known as food aversion, appears to be mediated by allergen-specific
      IgE antibodies. Here we investigated food aversion in BALB/c and C57BL/6 mice,
      which differ in their allergic responses to the allergen ovalbumin as well as in
      their preference for sweet taste. BALB/c mice present higher levels of IgE and a
      natural lower preference for sweet flavors when compared to C57BL/6 mice.
      Specifically, we studied a conflicting situation in which animals simultaneously
      experienced the aversive contact with the allergen and the attractive sweet taste
      of increasing concentrations of sucrose. We found that BALB/c mice were more
      prone to develop food aversion than C57BL/6 mice and that this aversive behavior
      could be abolished in both strains by increasing the palatability of the solution
      containing the allergen. In both strains food aversion was positively correlated
      with the levels of allergen-specific IgE antibodies and inversely correlated with
      their preference for sucrose sweetened solutions.

PMID- 20035861
TI  - Tempol ameliorates murine viral encephalomyelitis by preserving the blood-brain
      barrier, reducing viral load, and lessening inflammation.
AB  - Multiple sclerosis (MS) is a progressive inflammatory and/or demyelinating
      disease of the human central nervous system (CNS). Most of the knowledge about
      the pathogenesis of MS has been derived from murine models, such as experimental
      autoimmune encephalomyelitis and viral encephalomyelitis. Here, we infected
      female C57BL/6 mice with a neurotropic strain of the mouse hepatitis virus (MHV
      59A) to evaluate whether treatment with the multifunctional antioxidant tempol (4
      hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) affects the ensuing
      encephalomyelitis. In untreated animals, neurological symptoms developed quickly:
      90% of infected mice died 10 days after virus inoculation and the few survivors
      presented neurological deficits. Treatment with tempol (24 mg/kg, ip, two doses
      on the first day and daily doses for 7 days plus 2 mM tempol in the drinking
      water ad libitum) profoundly altered the disease outcome: neurological symptoms
      were attenuated, mouse survival increased up to 70%, and half of the survivors
      behaved as normal mice. Not surprisingly, tempol substantially preserved the
      integrity of the CNS, including the blood-brain barrier. Furthermore, treatment
      with tempol decreased CNS viral titers, macrophage and T lymphocyte infiltration,
      and levels of markers of inflammation, such as expression of inducible nitric
      oxide synthase, transcription of tumor necrosis factor-alpha and interferon
      gamma, and protein nitration. The results indicate that tempol ameliorates murine
      viral encephalomyelitis by altering the redox status of the infectious
      environment that contributes to an attenuated CNS inflammatory response. Overall,
      our study supports the development of therapeutic strategies based on nitroxides
      to manage neuroinflammatory diseases, including MS.

PMID- 20035863
TI  - Monocarboxylate transport in human corneal epithelium and cell lines.
AB  - Monocarboxylate transporters (MCTs) are transmembrane proteins capable of
      transferring lactate and other endogenous and exogenous monocarboxylates across
      the cell membrane. The aim of the present study was to assess the expression and
      transporter role of human MCT1, MCT3 and MCT4 in the corneal epithelium, corneal
      epithelial cell lines (primary HCEpiC and immortalized HCE cells) and isolated
      rabbit corneas. MCT1 and MCT4 were expressed in the human corneal epithelium and
      the cell lines at mRNA and protein levels. Cellular uptake studies showed
      saturable and pH-dependent l-lactic acid transport, which was inhibited by
      various monocarboxylates like diclofenac and flurbiprofen. The permeability of
      benzoic acid across the rabbit cornea was higher in absorptive direction and this
      directionality was diminished in the presence of monocarboxylate drug valproic
      acid. Monocarboxylate transport was functional in the human corneal epithelial
      cells and rabbit cornea and it may play a role in the ocular drug absorption.

PMID- 20035864
TI  - The pharmacokinetics of orally administered S-carboxymethyl-L-cysteine in the
      dog, calf and sheep.
AB  - The aim of this study was to investigate the feasibility of employing S
      carboxymethyl-L-cysteine as a treatment of chronic obstructive pulmonary disease
      in dogs. To this end the pharmacokinetic parameters of orally administered S
      carboxymethyl-L-cysteine were determined in the dog, cow and sheep. Six healthy
      beagle dogs, six endogenous Greek sheep and four Holstein Fresian calves were
      orally dosed with 10 mg/kg body weight of S-carboxymethyl-L-cysteine. No
      significant differences in T(max) and T(1/2) were reported between the species.
      However, significantly higher AUC((0-last)), 21.56+/-6.67 microg h ml(-1) and
      AUC((0-infinity)), 21.63+/-6.68 microg h ml(-1) were seen in the dogs compared to
      the sheep and calves. The calculated V(D) was significantly higher in the sheep
      (10.4+/-2.7 L kg(-1)) and the calves (3.8+/-0.7 L kg(-1)) compared to the dogs
      (1.0+/-0.6 L kg(-1)). The rank order of increasing C(L) was sheep (3.4+/-2.7 L h(
      1)kg(-1))>calves (2.7+/-0.4 L h(-1) kg(-1))>dogs (0.5+/-0.2 L h(-1)kg(-1)). The
      result for the dogs was significantly lower that the calculated C(L) for the
      sheep and calves. All these results indicate that the oral administration of S
      carboxymethyl-L-cysteine may be useful during the therapeutic management of
      chronic obstructive pulmonary disease in dogs.

PMID- 20035865
TI  - Preparation and in vitro-in vivo evaluation of Witepsol H35 based self
      nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).
AB  - Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery
      systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature
      of the drug. Screening of oil phase, surfactants and co-surfactants were
      performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively.
      Ternary phase diagrams were drawn to identify nanoemulsifying region followed by
      optimization of SNEDDS formulation. The optimized formulation, CoQ(10), Witepsol
      H35, Solutol HS15 and Lauroglycol FCC in the weight ratio of 1:0.7:4:2,
      respectively, emulsified readily at 37 degrees C with mean emulsion droplet size
      of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8
      buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution
      (emulsification) test and in vivo animal study of the formulation elucidated the
      complete emulsification of drug and improved oral bioavailability of poorly
      soluble CoQ(10).

PMID- 20035862
TI  - Genetics of hypertension: from experimental animals to humans.
AB  - Essential hypertension affects 20 to 30% of the population worldwide and
      contributes significantly to cardiovascular mortality and morbidity. Heridability
      of blood pressure is around 15 to 40% but there are also substantial
      environmental factors affecting blood pressure variability. It is assumed that
      blood pressure is under the control of a large number of genes each of which has
      only relatively mild effects. It has therefore been difficult to discover the
      genes that contribute to blood pressure variation using traditional approaches
      including candidate gene studies and linkage studies. Animal models of
      hypertension, particularly in the rat, have led to the discovery of quantitative
      trait loci harbouring one or several hypertension related genes, but translation
      of these findings into human essential hypertension remains challenging. Recent
      development of genotyping technology made large scale genome-wide association
      studies possible. This approach and the study of monogenic forms of hypertension
      has led to the discovery of novel and robust candidate genes for human essential
      hypertension, many of which require functional analysis in experimental models.

PMID- 20035867
TI  - The trehalose transporter 1 gene sequence is conserved in insects and encodes
      proteins with different kinetic properties involved in trehalose import into
      peripheral tissues.
AB  - We recently cloned a trehalose transporter gene (Tret1) that contributes to
      anhydrobiosis induction in the sleeping chironomid Polypedilum vanderplanki
      Hinton. Because trehalose is the main haemolymph sugar in most insects, they
      might possess Tret1 orthologs involved in maintaining haemolymph trehalose
      levels. We cloned Tret1 orthologs from four species in three insect orders. The
      similarities of the amino acid sequence to TRET1 in P. vanderplanki were 58.5
      80.4%. Phylogenetic analysis suggested the Tret1 sequences were conserved in
      insects. The Xenopus oocyte expression system showed apparent differences in the
      K(m) and V(max) values for trehalose transport activity among the six proteins
      encoded by the corresponding orthologs. The TRET1 orthologs of Anopheles gambiae
      (K(m): 45.74 +/- 3.58 mM) and Bombyx mori (71.58 +/- 6.45 mM) showed low
      trehalose affinity, whereas those of Apis mellifera (9.42 +/- 2.37 mM) and
      Drosophila melanogaster (10.94 +/- 7.70 mM) showed high affinity. This difference
      in kinetics might be reflected in the haemolymph trehalose:glucose ratio of each
      species. Tret1 was expressed not only in the fat body but also in muscle and
      testis. These findings suggest that insect TRET1 is responsible for the release
      of trehalose from the fat body and the incorporation of trehalose into other
      tissues that require a carbon source, thereby regulating trehalose levels in the
      haemolymph.

PMID- 20035868
TI  - Detection of donor-specific HLA antibodies before and after removal of a rejected
      kidney transplant.
AB  - Serum analysis of patients considered for retransplantation has a potential
      limitation that the rejected allograft may absorb HLA antibodies. We have
      determined how the highly sensitive micro bead-based Luminex antibody-binding
      assay with single antigens can detect donor-specific HLA antibodies (DSA) in
      patients before and after surgical removal of a rejected allograft. This analysis
      was done for 65 allograft nephrectomy (allonx) cases contributed by 16
      laboratories worldwide. In the HLA-A,B and -DRB1 mismatch categories the
      incidence of DSA reactivity pre-allonx and post-allonx was 64% vs 87% (p=0.0033)
      and 57% vs 86% (p=0.001), respectively. The frequencies of individual reactive
      antigens were also lower before allonx: for HLA-A,B antigens: 49% vs 75%
      (p<0.0001) and DRB1 antigens: 48% vs 79% (p=0.0001). On the other hand, no
      significant differences were seen between the pre-allonx and post-allonx
      frequencies of DSA to DRB3/4/5 (65% vs 78%, p=0.22) and DQ mismatches (76% vs
      87%, p=0.18). CONCLUSION: although the sensitive Luminex antibody assay can
      detect anti-donor antibodies in the presence of a rejected transplant, it is
      apparent that the antibody specificity pattern is often incomplete especially
      against the HLA-A, -B and DR mismatches. This understanding seems relevant to the
      determination of acceptable mismatches for patients considered for
      retransplantation.

PMID- 20035870
TI  - Implantable brain computer interface: challenges to neurotechnology translation.
AB  - This article reviews three concepts related to implantable brain computer
      interface (BCI) devices being designed for human use: neural signal extraction
      primarily for motor commands, signal insertion to restore sensation, and
      technological challenges that remain. A significant body of literature has
      occurred over the past four decades regarding motor cortex signal extraction for
      upper extremity movement or computer interface. However, little is discussed
      regarding postural or ambulation command signaling. Auditory prosthesis research
      continues to represent the majority of literature on BCI signal insertion.
      Significant hurdles continue in the technological translation of BCI implants.
      These include developing a stable neural interface, significantly increasing
      signal processing capabilities, and methods of data transfer throughout the human
      body. The past few years, however, have provided extraordinary human examples of
      BCI implant potential. Despite technological hurdles, proof-of-concept animal and
      human studies provide significant encouragement that BCI implants may well find
      their way into mainstream medical practice in the foreseeable future.

PMID- 20035869
TI  - Expression of CXCR6 on CD8(+) T cells was up-regulated in allograft rejection.
AB  - CXCL16/SR-PSOX is a novel transmembrane-type chemokine, which was also identified
      as a novel scavenger receptor for oxidized low density lipoprotein. Its receptor
      CXCR6 expresses on activated CD8(+) T cells, type 1-polarized CD4(+), and
      constitutively expresses on NKT cells. Moreover, it has been shown that CXCL16
      accumulated activated CD8(+) T cells to sites of inflammation. To date, the
      effect of CXCL16 (SR-PSOX)/CXCR6 on CD8(+) T cells and its role in allograft
      rejection/acceptance are not well understood. In the current study, we show that
      rejected allografts showed higher expressions of CXCR6 and CXCL16. More
      importantly, expression of CXCR6 on CD8(+) T cells was also up-regulated by
      rejection. However, the blockade of CXCL16(SR-PSOX)/CXCR6 interaction could not
      inhibit cytotoxic activity of CD8(+) T cells, and therefore, could not prolong
      the cardiac graft survival time.

PMID- 20035866
TI  - Central effects of estradiol in the regulation of food intake, body weight, and
      adiposity.
AB  - In recent years, obesity and its associated health disorders and costs have
      increased. Accumulation of adipose tissue, or fat, in the intra-abdominal adipose
      depot is associated with an increased risk of developing cardiovascular problems,
      type-2 diabetes mellitus, certain cancers, and other disorders like the metabolic
      syndrome. Males and females differ in terms of how and where their body fat is
      stored, in their hormonal secretions, and in their neural responses to signals
      regulating weight and body fat distribution. Men and post-menopausal women
      accumulate more fat in their intra-abdominal depots than pre-menopausal women,
      resulting in a greater risk of developing complications associated with obesity.
      The goal of this review is to discuss the current literature on sexual
      dimorphisms in body weight regulation, adipose tissue accrual and deposition.

PMID- 20035871
TI  - Local translation of dendritic RhoA revealed by an improved synaptoneurosome
      preparation.
AB  - Changes in dendritic spine morphology, a hallmark of synaptic plasticity, involve
      remodeling of the actin cytoskeleton, a process that is regulated by Rho GTPases.
      RhoA, a member of this GTPase family, segregates to dendrites in differentiated
      neurons. Given the emerging role of dendritic mRNA local translation in synaptic
      plasticity, we have assessed the possible localization and translation of RhoA
      mRNA at dendrites. At this end, we have developed and describe here in detail an
      improved method for isolating hippocampal and neocortical mouse
      synaptoneurosomes. This synaptoneurosomal preparation is much more enriched in
      synaptic proteins than those obtained in former methods, exhibits bona fide
      electron microscopy pre- and postsynaptic morphologies, contains abundant
      dendritic mRNAs, and is competent for activity-regulated protein synthesis. Using
      this preparation, we have found that RhoA mRNA is dendritically localized and its
      local translation is enhanced by BDNF stimulation. These findings suggest that
      some of the known functions of RhoA on spine morphology may be mediated by
      regulating its local translation.

PMID- 20035872
TI  - Multiple-Particle-Tracking to investigate viscoelastic properties in living
      cells.
AB  - Cell mechanical properties play an important role in determining many cellular
      activities. Passive microrheology techniques, such as Multiple-Particle-Tracking
      (MPT) give an insight into the structural rearrangements and viscoelastic
      response of a wide range of materials, in particular soft materials and complex
      fluids like cell cytoplasm in living cells. The technique finds an important
      field of application in large cells such as oocytes where, during their growth,
      several organelles and molecules are displaced in specific territories of the
      cell instrumental for later embryonic development. To measure cell mechanics,
      cells are usually deformed by many techniques that are slow and often invasive.
      To overcome these limits, the MPT technique is applied. Probe particles are
      embedded in the viscoelastic sample and their properties are extracted from the
      thermal fluctuation spectra measured using digital video-microscopy. The Brownian
      motion of a probe particle immersed in a network is directly related to the
      network's mechanical properties. Particles exhibit larger motions when their
      local environments are less rigid or less viscous. The mean-square-displacement
      (MSD) of the particle's trajectory is used to quantify its amplitude of motions
      over different time scales.

PMID- 20035873
TI  - Raman spectroscopy of Xenopus laevis oocytes.
AB  - This work reports on the application of Raman spectroscopy for the analysis of
      Xenopus laevis oocytes (stage-I). A two-color home-made microscope has been used
      for this investigation. In particular, a 785nm Raman probe has been used to
      acquire the spontaneous Raman scattering from the oocyte cytoplasm, while a 532nm
      probe has been employed to detect carotenoids through Resonant Raman Scattering.
      Finally, the distribution of beta-carotene along a diameter of a single oocyte
      has been investigated.

PMID- 20035874
TI  - Engineered gene clusters for the production of the antimicrobial peptide microcin
      J25.
AB  - Microcin J25 (MccJ25) is an antimicrobial peptide produced by isolates of
      Escherichia coli with activity against closely related species. Production and
      export of mature MccJ25 in E. coli requires four genes that are organized on a
      plasmid-borne cluster in natural producer strains. In these strains, MccJ25
      production does not commence until the cells reach stationary phase, and,
      according to previous literature, the highest titers of MccJ25 are obtained from
      cells grown in nutrient-poor medium. We sought to design an engineered MccJ25
      gene cluster that alleviated the growth phase and media limitations of the
      natural cluster. In contrast to previous reports, we observe here that production
      of MccJ25 from its natural cluster is efficient in rich media, such as Luria
      Bertani (LB). The engineered gene cluster functions in several E. coli strains
      and produces titers of MccJ25 that are moderately increased (1.5- to 2-fold)
      relative to the natural cluster. RT-PCR experiments and translational GFP fusion
      experiments confirm that the engineered cluster produces MccJ25 throughout
      exponential phase. Furthermore, we provide evidence that control of the natural
      MccJ25 gene cluster is at the transcriptional level. The observations herein
      provide design parameters for large-scale production of MccJ25 for
      biotechnological applications.

PMID- 20035875
TI  - Complementary effects of multi-protein components on biomineralization in vitro.
AB  - The extracellular matrix (ECM) is composed of mixed protein fibers whose precise
      composition affects biomineralization. New methods are needed to probe the
      interactions of these proteins with calcium phosphate mineral and with each
      other. Here we follow calcium phosphate mineralization on protein fibers self
      assembled in vitro from solutions of fibronectin, elastin and their mixture. We
      probe the surface morphology and mechanical properties of the protein fibers
      during the early stages. The development of mineral crystals on the protein
      matrices is also investigated. In physiological mineralization solution, the
      elastic modulus of the fibers in the fibronectin-elastin mixture increases to a
      greater extent than that of the fibers from either pure protein. In the presence
      of fibronectin, longer exposure in the mineral solution leads to the formation of
      amorphous calcium phosphate particles templated along the self-assembled fibers,
      while elastin fibers only collect calcium without any mineral observed during
      early stage. TEM images confirm that small needle-shape crystals are confined
      inside elastin fibers which suppress the release of mineral outside the fibers
      during late stage, while hydroxyapatite crystals form when fibronectin is
      present. These results demonstrate complementary actions of the two ECM proteins
      fibronectin and elastin to collect cations and template mineral, respectively.

PMID- 20035876
TI  - Structural and functional analyses of Mycobacterium tuberculosis Rv3315c-encoded
      metal-dependent homotetrameric cytidine deaminase.
AB  - The emergence of drug-resistant strains of Mycobacterium tuberculosis, the
      causative agent of tuberculosis, has exacerbated the treatment and control of
      this disease. Cytidine deaminase (CDA) is a pyrimidine salvage pathway enzyme
      that recycles cytidine and 2'-deoxycytidine for uridine and 2'-deoxyuridine
      synthesis, respectively. A probable M. tuberculosis CDA-coding sequence (cdd,
      Rv3315c) was cloned, sequenced, expressed in Escherichia coli BL21(DE3), and
      purified to homogeneity. Mass spectrometry, N-terminal amino acid sequencing, gel
      filtration chromatography, and metal analysis of M. tuberculosis CDA (MtCDA) were
      carried out. These results and multiple sequence alignment demonstrate that MtCDA
      is a homotetrameric Zn(2+)-dependent metalloenzyme. Steady-state kinetic
      measurements yielded the following parameters: K(m)=1004 microM and k(cat)=4.8s(
      1) for cytidine, and K(m)=1059 microM and k(cat)=3.5s(-1) for 2'-deoxycytidine.
      The pH dependence of k(cat) and k(cat)/K(M) for cytidine indicate that
      protonation of a single ionizable group with apparent pK(a) value of 4.3
      abolishes activity, and protonation of a group with pK(a) value of 4.7 reduces
      binding. MtCDA was crystallized and crystal diffracted at 2.0 A resolution.
      Analysis of the crystallographic structure indicated the presence of a Zn(2+)
      coordinated by three conserved cysteines and the structure exhibits the canonical
      cytidine deaminase fold.

PMID- 20035877
TI  - 3D segmentation of cell boundaries from whole cell cryogenic electron tomography
      volumes.
AB  - Cryogenic electron tomography (cryo-ET) has gained increasing interest in recent
      years due to its ability to image whole cells and subcellular structures in 3D at
      nanometer resolution in their native environment. However, due to dose
      restrictions and the inability to acquire high tilt angle images, the
      reconstructed volumes are noisy and have missing information. Thus, features are
      unreliable, and precision extraction of the cell boundary is difficult, manual
      and time intensive. This paper presents an efficient recursive algorithm called
      BLASTED (Boundary Localization using Adaptive Shape and Texture Discovery) to
      automatically extract the cell boundary using a conditional random field (CRF)
      framework in which boundary points and shape are jointly inferred. The algorithm
      learns the texture of the boundary region progressively, and uses a global shape
      model and shape-dependent features to propose candidate boundary points on a
      slice of the membrane. It then updates the shape of that slice by accepting the
      appropriate candidate points using local spatial clustering, the global shape
      model, and trained boosted texture classifiers. The BLASTED algorithm segmented
      the cell membrane over an average of 93% of the length of the cell in 19
      difficult cryo-ET datasets.

PMID- 20035878
TI  - Graphene oxide: a substrate for optimizing preparations of frozen-hydrated
      samples.
AB  - Graphene oxide is a hydrophilic derivative of graphene to which biological
      macromolecules readily attach, with properties superior to those of amorphous
      carbon films commonly used in electron microscopy. The single-layered crystalline
      lattice of carbon is highly electron transparent, and exhibits conductivity
      higher than amorphous carbon. Hence, graphene oxide is a particularly promising
      substrate for the examination of biological materials by electron microscopy. In
      this manuscript we compare graphene oxide films to commonly used amorphous carbon
      films, describing the use of graphene in optimizing the preparation of unstained,
      vitrified biological macromolecules.

PMID- 20035879
TI  - Genetics of primary cerebral gyrification: Heritability of length, depth and area
      of primary sulci in an extended pedigree of Papio baboons.
AB  - Genetic control over morphological variability of primary sulci and gyri is of
      great interest in the evolutionary, developmental and clinical neurosciences.
      Primary structures emerge early in development and their morphology is thought to
      be related to neuronal differentiation, development of functional connections and
      cortical lateralization. We measured the proportional contributions of genetics
      and environment to regional variability, testing two theories regarding regional
      modulation of genetic influences by ontogenic and phenotypic factors. Our
      measures were surface area, and average length and depth of eleven primary
      cortical sulci from high-resolution MR images in 180 pedigreed baboons. Average
      heritability values for sulcal area, depth and length (h(2)(Area)=.38+/-.22;
      h(2)(Depth)=.42+/-.23; h(2)(Length)=.34+/-.22) indicated that regional cortical
      anatomy is under genetic control. The regional pattern of genetic contributions
      was complex and, contrary to previously proposed theories, did not depend upon
      sulcal depth, or upon the sequence in which structures appear during development.
      Our results imply that heritability of sulcal phenotypes may be regionally
      modulated by arcuate U-fiber systems. However, further research is necessary to
      unravel the complexity of genetic contributions to cortical morphology.

PMID- 20035880
TI  - Anatomical and functional parcellation of the human lateral premotor cortex.
AB  - The lateral premotor cortex (PM) of the macaque monkey is an anatomically
      multifaceted area, which serves multiple sensorimotor and cognitive functions.
      While evidence for the functional organization of human premotor cortex
      accumulates, much less is known about the underlying anatomical properties of
      this brain region. We used diffusion tractography and functional magnetic
      resonance imaging (fMRI) to investigate whether the precentral gyrus in humans
      can be segregated on the basis of anatomical connectivity and of functional
      activation in a set of cognitive and motor tasks. Tractographic data suggested a
      distinction between ventral and dorsal premotor cortex, and furthermore inferior
      and superior subparcellation of both. Functional MRI data corroborated these four
      areas, showing that anatomical parcellation predicts the distribution of
      functional activation and vice versa (preliminary evidence). These results may
      encourage the application of combining diffusion tractography and fMRI in vivo in
      order to shed light on the correspondence of brain function and anatomy.

PMID- 20035881
TI  - Regional grey matter volume abnormalities in bulimia nervosa and binge-eating
      disorder.
AB  - This study investigated whether bulimia nervosa (BN) and binge-eating disorder
      (BED) are associated with structural brain abnormalities. Both disorders share
      the main symptom binge-eating, but are considered differential diagnoses. We
      attempted to identify alterations in grey matter volume (GMV) that are present in
      both psychopathologies as well as disorder-specific GMV characteristics. Such
      information can help to improve neurobiological models of eating disorders and
      their classification. A total of 50 participants (patients suffering from BN
      (purge type), BED, and normal-weight controls) underwent structural MRI scanning.
      GMV for specific brain regions involved in food/reinforcement processing was
      analyzed by means of voxel-based morphometry. Both patient groups were
      characterized by greater volumes of the medial orbitofrontal cortex (OFC)
      compared to healthy controls. In BN patients, who had increased ventral striatum
      volumes, body mass index and purging severity were correlated with striatal grey
      matter volume. Altogether, our data implicate a crucial role of the medial OFC in
      the studied eating disorders. The structural abnormality might be associated with
      dysfunctions in food reward processing and/or self-regulation. The bulimia
      specific volume enlargement of the ventral striatum is discussed in the framework
      of negative reinforcement through purging and associated weight regulation.

PMID- 20035882
TI  - The influence of directed covert attention on emotional face processing.
AB  - Activation of the amygdala and the fusiform face area (FFA) are consistent
      findings in imaging studies on emotional face processing. There is evidence that
      these activations occur even when emotional faces are unattended; however, it was
      also shown that amygdala and FFA activation were modulated by the attentional
      resources allocated to these stimuli. Attentional resources might thereby not
      only depend on task demands but also on varying degrees of covert attention
      processes induced by the task. To address this issue we examined the isolated
      effect of covert shifts of spatial attention on emotional face processing using
      functional magnetic resonance imaging during a modified spatial cueing paradigm.
      Directional spatial and neutral cues were presented superimposed on neutral,
      happy, sad and fearful faces. Subjects performed a target detection task, while
      fixation was controlled by simultaneous eye tracking. Reaction times showed a
      strong cue validity effect across all emotions (i.e., faster responses for
      directional cues). Comparing directed to nondirected attention revealed a
      significantly reduced signal in the FFA irrespective of the emotional expression.
      This effect was also seen in bilateral amygdala, but only in trials including
      fearful faces. Our findings suggest that covert shifts of attention toward a
      specific location result in reduced face processing independent from task
      demands. Furthermore, our data show a task-irrelevant amygdala response specific
      to fearful faces under a wide attentional focus. Attentional disengagement from
      the faces led to a suppression of this amygdala response and thus provides
      further evidence that amygdala activation depends on the focus of attention.

PMID- 20035883
TI  - Remote sites of structural atrophy predict later amyloid formation in a mouse
      model of Alzheimer's disease.
AB  - Magnetic resonance (MR) imaging can provide a longitudinal view of neurological
      disease through repeated imaging of patients at successive stages of impairment.
      Until recently, the difficulty of manual delineation has limited volumetric
      analyses of MR data sets to a few select regions and a small number of subjects.
      Increased throughput offered by faster imaging methods, automated segmentation,
      and deformation-based morphometry have recently been applied to overcome this
      limitation with mouse models of neurological conditions. We use automated
      analyses to produce an unbiased view of volumetric changes in a transgenic mouse
      model for Alzheimer's disease (AD) at two points in the progression of disease:
      immediately before and shortly after the onset of amyloid formation. In addition
      to the cortex and hippocampus, where atrophy has been well documented in AD
      patients, we identify volumetric losses in the pons and substantia nigra where
      neurodegeneration has not been carefully examined. We find that deficits in
      cortical volume precede amyloid formation in this mouse model, similar to
      presymptomatic atrophy seen in patients with familial AD. Unexpectedly,
      volumetric losses identified by MR outside of the forebrain predict locations of
      future amyloid formation, such as the inferior colliculus and spinal nuclei,
      which develop pathology at very late stages of disease. Our work provides proof
      of-principle that MR microscopy can expand our view of AD by offering a complete
      and unbiased examination of volumetric changes that guide us in revisiting the
      canonical neuropathology.

PMID- 20035884
TI  - Distinct representations of phonemes, syllables, and supra-syllabic sequences in
      the speech production network.
AB  - Functional neuroimaging studies have converged on a core network of brain regions
      that supports speech production, but the sublexical processing stages performed
      by the different parts of this network remain unclear. Using an fMRI adaptation
      paradigm and quantitative analysis of patterns of activation rather than contrast
      subtractions alone, we were able to identify a set of neural substrates
      predominantly engaged in phonemic, syllabic, and supra-syllabic levels of
      processing during speech. Phoneme-level processes were found in the left SMA,
      pallidum, posterior superior temporal gyrus, and superior lateral cerebellum.
      Syllable-level processes were found in the left ventral premotor cortex, and
      supra-syllabic processes related to phonological chunking were found in the right
      superior lateral cerebellum. Active regions that were not sensitive to sublexical
      manipulations included primary motor and auditory cortical areas, and medial
      cerebellum. These results offer a quantitative technique for localizing
      sublexical neural processes that are difficult to dissociate using non-invasive
      imaging techniques and provide the beginnings of a "brain map" for language
      output.

PMID- 20035885
TI  - The time course of activity in dorsolateral prefrontal cortex and anterior
      cingulate cortex during top-down attentional control.
AB  - A network of brain regions has been implicated in top-down attentional control,
      including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior
      cingulate cortex (dACC). The present experiment evaluated predictions of the
      cascade-of-control model (Banich, 2009), which predicts that during attentionally
      demanding tasks, LDLPFC imposes a top-down attentional set which precedes late
      stage selection performed by dACC. Furthermore, the cascade-of-control model
      argues that dACC must increase its activity to compensate when top-down control
      by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense
      array ERP data collected from the same 80 participants in separate sessions. fMRI
      results guided ERP source modeling to characterize the time course of activity in
      LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity
      distinguished congruent and incongruent conditions on the Stroop task.
      Furthermore, when LDLPFC activity was low, the level of dACC activity was related
      to performance outcome. These results demonstrate that dACC responds to
      attentional demand in a flexible manner that is dependent on the level of LDLPFC
      activity earlier in a trial. Overall, results were consistent with the temporal
      course of regional brain function proposed by the cascade-of-control model.

PMID- 20035886
TI  - Probing the mysterious underpinnings of multi-voxel fMRI analyses.
AB  - Various arguments have been proposed for or against sub-voxel sensitivity or
      hyperacuity in functional magnetic resonance imaging (fMRI) at standard
      resolution. Sub-voxel sensitivity might exist, but nevertheless the performance
      of multi-voxel fMRI analyses is very likely to be dominated by a larger-scale
      organization, even if this organization is very weak. Up to now, most arguments
      are indirect in nature: they do not in themselves proof or contradict sub-voxel
      sensitivity, but they are suggestive, seem consistent or not with sub-voxel
      sensitivity, or show that the principle might or might not work. Here the
      previously proposed smoothing argument against hyperacuity is extended with
      simulations that include more realistic signal, noise, and analysis properties
      than any of the simulations presented before. These simulations confirm the
      relevance of the smoothing approach to find out the scale of the functional maps
      that underlie the outcome of multi-voxel analyses, at least in relative terms
      (differences in the scale of different maps). However, image smoothing, like most
      other arguments in the literature, is an indirect argument, and at the end of the
      day such arguments are not sufficient to decide the issue on whether and how much
      sub-voxel maps contribute. A few suggestions are made about the type of evidence
      that is needed to help us understand the as yet mysterious underpinnings of multi
      voxel fMRI analyses.

PMID- 20035887
TI  - Whole-brain anatomical networks: does the choice of nodes matter?
AB  - Whole-brain anatomical connectivity in living humans can be modeled as a network
      with diffusion-MRI and tractography. Network nodes are associated with distinct
      grey-matter regions, while white-matter fiber bundles serve as interconnecting
      network links. However, the lack of a gold standard for regional parcellation in
      brain MRI makes the definition of nodes arbitrary, meaning that network nodes are
      defined using templates employing either random or anatomical parcellation
      criteria. Consequently, the number of nodes included in networks studied by
      different authors has varied considerably, from less than 100 up to more than
      10(4). Here, we systematically and quantitatively assess the behavior, structure
      and topological attributes of whole-brain anatomical networks over a wide range
      of nodal scales, a variety of grey-matter parcellations as well as different
      diffusion-MRI acquisition protocols. We show that simple binary decisions about
      network organization, such as whether small-worldness or scale-freeness is
      evident, are unaffected by spatial scale, and that the estimates of various
      organizational parameters (e.g. small-worldness, clustering, path length, and
      efficiency) are consistent across different parcellation scales at the same
      resolution (i.e. the same number of nodes). However, these parameters vary
      considerably as a function of spatial scale; for example small-worldness
      exhibited a difference of 95% between the widely-used automated anatomical
      labeling (AAL) template (approximately 100 nodes) and a 4000-node random
      parcellation (sigma(AAL)=1.9 vs. sigma(4000)=53.6+/-2.2). These findings indicate
      that any comparison of network parameters across studies must be made with
      reference to the spatial scale of the nodal parcellation.

PMID- 20035888
TI  - The influence of restricted orientation rearing on map structure in primary
      visual cortex.
AB  - Visual experience is critical to the development of the structure of the primary
      visual cortex and, in turn, normal functional vision. The primary visual cortex
      contains maps of multiple features of the visual input, and these maps are
      characterised by specific types of geometric relationships. Manipulations of the
      visual environment during development in animals such as ferrets, cats and
      monkeys provide an opportunity to probe the rules governing map formation via
      their effect on these relationships. Here we use a computational model of map
      formation based on dimension-reduction principles to predict the effect on map
      relationships of presenting only a single orientation to one eye and the
      orthogonal orientation to the other eye. Since orientation preference and ocular
      dominance are now tightly coupled one might expect orientation and ocular
      dominance contours to lose their normally orthogonal relationship and instead run
      parallel to each other. However, surprisingly, the model predicts that orthogonal
      intersection can sometimes be preserved in this case. The model also predicts
      that orientation pinwheels can migrate from the centre to the borders of ocular
      dominance columns, and that the wavelengths of the ocular dominance and
      orientation maps can become coupled. These predictions provide a way to further
      test the adequacy of dimension reduction principles for explaining map structure
      under perturbed as well as normal rearing conditions, and thus allow us to deepen
      our understanding of the effect of the visual environment on visual cortical
      development.

PMID- 20035891
TI  - Comment on Braun and Huddleston "A molecular phylogenetic survey of
      caprimulgiform nightbirds illustrates the utility of non-coding sequences".

PMID- 20035889
TI  - Phylogenetic status of Xylaria subgenus Pseudoxylaria among taxa of the subfamily
      Xylarioideae (Xylariaceae) and phylogeny of the taxa involved in the subfamily.
AB  - To infer the phylogenetic relationships of Xylaria species associated with
      termite nests within the genus Xylaria and among genera of the subfamily
      Xylarioideae, beta-tubulin, RPB2, and alpha-actin sequences of 131 cultures of
      114 species from Xylaria and 11 other genera of the subfamily were analyzed.
      These 11 genera included Astrocystis, Amphirosellinia, Discoxylaria, Entoleuca,
      Euepixylon, Kretzschmaria, Nemania, Podosordaria, Poronia, Rosellinia, and
      Stilbohypoxylon. We showed that Xylaria species were distributed among three
      major clades, TE, HY, and PO, with clade TE-an equivalent of the subgenus
      Pseudoxylaria-encompassing exclusively those species associated with termite
      nests and the other two clades containing those associated with substrates other
      than termite nests. Xylaria appears to be a paraphyletic genus, with most of the
      11 genera submerged within it. Podosordaria and Poronia, which formed a distinct
      clade, apparently diverged from Xylaria and the other genera early. Species of
      Entoleuca, Euepixylon, Nemania, and Rosellinia constituted clade NR, a major
      clade sister to clade PO, while those of Kretzschmaria were inserted within clade
      HY and those of Astrocystis, Amphirosellinia, Discoxylaria, and Stilbohypoxylon
      were within clade PO.

PMID- 20035892
TI  - Troubleshooting tissue specificity and antibody selection: Procedures in
      immunohistochemical studies.
AB  - Optimal antigen detection and identification is dependent on the tissue of
      interest, the method of fixation, processing, and antibody specificity. We
      evaluated specific antigens in frozen middle cerebral artery (MCA) sections from
      rat brains under various conditions of fixation and differing primary and
      secondary antibody concentrations. Fresh MCAs were frozen, cryosectioned (8
      microm), and adhered to chrom-alum coated slides. The effects of different
      fixation and antigen retrieval/pretreatments were tested for detection of enzymes
      and receptors involved in MCA tone regulation. Antigen localization was
      determined with specific primary antibodies and detected using fluorochrome
      conjugated secondary antibodies. Spatial distribution of localized antigens was
      imaged using confocal microscopy. Frozen sections preserved the morphology of the
      endothelium and/or vessel wall within the tissue in a manner comparable to
      formalin-fixed sections. Fixation and tissue processing methods were modified
      based on the primary antibody used. Optimal antigen detection was obtained using
      fixatives such as 4% paraformaldehyde, 100% acetone or 100% methanol.
      Pretreatments, such as 1% SDS, enzymatic digestion using 0.1% trypsin, or
      application of heat were used to optimize antigen-antibody interaction. Stringent
      background and control checks were performed to ensure specificity of staining in
      both single and multiple labeling techniques. In a research setting where epitope
      detection is not used for diagnostic purposes, there is more latitude in tissue
      fixation. Frozen samples offer a more versatile method of linking the appropriate
      fixation and tissue processing to the primary antibody's unique needs. At the
      same time, it stabilizes the tissue in a format that allows for later analysis of
      multiple antigens with specific detection requirements in same tissue.

PMID- 20035893
TI  - De novo formation of basal bodies during cellular differentiation of Naegleria
      gruberi: progress and hypotheses.
AB  - Under defined laboratory conditions, Naegleria gruberi undergo an amoeba-to
      flagellate differentiation. During this differentiation, N. gruberi changes its
      shape from an amorphous amoeba to a regular shaped flagellate and forms de novo a
      flagellar apparatus, which is composed of two basal bodies, two flagella, a
      flagellar rootlet, and cytoplasmic microtubules. The entire process is
      accomplished within 2h after initiation of differentiation and more than 95% of
      cells in the population undergo this differentiation. This rapid and synchronous
      differentiation of N. gruberi provides us with a unique system in which we can
      study the process of de novo basal body assembly. In this review, I summarize
      recent findings associated with de novo basal body assembly and propose a
      hypothesis to explain how N. gruberi assemble two basal bodies per cell, which is
      what happens in the majority of cells.

PMID- 20035894
TI  - Role of microRNAs in ovarian cancer pathogenesis and potential clinical
      implications.
AB  - Despite important improvements over the past two decades, the overall cure rate
      of epithelial ovarian cancer (EOC) remains only approximately 30%. Although much
      has been learned about the proteins and pathways involved in early events of
      malignant transformation and drug resistance, a major challenge still remaining
      is the identification of markers for early diagnosis and prediction of response
      to chemotherapy. Recently, it has become clear that alterations in the expression
      of microRNAs (miRNAs) contribute to the pathogenesis and progression of several
      human malignancies. In this review we discuss current data concerning the
      accumulating evidence of the role of miRNAs in EOC pathogenesis and tumor
      characterization; their dysregulated expression in EOC; and their still undefined
      role in diagnosis, prognosis and prediction of response to therapy. The most
      frequently deregulated miRNAs are members of the let-7 and miR-200 families, the
      latter involved in epithelial-to-mesenchymal transition (EMT). EMT is part of
      normal ovarian surface epithelium physiology, being the key regulator of the post
      ovulatory repair process, and failure to undergo EMT may be one of the events
      leading to transformation. A general down-modulation of miRNA expression is
      observed in EOC compared to normal tissue. However, a clear consensus on the
      miRNA signatures associated with prognosis or prediction of response to therapy
      has not yet been reached.

PMID- 20035895
TI  - NFATc1: functions in osteoclasts.
AB  - NFATc1 is an important transcription factor which is critical for lineage
      selection in T-cell differentiation, cardiac valve morphogenesis, lymphatic
      endothelial development, osteoblast differentiation and osteoclastogenesis.
      Especially, it is a master regulator of RANKL-induced osteoclast differentiation
      and plays a pivotal role in osteoclast fusion and osteoclast activation via up
      regulation of various genes responsible for osteoclast adhesion, migration,
      acidification, degradation of inorganic and organic bone matrix. In the present
      review, some of the known features of NFATc1 such as structure, function and its
      roles in physiological or pathophysiological processes are highlighted.

PMID- 20035896
TI  - Recent advances in molecular imaging biomarkers in cancer: application of bench
      to bedside technologies.
AB  - Molecular imaging is the visualization, characterization and measurement of
      biological processes at the molecular and cellular level. In oncology, molecular
      imaging approaches can be directly applied as translational biomarkers of disease
      progression. In this article, selected imaging modalities are discussed with
      respect to this role. Recent studies focusing on emerging imaging biomarkers and
      new developments in the field are highlighted. Importantly, because ex vivo or
      tissue-based imaging now represents an important tool in the discovery and
      validation of oncology biomarkers, special attention is given to this resurgent
      field.

PMID- 20035897
TI  - Anomalous segmentation of Diphyllobothrium nihonkaiense.
AB  - An anomalous tapeworm with abnormal segmentation was obtained from a 6-year-old
      boy in Japan. The tapeworm consisted of proglottids with slanted anterior and
      posterior margins of proglottids and 4-6 sets of reproductive organs arranged
      between the margins. The morphology of the tapeworm did not correspond to any of
      the described cestodes. However, molecular identification based on nuclear and
      mitochondrial genes clearly showed the tapeworm was Diphyllobothrium
      nihonkaiense.

PMID- 20035898
TI  - Immune response of goats immunised with glutathione S-transferase and
      experimentally challenged with Fasciola hepatica.
AB  - Glutathione S-transferase (FhGST) purified from Fasciola hepatica adult worms was
      used to immunise goats against F. hepatica in an experimental infection; the
      level of protection, in terms of fluke burden, faecal egg counts and hepatic
      damage was determined, as well as the humoral and cellular immune response
      elicited. Animals were allocated into three groups of six animals each: group 1
      (immunised with FhGST and infected), group 2 (unimmunised and infected), and
      group 3 (unimmunised and uninfected). There was no significant reduction of fluke
      burden (9.3%) or faecal egg counts; hepatic damage was also similar in both
      infected groups. However, immunisation with FhGST induced the development of a
      well-defined immune response, characterized by the production of specific-FhGST
      antibodies as well as the appearance of circulating IL-4.

PMID- 20035899
TI  - Recruitment, enrollment and retention of young black men for HIV prevention
      research: experiences from The 411 for Safe Text project.
AB  - OBJECTIVE: There is abundant evidence of the HIV crisis in the black community,
      yet African Americans-and African American men in particular-are consistently
      under-represented in research on HIV prevention. The purpose of this paper is to
      describe the methods used to recruit and retain young black men in Philadelphia
      for an HIV prevention intervention. METHODS: We formed a partnership between
      community members, Media Education Entertainment (MEE) Productions, Inc., and
      academic researchers of the Colorado School of Public Health (CSPH). Recognizing
      the core principles of community-based participatory research (CBPR), face-to
      face recruitment was first conducted by MEE with the assistance of their
      community partners; subsequent enrollment and data collection were conducted over
      the telephone by staff in Colorado. RESULTS: We enrolled 58% of the young black
      men recruited, retained 77% of the young men for a follow-up survey at three
      months, and 65% of the initial enrollees were retained for the six-month follow
      up survey. Enrollment staff in Colorado reported initial challenges because of
      time elapse between recruitment and enrollment as well as participants'
      unfamiliarity with the enrollment staff. Subsequently, MEE recruitment staff
      emphasized the telephone area code and specific names of Colorado enrollment
      staff who would call. CONCLUSION: Our results demonstrate the importance of the
      community-academic partnership formed and adherence to the principles of CBPR in
      carrying out this work. Despite challenges in recruitment of racially and
      ethnically diverse participants for research, we successfully recruited,
      enrolled, and retained young black men in an HIV prevention program.

PMID- 20035900
TI  - Molecular evolution of Japanese encephalitis virus isolates from swine in Oita,
      Japan during 1980-2009.
AB  - In order to identify the patterns of genetic change of Japanese encephalitis
      virus (JEV) strains circulating in Oita, the complete envelope (E) gene has been
      sequenced for 35 isolates from swine in a 30-year span. Based on nucleotide and
      deduced amino acid sequences, the genetic variation was examined, phylogeny was
      estimated and selection pressures were also analyzed. This study demonstrated
      that the major genotype (G) of JEV isolates had shifted from GIII to GI in the
      mid-1990s in Oita. The intensities of selection acting on the Oita GIII and GI
      strains were found to be almost same. It suggests that the intensity of selection
      might not be the reason for such a genotype shift observed in Oita. Pairwise
      comparisons revealed the high conservation of the E gene at the protein level.
      Compared with the Oita GIII strains, all the Oita GI strains shared four amino
      acid changes at E129 (T-M), E222 (A-S), E327 (S-T) and E366 (A-S). Among all 70
      JEV isolates involved in this paper, the GI strains shared only one amino acid
      change at E222 (A-S) in comparison with the GIII strains. No strong evidence for
      positive selection was found, the JEV evolution has generally been subject to
      strong purifying selection, but one ongoing evolutionary pathway was found to be
      under relaxed purifying selection in Oita. This study is a localized example of
      JEV molecular evolution in nature.

PMID- 20035901
TI  - Development and validation of gene therapies in autoimmune diseases: Epidemiology
      to animal models.
AB  - Recent advancement in immunology, molecular biology, and bioinformatics has
      yielded extensive information on the pathophysiological mechanisms of
      autoimmunity, which has greatly facilitated the identification of potential
      therapeutic targets and the development of gene therapy in the treatment of
      autoimmune disease. Preclinical studies were carried out in animal models. This
      phenomenon is well illustrated in two prototypic animal models of autoimmune
      disease: the autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS)
      and collagen-induced arthritis (CIA) model in rheumatoid arthritis (RA). Here we
      discuss the current data on the development and validation of gene therapy in
      autoimmunity in these two models. The success in preclinical animal model studies
      provides the proof-of-concept of gene therapy for potential future applications
      in the treatment of autoimmune diseases. Furthermore, the identification of risk
      factors from epidemiological studies reveals further potential therapeutic
      targets to be examined in animal models.

PMID- 20035902
TI  - The epidemiology of transverse myelitis.
AB  - Transverse myelitis is a neurological disorder causing acute spinal cord injury
      as a result of acute inflammation, often associated with para infectious
      processes and autoimmune disease. The purpose of this article is to review the
      literature on the geoepidemiology of transverse myelitis and assess its
      environmental associations. Articles from 1981 to 2009 were reviewed in Pub Med
      along with potential causes such as autoimmune disease (focusing on systemic
      lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and
      Sjogren's), infection, vaccination, and intoxication.

PMID- 20035903
TI  - Early growth response transcription factors and the modulation of immune
      response: implications towards autoimmunity.
AB  - Early Growth Response (EGR) zinc finger transcription factors are induced under
      diverse mitogenic signals on different cell types such as lymphocytes. Their
      genetic expression does not require de novo protein synthesis, which suggests its
      role as immediate response mediators between cell surface receptor signaling and
      gene expression regulation. EGR factors are involved in modulating the immune
      response, by means of the induction of differentiation of lymphocyte precursors,
      activation of T and B cells, as well as their involvement in central and
      peripheral tolerance. The maturation state, particularly for B cells, and
      signaling through the T or B cell receptors seems to be quite relevant for the
      induction of the expression of these transcription factors. EGR-1 functions as a
      positive regulatory factor for B and T cells mediated by transcriptional
      regulation of key cytokines and costimulatory molecules, and its interaction with
      NFAT. On the opposite, EGR-2 and 3 act as negative regulators involved in anergy
      induction and apoptosis. EGR-2 and 3 deficiency has been related to the
      development of lupus like disease in murine models. The deficiency of these
      transcription factors has been associated to deficient Cbl-b expression, a
      resistant to anergy phenotype, and expansion of effector and activated T cells.

PMID- 20035904
TI  - Variability of the ventilatory response to Duffin's modified hyperoxic and
      hypoxic rebreathing procedure in healthy awake humans.
AB  - We quantified the magnitude of within- and between-day, within-subject
      variability of the ventilatory response to Duffin's modified rebreathing
      procedure in 20 healthy humans. The P(ETCO2) at which ventilation increased with
      progressive increases in P(ETCO2) during rebreathing was identified as the
      ventilatory recruitment threshold (VRT(CO2)); the ventilatory response below and
      above the VRT(CO2) was taken as an estimate of non-chemoreflex drives to breathe
      (V(EB)) and chemoreflex sensitivity (V(ES)), respectively. Within- and between
      day intraclass correlation coefficients for each of these parameters were >0.60
      (range: 0.62-0.93), indicating good-to-excellent test-retest reliability. Within-
      and between-day, within-subject coefficients of variation for hyperoxic and
      hypoxic V(EB) (range: 24.6-30.7%) and V(ES) (range: 18.5-32.7%) were relatively
      high but acceptable, while those for the VRT(CO2) were very small (range: 3.0
      3.8%). In conclusion, Duffin's modified rebreathing procedure, in both its
      hyperoxic and hypoxic form, is a highly reliable tool for measurement of
      chemoreflex and non-chemoreflex ventilatory control characteristics over short
      and long periods of time in healthy humans.

PMID- 20035905
TI  - Magnesium hydroxide temporarily enhancing osteoblast activity and decreasing the
      osteoclast number in peri-implant bone remodelling.
AB  - Repeated observations of enhanced bone growth around various degradable magnesium
      alloys in vivo raise the question: what is the major mutual origin of this
      biological stimulus? Several possible origins, e.g. the metal surface properties,
      electrochemical interactions and biological effects of alloying elements, can be
      excluded by investigating the sole bone response to the purified major corrosion
      product of all magnesium alloys, magnesium hydroxide (Mg(OH)(2)). Isostatically
      compressed cylinders of pure Mg(OH)(2) were implanted into rabbit femur condyles
      for 2-6 weeks. We observed a temporarily increased bone volume (BV/TV) in the
      vicinity of Mg(OH)(2) at 4 weeks that returned to a level that was equal to the
      control at 6 weeks. The osteoclast surface (OcS/BS) was significantly reduced
      during the first four weeks around the Mg(OH)(2) cylinder, while an increase in
      osteoid surface (OS/BS) was observed at the same time. At 6 weeks, the OcS/BS
      adjacent to the Mg(OH)(2) cylinder was back within the same range of the control.
      The mineral apposition rate (MAR) was extensively enhanced until 4 weeks in the
      Mg(OH)(2) group before matching the control. Thus, the enhanced bone formation
      and temporarily decreased bone resorption resulted in a higher bone mass around
      the slowly dissolving Mg(OH)(2) cylinder. These data support the hypothesis that
      the major corrosion product Mg(OH)(2) from any magnesium alloy is the major
      origin of the observed enhanced bone growth in vivo. Further studies have to
      evaluate if the enhanced bone growth is mainly due to the local magnesium ion
      concentration or the local alkalosis accompanying the Mg(OH)(2) dissolution.

PMID- 20035906
TI  - Porous biocompatible three-dimensional scaffolds of cellulose microfiber/gelatin
      composites for cell culture.
AB  - Physiological tissues, including brain and other organs, have three-dimensional
      (3-D) aspects that need to be supported to model them in vitro. Here we report
      the use of cellulose microfibers combined with cross-linked gelatin to make
      biocompatible porous microscaffolds for the sustained growth of brain cell and
      human mesenchymal stem cells (hMSCs) in 3-D structure. Live imaging using
      confocal microscopy indicated that 3-D microscaffolds composed of gelatin or
      cellulose fiber/gelatin both supported brain cell adhesion and growth for 16days
      in vitro. Cellulose microfiber/gelatin composites containing up to 75% cellulose
      fibers can withstand a higher mechanical load than gelatin alone, and composites
      also provided linear pathways along which brain cells could grow compared to more
      clumped cell growth in gelatin alone. Therefore, the bulk cellulose microfiber
      provides a novel skeleton in this new scaffold material. Cellulose fiber/gelatin
      scaffold supported hMSCs growth and extracellular matrix formation. hMSCs
      osteogenic and adipogenic assays indicated that hMSCs cultured in cellulose
      fiber/gelatin composite preserved the multilineage differentiation potential. As
      natural, biocompatible components, the combination of gelatin and cellulose
      microfibers, fabricated into 3-D matrices, may therefore provide optimal porosity
      and tensile strength for long-term maintenance and observation of cells.

PMID- 20035907
TI  - Electrospun hyaluronate-collagen nanofibrous matrix and the effects of varying
      the concentration of hyaluronate on the characteristics of foreskin fibroblast
      cells.
AB  - In this study we propose a novel electrospinning fabrication process for the
      production of a nanofibrous matrix composed of collagen and hyaluronate. This
      procedure utilized 1,1,1,3,3,3-hexafluoro-2-propanol and formic acid as a mixed
      solvent. Fluorescence microscopy photographs revealed that the resulting
      electrospun nanofibers contained both collagen and hyaluronate. The mean diameter
      of the composite nanofibrous matrix (as observed using scanning electron
      micrographs) was approximately 200nm; this dimension is similar to that of native
      fibrous protein within the extracellular matrix. The expression of proteinases
      (e.g. matrix metalloproteinases, MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) have been implicated in epidermal repair during wound
      healing. Moreover, the characteristics of scarless wounds are known to be related
      to a decreased ratio of TIMP to MMP expression. In the present study the ratio of
      expression of TIMP1 to MMP1 was lower in foreskin fibroblast cells that were
      cultured on a hyaluronate-collagen composite nanofibrous matrix than in those
      cultured on an exclusively collagen nanofibrous matrix. This indicates that the
      hyaluronate-collagen composite nanofibrous matrix could potentially be used as a
      wound dressing for the regeneration of scarless skin.

PMID- 20035908
TI  - The effect of Na(2)CO(3), NaF and NH(4)OH on the stability and release behavior
      of sol-gel derived silica xerogels embedded with bioactive compounds.
AB  - Stability, defined as the reproducible behavior of a device upon its storage, is
      an important issue in pharmaceutical formulation. Silica xerogels obtained
      through the sol-gel route are relatively new as matrices for the controlled
      release of drugs. In some cases, it was observed that their behavior changes upon
      storage, so that they cannot always be defined as "stable". This occurs
      especially when gel processing is performed at mild temperatures, a procedure
      that may have to be used to prevent degradation of the embedded drug. This work
      investigated the use of inorganic catalysts as potential xerogel stability
      inducers when gel curing by heating is not applicable. Three compounds known to
      accelerate sol-gel polymerization, namely ammonia, sodium fluoride and sodium
      carbonate, were introduced during the polymerization of low-temperature processed
      inorganic and organically modified gels, and the effect of each compound on
      xerogel stability and drug release was monitored. The use of carbonate leads to
      formulations with good retention properties, as opposed to ammonia and NaF, which
      lead to poorly retentive xerogels in accordance with their known ability to
      increase porosity. Ammonia was shown to be a poor stability promoter
      independently of gel composition, as opposed to fluoride and carbonate, which
      both displayed stabilizing properties in a dose-dependent manner. No correlation
      was found between xerogel stability and drug release properties. An attempt was
      also made to correlate stability data with polymerization rates and wet gel
      syneresis time evolution with the purpose of identifying one or more synthesis
      parameters that could act as stability predictors for pre-formulation studies. No
      correlation was found between stability and syneresis data. A similar trend in
      the curve of gel time vs. catalyst concentration was observed for the two
      stabilizing catalysts, which was different for the non-stabilizing ammonia. It
      was concluded that the trend of this curve could potentially provide an indicator
      of catalyst stabilizing efficacy.

PMID- 20035909
TI  - When a Picasso is a "Picasso": the entry point in the identification of visual
      art.
AB  - We investigated whether art is distinguished from other real world objects in
      human cognition, in that art allows for a special memorial representation and
      identification based on artists' specific stylistic appearances. Testing art
      experienced viewers, converging empirical evidence from three experiments, which
      have proved sensitive to addressing the question of initial object recognition,
      suggest that identification of visual art is at the subordinate level of the
      producing artist. Specifically, in a free naming task it was found that art
      objects as opposed to non-art-objects were most frequently named with subordinate
      level categories, with the artist's name as the most frequent category
      (Experiment 1). In a category-verification task (Experiment 2), art-objects were
      recognized faster than non-art-objects on the subordinate level with the artist's
      name. In a conceptual priming task, subordinate primes of artists' names
      facilitated matching responses to art-objects but subordinate primes did not
      facilitate responses to non-art-objects (Experiment 3). Collectively, these
      results suggest that the artist's name has a special status in the memorial
      representation of visual art and serves as a predominant entry point in
      recognition in art perception.

PMID- 20035910
TI  - Eszopiclone improves insomnia and depressive and anxious symptoms in
      perimenopausal and postmenopausal women with hot flashes: a randomized, double
      blinded, placebo-controlled crossover trial.
AB  - OBJECTIVE: Menopause-associated insomnia is commonly associated with other
      symptoms (hot flashes, depression, anxiety). Given frequent symptom cooccurrence,
      therapies targeting sleep may provide an important approach to treatment during
      midlife. STUDY DESIGN: Peri/postmenopausal women (40-65 years old) with sleep
      onset and/or sleep-maintenance insomnia cooccurring with hot flashes and
      depressive and/or anxiety symptoms were randomized to eszopiclone 3 mg orally or
      placebo in a double-blinded, crossover 11 week trial. Changes in the Insomnia
      Severity Index (ISI) scale and secondary outcomes (diary-based sleep parameters,
      depression/anxiety, hot flashes, quality of life) were analyzed using repeated
      measure linear models. RESULTS: Of 59 women, 46 (78%) completed the study.
      Eszopiclone reduced ISI scores by 8.7 + or - 1.4 more points than placebo (P <
      .0001). Eszopiclone improved (P < .05) all sleep parameters, depressive symptoms,
      anxiety symptoms, quality of life, and nighttime but not daytime hot flashes.
      CONCLUSION: Eszopiclone treats insomnia and cooccurring menopause-related
      symptoms. Our results provide evidence that hypnotic therapies may improve
      multiple domains of well-being during midlife.

PMID- 20035911
TI  - Herbal use before and during pregnancy.
AB  - OBJECTIVE: We estimated the prevalence and patterns of herbal use among US women
      before and during pregnancy. STUDY DESIGN: The National Birth Defects Prevention
      Study is an ongoing, population-based, case-control study. This analysis included
      4239 women from 10 centers in the United States who delivered infants without
      major birth defects from 1998-2004. RESULTS: The prevalence of reported herbal
      use 3 months before or during pregnancy was 10.9%. During pregnancy, prevalence
      was 9.4% and was highest in the first trimester. Higher prevalence was associated
      with age greater than 30 years and education greater than 12 years. Use varied
      considerably by state (5-17%). Ginger and ephedra were the most commonly reported
      products early in pregnancy; teas and chamomile were most commonly reported
      throughout pregnancy. CONCLUSION: Potentially 395,000 US births annually involve
      antenatal exposure to herbal products. Health care providers should inquire
      routinely about herbal use and educate patients about what little is known
      regarding risks of these products.

PMID- 20035912
TI  - Metformin regresses endometriotic implants in rats by improving implant levels of
      superoxide dismutase, vascular endothelial growth factor, tissue inhibitor of
      metalloproteinase-2, and matrix metalloproteinase-9.
AB  - OBJECTIVE: We sought to test if metformin could regress endometriotic explants in
      rats. STUDY DESIGN: After inducing endometriotic implants and randomization of
      female Wistar albino rats, they were given 25 and 50 mg/kg/day of oral metformin
      in group A (n = 9) and B (n = 8), respectively, for 28 days. Group C (n = 9) was
      given saline as placebo. RESULTS: Mean volume, weight, and histologic score of
      implants in groups A (P < .01, P < .05, and P < .05, respectively) and B (P <
      .01, P < .05, and P < .05, respectively) were significantly lower than in group
      C. The activity of superoxide dismutase and tissue inhibitor of metalloproteinase
      2 staining in groups A (P < .05 and P < .01, respectively) and B (P < .01 and P <
      .01, respectively) was significantly higher than in the control group. Moreover,
      there were more significant reductions in implant levels of vascular endothelial
      growth factor and matrix metalloproteinase-9 in groups A (both P < .001) and B
      (both P < .001) than in group C. CONCLUSION: Metformin causes regression of
      endometriotic implants in rats.

PMID- 20035913
TI  - Multipotent mesenchymal stem cells from human placenta: critical parameters for
      isolation and maintenance of stemness after isolation.
AB  - OBJECTIVE: This study was undertaken to isolate and characterize multipotent
      mesenchymal stem cells from term human placenta (placenta-derived mesenchymal
      stem cells, PD-MSCs). STUDY DESIGN: Sequential enzymatic digestion was used to
      isolate PD-MSCs in which trypsin removes the trophoblast layer, followed by
      collagenase treatment of remaining placental tissue. Karyotype, phenotype, growth
      kinetics, and differentiability of PD-MSC isolates from collagenase digests were
      analyzed. RESULTS: PD-MSC isolation was successful in 14 of 17 cases. Karyotyping
      of PD-MSC isolates from deliveries with a male fetus revealed that these cells
      are of maternal origin. Flow cytometry and immunocytochemistry confirmed the
      mesenchymal stem cell phenotype. Proliferation rates of PD-MSCs remained
      constantly high up to passage 20. These cells could be differentiated toward
      mesodermal lineage in vitro up to passage 20. Nonconfluent culture was critical
      to maintain the MSC stemness during long-term culture. CONCLUSION: Term placenta
      constitutes a rich, very reliable source of maternal mesenchymal stem cells that
      remain differentiable, even at high passage numbers.

PMID- 20035914
TI  - A systematic technique using 3-dimensional ultrasound provides a simple and
      reproducible mode to evaluate the corpus callosum.
AB  - OBJECTIVE: The aim of this study was to evaluate a rapid 3-dimensional ultrasound
      assisted technique for evaluation of the corpus callosum as an integral part of
      the anatomic survey. STUDY DESIGN: Transabdominal 3-dimensioal gray scale and
      power Doppler volumes of the fetal brain were acquired in 102 consecutive healthy
      fetuses at 20-23 postmenstrual weeks. Offline analysis was performed by 2 of the
      authors using a systematic approach of "volume manipulation." Diagnostic-quality
      visualization of the corpus callosum and the pericallosal arteries on the median
      plane was recorded by the 2 examiners independently. RESULTS: The median plane
      was easily obtained in all cases. Diagnostic-quality images of the corpus
      callosum were recorded in 93.1% and 99.0% and of the pericallosal arteries in
      94.4% and 95.5% of the cases, by the 2 examiners, respectively. CONCLUSION: Three
      dimensional ultrasound enables a rapid and easy evaluation of the corpus callosum
      that may facilitate its inclusion as an integral part of the routine anatomic
      survey.

PMID- 20035915
TI  - Albumin as an adjunct to tracheal occlusion in fetal rats with congenital
      diaphragmatic hernia: a placebo-controlled study.
AB  - OBJECTIVE: We sought to investigate effects of intratracheal albumin injection
      prior to tracheal occlusion (TO) on lung proliferation in fetal rats with
      nitrofen-induced congenital diaphragmatic hernia. STUDY DESIGN: On embryonic day
      19, nitrofen-exposed fetuses underwent TO, TO and 50 microL of either
      intratracheal albumin 20% or saline, or remained untouched. Main outcome at
      embryonic day 21.5 was expression of the proliferation marker Ki-67. Secondary
      outcomes were lung-to-bodyweight ratio (LBWR), tropoelastin expression, density
      and spatial distribution of elastin, pulmonary/alveolar morphometry, and fetal
      survival. RESULTS: TO increased Ki-67 messenger RNA and LBWR. Albumin further
      increased LBWR and density of Ki-67-positive cells but also fetal mortality. TO
      with or without adjuncts induced elastin deposits at the tips of arising
      secondary crests, increased air space size, and decreased septal thickness.
      CONCLUSION: TO had effects on lung proliferation and advanced the morphologic
      appearance. Addition of albumin increased density of proliferating cells and
      LBWR, yet at the expense of additional fetal loss.

PMID- 20035916
TI  - Effect of corticosteroids and progesterone on adrenomedullin output and
      expression in human fetal membranes and placenta trophoblasts.
AB  - OBJECTIVE: Plasma adrenomedullin (AM) concentrations are increased in fetal and
      maternal circulation in response to exogenous glucocorticoids administration. The
      role of corticosteroids and progesterone in regulating AM synthesis and secretion
      was investigated in amnion and chorion trophoblast cells of the fetal membranes
      and in placental trophoblast cells. STUDY DESIGN: Cells were treated with
      betamethasone, hydrocortisone, and progesterone. Changes in AM output were
      measured with radioimmunoassay. Protein expression was evaluated with Western
      blot and immunohistochemistry. RESULTS: Betamethasone stimulated AM secretion and
      protein expression in placental trophoblast cells and in amnion cells of the
      fetal membranes. Hydrocortisone and progesterone did not induce any effect either
      on secretion or protein expression in placenta and fetal membranes cells.
      CONCLUSION: Glucocorticoids regulate AM secretion and expression by human
      placenta thereby promoting increased AM concentration in maternal and fetal
      circulation in circumstances characterized by increased cortisol levels.

PMID- 20035917
TI  - Comparing uterine fibroids treated by myomectomy through traditional laparotomy
      and 2 modified approaches: ultraminilaparotomy and laparoscopically assisted
      ultraminilaparotomy.
AB  - OBJECTIVE: We sought to compare myomectomy performed by laparotomy (LT), and 2
      other modified approaches: ultraminilaparotomy (UMLT) and laparoscopically
      assisted UMLT for uterine fibroids with a size <8 cm and the number <5. STUDY
      DESIGN: A cohort study, including 79 (35.3%) women in the LT group, 71 (31.7%) in
      the UMLT group, and 74 (33.0%) in the laparoscopically assisted UMLT group, was
      conducted. The outcome was measured by comparing surgical parameters, immediate
      postoperative recovery, and therapeutic outcomes. RESULTS: The median follow-up
      was 52 months with similar recurrence rates in the 3 groups. The modified
      approaches had advantages not only in the surgical parameters, but also in
      postoperative recovery, compared to LT (all P < .05). CONCLUSION: UMLT and
      laparoscopically assisted UMLT can be used successfully in place of LT in the
      management of uterine fibroids.

PMID- 20035918
TI  - A unique solution to solve the pending medical school tuition crisis.
AB  - The increasing cost of undergraduate medical education and the decreasing
      availability of financial aid have resulted in the accumulation of a large debt
      for medical students that requires a reasonable solution. After reviewing
      suggested solutions to alleviate medical student debt, we have developed a unique
      proposal. The Strategic Alternative for Funding Education (SAFE) has the
      practicing physician pay for his or her medical school education after completion
      of residency/fellowship over a 10-year time interval when income will likely be
      rising. The amount paid yearly is calculated as a percent of the physician's
      professional income. A strategic alternative for funding education has the
      potential to alleviate the pending crisis in medical student debt, allows medical
      schools to compete for students based on the educational experience offered, and
      allows a student of any socioeconomic status to attend medical school and choose
      a medical specialty based solely on ability and desire.

PMID- 20035920
TI  - The effect of live and web-based education on the accuracy of blood-loss
      estimation in simulated obstetric scenarios.
AB  - OBJECTIVE: Visual estimation of blood loss has been shown to be inaccurate. The
      objective of this study was to evaluate the impact of a didactic training program
      on the accuracy of the estimation of blood loss and to compare the effectiveness
      of training provided by a web-based vs live session. STUDY DESIGN:
      Multidisciplinary labor and delivery unit personnel participated in live or web
      based training. Both sessions comprised a 5-station pretest and posttest. The
      primary outcome was the accuracy of estimated blood loss in the pretest compared
      with the posttest with the use of the Mann-Whitney U test. RESULTS: Among 372
      providers, the median improvement between pre- and posttest results was 34% (95%
      confidence interval, 10-57%; P < .001). This improvement did not differ
      significantly between the live sessions and web-based sessions (4%; 95%
      confidence interval, -10% to 12%). CONCLUSION: Our study supports the use of live
      or web-based training to improve blood loss estimation accuracy.

PMID- 20035921
TI  - Graded classification of fetal heart rate tracings: association with neonatal
      metabolic acidosis and neurologic morbidity.

PMID- 20035922
TI  - Wavefront analysis, contrast sensitivity, and depth of focus after cataract
      surgery with aspherical intraocular lens implantation.
AB  - PURPOSE: To determine whether implantation of an aspherical intraocular lens
      (IOL) results in reduced ocular aberrations and improved contrast sensitivity
      after cataract surgery without critical reduction of depth of focus. DESIGN:
      Double-blinded, randomized, prospective study. METHODS: In an intraindividual
      study of 25 patients with bilateral cataract, an aspherical IOL (Akreos Advanced
      Optic [AO]; Bausch & Lomb, Inc., Rochester, New York, USA) was implanted in one
      eye and a spherical IOL (Akreos Fit; Bausch & Lomb, Inc) in the fellow eye.
      Higher-order aberrations with a 5- and 6-mm pupil were measured with a dynamic
      retinoscopy aberrometer at 1 and 3 months after surgery. Uncorrected and best
      corrected visual acuity and contrast sensitivity under mesopic and photopic
      conditions also were measured. Distance-corrected near and intermediate visual
      acuity were studied as a measurement of depth of focus. RESULTS: There was no
      statistically significant difference between eyes in uncorrected and best
      corrected visual acuity at 1 and 3 months after surgery. There was a
      statistically significant between-group difference in contrast sensitivity under
      photopic conditions at 12 cycles per degree and under mesopic conditions at all
      spatial frequencies. The Akreos AO group obtained statistically significant lower
      values of higher-order aberrations and spherical aberration with 5- and 6-mm
      pupils compared with the Akreos Fit group (P < .05). There was no significant
      difference in distance-corrected near and intermediate visual acuity between both
      groups. CONCLUSIONS: Aspherical aberration-free Akreos AO IOL induced
      significantly less higher-order aberrations and spherical aberration than the
      Akreos Fit. Contrast sensitivity was better under mesopic conditions with the
      Akreos AO with similar results of depth of focus.

PMID- 20035923
TI  - Long-term follow-up of full macular translocation for choroidal
      neovascularization.
AB  - PURPOSE: To report the long-term (>5 years) results of full macular translocation
      in patients with choroidal neovascularization (CNV). DESIGN: Retrospective,
      interventional case series. METHODS: This study involved 32 eyes of 32 patients
      who had undergone full macular translocation for CNV. The median follow-up was
      6.5 years (range, 5.2 to 7.7 years). We evaluated the best-corrected visual
      acuity, fundus examination results obtained before and 1 and 5 years after
      operation, and postoperative complications. RESULTS: At the 1-year follow-up,
      foveal retinal pigment epithelium atrophy was observed in only 3 eyes (12%), and
      the mean logarithm of the minimal angle of resolution (logMAR) visual acuity (VA)
      at that time (1.39 +/- 0.67) was not significantly changed from that before
      surgery (logMAR, 1.31 +/- 0.66) in 25 eyes with age-related macular degeneration
      (AMD). However, at 5-year follow-up, foveal retinal pigment epithelium atrophy
      increased (18 eyes; 72%), and final mean logMAR VA (1.88 +/- 0.76) was
      significantly lower (P < .01). Five eyes with myopic CNV maintained their VA from
      before operation (mean logMAR, 0.88 +/- 0.35) until final follow-up (mean logMAR,
      0.73 +/- 0.31). The final VA was significantly better in myopic CNV than in
      exudative age-related macular degeneration on multiple regression analysis (P =
      .019). CONCLUSIONS: Long-term follow-up of full macular translocation showed that
      the final VA was poor in age-related macular degeneration, but relatively better
      in myopic CNV.

PMID- 20035925
TI  - Imbalance of oxidative/anti-oxidative status induced by periodontitis is involved
      in apoptosis of rat submandibular glands.
AB  - OBJECTIVE: Epidemiologic studies suggest a relationship between periodontitis and
      salivary gland dysfunction. A rat periodontitis model was used to investigate
      whether a causal relationship exists between periodontitis and pathological
      changes of submandibular glands. DESIGN: Fourteen male Wistar rats (8 weeks old)
      were divided into two groups (n=7/group): a control group and periodontitis
      group. Periodontitis was induced by ligature placement around the mandibular
      first molars. Serum levels for reactive oxygen metabolites, anti-oxidant and
      tumour necrosis factor (TNF)-alpha were measured at baseline, 2 and 4 weeks. At 4
      weeks, the levels of 8-hydroxydeoxyguanosine were determined to evaluate
      oxidative damage of submandibular glands. Expression of TNF-alpha mRNA and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) as
      well as histological findings were also evaluated in the submandibular glands.
      RESULTS: The rats with experimental periodontitis showed increase in the levels
      of serum reactive oxygen metabolites and TNF-alpha, and a decrease of anti
      oxidant power in a time-dependent manner. At 4 weeks, these rats also had
      significantly increased levels of 8-hydroxydeoxyguanosine and TNF-alpha, and
      increased number of TUNEL-positive cells and vacuolisation in the submandibular
      glands compared to the control rats. CONCLUSIONS: Imbalance of circulating
      oxidative/anti-oxidative status may be involved in vacuolisation and apoptosis of
      submandibular glands in the rat periodontitis model.

PMID- 20035924
TI  - A simplified quantitative method for assessing keratoconjunctivitis sicca from
      the Sjogren's Syndrome International Registry.
AB  - PURPOSE: To describe, apply, and test a new ocular grading system for assessing
      keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein. DESIGN:
      Prospective, observational, multicenter cohort study. METHODS: The National
      Institutes of Health-funded Sjogren's Syndrome International Registry (called
      Sjogren's International Collaborative Clinical Alliance [SICCA]) is developing
      standardized classification criteria for Sjogren syndrome (SS) and is creating a
      biospecimen bank for future research. Eight SICCA ophthalmologists developed a
      new quantitative ocular grading system (SICCA ocular staining score [OSS]), and
      we analyzed OSS distribution among the SICCA cohort and its association with
      other phenotypic characteristics of SS. The SICCA cohort includes participants
      ranging from possibly early SS to advanced disease. Procedures include sequenced
      unanesthetized Schirmer test, tear break-up time, ocular surface staining, and
      external eye examination at the slit lamp. Using statistical analyses and
      proportional Venn diagrams, we examined interrelationships between abnormal OSS
      (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with
      focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies,
      anti-SS B antibodies, or both). RESULTS: Among 1208 participants, we found strong
      associations between abnormal OSS, positive serologic results, and positive LSG
      focus scores (P < .0001). Analysis of the overlapping relationships of these 3
      measures defined a large group of participants who had KCS without other
      components of SS, representing a clinical entity distinct from the KCS associated
      with SS. CONCLUSIONS: This new method for assessing KCS will become the means for
      diagnosing the ocular component of SS in future classification criteria. We find
      2 forms of KCS whose causes may differ.

PMID- 20035927
TI  - Betrayal: a psychological analysis.
AB  - Betrayal is the sense of being harmed by the intentional actions or omissions of
      a trusted person. The most common forms of betrayal are harmful disclosures of
      confidential information, disloyalty, infidelity, dishonesty. They can be
      traumatic and cause considerable distress. The effects of betrayal include shock,
      loss and grief, morbid pre-occupation, damaged self-esteem, self-doubting, anger.
      Not infrequently they produce life-altering changes. The effects of a
      catastrophic betrayal are most relevant for anxiety disorders, and OC D and PTSD
      in particular. Betrayal can cause mental contamination, and the betrayer commonly
      becomes a source of contamination. In a series of experiments it was demonstrated
      that feelings of mental contamination can be aroused by imagining unacceptable
      non-consensual acts. The magnitude of the mental contamination was boosted by the
      introduction of betrayal themes. Feelings of mental contamination can also be
      aroused in some 'perpetrators' of non-consensual acts involving betrayal. The
      psychological significance of acts of betrayal is discussed.

PMID- 20035926
TI  - HIV protease inhibitors block oral epithelial cell DNA synthesis.
AB  - OBJECTIVES: Anti-retroviral therapy regimens that include HIV protease inhibitors
      (PIs) are associated with diverse adverse effects including increased prevalence
      of oral warts, oral sensorial deficits and gastrointestinal toxicities suggesting
      that PIs may perturb epithelial cell biology. To test the hypothesis that PIs
      could affect specific biological processes of oral epithelium, the effects of
      these agents were evaluated in several oral epithelial cell-lines. DESIGN:
      Primary and immortalized oral keratinocytes and squamous carcinoma cells of
      oropharyngeal origin were cultured in the presence of pharmacologically relevant
      concentrations of PIs. Their affects on cell viability, cytotoxicity and DNA
      synthesis were assessed by enzymatic assays and incorporation of 5-bromo-2'
      deoxyuridine (BrdU) into DNA. RESULTS: Viability of primary and immortalized oral
      keratinocytes as well as squamous carcinoma cells of oropharyngeal origin was
      significantly reduced by select PIs at concentrations found in plasma. Of the
      seven PIs evaluated, nelfinavir was the most potent with a mean 50% inhibitory
      concentration [IC(50)] of 4.1 microM. Lopinavir and saquinavir also reduced
      epithelial cell viability (IC(50) of 10-20 microM). Atazanavir and ritonovir
      caused minor reductions in viability, while amprenavir and indinavir were not
      significant inhibitors. The reduced cell viability, as shown by BrdU
      incorporation assays, was due to inhibition of DNA synthesis rather than cell
      death due to cytotoxicity. CONCLUSION: Select PIs retard oral epithelial cell
      proliferation in a drug and dose-dependent manner by blocking DNA synthesis. This
      could account for some of their adverse effects on oral health.

PMID- 20035928
TI  - An approach to stereoselective preparation of 3-C-glycosylated D- and L-glucals.
AB  - An approach to stereoselective synthesis of alpha- or beta-3-C-glycosylated L- or
      D-1,2-glucals starting from the corresponding alpha- or beta
      glycopyranosylethanals is described. The key step of the approach is the
      stereoselective cycloaddition of chiral vinyl ethers derived from both
      enantiomers of mandelic acid. The preparation of 1,5-anhydro-4,6-di-O-benzyl-2,3
      dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl-beta-D-glucopyranosyl)methyl]-L-arabino-hex
      1-enitol, 1,5-anhydro-4,6-di-O-benzyl-2,3-dideoxy-3-C-[(2,3,4,6-tetra-O-benzyl
      beta-D-glucopyranosyl)methyl]-D-arabino-hex-1-enitol, and 1,5-anhydro-4,6-di-O
      benzyl-2,3-dideoxy-3-C-[(2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl)methyl]-D
      arabino-hex-1-enitol serves as an example of this approach.

PMID- 20035929
TI  - Synthesis, characterization, and cytotoxicity of some novel glycosyl thiazol-2
      imines as antitumoral agents.
AB  - A series of novel glycosyl thiazol-2-imines (3a-g) have been synthesized
      regioselectively in good yields from the hydrolysis of thiazol-2(3H)-imine-linked
      glycoconjugates. The glycosyl thiazol-2-imines were evaluated for their antitumor
      activity against Hela (cervical carcinoma), HCT-8 (colon carcinoma) and Bel-7402
      (liver carcinoma). Among the compounds screened, 1-benzoyl-4-(4-nitrophenyl)-3
      beta-D-glucopyranosyl-thiazol-2(3H)-imine (3c) was found to be the most active
      compound against HCT-8.

PMID- 20035930
TI  - Synthesis of a tetrasaccharide related to the O-antigen from Azospirillum
      lipoferum SR65.
AB  - Concise synthesis of a tetrasaccharide repeating unit of the LPS isolated from
      Azospirillum lipoferum SR65 has been accomplished through suitable protecting
      group manipulations and stereoselective glycosylation starting from commercially
      available L-rhamnose and D-glucose. The target oligosaccharide in the form of its
      p-methoxyphenyl glycoside is suitable for further glycoconjugate formation via
      selective cleavage of the OMP glycoside. Plant growth-promoting bacteria (PGPB)
      of genus Azospirillum plays important roles in the growth and development of
      plants. The interaction between the roots of the plants and the microbes is
      governed by the cell surface carbohydrate polymers (CPS, LPS, etc.). The present
      synthetic-based study elucidates aspects of plant-microbe interaction and future
      biofertiliser design.

PMID- 20035932
TI  - The role of activation-induced cell death in the higher onset of spontaneous
      apoptosis of NK cell subsets in patients with metastatic epithelial cancer.
AB  - To address the question whether the higher onset of apoptosis of circulating NK
      cell subsets might be activation induced in cancer patients, surface expression
      of NKG2D and serum (s) levels of MHC class I chain-related (MIC) proteins in
      relation to apoptosis marker and CD95 expression on NK cells were evaluated.
      Patients showed a significantly higher onset of spontaneous apoptosis of CD56dim
      NK cells. No difference in the CD95 expression could be detected between patients
      and normal controls (NCs). Patients' CD56bright NK cells demonstrated a higher
      expression of NKG2D compared to CD56dim NK cells. The sMICB levels showed a
      higher level in patients versus NCs. No correlation between sMIC protein levels
      with both NKG2D expression and onset of spontaneous apoptosis of NK cell subsets
      was found. Our data suggest that the higher onset of apoptosis of circulating NK
      cell subsets of patients is not triggered by activation-induced cell death.

PMID- 20035933
TI  - Rescuing stimuli from invisibility: Inducing a momentary release from visual
      masking with pre-target entrainment.
AB  - At near-threshold levels of stimulation, identical stimulus parameters can result
      in very different phenomenal experiences. Can we manipulate which stimuli reach
      consciousness? Here we show that consciousness of otherwise masked stimuli can be
      experimentally induced by sensory entrainment. We preceded a backward-masked
      stimulus with a series of rapid visual events presented at 12 Hz for 800 ms.
      Peaks in visual sensitivity (d') were observed when the target appeared at the
      time that the next entraining stimuli would have occurred. Observers' sensitivity
      for identical masked near-threshold stimuli increased by factors as large as 55%,
      but only at this precise moment in time. These data thus reveal that awareness of
      near-threshold stimuli can be manipulated by entrainment to rhythmic events,
      supporting the functional role of induced oscillations in underlying cortical
      excitability, and suggest a plausible mechanism of temporal attention.

PMID- 20035931
TI  - Thymic nurse cells exhibit epithelial progenitor phenotype and create unique
      extra-cytoplasmic membrane space for thymocyte selection.
AB  - Thymic nurse cells (TNCs) are epithelial cells in the thymic cortex that contain
      as many as 50 thymocytes within specialized cytoplasmic vacuoles. The function of
      this cell-in-cell interaction has created controversy since their discovery in
      1980. Further, some skepticism exists about the idea that apoptotic thymocytes
      within the TNC complex result from negative selection, a process believed to
      occur exclusively within the medulla. In this report, we have microscopic
      evidence that defines a unique membranous environment wherein lipid raft
      aggregates around the alphabetaTCR expressed on captured thymocytes and class II
      MHC molecules expressed on TNCs. Further, immunohistological examination of
      thymic sections show TNCs located within the cortico-medullary junction to
      express cytokeratins five and eight (K5 and K8), and the transcription factor Trp
      63, the phenotype defined elsewhere as the thymic epithelial progenitor subset.
      Our results suggest that the microenvironment provided by TNCs plays an important
      role in thymocyte selection as well as the potential for TNCs to be involved in
      the maintenance of thymic epithelia.

PMID- 20035934
TI  - Subject relative clauses are not universally easier to process: Evidence from
      Basque.
AB  - Studies from many languages consistently report that subject relative clauses
      (SR) are easier to process than object relatives (OR). However, Hsiao and Gibson
      (2003) report an OR preference for Chinese, a finding that has been contested.
      Here we report faster OR versus SR processing in Basque, an ergative, head-final
      language with pre-nominal relative clauses. A self-paced reading task was used in
      Experiments 1 and 2, while ERPs were recorded in Experiment 3. We used relative
      clauses that were ambiguous between an object or subject-gap interpretation and
      disambiguated later in the sentence. The results of Experiments 1 and 2 showed
      that SR took longer to read than OR in the critical disambiguating region. In
      addition, Experiment 3 showed that SR produced larger amplitudes than OR in the
      P600 window immediately after reading the critical disambiguating word. Our
      results suggest that SR are not universally easier to process. They cast doubts
      on universal hypotheses and suggest that processing complexity may depend on
      language-specific aspects of grammar.

PMID- 20035936
TI  - Different stabilisation techniques for typical acetabular fractures in the
      elderly--a biomechanical assessment.
AB  - OBJECTIVES: The tremendous increase of acetabular fractures in the elderly
      provides new challenges for their surgical treatment. The aim of this study was
      to evaluate the biomechanical properties of conventional and newly developed
      implants for the stabilisation of an anterior column combined with posterior
      hemitransverse fracture (ACPHTF), which represents the typical acetabular
      fracture in the elderly. METHODS: Using a single-leg stance model we analysed
      four different implant systems for the stabilisation of ACPHTFs in synthetic and
      cadaveric pelvises. Applying an increasing axial load, fracture dislocation was
      analysed with a new multidirectional ultrasonic measuring system. Results of the
      different implant systems were compared by Scheffe post hoc test and one-way
      ANOVA. RESULTS: In synthetic pelvises, the standard reconstruction plate fixed by
      3 periarticular long screws and a new titanium fixator with multidirectional
      interlocking screws were associated with significantly less dislocation of the
      fractured quadrilateral plate of the acetabulum when compared to a standard
      reconstruction plate fixed by only one periarticular long screw and a locking
      reconstruction plate. No significant differences between the different
      osteosynthesis techniques could be observed in cadaver pelvises, probably due to
      a heterogeneous bone quality. CONCLUSIONS: We conclude that the plate fixation by
      positioning of periarticular long screws as well as the multidirectional
      positioning of interlocking screws account for the most sufficient fracture
      stabilisation of ACPHTFs under experimental conditions.

PMID- 20035935
TI  - A novel nano-composite multi-layered biomaterial for treatment of osteochondral
      lesions: technique note and an early stability pilot clinical trial.
AB  - INTRODUCTION: Osteochondral articular defects are a key concern in orthopaedic
      surgery. Current surgical techniques to repair osteochondral defects lead to poor
      subchondral bone regeneration and fibrocartilage formation, which is often
      associated with joint pain and stiffness. The objective of this pilot clinical
      study is to evaluate the performance and the intrinsic stability of a newly
      developed biomimetic osteochondral scaffold and to test the safety and the
      feasibility of the surgical procedure. METHODS: A gradient composite
      osteochondral scaffold based on type I collagen-hydroxyapatite was obtained by
      nucleating collagen fibrils with hydroxyapatite nanoparticles. Thirteen patients
      (15 defect sites) were treated with scaffold implantation from January 2007 to
      July 2007: four at the medial femoral condyle, two at the lateral femoral
      condyles, five at the patellas and four at the trochleas. The mean size of the
      defects was 2.8 cm(2) (range: 1.5-5.9 cm(2)). All patients were followed up
      prospectively. High-resolution magnetic resonance imaging (MRI) was used to
      determine "the early postoperative adherence rate" at 4-5 weeks and 25-26 weeks
      after scaffold implantation. Moreover, the magnetic resonance observation of
      cartilage repair tissue (MOCART) score was performed on every MRI. Two second
      looks were performed at 6 months; cartilage repair was assessed using the
      International Cartilage Repair Society (ICRS) visual scoring system and
      histological and immunohistochemical analysis of the two biopsies was carried
      out. RESULTS: A completely attached graft and repair tissue were found in 13 of
      15 lesions (86.7%). A partial detachment was observed in two patients (13.3%). No
      detached grafts were found. Complete filling of the cartilage defect and
      congruency of the articular surface were seen in 10 lesions (66.7%) with MRI
      evaluation at 6 months. The complete integration of the grafted cartilage was
      detected in eight lesions (53.3%). Subchondral bone changes (oedema or sclerosis)
      were found in eight defects (53.3%). Statistical analysis showed a significant
      improvement in the International Knee Documentation Committee (IKDC) subjective
      and objective scores from preoperative to 6 months' follow-up (p<0.0005). Visual
      scoring of the repaired tissue at second-look revealed a normal repair score in
      one case and a near-normal repair score in the other case. Histological analysis
      showed the formation of subchondral bone without the presence of biomaterial. The
      cartilage repair tissue appeared to be engaged in an ongoing maturation process.
      CONCLUSIONS: The technique is safe and MRI evaluation at short-term follow-up has
      demonstrated good stability of the scaffold without any other fixation device.
      The preliminary clinical results at short-term follow-up are encouraging. A
      clinical and MRI study with longer follow-up and randomised studies will be done
      to confirm the high potential of this novel osteochondral scaffold.

PMID- 20035937
TI  - Management of late-diagnosed scaphoid fractures.
AB  - BACKGROUND: Scaphoid fractures are among the most common types of carpal bone
      injury; they can be easily overlooked in the acute stage. Scaphoid fractures
      detected in the subacute stage require a more meticulous and prompt approach, to
      prevent chronicity and regain wrist function. METHODS: The records of 30 patients
      were selected from 97 with scaphoid fractures surgically treated between 1994 and
      2002. Fractures that were diagnosed between 2 weeks and 5 months (average, 2.2
      months) after the injury were included. We report the fracture patterns and
      locations, as determined from radiographs, as well as the surgical methods used.
      The mean follow-up was 2.5 years. RESULTS: Oblique fractures (60%) were the most
      commonly overlooked fractures. Twenty-six patients (87%) underwent open surgery,
      and 23 (77%) required bone grafts. Percutaneous fixation was indicated for only
      four patients, whose fractures were reducible via either fluoroscopic or
      arthroscopic guidance. Osseous unions were achieved for 29 (97%) patients; these
      patients returned to their pre-injury level of activity. The average union time
      was 10.6 weeks. CONCLUSION: Oblique-type scaphoid fractures are potentially
      unstable and may result in detrimental sequelae if overlooked in the acute stage.
      Accurate diagnosis is possible through critical skepticism and the meticulous
      scrutiny of radiographs. Prompt surgical intervention is associated with
      promising outcomes.

PMID- 20035938
TI  - Costs of post-abortion care in low- and middle-income countries.
AB  - OBJECTIVE: To evaluate the quality of costing studies of post-abortion care from
      low- and middle-income countries and to describe costs in various settings.
      METHODS: A systematic review identified unit costs. Descriptive statistical
      analysis and univariate regression analysis identified drivers of unit costs of
      post-abortion care. RESULTS: There are few cost studies from Asia or Eastern
      Europe. Data indicate that the cost (in 2007 international dollars) of post
      abortion care in Africa and Latin America is $392 and $430, respectively, per
      case. CONCLUSION: Differences in post-abortion care costs were associated with
      region, procedure, facility level, case severity, and whether the study was
      operations research. Methods varied between studies, and efforts should be made
      in future research to improve consistency. Additional data are needed from Asia
      and Eastern Europe, as well as the costs of medical methods of uterine
      evacuation. These data justify improved access to contraception and safe, legal
      abortion.

PMID- 20035939
TI  - The risk of the metabolic syndrome on carotid thickness and stiffness: sex and
      age specific effects.
AB  - BACKGROUND AND PURPOSE: The metabolic syndrome (MS) is associated with a high
      risk for cardiovascular disease. Intima-media thickness (IMT) and stiffness
      reflect structure and functional alterations in arteries. We investigated the
      relationship of MS on IMT and stiffness and also dissected its gender and age
      specific effect. METHODS: Carotid segment-specific IMT and stiffness were
      obtained in 1245 stroke- and myocardial infarction free volunteers between the
      ages of 15 and 87. The MS was defined according to the National Cholesterol
      Education Program Adult Treatment Panel III with Asian modification. RESULTS: The
      prevalence of MS was 22.2% in our study population. The MS was associated with
      increased IMT in the common carotid artery (CCA IMT) and stiffness modalities
      (including Ep, beta, and PWV), but was not associated with bifurcation and
      internal carotid artery IMT. The relationship of MS on atherosclerosis was more
      prominent in women than in men. Only women revealed a significant interaction
      between MS and age for CCA IMT (p=0.013), which was more pronounced in young
      women (< or = 45 years) than in elderly. Comparing the risk components between
      young and elderly women in regard to MS, high triglycerides were more common in
      the affected young women (p=0.007). CONCLUSIONS: MS is associated with a risk for
      increased CCA IMT and stiffness, and this relationship is particularly pronounced
      in women. Age can modify the MS impact on atherosclerosis. Young women with MS
      who often have high triglycerides experience the highest risk to associate with
      atherosclerosis. Young MS women who are easily overlooked for atherosclerotic
      diseases need more detailed assessment for atherosclerosis to prevent premature
      cardiovascular disease.

PMID- 20035941
TI  - In vitro model of a semicircular canal: design and validation of the model and
      its use for the study of canalithiasis.
AB  - We present an experimental model for a semicircular canal with canalithiasis.
      Canalithiasis is a pathological condition where free-floating particles disturb
      the flow field in the semicircular canals. It may lead to a specific form of
      vertigo known as BPPV or top-shelf vertigo. A careful scaling of the physical and
      geometrical parameters allows us to study the mechanics of this disease on an
      enlarged model of a single semicircular canal with laser vibrometry and video
      particle tracking. Early results confirm the proper operation of the model canal
      and support the current theories on the mechanisms of BPPV.

PMID- 20035940
TI  - Pharmacological inhibition of BLT1 diminishes early abdominal aneurysm formation.
AB  - Leukotriene B(4) (LTB(4)) is a pro-inflammatory lipid mediator generated by the
      enzymes 5-lipoxygenase (5-LO) and LTA(4)-hydrolase. LTB(4) signals primarily
      through its G protein-coupled receptor BLT1, which is highly expressed on
      specific leukocyte subsets. Recent genetic studies in humans as well as knockout
      studies in mice have implicated the leukotriene synthesis pathway in several
      vascular pathologies. Here we tested the hypothesis that pharmacological
      inhibition of BLT1 diminishes abdominal aortic aneurysm (AAA) formation, a major
      complication associated with atherosclerotic vascular disease. Chow-fed Apoe(-/-)
      mice were treated with a 4-week infusion of Angiotensin II (AngII, 1000 ng/(kg
      min)) beginning at 10 weeks of age, in a well-established murine AAA model.
      Administration of the selective BLT1 antagonist CP-105,696 beginning
      simultaneously with AngII infusion reduced the incidence of AAA formation from
      82% to 40% (p<0.05). There was a concordant reduction in maximal aortic diameter
      from 2.35 mm to 1.56 mm (p<0.05). While administration of the antagonist on day
      14 after the onset of AngII infusion diminished lesional macrophage accumulation,
      it did not significantly alter the size of AAA by day 42. Thus, pharmacological
      inhibition of BLT1 may ultimately hold clinical promise, but early intervention
      may be critical.

PMID- 20035942
TI  - New sorbents for extraction and microextraction techniques.
AB  - This review outlines recent progress in the research on some new classes of
      sorbents for extraction and microextraction techniques. Carbon nanotubes are
      allotropes of carbon with cylindrical structure. They are very stable systems
      having considerable chemical inertness due to the strong covalent bonds of the
      carbon atoms on the nanotube surface. Some applications of carbon nanotubes are
      presented in a perspective view. Molecular imprinting has proved to be an
      effective technique for the creation of recognition sites on a polymer scaffold.
      By a mechanism of molecular recognition, the molecularly imprinted polymers are
      used as selective tools for the development of various analytical techniques such
      as liquid chromatography, capillary electrochromatography, solid-phase extraction
      (SPE), binding assays and biosensors. Sol-gel chemistry provides a convenient
      pathway to create advanced material systems that can be effectively utilized to
      solve the solid phase microextraction fiber technology problems. This review is
      mainly focused on recent advanced developments in the design, synthesis and
      application of sol-gel in preparation of coatings for the SPME fibers.

PMID- 20035943
TI  - Silica encapsulation of n-octadecane via sol-gel process: a novel
      microencapsulated phase-change material with enhanced thermal conductivity and
      performance.
AB  - A novel microencapsulated phase-change material (PCM) based on an n-octadecane
      core and an inorganic silica shell was designed to enhance thermal conductivity
      and phase-change performance. These silica microcapsules were synthesized by
      using TEOS as an inorganic source through a sol-gel process. Fourier transform
      infrared spectra confirm that the silica shell material was successfully
      fabricated onto the surface of the n-octadecane core. Scanning electronic
      microscopy images suggest that the silica microcapsules exhibit a spherical
      morphology with a well-defined core-shell microstructure. Furthermore, the silica
      microcapsules synthesized at pH 2.45 display a smooth and compact surface. These
      microcapsules also present a large particle size range of 7-16 microm. Wide-angle
      X-ray scattering patterns indicate that the n-octadecane inside the silica
      microcapsules still retains a good crystallinity. Thermogravimetric analysis
      shows that these silica microcapsules are degraded in two distinct steps, and
      have good thermal stability. The silica-microencapsulated n-octadecane can
      achieve good phase-change performance, high encapsulation efficiency, and good
      antiosmosis property by controlling the loading of core material and acidity of
      the reaction solution during the sol-gel process. The thermal conductivity of the
      microencapsulated n-octadecane is also significantly enhanced due to the presence
      of the high thermal conductive silica shell.

PMID- 20035944
TI  - Adsorptive removal of dihydrogenphosphate ion from aqueous solutions using mono,
      di- and tri-ammonium-functionalized SBA-15.
AB  - Adsorption of monovalent phosphate anions from aqueous solutions on mono, di- and
      tri-ammonium-functionalized mesoporous SBA-15 silica was investigated. The
      adsorbent was prepared via a post-synthesis grafting method, using 3
      aminopropyltrimethoxysilane (N-silane), [1-(2-aminoethyl)-3
      aminopropyl]trimethoxysilane (NN-silane) and 1-[3-(trimethoxysilyl)-propyl]
      diethylenetriamine (NNN-silane), followed by acidification in HCl solution to
      convert the attached surface amino groups to positively charged ammonium
      moieties. The loading of amino moieties on the SBA-15 surface was varied from 5%
      to 40% as organoalkoxysilane/silica molar ratio. The adsorption experiments were
      conducted batchwise at room temperature. Results showed that adsorption capacity
      increased with increasing the concentration of functional groups on the SBA-15
      adsorbent whatever the nature of the functional group. In the case of
      monoammonium functional groups, the adsorption capacity increased from 0.64 to
      1.07 mmol H(2)PO(4)(-)/g when the molar ratio organoalkoxysilane/silica was
      varied from 5% to 40%, respectively. Similar tendency was observed in the case of
      diammonium and triammonium organic functional groups. Also, for the same
      organoalkoxysilane/silica molar ratio, the adsorption capacity increased markedly
      with the increase of the number of protonated amines in the functional groups.
      Therefore, maximum adsorption capacities of 1.07, 1.70 and 2.46 mmol H(2)PO(4)(
      )/g adsorbent were obtained using mono-, di- and tri-ammonium-functionalized SBA
      15, respectively.

PMID- 20035945
TI  - A simple method for preparation of Ag nanofilm used as active, stable, and
      biocompatible SERS substrate by using electrostatic self-assembly.
AB  - A new SERS-active Ag nanofilm on the surface of a glass slide has been prepared
      by a low-cost electrochemical strategy using polyvinyl alcohol (PVA) at a proper
      voltage. The two-dimensional morphology of the Ag nanofilm has been examined by
      scanning electron microscopy (SEM). The average size of the aggregated particles
      on the surface of the Ag nanofilm is up to ca. 200+/-50 nm, which is much larger
      than that of PVA-protected Ag colloidal nanoparticles (PVA-Ag CNPs, 45+/-8 nm).
      Meanwhile, many nano-scale regions with average sizes of ca. 300+/-50 nm are
      formed between the adjacent Ag nanoparticles. By the SERS measurements of human
      serum (HS) and hemoglobin (Hb), this Ag nanofilm is shown to be an excellent SERS
      substrate with good stability and biocompatibility. As the fabrication process of
      this SERS substrate is simple and inexpensive, this method may be used in large
      scale preparation of substrates that have been widely applied in Raman analysis.
      In addition, this SERS-active Ag nanofilm can serve as a novel SERS substrate in
      biochemical analysis due to the biocompatibility.

PMID- 20035946
TI  - Electrochemical charge of silica surfaces at high ionic strength in narrow
      channels.
AB  - We present a theoretical framework to calculate the electrochemical charge on
      silica surfaces in contact with high-ionic-strength solutions in narrow channels.
      Analytical results indicate that the contribution of the adsorbed metal cations
      to the total surface charge is not negligible when the salinity is larger than 1
      mM. The electrical triple-layer model is proved much better than other models for
      high ionic strength. The charge regulation caused by the double-layer overlap in
      narrow channels will reduce the surface charge density but increase the zeta
      potential on silica surfaces.

PMID- 20035947
TI  - Leveling of thin films of colloidal suspensions.
AB  - We present an analysis of leveling in thin films of colloidal suspensions. The
      colloidal particles are assumed to be much smaller than the film thickness and
      influence the film rheology through a concentration-dependent viscosity and bulk
      diffusivity. A system of coupled nonlinear partial differential equations based
      on lubrication theory is used to describe the film height and the particle
      concentrations in the bulk and at the film surface. Linear stability analysis is
      applied to develop expressions for leveling rates in a number of limiting cases.
      It is found that for soluble particles, there exist regimes where increasing the
      Marangoni number slows down leveling at both short and long times, in contrast to
      the case of insoluble particles. Nonlinear simulations show that the linear
      theory accurately predicts leveling times even for large amplitude disturbances,
      and that the presence of a concentration-dependent viscosity and bulk diffusivity
      speed up leveling. The results of this work should be useful for estimating
      leveling rates in coatings laden with colloidal particles, and also in coatings
      containing soluble surfactant.

PMID- 20035948
TI  - Monodisperse and fluorescent poly(styrene-co-methacrylic acid-co-2-naphthyl
      methacrylate)/Fe3O4 composite particles.
AB  - This article describes the preparation and characterization of fluorescent and
      magnetic composite particles of poly(styrene-co-methacrylic acid-co-2-naphthyl
      methacrylate) (poly(St/MAA/NMA)). First, monodisperse (D(w)/D(n)<1.1) and
      fluorescent poly(St/MAA/NMA) submicron particles were prepared using emulsifier
      free emulsion polymerization by varying the concentration of the fluorescent
      comonomer, i.e., NMA. Composition of the particles was characterized by (1)H NMR,
      FT-IR, GPC, and DSC analyses. The molecular weights and particle size of the
      particles were dependent on the NMA concentration. Second, Fe(3)O(4)
      nanoparticles were immobilized onto the poly(St/MAA/NMA) submicron particles to
      give rise to multifunctional properties. The morphology and particles size were
      characterized by FE-SEM and CHDF. These poly(St/MAA/NMA)/Fe(3)O(4) composite
      particles exhibited both fluorescent properties under UV irradiation at 365 nm
      and magnetic properties. Photo-luminescent (PL) intensity of the particles showed
      linear dependence with NMA concentration.

PMID- 20035949
TI  - Mechanism of heavy metal uptake by a hybrid MCM-41 material: surface complexation
      and EPR spectroscopic study.
AB  - A novel hybrid MCM-41-based material was synthesized by incorporation of AEDTC [N
      (2-aminoethyl)dithiocarbamate] in the MCM-41 pores. The derived MCM-41 x AEDTC
      material possesses high AEDTC loading 35% [w:w], and a well-defined array of
      regular mesopores with a specific surface area of 632 m(2)/g. Heavy metal, Cd,
      Pb, Cu, and Zn, uptake was studied in detail at physiological pH values 6-8, by a
      combination of analytical and electron paramagnetic resonance (EPR) spectroscopic
      techniques. The analytical data show a significant improvement, i.e., 200-500%,
      for Pb, Cu, and Zn uptake by the MCM-41 x AEDTC hybrid vs the unmodified MCM-41.
      In contrast, Cd shows an exceptional behavior: (a) Cd uptake by MCM-41 x AEDTC is
      very low. (b) Competitive metal uptake experiments reveal that Cd ions cause a
      characteristic inhibition of Cu or Pb uptake by the MCM-41 x AEDTC while Cd
      binding itself always remained low. The present findings are analyzed by a
      combination of surface complexation modeling and EPR spectroscopy. Accordingly,
      in the MCM-41 x AEDTC the sulfur atoms of AEDTC provide strong binding sites for
      metal binding, with a stoichiometry [S(AEDTC)]:[Metal] = 1:1. Cd inhibits
      accessibility of Cu or Pb ions in the AEDTC sites.

PMID- 20035950
TI  - How to increase the accuracy of electrocardiogram's interpretation and stimulate
      the interest of the interpreters?

PMID- 20035951
TI  - Nine times measure, 10th cut away.

PMID- 20035953
TI  - Increased stress reactivity is associated with cognitive deficits and decreased
      hippocampal brain-derived neurotrophic factor in a mouse model of affective
      disorders.
AB  - Cognitive deficits are a common feature of major depression (MD), with largely
      unknown biological underpinnings. In addition to the affective and cognitive
      symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis
      is commonly observed in these patients. Increased plasma glucocorticoid levels
      are known to render the hippocampus susceptible to neuronal damage. This
      structure is important for learning and memory, creating a potential link between
      HPA axis dysregulation and cognitive deficits in depression. In order to further
      elucidate how altered stress responsiveness may contribute to the etiology of MD,
      three mouse lines with high (HR), intermediate (IR), or low (LR) stress
      reactivity were generated by selective breeding. The aim of the present study was
      to investigate whether increased stress reactivity is associated with deficits in
      hippocampus-dependent memory tests. To this end, we subjected mice from the HR,
      IR, and LR breeding lines to tests of recognition memory, spatial memory, and
      depression-like behavior. In addition, measurements of brain-derived neurotrophic
      factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our
      results demonstrate that HR mice exhibit hippocampus-dependent memory deficits
      along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress
      reactivity mouse lines are a promising animal model of the cognitive deficits in
      MD with the unique feature of a genetic predisposition for an altered HPA axis
      reactivity, which provides the opportunity to explore the progression of the
      symptoms of MD, predisposing genetic factors as well as new treatment strategies.

PMID- 20035954
TI  - [The free software in medical research].

PMID- 20035955
TI  - [How can we improve the confidence intervals?].

PMID- 20035952
TI  - Dysfunctional reward processing in male alcoholics: an ERP study during a
      gambling task.
AB  - OBJECTIVE: A dysfunctional neural reward system has been shown to be associated
      with alcoholism. The current study aims to examine reward processing in male
      alcoholics by using event-related potentials (ERPs) as well as behavioral
      measures of impulsivity and risk-taking. METHODS: Outcome-related negativity
      (ORN/N2) and positivity (ORP/P3) derived from a single outcome gambling task were
      analyzed using a mixed model procedure. Current density was compared across
      groups and outcomes using standardized low resolution electromagnetic tomography
      (sLORETA). Behavioral scores were also compared across groups. Correlations of
      ERP factors with behavioral and impulsivity factors were also analyzed. RESULTS:
      Alcoholics showed significantly lower amplitude than controls during all outcome
      conditions for the ORP component and decreased amplitude during the loss
      conditions for the ORN component. Within conditions, gain produced higher
      amplitudes than loss conditions. Topographically, both groups had an anterior
      focus during loss conditions and posterior maxima during gain conditions,
      especially for the ORN component. Decreased ORP current density at cingulate
      gyrus and less negative ORN current density at sensory and motor areas
      characterized the alcoholics. Alcoholics had higher levels of impulsivity and
      risk-taking features than controls. CONCLUSIONS: Deficient outcome/reward
      processing and increased impulsivity and risk-taking observed in alcoholics may
      be at least partly due to reward deficiency and/or dysfunctional reward circuitry
      in the brain, suggesting that alcoholism can be considered as part of the cluster
      of the reward deficiency syndrome (RDS).

PMID- 20035956
TI  - Brassinosteroids control AtEXPA5 gene expression in Arabidopsis thaliana.
AB  - To elucidate the spatial and temporal roles of EXPANSIN A5 (AtEXPA5) in growth
      and development of Arabidopsis thaliana, phenotypic alterations in loss-of
      function mutants were observed. Seedlings of the null mutant, expA5-1, had
      shorter roots and hypocotyls than those of wild-type plants under both light and
      dark conditions. Compared to wild-type plants, the mutants had smaller rosette
      leaves. AtEXPA5 was dominantly expressed in aerial parts of A. thaliana,
      especially in the inflorescence stems and flowers. Expression of AtEXPA5 was
      enhanced by exogenously applied brassinosteroids. AtEXPA5 expression was reduced
      in a brassinosteroid-deficient mutant (det2) and a signaling mutant (bri1-301),
      while it was increased in bzr1-1D, a dominant mutant of a brassinosteroid
      transcription factor. A double mutant, bzr1-1DXexpA5-1, showed reduced growth
      compared to the bzr1-1D mutant. In addition, the brassinazole resistance of bzr1
      1D was impaired in the double mutant. These findings indicate that AtEXPA5 is a
      growth-regulating gene whose expression is controlled by brassinosteroid
      signaling downstream of BZR1 in A. thaliana.

PMID- 20035957
TI  - Aspects to be considered in extreme-temperature prevention plans in the light of
      new research.

PMID- 20035958
TI  - [Solitary fibrous tumor: imaging findings and review of the literature].
AB  - Solitary fibrous tumors of the liver are uncommon. First reported in the pleura,
      this tumor has also been reported in other locations both within and outside the
      thorax. It rarely affects the liver parenchyma. The clinical, radiological, and
      immunohistochemical findings characterize the lesion and distinguish it from
      other tumors with a similar appearance. We present the case of a solitary fibrous
      tumor in the liver; we place special emphasis on the findings at ultrasonography,
      computed tomography, and magnetic resonance imaging. Finally, we review the
      literature.

PMID- 20035959
TI  - [Varices in the round ligament].
AB  - Varices in the round ligament are very rare and have only been reported in
      pregnant women as an inguinal mass normally detected in the third trimester of
      gestation. B-mode and Doppler color ultrasonography are fundamental tools in the
      diagnosis, because they make it possible to reach a conclusive diagnosis and to
      rule out other clinically possible inguinal masses. Given that the treatment is
      conservative, it is essential for the radiologist to be familiar with this
      condition and its ultrasonographic characteristics to enable the correct
      diagnosis and avoid unnecessary surgical exploration.

PMID- 20035960
TI  - [Coronary artery calcium quantification with non-ECG-gated low-radiation dose CT
      of the chest].
AB  - OBJECTIVE: To evaluate the feasibility of quantifying coronary artery
      calcification in low-radiation dose chest CT (LDCT) studies performed in an early
      lung cancer detection program by comparing the results of this technique with
      those of dedicated retrospectively ECG-gated cardiac CT. MATERIAL AND METHODS:
      After obtaining informed consent, we evaluated the CT studies of 48 consecutive
      asymptomatic smokers (44 male, 4 female; mean age 59.7 years) included in an
      early lung cancer detection trial who underwent multislice LDCT (Volume Zoom,
      Siemens) of the chest and a retrospectively ECG-gated cardiac CT specifically
      dedicated to quantifying coronary artery calcification. LDCT examinations were
      reconstructed to reproduce cardiac CT parameters. Coronary calcium values were
      compared using the Wilcoxon signed-rank test. The concordance correlation
      coefficient (CCC) was calculated to determine the agreement between the two
      methods. RESULTS: Coronary calcium values ranged from 0 to 1,908.4 (median: 89.6;
      IQR: 3.2; 227.4) in LDCT exams and from 0 to 1,486.6 (median: 81.3; IQR: 2.5;
      316.4) in cardiac CT studies. No statistically significant difference was
      observed in the estimation of total coronary calcium score (p=0.28). The
      concordance between the two techniques was excellent (CCC > or = 0.81).
      CONCLUSION: The LDCT study performed in lung cancer early detection trials
      enables coronary artery calcification to be quantified with the same accuracy as
      the dedicated retrospectively ECG-gated cardiac CT examination.

PMID- 20035961
TI  - [The rabbit as an experimental model: technique for the induction of vascular
      lesions and incidents].
AB  - OBJECTIVE: To describe the process for inducing atherogenic lesions in rabbits,
      to show the damage to vessels caused by two different caliber balloon catheters,
      and to show the usefulness of ultrasonography in the quantification of vascular
      damage. MATERIAL AND METHODS: We used 36 rabbits. We studied the levels of
      triglycerides and cholesterol and examined the aorta and iliac arteries by
      ultrasonography. We performed arteriography and induced a vascular lesion by
      denuding the left iliac artery with a balloon catheter: group A 2.5mm diameter
      balloon catheter, group B 3mm diameter balloon catheter. After 8 weeks on a
      hyperlipidic diet, biochemical and ultrasonographic measurements were repeated.
      RESULTS: Cholesterol before the diet: 37.96 + or - 19.3mg/dL and after the diet:
      1761 + or - 296.91 mg/dL. The baseline ultrasonographic measurements of vessel
      diameter were: aorta 4.1 + or - 0.7 mm, right iliac artery 3 + or - 0.3mm, left
      iliac artery 3 + or - 0.4mm. After vascular damage and 8 weeks hyperlipidic diet,
      in group A the ultrasonographic measurements of vessel diameter were: aortic
      lumen 2.78 + or - 1.21 mm, right iliac artery 2.18 + or - 0.81 mm, and the left
      iliac artery 1.16 + or - 0.63 mm; in group B, the aortic lumen measured 3.07 + or
      - 1.06 mm, the right iliac artery 2.53 + or - 0.9 mm, and the left iliac artery
      1.39 + or - 1.1 mm. Four rabbits died; in the 32 remaining rabbits, morbidity was
      higher with a 3 mm balloon catheter. CONCLUSION: After denudation with a balloon
      catheter and a hyperlipidic diet, the rabbits developed arterial stenosis. The
      damage with a 2.5 mm diameter catheter reduces complications.

PMID- 20035962
TI  - Extrinsic afferents supplying the ovine duodenum and ileum.
AB  - The study aimed at establishing the distribution of primary sensory neurons by
      means of retrograde tracers Diamidino Yellow (DY) and Fast Blue (FB) injected
      into both the sheep duodenum and ileum, respectively. Many DY-labelled cells were
      found in both the distal vagal ganglia (DVG) and the spinal ganglia (SG) from T9
      L3; on the contrary, the majority of the FB-labelled cells were found in the SG.
      In the SG, a double immunofluorescence stain was used to reveal Nitric Oxide
      Synthase-Immunoreactivity (NOS-IR) in association with: substance P (SP),
      calcitonin gene-related peptide (CGRP), neurofilament 200kDa (NF) and isolectin
      B(4) (IB4). The labelled neurons, both DY and FB generally ranged in size from
      medium to large. The majority of the SG duodenal projections were NOS negative;
      the majority of the SG ileal afferent neurons expressed NOS-IR. Both DY and FB
      NOS-IR neurons often co-localized IB4, CGRP and SP, but rarely NF.

PMID- 20035963
TI  - Development and evaluation of an indirect enzyme-linked immunosorbent assay for
      the detection of antibodies against Campylobacter fetus in cattle.
AB  - Campylobacteriosis is a zoonosis that occurs worldwide. Infection with
      Campylobacter fetus (C. fetus) causes infertility and abortion in sheep and
      cattle. The current study focuses on the SapA gene of C. fetus that encodes
      surface array proteins and plays an important role in the virulence of C. fetus.
      The SapA-N (1398bp) and SapA-C (1422bp) fragments were amplified from the C.
      fetusSapA gene using polymerase chain reaction (PCR), and the corresponding
      recombinant proteins rSapA-N and rSapA-C were expressed in Escherichia. coli BL21
      cells. Results of Western blotting and enzyme-linked immunosorbent assay (ELISA)
      showed that the immunological activity of rSapA-N was higher than that of rSapA-C
      (P<0.05). Therefore, rSapA-N was selected to establish an indirect ELISA for
      detecting antibodies against C. fetus. The diagnostic criteria were as follows:
      S/P0.45: positive; S/P<0.4: negative; 0.45>S/P0.4: suspected. The specificity and
      sensitivity of our method were 94.3% and 88.6%, respectively. Moreover, no cross
      reactions were observed between rSapA-N and serum samples that were positive for
      other bovine bacterial pathogens diseases such as Mycobacterium avium subspecies
      paratuberculosis. One hundred and two serum samples from cows that had
      experienced abortion were tested. Four and 2 C. fetus-positive serum samples were
      found among the 70 bovine brucellosis-positive samples and the 32 infectious
      bovine rhinotracheitis (IBR)-positive samples, respectively. The findings suggest
      that the rSapA-N-based ELISA method has immense potential in future applications.

PMID- 20035964
TI  - Comparative efficacy of several disinfectants in suspension and carrier tests
      against Haemophilus parasuis serovars 1 and 5.
AB  - The comparative efficacy of 16 active compounds (including the most commonly used
      chemical groups) and 10 commercial formulations against Haemophilus parasuis
      serovars 1 and 5 was studied. These organisms were tested in suspension and
      carrier tests in the presence and absence of serum as representative of organic
      matter. Chloramine-T and half of the formulations from commercial sources (most
      of them including quaternary ammonium compounds) were effective in both in vitro
      tests, regardless of the presence or absence of organic load. All 26
      disinfectants except for an iodophor (0.1% available iodine) resulted in at least
      3-log(10) reduction in colony-forming units in suspension test, and most of them
      resulted in the maximal level of detection (>6-log(10) reduction). On the other
      hand, disinfectants were not as effective in carrier test as in suspension test,
      and the presence of serum considerably reduced the activities of most of the
      compounds tested, especially in carrier test. These results suggest the
      importance of selecting suitable disinfection for routine use on surfaces
      contaminated with H. parasuis, particularly when organic matter is present.
      Chloramine-T and formulations 2 and 7-10 are recommended for a complete
      inactivation of H. parasuis in swine herds.

PMID- 20035966
TI  - Bioregeneration of activated carbon and activated rice husk loaded with phenolic
      compounds: Kinetic modeling.
AB  - A kinetic model consisting of first-order desorption and biodegradation processes
      was developed to describe the bioregeneration of phenol- and p-nitrophenol-loaded
      powdered activated carbon (PAC) and pyrolyzed rice husk (PRH), respectively.
      Different dosages of PAC and PRH were loaded with phenol or p-nitrophenol by
      contacting with the respective phenolic compound at various concentrations. The
      kinetic model was used to fit the phenol or p-nitrophenol concentration data in
      the bulk solution during the bioregeneration process to determine the rate
      constants of desorption, k(d), and biodegradation, k. The results showed that the
      kinetic model fitted relatively well (R(2)>0.9) to the experimental data for the
      phenol- and p-nitrophenol-loaded PAC as well as p-nitrophenol-loaded PRH.
      Comparison of the values of k(d) and k shows that k is much greater than k(d).
      This indicates clearly that the desorption process is the rate-determining step
      in bioregeneration and k(d) can be used to characterize the rate of
      bioregeneration. The trend of the variation of the k(d) values with the dosages
      of PAC or PRH used suggests that higher rate of bioregeneration can be achieved
      under non-excess adsorbent dosage condition.

PMID- 20035965
TI  - Bisphenol A removal from wastewater using self-organized TIO(2) nanotubular array
      electrodes.
AB  - Photoelectrocatalytic oxidation of 0.1mM of Bisphenol A (BPA) leads to 100% of
      degradation monitored by liquid chromatography with diode array optical detection
      (limit 1microgL(-1)) and 100% TOC removal. Optimum performance was obtained using
      TiO(2) nanotubular array (NTA) electrodes, grown by anodization of Ti foil in
      0.25wt.% NH(4)F and a mixture of glycerol and water (ratio 90:10vol.%) using an
      applied voltage of 20V for 50h. The effects of supporting electrolyte, pH,
      applied bias potential and BPA concentration were evaluated as to their effect on
      the BPA degradation kinetics and the best condition was found to be 0.1M
      Na(2)SO(4) at pH 6 as supporting electrolyte and applied bias potential of +1.5V
      vs. Ag/AgCl under UV irradiation. Our findings indicate that TiO(2) NTAs prepared
      by anodization are versatile and efficient photocatalysts for the degradation of
      endocrine disruptors.

PMID- 20035967
TI  - A bivariate approach to the widening of the frontal lobes in the genus Homo.
AB  - Within the genus Homo, the most encephalized taxa (Neandertals and modern humans)
      show relatively wider frontal lobes than either Homo erectus or
      australopithecines. The present analysis considers whether these changes are
      associated with a single size-based or allometric pattern (positive allometry of
      the width of the anterior endocranial fossa) or with a more specific and non
      allometric pattern. The relationship between hemispheric length, maximum
      endocranial width, and frontal width at Broca's area was investigated in extant
      and extinct humans. Our results do not support positive allometry for the frontal
      lobe's width in relation to the main endocranial diameters within modern humans
      (Homo sapiens). Also, the correlation between frontal width and hemispheric
      length is lower than the correlation between frontal width and parieto-temporal
      width. When compared with the australopithecines, the genus Homo could have
      experienced a non-allometric widening of the brain at the temporo-parietal areas,
      which is most evident in Neandertals. Modern humans and Neandertals also display
      a non-allometric widening of the anterior endocranial fossa at the Broca's cap
      when compared with early hominids, again more prominent in the latter group.
      Taking into account the contrast between the intra-specific patterns and the
      between-species differences, the relative widening of the anterior fossa can be
      interpreted as a definite evolutionary character instead of a passive consequence
      of brain size increase. This expansion is most likely associated with
      correspondent increments of the underlying neural mass, or at least with a
      geometrical reallocation of the frontal cortical volumes. Although different
      structural changes of the cranial architecture can be related to such variations,
      the widening of the frontal areas is nonetheless particularly interesting when
      some neural functions (like language or working memory, decision processing,
      etc.) and related fronto-parietal cortico-cortical connections are taken into
      account.

PMID- 20035968
TI  - Alteration of arsenopyrite in soils under different vegetation covers.
AB  - The weathering of arsenopyrite (FeAsS) has been monitored in soils using an in
      situ experimental approach. Arsenopyrite in nylon experimental bags was placed in
      individual horizons in soils in spruce (litter, horizons A, B, and C), beech
      (litter, horizons A, B, and C) and unforested (horizons A, B, and C) areas and
      left in contact with the soil for a period of 1 year. The individual areas on the
      ridge of the Krusne hory Mts., Czech Republic, had the same lithology, climatic
      and environmental conditions. Scorodite (FeAsO(4).2H(2)O) was identified as a
      principal secondary mineral of arsenic (As) formed directly on the surface of the
      arsenopyrite. Scorodite was formed in all the areas in all soil horizons. The
      amount of scorodite formed decreased in the series beech, spruce and unforested
      areas. In forested areas, there was a larger amount of scorodite on arsenopyrites
      exposed in organic horizons (litter, A horizon). The greater rate of arsenopyrite
      alteration in organic horizons in the beech stand compared to spruce stand is
      probably a result of faster mineralization of organic material with resulting
      production of nitrate and better seepage conditions of soil in this area.
      Speciation of As determined using the sequential extraction technique
      demonstrated that As was bonded in the soils primarily in the residual fractions
      prior to the experiment. The As content in the mobile fractions increased in the
      organic horizon in the forested areas after the experiments.

PMID- 20035969
TI  - Modeled and monitored variation in space and time of PCB-153 concentrations in
      air, sediment, soil and aquatic biota on a European scale.
AB  - We evaluated various modeling options for estimating concentrations of PCB-153 in
      the environment and in biota across Europe, using a nested multimedia fate model
      coupled with a bioaccumulation model. The most detailed model set up estimates
      concentrations in air, soil, fresh water sediment and fresh water biota with
      spatially explicit environmental characteristics and spatially explicit emissions
      to air and water in the period 1930-2005. Model performance was evaluated with
      the root mean square error (RMSE(log)), based on the difference between estimated
      and measured concentrations. The RMSE(log) was 5.4 for air, 5.6-6.3 for sediment
      and biota, and 5.5 for soil in the most detailed model scenario. Generally, model
      estimations tended to underestimate observed values for all compartments, except
      air. The decline in observed concentrations was also slightly underestimated by
      the model for the period where measurements were available (1989-2002). Applying
      a generic model setup with averaged emissions and averaged environmental
      characteristics, the RMSE(log) increased to 21 for air and 49 for sediment. For
      soil the RMSE(log) decreased to 3.5. We found that including spatial variation in
      emissions was most relevant for all compartments, except soil, while including
      spatial variation in environmental characteristics was less influential. For
      improving predictions of concentrations in sediment and aquatic biota, including
      emissions to water was found to be relevant as well.

PMID- 20035970
TI  - Ecological risk assessment of zinc from stormwater runoff to an aquatic
      ecosystem.
AB  - Zinc (Zn) risks from stormwater runoff to an aquatic ecosystem were studied.
      Monitoring data on waterborne, porewater, and sediment Zn concentrations
      collected at 20 stations throughout a stormwater collection/detention facility
      consisting of forested wetlands, a retention pond and first order stream were
      used to conduct the assessment. Bioavailability in the water column was estimated
      using biotic ligand models for invertebrates and fish while bioavailability in
      the sediment was assessed using acid volatile sulfide-simultaneously extracted
      metal (AVS-SEM). The screening level assessment indicated no significant risks
      were posed to benthic organisms from Zn concentrations in sediments and pore
      water. As would be expected for stormwater, Zn concentrations were temporally
      quite variable within a storm event, varying by factors of 2 to 4. Overall,
      probabilistic assessment indicated low (5-10% of species affected) to negligible
      risks in the system, especially at the discharge to the first order stream.
      Moderate to high risks (10-50% of species affected) were identified at sampling
      locations most upgradient in the collection system. The largest uncertainty with
      the assessment is associated with how best to estimate chronic exposure/risks
      from time-varying exposure concentrations. Further research on pulse exposure
      metal toxicity is clearly needed to assess stormwater impacts on the environment.

PMID- 20035971
TI  - Parameter uncertainty analysis of non-point source pollution from different land
      use types.
AB  - Land use type is one of the most important factors that affect the uncertainty in
      non-point source (NPS) pollution simulation. In this study, seventeen sensitive
      parameters were screened from the Soil and Water Assessment Tool (SWAT) model for
      parameter uncertainty analysis for different land use types in the Daning River
      Watershed of the Three Gorges Reservoir area, China. First-Order Error Analysis
      (FOEA) method was adopted to analyze the effect of parameter uncertainty on model
      outputs under three types of land use, namely, plantation, forest and grassland.
      The model outputs selected in this study consisted of runoff, sediment yield,
      organic nitrogen (N), and total phosphorus (TP). The results indicated that the
      uncertainty conferred by the parameters differed among the three land use types.
      In forest and grassland, the parameter uncertainty in NPS pollution was primarily
      associated with runoff processes, but in plantation, the main uncertain
      parameters were related to runoff process and soil properties. Taken together,
      the study suggested that adjusting the structure of land use and controlling
      fertilizer use are helpful methods to control the NPS pollution in the Daning
      River Watershed.

PMID- 20035972
TI  - Contamination of surface and potable water in South Asia by Salmonellae: culture
      independent quantification with molecular beacon real-time PCR.
AB  - Low numbers (15-100CFU) of Salmonella in food or water may pose a public health
      risk. The management of infections caused by Salmonella spp. during outbreaks or
      forecasting of contamination of aquatic resources largely depends on rapid,
      sensitive and accurate diagnostic in few hours. In this study, a real-time PCR
      assay in Molecular-Beacon format was developed and culture-independent
      quantitative enumeration of Salmonella spp. in surface and potable water is being
      reported for the first time from northern part of India. Molecular Beacon was
      designed in highly conserved region of invA gene (present in wide range of
      Salmonella serotypes including all subspecies) encoding an essential component of
      the invasion associated specialized type O protein secretion apparatus for
      detection of Salmonella spp. in water. The assay could detect directly 10 and 1
      genomic equivalent of Salmonella typhimurium ATCC 14028 per PCR with detection
      probability of 100 and 20%, respectively. Further, the assay could detect
      10CFU/PCR or more of reference strain (S. typhimurium ATCC 14028) without any
      enrichment in the presence of 10(8)CFUml(-1) of non-pathogenic E. coli (E. coli
      DH5alpha) with 100% detection probability. The assay could enumerate Salmonella
      spp. in surface (n=40) and potable waters (n=10) directly (without enrichment).
      Results indicate that northern India is at high risk of developing Salmonella
      borne infections. Further, real-time PCR assay in Molecular Beacon format can be
      used for identification of critical contamination points in natural water
      resources and potable water distribution systems, necessary to implement
      vaccination plan timely for prevention of waterborne outbreaks caused by
      Salmonella spp.

PMID- 20035973
TI  - Low-molecular-weight heparin inhibition in classical complement activation
      pathway during pregnancy.
AB  - INTRODUCTION: Low-molecular-weight heparin is used clinically for the prevention
      of pregnancy complications associated with prothrombotic disorders, particularly
      anti-phospholipid syndrome. Nevertheless, recent studies have suggested that
      heparin may exert direct effects on the placental trophoblast, independently of
      its anticoagulant activity. In addition, heparin prevents complement activation
      in vivo and protects mice from pregnancy complications. MATERIALS AND METHODS:
      The inhibition of the classical complement activation pathway by heparin was
      analyzed by means of in vitro assays and in pregnant women receiving prophylaxis
      with therapeutic doses (40 mg/day) of subcutaneous low molecular weight heparin
      by haemolysis of antibody-sensitized sheep erythrocytes (CH(50) assay). RESULTS:
      The specific interaction between low-molecular-weight heparin and the C1q subunit
      of the C1 complex of the complement cascade allowed the isolation of a small
      subpopulation of heparin ( 8.03+/-1.20 microg %), with an anti-activated factor X
      activity more than four times greater than the starting material. This
      subpopulation could be responsible for the in vitro inhibition of the classical
      complement activation pathway evaluated by the total haemolysis of antibody
      sensitized sheep erythrocytes. About 60 microg/ml of low molecular weight heparin
      was needed to achieve 50% of haemolysis. The detection of the classical
      complement pathway inhibition in pregnant women treated with heparin required a
      first activation with aggregated human IgG. CONCLUSIONS: We concluded that the
      interaction between low-molecular-weight heparin and C1q could be relevant not
      only in the complement-dependent, but also in the complement-independent
      inflammation mechanisms responsible for the prevention of pregnancy loss.

PMID- 20035974
TI  - 2,8-dihydroxyadenine nephrolithiasis induces developmental stage-specific
      alterations in gene expression in mouse kidney.
AB  - OBJECTIVES: To identify factors that may be crucial for the initiation and
      progression of stone-induced injury in the developing mouse kidney by a
      prospective observational study using microarray analysis. Kidney stone diseases
      are common in premature infants, but the underlying molecular and cellular
      mechanisms are not fully defined. METHODS: Mice with adenine
      phosphoribosyltransferase deficiency develop 2,8-dihydroxyadenine (DHA)
      nephrolithiasis. The gene expression changes between Aprt(-/-) and Aprt(+/+)
      kidneys from newborn and adult mice were compared using Affymetrix gene chips.
      Targets of interest were further analyzed by quantitative real-time polymerase
      chain reaction and immunohistochemistry. RESULTS: We identified a set of genes
      that were differentially expressed in the developing kidney in response to DHA
      induced injury. In 1-week-old Aprt(-/-) mice, the expression of Sprr2f and Clu
      was highly augmented and that of Egf was significantly decreased. We also
      observed that maturation-related gene expression changes were delayed in
      developing Aprt(-/-) kidneys, and immature Aprt(-/-) kidneys contained large
      numbers of intercalated cells that were blocked from terminal differentiation.
      CONCLUSIONS: This study presents a comprehensive picture of the transcriptional
      changes induced by DHA stone injury in the developing mouse kidney. Our findings
      help explain growth impairment in kidneys subject to injury during the early
      stages of development.

PMID- 20035975
TI  - Identification of a microRNA panel for clear-cell kidney cancer.
AB  - OBJECTIVES: To identify a robust panel of microRNA signatures that can classify
      tumor from normal kidney using microRNA expression levels. Mounting evidence
      suggests that microRNAs are key players in essential cellular processes and that
      their expression pattern can serve as diagnostic biomarkers for cancerous
      tissues. METHODS: We selected 28 clear-cell type human renal cell carcinoma
      (ccRCC), samples from patient-matched specimens to perform high-throughput,
      quantitative real-time polymerase chain reaction analysis of microRNA expression
      levels. The data were subjected to rigorous statistical analyses and hierarchical
      clustering to produce a discrete set of microRNAs that can robustly distinguish
      ccRCC from their patient-matched normal kidney tissue samples with high
      confidence. RESULTS: Thirty-five microRNAs were found that can robustly
      distinguish ccRCC from their patient-matched normal kidney tissue samples with
      high confidence. Among this set of 35 signature microRNAs, 26 were found to be
      consistently downregulated and 9 consistently upregulated in ccRCC relative to
      normal kidney samples. Two microRNAs, namely, MiR-155 and miR-21, commonly found
      to be upregulated in other cancers, and miR-210, induced by hypoxia, were also
      identified as overexpressed in ccRCC in our study. MicroRNAs identified as
      downregulated in our study can be correlated to common chromosome deletions in
      ccRCC. CONCLUSIONS: Our analysis is a comprehensive, statistically relevant study
      that identifies the microRNAs dysregulated in ccRCC, which can serve as the basis
      of molecular markers for diagnosis.

PMID- 20035976
TI  - Osteoblast-specific factor 2 expression in prostate cancer-associated stroma:
      identification through microarray technology.
AB  - OBJECTIVES: To better understand the gene expression patterns in tumor-associated
      stroma, laser-capture-microdissections from clinical specimens were analyzed by
      genome-wide-expression microarray technology. The epithelial-stromal interaction
      plays a critical role in prostate development, reactive changes, and
      tumorigenesis. Diverse microarray technologies have been used to characterize the
      molecular changes in prostate cancer. Even though these gene expression studies
      are compromised by the heterogeneity of the tumor, as well as by the difficulty
      associated with collecting appropriate counterparts to represent normal prostate
      cells, the gene array data from tumors have shown promising results. Currently,
      little is known about the tumor-associated stromal gene expression profile in
      prostate cancer. METHODS: Matching benign and malignant epithelial cell-related
      stroma cells were subjected to microarray platforms. RESULTS: The prostatatic
      stroma expressed several osteogenic molecules. In particular, one of the genes,
      OSF2, was upregulated in tumor-associated stroma compared with benign epithelial
      cell associated stroma, which was further validated by immunohistochemical
      examination. CONCLUSIONS: These data show that the combination of laser capture
      dissection with computational enhancement of epithelial and stromal microarray
      data is a useful tool to assess gene expression changes in prostate cancer
      stroma.

PMID- 20035977
TI  - Economic costs of overactive bladder in the United States.
AB  - OBJECTIVES: To calculate, from a societal perspective, current direct (medical
      and nonmedical) and indirect costs of overactive bladder (OAB) in the United
      States and project them to future years. Existing cost assessments of OAB in the
      United States are incomplete and outdated. METHODS: A prevalence-based model was
      developed incorporating age- and sex-specific OAB prevalence rates, usage data,
      and productivity data. On the basis of the information gathered from the recent 5
      years of the medical literature, practice guidelines, Medicare and managed care
      fee schedules, and expert panel input, the annual per capita and total US costs
      were calculated for 2007. US census population forecasts were used to project the
      costs of OAB to 2015 and 2020. RESULTS: In 2007, average annual per capita costs
      of OAB were $1925 ($1433 in direct medical, $66 in direct nonmedical, and $426 in
      indirect costs). Applying these costs to the 34 million people in the United
      States with OAB results in total national costs of $65.9 billion (billion = 1000
      million), ($49.1 billion direct medical, $2.3 billion direct nonmedical, and
      $14.6 billion indirect). Average annual per capita costs in 2015 and 2020 would
      be $1944 and $1969 and total national costs would be $76.2 billion and $82.6
      billion, respectively. CONCLUSIONS: These data suggest that the economic burden
      of OAB is about 5-fold higher than older, noncomprehensive estimates. These costs
      are higher than previously published data for the United States and Europe
      because this analysis relies on more current data, real world age- and sex
      specific treatment patterns and costs, and includes a more complete set of cost
      components.

PMID- 20035978
TI  - Preliminary results of prostate vaporization in the treatment of benign prostatic
      hyperplasia by using a 200-W high-intensity diode laser.
AB  - OBJECTIVES: To evaluate the efficacy and safety of a 200-W high-intensity diode
      laser in the treatment of benign prostatic hyperplasia. METHODS: The prostate was
      vaporized by using a side-firing laser fiber (diode laser: power, 150-200 W;
      wavelength, 980 nm; Limmer, Germany). The following parameters were assessed at
      baseline, and after a follow-up period of 1- and 6 months: International Prostate
      Symptom Score, maximum uroflow rate, postvoid residual urine volume, and quality
      of life score. Prostate volume and prostate-specific antigen levels were assessed
      at baseline and 6 months postoperatively. RESULTS: This study included 55
      patients diagnosed with lower urinary tract symptoms secondary to BPH, who were
      treated between December 2007 and July 2008. The recatheterization rate was
      10.9%. None of these patients required a blood transfusion or had transurethral
      resection syndrome. Statistically significant improvements (P < .001) were
      observed in the values of International Prostate Symptom Score, Q(max), postvoid
      residual urine volume, and quality of life score at 1- and 6 months of follow-up
      as compared with the respective baseline values. Transient urge incontinence was
      noted in 8 patients (8/55, 14.5%).Sloughing of necrotic tissues was observed on
      cystoscopy in 8 patients within several weeks or months after the operation. The
      retreatment rate (secondary transurethral resection of the prostate) was 7.3%.
      CONCLUSIONS: From our preliminary data, it was evident that diode laser
      prostatectomy can achieve excellent hemostasis, and provide immediate relief from
      obstructive voiding symptoms. However, the postoperative irritative symptoms and
      sloughing of necrotic tissues remained to be an important issue that needed to be
      resolved.

PMID- 20035979
TI  - Pelvic reduction during pyeloplasty for antenatal hydronephrosis: does it affect
      outcome in ultrasound and nuclear scan postoperatively?
AB  - OBJECTIVE: To compare ultrasound (US) scan and nuclear renography findings in
      patients who underwent pyeloplasty with and without pelvic reduction in a
      randomized prospective study. METHODS: A total of 42 patients, all prenatally
      diagnosed with unilateral hydronephrosis, were included. Hydronephrosis was
      confirmed postnatally. Twenty patients were randomly selected to undergo
      pyeloplasty with pelvic reduction and 22 underwent pelvis-sparing pyeloplasty.
      Patients were evaluated with mercaptoacetyltriglycine-3 scans on the sixth month
      and US scans on the first, third, and sixth months, postoperatively. Mean follow
      up was 37 +/- 5.6 weeks. Statistical analyses were performed using chi-square
      test and significance was set as P <.05. Power analyses were performed by the
      NCSS-PASS program. Power value of 0.84 was calculated for a sample size of 42.
      RESULTS: The anteroposterior pelvic diameter decreased significantly in the
      pelvic reduction group compared with pelvis-sparing group in the first- and third
      month US scans. However, the difference was not significant in the sixth month.
      The improvements in the US findings for the pelvis-sparing group match with those
      of the pelvic reduction group later in the postoperative period. Pelvic reduction
      significantly improved the renal washout time (T(1/2)) in
      mercaptoacetyltriglycine-3 renography when compared with pyeloplasty group
      without reduction at postoperative sixth month. Differential renal function was
      found to be unaffected from pelvic reduction. CONCLUSIONS: Resolution of
      anteroposterior diameter in US scan is more prominent in the pelvic reduction
      group at earlier stages of the postoperative period. Although T(1/2) decreases
      more prominently in the pelvic reduction group, the utility of this procedure is
      still indecisive. This feature can reveal possible surgical failures earlier and
      strengthen the values of US and renography postoperatively.

PMID- 20035981
TI  - Identification of spermatozoa in archived testicular cancer specimens:
      implications for bench side sperm retrieval at orchiectomy.
AB  - OBJECTIVES: To evaluate the patterns of spermatogenesis in the normal testicular
      parenchyma of primary testicular cancers and estimate the feasibility of sperm
      retrieval at the time of radical orchiectomy. METHODS: We reviewed the archived
      histologic sections of 39 consecutive patients who had undergone radical
      orchiectomy for primary testicular cancer at 3 university-affiliated hospitals.
      We examined all areas of normal (noncancerous) testicular parenchyma to evaluate
      the level of spermatogenesis and presence of mature spermatozoa in these
      sections. A minimum of 100 seminiferous tubules were scored per case. We also
      evaluated the epididymal tubules for the presence of mature spermatozoa. A review
      of the clinical chart was performed to evaluate the relationship between clinical
      data and histologic findings. RESULTS: In nearly 40% of the cases evaluated
      (15/38), the predominant histologic pattern was full spermatogenesis. Mature
      spermatozoa were identified in nearly 80% (30/38) of the testicular histologic
      sections and in 50% (14/28) of the evaluable epididymal sections. Clinical stage
      (presence of extranodal disease) and tumor marker levels were related to the
      probability of identifying mature spermatozoa in the testis. CONCLUSIONS: The
      data suggest that sperm retrieval at the time of radical orchiectomy is a
      feasible fertility option, with a 40% probability of recovering spermatozoa by
      random biopsy of the noncancerous testicular parenchyma and an 80% probability of
      recovering spermatozoa with a more extensive dissection. In 50% men, spermatozoa
      may be recovered by epididymal aspiration alone.

PMID- 20035980
TI  - Treatment of pediatric vesicoureteral reflux using endoscopic injection of
      hyaluronic acid/dextranomer gel: intermediate-term experience by a single
      surgeon.
AB  - OBJECTIVES: Endoscopic injection of non-animal-stabilized hyaluronic
      acid/dextranomer gel is an increasingly recognized treatment option for
      vesicoureteral reflux. The procedure is minor compared with open surgery and,
      when successful, avoids the need for long-term antibiotic prophylaxis. We present
      data from 3 years of using non-animal-stabilized hyaluronic acid/dextranomer gel
      to treat children with vesicoureteral reflux. METHODS: Pediatric patients aged 16
      years with uncomplicated primary vesicoureteral reflux were recruited for
      endoscopic treatment with non-animal-stabilized hyaluronic acid/dextranomer gel.
      A follow-up voiding cystourethrogram was scheduled at 2 weeks after treatment,
      and vesicoureteral reflux resolution was defined as grade 0. Repeat non-animal
      stabilized hyaluronic acid/dextranomer gel treatment was offered to patients with
      persistent vesicoureteral reflux. RESULTS: Of 178 patients treated, 12 were lost
      to follow-up or yet to undergo post-treatment voiding cystourethrogram. The 166
      remaining patients (efficacy population) had a mean age of 4.21 years (range: 0
      16), and the median reflux grade was 3 (range: 1-5). Vesicoureteral reflux was
      resolved in 81.9% of patients and 86.4% of ureters after initial endoscopic
      treatment with non-animal-stabilized hyaluronic acid/dextranomer gel. The overall
      reflux resolution rate for patients increased to 89.6% after a second treatment
      in 19 patients, and 90.2% after a third treatment in 1 patient. No adverse events
      were reported. Five patients underwent open ureteral reimplantation after failed
      endoscopic injections. CONCLUSIONS: Endoscopic treatment with non-animal
      stabilized hyaluronic acid/dextranomer gel is effective in a high proportion of
      children with vesicoureteral reflux and, in our opinion, should be considered as
      a first-line treatment option.

PMID- 20035982
TI  - Prostate-specific antigen-based risk-adapted discontinuation of prostate cancer
      screening in elderly African American and Caucasian American men.
AB  - OBJECTIVES: To evaluate the relationship between initial prostate-specific
      antigen (PSA) and prostate cancer (PCa) risk in elderly African American (AA) and
      Caucasian American (CA) men. METHODS: A total of 408 AA and 1720 CA men whose
      initial PSA measurement was performed between 75 and 80 years of age were
      retrieved from Duke Prostate Center database. Patients were stratified by race
      and initial PSA value. The relative risk (RR) of PCa detection was estimated. The
      rates of high risk PCa, and death from PCa stratified by initial PSA groups were
      compared using the chi-square test. RESULTS: The age-adjusted RR of PCa detection
      in CA men with PSA 3.0-5.9 ng/mL was 1.9-fold higher when compared with that of
      men with PSA 0.0-2.9 ng/mL (P < .001), but it did not change significantly in AA
      men (P = .270). PSA 6.0-9.9 ng/mL was associated with age-adjusted RR of PCa 9.3
      fold in AA men and 4.1-fold in CA men (both P values < .001). A low rate of high
      risk PCa and death from PCa was indicated with PSA < 6.0 ng/mL and < 3.0 ng/mL
      and follow-up of a maximum of 19.2 years and 17.6 years, respectively, in AA and
      CA men. CONCLUSIONS: AA men with initial PSA < 6.0 ng/mL and CA men with initial
      PSA < 3.0 ng/mL between 75 and 80 years of age are unlikely to be diagnosed with
      high risk PCa or death from PCa. It may be safe to discontinue PSA screening in
      these men.

PMID- 20035983
TI  - Reduction in the risk of prostate cancer: future directions after the Prostate
      Cancer Prevention Trial.
AB  - The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the
      potential health benefits and cost of reducing prostate cancer risk-
      specifically, the potential role of 5alpha-reductase inhibitors. However, the
      PCPT raised several unanswered questions, including the cause and significance of
      the increased incidence of high-grade tumors associated with finasteride. In the
      present study, we review the PCPT findings and unanswered questions, next steps
      in this field, and ongoing prostate cancer prevention trials addressing these
      unanswered questions. Particular emphasis is placed on the design of the second
      large-scale trial of a 5alpha-reductase inhibitor, the REduction by DUtasteride
      of prostate Cancer Events (REDUCE) trial.

PMID- 20035984
TI  - Repeated injections of botulinum toxin-A for idiopathic detrusor overactivity.
AB  - OBJECTIVES: To report the efficacy and safety of repeated injections of botulinum
      toxin-A (BTX-A) in treating idiopathic detrusor overactivity refractory to
      anticholinergics. Furthermore, we describe whether dose alteration in patients
      with poor responses or voiding dysfunction after initial treatment can improve
      outcomes. METHODS: A cohort of 34 patients who participated in a clinical trial
      was followed up and their progress reported. Twenty from this group had >1 BTX-A
      injection. Each patient received 200 U BTX-A initially, with subsequent
      injections between 100 and 300 U, administered by a trigone-sparing flexible
      cystoscopic technique. Efficacy was measured using voiding diaries and quality of
      life (QoL) assessed with Incontinence Impact Questionnaire-7 and Urogenital
      Distress Inventory-6 questionnaires. Urodynamic data were obtained for injections
      1-3. All measurements were performed before and 3 months after injections.
      RESULTS: Twenty patients received a repeat injection and of these 9 subsequently
      received a third and fourth injection. Significant improvements in overactive
      bladder syndrome symptoms and QoL were observed after each injection as compared
      with baseline. Maximum cystometric capacity and bladder compliance increased with
      decrease in the maximum detrusor pressure during filling cystometry. When
      comparing overactive bladder symptoms, QoL, and urodynamic parameters 3 months
      after the first and last injections, no significant differences were found. Nine
      patients had their BTX-A dose altered, with better outcomes in 5. The commonest
      reported problems were difficulty in emptying the bladder and urinary tract
      infection. CONCLUSIONS: BTX-A appears to be effective and safe after repeated
      administration in patients with idiopathic detrusor overactivity. Certain
      patients will benefit from dose optimization to improve efficacy or prevent
      voiding dysfunction.

PMID- 20035985
TI  - Transperitoneal laparoscopic radical nephrectomy for patients with dialysis
      dependent end-stage renal disease: an analysis and comparison of perioperative
      outcome.
AB  - OBJECTIVES: To evaluate LRN as treatment for high risk patients. Laparoscopic
      radical nephrectomy (LRN) is performed for renal tumors not amenable to nephron
      sparing treatments. Indications are increasing to include higher risk patients
      including those with end-stage renal disease (ESRD) necessitating dialysis.
      METHODS: We performed a retrospective analysis of a patient cohort with clinical
      stage T1 renal tumors undergoing transperitoneal LRN. Parameters examined
      included patient demographics, medical comorbidities, tumor characteristics,
      operative outcomes, and complications. RESULTS: One hundred eighty-nine patients
      underwent 195 LRN. Sixteen patients (8.5%) had preexistent ESRD requiring
      dialysis. A higher American Society of Anesthiologists score (P<.05), higher age
      adjusted Charlson comorbidity index (P=.003), higher incidence of previous
      abdominal surgery (P=.012), and higher incidence of hypertension (P=.025) were
      found for the ESRD group. Mean blood loss was 153.0 and 132.0 mL (P=.71) in the
      ESRD patients and non-ESRD patients, respectively. A longer stay (P=.02) was
      noted for ESRD patients. Mean tumor size in the ESRD patients and non-ESRD
      patients was 2.6 and 4.2 cm (P<.05), respectively. Renal cell carcinoma was the
      most common pathology in 14 of 20 (70.0%) ESRD patient renal units and 167 of 175
      (95.4%) non-ESRD patient renal units (P=.001). Intraoperative and postoperative
      complication rates were 6.3% and 31.3% respectively for ESRD patients (P=.05),
      and 8.7% and 21.4% respectively for non-ESRD patients (P=.35). Most postoperative
      complications were minor. CONCLUSIONS: LRN, for the treatment of renal tumors in
      ESRD patients requiring dialysis, is feasible and safe with acceptable
      intraoperative and postoperative complication rates. Patients with ESRD may
      require longer hospital stay after LRN.

PMID- 20035986
TI  - Median 5 year follow-up of 125iodine brachytherapy as monotherapy in men
      aged<or=55 years with favorable prostate cancer.
AB  - OBJECTIVES: To report the genitourinary (GU) and gastrointestinal (GI) toxicity
      rates, erectile function preservation, and biochemical outcome (bNED) in men
      aged<or=55 years treated with 125iodine (125I) brachytherapy (BT). METHODS:
      Between May 1999 and November 2005, 96 men with clinical stage T1-T2 prostate
      cancer received 125I prostate BT without androgen deprivation or supplemental
      external radiotherapy. Median age was 53 years (range 45-55). Minimum follow-up
      was 30 months and median 63 months (range: 30-108). Biochemical failure was
      defined as "nadir+2." GI and GU toxicity are reported using common terminology
      criteria for adverse events (CTCAE) v3. RESULTS: Only 1 patient experienced a
      biochemical failure; the actuarial 7-year bNED rate is 98.9%. Median nadir is
      0.05 ng/mL, reached at 48 months of follow-up. Median 5- and 7-year prostate
      specific antigen were 0.09 and 0.06 ng/mL, respectively. Grade 2 acute and late
      GU toxicity rates (urinary frequency, urgency, and/or dysuria) were 9.8% and
      10.6%, respectively. Grade 3 GU toxicity (urethral stricture) was observed in 3
      men and was corrected with urethral dilatation or transurethral resection. Two
      (2.2%) patients developed grade 2 GI toxicity (proctitis). Erectile function was
      preserved in 85 of 91 men with prior good function (93.4%); 41 (45%) used
      phosphodiesterase-5 inhibitors. CONCLUSIONS: Men aged<or=55 years treated with
      125I prostate BT without androgen deprivation or supplemental external beam
      radiotherapy experienced excellent bNED rates with low toxicity. Men in this age
      group should be offered low dose rate prostate BT as an option to consider.

PMID- 20035987
TI  - Effect of the association of IGF-I, IGF-II, bFGF, TGF-beta1, GM-CSF, and LIF on
      the development of bovine embryos produced in vitro.
AB  - This study examined the influence of the following growth factors and cytokines
      on early embryonic development: insulin-like growth factors I and II (IGF-I, IGF
      II), basic fibroblast growth factor (bFGF), transforming growth factor (TGF
      beta), granulocyte-macrophage colony-stimulating factor (GM-CSF), and leukemia
      inhibitory factor (LIF). Synthetic oviduct fluid (SOF) was used as the culture
      medium. We studied the development of bovine embryos produced in vitro and
      cultured until Day 9 after fertilization. TGF-beta1, bFGF, GM-CSF, and LIF used
      on their own significantly improved the yield of hatched blastocysts. IGF-I,
      bFGF, TGF-beta1, GM-CSF, and LIF significantly accelerated embryonic development,
      especially the change from the expanded blastocyst to hatched blastocyst stages.
      Use of a combination of these growth factors and cytokines (GF-CYK) in SOF medium
      produced higher percentages of blastocysts and hatched blastocysts than did use
      of SOF alone (45% and 22% vs. 24% and 12%; P<0.05) on Day 8 after in vitro
      fertilization and similar results to use of SOF+10% fetal calf serum (38% and
      16%, at the same stages, respectively). The averages of total cells, inner cell
      mass cells, and trophectoderm cells of exclusively in vitro Day-8 blastocysts for
      pooled GF-CYK treatments were higher than those for SOF and similar to those for
      fetal calf serum. The presence of these growth factors and cytokines in the
      embryo culture medium therefore has a combined stimulatory action on embryonic
      development; in particular through an increase in hatching rate and in the number
      of cells of both the inner cell mass and trophoblast. These results are the first
      to demonstrate that use of a combination of recombinant growth factors and
      cytokine, as IGF-I, IGF-II, bFGF, TGF-beta1, LIF, and GM-CSF, produces similar
      results to 10% fetal calf serum for the development of in vitro-produced bovine
      embryos. This entirely synthetic method of embryo culture has undeniable
      advantages for the biosecurity of embryo transfer.

PMID- 20035988
TI  - The association of normative perceptions with adolescent smoking intentions.
AB  - The social norms approach suggests that tobacco use among a referent population
      will reduce provided they are presented with accurate information about the
      perceived norms of that behaviour. This study investigated adolescents' perceived
      tobacco-related norms on future smoking intentions, using a sample of 11-16 year
      olds (n = 804) from wave two of the Youth Tobacco Policy Survey. Structural
      equation modelling was used to analyse, simultaneously, the hypothesized
      normative model on future smoking intentions among both adolescent smokers and
      never smokers. While among adolescent smokers perceived prevalence, perceptions
      of the tobacco industry and risk from smoking were associated with future smoking
      intentions, among never smokers only perceived sibling approval was associated
      with future smoking intentions. The research highlights the need for more
      comprehensive anti-tobacco related campaigns that incorporate messages and
      stimuli relevant to behaviour reflecting these normative types.

PMID- 20035989
TI  - Prevention is better than cure.

PMID- 20035990
TI  - Convection-driven generation of long-range material gradients.
AB  - Natural materials exhibit anisotropy with variations in soluble factors, cell
      distribution, and matrix properties. The ability to recreate the heterogeneity of
      the natural materials is a major challenge for investigating cell-material
      interactions and for developing biomimetic materials. Here we present a generic
      fluidic approach using convection and alternating flow to rapidly generate multi
      centimeter gradients of biomolecules, polymers, beads and cells and cross
      gradients of two species in a microchannel. Accompanying theoretical estimates
      and simulations of gradient growth provide design criteria over a range of
      material properties. A poly(ethylene-glycol) hydrogel gradient, a porous collagen
      gradient and a composite material with a hyaluronic acid/gelatin cross-gradient
      were generated with continuous variations in material properties and in their
      ability to regulate cellular response. This simple yet generic fluidic platform
      should prove useful for creating anisotropic biomimetic materials and high
      throughput platforms for investigating cell-microenvironment interactions.

PMID- 20035991
TI  - The ability of surface characteristics of materials to trigger leukocyte tissue
      factor expression.
AB  - Biomaterial-induced thrombosis is usually attributed to blood coagulation
      initiated by contact phase and platelet-related reactions. Considering the major
      role of extrinsic initiation in blood coagulation in vivo, we studied the
      material related-induction of this pathway by investigating the relevance of
      surface properties for the expression of Tissue Factor (TF), a critical initiator
      of the extrinsic pathway of coagulation. We incubated materials with self
      assembled monolayers of alkylthiols (SAMs) displaying various ratios of -CH(3), 
      OH, and -COOH terminations with fresh heparinized whole human blood in vitro. The
      transcription of TF-mRNA in leukocytes showed clear differences in relation to
      surface properties and increased over time. In addition, a positive correlation
      between TF transcription and its presence on leukocytes, granulocyte activation,
      and complement activation was found. Cells displaying the highest TF expression
      after material contact had significantly lower intracellular TF, pointing to
      previous TF release. Yet under the conditions of our whole blood incubation set
      up within the limited time frame the observed initiation of the extrinsic pathway
      did not trigger blood coagulation.

PMID- 20035992
TI  - Long term performance of small-diameter vascular grafts made of a
      poly(ether)urethane-polydimethylsiloxane semi-interpenetrating polymeric network.
AB  - In the past years considerable research efforts have been directed at developing
      more suitable synthetic vascular grafts, but small-diameter vascular grafts
      (SDVGs) perform less well than autogenous arterial or venous grafts. Grafts such
      as Dacron and ePTFE have often been used as alternatives to autologous grafts,
      but they have shown poor patency rates when used in small-diameter sizes or low
      flow locations. Nevertheless, despite these efforts no alternative concepts have
      emerged yet that promises to replace the current generation of synthetic grafts
      soon. The purpose of this preliminary in vivo study was to assess the blood and
      tissue compatibility behaviors of a novel compliant SDVGs, fabricated with a
      poly(ether)urethane-polydimethylsiloxane (PEtU-PDMS) semi-interpenetrating
      polymeric network (semi-IPN) and featuring two different porous layers in the
      wall thickness. Grafts were implanted according to anastomotic techniques which
      emulate the flow conditions clinically adopted for peripheral or aorto-coronary
      bypass procedures. Relatively long grafts were implanted in the common carotid
      artery of adult sheep and compared to standard ePTFE grafts of the same size and
      length implanted controlaterally. The animal experimentation showed superior
      handling and compliance characteristics, and patency rates of PEtU-PDMS grafts in
      comparison with a standard ePTFE graft, and the ability of remodelling in vivo
      while being gradually replaced by a natural tissue with no sign of calcification.

PMID- 20035993
TI  - The linker-free covalent attachment of collagen to plasma immersion ion
      implantation treated polytetrafluoroethylene and subsequent cell-binding
      activity.
AB  - It is desirable that polymers used for the fabrication of prosthetic implants
      promote biological functions such as cellular adhesion, differentiation and
      viability. In this study, we have used plasma immersion ion implantation (PIII)
      to modify the surface of polytetrafluoroethylene (PTFE), thereby modulating the
      binding mechanism of collagen. The amount of collagen bound to the polymer
      surface following PIII-treatment was similar to that bound by non-covalent
      physisorption. In a manner consistent with previous enzyme and tropoelastin
      binding data, the collagen bound to the PIII-treated PTFE surface was resistant
      to sodium dodecyl sulfate (SDS) elution whilst collagen bound to the untreated
      surface was fully removed. This demonstrates the capability of PIII-treated
      surfaces to covalently attach collagen without employing chemical linking
      molecules. Only the collagen bound to the PIII-treated PTFE surface supported
      human dermal fibroblast attachment and spreading. This indicates that collagen on
      the PIII-treated surface possesses increased adhesive activity as compared to
      that on the untreated surface. Cell adhesion was inhibited by EDTA when the
      collagen was bound to PIII-treated PTFE, as expected for integrin involvement.
      Additionally this adhesion was sensitive to the conformation of the bound
      collagen. Increased actin cytoskeletal assembly was observed on cells spreading
      onto collagen-coated PIII-treated PTFE compared to the collagen-coated untreated
      PTFE. These data demonstrate the retention of collagen's biological properties
      following its attachment to PIII-treated PTFE, suggesting advantages for tissue
      engineering and prosthetic design.

PMID- 20035994
TI  - Silencing of proinflammatory genes targeted to peritoneal-residing macrophages
      using siRNA encapsulated in biodegradable microspheres.
AB  - One of the more substantial hurdles to be overcome in realizing the exciting
      potential of siRNA molecules as therapeutic agents for a wide range of diseases
      is the intact delivery of the active molecule into its target cell. Here, we
      present a platform for in vitro and in vivo delivery and intracellular release of
      siRNA in peritoneal macrophages (Mvarphis). The delivery platform is based on the
      encapsulation of siRNA in biodegradable poly(d,l-lactide) (PLA) microspheres,
      which are targeted to Mvarphis by the simple principle of size exclusion. Proof
      of concept was achieved using siRNAs targeting TNFalpha and CD86 in macrophages.
      We show that the release of the siRNA in peritoneal-derived macrophages in vitro
      occurs intracellularly, and is abrogated by cytochalasin B, a phagocytosis
      inhibitor. Silencing in these cells is potent and lasts for at least one week. In
      vivo, we prove that siRNA encapsulated in biodegradable PLA microspheres can be
      delivered to peritoneal-residing Mvarphis and can induce potent silencing of
      TNFalpha secretion for at least one week. The PLA microspheres hold great
      potential for in vivo use, due to their biocompatibility and degradability, and
      can potentially be used for in vivo immunomodulation of Mvarphis for treatment of
      autoimmune and chronic inflammatory conditions.

PMID- 20035995
TI  - The effect of alternative neuronal differentiation pathways on PC12 cell adhesion
      and neurite alignment to nanogratings.
AB  - During development and regeneration of the mammalian nervous system, directional
      signals guide differentiating neurons toward their targets. Soluble neurotrophic
      molecules encode for preferential direction over long distances while the local
      topography is read by cells in a process requiring the establishment of focal
      adhesions. The mutual interaction between overlapping molecular and topographical
      signals introduces an additional level of control to this picture. The role of
      the substrate topography was demonstrated exploiting nanotechnologies to generate
      biomimetic scaffolds that control both the polarity of differentiating neurons
      and the alignment of their neurites. Here PC12 cells contacting nanogratings made
      of copolymer 2-norbornene ethylene (COC), were alternatively stimulated with
      Nerve Growth Factor, Forskolin, and 8-(4-chloro-phenylthio)-2'-O-methyladenosine
      3',5'-cyclic (8CPT-2Me-cAMP) or with a combination of them. Topographical
      guidance was differently modulated by the alternative stimulation protocols
      tested. Forskolin stimulation reduced the efficiency of neurite alignment to the
      nanogratings. This effect was linked to the inhibition of focal adhesion
      maturation. Modulation of neurite alignment and focal adhesion maturation upon
      Forskolin stimulation depended on the activation of the MEK/ERK signaling but
      were PkA independent. Altogether, our results demonstrate that topographical
      guidance in PC12 cells is modulated by the activation of alternative neuronal
      differentiation pathways.

PMID- 20035996
TI  - Enhancement of osteoblast adhesion to UV-photofunctionalized titanium via an
      electrostatic mechanism.
AB  - The mechanism underlying the recently found photofunctionalization of titanium is
      unknown. We focused on how the initial interaction between the cells and
      photofunctionalized titanium is enhanced at a molecular-level and the role played
      by the electrostatic status of the titanium surfaces in the possible regulatory
      mechanism for determining their bioactivity. Rat bone marrow-derived osteoblasts
      were cultured on untreated and ultraviolet (UV)-treated titanium surfaces. UV
      treatment converted the titanium surfaces from hydrophobic to superhydrophilic.
      The number of osteoblasts attached to UV-treated titanium surfaces was
      substantially greater than that attached to untreated surfaces (5-fold and 2-fold
      after 3 and 24 h of incubation, respectively). Osteoblasts cultured for 3 and 24
      h on these titanium surfaces were detached mechanically by vibrational force and
      enzymatically by trypsin treatment. Cell adhesion evaluated by the percentage of
      remaining cells after these detachments was substantially greater for cells on UV
      treated titanium surfaces compared to untreated titanium surfaces (110-120%
      greater for cells incubated for 3 h and 50-60% greater for cells incubated for 24
      h). Osteoblasts on UV-treated surfaces expressed more vinculin. UV-enhancing
      effect in cell adhesion was also demonstrated under a serum-free condition. UV
      enhanced cell adhesion was abrogated when the UV-treated titanium surfaces were
      electrostatically neutralized by either removing the electric charge or masking
      with monovalent anions, while the surfaces maintained superhydrophilicity. In
      conclusion, the establishment of osteoblast adhesion is accelerated and augmented
      remarkably on UV-treated titanium surfaces, associated with upregulated
      expression of vinculin. This study has identified an electrostatic property of UV
      treated titanium surfaces playing a regulatory role in determining their
      bioactivity, superseding the effect of the hydrophilic nature of these surfaces.
      A mechanism underlying the UV-induced conversion of titanium from bioinert to
      bioactive, in which direct cell-titanium interaction is exclusively enabled, is
      proposed.

PMID- 20035997
TI  - The use of nanodiamond monolayer coatings to promote the formation of functional
      neuronal networks.
AB  - Nanostructured materials provide a new dimension of interaction with biological
      systems that takes place on a sub-cellular level with a high degree of
      specificity. In the field of neuroscience the nanoscale corresponds to the size
      of synapses; the specific connections between brain cells. In this context,
      diamond-based materials have attracted much attention due to their extreme
      mechanical and electrical properties and their chemical inertness. Here the
      suitability of nanodiamond (ND) monolayers to act as a platform for neuronal
      growth is investigated. Neurons cultured on various ND-coated substrates perform
      remarkably well, and similar to those grown on standard protein-coated materials
      with respect to their initial cell attachment, sustained neurite outgrowth, cell
      autonomous neuronal excitability and functionality of the resulting electrical
      networks. ND layering provides an excellent growth substrate on various materials
      for functional neuronal networks and bypasses the necessity of protein coating,
      which promises great potential for chronic medical implants.

PMID- 20035998
TI  - A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal
      contrast agent.
AB  - Multi-modal molecular imaging can significantly improve the potential of non
      invasive medical diagnosis by combining basic anatomical descriptions with in
      depth phenotypic characteristics of disease. Contrast agents with multifunctional
      properties that can sense and enhance the signature of specific molecular
      markers, together with high biocompatibility are essential for combinatorial
      molecular imaging approaches. Here, we report a multi-modal contrast agent based
      on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous
      contrast enhancement for three major molecular imaging techniques such as
      magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR)
      fluorescence imaging. Monodispersed nHAp crystals of average size approximately
      30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth
      impurities by a surfactant-free, aqueous wet-chemical method at 100 degrees C.
      Doping of nHAp with Eu(3+) (3 at%) resulted bright near-infrared fluorescence
      (700 nm) due to efficient (5)D(0)-(7)F(4) electronic transition and co-doping
      with Gd(3+) resulted enhanced paramagnetic longitudinal relaxivity (r(1)
      approximately 12 mM(-1) s(-1)) suitable for T(1) weighted MR imaging together
      with approximately 80% X-ray attenuation suitable for X-ray contrast imaging.
      Capability of MF-nHAp to specifically target and enhance the signature of
      molecular receptors (folate) in cancer cells was realized by carbodiimide
      grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface
      aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp
      conjugates showed specific aggregation on FR(+ve) cells while leaving the
      negative control cells untouched. Nanotoxicity evaluation of this multifunctional
      nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung
      fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung
      cancer cell line (A549) revealed no apparent toxicity even upto relatively higher
      doses of 500 microg/mL and 48 h of incubation. Flow-cytometry based reactive
      oxygen species (ROS) analysis also showed no significant levels of ROS generation
      in the nHAp treated cells. The tri-modal contrast imaging functionality together
      with molecular receptor targeting capability and biocompatibility makes MF-nHAp a
      promising biomineral contrast agent for combinatorial molecular imaging.

PMID- 20035999
TI  - Lyophilized HER2-specific PEGylated immunoliposomes for active siRNA gene
      silencing.
AB  - The development of a tumor-specific immunoliposome delivering small interfering
      RNA (siRNA) represents a practical way in cancer gene therapy. In this study, we
      developed PEGylated 3beta-[N-(N', N'-dimethylaminoethane) carbamoyl] cholesterol
      (DC-Chol)/dioleoylphosphatidyl ethanolamine (DOPE) immunoliposomes conjugated
      with the Fab' of recombinant humanized anti-HER2 monoclonal antibody (PIL) for
      siRNA delivery. The results demonstrated that the lyophilized PIL (LPIL) prepared
      by the lyophilization/rehydration method possessed a significantly enhanced HER1
      gene, a model target, silencing ability compared with PIL in HER2-overexpressing
      SK-BR3 cells. Among a series of LPIL with different PEGylation degree, LPIL
      containing 2.5%PEG (2.5%PEG LPIL) showed the best HER1 gene silencing activity.
      Confocal microscope studies demonstrated that 2.5%PEG LPIL could specifically
      bind to SK-BR3 cells and were sequentially internalized into them. Using RhoA as
      a cancer therapeutic target, 2.5%PEG LPIL entrapping anti-RhoA siRNA could
      specifically silence RhoA expression and inhibit cell invasion in SK-BR3 cells.
      In conclusion, these finding demonstrated the potential use of 2.5%PEG LPIL in
      specifically delivering siRNA to HER2-overexpressing cancers.

PMID- 20036001
TI  - A system for optical high resolution screening of electrical excitable cells.
AB  - The application of primary excitable cells for high content screening (HCS)
      requires a multitude of novel developments including cell culture and multi-well
      plates. Here we introduce a novel system combining optimised culture conditions
      of primary adult cardiomyocytes with the particular needs of excitable cells for
      arbitrary field stimulation of individual wells. The major advancements of our
      design were tested in calcium imaging experiments and comprise (i) each well of
      the plate can be subjected to individual pulse protocols, (ii) the software
      driving electrical stimulation can run as a stand-alone application but also as a
      plug-in in HCS software packages, (iii) the optical properties of the plastic
      substrate (foil) resemble those of glass coverslips fostering high resolution
      immersion-based microscopy, (iv) the bottom of the foil is coated with an
      oleophobic layer that prevents immersion oil from sticking, (v) the top of the
      foil is coated with an elastic film. The latter enables cardiomyocytes to display
      loaded contractions by mimicking the physiologically occurring local elastic
      network (e.g. extracellular matrix) and results in significantly increased
      contractions (with identical calcium transients) when compared to non-elastic
      substrates. Thus, our novel design and culture conditions represent an essential
      further step towards the application of primary cultured adult cardiomyocytes for
      HCS applications.

PMID- 20036000
TI  - Photoacoustic imaging of living mouse brain vasculature using hollow gold
      nanospheres.
AB  - Photoacoustic tomography (PAT) also referred to as optoacoustic tomography (OAT)
      is a hybrid imaging modality that employs nonionizing optical radiation and
      ultrasonic detection. Here, we describe the application of a new class of optical
      contrast agents based on mesoscopic hollow gold nanospheres (HAuNS) to PAT. HAuNS
      are approximately 40 nm in diameter with a hollow interior and consist of a thin
      gold wall. They display strong resonance absorption tuned to the near-infrared
      (NIR) range, with an absorption peak at 800 nm, whose photoacoustic efficiency is
      significantly greater than that of blood. Following surface conjugation with
      thiolated poly(ethylene glycol), the pegylated HAuNS (PEG-HAuNS) had distribution
      and elimination half-lives of 1.38 +/- 0.38 and 71.82 +/- 30.46 h, respectively.
      Compared with PAT images based on the intrinsic optical contrast in nude mice,
      the PAT images acquired within 2 h after intravenous administration of PEG-HAuNS
      showed the brain vasculature with greater clarity and detail. The image depicted
      brain blood vessels as small as approximately 100 mum in diameter using PEG-HAuNS
      as contrast agents. Preliminary results showed no acute toxicity to the liver,
      spleen, or kidneys in mice following a single imaging dose of PEG-HAuNS. Our
      results indicate that PEG-HAuNS are promising contrast agents for PAT, with high
      spatial resolution and enhanced sensitivity.

PMID- 20036002
TI  - Kinins in cardiac inflammation and regeneration: insights from ischemic and
      diabetic cardiomyopathy.
AB  - The kallikrein-kinin system (KKS) is a system of vasoactive peptides, the kinins,
      involved in different aspects of remodeling, inflammation and angiogenesis.
      Kinins mediate their actions through two receptors, B1R and B2R. It is
      increasingly recognized that the KKS is involved in the inflammatory processes of
      the heart. Evidence shows that the B2R is beneficial in myocardial diseases,
      protecting from inflammation, fibrosis and apoptosis, while B1R shows a
      proinflammatory character contributing to the disease progression by increasing
      the production of cytokines and stimulating the migration of immune cells.
      Furthermore, novel important actions of the KKS and its receptors contribute to
      neovascularization and recruitment of endothelial progenitor cells in ischemic
      areas and endothelial dysfunction. The kinin receptors could therefore constitute
      potential therapeutic targets in the treatment of myocardial ischemia and
      diabetic cardiomyopathy.

PMID- 20036003
TI  - Neuronal circuits involving ghrelin in the hypothalamus-mediated regulation of
      feeding.
AB  - Ghrelin, an n-octanoylated 28-amino acid brain-gut peptide, was first isolated
      from extracts of porcine stomach. Ghrelin is an endogenous ligand for the growth
      hormone secretagogue type 1a receptor (GHS-R1a), the functionally active form of
      GHS-R, and stimulates feeding and growth hormone secretion. Ghrelin is mainly
      produced in the A/X-like cells of the oxyntic glands of the stomach and is the
      main orexigenic circulating hormone that acts on the hypothalamus to affect
      feeding behavior and energy metabolism. Ghrelin-containing neuronal cell bodies
      are localized in the hypothalamic arcuate nucleus, a center that integrates
      signals for energy homeostasis. Ghrelin-containing nerve fibers are widely
      distributed in the brain. Accumulated evidence shows that hypothalamic
      neuropeptides such as neuropeptide Y (NPY), orexin and proopiomelanocortin (POMC)
      are involved in the regulation of feeding behavior and energy homeostasis via
      neuronal circuits in the hypothalamus. Ghrelin also forms part of the feeding
      regulating neuronal circuitry in conjunction with other feeding-regulating
      peptide-containing neurons within the hypothalamus. In view of the fact that one
      decade has now passed since ghrelin was first discovered, we review advances that
      have been made in ghrelin research during that time and how this has impacted on
      our knowledge of feeding regulation in the hypothalamus. We also summarize our
      current understanding of the neuronal interactions between ghrelin and the
      different kinds of feeding-regulating peptide-containing neurons in the
      hypothalamus based on evidence at the ultrastructural level.

PMID- 20036004
TI  - Ezrin is a key molecule in the metastasis of MOLT4 cells induced by CCL25/CCR9.
AB  - Chemokines and their corresponding receptors participate in transmigration of
      leukemic cells. ERM (ezrin/radixin/moesin) protein family act as linkers between
      the plasma membrane and the cytoskeleton and are key component in tumor
      metastasis. In this study we used the CCR9-expressing acute T lymphocytic cell
      line MOLT4 as a model and assesssed their morphological and functional changes in
      response to CCL25. The pseudopodium formed and ERM translocated from the
      cytoplasm to the cell membrane following treatment with CCL25. Ezrin silencing by
      miRNA showed that ezrin plays important roles in the polarization and invasive
      behaviour of MOLT4 cells.

PMID- 20036005
TI  - Gene expression profile of protein kinases reveals a distinctive signature in
      chronic lymphocytic leukemia and in vitro experiments support a role of second
      generation protein kinase inhibitors.
AB  - To investigate the role of protein kinases (PKs) in chronic lymphocytic leukemia
      (CLL), we performed gene expression profile on 505 PK genes. Comparison between
      CLL with acute lymphocytic leukemia (ALL) patients highlighted an homogeneous up
      modulation of several PKs in CLL, 16 also overexpressed in two additional CLL
      cohorts. Q-PCR analysis confirmed these findings. No differences were observed in
      the main prognostic subclasses, indicating that PK overexpression is specific of
      the disease itself. Tests in vitro showed that Dasatinib partially reduced CLL
      cells viability, mostly in IGHV germline patients. These findings suggest that
      treatment with second generation tyrosine kinase (TK) inhibitors may represent an
      attractive therapeutic strategy for CLL patients.

PMID- 20036006
TI  - Contaminant fate and transport in the Venice Lagoon: results from a multi-segment
      multimedia model.
AB  - Contaminant loadings to the Venice Lagoon peaked from 1950s-1980s and although
      they have since declined, contaminant concentrations remain elevated in sediment
      and seafood. In order to identify the relative importance of contaminant sources,
      inter-media exchange and removal pathways, a modified 10-segment
      fugacity/aquivalence-based model was developed for octachlorodibenzodioxin/furan
      (OCDD/F), PCB-180, Pb and Cu in the Venice Lagoon. Results showed that in-place
      pollution nearby the industrial area, current industrial discharges, and
      tributary loadings were the main sources of contaminants to the lagoon, with
      negligible contributions from the atmosphere. The fate of these contaminants was
      governed by sediment-water exchange with simultaneous advective transport by
      water circulation. Contaminants circulated amongst the northern and central
      basins with a small fraction reaching the far southern basin and the Chioggia
      inlet. As a consequence, we estimated limited contaminant transfer to the
      Adriatic Sea, trapping the majority of contaminants in the sediment in this
      "average" circulation scenario which does not account for periodic flooding
      events.

PMID- 20036007
TI  - Substance use, mental health, and relationships: A comparison of male and female
      offenders serving community sentences.
AB  - This study examined criminogenic need in the areas of drug use, alcohol use,
      mental health, and relationships, in 6453 male and 1045 female probationers,
      using data from the Offender Assessment System (OASys). It also examined the
      associations between these four areas. Females had significantly higher levels of
      need than males for mental health and relationships, and males had significantly
      higher levels of need for alcohol use. There was no group difference for drug
      use. For both males and females, there were significant positive correlations for
      scores between all pairs of needs, except for drug and alcohol use. The strength
      of the association between relationships and drug use was significantly stronger
      among females as compared to males. The results are discussed in light of the
      previous research and their implications for interventions to reduce offending.

PMID- 20036008
TI  - Frequency of distinguishing clinical features in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To determine the frequency of occurrence of limited clinical features
      which distinguish patients with Vogt-Koyanagi-Harada (VKH) disease from those
      with non-VKH uveitis. DESIGN: Comparative case series. PARTICIPANTS: We included
      1147 patients. METHODS: All patients with bilateral ocular inflammatory disease
      presenting to any of 10 uveitis centers in the 3-month period between January 1
      and March 31, 2006 (inclusive), were asked to participate. The clinical and
      historical features of disease were obtained from the participants via direct
      interview and chart review. Patients were stratified based on whether they were
      diagnosed with VKH disease or non-VKH uveitis for statistical analysis. MAIN
      OUTCOME MEASURES: Presence or absence of various clinical features in the 2
      populations. RESULTS: Of 1147 patients, 180 were diagnosed with VKH disease and
      967 with non-VKH uveitis. Hispanics and Asians were more likely to be diagnosed
      with VKH than non-VKH disease compared with other ethnicities. In acute disease,
      the finding of exudative retinal detachment was most likely to be found in VKH
      disease with a positive predictive value (PPV) of 100 and negative predictive
      value (NPV) of 88.4, whereas in chronic disease, sunset glow fundus was most
      likely to be found, with a PPV of 94.5 and NPV of 89.2. CONCLUSIONS: Numerous
      clinical findings have been described in the past as important in the diagnosis
      of VKH. The current study reveals that of these, 2 are highly specific to this
      entity in an ethnically and geographically diverse group of patients with
      nontraumatic bilateral uveitis. These clinical findings are exudative retinal
      detachment during acute disease and sunset glow fundus during the chronic phase
      of the disease.

PMID- 20036009
TI  - Nonaccidental trauma and peripheral retinal nonperfusion.
AB  - PURPOSE: To present fluorescein angiographic findings demonstrating retinal
      vascular alterations in children subjected to nonaccidental trauma (NAT). DESIGN:
      Retrospective non-comparative consecutive case series. PARTICIPANTS: Ten eyes of
      5 children with the diagnosis of NAT seen at William Beaumont Hospital between
      August 2007 and December 2008. METHODS: We retrospectively reviewed the charts of
      5 consecutive patients with NAT. All patients underwent detailed ophthalmic
      evaluation under anesthesia, fundus photography, and fluorescein angiography
      (FA). MAIN OUTCOME MEASURES: The primary outcome was FA findings demonstrating
      alterations in retinal vascular perfusion, retinal neovascularization, and
      traction retinal detachment. RESULTS: Seven of 10 eyes demonstrated peripheral
      retinal nonperfusion by FA, with interruption of both the arterial- and venous
      side of the retinal vascular tree. All of the eyes with retinal nonperfusion also
      presented with preretinal and/or vitreous hemorrhage; none of the eyes without
      ischemia demonstrated preretinal or vitreous blood. None of the children were
      born prematurely or had a medical or family history that could otherwise explain
      their findings. None of the eyes exhibited neovascularization or retinal
      detachment. Two eyes were treated with laser photocoagulation alone; 2 eyes were
      treated with vitrectomy alone owing to a nonclearing premacular hemorrhage; 2
      eyes were treated with vitrectomy and laser photocoagulation; and 1 eye was
      observed without treatment. CONCLUSIONS: Peripheral retinal nonperfusion was
      noted by FA in 7 eyes of infants who were victims of nonaccidental head trauma.
      Preretinal and/or vitreous hemorrhage may be associated with the development of
      retinal nonperfusion. Physicians may consider FA in children with known or
      suspected NAT. The role of prophylactic laser treatment is unclear, and close
      observation for the development of neovascularization is warranted.

PMID- 20036010
TI  - Agreement for detecting glaucoma progression with the GDx guided progression
      analysis, automated perimetry, and optic disc photography.
AB  - PURPOSE: To evaluate the ability of the GDx Variable Corneal Compensation (VCC)
      Guided Progression Analysis (GPA) software for detecting glaucomatous
      progression. DESIGN: Observational cohort study. PARTICIPANTS: The study included
      453 eyes from 252 individuals followed for an average of 46+/-14 months as part
      of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes
      were classified as glaucomatous, 67% of the eyes were classified as suspects, and
      5% of the eyes were classified as healthy. METHODS: Images were obtained annually
      with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA
      software. Progression using conventional methods was determined by the GPA
      software for standard automated achromatic perimetry (SAP) and by masked
      assessment of optic disc stereophotographs by expert graders. MAIN OUTCOME
      MEASURES: Sensitivity, specificity, and likelihood ratios (LRs) for detection of
      glaucoma progression using the GDx GPA were calculated with SAP and optic disc
      stereophotographs used as reference standards. Agreement among the different
      methods was reported using the AC(1) coefficient. RESULTS: Thirty-four of the 431
      glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc
      stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of
      50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of
      96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the
      healthy eyes showed progression by the GDx GPA, with a specificity of 100% in
      this group. Inter-method agreement (AC(1) coefficient and 95% confidence
      intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44
      (0.28-0.61), respectively. CONCLUSIONS: The GDx GPA detected glaucoma progression
      in a significant number of cases showing progression by conventional methods,
      with high specificity and high positive LRs. Estimates of the accuracy for
      detecting progression suggest that the GDx GPA could be used to complement
      clinical evaluation in the detection of longitudinal change in glaucoma.

PMID- 20036011
TI  - Cigarette smoking as a risk factor for uveitis.
AB  - PURPOSE: To determine the association between tobacco smoking history and
      uveitis. DESIGN: Retrospective, case-control study. PARTICIPANTS: A total of 564
      patients with ocular inflammation seen in the Proctor Foundation uveitis clinic
      between 2002 and 2009, and 564 randomly selected patients seen in the
      comprehensive eye clinic within the same time period. METHODS: A retrospective
      medical record review of all cases and controls. MAIN OUTCOME MEASURES: A
      logistic regression analysis was conducted with ocular inflammation as the main
      outcome variable and smoking as the main predictor variable, while adjusting for
      age, gender, race, and median income. RESULTS: The odds of a smoker having ocular
      inflammation were 2.2-fold that of a patient who had never smoked (95% confidence
      interval [CI], 1.7-3.0; P<0.001). All anatomic subtypes of uveitis were
      associated with a positive smoking history, with odds ratios (ORs) of 1.7 (95%
      CI, 1.2-2.4; P = 0.002) for anterior uveitis, 2.7 (95% CI, 1.4-5.6; P = 0.005)
      for intermediate uveitis, 3.2 (95% CI, 1.3-7.9; P = 0.014) for posterior uveitis,
      and 3.9 (95% CI, 2.4-6.1; P<0.001) for panuveitis. In patients with panuveitis
      and cystoid macular edema (CME), the OR was 8.0 (95% CI, 3.3-19.5; P<0.001)
      compared with 3.1 (95% CI, 1.8-5.2; P<0.001) for patients without CME. Patients
      with intermediate uveitis and CME also had a higher OR (OR 8.4; 95% CI, 2.5-28.8;
      P = 0.001) compared with patients without CME (OR 1.5; 95% CI, 0.6-3.8; P =
      0.342). Patients with a smoking history were at greater odds of having infectious
      uveitis (OR 4.5; 95% CI, 2.3-9.0; P<0.001) than noninfectious uveitis (OR 2.1;
      95% CI, 1.6-2.8; P<0.001), although both were associated with smoking.
      CONCLUSIONS: A history of smoking is significantly associated with all anatomic
      subtypes of uveitis and infectious uveitis. The association was greater in
      patients with intermediate uveitis and panuveitis with CME compared with those
      without CME. In view of the known risks of smoking, these findings, if
      replicated, would give an additional reason to recommend smoking cessation in
      patients with uveitis.

PMID- 20036012
TI  - Increased tissue endothelin-1 and endothelin-B receptor expression in temporal
      arteries from patients with giant cell arteritis.
AB  - PURPOSE: Endothelin (ET)-1 has been implicated in the atherosclerotic process and
      during inflammation. Similarity in the development process of giant cell
      arteritis (GCA) and atherosclerosis exists. Several ET receptor antagonists have
      been developed, principally to target cardiovascular disease states. High doses
      of corticosteroids currently are used in the treatment of GCA, whereas other
      treatments are not as reliably effective. The present study was performed to
      elucidate the role for ET-1, ET(A), and ET(B) receptors in GCA. DESIGN:
      Experimental, retrospective immunohistochemical study of temporal arteries using
      archival formalin-fixed, paraffin-embedded tissue. PARTICIPANTS: The study
      included 10 patients with GCA and 10 control patients with clinically suspected
      GCA but diagnosed not to have GCA. METHODS: Immunohistochemistry, with anti ET-1,
      anti-ET(A), and anti-ET(B) antibodies, was performed on formalin-fixed and
      paraffin-embedded temporal arteries. MAIN OUTCOME MEASURES: Endothelin-1, ET(A),
      and ET(B) receptor immunostaining intensities were quantified. RESULTS: Temporal
      arteries from the patients with GCA showed the typical histologic features,
      including intimal thickening, disruption or loss of the elastic lamina, and
      inflammatory infiltrates of lymphocytes, macrophages, and multinucleated giant
      cells. These features were associated with increased ET-1 and ET(B) receptor
      immunoreactivity in the medial layer of the temporal arteries and endothelial
      cells in patients with GCA compared with the controls. The increased ET-1 and
      ET(B) receptor immunoreactivity occurred in vascular smooth muscle cells (SMCs)
      and multinucleated giant cells. The ET-1 and ET(B) receptor immunoreactivity
      correlated with the degree of systemic inflammation. No changes were observed in
      ET(A) receptor expression in SMCs or endothelial cells compared with controls.
      CONCLUSIONS: The results suggest a role for ET-1 and ET(B) receptors in GCA.
      Inhibiting the ET system may provide a corticosteroid-sparing alternative in the
      treatment of GCA.

PMID- 20036013
TI  - Retinopathy in persons without diabetes: the Handan Eye Study.
AB  - PURPOSE: To describe the prevalence and associations of retinopathy in a
      population-based nondiabetic sample of rural Chinese. DESIGN: Population-based
      cross-sectional study. PARTICIPANTS: We included 6830 Han Chinese aged > or =30
      years from 13 villages of Yongnian County, Handan City, Hebei Province, China.
      METHODS: All participants underwent a standardized interview and extensive
      examinations including retinal photography, measurement of blood pressure (BP)
      and fasting plasma glucose (FPG). Diabetes mellitus was defined as either FPG >
      or = 7.0 mmol/l, use of diabetic medication or a physician diagnosis of diabetes.
      Photographic grading of retinopathy followed the modified Early Treatment
      Diabetic Retinopathy Study classification system. Logistic regression models were
      used to assess associations of retinopathy. MAIN OUTCOME MEASURES: Any
      retinopathy. RESULTS: The prevalence of retinopathy among participants without
      diabetes was 13.6% (95% confidence interval [CI], 12.6-14.6%). The age and gender
      standardized prevalence of retinopathy in the Chinese adult population (aged 30+
      years) without diabetes was estimated to be 12.1% (95% CI 11.1-12.9%).
      Independent risk factors associated with retinopathy were age (odds ratio [OR],
      1.02 ; 95% CI 1.01-1.03 per year increase), male gender (male vs. female, OR
      1.27; 95% CI 1.08-1.49), higher FPG (OR 1.30; 95% CI 1.11-1.53 per mmol/l
      increase), higher systolic BP (OR 1.15; 95% CI 1.05-1.27 per 10 mmHg increase)
      and higher diastolic BP (OR 1.16; 95% CI 1.09-1.22 per 10 mmHg increase).
      CONCLUSIONS: Retinopathy was common among rural Chinese adults without diabetes.
      Its association with FPG and BP suggests that early microvascular damage is
      occurring at "high normal" levels of blood glucose and BP.

PMID- 20036015
TI  - Oxidative stress in Egyptian children with autism: relation to autoimmunity.
AB  - We are the first to study the relationship between oxidative stress (by measuring
      plasma F2-isoprostane, as a marker of lipid peroxidation, and glutathione
      peroxidase, as an antioxidant enzyme) and autoimmunity (as indicated by serum
      antineuronal antibodies) in a group of 44 Egyptian autistic children and 44
      healthy matched-children. Our results showed that oxidative stress was found in
      88.64% of autistic children. Oxidative stress, resulting from elevated plasma F2
      isoprostane and/or reduced glutathione peroxidase, had significant risk for
      antineuronal positivity, which was found in 54.5% of autistic children, (odds
      ratio: 12.38 and 6.43, respectively, confidence interval: 1.37-112.10 and 1.21
      34.19, respectively). CONCLUSIONS: the strong association between oxidative
      stress and autoimmunity in autistic children may indicate the possible role of
      oxidative stress, through induction of autoimmunity, in some autistic patients.
      Therefore, studies considering the role of antioxidants and immunotherapy in
      amelioration of autistic manifestations are recommended.

PMID- 20036016
TI  - UK and Ireland experience of cochlear implants in children with Down syndrome.
AB  - OBJECTIVES: Down Syndrome (DS) is associated with a high incidence of hearing
      loss. The majority of hearing loss is conductive, but between 4 and 20% is
      sensorineural, which in the main is mild or moderate and is managed with
      conventional behind-the-ear hearing aids. Cochlear implantation is an elective
      invasive procedure, performed to provide some form of hearing rehabilitation in
      individuals with severe to profound sensorineural hearing loss, and initially
      candidacy criteria were strict--excluding patients with additional disabilities.
      With good results and expanding experience, more candidates with additional
      disabilities are now being implanted. A survey of UK and Ireland Cochlear Implant
      Programmes sought to identify the number of individuals with DS who have been
      implanted with a cochlear implant (CI) and to provide relevant information on
      outcomes of implantation in these individuals. METHODS: E-mail survey of all
      programmes within the British Cochlear Implant Group (BCIG). Postal questionnaire
      to programmes identified to have implanted a child with Down Syndrome, with data
      collection on pre-operative assessment, surgical and post-operative outcomes.
      Case series review. RESULTS: Three of 23 BCIG programmes have implanted a child
      with Down Syndrome. Four children have received implants. No intraoperative or
      post-operative surgical complications were encountered. All children had middle
      ear disease, but no problems with implantation were associated with their middle
      ear condition. All children remain implant users, 12 months to 4 years post
      implantation. CONCLUSION: Cochlear implantation is an option for a child with
      Down Syndrome and associated severe to profound sensorineural hearing loss.
      Clinicians caring for these children and their families should consider referral
      for assessment by a Cochlear Implant Programme.

PMID- 20036014
TI  - Characterization and modulation of canine mast cell derived eicosanoids.
AB  - Mast cells play an important role in both innate and acquired immunity as well as
      several pathological conditions including allergy, arthritis and neoplasia. They
      influence these processes by producing a variety of mediators including
      cytokines, chemokines and eicosanoids. Very little is currently known about the
      spectrum of inflammatory mediators, particularly eicosanoids (prostaglandins and
      leukotrienes), produced by canine mast cells. This is important since modulating
      mast cell derived eicosanoids may help in the treatment of autoimmune and
      inflammatory disorders. The purpose of this study was to investigate the spectrum
      of eicosanoids produced by normal canine mast cells and to evaluate the effects
      of cytokines and non-steroidal anti-inflammatory mediators (NSAIDS) on eicosanoid
      production and release. Canine bone marrow derived cultured mast cells (cBMCMCs)
      expressed COX-1, COX-2, and 5-LOX and synthesized and released PGD2, PGE2, LTB4,
      and LTC4 following activation by a variety of stimuli. The selective COX-2 NSAIDs
      carprofen (Rimadyl) and deracoxib (Deramaxx) inhibited PGD2 and PGE2 production
      but only slightly inhibited LTB4 and LTC4. The mixed COX-1/COX-2 inhibitor
      piroxicam blocked PGD2 and PGE2 production, but upregulated LTC4 following
      treatment while tepoxilan (Zubrin), a pan COX/LOX inhibitor, markedly reduced the
      production of all eicosanoids. The LOX inhibitor nordihydroguaiaretic acid (NDGA)
      prevented LTB4/LTC4 release and BMBMC degranulation. Pre-incubation of cBMCMCs
      with IL-4 and SCF sensitized these cells to degranulation in response to
      substance P. In conclusion, canine BMCMCs produce an array of eicosanoids similar
      to those produced by mast cells from other species. Tepoxilan appeared to be the
      most effective NSAID for blocking eicosanoid production and thus may be useful
      for modulating mast cell mediated responses in dogs.

PMID- 20036017
TI  - Impact of arterial remodeling on high sensitive C-reactive protein after a DES
      implantation.
AB  - The inflammatory response after percutaneous coronary intervention (PCI) with
      stent between coronary lesions with positive (PR) and negative remodeling (NR)
      might be different. In 68 patients, the changes of the hs-CRP from baseline to 24
      h after PCI and the intimal hyperplasia (IH) volume at follow up were
      significantly higher in the PR. A positive correlation was noted between the
      changes of the hs-CRP from baseline to each stage (24 h and 72 h) and the IH
      volume. This prospective study showed that an increased IH in lesions with PR
      after PCI might be associated with an increased inflammatory response.

PMID- 20036018
TI  - Left ventricular twist and untwist in aortic stenosis.
AB  - BACKGROUND: To optimally exploit the potential added diagnostic and prognostic
      value of new left ventricular (LV) deformation parameters, better understanding
      of LV mechanics in aortic stenosis (AS) is warranted. We sought to determine a
      broad spectrum of LV rotation parameters in AS patients and age-matched healthy
      controls, in order to gain insight into the mechanical properties of the LV in
      AS. METHODS: The study comprised 48 AS patients with an aortic valve area<2.0 cm2
      and LV ejection fraction>50%, and 24 healthy--for age and gender matched--control
      subjects. LV peak systolic rotation (Rotmax), LV peak systolic twist (Twistmax),
      untwisting rate (mean diastolic untwisting velocity from Twistmax to mitral valve
      opening), peak diastolic untwisting velocity, and time-to-peak diastolic
      untwisting velocity were determined by speckle tracking echocardiography.
      RESULTS: AS patients had normal basal Rotmax and increased apical Rotmax,
      resulting in increased Twistmax (13.4+/-4.0 degrees  vs. 11.4+/-2.7 degrees ,
      P<0.05). Apical Rotmax and Twistmax correlated significantly to echo-Doppler
      indicators of AS severity. Time-to-peak diastolic untwisting velocity was
      increased (20+/-10% vs. 15+/-9%, P<0.05) and untwisting rate was decreased (-38+/
      21 degrees /s vs. -50+/-28 degrees /s, P<0.01) in AS patients. CONCLUSIONS:
      Twistmax increases proportionally to the severity of AS, which might serve as a
      compensatory mechanism to maintain systolic LV function. LV diastolic untwisting
      is delayed and the untwisting rate is reduced in AS.

PMID- 20036019
TI  - Effects of sugar-sweetened and sugar-free cocoa on endothelial function in
      overweight adults.
AB  - BACKGROUND: Studies of cocoa suggest an array of cardiovascular benefits;
      however, the effects of daily intake of sugar-free and sugar-sweetened cocoa
      beverages on endothelial function (EF) have yet to be established. METHODS: 44
      adults (BMI 25-35 kg/m2) participated in a randomized, controlled, crossover
      trial. Participants were randomly assigned to a treatment sequence: sugar-free
      cocoa beverage, sugar-sweetened cocoa beverage, and sugar-sweetened cocoa-free
      placebo. Treatments were administered daily for 6 weeks, with a 4-week washout
      period. RESULTS: Cocoa ingestion improved EF measured as flow-mediated dilation
      (FMD) compared to placebo (sugar-free cocoa: change, 2.4% [95% CI, 1.5 to 3.2]
      vs. -0.8% [95% CI, -1.9 to 0.3]; difference, 3.2% [95% CI, 1.8 to 4.6]; p<0.001
      and sugar-sweetened cocoa: change, 1.5% [95% CI, 0.6 to 2.4] vs. -0.8% [95% CI, 
      1.9 to 0.3]; difference, 2.3% [95% CI, 0.9 to 3.7]; p=0.002). The magnitude of
      improvement in FMD after consumption of sugar-free versus sugar-sweetened cocoa
      was greater, but not significantly. Other biomarkers of cardiac risk did not
      change appreciably from baseline. BMI remained stable throughout the study.
      CONCLUSIONS: Daily cocoa ingestion improves EF independently of other biomarkers
      of cardiac risk, and does not cause weight gain. Sugar-free preparations may
      further augment endothelial function.

PMID- 20036020
TI  - Circulating procoagulant microparticles in acute pulmonary embolism: a case
      control study.
AB  - We investigated whether circulating procoagulant microparticles (CPMPs)
      contributed to hypercoagulability in 45 patients with acute pulmonary embolism
      (APE) and in 45 controls with and 45 controls without cardiovascular risk
      factors. Concentrations of CPMPs and platelet-derived microparticles (PMPs) were
      statistically significantly higher in patients with APE than in controls without
      cardiovascular risk factors. PMPs appeared to be the main source of procoagulant
      microparticle release in APE, but this correlation disappeared when APE patients
      were compared to controls with cardiovascular risk factors. CPMPs may have a role
      in venous thrombosis as mediators of cardiovascular risk factors.

PMID- 20036021
TI  - Cytokines: potential contributors to arrhythmogenesis in demyelinating syndromes?
AB  - Neurological disorders including chronic demyelinating syndromes (CDSs) have been
      known to elicit propensity to cardiac arrhythmias possibly due to autonomic
      imbalance, myocardial myocytolysis and some psychological conditions (major
      depression etc.) associated with these syndromes. CDSs are generally
      characterized by variable degrees of inflammatory response that may corrrelate
      with clinical disease activity (relapse, progression etc.). In the clinical
      setting, enhanced inflammatory response as measured with increased levels of
      inflammatory markers may predispose to cardiac arrhythmias via direct or indirect
      mechanisms. Therefore, substantial levels of inflammatory markers including pro
      inflammatory cytokines associated with CDSs may serve as potential contributors
      to arrhythmogenesis indicating the possible link between disease activity and
      arrhythmia risk in patients with CDSs.

PMID- 20036022
TI  - Coronary artery ectasia: still an unknown phenomenon.

PMID- 20036023
TI  - Differential induction of apoptosis in human colonic carcinoma cells (Caco-2) by
      Atopobium, and commensal, probiotic and enteropathogenic bacteria: mediation by
      the mitochondrial pathway.
AB  - The induction of apoptosis in mammalian cells by bacteria is well reported. This
      process may assist infection by pathogens whereas for non-pathogens apoptosis
      induction within carcinoma cells protects against colon cancer. Here, apoptosis
      induction by a major new gut bacterium, Atopobium minutum, was compared with
      induction by commensal (Escherichia coli K-12 strains), probiotic (Lactobacillus
      rhamnosus, Bifidobacterium latis) and pathogenic (E. coli: EPEC and VTEC) gut
      bacteria within the colon cancer cell line, Caco-2. The results show a major
      apoptotic effect for the pathogens, mild effects for the probiotic strains and A.
      minutum, but no effect for commensal E. coli. The mild apoptotic effects observed
      are consistent with the beneficial roles of probotics in protection against colon
      cancer and suggest, for the first time, that A. minutum possesses similar
      advantageous, anti-cancerous activity. Although bacterial infection increased
      Caco-2 membrane FAS levels, caspase-8 was not activated indicating that apoptosis
      is FAS independent. Instead, in all cases, apoptosis was induced through the
      mitochondrial pathway as indicated by BAX translocation, cytochrome c release,
      and caspase-9 and -3 cleavage. This suggests that an intracellular stimulus
      initiates the observed apoptosis responses.

PMID- 20036024
TI  - Occurrence of psychrotolerant Bacillus cereus group strains in ice creams.
AB  - The occurrences of Bacillus cereus group strains in 40 ice cream samples were
      investigated. Among 109 isolated B. cereus group strains confirmed by 16S rDNA
      sequence analysis only 50 were identified as B. cereus and one as B.
      thuringiensis by using FDA (U.S. Food and Drug Administration) standard,
      indicating the two identification standards were highly inconsistent.
      Furthermore, the psychrotolerant growth properties and the occurrence of specific
      psychrotolerant genes of the isolates were also studied. Both psychrotolerant 16S
      rDNA fragments and enterotoxic genes could be detected among mesophilic and
      psychrotolerant strains. No relationship among psychrotolerance, presence of
      psychrotolerant 16S rDNA fragments and enterotoxic genes were found and the
      specific cspA fragment was only detected in a small fraction (9.5%) of the
      psychrotolerant isolates. One psychrotolerant isolate Bw2-1 was identified as B.
      weihenstephanensis, but no clear distinguishing characteristics between B.
      weihenstephanensis and psychrotolerant B. cereus were found. These results might
      be of importance for gaining further understanding of the growth properties of B.
      weihenstephanensis and psychrotolerant B. cereus as well as their contribution to
      food poisoning.

PMID- 20036025
TI  - Identification and expression analysis of the aldo-ketoreductase1-B10 gene in
      primary malignant liver tumours.
AB  - BACKGROUND & AIMS: The aim of our study was to search for highly up-regulated
      genes in primary malignant liver tumours and to analyse their expression at the
      mRNA- and protein level. METHODS: Using a random-based gene fishing approach
      (representational difference analysis coupled to array hybridisation) we
      identified 7 genes high abundantly expressed in hepatocellular carcinoma (HCC) as
      compared to non-neoplastic liver tissue, among them a gene fragment of the aldo
      ketoreductase (AKR) superfamily. Full length cloning and sequencing of the gene
      fragment identified it as B10 gene of the AKR-family 1 (AKR1B10). For expression
      analysis on transcriptional level quantitative real-time RT-PCR was performed in
      22 HCC and 22 non-neoplastic liver cirrhotic tissues. RESULTS: Our data
      demonstrate significantly higher expression levels of AKR1B10-mRNA in HCC
      compared to non-tumourous cirrhotic liver tissue (p<0.0001). To evaluate its
      protein expression in primary malignant liver tumours, we investigated tissue
      arrays of 210 HCC and 51 cholangiocarcinomas (CC) by immunohistochemistry, using
      a monoclonal antibody against AKR1B10. Protein staining of AKR1B10 was
      significantly increased in well and moderately differentiated tumours compared to
      corresponding non-neoplastic liver tissue (p=0.023). However, AKR1B10-staining
      decreased in advanced, low differentiated tumours with a significant inverse
      correlation between AKR1B10-staining and tumour proliferation, indicated by Ki67
      (MIB-1) staining (r=-0.89, p=0.02). CONCLUSION: The over-expression of AKR1B10 in
      early stages of well and moderately differentiated tumours and its down
      regulation in advanced tumour-stages with low grade of differentiation
      demonstrated that AKR1B10 may be a helpful marker for differentiation and
      proliferation of HCC and CC.

PMID- 20036026
TI  - A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer.
AB  - BACKGROUND & AIMS: Biliary tract cancer is highly lethal at presentation, with
      increasing mortality worldwide. Current diagnostic measures employing multiple
      criteria such as imaging, cytology, and serum tumor markers are not satisfactory,
      and a new diagnostic tool is needed. Because bile is a cognate metabolite-rich
      bio-fluid in the biliary ductal system, we tested a new metabolomic approach to
      develop an effective diagnostic tool. METHODS: Biles were collected prospectively
      from patients with cancer (n=17) or benign biliary tract diseases (n=21) with
      percutaneous or endoscopic methods. Nuclear magnetic resonance spectra (NMR) of
      these biles were analyzed using orthogonal partial least square discriminant
      analysis (OPLS-DA). RESULTS: The metabolomic 2-D score plot showed good
      separation between cancer and benign groups. The contributing NMR signals were
      analyzed using a statistical TOCSY approach. The diagnostic performance assessed
      by leave-one-out analysis exhibited 88% sensitivity and 81% specificity, better
      than the conventional markers (CEA, CA19-9, and bile cytology). CONCLUSION: The
      NMR-based metabolomics approach provides good performance in discriminating
      cancer and benign biliary duct diseases. The excellent predictability of the
      method suggests that it can, at least, augment the currently available diagnostic
      approaches.

PMID- 20036027
TI  - Recent issues in first-line treatment of advanced non-small-cell lung cancer:
      Results of an International Expert Panel Meeting of the Italian Association of
      Thoracic Oncology.
AB  - Platinum-based chemotherapy is the standard first-line treatment for patients
      with advanced non-small-cell lung cancer (NSCLC). However, randomized trials have
      recently demonstrated the efficacy of several new drugs (pemetrexed, bevacizumab,
      cetuximab, erlotinib, gefitinib) in this setting. Hence, the choice of optimal
      treatment is no longer limited to the different platinum-based doublets. In order
      to guide clinical management of patients with advanced NSCLC, assess the
      strengths and limitations of available evidence, and to suggest priorities for
      clinical research, the Italian Association of Thoracic Oncology organized an
      International Expert Panel Meeting on the first-line treatment of advanced NSCLC,
      which took place in Sperlonga (Italy) in May 2009. Experts recommended that every
      effort should be made to obtain adequate tumor tissue before initiating
      treatment. Tumor histology/cytology subtyping is now important for the correct
      choice of treatment. In particular, considering efficacy data obtained with
      pemetrexed and safety concerns with bevacizumab, a division between squamous and
      non-squamous tumors is necessary. Epidermal growth factor receptor (EGFR)
      mutation analysis, at present, is not recommended in all patients, but should be
      performed in subgroups of patients characterized by higher prevalence of
      sensitizing mutations (Asians, never smokers, women, adenocarcinoma). When a
      mutation is present, first-line treatment with single-agent EGFR tyrosine-kinase
      inhibitor may be considered. Finally, the potential benefit of maintenance
      treatment for patients without progression at the end of first-line should be
      carefully discussed with each patient. Although the number of treatment options
      for patients with advanced NSCLC has increased recently, their results remain
      modest and further research is mandatory.

PMID- 20036028
TI  - Effects of physical and geochemical heterogeneities on mineral transformation and
      biomass accumulation during biostimulation experiments at Rifle, Colorado.
AB  - Electron donor amendment for bioremediation often results in precipitation of
      secondary minerals and the growth of biomass, both of which can potentially
      change flow paths and the efficacy of bioremediation. Quantitative estimation of
      precipitate and biomass distribution has remained challenging, partly due to the
      intrinsic heterogeneities of natural porous media and the scarcity of field data.
      In this work, we examine the effects of physical and geochemical heterogeneities
      on the spatial distributions of mineral precipitates and biomass accumulated
      during a biostimulation field experiment near Rifle, Colorado. Field bromide
      breakthrough data were used to infer a heterogeneous distribution of hydraulic
      conductivity through inverse transport modeling, while the solid phase Fe(III)
      content was determined by assuming a negative correlation with hydraulic
      conductivity. Validated by field aqueous geochemical data, reactive transport
      modeling was used to explicitly keep track of the growth of the biomass and to
      estimate the spatial distribution of precipitates and biomass. The results show
      that the maximum mineral precipitation and biomass accumulation occurs in the
      vicinity of the injection wells, occupying up to 5.4vol.% of the pore space, and
      is dominated by reaction products of sulfate reduction. Accumulation near the
      injection wells is not strongly affected by heterogeneities present in the system
      due to the ubiquitous presence of sulfate in the groundwater. However,
      accumulation in the down-gradient regions is dominated by the iron-reducing
      reaction products, whose spatial patterns are strongly controlled by both
      physical and geochemical heterogeneities. Heterogeneities can lead to localized
      large accumulation of mineral precipitates and biomass, increasing the
      possibility of pore clogging. Although ignoring the heterogeneities of the system
      can lead to adequate prediction of the average behavior of sulfate-reducing
      related products, it can also lead to an overestimation of the overall
      accumulation of iron-reducing bacteria, as well as the rate and extent of iron
      reduction. Surprisingly, the model predicts that the total amount of uranium
      being reduced in the heterogeneous 2D system was similar to that in the 1D
      homogeneous system, suggesting that the overall uranium bioremediation efficacy
      may not be significantly affected by the heterogeneities of Fe(III) content in
      the down-gradient regions. Rather, the characteristics close to the vicinity of
      the injection wells might be crucial in determining the overall efficacy of
      uranium bioremediation. These findings have important implications not only for
      uranium bioremediation at the Rifle site and for bioremediation of other redox
      sensitive contaminants at sites with similar characteristics, but also for the
      development of optimal amendment delivery strategies in other settings.

PMID- 20036029
TI  - Mechanisms of cell behaviour in eukaryotes.

PMID- 20036030
TI  - The COP9 signalosome and its role in plant development.
AB  - The COP9 signalosome (CSN) is an evolutionarily conserved multiprotein complex
      with a role in the regulation of cullin-RING type E3 ubiquitin ligases (CRLs).
      CSN exerts its function on E3 ligases by deconjugating the ubiquitin-related
      protein NEDD8 from the CRL cullin subunit. Thereby, CSN has an impact on multiple
      CRL-dependent processes. In recent years, advances have been made in
      understanding the structural organisation and biochemical function of CSN:
      Crystal structure analysis and mass spectrometry-assisted studies have come up
      with first models of the pair-wise and complex interactions of the 8 CSN
      subunits. Based on the analysis of mutant phenotypes, it can now be taken as an
      accepted fact that--at least in plants--the major biochemical function of CSN
      resides in its deneddylation activity, which is mediated by CSN subunit 5 (CSN5).
      Furthermore, it could be demonstrated that CSN function and deneddylation are
      required but not essential for CRL-mediated processes, and models for the role of
      neddylation and deneddylation in controlling CRL activity are emerging.
      Significant advances have also been made in identifying pathways that are growth
      restricting in the Arabidopsis csn mutants. Recently it has been shown that a G2
      phase arrest, possibly due to genomic instability, restricts growth in
      Arabidopsis csn mutants. This review provides an update on recent advances in
      understanding CSN structure and function and summarises the current knowledge on
      its role in plant development and cell cycle progression.

PMID- 20036031
TI  - Homoglutathione synthetase and glutathione synthetase in drought-stressed cowpea
      leaves: expression patterns and accumulation of low-molecular-weight thiols.
AB  - Glutathione (GSH) is an abundant metabolite and a major antioxidant in plant
      cells. However, in the Leguminosae, homoglutathione (hGSH) may replace
      glutathione (GSH) partially or completely. To date, cowpea (Vigna unguiculata)
      has been considered a non-hGSH-producing species, and no hGSHS cDNA has been
      isolated. Here we report on the cloning of a full-length cDNA coding for a hGSHS
      (EC 6.3.2.23) and the cloning of a partial cDNA coding for a putative glutathione
      synthetase (GSHS; EC 6.3.2.3) in cowpea leaf extracts. These cDNAs possess,
      respectively, the leucine/proline hGSHS signature and the alanine/alanine GSHS
      signature at the 3' end. Expression analysis showed a significant up-regulation
      of hGSHS during progressive drought stress that could be directly related to the
      drought tolerance of the cowpea cultivar used, while GSHS was mainly
      constitutively expressed. Nevertheless, quantification of low-molecular-weight
      thiols confirmed the previous findings that cowpea is essentially a GSH producing
      plant, as no hGSH was detected in the leaves. These findings raise new questions
      regarding the function, activity and substrate specificity of the cloned hGSHS
      cDNA. These questions are discussed.

PMID- 20036032
TI  - Attrition from emergency medicine clinical practice in the United States.
AB  - STUDY OBJECTIVE: We estimate the annual attrition from emergency medicine
      clinical practice. METHODS: We performed a cross-sectional analysis of the
      American Medical Association's 2008 Physician Masterfile, which includes data on
      all physicians who have ever obtained a medical license in at least 1 US state.
      We restricted the analysis to physicians who completed emergency medicine
      residency training or who obtained emergency medicine board certification. We
      defined attrition as not being active in emergency medicine clinical practice.
      Attrition was reported as cumulative and annualized rates, with stratification by
      years since training graduation. Death rates were estimated from life tables for
      the US population. RESULTS: Of the 30,864 emergency medicine-trained or emergency
      medicine board-certified physicians, 26,826 (87%) remain active in emergency
      medicine clinical practice. Overall, type of attrition was 45% to non-emergency
      medicine clinical practice, 22% retired, 14% administration, and 10%
      research/teaching. Immediate attrition (<2 years since training graduation) was
      6.5%. The cumulative attrition rates from 2 to 15 years postgraduation were
      stable (5% to 9%) and thereafter were progressively higher, with 18% having left
      emergency medicine clinical practice at 20 years postgraduation and 25% at 30
      years postgraduation. Annualized attrition rates were highest for the first 5
      years postgraduation and after 40 years postgraduation; between 5 and 40 years,
      the rates remained low (<1%). The overall annual attrition rate from emergency
      medicine clinical practice, including estimated death rate, was approximately
      1.7%. CONCLUSION: Despite the high stress and demands of emergency medicine,
      overall attrition remains low and compares favorably with that of other medical
      specialties. These data have positive implications for the emergency physician
      workforce and are important for accurate estimation of and planning for emergency
      physician workforce needs.

PMID- 20036033
TI  - Biofilms in chronic suppurative otitis media and cholesteatoma: scanning electron
      microscopy findings.
AB  - BACKGROUND: Biofilms play a role in the pathogenesis of a variety of
      otorhinolaryngologic diseases, including otitis media and cholesteatoma. Despite
      this, relatively few studies have undertaken to demonstrate the presence of
      biofilms tissues from patients with chronic otitis media or infected
      cholesteatoma. OBJECTIVE/HYPOTHESIS: Our objective is to detect evidence of
      biofilms human chronic ear infections with scanning electron microscopy (SEM). We
      hypothesized that bacterial biofilms are present in patients with chronic otitis
      media. STUDY DESIGN: We performed prospective collection of tissue collected
      during middle ear surgery from 16 patients undergoing middle ear or mastoid
      surgery with chronic ear infections. METHODS: A total of 31 middle and mastoid
      tissue samples were harvested at the time of surgery and processed with critical
      point drying for SEM analysis. Samples were then searched for evidence of
      biofilms. RESULTS: Bacterial-shaped objects were identified that displayed both
      surface binding and the presence of a glycocalyx in 4 patients, findings
      consistent with bacterial biofilms. Most of these (3 of 4) were in patients with
      infected cholesteatoma, and biofims were identified in 60% of cholesteatoma cases
      (3 of 5). On the other hand, only 1 of 7 cases with chronic suppurative otitis
      media had evidence of biofilms. CONCLUSION: SEM supports the hypothesis that
      bacterial biofilms are common in chronic infections associated with cholesteatoma
      and are present in some cases of chronic suppurative otitis media without
      cholesteatoma.

PMID- 20036036
TI  - [Electrode position in elective electrical cardioversion of atrial fibrillation.
      A randomized study].
AB  - AIM: To compare the effectiveness of left anteroposterior (A-P) and apex-anterior
      (A-A) electrode position in the electrical cardioversion (ECV) of patients with
      atrial fibrillation (AF). DESIGN: Randomized clinical trial. LOCATION: ICU of a
      second-level hospital. PATIENTS AND METHODS: Ambulatory AF patients admitted to
      ICU for ECV with biphasic shocks. Up to a maximum of 3 shocks (150-200-200 J) are
      given in the electrode position determined by random numbers, and if sinus rhythm
      (SR) is not restored, electrode position is changed and 2 additional 200 J shocks
      are allowed. Both electrode positions are analyzed and compared to determine
      which one allows restoration of SR with the lowest number of shocks and least
      energy. RESULTS: Forty-six patients were included in the A-A group, and 45 in the
      A-P group. Sinus rhythm was restored in 92% of cases, although patients in the A
      A group needed a lower number of shocks and less energy: 1 versus 2 shocks
      (p=0,003) and 150 versus 350 J (p=0.017). Only one out of 5 patients in whom the
      A-A position had failed was reverted to RS with the A-P position, whereas 10 out
      of 13 patients in which A-P position had failed were reverted in the A-A position
      (p=0.038). CONCLUSIONS: The A-A position is more effective in the elective
      electrical cardioversion of atrial fibrillation, so we recommend this position as
      the first choice.

PMID- 20036035
TI  - Exploring the relationship between personality and regional brain volume in
      healthy aging.
AB  - Aging is characterized by a reduction in regional brain volumes, particularly in
      prefrontal and medial temporal regions. Recent evidence suggests that personality
      may be related to neuroanatomical integrity. The present investigation explored
      whether the three targeted personality traits of neuroticism, conscientiousness,
      and extraversion moderated cross-sectional age-related decline in measures of
      neural integrity. Estimates of the personality traits and volumes of cerebral
      gray and white matter, prefrontal and medial temporal regions were obtained in a
      sample of 79 healthy adults aged 44-88. Higher neuroticism was associated with
      smaller regional volumes and greater decreases in volume with increasing age.
      Higher conscientiousness was related to larger regional volumes and less decline
      with advancing age. These results suggest that personality may not only relate
      to, but may also moderate age-related cross-sectional decline in prefrontal and
      medial temporal regions.

PMID- 20036038
TI  - [Disparities in the effect of working conditions on health between immigrant and
      native-born populations in Spain].
AB  - OBJECTIVE: To examine the contribution of working conditions to permanent
      disability status in the immigrant and native-born populations in Spain by
      investigating the extent to which these two groups differ in terms of exposure to
      adverse working conditions and the impact of these conditions on disability
      status. METHODS: We used a dataset containing ample information on working lives
      and disability status and specified three probit models that estimated the
      following: 1) the extent to which working conditions affect the probability of
      suffering permanent disability, calculated separately for immigrants and natives;
      2) whether immigrants, in particular those from non-European Union-15 countries,
      have a higher probability of exposure to jobs with a greater rate of illness and
      injury risk; and 3) whether immigrants have a greater probability of being
      employed in jobs that concentrate three characteristics we consider to have
      adverse effects on health. RESULTS: Working conditions (such as illness and
      injury risk, lack of autonomy, and temporary jobs) have a significant impact on
      health in both groups, although the effect is higher for Spanish-born workers.
      Immigrants, particularly non-European Union immigrants, are more likely to be
      employed in jobs with adverse health conditions. CONCLUSIONS: Working conditions
      have a strong effect on health, similar to that of other variables, such as
      education. While immigrants are less likely to suffer disability than native-born
      workers, these differences are diluted the longer they stay in Spain. A labor
      market that relegates immigrants to the riskier jobs can be expected to translate
      into future health inequalities.

PMID- 20036034
TI  - A large-scale genetic association study to evaluate the contribution of Omi/HtrA2
      (PARK13) to Parkinson's disease.
AB  - High-profile studies have provided conflicting results regarding the involvement
      of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we
      performed a large-scale analysis of the association of common Omi/HtrA2 variants
      in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium. GEO-PD
      sites provided clinical and genetic data including affection status, gender,
      ethnicity, age at study, age at examination (all subjects); age at onset and
      family history of PD (patients). Genotyping was performed for the five most
      informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3 kb intervals
      (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as
      random effect models were used to provide summary risk estimates of Omi/HtrA2
      variants. The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No
      overall significant associations for the five Omi/HtrA2 SNPs and PD were observed
      using either fixed effect or random effect models. The summary odds ratios ranged
      between 0.98 and 1.08 and the estimates of between-study heterogeneity were not
      large (non-significant Q statistics for all 5 SNPs; I(2) estimates 0-28%). Trends
      for association were seen for participants of Scandinavian descent for rs2241028
      (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR
      1.17, p=0.02), but these would not be significant after adjusting for multiple
      comparisons and their Bayes factors were only modest. This largest association
      study performed to define the role of any gene in the pathogenesis of Parkinson's
      disease revealed no overall strong association of Omi/HtrA2 variants with PD in
      populations worldwide.

PMID- 20036040
TI  - Gas in the cavernous sinus-iatrogenic or pathological?

PMID- 20036039
TI  - Synthesis, in vitro antibacterial and antifungal evaluations of new alpha
      hydroxyphosphonate and new alpha-acetoxyphosphonate derivatives of tetrazolo [1,
      5-a] quinoline.
AB  - A series of new alpha-hydroxyphosphonate and alpha-acetoxyphosphonate derivatives
      have been synthesized for the first time of tetrazolo [1, 5-a] quinoline
      derivatives. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data
      elucidated the structures of the all newly synthesized compounds. In vitro
      antimicrobial activities of the synthesized compounds were investigated against
      Gram-positive Bacillus subtilis, Gram-negative Escherichia coli and fungi Candida
      albicans and Aspergillus niger. Some of the tested compounds showed significant
      antimicrobial activity.

PMID- 20036041
TI  - Metastatic cutaneous head and neck renal cell carcinoma with no known primary:
      case report.
AB  - Renal cell carcinoma represents 2-3% of all adult malignancies, and metastasis to
      the head and neck is a presenting complaint in 8% of these patients. Cutaneous
      facial renal cell carcinoma with no known primary renal tumour is unusual. We
      report a case of renal cell carcinoma of the nose with no known primary.

PMID- 20036042
TI  - Retrospective review of microsurgical repair of 222 lingual nerve injuries.
AB  - PURPOSE: Injury to the lingual nerve (LN) is a known complication associated with
      several oral and maxillofacial surgical procedures. We have reviewed the
      demographics, timing, and outcome of microsurgical repair of the LN. MATERIALS
      AND METHODS: A retrospective chart review was completed of all patients who had
      undergone microsurgical repair of the LN by one of us (R.A.M.) from March 1986
      through December 2005. A physical examination, including standardized
      neurosensory testing, was completed of each patient preoperatively. All patients
      were followed up periodically after surgery for at least 1 year, with
      neurosensory testing repeated at each visit. Sensory recovery was determined from
      the patient's final neurosensory testing results and evaluated using the
      guidelines established by the Medical Research Council Scale. The following data
      were collected and analyzed: patient age, gender, nerve injury etiology, chief
      sensory complaint (numbness or pain, or both), interval from injury to surgical
      intervention, intraoperative findings, surgical procedure, and neurosensory
      status at the final evaluation. The patients were classified according to whether
      they achieved "useful sensory recovery" or better, according to the Medical
      Research Council Scale, or had unsatisfactory or no improvement in sensation.
      Logistic regression methods and associated odds ratios (OR) were used to quantify
      the association between the risk factors and improvement. Receiver operating
      characteristic curve analysis was used to find the age threshold and duration
      that maximally separated the patient outcomes. RESULTS: A total of 222 patients
      (51 males and 171 females; average age 31.1 years, range 15 to 61) underwent LN
      repair and returned for at least 1 year of follow-up. The most common cause of LN
      injury was mandibular third molar removal (n = 191, 86%), followed by sagittal
      split mandibular ramus osteotomy (n = 14, 6.3%). Most patients complained
      preoperatively of numbness (n = 122, 55%) or numbness with pain (n = 94, 42.3%).
      The average interval from injury to surgery was 8.5 months (range 1.5 to 96). The
      most commonly performed operation was excision of a proximal stump neuroma with
      neurorrhaphy (n = 154, 69%), followed by external decompression with internal
      neurolysis (n = 29, 13%). Nineteen patients (8.6%) underwent an autogenous nerve
      graft procedure (greater auricular or sural nerve) for reconstruction of a nerve
      gap. A collagen cuff was placed around the repair site in 8 patients (3.6%;
      external decompression with internal neurolysis in 2 and neurorrhaphy in 6).
      Recovery from neurosensory dysfunction (defined by the Medical Research Council
      Scale as ranging from "useful sensory function" to a "complete return of
      sensation") was observed in 201 patients (90.5%; 146 patients with complete
      recovery and 55 patients with recovery to "useful sensory function"), and 21
      patients (9.5%) had no or inadequate improvement. Using the logistic regression
      model, a shorter interval between nerve injury and repair resulted in greater
      odds of improvement (OR 0.942, P = .0064); with each month that passed, the odds
      of improvement decreased by 5.8%. The receiver operating characteristic analysis
      revealed that patients who waited more than 9 months for repair were at a
      significantly greater risk of nonimprovement. Statistical significance was
      observed between patient age and outcome (OR 0.945, P = .0067) representing a
      5.5% decrease in the chance of recovery for every year of age in patients 45
      years old and older. The odds of a return of acceptable neurosensory function
      were better when the patient's presenting symptom was pain and not numbness (OR
      0.04, P < .001). CONCLUSIONS: Microsurgical repair of LN injury has the best
      chance of successful restoration of acceptable neurosensory function if done
      within 9 months of the injury. The likelihood of recovery after nerve repair
      decreased progressively when the repair occurred more than 9 months after injury
      and with increasing patient age.

PMID- 20036044
TI  - Straightforward management of a large pediatric scalp degloving injury in a
      combat zone.

PMID- 20036043
TI  - Reproducibility of 3 different tracing methods based on cone beam computed
      tomography in determining the anatomical position of the mandibular canal.
AB  - PURPOSE: To investigate the reproducibility of 3 different tracing methods to
      determine a reliable method to define the proper anatomical position of the
      mandibular canal based on cone beam computed tomography (CBCT) data. MATERIALS
      AND METHODS: Five dentate and 5 edentate patients were selected at random from
      the CBCT database. Two independent observers traced both the left and the right
      mandibular canal using 3-dimensional image-based planning software (Procera
      System NobelGuide; Nobel Biocare, Goteborg, Sweden). All mandibular canals were
      traced using 3 different methods. Method I was based on coronal views, also known
      as cross-sections. Panorama-like reconstructions were the starting point for
      method II. The third method combined methods I and II. RESULTS: With respect to
      interobserver reliability, no significant difference (P = .34) for the various
      methods was observed. The reproducibility was better in edentate than in dentate
      jaws (P = .0015). The difference between 2 tracings was the lowest for the
      combined method: within a range of 1.3 mm in 95% of the course of the canal. The
      most obvious deviations were mainly seen in the anterior part of the canal.
      CONCLUSIONS: The best reproducible method for mandibular canal tracing is the
      combined method III. Between observers, still a mean 95th percentile deviation
      threshold of 1.3 mm (SD 0.384) is noted, indicating that a safety zone of 1.7 mm
      should be respected. When planning surgery on CBCT-based data, surgeons should be
      aware of the obvious deviations located in the region of the anterior loop of the
      canal.

PMID- 20036045
TI  - Management protocol for anaphylaxis.
AB  - There is no universal agreement on the definition of anaphylaxis or the criteria
      for establishing its diagnosis, although it has been known to the field of
      emergency medicine for more than 100 years. Two meetings were convened by the
      National Institute of Allergy and Infectious Disease and Food Allergy and
      Anaphylaxis Network in April 2004 and July 2005. Representatives from 16
      different organizations and government bodies, including representatives from
      developed nations, continue working toward a universally accepted definition,
      criteria for diagnosis, and management of anaphylaxis. This article presents the
      latest concepts on anaphylaxis in the literature including the research needs in
      this area.

PMID- 20036046
TI  - Dominique-Jean Larrey: the effects of therapeutic hypothermia and the first
      ambulance.
AB  - The fields of emergency medicine and resuscitation are indebted to the Baron
      Dominique-Jean Larrey (1766-1842) for significant advances in patient care.
      Larrey was a great surgeon who served in the French army during Napoleon's rule.
      He developed one of the first ambulance services, utilized positive pressure
      ventilation, and introduced hypothermia as a form of therapy. He dedicated his
      professional life to improving the care of wounded soldiers on the battlefield.
      Larrey coined the term "Triage" to allocate resources to those most in need of
      emergent care. Today, many of his techniques still prevail in modern medicine.

PMID- 20036047
TI  - Capnography and chest-wall impedance algorithms for ventilation detection during
      cardiopulmonary resuscitation.
AB  - OBJECTIVE: Hyperventilation is both common and detrimental during cardiopulmonary
      resuscitation (CPR). Chest-wall impedance algorithms have been developed to
      detect ventilations during CPR. However, impedance signals are challenged by
      noise artifact from multiple sources, including chest compressions. Capnography
      has been proposed as an alternate method to measure ventilations. We sought to
      assess and compare the adequacy of these two approaches. METHODS: Continuous
      chest-wall impedance and capnography were recorded during consecutive in-hospital
      cardiac arrests. Algorithms utilizing each of these data sources were compared to
      a manually determined "gold standard" reference ventilation rate. In addition, a
      combination algorithm, which utilized the highest of the impedance or capnography
      values in any given minute, was similarly evaluated. RESULTS: Data were collected
      from 37 cardiac arrests, yielding 438min of data with continuous chest
      compressions and concurrent recording of impedance and capnography. The manually
      calculated mean ventilation rate was 13.3+/-4.3/min. In comparison, the
      defibrillator's impedance-based algorithm yielded an average rate of 11.3+/
      4.4/min (p=0.0001) while the capnography rate was 11.7+/-3.7/min (p=0.0009).
      There was no significant difference in sensitivity and positive predictive value
      between the two methods. The combination algorithm rate was 12.4+/-3.5/min
      (p=0.02), which yielded the highest fraction of minutes with respiratory rates
      within 2/min of the reference. The impedance signal was uninterpretable 19.5% of
      the time, compared with 9.7% for capnography. However, the signals were only
      simultaneously non-interpretable 0.8% of the time. CONCLUSIONS: Both the
      impedance and capnography-based algorithms underestimated the ventilation rate.
      Reliable ventilation rate determination may require a novel combination of
      multiple algorithms during resuscitation.

PMID- 20036048
TI  - Evaluation of transobturator tapes (E-TOT) study: randomised prospective single
      blinded study comparing inside-out vs. outside-in transobturator tapes in
      management of urodynamic stress incontinence: short term outcomes.
AB  - OBJECTIVES: To compare the "inside-out (TVT-O)" vs. "outside-in (ARIS)"
      transobturator tapes in the management of female urodynamic stress incontinence
      (USI) and to identify independent risk factors of failure of transobturator
      tapes. STUDY DESIGN: A prospective, single blinded, randomised trial. Women
      undergoing transobturator tapes as sole procedure in the period April 2005 and
      April 2007 were randomised to TVT-O for the inside-out approach and TOT-ARIS for
      the outside-in approach. The primary outcome measure at 6 months was the absence
      of USI on urodynamics. Secondary outcomes included; patient-reported success
      rates, overall patient satisfaction and peri-operative complications. RESULTS:
      341 women were recruited: 171 in the outside-in group and 170 in the inside-out.
      Severe post-operative thigh pain was twice as common in the inside-out group but
      this was not statistically significant (6.7% vs. 3.5%, p=0.19). 317 women
      completed the 6 months follow-up; objective cure rates and patient-reported
      success rates were 85.4 and 80.5%, respectively, with no significant difference
      between the groups (p=0.28 and p=0.138, respectively). On multivariate analysis:
      low maximum urethral closure pressure (MUCP) (<30 cm H2O) and previous
      incontinence surgery were confirmed as independent risk factors for objective
      failure of transobturator tape with increased odds of failure of 7.06 (2.85
      17.48) and 6.22 (2.34-16.52), respectively. CONCLUSION: This study shows no
      significant differences in the objective cure rates and patient-reported success
      rates between the "inside-out (TVT-O)" and "outside-in (ARIS)" transobturator
      tape procedures in the management of female USI at 6 months follow-up. Previous
      incontinence surgery and low MUCP were significant risk factors for failure of
      transobturator tapes.

PMID- 20036049
TI  - Low field intraoperative MRI-guided surgery of gliomas: a single center
      experience.
AB  - INTRODUCTION: The aim of this article is to report on our experience in using a
      low field intraoperative MRI (iMRI) system in glioma surgery and to summarize the
      hitherto use and benefits of iMRI in glioma surgery. PATIENTS AND METHODS:
      Between July 2004 and May 2009, a total of 103 patients harboring gliomas
      underwent tumor resection with the use of a mobile low field iMRI in our
      institution. Surgeries were performed as standard micro-neurosurgical procedures
      using regular instrumentarium. All patients underwent early postoperative high
      field MRI to determine the extent of resection. Adjuvant treatment was conducted
      according to histopathological grading and standard of care. RESULTS: All tumors
      could be reliably visualized on intraoperative imaging. Intraoperative imaging
      revealed residual tumor tissue in 51 patients (49.5%), leading to further tumor
      resection in 31 patients (30.1%). Extended resection did not translate into a
      higher rate of neurological deficits. When analyzing survival of patients with
      glioblastoma, patients undergoing complete tumor resection did significantly
      better than patients with residual tumor (50% survival rate at 57.8 weeks vs.
      33.8 weeks, log rank test p=0.003), while younger age did not influence survival
      (p=0.12). CONCLUSION: Low field iMRI is a helpful tool in modern neurosurgery and
      facilitates brain tumor resection to a maximum safe extent. Its use translates
      into a better prognosis for these patients with devastating tumors. Future
      studies covering the use of iMRI will need to be conducted in a prospective,
      randomized fashion to prove the true benefit of iMRI in glioma surgery.

PMID- 20036050
TI  - HMGB2 stabilizes p53 by interfering with E6/E6AP-mediated p53 degradation in
      human papillomavirus-positive HeLa cells.
AB  - We investigated the effect of HMGB2 on the stability of p53 protein in HeLa
      cells. Overexpression of HMGB2 led to accumulation of the p53 protein, whereas
      HMGB2 knockdown with siRNA resulted in a substantial decrease in the p53 protein
      level. The HMGB2-dependent increase of p53 stability was specific for HPV
      positive HeLa cells as HCT116 and MCF7 cell lines did not demonstrate this
      response. Co-expression of HMGB2 and HPV E6 prevented HPV E6 protein-mediated
      ubiquitination and degradation of p53. FACS analysis exhibited that HeLa cells
      transfected with HMGB2 displayed decreased cell proliferation, with a concomitant
      increase of the p53 protein and arrest of the cell cycle, predominantly in G1
      phase. Our findings collectively suggest that HMGB2 could stabilize p53 by
      interfering with E6/E6AP-mediated p53 degradation in HPV-positive HeLa cells.

PMID- 20036051
TI  - Anaerobic bio-removal of uranium (VI) and chromium (VI): comparison of microbial
      community structure.
AB  - Several microbial communities, obtained from uranium contaminated and non
      contaminated samples, were investigated for their ability to remove uranium (VI)
      and the cultures capable for this removal were further assessed on their
      efficiency for chromium (VI) removal. The highest efficiency for removal of both
      metals was observed on a consortium from a non-contaminated soil collected in
      Monchique thermal place, which was capable to remove 91% of 22 mg L(-1) U(VI) and
      99% of 13 mg L(-1) Cr(VI). This study revealed that uranium (VI) removing
      communities have also ability to remove chromium (VI), but when uranium (VI) was
      replaced by chromium (VI) several differences in the structure of all bacterial
      communities were observed. TGGE and phylogenetic analysis of 16S rRNA gene showed
      that the uranium (VI) removing bacterial consortia are mainly composed by members
      of Rhodocyclaceae family and Clostridium genus. On the other hand, bacteria from
      Enterobacteriaceae family were detected in the community with ability for
      chromium (VI) removal. The existence of members of Enterobacteriaceae and
      Rhodocyclaceae families never reported as chromium or uranium removing bacteria,
      respectively, is also a relevant finding, encouraging the exploitation of
      microorganisms with new abilities that can be useful for bioremediation.

PMID- 20036052
TI  - Removal of Malachite Green from aqueous solution using degreased coffee bean.
AB  - This study reports on the feasibility of employing degreased coffee beans (DCB)
      as adsorbent for Malachite Green (MG) removal in dyeing wastewater. The iodine
      value (IV), specific surface area (SSA) and porosity of the raw coffee beans
      (RCB) used in the study increased after the degreasing process, resulting in
      significant increase in the adsorption of MG onto DCB. Employing a batch
      experimental set-up, optimum conditions for complete color removal and adsorption
      of MG by DCB was studied considering parameters such as effect of degreasing
      process, adsorbent dosage, initial dye concentration, reaction temperature and
      pH. Adsorbed amount of MG by DCB increased with increasing DCB dosage and initial
      MG concentration. The rate of the adsorption reaction followed the pseudo second
      order kinetics with the sorption isotherm well fitted to the Freundlich and the
      Langmuir isotherm models. Thermodynamic studies revealed that the adsorption
      processes is spontaneous and endothermic in nature. DCB has potentials for
      application as adsorbent for the removal of MG from dyeing process wastewater.

PMID- 20036053
TI  - Sequestration of carbon dioxide (CO2) using red mud.
AB  - Red mud, an aluminium industry hazardous waste, has been reported to be an
      inexpensive and effective adsorbent. In the present work applicability of red mud
      for the sequestration of green house gases with reference to carbon dioxide has
      been studied. Red mud sample was separated into three different size fractions
      (RM I, RM II, RM III) of varying densities (1.5-2.2 g cm(-3)). Carbonation of
      each fraction of red mud was carried out separately at room temperature using a
      stainless steel reaction chamber at a fixed pressure of 3.5 bar. Effects of
      reaction time (0.5-12 h) and liquid to solid ratio (0.2-0.6) were studied for
      carbonation of red mud. Different instrumental techniques such as X-ray
      diffraction, FTIR and scanning electron microscope (SEM) were used to ascertain
      the different mineral phases before and after carbonation of each fraction of red
      mud. Characterization studies revealed the presence of boehmite, cancrinite,
      chantalite, hematite, gibbsite, anatase, rutile and quartz. Calcium bearing
      mineral phases (cancrinite and chantalite) were found responsible for carbonation
      of red mud. Maximum carbonation was observed for the fraction RM II having higher
      concentration of cancrinite. The carbonation capacity is evaluated to be 5.3 g of
      CO(2)/100 g of RM II.

PMID- 20036054
TI  - Olive mill wastewater evaporation management using PCA method Case study of
      natural degradation in stabilization ponds (Sfax, Tunisia).
AB  - Olive mill wastewater (OMW) evaporation ponds management was investigated in five
      serial evaporation open-air multiponds of 50 ha located in Sfax (Tunisia).
      Physico-chemical parameters and microbial flora evolution were considered.
      Empirical models describing the OMW characteristic changes with the operation
      time were established and Principal Component Analysis (PCA) described the
      correlation between physico-chemical and biological parameters. COD, BOD, total
      solids, polyphenols and electrical conductivity exhibited first-order models.
      Four groups exhibited high correlations. The first included temperature, density,
      COD, TSS, TS, BOD, VS, TOC, TKN, polyphenols and minerals. The second group was
      made up of yeasts and moulds. The third group was established with phenolic
      compounds, total sugars, fats, total phosphorous, NH(4)(+) and pH. The fourth
      group was constituted by exclusively aerobic bacteria. Bacterial-growth toxic
      effect was exhibited by high organic load, ash content and polyphenols, whereas
      moulds and yeasts were more adapted to OMW. During the storage, all the third
      group parameter values decreased and were inversely related to the others. In the
      last pond, COD, BOD, TS and TSS rates were reduced by 40%, 50%, 50% and 75%
      respectively. The evaporation and the biological activity were the main processes
      acting, predicting the OMW behavior during evaporation in air-open ponds.

PMID- 20036055
TI  - Desorption behavior of methylene blue on pyromellitic dianhydride modified
      biosorbent by a novel eluent: acid TiO2 hydrosol.
AB  - In this study, waste beer yeast powder was modified by pyromellitic dianhydride
      to improve its adsorption capacities for cationic dye: methylene blue (MB).
      According to the Langmuir equation, the maximum uptake capacities (q(m)) of the
      modified biomass for MB was 830.8 mg g(-1), which was about five times than that
      obtained on the unmodified biomass. Adsorption mechanism was investigated by
      FTIR. Desorption kinetics of methylene blue in six solvents: HCl (0.1 mol L(-1)),
      ethanol, mixtures of HCl (0.1 mol L(-1)) and ethanol with different volume ratio
      and a self-clean eluent: acid TiO(2) were studied in details. Results showed that
      desorption kinetics curve fit the two-step kinetic model, and methylene blue
      release process was distinctly divided into two steps: rapid and slow desorption
      steps. 52.2% of the methylene blue could be desorbed into TiO(2) hydrosol after
      30 h desorption at the first desorption cycle, and the desorbed dye in TiO(2)
      hydrosol could be degrade completely under sunlight irradiation. After three
      desorption-photodegradation cycles, 80.0% of the absorbed dyes could be desorbed
      from the surface of the modified biomass. Although there was much work to do, the
      self-clean eluent: TiO(2) hydrosol had great potential in practical use.

PMID- 20036056
TI  - Nociceptin/Orphanin FQ in PAG modulates the release of amino acids, serotonin and
      norepinephrine in the rostral ventromedial medulla and spinal cord in rats.
AB  - High density Nociceptin/Orphanin FQ (N/OFQ) and its receptor (NOPr) have been
      found in the ventrolateral periaqueductal gray (vlPAG), a main output pathway
      involved in the descending pain-control system. Our previous study demonstrated
      that the microinjection of N/OFQ into the vlPAG markedly facilitated nociceptive
      responses of spinal dorsal horn neurons. The aim of the present work was to
      further provide evidence for the supraspinal mechanisms of action for N/OFQ
      mediated nociceptive facilitation by examining the effect of N/OFQ in the vlPAG
      on neurotransmitter release in the descending pain-control system, including the
      nucleus raphe magnus (NRM), nucleus reticularis gigantocellularis (NGC) and
      dorsal horn of the spinal cord. The results showed that the microinjection of
      N/OFQ into the vlPAG produced robust decreases in 5-hydroxytryptamine (5-HT,
      serotonin), norepinephrine (NE), and gamma-aminobutyric acid (GABA), and increase
      in glutamate (Glu) release in the spinal dorsal horn. Spinal application of 5-HT,
      2-Me-5-HT (5-HT(3) receptor agonist), muscimol (GABA(A) receptor agonist), and
      baclofen (GABA(B) receptor agonist) significantly blocked intra-vlPAG-induced
      facilitation on nociceptive responses. However, the extracellular concentrations
      of these neurotransmitters in the NRM and NGC exhibited diversity following intra
      vlPAG of N/OFQ. In the NRM, intra-vlPAG injection of N/OFQ significantly
      decreased 5-HT, NE, and Glu, but increased GABA release. Differently, in the NGC,
      both NE and GABA releases were attenuated by intra-vlPAG of N/OFQ, whereas the
      concentration of 5-HT and Glu exhibited a trend to increase. These findings
      provide direct support for the hypothesis that intra-PAG of N/OFQ-induced
      facilitation of nociceptive responses is associated with the release of 5-HT, NE,
      and amino acids.

PMID- 20036058
TI  - Acute phase protein response in Alpine ibex with sarcoptic mange.
AB  - The acute phase proteins (APP) are a group of serum proteins that change their
      concentration in animals following external or internal challenges, such as
      infection, inflammation or stress. The concentrations of four APPs, including
      serum amyloid A (SAA), haptoglobin (Hp), alpha(1)-acid glycoprotein (AGP) and
      ceruloplasmin (Cp) were determined in serum collected from healthy Alpine ibexes
      (Capra ibex) and ibexes with Sarcoptes scabiei mange. Primary structures of all
      four APPs were determined by cDNA sequencing. The concentrations of all four APPs
      were higher in serum of animals with clinical signs of sarcoptic mange when
      compared to healthy animals. Two of the APPs, including SAA and AGP, acted as
      major APPs, since their serum concentrations were increased more than 10-folds
      when compared to healthy animals (P<0.001). The other two APPs, including Hp and
      Cp, acted as minor acute phase proteins, as their concentrations were increased
      from two to five folds (P<0.001). These findings provide a remarkable potential
      as diagnostic markers for the early detection of sarcoptic mange in free ranging
      animals.

PMID- 20036059
TI  - Viability of the nematophagous fungus Pochonia chlamydosporia after passage
      through the gastrointestinal tract of horses.
AB  - The predatory capacity of the nematophagous fungus Pochonia chlamydosporia
      (isolate VC4) embedded in sodium alginate pellets after passage through the
      gastrointestinal tract of horses was assessed in vitro against Oxyuris equi eggs.
      Twelve previously dewormed crossbred mares, average weight of 362.5kg (+/-21)
      were used in the experiment. Each animal of the treated group received an oral
      dose (100g) of sodium alginate pellets containing P. chlamydosporia mycelial
      mass. The control group received pellets without fungus. Faecal samples from
      fungus-treated and control groups were collected at intervals of 8, 12, 24, 36,
      48 and 72h after pellet administration and placed in Petri dishes containing 2%
      water-agar. One thousand eggs of O. equi were plated in Petri dishes of both
      treated and control groups, with six replicates, and incubated in oven, 25
      degrees C, in the dark, for 30 days. At the end of the experiment, one hundred
      eggs were removed from each Petri dish and classified according to the following
      parameters: type 1, physiological and biochemical effect without morphological
      damage to eggshell, with hyphae adhered to the shell; type 2, lytic effect with
      morphological change in the eggshell and embryo without hyphal penetration, and
      type 3, lytic effect with morphological change in the eggshell and embryo, with
      hyphal penetration and internal egg colonization. Chlamydospore production was
      observed in Petri dishes of the treated group. The isolate VC4 remained viable
      after passing through the gastrointestinal tract of horses and maintained the
      ovicidal activity against O. equi eggs when compared with the control group
      (p<0.01) after each collection interval: 29.1% (8h), 28.2% (12h), 31.1% (24h),
      27.4% (36h), 30.9% (48h) and 28.4% (72h). The results suggest that P.
      chlamydosporia could be used as an effective biological control agent of O. equi
      eggs in natural conditions.

PMID- 20036060
TI  - Improved Cryptosporidium parvum oocyst propagation using dexamethasone suppressed
      CF-1 mice.
AB  - This study evaluates Cryptosporidium parvum oocyst production in dexamethasone
      suppressed CF-1 and C57BL/6 mice. Both models can yield 1 x 10(9) total oocysts
      over a 20-day production period; however, only 20 CF-1 mice are required to
      reliably achieve this goal compared to 40 C57BL/6 mice. Although oocyst yields
      per mouse are similar for both mouse strains, the survival rate for CF-1 mice is
      higher, resulting in reduced lost production time per study when compared to the
      C57BL/6 mice. This study presents a more efficient and cost effective
      dexamethasone suppressed murine model of propagating high concentrations of C.
      parvum oocysts.

PMID- 20036061
TI  - Securing the airway in a child with extensive post-burn contracture of the neck:
      a novel strategy.

PMID- 20036063
TI  - A new surgical technique for stabilizing toes in plantar flexion positions after
      solution of dorsum scar.

PMID- 20036064
TI  - Toxic shock syndrome toxin-1 (TSST-1) antibody levels in Japanese children.
AB  - Children with burns have a greater risk of developing toxic shock syndrome (TSS)
      than adults. This risk is thought to be associated with colonisation by toxic
      shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus in children with
      insufficient antibody titers. The diagnosis of TSS is difficult because, in the
      early stages, its signs and symptoms resemble those of other common childhood
      illnesses such as scarlet fever. If the condition is not treated promptly, the
      mortality rate is high. This study was designed to determine the titers of TSST-1
      serum antibody in Japanese children, in order to prevent TSS and facilitate its
      early diagnosis. Between May 2006 and May 2007, we studied 119 patients who were
      treated in the Department of Plastic and Reconstructive Surgery of Kanazawa
      Medical University Hospital. An enzyme-linked immunosorbent assay (ELISA) was
      used to test the level of the IgG antibody to TSST-1 in the patients' serum
      samples. The percentage of cases testing for TSST-1 antibody in the patients
      under 6 months old was 78.6%, and it was lowest (21.3%) in the age group from 6
      to 12 months old. The group of patients older than 41 years showed the highest
      rate of positivity (100.0%) for TSST-1 antibody. Higher titers of TSST-1 antibody
      were found within the first 6 months after birth, and lower titers were found
      between 6 months and 2 years old. The titers began to increase again after age
      three. The high morbidity of TSS in children around 2 years of age was proven to
      be related to changes in the titers of TSST-1 antibody. Infants under 6 months
      old are protected from TSS because of the high level of TSST-1 antibody they
      receive from their mother. Children are at risk of developing staphylococcal
      toxic shock syndrome when their immune system is immature and they have no
      protective circulating anti-TSS antibodies.

PMID- 20036065
TI  - Three cases of inner ear damage after electrical burns.

PMID- 20036067
TI  - Gore-tex bags versus traditional hand bandaging: a comparison of range of motion,
      sensation and function in healthy subjects.
AB  - INTRODUCTION: Little evidence exists evaluating the possible effect of dressings
      on the recovery of function, sensation and joint motion following a hand burn.
      Hand burns are traditionally covered by a layer of non-adherent dressing followed
      by gauze and bandages. However, there is no evidence for the efficacy of this
      type of coverage relative to a functional recovery. The Gore-tex bag has a small
      body of research supporting its ability to provide a superior healing atmosphere,
      however there is no literature directly comparing it with the traditional
      dressing. METHOD: A randomised cross-over design was implemented to compare Gore
      tex bags and traditional dressings in 30 healthy volunteers. Seven outcome
      measures of function, sensation, joint range of movement and subject perceptions
      were recorded before dressing, during both Gore-tex and traditional dressing
      interventions and between dressings. RESULTS: Statistically significant
      differences were found between the traditional dressings and Gore-tex bags. The
      Gore-tex bag dressings proved better for digit range of motion, 1st CMC joint
      motion and sensation. The traditional dressings were significantly better when
      perceived comfort was tested and there was no significant difference between the
      traditional dressing and Gore-tex bag regarding function and perceived function.
      CONCLUSION: The results of this study suggest that traditional dressings may
      detrimentally affect movement and reduce sensation but not necessarily affect
      function or comfort. Further investigation in a patient cohort with burnt hands
      is recommended.

PMID- 20036068
TI  - The use of Japanese "kenzan" flower holders to create scar-less drainage holes in
      skin grafts.

PMID- 20036069
TI  - A retrospective case series study of Deepavali fire walkers in Singapore.

PMID- 20036070
TI  - Adult respiratory distress syndrome or congestive heart failure in severe burn: a
      role for brain natriuretic peptide.

PMID- 20036072
TI  - Trauma exposure in relation to basal salivary cortisol and the hormone response
      to the dexamethasone/CRH test in male railway employees without lifetime
      psychopathology.
AB  - BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA)-axis is
      hypothesized to underlie stress-related psychiatric disorders such as post
      traumatic stress disorder (PTSD). We aimed to explore whether trauma exposure is
      associated with alterations in HPA-axis functioning in the absence of lifetime
      psychiatric morbidity. METHOD: We included 39 trauma-exposed healthy male
      subjects (mean age=47 years; SD=9.2) and 24 non-exposed healthy male controls
      (mean age=47.4 years; SD=14.5). All subjects were free of lifetime
      psychopathology. Basal salivary cortisol levels (on two consecutive days) as well
      as the cortisol and adrenocorticotropic hormone (ACTH) response to the combined
      dexamethasone/corticotropin releasing hormone (Dex/CRH) challenge test were
      analyzed using general linear models (GLM) adjusted for body mass index, age and
      smoking status. RESULTS: A blunted salivary cortisol awakening response was found
      in the exposed group compared to the non-exposed group (F(1,57)=5.46, p=.02).
      Consistent with these findings, salivary diurnal cortisol was lower in the trauma
      exposed versus non-exposed group (F(1,57)=4.04, p=.05). No differences, however,
      were found between both groups for plasma cortisol or ACTH responses to the
      Dex/CRH test. CONCLUSION: Low basal cortisol levels were found in trauma-exposed
      men, suggesting that HPA-axis alterations in men are associated with trauma
      exposure during adulthood, also in the absence of psychopathology.

PMID- 20036074
TI  - The main product of specialized tissues regulates cell life and may cause
      neoplastic transformation.
AB  - Many tissues and cells in vertebrates are highly specialized and devoted to a
      single function through the action of a single molecule, that we call the "main
      product" (MP) of the cell. The hypothesis here proposed is that these MPs control
      all aspects of the cell life, namely activity, division, differentiation and
      apoptosis. Evidences supporting this hypothesis are reported for the immune
      system, pancreatic beta-cells, melanocytes, connective tissues, thyroid cells,
      skin and erythroid cells. In all cases cell division and differentiation is
      promoted by a normal activity of the MP, while hyperactivity leads to cell
      apoptosis. Evidences are also provided that alterations of the activity of the MP
      may elicit pathological disorders; in particular mutations altering the structure
      of the MP may elicit tumoural transformation.

PMID- 20036073
TI  - Activation of central CRF receptor 1 by cortagine results in enhanced passive
      coping with a naturalistic threat in mice.
AB  - CRF receptor subtype 1 (CRF1), abundantly expressed in the central nervous
      system, has been implicated in defensive behavior in rodents. Pharmacological
      activation of CRF1 by peptidic agonists results in enhancement of anxiety-like
      behavior. However, receptor specificity of commonly used agonists was confounded
      by significant affinity to other receptors and widely used laboratory tests of
      experimental anxiety suffer from artificial aversive stimulation (e.g. electric
      shock), and limited measures of anxiety-like behavior. We used the recently
      developed, CRF1-selective agonist cortagine in a mouse model of defensive
      behaviors under semi-natural conditions, the rat exposure test (RET). Cortagine
      was injected bilaterally into the cerebral ventricles (i.c.v.) of male C57Bl/6J
      mice, 20min before exposure to a rat in specifically designed box that evokes a
      wide variety of defensive behaviors such as active/passive avoidance, freezing,
      risk assessment, and burying. Pre-injection of the CRF receptor antagonist acidic
      astressin was used to test for receptor specificity of the observed cortagine
      effects. A control experiment with no rat present was performed to test for
      baseline effects of cortagine in the exposure setup. Cortagine dose-dependently
      enhanced passive avoidance and freezing while burying was decreased. CRF receptor
      antagonism reliably blocked the effects of cortagine. Our results confirm
      previous findings of anxiogenic-like effects of cortagine, and demonstrate the
      usefulness of the RET in investigating differential pattering of drug-induced
      anxiety-like behavior in mice. In conclusion, our results suggest that CRF1
      activation in forebrain areas promotes passive coping with the natural threat
      presented in the RET.

PMID- 20036075
TI  - A critique of recent hypotheses on oral (and lung) cancer induced by water pipe
      (hookah, shisha, narghile) tobacco smoking.
AB  - The medical hypothesis that the mainstream smoke (the one inhaled by the user)
      from "water pipes" (mainly: shisha, hookah, narghile) causes oral cancer is
      certainly acceptable. However, most of the recent reviews on this issue,
      including an attempt to develop an hypothesis for hookah carcinogenesis, have not
      cited key references of the world available literature which, so far, generally
      do not support such an hypothesis. Besides, the proposal is biased since it is
      apparently an adaptation of the cigarette model whereas cigarette and hookah
      smokes are, chemically to start with, completely different. Furthermore, all
      water pipes, despite their striking varieties and the consequences on the
      chemical processes, are, according to the same cancer-hypothesis, considered as
      one. The reason is the use, in the cited mainstream literature, of a nominalism
      ("waterpipe", often in one word) which does not allow any distinction between
      devices. This critical article suggests to take into account all the peculiar
      characteristics into consideration in order to come up with another (or several
      other) carcinogenesis model(s). "Firmly believ[ing] that water pipe smoking can
      provoke lung cancer as well as oral cancer", based on what may be seen as a
      rather reductionist view of the issue, is not enough.

PMID- 20036076
TI  - Sleep position and shoulder pain.
AB  - The overuse theory for musculoskeletal joint pain cannot explain adequately the
      occurrence of shoulder pain in those who do not engage in activities that involve
      repeated and stressful use of the shoulder since the percentage of the painful
      right shoulders usually does not match the percentage of dominant right arms in
      such individuals. An alternative hypothesis is presented to propose that shoulder
      pain is caused by postural immobility in the decubitus or side position during
      sleep. Prolonged pressure on the shoulder caused by the weight of the thorax can
      produce enough damage to cause subsequent shoulder pain. In order to test this
      hypothesis, a preliminary study was carried out to compare the laterality of
      shoulder pain with the laterality of sleep position. The calculated laterality
      ratios for sleep position and shoulder pain were found to be strikingly similar,
      suggesting a causal relationship between the two phenomena. However, the
      prevalence of shoulder pain in the general population was found to be smaller
      than the percentage of the time people would spend sleeping in the decubitus
      position. This discrepancy could be explained by the idea that in order for
      shoulder pain to develop subjects may have to spend longer times in the same
      decubitus position before changing to another position than the average person
      would. Additional evidence from published clinical studies also supports the
      postural theory of shoulder pain. More studies can be done to test this
      hypothesis by focusing on the sleep habits of patients with shoulder pain.
      According to the present hypothesis shoulder pain should for the most part occur
      on the side that the patient preferred to sleep on before the onset of shoulder
      pain. The postural theory of shoulder pain provides the possibility for a new and
      noninvasive method to treat shoulder pain by the modification of posture during
      sleep.

PMID- 20036077
TI  - Identification of Anaplasma centrale major surface protein-2 pseudogenes.
AB  - The present study was aimed to identify msp2 pseudogenes and MSP2 variants in the
      vaccine Anaplama centrale strain. Five msp2 pseudogenes were identified in the A.
      centrale genome, and multiple MSP2 variants that emerged during both acute and
      persistent infection were detected. The pseudogene copies of msp2 were truncated;
      they contained a central hypervariable region flanked by short portions of the 5'
      and 3' conserved regions. Alignment of the hypervariable region sequence of the
      expression site of MSP2 variants with msp2 pseudogenes showed that MSP2 variants
      are generated by two mechanisms, previously described in Anaplasma marginale: (i)
      recombination of the whole pseudogene into the single msp2 expression site, and
      (ii) recombination of small segments of pseudogenes into the expression site by
      segmental gene conversion. The present study showed that the A. centrale MSP2
      variants and the msp2 pseudogene repertoire were different from those reported
      for A. marginale. Unique MSP2 variants and pseudogenes identified in the vaccine
      strain allow the A. centrale-vaccinated cattle to be superinfected with the field
      strains of A. marginale. The knowledge gained in the present study on the
      mechanisms of antigenic variations in the vaccine strain of A. centrale is a
      further step in the development of a new generation vaccine against anaplasmosis.

PMID- 20036078
TI  - Genotyping of bovine viral diarrhea viruses from cattle in China between 2005 and
      2008.
AB  - Eighteen bovine viral diarrhea viruses (BVDV) from cattle in China between 2005
      and 2008 were genetically typed by sequencing of the 5'-untranslated region (5'
      UTR) of the viral genome and for selected isolates the N(pro) region.
      Phylogenetic reconstructions indicated that all of the 18 BVDV positive samples
      examined in this work clustered within the BVDV type 1 genotype. Of the 15
      previously described subgenotypes of BVDV1 (1a-1o), 12 of the samples examined in
      this work clustered with the Chinese BVDV ZM-95 strain of pig origin, which was
      the prototype of BVDV1m, while 2 samples clustered with the BVDV1b. But 4 samples
      formed a separate group appearing to be a potentially new subgenotype, which was
      tentatively typed as "BVDV1p". Based on these results there appears to be highly
      genetic variation within the Chinese BVDV field isolates. As well, the
      phylogenetic reconstructions indicate that the clustering of the Chinese BVDV1m
      subgenotype in the phylogenetic tree is a result of geographic isolation. The
      information obtained from this work will be useful when carrying out
      epidemiological surveys of BVDV detected in China, especially for the BVDV1m
      detection in Chinese cattle.

PMID- 20036079
TI  - Estimation of the sensitivity of four sampling methods for Mycoplasma
      hyopneumoniae detection in live pigs using a Bayesian approach.
AB  - Four sampling techniques for Mycoplasma hyopneumoniae detection, namely nasal
      swabbing, oral-pharyngeal brushing, tracheo-bronchial swabbing and tracheo
      bronchial washing, were compared in naturally infected live pigs. In addition, a
      quantitative real-time PCR assay for M. hyopneumoniae quantification was
      validated with the same samples. 60 finishing pigs were randomly selected from a
      batch of contemporary pigs on a farm chronically affected by respiratory
      disorders. Each pig was submitted to nasal swabbing, oral-pharyngeal brushing,
      tracheo-bronchial swabbing and tracheo-bronchial washing. Nested-PCR and real
      time PCR assays were performed on all samples. A Bayesian approach was used to
      analyze the nested-PCR results of the four sampling methods (i.e. positive or
      negative) to estimate the sensitivity and specificity of each method. M.
      hyopneumoniae was detected by nested-PCR in at least one sample from 70% of the
      pigs. The most sensitive sampling methods for detecting M. hyopneumoniae in live
      naturally infected pigs were tracheo-bronchial swabbing and tracheo-bronchial
      washing, as compared to oral-pharyngeal brushing and nasal swabbing. Swabbing the
      nasal cavities appeared to be the least sensitive method. Significantly higher
      amounts of M. hyopneumoniae DNA were found at the sites of tracheo-bronchial
      sampling than in the nasal cavities or at the oral-pharyngeal site (p<0.001).
      There was no difference between the tracheo-bronchial washing and the tracheo
      bronchial swabbing results (p>0.05). Our study indicated that tracheo-bronchial
      swabbing associated with real-time PCR could be an accurate diagnostic tool for
      assessing infection dynamics in pig herds.

PMID- 20036080
TI  - The diagnosis of proventricular dilatation disease: use of a Western blot assay
      to detect antibodies against avian Borna virus.
AB  - Avian Borna virus (ABV) has recently been shown to be the causal agent of
      proventricular dilatation disease (PDD) a lethal neurologic disease of captive
      psittacines and other birds. An immunoblot assay was used to detect the presence
      of antibodies against avian Borna virus in the serum of affected birds. A lysate
      from ABV-infected duck embryo fibroblasts served as a source of antigen. The
      assay was used to test for the presence of antibodies to ABV in 117 birds. Thirty
      of these birds had biopsy or necropsy-confirmed proventricular dilatation disease
      (PDD), while the remaining 87 birds were apparently healthy or were suffering
      from diseases other than PDD. Sera from 27 of the 30 PDD cases (90%) contained
      antibodies to ABV. Seventy-three (84%) of the apparently "healthy" birds were
      seronegative. Additionally, sera from seven macaws and one parrot trapped in the
      Peruvian Amazon were seronegative. Positive sera recognized the bornaviral
      nucleoprotein (N-protein). While the presence of antibodies to ABV largely
      corresponded with the development of clinical PDD, 14 apparently healthy normal
      birds possessed detectable antibodies to ABV. The existence of a carrier state
      was confirmed when 13 of 15 apparently healthy cockatiels were shown by PCR to
      have detectable ABV RNA in their feces. Western blot assays may be of significant
      assistance in diagnosing proventricular dilatation disease. Many apparently
      healthy birds may however be seronegative while, at the same time, shedding ABV
      in their feces.

PMID- 20036081
TI  - Detection of spatial and temporal spread of Mycobacterium avium subsp.
      paratuberculosis in the environment of a cattle farm through bio-aerosols.
AB  - Environmental samples were collected to investigate the spatial and temporal
      spread of Mycobacterium avium subsp. paratuberculosis (MAP) in a dairy cattle
      barn before and after the introduction of two groups of MAP-shedding animals.
      Samples collected off the floor of the barn reflected the moment of sampling
      whereas samples collected by microfiber wipes at a minimal of 3m height contained
      the accumulated settled dust over a 3-week period. Samples were analysed by IS900
      qPCR for the presence of MAP DNA and by culture for viable MAP bacteria. MAP DNA
      was detected in a large number of sites both before and after introduction
      cattle. MAP DNA was detected inside the barn in floor and dust samples from
      cubicles and slatted floors and in settled dust samples located above the slatted
      floors and in the ventilation ridge opening. Outside the barn MAP DNA was
      detected by PCR in samples reflecting the walking path of the farmer despite
      hygiene measures. No viable MAP was detected before the introduction of shedder
      cattle. Three weeks later viable MAP was found inside the barn at 7/49 locations
      but not outside. Fifteen weeks later viable MAP was also detected in
      environmental samples outside the barn. In conclusion, introduction of MAP
      shedding cattle lead to widespread contamination of the internal and external
      environment of a dairy barn, including the presence of viable MAP in settled dust
      particles suggesting potential transmission of MAP infection through bio
      aerosols.

PMID- 20036082
TI  - Effects of rhynchophylline and isorhynchophylline on nitric oxide and endothelin
      1 secretion from RIMECs induced by Listeriolysin O in vitro.
AB  - To investigate the effects of Listeriolysin O (LLO) on morphology, nitric oxide
      (NO) and endothelin-1 (ET-1) release by rat intestinal microvascular endothelial
      cells (RIMECs). We aimed to elucidate a preliminary therapeutic mechanism of
      action of rhynchophylline and isorhynchophylline (active components of Uncaria
      rhynchophylla) on listeriosis treatment and how they regulate the LLO-induced
      parasecretion of vasoactive agents in RIMECs. A RIMECs injury model was
      established by stimulating the cells with different concentrations of LLO.
      Compared with NC, LLO stimulation caused a dose-dependent decrease in RIMECs
      viability. After 12h, the levels of secreted NO and ET-1 were higher than NC and
      the ratio of NO:ET-1 decreased. The mRNA expression results of iNOS and ET-1 mRNA
      show the same trend. These deleterious effects could be partially reversed by the
      addition of rhynchophylline and isorhynchophylline at the same time as LLO. By
      preventing the morphological changes, decreasing cell death, and preventing
      disordered NO and ET-1 production in RIMECs induced by LLO, rhynchophylline and
      isorhynchophylline may help improve therapy for listeriosis.

PMID- 20036083
TI  - A survey of Western Australian sheep, cattle and kangaroos to determine the
      prevalence of Coxiella burnetii.
AB  - The objective of this study was to investigate the prevalence of Coxiella
      burnetii in two domestic ruminant species (cattle and sheep) and the western grey
      kangaroo (Macropus fuliginosus) in Western Australia (WA). The IDEXX CHEKiT Q
      Fever ELISA and CFT were used to test sera from 50 sheep and 329 head of cattle
      for anti-C. burnetii antibodies and 343 kangaroo sera were tested using an
      indirect ELISA developed specifically for this study. Faecal or urine samples
      collected from the same animals were tested with two PCR assays to identify
      active shedding of C. burnetii in excreta. Only two of the 379 ruminant sera had
      detectable levels of anti-C. burnetii antibodies according to the ELISA while the
      CFT did not detect any positive samples. In contrast 115 of the 343 western grey
      kangaroo serum samples were positive when tested with the antibody-ELISA. The
      first qPCR assay, targeting the IS1111a element, identified 41 of 379 ruminant
      and 42 of 343 kangaroo DNA samples as positive for C. burnetii DNA. The second
      qPCR, targeting the JB153-3 gene, identified nine C. burnetii DNA-positive
      ruminant samples and six positive kangaroo samples. Sequence comparisons showed
      high degrees of identity with C. burnetii. Isolation of C. burnetii from faeces
      was also attempted but was not successful. From the results presented here it
      appears that domestic ruminants may not be the most significant reservoir of C.
      burnetii in WA and that kangaroos may pose a significant threat for zoonotic
      transfer of this pathogen.

PMID- 20036084
TI  - Identification of Qnr and AAC(6')-1b-cr plasmid-mediated fluoroquinolone
      resistance determinants in multidrug-resistant Enterobacter spp. isolated from
      extraintestinal infections in companion animals.
AB  - Fluoroquinolone resistance is becoming more common in veterinary medicine.
      Resistance is due to a combination of chromosomal and plasmid-mediated
      fluoroquinolone resistance (PMQR) mechanisms. The aim of the present study was to
      screen 17 multidrug-resistant Enterobacter isolates obtained from opportunistic
      infections in companion animals for chromosomal and plasmid-mediated
      fluoroquinolone resistance determinants and to determine if they are co-located
      with other antimicrobial resistance genes including beta-lactamases. Phenotypic
      tests (biochemical identification, organic solvent tolerance testing) were
      combined with genotypic analysis (PCR, pulsed field gel electrophoresis,
      sequencing, plasmid isolation and southern blot hybridization) to characterize
      the molecular basis for fluoroquinolone resistance. Antimicrobial susceptibility
      was determined by broth microdilution for fluoroquinolone antimicrobials
      (enrofloxacin, ciprofloxacin, moxifloxacin, marbofloxacin and pradofloxacin) and
      by disk diffusion for other antimicrobials. Sixteen isolates were resistant to at
      least one of the five fluoroquinolones tested. Fourteen isolates possessed PMQR
      determinants which were identified as qnrA1 (n=3) or qnrB2 (n=11), often in
      combination with aac(6')-1b-cr (n=6). The PMQR genes were localized to large,
      transferable MDR plasmids often associated with an extended-spectrum beta
      lactamase and quinolone resistance was co-transferred with bla(SHV-12) for 10 of
      the 14 qnr-positive strains. Three isolates had wild-type topoisomerases, 11 had
      a single point mutation in gyrA (Ser83Phe or Tyr), and three had two mutations;
      one in gyrA (Ser83Ile) and one in parC (Ser80Ile). PMQR genes in clinical
      veterinary Enterobacter isolates are co-located with beta-lactamases and other
      resistance genes on large transferable plasmids. PMQR genes contribute to
      fluoroquinolone resistance when combined with topoisomerase mutations and efflux.

PMID- 20036085
TI  - Genetic diversity of Porcine reproductive and respiratory syndrome virus (PRRSV)
      in selected herds in a pig-dense region of North-Western Germany.
AB  - The Porcine reproductive and respiratory syndrome virus (PRRSV) can persist for
      several weeks in infected pigs, and readily spreads from viraemic pigs to other
      pigs as well as to other herds. In regions with dense pig populations such as the
      North-Western part of Germany the virus is endemic. The aim of this study was to
      analyse the genetic diversity of PRRSV found in 18 herds in this region, which
      had pigs with respiratory or reproductive failures, and where PRRSV had been
      demonstrated by RT-PCR. Phylogenetic trees were calculated using the complete
      nucleotide sequences of the ORF5. Of the 65 samples sequenced, five PRRSV from
      four herds were of the North American (NA; Type 2) genotype, and 60 of the
      European (EU; Type 1) genotype. To ascertain if the field PRRSV varied with time
      and to monitor the health condition of the herds they were revisited 2 years
      later. Although only two herds still reported clinical signs, PRRSV was found by
      RT-PCR in 10 of the 18 herds. Phylogenetic analysis showed that of the 23 PRRSV
      sequenced, 15 were of the European (EU) genotype. The EU genotype isolates from
      both samplings could be assigned to one of 12 clusters. There was no indication
      for the existence of herd specific clusters. ORF5 sequence identities between
      PRRSV from one herd in one cluster were either 100%, or had single base
      exchanges. These data indicate that the mutation rates for the European field
      isolates are similar to that found for the NA genotype vaccine strain used in
      Germany.

PMID- 20036086
TI  - Identification of candidate pathogens of papillomatous digital dermatitis in
      dairy cattle from quantitative 16S rRNA clonal analysis.
AB  - Although it is suspected that papillomatous digital dermatitis (PDD), an
      infectious foot disease of cattle, is caused by multiple bacteria, it remains
      unclear precisely which ones are involved in the etiology. To study the bacterial
      community, we used 16S rRNA gene sequencing of randomly selected clones based on
      PCR with minimum amplification cycles to search for organisms present in PDD
      lesions but not in healthy foot skin. The nucleotide sequences of 1525 clones
      from 5 PDD lesions (836 clones) and 4 samples of healthy foot skin (689 clones)
      were determined and grouped into 316 operational taxonomic units (OTUs) with a
      cut-off value of >99% sequence identity. Two OTUs, P-01 (143 clones; 100%
      nucleotide sequence identity with Treponema phagedenis) and P-02 (112 clones; 86%
      identity with Bacteroidetes), were detected most frequently in all PDD samples
      examined. In contrast, OTU N-01 (87 clones), showing 99% nucleotide sequence
      identity with Moraxella phenylpyruvica, was the most prevalent in the normal
      samples examined. Spirochaetes were detected in only 1 sample. Phylogenetic
      analysis showed that T. denticola-like and T. phagedenis-like spirochetes were
      the predominant groups in the PDD lesions. Detection of multiple treponemes and
      an unknown bacterium close to Bacteroides sp. at high rates by a culture
      independent approach could be evidence of the association of these organisms with
      PDD.

PMID- 20036087
TI  - Transvaginal follicular aspiration and embryo development in superstimulated
      early postpartum beef cows and subsequent fertility after artificial
      insemination.
AB  - This study was conducted to investigate in early postpartum suckled beef cows
      with and without FSH pre-stimulation: (i) the influence of the postpartum period
      on the number and quality of oocytes recovered by ovum pick-up (OPU), (ii) the
      overall efficiency of the OPU/IVP embryos from days 30 to 80 postpartum and (iii)
      if repeated OPU negatively affect fertility following a fixed-time artificial
      insemination protocol. After parturition suckled Angus cows (n = 30) were divided
      in three groups (n = 10 group(-1)). All cows were anestrous at the commencement
      of experimental treatments (30.0 +/- 3.2 days postpartum, mean +/- SD; range 25
      34 days). Group 1 treatments included: dominant follicle ablation (DFA), FSH
      treatment and OPU procedure 5 days after DFA. A total of 9 mg FSH (Ovagen) was
      administered s.c. once a day over 2 days at equal doses (4.5 + 4.5mg). For
      fertility test the cows received an intravaginal progesterone treatment from Days
      78 to 86 postpartum and were fixed-time artificially inseminated (FTAI) at 56 and
      72 h after device removal. Group 2: as cited for Group 1 with no FSH treatment.
      In both groups, OPU was repeated four times (Days 35, 49, 63 and 77 postpartum)
      and the collected oocytes classified as viable were in vitro matured, fertilized
      and presumptive embryos cultured for 8 days. Group 3 (Control FTAI): cows that
      had not previously aspirations were FTAI as Groups 1 and 2. Pregnancy was
      diagnosed by means ultrasonography 39 days after FTAI. The numbers (mean +/- SEM)
      of follicles visible and aspirated at the time of OPU in FSH-treated cows were
      greater (P < 0.05) than in non-treated cows (10.6 +/- 0.6 and 8.4 +/- 0.4 vs. 8.0
      +/- 0.5 and 4.6 +/- 0.3, respectively). Following FSH treatment, the number (mean
      +/- SEM) of recovered oocytes per cow per OPU session and percentage of viable
      oocytes were greater in the treated (P < 0.05) than in non-treated animals (3.0
      +/- 0.1 and 39.5% vs. 1.5 +/- 0.1 and 30.0%). The cleavage and embryo development
      rates were similar (P > 0.05) for both groups (14.8 and 6.4% vs. 16.6 and 5.5%).
      After FTAI the pregnancy rates were not different (P > 0.05) among groups (70, 60
      and 90% for Groups 1, 2 and 3, respectively). We can conclude that (1) FSH
      treated suckled postpartum cows can be a source of oocytes for in vitro
      fertilization and (2) repeated DFA/OPU applied during postpartum period did not
      affect the subsequent fertility following FTAI.

PMID- 20036088
TI  - Multimodality minimally invasive autopsy--a feasible and accurate approach to
      post-mortem examination.
AB  - BACKGROUND: Autopsy examination has been the bedrock of western medicine. With
      the decline in the autopsy rate secondary to the negative psychological impact to
      the deceased's relatives, the benefits of autopsy have been undermined. Minimally
      invasive autopsy has been introduced but has not been widely adopted as an
      alternative to the 'traditional' open approach. This technique not only provides
      information on the cause of death abut also minimizes the disfigurement induced
      to the deceased. Our study aims to explore the feasibility and evaluate the
      accuracy of this technique. METHODS: A series of coroner cases ordered for
      autopsy were examined by a group including an experienced forensic pathologist
      and two experienced laparoscopic surgeons using thoracoscopic, laparoscopic,
      endoluminal or endovascular approaches. The procedure was video-recorded and the
      provisional diagnoses and causes of death were made based on the findings. These
      findings were subsequently correlated with the full autopsy examination. A few
      limited clinical post-mortem examinations were also performed with consent from
      relatives. RESULTS: A total of 22 cases of minimally invasive autopsies were
      performed from November 2007 to March 2008. The median duration of the procedures
      was 78.3+/-20.7 min. Thoracoscopies and laparoscopies were performed in 18
      patients while additional arterioscopic examination with endoscope was performed
      in two patients with suspected aortic diseases. Four consented limited clinical
      autopsies were also performed: two of them involved thoracoscopic biopsies of
      lung tissues, one was a para-mortem upper endoscopy for the investigation of
      pathology of the stomach and the other one was laparoscopy for a patient, who
      died of unexplained acidosis. Comparison with full autopsies showed that the
      accuracy of the diagnosis was 94.4%, the sensitivity was 90%, the specificity was
      100%, the positive predictive value was 100% and the negative predictive value
      was 88.9%. CONCLUSION: Minimally invasive autopsy is a feasible approach,
      yielding accurate findings when compared with conventional autopsies. The former
      can be a valuable tool for obtaining more valuable information in situations when
      the next-of-kin of the deceased does not consent to a conventional autopsy.

PMID- 20036089
TI  - The impact of protein on Caco-2 permeability of low mass balance compounds for
      absorption projection and efflux substrate identification.
AB  - This study was to evaluate the mechanistic effect of protein to help better
      interpret the permeability results for compounds with low mass balance in Caco-2
      permeability assay. The absorptive or bi-directional permeability of lipophilic
      compounds with mass balance were measured across Caco-2 cell monolayers as well
      as the empty transport devices with or without protein (4% bovine serum albumin,
      BSA) added to the receiver side. The results from empty transport device study
      indicated that the filter membrane is a permeability barrier for the low mass
      balance compounds and protein increases permeability by improving the compound
      diffusivity through the filter membrane. Caco-2 permeability measured with
      protein provided better absorption projection. Assuming the amount of compound
      associated with cells as transported did not correlate with absorption. For
      efflux substrate identification using Caco-2 bi-directional permeability assay,
      protein at the receiver side had no significant effect on the conclusion
      regarding the tested compounds as efflux substrate but increased the permeability
      measurement from both transport directions. In conclusions, Caco-2 permeability
      results measured using protein-containing buffer at the receiver side for low
      mass balance compound seems to provide better correlation with in vivo
      absorption. The fact that protein at receiver side has minimal effect on efflux
      substrate identification provides scientific basis for further specific
      transporter characterization (such as P-gp or BCRP) using specific inhibitors, in
      which same concentration of inhibitor is used in both sides of the Caco-2 cell
      system and protein for optimal permeability assessment has to be avoided.

PMID- 20036090
TI  - Determination of potency of heparin active pharmaceutical ingredient by near
      infrared reflectance spectroscopy.
AB  - Potency is an important parameter for evaluation of quality of heparin active
      pharmaceutical ingredient (API). In this paper the feasibility to determine
      potency of heparin API with near infrared reflectance spectroscopy (NIRS) coupled
      with partial least squares (PLS) algorithm is attempted. PLS factors, correlation
      coefficient of calibration set (R(c)), the root mean square of cross-validation
      (RMSECV), correlation coefficient of prediction set (R(p)) and the root mean
      square of prediction (RMSEP) were used to evaluate the performance of the models.
      The optimal calibration model was obtained with R(p)=0.9721 and RMSEP=0.55 in the
      1700-1898nm spectral region when using SG-1st derivative spectral transform
      method and division of calibration/prediction samples was 1/1. Three other
      additional samples demonstrated good prediction capability of the final model and
      three validation samples gave good repeatability result. NIRS has the potential
      to be a final lot release test to be performed in a QC laboratory.

PMID- 20036091
TI  - Physico-chemical characterization of an amphiphilic cyclodextrin/genistein
      complex.
AB  - Specific recognition of cell-targeting systems as host-carriers modified with
      receptor targeting groups, is a major ambition in the application of
      supramolecular science to medicine and life science. Genistein (Gen), an
      isoflavone belonging to the class of phytoestrogens, is of great interest because
      it has been considered as potential remedy for many kinds of disease. In this
      work, genistein in aqueous medium and in the presence of an host nanocarrier as
      amphiphilic cyclodextrin (CyD) modified in the upper rim with oligoethylene
      hydroxyl groups [(2-oligo(ethyleneoxide)-6-hexylthio)-beta-CyD, SC6OH] at 1:1
      molar ratio, has been firstly investigated by UV-vis measurements coupled with
      circular dichroism data, in order to characterize the drug/macrocycle binding
      affinity through the formation of the complex. Furthermore, FTIR-ATR technique
      has been used to detect the complex formation in solid phase and to characterize
      the functional groups responsible of the solid Gen/SC6OH complex stability. The
      infrared absorbance spectra of the complex, collected in a wide range of
      wavenumber and around the physiological temperature, have been analysed and
      compared with the spectra of the pure compounds and their physical mixture. By
      monitoring the most significant changes in the shape and position of the
      absorbance bands of the Gen functional groups, we showed that the formation
      and/or modification of polar bonds play the main role in the interaction of the
      drug with the amphiphilic CyD. From the results, Gen is shown to be entangled in
      SC6OH nanoaggregates, establishing hydrogen bonding with the hydrophilic PEG
      chains.

PMID- 20036093
TI  - Fistula formation to the bladder and to a corpus alienum as a rare complication
      of diverticulitis: a case report.
AB  - BACKGROUND: Fistula formation is a known complication of diverticulitis.
      Treatment of a diverticular fistula depends on the comorbidity of the patient and
      the severity of the disease. CASE REPORT: A 59-year-old man presented to the
      Emergency Department with chronic lower back pain that was being treated with a
      neurostimulator. He presented with severe sepsis, and an abscess formation near
      the neurostimulator. An abdominal and pelvic computed tomography scan revealed
      diverticulitis complicated by fistula formation to the neurostimulator and
      bladder. He was successfully treated by a two-stage procedure: first, exploration
      and drainage of the abscess, with removal of the foreign body, followed by a
      sigmoid resection 1 week later. CONCLUSION: In rare but severe presentations of
      diverticular disease, it is very important to limit initial treatment to the most
      threatening disorder.

PMID- 20036092
TI  - Liquid chromatography-tandem mass spectrometry for the determination of
      paclitaxel in rat plasma after intravenous administration of poly(L-glutamic
      acid)-alanine-paclitaxel conjugate.
AB  - A specific and sensitive liquid chromatography-tandem mass spectrometric method
      for quantitative determination of paclitaxel in rat plasma was developed and
      validated using docetaxel as an internal standard. Liquid-liquid extraction using
      tert-butyl methyl ether was used to extract the drug and the internal standard
      from plasma. The separation of paclitaxel was performed on a C(18) column with a
      mobile phase of acetonitrile:water:formic acid (65:35:0.1, v/v/v) over 5min. The
      assay was based on the selected reaction monitoring transitions at m/z of the
      precursor-product ion transitions m/z 854.2-->286.1 for paclitaxel and 808.3-
      >527.2 for internal standard. The lower limit of quantification was 0.5ng/mL
      based on 100microL of plasma. Intra- and inter-day assay variations were less
      than 15%, and the accuracy values were between 95.4 and 105.4%. The extraction
      recoveries ranged from 96.7 to 103.7% across the calibration curve range. The
      method was successfully applied to measurement of low concentrations of
      paclitaxel or regenerated paclitaxel in plasma after intravenous administration
      of a single dose (10mg/kg) of a poly(l-glutamic acid)-alanine-paclitaxel
      conjugate to rats.

PMID- 20036094
TI  - Emergency calls for swine flu: how to deal with nuisance calls?

PMID- 20036095
TI  - Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and
      stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a
      case report.
AB  - BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke
      like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range
      of multisystemic symptoms. Epileptic seizures are common features of both MELAS
      and meningoencephalitis and are typically treated with anticonvulsants.
      OBJECTIVES: To provide the reader with a better understanding of MELAS and the
      adverse effects of valproic acid. CASE REPORT: A 47-year-old man with a history
      of diabetes, hearing loss, sinusitis, and otitis media was brought to our
      emergency department due to acute onset of fever, headache, generalized seizure,
      and agitation. Because acute meningoencephalitis was suspected, the patient was
      treated with antibiotics on an empirical basis. The seizure activity was
      aggravated by valproic acid and abated after its discontinuation. MELAS was
      suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A
      >G mutation in the mitochondrial DNA. CONCLUSION: Detailed history-taking and
      systematic review help emergency physicians differentiate MELAS from
      meningoencephalitis in patients with the common presentation of epileptic
      seizures. Use of valproic acid to treat epilepsy in patients suspected of having
      mitochondrial disease should be avoided. Underlying mitochondrial disease should
      be suspected if seizure activity worsens with valproic acid therapy.

PMID- 20036096
TI  - A nineteen-year-old girl with palpitations.

PMID- 20036097
TI  - Impact of a brief intervention on patient communication and barriers to pain
      management: results from a randomized controlled trial.
AB  - OBJECTIVE: This study examined the impact of a brief pain communication/education
      intervention on patient outcomes in breast cancer. We hypothesized that our
      intervention would improve patient communication and reduce misconceptions
      ("Barriers") concerning pain management, and that patients with lower Barriers,
      or who perceived their physician as being more facilitative and receptive, would
      report better outcomes. METHODS: Female breast cancer patients with persistent
      pain (n=89) were randomly assigned to either a 30-min in-person pain
      education/communication intervention or control condition and followed for 12
      weeks. RESULTS: Intervention group patients reported a significant decrease in
      pain Barriers but not in other outcomes. Overall, patients with lower barrier
      scores reported less distress and better emotional well-being. Patients who
      scored higher in active communication (e.g., asking questions, giving
      information) reported fewer Barriers and better pain relief. Individuals who
      perceived their physicians as being more receptive reported better pain
      management while those who perceived their physicians as being both more
      receptive and facilitative were more satisfied with their health care.
      CONCLUSION: A brief education/communication intervention reduced patients'
      Barriers to pain management but did not impact other patient outcomes. PRACTICAL
      IMPLICATIONS: Pain outcomes may be improved by addressing patients' pain
      misconceptions and emphasizing a receptive and responsive communication style.

PMID- 20036098
TI  - Do people with diabetes understand their clinical marker of long-term glycemic
      control (HbA1c levels) and does this predict diabetes self-care behaviours and
      HbA1c?
AB  - OBJECTIVE: Research demonstrates that patients have a poor understanding of
      glycosylated haemoglobin A1c (HbA1c) and that this impacts on effective diabetes
      self-management. This study attempted to replicate these findings in a UK
      outpatient sample of people with diabetes. METHOD: 83 participants were recruited
      and asked to fill in a questionnaire assessing their understanding of HbA1c,
      diabetes self-care behaviours and diabetes-specific self-efficacy in relation to
      carrying out these self-care behaviours. RESULTS: Only 26.5% of the participants
      were classified as having a good understanding of HbA1c. Correlational and
      univariate analyses indicated that this level of understanding was related to
      demographic variables, HbA1c levels and certain aspects of self-care and self
      efficacy. A series of multiple regressions found that understanding was a
      significant predictor of HbA1c levels. CONCLUSION: The majority of participants
      seemed to have a poor understanding of HbA1c and this was related to aspects of
      their diabetes management, self-efficacy and HbA1c levels. PRACTICAL
      IMPLICATIONS: These findings provide support for the application of programmes
      and initiatives aimed at improving patients understanding of clinical disease
      markers.

PMID- 20036099
TI  - Minorities in academic medicine: review of the literature.
AB  - Given the considerable demographic changes occurring in the in the United States
      coupled with the urgent need for the field of medicine to continue to adapt to
      and better align with societal needs and expectations, a growing number of
      leaders in academic medicine have called for academic health centers to redouble
      their efforts to increase the diversity of students, faculty, and staff. Although
      it is laudable to call for increased attention and efforts to diversify, it is of
      paramount importance to review and distill what we have learned from past efforts
      so that future energy can be spent intelligently to ensure greater impact going
      forward. This article reviews the literature on both the barriers and
      facilitators for racial and ethnic minorities in academic medical careers and
      offers guidance for increasing the diversity of the nation's medical school
      faculty members and leadership.

PMID- 20036100
TI  - Reactive oxygen species mediate functional differences in human radial and
      internal thoracic arteries from smokers.
AB  - OBJECTIVE: Smoking not only increases the risk that coronary heart disease will
      develop but also morbidity and mortality in patients with known coronary
      atherosclerosis and after coronary artery bypass grafting. Excessive generation
      of reactive oxygen species (ROS) has been implicated as the final common pathway
      for the development of endothelial dysfunction in various cardiovascular risk
      factors. This study assessed the influence of smoking on two different human
      arteries routinely used as coronary artery bypass graft conduits. METHODS:
      Isometric tension was recorded on discarded segments of human left internal
      thoracic artery (ITA) and the radial artery (RA) from smokers and nonsmokers.
      RESULTS: The contractile response to endothelin-1 was significantly stronger in
      arteries from smokers than in those from nonsmokers. By contrast, endothelium
      dependent relaxant responses to acetylcholine were attenuated in RA rings but
      enhanced in ITA rings from smokers. In additional experiments, 5-(&6)
      chloromethyl-2'-7'-dichlorodihydro-fluorescein diacetate (DCDHF) was used to
      photochemically detect ROS by confocal imaging of intact ITA and RA. Enhanced
      production of ROS was induced by exposure of tissues to 28 degrees C. While
      during exposure to 28 degrees C, basal fluorescence emission was unchanged in ITA
      rings, it increased significantly in RA rings, indicating enhanced formation of
      ROS in this peripheral artery. CONCLUSIONS: Data suggest that smoking induces
      endothelial dysfunction by increasing vascular ROS production. Different levels
      of endogenous antioxidant enzyme activities and the degree of atherosclerotic
      changes might modulate physiologic and pharmacologic vasoreactivity and be
      responsible for decreased graft patency of RA compared with ITA conduits,
      especially in active smokers.

PMID- 20036101
TI  - In vivo suppression of vein graft disease by nonviral, electroporation-mediated,
      gene transfer of tissue inhibitor of metalloproteinase-1 linked to the amino
      terminal fragment of urokinase (TIMP-1.ATF), a cell-surface directed matrix
      metalloproteinase inhibitor.
AB  - BACKGROUND: Smooth muscle cell (SMC) migration and proliferation are important in
      the development of intimal hyperplasia, the major cause of vein graft failure.
      Proteases of the plasminogen activator (PA) system and of the matrix
      metalloproteinase (MMP) system are pivotal in extracellular matrix degradation
      and, by that, SMC migration. Previously, we demonstrated that inhibition of both
      protease systems simultaneously with viral gene delivery of the hybrid protein
      TIMP-1.ATF, consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1)
      and the receptor-binding amino terminal fragment (ATF) of urokinase, reduces SMC
      migration and neointima formation in an in vitro restenosis model using human
      saphenous vein cultures more efficiently than both protease systems separately.
      Because use of viral gene delivery is difficult in clinical application, this
      study used nonviral delivery of TIMP-1.ATF plasmid to reduce vein graft disease
      in a murine bypass model. Nonviral gene transfer by electroporation was used to
      avert major disadvantages of viral gene delivery, such as immune responses and
      short-term expression. METHODS: Plasmids encoding ATF, TIMP-1, TIMP-1.ATF, or
      luciferase, as a control, were injected and electroporated in both calf muscles
      of hypercholesterolemic apolipoprotein E3-Leiden (APOE*3Leiden) mice (n = 8). One
      day after electroporation, a venous interposition of a donor mouse was placed
      into the carotid artery of a recipient mouse. In this model, vein graft
      thickening develops with features of accelerated atherosclerosis. Vein grafts
      were harvested 4 weeks after electroporation and surgery, and histologic analysis
      of the vessel wall was performed. RESULTS: Electroporation-mediated
      overexpression of the plasmid vectors resulted in a prolonged expression of the
      transgenes and resulted in a significant reduction of vein graft thickening (ATF:
      36% +/- 9%, TIMP-1: 49% +/- 5%, TIMP-1.ATF: 58% +/- 5%; P < .025). Although all
      constructs reduced vein graft thickening compared with the controls, the luminal
      area was best preserved in the TIMP-1.ATF-treated mice. CONCLUSION: Intramuscular
      electroporation of TIMP-1.ATF inhibits vein graft thickening in vein grafts in
      carotid arteries of hypercholesterolemic mice. Binding of TIMP-1.ATF hybrid
      protein to the u-PA receptor at the cell surface enhances the inhibitory effect
      of TIMP-1 on vein graft remodeling in vitro as well as in vivo and may be an
      effective strategy to prevent vein graft disease.

PMID- 20036102
TI  - Improving influenza vaccination rates in the workplace: a randomized trial.
AB  - BACKGROUND: To minimize absenteeism resulting from influenza, employers
      frequently offer on-site influenza vaccination to employees. Yet the level of
      uptake of vaccine is low among working adults. This study was designed to
      increase workplace influenza vaccination rates by offering both a choice of
      intranasal (LAIV) and injectable (TIV) influenza vaccines to eligible employees,
      and an incentive for being vaccinated, and by increasing awareness of the vaccine
      clinic. DESIGN: This study used a stratified randomized cluster trial.
      SETTING/PARTICIPANTS: A total of 12,222 employees in 53 U.S. companies with
      previous influenza vaccine clinics were examined. INTERVENTIONS: Control sites
      advertised and offered vaccine clinics as previously done. Choice sites offered
      LAIV or TIV and maintained their previous advertising level but promoted the
      choice of vaccines. Choice Plus sites increased advertising and promoted and
      offered a choice of vaccines and a nominal incentive. MAIN OUTCOME MEASURES:
      These included vaccination rates among eligible employees. Hierarchic linear
      modeling (HLM) was used to determine factors associated with vaccination.
      RESULTS: The overall vaccination rate increased from 39% in 2007-2008 to 46% in
      2008-2009 (p<0.001). The difference in vaccination rates for LAIV was 6.5% for
      Choice versus Control and 9.9% for Choice Plus versus Control (both p<0.001).
      Rates of TIV increased by 15.9 percentage points in the Choice Plus arm versus
      Control for workers aged > or =50 years (p=0.024). Rates of TIV did not change in
      workers aged 18-49 years in either intervention arm or in workers aged > or =50
      years in the Choice arm. In HLM analyses, factors significantly associated with
      increased vaccination were older age, female gender, previous company vaccination
      rate, and the Choice Plus intervention. CONCLUSIONS: An incentive for
      vaccination, an intensified advertising campaign, and offering a choice of
      influenza vaccines improved vaccination rates in the workplace.

PMID- 20036103
TI  - Symbol labelling improves advantageous decision-making on the Iowa Gambling Task
      in people with intellectual disabilities.
AB  - Individuals with intellectual and developmental disabilities often have
      difficulties foregoing short-term loss for long-term gain. The Iowa Gambling Task
      (IGT) has been extensively adopted as a laboratory measure of this ability. In
      the present study, we undertook the first investigation with people with
      intellectual disabilities using a two-choice child version of the IGT, with
      measures of intellectual and executive functioning. Compared to a group of
      matched controls, people with intellectual disabilities performed advantageously
      and showed high levels of subjective awareness about the relative goodness and
      badness of the decks. A symbol labelling intervention, in which participants were
      taught to label the good and bad decks at regular intervals significantly
      improved advantageous decision-making to levels approximating that of controls.
      Factor analysis of executive functioning scores identified working memory and
      mental flexibility (response initiation and set shifting), with a near
      significant inverse correlation between the extent to which the intervention was
      required and mental flexibility. These findings show, for the first time, that
      people with intellectual disabilities are capable of performing advantageously on
      the IGT and add to the growing clinical literature on decision-making.

PMID- 20036104
TI  - Staff reactions to challenging behaviour: an observation study.
AB  - Staff reactions play an important role in the development and maintaining of
      clients' challenging behaviour. Because there is a paucity of research on staff
      reactions in naturalistic settings, this study examined sequential associations
      between challenging behaviour and staff reactions by means of a descriptive
      analysis. We analysed video recordings of the reactions of 10 staff members
      towards challenging behaviour of clients with severe or profound intellectual
      disabilities who displayed self-injurious behaviour, stereotyped behaviour and/or
      aggressive/destructive behaviour. As expected, the staff members used much verbal
      behaviours after challenging behaviour and often immediately tried to stop the
      challenging behaviour. Furthermore, staff often gave attention to challenging
      behaviour whereas offering or taking away material or tasks were less frequently
      observed reactions. Reactions to aggressive/destructive behaviour and self
      injurious behaviour were quite similar. After stereotyped behaviour, not that
      many reactions occurred significantly more. Although this study has clinical
      implications and made a valuable contribution to research on staff reactions to
      challenging behaviour, more research is needed, more specifically, about the
      effectiveness of these staff reactions.

PMID- 20036105
TI  - Geoepidemiology of autoimmune liver diseases.
AB  - Autoimmune liver diseases are characterized by immune mediated injury of bile
      ducts or hepatocytes, thus including cholangiopathies such as primary biliary
      cirrhosis, primary sclerosing cholangitis, and immunoglobulin G4-associated
      cholangitis, and autoimmune hepatitis. Although the liver was one of the earliest
      recognized sites of autoimmune aggression, the aetiology of autoimmune liver
      diseases remains largely obscure and their clinical management still difficult.
      Since an ever increasing applicability of immunology to a wide variety of chronic
      diseases, basic and clinical knowledge on autoimmune liver diseases grow rapidly
      in the last few years. This review will mainly focus on the available
      geoepidemiology data of these disorders, but it will deal also on their main
      clinical characteristics, as well as mechanisms of etiopathogenesis, for each of
      the above diseases, together with their overlap forms. In particular, we will
      discuss the major underlying immunomolecular mechanisms of development, the
      genetic influences, the growing number of immuno-serological diagnostic markers,
      and the increasingly effective therapeutic possibilities.

PMID- 20036106
TI  - A T cell-binding fragment of fibrinogen can prevent autoimmunity.
AB  - The C-terminal domain of the fibrinogen gamma chain (gammaC) has been shown to
      bind to the integrins alphaIIbbeta3, alphaMbeta2 and alphaVbeta3. It has also
      been reported that a peptide derived from the alphaMbeta2-binding site of gammaC
      can suppress an animal model of multiple sclerosis, experimental autoimmune
      encephalomyelitis (EAE). Here we have truncated gammaC at position 399 to remove
      the prothrombotic alphaIIbbeta3-binding site. We show that this truncated version
      of gammaC, termed gammaC399tr, can bind to activated T cells. In addition, T
      cells incubated with gammaC399tr secreted less IFN-gamma when stimulated with
      antigen and APC; however, cytokine secretion was unaltered when T cells were
      stimulated non-specifically with a mixture of anti-CD3 and anti-CD28 antibodies.
      Thus, only antigen-dependent T cell activation is inhibited by gammaC399tr. When
      administered intraperitoneally, gammaC399tr potently inhibited actively induced
      EAE and reversed ongoing disease. We hypothesize that the ability of gammaC399tr
      to inhibit autoreactive immune responses is a result of its ability to bind
      integrins. This activity was not solely dependent on the alphaMbeta2 integrin
      binding site. When polyalanine was substituted for the alphaMbeta2-binding site,
      the resulting gammaC390polyA was still able to inhibit EAE. To our knowledge,
      this is the first demonstration that T cells can bind to fibrin (ogen), an
      important extracellular matrix protein that is deposited at sites of
      inflammation. Our results also identify gammaC399tr as a novel therapeutic
      molecule.

PMID- 20036107
TI  - Torque-fitting and resonance frequency analyses of implants in conventional
      sockets versus controlled bone defects in vitro.
AB  - The primary stability of implants should be high on insertion into fresh
      extraction sockets. Torque-fitting and resonance frequency analyses (RFA) are
      used to assess primary implant anchorage and stability. The torque-fitting and
      RFA of implants placed in conventional surgical sockets and sockets with
      controlled coronal bone defects was compared. The possible relation between
      torque-fitting and RFA was explored. O 3.3 mm x 12 mm implants were placed in 16
      sockets finalized with O 2.8mm surgical pilot drills in the right iliac crests of
      two fresh cadavers (control). In the test group, implants were placed into
      sockets prepared by O 2.8mm drill followed by O 4.2mm twist drills to a depth of
      6mm to create circumferential controlled coronal bone defects (50% bone loss).
      Primary implant stability was assessed using insertion torque values (ITV)
      followed by RFA. Mean ITV and RFA measurements for test groups (7.83+/-0.91 N cm
      and 40.88+/-3.57) were significantly lower than controls (14.80+/-1 N cm and
      66.31+/-0.9) (P<0.05). Reductions of ITV and RFA measurements in relation to bone
      defect were 47% and 38%. The existence of controlled bone defects eliminating
      contact coronally leads to decrease in torque-fitting and primary stability of
      implants. No relationship was observed between torque-fitting and RFA.

PMID- 20036108
TI  - Variable daptomycin susceptibility in patients receiving intravenous vancomycin
      for meticillin-resistant Staphylococcus aureus infections.

PMID- 20036109
TI  - Increased stability in plasma and enhanced cellular uptake of thermally denatured
      albumin-coated liposomes.
AB  - Liposomes are nano-scale vesicles that can be used as one of drug carriers. The
      liposomes are, however, plagued by rapid opsonization of them and hence making
      their circulation time in bloodstream to be shortened. In this study,
      cationically charged liposomes of which surface was modified with bovine serum
      albumin (BSA) were prepared by using electrostatic interaction between cationic
      liposomes and anionically charged BSA molecules at higher pH than isoelectric
      point (pI) of BSA. The BSA-coated liposomes (BLs) were denatured by thermal
      treatment of BL at 100 degrees C. The thermally denatured BSA-coated liposomes
      (DBLs) have mean particle diameter of 109+/-1 nm. Encapsulation of model drug,
      doxorubicin (DOX), in the liposomes was carried out by using, so called, remote
      loading method and loading efficiency of DOX in liposomes was about 90%. DBL800
      showed higher stability in plasma compared to Doxil. Results of intracellular
      uptake evaluated by flow cytometry and confocal microscopy studies showed higher
      intracellular uptake of DBL800 than that of Doxil. Consequently, the DBL, of
      which surface was complexed with denatured protein may be applicable as drug
      delivery carriers for increasing stability in plasma and enhanced cellular uptake
      efficacy of anticancer drugs.

PMID- 20036111
TI  - An aqueous extract of Ammi visnaga fruits and its constituents khellin and
      visnagin prevent cell damage caused by oxalate in renal epithelial cells.
AB  - Teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") have been
      traditionally used in Egypt as a remedy to treat kidney stones. It was the aim of
      our study to evaluate the effect of a Khella extract (KE) as well as the two
      major constituents khellin and visnagin on renal epithelial injury using LLC-PK1
      and Madin-Darby-canine kidney (MDCK) cells. Both cell lines provide suitable
      model systems to study cellular processes that are possibly involved in the
      development of a renal stone. LLC-PK1 and MDCK cell lines were exposed to 300
      microM oxalate (Ox) or 133 microg/cm(2) calcium oxalate monohydrate (COM) in
      presence or absence of 10, 50, 100 or 200 microg/mL KE. To evaluate cell damage,
      cell viability was assessed by determining the release of lactate dehydrogenase
      (LDH). KE (e.g. 100 microg/ml) significantly decreased LDH release from LLC-PK1
      (Ox: 8.46+0.76%; Ox + 100 microg/ml KE: 5.41+0.94%, p<0.001) as well as MDCK
      cells (Ox: 30.9+6.58%; Ox+100 microg/ml KE: 17.5+2.50%, p<0.001), which indicated
      a prevention of cell damage. Similar effects for KE were observed in both cell
      lines when COM crystals were added. In LLC-PK1 cells khellin and visnagin both
      decreased the % LDH release significantly in cells that were pretreated with Ox
      or COM crystals. However, khellin and visnagin exhibited different responses in
      MDCK cells. Whereas khellin slightly reduced the % LDH release after exposure of
      the cells to Ox and COM crystals, visnagin significantly decreased % LDH release
      only after COM crystal exposure. Overall both compounds were more active in LLC
      PK1 than in MDCK cells. In summary, exposure of renal epithelial cells to Ox or
      COM crystals was associated with a significant release of LDH indicating cell
      injury. Our data demonstrate that KE as well as khellin and visnagin could
      prevent renal epithelial cell damage caused by Ox and COM and could therefore
      play a potential role in the prevention of stone formation associated with
      hyperoxaluria.

PMID- 20036112
TI  - Evaluation of bone quality and quantity in osteoporotic mice--the effects of
      genistein and equol.
AB  - The technology of gene manipulation is often used in mice. A crucial point for
      osteoporosis research is the evaluation of biomechanical and morphologic
      parameters. These parameters, however, are difficult to measure in mice.
      Nevertheless, this study demonstrates the capability of using techniques for the
      evaluation of bone quality and quantity after various treatments in osteopenic
      mice. After ovariectomy, 60 C57BL/6J mice were divided into 4 groups and were fed
      a soy-free diet (C) supplemented with estradiol, genistein or equol for 3 months.
      To analyze the osteoprotective effects of the tested supplements, we evaluated
      the bone biomechanical properties, histomorphometric changes and bone mineral
      density of the proximal tibiae metaphysis. The biomechanical parameters of
      genistein (GEN) were shown to be similar to those levels observed with estradiol
      (E). The biomechanical parameters of both GEN and E were significantly superior
      to those observed with C. Supplementation with equol (EQO) demonstrated higher
      mean biomechanical values than those observed with C. The histomorphometric
      evaluation demonstrated an increased number of nodes in mice treated with GEN and
      E as compared to the mice treated with EQO and C. Treatment with E and EQO led to
      improved cortical bone, which was only partly seen with the mice treated with
      GEN. The analysis of the bone mineral density (BMD) demonstrated that treatment
      with GEN and E resulted in a significant improvement as compared to the mice
      treated with C, while the cancellous density was significantly increased in all
      of the supplementation groups. This study conclusively demonstrated that bone
      quality and quantity parameters can be measured in mice. Furthermore,
      biomechanical and morphologic evaluations were shown to be reliable for use in
      mice. Further studies may combine these techniques with gene manipulation
      technology to better understand osteoporosis. Treatment with GEN resulted in
      improved biomechanical results and enhancement of morphologic parameters.

PMID- 20036110
TI  - Lymphangiogenesis and lymphatic metastasis in breast cancer.
AB  - Lymphatic metastasis is the main prognostic factor for survival of patients with
      breast cancer and other epithelial malignancies. Mounting clinical and
      experimental data suggest that migration of tumor cells into the lymph nodes is
      greatly facilitated by lymphangiogenesis, a process that generates new lymphatic
      vessels from pre-existing lymphatics with the aid of circulating lymphatic
      endothelial progenitor cells. The key protein that induces lymphangiogenesis is
      vascular endothelial growth factor receptor-3 (VEGFR-3), which is activated by
      vascular endothelial growth factor-C and -D (VEGF-C and VEGF-D). These
      lymphangiogenic factors are commonly expressed in malignant, tumor-infiltrating
      and stromal cells, creating a favorable environment for generation of new
      lymphatic vessels. Clinical evidence demonstrates that increased lymphatic vessel
      density in and around tumors is associated with lymphatic metastasis and reduced
      patient survival. Recent evidence shows that breast cancers induce remodeling of
      the local lymphatic vessels and the regional lymphatic network in the sentinel
      and distal lymph nodes. These changes include an increase in number and diameter
      of tumor-draining lymphatic vessels. Consequently, lymph flow away from the tumor
      is increased, which significantly increases tumor cell metastasis to draining
      lymph nodes and may contribute to systemic spread. Collectively, recent advances
      in the biology of tumor-induced lymphangiogenesis suggest that chemical
      inhibitors of this process may be an attractive target for inhibiting tumor
      metastasis and cancer-related death. Nevertheless, this is a relatively new field
      of study and much remains to be established before the concept of tumor-induced
      lymphangiogenesis is accepted as a viable anti-metastatic target. This review
      summarizes the current concepts related to breast cancer lymphangiogenesis and
      lymphatic metastasis while highlighting controversies and unanswered questions.

PMID- 20036113
TI  - Gender influences Health-Related Quality of Life in IPF.
AB  - BACKGROUND: HRQL in IPF patients is impaired. Data from other respiratory
      diseases led us to hypothesize that significant gender differences in HRQL in IPF
      also exist. METHODS: Data were drawn from the NIH-sponsored Lung Tissue Research
      Consortium (LTRC). Demographic and pulmonary physiology data along with MMRC, SF
      12, and SGRQ scores from women vs. men were compared with two-sample t-tests.
      Multivariate linear regression was used to examine the association between SF-12
      component scores and gender while adjusting for other relevant variables.
      RESULTS: The study sample consisted of 147 men and 74 women. Among several
      baseline variables, only DL(CO)% predicted differed between women and men, (43.7
      vs. 38.0, p=0.03). In general, men exhibited lower (better) MMRC scores (1.7 vs.
      2.4, p=0.02), particularly those with milder disease as measured by DL(CO)%
      predicted. In an adjusted analysis, SF-12 PCS scores in men were lower (worse)
      than women (p=0.01), an effect that was more pronounced in men with greater
      dyspnea scores. In a similar analysis, SF-12 MCS scores in women were lower than
      men (worse) (48.3 vs. 54.4, p=0.0004), an effect that was more pronounced in
      women with greater dyspnea scores. CONCLUSIONS: Significant gender differences in
      HRQL exist in IPF. As compared to women, men reported less severe dyspnea, had
      worse SF-12 PCS scores, but better SF-12 MCS scores. Dyspnea appears to have a
      greater impact on the physical HRQL of men and the emotional HRQL of women. An
      improved understanding of the mechanism behind these differences is needed to
      better target interventions.

PMID- 20036114
TI  - Membrane trafficking events that partake in autophagy.
AB  - During autophagy, autophagosomes or autophagic vesicles (AVs) are formed and
      enclose portions of cytosol and/or entire organelles. Distinct from any other
      cellular vesicle, AVs have a double membrane, between which lies a very limited
      lumen. To obtain this peculiar topology, the early AV, the phagophore or
      isolation membrane (IM) must be either synthesised de novo or expanded by vesicle
      fusion. In support of the latter, recent work has implicated several different
      organelles as potential membrane sources during the initial stages of IM
      formation and expansion. Once closed, AVs use the microtubule network to meet and
      fuse with several different endocytic organelles on their way to becoming
      degradative AVs. Recent studies have shed light on the machinery required for
      both these early and late events to occur.

PMID- 20036115
TI  - Estimation of the annual production and composition of C&D Debris in Galicia
      (Spain).
AB  - One of the key aspects that must be taken into consideration within the framework
      of Sustainable Construction is the management of Construction and Demolition
      (C&D) Debris. As for other types of waste, specific handling procedures are
      required to manage C&D Debris; these include reduction, reuse, recycling, and if
      all other possibilities fail, recovery or disposal. For public planning
      strategies aimed at the management of C&D Debris to be effective, it is first
      necessary to have specific knowledge of the type of waste materials generated in
      a particular region. After verifying that the methods available to determine the
      production and composition of C&D Debris are limited, this paper presents a
      procedure to ascertain the production and composition of C&D Debris, in any
      region. The procedure utilizes data on the surface areas of newly constructed
      buildings, renovations and demolitions, which are estimated from available data
      for recent years, as well as information on the quantity of debris generated per
      surface area in any type of construction site, which is obtained from recently
      executed constructions or from the ground plans of older buildings. The method
      proposed here has been applied to Galicia, one of Spain's autonomous communities,
      for which the quantity and composition of C&D Debris have been estimated for the
      horizon year 2011.

PMID- 20036116
TI  - (89)Zr-trastuzumab PET visualises HER2 downregulation by the HSP90 inhibitor NVP
      AUY922 in a human tumour xenograft.
AB  - NVP-AUY922, a potent heat shock protein (HSP) 90 inhibitor, downregulates the
      expression of many oncogenic proteins, including the human epidermal growth
      factor receptor-2 (HER2). Because HER2 downregulation is a potential biomarker
      for early response to HSP90-targeted therapies, we used the (89)Zr-labelled HER2
      antibody trastuzumab to quantify the alterations in HER2 expression after NVP
      AUY922 treatment with HER2 positron emission tomography (PET) imaging. The HER2
      overexpressing human SKOV-3 ovarian tumour cell line was used for in vitro
      experiments and as xenograft model in nude athymic mice. In vitro HER2 membrane
      expression was assessed by flow cytometry and a radio-immuno assay with (89)Zr
      trastuzumab. For in vivo evaluation, mice received 50mg/kg NVP-AUY922
      intraperitoneally every other day. (89)Zr-trastuzumab was injected intravenously
      6d before NVP-AUY922 treatment and after 3 NVP-AUY922 doses. MicroPET imaging was
      performed at 24, 72 and 144h post tracer injection followed by ex-vivo
      biodistribution and immunohistochemical staining. After 24h NVP-AUY922 treatment
      HER2 membrane expression showed profound reduction with flow cytometry (80%) and
      radio-immuno assay (75%). PET tumour quantification, showed a mean reduction of
      41% (p=0.0001) in (89)Zr-trastuzumab uptake at 144h post tracer injection after
      NVP-AUY922 treatment. PET results were confirmed by ex-vivo (89)Zr-trastuzumab
      biodistribution and HER2 immunohistochemical staining. NVP-AUY922 effectively
      downregulates HER2, which can be monitored and quantified in vivo non-invasively
      with (89)Zr-trastuzumab PET. This technique is currently under clinical
      evaluation and might serve as an early biomarker for HSP90 inhibition in HER2
      positive metastatic breast cancer patients.

PMID- 20036117
TI  - Historical cross-trial comparisons for competing treatments in advanced breast
      cancer--an empirical analysis of bias.
AB  - PURPOSE: Randomised controlled trials (RCTs) provide optimal evidence to assess
      the benefits of new treatments. However, clinicians routinely rely on cross-trial
      comparisons to assess competing treatments when head-to-head randomised
      comparisons are unavailable. We investigate the validity of cross-trial
      comparisons using individual patient data (IPD) where patients received the same
      treatment protocol. We also examine the extent to which statistical adjustment
      for baseline characteristics can account for inter-trial differences in outcomes.
      PATIENTS AND METHODS: We used pooled IPD of 378 women with advanced breast cancer
      assigned to oral cyclophosphamide, intravenous methotrexate and 5-fluorouracil
      (CMF) in the control arms of three first-line treatment RCTs (ANZ8101, ANZ8614
      and ANZ0001) conducted between 1982 and 2001. The Kaplan-Meier method was used to
      compare progression-free survival (PFS) and overall survival (OS) across trials.
      Proportional hazard models were constructed to estimate the hazard rates across
      trials after adjustment for baseline characteristics. RESULTS: The distribution
      of baseline characteristics varied across trials. There was a statistically
      significant difference in survival among women treated with CMF in these trials
      (logrank p=0.009). The median OS were 17.7, 10.3 and 10.1 months for 0001, 8101
      and 8614, respectively. The hazard ratios for survival, adjusted for baseline
      characteristics differences, were 1.44 (8614) and 1.45 (8101) compared to 0001
      (p=0.03). PFS did not differ across trials (logrank p=0.38). CONCLUSIONS: Caution
      should be exercised when interpreting results from historical cross-trial
      comparisons even if the adjustment of baseline prognostic characteristics can be
      performed. Cross-trial comparisons have some role in hypothesis-generating,
      identifying and prioritising promising treatments for further investigation;
      however RCTs are still essential to guide sound clinical practice.

PMID- 20036118
TI  - Promoting sludge quantity and activity results in high loading rates in Anammox
      UBF.
AB  - The anaerobic ammonium oxidation (Anammox) was successfully started up in an
      upflow biofilm (UBF) reactor and operated for 435 days at 35 degrees Celsius. The
      process development could be divided into four phases, i.e. endogenous
      denitrification without Anammox reaction (P1), functional biomass enrichment
      under relatively low nitrogen loading rate (NLR) (P2), specific Anammox activity
      (SAA) enhancement with high NLR (P3) and the final stable stage (P4). The maximal
      NLR was as high as 34.5 kg N/m(3)d. Nitrogen mass balance showed that 88.84% of
      input nitrogen converted to dinitrogen gas, 1.74% was used for cellular synthesis
      and the rest was converted to nitrate. The final produced biomass was fast
      growing with SAA of 1.8 g N/gVSS d and doubling time of 4.3-7.4 d. Granulation
      and biofilm formation contributed to the biomass enrichment, while appropriate
      recirculation as well as relatively high temperature (35 degrees Celsius) helped
      to promote SAA. Effective retention time and promoted sludge activity were
      considered as the key factors for bacterial growth and efficient Anammox process.

PMID- 20036119
TI  - Asymmetric syntheses of daedalin A and quercinol and their tyrosinase inhibitory
      activity.
AB  - Stereoselective syntheses of daedalin A and quercinol, an enantiomer of daedalin
      A, is described. The tyrosinase inhibitory activities of daedalin A and quercinol
      were examined. The activity of quercinol was weaker than that of daedalin A at
      high concentration.

PMID- 20036120
TI  - Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea
      derivatives.
AB  - Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor
      antagonists. First, the SAR of the lead compound was systematically explored.
      Subsequent optimization resulted in the identification of several biaryl-based
      hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and
      very high oral bioavailability in the rat.

PMID- 20036121
TI  - 2-Arylbenzoxazoles as CETP inhibitors: substitution and modification of the alpha
      alkoxyamide moiety.
AB  - The development of a series of 2-arylbenzoxazole alpha-alkoxyamide and beta
      alkoxyamine inhibitors of cholesteryl ester transfer protein (CETP) is described.
      Highly fluorinated alpha-alkoxyamides proved to be potent inhibitors of CETP in
      vitro, and the highly fluorinated 2-arylbenzoxazole beta-alkoxyamine 4 showed a
      desirable combination of in vitro potency (IC(50)=151 nM) and oral
      bioavailability in the mouse.

PMID- 20036122
TI  - Novel phospholipid analogues of pan-PPAR activator tetradecylthioacetic acid are
      more PPAR alpha selective.
AB  - Tetradecylthioacetic acid (TTA) is a modified fatty acid that appears to improve
      insulin sensitivity, lower blood lipid levels, enhance fatty acid oxidation and
      promote anti-inflammatory action in vivo, through mechanisms partly dependent
      upon peroxisome proliferator-activated receptors (PPARs). In order to improve the
      biological efficacy of TTA as a PPAR agonist, two novel phospholipid analogue
      lyso tetradecylthioacetyl-L-alpha-phosphatidylcholine and di-tetradecylthioacetyl
      L-alpha-phosphatidylglycerol have been developed. Here we report on the syntheses
      of these novel phospholipids and their relative potential to act as PPAR agonists
      in vitro, in comparison to TTA and other positive controls.

PMID- 20036123
TI  - Solubilization and deaggregation of cobalt bis(dicarbollide) derivatives in water
      by biocompatible excipients.
AB  - In the field of medicinal chemistry, cobalt bis(dicarbollide) derivatives are
      promising therapeutic agents. The potential pharmaceutical utilization of
      metallacarboranes is complicated due to spontaneous self-assembling in water.
      This problem can be solved by using suitable deaggregating agent. We present here
      the comprehensive screen of substituted cobalt bis(dicarbollide) derivatives with
      cyclodextrin derivatives, classical surfactants and amphiphilic copolymers to
      find general biocompatible excipients. Preliminary results are obtained by using
      UV/Vis spectroscopy as the technique with the best ratio of applicable
      information to time and source dependence.

PMID- 20036124
TI  - Do risk assessment scales for pressure ulcers work?
AB  - Risk assessment scales are widely used to measure the risk of pressure ulcers in
      the clinical area. They have been subject to many validation studies; however
      these have focused on the predictive ability of the scales. We have conducted
      several studies that consider the validity of pressure ulcer risk assessment
      scales. We have reviewed these and revisited the data in some cases to conduct
      additional tests of validity presented for the first time in this paper. Based on
      these results, and a review of the literature, we have come to the conclusion
      that while the scales are probably reliable, and do assess risk: 1. Many of the
      components of risk assessment scales are not predictive of pressure ulcers. 2.
      There are other variables that are routinely available to clinicians that give
      additional predictive power. 3. The importance of components is not accurately
      reflected by their range of values. 4. Components are correlated and some
      components may be removed with no loss of predictive power. 5. There is no
      evidence the use of risk assessment scales reduces pressure ulcer incidence. The
      complexity of risk assessment scales does not appear to be warranted. There is
      evidence that clinical judgment is as effective in assessing risk as risk
      assessment scales. Reduction in pressure ulcer incidence after implementation of
      risk assessment tools is likely to be an example of the Hawthorn effect. We
      believe risk assessment scales are useful research tools, but may not be useful
      in clinical practice.

PMID- 20036125
TI  - A genomic window into the virulence of Histophilus somni.
AB  - Histophilus somni is an obligate inhabitant of the respiratory and genital
      mucosal surfaces of bovines and ovines. An individual strain can be a primary
      pathogen, an opportunistic pathogen, or a commensal, but can also move between
      these classifications if introduced into an appropriate site (e.g. the lungs)
      under conditions that favor bacterial persistence. H. somni is one of the
      bacterial agents responsible for bovine respiratory disease complex and can also
      cause a variety of systemic diseases in cattle and sheep. Isolates from disease
      sites, such as the lungs, heart, and brain, express a wide array of virulence
      factors (including biofilm formation) designed to evade host defense mechanisms.
      By contrast, some isolates from the healthy genital tract often lack many of
      these virulence factors. The genomic sequences of two bovine isolates, one from
      pneumonic lung and the other from healthy prepuce, have aided in deciphering the
      differences in phenotype and virulence between the two strains, and reveal their
      striking genetic similarity to Haemophilus influenzae and other members of the
      Pasteurellaceae.

PMID- 20036126
TI  - Evaluation of patients with multiple sclerosis using a combination of
      morphometrical features and clinical scores.
AB  - Our aim was to measure cerebellum volume (CV), sclerotic plaque numbers (PN), and
      plaque surface area (SA) in the parietal lobe, and to investigate the
      relationship between CV and PN or SA in the parietal lobe, and the clinical
      status of patients with multiple sclerosis (MS). MRIs were performed in 14
      patients with relapsing-remitting MS (RRMS), 13 patients with secondary
      progressive MS (SPMS), and 26 healthy control participants. The Cavalieri method
      was used to measure CV and SA. The cerebellum volume was significantly reduced in
      MS patients compared to controls (p < 0.01). In all patients, CV was negatively
      correlated with the duration of the disease, relapse number, and Expanded
      Disability Status Scale (EDSS) scores (p < 0.01). CV was related to mean PN in
      both the right and left parietal lobes (p < 0.01) and mean SA (p < 0.05) in RRMS
      patients; CV was also correlated with mean PN (p < 0.01) and mean SA (p < 0.05)
      in SPMS patients. The progression index (Pi) values were 2.03 +/- 0.4 in RRMS
      patients and 0.83 +/- 0.2 in SPMS patients (p = 0.023, t = 2.612) (where Pi =
      EDSS/time from onset in years). We propose that atrophy begins both in the
      supratentorial and infratentorial areas simultaneously in the RR stage, and that
      the Cavalieri method can be used to predict SPMS among patients with RRMS.

PMID- 20036127
TI  - Upper lip bite test in a patient with McCune Albright syndrome with acromegaly.
AB  - We report a patient with McCune Albright syndrome with acromegaly and features
      predictive of difficult airway except a class I upper lip bite (ULB) test. Our
      patient, a 33-year-old woman, had a history of polyostotic fibrous dysplasia.
      Tracheal intubation was performed under general anaesthesia. Although we did not
      find any difficulty in visualizing the glottis by direct laryngoscopy; our
      patient had multiple poor predictive signs of airway assessment including a
      Mallampati grade III, restricted neck movement and macroglossia. Our report
      suggests that the ULB test in people with acromegaly may act as an indicator of
      easy intubation in spite of other poor predictive signs. However, this finding
      needs further corroboration by a large study to evaluate the role of the ULB test
      in people with acromegaly.

PMID- 20036128
TI  - Effects of citicoline used alone and in combination with mild hypothermia on
      apoptosis induced by focal cerebral ischemia in rats.
AB  - The effects of citicoline used either alone or in combination with hypothermia on
      the suppression of apoptotic processes after transient focal cerebral ischemia
      were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2
      hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The
      treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group
      3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees
      C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and
      after sacrifice and transcardiac perfusion, immunohistochemical studies were
      performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score
      (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5
      (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; p<0.05). There was higher expression of
      caspase-3 proteins in Group 2 (2.28+/-0.95) compared to Group 5 (1.50+/-0.83;
      p<0.05). Bax proteins were also increased in Group 2 (1.85+/-1.06) compared to
      Group 5 (0.40+/-0.54) and in Group 4 (2.00+/-0.00) compared to Group 5 (0.40+/
      0.54; p<0.05). Significant differences in caspase-9 immunostaining scores were
      found in Group 2 (2.29+/-0.96) compared to Group 5 (0.20+/-0.44) (p<0.05); Group
      3 (1.00+/-0.70) compared to Group 5 (0.20+/-0.44; p<0.05); and Group 4 (3.00+/
      0.00; p<0.05) compared to Group 5 (0.40+/-0.54; p<0.05). Thus by suppressing
      apoptotic processes citicoline with hypothermia is more effective than either
      used alone in ameliorating cerebral damage after transient focal ischemia.

PMID- 20036129
TI  - Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of
      soluble guanylyl cyclase.
AB  - Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates
      the second messenger cGMP and hence, leads to a number of physiological responses
      including vasodilation, inhibition of platelet aggregation and neurotransmission.
      Whilst many activating and stimulating modulators of sGC were identified and
      studied in recent years, only two selective inhibitors are known: ODQ and NS
      2028. Furthermore, a synthetic approach to these inhibitors has not been reported
      yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as
      well as the preparation of three different classes of NS 2028 analogues.
      Biological evaluation of this library using rat aortic smooth muscle cells
      revealed four new compounds with good to moderate sGC inhibitory activity. Our
      experiments underline the major importance of the oxadiazole ring in ODQ and NS
      2028 for the efficiency of this class of inhibitors.

PMID- 20036130
TI  - Synthesis of 6-N-(benzothiazol-2-yl)deoxyadenosine and its exciton-coupled
      circular dichroism.
AB  - 6-N-(Benzothiazol-2-yl)deoxyadenosine (A(BT)) was synthesized and incorporated
      into DNAs. Although, the multipoint benzothiazole (BT) modification of
      oligodeoxynucleotides reduced the stability of duplexes with their complementary
      strands, it induced the strong exciton coupling between BT moieties. The circular
      dichroism (CD) spectra of this exciton coupling interaction were observed at
      wavelengths above 300nm and overlapping with the UV absorption bands of
      nucleotides could be avoided. The shapes of the CD spectra due to this
      interaction were strongly influenced by the helicity of two BT groups.

PMID- 20036132
TI  - Biosynthesis, regulation and functions of tocochromanols in plants.
AB  - Tocopherols and tocotrienols have been originally identified as essential
      nutrients in mammals based on their vitamin E activity. These lipid-soluble
      compounds are potent antioxidants that protect polyunsaturated fatty acids from
      lipid peroxidation. The biosynthesis of tocopherols and tocotrienols occurs
      exclusively in photosynthetic organisms. The biosynthetic precursors and the
      different pathway intermediates have been identified by biochemical studies and
      the different vitamin E biosynthetic genes (VTE genes) have been isolated in
      several plants and cyanobacteria. The characterization of transgenic plants
      overexpressing one or multiple VTE genes combined with the study of vitamin E
      deficient mutants allows from now on understanding the regulation and the
      function of tocopherols and tocotrienols in plants.

PMID- 20036131
TI  - Lobeline esters as novel ligands for neuronal nicotinic acetylcholine receptors
      and neurotransmitter transporters.
AB  - Vesicular monoamine transporter-2 (VMAT2) is a viable target for development of
      pharmacotherapies for psychostimulant abuse. Lobeline (1) is a potent antagonist
      at alpha4beta2 * nicotinic acetylcholine receptors, has moderate affinity
      (K(i)=5.46microM) for VMAT2, and is being investigated currently as a clinical
      candidate for treatment of psychostimulant abuse. A series of carboxylic acid and
      sulfonic acid ester analogs 2-20 of lobeline were synthesized and evaluated for
      interaction with alpha4beta2 * and alpha7 * neuronal nicotinic acetylcholine
      receptors (nAChRs), the dopamine transporter (DAT), serotonin transporter (SERT)
      and VMAT2. Both carboxylic acid and sulfonic acid esters had low affinity at
      alpha7 * nAChRs. Similar to lobeline (K(i)=4nM), sulfonic acid esters had high
      affinity at alpha4beta2 * (K(i)=5-17nM). Aromatic carboxylic acid ester analogs
      of lobeline (2-4) were 100-1000-fold less potent than lobeline at alpha4beta2 *
      nAChRs, whereas aliphatic carboxylic acid ester analogs were 10-100-fold less
      potent than lobeline at alpha4beta2 *. Two representative lobeline esters, the 10
      O-benzoate (2) and the 10-O-benzenesulfonate (10) were evaluated in the (36)Rb(+)
      efflux assay using rat thalamic synaptosomes, and were shown to be antagonists
      with IC(50) values of 0.85microM and 1.60microM, respectively. Both carboxylic
      and sulfonic acid esters exhibited a range of potencies (equipotent to 13-45-fold
      greater potency compared to lobeline) for inhibiting DAT and SERT, respectively,
      and like lobeline, had moderate affinity (K(i)=1.98-10.8microM) for VMAT2. One of
      the more interesting analogs, p-methoxybenzoic acid ester 4, had low affinity at
      alpha4beta2 * nAChRs (K(i)=19.3microM) and was equipotent with lobeline, at VMAT2
      (K(i)=2.98microM), exhibiting a 6.5-fold selectivity for VMAT2 over alpha4beta2
      nAChRs. Thus, esterification of the lobeline molecule may be a useful structural
      modification for the development of lobeline analogs with improved selectivity at
      VMAT2.

PMID- 20036133
TI  - Three-dimensional demonstration of the collateral circulation to the artery of
      Adamkiewicz via the thoracodorsal artery with multi-slice computed tomography
      angiography.

PMID- 20036134
TI  - Long-term outcomes after surgery for rheumatic mitral valve disease: valve repair
      versus mechanical valve replacement.
AB  - OBJECTIVES: Although mitral valve (MV) repair is known to be superior to
      replacement in overall clinical outcomes, the appropriateness of valve repair for
      rheumatic MV disease remains controversial because of the risks of recurrent
      mitral dysfunction and the need for re-operation. METHODS: From 1997 to 2007, 540
      patients underwent either isolated MV repair (n=122) or replacement with a
      mechanical prosthesis (n=418) in treatment of rheumatic MV disease. Survival and
      morbidity were evaluated using Kaplan-Meier analysis and Cox regression,
      including propensity score analysis. RESULTS: Follow-up was complete in 96.1% of
      patients (mean, 71.8+/-39.1 months). Patients undergoing repair were younger;
      more likely to have predominant mitral regurgitation; and less likely to show
      atrial fibrillation (AF), significant tricuspid regurgitation or pulmonary
      hypertension, than those undergoing replacement. The 10-year freedom from cardiac
      death rate was 92.0+/-4.2% following repair and 86.8+/-2.3% following replacement
      (P=0.042). After adjustment for baseline differences, repair and replacement were
      found to be similar in terms of cardiac survival (P=0.25), re-operation (P=0.68)
      and thrombo-embolic complication (P=0.20) rates. Replacement patients had more
      anticoagulation therapy-related complications (P=0.030). Independent factors
      positively associated with combined cardiac death and major morbidities included
      older patient age (P=0.010), uncorrected AF (P=0.015) and the presence of
      significant tricuspid regurgitation (P=0.012) or coronary disease (P=0.043). The
      influence of the type of MV surgery was statistically marginal (P=0.093).
      CONCLUSIONS: When performed for selected patients, MV repair had excellent
      durability comparable to mechanical valve replacement in rheumatic disease. Both
      MV repair and replacement had comparable long-term clinical results; therefore,
      repair surgery seems to be more beneficial by avoiding troublesome life-long
      anticoagulation and risks of bleeding.

PMID- 20036135
TI  - Surgical approach to the management of Brucella endocarditis.
AB  - OBJECTIVE: Brucella endocarditis is a rare complication of Brucella infection;
      however, it is the major cause of deaths in those infected with this disease. In
      this study, we aim to discuss the results of seven cases who underwent surgery
      for Brucella endocarditis in our clinic using the knowledge gathered through the
      literature. METHODS: We reviewed seven patients with Brucella endocarditis, who
      underwent surgery in our department between October 1990 and April 2007. Brucella
      endocarditis was diagnosed by physical examination, laboratory findings,
      serological tests, blood culture, transthoracic and trans-oesophageal
      echocardiography. All cases underwent surgery after 4-6 weeks of medical therapy.
      Antimicrobial treatment was maintained for an average of 6 months after surgery.
      The mean follow-up was 27.4 months. RESULTS: The mean age was 30 years (range, 5
      47 years). Four of the patients were male. Of the cases, aortic valve replacement
      (AVR) was performed in three, mitral valve replacement (MVR) was performed in
      three and combined aortic and mitral valve replacement (AVR+MVR) was performed in
      one patient. Pericardial tube drainage was done in one patient because of
      pericardial effusion and cardiac tamponade that developed 13 days after surgery.
      One (14.3%) of our patients died 15 days after surgery. The others were
      discharged. CONCLUSIONS: We concluded that medical and surgical treatment had to
      be performed simultaneously for the successful management of Brucella
      endocarditis, a fatal complication of Brucella infection.

PMID- 20036136
TI  - Diabetes and survival after coronary artery bypass grafting: comparison with an
      age- and sex-matched population.
AB  - OBJECTIVE: Long-term outcome after coronary artery bypass grafting is worse in
      diabetic than in non-diabetic patients. No data are currently available regarding
      survival rates of diabetic and non-diabetic patients after coronary
      revascularisation compared with cohorts from the general population in the
      Netherlands, which were matched for age and sex (normal Dutch survival). METHODS:
      We retrospectively analysed the data from 10626 patients who underwent coronary
      artery bypass grafting between January 1998 and December 2007. Of these, 8287
      patients were non-diabetic, 1587 were non-insulin-dependent and 630 were insulin
      dependent diabetic patients (122 patients were lost to follow-up). Survival of
      these patient groups was compared with the normal Dutch survival. RESULTS:
      Multivariate analyses revealed non-insulin-dependent diabetes to be a risk factor
      for early mortality and both insulin-dependent and non-insulin-dependent diabetes
      as risk factors for late mortality. The 1-, 5- and 10-year survival rates for non
      diabetic patients were 94.1%+/-0.3%, 86.8%+/-0.4% and 75.1%+/-1.7%, respectively,
      which was better than the normal Dutch survival. For insulin-dependent diabetic
      patients, 1-, 5- and 10-year survival rates were 90.3%+/-1.2%, 78.0%+/-2.0% and
      60.5%+/-4.6%, respectively, and for non-insulin-dependent diabetic patients
      91.4%+/-0.7%, 79.0%+/-1.3% and 58.9%+/-3.4%, respectively, which was worse than
      the normal Dutch survival. CONCLUSIONS: Non-insulin-dependent diabetes was a risk
      factor for early mortality and both types of diabetes were risk factors for late
      mortality after revascularisation. Compared with age- and sex-matched cohorts
      from the general Dutch population, the 10-year survival of non-diabetic patients
      was better; whereas the survival of both types of diabetic patients was worse.

PMID- 20036137
TI  - Editorial comment: mediastinal restaging: has the Holy Grail been found?

PMID- 20036139
TI  - Fullerene-C60/liposome complex: Defensive effects against UVA-induced damages in
      skin structure, nucleus and collagen type I/IV fibrils, and the permeability into
      human skin tissue.
AB  - We previously reported biological safety of fullerene-C60 (C60) incorporated in
      liposome consisting of hydrogenated lecithin and glycine soja sterol, as Liposome
      Fullerene (0.5% aqueous phase; a particle size, 76nm; Lpsm-Flln), and its
      cytoprotective activity against UVA. In the present study, Lpsm-Flln was
      administered on the surface of three-dimensional human skin tissue model, rinsed
      out before each UVA-irradiation at 4 J/cm(2), and thereafter added again,
      followed by 19-cycle-repetition for 4 days (sum: 76 J/cm(2)). UVA-caused corneum
      scaling and disruption of epidermis layer were detected by scanning electron
      microscopy. Breakdown of collagen type I/IV, DNA strand cleavage and
      pycnosis/karyorrhexis were observed in vertical cross-sections of UVA-irradiated
      skin models visualized with fluorescent immunostain or Hoechst 33342 stain. These
      skin damages were scarcely repressed by liposome alone, but appreciably repressed
      by Lpsm-Flln of 250 ppm, containing 0.75 ppm of C60-equivalent to a 1/3300-weight
      amount vs. the whole liposome. Upon administration with Lpsm-Flln [16.7 microM
      (12 ppm): C60-equivalent] on human abdomen skin biopsies mounted in Franz
      diffusion cells, C60 permeated after 24h into the epidermis at 1.86 nmol/g tissue
      (1.34 ppm), corresponding to 0.3% of the applied amount and a 9.0-fold dilution
      rate, but C60 was not detected in the dermis by HPLC, suggesting no necessity for
      considering a toxicity of C60 due to systemic circulation via dermal veins. Thus
      Lpsm-Flln has a potential to be safely utilized as a cosmetic anti-oxidative
      ingredient for UVA-protection.

PMID- 20036140
TI  - Controversies of prophylactic hypothermia and the emerging use of brain tissue
      oxygen tension monitoring and decompressive craniectomy in traumatic brain
      injured children.
AB  - BACKGROUND: Despite being the leading cause of death and disability in the
      paediatric population, traumatic brain injury (TBI) in this group is largely
      understudied. Clinical practice within the paediatric intensive care unit (PICU)
      has been based upon adult guidelines however children are significantly different
      in terms of mechanism, pathophysiology and consequence of injury. AIM: To review
      TBI management in the PICU and gain insight into potential management strategies.
      METHOD: To conduct this review, a literature search was conducted using MEDLINE,
      PUBMED and The Cochrane Library using the following key words; traumatic brain
      injury; paediatric; hypothermia. There were no date restrictions applied to
      ensure that past studies, whose principles remain current were not excluded.
      RESULTS: Three areas were identified from the literature search and will be
      discussed against current acknowledged treatment strategies: Prophylactic
      hypothermia, brain tissue oxygen tension monitoring and decompressive
      craniectomy. CONCLUSION: Previous literature has failed to fully address
      paediatric specific management protocols and we therefore have little evidence
      based guidance. This review has shown that there is an emerging and ongoing trend
      towards paediatric specific TBI research in particular the area of moderate
      prophylactic hypothermia (MPH).

PMID- 20036141
TI  - Cognitive functioning of postmenopausal breast cancer patients before adjuvant
      systemic therapy, and its association with medical and psychological factors.
AB  - PURPOSE: This study aimed to identify medical and psychological predictors for
      cognitive performance of breast cancer (BC) patients before the start of adjuvant
      systemic treatment and to compare cognitive performance between BC patients and
      healthy controls adjusting for medical and psychological variables. MATERIAL: 205
      postmenopausal BC patients underwent pre-treatment neuropsychological tests and
      provided medical and psychological data. 124 healthy controls underwent the same
      assessment. RESULTS: 'Treatment for diabetes mellitus' and/or 'hypertension',
      'less hours spent on cognitively stimulating activities', 'fewer days since
      surgery' and 'more reproductive years' were associated with worse cognitive
      performance in the BC patients, independent of age and IQ. Cognitive differences
      between BC patients and healthy controls could partly be explained by the
      evaluated variables. CONCLUSION: The results stress the need for adjustment for
      pre-treatment cognitive differences between study groups, and also indicate that
      further research into pre-treatment cognitive dysfunction is warranted.

PMID- 20036142
TI  - An extract based on the medicinal mushroom Agaricus blazei Murill stimulates
      monocyte-derived dendritic cells to cytokine and chemokine production in vitro.
AB  - The edible mushroom Agaricus blazei Murill (AbM), which has been used in
      traditional medicine against a range of diseases and possess immunomodulating
      properties, probably due to its high content of beta-glucans. Others and we have
      demonstrated stimulatory effects of extracts of this mushroom on different immune
      cells. Dendritic cells are major directors of immune function. We wanted to
      examine the effect of AbM stimulation on signal substance release from monocyte
      derived dendritic cells (MDDC). After 6d incubation with IL-4 and GM-CSF, the
      cells were true MDDC. Then the cells were further incubated with up to 10% of the
      AbM-based extract, AndoSan, LPS (0.5 microg/ml) or PBS control. We found that the
      AbM extract promoted dose-dependent increased levels of IL-8, G-CSF, TNFalpha, IL
      1beta, IL-6 and MIP-1beta, in that order. The synthesis of IL-2, IL-8 and
      IFNgamma were similar for the AbM extract and LPS. However, AndoSan induced a 10-
      to 2-fold higher production than did LPS of G-CSF, TNFalpha and IL-1beta,
      respectively. AbM did not induce increased synthesis of Th2 or anti-inflammatory
      cytokines or the Th1 cytokine IL-12. We conclude that stimulation of MDDC with an
      AbM-based extract resulted in increased production of proinflammatory,
      chemotactic and some Th1-type cytokines in vitro.

PMID- 20036143
TI  - Signaling pathway underlying the up-regulatory effect of TNF-alpha on the
      Na(+)/K(+) ATPase in HepG2 cells.
AB  - The activity of the Na(+)/K(+) ATPase was shown to be reduced during apoptosis
      and enhanced during cell proliferation. This work investigated whether TNF-alpha
      exerts also opposite effects on the Na(+)/K(+) ATPase in HepG2 cells and whether
      these effects are time-dependent. A time response study demonstrated that the
      activity and protein expression of the ATPase are decreased at 1h and increased
      at 4, 6 and 8h. This work focused on the up-regulatory 4h-response. TNF-alpha was
      shown to exert a stimulatory effect on cJNK and NF-kappaB and an inhibitory
      effect on caspases which, in the basal state, down-regulate the ATPase. The
      cytokine was found to target the caspases by activating JNK which in turn
      activates NF-kappaB. The activated transcription factor inhibits the caspases and
      frees the ATPase from their inhibitory action leading thus to its up-regulation.

PMID- 20036144
TI  - The role of the immune system in the initiation and persistence of the Euprymna
      scolopes--Vibrio fischeri symbiosis.
AB  - The squid-vibrio symbiosis is an experimental system being studied as a model of
      the chronic colonization of animal epithelia by bacterial partners. One principal
      question being asked with this model is: what is the role of the immune system in
      the dynamics of the onset and maintenance of the symbiotic state? This review
      focuses upon results of research to date, which have demonstrated that both cell
      mediated and cell-free components of the innate immune system are involved in
      these processes.

PMID- 20036145
TI  - Is an intrauterine device a contraindication for uterine artery embolization? A
      study of 20 patients.
AB  - The presence of an intrauterine device (IUD) has been traditionally considered a
      risk factor for postprocedural infection in patients undergoing uterine artery
      embolization (UAE). The authors retrospectively evaluated the occurrence of
      infectious complications following embolization in 20 women with IUDs. After a
      mean follow-up of 20.5 months, none of the patients developed an infectious
      complication. One patient required hysterectomy following embolization for
      persistent pain. Pathologic evaluation of the hysterectomy specimen demonstrated
      ischemia without evidence of inflammation. This experience suggests that the
      presence of an IUD might not be considered a contraindication for UAE.

PMID- 20036146
TI  - Endovascular revascularization of diseased native arteries following failed
      aortoiliac and femoropoliteal grafts: report of two cases.
AB  - Arterial reconstructions for lower-extremity ischemia, comprising aortoiliac,
      aortofemoral, and femoropopoliteal bypasses, and other procedures, have an
      intrinsic tendency to fail as time elapses. Surgical approaches to arteries in
      patients who have failed bypass grafts are often rendered more difficult, or even
      impossible to use, by surgical scarring or infection. The authors report two
      cases in which the diseased native arteries treated with failed aortoiliac and
      femoropopliteal bypass grafts were successfully recanalized with primary stent
      placement. Our cases show that stent placement of the diseased native arteries
      can represent a possible option for the treatment of failed bypass grafts.

PMID- 20036147
TI  - Short-term infection in cuffed versus noncuffed small bore central catheters: a
      randomized trial.
AB  - PURPOSE: To determine if a polyester cuff offered benefit in jugular small-bore
      central catheters (SBCCs). MATERIALS AND METHODS: Eighty-four patients were
      randomly assigned to receive a 5-F single- or 6-F dual-lumen SBCC with (n = 42)
      or without (n = 42) a polyester cuff. Follow-up was performed at 2 weeks, 1
      month, and 3 months or at catheter removal, whichever came first. At scheduled
      follow-up, catheter function, patient satisfaction, and infection were
      determined. At catheter removal, tip culture was performed to determine
      colonization and jugular vein patency was determined with ultrasonography (US).
      RESULTS: The overall infection rate was 0.4 per 1,000 catheter days. There was
      one clinical infection (noncuffed catheter). Colonization occurred in two
      noncuffed catheters and one cuffed catheter. There was one catheter dislodgment
      in the noncuffed group and none in the cuffed group. Cuffed catheters were no
      more difficult to insert but took slightly longer to remove (6 minutes +/- 4.7 vs
      5 minutes +/- 3, P = .39) and often required local anesthesia for removal,
      whereas noncuffed catheters did not (41% vs 0%, P = .001). Partial (two cuffed, 0
      noncuffed) or complete (two cuffed, one noncuffed) jugular thrombosis was seen on
      five of 58 completion US studies (8.6%). CONCLUSIONS: A polyester cuff on a SBCC
      confers no significant benefit in short-term colonization rates. Infection in
      SBCCs is uncommon. Despite their small diameters, SBCCs can result in jugular
      thrombosis, an important consideration in any patient requiring long-term venous
      access.

PMID- 20036148
TI  - Re: Penetration of Gunther tulip filter struts through an introducer sheath-case
      report and safety concerns.

PMID- 20036149
TI  - Tissue plasminogen activator in the percutaneous drainage of splenic abscess.

PMID- 20036150
TI  - Hepatic vein pseudoaneurysm after radiofrequency ablation of recurrent
      intrahepatic cholangiocarcinoma managed with stent-graft placement.

PMID- 20036151
TI  - Transient CT hyperattenuation after Merci clot retrieval and intraarterial
      thrombolysis in acute stroke mimicking subarachnoid hemorrhage.
AB  - Unenhanced computed tomography (CT) revealed hyperattenuating lesions in two
      patients with acute stroke immediately after clot retrieval with the Merci device
      in one patient and after intraarterial thrombolysis in the other. These areas of
      hyperattenuation were noted in the middle cerebral artery territory in the first
      patient and involving the brainstem, cerebellum, and tentorium in the second.
      Both were falsely interpreted as subarachnoid hemorrhage. The area of
      hyperattenuation resolved within a few hours in both patients, reflecting
      contrast medium extravasation/leakage. This report highlights the need to improve
      physician skill in recognizing contrast medium extravasation that is common
      following neuroendovascular procedures, which are becoming commonplace in modern
      day medicine.

PMID- 20036152
TI  - Epidural anesthesia for cesarean section in a patient with severe mitral stenosis
      and pulmonary hypertension.

PMID- 20036153
TI  - Failure of double-lumen tube cuff deflation on the cuff leak test.

PMID- 20036154
TI  - Iatrogenic oropharyngeal injury and hemorrhage requiring blood transfusions
      during insertion of transesophageal echocardiographic probes in patients
      undergoing cardiac surgery.

PMID- 20036155
TI  - Guidewire entrapment in a tricuspid valve apparatus.

PMID- 20036156
TI  - Anesthesia for combined cardiac surgery and liver transplant.
AB  - OBJECTIVE: To describe aspects of anesthesia for combined cardiac surgery and
      orthotopic liver transplant (OLT). DESIGN: Retrospective case series. SETTING:
      Hospital with cardiac surgery and liver transplant programs. PARTICIPANTS: Nine
      patients between September 1998 and July 2006. INTERVENTION: Combined cardiac
      surgery and OLT. MEASUREMENT AND MAIN RESULTS: Demographic and outcome data were
      recorded for each patient. Multiple intraoperative parameters were collected at
      baseline, after induction of anesthesia, after cardiac surgery, and after OLT.
      Five patients underwent combined OLT and coronary artery bypass graft (CABG)
      surgery. Four patients underwent combined OLT and aortic valve replacement (AVR)
      to relieve aortic stenosis. One of these 4 patients also had a saphenous vein
      graft to the left anterior descending artery. The CABG/OLT patients had
      hypertension, diabetes, or both, and multiple coronary arteries were affected
      although ejection fraction was preserved. The 1 death in this group was unrelated
      to a coronary event. The AVR/OLT patients had aortic stenosis that met American
      Heart Association guidelines for AVR. One death, within 24 hours of surgery, was
      associated with severe pulmonary artery hypertension. The median transfusion
      volumes were 12 units of packed red blood cells, 22 units of fresh frozen plasma,
      and 30 units of platelets. Three of the 9 patients required renal replacement
      therapy postoperatively. The median duration of intubation was 2 days, and length
      of stay in the intensive care unit was 5.5 days. CONCLUSION: Combined cardiac and
      OLT surgery is complex and serious morbidity occurs, but successful outcomes are
      attainable.

PMID- 20036157
TI  - Cytomegalovirus beta2.7 RNA transcript protects endothelial cells against
      apoptosis during ischemia/reperfusion injury.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury causes endothelial cell (EC)
      dysfunction and can precipitate apoptosis. Complex I of the mitochondrial
      respiratory chain is a target for I/R injury. The beta2.7 RNA transcript encoded
      by human cytomegalovirus (CMV) has been shown to stabilize Complex I by direct
      physical interaction. In this study, we investigated whether stabilizing Complex
      I in EC in an in vitro model of ischemia could prevent apoptosis. METHODS:
      Lentiviral vectors expressing a full-length beta2.7 RNA were generated from a
      human immunodeficiency virus-1 (HIV-1) construct, in which the viral promoter had
      been inactivated and virtually all the viral accessory proteins deleted in order
      to maximize safety. beta2.7 gene expression in transduced endothelial cells was
      examined by reverse transcript-polymerase chain reaction (RT-PCR). EC were
      prepared from rat aorta. An in vitro hypoxia/reperfusion (H/R) and I/R injury
      models were set up and apoptosis was assessed using caspase-3 activity. Reactive
      oxygen species (ROS) production in the endothelial cells was assessed by the
      capacity to oxidize non-fluorescent dihydrorhodamine-123 (DHR-123) to fluorescent
      rhodamine-123 and measured by flow cytometry. RESULTS: H/R and I/R injury induced
      formation of ROS and EC apoptosis. Overexpression of the viral beta2.7 RNA, which
      stabilizes Complex I, reduced ROS production and inhibited EC apoptosis.
      CONCLUSIONS: beta2.7 RNA is a novel effector molecule that can protect rat aortic
      endothelial cells from I/R injury causing apoptosis. As a non-coding RNA, beta2.7
      RNA will not induce an immune response in the recipient. We have shown that
      overexpression of beta2.7 RNA can protect RAEC from H/R- or I/R-mediated
      apoptosis by reduction of ROS formation.

PMID- 20036158
TI  - Severe aortic regurgitation and reduced left ventricular ejection fraction:
      outcomes after isolated aortic valve replacement and combined surgery.
AB  - BACKGROUND: In patients with severe aortic regurgitation and reduced left
      ventricular ejection fraction (LVEF), uncertainty remains whether to recommend
      aortic valve replacement (AVR) over heart transplantation, especially when mitral
      regurgitation and/or coronary heart disease coexist. METHODS: We assessed
      outcomes in 26 consecutive AVR patients aged </=70 years with severe aortic
      regurgitation and reduced LVEF, comparing the group undergoing isolated AVR with
      the group requiring combined surgery. RESULTS: The difference in mortality and
      morbidity between the groups was 10% vs 6%, which was not significant (p = 0.6 in
      both cases). Also observed was a significant improvement in functional class and
      a reduction in LV end-diastolic diameter from a median value of 69 to 64 mm in
      the isolated AVR group and to 66 mm in the combined group (p < 0.05).
      CONCLUSIONS: AVR in patients with symptomatic severe aortic regurgitation and
      reduced LVEF is feasible, even in the presence of concomitant mitral
      regurgitation and/or coronary heart disease requiring a combined surgical
      procedure.

PMID- 20036159
TI  - Relaxin is a candidate drug for lung preservation: relaxin-induced protection of
      rat lungs from ischemia-reperfusion injury.
AB  - BACKGROUND: Pulmonary injury leading to early allograft dysfunction is caused by
      ischemia-reperfusion injury (IR) and originates from multiple pathogenic events,
      including endothelial damage, neutrophil extravasation into tissue, and
      peroxidation of cell membrane lipids, followed by pulmonary cell alterations and
      edema. The potent vasoconstrictor and proinflammatory mediator endothelin (ET)-1
      plays a major role in this cascade. This study was conducted to determine whether
      treatment with relaxin, an anti-inflammatory and vasoactive hormone, prevents IR.
      METHODS: Isolated male Wistar rat lungs were perfused in a recirculatory model in
      the presence of 5-nmol/liter relaxin (n = 17) or vehicle alone (n = 14). After IR
      (60 minutes each) we determined wet-to-dry weight ratio, and levels of ET-1,
      neutrophil elastase (NE), myeloperoxidase (MPO), and malondialdehyde (MDA).
      RESULTS: IR lungs displayed significantly elevated W/D ratios after IR compared
      with control lungs (p = 0.001). In the presence of relaxin, the values obtained
      under IR conditions were significantly reduced compared with those in the vehicle
      treated IR group, but not significantly different from those obtained in the
      control + relaxin group (p = 0.079). The IR-stimulated increase in ET-1, NE, MPO,
      and MDA (3.6-, 8.4-, 6.0- and 3.0-fold over baseline, p < 0.001) was
      significantly reduced by relaxin (p < 0.007). CONCLUSION: These results show that
      human relaxin exerts a protective effect in IR-induced lung injury, likely due to
      ET reduction, endothelial protection, decreased leukocyte recruitment, and
      hindrance of free radical-mediated tissue injury, which renders relaxin a
      candidate drug for lung preservation.

PMID- 20036160
TI  - Gal knockout pig pericardium: new source of material for heart valve
      bioprostheses.
AB  - BACKGROUND: Although glutaraldehyde fixation is known to reduce immunogenicity
      and degeneration of heart valve bioprostheses, some degree of immunogenicity
      persists, which may trigger calcification. The aims of this study were to: (1)
      define the role of alpha-1,3-galactosyltransferase (alpha-Gal) antigen in valve
      calcification by comparing alpha-Gal-positive and alpha-Gal-deficient (GT-KO) pig
      pericardium; and (2) elucidate the role of human anti-Gal antibodies in the
      process of calcification and to determine the potential influence of different
      tissue-fixation techniques. METHODS: Glutaraldehyde-treated pericardium from
      alpha-Gal-positive and GT-KO pigs, with or without pre-labeling with human anti
      Gal antibodies, were implanted in rats during 1 month. RESULTS: In glutaraldehyde
      fixed pericardium, calcification levels were significantly lower in GT-KO pig
      pericardium (132.8 +/- 5.8 microg/mg) as compared with alpha-Gal-positive pig
      pericardium (155.7 +/- 7.1 microg/mg) (p < 0.015). In glutaraldehyde-fixed pig
      pericardium followed by a mix of formaldehyde, ethanol and Tween 80 (FET), the
      calcification levels were lower in GT-KO pig pericardium (0.35 +/- 0.1 microg/mg)
      as compared with alpha-Gal-positive pig pericardium (4.6 +/- 4.2 microg/mg). In
      glutaraldehyde-fixed pig pericardium + FET pre-incubated with human anti-Gal
      antibodies, calcification levels were significantly greater in alpha-Gal-positive
      pig pericardium (43.8 +/- 8.5 microg/mg) as compared with GT-KO pig pericardium
      (5.7 +/- 2.9 microg/mg) (p < 0.0001). CONCLUSIONS: This study demonstrates the
      role of alpha-Gal antigen and human alpha-Gal antibodies in the calcification
      process of valvular bioprostheses. It is suggested that GT-KO pig pericardium
      could be beneficial as a new source of material for heart valve bioprostheses.

PMID- 20036162
TI  - Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled
      hydrogen or carbon monoxide, or both.
AB  - BACKGROUND: Recent advances in novel medical gases, including hydrogen and carbon
      monoxide (CO), have demonstrated significant opportunities for therapeutic use.
      This study was designed to evaluate the effects of inhaled hydrogen or CO, or
      both, on cold ischemia/reperfusion (I/R) injury of the myocardium. METHODS:
      Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18
      hours of cold ischemia in Celsior solution. Survival, morphology, apoptosis and
      marker gene expression were assessed in the grafts after in vivo inhalation of
      hydrogen (1% to 3%), CO (50 to 250 ppm), both or neither. Both donors and
      recipients were treated for 1 hour before and 1 hour after reperfusion. RESULTS:
      After 6-hour cold ischemia, inhalation of hydrogen (>2%) or CO (250 ppm) alone
      attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in
      severe myocardial injury, and treatment with hydrogen or CO alone failed to
      demonstrate significant protection. Dual treatment with hydrogen and CO
      significantly attenuated I/R graft injury, reducing the infarcted area and
      decreasing in serum troponin I and creatine phosphokinase (CPK). Hydrogen
      treatment alone significantly reduced malondialdehyde levels and serum high
      mobility group box 1 protein levels as compared with air-treated controls. In
      contrast, CO only marginally prevented lipid peroxidation, but it suppressed I/R
      induced mRNA upregulation for several pro-inflammatory mediators and reduced
      graft apoptosis. CONCLUSIONS: Combined therapy with hydrogen and CO demonstrated
      enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory
      mechanisms, and may be a clinically feasible approach for preventing cold I/R
      injury of the myocardium.

PMID- 20036163
TI  - The change in heart allocation policy in the United States: is it working as
      designed?

PMID- 20036161
TI  - T-helper 2 cells are essential for modulation of vascular repair by allogeneic
      endothelial cells.
AB  - BACKGROUND: Endothelial cells (ECs) embedded within 3-dimensional matrices (MEEC)
      control lumenal inflammation and intimal hyperplasia when placed in the vascular
      adventitia. Matrix embedding alters endothelial immunogenicity in vitro. T-helper
      (Th) cell-driven host immunity is an impediment of allogeneic grafts. We aimed to
      identify if modulation of Th balance would affect immune compatibility and
      endothelial regulation of vascular repair in vivo. METHODS: Pigs (n = 4/group)
      underwent carotid artery balloon injury and were left untreated (Group 1) or
      received perivascular porcine MEEC implants (Group 2), 12 days of cyclosporine A
      (CsA; Group 3), or MEEC and CsA (Group 4). Host immune reactivity was analyzed
      after 28 and 90 days. RESULTS: MEEC treatment induced formation of EC-specific
      immunoglobulin (Ig) G(1) antibodies (41 +/- 6 mean fluorescence intensity [MFI])
      and differentiation of host splenocytes into Th2, but not Th1, cytokine-producing
      cells (interleukin [IL]-4, 242 +/- 102; IL-10, 273 +/- 114 number of spots).
      Concomitant CsA therapy reduced IgG(1) antibody frequency (25 +/- 2 MFI; p <
      0.02) and Th2-cytokine producing splenocytes upon MEEC treatment (IL-4, 157 +/-
      19; IL-10, 124 +/- 26 number of spots; p < 0.05). MEECs inhibited luminal
      occlusion 28 and 90 days after balloon injury (12 +/- 7%) vs untreated controls
      (68 +/- 14%; p < 0.001) but to a lesser extent with concomitant CsA treatment (34
      +/- 13%; p < 0.02 vs Group 2). CONCLUSIONS: MEECs do not induce a significant Th1
      driven immune response but do enhance differentiation of splenocytes into cells
      producing Th2 cytokine. Reduction in this Th2 response reduces the vasoregulatory
      effects of allogeneic ECs after injury.

PMID- 20036164
TI  - Excision of native heart and relocation of a grown heterotopic donor heart to the
      orthotopic position 14 years after transplantation.
AB  - Here we report the treatment of native heart complications (aortic regurgitation,
      ventricular fibrillation and heart failure) following a heterotopic heart
      transplant by excision of native heart and relocation the heterotopic heart in
      the orthotopic position. The patient was a 24 year old woman who had received a
      heterotopic transplant at the age of 9 years from a 9 year old donor. The donor
      heart had grown sufficiently to allow it to support her adult circulation.

PMID- 20036165
TI  - Upregulation of the apoptosis-related inflammasome in cardiac allograft
      rejection.
AB  - BACKGROUND: Inflammation is a major factor in cardiac allograft rejection.
      Accumulating reports have demonstrated an important role of the inflammation
      induced adaptor complex, called the inflammasome, in the field of immunology. The
      apoptosis-associated, speck-like protein containing a caspase recruitment domain
      (ASC) is an adaptor protein that forms the inflammasome and regulates caspase-1
      dependent generation of inflammatory cytokines. The aim of the present study was
      to determine how ASC is associated with the development of cardiac allograft
      rejection. METHODS: We used a murine heterotopic cardiac transplantation model
      between fully incompatible strains. Donor hearts (n = 9 for each time-point) were
      harvested for examination on Days 1, 4, 7 and 12 after transplantation.
      Histopathologic findings of cardiac grafts were evaluated using rejection scores.
      The expression of ASC and inflammatory cytokines in cardiac grafts were analyzed
      by immunohistochemistry and real-time reverse transcript-polymerase chain
      reaction (RT-PCR). RESULTS: Expression levels of both ASC and IL-1 beta were
      higher in the myocardial interstitium of allografts in parallel to the progress
      of cardiac rejection during the acute phase after transplantation. In contrast,
      expression of ASC and IL-1 beta remained low in isografts. Cardiac allografts
      treated with tacrolimus showed decreased expression of both ASC and IL-1 beta
      similar to that seen in isografts. Real-time RT-PCR demonstrated similar
      alteration of ASC and IL-1 beta mRNA expression in cardiac grafts during the
      acute phase. CONCLUSIONS: Our results demonstrate a novel finding showing that
      upregulation of ASC is closely associated with the inflammation induced in
      cardiac grafts after transplantation in the mouse.

PMID- 20036167
TI  - Seizure risk associated with neuroactive drugs: data from the WHO adverse drug
      reactions database.
AB  - PURPOSE: To explore the association between the use of neuroactive drugs and
      reports of epileptic seizures. MATERIAL: Using the WHO adverse drug reactions
      (ADR) database, VigiBase, we surveyed reports of suspected seizures from 1968
      until February 2006. Case reports of ADRs, that were classified as convulsions
      were collected and compared to the total number of ADRs reported. RESULTS: The
      total number of ADRs was 7,375,325. The number of convulsive events was 71,471.
      The ratio of convulsive ADRs to the total number of ADRs reported for each drug
      was evaluated and expressed as a percentage. The 10 drugs most frequently
      associated with convulsive ADRs were maprotilene (14.42%), escitaloprame (9.78%),
      buproprione (9.49%), clozapine (9.0%), chlorprothiexene (8.89%), amoxapine
      (8.74%), donepezil (8.40%), rivastigmine (6.41%), quetiapine (5.90%) and
      trimipramine (5.69%). CONCLUSIONS: Based on the reports in VigiBase, ADR reports
      relating to antidepressants, antipsychotic and cholinomimetic drugs included
      seizures more often than other neuroactive drugs.

PMID- 20036166
TI  - Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study.
AB  - PURPOSE: To determine the influence of epilepsy and its treatment on pregnancy
      and its outcome. DESIGN: Controlled, observational study. SETTING: National
      Health Service maternity hospitals in Liverpool and Manchester regions.
      POPULATION: 277 women with epilepsy (WWE) and 315 control women. METHODS: WWE
      were recruited from antenatal clinics. Controls were matched for age and parity
      but not gestational age. Information was obtained by interview and from clinical
      records. MAIN OUTCOME MEASURES: Obstetric complications, mode of delivery,
      condition of newborn. RESULTS: Distribution of epilepsy syndromes was similar to
      previous surveys. Most WWE (67%) received monotherapy with carbamazepine, sodium
      valproate or lamotrigine. Half WWE had no seizures during pregnancy but 34% had
      tonic clonic seizures. Seizure-related injuries were infrequent. Pregnancies with
      obstetric complications were increased in women with treated epilepsy (WWTE 45%,
      controls 33%; p=0.01). Most had normal vaginal delivery (WWTE 63%, controls 61%;
      p=0.65). Low birth weight was not increased (WWTE 6.2%, controls 5.2%; p=0.69).
      There were more major congenital malformations (MCM) (WWTE 6.6%, controls 2.1%;
      p=0.02) and fetal/infant deaths (WWTE 2.2%, controls 0.3%; p=0.09). Amongst
      monotherapies MCM prevalence was highest with valproate (11.3%; p=0.005).
      Lamotrigine (5.4%; p=0.23) and carbamazepine (3.0%; p=0.65) were closer to
      controls (2.1%). There was no association between MCM and dose of folic acid pre
      conception. CONCLUSION: MCM were more prevalent in the babies of WWTE
      particularly amongst those receiving sodium valproate.

PMID- 20036168
TI  - Factors defining care-seeking in low back pain--a meta-analysis of population
      based surveys.
AB  - Little is known about factors determining health care-seeking behavior in low
      back pain. While a number of studies have described general characteristics of
      health care utilization, only a few have aimed at appropriately assessing
      determinants of care-seeking in back pain, by comparing seekers and non-seekers.
      The objective of this systematic review was to identify determinants of health
      care-seeking in studies with well-defined groups of care-seekers and non-seekers
      with non-specific low back pain. A search was conducted in Medline, AMED, Cinahl,
      Web of Science, PsycINFO, National Research Register, Cochrane Library and LILACS
      looking for population- based surveys of non-specific low back pain patients
      older than 18 years, published since 1966. To be included in the review, studies
      needed to report on characteristics of well-defined groups of care-seekers and
      non-seekers. Methodological quality was assessed using a criteria list based on
      sampling, response rate, data reproducibility, power calculation and external
      validity. Risk estimates were expressed as odd ratios (95% confidence intervals).
      When possible, meta-analyses were performed, using a random effects model. Eleven
      studies were included in the review. Pooled results show that women are slightly
      more likely to seek care for their back pain as are patients with a previous
      history of back pain. Pain intensity was only slightly associated with care
      seeking, whereas patients with high levels of disability were nearly eight times
      more likely to seek care than patients with lower levels of disability.

PMID- 20036169
TI  - Self-discrepancies in work-related upper extremity pain: relation to emotions and
      flexible-goal adjustment.
AB  - Recurrent pain not only has an impact on disability, but on the long term it may
      become a threat to one's sense of self. This paper presents a cross-sectional
      study of patients with work-related upper extremity pain and focuses on: (1) the
      role of self-discrepancies in this group, (2) the associations between self
      discrepancies, pain, emotions and (3) the interaction between self-discrepancies
      and flexible-goal adjustment. Eighty-nine participants completed standardized
      self-report measures of pain intensity, pain duration, anxiety, depression and
      flexible-goal adjustment. A Selves Questionnaire was used to generate self
      discrepancies. A series of hierarchical regression analyses showed relationships
      between actual-ought other, actual-ought self, actual-feared self-discrepancies
      and depression as well as a significant association between actual-ought other
      self-discrepancy and anxiety. Furthermore, significant interactions were found
      between actual-ought other self-discrepancies and flexibility, indicating that
      less flexible participants with large self-discrepancies score higher on
      depression. This study showed that self-discrepancies are related to negative
      emotions and that flexible-goal adjustment served as a moderator in this
      relationship. The view of self in pain and flexible-goal adjustment should be
      considered as important variables in the process of chronic pain.

PMID- 20036170
TI  - Designing gradient coils with reduced hot spot temperatures.
AB  - Gradient coil temperature is an important concern in the design and construction
      of MRI scanners. Closely spaced gradient coil windings cause temperature hot
      spots within the system as a result of Ohmic heating associated with large
      current being driven through resistive material, and can strongly affect the
      performance of the coils. In this paper, a model is presented for predicting the
      spatial temperature distribution of a gradient coil, including the location and
      extent of temperature hot spots. Subsequently, a method is described for
      designing gradient coils with improved temperature distributions and reduced hot
      spot temperatures. Maximum temperature represents a non-linear constraint and a
      relaxed fixed point iteration routine is proposed to adjust coil windings
      iteratively to minimise this coil feature. Several examples are considered that
      assume different thermal material properties and cooling mechanisms for the
      gradient system. Coil winding solutions are obtained for all cases considered
      that display a considerable drop in hot spot temperature (>20%) when compared to
      standard minimum power gradient coils with equivalent gradient homogeneity,
      efficiency and inductance. The method is semi-analytical in nature and can be
      adapted easily to consider other non-linear constraints in the design of gradient
      coils or similar systems.

PMID- 20036171
TI  - Quantum mechanical calculations of the cephalosporin nucleus.
AB  - A computational study using several ab initio methods, HF, DFT and MP2 at
      different basis set levels (6-31G*, 6-31G**, 6-311G** and 6-311++G**) has been
      performed to determine the possible stable conformations attained by the
      cephalosporin nucleus. The calculations were carried out in three stages by
      studying the conformational analysis of the 3-cephem nucleus, the 3-cephem-4
      carboxylic acid nucleus and the acetylamino group of the 7-acetylamino-3cephem-4
      carboxylic acid. In the first two stages, the potential energy surfaces indicated
      two minima that correspond to the S1-up and C2-up conformations, with the S1-up
      being more stable. The energy required for the interconversion of the S1-up to
      the C2-up is around 7 kcal/mol, indicating the feasibility of interconversion
      between the two conformers. In the third stage, the acetylamino group attained
      two conformations with respect to the 3-cephem nucleus. All the geometric
      parameters obtained in this study were found to be in reasonably good agreement
      with available X-ray diffraction data, even upon using a simple basis set.

PMID- 20036172
TI  - Molecular docking study for the prediction of enantiodifferentiation of chiral
      styrene oxides by octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-gamma
      cyclodextrin.
AB  - A molecular docking study, using molecular mechanics calculations with AutoDock
      and semi-empirical PM3 calculations, was used to help predict the
      enantiodiscrimination of mono-substituted styrene oxides by octakis(2,3-di-O
      acetyl-6-O-tert-butyldimethylsilyl)-gamma-cyclodextrin (DIACTGCD), through the
      differences in the interaction energies and inclusion geometries. The small
      differences in the binding free energy values (DeltaDeltaG) obtained from
      AutoDock do not show any significant enantiodifferentiation, whereas structure re
      optimization with the PM3 algorithm results in larger binding energy differences
      (DeltaDeltaE). All DIACTGCD-styrene oxide inclusion complexes have binding
      energies in the range of -13.62 to -3.83 kcal mol(-1), indicating that the host
      guest interactions involved are hydrophobic and van der Waals forces between the
      C=O acetyl group, the O2/O3/O4 atoms of DIACTGCD and the substituents/epoxide
      group of styrene oxides. The effect of the same substituent position on the
      inclusion geometry is similar for all styrene oxides entirely embedded at or near
      the central DIACTGCD cavity. The degrees of enantiodiscrimination are: o>m>p for
      Cl-, CH(3)- and CF(3)-enantiomers and o>p>m for Br-, F- and NO(2)-enantiomers.
      The molecular docking results suggest that the complexation between styrene
      oxides and DIACTGCD depends on the type and position of the substituents on the
      aromatic ring. The high discriminatory ability exhibited by DIACTGCD against
      enantiomeric styrene oxides could potentially serve as a chiral selector, for
      example in chromatographic separation.

PMID- 20036173
TI  - Excited-state properties from ground-state DFT descriptors: A QSPR approach for
      dyes.
AB  - This work presents a quantitative structure-property relationship (QSPR)-based
      approach allowing an accurate prediction of the excited-state properties of
      organic dyes (anthraquinones and azobenzenes) from ground-state molecular
      descriptors, obtained within the (conceptual) density functional theory (DFT)
      framework. The ab initio computation of the descriptors was achieved at several
      levels of theory, so that the influence of the basis set size as well as of the
      modeling of environmental effects could be statistically quantified. It turns out
      that, for the entire data set, a statistically-robust four-variable multiple
      linear regression based on PCM-PBE0/6-31G calculations delivers a R(adj)(2) of
      0.93 associated to predictive errors allowing for rapid and efficient dye design.
      All the selected descriptors are independent of the dye's family, an advantage
      over previously designed QSPR schemes. On top of that, the obtained accuracy is
      comparable to the one of the today's reference methods while exceeding the one of
      hardness-based fittings. QSPR relationships specific to both families of dyes
      have also been built up. This work paves the way towards reliable and
      computationally affordable color design for organic dyes.

PMID- 20036175
TI  - Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase
      to a MPS VI patient with pachymeningitis cervicalis.
AB  - In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N
      acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and
      MPS VI patients often develop spinal cord compression during the course of the
      disease due to GAG storage within the cervical meninges, requiring neurosurgical
      intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not
      expected to cross the blood-brain barrier. We report the use of intrathecal (IT)
      recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in
      a MPS VI child with spinal cord compression whose parents initially refused the
      surgical treatment. Assessments were performed at baseline, with clinical,
      neurological and biochemical evaluations, urodynamic studies and MRI of the CNS.
      Changes on these parameters were evaluated after IT infusions of ASB administered
      monthly via lumbar puncture (LP) in a IV ERT naive patient. To our knowledge,
      this was the first MPS VI patient who received IT ERT. Despite significant
      urodynamic improvement and some neurological amelioration, the patient developed
      worsening of walking capacity. After IV ERT was started, the patient presented
      with a generalized hypotonia and a life-saving surgical fixation of the neck was
      then performed. The results observed on this MPS VI patient suggest that
      instability of the cervical vertebrae could be unmasked by IV ERT as joint
      storage is reduced, and the decrease in neck stiffness and stability could
      confound the expected improvement of SCC manifestations following IT ERT. The
      study of further patients, if possible in a clinical trial setting, is needed to
      evaluate the potential of a non-surgical IT ERT treatment of SCC for MPS VI.

PMID- 20036174
TI  - Coupling of the citrulline recycling to endothelial NO production.

PMID- 20036176
TI  - Viewing boxes: a survey in diagnostic radiology departments of Moroccan
      hospitals.
AB  - This work consists on a survey of the performance of viewing boxes installed in
      diagnostic radiology departments and included several aspects: checking the
      illuminance of the diagnostic rooms where the viewing boxes are located as well
      as the viewing boxes luminance levels and homogeneity. Seven hospitals took part
      in the survey, being three in the city of Casablanca and four in Rabat. A total
      of 136 viewing boxes and 18 diagnostic rooms have been checked. It was found that
      one diagnostic room works under normal conditions and that 80% of the viewing
      boxes present luminance levels below the international recommendations and the
      homogeneity is inadequate in 85%. Some simple and cheap initiatives can be
      performed in these departments to increase luminance and improve homogeneity
      levels such as cleaning and bulbs replacement.

PMID- 20036177
TI  - Advancement of high power ultrasound technology for the destruction of surface
      active waterborne contaminants.
AB  - The current paper explores recent advances in sonochemical techniques to improve
      the ultrasound-mediated degradation efficiency of surface active, waterborne
      contaminants. Sonochemical degradation efficiency of surface active contaminants
      generally has a strong dependence on the concentration of contaminant at the
      gas/solution surface of cavitation bubbles. This in turn depends on the
      thermodynamic and diffusion/kinetic-controlled adsorption properties of the
      surfactant at the rapidly pulsating gas/solution surface of acoustic cavitation
      bubbles. The adsorption properties of surfactants can be exploited to enhance
      their sonochemical decomposition by varying ultrasound exposure parameters such
      that changes in the nature of the bubble population (especially the bubble life
      time and rate of pulsations) cause changes in the amount of surfactant that
      adsorbs to the gas/solution interface of cavitation bubbles. Herein we describe
      recent results on the effect of ultrasound frequency and pulsing mode on
      sonochemical degradation of surfactants in aqueous solutions and show how the
      exposure parameters can be adjusted in ways to produce more efficient
      decomposition of contaminants, even under exposure conditions where seemingly
      poor sonochemical activity is detected in the bulk solution. The relevance of
      these results to scale-up of ultrasound decontamination processes is discussed.

PMID- 20036178
TI  - Biomechanical properties of the costovertebral joint.
AB  - Proper modeling of the human trunk requires a quantitative assessment of the
      stiffness of the costovertebral joints. Twelve samples (adjacent thoracic
      vertebrae and one rib segment) were harvested from three subjects. The ribs were
      loaded in the cranial-caudal direction, the ventral-dorsal direction and in
      torsion around the cervical rib axis. The force applied to and the displacement
      of the loading point on the rib were measured and used to determine the moment
      angle responses. Characteristic average curves and boundary curves containing the
      dataset were developed. The torsion response presented a range of motion--defined
      as the change in the angle for an applied moment varying from -0.1 to 0.1 Nm--of
      16.9+/-6.8 degrees which is more than three times the range in cranial-caudal
      flexion and five times the range in ventral-dorsal flexion. Statistical tests
      showed a significant difference between these ranges of motion. Significant inter
      subject variability was observed for the cranial-caudal flexion (p<0.05) while no
      intra-subject variability appeared. The characteristic moment-angle responses of
      the joints were well represented by third order polynomials (R(2)>0.9). This
      study expands and supplements the limited data available in the literature.
      Furthermore, it provides biomechanical data (closed-form moment-angle functions)
      that can be directly integrated into spine-ribcage models.

PMID- 20036179
TI  - ATP13A2 G2236A variant is rare in patients with early-onset Parkinson's disease
      and familial Parkinson's disease from Mainland China.

PMID- 20036180
TI  - Recognition of central sensitization in patients with musculoskeletal pain:
      Application of pain neurophysiology in manual therapy practice.
AB  - Central sensitization plays an important role in the pathophysiology of numerous
      musculoskeletal pain disorders, yet it remains unclear how manual therapists can
      recognize this condition. Therefore, mechanism based clinical guidelines for the
      recognition of central sensitization in patients with musculoskeletal pain are
      provided. By using our current understanding of central sensitization during the
      clinical assessment of patients with musculoskeletal pain, manual therapists can
      apply the science of nociceptive and pain processing neurophysiology to the
      practice of manual therapy. The diagnosis/assessment of central sensitization in
      individual patients with musculoskeletal pain is not straightforward, however
      manual therapists can use information obtained from the medical diagnosis,
      combined with the medical history of the patient, as well as the clinical
      examination and the analysis of the treatment response in order to recognize
      central sensitization. The clinical examination used to recognize central
      sensitization entails the distinction between primary and secondary hyperalgesia.

PMID- 20036181
TI  - Proline: a multifunctional amino acid.
AB  - Proline accumulates in many plant species in response to environmental stress.
      Although much is now known about proline metabolism, some aspects of its
      biological functions are still unclear. Here, we discuss the compartmentalization
      of proline biosynthesis, accumulation and degradation in the cytosol, chloroplast
      and mitochondria. We also describe the role of proline in cellular homeostasis,
      including redox balance and energy status. Proline can act as a signaling
      molecule to modulate mitochondrial functions, influence cell proliferation or
      cell death and trigger specific gene expression, which can be essential for plant
      recovery from stress. Although the regulation and function of proline
      accumulation are not yet completely understood, the engineering of proline
      metabolism could lead to new opportunities to improve plant tolerance of
      environmental stresses.

PMID- 20036182
TI  - Emerging principles in plant chemical genetics.
AB  - Chemical genetics is a powerful new discipline in plant science. Bioactive small
      molecules can be used to identify novel signalling nodes and unravel redundant
      networks. Observations made so far have revealed a series of principles in plant
      chemical genetics. These principles concern compound properties, such as
      bioactivation and bioavailability; and valuable approaches, like the use of
      derivatives and transcriptomics and successful ways of target identification.
      Together, these principles explain why the choice of the chemical library is
      important and instruct the design of future chemical genetic screens.

PMID- 20036183
TI  - Multi-enzymatic synthesis.
AB  - Biocatalytic conversions can involve one enzyme that carries out one specific
      reaction at a time, or multiple enzymes that carry out a series of conversions to
      yield a desired product. The use of several enzymes allows the realization of
      much more complex synthetic schemes. Multi-step synthesis can be carried out in
      biological systems by utilizing or engineering their metabolic networks for
      catalysis. Alternatively, multi-enzymatic catalysis can be carried out in vitro
      using isolated biocatalysts. Both approaches, in vivo or in vitro, have their
      specific advantages, problems, and challenges that will be illustrated using
      recent examples.

PMID- 20036185
TI  - Wolbachia: more than just a bug in insects genitals.
AB  - Research on the intracellular bacterial symbiont Wolbachia has grown on many
      levels, providing interesting insights on various aspects of the microbe's
      biology. Although data from fully sequenced genomes of different Wolbachia
      strains and from experimental studies of host-microbe interactions continue to
      arise, most of the molecular mechanisms employed by Wolbachia to manipulate the
      host cytoplasmic machinery and to ensure vertical transmission are yet to be
      discovered. Apart from the well-established role of Wolbachia in triggering
      reproductive alterations, a new fascinating aspect is emerging, related to the
      ecological benefits that the symbiont provides to the host. The mutualistic
      relationship of Wolbachia strains with disease vectors remains among the top
      research priorities with new insights having an impact on putative anti-filarial
      strategies.

PMID- 20036184
TI  - To catch a killer. What can mycobacterial models teach us about Mycobacterium
      tuberculosis pathogenesis?
AB  - Mycobacterium tuberculosis is the causative agent of the global tuberculosis
      epidemic. To combat this successful human pathogen we need a better understanding
      of the basic biology of mycobacterial pathogenesis. The use of mycobacterial
      model systems has the potential to greatly facilitate our understanding of how M.
      tuberculosis causes disease. Recently, studies using mycobacterial models,
      including M. bovis BCG, M. marinum, and M. smegmatis have significantly
      contributed to understanding M. tuberculosis. Specifically, there have been
      advances in genetic manipulation of M. tuberculosis using inducible promoters and
      recombineering that alleviate technical limitations in working with mycobacteria.
      Model systems have helped elucidate how secretion systems function at both the
      molecular level and during virulence. Mycobacterial models have also led to
      interesting hypotheses about how M. tuberculosis mediates latent infection and
      host response. While there is utility in using model systems to understand
      tuberculosis, each of these models represent distinct mycobacterial species with
      unique environmental adaptations. Directly comparing findings in model
      mycobacteria to those in M. tuberculosis will illuminate the similarities and
      differences between these species and increase our understanding of why M.
      tuberculosis is such a potent human pathogen.

PMID- 20036186
TI  - Spectral and physico-chemical investigations of novel homo-dinuclear di-micro2
      alkoxo bridged Schiff base complexes: 57Fe Mossbauer parameters of the Fe(III)
      complex.
AB  - Spectral and molecular model computations on homo-dinuclear complexes
      [M(2)L(2)(H(2)O)(2)Cl(2)] [L=1-(salicylaldeneamino)-3-hydroxypropane, M=Cr(3+),
      Mn(3+), Fe(3+), Co(3+), Ni(3+) or Cu(3+)] are consistent with a distorted hexa
      coordinate geometry. X-band EPR spectral data indicated a rhombic distortion
      around Cu(II) ion. Magnetic moment and (57)Fe Mossbauer data confirmed a high
      spin state electronic configuration (t(2g)(3)e(g)(2), S=5/2) and asymmetric
      ligand environment around Fe(III) with nuclear transitions Fe(+/-3/2-->1/2)
      exhibiting Kramer's double degeneracy. The neighboring Fe(III) nuclei in the homo
      dinuclear species are antiferromagnetically coupled.

PMID- 20036187
TI  - Synthesis, characterization and luminescence properties of Eu(III) and Tb(III)
      complexes with novel pyrazole derivatives and 1,10-phenanthroline.
AB  - Two novel pyrazole-derived ligands, 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1
      yl)picolinic acid (CDPA) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)-N
      phenylpicolinamide (CDPP) were prepared by 3,6-dichloropicolinic acid (DCPA).
      Their complexes with terbium(III) and europium(III) were synthesized. The
      complexes were characterized by elemental analysis, infrared spectra, (1)H NMR
      and TG-DTG. Furthermore, the above complexes using 1,10-phenanthroline as a
      secondary ligand were also synthesized and characterized. The luminescence
      properties of these complexes in solid state were investigated. The results
      suggested that Tb(III) complexes exhibit more efficient luminescence than Eu(III)
      complexes and the fluorescence of the complexes with 1,10-phenanthroline as a
      secondary ligand was prominently stronger than that of complexes without this
      ligand., and the three ligand (DCPA), (CDPP) and (CDPA) are excellent sensitizers
      to Eu(III) and Tb(III) ion.

PMID- 20036188
TI  - Vibrational spectra of two Fe(III)/EDTA complexes useful for iron
      supplementation.
AB  - The infrared and Raman spectra of Na[FeEDTA(H(2)O)]x2H(2)O and
      Na(4)[(FeEDTA)(2)O]x3H(2)O (EDTA=tetra anion of ethylenediaminetetraacetic acid),
      two complexes proposed as adequate for iron supplementation, were recorded and
      analyzed in relation to its structural peculiarities. Some comparisons between
      the recorded spectra are also presented, and the characteristics of the
      carboxylate motions as well as those of the metal-to-ligand vibrations are
      discussed in detail.

PMID- 20036189
TI  - Preparation and luminescence properties of lanthanide (Eu3+, Sm3+) complexes and
      their hectorite-based composites.
AB  - The complexes of europium and samarium with phthalates ligands were synthesized
      and characterized. The luminescence behaviors of the lanthanide complexes as well
      as their hectorite-based composites were investigated by fluorescence spectra.
      The results indicated that the lanthanide complexes showed slightly lower
      intensities in hectorite matrix than that of corresponding pure complexes. The
      lanthanide ion relative fluorescence intensity (LRFI) was enhanced when the
      lanthanide complexes were doped into hectorite.

PMID- 20036191
TI  - EPR and optical absorption studies of Cu2+ doped bis (glycinato) Mg (II)
      monohydrate single crystals.
AB  - Electron paramagnetic resonance (EPR) study of Cu(2+) doped bis (glycinato) Mg
      (II) monohydrate single crystals is carried out at room temperature. Copper
      enters the lattice substitutionally and is trapped at two magnetically
      inequivalent sites. The observed spectra are fitted to a spin-Hamiltonian of
      rhombic symmetry with the following values of the parameters: Cu(2+) (I),
      g(x)=2.1577+/-0.0002, g(y)=2.2018+/-0.0002, g(z)=2.3259+/-0.0002, A(x)=(87+/
      2)x10(-4)cm(-1), A(y)=(107+/-2)x10(-4)cm(-1), A(z)=(141+/-2)x10(-4)cm(-1); Cu
      (2+) (II), g(x)=2.1108+/-0.0002, g(y)=2.1622+/-0.0002, g(z)=2.2971+/-0.0002,
      A(x)=(69+/-2)x10(-4)cm(-1), A(y)=(117+/-2)x10(-4)cm(-1)and A(z)=(134+/-2)x10(
      4)cm(-1). The ground state wave function of the Cu(2+) ion in this lattice is
      evaluated to be predominantly |x(2)-y(2). The g-factor anisotropy is also
      calculated and compared with the experimental value. With the help of the optical
      absorption study, the nature of bonding in the complex is discussed.

PMID- 20036190
TI  - Infrared spectroscopic and DFT investigations of the vanadate-tellurate glasses
      structures.
AB  - Vanadate-tellurate vitreous systems with composition (1-x)TeO(2).xV(2)O(5) where
      x=0.3 and 0.4 have been prepared by the conventional melt-quench method. The
      structural aspects have been investigated using FTIR spectroscopy and the density
      functional theory (DFT) calculations. The present study provides the interesting
      information concerning devitrification behavior of the vanadate-tellurate
      vitreous system which occur Te(2)V(2)O(9) crystalline phase. The structure of the
      heat-treated glasses was found to consist mainly of rings containing [TeO(3)],
      [TeO(4)], [VO(4)] and some [VO(5)] structural units.

PMID- 20036192
TI  - Synthesis, characterization, molecular modeling and antimicrobial activity of 2
      (2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N-phenylacetamide copper complexes.
AB  - Six Cu(II) complexes of 2-(2-(ethylcarbamothioyl)hydrazinyl)-2-oxo-N
      phenylacetamide (H(3)APET) have been prepared and characterized by elemental
      analyses, spectral (IR, UV-vis, (1)H NMR and ESR) as well as magnetic and thermal
      measurements. The data revealed that the ligand acts as ON bidentate, ONS
      tridentate or ONNS tetradentate forming structure in which each copper atom is a
      tetrahedral or tetragonal environment. The bond length, bond angle, HOMO, LUMO,
      dipole moment and charges on the atoms have been calculated to confirm the
      geometry of the ligand and the investigated complexes. Kinetic parameters were
      determined for each thermal degradation stage of the Cu(II) complexes using Coats
      Redfern and Horowitz-Metzger methods. Moreover, the ligand and its complexes were
      screened against bacteria Staphylococcus aureus, Escherichia coli, Candida and
      fungi, Albicans and Aspergillus flavus using the inhibitory zone diameter.

PMID- 20036193
TI  - Creation and evaluation of EMR-based paper clinical summaries to support HIV-care
      in Uganda, Africa.
AB  - PURPOSE: Getting the right information to providers can improve quality of care.
      We set out to provide patient-specific Electronic Medical Record (EMR)-based
      clinical summaries for providers taking care of HIV-positive adult patients in
      the resource-limited setting of Mbarara, Uganda. METHODS: We evaluated the impact
      of implementing these clinical summaries using time-motion techniques and
      provider surveys. RESULTS: After implementation of EMR-based clinical summaries,
      providers spent more time in direct care of patients (2.9 min vs. 2.3 min,
      p<0.001), and the length of patient visits was reduced by 11.5 min. Survey
      respondents indicated that clinical summaries improved care, reduced mistakes,
      and were generally accurate. Current antiretroviral medication, patient
      identifying information, adherence information, current medication, and current
      medical problems were among the highest-rated elements of the summary.
      CONCLUSIONS: By taking advantage of data stored in EMRs, efficiency and quality
      of care can be improved through clinical summaries, even in settings with limited
      resources.

PMID- 20036195
TI  - IGF-1R targeted treatment of sarcoma.

PMID- 20036194
TI  - Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody
      figitumumab (CP-751,871) in patients with sarcoma and Ewing's sarcoma: a phase 1
      expansion cohort study.
AB  - BACKGROUND: Figitumumab is a fully human IgG2 monoclonal antibody targeting the
      insulin-like growth-factor-1 receptor (IGF-1R). Preclinical data suggest a
      dependence on insulin-like growth-factor signalling for sarcoma subtypes,
      including Ewing's sarcoma, and early reports show antitumour activity of IGF-1R
      targeting drugs in these diseases. METHODS: Between January, 2006, and August,
      2008, patients with refractory, advanced sarcomas received figitumumab (20 mg/kg)
      in two single-stage expansion cohorts within a solid-tumour phase 1 trial. The
      first cohort (n=15) included patients with multiple sarcoma subtypes, age 18
      years or older, and the second cohort (n=14) consisted of patients with
      refractory Ewing's sarcoma, age 9 years or older. The primary endpoint was to
      assess the safety and tolerability of figitumumab. Secondary endpoints included
      pharmacokinetic profiling and preliminary antitumour activity (best response by
      Response Evaluation Criteria in Solid Tumours [RECIST]) in evaluable patients who
      received at least one dose of medication. This study is registered with
      ClinicalTrials.gov, number NCT00474760. FINDINGS: 29 patients, 16 of whom had
      Ewing's sarcoma, were enrolled and received a total of 177 cycles of treatment
      (median 2, mean 6.1, range 1-24). Grade 3 deep venous thrombosis, grade 3 back
      pain, and grade 3 vomiting were each noted once in individual patients; one
      patient had grade 3 increases in aspartate aminotransferase and
      gammaglutamyltransferase concentrations. This patient also had grade 4 increases
      in alanine aminotransferase concentrations. The only other grade 4 adverse event
      was raised concentrations of uric acid, noted in one patient. Pharmacokinetics
      were comparable between patients with sarcoma and those with other solid tumours.
      28 patients were assessed for response; two patients, both with Ewing's sarcoma,
      had objective responses (one complete response and one partial response) and
      eight patients had disease stabilisation (six with Ewing's sarcoma, one with
      synovial sarcoma, and one with fibrosarcoma) lasting 4 months or longer.
      INTERPRETATION: Figitumumab is well tolerated and has antitumour activity in
      Ewing's sarcoma, warranting further investigation in this disease. FUNDING:
      Pfizer Global Research and Development.

PMID- 20036196
TI  - Pathogenesis of Parkinson's disease: emerging role of molecular chaperones.
AB  - Several neurodegenerative diseases, including Parkinson's disease (PD) are
      associated with protein misfolding and the formation of distinct aggregates,
      resulting in a putative pathological protein load on the nervous system. A
      variety of factors cause proteins to aggregate, including aggregation-prone
      sequences, specific mutations, protein modifications and also dysregulation of
      the protein degradation machinery. Molecular chaperones are responsible for
      maintaining normal protein homeostasis within the cell by assisting protein
      folding and modulating protein-degrading pathways. Here, we review the
      fundamental mechanisms of neurodegeneration occurring in PD involving alpha
      synuclein fibrillisation and aggregation, endoplasmic reticulum stress, ubiquitin
      proteasome systems, autophagy and lysosomal degradation. Molecular chaperones
      serve a neuroprotective role in many of these pathways, and we discuss recent
      evidence indicating that these proteins might provide the basis for new
      therapeutic approaches.

PMID- 20036197
TI  - Elongator - an emerging role in neurological disorders.
AB  - Neurological disorders are becoming a major public health issue in our aging
      society. An important objective is to understand the molecular events that
      underlie these diseases to prevent their onset and/or halt their progression.
      Acetylation of alpha-tubulin is a post-translational modification of microtubules
      that serves as a recognition signal for the anchoring of molecular motors and, as
      such, underlies the transport of various proteins or organelles in neurons. This
      process is affected in striatal and cortical neurons from Huntington's disease
      patients. Recent studies have shown that Elp3, the catalytic subunit of the
      Elongator complex, promotes the acetylation of alpha-tubulin in microtubules.
      Elongator complex activity is impaired in patients with familial dysautonomia.
      Based on converging experimental and clinical evidence, we propose that Elongator
      might be commonly targeted in different neurological disorders, and thus might
      represent a strong candidate for research and development efforts to design drug
      based therapies.

PMID- 20036198
TI  - How should we evaluate a new technique in a constantly changing world? The Pace
      and Ablate study.

PMID- 20036199
TI  - Circumferential pulmonary vein isolation and linear left atrial ablation as a
      single-catheter technique to achieve bidirectional conduction block: the pace-and
      ablate approach.
AB  - BACKGROUND: Pulmonary vein (PV) isolation has become a cornerstone for ablation
      of atrial fibrillation (AF). Circular mapping catheter (CMC)-guided techniques
      for detection of lesion gaps are challenging. OBJECTIVE: The present study
      describes a new concept of circumferential PV ablation aiming at bidirectional
      conduction block based on simultaneous pacing and ablation through the tip of a
      single mapping/ablation catheter. METHODS: A total of 147 patients with AF
      received circumferential PV ablation. In persistent AF, a posterior "box" lesion
      and a mitral isthmus line were added. All procedures were performed in sinus
      rhythm. Gaps within the left atrial (LA) ablation lines were detected and closed
      using voltage and pace mapping through the mapping/ablation catheter.
      Bidirectional conduction block was the procedural end point. Subsequently, the
      end point was validated by an independent electrophysiologist using a CMC.
      RESULTS: Procedural and radiation time measured 188 +/- 55 and 37 +/- 15 min.
      Bidirectional PV conduction block (lack of PV potentials and lack of LA capture)
      was found in 140 of 147 (95%) patients with single mapping/ablation catheter and
      in 138 of 147 (94%) patients with CMC. Early PV reconduction was seen in 22 of
      147 (15%) patients. After 12 months follow-up, 84% of the patients were free from
      AF and/or atrial macro-re-entrant tachycardia. The rate of reablations was 10%
      and 24% for patients with paroxysmal and persistent AF, respectively. CONCLUSION:
      Pacing and ablation from the tip of the mapping/ablation catheter is feasible to
      detect and close gaps within long atrial ablation lines to consistently achieve
      bidirectional conduction block.

PMID- 20036200
TI  - Caenorhabditis elegans APN-1 plays a vital role in maintaining genome stability.
AB  - We previously showed that Caenorhabditis elegans APN-1, the only metazoan
      apurinic/apyrimidinc (AP) endonuclease belonging to the endonuclease IV family,
      can functionally rescue the DNA repair defects of Saccharomyces cerevisiae
      mutants completely lacking AP endonuclease/3'-diesterase activities. While this
      complementation study provided the first evidence that APN-1 possesses the
      ability to act on DNA lesions that are processed by AP endonucleases/3'
      diesterase activities, no former studies were conducted to examine its biological
      importance in vivo. Herein, we show that C. elegans knockdown for apn-1 by RNAi
      displayed phenotypes that are directly linked with a defect in maintaining the
      integrity of the genome. apn-1(RNAi) animals exhibited a 5-fold increase in the
      frequency of mutations at a gfp-lacZ reporter and showed sensitivities to DNA
      damaging agents such as methyl methane sulfonate and hydrogen peroxide that
      produce AP site lesions and strand breaks with blocked 3'-ends. The apn-1(RNAi)
      worms also displayed a delay in the division of the P1 blastomere, a defect that
      is consistent with the accumulation of unrepaired lesions. Longevity was only
      compromised, if the apn-1(RNAi) animals were challenged with the DNA damaging
      agents. We showed that apn-1(RNAi) knockdown suppressed formation of apoptotic
      corpses in the germline caused by an overburden of AP sites generated from uracil
      DNA glycosylase mediated removal of misincorporated uracil. Finally, we showed
      that depletion of APN-1 by RNAi partially rescued the lethality resulting from
      uracil misincorporation, suggesting that APN-1 is an important AP endonuclease
      for repair of misincorporated uracil.

PMID- 20036201
TI  - Metabolomic analysis of uremic toxins by liquid chromatography/electrospray
      ionization-tandem mass spectrometry.
AB  - We applied the metabolomic analysis of comprehensive small-molecular metabolites
      using liquid chromatography/electrospray ionization-tandem mass spectrometry
      (LC/ESI-MS/MS) and principal component analysis to identify uremic toxins
      accumulated in the serum of chronic renal failure (CRF) rats. CRF rats were
      produced by 5/6-nephrectomy. Indoxyl sulfate was demonstrated to be the first
      principal serum metabolite which differentiates CRF from normal, followed by
      phenyl sulfate, hippuric acid and p-cresyl sulfate. Then, we measured the serum
      levels of indoxyl sulfate, phenyl sulfate, hippuric acid and p-cresyl sulfate by
      the selected reaction monitoring (SRM) of LC/ESI-MS/MS, and demonstrated that
      these serum levels were markedly increased in CRF rats as compared with normal
      rats. As creatinine clearance decreased, the serum levels of the metabolites
      increased.

PMID- 20036202
TI  - Gender variation in oesophageal motor function: analysis of 129 healthy
      individuals.
AB  - BACKGROUND: Oesophageal manometry is the standard for diagnosis of oesophageal
      motor disorders. Minimal data exist assessing the effect of gender on normal
      oesophageal manometry values. AIM: Evaluate the impact of gender on normal
      oesophageal manometry values. METHODS: Healthy volunteers were recruited from the
      Jacksonville metropolitan area. Exclusion criteria were symptoms suggestive of
      oesophageal disease, medication use or concurrent illness that could affect
      oesophageal manometry. All underwent oesophageal manometry using a solid-state
      system with wet swallows. RESULTS: Sixty-three males and 66 females were
      enrolled. All completed oesophageal manometry without difficulty. Resting lower
      oesophageal sphincter pressure, distal oesophageal contraction duration and
      distal oesophageal body contraction amplitude values were significantly higher in
      females while distal oesophageal body contraction velocity was significantly
      lower in females (p<0.05). No differences were seen in other oesophageal
      manometry parameters. CONCLUSION: Significant gender differences exist in normal
      oesophageal manometry. Gender-specific reference values for oesophageal manometry
      are needed for accurate diagnosis of oesophageal motility disorders.

PMID- 20036203
TI  - The diagnostic value of the duodenal biopsy: a clinico-pathologic analysis of
      28,000 patients.
AB  - BACKGROUND: Duodenal biopsies are frequently obtained to investigate
      malabsorption, diarrhoea, and anemia. The proportion of patients who have
      duodenal biopsies and their diagnostic yield are unclear. AIMS: To determine what
      proportion of patients undergoing esophagogastroduodenoscopy in a private setting
      has duodenal biopsies and to evaluate the diagnostic yield relative to clinical
      indications and endoscopic findings. METHODS: Records of patients who had
      duodenal biopsies diagnosed at a United States gastrointestinal pathology
      laboratory in a single year were analysed. RESULTS: 28,210 patients with and
      75,175 without duodenal biopsies were studied. Duodenal biopsy patients were
      younger (52 years versus 58 years, p<0.001) and more likely to be female (OR
      1.46; p<0.0001); 87% of children and 27% of adults had duodenal biopsies.
      Suspicion of malabsorption or sprue, diarrhoea, anemia, and weight loss were
      strong predictors of duodenal biopsy. More than 80% of patients had normal
      duodenum, except those biopsied for sprue, 64% of whom had normal findings. Marsh
      II-IIIc lesions were diagnosed in 23% of patients with suspected sprue, but in
      3.0% of those with diarrhoea, weight loss, or anemia, and in 1.5% of patients
      with dyspepsia or GERD. CONCLUSIONS: A clinical suspicion of sprue produces the
      highest yield of histopathologic abnormalities; women are biopsied more often
      than men despite having less duodenal pathology.

PMID- 20036204
TI  - Obstructive jaundice due to primary neurofibroma of the common bile duct.

PMID- 20036205
TI  - Chronic abscess formation following mesh mastopexy: case report.
AB  - Mastopexy is a challenging procedure that relies on the redistribution of breast
      parenchyma and tightening of the skin envelope to provide long-lasting correction
      of ptosis. Recurrent ptosis, however, is an inevitable complication of many
      techniques and internal parenchymal supports using autologous or non-autologous
      material have been tried in an attempt to counteract the effects of gravity.
      Several studies have reported good long-term outcomes using synthetic mesh with a
      low rate of complications, however concerns remain including foreign body
      reaction, infection, and oncological surveillance. This article reports a case of
      chronic breast abscess formation following the use of polypropylene mesh in
      mastopexy and the radiological and operative findings.

PMID- 20036206
TI  - Real-time assay method of lipid extraction activity.
AB  - Intracellular lipid translocation is mediated by lipid transfer proteins and
      their functional impairments cause severe disorder in lipid metabolism. However,
      molecular mechanisms of protein-mediated lipid transfer remain unclear since
      conventional assay methods could not observe elementary processes in the lipid
      transfer reaction, such as lipid bilayer binding and lipid uptake. In this study,
      we found that ceramide extraction mediated by a ceramide trafficking protein
      (CERT) could be detected as decreasing the response of surface plasmon resonance
      (SPR). Based on this finding, we developed a novel real-time assay method that
      enables quantitative evaluation of the ceramide extraction activity of CERT,
      using the SPR technique. Performing this SPR-based assay using ceramide-embedded
      and ceramide-free lipid bilayers as ligands allows for the exclusive
      investigation of ceramide uptake processes, differentiating them from other CERT
      membrane binding events. Furthermore, mutagenesis experiments of CERT using this
      SPR-based assay clearly elucidated whether an amino acid residue plays a role in
      the ceramide uptake process or the lipid bilayer binding process. This SPR-based
      assay method can separately evaluate the lipid extraction activity and lipid
      bilayer binding activity of the lipid transfer proteins, and provide more
      detailed information about lipid transfer phenomena.

PMID- 20036208
TI  - Detection of microarray-hybridized oligonucleotides with magnetic beads.
AB  - The efficiency of hybridization analysis with oligonucleotide microarrays depends
      heavily on the method of detection. Conventional methods based on labeling
      nucleic acids with fluorescent, chemiluminescent, enzyme, or radioactive
      reporters suffer from a number of serious drawbacks which demand development of
      new detection techniques. Here, we report two new approaches for detection of
      hybridization with oligonucleotide microarrays employing magnetic beads as active
      labels. In the first method streptavidin-coated magnetic beads are used to
      discover biotin-labeled DNA molecules hybridized with arrayed oligonucleotide
      probes. In the second method biotin-labeled DNA molecules are bound first to the
      surface of magnetic beads and then hybridized with arrayed complementary strands
      on bead-array contacts. Using a simple low-power microscope with a dark-field
      illumination and a pair of complementary primers as a model hybridization system
      we evaluated sensitivity, speed, and cost of the new detection method and
      compared its performance with the detection techniques employing enzyme and
      fluorescent labels. It was shown that the detection of microarray-hybridized DNA
      with magnetic beads combines low cost with high speed and enhanced assay
      sensitivity, opening a new way to routine hybridization assays which do not
      require precise measurements of DNA concentration.

PMID- 20036207
TI  - Hexahistidine-tag-specific optical probes for analyses of proteins and their
      interactions.
AB  - The hexahistidine (His(6))/nickel(II)-nitrilotriacetic acid (Ni(2+)-NTA) system
      is widely used for affinity purification of recombinant proteins. The NTA group
      has many other applications, including the attachment of chromophores,
      fluorophores, or nanogold to His(6) proteins. Here we explore several
      applications of the NTA derivative, (Ni(2+)-NTA)(2)-Cy3. This molecule binds our
      two model His(6) proteins, N-ethylmaleimide sensitive factor (NSF) and O(6)
      alklyguanine-DNA alkyltransferase (AGT), with moderate affinity (K approximately
      1.5 x 10(6) M(-1)) and no effect on their activity. Its high specificity makes
      (Ni(2+)-NTA)(2)-Cy3 ideal for detecting His(6) proteins in complex mixtures of
      other proteins, allowing (Ni(2+)-NTA)(2)-Cy3 to be used as a probe in crude cell
      extracts and as a His(6)-specific gel stain. (Ni(2+)-NTA)(2)-Cy3 binding is
      reversible in 10mM ethylenediaminetetraacetic acid (EDTA) or 500 mM imidazole,
      but in their absence it exchanges slowly (k(exchange) approximately 5 x 10(-6) s(
      1) with 0.2 microM labeled protein in the presence of 1 microM His(6) peptide).
      Labeling with (Ni(2+)-NTA)(2)-Cy3 allows characterization of hydrodynamic
      properties by fluorescence anisotropy or analytical ultracentrifugation under
      conditions that prevent direct detection of protein (e.g., high ADP absorbance).
      In addition, fluorescence resonance energy transfer (FRET) between (Ni(2+)
      NTA)(2)-Cy3-labeled proteins and suitable donors/acceptors provides a convenient
      assay for binding interactions and for measurements of donor-acceptor distances.

PMID- 20036209
TI  - Normalizing genes for real-time polymerase chain reaction in epithelial and
      nonepithelial cells of mouse small intestine.
AB  - Gene expression studies in intestinal epithelial and stromal cells are a common
      tool for investigating the mechanisms by which the homeostasis of the small
      intestine is regulated under normal and pathological conditions. Quantitative
      real-time PCR (qPCR) is a sensitive and highly reproducible method of gene
      expression analysis, with expression levels quantified by normalization against
      reference genes in most cases. However, the lack of suitable reference genes for
      epithelial cells with different differentiation states and nonepithelial tissue
      cells has limited the application of qPCR in gene expression studies of small
      intestinal samples. In this study, 13 housekeeping genes, ACTB, B2M, GAPDH, GUSB,
      HPRT1, HMBS, HSP90AB1, RPL13A, RPS29, RPLP0,PPIA, TBP, and TUBA1, were analyzed
      to determine their applicability for isolated crypt cells, villus cells,
      deepithelialized mucosa, and whole mucosa of the mouse small intestine. Using
      geNorm and NormFinder software, GUSB and TBP were identified as the most stably
      expressed genes, whereas the expressions of the commonly used reference genes
      GAPDH, B2M, and ACTB, and ribosomal protein genes RPL13A, RPS29, and RPLP0 were
      relatively unstable. Thus, this study demonstrates that GUSB and TBP are the
      optimal reference genes for the normalization of gene expression in the mouse
      small intestine.

PMID- 20036210
TI  - Non-natural amino acid fluorophores for one- and two-step fluorescence resonance
      energy transfer applications.
AB  - Fluorescence resonance energy transfer (FRET) provides a powerful means to study
      protein conformational changes. However, the incorporation of an exogenous FRET
      pair into a protein could lead to undesirable structural perturbations of the
      native fold. One of the viable strategies to minimizing such perturbations is to
      use non-natural amino acid-based FRET pairs. Previously, we showed that p
      cyanophenylalanine (Phe(CN)) and tryptophan (Trp) constitute such a FRET pair,
      useful for monitoring protein folding-unfolding transitions. Here we further show
      that 7-azatryptophan (7AW) and 5-hydroxytryptophan (5HW) can also serve as a FRET
      acceptor to Phe(CN), and the resultant FRET pairs offer certain advantages over
      Phe(CN)-Trp. For example, the fluorescence spectrum of 7AW is sufficiently
      separated from that of Phe(CN), making it straightforward to decompose the FRET
      spectrum into donor and acceptor contributions. Moreover, we show that Phe(CN),
      Trp, and 7AW can be used together to form a multi-FRET system, allowing more
      structural information to be extracted from a single FRET experiment. The
      applicability of these FRET systems is demonstrated in a series of studies where
      they are employed to monitor the urea-induced unfolding transitions of the villin
      headpiece subdomain (HP35), a designed betabetaalpha motif (BBA5), and the human
      Pin1 WW domain.

PMID- 20036211
TI  - Excitation energy transfer to Photosystem I in filaments and heterocysts of
      Nostoc punctiforme.
AB  - Cyanobacteria adapt to varying light conditions by controlling the amount of
      excitation energy to the photosystems. On the minute time scale this leads to
      redirection of the excitation energy, usually referred to as state transitions,
      which involves movement of the phycobilisomes. We have studied short-term light
      adaptation in isolated heterocysts and intact filaments from the cyanobacterium
      Nostoc punctiforme ATCC 29133. In N. punctiforme vegetative cells differentiate
      into heterocysts where nitrogen fixation takes place. Photosystem II is
      inactivated in the heterocysts, and the abundancy of Photosystem I is increased
      relative to the vegetative cells. To study light-induced changes in energy
      transfer to Photosystem I, pre-illumination was made to dark adapted isolated
      heterocysts. Illumination wavelengths were chosen to excite Photosystem I (708nm)
      or phycobilisomes (560nm) specifically. In heterocysts that were pre-illuminated
      at 708nm, fluorescence from the phycobilisome terminal emitter was observed in
      the 77K emission spectrum. However, illumination with 560nm light caused
      quenching of the emission from the terminal emitter, with a simultaneous increase
      in the emission at 750nm, indicating that the 560nm pre-illumination caused
      trimerization of Photosystem I. Excitation spectra showed that 560nm pre
      illumination led to an increase in excitation transfer from the phycobilisomes to
      trimeric Photosystem I. Illumination at 708nm did not lead to increased energy
      transfer from the phycobilisome to Photosystem I compared to dark adapted
      samples. The measurements were repeated using intact filaments containing
      vegetative cells, and found to give very similar results as the heterocysts. This
      demonstrates that molecular events leading to increased excitation energy
      transfer to Photosystem I, including trimerization, are independent of
      Photosystem II activity.

PMID- 20036212
TI  - Structure and function of mitochondrial supercomplexes.
AB  - The five complexes (complexes I-V) of the oxidative phosphorylation (OXPHOS)
      system of mitochondria can be extracted in the form of active supercomplexes.
      Single-particle electron microscopy has provided 2D and 3D data describing the
      interaction between complexes I and III, among I, III and IV and in a dimeric
      form of complex V, between two ATP synthase monomers. The stable interactions are
      called supercomplexes which also form higher-ordered oligomers. Cryo-electron
      tomography provides new insights on how these supercomplexes are arranged within
      intact mitochondria. The structure and function of OXPHOS supercomplexes are
      discussed.

PMID- 20036213
TI  - RNA and DNA interactions with zwitterionic and charged lipid membranes - a DSC
      and QCM-D study.
AB  - The aim of the present study is to establish under which conditions tRNA
      associates with phospholipid bilayers, and to explore how this interaction
      influences the lipid bilayer. For this purpose we have studied the association of
      tRNA or DNA of different sizes and degrees of base pairing with a set of model
      membrane systems with varying charge densities, composed of zwitterionic
      phosphatidylcholines (PC) in mixtures with anionic phosphatidylserine (PS) or
      cationic dioctadecyl-dimethyl-ammoniumbromide (DODAB), and with fluid or solid
      acyl-chains (oleoyl, myristoyl and palmitoyl). To prove and quantify the
      attractive interaction between tRNA and model-lipid membrane we used quartz
      crystal microbalance with dissipation (QCM-D) monitoring to study the tRNA
      adsorption to deposit phospholipid bilayers from solutions containing monovalent
      (Na(+)) or divalent (Ca(2+)) cations. The influence of the adsorbed polynucleic
      acids on the lipid phase transitions and lipid segregation was studied by means
      of differential scanning calorimetry (DSC). The basic findings are: i) tRNA
      adsorbs to zwitterionic liquid-crystalline and gel-phase phospholipid bilayers.
      The interaction is weak and reversible, and cannot be explained only on the basis
      of electrostatic attraction. ii) The adsorbed amount of tRNA is higher for liquid
      crystalline bilayers compared to gel-phase bilayers, while the presence of
      divalent cations show no significant effect on the tRNA adsorption. iii) The
      adsorption of tRNA can lead to segregation in the mixed 1,2-dimyristoyl-sn
      glycerol-3-phosphatidylcholine (DMPC)-1,2-dimyristoyl-sn-glycero-3
      phosphatidylserine (DMPS) and DMPC-DODAB bilayers, where tRNA is likely excluded
      from the anionic DMPS-rich domains in the first system, and associated with the
      cationic DODAB-rich domains in the second system. iv) The addition of shorter
      polynucleic acids influence the chain melting transition and induce segregation
      in a mixed DMPC-DMPS system, while larger polynucleic acids do not influence the
      melting transition in these system. The results in this study on tRNA
      phospholipid interactions can have implications for understanding its biological
      function in, e.g., the cell nuclei, as well as in applications in biotechnology
      and medicine.

PMID- 20036214
TI  - Sphingosine-1-phosphate receptor S1P1 is regulated by direct interactions with P
      Rex1, a Rac guanine nucleotide exchange factor.
AB  - Sphingosine-1-phosphate (S1P) receptors S1P(1) are emerging molecular targets for
      the treatment of cancer, vascular and immune diseases, due to their pivotal role
      in cell migration and survival of immune and endothelial cells. A therapeutic
      strategy to control S1P(1) function is based on agonists that promote changes on
      S1P(1) expression at the plasma membrane. Here, we explored the hypothesis that
      cell surface expression and function of S1P(1) are influenced by direct
      interactions with P-Rex1, a guanine nucleotide exchange factor for Rac. We
      demonstrate that P-Rex1-PDZ domains interact with S1P(1)-carboxyl terminal tail
      and full length receptor monomers and dimers. Endothelial cells transfected with
      P-Rex1-PDZ domains show an increased migratory response to S1P. S1P(1)
      trafficking to intracellular compartments is diminished by coexpression of P
      Rex1. We conclude that S1P(1) signaling linked to cell migration is facilitated
      by a functional interaction with P-Rex1 via a mechanism that involves the
      maintenance of S1P(1) receptors at the cell membrane.

PMID- 20036215
TI  - Protein location prediction using atomic composition and global features of the
      amino acid sequence.
AB  - Subcellular location of protein is constructive information in determining its
      function, screening for drug candidates, vaccine design, annotation of gene
      products and in selecting relevant proteins for further studies. Computational
      prediction of subcellular localization deals with predicting the location of a
      protein from its amino acid sequence. For a computational localization prediction
      method to be more accurate, it should exploit all possible relevant biological
      features that contribute to the subcellular localization. In this work, we
      extracted the biological features from the full length protein sequence to
      incorporate more biological information. A new biological feature, distribution
      of atomic composition is effectively used with, multiple physiochemical
      properties, amino acid composition, three part amino acid composition, and
      sequence similarity for predicting the subcellular location of the protein.
      Support Vector Machines are designed for four modules and prediction is made by a
      weighted voting system. Our system makes prediction with an accuracy of 100,
      82.47, 88.81 for self-consistency test, jackknife test and independent data test
      respectively. Our results provide evidence that the prediction based on the
      biological features derived from the full length amino acid sequence gives better
      accuracy than those derived from N-terminal alone. Considering the features as a
      distribution within the entire sequence will bring out underlying property
      distribution to a greater detail to enhance the prediction accuracy.

PMID- 20036216
TI  - Ischemia-activated microglia induces neuronal injury via activation of gp91phox
      NADPH oxidase.
AB  - Although glial cells play a major role in the pathogenesis of many neurological
      diseases by exacerbating neuronal and non-neuronal cell death, the mechanisms
      involved are unclear. We examined the effects of microglia-(MCM) or astrocyte
      (ACM) conditioned media obtained by chemical ischemia on the neuronal injury in
      SH-SY5Y cells. Chemical ischemia was induced by the treatment with NaN(3) and 2
      deoxy-d-glucose for 2h. MCM-treated SH-SY5Y cells showed reduced the viability,
      increased caspase-3 activity, decreased Bcl-2/Bax ratio, and increased cytochrome
      c release, increased inflammatory cytokines, and increased reactive oxygen
      species (ROS) generation. MCM also increased gp91phox nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase, which was inhibited by NADPH oxidase
      inhibitor, apocynin, and gp91phox siRNA. However, ACM did not show any
      significant changes. The results suggest that microglia activated by ischemic
      insult may increase reactive oxygen species generation via activation of gp91phox
      NADPH oxidase, resulting in neuronal injury.

PMID- 20036217
TI  - Isoform distinct time-, dose-, and castration-dependent alterations in flavin
      containing monooxygenase expression in mouse liver after 2,3,7,8
      tetrachlorodibenzo-p-dioxin treatment.
AB  - Flavin-containing monooxygenase (FMO) expression in male mouse liver is altered
      after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure or castration. Because
      TCDD is slowly eliminated from the body, we examined hepatic Fmo mRNA alterations
      for up to 32 days following 10 or 64 microg/kg TCDD exposure by oral gavage in
      male C57BL/6J mice. Fmo2 mRNA was significantly induced at 1, 4, and 8 days
      whereas Fmo3 mRNA was also induced at 32 days relative to controls. Fmo3 mRNA
      levels exhibited a dose-dependent increase at 4, 8, and 32 days after exposure;
      Fmo1, Fmo4, and Fmo5 mRNA did not exhibit clear trends. Because castration alone
      also increased Fmo2, Fmo3, and Fmo4 mRNA we examined the combined effects of
      castration and TCDD treatment on FMO expression. A greater than additive effect
      was observed with Fmo2 and Fmo3 mRNA expression. Fmo2 mRNA exhibited a 3-5-fold
      increase after castration or 10 microg/kg TCDD exposure by oral gavage, whereas
      an approximately 20-fold increase was observed between the sham-castrated control
      and castrated TCDD-treated mice. Similarly, treatment with 10 microg/kg TCDD
      alone increased Fmo3 mRNA 130- and 180-fold in the sham-castrated and castrated
      mice compared to their controls respectively, whereas, Fmo3 mRNA increased
      approximately 1900-fold between the sham control and castrated TCDD-treated mice.
      An increase in hepatic Fmo3 protein in TCDD-treated mice was observed by
      immunoblotting and assaying methionine S-oxidase activity. Collectively, these
      results provide evidence for isoform distinct time-, dose-, and castration
      dependent effects of TCDD on FMO expression and suggest cross-talk between TCDD
      and testosterone signal transduction pathways.

PMID- 20036218
TI  - Microglia transplantation attenuates white matter injury in rat chronic ischemia
      model via matrix metalloproteinase-2 inhibition.
AB  - Chronic cerebral ischemia is thought to induce white matter lesions (WMLs), which
      contribute to subcortical vascular dementia. Although glial activation and
      protease upregulation are believed to modify WML pathology, effective therapy
      remains elusive. Here, we compare the efficacy of microglial cell transplantation
      and mesenchymal stem cell (MSC) transplantation in protecting against WML
      development in a chronic cerebral hypoperfusion rat model. A microglial cell line
      (HMO6), MSC cell line (B10) or vehicle (phosphate-buffered saline; PBS) was
      intravenously injected, and the appearance and severity of WMLs were evaluated.
      Transplanted HMO6 and B10 cells migrated to sites of WMLs, including the corpus
      callosum (CC) and caudoputamen (CP), reduced the severity of WMLs, and inhibited
      the accumulation and activation of microglia and astrocytes. Transplantation of
      both cell types reduced the level of matrix metalloproteinase (MMP)-2 mRNA in
      microglia of the CC. MMP-2 protein level and activity were also both greatly
      reduced in the same region. Our results indicate that transplantation of either
      microglial cells or mesenchymal stem cells could inhibit chronic cerebral
      ischemia-induced WML formation by decreasing MMP-2 expression in microglia and
      decreasing MMP-2 activity in the CC region.

PMID- 20036219
TI  - Morphological variability of NADPH diaphorase neurons across areas V1, V2, and V3
      of the common agouti.
AB  - Previous studies have shown a noticeable phenotypic diversity for pyramidal cells
      among cortical areas in the cerebral cortex. Both the extent and systematic
      nature of this variation suggests a correlation with particular aspects of
      cortical processing. Nevertheless, regional variations in the morphology of
      inhibitory cells have not been evaluated with the same detail. In the present
      study we performed a 3D morphometric analysis of 120 NADPH diaphorase (NADPH-d)
      type I neurons in the visual cortex of a South American Hystricomorph rodent, the
      diurnal agouti (Dasyprocta sp.). We found significant differences in morphology
      of NADPH-d type I neurons among visual cortical areas: cells became progressively
      larger and more branched from V1 to V2 and V3. Presumably, the specialized
      morphology of these cells is correlated with different sampling geometry and
      function. The data suggest that area-specific specializations of cortical
      inhibitory circuitry are also present in rodents.

PMID- 20036221
TI  - Cholecystokinin: role in thermoregulation and other aspects of energetics.
AB  - Cholecystokinin (CCK) has long been implicated in body energetics, first as a
      gastrointestinal hormone assisting fat utilization and later as a neuropeptide
      acting either peripherally or centrally in the regulation of body mass. In the
      present review the thermoregulatory role of CCK peptides is reviewed with special
      emphasis on two types of responses, that is hyperthermia (fever) or hypothermia.
      Central microinjection of CCK in rats induces a thermogenic response that can be
      attenuated by CCK2 receptor antagonists, but some authors observed a mild
      hypothermia. By contrast to its central fever-inducing effect, CCK-8 elicits a
      dose-dependent hypothermia on peripheral injection probably acting on CCK1
      receptors in rodents exposed to cold. It is suggested that neuronal CCK may have
      a specific role in the development of hyperthermia and endogenous CCK-ergic
      mechanisms could contribute to the mediation of fever. Recent evidence in rodents
      lacking either of the CCK receptors appears to support the fever-mediating role
      of the peptide. In particular, CCK2 receptors seem to be involved in the
      development of endotoxin fever, while the role of CCK1 receptors could be more
      complex. In line with that idea, rats lacking functional CCK1 receptors show an
      exaggerated fever response, a phenomenon that may be associated with a trait
      different from the absence of this receptor set. The relationship between the
      putative CCK-ergic febrile mechanism and the established central prostaglandin
      mediation is also discussed.

PMID- 20036220
TI  - Visualization and quantification of NAD(H) in brain sections by a novel histo
      enzymatic nitrotetrazolium blue staining technique.
AB  - A histo-enzymatic technique for visualizing and quantifying endogenous NAD(H) in
      brain tissue was developed, based on coupled enzymatic cycling reactions that
      reduce nitrotetrazolium blue chloride to produce formazan. Conditions were used
      where the endogenous level of nicotinamide adenine dinucleotides (NAD(H)) was the
      rate limiting factor for formazan production. Spontaneous degradation of NAD(+)
      that occurs during incubation of thawed tissue was minimized by the addition of
      nicotinamide mononucleotide, an inhibitor of NAD(+) glycohydrolases. Cryostat
      sections of brains obtained from rats immediately after decapitation and 30 min
      later were used to determine the effects of ischemia alone on brain NAD(H) levels
      and neuroanatomic distribution. The ischemic insult resulted in a greater than
      50% decline in the rate of formazan generation in the CA1 pyramidal neuronal
      layer of the hippocampus and in the parietal cortex and striatum, but not in the
      CA3 and dentate gyrus (DG) subregions of the hippocampus. The ischemia-induced
      changes in NAD(H) levels were confirmed by utilizing spectrofluorimetric
      measurements of NAD(H) present in perchloric acid extracts of brain samples. This
      new histo-enzymatic technique is suitable for visualizing and quantifying
      relative NAD(H) levels in the brain. This assay could prove useful in identifying
      region-selective NAD(H) catabolism that may contribute to neurodegeneration.

PMID- 20036222
TI  - Expression of bcl-2 correlates with poor prognosis and modulates migration of
      nasopharyngeal carcinoma cells.
AB  - BACKGROUND: The role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix
      metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC).
      METHODS: From 1996 to 2000, 145 patients with newly diagnosed NPC who were
      treated with high dose radiotherapy were enrolled. The relationship between bcl-2
      expression, TNM stage, and disease-specific survival was analyzed. Furthermore,
      the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and
      cell metastasis. RESULTS: Among the 145 patients, 47 (32.4%) of them were bcl-2
      positive. The expression of bcl-2 was significantly correlated with neck lymph
      node metastasis (p=0.006), and patients with negative bcl-2 expression had better
      disease-free survival (p=0.007). A Cox regression model revealed that only bcl-2
      expression (p=0.023) and stage IV (p=0.043) were statistically significant in the
      prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2
      inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP
      2 in HONE-1 cells. CONCLUSIONS: Bcl-2 expression represents an important and
      easily assayed prognostic factor, and it may play an important role in lymph node
      metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature
      for the prevention of cancer metastasis.

PMID- 20036223
TI  - Increased MMA concentration and body mass index are associated with spontaneous
      abortion in Brazilian women: a pilot study.
AB  - BACKGROUND: The pathophysiology of spontaneous abortion is complex and may
      involve the interaction of genetic and environmental factors. We evaluated the
      predictors of spontaneous abortion in Brazilian pregnant women. The effects of
      age, gestational age, body mass index (BMI), cigarette smoking, alcohol
      ingestion, use of multivitamins and concentrations of vitamins (folate, cobalamin
      and vitamin B6) and vitamin-dependent metabolites were analyzed. METHODS: Study
      population included 100 healthy women that attended pre-natal care in 2 health
      centers of Sao Paulo, Brazil, and in whom pregnancy outcome was known. Folate and
      cobalamin status was measured in blood specimens collected between 4 and 16
      weeks. The genotypes for 8 gene polymorphisms were evaluated by PCR-RFLP.
      RESULTS: Eighty-eight women had normal pregnancy outcome (Group 1), while 12
      experienced a miscarriage after blood collection (Group 2). Increased
      methylmalonic acid (MMA) concentrations were found in Group 2 (median [25th-75th
      percentile]=274 [149-425] nmol/l) relative to Group 1 (138 [98-185]) (P<0.01). No
      differences between the groups were observed for serum cobalamin, serum or red
      cell folate, and serum total homocysteine or allele frequencies for 8
      polymorphisms. In a conditional logistic regression analysis including age,
      gestational age, serum creatinine, MMA, cystathionine, body mass index (BMI),
      cigarette smoking, alcohol ingestion and use of multivitamins the risk of
      abortion was significantly associated with MMA (OR [95% CI]=3.80 [1.36, 10.62]
      per quartile increase in MMA), BMI (OR [95% CI]=5.49 [1.29, 23.39] per quartile)
      and gestational age (OR [95% CI]=0.10 [0.01, 0.77] per increase of interval in
      gestational age). CONCLUSIONS: Increased serum MMA and BMI concentrations are
      associated with spontaneous abortion in Brazilian women.

PMID- 20036224
TI  - Cardiac troponin may be released by ischemia alone, without necrosis.
AB  - Whilst it is formally stated that cardiac troponin is only released when cardiac
      myocytes undergo necrosis, there are a number of clinical situations where
      troponin is present in the circulation, without any apparent cardiac injury. In
      these cases, troponin half-life in the circulation is usually substantially
      shorter than that seen when troponin is released following myocardial infarction
      with frank necrosis. A mechanism has been described in liver, where large
      cytoplasmic molecules can pass from the intra- to extra-cellular space without
      cellular necrosis occurring. This occurs by the formation of membranous blebs
      which bud off from the plasma membrane of the cell. Blebs develop during cellular
      ischemia. If the ischemia is limited and re-oxygenation occurs, the blebs may be
      released into the circulation without rupture of the plasma membrane, resulting
      in a one-off release of cytoplasmic contents including macromolecules. Evidence
      from cardiac studies is presented supporting the presence of membranous blebs in
      cardiac myocytes, enabling troponin to be released from cardiac cells due to
      ischemia alone, without necrosis.

PMID- 20036225
TI  - A meta-analysis of the bradykinin B2 receptor gene --58C/T polymorphism with
      hypertension.
AB  - BACKGROUND AND OBJECTIVE: Numerous studies have attempted to associate -58C/T
      polymorphism of bradykinin B2 receptor gene (BDKRB2) with hypertension, whereas
      results were often irreproducible. We performed a meta-analysis aiming to provide
      a comprehensive evaluation of this polymorphism and hypertension. METHODS: Case
      control reports published in English were searched totaling four studies with six
      populations (823 cases and 916 controls). Random-effects model was applied
      irrespective of between-study heterogeneity, and study quality was assessed in
      duplicate. RESULTS: Compared with -58C allele carriers, those with -58T allele
      had a lower yet nonsignificant risk for hypertension (OR=0.86; 95% CI: 0.68-1.09;
      P=0.21). Lack of significance persisted after combining those with genotypes 
      58TC and -58TT together (OR=0.87; 95% CI: 0.67-1.09; P=0.21) or with -58TC and 
      58CC together (OR=0.75; 95% CI: 0.48-1.18; P=0.22) in association with
      hypertension. Sensitivity analyses by race indicated that comparison of -58T
      versus -58C generated a protective effect for hypertension in Asians (OR=0.77;
      95% CI: 0.58-1.02; P=0.07) and African-Americans (OR=0.65; 95% CI: 0.43-0.98;
      P=0.04), but a risk effect in Caucasians (OR=1.22; 95% CI: 0.92-1.61; P=0.17). No
      publication bias was observed. CONCLUSIONS: Our results suggested that -58T
      allele exhibited a protective effect on hypertension in Asians and African
      Americans, yet a risk effect in Caucasians.

PMID- 20036226
TI  - Empirical models for dosage optimization of four beta-lactams in critically ill
      septic patients based on therapeutic drug monitoring of amikacin.
AB  - OBJECTIVES: The study aims to develop empirical models able to predict the
      pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic
      drug monitoring (TDM), in order to optimize their dosage regimens. DESIGN AND
      METHODS: 69 critically ill septic patients were included. All received a first
      dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or
      meropenem. A multivariate analysis was performed to predict the beta-lactam PK
      using AMK PK parameters estimated from TDM and using pathophysiological
      variables. RESULTS: An optimal prediction model was identified for each PK
      parameter of each beta-lactam. The best predictor of each model was one of the
      AMK PK parameters estimated from TDM. Other variables included colloid solution,
      renal and hepatic biomarkers, age and body weight. CONCLUSION: PK of the four
      beta-lactams could be easily and rapidly predicted in critically ill septic
      patients using the AMK TDM. These predictions could improve the beta-lactam
      dosages in clinical practice.

PMID- 20036227
TI  - Highly conserved functions of the Brachyury gene on morphogenetic movements:
      insight from the early-diverging phylum Ctenophora.
AB  - Brachyury, a member of the T-box transcription family identified in a diverse
      array of metazoans, was initially recognized for its function in mesoderm
      formation and notochord differentiation in vertebrates; however, its ancestral
      role has been suggested to be in control of morphogenetic movements. Here, we
      show that morpholino oligonucleotide knockdown of Brachyury (MlBra) in embryos of
      a ctenophore, one of the most ancient groups of animals, prevents the
      invagination of MlBra expressing stomodeal cells and is rescued with
      corresponding RNA injections. Injection of RNA encoding a dominant-interfering
      construct of MlBra causes identical phenotypes to that of RNA encoding a dominant
      interfering form of Xenopus Brachyury (Xbra) in Xenopus embryos. Both injected
      embryos down-regulate Xbra downstream genes, Xbra itself and Xwnt11 but not axial
      mesodermal markers, resulting in failure to complete gastrulation due to loss of
      convergent extension movements. Moreover, animal cap assay reveals that MlBra
      induces Xwnt11 like Xbra. Overall results using Xenopus embryos show that these
      two genes are functionally interchangeable. These functional experiments
      demonstrate for the first time in a basal metazoan that the primitive role of
      Brachyury is to regulate morphogenetic movements, rather than to specify
      endomesodermal fates, and the role is conserved between non-bilaterian metazoans
      and vertebrates.

PMID- 20036228
TI  - hth maintains the pool of eye progenitors and its downregulation by Dpp and Hh
      couples retinal fate acquisition with cell cycle exit.
AB  - During Drosophila eye development, recruitment of retinal precursors from a pool
      of progenitor cells is tightly coupled to proliferation control. However, how
      this coupling operates is still unclear. Here we show that the transcription
      factor hth, together with eyeless, is required to stimulate proliferation of
      progenitor cells. Accordingly, knocking down hth expression results in severely
      reduced eyes. Our experiments reveal three additional functions for hth: the cell
      cycle of progenitors is characterized by a relatively long G2 phase, which makes
      them prone to enter mitosis; hth represses the burst of string/cdc25 expression
      that precedes G1 arrest, and also the early expression of the proneural gene
      atonal. Thereby, hth maintains the proliferative and undifferentiated state of
      eye progenitors. Furthermore, we show that the G1 synchronization that
      characterizes retinal precursors is the result of the spatially controlled
      repression of hth by Dpp and Hh, and not of an actively induced cell cycle
      arrest. We integrate these results in a model of the early steps of eye
      development that links proliferation control and differential gene expression
      with patterning signals.

PMID- 20036229
TI  - Deficiency of smarcal1 causes cell cycle arrest and developmental abnormalities
      in zebrafish.
AB  - Mutations in SMARCAL1 cause Schimke Immuno-Osseous Dysplasia (SIOD), an autosomal
      recessive multisystem developmental disease characterized by growth retardation,
      T-cell deficiency, bone marrow failure, anemia and renal failure. SMARCAL1
      encodes an ATP-driven annealing helicase. However, the biological function of
      SMARCAL1 and the molecular basis of SIOD remain largely unclear. In this work, we
      cloned the zebrafish homologue of the human SMARCAL1 gene and found that smarcal1
      regulated cell cycle progression. Morpholino knockdown of smarcal1 in zebrafish
      recapitulated developmental abnormalities in SIOD patients, including growth
      retardation, craniofacial abnormality, and haematopoietic and vascular defects.
      Lack of smarcal1 caused G0/G1 cell cycle arrest and induced cell apoptosis.
      Furthermore, using Electrophoretic Mobility Shift Assay and reporter assay, we
      found that SMARCAL1 was transcriptionally inhibited by E2F6, an important cell
      cycle regulator. Over-expression of E2F6 in zebrafish embryos reduced the
      expression of smarcal1 mRNA and induced developmental defects similar to those in
      smarcal1 morphants. These results suggest that SIOD may be caused by defects in
      cell cycle regulation. Our study provides a model of SIOD and reveals its
      cellular and molecular bases.

PMID- 20036230
TI  - The Drosophila LEM-domain protein MAN1 antagonizes BMP signaling at the
      neuromuscular junction and the wing crossveins.
AB  - BMP signaling responses are refined by distinct secreted and intracellular
      antagonists in different cellular and temporal contexts. Here, we show that the
      nuclear LEM-domain protein MAN1 is a tissue-specific antagonist of BMP signaling
      in Drosophila. MAN1 contains two potential Mad-binding sites. We generated
      MAN1DeltaC mutants, harbouring a MAN1 protein that lacks part of the C-terminus
      including the RNA recognition motif, a putative Mad-binding domain. MAN1DeltaC
      mutants show wing crossvein (CV) patterning defects but no detectable alterations
      in nuclear morphology. MAN1(DeltaC) pupal wings display expanded phospho-Mad
      (pMad) accumulation and ectopic expression of the BMP-responsive gene
      crossveinless-2 (cv-2) indicating that MAN1 restricts BMP signaling. Conversely,
      MAN1 overexpression in wing imaginal discs inhibited crossvein development and
      BMP signaling responses. MAN1 is expressed at high levels in pupal wing veins and
      can be activated in intervein regions by ectopic BMP signaling. The specific
      upregulation of MAN1 in pupal wing veins may thus represent a negative feedback
      circuit that limits BMP signaling during CV formation. MAN1DeltaC flies also show
      reduced locomotor activity, and electrophysiology recordings in MAN1DeltaC larvae
      uncover a new presynaptic role of MAN1 at the neuromuscular junction (NMJ).
      Genetic interaction experiments suggest that MAN1 is a BMP signaling antagonist
      both at the NMJ and during CV formation.

PMID- 20036231
TI  - Baicalin suppresses lung carcinoma and lung metastasis by SOD mimic and HIF
      1alpha inhibition.
AB  - The dose-related toxicity of anticancer drugs in chemotherapy of clinical
      carcinoma is the major obstacle to prolonged survival, we want to investigate
      selective therapeutic efficacy of baicalin on lung carcinoma and explain the
      basis underlying this phenomenon. In vitro, baicalin inhibited cell proliferation
      of human lung carcinoma A549 and mouse lewis lung cancer (LLC) in a dose- and
      time-dependent manner. The inhibitory activity of baicalin against cancer cells
      was promoted by superoxide dismutase (SOD) addition or hypoxia-inducible factor
      1alpha (HIF-1alpha) knockdown and was reduced by SOD knockdown but not hypoxia.
      In vivo, baicalin suppressed tumor growth and prolonged survival in C57BL/6 mice
      bearing LLC tumor and nude mice bearing A549 carcinoma without systemic toxicity.
      Further studies showed that baicalin inhibited HIF-1alpha and enhanced SOD
      activity without affecting catalase and glutathione-S-transferase (GST) in cancer
      cells. In addition, baicalin also exhibited a superoxide anion scavenging
      activity. In conclusion, baicalin could selectively suppress lung carcinoma and
      lung metastasis by SOD mimic and HIF-1alpha inhibition.

PMID- 20036232
TI  - Cell guidance by magnetic nanowires.
AB  - The phenomenon of contact guidance on thin fibers has been known since the
      beginning of the 20th century when Harrison studied cells growing on fibers from
      spider's web. Since then many studies have been performed on structured surfaces
      and fibers. Here we present a new way to induce guidance of cells or cell
      processes using magnetic nanowires. We have manufactured magnetic Ni-nanowires
      (200 nm in diameter and 40 microm long) with a template-based electro-deposition
      method. Drops of a nanowire/ethanol suspension were placed on glass cover slips.
      The nanowires were aligned in an external magnetic field and adhered to the cover
      slips after evaporation of the ethanol. When the wires had adhered, the magnetic
      field was removed. L929 fibroblasts and dissociated dorsal root ganglia (DRG)
      neurons from mice were cultured on the nanowire-coated cover slips for 24 h and
      72 h respectively. The fibroblasts were affected by the aligned nanowires and
      displayed contact guidance. Regenerated axons also displayed contact guidance on
      the wires. There were no overt signs of toxicity caused by Ni-wires. Aligned
      magnetic nanowires can be useful for lab-on-a-chip devices and medical nerve
      grafts.

PMID- 20036234
TI  - Involvement of 1,25D3-MARRS (membrane associated, rapid response steroid
      binding), a novel vitamin D receptor, in growth inhibition of breast cancer
      cells.
AB  - In addition to classical roles in calcium homeostasis and bone development, 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3] inhibits the growth of several cancer types,
      including breast cancer. Although cellular effects of 1,25(OH)2D3 traditionally
      have been attributed to activation of a nuclear vitamin D receptor (VDR), a novel
      receptor for 1,25(OH)2D3 called 1,25D3-MARRS (membrane-associated, rapid response
      steroid-binding) protein was identified recently. The purpose of this study was
      to determine if the level of 1,25D3-MARRS expression modulates 1,25(OH)2D3
      activity in breast cancer cells. Relative levels of 1,25D3-MARRS protein in MCF
      7, MDA MB 231, and MCF-10A cells were estimated by real-time RT-PCR and Western
      blotting. To determine if 1,25D3-MARRS receptor was involved in the growth
      inhibitory effects of 1,25(OH)2D3 in MCF-7 cells, a ribozyme construct designed
      to knock down 1,25D(3)-MARRS mRNA was stably transfected into MCF-7 cells. MCF-7
      clones in which 1,25D3-MARRS receptor expression was reduced showed increased
      sensitivity to 1,25(OH)2D3 ( IC(50) 56+/-24 nM) compared to controls (319+/-181
      nM; P<0.05). Reduction in 1,25D3-MARRS receptor lengthened the doubling time in
      transfectants treated with 1,25(OH)2D3. Knockdown of 1,25D3-MARRS receptor also
      increased the sensitivity of MCF-7 cells to the vitamin D analogs KH1060 and
      MC903, but not to unrelated agents (all-trans retinoic acid, paclitaxel,
      serum/glucose starvation, or the isoflavone, pomiferin). These results suggest
      that 1,25D3-MARRS receptor expression interferes with the growth inhibitory
      activity of 1,25(OH)2D3 in breast cancer cells, possibly through the nuclear VDR.
      Further research should examine the potential for pharmacological or natural
      agents that modify 1,25D3-MARRS expression or activity as anticancer agents.

PMID- 20036233
TI  - Sdc1 negatively modulates carcinoma cell motility and invasion.
AB  - During cancer progression, tumor cells eventually invade the surrounding collagen
      rich extracellular matrix. Here we show that squamous cell carcinoma cells
      strongly adhere to Type I collagen substrates but display limited motility and
      invasion on collagen barriers. Further analysis revealed that in addition to the
      alpha2beta1 integrin, a second collagen receptor was identified as Syndecan-1
      (Sdc1), a cell surface heparan sulfate proteoglycan. We demonstrate that siRNA
      mediated depletion of Sdc1 reduced adhesion efficiency to collagen I, whereas
      knockdown of Sdc4 was without effect. Importantly, silencing Sdc1 expression
      caused reduced focal adhesion plaque formation and enhanced cell spreading and
      motility on collagen I substrates, but did not alter cell motility on other ECM
      substrates. Sdc1 depletion ablated adhesion-induced RhoA activation. In contrast,
      Rac1 was strongly activated following Sdc1 knockdown, suggesting that Sdc1 may
      mediate the link between integrin-induced actin remodeling and motility. Taken
      together, these data substantiate the existence of a co-adhesion receptor system
      in tumor cells, whereby Sdc1 functions as a key regulator of cell motility and
      cell invasion by modulating RhoA and Rac activity. Downregulation of Sdc1
      expression during carcinoma progression may represent a mechanism by which tumor
      cells become more invasive and metastatic.

PMID- 20036235
TI  - Non-CDK-bound p27 (p27(NCDK)) is a marker for cell stress and is regulated
      through the Akt/PKB and AMPK-kinase pathways.
AB  - p27Kip1 (p27) tumour suppressor protein is regulated by multiple mechanisms
      including its turnover, localization and complex formation with its key targets,
      cyclin-dependent kinases (CDK) and cyclins. We have earlier shown that p27 exists
      in cells in a form that lacks cyclin/CDK interactions (hence non-CDK, p27(NCDK))
      but the nature of p27(NCDK) has remained unresolved. Here we demonstrate that the
      epitope recognized by the p27(NCDK)-specific antibody resides in the p27 CDK
      interaction domain and that p27(NCDK) is regulated by the balance of CDK
      inhibitors and cyclin-CDK complexes. We find that signalling by cellular growth
      promoting pathways, like phosphoinositol 3-kinase (PI3K) and specifically Akt/PKB
      kinase, inversely correlates with p27(NCDK) levels whereas total p27 levels are
      unaffected. p27(NCDK), but not total p27, is increased by cellular perturbations
      such as hyperosmotic and metabolic stress and activation of AMP-activated protein
      kinase (AMPK). By using AMPK catalytic subunit proficient and deficient cells we
      further demonstrate that the AMPK pathway governs p27(NCDK) responses to
      metabolic stress and PI3K inhibition. These results indicate that p27(NCDK) is a
      sensitive marker for both cell stress and proliferation over and above p27 and is
      regulated by Akt/PKB and AMPK pathways.

PMID- 20036236
TI  - Localisation of opticin in human proliferative retinal disease.
AB  - This study sought to determine the distribution of opticin, an extracellular
      matrix small leucine-rich repeat protein secreted by the non-pigmented ciliary
      body epithelium (CBE), in pathological eye tissues including posterior hyaloid
      membranes (PHM) and epiretinal membranes (ERM) from subjects with proliferative
      diabetic retinopathy (PDR), central retinal vein occlusion (CRVO) and
      proliferative vitreoretinopathy (PVR). Eight enucleated eyes and eleven
      surgically excised PHMs/ERMs from patients with PDR, CRVO or PVR were analysed by
      immunohistochemistry for the presence and distribution of opticin, vitreous
      (delineated by a type II collagen antibody) and blood vessels (using CD31 and
      CD34 antibodies as endothelial markers). Opticin was present at the basal surface
      of the non-pigmented CBE and, in a patchy distribution, within CBE cells in all 8
      enucleated globes. It also co-localised with the type II collagen of vitreous,
      where present, in these eyes. Opticin was present in 16 of the 19 PHMs/ERMs,
      where it was arranged in layers (10 membranes), diffusely (4 membranes) or in
      foci (2 membranes). Where in a layered pattern, opticin co-localised with
      vitreous type II collagen incorporated into the membrane, whereas the other two
      patterns did not co-localise with type II collagen labelling. We concluded that
      even in advanced proliferative retinal disease, the CBE continues to express and
      secrete opticin. Opticin was co-distributed with vitreous type II collagen and
      was also present in the pre-retinal membranes of proliferative retinopathies,
      where it could play a role in their development.

PMID- 20036237
TI  - Dyskeratosis congenita and limbal stem cell deficiency.
AB  - In light of the latest developments in the field of molecular hematology, we
      herein discuss the reported cases that have presented dyskeratosis congenita as
      one of the inherited stem cell diseases causing limbal stem cell deficiency.

PMID- 20036238
TI  - Head-up tilt lowers IOP and improves RGC dysfunction in glaucomatous DBA/2J mice.
AB  - The inbred DBA/2J (D2) mouse strain is a well established model of spontaneously
      elevated intraocular pressure (IOP), progressive glaucomatous loss of retinal
      ganglion cells (RGCs), and early damage of RGC axons at the level of optic nerve
      head. Pattern electroretinogram (PERG) studies have shown that surviving RGCs in
      mice 6-12-month-old may be dysfunctional. RGC dysfunction seems to be IOP
      dependent, since it may be exacerbated by means of acute IOP elevation with head
      down body tilt. Here we test the hypothesis that head-up body posture lowers IOP,
      resulting in improvement of PERG amplitude in aged D2 mice with glaucoma. We show
      that head-up body tilt induces age-independent IOP lowering whose magnitude
      increases with the angle of tilt. For a fixed angle (-60 degrees ) of head-up
      tilt, IOP progressively decreases with a time constant of about 5 min and
      stabilizes at a value lower by about 5-6 mm Hg compared to the baseline. Head-up
      tilt also results in an improvement of PERG amplitude in older D2 mice with
      glaucoma but not in younger D2 mice without glaucoma. Improvement of PERG
      amplitude in aged D2 mice upon head-up-induced IOP lowering is consistent with
      the idea that RGCs undergo a stage of IOP-dependent, reversible dysfunction
      before death. The head-up IOP/PERG protocol may represent a non-invasive way to
      probe the potential for recovery of RGC dysfunction in D2 mice.

PMID- 20036239
TI  - Effect of pro-inflammatory mediators on membrane-associated mucins expressed by
      human ocular surface epithelial cells.
AB  - Membrane-associated mucins are altered on the ocular surface in non-Sjogren's dry
      eye. This study sought to determine if inflammatory mediators, present in tears
      of dry eye patients, regulate membrane-associated mucins MUC1 and -16 at the
      level of gene expression, protein biosynthesis and/or ectodomain release. A human
      corneal limbal epithelial cell line (HCLE), which produces membrane-associated
      mucins, was used. Cells were treated with interleukin (IL)-6, -8, or -17, tumor
      necrosis factor-alpha (TNF-alpha), and Interferon-gamma (IFN-gamma), or a
      combination of TNF-alpha and IFN-gamma, or IFN-gamma and IL-17, for 1, 6, 24, or
      48 h. Presence of receptors for these mediators was verified by RT-PCR. Effects
      of the cytokines on expression levels of MUC1 and -16 were determined by real
      time PCR, and on mucin protein biosynthesis and ectodomain release in cell
      lysates and culture media, respectively, by immunoblot analysis. TNF-alpha and
      IFN-gamma each significantly induced MUC1 expression, cellular protein content
      and ectodomain release over time. Combined treatment with the two cytokines was
      not additive. By comparison, one of the inflammatory mediators, IFN-gamma,
      affected all three parameters-gene expression, cellular protein, and ectodomain
      release-for MUC16. Combined treatment with TNF-alpha and IFN-gamma showed effects
      similar to IFN-gamma alone, except that ectodomain release followed that of TNF
      alpha, which induced MUC16 ectodomain release. In conclusion, inflammatory
      mediators present in tears of dry eye patients can affect MUC1 and -16 on corneal
      epithelial cells and may be responsible for alterations of surface mucins in dry
      eye.

PMID- 20036241
TI  - Characterization of iodothyronine sulfotransferase activity in the cytosol of
      Rana catesbeiana tadpole tissues.
AB  - We have investigated the sulfation of thyroid hormones (THs) in the cytosol from
      Rana catesbeiana tadpole tissues. Sulfation of 3,3',5-triiodothyronine (T(3)) by
      the liver cytosol, which was dependent on protein amount, incubation time, and
      temperature, suggested the presence of TH sulfotransferases (SULTs) in the liver.
      The apparent Michaelis-Menten constant (K(m)) of the liver cytosol was 0.22
      microM for T(3), and the apparent maximum velocity (V(max)) of the liver cytosol
      was 7.65 pmol/min/mg protein for T(3). Iodothyronine sulfating activity in the
      liver cytosol was increased in tadpoles at premetamorphic (stages IX-X) and
      metamorphic climax (stage XX) stages, and in adult frogs. The substrate
      preference of iodothyronine sulfation for the liver cytosol from tadpoles (stage
      X) was: 3,3',5'-triiodothyronine>T(3)>3,3',5,5'-tetraiodothyroacetic acid>3,3',5
      triiodothyroacetic acid, T(4), 3-iodothyronine>3,5-diiodothyronine. Several
      halogenated phenols were potent inhibitors (IC(50)=0.15-0.21 microM). The
      substrate preference for T(3) was gradually lost by the onset of metamorphic
      climax stages. These enzymatic characteristics of iodothyronine sulfation in the
      liver cytosol from tadpoles resembled those of mammalian phenol SULTs, except
      that the tadpole cytosol had a higher affinity (one or two orders of magnitude)
      for T(3) than mammalian SULTs. These results suggested that an enzyme homologous
      to mammalian phenol SULT (SULT1) may be involved in TH metabolism in tadpoles.

PMID- 20036242
TI  - Neither testosterone levels nor aggression decrease when the male Mongolian
      gerbil (Meriones unguiculatus) displays paternal behavior.
AB  - The first studies that correlated mammalian paternal behavior and testosterone
      levels indicated that the concentration of this steroid hormone decreases when
      males exhibit paternal care. However, recent studies have also shown that
      testosterone levels do not decrease when males display paternal behavior. In this
      study, we measured testosterone levels in plasma throughout the reproductive
      cycle of the Mongolian gerbil. Testosterone concentrations were correlated with
      paternal care as well as aggression. We also examined whether there is a trade
      off between paternal behavior and aggression in this mammal. Our results show
      that Mongolian gerbil testosterone levels do not decrease when the males give
      paternal care. Likewise, male Mongolian gerbils exhibit high levels of aggression
      while displaying paternal behavior, indicating that there is no trade-off between
      aggression and paternal behavior. More studies are needed to determine whether
      testosterone is involved in the regulation of paternal behavior in this rodent.

PMID- 20036240
TI  - The effects of sympathetic outflow on upregulation of vanilloid receptors TRPV(1)
      in primary afferent neurons evoked by intradermal capsaicin.
AB  - The vanilloid receptor TRPV(1) is a key nociceptive molecule located in primary
      afferent nociceptive neurons in dorsal root ganglia (DRG) for initiating
      neurogenic inflammation and pain. Our recent study demonstrates that up
      regulation of TRPV(1) receptors by intradermal injection of capsaicin is
      modulated by activation of the protein kinase C (PKC) cascade. Neurogenic
      inflammation and pain resulting from capsaicin injection are sympathetically
      dependent, responding to norepinephrine, adenosine 5'-triphosphate (ATP) and/or
      neuropeptide Y released from sympathetic efferents. In a rat model of acute
      neurogenic inflammatory pain produced by capsaicin injection, we used
      immunofluorescence and Western blots combined with pharmacology and surgical
      sympathectomies to analyze whether the capsaicin-evoked up-regulation of TRPV(1)
      in DRG neurons is affected by sympathetic outflow by way of activating the PKC
      cascade. Sympathetic denervation reduced significantly the capsaicin-evoked
      expressions of TRPV(1), calcitonin gene-related peptide and/or phosphorylated PKC
      and their co-expression. These reductions could be restored by exogenous
      pretreatment with an analog of ATP, alpha,beta-methylene ATP. Inhibition of PKC
      with chelerythrine chloride prevented the ATP effect. Consistent results were
      obtained from experiments in which capsaicin-evoked changes in cutaneous
      inflammation (vasodilation and edema) were examined after sympathetic
      denervation, and the effects of the above pharmacological manipulations were
      evaluated. Our findings suggest that the capsaicin-evoked up-regulation of
      TRPV(1) receptors in DRG neurons is modulated sympathetically by the action of
      ATP released from sympathetic efferents to activate the PKC cascade. Thus, this
      study proposes a potential new mechanism of sympathetic modulation of neurogenic
      inflammation.

PMID- 20036243
TI  - Combining positional scanning peptide libraries, HLA-DR transfectants and
      bioinformatics to dissect the epitope spectrum of HLA class II cross-restricted
      CD4+ T cell clones.
AB  - The use of positional scanning peptide libraries in combination with biometrical
      analysis is one of the few approaches, which allows the identification of
      stimulatory peptides for T cells of unknown specificity. Despite the successful
      application of this strategy in different studies, not every T cell is suited for
      analysis. For as yet unknown reasons some T cells do not recognize these highly
      complex libraries, and even more importantly the predictive capacity of the
      current approach shows high variability among individual T cell clones and their
      TCRs. A number of factors probably contribute to differences in T cell
      recognition and have to be taken into account in order to overcome these
      difficulties. Our results suggest that the ability of some T cells to recognize
      peptides in the context of more than one HLA class II molecule expressed by
      autologous APCs could diminish the predictive capacity of the approach. In
      contrast, the use of B cell lines expressing single HLA class II molecules as
      APCs instead of autologous peripheral blood mononuclear cells markedly improves
      the capacity to identify target peptides for this type of T cells.

PMID- 20036244
TI  - Role of xylem consumption on osmoregulation in Macrosiphum euphorbiae (Thomas).
AB  - Aphids are phloem feeders that occasionally ingest xylem sap. The duration of
      xylem consumption by Macrosiphum euphorbiae (Hemiptera: Aphididae) was positively
      correlated with the level of dehydration of alate aphids of different ages after
      a period of starvation, supporting the hypothesis that aphids ingest xylem sap to
      replenish their water balance. However, the duration of xylem sap ingestion but
      not phloem sap consumption varied in unstarved alate adults of different ages.
      Furthermore, both alate and apterous aphids ingested xylem sap at the end of
      their life, when aphids were not dehydrated but when fecundity started to
      decrease. Fecundity was negatively correlated with the proportion of time spent
      ingesting xylem sap, and that over the entire reproductive life of alate and
      apterous aphids. The lower proportion of xylem ingested by apterous than by alate
      aphids during the first few days of adult life may be related to a higher
      symbiont density in apterous morphs. As previous studies have demonstrated a
      relationship between sucrose assimilation, which is directly influenced by
      fecundity and symbiont density, and osmoregulation, we suggest that xylem
      consumption may play a role in the osmoregulation of haemolymph of aphids.

PMID- 20036245
TI  - Funny current provides a relatively modest contribution to spontaneous beating
      rate regulation of human and rabbit sinoatrial node cells.

PMID- 20036246
TI  - Modulation of canine cardiac sodium current by Apelin.
AB  - Apelin, a ligand of the G protein-coupled putative angiotensin II-like receptor
      (APJ-R), exerts strong vasodilating, cardiac inotropic and chronotropic actions.
      Its expression is highly up-regulated during heart failure. Apelin also increases
      cardiac conduction speed and excitability. While our knowledge of apelin
      cardiovascular actions is growing, our understanding of the physiological
      mechanisms behind the cardiac effects remains limited. We tested the effects of
      apelin on the cardiac sodium current (I(Na)) using patch clamp technique on
      cardiac myocytes acutely dissociated from dog ventricle. We found that apelin-13
      and apelin-17 increased peak I(Na) by 39% and 61% and shifted its mid-activation
      potential by -6.8+/-0.6 mV and -17+/-1 mV respectively thus increasing channel
      opening at negative voltage. Apelin also slowed I(Na) recovery from inactivation.
      The effects of apelin on I(Na) amplitude were linked to activation of protein
      kinase C. Apelin also increased I(Na) "window" current by up to 600% suggesting
      that changes in intracellular sodium may contribute to the apelin inotropic
      effects. Our results reveal for the first time the effects of apelin on I(Na).
      These effects are likely to modulate cardiac conduction and excitability and may
      have beneficial antiarrhythmic action in sodium chanelopathies such as Brugada
      Syndrome where I(Na) amplitude is reduced.

PMID- 20036247
TI  - Role of growth factor receptor transactivation in high glucose-induced increased
      levels of Gq/11alpha and signaling in vascular smooth muscle cells.
AB  - We have recently shown that high glucose increased the expression of Gq/11alpha,
      PLCbeta and mediated signaling in A10 vascular smooth muscle cells (VSMC). Since
      high glucose has been shown to increase growth factor receptor activation, we
      investigated the role of epidermal growth factor receptor (EGF-R) and platelet
      derived growth factor receptor (PDGF-R) transactivation in high glucose-induced
      enhanced expression of Gq/11alpha and PLCbeta. Pre-treatment of A10 VSMC with
      high glucose (26 mM) for 3 days, increased the levels of Gqalpha, G11alpha,
      PLCbeta-1 and PLCbeta-2 proteins which were restored to control levels by AG1478,
      an inhibitor of EGF-R, AG1295, an inhibitor of PDGF-R and PP2, an inhibitor of c
      Src but not by PP3. In addition, endothelin-1 (ET-1)-stimulated production of
      IP(3) that was enhanced by high glucose was also restored towards control levels
      by AG1478, AG1295 and PP2. High glucose also increased the phosphorylation of EGF
      R and PDGF-R which was abolished by AG1478, AG1295 and PP2. Furthermore, high
      glucose-induced enhanced levels of Gqalpha, G11alpha and PLCbeta were also
      attenuated by PD98059, an inhibitor of mitogen-activated protein kinase (MAPK)
      and wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3-K). In
      addition, AG1478 and AG1295, also attenuated high glucose-induced enhanced
      phosphorylation of ERK1/2 and AKT. Furthermore, high glucose augmented the
      phosphorylation of c-Src which was attenuated by antioxidant, DPI. These results
      suggest that oxidative stress through the activation of c-Src and resultant
      transactivation of growth factor receptor contributes to the high glucose-induced
      enhanced expression of Gq/11alpha/PLC and -mediated cell signaling through
      MAPK/PI3K pathway.

PMID- 20036249
TI  - Crystal structure of a thermophilic GrpE protein: insight into thermosensing
      function for the DnaK chaperone system.
AB  - A homodimeric GrpE protein functions as a nucleotide exchange factor of the
      eubacterium DnaK molecular chaperone system. The co-chaperone GrpE accelerates
      ADP dissociation from, and promotes ATP binding to, DnaK, which cooperatively
      facilitates the DnaK chaperone cycle with another co-chaperone, DnaJ. GrpE
      characteristically undergoes two-step conformational changes in response to
      elevation of the environmental temperature. In the first transition at heat-shock
      temperatures, a fully reversible and functionally deficient structural alteration
      takes place in GrpE, and then the higher temperatures lead to the irreversible
      dissociation of the GrpE dimer into monomers as the second transition. GrpE is
      also thought to be a thermosensor of the DnaK system, since it is the only member
      of the DnaK system that changes its structure reversibly and loses its function
      at heat-shock temperatures of various organisms. We here report the crystal
      structure of GrpE from Thermus thermophilus HB8 (GrpE(Tth)) at 3.23 A resolution.
      The resolved structure is compared with that of GrpE from mesophilic Escherichia
      coli (GrpE(Eco)), revealing structural similarities, particularly in the DnaK
      interaction regions, and structural characteristics for the thermal stability of
      GrpE(Tth). In addition, the structure analysis raised the possibility that the
      polypeptide chain in the reported GrpE(Eco) structure was misinterpreted.
      Comparison of these two GrpE structures combined with the results of limited
      proteolysis experiments provides insight into the protein dynamics of GrpE(Tth)
      correlated with the shift of temperature, and also suggests that the localized
      and partial unfolding at the plausible DnaK interaction sites of GrpE(Tth) causes
      functional deficiency of nucleotide exchange factor in response to the heat
      shock.

PMID- 20036248
TI  - Evolutionary trace annotation of protein function in the structural proteome.
AB  - By design, structural genomics (SG) solves many structures that cannot be
      assigned function based on homology to known proteins. Alternative function
      annotation methods are therefore needed and this study focuses on function
      prediction with three-dimensional (3D) templates: small structural motifs built
      of just a few functionally critical residues. Although experimentally proven
      functional residues are scarce, we show here that Evolutionary Trace (ET)
      rankings of residue importance are sufficient to build 3D templates, match them,
      and then assign Gene Ontology (GO) functions in enzymes and non-enzymes alike. In
      a high-specificity mode, this Evolutionary Trace Annotation (ETA) method covered
      half (53%) of the 2384 annotated SG protein controls. Three-quarters (76%) of
      predictions were both correct and complete. The positive predictive value for all
      GO depths (all-depth PPV) was 84%, and it rose to 94% over GO depths 1-3 (depth 3
      PPV). In a high-sensitivity mode, coverage rose significantly (84%), while
      accuracy fell moderately: 68% of predictions were both correct and complete, all
      depth PPV was 75%, and depth 3 PPV was 86%. These data concur with prior
      mutational experiments showing that ET rank information identifies key functional
      determinants in proteins. In practice, ETA predicted functions in 42% of 3461
      unannotated SG proteins. In 529 cases--including 280 non-enzymes and 21 for metal
      ion ligands--the expected accuracy is 84% at any GO depth and 94% down to GO
      depth 3, while for the remaining 931 the expected accuracies are 60% and 71%,
      respectively. Thus, local structural comparisons of evolutionarily important
      residues can help decipher protein functions to known reliability levels and
      without prior assumption on functional mechanisms. ETA is available at
      http://mammoth.bcm.tmc.edu/eta.

PMID- 20036250
TI  - Combining EPR with fluorescence spectroscopy to monitor conformational changes at
      the myosin nucleotide pocket.
AB  - We used spin-labeled nucleotide analogs and fluorescence spectroscopy to monitor
      conformational changes at the nucleotide-binding site of wild-type Dictyostelium
      discoideum (WT) myosin and a construct containing a single tryptophan at position
      F239 near the switch 1 loop. Electron paramagnetic resonance (EPR) spectroscopy
      and tryptophan fluorescence have been used previously to investigate changes at
      the myosin nucleotide site. A limitation of fluorescence spectroscopy is that it
      must be done on mutated myosins containing only a single tryptophan. A limitation
      of EPR spectroscopy is that one infers protein conformational changes from
      alterations in the mobility of an attached probe. These limitations have led to
      controversies regarding conclusions reached by the two approaches. For the first
      time, the data presented here allow direct correlations to be made between the
      results from the two spectroscopic approaches on the same proteins and extend our
      previous EPR studies to a nonmuscle myosin. EPR probe mobility indicates that the
      conformation of the nucleotide pocket of the WTSLADP (spin-labeled ADP) complex
      is similar to that of skeletal myosin. The pocket is closed in the absence of
      actin for both diphosphate and triphosphate nucleotide states. In the actin
      myosin diphosphate state, the pocket is in equilibrium between closed and open
      conformations, with the open conformation slightly more favorable than that seen
      for fast skeletal actomyosin. The EPR spectra for the mutant show similar
      conformations to skeletal myosin, with one exception: in the absence of actin,
      the nucleotide pocket of the mutant displays an open component that was
      approximately 4-5 kJ/mol more favorable than in skeletal or WT myosin. These
      observations resolve the controversies between the two techniques. The data from
      both techniques confirm that binding of myosin to actin alters the conformation
      of the myosin nucleotide pocket with similar but not identical energetics in both
      muscle and nonmuscle myosins.

PMID- 20036251
TI  - N-myristoyltransferase from Leishmania donovani: structural and functional
      characterisation of a potential drug target for visceral leishmaniasis.
AB  - N-Myristoyltransferase (NMT) catalyses the attachment of the 14-carbon saturated
      fatty acid, myristate, to the amino-terminal glycine residue of a subset of
      eukaryotic proteins that function in multiple cellular processes, including
      vesicular protein trafficking and signal transduction. In these pathways, N
      myristoylation facilitates association of substrate proteins with membranes or
      the hydrophobic domains of other partner peptides. NMT function is essential for
      viability in all cell types tested to date, demonstrating that this enzyme has
      potential as a target for drug development. Here, we provide genetic evidence
      that NMT is likely to be essential for viability in insect stages of the
      pathogenic protozoan parasite, Leishmania donovani, causative agent of the
      tropical infectious disease, visceral leishmaniasis. The open reading frame of L.
      donovani NMT has been amplified and used to overproduce active recombinant enzyme
      in Escherichia coli, as demonstrated by gel mobility shift assays of ligand
      binding and peptide-myristoylation activity in scintillation proximity assays.
      The purified protein has been crystallized in complex with the non-hydrolysable
      substrate analogue S-(2-oxo)pentadecyl-CoA, and its structure was solved by
      molecular replacement at 1.4 A resolution. The structure has as its defining
      feature a 14-stranded twisted beta-sheet on which helices are packed so as to
      form an extended and curved substrate-binding groove running across two protein
      lobes. The fatty acyl-CoA is largely buried in the N-terminal lobe, its binding
      leading to the loosening of a flap, which in unliganded NMT structures, occludes
      the protein substrate binding site in the carboxy-terminal lobe. These studies
      validate L. donovani NMT as a potential target for development of new therapeutic
      agents against visceral leishmaniasis.

PMID- 20036252
TI  - Specific structural features of the N-acetylmuramoyl-L-alanine amidase AmiD from
      Escherichia coli and mechanistic implications for enzymes of this family.
AB  - AmiD is the fifth identified N-acetylmuramoyl-L-alanine zinc amidase of
      Escherichia coli. This periplasmic lipoprotein is anchored in the outer membrane
      and has a broad specificity. AmiD is capable of cleaving the intact peptidoglycan
      (PG) as well as soluble fragments containing N-acetylmuramic acid regardless of
      the presence of an anhydro form or not, unlike the four other amidases, AmiA,
      AmiB, AmiC, and AmpD, which have some specificity. AmiD function is, however, not
      clearly established but it could be part of the enzymatic machinery involved in
      the PG turnover in E. coli. We solved three structures of the E. coli zinc
      amidase AmiD devoid of its lipidic anchorage: the holoenzyme, the apoenzyme in
      complex with the substrate anhydro-N-acetylmuramic-acid-L-Ala-gamma-d-Glu-L-Lys,
      and the holoenzyme in complex with the L-Ala-gamma-D-Glu-L-Lys peptide, the
      product of the hydrolysis of this substrate by AmiD. The AmiD structure shows a
      relatively flexible N-terminal extension that allows an easy reach of the PG by
      the enzyme inserted into the outer membrane. The C-terminal domain provides a
      potential extended geometrical complementarity to the substrate. AmiD shares a
      common fold with AmpD, the bacteriophage T7 lysozyme, and the PG recognition
      proteins, which are receptor proteins involved in the innate immune responses of
      a wide range of organisms. Analysis of the different structures reveals the
      similarity between the catalytic mechanism of zinc amidases of the AmiD family
      and the thermolysin-related zinc peptidases.

PMID- 20036253
TI  - Crystal structure of ArgP from Mycobacterium tuberculosis confirms two distinct
      conformations of full-length LysR transcriptional regulators and reveals its
      function in DNA binding and transcriptional regulation.
AB  - Mycobacterium tuberculosis presents a challenging medical problem partly due to
      its persistent nonreplicative state. The inhibitor of chromosomal replication
      (iciA) protein encoded by M. tuberculosis has been suggested to inhibit
      chromosome replication initiation in vitro. However, iciA has also been
      identified as arginine permease (ArgP), a regulatory transcription factor for
      arginine outward transport. In order to understand the function of ArgP, we have
      determined its crystal structure by X-ray crystallography to a resolution of 2.7
      A. ArgP is a member of the LysR-type transcriptional regulators (LTTRs) and forms
      a homodimer with each subunit containing two domains: a DNA binding domain (DBD)
      and a regulatory domain (RD). Two conformationally distinct subunits were
      identified: closed subunit and open subunit. This phenomenon was first observed
      in LTTR CbnR, but not in LTTR CrgA, and might be common in LTTRs. We identified
      two forms of dimers: DBD-type dimers and RD-type dimers. The former is confirmed
      in solution, and the latter is considered to form oligomers during function. We
      provide the first structural insights into the interaction of the extreme C
      terminal residues with the DBD, which is confirmed by mutagenesis and analytical
      ultracentrifugation to be important for stability of the functional dimer. The
      structure serves as a model to suggest how three critical aspects, namely, DNA
      binding, homo-oligomerization, and interaction with RNAP, are mediated during
      regulation processing. A model is proposed for the LysR family of dimeric
      regulators.

PMID- 20036254
TI  - Evolutionary optimization of computationally designed enzymes: Kemp eliminases of
      the KE07 series.
AB  - Understanding enzyme catalysis through the analysis of natural enzymes is a
      daunting challenge-their active sites are complex and combine numerous
      interactions and catalytic forces that are finely coordinated. Study of more
      rudimentary (wo)man-made enzymes provides a unique opportunity for better
      understanding of enzymatic catalysis. KE07, a computationally designed Kemp
      eliminase that employs a glutamate side chain as the catalytic base for the
      critical proton abstraction step and an apolar binding site to guide substrate
      binding, was optimized by seven rounds of random mutagenesis and selection,
      resulting in a >200-fold increase in catalytic efficiency. Here, we describe the
      directed evolution process in detail and the biophysical and crystallographic
      studies of the designed KE07 and its evolved variants. The optimization of KE07's
      activity to give a k(cat)/K(M) value of approximately 2600 s(-1) M(-1) and an
      approximately 10(6)-fold rate acceleration (k(cat)/k(uncat)) involved the
      incorporation of up to eight mutations. These mutations led to a marked decrease
      in the overall thermodynamic stability of the evolved KE07s and in the
      configurational stability of their active sites. We identified two primary
      contributions of the mutations to KE07's improved activity: (i) the introduction
      of new salt bridges to correct a mistake in the original design that placed a
      lysine for leaving-group protonation without consideration of its "quenching"
      interactions with the catalytic glutamate, and (ii) the tuning of the
      environment, the pK(a) of the catalytic base, and its interactions with the
      substrate through the evolution of a network of hydrogen bonds consisting of
      several charged residues surrounding the active site.

PMID- 20036255
TI  - Crystal structures of the CERT START domain with inhibitors provide insights into
      the mechanism of ceramide transfer.
AB  - The cytosolic protein CERT transfers ceramide from the endoplasmic reticulum to
      the Golgi apparatus where ceramide is converted to SM. The C-terminal START
      (steroidogenic acute regulatory protein-related lipid transfer) domain of CERT
      binds one ceramide molecule in its central amphiphilic cavity. (1R,3R)-N-(3
      Hydroxy-1-hydroxymethyl-3-phenylpropyl)alkanamide (HPA), a synthesized analogue
      of ceramide, inhibits ceramide transfer by CERT. Here we report crystal
      structures of the CERT START domain in complex with HPAs of varying acyl chain
      lengths. In these structures, one HPA molecule is buried in the amphiphilic
      cavity where the amide and hydroxyl groups of HPA form a hydrogen-bond network
      with specific amino acid residues. The Omega1 loop, which has been suggested to
      function as a gate of the cavity, adopts a different conformation when bound to
      HPA than when bound to ceramide. In the Omega1 loop region, Trp473 shows the
      largest difference between these two structures. This residue exists inside of
      the cavity in HPA-bound structures, while it is exposed to the outside of the
      protein in the apo-form and ceramide-bound complex structures. Surface plasmon
      resonance experiments confirmed that Trp473 is important for interaction with
      membranes. These results provide insights into not only the molecular mechanism
      of inhibition by HPAs but also possible mechanisms by which CERT interacts with
      ceramide.

PMID- 20036256
TI  - Backbone model of an aquareovirus virion by cryo-electron microscopy and
      bioinformatics.
AB  - Grass carp reovirus (GCRV) is a member of the aquareovirus genus in the
      Reoviridae family and has a capsid with two shells-a transcription-competent core
      surrounded by a coat. We report a near-atomic-resolution reconstruction of the
      GCRV virion by cryo-electron microscopy and single-particle reconstruction. A
      backbone model of the GCRV virion, including seven conformers of the five capsid
      proteins making up the 1500 molecules in both the core and the coat, was derived
      using cryo-electron microscopy density-map-constrained homology modeling and
      refinement. Our structure clearly showed that the amino-terminal segment of core
      protein VP3B forms an approximately 120-A-long alpha-helix-rich extension
      bridging across the icosahedral 2-fold-symmetry-related molecular interface. The
      presence of this unique structure across this interface and the lack of an
      external cementing molecule at this location in GCRV suggest a stabilizing role
      of this extended amino-terminal density. Moreover, part of this amino-terminal
      extension becomes invisible in the reconstruction of transcription-competent core
      particles, suggesting its involvement in endogenous viral RNA transcription. Our
      structure of the VP1 turret represents its open state, and comparison with its
      related structures at the closed state suggests hinge-like domain movements
      associated with the mRNA-capping machinery. Overall, this first backbone model of
      an aquareovirus virion provides a wealth of structural information for
      understanding the structural basis of GCRV assembly and transcription.

PMID- 20036258
TI  - pH-induced conformational change of the beta-barrel-forming protein OmpG
      reconstituted into native E. coli lipids.
AB  - A gating mechanism of the beta-barrel-forming outer membrane protein G (OmpG)
      from Escherichia coli was recently presented. The mechanism was based on X-ray
      structures revealed from crystals grown from solubilized OmpG at both neutral pH
      and acidic pH. To investigate whether these conformations represent the naturally
      occurring gating mechanism, we reconstituted OmpG in native E. coli lipids and
      applied high-resolution atomic force microscopy. The reconstituted OmpG molecules
      assembled into both monomers and dimers. Single monomeric and dimeric OmpG
      molecules showed open channel entrances at pH 7.5 and at room temperature. The
      extracellular loops connecting the beta-strands that form the transmembrane beta
      barrel pore exhibited elevated structural flexibility. Upon lowering the pH to
      5.0, the conformation of OmpG molecules changed to close the extracellular
      entrance of their channel. It appears that one or more of the extracellular loops
      collapsed onto the channel entrance. This conformational change was fully
      reversible. Our data confirm that the previously reported gating mechanism of
      OmpG occurs at physiological conditions in E. coli lipid membranes.

PMID- 20036257
TI  - Molecular and structural insight into proNGF engagement of p75NTR and sortilin.
AB  - Nerve growth factor (NGF) is initially synthesized as a precursor, proNGF, that
      is cleaved to release its C-terminal mature form. Recent studies suggested that
      proNGF is not an inactive precursor but acts as a signaling ligand distinct from
      its mature counterpart. proNGF and mature NGF initiate opposing biological
      responses by utilizing both distinct and shared receptor components. In this
      study, we carried out structural and biochemical characterization of proNGF
      interactions with p75NTR and sortilin. We crystallized proNGF complexed to p75NTR
      and present the structure at 3.75-A resolution. The structure reveals a 2:2
      symmetric binding mode, as compared with the asymmetric structure of a previously
      reported crystal structure of mature NGF complexed to p75NTR and the 2:2
      symmetric complex of neurotrophin-3 (NT-3) and p75NTR. Here, we discuss the
      possible origins and implications of the different stoichiometries. In the proNGF
      p75NTR complex, the pro regions of proNGF are mostly disordered and two hairpin
      loops (loop 2) at the top of the NGF dimer have undergone conformational changes
      in comparison with mature NT structures, suggesting possible interactions with
      the propeptide. We further explored the binding characteristics of proNGF to
      sortilin using surface plasmon resonance and cell-based assays and determined
      that calcium ions promote the formation of a stable ternary complex of proNGF
      sortilin-p75NTR. These results, together with those of previous structural and
      mechanistic studies of NT-receptor interactions, suggest the potential for
      distinct signaling activities through p75NTR mediated by different NT-induced
      conformational changes.

PMID- 20036259
TI  - Neutron diffraction studies of a class A beta-lactamase Toho-1 E166A/R274N/R276N
      triple mutant.
AB  - beta-Lactam antibiotics have been used effectively over several decades against
      many types of bacterial infectious diseases. However, the most common cause of
      resistance to the beta-lactam antibiotics is the production of beta-lactamase
      enzymes that inactivate beta-lactams by rapidly hydrolyzing the amide group of
      the beta-lactam ring. Specifically, the class A extended-spectrum beta-lactamases
      (ESBLs) and inhibitor-resistant enzymes arose that were capable of hydrolyzing
      penicillins and the expanded-spectrum cephalosporins and monobactams in resistant
      bacteria, which lead to treatment problems in many clinical settings. A more
      complete understanding of the mechanism of catalysis of these ESBL enzymes will
      impact current antibiotic drug discovery efforts. Here, we describe the neutron
      structure of the class A, CTX-M-type ESBL Toho-1 E166A/R274N/R276N triple mutant
      in its apo form, which is the first reported neutron structure of a beta
      lactamase enzyme. This neutron structure clearly reveals the active-site
      protonation states and hydrogen-bonding network of the apo Toho-1 ESBL prior to
      substrate binding and subsequent acylation. The protonation states of the active
      site residues Ser70, Lys73, Ser130, and Lys234 in this neutron structure are
      consistent with the prediction of a proton transfer pathway from Lys73 to Ser130
      that is likely dependent on the conformation of Lys73, which has been
      hypothesized to be coupled to the protonation state of Glu166 during the
      acylation reaction. Thus, this neutron structure is in agreement with a proposed
      mechanism for acylation that identifies Glu166 as the general base for catalysis.

PMID- 20036260
TI  - Naphtho[1,2-b]furan-4,5-dione inactivates EGFR and PI3K/Akt signaling pathways in
      human lung adenocarcinoma A549 cells.
AB  - AIMS: Naphtho[1,2-b]furan-4,5-dione (NFD), prepared from 2-hydroxy-1,4
      naphthoquinone and chloroacetaldehyde in an efficient one-pot reaction, exhibits
      an anti-carcinogenic effect. This study was performed to elucidate whether EGFR
      and PI3K signaling pathways are involved in NFD-induced apoptosis of human lung
      adenocarcinoma A549 cells. MAIN METHODS: The effect of NFD on cell viability and
      apoptosis was measured by the MTT assay and flow cytometry. The phosphorylation
      levels of EGFR and its regulatory molecules by NFD treatment were studied by
      immunoblots. KEY FINDINGS: Immunoblot showed that NFD inhibited EGFR
      phosphorylation and the activation of PI3K/Akt, downstream molecules of EGFR
      pathway, in A549 cells. The levels of downstream targets of Akt, including
      phospho-glycogen synthase kinase-3beta (p-GSK-3beta), GSK-3beta, forkhead
      transcription factor (FKHR), and cyclin D1, were also reduced after NFD
      treatment. Moreover, inactivation of nuclear factor-kappaB (NFkappaB), modulation
      of IkappaKalpha/beta and IkappaBalpha, up-regulation of Bad and Bax, and down
      regulation of anti-apoptotic proteins including phospho-Bad, Bcl-2, survivin, and
      XIAP were also found in NFD-treated cells. In addition, NFD treatment disrupted
      mitochondrial membrane potential (DeltaPsim) and resulted in release of
      mitochondrial cytochrome c and activation of both caspases-9 and caspase-3.
      SIGNIFICANCE: These findings indicate that EGFR and PI3K/Akt signaling pathways
      play important roles in NFD-induced apoptosis of A549 cells.

PMID- 20036262
TI  - Stem cell transplantation for neurometabolic and neurodegenerative diseases.
AB  - Over the last decade, the potential for therapeutic use of stem cell
      transplantation for cell replacement or as cellular vectors for gene delivery for
      neurometabolic and neurodegenerative diseases has received a great deal of
      interest. There has been substantial progress in our understanding of stem cell
      biology. Potential applications of cell-mediated therapy include direct cell
      replacement or protection and repair of the host nervous system. Given the
      complexities of the cellular organization of the nervous system, especially in
      diseased states, it seems that using stem cells as cellular vectors to prevent or
      ameliorate neurological disorders rather than cell replacement and the regrowth
      of damaged circuitry is more likely to succeed in the near term. Recent success
      in the treatment of lysosomal storage diseases with genetically modified stem
      cells support this notion. In Alzheimer's and Parkinson's diseases, stem cell
      therapy is at its early stages and data generated in animal models and clinical
      trials using other cell types suggest that a combination of gene and stem cell
      therapy may be an optimal therapeutic paradigm.

PMID- 20036261
TI  - Comparison of the peripheral mediator background of heat injury- and plantar
      incision-induced drop of the noxious heat threshold in the rat.
AB  - AIMS: Previously we described the drop of the noxious heat threshold in response
      to mild heat injury or plantar incision. While mild heat injury elicits an
      immediate and short-lasting thermal hyperalgesia, surgical incision leads to a
      delayed and sustained heat hyperalgesia. Only very few peripheral mediators of
      these phenomena have been identified. Therefore the present study aimed at
      comparing the peripheral mediator background of heat hyperalgesia evoked by mild
      heat injury or surgical incision. MAIN METHODS: Heat hyperalgesia was assessed by
      measuring the behavioural noxious heat threshold in conscious rats employing an
      increasing-temperature water bath. KEY FINDINGS: The heat threshold drop evoked
      by a mild heat injury and measured 10min afterwards was reduced by intraplantarly
      applied HOE 140, a bradykinin B(2) receptor antagonist, NDGA, a non-selective
      lipoxygenase inhibitor, L-NOARG, a non-selective nitric oxide synthase inhibitor,
      TNP-ATP, a P2X purinoceptor antagonist and AMG9810, an antagonist of the
      transient receptor potential vanilloid type 1 (TRPV1) receptor. The heat
      threshold drop evoked by plantar incision and measured 18h later was reduced by
      intraplantarly applied HOE 140, [des-Arg(10)]-HOE 140, a bradykinin B(1) receptor
      antagonist, L-NOARG, TNP-ATP and the TRPV1 receptor antagonist SB-366791.
      SIGNIFICANCE: Only small differences have been revealed between the examined
      peripheral mediators of the acute heat hyperalgesia evoked by mild heat injury
      and the sustained increase in heat responsiveness induced by surgical incision.
      The B(2) and B(1) bradykinin receptor, P2X purinoceptors, TRPV1 receptor, nitric
      oxide synthase and lipoxygenase(s) are involved in at least one of these
      hyperalgesia models.

PMID- 20036263
TI  - Mechanism of St. John's wort extract (STW3-VI) during chronic restraint stress is
      mediated by the interrelationship of the immune, oxidative defense, and
      neuroendocrine system.
AB  - Chronic stress is a contributing risk factor for the development of psychiatric
      illnesses such as anxiety and depression disorders. The aim of the present study
      was to evaluate the mechanisms of action of the standardized St. John's wort
      extract (STW3-VI; SJW) in a chronic restraint stress model. Markers of
      antioxidant capacity such as superoxide dismutase (SOD), glutathione peroxidase
      (GPx), and catalase (CAT) in the hippocampus and hypothalamus, and plasma levels
      of ACTH and corticosterone as well as the inflammatory markers IL-6 and TNF-alpha
      were determined in rats exposed to chronic restraint stress for 21 consecutive
      days. In addition, total body and relative organ weights as well as behavioral
      changes in the open field test were evaluated on the last day. The results show
      that stressed animals decreased in open field activity compared to unstressed
      animals, which could be reversed by fluoxetine (10mg/kg, p.o.) and SJW (125
      750mg/kg, p.o.) treatment. In addition, chronic restraint stress significantly
      decreased thymus and spleen indices in the stressed control group. However,
      treating stressed rats with fluoxetine or STW3-VI produced a significant and dose
      dependent increase in both thymus and spleen indices compared to stressed
      controls. Additionally, SJW and fluoxetine significantly reduced stress-induced
      increases in plasma ACTH and corticosterone levels. Furthermore, the
      administration of SJW significantly reduced the stress-induced increase in TNF
      alpha levels. Our data provide new evidence for the hypothesis that the mechanism
      of action of STW3-VI is mediated by the interrelationship between the immune,
      oxidative defense and neuroendocrine system.

PMID- 20036264
TI  - Decreased glutathione levels and altered antioxidant defense in an animal model
      of schizophrenia: long-term effects of perinatal phencyclidine administration.
AB  - Perinatal phencyclidine (PCP) administration to rodents represents one of the
      more compelling animal models of schizophrenia. There is evidence that decreased
      glutathione (GSH) levels and oxidative stress mediated through free radicals in
      the central nervous system are involved in the pathophysiology of this disease.
      Limited data are available on the role of free radicals in neurotoxicity induced
      by NMDA-receptor antagonists. The aim of this study was to elucidate the long
      term effects of perinatal phencyclidine administration on superoxide dismutase
      (SOD), catalase (CAT), gamma-glutamyl cisteine ligase (gamma-GCL), glutathione
      peroxidase (GPx), glutathione reductase (GR) and levels of lipid peroxides as
      well as GSH content. The Wistar rats were treated on the 2nd, 6th, 9th and 12th
      postnatal (PN) days with either phencyclidine (10mg/kg) or saline and sacrificed
      on PN70. The activities of antioxidant enzymes and level of lipid peroxides and
      GSH were determined in dorsolateral frontal cortex (dlFC), hippocampus, thalamus
      and caudate nucleus. Expression of SOD1 and SOD2 was determined by immunoblot.
      Region-specific changes of the measured parameters were observed. Decreased
      content of reduced GSH and altered activities of GR, GPx and SOD were determined
      in dlFC. In hippocampus, reduced GSH content and decreased activities of GPx and
      GR were accompanied with increased activity of gamma-GCL and increased level of
      lipid peroxides. gamma-GCL and GSH content were also decreased in caudate
      nucleus, while in thalamus major findings are increased levels of lipid peroxides
      and GR activity and decreased gamma-GCL activity. It can be concluded that
      perinatal PCP administration produces long-term alteration of antioxidant
      defense. Further studies are necessary in order to clarify role of redox
      dysregulation in the pathogenetic mechanism of schizophrenia.

PMID- 20036265
TI  - Deficits of reflexive attention induced by abduction of the eye.
AB  - Attention mediates access of sensory events to higher cognitive systems and can
      be driven by either top-down voluntary mechanisms or in a bottom-up, reflexive
      fashion by the sensory properties of a stimulus. The exact mechanisms underlying
      these different modes of attention are controversial, but both types of attention
      appear to be tightly coupled to the systems used for the control of eye
      movements. Indeed, recent data indicates that patients with opthalmoplegia
      (paralysis of the eyes) have difficulty voluntarily attending to locations to
      which saccades cannot be made (Craighero, Carta, & Fadiga, 2001) and
      experimentally induced opthalmoplegia disrupts voluntary attention in normal
      participants. However, the extent to which reflexive attention is mediated by the
      ability to make eye-movements in normal participants remains unclear. Here, we
      address this issue by investigating the effect of an experimentally induced
      opthalmoplegia on voluntary and reflexive attentional orienting during visual
      search. We observed that abducting the eye into the temporal hemifield elicited
      deficits of both voluntary and reflexive attention for targets that appeared
      beyond the oculomotor range. This result confirms the link between oculomotor
      control and voluntary attention observed in opthalmoplegic patients and
      demonstrates for the first time that reflexive attention is mediated by the
      ability to make eye-movements in normal participants.

PMID- 20036266
TI  - Compensatory mechanisms underlie intact task-switching performance in
      schizophrenia.
AB  - Individuals with schizophrenia tend to perform poorly on many measures of
      cognitive control. However, recent task-switching studies suggest that they show
      intact task-switching performance, despite the fact that the regions involved in
      task-switching are known to be structurally and functionally impaired in the
      disorder. Behavioral, event-related potential (ERP) and functional magnetic
      resonance imaging (fMRI) measures were used to compare the temporal and spatial
      dynamics of task-switching performance in individuals with schizophrenia and
      controls. Consistent with previous studies, reaction time (RT) switch cost and
      its reduction with anticipatory preparation did not differ between groups. There
      were also no group differences on cue-locked ERP components associated with
      anticipatory preparation processes. However, both stimulus- and response-locked
      ERPs were significantly disrupted in schizophrenia, suggesting difficulty with
      task-set implementation. fMRI analyses indicated that individuals with
      schizophrenia showed hyperactivity in the dorsolateral prefrontal cortex and
      posterior parietal cortex. RT-fMRI and ERP-fMRI associations suggested that
      individuals with schizophrenia employ compensatory mechanisms to overcome
      difficulties in task-set implementation and thereby achieve the same behavioral
      outcomes as controls.

PMID- 20036268
TI  - Visual mismatch negativity to irrelevant changes is sensitive to task-relevant
      changes.
AB  - Event-related potentials (ERPs) were measured in response to frequent (standard)
      and infrequent (deviant) task-irrelevant bar patterns. The constituent bars of
      the deviant patterns had either different orientation or different color than the
      bars of the standard. The task was the detection of either the orientation or the
      color change of a centrally presented shape. The deviant minus the standard ERP
      difference produced posterior negativity and was identified as visual mismatch
      negativity (vMMN). On the one hand, vMMN to orientation deviancy had smaller
      amplitude in the task demanding detection of the orientation change, and vMMN to
      color deviancy had smaller amplitude in the task demanding the color change. On
      the other hand, irrelevant deviancy influenced the task-performance. Reaction
      time (RT) to the orientation change of the target shape was longer in sequences
      with orientation change in the background, whereas RT to color change was longer
      in sequences with color change in the background. This interaction suggested that
      there was competition between the processing of irrelevant stimuli that share
      characteristics of task-related changes and target-related processing.

PMID- 20036267
TI  - Neurocognitive correlates of alexithymia in asymptomatic individuals with HIV.
AB  - Alexithymia, an impairment of affective and cognitive emotional processing, is
      often associated with human immunodeficiency virus (HIV) and may reflect effects
      of the virus on brain areas that are also important for multiple cognitive
      functions, such as the prefrontal and anterior cingulate cortices. We
      hypothesized that there would be a correlation between extent of alexithymia and
      cognitive performance associated with these brain areas, including attention,
      executive function, and visuospatial processing. Thirty-four asymptomatic HIV+
      participants and 34 matched healthy HIV- volunteers were administered the Toronto
      Alexithymia Scale, a series of neuropsychological tests, and measures of apathy,
      depression, and quality of life (QoL). The HIV+ participants had significantly
      higher levels of alexithymia, depression and apathy than the HIV- group. The
      extent of alexithymia and two of its processing components (Difficulty Describing
      Feelings [DDF] and Externally Oriented Thinking), but not depression, correlated
      with performance on measures of executive and visuospatial abilities, consistent
      with dysfunction of the frontostriatal circuits and their cortical projections.
      Apathy was related to alexithymia and two processing components (Difficulty
      Identifying Feelings and DDF) but to only one cognitive measure. The higher rate
      of alexithymia, as well as cognitive dysfunction, in HIV may be a consequence of
      the infection on the frontostriatal system and its cortical connections. Our
      findings also demonstrated a dissociation of apathy and alexithymia in HIV,
      pointing to overlapping but distinct neural substrates within frontostriatal
      circuits. Alexithymia correlated strongly with QoL ratings, underscoring the
      importance of assessment and treatment of HIV-associated emotional and cognitive
      processing deficits.

PMID- 20036269
TI  - Individual differences in social behavior predict amygdala response to fearful
      facial expressions in Williams syndrome.
AB  - Williams syndrome (WS) is a genetic condition often paired with abnormal social
      functioning and behavior. In particular, those with WS are characterized as being
      relatively hypersocial, overly emotional/empathic, and socially uninhibited or
      fearless. In addition, WS is associated with abnormal amygdala structure and
      function. Very little is known however about the relationship between specific
      social behaviors and altered amygdala function in WS. This study was designed to
      compare three models that relate abnormal social behavior with amygdala function
      in WS (indiscriminate sociability, emotional and empathic sociability and social
      fearlessness). We used a social behavior assessment procedure (Salk Institute
      Sociability Questionnaire), functional magnetic resonance imaging and an implicit
      emotion face processing task to test these models. Our findings provide support
      for a model of abnormal social fearlessness by showing that in WS, abnormal
      amygdala response to fear is paired with an increased tendency to approach
      strangers. Specifically, individuals with WS that exhibited less amygdala
      response to fearful facial expressions (compared to neutral) also exhibited an
      increased tendency to approach strangers. These findings contribute to our
      understanding of social and emotional functioning in neurodevelopmental
      conditions and provide evidence that in WS, amygdala response to fear modulates
      social behavior.

PMID- 20036270
TI  - Transcriptomics-based identification of developmental toxicants through their
      interference with cardiomyocyte differentiation of embryonic stem cells.
AB  - The embryonic stem cell test (EST) predicts developmental toxicity based on the
      inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The
      subjective endpoint, the long culture duration together with the undefined
      applicability domain and related predictivity need further improvement to
      facilitate implementation of the EST into regulatory strategies. These aspects
      may be improved by studying gene expression changes in the ESC differentiation
      cultures and their modulation by compound exposure using transcriptomics. Here,
      we tested the developmental toxicants monobutyl phthalate and 6
      aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte
      differentiation was assessed after 10 days of culture. RNA of solvent controls
      was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental
      toxicant-exposed cultures was collected after 24 and 96 h. Samples were
      hybridized to DNA microarrays, and 1355 genes were found differentially expressed
      among the unexposed experimental groups. These regulated genes were involved in
      differentiation-related processes, and Principal Component Analysis (PCA) based
      on these genes showed that the unexposed experimental groups appeared in
      chronological order in the PCA, which can therefore be regarded as a continuous
      representation of the differentiation track. The developmental-toxicant-exposed
      cultures appeared to deviate significantly from this differentiation track, which
      confirms the compound-modulating effects on the differentiation process. The
      incorporation of transcriptomics in the EST is expected to provide a more
      informative and improved endpoint in the EST as compared with morphology,
      allowing early detection of differentiation modulation. Furthermore, this
      approach may improve the definition of the applicability domain and predictivity
      of the EST.

PMID- 20036272
TI  - Impact of biomarker development on drug safety assessment.
AB  - Drug safety has always been a key aspect of drug development. Recently, the Vioxx
      case and several cases of serious adverse events being linked to high-profile
      products have increased the importance of drug safety, especially in the eyes of
      drug development companies and global regulatory agencies. Safety biomarkers are
      increasingly being seen as helping to provide the clarity, predictability, and
      certainty needed to gain confidence in decision making: early-stage projects can
      be stopped quicker, late-stage projects become less risky. Public and private
      organizations are investing heavily in terms of time, money and manpower on
      safety biomarker development. An illustrative and "door opening" safety biomarker
      success story is the recent recognition of kidney safety biomarkers for pre
      clinical and limited translational contexts by FDA and EMEA. This milestone
      achieved for kidney biomarkers and the "know how" acquired is being transferred
      to other organ toxicities, namely liver, heart, vascular system. New technologies
      and molecular-based approaches, i.e., molecular pathology as a complement to the
      classical toolbox, allow promising discoveries in the safety biomarker field.
      This review will focus on the utility and use of safety biomarkers all along drug
      development, highlighting the present gaps and opportunities identified in organ
      toxicity monitoring. A last part will be dedicated to safety biomarker
      development in general, from identification to diagnostic tests, using the kidney
      safety biomarkers success as an illustrative example.

PMID- 20036271
TI  - Arsenite induced poly(ADP-ribosyl)ation of tumor suppressor P53 in human skin
      keratinocytes as a possible mechanism for carcinogenesis associated with arsenic
      exposure.
AB  - Arsenite is an environmental pollutant. Exposure to inorganic arsenic in drinking
      water is associated with elevated cancer risk, especially in skin. Arsenite alone
      does not cause skin cancer in animals, but arsenite can enhance the
      carcinogenicity of solar UV. Arsenite is not a significant mutagen at non-toxic
      concentrations, but it enhances the mutagenicity of other carcinogens. The tumor
      suppressor protein P53 and nuclear enzyme PARP-1 are both key players in DNA
      damage response. This laboratory demonstrated earlier that in cells treated with
      arsenite, the P53-dependent increase in p21(WAF1/CIP1) expression, normally a
      block to cell cycle progression after DNA damage, is deficient. Here we show that
      although long-term exposure of human keratinocytes (HaCaT) to a nontoxic
      concentration (0.1 microM) of arsenite decreases the level of global protein
      poly(ADP-ribosyl)ation, it increases poly(ADP-ribosyl)ation of P53 protein and
      PARP-1 protein abundance. We also demonstrate that exposure to 0.1 microM
      arsenite depresses the constitutive expression of p21 mRNA and P21 protein in
      HaCaT cells. Poly(ADP-ribosyl)ation of P53 is reported to block its activation,
      DNA binding and its functioning as a transcription factor. Our results suggest
      that arsenite's interference with activation of P53 via poly(ADP-ribosyl)ation
      may play a role in the comutagenic and cocarcinogenic effects of arsenite.

PMID- 20036273
TI  - Induction of microvascular leakage and histamine release by promutoxin, an Arg49
      phospholipase A2.
AB  - It has been recognized that phospholipase A(2) (PLA(2)) is a crucial factor of
      snake venom induced inflammation. Recently, promutoxin, a novel member of minor
      subgroup of snake venom PLA(2) (R49 PLA(2)) has been characterized in our
      laboratory, but its roles in induction of inflammation remain uninvestigated.
      Using highly purified promutoxin, we found this enzymatically inactive PLA(2)
      provoked a dose-dependent increase in microvascular leakage in the skin of rats.
      Pretreatment of rats with compound 48/80 diminished promutoxin-induced skin
      reaction and reduced mast cell numbers in rats. Cyproheptadine, terfenadine,
      Ginkgolide B and heparin inhibited promutoxin elicited microvascular leakage when
      they were co-injected with the stimulus to rat skin. Moreover, promutoxin was
      found to induce histamine release from human colon, lung and tonsil mast cells,
      and both metabolic inhibitors and pertussis toxin were capable of inhibiting
      promutoxin elicited histamine release. Provocation of microvascular leakage and
      mast cell activation by promutoxin suggests further that snake venom induced
      inflammation is related to mast cell activation and certain anti-inflammatory
      drugs could be therapeutic effective in treating snake wound.

PMID- 20036274
TI  - Antivenomics and venom phenotyping: A marriage of convenience to address the
      performance and range of clinical use of antivenoms.
AB  - Toxins from the same protein family present in venoms from snakes belonging to
      different genera often share antigenic determinants. A practical consequence of
      this circumstance is that it might be possible to formulate on an immunologically
      sound basis a mixture of venoms for generating antivenoms against a wide range of
      species. A deep insight into the inter- and intraspecific variation of the
      antigenic constituents of venoms from snakes of different geographic origin
      represents the key for designing novel polyvalent pan-generic antivenoms. This
      review illustrates how proteomic protocols ('venomics' and 'antivenomics') can
      aid in assessing the crossreactivity of antivenoms against homologous and
      heterologous venoms, establishing thus the range of clinical application. Recent
      work showing how the knowledge of evolutionary trends along with venom
      phenotyping may have an impact in designing a mixture of venoms for immunization
      aimed to produce a pan-American anti-crotalic antivenom is discussed.

PMID- 20036275
TI  - Antigenic cross-reactivity and immunogenicity of Bothrops venoms from snakes of
      the Amazon region.
AB  - Snakebites are still a critical public health problem in developing countries or
      isolated areas. In Brazil, the North Region has a high distribution coefficient
      worsened by the significant number of eventually unreported cases, due to
      difficulties in access to health services, to the natural geographic barriers and
      the vast territory. In the Rio Negro area, the species Bothrops atrox, Bothrops
      brazili, Lachesis muta muta and Bothriopsis taeniata are thought to be the major
      species responsible for snakebites. The aim of this study was to qualitatively
      and quantitatively determine the antigenic cross-reactivity and expression of
      toxins and the immunogenicity of Bothrops venom species of the Amazon and to
      evaluate the general efficacy of the therapeutic sera. The in vivo assays
      demonstrated that the defibrinating activity of B. taeniata venom was absent but
      that the lethal and hemorrhagic properties were more intense than in the B. atrox
      venom. The results evidence venom variability among the two B. atrox populations
      from two distinct Amazonian regions, which may reveal a subjacent speciation
      process. The results point to new aspects that may guide the improvement of anti
      Bothropic therapeutic serum.

PMID- 20036276
TI  - Renal and cardiovascular effects of Bothrops marajoensis venom and phospholipase
      A2.
AB  - Bothrops marajoensis is found in the savannah of Marajo Island in the State of
      Para and regions of Amapa State, Brazil. The aim of the work was to study the
      renal and cardiovascular effects of the B. marajoensis venom and phospholipase
      A(2) (PLA(2)). The venom was fractionated by Protein Pack 5PW. N-terminal amino
      acid sequencing of sPLA(2) showed amino acid identity with other lysine K49
      sPLA(2)s of snake venom. B. marajoensis venom (30 microg/mL) decreased the
      perfusion pressure, renal vascular resistance, urinary flow, glomerular
      filtration rate and sodium tubular transport. PLA(2) did not change the renal
      parameters. The perfusion pressure of the mesenteric bed did not change after
      infusion of venom. In isolated heart, the venom decreased the force of
      contraction and increased PP but did not change coronary flow. In the arterial
      pressure, the venom and PLA(2) decreased mean arterial pressure and cardiac
      frequency. The presence of atrial flutter and late hyperpolarisation reversed,
      indicating QRS complex arrhythmia and dysfunction in atrial conduction. In
      conclusion, B. marajoensis venom and PLA(2) induce hypotension and bradycardia
      while simultaneously blocking electrical conduction in the heart. Moreover, the
      decrease in glomerular filtration rate, urinary flow and electrolyte transport
      demonstrates physiological changes to the renal system.

PMID- 20036277
TI  - Earl R. Stadtman.

PMID- 20036278
TI  - Variation in expression of membrane IgM, CD21 (CR2) and CD32 (Fcgamma RIIB) on
      bovine lymphocytes with age: a longitudinal study.
AB  - Typically, neonatal calves have poor active antibody responses to vaccination,
      attributed to immaturity of the neonatal immune system and suppressive effects of
      maternal (colostral) antibodies. Responses of naive B cells are regulated by
      ligation of opposing activating (CD21, membrane IgM [mIgM]) and inhibitory (CD32)
      receptors. Expression of these receptors on blood lymphocytes of 15 calves, from
      birth to 6 months of age, was investigated by three-colour flow cytometry.
      Although the absolute number of mIgM(+) B lymphocytes was low in calves under 6
      weeks, the intensity of mIgM expression per cell was significantly higher than
      for adults and >90% expressed both CD21 and CD32. The intensity of CD21
      expression in calves did not differ significantly from adults, whereas CD32
      expression was lower. Paradoxically, these findings suggest that responses of
      neonates should bias toward activation at the B cell level, warranting further
      investigation to reveal strategies for development of vaccines that are
      efficacious at an early age.

PMID- 20036279
TI  - Case report: Long-term cognitive sequelae of sarin exposure.
AB  - The long-term sequelae of acute sarin exposure are not well understood. The
      largest clinical cohort resulted from the 1994 and 1995 attacks in Japan.
      Observers noted mostly psychiatric sequelae, with a high prevalence of post
      traumatic stress disorder (PTSD). We describe neurocognitive findings that may
      represent sequelae of low-level sarin exposure in Iraq.

PMID- 20036280
TI  - Pseudomonas aeruginosa bacteremia secondary to fingerstick glucose monitoring.
AB  - Routine fingersticks for blood glucose monitoring are essential for the
      management of diabetic patients. However, the development of infections following
      fingersticks is a potential complication of blood glucose monitoring that has
      been reported in the literature. We describe a case of Pseudomonas aeruginosa
      bacteremia introduced during a routine fingerstick for blood glucose monitoring
      in a febrile neutropenic patient.

PMID- 20036281
TI  - First detection of the Anaplasma phagocytophilum groEL-A genotype in man.
AB  - OBJECTIVE: Human Granulocytic Anaplasmosis (HGA) is an emerging disease caused by
      the gram-negative bacterium Anaplasma phagocytophilum which is transmitted by
      ticks of the genus Ixodes ricinus. For molecular detection of the pathogen by
      PCR, a conserved portion of the groEL gene within the groESL operon is frequently
      used as a target. A single G/A polymorphism in this region allows to discriminate
      between two genotypes, groEL-G and groEL-A. METHODS: Total DNA from peripheral
      blood samples of two HGA patients was analysed by RealTime PCR, employing a
      protocol designed for genotyping groEL-G- and groEL-A variants of A.
      phagocytophilum. RESULTS: We confirmed two clinical cases of HGA by PCR; in one
      patient, and for the first time in a human host, the groEL-A variant was
      detected, in the other case the pathogen was recognised as the groEL-G variant,
      up to now representing the only genotype reported in man. CONCLUSIONS: It is
      documented that HGA infections can be caused by two A. phagocytophilum groEL
      genotypes. At present, the preference of the A. phagocytophilum groEL-G genotype
      in humans remains unclear, as we describe the first patient with HGA caused by
      the groEL-A variant. For a conclusive interpretation, more data from HGA patients
      will be required.

PMID- 20036282
TI  - High resolution stereoscopic volume visualization of the mouse arginine
      vasopressin system.
AB  - New imaging technologies have increased our capabilities to resolve three
      dimensional structures from microscopic samples. Laser-scanning confocal
      microscopy is particularly amenable to this task because it allows the researcher
      to optically section biological samples, creating three-dimensional image
      volumes. However, a number of problems arise when studying neural tissue samples.
      These include data set size, physical scanning restrictions, volume registration
      and display. To deal with these issues, we undertook large-scale confocal
      scanning microscopy in order to visualize neural networks spanning multiple
      tissue sections. We demonstrate a technique to create and visualize a three
      dimensional digital reconstruction of the hypothalamic arginine vasopressin
      neuroendocrine system in the male mouse. The generated three-dimensional data
      included a volume of tissue that measures 4.35 mm x 2.6 mm x 1.4mm with a voxel
      resolution of 1.2 microm. The dataset matrix included 3508 x 2072 x 700 pixels
      and was a composite of 19,600 optical sections. Once reconstructed into a single
      volume, the data is suitable for interactive stereoscopic projection.
      Stereoscopic imaging provides greater insight and understanding of spatial
      relationships in neural tissues' inherently three-dimensional structure. This
      technique provides a model approach for the development of data sets that can
      provide new and informative volume rendered views of brain structures. This study
      affirms the value of stereoscopic volume-based visualization in neuroscience
      research and education, and the feasibility of creating large-scale high
      resolution interactive three-dimensional reconstructions of neural tissue from
      microscopic imagery.

PMID- 20036283
TI  - Recording and online analysis of auditory steady state responses (ASSR) in
      Matlab.
AB  - Auditory steady state responses (ASSR) are a current research focus because of
      their potential use as a diagnostic tool. Research platforms are required to test
      user defined stimuli and algorithms for the analysis of electrophysiologic
      responses. Commercially available ASSR devices are not adequately flexible. To
      enable a larger group of scientists to pursue ASSR research, we introduce a cost
      efficient and flexible ASSR setup. ASSR recording and online analysis software in
      Matlab (The Mathworks, Inc.) was developed for a standard PC equipped with an
      external professional sound card, audiometric headphones, and an EEG biosignal
      preamplifier.

PMID- 20036284
TI  - Analyzing neurite outgrowth from explants by fitting ellipses.
AB  - The establishment of appropriate connectivity in the developing nervous system
      depends on many molecular guidance cues. A key method for studying the response
      of nerve fibers to such guidance cues is to culture explants of neural tissue in
      three-dimensional collagen gels. However, most previous analyses of the neurite
      outgrowth patterns from these explants have been very simple, often measuring
      only one or two parameters. Here we introduce a more sophisticated method for
      characterizing neurite outgrowth from explants, based on fitting an ellipse to
      the pattern of outgrowth. This provides 5 parameters describing the outgrowth: x
      and y position of the center of the ellipse, the elongation, the area and the
      tilt. We then apply this method to a large dataset of dorsal root ganglion
      explants grown in the presence of precisely controlled gradients of nerve growth
      factor. This analysis reveals a number of new features of these data. For
      instance, we find that it is the position of the center of the ellipse rather
      than the shape of the ellipse that is correlated with the strength of the
      gradient. Together these results show that ellipse-fitting of explant data can
      give new insights into the biological processes underlying neurite guidance by
      molecular cues.

PMID- 20036285
TI  - Differences in methodology, but not differences in viral strain, account for
      variable experimental outcomes in laboratories utilizing the cottontail rabbit
      papillomavirus model.
AB  - The cottontail rabbit papillomavirus (CRPV) animal model is used in several
      laboratories worldwide to investigate immunogenicity, carcinogenicity and life
      cycle aspects of papillomaviruses. It is the only animal model in which the full
      life cycle of the virus from initiation of infection to malignant progression can
      be studied. A major strength of the model is that the viral DNA is infectious.
      This feature allows for the study of mutant genomes without the need to create
      infectious mutant virus. Results from laboratory to laboratory have not always
      been consistent. Different laboratories use different methods for creating
      infections from DNA and it was postulated that the different challenge methods
      could play a role in the differential outcomes. Because different laboratories
      use different strains of CRPV, it was also desirable to test if the difference in
      CRPV genomes contributed to the differential outcomes. In this study, three of
      the CRPV strains used most widely (Washington B, Orth CRPV and Hershey CRPV) were
      cloned into PUC19; the E8 ATG ko mutants for each strain were also generated. We
      employed the infection technique reported previously in which scarification is
      done first and is followed with delivery of DNA by pipette 3 days later. The
      papilloma outgrowth generated by these three wild type constructs and their E8
      ATG ko mutants was compared. No significant difference was found among the three
      strains or their E8 ATG ko mutants. E8 ATG ko mutants induced significantly
      smaller but persistent papillomas when compared to their respective wild type
      CRPVs. The gene gun was also used to create infections with both Hershey CRPV DNA
      and the corresponding E8 ATG ko and was found to lead to less vigorous growth as
      well as some regressions. Further studies suggested that gene gun delivery might
      have induced an immune response which then resulted in compromised growth of
      papillomas. It was concluded that the E8 gene is not required for infection. We
      suggest that standardized infection methods should be used in laboratories so
      that inconsistencies in conclusions will be minimized.

PMID- 20036286
TI  - Development of a high-throughput assay for measuring serum neutralizing antibody
      against enterovirus 71.
AB  - Enterovirus 71 (EV71) is the main etiologic agent of hand, foot, and mouth
      disease (HFMD) and causes frequently severe neurological complications and
      mortality in young children. The serum neutralizing antibody response is the
      major indicator of EV71 infection and protective immunity. The current serum
      neutralization test based on inhibition of cytopathic effect (Nt-CPE) requires
      manual microscopic examination, which is time-consuming and labor-intensive. In
      this study, a high-throughput neutralization assay which employs enzyme
      immunoassay for detecting growth of EV71 in Rhabdomyosarcoma (RD) cells and
      measuring serum neutralizing antibody (Nt-EIA) against EV71 was developed. RD
      cells infected with 100 TCID(50) of EV71 for 36-42h had the best performance and
      were selected for Nt-EIA. One hundred and twenty human sera (59 negative sera, 61
      positive sera) were measured for EV71 neutralization antibody titers by Nt-CPE
      and Nt-EIA. Neutralization antibody titers against EV71 determined by Nt-EIA had
      a high sensitivity (100%), specificity (94.9%) and agreement (97.5%) by a
      qualitative comparison with Nt-CPE. In the quantitative comparison, the
      correlation coefficient between Nt-EIA and Nt-CPE was 0.91 after log
      transformation. Overall, the Nt-EIA is a suitable alternative assay for the
      quantitation of EV71 neutralizing antibody to EV71.

PMID- 20036287
TI  - Neuroendocrine markers are expressed in human mammary glands.
AB  - BACKGROUND: Regulatory peptides have previously been detected in epithelial cells
      of human mammary glands. As these peptides are produced by scattered
      neuroendocrine cells in the epithelium of other tissues the aim of this study was
      to investigate whether the mammary glands express molecular markers for
      neuroendocrine cells. MATERIAL AND METHODS: Specimens from 28 human mammary
      glands were retrieved. The distribution of immunoreactive cells was determined
      using immunohistochemistry with antibodies versus a set of endocrine markers
      including peptide hormones, chromogranins/secretogranins, vesicular monoamine
      transporters, synaptophysin, serotonin and synaptic vesicle protein 2. RESULTS:
      Cells of the luminal epithelium of ducts and lobules of human mammary glands
      expressed vesicular monoamine transporter 2 and chromogranin B, as well as the
      previously reported regulatory peptides obestatin, ghrelin, adrenomedullin and
      apelin. Using consecutive sections, it was revealed that the immunoreactivity
      patterns of the regulatory peptides and vesicular monoamine transporter 2 were
      similar. Interestingly, immunoreactivity for secretogranin II, secretogranin III
      and chromogranin B was identified in myoepithelial cells. No immunoreactivity was
      detected for chromogranin A or synaptophysin. CONCLUSION: Specific cells in the
      epithelium and myoepithelium of mammary glands express neuroendocrine markers
      suggesting that mammary glands may have neuroendocrine functions.

PMID- 20036288
TI  - Microtubules govern stress granule mobility and dynamics.
AB  - Stress granules (SGs) are ribonucleoprotein (RNP)-containing assemblies that are
      formed in the cytoplasm in response to stress. Previously, we demonstrated that
      microtubule depolymerization inhibited SG formation. Here, we show that arsenate
      induced SGs move throughout the cytoplasm in a microtubule-dependent manner, and
      microtubules are required for SG disassembly, but not for SG persistence.
      Analysis of SG movement revealed that SGs exhibited obstructed diffusion on an
      average, though sometimes SGs demonstrated rapid displacements. Microtubule
      depolymerization did not influence preformed SG number and size, but
      significantly reduced the average velocity of SG movement, the frequency of quick
      movement events, and the apparent diffusion coefficient of SGs. Actin filament
      disruption had no effect on the SG motility. In cycloheximide-treated cells SGs
      dissociated into constituent parts that then dissolved within the cytoplasm.
      Microtubule depolymerization inhibited cycloheximide-induced SG disassembly.
      However, microtubule depolymerization did not influence the dynamics of poly(A)
      binding protein (PABP) in SGs, according to FRAP results. We suggest that the
      increase of SG size is facilitated by the transport of smaller SGs along
      microtubules with subsequent fusion of them. At least some protein components of
      SGs can exchange with the cytoplasmic pool independently of microtubules.

PMID- 20036289
TI  - Cycle and gender-specific cerebral activation during a verb generation task using
      fMRI: comparison of women in different cycle phases, under oral contraception,
      and men.
AB  - Recent observations have revealed some evidence of the influence of sex and
      menstrual cycle on cognitive functions. In order to examine further differences
      depending on different phases of menstrual cycle, the use of oral contraception,
      and gender, fMRI during verb generation tests was performed in 12 female
      volunteers at menstrual phase and at luteal phase, 12 female volunteers under
      oral contraception, and in 12 men. Females under oral contraception compared to
      females in the menstrual or luteal phase revealed superior activation during verb
      generation in the right hemisphere; compared to menstrual phase in the superior
      temporal and in the luteal phase in the inferior frontal cortex. Two further
      significant activations were revealed comparing females in the luteal phase with
      males; for the females in the left inferior frontal and for the males in the left
      superior temporal cortex. Our results indicate that cerebral activity during a
      verb generation task differs between women during different phases of the
      menstrual cycle and men, between women under oral contraception and men, as well
      as between women with and without oral contraception.

PMID- 20036290
TI  - Musashi1 as a marker of reactive astrocytes after transient focal brain ischemia.
AB  - The synthesis of glial-fibrillary acidic protein (GFAP) or the re-expression of
      progenitor markers such as Nestin increases in reactive astrocytes after brain
      ischemia. We investigated the dynamics of reactive astrocytes after transient
      focal brain ischemia by examining the expression of Musashi1 (Msi1), an RNA
      binding protein and another marker of neural stem/progenitor cells. In ischemic
      striatum induced by middle cerebral artery occlusion (MCAO), an increase in Msi1
      immunoreactivity was observed from 2 days after MCAO, persisting until 14 days.
      The proliferation of Msi1-positive cells was observed from 4 days after MCAO and
      reached a peak at 7 days. These Msi1-positive cells were regarded as reactive
      astrocytes based on their co-expression with GFAP or Nestin and their morphology.
      Msi1-positive cells were located in the peri-infarct area in a region similar,
      but not identical, to that of Nestin-positive cells. The Msi1(+)Nestin(+) cells
      were located much closer to the ischemic core than the Msi1(+)Nestin(-) cells.
      The present study revealed that Msi1-expression, similar to Nestin, is induced
      after brain ischemia and may be involved in the reactivation of astrocytes,
      including their proliferation. However, the difference in the distributions of
      Msi1 and Nestin suggests that some of their features may differ in reactive
      astrocytes.

PMID- 20036291
TI  - Neuropilin 2 deficiency does not affect cortical neuronal viability in response
      to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.
AB  - Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct
      members of the class III secreted Semaphorin subfamily. NRP2 plays important
      roles in repulsive axon guidance, angiogenesis and vasculogenesis through
      partnering with co-receptors such as vascular endothelial growth factor receptors
      (VEGFRs) during development. Emerging evidence also suggests that NRP2
      contributes to injury response and environment changes in adult brains. In this
      study, we examined the contribution of NRP2 gene to cerebral ischemia-induced
      brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2
      expression does not affect the outcome of brain injury induced by transient
      occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature
      in terms of the middle cerebral artery anatomy and microvessel density in the
      cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and
      almost identical to those of the heterozygous (NRP2(+/-)) and wild type
      (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction
      of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not
      different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19,
      p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of
      deterioration of neurological functions after stroke compared with their NRP2(+/-
      and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant
      neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in
      NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in
      NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies
      demonstrated that despite of its critical role in neuronal guidance and vascular
      formation during development, NRP2 expression dose not affect adult brain
      response to cerebral ischemia.

PMID- 20036292
TI  - Analysis of rotavirus non-structural protein NSP5 by mass spectrometry reveals a
      complex phosphorylation pattern.
AB  - Genomic replication and partial assembly of Rotavirus takes place in cytoplasmic
      viral structures called viroplasms. NSP5 is a viral phosphoprotein localized in
      viroplasms and its expression is imperative for viral cycle progress. During
      infection three isoforms of NSP5 can be observed by SDS-PAGE (26, 28 and 33
      35kDa) and previous reports suggested that they differ in their phosphorylation
      patterns. In this study we obtained NSP5 from infected cells and by mass
      spectrometry we were able to identify nine phosphorylation sites. We detected
      that in all the isoforms the same residues can be found either phosphorylated or
      unmodified. Quantitative analysis showed that the 28kDa isoform has a higher
      phosphorylation level than the 26kDa isoform suggesting that migration properties
      depend on the total number of phosphorylated residues. Moreover, we identified
      two not previously described modifications for this protein: an N-acetylation in
      Serine-2 and an intramolecular disulfide bond in a highly conserved motif, CXXC
      which is located between two charged alpha-helix motifs.

PMID- 20036293
TI  - Therapeutic effect of PEGylated TNFR1-selective antagonistic mutant TNF in
      experimental autoimmune encephalomyelitis mice.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease, the
      pathogenesis of which is related to elevated serum levels of tumor necrosis
      factor-alpha (TNF). Although anti-TNF therapy has been tested as a potential
      treatment for MS, no remission of symptoms was observed. Recent reports indicated
      that the TNFR1 signal was responsible for the pathogenesis of murine experimental
      autoimmune encephalomyelitis (EAE), while the TNFR2 signal was responsible for
      recovery of the pathogenesis of EAE. Therefore, selective blocking of TNFR1
      appears to be a promising strategy for the treatment of MS. In this regard, we
      previously succeeded in developing a novel TNFR1-selective antagonistic TNF
      mutant (R1antTNF) by using phage display technology. Here, we have examined the
      therapeutic potential of R1antTNF using EAE mice. Treatment with PEGylated
      R1antTNF (PEG-R1antTNF) significantly improved the clinical score and cerebral
      demyelination at the onset of EAE. Considerable suppression of Th1 and Th17-type
      response was also observed in spleen and lymph node cells of mice given PEG
      R1antTNF. Moreover, the administration of PEG-R1antTNF suppressed the
      infiltration of inflammatory cells containing Th1 and Th17 cells into the spinal
      cord. These results suggest that selective blocking of TNFR1 by PEG-R1antTNF
      could be an effective therapeutic strategy against MS.

PMID- 20036294
TI  - Involvement of lysosomes in the early stages of axon degeneration.
AB  - Axon degeneration is a common hallmark of many neurodegenerative diseases, and
      the underlying mechanism remains largely unknown. Lysosomes are involved in some
      neurodegenerative diseases, including Alzheimer's disease and Parkinson's
      disease. Whether lysosomes are involved in axon degeneration is yet to be
      elucidated. In this study, we found only about 10% lysosomes remained in axons of
      cultured superior cervical ganglia (SCGs) after transection for 4h when stained
      with LysoTracker. Furthermore, we found that lysosomal disruption occurred
      earlier than morphological changes and loss of mitochondrial membrane potential.
      In addition, the well-known axon-protective protein Wld(S) delayed injury-induced
      axon degeneration from both morphological changes and lysosomal disruption.
      Lysosomal inhibitors including chloroquine and ammonium chloride induced axon
      degeneration in cultured SCGs, and Wld(S) also slowed down the axon degeneration
      induced by lysosomal inhibitors. All these data suggest that lysosomal disruption
      is an early marker of axon degeneration, and inhibition of lysosome induces axon
      degeneration in a Wld(S)-protectable way. Thus, maintenance of normal lysosomal
      function might be an important approach to delay axon degeneration in
      neurodegenerative diseases.

PMID- 20036297
TI  - WITHDRAWN: Common polymorphisms in the MDGA1 gene are associated with bipolar
      disorder and schizophrenia in the Chinese Han population.
AB  - This article has been withdrawn at the request of the authors. 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- 20036295
TI  - Improvement of dendritic-based vaccine efficacy against hepatitis B virus-related
      hepatocellular carcinoma by two tumor-associated antigen gene-infected dendritic
      cells.
AB  - Recently, studies on dendritic cell (DC) vaccine have focused on the development
      of more effective DC vaccine regimen, such as the application of multiple tumor
      associated antigen-targeted DC vaccine. This approach could be used to enhance
      efficacy of DC-based vaccine against tumors and infectious diseases. In this
      study, we analyzed whether DC from patients with hepatocellular carcinoma can be
      infected with the alpha-fetoprotein (AFP) gene and/or HBsAg gene (hepatocellular
      carcinoma-related antigen). Further, it was examined whether vaccination using
      these genetically engineered DC can induce stronger therapeutic antitumor
      immunity. Results revealed that DC infected with AdAFP (adenovirus AFP)/HBsAg can
      express AFP and HBsAg by reverse transcription-polymerase chain reaction and
      Western blot techniques. Compared with those before transfection, the expressions
      of membrane molecules increased dramatically. Specific T cells generated by DCs
      infected with AdAFP/HBsAg specifically recognized human leukocyte antigen-matched
      HepG2.2.15 cell lines. Moreover, the cytotoxic activity of cytotoxic T
      lymphocytes against HepG2.2.15 with DCs expressing AFP was significantly
      augmented by coinfection with the HBsAg gene. Administration with such vaccine
      also significantly increased the production of interleukin-12p70 and interferon
      gamma. Most importantly, in vivo results suggested that inhibitors of tumor
      growth were most significant in severe combined immunodeficiency mice model,
      which was treated with induced cytotoxic T lymphocyte by the AFP/HBsAg-DC
      vaccine. These results indicate that a vaccination therapy using DCs coinfected
      with the two tumor-associated antigen genes is an effective strategy for
      immunotherapy in the activation of DCs, CD4(+) T cells, and CD8(+) T cells, and
      may be useful in the clinical application of cancer vaccine therapy.

PMID- 20036298
TI  - Interaction of serotonin-related genes affects short-term antidepressant response
      in major depressive disorder.

PMID- 20036299
TI  - Evaluation of the acute oral toxicity class of tricentric chromium(III)
      propionate complex in rat.
AB  - Chromium(III) is an essential element for carbohydrate and lipid metabolism, and
      various chemical forms of this element are widely used in dietary supplements. Of
      particular interest is [Cr(3)O(O(2)CCH(2)CH(3))(6)(H(2)O)(3)](+) cation (CrProp),
      that has been proposed as an alternative source of Cr. However, its safety has
      not been studied completely. In this study, we evaluated the acute toxicity class
      of CrProp in Wistar rats applying the OECD 423 procedure. Male and female Wistar
      rats (n=12, 6 female symbol and 6 male symbol) were given by gavage either a
      single dose of CrProp 2000 mg kg(-1) body mass or equivalent volumes of distilled
      water, and fed Labofeed B diet, and observed carefully for 14 days, than
      sacrificed to collect samples for biochemical and histologic examination. No
      death cases were detected, no major abnormalities in animal behaviour, body mass
      gains, gross organ histology, and blood morphology, and biochemistry were
      observed, except some changes of liver mass and the activity of ALT in female
      rats. The results demonstrate that LD(50) of CrProp is greater than 2000 mg kg(
      1) when administrated orally to rat, thus this compound appears to be belong the
      fifth category in the GHS system or the fourth class ("unclassified") in the EU
      classification system.

PMID- 20036300
TI  - A search for hepatoprotective activity of aqueous extract of Rhus coriaria L.
      against oxidative stress cytotoxicity.
AB  - The protective effects of different concentrations of aqueous extract of Rhus
      coriaria L. fruit (75 and 100 microg/ml) and also gallic acid (100 microM) as one
      of its main components were examined against oxidative stress toxicity induced by
      cumene hydroperoxide (CHP) in isolated rat hepatocytes. Both extract
      concentrations and gallic acid (100 microM) significantly (P<0.05) protected the
      hepatocyte against all oxidative stress markers including cell lysis, ROS
      generation, lipid peroxidation, glutathione depletion, mitochondrial membrane
      potential decrease, lysosomal membrane oxidative damage and cellular proteolysis.
      Aqueous extracts of Rhus coriaria L. (75 and 100 microg/ml) were more effective
      than gallic acid (100 microM) in protecting hepatocytes against CHP induced lipid
      peroxidation (P<0.05). On the other hand gallic acid (100 microM) acted more
      effective than aqueous extracts of Rhus coriaria L. (75 and 100 microg/ml) at
      preventing hepatocyte membrane lysis (P<0.05). In addition H(2)O(2) scavenging
      effect of both extract concentrations (75 and 100 microg/ml) were determined in
      hepatocytes and compared with gallic acid (100 microM). Gallic acid (100 microM)
      was more effective than aqueous extracts of Rhus coriaria L. (75 and 100
      microg/ml) at H(2)O(2) scavenging activity (P<0.05).

PMID- 20036301
TI  - Protective effects of Forsythia suspensa extract against oxidative stress induced
      by diquat in rats.
AB  - Forsythia suspensa extract has been proved as a potential antioxidant in the
      recent years. The present study was undertaken to obtain the optimal antioxidant
      fraction in vitro and examine its antioxidative potential against diquat-induced
      oxidative stress in male Sprague Dawley rats in vivo. In vitro, 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free radical scavenging experiment indicated that the
      CH2Cl2 fraction of F. suspensa (FSC) exerted the strongest scavenging activities;
      forsythoside A, forythialan A and phillygenin from it might be the major
      antioxidant constituents. In vivo, pretreatment of rats with different doses of
      FSC (25, 50 and 100 mg/kg bw) and vitamin C (100 mg/kg bw, positive control) for
      15 days significantly lowered the tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in plasma compared to the
      negative control group. Also, FSC significantly increased the activities of
      superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of
      glutathione (GSH) in plasma, liver and kidney whereas it decreased the levels of
      malondialdehyde (MDA) in plasma and kidney. Moreover, the protective effect of
      FSC (100 mg/kg bw) was better than vitamin C. These results revealed that FSC
      exerted a protective effect against diquat-induced oxidative stress and is worthy
      of becoming a potential dietary antioxidant.

PMID- 20036302
TI  - Seasonal investigation of trace element contents in commercially valuable fish
      species from the Black sea, Turkey.
AB  - Fish species (Sarda sarda, Mulus barbatus ponticus, Trachurus trachurus and
      Merlangius merlangus) were collected from the Black sea, Turkey between 2008 and
      2009 (spring, summer, autumn and winter). The samples were analyzed using flame
      and graphite furnace atomic absorption spectrometry after microwave digestion.
      The maximum metal concentrations were found to be as 25.5-41.4 microg/g (Fe),
      17.8-25.7 microg/g (Zn), 0.28-0.64 microg/g (Pb), 0.64-0.99 microg/g (Cr), 1.3
      3.6 microg/g (Mn), 1.4-1.9 microg/g (Cu), 0.18-0.35 microg/g (Cd) and 0.25-0.42
      microg/g (Co) for fish species. The concentration of trace metals in samples is
      depended on fish species. Some species is accumulated trace metals at high ratio.
      Trace element levels in analyzed fish species were acceptable to human
      consumption at nutritional and toxic levels. The levels of lead and cadmium in
      fish samples were higher than the recommended legal limits.

PMID- 20036303
TI  - Antioxidant, free radical scavenging activities of Salvia brachyantha and its
      protective effect against oxidative cardiac cell injury.
AB  - In this study, antioxidant and free radical scavenging activities of an endemic
      Salvia species (Salvia brachyantha (Bordz) probed. was assessed in vitro using
      1,1-diphenyl-2-picryhydrazyl (DPPH) radical, beta-carotene linoleic acid,
      superoxide anion radical, hydroxyl radical, and reducing power assays. Regarding
      our data, the plant extract exhibited antioxidant and radical scavenging
      activities at different magnitudes of potency. In addition, this study was
      undertaken to assess whether methanol extract of S. brachyantha could increase
      the endogenous antioxidant enzymes in cells, and where such increased cellular
      defences could provide protection against oxidative cell injury. Pre treatment of
      rat heart cell lines with 100 microg/ml of plant extract for 24h significantly
      prevented cell damage and enhanced activity of antioxidant enzymes induced by a
      treatment with xanthine/xanthine oxidase. Increased reactive oxygen species and
      cell apoptosis induced by xanthine/xanthine oxidase was dose-dependently
      prevented when cells were pre treated for 24h with plant extract. These results
      indicated that S. brachyantha could protect against cell injury via induction of
      the antioxidant enzyme defences. The extract of this plant might be valuable
      antioxidant natural sources and seemed to be applicable in both healthy medicine
      and food industry.

PMID- 20036304
TI  - beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine
      oxidase (MAO).
AB  - Peganum harmala L. is a multipurpose medicinal plant increasingly used for
      psychoactive recreational purposes (Ayahuasca analog). Harmaline, harmine,
      harmalol, harmol and tetrahydroharmine were identified and quantified as the main
      beta-carboline alkaloids in P. harmala extracts. Seeds and roots contained the
      highest levels of alkaloids with low levels in stems and leaves, and absence in
      flowers. Harmine and harmaline accumulated in dry seeds at 4.3% and 5.6% (w/w),
      respectively, harmalol at 0.6%, and tetrahydroharmine at 0.1% (w/w). Roots
      contained harmine and harmol with 2.0% and 1.4% (w/w), respectively. Seed
      extracts were potent reversible and competitive inhibitors of human monoamine
      oxidase (MAO-A) with an IC(50) of 27 microg/l whereas root extracts strongly
      inhibited MAO-A with an IC(50) of 159 microg/l. In contrast, they were poor
      inhibitors of MAO-B. Inhibition of MAO-A by seed extracts was quantitatively
      attributed to harmaline and harmine whereas inhibition by root extracts came from
      harmine with no additional interferences. Stems and leaves extracts were poor
      inhibitors of MAO. The potent inhibition of MAO-A by seed and root extracts of P.
      harmala containing beta-carbolines should contribute to the psychopharmacological
      and toxicological effects of this plant and could be the basis for its purported
      antidepressant actions.

PMID- 20036305
TI  - HEMA reactivity with demineralized dentin.
AB  - OBJECTIVES: 2-Hydroxyethylmethacrylate (HEMA) was compared to its epoxy analogue,
      glycidoxypropylmethacrylate (GMA), for reactivity with 2,6-diaminohexanoic acid
      (Lysine), an amino acid present in collagen possessing a reactive amino side
      chain. The aim was to verify whether HEMA could chemically react with collagen
      fibers. METHODS: Capillary electrophoresis was used to analyse reaction products
      together with computer aided chemistry. Retention of HEMA in demineralized
      dentine particles was investigated by infrared spectroscopy. RESULTS: It was
      found by that HEMA does not form any new molecular species when contacted with
      lysine whereas GMA completely reacts to form the expected addition product.
      Computer aided chemistry confirmed this finding. Infrared spectroscopy showed
      that demineralized dentin has strong affinity for HEMA and retains this monomer
      despite extensive water washing. CONCLUSIONS: We interpret this behavior as
      demonstrating solvation of HEMA in the collagen polymer network.

PMID- 20036306
TI  - Protective effect of post-ischemic treatment with trans-resveratrol on cytokine
      production and neutrophil recruitment by rat liver.
AB  - Oxidative and inflammatory processes are elicited during hepatic post-ischemic
      reperfusion and generate liver damage. This study investigated the early anti
      inflammatory effect of trans-resveratrol (T-res) and its consequences on the late
      self-aggravating inflammatory process in liver ischemia-reperfusion (I/R).
      Partial hepatic ischemia was initiated in rats for 1 h and T-res (0.02 and 0.2
      mg/kg) was administered intravenously 5 min before starting reperfusion for 3 h.
      Plasma levels of aminotransferases and cytokines (tumour necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, IL-6) and hepatic neutrophil recruitment were
      assessed. Hepatic expression of stress protein (heat-shock protein (HSP-70), heme
      oxygenase-1(HO-1)) and cytokine (TNF-alpha, IL-1beta, keratinocyte
      chemoattractant (KC)) mRNA was investigated. I/R caused an increase in
      aminotransferase levels and increased polymorphonuclear cell infiltration. Post
      ischemic treatment with T-res (0.02 and 0.2 mg/kg) resulted in a significant
      decrease in aminotransferase, IL-1beta and IL-6 plasma levels by about 40%, 60%
      and 40%, respectively, compared to the vehicle I/R group. Post-ischemic treatment
      with T-res (0.02 mg/kg) also significantly decreased hepatic neutrophil
      recruitment. TNF-alpha, IL-1beta, KC and HO-1 hepatic mRNA expression was reduced
      by T-res without any change in HSP-70 mRNA. This T-res mediated decrease in early
      release of cytokines and neutrophil recruitment led to a reduction in the late
      inflammatory process. T-resveratrol might be useful in the prevention of
      inflammation secondary to hepatic surgery or liver transplantation.

PMID- 20036307
TI  - Which alkylglycerols from shark liver oil have anti-tumour activities?
AB  - Alkylglycerols (alkyl-Gro) are ether lipids abundant in shark liver oil (SLO),
      and oral SLO or alkyl-Gro mix from this source have several in vivo biological
      activities including stimulation of haematopoiesis an immunological defences, or
      anti-tumour and anti-metastasis activities in vivo. Composition of natural alkyl
      Gro mix contains several alkyl-Gro varying by chain length and unsaturation, and
      individual anti-tumour activity of each molecule present in natural mix remained
      unknown. We synthesized six prominent constituents of natural alkyl-Gro mix,
      namely 12:0, 14:0 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro. Using an in vivo
      model of grafted tumour in mice (3LL cells), we studied and compared the oral
      anti-tumour and anti-metastasis activities of each of these 6 alkyl-Gro. 16:1 and
      18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while
      saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Spleen
      weights at day 20 after graft were also measured and showed tremendous variations
      depending on the treatment. Tumour graft resulted in a raise in spleen weight in
      control group, this raise was nearly abolished in 16:1 and 18:1 alkyl-Gro-treated
      mice, and was reduced in 14:0 and 16:0 alkyl-Gro-treated mice. Conversely, 18:0
      alkyl-Gro-treated mice showed spleen weigh raise as compared with untreated
      grafted mice. These new data demonstrate a prominent role of unsaturation in the
      anti-tumour activities of alkyl-Gro.

PMID- 20036309
TI  - Sympathetic arousal moderates self-reported physiological arousal symptoms at
      baseline and physiological flexibility in response to a stressor in generalized
      anxiety disorder.
AB  - Compared to controls, individuals with generalized anxiety disorder (GAD) often
      fail to exhibit expected changes in physiological arousal in response to
      laboratory stressors. Nevertheless, individuals with GAD often report significant
      subjective arousal. We sought to assess the degree of sympathetic arousal in
      individuals with GAD and controls and the impact such arousal had on self
      reported physiological arousal and response to an emotional challenge. Degree of
      baseline sympathetic arousal moderated the self-report of physiological arousal
      in non-comorbid GAD at baseline such that within this group, higher levels of
      sympathetic arousal predicted reports of heightened physiological arousal
      compared to controls. Overall, individuals with GAD exhibited no significant
      changes in arousal in response to the emotional challenge. However, basal
      sympathetic arousal moderated degree of change such that non-comorbid GAD
      participants low in baseline sympathetic arousal exhibited changes in arousal
      similar to controls in response to the stressor. That basal sympathetic arousal
      moderated both self-reported arousal at baseline and sympathetic response to a
      stressor suggests important physiological heterogeneity in GAD, wherein only
      those individuals with heightened tonic sympathetic arousal report accompanying
      symptoms and display diminished sympathetic reactivity.

PMID- 20036310
TI  - Hard and soft micro- and nanofabrication: An integrated approach to hydrogel
      based biosensing and drug delivery.
AB  - We review efforts to produce microfabricated glucose sensors and closed-loop
      insulin delivery systems. These devices function due to the swelling and
      shrinking of glucose-sensitive microgels that are incorporated into silicon-based
      microdevices. The glucose response of the hydrogel is due to incorporated
      phenylboronic acid (PBA) side chains. It is shown that in the presence of
      glucose, these polymers alter their swelling properties, either by ionization or
      by formation of glucose-mediated reversible crosslinks. Swelling pressures
      impinge on microdevice structures, leading either to a change in resonant
      frequency of a microcircuit, or valving action. Potential areas for future
      development and improvement are described. Finally, an asymmetric nano
      microporous membrane, which may be integrated with the glucose-sensitive devices,
      is described. This membrane, formed using photolithography and block polymer
      assembly techniques, can be functionalized to enhance its biocompatibility and
      solute size selectivity. The work described here features the interplay of design
      considerations at the supramolecular, nano, and micro scales.

PMID- 20036311
TI  - Mouse germ cell development: from specification to sex determination.
AB  - Primordial germ cells (PGCs) are embryonic progenitors for the gametes. In the
      gastrulating mouse embryo, a small group of cells begin expressing a unique set
      of genes and so commit to the germline. Over the next 3-5 days, these PGCs
      migrate anteriorly and increase rapidly in number via mitotic division before
      colonizing the newly formed gonads. PGCs then express a different set of unique
      genes, their inherited epigenetic imprint is erased and an individual methylation
      imprint is established, and for female PGCs, the silent X chromosome is
      reactivated. At this point, germ cells (GCs) commit to either a female or male
      sexual lineage, denoted by meiosis entry and mitotic arrest, respectively. This
      developmental program is determined by cues emanating from the somatic
      environment.

PMID- 20036313
TI  - Effects of agents targeting glutamatergic systems on marble-burying behavior.
AB  - Accumulating evidence has implicated glutamatergic systems in psychiatric
      disorders. Abnormalities in glutamatergic systems have consistently been
      identified in obsessive-compulsive disorder (OCD). Marble-burying behavior has
      been described in literature as a potentially useful measure for modeling OCD in
      mice. However, involvement of glutamatergic systems in marble-burying behavior
      has largely remained unexplored. Here, the effects of an alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptor potentiator, CX546, and an NR2B
      subunit-containing N-methyl-D-aspartate (NMDA) receptor antagonist, Ro25-6981,
      were examined using a marble-burying test. Treatment with highest dose
      (30.0mg/kg) of CX546 significantly inhibited the marble-burying behavior.
      Moreover, treatment with Ro25-6981 also significantly reduced the marble-burying
      behavior. In contrast, both drugs did not affect locomotor activity in mice. The
      present results suggest that glutamatergic systems might be related to marble
      burying behavior. Furthermore, agents targeting glutamateric systems such as an
      AMPA receptor potentiator and an NR2B receptor antagonist, may be useful in
      treating OCD.

PMID- 20036312
TI  - New insights into the regulation of human cytotrophoblast cell differentiation.

PMID- 20036315
TI  - Aspirin-triggered lipoxin induces CB1-dependent catalepsy in mice.
AB  - Evidence are that inhibition of cyclooxygenase 2 (COX-2) enhances endocannabinoid
      signaling, indicating a crosstalk between these two eicosanoid pathways. Aspirin,
      a non-selective COX inhibitor, acetylates COX-2 with generation of a lipoxygenase
      (LOX) substrate, whose end product is the 15-epi-lipoxin A(4) (15-epi-LXA(4)), an
      aspirin-triggered lipoxin. Our objective was to investigate whether 15-epi-LXA(4)
      would potentiate in vivo effects of the endocannabinoid anandamide (AEA).
      Catalepsy was selected as a behavioral parameter and tested 5 min after AEA
      injection in all experiments. AEA induced dose-dependent (200 pmol/2 microl,
      i.c.v.) catalepsy. A sub-dose of AEA (10 pmol/2 microl, i.c.v.) was potentiated
      by aspirin (300 mg/kg, p.o.) via a 5-LOX-dependent step. The cataleptic effect
      induced by the interaction between sub-doses of 15-epi-LXA(4) (0.01 pmol/2
      microl, i.c.v.) and AEA (10 pmol/2 microl, i.c.v.) was prevented by the
      cannabinoid CB(1) receptors antagonist SR141716A (1mg/kg, i.p.), but not by the
      antagonist of lipoxin ALX receptors Boc-2 (10 microg/kg, i.p.). While previous
      studies have shown that COX inhibition itself may enhance endocannabinoid
      effects, here we add another piece of evidence revealing that a LOX-derivative
      produced in consequence of COX-2 acetylation participates in this process.

PMID- 20036314
TI  - Genomic and non-genomic actions of estrogen on synaptic plasticity in SH-SY5Y
      cells.
AB  - Estrogen modulates synaptic plasticity, an important mechanism of memory storage.
      Previously, we have reported that estrogen rapidly increases the expression of
      Arc (activity-regulated cytoskeleton associated protein), a key protein for
      synaptic plasticity, via non-genomic phosphoinositide-3 kinase (PI-3K)-, mitogen
      activated protein kinase (MAPK)-, and estrogen receptor (ER)-dependent pathways
      in SH-SY5Y cells. The present study aimed to investigate the role of each ER
      subtype, alpha and beta, in synaptic plasticity in SH-SY5Y cells. The specific
      agonist of ER beta (DPN) markedly induced Arc expression that mimics treatment
      with estrogen, but not ER alpha (PTT). Determination of subcellular localization
      of ER beta using immunocytochemistry shows that ER beta was retained in the
      cytoplasm of the untreated cells. In estrogen-treated cells, the membrane and
      cytosolic ER beta gradually decreased, while nuclear ER beta progressively
      increased in time-dependent manner, suggesting estrogen-dependent nuclear
      translocation of ER beta. Nuclear accumulation of ER beta at 6-12h post-estrogen
      treatment, leads to increased PSD-95 and SYP mRNA expression, indicating the
      classical genomic estrogenic action on synaptic plasticity. However, the block of
      PI-3K signaling by Wortmannin partially suppressed estrogen (48 h)-induced PSD-95
      and SYP expression, suggesting a crosstalk mechanism between genomic and non
      genomic actions of estrogen on synaptic plasticity. Therefore, the estrogen
      enhanced synaptic plasticity is ER beta-dependent and involves the crosstalk
      mechanism of non-genomic and genomic estrogenic actions.

PMID- 20036316
TI  - Coding sound direction in noisy environment in the superior colliculus of the
      rat.
AB  - The aim of the present study was to evaluate the effect of background noise on
      the directional sensitivity of neurons in the deep layers of the superior
      colliculus. Extra-cellular recordings were carried out in anaesthetized adult
      Long Evans rats. When stimulated in a noisy environment, most of the neurons
      remained sensitive to sound direction and only a few changed their optimal
      direction by more than 15 degrees. When stimulated at their optimal direction in
      the presence of background noise, a majority of neurons did not modify their
      response rate, whereas a limited proportion of neurons showed either a
      significant drop or facilitation of their response rate. Moreover, the neurons'
      receptive fields showed significant tuning modifications in the presence of
      background noise. In a noisy environment, the larger receptive fields became
      narrower, whereas the sharply tuned receptive fields got broader.

PMID- 20036308
TI  - Ionic storm in hypoxic/ischemic stress: can opioid receptors subside it?
AB  - Neurons in the mammalian central nervous system are extremely vulnerable to
      oxygen deprivation and blood supply insufficiency. Indeed, hypoxic/ischemic
      stress triggers multiple pathophysiological changes in the brain, forming the
      basis of hypoxic/ischemic encephalopathy. One of the initial and crucial events
      induced by hypoxia/ischemia is the disruption of ionic homeostasis characterized
      by enhanced K(+) efflux and Na(+)-, Ca(2+)- and Cl(-)-influx, which causes
      neuronal injury or even death. Recent data from our laboratory and those of
      others have shown that activation of opioid receptors, particularly delta-opioid
      receptors (DOR), is neuroprotective against hypoxic/ischemic insult. This
      protective mechanism may be one of the key factors that determine neuronal
      survival under hypoxic/ischemic condition. An important aspect of the DOR
      mediated neuroprotection is its action against hypoxic/ischemic disruption of
      ionic homeostasis. Specially, DOR signal inhibits Na(+) influx through the
      membrane and reduces the increase in intracellular Ca(2+), thus decreasing the
      excessive leakage of intracellular K(+). Such protection is dependent on a PKC
      dependent and PKA-independent signaling pathway. Furthermore, our novel
      exploration shows that DOR attenuates hypoxic/ischemic disruption of ionic
      homeostasis through the inhibitory regulation of Na(+) channels. In this review,
      we will first update current information regarding the process and features of
      hypoxic/ischemic disruption of ionic homeostasis and then discuss the opioid
      mediated regulation of ionic homeostasis, especially in hypoxic/ischemic
      condition, and the underlying mechanisms.

PMID- 20036317
TI  - Imipramine enhances cell proliferation and decreases neurodegeneration in the
      hippocampus after transient global cerebral ischemia in rats.
AB  - This study was aimed to determine whether imipramine chronic treatment promotes
      neurogenesis in the dentate gyrus (DG) and interferes with neuronal death in the
      CA1 subfield of the hippocampus after transient global cerebral ischemia (TGCI)
      in rats. After TGCI, animals were treated with imipramine (20mg/kg, i.p.) or
      saline during 14 days. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) was
      injected 24h after the last imipramine or saline injection to label proliferating
      cells. In order to confirm the effect of TGCI on neuronal death and cell
      proliferation, a group of animals was sacrificed 7 days after TGCI. Neurogenesis
      and neurodegeneration were evaluated by doublecortin (DCX)-immunohistochemistry
      and Fluoro-Jade C (FJC)-staining, respectively. The rate of cell proliferation
      increases 7 days but returns to basal levels 14 days after TGCI. There was a
      significant increase in the number of FJC-positive neurons in the CA1 of animals
      7 and 14 days after TGCI. Chronic imipramine treatment increased cell
      proliferation in the SGZ of DG and reduced the neurodegeneration in the CA1 of
      the hippocampus 14 days after TGCI. Immunohistochemistry for DCX detected an
      increased number of newly generated neurons in the hippocampal DG 14 days after
      TGCI, which was not affected by imipramine treatment. Further studies are needed
      to evaluate whether imipramine treatment for longer time would be able to promote
      survival of newly generated neurons as well as to improve functional recovery
      after TGCI.

PMID- 20036318
TI  - Neuroprotective properties of mildronate, a mitochondria-targeted small molecule.
AB  - Mildronate, a representative of the aza-butyrobetaine class of drugs with proven
      cardioprotective efficacy, was recently found to prevent dysfunction of complex I
      in rat liver mitochondria. The present study demonstrates that mildronate also
      acts as a neuroprotective agent. In a mouse model of azidothymidine (anti-HIV
      drug) neurotoxicity, mildronate reduced the azidothymidine-induced alterations in
      mouse brain tissue: it normalized the increase in caspase-3, cellular apoptosis
      susceptibility protein (CAS) and iNOS expression assessed by quantitative and
      semi-quantitative analysis. Mildronate also normalized the changes in cytochrome
      c oxidase (COX) expression, reduced the expression of glial fibrillary acidic
      protein (GFAP) and cellular infiltration. The present results show that the
      neuroprotective action of mildronate results at least partially from anti
      neurodegenerative (anti-apoptotic) and anti-inflammatory mechanisms. It might be
      suggested that the molecular conformation of mildronate can facilitate its easy
      binding to mitochondria, and regulate the expression of different signal
      molecules, hence maintaining cellular signaling and survival.

PMID- 20036319
TI  - Residual factor VIII-like cofactor activity of thioredoxin and related
      oxidoreductases.
AB  - BACKGROUND: Factor VIII is the cofactor for Factor X activation by Factor IXa.
      Activated Factor X, Factor Xa, in turn activates prothrombin in a sequence that
      leads to fibrin clot formation at the site of vascular injury. Although the
      biochemistry of the cascade has been well studied, the molecular mechanism
      underlying the cofactor role of Factor VIII is not understood. METHODS: We
      screened a bacterial peptide display library with Factor IXa and Factor X co
      immobilized on tosylactivated Dynabeads which were then used as platelet
      surrogates. Validation of peptide selection procedure and comparison of Factor
      VIII-like cofactor activity of oxidoreductases was performed using COATEST
      assays. Determination of Factor VIII as a folding catalyst with potential
      disulphide isomerase activity was determined using the RNase A renaturation
      assay. RESULTS: We set out to identify the cofactor requirements of the Factor
      IXa/Factor X procoagulant complex by random peptide display, and isolated a
      peptide with the active-site sequence, CGPC, of thioredoxin. This peptide was
      able to activate Factor X in a Factor IXa-dependent manner. Redox catalysts or
      oxidoreductases with homologous active-site vicinal cysteines such as PDI and
      DsbA also mimicked Factor VIII in their requirement of Factor IXa in Factor X
      activation. However, the cofactor activity of these peptides was up to a 1000
      fold lower than that of Factor VIII and they were therefore unable to catalyse
      blood coagulation. Factor X activation by PDI and by Factor VIII was abolished by
      oxidation in an isolated system, which implies a possible role for thiol
      disulphide exchange in the activity of the tenase complex. Using scrambled RNase
      A as a surrogate substrate, we also found that Factor VIII could renature this
      enzyme. CONCLUSION: Our findings suggest that Factor VIII may be a specialized
      folding catalyst with disulphide isomerase activity. We suggest that it is this
      activity that may underlie its cofactor function in Factor X activation, and that
      this function is interchangeable with classical oxidoreductases. GENERAL
      SIGNIFICANCE: The possible involvement of thiol-disulphide interchange as a
      mechanism underlying Factor VIII cofactor activity may provide some insight into
      the biochemistry of the intrinsic tenase complex.

PMID- 20036320
TI  - Novel neuronal proteolipid protein isoforms encoded by the human myelin
      proteolipid protein 1 gene.
AB  - The human myelin proteolipid protein 1 gene (hPLP1), which encodes the major
      structural myelin proteins of the central nervous system (CNS), is classically
      described as expressed in the oligodendrocytes, the CNS myelinating cells. We
      identified two new exons in the intron 1 of the hPLP1 gene that lead to the
      expression of additional mRNA and protein isoforms mainly expressed in neurons
      instead of oligodendrocytes. Those novel neuronal PLP isoforms are detected as
      soon as human fetal development and their concomitant expression is specific of
      the human species. As classical PLP proteins, the novel protein isoforms seem to
      be addressed to the plasma membrane. These results suggest for the first time
      that PLP may have functions in humans not only in oligodendrocytes but also in
      neurons and could be implicated in axono-glial communication. Moreover, this
      neuronal expression of the hPLP1 gene might explain the neuronal dysfunctions in
      patients carrying hPLP1 gene mutations.

PMID- 20036321
TI  - Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and
      nitric oxide in activated microglia.
AB  - Microglial activation has been implicated as one of the causative factors for
      neuroinflammation in various neurodegenerative diseases. The sphingolipid
      metabolic pathway plays an important role in inflammation, cell proliferation,
      survival, chemotaxis, and immunity in peripheral macrophages. In this study, we
      demonstrate that sphingosine kinase1 (SphK1), a key enzyme of the sphingolipid
      metabolic pathway, and its receptors are expressed in the mouse BV2 microglial
      cells and SphK1 alters the expression and production of proinflammatory cytokines
      and nitric oxide in microglia treated with lipopolysaccharide (LPS). LPS
      treatment increased the SphK1 mRNA and protein expression in microglia as
      revealed by the RT-PCR, Western blot and immunofluorescence. Suppression of SphK1
      by its inhibitor, N, N Dimethylsphingosine (DMS), or siRNA resulted in decreased
      mRNA expression of TNF-alpha, IL-1beta, and iNOS and release of TNF-alpha and
      nitric oxide (NO) in LPS-activated microglia. Moreover, addition of sphingosine 1
      phosphate (S1P), a breakdown product of sphingolipid metabolism, increased the
      expression levels of TNF-alpha, IL-1beta and iNOS and production of TNF-alpha and
      NO in activated microglia. Hence to summarize, suppression of SphK1 in activated
      microglia inhibits the production of proinflammatory cytokines and NO and the
      addition of exogenous S1P to activated microglia enhances their inflammatory
      responses. Since the chronic proinflammatory cytokine production by microglia has
      been implicated in neuroinflammation, modulation of SphK1 and S1P in microglia
      could be looked upon as a future potential therapeutic method in the control of
      neuroinflammation in neurodegenerative diseases.

PMID- 20036322
TI  - Lutein and docosahexaenoic acid prevent cortex lipid peroxidation in
      streptozotocin-induced diabetic rat cerebral cortex.
AB  - The mechanisms underlying diabetic encephalopathy, are largely unknown. Here, we
      examined whether docosahexaenoic acid (DHA) and lutein could attenuate the
      oxidative changes of the diabetic cerebral cortex. The levels of malondialdehyde
      (MDA) were significantly increased and glutathione (GSH) and glutathione
      peroxidase activity (GPx) were decreased in diabetic rats. The number of 4
      hydroxynonenal (4-HNE) positive cells was increased. Treatment with insulin,
      lutein or DHA and the combination of each antioxidant with insulin, significantly
      restored all markers concentrations mentioned above, and the increase in 4-HNE
      inmunofluorescence. We combined 4-HNE immunofluorescence with NeuN (Neuronal
      Nuclei) staining. The latter demonstrated extensive overlap with the 4-HNE
      staining in the cortex from diabetic rats. Our findings demonstrate a clear
      participation of glucose-induced oxidative stress in the diabetic encephalopathy,
      and that the cells suffering oxidative stress are neurons. Lowering oxidative
      stress through the administration of different antioxidants may be beneficial for
      the central nervous tissue in diabetes.

PMID- 20036323
TI  - Evolutionary and biochemical differences between human and monkey acidic
      mammalian chitinases.
AB  - Acidic mammalian chitinase (AMCase), an enzyme implicated in the pathology of
      asthma, is capable of chitin cleavage at a low pH optimum. The corresponding gene
      (CHIA) can be found in genome databases of a variety of mammals, but the enzyme
      properties of only the human and mouse proteins were extensively studied. We
      wanted to compare enzymes of closely related species, such as humans and
      macaques. In our attempt to study macaque AMCase, we searched for CHIA-like genes
      in human and macaque genomes. We found that both genomes contain several
      additional CHIA-like sequences. In humans, CHIA-L1 (hCHIA-L1) is an apparent
      pseudogene and has the highest homology to CHIA. To determine which of the two
      genes is functional in monkeys, we assessed their tissue expression levels. In
      our experiments, CHIA-L1 expression was not detected in human stomach tissue,
      while CHIA was expressed at high levels. However, in the cynomolgus macaque
      stomach tissue, the expression pattern of these two genes was reversed: CHIA-L1
      was expressed at high levels and CHIA was undetectable. We hypothesized that in
      macaques CHIA-L1 (mCHIA-L1), and not CHIA, is a gene encoding an acidic
      chitinase, and cloned it, using the sequence of human CHIA-L1 as a guide for the
      primer design. We named the new enzyme MACase (Macaca Acidic Chitinase) to
      emphasize its differences from AMCase. MACase shares a similar tissue expression
      pattern and pH optimum with human AMCase, but is 50 times more active in our
      enzymatic activity assay. DNA sequence of the mCHIA-L1 has higher percentage
      identity to the human pseudogene hCHIA-L1 (91.7%) than to hCHIA (84%). Our
      results suggest alternate evolutionary paths for human and monkey acidic
      chitinases.

PMID- 20036324
TI  - Effects of a chronic exposure to a highly palatable diet and its withdrawal, in
      adulthood, on cerebral Na+,K+-ATPase and plasma S100B in neonatally handled rats.
AB  - We have previously demonstrated that early environment influences the metabolic
      response, affecting abdominal fat deposition in adult female rats exposed to a
      long-term highly caloric diet. In the present study, our goal was to verify the
      effects of the chronic exposure, in adulthood, to a highly palatable diet
      (chocolate) on cerebral Na+,K+-ATPase activity and S100B protein concentrations,
      and the response to its withdrawal in neonatally handled and non-handled rats. We
      measured the consumption of foods (standard lab chow and chocolate), body weight
      gain, S100B protein concentrations, as well as cerebral Na(+),K(+)-ATPase
      activity during chronic exposure and after chocolate withdrawal in adult female
      rats that had been exposed or not to neonatal handling (10 min/day, 10 first days
      of life). Non-handled rats chronically exposed to chocolate exhibited increased
      plasma S100B levels, but there was no difference in abdominal fat S100B
      concentration between groups. Chronic chocolate consumption decreased Na+,K+
      ATPase activity in both amygdala and hippocampus in non-handled, but not in
      handled rats, and this effect disappeared after chocolate withdrawal. Non-handled
      animals also demonstrated increased frequency of head shaking in the open field
      after 24h of chocolate withdrawal in comparison to handled ones. These findings
      suggest that neonatal handling modifies the vulnerability to metabolic and brain
      alterations induced by chronic exposure to a highly palatable diet in adulthood.

PMID- 20036325
TI  - Calcium and zinc supplementation protects lead (Pb)-induced perturbations in
      antioxidant enzymes and lipid peroxidation in developing mouse brain.
AB  - Several studies have implicated oxidative stress as one of the important
      mechanisms of toxic effects of lead (Pb). In the present study we tested the
      beneficial effects of calcium (Ca2+) and zinc (Zn2+) in protecting the Pb-induced
      oxidative stress in the brains of developing and adult mice. Mice were
      lactationally exposed to 0.2% Pb and supplemented with either calcium (Ca2+) or
      zinc (Zn2+) and the mitochondrial antioxidant enzymes [superoxide dismutase
      (SOD), xanthine oxidase (XO) and catalase (CAT)] and lipid peroxidation (LP) were
      analyzed in cortex, hippocampus, cerebellum and medulla of brains excised on
      postnatal day (PND) 14, 21, 28 and 3 months. The levels of free radicals were
      measured using direct Electron Paramagnetic Resonance (EPR) spectroscopy.
      Exposure to Pb resulted a significant decrease in the activities of SOD, XO and
      CAT while the LP levels were significantly increased in different brain regions.
      Evaluation of EPR signals and g-values showed abundant accumulation of free
      radicals in different regions of the brain following Pb exposure. Interestingly
      the supplementation with Ca2+ or Zn2+ reversed the Pb-induced effects on
      antioxidant enzymes, LP and free radical formation; however Zn2+ supplementation
      appeared to be more protective. These findings strongly support that zinc and
      calcium supplementation significantly protect the Pb-induced oxidative stress, a
      major contributing factor to neurotoxicity.

PMID- 20036326
TI  - Prenatal diclofenac sodium administration increases the number of Purkinje cells
      in female rats: a stereological study.
AB  - Diclofenac sodium (DS) may affect the number of Purkinje cells in the developing
      cerebellum since DS can easily be transported from the maternal to the fetal
      physiological system during the pregnancy. In the present study, the effects of
      prenatal exposure to DS on the number of Purkinje cells in the cerebellum of 4
      week-old (4W-old) and 20-week-old (20W-old) female rats were investigated. There
      were two main groups: the drug-treated group (DTG) and the control group (CG).
      Beginning from the 5th day after mating for a period of 15 days, a daily dose of
      1 mg/kg of DS (Voltaren, 75 mg/3 ml ampul, Novartis, Mefar Ilac Sanayi A.S.,
      Kartal, Istanbul, Turkey) was intraperitoneally injected in the DTG of pregnant
      rats. In contrast, a daily dose of 1 ml/kg of isotonic saline was
      intraperitoneally administered to the CG of pregnant rats during the same period.
      After spontaneous delivery, female offspring were obtained, and the main groups'
      offspring were divided into two subgroups as a 4W-old group and a 20W-old group.
      Therefore, there were four groups at the end of the experiment: the 4W-old DTG
      and the CG, and the 20W-old DTG and the CG. At the end of 4W and 20W, offspring
      were perfused, their brains were dissected, and the number of cells estimated via
      the optical fractionator technique. Our results showed that while the total
      number of Purkinje cells in the cerebellum of offspring of DT 20W-old female rats
      was significantly higher than that of the CG, there was no significant difference
      between the 4W-old DTG and the control groups. Therefore, it could be suggested
      that DS administration during the prenatal period increases the number of
      Purkinje cells in the cerebellum of a developing female rat throughout postnatal
      20W.

PMID- 20036329
TI  - Detection of the misuse of steroids in doping control.
AB  - The list of prohibited substances of the World Anti-Doping Agency (WADA)
      classifies the administration of several steroids in sports as doping. Their
      analysis is generally performed using urine specimen as matrix. Lots of the
      steroids are extensively metabolised in the human body. Thus, knowledge of
      urinary excretion is extremely important for the sensitive detection of steroid
      misuse in doping control. The methods routinely used in steroid screening mainly
      focus on substances, that are excreted unconjugated or as glucuronides. Common
      procedures include deconjugation using a beta-glucuronidase enzyme. Following
      extraction and concentration the analytes are submitted to LC-MS(/MS) analysis
      and/or GC-MS(/MS) analyses. Besides the classical steroids, more and more
      products appear on the market for "dietary supplements" containing steroids that
      have never been marketed as approved drugs, mostly without proper labelling of
      the contents. To cover the whole range of potential products comprehensive
      screening tools have to be utilised in addition to the classical methods.
      Endogenous steroids, e.g. testosterone, represent a special group of compounds.
      As classical chemical methodology is incapable of discriminating synthetic
      hormones from the biosynthesised congeners, the method of steroid profiling is
      used for screening purpose. Additionally, based on isotope signatures a
      discrimination of synthetic and natural hormones can be achieved.

PMID- 20036328
TI  - Aldo-keto reductase 1C3 expression in MCF-7 cells reveals roles in steroid
      hormone and prostaglandin metabolism that may explain its over-expression in
      breast cancer.
AB  - Aldo-keto reductase (AKR) 1C3 (type 5 17beta-hydroxysteroid dehydrogenase and
      prostaglandin F synthase), may stimulate proliferation via steroid hormone and
      prostaglandin (PG) metabolism in the breast. Purified recombinant AKR1C3 reduces
      PGD(2) to 9alpha,11beta-PGF(2), Delta(4)-androstenedione to testosterone,
      progesterone to 20alpha-hydroxyprogesterone, and to a lesser extent, estrone to
      17beta-estradiol. We established MCF-7 cells that stably express AKR1C3 (MCF-7
      AKR1C3 cells) to model its over-expression in breast cancer. AKR1C3 expression
      increased steroid conversion by MCF-7 cells, leading to a pro-estrogenic state.
      Unexpectedly, estrone was reduced fastest by MCF-7-AKR1C3 cells when compared to
      other substrates at 0.1muM. MCF-7-AKR1C3 cells proliferated three times faster
      than parental cells in response to estrone and 17beta-estradiol. AKR1C3 therefore
      represents a potential target for attenuating estrogen receptor alpha induced
      proliferation. MCF-7-AKR1C3 cells also reduced PGD(2), limiting its dehydration
      to form PGJ(2) products. The AKR1C3 product was confirmed as 9alpha,11beta-PGF(2)
      and quantified with a stereospecific stable isotope dilution liquid
      chromatography-mass spectrometry method. This method will allow the examination
      of the role of AKR1C3 in endogenous prostaglandin formation in response to
      inflammatory stimuli. Expression of AKR1C3 reduced the anti-proliferative effects
      of PGD(2) on MCF-7 cells, suggesting that AKR1C3 limits peroxisome proliferator
      activated receptor gamma (PPARgamma) signaling by reducing formation of 15-deoxy
      Delta(12,14)-PGJ(2) (15dPGJ(2)).

PMID- 20036330
TI  - Concomitant modulation of transcripts related to fiber type determination and
      energy metabolism in skeletal muscle of female ovariectomized mice by estradiol
      injection.
AB  - In postmenopausal women, prevalence of metabolic syndrome (MS) is 40%. Aging is
      associated with a decline in basal metabolic rate and an alteration in tissue
      metabolism, leading to MS. Hormonal therapy has been shown to be effective
      against some of the MS-related features but its effects on sarcopenia and
      skeletal muscle metabolism remain unclear. We have analyzed the effects of
      estradiol (E(2)) on global gene expression in skeletal muscle of ovariectomized
      (OVX) female C57BL6 mice using the serial analysis of gene expression method.
      Animals were randomly assigned to six groups of each 14 mice: the vehicle group
      (OVX), and five groups in which E(2) was injected 1h, 3h, 6h, 18 h or 24h prior
      to sacrifice. E(2) modulated 177 transcripts, including 11 partially
      characterized transcripts and 52 potentially novel transcripts. Most of the
      differentially expressed transcripts were up-regulated at E(2)3h and E(2)18 h,
      while down-regulated transcripts were observed at E(2)6h and E(2)24h,
      illustrating two cycles of up and down E(2)-responsive genes. Modulated
      transcripts were involved in skeletal muscle structure/growth, fiber type
      distribution and energy metabolism. These results suggest that a single
      physiological dose of E(2) can concomitantly modulate transcripts determining
      skeletal muscle type and energy metabolism, which may in turn affect sarcopenia
      and MS.

PMID- 20036331
TI  - Steroid measurement with LC-MS/MS. Application examples in pediatrics.
AB  - The correct measurement of steroids is vital for the diagnosis of congenital
      adrenal hyperplasia (CAH), apparent mineralocorticoid excess, familial
      hyperaldosteronism type I, primary aldosteronism, Cushing's disease, adrenal
      insufficiency, etc. Steroid diagnostics also plays an important role in disorders
      of sexual differentiation and gonadal function. Steroid metabolism is involved in
      evaluations for precocious puberty, premature thelarche, and polycystic-ovary
      disease. Finally, the hypothalamo-pituitary-adrenal (HPA) axis is considered to
      be one of the major systems involved in fetal programming or in stress
      regulation. Most methods for the determination of steroid hormones are based on
      immunoassays, which are rapid and easy to perform. However, the reliability of
      several steroid immunoassays has been shown to be questionable because of the
      lack of specificity and of matrix effects. Immunological methods, especially
      direct assays, often overestimate true steroid values. Patient follow-up over
      time or between laboratories, as well as longitudinal studies, are therefore
      extremely difficult. This is of particular importance in pediatrics. Liquid
      chromatography triple quadrupole mass spectrometry (LC-MS/MS) is an increasingly
      common tool in the clinical laboratory and has the potential to overcome the
      limitations of immunoassays. LC-MS/MS affords the specificity, imprecision, and
      limits of quantification necessary for the reliable measurement of steroids,
      expanding diagnostic capabilities. In addition to the high throughput, the method
      requires minimal sample preparation and a small sample volume. All these features
      make it an attractive method to use in a clinical setting. Moreover, LC-MS/MS has
      the advantage that a spectrum of steroid hormones can be measured simultaneously.
      Steroid profiling is a very effective method for distinguishing almost all
      steroid-related disorders. It allows accurate diagnosis and is very useful in
      many clinical situations. Steroid profiles open up new vistas. The applicability
      for clinical samples and questions in pediatric endocrinology will be discussed.

PMID- 20036327
TI  - Insulin and hyperandrogenism in women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a very common endocrine disorder
      characterized by chronic anovulation, clinical and/or biochemical
      hyperandrogenism, and/or polycystic ovaries. But most experts consider that
      hyperandrogenism is the main characteristic of PCOS. Several theories propose
      different mechanisms to explain PCOS manifestations: (1) a primary enzymatic
      default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in
      gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH)
      secretion; or (3) alterations in insulin actions that lead to insulin resistance
      with compensatory hyperinsulinemia. However, in the past 20 years there has been
      growing evidence supporting that defects in insulin actions or in the insulin
      signalling pathways are central in the pathogenesis of the syndrome. Indeed, most
      women with PCOS are metabolically insulin resistant, in part due to genetic
      predisposition and in part secondary to obesity. But some women with typical PCOS
      do not display insulin resistance, which supports the hypothesis of a genetic
      predisposition specific to PCOS that would be revealed by the development of
      insulin resistance and compensatory hyperinsulinemia in most, but not all, women
      with PCOS. However, these hypotheses are not yet appropriately confirmed, and
      more research is still needed to unravel the true pathogenesis underlying this
      syndrome. The present review thus aims at discussing new concepts and findings
      regarding insulin actions in PCOS women and how it is related to
      hyperandrogenemia.

PMID- 20036332
TI  - Splenic autotransplantation restores IL-17 production and antibody response to
      Streptococcus pneumoniae in splenectomized mice.
AB  - The high incidence of overwhelming postsplenectomy infection caused by
      Streptococcus pneumoniae can be reduced by splenic autotransplantation. In this
      study the effect of splenectomy and splenic autotransplantation on the immune
      response to S. pneumoniae infection was investigated. Balb/c mice were divided
      into three groups: splenectomized (SP), splenectomized and autotransplanted (AT),
      and sham operated control (CT). Five days post-infection the serum antibody
      levels were measured and the number of S. pneumoniae CFU, neutrophil accumulation
      and IL-17 production in the liver and lungs were investigated. SP mice showed
      greater number of bacteria in both organs and lower serum levels of S. pneumoniae
      specific IgM, IgG1 and IgG2a antibodies. IL-17 production and neutrophil
      recruitment to the liver and lungs were lower in SP mice, in comparison with both
      the CT and the AT groups. Levels of S. pneumoniae-specific IgM, CFU counts,
      neutrophil accumulation and IL-17 production did not differ significantly between
      the CT and AT groups. These results suggest that splenic autotransplantation
      restores the capacity of splenectomized mice to fight S. pneumoniae infection.

PMID- 20036333
TI  - Pre-transplant soluble CD30 level as a predictor of not only acute rejection and
      graft loss but pneumonia in renal transplant recipients.
AB  - Pre-transplant sera of 586 renal graft recipients were tested to investigate
      whether soluble CD30 (sCD30) is a useful predictor of some severe clinical
      episodes post-transplant. Correlation analysis showed sCD30 level was
      significantly correlated with acute rejection (AR) (r=0.242, P<0.001), graft loss
      (r=0.162, P<0.001), and pneumonia (r=-0.147, P<0.001). Higher sCD30 levels were
      observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml,
      P<0.001). And patients with pneumonia had significantly lower pre-transplant
      sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based
      on statistical results, 120 and 240U/ml were selected as the optimal couple of
      cut-off value to divide patients into three groups: Group High (H), Group
      Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in
      Group L (P<0.001). Significant difference of AR rate was also observed between
      Group I (29.2%) and H (42.9%) (P<0.001). There were much more patients suffering
      pneumonia in Group L (P=0.001). Significantly lower 5-year patient survival rate
      (79.4%) was observed in Group H (P=0.016). These data showed that elevated pre
      transplant sCD30 level of renal allograft recipients may reflect an immune state
      detrimental for renal allograft survival. But sCD30 level lower than <120U/ml may
      be associated with a high risk of pneumonia. Pre-transplant sCD30 level is an
      independent predictor of acute rejection, lung infection, even graft survival.
      Suitable immunosuppression protocol should be selected according to pre
      transplant sCD30 level in an attempt to promote patient and graft survival.

PMID- 20036334
TI  - A validation framework for probabilistic maps using Heschl's gyrus as a model.
AB  - Probabilistic maps are useful in functional neuroimaging research for anatomical
      labeling and for data analysis. The degree to which a probability map can
      accurately estimate the location of a structure of interest in a new individual
      depends on many factors, including variability in the morphology of the structure
      of interest over subjects, the registration (normalization procedure and
      template) applied to align the brains among individuals for constructing a
      probability map, and the registration used to map a new subject's data set to the
      frame of the probabilistic map. Here, we take Heschl's gyrus (HG) as our
      structure of interest, and explore the impact of different registration methods
      on the accuracy with which a probabilistic map of HG can approximate HG in a new
      individual. We assess and compare the goodness of fit of probability maps
      generated using five different registration techniques, as well as evaluating the
      goodness of fit of a previously published probabilistic map of HG generated using
      affine registration (Penhune et al., 1996). The five registration techniques are:
      three groupwise registration techniques (implicit reference-based or IRG, DARTEL,
      and BSpline-based); a high-dimensional pairwise registration (HAMMER) as well as
      a segmentation-based registration (unified segmentation of SPM5). The accuracy of
      the resulting maps in labeling HG was assessed using evidence-based diagnostic
      measures within a leave-one-out cross-validation framework. Our results
      demonstrated the out performance of IRG and DARTEL compared to other registration
      techniques in terms of sensitivity, specificity and positive predictive value
      (PPV). All the techniques displayed relatively low sensitivity rates, despite
      high PPV, indicating that the generated probability maps provide accurate but
      conservative estimates of the location and extent of HG in new individuals.

PMID- 20036336
TI  - The effect of Neuregulin 1 on neural correlates of episodic memory encoding and
      retrieval.
AB  - Neuregulin 1 (NRG1) has been found to be associated with schizophrenia. Impaired
      performance in episodic memory tasks is an often replicated finding in this
      disorder. In functional neuroimaging studies, this dysfunction has been linked to
      signal changes in prefrontal and medial temporal areas. Therefore, it is of
      interest whether genes associated with the disorder, such as NRG1, modulate
      episodic memory performance and its neural correlates. Ninety-four healthy
      individuals performed an episodic memory encoding and a retrieval task while
      brain activation was measured with functional MRI. All subjects were genotyped
      for the single nucleotide polymorphism (SNP) rs35753505 in the NRG1 gene. The
      effect of genotype on brain activation was assessed with fMRI during the two
      tasks. While there were no differences in performance, brain activation in the
      cingulate gyrus (BA 24), the left middle frontal gyrus (BA 9), the bilateral
      fusiform gyrus and the left middle occipital gyrus (BA 19) was positively
      correlated with the number of risk alleles in NRG1 during encoding. During
      retrieval brain activation was positively correlated with the number of risk
      alleles in the left middle occipital gyrus (BA 19). NRG1 genotype does modulate
      brain activation during episodic memory processing in key areas for memory
      encoding and retrieval. The results suggest that subjects with risk alleles show
      hyperactivations in areas associated with elaborate encoding strategies.

PMID- 20036335
TI  - Computational and dynamic models in neuroimaging.
AB  - This article reviews the substantial impact computational neuroscience has had on
      neuroimaging over the past years. It builds on the distinction between models of
      the brain as a computational machine and computational models of neuronal
      dynamics per se; i.e., models of brain function and biophysics. Both sorts of
      model borrow heavily from computational neuroscience, and both have enriched the
      analysis of neuroimaging data and the type of questions we address. To illustrate
      the role of functional models in imaging neuroscience, we focus on optimal
      control and decision (game) theory; the models used here provide a mechanistic
      account of neuronal computations and the latent (mental) states represent by the
      brain. In terms of biophysical modelling, we focus on dynamic causal modelling,
      with a special emphasis on recent advances in neural-mass models for hemodynamic
      and electrophysiological time series. Each example emphasises the role of
      generative models, which embed our hypotheses or questions, and the importance of
      model comparison (i.e., hypothesis testing). We will refer to this theme, when
      trying to contextualise recent trends in relation to each other.

PMID- 20036337
TI  - Access to hematopoietic cell transplantation in the United States.
AB  - Hematopoietic cell transplantation (HCT) is a highly specialized and resource
      intense medical procedure that can be associated with disparities in access to
      transplantation. Barriers to access to HCT are multifactorial, complex, and
      interrelated. Our current knowledge of specific barriers that prevent access to
      HCT is very limited. As the utilization of HCT increases, it is imperative that
      underserved populations receive the benefit of this life-saving procedure. We
      review the prevailing literature on access to HCT and describe research
      priorities for eliminating disparities in transplantation. Better understanding
      of these complex barriers will minimize inequities, inform health policy, guide
      development of interventions targeted to eliminate disparities, and continue the
      expansion of HCT in the future.

PMID- 20036338
TI  - Uncinate processes in birds: morphology, physiology and function.
AB  - The avian respiratory system is remarkable in terms of its complexity and
      efficiency. The evolution of this system with its unique lung morphology and
      physiology has contributed to birds being one of the most successful vertebrate
      lineages. Despite holding the attention of the scientific community for a long
      time, much remains to be discovered about the complexities of this system. Recent
      advances have highlighted the important role that accessory breathing structures,
      the uncinate processes, play in understanding not only how this system functions
      but how it evolved. Almost all species of extant bird have uncinate processes
      extending from the midpoint of the vertebral ribs. These processes are integral
      to the mechanics of ventilation in birds, being active in both inspiration and
      expiration but also playing some role during locomotion. The morphological
      variation in the uncinate processes suggests that the constraints placed on the
      body by adaptations to different forms of locomotion are key to understanding
      differences in how birds breathe. These processes also occur in the theropod
      dinosaurs, providing further evidence that they are the ancestors of modern birds
      but also highlighting the intrinsic flexibility in the ventilatory systems of
      these animals.

PMID- 20036339
TI  - High-calcium diet reduces blood pressure, blood volume and preserves
      vasorelaxation in oral contraceptive-treated female rats.
AB  - Cardiovascular complications are the major clinical challenges among users of
      synthetic steroids in oral contraceptive (OC) formulations. Interventions that
      reduce blood volume and improve vasorelaxation have been shown to reduce
      hypertension and the associated risk factors. The aim of the present study was to
      investigate the influence of increasing dietary calcium from 0.9 to 3.0% on the
      development of OC-induced high blood pressure and associated changes in female
      Sprague-Dawley rats treated with a combination of OC steroids (1 microg ethinyl
      estradiol and 10 microg norgestrel; p.o.) daily for 10 weeks. Results showed that
      OC administration led to significant increases in blood pressure, blood volume
      and cardiac weight. Conversely, OC caused significant reductions in body weight,
      urinary excretion of water, plasma levels of calcium, 17beta-estradiol and
      progesterone. Increased dietary calcium attenuated the elevation in blood
      pressure induced by OC and abrogated the associated changes in blood volume,
      cardiac weight, plasma calcium and urinary excretion of water. The endothelium
      dependent relaxation responses to acetylcholine and endothelium-independent
      relaxation responses to sodium nitroprusside in noradrenaline-precontracted
      aortic rings were not significantly different among the groups. The results
      indicate that increased calcium intake abrogated the development of high blood
      pressure and associated increased blood volume and cardiac weight during OC
      treatment. The beneficial effect of increased dietary calcium during OC use may
      be explained by improved diuretic and preserved vasorelaxant responses.

PMID- 20036340
TI  - Esophageal intramural pseudodiverticulosis: a rare cause of esophageal stricture.

PMID- 20036341
TI  - Gastrojejunocolic fistula overlooked as an ulcer in endoscopy.

PMID- 20036342
TI  - Tetrandrine attenuates lipopolysaccharide-induced fulminant hepatic failure in D
      galactosamine-sensitized mice.
AB  - Fulminant hepatic failure (FHF) remains an extremely poor prognosis and high
      mortality; better treatments are urgently needed. Tetrandrine (TET), a
      traditional anti-inflammatory drug, has been reported to exhibit hepatoprotective
      activities in several liver injury models. We now investigated the effects and
      underlying mechanisms of TET on lipopolysaccharide (LPS) and D-galactosamine (D
      GalN)-induced FHF in mice. TET (50, 100, and 200 mg/kg) was given
      intraperitoneally 1h before LPS/D-GalN injection in mice. The mortality and liver
      injury was evaluated subsequently. The results showed that administering TET to
      mice reduced mortality and improved liver injury induced by LPS/D-GalN in a dose
      dependent manner. In addition, TET dose-dependently inhibited LPS/D-GalN-induced
      NF-kappaB activation, serum and hepatic tissues tumor necrosis factor-alpha (TNF
      alpha) production, caspase-3 activation and hepatocellular apoptosis,
      myeloperoxidase (MPO) activity, intercellular adhesion molecule-1 (ICAM-1) and
      endothelial cell adhesion molecule-1 (ECAM-1) expression. Our experimental data
      indicated that TET might alleviate the FHF induced by LPS/D-GalN through
      inhibiting NF-kappaB activation to reduce TNF-alpha production.

PMID- 20036343
TI  - The geoepidemiology of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with manifold
      clinical manifestations and immunological abnormalities, affecting primarily
      women. Although accurate current data on its incidence and prevalence are largely
      lacking, there are numerous indications that SLE is far less common in Europeans
      and their descendants compared to all other ethnicities. The clinical
      manifestations of the disease show geographic or ethnic variation, generally
      being less severe in patients of European ancestry than in African, Asian,
      certain "Hispanic" or mestizo, and various indigenous populations. In particular,
      renal involvement is far more common in non-European patients. Genetic as well as
      environmental, sociodemographic and sociocultural factors are likely to
      contribute to the differences in the incidence and clinical expression of SLE.

PMID- 20036344
TI  - Cortical sources of the respiratory-related evoked potential.
AB  - The respiratory-related evoked potential (RREP) is increasingly used to study the
      neural processing of respiratory signals. However, little is known about the
      cortical origins of early (Nf, P1, N1) and later RREP components (P2, P3). By
      using high-density EEG, we studied cortical sources of RREP components elicited
      by short inspiratory occlusions in 18 healthy volunteers (6 female, mean age
      20.0+/-1.8 years). Topographical maps for Nf and P1 showed bilateral maximum EEG
      voltages over the frontal and centro-parietal cortex, respectively. Cortical
      source analyses (minimum-norm estimates) in addition to topographical maps
      demonstrated bilateral sensorimotor cortex origins for N1 and P2 which were
      paralleled by an additional frontal cortex source (p's<0.05). The source of the
      P3 was located at the parietal cortex (p<0.05). The results support previous
      findings on the cortical sources of early RREP components Nf, P1 and N1 and
      demonstrate the cortical sources of later RREP components P2 and P3.

PMID- 20036345
TI  - bFGF-Modified BMMSCs enhance bone regeneration following distraction osteogenesis
      in rabbits.
AB  - Distraction osteogenesis (DO), which induces new bone formation along the vector
      of pull without requiring the use of bone graft, has become a valuable surgical
      method for patients with limb discrepancy or craniofacial microsomia. However,
      the long treatment period and possible fibrous union or nonunion hampers its
      further clinical application. Bone marrow mesenchymal stem cells (BMMSCs) have
      been widely used as a source of cell therapy or a vector for gene transfer. Basic
      fibroblast growth factor (bFGF) has high potential for promotion of bone
      regeneration. However, bFGF has a short half value period in vivo. In this study,
      osteodistraction was applied in craniofacial bone of rabbit to observe the
      effects of BMMSCs with or without bFGF gene transfected on bone regeneration in
      the distracted zone. Mandibular lengthening (10 mm) was performed in 42 New
      Zealand white rabbits using a rapid distraction rate (2 mm/day). The animals were
      then randomly divided into group A, group B and group C (n=14 for each group). At
      the end of distraction, physiological saline, autologous BMMSCs and BMMSCs
      transfected with bFGF were injected into the distraction gaps in groups A, B, and
      C, respectively. Eight weeks after DO, the rabbits were sacrificed, and the
      distracted mandibles were harvested and processed for radiography, dual energy x
      ray absorptiometry (DXA), micro-CT, histology and three-point bend testing. Under
      a rapid distraction, immature or poor bone healing was observed in the distracted
      callus from group A. However, better bone formation and higher bone mineral
      density (BMD) and bone mineral content (BMC) in the distracted callus were
      observed in group B and group C, the latter showed excellent bone formation and
      highest BMD and BMC. Such finding was confirmed by histological and micro-CT
      examinations. The values of BT/TV in group C were highest and the micro
      architecture presented more mature characteristics. The mechanical strength in
      group C was 1.63-fold and 1.28-fold greater than that in group A and B by three
      point bending testing. The results of this study suggest that BMMSCs
      transplantation can promote bone formation in DO, and bFGF-modified BMMSCs were
      more effective in this enhancement.

PMID- 20036346
TI  - Osteocalcin immunolabeling during the alveolar healing process in ovariectomized
      rats treated with estrogen or raloxifene.
AB  - The influence of an estrogen-deficient state was evaluated in this study and also
      its treatments with estrogen (E(2)) or with raloxifene (RLX) on the expression of
      osteocalcin during the periods of the chronology of the alveolar bone healing
      process (7, 14, 21, 28 and 42 post-extraction days) by means of
      immunohistochemistry reactions and histomorphometric analysis. Rats (200-220 g)
      with oestrus cycles normal were either OVX or sham-operated and divided into four
      groups: sham, OVX control (OVX/O), estrogen (OVX/E(2); 17 beta-estradiol, 400
      microg/mo) and raloxifene (OVX/RLX; 1 mg/kg bw/d) groups. Histomorphometric
      analysis showed the sham group presented the highest mean value of bone formation
      post-extraction. The reaction of immunohistochemistry for osteocalcin presented
      stronger expression of osteocalcin with predominance at 14 and 21 days on sham
      group. The OVX/RLX group presented better results than OVX/E(2), considering the
      expression of osteocalcin in osteoblastic lineage cells, but still inferior than
      the sham group. It was concluded that ovariectomy decreases the mineralization
      process and the osteocalcin expression during the chronology of the alveolar
      healing process that is not totally recovered with estrogen replacement or
      raloxifene treatment.

PMID- 20036347
TI  - ADAMTS-5 deficient mice do not develop mechanical allodynia associated with
      osteoarthritis following medial meniscal destabilization.
AB  - OBJECTIVE: To characterize pain-related behavior during the course of knee
      osteoarthritis (OA) induced by destabilization of the medial meniscus (DMM) in
      wild type (WT) and in ADAMTS-5 null mice. METHODS: DMM surgery was performed in
      the right knee of CD-1 mice. At regular intervals up to 8 weeks after surgery,
      mice were assessed for the following parameters: mechanical allodynia (via
      withdrawal thresholds to von Frey filaments applied to the plantar surface of
      both hind paws or to the tail), thermal hyperalgesia, locomotor activity and gait
      analysis. In addition, mechanical allodynia was tested in C57BL/6 WT or ADAMTS-5
      null mice following DMM surgery. RESULTS: In CD-1 mice, a robust and progressive
      decrease in withdrawal threshold was observed in both hind paws after DMM but not
      sham surgery. Allodynia was apparent as early as 14 days postoperatively. Both
      sexes developed OA changes after surgery with concurrent mechanical allodynia. No
      other pain-related behavioral changes were detected up to 8 weeks post-surgery.
      In C57BL/6 mice, a genetic background in which only males develop OA changes
      after DMM, males but not females developed allodynia in the ipsilateral hind paw.
      In contrast, C57BL/6 ADAMTS-5 null mice did not develop OA changes or mechanical
      allodynia up to 8 weeks post-surgery. CONCLUSION: Joint pathology following DMM
      surgery in mice is associated with progressive mechanical allodynia. ADAMTS-5
      null mice are resistant to DMM-induced OA-like lesions and to the associated
      mechanical allodynia.

PMID- 20036348
TI  - Categorization and action: what about object consistence?
AB  - Categorization studies have focused on the importance of a variety of perceptual
      properties (shape, size, weight). The present study explored whether the softness
      or hardness of an object might influence the way we categorize and consider
      category members. Of additional interest was whether information on consistence
      is automatically activated and whether it is modulated by the kind of task and of
      response modality. Three experiments demonstrated that information on consistence
      is automatically activated, and it helps us to distinguish between artefacts and
      natural objects. Interestingly, the results are in agreement with the simulation
      hypothesis; namely, when we consider artefacts, we simulate using them and
      information on their consistence is activated; this simulation is modulated by
      the task. The way we differently process artefacts and natural objects across the
      experiments confirms the simulation hypothesis and our sensitivity to the
      response modality.

PMID- 20036350
TI  - Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216
      mutation.
AB  - Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease
      manifested by psychomotor retardation, hypotonia, ataxia, nystagmus, and
      oculomotor apraxia and variably associated with dysmorphism, as well as retinal
      and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and
      additional anomalies of the fourth ventricle, corpus callosum, and occipital
      cortex. The disease has previously been mapped to the centromeric region of
      chromosome 11. Using homozygosity mapping in 13 patients from eight Ashkenazi
      Jewish families, we identified a homozygous mutation, R12L, in the TMEM216 gene,
      in all affected individuals. Thirty individuals heterozygous for the mutation
      were detected among 2766 anonymous Ashkenazi Jews, indicating a carrier rate of
      1:92. Given the small size of the TMEM216 gene relative to other JBTS genes, its
      sequence analysis is warranted in all JBTS patients, especially those who suffer
      from associated anomalies.

PMID- 20036349
TI  - Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy and interact
      with FCD4 on chromosome 9p.
AB  - Fuchs corneal dystrophy (FCD) is a degenerative genetic disorder of the corneal
      endothelium that represents one of the most common causes of corneal
      transplantation in the United States. Despite its high prevalence (4% over the
      age of 40), the underlying genetic basis of FCD is largely unknown. Here we
      report missense mutations in TCF8, a transcription factor whose
      haploinsufficiency causes posterior polymorphous corneal dystrophy (PPCD), in a
      cohort of late-onset FCD patients. In contrast to PPCD-causing mutations, all of
      which are null, FCD-associated mutations encode rare missense changes suggested
      to cause loss of function by an in vivo complementation assay. Importantly,
      segregation of a recurring p.Q840P mutation in a large, multigenerational FCD
      pedigree showed this allele to be sufficient but not necessary for pathogenesis.
      Execution of a genome-wide scan conditioned for the presence of the 840P allele
      identified an additional late-onset FCD locus on chromosome 9p, whereas haplotype
      analysis indicated that the presence of the TCF8 allele and the disease haplotype
      on 9p leads to a severe FCD manifestation with poor prognosis. Our data suggest
      that PPCD and FCD are allelic variants of the same disease continuum and that
      genetic interaction between genes that cause corneal dystrophies can modulate the
      expressivity of the phenotype.

PMID- 20036352
TI  - [RETRAIT: Descriptive epidemiology of thyroid cancer in France: Incidence,
      mortality and survival.]

PMID- 20036351
TI  - Descriptive epidemiology of thyroid cancer in France: incidence, mortality and
      survival.
AB  - OBJECTIVES: Describe time trends of incidence and mortality associated with
      thyroid cancer and provide 1 and 5-year survivals by histological group in French
      areas covered by cancer registries. MATERIAL AND METHODS: Data for 1975 to 2004
      were provided by one thyroid-dedicated and 11 general registries. Incidence
      estimates were obtained by correction of incidence from areas with registries,
      then projections for 2008 were derived. Overall and relative survivals by sex and
      age (diagnosis period 1989-1997; cut-off date 1st January 2002) were obtained
      from the dedicated and nine other registries. Comparisons between areas or time
      periods used world-standardized rates. RESULTS: Between 1980 and 2005, incidence
      increased but mortality decreased in men and women. Annual cases increased five
      times and projections for 2008 were 8,000 cases and 400 deaths. The main
      increasing subtype was papillary carcinoma. One-year overall and relative
      survivals were 92 and 94%, respectively. Five-year overall and relative survivals
      were 87 and 93%, respectively. The highest survival (>94%) concerned papillary
      carcinomas and the lowest (<15%) anaplastic carcinomas. Survivals were generally
      higher in women than in men; precisely, higher in women for papillary and
      follicular carcinomas but higher in men for medullary and anaplastic carcinomas.
      Survivals increased with age, but for medullary carcinomas. Survivals from
      anaplastic carcinomas were very low whatever the age. CONCLUSION: The increase of
      thyroid cancer frequency is dramatic but survivals are improving. Though the
      prognosis of the most increasing histological subtype is generally good, it
      remains very important to identify the causes of this steady increase to
      implement adequate preventive measures.

PMID- 20036353
TI  - Self-discrepancy in students with bipolar disorder II or NOS.
AB  - BACKGROUND: Studies on self-representation in bipolar disorder have mainly
      focused on the single dimension of self-esteem and recruited patients either in
      episode or in remission. The aim of the study was to examine multi-dimensional
      aspects of the self (discrepancy between actual- and ideal-selves and between
      actual- and feared-selves) in a student sample with a history of significant
      experience of hypomania (with or without experience of major depression) as
      compared to healthy control students. METHODS: Bipolar students and healthy
      control students completed the Self-Discrepancy Questionnaire (SDQ: Carver,
      Lawrence, & Scheier, 1999). The degree of similarity to, and the perceived
      likelihood of ideal-self and feared-self characteristics were assessed. RESULTS:
      The difference between the groups in level of ideal-self similarity was at trend
      level. Students with prior hypomania but no history of depression showed higher
      similarity to their feared-self than healthy controls and also rated themselves
      as more likely to have these feared-self characteristics in the future.
      LIMITATION: The small sample size, especially in the bipolar group with no
      history of depression, limits the power of the study. CONCLUSIONS: The presence
      of ideal-self discrepancy was not convincingly demonstrated in this sample and it
      is possible that where it has been identified in previous studies it may, at
      least in part, represent a scar of previous episodes of depression or mania
      rather than a predisposing factor. However a sub-sample of students who had
      experienced hypomania in the absence of history of depression were distinguished
      from healthy controls in perceived closeness to the feared-self qualities. The
      feared-self concept warrants further investigation in bipolar patients.

PMID- 20036354
TI  - Cyclophosphamide induces bone marrow to yield higher numbers of precursor
      dendritic cells in vitro capable of functional antigen presentation to T cells in
      vivo.
AB  - We have shown recently that cyclophosphamide (CTX) treatment induced a marked
      increase in the numbers of immature dendritic cells (DCs) in blood, coinciding
      with enhanced antigen-specific responses of the adoptively transferred CD8(+) T
      cells. Because this DC expansion was preceded by DC proliferation in bone marrow
      (BM), we tested whether BM post CTX treatment can generate higher numbers of
      functional DCs. BM was harvested three days after treatment of C57BL/6 mice with
      PBS or CTX and cultured with GM-CSF/IL-4 in vitro. Compared with control, BM from
      CTX-treated mice showed faster generation and yielded higher numbers of DCs with
      superior activation in response to toll-like receptor (TLR) agonists. Vaccination
      with peptide-pulsed DCs generated from BM from CTX-treated mice induced
      comparable adjuvant effects to those induced by control DCs. Taken together, post
      CTX BM harbors higher numbers of DC precursors capable of differentiating into
      functional DCs, which be targeted to create host microenvironment riches in
      activated DCs upon treatment with TLR agonists.

PMID- 20036355
TI  - B1 cells produce nitric oxide in response to a series of toll-like receptor
      ligands.
AB  - The effect of a series of toll-like receptor (TLR) ligands on the production of
      nitric oxide (NO) in mouse B1 cells was examined by using CD5(+) IgM(+) WEHI 231
      cells. The stimulation with a series of TLR ligands, which were Pam3Csk4 for
      TLR1/2, poly I:C for TLR3, lipopolysaccharide (LPS) for TLR4, imiquimod for TLR7
      and CpG DNA for TLR9, resulted in enhanced NO production via augmented expression
      of an inducible type of NO synthase (iNOS). LPS was most potent for the
      enhancement of NO production, followed by poly I:C and Pam3Csk4. Imiquimod and
      CpG DNA led to slight NO production. The LPS-induced NO production was dependent
      on MyD88-dependent pathway consisting of nuclear factor (NF)-kappaB and a series
      of mitogen-activated protein kinases (MAPKs). Further, it was also dependent on
      the MyD88-independent pathway consisting of toll-IL-1R domain-containing adaptor
      inducing IFN-beta (TRIF) and interferon regulatory factor (IRF)-3. Physiologic
      peritoneal B1 cells also produced NO via the iNOS expression in response to LPS.
      The immunological significance of TLR ligands-induced NO production in B1 cells
      is discussed.

PMID- 20036356
TI  - Beethoven's last piano sonata and those who follow crocodiles: cross-domain
      mappings of auditory pitch in a musical context.
AB  - Though auditory pitch is customarily mapped in Western cultures onto spatial
      verticality (high-low), both anthropological reports and cognitive studies
      suggest that pitch may be mapped onto a wide variety of other domains. We
      collected a total number of 35 pitch mappings and investigated in four
      experiments how these mappings are used and structured. In particular, we
      inquired (1) how Western subjects apply Western and non-Western metaphors to
      "high" and "low" pitches, (2) whether mappings applied in an abstract conceptual
      task are similarly applied by listeners to actual music, (3) how mappings of
      spatial height relate to these pitch mappings, and (4) how mappings of "high" and
      "low" pitch associate with other dimensions, in particular quantity, size,
      intensity and valence. The results show strong agreement among Western
      participants in applying familiar and unfamiliar metaphors for pitch, in both an
      abstract, conceptual task (Exp. 1) and in a music listening task (Exp. 2),
      indicating that diverse cross-domain mappings for pitch exist latently besides
      the common verticality metaphor. Furthermore, limited overlap between mappings of
      spatial height and pitch height was found, suggesting that, the ubiquity of the
      verticality metaphor in Western usage notwithstanding, cross-domain pitch
      mappings are largely independent of that metaphor, and seem to be based upon
      other underlying dimensions. Part of the discrepancy between spatial height and
      pitch height is that, for pitch, "up" is not necessarily "more," nor is it
      necessarily "good." High pitch is only "more" for height, intensity and
      brightness. It is "less" for mass, size and quantity. We discuss implications of
      these findings for music and speech prosody, and their relevance to notions of
      embodied cognition and of cross-domain magnitude representation.

PMID- 20036358
TI  - High prevalence of endometriosis in infertile women with normal ovulation and
      normospermic partners.

PMID- 20036359
TI  - Surgery in advanced borderline tumors.
AB  - Our retrospective study evaluates the role of conservative surgery, performed in
      10 of 22 patients affected by advanced stage serous borderline ovarian tumor.
      Although patients who underwent conservative surgery had a higher recurrence rate
      (60% after conservative surgery and 8% after radical surgery), all patients are
      alive without evidence of disease.

PMID- 20036360
TI  - The experiences of health care workers employed in an Australian intensive care
      unit during the H1N1 Influenza pandemic of 2009: a phenomenological study.
AB  - BACKGROUND: The H1N1 Influenza A pandemic arrived in Australia in early May 2009.
      In Queensland, the highest number of H1N1 cases were admitted to the intensive
      care unit when compared with the other Australian states. While many recent
      studies examining the H1N1 pandemic have focussed on service delivery and disease
      epidemiology, few have explored the lived experiences of frontline health care
      workers caring for the patients in the intensive care unit. OBJECTIVES: The
      purposes of this study were to: document and describe the lived experiences of
      the nursing and medical staff caring for patients in the intensive care unit
      during the H1N1 pandemic; to validate the staffs' experiences; and to assist in
      informing future pandemic planning by highlighting the collective experiences of
      these frontline health care workers. DESIGN: A phenomenological study method was
      used. SETTING AND PARTICIPANTS: 34 staff from a tertiary referral hospital in
      Brisbane, Australia participated in the study. METHODS: Data was collected using
      an open ended questionnaire and focus groups. The resulting responses were
      analysed using Colaizzi's framework to discover regular patterns of meaning that
      emerged. RESULTS: Eight common themes emerged: the wearing of personal protective
      equipment; infection control procedures; the fear of contracting and transmitting
      the disease; adequate staffing levels within the intensive care unit; new roles
      for staff; morale levels; education regarding extracorporeal membrane
      oxygenation; and the challenges of patient care. These eight themes articulate
      the lived experience of the staff during the height of the H1N1 Influenza
      pandemic period. CONCLUSIONS: Planning for a pandemic situation is invariably
      difficult due to the unpredictable nature of the event itself. Recommendations
      for future pandemic planning which can be drawn from this study include the
      appointment of a dedicated infection control representative to provide
      information and support regarding infection control matters; the maintenance of
      effective communication channels is crucial; and the increased staffing
      requirements across nursing, medical, allied health and ancillary staff to cope
      with the higher patient numbers and acuity must be anticipated and planned for.

PMID- 20036361
TI  - Evaluation of the effects of a birth plan on Taiwanese women's childbirth
      experiences, control and expectations fulfilment: a randomised controlled trial.
AB  - BACKGROUND: In many western countries, pregnant women often prepare birth plans,
      outlining how they would like their childbirth experiences to proceed. However
      there have been no experimental studies to evaluate the effect of birth plans.
      OBJECTIVE: The objective of this research was to evaluate the effects of birth
      plans on women's fulfilment of their childbirth expectations, their control over
      the birth process, and overall experiences. DESIGN: A randomised, single-blind
      controlled trial study design was used. SETTINGS: This study involved seven
      hospitals and 10 obstetricians in Taiwan. PARTICIPANTS: Participants included
      primiparous women, each under the care of one of seven Taiwanese medical
      facilities, and who had been pregnant for at least 32 weeks. They were also at
      least 18 years old, and had no pregnancy complications. An exclusion criterion
      was elective caesarean as a mode of delivery. A total of 296 women in hospital
      clinics who met the study criteria were allocated by block randomisation to
      experimental (n=155) or control (n=141) groups. METHODS: The women completed
      their basic personal information and a childbirth expectations questionnaire when
      they were recruited. One day after delivery, all the participants completed a
      questionnaire about the childbirth experience, control and fulfilment of their
      childbirth expectations. RESULTS: The experimental group had a statistically
      higher degree of positive childbirth experiences than that of the control group
      (t=2.48, p=0.01). The experimental group also showed a higher degree of
      childbirth control (t=9.60, p<0.001). There were no noticeable differences in
      mean values between the experimental and control groups in prenatal birth
      expectations, but a significant difference (t=2.63, p=0.01) in the degree of
      fulfilment of their childbirth expectations after delivery. On a subscale
      measuring the fulfilment of childbirth expectations, there was a statistically
      higher degree of mastery and participation (t=3.74, p<0.001) in the experimental
      group than in the control group. CONCLUSIONS: The results justify the clinical
      implementation of birth plans. Providing birth plans in medical facilities is an
      effective means of fulfilling pregnant women's childbirth expectations, of
      affording them a larger degree of control over the birth process, and for their
      overall positive experiences. Birth plans are acceptable and feasible in
      maternity care.

PMID- 20036362
TI  - The effectiveness of a multidisciplinary pain management programme managing
      chronic pain on pain perceptions, health-related quality of life and stages of
      change--A non-randomized controlled study.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) has been useful in the treatment
      of chronic pain conditions for many years. Given the increasing number of persons
      with chronic pain and associated psychosocial problems, the development and
      implementation of effective interventions based on CBT is warranted. OBJECTIVES:
      The aim of this study is to evaluate the effects of a multidisciplinary pain
      management programme on health-related quality of life (HRQL), as measured by the
      Short Form Health Survey (SF-36), pain perception as measured by the Brief Pain
      Inventory (BPI), and readiness-to-change as measured by the Pain Stages of Change
      Questionnaire (PSOCQ). DESIGN: A pretest-post-test quasi-experimental design,
      with waiting list controls and baseline and post-test measures, was used.
      SETTING: The study was conducted in the rehabilitation unit of a university
      hospital. PARTICIPANTS: Of 117 people suffering from chronic pain, 113 completed
      the 8-week multidisciplinary pain management programme. The patients were
      consecutive referrals. Inclusion criteria were: adults (18-67 years), pain
      lasting over 6 months, motivation and no ongoing litigation. Exclusion criteria
      were affected by major mental disorders or major medical conditions requiring
      treatment. METHODS: The intervention was based on a cognitive behavioural
      approach. Therapeutic dialogues and training, combined with physical activity,
      were provided to a fixed plan, including homework. The programme has several
      features that directly address psychosocial aspects of chronic pain. Statistical
      and clinical significance are considered. RESULTS: The findings suggest that this
      programme has the potential to improve HRQL, reduce pain intensity and
      interference, and contribute to improvement in readiness-to-change. Statistically
      significant results are supplemented by results showing their clinical
      significance. CONCLUSIONS: Improvements in HRQL, pain-related disability, and
      readiness-to-change suggest that the vicious cycle of chronic pain may be
      alleviated by our programme. As we see it, effective treatment results are about
      identifying and addressing the important and changeable influences maintaining
      pain problems such as acceptance, understanding the mind-body connection and self
      management. Although further research is needed to evaluate the effectiveness of
      this work, such group approaches appear to represent a feasible treatment option
      for many patients with chronic pain.

PMID- 20036363
TI  - Early intensive statin treatment for six months improves long-term clinical
      outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a
      follow-up study.
AB  - BACKGROUND: The ESTABLISH trial found using volumetric intravascular ultrasound
      that atorvastatin therapy started early and continued for 6 months significantly
      reduced plaque volume in patients with acute coronary syndrome (ACS). However,
      the benefits of early statin administration on long-term outcomes remain unclear.
      We therefore examined whether the early initiation of statin in patients with ACS
      improves long-term prognosis. METHODS AND RESULTS: The Extended-ESTABLISH trial
      included 180 patients with ACS who underwent emergency percutaneous coronary
      intervention (PCI). These patients were randomized here to groups given either
      early intensive lipid-lowering therapy (n=90; atorvastatin 20 mg/day) or standard
      care (control, n=90) within 48 h of events. Baseline characteristics between the
      two groups did not significantly differ at the time of ACS onset. Six months
      after PCI, all patients were treated with statins to achieve an LDL-C value of
      <100 mg/dL. We compared the first occurrence of major adverse cardiac and
      cerebrovascular events (MACCE). Prognostic data were fully documented during the
      entire follow-up period (mean, 1538+/-707 days). Cumulative event-free survival
      was significantly higher in the atorvastatin, than in the control group (p=0.041;
      log-rank test). Furthermore, by adjusting for validated prognosticators, early
      statin administration was identified as a good predictor of MACCE (HR 0.46, 95%CI
      0.23-0.86; p=0.015). CONCLUSIONS: In-hospital initiation of statin therapy
      immediately after ACS conferred long-term benefits and 6 months of intensive
      lipid-lowering therapy improved long-term clinical outcomes after PCI in patients
      with ACS.

PMID- 20036364
TI  - What is the clinical relevance of the prothrombin G20210A mutation?

PMID- 20036365
TI  - Association of genetic variants in SEMA3F, CLEC16A, LAMA3, and PCSK2 with
      myocardial infarction in Japanese individuals.
AB  - OBJECTIVE: The purpose of the present study was to identify genetic variants that
      confer susceptibility to myocardial infarction (MI) in Japanese individuals.
      METHODS: The study population comprised 5014 Japanese individuals, including 1444
      subjects with MI and 3570 controls. The 150 polymorphisms examined in the present
      study were selected by a genome-wide association study for ischemic stroke with
      the use of the GeneChip Human Mapping 500K Array Set (Affymetrix), and were
      determined by a method that combines the polymerase chain reaction and sequence
      specific oligonucleotide probes with suspension array technology. RESULTS: An
      initial screen by the chi-square test revealed that the A-->G polymorphism of
      SEMA3F (rs12632110), the C-->T polymorphism of CLEC16A (rs9925481), the A-->G
      polymorphism of LAMA3 (rs12373237), and the C-->G polymorphism of PCSK2
      (rs6080699) were significantly (false discovery rate for allele frequencies of
      <0.05) associated with MI. Subsequent multivariable logistic regression analysis
      with adjustment for covariates and a stepwise forward selection procedure
      revealed that the A-->G polymorphism of SEMA3F (dominant model; P=0.0014; odds
      ratio, 0.76), the C-->T polymorphism of CLEC16A (dominant model; P=0.0009; odds
      ratio, 0.75), the A-->G polymorphism of LAMA3 (recessive model; P=0.0099; odds
      ratio, 0.80), and the C-->G polymorphism of PCSK2 (recessive model; P=0.0155;
      odds ratio, 1.19) were significantly (P<0.05) associated with the prevalence of
      MI. CONCLUSION: Determination of these genotypes may prove informative for
      assessment of the genetic risk for MI in Japanese individuals.

PMID- 20036366
TI  - A technique for the quantification of the 3D connectivity of thin articulations
      in bony sutures.
AB  - The anatomy and development of cranial and facial sutures have been studied in
      detail using histological sections, 2D radiographs and more recently CT imaging.
      However, little attention has been paid to evaluating and quantifying the
      connectivity of these thin cortical bone articulations. More recent technological
      advances such as micro-CT imaging has the potential to be used to provide
      quantitative measurements of 3D connectivity in bony articulations. This study
      presents a new technique for quantifying the connectivity of bony projections
      inside cranial and facial sutures using a combination of skeletonization,
      thinning algorithms and 3D intensity mapping. The technique is demonstrated in
      five sutures through semi-automated analysis and image processing of microCT
      scans. In the sagittal, coronal and frontozygomatic sutures an average bone
      connectivity of 6.6-11.6% was found with multiple bony projections providing an
      interlocking structure between adjacent bones. Much higher bone connectivity was
      present in the zygomaticotemporal and zygomaticomaxillary sutures (22.7-37.4%)
      with few bony projections. This method combining microCT scanning and image
      processing techniques was successfully used to quantify the connectivity of thin
      bone articulations and allowed detailed assessment of sutural fusion in 3D. The
      wider application of this technique may allow quantification of connectivity in
      other structures, in particular fracture healing of long bones.

PMID- 20036367
TI  - Solid phase extraction of copper(II) by fixed bed procedure on cation exchange
      complexing resins.
AB  - The efficiency of the metal ion recovery by solid phase extraction (SPE) in
      complexing resins columns is predicted by a simple model based on two parameters
      reflecting the sorption equilibria and kinetics of the metal ion on the
      considered resin. The parameter related to the adsorption equilibria was
      evaluated by the Gibbs-Donnan model, and that related to the kinetics by assuming
      that the ion exchange is the adsorption rate determining step. The predicted
      parameters make it possible to evaluate the breakthrough volume of the considered
      metal ion, Cu(II), from different kinds of complexing resins, and at different
      conditions, such as acidity and ionic composition.

PMID- 20036368
TI  - Adhesion force between cyclopentane hydrates and solid surface materials.
AB  - The mechanisms by which hydrates deposit in a petroleum production line are
      related to pipeline surface properties, fluid composition and properties, and
      water cut. In this work, adhesion forces between cyclopentane hydrates and solid
      surfaces were investigated as a function of the solid material, the presence of
      water and the presence of petroleum acids in the oil phase. The influence of
      dissolved water on hydrate adhesion forces was also investigated. The results
      show that the adhesion force between hydrates and solid surfaces was dependent on
      the surface material; solids with low surface free energy lead to the lowest
      adhesion forces. The adhesion force was strongly dependent on the presence of
      water in the system. When a water drop was deposited on the solid surface, the
      adhesion force between the hydrate and the solid surface was more than 10 times
      larger than hydrate-hydrate adhesion forces. The presence of a water-saturated
      oil phase also led to an increase in adhesion force between hydrate particles.
      Adhesion forces were highest when the solid surfaces are water-wet. Addition of
      petroleum acids to the oil phase drastically reduced adhesion forces.

PMID- 20036369
TI  - Wettability of quartz in presence of nonionic surfactants and short chain
      alcohols mixtures.
AB  - Measurements of advancing contact angles for aqueous solution of Triton X-100 (TX
      100) with methanol, ethanol and propanol mixtures and Triton X-165 (TX-165) with
      the same alcohols on quartz surface were carried out. From the obtained results
      it appeared that the wettability of quartz depends on Triton's and alcohol
      concentrations and that there is a linear dependence between the adhesional and
      surface tension of aqueous solution of Triton's and alcohols mixtures. This
      dependence can be described by linear equations which constants depend somewhat
      on the Triton's and alchohols concentration. The slope of all linear dependencies
      between the adhesional and surface tension is positive. The critical surface
      tension of quartz wetting determined from these dependencies by extrapolating the
      adhesional tension to a value equal to the surface tension (for contact angle
      equal zero) depends on the assumption whether the concentration of Triton or
      alcohols was constant. The average value at constant Triton's concentration was
      equal to 27.1 mN/m and was lower than that evaluated at constant alcohol
      concentration (29.5 mN/m). The critical surface tension of quartz wetting at
      constant alcohol concentration was nearly the same as the apolar component of the
      surface tension of quartz covered with water monolayer film. The positive slope
      of the adhesional-surface tension curves and the work of water adhesion, Triton's
      and alcohols to quartz surface indicates that the interaction between water
      molecules and quartz surface might be stronger than that between quartz and
      surface active agents molecules. So, the concentration excess of surfactants at
      quartz-water interface is probably negative, and the possibility of the surface
      active agents to adsorb at quartz/water film-water interface is higher than that
      at the quartz-water. However, at alcohol concentration above that of its
      aggregation the molecules of the surface active agents probably destroy the
      strongly ordered film of water.

PMID- 20036370
TI  - Adsorption of Basic Violet 14 in aqueous solutions using KMnO4-modified activated
      carbon.
AB  - In this paper, an activated carbon was prepared from Typha orientalis and then
      treated with KMnO(4) and used for the removal of Basic Violet 14 from aqueous
      solutions. KMnO(4) treatment influenced the physicochemical properties of the
      carbon and improved its adsorption capacity. Adsorption experiments were then
      conducted with KMnO(4)-modified activated carbon to study the effects of carbon
      dosage (250-1500 mg/L), pH (2-10), ion strength (0-0.5 mol/L), temperature, and
      contact time on the adsorption of Basic Violet 14 from aqueous solutions. The
      equilibrium data were analyzed by the Langmuir and Freundlich isotherms and
      fitted well with the Langmuir model. The pseudo-first-order, pseudo-second-order,
      and intraparticle diffusion models were used to evaluate the kinetic data and the
      pseudo-second-order kinetics was the best with good correlation.

PMID- 20036371
TI  - Electrical and morphological properties of conducting layers formed from the
      silver-glass composite conducting powders prepared by spray pyrolysis.
AB  - Ag-glass composite powders with various glass contents and excellent conducting
      properties were prepared by spray pyrolysis. Irrespective of the glass content,
      all the prepared powders were found to comprise spherical particles with
      nonaggregation characteristics. The crystal structure of the powder particles
      resembled that of pure Ag particles, irrespective of the glass content.
      Conducting layers formed from pure Ag did not melt even when sintered at 400
      degrees C. On the other hand, conducting layers formed from composite powders
      containing 3 and 5 wt% glass melted when sintered at 400 degrees C. The optimum
      glass content of the composite powders was 3 wt% at sintering temperatures of 400
      and 450 degrees C. However, the optimum glass content decreased to 1 wt% when the
      sintering temperature was increased to 550 degrees C. The lowest specific
      resistances of the conducting layers formed from the composite powders were 5.3
      and 2.3 microohms-cm at sintering temperatures of 400 and 550 degrees C,
      respectively.

PMID- 20036372
TI  - Azobenzene dye induced micelle to vesicle transition in cationic surfactant
      aqueous solutions.
AB  - A photo-responsive azobenzene dye, sodium 4-[(E)-phenyldiazenyl] benzoate
      (AZONa), was employed to induce microstructural changes with
      cetyltrimethylammonium bromide (CTAB) in aqueous solution. A spherical micelle to
      vesicle transition via wormlike micelles was investigated by employing turbidity,
      viscosity, and dynamic light scattering measurements, as well as cryo
      transmission electronic microscopy. At a certain molar ratio [AZONa]/[CTAB] of
      0.65 the zero-shear viscosity achieve a maximum, showing clearly the formation of
      wormlike micelles that obey the classic Maxwellian behavior at low shear
      frequencies. At this critical molar ratio, an increase in temperature resulted in
      the breakdown of wormlike micelles, whereas the viscosity eta(0) showed three
      domains of growth characterized by scaling laws as the surfactant concentration
      was varied between 10 and 40 mM. The rapid increase in eta(0) could be explained
      by an incomplete screening of electrostatic repulsions of the solution. The
      decrease in eta(0) was due to the formation of branched wormlike micelles above
      once a concentration [CTAB]=20 mM.

PMID- 20036373
TI  - Competitive adsorption involving phosphate and benzenecarboxylic acids on
      goethite--effects of molecular structures.
AB  - The competitive adsorption between phosphate and either one of seven
      benzenecarboxylates (benzoate, phthalate, trimellitate, trimesoate,
      hemimellitate, pyromellitate, and mellitate) on the surfaces of fine-particulate
      goethite (alpha-FeOOH) was investigated as a function of pH. The series of
      ligands contained molecules with an increasing number of functional groups as
      well as three structural isomers of the tricarboxylates. Thus, the effects of
      both the number of carboxylate groups and the relative positions of these groups
      on the competitive efficiency toward phosphate were probed in this study.
      Quantitative adsorption experiments in batch mode and infrared spectroscopy were
      collectively used to evaluate the competitive adsorption reactions. Under the
      conditions probed, mono- and dicarboxylates had no detectable effect on phosphate
      adsorption whereas the ligands containing three or more carboxylate groups were
      able to partially outcompete phosphate. However, the pH dependency and the extent
      of these competitive effects were strongly dependent on the structure and
      composition of the benzenecarboxylate. The collective results showed that it was
      the competition for hydrogen-bonding surface sites rather than inner sphere
      surface sites that primarily determined the outcome of the competitive adsorption
      experiments, and it was the ability of the organic ligand to act as hydrogen
      bonding acceptor and/or donor in various parts of the pH range that also
      determined the competitive pH dependency. The importance of H-bonding for the
      competitive adsorption between phosphate and benzenecarboxylic acids suggested
      that H-bonding interactions contributed substantially to the stabilities of both
      the adsorbed benzenecarboxylates and the phosphate ions and that these
      interactions were structurally specific; i.e., they were sensitive to the
      locations and the directional properties of the H-acceptor and H-donor surface
      sites.

PMID- 20036374
TI  - Effect of periodontitis on susceptibility to atrial fibrillation in an animal
      model.
AB  - BACKGROUND: Inflammation is implicated in the pathophysiology of atrial
      fibrillation (AF). Periodontitis causes a general inflammatory response. Whether
      periodontitis is related to AF is unknown. OBJECTIVE: The aim of the study was to
      test the hypothesis that inflammation facilitates AF. METHODS: Twenty-two adult
      mongrel canines of either sex were used for this study. Periodontitis was induced
      in 12 dogs (periodontitis group) by tying 2-0 silk ligatures at the second
      premolar of mandibula. Ten healthy dogs were used as controls. Before the
      ligation procedure and on the day 30, 60, and 90 after ligation, an
      electrophysiologic evaluation was performed to measure atrial refractoriness and
      AF inducibility by delivering a single atrial extrastimuli in the high right
      atrium, atrial septum (AS), and coronary sinus (CS), respectively. Before each
      electrophysiologic study, blood samples were taken for determining the levels of
      C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-alpha). Animals
      were killed after 90 days. The hearts and mandibulae were harvested for
      morphological study, and the periodontal disease severity was quanti fi ed.
      RESULTS: Atrial effective refractory period (AERP) shortened, and AF inducibility
      increased progressively in the periodontitis group. At a drive length of 300
      milliseconds, AERP in the CS was 126.7 +/- 13.0 milliseconds and 107.5 +/- 9.7
      milliseconds after 60 and 90 days of ligation, respectively (vs 165.8 +/- 10.8
      milliseconds at baseline; P < .001). By CS pacing, AF was induced in 5 and 10 of
      12 dogs on day 60 and 90 after ligation, respectively (vs 1/12 at baseline; P <
      .05 and P < .01, respectively). Elevation of CRP and TNF-alpha occurred after 60
      days of ligation (CRP, 13.42 +/- 2.21 mg/L vs control, 1.92 +/- 0.38 mg/L; P <
      .001; TNF-alpha, 9.85 +/- 1.72 mg/L vs control, 3.36 +/- 0.75 mg/L; P < .001) and
      reached the peak at the end of the study (CRP, 31.38 +/- 2.69 mg/L vs control,
      1.99 +/- 0.40 mg/L; P < .001; TNF-alpha, 12.32 +/- 1.07 mg/L vs control, 3.24 +/-
      0.53 mg/L; P < .001). There was a negative correlation between the levels of
      serum inflammatory factors and AERP values (P < .05). Alveolar bone level
      decreased in the periodontitis group (P < .001). The long axis (P < .001) of
      atrial cardiomyocytes including the right atrial appendage (25.50 +/- 3.58 microm
      vs 18.14 +/- 3.32 microm), AS (24.78 +/- 3.45 microm vs 17.47 +/- 2.57 microm),
      and left atrial appendage (31.90 +/- 4.80 microm vs 18.78 +/- 2.42 microm) from
      the periodontitis group was larger than the control group. The short axis of
      atrial cardiomyocytes was larger than the control group, too (P < .001).
      Inflammatory cells were more generally found in the atria of the periodontitis
      group (P < .001). Myolysis affected some atrial cardiomyocytes of the dogs with
      periodontitis. CONCLUSION: Periodontitis led to inflammatory responses in the
      atrial myocardium, which disturbed the structural and electrophysiologic
      properties of the atrium and facilitated AF.

PMID- 20036375
TI  - Fact or artifact? The electrocardiographic diagnosis of orthostatic tremor.
AB  - Orthostatic tremor is a rare but disabling neurologic condition characterized by
      unsteadiness when standing accompanied by rapid leg tremor and frequent falls. We
      present the case of a 57-year-old man who presented with a several-month history
      of falls and was found to have orthostatic tremor. Telemetry strips while
      standing revealed continuous gross 13 to 18 Hz of oscillatory artifact, identical
      to the frequency range of oscillations recorded with electromyographic recordings
      of the thigh muscles in patients with orthostatic tremor. If confirmed in other
      cases, electrocardiogram recorded in the standing position could become a simple
      noninvasive tool to screen for or to support the clinical diagnosis of
      orthostatic tremor.

PMID- 20036376
TI  - High flow nasal cannulae therapy in infants with bronchiolitis.
AB  - OBJECTIVES: To determine whether the introduction of heated humidified high-flow
      nasal cannulae (HFNC) therapy was associated with decreased rates of intubation
      for infants <24 months old with bronchiolitis admitted to a pediatric intensive
      care unit (PICU). STUDY DESIGN: A retrospective chart review of infants with
      bronchiolitis admitted before and in the season after introduction of HFNC.
      RESULTS: In the season after the introduction of HFNC, only 9% of infants
      admitted to the PICU with bronchiolitis required intubation, compared with 23% in
      the prior season (P=.043). This 68% decrease in need for intubation persisted in
      a logistic regression model controlling for age, weight, and RSV status. HFNC
      therapy resulted in a greater decrease in respiratory rate compared with other
      forms of respiratory support, and those infants with the greatest decrease in
      respiratory rate were least likely to be intubated. In addition, median PICU
      length of stay for children with bronchiolitis decreased from 6 to 4 days after
      the introduction of HFNC. DISCUSSION: We hypothesize that HFNC decreases rates of
      intubation in infants with bronchiolitis by decreasing the respiratory rate and
      work of breathing by providing a comfortable and well-tolerated means of
      noninvasive ventilatory support.

PMID- 20036377
TI  - Body size of twins compared with siblings and the general population: from birth
      to late adolescence.
AB  - OBJECTIVES: We examined whether and when differences in body size disappear over
      time and whether twins attain normal final height and body mass index (BMI).
      STUDY DESIGN: Height, weight, and BMI data of twins at ages 1, 4, and 18 years
      were compared with data from their nontwin siblings. Second, twin and sibling
      data were compared with population standards. In addition to height, weight, and
      BMI, data on body proportions at age 18 years were analyzed. RESULTS: At the age
      of 18 years, twins were as tall as their siblings but were significantly leaner.
      Compared with children from the general population, adolescent twins attained the
      same height and BMI. Birth weight was shown to have a considerable effect on
      height in adolescent twins. CONCLUSIONS: Twins attained normal final height
      compared with siblings and children from the general population. No differences
      in BMI were shown between 18-year-old twins and children from the general
      population, whereas the siblings of twins had increased BMI values compared with
      the general population.

PMID- 20036378
TI  - An exclusively human milk-based diet is associated with a lower rate of
      necrotizing enterocolitis than a diet of human milk and bovine milk-based
      products.
AB  - OBJECTIVE: To evaluate the health benefits of an exclusively human milk-based
      diet compared with a diet of both human milk and bovine milk-based products in
      extremely premature infants. STUDY DESIGN: Infants fed their own mothers' milk
      were randomized to 1 of 3 study groups. Groups HM100 and HM40 received
      pasteurized donor human milk-based human milk fortifier when the enteral intake
      was 100 and 40 mL/kg/d, respectively, and both groups received pasteurized donor
      human milk if no mother's milk was available. Group BOV received bovine milk
      based human milk fortifier when the enteral intake was 100 mL/kg/d and preterm
      formula if no mother's milk was available. Outcomes included duration of
      parenteral nutrition, morbidity, and growth. RESULTS: The 3 groups (total n = 207
      infants) had similar baseline demographic variables, duration of parenteral
      nutrition, rates of late-onset sepsis, and growth. The groups receiving an
      exclusively human milk diet had significantly lower rates of necrotizing
      enterocolitis (NEC; P = .02) and NEC requiring surgical intervention (P = .007).
      CONCLUSIONS: For extremely premature infants, an exclusively human milk-based
      diet is associated with significantly lower rates of NEC and surgical NEC when
      compared with a mother's milk-based diet that also includes bovine milk-based
      products.

PMID- 20036379
TI  - Preterm small for gestational age infants are not at higher risk for parenteral
      nutrition-associated cholestasis.
AB  - OBJECTIVE: To assess if being small for gestational age impacts parenteral
      nutrition-associated cholestasis (PNAC) development. STUDY DESIGN: We reviewed
      all the very low-birth weight infants exposed to parenteral nutrition for >14
      days from 1996 to 2006, comparing auxological and clinical data, as well as
      nutritional history, during the first 4 weeks of life of infants with cholestasis
      and control subjects. RESULTS: Of 445 very low-birth weight infants, 55 had
      development of PNAC. Infants with cholestasis had lower birth weight and
      gestational age but similar birth weight z-score compared with infants without
      cholestasis, and they received a lower amount of enteral feeds (25.8 +/- 20.7 vs
      67.9 +/- 33.0 mL/kg, P < .001), a greater amount of intravenous glucose (10.6 +/-
      1.3 vs 7.5 +/- 2.5 g/kg, P < .0001), lipids (1.8 +/- 0.4 vs 1.3 +/- 0.5, P <
      .0001) and proteins (2.7 +/- 0.5 vs 1.9 +/- 0.7, P < .0001), and needed a higher
      number of days of fasting (13.2 +/- 6.7 vs 6.5 +/- 4.8, P < .001). Enteral intake
      between 0 and 21 days of life (OR 0.66; 95% CI 0.53, 0.81, P < .0001) and oxygen
      therapy (OR 1.05; 95% CI 1.01, 1.09; P = .030) were identified as the best
      independent predictors of PNAC. CONCLUSIONS: Enteral feeding remains the main
      factor for the prevention of PNAC, whereas small for gestational age infants do
      not have a higher risk of PNAC.

PMID- 20036380
TI  - Bacterial overgrowth and methane production in children with encopresis.
AB  - OBJECTIVES: To assess the prevalence of small intestinal bacterial overgrowth
      (SIBO) and methane production in children with encopresis. STUDY DESIGN:
      Radiographic fecal impaction (FI) scores were assessed in children with
      secondary, retentive encopresis and compared with the breath test results. Breath
      tests with hypoosmotic lactulose solution were performed in both the study
      patients (n = 50) and gastrointestinal control subjects (n = 39) groups. RESULTS:
      The FI scores were significantly higher in the patients with encopresis who were
      methane producers (P < .01). SIBO was diagnosed in 21 of 50 (42%) patients with
      encopresis and 9 of 39 (23%) of control subjects (P = .06). Methane was produced
      in 56% of the patients with encopresis versus 23.1% of the control subjects in
      the gastrointestinal group (P < .01). Fasting methane level was elevated in 48%
      versus 10.3 %, respectively (P < .01). CONCLUSIONS: Children with FI and
      encopresis had a higher prevalence of SIBO, elevated basal methane levels, and
      higher methane production. Methane production was associated with more severe
      colonic impaction. Further study is needed to determine whether methane
      production is a primary or secondary factor in the pathogenesis of SIBO and
      encopresis.

PMID- 20036381
TI  - An assessment of the effects of a hyaluronan-based solution on reduction of
      postsurgical adhesion formation in rats: a comparative study of hyaluronan-based
      solution and two film barriers.
AB  - BACKGROUND: Intra-abdominal application of anti-adhesive barriers may reduce the
      extent and severity of postoperative adhesions. This study was designed to
      compare the effectiveness of a sprayable liquid barrier (a mixed solution of
      sodium hyaluronate and carboxymethylcellulose) with two conventional sheets.
      METHODS: Eighty male Sprague Dawley rats underwent laparotomy with subsequent
      multiple intestinal wall abrasions and abdominal wall injury. Afterwards, sodium
      hyaluronate and carboxymethylcellulose (HA-CMC) solutions were intraperitoneally
      sprayed or a film barrier of either oxidized regenerated cellulose (ORC) or
      polylactic acid (PA) was placed under the incision. At postoperative d 21, the
      rats underwent relaparotomy and complete adhesiolysis. Three investigators, who
      were blind to the group assignment, scored the extent of adhesion formation and
      resected specimens for histologic examination of fibrosis and inflammation.
      Expression profiles of parameters as mediators (macrophages [CD68]) in cellular
      inflammation response were analyzed. RESULTS: Mean adhesion scores in rats that
      received HA-CMC solution (7.6+/-2.3) and ORC membrane (8.1+/-2.2) were lower than
      in rats that received PA film (10.7+/-2.5) and the control group (11.2+/-2.6)
      (P<0.05 for each comparison). In addition, there were significantly fewer
      adhesions located between large and small intestine in the HA-CMC solution group
      than in the control and each of the film barrier groups (P<0.05 for each
      comparison). CONCLUSIONS: This study suggests that both HA-CMC solution and ORC
      membrane decrease the overall incidence of postoperative adhesions. However, the
      mixed solution of HA-CMC appeared to be superior to ORC membrane because this
      sprayable solution is easy to use and suitable for site-specific adhesion
      prevention after multifocal bowel trauma.

PMID- 20036382
TI  - Compartmental apoptosis and neutrophil accumulation in severe peritonitis.
AB  - BACKGROUND: Migration and activation of polymorphonuclear neutrophils (PMN) and
      apoptosis are central to inflammatory tissue damage. This study examines the
      relation of these processes, and their expression in the abdominal, systemic, and
      bronchoalveolar compartments in patients with severe peritonitis. MATERIALS AND
      METHODS: Thirty-one consecutive patients undergoing laparotomy for severe
      secondary peritonitis. Eight operated patients without peritonitis and 10 long
      term mechanically ventilated noninfected patients served as controls. Peritoneal
      fluid, blood, and bronchoalveolar lavage fluid (BALF) was obtained on d 0 (day of
      initial laparotomy), 2, and 3. Levels of chemokines (interleukin (IL)-8 and
      monocyte chemotactic protein (MCP)-1), PMN-counts, PMN activation
      [myeloperoxidase (MPO), elastase] and apoptosis (nucleosomes) were determined.
      RESULTS: In peritonitis patients, levels of chemokines and markers of PMN
      sequestration were increased in all compartments. IL-8 levels were higher in BALF
      than in plasma, and did not originate from the circulation or from lysis of
      alveolar cells. Pulmonary nucleosome levels were higher in patients who died
      (P=0.020), and corresponded with PMN-count in BALF (P<0.001), levels of
      chemokines (IL-8, P=0.003; MCP-1, P=0.001), and PMN-activation (MPO, P<0.001;
      elastase P=0.007). CONCLUSION: Severe peritonitis produces an early pulmonary
      expression of chemoattractants creating a gradient for PMN sequestration and
      activation into the lung. These parameters are associated with expression of
      apoptosis in the lung, which is increased in nonsurviving peritonitis patients.

PMID- 20036383
TI  - Protective effect of NAC preconditioning against ischemia-reperfusion injury in
      piglet small bowel transplantation: effects on plasma TNF, IL-8, hyaluronic acid,
      and NO.
AB  - BACKGROUND: Ischemia-reperfusion (I/R) injury is one of the main factors
      affecting the function and structure of small bowel transplantation (SBT), by
      generation of proinflammatory mediators such as reactive oxygen species, reactive
      nitrogen species, cytokines, and endotoxin. Experimental data have demonstrated
      that N-acetylcysteine (NAC) attenuates intestinal I/R injury. The objective of
      this study was to determine the effect of NAC preconditioning on the SBT-I/R
      induced inflammatory cascade, with particular focus on TNF, IL-8, hyaluronic
      acid, and NO. METHODS: Fifteen domestic pigs were used as donors. Fifteen
      recipient animals were randomly assigned into two groups. Group 1: SBTx (n=7)
      served as controls and Group 2: SBTx (n=8) served as the experimental group (NAC
      administration). RESULTS: NAC administration at a continuous 4 h intravenous
      bolus dose of 200 mg/kg of body weight, starting before initiation of bowel
      transplantation, resulted in statistically significant (P<0.05) higher plasma
      levels of NO, and lower plasma levels of hyaluronic acid, TNF-alpha, IL-8, and
      LDH compared with those of the control group, at the 360 min time point.
      CONCLUSIONS: NAC confers a protective role in small bowel transplantation
      associated, partly, with NO generation and hyaluronic acid, TNF-alpha and IL-8
      amelioration.

PMID- 20036385
TI  - Changes of plasma glutamine concentration and hepatocyte membrane system N
      transporters expression in early endotoxemia.
AB  - BACKGROUND: Glutamine plays important roles in health and critical illness.
      During endotoxemia, glutamine metabolism, including its plasma level and
      transport, changes markedly. Previous studies have demonstrated that system N
      transporters in hepatocytes play a major role in hepatic glutamine transport.
      However, little is known about the changes of mRNA and protein expression of
      system N transporters in hepatocyte plasma membrane. Furthermore, the alteration
      of plasma glutamine concentration during endotoxemia is still controversial. In
      this study, we investigated the changes in early endotoxemic rats by
      intraperitoneal injection of lipopolysaccharide (LPS). MATERIALS AND METHODS:
      Three, 6, 12 mg/kg body weight doses of LPS were injected intraperitoneally to
      establish the endotoxemic rat model; equal volume of 0.9% saline was used as the
      control. Before and 2, 4, 6, 12, 24h after injections, plasma glutamine
      concentration, mRNA, and protein expression of SNAT3 and SNAT5 transporters in
      hepatocyte plasma membrane were detected by high performance liquid
      chromatography, real-time PCR, and Western blot, respectively. RESULTS: LPS
      injection resulted in a marked increase of the plasma glutamine concentration
      from 4 to 12h (3mg/kg) and 2 to 6h (6 mg/kg, 12 mg/kg) after the injection
      compared with its physiologic level, and a significant decrease in 6, 12 mg/kg
      groups at 24h. Both the mRNA and protein expression of SNAT3 and SNAT5 were
      enhanced by LPS in a time- and dose-dependent manner. CONCLUSIONS: The plasma
      glutamine concentration in endotoxemic rat increased transiently during early
      endotoxemia but subsequently decreased over time. The effect of LPS on system N
      expression occurs not only at the protein level, but also at the mRNA level. It
      is reasonable to supplement glutamine for patients with sepsis or endotoxemia
      begin at 6 to 12h after the development of disease.

PMID- 20036384
TI  - P-selectin expression in cold preserved kidneys in University of Wisconsin and
      histidine-tryptophan-ketoglutarate solutions.
AB  - The differences and efficacy of standard preservation solutions in kidney
      transplantation, University of Wisconsin (UW) and histidine-tryptophan
      ketoglutarate (HTK), remain a topic of debate in recent clinical studies. P
      selectins represent glycoproteins expressed on endothelial cells and platelets
      responsible for the earliest events in ischemia/reperfusion injury in kidney
      transplantation. This study aimed to compare the levels of P-selectin expression
      between cold preserved kidney tissues in UW and HTK solutions. Thirty kidneys
      were procured from male Lewis rats and stored in cold (4 degrees C) solutions for
      periods of 4, 12, 16, 20, and 24h. Group 1 (n=15) kidneys were stored in UW
      solutions, and group 2 (n=15) kidneys were submerged in HTK solutions. At the end
      of each time point, the kidneys underwent preparation and levels of P-selectin
      expression in the tissues were measured using Immunoblot analyses and adjusted
      volumetric quantification of Western blot signals. For all periods of cold
      preservation, P-selectin expression was significantly down-regulated in kidney
      tissues stored in UW compared with HTK solutions (P<0.001). In summary, UW
      demonstrated a significant benefit over HTK solution in down-regulating P
      selectin expression in cold preserved kidney grafts.

PMID- 20036386
TI  - Systemic transplantation of progenitor cells accelerates wound epithelialization
      and neovascularization in the hairless mouse ear wound model.
AB  - BACKGROUND: Impaired wound healing due to local injury, infection, or systemic
      diseases, such as diabetes, is a major clinical problem. Recent studies have
      shown that endothelial progenitor cells (EPC) isolated from peripheral blood,
      bone marrow, as well as the spleen accumulate in granulation tissue at the site
      of neovascularization, causing secretion of growth factors and cytokines and thus
      accelerating wound healing. MATERIALS AND METHODS: In the present study, we
      transplanted systemic EPC and then measured epithelialization and
      neovascularization in the hairless mouse ear wound model. RESULTS: Systemic EPC
      transplantation significantly accelerated epithelialization and
      neovascularization compared with control wounds receiving phosphate-buffered
      saline without calcium and magnesium (PBS). The EPC group had significantly
      higher vascular density than did the PBS-treated group as determined by
      immunohistochemistry for CD31 and CD90. Fluorescence microscopy revealed
      accumulation "homing" of the transplanted EPC at the sites of neovascularization
      in the granulation tissue throughout healing. Furthermore, transplantation of EPC
      also increased the expression of the angiogenic cytokine stromal cell-derived
      factor 1alpha (SDF1alpha). CONCLUSIONS: This appears to be the first
      demonstration of EPC recruitment to the site of wound neovascularization
      throughout the healing process. These findings demonstrate that transplanting
      systemic EPC into "normal" healing wounds promotes epithelialization and
      neovascularization and thus could be an useful method for accelerating wound
      healing.

PMID- 20036387
TI  - Mammalian target of rapamycin signaling pathway contributes to glioma progression
      and patients' prognosis.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) pathway plays an important
      role in the regulation of cell growth and increasing evidence suggests its
      dysregulation in tumors. It also implements many other critical cellular
      functions, including protein degradation and angiogenesis. To date, a correlation
      between the mTOR pathway in human glioma and patients' prognosis has not been
      reported. METHODS: To address this question, we carried out an
      immunohistochemical study of the mTOR upstream and downstream targets
      phosphorylated Akt (pAkt), phosphorylated S6 ribosomal protein (pS6), and p27, as
      well as phosphatase and tensin homologue (PTEN) using biopsies from 96 patients
      with primary glioma. Kaplan-Meier survival and Cox regression analyses were
      performed to evaluate the prognosis of patients. RESULTS: Immunostaining revealed
      that the mTOR pathway was significantly associated with the Karnofsky performance
      scale (KPS) score and World Health Organization (WHO) grade of patients with
      glioma. Especially, the positive expression rates of pAkt, cytoplasmic p27, and
      pS6 were significantly higher in patients with higher grade (P = 0.002, 0.001 and
      0.002) and lower KPS score (P = 0.007, 0.005, and 0.008), which were opposite to
      the nuclear p27 and PENT expression. Statistical analysis showed that patients
      with glioma expressing pAkt, PTEN, cytoplasmic p27, nuclear p27, and pS6 have
      different overall survival rates relative to those not expressing these proteins.
      Cox multi-factor analysis showed that KPS (P = 0.02), WHO grade (P = 0.005), pAkt
      (P = 0.009), PTEN (P = 0.006), cytoplasm p27 (P = 0.008), nuclear p27 (P = 0.01),
      and pS6 (P = 0.003) were independent prognosis factors for human glioma.
      CONCLUSION: These results provide convincing evidence for the first time that the
      mTOR pathway correlated closely with overall survival of patients with glioma and
      might be a novel prognostic marker.

PMID- 20036388
TI  - Attenuation of propofol tolerance conferred by remifentanil co-administration
      does not reduce propofol toxicity in rabbits under prolonged mechanical
      ventilation.
AB  - BACKGROUND: Prolonged sedation with propofol at high doses may lead to fatal
      multi-organ dysfunction, know as propofol infusion syndrome. We tested the
      hypothesis that propofol plus remifentanil co-administration attenuates propofol
      tolerance to its sedative effect and assessed if such an effect has an impact on
      propofol toxicity in rabbits under prolonged mechanical ventilation. MATERIALS
      AND METHODS: Eighteen healthy male rabbits were mechanically ventilated and
      received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6),
      or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under
      sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h.
      Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed,
      to maintain the desired level of sedation and analgesia, respectively (groups P
      and PR). In group RS, remifentanil was infused at IRs equivalent to those of
      group PR. Propofol IRs were recorded, propofol concentrations were measured in
      the arterial plasma, and blood biochemical parameters and organ histopathology
      were assessed. RESULTS: Animals survived for 29-36 h in group P and 22-38 h in
      group PR (100% mortality rate). Tolerance was developed to propofol's sedative
      effect. The onset of tolerance was delayed and its magnitude was decreased in
      group PR compared with group P. Propofol was accumulated in the systemic
      circulation. Propofol clearance rate was gradually decreased. Arterial lactate,
      and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH),
      bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were
      increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and
      skeletal muscles were seriously injured in groups P and PR. In group RS,
      mortality was 0%, while there was only mild injury of the lungs, liver,
      gallbladder, kidneys, and urinary bladder. CONCLUSIONS: Although propofol
      tolerance is attenuated in propofol plus remifentanil receiving rabbits under
      prolonged mechanical ventilation, fatal multi-organ injury occurs resembling
      human propofol infusion syndrome.

PMID- 20036389
TI  - Abdominal adhesions: current and novel therapies.
AB  - An adhesion occurs when two tissues that normally freely move past each other
      attach via a fibrous bridge. Abdominal adhesions place a tremendous clinical and
      financial burden on public health. Adhesions develop after nearly every abdominal
      surgery, commonly causing female infertility, chronic pelvic pain, and, most
      frequently, small bowel obstruction. A National Hospital Discharge Survey of
      hospitalizations between 1998 and 2002 reported that 18.1% of hospitalizations
      were related to abdominal adhesions annually accounting for 948,000 days of
      inpatient care at an estimated cost of $1.18 billion. This review discusses the
      current or proposed therapies for abdominal adhesions. While many therapies for
      abdominal adhesions have been attempted, the need for a definitive therapy to
      prevent or even reduce abdominal adhesions still exists.

PMID- 20036390
TI  - In vitro schedule-dependent interaction between melphalan and oxaliplatin in
      human colorectal cancer cell lines.
AB  - OBJECTIVE: In order to determine the applicability of oxaliplatin in isolated
      liver perfusion, we identified the interaction between combinations of
      oxaliplatin and melphalan in 13 human colorectal cancer cell lines. METHODS:
      Cytotoxic activity was determined by the MTT-assay. Three different
      administration schedules of the two drugs were compared and median effect
      isobologram analysis was applied to the results, to determine the presence of
      synergism, additive effects, or antagonism as described by Chou and Talalay.
      RESULTS: Resistance to melphalan did not correspond to resistance to oxaliplatin.
      All combinations of melphalan and oxaliplatin showed synergistic or additive
      interaction in the majority of the cell lines. One hour of oxaliplatin followed
      by 1h of melphalan showed the lowest percentage of cell viability, with synergy
      in 10 out of 13 cell lines at 50% cell viability. Simultaneous treatment showed
      the highest cell viability, with antagonism in six cell lines, additivity in two
      cell lines, synergism in five cell lines at 50% cell viability. One hour of
      melphalan followed by 1h of oxaliplatin showed synergy in six cell lines,
      antagonism in another six, and additivity in one cell line. CONCLUSIONS: Our
      findings suggest a schedule-dependent synergistic interaction between melphalan
      and oxaliplatin. Therefore, oxaliplatin should be considered as a new,
      potentially valuable additional agent to the currently commonly used melphalan in
      isolated hepatic perfusion in colorectal cancer patients.

PMID- 20036391
TI  - Long-term follow-up study and comparison of meso-atrial shunts and meso-cavo
      atrial shunts for treatment of combined Budd-Chiari syndrome.
AB  - BACKGROUND: To investigate therapeutic effects of meso-atrial shunts (MASs) and
      meso-cavo-atrial shunt (MCASs) in combined Budd-Chiari syndrome (BCS). METHODS:
      We retrospectively gathered 29 cases of combined BCS with all or bilateral
      hepatic vein occlusion and long range occlusion or obstruction of inferior vena
      cava (IVC). Of them, 12 were treated with a MAS and 17 with a MCAS. We analyzed
      pre- and postoperative clinical symptoms, IVC, and portal venous (PV) pressure,
      occurrence rate of postoperative complications, patency rate of artificial
      vessels, and survival rate. RESULTS: One patient in the MAS group died in the
      preoperative period. During the follow-up period from 3 d to 60 mo, 96.6% were
      included. The effective rates were 54% in MAS and 90.8% in MCAS. The occurrence
      rates of postoperative complications were 12.5% and 1.8%, respectively. The
      average decreases in IVC and PV pressure were 15.5 mm saline and 62.4 mm saline
      for MAS, and 12.3 mm saline and 184.7 mm saline for MCAS. The survival rates at
      1, 3, and 5 y were 41.7%, 41.7%, and 16.7% for MAS, and 94.1%, 88.2%, and 82.4%
      for MCAS. The 5-y patency rates were 41.7% and 94.1%. Comparing these two groups,
      all of the studied factors, with the exception of PV pressure, were significantly
      different (P<0.05). Thus, the therapeutic effects of MCASs were better than those
      of MASs. CONCLUSION: MCAS can simultaneously relieve high IVC and PV pressure in
      combined BCS. Compared with MASs, MCASs showed a decreased postoperative
      complication rate, a higher 5-y survival and artificial vessel patency rate.

PMID- 20036392
TI  - Simplifying physiologic injury severity measurement for predicting trauma
      outcomes.
AB  - BACKGROUND: The Revised Trauma Score (RTS) is commonly used to assess physiologic
      injury; however its use is limited by missing data. This study compares different
      parameters of physiologic injury assessment in their ability to predict mortality
      after trauma. METHODS: Adult patients in the National Trauma Data Bank (NTDB
      version 7.0) were analyzed, and the following physiologic injury parameters were
      compared: RTS, systolic blood pressure (SBP), shock (SBP <or= 90 mm Hg), Glasgow
      coma scale-total (GCS-T), and GCS-motor (GCS-M). Areas under the receiver
      operating characteristic curves (AUROC) were calculated for unadjusted and
      multivariate regression models to predict mortality after trauma. RESULTS: There
      were 1,484,648 patients who met inclusion criteria. In unadjusted analyses, RTS
      had the highest proportion of missing data (21%) and was highly predictive of
      mortality (AUROC = 0.85). SBP and shock had a much lower AUROC of 0.67 and 0.66,
      respectively, but had many fewer missing cases. The combination parameters of GCS
      M with SBP or GCS-M with shock showed AUROC comparable to RTS (0.85) with
      approximately 80,000 fewer missing cases. CONCLUSION: The discriminatory power of
      RTS is significantly better than SBP, shock, or GCS alone. Given the limitation
      of missing data associated with RTS, the combination of SBP and GCS-M is a more
      reliable and equally effective method of assessing physiologic injury severity in
      studying trauma outcomes.

PMID- 20036393
TI  - Which hottest nodes can predict sentinel lymph node metastasis in breast cancer?
AB  - BACKGROUND: In approximately 80% of breast cancer patients, the hottest sentinel
      lymph nodes (SLNs) can be used to predict nodal metastasis. We correlate the
      reliability of using these nodes to predict SLN metastasis with different
      lymphoscintigraphic patterns in breast cancer. METHODS: SLN biopsies for T(1
      2)N(o) breast cancer were performed on 467 patients. Lymphoscintigraphic patterns
      were divided into three groups by the number of draining routes using blue dye
      and radiocolloid and whether the hottest nodes were the first nodes in the
      channel. RESULTS: The hottest SLNs detected 78 of 87 (90%) cases of SLN
      metastasis in the 399 patients with successful labeling of both blue dye and
      radiocolloid in their SLNs. False-negative rates were 0% (single-channel, first
      node), 58% (multi-channel, first node), and 71% (zero-channel, 0 hottest nodes)
      (FNR: SingleChanl versus ZeroChanl, P=0.005 and SingleChanl versus MultiChanl,
      P=0.037; Fisher's exact test). CONCLUSIONS: We recommend a preoperative
      lymphoscintigram to distinguish the subset of breast-cancer patients with a
      single draining channel and whose hottest node is the first node.

PMID- 20036394
TI  - Factors affecting number of lymph nodes harvested in colorectal cancer.
AB  - BACKGROUND: Lymph node involvement is a highly important prognostic factor in
      colorectal cancer staging. Examination of a minimum of 12 nodes is recommended
      for accurate staging. The purpose of this study was to identify factors affecting
      the number of lymph nodes harvested in colorectal cancer specimens. MATERIALS AND
      METHODS: Retrospective review of all patients undergoing colectomy for colorectal
      cancer at our VA hospital from 2002 to 2007 was done. Statistical analysis was
      done using univariate as well as multivariate analysis. One hundred eighty-three
      patients were analyzed. RESULTS: Average number of nodes retrieved was 14.9 with
      92 (51%) containing fewer than 12 lymph nodes. Median number of nodes was 11. The
      only two factors found to have an effect on nodes harvested were pathologist
      P<0.05 and surgeon experience P=0.01. Factors not found to have an impact on
      number of nodes harvested were age of patient, previous operation, T stage of
      tumor, type of colectomy, bowel prep, laparoscopic versus open technique, or BMI.
      Multivariate analysis confirmed pathologist and surgeon experience as independent
      factors associated with number of nodes retrieved P<0.05. CONCLUSIONS: Operating
      surgeon and examining pathologist were the only factors found to have a
      significant impact on number of nodes harvested. Meticulous dissection both in
      and outside of the operating room are indicated.

PMID- 20036395
TI  - A new survivable damage control model including hypothermia, hemodilution, and
      liver injury.
AB  - BACKGROUND: The purpose of this article is to describe a new model of traumatic
      intra-cavitary hemorrhage in a hypothermic, hemodiluted liver injury model that
      incorporates damage control principles and allows for survival. MATERIALS AND
      METHODS: Twenty swine underwent a standardized 35% blood volume hemorrhage
      followed by resuscitation. Ten animals sustained nonsurgical and 10 a surgical
      high-grade liver injury. In the surgical liver injury, damage control gauze
      packing was performed. No operative treatment was provided for the nonsurgical
      liver injury, which was designed to test the efficacy of systemic hemostatic
      agents. After a 15 min treatment phase, the abdominal cavity was closed, with the
      packing in place for the surgical injury, and all animals were resuscitated.
      Necropsy was performed at 48 h post-injury. RESULTS: At the time of liver injury,
      the animals were hemodiluted and hypothermic. Both injuries caused a 20% drop in
      the mean arterial pressure from baseline (P<0.001). Comparing baseline
      thromboelastography results with the results after hemodilution, hypothermia, and
      liver injury, a hypercoagulopathic state was observed. Mortality was 30% for both
      types of liver injury. The mean volume of intra-abdominal blood present at
      autopsy was similar for both types of liver injuries (202 +/- 161 mL and 214 +/-
      203 mL, respectively). CONCLUSION: A new model of traumatic intra-cavitary
      hemorrhage in a hypothermic, hemodiluted liver injury model with damage control
      that allows for survival has been described. The mortality rate of 30% allows for
      the comparison of therapeutic interventions that may lead to improved survival.

PMID- 20036396
TI  - Plateau and transpulmonary pressure with elevated intra-abdominal pressure or
      atelectasis.
AB  - BACKGROUND: ARDSnet standards limit plateau pressure (Pplat) to reduce ventilator
      induced lung injury (VILI). Transpulmonary pressure (Ptp) [Pplat-pleural pressure
      (Ppl)], not Pplat, is the distending pressure of the lung. Lung distention can be
      affected by increased intra-abdominal pressure (IAP) and atelectasis. We
      hypothesized that the changes in distention caused by increases in IAP and
      atelectasis would be reflected by Ptp but independent of Pplat. METHODS: In
      Yorkshire pigs, esophageal pressure (Pes) was measured with a balloon catheter as
      a surrogate for Ppl under two experimental conditions: (1) high IAP group (n=5),
      where IAP was elevated by CO2 insufflation in 5 mm Hg steps from 0 to 30 mm Hg;
      and (2) Atelectasis group (n=5), where a double lumen endotracheal tube allowed
      clamping and degassing of either lung by O2 absorption. Lung collapse was
      estimated by increases in pulmonary shunt fraction. RESULTS: High IAP: Sequential
      increments in IAP caused a linear increase in Pplat (r2=0.754, P<0.0001). Ptp did
      not increase (r2=0.014, P=0.404) with IAP due to the concomitant increase in Pes
      (r2=0.726, P<0.0001). Partial Lung Collapse: There was no significant difference
      in Pplat between the atelectatic (21.83+/-0.63 cm H2O) and inflated lung (22.06+/
      0.61 cmH2O, P<0.05). Partial lung collapse caused a significant decrease in Pes
      (11.32+/-1.11 mm Hg) compared with inflation (15.89+/-0.72 mm Hg, P<0.05)
      resulting in a significant increase in Ptp (inflated=5.97+/-0.72 mm Hg;
      collapsed=10.55+/-1.53 mm Hg, P<0.05). CONCLUSIONS: Use of Pplat to set
      ventilation may under-ventilate patients with intra-abdominal hypertension and
      over-distend the lungs of patients with atelectasis. Thus, Ptp must be used to
      accurately set mechanical ventilation in the critically ill.

PMID- 20036397
TI  - [Hospital admissions for meningococcal infections in Madrid, Spain (1997-2005)].
AB  - BACKGROUND AND OBJECTIVES: Neisseria meningitidis infection causes an important
      morbidity and mortality in Spain. Our study aims to estimate the burden of
      hospital admissions for meningococcal infection in Spain during a nine-year
      period (1997-2005) by analyzing the Spanish hospital surveillance system.
      METHODS: An epidemiological retrospective study was conducted. Data were obtained
      from the national surveillance system for hospital data (Conjunto Minimo Basico
      de Datos) maintained by the Ministry of Health. Information about
      hospitalizations, age, length of stay in hospital, mortality and cost per patient
      was obtained. RESULTS: There were 1137 hospital discharges for meningococcal
      disease (International Classification of Diseases 9th Clinical Modification: ICD
      9 CM code 036 in any listed diagnosis) during the study period. Annual incidence
      was 2.41 cases per 100,000 individuals. Mortality rate and case-fatality rate
      were 0.19 cases per 100,000 population and 7.7%, respectively. The average length
      of hospitalization was 12 days. The youngest age group showed the highest
      hospitalizations incidence (24.42 hospitalizations per 100,000 population in
      those under 4 years of age) but the case-fatality rate was higher in the oldest
      group (11% in patients over 30 years). These hospitalizations imply an annual
      cost of 592,980 euro to the Madrid Health System. CONCLUSIONS: Our study shows
      that meningococcal infection is still an important cause of hospital admissions
      and mortality in Madrid, resulting in a high cost to the Health Care System.

PMID- 20036398
TI  - [Treatment approach of hepatocellular carcinoma in Spain. Analysis of 705
      patients from 62 centers].
AB  - BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) is the leading cause of
      death in patients with cirrhosis and its current situation in Spain is not well
      known. Therefore, a national registry was created to assess the characteristics
      of patients with de novo HCC. PATIENTS AND METHOD: Between 1/10/2008 and
      31/1/2009, 62 centers reported the baseline demographic, clinical and tumor
      characteristics, the first choice of treatment and eligibility for
      transplantation (OLT) of HCC diagnosed during this time. RESULTS: There were 705
      new cases of HCC, 78% men, mean age 65 years, 89% cirrhosis (58% Child-Pugh class
      A, 42% HCV, 30% alcohol). Only 334 cases (47%) were diagnosed by screening. The
      size of the main nodule and BCLC stage were significantly lower in the screening
      group than in the rest (p<0.001). The applicability of radical therapies
      (resection and percutaneous ablation) was significantly higher (47.5% versus
      24.6%, p<0.001) as well as the evaluation for OLT (31% versus 12%, p<0.001). The
      screening did not differ according to gender (p=0.204) or age (<50 years, <65,
      <75, >75 years) (p=0.171). Chemoembolization was the most common treatment:
      initial tumors (46.4%), tumors >5 cm (15.7%), multifocal HCC (37.9%) and as a
      bridge to OLT (33%). CONCLUSION: The majority of HCC patients are diagnosed in
      Spain out of early detection programs, and this limits the chance for early
      diagnosis and effective therapy.

PMID- 20036399
TI  - [Pathophysiology of CADASIL disease].
AB  - The pathogenic mechanism underlying Cerebral Autosomal Dominant Artheriopathy
      with Subcortical Infarcts and Leukoencephalopathy (CADASIL) remains elusive
      although the disease is well characterized at clinical, histological and genetic
      level. The conservation of the Notch pathway among species allowed the
      development of several animal and cellular models in order to study it. This
      review analyzes the reliability of the 7 pathogenic models raised for CADASIL
      disease: autoimmune origin, mitochondrial dysfunction, loss of Notch3 function,
      granular osmiophilic material (GOM) toxicity and long term unfolded protein
      response (UPR) activation. Besides, the relationship between vascular smooth
      muscle cells (VSMC) degeneration, ischemic lesions and symptoms are discussed.
      Lastly, some theories are pointed that would explain the exclusiveness of
      clinical expression to the neural system, being in fact a systemic artheriopathy.

PMID- 20036400
TI  - [Innovation in the health area].

PMID- 20036401
TI  - [Indications of non-invasive mechanical ventilation: what's the literature
      evidence?].
AB  - The progressive introduction of non-invasive mechanical ventilation (NIMV) in the
      management of respiratory failure has increased the number of clinical
      indications and has reduced common complication of conventional mechanical
      ventilation. Results of the technique are variable depending on the disease that
      causes the respiratory failure. With the purpose of reviewing studies about the
      use of NIMV and to report levels of evidence, different scientific societies have
      elaborated consensus conferences to establish the utility of NIMV in different
      indications.

PMID- 20036402
TI  - [Long-term prognosis of serum and urine n-terminal proBNP levels and glomerular
      filtration rate in heart failure patients].
AB  - BACKGROUND AND OBJECTIVE: The amino-terminal pro-brain natriuretic peptide (NT
      proBNP) and estimated glomerular filtration rate (eGFR) values are related to
      short prognosis in patients with heart failure (HF). This study evaluates the
      prognostic power of serum and urinary NT-proBNP levels, and eGFR values, in HF
      patients during a 60-month follow-up. PATIENTS AND METHODS: We studied 93 HF
      outpatients (66 males, age 65+/-12). Primary endpoint was defined as
      cardiovascular mortality and secondary endpoint as cardiovascular mortality or
      admissions. RESULTS: Only serum NT-proBNP levels had a significant area under the
      curve for the prognosis of 60-month mortality and combined events, 0.70 (p=0.004)
      and 0.67 (p=0.019), respectively. Urinary NT-proBNP and eGFR did not have
      statistical significant areas under the curve. Patients with high serum NT-proBNP
      had the highest risk of cardiovascular death [44 (IC 95% 38-50) vs. 56 (IC 95% 53
      59) months, p=0.0006] and combined events [33 (IC 95% 28-38) vs. 42 (IC 95% 28
      38) months; p=0.027]. After the integration of serum NT-proBNP and renal
      function, patients with high peptide levels and low eGFR had the worst survival
      [42 (IC 95% 33-52) months; p=0.010]. Finally, only serum NT-proBNP concentration
      above 933 pg/mL was a predictor of poor survival (hazard ratio=2.81, p=0.033) and
      NT-proBNP above 550 pg/mL for combined events (hazard ratio=1.79, p=0.049).
      CONCLUSIONS: Serum NT-proBNP levels were superior to urine NT-proBNP and eGFR
      values for predicting 60-month cardiovascular death and combined events in HF
      patients.

PMID- 20036403
TI  - [Estimated prevalence of chronic renal failure among patients with type 2
      diabetes in Spain].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to estimate the current
      prevalence of Chronic Renal Insufficiency (RI) in ambulatory patients with type 2
      Diabetes (T2DM) assisted in Endocrinology Departments all over Spain. PATIENTS
      AND METHODS: This was an observational, cross sectional, multicenter study. From
      each participant the following data were retrospective collected: demographic,
      anthropometric, renal function, diabetes, cardiovascular risk factors,
      comorbidities and treatment. RI was defined by a glomerular filtration rate lower
      than 60ml/min/1.73m(2), using the shortened MDRD method. RESULTS: 541 patients
      with T2DM were included, 53% were men, the mean age (DS) was 63 years old (7.9)
      and the HbA(1)c was 7.6 % (1.3). The prevalence (CI95%) of RI was 22.9% (19.4
      26.7), higher than the previous estimate, witch was 5,7% (3.9-8.0, p<0,0001). The
      associated risk factor for RI were age (OR 2.07; 95%CI: 1.47-2.91 per each ten
      year period of increase), female gender (OR 2.25; 95%CI: 1.36-3.71) and
      hyperuricemia (OR 3.15; 95% CI: 1.56-6.37). There were no differences in the
      metabolic control between patients with RI vs those without RI. CONCLUSIONS:
      22.9% of T2DM ambulatory patients followed by endocrinologist had RI, but just a
      quarter of them had previously been diagnosed. The automated determination of
      creatinine clearance could increase the proportion of diagnosis and facilitate
      the improvement of the metabolic control in these patients.

PMID- 20036404
TI  - Substrate utilization during exercise and recovery at moderate altitude.
AB  - Recent studies have shown that exercise training at moderate altitude or in
      moderate hypoxia improved glycemic parameters. From these data, it has been
      supposed that endurance exercise in moderate hypoxia affects substrate
      utilization and that exposure to moderate hypoxia in combination with exercise
      may be utilized as part of metabolic or diabetes prevention program. However, the
      influence of exercise at moderate hypoxia on circulating metabolites and hormones
      in terms of substrate utilization is unclear. The purpose of this study was to
      elucidate the influence of exercise in moderate hypoxia on substrate utilization.
      We determined cardiorespiratory, metabolic, and hormonal parameters during
      exercise and postexercise recovery at a simulated moderate altitude of 2000 m,
      and then we compared these variables with values obtained at sea level. Seven men
      participated in this study; subjects reported to the laboratory on 4 occasions.
      Two maximal exercise tests were performed to estimate peak oxygen uptake at the
      simulated 2000-m altitude and sea level on different days. Afterward, submaximal
      exercise tests were carried out at a simulated altitude of 2000 m or sea level,
      separated by 1 week. Subjects performed submaximal exercise at the same relative
      exercise intensity (50% peak oxygen uptake) at a simulated altitude of 2000 m and
      at sea level for 30 minutes. The tests were performed in random order, and
      subjects were blinded to the respective altitudes. Venous blood samples and
      expired gases were obtained before, during exercise (15 and 30 minutes), and
      during postexercise recovery periods (15, 30, 45, and 60 minutes). The
      respiratory exchange ratio during exercise and recovery at moderate altitude was
      greater than at sea level. The epinephrine and norepinephrine concentrations
      during exercise and recovery were higher (P < .05) at moderate altitude than at
      sea level. Free fatty acids and glycerol concentrations during recovery were
      lower (P < .05) at moderate altitude than at sea level. These results suggest
      that carbohydrate utilization is increased during exercise and postexercise
      recovery period in moderate hypoxia as compared with normoxia. It is also
      suggested that moderate hypoxia influences the changes in circulating metabolites
      and hormones in terms of substrate metabolism during exercise and the recovery.

PMID- 20036405
TI  - Aporphine and bisaporphine alkaloids from Aristolochia lagesiana var. intermedia.
AB  - Corydines, isocorydines, and analogous aporphine alkaloids were isolated from the
      leaves of Aristolochia lagesiana var. intermedia, together with three
      bisaporphine salts (lagesianines B-D). Their structures were determined by
      chemical derivatizations and spectroscopic analyses. Lagesianines B and C are the
      first examples of N-CH(2)-N' and C-2-O-C-1' linked dimeric aporphine alkaloids,
      respectively, while the monomeric units of lagesianine D, which has a carbon
      skeleton, are linked through C-7-C-5'via an ethane-1,2-diol group (C-7-CHOHCHOH-C
      5').

PMID- 20036406
TI  - Public health governance: views of key stakeholders.
AB  - OBJECTIVES: To identify views of key stakeholders on public health governance.
      STUDY DESIGN: Focus groups and interviews. METHODS: Key national and regional
      stakeholders in England were invited to participate in focus groups. Three focus
      groups and four additional interviews were transcribed and a thematic analysis
      was carried out. RESULTS: Focus groups and interviewees identified points of
      transition in public health governance including changes in the notion of
      stewardship, governance across a local public health system and a shift from
      organizational governance to 'governance of place'. CONCLUSIONS: Different
      governance arrangements and approaches to governance can influence health
      outcomes through their impact on commissioning strategies, public health practice
      and performance management regimes. Failure to address these issues will hamper
      the development of a stewardship role in local organizations and across a local
      public health system.

PMID- 20036407
TI  - Impact of education, income and chronic disease risk factors on mortality of
      adults: does 'a pauper-rich paradox' exist in Latin American societies?
AB  - OBJECTIVES: To test the hypothesis that an inverse association exists between
      socio-economic position and all-cause mortality in a developing country in Latin
      America. STUDY DESIGN: Prospective cohort study carried out in Chile using data
      from a simple random sample of 920 apparently healthy subjects (weighted
      population 11,600 aged 30-89 years) followed for 8 years. METHODS: Education
      level (0-8 years, 9-12 years and > or = 13 years) and income quartiles were
      established at the outset of the study, along with behavioural and biological
      risk factors for chronic diseases: smoking, alcohol use, obesity, diabetes,
      hypertension, lipids and family history of death by cardiovascular disease.
      Relative risks of all-cause mortality were estimated using age-adjusted Cox
      regression models. RESULTS: During the follow-up period, 46 deaths were observed.
      Adjusting for age, gender, and behavioural and biological risk factors, the
      mortality risk for increasing categories of education after controlling for
      income was 1.0, 0.76 and 0.33 (P for trend<0.01). In contrast, the relative risk
      for increasing levels of income after controlling for education was 1.0, 0.98,
      1.33 and 1.17 (P for trend=0.07). CONCLUSION: While education level had a
      protective effect on mortality risk of Chilean adults, income had a slightly
      unfavourable effect on survival. This finding is described as suggestive of a
      'pauper-rich paradox', since the higher income quantiles in this study correspond
      with the lower income levels in most developed countries. Nevertheless, due to
      the small number of deaths, additional research is required to assess the
      validity of these findings.

PMID- 20036408
TI  - [A novel mutation in ATP7B gene associated with severe neurological impairment in
      Wilson's disease].

PMID- 20036410
TI  - Temperature as an alternative tracer for the determination of the mixing
      characteristics in wastewater treatment plants.
AB  - The hydraulic characteristics, i.e. the residence time distributions, of
      wastewater treatment plant reactors are usually determined using conventional
      tracers. This paper aims to present an alternative approach based on wastewater
      temperature. The step in temperature change, e.g. from stormwater events with
      cold rainwater, is used as a tracer signal. The method was verified using lab-
      and pilot-scale tests that showed very good agreement of the time series
      estimated both with conventional and temperature tracer methods. Results from lab
      scale tests exhibit a zone with a minor water exchange of about 10% of the volume
      of all reactors, while the respective zone in the pilot-scale tests was estimated
      at about 30% of the total volume. The short-circuit flow was more than 50% of the
      inflow resulting from gaps between the walls inside the reactor cascade. An
      application example shows the importance of reliable residence time distribution
      underlying activated sludge modelling and the uncertainty associated with
      neglecting the determination of appropriate flow-through characteristics.

PMID- 20036409
TI  - Gp15 and gp16 cooperate in translocating bacteriophage T7 DNA into the infected
      cell.
AB  - Loss of up to four amino acids from the C terminus of the 1318 residue
      bacteriophage T7 gp16 allows plaque formation at normal efficiencies. Loss of
      five residues results in non-infective virions, and loss of twelve prevents
      assembly of stable particles. However, replacing the C-terminal seven with
      nineteen non-native residues allows assembly of non-infective virions. The latter
      adsorb and eject internal core proteins into the cell envelope but no phage DNA
      enters the cytoplasm. Extragenic suppressors of the defective gene 16 lie in gene
      15; the mutant gp15 proteins not only re-establish infectivity, they fully
      restore the kinetics of genome internalization to those exhibited by wild-type
      phage. After ejection from the infecting particle, gp15 and gp16 thus function
      together in ratcheting the leading end of the T7 genome into the cytoplasm of the
      infected cell.

PMID- 20036411
TI  - Characterization and inactivation of an agmatine deiminase from Helicobacter
      pylori.
AB  - Helicobacter pylori encodes a potential virulence factor, agmatine deiminase
      (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine
      (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an
      endogenous human cell signaling molecule that triggers the innate immune response
      in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that
      inhibition of this enzyme would increase the levels of agmatine, and thereby
      enhance the innate immune response. Taken together, these facts suggest that
      HpAgD is a potential drug target. Herein we describe the optimized expression,
      isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic
      characterization of this enzyme has also been performed. Additionally, the
      crystal structure of wild-type HpAgD has been determined at 2.1A resolution. This
      structure provides a molecular basis for the preferential deimination of
      agmatine, and identifies Asp198 as a key residue responsible for agmatine
      recognition, which has been confirmed experimentally. Information gathered from
      these studies led to the development and characterization of a novel class of
      haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD
      inhibitors ever described.

PMID- 20036412
TI  - Oxidative stress response and gene expression with atrazine exposure in adult
      female zebrafish (Danio rerio).
AB  - Atrazine (ATZ) is the most common pesticide of freshwater ecosystems in the
      world. The effects of ATZ exposure on the induction of oxidative stress and the
      alteration of gene expression were studied in liver and ovary samples from female
      zebrafish (Danio rerio). Antioxidant enzyme activities (SOD and CAT), in addition
      to the GSH and MDA content, in the liver altered significantly; the mRNA levels
      for the genes encoding these antioxidant proteins, such as Cu/Zn-Sod, Mn-Sod,
      Cat, and Gpx, were up-regulated significantly in the liver when zebrafish were
      exposed to various concentrations of ATZ for 14d. However, the mRNA induction
      patterns were not in accordance with those of antioxidant enzyme changes in the
      liver and ovary. Moreover, the transcriptional expression of mitochondrial inner
      membrane genes related to ROS production, such as Ucp-2 and Bcl-2, were altered
      significantly in high ATZ treatment groups. However, the ATZ treatment did not
      induce any apparent changes in the transcriptional expression of CoxI, Ndi, or
      ATPo6, which are related to the mitochondrial respiratory chain and ATP
      synthesis. To our knowledge, this is the first report to study the
      transcriptional effects of ATZ stress on zebrafish. The information presented in
      this study will be helpful in fully understanding the mechanism of oxidative
      stress induced by ATZ in fish.

PMID- 20036413
TI  - Effects of enhanced UV-B radiation on the distribution of mineral elements in
      soybean (Glycine max) seedlings.
AB  - In order to understand the effect of ultraviolet-B (UV-B) radiation on plant, the
      accumulated amount of dry matter and the distribution of the mineral elements in
      the different organs of soybean seedlings treated with UV-B radiation were
      investigated using the inductively coupled plasma-atomic emission spectrometry
      (ICP-AES). The results indicated that the accumulated amount of dry matter in
      root, stem and leaf of soybean seedlings treated with UV-B radiation during the
      stress and recovery period was lower than that of the control soybean. Moreover,
      the content of macroelements in the root, stem and leaf of soybean seedlings
      during the stress period and recovery period were decreased comparing with that
      of the control soybean. The change in the contents of microelements depended on
      the intensity of UV-B radiation, the organs of soybean and the treating period.
      Finally, the results from the stepwise regression analysis indicated that the
      content of specific microelements also affected the accumulation of dry matter in
      the soybean seedlings treated with UV-B radiation comparing with the contents of
      macroelements in the control soybean. The relationship between the contents of
      mineral elements and the accumulation of dry matter depended on the intensity of
      UV-B radiation and the organs of soybean. These results demonstrated that UV-B
      radiation induced the change in the distribution of mineral elements in root,
      stem and leaf, leading to the decrease in the accumulation of dry matter and then
      the inhibition of soybean growth. It was a possible effect mechanism of UV-B
      radiation on plant.

PMID- 20036414
TI  - A hominoid distal tibia from the Miocene of Pakistan.
AB  - A distal tibia, YGSP 1656, from the early Late Miocene portion of the Chinji
      Formation in Pakistan is described. The fossil is 11.4 million years old and is
      one of only six postcranial elements now assigned to Sivapithecus indicus.
      Aspects of the articular surface are cercopithecoid-like, suggesting some
      pronograde locomotor activities. However, YGSP 1656 possesses an
      anteroposteriorly compressed metaphysis and a mediolaterally thick medial
      malleolus, ape-like features functionally related to orthograde body postures and
      vertical climbing. YGSP 1656 lacks specializations found in the ankle of
      terrestrial cercopithecoids and thus Sivapithecus may have been primarily
      arboreal. Nevertheless, the morphology of this tibia is unique, consistent with
      other interpretations of Sivapithecus postcranial functional morphology that
      suggest the locomotion of this ape lacks a modern analog. Based on the limited
      postcranial remains from S. indicus, we hypothesize that this taxon exhibited
      substantial body size dimorphism.

PMID- 20036415
TI  - Chemically-speciated on-road PM(2.5) motor vehicle emission factors in Hong Kong.
AB  - PM(2.5) (particle with an aerodynamic diameter less than 2.5microm) was measured
      in different microenvironments of Hong Kong (including one urban tunnel, one Hong
      Kong/Mainland boundary roadside site, two urban roadside sites, and one urban
      ambient site) in 2003. The concentrations of organic carbon (OC), elemental
      carbon (EC), water-soluble ions, and up to 40 elements (Na to U) were determined.
      The average PM(2.5) mass concentrations were 229+/-90, 129+/-95, 69+/-12, 49+/
      18microg m(-3) in the urban tunnel, cross boundary roadside, urban roadside, and
      urban ambient environments, respectively. Carbonaceous particles (sum of organic
      material [OM] and EC) were the dominant constituents, on average, accounting for
      approximately 82% of PM(2.5) emissions in the tunnel, approximately 70% at the
      three roadside sites, and approximately 48% at the ambient site, respectively.
      The OC/EC ratios were 0.6+/-0.2 and 0.8+/-0.1 at the tunnel and roadside sites,
      respectively, suggesting carbonaceous aerosols were mainly from vehicle exhausts.
      Higher OC/EC ratio (1.9+/-0.7) occurred at the ambient site, indicating
      contributions from secondary organic aerosols. The PM(2.5) emission factor for on
      road diesel-fueled vehicles in the urban area of Hong Kong was 257+/-31mg veh(-1)
      km(-1), with a composition of approximately 51% EC, approximately 26% OC, and
      approximately 9% SO(4)(=). The other inorganic ions and elements made up
      approximately 11% of the total PM(2.5) emissions. OC composed the largest
      fraction (approximately 51%) in gasoline and liquid petroleum gas (LPG)
      emissions, followed by EC (approximately 19%). Diesel engines showed higher
      emission rates than did gasoline and LPG engines for most pollutants, except for
      V, Br, Sb, and Ba.

PMID- 20036416
TI  - Immunomodulator therapy: monoclonal antibodies, fusion proteins, cytokines, and
      immunoglobulins.
AB  - The immune system consists of a diverse array of immunocompetent cells and
      inflammatory mediators that exist in complex networks. These components interact
      through cascades and feedback circuits, maintaining physiologic inflammation (eg,
      tissue repair) and immunosurveillance. In various autoimmune and allergic
      diseases, a foreign antigen or autoantigen might upset this fine balance, leading
      to dysregulated immunity, persistent inflammation, and ultimately pathologic
      sequelae. In recent years, there has been tremendous progress delineating the
      specific components of the immune system that contribute to various aspects of
      normal immunity and specific disease states. With this greater understanding of
      pathogenesis coupled with advances in biotechnology, many immunomodulatory agents
      commonly called "biologic agents" have been introduced into the clinic for the
      treatment of various conditions, including immune globulins and cytokines. The 2
      most common classes of approved biologic agents are mAbs and fusion proteins with
      exquisite specificity. These agents have the potential both to optimize outcomes
      through more thorough modulation of specific parts of the dysregulated immune
      response and to minimize toxicity compared with less specific methods of
      immunosuppression.

PMID- 20036417
TI  - How to study placental vascular development?
AB  - Both exogenous and endogenous factors during pregnancy may impact placental
      vascular development and cause different malformations of placental vessels. In
      humans, consequences of abnormal vascular development have been associated with
      different pregnancy-related pathologies ranging from miscarriage to intrauterine
      growth restriction or preeclampsia. Pregnancy-associated exposure to bacterial or
      viral infections or pharmacologic or toxic agents may also influence vascular
      development of the placenta and lead to preterm labor and delivery. Several steps
      of vascular adaptation on both the fetal and maternal side are necessary and
      include such events as uterine vasodilation, remodeling by extravillous
      trophoblast, as well as vasculogenesis and angiogenesis within the placenta.
      Ubiquitous as well as pregnancy-specific angiogenic factors are involved.
      Morphologic and stereologic approaches, as well as experiments in established
      laboratory animals, cannot be applied to large domestic animals or humans without
      hesitation. Thus, further studies into the different aspects of this process will
      require an appropriate in vitro model of placental vascular development.
      Reflecting the core of placental vascular development, the in vitro model should
      facilitate the interactions between trophoblast and stromal cells with
      endothelial progenitor cells. The effects of viral or bacterial infection as well
      as pharmacologic or toxic agents may be studied more closely in the process. This
      report reviews major aspects of vascular development in the placenta and
      describes the establishment of a three-dimensional in vitro model of human
      placental vascular development.

PMID- 20036418
TI  - Surface deterioration of dental materials after simulated toothbrushing in
      relation to brushing time and load.
AB  - OBJECTIVES: (1) To evaluate the changes in surface roughness and gloss after
      simulated toothbrushing of 9 composite materials and 2 ceramic materials in
      relation to brushing time and load in vitro; (2) to assess the relationship
      between surface gloss and surface roughness. METHODS: Eight flat specimens of
      composite materials (microfilled: Adoro, Filtek Supreme, Heliomolar; microhybrid:
      Four Seasons, Tetric EvoCeram; hybrid: Compoglass F, Targis, Tetric Ceram;
      macrohybrid: Grandio), two ceramic materials (IPS d.SIGN and IPS Empress
      polished) were fabricated according to the manufacturer's instructions and
      optimally polished with up to 4000 grit SiC. The specimens were subjected to a
      toothbrushing (TB) simulation device (Willytec) with rotating movements,
      toothpaste slurry and at three different loads (100g/250g/350g). At hourly
      intervals from 1h to 10h TB, mean surface roughness Ra was measured with an
      optical sensor and the surface gloss (Gl) with a glossmeter. Statistical analysis
      was performed for log-transformed Ra data applying two-way ANOVA to evaluate the
      interaction between load and material and load and brushing time. RESULTS: There
      was a significant interaction between material and load as well as between load
      and brushing time (p<0.0001). The microhybrid and hybrid materials demonstrated
      more surface deterioration with higher loads, whereas with the microfilled resins
      Heliomolar and Adoro it was vice versa. For ceramic materials, no or little
      deterioration was observed over time and independent of the load. The ceramic
      materials and 3 of the composite materials (roughness) showed no further
      deterioration after 5h of toothbrushing. Mean surface gloss was the parameter
      which discriminated best between the materials, followed by mean surface
      roughness Ra. There was a strong correlation between surface gloss and surface
      roughness for all the materials except the ceramics. The evaluation of the
      deterioration curves of individual specimens revealed a more or less synchronous
      course suspecting hinting specific external conditions and not showing the true
      variability in relation to the tested material. SIGNIFICANCE: The surface
      roughness and gloss of dental materials changes with brushing time and load and
      thus results in different material rankings. Apart from Grandio, the hybrid
      composite resins were more prone to surface changes than microfilled composites.
      The deterioration potential of a composite material can be quickly assessed by
      measuring surface gloss. For this purpose, a brushing time of 10h (=72,000
      strokes) is needed. In further comparative studies, specimens of different
      materials should be tested in one series to estimate the true variability.

PMID- 20036419
TI  - Honeybee silk: recombinant protein production, assembly and fiber spinning.
AB  - Transgenic production of silkworm and spider silks as biomaterials has posed
      intrinsic problems due to the large size and repetitive nature of the silk
      proteins. In contrast the silk of honeybees (Apis mellifera) is composed of a
      family of four small and non-repetitive fibrous proteins. We report recombinant
      production and purification of the four full-length unmodified honeybee silk
      proteins in Escherichia coli at substantial yields of 0.2-2.5 g/L. Under the
      correct conditions the recombinant proteins self-assembled to reproduce the
      native coiled coil structure. Using a simple biomimetic spinning system we could
      fabricate recombinant silk fibers that replicated the tensile strength of the
      native material.

PMID- 20036420
TI  - Lactose mediated liver-targeting effect observed by ex vivo imaging technology.
AB  - Two kinds of micelles containing Rhodamine B were prepared by a solvent
      evaporation method. One (Lac-f-micelles: lactose-free micelles) was from a
      Rhodamine-containing copolymer, poly(ethylene glycol)-b-poly(l-lactide-co-2,2
      dihydroxylmethyl-propylene carbonate/Rhodamine) [PEG(5000)-b-P(LA(4000)-co
      DHP(600)/Rhodamine)], and the other (Lac+micelles lactose-containing micelles)
      was from a mixture of the targeting copolymer lactose-poly(ethylene glycol)-poly
      (l-Lactide) [Lac-PEG(4600)-PLA(4500)] and the Rhodamine-containing copolymer
      PEG(5000)-b-P(LA(4000)-co-DHP(600)/Rhodamine). ESEM and DLS measurements showed
      that the two kinds of micelles have similar size (in the range of 60-100 nm) and
      size distribution. Cellular uptake studies in vitro revealed that the
      Lac+micelles showed stronger endocytosis ability than Lac-f-micelles in SMMC7221
      human liver cancer cells, but the Lac+micelles were rarely internalized by Vero
      cells. The micelle solutions were administrated into mice via tail intravenous
      injection. Then, five visceral organs were isolated from the mice at specified
      time intervals and relative fluorescent intensities of the ex vivo organs and
      their homogenates were examined by CRI Maestro 500FL in vivo imaging system. The
      results showed that the Lac+micelles showed more remarkable liver-targeting
      effect than the Lac-f-micelles. And the liver-targeting effect could be
      established in ca. 12 h after tail i.v. injection.

PMID- 20036422
TI  - Detection of circulating lymphoma cells in patients with non-Hodgkin lymphoma
      using MAGE-A3 gene expression in peripheral blood.
AB  - BACKGROUND/AIMS: Lymphoma-specific gene expression in peripheral blood reflects
      the presence of circulating lymphoma cells (CLCs). MAGE-A3 is widely expressed in
      solid tumors and is a potent candidate for immunotherapy. To determine whether
      MAGE-A3 expression would be a useful marker for CLCs in non-Hodgkin lymphoma
      (NHL), we assessed MAGE-A3 mRNA expression in the peripheral blood of NHL
      patients and controls. METHODS: We measured MAGE-A3 gene expression in ten
      lymphoma cell lines (Farage, RL, SU-DHL, Toledo, WSU-NHL, BJA-B, Daudi, Raji,
      Granta-519 and Jurkat) using nested RT-PCR, and determined detection sensitivity
      using mixtures of MAGE-A3-positive and -negative cells over a range of 1/10(6) to
      10(6)/10(6) cells. MAGE-A3 expression was determined in buffy coat samples of 40
      controls and 95 NHL patients prior to treatment. Clinical characteristics (e.g.,
      cell lineage) and international prognostic indices, including age, performance,
      LDH, stage and extra-nodal involvement, were evaluated and related to MAGE-A3
      expression. Hazard ratios, reflecting risk for overall survival and progression
      free survival, were also evaluated. Follow-up MAGE-A3 expression was evaluated at
      two time points: after 3-4 cycles of chemotherapy (80 patients) and after 6-8
      cycles of chemotherapy (74 patients). RESULTS: MAGE-A3 mRNA was detected in four
      lymphoma cell lines - RL, Farage, Toledo and Raji - and was present in 45 of 95
      (47.3%) patients with NHL, but in none of the 40 controls. The detection
      sensitivity was 1 in 1000 cells. MAGE-A3 expression prior to treatment was not
      associated with clinical features or patient survival. During follow-up, only six
      patients (7.5%) were positive for MAGE-A3 after 3-4 cycles of chemotherapy and
      three (4.1%) were positive after 6-8 cycles. CONCLUSIONS: The results showed that
      MAGE-A3 gene expression was frequent in NHL patients and decreased after
      effective chemotherapy, suggesting that MAGE-A3 can be used as a tumor marker for
      CLCs in patients with NHL. However, MAGE-A3 expression showed no prognostic value
      in this group of patients.

PMID- 20036421
TI  - The effects of TGF-alpha, IL-1beta and PDGF on fibroblast adhesion to ECM-derived
      matrix and KGF gene expression.
AB  - The goal of this study was to elucidate the control mechanisms by which exogenous
      proteins regulate keratinocyte growth factor (KGF) expression in fibroblasts
      adhered to differing substrates and thereby provide insights into both
      fundamental in vitro cell signaling and cell-biomaterial interaction research. A
      serum-free culture system in which cells maintained their proliferative capacity
      was established and employed. The addition of transforming growth factor- alpha
      (TGF-alpha), interleukin-1beta (IL-1beta) and platelet-derived growth factor-BB
      (PDGF-BB) individually showed no effect on KGF protein release, however, IL-1beta
      addition led to increased KGF mRNA transcription, intracellular KGF protein
      synthesis, and granulocyte-macrophage colony-stimulating factor (GM-CSF) release.
      Intracellular KGF protein synthesis and extracellular release were enhanced when
      fibroblasts were treated with a combination of IL-1beta and PDGF-BB which
      suggests KGF synthesis and release are largely regulated by synergistic
      mechanisms. Surface-bound fibronectin-derived ligands and individual exogenous
      proteins promoted fibroblast adhesion to semi-interpenetrating polymer networks
      (sIPNs) but did not stimulate KGF release despite enhancement of KGF mRNA
      transcription. Additionally, serum conditioning was found to have a significant
      impact on KGF synthesis and the subsequent mechanisms controlling KGF release.
      This study demonstrates that KGF release from fibroblasts is likely regulated by
      multiple mechanisms involving post-transcriptional and exocytic controls which
      may be impacted by the presence of serum and how serum is removed from the in
      vitro cell environment.

PMID- 20036423
TI  - Psidium guajava as a bioaccumulator of nickel around an oil refinery, southern
      Brazil.
AB  - To evaluate the potential of Psidium guajava as a biological accumulator of air
      pollutants, saplings were exposed at nine sites receiving atmospheric emissions
      from an oil refinery (five within, four outside the industrial area) and another
      reference site located at the Federal University of Rio Grande do Sul, 27 km from
      the refinery. Exposures lasted about 3 months each, coincided with the seasons,
      and totaled five exposures between 2005 and 2006. The following parameters were
      evaluated: dry weight of leaves, stems, and roots, leaf area, rate of relative
      height increase, Ni and S contents, maximum assimilation rate, and carboxylation
      efficiency invivo. P. guajava was found to be an efficient accumulator of Ni,
      since highly significant differences were observed (P<0.001) between sites within
      the industrial area and the reference site for all periods of exposure and a
      significant negative correlation between distance from emission source and Ni
      content. The S content showed significant differences (P<0.05) only at sites
      within the industrial area for two exposures. The dry weight, leaf area, rate of
      relative height increase, maximum assimilation rate, and carboxylation efficiency
      did not present significant differences for any period of exposure. In view of
      the above, we conclude that P. guajava is a good bioaccumulator for Ni.

PMID- 20036424
TI  - Selecting tolerant grass seedlings and analyzing the possibility for using aged
      refuse as sward soil.
AB  - In order to test the possibility for recycling use of aged refuse as sward soil,
      the study determined the responses of Lolium perenne L. (perennial ryegrass),
      Festuca arundinacea (tall fescue), and Poa annua (annual bluegrass) to its
      leaching. The growth of three seedlings was significantly inhibited after
      treatment, especially for longer treatment duration and higher concentration
      leaching; however, with the better growth and chlorophyll content for shorter
      time and lower concentration, tall fescue was more tolerant to the stress.
      Afterwards, several physiological responses of tall fescue were determined. For
      shorter treatment duration, antioxidant enzyme activities remained unchanged, and
      no obvious oxidative damage was observed. Prolonging exposure time, lipid
      peroxidation and protein oxidation occurred after treatment of higher
      concentration leaching, accompanying by changes of antioxidant status. It
      implicates that it is possible for using aged refuse as sward soil, and the
      critical point focused on selecting tolerant grass and controlling exposure
      condition.

PMID- 20036425
TI  - UV-vis and FT-IR spectra of ultraviolet irradiated collagen in the presence of
      antioxidant ascorbic acid.
AB  - The influence of deleterious UV radiation on collagen molecules in the absence
      and presence of ascorbic acid using UV-vis and FT-IR spectroscopy has been
      studied. Intensity of UV-vis absorption spectrum of collagen with a maximum at
      275 m due to the aromatic residues (tyrosine and phenylalanine) increases with
      the increasing dose of UV radiation. This effect is significantly hindered in the
      presence of antioxidant ascorbic acid. Intensities of FT-IR bands (amide A, B, I
      and II) of collagen decrease with the increase of the UV radiation dosage.
      Intensities of bands are also decreased in the presence of ascorbic acid. Results
      suggest that increasing the concentration of ascorbic acid increases the photo
      stability of collagen, and the collagen becomes less sensitive to UV radiation.
      It is possible that hydrogen bonds form between the groups N-H of collagen and
      C=O of ascorbic acid. It is believed that under UV radiation free radicals appear
      in acid soluble collagen and resulting in photodegradation of the macromolecule
      restore due to the ability of ascorbic acid donating one or two electrons.
      Increasing the dose of radiation causes more molecules of ascorbic acid to slow
      down, and their antioxidant effect is diminished accordingly.

PMID- 20036426
TI  - Binding and hydrolysis studies of antitumoural titanocene dichloride and
      Titanocene Y with phosphate diesters.
AB  - The interaction of the antitumoural metallocene dihalides, titanocene dichloride
      (Cp(2)TiCl(2)) and Titanocene Y (bis-[(p
      methoxybenzyl)cyclopentadienyl]titanium(IV) chloride), with bis(4-nitrophenyl)
      phosphate (BNPP), which is a widely used model for the phosphate diester linkages
      in DNA, has been studied. Cp(2)TiCl(2) has been shown to promote the cleavage of
      the phosphate diester in weakly acidic solution. At pH 4, 37 degrees C, a 10(6)
      fold rate acceleration over the uncatalysed reaction was observed under pseudo
      first-order conditions, when freshly prepared solutions of Cp(2)TiCl(2) were
      applied. The activity of aged solutions dropped significantly due to the
      formation of insoluble precipitates of hydrolysed Ti species. The precipitates
      isolated from aged solutions were shown to act as moderately active,
      heterogeneous catalysts for BNPP cleavage. By contrast, no hydrolysis of the
      phosphate diester could be observed in the presence of Titanocene Y. Implications
      for the mode of action of the apoptosis-inducing metallocene dihalides are
      discussed.

PMID- 20036427
TI  - Double-blind comparison of 30 and 60 mg tranylcypromine daily in patients with
      panic disorder comorbid with social anxiety disorder.
AB  - Our objective was to explore the dose-response relationship in patients with
      panic disorder and social anxiety disorder comorbidity (DSM-IV). After 1 week of
      no-drug washout, 36 such patients were assigned to a double-blind controlled
      comparison of the effects of 30 mg and 60 mg of tranylcypromine, and were
      followed up for 12 weeks. The main instrument used to measure the number of panic
      attacks was the Sheehan Panic and Anticipatory Anxiety Scale. The primary outcome
      measure for social anxiety disorder symptoms was the mean change from baseline in
      the Liebowitz Social Anxiety Scale (LSAS). After 12 weeks of treatment, panic
      attacks were reduced 69.6% from baseline in the 30-mg group (n=19) compared with
      a 74.8% reduction in the 60-mg group (n=17). Twelve patients (70.6%) of the
      higher dose group and 14 patients (68.4%) of the lower dose were completely free
      of panic attacks. There was no difference in efficacy between the tranylcypromine
      groups in the panic disorder symptoms. The 60-mg dose was more efficacious as
      measured by the LSAS scores, showing a significant difference in relation to the
      lower group. Mean change from baseline in LSAS total score (mean+/-SD) for 30-mg
      group was 17.9+/-14.7 and for the 60-mg group was 35.0+/-14.8. The social anxiety
      symptom scale showed a two-fold greater change with the 60-mg dose, and the 30-mg
      dose group could be considered the equivalent of a placebo control group.
      Tranylcypromine--60 mg daily--was found effective in the treatment of panic
      disorder and social anxiety disorder comorbidity.

PMID- 20036428
TI  - Epidemiological analysis of microtia: a retrospective study in 345 patients in
      China.
AB  - OBJECTIVE: To study the epidemiologic characteristics of microtia in China and to
      investigate the possible risk factors with respect to the classification of
      microtia. METHODS: A total of 345 patients with microtia were studied. All
      patients were taken an intentional physical examination and classified into five
      types. A detailed questionnaire concerning the maternal conditions during
      pregnancy was filled out by patient's mother. The frequencies of the relative
      factors were counted and the variables were statistically analyzed using Chi
      Square and Fisher's tests in the five types of microtia. RESULTS: Most cases of
      microtia (88.12%) were sporadic and 72.75% of all cases occurred in males. It was
      more seen unilateral, especially affected on the right side (55.94%). A total of
      195 patients (56.52%) were isolated microtia. In the rest of non-isolated
      microtia patients, 37.97% of the cases had hemifacial microsomia, which was the
      most common associated deformity. Thirty-four patients (9.86%) belonged to
      typical familial microtia. Three maternal factors showed significant differences
      in the five types of microtia, which were perinatal virus infection, high prior
      miscarriages and prevention treatments for threatened abortion. CONCLUSIONS: The
      majority of microtia cases in China are sporadic and usually more common in
      males. Mothers who have prior miscarriages over 3 times or perinatal virus
      infection seem to be more likely to have severe microtia infants.

PMID- 20036430
TI  - ST-segment changes after direct current external cardioversion for atrial
      fibrillation. Incidence, characteristics and predictive factors.
AB  - BACKGROUND: Incidence, characteristics and predictive factors of transient ST
      segment changes after DC shock are poorly known. METHODS: 91 consecutive pts
      referred for external cardioversion of atrial fibrillation (AF) (61 men, 69+/-10
      yo) were prospectively included. The presence of ST elevation or depression was
      assessed on 12 lead-ECG immediately after the first DC shock. Correlations with
      DC shock characteristics (monophasic/biphasic and energy), clinical variables,
      echocardiographic parameters, biological parameters, medications, anaesthetic
      drugs as well with morphological features were made. RESULTS: 18 and 20 pts
      underwent 200 J or 300 J monophasic and 53 pts 200 J biphasic DC shocks. We found
      an incidence of 48% for ST-segment changes: 35% for ST elevation and 13% for ST
      depression. ST changes did not induce significant cardiac events or alter AF
      recurrences. ST changes were not related to energy but ST elevation was
      significantly more often induced by monophasic (76% vs 6%, p<0.0001) and ST
      depression by biphasic DC shocks (26% vs 3%, p=0.01). Using multivariate
      analysis, independent predictors for ST elevation were the use of monophasic DC
      shocks, of propofol and increased CRP, while a low ejection fraction and use of
      biphasic DC shocks were independent predictors of ST depression. CONCLUSION: ST
      segment changes after external cardioversion with DC shock are common, short
      living and do not carry clinical significance. They are related to the monophasic
      or biphasic configuration of DC shock, to the use of propofol, to the ejection
      fraction and to an increased CRP.

PMID- 20036429
TI  - Pharmacological facilitation of fear extinction and the search for adjunct
      treatments for anxiety disorders--the case of yohimbine.
AB  - There is current interest in identifying drugs that facilitate fear extinction,
      as this form of learning is the basis of certain cognitive therapies for anxiety
      disorders. Following an initial report several years ago that the alpha2
      adrenoreceptor antagonist yohimbine facilitated extinction in mice, more recent
      studies have shown mixed effects or even impairment. It has become clear that the
      effect of yohimbine on extinction depends on a number of factors, including
      genetic background, contextual variables and the presence of competing behaviors.
      To what extent theses effects of yohimbine are mediated through the alpha2
      adrenoreceptor, as opposed to other sites of action, is also uncertain. More work
      is needed before this drug can be approved as a pharmacological adjunct for
      extinction-based therapies. More generally, the case of yohimbine may serve as a
      model for the development of other extinction facilitators.

PMID- 20036431
TI  - Tolerance and HIV.
AB  - We empirically investigate the effect of tolerance for gays on the spread of HIV
      in the United States. Using a state-level panel dataset spanning the mid-1970s to
      the mid-1990s, we find that tolerance is negatively associated with the HIV rate.
      We then investigate the causal mechanisms potentially underlying this
      relationship. We find evidence consistent with the theory that tolerance for
      homosexuals causes low-risk men to enter the pool of homosexual partners, as well
      as causes sexually active men to substitute away from underground, anonymous, and
      risky behaviors, both of which lower the HIV rate.

PMID- 20036432
TI  - Glycolytic metabolism and tumour response to fractionated irradiation.
AB  - BACKGROUND AND PURPOSE: To study whether pre-therapeutic lactate or pyruvate
      predict for tumour response to fractionated irradiation and to identify possible
      coherencies between intermediates of glycolysis and expression levels of selected
      proteins. MATERIALS AND METHODS: Concentrations of lactate, pyruvate, glucose and
      ATP were quantified via bioluminescence imaging in tumour xenografts derived from
      10 human head and neck squamous cell carcinoma (HNSCC) lines. Tumours were
      irradiated with 30 fractions within 6 weeks. Expression levels of the selected
      proteins in tumours were measured at the mRNA and protein level. Tumour
      infiltrating leucocytes were quantified after staining for CD45. RESULTS: Lactate
      but not pyruvate concentrations were significantly correlated with tumour
      response to fractionated irradiation. Lactate concentrations in vivo did not
      reflect lactate production rates in vitro. Metabolite concentrations did not
      correlate with GLUT1, PFK-L or LDH-A at the transcriptional or protein level.
      CD45-positive cell infiltration was low in the majority of tumours and did not
      correlate with lactate concentration. CONCLUSIONS: Our data support the
      hypothesis that the antioxidative capacity of lactate may contribute to
      radioresistance in malignant tumours. Non-invasive imaging of lactate to monitor
      radiation response and testing inhibitors of glycolysis to improve outcome after
      fractionated radiotherapy warrant further investigations.

PMID- 20036433
TI  - Patient-reported tolerability issues with oral antidiabetic agents: Associations
      with adherence; treatment satisfaction and health-related quality of life.
AB  - AIMS: The study's aim was to quantify prevalence of tolerability issues among
      patients with T2DM currently treated with OADs and to assess its association with
      treatment adherence, satisfaction and health-related quality of life (HRQL).
      METHODS: Data were collected from the 2006-2008 US National Health and Wellness
      Survey and the Ailment Panel of Lightspeed Online Research, an internet-based
      questionnaire. Participants (N=2074) self-reported a diagnosis of T2DM, were >18
      years of age and currently taking >1 OADs but not insulin, and spoke English.
      RESULTS: The majority (71.7%) experienced at least 1 tolerability issue in the
      past 2 weeks; 49.7% experienced >2. Tolerability issues included signs/symptoms
      of hypoglycemia (57.2%), constipation/diarrhea (28%), headaches (25.6%), weight
      gain (22.9%) and water retention (21.0%). There was a significant association
      between the number of tolerability issues and both the likelihood of non
      adherence (r=0.20, p<0.01) and reduced treatment satisfaction (r=-0.42, p<0.01).
      Each additional tolerability issue was associated with 28% greater likelihood of
      medication non-adherence. Constipation/diarrhea (b=-0.02, p<0.01) and symptoms of
      hypoglycemia (b=-0.08, p<0.01) were significantly associated with lower HRQL
      scores. CONCLUSIONS: Optimizing OAD therapy of T2DM by improving tolerability may
      increase patient satisfaction, medication adherence and HRQL, and may increase
      the likelihood of attaining treatment goals.

PMID- 20036434
TI  - Establishment of a Community Advisory Board (CAB) for tuberculosis control and
      research in the Inanda, Ntuzuma and KwaMashu (INK) area of KwaZulu-Natal, South
      Africa.
AB  - OBJECTIVES: To strengthen community mobilization, education, awareness and
      involvement in research to improve Tuberculosis (TB) control, by building
      partnership between communities and the health sector through the establishment
      of a Community Advisory Board (CAB) in the Inanda, Ntuzuma and KwaMashu (INK)
      area. METHODS: Key stakeholders from multiple sectors of the target community
      were identified. Two workshops were held with the aim of communicating the need
      for CAB and selecting its members. A 22 member INK CAB with representatives from
      different sectors in the community was selected. CAB members were trained through
      a 2-day workshop on TB and research. RESULTS: Various activities were
      successfully initiated and spearheaded by the INK CAB, and these involved
      training of Traditional Healers, recruiting of more TB tracer teams, organizing
      awareness campaigns during TB World Day, establishing TB school peer educators
      and links with NGOs to support impoverished TB patients all with positive
      outcomes. CONCLUSIONS: The INK CAB is a successful example of providing a
      mechanism for community consultation and participation that contributes to
      promoting and facilitating relevant research and TB control activities.

PMID- 20036435
TI  - The US Orphan Drug Act: rare disease research stimulator or commercial
      opportunity?
AB  - OBJECTIVES: This study investigates issues associated with the United States
      Orphan Drug Act. METHODS: A comprehensive orphan drug database was compiled from
      FDA data and corporate annual reports of major pharmaceutical companies. Analysis
      allowed the generation of a descriptive orphan drug portrait as well as
      documentation of orphan drugs along their lifecycle. RESULTS: Currently, 2002
      products have obtained orphan drug designation with 352 drugs obtaining FDA
      approval. Approximately 33% of orphan drugs are oncology products. On average,
      products obtain 1.7 orphan designations with approximately 70% obtaining a single
      designation. At least 9% of orphan drugs have reached blockbuster status with two
      thirds having two or more designations. An additional 25 orphan drugs had sales
      exceeding US$ 100 million in 2008 alone. Since 1983, at least 14 previously
      discontinued products have been recycled as orphan drugs. CONCLUSIONS: The United
      States Orphan Drug Act has created issues which, in some cases, have led to
      commercial and ethical abuses. Orphan Drug Act reform is necessary but current
      incentives, including 7 year market exclusivity, should be maintained in order to
      favour patients as well as economic prosperity. Suggested reforms include price
      regulation, subsidy paybacks for profitable drugs and the establishment of an
      International Orphan Drug Office.

PMID- 20036436
TI  - Tandem repeat polymorphisms: modulators of disease susceptibility and candidates
      for 'missing heritability'.
AB  - A problem of 'missing heritability' has been identified following recent genome
      wide association (GWA) studies of single nucleotide polymorphisms (SNPs)
      associated with complex diseases. Current GWA studies fail to detect key sources
      of genetic variation, particularly tandem-repeat polymorphisms (TRPs), which
      provide a unique source of genetic variability by modulating a range of
      biological processes. Expanded tandem repeats cause various monogenic disorders,
      including Huntington's disease and various ataxias. However, there is emerging
      evidence suggesting that TRPs have a role in polygenic diseases. For example,
      candidate gene studies have found associations between specific TRPs and various
      brain disorders. Future GWA studies that include all TRPs as genetic variables
      will reveal the full extent of their association with complex diseases. TRPs
      might provide substantial genetic variability contributing to complex polygenic
      diseases and could be an important source of the missing heritability evident in
      SNP-based GWA studies.

PMID- 20036437
TI  - Two chaperonin systems in bacterial genomes with distinct ecological roles.
AB  - Bacterial chaperonins are essential to cell viability and have a role in
      endosymbiosis, which leads to increased biological complexity. However, the
      extent to which chaperonins promote ecological innovation is unknown. We screened
      622 bacterial genomes for genes encoding chaperonins, and found archaeal-like
      chaperonins in bacteria that inhabit archaeal ecological niches. We found that
      chaperonins encoded in pathogenic bacteria are the most functionally divergent.
      We identified the molecular basis of the dramatic structural changes in
      mitochondrial GROEL, a highly derived chaperonin gene. Our analysis suggests that
      chaperonins are important capacitors of evolutionary and ecological change.

PMID- 20036438
TI  - Computer-aided vestibular autorotational testing of the vestibulo-ocular reflex
      in senile vestibular dysfunction.
AB  - BACKGROUND AND OBJECTIVE: Studies have already investigated vestibulo-ocular
      reflex (VOR) responses in elderly subjects, mostly at low frequencies (<1 Hz)
      during passive head turns, or continuous active head turns in a rotational chair.
      However, natural head movements usually occur at frequencies above 1 Hz and at
      varying rates, rather than at continuously increasing rates as tested in most
      studies to date. The aim of this study was to compare VOR responses within or
      between normal and bilateral peripheral vestibular hypofunction (BPVH) elderly
      subjects with a computer base program incorporating random active high-frequency
      head movements. SUBJECTS: Seventeen senior patients with bilateral peripheral
      vestibular hypofunction and 13 age-matched paid healthy subjects participated in
      this study. DESIGN: All the subjects performed 8s of active, side-to-side head
      motions at 1 Hz, 2 Hz and 3 Hz in response to four experimental conditions: (A) a
      stationary visual target; (B) a stationary visual target and a moving target with
      a horizontal trajectory; (C) a stationary visual target and a moving target with
      a spiral trajectory; and (D) a stationary visual target with combined horizontal-
      and vertical-spiral moving targets. RESULTS: Repeated-measures ANOVA showed that
      across the different frequencies of headshaking, a significant increase took
      place in the phase lag of the BPVH subjects (p<0.001) compared with the normal
      controls. Post hoc analysis showed significant within-group differences in BPVH
      subjects (1 Hz vs 2 Hz, 2 Hz vs 3 Hz) and normal controls (1 Hz vs 2 Hz, 1 Hz vs
      3 Hz). A significant VOR gain took place among the BPVH subjects at 3 Hz VAT
      (p<0.001) as compared with 1 Hz VAT and no significant differences in VOR gain
      could be detected among the controls at either of these frequencies. Repeated
      measures ANOVA revealed that under our test conditions, significant main effect
      was noted for VOR asymmetry (F=4.45, p<0.05). Post hoc analysis showed
      significant within-group differences in the BPVH subjects (test A vs test B, test
      A vs test C, and test A vs test D). CONCLUSIONS: Our results showed that the VAT
      paradigm can be improved by using concurrent horizontal and vertical moving
      targets. The VOR phase may be useful for differentiating VAT responses between
      BPVH and healthy elderly subjects. Moreover, the results of this study
      demonstrate that gains in VOR at different frequencies of headshaking and
      asymmetry during different test conditions can be useful parameters for within
      group assessment.

PMID- 20036439
TI  - A novel method for pediatric heart sound segmentation without using the ECG.
AB  - In this paper, we propose a novel method for pediatric heart sounds segmentation
      by paying special attention to the physiological effects of respiration on
      pediatric heart sounds. The segmentation is accomplished in three steps. First,
      the envelope of a heart sounds signal is obtained with emphasis on the first
      heart sound (S(1)) and the second heart sound (S(2)) by using short time spectral
      energy and autoregressive (AR) parameters of the signal. Then, the basic heart
      sounds are extracted taking into account the repetitive and spectral
      characteristics of S(1) and S(2) sounds by using a Multi-Layer Perceptron (MLP)
      neural network classifier. In the final step, by considering the diastolic and
      systolic intervals variations due to the effect of a child's respiration, a
      complete and precise heart sounds end-pointing and segmentation is achieved.

PMID- 20036441
TI  - Role of the GNOM gene in Arabidopsis apical-basal patterning--From mutant
      phenotype to cellular mechanism of protein action.
AB  - How the apical-basal axis of polarity is established in embryogenesis is still a
      mystery in plant development. This axis appeared specifically compromised by
      mutations in the Arabidopsis GNOM gene. Surprisingly, GNOM encodes an ARF guanine
      nucleotide exchange factor (ARF-GEF) that regulates the formation of vesicles in
      membrane trafficking. In-depth functional analysis of GNOM and its closest
      relative, GNOM-LIKE 1 (GNL1), has provided a mechanistic explanation for the
      development-specific role of a seemingly mundane trafficking regulator. The
      current model proposes that GNOM is specifically involved in the endosomal
      recycling of the auxin-efflux carrier PIN1 to the basal plasma membrane in
      provascular cells, which in turn is required for the accumulation of the plant
      hormone auxin at the future root pole through polar auxin transport. Thus, the
      analysis of GNOM highlights the importance of cell-biological processes for a
      mechanistic understanding of development.

PMID- 20036440
TI  - VeriStrat classifier for survival and time to progression in non-small cell lung
      cancer (NSCLC) patients treated with erlotinib and bevacizumab.
AB  - We applied an established and commercially available serum proteomic classifier
      for survival after treatment with erlotinib (VeriStrat) in a blinded manner to
      pretreatment sera obtained from recurrent advanced NSCLC patients before
      treatment with the combination of erlotinib plus bevacizumab. We found that
      VeriStrat could classify these patients into two groups with significantly better
      or worse outcomes and may enable rational selection of patients more likely to
      benefit from this costly and potentially toxic regimen.

PMID- 20036442
TI  - Sucrose accumulation in watermelon fruits: genetic variation and biochemical
      analysis.
AB  - Sugar accumulation, the key process determining fruit quality, is controlled by
      both the translocation of sugars and their metabolism in developing fruits. Sugar
      composition in watermelon, as in all cucurbit fruits, includes sucrose, fructose
      and glucose. The proportions of these three sugars are determined primarily by
      three enzyme families: invertases, sucrose synthases (SuSys) and sucrose
      phosphate synthases (SPSs). The goal of the present research was to explore the
      process of sugar metabolism in watermelon fruits. Crosses between the domestic
      watermelon (Citrullus lanatus) and three wild species provided a wide germplasm
      to explore genetic variability in sugar composition and metabolism. This survey
      demonstrated great genetic variability in sugar content and in the proportions of
      sucrose, glucose and fructose in mature fruits. Genotypes accumulating high and
      low percentage of sucrose provided an experimental system to study sugar
      metabolism in developing fruits. Insoluble invertase activity was high and
      constant throughout fruit development in control lines and in genotypes
      accumulating low levels of sucrose, while in genotypes accumulating high levels
      of sucrose, activity declined sharply 4 weeks after pollination. Soluble acid
      invertase activity was significantly lower in genotypes accumulating high levels
      of sucrose than in low-sucrose-accumulating genotypes. Conversely, activities of
      SuSy and SPS were higher in the high-sucrose-accumulating genotypes. The present
      results establish that, within the genus Citrullus, there are genotypes that
      accumulate a high percentage of sucrose in the fruit, while others accumulate
      high percentages of glucose and fructose. The significant negative correlation
      between insoluble invertase activity and fruit sucrose level suggests that
      sucrose accumulation is affected by both phloem unloading and sugar metabolism.

PMID- 20036443
TI  - Health care workers' views about respirator use and features that should be
      included in the next generation of respirators.
AB  - BACKGROUND: Numerous studies have demonstrated that health care workers are, in
      general, poorly compliant with respiratory protection guidelines, especially when
      a N95 respirator is recommended. The purpose of this study was to assess health
      care workers' views about respirator use and the features they prefer to be
      included in the next generation of respirators. METHODS: A 63-item survey was
      distributed to health care workers in 27 units of 2 tertiary care medical
      centers. RESULTS: From a total of 559 surveys distributed at both hospitals, 159
      responses were returned (response rate, 28%). Survey results indicated that
      health care workers seek respirators that are more comfortable, interfere less
      with breathing, diminish heat buildup, are disposable, and permit the user to
      have facial hair. Multivariate analyses suggest that emergency department staff
      had 12.3 greater odds of wanting a new respirator (P = .031) as compared with
      their referent group. Males were more likely to indicate that the N95 respirator
      was comfortable to wear versus females (P = .003). CONCLUSION: To increase
      substantially the acceptance of respiratory protective equipment and improve
      compliance rates, respirators should be modified to meet the specific needs of
      health care workers.

PMID- 20036444
TI  - Metabotropic glutamate receptor type 5 in levodopa-induced motor complications.
AB  - Metabotropic glutamate receptors type 5 (mGluR5) are implicated in regulation of
      synaptic plasticity and learning, and were the focus of our investigation in
      human Parkinson's disease (PD) patients with dyskinesias and wearing-off, and in
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys with dyskinesias.
      Using the selective mGluR5 ligand [(3)H]ABP688 autoradiography, we measured
      mGluR5 in brain slices from 11 normal and 14 PD patients and from MPTP monkeys,
      in relation to motor complications (dyskinesias and wearing-off) associated with
      treatment with l-dopa. In 16 monkeys with a bilateral MPTP lesion and four
      controls, [(3)H]ABP688 specific binding was elevated in the striatum of
      dyskinetic l-dopa-treated MPTP monkeys but not in MPTP monkeys without
      dyskinesias compared to controls. PD patients with motor complications (either
      dyskinesias or wearing-off) had higher [(3)H]ABP688 specific binding compared to
      those without motor complications and controls in putamen, external and internal
      globus pallidus. Elevated glutamatergic transmission as measured with increased
      mGluR5 specific binding was associated with motor complications and its
      antagonism could be targeted for their treatment.

PMID- 20036445
TI  - Structure of aldehyde reductase in ternary complex with a 5-arylidene-2,4
      thiazolidinedione aldose reductase inhibitor.
AB  - The structure of aldehyde reductase (ALR1) in ternary complex with the coenzyme
      NADPH and [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3
      yl]acetic acid (CMD), a potent inhibitor of aldose reductase (ALR2), was
      determined at 1.99A resolution. The partially disordered inhibitor formed a tight
      network of hydrogen bonds with the active site residues (Tyr50 and His113) and
      coenzyme. Molecular modelling calculations and inhibitory activity measurements
      of CMD and [5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic
      acid (HMD) indicated that pi-stacking interactions with several conserved active
      site tryptophan residues and hydrogen-bonding interactions with the non-conserved
      C-terminal residue Leu300 in ALR2 (Pro301 in ALR1) contributed to inhibitor
      selectivity. In particular for the potent inhibitor CMD, the rotameric state of
      the conserved residue Trp219 (Trp220 in ALR1) is important in forming a pi
      stacking interaction with the inhibitor in ALR2 and contributes to the difference
      in the binding of the inhibitor to the enzymes.

PMID- 20036446
TI  - Synthesis and investigation of inhibition effect of fluorinated sulfonamide
      derivatives on carbonic anhydrase.
AB  - Series of perfluoroalkanesulfonamides 1, sodium salt of
      perfluoroalkanesulfonamides 2 and polyfluoroalkanesulfonamides 3 derivatives were
      synthesized and characterized by (1)H NMR, (13)C NMR, (19)F NMR, IR and HRMS.
      Inhibition effects of these compounds on bovine carbonic anhydrase (bCA) and
      human carbonic anhydrase isoenzyme II (hCA) have been investigated. Comparing
      IC(50) values of the synthesized molecules 1, 2 and 3, it has been found that
      compound 2b is a more potent inhibitor than acetazolamide on hCA. Moreover 2b
      does not present cellular toxicity on sheep red globules.

PMID- 20036447
TI  - Antioxidant and antiviral activities of silybin fatty acid conjugates.
AB  - Two selective acylation methods for silybin esterification with long-chain fatty
      acids were developed, yielding a series of silybin 7-O- and 23-O-acyl-derivatives
      of varying acyl chain lengths. These compounds were tested for their antioxidant
      (inhibition of lipid peroxidation and DPPH-scavenging) and anti-influenza virus
      activities. The acyl chain length is an important prerequisite for both
      biological activities, as they improved with increasing length of the acyl
      moiety.

PMID- 20036448
TI  - Synthesis of potent BACE-1 inhibitors incorporating a hydroxyethylene isostere as
      central core.
AB  - We herein describe the design and synthesis of a series of BACE-1 inhibitors
      incorporating a P1-substituted hydroxylethylene transition state isostere. The
      synthetic route starting from commercially available carbohydrates yielded a
      pivotal lactone intermediate with excellent stereochemical control which
      subsequently could be diversified at the P1-position. The final inhibitors were
      optimized using three different amines to provide the residues in the P2'-P3'
      position and three different acids affording the residues in the P2-P3 position.
      In addition we report on the stereochemical preference of the P1'-methyl
      substituent in the synthesized inhibitors. All inhibitors were evaluated in an in
      vitro BACE-1 assay where the most potent inhibitor, 34-(R), exhibited a BACE-1
      IC(50) value of 3.1 nM.

PMID- 20036450
TI  - Accumulation and biological cycling of heavy metal in four salt marsh species,
      from Tagus estuary (Portugal).
AB  - Pools of Zn, Cu, Cd and Co in leaf, stem and root tissues of Sarcocornia
      fruticosa, Sarcocornia perennis, Halimione portulacoides and Spartina maritima
      were analyzed on a bimonthly basis, in a Tagus estuary salt marsh. All the major
      concentrations were found in the root tissues, being the concentrations in the
      aboveground organs neglectable for sediment budget proposes, as seen by the low
      root-aboveground translocation. Metal annual accumulation, root turnovers and
      cycling coefficients were also assessed. S. maritima showed the higher root
      turnovers and cycling coefficients for most of the analyzed metals, making this a
      phytostabilizer specie. By contrast the low root turnover, cycling coefficient
      and low root necromass generation makes S. perennis the most suitable specie for
      phytoremediation processes. Although the high amounts of metal return to the
      sediments, due to root senescence, salt marshes can still be considered sinks of
      heavy metals, cycling heavy metals mostly between sediment and root.

PMID- 20036449
TI  - Advances of air pollution science: from forest decline to multiple-stress effects
      on forest ecosystem services.
AB  - Over the past 20 years, the focus of forest science on air pollution has moved
      from forest decline to a holistic framework of forest health, and from the
      effects on forest production to the ecosystem services provided by forest
      ecosystems. Hence, future research should focus on the interacting factorial
      impacts and resulting antagonistic and synergistic responses of forest trees and
      ecosystems. The synergistic effects of air pollution and climatic changes, in
      particular elevated ozone, altered nitrogen, carbon and water availability, must
      be key issues for research. Present evidence suggests air pollution will become
      increasingly harmful to forests under climate change, which requires integration
      amongst various stressors (abiotic and biotic factors, including competition,
      parasites and fire), effects on forest services (production, biodiversity
      protection, soil protection, sustained water balance, socio-economical relevance)
      and assessment approaches (research, monitoring, modeling) to be fostered.

PMID- 20036451
TI  - Spatially distributed pesticide exposure assessment in the Central Valley,
      California, USA.
AB  - Field runoff is an important transport mechanism by which pesticides move into
      the hydrologic environment of intensive agricultural regions such as California's
      Central Valley. This study presents a spatially explicit modeling approach to
      extend Pesticide Root Zone Model (PRZM), a field-scale pesticide transport model,
      into basin level. The approach was applied to simulate chlorpyrifos use in the
      Central Valley during 2003-2007. The average value of loading as percent of use
      (LAPU) is 0.031%. Results of this study provide strong evidence that surface
      runoff generation and pesticide application timing are the two influencing
      factors on the spatial and temporal variability of chlorpyrifos sources from
      agricultural fields. This is one of the first studies in coupling GIS and field
      scale models and providing simulations for the dynamics of pesticides over an
      agriculturally dominated landscape. The demonstrated modeling approach may be
      useful for implementations of best management practice (BMP) and total maximum
      daily load (TMDL).

PMID- 20036452
TI  - How do land-based salmonid farms affect stream ecology?
AB  - Increasing research is highlighting the fact that streams provide crucial
      ecosystem services through the biogeochemical and ecological processes they
      sustain. Freshwater land-based salmonid farms commonly discharge their effluents
      into low order, headwater streams, partly due to the fact that adequate
      freshwater resources for production are commonly found in undisturbed areas. We
      review the effects of salmonid farm effluents on different biological components
      of stream ecosystems. Relevant considerations related to the temporal and spatial
      scales of effluent discharge and ecological effects are discussed. These
      highlight the need to characterize the patterns of stressor discharge when
      assessing environmental impacts and designing ecological effects studies. The
      potential role of multiple stressors in disrupting ecosystem structure and
      function is discussed with an emphasis on aquaculture veterinary medicines.
      Further research on the effects of veterinary medicines using relevant exposure
      scenarios would significantly contribute to our understanding of their impact in
      relation to other effluent stressors.

PMID- 20036453
TI  - Interactions between plant and rhizosphere microbial communities in a
      metalliferous soil.
AB  - In the present work, the relationships between plant consortia, consisting of 1-4
      metallicolous pseudometallophytes with different metal-tolerance strategies
      (Thlaspi caerulescens: hyperaccumulator; Jasione montana: accumulator; Rumex
      acetosa: indicator; Festuca rubra: excluder), and their rhizosphere microbial
      communities were studied in a mine soil polluted with high levels of Cd, Pb and
      Zn. Physiological response and phytoremediation potential of the studied
      pseudometallophytes were also investigated. The studied metallicolous populations
      are tolerant to metal pollution and offer potential for the development of
      phytoextraction and phytostabilization technologies. T. caerulescens appears very
      tolerant to metal stress and most suitable for metal phytoextraction; the other
      three species enhance soil functionality. Soil microbial properties had a
      stronger effect on plant biomass rather than the other way around (35.2% versus
      14.9%). An ecological understanding of how contaminants, ecosystem functions and
      biological communities interact in the long-term is needed for proper management
      of these fragile metalliferous ecosystems.

PMID- 20036454
TI  - The value of symptoms and signs in the emergent diagnosis of acute coronary
      syndromes.
AB  - OBJECTIVE: Patient history and physical examination are widely accepted as
      cornerstones of diagnosis in modern medicine. We aimed to assess the value of
      individual historical and examination findings for diagnosing acute myocardial
      infarction (AMI) and predicting adverse cardiac events in undifferentiated
      Emergency Department (ED) patients with chest pain. METHODS: We prospectively
      recruited patients presenting to the ED with suspected cardiac chest pain.
      Clinical features were recorded using a custom-designed report form. All patients
      were followed up for the diagnosis of AMI and the occurrence of adverse events
      (death, AMI or urgent revascularization) within 6 months. RESULTS: AMI was
      diagnosed in 148 (18.6%) of the 796 patients recruited. Following adjustment for
      age, sex and ECG changes, the following characteristics made AMI more likely
      (adjusted odds ratio, 95% confidence intervals): pain radiating to the right arm
      (2.23, 1.24-4.00), both arms (2.69, 1.36-5.36), vomiting (3.50, 1.81-6.77),
      central chest pain (3.29, 1.94-5.61) and sweating observed (5.18, 3.02-8.86).
      Pain in the left anterior chest made AMI significantly less likely (0.25, 0.14
      0.46). The presence of rest pain (0.67, 0.41-1.10) or pain radiating to the left
      arm (1.36, 0.89-2.09) did not significantly alter the probability of AMI.
      CONCLUSIONS: Our results challenge many widely held assertions about the value of
      individual symptoms and signs in ED patients with suspected acute coronary
      syndromes. Several 'atypical' symptoms actually render AMI more likely, whereas
      many 'typical' symptoms that are often considered to identify high-risk
      populations have no diagnostic value.

PMID- 20036455
TI  - Torsades de pointes in amitraz poisoning.

PMID- 20036456
TI  - Using 100% oxygen for the resuscitation of term neonates until evidence of
      spontaneous circulation: more investigations needed.

PMID- 20036457
TI  - Intraventricular bleeding and transient hydrocephalus in a patient with
      hemorrhagic filum terminale ependymoma undergoing anticoagulation therapy with
      phenprocoumon.
AB  - The authors discuss a rare case of hemorrhage in a filum terminale ependymoma
      presenting with acute paraparesis and transient hydrocephalic dementia in
      association with long-term phenprocoumon anticoagulation. The CT scan of the
      brain revealed the presence of blood in both occipital horns and communicating
      hydrocephalus. The symptoms gradually resolved after tumor removal and there was
      no need for shunting. This is a complex clinical presentation of a spinal cord
      tumor associated hemorrhage, which further illustrates the possibility of
      retrograde passage of blood from the lumbosacral region to the ventricles.

PMID- 20036458
TI  - Primary CNS hemangiopericytoma presenting as an intraparenchymal mass--case
      report and review of literature.
AB  - Hemangiopericytomas (HPC) are rare, aggressive tumours that mostly involve the
      musculoskeletal system. They account for less than 1% of intracranial tumours.
      Intracranially, they are predominantly meningeal based and are thought to arise
      from the spindle cells (pericytes) in the vicinity of the blood vessels. We
      present a case of a 69-year-old male with a hemangiopericytoma in the left
      perisylvian region which was subcortically located. This is an uncommon location.
      We discuss the case and review the literature.

PMID- 20036459
TI  - Human papillomavirus and p16 expression in inverted papillomas of the urinary
      bladder.
AB  - Human Papillomaviruses (HPVs) have been found in association with benign and
      malignant growth of epithelia. The cell cycle inhibitor p16(Ink4a) has been shown
      to be overexpressed in HPV-positive cervical pre-malignant and malignant lesions,
      probably as a result of pRB targeting by the viral E7 protein. Inverted
      papillomas of the urinary bladder are epithelial tumors considered to be of
      benign nature. In this report we analyze the expression of p16(Ink4a) and the
      presence of HPV sequences in inverted papillomas and in non-tumoral bladder
      controls. Our results show no association of HPV infection and inverted
      papillomas. Further, no correlation between p16 overexpression and HPV positivity
      was found. We conclude that HPV does not play an indispensable role in the
      development of urinary bladder inverted papillomas and that overexpression of
      p16(Ink4a) does not correlate with HPV infection in these tumors.

PMID- 20036460
TI  - Biosorption of lead using immobilized Aeromonas hydrophila biomass in up flow
      column system: factorial design for process optimization.
AB  - Free and immobilized biomass of Aeromonas hydrophila has been utilized for the
      removal of Pb(II) from aqueous solution. Fitness of Langmuir sorption model to
      the sorption data indicated the sorption was monolayer and uptake capacity of
      biomass was 163.9 and 138.88 mg/g for the free and immobilized biomass
      respectively. 85.38% Pb(II) removal was achieved at bed height of 19 cm and flow
      rate of 2 mL/min and BDST model was in a good agreement with the experimental
      results (r(2)>0.997). An attempt has been made to optimize the process conditions
      for the maximum removal using Central Composite Design with the help of Minitab
      15 software and the result predicted by optimization plots was 88.27% which is
      close to the experimental data i.e. 85.38%. Sorption-desorption studies revealed
      that polysulfone immobilized biomass could reused up to 16 cycles and bed was
      completely exhaust after 33 cycles.

PMID- 20036461
TI  - Laccase production by Aspergillus heteromorphus using distillery spent wash and
      lignocellulosic biomass.
AB  - Laccase is among the major enzymes which plays an important role in ligninolytic
      system of fungi. Laccase production by Aspergillus heteromorphus was studied
      using anaerobically treated distillery spent wash (ADSW) and lignocellulosic
      biomass. Lignocellulosic biomass (rice straw, wheat straw and sugarcane bagasse)
      generated during biomass processing leads to solid waste and distillery spent
      wash is unwanted liquid waste produced by distilleries, both causes environmental
      pollution. Two mineral media and anaerobically treated distillery spent wash
      medium was tested for laccase production. Enzyme production in various media and
      in presence and absence of lignocellulosic biomass supplements showed that
      anaerobically treated distillery spent wash medium was a better laccase inducer
      medium than the mineral media. Addition of lignocellulosic biomass enhances
      laccase production and highest laccase activity was obtained in 5% anaerobically
      treated distillery spent wash medium with rice straw.

PMID- 20036462
TI  - A probabilistic approach to quantitatively assess the inhalation risk for
      airborne endotoxin in cotton textile workers.
AB  - Endotoxin, a component of gram-negative bacterial cell walls, is a
      proinflammatory agent that induces local and systemic inflammatory responses in
      normal subjects which can contribute to the risk of developing asthma and chronic
      obstructive lung diseases. A probabilistic approach linking models of exposure,
      internal dosimetry, and health effects were carried out to quantitatively assess
      the potential inhalation risk of airborne endotoxin for workers in cotton textile
      plants. Combining empirical data and modeling results, we show that the half
      maximum effects of the endotoxin dose (ED50) were estimated to be 3.3 x 10(5)
      (95% confidence interval (CI): 1.9-14.7 x 10(5)) endotoxin units (EU) for the
      blood C-reactive protein (CRP) concentration, 1.1 x 10(5) (95% CI: 0.6-1.7 x
      10(5))EU for the blood polymorphonuclear neutrophil (PMN) count, and 1.5 x 10(5)
      (95% CI: 0.4-2.5 x 10(5))EU for the sputum PMN count. Our study offers a risk
      management framework for discussing future establishment of limits for
      respiratory exposure to airborne endotoxin for workers in cotton textile plants.

PMID- 20036463
TI  - Adsorption of cadmium (II) ions from aqueous solution by a new low-cost adsorbent
      -bamboo charcoal.
AB  - Batch adsorption experiments were conducted for the adsorption of Cd (II) ions
      from aqueous solution by bamboo charcoal. The results showed that the adsorption
      of Cd (II) ions was very fast initially and the equilibrium time was 6h. High pH
      (>or=8.0) was favorable for the adsorption and removal of Cd (II) ions. Higher
      initial Cd concentrations led to lower removal percentages but higher adsorption
      capacity. As the adsorbent dose increased, the removal of Cd increased, while the
      adsorption capacity decreased. Adsorption kinetics of Cd (II) ions onto bamboo
      charcoal could be best described by the pseudo-second-order model. The adsorption
      behavior of Cd (II) ions fitted Langmuir, Temkin and Freundlich isotherms well,
      but followed Langmuir isotherm most precisely, with a maximum adsorption capacity
      of 12.08 mg/g. EDS analysis confirmed that Cd (II) was adsorbed onto bamboo
      charcoal. This study demonstrated that bamboo charcoal could be used for the
      removal of Cd (II) ions in water treatment.

PMID- 20036464
TI  - Image deformation in field ion microscopy of faceted crystals.
AB  - We perform detailed numerical simulations of field ion microscopy images of
      faceted crystals and compare them with experimental observations. In contrast to
      the case of crystals with a smooth surface, for a faceted topography we find
      extreme deformations of the ion image. Local magnification is highly
      inhomogeneous and may vary by an order of magnitude: from 0.64 to 6.7. Moreover,
      the anisotropy of the magnification at a point located on the facet edge may
      reach a factor of 10.

PMID- 20036465
TI  - Air conditioning in Burns Units.

PMID- 20036467
TI  - How dangerous are phthalate plasticizers? Integrated approach to toxicity based
      on metabolism, electron transfer, reactive oxygen species and cell signaling.
AB  - Phthalate plasticizers are the most abundant man-made pollutants that have
      recently received wide-spread attention. There is uncertainty concerning the
      toxicity to humans. During the debate, scant attention has been paid to adverse
      effects at the molecular level which is the focus of this article. Most metabolic
      reports are concerned only with ester hydrolysis. In addition to that aspect, an
      important study deals with formation of catechol carboxylic acids which have the
      potential to redox cycle with the o-quinone counterparts. This electron transfer
      (ET) process is capable of generating reactive oxygen species (ROS) which are
      well known toxic agents at elevated levels. Substantial numbers of investigations
      find the presence of ROS leading to oxidative stress (OS) in living systems
      containing phthalates. Insults occur to various organs, including the
      reproductive system, pulmonary, central nervous system, immune system and liver.
      Toxic reactions are also reported involving inflammation, mitochondria and
      carcinogenicity. Generally, OS evidently plays a role. Of relevance are prior
      reviews which document extensive evidence for association of ET-ROS-OS with organ
      toxicity, and other deleterious reactions. In addition, cell signaling has been
      related to the physiological effects of phthalates. Various signaling processes
      participate together with involvement of ROS and association with biological
      effects. Suggestions for future work are offered.

PMID- 20036466
TI  - Fear potentiation is associated with hypothalamic-pituitary-adrenal axis function
      in PTSD.
AB  - A central problem in posttraumatic stress disorder (PTSD) is the inability to
      suppress fear under safe conditions. We have previously shown that PTSD patients
      cannot inhibit conditioned fear. Another relevant finding in PTSD is the
      hypersensitivity of the hypothalamic-pituitary-adrenal (HPA) axis feedback. Given
      their common neurobiological pathways, alterations in HPA function in PTSD may be
      associated with impaired fear inhibition. The present study examined the
      relationship between HPA axis function and fear-potentiated startle and
      inhibition of conditioned fear in trauma-exposed individuals. We used a
      conditional discrimination procedure (AX+/BX-), in which one set of shapes (AX+)
      was paired with aversive airblasts to the throat (danger signal), and the same X
      shape with a different shape (BX-) were presented without airblasts (safety
      signal). The paradigm also included a transfer of fear inhibition test (AB). In
      addition to fear-potentiated startle, blood was drawn for neuroendocrine analysis
      and the dexamethasone suppression test (DEX) was performed; cortisol and ACTH
      were assessed at baseline and post-DEX. Ninety highly traumatized individuals
      recruited from Grady Hospital in Atlanta, GA participated in the study. The
      sample was divided into those who met DSM-IV criteria for PTSD (n=29) and Non
      PTSD controls (n=61) using the PTSD symptom scale (PSS). Both groups showed
      significant reduction in cortisol and ACTH levels after DEX. Subjects with PTSD
      had higher fear-potentiated startle to the safety signal, BX- (F(1,88)=4.44,
      p<0.05) and fear inhibition trials, AB (F(1,88)=5.20, p<0.05), both indicative of
      less fear inhibition in the presence of B, compared to control subjects. In
      addition, fear-potentiated startle to AX+, BX-, and AB was positively correlated
      with baseline and post-DEX ACTH in PTSD subjects. These results suggest that
      impaired fear inhibition and associated alterations in HPA feedback may reflect
      amygdala hyperactivity in subjects with PTSD.

PMID- 20036468
TI  - [Is there still any interest of x-ray pelvimetry for women with a scarred
      uterus].
AB  - OBJECTIVES: To revalue the interest of X-ray pelvimetry and analyse our current
      management of patients with a previous caesarean delivery. PATIENTS AND METHODS:
      Case-control retrospective study reviewing 418 case records of women with a
      scarred uterus: a study group of 206 parturients who delivered in 2002, when X
      ray pelvimetry was the rule, compared with a control group of 212 parturients who
      delivered in 2007, without any X-ray pelvimetry. Outcomes of labour, influence of
      X-ray pelvimetry, indications of caesarean sections, rates of uterine rupture and
      neonatal well-being have been analysed. RESULTS: There was no significant
      difference between both groups concerning the outcomes of labour. The transverse
      pelvic diameter is positively correlated with an eutocic delivery and inversely
      correlated with the rate of caesarean section performed during labour because of
      obstructed labour. Measurements of the pelvis were unrelated neither to the risk
      of uterine rupture nor to the neonatal outcome. The risk of uterine rupture is
      significantly higher when an emergency caesarean section is required. CONCLUSION:
      Our study brings to light a complementary point of view about X-ray pelvimetry.
      Indeed, our results show that it could be useful in the following of a caesarean
      section for obstructed labour.

PMID- 20036469
TI  - Isolation and identification of yeast flora from genital tract in healthy female
      camels (Camelus dromedarius).
AB  - Yeasts are commensal organisms found in the skin, genital and gastrointestinal
      tracts, and other mucosal sites in mammalians. The purposes of this study were to
      identify yeast flora and to determine the number of colony forming units (CFUs)
      in genital tract of healthy female dromedary camels, establishing their
      connection in both mated and unmated conditions. The samples were taken from
      different parts of genital tract including vestibule, vagina, cervix, uterine
      body, and uterine horns of 50 camels using sterilized cotton swabs. They were
      cultured onto Sabouraud glucose agar containing chloramphenicol and incubated at
      30 degrees C for 7-10 days. A total of 454 yeast colonies were obtained from
      genital tract. Yeast isolates belonged to 8 genera: Candida (73.1%), Trichosporon
      (10.1%), Geotrichum (7.5%), Kluyveromyces (3.5%), Rhodotorula (2.4%),
      Aureobasidium (1.4%), Cryptococcus (1.1%) and Prototheca (0.8%). Among different
      Candida species, C. zeylanoides was the most common isolated species,
      representing significant difference with other Candida species (P<0.05). The mean
      number of yeasts found in the vestibule (46%) was significantly higher than the
      results obtained from other parts (P<0.05). In addition, the mean value of CFUs
      from unmated females (71.1%) was significantly higher than mated females
      (P<0.05). The results showed that C. zeylanoides was a common component of
      healthy camel females' genital mycoflora and the number of yeasts varied between
      mated and unmated females.

PMID- 20036470
TI  - Detection and management of oncology drug interactions: Can we do better?

PMID- 20036471
TI  - Comparative analysis of the uterine and mammary gland effects of progesterone and
      medroxyprogesterone acetate.
AB  - OBJECTIVES: In combined hormone replacement therapy (HRT) progestins are used to
      inhibit estradiol-activated uterine epithelial cell proliferation. In comparison
      to estradiol-only therapy, combined HRT leads to enhanced proliferation of
      mammary epithelial cells. In a quantitative mouse model, we assessed the balance
      between uterine and undesired mammary gland effects for two progestins that are
      widely used in HRT, progesterone and medroxyprogesterone acetate. STUDY DESIGN:
      Mice were ovariectomized and after 14 days they were treated subcutaneously with
      either vehicle, estradiol (100 ng) or estradiol plus increasing doses of
      progesterone or medroxyprogesterone acetate for three weeks. MAIN OUTCOME
      MEASURES: Measures for progestogenic mammary gland activity were stimulation of
      side-branching and stimulation of epithelial cell proliferation. Progestogenic
      activity in the uterus was assessed by measuring inhibition of estradiol
      activated uterine epithelial cell proliferation. ED(50) and ID(50) values for the
      distinct readouts were obtained and dissociation factors for uterine versus
      mammary gland activity were calculated. RESULTS: MPA demonstrated uterine
      activity and mitogenic activity in the mammary gland at the same doses. In
      contrast, progesterone showed uterine activity at doses lower than those leading
      to significant stimulation of epithelial cell proliferation in the mammary gland.
      CONCLUSIONS: Progestins do not behave the same. Use of the natural hormone
      progesterone, but not MPA, in combined hormone therapy might offer a safety
      window between uterine effects and undesired proliferative activity in the
      mammary gland.

PMID- 20036472
TI  - Urine testing for norcodeine, norhydrocodone, and noroxycodone facilitates
      interpretation and reduces false negatives.
AB  - Urine drug testing of pain patients provides objective information to health
      specialists regarding patient compliance, diversion, and concurrent illicit drug
      use. Interpretation of urine test results for semi-synthetic opiates can be
      difficult because of complex biotransformations of parent drug to metabolites
      that are also available commercially and may be abused. Normetabolites such as
      norcodeine, norhydrocodone and noroxycodone are unique metabolites that are not
      available commercially. Consequently, detection of normetabolite in specimens not
      containing parent drug, provides conclusive evidence that the parent drug was
      consumed. The goal of this study was to evaluate the prevalence and patterns of
      the three normetabolites, norcodeine, norhydrocodone and noroxycodone, in urine
      specimens of pain patients treated with opiates. Urine specimens were hydrolyzed
      with beta-glucuronidase and analyzed by a validated liquid chromatography tandem
      mass spectrometry (LC/MS/MS) assay for the presence of codeine, norcodeine,
      morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone,
      noroxycodone, and oxymorphone. The limit of quantitation (LOQ) for these analytes
      was 50ng/mL. The study was approved by an Institutional Review Board. Of the
      total specimens (N=2654) tested, 71.4% (N=1895) were positive (>or=LOQ) for one
      or more of the analytes. The prevalence (%) of positive results for codeine,
      hydrocodone and oxycodone was 1.2%, 26.1%, and 36.2%, respectively, and the
      prevalence of norcodeine, norhydrocodone and noroxycodone was 0.5%, 22.1%, and
      31.3%, respectively. For specimens containing normetabolite, the prevalence of
      norcodeine, norhydrocodone and noroxycodone in the absence of parent drug was
      8.6%, 7.8% and 9.4%, respectively. From one-third to two-thirds of these
      specimens also did not contain other metabolites that could have originated from
      the parent drug. Consequently, the authors conclude that inclusion of norcodeine,
      norhydrocodone and noroxycodone is useful in interpretation of opiate drug source
      and reduces potential false negatives that would occur without tests for these
      unique metabolites.

PMID- 20036473
TI  - Intractable Meniere's disease. Modelling of the treatment by means of statistical
      analysis.
AB  - OBJECTIVE: To evaluate the value of different variables of the clinical history,
      auditory and vestibular tests and handicap measurements to define intractable or
      disabling Meniere's disease. METHODS: This is a prospective study with 212
      patients of which 155 were treated with intratympanic gentamicin and considered
      to be suffering a medically intractable Meniere's disease. Age and sex
      adjustments were performed with the 11 variables selected. Discriminant analysis
      was performed either using the aforementioned variables or following the stepwise
      method. RESULTS: Different variables needed to be sex and/or age adjusted and
      both data were included in the discriminant function. Two different mathematical
      formulas were obtained and four models were analyzed. With the model selected,
      diagnostic accuracy is 77.7%, sensitivity is 94.9% and specificity is 52.8%.
      CONCLUSION: After discriminant analysis we found that the most informative
      variables were the number of vertigo spells, the speech discrimination score, the
      time constant of the VOR and a measure of handicap, the "dizziness index".

PMID- 20036474
TI  - Percutaneous chemical myotomy using botulium neurtoxin A under local anaesthesia
      in the treatment of cricopharyngeal dysphagia following laryngectomy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the outcome of the use of
      percutaneous injection of botulinum neurotoxin A under local anaesthesia in the
      management of cricophayngeus dysphagia in post-laryngectomy patients. METHODS:
      Fifteen post-laryngectomy patients (6 males, 9 females, age range 48-72 years)
      with surgery performed not less than five years with post-operative radiotherapy
      were recruited. Under video-fluoroscopic control and the attachment of a metal
      safety pin to the neck as a topographical marker for the cricopharyngeus muscle,
      botulinum neurotoxin was injected after local anaesthesia infiltration. Patients
      were followed up for a 4 months period with repeated video-fluoroscopy and
      telephone self-assessment and weight change. RESULTS: Eighty seven percent of
      patients noticed some improvement in their dysphagia. One patient reported an
      adverse reaction of pain at the site of injection. CONCLUSION: Percutaneous local
      injection of botulinum neurotoxin A is a simple, safe and cost-effective means of
      improving cricopharyngeal dysphagia in post-laryngectomy patients when general
      anaesthesia is contra-indicated.

PMID- 20036475
TI  - A novel permanent tracheostomy technique for prevention of stomal stenosis
      (triangular tracheostomy).
AB  - OBJECTIVE: Stenosis of a permanent tracheostoma after total laryngectomy lowers
      postoperative quality of life (QOL), and its prevention is clinically important.
      METHODS: From April 2003 to March 2009, the authors performed 87 permanent
      tracheostomies. For the purpose of prevention of tracheostomal stenosis, we had
      applied new technique from October 2005. RESULTS: The incidence of the
      tracheostomal stenosis was retrospectively reviewed. Until September 2005,
      conventional permanent tracheostomy was applied for 33 cases and tracheostomal
      stenosis developed in 6 cases (18.2%). On the other hand, stenosis did not
      develop in any of the 54 cases in which the new technique was used. The
      triangular method was significantly superior to the conventional method in
      preventing stenosis. Stomal recurrence did not develop in either technique.
      CONCLUSION: The key point of the new technique is as follows: at the upper end of
      trachea, the posterior part of tracheal cartilage is preserved and the anterior
      edge of the tracheostoma is made much lower. The shape of the tracheostoma
      approximates a triangle, and the area is greater than with other methods. From
      our experience, this technique is safe and effective for the prevention of
      tracheostomal stenosis.

PMID- 20036476
TI  - [Case report: a complex anal fistula].

PMID- 20036477
TI  - High-throughput determination of faropenem in human plasma and urine by on-line
      solid-phase extraction coupled to high-performance liquid chromatography with UV
      detection and its application to the pharmacokinetic study.
AB  - An automated system using on-line solid-phase extraction and HPLC with UV
      detection was developed for the determination of faropenem in human plasma and
      urine. Analytical process was performed isocratically with two reversed-phase
      columns connected by a switching valve. After simple pretreatment for plasma and
      urine with acetonitrile, a volume of 100microl upper layer of the plasma or urine
      samples was injected for on-line SPE column switching HPLC-UV analysis. The
      analytes were retained on the self-made trap column (Lichrospher C(18),
      4.6mmx37mm, 25microm) with the loading solvent (20mM NaH(2)PO(4) adjusted pH 3.5)
      at flow rate of 2mlmin(-1), and most matrix materials were removed from the
      column to waste. After 0.5min washing, the valve was switched to another position
      so that the target analytes could be eluted from trap column to analytical column
      in the back-flush mode by the mobile phase (acetonitrile-20mM NaH(2)PO(4)
      adjusted pH 3.5, 16:84, v/v) at flow rate of 1.5mlmin(-1), and then separated on
      the analytical column (Ultimate XB-C(18), 4.6mmx50mm, 5microm).The complete cycle
      of the on-line SPE preconcentration purification and HPLC separation of the
      analytes was 5min. Calibration curves with good linearities (r=0.9994 for plasma
      sample and r=0.9988 for urine sample) were obtained in the range 0.02-5microgml(
      1) in plasma and 0.05-10microg ml(-1) in urine for faropenem. The optimized
      method showed good performance in terms of specificity, linearity, detection and
      quantification limits, precision and accuracy. The method was successfully
      utilized to quantify faropenem in human plasma and urine to support the clinical
      pharmacokinetic studies.

PMID- 20036478
TI  - Matrix deactivation: A general approach to improve stability of unstable and
      reactive pharmaceutical genotoxic impurities for trace analysis.
AB  - Trace analysis of unstable and reactive pharmaceutical genotoxic impurities
      (GTIs) is a challenging task in pharmaceutical analysis. Many method issues such
      as insufficient sensitivity, poor precision, and unusual (too high/low) spiking
      recovery are often directly related to analytes' instability. We report herein a
      matrix deactivation approach that chemically stabilizes these analytes for
      analytical method development. In contrast to the conventional chemical
      derivatization approach where the analytes are transformed into stable detectable
      species, the matrix deactivation approach chemically deactivates the hypothetical
      reactive species in the sample matrix. The matrix deactivation approach was
      developed on the premise that the instability of certain analytes at trace level
      is caused by reactions between the analytes and low level reactive species in the
      sample matrix. Thus, quenching the reactivity of the reactive species would be a
      key to stabilizing the unstable and reactive analytes. For example, electrophilic
      alkylators could be destabilized by nucleophiles or bases through either
      nucleophilic substitution or elimination reactions. One way to mask those
      reactive species is via protonation by adding acids to the diluent.
      Alternatively, one can use nucleophile scavengers to deplete reactive unknown
      species in the sample matrix completely, in analogy to the use of antioxidants
      and metal chelators to prevent oxidation in the analysis of compounds liable to
      oxidation. This paper reports the application of the matrix deactivation to the
      analyses of unstable and reactive pharmaceutical genotoxic impurities. Some of
      the methods have been used to support development of manufacturing processes for
      drug substances and a recent regulatory filing.

PMID- 20036479
TI  - Rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method for the quantification of topically applied azithromycin in rabbit
      conjunctiva tissues.
AB  - A simple, rapid, sensitive and selective liquid chromatography-tandem mass
      spectrometry method was developed and validated for the quantification of
      azithromycin in rabbit conjunctiva tissues using roxithromycin as internal
      standard. Following a deproteinization procedure, the samples were eluted
      isocratically at a flow rate of 0.3mL/min utilizing a mobile phase containing of
      10mM ammonium acetate (adjusted pH to 5.2 with 0.1% acetic acid)-methanol (18:82,
      v/v) and a SHISEIDO CAPCELL PAK C(18) (3.0mmx75mm, 3microm). Azithromycin and its
      internal standard were measured by a triple-quadrupole mass spectrometer in the
      selected reaction monitoring (SRM) mode with precursor-to-product qualifier
      transition m/z 375 [M+2H](2+)-->591 and m/z 837 [M+H](+)-->679 respectively. The
      method demonstrated that good linearity ranged from 10 to 2000ng/mL with
      r=0.9998. The lower limit of quantification for azithromycin in conjunctiva
      tissues was 10ng/mL with good accuracy and precision. The intra- and inter-day
      precision (RSD) values were below 15% and accuracy (%) ranged from 90% to 110% at
      all QC levels. The method was applicable to ocular pharmacokinetic studies of
      azithromycin.

PMID- 20036480
TI  - The importance of teaching clinicians when and how to work with interpreters.
AB  - OBJECTIVE: To describe the importance of teaching clinicians when and how to
      overcome language barriers in clinical practice, provide an example of a
      curriculum for teaching on this topic, and outline the critical issues that must
      be addressed in this type of teaching. METHODS: We describe a 1.5h educational
      program for students in a large urban medical school as an example curriculum and
      how it impacted student responses on a 28-item questionnaire measuring their
      knowledge, attitudes and likelihood of future behaviour before and after the
      course. The course components are described and highlight the essential
      components that should be included in teaching about overcoming language barriers
      in clinical practice. RESULTS: There were significant improvments in knowledge,
      attitudes, and reported likelihood of future behaviors after the educational
      program. Recommendations for essetential curricular components are made.
      CONCLUSION: Teaching clinicians about language barriers in health care and how to
      overcome them should be essential to all clinical curricula. Brief educational
      interventions can meet this need and should include a core set of essential
      teaching points as outlined. PRACTICE IMPLICATIONS: Teaching clinicians when and
      how to overcome language barriers in health care will help to reduce the impact
      of this barrier, make clinicians and interpreters' jobs easier and more
      transparent, and improve patient care and satisfaction.

PMID- 20036481
TI  - Platelet-derived growth factor acts via both the Rho-kinase and p38 signaling
      enzymes to stimulate contraction in an in vitro model of equine wound healing.
AB  - Horses are more prone to complications in the wound healing process than other
      species, and problems such as chronic inflammation, delayed epithelialization,
      poor wound contraction, and exuberant granulation tissue are commonly seen,
      particularly in wounds on the distal limbs. In comparison, wounds of the oral
      mucosa heal rapidly in a scarless fashion with a high degree of wound
      contraction. The effect of platelet-derived growth factor BB (PDGF), insulin-like
      growth factor (IGF)-1, and transforming growth factor beta1 (TGFbeta1) on the
      contraction of a fibroblast-populated collagen matrix (FPCM) as a model of equine
      wound contraction was investigated using equine oral fibroblasts. The fibroblasts
      were embedded into floating FPCM and treated with PDGF, IGF-1, and TGFbeta1. The
      surface areas of the FPCM were determined daily for 5 d. Platelet-derived growth
      factor significantly stimulated the contraction of the FPCM at an optimal
      concentration of 10 ng/mL (P=0.025). Insulin-like growth factor-1 and TGFbeta1
      did not significantly affect the contraction of the FPCM relative to the control.
      To elucidate the mechanisms by which PDGF stimulated contraction of FPCM, the Rho
      kinase and p38 cell signaling pathways were blocked, resulting in a significant
      inhibition (P<0.001) of PDGF-stimulated contraction. Platelet-derived growth
      factor BB is a potent stimulator of fibroblast migration, and hence the FPCM
      contraction generated here is probably a result of its effects on cell migration.
      The results of the present experiment suggest that this effect is stimulated via
      both the Rho-kinase and p38 signaling pathways in equine oral fibroblasts.

PMID- 20036482
TI  - MicroRNA-25 functions in regulation of pigmentation by targeting the
      transcription factor MITF in Alpaca (Lama pacos) skin melanocytes.
AB  - Although the influence of endocrine factors is well established, the molecular
      and cellular mechanisms controlling coat color are not completely understood. A
      major mechanism for post-transcriptional regulation of gene expression is through
      the action of microRNAs (miRNAs), which anneal to the 3' untranslated region of
      mRNAs in a sequence-specific fashion and either block translation or promote
      transcript degradation. In this study, we investigated the expression of miRNAs
      in the skin of alpacas with brown vs white coat color using a microarray screen;
      identified potential mRNA targets for identified miRNAs among coat color genes;
      and subsequently determined the ability of a specific, differentially expressed
      miRNA (miR-25) to suppress expression of micropthalmia-associated transcription
      factor (MITF), a predicted miR-25 target gene that regulates genes linked to coat
      color. Expression of 10 different miRNA species in the skin of alpacas with brown
      vs white coat color was identified from microarray screens. Of the 10 alpaca skin
      miRNAs identified, predicted binding sites in the 3' untranslated region of RNAs
      encoding for known genes linked to coat color were primarily for miR-25, but
      sites were also identified for miR-129 and miR-377. Potential miR-25 binding
      sites were present in transcripts encoding for 11 coat color genes, including
      MITF. An inverse relationship between transcript abundance for MITF and miR-25
      was observed in skin samples collected from alpacas with white vs brown coat
      color. Furthermore, overexpression of miR-25 in cultured melanocytes reduced MITF
      mRNA and protein abundance and corresponding mRNA abundance for the MITF
      regulated enzymes tyrosinase and tyrosinase-related protein 1. Results support a
      novel functional role for miRNA-25 in the regulation of gene expression linked to
      coat color.

PMID- 20036483
TI  - Expression of leukemia inhibitory factor and leukemia inhibitory factor receptor
      in the canine pituitary gland and corticotrope adenomas.
AB  - Leukemia inhibitory factor (LIF) is a pleiotropic cytokine of the IL-6 family
      that activates the hypothalamic-pituitary-adrenal axis and promotes corticotrope
      cell differentiation during development. The aim of this study was to investigate
      the expression of LIF and its receptor (LIFR) in the canine pituitary gland and
      in corticotrope adenomas, and to perform a mutation analysis of LIFR. Using
      immunohistochemistry, immunofluorescence, and quantitative expression analysis,
      LIF and LIFR expression were studied in pituitary glands of control dogs and in
      specimens of corticotrope adenoma tissue collected through hypophysectomy in dogs
      with pituitary-dependent hypercortisolism (PDH, Cushing's disease). Using
      sequence analysis, cDNA was screened for mutations in the LIFR. In the control
      pituitary tissues and corticotrope adenomas, there was a low magnitude of LIF
      expression. The LIFR, however, was highly expressed and co-localized with ACTH(1
      24) expression. Cytoplasmatic immunoreactivity of LIFR was preserved in
      corticotrope adenomas and adjacent nontumorous cells of pars intermedia. No
      mutation was found on mutation analysis of the complete LIFR cDNA. Surprisingly,
      nuclear to perinuclear immunoreactivity for LIFR was present in nontumorous
      pituitary cells of the pars distalis in 10 of 12 tissue specimens from PDH dogs.
      These data show that LIFR is highly co-expressed with adrenocorticotropic hormone
      (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in the canine
      pituitary gland and in corticotrope adenomas. Nuclear immunoreactivity for LIFR
      in nontumorous cells of the pars distalis may indicate the presence of a
      corticotrope adenoma.

PMID- 20036484
TI  - Zebrafish fetal alcohol syndrome model: effects of ethanol are rescued by
      retinoic acid supplement.
AB  - This study was designed to develop a zebrafish experimental model to examine
      defects in retinoic acid (RA) signaling caused by embryonic ethanol exposure. RA
      deficiency may be a causative factor leading to a spectrum of birth defects
      classified as fetal alcohol spectrum disorder (FASD). Experimental support for
      this hypothesis using Xenopus showed that effects of treatment with ethanol could
      be partially rescued by adding retinoids during ethanol treatment. Previous
      studies show that treating zebrafish embryos during gastrulation and
      somitogenesis stages with a pathophysiological concentration of ethanol (100mM)
      produces effects that are characteristic features of FASD. We found that treating
      zebrafish embryos with RA at a low concentration (10(-9)M) and 100mM ethanol
      during gastrulation and somitogenesis stages significantly rescued a spectrum of
      defects produced by treating embryos with 100mM ethanol alone. The rescued
      phenotype that we observed was quantitatively more similar to embryos treated
      with 10(-9)M RA alone (RA toxicity) than to untreated or 100mM ethanol-treated
      embryos. RA rescued defects caused by 100mM ethanol treatment during gastrulation
      and somitogenesis stages that include early gastrulation cell movements (anterior
      posterior axis), craniofacial cartilage formation, and ear development.
      Morphological evidence also suggests that other characteristic features of FASD
      (e.g., neural axis patterning) are rescued by RA supplement.

PMID- 20036485
TI  - A neurodevelopmental framework for the development of interventions for children
      with fetal alcohol spectrum disorders.
AB  - Despite considerable data published on cognitive and behavioral disabilities in
      children with fetal alcohol spectrum disorders (FASD), relatively little
      information is available on behavioral or pharmacological interventions for
      alcohol-affected children. The main goals of this article, therefore, are to
      summarize published intervention studies of FASD and to present a
      neurodevelopmental framework, based on recent findings from a number of
      disciplines, for designing new therapies for alcohol-affected children. This
      framework assumes a neuroconstructionist view, which posits that reciprocal
      interactions between neural activity and the brain's hardware lead to the
      progressive formation of intra- and interregional neural connections. In this
      view, behavioral interventions can be conceptualized as a series of guided
      experiences that are designed to produce neural activation. Based on evidence
      from cognitive neuroscience, it is hypothesized that specific interventions
      targeting executive attention and self-regulation may produce greater
      generalizable results than those aimed at domain-specific skills in children with
      FASD. In view of reciprocal interactions between environmental effects and neural
      structures, the proposed framework suggests that the maximum effects of
      interventions can eventually be achieved by optimally combining behavioral
      methods and cognition-enhancing drugs.

PMID- 20036486
TI  - Implementation of a shared data repository and common data dictionary for fetal
      alcohol spectrum disorders research.
AB  - Many previous attempts by fetal alcohol spectrum disorders researchers to compare
      data across multiple prospective and retrospective human studies have failed
      because of both structural differences in the collected data and difficulty in
      coming to agreement on the precise meaning of the terminology used to describe
      the collected data. Although some groups of researchers have an established track
      record of successfully integrating data, attempts to integrate data more broadly
      among different groups of researchers have generally faltered. Lack of tools to
      help researchers share and integrate data has also hampered data analysis. This
      situation has delayed improving diagnosis, intervention, and treatment before and
      after birth. We worked with various researchers and research programs in the
      Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop
      a set of common data dictionaries to describe the data to be collected, including
      definitions of terms and specification of allowable values. The resulting data
      dictionaries were the basis for creating a central data repository (CI-FASD
      Central Repository) and software tools to input and query data. Data entry
      restrictions ensure that only data that conform to the data dictionaries reach
      the CI-FASD Central Repository. The result is an effective system for centralized
      and unified management of the data collected and analyzed by the initiative,
      including a secure, long-term data repository. CI-FASD researchers are able to
      integrate and analyze data of different types, using multiple methods, and
      collected from multiple populations, and data are retained for future reuse in a
      secure, robust repository.

PMID- 20036487
TI  - A 14-year retrospective maternal report of alcohol consumption in pregnancy
      predicts pregnancy and teen outcomes.
AB  - Detecting patterns of maternal drinking that place fetuses at risk for fetal
      alcohol spectrum disorders (FASDs) is critical to diagnosis, treatment, and
      prevention but is challenging because information on antenatal drinking collected
      during pregnancy is often insufficient or lacking. Although retrospective
      assessments have been considered less favored by many researchers due to presumed
      poor reliability, this perception may be inaccurate because of reduced maternal
      denial and/or distortion. The present study hypothesized that fetal alcohol
      exposure, as assessed retrospectively during child adolescence, would be related
      significantly to prior measures of maternal drinking and would predict alcohol
      related behavioral problems in teens better than antenatal measures of maternal
      alcohol consumption. Drinking was assessed during pregnancy, and retrospectively
      about the same pregnancy, at a 14-year follow-up in 288 African-American women
      using well-validated semistructured interviews. Regression analysis examined the
      predictive validity of both drinking assessments on pregnancy outcomes and on
      teacher-reported teen behavior outcomes. Retrospective maternal self-reported
      drinking assessed 14 years postpartum was significantly higher than antenatal
      reports of consumption. Retrospective report identified 10.8 times more women as
      risk drinkers (>= one drink per day) than the antenatal report. Antenatal and
      retrospective reports were moderately correlated and both were correlated with
      the Michigan Alcoholism Screening Test. Self-reported alcohol consumption during
      pregnancy based on retrospective report identified significantly more teens
      exposed prenatally to at-risk alcohol levels than antenatal, in-pregnancy
      reports. Retrospective report predicted more teen behavior problems (e.g.,
      attention problems and externalizing behaviors) than the antenatal report.
      Antenatal report predicted younger gestational age at birth and retrospective
      report predicted smaller birth size; neither predicted teen IQ. These results
      suggest that if only antenatal, in-pregnancy maternal report is used, then a
      substantial proportion of children exposed prenatally to risk levels of alcohol
      might be misclassified. The validity of retrospective assessment of prior
      drinking during pregnancy as a more effective indicator of prenatal exposure was
      established by predicting more behavioral problems in teens than antenatal
      report. Retrospective report can provide valid information about drinking during
      a prior pregnancy and may facilitate diagnosis and subsequent interventions by
      educators, social service personnel, and health-care providers, thereby reducing
      the life-long impact of FASDs.

PMID- 20036489
TI  - Combined open and endovascular treatment of thoracoabdominal aneurysms and
      secondary expanding aortic dissections: early and mid-term results from a single
      center series.
AB  - BACKGROUND: We present a review of our experience with combined surgical therapy
      with endovascular stent repair and conventional revascularization of the
      supraaortic and/or visceral/renal arteries (hybrid procedure) in the treatment of
      thoracoabdominal aortic aneurysms and dissections. METHODS: We followed 20
      patients (7 women, median age 58.3 years, age range 37-68 years) prospectively.
      Severe comorbidity was present in 7 patients, 13 patients had previous aortic
      surgery. The median diameter of the thoracoabdominal aneurysm was 74.4 mm
      (Crawford I, 1 patient; II, 11; III, 7; V, 1), and 13 patients had previous
      aortic surgery. After visceral and renal revascularization, three stent grafts
      were implanted on average. Follow-up examination was every 6 months. The median
      follow-up was 174.5 days (15-375 days). RESULTS: The 30-day mortality was 10% and
      the neurological complication rate was 10% with incomplete paraparesis in 2
      patients. Computed tomography scanning revealed six endoleaks in 5 patients (Type
      Ia, 3 patients; Ib, 1; II, 1; III, 1) and four visceral graft occlusions in 4
      patients (right renal artery, 2 patients; left renal artery, 2). Endoleaks (Ia,
      Ib, and III) were surgically revised. During follow-up, 3 patients died. The
      remaining patients recovered to full activity. A significant aneurysm shrinkage
      was found in 5 patients. Two patients developed secondary endoleaks. CONCLUSION:
      Our results show that hybrid procedure might be an alternative to conventional
      thoracoabdominal repair of the aorta, especially in high-risk patients.

PMID- 20036490
TI  - Acceptable risk but small benefit of endovascular aneurysm repair in
      nonagenarians.
AB  - BACKGROUND: We report the outcomes of a single-center experience with
      endovascular aneurysm repair (EVAR) in nonagenarians. METHODS: Via a
      retrospective medical records review, we identified all patients > or = 90 years
      old who underwent EVAR at a single university teaching hospital during a 5-year
      period (January 2004 to December 2008). Patients were evaluated for surgical risk
      factor profile, preoperative imaging, technical success, postoperative
      complications, length of hospital stay, and need for secondary intervention. In
      addition, mortality rates were evaluated at 30 days, 365 days, and 2 years.
      RESULTS: There were 18 nonagenarians (12 male, 67%) with a mean age of 91.2 years
      (range 90-95). Each patient averaged 3.5 risk factors, and the mean preoperative
      maximal aneurysm size was 68.3mm (range 50-105). Sixteen (89%) patients were
      treated on an elective basis, and two patients were emergently treated for
      aneurysm rupture, with one undergoing aortouni-iliac stenting with femoral
      femoral bypass. All other patients in the study had bifurcated stent grafts.
      There was 100% technical success with no need for open conversion. The mean
      length of hospital stay was 4.3 days with a mean intensive care unit stay of 0.6
      days. Systemic complications occurred in three patients (17%) including one death
      within 30 days. Secondary interventions were required in two patients (11%). One
      had endovascular treatment of a type I endoleak at 4 months, and a second patient
      underwent femoral-femoral bypass at 25 months for severe flow-limiting limb
      angulation. Mortality rates were 5.6% at 30 days, 41.2% at 365 days, and 58.3% at
      2 years. Mean survival of the 11 patients who expired beyond the first 30 days
      was 17.5 months (range 4-50). Of these, mean survival of the nine patients
      treated electively was 20.2 months (range 7-50). Mean survival of the six
      patients still alive is 25.6 months (range 8-65). CONCLUSION: EVAR is safe in
      nonagenarians despite their advanced age and significant surgical risk factor
      profile. The procedure can be performed with excellent technical success and a
      low rate of perioperative complications. However, mortality rates after 30 days
      are significant. The substantial long-term mortality raises the question of
      possible treatment futility in this unique population. While age should not be a
      contraindication for EVAR, recommendations for the procedure should be based on
      individual patient selection.

PMID- 20036488
TI  - Collaborative initiative on fetal alcohol spectrum disorders: methodology of
      clinical projects.
AB  - The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) was
      created in 2003 to further understanding of fetal alcohol spectrum disorders.
      Clinical and basic science projects collect data across multiple sites using
      standardized methodology. This article describes the methodology being used by
      the clinical projects that pertain to assessment of children and adolescents.
      Domains being addressed are dysmorphology, neurobehavior, 3-D facial imaging, and
      brain imaging.

PMID- 20036491
TI  - Mycotic splenic artery aneurysm secondary to Coxiella burnetii endocarditis.
AB  - Mycotic artery aneurysms are rare but potentially lethal vascular lesions due to
      their high risk of rupture. Bacterial endocarditis as well as trauma and
      inadequate immunity are predisposing factors. Surgery remains the treatment of
      choice, although alternative methods have been used. We report the first known
      case of a 6 cm mycotic splenic artery aneurysm proximal to the splenic hilum,
      secondary to bacterial endocarditis from Coxiella burnetii. Resection of the
      aneurysm, splenectomy, and distal pancreatectomy were performed. In all patients
      with culture-negative endocarditis and mycotic aneurysm, C. burnetii infection
      should be ruled out.

PMID- 20036492
TI  - Reinfusion of blood within aneurysm sac: a simple method of intraoperative blood
      conservation in elective abdominal aortic surgery.
AB  - Autologous blood conservation reduces postoperative morbidity and mortality. In
      elective abdominal aortic aneurysm repair, the blood within the aneurysm sac is
      generally neglected during surgery. We present a simple method of additional
      blood conservation in elective abdominal aortic surgery, which involves
      reinfusion of autologous blood within the aneurysm sac in the perioperative
      period.

PMID- 20036493
TI  - Mesothelioma and internal carotid artery occlusion: acute ischemic stroke and
      efficacy of emergency carotid thrombectomy.
AB  - We report the case of a 54-year-old man with acute stroke caused by left internal
      carotid artery (ICA) occlusion secondary to pleural mesothelioma, discovered
      later. The cranial computed tomography scan revealed a left hemisphere ischemic
      lesion. At neurological examination, the modified National Institutes of Health
      Stroke Scale (mNIHSS) score was 9. The carotid duplex scan (DS) showed a complete
      thrombotic occlusion of the left ICA. The patient underwent emergency carotid
      thrombectomy. The screening tests revealed thrombocytosis, hyperfibrinogenemia,
      increased C-reactive protein values, and multiple left pleural mesothelioma
      nodularity confirmed at the immunohistochemical investigation. After surgery, the
      patient's neurological symptoms improved, with an mNIHSS score of 3. At 30 and
      120 days, the DS follow-up showed regular patency of the ICA.

PMID- 20036494
TI  - Congenital external carotid artery aneurysm.
AB  - An 8-month-old child presented with a right pulsatile neck mass. The tumor's
      rapid increase in size and respiratory problems prompted image evaluation. An
      external carotid artery aneurysm was found, which was compressing other neck
      structures. The patient underwent aneurysm resection and ligation at its
      insertion on the common carotid artery. Recovery was uneventful and no further
      aneurysms on other arteries were found.

PMID- 20036495
TI  - Leiomyosarcoma of the inferior vena cava: case report and treatment of recurrence
      with repeat surgery.
AB  - Leiomyosarcoma of the inferior vena cava (IVC) is an extremely rare malignancy
      with poor prognosis due to late diagnosis. Surgical resection currently remains
      the best treatment; however, recurrence frequently occurs and the 5-year survival
      rate is only 31%. The aim of this study is to report a case of IVC leiomyosarcoma
      and treatment of recurrence with repeat surgery. A 36-year-old woman with a high
      grade leiomyosarcoma originating from the infrahepatic IVC underwent an en bloc
      excision of the tumor. Eleven months after the initial operation, two metastases
      to the omentum were observed. Since the patient showed no response to adjuvant
      chemotherapy (i.e., a combination of 5-fluorouracil and gemcitabine), repeat
      operations were used as the main treatment modality for recurrence. The median
      time to recurrence was 15 months (range 8-27). The middle and upper IVC segments
      were involved in the local recurrence, and metastatic lesions occurred in
      multiple sites including the stomach, omentum, mesentery, left liver, and pelvic
      cavity. Repeat operations to remove the recurrent and metastatic tumors led to a
      long-term (at least 7 years) survival, and the patient is still alive.
      Postoperative recoveries were uneventful. Neither complication related to the
      venous blood flow in the IVC nor renal impairment was noted. Our results suggest
      that in the setting of chemotherapy-refractory IVC leiomyosarcoma repeat surgery
      may be an alternative treatment for recurrence and improve survival time.

PMID- 20036496
TI  - Infection of an aortic stent graft with suprarenal fixation.
AB  - We report a case of an elderly man admitted with abdominal pain and fever, 5
      months after endovascular aortic aneurysm repair of a suspected inflammatory
      abdominal aortic aneurysm. He underwent successful explantation of an infected
      stent graft with suprarenal fixation following extra-anatomic revascularization.
      After a prolonged hospitalization, he was discharged on antibiotics and at follow
      up has returned to baseline activity level. Although explantation of an infected
      prosthesis following endovascular aortic aneurysm repair has been previously
      reported, our case prompted a review of the literature to evaluate mode of
      presentation, putative factors, and management decisions associated with reduced
      morbidity and mortality.

PMID- 20036498
TI  - The effectiveness and feasibility of endovascular coil embolization for very
      small cerebral aneurysms: mid- and long-term follow-up.
AB  - BACKGROUND: Endovascular embolization for very small cerebral aneurysms (VSCAs)
      is still controversial. We report our experience with endovascular coil
      embolization for these lesions and assess the feasibility and effectiveness.
      METHODS: We conducted a review of our experience with endovascular treatment of a
      series of 19 patients with 20 VSCAs, located at the supraclinoid segment of the
      internal cranial artery (ICA) in seven, the cavernous ICA segment in three, the
      anterior communicating artery in five, vertebral artery-posterior inferior
      cerebellar artery in two, bifurcation of the middle cerebral artery in one, the
      pericallosal artery in one, and the P2 segment in one. The World Federation of
      Neurosurgical Societies classification before treatment was grade I in 14
      patients and grade II in five patients. The strategy of endovascular treatment
      included coil occlusion, balloon-assisted coiling, and stent-assisted coiling.
      Occlusion rate was divided into (1) total/near total, occlusion rate 95-100%; (2)
      subtotal, occlusion rate 80-95%; and (3) partial, occlusion rate<80%. Clinical
      outcome of patients with ruptured aneurysm was ascertained according to the
      Glasgow Outcomes Scale. RESULTS: All patients were successfully treated with coil
      embolization; immediate angiography determined occlusion of the aneurysm,
      including total occlusion in five, subtotal occlusion in nine, and partial
      occlusion in six. During 1-2 years of follow-up, all aneurysms were confirmed as
      complete occlusion by control angiography. No recurrence or coil compaction
      occurred. No rehemorrhage or ischemic stroke occurred. CONCLUSION: Endovascular
      coil embolization for VSCAs is effective and feasible. Initial subtotal or
      partial aneurysm occlusion might progress to total occlusion.

PMID- 20036497
TI  - Surgically implantable magnetic resonance angiography coils improve resolution to
      allow visualization of blood flow dynamics.
AB  - BACKGROUND: Magnetic resonance angiography (MRA) is clinically useful but of
      limited applicability to small animal models due to poor signal resolution, with
      typical voxel sizes of 1 mm(3) that are insufficient to analyze vessels of
      diameter <1 mm. We determined whether surgically implantable, extravascular MRA
      coils increase signal resolution adequately to examine blood flow dynamics
      METHODS: A custom MRA coil was surgically implanted near the carotid artery of a
      New Zealand White rabbit. A stenosis was created in the carotid artery to induce
      complicated, non-laminar flow. Phase contrast images were obtained on multiple
      axial planes with 3T MRA and through-plane velocity profiles were calculated
      under laminar and complicated flow conditions. These velocity profiles were fit
      to a laminar flow model using ordinary least squares in order to quantify the
      degree of flow complication (Matlab). Flow was also measured with a Doppler flow
      probe; vessel diameters and flow velocities were compared with duplex ultrasound
      RESULTS: Carotid artery blood flow was 24.7 +/- 2.6 ml/min prior to stenosis
      creation and reduced to 12.0 +/- 1.7 ml/min following injury (n=3). An MRA voxel
      size of 0.1 x 0.1 x 5 mm was achieved. The control carotid artery diameter was
      1.9 +/- 0.1 mm, and cross-sectional images containing 318 +/- 22 voxels were
      acquired (n=26). Velocity profiles resembled laminar flow proximal to the
      stenosis, and then became more complicated just proximal and distal to the
      stenosis. Laminar flow conditions returned downstream of the stenosis CONCLUSION:
      Implantable, extra-vascular coils enable small MRA voxel sizes to reproducibly
      calculate complex velocity profiles under both laminar and complicated flow in a
      small animal model. This technique may be applied to study blood flow dynamics of
      vessel remodeling and atherogenesis.

PMID- 20036499
TI  - Eligibility for endovascular technique and results of the surgical approach to
      popliteal artery aneurysms at a single center.
AB  - BACKGROUND: Less than 0.1% of the population experiences a popliteal aneurysm
      (PA), and the consequences of not treating PA include a significant risk of
      embolization, thrombosis, and limb loss. Surgical treatment for this vascular
      disease has produced excellent clinical results, but there remain an increasing
      number of published reports that continue to question the efficacy of
      endovascular therapies. METHODS: All consecutive patients operated on for PA at
      our hospital in the years 2000-2007 were reviewed retrospectively for
      clinicopathological data and applicability for endovascular treatment. RESULTS:
      Forty-six patients were surgically treated for 56 PAs (42 vein, 11 alloplastic
      material, and one composite graft). Overall survival rates after 2 and 5 years
      were 77% and 54%, respectively. Reintervention-free survival rates at 2 and 5
      years were 71% and 43%, respectively. Graft patency for veins was significantly
      higher, with a hazard ratio of 0.025 (95% confidence interval 0.002-0.304,
      p=0.004). Twenty-two of the 37 patients (59.5%) with a sufficient angiograph
      appeared to be eligible for endovascular treatment. CONCLUSION: Despite the
      positive results of surgical repair shown in our study and in the existing
      literature, endovascular treatment has a high technical eligibility with good
      reported outcomes and represents an alternative for open surgery.

PMID- 20036501
TI  - WITHDRAWN: Carotid Artery Stenting.
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- 20036500
TI  - Duplication of superficial femoral artery: an uncommon variation of the lower
      limb arterial system.
AB  - The most common anatomical variation of the superficial femoral artery (SFA) is
      hypoplasia or aplasia, associated with persistent sciatic artery. Duplication of
      SFA remains uncommon. We report a case of SFA duplication discovered on an
      angiogram performed for critical limb ischemia, in an 80-year-old man.

PMID- 20036502
TI  - Ligation-and-bypass technique through the posterior approach for bilateral
      popliteal aneurysms.
AB  - A 56-year-old man with a painful, progressively enlarging pulsatile mass in the
      bilateral popliteal fossae was diagnosed with a bilateral popliteal artery
      aneurysm (PAA) and referred to our hospital to undergo surgical therapy. Computed
      tomographic scanning demonstrated a large, middle-type PAA with a rich mural
      thrombus in the bilateral popliteal arteries. Following aneurysm exclusion
      posteriorly, the patient underwent bypass surgery using a ringed
      polytetrafluoroethylene graft bilaterally. This procedure was chosen to prevent
      nerve injury caused by mobilization of the adherent nerves and aneurysmal
      resection. The patient had a satisfactory postoperative course. This procedure
      may be recommended for large, middle-type PAAs because (1) the adherent tibial
      nerve trunk and its branch nerves can be protected by aneurysm exclusion with
      arterial branch ligation and (2) frequently occurring postexclusion expansion of
      the aneurysm caused by insufficient branch ligation using the medial approach can
      be avoided.

PMID- 20036503
TI  - Use of cryopreserved arterial homografts for the treatment of stent infections
      and pseudoaneurysms: regarding "renal artery stent infection and pseudoaneurysm
      management".

PMID- 20036504
TI  - Implantable carotid sinus stimulator for the treatment of resistant hypertension:
      local effects on carotid artery morphology.
AB  - BACKGROUND: The Rheos System is a chronically implanted carotid sinus baroreflex
      activating system with a pulse generator and bilateral perivascular carotid sinus
      leads (CSLs) that is being evaluated in prospective clinical trials for the
      treatment of drug-resistant hypertension. We evaluated carotid artery structural
      integrity after implantation of the CSLs. METHODS: To assess the effect of
      chronic CSL attachment, 29 CSLs were implanted on the common carotid arteries of
      eight sheep. The studies were terminated at 3 and 6 months postimplantation to
      assess anatomic and histologic changes. Additionally, 10 patients with resistant
      hypertension were enrolled in the Rheos Multicenter Feasibility Trial. Duplex
      ultrasound (DUS) was performed before device implantation and at 1 and 4 months
      postimplantation in this patient cohort. An independent core laboratory assessed
      all DUSs. RESULTS: Ovine carotid angiography revealed no significant stenoses,
      while anatomic and histologic evaluations demonstrated electrode encapsulation in
      a thin layer of connective tissue with no evidence of stenosis, erosion, or
      inflammation. DUS evaluation revealed no significant increase in peak systolic
      velocities of the common and internal carotid arteries 1 and 4 months after
      initial implantation, indicating a lack of injury, remodeling, or stenosis.
      CONCLUSION: The current data suggest that the CSLs used with the Rheos System are
      not associated with the development of carotid stenosis or injury. These short
      term data support the concept of CSL placement and merit long-term investigation
      in a larger multicenter prospective trial.

PMID- 20036505
TI  - Acute thrombosis of an abdominal aortic aneurysm followed by delayed rupture
      associated with bacterial infection.
AB  - Sudden thrombosis of an abdominal aortic aneurysm (AAA) is distinctly rare and is
      associated with up to 50% mortality. Almost equally rare is infection of a
      preexisting AAA. We report an extremely unusual case of an AAA that thrombosed
      leading to acute limb ischemia. This was followed several months later by a
      delayed rupture of the thrombosed AAA associated with an Escherichia coli
      infection. We suspect the aortic thrombus was hematogenously seeded by a urinary
      tract infection. A review of the literature revealed that bacterial infection of
      a previously thrombosed AAA, leading to a delayed rupture, has not been
      previously reported.

PMID- 20036506
TI  - Novel surgeon-modified hypogastric branch stent graft to preserve pelvic
      perfusion.
AB  - BACKGROUND: We describe the feasibility and early results of a novel approach to
      preserve pelvic perfusion during endovascular aortic aneurysm repair (EVAR) in
      patients with aortoiliac aneurysms extending to the iliac bifurcation. METHODS:
      Three high-risk patients, aged 70+/-7 years, with large aortoiliac aneurysms
      (mean 6.7+/-0.5 cm) and inadequate distal common iliac artery landing zones were
      treated with a surgeon-modified hypogastric branch stent graft between June 2007
      and July 2008. The modified device was created using a 73 mm iliac stent graft
      limb with a presewn 6-8 mm polyester side graft. The modified device was
      resheathed into a 20F sheath, and the side graft was preloaded with a wire and
      catheter. The resheathed device was introduced to the level of the aortic
      bifurcation via a 24F peel-away sheath, and using the preloaded catheter, a long
      wire was snared, establishing through-and-through femoral access. A 12F
      contralateral femoral sheath was advanced up and over the aortic bifurcation into
      the presewn side graft. The repair was bridged to the ipsilateral hypogastric
      artery using a matting self-expandable stent graft and extended distally to the
      external iliac artery, followed by standard EVAR. All patients were followed
      clinically and with computed tomography angiography prior to hospital discharge
      and every 3 months thereafter. RESULTS: Mean procedural time was 172+/-23 min,
      including 45+/-22 min for device modification. Total fluoroscopy time, contrast
      load, and radiation dose were 78+/-17 min, 180+/-23 mL, and 3,890+/-1,034 mGy,
      respectively. The procedure was technically successful in all cases. There were
      no aneurysm ruptures, deaths, conversions, or complications; and the mean length
      of hospitalization was 3.5+/-1 days. At a mean follow-up of 9+/-3 months, all
      branched hypogastric arteries remained patent without endoleak, migration, or
      loss of device integrity. CONCLUSION: Surgeon-modified hypogastric branch stent
      grafts to maintain perfusion to one or both hypogastric arteries is feasible and
      provides an alternative to hypogastric artery exclusion. Long-term follow-up is
      needed to evaluate stent-graft patency and failure rates.

PMID- 20036507
TI  - Recurrent cystic adventitial disease of the iliofemoral artery.
AB  - We present the case of a 39-year-old man with recurrence of intermittent
      claudication 4 years after successful Dacron patch repair of the right common
      femoral artery for cystic adventitial disease. Magnetic resonance angiography
      results were inconclusive, while conventional angiography demonstrated 90%
      stenosis of the right common femoral artery. The patient underwent excision and
      replacement of the affected artery with PTFE and was asymptomatic at 6-month
      follow-up. In recurrent cystic adventitial disease, excision and replacement of
      the affected artery with a prosthetic interposition graft provides a successful
      outcome with minimal chance of recurrence.

PMID- 20036508
TI  - Trials of endovascular treatment for superficial femoral artery occlusive
      lesions: a call for medically managed control patients.
AB  - BACKGROUND: The prevalence of occlusive peripheral vascular disease in the
      superficial femoral artery approaches 20% in patients over the age of 60.
      Symptomatic peripheral arterial disease (intermittent claudication) is present in
      3% to 7% of patients over the age of 60. The attraction of minimally invasive,
      percutaneous endovascular angioplasty (PTA) for this large number of patients has
      resulted in multiple trials of new PTA +/- stenting devices. The purpose of this
      report is to determine whether trials should include controlled patients who have
      optimal medical management including supervised exercise. METHODS AND RESULTS: In
      2007 through 2008, there were 12 active trials of PTA and stent with 9 of the
      trials randomized and 6 trials using PTA as the control arm. No trial used a
      medically managed group. Between 1990 and 2008, a search of PubMed disclosed six
      publications (five randomized trials) comparing PTA +/- stent with medically
      (exercise) managed claudicants. None of the medically managed patient groups
      experienced a significant increase in ABI, whereas endovascular patients had an
      early increase in ABI, which was variably sustained to 1 and 2 years. However,
      after 6 months, the maximum walking distance was significantly increased in the
      exercised patients and remained longer than that of the interventional group in
      four of five trials at 1 to 2 years. CONCLUSION: Endovascular treatment was
      superior to medical treatment in functional outcome at 1 year in only one of the
      five randomized trials for claudication. In the other four trials, medical
      treatment produced a greater maximum walking distance at 1 to 2 years. Current
      trials lack optimal medical controls. New trials of PTA + stent should include a
      medically managed group of patients in a supervised exercise program as the
      comparator arm. The outcome measure should be maximum walking distance to
      demonstrate added functional benefit of the new device.

PMID- 20036509
TI  - Endovascular treatment of massive thoracic aortic thrombus and associated
      ruptured atheroma.
AB  - Atheroembolic disease typically presents with isolated lower extremity digital
      ischemia. Treatment traditionally includes optimization of medical management,
      with open surgery reserved for complicated or recurrent embolic events. We
      present a novel endovascular approach for treatment of complicated thoracic
      aortic atherosclerotic disease incidentally discovered in a 63-year-old female.
      The patient demonstrated visceral artery embolization from a mobile 2.6 cm
      atherosclerotic plaque despite maximal medical therapy. Thoracic aortic stent
      graft placement successfully excluded the atheroma and prevented further
      embolization. This case demonstrates a unique treatment option for complicated
      thoracic aortic atheroembolic disease utilizing a minimally invasive endovascular
      approach.

PMID- 20036511
TI  - Postoperative management for PIP joint pyrocarbon arthroplasty.
AB  - Although protocols provide therapists with the scaffolding with which to build a
      treatment program, it is the judgment, knowledge, and skills of the therapist,
      and how the one uses such information that allows for modification of a protocol
      when deemed necessary. This therapist outlines how she modified a postsurgical
      protocol by using anatomy, biomechanics, the literature, and clinical judgment.
      This article describes the methodical approach used to successfully modify a
      standard postsurgical protocol after a PIP joint arthroplasty.

PMID- 20036510
TI  - Aneurysmectomy with arterial reconstruction of renal artery aneurysms in the
      endovascular era: a safe, effective treatment for both aneurysm and associated
      hypertension.
AB  - BACKGROUND: Renal artery aneurysms (RAAs) represent a rare vascular pathology
      with an estimated incidence of <1%. Although an endovascular approach is being
      increasingly used to treat RAAs, we hypothesized that open surgical repair of
      RAA, specifically via aneurysmectomy with arterial reconstruction (AAR), is a
      safe, effective treatment, particularly for those with complex aneurysm anatomy.
      METHODS: A review was performed of all patients with RAA, identified by ICD-9
      codes, from January 2003 to December 2008 seen at a tertiary care medical center.
      Data were collected regarding patient demographics, aneurysm characteristics,
      surgical repair, and outcomes, as well as follow-up care. RESULTS: A total of 14
      patients (10 women and 4 men; mean age, 48+/-19 years) were included,
      representing 15 aneurysms. Ten aneurysms underwent open repair via AAR and five
      were followed nonoperatively. Mean RAA size was larger for those undergoing
      repair (2.12 cm vs. 1.62 cm, p=0.037). Seven RAAs were repaired in situ with
      either patch angioplasty or primary repair; three required ex vivo
      reconstruction; and none underwent bypass. Average operative time was similar for
      repair type, with a higher blood loss with ex vivo repair. Median length of stay
      was 5 days (range, 4 to 14 days). Operative repair had no effect on mean systolic
      blood pressure or GFR. This repair, however, resulted in lower medication
      requirement for those with concurrent hypertension (2.7 pre vs. 1.6 post,
      p=0.03). There was a trend toward shorter time until oral intake for
      retroperitoneal approach compared with transperitoneal. Mean follow-up time was
      11.6 months (range, 3 to 30 months). No incidences of rupture, death,
      nephrectomy, or renal failure occurred in the operative group. CONCLUSION: In the
      era of endovascular repairs for RAAs, open repair, specifically via AAR, of RAAs
      remains a safe treatment with low associated morbidity. RAA repair resulted in a
      reduction in medications for those with associated hypertension. Open repair of
      RAAs should be the primary treatment modality for complex RAA, with specific
      consideration given to those with associated hypertension.

PMID- 20036512
TI  - Screening for gastrointestinal, hepatic/biliary, and renal/urologic disease.
AB  - NARRATIVE REVIEW: Many organ systems in the body can demonstrate signs and
      symptoms of impairment that mimic integumentary, musculoskeletal, and/or
      neuromuscular conditions commonly evaluated and treated by the hand therapist. In
      this review, diseases and disorders affecting the gastrointestinal (GI),
      hepatic/biliary, and renal/urologic systems capable of referring pain and other
      symptoms to the upper quadrant are presented. Specifically, these organ systems
      can refer pain to the sternum, neck, shoulder, scapulae, and subscapular and
      interscapular regions. Symptom referral from the viscera to the elbow and hand is
      extremely rare. Symptoms of carpal tunnel syndrome/paresthesias can occur in
      renal disorders and with hepatic/biliary problems. Following the screening model
      proposed by Goodman and Snyder, potential origins from the GI, hepatic/biliary,
      and renal/urologic systems are discussed. The goal is to identify patients with
      referred pain patterns and associated signs and symptoms of conditions that
      require referral to a physician or other appropriate health care professional.
      The alert hand therapist will recognize red flag histories, clinical
      presentation, and risk factors suggesting the need for a more thorough
      examination to ensure that the patient/client has a condition requiring
      intervention that is within the scope of the therapist's practice. Screening
      principles and tips for physician referral are offered. LEVEL OF EVIDENCE: 5.

PMID- 20036513
TI  - Brain perfusion heterogeneity measurement based on Random Walk algorithm: choice
      and influence of inner parameters.
AB  - A Random Walk (RW) algorithm was designed to quantify the level of diffuse
      heterogeneous perfusion in brain SPECT images in patients suffering from systemic
      brain disease or from drug-induced therapy. The goal of the present paper is to
      understand the behavior of the RW method on different kinds of images (extrinsic
      parameters) and also to understand how to choose the right parameters of the RW
      (intrinsic parameters) depending on the image characteristics (i.e. SPECT
      images). "Extrinsic parameters" are related to the image characteristics
      (level/size of defect and diffuse heterogeneity) and "intrinsic" parameters are
      related to the parameters of the method (number (N(rw)) and length of walk
      (L(rw)), temperature (T) and slowing parameter (S)). Two successive studies were
      conducted to test the influence of these parameters on the RW result. In the
      first study, calibrated checkerboard images are used to test the influence of
      "extrinsic parameters" (i.e. image characteristics) on the RW result (R-value).
      The R-value was tested as a function of (i) the size of black & white (B&W)
      squares simulating the size of a cortical defect, (ii) the intensity level gaps
      between the B&W squares simulating the intensity of the cortical defect and (iii)
      intensity (=variance) of noise, simulating the diffuse heterogeneity. The second
      study was constructed with simulated representative brain SPECT images, to test
      the "intrinsic" parameters. The R-value was tested regarding the influence of
      four parameters: S, T, N(rw) and L(rw). The third study is constructed so as to
      see if the classification by diffuse heterogeneity of real brain SPECT images is
      the same if it's made by senior clinicians or by RW algorithm. RESULTS: Study 1:
      the RW was strongly influenced by all the characteristics of the images.
      Moreover, these characteristics interact with each other. The RW is influenced
      most by diffuse heterogeneity, then by intensity and finally by the size of a
      defect. Study 2: N(rw) and L(rw) values of 1000 give an optimal reproducibility
      of the measurement (mean standard deviation<0.1), a fast computation time
      (time<0.5s/image) and have a maximum difference in terms of R-value between the
      two extreme images corresponding to the range of the population studied. The best
      S and T values for SPECT images are 3 and 15, respectively. Study 3: A
      significant correlation was found between RW ranking and the physicians'
      consensus (rho=0.789; p<0.0001). CONCLUSION: This study confirms that the RW
      method is able to measure the heterogeneity of brain SPECT images even in the
      presence of a large defect. However, the result of the method is strongly
      influenced by the "intrinsic" parameters, so the program should be calibrated for
      each different type of image.

PMID- 20036514
TI  - A 4-year survey of the activity of a malnutrition task force in an Italian
      research hospital.
AB  - OBJECTIVE: The proper management of nutritional support remains a challenging
      task in many Western hospitals. This study aimed at reporting a 4-y survey on the
      centralized management of nutritional support by a malnutrition task force in an
      Italian research hospital. METHODS: The requests for nutritional supports, the
      number of patients treated with enteral nutrition in the medical and surgical
      units, and the number of home artificial nutritional support activated were
      recorded from 2005 to 2008. RESULTS: The median number of first and follow-up
      visits per month significantly increased from 16 (25th-75th percentiles 13-26) in
      2005 to 74 (25th-75th percentiles 69-82) in 2008 (P < 0.001) and from 56 (25th
      75th percentiles 42-82) in 2005 to 101 (25th-75th percentiles 90-120) in 2008 (P
      = 0.001), respectively. This trend was observed also in the number of patients
      treated with enteral nutrition (from 95 in 2004 to 190 in 2008) and in those on
      home artificial nutritional support (from 25 in 2004 to 65 in 2008), whereas the
      number of parenteral nutrition bags produced remained substantially stable.
      CONCLUSION: The centralized management of nutritional support is a successful
      strategy, which provides the appropriate prescription of artificial nutrition
      during hospitalization and at discharge. Multidisciplinary nutrition support
      teams or task forces should be created in every hospital.

PMID- 20036515
TI  - Height prediction formula for middle-aged (30-55 y) Caucasians.
AB  - OBJECTIVE: Stature is essential for nutritional assessment but direct measurement
      is not possible in bed-ridden patients. Height prediction models have been
      developed for elderly persons but none is available for middle-aged people. We
      aimed to validate new equations for height prediction in middle-aged adults.
      METHODS: Middle-aged (30-55 y) adults (n = 635, 316 men, 319 women) were studied
      for anthropometry (weight, standing height, knee height, and tibia length) and
      body composition (fat-free mass by impedance). The effect of estimated height on
      the derivation of body mass index and surface area, fat-free mass, and resting
      energy expenditure was evaluated. Multiple regressions analyzed the covariates in
      stature prediction. The best model was selected according to the highest R(2)
      value and the lowest root mean square error. RESULTS: We obtained a model valid
      for men and women that included age, knee height, and gender (R(2) = 0.89, root
      mean square error = 3.2 cm, limits of agreement -6.1 to 6.5 cm). The use of
      estimated height in the calculation of body mass index, body surface area, fat
      free mass, and REE produced acceptable biases. Application of the model to a
      control sample resulted in pure errors comparable to root mean square errors of
      the validation sample. In addition, the use of nationally representative models,
      introduced for elderly persons by Chumlea et al. (J Am Diet Assoc 1998;98:137
      42), appeared to produce similar but slightly higher biases in both sexes.
      CONCLUSION: In middle-aged Caucasians, height can be estimated with acceptable
      accuracy by the model proposed in this report. The derivation of body mass index,
      body surface area, fat-free mass, and resting energy expenditure by this estimate
      is accurate. Nevertheless, in the absence of more accurate age- and race-specific
      prediction models, the use of equations by Chumlea et al. should always be
      considered.

PMID- 20036516
TI  - Study of lymphocyte subpopulations in bone marrow in a model of protein-energy
      malnutrition.
AB  - OBJECTIVE: Protein-energy malnutrition (PEM) is an important public health
      problem affecting millions of people worldwide. Hematopoietic tissue requires a
      high nutrient supply, and a reduction in leukocytes, especially lymphocytes,
      suggests that some nutritional deficiencies might be altering bone marrow
      function and decreasing its ability to produce lymphocytes. In this study, we
      evaluated the effect that PEM has on lymphocyte subtypes and the cell cycle of
      CD5(+) cells. METHODS: Swiss mice were subjected to PEM using a low-protein diet
      containing 4% protein. When the experimental group had lost about 20% of their
      original body weight, we collected blood and bone marrow cells and evaluated the
      hemogram, the myelogram, bone marrow lymphoid markers using flow cytometry, and
      the cell cycle in CD5(+) bone marrow. RESULTS: Malnourished animals presented
      anemia, reticulocytopenia, and leukopenia with lymphopenia. The bone marrow was
      hypocellular, and flow cytometric analyses of bone marrow cells showed cells that
      were CD45(+) (91.2%), CD2(+) (84.9%), CD5(+) (37.3%), CD3(+) (23.5%), CD19(+)
      (43.3%), CD22(+) (34.7%), CD19(+)/CD2(+) (51.2%), CD19(+)/CD3(+) (24.0%),
      CD19(+)/CD5(+) (13.2%), CD22(+)/CD2(+) (40.1%), CD22(+)/CD3(+) (30.3%), and
      CD22(+)/CD5(+) (1.1%) in malnourished animals and CD45(+) (97.5%), CD2(+)
      (42.9%), CD5(+) (91.5%), CD3(+) (92.0%), CD19(+) (52.0%), CD22(+) (75.6%),
      CD19(+)/CD2(+) (62.0%), CD19(+)/CD3(+) (55.4%), CD19(+)/CD5(+) (6.7%),
      CD22(+)/CD2(+) (70.3%), CD22(+)/CD3(+) (55.9%), and CD22(+)/CD5(+) (8.4%) in
      control animals. Malnourished animals also presented more CD5(+) cells in the G0
      phase of cell cycle development. CONCLUSION: Malnourished animals presented bone
      marrow hypoplasia, maturation interruption, prominent lymphopenia with depletion
      in the lymphoid lineage, and changes in cellular development. We suggest that
      these changes are some of the primary causes of lymphopenia in cases of PEM and
      partly explain the increase in susceptibility to infections found in malnourished
      individuals.

PMID- 20036518
TI  - Characterisation of breakthrough invasive mycoses in echinocandin recipients: an
      evidence-based review.
AB  - The echinocandins have emerged as important antifungal agents in the current era.
      Despite their potent antifungal activity, breakthrough invasive mycoses occur in
      echinocandin recipients, however their precise incidence and causative pathogens
      are not well delineated. This review shows that breakthrough mycoses occur in
      2.4% of patients receiving echinocandins as prophylaxis and are predominantly due
      to non-albicans Candida spp. and less frequently to invasive aspergillosis.
      Candida isolates demonstrating reduced susceptibility occurred following
      prolonged exposure to the echinocandins, primarily in severely immunocompromised
      patients, and manifested as recurrent episodes of candidaemia or invasive
      candidiasis.

PMID- 20036517
TI  - Methionine-deficient diet induces post-transcriptional downregulation of
      cystathionine beta-synthase.
AB  - OBJECTIVE: Elevated plasma total homocysteine (tHcy) is a risk factor for a
      variety of human diseases. Homocysteine is formed from methionine and has two
      primary metabolic fates: remethylation to form methionine or commitment to the
      transsulfuration pathway by the action of cystathionine beta-synthase (CBS). We
      have examined the metabolic response in mice of a shift from a methionine-replete
      to a methionine-free diet. METHODS AND RESULTS: We found that shifting 3-mo-old
      C57BL6 mice to a methionine-free diet caused a transient increase in tHcy and an
      increase in the tHcy/methionine ratio. Because CBS is a key regulator of tHcy, we
      examined CBS protein levels and found that within 3 d on the methionine-deficient
      diet, animals had a 50% reduction in the levels of liver CBS protein and enzyme
      activity. Examination of CBS mRNA and studies of transgenic animals that express
      CBS from a heterologous promoter indicated that this reduction is occurring post
      transcriptionally. Loss of CBS protein was unrelated to intracellular levels of S
      adenosylmethionine, a known regulator of CBS activity and stability. CONCLUSION:
      Our results imply that methionine deprivation induces a metabolic state in which
      methionine is effectively conserved in tissue by shutdown of the transsulfuration
      pathway by an S-adenosylmethionine-independent mechanism that signals a rapid
      downregulation of CBS protein.

PMID- 20036519
TI  - Susceptibility patterns and molecular epidemiology of multidrug-resistant
      Acinetobacter baumannii strains from three military hospitals in China.
AB  - To date, little has been reported on the susceptibility patterns and molecular
      characterisation of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical
      isolates from different Chinese military hospitals. In this study, 49 MDRAB
      strains were collected from three military hospitals during 2007. The minimum
      inhibitory concentrations (MICs) of 13 antibiotics were determined for each
      strain. Genotyping and dendrogram analysis of MDRAB strains were performed using
      the repetitive sequence-based polymerase chain reaction (rep-PCR) DiversiLab
      Microbial Typing System. PCR screening was carried out to investigate the
      distribution of various genes contributing to each resistance phenotype in the
      main clonal types. The rates of resistance to the majority of antibiotics tested
      varied between 75.5% and 100%, with the exception of polymyxin B. Two DiversiLab
      rep-PCR clones (A and B) were widespread in three hospitals in different cities,
      one clone (D) existed only in two hospitals located in the same city (Beijing),
      and the other two clones (C and E) were present in only one hospital. In
      addition, this study shows a high distribution of intI1, ISAba1, bla(OXA-23),
      bla(ADC), adeB, adeJ, abeM and tet(B) genes, which mediate resistance to
      structurally unrelated antimicrobials in MDRAB isolates. These results suggest
      that all isolates were resistant to at least three classes of antibiotics. In
      addition, clonal dissemination among the three hospitals located in two different
      cities in China, previously documented in many regions of Europe and Asia-Pacific
      nations, emphasises the epidemic potential of these MDRAB isolates.

PMID- 20036520
TI  - Evaluation of the activity of fusidic acid tested against contemporary Gram
      positive clinical isolates from the USA and Canada.
AB  - We evaluated the antimicrobial activity of fusidic acid (CEM-102) against 1140
      clinical strains of Gram-positive bacteria obtained from patients with
      bacteraemia or skin and skin-structure infections collected in more than 30
      medical centres in the USA and Canada over a 10-year period (1997-2006). Fusidic
      acid was very active against meticillin-susceptible Staphylococcus aureus (MSSA),
      meticillin-resistant S. aureus (MRSA) and coagulase-negative staphylococci
      (CoNS), with MIC(90) values (minimum inhibitory concentration encompassing 90% of
      isolates tested) at 0.12mug/mL for US strains of MSSA, MRSA and CoNS and
      0.25mug/mL for Canadian strains of MSSA and MRSA. A progressive increase in
      fusidic acid resistance was observed among Canadian strains of S. aureus (12.2%
      in 2005-2006) and among Canadian strains of CoNS. In contrast, no fusidic acid
      resistance was detected among US S. aureus strains and only 1.5% among CoNS.
      Fusidic acid was equally active against community-acquired MRSA and linezolid
      resistant staphylococci. Fusidic acid exhibited equal or greater potency against
      staphylococci compared with vancomycin, daptomycin and linezolid.

PMID- 20036521
TI  - Adsolubilization of drugs onto natural clinoptilolite modified by adsorption of
      cationic surfactants.
AB  - The combined adsorption onto purified natural clinoptilolite (NZ) of the cationic
      surfactant benzalkonium chloride (BC) and the model drugs metronidazole and
      sulfamethoxazole has been studied in order to design systems for the storage and
      release of drugs. The equilibrium adsorption of benzyldimethylalkylammonium
      chloride surfactants with hydrocarbon chain lengths corresponding to 12, 14 and
      16 carbon atoms (BC12, BC14 and BC16) onto NZ from aqueous solutions was compared
      to that of BC. The effect of exchangeable cations on the NZ structure and that of
      acid-base pre-treatment of NZ on the adsorption capacity of BC was evaluated. It
      was shown that the nature of the exchangeable cations had little influence on the
      adsorption of BC onto NZ, and that acid-base treatments of NZ led to a decrease
      in the amount of surfactant adsorbed. The results indicated that the adsorption
      of the less polar drug, sulfamethoxazole, was enhanced by the presence of BC12 at
      the solid-liquid interface, whereas the uptake of metronidazole was independent
      of the surfactant adsorption.

PMID- 20036522
TI  - Hierarchically organized layout for visualization of biochemical pathways.
AB  - OBJECTIVE: Many complex pathways are described as hierarchical structures in
      which a pathway is recursively partitioned into several sub-pathways, and
      organized hierarchically as a tree. The hierarchical structure provides a natural
      way to visualize the global structure of a complex pathway. However, none of the
      previous research on pathway visualization explores the hierarchical structures
      provided by many complex pathways. In this paper, we aim to develop algorithms
      that can take advantages of hierarchical structures, and give layouts that
      explore the global structures as well as local structures of pathways. METHODS:
      We present a new hierarchically organized layout algorithm to produce layouts for
      hierarchically organized pathways. Our algorithm first decomposes a complex
      pathway into sub-pathway groups along the hierarchical organization, and then
      partition each sub-pathway group into basic components. It then applies
      conventional layout algorithms, such as hierarchical layout and force-directed
      layout, to compute the layout of each basic component. Finally, component layouts
      are joined to form a final layout of the pathway. Our main contribution is the
      development of algorithms for decomposing pathways and joining layouts. RESULTS:
      Experiment shows that our algorithm is able to give comprehensible visualization
      for pathways with hierarchies, cycles as well as complex structures. It clearly
      renders the global component structures as well as the local structure in each
      component. In addition, it runs very fast, and gives better visualization for
      many examples from previous related research.

PMID- 20036523
TI  - Bactericidal and anti-inflammatory properties of a standardized Echinacea extract
      (Echinaforce): dual actions against respiratory bacteria.
AB  - Common symptoms of upper respiratory infections, such as sore throat, cough, and
      inflammation, are often caused by bacteria, sometimes as a complication of virus
      infection. Extracts of Echinacea purpurea (Asteraceae) have been advocated
      traditionally for use by individuals suffering from these symptoms, although the
      underlying basis for the beneficial effects of Echinacea is not known. We
      hypothesized that Echinacea could inactivate certain respiratory bacteria and
      could also reverse inflammatory effects caused by these bacteria in epithelial
      cells. In order to test this we used a commercial standardized extract of
      Echinacea purpurea (Echinaforce), and a novel cytokine array system designed to
      measure simultaneously the levels of 20 different cytokines secreted by bronchial
      epithelial cell cultures in response to infection. Streptococcus pyogenes (Group
      A Strep), which is often associated with sore throat and more severe pulmonary
      infections, was readily inactivated by Echinacea, which also completely reversed
      the cellular pro-inflammatory response. Hemophilus influenzae and Legionella
      pneumophila were also readily inactivated, and their pro-inflammatory responses
      reversed. Staphylococcus aureus (methicillin-resistant and sensitive strains) and
      Mycobacterium smegmatis were less sensitive to the bactericidal effects of
      Echinacea however, but their pro-inflammatory responses were still completely
      reversed. In contrast some other pathogens tested, including Candida albicans,
      were relatively resistant. Thus Echinaforce) exerts a dual action against several
      important respiratory bacteria, a killing effect and an anti-inflammatory effect.
      These results support the concept of using a standardized Echinacea preparation
      to control symptoms associated with bacterial respiratory infections.

PMID- 20036524
TI  - Non-response in epidemiological studies - How to cope with it?

PMID- 20036525
TI  - Comparison of eNO and histamine hyperresponsiveness in diagnosing asthma in new
      referrals.
AB  - The mainstay of the diagnosis of asthma is the presence of reversible airway
      obstruction. Exhaled NO levels are increased in asthma, in close relationship
      with the amount of airway inflammation, and may be used for monitoring the
      disease and adjusting therapy. In this study we investigated the role of eNO as a
      diagnostic for asthma, compared with the FEV1-reversibility and the PC20 (20%
      decrease of the FEV1 in the bronchial histamine provocation test), in two
      independent centers, on an unselected population. ENO measurements were performed
      with chemoluminesence technique in one center and with an electrochemical device
      in the other. Only after correction for so-called nuisance factors (allergy, use
      of inhaled steroids, recent infection, smoking, sex and the use of nitrate food)
      the eNO appeared as a diagnostic with equal power as the FEV1-reversibility and
      the PC20. Therefore, screening for asthma in our study population, with the eNO
      measurement, is a simple, fast and safe strategy.

PMID- 20036526
TI  - Young people and drugs: next generation of harm reduction.
AB  - Globally, young people under 25 accounted for an estimated 45% of all new HIV
      infections in 2007. Across the Eastern Europe and Central Asia region as many as
      25% of injecting drug users (IDUs) are younger than 20. The Eurasian Harm
      Reduction assessment of young peoples' (under 25) drug use, risk behaviours and
      service availability and accessibility confirms, young people at risk of
      injecting, or those already experimenting with injecting drugs, find themselves
      isolated from health and prevention services, which increases the risks for
      health and social harms, while the approach towards young peoples' use rely
      heavily on law enforcement. Denying young drug users' access to life-saving drug
      treatment and other harm reduction services contributes to the risk environment
      surrounding their use and violates their right to health and well-being as
      identified in the Convention on the Rights of the Child. Governments, health care
      providers and harm reduction services should work together to create an
      environment in which young people can access needed services, including non
      judgmental and low-threshold approaches offered by harm reduction programs.

PMID- 20036527
TI  - Opportunities for enhancing and integrating HIV and drug services for drug using
      vulnerable populations in South Africa.
AB  - BACKGROUND: Little has been done to improve the integration of drug use and HIV
      services in sub-Saharan Africa where substance use and HIV epidemics often co
      exist. METHODS: Data were collected using rapid assessment methods in two phases
      in Cape Town, Durban and Pretoria, South Africa. Phase I (2005) comprised 140 key
      informant and focus group drug using interviewees and 19 service providers (SPs),
      and Phase 2 (2007) comprised 69 drug using focus group interviewees and 11 SPs.
      RESULTS: Drug users put themselves at risk for HIV transmission through various
      drug-related sexual practices as well as through needle sharing. Drug users in
      both phases had limited knowledge of the availability of drug treatment services,
      and those that had accessed treatment identified a number of barriers, including
      affordability, stigma and a lack of aftercare and reintegration services. SPs
      identified similar barriers. Drug users displayed a general awareness of both HIV
      transmission routes and prevention strategies, but the findings also indicated a
      number of misperceptions, and problematic access to materials such as condoms and
      safe injection equipment. Knowledge around HIV treatment was low, and VCT
      experiences were mixed. SPs recognized the importance of integrating HIV and
      substance use services, but barriers such as funding issues, networking/referral
      gaps and additional burden on staff were reported in Phase 2. CONCLUSION: A
      comprehensive, accessible, multi-component intervention strategy to prevent HIV
      risk in drug users needs to be developed including community outreach, risk
      reduction counselling, VCT and substance use treatment.

PMID- 20036528
TI  - Determination of charge transfer resistance and capacitance of microbial fuel
      cell through a transient response analysis of cell voltage.
AB  - An alternative method for determining the charge transfer resistance and double
      layer capacitance of microbial fuel cells (MFCs), easily implemented without a
      potentiostat, was developed. A dynamic model with two parameters, the charge
      transfer resistance and double-layer capacitance of electrodes, was derived from
      a linear differential equation to depict the current generation with respect to
      activation overvoltage. This model was then used to fit the transient cell
      voltage response to the current step change during the continuous operation of a
      flat-plate type MFC fed with acetate. Variations of the charge transfer
      resistance and the capacitance value with respect to the MFC design conditions
      (biocatalyst existence and electrode area) and operating parameters (acetate
      concentration and buffer strength in the catholyte) were then determined to
      elucidate the validity of the proposed method. This model was able to describe
      the dynamic behavior of the MFC during current change in the activation loss
      region; having an R(2) value of over 0.99 in most tests. Variations of the charge
      transfer resistance value (thousands of Omega) according to the change of the
      design factors and operational factors were well-correlated with the
      corresponding MFC performances. However, though the capacitance values
      (approximately 0.02 F) reflected the expected trend according to the electrode
      area change and catalyst property, they did not show significant variation with
      changes in either the acetate concentration or buffer strength.

PMID- 20036529
TI  - Active and passive cigarette smoking and the risk of endometrial cancer in
      Poland.
AB  - BACKGROUND: Epidemiological studies have consistently reported that active
      cigarette smoking is inversely associated with endometrial cancer risk. However,
      dose-response relationships with quantitative measures of active smoking or
      passive smoking remain less clear. METHODS: Data on lifetime active and passive
      smoking were collected for 551 endometrial cancer cases and 1925 controls in a
      population-based case-control study conducted during 2001-2003 in Poland (Warsaw
      and Lodz). RESULTS: Compared with never active smokers, active current (Odds
      Ratio (OR)=0.51, 95% Confidence Interval (CI): 0.39, 0.68) and former smokers
      (OR=0.60, 95% CI: 0.45, 0.80) were at a statistically significantly decreased
      risk. We did not observe statistically significant inverse dose-response
      relationships with increasing exposure with duration and cumulative measures.
      However, there was some indication that the highest category of number of years
      (OR=0.35, 95% CI: 0.23-0.55), intensity (OR=0.41, 95% CI: 0.24-0.69), and dose
      (OR=0.38, 95% CI: 0.24-0.60) of smoking among current smokers had the greatest
      inverse association compared to never smokers. Our data did not support the
      presence of an inverse association with passive smoking among never active
      smokers (OR=0.92; 95% CI: 0.65, 1.29). CONCLUSION: Our results support that long
      term and heavy smoking among current smokers strongly influence endometrial
      cancer risk.

PMID- 20036530
TI  - From cancer patients to cancer survivors: the issue of Cardioncology--a
      biological perspective.
AB  - Long-term survival of cancer patients can be worsened by cardiovascular morbidity
      and mortality due to anticancer treatments based on cardiotoxic or antiangiogenic
      regimens. Growing scientific evidences support a role for circulating endothelial
      progenitor cells (EPCs) both in cancer pathogenesis and in cardiovascular
      diseases. High frequency of circulating EPCs seems to play a role in cancer
      growth and dissemination by favouring tumor angiogenesis and estabilishment of
      sites of metastasis. On the other hand, high level of circulating EPCs seems to
      be associated with a lower risk of developing cardiovascular diseases and with
      improved vascular regeneration after cardiovascular damage. Here, the possibile
      opposing roles of circulating EPCs in cancer patients suffering from therapy
      related-cardiovascular diseases are discussed, under the light of the potential
      modulation of their levels for therapeutic purposes. This can become a relevant
      issue in the field of cardioncology, the discipline that deals with the managing
      and treatment of cancer patients suffering from concomitant cardiovascular
      diseases or who are exposed to an increased risk to develop therapy related
      cardiovascular complications.

PMID- 20036531
TI  - Geriatric syndromes in peri-operative elderly cancer patients.
AB  - Due to the expanding geriatric population and the high incidence of cancer in
      this age group, there is an increased burden on clinical oncologists. Elderly
      patients suffer from one or more chronic diseases, especially cardiovascular
      diseases, COPD, or diabetes. Besides affecting life expectancy, comorbid
      conditions may complicate major surgery. Accurate prediction of surgical risk is
      of paramount importance. Numerous papers have documented that older patients can
      undergo surgery with similar cancer related survival to younger patients. It has
      been demonstrated that age related variables are associated with an increased
      risk in post-surgical complications. The term "geriatric syndrome" needs further
      clinical evaluation and understanding. It is used to capture those clinical
      conditions in older persons that do not fit into discrete disease categories.
      Geriatric syndromes including delirium, falls, frailty, dizziness, syncope and
      urinary incontinence, are among the most common conditions facing geriatricians.
      This article focuses on geriatric syndromes in post-surgical patients and their
      management.

PMID- 20036532
TI  - Effectiveness of inoculation with isolated Geobacillus strains in the
      thermophilic stage of vegetable waste composting.
AB  - An inoculum containing two amylolytic and three cellulolytic thermophilic
      bacteria, isolated from a preceding compost pile and identified as Geobacillus
      species by 16S rRNA gene sequencing, was applied to a mixture of market waste,
      rice straw and cow dung (5:1:0.2) so that the initial cell density was 2 x 10(8)
      colony forming unit (CFU) per gram dry weight at 55 degrees Celsius. The
      inoculation increased the total cell count particularly in the thermophilic stage
      as determined by flow cytometry. Concomitantly, there was a significant rise in
      microbial metabolism in the compost pile as reflected by the dehydrogenase
      activity. As a result, the C/N ratio dropped more rapidly in the inoculated
      mixture than that in the control without inoculum. The study, therefore,
      suggested that inoculation by thermophilic bacteria would be effective in the
      composting process at least in the thermophilic stage.

PMID- 20036533
TI  - Synergistic effects between aminoethyl-chitosans and beta-lactams against
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Two kinds of aminoethyl-chitosans (AEC), AEC90 and AEC50, which had degrees of
      deacetylation of 90% and 50%, respectively, were prepared and their synergistic
      effects in combination with beta-lactams including ampicillin, penicillin, and
      oxacillin against two standard methicillin-resistant Staphylococcus aureus (MRSA)
      strains and twelve clinical isolated MRSA strains were investigated. When AECs
      and beta-lactams were combined, synergistic effects were observed with fractional
      inhibitory concentration (FIC) indices of 0.252-0.508, and the MICs of beta
      lactams in the presence of AECs were dramatically reduced.

PMID- 20036534
TI  - Synthesis and antifungal activities in vitro of novel pyrazino [2,1-a]
      isoquinolin derivatives.
AB  - A series of novel pyrazino[2,1-a]isoquinolin compounds were designed and
      synthesized, and their antifungal activities in vitro were evaluated. The results
      showed that all of the compounds exhibited antifungal activities. Some of them
      exhibited stronger antifungal activities than that of lead compounds and among
      them compound 11b was the most potent one, which showed more potent than that of
      the active control fluconazole to the four of the five tested fungi. The studies
      presented here provide a new structural type for the development of novel
      antifungal agents.

PMID- 20036535
TI  - Cyclic diarylheptanoids as Na+-glucose cotransporter (SGLT) inhibitors from Acer
      nikoense.
AB  - Two cyclic diarylheptanoids, acerogenins A (1) and B (2) have been isolated from
      the bark of Acer nikoense as inhibitors of Na(+)-glucose cotransporter (SGLT).
      Acerogenins A (1) and B (2) inhibited both isoforms, SGLT1 and SGLT2. Structure
      activity relationship of acerogenin derivatives on inhibitory activity of SGLT as
      well as conformational analysis of 1 and 2 on the basis of J-resolved HMBC
      spectra and X-ray analysis were discussed.

PMID- 20036536
TI  - Oxime carbamate--discovery of a series of novel FAAH inhibitors.
AB  - A series of novel oxime carbamates have been identified as potent inhibitors of
      the key regulatory enzyme of the endocannabinoid signaling system, fatty acid
      amide hydrolase (FAAH). In this Letter, the rationale behind the discovery and
      the biological evaluations of this novel class of FAAH inhibitors are presented.
      Both in vitro and in vivo results of selected targets are discussed, along with
      inhibition kinetics and molecular modeling studies.(1).

PMID- 20036537
TI  - Antitumor agents. 271: total synthesis and evaluation of brazilein and analogs as
      anti-inflammatory and cytotoxic agents.
AB  - The first total synthesis of the naturally occurring tetracyclic homoisoflavonoid
      brazilein (1) and 14 new analogs (1a-n) is reported. Target compounds and
      intermediates were assayed for anti-inflammatory effects on superoxide anion
      generation and elastase release by human neutrophils in response to fMLP/CB, and
      for cytotoxic activity against nasopharyngeal (KB), vincristine-resistant
      nasopharyngeal (KBvin), lung (A549) and prostate (DU-145) human cancer cell
      lines. The most active compound 1b showed potent effects on superoxide anion
      generation and elastase release with IC(50) values of 1.2 and 1.9 microM,
      respectively, and was 65 times more potent than phenylmethylsulfonyl fluoride
      (PMSF), the positive control, in the latter assay. Additionally, 1b exhibited
      broad spectrum in vitro anticancer activity with IC(50) values of 6-11 microM
      against the four tested cancer cell lines.

PMID- 20036538
TI  - Visual enhancement of the information representation in auditory cortex.
AB  - Combining information across different sensory modalities can greatly facilitate
      our ability to detect, discriminate, or recognize sensory stimuli. Although this
      process of sensory integration has usually been attributed to classical
      association cortices, recent work has demonstrated that neuronal activity in
      early sensory cortices can also be influenced by cross-modal inputs. Here we
      demonstrate that such "early" multisensory influences enhance the information
      carried by neurons about multisensory stimuli. By recording in auditory cortex of
      alert monkeys watching naturalistic audiovisual stimuli, we quantified the effect
      of visual influences on the trial-to-trial response variability and on the amount
      of information carried by neural responses. We found that firing rates and
      precisely timed spike patterns of individual units became more reliable across
      trials and time when multisensory stimuli were presented, leading to greater
      encoded stimulus information. Importantly, this multisensory information
      enhancement was much reduced when the visual stimulus did not match the sound.
      These results demonstrate that multisensory influences enhance information
      processing already at early stages in cortex, suggesting that sensory integration
      is a distributed process, commencing in lower sensory areas and continuing in
      higher association cortices.

PMID- 20036539
TI  - Visual targeting of forelimbs in ladder-walking locusts.
AB  - Accurate limb placement helps animals and robots to walk on substrates that are
      uneven or contain gaps. Visual information is important in controlling limb
      placement in walking mammals but has received little attention in insects. We
      investigated whether desert locusts walking along a horizontal ladder use vision
      to control limb placement. High-speed video analysis showed that locusts targeted
      their front legs to specific rungs in the absence of any previous contact,
      suggesting that visual information alone is sufficient for targeting single
      steps. Comparison between the proportions of missed steps before and after
      monocular occlusion showed that monocular visual information was used to place
      the ipsilateral but not the contralateral front leg. Accurate placement also
      depended upon mechanosensory inputs from the antennae and proprioceptive feedback
      from the ipsilateral but not the contralateral forelimb. Locusts also compensated
      for the loss of inputs to one eye by altering their stepping pattern. Changing
      the rung position after initiation of a step showed that targeting of the front
      leg depends on visual information acquired before but not during a step. The
      trajectory was only modified after missing the rung. Our data show that locusts
      walking in environments where footholds are limited use visual and mechanosensory
      information to place their front legs.

PMID- 20036540
TI  - The shaping of male courtship posture by lateralized gustatory inputs to male
      specific interneurons.
AB  - BACKGROUND: Unilateral wing vibration to generate "love songs" is a hallmark of
      male courtship posture in Drosophila melanogaster. In contrast, males of some
      other Drosophila species extend both wings simultaneously during courtship. Thus,
      the patterns of wing movement vary among species and are under stringent genetic
      control, although there are few variations among individuals within a single
      species. These observations prompted the postulation that the proper wing display
      by courting males of D. melanogaster does not require sensory inputs. RESULTS:
      Here we show that when males of D. melanogaster are deprived of gustatory inputs
      mediated by the sensory neurons expressing the taste receptor gene Gr32a, a close
      relative to the pheromone receptor gene Gr68a, they often fail to perform
      unilateral wing extension during courtship because they become unable to keep a
      wing in the resting position while extending another wing. The tarsal amputation
      of a foreleg, but not other legs, increased the occurrence of simultaneous wing
      extension, indicating that Gr32a-expressing cells in this structure are involved
      in the regulation of courting posture. A similar simultaneous wing extension was
      also observed in males in which the putative pheromone-binding protein gene
      Obp57d was inactivated. The axons of Gr32a-expressing cells project to the
      subesophageal ganglion, where their terminals unilaterally contact mAL, which are
      male-specific fruitless (fru)-expressing interneurons that have bilateral
      branches. CONCLUSIONS: Our observations strongly suggest that gustatory pheromone
      inputs ensure the correct laterality of wing vibration that conforms to the
      species-specific behavioral pattern.

PMID- 20036541
TI  - The transcription elongation factor NusA is required for stress-induced
      mutagenesis in Escherichia coli.
AB  - Stress-induced mutagenesis describes the accumulation of mutations that occur in
      nongrowing cells, in contrast to mutagenesis that occurs in actively dividing
      populations, and has been referred to as stationary-phase or adaptive
      mutagenesis. The most widely studied system for stress-induced mutagenesis
      involves monitoring the appearance of Lac(+) revertants of the strain FC40 under
      starvation conditions in Escherichia coli. The SOS-inducible translesion DNA
      polymerase DinB plays an important role in this phenomenon. Loss of DinB (DNA pol
      IV) function results in a severe reduction of Lac(+) revertants. We previously
      reported that NusA, an essential component of elongating RNA polymerases,
      interacts with DinB. Here we report our unexpected observation that wild-type
      NusA function is required for stress-induced mutagenesis. We present evidence
      that this effect is unlikely to be due to defects in transcription of lac genes
      but rather is due to an inability to adapt and mutate in response to
      environmental stress. Furthermore, we extended our analysis to the formation of
      stress-induced mutants in response to antibiotic treatment, observing the same
      striking abolition of mutagenesis under entirely different conditions. Our
      results are the first to implicate NusA as a crucial participant in the
      phenomenon of stress-induced mutagenesis.

PMID- 20036542
TI  - Multicultural family members' experiences with nurses and the intensive care
      context: a hermeneutic study.
AB  - BACKGROUND: The aim of this study was to illuminate the experiences of
      multicultural family members in intensive care units in hospitals, when a loved
      one was critically ill. An increasing migration from non-Western countries to
      Norway and potential double-stress for multicultural families experiencing
      critical illness are pre-understandings. METHODS: The study utilised a Gadamerian
      hermeneutic design. Data were collected through in-depth-interviews (n=5) and
      interpreted, inspired by Lindseth and Norberg's phenomenological hermeneutical
      method. FINDINGS: Multicultural family members' experiences of their encounters
      with nurses were understood as: 'Struggling to preserve the families' cultural
      belonging within the health care system', based on four themes: (a) filtering
      information to reduce concern; (b) understanding and being understood; (c)
      protecting cultural traditions and (d) interaction between roles, rules and
      expectations. CONCLUSION: Family members with a non-Western ethnic background
      experienced several challenges within the complex ICU environment. Multicultural
      family members had distinct strategies to deal with the hospitalisation of a
      critically ill loved one. Interaction difficulties and cultural traditions were
      not influenced by the environment alone, however the challenges seemed to deal
      with universal human interaction independent of the context. Nurses need to be
      sensitive to the families' cultural customs in order to meet their expectations
      in a respectful way.

PMID- 20036543
TI  - Serial evaluation of SOFA score in a Brazilian teaching hospital.
AB  - OBJECTIVES: To evaluate the application of the Sequential Organ Failure
      Assessment (SOFA) in describing the severity of organ dysfunctions and the
      associated mortality rates in critically ill patients at a teaching hospital.
      RESEARCH METHODOLOGY: Prospective longitudinal study performed in 1164 adult,
      critically ill patients who were admitted consecutively into intensive care units
      between January 2004 and December 2005. We analysed static evaluation of SOFA and
      dynamic changes in the SOFA scores. The discriminative power of SOFA was
      evaluated using ROC curves. RESULTS: There was an increase in the mortality rate
      when the SOFA scores increased (chi2(trend)=272.08, p<0.001, increase rate=0.13).
      The SOFA score on the third day in the ICU had the highest area under the curve
      for hospital mortality (AUC: 0.817+/-0.0133, CI 95%: 0.792-0.840). We analysed
      SOFA score changes with time and observed that patients with low scores (0-5)
      upon admission and who increased to the medium or high SOFA groups had a
      significantly higher mortality rate (51.7 and 100%, respectively, p<0.001).
      CONCLUSIONS: Applying SOFA to critically ill patients effectively described the
      severity of organ dysfunctions, and higher SOFA scores had a positive association
      with mortality.

PMID- 20036544
TI  - Ependymal cyst in the conus medullaris.
AB  - The immunohistological features and surgical treatment of an intramedullary
      ependymal cyst in the conus medullaris is presented. An intramedullary ependymal
      cyst is a rare lesion of dysembryoplastic origin. There have been only seven
      patients reported with pathologically proven ependymal cysts in the conus
      medullaris. A 64-year-old woman reported pain and numbness in both thighs and
      feet. Neither sensory nor motor impairment was present in the lower extremities.
      MRI revealed a cyst on the right side of the conus medullaris, compressing the
      spinal cord upward. Clinical signs and symptoms disappeared following surgical
      resection of the cyst. Histological examination showed that this cyst was lined
      with a single layer of tall columnar or low cuboidal cells on fibrous connective
      tissue. The basement membrane was absent in the cyst wall. Reactivity to CAM5.2
      and AE1/AE3 anti-keratin antibodies suggested that the cyst was of
      neuroepithelial origin. No recurrence has been noted 3 years after surgery.

PMID- 20036545
TI  - Metastasis of malignant struma ovarii to the lumbar spine.
AB  - A 32-year-old woman with a solitary metastasis to the lumbar spine from a struma
      ovarii was treated surgically with tumour extirpation and anterior spinal
      reconstruction. Metastasis may occur when a patient has had prior surgery to
      remove this rare tumour.

PMID- 20036546
TI  - Diffuse neuronal perikaryal amyloid precursor protein immunoreactivity in an
      ovine model of non-accidental head injury (the shaken baby syndrome).
AB  - Non-accidental head injury ("shaken baby syndrome") is a major cause of death and
      disability in infants and young children, but it is uncertain whether shaking
      alone is sufficient to cause brain damage or an additional head impact is
      required. Accordingly, we used manual shaking in an ovine model in an attempt to
      answer this question since lambs have a relatively large gyrencephalic brain and
      weak neck muscles resembling a human infant. Neuronal perikaryal and axonal
      reactions were quantified 6 hours after shaking using amyloid precursor protein
      (APP) immunohistochemistry. Neuronal perikaryal APP was widely distributed in the
      brain and spinal cord, the first time such a diffuse neuronal stress response
      after shaking has been demonstrated, but axonal immunoreactivity was minimal and
      largely confined to the rostral cervical spinal cord at the site of maximal
      loading. No ischaemic-hypoxic damage was found in haematoxylin and eosin-stained
      sections.

PMID- 20036547
TI  - Seeding metastases of a benign intraventricular meningioma along the surgical
      track.
AB  - Seeding metastases of a benign intraventricular meningioma along the surgical
      track is rare. We report a patient with a benign fibroblastic intraventricular
      meningioma that had spread along the path of previous surgery; the recurrences as
      well as the primary tumor were benign.

PMID- 20036548
TI  - An intradural-extramedullary gas-forming spinal abscess in a patient with
      diabetes mellitus.
AB  - Spinal infections are commonly reported to be located in the extradural or
      intramedullary spaces. Infection involving the intradural-extramedullary space
      are uncommon. We report a patient with uncontrolled diabetes mellitus and an
      infected foot ulcer who presented with a cervical cord abscess and intradural
      gas. Early diagnosis and aggressive treatment are necessary for a favourable
      outcome in gas-forming intradural spinal abscesses. To our knowledge, a gas
      forming intradural spinal abscess has not been reported previously and we discuss
      the relevant literature.

PMID- 20036549
TI  - Cerebral oxygen metabolism and neuroelectrophysiology in a clinical study of
      severe brain injury and mild hypothermia.
AB  - Mild hypothermia has an important role in the treatment of severe brain injury
      and there are therapeutic windows for this technique for patients with severe
      brain injury. We used a randomized, controlled, clinical study to investigate
      indexes of cerebral oxygen metabolism and neuroelectrophysiology to evaluate the
      efficacy of mild hypothermia treatment in severe brain injury. A total of 148
      patients (106 males and 42 females), aged 18 to 64 years with acute severe brain
      injury were selected from June 1998 to June 2004 from the Department of
      Neurosurgery at The First Affiliated Hospital of Chongqing Medical University.
      All patients met the inclusion criteria: admission to hospital within 10 hours of
      injury; Glasgow Coma Scale (GCS) score 8; age < 65 years; no other severe
      combined visceral injury; and no severe co-morbidities of the heart, lung, liver,
      kidney, or other visceral organs. Patients were divided into groups according to
      brain injury severity: GCS scores 7-8, 5-6, and 3-4. Patients in each GCS score
      group were randomly assigned to two subgroups: hypothermia and normothermia.
      Brain oxygen metabolism indexes (partial pressure of oxygen in brain tissue
      [P(br)O(2)] and regional cerebral oxygen saturation [rSaO(2)]) as well as
      neuroelectrophysiology indexes (short-latency somatosensory evoked potential
      [SLSEP] and brain-stem auditory evoked potential [BAEP]) were recorded in the
      normothermia and hypothermia subgroups (32-34 degrees C) prior to and after
      cooling for 5 days. Brain oxygen metabolism indexes (P(br)O(2) and rSaO(2)) and
      neuroelectrophysiology indexes (SLSEP and BAEP) were also compared for patients
      who underwent mild hypothermia and those who did not. For patients with GCS 7-8,
      SLSEP, BAEP and rSaO(2) following cooling were significantly improved in the
      hypothermia subgroup and the P(br)O(2) was less in the hypothermia subgroup. For
      patients with GCS 5-6, the SLSEP, BAEP and rSaO(2) were improved following
      hypothermia on some days, and the PbrO(2) was greater in the hypothermia subgroup
      on some days. For patients with GCS 3-4, there was no difference between the
      hypothermia and normothermia subgroups. We conclude that hypothermia had a
      significant therapeutic effect on severe brain injury of patients with GCS 7-8,
      had no effect on patients with GCS 3-4, and an uncertain effect on patients with
      GCS 5-6. The indexes of cerebral oxygen metabolism and neuroelectrophysiology
      indicated primary and secondary brain injury, respectively, and provided an
      effective way to evaluate brain injury.

PMID- 20036550
TI  - Intracavernous sinus arachnoid cyst with optic neuropathy.
AB  - An 18-year-old man experienced progressive decreased visual acuity associated
      with a redness of the right eye for 1 month. An arachnoid cyst was identified
      within the right cavernous sinus and fenestration to the basal cistern was
      performed with the aid of a neuroendoscope. Visual acuity improved dramatically
      after the operation. Intracavernous sinus arachnoid cyst is a rare congenital
      intracranial lesion and surgical decompression may benefit symptomatic patients.

PMID- 20036551
TI  - Postural tremor as a manifestation of spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is a syndrome caused by low
      cerebrospinal fluid (CSF) pressure due to leakage of CSF. Clinically, orthostatic
      headache, neck pain, nausea, emesis, interscapular pain, diplopia, dizziness,
      changes in hearing, visual blurring and radicular upper extremity symptoms are
      most frequently observed. We describe a 57-year-old man with SIH who presented
      with postural tremor. CSF leakage was revealed by cranial MRI. Lumbar puncture
      identified low CSF pressure and intrathecal gadolinium enhanced MR cisternography
      showed diffuse CSF leakage in the thoracolumbar region. The patient underwent
      epidural blood patching, which resulted in complete resolution of postural tremor
      within 2 months.

PMID- 20036552
TI  - An unusual primitive neuroectodermal tumor in the thoracic epidural space.
AB  - Primitive neuroectodermal tumor (PNET) is a generic term used to describe a group
      of histologically indistinguishable neoplasms, including cerebellar
      medulloblastomas, which are located at various sites in the central nervous
      system. Primary epidural PNETs are rare and few patients have been reported. We
      report a 15-year-old girl who presented with gradual onset, over 1 month, of
      upper back pain and bilateral lower leg weakness. A thoracic spine MRI showed a
      dumbbell-shaped epidural mass at T2-4 with right paraspinal and posterior
      mediastinal extension. Surgical resection of the epidural tumor for decompression
      was performed. The pathologic examination revealed a PNET. Primary spinal PNETs
      typically have a poor prognosis and optimal therapy has not yet been defined.
      Surgical resection, with the combination of chemo-radiotherapy or radiotherapy,
      leads to better outcomes. However, primary epidural PNETs may be classified as a
      subtype of spinal PNETs because they are free from intrathecal invasion. For
      these patients, surgery alone and surgery combined with radiotherapy or chemo
      radiotherapy remain controversial. Our patient received surgery alone and, 1y ear
      later, has experienced no local recurrence within the epidural space but the
      mediastinal part of the tumor has enlarged.

PMID- 20036553
TI  - Peripheral Primitive Neuroectodermal Tumour (pPNET) in the cervical spine.
AB  - Primary spinal primitive neuroectodermal tumours are rare. We present a 45-year
      old man with a peripheral primitive neuroectodermal tumour arising in the
      cervical spine. We believe this to be the first report of this type of tumour in
      the cervical spine.

PMID- 20036554
TI  - Expressions of angiogenesis associated matrix metalloproteinases and
      extracellular matrix proteins in cerebral vascular malformations.
AB  - This study aimed to compare cerebral arteriovenous malformations (cAVM) and
      cerebral cavernous malformations (CCM) with regard to the immunohistochemical
      expressions of matrix metalloproteinases (MMP) and selected extracellular matrix
      (ECM) proteins, which have a role in the regulation of angiogenesis. Fresh-frozen
      surgical specimens from patients with cAVM (n=14) and CCM (n=15) were
      immunohistochemically stained with antibodies for MMP-2, MMP-9, laminin,
      fibronectin and tenascin. To compare cAVM and CCM, expression of each protein was
      graded using a four-point scoring system for each histological layer of the
      lesion. MMP-2 and MMP-9 were more strongly expressed in the vascular walls of
      CCMs compared to cAVMs for all comparable layers: endothelium, subendothelium and
      the perivascular space. The stronger expression of MMP and other EMP associated
      with early angiogenesis in CCMs compared to AVMs may support the hypothesis that
      CCMs occur at earlier embryogenic stages than AVMs.

PMID- 20036555
TI  - Clinical features and management of five patients with supratentorial
      subependymoma.
AB  - Subependymoma is a rare low-grade glioma of the central nervous system that is
      often asymptomatic and discovered incidentally. If symptomatic, however, its
      clinical features vary widely. We report and discuss the management of five
      surgical patients (two males and three females, 27-65 years old). All tumors
      developed supratentorially around the foramen of Monro, and their diameters
      ranged from 18 mm to 90 mm. Of the three symptomatic patients, one presented with
      sudden loss of consciousness despite having only a small tumor, while in
      contrast, another patient showed only gradual memory disturbance despite having a
      very large tumor (90 mm diameter). Two patients were asymptomatic but had
      ventricular dilatation. Gross total resection was achieved via either a
      transcortical (three patients) or an anterior transcallosal approach (two
      patients). No recurrence was observed during follow-up. We concluded that as
      surgery is the only curative treatment for subependymoma, and even a small tumor
      can present with sudden deterioration, we recommend early and total resection.

PMID- 20036557
TI  - Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque
      in the brain.
AB  - A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in
      this study for potential use as beta-amyloid (Abeta) plaque probes. Staining of
      hippocampus tissue sections from Alzheimer's disease (AD) brain with the
      representative compound 9 indicated selective labeling of it to Abeta plaques.
      The binding affinity of radioiodinated [(125)I]9 for AD brain homogenates was
      0.21 nM (K(d)), and of other derivatives ranged from 0.9 to 19.7 nM, except for N
      methyl-4,5-dianilinophthalimide (K(i)>1000 nM). [(125)I]9 possessed the optimal
      lipophilicity with LogP value of 2.16, and its in vivo biodistribution in normal
      mice exhibited excellent initial brain uptake (5.16% ID/g at 2 min after
      injection) and a fast washout rate (0.56% ID/g at 60 min). The encouraging
      results suggest that this novel derivative of [(123)I]9 may have potential as an
      in vivo SPECT probe for detecting amyloid plaques in the brain.

PMID- 20036556
TI  - Alzheimer's disease: insights from Drosophila melanogaster models.
AB  - The power of fruit fly genetics is being deployed against some of the most
      intractable and economically significant problems in modern medicine, the
      neurodegenerative diseases. Fly models of Alzheimer's disease can be exposed to
      the rich diversity of biological techniques that are available to the community
      and are providing new insights into disease mechanisms, and assisting in the
      identification of novel targets for therapy. Similar approaches might also help
      us to interpret the results of genome-wide association studies of human
      neurodegenerative diseases by allowing us to triage gene "hits" according to
      whether a candidate risk factor gene has a modifying effect on the disease
      phenotypes in fly model systems.

PMID- 20036558
TI  - Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag.
AB  - Artificial insulin with an N-linked oligosaccharide was synthesized by a chemo
      enzymatic method using endo-beta-N-acetylglucosaminidase from Mucor hiemalis
      (Endo-M). GlcNAc-modified insulin was prepared by the reaction of the
      carboxymethyl glycoside of GlcNAc and 3 amino groups of bovine insulin using a
      dimethylphosphinothioic mixed anhydride (Mpt-MA) method. A transglycosylation
      reaction of the GlcNAc-modified insulin using Endo-M gave mono-transglycosylated
      insulin predominantly. We determined the transglycosylation site of the mono
      transglycosylated insulin.

PMID- 20036559
TI  - Triazoloacridin-6-ones as novel inhibitors of the quinone oxidoreductases NQO1
      and NQO2.
AB  - A range of triazoloacridin-6-ones functionalized at C5 and C8 have been
      synthesized and evaluated for ability to inhibit NQO1 and NQO2. The compounds
      were computationally docked into the active site of NQO1 and NQO2, and calculated
      binding affinities were compared with IC(50) values for enzyme inhibition.
      Excellent correlation coefficients were demonstrated suggesting a predictive QSAR
      model for this series of structurally similar analogues. From this we have
      identified some of these triazoloacridin-6-ones to be the most potent NQO2
      inhibitors so far reported.

PMID- 20036560
TI  - Fluoroalkene modification of mercaptoacetamide-based histone deacetylase
      inhibitors.
AB  - Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of
      anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be
      less toxic than hydroxamate and are worthy of further consideration. Therefore,
      we have designed a series of analogs as potential inhibitors of HDACs, in which
      the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and
      their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was
      observed for all synthetic compounds.

PMID- 20036561
TI  - Comparative molecular field analysis of fenoterol derivatives: A platform towards
      highly selective and effective beta(2)-adrenergic receptor agonists.
AB  - PURPOSE: To use a previously developed CoMFA model to design a series of new
      structures of high selectivity and efficacy towards the beta(2)-adrenergic
      receptor. RESULTS: Out of 21 computationally designed structures 6 compounds were
      synthesized and characterized for beta(2)-AR binding affinities, subtype
      selectivities and functional activities. CONCLUSION: the best compound is (R,R)-4
      methoxy-1-naphthylfelnoterol with K(i)beta(2)-AR=0.28microm, K(i)beta(1)
      AR/K(i)beta(2)-AR=573, EC(50cAMP)=3.9nm, EC(50cardio)=16nm. The CoMFA model
      appears to be an effective predictor of the cardiomocyte contractility of the
      studied compounds which are targeted for use in congestive heart failure.

PMID- 20036563
TI  - Synthesis and biological properties of iron chelators based on a bis-2-(2-hydroxy
      phenyl)-thiazole-4-carboxamide or -thiocarboxamide (BHPTC) scaffold.
AB  - Bis-2-(2-hydroxy-phenyl)-thiazole-4-carboxamides and -thiocarboxamides (BHPTCs)
      form a family of gemini hexacoordinated bis-tridentate chelating scaffolds. Four
      molecules were synthesized and shown to chelate iron(III) efficiently with a 1:1
      stoichiometry. A dithioamide BHPTC displayed promising antiproliferative activity
      in several cancerous cell lines, making this molecule an interesting lead
      compound for the design of new iron-chelating anticancer drugs. Conversely,
      diamide BHPTCs had significant cytoprotective activity against iron overload in
      HepaRG cells in vitro, and were as efficient as and less toxic than deferoxamine
      B (DFO).

PMID- 20036562
TI  - 2-Dialkynyl derivatives of (N)-methanocarba nucleosides: 'Clickable' A(3)
      adenosine receptor-selective agonists.
AB  - We modified a series of (N)-methanocarba nucleoside 5'-uronamides to contain
      dialkyne groups on an extended adenine C2 substituent, as synthetic intermediates
      leading to potent and selective A(3) adenosine receptor (AR) agonists. The
      proximal alkyne was intended to promote receptor recognition, and the distal
      alkyne reacted with azides to form triazole derivatives (click cycloaddition).
      Click chemistry was utilized to couple an octadiynyl A(3)AR agonist to azido
      containing fluorescent, chemically reactive, biotinylated, and other moieties
      with retention of selective binding to the A(3)AR. A bifunctional thiol-reactive
      crosslinking reagent was introduced. The most potent and selective novel compound
      was a 1-adamantyl derivative (K(i) 6.5nM), although some of the click products
      had K(i) values in the range of 200-400nM. Other potent, selective derivatives
      (K(i) at A(3)AR innM) were intended as possible receptor affinity labels: 3-nitro
      4-fluorophenyl (10.6), alpha-bromophenacyl (9.6), thiol-reactive isothiazolone
      (102), and arylisothiocyanate (37.5) derivatives. The maximal functional effects
      in inhibition of forskolin-stimulated cAMP were measured, indicating that this
      class of click adducts varied from partial to full A(3)AR agonist compared to
      other widely used agonists. Thus, this strategy provides a general chemical
      approach to linking potent and selective A(3)AR agonists to reporter groups of
      diverse structure and to carrier moieties.

PMID- 20036565
TI  - Antifolate and antiproliferative activity of 6,8,10-triazaspiro[4.5]deca-6,8
      dienes and 1,3,5-triazaspiro[5.5]undeca-1,3-dienes.
AB  - Two series of triazaspiroalkanedienes, bearing a substituted phenoxy propyloxy
      side chain, were identified as potent mammalian DHFR inhibitors. One series has a
      6,5-spiro bicyclic ring system and the other series has a 6,6-spiro bicyclic
      system. Both series were synthesized and tested for in vitro mammalian DHFR
      inhibitory activity and antiproliferative activity against A549 human lung-cancer
      cells. Compound 3c showed the highest antiproliferative activity against A549
      cells with an IC(50) value of 27.1nM. Rescue experiment confirmed its antifolate
      antiproliferative mechanism. The excellent antifolate and antiproliferative
      activity of selected analogues presented in this study warrants further
      investigation as potential leads in the anticancer drug discovery.

PMID- 20036564
TI  - Towards the synthesis of bisubstrate inhibitors of protein farnesyltransferase:
      Synthesis and biological evaluation of new farnesylpyrophosphate analogues.
AB  - Protein farnesyltransferase (FTase) has recently appeared as a new target of
      parasitic diseases, a field poor in drugs in development. With the aim of
      creating new bisubstrate inhibitors of FTase, new farnesyl pyrophosphate
      analogues have been studied. Farnesyl analogues with a malonic acid function
      exhibited the best inhibitory activity on FTase. This group was introduced into
      our imidazole-containing model leading to new compounds with submicromolar
      activities. Kinetic experiments have been realized to determine their binding
      mode to the enzyme.

PMID- 20036566
TI  - Apoptotic activities in closely related styryllactone stereoisomers toward human
      tumor cell lines: Investigation of synergism of styryllactone-induced apoptosis
      with TRAIL.
AB  - A related series of styryllactones with small functional and stereochemical
      variations were compiled for a comparative study of their apoptotic activities
      toward two tumorigenic and one non-tumorigenic control cell line. While a
      substantial range of intrinsic activity was observed, the relative order of
      activity of the different compounds toward the cell types varied somewhat as did
      the relative ratios of apoptosis and necrosis observed in conjunction with the
      loss of cell viability. While some of the styryllactones showed substantial
      activity, a small but significant apoptosis-induced synergism was demonstrated
      with (-)-altholactone and TRAIL (tumor necrosis factor-related apoptosis-inducing
      ligand).

PMID- 20036567
TI  - First measurement of the beta spectrum of 241Pu with a cryogenic detector.
AB  - The LNE-LNHB is developing metallic magnetic calorimeters, a specific type of
      cryogenic detectors, for beta spectrometry. The aim is the determination of the
      shape factors of beta spectra. Our latest detector has been designed to measure
      the spectrum of (241)Pu, a pure beta emitter with an endpoint energy of 20.8 keV.
      In this paper, the detection principle of metallic magnetic calorimeters is
      explained and a detailed description is given of the realization of the detector
      enclosing a (241)Pu source inside the detector absorber. A spectrum resulting
      from our first measurement is shown and compared with a theoretical spectrum.

PMID- 20036568
TI  - Radiation formation of colloidal silver particles in aqueous systems.
AB  - This paper reports on the formation of silver nanoparticles initiated by gamma
      and UV radiation in various aqueous solutions. Inorganic precursors were used for
      radiation and/or photochemical reduction of Ag(+) ions to a metallic form. The
      influence of various parameters on the nucleation and formation of colloid
      particles was studied. Attention was also focused on the composition of the
      irradiated solution. Aliphatic alcohols were used as scavengers of OH radicals
      and other oxidizing species. The influence of the stabilizers on the formation
      and stability of the nanoparticles was studied.

PMID- 20036569
TI  - Tests of nuclear half-lives as a function of the host medium and temperature:
      refutation of recent claims.
AB  - When radioactive isotopes that decay by alpha, beta(-), beta(+) and electron
      capture transitions are placed in a conducting host material, it has recently
      been claimed that their half-lives show a significant dependence on temperature
      up to a 6% difference between room temperature and 12K. We have refuted two of
      these claims by measuring: (1) the beta(-) decay of (198)Au in gold, for which we
      find the half life to be the same within 0.04% between room temperature and 19K;
      and (2) the electron-capture decay of (97)Ru in ruthenium, for which we find any
      half-life difference to be <0.1%.

PMID- 20036570
TI  - The half-life of 18F.
AB  - The half-life of the positron-emitter (18)F has been measured by following the
      decay rate with three systems: ionization chambers, Ge detectors and coincidence
      with fast scintillators. The decay rate was measured for periods of time up to 9
      half-lives. The combination of the results obtained with the three measuring
      systems gives a value of T(1/2)=1.82871 (18)h, in good agreement with recommended
      data and with an estimated uncertainty lower than any other previously reported
      value.

PMID- 20036571
TI  - Sensitivity and uncertainty analysis of the simulation of 123I and 54Mn gamma and
      X-ray emissions in a liquid scintillation vial.
AB  - Radiation transport simulations of the most probable gamma- and X-ray emissions
      of (123)I and (54)Mn in a three photomultiplier tube liquid scintillation
      detector have been carried out. A Geant4 simulation was used to acquire energy
      deposition spectra and interaction probabilities with the scintillant, as
      required for absolute activity measurement using the triple to double coincidence
      ratio (TDCR) method. A sensitivity and uncertainty analysis of the simulation
      model is presented here. The uncertainty in the Monte Carlo simulation results
      due to the input parameter uncertainties was found to be more significant than
      the statistical uncertainty component for a typical number of simulated decay
      events. The model was most sensitive to changes in the volume of the scintillant.
      Estimates of the relative uncertainty associated with the simulation outputs due
      to the combined stochastic and input uncertainties are provided. A Monte Carlo
      uncertainty analysis of an (123)I TDCR measurement indicated that accounting for
      the simulation uncertainties increases the uncertainty of efficiency of the
      logical sum of double coincidence by 5.1%.

PMID- 20036572
TI  - Contouring the forehead and rhinoplasty in the feminization of the face in male
      to-female transsexuals.
AB  - Transsexualism is a gender identity disorder in which there is a strong and
      ongoing desire to live and be accepted as a member of the opposite sex. In male
      to-female transsexuals with strong masculine facial features facial feminization
      surgery can be performed as part of gender reassignment. The male forehead has
      extensive supraorbital bossing, and above this there is often a flat area before
      the convex curvature of the upper forehead begins. In the female, the
      supraorbital bossing is considerably less, often nonexistent, and above this the
      flattening is usually less marked and more of a continuous mild curvature. The
      female nose is relatively smaller than the male nose. The glabellar and the
      nasolabial angle are less acute. The female nose is regarded as attractive if it
      shows a straight or mildly concave dorsum and an accented tip. We present a case
      of treatment of a 26-year-old male-to-female transsexual to demonstrate that
      contouring the forehead combined with a rhinoplasty can lead to significant
      feminization of the face. The procedures described seem to be safe and reliable.

PMID- 20036574
TI  - Cancer patients with cardiovascular disease have survival rates comparable to
      cancer patients within the age-cohort of 10 years older without cardiovascular
      morbidity.
AB  - Due to aging of the population the prevalence of both cardiovascular diseases
      (CVDs) and cancer is increasing. Elderly patients are often under-represented in
      clinical trials, resulting in limited guidance about treatment and outcome. This
      study gives insight into the prevalence of CVD among unselected patients with
      colon, rectum, lung, breast and prostate cancer and its effects on cancer
      treatment and outcome. Over one fourth (N=11,200) of all included cancer patients
      aged 50 or older (N=41,126) also suffered from CVD, especially those with lung
      (34%) or colon cancer (30%). These patients were often treated less aggressively,
      especially in case COPD or diabetes was also present. CVD had an independent
      prognostic effect among patients with colon, rectum and prostate cancer. This
      prognostic effect could not be fully explained by differences in treatment.
      CONCLUSIONS: Many cancer patients with severe CVD have a poorer prognosis. More
      research is needed for explaining the underlying factors for the decreased
      survival. Such research should lead to treatment guidelines for these patients.

PMID- 20036575
TI  - Thr-114 is an important functional residue of fibroblast growth factor 10
      identified by structure-based mutational analysis.
AB  - Fibroblast growth factor 10 (FGF10) plays important roles in vertebrate limb
      development, lung branching morphogenesis, and epidermis regeneration. The
      receptor (FGFR2b) binding specificity is an essential element in regulating the
      diverse functions of FGF10. Analyzing the FGF10:FGFR2b complex we found that Thr
      114 in beta4 of FGF10 could form specific interactions with D3 of FGFR2b. To
      investigate the role of Thr-114 played on functions of FGF10, two mutants of
      FGF10 were constructed, named TA (Thr-114-->Ala) and TR (Thr-114-->Arg),
      respectively. The biological activity assays showed that the receptor-binding
      affinity, the stimulating growth effect on rat tracheal epithelium (RTE) cells,
      and the inducing ability in receptor phosphorylation of both mutants were
      decreased, which were consistent with the interaction analysis of the TA:FGFR2b
      and TR:FGFR2b complexes. These results suggested that Thr-114 is a crucial
      functional residue for FGF10, and mutating Thr-114 to Ala or Arg would lead to
      great decrease in receptor-binding affinity and biological activity of FGF10.

PMID- 20036573
TI  - Aortic valve replacement for active infective endocarditis: 5-year survival
      comparison of bioprostheses, homografts and mechanical prostheses.
AB  - OBJECTIVE: In the surgical treatment of acute aortic valve infective endocarditis
      (IE), the long-term outcome depending on the choice of valve replacement remains
      uncertain. We aimed to compare the impact on 5-year mortality of use of three
      types of implanted valves: bioprosthesis (heterograft), mechanical prosthesis and
      homograft. METHODS: A total of 167 patients with a definite aortic valve IE who
      underwent aortic replacement were selected from a prospective observational
      population-based study. Association between the type of implanted valve and 5
      year mortality was examined by the use of an adjusted Cox model. RESULTS:
      Bioprostheses were implanted in 31 patients (18.6%), homograft in 27 (16.2%) and
      mechanical valves in 109 (65.2%). Patients with bioprothesis had a higher 5-year
      mortality risk than patients with mechanical prosthesis (adjusted hazard ratio
      (HR) 2.39, 95% confidence interval (95% CI), 1.09-5.21; p=0.029), particularly in
      patients < or =65 years old (adjusted HR 4.14 (1.27-13.45), p=0.018) but not in
      patients >65 years old (adjusted HR: 1.45 (0.35-5.97), p=0.60). Five-year
      mortality risk did not differ between patients with homografts and those with
      mechanical prostheses (HR 0.46, 95% CI (0.15-1.42), p=0.18). CONCLUSIONS: A
      bioprosthetic valve used for aortic valve IE replacement may be associated with
      lower overall 5-year survival than the use of a mechanical valve in patients up
      to 65 years old. Further studies are needed to explain these results.

PMID- 20036576
TI  - Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord
      blood and its relation to perinatal clinical findings.
AB  - Few papers have investigated the cytokine profiles of multiple cytokines in cord
      blood. We obtained cord blood samples from 224 infants admitted to our neonatal
      intensive care unit. Cytokine profiles of 17 cytokines were investigated using
      cytometric bead array technology. We found a wide variety of cytokines of various
      levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in
      macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly
      correlated with each other and with granulocyte-colony stimulating factor and IL
      8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant
      correlation with other cytokines. Several maternal factors were strongly related
      to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1
      were closely related to certain neonatal diseases in preterm neonates. Some
      cytokines may be regulated independently of each other, while others appear to
      work as a network affecting physiological and pathological conditions in the
      fetus.

PMID- 20036578
TI  - Subsequent autoimmune or related disease in asthma patients: clustering of
      diseases or medical care?
AB  - PURPOSE: Asthma includes immunological components that may share mechanisms with
      autoimmune diseases. We analyzed the subsequent occurrence of any of 22
      autoimmune and related conditions in hospitalized asthma patients. METHODS: A
      nationwide study was conducted in Sweden on subsequent diseases of asthma
      patients on the basis of the Hospital Discharge Register. Standardized incidence
      ratios (SIRs) were calculated for subsequent autoimmune diseases. RESULTS: A
      total of 4006 patients were hospitalized for an autoimmune condition after last
      hospitalization for asthma. The SIRs were increased for 11 subsequent autoimmune
      conditions, diagnosed at least 5 years after asthma. The highest SIRs were noted
      for polyarteritis nodosa (4.29) and Addison disease (3.62). SIRs for these
      diseases and others, including the most common autoimmune disease rheumatoid
      arthritis, were increased even when the follow-up was started 5 years after the
      last asthma hospitalization. Addison disease and Crohn disease were increased in
      asthma patients hospitalized at various ages, whereas young asthma patients
      presented with celiac disease and immune thrombocytopenic purpura. CONCLUSIONS:
      Hospitalized asthma patients presented with a number of subsequent autoimmune and
      related diseases. Although we were unable to exclude the effects of environmental
      factors, the data suggest that shared genetic factors or gene-environment
      interactions may explain coexistence of some of these diseases.

PMID- 20036577
TI  - Gene modulation and immunoregulatory roles of interferon gamma.
AB  - Interferon-gamma (IFNgamma) is a central regulator of the immune response and
      signals via the Janus Activated Kinase (JAK)-Signal Transducer and Activator of
      Transcription (STAT) pathway. Phosphorylated STAT1 homodimers translocate to the
      nucleus, bind to Gamma Activating Sequence (GAS) and recruit additional factors
      to modulate gene expression. A bioinformatics analysis revealed that greater
      number of putative promoters of immune related genes and also those not directly
      involved in immunity contain GAS compared to response elements (RE) for
      Interferon Regulatory Factor (IRF)1, Nuclear factor kappa B (NFkappaB) and
      Activator Protein (AP)1. GAS is present in putative promoters of well known
      IFNgamma-induced genes, IRF1, GBP1, CXCL10, and other genes identified were TLR3,
      VCAM1, CASP4, etc. Analysis of three microarray studies revealed that the
      expression of a subset of only GAS containing immune genes were modulated by
      IFNgamma. As a significant correlation exists between GAS containing immune genes
      and IFNgamma-regulated gene expression, this strategy may identify novel IFNgamma
      responsive immune genes. This analysis is integrated with the literature on the
      roles of IFNgamma in mediating a plethora of functions: anti-microbial responses,
      antigen processing, inflammation, growth suppression, cell death, tumor immunity
      and autoimmunity. Overall, this review summarizes our present knowledge on
      IFNgamma mediated signaling and functions.

PMID- 20036579
TI  - Surgical treatment of complex distal humeral fractures: functional outcome after
      internal fixation using precontoured anatomic plates.
AB  - HYPOTHESIS: Several studies have shown good results with internal fixation of
      distal humeral fractures; however, few have focused specifically on anatomic
      parallel plate fixation using the same implant and postoperative regimen. The
      purpose of this study was to determine the functional outcome after open
      reduction and internal fixation of these complex fractures using parallel
      precontoured anatomic plates. MATERIALS AND METHODS: This was a retrospective
      single-surgeon series involving 16 patients (12 women, 4 men) treated with a
      double-column parallel plating technique. Clinical assessment included the Mayo
      Elbow Performance Score (MEPS) and Disabilities of the Arm, Shoulder and Hand
      Score (DASH). Mean age was 43 years (range, 20-78 years). Average follow-up was
      35 months. Four fractures were AO type A and 12 were AO type C. RESULTS: Union
      was achieved in all patients. There was no superficial or deep infection or
      hardware failure. Two patients required removal of plates for pain and prominence
      but not all screws could be completely removed. The mean flexion was 132 degrees
      and extension was 29 degrees . The mean DASH score was 46.1. Grip strength was
      56% of the uninjured side. Mean flexion and extension force was 72% and 70%,
      respectively, of the uninjured elbow. The mean MEPS score was 72.3. DISCUSSION:
      Anatomically precontoured parallel plates are effective in achieving bony union
      with low implant failure with acceptable functional outcomes. However, screw
      extraction can be difficult when the implant is removed.

PMID- 20036580
TI  - Radiocapitellar joint contacts after bipolar radial head arthroplasty.
AB  - PURPOSE: The purpose of this study was to determine radiocapitellar contacts
      before and after radial head replacement, using the bipolar design of Judet.
      METHODS: Joint contacts were measured by moulding the joint surfaces of 6 fresh
      frozen cadaveric specimens, in various positions of elbow flexion and forearm
      rotation. RESULTS: Expressed as function of the radial cup, contact areas
      averaged 44% in the normal elbow, decreasing with flexion and increasing with
      supination (P < .05). After prosthetic implantation, contact areas averaged 33%
      and remained quite similar, irrespective of elbow position. Subluxation of the
      prosthetic head over the lateral margin of the trochlea was seen systematically
      with supination. CONCLUSIONS: Because of intraprosthetic mobility, contact areas
      were not dependant on elbow position. This adaptability, however, also led to
      abnormal positioning of the prosthetic radial head with supination, subluxing
      over the trochlea lateral margin.

PMID- 20036581
TI  - Regarding "Large coronal shear fractures of the capitellum and trochlea treated
      with headless compression screws".

PMID- 20036582
TI  - Intra-articular osteochondroma of the elbow: a case report.

PMID- 20036583
TI  - Radiographic and histopathologic analysis of osteolysis after total shoulder
      arthroplasty.
AB  - HYPOTHESIS: This study analyzed clinical, radiographic, and histologic data from
      failed total shoulder arthroplasties (TSAs) to determine factors associated with
      osteolysis. MATERIALS AND METHODS: From 1985 to 2005, 52 patients (mean age, 61.6
      years) underwent revision TSA at a single institution at a mean of 4.3 years
      after their index surgery. Patients were retrospectively assigned to 2 cohorts
      based on the presence (n = 10) or absence (n = 42) of osteolysis around their
      implants on the last prerevision surgery radiographs. Clinical information,
      associated histopathology from tissues obtained at revision surgery, and
      polyethylene wear data from the retrieved glenoid components were compared
      between groups. RESULTS: In the osteolysis group, 20% had screw fixation compared
      with 2.5% without osteolysis (P = .039). The radiolucency score was significantly
      higher in the osteolysis group: 12.7 +/- 2.0 vs 8.7 +/- 3.7 (P = .003). Wear
      analysis of the osteolysis group demonstrated significant increases in third-body
      particles compared with those implants without osteolysis (P = .004). Histology
      available from retrieved implants demonstrated particulate debris in 62% of
      patients with osteolytic lesions vs 67% without osteolytic lesions (P > .05).
      DISCUSSION: Significant differences were found in patients with osteolytic
      lesions compared with patients undergoing TSA revision surgery without such
      lesions, specifically with regard to glenoids that used adjuvant screw fixation,
      the presence of increased radiolucent lines, and an abundance of third-body wear.
      No significant differences were found in particulate wear debris despite the
      prevailing notion that osteolysis is associated with particulate debris from
      implant wear. CONCLUSION: Screw fixation and third-body wear were associated with
      osteolysis after TSA.

PMID- 20036584
TI  - Time to diagnosis and performance levels during repeat interpretations of digital
      breast tomosynthesis: preliminary observations.
AB  - RATIONALE AND OBJECTIVES: To compare time to interpretation and diagnostic
      performance levels during repeat readings of full-field digital mammography
      (FFDM) and digital breast tomosynthesis (DBT) in a retrospective study. MATERIALS
      AND METHODS: Three experienced radiologists twice interpreted 125 selected
      examinations, 35 with verified cancers and 90 negative for cancer during a period
      of 22 months using FFDM alone followed by a combined FFDM + DBT mode. Changes in
      time to "review and rate" these examinations as well as in diagnostic performance
      levels where assessed. A fixed-effect analysis accounting for cross-correlation
      due to the review of the same examinations by the same readers was performed.
      RESULTS: The total (combined) time to review and rate an examination increased on
      average by 33% between the first and second readings of the same examinations (P
      < .001). Radiologists reduced their time to review FFDM before making the DBT
      available for viewing. However, they spent more time reviewing the combined FFDM
      + DBT mode. The recall rates for examinations depicting cancer remained largely
      unchanged. Among the groups of examinations with concordant and discordant recall
      recommendations during the two readings only the group examinations that were
      "newly recalled" during repeat reading, took significantly longer (P < .01).
      CONCLUSION: DBT-based breast imaging may ultimately result in a substantial
      increase in performance; however, without efficiency improvements DBT may take
      longer to interpret. Addition of "false-positive recalls" was most strongly
      associated with increase in interpretation time while elimination of "false
      positive recalls" did not require longer interpretation time.

PMID- 20036585
TI  - Short term effects of magnetic resonance imaging on excitability of the motor
      cortex at 1.5T and 7T.
AB  - RATIONALE AND OBJECTIVES: The increasing spread of high-field and ultra-high
      field magnetic resonance imaging (MRI) scanners has encouraged new discussion of
      the safety aspects of MRI. Few studies have been published on possible cognitive
      effects of MRI examinations. The aim of this study was to examine whether changes
      are measurable after MRI examinations at 1.5 and 7 T by means of transcranial
      magnetic stimulation (TMS). MATERIALS AND METHODS: TMS was performed in 12
      healthy, right-handed male volunteers. First the individual motor threshold was
      specified, and then the cortical silent period (SP) was measured. Subsequently,
      the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using
      standard sequences. The MRI examination was immediately followed by another TMS
      session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete
      setting was repeated using a 7-T scanner. Control conditions included lying in
      the 1.5-T scanner for 63 minutes without scanning and lying in a separate room
      for 63 minutes. TMS was performed in the same way in each case. For statistical
      analysis, Wilcoxon's rank test was performed. RESULTS: Immediately after MRI
      exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and
      7 T. The motor threshold was significantly increased. Fifteen minutes after the
      examination, the measured value tended toward normal again. Control conditions
      revealed no significant differences. CONCLUSION: MRI examinations lead to a
      transient and highly significant alteration in cortical excitability. This effect
      does not seem to depend on the strength of the static magnetic field.

PMID- 20036586
TI  - Effect of breast compression on lesion characteristic visibility with diffraction
      enhanced imaging.
AB  - RATIONALE AND OBJECTIVES: Conventional mammography can not distinguish between
      transmitted, scattered, or refracted x-rays, thus requiring breast compression to
      decrease tissue depth and separate overlapping structures. Diffraction-enhanced
      imaging (DEI) uses monochromatic x-rays and perfect crystal diffraction to
      generate images with contrast based on absorption, refraction, or scatter.
      Because DEI possesses inherently superior contrast mechanisms, the current study
      assesses the effect of breast compression on lesion characteristic visibility
      with DEI imaging of breast specimens. MATERIALS AND METHODS: Eleven breast tissue
      specimens, containing a total of 21 regions of interest, were imaged by DEI
      uncompressed, half-compressed, or fully compressed. A fully compressed DEI image
      was displayed on a soft-copy mammography review workstation, next to a DEI image
      acquired with reduced compression, maintaining all other imaging parameters. Five
      breast imaging radiologists scored image quality metrics considering known lesion
      pathology, ranking their findings on a 7-point Likert scale. RESULTS: When fully
      compressed DEI images were compared to those acquired with approximately a 25%
      difference in tissue thickness, there was no difference in scoring of lesion
      feature visibility. For fully compressed DEI images compared to those acquired
      with approximately a 50% difference in tissue thickness, across the five readers,
      there was a difference in scoring of lesion feature visibility. The scores for
      this difference in tissue thickness were significantly different at one rocking
      curve position and for benign lesion characterizations. These results should be
      verified in a larger study because when evaluating the radiologist scores
      overall, we detected a significant difference between the scores reported by the
      five radiologists. CONCLUSIONS: Reducing the need for breast compression might
      increase patient comfort during mammography. Our results suggest that DEI may
      allow a reduction in compression without substantially compromising clinical
      image quality.

PMID- 20036587
TI  - Valvular regurgitations in the horse: the importance of an exercise ECG.

PMID- 20036588
TI  - Comparing electron microscopy and a competitive blocking ELISA in the detection
      of rotaviruses in porcine faeces.
AB  - Analysis of 476 faecal samples from diarrhoeic piglets was performed using
      electron microscopy (EM) and a competitive blocking (CB)-ELISA based on
      monoclonal antibodies to the VP6 protein of group A rotavirus. Rotavirus was
      detected by EM and/or CB-ELISA in 111 (23.3%) samples. Of these, all groups of
      rotavirus were identified in 83 (74.8%) samples by EM (EM+), while group A
      rotavirus was identified in 90 (81.1%) samples by CB-ELISA (ELISA+). However,
      only 62 (55.9%) of samples were positive using both detection methods. The
      finding of 28 (25.2%) EM-/CB-ELISA+ samples illustrated the high sensitivity of
      the CB-ELISA method. On PCR analysis, groups B and C rotavirus was found in 3 and
      16 of 19 EM+/CB-ELISA- samples, respectively. Although the study illustrates the
      high sensitivity of a CB-ELISA in rotavirus detection, the findings highlight the
      need to use a range of diagnostic methods in detecting these viruses in clinical
      samples.

PMID- 20036589
TI  - On the applications of micror=-1 metamaterial lenses for magnetic resonance
      imaging.
AB  - In this work some possible applications of negative permeability magnetic
      metamaterial lenses for magnetic resonance imaging (MRI) are analyzed. It is
      shown that using magnetic metamaterials lenses it is possible to manipulate the
      spatial distribution of the radio-frequency (RF) field used in MR systems and,
      under some circumstances, improve the sensitivity of surface coils. Furthermore a
      collimation of the RF field, phenomenon that may find application in parallel
      imaging, is presented. MR images of real tissues are shown in order to prove the
      suitability of the theoretical analysis for practical applications.

PMID- 20036590
TI  - Molecular simulations of ultra-low-energy nitrogen ion bombardment of A-DNA in
      vacuum.
AB  - For investigating mechanisms involved in low-energy ion beam induced mutation,
      besides experiments using low-energy and low-fluence ions to bombard naked DNA,
      molecular simulations were carried out as an effort towards the insight in
      molecular interactions between ions and DNA. In the current study, Monte Carlo
      (MC) and molecular dynamics (MD) simulations were applied. The results of MC
      simulations provide some clues about the interaction energies and sites of
      preference of N-ion bombardment on an A-DNA short duplex strand. MD simulations
      of a single N-ion moving towards the same DNA strand with different linear
      velocities corresponding to bombardment energies of 0.1, 1, 10 and 100 eV
      revealed information about changes in bond lengths and visibly distorted
      structures of bombarded nucleotides. The simulations demonstrated that ion
      bombardment-induced DNA change in structure was not a random but preferential
      effect.

PMID- 20036591
TI  - Structural comparison of mu-opioid receptor selective peptides confirmed four
      parameters of bioactivity.
AB  - Structural determinants of binding to the mu-opioid receptor, an important target
      in analgesia, attract great scientific attention. Many natural and synthetic
      peptides and peptidomimetics were shown previously to bind to this receptor
      selectively but there is no consensus about the structure responsible for
      biological activity. No high resolution structure of this receptor is available
      and the binding site of ligands is not exactly known. However, mu-opioid ligands
      with similar affinity and selectivity should possess at least one common
      structural feature. Comparative structural analysis of such ligands, considering
      adequate representation of binding conditions, may reveal key features of
      bioactivity. In this study ten mu-opioid receptor ligands, DAMGO, Tyr-W-MIF-1,
      morphiceptin, endomorphin-1 and 2 and their analogues, possessing different
      affinity and selectivity, were examined using molecular dynamics. Conformational
      preference of these molecules was determined in H(2)O and DMSO along with
      structural properties previously proposed to be important for binding. Four of
      such structural requirements were confirmed to be important, providing a possible
      structural model of receptor binding. Simultaneous fulfillment of these
      requirements results most likely in high affinity binding to the mu-opioid
      receptor.

PMID- 20036592
TI  - Human recombinant palmitoyl-protein thioesterase-1 (PPT1) for preclinical
      evaluation of enzyme replacement therapy for infantile neuronal ceroid
      lipofuscinosis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL, also known as Haltia-Santavuori
      disease) is a lysosomal storage disorder of infants and children characterized by
      blindness, seizures and a progressive neurodegenerative course. Recent clinical
      trials have involved neural stem cells and gene therapy directed to the central
      nervous system; however, enzyme replacement therapy has never been addressed. In
      the current paper, we describe the production of human recombinant PPT1 (the
      defective enzyme in INCL) by standard methods in Chinese Hamster Ovary (CHO)
      cells. The enzyme is largely mannose 6-phosphorylated as assessed by mannose 6
      phosphate receptor binding (80% bound) and taken up rapidly by immortalized
      patient lymphoblasts, where clearance of PPT substrates was demonstrated (EC(50)
      of 0.25 nM after overnight incubation). When injected intravenously into PPT1
      deficient mice, the clearance of recombinant human PPT1 from plasma was rapid,
      with a half-life of 10 min. Most of the injected dose was distributed to the
      kidney and liver and potentially corrective levels were also observed in heart,
      lung and spleen. Brain uptake was minimal, as expected based on experience with
      other intravenously administered lysosomal enzymes. The enzyme may be useful as
      an adjunct to central nervous system-directed therapies and could be used as a
      starting point for modifications designed to improve brain delivery.

PMID- 20036593
TI  - Lack of genotype-phenotype correlations and outcome in MCAD deficiency diagnosed
      by newborn screening in New York State.
AB  - INTRODUCTION: Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is one of the
      most common inborn errors of metabolism. Affected patients have impaired ability
      to break down medium chain fatty acids during fasting, and typically present in
      the early years of life with hypoketotic hypoglycemia, Reye syndrome-like
      symptoms, brain damage or death. The development of newborn screening (NBS) for
      MCAD deficiency has greatly improved outcome, but some patients still appear at
      risk for severe complications. We reviewed the outcome of patients identified
      with MCAD deficiency by the New York State NBS process to identify biochemical or
      genotypic markers which might predict outcome. METHOD: All eight NBS follow-up
      centers in New York State contributed the cases of MCAD deficiency diagnosed by
      newborn screen, who received diagnostic and follow-up care in their clinic. Data
      reviewed included gender, age, birthweight, initial NBS octanoylcarnitine level
      (C8) and C8/C2 ratio, follow-up C8 and hexanoylglycine, race/ethnicity, and
      presence of neonatal or later symptoms. RESULTS: We identified 53 cases of MCAD
      deficiency. More than one quarter of patients had a post-neonatal symptomatic
      admission (predominantly lethargy associated with an intercurrent illness). No
      genotype or C8 level was protective for neonatal or later symptoms. There was a
      relationship between initial C8 level or C8/C2 ratio and occurrence of later
      symptoms (7.3 micromol/L in the asymptomatic vs. 19.1 micromol/L in the
      symptomatic, p<0.0002 for C8, and 0.26 vs. 0.6, respectively, for C8/C2 ratio,
      p<0.012). Four infants had initial C8 level >30 micromol/L; these infants had a
      high rate of symptomatic or multiple symptomatic episodes or a history of sibling
      death from "SIDS", and typically had deletion, nonsense or splice sites
      mutations. Infants having a history of a symptomatic episode were more likely to
      have higher initial C8 on NBS and a genotype predicted to strongly affect protein
      function. In our ethnically diverse group of patients, the c.985A>G mutation was
      rarely found in non-Caucasians. DISCUSSION: No genotype or metabolite profile is
      protective from symptoms. The strong relationship between initial C8 level and
      outcome suggests that in at least some cases neonates having high initial C8
      levels may be demonstrating an increased susceptibility to catabolic stress, and
      may merit additional precautions. Our data also suggest that these infants are
      more likely to carry severe mutations including homozygosity for the common
      mutation, deletions, nonsense or splice site mutations. The reports of
      significant lethargy or hypoglycemia during intercurrent illness in over one
      quarter of cases even when early medical intervention is recommended (and even
      when initial C8 is not profoundly elevated) underscores the importance of
      continued vigilance to prevent stressful fasting in this disorder.

PMID- 20036594
TI  - Three Mendelian disorders (chronic granulomatous disease, retinitis pigmentosa,
      ornithine transcarbamylase deficiency) in a young woman with an X chromosome
      deletion, del(X)(p11.4p21.1).

PMID- 20036595
TI  - A detection method for streak artifacts and radiological noise in a non-uniform
      region in a CT image.
AB  - By using the CT images obtained by subtracting two CT images acquired under the
      same conditions and slice locations, we have devised a method for detecting
      streak artifacts in non-uniform regions and only radiological noise components in
      CT images. A chest phantom was scanned using 16- and 64-multidetector row helical
      CT scanners with various mAs values at 120kVp. The upper lung slice image was
      employed as a target image for evaluating the streak artifacts and radiological
      noise. One hundred parallel line segments with a length of 80 pixels were placed
      on the subtracted CT image, and the largest CT value in each CT value profile was
      employed as a feature variable of the streak artifacts; these feature variables
      were analyzed with the extreme value theory (Gumbel distribution). To detect only
      the radiological noise, all CT values contained in the 100 line profile were
      plotted on normal probability paper and the standard deviation was estimated from
      the inclination of its fitted line for the CT value plots. The two detection
      methods devised in this study were able to evaluate the streak artifacts and
      radiological noise in the CT images with high accuracy.

PMID- 20036596
TI  - DNA damage and plasma antioxidant indices in Bangladeshi type 2 diabetic
      patients.
AB  - BACKGROUND AND AIM: Diabetes mellitus is a complex metabolic disorder
      characterized by a disturbance in glucose metabolism. Recent evidence suggests
      that increased oxidative stress as well as alteration of antioxidant capacity may
      be related to the complications seen in patients with type 2 diabetes. The aim of
      this study was to measure serum antioxidant status in type 2 diabetic patients
      and to assess its relationship with oxidative DNA damage. METHODS: A total of 57
      subjects were included in this study. Of these, 32 were type 2 diabetic patients
      and 25 were non-diabetic subjects. Comet assay was used to quantify the level of
      DNA damage in lymphocytes. Spectrophotometric methods were used to assess serum
      levels of malondialdehyde (MDA) and protein carbonyl, and serum activity of
      superoxide dismutase (SOD) and the protein thiol (P-SH) group. RESULTS: A
      significant increase in mean comet tail DNA, indicating DNA damage, was observed
      in diabetic patients compared with controls. Diabetic patients had significantly
      higher levels of MDA and protein carbonyl in parallel with significant decreases
      in levels of SOD and the P-SH group compared with controls. Serum SOD was also
      inversely correlated with the increase in comet tail DNA. CONCLUSION: These
      results indicate the presence of significant lipid peroxidation, protein
      oxidation and oxidative DNA damage in patients with diabetes. Perturbation of
      glucose homoeostasis was associated with an increase in oxidants and a
      concomitant decrease of antioxidant enzymes in the type 2 diabetic patients'
      blood. The present study suggests that the status of oxidant-antioxidant
      imbalance may be one of the mechanisms leading to the DNA damage detected in the
      lymphocytes of type 2 diabetic patients.

PMID- 20036597
TI  - Sorption studies of nitrate ion by a modified beet residue in the presence and
      absence of ultrasound.
AB  - Kinetic and thermodynamic studies were carried out for the adsorption of nitrate
      ion from aqueous solutions onto modified beet residue and for desorption from the
      sorbent to the solution in batch experiments. The beet residue was modified by
      epichlorohydrin in the presence of pyridine. The experiments were conducted in
      the presence and absence of ultrasound. The removal of this ion was examined by
      varying experimental conditions such as the amount of sorbent, contact time,
      concentration, and temperature. It was found that more than 90% of nitrate ion
      was removed in less than 2 min from the solution. Results indicate that the
      adsorption of nitrate in the presence of ultrasound was higher at lower
      temperature (10 degrees C) and it was lower at higher temperatures with respect
      to the control method (without ultrasound). In the case of desorption study, the
      amount of desorption was higher in the presence of ultrasound than its absence at
      different applied temperatures. The Langmuir isotherm model fits adequately the
      experimental data for adsorption and desorption studies. In point of kinetics,
      the second-order kinetic model describes the sorption process for this ion. The
      thermodynamic parameters such as DeltaG degrees , DeltaH degrees , and DeltaS
      degrees were determined for the sorption of NO(3)(-) from the temperature
      dependence of the sorption process.

PMID- 20036598
TI  - Ultrasound and ionic-liquid-assisted synthesis and characterization of
      polyaniline/Y2O3 nanocomposite with controlled conductivity.
AB  - A sonochemical method has been employed to prepare polyaniline-Y(2)O(3)
      nanocomposite with controlled conductivity with the assistance of an ionic liquid
      (IL). Ultrasound energy and the IL replace conventional oxidants and metal
      complexes in promoting the polymerization of aniline monomer for the first time.
      Structural characterization has revealed that the resulting nanocomposite
      consists of microspheres of average diameter 3-5 microm. The products were found
      to consist of regular solid microspheres covered with some 40 nm nanoparticles.
      Under certain polymerization conditions, polyaniline nanofibers and nanosheet
      were obtained. The method may open a new pathway for the preparation of nanoscale
      conducting polymer nanocomposites with the aid of ILs. The conductivity of the
      product varies with the mass ratio of aniline monomer to Y(2)O(3) and IL. TG
      curves of the products suggest that the thermal degradation process of the
      PANI/Y(2)O(3) composites proceeds in two steps and that the composites are more
      thermally stable than pure PANI. The reaction conditions have been optimized by
      varying parameters such as the aniline/Y(2)O(3) ratio and the type and amount of
      IL used. The effect of the ultrasonic irritation time and frequency on the
      morphology, conductivity and yield were discussed.

PMID- 20036599
TI  - Biogenic volatile organic compounds and plant competition.
AB  - One of the most important factors to shape plant communities is competition
      between plants, which impacts on the availability of environmental factors such
      as light, nutrients and water. In response to these environmental parameters,
      plants adjust the emission of many different biogenic volatile organic compounds
      (BVOCs). BVOCs can also elicit responses in neighbouring plants, thus
      constituting a platform for plant-plant interactions. Here, we review the
      relationship between BVOC emissions and competition among neighbouring plants.
      Recent progress indicates that BVOCs can act both as allelochemicals and as
      neighbour detection signals. It is suggested that BVOCs provide information about
      neighbouring competitors, such as their identity or growth rate, that classic
      neighbour detection signals cannot provide.

PMID- 20036600
TI  - Marine bioinorganic materials: mussels pumping iron.
AB  - The oceans are filled with an amazing variety of biological materials including
      the glues and cements of mussels, barnacles, tube worms, algae, and starfish.
      Recent studies on mussel adhesive are providing increasing evidence for a unique
      mechanism of material generation involving iron-induced protein oxidation and
      cross-linking chemistry. Insights are also being gathered on many of the other
      marine creatures producing adhesives. Beyond understanding biology, this growing
      knowledge is inspiring application development. New classes of biomimetic
      polymers are poised to provide the next generation of surgical adhesives and
      orthopedic cements.

PMID- 20036601
TI  - Fluorescent imaging of transition metal homeostasis using genetically encoded
      sensors.
AB  - The ability to image the concentration of transition metals in living cells in
      real time is important for understanding transition metal (TM) homeostasis and
      its involvement in diseases. Genetically encoded fluorescent sensor proteins are
      attractive because they do not require cell-invasive procedures, can be targeted
      to different locations in the cell, and allow ratiometric detection. Important
      progress in the development of Zn(2+) sensors has allowed sensitive detection of
      the very low free concentrations of Zn(2+) in single cells, both in the cytosol
      and various organelles. Together with other recent advances in chemical biology,
      these tools seem particularly useful to interrogate the dynamics and
      compartmentation of TM homeostasis.

PMID- 20036602
TI  - TRAIL receptor targeting therapies for non-small cell lung cancer: current status
      and perspectives.
AB  - Non-small cell lung cancer (NSCLC) is a common and often fatal malignancy,
      diagnosed at an advanced stage in more than half of the cases. Chemo-resistance
      remains a major problem in the treatment of NSCLC patients with conventional
      chemotherapeutic agents. Therefore main research efforts are focused on the
      development of novel targeted agents. In this review we provide an overview on
      the use of TNF-related apoptosis-inducing ligand (TRAIL) receptor targeting
      agents in NSCLC models and in early clinical studies. Different TRAIL receptor
      targeting agents are available which have been tested in NSCLC models and some
      were tested in the clinic. The efficacy of these drugs as single agents in NSCLC
      models is discussed as well as different mechanisms of resistance that are found
      in NSCLC cell lines. In order to maximize sensitivity to TRAIL receptor targeting
      drugs, combined use with other drugs is of interest. The current status of tested
      combinations of TRAIL receptor targeting agents with other therapeutics, such as
      classical cytotoxics, Bcl-2 family targeting agents, proteasome inhibitors, EGFR
      inhibitors, histone deacetylase inhibitors and COX-2 inhibitors as well as their
      mechanisms in preclinical studies are discussed. Clinical studies on TRAIL
      targeted therapies in which NSCLC patients were included are discussed and future
      perspectives are considered.

PMID- 20036603
TI  - Evaluation of cornulin, keratin 4, keratin 13 expression and grade of dysplasia
      for predicting malignant progression of oral leukoplakia.
AB  - Oral leukoplakia is defined as a white patch in the oral cavity that cannot be
      diagnosed as any other known disorder. These lesions carry an increased risk of
      malignant progression, and approximately 2-3% per year do progress to cancer. At
      present biopsies are histopathologically graded for dysplasia to assess the risk
      of progression, but this grading is somewhat subjective and of limited use for
      the individual patient. In a previous study we discovered by a comprehensive
      proteomics approach that compared to normal mucosa, protein expression of
      cornulin, keratin 4 and keratin 13 is decreased in tumors and severe dysplasia,
      preneoplastic tissue with a high risk of malignant progression. Here, we studied
      whether loss of expression of these proteins can predict malignant transformation
      of oral leukoplakia. Biopsies of 12 progressing and 36 non-progressing
      leukoplakia lesions were analyzed for cornulin, keratin 4 and keratin 13
      expression by immunohistochemistry, and graded for dysplasia. Kaplan-Meier
      analysis showed that loss of expression of neither cornulin (p=0.075), keratin 4
      (p=0.789) nor keratin 13 (p=0.732) was significantly associated with malignant
      transformation of leukoplakia lesions. However, decreased expression of these
      proteins was significantly associated with the presence of hyperkeratosis. Only
      dysplasia grading correlated significantly with malignant progression of
      leukoplakia (p=0.024). Despite the promising outlook that decreased cornulin,
      keratin 4 and keratin 13 expression in the oral mucosa is associated with a
      premalignant state, these markers do not predict malignant transformation of
      leukoplakia lesions. The most likely explanation is that the aberrant
      differentiation state of hyperkeratotic leukoplakia lesions already causes a
      decreased expression, obscuring the putative association with malignant
      transformation. Our results support the significance of dysplasia grading for the
      prediction of malignant transformation.

PMID- 20036604
TI  - Anti-invasion and anti-tumor growth effect of doxycycline treatment for human
      oral squamous-cell carcinoma--in vitro and in vivo studies.
AB  - Regional lymph node and distant organ metastasis of oral squamous-cell carcinoma
      (OSCC) has been associated with increased production of matrix metalloproteases
      (MMPs), and scientific data showed that doxycycline (Dox) could down-regulate the
      expression of MMPs. The objective of this study was to evaluate the effect of Dox
      on the expression of MMPs in vitro using the SCC-15 cell line and in vivo SCC-15
      xenografted nude mice. SCC-15 cells maintained under distinct culture conditions
      expressed high levels of pro-MMP-2 and pro-MMP-9; however, as determined by
      zymography and Western blot analysis, Dox significantly reduced the production of
      pro-MMP-2 and pro-MMP-9 after 24h of treatment in a dose-dependent manner (2.5-40
      microg/ml). Dox (10 microg/ml) decreased the expression of MMP-9 mRNA but did not
      alter the level of MMP-2 mRNA after 24h of treatment. In addition, this drug
      significantly inhibited the invasive and migration activities of SCC-15 cells in
      vitro (>75% inhibition at 10 microg/ml). On the other hand, daily administration
      of Dox (3mg/mice) restrained tumor growth in SCC-15 xenografted nude mice, with
      an inhibition rate of 85.6%. Compared with the control group (treated with normal
      saline), MMP-9 mRNA levels in the fresh tumor tissue decreased upon Dox treatment
      (P<0.01) while MMP-2 mRNA levels were unchanged. In conclusion, reduced
      expression of MMP-9 at the transcriptional level and MMP-2 at the post
      transcriptional level caused by Dox was found to be associated with decreased
      invasion of oral SCC in vitro. Moreover, Dox exerted a significant suppressive
      effect on tumor growth in an in vivo nude mice model. Taken together, these
      results, to our knowledge, may first imply that Doxycycline has an adjuvant
      therapeutic effect on OSCC that is associated with inhibition of MMPs expression.

PMID- 20036605
TI  - Mate drinking and oral and oro-pharyngeal cancer: a systematic review and meta
      analysis.
AB  - In Latin America, mate is consumed as a beverage regularly. Among the cancers
      that are associated with mate drinking is oral and oro-pharyngeal cancer,
      incidence of which is high in the region. In order to further understand this
      association between mate drinking and the risk of oral and oro-pharyngeal cancer,
      we performed a systematic review and meta-analysis of related studies. All
      relevant studies published in English as original articles up to June 2009 were
      identified through a literature search using PubMed and Medline and by reviewing
      the references from the retrieved articles. Four case-control studies done in
      Latin America were identified. There were 879 mate users and 1128 non- or low
      mate users in those studies with a total of 566 oral and oro-pharyngeal cancers.
      The adjusted association between mate drinking and oral and oro-pharyngeal cancer
      was significant within 3 of those studies. Meta-analysis yielded a significant
      summary odds ratio (OR) of 2.11 (95% confidence interval=1.39-3.19). Population
      Attributable Risk for mate drinking was 16%. While the epidemiological data
      indicate that mate users have an increased risk of oral and oro-pharyngeal
      cancer, little is known about whether this increased risk is due to the high
      temperature of the beverage when it is consumed or due to certain carcinogenic
      constituents that are present in mate. More human and animal studies are needed
      before a conclusion can be made on the oral and oro-pharyngeal carcinogenic risk
      of mate to humans.

PMID- 20036606
TI  - Effect of local hyperthermia on lymphangiogenic factors VEGF-C and -D in a nude
      mouse xenograft model of tongue squamous cell carcinoma.
AB  - It is widely accepted that tumor-induced lymphangiogenesis driven by vascular
      endothelial growth factor (VEGF)-C- and/or VEGF-D-induced activation of VEGF
      receptor (VEGFR)-3 could promote lymphatic metastasis. In this study, tumor
      growth and intratumoral expression level of VEGF-C and -D following
      administration of local hyperthermia was evaluated in nude mice model of tongue
      squamous cell carcinoma (SCC). The data demonstrated that the size of tumor in
      local hyperthermia was 26.5% of control group, and that local hyperthermia
      markedly suppressed the mRNA and protein expression of VEGF-C and -D as
      determined by quantitative real-time RT-PCR, Western blot and
      immunohistochemistry (P<0.05). These results suggest that, accompanying with
      tumor growth inhibition, local hyperthermia may act as an anti-lymphangiogenic
      role by suppressing the expression of tumor VEGF-C and -D, and thereby inhibiting
      cancer cell lymphatic metastasis in tongue SCC.

PMID- 20036607
TI  - A basal-cell-like compartment in head and neck squamous cell carcinomas
      represents the invasive front of the tumor and is expressing MMP-9.
AB  - Head and neck squamous cell carcinomas (HNSCCs) are the most frequent
      malignancies of the upper aerodigestive tract. The cancer stem cell (CSC)
      hypothesis concludes that CSCs constitute the dangerous tumor cell population due
      to their ability of self-renewal and being associated with relapse of tumor
      disease, invasiveness and resistance to chemo(radio)therapy. The aim of this
      study was to look for CSC candidates and expression of MMP-9 that previously was
      implicated in HNSCC invasiveness. Immunohistochemical, immunofluorescence and
      Western blot analysis were performed on HNSCC tumor specimens using antibodies
      specific for MMP-9, CD44, ALDH1 and CK14. Gelatinolytic activity was assessed by
      zymography. Pearson correlation analysis was used for statistical comparison.
      Immunohistochemical analysis found CD44 and MMP-9 to co-localize in tumor cells
      at the invasive front. Western blot analysis demonstrated a significant
      correlation (p=0.0047) between CD44 and MMP-9 in the tested tissues. In addition
      gelatinolytic activity of HNSCC tissues was found to significantly correlate
      (p=0.0010) with MMP-9 expression. The CD44(+) invasive front of the tumor was
      also positive for ALDH1 and CK14, all of them being typically expressed by cells
      in the basal cell layer of normal stratified squamous epithelia that also harbors
      the epithelial stem cells. The observations point to a role of a MMP-9 positive
      basal-cell-like cell layer in the process of HNSCC invasiveness. This compartment
      likely contains CSCs since it is expressing the putative CSC markers CD44, ALDH1
      and CK14. This cell layer therefore should be considered a major therapeutic
      target in the treatment of head and neck cancer.

PMID- 20036608
TI  - Inhibition of tumorigenicity and enhancement of radiochemosensitivity in head and
      neck squamous cell cancer-derived ALDH1-positive cells by knockdown of Bmi-1.
AB  - Bmi-1, a member of the Polycomb family of transcriptional repressors, is
      essential for maintaining the self-renewal abilities of adult stem cells. Bmi-1
      has been demonstrated to play a role in tumorigenesis in head and neck squamous
      cell carcinomas (HNSCCs). A recent study has further suggested that ALDH1 may be
      considered to be a putative marker for HNSCC-derived cancer stem cells. However,
      the role that Bmi-1 plays in HNSCC-derived ALDH1-positive cells (HNSCC-ALDH1(+))
      has yet to be determined. In this study, we demonstrated that HNSCC-ALDH1(+)
      cells possess tumor initiating properties, are capable of self-renewal, and
      express higher levels of Bmi-1 as compared to HNSCC-ALDH1(-) cells. To further
      explore the functional role of Bmi-1 in HNSCC-ALDH1(+) cells, we used a
      lentiviral vector expressing shRNA to knock down Bmi-1 expression (sh-Bmi-1) in
      HNSCC-ALDH1(+) cells. Silencing of Bmi-1 significantly enhanced the sensitivity
      of HNSCC-ALDH1(+) cells to chemoradiation and increased the degree of
      chemoradiation-mediated apoptosis that occurred. Importantly, knockdown of Bmi-1
      increased the effectiveness of radiotherapy and led to the inhibition of tumor
      growth in nude mice transplanted with HNSCC-ALDH1(+) cells. Kaplan-Meier survival
      analysis indicated that the mean survival rate of HNSCC-ALDH1(+) tumor-bearing
      immunocompromised mice treated with radiotherapy was significantly improved by
      treatment with sh-Bmi-1 as well. In summary, these results suggest that Bmi-1 is
      a potential target for increasing the sensitivity of HNSCC cancer stem cells to
      chemoradiotherapy.

PMID- 20036609
TI  - Head and neck cancer surgery in the elderly--does age influence the postoperative
      course?
AB  - There are few data focusing on postoperative course after major head and neck
      cancer surgery in the elderly compared with the younger population. The aim of
      this study was to assess the impact of age on postoperative outcomes. At hospital
      admission, we prospectively collected data from 261 patients separated into two
      groups with regard to their age (those >or= 70 years and those < 70 years).
      Twenty-nine of them were over 70 years old. Median length of stay was similar in
      both populations (22 vs. 21 days, p=0.66). Incidence of severe postoperative
      complications was similar: surgical site infection (6/29 vs. 89/232, p=0.77),
      pneumonia (4/29 vs. 29/232, p=0.13) and infection caused by multi-resistant
      pathogens (1/29 vs. 14/232, p=0.08). There was no significant increase in
      postoperative deaths (4/29 vs. 6/232, p=0.12). The impact of age on postoperative
      deaths was assessed after adjustment for potential risk factors. In a logistic
      regression model, postoperative death risk remained insignificantly increased in
      the elderly (adjusted Odds Ratio=3.3 [0.7-14.9], p=0.22). In our experience, the
      postoperative course in elderly patients is not significantly different from that
      than in younger patients.

PMID- 20036610
TI  - Moderate predictive value of demographic and behavioral characteristics for a
      diagnosis of HPV16-positive and HPV16-negative head and neck cancer.
AB  - Patients with HPV-positive and HPV-negative head and neck squamous cell carcinoma
      (HNSCC) are significantly different with regard to sociodemographic and
      behavioral characteristics that clinicians may use to assume tumor HPV status.
      Machine learning methods were used to evaluate the predictive value of patient
      characteristics and laboratory biomarkers of HPV exposure for a diagnosis of
      HPV16-positive HNSCC compared to in situ hybridization, the current gold
      standard. Models that used a combination of demographic characteristics such as
      age, tobacco use, gender, and race had only moderate predictive value for tumor
      HPV status among all patients with HNSCC (positive predictive value [PPV]=75%,
      negative predictive value [NPV]=68%) or when limited to oropharynx cancer
      patients (PPV=55%, NPV=65%) and thus included a sizeable number of false positive
      and false negative predictions. Prediction was not improved by the addition of
      other demographic or behavioral factors (sexual behavior, income, education) or
      biomarkers of HPV16 exposure (L1, E6/7 antibodies or DNA in oral exfoliated
      cells). Patient demographic and behavioral characteristics as well as HPV
      biomarkers are not an accurate substitute for clinical testing of tumor HPV
      status.

PMID- 20036611
TI  - Contemporary reconstruction of the mandible.
AB  - Reconstruction of the mandible has evolved significantly over the last 40years.
      Early attempts were often disfiguring and wrought with complications but with the
      introduction of free tissue transfer of well vascularized bone in the 1970's
      there was a significant improvement in outcomes. In recent years the harvest,
      inset, and microvascular anatomosis have been refined to the point that success
      rates are reported as high as 99% throughout the literature. Focus has now
      shifted to optimizing functional and aesthetic outcomes after mandible
      reconstruction. This paper will be a review defect classification, goals of
      reconstruction, the various donor sites, dental rehabilitation, new advances, and
      persistent problems. Reconstruction of segmental mandibular defects after
      ablative surgery is best accomplished using free tissue transfer to restore
      mandibular continuity and function. Reestablishing occlusion and optimizing
      tongue mobility are important to post-operative oral function. Persistent
      problems in oro-mandibular reconstruction relate to the effects of radiation
      treatment on the native tissue and include xerostomia, dysgeusia,
      osteoradionecrosis and trismus. These problems continue to plague the oral cancer
      patient despite the significant advances that allow a far more complete
      functional restoration than could be accomplished a mere two decades ago.

PMID- 20036614
TI  - Star-shaped azomethines based on tris(2-aminoethyl)amine. Characterization,
      thermal and optical study.
AB  - The synthesis and detailed (physico)-chemical ((1)H/(13)C NMR, FTIR, UV-vis and
      elemental analysis) characterizations of new star-shaped compounds based on
      tris(2-aminoethyl)amine, including in their structure an azomethine function (HCN
      ) and alkoxysemiperfluorinated (-O-(CH(2))(3)-(CF(2))(7)-CF(3)), octadecyloxy
      aliphatic (-O-(CH(2))(17)-CH(3)) chain or two phenyl rings (-Ph-Ph-) as a
      terminal group, were reported. The mesomorphic behavior was investigated by means
      of differential scanning calorimetry (DSC), polarized optical microscopy (POM)
      and additionally by FTIR(T) and UV-vis(T) spectroscopy. Wide-angle X-ray
      diffraction (WAXD) technique was used to probe the structural properties of the
      azomethines. Moreover, the azomethine A1 was electro-spun to prepare fibers with
      poly(methyl methacrylate) (PMMA) and investigated by DSC and POM. Additionally, a
      film of the A1 with PMMA was cast from chloroform and the thermal properties of
      the film were compared with the thermal properties of the fiber and powder. It
      was showed that terminal groups dramatically influence the thermal and optical
      properties of the star-shaped azomethines.

PMID- 20036612
TI  - Omics meet networks - using systems approaches to infer regulatory networks in
      plants.
AB  - Many genomic-scale datasets in plants have been generated over the last few
      years. This substantial achievement has led to impressive progress, including
      some of the most detailed molecular maps in any multicellular organism. Networks
      and pathways have been reconstructed using transcriptome, genome-wide
      transcription factor binding, proteome and metabolome data, and subsequently used
      to infer functional interactions among genes, proteins, and metabolites. However,
      more sophisticated systems biology approaches are needed to integrate different
      omics datasets. Ultimately, the integration of diverse and massive datasets into
      coherent models will improve our understanding of the molecular networks that
      underlie biological processes.

PMID- 20036613
TI  - Hijacking the host ubiquitin pathway: structural strategies of bacterial E3
      ubiquitin ligases.
AB  - Ubiquitinylation of proteins is a critical mechanism in regulating numerous
      eukaryotic cellular processes including cell cycle progression, inflammatory
      response, and vesicular trafficking. Given the importance of ubiquitinylation, it
      is not surprising that several pathogenic bacteria have developed strategies to
      exploit various stages of the ubiquitin pathway for their own benefit. One such
      strategy is the delivery of bacterial 'effector' proteins into the host cell
      cytosol, which mimic the activities of components of the host ubiquitin pathway.
      Recent studies have highlighted a number of bacterial effectors that functionally
      mimic the activity of eukaryotic E3 ubiquitin ligases, including a novel
      structural class of bacterial E3 ligases that provides a striking example of
      convergent evolution.

PMID- 20036615
TI  - Cu(II), Co(II), Ni(II), Mn(II), and Fe(II) metal complexes containing N,N'-(3,4
      diaminobenzophenon)-3,5-Bu(t)(2)-salicylaldimine ligand: Synthesis, structural
      characterization, thermal properties, electrochemistry, and
      spectroelectrochemistry.
AB  - The synthesis, structure, spectroscopic and electro-spectrochemical properties of
      steric hindered Schiff-base ligand [N,N'-(3,4-benzophenon)-3,5-Bu(t)(2)
      salicylaldimine (LH(2))] and its mononuclear Cu(II), Co(II), Ni(II), Mn(II) and
      Fe(II) complexes are described in this work. The new dissymmetric steric hindered
      Schiff-base ligand containing a donor set of NONO was prepared through reaction
      of 3,4-diaminobenzophenon with 3,5-Bu(t)(2)-salicylaldehyde. Certain metal
      complexes of this ligand were synthesized by treating an ethanolic solution of
      the ligand with an equimolar amount of metal salts. The ligand and its complexes
      were characterized by FT-IR, UV-vis, (1)H NMR, elemental analysis, molar
      conductivity and thermal analysis methods in addition to magnetic susceptibility,
      electrochemistry and spectroelectrochemistry techniques. The tetradentate and
      mononuclear metal complexes were obtained by reacting N,N'-(3,4-benzophenon)-3,5
      Bu(t)(2)-salicylaldimine (LH(2)) with some metal acetate in a 1:1 mole ratio. The
      molar conductance data suggest metal complexes to be non-electrolytes.

PMID- 20036616
TI  - In situ investigations of vault paintings in the Antwerp cathedral.
AB  - X-ray fluorescence spectroscopy (XRF) and Raman spectroscopy have been used to
      examine 15th century mediaeval and 16th century renaissance vault paintings in
      the Our Lady's Cathedral (Antwerp, Belgium) in view of their restoration. The use
      of mobile instruments made it possible to work totally non-destructively. This
      complementary approach yields information on the elemental (XRF) and on the
      molecular composition (Raman) of the pigments. For the 15th century vault
      painting the pigments lead-tin yellow (Pb(2)SnO(4)), lead white
      (2PbCO(3)xPb(OH)(2)), vermilion (HgS), massicot (PbO) and azurite
      (2CuCO(3).Cu(OH)(2)) could be identified. The pigments used for the 16th century
      vault painting could be identified as red lead (Pb(3)O(4)), hematite (Fe(2)O(3)),
      lead white (2PbCO(3)xPb(OH)(2)) and azurite (2CuCO(3)xCu(OH)(2)). For both
      paintings the presence of the strong Raman scatterer calcite (CaCO(3)) resulted
      in a difficult identification of the pigments by Raman spectroscopy. The presence
      of gypsum (CaSO(4)x2H(2)O) on the mediaeval vault painting probably indicates
      that degradation took place.

PMID- 20036617
TI  - Newly recognized bocaviruses (HBoV, HBoV2) in children and adults with
      gastrointestinal illness in the United States.
AB  - BACKGROUND: The human bocavirus (HBoV) is a newly recognized parvovirus
      associated with respiratory and gastrointestinal disease. Recently, two new
      members of the parvovirus family have been recognized, HBoV2 and HBoV3.
      OBJECTIVES: Here we investigate stool and respiratory samples for the presence of
      HBoV, HBoV2 and HBoV3. STUDY DESIGN: Stool samples collected from 12/1/2007 to
      3/31/2008 were screened by PCR for the presence of HBoV, HBoV2, and HBoV3.
      Extracted DNA from respiratory specimens archived between 10/17/2005 and
      3/29/2006 were screened by PCR for HBoV2 and HBoV3. Medical records for all
      bocavirus positive patients were reviewed. RESULTS: Of 479 stool samples
      screened, 328 (68.5%) were from adults, and 151 (31.5%) were from children.
      Sixteen (3.4%) patients were positive for the presence of a bocavirus, including
      10 (2.1%) HBoV and 6 (1.3%) HBoV2. No HBoV3 was detected in stool samples.
      Frequency of HBoV and HBoV2 in stool samples from children was 3.3% and 0.7%, and
      from adults was 1.5% and 1.5% respectively. Clinical findings in patients with
      HBoV and HBoV2 in stool include diarrhea (50% and 83.3%), abdominal pain (40%,
      33.3%), and cough (10%, 50%). Of 868 respiratory samples screened, none were
      positive for either HBoV2 or HBoV3. CONCLUSIONS: The newly recognized parvovirus
      HBoV2 circulates in the United States. Patients with bocaviruses in stool have
      evidence of gastrointestinal illness. HBoV2 was not detected in respiratory
      samples. HBoV3 was not detected in either stool or respiratory samples.

PMID- 20036618
TI  - Increased motor cortical excitability after whole-hand electrical stimulation: a
      TMS study.
AB  - OBJECTIVE: To examine the neuromodulatory effect of whole-hand mesh-glove (MG)
      stimulation on motor cortical pathways, we explored motor cortical excitability
      before and after suprathreshold whole-hand MG stimulation using transcranial
      magnetic stimulation (TMS). METHODS: Twenty-eight healthy volunteers (14
      controls) were studied at baseline, immediately post and 1h post-MG stimulation
      for 30 min. Motor thresholds (MTs), motor evoked potentials (MEPs) recruitment
      curve, short intracortical inhibition (SICI) and intracortical facilitation (ICF)
      after paired magnetic stimuli were evaluated. RESULTS: After MG stimulation the
      MTs were significantly reduced and slope of MEP recruitment curve significantly
      increased; furthermore, the stimulation led to a sustained decrease of SICI and
      increase of ICF in the contralateral motor cortex. These effects lasted for at
      least 60 min and were stronger 1h post-stimulation compared with testing
      immediately after stimulation. A sham group did not show any differences before
      and after MG stimulation. CONCLUSIONS: We provide a first demonstration that MG
      whole-hand stimulation induces increases in motor cortical excitability lasting
      at least 1h. Both the strength of the corticospinal projections and the
      inhibitory and facilitatory intracortical mechanisms are involved. Synaptic
      modifications such as long-term potentiation mechanisms may underlie this
      stimulation-induced cortical plasticity changes. SIGNIFICANCE: Present results
      prove the MG stimulation to be a promising tool in neurorehabilitation.

PMID- 20036619
TI  - Acupuncture needles over the myocardium.

PMID- 20036620
TI  - GSTT1 and GSTM1 null mutations and adverse reactions induced by antituberculosis
      drugs in Koreans.
AB  - Adverse reactions induced by antituberculosis drugs (ATD) often result in serious
      morbidities, impeding scheduled treatment and cure. In the development of ATD
      induced adverse reactions, glutathione S-transferase has been suggested to play a
      protective role as an intracellular scavenger by conjugating toxic reactive
      metabolites of ATD. This study examined the association of null mutations in GST
      enzyme genes (GSTT1 and GSTM1) with the development of ATD-induced hepatitis and
      cutaneous reactions. We compared the frequencies of GSTT1 and GSTM1 null
      mutations in 57 patients with hepatitis, 94 patients with cutaneous adverse
      reactions, and 190 ATD-tolerant controls. The frequency of null mutations in
      GSTT1 and GSTM1 in patients with ATD-induced hepatitis was not significantly
      different from that of controls (59.6% vs. 54.2% and 45.6% vs. 54.7%,
      respectively). Additionally, no significant difference was observed in the
      frequency of either null mutation in patients with ATD-induced cutaneous
      reactions, including maculopapular eruption, compared with controls (58.5% vs.
      54.1% for GSTT1 and 59.6% vs. 54.6% for GSTM1). These findings indicate that
      GSTT1 and GSTM1 null mutations are not associated with the development of ATD
      induced hepatitis or cutaneous reactions in this Korean population, and suggest
      that glutathione S-transferase enzymes do not play important roles in the
      pathogenesis of these conditions.

PMID- 20036621
TI  - An unusual occurrence of chondromyxoid fibroma with secondary aneurysmal bone
      cyst in the cervical spine.
AB  - BACKGROUND CONTEXT: Chondromyxoid fibroma (CMF) and aneurysmal bone cysts (ABCs)
      are rare bone tumors and even rarer in the spine. To date, no report has been
      made of CMF with secondary ABC in the cervical spine. PURPOSE: The purpose of
      this study was to describe the diagnosis and surgical treatment of a case of CMF
      with secondary ABC of C6, a rare occurrence in an uncommon location. STUDY
      DESIGN: The study design is a case report. METHODS: A 27-year-old woman presented
      with numbness with paresthesias of the right upper extremity. Diagnostic imaging
      revealed diffuse enlargement of the right C6 lamina extending into the pedicle
      and medial facet joint. Surgical treatment consisted of complete C6 laminectomy,
      total resection of the extradural cervical mass, posterior lateral fusion at C5
      C7, and posterior segmental instrumentation from C5 to C7. Histopathology was
      consistent with CMF with secondary ABC. RESULTS: Laminectomy and instrumented
      segmental fusion provided an excellent clinical outcome. The instrumented fusion
      maintained the sagittal balance of the spine and stabilized across a complete
      facetectomy. The excision will likely avoid recurrence of the lesion.
      CONCLUSIONS: Treatment of CMF and ABC is challenging in the spine because of the
      proximity to neural structures. Aggressive surgical treatment makes recurrence
      less likely but creates the risk of spinal instability. Adequate surgical
      treatment needs to provide spinal stability.

PMID- 20036622
TI  - Pediatric transverse sacral fracture with cauda equina syndrome.
AB  - BACKGROUND CONTEXT: Transverse sacral fracture in pediatric patients is extremely
      uncommon with only nine cases reported in literature so far. PURPOSE: The purpose
      of this study was to heighten awareness and treatment options of a rare injury of
      traumatic pediatric transverse sacral fracture with cauda equina syndrome. STUDY
      DESIGN: This is a clinical case report and literature review. METHODS: We report
      a case of a 13-year-old girl with a Type III Roy-Camille, Zone III Denis sacral
      fracture whose only neurological deficit was a cauda equina syndrome with bowel
      and bladder involvement. She underwent emergent sacral laminectomy and surgical
      stabilization to decompress the cauda equina. RESULTS: The patient regained bowel
      and bladder function at 6-month follow-up. CONCLUSIONS: This case is presented to
      highlight the rarity of a pediatric transverse sacral fracture, which requires a
      high index of suspicion as early decompression helps in reversing the
      neurological deficit.

PMID- 20036623
TI  - Using short columns to speed up LC-MS quantification in MS binding assays.
AB  - The present study describes the use of short columns to speed up LC-MS
      quantification in MS binding assays. The concept of MS binding assays follows
      closely the principle of traditional radioligand binding but uses MS for the
      quantification of bound marker thus eliminating the need for a radiolabelled
      ligand. The general strategy of increasing the throughput of this type of binding
      assay by the use of short columns is exemplified for NO 711 binding addressing
      GAT1, the most prevalent GABA transporter in the CNS. Employing short RP-18
      columns with the dimension of 20 mm x 2 mm and 10 mm x 2 mm at flow rates up to
      1000 microL/min in an isocratic mode retention times of 8-9s and chromatographic
      cycle times of 18s could be achieved. Based on the internal standard [(2)H(10)]NO
      711 fast chromatography methods were developed for four different columns that
      enabled quantification of NO 711 in a range from 50 pM up to 5 nM directly out of
      reconstituted matrix samples without further sample preparation. A validation of
      the established methods with respect to linearity, intra- and inter-batch
      accuracy and precision showed that the requirements according to the FDA
      guideline for bioanalytical methods are met. Furthermore the established short
      column methods were applied to the quantification of NO 711 in saturation
      experiments. The results obtained (i.e., K(d)- and B(max)-values) were almost
      identical as compared to those determined employing standard column dimension (55
      mm x 2 mm).

PMID- 20036624
TI  - Separation of 2-aminobenzamide labeled glycans using hydrophilic interaction
      chromatography columns packed with 1.7 microm sorbent.
AB  - Separation by hydrophilic interaction chromatography (HILIC) with fluorescence
      detection utilizing a sub-2 microm glycan column for the separation of 2
      aminobenzamide (2-AB) labeled N-linked glycans is described. The HILIC column
      packed with a 1.7 microm amide sorbent improves the peak capacity compared to a
      3.0 microm HILIC column by a similar degree as observed in reversed-phase ultra
      performance liquid chromatography (RP-UPLC). The results indicated that the
      optimal peak capacity was achieved at flow rate 0.2-0.5 mL/min. HILIC method
      transfer guidelines were shown to further enhance the resolution of glycans by
      changing initial gradient conditions, flow rate, column temperature, and
      different column lengths. Additionally, excellent resolution can be achieved in
      the separation of 2-AB labeled glycans released from fetuin, RNase B, and human
      IgG with a rapid analysis time.

PMID- 20036625
TI  - Emerging issues in the use of transjugular intrahepatic portosystemic shunt
      (TIPS) for management of portal hypertension: time to update the guidelines?
AB  - Since its first introduction in the 1980s, transjugular intrahepatic
      portosystemic shunt has played an increasingly important role in the management
      and treatment of the complications of portal hypertension. In 2005, the American
      Association for the Study of Liver Diseases published the Practice Guidelines for
      the use of transjugular intrahepatic portosystemic shunt in the management of
      portal hypertension. Since then, technical advances and new interesting data on
      transjugular intrahepatic portosystemic shunt have been presented in the
      literature. The present review focus on the applications of transjugular
      intrahepatic portosystemic shunt and examines more recent studies on this topic;
      the current guidelines on the use of transjugular intrahepatic portosystemic
      shunt are also discussed. From the data presented in the most recent
      publications, it has become increasingly clear that the recommendations stemming
      from the current guidelines need to be reviewed and updated in several points.
      Changes in the American Association for the Study of Liver Diseases Practice
      Guidelines are needed for both common indications (variceal bleeding and
      refractory ascites) as well as uncommon ones (i.e., Budd-Chiari syndrome and
      portal cavernoma). In addition, a relevant technical advance has been the
      introduction of the polytetrafluoroethylene-covered stents, which greatly
      improved the patency and clinical efficacy of transjugular intrahepatic
      portosystemic shunt. Consequently, new studies are required to re-assess the role
      of transjugular intrahepatic portosystemic shunt performed with new covered
      stents as compared with other strategies in the management of portal
      hypertension.

PMID- 20036626
TI  - [Importance of clinical pharmacology in pediatrics].

PMID- 20036627
TI  - Foster replantation of fingertip using neighbouring digital artery in a young
      child.
AB  - Reconstruction of an amputated fingertip in a young child demands special
      techniques for success. We report a 2.5-year-old female patient with an amputated
      left index fingertip with the vascular defect being too severe to perform the
      usual replantation. Comparing several methods, we used the neighbouring digital
      artery as the feeding artery to perform foster replantation. Finally, the patient
      was satisfied with the appearance and function of her fingers. The clinical case,
      techniques, results are described and discussed. We consider it a useful
      technique, especially for those with a rather severe vascular defect. PATIENT: A
      2.5-year-old girl suffered a crush amputation of the left index fingertip. Only
      the flexor tendon of the amputated fingertip was connected to the proximal finger
      tissue and the blood supply was completely lost (Figure 1). METHODS: The distal
      amputated fingertip was fixed using Kirschner wire under general anaesthesia.
      Then, microsurgery operation was carried out immediately to replant this
      amputated fingertip. Both ulnar and radial digital arteries were avulsed, while
      the dorsal vein was intact and the digital nerve was also surviving. The
      integrity of blood vessels was too traumatised to connect to the proximal part.
      In the case of the distal part of the ulnar artery of the injured index finger,
      the blood supply was established by anastomosing the distal end of the amputated
      tip and the radial artery of the middle finger, which was the feeding artery
      (Figure 2). A 11/0 nylon suture was used. The dorsal vein and digital nerve were
      repaired by means of microsurgical anastomosis. The wound was covered with the
      dorsal skin of the middle finger and the palmar skin of the index finger to form
      a skin pedicle, and then, immobility of the two fingers was maintained to prevent
      avulsion. RESULT: The index tip obtained good blood supply and survived
      completely (Figure 3). Detachment of the index and middle finger was performed
      after 3 weeks, and both of the fingers showed good blood supply (Figure 4). The
      appearance and function of the index and middle fingers were satisfactory 3
      months postoperatively.

PMID- 20036628
TI  - Combined early cleft lip and palate repair in children under 10 months--a series
      of 106 patients.
AB  - This article reviews a series of 106 patients presenting with cleft lip and
      palate who underwent a simultaneous combined cleft lip and palate repair under
      the age of 10 months. The technique is described together with the early
      postoperative results. A single surgeon (the author) operated on the 106
      patients. The youngest patient was 6 weeks old, and the smallest weighed 2.3 kg.
      All patients underwent palate repair, followed by lip repair, at a single
      sitting. The palate repair used the Sommerlad technique with radical muscle
      repositioning and bilateral lateral Langenbeck-type releasing incisions when
      indicated. Of the total, 71 patients (67%) had a unilateral lip and palate cleft
      and underwent a modified Millard repair; 34 (32%) had a bilateral lip defect and
      underwent a modified Mulliken repair; and one (1%) had a midline cleft lip. Ten
      patients were excluded from the study, as their palate was deemed too wide to
      close. Instead, they underwent cleft lip repair and vomer flap to the anterior
      palate alone. The mean duration of the procedure was 97 min. There was neither
      mortality, nor significant anaesthetic complications. Two patients who had low
      oxygen saturation postoperatively were taken back to the theatre. In both cases,
      the soft palate sutures were removed and the airway improved to a safe degree,
      permitting return to the ward for subsequent final repair. All patients were
      discharged home without any ongoing problems. One patient subsequently developed
      a unilateral dehiscence of a bilateral lip, and seven patients underwent a second
      procedure to close a palatal fistula. Early follow-up results are encouraging,
      with only 8% of patients to date requiring a second procedure. CONCLUSION:
      Although technically challenging, cleft lip and palate repair in a single
      simultaneous procedure is a successful and, most importantly, a safe procedure,
      which enables the complete clefting condition to be repaired early and in a
      single operation.

PMID- 20036629
TI  - A new mechanism associated with compositae graft success.
AB  - It is believed that the subcutaneous fat of the skin compositae grafts acts as a
      mechanical barrier limiting vascularisation. This study aims to determine a new
      mechanism associated with compositae graft take. Ten 3*3 cm rectangular full
      thickness skin compositae grafts on the back of a pig were taken and then
      randomly changed to another place. Silicone sheets were then inserted between the
      graft and the recipient to block the direct contact of the dermis at the lateral
      surface of the graft and control the number of surface contacts. The take rate
      was measured using the digital VISITRAK((r)). The microcirculation of the graft
      was evaluated by microangiograms using a latex-lead oxide solution. There was a
      20.5% graft take in all four surface-blocked groups. The microangiograms showed
      vessel connections not only between the vessels of the dermis, but also between
      the subcutaneous fat of the graft and perforators from the basal surface of the
      wound. The subcutaneous layer does not produce a barrier but works as a
      significant source of vessel communication. Direct vessel-to-vessel anastomosis
      between the vessels of the subcutaneous fat at the graft and the basal surface of
      the recipient wound are another important mechanism for the success of compositae
      grafts.

PMID- 20036630
TI  - The toxoplasma apicoplast phosphate translocator links cytosolic and apicoplast
      metabolism and is essential for parasite survival.
AB  - Apicomplexa are unicellular eukaryotic pathogens that carry a vestigial algal
      endosymbiont, the apicoplast. The physiological function of the apicoplast and
      its integration into parasite metabolism remain poorly understood and at times
      controversial. We establish that the Toxoplasma apicoplast membrane-localized
      phosphate translocator (TgAPT) is an essential metabolic link between the
      endosymbiont and the parasite cytoplasm. TgAPT is required for fatty acid
      synthesis in the apicoplast, but this may not be its most critical function.
      Further analyses demonstrate that TgAPT also functions to supply the apicoplast
      with carbon skeletons for additional pathways and, indirectly, with energy and
      reduction power. Genetic ablation of the transporter results in rapid death of
      parasites. The dramatic consequences of loss of its activity suggest that
      targeting TgAPT could be a viable strategy to identify antiparasitic compounds.

PMID- 20036631
TI  - Vitamin C enhances the generation of mouse and human induced pluripotent stem
      cells.
AB  - Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by
      defined factors. However, the low efficiency and slow kinetics of the
      reprogramming process have hampered progress with this technology. Here we report
      that a natural compound, vitamin C (Vc), enhances iPSC generation from both mouse
      and human somatic cells. Vc acts at least in part by alleviating cell senescence,
      a recently identified roadblock for reprogramming. In addition, Vc accelerates
      gene expression changes and promotes the transition of pre-iPSC colonies to a
      fully reprogrammed state. Our results therefore highlight a straightforward
      method for improving the speed and efficiency of iPSC generation and provide
      additional insights into the mechanistic basis of the reprogramming process.

PMID- 20036632
TI  - An investigation of the occurrence and properties of the mitochondrial
      intermediate-conductance Ca2+-activated K+ channel mtKCa3.1.
AB  - The mitochondrial intermediate-conductance Ca2+-activated K+ channel mtKCa3.1 has
      recently been discovered in the HCT116 colon tumor-derived cell line, which
      expresses relatively high levels of this protein also in the plasma membrane.
      Electrophysiological recordings revealed that the channel can exhibit different
      conductance states and kinetic modes, which we tentatively ascribe to post
      translational modifications. To verify whether the localization of this channel
      in mitochondria might be a peculiarity of these cells or a more widespread
      feature we have checked for the presence of mtKCa3.1 in a few other cell lines
      using biochemical and electrophysiological approaches. It turned out to be
      present at least in some of the cells investigated. Functional assays explored
      the possibility that mtKCa3.1 might be involved in cell proliferation or play a
      role similar to that of the Shaker-type KV1.3 channel in lymphocytes, which
      interacts with outer mitochondrial membrane-inserted Bax thereby promoting
      apoptosis (Szabo, I. et al., Proc. Natl. Acad Sci. USA 105 (2008) 14861-14866). A
      specific KCa3.1 inhibitor however did not have any detectable effect on cell
      proliferation or death.

PMID- 20036633
TI  - The organellar peptidasome, PreP: a journey from Arabidopsis to Alzheimer's
      disease.
AB  - The novel peptidasome, called presequence protease, PreP, was originally
      identified and characterized in Arabidopsis thaliana as a mitochondrial matrix
      and chloroplast stroma localized metalloprotease. PreP has a function as the
      organellar peptide clearing protease and is responsible for degrading free
      targeting peptides and also other unstructured peptides up to 65 amino acid
      residues that might be toxic to organellar functions. PreP contains an inverted
      Zn-binding motif and belongs to the pitrilysin protease family. The crystal
      structure of AtPreP refined at 2.1 A demonstrated a unique totally enclosed large
      cavity of 10000 A3 that opens and closes in response to peptide binding,
      revealing a novel catalytic mechanism for proteolysis. Homologues of PreP have
      been found in yeast and human mitochondria. Interestingly, the human PreP, hPreP,
      is the protease that is responsible for clearing the human brain mitochondria
      from the toxic amyloid-beta peptide (Abeta) associated with Alzheimer's disease
      (AD). Accumulation of Abeta has been shown in the brain mitochondria from AD
      patients and mutant transgenic mice overexpressing Abeta. Here, we present a
      review of our present knowledge on structural and functional characteristics of
      PreP and discuss its mitochondrial Abeta-degrading activity in the human brain
      mitochondria in relation to AD.

PMID- 20036634
TI  - Dual functions of the human antimicrobial peptide LL-37-target membrane
      perturbation and host cell cargo delivery.
AB  - The mechanisms behind target vs. host cell recognition of the human antimicrobial
      peptide LL-37 remain ill-defined. Here, we have investigated the membrane
      disruption capacity of LL-37 using large unilamellar vesicles (LUVs) composed of
      varying mixtures of POPC, POPG and cholesterol to mimic target and host membranes
      respectively. We show that LL-37 is unable to induce leakage of entrapped calcein
      from zwitterionic POPC LUVs, whereas leakage from LUVs partially composed of POPG
      is fast and efficient. In accordance with typical antimicrobial peptide behavior,
      cholesterol diminished LL-37 induced leakage. By using linear dichroism and flow
      oriented LUVs, we found that LL-37 orients with the axis of its induced alpha
      helix parallel to the membrane surface in POPC:POPG (7:3) LUVs. In the same
      system, we also observed a time-dependent increase of the parallel alpha-helix LD
      signal on timescales corresponding to the leakage kinetics. The increased LD may
      be connected to a peptide translocation step, giving rise to mass balance across
      the membrane. This could end the leakage process before it is complete, similar
      to what we have observed. Confocal microscopy studies of eukaryotic cells show
      that LL-37 is able to mediate the cell delivery of non-covalently linked
      fluorescent oligonucleotides, in agreement with earlier studies on delivery of
      plasmid DNA (Sandgren et al., J. Biol. Chem. 279 (2004) 17951). These
      observations highlight the potential dual functions of LL-37 as an antimicrobial
      agent against bacterial target cells and a cell-penetrating peptide that can
      deliver nucleic acids into the host cells.

PMID- 20036635
TI  - Light harvesting, energy transfer and electron cycling of a native photosynthetic
      membrane adsorbed onto a gold surface.
AB  - Photosynthetic membranes comprise a network of light harvesting and reaction
      center pigment-protein complexes responsible for the primary photoconversion
      reactions: light absorption, energy transfer and electron cycling. The structural
      organization of membranes of the purple bacterial species Rb. sphaeroides has
      been elucidated in most detail by means of polarized light spectroscopy and
      atomic force microscopy. Here we report a functional characterization of native
      and untreated membranes of the same species adsorbed onto a gold surface.
      Employing fluorescence confocal spectroscopy and light-induced electrochemistry
      we show that adsorbed membranes maintain their energy and electron transferring
      functionality. Gold-adsorbed membranes are shown to generate a steady high
      photocurrent of 10 microA/cm(2) for several minutes and to maintain activity for
      up to three days while continuously illuminated. The surface-adsorbed membranes
      exhibit a remarkable functionality under aerobic conditions, even when exposed to
      light intensities well above that of direct solar irradiation. The component at
      the interface of light harvesting and electron cycling, the LH1 complex, displays
      exceptional stability, likely contributing to the robustness of the membranes.
      Peripheral light harvesting LH2 complexes show a light intensity dependent
      decoupling from photoconversion. LH2 can act as a reversible switch at low-light,
      an increased emitter at medium light and photobleaches at high light.

PMID- 20036636
TI  - Multimeric forms of the small multidrug resistance protein EmrE in anionic
      detergent.
AB  - Escherichia coli multidrug resistance protein E (EmrE) is a four transmembrane
      alpha-helix protein, and a member of the small multidrug resistance protein
      family that confers resistance to a broad range of quaternary cation compounds
      (QCC) via proton motive force. The multimeric states of EmrE protein during
      transport or ligand binding are variable and specific to the conditions of study.
      To explore EmrE multimerization further, EmrE extracted from E. coli membranes
      was solubilized in anionic detergent, sodium dodecyl sulphate (SDS), at varying
      protein concentrations. At low concentrations (</=1muM) in SDS-EmrE is monomeric,
      but upon increasing EmrE concentration, a variety of multimeric states can be
      observed by SDS-Tricine polyacrylamide gel electrophoresis (PAGE). Addition of
      the (QCC), tetraphenyl phosphonium (TPP), to SDS-EmrE samples enhanced EmrE
      multimer formation using SDS-Tricine PAGE. The relative shapes of EmrE multimers
      in SDS with or without TPP addition were determined by small angle neutron
      scattering (SANS) analysis and revealed that EmrE dimers altered in conformation
      depending on the SDS concentration. SANS analysis also revealed that relative
      shapes of larger EmrE multimers (>/=100nm sizes) altered in the presence of TPP.
      Circular dichroism spectropolarimetry displayed no differences in secondary
      structure under the conditions studied. Fluorescence spectroscopy of SDS-EmrE
      protein demonstrated that aromatic residues, Trp and Tyr, are more susceptible to
      SDS concentration than TPP addition, but both residues exhibit enhanced quenching
      at high ligand concentrations. Hence, EmrE forms various multimers in SDS that
      are influenced by detergent concentration and TPP substrate addition.

PMID- 20036637
TI  - Strong oligomerization behavior of PDGFbeta receptor transmembrane domain and its
      regulation by the juxtamembrane regions.
AB  - The platelet-derived growth factor beta-receptor (PDGFbetaR) represents an
      important subclass of receptor tyrosine kinase (RTK) thought to be activated by
      ligand-induced dimerization. Interestingly, the receptor is also activated by the
      bovine papillomavirus E5 oncoprotein, an interaction involving the transmembrane
      domains of both proteins and resulting in constitutive downstream signalling.
      This unique mode of activation along with emerging data for other RTKs raises
      important questions about the role of the PDGFbetaR transmembrane domain in
      signalling. To address this, we have investigated the murine PDGFbetaR
      transmembrane and juxtamembrane domains. We show for the first time the strong
      oligomerization behavior of PDGFbetaR transmembrane domain, forming dimers and
      trimers in natural membranes and detergents; and that these self-interactions are
      mediated by a leucine-zipper-like motif. The juxtamembrane regions are found to
      regulate these helix-helix interactions and select specifically for dimer
      formation. These data provide evidence that PDGFbetaR is able to form ligand
      independent dimers, supporting similar observations in a number of other RTK's. A
      point mutant in the PDGFbetaR juxtamembrane domain previously shown to cause
      receptor activation was studied and yielded no change in oligomerization or
      folding, suggesting (in-line with observations of the c-Kit receptor) that it may
      moderate interactions with other regions of PDGFbetaR.

PMID- 20036638
TI  - Stearic acid attenuates cholestasis-induced liver injury.
AB  - Inflammation is involved in cholestasis-induced hepatic damage. Stearic acid has
      been shown to possess anti-inflammatory potential. We assessed whether stearic
      acid has protective effects against cholestasis-related liver damage. Cholestasis
      was produced by bile duct ligation (BDL) in male Sprague-Dawley rats for 3weeks.
      Daily administration of stearic acid was started 2weeks before injury and lasted
      for 5weeks. In comparison with the control group, the BDL group showed hepatic
      damage as evidenced by elevation in serum biochemicals, ductular reaction,
      fibrosis, and inflammation. These pathophysiological changes were attenuated by
      chronic stearic acid supplementation. The anti-fibrotic effect of stearic acid
      was accompanied by reductions in alpha-smooth muscle actin-positive matrix
      producing cells and critical fibrogenic cytokine transforming growth factor beta
      1 production. Stearic acid also attenuated BDL-induced leukocyte accumulation and
      NF-kappaB activation. The data indicate that stearic acid attenuates BDL-induced
      cholestatic liver injury. The hepatoprotective effect of stearic acid is
      associated with anti-inflammatory potential.

PMID- 20036639
TI  - A murine model of sepsis following smoke inhalation injury.
AB  - Acute lung injury (ALI) by smoke inhalation with subsequent pneumonia and sepsis
      represents a major cause of morbidity and mortality in burn patients. The aim of
      the present study was to develop a murine model of ALI and sepsis to enhance the
      knowledge of mechanistic aspects and pathophysiological changes in patients with
      these injuries. In deeply anesthetized female C57BL/6 mice, injury was induced by
      four sets of cotton smoke using an inhalation chamber. Afterward, live
      Pseudomonas aeruginosa (3.2x10(7) colony-forming units) was administered
      intranasally. The indicated dose of bacteria was determined based on the results
      of a dose-response study (n=47). The following study groups were monitored for
      survival over 96h: (1) sham injury group, (2) only smoke inhalation group, (3)
      only bacteria group, and (4) smoke inhalation plus bacteria group. Each group
      included 10 mice. The survival rates were 100%, 90%, 30%, and 10%, respectively.
      The double hit injury was associated with excessive releases of pro-inflammatory
      cytokines in the plasma, and enhanced neutrophil accumulation, increased lipid
      peroxidation, and excessive formation of reactive nitrogen species in the lung.
      In mice receiving only smoke inhalation injury, no systemic cytokine release and
      increased lung tissue lipid peroxidation were observed. However, smoke alone
      significantly increased neutrophil accumulation and formation of reactive
      nitrogen species in lung tissue. In conclusion, bacterial pneumonia is
      predominantly responsible for mortality and morbidity in this novel murine model
      of smoke inhalation and pulmonary sepsis. Reactive oxygen and nitrogen species
      mediate the severity of lung injury.

PMID- 20036640
TI  - Oligomerization and insulin interactions of proinsulin C-peptide: Threefold
      relationships to properties of insulin.
AB  - Three principally different sites of action have been reported for proinsulin C
      peptide, at surface-mediated, intracellular, and extracellular locations.
      Following up on the latter, we now find that (i) mass spectrometric analyses
      reveal the presence of the C-peptide monomer in apparent equilibrium with a low
      yield set of oligomers in weakly acidic or basic aqueous solutions, even at low
      peptide concentrations (sub-muM). It further shows not only C-peptide to interact
      with insulin oligomers (known before), but also the other way around. (ii)
      Polyacrylamide gel electrophoresis of C-peptide shows detectable oligomers upon
      Western blotting. Formation of thioflavin T positive material was also detected.
      (iii) Cleavage patterns of analogues are compatible with C-peptide as a substrate
      of insulin degrading enzyme. Combined, the results demonstrate three links with
      insulin properties, in a manner reminiscent of amyloidogenic peptides and their
      chaperons in other systems. If so, peripheral C-peptide/insulin interactions,
      absolute amounts of both peptides and their ratios may be relevant to consider in
      diabetic and associated diseases.

PMID- 20036641
TI  - GABA(B) receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome.
AB  - GABA(B) receptors mediate slow inhibitory effects of the neurotransmitter gamma
      aminobutyric acid (GABA) on synaptic transmission in the central nervous system.
      They function as heterodimeric G-protein-coupled receptors composed of the seven
      transmembrane domain proteins GABA(B1) and GABA(B2), which are linked through a
      coiled-coil interaction. The ligand-binding subunit GABA(B1) is at first retained
      in the endoplasmic reticulum and is transported to the cell surface only upon
      assembly with GABA(B2). Here, we report that GABA(B1), via the coiled-coil
      domain, can also bind to soluble proteins of unknown function, that are affected
      in 22q11 deletion/DiGeorge syndrome and are therefore referred to as DiGeorge
      critical region 6 (DGCR6). In transfected neurons the GABA(B1)-DGCR6 association
      resulted in a redistribution of both proteins into intracellular clusters.
      Furthermore, the C-terminus of GABA(B2) interfered with the novel interaction,
      consistent with heterodimer formation overriding transient DGCR6-binding to
      GABA(B1). Thus, sequential coiled-coil interactions may direct GABA(B1) into
      functional receptors.

PMID- 20036642
TI  - The covalent modification of spectrin in red cell membranes by the lipid
      peroxidation product 4-hydroxy-2-nonenal.
AB  - Spectrin strengthens the red cell membrane through its direct association with
      membrane lipids and through protein-protein interactions. Spectrin loss reduces
      the membrane stability and results in various types of hereditary spherocytosis.
      However, less is known about acquired spectrin damage. Here, we showed that alpha
      and beta-spectrin in human red cells are the primary targets of the lipid
      peroxidation product 4-hydroxy-2-nonenal (HNE) by immunoblotting and mass
      spectrometry analyses. The level of HNE adducts in spectrin (particularly alpha
      spectrin) and several other membrane proteins was increased following the HNE
      treatment of red cell membrane ghosts prepared in the absence of MgATP. In
      contrast, ghost preparation in the presence of MgATP reduced HNE adduct
      formation, with preferential beta-spectrin modification and increased cross
      linking of the HNE-modified spectrins. Exposure of intact red cells to HNE
      resulted in selective HNE-spectrin adduct formation with a similar preponderance
      of HNE-beta-spectrin modifications. These findings indicate that HNE adduction
      occurs preferentially in spectrin at the interface between the skeletal proteins
      and lipid bilayer in red cells and suggest that HNE-spectrin adduct aggregation
      results in the extrusion of damaged spectrin and membrane lipids under
      physiological and disease conditions.

PMID- 20036643
TI  - Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse
      models of cancer cachexia.
AB  - Cachexia, progressive loss of fat and muscle mass despite adequate nutrition, is
      a devastating complication of cancer associated with poor quality of life and
      increased mortality. Myostatin is a potent tonic muscle growth inhibitor. We
      tested how myostatin inhibition might influence cancer cachexia using genetic and
      pharmacological approaches. First, hypermuscular myostatin null mice were
      injected with Lewis lung carcinoma or B16F10 melanoma cells. Myostatin null mice
      were more sensitive to tumor-induced cachexia, losing more absolute mass and
      proportionately more muscle mass than wild-type mice. Because myostatin null mice
      lack expression from development, however, we also sought to manipulate myostatin
      acutely. The histone deacetylase inhibitor Trichostatin A has been shown to
      increase muscle mass in normal and dystrophic mice by inducing the myostatin
      inhibitor, follistatin. Although Trichostatin A administration induced muscle
      growth in normal mice, it failed to preserve muscle in colon-26 cancer cachexia.
      Finally we sought to inhibit myostatin and related ligands by administration of
      the Activin receptor extracellular domain/Fc fusion protein, ACVR2B-Fc. Systemic
      administration of ACVR2B-Fc potently inhibited muscle wasting and protected
      adipose stores in both colon-26 and Lewis lung carcinoma cachexia, without
      affecting tumor growth. Enhanced cachexia in myostatin knockouts indicates that
      host-derived myostatin is not the sole mediator of muscle wasting in cancer. More
      importantly, skeletal muscle preservation with ACVR2B-Fc establishes that
      targeting myostatin-family ligands using ACVR2B-Fc or related molecules is an
      important and potent therapeutic avenue in cancer cachexia.

PMID- 20036644
TI  - The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1-23) and
      amyloid beta-peptide (Abeta1-40): Implications for Bri2 effects on processing of
      amyloid precursor protein and Abeta aggregation.
AB  - In Alzheimer's disease the amyloid beta-peptide (Abeta) aggregates in brain
      tissue and arteries. Abeta is proteolytically cleaved out from amyloid precursor
      protein (APP) by different secretases. Recently, the transmembrane protein
      ITM2B/Bri2, which is expressed in neurons and associated with familial British
      and Danish dementia, was shown to inhibit APP processing in transfected cells as
      well as in transgenic mice. Several mechanisms by which Bri2 can interfere with
      Abeta production and aggregation have been proposed. Herein, we studied
      recombinant human Bri2 (residues 90-236) containing the extracellular Brichos
      domain without the ABri23 peptide. Bri2(90-236) binds to ABri23, which suggests
      that these two parts interact during Bri2 biosynthesis, in line with proposed
      functions of Brichos domains in other proteins. Moreover, Bri2(90-236) binds
      Abeta1-40 and inhibits its aggregation and fibril formation. These data suggest a
      model for how the processing of Bri2 and APP are interrelated.

PMID- 20036645
TI  - Class A scavenger receptor promotes osteoclast differentiation via the enhanced
      expression of receptor activator of NF-kappaB (RANK).
AB  - Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, and
      their differentiation depends on macrophage colony-stimulating factor (M-CSF) and
      receptor activator nuclear factor kappa B (RANK) ligand. Class A scavenger
      receptor (SR-A) is one of the principal functional molecules of macrophages, and
      its level of expression declines during osteoclast differentiation. To
      investigate the role of SR-A in osteoclastogenesis, we examined pathological
      changes in femoral bone and the expression levels of osteoclastogenesis-related
      molecules in SR-A(-/-) mice. The femoral osseous density of SR-A(-/-) mice was
      higher than that of SR-A(+/+) mice, and the number of multinucleated osteoclasts
      was significantly decreased. An in vitro differentiation assay revealed that the
      differentiation of multinucleated osteoclasts from bone marrow-derived progenitor
      cells is impaired in SR-A(-/-) mice. Elimination of SR-A did not alter the
      expression level of the M-CSF receptor, c-fms; however, the expression levels of
      RANK and RANK-related osteoclast-differentiation molecules such as nuclear factor
      of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and
      microphthalmia-associated transcription factor (MITF) significantly decreased.
      Furthermore, acetylated low-density lipoprotein (AcLDL), an SR-A ligand,
      significantly increased the expression level of RANK and MITF during osteoclast
      differentiation. These data indicate that SR-A promotes osteoclastogenesis via
      augmentation of the expression level of RANK and its related molecules.

PMID- 20036647
TI  - Leptin modulates noradrenaline release in the paraventricular nucleus and plasma
      oxytocin levels in female rats: a microdialysis study.
AB  - The neural control and mutual interrelationships among individual factors
      involved in the regulation of food intake and simultaneously related to
      reproduction are far from being understood. We have suggested that at least some
      of the effects of orexigenic and anorexigenic peptides might be mediated via
      noradrenaline release in the paraventricular nucleus (PVN). The main hypothesis
      was that leptin has an inhibitory action on oxytocin secretion and hypothalamic
      release of noradrenaline. Non-pregnant female rats in their diestrus were
      subjected to cannulation of the carotid artery and a microdialysis procedure with
      the probes in the hypothalamic PVN. Intra-arterial administration of
      cholecystokinin-8 (CCK) at the dose of 50 mg/kg was used to induce oxytocin and
      noradrenaline release. Leptin (10 mg/5 ml) was intracerebroventricularly injected
      in addition to CCK. Blood and microdialysis samples were collected at 20-min
      intervals for 80 min. Central administration of leptin significantly reduced both
      plasma oxytocin and hypothalamic noradrenaline responses to CCK at 20 min
      following the treatments. In conclusion, leptin may inhibit oxytocin secretion by
      lowering noradrenergic neurotransmission in the PVN. The modulator effect of
      leptin on noradrenaline release in the PVN may be related to feeding behavior.

PMID- 20036646
TI  - Susceptibility to acetaminophen (APAP) toxicity unexpectedly is decreased during
      acute viral hepatitis in mice.
AB  - Acetaminophen (APAP) hepatotoxicity results from cytochrome P450 metabolism of
      APAP to the toxic metabolite, n-acetyl-benzoquinone imine (NAPQI), which reacts
      with cysteinyl residues to form APAP adducts and initiates cell injury. As APAP
      is commonly used during viral illnesses there has been concern that APAP injury
      may be additive to that of viral hepatitis, leading physicians to advise against
      its use in such patients; this has not been investigated experimentally. We
      infected C57BL/6 male mice with replication-deficient adenovirus to produce
      moderately severe acute viral hepatitis and observed that APAP doses that were
      hepatotoxic or lethal in control mice produced neither death nor additional
      increase in serum ALT when administered to infected mice at the peak of virus
      induced liver injury. Moreover, the concentration of hepatic APAP-protein adducts
      formed in these mice was only 10% that in control mice. Protection from APAP
      hepatotoxicity also was observed earlier in the course of infection, prior to the
      peak virus-induced ALT rise. Hepatic glutathione limits APAP-protein adduct
      formation but glutathione levels were similar in control and infected mice.
      Cyp1a2 (E.C. 1.14.14.1) and Cyp2e1 (E.C. 1.14.13.n7) mRNA expression decreased by
      3 days post-infection and hepatic Cyp2e1 protein levels were reduced almost 90%
      at 7 days, when adduct formation was maximally inhibited. In vitro, hepatocytes
      from virally infected mice also were resistant to APAP-induced injury but
      sensitive to NAPQI. Rather than potentiating APAP-induced liver injury, acute
      viral hepatitis in this model resulted in selective down-regulation of APAP
      metabolizing P450s in liver and decreased the risk of APAP hepatotoxicity.

PMID- 20036648
TI  - Gene expression in benzene-exposed workers by microarray analysis of peripheral
      mononuclear blood cells: induction and silencing of CYP4F3A and regulation of DNA
      dependent protein kinase catalytic subunit in DNA double strand break repair.
AB  - Benzene causes hematotoxicity and leukemia in humans. To analyze benzene-caused
      aberrant gene expression, we examined differential gene expression by microarray
      analysis of peripheral mononuclear blood cells from seven workers diagnosed with
      benzene poisoning and seven matched controls. Twenty-two genes were found up
      regulated and 18 down-regulated in benzene patients compared with controls. Here
      we report the characterization of two benzene-regulated genes. CYP4F3A, which
      encodes the leukotriene B(4) (LTB(4)) omega-hydroxylase, is important for
      inactivation of LTB(4) in neutrophils. CYP4F3A mRNA was found elevated in all
      patients; moreover, CYP4F3A mRNA and protein were induced by benzene metabolite
      phenol in HL-60 and K562 cells as well as ex vivo in human peripheral
      neutrophils. Silencing of CYP4F3A in HL-60 cells by lentiviral delivery of
      CYP4F3A-specific siRNA reduced cell survival to 56%, 44%, 22%, 14%, and 3% at 3,
      4, 5, 6, and 7 days, respectively; the results suggest that CYP4F3A is a critical
      positive regulator of HL-60 proliferation. DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs) regulates non-homologous end joining (NHEJ) in DNA double
      strand break (DSB) repair. DNA-PKcs mRNA was found consistently increased in the
      patients and DNA-PKcs mRNA and protein were induced by hydroquinone in HL-60
      cells. In a DSB model, hydroquinone induced the formation of gamma-H2AX foci, a
      marker of DSBs, in HL-60 cells. The findings indicate that hydroquinone induces
      DSBs and induction correlates with elevated levels of DNA-PKcs and NHEJ. Similar
      results were obtained in K562 cells treated with phenol. Since NHEJ is error
      prone, induction of DNA-PKcs and NHEJ may contribute to mutagenesis and leukemia
      by benzene. To our knowledge, the study demonstrated for the first time that
      benzene and metabolites induce CYP4F3A and DNA-PKcs both in vivo and in vitro.
      Induction of the genes may play a role in the pathogenesis of benzene
      hematotoxicity and serve as biomarkers of benzene exposure.

PMID- 20036649
TI  - Exposure to benzene in various susceptible populations: co-exposures to 1,3
      butadiene and PAHs and implications for carcinogenic risk.
AB  - Exposure to benzene in human populations can occur in various work-related
      settings in which benzene is used or produced, or from traffic emissions
      resulting from incomplete combustion of fossil fuel, or from other sources. Two
      scenarios of benzene exposure were studied in 4 susceptible groups in Thailand.
      The first scenario is work-related exposures primarily to benzene, with the study
      subjects consisting of petrochemical laboratory workers and gasoline service
      station attendants, who are exposed at levels of 78.32 and 360.84 microg/m(3),
      respectively. The second scenario is traffic-related exposure and exposure to
      incense smoke, where co-exposures to other pollutants occurs, with the study
      groups consisting of school children attending schools in the city center and
      exposed to traffic emissions, and temple workers exposed to incense smoke. The
      individual benzene exposure levels were approximately 19.38 microg/m(3) in city
      school children and 45.90 microg/m(3) in temple workers. Co-exposures to 1,3
      butadiene and polycyclic aromatic hydrocarbons (PAHs) generated from the same
      sources occurred in the second exposure scenario. 8-OHdG, DNA strand breaks and
      DNA repair capacity were measured as biomarkers of early effects of carcinogenic
      compound exposure. Petrochemical laboratory workers and gasoline service stations
      attendants had significantly higher levels of DNA strand breaks and significantly
      lower DNA repair capacity compared to controls, while gasoline service station
      attendants also had significantly higher levels of 8-OHdG than controls. City
      school children had significantly higher levels of PAH-DNA adducts, 8-OHdG, and
      DNA strand breaks and significantly lower levels of DNA repair capacity compared
      to rural children. Temple workers also had significantly higher levels of 8-OHdG
      and DNA strand breaks and significantly lower levels of DNA repair capacity
      compared to controls. In all of the study groups, the levels of benzene exposure
      correlated significantly with 8-OHdG levels, DNA strand breaks, and DNA repair
      capacity. In school children, PAH levels also correlated significantly with 8
      OHdG levels, DNA strand breaks and DNA repair capacity. In temple workers, 1,3
      butadiene levels correlated significantly with 8-OHdG and DNA strand breaks, but
      not with DNA repair capacity, while in the school children they did not correlate
      significantly with 8-OHdG or DNA strand breaks, and correlated marginally
      significantly with DNA repair capacity (deletions per metaphase). Multivariate
      regression analysis identified total PAHs concentrations converted to B[a]P
      equivalents as the only factor significantly affecting 8-OHdG levels, and total
      PAHs concentrations converted to B[a]P equivalents, as well as 1,3-butadiene
      concentrations as the factors significantly affecting DNA repair capacity in the
      school children. PAHs concentration was identified as the factor most
      significantly affecting DNA strand breaks in temple workers, followed by benzene
      concentrations, while DNA repair capacity was also significantly influenced by
      PAHs concentrations.

PMID- 20036651
TI  - Assessment of neuromuscular dysfunction during poisoning by organophosphorus
      compounds.
AB  - Dysfunction of respiratory muscles is a life-threatening complication in
      poisoning by organophosphorus compounds (OPs). It is both of central and
      peripheral origin due to impaired cholinergic signalling upon inhibition of
      acetylcholinesterase (AChE). The dysfunction at neuromuscular synapses is not
      amenable to anticholinergics and remains a therapeutic challenge. Thus, a clear
      understanding of the distinct mechanisms occurring at neuromuscular synapses is
      decisive for the development and improvement of therapeutic strategies,
      particularly with nerve agent poisoning, where clinical studies are prevented by
      ethical considerations. Using red blood cell AChE, the kinetics of OP induced
      inhibition, aging, and spontaneous and oxime-induced reactivation have been
      elucidated. In a dynamically working in vitro model with real-time determination
      of membrane-bound AChE, it was shown that the kinetic constants derived from
      erythrocyte AChE are comparable to muscle AChE in a given species. To assess,
      whether kinetic considerations of AChE activity are relevant for the
      neuromuscular function, organotypic spinal cord-skeletal muscle cocultures have
      been established. In this model neostigmine and VX affected neuromuscular
      transmission as anticipated from their known actions on AChE. Also oxime-induced
      restoration of the neuromuscular transmission was observed. These findings were
      confirmed by functional studies on diaphragm muscles of various species with
      determination of muscle force generation upon phrenic nerve or indirect
      electrical field stimulation techniques. Investigations with human intercostal
      muscles are in progress to assess the conditions in human tissue. The results
      obtained with paraoxon favourably correlate with data from clinical findings of
      parathion-poisoned patients where the correlation of neuromuscular transmission
      with the activity of erythrocyte AChE could be established. In conclusion, a
      variety of methods are available to follow the microscopic reactions occurring at
      the synaptic level. Due to the lack of clinical data with different OPs, e.g.
      nerve agents, well designed animal experiments, reflecting the human situation as
      close as possible, are indispensable for the development of new drugs against the
      deleterious OP effects.

PMID- 20036650
TI  - The fate of benzene-oxide.
AB  - Metabolism is a prerequisite for the development of benzene-mediated
      myelotoxicity. Benzene is initially metabolized via cytochromes P450 (primarily
      CYP2E1 in liver) to benzene-oxide, which subsequently gives rise to a number of
      secondary products. Benzene-oxide equilibrates spontaneously with the
      corresponding oxepine valence tautomer, which can ring open to yield a reactive
      alpha,beta-unsaturated aldehyde, trans-trans-muconaldehyde (MCA). Further
      reduction or oxidation of MCA gives rise to either 6-hydroxy-trans-trans-2,4
      hexadienal or 6-hydroxy-trans-trans-2,4-hexadienoic acid. Both MCA and the
      hexadienal metabolite are myelotoxic in animal models. Alternatively, benzene
      oxide can undergo conjugation with glutathione (GSH), resulting in the eventual
      formation and urinary excretion of S-phenylmercapturic acid. Benzene-oxide is
      also a substrate for epoxide hydrolase, which catalyzes the formation of benzene
      dihydrodiol, itself a substrate for dihydrodiol dehydrogenase, producing
      catechol. Finally, benzene-oxide spontaneously rearranges to phenol, which
      subsequently undergoes either conjugation (glucuronic acid or sulfate) or
      oxidation. The latter reaction, catalyzed by cytochromes P450, gives rise to
      hydroquinone (HQ) and 1,2,4-benzene triol. Co-administration of phenol and HQ
      reproduces the myelotoxic effects of benzene in animal models. The two diphenolic
      metabolites of benzene, catechol and HQ undergo further oxidation to the
      corresponding ortho-(1,2-), or para-(1,4-)benzoquinones (BQ), respectively.
      Trapping of 1,4-BQ with GSH gives rise to a variety of HQ-GSH conjugates, several
      of which are hematotoxic when administered to rats. Thus, benzene-oxide gives
      rise to a cascade of metabolites that exhibit biological reactivity, and that
      provide a plausible metabolic basis for benzene-mediated myelotoxicity. Benzene
      oxide itself is remarkably stable, and certainly capable of translocating from
      its primary site of formation in the liver to the bone marrow. However, therein
      lies the challenge, for although there exists a plethora of information on the
      metabolism of benzene, and the fate of benzene-oxide, there is a paucity of data
      on the presence, concentration, and persistence of benzene metabolites in bone
      marrow. The major metabolites in bone marrow of mice exposed to 50 ppm
      [(3)H]benzene are muconic acid, and glucuronide and/or sulfate conjugates of
      phenol, HQ, and catechol. Studies with [(14)C/(13)C]benzene revealed the presence
      in bone marrow of protein adducts of benzene-oxide, 1,4-BQ, and 1,4-BQ, the
      relative abundance of which was both dose and species dependent. In particular,
      histones are bone marrow targets of [(14)C]benzene, although the identity of the
      reactive metabolite(s) giving rise to these adducts remain unknown. Finally,
      hematotoxic HQ-GSH conjugates are present in the bone marrow of rats receiving
      the HQ/phenol combination. In summary, although the fate of benzene-oxide is
      known in remarkable detail, coupling this information to the site, and mechanism
      of action, remains to be established.

PMID- 20036652
TI  - Vascular endothelial growth factor (VEGF) regulates cranial neural crest
      migration in vivo.
AB  - The neural crest is an excellent model to study embryonic cell migration, since
      cell behaviors can be studied in vivo with advanced optical imaging and molecular
      intervention. What is unclear is how molecular signals direct neural crest cell
      (NCC) migration through multiple microenvironments and into specific targets.
      Here, we tested the hypothesis that the invasion of cranial NCCs, specifically
      the rhombomere 4 (r4) migratory stream into branchial arch 2 (ba2), is due to
      chemoattraction through neuropilin-1-vascular endothelial growth factor (VEGF)
      interactions. We found that the spatio-temporal expression pattern of VEGF in the
      ectoderm correlated with the NCC migratory front. RT-PCR analysis of the r4
      migratory stream showed that ba2 tissue expressed VEGF and r4 NCCs expressed VEGF
      receptor 2. When soluble VEGF receptor 1 (sVEGFR1) was injected distal to the r4
      migratory front, to bind up endogenous VEGF, NCCs failed to completely invade
      ba2. Time-lapse imaging revealed that cranial NCCs were attracted to ba2 tissue
      or VEGF sources in vitro. VEGF-soaked beads or VEGF-expressing cells placed
      adjacent to the r4 migratory stream caused NCCs to divert from stereotypical
      pathways and move towards an ectopic VEGF source. Our results suggest a model in
      which NCC entry and invasion of ba2 is dependent on chemoattractive signaling
      through neuropilin-1-VEGF interactions.

PMID- 20036653
TI  - Kinesin-dependent transport results in polarized migration of the nucleus in
      oocytes and inward movement of yolk granules in meiotic embryos.
AB  - During female meiosis, meiotic spindles are positioned at the oocyte cortex to
      allow expulsion of chromosomes into polar bodies. In C. elegans, kinesin
      dependent translocation of the entire spindle to the cortex precedes dynein
      dependent rotation of one spindle pole toward the cortex. To elucidate the role
      of kinesin-1 in spindle translocation, we examined the localization of kinesin
      subunits in meiotic embryos. Surprisingly, kinesin-1 was not associated with the
      spindle and instead was restricted to the cytoplasm in the middle of the embryo.
      Yolk granules moved on linear tracks, in a kinesin-dependent manner, away from
      the cortex, resulting in their concentration in the middle of the embryo where
      the kinesin was concentrated. These results suggest that cytoplasmic microtubules
      might be arranged with plus ends extending inward, away from the cortex. This
      microtubule arrangement would not be consistent with direct transport of the
      meiotic spindle toward the cortex by kinesin-1. In maturing oocytes, the nucleus
      underwent kinesin-dependent migration to the future site of spindle attachment at
      the anterior cortex. Thus the spindle translocation defect observed in kinesin-1
      mutants may be a result of failed nuclear migration, which places the spindle too
      far from the cortex for the spindle translocation mechanism to function.

PMID- 20036654
TI  - Anatomy of the human corneal innervation.
AB  - The anatomy of the human corneal innervation has been the subject of much
      investigation; however, a comprehensive description remains elusive. The purpose
      of the present study was to provide a detailed description of the human corneal
      innervation using a novel approach involving immunohistochemically stained
      anterior-cornea whole mounts. Sixteen donor corneas aged 19-78 years were cut
      with a 6.0 mm trephine into a central plug and two peripheral rims. Each specimen
      was sectioned serially on a cryostat to produce several 100 microm-thick stromal
      sections and a 100-140 microm-thick anterior-cornea whole mount that contained
      the entire corneal epithelium and much of the anterior stroma. The corneal
      innervation was stained with a primary antibody against beta neurotubulin and
      subjected to rigorous quantitative and qualitative analyses. The results showed
      that a mean of 71.3 +/- 14.3, uniformly spaced, main stromal nerve bundles
      entered the cornea at the corneoscleral limbus. The bundles averaged 20.3 +/- 7.0
      microm in diameter, were separated by a mean spacing of 0.49 +/- 0.40 mm, and
      entered the cornea at a mean distance of 293 +/- 106 microm from the ocular
      surface. Each stromal bundle gave rise through repetitive branching to a
      moderately dense midstromal plexus and a dense subepithelial plexus (SEP). The
      SEP was comprised of modest numbers of straight and curvilinear nerves, most of
      which penetrated Bowman's membrane to supply the corneal epithelium, and a more
      abundant and anatomically complex population of tortuous, highly anastomotic
      nerves that remained largely confined in their distribution to the SEP. SEP
      density and anatomical complexity varied considerably among corneas and was less
      dense and patchier in the central cornea. A mean of 204 +/- 58.5 stromal nerves
      penetrated Bowman's membrane to supply the central 10 mm of corneal epithelium
      (2.60 nerves/mm(2)). The density of Bowman's membrane penetrations was greater
      peripherally than centrally. After entering the epithelium, stromal nerves
      branched into groups of up to twenty subbasal nerve fibers known as epithelial
      leashes. Leashes in the central and intermediate cornea anastomosed extensively
      to form a dense, continuous subbasal nerve plexus, while leashes in the
      peripheral cornea demonstrated fewer anastomoses and were less complex
      anatomically. Viewed in its entirety, the subbasal nerve plexus formed a gentle,
      whorl-like assemblage of long curvilinear subbasal fibers, 1.0-8.0 mm in length,
      that converged on an imaginary seam or gentle spiral (vortex) approximately 2.51
      +/- 0.23 mm inferonasal to the corneal apex. Mean subbasal nerve fiber density
      near the corneal apex was 45.94 +/- 5.20 mm/mm(2) and mean subbasal and
      interconnecting nerve fiber diameters in the same region were 1.51 +/- 0.74
      microm and 0.69 +/- 0.26 microm, respectively. Intraepithelial terminals
      originated exclusively as branches of subbasal nerves and terminated in all
      epithelial layers. Nerve terminals in the wing and squamous cell layers were
      morphologically diverse and ranged in total length from 9 to 780 microm. The
      suprabasal layers of the central corneal epithelium contained approximately 605.8
      terminals/mm(2). The results of this study provide a detailed, comprehensive
      description of human corneal nerve architecture and density that extends and
      refines existing accounts. An accurate, detailed model of the normal human
      corneal innervation may predict or help to understand the consequences of corneal
      nerve damage during refractive, cataract and other ocular surgeries.

PMID- 20036655
TI  - Channelrhodopsin-2 gene transduced into retinal ganglion cells restores
      functional vision in genetically blind rats.
AB  - To test the hypothesis that transduction of the channelrhodopsin-2 (ChR2) gene, a
      microbial-type rhodopsin gene, into retinal ganglion cells of genetically blind
      rats will restore functional vision, we recorded visually evoked potentials and
      tested the experimental rats for the presence of optomotor responses. The N
      terminal fragment of the ChR2 gene was fused to the fluorescent protein Venus and
      inserted into an adeno-associated virus to make AAV2-ChR2V. AAV2-ChR2V was
      injected intravitreally into the eyes of 6-month-old dystrophic RCS (rdy/rdy)
      rats. Visual function was evaluated six weeks after the injection by recording
      visually evoked potentials (VEPs) and testing optomotor responses. The expression
      of ChR2V in the retina was investigated histologically. We found that VEPs could
      not be recorded from 6-month-old dystrophic RCS rats that had not been injected
      with AAV2-ChR2V. In contrast, VEPs were elicited from RCS rats six weeks after
      injection with AAV2-ChR2V. The VEPs were recorded at stimulation rates <20Hz,
      which was the same as that of normal rats. Optomotor responses were also
      significantly better after the AAV2-ChR2V injection. Expression of ChR2V was
      observed mainly in the retinal ganglion cells. These findings demonstrate that
      visual function can be restored in blind rats by transducing the ChR2V gene into
      retinal ganglion cells.

PMID- 20036656
TI  - Screening of Swiss hot spring resorts for potentially pathogenic free-living
      amoebae.
AB  - Free-living amoebae (FLA) belonging to Acanthamoeba spp., Naegleria fowleri,
      Balamuthia mandrillaris, and Sappinia pedata are known to cause infections in
      humans and animals leading to severe brain pathologies. Worldwide, warm aquatic
      environments have been found to be suitable habitats for pathogenic FLA. The
      present study reports on screening for potentially pathogenic FLA in four hot
      spring resorts in Switzerland. Water samples were taken from water filtration
      units and from the pools, respectively. Amoebae isolated from samples taken
      during, or before, the filtration process were demonstrated to be morphologically
      and phylogenetically related to Stenoamoeba sp., Hartmannella vermiformis,
      Echinamoeba exundans, and Acanthamoeba healyi. With regard to the swimming pools,
      FLA were isolated only in one resort, and the isolate was identified as non
      pathogenic and as related to E. exundans. Further investigations showed that the
      isolates morphologically and phylogenetically related to A. healyi displayed a
      pronounced thermotolerance, and exhibited a marked in vitro cytotoxicity upon 5
      day exposure to murine L929 fibroblasts. Experimental intranasal infection of
      Rag2-immunodeficient mice with these isolates led to severe brain pathologies,
      and viable trophozoites were isolated from the nasal mucosa, brain tissue, and
      lungs post mortem. In summary, isolates related to A. healyi were suggestive of
      being potentially pathogenic to immunocompromised persons. However, the presence
      of these isolates was limited to the filtration units, and an effective threat
      for health can therefore be excluded.

PMID- 20036657
TI  - Plasmodium falciparum: in vitro interaction of quassin and neo-quassin with
      artesunate, a hemisuccinate derivative of artemisinin.
AB  - Quassia amara L. (Family Simaroubaceae) is known to have several medicinal
      properties including the activity against malaria. An HPLC method was employed
      for purification of the biologically active quassinoids; quassin (Q) and neo
      quassin (NQ), further characterized by MALDI-TOF analyses. Purified Q, NQ and the
      crude bark extract (S1) along with artesunate (AS) were studied for their in
      vitro anti-plasmodial activity. The in vivo toxicity studies at intraperitoneal
      doses with higher concentrations of the crude bark extract (S1) in Balb/C mice
      ruled out the apprehension of toxicity. Interaction studies between the test
      compounds among themselves (Q+NQ) and individually with artesunate (AS+Q, AS+NQ),
      were carried out in vitro at four ratios (1:5, 1:2, 2:1 and 5:1) on chloroquine
      sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium
      falciparum. The crude bark extracts of Q. amara exhibited higher P. falciparum
      inhibitory activity (IC(50)=0.0025 microg/ml) as compared to that of the isolated
      compounds, quassin (IC(50)=0.06 microg/ml, 0.15 microM), neo-quassin (IC(50)=0.04
      microg/ml, 0.1 microM) and also to the positive control, artesunate (IC(50)=0.02
      microg/ml, 0.05 microM). The in vitro drug interaction study revealed the
      compounds, quassin and neo-quassin to be additive to each other. At lower ratios,
      artesunate was found to be a potential combination partner with both the
      compounds. It was interesting to note that none of the combinations exhibited
      antagonistic interactions. This phenomenon offers the opportunity for further
      exploration of novel therapeutic concentrations and combinations.

PMID- 20036658
TI  - Autophagy in the fission yeast Schizosaccharomyces pombe.
AB  - Autophagy is a non-selective degradation process in eukaryotic cells. The genome
      sequence of the fission yeast Schizosaccharomyces pombe has revealed that many of
      the genes required for autophagy are common between the fission yeast and budding
      yeast, suggesting that the basic machinery of autophagy is conserved between
      these species. Autophagy in fission yeast is specifically induced by nitrogen
      starvation based on monitoring a GFP-Atg8p marker. Upon nitrogen starvation,
      fission yeast cells exit the vegetative cell cycle and initiate sexual
      differentiation to produce spores. Most of the nitrogen used for de novo protein
      synthesis during sporulation derives from the autophagic protein degradation
      system. This review focuses on the recent advances in the role of autophagy in
      fission yeast.

PMID- 20036659
TI  - Membrane rafting: from apical sorting to phase segregation.
AB  - In this review we describe the history of the development of the raft concept for
      membrane sub-compartmentalization. From its early beginnings as a mechanism for
      apical sorting in epithelial cells the concept has evolved to a general principle
      for membrane organisation. After a shaky start with crude methodology based on
      detergent extraction the field has become increasingly sophisticated, employing a
      host of different methods that support the existence of dynamic raft domains in
      membranes. These are composed of fluctuating nanoscale assemblies of
      sphingolipid, cholesterol and proteins that can be stabilized to coalesce,
      forming platforms that function in membrane signalling and trafficking.

PMID- 20036660
TI  - CLC transport proteins in plants.
AB  - Nitrate compartmentalization in intracellular organelles has been long recognized
      as critical for plant physiology but the molecular identity of the proteins
      involved remained unclear for a long time. In Arabidopsis thaliana, AtClC-a has
      been recently shown to be a NO(3)(-)/H(+) antiporter critical for nitrate
      transport into the vacuoles. AtClC-a is a member of the CLC protein family, whose
      animal and bacterial members, comprising both channels and H(+)-coupled
      antiporters, have been previously implicated exclusively in Cl(-) transport.
      Despite the different NO(3)(-) over Cl(-) selectivity of AtClC-a compared to the
      other CLC antiporters, it has similar transport properties. Other CLC homologues
      have been cloned in Arabidopsis, tobacco, rice and soybean.

PMID- 20036661
TI  - The urokinase receptor: focused cell surface proteolysis, cell adhesion and
      signaling.
AB  - Plasma membrane urokinase-type plasminogen activator (uPA)-receptor (uPAR) is a
      GPI-anchored protein that binds with high-affinity and activates the serine
      protease uPA, thus regulating proteolytic activity at the cell surface. In
      addition, uPAR is a signaling receptor that often does not require its protease
      ligand or its proteolytic function. uPAR is highly expressed during tissue
      reorganization, inflammation, and in virtually all human cancers. Since its
      discovery, in vitro and in vivo models, as well as retrospective clinical studies
      have shown that over-expression of components of the uPA/uPAR-system correlates
      with increased proliferation, migration, and invasion affecting the malignant
      phenotype of cancer. uPAR regulates the cells-extracellular matrix interactions
      promoting its degradation and turnover through the plasminogen activation
      cascade.

PMID- 20036662
TI  - Stability of lipid domains.
AB  - Membranes with simple lipid composition exhibit complex phase behavior. Ordered
      and disordered liquid phases can coexist in cholesterol-containing membranes with
      lipid compositions resembling biological membranes and at physiological
      temperatures. Research during the last years suggests that these lipid domains
      play a role in the organization of biological membranes. Understanding the
      principles that govern the formation and stability of lipid domains is of great
      importance to build a model that properly describes membrane structure and
      function. In this review, we describe the current knowledge of the chemical and
      physical basis of lipid domains and its application to biological membranes.

PMID- 20036663
TI  - Structure of the GTPase and GDI domains of FeoB, the ferrous iron transporter of
      Legionella pneumophila.
AB  - Prokaryotic pathogens have developed specialized mechanisms for efficient uptake
      of ferrous iron (Fe(2+)) from the host. In Legionella pneumophila, the causative
      agent of Legionnaires' disease, the transmembrane GTPase FeoB plays a key role in
      Fe(2+) acquisition and virulence. FeoB consists of a membrane-embedded core and
      an N-terminal, cytosolic region (NFeoB). Here, we report the crystal structure of
      NFeoB from L. pneumophila, revealing a monomeric protein comprising two separate
      domains with GTPase and guanine-nucleotide dissociation inhibitor (GDI)
      functions. The GDI domain displays a novel fold, whereas the overall structure of
      the GTPase domain resembles that of known G domains but is in the rarely observed
      nucleotide-free state.

PMID- 20036664
TI  - Photodynamic antimicrobial activity of avian eggshell pigments.
AB  - Pigmentation in avian eggshells appears to be associated with shell strength,
      temperature regulation, and camouflage. The pigments found in eggshells are
      mainly porphyrins, which have been utilized therapeutically as photosensitizers.
      Here, we examined the photoinactivation of gram-positive (Staphylococcus aureus,
      Bacillus cereus) and gram-negative bacteria (Escherichia coli, Salmonella
      enteritidis) by hen eggshells and their pigments. The results indicated that
      eggshells have a light-dependent antimicrobial activity against gram-positive,
      but not gram-negative, bacteria. Our results indicate the possibility that the
      natural pigments used therapeutically have evolved in nature as a defence system.

PMID- 20036665
TI  - Roles of the intramolecular regions of FE65 in its trans-accumulation and in p53
      stabilization in the nuclear matrix of osmotically stressed cells.
AB  - The neural adaptor protein FE65 interacts with the amyloid beta-protein precursor
      (APP). In osmotically stressed cells, the membrane APP-tethered FE65 is released
      into the cytoplasm and translocates to the nuclear matrix, where it stabilizes
      p53 via a non-canonical pathway. In this study, we found that the second
      phosphotyrosine interaction domain (PI2) of FE65 mediated its trans-accumulation
      in the nuclear matrix of osmotically stressed cells. The carboxyl-terminal half
      of FE65, which contains the PI2 domain, failed to stabilize p53, suggesting that
      the amino-terminal half of the protein plays an important role in the
      stabilization of p53 in osmotically stressed cells.

PMID- 20036666
TI  - Interaction of mitochondrial potassium channels with the permeability transition
      pore.
AB  - Three types of potassium channels cooperate with the permeability transition pore
      (PTP) in the inner mitochondrial membranes of various tissues, mtK((ATP)), mtBK,
      and mtKv1.3. While the latter two share similarities with their plasma membrane
      counterparts, mtK((ATP)) exhibits considerable differences with the plasma
      membrane K((ATP))-channel. One important function seems to be suppression of
      release of proapototic substances from mitochondria through the PTP. Open
      potassium channels tend to keep the PTP closed thus acting as antiapoptotic.
      Nevertheless, in their mode of action there are considerable differences among
      them. This review introduces three K(+)-channels and the PTP, and discusses known
      facts about their interaction.

PMID- 20036667
TI  - Endocrine patterns of the estrous cycle and pregnancy of wildebeest in the
      Serengeti ecosystem.
AB  - Despite the importance of the western white-bearded wildebeest (Connochaetes
      taurinus mearnsi) to the Serengeti-Mara ecosystem, surprisingly little is known
      about the reproductive physiology of this keystone species. A longitudinal, non
      invasive endocrine study was conducted on female wildebeest captured from the
      Serengeti-Mara migration and maintained for approximately 16 months in large
      fenced enclosures within the species' natural range. An intact bull was
      introduced to a female subgroup (n=5), while remaining females (n=10) were
      unexposed to a male. Fecal progestagen patterns reflected ovarian activity and
      pregnancy. In non-pregnant animals, luteal and inter-luteal baseline progestagen
      values differed (p<0.001) over time, thereby allowing identification of recurrent
      estrous cycles. The average durations of the luteal phase, estrous cycle,
      gestation, and post-partum anestrus were 14.3+/-0.5, 22.6+/-1.0, 240.8+/-11.7,
      and 104.1+/-15.6 d, respectively. Annual reproductive patterns indicated a
      distinctive period of ovarian activity that extended from 13 May through 3
      December (203.5+/-29.9 d) with all unmated females displaying from one to 14
      estrous cycles. Progestagens were higher (p <0.001) in pregnant (n=4) than non
      pregnant (n=10) cows. These data (1) reveal the value of fecal hormone monitoring
      for establishing the first ever endocrine profiles of female wildebeest in semi
      free-living conditions in their native range, and (2) indicate that the species
      is a seasonal breeder that is polyestrous and a spontaneous ovulator.

PMID- 20036668
TI  - Similarity in ectoparasite faunas of Palaearctic rodents as a function of host
      phylogenetic, geographic or environmental distances: which matters the most?
AB  - Different host species harbour parasite faunas that are anywhere from very
      similar to very different in species composition. A priori, the similarity in the
      parasite faunas of any two host species should decrease with increases in either
      the phylogenetic distance, the distinctness of the environments occupied or the
      geographical distance between these hosts. We tested these predictions using
      extensive data on the faunas of fleas (Insecta: Siphonaptera) and gamasid mites
      (Acari: Parasitiformes) parasitic on rodents across the Palaearctic. For each
      pair of host species, we computed the similarity in parasite faunas based on both
      species composition as well as the phylogenetic and/or taxonomic distinctness of
      parasite species. Phylogenetic distances between hosts were based on patristic
      distances through a rodent phylogeny, geographic distances were computed from
      geographic range data, and environmental dissimilarity was measured from the
      average climatic and vegetation scores of each host range. Using multiple
      regressions on distance matrices to assess the separate explanatory power of each
      of the three dependent variables, environmental dissimilarity between the ranges
      of host species emerged as the best predictor of dissimilarity between parasite
      faunas, especially for fleas; in the case of mites, phylogenetic distance between
      host species was also important. A closer look at the data indicates that the
      flea and mite faunas of two hosts inhabiting different environments are always
      different, whilst hosts living in similar environments can have either very
      similar or dissimilar parasite faunas. Additional tests showed that dissimilarity
      in flea or mite faunas between host geographic ranges was best explained by
      dissimilarity in vegetation, followed by dissimilarity in climatic conditions.
      Thus, external environmental factors may play greater roles than commonly thought
      in the evolution of host-parasite associations.

PMID- 20036669
TI  - Metarhizium anisopliae conidial responses to lipids from tick cuticle and tick
      mammalian host surface.
AB  - Conidial germination and the formation of appressoria are important events in the
      interactions between entomopathogenic fungi and their arthropod hosts. In this
      study, we demonstrate the effects of lipids extracted from tick epicuticle and
      the surface of a mammalian host (calf) on conidial germination and the
      development of appressoria in two subspecies of Metarhizium anisopliae, M.
      anisopliae var. anisopliae (M.an.an.-7) and M. anisopliae var. acridum (M.an.ac.
      5), which have different levels of virulence toward ticks. Pentane extracts of
      epicuticles of ticks susceptible and resistant to fungal infection always
      stimulated the germination of M.an.an.-7 conidia and the development of their
      appressoria; whereas the effects of dichloromethane (DCM) extracts of tick
      epicuticle varied depending on the tick. The DCM extracts from most of the tick
      species and developmental stages stimulated conidial germination and/or the
      formation of appressoria in M.an.an.-7. However, a DCM extract of lipids from the
      most resistant tick, engorged Hyalomma excavatum female, inhibited the
      germination of M.an.an.-7 conidia. Conidia of the non-virulent M.an.ac.-5 did not
      germinate on agarose amended with any of the examined tick extracts. However,
      when the tick extracts were placed on bactoagar, conidial germination increased 7
      to 8-fold. Extracts from the skin, hair and ear secretions of a calf stimulated
      conidial germination and the formation of appressoria in M.an.an.-7, but not
      M.an.ac.-5. This study demonstrates that lipids from tick epicuticles and
      mammalian skin selectively affect the germination of conidia of entomopathogenic
      fungi. The effects of these lipids may explain the variability in tick control
      these fungi provide for different hosts.

PMID- 20036670
TI  - Observation of a Bonamia sp. infecting the oyster Ostrea stentina in Tunisia, and
      a consideration of its phylogenetic affinities.
AB  - The small non-commercial oyster Ostrea stentina co-occurs with commercially
      important Ostrea edulis in the Mediterranean Sea, yet its disposition with
      respect to the destructive pathogens Bonamia ostreae and Marteilia refringens is
      unknown. We began an evaluation of the Bonamia spp. infection status of O.
      stentina from Hammamet, Tunisia, in June 2007 using polymerase chain reaction
      diagnostics followed by histology and in situ hybridization. Of 85 O. stentina
      sampled, nine were PCR-positive for a Bonamia sp. using a Bonamia genus-specific
      assay; of these nine, one displayed the uninucleate microcells associated with
      oyster hemocytes characteristic of Bonamia spp. There was no associated
      pathology. DNA sequencing of the parasite from this one infected individual
      revealed it to be of a member of the Bonamia exitiosa/Bonamia roughleyi clade, an
      identification supported by positive in situ hybridization results with probes
      specific for members of this clade, and by the morphology of the parasite cells:
      nuclei were central, as in B. exitiosa, not eccentric, as in B. ostreae. There is
      no basis for identifying the Tunisian parasite as either B. exitiosa or B.
      roughleyi, however, as these species are genetically indistinguishable. Likewise,
      there is no basis for identifying any of the other Bonamia spp. with affinities
      to the B. exitiosa/B. roughleyi clade, from Argentina, Australia, Spain, and the
      eastern USA, as one or the other of these named species. Though they are clearly
      distinct from Bonamia perspora and B. ostreae, justification for drawing species
      boundaries among the primarily austral microcells with affinities to B. exitiosa
      and B. roughleyi remains elusive.

PMID- 20036671
TI  - Inactivation and mechanisms of chlorine dioxide on Nosema bombycis.
AB  - Biological tests demonstrated that the inactivation of Nosema bombycis (N.
      bombycis) spores by chlorine dioxide (ClO(2)) occurs very fast and is highly
      sensitive. The lowest effective inactivation dosage and time was 15mg/mL for
      30min. The inactivation of spores was additionally verified by using double color
      fluorescence stain and spore germination testing. A series of biological changes,
      including a large number of substrates that were leaked out from the spores
      included proteins, DNA, polysaccharide, K(+), and Ca(2+), occurred a short time
      after N. bombycis spores were treated with ClO(2). In addition, the lipid of
      spores was disrupted and ATPase activity was inhibited, which resulted in the
      destruction of the inner structure of the spores.

PMID- 20036673
TI  - New discovery of Netrin-1 in cardioprotection.

PMID- 20036674
TI  - Post-weaning effects of milk and milk components on the intestinal mucosa in
      inflammation.
AB  - Many milk-derived components have immunomodulatory and anti-inflammatory
      properties, and some of these reduce intestinal inflammation when orally
      administered to animal models of colitis. However, the potential for ruminant
      milk or milk components to benefit people with intestinal inflammatory disorders
      (such as Inflammatory Bowel Disease) has not been well-researched. This review
      describes published research into mechanisms by which ruminant milk and its
      components may have beneficial effects when consumed by people who have
      intestinal inflammation.

PMID- 20036675
TI  - High frequency of somatic mutations in rat liver mitochondrial DNA.
AB  - Somatic mutations in mitochondrial DNA (mtDNA) are thought to play an important
      role in both aging and neurodegenerative diseases although their specific
      contributions remain a subject of intense debate. We analyzed somatic mutations
      in the mtDNA control regions in the liver of Wistar rats. The mutation rate was
      found to be high and increased with age from 5.3x10(-4) mutations per position to
      4.48x10(-3) mutations per position at 3 and 12 months of age, respectively. The
      vast majority of nucleotide substitutions are transitions ( approximately 95%)
      with A:T>G:C transitions being the most frequent type of substitution (>50%). In
      3-month-old Wistar rats, approximately 40% of somatic mutations in the control
      region of mtDNA are significantly consistent with the model of dislocation
      mutagenesis which is a signature of error-prone DNA synthesis by mtDNA polymerase
      gamma. The results are consistent with the previous hypothesis that normal
      intramitochondrial dNTP pool asymmetries, which have been shown to reduce the
      fidelity of mtDNA polymerase gamma, substantially contribute to somatic
      mutagenesis of the rat mtDNA.

PMID- 20036676
TI  - Peripheral antinociceptive effects of low doses of naloxone in an in vivo and in
      vitro model of trigeminal nociception.
AB  - Naloxone has been used to antagonize opioid effects for many years, even though
      at low doses it can exert antinociceptive effects. This 'paradoxical' analgesia
      has been detected after systemic administration of naloxone given alone or in
      combination with opioid drugs. In the present study, we investigated possible
      peripheral antinociceptive effects of low doses of naloxone using both an in vivo
      and in vitro model of trigeminal nociception. Low doses of naloxone injected
      locally into the rat wiskerpad elicited antinociceptive activity in the rat
      orofacial formalin test. The block of primary afferents with local administration
      of capsaicin suggested that naloxone acts both directly on sensory neurons and
      indirectly, by modulating the inflammatory component of the second phase of
      formalin test. Naloxone analgesia is maintained in rats made tolerant to the mu
      receptor agonist DAMGO, suggesting the involvement of delta- and kappa-opioid
      receptors. Subsequently, the effects of very low doses of naloxone were tested in
      primary cultures of rat trigeminal neurons activated with bradykinin, in order to
      elucidate the mechanisms of action underlying naloxone antinociceptive effects.
      Naloxone inhibited bradykinin-evoked CGRP release in two different experimental
      paradigms, i.e. primed and unprimed cultures, acting at the level of delta- and
      kappa-opioids receptors. These results suggest that low doses of naloxone can
      directly modulate the activation of the trigeminal neurons by modulating the
      activity of specific opioid receptors, and this effect may be clinically relevant
      in combined therapies where an increased analgesic effect is sought through the
      potentiation of peripheral mechanisms.

PMID- 20036677
TI  - Examining the sex difference in lateralisation for processing facial emotion:
      does biological sex or psychological gender identity matter?
AB  - The research examining sex differences in functional lateralisation has shown
      varying results. While some provide evidence for males being more strongly
      lateralised than females, a number have shown either no relationship or the
      opposite pattern of findings. In this study we consider whether psychological
      gender identity might clarify some of the conflicting results in this area of
      research. Eight five participants (39 males) aged from 18 to 49 years old were
      tested. We found that psychological masculinity was associated with stronger
      patterns of lateralisation for the processing of a range of emotional
      expressions. We also found an interaction between biological sex and
      psychological gender identity, with a positive relationship between psychological
      masculinity and lateralisation found for males, but a negative relationship found
      for females. The possible role of hormonal exposure in this relationship is
      discussed.

PMID- 20036678
TI  - Effect of disease severity and dopaminergic medication on recollection and
      familiarity in patients with idiopathic nondementing Parkinson's.
AB  - The effect of disease severity and dopaminergic medication on the assessment of
      familiarity and the recollection of episodic details during recognition in
      nondementing idiopathic Parkinson's is uncertain. Some studies have reported
      familiarity as deficient in mild Parkinson's yet others have found it intact even
      in moderate Parkinson's. Recollection has been found to be both preserved and
      deficient in mild and moderate Parkinson's. The extent to which these conflicting
      findings are explained by disease severity or dopaminergic medication or a
      combination of the two is uncertain, as all studies assessed patients in a
      medicated state, and disease severity has not always been consistently reported.
      Twelve patients with mild Parkinson's and 11 with moderate Parkinson's (medicated
      Hoehn and Yahr mean: 2.1 and 3.2, respectively), completed matched versions of a
      yes/no recognition memory test in a medicated and unmedicated condition (termed
      ON and OFF, respectively). Twenty-one matched healthy volunteers also completed
      both memory tasks in 2 separate sessions (termed Blue and Green, respectively).
      In the ON/Green condition, the moderate Parkinson's recollection performance was
      significantly poorer than the healthy volunteers and mild Parkinson's. By
      contrast, recognition memory and familiarity measures in both Parkinson's group
      were relatively spared. In the OFF/Blue condition, the moderate Parkinson's
      recollection was impaired, but only in relation to the healthy volunteer set.
      There were no significant differences in recollection performance between the
      mild and moderate Parkinson's groups. Again, recognition memory and familiarity
      measures in both Parkinson's group were relatively spared. Further analyses
      showed the moderate patients' recollection rates to be significantly poorer ON
      medication compared to OFF. These findings are discussed in relation to the
      staging of disease progression on medial temporal areas which separately support
      recollection and familiarity, and the putative effects the different classes of
      dopaminergic drugs may have on these areas.

PMID- 20036679
TI  - Accessibility of the nondominant language in picture naming: a counterintuitive
      effect of dementia on bilingual language production.
AB  - The current study tested the assumption that bilinguals with dementia regress to
      using primarily the dominant language. Spanish-English bilinguals with probable
      Alzheimer's disease (AD; n=29), and matched bilingual controls (n=42) named
      Boston Naming Test pictures in their dominant and nondominant languages.
      Surprisingly, differences between patients and controls were larger using
      dominant-language than nondominant-language naming scores, and bilinguals with AD
      were either more likely than controls (in English-dominant bilinguals), or
      equally likely (in Spanish-dominant bilinguals), to name some pictures in the
      nondominant language that they could not produce in their dominant language.
      These findings suggest that dominant language testing may provide the best
      assessment of language deficits in bilingual AD, and argue against the common
      notion that the nondominant language is particularly susceptible to dementia. The
      greater vulnerability of the dominant language may reflect the increased
      probability of AD affecting richer semantic representations associated with
      dominant compared to nondominant language names.

PMID- 20036681
TI  - Estimating genetic architectures from artificial-selection responses: a random
      effect framework.
AB  - Artificial-selection experiments on plants and animals generate large datasets
      reporting phenotypic changes in the course of time. The dynamics of the changes
      reflect the underlying genetic architecture, but only simple statistical tools
      have so far been available to analyze such time series. This manuscript describes
      a general statistical framework based on random-effect models aiming at
      estimating key parameters of genetic architectures from artificial-selection
      responses. We derive explicit Mendelian models (in which the genetic architecture
      relies on one or two large-effect loci), and compare them with classical
      polygenic models. With simulations, we show that the models are accurate and
      powerful enough to provide useful estimates from realistic experimental designs,
      and we demonstrate that model selection is effective in picking few-locus vs.
      polygenic genetic architectures even from medium-quality artificial-selection
      data. The method is illustrated by the analysis of a historical selection
      experiment, carried on color pattern in rats by Castle et al.

PMID- 20036680
TI  - Eye-blink rate predicts individual differences in pseudoneglect.
AB  - Most healthy individuals display a subtle spatial attentional bias, exhibiting
      relative inattention for stimuli on one side of the visual field, a phenomenon
      known as pseudoneglect. Prior work in animals and patients has implicated
      dopamine in spatial attention asymmetries. The current study therefore examined -
      in healthy individuals - the relationship between the attentional bias and
      spontaneous eye-blink rate (EBR), a putative measure of central dopaminergic
      function. We found that those individuals, who blinked more often under resting
      conditions, displayed greater preference for the right side of the visual display
      in a subsequent attention task. This finding may support the idea that the
      observed attentional bias in healthy individuals reflects asymmetries in
      dopaminergic circuits, and corroborates previous findings implicating dopamine in
      spatial attention.

PMID- 20036682
TI  - Isolation and characterization of two new Lys49 PLA2s with heparin neutralizing
      properties from Bothrops moojeni snake venom.
AB  - Among the proteins and peptides already characterized in Bothrops moojeni venom,
      two novel phospholipases A(2) (PLA(2)) have been purified and fully sequenced by
      ESI-MS/MS techniques. Both of them belong to the enzymatically non-active Lys49
      variants of PLA(2). They consist of 122 amino acids and share a characteristic
      sequence in their C-terminal region composed of clusters of basic amino acids
      known to interact with heparin. Thus, as already established, heparin can be used
      as an antidote to antagonize some myotoxic PLA(2)s from venoms of Bothrops genus.
      The two PLA(2) variants were shown to interact in vitro with unfractionated
      heparin (UFH) and low molecular weight heparin (LMWH), neutralizing their
      anticoagulant properties. Although the influences of PLA(2)s from snake venoms on
      the blood coagulation system are known, their use to antagonize the anticoagulant
      effect of heparin in vitro or in vivo has never been proposed. These finding
      recommend diagnostic and therapeutic applications, which are currently
      investigated.

PMID- 20036683
TI  - Mitochondrial dysfunction is associated with a pro-apoptotic cellular environment
      in senescent cardiac muscle.
AB  - Cardiac muscle undergoes significant remodeling with aging. This may be partly
      due to the progressive impairment of mitochondrial biogenesis and function. Our
      purpose was to examine how aging affects the subcellular localization of
      apoptogenic factors involved in mitochondrially mediated cell death in cardiac
      muscle. Employing 6- and 36-month-old Fischer 344xBN animals, we assessed markers
      of organelle content and function, as well as the mitochondrial and cytosolic
      compartmentalization of proteins implicated in apoptosis. Aging was associated
      with decrements in cardiac mitochondrial content and respiratory function. These
      changes were accompanied by a greater cytosolic accumulation of cytochrome c and
      AIF, as well as a higher mitochondrial Bax and a faster rate of permeability
      transition pore opening. Mitochondria from aged hearts demonstrated a greater
      enrichment of p66Shc and p46Shc providing further evidence of enhanced
      apoptogenic signaling. Opa1 was greater in the senescent myocardium, while Drp1
      was higher in the mitochondrial fraction of aged, compared to the young animals.
      Furthermore, the level of fragmented DNA was greater in the hearts of senescent
      animals. Thus, the specific compartmentalization of apoptogenic proteins implies
      that mitochondrially mediated cell death signaling is highly active in the aged
      myocardium, which may contribute to progressive cardiac pathophysiology.

PMID- 20036684
TI  - Crystal quality enhancement by magnetic fields.
AB  - From the latter half of the '90s, many studies of the effects of magnetic fields
      on protein crystallization have been carried out. It has been found that the
      crystallization of proteins under both homogeneous and inhomogeneous (gradient)
      magnetic fields enhances the quality of protein crystals. The quality enhancement
      is attributed to the magnetic orientation of protein crystals and the magnetic
      suppression of buoyancy convection in protein solutions. The magnetic fields also
      affect the kinetics of protein crystallization and hence change the habit of
      protein crystals. In this review, the effects of magnetic fields on protein
      crystallization, their mechanisms and indispensable future studies are outlined.

PMID- 20036685
TI  - Binding in voluntary action control.
AB  - The last decade has seen a proliferation of empirical studies that seek to
      understand how the cognitive system links voluntary motor actions with their
      perceptual effects. A view that has found considerable support in this research
      is the ideomotor approach to action control which holds that actors select,
      initiate, and execute a movement by activating anticipatory codes of the
      movement's sensory effects. We, first review the empirical evidence from
      different paradigms showing that effects of voluntary actions become anticipated
      during response production. In a second step we survey empirical data
      investigating the nature of the mechanisms that link voluntary motor actions with
      their intended and expected perceptual effects. We argue that the integration, or
      binding, of perceptual and motor codes occurs in action planning where features
      of intended effects are selectively bound to features of the actions that are
      selected to achieve these effects in the environment. As a final step we will
      summarize empirical findings that may elucidate the particular roles of effect
      code activation in response production and control.

PMID- 20036686
TI  - Organochlorine pesticides dieldrin and lindane induce cooperative toxicity in
      dopaminergic neurons: role of oxidative stress.
AB  - Elevated environmental exposure to pesticides has been implicated as a
      contributing factor in the pathogenesis of Parkinson's disease (PD), a
      progressive movement disorder resulted from degeneration of the nigrostriatal
      dopaminergic (DA) pathway. Organochlorine pesticides (OCPs) including dieldrin
      and lindane remain ubiquitous in the environment and food supply due to their
      resistance to degradation and bioaccumulation along the food chain. While prior
      studies have gained insight into the neurotoxic effects of individual OCPs such
      as dieldrin, the effect of combinations of coexisting OCPs is lacking. In this
      study, we determined the combined effect of dieldrin and lindane on DA neurons
      and potential mechanism of action. Combinations of dieldrin and lindane (5-25
      microM) were more effective in causing toxicity in immortalized rat N27 DA
      neurons than when used alone. Mechanistically, dieldrin and lindane combination
      induced a rapid increase in the levels of intracellular reactive oxygen species,
      a decrease in mitochondrial membrane potential and activation of caspase 3/7.
      Pretreatment with antioxidant N-acetyl cysteine blocked the effect of dieldrin
      and lindane on ROS generation and mitochondrial membrane potential and protected
      against dieldrin- and lindane-induced neurotoxicity. These results demonstrate
      that dieldrin and lindane work cooperatively to induce DA neurotoxicity through
      the induction of oxidative stress and mitochondrial dysfunction. These findings
      may advance understanding of the role of pesticides in the multi-factorial
      etiology of PD.

PMID- 20036687
TI  - Variations in the pharmacological profile of post-synaptic neurotoxins isolated
      from the venoms of the Papuan (Oxyuranus scutellatus canni) and coastal
      (Oxyuranus scutellatus scutellatus) taipans.
AB  - Based on murine LD(50) values, the taipans (i.e. Oxyuranus microlepidotus,
      Oxyuranus scutellatus and Oxyuranus scutellatus canni) are the most venomous
      snake genus in the world. Despite this, little is known about the toxins
      contained in their venoms. The aim of the present study was to isolate and
      characterise post-synaptic neurotoxins from the venoms of the Papuan taipan (O.
      s. canni) and coastal taipan (O. scutellatus), and to compare their pharmacology.
      A 6770Da toxin (i.e. alpha-oxytoxin 1) and a 6781Da toxin (i.e. alpha-scutoxin 1)
      were isolated from the venoms of O. s. canni and O. scutellatus, respectively,
      using reverse-phase high performance liquid chromatography. Both alpha-oxytoxin 1
      (0.3-1 microM) and alpha-scutoxin 1 (0.1-1 microM) caused concentration-dependent
      inhibition of indirect twitches in the chick biventer cervicis nerve-muscle
      preparation. Contractile responses to exogenous carbachol (CCh), but not
      potassium chloride (KCl), were inhibited by both toxins, suggesting a post
      synaptic mode of action. The inhibitory effect of alpha-oxytoxin 1 was reversed
      by washing. Cumulative concentration-response curves to CCh were obtained in the
      presence and absence of the toxins with the subsequently determined pA(2) of
      alpha-scutoxin 1 being 44.7-fold higher than alpha-oxytoxin 1 (i.e. 8.38+/-0.59
      versus 7.62+/-0.04). The current study shows that Papuan taipan and coastal
      taipan venom both contain potent post-synaptic neurotoxins which exhibit
      different pharmacological profiles. The effect of alpha-oxytoxin 1 is atypical of
      most snake venom post-synaptic neurotoxins displaying a 'competitive' mode of
      action, whereas alpha-scutoxin 1 possesses pseudo-irreversible or non-competitive
      activity.

PMID- 20036688
TI  - Circulating antibodies to endogenous erythropoietin and risk for HIV-1-related
      anemia.
AB  - OBJECTIVES: In a previous retrospective study we have shown that circulating
      antibodies to endogenous erythropoietin (anti-EPO) are associated with HIV-1
      related anemia. The present longitudinal cohort study was conducted to examine
      the effect of anti-EPO on the risk of developing anemia over time. METHODS: The
      study population consisted of 113 HIV-1 seropositive patients, who were screened
      for the presence of anti-EPO, with a mean+/-SD follow up of 105+/-40 months, for
      a total of 2190 visits. Anti-EPO were detected with an ELISA assay. RESULTS: Anti
      EPO were detected in 41% (46/113) at enrollment and 29% (320/1094) for all
      visits, and were associated with higher EPO levels for all visits (45.7+/-60.4
      vs. 31.8+/-31.7 IU/ml, p<0.001). After adjusting for other significant
      confounders, anti-EPO has been associated with increased risk of anemia both at
      enrollment (odds ratio [OR], 5.07; 95% confidence interval [CI], 1.25-20.49) as
      well as for all visits ([OR], 2.15; 95% [CI]: 1.29-3.56). During follow up, a
      decline in prevalence of both anti-EPO and anemia was observed as the percentage
      of patients receiving HAART was increasing. CONCLUSIONS: Anti-EPO are an
      independent risk factor for anemia in HIV-1-infected patients. HAART seems to
      reduce both anti-EPO and anemia prevalence.

PMID- 20036689
TI  - Predictors and outcomes of respiratory failure among hospitalized pneumonia
      patients with 2009 H1N1 influenza in Taiwan.
AB  - OBJECTIVES: The worldwide outbreak of a pandemic influenza A (H1N1) virus began
      in April 2009. We characterized the clinical features of the hospitalized
      pneumonia patients with 2009 H1N1 influenza in Taiwan and elucidated the risk of
      those patients for developing respiratory failure. METHODS: Severe complicated
      influenza infection is a notifiable disease in Taiwan and the hospitalized
      pneumonia patients with 2009 H1N1 influenza were reported accordingly. We
      reviewed the medical records of the eligible cases by September 8, 2009;
      development of respiratory failure was the primary endpoint. RESULTS: Of the 96
      patients we studied, 22 (23%) developed respiratory failure. Among those, 10
      (45%) died and all of the non-respiratory failure patients survived. Age
      distribution, presence of dyspnea, lymphopenia, leukopenia, PaO(2)/FiO(2) ratio,
      PaCO(2), SOFA score, infiltration on chest x-ray at admission were different
      between two groups by univariate analysis. The clinical course was also
      different, with longer duration from onset of symptoms to use of oseltamivir,
      longer hospital stay, and more complications during hospitalization in patients
      with respiratory failure. A multivariate logistic regression showed an
      association between development of respiratory failure and SOFA score > or = 4 at
      admission, initial lymphocyte count < or = 800/microL, and the duration from
      symptom onset to initiation of oseltamivir > 48 h. CONCLUSIONS: Respiratory
      failure in patients with 2009 H1N1 influenza leads to poor outcomes, including
      complications and death. Clinicians could apply the three predictors at admission
      to identify the high-risk pneumonic patients for developing respiratory failure.
      Further study is needed to validate the findings of this study in other settings.

PMID- 20036690
TI  - A miniaturized chronic microelectrode drive for awake behaving head restrained
      mice and rats.
AB  - The present work introduces an electrode microdrive system small enough to be
      placed into two distinct brain areas in head-fixed mice. To meet the space
      constraint imposed by the size of mice and the additional presence of a head
      post, the size and weight of the components were minimized. In the current
      version, an individual microdrive moves an array of four Reitboeck type
      electrodes. We report about successful implantation in rats and mice using one or
      two microdrives. Using two of these devices in individual mice/rats, the
      recording of parallel single and multi-unit as well as local field potential from
      prefrontal, motor, somatosensory cortex and hippocampus is demonstrated. The
      system can be easily constructed with machinery and equipment present in most
      neurophysiology labs.

PMID- 20036691
TI  - Semi-automatic stereotactic coordinate identification algorithm for routine
      localization of Deep Brain Stimulation electrodes.
AB  - Deep Brain Stimulation (DBS) is a routine therapy for movement disorders, and has
      several emerging indications. We present a novel protocol to define the
      stereotactic coordinates of metallic DBS implants that may be routinely employed
      for validating therapeutic anatomical targets. Patients were referred for
      troubleshooting or new DBS implantation. A volumetric MRI of the brain obtained
      prior to or during this protocol was formatted to the Anterior Commissure
      Posterior Commissure (AC-PC) coordinate system. Patients underwent a CT scan of
      the brain in an extended Hounsfield unit (EHU) mode. A semi-automatic detection
      algorithm based on a Normalized Mutual Information (NMI) co-registration method
      was implemented to measure the AC-PC coordinates of each DBS contact. This
      algorithm was validated using manual DBS contact identification. Fifty MRI-CT
      image pairs were available in 39 patients with a total of 336 DBS electrodes. The
      median and mean Euclidean distance errors for automatic identification of
      electrode locations were 0.20mm and 0.22 mm, respectively. This method is an
      accurate method of localization of active DBS contacts within the sub-cortical
      region. As the investigational indications of DBS expand, this method may be used
      for verification of final implant coordinates, critical for understanding
      clinical benefit and comparing efficacy between subjects.

PMID- 20036692
TI  - Selection of reference genes for gene expression studies in rat oligodendrocytes
      using quantitative real time PCR.
AB  - Quantitative real time polymerase chain reaction (qPCR) has become a widely used
      tool to examine gene expression levels. Reliable quantification, however, depends
      on a proper normalization strategy. Normalization with multiple reference genes
      is becoming the standard, although the most suitable reference genes depend on
      the applied treatment as well as the tissue or cell type studied. In this study
      the stability of various reference genes was investigated in cultures of
      oligodendrocytes derived from either mature or neonatal rats, the latter also in
      the presence of the liver X receptor (LXR) agonist. The expression stability of
      ten commonly used reference genes (HPRT, GAPDH, 18S, ActB, CycA, Tbp, Rpl13A,
      YWHAZ, HMBS, Pgk1) was analyzed using geNorm and NormFinder. When comparing the
      different types of cell cultures, Rpl13A, CycA, Pgk1 and YWHAZ were identified as
      most stable genes. After LXR agonist treatment, CycA, Pgk1 and Rpl13A were found
      to be the most stable by both geNorm and NormFinder. HMBS and the commonly used
      housekeeping genes GAPDH and 18S turned out to be the most variable according to
      geNorm and NormFinder. In conclusion, the use of multiple reference genes,
      instead of only one, in qPCR experiments with rat oligodendrocytes is strongly
      advised and standard housekeeping genes such as GAPDH and 18S are not recommended
      as they appear to be relatively unstable under the experimental conditions used.
      Reference gene selection should always be performed for each individual
      experiment, since useful reference genes are very specific for every situation.

PMID- 20036693
TI  - The threshold of amylin-induced anorexia is lower in chicks selected for low
      compared to high juvenile body weight.
AB  - Chicks that have undergone long-term selection for low body weight responded to
      intracerebroventricular amylin injection with reduced food intake at a dose
      considerably lower and with a greater magnitude suppression than those selected
      for high body weight. Behaviors unrelated to ingestion were not affected. These
      data support the thesis of correlated amylin system responses to selection for
      low or high body weight, with possible implications to other species.

PMID- 20036694
TI  - The temporal attributes of episodic memory.
AB  - From a temporal dynamic processing point of view, episodic memory can be divided
      into three critical time periods: short-term episodic memory with a duration of
      seconds, intermediate-term episodic memory with a duration from minutes to hours,
      and long-term or remote episodic memory with a duration from days to years. We
      propose that short-term episodic memory is mediated by the CA3 subregion of the
      hippocampus, intermediate-term episodic memory is mediated by the CA1 subregion
      of the hippocampus (in certain situations aided by the CA3 subregion), and that
      long-term or remote episodic memory may be mediated by the CA1 subregion. In
      support of the above mentioned proposal data are presented to support the short
      term and intermediate episodic memory functions of CA3 and CA1 based on single
      item object, spatial location, and object-place association tasks. Additional
      data are presented for a role for CA3 in short-term episodic memory based on
      multiple sequential spatial locations, visual objects, and odors tasks. The same
      episodic memory model based on duration mentioned above cannot easily be applied
      to the functions of the CA3 (short-term episodic) and CA1 (intermediate-term
      episodic) for a multiple sequentially presented item, such as a places, objects
      or odors. The reason for this is that the CA1 region supports, in addition to
      intermediate episodic memory, temporal pattern separation processes which would
      reduce interference among sequentially experienced items. The consequence is that
      this temporal pattern separation process can result in CA1 involvement in short
      term episodic tasks based on duration. Also, data are presented based on tasks
      that involved multiple-trials tested within a day and between days short-term and
      intermediate-term episodic memory. Furthermore, the mechanisms for understanding
      the interactions and dissociations between CA3 and CA1 are discussed. The DG
      appears to have a modulatory influence on the CA3 and CA1 mediation of short-term
      and intermediate-term episodic memory. The role of CA1 in supporting remote
      episodic memory requires more experimentation.

PMID- 20036695
TI  - Anabolic steroids have long-lasting effects on male social behaviors.
AB  - Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing.
      Adolescence involves remodeling of steroid-sensitive neural circuits that mediate
      social behaviors, and previous studies using animal models document effects of
      AAS on male social behaviors. The present experiments tested whether AAS have
      persistent and more pronounced behavioral consequences when drug exposure occurs
      during adolescence as compared to exposure in adulthood. Male Syrian hamsters
      were injected daily for 14 days with either vehicle or an AAS cocktail containing
      testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone
      undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or
      adulthood (63-77 days of age). As adults, subjects were tested two or four weeks
      after the last injection for either sexual behavior with a receptive female or
      male-male agonistic behavior in a resident-intruder test. Compared with vehicle
      treated males, AAS-treated males, regardless of age of treatment, displayed fewer
      long intromissions and a significant increase in latency to the first long
      intromission, indicative of reduced potential to reach sexual satiety. Increased
      aggression was observed in males exposed to AAS compared with males treated with
      vehicle, independently of age of AAS treatment. However, unlike hamsters exposed
      to AAS in adulthood, hamsters exposed to AAS during adolescence did not display
      any submissive or risk-assessment behaviors up to 4 weeks after discontinuation
      of AAS treatment. Thus, AAS have long-lasting effects on male sexual and
      agonistic behaviors, with AAS exposure during adolescence resulting in a more
      pronounced reduction in submissive behavior compared to AAS exposure in
      adulthood.

PMID- 20036697
TI  - An implantable, focal brain cooling device suppresses nociceptive pain in rats.
AB  - Although the classic idea of controlling pain through focal brain cooling is
      intriguing, the mechanism of this effect still remains to be elucidated. A
      thermoelectronic cooling system was developed and chronically implanted on the
      ipsilateral sensorimotor cortex of rats. Significant suppression of nociceptive
      pain was observed in limbs contralateral to the cooling cortex in hot plate tests
      and thermal withdrawal tests (p<0.05), with a minimal influence on neurological
      functions. This study identified, for the first time, the specific site and
      temperatures for the suppression of nociceptive pain, thus showing the potential
      feasibility of thermal neuromodulation therapy for pain.

PMID- 20036698
TI  - Aggregation and cytotoxic properties towards cultured cerebrovascular cells of
      Dutch-mutated Abeta40 (DAbeta(1-40)) are modulated by sulfate moieties of
      heparin.
AB  - Glycosaminoglycans (GAGs), in particular as part of heparan sulfate
      proteoglycans, are associated with cerebral amyloid angiopathy (CAA). Similarly,
      GAGs are also associated with the severe CAA found in patients suffering from
      hereditary cerebral hemorrhage with amyloidosis of the Dutch type (HCHWA-D),
      where the amyloid beta (Abeta) peptide contains the Dutch mutation (DAbeta(1
      40)). This suggests a role for GAGs in vascular Abeta aggregation. It was the aim
      of this study to investigate the effect of different GAGs (heparin, chondroitin
      sulfate, heparan sulfate), the macromolecule dextran sulfate and, using
      desulfated heparins, the role of GAG sulfate moieties on the in vitro aggregation
      of CAA-associated DAbeta(1-40) and on DAbeta(1-40)-induced toxicity of cultured
      cerebrovascular cells. We also aimed to study the in vivo distribution of various
      sulfated heparan sulfate GAG epitopes in CAA. Of all GAGs tested, heparin was the
      strongest inducer of aggregation of DAbeta(1-40) in the different aggregation
      assays, with both heparin and heparan sulfate reducing Abeta-induced cellular
      toxicity. Furthermore, (partial) removal of the sulfate moieties of heparin
      partially abolished the effects of heparin on aggregation and cellular toxicity,
      suggesting an essential role for the sulfate moieties in heparin. Finally, we
      demonstrated the in vivo association of sulfated heparan sulfate (HS) GAGs with
      CAA. We conclude that sulfate moieties within GAGs, like heparin and HS, have an
      important role in Abeta aggregation in CAA and in Abeta-mediated toxicity of
      cerebrovascular cells.

PMID- 20036696
TI  - Redox signaling via lipid raft clustering in homocysteine-induced injury of
      podocytes.
AB  - Our recent studies have indicated that hyperhomocysteinemia (hHcys) may induce
      podocyte damage, resulting in glomerulosclerosis. However, the molecular
      mechanisms mediating hHcys-induced podocyte injury are still poorly understood.
      In the present study, we first demonstrated that an intact NADPH oxidase system
      is present in podocytes as shown by detection of its membrane subunit
      (gp91(phox)) and cytosolic subunit (p47(phox)). Then, confocal microscopy showed
      that gp91(phox) and p47(phox) could be aggregated in lipid raft (LR) clusters in
      podocytes treated with homocysteine (Hcys), which were illustrated by their
      colocalization with cholera toxin B, a common LR marker. Different mechanistic LR
      disruptors, either methyl-beta-cyclodextrin (MCD) or filipin abolished such Hcys
      induced formation of LR-gp91(phox) or LR-p47(phox) transmembrane signaling
      complexes. By flotation of detergent-resistant membrane fractions we found that
      gp91(phox) and p47(phox) were enriched in LR fractions upon Hcys stimulation, and
      such enrichment of NADPH oxidase subunits and increase in its enzyme activity
      were blocked by MCD or filipin. Functionally, disruption of LR clustering
      significantly attenuated Hcys-induced podocyte injury, as shown by their
      inhibitory effects on Hcys-decreased expression of slit diaphragm molecules such
      as nephrin and podocin. Similarly, Hcys-increased expression of desmin was also
      reduced by disruption of LR clustering. In addition, inhibition of such LR
      associated redox signaling prevented cytoskeleton disarrangement and apoptosis
      induced by Hcys. It is concluded that NADPH oxidase subunits aggregation and
      consequent activation of this enzyme through LR clustering is an important
      molecular mechanism triggering oxidative injury of podocytes induced by Hcys.

PMID- 20036699
TI  - Composition vector approach to whole-genome-based prokaryotic phylogeny: success
      and foundations.
AB  - Composition vector approach to prokaryotic phylogeny provides an alignment-free
      and parameter-free method based on whole-genome data. It has also been applied to
      viruses and fungi. In all studied cases the inferred phylogenetic relationships
      agree well with taxonomic knowledge in major groupings and fine branchings. In
      this review article, after demonstrating its successful application to a
      collection of 892 genomes including 62 Archaea, 822 Bacteria and 8 Eukarya, we
      will outline some ongoing work towards the foundations of this new approach.

PMID- 20036700
TI  - Continuous production of lactulose by immobilized thermostable beta-glycosidase
      from Pyrococcus furiosus.
AB  - A continuous enzymatic process for the production of the prebiotic disaccharide
      lactulose through transgalactosylation was developed using free and immobilized
      beta-glycosidase from Pyrococcus furiosus. The hyperthermostable beta-glycosidase
      (CelB) was immobilized onto an anion-exchange resin (Amberlite IRA-93) or onto
      Eupergit C with immobilization yields of 72% and 83%, respectively. The
      immobilized biocatalysts demonstrated specific activities of 920 nkat g(-1) dry
      carrier and 1500 nkat g(-1) dry carrier at 75 degrees C with p-nitrophenyl-beta-D
      galactopyranoside as substrate. Continuous biotransformations in packed-bed
      reactors using carrier bound CelB and in an enzyme membrane reactor using free
      CelB were carried out at 75 degrees C. Maximum lactulose yields of 43% related to
      the initial lactose concentration were reached with the carrier bound CelB
      preparations. The corresponding productivities were 52 glactulose l(-1)h(-1)
      (Amberlite IRA-93) and 15 glactulose l(-1)h(-1) (Eupergit C), respectively. The
      free enzyme tested in an enzyme membrane reactor showed a product yield of 41%
      and a productivity of 12 glactulose l(-1)h(-1) in the first day. While both
      carrier bound CelB preparations were 100% stable for at least 14 days, the half
      life of the free CelB in the enzyme membrane reactor was only about 1.5 days.

PMID- 20036701
TI  - Systems-level modeling--a new approach for engineering efficient photosynthetic
      machinery.
AB  - Photosynthesis produces the basic building block for crop biomass and yields;
      however, improving photosynthesis has not been effectively used as a breeding
      goal. More and more evidences suggested that improving photosynthesis can
      substantially increase crop yields. The complexity of photosynthesis however
      makes experimentally identifying new ways to engineer higher photosynthesis
      inherently time-consuming and costly. Combining systems modeling with
      evolutionary algorithm makes it possible to identify optimal engineering options
      for future global climate change scenarios and simultaneously consider
      environmental constraints, such as with constant or even decreasing nitrogen
      fertilizer application in the field. This method enables in silico examination of
      a large number of engineering options which natural selection has not explored,
      for higher photosynthetic energy conversion efficiency. The new approach comes
      particularly timely for now when our society is facing serious challenges in food
      security and global climate change. The traditional reductionist's approach will
      continue generating critical knowledge required to support this systems biology
      method to engineering higher photosynthesis.

PMID- 20036702
TI  - Linkage of hippocampal proteins to spatial memory formation and strain-dependence
      in Apodemus sylvaticus, C57BL/6J and PWD/PhJ mice.
AB  - Strain-dependence of performance in the Morris water maze (MWM) has been reported
      but information on underlying differences at the protein level as well as linkage
      of hippocampal proteins to memory is limited. No data are available on
      differences in hippocampal protein levels between (within-strain) "good" and
      "bad" performers in the MWM. Hippocampi of wild-caught mouse strain Apodemus
      sylvaticus (AS), laboratory inbred mouse strain C57BL/6J and wild-derived inbred
      mouse strain PWD/PhJ, that were tested in the MWM, were taken and postsynaptic
      density protein 95, neuronal marker protein NeuN, dendritic spine protein
      drebrin, synapsins 1a and 1b and synaptosomal protein syntaxin of the SNARE
      complex were determined by immunoblotting. These mouse strains with known
      different performance in the MWM showed different hippocampal protein patterns
      and by the use of yoked controls proteins could be identified as linked to memory
      formation. When mice, classified as good or bad performers by the median of time
      spent in the target quadrant on day 12 of the MWM, experiments, NeuN was
      discriminating good from bad performers in AS at the stringent statistical level
      of P<0.0001, an effect not seen in the corresponding yoked controls. Strain
      dependence of performance in the MWM was reflected by different hippocampal
      protein levels. Most hippocampal proteins given above were linked to memory
      formation in the MWM. The finding that the neuronal protein NeuN is able to
      discriminate between good and bad performers in the MWM may be of major interest
      and may open a new area in the search for protein markers of spatial memory
      performance.

PMID- 20036703
TI  - Excitatory amino acids and monoaminergic neurotransmitters in cerebrospinal fluid
      of acute ischemic stroke patients.
AB  - BACKGROUND AND PURPOSE: Improved insight in the role of neurotransmitters in
      acute cerebral ischemic injury may be fundamental for the successful development
      of novel therapeutic approaches. We investigated excitatory amino acids and
      monoaminergic neurotransmitters in cerebrospinal fluid (CSF) of acute ischemic
      stroke patients and their relation to stroke characteristics. METHODS: CSF
      concentrations of glutamate, aspartate, glutamine, glycine, proline, taurine,
      norepinephrine, 5-hydroxyindoleacetic acid, homovanillic acid and 3,4
      dihydroxyphenylacetic acid were assessed in 89 stroke patients at admission
      (median 6.3h after stroke onset) and in 31 controls. We evaluated the relation
      between CSF concentrations and (a) stroke severity (NIHSS score at admission,
      lesion volume), (b) stroke evolution in the subacute phase, (c) long-term stroke
      outcome, (d) lesion location, and (e) stroke etiology. RESULTS: Neurotransmitter
      systems display relevant interrelations, however, no significant associations
      between neurotransmitter concentrations in CSF and stroke characteristics were
      found, with the exception of higher 5-hydroxyindoleacetic acid levels in CSF of
      patients with progressing stroke and poor long-term outcome. CONCLUSIONS: The
      study results question the added value of neurotransmitter assessment in CSF for
      research on ischemic cerebral injury.

PMID- 20036705
TI  - Study of killer immunoglobulin-like receptor genes and human leukocyte antigens
      class I ligands in a Caucasian Brazilian population with Crohn's disease and
      ulcerative colitis.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory
      diseases of the bowel, of unknown origin. Exposure to specific environmental
      factors by genetically susceptible individuals, leading to an inadequate response
      of the immune system, is one of the potential explanations for the occurrence of
      these diseases. Natural killer cells are part of the innate immune system
      recognizing class I HLA (human leukocyte antigen) molecules on target cells
      through their membrane receptors. The main receptors of the natural killer cells
      are the killer immunoglobulinlike receptors (KIRs). Our study aimed to evaluate
      the association between the KIR genes in patients with inflammatory bowel
      diseases and healthy controls. We typed 15 KIR genes and HLA class I ligands in
      248 unrelated Brazilian Caucasians, of which 111 had UC and 137 had CD, and 250
      healthy controls by polymerase chain reaction using sequence-specific
      oligonucleotides and sequence-specific primers. We found an increase in KIR2DL2
      in controls (inflammatory bowel disease [IBD]: p < 0.001; UC: p = 0.01; CD: p =
      not significant [NS]). The genotype 2DL2+/HLA-C lys(80)+ was also more common in
      controls (IBD: p = 0.005; UC: p = 0.01; CD: p = NS); as well as 2DL1+/HLA-C
      Asn(80)+ (IBD: p = 0.026; UC: p = NS;CD: p = NS). The imbalance between
      activating and inhibitory KIR and HLA ligands may explain, at least in part, the
      pathogenesis of these inflammatory bowel diseases.

PMID- 20036704
TI  - Use of NAD(P)H and flavoprotein autofluorescence transients to probe neuron and
      astrocyte responses to synaptic activation.
AB  - Synaptic stimulation in brain slices is accompanied by changes in tissue
      autofluorescence, which are a consequence of changes in tissue metabolism.
      Autofluorescence excited by ultraviolet light has been most extensively studied,
      and is due to reduced pyridine nucleotides (NADH and NADPH, collectively termed
      NAD(P)H). Stimulation generates a characteristic compound NAD(P)H response,
      comprising an initial fluorescence decrease and then an overshooting increase
      that slowly recovers to baseline levels. Evoked NAD(P)H transients are relatively
      easy to record, do not require the addition of exogenous indicators and have good
      signal-noise ratios. These characteristics make NAD(P)H imaging methods very
      useful for tracking the spread of neuronal activity in complex brain tissues,
      however the cellular basis of synaptically-evoked autofluorescence transients has
      been the subject of recent debate. Of particular importance is the question of
      whether signals are due primarily to changes in neuronal mitochondrial function,
      and/or whether astrocyte metabolism triggered by glutamate uptake may be a
      significant contributor to the overshooting NAD(P)H fluorescence increases. This
      mini-review addresses the subcellular origins of NAD(P)H autofluorescence and the
      evidence for mitochondrial and glycolytic contributions to compound transients.
      It is concluded that there is no direct evidence for a contribution to NAD(P)H
      signals from glycolysis in astrocytes following synaptic glutamate uptake. In
      contrast, multiple lines of evidence, including from complimentary flavoprotein
      autofluorescence signals, imply that mitochondrial NADH dynamics in neurons
      dominate compound evoked NAD(P)H transients. These signals are thus appropriate
      for studies of mitochondrial function and dysfunction in brain slices, in
      addition to providing robust maps of postsynaptic neuronal activation following
      physiological activation.

PMID- 20036706
TI  - An unusual liver mass.

PMID- 20036707
TI  - Investigation of antioxidant, anti-inflammatory and DNA-protective properties of
      eugenol in thioacetamide-induced liver injury in rats.
AB  - The present study investigated the preventive effect of eugenol, a naturally
      occurring food flavouring agent on thioacetamide (TA)-induced hepatic injury in
      rats. Adult male Wistar rats of body weight 150-180 g were used for the study.
      Eugenol (10.7 mg/kg b.w./day) was administered to rats by oral intubation for 15
      days. TA was administered (300 mg/kg b.w., i.p.) for the last 2 days at 24h
      interval and the rats were sacrificed on the 16th day. Markers of liver injury
      (aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma
      glutamyl transferase and bilirubin), inflammation (myeloperoxidase, tumor
      necrosis factor-alpha and interleukin-6), oxidative stress (lipid peroxidation
      indices, protein carbonyl and antioxidant status) and cytochrome P4502E1 activity
      were assessed. Expression of cyclooxygenase-2 (COX-2) and the extent of DNA
      damage were analyzed using immunoblotting and comet assay, respectively. Liver
      injury and collagen accumulation were assessed using histological studies by
      hematoxylin and eosin and Masson trichrome staining. Rats exposed to TA alone
      showed increased activities of hepatocellular enzymes in plasma, lipid
      peroxidation indices, inflammatory markers and pro-inflammatory cytokines and
      decreased antioxidant status in circulation and liver. Hepatic injury and
      necrosis were also evidenced by histology. Eugenol pretreatment prevented liver
      injury by decreasing CYP2E1 activity, lipid peroxidation indices, protein
      oxidation and inflammatory markers and by improving the antioxidant status.
      Single-cell gel electrophoresis revealed that eugenol pretreatment prevented DNA
      strand break induced by TA. Increased expression of COX-2 gene induced by TA was
      also abolished by eugenol. These findings suggest that eugenol curtails the toxic
      effects of TA in liver.

PMID- 20036708
TI  - The Mullerian HOXA10 gene promotes growth of ovarian surface epithelial cells by
      stimulating epithelial-stromal interactions.
AB  - The ovarian surface epithelium (OSE) origin of ovarian cancers has been
      controversial because these cancers often exhibit Mullerian-like features. One
      hypothesis is that ovarian neoplasia involves the gain of growth advantages by
      OSE cells via activation of Mullerian programs. The homeobox gene HOXA10 controls
      formation of the uterus from the Mullerian ducts, and is not expressed in normal
      OSE. We previously found that HOXA10 is expressed in ovarian cancers with
      endometrial-like features, and induces transformed OSE cells to form glandular
      tumors in mice. In the current study, we found that induction of HOXA10 in OSE
      cells promotes homophilic cell adhesion and prevents anoikis. HOXA10 expression
      stimulated interactions of OSE cells with the extracellular matrix proteins
      vitronectin and fibronectin, and with mesothelial cells of the omentum which is a
      common attachment site for ovarian cancer cells. HOXA10 also stimulated
      interactions of OSE cells with omental fibroblasts, and these interactions
      promoted OSE cell growth. Our findings indicate that aberrant activation of a
      Mullerian program in OSE cells confers growth advantages by stimulating cellular
      interactions with the microenvironment.

PMID- 20036709
TI  - Ghrelin stimulation of gonadotropin (LH) release from goldfish pituitary cells:
      presence of the growth hormone secretagogue receptor (GHS-R1a) and involvement of
      voltage-sensitive Ca2+ channels.
AB  - Ghrelin (GRLN) stimulates maturational gonadotropin (LH) secretion in goldfish.
      This study identified GRLN receptors (GHS-Rs) in goldfish tissues and examined
      the involvement of voltage-sensitive Ca(2+) channels (VSCCs) in ghrelin action. A
      partial goldfish GHS-R1a sequence was obtained and expression observed in brain,
      pituitary, spleen, kidney, heart, gill, ovary, testis, and intestine. Synthetic
      goldfish GRLN (gGRLN(19)) stimulated LH secretion from dispersed goldfish
      pituitary cells in column perifusion and increased intracellular Ca(2+)
      ([Ca(2+)](i)) in identified goldfish gonadotropes. gGRLN(19) did not stimulate LH
      secretion either in the presence of Ca(2+)-free media, or the L-type VSCC
      inhibitors nifedipine and verapamil. Similarly, gGRLN(19)-elicited increases in
      [Ca(2+)](i) were attenuated by Ca(2+)-free media and nifedipine. Furthermore,
      when LH release and [Ca(2+)](i) were elevated by Bay K8644, gGRLN(19) had no
      further effect. These results indicate that GHS-R1a is present in goldfish
      pituitary and Ca(2+) entry through VSCC mediates direct gGRLN(19) action on LH
      release in goldfish pituitary cells.

PMID- 20036710
TI  - Berberine modulates insulin signaling transduction in insulin-resistant cells.
AB  - Berberine has been shown to have insulin-sensitizing effect, but the molecular
      mechanism underlying remains elusive. In this work, we investigated the effect of
      berberine on insulin-induced signal transduction and glucose uptake in both
      insulin-sensitive and insulin-resistant rat skeletal muscle cells. Berberine
      increased the activity of AMPK and PKCzeta and AS160 phosphorylation in normal
      cells, but had little effect on PKB activation. In insulin-resistant state,
      berberine exhibited synergistic effect on insulin-induced glucose uptake and
      GLUT4 translocation. Berberine improved insulin-induced tyrosine-phosphorylation
      of IRS-1 and the recruitment of p85 to IRS-1. These changes were accompanied by
      enhancement in insulin-induced PKCzeta and PKB activity and actin remodeling. The
      ameliorated insulin signal transduction was related to the inhibition of mTOR by
      berberine, which attenuated serine-phosphorylation of IRS-1. These results
      suggest that berberine may overcome insulin resistance via modulating key
      molecules in insulin signaling pathway, leading to increased glucose uptake in
      insulin-resistant cells.

PMID- 20036711
TI  - Inhibition of goiter growth and of cyclic AMP formation in rat thyroid by 2
      iodohexadecanal.
AB  - INTRODUCTION: Thyroid autoregulation has been related to intraglandular content
      of an unknown putative iodocompound. The thyroid is capable of producing
      different iodolipids such as 6-iodo-deltalactone (ILdelta) and 2-iodohexadecanal
      (2-IHDA). Data from different laboratories have shown that these iodolipids
      inhibit several thyroid parameters. ILdelta has an antigoitrogenic action but no
      data about the action of 2-IHDA on this parameter has been published. OBJECTIVES:
      to study the action of 2-IHDA on methimazole (MMI)-induced goiter and analyze if
      this compound can cause the involution of preformed goiter. RESULTS:
      Administration of MMI to rats during 10 days increased thyroid weight by 112%.
      This effect was significantly inhibited by the simultaneous injection of
      20mug/day of 2-IHDA (51% vs. MMI) while iodine or non iodinated hexadecanal were
      without action. Thyroidal proliferating cell nuclear antigen (PCNA) content was
      increased by MMI while 2-IHDA decreased this value (control: 100%; MMI: 190+/-11;
      MMI+2-IHDA: 134+/-10). Serum TSH was increased after MMI administration and 2
      IHDA did not modify this parameter (control: 1.89+/-0.10; MMI: 8.19+/-0.93ng/ml;
      MMI+2-IHDA: 7.38+/-0.72). Treatment with MMI increased thyroidal cAMP content
      (control: 16.1+/-0.82, MMI: 42.4+/-4.6 fmol/mg protein) while injection of 2-IHDA
      significantly decreased this value (22.3+/-2.0). Goiter prevention by 2-IHDA was
      also observed at 30 days of treatment reducing total number of cells (51%
      inhibition) and epithelial height (81% inhibition). Goiter involution was induced
      after withdrawal of MMI and injection with 2-IHDA, KI or saline. 2-IHDA led to a
      reduction of 74.5% in thyroid weight after 3 days while spontaneous involution
      (saline) was only of 32%. KI failed to alter this value. This significant
      involution was accompanied by a reduction in the number of cells (66%).
      Administration of the iodolipids did not produce significant changes in several
      serum parameters such as total T(3) and T(4), cholesterol, transaminases, urea
      and creatinine. CONCLUSION: 2-Iodohexadecanal, as 6-iodo-deltalactone, prevents
      goiter growth in rats and opens a potential therapeutic application of
      iodolipids.

PMID- 20036712
TI  - Increased blood vessel density and endothelial cell proliferation in multiple
      sclerosis cerebral white matter.
AB  - Multiple sclerosis (MS) is primarily considered an inflammatory demyelinating
      disease, however the role of vasculature in MS pathogenesis is now receiving much
      interest. MS lesions often develop along blood vessels and alterations in blood
      brain barrier structure and function, with associated changes in the basement
      membrane, are pathological features. Nevertheless, the possibility of
      angiogenesis occurring in MS has received little attention. In this study we used
      triple label enzyme immunohistochemistry to investigate blood vessel density and
      endothelial cell proliferation in MS samples (n=39) compared with control tissue
      to explore evidence of angiogenesis in MS. The results showed that in all MS
      samples examined blood vessel density increased compared with controls. The
      greatest increase was found in subacute lesions where numbers of positively
      stained vessels increased from 43.9+/-8.5% in controls to 84.2+/-13.3% (P=0.001).
      Furthermore, using an antibody against endoglin (CD105), a specific marker of
      proliferating endothelial cells, which are characteristic of angiogenesis, we
      have shown that vessels containing proliferating endothelial cells were more
      pronounced in all MS tissue examined (normal-appearing white matter, acute,
      subacute and chronic lesions, P>or=0.027) compared with control and this was
      greatest in the MS normal-appearing white matter (68.8+/-19.8% versus 10.58+/
      6.4%, P=0.003). These findings suggest that angiogenesis may play a role in
      lesion progression, failure of repair and scar formation.

PMID- 20036713
TI  - Behavior and serotonergic disorders in rats exposed prenatally to valproate: a
      model for autism.
AB  - In order to explore whether some aspects of the autistic phenotype could be
      related to impairment of the serotonergic system, we chose an animal model which
      mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the
      9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats
      at E9 caused a dramatic shift in the distribution of serotonergic neurons on
      postnatal day 50 (PND50). Behavioral studies have also been performed but on rats
      that were exposed to VPA later (E12.5). Our aim was to test whether VPA exposure
      at E9 induces comparable behavioral impairments than at E12.5 and causes
      serotonergic impairments which could be related to behavioral modifications. The
      results showed significant behavioral impairments such as a lower tendency to
      initiate social interactions and hyperlocomotor activity in juvenile male rats.
      The serotonin levels of these animals at PND50 were decreased (-46%) in the
      hippocampus, a structure involved in social behavior. This study suggests that
      VPA could have a direct or indirect action on the serotonergic system as early as
      the progenitor cell stage. Early embryonic exposure to VPA in rats provides a
      good model for several specific aspects of autism and should help to continue to
      explore pathophysiological hypotheses.

PMID- 20036714
TI  - The selective serotonin reuptake inhibitor fluoxetine reduces striatal in vivo
      levels of voltammetric nitric oxide (NO): a feature of its antidepressant
      activity?
AB  - Voltammetric (electrochemical) methodologies such as differential pulse
      voltammetry and amperometry used together with electrically and chemically
      treated carbon fibre micro-electrodes (mCFE) allow selective monitoring of nitric
      oxide (NO). Preliminary in vitro studies have shown that the selective serotonin
      reuptake inhibitor (SSRI) antidepressant paroxetine inhibits constitutive nitric
      oxide synthase (cNOS) activity in animals and humans and that another SSRI such
      as fluoxetine reduced NO release in the media of synovial cells. The aim of this
      work was to verify by means of amperometry and specifically treated mCFE the
      capability of fluoxetine to alter the in vivo release of central NO, in the
      attempt to further clarify such putative antidepressant mechanism of action of
      this SSRI compound. The in vivo results support the chemical NO related nature of
      the endogenous amperometric signal evoked by NMDA injection in the striatum of
      anaesthetised rats, as pre-treatment with NOS inhibitor l-NAME prevented its
      appearance. Subsequently fluoxetine treatment resulted in decreased striatal NO,
      further supporting in vitro studies proposing a link between the serotonergic
      system and the NO system.

PMID- 20036715
TI  - Tactile/proprioceptive integration during arm localization is intact in
      individuals with Parkinson's disease.
AB  - It has been theorized that sensorimotor processing deficits underlie Parkinson's
      disease (PD) motor impairments including movement under proprioceptive control.
      However, it is possible that these sensorimotor processing deficits exclude
      tactile/proprioception sensorimotor integration: prior studies show improved
      movement accuracy in PD with endpoint tactile feedback, and good control in
      tactile-driven precision-grip tasks. To determine whether tactile/proprioceptive
      integration in particular is affected by PD, nine subjects with PD (off
      medication, UPDRS motor=19-42) performed an arm-matching task without visual
      feedback. In some trials one arm touched a static tactile cue that conflicted
      with dynamic proprioceptive feedback from biceps brachii muscle vibration. This
      sensory conflict paradigm has characterized tactile/proprioceptive integration in
      healthy subjects as specific to the context of tactile cue mobility assumptions
      and the intention to move the arm. We found that the individuals with PD had
      poorer arm-matching accuracy than age-matched control subjects. However, PD-group
      accuracy improved with tactile feedback. Furthermore, sensory conflict conditions
      were resolved in the same context-dependent fashion by both subject groups. We
      conclude that the somatosensory integration mechanism for prioritizing tactile
      and proprioception feedback in this task are not disrupted by PD, and are not
      related to the observed proprioceptive deficits.

PMID- 20036716
TI  - Functional expression of a large-conductance Ca2+-activated K+ channel in mouse
      substantia nigra pars compacta dopaminergic neurons.
AB  - The existence of large-conductance Ca(2+)-activated K(+) (BK) channels in
      substantia nigra pars compacta (SNc) has been a matter of debate. Using the patch
      clamp technique in the inside-out configuration, we have recorded BK channel
      currents in SNc dopaminergic neurons. The channel has a conductance of 301 pS
      with a slight inward rectification and is both voltage- and calcium-dependent.
      Paxilline, a specific BK channel blocker, can completely block the channel, while
      tetraethylammonium (TEA), a nonspecific blocker of voltage-gated potassium
      channels, reduces its conductance and a high concentration of TEA (30 mM)
      inhibits its activity. ATP and GTP reduce the channel activity, while ADP is less
      potent, and AMP has no effect. The channel is also sensitive to changes in
      intracellular pH. Our results indicate that functional BK channels are expressed
      in SNc and suggest the possibility that the BK channel may be involved in the
      response of SNc dopaminergic neurons to metabolic stress.

PMID- 20036717
TI  - Cerebellar neurometabolite abnormalities in pediatric attention/deficit
      hyperactivity disorder: a proton MR spectroscopic study.
AB  - We designed a case-control proton magnetic resonance spectroscopic study
      comparing the cerebellar and prefrontal regions of a group of 17 ADHD (attention
      deficit/hyperactivity disorder) medicated children and a group of 17 control
      children matched for laterality, gender and age. As we had found decreased gray
      matter volume in the right prefrontal region and the left cerebellar hemisphere
      in a previous voxel-based morphometry study conducted on an independent ADHD
      sample, we tested the hypothesis that these regions should show neurometabolite
      abnormalities. MRI (magnetic resonance imaging) was performed with a 1.5 T
      system; spectral acquisition was performed with a single-voxel technique and a
      PRESS sequence. Two volumes of interest were selected in the right prefrontal
      region and the left cerebellar hemisphere. NAA (N-acetylaspartate), Cre
      (creatine), Cho (choline), MI (myo-inositol) and Glx (glutamate-glutamine)
      resonance intensities were absolutely quantified. In the left cerebellar
      hemisphere, ADHD children showed significant decreased MI and NAA absolute
      concentrations with high effect sizes (p=0.004, ES=1.184; p=0.001, ES=1.083). The
      diminished absolute concentration of the NAA could be related to a gray matter
      volume decrease in the same cerebellar region found in the previous voxel-based
      morphometry MRI study, while the reduced MI absolute concentration could express
      a decreased glial density. This is the first proton MR spectroscopic study
      examining the cerebellum and it provides additional support for the role of
      cerebellum in the ADHD neurobiology.

PMID- 20036718
TI  - Cloning and molecular characterization of Dashurin encoded by C20orf116, a PCI
      domain containing protein.
AB  - BACKGROUND: Characterization of gene products originating from undefined open
      reading frames and delineation of biological functions has become the task after
      the human genome has been decoded. METHODS: We cloned the human C20orf 116 and
      defined its transcript in liver, kidney and various brain regions by Northern
      analysis. Antibodies against recombinant protein used for immunofluorescence and
      immunoblots confirmed its expression in these tissues. With the focus on kidney,
      its tubular expression and presence in glomerula were shown. RESULTS: A 28 aa
      long signal peptide predicted by in silico analysis is reflected by visualization
      of size variants of approximately 3kDa difference suggesting a signal peptidase
      cleavage of the proform. Cell compartment separation confirmed the presence of
      Dashurin in peroxisomes/mitochondria, microsomes, cytosol and nucleus. This is in
      line with green fluorescent protein (GFP)-Dashurin fusion protein shuttling
      between cytosol and nucleus. Luciferase reporter studies revealed a 2-3 fold
      increase of promoter activities upon over-expression. Bioinformatic analysis
      identified a PCI-domain at the C-terminus providing protein-protein interaction
      capabilities. CONCLUSION: Our present findings suggest the involvement of
      Dashurin in gene transcription or mRNA translation. GENERAL SIGNIFICANCE:
      Dashurin shares the PCI-domain with three multisubunit protein complexes (26S
      proteasome, COP9 signalosome and eIF3 translation initiation factor).

PMID- 20036719
TI  - Cortico-cerebellar coherence and causal connectivity during slow-wave activity.
AB  - Cerebral cortical slow-wave activity (SWA) is prominent during sleep and also
      during ketamine-induced anesthesia. SWA in electroencephalogram (EEG) recordings
      is closely linked to prominent fluctuations between up- and down-states in the
      membrane potential of pyramidal neurons. However, little is known about how the
      cerebellum is linked into SWA and whether slow cortical oscillations influence
      sensory cerebellar responses. To examine these issues, we simultaneously recorded
      EEG activity from the cerebral cortex (SI, MI, and supplementary motor area
      (SMA)), local field potentials at the input stage of cerebellar processing in the
      cerebellar granule cell layer (GCL) and inferior olive (IO), and single unit
      activity at the output stage of the cerebellum in the deep cerebellar nuclei
      (DCN). We found that in ketamine-anesthetized rats, SWA was synchronized between
      all recorded cortical areas and was phase locked with local field potentials of
      the GCL, IO and single unit activity in the DCN. We also found that cortical up
      states are linked to activation of GCL neurons but to inhibition of cerebellar
      output from the DCN, with the latter an effect likely mediated by Purkinje cells.
      A partial coherence analysis showed further that a large portion of SWA shared
      between GCL and DCN was transmitted from the cortex, since the coherence shared
      between GCL and DCN was diminished when the effect of cortical activity was
      subtracted. To determine the causal flow of information between structures, a
      directed transfer function was calculated between the simultaneous activities of
      SI, MI, SMA, GCL and DCN. This analysis demonstrated that the primary direction
      of information flow was from cortex to the cerebellum and that SI had a stronger
      influence than other cortical areas on DCN activity. The strong functional
      connectivity with SI in particular is in agreement with previous findings of a
      strong cortical component in cerebellar sensory responses.

PMID- 20036720
TI  - Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated
      protein kinase and sequestosome 1 stress protein.
AB  - This study evaluated the protective role of p38 mitogen-activated protein kinase
      (p38 MAPK) inhibitors and sequestosome 1 (Sqstm1/A170/p62), a stress-induced
      signal modulator, in acoustic injury of the cochlea in mice. Two weeks after the
      exposure of mice to acoustic stress, threshold shifts of the auditory brainstem
      response (ABR) from the pre-exposure level and hair cell loss were evaluated. The
      activation of p38 MAPK was observed in cochlea by immunostaining 4 h after
      acoustic stress. To examine the role of p38 MAPK in tissue injury, its inhibitors
      were i.p. injected into male wild-type C57BL mice before the acoustic
      overexposure. The inhibitors SB202190 and SB203580 but not the inactive analogue
      SB202474 dose-dependently decreased the auditory threshold shift and outer hair
      cell loss induced by acoustic overexposure, suggesting the involvement of p38
      MAPK in ototoxicity. We found that acoustic overexposure induced the up
      regulation of Sqstm1 mRNA expression in the cochlea of wild-type mice and that
      SQSTM1-deficient mice exhibited an enhanced ABR threshold shift and hair cell
      loss, suggesting a role of SQSTM1 in the protection of tissue from acoustic
      stress.

PMID- 20036721
TI  - Micronucleus frequency in buccal mucosa cells of mobile phone users.
AB  - Mobile phones are being used extensively throughout the world, with more than
      four billion accounts existing in 2009. This technology applies electromagnetic
      radiation in the microwave range. Health effects of this radiation have been
      subject of debate for a long time, both within the scientific community and
      within the general public. This study investigated the effect of mobile phone use
      on genomic instability of the human oral cavity's mucosa cells. 131 Individuals
      donated buccal mucosa cells extracted by slightly scraping the oral cavity with a
      cotton swab. Every participant filled out a questionnaire about mobile phone use
      including duration of weekly use, overall period of exposure and headset usage.
      13 Individuals did not use mobile phones at all, 85 reported using the mobile
      phone for three hours per week or less, and 33 reported use of more than three
      hours per week. Additionally, information on age, gender, body weight, smoking
      status, medication and nutrition was retrieved. For staining of the cells a
      procedure using alpha-tubulin-antibody and chromomycin A(3) was applied.
      Micronuclei and other markers were evaluated in 1000 cells per individual at the
      microscope. A second scorer counted another 1000 cells, resulting in 2000
      analyzed cells per individual. Mobile phone use did not lead to a significantly
      increased frequency of micronuclei.

PMID- 20036722
TI  - 5-Fluorouracil acetic acid/beta-cyclodextrin conjugates: drug release behavior in
      enzymatic and rat cecal media.
AB  - 5-Fluorouracil-1-acetic acid (5-FUA) was prepared and covalently conjugated to
      beta-cyclodextrin (beta-CyD) through ester or amide linkage, and the drug release
      behavior of the conjugates in enzymatic solutions and rat cecal contents were
      investigated. The 5-FUA/beta-CyD ester conjugate was slowly hydrolyzed to 5-FUA
      in aqueous solutions (half lives (t(1/2))=38 and 17h at pH 6.8 and 7.4,
      respectively, at 37 degrees C), whereas the amide conjugate was hardly hydrolyzed
      at these physiological conditions, but hydrolyzed only in strong alkaline
      solutions (>0.1M NaOH) at 60 degrees C. Both ester and amide conjugates were
      degraded in solutions of a sugar-degrading enzyme, alpha-amylase, to 5
      FUA/maltose and triose conjugates, but the release of 5-FUA was only slight in
      alpha-amylase solutions. In solutions of an ester-hydrolyzing enzyme, carboxylic
      esterase, the ester conjugate was hydrolyzed to 5-FUA at the same rate as that in
      the absence of the enzyme, whereas the amide conjugate was not hydrolyzed by the
      enzyme. On the other hand, 5-FUA was rapidly released when the ester conjugate
      was firstly hydrolyzed by alpha-amylase, followed secondly by carboxylic
      esterase. The results indicated that the ester conjugate was hydrolyzed to 5-FUA
      in a consecutive manner, i.e. it was firstly hydrolyzed to the small saccharide
      conjugates, such as the maltose conjugate, by alpha-amylase, and the resulting
      small saccharide conjugates having less steric hindrance was susceptible to the
      action of carboxylic esterase, giving 5-FUA. The in vitro release behavior of the
      ester conjugate was clearly reflected in the hydrolysis in rat cecal contents and
      in the in vivo release after oral administration to rats.

PMID- 20036723
TI  - Intermittent exposure with moderate-level sound impairs central auditory function
      of mature animals without concomitant hearing loss.
AB  - Long-term, passive, continuous exposure of mature animals to moderate-level, band
      limited sounds can profoundly decrease neural activity in primary auditory cortex
      (AI) to sounds in the exposure frequency range, and increase activity to sounds
      outside the exposure range. The resulting reorganization of the AI tonotopic map
      resembles that following a restricted lesion of the cochlear epithelium. Here we
      show qualitatively similar effects of passive exposure when it is limited to 12
      h/day, simulating a noisy-work/quiet-living environment, albeit at substantially
      lower intensity levels (68 dB SPL) than are considered harmful to hearing.
      Compared to continuous exposure at the same SPL and over a similar duration (6-12
      weeks), this intermittent exposure produced a smaller decrease in AI spike and
      LFP (local field potential) activity in response to sound frequencies in the
      exposure range, and an increase in activity only for frequencies above the
      exposure range. As expected at these exposure levels, cortical changes occurred
      in the absence of concomitant hearing loss (i.e., absolute threshold shifts). Our
      results have implications for occupational noise exposure standards, which
      presently may not prevent changes in central auditory function that cannot be
      detected on the standard behavioral audiogram.

PMID- 20036724
TI  - Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: involvement of
      Akt and Erk.
AB  - AIM OF THE STUDY: The final goal of this work was to study the toxic and
      apoptosis effects induced by fractions from Ganoderma lucidum [Ganoderma lucidum
      (Curtis) P. Karst.; Ganodermataceae Donk] on NB4 human leukemia cells. MATERIALS
      AND METHODS: Two aqueous extracts and a methanol-extracted column-chromatography
      semipurified fraction were obtained from Ganoderma lucidum fruiting body. Flow
      cytometry analyses were used to measure cell viability, cell cycle and DNA
      fragmentation and to quantify apoptosis. Western-blot analyses were used to
      quantify changes in apoptosis proteins and intracellular kinases. RESULTS:
      Aqueous extracts slightly reduce cell viability and induce DNA fragmentation in
      NB4 cells. Methanol-extracted semipurified fraction at dilutions down to 15% or
      40% of the initial fraction concentration reduced significantly the viability of
      these leukemia cells (treated for 19h) with induction of DNA fragmentation and
      induction of apoptosis. Overmore, the dilution down to 15% of the initial E3
      concentration induced a reduction of p53 levels, of the Bcl2/Bax relationship as
      well as reduced levels of both unphosphorylated and phosphorylated Akt (Protein
      kinase Akt, protein kinase B) and Erk (Erk1 and 2). CONCLUSIONS: Induction of
      apoptosis and alterations in signal transduction kinases (Akt and Erk) are
      produced by active fractions from Ganoderma lucidum on human leukemia cells.
      These data could be of important relevance from the viewpoint of antitumor
      actions of compounds from Ganoderma lucidum. Eventual therapy applications in
      leukemia cells might be developed.

PMID- 20036725
TI  - Gene expression profiling implicates OXPHOS complexes in lifespan extension of
      flies over-expressing a small mitochondrial chaperone, Hsp22.
AB  - Aging is a complex process accompanied by a decreased capacity to tolerate and
      respond to various stresses. Heat shock proteins as part of cell defense
      mechanisms are up-regulated following stress. In Drosophila, the mitochondrial
      Hsp22 is preferentially up-regulated in aged flies. Its over-expression results
      in an extension of lifespan and an increased resistance to stress. Hsp22 has
      chaperone-like activity in vitro, but the mechanism(s) by which it increases
      lifespan in flies are unknown. Genome-wide analysis was performed on long-lived
      Hsp22+ and control flies to unveil transcriptional changes brought by Hsp22.
      Transcriptomes obtained at 45days, 90% and 50% survival were then compared
      between them to focus more on genes up- or down-regulated in presence of higher
      levels of hsp22 mRNA. Hsp22+ flies display an up-regulation of genes mainly
      related to mitochondrial energy production and protein biosynthesis, two
      functions normally down-regulated during aging. Interestingly, among the 26 genes
      up-regulated in Hsp22+ flies, 7 genes encode for mitochondrial proteins, 5 of
      which being involved in OXPHOS complexes. Other genes that could influence aging
      such as CG5002, dGCC185 and GstS1 also displayed a regulation linked to Hsp22
      expression. The up-regulation of genes of the OXPHOS system in Hsp22+ flies
      suggest that mitochondrial homeostasis is at the center of Hsp22 beneficial
      effects on lifespan.

PMID- 20036726
TI  - In vitro determination of tetanus toxicity by an endopeptidase assay linked to a
      ganglioside-binding step.
AB  - Assays for the detection of tetanus neurotoxin (TeNT) are relevant for research
      applications as well as for the safety testing of tetanus vaccines. So far, these
      assays are usually performed as toxicity tests in guinea pigs or mice. The
      alternative methods described to date were mostly based on the detection of the
      toxin's proteolytic activity. However, these endopeptidase assays turned out to
      be unreliable because they only measure the enzymatic activity as sole
      determinant of tetanus toxicity, while not taking into account other parameters
      like the toxin's capacity to bind to target cells. In order to better reflect the
      in vivo situation of a tetanus infection, we have linked an endopeptidase assay
      to a ganglioside-binding step. The resulting method, which offers a unique
      combination of two functionally linked assays, detects those TeNT molecules only
      which possess both a functional binding domain as well as an active enzymatic
      domain. Our results demonstrate that this assay is able to reliably detect TeNT,
      and therefore might provide a basis for the replacement of the animal tests for
      detection of tetanus toxicity. Moreover, the assay concept could also be useful
      for in vitro toxicity measurements of other toxins with similar subunit
      structures.

PMID- 20036727
TI  - Aflatoxin B1 modulates the insulin-like growth factor-2 dependent signaling axis.
AB  - Although aflatoxin B(1) (AFB(1)) is known as a mycotoxin that induces
      hepatocellular carcinoma (HCC), its effects on HCC cells have not been
      sufficiently investigated. The HCC cell lines HepG2, Huh-6, Huh-7, and PLC were
      cultured (5 x 10(5)cells/ml) and various concentrations of AFB(1) were added. The
      expression levels of the alpha-fetoprotein (AFP), insulin-like growth factor-2
      (IGF-2), and insulin-like growth factor-1 receptor (IGF-1R) genes in each sample
      were determined by real-time PCR, with the following results: (1) The level of
      AFP expression in HepG2 increased at 5-50 ng/ml of AFB(1) in a dose-dependent
      manner. The AFP expression level in Huh-6 increased at 0.01-5 ng/ml of AFB(1) in
      a dose-dependent manner and decreased to half controls level at 50 ng/ml of
      AFB(1). The AFP expression level in Huh-7 decreased to one-third the original
      level at 0.5-50 ng/ml of AFB(1). The AFP expression level in PLC decreased at 0
      0.5 ng/ml of AFB(1) in a dose-dependent manner, and decreased to one-third at
      concentrations of AFB(1) between 0.5 and 50 ng/ml. (2) The IGF-2 and IGF-1R
      expression levels in Huh-6 increased more than 10-fold at 0.5-5 ng/ml of AFB(1),
      but decreased to half at 50 ng/ml of AFB(1). The IGF-2 and IGF-1R expression
      levels in other cell lines increased in a dose-dependent manner. AFB(1) induced
      translations of IGF-2 and IGF-1R and cell proliferation: When 50 ng/ml AFB(1) was
      administrated, cell numbers were 2.0-, 1.7-, and 1.5-fold higher than those of
      controls after 3 days of culture in HepG2, Huh-7, and PLC, respectively.
      Particularly, in Huh-6, it increased 2.5-fold higher than those of controls
      following 5 ng/ml AFB(1) administration. The ratio of fold-change phospho-IGF-1R
      in all cell lines that were treated with AFB(1), increased 1.1-1.5-fold. These
      results indicate that AFB(1) may enhance HCC cell proliferation through an IGF-2
      dependent signal axis, although it remains to be investigated whether those
      effects are associated with human hepatocarcinogenesis resulting from AFB(1)
      exposure.

PMID- 20036728
TI  - Cooperation and coordination among scientists from cellular, molecular, and
      computational disciplines will not only complement, but will be essential to,
      such a shift.

PMID- 20036729
TI  - Does potassium sorbate induce genotoxic or mutagenic effects in lymphocytes?
AB  - The present study evaluates the genotoxic potential of potassium sorbate (PS) in
      cultured and isolated human lymphocytes. To assess the damage caused by PS in
      humans, we designed in vitro experiments by measuring chromosomal aberrations
      (CAs), sister-chromatid exchanges (SCEs), micronucleus (MN) and comet assays.
      Lymphocytes were treated with negative control (sterile distilled water),
      positive control (MMC for cultured lymphocytes, and H(2)O(2) for isolated
      lymphocytes) and four concentrations (125, 250, 500, and 1000 microg/ml) of PS.
      According to the results, PS treatment significantly increases the CAs (with or
      without gaps at 500 and 1000 microg/ml concentrations) and SCEs (at 250, 500,
      1000 microg/ml for 24h and 125, 250, 500, 1000 microg/ml for 48h) compared with
      vehicle control. Following treatment of the isolated lymphocytes for 1h,
      significant PS-induced DNA strand breaks were observed, at all concentrations.
      However, PS failed to significantly affect the MN assay. On the contrary, PS does
      not cause cell cycle delay as noted by the non-significant decrease in the
      cytokinesis-block proliferation index (CBPI) and replicative index (RI). Only a
      slight decrease was observed in the mitotic index (MI) at the highest
      concentration for both treatment times. From the results, PS is clearly seen to
      be genotoxic to the human peripheral blood lymphocytes in vitro.

PMID- 20036730
TI  - Inability to confirm estrogenicity of the heterocyclic amine PhIP in two in vitro
      assays.
AB  - 2-Amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) is a heterocyclic amine
      which is found in food after cooking and which is a known mutagen. Reports from
      several laboratories have proposed that PhIP has estrogenic activity, which would
      classify PhIP as a xenoestrogen with human exposure via food. We tested PhIP in
      two cell-based assays for estrogenicity, both based on human cell lines but
      utilising different outcome measures: ERLUX (reporter-gene activation) and
      ESCREEN (cell proliferation). PhIP was inactive in both assays at concentrations
      spanning the picomolar to micromolar range. To eliminate supplier differences as
      an explanation for the disparity between these results and positive findings in
      the literature, we purchased PhIP from three suppliers and found no detectable
      estrogenic activity in any batch. (1)H NMR spectroscopy confirmed the chemical
      identity of the tested stock solutions. Correct assay performance was confirmed
      by including positive and vehicle controls on every assay plate, and by
      demonstrating the expected responses to a panel of known estrogens (estradiol,
      bisphenol A, and genistein). Our results differ from those in the literature and,
      whilst the exact reason for this is unknown, we discuss possible explanations of
      the disparity. Our results provide no in vitro evidence for the classification of
      PhIP as an estrogen.

PMID- 20036731
TI  - Effects of Roundup and glyphosate formulations on intracellular transport,
      microtubules and actin filaments in Xenopus laevis melanophores.
AB  - Glyphosate containing herbicides, such as Roundup, are commonly used and
      generally considered to be safe. However, some toxic effects are found on
      amphibians in vivo and human and mouse cells in vitro. In this study the effects
      of Roundup, glyphosate, glyphosateisopropylamine and isopropylamine were studied
      on intracellular transport by measuring aggregation capacity in Xenopus laevis
      melanophores. The chemicals inhibited retrograde transport of melanosomes in the
      range of 0.5-5mM. Cellular morphology and localization of microtubules and actin
      filaments were affected as determined by immunocytochemistry. Both glyphosate and
      Roundup decreased pH in the media. Acidic pH inhibited melanosome transport and
      altered microtubule and actin morphology in the absence of chemicals, while
      transport inhibiting concentrations of glyphosate, Roundup and
      glyphosateisopropylamine disassembled both microtubules and actin filaments. At
      physiological pH the effects of Roundup decreased whereas glyphosate failed to
      inhibit transport. Physiological pH decreases glyphosate lipophilicity and its
      diffusion into the cytoplasm. The Roundup formulation contains surfactants, such
      as POEA (polyetylated tallow amine) that increases membrane permeability allowing
      cellular uptake at physiological pH. Our results show that the effects of
      glyphosate containing compounds are pH-dependent and that they inhibit
      intracellular transport through disassembly of the cytoskeleton possibly by
      interfering with intracellular Ca(2+)-balance.

PMID- 20036732
TI  - Evaluation of cytochrome P450 1 (CYP1) and N-acetyltransferase 1 (NAT1)
      activities in HaCaT cells: implications for the development of in vitro
      techniques for predictive testing of contact sensitizers.
AB  - Xenobiotic metabolizing enzymes like cytochrome P450s and N-acetyltransferase are
      expressed in keratinocytes and professional antigen-presenting cells. Thus,
      biotransformation of chemicals applied to the skin can be relevant for their
      potential to cause skin toxicity and immune responses like allergic contact
      dermatitis. Considering the keratinocyte cell line HaCaT as a relevant in vitro
      tool for epidermal biotransformation, we specifically investigated CYP1 (EROD)
      and N-acetyltransferase 1 (NAT1) activities of three different HaCaT shipments
      and human primary keratinocytes (NHEK). Solvent treated HaCaT showed EROD levels
      near the detection limit (0.047 pmol/mg/min), primary keratinocytes (n=4) were in
      a range between 0 and 0.76 pmol/mg/min. B[a]P (1 microM) induced EROD activities
      of 19.0+/-0.9 pmol/mg/min (n=11) in HaCaT and 5.8+/-0.5 pmol/mg/min (n=4) in
      NHEK. N-acetylation activities for para-aminobenzoic acid (PABA) were in average
      3.4-fold higher in HaCaT compared to NHEK (8+/-0.5 nmol/mg/min) and varied
      between the HaCaT shipments (range 12.0-44.5 nmol/mg/min). This was in good
      agreement with NAT1 promoter P1 dependent mRNA level and N-acetylation of the
      contact allergen para-phenylenediamine (PPD) under typical cell-based assay
      conditions. We conclude that HaCaT represent a suitable in vitro model for
      studying the qualitative contribution of epidermal phase1/phase2 metabolism to
      toxicological endpoints such as skin sensitization.

PMID- 20036733
TI  - Photoinflammatory responses to UV-irradiated ketoprofen mediated by the induction
      of ROS generation, enhancement of cyclooxygenase-2 expression, and regulation of
      multiple signaling pathways.
AB  - Ketoprofen (KP) is photolabile and undergoes degradation when irradiated by
      sunlight, causing the development of various skin diseases. In this study, we
      found that UVB-irradiated KP can lead to inflammatory responses mediated by the
      induction of COX-2 and production of PGE(2). The ability of cells to repair UVB
      induced cyclobutane pyrimidine dimers was impaired by UVB-irradiated KP, which
      consequently facilitated UVB-induced DNA damage to keratinocytes. The reactive
      oxygen species (ROS) generated by the photodegradation of KP facilitate UVB
      induced inflammation and apoptosis in HaCaT cells. Elevation of the COX-2 levels
      was inhibited by an NADPH oxidase inhibitor and an NF-kappaB inhibitor but was
      largely enhanced after glutathione depletion by buthionine sulfoximine.
      Inhibition of ERK1/2, p38, and PI3K signaling attenuated the induction of COX-2,
      whereas inhibition of JNK signaling by SP600125 had very little effect. UVB
      irradiated KP provoked an appreciable accumulation of pSer(15)-p53/COX-2
      complexes, but this nuclear association of complexes was partially inhibited by
      PD98059. Silencing of COX-2 with siRNA was associated with reduced p53
      phosphorylation and enhanced KP-photoinduced loss of mitochondrial membrane
      potential and cleavage of caspase 3 and PARP. This induction of apoptosis was
      prevented by N-acetylcysteine. In conclusion, this study highlights the
      particular inflammatory response to a photooxidative drug and suggests that KP
      photoinduced inflammatory responses are predominantly attributable to induction
      of ROS generation and directly impair DNA repair.

PMID- 20036734
TI  - Superoxide anion and proteasomal dysfunction contribute to curcumin-induced
      paraptosis of malignant breast cancer cells.
AB  - Curcumin is considered a pharmacologically safe agent that may be useful in
      cancer chemoprevention and therapy. Here, we show for the first time that
      curcumin effectively induces paraptosis in malignant breast cancer cell lines,
      including MDA-MB-435S, MDA-MB-231, and Hs578T cells, by promoting vacuolation
      that results from swelling and fusion of mitochondria and/or the endoplasmic
      reticulum (ER). Inhibition of protein synthesis by cycloheximide blocked curcumin
      induced vacuolation and subsequent cell death, indicating that protein synthesis
      is required for this process. The levels of AIP-1/Alix protein, a known inhibitor
      protein of paraptosis, were progressively downregulated in curcumin-treated
      malignant breast cancer cells, and AIP-1/Alix overexpression attenuated curcumin
      induced death in these cells. ERK2 and JNK activation were positively associated
      with curcumin-induced cell death. Mitochondrial superoxide was shown to act as a
      critical early signal in curcumin-induced paraptosis, whereas proteasomal
      dysfunction was mainly responsible for the paraptotic changes associated with ER
      dilation. Notably, curcumin-induced paraptotic events were not observed in normal
      breast cells, including mammary epithelial cells and MCF-10A cells. Taken
      together, our findings on curcumin-induced paraptosis may provide novel insights
      into the mechanisms underlying the selective anti-cancer effects of curcumin
      against malignant cancer cells.

PMID- 20036735
TI  - Impairment of mitochondrial respiratory chain activity in aortic endothelial
      cells induced by glycated low-density lipoprotein.
AB  - Coronary artery disease (CAD) is the leading cause of mortality in diabetic
      patients. Mitochondrial dysfunction and increased production of reactive oxygen
      species (ROS) are associated with diabetes and CAD. Elevated levels of glycated
      LDL (glyLDL) were detected in patients with diabetes. Our previous studies
      demonstrated that glyLDL increased the generation of ROS and altered the
      activities of antioxidant enzymes in vascular endothelial cells (EC). This study
      examined the effects of glyLDL on oxygen consumption in mitochondria and the
      activities of key enzymes in the mitochondrial electron transport chain (ETC) in
      cultured porcine aortic EC. The results demonstrated that glyLDL treatment
      significantly impaired oxygen consumption in Complexes I, II/III, and IV of the
      mitochondrial ETC in EC compared to LDL or vehicle control detected using
      oxygraphy. Incubation with glyLDL significantly reduced the mitochondrial
      membrane potential, the NAD(+)/NADH ratio, and the activities of mitochondrial
      ETC enzymes (NADH-ubiquinone dehydrogenase, succinate cytochrome c reductase,
      ubiquinone cytochrome c reductase, and cytochrome c oxidase) in EC compared to
      LDL or control. The abundance of mitochondria-associated ROS and the release of
      ROS from EC were significantly increased after glyLDL treatment. The findings
      suggest that glyLDL attenuates the activities of key enzymes in the mitochondrial
      ETC, decreases mitochondrial oxygen consumption, reduces mitochondrial membrane
      potential, and increases ROS generation in EC, which potentially contribute to
      mitochondrial dysfunction in diabetic patients.

PMID- 20036737
TI  - HpSulf, a heparan sulfate 6-O-endosulfatase, is involved in the regulation of
      VEGF signaling during sea urchin development.
AB  - Cell surface heparan sulfate proteoglycans (HSPGs) play significant roles in the
      regulation of developmental signaling, including vascular endothelial growth
      factor (VEGF), fibroblast growth factor, Wnt and bone morphogenetic protein
      signaling, through modification of their sulfation patterns. Recent studies have
      revealed that one of the functions of heparan sulfate 6-O-endosulfatase (Sulf) is
      to remove the sulfate from the 6-O position of HSPGs at the cell surface, thereby
      regulating the binding activities of heparan sulfate (HS) chains to numerous
      ligands and receptors in animal species. In this study, we focused on the sea
      urchin Hemicentrotus pulcherrimus homolog of Sulf (HpSulf), and analyzed its
      expression pattern and functions during development. HpSulf protein was present
      throughout development and localized at cell surface of all blastomeres. In
      addition, the HS-specific epitope 10E4 was detected at the cell surface and
      partially colocalized with HpSulf. Knockdown of HpSulf using morpholino antisense
      oligonucleotides (MO) caused abnormal morphogenesis, and the development of MO
      injected embryos was arrested before the hatched blastula stage, indicating that
      HpSulf is necessary for the early developmental process of sea urchin embryos.
      Furthermore, we found that injection of HpSulf mRNA suppressed the abnormal
      skeleton induced by overexpression of HpVEGF mRNA, whereas injection of an
      inactive form of HpSulf mRNA, containing mutated cysteines in the sulfatase
      domain, did not have this effect. Taken together, these results suggest that
      HpSulf is involved in the regulation of various signal transductions, including
      VEGF signaling, during sea urchin development.

PMID- 20036738
TI  - Enzyme-assisted synthesis and structural characterization of pure benzodiazepine
      glucuronide epimers.
AB  - The three hydroxybenzodiazepines oxazepam, temazepam, and lorazepam used for
      their anxiolytic, sedative, and anticonvulsant properties are metabolized by
      glucuronidation, which is the predominant pathway in the clearance mechanism of
      exogenous and endogenous substances during phase II metabolism. The aim of this
      study was the synthesis of benzodiazepine-O-glucuronides as analytical reference
      substances. All benzodiazepines are prescribed clinically as racemic
      formulations. The resulting conjugates from the coupling reactions with
      glucuronic acid are epimeric pairs of glucuronides. Due to the importance of
      stereochemical factors in drug disposition it is necessary to separate the
      diastereomeric forms after synthesis. An enzyme-assisted synthesis was developed
      and optimized by using microsomal UGT from fresh swine liver to receive
      multimilligram amounts of the benzodiazepine glucuronides, which were not
      accessible by standard synthetic procedures, like the Koenigs-Knorr- and
      Williamson-ether-synthesis. Swine liver microsomes were prepared by
      homogenization and differential centrifugation of liver tissue. In the presence
      of liver microsomes the benzodiazepines and cofactor UDPGA were incubated for
      24h. After incubation the microsomes were removed by protein precipitation and
      the residual benzodiazepines by liquid-liquid extraction (dichloromethane). The
      epimeric pairs of benzodiazepine glucuronides were separated by preparative high
      performance liquid chromatography (HPLC) followed by solid phase extraction (SPE)
      to obtain the pure benzodiazepine glucuronide epimers. The synthesis products
      were characterized by mass spectroscopy and nuclear magnetic resonance (NMR)
      spectroscopy.

PMID- 20036739
TI  - Crystallization and polymorphic transitions of chlorpropamide in aqueous 2
      hydroxybutyl-beta-cyclodextrin solution.
AB  - Effects of cyclodextrins on crystallization of chlorpropamide and the polymorphic
      transition mechanism of the drug in aqueous solution were investigated. In the
      presence of 2-hydroxybutyl-beta-cyclodextrin, chlorpropamide was exclusively
      crystallized to metastable Form II and III polymorphs, whereas it was
      crystallized to stable Form A in the absence of the beta-cyclodextrin at 4
      degrees C. The crystallization to metastable Form II or III polymorph was
      dependent upon 2-hydroxybutyl-beta-cyclodextrin concentrations employed, i.e.
      crystallization to Form III at a lower concentration (0.5 mM), whereas to Form II
      in a higher concentration (5 mM). At an intermediate concentration (2 mM), the
      least stable Form II crystal was initially precipitated, but it was transformed
      to Form III crystal. At higher temperature, Form III crystal was converted to
      stable Form A crystal. In aqueous solution, chlorpropamide crystallized to stable
      Form A crystal consecutively through metastable Forms II and III, according to
      "Ostwald's Rule of Stages". 2-Hydroxybutyl-beta-cyclodextrin inhibits the
      transition of Form II to Form III at higher concentrations and that of Form III
      to Form A at lower concentrations. The results suggest that 2-hydroxybutyl-beta
      cyclodextrin is useful for selective preparation of metastable chlorpropamide
      polymorphs occurring during crystallization according to the Ostwald's rule.

PMID- 20036736
TI  - Update on the oxidative stress theory of aging: does oxidative stress play a role
      in aging or healthy aging?
AB  - The oxidative stress theory of aging predicts that manipulations that alter
      oxidative stress/damage will alter aging. The gold standard for determining
      whether aging is altered is life span, i.e., does altering oxidative
      stress/damage change life span? Mice with genetic manipulations in their
      antioxidant defense system designed to directly address this prediction have,
      with few exceptions, shown no change in life span. However, when these
      transgenic/knockout mice are tested using models that develop various types of
      age-related pathology, they show alterations in progression and/or severity of
      pathology as predicted by the oxidative stress theory: increased oxidative stress
      accelerates pathology and reduced oxidative stress retards pathology. These
      contradictory observations might mean that (a) oxidative stress plays a very
      limited, if any, role in aging but a major role in health span and/or (b) the
      role that oxidative stress plays in aging depends on environment. In environments
      with minimal stress, as expected under optimal husbandry, oxidative damage plays
      little role in aging. However, under chronic stress, including pathological
      phenotypes that diminish optimal health, oxidative stress/damage plays a major
      role in aging. Under these conditions, enhanced antioxidant defenses exert an
      "antiaging" action, leading to changes in life span, age-related pathology, and
      physiological function as predicted by the oxidative stress theory of aging.

PMID- 20036740
TI  - Peripheral neuroactive steroids may be as good as the steroids in the
      cerebrospinal fluid for the diagnostics of CNS disturbances.
AB  - To compare the predictivity of the neuroactive steroids in the cerebrospinal
      fluid and peripheral blood for the diagnostics of CNS disturbances, eighteen
      unconjugated steroids were quantified in the cerebrospinal fluid (CSF) from the
      3rd ventricle and 18 unconjugated steroids and 7 steroid polar conjugates were
      measured in the serum using GC-MS and RIA. Eight postmenopausal women (56-78
      years of age) and 7 men (22-88 years of age) with hydrocephalus were enrolled in
      the study. The sensitivity of the method ranged from low femtogram to low
      picogram levels depending on the steroid fragmentation pattern. Using
      multivariate regression, a model for simultaneous prediction of the CSF steroids
      from the serum steroids was completed. Then, the penetrability of the individual
      steroids across the blood-brain-barrier was evaluated and the sources of various
      brain steroids were estimated. Our data show that a part of the steroids may be
      synthesized de novo in the CNS. However, substantial part of the steroid
      metabolites may be synthesized in the CNS from the steroid precursors or directly
      transported from the periphery. The CNS in situ synthesis and transport from
      periphery might be complementary in some cases, i.e. brain synthesis might
      provide minimum level of steroids, which are indispensable for the CNS functions.

PMID- 20036741
TI  - Molecular and biochemical analysis of an aspartylglucosaminidase from the venom
      of the parasitoid wasp Asobara tabida (Hymenoptera: Braconidae).
AB  - The most abundant venom protein of the parasitoid wasp Asobara tabida was
      identified to be an aspartylglucosaminidase (hereafter named AtAGA). The aim of
      the present work is the identification of: 1) its cDNA and deduced amino acid
      sequences, 2) its subunits organization and 3) its activity. The cDNA of AtAGA
      coded for a proalphabeta precursor molecule preceded by a signal peptide of 19
      amino acids. The gene products were detected specifically in the wasp venom gland
      (in which it could be found) under two forms: an (active) heterotetramer composed
      of two alpha and two beta subunits of 30 and 18 kDa respectively and a homodimer
      of 44 kDa precursor. The activity of AtAGA enzyme showed a limited tolerance
      toward variations of pH and temperatures. Since the enzyme failed to exhibit any
      glycopeptide N-glycosidase activity toward entire glycoproteins, its activity
      seemed to be restricted to the deglycosylation of free glycosylasparagines like
      human AGA, indicating AtAGA did not evolve a broader function in the course of
      evolution. The study of this enzyme may allow a better understanding of the
      functional evolution of venom enzymes in hymenopteran parasitoids.

PMID- 20036742
TI  - Dietary supplementation of alpha-linolenic acid in an enriched rapeseed oil diet
      protects from stroke.
AB  - Populations of Western countries are severely deficient in omega-3 intake, both
      in the form of alpha-linolenic acid (ALA) and the Long Chain derivatives (LC-n
      3), Eicosa-Pentaenoic-Acid and Docosa-Hexaenoic-Acid. Omega-3 insufficiency is a
      risk factor for cardiovascular and cerebral diseases such as coronary heart
      disease and stroke. Stroke is a major cause of mortality and morbidity, and
      induces a significant socioeconomic cost and a marked increase in patient/family
      burden. To date, preventive treatments and neuroprotective drugs identified in
      preclinical studies failed in clinical trials, in part because of an inability to
      tolerate drugs at neuroprotective concentrations. Therefore testing alternative
      protective strategies, such as functional foods/nutraceuticals, are of
      considerable interest. We have previously demonstrated that a single injection of
      ALA reduced ischemic damage by limiting glutamate-mediated neuronal death,
      whereas repeated injections displayed additive protective benefits as a result of
      increased neurogenesis, synaptogenesis and neurotrophin expression. Because
      intravenous injections are not a suitable long-term strategy in humans, the
      present study investigated the effect of ALA supplementation by an experimental
      diet containing rapeseed oil (RSO, a rich source of ALA) as the only source of
      lipids for stroke prevention. We tested several experimental diets which included
      5, 10, and 20% RSO-enriched diet and feeding paradigms (fresh diet was provided
      once or twice a week for 4 or 6 weeks). Our results showed that ALA supplemented
      diets are more sensitive to lipid peroxidation than a regular chow diet. Because
      the diet affected feeding behavior and animal growth, we defined concrete
      guidelines to investigate the effect of omega-3 supplementation on
      neuropathology. Among the different sets of experiments, animals fed with 10% and
      20% RSO-enriched diet displayed a reduced mortality rate, infarct size and
      increased probability of spontaneous reperfusion in the post-ischemic period. In
      addition, a drastic reduction of lipid peroxidation levels was observed in the
      ischemic brain of RSO-fed animals. Overall, our findings provide new insights
      into the potential of employing rapeseed oil as a functional food/nutraceutical
      aiding in stroke prevention and protection.

PMID- 20036743
TI  - Deciphering the function of lactococcal phage ul36 Sak domains.
AB  - Virulent phages are responsible for milk fermentation failures in the dairy
      industry, due to their ability to infect starter cultures containing strains of
      Lactococcus lactis. Single-strand annealing proteins (SSAPs) have been found in
      several lactococcal phages, among which Sak in the phage ul36. Sak has been
      recently shown to be a functional homolog of the human protein RAD52, involved in
      homologous recombination. A comparison between full-length Sak and its N- and C
      terminal domains was carried out to elucidate functional characteristics of each
      domain. We performed HPLC-SEC, AFM and SPR experiments to evaluate
      oligomerization states and compare the affinities to DNA. We have shown that the
      N-terminal domain (1-171) is essential and sufficient for oligomerization and
      binding to DNA, while the C-terminal domain (172-252) does not bind DNA nor
      oligomerize. Modelisation of Sak N-terminal domain suggests that DNA may bind a
      positively charged crevice that runs external to the ring. Annealing and
      stimulation of RecA strand exchange indicate that only the N-terminal domain is
      capable of single-strand annealing and both domains do not stimulate the RecA
      strand exchange reaction. We propose that Sak N-terminus is involved in DNA
      binding and annealing while the C-terminus may serve to contact Sak partners.

PMID- 20036744
TI  - What makes tropomyosin an actin binding protein? A perspective.
AB  - Tropomyosin is a two-chained alpha-helical coiled coil that binds along the
      length of the actin filament and regulates its function. The paper addresses the
      question of how a "simple" coiled-coil sequence encodes the information for
      binding and regulating the actin filament, its universal target. Determination of
      the tropomyosin sequence confirmed Crick's predicted heptapeptide repeat of
      hydrophobic interface residues and revealed additional features that have been
      shown to be important for its function: a 7-fold periodicity predicted to
      correspond to actin binding sites and interruptions of the canonical interface
      with destabilizing residues, such as Ala. Evidence from published work is
      summarized, leading to the proposal of a paradigm that binding of tropomyosin to
      the actin filament requires local instability as well as regions of flexibility.
      The flexibility derives from bends and local unfolding at regions with a
      destabilized coiled-coil interface, as well as from the dynamic end-to-end
      complex. The features are required for tropomyosin to assume the form of the
      helical actin filament, and to bind to actin monomers along its length. The
      requirement of instability/flexibility for binding may be generalized to the
      binding of other coiled coils to their targets.

PMID- 20036746
TI  - The role of haemocytes from the crab Carcinus aestuarii (Crustacea, Decapoda) in
      immune responses: A first survey.
AB  - For the first time, a functional study of haemocytes from the crab Carcinus
      aestuarii was performed in order to evaluate their involvement in immune
      responses. Total haemocyte count (THC), phagocytosis, haemolymph opsonisation
      properties, hydrolytic and oxidative enzyme activities, and production of
      intracellular superoxide anion were evaluated. A great variability in THC was
      recorded among individuals, and haemocyte mean number was 6.4 (x10(6)) cells/ml
      haemolymph. Although only hyalinocytes were able to phagocytose yeast cells or
      Zymosan, phagocytic index was low (3%) and did not increase significantly (4%)
      after pre-incubation of yeast and Zymosan in cell-free haemolymph, suggesting
      that haemolymph did not have opsonising properties. All haemocyte types produced
      superoxide anion, whereas only granulocytes were positive to the hydrolytic
      enzymes assayed. In addition, only granulocytes were positive to phenoloxidase
      activity. Both Petri dish and spectrophotometric assays revealed a very low
      lysozyme-like activity in cell-free haemolymph (CFH) and haemocyte lysate (HL),
      although enzyme activity was higher in CFH than in HL. Interestingly,
      normalisation of data as to total protein content in CFH and HL resulted in an
      opposite situation, lysozyme-like activity being higher in HL than in CFH. This
      demonstrated that haemolymph of C. aestuarii has a high quantity of total
      proteins, functional properties of which need to be better investigated in future
      studies. Overall, the results obtained in the present study indicated that C.
      aestuarii haemocytes are not very active phagocytic cells, but they are more
      active in terms of both hydrolytic and oxidative enzyme activities and superoxide
      anion production.

PMID- 20036745
TI  - Molecular cloning and characterization of three crustins from the Chinese white
      shrimp, Fenneropenaeus chinensis.
AB  - Antibacterial peptides crustins are the effector molecules of innate immunity in
      decapods. In this study, three crustin cDNA sequences (Fc-crus 1, Fc-crus 2, and
      Fc-crus 3) were cloned from the Chinese white shrimp Fenneropenaeus chinensis.
      The full-length cDNAs of Fc-crus 2 and 3 are 473 bp and 574 bp, respectively. The
      deduced peptides of Fc-crus 2 and 3 contain a signal peptide and a crustin domain
      at the C-terminal formed by twelve conserved cysteine residues. The partial
      sequence of Fc-cru 1 is 575 bp long and the deduced amino acids also contain a
      crustin domain. The expression profiles of these three crustins were studied with
      RT-PCR. Fc-crus 1 and Fc-crus 2 constitutively expressed in hemocytes with high
      levels, and the expression level is increased in the heart, stomach, intestine
      and ovaries when shrimp was challenged with Vibrio anguillarum, The expression of
      Fc-crus 1 and Fc-crus 2 was detected in each developmental stage. Fc-crus 3 was
      constitutively expressed in the ovaries and induced as an expression in the
      stomach. Unlike Fc-crus 1 and Fc-crus 2, the mRNA of Fc-crus 3 was not detected
      in the developmental stages extending from nauplii and mysis to post-larvae. The
      recombinant proteins containing mature Fc-crus 2 and Fc-crus 3 were recombinantly
      expressed in Escherichia coli and respectively purified. The antibacterial assays
      revealed that the recombinant mFc-crus could inhibit the growth of Gram-positive
      bacteria in vitro.

PMID- 20036747
TI  - Tissue distribution, developmental expression and up-regulation of p8 transcripts
      on stress in zebrafish.
AB  - The p8 is a transcription factor with a basic helix-loop-helix motif and a
      nuclear localization signal. A zebrafish p8 cDNA, which consists of 732 bp and
      encodes 75 amino acids, was identified in this paper. Sequence alignment showed
      that the bHLH region of p8 was well-conserved during the evolution. Phylogenetic
      analysis revealed that zebrafish p8 was close to its homologous protein in frog,
      together clustering to the clade of vertebrates. The zebrafish p8 mRNA expression
      levels varied much among the detected adult tissues, with the obvious higher
      expression in backbone and liver. During embryogenesis, the expression of
      zebrafish p8 mRNA was in higher levels in cleavage stage, decreased from blastula
      to segmentation stage, but sharply elevated at hatching stage. Quantitative real
      time PCR assay suggested up-regulation expressions of zebrafish p8 on a wide
      range of cellular stressors such as starvation, temperature, osmotic pressure and
      pH value, implying an important role of p8 gene in response to stress.

PMID- 20036748
TI  - Influence of ligand binding kinetics on functional inhibition of human
      recombinant serotonin and norepinephrine transporters.
AB  - INTRODUCTION: Monoamine reuptake inhibitors treat a wide range of CNS disorders,
      including depression, obesity, and pain. The in vitro pharmacological properties
      of these inhibitors are determined routinely using radioligand binding and/or
      neurotransmitter uptake assays. Measurements from such studies can be influenced
      by assay design and ligand-specific characteristics, both of which may contribute
      to discrepancies in literature reports. METHODS: We modified traditional
      methodologies to identify and account for factors that can confound in vitro
      potency determinations. Apparent equilibrium binding affinities (pK(i) values)
      were determined in either HEK293 cells stably-transfected with human recombinant
      serotonin (SERT) or norepinephrine (NET) transporters, or membranes prepared from
      these cell lines. Care was taken to ensure that apparent affinities were measured
      under conditions that minimized ligand depletion and established equilibrium for
      both the radioligand and the compound of interest. An unlabelled ligand kinetic
      method was used to approximate inhibitor binding kinetic constants and
      corresponding dissociation half lives. To measure inhibitory effects on substrate
      uptake, both radiolabeled neurotransmitter ([(3)H]-5-HT or [(3)H]-NE) and
      fluorescence-based assays were used. The time-dependent nature of functional
      inhibition was examined using a fluorescent substrate uptake assay which provided
      real-time measurements of NET and SERT function. RESULTS: SERT and NET inhibitors
      displayed a range of affinities, potencies, and inhibition modes by binding and
      functional uptake assays. Binding kinetic profiles for this panel of inhibitors
      were diverse, and affected in vitro measures using the former techniques.
      DISCUSSION: In the present study we describe key features of in vitro assay
      methodology that can influence the apparent pharmacological profiles of standard
      SERT and/or NET inhibitors. Such information can serve as a foundation for
      understanding the in vitro profiles of monoamine reuptake inhibitors in the
      context of their clinical efficacy and tolerability.

PMID- 20036749
TI  - The FUS3 MAPK signaling pathway of the citrus pathogen Alternaria alternata
      functions independently or cooperatively with the fungal redox-responsive AP1
      regulator for diverse developmental, physiological and pathogenic processes.
AB  - Alternaria alternata, the fungus that causes citrus brown spot, invades its hosts
      primarily through the production and action of a host-selective ACT toxin that
      kills citrus cells prior to invasion. In this study, we show that, in the
      tangerine pathotype of A. alternata, a mitogen-activated protein kinase (MAPK)
      mediated signaling pathway governs a number of biological functions, either
      separately or in a cooperative manner, with the AaAP1 gene encoding a
      transcription regulator. The reported MAPK is encoded by the AaFUS3 gene, which
      we show to be necessary for conidial development, resistance to copper
      fungicides, melanin biosynthesis, and particularly, for elaboration of the
      penetration process. In contrast, AaFUS3 negatively controls salt tolerance and
      production of several hydrolytic enzymes. AaFUS3 has no apparent role in the
      biosynthesis of host-selective toxin or in resistance to oxidative stress. Both
      AaAP1 and AaFUS3 are required for fungal resistance to 2,3,5-triiodobenzoic acid
      (TIBA), 2-chloro-5-hydroxypyridine (CHP), diethyl maleate (DEM), and many
      pyridine-containing compounds. A strain with mutations in both AaAP1 and AaFUS3
      displayed an increased sensitivity to these compounds. Expression of the AaAP1
      and AaFUS3 genes and phosphorylation of AaFUS3 were also induced by CHP, DEM, or
      TIBA. Expression of two genes coding for a putative MFS transporter was
      coordinately regulated by AaAP1 and AaFUS3. The AaAP1::sGFP (synthetic green
      fluorescent protein) fusion protein became localized in the nucleus in response
      to CHP or TIBA. Inactivation of the AaAP1 gene, however, promoted phosphorylation
      of AaFUS3. Taken together, our results indicate that A. alternata utilizes
      specialized or synergistic regulatory interactions between the AP1 and MAPK
      signaling pathways for diverse physiological functions.

PMID- 20036750
TI  - Metabolic characteristics and oxidative damage to skeletal muscle in broiler
      chickens exposed to chronic heat stress.
AB  - Emerging evidence has shown that acute heat exposure affects metabolic
      characteristics and causes oxidative damage to skeletal muscle in birds. Little
      is known, however, about such phenomena under chronic heat stress conditions. To
      address this, we designed the present study to determine the influence of cyclic
      (32 to 24 to 32 degrees C: 32 degrees C for 8 h/d, 32-24-32HS ), and constant (32
      and 34 degrees C, 32HS and 34HS, respectively) heat exposure on the metabolic and
      peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat
      stress, particularly in the 32HS and 34HS groups, depressed feed intake and
      growth, while cyclic high temperature gave rise to a less severe stress response
      in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were
      enhanced (P<0.05) by constant heat treatment; the degree of enhancement was not
      as large as the changes observed in our previous 'acute' heat stress model. The
      3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS
      (citrate synthase) enzyme activities were lowered (P<0.05) by both the cyclic and
      constant 34HS treatments, and constant 34HS group, respectively. These results
      suggest that chronic heat exposure decreases metabolic oxidation capacity in
      skeletal muscle of broiler chickens. On exposure to chronic heat stress, GPx
      activity remained relatively constant, though a temperature-dependent elevation
      in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was
      disturbed by the chronic stress condition. From these results it can be concluded
      that chronic heat stress did not induce oxidative damage to a major extent. This
      may probably be due to a decrease in metabolic oxidation capacity or due to a
      self-propagating scavenging system, though the system was not fully activated.

PMID- 20036751
TI  - Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen
      and protection from malaria, and induction of protective antibodies by sub-patent
      malaria infections, in Daraweesh.
AB  - The certainty of the protective role of acquired immunity in malaria is the major
      drive for malaria vaccine development. In this study, we measured the levels of
      total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2
      3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136
      donors from Daraweesh in Sudan. The cohort was followed for malaria infection for
      9 years. After an initial analysis, the immune response to Pf332-C231 antigen was
      the only one found associated with protection, thus taken for further analysis.
      The number of previous clinical malaria episodes experienced by the donors was
      used as an index for relative protection. The number of these episodes was found
      to be negatively correlated with the levels of pre-existing total IgG, IgG2 and
      IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195,
      p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311,
      p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by
      both patent and sub-patent infections regardless of the number of previous
      malaria episodes (1-7). Combining the correlation analysis with a multi-linear
      regression, three variable markers for protection were emerged, two age
      dependent, the antibody response to Pf332-C231 and an unidentified marker (likely
      immune response to other antigens), and the third was an age-independent
      unidentified marker (possibly gene polymorphisms). In conclusion, this report
      suggests a protective effect for IgG subclasses to Pf332-C231 antigen against
      malaria.

PMID- 20036752
TI  - Protection of BALB/c mice against Brucella melitensis 16 M infection induced by
      vaccination with live Escherchia coli expression Brucella P39 protein.
AB  - The periplasmic binding protein (P39) antigen of Brucella melitensis 16 M was
      previously identified as Th1 dominant antigens. In this study, the potential for
      this antigen to function as vaccine against B. melitensis 16 M infection in
      BALB/c mice has been analyzed, and the humoral and cellular immune responses
      induced have been also characterized. Mice were injected intraperitoneally with
      live Escherichia coli alone or with that which express Brucella P39, two times at
      4 weeks intervals. The live E. coli BL21 (DE3) pEt15b-p39 vaccine elicited a T
      cell-proliferative response and also induced a gamma interferon production upon
      re-stimulation with either the bacterial extract or P39 as a specific antigen.
      Also the live E. coli BL21 (DE3) pEt15b-p39 vaccine has been found to induce a
      strong humoral response (IgG1 and IgG2a). Compared to the saline-inoculated
      control, vaccination of mice with E. coli BL21pEt15b-p39 at 3 weeks prior to the
      challenge infection, significantly reduced the number of strain 16 M bacteria in
      spleens at 4 and 8 weeks post-challenge infection in all vaccinated mice
      (p<0.001).

PMID- 20036755
TI  - Use of biomarkers in the discovery of novel anti-schizophrenia drugs.
AB  - Schizophrenia is characterized by a diverse symptomatology that often includes
      positive, cognitive and negative symptoms. Current anti-schizophrenic drugs act
      at multiple receptors, but little is known about how each of these receptors
      contributes to their mechanisms of action. Screening of novel anti-schizophrenic
      drug candidates targeting single receptors will be based on biomarker assays that
      measure signalling pathways, transcriptional factors, epigenetic mechanisms and
      synaptic function and translate these effects to behavioural effects in animals
      and humans. This review discusses current states of the validity of biomarkers in
      the identification of novel anti-schizophrenic drug candidates.

PMID- 20036753
TI  - Infection of less virulent Helicobacter pylori strains in asymptomatic healthy
      individuals in Thailand as a potential contributing factor to the Asian enigma.
AB  - In Thailand, gastric cancer incidence is considerably low despite the high
      prevalence of Helicobacter pylori infection. We investigated the prevalence of H.
      pylori infection and the genotypes of cagA by using 179 stool specimens obtained
      from asymptomatic Thai individuals. In this study, the prevalence of H. pylori
      infection was 43.6%, and the detection rate of cagA-positive strains was 43.5%.
      In addition, the proportion of the highly virulent East-Asian type of cagA was
      7.2%. These results indicate that the low prevalence of cagA-positive H. pylori
      strain as well as the low prevalence of East-Asian genotype cagA-positive strains
      may contribute to the low gastric cancer incidence.

PMID- 20036756
TI  - Assessment of the potential mutagenicity of organochlorine pesticides (OCPs) in
      contaminated sediments from Taihu Lake, China.
AB  - The residual levels and mutagenic potency of OCPs were studied in surface
      sediments collected from Taihu Lake, China. The concentrations of OCPs detected
      in surface sediments revealed a wide range of fluctuation from 4.22 to 461ng/g
      dry weight (dw). Among the individual components of OCPs, much higher
      coefficients of variance (0.38-1.57) for each compound were detected, indicating
      significant difference of OCP residues among different areas over the lake.
      Mutagenicity of the crude extractable organic matter (EOM) from surface sediments
      in six typical regions was performed with Salmonella/microsome tests (Salmonella
      strains TA98 and TA100 with/without metabolic activation S9 mix). TA98 was more
      sensitive and the main mutagens detected were frameshift toxicants. Sediments
      collected from the north-west showed higher potency to induce mutagenicity than
      other regions. Poor correlation between OCP concentrations and mutagenicity
      suggested OCPs were not responsible for the detected mutagenic effects in
      sediments. Combining chemical analysis with bioassays will be a novel and useful
      tool for finding out the responsible environmental mutagens.

PMID- 20036757
TI  - The role of colonoscopy and radiological procedures in the management of acute
      lower intestinal bleeding.
AB  - There are multiple strategies for evaluating and treating lower intestinal
      bleeding (LIB). Colonoscopy has become the preferred initial test for most
      patients with LIB because of its diagnostic and therapeutic capabilities and its
      safety. However, few studies have directly compared colonoscopy with other
      techniques and there are controversies regarding the optimal timing of
      colonoscopy, the importance of colon preparation, the prevalence of stigmata of
      hemorrhage, and the efficacy of endoscopic hemostasis. Angiography, radionuclide
      scintigraphy, and multidetector computed tomography scanning are complementary
      modalities, but the requirement of active bleeding at the time of the examination
      limits their routine use. In addition, angiography can result in serious
      complications. This review summarizes the available evidence regarding
      colonoscopy and radiographic studies in the management of acute LIB.

PMID- 20036758
TI  - Electronic image of the month. Cardiac dysphagia.

PMID- 20036759
TI  - Terminology of World War II and medicine.

PMID- 20036760
TI  - Refractory lymphocytic enterocolitis and tumor necrosis factor antagonist
      therapy.
AB  - BACKGROUND & AIMS: Lymphocytic enterocolitis is a malabsorptive syndrome
      characterized by severe small-bowel villous abnormality and crypt hyperplasia and
      dense infiltrate of lymphocytes throughout the gastrointestinal tract. METHODS:
      We present 2 patients with lymphocytic enterocolitis refractory to usual medical
      therapy who were treated with tumor necrosis factor antagonists. RESULTS: Both
      patients had clinical improvement in diarrheal symptoms and intestinal histologic
      abnormalities. CONCLUSIONS: Tumor necrosis factor-alpha antagonists such as
      infliximab or adalimumab may be a new treatment option for patients with severe
      refractory lymphocytic enterocolitis not responding to corticosteroids.

PMID- 20036761
TI  - Factors that predict outcome of abdominal operations in patients with advanced
      cirrhosis.
AB  - BACKGROUND & AIMS: Patients with cirrhosis have an increased risk of
      complications during surgery that is relative to the severity of liver disease;
      it is a challenge to determine which patients are the best candidates for
      surgery. We performed a hospital-based study to identify factors that might
      facilitate selection of operative candidates and guide their management. METHODS:
      A retrospective review was performed of 100 cirrhotic patients (50 classified as
      Child-Turcotte-Pugh [CTP] A, 33 as CTP B, and 17 as CTP C) who underwent
      abdominal surgery at an institution specializing in liver medicine and transplant
      from 2002-2008. Significant univariate variables were evaluated by multivariate
      logistic regression models to identify factors that correlate with outcome.
      RESULTS: The overall, 30-day postoperative mortality rate was 7%. The mortality
      for patients who were CTP A was 2%, CTP B was 12%, and CTP C was 12%; 33 patients
      had a Model for End-Stage Liver Disease (MELD) score >or=15, with 29% mortality.
      On the basis of multivariate analyses, risk factors for adverse outcome were
      American Society of Anesthesiologists (ASA) score >3; procedures being emergent;
      intraoperative blood transfusion; intraoperative blood loss >150 mL; presence of
      ascites; total bilirubin level >1.5 mg/dL; and albumin level <3 mg/dL. Addition
      of serum albumin to MELD score showed that patients with MELD score >or=15 and
      albumin <or=2.5 mg/dL (vs >2.5 mg/dL) had significantly increased mortality (60%
      vs 14%, P < .01) and independently increased probability of adverse outcome (odds
      ratio, 8.4; P = .015). CONCLUSIONS: For patients with MELD scores >or=15, the
      preoperative albumin level correlates with outcome and could guide operative
      decisions. Intraoperative packed red blood cell transfusion correlates with
      adverse outcome and should be limited.

PMID- 20036762
TI  - Danish patients with chronic pancreatitis have a four-fold higher mortality rate
      than the Danish population.
AB  - BACKGROUND & AIMS: We investigated mortality of patients with chronic
      pancreatitis (CP), compared with the Danish population and sought to determine
      whether clinical presentations of CP can be used in prognosis. We also
      investigated clinical factors associated with mortality and causes of death among
      these patients. METHODS: The Copenhagen Pancreatitis Study is a prospective study
      of patients admitted from 1977 to 1982 to the 5 main hospitals in Copenhagen with
      a diagnosis of acute pancreatitis or CP. In 2008, follow-up data were collected
      from these patients from the Danish Registries; this subcohort comprised 290
      patients with probable (n = 41) or definite CP (n = 249). RESULTS: The mortality
      of patients with definite CP was 4-fold that of the Danish population and
      significantly higher than that of patients with probable CP (P = .003; 95%
      confidence interval [CI], 1.21-2.57); patients with probable CP had a 2- to 3
      fold higher mortality rate than the population. In patients with definite CP,
      factors significantly associated with mortality included non-employment (P =
      .015; 95% CI, 0.53-0.93), and being underweight (P = .020; 95% CI, 0.52-0.95).
      Sex, alcohol use, smoking, single versus co-living, exocrine insufficiency,
      diabetes, pancreatic calcification, CP inheritance, painless CP, acute
      exacerbation of CP, or surgery for CP had no impact on survival. The most
      frequent causes of death were digestive diseases (19.5%), malignancies (19.5%),
      and cardiovascular diseases (11.3%). CONCLUSIONS: Danish patients with definite
      CP had a 4-fold higher mortality rate compared with the background population and
      a higher mortality rate than patients with probable CP. Being nonemployed or
      underweight had significant impact on survival.

PMID- 20036764
TI  - Structure and function of yeast glutaredoxin 2 depend on postranslational
      processing and are related to subcellular distribution.
AB  - We have previously shown that glutaredoxin 2 (Grx2) from Saccharomyces cerevisiae
      localizes at 3 different subcellular compartments, cytosol, mitochondrial matrix
      and outer membrane, as the result of different postranslational processing of one
      single gene. Having set the mechanism responsible for this remarkable phenomenon,
      we have now aimed at defining whether this diversity of subcellular localizations
      correlates with differences in structure and function of the Grx2 isoforms. We
      have determined the N-terminal sequence of the soluble mitochondrial matrix Grx2
      by mass spectrometry and have determined the exact cleavage site by Mitochondrial
      Processing Peptidase (MPP). As a consequence of this cleavage, the mitochondrial
      matrix Grx2 isoform possesses a basic tetrapeptide extension at the N-terminus
      compared to the cytosolic form. A functional relationship to this structural
      difference is that mitochondrial Grx2 displays a markedly higher activity in the
      catalysis of GSSG reduction by the mitochondrial dithiol dihydrolipoamide. We
      have prepared Grx2 mutants affected on key residues inside the presequence to
      direct the protein to one single cellular compartment; either the cytosol, the
      mitochondrial membrane or the matrix and have analyzed their functional
      phenotypes. Strains expressing Grx2 only in the cytosol are equally sensitive to
      H(2)O(2) as strains lacking the gene, whereas those expressing Grx2 exclusively
      in the mitochondrial matrix are more resistant. Mutations on key basic residues
      drastically affect the cellular fate of the protein, showing that evolutionary
      diversification of Grx2 structural and functional properties are strictly
      dependent on the sequence of the targeting signal peptide.

PMID- 20036765
TI  - Synthesis, characterization and ab initio simulation of magnesium-substituted
      hydroxyapatite.
AB  - The substitution of magnesium in hydroxyapatite (HA) was examined in HA nano
      crystals synthesized by the wet-chemical precipitation method at 90 degrees C.
      Comprehensive characterization techniques, including X-ray diffraction, X-ray
      fluorescence, field emission scanning electron microscopy, high-resolution
      transmission electron microscopy, thermogravimetric analysis and Rietveld
      refinement, provided experimental evidence of the effects of Mg substitution on
      the phase, crystallinity, chemical composition, crystal size, morphology, thermal
      stability and crystal lattice structure of HA. A computational study using ab
      initio generalized gradient approximation density functional theory was performed
      to reveal changes in lattice parameters and preferential calcium sites for Mg
      substitution in HA. The experimental results showed that a limited amount of Mg
      (Mg/(Mg+Ca) between 5 and 7 mol.%) could successfully substitute for Ca in HA. HA
      crystallites became smaller and more irregular, and they formed greater
      agglomerates with Mg substitution. Mg substitution resulted in decreases in the
      crystallinity and thermal stability of HA. The lattice constants, a and c,
      decreased with increasing Mg substitution. The simulation results revealed that
      the Ca(1) sites in HA lattices were energetically favored sites for Mg
      substitution.

PMID- 20036763
TI  - Differential expression of respiratory long-term facilitation among inbred rat
      strains.
AB  - We tested the hypotheses that: (1) long-term facilitation (LTF) following acute
      intermittent hypoxia (AIH) varies among three inbred rat strains: Fischer 344
      (F344), Brown Norway (BN) and Lewis rats and (2) ventral cervical spinal levels
      of genes important for phrenic LTF (pLTF) vary in association with pLTF
      magnitude. Lewis and F344, but not BN rats exhibited significant increases in
      phrenic and hypoglossal burst amplitude 60min post-AIH that were significantly
      greater than control experiments without AIH, indicating strain differences in
      phrenic (98%, 56% and 20%, respectively) and hypoglossal LTF (66%, 77% and 5%,
      respectively). Ventral spinal 5-HT(2A) receptor mRNA and protein levels were
      higher in F344 and Lewis versus BN, suggesting that higher 5-HT(2A) receptor
      levels are associated with greater pLTF. More complex relationships were found
      for 5-HT(7), BDNF and TrkB mRNA. BN had higher 5-HT(7) and TrkB mRNA versus F344;
      BN and Lewis had higher BDNF mRNA levels versus F344. Genetic variations in
      serotonergic function may underlie strain differences in AIH-induced pLTF.

PMID- 20036766
TI  - In vitro cytotoxicity of porous silicon microparticles: effect of the particle
      concentration, surface chemistry and size.
AB  - We report here the in vitro cytotoxicity of mesoporous silicon (PSi)
      microparticles on the Caco-2 cells as a function of particle size fractions (1.2
      75 microm), particle concentration (0.2-4 mg ml(-1)) and incubation times (3, 11
      and 24 h). The particle size (smaller PSi particles showed higher cytotoxicity)
      and the surface chemistry treatment of the PSi microparticles were considered to
      be the key factors regarding the toxicity aspects. These effects were significant
      after the 11 and 24 h exposure times, and were explained by cell-particle
      interactions involving mitochondrial disruption resulting from ATP depletion and
      reactive oxygen species production induced by the PSi surface. These events
      further induced an increase in cell apoptosis and consequent cell damage and cell
      death in a dose-dependent manner and as a function of the PSi particle size.
      These effects were, however, less pronounced with thermally oxidized PSi
      particles. Under the experimental conditions tested and at particle sizes >25
      microm, the non-toxic threshold concentration for thermally hydrocarbonized and
      carbonized PSi particles was <2 mg ml(-1), and for thermally oxidized PSi
      microparticles was <4 mg ml(-1).

PMID- 20036767
TI  - Novel fructopyranose oligosaccharides isolated from fermented beverage of plant
      extract.
AB  - Four oligosaccharides containing a fructopyranosyl residue have been found from
      fermented beverage of plant extract and isolated from the beverage using carbon
      Celite column chromatography and preparative high performance liquid
      chromatography. Structure confirmation of the saccharides was provided by
      methylation analysis, MALDI-TOF-MS and NMR measurements. These saccharides were
      identified as oligosaccharides of fructopyranoside series; beta-D-fructopyranosyl
      (2-->6)-D-fructofuranose (1), beta-D-fructopyranosyl-(2-->1)-D-fructopyranose
      (2), beta-D-fructopyranosyl-(2-->1)-beta-D-fructofuranosyl-(2<-->1)-alpha-D
      glucopyranoside (3), and beta-D-fructopyranosyl-(2-->6)-alpha-D-glucopyranosyl
      (1<-->2)-beta-D-fructofuranoside (4). Saccharides 3 and 4 among novel saccharides
      1, 3, and 4 were named 'pyrano-1-kestose (pyrano-isokestose)' and 'pyrano
      neokestose', respectively.

PMID- 20036768
TI  - Search for evidence of life in space: analysis of enantiomeric organic molecules
      by N,N-dimethylformamide dimethylacetal derivative dependant Gas Chromatography
      Mass Spectrometry.
AB  - Within the context of the future space missions to Mars (MSL 2011 and Exomars
      2016), which aim at searching for traces of life at the surface, the detection
      and quantitation of enantiomeric organic molecules is of major importance. In
      this work, we have developed and optimized a method to derivatize and analyze
      chiral organic molecules suitable for space experiments, using N,N
      dimethylformamide dimethylacetal (DMF-DMA) as the derivatization agent. The
      temperature, duration of the derivatization reaction, and chromatographic
      separation parameters have been optimized to meet instrument design constraints
      imposed upon space experiment devices. This work demonstrates that, in addition
      to its intrinsic qualities, such as production of light-weight derivatives and a
      great resistance to drastic operating conditions, DMF-DMA facilitates simple and
      fast derivatization of organic compounds (three minutes at 140 degrees C in a
      single-step) that is suitable for an in situ analysis in space. By using DMF-DMA
      as the derivatization agent, we have successfully identified 19 of the 20
      proteinic amino acids and been able to enantiomerically separate ten of the
      potential 19 (glycine being non-chiral). Additionally, we have minimized the
      percentage of racemized amino acid compounds produced by optimizing the
      conditions of the derivatization reaction itself. Quantitative linearity studies
      and the determination of the limit of detection show that the proposed method is
      also suitable for the quantitative determination of both enantiomeric forms of
      most of the tested amino acids, as limits of detection obtained are lower than
      the ppb level of organic molecules already detected in Martian meteorites.

PMID- 20036769
TI  - Dual parallel mass spectrometry for lipid and vitamin D analysis.
AB  - There are numerous options for mass spectrometric analysis of lipids, including
      different types of ionization, and a wide variety of experiments using different
      scan modes that can be conducted. Atmospheric pressure chemical ionization (APCI)
      and electrospray ionization (ESI) provide complementary types of information that
      are both desirable. However, the duty cycle of the mass spectrometer places
      limits on the number of experiments that can be performed, and instruments
      usually employ only one type of ionization at a time. This work describes the
      approaches we have used that employ two mass spectrometers in parallel or in a
      column-switching configuration that allows multiple ionization modes and types of
      experiments to be conducted simultaneously during a single chromatographic run.
      These data demonstrate how use of two systems can reduce or eliminate the need
      for repeat injections and repetitive experiments. Approaches are described that
      employ two mass spectrometers connected in parallel as detectors for a single
      chromatographic system (LC1/MS2) or that employ two liquid chromatographs and two
      mass spectrometers in a column-switching arrangement (LC2/MS2). Examples of
      LC1/MS2 analyses of triacylglycerols (TAGs), sphingolipids, and vitamin D are
      given, as well as an example of an LC2/MS2 experiment that is used to perform
      analysis of both polar and non-polar lipids in a total lipid extract.

PMID- 20036770
TI  - Dual-cloud point extraction and tertiary amine labeling for selective and
      sensitive capillary electrophoresis-electrochemiluminescent detection of auxins.
AB  - The low concentrations of the auxins in samples of plant tissue necessitate the
      use of selective and sensitive techniques for their quantification. Herein a
      selective and sensitive method based on dual-cloud point extraction (dCPE) and
      tertiary amine labeling for the quantification of indole-3-acetic acid (IAA) and
      indole-3-butyric acid (IBA) by capillary electrophoresis-electrochemiluminescence
      (CE-ECL) is proposed. The procedure for dCPE included two cloud point processes
      with Triton X-114 as the extractant. The two auxins became hydrophobic in an
      acidic solution and were extracted into surfactant-rich phase after the first
      cloud point procedure. They were then back-extracted into the alkaline aqueous
      phase during the second cloud point step. The extracted auxins were reacted with
      2-(2-aminoethyl)-1-methylpyrrolidine (AEMP) in acetonitrile that contained N,N'
      dicyclohexylcarbodiimide and 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine to
      produce their AEMP-derivatives. The two auxin-AEMP-derivatives were subjected
      into CE and detected by Ru(bpy)(3)(2+)-based ECL. The preconcentration factors
      for IAA and IBA with dCPE were 40.5 and 43.4, respectively. The on-capillary
      detection limits (S/N=3) were 2.5 and 2.8nM for IAA and IBA. This protocol
      presents a clear advantage in that it reduces the interference from the matrixes
      extensively and gives a high sensitivity for the detection of auxins. The
      proposed method was applied successfully to the detection of the two auxins in
      acacia tender leaves, buds, and bean sprout.

PMID- 20036771
TI  - A rapid method for simultaneous determination of 14 phenolic compounds in Radix
      Puerariae using microwave-assisted extraction and ultra high performance liquid
      chromatography coupled with diode array detection and time-of-flight mass
      spectrometry.
AB  - A microwave-assisted extraction (MAE) and ultra high performance liquid
      chromatography coupled with diode array detection and time-of-flight mass
      spectrometry (UHPLC-DAD-TOF-MS) method was developed for simultaneous
      determination of 14 phenolic compounds in the root of Pueraria lobata (Wild.)
      Ohwi and Pueraria thomsonii Benth. Operational conditions of MAE were optimized
      by central composite design (CCD). The optimized result was 65% ethanol as
      extraction solvent, 17mL of extraction volume, 100 degrees C of extraction
      temperature and 2min of hold time. A Zorbax SB C(18) (50mmx4.6mm I.D., 1.8microm)
      and gradient elution were used during the analysis. The chromatographic peaks of
      14 investigated compounds in samples were successfully identified by comparing
      their retention time, UV spectra and TOF mass data with the reference substances.
      All calibration curves showed good linearity (r>0.9997) within the test ranges.
      The intra-day and inter-day variations were less than 1.77% and 2.88%,
      respectively. The developed method was successfully applied to determine the
      investigated compounds in 10 samples of Radix Puerariae Lobatae and Radix
      Puerariae Thomsonii, respectively. The result indicated that MAE and UHPLC-DAD
      TOF-MS system might provide a rapid method for the quality control of Radix
      Puerariae.

PMID- 20036772
TI  - Determination of atracurium, cisatracurium and mivacurium with their impurities
      in pharmaceutical preparations by liquid chromatography with charged aerosol
      detection.
AB  - The Corona CAD (charged aerosol detection) is a new type of detector introduced
      for LC applications that has recently become widely applied in pharmaceutical
      analysis. The Corona CAD measures a physical property of analyte and responds to
      almost all non-volatile species, independently of their nature and spectral or
      physicochemical properties. The LC method with charged aerosol detection was
      developed for the determination of three isomers of atracurium, cisatracurium and
      also three isomers of mivacurium with their impurities. The limit of quantitation
      for laudanosine was 1 microg ml(-1). The elaborate method for the analysis of
      those active substances and laudanosine proved to be fast, precise, accurate and
      sensitive. All other impurities were identified using time-of-flight mass
      spectrometry with electrospray ionization.

PMID- 20036774
TI  - Calcium dyshomeostasis in white matter pathology.
AB  - Calcium (Ca2+) dyshomeostasis is a major event in the pathophysiology of white
      matter disorders of the brain and spinal cord. All cellular components of white
      matter, including macroglial cells and axons, are endowed with membrane Ca2+
      permeable receptors and channels lodged in the cell membrane, as well as store
      operated channels and pumps. Intracellular Ca2+ overload resulting from
      deregulated activity of channels, such as those opened by glutamate and ATP, is
      deleterious to glia and axons. In this review, I summarize recent advances in our
      understanding of white matter Ca2+ dyshomeostasis in experimental paradigms which
      are relevant to stroke, perinatal ischemia, multiple sclerosis, psychiatric
      disorders, Alzheimer's disease and traumatic injury, and discuss some of the
      clinical implications of these findings.

PMID- 20036773
TI  - Expression of folate transporters in human placenta and implications for
      homocysteine metabolism.
AB  - Poor folate status during pregnancy can lead to elevated maternal plasma levels
      of homocysteine (Hcy) with associated pregnancy complications and adverse
      neonatal outcomes, suggesting placental metabolism of Hcy might be an important
      determinant in influencing fetal development. The metabolic pathways for Hcy in
      placenta are not well defined. In this study we examined the gene expression of
      key enzymes involved in Hcy metabolism in first trimester and term human placenta
      to determine which metabolic pathways prevail. Expression of mRNA for methionine
      synthase and 5,10-methylene tetrahydrofolate reductase, enzymes involved in the
      methionine cycle and responsible for the re-methylation of Hcy to methionine,
      were expressed at similar levels between first trimester and term and in
      comparison to human liver as positive control. In contrast, cystathionine beta
      synthase mRNA expression was markedly lower than that in liver at both
      gestational periods. Betaine-homocysteine methyltransferase mRNA was undetectable
      at either gestational age. These data suggest that re-methylation of Hcy using
      methyl donation from 5-methyltetrahydrofolate is the prevalent pathway,
      indicating a marked reliance on folate availability. This led to further
      investigations examining the expression and localisation of folate transporters
      in first trimester and term placenta. Folate receptor alpha (FRalpha) was highly
      polarised to the microvillous plasma membrane (MVM) of the syncytiotrophoblast at
      both gestational periods, a distribution shared by the proton-coupled folate
      transporter which co-localised with FRalpha. Reduced folate carrier was
      distributed to both MVM and basal syncytiotrophoblast plasma membranes at term
      suggesting a role at both loci, and in first trimester was localised to MVM as
      well as cytotrophoblast plasma membranes. These data support the concept that
      placental folate transport is established early in pregnancy, providing folate
      for utilisation in placental Hcy metabolism.

PMID- 20036775
TI  - Replacement of Imu-Cmu intron by NeoR gene alters Imu germ-line expression but
      has no effect on V(D)J recombination.
AB  - The NeoR gene has often been used to unravel the mechanisms underlying long-range
      interactions between promoters and enhancers during V(D)J assembly and class
      switch recombination (CSR) in the immunoglobulin heavy chain (IgH) locus. This
      approach led to the notion that CSR is regulated through competition of germ-line
      (GL) promoters for activities displayed by the 3' regulatory region (3'RR). This
      polarized long-range effect of the 3'RR is disturbed upon insertion of NeoR gene
      in the IgH constant (C(H)) region, where only GL transcription derived from
      upstream GL promoters is impaired. In the context of V(D)J recombination,
      replacement of Emu enhancer or Emu core enhancer (cEmu) by NeoR gene fully
      blocked V(D)J recombination and mu0 GL transcription which originates 5' of DQ52
      and severely diminished Imu GL transcription derived from Emu/Imu promoter,
      suggesting a critical role for cEmu in the regulation of V(D)J recombination and
      of mu0 and Imu expression. Here we focus on the effect of NeoR gene on mu0 and
      Imu GL transcription in a mouse line in which the Imu-Cmu intron was replaced by
      a NeoR gene in the sense-orientation. B cell development was characterized by a
      marked but incomplete block at the pro-B cell stage. However, V(D)J recombination
      was unaffected in sorted pro-B and pre-B cells excluding an interference with the
      accessibility control function of Emu. mu0 GL transcription initiation was
      relatively normal but the maturation step seemed to be affected most likely
      through premature termination at NeoR polyadenylation sites. In contrast, Imu
      transcription initiation was impaired suggesting an interference of NeoR gene
      with the IgH enhancers that control Imu expression. Surprisingly, in stark
      contrast with the NeoR effect in the C(H) region, LPS-induced NeoR expression
      restored Imu transcript levels to normal. The data suggest that Emu enhancer may
      be the master control element that counteracts the down-regulatory "Neo effect"
      on Imu expression upon LPS stimulation. More importantly, they reveal a complex
      and developmentally regulated interplay between IgH enhancers in the control of
      Imu expression.

PMID- 20036776
TI  - Does the message matter? The effect of song type on infants' pitch preferences
      for lullabies and playsongs.
AB  - Preverbal infants are attuned to the different emotional messages contained in
      playsongs and lullabies. However, it is unclear which performance properties of
      singing underlie infants' perception of the communicative intent of infant
      directed singing. Volkova, Trehub, and Schellenberg (2006) recently demonstrated
      that 6- and 7-month-old infants preferred low-pitched to high-pitched renditions
      of lullabies, suggesting that pitch may be one performance characteristic that
      conveys the communicative intent in infant-directed singing. In the current
      study, we evaluated 6- and 7-month-old infants' natural preferences for
      unfamiliar, expressive lullabies and playsongs as a function of pitch using a
      head-turn preference procedure. Infants preferred low-pitched over high-pitched
      versions of lullabies and high-pitched over low-pitched versions of playsongs.
      Results suggest that the overall pitch of a song is communicative to infants and
      that the affective nature of music can have an effect on infants' pitch
      preferences. That is, infants' preferences for pitch are context-dependent.

PMID- 20036777
TI  - Exploratory factor analysis of human infant temperament in the rhesus monkey.
AB  - The triadic model of human infant temperament, involving Negative Affectivity,
      Orienting/Regulation, and Surgency/Extraversion factors, was applied to the
      rhesus neonate using exploratory factor analysis (EFA). Replicating and expanding
      earlier work in rhesus monkeys, the three-factor solution produced latent
      constructs comparable to human neonatal temperament.

PMID- 20036778
TI  - Behavioral development of infant holding and its laterality in relation to
      mothers' handedness and child-care attitude.
AB  - The holding of 465 Japanese infants by their mothers was longitudinally observed
      at 4 and 9 months with several checkups and questionnaires of physical and
      psychological development and child-care attitude in a larger longitudinal study
      of mother-child relationships. A left side bias in holding was significant for
      the 4-month-old infants. The infants' increased autonomy in their ability to
      adopt a posture at 9 months weakened the holding bias. The mothers' handedness
      was related to different right/left hand contact patterns, but it was significant
      only for holding on the left side. The infants' reflexes relating to posture did
      not correlate with the holding bias at 4 months. The meaning and possible
      determinants of holding laterality are discussed.

PMID- 20036779
TI  - The a2 isoform of vacuolar ATPase is a modulator of implantation and feto
      maternal immune tolerance in early pregnancy.
AB  - In mammalian reproduction, two immunologically disparate entities, the mother and
      her fetus, co-exist in close proximity and mutually tolerate each other. The
      maternal immune system plays a major contributing role in the reproductive
      outcome. A coordinated set of immunological events takes place between the
      maternal and fetal cells to ensure fetal survival. Among these, cytokines
      secreted by proximal maternal immune cells as well as fetal trophoblast cells
      play a major role in feto-maternal tolerance. In this review, we describe the
      role of the vacuolar ATPase (and more specifically the a2 isoform, a2V-ATPase) in
      controlling the expression of these vital cytokines. a2V-ATPase is a key enzyme
      that controls the acidification of intracellular vesicles and the extracellular
      environment, processes that play a major role in cellular function. The
      localization of a2V-ATPase in tissues and immune cells of the reproductive tract
      which are essential for pregnancy will be described. Information will be provided
      on the role of a2V-ATPase on aspects of cell development in pregnancy, from
      fertilization to implantation and fetal growth. Particular emphasis will be
      placed on the role of a2V-ATPase in (a) regulating parts of the cytokine network
      at the implantation site and (b) attenuating the potentially harmful maternal
      immune response against trophoblast cells.

PMID- 20036780
TI  - Reciprocal enhancement of uptake and toxicity of cadmium and calcium in rainbow
      trout (Oncorhynchus mykiss) liver mitochondria.
AB  - The interactive effects of cadmium (Cd) and calcium (Ca) on energy metabolism in
      rainbow trout liver mitochondria were studied to test the prediction that Ca
      would protect against Cd-induced mitochondrial liability. Isolated rainbow trout
      liver mitochondria were energized with malate and glutamate and exposed to
      increasing concentrations (5-100 microM) of Cd and Ca singly and in combination
      at 15 degrees C. Accumulation of Cd and Ca in the mitochondria and mitochondrial
      respiration (oxygen consumption) rates were measured. Additionally, un-energized
      mitochondria were incubated with low doses (1 microM) of Cd and Ca singly and in
      combination, with time-course measurements of cation accumulation/binding and
      oxygen consumption rates. In energized actively phosphorylating mitochondria, the
      uptake rates of both Cd and Ca were dose-dependent and enhanced when administered
      concurrently. Upon low-dose incubation, Cd accumulation was rapid and peaked in 5
      min, while no appreciable uptake of Ca occurred. Functionally, the resting (state
      4, ADP-limited) respiration rate was not affected in the dose-response exposure,
      but it decreased remarkably on low-dose incubation. Adenosine diphosphate (ADP)
      stimulated respiration (state 3) rate was impaired dose-dependently with maximal
      inhibitions (at the highest dose, 100 microM) of 32, 64 and 73% for Ca, Cd, and
      combined exposures, respectively. The combined effects of Ca and Cd suggested
      synergistic (more than additive) action and partial additivity of effects at low
      and higher doses of the two cations, respectively. Moreover, on a molar basis, Cd
      was twice as toxic as Ca to rainbow trout liver mitochondria and when combined,
      approximately 90% of the effects were attributable to Cd. The coupling
      efficiency, as measured by respiratory control ratio (RCR) and phosphorylation
      efficiency, measured as ADP/O ratio, both decreased as the exposure dosage and
      duration increased. In addition, Cd and Ca exposure decreased mitochondrial
      proton leak (state 4+ respiration) rates on prolonged exposure possibly by
      inhibiting processes that generate mitochondrial membrane potential, the force
      that drives proton leak. Overall these data suggest that the widely accepted
      theme that Ca and Cd are competitive antagonists does not hold for mitochondrial
      effects and that Cd and Ca cooperate to impair oxidative phosphorylation in
      rainbow trout liver mitochondria.

PMID- 20036781
TI  - [Atypical unilateral glaucoma in a young patient].
AB  - BACKGROUND: Diagnostic and therapeutic problems are common in cases of unilateral
      optical neuropathy with elevated intraocular pressure (IOP) CASE REPORT: A 17
      year-old boy was referred for visual acuity loss and elevated IOP at 40mmHg in
      his left eye. Juvenile open-angle glaucoma (JOAG) was diagnosed based on the
      clinical and paraclinical examinations. In spite of a maximal hypotensive
      treatment, tensional control was insufficient and a filtering surgery procedure
      was necessary. IOP control was good 6 months after surgery, but functional and
      anatomical analysis showed neuropathic progression and a bilateralization of the
      disease. CONCLUSION: The diagnosis of JOAG is difficult and sometimes delayed.
      Secondary bilateralization commonly causes diagnostic problems which can delay
      specific and appropriate management. Systematic screening should be performed
      during infancy when a strong family history of glaucoma is known.

PMID- 20036782
TI  - Impacts of changes in water quality on recreation behavior and benefits in
      Finland.
AB  - The implementation of the European Union Water Framework Directive (WFD) requires
      nationally generalizable estimates of the benefits of protecting inland and
      coastal waters. As an alternative to benefit transfers and meta-analyses, we
      utilize national recreation inventory data combined with water quality data to
      model recreation participation and estimate the benefits of water quality
      improvements. Using hurdle models, we analyze the association of water clarity in
      individuals' home municipalities with the three most common water recreation
      activities--swimming, fishing and boating. The results show no effect on boating,
      but improved water clarity would increase the frequency of close-to-home swimming
      and fishing, as well as the number of fishers. Furthermore, to value the
      potential benefits of the WFD, we estimate the consumer surplus of a water
      recreation day using a travel cost approach. A water policy scenario with a 1-m
      improvement in water clarity for both inland and coastal waters indicates that
      the consumer surplus would increase 6% for swimmers and 15% for fishers. In
      contrast to previously estimated abatement costs to improve water quality, net
      benefits could turn out to be positive. Our study is a promising example of
      applying existing national recreation inventory data to estimate the benefits of
      water quality improvements for the purposes of the WFD.

PMID- 20036783
TI  - A comparison of the frequencies of medical therapies for overactive bladder in
      men and women: analysis of more than 7.2 million aging patients.
AB  - BACKGROUND: The study of overactive bladder (OAB) symptoms has historically
      focused on women. However, it is now evident that men, including those with
      benign prostatic hyperplasia, have OAB symptoms that respond to anticholinergic
      therapy. The current OAB treatment frequencies by gender are unknown. OBJECTIVE:
      The aim of the study was to compare the treatment patterns among men and women
      diagnosed with OAB. DESIGN, SETTING, AND PARTICIPANTS: Patients >=45 yr in the
      IMS Health data set with more than one diagnosis code for OAB during a 12-mo
      period ending December 2007. INTERVENTION: Treated patients filled a prescription
      for either an anticholinergic or a tricyclic antidepressant medication; untreated
      patients did not. MEASUREMENTS: Frequencies of OAB diagnoses and medical
      therapies by age and gender were compared. RESULTS AND LIMITATIONS: Of the
      7,244,501 patients >=45yr with an OAB diagnosis, 24.4% of these were treated;
      75.6% went untreated. Only 25.6% of those treated were men. The diagnosis and
      treatment frequency increased in both men and women as a function of age.
      However, in every age group, there was a significantly (p<0.001) decreased
      proportion of men treated compared with women. CONCLUSIONS: Despite OAB
      prevalence, many patients receive no medical treatment. Although the usefulness
      of OAB medications in men is becoming increasingly recognized, men are
      significantly less likely to be treated with OAB medications than women.

PMID- 20036784
TI  - Downsides of robot-assisted laparoscopic radical prostatectomy: limitations and
      complications.
AB  - CONTEXT: Robot-assisted laparoscopic radical prostatectomy (RALP) using the da
      Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in
      widespread use for the management of localised prostate cancer (PCa). Many
      reports of the safety and efficacy of this procedure have been published.
      However, there are few specific reports of the limitations and complications of
      RALP. OBJECTIVE: The primary purpose of this review is to ascertain the downsides
      of RALP by focusing on complications and limitations of this approach. EVIDENCE
      ACQUISITION: A Medline search of the English-language literature was performed to
      identify all papers published since 2001 relating to RALP. Papers providing data
      on technical failures, complications, learning curve, or other downsides of RALP
      were considered. Of 412 papers identified, 68 were selected for review based on
      their relevance to the objective of this paper. EVIDENCE SYNTHESIS: RALP has the
      following principal downsides: (1) device failure occurs in 0.2-0.4% of cases;
      (2) assessment of functional outcome is unsatisfactory because of nonstandardised
      assessment techniques; (3) overall complication rates of RALP are low, although
      higher rates are noted when complications are reported using a standardised
      system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a
      steep learning curve exists, and although acceptable operative times can be
      achieved in <20 cases, positive surgical margin (PSM) rates may require
      experience with >80 cases before a plateau is achieved; (6) robotic assistance
      does not reduce the difficulty associated with obese patients and those with
      large prostates, middle lobes, or previous surgery, in whom outcomes are less
      satisfactory than in patients without such factors; (7) economic barriers prevent
      uniform dissemination of robotic technology. CONCLUSIONS: Many of the downsides
      of RALP identified in this paper can be addressed with longer-term data and more
      widespread adoption of standardised reporting measures. The significant learning
      curve should not be understated, and the expense of this technology continues to
      restrict access for many patients.

PMID- 20036785
TI  - Changes in the expression of the miu-opioid receptor in the mare oviduct during
      oestrus and anoestrus.
AB  - The presence of the mu-opioid receptor (MOR) was investigated in the mare oviduct
      during oestrus and anoestrus, by means of immunoblotting and
      immunohistochemistry. Immunoblotting analysis showed that the MOR protein is
      expressed as 65, 50 and 30 kDa forms in the infundibulum and ampulla both in
      oestrus and anoestrus, while the 30 kDa form is absent in the isthmus. Moreover,
      different levels of expression were observed along the ampulla in the two periods
      examined. Immunohistochemistry revealed MOR in the mucosal epithelium, stromal
      cells, myocytes and blood vessels. Ciliated cells expressed MOR in the apical
      cytoplasm and, except for the isthmus of oestrous mares, also in the nucleus. Non
      ciliated cells showed MOR only in the isthmus segment during oestrus. Stromal
      cells showed different immunoreactivity along the oviduct segments and during the
      oestrous and anoestrous phases. The myosalpinx displayed immunostained myocytes
      in the intrinsic musculature of the ampulla and in the extrinsic and intrinsic
      musculature of the isthmus without significant differences between anoestrus and
      oestrus. Blood vessels expressed MOR in endothelial cells and smooth muscle cells
      in the isthmus myosalpinx of oestrous mares only. In conclusion, these findings
      show diverse MOR expression in the three segments constituting the oviduct, as
      well as changes in MOR expression linked to the mare's physiological condition.

PMID- 20036786
TI  - The human papillomavirus (HPV) vaccine, HPV related diseases and cervical cancer
      in the post-reproductive years.
AB  - Prophylactic HPV vaccines have demonstrated high efficacy against a range of HPV
      related diseases. They have been widely adopted as population health
      interventions in many jurisdictions and their routine use has been endorsed by
      the WHO. The development of these vaccines comes after an increased understanding
      of the natural history and epidemiology of HPV infection and disease in both
      males and females. Persistent HPV infection with oncogenic types induces
      malignant transformation in a range of epithelia including the cervix, anogenital
      regions, the penis and a number of head and neck sites. In relation to HPV
      disease prevention in the post-reproductive years, most infections occur soon
      after commencement of sexual activity but new infections do occur throughout the
      age spectrum. This reduces the likely impact of prophylactic vaccines in this
      population. The major impact on HPV related disease in this age group will come
      from advances in screening and early detection of HPV and neoplastic precursors.
      The most appropriate prevention for any individual man or women in this age group
      will be an individualised combination of vaccination, screening and early
      detection depending on the individual's own circumstances.

PMID- 20036787
TI  - Identifying and preventing chronic disease in an ageing world.

PMID- 20036788
TI  - Controlled research utilizing a basic all-metal detector in the search for buried
      firearms and miscellaneous weapons.
AB  - Incorporating geophysical technologies into forensic investigations has become a
      growing practice. Oftentimes, forensic professionals rely on basic metal
      detectors to assist their efforts during metallic weapons searches. This has
      created a need for controlled research in the area of weapons searches,
      specifically to formulate guidelines for geophysical methods that may be
      appropriate for locating weapons that have been discarded or buried by criminals
      attempting to conceal their involvement in a crime. Controlled research allows
      not only for testing of geophysical equipment, but also for updating search
      methodologies. This research project was designed to demonstrate the utility of
      an all-metal detector for locating a buried metallic weapon through detecting and
      identifying specific types of buried metal targets. Controlled testing of 32
      buried targets which represented a variety of sizes and metallic compositions
      included 16 decommissioned street-level firearms, 6 pieces of assorted scrap
      metals, and 10 blunt or bladed weapons. While all forensic targets included in
      the project were detected with the basic all-metal detector, the size of the
      weapon and surface area were the two variables that affected maximum depth of
      detection, particularly with the firearm sample. For example, when using a High
      setting the largest firearms were detected at a maximum depth of 55 cm, but the
      majority of the remaining targets were only detected at a maximum depth of 40 cm
      or less. Overall, the all-metal detector proved to be a very good general purpose
      metal detector best suited for detecting metallic items at shallow depths.

PMID- 20036789
TI  - Cathinone preservation in khat evidence via drying.
AB  - A primary concern with the forensic analysis of the khat plant (Catha edulis) has
      been the need to preserve the principle psychoactive component, cathinone, which
      converts to the less-active substance, cathine, after harvesting. The loss of
      cathinone has serious legal implications since it is a Schedule I controlled
      substance under federal regulations in the United States, while cathine is
      Schedule IV. A common misconception is that cathinone is highly unstable once the
      plant is harvested, and may be undetectable upon drying and prolonged storage.
      However, drying the plant material will preserve cathinone. Numerous seizures of
      a dried form of khat (referred to as "graba" in the United States) have been made
      in recent years, suggesting that drying the plant material is a viable approach
      to preserve khat evidence for both storage and reanalysis. A qualitative and
      quantitative study of the composition of khat samples seized as dried plant
      material has found the khat alkaloids to be relatively stable for a monitored
      period of 3 years, and cathinone has remained identifiable while stored at room
      temperature for over 10 years. Studies of green khat (received moist) have also
      determined that drying the moist leaves at either room temperature or by the
      application of heat are suitable methods to preserve cathinone in the dried
      material. These findings demonstrate that cathinone persists in dried khat for a
      time frame of several years, and simple drying techniques are an effective means
      to preserve seized khat evidence for long-term storage.

PMID- 20036790
TI  - Sudden onset sensorineural hearing loss caused by meningeal carcinomatosis
      secondary to occult malignancy: report of two cases.
AB  - Meningeal carcinomatosis (MC) is an uncommon form of metastasis of solid tumors.
      In the absence of clinical meningeal or parenchymal involvements, the
      sensorineural hearing loss (SNHL) as the starting symptom of MC is very
      infrequent. We report the history of two patients affected by MC who presented
      first with progressive SNHL. In both cases the early magnetic resonance imaging
      (MRI) finding mimicked bilateral masses in the cerebellopontine angle (CPA). Only
      the histopathologic result and surgical biopsy in cases 1 and 2, respectively,
      identified masses secondary to occult malignancy. However the available
      investigations could not discover the primary site of metastatic carcinoma.
      Despite the poor prognosis, because of the rarity and severity of MC we consider
      important to make known our experience in order to consider metastatic tumors in
      the differential diagnosis for sudden SNHL.

PMID- 20036791
TI  - Expression of CC-chemokine receptor 7 (CCR7) and CXC-chemokine receptor 4 (CXCR4)
      in head and neck squamous cell carcinoma.
AB  - OBJECTIVES: We tried to clarify the correlation of the expression of CCR7 and
      CXCR4 with lymph node and distant metastasis. MATERIALS AND METHODS: We examined
      expression of CCR7 and CXCR4 in 9 HNSCC cell lines and 25 HNSCC tissues by semi
      quantitative RT-PCR and immunohistochemistry study. We examined the expression
      levels of CCR7 and CXCR4 in undifferentiated and differentiated human normal
      keratinocyte. RESULTS: All cell lines expressed CCR7 mRNA, and three expressed
      CXCR4 mRNA. CCR7 and CXCR4 mRNAs were significantly higher in HNSCC tissues than
      in non-neoplastic tissues (p<0.05, respectively) and correlated with lymph node
      metastasis (p<0.05, respectively). The level of CXCR4 mRNA also correlated with
      distant metastasis (p<0.05). Immunohistochemistry demonstrated localization of
      CCR7 and CXCR4 to carcinoma cells and lymphocytes and immunohistochemical
      staining scores of CCR7 and CXCR4 also showed similar correlation to lymph node
      and distant metastasis with CCR7 and CXCR4 mRNA levels. The level of CCR7 mRNA
      was significantly higher in poorly and moderately differentiated than in well
      differentiated HNSCC (p<0.05). The level of CCR7 mRNA in undifferentiated
      keratinocyte was significantly higher than that in differentiated keratinocyte.
      CONCLUSION: The expression of CCR7 in HNSCC increases by dedifferentiation and
      plays an important role in lymph node metastasis of HNSCC and CXCR4 plays an
      important role in lymph node metastasis as well as distant metastasis.

PMID- 20036792
TI  - Clinical analysis of presbylarynx--vocal fold atrophy in elderly individuals.
AB  - OBJECTIVE: The proportion of elderly Japanese is increasing significantly and
      aging society greatly influences the medical services. The number of elderly
      patients who visited out Voice Outpatient Clinic has been increasing in recent
      years. The aim of the present study was to analyze the trend in the number of
      patients with aging-related vocal fold atrophy, and to assess the characteristics
      of senile change of vocal function. METHODS: A retrospective review of the 1999
      2005 medical records of patients aged > or =65 years was conducted, and patients
      with presbylarynx were analyzed. We evaluated age, sex, occupation, maximal
      phonation time (MPT), and mean airflow rate (MFR) during comfortable phonation to
      assess the physiological characteristics of senile change of vocal function. We
      compared MFR of presbylarynx with those of normal elderly person. RESULTS: The
      number of patients aged > or =65 who visited our clinic in the 7-year study
      period was 361, and 72 (20%) were diagnosed with vocal fold atrophy. They
      included 47 (65%) men and 25 (35%) women, with a mean age of 71 years (range, 65
      89). Among these patients, 27 (38%) were still employed at the time of
      consultation, while 17 (24%) were retired, at least 26 jobs required voice
      skills; and 15 patients (21%) were involved in singing and recitation of poems.
      MPT correlated negatively with age, while MFR correlated positively with age.
      CONCLUSION: The number of elderly patient with vocal fold atrophy increased
      gradually almost every year. The male patients account for 65%. Thirty-three
      percent of patient of the present study with presbylarynx were still in the
      workforce. MFR correlated positively and significantly with age. MFR was higher
      in presbylarynx than normal elderly person.

PMID- 20036793
TI  - Colorimetric detection of mutations in epidermal growth factor receptor using
      gold nanoparticle aggregation.
AB  - We have detected mutations in the epidermal growth factor receptor (EGFR) of non
      small cell lung cancer cells using the selective aggregations of gold
      nanoparticles. Mutations in exon 19 and exon 21 of EGFR gene were detected in non
      amplified genomic DNAs that were isolated from both the lung cancer cell lines
      and the cancer tissues of non-small cell lung cancer patients. At the optimal
      salt concentration, addition of the mutant DNA that was hybridized with the
      complementary probe into the suspension of unmodified gold nanoparticles caused
      the substantial aggregation of the gold nanoparticles and the color change of
      solution. Gold nanoparticles, however, did not exhibit significant aggregation,
      and the solution color remained unchanged with the addition of the wild type DNA
      that was hybridized with the probe. In the eight specimens from non-small cell
      lung cancer patients, we could detect the in-frame deletion mutant form in exon
      19 and the L858R point mutation in exon 21 by selective aggregation with gold
      nanoparticles. These results were also confirmed by an independent direct
      sequencing method using a DNA analyzer. We found that selective aggregation with
      gold nanoparticles could be successfully applied to direct detection of EGFR
      mutations in non-amplified genomic DNAs.

PMID- 20036795
TI  - Severe respiratory signs in two cats following the inhalation of a footwear
      proofing aerosol.

PMID- 20036794
TI  - Inflammation and oncogenesis: a vicious connection.
AB  - Epidemiological and experimental data suggest a close connection between
      inflammation and tumorigenesis. Solid tumors are typically infiltrated with
      immune cells and inflammation impacts most, if not all, stages of tumorigenesis.
      Molecular and cellular pathways, which connect inflammation and cancer, have
      emerged as attractive targets for prevention and therapy. In this review we
      discuss general mechanisms and concepts of cancer promoting inflammation.

PMID- 20036796
TI  - A case of Maffucci syndrome.
AB  - The Maffucci syndrome consists of a combination of multiple enchondromas and
      haemangiomas. It appears in the first two decades of life, with no family
      history. In this case we are reporting about a 26-year-old female who had
      suffered from multiple enchondromas since the age of two. At the age of nine, the
      patient presented with additional haemangiomas, which facilitated making proper
      diagnosis. She now presents with a massive lesion of her left upper extremity.
      The patient had initially rejected operative treatment when the disease was at
      early stages. At later stages, a more complex reconstruction of the hand would
      have been necessary to secure hand function. This procedure that sometimes
      induces a risk related to potential necessity of blood transfusion was rejected
      by the patient for religious reasons. Amputation of the extremity was therefore
      the last resort procedure.

PMID- 20036797
TI  - Taste disorders in cancer patients: pathogenesis, and approach to assessment and
      management.
AB  - Taste dysfunction in cancer patients impacts quality of life and impairs oral
      intake, which may have broader implications consisting of weight loss and
      nutritional compromise. These consequences may in turn affect broad symptom
      clusters including tissue healing, energy levels and mood. Patient evaluation and
      management should include a complete patient history and examination, and may
      require special tests. Patient-reported outcomes together with taste and smell
      testing are often necessary for diagnosis and management of taste disorders.
      Understanding, prevention and management of taste disorders in cancer patients
      requires continuing study. Current practice and recommendations are based on
      limited evidence. Due to its potentially significant impact on quality of life
      during and following cytotoxic therapy, and considering the increase in cancer
      survivorship, further research on this topic is imperative.

PMID- 20036798
TI  - Fungal pattern-recognition receptors and tetraspanins: partners on antigen
      presenting cells.
AB  - Fungal pattern-recognition receptors (F-PRRs), including C-type lectins, Toll
      like receptors, scavenger receptors and Fc/complement receptors, are crucial for
      inducing anti-fungal immune responses by antigen-presenting cells. The recent
      identification of specific F-PRR interactions with tetraspanins has shed new
      light on the functioning of F-PRRs in the cell membrane and subsequent downstream
      signaling. Tetraspanins are small four-transmembrane proteins that can assemble
      immune receptors and signaling molecules into functional membrane microdomains.
      Here, we discuss the implications of this novel type of interaction between F
      PRRs and tetraspanins in different subsets of antigen-presenting cells. We
      postulate that upon fungal binding tetraspanins modulate the function of F-PRRs
      by their recruitment into tetraspanin microdomains, leading to immune activation
      or tolerance.

PMID- 20036799
TI  - Darwinian interventions: taming pathogens through evolutionary ecology.
AB  - From the seemingly inevitable emergence of antibiotic resistance following drug
      use to the necessity of annual influenza vaccine updates, the ability of
      pathogens to evolve appears to preclude the development of effective, long-term
      interventions for many diseases. Despite this gloomy forecast, recent research
      explores how various principles and concepts from evolutionary ecology might
      inform practical attempts to bring these disease-causing agents under greater
      human control. By utilizing evolutionary and ecological information at various
      scales, these works investigate some promising avenues of disease intervention,
      from trapping pathogens in evolutionary dead ends, through slowing or inhibiting
      the process of pathogen adaptation, to more accurate forecasting of pathogen
      evolutionary trajectories. Thus, an evolutionary ecology perspective might
      ultimately provide powerful new tools in the pursuit of enduring solutions to the
      problem of treatment-driven pathogen evolution.

PMID- 20036800
TI  - This is linear verrucous epidermal nevus, not acanthosis nigricans.

PMID- 20036802
TI  - Role of the hepatitis B virus proteins in pro- and anti-apoptotic processes.
AB  - The Hepatitis B virus (HBV) can induces severe liver diseases as chronic
      hepatitis and hepatocellular carcinoma. Actually, apoptosis can play an important
      role in the progress of these diseases. As apoptosis goes through various
      extrinsic or intrinsic pathways, with activation of caspases and the possible
      involvement of mitochondria, HBV proteins can interfere with the various
      apoptosis processes. So far, four HBV proteins were reported to have such effect:
      the Large envelope protein, a truncated form of the Middle envelope protein, the
      HBx protein and HBSP, a protein generated from a spliced mRNA. In addition, our
      recent results suggest that indirectly the precore protein could have a function
      in apoptosis. This review focuses on the putative roles of HBV proteins as pro-
      or anti-apoptotic factors and the relationship which could exist with the HBV
      life cycle.

PMID- 20036801
TI  - Alpha-hemoglobin stabilizing protein: molecular function and clinical
      correlation.
AB  - The discovery of alpha-hemoglobin stabilizing protein (AHSP), a chaperone for
      free alpha-hemoglobin (alpha-Hb), has provided a satisfactory solution to the
      perplexing problem of balanced globin levels for Hb production in erythroid cells
      in the face of a two-fold excess of alpha-globin to beta-globin gene dosage.
      Unmatched alpha-Hb is unstable and precipitates onto membranes, where the
      released heme exerts oxidative damages resulting in ineffective erythropoiesis
      and hemolytic anemia, the underlying causes of pathology in the hereditary anemia
      of beta-thalassemia. The interaction of alpha-Hb with AHSP involves surfaces
      normally employed in binding to beta-Hb. However, a conformational change to the
      AHSP-bound alpha-Hb results in an oxidized heme, but in a pocket that is now less
      exposed to the outside environment, thereby protecting against both peroxide
      induced heme loss and iron-induced redox reaction. Studies in both mice and
      humans indicate that reduction in AHSP can result in hematological pathology.
      Conversely, alpha-Hb variants that are compromised in their ability to bind with
      AHSP produce beta-thalassemia-like symptoms. Disease conditions like some forms
      of thalassemia that are directly associated with AHSP structural and/or
      functional defects can now be included within the category of chaperonopathies.

PMID- 20036803
TI  - Beneficial effects of Bacteroides fragilis polysaccharides on the immune system.
AB  - Bacterial colonization of the intestine is critical for the normal function of
      the mammalian immune system. However, the specific molecules produced by
      commensal bacteria that contribute to the modulation of the host immune system
      are largely uncharacterized. Polysaccharide A (PSA) produced by the ubiquitous
      human commensal, Bacteroides fragilis is a model symbiosis factor. PSA is capable
      of activating T cell-dependent immune responses that can affect both the
      development and homeostasis of the host immune system. Colonization of previously
      germ-free mice with B. fragilis alone is sufficient to correct the splenic
      Th1/Th2 imbalance found in germ-free mice. In addition, PSA can provide
      protection in animal models of colitis through repression of pro-inflammatory
      cytokines associated with the Th17 lineage. This review provides an overview of
      the immunologic properties of PSA including the mechanisms of immune system
      activation and the resulting immunomodulatory effects.

PMID- 20036804
TI  - The emerging role of telomere biology in cardiovascular disease.
AB  - A striking variability exists in the susceptibility, age of onset and pace of
      progression of cardiovascular diseases. This is inadequately explained by the
      presence or absence of conventional risk factors. Differences in biological aging
      might provide an additional component of the observed variability. Telomere
      length provides a potential marker of an individual's biological age, shorter
      telomeres reflect a more advanced biological age. Telomere length at birth is
      mainly determined by genetic factors. Telomere attrition occurs as a consequence
      of cellular replication and can be accelerated by harmful environmental factors
      such as oxidative stress. When telomeres reach a critical threshold the cell will
      enter senescence and becomes dysfunctional. Telomeres are remarkably shorter in
      patients with aging associated diseases, including coronary artery disease and
      chronic heart failure. In addition, numerous conventional cardiovascular risk
      factors are associated with shorter telomere length. If telomeres can be proven
      to be not only associated but also causally involved in the pathogenesis of
      cardiovascular disease it might provide exciting new avenues for the development
      of future preventive and therapeutic strategies.

PMID- 20036805
TI  - In vitro derivation of germ cells from embryonic stem cells.
AB  - Embryonic stem cells (ESCs) have the potential to differentiate into cells of all
      tissue types, as demonstrated by their capability to contribute to the
      development of all germ layers in chimeras and to form teratomas. Of interest,
      however, is the lack of evidence of gametogenic gonadal tissues within teratomas,
      such as testicular tubules or follicles. Although this may reflect the fact that
      in vivo germ cell development and subsequent gametogenesis are complex biological
      processes, the generation of putative primordial germ cells (PGCs) has been
      reported during the differentiation of mouse and human ESCs in in vitro systems.
      In addition, mouse ESCs can even lead to the development of putative gametes, but
      the efficiency of this process needs to be improved and the functionality of the
      gametes remains to be proven. Interest in the generation of fully functional
      gametes from ESCs lies in an experimental model fundamental to the study of
      reproductive biology, a potential unlimited source of oocytes as a reprogramming
      bioreactor, and perhaps even in therapeutic applications to overcome human
      reproductive problems.

PMID- 20036806
TI  - Functional genomics in identification of drug targets in Dupuytren's contracture.
AB  - Although functional genomics methods offer new viewpoint on molecular processes
      involved in particular pathological state, these methods, in particular
      proteomics, are still under-represented in Dupuytren's contracture research.
      However, several recent papers based on functional genomics technologies
      represent a breakthrough in studying Dupuytren's contracture as they revealed new
      molecular players that had been impossible to detect by traditional molecular
      biology methods. Using computational tools to provide biological context for such
      broad arrays of data accelerates the process of homing in on the potential
      molecular markers and drug targets. Interactomes, maps of protein-protein
      interactions characteristic for the disease and as such putative models of its
      molecular pathology, are especially useful for this purpose, facilitating the
      transition from global screening methods to specific experiments aimed at therapy
      development. The combination of these approaches in Dupuytren's contracture
      research might therefore facilitate the discovery of novel therapeutic targets
      and diagnostic markers indicative of disease progression.

PMID- 20036807
TI  - EGFR gene alterations as a prognostic biomarker in advanced esophageal squamous
      cell carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC) exhibits abnormalities in epidermal
      growth factor receptor (EGFR) gene. To identify a prognostic marker, the
      overexpression of EGFR protein, mutations in EGFR and p53 mutations were analyzed
      in pretreatment biopsy specimens removed from T3-4 and/or M1 LYM ESCC patients
      who received chemoradiotherapy. A silent mutation comprised of a single
      nucleotide polymorphism (SNP) at codon 787 of exon 20 of the EGFR gene was found
      in 19 patients (33%). In multivariate analysis, a significant difference was seen
      in the overall survival (odds ratio; 2.347, 95% confidence interval; 1.183-4.656,
      p = 0.015) between patients with and without the EGFR heterozygous genotype.
      Among the 57 eligible patients, 3-year survival rates was 21%, while in patients
      with EGFR heterozygous genotype the rate were 0%. However, neither overexpression
      of EGFR nor p53 mutations was associated with the overall survival. These results
      suggest that the EGFR SNP at codon 787 of exon 20 determined in pretreatment
      biopsy specimens may be a clinically useful biomarker for predicting the
      prognosis of ESCC patients.

PMID- 20036809
TI  - Activation of polyhydroxyalkanoates: functionalization and modification.
AB  - Polyhydroxyalkanoates (PHAs) serve numerous bacteria as storage compounds. It is
      generally believed that under unbalanced growth conditions, n-hydroxyalkanoates
      are synthesized inside the bacterial cells, polymerized to polyesters, and
      densely packed in granules. In the absence of extracellular carbon, the
      internally stored PHAs are depolymerized and consequently metabolized to enable
      cell maintenance and reproduction. However, some bacteria exhibit growth
      associated production and degradation of PHAs as part of the cell sustainment.
      This natural production and degradation cycle indicates that PHAs possess
      biodegradability and may have biocompatibility properties. Since the discovery
      that some bacteria can incorporate 3-hydroxyalkanoates bearing functional groups
      from related substrates, research has led to structural diversification of PHAs
      by biosynthesis and chemical modifications. A commonly applied route for
      tailoring PHAs is their in situ functionalization by biosynthetically producing
      side chains with terminal double bonds followed by chemistry. Non-functionalized
      PHAs can also be activated by surface modification techniques. The resulting
      tailor-made structural and material properties have positioned
      polyhydroxyalkanoates well to contribute to the manufacturing of second and third
      generation biomaterials.

PMID- 20036810
TI  - Role of Dps (DNA-binding proteins from starved cells) aggregation on DNA.
AB  - The review outlines the experimental studies that have led to the current
      understanding at a molecular level of the protective role exerted by Dps proteins
      under stress conditions. After a brief description of the structural signatures
      and of the ferroxidase activity, which confers to all Dps proteins the capacity
      to decrease the hydroxyl radical induced DNA damage, the interaction of some
      family members with DNA is analysed. Special emphasis is given to the Dps
      structural elements that render the interaction with DNA possible and to the
      consequences that complex formation has on nucleoid organization and microbial
      survival.

PMID- 20036808
TI  - Brain temperature homeostasis: physiological fluctuations and pathological
      shifts.
AB  - Brain temperature is a physiological parameter, reflecting the balance between
      metabolism-related intra-brain heat production and heat loss by cerebral
      circulation to the rest of the body and then to the external environment. First,
      we present data on brain temperature fluctuations occurring under physiological
      and behavioral conditions and discuss their mechanisms. Since most processes
      governing neural activity are temperature-dependent, we consider how naturally
      occurring temperature fluctuations could affect neural activity and neural
      functions. We also consider psychomotor stimulants and show that their
      hyperthermic effects are state-dependent and modulated by environmental
      conditions. Since high temperature could irreversibly damage neural cells and
      worsen various pathological processes, we consider the situations associated with
      pathological brain hyperthermia and evaluate its role in acute perturbations of
      brain functions, neurotoxicity, and neurodegeneration. We also discuss the
      limitations in consideration of brain temperature within the frameworks of
      physiological regulation and homeostasis. While different adaptive mechanisms
      could, within some limits, compensate for altered intra-brain heat balance, these
      mechanisms could fail in real-life situations, resulting in life-threatening
      health complications.

PMID- 20036811
TI  - PrP interactions with nucleic acids and glycosaminoglycans in function and
      disease.
AB  - Since the first description of prion diseases, great effort has been made toward
      comprehending this new paradigm in biology. Despite large advances in the field,
      many questions remain unanswered, especially concerning the conversion of PrP(C)
      into PrP(Sc). How this conformational transition evolves is a crucial problem
      that must be solved in order to attain further progress in therapeutics and
      prevention. Recent developments have indicated the requirement for partners of
      the prion protein in triggering the conversion. In the present review, we will
      explore the interaction of PrP with some of its most intriguing partners, such as
      sulfated glycans and nucleic acids. These molecules seem to play a dual role in
      prion biology and could be fundamental to explaining how prion diseases arise, as
      well as in the development of effective therapeutic approaches.

PMID- 20036814
TI  - TGF-beta signaling, tumor microenvironment and tumor progression: the butterfly
      effect.
AB  - Transforming growth factor-beta (TGF-beta) signals through receptor
      serine/threonine kinases and intracellular Smad effectors, regulating numerous
      epithelial cell processes. TGF-beta plays a crucial role in the cancer initiation
      and progression through tumor cell autonomous signaling and interactions with
      tumor microenvironment, but is featured with a butterfly effect upon the stages
      of tumorigenesis. TGF-beta signaling acts as a suppressor of epithelial cell
      tumorigenesis at early stages, but promotes tumor progression by enhancing
      migration, invasion, and survival of the tumor cells during the later stages. TGF
      beta signaling also cross-talks with other cell survival signaling pathways.
      Tumor microenvironment contains many distinct cell types, which substantially
      influences the tumor cell growth and survival, and the invasion and metastasis.
      TGF-beta in the microenvironment, produced by cancer and/or stromal cells, is
      high and negatively correlates with disease progression and patient prognosis.
      Therefore, TGF-beta may affect tumor progression by multiple mechanisms in
      addition to its direct action on tumor cells, and the diversities of TGF-beta
      signaling in tumors imply a need for caution to TGF-beta-targeted strategies of
      tumor prevention and/or therapeutics.

PMID- 20036812
TI  - Growth factors in tumor microenvironment.
AB  - Tumor microenvironment plays a critical role in tumor initiation and progression.
      Components in the microenvironment can modulate the growth of tumor cells, their
      ability to progress and metastasize. A major venue of communication between tumor
      cells and their microenvironment is through polypeptide growth factors and
      receptors for these growth factors. This article discusses three major classes of
      growth-stimulatory polypeptide growth factors and receptors for these growth
      factors. It also discusses how deregulation of these growth factors or their
      receptors can drive malignant transformation and progression.

PMID- 20036813
TI  - Cancer associated fibroblasts (CAFs) in tumor microenvironment.
AB  - Cancer associated fibroblasts (CAFs) is one of the most crucial components of the
      tumor microenvironment which promotes the growth and invasion of cancer cells by
      various mechanisms. CAFs demonstrate a high degree of heterogeneity due to their
      various origins; however, many distinct morphological features and physiological
      functions of CAFs have been identified. It is becoming clear that the crosstalk
      between the cancer cells and the CAFs plays a key role in the progression of
      cancer, and understanding this mutual relationship would eventually enable us to
      treat cancer patients by targeting CAFs. In this review, we will discuss the
      latest findings on the role of CAFs in tumorigenesis and metastasis as well as
      potential therapeutic implication of CAFs.

PMID- 20036815
TI  - Regulation of tumor angiogenesis by the local environment.
AB  - Angiogenesis is the process of formation of new blood vessels from pre-existing
      vessels or endothelial cell progenitors. It plays an essential role in
      embryogenesis, inflammation, wound healing, tumor growth and metastasis. The
      tumor microenvironment contains excessive amounts of pro-angiogenic factors
      derived from neoplastic, stromal, and infiltrating immune cells. The imbalance of
      pro-angiogenic and anti-angiogenic factors promotes abnormal angiogenesis,
      creating numerous blood vessels with structural abnormalities and functional
      defects. These defective vessels often create an inflammatory environment within
      the tumor that promotes coagulation, thrombosis, and impairs blood supply,
      causing further complications to the cancer patient. The structural and
      functional abnormalities of the tumor vessels promote hematogenous metastasis,
      which is strongly associated with shorter patient survival. Furthermore, tumor
      blood vessels are poorly perfused, which impedes drug delivery to the tumor, thus
      reducing the efficacy of anti-cancer agents. Tumor angiogenesis is widely studied
      as an important target for suppressing tumor growth and metastasis. This review
      will briefly summarize the current findings related to regulation of angiogenesis
      by the tumor microenvironment, while highlighting potential targets for
      inhibiting this process.

PMID- 20036816
TI  - The role of hypoxia and acidosis in promoting metastasis and resistance to
      chemotherapy.
AB  - By a multiplicity of mechanisms, hypoxia and acidosis create a nurturing
      environment for tumor progression and the evolution of metastatic, drug-resistant
      cells. Acidosis drives mutagenesis and promotes the subversion of checkpoints and
      apoptotic mechanisms. Hypoxic tissues secrete cytokines that undermine normal
      anti-tumor surveillance by macrophages, turning them into accomplices and
      facilitators of invasion and angiogenesis. Invasiveness is also abetted by
      acidosis, the result of shifting to an anaerobic glycolytic metabolism. These
      factors explain the generally poor prognosis indicated by tumors expressing
      hypoxia-inducible factor-1 (HIF-1). However, these insights into the physiology
      of hypoxic tumors have inspired the development of new chemotherapeutic
      approaches directed at these tissues, including bioreductive drugs and gene
      therapies, some of which are in clinical trials. The ability to target the
      hypoxic compartment should allow longer progression-free survival and overall
      survival of patients bearing solid tumor malignancies.

PMID- 20036818
TI  - Stroma-mediated expression of estrogen and its role in cancer.
AB  - Several hormones are well known for their role in tumorigenesis. Among them
      estrogen is the best characterized hormone. In particular, stromal tissue
      produced estrogen plays a key role in breast tumor development and progression,
      highlighting the importance of communications between stromal tissue and tumor
      cells in the tumor microenvironment. In this review, we update our current
      understanding of stroma-mediated expression of hormones (estrogen) and their role
      in tumorigenesis, focusing on how aromatase produced in stromal tissue affects
      tumor cell growth. We also briefly touch on hormone therapy involving selective
      estrogen receptor modulators and aromatase inhibitors.

PMID- 20036817
TI  - Role of myoepithelial cells in breast tumor progression.
AB  - Myoepithelial cells form a semi-continuous protective sheet separating the human
      breast epithelium and the surrounding stroma. They suppress stromal invasion of
      tumor cells by the secretion of various anti-angiogenic and anti-invasive
      factors. The disruption of this cell layer results in the release of the growth
      factors, angiogenic factors, and reactive oxygen species causing an alteration in
      the microenvironment. This helps in the proliferation of surrounding cells and
      increases the invasiveness of tumor cells. Two theories are proposed for the
      mechanism of tumor epithelial cells progression from in situ to invasive stage.
      According to the first theory, tumor cell invasion is triggered by the
      overproduction of proteolytic enzymes by myoepithelial cells and surrounding
      tumor cells. The second theory states that tumor invasion is a multistep process,
      the interactions between damaged myoepithelial cells and the immunoreactive cells
      trigger the release of basement membrane degrading enzymes causing tumor
      progression. Further studies in understanding of molecular mechanism of
      myoepithelial cell functions in tumor suppression may lead to the identification
      of novel therapeutic targets for breast cancer.

PMID- 20036819
TI  - A pharmacodynamic model of Aurora kinase inhibitors in the spindle assembly
      checkpoint.
AB  - Arguably the most dramatic phase in the cell cycle is mitosis, during which
      replicated chromosomes are sorted into two distinct sets. Aurora kinases are
      central to the accurate segregation of chromosomes during mitosis. Consequently,
      they have been selected as possible targets for cancer therapy. Anti-cancer drugs
      that target Aurora kinases are normally designed to inhibit their function. The
      complexity of the roles of Aurora kinases and their interaction with respective
      inhibitors means that it is often very difficult to obtain meaningful links
      between inhibitor concentration and efficacy using standard methods. To overcome
      these difficulties, we propose a novel mathematical modelling approach. We
      present a pharmacodynamic model that is able to encapsulate the key roles of two
      kinases, Aurora A and B, in the spindle assembly checkpoint. Moreover, the model
      is capable of qualitatively differentiating between the effects of inhibiting
      Aurora A, Aurora B and A plus B, respectively, by predicting cell behaviour.
      Consequently, predictions regarding the qualitative relationship between
      inhibitors, measurable biomarkers and cell damage can be obtained using this
      powerful modelling approach.

PMID- 20036820
TI  - Human thermoregulation: separating thermal and nonthermal effects on heat loss.
AB  - Human thermoregulatory control during heat stress has been studied at rest,
      during exercise and more recently during exercise recovery. Heat balance in the
      body is maintained by changes in the rate of heat loss via adjustments in skin
      blood flow and sweating. Independent of thermal control, the actions of
      nonthermal factors have important consequences in the control of heat loss
      responses during and following exercise. While the effect of these nonthermal
      factors is largely considered to be an inhibitory or excitatory stimulus which
      displaces the set-point about which temperature is regulated, their effects on
      human thermoregulatory control are far reaching. Many factors can affect the
      relative contribution of thermal and nonthermal influences to heat balance
      including exercise intensity, hemodynamic status, and the level of hyperthermia
      imposed. This review will characterize the physiological responses associated
      with heat stress and discuss the thermal and nonthermal influences on sweating
      and skin blood flow in humans. Further, recent calorimetric evidence for the
      understanding of thermal and nonthermal contributions to human heat balance will
      also be discussed.

PMID- 20036821
TI  - Immunoregulatory cells of the tumor microenvironment.
AB  - Current immune therapies for cancer have been disappointing. The various
      approaches to immunotherapy for cancer so far tried clinically include adoptive
      immunotherapy, vaccination strategies, and administration of anti-tolerogenic
      antibodies. Each of these approaches basically involves the inhibition or
      circumvention of immune tolerance, activating immune effectors that have the
      capability to recognize and lyse tumor. Unfortunately, only a relatively small
      population of patients respond to these therapies, and most of the responses are
      not durable. There is mounting evidence that immune interventions employing anti
      tolerogenic strategies are insufficient to control tumor, as the tumor
      microenvironment is generally immunosuppressive. The present review summarizes
      the current knowledge on the cellular constituents of tumor (excluding tumor
      cells themselves) that contribute to this immunosuppressive microenvironment.

PMID- 20036823
TI  - Dendritic cells as therapeutic agents against cancer.
AB  - Dendritic cells (DC) are antigen-presenting cells whose immunobiology has been
      proven to be central to the function of the immune system. Further understanding
      of these cells is leading the way to the manipulation of the immune system as a
      tool to cure and prevent a vast array of diseases including cancers. These cells
      have been used in trials as vaccine adjuvants in therapies that aim to break the
      body's tolerance to the tumor. From the first 1000 DC vaccinees in 2003 there has
      been a breadth of information on safety that is paving the way to the study of
      the efficiency of these therapies. This review aims to explore recent updates to
      the current literature on DC vaccine therapies in clinical trials and analyze
      their future. At this crossroads is where intricacies of the technique are being
      revised to explore the most efficient and effective parameters for the
      enhancement of DC adjuvant therapies.

PMID- 20036824
TI  - Expression of immune genes during metamorphosis of Xenopus: a survey.
AB  - This review focuses on what is known about the immune transcriptome during
      metamorphosis of Xenopus laevis and Silurana (Xenopus) tropicalis. This subject
      is of importance to obtain a global understanding of the physiological changes
      operating during metamorphosis. In turn, a good knowledge of the physiology of
      amphibian metamorphosis may contribute to the fight against amphibian decline and
      help the development of alternative toxicologic assays. By examining what is
      known on the expression of innate and adaptive immune genes during metamorphosis,
      it becomes clear that our knowledge of the anatomy of the tadpole "immunome" is
      fragmentary. Since a wealth of data sits in cDNA sequences, I am making a first
      attempt to enrich our knowledge on this subject. I exemplify that mining EST data
      can rapidly provide us with the necessary tools to unravel the cross-talk between
      thyroid hormone signalling during metamorphosis and larval immune system changes.

PMID- 20036822
TI  - Cancer vaccine development: designing tumor cells for greater immunogenicity.
AB  - Cancer vaccine development is one of the most hopeful and exhilarating areas in
      cancer research. For this reason, there has been a growing interest in the
      development and application of novel immunotherapies for the treatment of cancer
      with the focus being on stimulating the immune system to target tumor cells
      specifically while leaving normal cells unharmed. From such research has emerged
      a host of promising immunotherapies such as dendritic cell-based vaccines,
      cytokine therapies and gene transfer technology. These therapies seek to
      counteract the poor immunogenicity of tumors by augmenting the host's immune
      system with a variety of immunostimulatory proteins such as cytokines and
      costimulatory molecules. While such therapies have proven effective in the
      induction of anti-tumor immunity in animal models, they are less than optimal and
      pose a high risk of clinical infeasibility. Herein, we further discuss these
      immunotherapies as well as a feasible and efficient alternative that, in pre
      clinical animal models, allows for the expression of specific immunostimulatory
      molecules on the surface of tumor cells by a novel protein transfer technology.

PMID- 20036825
TI  - A decade in search of myopia genes.
AB  - Nearly half of visual impairment in the world is caused by uncorrected refractive
      errors, and myopia constitutes a significant proportion of this problem.
      Moreover, the prevalence of myopia is increasing, especially in Asian countries.
      Linkage studies have identified at least 18 possible loci (MYP) in 15 different
      chromosomes associated with myopia, although some of these remain to be
      confirmed. However, when studies have been carried out to identify specific
      candidate genes, it is apparent that these genes are often not part of MYP loci.
      In studying the expression of specific genes that might be responsible for
      myopia, we are learning that the involvement of various small leucine-rich repeat
      proteoglycans and growth factors is not a simple one. The emerging picture is one
      of complex interaction, in which mutations in several genes likely act in
      concert. The majority of myopia cases are not likely caused by defects in
      structural proteins, but in defects involving the control of structural proteins.
      The future of genetic research in this area will likely rely increasingly on
      microchip array technology.

PMID- 20036826
TI  - Methods and models in neurodegenerative and systemic protein aggregation
      diseases.
AB  - Protein misfolding and aggregation are implicated in a wide range of increasingly
      prevalent human diseases ranging from dementia to diabetes. In this review we
      discuss the current experimental strategies that are being employed in the
      investigation of the pathogenesis of three important protein misfolding
      disorders. The first, Alzheimer's disease (AD), is the most prevalent
      neurodegenerative disease and is thought to be initiated by the aggregation of a
      natively unstructured peptide called amyloid beta (Abeta). We discuss methods for
      the characterization of the aggregation properties of Abeta in vitro and how the
      results of such experiments can be correlated with data from animal models of
      disease. We then consider another form of amyloidosis, where a systemic
      distribution of amyloid deposit is caused by aggregation and deposition of
      mutational variants of lysozyme. We describe how experiments in vitro, and more
      recently in vivo, have provided insights into the origins of this disease.
      Finally we outline the varied paradigms that have been employed in the study of
      the serpinopathies, and in particular, a dementia caused by neuroserpin
      polymerization.

PMID- 20036827
TI  - Drug delivery systems for potential treatment of intracellular bacterial
      infections.
AB  - Despite the advent of a considerable number of new antibiotics, treatment of
      intracellular pathogens still represents a major pharmaceutical challenge. The
      antibiotic concentration in those specialized niches are often subtherapeutic,
      for which high doses of antibiotics must often be used. This is not only costly
      but may also increase localized or systemic side effects. There is therefore an
      urgent need for materials and methods to enable clinicians to achieve
      therapeutically effective intracellular concentration of those antibiotics which
      show good efficiency in vitro. In this setting, the possible use of drug delivery
      systems (DDS) loaded with antibiotics that exhibit a high in vitro bactericidal
      activity deserves to be considered. Entrapping or encapsulating the drug within a
      delivery system provides a greater control of the pharmacokinetic behavior of the
      active molecule. This more efficient use of antibiotics may diminish their
      drawbacks and provide the basis for shortening the current time required by
      classical treatments. This review will focus on the role of DDS as a potential
      tool against intracellular bacteria.

PMID- 20036828
TI  - DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's
      disease.
AB  - Emerging evidences on the nuclear localization of alpha-Synuclein in neurons and
      a close look in to its primary sequence/structural organization led us to examine
      its DNA binding ability. Subsequently, we first time demonstrated the interaction
      of DNA with alpha-Synuclein which was also confirmed by others. We recently
      showed that double-stranded oligos induce partial folding in alpha-Synuclein and
      promote its aggregation, where as single-strand circular DNA and supercoiled
      plasmid DNA induced a helix-rich conformation and protected the protein from
      fibrillation. In turn, alpha-Synuclein modulates DNA conformation from B- to an
      altered B-form, which may affect DNA transactions. Interestingly, amyloid-beta
      peptides and prion proteins implicated in Alzheimer's disease and Prion diseases
      respectively, were also shown to have DNA binding activity which suggests that
      DNA binding may be a common property of many amyloidogenic proteins associated
      with various neurodegenerative disorders. In this review, we debate the
      biological significance of DNA-alpha-Synuclein interactions; it's beneficial vs.
      toxic role in relevance to Parkinson's disease.

PMID- 20036829
TI  - Mitochondrial DNA mutations in cancer--from bench to bedside.
AB  - Mitochondria are cell organelles mostly known for their production of ATP through
      oxidative phosphorylation. As suggested over 70 years ago by O. Warburg and
      recently confirmed with molecular techniques, alterations in respiratory activity
      and mitochondrial DNA appear to be a common feature of malignant cells. Somatic
      mtDNA mutations have been reported in many types of cancer cells. MtDNA mutation
      pattern may enhance the specificity of cancer diagnostics, detection and
      prediction of tumor growth rate and patients' outcome. Therefore it may be used
      as a molecular cancer bio-marker. Nevertheless recently published papers list a
      large number of mitochondrial DNA mutations in many different cancer types, but
      their role in cell pathophysiology remains unsummarized. This review covers the
      consequences of mitochondrial genes mutations for human cell physiology and
      proliferation. We underline effects of mtDNA mutation-resulting amino acid
      changes in the respiratory chain proteins' structure, and propose changes in
      mitochondrial protein function. Mutations are critically evaluated and
      interpreted in the functional context and clinical utility of molecular
      mitochondrial research is summarized and new perspectives for 'mitochondrial
      oncology' suggested.

PMID- 20036831
TI  - Leukocyte transmigration across the blood-brain barrier: perspectives on
      neuroAIDS.
AB  - Leukocyte trafficking serves a critical function in central nervous system (CNS)
      immune surveillance. However, in many disease states leukocyte entry into the CNS
      is increased, which can disrupt the blood-brain barrier (BBB) and propagate
      neuroinflammation. These pathologic processes result in BBB permeability, glial
      activation, and neuronal compromise, all of which contribute to CNS damage. The
      resulting neuronal injury and loss are characteristic of many neuroinflammatory
      conditions including Alzheimer disease, multiple sclerosis, HIV-1 encephalopathy,
      sepsis, ischemia and reperfusion, and CNS tumors. HIV-1 encephalopathy is unique
      among these processes in that viral activity exacerbates CNS immune dysregulation
      and promotes chronic neuroinflammation and neurodegeneration. Thus, a significant
      number of HIV-1-infected persons exhibit neurocognitive and/or motor impairment.
      This review discusses the mechanisms that regulate leukocyte recruitment into the
      CNS and how HIV-1 infection dysregulates this process and contributes to
      neuropathology. Experimental BBB models to study leukocyte transmigration and the
      potential of targeting this transmigration across the BBB as a therapeutic
      strategy are also discussed.

PMID- 20036832
TI  - WHAT do viruses BET on?
AB  - The bromodomain and ET domain (BET) proteins belong to a group of bromodomain
      proteins and bind acetylated histones. Two of the currently known members of this
      protein family were implicated in transcriptional regulation. The two most
      studied BET proteins Brd2 and Brd4 have been shown to bind to viral proteins of
      herpesviruses and papillomaviruses. These pathogens often take advantage of the
      cellular function of the BET proteins and exploit it for their own purposes. In
      some cases though, viral proteins were shown to adapt BET proteins to new virus
      specific functions. Additionally some retroviruses seem to encode proteins that
      mimic Brd4 functions and hijack Brd4-associated protein complexes to use them for
      their own transcription.

PMID- 20036830
TI  - Stem cells as a therapeutic target for diabetes.
AB  - The rapidly increasing number of diabetes patients across the world poses a great
      challenge to the current therapeutic approach. The traditional method of
      exogenous supply of insulin has ephemeral effect and often causes lethal
      hypoglycemia that demands to develop a novel strategy. Recent investigations on
      regeneration of insulin producing cells (IPCs) revealed that in addition to
      primary source i.e., pancreatic beta cells, IPCs can be derived from several
      alternative sources including embryonic, adult, mesenchymal and hematopoietic
      stem cells via the process of proliferation, dedifferentiation, neogenesis,
      nuclear reprogramming and transdifferentiation. There is considerable success in
      insulin independency of diabetes patient after transplantation of whole pancreas
      and/or the islet cells. However, the major challenge for regenerative therapy is
      to obtain a large source of islet/beta cells donor. Recent advances in the
      directed differentiation of stem cells generated a promising hope for a better
      and permanent insulin independency for diabetes. In this review we discussed stem
      cells as a potential future therapeutic target for the treatment of diabetes and
      associated diseases.

PMID- 20036833
TI  - Aptamers to explore prion protein interactions with nucleic acids.
AB  - A misfolded isoform of the prion protein (PrP) is the essential component of the
      prion diseases' agent. The prion concept has progressively gained acceptance, in
      a large part thanks to the realization that it played a role not only in the
      transmissible spongiform encephalopathies, but also in the non-Mendelian
      propagation of self-perpetuating phenotypes of the yeast Saccharomyces
      cerevisiae. Uncertainties about the nature of the agent and the function of PrP
      have fostered searches of nucleic acid ligands of the protein. In vitro methods
      of nucleic acid evolutions have been used to identify RNAs or DNAs that bind PrP,
      towards the triple objective of i) setting up new diagnostic tools, ii)
      identifying nucleic acids with which PrP may interact, as part of its
      physiological or pathological function, and iii) elucidating the pathological
      transconformation of PrP. This review will focus on these studies, their methods,
      the knowledge acquired from them about the prion protein, and the possibilities
      that they offer in the areas of diagnosis and therapy of prion diseases.

PMID- 20036834
TI  - The circadian rhythm of body temperature.
AB  - This article reviews the literature on the circadian rhythm of body temperature.
      It starts with a description of the typical pattern of oscillation under standard
      laboratory conditions, with consideration being given to intra- and interspecies
      differences. It then addresses the influence of environmental factors
      (principally ambient temperature and food availability) and biological factors
      (including locomotor activity, maturation and aging, body size, and reproductive
      state). A discussion of the interplay of rhythmicity and homeostasis (including
      both regulatory and heat-exchange processes) is followed by concluding remarks.

PMID- 20036835
TI  - Mouse models demonstrating the role of stem/progenitor cells in gastric
      carcinogenesis.
AB  - Advances have been made in identifying the gastric epithelial stem cells and
      their immediate descendents which act as uncommitted or committed progenitors
      giving rise to cell lineages producing the various contents of the gastric juice
      and several hormones. New research suggests that these epithelial stem/progenitor
      cells also play an important role in the development of gastric cancer. In this
      review, we summarize results of examining three genetically manipulated mouse
      models in which the biological features and differentiation program of the
      gastric stem/progenitor cells were altered by three different approaches: 1)
      knockout of the trefoil factor 1 gene which is expressed initially in the
      partially committed pre-pit cell progenitors known to produce both mucus- and
      acid-secreting cell lineages, 2) expression of Simian virus 40 large T antigen
      gene in the acid-secreting parietal cell lineage, and 3) ablation of the parietal
      cells by using the attenuated diphtheria toxin A fragment. Systematic analysis of
      these animal models provided some clues to the role played by gastric
      stem/progenitor cells during carcinogenesis and to the cellular origin of gastric
      cancer.

PMID- 20036836
TI  - The interrelationship between sleep regulation and thermoregulation.
AB  - The circadian distribution of vigilance states and body temperature changes are
      tightly coupled. The increase in heat loss at the end of the day is associated
      with increased ease to fall asleep. Experimental data show that warming the skin
      or the brain can increase sleep propensity, sleep consolidation, and the duration
      of sleep. Anatomical and neurophysiological studies show that the pre-optic
      anterior-hypothalamus (POAH) is the main integrator of sleep and thermoregulatory
      information. It integrates information on vigilance states, body temperature, and
      environmental temperature and influences vigilance states and body temperature in
      response. Animals that display daily torpor may be a valuable model to
      investigate the relationship between sleep and thermoregulation. During torpor
      these animals seem to apply similar strategies and physiological processes as
      humans during entrance into sleep, but in a more extreme way, providing an
      excellent opportunity to investigate these processes in more detail. More
      systematic investigations are needed to further our understanding of the
      relationship between sleep and thermoregulation, and may provide the basis to
      treat sleep disturbances with thermal strategies.

PMID- 20036837
TI  - Chondroitin sulfate proteoglycans in neural development and plasticity.
AB  - PTPzeta and lectican family members are major chondroitin sulfate proteoglycans
      (CS-PGs) in the brain, which bind with many proteins via core protein and CS
      portions. Recent studies revealed that the oversulfated structures in CS
      constitute high affinity binding sites for various growth factors and axon
      guidance molecules, and play important roles in the proliferation of neural
      progenitor cells, neurite extension and neuronal migration. PTPzeta uses
      pleiotrophin as a ligand. The CS portion of PTPzeta constitutes a part of the
      pleiotrophin-binding site, and oversulfated D unit increases the binding
      affinity. Pleiotrophin-PTPzeta signaling regulates the morphogenesis of Purkinje
      cell by controlling the tyrosine phosphorylation of a Notch-related transmembrane
      protein, DNER. In the brain of adult animals, a subset of neurons are surrounded
      by CS-PG-rich extracellular matrix called perineuronal net, in which lecticans
      form complexes with hyaluronic acid and tenascin-R. CS-PGs in the perineuronal
      net regulate ocular dominance plasticity in the visual cortex by enhancing the
      uptake of Otx2 homeoprotein by parvalbumin-positive interneurons in a CS
      dependent manner. These studies revealed unexpectedly complex mechanisms of CS-PG
      functions.

PMID- 20036838
TI  - Chemokine patterning by glycosaminoglycans and interceptors.
AB  - Chemokines mediate leukocyte emigration from blood into tissues. This process is
      triggered by chemokines binding and signaling through their cognate G-protein
      coupled receptors on leukocytes and requires the involvement of leukocyte and
      endothelial cell adhesion molecules. Additionally, in vivo chemokine activity
      depends on their interaction with "auxiliary" molecules expressed by the vascular
      endothelial cells. Secreted chemokines can be immobilized on the luminal and
      abluminal endothelial cell surfaces by glycosaminoglycans. In order to be
      targeted to their presentation sites on the luminal endothelial cell surface, the
      tissue-derived chemokines have to cross the endothelial cell barrier. For
      inflammatory chemokines this is accomplished by active transport involving Duffy
      antigen, an 'interceptor' expressed by venular endothelial cells. Other chemokine
      interceptors, D6 in particular, may act as scavenging decoys and are involved in
      clearance of chemokines. The interceptor-mediated transport or elimination of
      chemokines, together with their immobilization by glycosaminoglycans, lead to
      chemokine patterning at the blood-tissue interface and within tissues. The
      resulting chemokine gradients induce leukocyte emigration from blood and may also
      be necessary for directed leukocyte migration within tissues.

PMID- 20036839
TI  - Modeling calcium waves in cardiac myocytes: importance of calcium diffusion.
AB  - Under certain conditions, cardiac myocytes engage in a mode of calcium signaling
      in which calcium release from the sarcoplasmic reticulum (SR) to myoplasm occurs
      in self-propagating succession along the length of the cell. This event is called
      a calcium wave and is fundamentally a diffusion-reaction phenomenon. We present a
      simple, continuum mathematical model that simulates calcium waves. The framework
      features calcium diffusion within the SR and myoplasm, and dual modulation of
      ryanodine receptor (RyR) release channels by myoplasmic and SR calcium. The model
      is used to illustrate the effect of varying RyR permeability, sarco/endoplasmic
      reticulum Ca2+ ATPase (SERCA) activity and calcium ion mobility in myoplasm and
      SR on wave velocity. The model successfully reproduces calcium waves using
      experimentally-derived variables. It also supports the proposal for wave
      propagation driven by the diffusive spread of myoplasmic calcium, and highlights
      the importance of SR calcium load on wave propagation.

PMID- 20036840
TI  - Interhemispheric synchrony in visual cortex and abnormal postnatal visual
      experience.
AB  - The question of whether neural synchrony may be preserved in adult mammalian
      visual cortex despite abnormal postnatal visual experience was investigated by
      combining anatomical and computational approaches. Single callosal axons in
      visual cortex of early monocularly deprived (MD) adult cats were labeled
      anterogradely with biocytin in vivo and reconstructed in 3D. Spike propagation
      was then orthodromically simulated within each of these axons with NEURON
      software. Data were systematically compared to those previously obtained in
      normally reared (NR) adult cats with comparable approaches. The architecture of
      the callosal axons in MD animals differed significantly from the NR group, with
      longer branches and first nodes located deeper below the cortex. But,
      surprisingly, simulation of spike propagation demonstrated that transmission
      latencies of most spikes remained inferior to 2 ms, like the NR group. These
      results indicate that synchrony of neural activity may be preserved in adult
      visual cortex despite abnormal postnatal visual experience. According to the
      temporal binding hypothesis, this also indicates that the necessary timing for
      visual perception is present despite anatomical abnormalities in visual cortex.

PMID- 20036841
TI  - Structure and function of archaeal prefoldin, a co-chaperone of group II
      chaperonin.
AB  - Molecular chaperones are key cellular components involved in the maintenance of
      protein homeostasis and other unrelated functions. Prefoldin is a chaperone that
      acts as a co-factor of group II chaperonins in eukaryotes and archaea. It assists
      proper folding of protein by capturing nonnative proteins and delivering it to
      the group II chaperonin. Eukaryotic prefoldin is a multiple subunit complex
      composed of six different polypeptide chains. Archaeal prefoldin, on the other
      hand, is a heterohexameric complex composed of two alpha and four beta subunits,
      and forms a double beta barrel assembly with six long coiled coils protruding
      from it like a jellyfish with six tentacles. Based on the structural information
      of the archaeal prefoldin, substrate recognition and prefoldin-chaperonin binding
      mechanisms have been investigated. In this paper, we review a series of studies
      on the molecular mechanisms of archaeal PFD function. Particular emphasis will be
      placed on the molecular structures revealed by X-ray crystallography and
      molecular dynamics induced by binding to nonnative protein substrates.

PMID- 20036843
TI  - TGF-beta signaling in alcohol induced hepatic injury.
AB  - Chronic alcohol consumption is a risk factor for the development of chronic liver
      disease. Ethanol exerts its detrimental effects by various means: Directly via
      toxic metabolites, and indirectly by affecting the gut barrier leading to
      elevated levels of endotoxins in the blood challenging the liver. These factors,
      together with the resulting inflammatory and profibrogenic cytokine production,
      drive the organ's response, characterized by activation of hepatic stellate
      cells. Recent evidence argues for other cell types besides hepatic stellate
      cells, including hepatocytes, as additional sources of fibroblasts producing
      extracellular matrix and to be responsible for scar formation. Besides mediating
      hepatocyte apoptosis, TGF-beta additionally induces fibroblastoid
      transdifferentiation. This process is accompanied with loss of epithelial marker
      proteins and upregulation of fibrosis related proteins. These findings challenge
      the current view of the passive role of hepatocytes in liver fibrosis. In line,
      hepatocyte-specific inhibition of the TGF-beta pathway prevents CCl4 induced
      liver injury. Hence, this review focuses on the interplay of TGF-beta and alcohol
      in chronic liver disease with special emphasis on the potential contribution of
      hepatocytes.

PMID- 20036842
TI  - Aging and the control of human skin blood flow.
AB  - Human exposure to cold and heat stimulates cutaneous vasoconstriction and
      vasodilation via distinct sympathetic reflex and locally mediated pathways. The
      mechanisms mediating cutaneous vasoconstriction and vasodilation are impaired
      with primary aging, rendering the aged more vulnerable to hypothermia and
      cardiovascular complications from heat-related illness, respectively. This paper
      highlights recent findings discussing how age-related decrements in sympathetic
      neurotransmission contribute directly to thermoregulatory impairments, whereas
      changes in local intracellular signaling suggest a more generalized age
      associated vascular dysfunction.

PMID- 20036844
TI  - Mechanisms of airway smooth muscle relaxation induced by beta2-adrenergic
      agonists.
AB  - Airway smooth muscle cell (ASMC) contraction is regulated by myosin
      phosphorylation to control actin-myosin cross-bridge activity. Myosin
      phosphorylation is determined by the antagonistic activity of myosin light chain
      (MLC) kinase (MLCK) and phosphatase (MLCP). MLCK activity is increased by
      increases in intracellular Ca2+ concentration ([Ca2+]i) associated with Ca2+
      oscillations. MLCP activity is decreased by phosphorylation of MLCP or accessory
      proteins by kinases, including Rho-kinase or protein kinase C. During agonist
      induced ASMC contraction, these 2 pathways are simultaneously activated. Because
      MLCP activity is often independent of [Ca2+]i, changes in MLCP activity can alter
      ASMC tone at a constant [Ca2+]i; a behavior termed Ca2+ sensitivity. In asthma,
      airway hyperresponsiveness (AHR) may result from an increase in the Ca2+
      dependent contractile mechanisms and/or the Ca2+ sensitivity of ASMCs.
      Conversely, inhalation of beta2-adrenergic agonists induce airway relaxation by
      simultaneously slowing the Ca2+ oscillations and reducing the Ca2+ sensitivity of
      ASMCs. However, the action of beta2-adrenergic agonists varies with species.
      Consequently, the development of beta2-adrenergic agonists requires a
      characterization of their action in human airways.

PMID- 20036845
TI  - Thermal comfort: research and practice.
AB  - Thermal comfort--the state of mind, which expresses satisfaction with the thermal
      environment--is an important aspect of the building design process as modern man
      spends most of the day indoors. This paper reviews the developments in indoor
      thermal comfort research and practice since the second half of the 1990s, and
      groups these developments around two main themes; (i) thermal comfort models and
      standards, and (ii) advances in computerization. Within the first theme, the PMV
      model (Predicted Mean Vote), created by Fanger in the late 1960s is discussed in
      the light of the emergence of models of adaptive thermal comfort. The adaptive
      models are based on adaptive opportunities of occupants and are related to
      options of personal control of the indoor climate and psychology and performance.
      Both models have been considered in the latest round of thermal comfort standard
      revisions. The second theme focuses on the ever increasing role played by
      computerization in thermal comfort research and practice, including sophisticated
      multi-segmental modeling and building performance simulation, transient thermal
      conditions and interactions, thermal manikins.

PMID- 20036846
TI  - Importance of glucocorticoid receptors in upper and lower airways.
AB  - Glucocorticoids (GCs) are the most common and effective drugs for treating
      inflammatory airway diseases, but some patients respond poorly to them. GC
      effects are mediated through the glucocorticoid receptor (GR). We present an
      update on the GR gene, the GR alpha and GR beta splicing variants, their
      translational and post-translational modifications, as well as their alterations
      in disease. GR alpha is ubiquitously expressed and is responsible for the
      induction and repression of target genes. GR beta acts as a dominant negative
      inhibitor of GR alpha-mediated transactivation and transrepression in certain
      cell types. The GR beta message is expressed at low levels in numerous tissues
      and its protein is only expressed in specific cell types. Increased GR beta
      expression has been reported in bronchial asthma, nasal polyposis and
      inflammatory bowel diseases (IBD), and after incubation of cells with certain
      proinflammatory stimuli. In addition to GR beta, other mechanisms explaining GC
      resistance include alterations in GR binding to ligand, nuclear translocation,
      and binding to GRE, and/or a defective cross-talk with transcription factors and
      cofactors.

PMID- 20036847
TI  - Molecular interactions in extracellular matrix of tendon.
AB  - Tendon is a poorly vascularized and highly specialized connective tissue
      containing few scattered cells that play an important role in the musculoskeletal
      apparatus by resisting mechanical stress. Because of the slow rate of the
      metabolism of its molecular components, the tendon gradually loses its mechanical
      properties and may rupture upon an array of physical activities. In this report,
      we discuss the molecular changes involved in the extracellular matrix-tendon
      interactions leading to tissue degeneration and rupture.

PMID- 20036848
TI  - "CXCR4-CXCL12 and VEGF correlate to uveal melanoma progression".
AB  - Despite improvements in early diagnosis of uveal melanoma, prognosis is still
      poor due to metastases development. Neoangiogenesis and migration are requisites
      to metastasis promotion. Cross-talking between CXCR4-CXCL12 axis and the VEGF
      pathway was shown to favours tumour progression. CXCR4-CXCL12-VEGF expression was
      evaluated by immunohistochemistry in 53 selected cases of primary uveal melanoma
      and in liver melanoma metastases. CXCR4 protein was detected in 41.4 per cent
      cases, CXCL12 in 43.4 per cent cases and VEGF expression in 39.6 per cent cases.
      A significant correlation was found between CXCR4 and VEGF expression (p=0.011),
      CXCL12 and both tumour dimension and (p=0.006) and epithelioid-mixed cytotype
      (p=0.012). The two cases of uveal melanoma liver metastases in our series showed
      CXCR4 expression, weak immunoreactivity for CXCL12 and absent VEGF
      immunostaining. These data indicate that CXCR4-CXCL12 axis and its cross-talking
      with VEGF plays a role in uveal melanoma metastases and may be new prognostic
      markers in UMM. Moreover, these results suggest that targeted inhibition of CXCR4
      could be introduced to control metastasis development in UMM.

PMID- 20036849
TI  - Transcriptional regulation of the presenilin-1 gene controls gamma-secretase
      activity.
AB  - Inhibition of basal JNK activity by JNK inhibitor SP600125 or JNK1siRNA repressed
      presenilin-1 (PS1) expression in SK-N-SH cells by augmenting the level of p53, a
      repressor of the PS1 gene (1). We now showed that repression of PS1 transcription
      by JNK inhibitor SP600125 inhibited gamma-secretase mediated processing of
      amyloid precursor protein (APP) resulting in the accumulation of C99 fragment and
      the reduction of secreted Abeta40 level without altering the expression of
      nicastrin (NCT). Co-treatment of cells with SP600125 and p53 inhibitor, pifithrin
      alpha, partially nullified the suppressive effects of SP610025 on PS1 expression
      and secreted Abeta40 level. Suppression of JNK1 by JNK1siRNA also decreased
      Abeta40 level. Furthermore, overexpression of the repressors p53, ZNF237 and CHD3
      of the PS1 gene also suppressed the processing of APP through repression of PS1
      transcription by deacetylation of histone at the PS1 promoter. Transcriptional
      activator Ets2 increased PS1 protein and secreted Abeta40 levels without
      affecting the expression of NCT by activating PS1 transcription via hyper
      acetylation of histone at the PS1 promoter. Therefore, regulation of PS1
      transcription modulates gamma-secretase activity.

PMID- 20036850
TI  - Activin A in asphyxiated full-term newborns with hypoxic ischemic encephalopathy.
AB  - Activin-A is a protein over-expressed and secreted by the brain after neuronal
      destruction. We evaluated whether serum activin-A increases in asphyxiated full
      term newborns (AFTNs) at risk of hypoxic-ischemic-encephalopathy (HIE). 105
      consecutive infants (35 affected by perinatal asphyxia due to acute fetal
      distress; 70 healthy gestational-age matched newborns) underwent cranial
      assessment and neurologic examination at 12, 24 and 72 hours after birth and, on
      discharge from the hospital and; activin-A and monitoring laboratory variables
      assessment at birth. According to the occurrence of HIE within 7-days after
      birth, AFTNs were subdivided in Group A (n= 20; no/mild HIE with good prognosis)
      and Group B (n= 15; moderate/severe HIE with a greater risk of neurological
      handicap). Activin-A was significantly (P less than 0.0001) higher in Groups A
      and B than controls and highest (P less than 0.001) in Group B. At 0.66 ng/L
      activin-A achieved a sensitivity of 93.33 per cent and a specificity of 96.63 per
      cent, respectively, as HIE diagnostic test. These findings show that activin A
      increased in AFTNs with HIE before the appearance of related signs.

PMID- 20036851
TI  - Maternal stress-induced reduction in birth weight as a marker for adult affective
      state.
AB  - It is known that adverse events experienced by a pregnant woman may be reflected
      upon the developing fetus and adversely affect its mental wellbeing in later
      life. In a recent study by our group, prenatal stress was associated with a clear
      increase in anxiety- and depression-related behavior in male, but not female
      Sprague-Dawley offspring. Since birth weight data were recorded we were able to
      determine whether birth weight, as an important outcome measure of fetal
      distress, may be used as a predictive indicator for adult performance. For this
      purpose, a correlation analysis was performed, aimed at studying the possible
      link between stress-induced fetal growth restriction and adult affective state.
      Male birth weight correlated positively to depression-related behavior in the
      forced swim test. Furthermore, it weight was correlated negatively to basal, and
      positively to stress-induced, plasma corticosterone levels in adulthood. Female
      birth weight did not correlate to any of the studied outcome measures. These data
      suggest that male birth weight may represent a valuable indicative marker for
      variations in adult affective state with a developmental origin.

PMID- 20036852
TI  - S100 beta protein is increased in fetuses with neural tube defect.
AB  - We investigated the levels of S100 beta protein (S100B) in the serum of fetuses
      with neural tube defects (NTD), and their mother. Samples from 20 fetuses with
      NTD and 30 controls at the same gestational age, and their mothers, were studied.
      S100B protein levels were determined using Lia-mat Sangtec. kit. S100B
      concentrations were significantly higher in NTD fetuses (median 2.71 microg/L)
      than in control subjects (median 0.98 microg/L). Increased S100B levels were also
      found in mothers carrying fetuses with NTD compared to control and uncomplicated
      pregnancies. This study indicates that NTD is associated with increased serum
      concentration of S100B in fetuses and mothers. Moreover, it gives information on
      S100B levels in the fetal circulation in early-mid gestation.

PMID- 20036853
TI  - Changes in the interrelationship between leptin, resistin and adiponectin in
      early neonatal life.
AB  - The aim of this study was to investigate the interrelationship between
      leptin,adiponectin and resistin in the fetal and early postnatal period and the
      association of these hormones with anthropometric and metabolic indexes. Serum
      concentrations of leptin, adiponectin and resistin were measured in maternal and
      neonatal circulation at delivery and on the 3rd day after birth in 40 healthy
      newborns and their mothers Serum leptin levels were significantly higher in
      fetuses that in newborn infants on 3rd day after delivery, whereas concentration
      of adiponectin and resistin were maintained in either maternal and neonatal
      circulation after delivery. Leptin serum concentrations correlated with those of
      adiponectin in the fetal circulation, but not in neonatal life. On the other hand
      no correlation was found between leptin and resistin levels in cord blood,
      whereas a positive correlation between leptin and resistin concentrations was
      present in the neonatal circulation on 3rd day. Fetal leptin, adiponectin and
      resistin levels are largely independent of maternal influences and immediately
      after birth, important changes in the relation among adipokines occurred compared
      to intrauterine life.

PMID- 20036854
TI  - The relation of S100beta and metabolic and endocrine responses to acute fetal
      hypoxemia.
AB  - Elevations in S100beta protein in umbilical cord blood have been proposed as a
      reproducible marker of fetal stress, leading to cell damage within the central
      nervous system. However, it remains unknown whether fetal S100beta concentrations
      correlate with established endocrine and metabolic indices of fetal distress.
      Hence, in the late gestation ovine fetus, plasma concentrations of S100beta,
      adrenocorticotropic hormone (ACTH), cortisol, neuropeptide Y (NPY), and
      catecholamines and blood concentrations of glucose and lactate were measured
      during acute hypoxemia. Under general anesthesia, 5 sheep fetuses were
      chronically instrumented with catheters and subjected 5 days later to 1h
      normoxia, 0.5h hypoxemia and 1h recovery. Plasma samples were taken during each
      experimental period. Hypoxemia induced significant falls in PaO2 with increases
      in fetal plasma concentrations of ACTH, cortisol, catecholamines and NPY, and
      elevations in blood glucose and lactate, all of which showed significant positive
      relationships with fetal plasma S100beta concentrations. Hence, evaluation of
      S100beta may provide a valuable clinical tool in the assessment of fetal well
      being in suspected complicated pregnancies.

PMID- 20036855
TI  - MUC1 expression by human airway epithelial cells mediates Pseudomonas aeruginosa
      adhesion.
AB  - Human MUC1 (Muc1 in animals) is an extensively O-glycosylated membrane-tethered
      mucin expressed on the surface of epithelial cells and some cells of the
      hematopoietic system. Recently, we showed that the hamster Muc1 on Chinese
      hamster ovary (CHO) cells served as a binding site for Pseudomonas aeruginosa
      (PA) through interaction between bacterial flagellin and the Muc1 ectodomain.
      Because CHO cells are known to produce an atypical pattern of protein
      glycosylation, we determined whether or not PA interacted with MUC1 endogenously
      expressed on human airway epithelial cells. Knock down of MUC1 expression in
      bronchial (NuLi-1) or alveolar (A549) epithelial cells by RNA interference
      significantly reduced PA binding to the cells. Conversely, over-expression of
      MUC1 in HEK293 cells increased bacterial adherence. By confocal microscopy, PA
      and MUC1 were colocalized on the surface of NuLi-1 cells. Taken together, these
      results confirm our previous observations in CHO cells and suggest that MUC1
      serves as a binding site for PA on the surface of airway epithelial cells, which
      may have important consequences in the pathogenesis of PA lung infections.

PMID- 20036856
TI  - Electronegative LDL induces Fas and modifies gene expression in mononuclear
      cells.
AB  - Electronegative LDL (LDL(-)) is a minor modified LDL subfraction that promotes
      cytokine release by human mononuclear cells. The aim of the current study was to
      evaluate changes in gene expression induced by LDL(-) versus native LDL in
      lymphocytes and monocytes. Therefore, mononuclear cells were incubated with these
      LDL subfractions and their effects on expression in human whole genome were
      analyzed by gene array. Differential expression of the genes was quantified by
      real-time RT-PCR. LDL(-) altered the gene expression pattern, particularly of
      inflammatory genes. LDL(-) down-regulated CD36 and colony-stimulating factor 1
      receptor (CSF1R) genes and up-regulated Fas expression and Fas protein on
      cellular membrane. LDL(-) seemed to promote the alterations in these genes by
      activation of NF-kB and inhibition of AP1 and PPARG. In conclusion, LDL(-)
      induced changes in gene expression in monocytes and lymphocytes. Fas up
      regulation suggests a proinflammatory action; however, CSF1R and CD36 down
      regulation could decrease monocyte differentiation and activation. Therefore,
      LDL(-) promoted not only inflammatory effects but also counteracting actions in
      circulating mononuclear cells.

PMID- 20036857
TI  - Trans-10,cis-12-CLA dysregulate lipid and glucose metabolism and induce hepatic
      NR4A receptors.
AB  - Our aim was to assess the effect of two isomers of conjugated linoleic acids
      (CLA), cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12-CLA), on
      glucose metabolism and hepatic expression of NR4A receptors, key transcription
      factors regulating gluconeogenesis. ApoE-deficient mice were fed isocaloric,
      isonitrogenous westernized diets enriched with c9,t11-CLA, t10,c12-CLA or
      linoleic acid (control diet). Plasma glucose, NEFA, triglyceride and cholesterol
      concentrations were significantly higher in the t10,c12-CLA group compared with
      c9,t11-CLA or control group. Plasma insulin concentrations were lowered by c9,t11
      CLA compared with either control or t10,c12-CLA group. Hepatic expression of NR4A
      receptors (Nur77, Nurr1 and NOR-1) was induced by t10,c12-CLA while c9,t11-CLA
      had not effect. Consistently t10,c12-CLA up-regulated key genes involved in
      gluconeogenesis including glucose-6-phosphatase, enolase, phosphoenolpyruvate
      carboxykinase and pyruvate carboxylase. Hepatic expression of NR4A receptors
      correlated with plasma NEFA, with the expression of their target gene fatty acid
      transporter (FAT)/CD36 and with the accumulation of fat in the liver. These
      results suggest that t10,c12-CLA promote dysregulation of lipid and glucose
      metabolism, at least in part, by an isomer-specific modulation of hepatic
      expression of NR4A receptors.

PMID- 20036858
TI  - Influence of obesity, physical inactivity, and weight cycling on chronic
      inflammation.
AB  - Obesity prevalence continues to rise due to excessive caloric intake and
      sedentary behavior. Weight loss can be achieved through diet and/or exercise, but
      maintenance of a reduced weight is rare and relapse is prevalent. Repeated
      periods of weight loss and regain have been termed "weight cycling." It has been
      speculated that weight cycling may further increase the elevated disease risk
      common with weight gain, obesity, and physical inactivity. Alterations in adipose
      tissue with weight cycling may create a more hypoxic environment; hypoxic adipose
      tissue secretes leptin, a stimulus for macrophage activation and accumulation
      within adipose tissue. Hypoxic adipocytes and macrophages release pro
      inflammatory cytokines into circulation. Elevated body weight and adiposity are
      linked to cardiovascular disease and type 2 diabetes via an inflammatory
      mechanism. Thus, it is reasonable to speculate that weight cycling causes a more
      profound change in chronic inflammation than sustained weight gain. The purpose
      of this review is to explore inflammatory consequences associated with weight
      cycling as they are related to sustained weight gain, obesity, physical
      inactivity as well as relative disease risk.

PMID- 20036859
TI  - Biochemical characteristics and risk factors in non-alcoholic fatty liver.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a condition associated with
      metabolic disturbances. The aim of the present study was to investigate the
      biochemical characteristics and risk factors for NAFLD. The study was carried out
      in a total of 881 subjects diagnosed by ultrasonography. NAFLD occurred mainly in
      middle-aged individuals, with a prevalence of 63.1 per cent. Multiple logistic
      regression analysis showed that male gender, presence of obesity, hypertension,
      dyslipidemia, or Type 2 diabetes and elevated serum alanine transaminase
      activities were independent risk factors for the development of NAFLD. Subjects
      with NAFLD were obese, hypertensive and often had signs of disturbances in lipid
      and glucose metabolism and abnormalities in hepatic functions. These findings
      show risk factors in the development and offer opportunities for prevention of
      NAFLD.

PMID- 20036860
TI  - Enhanced external counterpulsation is a regenerative therapy.
AB  - Enhanced external counterpulsation (EECP) is used for the treatment of severe
      angina and heart failure in patients who are not candidates for
      revascularization. The clinical benefits of EECP extend well beyond the time
      period of any hemodynamic effects, but the cause of this prolonged effect is not
      understood. The prolonged clinical benefits suggest EECP could be a regenerative
      therapy. This study was performed to determine whether EECP increased circulating
      hematopoietic progenitor cells (HPCs) or endothelial progenitor cells (EPCs) and
      thus be a possible regenerative therapy. The proposed mechanism of the increase
      in regenerative circulating stem cells is the enhanced shear forces induced on
      the endothelial boundary by the flow reversal produced by the sequential
      inflation of the pneumatic cuffs during EECP therapy.

PMID- 20036861
TI  - A review of autoimmune diseases associated with cancer.
AB  - The focus of this review is on the relationships between autoimmune diseases and
      cancer from two closely related perspectives: 1.Those autoimmune diseases which
      are often associated with malignancies. 2.Those prevalent cancers which may
      increase the risks of developing autoimmune disorders. The review concludes with
      a brief discussion of some selected innovative approaches to cancer
      immunotherapy.

PMID- 20036862
TI  - Mouse microRNA-124 regulates the expression of Hes1 in P19 cells.
AB  - MicroRNAs (miRNAs) belong to a conserved class of small non-coding RNAs that are
      typically 18-25 nucleotides long. They are found in both animals and plants.
      These small RNAs can regulate gene expression at translational level by
      interacting with their target messenger RNAs, and they play an essential role in
      the development of plants and animals. To date, more than 200 miRNAs have been
      identified in mammals; however, their mRNA targets have not yet been identified.
      In this study, we demonstrate that the expression of Hes-1, which is a basic
      helix-loop-helix transcriptional repressor, is regulated by miRNA-124 in P19
      cells. Reduction in the levels of miR-124 mediated by locked nucleic acids
      resulted in the accumulation of Hes-1 and hindered the retinoic acid-induced
      neuronal differentiation of P19 cells. Thus, our results indicate that miR-124
      regulates the expression of Hes-1 at the post-transcriptional level and is
      involved in the retinoic acid-induced neuronal differentiation of P19 cells.

PMID- 20036863
TI  - Ochratoxin A induces craniofacial malformation in mice acting on Dlx5 gene
      expression.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by fungal of Aspergillus species
      absorbed in human through contaminate food in gastrointestinal tract. OTA has
      been demonstrated to be teratogenic in a number of species including mice and
      potentially human. Mice exposed in uterus to OTA develop craniofacial
      abnormalities such as exencephaly, microencephaly, microphthalmia and facial
      clefts. An important role in differentiation of maxillofacial are exerted by the
      Hox related genes Dlx and Msx. In the present investigation we have confirmed
      that 2.75 mg/kg body weight OTA, given at gestational day 7.5, induces
      significant developmental craniofacial anomalies in mice and we have demonstrated
      the down expression of Dlx5, a member of Dlx gene family, that seems to be
      responsible of the observed deformities. These results support the hypothesis
      that Dlx5 is a target for ochratoxin and the inhibition of its function, directly
      or indirectly, could be at origin of the observed differentiation defects.

PMID- 20036864
TI  - HBV X protein interacts with cytoskeletal signaling proteins through SH3 binding.
AB  - The aim of this study was to investigate interactions between cellular SH3
      containing proteins and the proline-rich domain in Hepatitis B Virus (HBV) X
      protein (HBx) The proline-rich domain of HBx (amino acids 19-58) as well as the
      relevant site-directed mutagenesis (proline to alanine residues) were cloned into
      pGEX-5X-1 and expressed as GST-PXXP and GST-AXXA probes. Panomics SH3 domain
      arrays were probed using both GST-PXXP and GST-AXXA to identify potential
      interacting SH3 domain containing proteins. The specific interactions were
      confirmed by the immunoprecipitation of the full-length SH3 domain-containing
      protein. We report here the binding assay which demonstrated interaction between
      PXXP domain in HBx and the SH3-domain containing proteins, in particular various
      signaling proteins involved in cytoskeletal reorganization. Our findings were
      consistent with similar virus-host interactions via SH3 binding for other viruses
      such as hepatitis C virus (HCV) and human immunodeficiency virus (HIV) Further
      characterization of the proline-rich binding to SH3 domains could yield important
      information for the design of novel therapeutic measures against downstream
      disease causative effects of HBx in the liver cells.

PMID- 20036865
TI  - Simultaneous determination of mycotoxins in biological fluids by LC-MS/MS.
AB  - We report a single, reliable, non-invasive analytical method for monitoring the
      fetal level of exposure to different mycotoxins. We assessed by tandem mass
      spectrometry levels up to 200 nanog/l for ochratoxin A and 500 nanog/l for
      aflatoxins in sample of serum (n= 71), urine (n= 18) and amniotic fluid (n= 21)
      of pregnant women. Aflatoxin G1 was present in one sample of serum (3.48
      microg/l) and in four samples of urine (ranging from 14.0 to 18.8 microg/l),
      ochratoxin A was present in one sample of amniotic fluid (4.26 microg/l), whereas
      aflatoxin B1 (ranging from 0.4-2 microg/l) and B2 (ranging from 0.3-3 microg/l)
      were contextually present in two samples of urine. The very few contaminated
      samples did not allow statistical comparison between subjects grouped according
      to the frequency of consumption of commonly contaminated foods. Data confirm that
      mycotoxins can occur in fetal-maternal biological fluids. However, the incidence
      and the level of exposure to the investigated mycotoxins do not appear to pose
      risk for the mother and the fetus.

PMID- 20036866
TI  - S100B protein and near infrared spectroscopy in preterm and term newborns.
AB  - Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near
      Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants
      although data in healthy infants are lacking. The present study investigates
      whether NIRS parameters change according to gestational age and correlate with
      S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in
      which we performed in the first 6-hours after birth routine clinical,
      radiological and laboratory variables, cerebral oxygen saturation (rSO2),
      fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine
      assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for
      both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than
      0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased
      and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39
      weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77;
      FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that
      NIRS parameters and S100B protein correlation may be of help in brain function
      monitoring.

PMID- 20036867
TI  - Acrylamide disturbs genomic imprinting during spermatogenesis.
AB  - Acrylamide (ACR), a carcinogen for rodents and humans, exists widely in the human
      living environment and heat-treated carbohydrate foodstuffs. Increasing evidence
      has demonstrated that ACR can cause chromosomal damage in somatic cells and
      mutagenesis. However, little is known about whether ACR can disturb genomic
      imprinting during spermatogenesis. We investigated the effects of ACR on
      methylation patterns of rat sperm genes. The results showed that after oral
      administration of ACR to rats for two weeks, methylation of some cytosines in the
      CpG islands of the differentially methylated region (DMR2) of sperm gene insulin
      like growth factor II (Igf2), which is still present at the 19th day, disappeared
      on the 35th day. Furthermore, the extent by which ACR causes methylation defects
      varies in animals. Our findings indicate that mitotic spermatogonia and primary
      spermatocytes are sensitive to ACR-induced genomic imprinting aberration,
      suggesting that ACR predominantly interferes with the remodeling process in
      spermatogenesis.

PMID- 20036868
TI  - Cross phenotype normalization of microarray data.
AB  - Normalization is a prerequisite for almost all follow-up steps in microarray data
      analysis. Accurate normalization across different experiments and phenotypes
      assures a common base for comparative yet quantitative studies using gene
      expression data. In this paper, we report a comparison study of four
      normalization approaches, namely, linear regression (LR), Loess regression,
      invariant ranking (IR) and iterative nonlinear regression (INR), for gene
      expression data normalization. Among these four methods, LR and Loess regression
      methods use all available genes to estimate either a linear or nonlinear
      normalization function, while IR and INR methods feature some iterative processes
      to identify invariantly expressed genes (IEGs) for nonlinear normalization. We
      tested these normalization approaches on three real microarray data sets and
      evaluated their performances in terms of variance reduction and fold-change
      preservation. By comparison, we found that (1) LR method exhibited the worst
      performance in both variance reduction and fold-change preservation, and (2) INR
      method showed an improved performance in achieving low expression variance across
      replicates and excellent fold-change preservation for differentially expressed
      genes.

PMID- 20036869
TI  - LM23 is essential for spermatogenesis in Rattus norvegicus.
AB  - LM23 is a gene with testis-specific expression in Rattus norvegicus. To reveal
      the function of LM23 in the testis, we used lentivirus-mediated RNA interference
      (RNAi) to knock down LM23 expression in a tissue-specific manner in vivo. A
      lentiviral vector expressing a short hairpin RNA (shRNA) targeting LM23 was
      microinjected into the efferent ducts of R. norvegicus testes. The expression of
      LM23 in the treated testes was significantly knocked down compared with controls.
      These LM23-shRNA testes contained germ cells arrested at the spermatocyte stage,
      and showed increased apoptosis and disregulation of some meiotic genes. The
      results demonstrate the validity of the RNAi approach for targeting LM23 and
      reveal that LM23 expression in the testis is crucial for meiosis during
      spermatogenesis in R. norvegicus.

PMID- 20036870
TI  - A novel dihydroimidazoline, trans-Pro mimetic analog is a selective PK/PBAN
      agonist.
AB  - The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family
      plays a significant role in the regulation of reproductive and developmental
      processes in a variety of insects. A transPro, type I beta-turn has been
      previously identified as important for the activity of PK/PBAN peptides. A
      PK/PBAN analog (PPK-Jo) incorporating a novel dihydroimidazole transPro mimetic
      motif was evaluated in four PK/PBAN bioassays (pheromonotropic, melanotropic,
      pupariation and hindgut myotropic). PPK-Jo proved to be a pure, selective
      melanotropic agonist in S. littoralis. The melanotropic receptor in S. littoralis
      demonstrates more tolerance to deviations from the ideal transPro structure than
      those of other PK/PBAN assays. The selective PK/PBAN agonist represents a new
      tool to better understand the endogenous mechanisms of these peptides and serves
      as a probe of the plasticity of PK/PBAN regulated systems and receptors. The
      dihydroimidazoline moiety is shown to function as a surrogate for a transPro in
      certain circumstances, and provides a novel scaffold with which to construct
      mimetic PK/PBAN analogs with enhanced selectivity and the potential to disrupt
      critical physiological processes in insect pests.

PMID- 20036871
TI  - Correlation of the virulence of CSFV with evolutionary patterns of E2
      glycoprotein.
AB  - Infection with classical swine fever virus (CSFV) is costly to the livestock
      industry. Several genomic sequences including velogenic strains and low virulent
      strains have been identified. However, the reasons for the virulence of the virus
      have remained unclear. Based on selective pattern and pressure strength, we
      classified all genes of CSFV into three classes. Among these genes, the E2 gene
      was under the strongest positive selection. Based on the analysis of 85
      representative E2 gene sequences, the location and intensity of positive
      selection in CSFV isolates from group one and group two were identified. These
      results suggest that these two groups employ evolutionary difference. Moreover,
      the mutations, potentially driven by positive selection, can be correlated with
      the virulence of CSFV by altering the conformation and function of E2 and/or
      changing its glycosylation pattern. Based on these results, a model for the
      evolution of virulence of CSFV is proposed. The results provide a link between
      epidemiology and the gene function of CSFV, and may shed light on the molecular
      mechanism underlying the variation of CSFV virulence.

PMID- 20036872
TI  - Bing De Ling, a Chinese herbal formula, inhibits cancer cells growth via p53.
AB  - Bing De Ling is a Chinese herbal formula that has been used to treat cancer
      patients for more than a decade. However, the molecular mechanisms behind its
      anti-tumor efficacy are still elusive. Here, we show that Bing De Ling inhibits
      cell proliferation in ovarian cancer epithelial cell lines, OV2008 and C13. It
      induces G1/S arrest in a p53-dependent manner in that this effect is attenuated
      in OV2008 cells transfected with dominant-negative p53 plasmid. Moreover, we show
      that Bing De Ling up-regulates p53 transcriptional activities as well as its
      downstream target genes, such as p21Cip1, MDM2, and MDMX. In addition, Bing De
      Ling inhibits MDMX-p53 interaction which may result in stabilization and
      activation of p53. Collectively, our results suggest that the anti-tumor activity
      of Bing De Ling may be in part due to activation of p53.

PMID- 20036873
TI  - PE-CMOS based C-scan ultrasound for foreign object detection in soft tissue.
AB  - In this paper, we introduce a C-scan ultrasound prototype and three imaging
      modalities for the detection of foreign objects inserted in porcine soft tissue.
      The object materials include bamboo, plastics, glass and aluminum alloys. The
      images of foreign objects were acquired using the C-scan ultrasound, a portable B
      scan ultrasound, film-based radiography, and computerized radiography. The C-scan
      ultrasound consists of a plane wave transducer, a compound acoustic lens system,
      and a newly developed ultrasound sensor array based on the complementary metal
      oxide semiconductor coated with piezoelectric material (PE-CMOS). The contrast-to
      noise ratio (CNR) of the images were analyzed to quantitatively evaluate the
      detectability using different imaging modalities. The experimental results
      indicate that the C-scan prototype has better CNR values in 4 out of 7 objects
      than other modalities. Specifically, the C-scan prototype provides more detail
      information of the soft tissues without the speckle artifacts that are commonly
      seen with conventional B-scan ultrasound, and has the same orientation as the
      standard radiographs but without ionizing radiation.

PMID- 20036874
TI  - Comparison of methods for evaluating drug-drug interaction.
AB  - The goal of the present report is to compare several published methods of
      analyzing drug-drug interaction data. The compared methods are the curve-shift
      analysis, isobologram, combination index, and universal surface response
      analysis, and the comparison was based on analysis of published cytotoxicity data
      of combinations of two anti-folate agents. Major findings are as follows. The
      curve shift analysis enabled the inspection of the experimental data and visual
      evaluation of the approximate parallelism between the dose response curves.
      Isobologram analysis provided the range of concentration ratios where maximal
      synergy was obtained. The combination index analysis readily provided
      quantitative estimation of the extent of synergy or antagonism. The universal
      surface response method summarized drug-drug interaction in a single parameter,
      facilitating comparison of larger arrays of combinations. Only the curve shift
      analysis and the universal surface response method yielded a statistical estimate
      of differentiation between synergy, additivity, and antagonism. In summary, curve
      shift analysis, isobolograms, combination index analysis, and the universal
      response surface method are useful methods for analyzing drug-drug interaction,
      and provide complementary information.

PMID- 20036875
TI  - Comparison of methods for statistical analysis of combination studies.
AB  - This paper is concerned with the statistical analysis of data obtained in studies
      of the joint action of drugs. The three methods that are compared are illustrated
      on real data (1), using the statistical package SAS. It is argued that while the
      results obtained using these methods do not differ substantially, the method
      allowing for estimating simultaneously all required parameters is to be
      preferred. It allows for a statistical test for the significance of the joint
      action of the drug combinations to be carried out.

PMID- 20036876
TI  - Efficient experimental design and nonparametric modeling of drug interaction.
AB  - The design and analysis of drug combination studies continue to be an area
      requiring further methodological developments. Faessel et al. (1998) studied the
      joint effects of the combinations of trimetrexate (TMQ) and the GARFT inhibitor
      AG2034 to inhibit the growth of HCT-8 human ileocecal adenocarcinoma cells. Their
      experiments provide a rich data resource to validate the performance of new
      experimental design and analysis methods for future experiments. In this paper,
      we first re-analyze the same data with a nonparametric model and briefly review
      the experimental design used in the original paper. By comparing the analysis
      results, we found that the fixed ratio design and the usage of the parametric
      model for estimating the interaction index are based on an assumption not
      supported by the data. We then show how the efficiency of the experiments would
      be improved had the maximal power experimental design based on uniform measures
      been used. The usage of the proposed maximal power experimental design is further
      supported by simulation studies.

PMID- 20036877
TI  - Application and review of the separate ray model to investigate interaction
      effects.
AB  - In this paper we review the application of the Separate Ray Model to analyze drug
      combination experiments coming from a fixed ratio design. The idea is the joint
      fit of separate concentration response curves to each ray under investigation
      leading to an interaction index for each together with a 95 percent Confidence
      Interval. The approach is a simple and easy to implement parametric modeling
      approach and allows estimation and testing of drug interactions based on
      regularly sampling in the entire space of all combinations going from pure
      compound A to pure compound B. The analysis is implemented using the SAS/STAT
      procedure NLMIXED. Two datasets were provided for the modeling exercise. One
      included different qualitative effects with some rays showing synergy, others
      antagonism and again others additivity. The second dataset involved the presence
      of very large synergy together with different observed background effects for the
      individual rays. The Separate Ray Model is able to handle these practical issues
      making it a flexible tool to investigate drug interaction experiments using a
      fixed ratio design.

PMID- 20036878
TI  - Applying Emax model and bivariate thin plate splines to assess drug interactions.
AB  - We review the semiparametric approach previously proposed by Kong and Lee and
      extend it to a case in which the dose-effect curves follow the Emax model instead
      of the median effect equation. When the maximum effects for the investigated
      drugs are different, we provide a procedure to obtain the additive effect based
      on the Loewe additivity model. Then, we apply a bivariate thin plate spline
      approach to estimate the effect beyond additivity along with its 95 per cent
      point-wise confidence interval as well as its 95 per cent simultaneous confidence
      interval for any combination dose. Thus, synergy, additivity, and antagonism can
      be identified. The advantages of the method are that it provides an overall
      assessment of the combination effect on the entire two-dimensional dose space
      spanned by the experimental doses, and it enables us to identify complex patterns
      of drug interaction in combination studies. In addition, this approach is robust
      to outliers. To illustrate this procedure, we analyzed data from two case
      studies.

PMID- 20036879
TI  - Response of the thermoregulatory system to toxic insults.
AB  - The physiological response to environmental toxicants and drugs is modulated by
      the thermoregulatory system. Environmental and body temperature can affect the
      entry of toxicants into the body through pulmonary, cutaneous, and
      gastrointestinal routes. Thermoregulation can ultimately influence the metabolic
      clearance of chemicals and their toxicity, including lethality. The
      thermoregulatory response following acute exposure to many toxic chemicals
      involves a regulated hypothermic response, characterized by activation of
      autonomic thermoeffectors to raise heat loss and a behavioral preference for
      cooler temperatures. Moderate hypothermia in rodents improves recovery and
      survival following toxic exposure. In relatively large mammals, including humans,
      the hypothermic response is minimal. Fever-like responses are often seen in
      humans and other large mammals exposed to many toxicants. Fever is also observed
      in rodents exposed to some toxicants provided that core temperature can be
      monitored without disturbing the animal (e.g., telemetry). Overall, the universal
      effects of temperature on chemical toxicity call for researchers to have a better
      understanding of how body and ambient temperature affect the physiological
      response to environmental toxicants.

PMID- 20036880
TI  - Ablation of iNOS delays cardiac contractile dysfunction in chronic hypertension.
AB  - We investigated the role of inducible NOS (iNOS) on cardiac function during the
      development of left ventricular hypertrophy. Hypertrophy was induced by pressure
      overload via short-term (2.5 months) or long-term (6.5 months) aortic banding
      (AoB) in wild-type (WT) and iNOS knock out (iNOSKO) mice. Cardiac function was
      then assessed via echocardiography, in situ hemodynamics and papillary muscle
      force measurements. Quantitative RT-PCR and Western blots were used to measure
      expression of hypertrophic gene markers and proteins respectively. Our data
      demonstrate that increased afterload via AoB leads to increased expression of
      iNOS that is associated with cardiac dysfunction. In pressure-overload induced
      hypertrophy, iNOSKO delays both the expression of hypertrophic markers and
      contractile dysfunction without causing significant changes in the level of
      hypertrophy. Moreover, after long-term AoB, iNOSKO animals exhibited increased
      basal cardiac function and an improved response to beta-adrenergic stimulation
      compared to long-term AoB WT animals. In conclusion, our data demonstrate that NO
      production via iNOS plays an important role in modulating cardiac function after
      moderate AoB that mimics long-term hypertension in humans.

PMID- 20036882
TI  - Multilayer CuHCF films bridged by CuMPCs for H2O2 detection.
AB  - Multilayer copper hexacyanoferrate (CuHCF) films bridged by cysteine monolayer
      protected copper clusters (CuMPCs) were prepared by the sequential
      electrochemical cyclcing and dipping process. Cyclic voltammetry, scanning
      electron microscopy (SEM) and atomic force microscopy (AFM) were used to
      characterize the formation of the multilayer films. Cyclic voltammetric
      measurements indicated that the films grew exponentially with the increase of the
      layer numbers. AFM and SEM images revealed that the obtained films were thin and
      exhibited a three-dimensional structure. The nanostructured thin-film assemblies
      exhibited interesting catalytic properties that could be applied in important
      sensing and catalysis. Good catalytic activity and stability of the film modified
      electrode for hydrogen peroxide detection was studied.

PMID- 20036881
TI  - Microarray probes and probe sets.
AB  - DNA microarrays have gained wide use in biomedical research by simultaneously
      monitoring the expression levels of a large number of genes. The successful
      implementation of DNA microarray technologies requires the development of methods
      and techniques for the fabrication of microarrays, the selection of probes to
      represent genes, the quantification of hybridization, and data analysis. In this
      paper, we concentrate on probes that are either spotted or synthesized on the
      glass slides through several aspects: sources of probes, the criteria for
      selecting probes, tools available for probe selections, and probes used in
      commercial microarray chips. We then provide a detailed review of one type of DNA
      microarray: Affymetrix GeneChips, discuss the need to re-annotate probes, review
      different methods for regrouping probes into probe sets, and compare various
      redefinitions through public available datasets.

PMID- 20036883
TI  - Effects of TGF beta-1 on mouse embryo implantation and expression of H2-D1 and H2
      DM.
AB  - We investigated the mechanism that TGF-beta1 influences the immuno-environment at
      maternal-fetal interface and affects embryo implantation, using mouse uterine
      horn injection model. The expression of MHC I antigen (H2-D1) and the chaperone
      of MHC II antigen (H2-DM) after anti-TGF-beta1 antibody or hrTGF-beta1 treated
      pregnant mice were examined by real-time PCR, western blotting and
      immunohistochemistry. The results showed that the number of implanted embryos of
      anti-TGF-beta1 antibody-treated mice was decreased compared with the control. The
      expression of H2-D1 and H2-DM on days 6 and 7 treated uteri was increased both at
      mRNA and protein levels. In hrTGF-beta1 treated group, the expression of H2-D1
      and H2-DM protein was decreased, and the number of implanted embryos was slightly
      increased. Immunohistochemical studies revealed that H2-D1 and H2-DM were mainly
      localized to the primary decidual zone. The anti-TGF-beta1 antibody and exogenous
      hrTGF-beta1 treatment altered the intensity of H2-D1 and H2-DM signal but did not
      change their localization. These observations suggested that injection of anti
      TGF-beta1 antibody affected the number of mouse embryo implantation, and
      regulated the expression of H2-DM and H2-Q10.

PMID- 20036884
TI  - Mitochondrial DNA damage analysis in bronchoalveolar lavage cells of preterm
      infants.
AB  - In mechanically ventilated preterm infants, the combination of immaturity,
      volutrauma, oxidative stress, and inflammatory processes can lead to chronic lung
      injury. Mitochondrial DNA (mtDNA) is more susceptible to oxidative damage than
      nuclear DNA. We aimed to investigate the level of mtDNA damage (deletions,
      mutations and changes in copy number) in bronchoalveolar lavage (BAL) cells from
      10 preterm infants (27-30 weeks). A first BAL (BAL1) was done within 24 h of
      endotracheal intubation and BAL2 was performed 30-103 h thereafter. Deletions
      were analyzed by long range PCR, point mutations by heteroduplex analysis of the
      D-loop region, and copy number changes by real-time PCR. Using these methods, no
      deletions were found in any of the BAL samples. When BAL1 and BAL2 samples were
      compared no new mutations were found. In contrast, a marked decrease in mtDNA
      copy number was observed in 5 patients. In conclusion, we found that exposure of
      preterm infants to short term mechanical ventilation did not lead to detrimental
      consequences for the mtDNA in the form of mutations or deletions.

PMID- 20036885
TI  - Age-related changes in isoprostane-mediated relaxation of piglet blood vessels.
AB  - We studied the putative relaxant effects of several isoprostanes (8-iso-PGE1, and
      8-iso-PGE2, 8-iso-PGF1alpha, 8-iso-PGF1beta, 8-iso-PGF2alpha, and 8-iso-PGF2beta)
      on pulmonary (PA), mesenteric (MA), coronary (CA) arteries and pulmonary veins
      (PV), from newborn and 2-week-old piglets. Isoprostanes were compared with
      agonists of the EP (PGE1, PGE2, and misoprostol), DP (PGD2), and IP (iloprost)
      receptors. Isoprostane-induced relaxation was only observed when TP receptors
      were occupied (by U46619) or blocked (by SQ 29,548). Under these conditions, 8
      iso-PGE2 induced a relaxation of PA (but not PV or MA) that increased with
      postnatal age. 8-iso-PGE1, 8-iso-PGE2, and 8-iso-PGF2alpha evoked modest
      relaxations in CA. 8-iso-PGE2-induced relaxation of PA was impaired by
      endothelium removal and by the presence of blockers of NO synthase (L-NAME),
      guanylate cyclase (ODQ), or EP receptor (AH6809). PGE1, PGE2, and misoprostol
      (but not PGD2 or iloprost) induced a relaxation of PA that increased with age. In
      conclusion, occupancy or blockade of TP receptors unmasked a relaxant effect of 8
      iso-PGE2 in piglet PA. This relaxation increased with postnatal age, was
      endothelium-dependent and involved EP receptors and NO.

PMID- 20036886
TI  - The role of natural killer cells in cancer therapy.
AB  - Natural killer (NK) cells are innate immune cells that have long been known to be
      involved in the recognition and lysis of tumor cells. Despite significant gains
      in our understanding of the mechanisms that regulate NK cell function, the
      development of successful NK cell-based therapies has not yet been achieved.
      However, recent advances in our ability to modulate NK receptor signals and the
      sensitivity of tumor cells to NK cell-mediated lysis have led to a number of
      clinical trials testing novel methods to enhance NK cytotoxicity against cancer.
      Here, we present an overview of current therapies.

PMID- 20036887
TI  - Epac, not PKA catalytic subunit, is required for 3T3-L1 preadipocyte
      differentiation.
AB  - Cyclic AMP plays a critical role in adipocyte differentiation and maturation.
      However, it is not clear which of the two intracellular cAMP receptors, exchange
      protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange
      factor or protein kinase A/cAMP-dependent protein kinase, is essential for cAMP
      mediated adipocyte differentiation. In this study, we utilized a well-defined
      adipose differentiation model system, the murine preadipocyte line 3T3-L1, to
      address this issue. We showed that knocking down Epac expression in 3T3-L1 cells
      using lentiviral based small hairpin RNAs down-regulated peroxisome proliferator
      activated receptor gamma expression and dramatically inhibited adipogenic
      conversion of 3T3-L1 cells while inhibiting PKA catalytic subunit activity by two
      mechanistically distinct inhibitors, heat stable protein kinase inhibitor and
      H89, had no effect on 3T3-L1 adipocyte differentiation. Moreover, cAMP analog
      selectively activating Epac was not able to stimulate adipogenic conversion. Our
      study demonstrated that while PKA catalytic activity is dispensable, activation
      of Epac is necessary but not sufficient for adipogenic conversion of 3T3-L1
      cells.

PMID- 20036888
TI  - A synergism model for PPARalpha and PXR agonist effects on HDL-cholesterol and
      apoA1.
AB  - Synergism between gemfibrozil and CDD 3540, drugs used to elevate mouse serum HDL
      cholesterol and apoprotein A1, is modeled using nonlinear response surface
      techniques. This approach employs a common simple pharmacological model to
      describe the dose-response function. Its parameters are modeled as functions of
      drug mixture fractions using models borrowed from mixture experiment analysis
      methods. This study advances previous in vitro synergy studies in three key
      areas. First, it was in vivo, with the associated additional variability. Second,
      the sample size was much smaller than in previous studies. Finally, this was the
      first specially designed study with this type of statistical analysis in mind.
      The design consisted of replicated observations along each of five rays at
      combination amounts chosen employing the principles of D-optimality. Also, the
      observed in vivo synergism of the combined use of these drugs, elevated levels of
      HDL-C and apoA1, and the experimental results and statistical models may provide
      important clues regarding the biological mechanisms of action of the two
      compounds.

PMID- 20036889
TI  - Expression of VEGF, VEGF-C and VEGFR-2 in in situ and invasive SCC of cervix.
AB  - Cervical squamous cell carcinoma (SCC) arises from the metaplastic epithelium and
      develops slowly through dysplastic changes (i.e., cervical intraepithelial
      neoplasia--CIN) to carcinoma in situ and invasive cancer. There is little data
      concerning the quantitation of vascular endothelial growth factor (VEGF) and its
      correlation to the clinical or pathologic characteristics of SCC. This study
      assessed the expression of VEGF, VEGF-C and their receptor VEGFR-2 in 35 samples
      of normal cervical tissue, 35--CIN1, 35--CIN2 (25 non-pregnant, 15 pregnant
      women), 35--CIN3 and 30- SCC. VEGF, VEGF-C and VEGFR-2 were analyzed using RT
      PCR, RQ-PCR, immunohistochemical staining and Western blot. VEGF, VEGF-C and
      VEGFR-2 were not detected in normal cervical epithelium. In CIN and SCC, both
      forms of VEGF and its receptor were identified, indicating a correlation between
      the increasing expression and staging of carcinoma. Results show the important
      role of VEGF in cervical progression and that the switch to the lymphangiogenesis
      phenotype occurs prior to the stage of invasion likely at CIN2/3.

PMID- 20036890
TI  - Poloxamine-based nanomaterials for drug delivery.
AB  - Poloxamines (Tetronic) are X-shaped amphiphilic block copolymers formed by four
      arms of poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) blocks bonded to a
      central ethylenediamine moiety. Such a structure confers multi-responsive
      behaviour, namely temperature and pH-sensitiveness. At relatively low
      concentrations but above the critical micellar concentration (CMC), poloxamines
      generate polymeric micelles. Due to the presence of a hydrophobic core, these
      nanocarriers are useful in the solubilization and stabilization of poorly water
      soluble drugs. Moreover, chemical modification of the micellar core is feasible.
      These remarkable and unique features, compared to the well-known linear
      poloxamers, have motivated an increasing interest in the study and application of
      the branched derivatives in different emerging disciplines. The present review
      concisely overviews the most important developments comprising the application of
      poloxamines in drug delivery, mainly as micellar carriers capable of enhancing
      drug solubility and stability, and also as surface modifiers in the technology of
      stealth polymeric nanoparticles. Their potential for the administration of drugs
      by different routes and the improvement of the drug bioavailability and
      therapeutic effect are discussed.

PMID- 20036891
TI  - The influence of constitutive COX-2 in smooth muscle tissue on the contractile
      effect of phenylephrine in the rat abdominal aorta.
AB  - Prostanoids are involved in the phenylephrine-induced contraction of the aorta.
      Here, we examined whether or not constitutive cyclooxygenase-2 (phosholipases C
      and A2) is the source of prostanoids in the smooth muscle of the arterial wall of
      the thoracic and abdominal aorta. Both cyclooxygenase isoforms (COX-1 and COX-2)
      were expressed in the two aortic segments, but their expression was not altered
      by phenylephrine, the protein synthesis inhibitor cycloheximide, or the
      phospholipase A2 inhibitors arachidonyl trifluoromethyl ketone and methyl
      arachidonyl fluorophosponate. Indomethacin and NS398, which are a non-selective
      and selective COX-2 inhibitor, respectively, but not SC-560, which is a COX-1
      selective inhibitor, inhibited the effect of phenylephrine on the abdominal, but
      not the thoracic, aorta. Similarly, U73122, which is a phospholipase C inhibitor,
      and RHC80267, which is a diacylglycerol lipase inhibitor, inhibited the effect of
      phenylephrine. These findings suggest that prostanoids, which are produced by
      constitutively active COX-2, influence the contractile response of the abdominal
      aorta and that the production of arachidonic acid relies on phospholipase C and
      diacylglycerol lipase.

PMID- 20036892
TI  - Proteomic analysis of Alternaria alternata (Fr.) Keissler responds to COS
      fumigation.
AB  - Carbonyl sulfide (COS) is a new fumigant which has been a potential alternative
      to methyl bromide and phosphine in many applications. In this study, we
      investigated the fungitoxicity of COS towards the pathogen of pear black spot
      disease Alternaria alternata (Fr.) Keissler (A. alternata). Moreover, proteomic
      analysis and RT-PCR was performed and our results showed that during the
      fumigation, the regulation of 21 proteins in protein expression and mRNA
      accumulation levels is involved, which respond to growth inhibition caused by
      COS. These results provide new clues for the mechanism of the fungitoxicity of
      COS.

PMID- 20036894
TI  - Does exercise really induce lymphocyte apoptosis?
AB  - While the stress associated with acute exercise has been reported to induce
      significant lymphocyte apoptosis, not all investigations have confirmed this
      finding. Regardless of animal or human subjects, exercise-induced lymphocyte
      apoptosis may be induced via an external receptor-mediated pathway, or internally
      via the mitochondria through an oxidative-mediated pathway. On the other hand,
      investigators reporting no effect of acute exercise on lymphocyte apoptosis
      speculate that cell death may be dissociated from these pathways, and explain
      exercise lymphocytopenia by selective migration of the lymphocytes back into the
      lymphoid pools. Discrepancies may be due to sensitivity issues related to the
      methodology used to assess cell death. Limitations to various methods used to
      evaluate exercise-induced lymphocyte apoptosis are detailed, and considerations
      for a new technique are outlined.

PMID- 20036893
TI  - New advances in clinical biomarkers in testis cancer.
AB  - Diagnostic work-up when a testicular cancer is suspected includes a clinical
      examination, determination of risk factors, imaging and serum tumours markers.
      Tumour markers are useful in the diagnosis and staging of disease, for monitor
      the therapeutic response and to detect tumour recurrence. The alpha- fetoprotein
      (AFP) and beta-human chorionic gonadotropin (beta-hCG) are well established as
      serum markers for GCTs of the testis, lactate dehydrogenase (LDH) and placental
      like alkaline phosphatase (PLAP) may be alternative serological markers with less
      specifity. However, these markers are increased in only about 60 per cent of
      patients with testicular cancer. Therefore, additional tumour markers would
      facilitate clinical diagnosis and treatment in these patients. In this review we
      have evaluated the clinical application of several markers of testis cancers in
      serum, semen and tissue samples. Immunohistochemistry detection of some of these
      being solid new markers in addition to the routinely used but none have been
      shown to be superior to the classical markers in serum and semen samples. Further
      research is need in this context for the detection of new markers.

PMID- 20036895
TI  - Clinical biomarkers in esophageal adenocarcinoma.
AB  - This review describes genetic and molecular changes related to adenocarcinoma of
      the esophagus and gastroesophageal junction (GEJ) with emphasis on prognostic
      value and possibilities for targeted therapy in clinical setting. The progression
      of Barrett's esophagus to adenocarcinoma has been the focus of particular
      scrutiny, and a number of potential tissue and serum-based disease biomarkers
      have emerged. Tissue biomarkers allowing risk stratification of Barrett's are
      reviewed as well as strategies currently being used to discover novel biomarkers
      that will facilitate the early detection of esophageal adenocarcinoma.

PMID- 20036896
TI  - Cardiovascular responses to cold exposure.
AB  - The prevalence of hypertension is increased in winter and in cold regions of the
      world. Cold temperatures make hypertension worse and trigger cardiovascular
      complications (stroke, myocardial infarction, heart failure, etc.). Chronic or
      intermittent exposure to cold causes hypertension and cardiac hypertrophy in
      animals. The purpose of this review is to provide the recent advances in the
      mechanistic investigation of cold-induced hypertension (CIH). Cold temperatures
      increase the activities of the sympathetic nervous system (SNS) and the renin
      angiotensin system (RAS). The SNS initiates CIH via the RAS. Cold exposure
      suppresses the expression of eNOS and formation of NO, increases the production
      of endothelin-1 (ET-1), up-regulates ETA receptors, but down-regulates ETB
      receptors. The roles of these factors and their relations in CIH will be
      reviewed.

PMID- 20036898
TI  - Progressive Systemic Sclerosis- from the molecular background to innovative
      therapies.
AB  - Systemic sclerosis (SSc) is a complex autoimmune disorder. The cornerstones of
      the pathogenesis are vascular damage, fibrogenesis and various cellular and
      humoral autoimmune processes. The aim of the present review is to describe
      pathogenic steps, leading to the hallmark clinical picture of SSc. Indeed,
      numerous therapeutical approaches have been tested/are in use, directed towards
      vascular damage, fibrogenesis, as well as autoimmune processes in order to
      decelerate the progression of the disease. These therapies are also discussed in
      the review. Finally, we described certain novel immune-modulating possibilities,
      namely autologous stem-cell transplantation and extracorporeal photochemotherapy.

PMID- 20036897
TI  - Clinical biomarkers in sepsis.
AB  - Sepsis is one of the leading causes of death in intensive care medicine in
      western countries. A strong body of evidence has been accumulated indicating that
      immediate resuscitation and restoration of tissue perfusion as well as early
      antibiotic treatment could significantly decrease the mortality in these
      patients. The clinical definitions of sepsis are basically nonspecific, often
      resulting in the delay of the diagnosis. Therefore, identification of specific
      clinical biomarkers may accelerate the diagnosis and thus improve sepsis
      treatment. During the last decade, a variety of different molecules have been
      proposed as clinical biomarkers in sepsis, most of which are still in the
      experimental stage. However, some have found their way into clinical practice and
      have evolved as valuable tools for diagnosis, therapy monitoring, and outcome
      prediction. This review will summarize the currently most important biomarkers
      and will discuss their clinical relevance.

PMID- 20036899
TI  - Detailed proteomic analysis on DM: insight into its hypoallergenicity.
AB  - Successful therapy in cow milk (CM) protein allergy rests upon completely
      eliminating CM proteins from the child's diet: it is thus necessary to provide a
      replacement food. Donkey milk (DM) has recently aroused scientific and clinical
      interest, above all among paediatric allergologists. A deeper knowledge of
      proteins in DM is necessary to evaluate the immunological and physiological
      properties of this natural substitute for cow's milk. The paper offers a detailed
      comparative analysis among the protein fractions of DM, CM and human milk,
      following an extensive proteomic study of the casein and whey proteins of DM
      performed by narrow pH range 2-DE. The detailed protein composition and
      structural features reported in this study provide insight into the molecular
      reasons for the hypoallergenicity of DM. Whole DM might constitute a valid
      substitute of CM in feeding children with CM protein allergy and it might also
      constitute the basis for formulas suitable for allergic subjects in the first
      year of life.

PMID- 20036900
TI  - Donkey's milk detailed lipid composition.
AB  - Donkey's milk (DM) has recently aroused scientific interest, above all among
      paediatric allergologists. A deeper knowledge of both proteins and fats in
      donkey's milk is necessary to evaluate the immunological, physiological and
      nutritional properties. By using the most refined techniques for fatty acids
      analysis, the paper offers a detailed comparative analysis of the lipid fractions
      of DM as well as of human and cow milk, also indicating the distribution of fatty
      acid moieties among sn-1/3 and sn-2 positions of the glycerol backbone. In DM the
      position of fatty acids on glycerol backbone, above all of long chain saturated
      fatty acids, is very similar to that of human milk: this fact, in conjunction
      with the relatively high contents of medium-chain triglycerides, makes the lipids
      in DM, through quantitatively reduced, highly bioavailable. The high PUFA n-3
      content of donkey's milk, and especially its low n-6/n-3 ratio, acquires
      particular interest in subjects affected by cow's milk protein allergy. Whole DM
      might also constitute the basis for formulas suitable for subjects in the first
      year of life.

PMID- 20036901
TI  - Molecular analysis of Duchenne/Becker muscular dystrophy
AB  - Duchenne (DMD) and Becker muscular dystrophies (BMD) are X-linked recessive
      neuromuscular disorders caused by mutations in the dystrophin gene. In most
      cohorts, DMD/BMD are due to deletions (60-80 per cent) and duplications (6-10 per
      cent) involving one or more exons. The remaining cases are caused by different
      type of point mutations. We analyzed 179 unrelated male patients, 296 women
      belonging to 137 DMD/BMD families, and 93 independent patients referred for
      hyperCKemia. We identified 121 deletions and 11 duplications involving one or
      more exons and one complex rearrangement in the DMD/BMD patients, and 9 deletions
      in males referred for high levels of serum CK. Carrier status was investigated in
      219 female relatives of deleted or duplicated DMD/BMD males, and by linkage
      analysis in 77 women belonging to families in which the causative mutation was
      not identified. Four carrier women with clinical manifestations of the disease
      had unbalanced X inactivation with a degree of X skewing between 70 per cent and
      93 per cent. Large cohort studies from different geographic areas may be
      important for mutation typology comparisons and their appropriate analytical
      approach.

PMID- 20036902
TI  - Hemostatic gene polymorphisms in young Sardinian with non-fatal acute myocardial
      infarction.
AB  - Although the role of environmental factors in the development of acute myocardial
      infarction (AMI) has been clearly established, the role of genetic factors is
      still undefined. The aim of this study was to investigate the association between
      various gene polymorphisms in the haemostatic system and the risk of myocardial
      infarction in a very genetic restricted area population of Sardinian young adults
      with AMI. The study case-control involved 71 patients who had survived a first MI
      at a mean age of 47,2 years and 150 healthy subjects. No differences in the
      allele or genotype frequencies were seen between the study groups for the
      fibrinogen, prothrombin, factor V, factor VII, vWF, TM, PAI-1, TPO gene, and PLA
      and HPA-2 genes polymorphisms. Indeed differences statistically significant were
      detected for A5709G in the TPO gene (P= 0,041), and I/D dimorphism in the eNOS
      gene (P= 0,016). We therefore conclude that among all the investigated
      polymorphisms only the 5709G and eNOS4a alleles seem to confer protection against
      MI in the young age of Sardinian people.

PMID- 20036903
TI  - A novel testis-specific Na+/H+ exchanger is involved in sperm motility and
      fertility.
AB  - Sodium-hydrogen exchanger as a channel for regulation of intracellular pH might
      be a crucial modulator of sperm capacitation and motility. Three members of this
      family have been identified in spermatozoa. A novel protein testis-specific
      sodium-hydrogen exchanger named mtsNHE was cloned in the present study. The
      mtsNHE localizing on principle piece of sperm flagellum contained 12 predicted
      transmembrane regions without cytoplasmic fragment at carboxyl terminus.
      Hydrophilic region was common in the sodium-hydrogen exchanger family members.
      Polyclonal antibodies to trans-membrane region significantly reduced sperm
      motility, acrosome reaction and ratio of in vitro fertilization. By in-pouring
      the antibodies in sperm solution, intracellular pH and calcium concentration were
      decreased. Muscle injection of female mice with the specific gene vaccine of
      mtsNHE, significantly stepped down fertility rate. Considering its specific
      expression and involvement in the regulation of fertility, the mtsNHE might be a
      potential target molecule for developing a new male contraceptive.

PMID- 20036904
TI  - Emax model and interaction index for assessing drug interaction in combination
      studies.
AB  - Applying the Emax model in a Lowe additivity model context, we analyze data from
      a combination study of trimetrexate (TMQ) and AG2034 (AG) in media of low and
      high concentrations of folic acid (FA). The Emax model provides a sufficient fit
      to the data. TMQ is more potent than AG in both low and high FA media. At low
      TMQ:AG ratios, when a smaller amount of the more potent drug (TMQ) is added to a
      larger amount of the less potent drug (AG), synergy results. When the TMQ:AG
      ratio reaches 0.4 or larger in low FA medium, or when the TMQ:AG ratio reaches 1
      or larger in high FA medium, synergy is weakened and drug interaction becomes
      additive. In general, synergistic effect in a dilution series is stronger at
      higher doses that produce stronger effects (closer to 1-Emax) than at lower dose
      levels that produce weaker effects (closer to 1). The two drugs are more potent
      in the low compared to the high FA medium. Drug synergy, however, is stronger in
      the high FA medium.

PMID- 20036905
TI  - Cancer stem cells as new therapeutic target to prevent tumour progression and
      metastasis.
AB  - Over the past decade, increasing evidence suggested that stem cells play a
      crucial role not only in the generation of complex multicellular organisms, but
      also in the development and progression of malignant diseases. For the most
      abundant tumours, it has been shown that they contain a subset of distinct cancer
      cells that is exclusively responsible for tumour initiation and propagation These
      cells are termed cancer stem cells or tumour-initiating cells and they are also
      highly resistant to chemotherapeutic agents. Because CSC are preferentially
      endowed with the self-renewal capacity, it has further been hypothesized that
      they are also exclusively responsible for metastasis. Indeed, we were able to
      show that pancreatic cancer stem cells contain a subpopulation of migrating
      cancer stem cells characterized by CXCR4 co-expression. Only these cells are
      capable of evading the primary tumour and metastasizing. Laboratories around the
      world are now aiming to further characterize these cells to eventually identify
      novel treatment modalities to fight cancer. Thus, cancer stem cells are promising
      new targets to counteract the growth-promoting and metastatic potential of solid
      tumours.

PMID- 20036907
TI  - Characterization of a novel, trastuzumab resistant human breast cancer cell line.
AB  - HER2-positive breast cancers represent a distinct phenotype and are intrinsically
      more aggressive than HER2-negative tumors. Although HER2-targeted therapies have
      been rationally developed, resistance to these treatments represents a process
      understood poorly. There are few experimental models that allow studying the
      molecular mechanism of resistance. Our aim was to characterize a trastuzumab
      resistant breast cancer cell line (B585) that was established from an invasive
      ductal carcinoma. B585 grows only in immunodeficient mice as a xenograft. CGH and
      FISH were used to define cytogenetic alterations, gene-expression analysis and
      immunohistochemistry were applied to detect RNA and protein expression. By array
      CGH focused amplifications were identified for C-MYC, EGFR, ErbB2, CCND1 and TOP2
      A oncogenes. ErbB2 was co-amplified with TOP2-A. mRNA overexpression was detected
      for the amplified genes. ErbB2 protein was overexpressed and showed heterogeneous
      distribution. In summary, molecular cytogenetic analysis and expression profiling
      of B585 revealed several new alterations. Based on the experiments performed in
      SCID mice and the genotypic/phenotypic characteristics, this new in vivo breast
      cancer xenograft is a valuable model to investigate molecular mechanism of
      trastuzumab resistance.

PMID- 20036908
TI  - Molecular markers for prostatic cancer.
AB  - Prostate cancer (caP) is a major public health problem. Many groups have
      attempted to identify prognostic risk factors to early detect caP and to identify
      who will need active treatment. Since the introduction of prostate specific
      antigen (PSA), diagnosis of caP has increased even as mortality for prostatic
      cancer has declined. Using current recommended guidelines, the PSA test suffers
      from both of limited specificity and sensitivity. With the aim to improve early
      detection of prostatic cancer the volume adjusted PSA, PSA isoforms and PSA
      kinetics have been investigated. Recently, technological advances in molecular
      assays have led to the discovery of new markers with high specificity. Further,
      proteomic array profiling and DNA methylation assays could provide for more
      accurate diagnosis and prognosis. Current evidence suggests that no single marker
      is likely to achieve the desired level of diagnostic and prognostic accuracy:
      future research should focus on validation of already existing biomarkers and the
      discovery of new markers to identify men with aggressive prostate cancer and to
      predict outcomes after therapies.

PMID- 20036906
TI  - Nitroxyl enhances myocyte Ca2+ transients by exclusively targeting SR Ca2+
      cycling.
AB  - Nitroxyl (HNO), the 1-electron reduction product of nitric oxide, improves
      myocardial contraction in normal and failing hearts. Here we test whether the HNO
      donor Angeli's salt (AS) will change myocyte action potential (AP) waveform by
      altering the L-type Ca2+ current (ICa) and contrast the contractile effects of
      HNO with that of the hydroxyl radical (.OH) and nitrite (NO2-), two potential
      breakdown products of AS. We confirmed the positive effect of AS/HNO on basal
      cardiomyocyte function, as opposed to the detrimental effect of .OH and the
      negligible effect of NO2-. Upon examination of the myocyte AP, we observed no
      change in resting membrane potential or AP duration to 20 per cent repolarization
      with AS/HNO, whereas AP duration to 90 per cent repolarization was slightly
      prolonged. However, perfusion with AS/HNO did not elicit a change in basal ICa,
      but did hasten ICa inactivation. Upon further examination of the SR, the AS/HNO
      induced increase in cardiomyocyte Ca2+ transients was abolished with inhibition
      of SR Ca2+-cycling. Therefore, the HNO-induced increase in Ca2+ transients
      results exclusively from changes in SR Ca2+-cycling, and not from ICa.

PMID- 20036909
TI  - A comparative study on two phenylboronic acid based glucose-sensitive hydrogels.
AB  - Two phenylboronic acid based glucose-sensitive hydrogels, A.PBA-DMAPMA-EGDMA and
      A.PBA-PEG, were initially prepared by free-radical polymerization. Swelling
      properties of the gels were studied by determining the diameter changes in
      different buffer solutions, with or without glucose or fructose. The hydrogels
      were designed as "valves" to control the flow of glucose solutions. The results
      showed that gel A.PBA-DMAPMA-EGDMA was sensitive to pH and glucose, but not to
      fructose. It shrunk in weak basic solution and the addition of glucose made it
      shrink more. In this gel PBA moiety and glucose is supposed to form a 1:2 bis
      bidentate complex. Hydrogel A.PBA-PEG was sensitive to pH, glucose and fructose,
      all of which made it swell in weak basic solution. A 1:1 complex is believed to
      form between PBA and glucose/fructose in this gel. All the stimuli-responses are
      reversible and the glucose-responses occurred in the range of the
      physiological/pathological glucose level. Both A.PBA-DMAPMA-EGDMA and A.PBA-PEG
      exhibited sufficient volume change to the alteration of glucose concentration and
      could be employed as a "valve" to control liquid flow in weak basic solution.

PMID- 20036911
TI  - Steroidogenesis in the brain of Sepia officinalis and Octopus vulgaris.
AB  - The presence of vertebrate-like steroids, steroidogenic enzymes and steroid
      receptors has been reported exclusively in cephalopods gonads. The role played by
      these steroids has been also recently investigated. We here give evidence of
      steroidogenic activity in the brain of cephalopods. The activity of two key
      steroidogenic enzymes: 3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD is
      present in the lobes of the nervous system of both Sepia and Octopus. Such
      enzymes convert pregnenolone to progesterone and androstenedione to testosterone
      respectively. Binding experiments seem to assign a functional role to the
      androgens in the brain of cephalopods. According to the present results, the
      absence of any progesterone binding moiety supports the hypothesis that
      progesterone may be a metabolite product along the steroidogenic chain leading to
      androgens. The presence of steroidogenic enzymes in specific lobes of the central
      nervous system is discussed in terms of the possible role that steroids can play
      in the sexual differentiation of the brain and in influencing some coded
      behaviours of cephalopods, such as learning processes.

PMID- 20036910
TI  - In vitro drug interactions of gallates with antibiotics in Staphylococcus Aureus.
AB  - The antimicrobial activities of tetracycline, mupirocin, and fusidic acid are
      tested in combination with Epicatechin Gallate (ECG), and Ethyl Gallate (EG)
      using 2 Methicillin resistant (MRSA) and 2 Methicillin sensitive (MSSA) strains
      of Staphylococcus aureus. Sub-inhibitory concentration of EG at 256 mg l-1 is
      found to be synergistic when used in combination with tetracycline, mupirocin,
      and fusidic acid; and a sub-inhibitory concentration of ECG at 32 mg l-1 is found
      to be synergistic with tetracycline in all the four Staphylococcus aureus strains
      tested. The synergistic combinations reduce the MICs of all the above three
      antibiotics by 4 fold. Combining ECG at 32 mg l-1 with mupirocin, reduces the MIC
      of mupirocin by four fold in MSSA C1 strain. 74 per cent of the combinations show
      consistent results in both time-kill assay and checkerboard method. The
      identified combinations may lead towards novel therapeutic interventions for
      treating MRSA infections.

PMID- 20036912
TI  - Beta-cyclodextrin in DNA decompaction: an imaging approach.
AB  - In the present work we investigate the CTAB:DNA complexes decompaction process
      using beta-CD as a decompacting agent. The transition from globules (compacted
      DNA) to coils (decompacted DNA) was achieved without a coexistence region between
      coils and globules. This non first-order transition was investigated combining
      fluorescence microscopy (FM), cryo-transmission electron microscopy (cryo-TEM)
      and TEM of negatively stained samples. Additionally the presence of multi
      globular aggregates in the proximity of the critical transition was elucidated. A
      possible mechanism for the decompaction process was suggested.

PMID- 20036913
TI  - Colorectal cancer detection by means of optical fluoroscopy. A study on 494
      subjects.
AB  - In the present work we investigated the possible role of the native fluorescence
      of blood plasma in the management of colorectal cancer (CRC) and its feasibility
      as a new tumor marker. Sample of blood was collected from 248 asymptomatic blood
      donors and from 246 CRC patients. The native fluorescence of blood plasma was
      measured using a conventional spectrofluorimeter. The intensity of fluorescence
      of blood plasma at 623 nm (IF623), reasonably ascribed to endogenous porphyrins,
      was significantly higher in CRC patients than in healthy subjects. The diagnostic
      capability of IF623 in the discrimination between healthy subjects and CRC
      patients was tested by Receiving Operating Characteristic (ROC) curve analysis,
      which resulted in an Area Under the Curve (AUC) of 0.72+/-0.01. Fluorescence
      measurement of blood plasma might be considered diagnostically useful as a
      candidate for a new tumor marker for CRC management. The procedure is
      characterised by a great acceptability and by a very low cost, and might be used
      in a two-step screening wherein an IF623 positive result is followed by
      colonoscopy.

PMID- 20036914
TI  - The aristaless (Arx) gene: one gene for many "interneuronopathies".
AB  - The ARX (Aristaless-related (X-linked) homeobox) gene is not only present in
      arthropods and their ancestors, but also in vertebrates including humans (ARX
      orthologs). The gene is composed of 5 coding exons and it is expressed
      predominantly in foetal and adult brain and skeletal muscle. In this review we
      report on our experience and review the existing literature on the genotype and
      phenotype heterogeneity associated with ARX abnormalities in humans ranging from
      severe neuronal migration defects (e.g., lissencephaly), to mild forms of X
      linked mental retardation without apparent brain abnormalities. The ARX-related
      disorders are reviewed focusing on their clinical features and on the role of the
      ARX gene. It has yet to be established whether the molecular defect alone could
      cause a given cerebral abnormality and/or malformation or an additional or
      related molecular or environmental event could contribute to a given phenotype in
      molecularly.

PMID- 20036915
TI  - Liver cell-mediated alleviation of acute ischemic myocardial injury.
AB  - Cardiomyocyte injury occurs in myocardial ischemia, resulting in impairment of
      cardiac function. As the endogenous protective function of adult cardiomyocytes
      is limited, nonmyocytic cells may be activated to protect myocardium from
      ischemic injury. In this investigation, we demonstrated in a mouse model of
      myocardial ischemia that the liver was able to respond to myocardial ischemia to
      upregulate a number of genes encoding secreted proteins, mobilize its cells, and
      release cell contents into the circulatory system. These naturally occurring
      mechanisms suggested a possible cardioprotective role for myocardial ischemia
      conditioned liver cells and inspired us to develop cardioprotective therapies
      based on these mechanisms. We demonstrated that administration of liver cell
      extract derived from myocardial ischemic mice, but not sham control mice,
      resulted in a significant reduction in acute myocardial infarction as well as the
      density of TUNEL+ cells in ischemic myocardium compared to administration of PBS
      at 2, 6, 12, and 24 hrs. These observations suggest that liver cells may respond
      to myocardial ischemia to express cardioprotective factors, which may be
      identified and used for alleviating myocardial infarction.

PMID- 20036916
TI  - 1H NMR-based metabolic profiling of urine from children with nephrouropathies.
AB  - Pediatric nephrourological diseases are associated with functional alterations
      frequently related to inflammatory states. A feedback loop adjusts urinary system
      function while forcing adaptation to internal and external influences during
      disease development and as a result of treatment. We hypothesized that
      nephrourological dysfunction would alter the urine metabolite pattern in children
      in a defined manner. To characterize the metabolite patterns associated with
      nephrouropathies, a proton nuclear magnetic resonance (1H NMR)-based metabonomic
      analysis was performed on urine samples obtained from twenty-one children
      affected by nephrouropathies and 19 healthy controls. Urine samples were analyzed
      with a 400 MHz Varian spectrometer and multivariate statistical techniques were
      applied for data interpretation. Linear discriminant analysis-based
      classification of the spectral data demonstrated high accuracy (95 per cent) in
      the separation of the two groups of samples. The urine metabolite profiles were
      shown to correlate with nephrourological disorders in our model. In conclusion,
      1H NMR-based metabonomic analysis of urine appears to be a promising, non
      invasive approach to investigate and monitor pediatric nephrourological diseases.

PMID- 20036917
TI  - Italy-Japan agreement and discrepancies in diagnosis of superficial gastric
      lesions.
AB  - The agreement between Italian and Japanese endoscopists and pathologists on
      endoscopic and histopathological diagnoses of superficial gastric lesions is
      verified with the use of Paris and Vienna classifications. The correlations
      between Paris endoscopic types and Vienna histopathological categories is high in
      both the independent Italian and Japanese evaluations. However, the agreement
      between Italian and Japanese endoscopists is moderate due to the difficult
      evaluation of the height of the lesions, in particular when they are mixed. The
      agreement on the size of the lesions is fairly good. The probability of the same
      allocation to the Vienna categories of a single case is 87 per cent,
      disagreements remaining in dysplasia grading, between dysplasia, not only high
      grade but also low-grade, and in situ carcinoma, and on cancer invasion of the
      lamina propria. The results indicate that use of the Paris and Vienna
      classifications has reduced the discrepancies between Western and Japanese
      endoscopists and pathologists in the diagnosis of these lesions.

PMID- 20036918
TI  - Immunolocalization of mitoKATP subunits in human osteoblast-like cells.
AB  - The mitochondrial ATP-dependent K channel (mitoKATP) has been shown to play a
      role in cellular protection against apoptosis, or programmed cell death. This
      channel has been identified and characterized in a number of cell and tissue
      types but to date the possible existence of mitoKATP in osteoblastic cells has
      not been investigated. The aim of this investigation was to establish whether the
      mitochondria of human osteosarcoma-derived osteoblasts (SaOS-2 cells) contain the
      putative mitoKATP subunits Kir6.1 and Kir6.2. Ultrathin sections of SaOS-2 cells
      were prepared for transmission electron microscopy using an adaptation of the
      Tokuyasu method, and immunolabelled using goat anti-Kir6.1 or anti-Kir6.2
      antisera as the primary label, and a 10nm colloidal gold-conjugated donkey anti
      goat secondary antibody. The suitability of the antisera and the immunostaining
      protocol were confirmed by using a sample of rat cardiac muscle as a positive
      control. Ultrastructural analysis revealed that SaOS-2 cells contain Kir6.2 but
      not Kir6.1, and that Kir6.2 is present in the mitochondria, but in extremely low
      abundance. These findings suggest that human osteoblast-like cells might contain
      mitoKATP channels in which Kir6.2 is the pore-forming subunit, although it
      appears that these channels are likely to be present in extremely low abundance.

PMID- 20036919
TI  - AtTFC B is involved in control of cell division.
AB  - Tubulin-folding cofactors play important roles in regulating plant development.
      Arabidopsis tubulin-folding cofactor B (AtTFC B) is an Arabidopsis homolog of
      mammalian tubulin-folding cofactor B, whose biological function in plant
      development remains poorly understood. Here we report that the homozygous attfc b
      (-/-) allele caused embryonic lethality. Embryogenesis was arrested at early
      embryo stage and the cells contained one or multiple nuclei. Plants carrying a
      heterozygous attfc b (+/-) allele exhibited enlarged mesophyll cells and leaf
      epidermal cells with bulged nuclei. Flow cytometry analysis showed increased
      ploidy in the leaves of the attfc b (+/-) mutant, as well as increased levels of
      Cdc2A and CycB1;1. In addition, immunofluorescence assay showed increased numbers
      of spindles and phragmoplasts in the attfc b (+/-) mutant. These results suggest
      that AtTFC B plays an important role in plant cell division.

PMID- 20036920
TI  - Effect of genistin on bone formation.
AB  - The amount of new bone produced by grafting genistin in collagen matrix was
      compared to the bone produced by collagen matrix alone. A total of 18 bone
      defects (5 mm by 10 mm) were created in the parietal bone of 9 New Zealand White
      rabbits. Six defects were grafted with genistin mixed with collagen matrix, while
      6 were grafted with collagen matrix alone (positive control) and 6 were left
      empty (negative control). Animals were killed on day 14 and defects were prepared
      histologically. Quantitative analysis of new bone formation and bone cells was
      carried out on 100 sections (50 sections for each group) using image analysis. A
      total of 520 per cent more new bone was present in defects grafted with genistin
      in collagen matrix than in defects grafted with collagen matrix alone (p less
      than 0.0001), while no bone was formed in the negative control group. The amount
      of bone forming osteoblasts was also significantly greater in the genistin group
      than the positive control group. Therefore, genistin in collagen matrix can
      increase new bone formation locally in vivo.

PMID- 20036921
TI  - Clinical biomarkers and management of post thrombotic syndrome.
AB  - The post-thrombotic syndrome (PTS) is a long-term complication of deep venous
      thrombosis (DVT) that is characterized by chronic, persistent pain, swelling and
      other signs in the affected limb. PTS is common, burdensome and costly. It is
      likely to increase in prevalence, since despite widespread use of and
      improvements in the efficacy of thromboprophylaxis, the incidence of DVT has not
      decreased over time. Preventing ipsilateral recurrence of DVT, by ensuring an
      adequate duration and intensity of anticoagulation for the initial DVT and by
      prescribing situational thromboprophylaxis after discontinuation of oral
      anticoagulants, is likely to reduce the risk of developing PTS. Pending the
      results of ongoing studies, stockings are recommended in patients with persistent
      symptoms or swelling after DVT. Future research should focus on standardizing
      criteria for PTS diagnosis, identification of DVT patients at high risk for PTS,
      and rigorously evaluating the effectiveness of stockings, thrombolysis, and
      venoactive drugs in preventing or treating PTS.

PMID- 20036922
TI  - CNS fatigue provoked by prolonged exercise in the heat.
AB  - Exercise-induced hyperthermia is associated with central fatigue as indicated by
      an impaired ability to sustain maximal motor activation during prolonged
      voluntary efforts. Therefore, exercise in hot environments challenges not only to
      the cardiorespiratory and locomotive systems but also to the brain. However,
      exercise with superimposed hyperthermia is not only a challenge to the brain it
      also provides an excellent model for studying factors of importance for central
      fatigue. Excessive heat storage within the brain appears to be the primary cause
      for the central fatigue during exercise in the heat, but pharmacological
      manipulations provide evidence for involvement of the dopaminergic system and
      other monoamines. Thus, enhanced dopaminergic activity may counteract
      hyperthermia mediated central fatigue and improve performance in the heat, while
      noradrenaline re-uptake inhibition appears to aggravate central fatigue and
      degrade exercise performance. Hyperthermia mediated central fatigue may include
      other cerebral perturbations such as reduced perfusion of the brain, accumulation
      of ammonia or depletion of neuronal energy stores, but further research is needed
      to elucidate their possible contributions.

PMID- 20036923
TI  - SNPs: At the origins of the databases of an innovative biotechnology tool.
AB  - The discovery that DNA sequence variations can influence the response of an
      individual to a drug or can predict the outcome of a disease has added a new
      dimension to evidence-based medicine. It is clear that the goals, risks, and
      benefits of drug therapy can be better assessed if the underlying genome of the
      patient is known. The relevance of identifying patients at increased risk of
      adverse drug reactions, the application of genomic technologies to drug
      development and the clarification of the mechanisms of drug action on cells will
      be important targets in the therapeutic approach to medicine in the 21st century.
      In this review, we summarize the development of single nucleotide polymorphisms
      (SNPs) and give computational biological data for SNPs databases.

PMID- 20036924
TI  - Animal ethics in SIRS research.
AB  - It is well recognized that animals play a vital role and are indispensable to
      scientific and medical research. Over the years, a number of non-animal
      procedures have been developed. However, despite all the advances in science, as
      yet, no system has been evolved which can completely replace a living system to
      conduct basic research. There is still a need to test food, drugs, medical
      devices, treatment regimes etc. on some animals before they can be tested and
      used (if found suitable) in human beings. Even the most sophisticated technology
      models have failed to mimic completely the complex cellular interactions
      occurring in a living system. The search for a complete alternative to animal
      research is still on and in the mean time we can all help play our part by
      conducting animal research in a humane and responsible fashion. This chapter
      discusses the ethical issues in animal research highlighting the need to use
      animals conscientiously.

PMID- 20036925
TI  - The shady side of sunlight: current understanding of the mechanisms underlying UV
      induction of skin cancers.
AB  - The incidence of skin cancer has been rising at an astonishing rate, particularly
      that of the deadliest skin cancer, melanoma. While the molecular mechanisms of
      sunlight ultraviolet radiation (UV)-induced non-melanoma skin cancer (NMSC) have
      been well documented, there is a major gap in our current knowledge of how UV
      initiates melanoma. However, the components of the retinoblastoma (Rb) pathway,
      the p53 and the p16 pathways are considered the major targets of UV-induced NMSC
      and melanoma, respectively. Our recent study has revealed that these two pathways
      coordinate the early responses to UV radiation in the skin. Here, we review the
      value of studies targeting these early events of skin carcinogenesis, with
      specific focus on the critical role of the components of the Rb pathway.

PMID- 20036926
TI  - The role of nitric oxide and reactive nitrogen species in experimental ARDS.
AB  - The acute respiratory distress syndrome (ARDS) is associated with a mortality
      ranging between 40 - 80%. An effective drug therapy, however, is still missing.
      Many experimental models of ARDS exist enabling a better understanding of the
      underlying pathophysiology and allowing the establishment of novel therapeutic
      strategies for the treatment of patients suffering ARDS. Nitric oxide (NO) and
      reactive nitrogen species (RNS) are increasingly regarded as key substances
      within the development of ARDS. However, the definite pathomechanism is not
      completely understood. The purpose of this article is to review the latest
      results of experimental studies in reference to the role of NO and RNS in the
      pathogenesis of ARDS. In addition, current large animal models of ARDS are
      described and future therapeutic approaches are discussed.

PMID- 20036927
TI  - Disturbed sleep: linking allergic rhinitis, mood and suicidal behavior.
AB  - Allergic inflammation is associated with mood disorders, exacerbation of
      depression, and suicidal behavior. Mediators of inflammation modulate sleep ,
      with Th1 cytokines promoting NREM sleep and increasing sleepiness and Th2
      cytokines (produced during allergic inflammation) impairing sleep. As sleep
      impairment is a rapidly modifiable suicide risk factor strongly associated with
      mood disorders, we review the literature leading to the hypothesis that allergic
      rhinitis leads to mood and anxiety disorders and an increased risk of suicide via
      sleep impairment. Specifically, allergic rhinitis can impair sleep through
      mechanical (obstructive) and molecular (cytokine production) processes. The high
      prevalence of mood and anxiety disorders and allergy, the nonabating suicide
      incidence, the currently available treatment modalities to treat sleep impairment
      and the need for novel therapeutic targets for mood and anxiety disorders,
      justify multilevel efforts to explore disturbance of sleep as a
      pathophysiological link.

PMID- 20036929
TI  - Development of microfluidic-based heterogeneous immunoassays.
AB  - Microfluidic-based heterogeneous immunoassays are reviewed in this article by
      first introducing the principle of immunoassay, followed by a discussion of
      microfluidic-based technology. Microfabrication, surface modification, solution
      dispensing and detection technology are discussed and their applications to
      biomolecular detection reviewed. In the future, improved manufacturing processes
      and integrated assay systems in an automatic fashion with a reduced assay time
      and reagent consumption will allow for the effective detection of biomolecules
      that are of interest in medical diagnostics, drug discovery and bioterrorism.

PMID- 20036928
TI  - Biochemical markers of perinatal brain damage.
AB  - Hypoxia-ischemia constitutes a risk in infants by altering cerebral blood flow
      regulatory mechanisms and causing loss of cerebral vascular auto-regulation.
      Hypotension, cerebral ischemia, and reperfusion are the main events involved in
      vascular auto-regulation leading to cell death and tissue damage. These dramatic
      phenomena represent a common repertoire in infants complicated by perinatal acute
      or chronic hypoxia. To date, despite accurate perinatal and intra-operative
      monitoring, the post-insult period is crucial, since clinical symptoms and
      monitoring parameters may be of no avail and therapeutic window for
      pharmacological intervention (6-12 hours) may be limited, at a time when brain
      damage is already occurring. Therefore, the measurement of circulating
      biochemical markers of brain damage, such as vasoactive agents and nervous tissue
      peptides is eagerly awaited in clinical practice to detect high risk infants. The
      present review is aimed at investigating the role as circulating biochemical
      markers such as adrenomedullin, S100B, activin A, neuronal specific enolase
      (NSE), glial fibrillary acid protein (GFAP), in the cascade of events leading to
      ischemia reperfusion injury in infants complicated by perinatal asphyxia.

PMID- 20036930
TI  - Lissencephalic syndromes: brain and beyond.
AB  - Lissencephaly has been long maintained a malformation involving only the brain.
      Classic lissencephaly includes agyria and pachygyria and it is the most severe
      form of malformations derived from abnormal neuronal migration. It is defined as
      a smooth or nearly smooth cerebral surface with absence of normal sulci and
      gyria. It encompasses a group of syndromes which show many different clinical
      conditions. Four groups are actually distinguished: classic lissencephaly
      variants, other lissencephalies including forms with unknown pathogenesis,
      microlissencephaly spectrum and Cobblestone cortical malformations. Several genes
      and proteins are involved in this syndromic spectrum and each year new molecular
      data are reported in the literature: classifications in this sense are always in
      progress. Lissencephaly now is recognised to involve not only the brain but also
      several other organs and districts including eyes, face, muscles, genital organs,
      heart and bones. Mental retardation and different form of epilepsies usually drug
      resistant are the main clinical signs. The Authors in this topic discuss on this
      subject, underlying the different forms of lissencephaly their wide heterogeneity
      and the complex involvement of several organs.

PMID- 20036931
TI  - Persistent low-grade inflammation and regular exercise.
AB  - Persistent low-grade systemic inflammation is a feature of chronic diseases such
      as cardiovascular disease (CVD), type 2 diabetes and dementia and evidence exists
      that inflammation is a causal factor in the development of insulin resistance and
      atherosclerosis. Regular exercise offers protection against all of these diseases
      and recent evidence suggests that the protective effect of exercise may to some
      extent be ascribed to an anti-inflammatory effect of regular exercise. Visceral
      adiposity contributes to systemic inflammation and is independently associated
      with the occurrence of CVD, type 2 diabetes and dementia. We suggest that the
      anti-inflammatory effects of exercise may be mediated via a long-term effect of
      exercise leading to a reduction in visceral fat mass and/or by induction of anti
      inflammatory cytokines with each bout of exercise.

PMID- 20036932
TI  - The placebo response in pain and depression: in search of a common pathway.
AB  - The placebo effect has been extensively studied in many disease states, some of
      the most notable being pain and depression. Utilizing a Medline search, studies
      were identified that reported on areas of the brain shown to be involved in
      either placebo analgesia or mood response. This paper presents a distillation of
      this research, in an effort to identify a common "placebo pathway" between mood
      and pain. Placebo-related responses to both analgesia and relief from depression
      were reported to be associated with an increase in activity in the frontal cortex
      and a decrease in activity in the thalamus.

PMID- 20036933
TI  - Dilated cardiomyopathy: etio-morphologic investigation.
AB  - The heart is the first organ to form and to function during vertebrate
      embryogenesis and its correct functionality is a "conditio sine qua non" for
      life. If the heart's pumping power is compromised, chambers dilate and pulmonary
      and systemic circulations are altered. Dilated cardiomyopathy can appear along a
      wide spectrum of presentations, including no symptoms, subtle symptoms or heart
      failure, which occurs when the heart is unable to pump blood to the periphery and
      oxygenate the organs. Dilated cardiomyopathy, the most common form of
      cardiomyopathy, is characterized by a particular complex of nonspecific
      pathologic features that do not necessarily identify the different etiologies. In
      this study, we review the etiologic and morphologic features of 86 explanted
      recipient adult hearts with dilated cardiomyopathy undergoing orthotopic heart
      transplantation between 1997 and 2008.

PMID- 20036934
TI  - Molecular and functional genetics of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer and one of the
      leading causes of cancer death worldwide. Hepatocarcinogenesis is a multistep
      process developing from normal through chronic hepatitis/cirrhosis and dysplastic
      nodules to HCC. Although we have insufficient understanding to propose a robust
      general model, with advances in molecular methods, there is a growing
      understanding of the molecular mechanisms in the development of HCC.
      Hepatocarcinogenesis is strongly linked to increases in allelic losses,
      chromosomal changes, gene mutations, epigenetic alterations, and alterations in
      molecular cellular pathways. Special emphasis in this review is given to the
      genetics, epigenetics, and regulation of major signaling pathways involved in HCC
      such as Wnt/b-catenin, Ras, and PI3K/Akt/mTOR pathways. A detailed understanding
      of the underlying molecular mechanisms involved in the progression of HCC can
      improve our prevention and diagnostic tools for HCC and be an important potential
      source of novel molecular targets for new therapies.

PMID- 20036935
TI  - Airborne inflammatory factors: "from the nose to the brain".
AB  - The intranasal pathway is a direct route of communication between the environment
      and the brain. This pathway is currently used for the delivery of several
      experimental therapeutic peptides and vaccines because it bypasses the blood
      brain barrier. It is also a route of entrance to the brain for several viruses
      and toxic substances. Airborne infectious, allergic and pollution agents are
      among the most common inflammatory factors which may affect brain function via
      the brain-nose interface. The inflammatory processes triggered in the upper
      respiratory tract by these agents are positioned to influence the immune response
      of the brain and therefore, influence its function and alter behavior. Several
      clinical and epidemiological studies find an association between inflammatory
      factors affecting the intranasal pathway and neurological disorders such as
      multiple sclerosis, Alzheimer and Parkinson diseases as well as mental disorders
      including anxiety and mood disorders. However the mechanisms of interaction
      between the immune response in the nasal epithelium and the brain are poorly
      understood. This article discusses current evidence about these mechanisms and
      associations with neurological and mental diseases.

PMID- 20036937
TI  - Emerging role of resveratrol in the treatment of severe acute pancreatitis.
AB  - Severe acute pancreatitis (SAP) develops in 15-20% of patients with acute
      pancreatitis. The management of SAP is a challenging task owing to the fact that
      it can lead to morbid conditions like multiple organ failure and systemic
      inflammatory response syndrome, if left untreated. Resveratrol, a drug used in
      Chinese traditional medicine has shown potential to treat many symptoms of SAP
      due to its multiple physiological actions. It possesses anti-inflammatory and
      anti-oxidative properties, both of which are essential in SAP. NF-kappaB
      activation is a major source of pro-inflammatory mediators in SAP. Administration
      of resveratrol can inhibit NF-kappaB activity as well as reduce the
      concentrations of TNF-alpha, IL-6 and IL-1. It can also scavenge reactive oxygen
      species that are capable of extensive tissue damage. Furthermore, resveratrol
      also exhibits anti-apoptotic properties via regulation of apoptotic mediators
      such as Bax, Bcl-2, and caspase-3. It also plays a role in calcium regulation and
      alleviates SAP-induced histopathological distortions in the pancreas. These multi
      faceted results support the use of resveratrol in SAP and mandate the need for
      extensive research on this molecule.

PMID- 20036938
TI  - Roles of inflammation in cancer initiation, progression, and metastasis.
AB  - Inflammatory cells and signals contribute to the initiation and development of
      cancer. In fact, persistent inflammatory conditions resulting from infection or
      injury can exist before a normal cell is transformed into a cancer cell.
      Situations of chronic inflammation can promote genomic instability leading to DNA
      damage, oncogene activation, or impaired function of a tumor suppressor.
      Alternatively, cancer development unrelated to inflammation can stimulate the
      development of an inflammatory microenvironment that promotes tumor cell
      proliferation. Whether chronic or tumor-derived, inflammation and inflammation
      related stimuli within the tumor microenvironment permits proliferation and
      survival of cancer cells, promotes blood and lymphatic vessel formation, and aids
      in invasion and metastasis. The inflammatory status of the tumor microenvironment
      can act to quell the body's natural immune response and effectively ameliorate a
      positive response to many commonly used anti-cancer antibodies and
      chemotherapeutic agents. New evidence suggests that the molecular pathways and
      consequences of inflammation specifically related to the tumor microenvironment
      are starting to be understood. This new information implicates novel cellular
      targets that could lead to improved diagnosis and treatment for a variety of
      solid malignancies.

PMID- 20036936
TI  - Chemokines and chemokine receptors in arthritis.
AB  - Chemokines are involved in leukocyte recruitment to inflammatory sites, such as
      the synovial tissue in rheumatoid arthritis (RA). There is a structural and a
      functional classification of chemokines. The former includes four groups: CXC,
      CC, C and CX3C chemokines. Chemokines may also be either inflammatory or
      homeostatic, however, these functions often overlap. Anti-chemokine and anti
      chemokine receptor targeting may be therapeutically used in the future biological
      therapy of arthritis. Most data in this field have been obtained from animal
      models of arthritis as only very few human RA trials have been completed.
      However, it is very likely that various specific chemokine and chemokine receptor
      antagonists will be developed and administered to RA patients.

PMID- 20036939
TI  - Cancer stem cell and niche.
AB  - Recent research on cancer has generated a new model for cancer growth-cancer stem
      cell model. This model can explain the inefficiency of conventional therapy.
      Tumor tissue, like normal tissue, is continuously repopulated from pools of self
      renewing stem cells growing in a "niche", which is made up of a specialized
      vascular bed of endothelial cells, associated cells of mesenchymal origin and
      extracellular matrix components. In this review, we will introduce the models of
      cancer development, the roles of stem cells in tumor progression, the components
      of niche which affects the cell fate of cancer stem cells (CSCs), their different
      regulatory factors, as well as the clinical implication of CSCs in cancer
      treatment.

PMID- 20036940
TI  - Pathophysiology of the proatherothrombotic state in the metabolic syndrome.
AB  - Obesity and insulin resistance are very frequently associated to the metabolic
      syndrome (MetS), play a pivotal role in the development of type 2 diabetes
      mellitus (T2DM) and increases the risk of cardiovascular disease. Although it
      varies among ethnic groups, the worldwide prevalence of MetS is 23% in young
      adults and increases with age. Remarkably, the prevalence of MetS is expected to
      rise during the next decades due to the acquisition of unhealthy life-style
      habits (sedentarism, smoking, unhealthy diet). A major pathological alteration
      present in the MetS is a prothrombotic state resulting from endothelial
      dysfunction and hypercoagulability produced by a dysbalance of coagulation
      factors and proteins regulating fibrinolysis. Although intensive research in
      recent years has identified a number of prothrombotic alterations in MetS
      patients, a better understanding of the molecular mechanisms underlying the
      relationship between MetS and atherotrombosis is required to improve prevention
      and treatment. In this review we discuss the main alterations in the endothelial
      function, coagulation cascade, fibrinolysis and platelet function promoting
      atherothrombosis in MetS and available mouse models exhibiting alterations in
      atherothrombosis.

PMID- 20036941
TI  - Enzymes and bioscavengers for prophylaxis and treatment of organophosphate
      poisoning.
AB  - Organophosphorus (OP) pesticide poisoning causes significant morbidity and
      mortality, particularly in the developing world, with upwards of 3 million people
      poisoned each year. Although OP poisoning is not common in developed countries,
      recently greater attention has been given to these chemicals because of their
      similarity to chemical warfare agents. Despite the agricultural use of OP
      pesticides for roughly 60 years, no new therapies have been developed since the
      1960s. A promising field of novel antidotes for OP poisoning, OP hydrolases, has
      recently garnered increased support. These bacterial enzymes have demonstrated
      tremendous prophylactic and antidotal efficacy against a few different OP classes
      in animal models. These studies, as well as the limitations and challenges of
      therapeutic development of these enzymes, are discussed.

PMID- 20036942
TI  - Novel therapeutic approaches in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a prototypical systemic autoimmune disease,
      affecting multiple organs and organ-systems, leading to a wide variety of
      symptoms, serological and clinical features. The pathogenesis of the disease
      encompasses a complex interplay among various immune-competent cells and
      inflammatory mediators, which gives ground to target numerous potentially harmful
      players in this system. The aim of the present review was to depict certain
      aspects on the pathogenesis of SLE and to highlight pathways that can be
      promising targets of novel therapeutic approaches. T-cell, B-cell targeting,
      modification of co-stimulatory pathways, anti-cytokine therapy, soluble
      mediators, as well as autologous stem cell transplantation have been addressed.
      Finally, we described potential side effects of these biologics.

PMID- 20036943
TI  - EMT and TGF-beta in renal fibrosis.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a member of TGF-beta superfamily
      and the principal mediator contributing to the development and progression of
      renal fibrosis in a variety of disease settings. A critical effect of TGF-beta1
      is the induction of epithelial-mesenchymal transition (EMT), which likely
      explains the continuous replenishment of fibroblasts during the progression of
      tissue fibrosis. Since we first identified EMT as the origin of fibroblasts in
      renal fibrosis, the signaling underlying EMT has been intensively studied in the
      field of nephrology. During the past five years, detailed mechanisms by which TGF
      beta1 induces EMT have been clarified, and novel therapeutic approaches targeting
      TGF-beta1-mediated EMT are now being proposed.

PMID- 20036944
TI  - Effects of surface properties and bioactivation of biomaterials on endothelial
      cells.
AB  - Interactions between vascular endothelial cells (EC) and materials are central to
      biomedical applications such as vascular graft endothelialization or
      vascularization of an engineered tissue substitute. To improve implant success,
      biomaterial surfaces are designed to modulate EC adhesion and responses. In vivo,
      EC line all blood vessels; their morphology, function and associated matrix are
      adapted to and specific for the local microenvironment. To enhance EC adhesion
      and growth, surface treatments have been developed that modify material surface
      physico-chemical and mechanical properties. Materials may also be coated with
      bioactive molecules such as proteins from the matrix, peptides and/or growth
      factors to study and control EC behaviour. The aim of this review is therefore to
      give an overview of current knowledge related to EC and their matrix environment
      in vivo and their responses to synthetic surfaces in vitro.

PMID- 20036945
TI  - Microbial polysaccharide: new insights for treating autoimmune diseases.
AB  - The immunosuppressive properties of Glucuronoxylomannnan (GXM), a purified
      capsular polysaccharide of the opportunistic fungus Cryptococcus neoformans, have
      been extensively elucidated. GXM can inhibit the function of cells belonging to
      both the innate and adaptive immune systems, leading to inhibition of
      proinflammatory responses as well as of autoimmune inflammation.This review
      focuses on the role of GXM as a novel anti-inflammatory agent and puts in
      perspective the direct implications of its potential destination to clinical
      trials.

PMID- 20036947
TI  - Biomarkers expression in rat olfactory ensheathing cells.
AB  - Olfactory Ensheathing Cells (OECs) ensheathe unmyelinated olfactory axons and
      exhibit antigenic and morphological characteristics both of astrocytes and of
      Schwann Cells (SCs). As a matter of fact they express an astrocyte-specific
      marker (GFAP) and low-affinity p75 nerve growth factor receptor (p75 NGFr), S100,
      as well as adhesion molecules such as laminin and N-CAM like SCs.
      Immunocytochemical studies reveal that OECs are able to produce different growth
      and survival factors. In vitro, OECs promote axonal growth, probably by secretion
      of neurotrophic growth factors that support axonal elongation and extension. In
      vivo studies have shown that OECs can form myelin promoting remyelination of
      damaged axons. In fact, when transplanted, they stimulate extensive sprouting and
      axonal regeneration of multiple axons. As OECs appear to exert a neuroprotective
      effect for functional restoration and for neural plasticity in neurodegenerative
      disorders, they might be considered a suitable approach to functional recovery.
      These data establish OECs as prime candidates for transplantation, showing some
      advantages over SC thanks to their different capacity to intermingle with
      astrocytes after implantation in lesion sites.

PMID- 20036948
TI  - Parathyroid hormone-related peptide and primary hyperparathyroidism.
AB  - The parathyroid hormone-related peptide (PTHrP) has been shown to be the major
      pathogenic factor to humoral hypercalcemia of malignancy (HHM). The presence of
      PTHrP in many normal tissues and in normal or abnormal parathyroids has been
      described in literature and its role has been investigated. PTHrP release from
      parathyroid cells into the extracellular space has been demonstrated to depend on
      the extracellular calcium concentration. The hormone binds to PTH type 1 Receptor
      (PTH1R) with a high affinity, as well as parathyroid hormone (PTH). These
      hormones' amino-terminal (1-34) peptide fragments are considered sufficient to
      achieve efficient receptor activation and action on mineral ion homeostasis.
      Generally, diagnosis of primary hyperparathyroidism (PHPT) is based on
      hypercalcaemia and elevated levels of PTH. The advent of intact-PTH
      immunoradiometric assay allowed us to distinguish PHPT from non-parathyroid
      dependent hypercalcaemia, but the presentation of normal PTH level and
      hypercalcaemia due to a parathyroid adenoma is possible. The aim of the study is
      to identify the relationship between the production of PTHrP without malignancy
      and the diagnosis of PHPT by a systematic review.

PMID- 20036949
TI  - Biochemical markers in Celiac disease.
AB  - Celiac Disease is a worldwide spread condition affecting 1:100-1:200 individuals.
      It is a permanent food intolerance to ingested gluten in genetically predisposed
      subjects. In this review we analyze the biochemical markers of the disease going
      from laboratory findings to histology passing through genetics. Gluten
      intolerance is a unique model of autoimmune disease in which we can recognize the
      main environmental factor (gluten) and the more complex genetic background. In
      additional way, serological markers for monitoring the disease and a safe and
      effective therapy (gluten free diet) are also available. In deed the
      environmental factor such as gluten intake is necessary to trigger the disease
      but genetics also matter. HLA genes are the most studied but in recent times also
      not HLA related genes are giving proof of additional relative risk to disease if
      present. From histological point of view intra epithelial cell infiltration by
      several lymphocyte subsets is becoming more and more important also for
      understanding pathogenesis of the disease.

PMID- 20036946
TI  - Brain plasticity in Diptera and Hymenoptera.
AB  - To mediate different types of behaviour, nervous systems need to coordinate the
      proper operation of their neural circuits as well as short- and long-term
      alterations that occur within those circuits. The latter ultimately devolve upon
      specific changes in neuronal structures, membrane properties and synaptic
      connections that are all examples of plasticity. This reorganization of the adult
      nervous system is shaped by internal and external influences both during
      development and adult maturation. In adults, behavioural experience is a major
      driving force of neuronal plasticity studied particularly in sensory systems. The
      range of adaptation depends on features that are important to a particular
      species, and is therefore specific, so that learning is essential for foraging in
      honeybees, while regenerative capacities are important in hemimetabolous insects
      with long appendages. Experience is usually effective during a critical period in
      early adult life, when neural function becomes tuned to future conditions in an
      insect's life. Tuning occur at all levels, in synaptic circuits, neuropile
      volumes, and behaviour. There are many examples, and this review incorporates
      only a select few, mainly those from Diptera and Hymenoptera.

PMID- 20036950
TI  - Natural polyphenols as anti-inflammatory agents.
AB  - Celiac Disease is a worldwide spread condition affecting 1:100-1:200 individuals.
      It is a permanent food intolerance to ingested gluten in genetically predisposed
      subjects. In this review we analyze the biochemical markers of the disease going
      from laboratory findings to histology passing through genetics. Gluten
      intolerance is a unique model of autoimmune disease in which we can recognize the
      main environmental factor (gluten) and the more complex genetic background. In
      additional way, serological markers for monitoring the disease and a safe and
      effective therapy (gluten free diet) are also available. In deed the
      environmental factor such as gluten intake is necessary to trigger the disease
      but genetics also matter. HLA genes are the most studied but in recent times also
      not HLA related genes are giving proof of additional relative risk to disease if
      present. From histological point of view intra epithelial cell infiltration by
      several lymphocyte subsets is becoming more and more important also for
      understanding pathogenesis of the disease.

PMID- 20036951
TI  - Biomarkers in neuroendocrine tumors.
AB  - Here, we review the role of clinical biomarkers (tissue and circulating markers)
      in the management of neuroendocrine tumors. These tumors may originate in
      different organs, from cells embriologically different but expressing common
      phenotypic characteristics, such as the immuno-reactivity for markers of neuro
      endocrine differentiation (defined as "pan-neuroendocrine"), the capacity to sec
      rete specific or aspecific peptide and hormones, and the expression of some
      receptors, that are at the basis of the current diagnostic and therapeutic
      approach.

PMID- 20036952
TI  - Bioclinical markers in breast cancer: updates and perspectives.
AB  - Molecular studies have definitely changed our knowledge of the biology of
      cancers, and breast cancer's tremendous social impact has stimulated a large mass
      of research. Classic markers have opened a road, but their usefulness appears
      limited to prognosis or follow up, while several new markers, both genetic and
      molecular, are assuming different, yet still controversial, importance: they may
      play a major role in the surveillance of subjects at risk, in detecting primary
      or recurrent cancers, and in predicting the need of adjuvant therapy, or the
      response to therapy. .

PMID- 20036953
TI  - Homocysteine, vitamin determinants and neurological diseases.
AB  - This review focuses on the putative role of hyper-homocysteinemia in the
      pathogenesis of different diseases affecting the nervous system, including
      stroke, Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis
      and amyotrophic lateral sclerosis. However, a firm pathogenic role of
      homocysteine in these diseases has never been established. Lowering plasma
      homocysteine levels trough vitamin therapy failed to prevent vascular diseases.
      Conversely, normalization of hyper-homocysteinemia caused improvement in patients
      with cognitive impairment. B vitamin deficiency is the main determinant of
      homocysteine levels. However, it has been hypothesized that homocysteine might be
      a mere marker of vitamin deficiency or an indicator of disease rather than a risk
      factor. A more consistent use of thresholds to define deficiency is needed to
      recommend routine screening, monitoring and supplementation of B vitamins to
      ameliorate the prognosis of the above mentioned disorders. To date, data are
      insufficient to firmly establish which one of the hypotheses made is correct and
      the question concerning the real meaning of hyper-homocysteinemia in the
      pathology of the nervous system still remains an intriguing medical dilemma.

PMID- 20036954
TI  - Biomarkers of myocardial injury after cardiac arrest or myocardial ischemia.
AB  - Outcomes of victims of cardiac arrest or acute myocardial ischemic events have
      improved with advances in medical therapy. Heart failure, however, remains a
      leading cause of morbidity and mortality after these conditions have occurred.
      Clinical features may be useful for predicting patients who are at risk of
      developing such complications, but they lack of sensitivity and specificity.
      Biomarkers have been therefore suggested as means to provide relevant prognostic
      information. The more commonly used biomarkers after cardiovascular ischemic
      events, including cardiac arrest, are creatin kinases and troponins. In addition,
      natriuretic peptides and C-reactive protein have gained great interest and now
      sufficient data has been collected such to justify their clinical applicability.
      Finally, several other novel biomarkers, to be used after resuscitation from
      cardiac arrest or more generally after a myocardial ischemic event, have been
      anticipated. Nevertheless, the "perfect" biomarker, able to provide diagnosis and
      prognosis with high sensitivity and specificity does not exit. A multimarker
      strategy that categorizes patients based on the number of elevated biomarkers at
      presentation is therefore suggested.

PMID- 20036955
TI  - Biomarkes of aging.
AB  - Ageing is a complex process that negatively impacts the development of the
      different systems and its ability to function. On the other hand, the rate of
      ageing in humans is not uniform, due to genetic heterogeneity and the influence
      of environmental factors. Thus, the ageing rate, measured as the decline of
      functional capacity and stress resistance, seems to be different in every
      individual. Therefore, attempts have been made to analyse this individual age,
      the so-called biological age, in comparison to chronological age. Age-related
      changes in body function or composition that could serve as a measure of
      biological age and predict the onset of age-related diseases and/or residual
      lifetime are termed biomarkers of ageing. Such biomarkers of ageing should help
      on the one hand to characterise this biological age and, as age is a major risk
      factor in many degenerative diseases, could be subsequently used on the other
      hand to identify individuals at high risk of developing age-associated diseases
      or disabilities. Unfortunately, most of the markers under discussion are related
      to age-related diseases rather than to age, so none of these markers discussed in
      literature is a true biomarker of ageing. Hence, we discuss some disease-related
      biomarkers useful for a better understanding of ageing and the development of new
      strategies to counteract it, essential for improving the quality of life of the
      elderly population. Biomarkers discussed are based on immunosenescence,
      inflammatory responses and oxidative stress, since the review is based on data
      from author laboratories rather than on an extensive review of the literature.
      However, this kind of knowledge is useful to anti-ageing strategies aimed to slow
      ageing and to postpone death by preventing infectious diseases and delaying the
      onset of age-related diseases.

PMID- 20036956
TI  - Clinical and biological markers in gastric cancer: update and perspectives.
AB  - Gastric cancer is the second cause of death from cancer worldwide and the only
      chance to reach better outcomes lays on an early diagnosis. The need for non
      invasive, low-cost tests is invoked also in countries in which imaging and
      endoscopic screening have already showed the ability to improve early diagnosis
      and overall survival. Genomic medicine could allow a better understanding of
      regulatory pathways driving the development and growth of gastric cancer and the
      characterization of specific molecular targets actually stimulate new drug
      developments. The knowledge of the role of Helicobacter pylori (HP) in gastric
      tumor pathogenesis has put new insides in the understanding of this peculiar
      disease and enriched the field of gastric biomarkers.

PMID- 20036957
TI  - Biomarkers in familial adenomatous polyposis: role and significance.
AB  - A biomarker, according to a generally accepted definition, is a substance or a
      manifestation used as indicator of a biologic state. It has the characteristic to
      be objectively measured and evaluated as an indicator of normal biologic
      processes, pathogenic processes, or pharmacological responses to therapeutic
      interventions. Biomarkers are important tools available to the clinicians with
      escalating perspectives in oncologic field. Clinical and genetic biomarkers are
      essential to properly individuate the disease, to address patients to specific
      surveillance programs and therapeutic strategies. An ideal biomarker should be
      absent in normal tissue/condition but present in precancerous lesions like
      dysplasia and so able to recognize early cancer. Coming from these
      considerations, several of the known genetic pathways in cancer pathogenesis
      could be considerate potential candidate biomarkers. In this review, we have
      reported clinical and molecular biomarkers helpful to manage the Familial
      Adenomatous Polyposis (FAP), a dominantly inherited colorectal cancer
      predisposition syndrome. Biomarkers, both clinical and molecular, are essential
      to reduce the high potential morbidity of FAP giving the opportunity to develop
      innovative diagnostic and therapeutic protocols.

PMID- 20036958
TI  - Biological and clinical markers in colorectal cancer: state of the art.
AB  - Colorectal cancer (CRC) is the World's third most common cancer. Its prognosis is
      closely related to the disease stage at the time of diagnosis. Here we review the
      role of clinical biomarkers (tissue, serum, and faecal) in the management of CRC.
      Molecular studies have recently widened the opportunity for testing new possible
      markers, but actually, only few markers can be recommended for practical use in
      clinic. In the next future the hope is to have a complete panel of clinical
      biomarkers to use in every setting of CRC disease, and at the same time: 1) to
      receive information about prognostic significance by their expression and 2) to
      be oriented in the choice of the adequate treatment.

PMID- 20036959
TI  - Increased EEG delta frequency corresponds to chorioamnionitis-related brain
      injury.
AB  - We evaluated the impact of chorioamnionitis on the intrapartal EEG delta
      frequency in the non-anesthetized preterm sheep. 10 mg intra-amniotic LPS or
      saline were given 2 or 14 days before preterm birth at gestational day 125. Lambs
      were delivered by Caesarean section under local anesthesia. A 5-minute EEG
      depicted delta activity and amplitude, and the relationship between EEG delta
      activity and both the white matter (WM) and cortical microglial activation and
      apoptosis was analyzed. EEG delta activity was increased significantly in the 14
      day LPS preterm fetuses compared to both preterm control and 2-day LPS animals (p
      less than 0.05). No differences were seen between controls and the 2-day LPS
      fetuses. A direct association was demonstrated between EEG delta activity and
      both cortical microglial activation (r = 0,645, p = 0,024) and apoptosis (r =
      0,580, p = 0,048), and between delta and WM activated microglia (r = 0,742, p =
      0,006) and apoptosis (r = 0,777, p = 0,003). This study is the first to show a
      relationship between brain dysfunction and chorioamnionitis-related injury at
      birth.

PMID- 20036960
TI  - Evolving treatments of virus-associated HCC: new targets and drugs.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignant tumors
      worldwide. The major etiologies and risk factors for HCC development are well
      defined and some of the multiple steps involved in hepatocarcinogenesis have been
      elucidated in recent years. The therapeutic options fall into five main
      categories: (1) surgical interventions, incl. liver transplantation, (2)
      percutaneous interventions, incl. ethanol injection and radiofrequency thermal
      ablation, (3) transarterial interventions, (4) radiation therapy and (5) drugs as
      well as gene and immune therapies. Because of the poor survival of the majority
      of patients, HCC prevention as well as early diagnosis and the development of
      novel systemic therapies for advanced disease are of paramount importance. In
      this context, recent data indicate that the 'targeted therapy' with monoclonal
      antibodies (mabs) or small molecule tyrosine kinase inhibitors (nibs) and other
      drugs seem to be effective to some degree. New technologies, including gene
      expression profiling and proteomic analyses, should allow to further elucidate
      the molecular events underlying HCC development and to identify novel diagnostic
      markers as well as therapeutic and preventive targets.

PMID- 20036961
TI  - Characterization of a three-drug nonlinear mixture response model.
AB  - Our group recently developed a response-surface modeling paradigm (White et al:
      Curr Drug Metab 2, 399-409, 2003) and tested its application to both mixtures of
      anticancer agents and antifungals. This new model is a Hill-type equation, with
      the slope and potency parameters being functions of the normalized drug ratios,
      using polynomial expressions. Response surface methods allow one to model and
      interpret all of the information present in the full concentration-effect data
      set, to visualize local regions of synergy, additivity and antagonism, and even
      to quantify the degree of synergy or antagonism, both globally, and across local
      regions of the response surface. In the present article, we study the effect of
      changes in the different parameters of the polynomial expressions for two-drug
      and three-drug mixtures, on the geometrical shapes of several 2-dimensional
      representations of the 3-dimensional concentration-effect surface. A secondary
      goal of this report is to compare the mathematical characteristics of the rival
      White and (Minto et al: Anesthesiol 92, 1603-1616, 2000) modeling paradigms.

PMID- 20036963
TI  - A review of synergy concepts of nonlinear blending and dose-reduction profiles.
AB  - This article presents a case-study review of synergy concepts of nonlinear
      blending and dose-reduction profiles. "Strong nonlinear blending" is a novel
      concept that provides a flexible paradigm for the assessment of combination drug
      synergy that is applicable to any shaped combination-drug dose-response surface;
      issues of varying relative potency, partial inhibitors, potentiation, or coalism
      pose no problems at all. Dose-reduction profiles are overlay plots created to
      show how much each drug can be reduced in amount and yet achieve the same
      efficacy as larger amounts of each drug used individually. This review applies
      these synergy concepts to two data sets from a previously published experiment.
      The previous publication had claimed a high degree of Loewe synergy for one of
      the data sets. However, a more penetrating analysis shows that with regard to
      strong nonlinear blending there is no reason to blend (for purposes of response
      enhancement) the two compounds studied. However, the dose-reduction profile plots
      show how Loewe synergy is present and provide further insight to the interaction
      of the two compounds (on the dose-concentration scale).

PMID- 20036962
TI  - Bone remodeling, humoral networks and smart biomaterial technology for
      osteoporosis.
AB  - One of the unfortunate sequelae of increased life expectancy is a growing number
      of age-related degenerative diseases, a prime example being osteoporosis. This
      form of metabolic bone disease and related co-morbidities consume tremendous
      resources and costs from a nation's health care system. Osteoporosis results from
      genetic, age-related, and hormone-dependent causes as well as a compendium of
      secondary pathophysiological states. The presence of osteoporosis as a
      comorbidity confers a significant negative prognostic element following
      orthopedic procedures. In vitro and in vivo studies of osteoporotic bone
      implicate microarchitectural bone rarefaction, microenvironmental and functional
      disturbance of osteoblast-osteoclast coupling, and abnormal tissue and signalling
      molecule repertoires, each having detrimental effects on the regenerative and
      osteointegration processes. This review explores the pathophysiology of bone
      remodeling from a macro- and micro- systems biology standpoint with a focus on
      cytokine interactions. Furthermore, therapeutic interventions exploiting
      vulnerable nodes in these physiological networks will be posited. One exciting
      development in this area is the use of novel biomaterials.

PMID- 20036964
TI  - Chemoattractants and receptors in Alzheimer's disease.
AB  - Chemoattractants, including classical chemoattractants and chemokines, are
      mediators of leukocyte trafficking in physiological immunosurveillance as well as
      recruitment of leukocyte to the sites of inflammation and injury. Besides their
      well-established role in the immune system, recent researches have demonstrated
      that chemoattractants and their receptors are also involved in brain development
      and in the maintenance of normal brain homeostasis. Evidence is emerging that
      chemoattractants and their receptors play important roles in neuroinflammation,
      neuronal death and hence neurodegenerative diseases. In this review, we summarize
      recent progress regarding the involvement of chemoattractants and their receptors
      in Alzheimer's disease and their potential as therapeutic targets.

PMID- 20036965
TI  - Acetyl-CoA carboxylase-a as a novel target for cancer therapy.
AB  - Acetyl-CoA carboxylases (ACC) are rate-limiting enzymes in de novo fatty acid
      synthesis, catalyzing ATP-dependent carboxylation of acetyl-CoA to form malonyl
      CoA. Malonyl-CoA is a critical bi-functional molecule, i.e., a substrate of fatty
      acid synthase (FAS) for acyl chain elongation (fatty acid synthesis) and an
      inhibitor of carnitine palmitoyltransferase I (CPT-I) for fatty acid beta
      oxidation. Two ACC isoforms have been identified in mammals, i.e. ACC-alpha
      (ACCA, also termed ACC1) and ACC-beta (ACCB, also designated ACC2). ACC has long
      been used as a target for the management of metabolic diseases, such as obesity
      and metabolic syndrome, and various inhibitors have been developed in clinical
      trials. Recently, ACCA up-regulation has been recognized in multiple human
      cancers, promoting lipogenesis to meet the need of cancer cells for rapid growth
      and proliferation. Therefore, ACCA might be effective as a potent target for
      cancer intervention, and the inhibitors developed for the treatment of metabolic
      diseases would be potential therapeutic agents for cancer therapy. This review
      summarizes our recent findings and updates the current understanding of the ACCA
      with focus on cancer research.

PMID- 20036966
TI  - Role of surfactant protein A and D (SP-A and SP-D) in human antiviral host
      defense.
AB  - SP-A and SP-D contribute to host defense against respiratory viral infection. The
      most extensive body of evidence relates to influenza A viruses (IAV), and
      evidence from gene-deleted mice also indicate a role for surfactant collectins in
      defense against respiratory syncytial virus (RSV) and adenovirus. Some important
      respiratory pathogens including rhinovirus and metapneumovirus have not yet been
      examined. Viral pathogens that enter the body via the respiratory tract (e.g.,
      Ebola virus), replicate in the lung (e.g., human immunodeficiency virus or HIV)
      or infect the lung in immuno-compromised hosts (e.g., herpes simplex virus or
      HSV) are inhibited by collectins. SP-A and SP-D are expressed in other mucosal
      surfaces (e.g., the eye or genitourinary tract) where they may play roles in
      antiviral defense. In addition to direct antiviral activities, the SP-A and SP-D
      modulate innate and adaptive immunity and inflammation associated with infection.
      The relative importance of antiviral vs anti-inflammatory effects of SP-A and SP
      D in viral infections and the potential use of these collectins as therapeutics
      for viral infections are under investigation.

PMID- 20036968
TI  - Biomarkers of glial cell proliferation and differentiation in culture.
AB  - The two major intermediate filament (IF) proteins of astrocytes are vimentin and
      GFAP. Early during development, radial glia and immature astrocytes express
      mainly vimentin. Towards the end of gestation, a switch occurs whereby vimentin
      is progressively replaced by GFAP in differentiated astroglial cells. The
      expression of vimentin and GFAP increased markedly after injury to CNS. GFAP has
      been widely recognized as an astrocyte differentiation marker, constituting the
      major IF protein of mature astrocyte. In our recent researches we investigated
      the interactions between growth factors and dexamethasone on cytoskeletal
      proteins GFAP and vimentin expression under different experimental conditions. In
      addition, nestin, a currently used marker of neural stem cells, is transiently co
      expressed with GFAP during development and is induced in reactive astrocytes
      following brain injury. The role of S100B in astrocytes, neurons, and microglia
      is particularly studied in Alzheimer's disease. In conclusion, such glial
      biomarkers will help us to understand the more general mechanisms involved in CNS
      development and can open new perspectives for the control of the neurologic
      diseases.

PMID- 20036967
TI  - Deregulation of RGS2 in cardiovascular diseases.
AB  - Alteration of G protein-coupled receptor (GPCR) signaling is a salient feature of
      hypertension and the associated heart diseases. Recent studies have revealed a
      large family of Regulators of G-protein Signaling (RGS) proteins as important
      endogenous regulators of GPCR signaling. RGS2 selectively regulates Galphaq/11
      signaling, an essential cause of hypertension and cardiac hypertrophy. Both
      clinical and animal studies have shown that deregulation of RGS2 leads to
      exacerbated Galphaq/11 signaling. There is an inverse correlation between RGS2
      expression and blood pressure, as well as a selective down-regulation of RGS2 in
      various models of cardiac hypertrophy. The causal relationship has been
      established in animal studies. RGS2 knockout mice exhibit not only hypertension
      phenotype but also accelerated cardiac hypertrophy and heart failure in response
      to pressure-overload. Further in vitro studies have shown that RGS2 knockdown
      with RNA interference exacerbates, whilst RGS2 over-expression completely
      abolishes the Galphaq/11-induced hypertrophy. These findings indicate that
      deregulation of RGS2 plays a crucial role in the pathogenesis of cardiovascular
      diseases, marking RGS2 as a potential therapeutic target or biomarker of
      hypertension or hypertensive heart diseases.

PMID- 20036969
TI  - Clinical biomarkers in hepatocellular carcinoma (HCC).
AB  - The Authors make a review of the most important molecules used today for
      detecting and screening hepatocellular carcinoma, analyzing their known
      biological features, advantages and limits especially concerning differential
      diagnosis from cirrhosis and others diseases. AFP, AFP-L3, DCP, Alpha-1
      fucosidase are analyzed and all the current knowledge reviewed, as well as
      focusing on possible future applications and results of combined determination
      (what about another word here: evaluation etc) in HCC. Additionally other more
      recent molecules showing promising future clinical application are cited.

PMID- 20036970
TI  - Molecular diagnosis of pancreatic cancer: where do we stand?
AB  - Pancreatic cancer remains a disease with a dismal prognosis due mostly to its
      late diagnosis. An early diagnosis would have a significant impact on the
      prognosis and, eventually, on the incidence of the disease itself. Many
      progresses have been made in the molecular diagnosis of pancreatic cancer. High
      risk patients would likely benefits from biologic screening, before the general
      population. Most of the markers remain limited to phase I and II studies. The
      challenges include the lack of specificity of some of the markers, as well as the
      lack of standardization within the laboratories. Further research is necessary
      prior to the application of the currently known biomarkers for the diagnosis of
      pancreatic cancer.

PMID- 20036971
TI  - Clinical biomarkers in kidney diseases.
AB  - Biomarkers are "biological parameters that can be objectively measured and
      evaluated, which act as indicators of normal or pathogenic processes, or of the
      pharmacological response to a therapeutic intervention". Renal failure can be
      broadly divided in acute and chronic renal diseases, two classes of renal
      pathology that are well distinct each other, not only on the basis of duration
      and reversibility of loss of kidney function, but also because of their different
      aetiopathological processes and their different histopathological
      characteristics. Unlikely, the conventional measures used for monitoring kidney
      function are not ideal in the diagnosis of neither acute or chronic kidney
      diseases and has impaired our ability to institute potentially effective
      therapies.Therefore, researchers are seeking new early, predictive, non-invasive
      biomarkers that can aid in the diagnosis for both acute and chronic
      diseases.These biomarkers will be useful for assessing the duration and severity
      of kidney disease, and for predicting progression and adverse clinical
      outcomes.This review article summarized our current understanding of the acute
      and chronic renal diseases and discussed the most promising biomarkers for
      facilitating early detection and predicting clinical outcomes.

PMID- 20036972
TI  - Genetic risk factors and candidate biomarkers for Alzheimer's disease.
AB  - Alzheimer's disease is a multifactorial and progressive neurodegenerative
      disease, extremely diffused and with an increasing prevalence worldwide. There is
      an urgent need for biomarkers to diagnose AD early in its course. Furthermore,
      accurate biomarkers would be able to determine the clinical efficacy of novel
      neuroprotective strategies. Although the heritability of late-onset AD is high,
      our knowledge of the underlying putative susceptibility genes remains incomplete
      and the only unequivocally established late-onset AD gene is APOE. Nevertheless a
      number of susceptibility loci seems to influence the pathogenesis of AD, and
      variations in numerous genes have been considered to be important in the risk for
      AD. Many advances have been made in identifying biochemical indices of brain
      dysfunction, measured in body fluids such as cerebrospinal fluid and plasma, with
      different methodological approaches. Although these biomarkers are promising,
      none of them can predict AD with 100% confidence to date. This review will
      elaborate on the available selection of genetic and biochemical biomarkers for
      AD, with a particular reference to those linked to inflammation and oxidative
      stress.

PMID- 20036973
TI  - Clinical biomarkers in brain injury: a lesson from cardiac arrest.
AB  - Cardiac arrest (CA) is the primary cause of death in industrialized countries.
      Successful resuscitation rate is estimated of about 40%, but a good neurological
      outcome remains difficult to achieve. The majority of resuscitated victims
      suffers of a pathophysiological entity termed as "post resuscitation disease".
      Today's efforts are mainly pointed to the chain of survival, often devoting less
      attention to post-resuscitation care. Resuscitated patients are often victims of
      nihilistic therapeutic approach, with clinicians failing to promptly institute
      strategies that mitigate the ischemia-reperfusion injury to vital organs. Only
      after 72 hours prognostication can be realistically attempted. Neurological
      evaluation relies on a combination of clinical, instrumental and laboratoristic
      parameters, since no one alone holds a specificity of 100%. Biochemical markers,
      such as neuron specific enolase and S-100b, may contribute to predict prognosis
      after CA. To the contrary, when used individually the necessary precision remains
      poorly characterized. Biochemical studies suffer from substantial methodological
      differences hampering attempts to summarize their findings. We review the
      information available on biochemical markers of brain damage for neurological
      prognostication after CA.

PMID- 20036974
TI  - Cardiac stem and progenitor cell identification: different markers for the same
      cell?
AB  - For a long time the heart has been considered a terminally differentiated organ
      without any regenerative potential. The latter has been classically based on the
      terminally differentiated nature of cardiomyocytes and the absence of a pool of
      tissue-specific stem cells. This view has been radically changed due to the
      discovery of resident cardiac stem and progenitor cells in the adult mammalian
      heart. However, at minimum, 5 apparently different cardiac stem and/or progenitor
      cell types have been described so far. Thus, we have changed from a view of the
      heart as a static tissue to an organ with the highest number of tissue-specific
      stem cell populations. Most likely, the different putative adult cardiac stem and
      progenitor cells represent different developmental and/or physiological stages of
      a unique resident adult cardiac stem cell. Notably, it is not yet known the
      origin of all these cells. A better understanding of the origin, biology and
      physiology of the myocardial stem and progenitor cells will impact the
      development of regenerative medicine as an effective therapy for heart disease
      and failure.

PMID- 20036975
TI  - Genetic polymorphisms in dilated cardiomyopathy.
AB  - Dilated cardiomypathies (DCM) are characterized by dilatation and pump
      dysfunction of the heart. DCM has an incidence of 6/100.000 people a year
      contributing to a considerable number of cases of heart failure. Although
      etiology and pathogenesis are known to be multifactorial, they remain mostly
      unidentified. Recent research identified patients affected with DCM with altered
      gene products. These alterations can roughly be grouped into causative genes,
      mostly coding for cytoskeletal proteins. Other genes seem to be activated after
      the disease onset and are able to influence the clinical course. In this study we
      systematically analyzed the role of genetic polymorphisms, based on peer-reviewed
      articles, published in scientific journals. A total of 97 original studies and a
      selected number of 60 genes, that seem to be related to DCM, have been reviewed.

PMID- 20036976
TI  - Novel biomarkers and therapeutic targets for prostate cancer.
AB  - Prostate cancer is the most prevalent cancer in the Western male population and
      the second leading cause of cancer death in men, affecting over 10 million
      individuals. Present approaches to control the cancer mortality have focused on
      the detection of the cancer at early stages when it is still locally confined and
      may be curable. Identification of the prostate-specific antigen (PSA) has
      facilitated the early diagnosis of prostate cancer. However, PSA has limited
      specificity and sensitivity in appropriately detecting early stages of abnormal
      prostate growth. PSA levels fail to differentiate between indolent and aggressive
      cancers, do not correlate with tumor size, and cross-react with other serine
      proteases namely, glandular kallikreins 1 and 2. Besides cancer, its levels also
      increase in men with benign prostatic hyperplasia (BPH), prostatitis, and other
      non-malignancies. Additional prostate-specific genes and metabolites need to be
      identified to provide a better understanding of the molecular mechanisms of
      prostate physiology and pathophysiology. Novel markers for the diagnosis and
      development of new treatment modalities are urgently needed.

PMID- 20036978
TI  - Novel aspects for the application of Curcumin in chemoprevention of various
      cancers.
AB  - Chemoprevention of malignant tumor growth is a novel and potentially powerful
      approach for tumor therapy. Recent in vitro and in vivo investigations provide
      increasing evidence that naturally occurring substances may exhibit significant
      chemopreventive activities. To this regard, the spice Curcumin, widely used in
      Indian cuisine, has been identified to show considerable anti-tumor effects. Most
      interestingly, numerous studies have not shown toxic side effects of this
      substance. Curcumin induces tumor cell apoptosis along with a reduction of tumor
      cell invasion and metastasis. Recent molecular studies provide evidence that
      Curcumin acts via a control of the NFkappaB pathway exerting most of the various
      modulating and moderating effects on malignant cells. Along with these in vitro
      studies, ex vivo and first clinical investigations confirm the anti-tumor effects
      of Curcumin, either as an isolated chemoprevention substance or in combination
      with chemotherapeutic agents as supportive measure reducing pharmaceutical
      resistance of tumor cells to certain chemotherapeutics. Despite our increasing
      knowledge on this interesting substance there still remain many unknown effects
      that deserve intense investigation.

PMID- 20036979
TI  - Toll-like receptor-mediated recognition of herpes simplex virus.
AB  - Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2, respectively) are two
      important human pathogens that belong to the genus simplex within the subfamily
      alpha of the Herpesvirinae. Toll-like receptors (TLRs) constitute a family of
      conserved sensors that play a prominent role during the early anti-viral
      response, including that against herpesviruses. Although substantial progress has
      been made, central questions remain to be solved to figure out how TLRs modulate
      viral pathogenesis. The aim of the present report is to review the current
      knowledge about TLR recognition and signaling of herpesviruses, focusing on HSV
      infection. The relative contribution of the TLR-mediated immune responses to
      antiviral immunity versus viral pathogenesis will be discussed as well.

PMID- 20036977
TI  - Mechanisms and controllers of eccrine sweating in humans.
AB  - Human body temperature is regulated within a very narrow range. When exposed to
      hyperthermic conditions, via environmental factors and/or increased metabolism,
      heat dissipation becomes vital for survival. In humans, the primary mechanism of
      heat dissipation, particularly when ambient temperature is higher than skin
      temperature, is evaporative heat loss secondary to sweat secretion from eccrine
      glands. While the primary controller of sweating is the integration between
      internal and skin temperatures, a number of non-thermal factors modulate the
      sweating response. In addition to summarizing the current understanding of the
      neural pathways from the brain to the sweat gland, as well as responses at the
      sweat gland, this review will highlight findings pertaining to studies of
      proposed non-thermal modifiers of sweating, namely, exercise, baroreceptor
      loading state, and body fluid status. Information from these studies not only
      provides important insight pertaining to the basic mechanisms of sweating, but
      also perhaps could be useful towards a greater understanding of potential
      mechanisms and consequences of disease states as well as aging in altering
      sweating responses and thus temperature regulation.

PMID- 20036980
TI  - Temperature control of spermatogenesis and prospect of male contraception.
AB  - Artificial cryptorchidism or local testicular heat treatment could induce
      reversible oligospermia or azoospermia in monkeys via germ cell apoptosis. A
      single exposure of rat or monkey testes at 43 degrees centigrade resulted in
      selective and reversible damage to seminiferous epithelium. Local warming monkey
      testes at 43 degrees centigrade water for consecutive two days (30 minutes per
      day) showed that the sperm amount in the semen decreased up to 80% at 28 days and
      is completely reversible. Furthermore, the heat treatment in combination with
      testosterone, the sperm account reduced to zero in 2 month time. Withdrawing the
      testosterone implant, the density of semen sperms recovered to the normal levels
      after 2-3 months. Apoptosis induced by testosterone occurs mainly at stages 7-8,
      while testicular "heat stress" induces germ cell apoptosis mostly at stages 1- 4
      and 10-12, an additive reversible germ cell apoptosis could be achieved. These
      findings have provided an important theoretical basis for designing combined male
      contraceptives. This present review summarized progress on the mechanism of heat
      induced germ cell apoptosis.

PMID- 20036981
TI  - Primary and secondary prevention of liver cancer caused by HBV.
AB  - Primary cancer of the liver (hepatocellular carcinoma, HCC) is one of the most
      common cancers worldwide; HBV is the major cause of HCC. A vaccine that protects
      against HBV infection was invented in 1969 and is now one of the most commonly
      used vaccines. National vaccination programs have dramatically reduced the
      prevalence of HBV infection and carriers, with a concomitant decrease in the
      incidence of HCC in the vaccine-impacted populations. HBV vaccine is the first
      widely used cancer prevention vaccine; a second that protects against papilloma
      virus and cancer of the cervix has recently been introduced. Appropriate
      treatment of HBV carriers with antivirals can reduce the titers of HBV in their
      blood and thereby greatly reduce the risk of HCC and chronic liver disease.
      Further data are required to establish criterion for treatment to enable
      protocols for medical and prevention programs. There are other viral caused
      cancers and an understanding of their pathogenesis is an important future
      direction for research to reduce the human burden of cancer.

PMID- 20036982
TI  - Functional and comparative assessments of the octopus learning and memory system.
AB  - The octopus and its close relatives the cuttlefish and squid are the most
      advanced of the invertebrates, possessing the largest brains both in weight and
      cell numbers. Here I review recent studies of the neurophysiological properties
      of the vertical lobe system (VL) in the cephalopod brain, a system already
      thought to be dedicated to learning and memory. Summarizing from the point of
      view of comparative evolution, I relate these results to other systems where
      anatomical and electrophysiological data are available, mainly the insect
      mushroom bodies and the mammalian hippocampus. The emerging results suggest that
      a convergent evolutionary process has resulted in similar neural organization and
      activity-dependent long-term synaptic plasticity in all these learning and memory
      systems, even though the invertebrate systems conserve their typical anatomical
      and electrophysiological features. And finally, functional inferences based on
      the comparison with the insect mushroom.

PMID- 20036983
TI  - Kappa2 opioid receptor subtype binding requires the presence of the DOR-1 gene.
AB  - Over the past several years substantial evidence has documented that opioid
      receptor homo- and heterodimers form in cell lines expressing one or more of the
      opioid receptors. We used opioid receptor knockout mice to determine whether in
      vivo pharmacological characteristics of kappa1 and kappa2 opioid receptors
      changed following knockout of specific opioid receptors. Using displacement of
      the general opioid ligand diprenorphine, we observed that occupancy or knockout
      of the DOR-1 gene increases the binding density of kappa1 receptors and
      eliminates kappa2 receptors in crude membrane preparations while the total
      density of kappa opioid binding sites is unchanged. Further, the analgesic
      potency of U69,593 in cumulative dose response curves is enhanced in mice lacking
      the DOR-1 gene. These results demonstrate that the DOR-1 gene is required for the
      expression of the kappa2 opioid receptor subtype and are consistent with the
      possibility that a KOR-1/DOR-1 heterodimer mediates kappa2 pharmacology.

PMID- 20036984
TI  - Brain apoptosis and carotid artery reactivity in fetal asphyctic preconditioning.
AB  - We aimed to develop a model of fetal hypoxia-ischemia (HI) preconditioning that
      reflects the pathophysiological conditions of perinatal asphyxia more closely
      than the existing neonatal stroke models. Fetal asphyxia (FA) was induced by
      clamping the uterine vasculature on embryonic day E17. At birth (P0), severe
      perinatal asphyxia (SPA) was induced during cesarean section. At P4, carotid
      arteries were studied in a wire myograph and at P8 brains were analyzed for
      apoptotic cell death in the prefrontal cortex and striatum. The contraction
      induced by K+ was significantly reduced in the carotid arteries from the SPA
      group and endothelium-dependent relaxation (mediated by acetylcholine) was
      augmented in the FA group. These changes in vascular responsiveness were not
      present in the animals exposed to both insults (FA + SPA). Additionally, FA+SPA
      animals showed lower numbers of apoptotic cells compared to SPA animals in both
      the prefrontal cortex and striatum. Exposure to a global fetal asphyctic insult
      seems to protect against the vascular alterations and the increase of apoptosis
      in striatum and prefrontal cortex induced by severe asphyxia at birth.

PMID- 20036985
TI  - Broad-spectrum and virus-specific nucleic acid-based antivirals against
      influenza.
AB  - Rapid increase in drug-resistant influenza virus isolates, and pandemic threat
      posed by highly pathogenic avian influenza A and swine flu viruses provide clear
      and compelling reasons for fast tracking development of novel antiviral drugs.
      Nucleic acid-based drugs represent a promising class of novel antiviral agents
      that can be designed to target various seasonal, pandemic and avian influenza
      viruses. Nucleic acids can be designed to elicit broad-spectrum antiviral
      responses in the host, by suppressing viral gene expression, or by inducing
      cleavage or degradation of viral RNA. Immunomodulating nucleic acids, such as
      double stranded RNA and CpG oligonucleotides, can be potent anti-influenza agents
      that work by eliciting protective innate and adaptive immunity in the host. By
      activating the toll-like receptor signaling pathways, these drugs can activate
      the host's antiviral and inflammatory defenses to combat influenza viruses.
      Antisense oligonucleotides, small interfering RNAs (siRNA), and nanoRNAs
      represent sequence specific gene-silencing approaches that could be deployed to
      suppress or inhibit viral protein gene expression. Lastly, catalytic nucleic
      acids such as DNAzymes and/or ribozymes can suppress viral replication by
      repeatedly cleaving viral mRNAs and template RNAs. In summary, nucleic acid-based
      antiviral agents are versatile, diverse and could complement existing antiviral
      drugs in combating influenza.

PMID- 20037004
TI  - Notes from the editors.

PMID- 20037003
TI  - Ad hoc reviewers for the journal of motor behavior.

PMID- 20037005
TI  - Correlates of recurrent falling in independent community-dwelling older adults.
AB  - This study compared the ability of selected measures of vision, health, physical
      activity and performance, and fall history to predict the risk of recurrent falls
      in independent community-dwelling older adults. Of particular interest was the
      association between visual field (VF) constriction and falling. Age-related VF
      constriction is well documented and is known to accelerate in persons over age
      55. Although several authors have implied that VF constriction in older adults
      could contribute to instability and falls, there has been no attempt to
      systematically examine this relationship. A battery of tests were administered to
      men and women (N = 96) 60-88 years of age. Falls were closely monitored for 1
      year following the testing. Fifty of the 96 participants (52%) fell during the 1
      year monitoring period, amassing a total of 91 falls, 5 of which resulted in
      fractures. There were 46 nonfallers, 27 one-time fallers, and 23 recurrent
      fallers. A stepwise logistic regression analysis revealed that average VF
      constriction, use of eyeglasses, and low systolic blood pressure were
      independently associated with recurrent falling. On discriminant function
      analysis, these 3 variables predicted status as a recurrent faller correctly in
      48% of cases, and predicted nonfaller status correctly in 93% of cases. The
      overall performance of the model was 70%. Hypotheses are offered for how average
      VF constriction, use of eyeglasses, and low systolic blood pressure could
      influence stability and fall risk in older adults.

PMID- 20037006
TI  - Diminishing the effects of reduced frequency of knowledge of results on
      generalized motor program learning.
AB  - Several recent studies have shown that, compared with presenting knowledge of
      results (KR) on every practice trial, withholding KR on some practice trials
      enhances the learning of generalized motor programs (GMPs; Wulf, Lee, & Schmidt,
      1994; Wulf & Schmidt, 1989; Wulf, Schmidt, & Deubel, 1993). In this study,
      whether this effect may result from an uncertainty on the part of participants
      about when KR is to be presented was determined by examining the GMP learning of
      two 67% relative-frequency KR groups-one that received advance information
      regarding the delivery of each KR (67% AKR) during practice trials and another
      that received no advance information (67% KR)-as well as that of a 100% KR group.
      The task required participants to produce 3 movement patterns that shared the
      same relative and absolute timing and relative amplitude but differed in terms of
      absolute amplitude. KR was provided by displaying the root-mean-square error
      (RMSE) score and by graphically superimposing the participant-produced pattern on
      that of the goal movement. The results revealed no group differences in measures
      of GMP development or parameterization effectiveness during practice and no-KR
      retention. However, during no-KR transfer with a novel absolute amplitude, the
      67% KR group demonstrated a more accurate and stable GMP than the 67% AKR and
      100% KR groups. Possible explanations for why advance knowledge about KR delivery
      diminishes GMP development are discussed.

PMID- 20037007
TI  - On the effectiveness of force application in guided leg movements.
AB  - In guided leg movements (e.g., in cycling or wheelchair propulsion), the
      kinematics of a limb are determined by the object on which a force is applied. As
      a consequence, the force direction can vary and may deviate from the movement
      direction, that is, the effective direction. In the present study, the relation
      of effective force application and maximal power output was examined. Subjects (n
      = 5) performed guided leg tasks on a special dynamometer. They were instructed to
      exert a maximal force against a moving forceplate in the direction of the
      movement, as if they were pushing the plate away. Three different movement
      directions were tested: perpendicular to the horizontal, rotated 30 degrees
      backward, and rotated 30 degrees forward. For each trial, force and position data
      were recorded. The results of the experiments showed that in the extreme movement
      directions (both 30 degrees conditions), the force vector deviated significantly
      from the direction of the movement. Apparently, maximal power output was achieved
      with a low force effectiveness in these tasks. The background of this phenomenon
      was revealed by using the kinematics of one of these tasks in a simulation model.
      The stimulation level of 6 leg muscles was optimized toward a maximal effective
      force component (a) without a constraint on the direction of the total force or
      (b) with a constraint on the force component perpendicular to the effective
      force. The muscle stimulation pattern that resulted in the highest effective
      force coincided with a low force effectiveness. Apparently, this is a
      prerequisite for maximal power transfer from the muscles to the plate in these
      guided movements.

PMID- 20037008
TI  - Delayed auditory feedback in synchronization.
AB  - In two experiments, the effect of feedback delay on synchronization performance
      was examined. In Experiment 1, whether feedback delay has an effect on the
      asynchrony between tap and click was investigated, and a transfer effect between
      conditions, observed in a preliminary experiment, was studied. Experiment 2
      served as a control experiment that assured that the effects were not caused by
      order effects. A linear relationship between the size of the delay and the
      asynchrony between tap and click was observed; that is, with increasing delay,
      the size of the asynchrony increased as well. The results support an extended
      version of the Paillard-Fraisse hypothesis that accounts for the results observed
      in synchronization tasks in which more than a single source of feedback from the
      tap is available. The results indicate that all tap-related information is
      integrated into a joint event code representing that tap at a central level.
      These codes are superimposed on click-related codes and are therefore responsible
      for the observed asynchronies. Moreover, the results suggest that tap-related
      codes arise from a linear combination of their tactile-kinesthetic and auditory
      components.

PMID- 20037009
TI  - Control of human arm movements in two dimensions: influence of pointer length on
      obstacle avoidance.
AB  - Human subjects (N = 13) made arm movements in a horizontal plane by using the
      shoulder, elbow, and wrist to move a pointer to a target while avoiding simple
      obstacles. Movements with no pointer and with pointers of three different lengths
      were tested so that the lever arm of the wrist could be changed and its effective
      redundancy altered. With increasing pointer length, movement durations decreased,
      wrist movement used in avoiding obstacles increased, and variability in proximal
      joint angles increased. Most characteristics of paths and joint movements
      previously described for movements with the long pointer were found to generalize
      to movements with shorter pointers or with no pointer-the condition used in
      several previous comparisons of 2- and 3-joint movements. Both joint angles and
      path parameters changed in accommodating to the constraints added by obstacles
      and by increasing pointer length, implying that criteria defined in workspace and
      in joint space together influence paths in workspace and joint movement, as
      postulated by bidirectional models. Increased wrist extension and flexion during
      movement, compared with static pointing, indicate that dynamic factors are also
      important.

PMID- 20037010
TI  - A method for calculating the circularity of movement trajectories.
AB  - A method for computing the circularity of any closed two-dimensional trajectory
      of arbitrary shape is described. The core of this technique is the derivation of
      moments of area for each closed contour defined by perimeter coordinates. The
      method can be used to analyze two-dimensional data of any form, and provides
      output information including the number of closed contours within the data set,
      the area of each contour, the position of the centroid of each contour, the
      orientation of each contour, and the parameters of the ellipse that best fits
      each contour. A number of applications are discussed, including the comparison of
      kinematic trajectories, the calculation of cross-sectional areas from digitized
      MRI scans, and the analysis of phase portraits.

PMID- 20037011
TI  - A functional analysis of human mirror movements.
AB  - In this report, an experimental method for investigating the effect of variations
      in force, amplitude, and frequency of oscillations of the isometric pincer grasp
      on mirror movements (MM) is described. Normal adults (N = 24) were used as
      experimental subjects. The magnitude of MM was greater at relatively high static
      force levels maintained by the passive hand (26% of maximum volitional force or
      MVF) than at low force levels (4% MVF) in the passive hand. By contrast, the
      magnitude of MM was smaller at relatively large (20.5% MVF) than at small (9.5%
      MVF) mean force levels of the active hand when the static force in the passive
      hand as well as the amplitude and range of oscillation frequencies of the active
      hand were held constant. The magnitude of MM relative to active hand oscillation
      was smaller when the active hand oscillated around a relatively large amplitude
      (22% of MVF) than when it did so around a small amplitude (8% of MVF) at constant
      mean force levels and oscillation frequencies. The absolute magnitude of MM was
      not affected by this change in oscillation amplitude. In all experiments, the
      magnitude of MM was consistently less at relatively high than at low frequencies
      of oscillation in the active hand. Intrinsic variables of motor control have a
      major effect on the inducation and modulation of MM, and their contribution may
      be as great as that of subject variables. The present results differed
      substantially from those of others who have used similar experimental paradigms.
      The major difference was the direction of change in power transfer from the
      active to the passive hand with changes of force in the active hand. Possible
      reasons for these differences are discussed.

PMID- 20037012
TI  - Editorial policy and instructions for authors.

PMID- 20037013
TI  - Editorial policy and instructions for authors.

PMID- 20037014
TI  - Index for volume 29.

PMID- 20037015
TI  - 1997 ad hoc reviewers for the journal of motor behavior.

PMID- 20037016
TI  - Nonvisible perception of segments of a hand-held object and the attitude spinor.
AB  - When a rod is grasped at a place intermediate between its ends, the nonvisible
      perception of length by wielding can be directed to either side of the hand. The
      selective perception of the lengths of rod segments relative to the hand is
      hypothesized to depend jointly on the rod's inertia tensor about a fixed rotation
      point and on the 2-valued attitude spinor connecting the rod's reference frame to
      the hand's. That hypothesis was tested in 3 experiments m which 8-10 subjects
      participated; asymmetry in the rod's mass distribution relative to the hand was
      induced either by the addition of a metal ring to one end or by grasping the rod
      at a place other than its midpoint. Planes of wielding, style of wielding, and
      object size were varied across the experiments. The results conformed to
      expectation: For a given asymmetric rod configuration, perceived length for
      attending to one direction from the hand (e g., above or left) differed from
      perceived length for attending to the other direction (below or right); for a
      given segment of an asymmetric rod, perception of its length did not differ as a
      function of us direction from the hand. In each experiment, variance in perceived
      partial length was accommodated by the rod's major eigenvalue and the spinor
      rotation angle, with rotation sense dictated by the direction of attention.

PMID- 20037017
TI  - Effects of repetitive lifting on kinematics: inadequate anticipatory control or
      adaptive changes?
AB  - In the present study, the effects of repetition on the kinematics in discrete
      lifting were studied in 10 subjects who lifted a barbell weighing 10% of body
      mass at a determined speed and along a determined trajectory 630 times during
      about 40 min. Three-dimensional (3-D) kinematics of the feet, lower and upper
      legs, pelvis, and trunk were recorded in the first 3 and the final 3 lifting
      movements of each set of 70 lifts. Over time, trunk extension velocity in the
      initial 250 ms of the lifting movement decreased, reaching negative (increasing
      flexion) values in most subjects. In contrast, hip extension velocity increased.
      Those changes resulted in an increased phase lag between hip and trunk extension.
      Also, over time, subjects started the lifting movement with their legs more
      extended and their trunks further flexed. Finally, the motion of the trunk around
      its longitudinal axis (twisting) increased. The increase in phase lag between hip
      and trunk extension is interpreted as a consequence of fatigue-more specifically,
      as the result of a decreased rate of force development of the back muscles. The
      change in initial posture more likely is an adaptation that functions to retard
      further fatigue development.

PMID- 20037018
TI  - The Rowing Cycle: Sources of Variance and Invariance in Ergometer and On-the
      Water Performance.
AB  - In a recent study of the kinematics of the drive phase of the rowing stroke, Lamb
      (1989) provided detailed evidence that ergometer performance simulates on-the
      water performance closely. In the present experiment, Lamb's analysis was
      extended in an investigation of the timing of the complete cycle of the rowing
      action of 5 rowers under each of those performance conditions. The authors
      followed Beek's (1992) suggestion that the first task in the analysis of timing
      in skilled movement is to specify the sources of variance and invariance in each
      particular task by identifying the major temporal constraints and the key
      relative timing variables. In addition, the possibility that some simple
      mathematical relationship (e.g., Schmidt, 1985) might describe the relative
      timing between the stroke and recovery phases of the rowing action when performed
      at different speeds was investigated. Both an absolute and a relative variability
      criterion were used in assessing and comparing timing variability over 4 speeds
      of rowing and between on-water and ergometer rowing in 5 elite male subjects.
      Criteria outlined by Gentner (1987) were used in assessing relative timing
      between stroke and recovery. The results indicated that variability decreases
      dramatically as a function of increased rowing rate; however, when variability is
      expressed as a function of movement duration, those decreases appear much less
      dramatic. Overall variability of the rowing cycle was caused principally by
      variability in the recovery phase, whereas the stroke phase was relatively
      invariant under both rowing conditions. The changes in the relative timing of the
      rowing stroke across the 4 speeds studied followed a simple mathematical rule,
      best described as linear increments in the stroke proportion of the total rowing
      cycle with increases in rowing rate. Moreover, those changes were similar across
      the 2 rowing conditions. The present results are discussed in light of findings
      from other forms of propulsion, such as walking, running, and stair climbing, in
      which the movement constraints are quite different.

PMID- 20037019
TI  - Phenomenal versus process explanations of prism aftereffects.
AB  - The phenomenal hypothesis that prism aftereffects depend upon sight of the limb
      was tested in a ball-throwing task during prism exposure; the participant's (N =
      28) limb was either visible or not visible, but feedback from the moving ball was
      available during the exposure. Aftereffects were clearly demonstrated in both the
      visible- and nonvisible-limb conditions, and total aftereffect was larger for
      participants in the nonvisible-limb condition. Proprioceptive aftereffects were
      greater than visual aftereffects in the visible-limb group; however, the reverse
      was true for the nonvisible-limb group. Those results support a processing
      hypothesis in which sensory feedback, not phenomenal experience, is necessary.

PMID- 20037020
TI  - Generalized Motor Program (GMP) Learning: Effects of Reduced Frequency of
      Knowledge of Results and Practice Variability.
AB  - The effects of reduced frequency of presentation of relative-liming knowledge of
      results (KR) on constant and serial practice and whether response stability is
      associated with increased generalized motor program (GMP) learning were examined.
      Participants (N = 40) were asked to sequentially depress 4 keys (2, 4, 8, and 6)
      on the numeric pad portion of the computer keyboard by using the index fingers of
      their right hands. The frequency (50% and 100%) with which relative-timing KR was
      presented was manipulated in constant and in serial practice conditions. The
      tasks used in both the constant and the serial conditions had the same relative
      timing structure, but serial practice had 3 different absolute-timing
      requirements. The results, which indicated that reduced KR frequency enhances GMP
      learning in the serial practice condition, replicate the findings of Wulf, Lee,
      and Schmidt (1994). The reduced frequency of KR effect was not evident for the
      constant practice groups, however. More interesting was the finding that constant
      practice was significantly better than serial practice for the development and
      learning of the GMP. The data also showed that after either constant practice or
      reduced frequency of KR, response stability was enhanced in comparison with the
      stability of responses following serial practice and frequent KR. Those findings
      suggest that when response stability is improved either by reducing the frequency
      with which KR is presented or by reducing the number of task variations
      practiced, the development of the GMP is enhanced but parameter specification in
      transfer tasks tends to be degraded.

PMID- 20037021
TI  - The dynamics of gait transitions: effects of grade and load.
AB  - Diedrich and Warren (1995a) proposed that gait transitions behave like
      bifurcations between attractors, with the relative phase of the leg segments as
      an order parameter and stride frequency and stride length as control parameters.
      In the present experiments, the authors tested the prediction that manipulation
      of the attractor layout, either through the addition of load to the ankles or
      through an increase in the grade of the treadmill, induces corresponding changes
      in the walk-run transition. As predicted, the load manipulation shifted the most
      stable walk and the transition to lower stride frequencies. In contrast, the
      grade manipulation shifted the most stable walk and the transition to shorter
      stride lengths. Other features of the dynamic theory were also replicated,
      including enhanced fluctuations of phase and systematic changes in stride length
      and frequency at the transition. Overall, in these experiments a shift of the
      attractors in control parameter space yielded a corresponding shift of the
      transition.

PMID- 20037022
TI  - Age-related differences in prehension: the influence of task goals.
AB  - A single study is reported in which the influence of age and task goal on
      reaching and grasping movements were examined. Ten young and 10 elderly subjects
      reached and grasped a disk (4.5-cm diameter) and then either (a) placed it in a
      well, (b) placed It in a box, or (c) threw it in a box, all located 30 cm to the
      left of the disk. The reach-to-grasp movements were analyzed over two phases: the
      approach to capture the disk and the transporting of the disk. Differential
      effects were observed over the two phases as a function of age. Over the
      approach, the movement times of the elderly subjects were comparable with those
      of the young subjects, but their relative deceleration and hand enclosing times
      took longer. During object transport, however, the elderly subjects moved more
      slowly than the young subjects did, but there were no differences in relative
      timing. In both phases, the precision required of the task influenced the
      duration of movement and the relative timing of arm deceleration, suggesting that
      subjects accurately anticipated the demands of the task. Those results, which are
      discussed in relation to hardware and software limitations on performance,
      suggest that the age-related differences reflect changes in the use of software
      strategies over the two phases of movement.

PMID- 20037023
TI  - Near, far, or in between?-Target edges and the transport component of prehension.
AB  - It is well known that during visually guided prehension movements the peak
      velocity of the arm is scaled for object distance (e.g., Gentilucci et al., 1991;
      Jakobson & Goodale, 1991; Servos, Goodale, & Jakobson, 1992). Those movements are
      being directed not to single points in space, however, but rather to objects with
      extent. Thus, object distance must be computed relative to some particular point
      on the object. Whether that point corresponds to the location of a particular
      edge, for example, has not been clearly demonstrated. In the present study,
      subjects (N = 9) were presented with a series of oblong blocks positioned at
      different locations. Peak velocity increased with object size for reaches in
      which different-sized objects had their near edges lined up; in contrast, the
      peak velocities of reaches directed to objects of different sizes did not differ
      when the far edges of the objects were lined up. The present study, therefore,
      provided confirmation that subjects calibrate the peak velocity of their reaches
      relative to the far edge of a target object.

PMID- 20037024
TI  - (Non)Issues of infinite regress in modeling motor behavior.
AB  - In the past, infinite regress criticisms that have been raised about models of
      motor behavior have been reserved for executive-type models (e.g., Beek & Meijer,
      1988). On the basis of Godel's (1930/1986) proof that an algorithm cannot prove
      its own validity, the authors reason that executive- as well as self-organized
      type explanatory models of motor behavior have infinite regress difficulties. The
      conclusion offered in the present article is that judgments on a model's
      theoretical importance should be based not on issues of infinite regress but on
      other relevant characteristics, such as its propensity for falsification (Popper,
      1959).

PMID- 20037025
TI  - The influence of gender on spine, hip, knee, and ankle motions during a reaching
      task.
AB  - In the present study, the motions of the different postural joints involved in
      reaching tasks starting from an upright posture were examined and the influence
      of gender on the movement pattern used was determined. Specifically, motion about
      the ankle, knee, and hip joints as well as angular motion of the thoracic segment
      with respect to the sacrum (lumbar motion) were measured. Ten healthy subjects (5
      men, 5 women) reached for targets at 2 locations normalized to the subject's
      trunk length, arm length, and hip height. To reach each target, subjects had to
      bend the trunk forward. Joint motion was measured with a Selspot motion analysis
      system. The change in joint angle (measured in the sagittal plane from an upright
      standing position to the final posture adopted at target contact) was calculated
      for each joint. In addition, the ratio of the changes in joint angle of the
      lumbar spine and the hip (spine/hip ratio) was determined. Compared with female
      subjects, male subjects exhibited, on average, greater rotation about the lumbar
      spine and less rotation about the hips and knees. The spine/hip ratios for men
      and women were dramatically different. Men had, on average, a spine/hip ratio of
      1.20 and women an average of 0.20. Those data reveal that 2 vastly different
      movement patterns are employed during reaching tasks that necessitate some
      forward bending of the trunk. Men tend to flex equally about the hips and spine,
      with minimal flexion about the knees, whereas women flex primarily about the hips
      and knees, with minimal flexion about the spine. Thus, the kinematic redundancy
      is resolved differently depending on gender.

PMID- 20037026
TI  - Are older adults more dependent on visual information in regulating self-motion
      than younger adults?
AB  - Older adults look at the ground more while they are walking than younger adults
      do. In the present study, the effect of blocking that exproprioceptive visual
      information on the walking pattern of older adults was investigated. The first
      0.75 m of the floor in front of healthy young adults (n = 10, mean age = 26.0
      years) and 2 groups of older adults (n = 10, mean age 65.7 years; and n = 9, mean
      age = 75.9 years) was occluded. The dependent variables were step velocity, step
      length, and step frequency. The effect of the manipulation on those kinematic
      variables increased with age. The older adults had a significant increase in
      velocity and step length. The possible use of optic flow information from the
      ground to regulate the velocity of self-motion is discussed.

PMID- 20037027
TI  - Organization of lateral balance control in toddlers during the first year of
      independent walking.
AB  - The authors of the present study tested the hypothesis that toddlers initiate
      lateral body stabilization first at the hip level in order to better control the
      center of gravity (CG), minimize the upper body destabilization induced by the
      movement of the feet, and prevent falls. Intersegmental coordination among the
      hip, the shoulder, and the head was investigated in toddlers during their 1st
      year of independent walking. The efficiency of locomotor balance control was
      examined in the frontal plane. An automatic optical TV image processor (ELITE
      system) was used in analyzing the kinematics of foot, hip, shoulder, and head
      rotations. For the hip, the shoulder, and the head, appropriate anchoring indices
      were defined so that comparisons could be made concerning the stabilization of a
      given body segment with respect to its external space and to the adjacent
      supporting anatomical segment. Cross-correlation functions were also used for
      extracting the temporal patterns of the body segments that occurred during
      locomotion and for obtaining some information about the coupling of 2 consecutive
      segments such as the head-shoulder and the shoulder-hip. First, hip stabilization
      in space appeared from the 1st week of independent walking and clearly preceded
      those of the shoulder and the head, suggesting an ascending progression, with
      age, in the ability of new walkers to control lateral balance during locomotion.
      Second, the hip movements occurred before the shoulder movements and the shoulder
      movements before the head movements, indicating that locomotor balance control is
      organized temporally in an ascending fashion, from the hip to the head. Third,
      the high values of the correlation coefficients, mainly between the head and the
      shoulder, were consistent with a global en bloc operation of the head-trunk unit.

PMID- 20037028
TI  - Blocking in rapid finger tapping: the role of variability in proximodistal
      coordination.
AB  - In rapid finger tapping, occasional intertap intervals of about twice the normal
      length or even longer, called blockings, can be observed. Skilled rapid tapping
      requires that flexor and extensor activity be timed so that they coincide with
      certain phases of the finger movement. In the present study, the hypothesis
      examined was that blockings are associated with a deviation from the proper
      timing relations between the more proximal signals (electromyographic [EMG]
      bursts) and the more distal signal (position-time curve of the finger).
      Participants (N = 8) performed up-and-down tapping. Blockings were compared with
      the preceding normal tapping cycles; a temporal forward shift of the flexor burst
      in the time interval between two kinematic landmarks-the lifting of the finger
      and the reversal of the movement-was found consistently in the blockings The
      phase shift of the flexor burst relative to the kinematic landmarks did not
      develop gradually in the course of the tapping cycles that preceded the blocking
      but was an abrupt deviation, which suggests that blockings occur with an
      increased likelihood as the extremes of the normal variability of the phase
      relation are approached.

PMID- 20037029
TI  - Practice does not diminish the role of visual information in on-line control of a
      precision walking task: support for the specificity of practice hypothesis.
AB  - It has been proposed that motor learning is specific to the sources of afferent
      information available during practice (Proteau, 1992). That hypothesis has
      obtained support from studies of aiming but not from studies of gross motor
      skills. The many procedural differences between the two sets of studies might
      have caused the conflicting results. In the present investigation of a precision
      walking task, the validity of the specificity of practice hypothesis was tested.
      Thirty-two participants were asked to walk for 20 m on a 2.5-cm-wide line.
      Subjects practiced the task for either 20 or 100 trials under normal visual
      conditions or while blindfolded. Following acquisition, all subjects performed
      the task for 20 additional trials while blindfolded and without knowledge of
      results. Practice improved the performance of blindfolded participants.
      Withdrawing vision in transfer resulted in a large and significant increase in
      error, however, a finding that supports the specificity of practice hypothesis.

PMID- 20037030
TI  - Contextual interference in learning new patterns of bimanual coordination.
AB  - Two experiments are reported in which the question of whether or not contextual
      interference effects are found in motor tasks that require the acquisition of new
      coordination patterns was examined. Participants (N = 18, Experiment 1; N = 12,
      Experiment 2) practiced 3 novel bimanual patterns (45 degrees , 90 degrees , and
      135 degrees relative phase) in either a random or a blocked order. No
      statistically significant acquisition or retention differences between groups
      were found when all 3 patterns were practiced on each of 2 days (Experiment 1).
      When the blocked group practiced 1 pattern on each of 3 acquisition days
      (Experiment 2), however, typical contextual interference effects were found: The
      blocked group performed better than the random group in practice, but the random
      group performed better than the blocked group in a delayed (by I week) retention
      test. The experiments revealed that contextual interference effects can arise in
      motor tasks that require the acquisition of new coordination patterns and are not
      limited to tasks involving novel scaling of a previously existing pattern.

PMID- 20037031
TI  - Interaction of tremor and magnification in a motor performance task with visual
      feedback.
AB  - In this study, the interaction between increased gain in the visual feedback loop
      and motor control of the periphery was investigated. Participants (N = 15) were
      asked to maintain a constant finger position while they used magnified visual
      feedback. The measure of the accuracy of each trial was the standard deviation
      (trial error) of the finger position. Trials performed under magnification had
      lower trial errors than trials without magnification. The change in trial error
      between trials with and without magnification proved greater than the difference
      between trials at any 2 magnifications. In contrast, the differences between
      individual subjects were often greater than the differences between performances
      at individual magnifications. At higher magnifications, performance seemed to be
      limited by the tremor; the ratio of trial error to tremor intensity was constant.
      When applied to microsurgery, the present results accord with those found in
      earlier research, including investigations that have found that the level of
      magnification used in microsurgery is not the most significant factor in
      achieving good results and that tremor is the limiting factor in microsurgical
      tasks.

PMID- 20037032
TI  - Instructions for motor learning: differential effects of internal versus external
      focus of attention.
AB  - The effects of different types of instructions on complex motor skill learning
      were examined. The instructions were related either to the participant's own body
      movements (internal focus) or to the effects of those movements on the apparatus
      (external focus). The hypothesis tested was that external-focus instructions
      would be more beneficial for learning than internal-focus instructions. In
      Experiment 1, the participants (N = 33) performed slalom-type movements on a ski
      simulator. The instructions referred to the way in which force should be exerted
      on the platform that the participant was standing on. The instructions given 1
      group of participants referred to the performers' feet (internal focus), whereas
      the instructions given another group referred to the wheels of the platform,
      which were located directly under the feet (external focus). The control group
      was given no focus instructions. All participants practiced the task on 2
      consecutive days and performed a retention test on Day 3. Compared with the
      effects of internal-focus instructions and no instructions, the external-focus
      instructions enhanced learning. Internal-focus instruction was not more effective
      than no instructions. In Experiment 2, an attempt was made to replicate the
      differential effects of external-versus internal-focus instructions with a
      different task (balancing on a stabilometer). Consistent with Experiment 1,
      instructing learners (N = 16) to focus on 2 markers on the platform of the
      stabilometer (external focus) led to more effective learning than instructing
      them to focus on their feet (internal focus), as measured by a retention test
      after 2 days of practice. Practical and theoretical implications of those results
      are discussed.

PMID- 20037033
TI  - Frequent feedback enhances complex motor skill learning.
AB  - Feedback frequency effects on the learning of a complex motor skill, the
      production of slalom-type movements on a ski-simulator, were examined. In
      Experiment 1, a movement feature that characterizes expert performance was
      identified. Participants (N = 8) practiced the task for 6 days. Significant
      changes across practice were found for movement amplitude and relative force
      onset. Relative force onset is considered a measure of movement efficiency;
      relatively late force onsets characterize expert performance. In Experiment 2,
      different groups of participants (N = 27) were given concurrent feedback about
      force onset on either 100% or 50% of the practice trials; a control group was
      given no feedback. The following hypothesis was tested: Contrary to previous
      findings concerning relatively simple tasks, for the learning of a complex task
      such as the one used here, a high relative feedback frequency (100%) is more
      beneficial for learning than a reduced feedback frequency (50%). Participants
      practiced the task on 2 consecutive days and performed a retention test without
      feedback on Day 3. The 100% feedback group demonstrated later relative force
      onsets than the control group in retention; the 50% feedback group showed
      intermediate performance. The results provide support for the notion that high
      feedback frequencies are beneficial for the learning of complex motor skills, at
      least until a certain level of expertise is achieved. That finding suggests that
      there may be an interaction between task difficulty and feedback frequency
      similar to the interaction found in the summary-KR literature.

PMID- 20037034
TI  - Midreach correction in 7-month-olds.
AB  - In recent work, it has been suggested that infant reaching is composed of a
      sequence of perception-action cycles in which the positions of the hand and the
      target are assessed and actions are generated that bring the hand to the target.
      In the present work, the author examined the ability of 7-month-old infants (N =
      12) to correct reaches in midflight when a target location was shifted. The
      results showed that on the majority of shift trials, the infants corrected hand
      direction in midreach and that the latency of correction was 200-400 ms. Although
      the present results are limited to the case of the infant's response to a target
      shift, they are consistent with the hypothesis that infants monitor the positions
      of the hand and the target during the reach and are able to adjust for any errors
      of movement.

PMID- 20037035
TI  - Can people tap concurrent bimanual rhythms independently?
AB  - If people could tap 2 rhythms independently, 1 rhythm with each hand, training
      people to tap the rhythms separately should enable them to tap the rhythms
      concurrently. However, nonmusician participants in the present experiments were
      unable to produce accurate intervals when lapping bimanually after they had
      mastered the rhythms individually. That finding implies that tapping concurrent
      rhythms requires an integrated sensory-motor representation incorporating the
      actions of both hands into a single pattern. Although training the rhythms
      separately cannot specify an integrated code, such specification is possible with
      bimanual training. Bimanual training quickly led to accurate tapping, but most
      participants then did not tap correctly either of the separate rhythms that had
      been mastered in the context of concurrent tapping. That finding suggests that
      the integrated representation does not code either rhythm independently.

PMID- 20037036
TI  - Interlimb coordination as a function of isometric force output.
AB  - In the 2 experiments reported here, the influence of level of force output on
      interlimb coordination in an isometric force tusk was examined. Healthy adults (N
      = 8) were required to match a continuous total level of isometric force produced
      by the output of the two index fingers over a range of force levels (1 % to 80%
      ot maximum). The results showed that (a) coordination between fingers increased
      as force level increased; (b) coordination between fingers was less than that of
      the force output of each finger to the total force, but that difference in
      relative coordination decreased as target force levels increased; and (c) the
      regularity of the force output of each finger considered separately was greater
      than that of the total force. Overall, force level was found to have a small but
      reliable effect on interlimb coordination within a compensatory action between
      fingers that reduces task error.

PMID- 20037037
TI  - Monocular and binocular vision in one-hand ball catching: interocular
      integration.
AB  - In 2 experiments, binocular and monocular vision were compared and interocular
      integration in 1-hand ball catching was examined. Participants (N = 10 in each
      experiment) were required to catch tennis balls projected over a distance of 15
      m. Participants wore liquid-crystal visual occlusion goggles so that the duration
      and frequency of visual samples provided to their eyes over ball flight could be
      manipulated. An examination of catching performance indicated that binocular
      vision contributed to both the spatial and temporal aspects of the catching task.
      Experienced catchers are able to integrate information from the 2 eyes over
      intervals as long as 80-100 ms. When provided with only intermittent monocular
      samples of ball flight, catching performance deteriorated rapidly as the interval
      between consecutive samples was increased. Results are discussed both in terms of
      the sources of visual information useful for the interception of objects and the
      temporal differences for interocular integration between the perception of form
      and visual-motor control.

PMID- 20037038
TI  - Perception of postural limits during reaching.
AB  - The relationship between perceived and actual postural limits in reaching by
      healthy young and middle-aged participants was assessed. Subjects (N = 51) first
      estimated their expected performance and then executed maximum reaches along a
      tape measure mounted at shoulder height. Measures of standing and bending reaches
      were obtained. Subjects estimated their reach limits reasonably accurately but
      significantly underestimated bending reach and overestimated standing reach. That
      finding suggests that individuals scale perceived abilities with perceived risk
      in attempting a given action. The accuracy of a participant's perceived bending
      reach was unrelated to his or her height, weight, age, and gender, and was only
      weakly correlated with actual reach excursion (bending - standing reach). The
      accuracy was strongly correlated with the accuracy of subjects' perceived
      standing reach; individuals who underestimated standing reach underestimated
      bending reach much more. That result and the observed lack of correlation between
      the magnitudes of estimated bending reach and estimated standing reach suggest a
      serial strategy of estimating bending reach by considering and summing perceived
      arm's length and perceived reach excursion.

PMID- 20037039
TI  - A comparison of two-dimensional and one-dimensional tracking performance in
      normal subjects.
AB  - A study comparing the function of the normal sensory-motor system in 1
      dimensional (1D) and 2-dimensional (2D) environments was undertaken. Performances
      on a PC-based 2D eye-aim random pursuit tracking task and a 1D version of that
      task were compared. Sixteen normal subjects (8 men and 8 women) participated in
      the study. The subjects" tracking performance was found to deteriorate when they
      changed from the 1D to the 2D task. The subjects' performance on a 2D task with
      the same average velocity and displacement as the 1D task was degraded, primarily
      because of the increase in the dimensionality of the task. An older age group had
      a marginally greater degradation in performance on going from a 1D to a 2D task
      than a younger age group No significant differences in performance or
      degradations in performance were found between the men and women.

PMID- 20037040
TI  - Physical-guidance benefits in learning a complex motor skill.
AB  - The effects of physical guidance on learning to perform slalom-type movements on
      a ski-simulator were examined in 22 participants (18 in Experiment 1, 4 in
      Experiment 2). In Experiment 1, 1 group of participants practiced the task with
      ski-poles whereas another group practiced without poles. Retention tests without
      poles were performed at the end of each of the 2 practice days and 1 day later.
      Although the use of poles produced more effective performance in terms of
      movement amplitude during practice, both conditions led to similar amplitudes in
      immediate and delayed retention. With regard to the efficiency of the movement
      pattern, the pole group demonstrated a more efficient coordination pattern than
      the no-pole group did, not only during practice but also in immediate (Day 2) and
      delayed retention. In Experiment 2, how the poles functioned to enhance the
      learning of a more efficient movement pattern was examined more closely. The
      results suggest that physical guidance can have beneficial effects not only on
      performance during practice but also-under certain conditions-on the learning of
      motor skills.

PMID- 20037041
TI  - Index for volume 30.

PMID- 20037042
TI  - 1998 ad hoc reviewers for the journal of motor behavior.

PMID- 20037077
TI  - Editorial policy and instructions for authors.

PMID- 20037043
TI  - Can the transitions to and from running and the metabolic cost of running be
      determined from the kinetic energy of running?
AB  - An experiment was conducted in which volume of used oxygen per stride time and
      the total segmental changes in kinetic energy generated per stride time, DeltaEk
      s-1, of 11 participants were determined on Day 1 for 7 treadmill running speeds.
      Gait transition speeds were determined on Day 2. Running metabolism and
      transition speed were predicted from the Day 1 mechanics of running expressed in
      Speed x DeltaEk s-1 coordinates. Predictions followed from the relation between 2
      generalized quality ratios Qmetab, and Qmech, with numerator DeltaEk s-1. In
      Qmetab, the denominator was the volume of used oxygen per stride time; in Qmech,
      the denominator was the absolute regression constant from the linear dependency
      of DeltaEk s-1 on speed.

PMID- 20037078
TI  - Instruction-dependent muscle activation patterns within a two-joint synergy:
      separating mechanics from neurophysiology.
AB  - The following issue was addressed in the present study. Can instruction modify
      the involvement of different muscles when mechanical conditions and
      characteristics of a motor task remain unchanged? Subjects (N = 9) produced force
      by pressing their right hands against a fixed pad and were asked, in different
      trials, to predominantly use muscles that control either their elbows or their
      wrists. Force characteristics remained the same. In some trials, the setup was
      unexpectedly released so that a flexion movement occurred. Instruction changes
      induced changes in the muscle activation patterns and in preprogrammed reactions
      seen in unexpectedly released trials. The authors conclude that there may be
      different neurophysiological solutions to a specific mechanical task and that
      patterns of muscle activation may reflect features of both the explicit motor
      task and the subject's intention that may have no obvious mechanical correlate.

PMID- 20037079
TI  - Breaking the reflectional symmetry of interlimb coordination dynamics.
AB  - Interlimb rhythmic coordination is reflectionally symmetric when the left and
      right limb segments are identical in uncoupled frequencies and spatial
      orientation. In the present studies (4 experiments, with a total of 31
      participants), when reflectional symmetry was broken through differences in
      timing (frequency), the resulting stable states were related by reflection and
      were identical for paired identically oriented limb segments behaving either as
      inverted or as ordinary pendulums. When reflectional symmetry was broken both
      temporally and spatially (coordinating inverted and ordinary pendular motions),
      the resulting stable states were different from those produced by identically
      oriented pendulums but nevertheless were related by reflection. In the
      Discussion, the authors focus on (a) symmetry breaking as leading to one of a
      number of symmetrically related states and (b) extending coordination dynamics
      with reflectional symmetry so that temporal and spatial asymmetries can both be
      accommodated.

PMID- 20037080
TI  - Kinematic coordination of reach and balance.
AB  - In the present article, the authors review inverse kinematic research across a
      number of fields to highlight the similarities among modeling approaches to the
      problems of reaching and maintenance of posture. Two particular techniques are
      described: the Berkinblit algorithm, used to model the leg-wiping reflexes of the
      frog, and the parallel control scheme of Hinton, in which simple stick-man
      simulations maintain a balanced posture while reaching. Those 2 algorithms are
      shown to be equivalent to one another and are described in terms of transpose
      jacobian control. A controller based on those methods is compared with one based
      on resolved motion rate control or pseudoinverse control, commonly used in
      robotics applications. Both controllers are applied to the problem of
      coordinating reaching and balancing behavior in a simulated 3-dimensional
      anthropomorphic robot. It is demonstrated that both of those techniques can
      produce postures that are surprisingly natural.

PMID- 20037081
TI  - Adaptation in visuomanual tracking depends on intact proprioception.
AB  - The role of arm proprioception in motor learning was investigated in experiments
      in which, by moving the arm, subjects followed the motion of a target displayed
      on a monitor screen. Adaptive capabilities were tested in visuomanual tracking
      tasks following alterations in the relationship between the observer's actual arm
      movement and visual feedback of the arm movement given by a cursor motion on the
      screen. Tracking performance and adaptive changes, measured in terms of
      spatiotemporal error, tracking trajectory curvature, and spatial gain, were
      compared in 7 control subjects (CSs) and in 1 deafferented subject (DS). CSs
      adapted appropriately to altered visuomanual relationships; those changes were
      present in trials immediately after restoration of normal scaling. In contrast,
      although the DS modified his tracking strategy from trial to trial according to
      the altered conditions, he did not show plastic changes in internal visuomanual
      scaling. Like the results of prismatic adaptation experiments, the present
      results suggest that arm proprioception contributes to the plastic changes that
      follow alterations in the scaling of visuomanual gain.

PMID- 20037082
TI  - Temporal and spatial coupling of point of gaze and hand movements in aiming.
AB  - Temporal and spatial coordination of both point of gaze (PG) and hand kinematics
      in a speeded aiming task toward an eccentrically positioned visual target were
      examined with the Optotrak 3D movement analysis system in tandem with the ASL
      head-mounted eye tracker. Subjects (N = 10) moved eyes, head, hand, and trunk
      freely. On the majority of trials, the PG pattern was a large initial saccade
      that undershot the target slightly, then 1 or more smaller corrective saccades to
      reach the target. The hand exhibited a similar pattern of first undershooting the
      target and then making small corrective movements. Previously (W. F. Helsen, J.
      L. Starkes, & M. J. Buekers, 1997), the ratio of PG and total hand response time
      (50%) was found to be an invariant feature of the movement. In line with those
      results, a striking temporal coupling was found between completion of the primary
      eye saccade and time to peak acceleration for the limb. Spatially, peak hand
      velocity coincided with completion of 50% of total movement distance. Those
      findings support a 2-component model of limb control.

PMID- 20037083
TI  - The effect of posture on early reaching movements.
AB  - Infants of about 5 months of age who have just mastered the ability to reach
      succeed more frequently in contacting an object when they are seated upright than
      when they are supine or reclined. That effect of posture disappears in the
      subsequent months. Whether that effect can be attributed either to insufficient
      muscular strength or to insufficient control over the mechanically unstable arm
      was the subject of the present investigation. Kinematics and electromyography
      (EMG) of reaching movements of 8 sitting and supine infants at 12, 16, and 20
      weeks of age were recorded. Maximum levels of shoulder torque as well as
      kinematic stability measures were similar in both postures. Coactivation levels
      and the frequency of on-off switching of muscles turned out to be higher in the
      sitting than in the supine posture. The authors suggest that the difference in
      reaching behavior resulted from the degree of error in the feedforward control
      signal that was allowed by the different postures rather than either insufficient
      muscular strength or insufficient control over the mechanically unstable arm.

PMID- 20037084
TI  - Finding final postures.
AB  - In this study, a model of movement planning (Rosenbaum, Engelbrecht, Bushe, &
      Loukopoulos, 1993a, 1993b; Rosenbaum, Loukopoulos, Meulenbroek, Vaughan, &
      Engelbrecln, 1995), in which movements are generated on the basis of the efficacy
      of different possible goal postures, was tested. The model predicts which limb
      segments will be used and how the segments will be combined in reaching. The
      model's predictions were compared with observations from a study in which seated
      participants reached for targets in a sagittal plane, using the hip, shoulder,
      and elbow. Estimates of 4 free parameters-an expense factor for each of the 2
      contributing joints, and a 4th parameter that specified the relative weight of
      spatial accuracy versus effort minimization, were used for fitting the model to
      the observed joint angles. The model accounted for 96% of the variance of the
      observed joint angles and did a better job accounting for the data than several
      alternative models. A key new finding was that balance constraints play a more
      important role in determining joint contributions than was previously recognized.

PMID- 20037085
TI  - Comment on conduction velocity in muscle and cutaneous nerve afferents in humans.
AB  - The conduction velocities in muscle and cutaneous nerve afferents of cats are
      considerably faster than those of comparable axons in humans. Texts on human
      physiology and neurophysiology tend to show conduction velocities and diameters
      derived from studies on cats, without stating that those values are not
      applicable to humans. Apart from showing the need for a clearer attribution of
      the sources of data, the differences raise interesting questions about the
      functional significance of the relatively small diameters and low conduction
      velocities of muscle and cutaneous nerve afferents in humans.

PMID- 20037086
TI  - Note from the editors.

PMID- 20037087
TI  - 1999 annual index.

PMID- 20037095
TI  - Endoscopic radial artery harvesting for coronary artery bypass grafting: the
      initial clinical experience and results of the first 50 patients.
AB  - BACKGROUND: The radial artery (RA) is a commonly used arterial conduit in
      coronary artery bypass grafting (CABG). Traditional open-vessel harvest often
      leads to postoperative wound complications and cosmetic problems. Endoscopic RA
      harvesting (ERAH) has been widely used to prevent these problems. The purpose of
      this study was to assess these problems and graft patency in the first 50
      patients who underwent ERAH. METHODS: Between February 2006 and October 2007, 50
      patients underwent ERAH with the VasoView system (Boston Scientific). These
      patients were compared with 50 patients who underwent the traditional open
      technique. RESULTS: The mean age was 62.8 years in both groups. All RAs were
      successfully harvested. No conversion was made from ERAH to the traditional open
      technique. The mean harvesting time (forearm ischemic time) was 27.4 + or - 6.5
      minutes, and the mean length of the RA in the ERAH group was 18.5 cm. Neither
      wound complications, such as wound infection and skin necrosis, nor severe
      neurologic complications were recorded. The patency rate was 95.9% (95/99) in the
      ERAH group and 94% (94/100) in the open group. CONCLUSION: ERAH can be performed
      safely, and the early results are satisfactory. Endoscopic vessel harvesting is
      therefore recommended as the technique of choice for RA harvesting.

PMID- 20037096
TI  - Myocardial protective effect of urethane on isolated rat hearts in prolonged
      hypothermic preservation.
AB  - BACKGROUND: One of the most important factors restricting heart transplantation
      is the limited myocardial ischemia time. This study investigated the effects of
      urethane on the hypothermic preservation of donor rat hearts. MATERIALS AND
      METHODS: Hearts isolated from rats were divided into 2 groups (n = 8), a control
      group with histidine-tryptophan-ketoglutarate (HTK) solution alone and an
      experimental group with HTK solution plus 30 mM urethane. Hearts were mounted on
      a Langendorff apparatus to estimate the baseline cardiac function; the hearts
      were then arrested and stored in one of the 2 solutions for 6 hours and 18 hours
      at 4 degrees C. After preservation, the hearts were reperfused, and cardiac
      function was evaluated. Lactate dehydrogenase (LDH) release, adenosine
      triphosphate (ATP) content, cardiomyocyte apoptosis, and myocardial
      ultrastructure were examined. RESULTS: Compared with the control group, the
      experimental group showed a significantly higher recovery of cardiac function for
      both 6 hours and 18 hours of preservation and demonstrated a lower rate of
      cardiomyocyte apoptosis (8.5% + or - 1.2% versus 12.2% + or - 1.8% for 6 hours;
      14.1% + or - 2.1% versus 31.4% + or - 2.7% for 18 hours). ATP content was
      significantly higher in the experimental group than in the control group after 18
      hours of preservation (229.4 + or - 29.7 microg/g versus 153.2 + or - 21.1
      microg/g). The experimental group also showed lower levels of LDH release after
      18 hours of preservation. Electron microscopy studies demonstrated better
      cardiomyocyte structure in the experimental group for both 6 hours and 18 hours
      of preservation. CONCLUSIONS: Use of urethane improved cardiac functional
      recovery and led to significant protective effects on rat hearts placed in a
      hypothermic preservation solution for a prolonged period.

PMID- 20037097
TI  - Transaortic repair of the mitral valve in patients undergoing aortic valve
      replacement.
AB  - OBJECTIVE: We retrospectively evaluated the results of edge-to-edge (Alfieri)
      repair of the mitral valve via a transaortic approach in patients undergoing
      aortic valve replacement (AVR) and who had significant mitral regurgitation (MR).
      METHODS: From July 2000 to June 2006, 13 patients underwent edge-to-edge repair
      of the mitral valve via a transaortic approach with concomitant AVR. Patients
      were considered eligible for the transaortic Alfieri repair if the preoperative
      transesophageal echocardiogram indicated that the MR jet originated in the middle
      portion (A2/P2 segments) of the mitral valve. A postoperative transesophageal
      echocardiogram and follow-up transthoracic echocardiograms were obtained.
      RESULTS: There was no operative mortality. There was a significant improvement in
      the median MR grade from 3 (interquartile range [IQR], 2-4) preoperatively to 1
      (IQR, 1-1) postoperatively (P < .0001). The ejection fraction (EF) remained
      stable, with mean preoperative and postoperative EFs of 44.2% + or - 14.9% and
      46.27% + or - 11.6%, respectively (P = .4). No mitral stenosis was noted in any
      of the patients following edge-to-edge repair. Follow-up transthoracic
      echocardiograms obtained at a mean of 12.5 months postoperatively (range, 1-34
      months) showed a median MR grade of 1 (IQR, 1-2) with no worsening compared with
      immediately postoperatively (P = .4). CONCLUSION: Transaortic edge-to-edge repair
      of the mitral valve in patients undergoing AVR is feasible. The postoperative
      improvement in MR was maintained at the midterm follow-up.

PMID- 20037098
TI  - High-risk left main coronary artery bypass surgery supported by the Impella
      Recover LP 2.5 assist device: an alternative insertion technique.
AB  - Patients with high-risk coronary lesions such as left main stenosis and a
      severely depressed left ventricular ejection fraction are at risk of death and
      morbidity-related complications during coronary artery bypass surgery. Several
      alternative methods have been developed for managing this problem, but it is
      still challenging, even for highly experienced and well-equipped cardiac surgery
      centers. We report the case of a successful coronary artery bypass surgery
      supported by the Impella Recover LP 2.5 assist device and using an alternative
      insertion technique for the ascending aorta in a patient with high-risk coronary
      lesions, such as left main disease.

PMID- 20037100
TI  - Female risk using OPCAB, pi-circuit, and aorta no-touch coronary
      revascularization.
AB  - BACKGROUND: In this study, we evaluated female sex as a risk factor in the off
      pump coronary artery bypass (OPCAB), aorta no-touch technique. MATERIALS AND
      METHODS: From February 2001 to November 2005, 1359 patients in our institution
      underwent isolated coronary revascularization with the pi-circuit technique,
      which consists of (1) beating heart surgery, (2) OPCAB, (3) no touching of the
      aorta, (4) use of composite grafts, and (5) arterial revascularization. There
      were 1159 men (group A) and 200 women (group B). Both groups were compared with
      respect to preoperative risk factors, intraoperative parameters, and
      postoperative morbidity and mortality. Follow-up lasted from 4 to 60 months. Data
      were analyzed with the chi(2) test, the Fisher exact test, the Kaplan-Meier
      method, and the Cox model of regression analysis. RESULTS: Female patients were
      older (P < .0005) and had higher prevalences of obesity (P < .0005), arterial
      hypertension (P < .0005), and diabetes (P < .0005). Emergency operations were
      also more frequent in this group (P < .027). There was no difference between the
      groups in the preoperative use of an intra-aortic balloon pump (IABP). The 2
      groups were not significantly different with respect to 30-day mortality (1.1%
      versus 4%) or 7-day mortality (0.3% versus 0%). The 2 groups had comparable rates
      of IABP use postoperatively. Cognitive disturbances and strokes were rarely
      encountered (0.6% in men and 0.2% in women). In the early postoperative phase,
      women had more pulmonary complications (P < .014), and survival seemed to favor
      the male group during the follow-up period (P < .001). Further analysis with the
      Cox regression model with exclusion of confounding preoperative morbidity factors
      (more prevalent in group B) showed that the 2 groups had similar survival rates.
      As a group, women were 1.06 times more likely to die from a cardiac cause than
      men (P < .897). CONCLUSIONS: The use of the pi-circuit, aorta no-touch technique
      is equally effective and safe for both sexes. Women are more prone to pulmonary
      complications in the early postoperative phase. The apparent difference in
      survival favoring men can be attributed to the higher prevalence of preoperative
      risk factors in women. In general, we consider the off-pump, aorta no-touch
      technique an effective method for lowering morbidity and mortality in the
      relatively high-risk female patient group.

PMID- 20037101
TI  - Aorta no-touch off-pump coronary artery revascularization in octogenarians: 5
      years' experience.
AB  - BACKGROUND: Approximately 18% of octogenarians have ischemic heart disease.
      Increasingly, they are being referred for coronary artery revascularization by
      surgical and/or percutaneous procedures. These strategies have been questioned,
      however, because of reports of poor outcomes in the elderly. In this study, we
      aimed to determine the impact of age on morbidity and mortality in patients
      undergoing off-pump coronary artery bypass (OPCAB) with the pi-circuit procedure
      during 5 years of follow-up. MATERIALS AND METHODS: From February 2001 to
      November 2005, 1359 patients underwent isolated coronary revascularization with
      the pi-circuit technique, which consists of (1) beating heart surgery, (2) OPCAB,
      (3) no touching of the aorta, (4) use of composite grafts, and (5) arterial
      revascularization. Sixty-two patients were > or = 80 years of age (group A), and
      1297 were <80 years old (group B). Both groups were compared with respect to
      preoperative risk factors, intraoperative parameters, and postoperative morbidity
      and mortality. Follow-up lasted from 4 to 60 months. Data were analyzed with the
      chi(2) test, the Fisher exact test, the Kaplan-Meier method, and the Cox model of
      regression analysis. RESULTS: Females predominated among the octogenarians (P <
      .0005). Octogenarians more frequently underwent emergent operations (P < .031)
      and had worse ejection fractions (P < .026). Obesity was also less prevalent
      among these patients (P < .007). There were no differences between the groups in
      the preoperative and postoperative use of an intraaortic balloon pump.
      Octogenarians had lower cholesterol levels (P < .0005) and had fewer distal
      anastomoses (2.24 + or - 0.0.76 versus 2.77 + or - 0.92, P < .0005). The 2 groups
      were not significantly different with respect to 30-day mortality (3.2% versus
      1.5%) and 7-day mortality (1.6% versus 0.2%). Differences were noted in the
      incidences of pulmonary complications (12.9% versus 5.6%, P < .027), atrial
      fibrillation (41.9% versus 19%, P < .0005), and cognitive disturbances (6.5%
      versus 0.3%, P < .0005). During follow-up, survival seemed to favor the younger
      group (P < .001). Nevertheless, further analysis of the data with the Cox
      regression model to exclude confounding risk factors, revealed the survival rates
      of the 2 groups to be similar. CONCLUSIONS: Use of the pi-circuit technique is
      very effective for octogenarians. Although these older patients have a higher
      incidence of early postoperative morbidity, overall survival is not affected.

PMID- 20037102
TI  - Long-term results after reconstructive surgery for aneurysms of the left
      ventricle.
AB  - BACKGROUND: Aneurysms of the left ventricle (LV) present a serious consequence of
      myocardial infarction, causing mechanical, thromboembolic, and arythmogenic
      complications. We present our experience in LV remodeling and long-term follow-up
      results. METHODS: From May 1998 to February 2009, 85 patients with postinfarction
      LV aneurysm underwent reconstructive procedures. Mean age was 58.7 + or - 8.9
      years (range 36-79 years). Average LV ejection fraction was 39.8% + or - 13.1%
      (range 20%-70%). Mean EuroScore was 6.0 + or - 2.9 (range 3-19) and predictive
      mortality was 8.2% + or - 11.9% (range 1.6%-85.6%). The majority of patients were
      in New York Heart Association functional class II (44%) preoperatively and 32% of
      patients were in New York Heart Association class III or IV. LV reconstruction
      was performed by using the endoventricular patch technique in 56 patients (66%).
      In 29 patients (34%) reconstruction was done by linear closure. In 79 patients
      (93%) concomitant myocardial revascularization was performed. Mitral valve
      procedures were performed in 11 patients (13%), (repair in 10 patients and
      replacement in 1). RESULTS: Perioperative mortality was 3.5% (3 patients). Long
      term follow-up was completed by means of phone interview with an average duration
      of 31.6 months (range 3-120 months). There were 9 late deaths (11%) during follow
      up. Actuarial survival rates at 1, 5, and 10 years were 91%, 77%, and 68%,
      respectively. Fifty-nine patients (72%) were in New York Heart Association
      functional class I and II postoperatively. CONCLUSION: LV remodeling is a safe
      surgical procedure with low perioperative morbidity and mortality and excellent
      long-term survival, even in patients with severely reduced systolic function.

PMID- 20037103
TI  - Reduction of microembolic signals with a single-clamp strategy in coronary artery
      bypass surgery: a pilot study.
AB  - BACKGROUND: Neurologic deficits are perhaps the most feared form of adverse
      outcome following cardiac surgery. Aortic trauma generates emboli and hence
      harbors the potential for neurocognitive injury. The single aortic clamp strategy
      of coronary artery bypass grafting (CABG) aims at reducing aortic manipulation.
      We hypothesized that this strategy will lead to a reduction in the number
      microembolic signals (MES) evaluated by transcranial Doppler (TCD), a surrogate
      measure of cerebral embolism. METHODS: This pilot study was based on a
      prospective analysis of 22 patients in whom CABG was performed either with a
      single aortic clamp (SC group) or with a conventional multiple aortic side-clamp
      technique (MC group). The 2 groups did not differ with respect to mean age (60 +
      or - 6 years versus 65 + or - 8 years, not statistically significant [NS]) or
      EuroSCORE (2.1 + or - 1.5 versus 2.9 + or - 2, P = NS). The neurocognitive
      evaluation was based on the mini-mental state examination (MMSE). The
      preoperative MMSE values for the SC and MC groups were similar (29.5 + or - 0.5
      and 29.2 + or - 1, respectively; P = NS). RESULTS: The total number of solid
      particle embolization signals secondary to aortic manipulation was lower in the
      SC group than in the MC group (72 + or - 28 versus 127 + or - 69, P = .02).
      Neurocognitive performance was moderately reduced in both groups compared with
      preoperative values. This reduction was more pronounced in the MC group than in
      the SC group (22.2 + or - 4.1 versus 25.3 + or - 1.6, P = .02). One patient in
      the MC group had a reversible ischemic neurologic deficit (P = NS). There were no
      deaths or perioperative myocardial infarctions in either group. CONCLUSIONS: The
      single-clamp CABG strategy led to a reduction in MES, indicating a less
      pronounced embolic burden than with the conventional side-clamp CABG strategy.
      This strategy translated into a better performance in postoperative
      neurocognitive testing in the SC group of patients.

PMID- 20037104
TI  - Detecting volume responders prior to implantation of a cardiac resynchronization
      therapy device via minithoracotomy: the septal flash as a predictor of immediate
      left ventricular reverse remodeling.
AB  - BACKGROUND: Although cardiac resynchronization therapy (CRT) is well established
      as an adjunctive heart failure treatment, a 30% rate of nonresponders poses a
      challenge to improve the detection of potential responders prior to device
      implantation. A previously proposed mechanism-based approach to patient selection
      suggests in part that the septal flash is a sign of intraventricular
      dyssynchrony, which is predictive of CRT responsiveness. METHODS: In this pilot
      study, data from 5 consecutive patients (2 women and 3 men; mean + or - SD age,
      62 + or - 9 years) referred for CRT device implantation via a minithoracotomy
      were analyzed. Intraoperative transthoracic and/or transesophageal
      echocardiography data, as well as Doppler myocardial imaging data, were acquired
      before and after CRT device activation. The septal flash was defined as an early
      ventricular inward and outward septal motion within the isovolumic contraction
      period and was imaged with grayscale imaging or tissue Doppler color M-mode.
      Reverse remodeling was defined as a reduction in the left ventricular end
      systolic volume (LVESV) of > or =10%. The right atrial and right ventricular
      leads were placed transvenously, and the LV screw-in lead was positioned
      epicardially on the lateral wall. RESULTS: The septal flash was detected
      preoperatively in all patients and resolved immediately after the onset of
      biventricular pacing. Immediately following pacemaker activation, we measured a
      significant reduction in the LVESV (248 + or - 99 mL versus 190 + or - 100 mL, P
      = .01) and an increase in the ejection fraction (19% + or - 5% versus 28% + or -
      5%, P = .01) in all patients. Likewise, a significant increase in the
      postactivation dP/dt (rate of LV pressure change) measured noninvasively from the
      mitral regurgitation trace was noted in all patients (298.6 + or - 58.0 mm Hg/s
      versus 601.7 + or - 111.2 mm Hg/s, P = .001). CONCLUSION: The preoperative
      presence of the septal flash is a valid predictor of the response to CRT.
      Immediately after CRT device activation, the septal flash disappears, and LV
      reverse remodeling and an increase in contractility are observed.

PMID- 20037105
TI  - Heparin-induced thrombosis without thrombocytopenia causing fulminant pulmonary
      embolism after off-pump coronary artery bypass grafting.
AB  - Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication of
      heparin administration. A potentially life-threatening complication, HIT is
      difficult to diagnose in patients in the intensive care unit after cardiac
      surgery because there can be multiple reasons for thrombocytopenia. Moreover,
      immune-mediated platelet consumption may be masked by reactive thrombocytosis,
      which is common in the typical postoperative course after cardiac surgery. We
      report the case of a 57-year-old male patient who developed fulminant pulmonary
      embolism following heparin-induced thrombosis without thrombocytopenia after off
      pump coronary artery bypass surgery.

PMID- 20037106
TI  - Aortic arch reconstruction with an autologous pulmonary arterial-roll tube in an
      interrupted aortic arch.
AB  - We report a case of aortic arch reconstruction with an autologous pulmonary
      arterial-roll tube in a 4-year-old child with a type A interrupted aortic arch.
      The autologous pulmonary arterial-roll tube dilated progressively after the
      operation, and some severe complications occurred, including formation of an
      aneurysm. A second operation was performed to resect the aortic aneurysm and to
      interpose a Dacron tube graft. We conclude that the aforementioned dilation may
      limit the use of an autologous pulmonary arterial-roll tube in the construction
      of the aortic arch.

PMID- 20037107
TI  - Hirudin for management of heparin-induced thrombocytopenia type II in a patient
      with biventricular assist device support.
AB  - A patient with severe dilated cardiomyopathy developed heparin-induced
      thrombocytopenia type II (HIT II) after implantation of a biventricular assist
      device (biVAD). Because the patient showed mild renal dysfunction but severe
      hepatic impairment, the management of anticoagulation was switched from heparin
      to the direct thrombin inhibitor hirudin, which was administered by continuous
      infusion of 0.6 to 1 mg/h. This protocol was monitored by measuring the plasma
      hirudin level, which ranged from 0.5 to 1.5 microg/mL. Unfortunately, the patient
      died on day 22 after implantation from fulminant sepsis caused by Aspergillus
      fumigatus. Neither thromboembolic events nor thrombocytopenia was observed after
      hirudin administration. The explanted biVAD showed no thrombotic material in the
      arterial/venous lines or on the polyurethane valves. We discuss the challenges
      posed by HIT II complicating VAD support as well as its clinical management with
      direct thrombin inhibitors.

PMID- 20037129
TI  - Hyperlipidemia resulting in abnormal density and signal intensity of blood in a
      neonate with lipoprotein lipase deficiency.
AB  - We present the imaging findings in an 8-week-old infant with LPL deficiency. Due
      to markedly increased lipoproteins in the serum, abnormal hypodensity and
      abnormal T1-weighted hyperintensity were identified in the dural venous sinuses
      and medullary veins.

PMID- 20037130
TI  - Comparison of the added value of contrast-enhanced 3D fluid-attenuated inversion
      recovery and magnetization-prepared rapid acquisition of gradient echo sequences
      in relation to conventional postcontrast T1-weighted images for the evaluation of
      leptomeningeal diseases at 3T.
AB  - BACKGROUND AND PURPOSE: The usefulness of contrast-enhanced 3D T2-FLAIR MR
      imaging for the evaluation of leptomeningeal diseases has not been systematically
      investigated. The purpose of this study was to assess the value added by contrast
      enhanced 3D T2-FLAIR and MPRAGE sequences to conventional postcontrast T1
      weighted images in the evaluation of leptomeningeal diseases. We also undertook
      in vitro studies in attempts to understand the consequences of our patient study.
      MATERIALS AND METHODS: Twelve patients with confirmed leptomeningeal diseases
      underwent postcontrast T1-weighted, MPRAGE, and 3D T2-FLAIR imaging at 3T. Two
      radiologists independently assessed the presence of additional information on
      postcontrast 3D MR images compared with postcontrast T1-weighted images. The
      effect of different Gd concentrations and flow velocities on the signal intensity
      on 3D T2-FLAIR images was investigated in vitro. RESULTS: According to both
      reviewers, 3D T2-FLAIR images yielded significantly more information than did
      MPRAGE images (P < .05 and P < .01, respectively). In the in vitro study, 3D T2
      FLAIR was more highly sensitive to low Gd concentrations and less sensitive to
      high Gd concentrations than were T1-weighted or MPRAGE sequences. On 3D T2-FLAIR
      sequences, at a flow velocity exceeding 1.0 cm/s, the signal intensity of blood
      mimicking fluids at concentrations of 0 and 0.1 mmol/L was as low as at 1.3
      mmol/L. CONCLUSIONS: For the depiction of leptomeningeal diseases, postcontrast
      3D T2-FLAIR provides more additional information than postcontrast MPRAGE
      imaging. The superiority of the 3D T2-FLAIR sequence is associated with its high
      sensitivity to flow.

PMID- 20037131
TI  - In vitro evaluation of MR imaging issues at 3T for aneurysm clips made from
      MP35N: Findings and information applied to 155 additional aneurysm clips.
AB  - BACKGROUND AND PURPOSE: Aneurysm clips need to be tested at 3T to characterize MR
      imaging concerns, including magnetic field interactions, MR imaging-related
      heating, and artifacts. Therefore, we evaluated these risks for aneurysm clips.
      MATERIALS AND METHODS: Three different MP35N aneurysm clips (Codman Slim-Line
      Aneurysm Clip, straight, blade length 25-mm; Codman Slim-Line Aneurysm Clip
      Graft, 5-mm diameter x 5-mm width; Codman Slim-Line Aneurysm Clip, reinforcing 30
      degrees angle, 6-mm x 18-mm) that represented the largest mass for 155 additional
      clips made from MP35N were tested. The clips were evaluated at 3T for magnetic
      field interactions, heating, and artifacts. We studied MR imaging-related
      heating, placing the clip in a gelled-saline-filled phantom with MR imaging
      performed by using a transmit/receive radio-frequency body coil at a whole-body
      average SAR of 3 W/kg for 15 minutes. Artifacts were characterized by using T1-SE
      and GRE pulse sequences. RESULTS: Each aneurysm clip showed relatively minor
      magnetic field interactions, which would not cause movement in situ. Heating was
      not excessive (highest temperature change, <1.8 degrees C). Artifacts may create
      problems if the area of interest is in the same area or close to the aneurysm
      clip. CONCLUSIONS: The results of this investigation demonstrated that it would
      be acceptable (ie, "MR conditional" using current terminology) for patients with
      these aneurysm clips to undergo MR imaging at < or =3T. Notably, on the basis of
      the sizes of the clips that underwent testing, these findings pertain to 155
      additional aneurysm clips made from the same material.

PMID- 20037132
TI  - Bevacizumab (Avastin).
AB  - Bevacizumab is a humanized monoclonal antibody that was the first FDA approved
      therapy designed to inhibit angiogenesis. This paper will review the mechanism of
      action and clinical role of this antiangiogenic agent.

PMID- 20037134
TI  - Influenza A encephalopathy, cerebral vasculopathy, and posterior reversible
      encephalopathy syndrome: combined occurrence in a 3-year-old child.
AB  - Encephalopathy is an uncommon complication of childhood influenza infection,
      typically recognized during influenza epidemics. Imaging hallmarks include
      characteristic thalamic lesions, thalamic necrosis and hemispheric edema. We
      describe a child with acute influenza A associated necrotizing encephalopathy
      with MR angiographic evidence of significant cerebral vasculopathy and a
      hemispheric edema pattern consistent with PRES. This case reinforces that
      significant cerebral vasculopathy can accompany influenza infection and that
      influenza is a likely trigger for PRES.

PMID- 20037133
TI  - Non-gaussian analysis of diffusion-weighted MR imaging in head and neck squamous
      cell carcinoma: A feasibility study.
AB  - BACKGROUND AND PURPOSE: Water in biological structures often displays non
      Gaussian diffusion behavior. The objective of this study was to test the
      feasibility of non-Gaussian fitting by using the kurtosis model of the signal
      intensity decay curves obtained from DWI by using an extended range of b-values
      in studies of phantoms and HNSCC. MATERIALS AND METHODS: Seventeen patients with
      HNSCC underwent DWI by using 6 b-factors (0, 50-1500 s/mm(2)) at 1.5T.
      Monoexponential (yielding ADC(mono)) and non-Gaussian kurtosis (yielding apparent
      diffusion coefficient D(app) and apparent kurtosis coefficient K(app)) fits were
      performed on a voxel-by-voxel basis in selected regions of interest (primary
      tumors, metastatic lymph nodes, and spinal cord). DWI studies were also performed
      on phantoms containing either water or homogenized asparagus. To determine
      whether the kurtosis model provided a significantly better fit than did the
      monoexponential model, an F test was performed. Spearman correlation coefficients
      were calculated to assess correlations between K(app) and D(app). RESULTS: The
      kurtosis model fit the experimental data points significantly better than did the
      monoexponential model (P < .05). D(app) was approximately twice the value of
      ADC(mono) (eg, in neck nodal metastases D(app) was 1.54 and ADC(mono) was 0.84).
      K(app) showed a weak Spearman correlation with D(app) in a homogenized asparagus
      phantom and for 44% of tumor lesions. CONCLUSIONS: The use of kurtosis modeling
      to fit DWI data acquired by using an extended b-value range in HNSCC is feasible
      and yields a significantly better fit of the data than does monoexponential
      modeling. It also provides an additional parameter, K(app), potentially with
      added value.

PMID- 20037135
TI  - Erythropoietin promotes functional recovery and enhances nerve regeneration after
      peripheral nerve injury in rats.
AB  - BACKGROUND AND PURPOSE: EPO has been shown to have beneficial effects in a
      variety of CNS injury models. The purpose of this study was to evaluate the
      effects of EPO on nerve regeneration and functional recovery in a rat model of
      peripheral nerve surgery. MATERIALS AND METHODS: The sciatic nerve of the rat
      with a 10-mm defect was bridged with a silicone rubber tube. Forty adult male
      Sprague-Dawley rats were assigned to the control or experimental groups to
      receive an intraperitoneal injection of NGF (2000 U/kg daily for 2 weeks) or EPO
      (5000 U/kg daily for 2 weeks), respectively. Macroscopic, functional,
      electrophysiologic, ultraminiature, and histologic assessments of nerves were
      performed 4-8 weeks after surgery. RESULTS: The results showed that in EPO
      treated rats, there was a significant increase in the axon diameter, myelin
      thickness, and total number of nerve fibers as well as the degree of maturity of
      regenerated myelinated nerve fibers in comparison with those rats not treated
      with EPO. In addition, as measured by the SFI and MNCV, the motor function of the
      re-innervated hind limbs of rats with EPO treatment significantly improved at
      week 8, whereas there was no significant difference in the motor function between
      the 2 groups at 4 weeks. CONCLUSIONS: Our results demonstrated that EPO is able
      to enhance nerve regeneration and promote functional recovery after peripheral
      nerve injury in the rat, suggesting the potential clinical application of EPO for
      the treatment of peripheral nerve injury in humans.

PMID- 20037136
TI  - Usefulness of percutaneously injected ethylene-vinyl alcohol copolymer in
      conjunction with standard endovascular embolization techniques for preoperative
      devascularization of hypervascular head and neck tumors: technique, initial
      experience, and correlation with surgical observations.
AB  - BACKGROUND AND PURPOSE: Few reports have described the embolization of head and
      neck lesions by using direct percutaneous techniques. We report our preliminary
      experience in the direct percutaneous embolization of hypervascular head and neck
      tumors by using Onyx in conjunction with standard endovascular embolization
      techniques. We describe the technical aspects of the procedure and its efficacy
      in reducing intraoperative blood loss. MATERIALS AND METHODS: We retrospectively
      studied 14 patients (3 females and 11 males; mean age, 33.4 years; range, 11-56
      years) with 15 hypervascular tumors of the head and neck that underwent direct
      percutaneous embolization with Onyx in conjunction with particulate embolization.
      Nine paragangliomas and 6 JNAs underwent treatment. Documented blood loss was
      obtained from operative reports in these 15 patients with surgical resection
      performed 24-48 hours after the embolization. RESULTS: Intratumoral penetration
      with progressive blood flow stasis was achieved during each injection. A mean of
      3.1 needles (20-gauge, 3.5-inch spinal needle) were placed percutaneously into
      the lesion (range, 1-6). The mean intraoperative blood loss was 780 mL (range,
      <50-2200 mL). Near total angiographic devascularization was achieved in 13 of 15
      tumors. There were no local complications or neurologic deficits from the
      percutaneous access or embolization of these hypervascular tumors. CONCLUSIONS:
      In this study, the use of percutaneous injected Onyx in conjunction with standard
      endovascular embolization techniques in patients with hypervascular head and neck
      tumors seemed to enhance the ability to devascularize these tumors before
      operative removal.

PMID- 20037137
TI  - Pitfalls in the use of voxel-based morphometry as a biomarker: examples from
      huntington disease.
AB  - BACKGROUND AND PURPOSE: VBM is increasingly used in the study of
      neurodegeneration, and recently there has been interest in its potential as a
      biomarker. However, although it is largely "automated," VBM is rarely implemented
      consistently across studies, and changing user-specified options can alter the
      results in a way similar to the very biologic differences under investigation.
      MATERIALS AND METHODS: This work uses data from patients with HD to demonstrate
      the effects of several user-specified VBM parameters and analyses: type and level
      of statistical correction, modulation, smoothing kernel size, adjustment for
      brain size, subgroup analysis, and software version. RESULTS: The results
      demonstrate that changing these options can alter results in a way similar to the
      biologic differences under investigation. CONCLUSIONS: If VBM is to be useful
      clinically or considered for use as a biomarker, there is a need for greater
      recognition of these issues and more uniformity in its application for the method
      to be both reproducible and valid.

PMID- 20037138
TI  - Effects of FoxO4 overexpression on cholesterol biosynthesis, triacylglycerol
      accumulation, and glucose uptake.
AB  - The Forkhead transcription factors FoxO1, FoxO3a, and FoxO4 play a prominent role
      in regulating cell survival and cell cycle. Whereas FOXO1 was shown to mediate
      insulin sensitivity and adipocyte differentiation, the role of the transcription
      factor FoxO4 in metabolism remains ill defined. To uncover the effects of FoxO4,
      we generated a cellular model of stable FoxO4 overexpression and subjected it to
      microarray-based gene expression profiling. While pathway analysis revealed a
      disruption of cholesterol biosynthesis gene expression, biochemical studies
      revealed an inhibition of cholesterol biosynthesis, which was coupled with
      decreased mRNA levels of lanosterol 14alpha demethylase (CYP51). FoxO4-mediated
      repression of CYP51 led to the accumulation of 24,25 dihydrolano-sterol (DHL),
      which independently and unlike lanosterol inhibited cholesterol biosynthesis.
      Furthermore, FoxO4-overexpressing cells accumulated lipid droplets and
      triacylglycerols and had an increase in basal glucose uptake. Recapitulation of
      these effects was obtained following treatment with CYP51 inhibitors, which also
      induce DHL buildup. Moreover, DHL but not lanosterol strongly stimulated liver X
      receptor alpha (LXRalpha) activity, suggesting that DHL and LXRalpha mediate the
      downstream effects initiated by FoxO4. Together, these studies suggest that FoxO4
      acts on CYP51 to regulate the late steps of cholesterol biosynthesis.

PMID- 20037139
TI  - Ligand trapping by cytochrome c oxidase: implications for gating at the catalytic
      center.
AB  - Cytochrome c oxidase is a member of the heme-copper family of oxygen reductases
      in which electron transfer is linked to the pumping of protons across the
      membrane. Neither the redox center(s) associated with proton pumping nor the
      pumping mechanism presumably common to all heme-copper oxidases has been
      established. A possible conformational coupling between the catalytic center
      (Fe(a3)(3+)-Cu(B)(2+)) and a protein site has been identified earlier from ligand
      binding studies, whereas a structural change initiated by azide binding to the
      protein has been proposed to facilitate the access of cyanide to the catalytic
      center of the oxidized bovine enzyme. Here we show that cytochrome oxidase
      pretreated with a low concentration of azide exhibits a significant increase in
      the apparent rate of cyanide binding relative to that of free enzyme. However,
      this increase in rate does not reflect a conformational change enhancing the
      rapid formation of a Fe(a3)(3+)-CN-Cu(B)(2+) complex. Instead the cyanide-induced
      transition of a preformed Fe(a3)(3+)-N(3)-Cu(B)(2+) to the ternary complex of
      Fe(a3)(3+)-N(3) Cu(B)(2+)-CN is the most likely reason for the observed
      acceleration. Significantly, the slow rate of azide release from the ternary
      complex indicates that cyanide ligated to Cu(B) blocks a channel between the
      catalytic site and the solvent. The results suggest that there is a pathway that
      originates at Cu(B) and that, during catalysis, ligands present at this copper
      center control access to the iron of heme a(3) from the bulk medium.

PMID- 20037140
TI  - The human carnitine transporter SLC22A16 mediates high affinity uptake of the
      anticancer polyamine analogue bleomycin-A5.
AB  - Bleomycin is used in combination with other antineoplastic agents to effectively
      treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the
      cervix, head, and neck. However, resistance to bleomycin remains a persistent
      limitation in exploiting the full therapeutic benefit of the drug with other
      types of cancers. Previously, we documented that the Saccharomyces cerevisiae L
      carnitine transporter Agp2 is responsible for the high affinity uptake of
      polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that
      the human L-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved
      in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human
      testicular cancer cells, which highly express hCT2, are extremely sensitive to
      bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable
      hCT2 expression or MCF-7 human breast cancer cells that only weakly express the
      permease showed striking resistance to the drug. NT2/D1 cells accumulated
      fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116
      cells. Moreover, L-carnitine protected NT2/D1 cells from the lethal effects of
      bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced
      resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2
      overexpression induced by transient transfection of a functional hCT2-GFP fusion
      protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly
      suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the
      rate of bleomycin-A5 accumulation may account for the differential response to
      the drug in patients.

PMID- 20037141
TI  - Inhibition of ERK1/2 and activation of liver X receptor synergistically induce
      macrophage ABCA1 expression and cholesterol efflux.
AB  - ATP-binding cassette transporter A1 (ABCA1), a molecule mediating free
      cholesterol efflux from peripheral tissues to apoAI and high density lipoprotein
      (HDL), inhibits the formation of lipid-laden macrophage/foam cells and the
      development of atherosclerosis. ERK1/2 are important signaling molecules
      regulating cellular growth and differentiation. The ERK1/2 signaling pathway is
      implicated in cardiac development and hypertrophy. However, the role of ERK1/2 in
      the development of atherosclerosis, particularly in macrophage cholesterol
      homeostasis, is unknown. In this study, we investigated the effects of ERK1/2
      activity on macrophage ABCA1 expression and cholesterol efflux. Compared with a
      minor effect by inhibition of other kinases, inhibition of ERK1/2 significantly
      increased macrophage cholesterol efflux to apoAI and HDL. In contrast, activation
      of ERK1/2 reduced macrophage cholesterol efflux and ABCA1 expression. The
      increased cholesterol efflux by ERK1/2 inhibitors was associated with the
      increased ABCA1 levels and the binding of apoAI to cells. The increased ABCA1 by
      ERK1/2 inhibitors was due to increased ABCA1 mRNA and protein stability. The
      induction of ABCA1 expression and cholesterol efflux by ERK1/2 inhibitors was
      concentration-dependent. The mechanism study indicated that activation of liver X
      receptor (LXR) had little effect on ERK1/2 expression and activation. ERK1/2
      inhibitors had no effect on macrophage LXRalpha/beta expression, whereas they did
      not influence the activation or the inhibition of the ABCA1 promoter by LXR or
      sterol regulatory element-binding protein (SREBP). However, inhibition of ERK1/2
      and activation of LXR synergistically induced macrophage cholesterol efflux and
      ABCA1 expression. Our data suggest that ERK1/2 activity can play an important
      role in macrophage cholesterol trafficking.

PMID- 20037142
TI  - Effects of phosphorus supply on growth, phosphate concentration and cluster-root
      formation in three Lupinus species.
AB  - BACKGROUND AND AIMS: In some lupin species, phosphate deficiency induces cluster
      root formation, which enhances P uptake by increasing root surface area and, more
      importantly, the release of root exudates which enhances P availability. METHODS:
      Three species of Lupinus, L. albus, L. atlanticus and L. micranthus, with
      inherently different relative growth rates were cultivated under hydroponics in a
      greenhouse at four phosphate concentrations (1, 10, 50 and 150 microm) to compare
      the role of internal P in regulating cluster-root formation. KEY RESULTS: The
      highest growth rate was observed in L. atlanticus, followed by L. albus and L.
      micranthus. At 1 microm P, cluster-root formation was markedly induced in all
      three species. The highest P uptake and accumulation was observed in L.
      micranthus, followed by L. atlanticus and then L. albus. Inhibition of cluster
      root formation was severe at 10 microm P in L. atlanticus, but occurred stepwise
      with increasing P concentration in the root medium in L. albus. CONCLUSIONS: In
      L. atlanticus and L. albus cluster-root formation was suppressed by P treatments
      above 10 microm, indicating a P-inducible regulating system for cluster-root
      formation, as expected. By contrast, production of cluster roots in L.
      micranthus, in spite of a high internal P concentration, indicated a lower
      sensitivity to P status, which allowed P-toxicity symptoms to develop.

PMID- 20037143
TI  - Both cultured and freshly isolated adipose tissue-derived stem cells enhance
      cardiac function after acute myocardial infarction.
AB  - AIMS: We assessed whether freshly isolated human adipose tissue-derived cells
      (fhADCs) or cultured human adipose tissue-derived stem cells (hASCs) have
      beneficial effects on cardiac function after myocardial infarction (MI), whether
      the injected cells can survive long term, and whether their effects result from
      direct differentiation or paracrine mechanisms. METHODS AND RESULTS: Myocardial
      infarction was experimentally induced in severe combined immunodeficient mice,
      and either fhADCs, cultured hASCs, or phosphate-buffered saline was injected into
      the peri-infarct region. Myocardial function improved significantly in mice
      treated with hASCs or fhADCs 4 weeks after MI. Immunofluorescence revealed that
      grafted hASCs and fhADCs underwent cardiomyogenic differentiation pathway, as
      indicated by expression of connexin 43 and troponin I in a fusion-independent
      manner. Some of the injected cells integrated with host cardiomyocytes through
      connexin 43, and others were incorporated into newly formed vessels. Human
      adipose tissue-derived stem cells survived in injured hearts up to 4 months, as
      detected by luciferase-based bioluminescence imaging. Vascular density was
      significantly increased, and fewer apoptotic cells were present in the peri
      infarct region of cell-injected mice. CONCLUSION: This is the first study to
      systematically compare the effects of fhADCs and hASCs on myocardial
      regeneration. Both cell types engraft into infarcted myocardium, survive, and
      improve myocardial function, suggesting that fhADCs, like hASCs, are a promising
      alternative cell source for myocardial repair after MI.

PMID- 20037144
TI  - A better echocardiographic view to aortic dissection.

PMID- 20037145
TI  - Prosthesis-patient mismatch after transcatheter aortic valve implantation with
      the Medtronic-Corevalve bioprosthesis.
AB  - AIMS: Prosthesis-patient mismatch (P-PM) is an important determinant of morbidity
      and mortality following open aortic valve replacement. The aims of this study
      were to report its incidence and determinants following transcatheter aortic
      valve implantation (TAVI) with the Corevalve bioprosthesis, which have-thus far
      not been described. METHODS AND RESULTS: Patients with severe calcific aortic
      stenosis received TAVI with the Corevalve bioprosthesis via transfemoral route.
      Following TAVI, moderate P-PM was defined as indexed aortic valve effective
      orifice area (AVAi) < or =0.85 cm(2)/m(2) and severe P-PM as AVAi < or =0.65
      cm(2)/m(2). Clinical, echocardiographic, and procedural factors relating to P-PM
      were studied. Optimal device position was defined on fluoroscopy as final
      position of the proximal aspect of the Corevalve stent frame 5-10 mm below the
      native aortic annulus. Between January 2007 and January 2009, 50 consecutive
      patients underwent TAVI in a single centre with the Corevalve bioprosthesis. Mean
      age was 82.8 years (SD 5.9; 70-93) and 48% were male. P-PM occurred in 16 of 50
      cases (32%). Optimal position was achieved in 50% of cases. P-PM was unrelated to
      age, annulus size, LVOT size, Corevalve size, aortic angulation, ejection
      fraction, and sex. It was inversely correlated to optimal position (Spearman rho
      r = -0.34, P = 0.015). Those with optimal positioning had a 16% incidence of P-PM
      relative to 48% of those with suboptimal positioning (Pearson chi(2) P = 0.015).
      CONCLUSION: The incidence of P-PM following TAVI with the Corevalve bioprosthesis
      is compared favourably with that seen after AVR with conventional open stented
      bioprostheses and its occurrence is influenced by device positioning.

PMID- 20037147
TI  - Cultured and freshly isolated adipose tissue-derived cells: fat years for cardiac
      stem cell therapy.

PMID- 20037146
TI  - Cardio-renal syndromes: report from the consensus conference of the acute
      dialysis quality initiative.
AB  - A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy,
      in September 2008 under the auspices of the Acute Dialysis Quality Initiative
      (ADQI). The following topics were matter of discussion after a systematic
      literature review and the appraisal of the best available evidence:
      definition/classification system; epidemiology; diagnostic criteria and
      biomarkers; prevention/protection strategies; management and therapy. The
      umbrella term CRS was used to identify a disorder of the heart and kidneys
      whereby acute or chronic dysfunction in one organ may induce acute or chronic
      dysfunction in the other organ. Different syndromes were identified and
      classified into five subtypes. Acute CRS (type 1): acute worsening of heart
      function (AHF-ACS) leading to kidney injury and/or dysfunction. Chronic cardio
      renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD)
      leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type
      3): acute worsening of kidney function (AKI) leading to heart injury and/or
      dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease
      leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5):
      systemic conditions leading to simultaneous injury and/or dysfunction of heart
      and kidney. Consensus statements concerning epidemiology, diagnosis, prevention,
      and management strategies are discussed in the paper for each of the syndromes.

PMID- 20037148
TI  - Impact of contrast-enhanced echocardiography on the diagnostic algorithm of acute
      aortic dissection.
AB  - AIMS: To determine the usefulness of contrast echocardiography in the diagnosis
      of aortic dissection (AD) and in the assessment of findings necessary for
      adequate patient management. METHODS AND RESULTS: Conventional and contrast
      enhanced transthoracic echocardiography (TTE) and transoesophageal
      echocardiography (TOE) were performed in 128 consecutive patients with clinically
      suspected acute AD. Results were validated independently against intraoperative
      findings in 45 patients and computed tomography information in 83. Sensitivity
      and specificity of conventional TTE increased after contrast enhancement from
      73.7 to 86.8% (P< 0.005) and 71.2 to 90.4% (P < 0.05), respectively. Sensitivity
      and specificity of enhanced TTE were similar to conventional TOE in ascending
      aorta (93.3 vs. 95.6% and 97.6 vs. 96.4%, respectively) and in the arch (88.4 vs.
      93.0% and 95.3 vs. 98.82%, respectively). Contrast-enhanced TOE permitted the
      location of non-visualized entry tear in seven cases (10.6%), helped to correctly
      identify the true lumen in six (9.1%), and diagnosed retrograde dissection in
      nine (13.6%). CONCLUSION: Contrast enhancement substantially improves TTE in the
      diagnosis of AD and should be considered as the initial imaging modality in the
      emergency setting. Contrast enhancement also has significant value for obtaining
      critical morphological and haemokinetic information by TOE useful for adequate
      patient management.

PMID- 20037149
TI  - Awake light-aided blind nasal intubation: prototype device.
AB  - BACKGROUND: Limited mouth opening associated with unavailable or ineffective
      fibreoptic bronchoscope (FOB) is an intubation challenge. A light-aiding device
      may facilitate the blind nasal intubation. METHODS: Awake blind nasal intubation
      was planned for 16 elective patients with inaccessible oral route (three children
      and 13 adults, ASA I-II). Topical anaesthesia for the supraglottis, glottis, and
      upper trachea was performed using prototype supraglottic topical anaesthesia
      device and cricothyroid injection of local anaesthesia. Hand-made light-aiding
      intubation device was used to help blind nasal intubation. Three attempts of
      blind nasal intubation (60 s each) were allowed, otherwise failure and FOB
      intubation were considered. During the procedure, heart rate, mean arterial
      pressure, and arterial oxygen saturation (Spa(o(2))) were measured. Temperature
      created at the bulb surface of the device was measured for 4 min duration, with
      and without exposing the bulb to oxygen flow of 6 litre min(-1). RESULTS: All the
      patients were successfully intubated except one child. Time to intubate in adults
      was mean (sd) 52.7 (8.6) s. Spa(o(2)) showed significant difference between
      before and after procedural values. The maximum temperature recorded at the bulb
      surface was 46.8 (0.4) degrees C and 48.1 (0.8) degrees C with and without oxygen
      flow, respectively. CONCLUSIONS: The device appeared to be a safe and cost
      effective transillumination method for blind nasal intubation in difficult
      airways.

PMID- 20037150
TI  - Effect of increased body mass index and anaesthetic duration on recovery of
      protective airway reflexes after sevoflurane vs desflurane.
AB  - BACKGROUND: Increased BMI may increase the body's capacity to store potent
      inhaled anaesthetics, more so with more soluble agents. Accordingly, we asked
      whether increased BMI and longer anaesthesia prolonged airway reflex recovery.
      METHODS: We measured time from anaesthetic discontinuation until first response
      to command (T1); from response to command until ability to swallow (T2); and from
      anaesthetic discontinuation to recovery of ability to swallow (T3) in 120
      patients within three BMI ranges (18-24, 25-29, and >or=30 kg m(-2)). All
      received sevoflurane or desflurane, delivered via an LMA. RESULTS: T1 and T3
      after sevoflurane exceeded T1 and T3 after desflurane: 6.6 (sd 4.2) vs 4.0 (1.9)
      min (P<0.001), and 14.1 (sd 8.3) vs 6.1 (2.0) min (P<0.0001). T3 correlated more
      strongly with BMI after sevoflurane (28 s per kg m(-2), P=0.02) than desflurane
      (7 s per kg m(-2), P=0.03). Regarding T2, patients receiving sevoflurane with BMI
      >or=30 kg m(-2) were less often able to swallow 2 min after response to command
      than were those with BMI 18-24 or 25-29 kg m(-2) (3/20 vs 10/20 or 9/20, P<0.05).
      Each sevoflurane MAC-hour delayed T3 by 4.5 min (268 s) (R=0.46, P<0.001) whereas
      each desflurane MAC-hour delayed T3 by 0.2 min (16 s) (R=0.10, P=0.44).
      CONCLUSIONS: Prolonged sevoflurane administration and greater BMI delay airway
      reflex recovery. The contribution of BMI to this delay is more pronounced after
      sevoflurane than desflurane.

PMID- 20037151
TI  - Development and validation of a postoperative nausea and vomiting intensity
      scale.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is common and of concern to
      patients and clinicians. The effect of PONV can range from trivial and transient
      to major clinical importance, and it is unclear which of its characteristics lead
      to discomfort and distress. METHODS: We first enrolled 180 participants
      (patients, family members, nurses, doctors) to identify the characteristics of
      clinically important PONV, and from these data developed a measurement scale. We
      then evaluated the scale in a further 163 patients reporting PONV. Validity,
      reliability, and responsiveness of the PONV Intensity Scale were tested using
      psychometric techniques. RESULTS: Most participants agreed that three or more
      vomits, and greater nausea severity and duration, were key factors in defining
      clinically important PONV. These data were used to derive a PONV Intensity Scale
      and a score to define clinically important PONV. The scale identified 29 patients
      (18%) as having clinically important PONV. Patients with clinically important
      PONV had a poorer quality of recovery (P<0.0005) and needed twice as much
      antiemetic treatment (P<0.0005). The scale was strongly associated with PONV
      consequences and complications, with odds ratios ranging from 6.0 to 31 (all
      P<0.0005). The scale had excellent reproducibility (intraclass correlation 0.99,
      P<0.0005). The scale could reliably reflect a clinically important change in
      health status (effect size 0.82, P<0.0005). CONCLUSIONS: The PONV Intensity Scale
      is a valid, reliable, and responsive measure of clinically important PONV.

PMID- 20037152
TI  - Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular
      domain.
AB  - Zinc is an essential trace element and plays crucial roles in normal development,
      often as an integral structural component of transcription factors and enzymes.
      Recent evidence suggests that intracellular Zn(2+) functions as a signaling
      molecule, mediating a variety of important physiological phenomena. However, the
      immediate effectors of intracellular Zn(2+) signaling are not well known. We show
      here that intracellular Zn(2+) potently and reversibly activates large
      conductance voltage- and Ca(2+)-activated Slo1 K(+) (BK) channels. The full
      effect of Zn(2+) requires His(365) in the RCK1 (regulator of conductance for
      K(+)) domain of the channel. Furthermore, mutation of two nearby acidic residues,
      Asp(367) and Glu(399), also reduced activation of the channel by Zn(2+),
      suggesting a possible structural arrangement for Zn(2+) binding by the
      aforementioned residues. Extracellular Zn(2+) activated Slo1 BK channels when
      coexpressed with Zn(2+)-permeable TRPM7 (transient receptor potential melastatin
      7) channels. The results thus demonstrate that Slo1 BK channels represent a
      positive and direct effector of Zn(2+) signaling and may participate in sculpting
      cellular response to an increase in intracellular Zn(2+) concentration.

PMID- 20037153
TI  - Identification of Thr29 as a critical phosphorylation site that activates the
      human proton channel Hvcn1 in leukocytes.
AB  - Voltage-gated proton channels and NADPH oxidase function cooperatively in
      phagocytes during the respiratory burst, when reactive oxygen species are
      produced to kill microbial invaders. Agents that activate NADPH oxidase also
      enhance proton channel gating profoundly, facilitating its roles in charge
      compensation and pH(i) regulation. The "enhanced gating mode" appears to reflect
      protein kinase C (PKC) phosphorylation. Here we examine two candidates for PKC
      delta phosphorylation sites in the human voltage-gated proton channel, H(V)1
      (Hvcn1), Thr(29) and Ser(97), both in the intracellular N terminus. Channel
      phosphorylation was reduced in single mutants S97A or T29A, and further in the
      double mutant T29A/S97A, by an in vitro kinase assay with PKC-delta. Enhanced
      gating was evaluated by expressing wild-type (WT) or mutant H(V)1 channels in
      LK35.2 cells, a B cell hybridoma. Stimulation by phorbol myristate acetate
      enhanced WT channel gating, and this effect was reversed by treatment with the
      PKC inhibitor GF109203X. The single mutant T29A or double mutant T29A/S97A failed
      to respond to phorbol myristate acetate or GF109203X. In contrast, the S97A
      mutant responded like cells transfected with WT H(V)1. We conclude that under
      these conditions, direct phosphorylation of the proton channel molecule at
      Thr(29) is primarily responsible for the enhancement of proton channel gating.
      This phosphorylation is crucial to activation of the proton conductance during
      the respiratory burst in phagocytes.

PMID- 20037154
TI  - Negative feedback control of osteoclast formation through ubiquitin-mediated down
      regulation of NFATc1.
AB  - The regulation of NFATc1 expression is important for osteoclast differentiation
      and function. Herein, we demonstrate that macrophage-colony-stimulating factor
      induces NFATc1 degradation via Cbl proteins in a Src kinase-dependent manner.
      NFATc1 proteins are ubiquitinated and rapidly degraded during late stage
      osteoclastogenesis, and this degradation is mediated by Cbl-b and c-Cbl ubiquitin
      ligases in a Src-dependent manner. In addition, NFATc1 interacts endogenously
      with c-Src, c-Cbl, and Cbl-b in osteoclasts. Overexpression of c-Src induces down
      regulation of NFATc1, and depletion of Cbl proteins blocks NFATc1 degradation
      during late stage osteoclastogenesis. Taken together, our data provide a negative
      regulatory mechanism by which macrophage-colony-stimulating factor activates Src
      family kinases and Cbl proteins, and subsequently, induces NFATc1 degradation
      during osteoclast differentiation.

PMID- 20037155
TI  - Voltage-dependent anion channel 1-based peptides interact with Bcl-2 to prevent
      antiapoptotic activity.
AB  - The antiapoptotic proteins of the Bcl-2 family are expressed at high levels in
      many types of cancer. However, the mechanism by which Bcl-2 family proteins
      regulate apoptosis is not fully understood. Here, we demonstrate the interaction
      of Bcl-2 with the outer mitochondrial membrane protein, voltage-dependent anion
      channel 1 (VDAC1). A direct interaction of Bcl-2 with bilayer-reconstituted
      purified VDAC was demonstrated, with Bcl-2 decreasing channel conductance.
      Expression of Bcl-2-GFP prevented apoptosis in cells expressing native but not
      certain VDAC1 mutants. VDAC1 sequences and amino acid residues important for
      interaction with Bcl-2 were defined through site-directed mutagenesis. Synthetic
      peptides corresponding to the VDAC1 N-terminal region and selected sequences
      bound specifically, in a concentration- and time-dependent manner, to immobilized
      Bcl-2, as revealed by the real-time surface plasmon resonance. Moreover,
      expression of the VDAC1-based peptides in cells over-expressing Bcl-2 prevented
      Bcl-2-mediated protection against staurosporine-induced apoptotic cell death.
      Similarly, a cell-permeable VDAC1-based synthetic peptide was also found to
      prevent Bcl-2-GFP-mediated protection against apoptosis. These results point to
      Bcl-2 as promoting tumor cell survival through binding to VDAC1, thereby
      inhibiting cytochrome c release and apoptotic cell death. Moreover, these
      findings suggest that interfering with the binding of Bcl-2 to mitochondria by
      VDAC1-based peptides may serve to potentiate the efficacy of conventional
      chemotherapeutic agents.

PMID- 20037156
TI  - Tryptophan in the pore of the mechanosensitive channel MscS: assessment of pore
      conformations by fluorescence spectroscopy.
AB  - Structural changes in channel proteins give critical insights required for
      understanding the gating transitions that underpin function. Tryptophan (Trp) is
      uniquely sensitive to its environment and can be used as a reporter of
      conformational changes. Here, we have used site-directed Trp insertion within the
      pore helices of the small mechanosensitive channel protein, MscS, to monitor
      conformational transitions. We show that Trp can be inserted in place of Leu at
      the two pore seal positions, Leu(105) and Leu(109), resulting in functional
      channels. Using Trp(105) as a probe, we demonstrate that the A106V mutation
      causes a modified conformation in the purified channel protein consistent with a
      more open state in solution. Moreover, we show that solubilized MscS changes to a
      more open conformation in the presence of phospholipids or their lysoforms.

PMID- 20037157
TI  - Role of transmembrane domain 4 in ligand permeation by Crithidia fasciculata
      equilibrative nucleoside transporter 2 (CfNT2).
AB  - Equilibrative nucleoside transporters play essential roles in nutrient uptake,
      cardiovascular and renal function, and purine analog drug chemotherapies. Limited
      structural information is available for this family of transporters; however,
      residues in transmembrane domains 1, 2, 4, and 5 appear to be important for
      ligand and inhibitor binding. In order to identify regions of the transporter
      that are important for ligand specificity, a genetic selection for mutants of the
      inosine-guanosine-specific Crithidia fasciculata nucleoside transporter 2 (CfNT2)
      that had gained the ability to transport adenosine was carried out in the yeast
      Saccharomyces cerevisiae. Nearly all positive clones from the genetic selection
      carried mutations at lysine 155 in transmembrane domain 4, highlighting lysine
      155 as a pivotal residue governing the ligand specificity of CfNT2. Mutation of
      lysine 155 to asparagine conferred affinity for adenosine on the mutant
      transporter at the expense of inosine and guanosine affinity due to weakened
      contacts to the purine ring of the ligand. Following systematic cysteine-scanning
      mutagenesis, thiol-specific modification of several positions within
      transmembrane domain 4 was found to interfere with inosine transport capability,
      indicating that this helix lines the water-filled ligand translocation channel.
      Additionally, the pattern of modification of transmembrane domain 4 suggested
      that it may deviate from helicity in the vicinity of residue 155. Position 155
      was also protected from modification in the presence of ligand, suggesting that
      lysine 155 is in or near the ligand binding site. Transmembrane domain 4 and
      particularly lysine 155 appear to play key roles in ligand discrimination and
      translocation by CfNT2.

PMID- 20037158
TI  - Smad3 protein levels are modulated by Ras activity and during the cell cycle to
      dictate transforming growth factor-beta responses.
AB  - Transforming growth factor beta (TGF-beta) regulates many biological processes,
      and aberrant TGF-beta signaling is implicated in tumor development. Smad3 is a
      central component of the TGF-beta signaling pathway, and once activated, Smad3
      forms complexes with Smad4 or other receptor-regulated Smads, which accumulate in
      the nucleus to transcriptionally regulate TGF-beta target genes. Because Smad3
      plays a significant role in mediating the activities of TGF-beta, we examined its
      regulation during tumor development using a well characterized tumor model. We
      demonstrate that Smad3 levels are dramatically reduced in the tumorigenic cell
      line transformed with activated H-Ras compared with the normal parental
      epithelial cells. Interestingly, we also observe a cell cycle-dependent
      regulation of Smad3 in both cell types, with high Smad3 levels in quiescent cells
      and a significant drop in Smad3 protein levels in proliferating cells. Smad3 is
      regulated at the mRNA level and at the level of protein stability. In addition,
      functional analysis indicates that down-regulation of Smad3 levels is required
      for the tumor cells to proliferate in the presence of TGF-beta, because ectopic
      expression of Smad3 in the tumorigenic cell line restores the growth inhibitory
      response to TGF-beta. In contrast, expression of high levels of Smad3 did not
      interfere with the ability of these cells to undergo epithelial to mesenchymal
      transition upon TGF-beta stimulation. Altogether, our results suggest that the
      level of Smad3 protein is an important determinant of the progression of
      tumorigenesis. High levels of Smad3 are required for the tumor suppressor
      activities of TGF-beta, whereas lower levels are sufficient for the tumor
      promoting functions.

PMID- 20037159
TI  - Gating of the mitochondrial permeability transition pore by long chain fatty acyl
      analogs in vivo.
AB  - The role played by long chain fatty acids (LCFA) in promoting energy expenditure
      is confounded by their dual function as substrates for oxidation and as putative
      classic uncouplers of mitochondrial oxidative phosphorylation. LCFA analogs of
      the MEDICA (MEthyl-substituted DICarboxylic Acids) series are neither esterified
      into lipids nor beta-oxidized and may thus simulate the uncoupling activity of
      natural LCFA in vivo, independently of their substrate role. Treatment of rats or
      cell lines with MEDICA analogs results in low conductance gating of the
      mitochondrial permeability transition pore (PTP), with 10-40% decrease in the
      inner mitochondrial membrane potential. PTP gating by MEDICA analogs is accounted
      for by inhibition of Raf1 expression and kinase activity, resulting in
      suppression of the MAPK/RSK1 and the adenylate cyclase/PKA transduction pathways.
      Suppression of RSK1 and PKA results in a decrease in phosphorylation of their
      respective downstream targets, Bad(Ser-112) and Bad(Ser-155). Decrease in Bad(Ser
      112, Ser-155) phosphorylation results in increased binding of Bad to
      mitochondrial Bcl2 with concomitant displacement of Bax, followed by PTP gating
      induced by free mitochondrial Bax. Low conductance PTP gating by LCFA/MEDICA may
      account for their thyromimetic calorigenic activity in vivo.

PMID- 20037161
TI  - Transforming growth factor-beta-activated kinase 1 is an essential regulator of
      myogenic differentiation.
AB  - Satellite cells/myoblasts account for the majority of muscle regenerative
      potential in response to injury and muscular adaptation to exercise. Although the
      ability to influence this process would provide valuable benefits for treating a
      variety of patients suffering from muscle loss, the regulatory mechanisms of
      myogenesis are not completely understood. We have tested the hypothesis that
      transforming growth factor-beta-activated kinase 1 (TAK1) is an important
      regulator of skeletal muscle formation. TAK1 is expressed in proliferating C2C12
      myoblasts, and its levels are reduced upon differentiation of myoblasts into
      myotubes. In vivo, TAK1 is predominantly expressed in developing skeletal muscle
      of young mice. However, the expression of TAK1 was significantly up-regulated in
      regenerating skeletal muscle of adult mice. Overexpression of a dominant negative
      mutant of TAK1 or knockdown of TAK1 inhibited the proliferation and
      differentiation of C2C12 myoblasts. TAK1 was required for the expression of
      myogenic regulatory factors in differentiating myoblasts. Genetic ablation of
      TAK1 also inhibited the MyoD-driven transformation of mouse embryonic fibroblasts
      into myotubes. Inhibition of TAK1 suppressed the differentiation-associated
      activation of p38 mitogen-activated protein kinase (MAPK) and Akt kinase.
      Overexpression of a constitutively active mutant of MAPK kinase 6 (MKK6, an
      upstream activator of p38 MAPK) but not constitutive active Akt restored the
      myogenic differentiation in TAK1-deficient mouse embryonic fibroblasts. Insulin
      growth factor 1-induced myogenic differentiation was also found to involve TAK1.
      Collectively, our results suggest that TAK1 is an important upstream regulator of
      skeletal muscle cell differentiation.

PMID- 20037160
TI  - Abrogation of glucocorticoid receptor dimerization correlates with dissociated
      glucocorticoid behavior of compound a.
AB  - Compound A (CpdA), a dissociated glucocorticoid receptor modulator, decreases
      corticosteroid-binding globulin (CBG), adrenocorticotropic hormone (ACTH), and
      luteneinizing hormone levels in rats. Whether this is due to transcriptional
      regulation by CpdA is not known. Using promoter reporter assays we show that
      CpdA, like dexamethasone (Dex), directly transrepresses these genes. Results
      using a rat Cbg proximal-promoter reporter construct in BWTG3 and HepG2 cell
      lines support a glucocorticoid receptor (GR)-dependent transrepression mechanism
      for CpdA. However, CpdA, unlike Dex, does not result in transactivation via
      glucocorticoid-responsive elements within a promoter reporter construct even when
      GR is co-transfected. The inability of CpdA to result in transactivation via
      glucocorticoid-responsive elements is confirmed on the endogenous tyrosine
      aminotransferase gene, whereas transrepression ability is confirmed on the
      endogenous CBG gene. Consistent with a role for CpdA in modulating GR activity,
      whole cell binding assays revealed that CpdA binds reversibly to the GR, but with
      lower affinity than Dex, and influences association of [(3)H]Dex, but has no
      effect on dissociation. In addition, like Dex, CpdA causes nuclear translocation
      of the GR, albeit to a lesser degree. Several lines of evidence, including
      fluorescence resonance energy transfer, co-immunoprecipitation, and nuclear
      immunofluorescence studies of nuclear localization-deficient GR show that CpdA,
      unlike Dex, does not elicit ligand-induced GR dimerization. Comparison of the
      behavior of CpdA in the presence of wild type GR to that of Dex with a
      dimerization-deficient GR mutant (GR(dim)) strongly supports the conclusion that
      loss of dimerization is responsible for the dissociated behavior of CpdA.

PMID- 20037162
TI  - LXR-SREBP-1c-phospholipid transfer protein axis controls very low density
      lipoprotein (VLDL) particle size.
AB  - Liver X receptors (LXRs) activate triglyceride synthesis in liver directly and
      indirectly by inducing sterol regulatory element-binding protein-1c (SREBP-1c).
      When administered to wild-type mice, the LXR activator T0901317 produces a mild
      and transient hypertriglyceridemia. Here, we show that T0901317 produces massive
      hypertriglyceridemia when given to mice lacking low density lipoprotein (LDL)
      receptors (Ldlr(-/-) mice). Triglycerides ranged from 4000 to 6000 mg/dl, and the
      plasma turned milky. The median diameter of VLDL particles, measured by electron
      microscopy, increased from 43 to 112 nm, 87% exceeding 80 nm, the size of
      chylomicrons. Hypertriglyceridemia was prevented in Ldlr(-/-) recipient mice that
      lacked SREBP-1c (Ldlr(-/-);Srebp-1c(-/-) double knock-out mice). In Ldlr(-/-)
      mice, T0901317 increased mRNAs not only for enzymes of fatty acid and
      triglyceride synthesis, but also for phospholipid transfer protein (PLTP), which
      transfers phospholipids into nascent VLDL, allowing particle expansion. The PLTP
      increase was blunted in Ldlr(-/-);Srebp-1c(-/-) animals. When Ldlr(-/-);Srebp-1c(
      /-) mice received an adenovirus encoding Pltp, the hypertriglyceridemic response
      to T0901317 was partially restored and the VLDL size increased. We conclude that
      LXR agonists activate triglyceride synthesis and Pltp transcription by activating
      Srebp-1c. In concert with the increase in TG synthesis, the increased PLTP
      permits triglyceride incorporation into abnormally large VLDL, which are removed
      from plasma by LDL receptors. In the absence of LDL receptors, the large VLDLs
      accumulate and produce massive hypertriglyceridemia.

PMID- 20037163
TI  - Cell-penetrating peptides with intracellular actin-remodeling activity in
      malignant fibroblasts.
AB  - Cell-penetrating peptides can cross cell membranes and are commonly seen as
      biologically inert molecules. However, we found that some cell-penetrating
      peptides could remodel actin cytoskeleton in oncogene-transformed NIH3T3/EWS-Fli
      cells. These cells have profound actin disorganization related to their tumoral
      transformation. These arginine- and/or tryptophan-rich peptides could cross cell
      membrane and induce stress fiber formation in these malignant cells, whereas they
      had no perceptible effect in non-tumoral fibroblasts. In addition, motility
      (migration speed, random motility coefficient, wound healing) of the tumor cells
      could be decreased by the cell-permeant peptides. Although the peptides
      differently influenced actin polymerization in vitro, they could directly bind
      monomeric actin as determined by NMR and calorimetry studies. Therefore, cell
      penetrating peptides might interact with intracellular protein partners, such as
      actin. In addition, the fact that they could reverse the tumoral phenotype is of
      interest for therapeutic purposes.

PMID- 20037165
TI  - Increasing evidence base for sodium bicarbonate therapy to prevent contrast media
      induced acute kidney injury: little role of unpublished studies.

PMID- 20037164
TI  - Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin
      regulates cardiac growth and function.
AB  - Calcineurin is a protein phosphatase that is uniquely regulated by sustained
      increases in intracellular Ca(2+) following signal transduction events.
      Calcineurin controls cellular proliferation, differentiation, apoptosis, and
      inducible gene expression following stress and neuroendocrine stimulation. In the
      adult heart, calcineurin regulates hypertrophic growth of cardiomyocytes in
      response to pathologic insults that are associated with altered Ca(2+) handling.
      Here we determined that calcineurin signaling is directly linked to the proper
      control of cardiac contractility, rhythm, and the expression of Ca(2+)-handling
      genes in the heart. Our approach involved a cardiomyocyte-specific deletion using
      a CnB1-LoxP-targeted allele in mice and three different cardiac-expressing Cre
      alleles/transgenes. Deletion of calcineurin with the Nkx2.5-Cre knock-in allele
      resulted in lethality at 1 day after birth due to altered right ventricular
      morphogenesis, reduced ventricular trabeculation, septal defects, and valvular
      overgrowth. Slightly later deletion of calcineurin with the alpha-myosin heavy
      chain Cre transgene resulted in lethality in early mid adulthood that was
      characterized by substantial reductions in cardiac contractility, severe
      arrhythmia, and reduced myocyte content in the heart. Young calcineurin heart
      deleted mice died suddenly after pressure overload stimulation or neuroendocrine
      agonist infusion, and telemetric monitoring of older mice showed arrhythmia
      leading to sudden death. Mechanistically, loss of calcineurin reduced expression
      of key Ca(2+)-handling genes that likely lead to arrhythmia and reduced
      contractility. Loss of calcineurin also directly impacted cellular proliferation
      in the postnatal developing heart. These results reveal multiple mechanisms
      whereby calcineurin regulates cardiac development and myocyte contractility.

PMID- 20037166
TI  - Inhibition of nuclear factor kappa B attenuates tumour progression in an animal
      model of renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a highly metastatic and lethal disease
      with few efficacious treatments. Many studies have shown that the ubiquitous
      transcription factor nuclear factor kappa B (NF-kappaB) plays a key role in the
      development and progression of many cancers including RCC. The aim of this
      investigation was to evaluate the anti-cancer effect of pyrrolidine
      dithiocarbamate (PDTC), a NF-kappaB inhibitor, in a murine xenograft model of
      RCC. METHODS: The metastatic human RCC cell line, SN12K1, was inoculated into the
      left kidneys of severe combined immunodeficiency mice and the effect of semi
      continuous PDTC treatment (50 mg/kg) on RCC growth analysed 5 weeks later. The
      analyses carried out in three groups (no treatment, RCC alone and RCC + PDTC) at
      5 weeks were: renal weight, protein expression by immunohistochemistry and
      Western immunoblot, apoptosis (TdT-mediated nick end labelling and morphology)
      and mitosis (morphology). RESULTS: PDTC significantly decreased RCC growth and
      the expression of NF-kappaB subunits (p50, p52, c-Rel and RelB), upstream IKK
      beta and IKK-gamma, but did not induce any changes in the expression of IkappaB
      alpha and IkappaB-beta. RCC growth was associated with a significant decrease in
      the expression of the anti-apoptotic proteins Bcl-2 and Bcl-(XL) and increase in
      pro-apoptotic Bax, all of which were reversed by PDTC. Cell proliferation was
      significantly reduced by PDTC. CONCLUSION: The results demonstrate the potential
      anti-cancer benefits of treating NF-kappaB positive RCCs with NF-kappaB
      inhibitors like PDTC.

PMID- 20037167
TI  - Health-related quality of life in patients with type 1 diabetes--association with
      diabetic complications (the FinnDiane Study).
AB  - BACKGROUND: The daily treatment of type 1 diabetes with frequent monitoring of
      blood glucose levels and nuisance caused by insulin administration may affect
      patients' health-related quality of life (HRQoL). Type 1 diabetes is further
      burdened with an increased risk of complications which may additionally reduce a
      patient's HRQoL. We aimed to assess HRQoL and its association with diabetic
      complications in a large sample of patients with type 1 diabetes. METHODS:
      Altogether, 1070 patients with type 1 diabetes (46% men, mean age 46 +/- 12
      years, diabetes duration 29 +/- 13 years) from the Finnish Diabetic Nephropathy
      Study (FinnDiane Study) participated in this cross-sectional study. Data on HRQoL
      were obtained from 1023 patients using the 15D instrument. When studying
      nephropathy, patients were divided into groups based on their albumin excretion
      rate. Laser-treated patients were classified as having proliferative retinopathy.
      RESULTS: The mean 15D score was 0.899 +/- 0.095 with no differences between men
      and women. HRQoL decreased with increasing age among patients with and without
      diabetic complications. In the Tobit regression model, macroalbuminuria (-0.036),
      dialysis (-0.082), renal transplant (-0.053), poor glycemic control (-0.006),
      ageing (-0.002) and longer diabetes duration (-0.001) explained the reduction in
      HRQoL. In a corresponding model, the presence of proliferative retinopathy did
      not have a significant negative influence on HRQoL. Of individual dimensions of
      the 15D instrument, nephropathy affected all but five dimensions, while
      retinopathy affected vision, mobility, eating and usual activities. CONCLUSIONS:
      The 15D scores decreased with increasing age. The presence of nephropathy, but
      not retinopathy, reduced the subjective HRQoL in patients with type 1 diabetes.

PMID- 20037168
TI  - Fibroblast growth factor-23 and early decrements in kidney function: the Heart
      and Soul Study.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23) is associated with mortality in
      dialysis patients, and concentrations are elevated in moderate chronic kidney
      disease (CKD). The threshold of CKD or albuminuria at which FGF-23 begins to
      change is unknown. METHODS: In 792 outpatients with stable cardiovascular disease
      (CVD) and normal kidney function to moderate CKD, we evaluate the associations of
      estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR)
      with plasma FGF-23 concentrations. RESULTS: Compared to participants with eGFR
      >or=90 ml/min/1.73 m(2), mean FGF-23 concentrations were 7.8 RU/ml higher (4.3
      11.5, P = 0.01) in those with eGFR 60-89 ml/min/1.73 m(2) in models adjusted for
      age, sex, race, ACR, blood pressure, diabetes and body mass index. More advanced
      decrements in eGFR were associated with much higher FGF-23 concentrations. In
      spline analysis, the slope of change in FGF-23 concentration was evident at eGFR
      <90 ml/min/1.73 m(2). Compared to participants with ACR <30 mg/g, mean FGF-23
      concentrations were 18.4 RU/ml higher (9.3-29.2, P < 0.001) in those with ACR 30
      299 mg/g in models adjusted for identical covariates plus eGFR and much higher in
      individuals with ACR >or=300 mg/g. Spline analysis demonstrated a linear
      relationship of ACR with FGF-23, independent of eGFR, even among persons with ACR
      <30 mg/g. CONCLUSION: Modest decrements in eGFR or elevations in albuminuria are
      each independently associated with higher FGF-23 concentrations in outpatients
      with stable CVD.

PMID- 20037169
TI  - Incidence and outcome of patients starting renal replacement therapy for end
      stage renal disease due to multiple myeloma or light-chain deposit disease: an
      ERA-EDTA Registry study.
AB  - BACKGROUND: Information on demographics and survival of patients starting renal
      replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple
      myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this
      study was to describe the incidence, characteristics, causes of death and
      survival rates of RRT for ESRD due to MM or LCDD in the ERA-EDTA Registry.
      METHODS: Thirteen national registries providing data on patients who started RRT
      from 1986-2005 to the ERA-EDTA Registry participated. Incidence per million
      population (pmp) of RRT for ESRD due to MM or LCDD and other causes (non-MM) was
      observed overtime. Patient survival on RRT was examined, unadjusted and adjusted
      for age and gender. RESULTS: Of the 159 637 patients on RRT, 2453 (1.54%) had MM
      or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and
      gender, increased from 0.70 pmp in 1986-1990 to 2.52 pmp in 2001-2005. MM and
      LCDD patients compared to non-MM patients were older and a higher percentage was
      on haemodialysis at day 91 after the start of RRT. The most common causes of
      death in MM and LCDD patients were malignancy (36.1%), cardiovascular causes
      (17.2%) and infection (14.7%). MM and LCDD patients had a 2.77 (95% CI, 2.65
      2.90) higher risk of death compared to non-MM patients. The unadjusted median
      survival on RRT was 0.91 years in MM and LCDD patients and 4.46 years in non-MM
      patients. During follow-up, 35 patients were transplanted and their mean survival
      was 9.6 years. CONCLUSION: The incidence of RRT for ESRD due to MM or LCDD has
      increased over the past 20 years in Europe. The median patient survival on RRT
      for MM and LCDD patients was 0.91 years, compared to 4.46 years for non-MM
      patients. These results suggest that dialysis, and in selected cases even
      transplantation, should be offered to MM and LCDD patients.

PMID- 20037170
TI  - Albuminuria in non-primary renal disease: risk marker rather than risk factor.

PMID- 20037171
TI  - An unusual case of hyponatraemia.
AB  - The differential diagnosis of hyponatraemia is manifold and includes hormonal
      disorders such as primary adrenal insufficiency or hypothyroidism. The diagnosis
      of adrenal insufficiency is always suggestive in cases of hypotension associated
      with hyponatraemia, hyperkalaemia and metabolic acidosis. We herein report a case
      of severe hyponatraemia in a patient with Addison's disease. The underlying cause
      was disseminated adrenal tuberculosis without any evidence of other organ
      involvement. To date, tuberculosis remains a frequent cause of adrenal
      insufficiency although the pathophysiology of adrenal tropism is poorly
      understood.

PMID- 20037172
TI  - Quality of life predicts risks of end-stage renal disease and mortality in
      patients with chronic kidney disease.
AB  - BACKGROUND: Quality of life (QOL) may be associated with morbidity and survival
      in end-stage renal disease (ESRD), and is considered to be an important outcome
      measure for patients with chronic kidney disease (CKD). However, the prognostic
      role of QOL for survival in CKD remains unclear. We studied the relationship
      between QOL and risks of ESRD and mortality in CKD patients. METHODS: From 1
      January 2007 to 31 December 2007, we prospectively used the Taiwan version of
      World Health Organization Quality-of-Life Questionnaire (Taiwan version) (WHOQOL
      BREF(TW)) with 568 CKD patients at a medical centre in southern Taiwan, and
      patients were followed up for 1-2 years after enrollment. The primary outcome was
      the time to dialysis or death. We used Kaplan-Meier curve and Cox proportional
      hazard model for survival analyses. RESULTS: Of the 568 patients enrolled, 423
      were able to complete the questionnaires, and their data were analysed. The
      median follow-up time was 410 days. Progressive decreases in scores of QOL in all
      domains were noted with decrease in eGFR. In unadjusted analysis, dialysis and
      death were associated with lower scores of total and all four domains of WHOQOL
      BREF(TW). In adjusted analysis, the total scores and scores of both physical and
      psychological domains predicted dialysis and mortality (every 1-point decrease
      hazard ratio (HR): 1.050, 95% CI: 1.008-1.095, P = 0.020; HR: 1.179, CI: 1.033
      1.346, P = 0.014; HR: 1.167, CI: 1.016-1.339, P = 0.028, respectively). The
      adjusted risks of ESRD and mortality also increased in patients in the lowest
      tertile of psychological domain (P < 0.01), and physical domain and total scores
      (P < 0.05). CONCLUSIONS: Physical, psychological and total scores of QOL are
      significantly correlated with increased risks of ESRD and death in CKD patients.
      QOL should be considered as an independent predictor of risks of ESRD and
      mortality.

PMID- 20037173
TI  - N-acetylcysteine attenuates glycerol-induced acute kidney injury by regulating
      MAPKs and Bcl-2 family proteins.
AB  - BACKGROUND: Rhabdomyolysis-induced acute kidney injury (AKI) accounts for about
      10 to 40% of all cases of AKI. It is known that N-acetylcysteine (NAC) is
      effective in various experimental renal injury models; however, little
      information is available about the rat model of glycerol-induced rhabdomyolysis.
      In this study, we hypothesize that NAC plays a renoprotective role via the anti
      apoptotic pathway. METHODS: Male Sprague-Dawley rats were divided into four
      groups: (i) saline control group, (ii) NAC-treated group (N-acetylcysteine) (150
      mg/kg), (iii) glycerol-treated group (50%, 8 ml/kg, IM) and (iv) NAC plus
      glycerol-treated group. Rats were sacrificed at 24 h after glycerol injection,
      and the blood and renal tissues were harvested. RESULTS: Glycerol administration
      caused severe renal dysfunction, which included marked renal oxidative stress,
      significantly increased blood urea nitrogen (BUN) and serum creatinine levels.
      Histopathological findings, such as cast formation and tubular necrosis,
      confirmed renal impairment. We noted a marked activation of extracellular signal
      regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p-38, in the
      glycerol-treated group. We also observed high expression of Bax and Bad but only
      weak expression of Bcl-2 and Bcl-xL in the glycerol-treated group. However, NAC
      pretreatment significantly improved renal function and decreased the activation
      of ERK, JNK, Bax and Bad, whereas it increased Bcl-2 and Bcl-xL. CONCLUSION:
      These results demonstrate that NAC protects against renal dysfunction,
      morphological damage and biochemical changes via the anti-apoptotic pathway in
      the glycerol-induced rhabdomyolysis model in rats.

PMID- 20037174
TI  - Risk factors for developing encapsulating peritoneal sclerosis in the icodextrin
      era of peritoneal dialysis prescription.
AB  - BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an uncommon but
      potentially devastating complication of peritoneal dialysis. We have observed an
      increased incidence in our centre over the last few years. METHODS AND PATIENTS:
      To look at potential risk factors for developing EPS, we reviewed 39 cases
      diagnosed between 2000 and 2009 and compared these with a control group of 71
      patients who had been treated by peritoneal dialysis for a minimum of 4 years.
      Both groups extensively used icodextrin, >80% of patients. RESULTS: Both groups
      had been treated by peritoneal dialysis for a similar time: EPS median 54 months
      (46-87.5), compared to controls 70 (54-79.5). However, more of the EPS group were
      treated with peritoneal cyclers (75% vs 46%, X(2) = 6.86, P = 0.009) and
      prescribed more peritoneal dialysate 14.2 l/day +/- 0.7 vs 10.8 +/- 0.5, P <
      0.0001. Although both groups were fast transporters, those with EPS had higher
      D/P creatinine ratios on peritoneal equilibration testing, 0.84 +/- 0.1 vs 0.77
      +/- 0.1, P < 0.05, and lower peritoneal test ultrafiltration volumes, 193 +/- 26
      ml vs 283 +/- 21 ml, P < 0.05. Discussion. The patients in the EPS group were
      faster transporters, with lower peritoneal equilibration and 24-h ultrafiltration
      volumes, and were exposed to greater volumes of peritoneal dialysates compared to
      peritoneal dialysis vintage controls.

PMID- 20037175
TI  - Evaluating cimetidine for GFR estimation in liver transplant recipients.
AB  - Background. Serum creatinine (Scr)-based equations lack accuracy in predicting
      glomerular filtration rate (GFR) in patients with liver disease. Cimetidine has
      been shown to improve the performance of Scr-based GFR formulae. Methods. We
      evaluated the use of cimetidine on the performance of GFR-estimating equations in
      39 liver transplant recipients. The patients received oral cimetidine (800 mg
      tid) during a 24-h urine collection. The next day, the patients underwent
      radionucleotide GFR (rGFR) determination and Scr was measured for creatinine
      clearance (CrCl) and GFR estimation using the Cockcroft-Gault, Nankivell and
      modified diet in renal disease (MDRD) equations. Data were analysed using the
      Pearson correlation statistic and Bland-Altman plots. Results. The mean rGFR was
      65 +/- 26.4 mL/min. The use of cimetidine increased the bias between rGFR and the
      Nankivell and MDRD equations. The combined root mean square error for the CrCl,
      Cockcroft-Gault, Nankivell and MDRD equations without cimetidine were 20.2, 15.6,
      17.0 and 15.5 and cimetidine-aided were 28.2, 23.2, 23.7 and 24.3, respectively.
      Conclusions. All the tested equations without using cimetidine predicted GFR with
      modest accuracy. The addition of cimetidine decreased the precision and increased
      the bias of all the GFR-estimating equations. In the absence of accurate GFR
      estimating equations, rGFR should be used to monitor kidney function in liver
      transplant recipients.

PMID- 20037177
TI  - The impact of stopping inhibitors of the renin-angiotensin system in patients
      with advanced chronic kidney disease.

PMID- 20037176
TI  - Elevated FGF-23 in a patient with rhabdomyolysis-induced acute kidney injury.
AB  - Rhabdomyolysis-induced acute kidney injury (AKI) is characterized by
      hyperphosphataemia and hypocalcaemia. Despite appropriate secondary elevation of
      parathyroid hormone (PTH) in response to hypocalcaemia, rhabdomyolysis and AKI
      are associated with acute deficiency of 1,25-dihydroxycholecalciferol
      (1,25(OH)(2)D(3)), and yet, the mechanism responsible for such a deficiency
      remains unclear. Fibroblast growth factor 23 (FGF-23), a potent phosphaturic
      hormone that inhibits 25-hydroxyvitamin D(3)-1alpha-hydroxylase, could explain
      the deficiency of 1,25(OH)(2)D(3) in this setting. Here, we document, for the
      first time, elevated levels of FGF-23 in a patient with rhabdomyolysis-induced
      AKI.

PMID- 20037178
TI  - Proteomics analysis of the cardiac myofilament subproteome reveals dynamic
      alterations in phosphatase subunit distribution.
AB  - Myofilament proteins are responsible for cardiac contraction. The myofilament
      subproteome, however, has not been comprehensively analyzed thus far. In the
      present study, cardiomyocytes were isolated from rodent hearts and stimulated
      with endothelin-1 and isoproterenol, potent inducers of myofilament protein
      phosphorylation. Subsequently, cardiomyocytes were "skinned," and the myofilament
      subproteome was analyzed using a high mass accuracy ion trap tandem mass
      spectrometer (LTQ Orbitrap XL) equipped with electron transfer dissociation. As
      expected, a small number of myofilament proteins constituted the majority of the
      total protein mass with several known phosphorylation sites confirmed by electron
      transfer dissociation. More than 600 additional proteins were identified in the
      cardiac myofilament subproteome, including kinases and phosphatase subunits. The
      proteomic comparison of myofilaments from control and treated cardiomyocytes
      suggested that isoproterenol treatment altered the subcellular localization of
      protein phosphatase 2A regulatory subunit B56alpha. Immunoblot analysis of
      myocyte fractions confirmed that beta-adrenergic stimulation by isoproterenol
      decreased the B56alpha content of the myofilament fraction in the absence of
      significant changes for the myosin phosphatase target subunit isoforms 1 and 2
      (MYPT1 and MYPT2). Furthermore, immunolabeling and confocal microscopy revealed
      the spatial redistribution of these proteins with a loss of B56alpha from Z-disc
      and M-band regions but increased association of MYPT1/2 with A-band regions of
      the sarcomere following beta-adrenergic stimulation. In summary, we present the
      first comprehensive proteomics data set of skinned cardiomyocytes and demonstrate
      the potential of proteomics to unravel dynamic changes in protein composition
      that may contribute to the neurohormonal regulation of myofilament contraction.

PMID- 20037179
TI  - Patients with severe psoriasis are at increased risk of cardiovascular mortality:
      cohort study using the General Practice Research Database.
AB  - AIMS: Psoriasis is a common chronic inflammatory T-helper cell-1/17 mediated skin
      disease. Recent studies suggest that psoriasis, particularly if severe, may be an
      independent risk factor for atherosclerosis, myocardial infarction (MI), and
      stroke. We conducted a cohort study using the General Practice Research Database
      to determine if severe psoriasis patients have an increased risk of
      cardiovascular (CV) mortality. METHODS AND RESULTS: Severe psoriasis was defined
      as patients who received a psoriasis diagnosis and systemic therapy consistent
      with severe psoriasis (n = 3603). Up to four unexposed patients without psoriasis
      were selected from the same practices and start dates for each psoriasis patient
      (n = 14 330). For every death, the cause was determined by review of the
      electronic medical record. Severe psoriasis was an independent risk factor for CV
      mortality (HR 1.57; 95% CI 1.26, 1.96) when adjusting for age, sex, smoking,
      diabetes, hypertension, and hyperlipidaemia. Overall, severe psoriasis patients
      experienced one extra CV death per 283 patients per year, even when adjusting for
      major CV risk factors. The relative risk of CV mortality was modified by age. For
      example, the RR of CV death for a 40-year-old and 60-year-old with severe
      psoriasis was 2.69 (1.45, 4.99) and 1.92 (1.41, 2.62), respectively. The findings
      were robust to multiple sensitivity analyses. CONCLUSION: Patients with severe
      psoriasis have an increased risk of CV mortality that is independent of
      traditional CV risk factors. Additional studies are needed to determine the
      mechanism of this association and the impact that control of psoriasis has on CV
      risk.

PMID- 20037180
TI  - Acute kidney injury following transcatheter aortic valve implantation: predictive
      factors, prognostic value, and comparison with surgical aortic valve replacement.
AB  - AIMS: Very few data exist on the occurrence of acute kidney injury (AKI)
      associated with transcatheter aortic valve implantation (TAVI). The objectives of
      the present study were (i) to determine the incidence, predictive factors, and
      prognostic value of AKI following TAVI, and (ii) to compare the occurrence of AKI
      in TAVI vs. surgical aortic valve replacement (SAVR) in patients with pre
      procedural chronic kidney disease (CKD). METHODS AND RESULTS: A total of 213
      patients (mean age 82 +/- 8 years) undergoing TAVI for the treatment of severe
      aortic stenosis were included in the study. Acute kidney injury was defined as a
      reduction of >25% in estimated glomerular filtration rate (eGFR) within 48 h
      following the procedure or the need for haemodialysis during index
      hospitalization. Those patients with pre-procedural CKD (eGFR <60 mL/min/1.73
      m(2), n = 119) were compared with 104 contemporary patients with CKD who
      underwent isolated SAVR. The incidence of AKI following TAVI was 11.7%, with 1.4%
      of the patients requiring haemodialysis. Predictive factors of AKI were
      hypertension (OR: 4.66; 95% CI: 1.04-20.87), chronic obstructive pulmonary
      disease (OR: 2.64, 95% CI: 1.10-6.36), and peri-operative blood transfusion (OR:
      3.47, 95% CI: 1.30-9.29). Twenty-one patients (9.8%) died during index
      hospitalization, and the logistic EuroSCORE (OR: 1.03 for each increase of 1%;
      95% CI: 1.01-1.06) and occurrence of AKI (OR: 4.14, 95% CI: 1.42-12.13) were
      identified as independent predictors of postoperative mortality. Patients with
      CKD who underwent TAVI were older, had a higher logistic EuroSCORE and lower pre
      procedural eGFR values compared with those who underwent SAVR (P < 0.0001 for
      all). The incidence of AKI was lower (P = 0.001; P = 0.014 after propensity score
      adjustment) in CKD patients who underwent TAVI (9.2%, need for haemodialysis:
      2.5%) compared with those who underwent SAVR (25.9%, need for haemodialysis:
      8.7%). CONCLUSION: Acute kidney injury occurred in 11.7% of the patients
      following TAVI and was associated with a greater than four-fold increase in the
      risk of postoperative mortality. Hypertension, chronic obstructive pulmonary
      disease, and blood transfusion were predictive factors of AKI. In those patients
      with pre-procedural CKD, TAVI was associated with a significant reduction of AKI
      compared with SAVR.

PMID- 20037181
TI  - Long-term prognosis of patients with peripheral arterial disease with or without
      polyvascular atherosclerotic disease.
AB  - AIMS: Patients with peripheral atherosclerotic disease often have multiple
      affected vascular beds (AVB), however, data on long-term follow-up and medical
      therapy are scarce. We assessed the prevalence and prognostic implications of
      polyvascular disease on long-term outcome in symptomatic peripheral arterial
      disease (PAD) patients. METHODS AND RESULTS: Two thousand nine hundred and thirty
      three consecutive patients were screened prior to surgery for concomitant
      documented cerebrovascular disease and coronary artery disease. The number of AVB
      was determined. Cardiovascular medication as recommended by guidelines was noted
      at discharge. Single, two, and three AVB were detected in 1369 (46%), 1249 (43%),
      and 315 (11%) patients, respectively. During a median follow-up of 6 years, 1398
      (48%) patients died, of which 54% secondary to cardiovascular cause. After
      adjustment for baseline cardiac risk factors and discharge-medication, the
      presence of 2-AVB or 3-AVB was associated with all-cause mortality (HR 1.3 95% CI
      1.2-1.5; HR 1.8 95% CI 1.5-2.2) and cardiovascular mortality (HR 1.5 95% CI 1.2
      1.7; HR 2.0 95% CI 1.6-2.5) during long-term follow-up, respectively. Patients
      with 2- and 3-AVB received extended medical treatment compared with 1-AVB at the
      time of discharge. CONCLUSION: Polyvascular atherosclerotic disease in PAD
      patients is independently associated with an increased risk for all-cause and
      cardiovascular mortality during long-term follow-up.

PMID- 20037182
TI  - Prevalence and risk factors of chronic kidney disease in the Thai adult
      population: Thai SEEK study.
AB  - BACKGROUND: Previous reports of chronic kidney disease (CKD) prevalence in
      Thailand varied from 4.3% to 13.8%. However, there were methodological concerns
      with these reports in terms of generalization and the accuracy of estimation.
      This study was, therefore, conducted to determine CKD prevalence and its risk
      factors in Thai adult populations. METHODS: The population-based Thai Screening
      and Early Evaluation of Kidney Disease (SEEK) study was conducted with cross
      sectional stratified-cluster sampling. Serum creatinine was analysed using the
      modified Jaffe method and then standardized with isotope dilution mass
      spectrometry. RESULTS: The study included 3,459 subjects were included in the
      study. The mean age was 45.2 years (SE = 0.8), and 54.5% were female. Six hundred
      and twenty-six subjects were identified as having CKD, which evidenced an overall
      CKD prevalence of 17.5% [95% confidence interval (95% CI) = 14.6-20.4%]. The CKD
      prevalence of Stages I, II, III and IV were 3.3% (95% CI = 2.5%, 4.1%), 5.6% (95%
      CI = 4.2%, 7.0%), 7.5% (95% CI = 6.2%, 8.8%) and 1.1% (95% CI = 0.7%, 1.5%),
      respectively. The prevalence of CKD was higher in Bangkok, the Northern and
      Northeastern regions than in the Central and Southern regions. Seven factors
      (i.e. age, gender, diabetes, hypertension, hyperuricaemia, history of kidney
      stones and the use of traditional medicines) were associated with CKD. Only 1.9%
      of the subjects were aware that they had CKD. CONCLUSIONS: CKD prevalence in the
      Thai population is much higher than previously known and published. Early stages
      of CKD seem to be as common as later stages. However, albuminuria measurement was
      not confirmed and adjusting for persistent positive rates resulted in the
      prevalence of 14.4%. Furthermore, the awareness of CKD was quite low in the Thai
      population.

PMID- 20037183
TI  - Cerebral microbleeds in predialysis patients with chronic kidney disease.
AB  - BACKGROUND: Gradient-echo T2*-weighted magnetic resonance imaging (T2*-weighted
      MRI) is highly sensitive for detecting cerebral microbleeds (CMBs). CMBs have
      been reported to be a risk factor for future cerebrovascular events and a marker
      of cerebral small vessel disease in the general population. Chronic kidney
      disease (CKD) is an independent risk factor for cardiovascular disease. The
      relationship between CKD and CMBs, which has not been clarified to date, is
      examined. METHODS: In this cross-sectional study, T2*-weighted MRI of brain was
      performed with a 1.5-T MRI system in 162 CKD patients (CKD stages 1-5, excluding
      CKD stage 5(D)) and 24 normal subjects. RESULTS: CMBs were found in 35 CKD
      patients (25.6%), but not in control subjects. CMBs were more prevalent in male
      patients, in those with higher blood pressure, advanced age and poor kidney
      function. There was a significant association between the prevalence of CMBs and
      the CKD stage, with higher prevalence of CMBs as the CKD stages advanced (P <
      0.01). Estimated glomerular filtration rate was a significant factor associated
      with the prevalence of CMBs, independent of age, gender and hypertension. There
      was no significant relationship between CMBs and the presence of diabetes
      mellitus and dyslipidemia. CONCLUSIONS: Decreased renal function is a significant
      risk factor for CMBs, independent of the presence of hypertension. Poor kidney
      function could be associated with future cerebrovascular events.

PMID- 20037184
TI  - Membranous nephropathy remains the commonest primary cause of nephrotic syndrome
      in a northern European Caucasian population.

PMID- 20037185
TI  - Performance evaluation of a particle-enhanced turbidimetric cystatin C assay
      using the Abbott Aeroset analyser and assessment of cystatin C-based equations
      for estimating glomerular filtration rate in chronic kidney disease.
AB  - INTRODUCTION: Measurement of glomerular filtration rate (GFR) is critical for the
      diagnosis and stratification of chronic kidney disease (CKD). Recent studies have
      shown that cystatin C is superior to creatinine for the detection of impaired
      GFR, and several cystatin C-based equations for estimating GFR have been
      developed for this clinical application. We conducted the present study to assess
      the applicability of cystatin C as a routine clinical laboratory index and to
      determine the performance of cystatin C-based equations in estimating GFR in CKD
      patients in China. METHODS: Performance evaluation of particle-enhanced
      turbidimetric cystatin C assay on the Abbott Aeroset analyser was carried out
      according to the National Committee for Clinical Laboratory document EP10-A2.
      Estimated GFR, which was generated from cystatin C-based equations, was compared
      with measured GFR, which was detected by plasma clearance of 99mTc-DTPA. RESULTS:
      Our cystatin C assay showed a very low total imprecision and linearity drift. All
      eight cystatin C-based GFR estimating equations underestimated or overestimated
      GFR as compared with GFR determined by 99mTc-DTPA clearance. CONCLUSION: Although
      the cystatin C assay is acceptable for routine clinical laboratory monitoring,
      none of the existing cystatin C-based equations were ideal for estimating GFR in
      Chinese CKD patients.

PMID- 20037186
TI  - Architectural and functional remodeling of cardiac and skeletal muscle cells in
      mice lacking specific isoenzymes of creatine kinase.
AB  - Muscle is the major consumer of fuels and ATP in the body. Mitochondria and
      glycolytic complexes serve as the main energy production locations, while the
      highest energy demands are associated with the sarcoplasmic reticulum,
      myofibrillar compartments and plasma membrane. Creatine kinase (CK) is a dimeric
      protein, which is deeply involved in the production of high energy storage
      compounds. This enzyme reversibly phosphorylates creatine (Cr) to phosphocreatine
      (PCr), and it is also highly adapted to specialized muscle function. To date,
      four major isoenzymes of CK have been identified, two of which occur in the
      cytosol and two in mitochondria. Disruption of the phosphotransfer system induced
      by an absence of either the sarcomeric mitochondrial CK or cytosolic CK or both
      isoenzymes of CK (CK(-/-)) in muscle cells leads to morphological and functional
      adaptations towards preservation of muscle contractile abilities. Remodeling of
      the cell ultrastructure observed in CK(-/-) cardiomyocytes and glycolytic fibers
      was associated with direct transfer of energy from places of energy production to
      locations of energy utilization. This direct interaction among the organelles can
      maintain a high ATP/ADP ratio near the cellular ATPases when CK is not
      functionally active. This review summarizes the function and role of CK across
      different muscle cells in knockout mice.

PMID- 20037187
TI  - Effect of 7-nitroindazole on the expression of intracellular calcium channels in
      the kidney of spontaneously hypertensive rats.
AB  - The spontaneously hypertensive rats (SHR) were fed with nitric oxide synthase
      (NOS) blocker 7-nitroindazole (7-NI, 10 mg/kg/day) for 6 weeks and an expression
      of intracellular calcium channels, SERCA and proapoptotic agents was evaluated in
      kidney. Treatment of rats with 7-NI resulted in a significant increase in mRNA
      and protein levels of the IP3 receptors type 1 and type 2, while mRNA levels of
      the IP3 receptor type 3 remained unchanged. The mRNA of other intracellular
      calcium channels, ryanodine receptors type 1 and type 2 was also upregulated by 7
      NI treatment. Gene expression of the SERCA2a, calcium pump responsible for
      loading intracellular stores with calcium, revealed increased gene expression due
      to 7-NI as well. Interestingly, proapoptotic agents caspase 3 and Bax were also
      upregulated by the 7-NI treatment. These results may indicate that nNOS blocker 7
      NI modifies intracellular calcium transport system, which may have impact on
      altered calcium handling and regulation of various metabolic pathways.

PMID- 20037188
TI  - D-pinitol attenuates the impaired activities of hepatic key enzymes in
      carbohydrate metabolism of streptozotocin-induced diabetic rats.
AB  - During diabetes mellitus, endogenous hepatic glucose production is increased as a
      result of impaired activities of the key enzymes of carbohydrate metabolism,
      which leads to the condition known as hyperglycemia. D-pinitol, a bioactive
      constituent isolated from soybeans, has been shown to reduce hyperglycemia in
      experimental diabetes. We therefore designed this study to investigate the effect
      of oral administration of D-pinitol (50 mg/kg b. w. for 30 days) on the
      activities of key enzymes in carbohydrate and glycogen metabolism in the liver
      tissues of streptozotocin-induced diabetic rats. The efficacy was compared with
      glyclazide, a standard hypoglycemic drug. Oral administration of D-pinitol to
      diabetic group of rats showed a marked decrease in the levels of blood glucose,
      glycosylated hemoglobin and an increase in plasma insulin and body weight. The
      activities of the hepatic enzymes such as hexokinase, pyruvate kinase, glucose-6
      phosphate dehydrogenase, glycogen synthase and hepatic glycogen content were
      significantly (p < 0.05) increased whereas the activities of glucose-6
      phosphatase, fructose-1,6-bisphosphatase, lactate dehydrogenase and glycogen
      phosphorylase were significantly (p < 0.05) decreased in diabetic rats treated
      with D-pinitol. The results suggest that alterations in the activities of key
      metabolic enzymes of carbohydrate metabolism could be one of the biochemical
      rationale by which D-pinitol attenuates the hyperglycemic effect in diabetic
      rats.

PMID- 20037189
TI  - Effect of L-carnitine on postischemic inhibition of protein synthesis in the rat
      brain.
AB  - The purpose of this study was to investigate effects of carnitine administration
      on protein synthesis recovery after transient cerebral ischemia. Rats received L
      carnitine in two doses of 16 mmol/kg i.p. 15 min before ischemia and just on the
      onset of reperfusion. Transient forebrain ischemia was induced by 4-vessel
      occlusion for 15 min, followed by 30 min or 7 days of reperfusion. Protein
      synthesis rate, reinitiation ability and neurodegeneration in the frontal cortex
      and hippocampus were measured by the incorporation of radioactively labelled
      leucine into polypeptide chains in postmitochondrial supernatants and by Fluoro
      Jade B staining. A protective effect was observed, on protein synthesis as well
      as the number of surviving neurons, in the L-carnitine-treated groups. Our
      results indicate that L-carnitine can exert a protective effect in the
      development of reperfusion-induced injury. L-carnitine significantly reduced the
      ischemia/reperfusion-induced inhibition of translation and neurodegeneration in
      the neocortex as well as in the highly sensitive hippocampus and dorsolateral
      striatum. We expect that the ability of L-carnitine to keep translational
      machinery on facilitates efficacy of postischemic remodulation of gene
      expression.

PMID- 20037190
TI  - Haloperidol moderately inhibits cardiovascular L-type calcium current.
AB  - Effects of haloperidol on L-type CaV1.2 channel were studied. Calcium current was
      measured in whole cell patch-clamp using calcium as a charge carrier. Inhibition
      by haloperidol was investigated in CaV1.2 channel natively expressed in rat
      cardiac myocytes and recombinant cardiac (CaV1.2a) and vascular (CaV1.2b) splice
      variants of the channel expressed in HEK 293 cells. Haloperidol inhibited L-type
      calcium current in a concentration-dependent manner with a threshold of 1 nmol/l.
      1 micromol/l haloperidol inhibited 20.6 +/- 3.6% of calcium current amplitude in
      cardiomyocytes, 25.4 +/- 2.6% of current amplitude through the CaV1.2b channel
      and 28.0 +/- 2.7% of current through the CaV1.2a channel. Inhibition was not
      accompanied by alteration of current waveform or by shift of current-voltage
      relation. In a current clamp haloperidol suppressed action potential generation.
      1 micromol/l of the drug shortened the action potential duration in part of the
      cells and suppressed fully action potential in other cells. Moderate inhibition
      of the L-type calcium channels by haloperidol might cause shortening of action
      potential. Complete abolishment of action potential must have been mediated by
      inhibition of another, likely sodium channel.

PMID- 20037191
TI  - Effects of static magnetic field exposure on antioxidative enzymes activity and
      DNA in rat brain.
AB  - The present study was undertaken in order to investigate the effects of static
      magnetic field (SMF) exposure on the antioxidative enzymes activity,
      malondialdehyde (MDA) concentration and DNA oxidation in male rat brain. The
      exposure of rats to SMF (128 mT, 1 h/day during 30 consecutive days) decreased
      the glutathione peroxidase (GPx; -39%, p < 0.05), CuZn superoxide dismutase (CuZn
      SOD; -35%, p < 0.05) and catalase (-59%, p < 0.05) activities in frontal cortex.
      The same treatment decreased the CuZn-SOD (-51%, p < 0.05) and Mn-SOD (-13%, p <
      0.05) activities in hippocampus. However, the glutathione levels remained
      unchanged in the both brain structures. In the hippocampus, SMF exposure
      increased MDA concentration (+32%, p < 0.05). Interestingly, exposed-rats to SMF
      displayed a significant increase of metallothioneins level in frontal cortex
      (+100%, p < 0.05), while the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo)
      concentration remained unaffected, indicating the absence of DNA oxidation. Our
      results indicated that sub-chronic exposure to SMF induced oxidative stress in
      rat hippocampus and frontal cortex. Metallothionein induction protected probably
      DNA against oxidative damage.

PMID- 20037192
TI  - Dietary supplementation with arachidonic acid but not eicosapentaenoic or
      docosahexaenoic acids alter lipids metabolism in C57BL/6J mice.
AB  - In order to investigate the effects of dietary supplementation rich in omega 3
      and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male
      mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty
      acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted
      for 1 month, food consumption of ND and n-3 PUFA were similar while it decreased
      in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and
      phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA
      while increased in n-6 PUFA fed mice comparing to control group. On the other
      hand, there was no difference between treatments in HDL and glucose levels.
      Expression of leptin (ob) gene transcripts in epididymal fat were significantly
      elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic
      ob receptor A (obRa) mRNA did not changed in response to diet regimes.
      Transmission and scanning electron microscopy showed different degrees in fatty
      changes in the liver of both PUFA groups including lipid droplet infiltration and
      Ito cells with over accumulated lipids. In conclusion, under PUFA dietary
      supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA
      but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups
      and/or different endocrine involvement. Moreover, the coincidently structural
      changes observed in liver of this group direct us to call for further studies to
      investigate the anti-obesity effect and safety of these PUFA under high
      supplementation condition.

PMID- 20037193
TI  - Temporal analysis of electroretinographic responses in fishes with rod-dominated
      and mixed rod-cone retina.
AB  - Photoreceptor content of fish retinas could be accessed by comparative
      electroretinographic (ERG) studies using flickering light stimuli that could
      separate rod-mediated vision where critical flicker frequency (CFF, frequency
      when the eye loses its ability to resolve individual light pulses) is usually
      less than 15 Hz from cone-mediated vision. Four fish species inhabiting different
      photic environments (small-spotted dogfish shark--Scyliorhinus canicula, eel-
      Anguilla anguilla, painted comber--Serranus scriba, Prussian carp--Carassius
      gibelio) were investigated. Dogfish shark b-wave amplitudes significantly
      decreased at low frequency of stimulation and CFF was reached at 3.2 Hz. A
      similar effect on the b-wave amplitude was observed in the eel, but CFF occurred
      at around 20 Hz. Conversely, b-waves of painted comber and Prussian carp remained
      unaltered under intermittent low-frequency stimulation, and CFFs were around 25
      and 30 Hz, respectively. Additional support in accessing the receptor content of
      fish retinas was given by the characterization of the OFF-response (d-wave) after
      light adaptation. Monotonous time course of the b-wave dark adaptation indicated
      a rod dominated retina of the dogfish shark. Observed results indicate that the
      dogfish shark possesses preponderantly rod retina, that of the eel is rod
      dominated, while Prussian carp and painted comber have cone-rich retinae.

PMID- 20037194
TI  - Fluorescence approach to evaluating conformational changes upon binding of beta
      spectrin ankyrin-binding domain mutants with the lipid bilayer.
AB  - The major component of the cell membrane skeleton, spectrin, is anchored in the
      cell membrane via interactions with membrane proteins. It has been previously
      shown that both erythroid and non-erythroid spectrin interact directly with
      membrane phospholipids (mainly aminophospholipids). One of the binding sites
      responsible for these interactions is located in the ankyrin-binding domain. In
      the present study, in order to better understand the character of binding, a more
      detailed investigation of the interactions between the beta-spectrin fragments
      corresponding to the truncated mutants of the ankyrin-binding domain (Frag1 and
      Frag3) and liposomes of different compositions were carried out. The obtained
      results suggest that the binding of both spectrin fragments with liposomes
      induces conformational changes within the protein. Analysis of the changes in
      intrinsic tryptophan fluorescence spectra upon binding with liposomes, together
      with quenching studies (from the water and membrane hydrocarbon environment),
      allows for qualitative description of changes in proteins conformation. Our
      results suggest that the largest conformational changes occur for Frag1 bound to
      PC : PE (2 : 3) liposomes what is consistent with previous studies on monolayers.
      They are also in good agreement with those obtained previously for native
      erythroid and nonerythroid spectrin molecules.

PMID- 20037195
TI  - Modulation of cell proliferation and differentiation of human lung carcinoma
      cells by the interferon-alpha.
AB  - Treatments of non-small cell lung cancer (NSCLC), the most common form of lung
      cancer, still remain poor. Interferon alpha (IFN-alpha), an important
      physiological immunomodulator, possesses direct cytotoxic and cytostatic effects
      on tumour cells, antiangiogenic effects, and activates anti-tumour immunity.
      Recently, the IFN-alpha oncologic indications have included melanoma, renal
      carcinoma, and different types of leukaemia. However, the application of IFN
      alpha in therapy of lung cancer has not been validated yet. Herein the human lung
      carcinoma cell line A549, a model of NSCLC in vitro, was used to pursue the
      effect of IFN-alpha on A549 cell proliferation and differentiation together with
      the effect on protein expression and activity of three ATP-transporters mediating
      multi-drug resistance (MDR). IFN-alpha significantly inhibited the proliferation
      of A549 cells which was not connected with arrest in a particular cell cycle
      phase. Further, IFN-alpha-mediated differentiation of A549 was observed based on
      an increase in alkaline phosphatase activity. Simultaneously, IFN-alpha increased
      the expression and activity of ATP-transporters mediating MDR. Thus, the IFN
      alpha down-regulation of NSCLC cell proliferation was accompanied by a potential
      of cells to exclude potential therapeutic substances such as chemotherapeutic
      agents. These effects could have a significant impact on considerations of IFN
      alpha as a therapeutic agent for NSCLC.

PMID- 20037196
TI  - Influence of decavanadate on rat synaptic plasma membrane ATPases activity.
AB  - The in vitro influence of decameric vanadate species on Na+/K+-ATPase, plasma
      membrane Ca2+-ATPase (PMCA)-calcium pump and ecto-ATPase activity, using rat
      synaptic plasma membrane (SPM) as model system was investigated, whereas the
      commercial porcine cerebral cortex Na+/K+-ATPase served as a reference. The
      thermal behaviour of the synthesized decavanadate (V10) has been studied by
      differential scanning calorimetry and thermogravimetric analysis, while the type
      of polyvanadate anion was identified using the IR spectroscopy. The concentration
      dependent responses to V10 of all enzymes were obtained. The half-maximum
      inhibitory concentration (IC50) of the enzyme activity was achieved at (4.74 +/-
      1.15) x 10(-7) mol/l for SPM Na+/K+-ATPase, (1.30 +/- 0.10) x 10(-6) mol/l for
      commercial Na+/K+-ATPase and (3.13 +/- 1.70) x 10(-8) mol/l for Ca2+-ATPase,
      while ecto-ATPase is significantly less sensitive toward V10 (IC50 = (1.05 +/-
      0.10) x 10(-4) mol/l) than investigated P-type ATPases. Kinetic analysis showed
      that V10 inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity and
      apparent affinity for ATP (increasing K(m) value), implying a mixed mode of
      interaction between V10 and P-type ATPases.

PMID- 20037197
TI  - Transepithelial transport of ambroxol hydrochloride across human intestinal Caco
      2 cell monolayers.
AB  - This study aimed i) to characterize the transepithelial transport of the
      mucolytic agent ambroxol hydrochloride across the intestinal barrier, ii) to
      classify the ambroxol according to Biopharmaceutics Classification System (BCS)
      and iii) to predict ambroxol absorption in humans. Transport of ambroxol (100,
      300 and 1000 micromol/l) was studied in a human colon carcinoma cell line Caco-2
      in apical to basolateral and basolateral to apical direction, under iso-pH 7.4
      and pH-gradient (6 vs. 7.4) conditions. The relative contribution of the
      paracellular route was estimated using Ca2+-free transport medium. Ambroxol
      samples from receiver compartments were analysed by HPLC with UV detection (242
      nm). Results showed that ambroxol transport is linear with time, pH-dependent and
      direction-independent, displays non-saturable (first-order) kinetics. Thus, the
      transport seems to be transcellular mediated by passive diffusion. Estimated high
      solubility and high permeability (P(app) = 45 x 10(-6) cm/s) of ambroxol rank it
      among well absorbed compounds and class I of BCS. It can be expected that the
      oral dose fraction of ambroxol absorbed in human intestine is high.

PMID- 20037198
TI  - Activation of MAPKs influences the expression of drug-metabolizing enzymes in
      primary human hepatocytes.
AB  - We examined the effects of model activators of mitogen-activated protein kinases
      (MAPKs) on basal and rifampicin-, phenobarbital- and dioxin-inducible expression
      of phase I and phase II biotransformation enzymes in primary human hepatocytes.
      Cells were treated for 24 h with sorbitol (SOR), anisomycin (ANI) and epidermal
      growth factor (EGF) in the presence or absence of inducers. The levels of CYP1A1,
      CYP1A2, CYP2B6, CYP3A4, UGT1A1, UGT2B17, SULT1A1, SULT2A1, SULT1B2, GSTA1, GSTA2
      mRNAs were determined. SOR and EGF inhibited the expression of the tested genes,
      while ANI had no effect. We conclude that MAPKs play important role in the
      transcriptional regulation of drug-metabolizing enzymes.

PMID- 20037199
TI  - Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal
      carcinoma in a sample of Egyptian individuals.
AB  - The study was planned as a pilot study to investigate two common polymorphisms in
      the MTHFR gene c.677C > T and c.1298A > C and their association with enhanced
      risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood
      samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens
      from colonic and rectal carcinoma tissues in addition to cancer free tissues were
      obtained from all cases. Frequencies of MTHFR677T and 1298C alleles were
      significantly higher among cases of CRC tumor tissues (50% and 56%, respectively)
      than germ line alleles in CRC patients (33% and 41%, respectively) and healthy
      controls (21% and 35%, respectively). Frequencies of heterozygous and homoyzgous
      polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always
      the highest. At position 677, TT and CT genotype frequencies were 17% and 66%
      with an odds ratio {OR} of 11 [95% confidence interval {CI} 2.39-50.59] and OR
      8.34 [95%CI 2.97-23.92], respectively, in carcinoma tissues. While in the germ
      line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR
      1.57 [95%CI 0.26-9.51] and 2.99 [95%CI 1.25-7.12], respectively, compared to
      controls (6% and 29%, respectively). The combined genotype MTHFR 1298CC + AC
      frequencies were 86% with OR 3.71 [95%CI 1.28-10.78] in carcinoma tissues, 69%
      with OR 1.35 [95%CI 0.57-3.21] in germ line of patients and 62% in controls. The
      combined genotype 677CT plus any of the following genotypes 1298AA, AC or CC
      enhanced risk of CRC, when comparing germ line DNA polymorphism of patients
      versus peripheral blood DNA of control subjects with OR 4.5 [95%CI 0.94-21.56],
      OR 3.12 [95%CI 0.79-12.36] and OR 18 [95%CI 1.56-207.5], respectively, suggesting
      strong genetic predisposition of certain Egyptian population to CRC. These
      results suggested that at least one C to T polymorphism at 677MTHFR gene is
      required to significantly increase the risk for CRC development. Further large
      scale studies are required to confirm the present findings.

PMID- 20037200
TI  - Diagnostic potential in prostate cancer of a panel of urinary molecular tumor
      markers.
AB  - Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease.
      Therefore, the search for a combination of assays using a panel of tumor markers
      is fundamental for a more precise and reliable diagnosis. In the present study we
      investigated the diagnostic value of five different genes, associated with PCa
      carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine
      protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-alpha-D-galatosamine
      transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients,
      with previously untreated, histologically verified PCa and forty-six patients
      with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute
      concentration of the transcript levels of each gene was calculated by
      quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa
      or BPH after prostatic massage. The diagnostic value of a concomitant examination
      of these markers was evaluated by logistic regression analysis. We demonstrated
      that the diagnostic potential of the combined urinary PSA and PSMA level was
      significantly better than that of each singularly considered marker, including
      total serum PSA, the present gold standard test for PCa diagnosis.

PMID- 20037201
TI  - Oxidant-antioxidant status in Indian patients with carcinoma of posterior one
      third of tongue.
AB  - OBJECTIVE: Cancer of posterior one-third of tongue is seen in 0.43% of total
      world population. Worldwide, cancer of tongue constitutes 5% of the total cancer
      incidence. Squamous cell cancer of head and neck is the most common cancer
      encountered in India. Oxidative stress is potentially harmful to cells and ROS
      are involved in multistage carcinogenesis, in initiation and promotion. Moreover,
      the extent of ROS-induced oxidative damage can be exacerbated by decreased
      efficiency of antioxidant defense mechanisms. The aim of this study was to assess
      the alterations in the circulating lipid peroxide, antioxidant components and the
      activities of defense enzymes in patients with cancer of posterior one-third of
      tongue, with respect to healthy controls in the Indian population. METHODS: 60
      patients with newly diagnosed, histologically proven cases of locally advanced
      squamous cell carcinoma (Stage III-IVa) of posterior one-third of tongue were
      recruited into the study. 60 healthy controls, without history or laboratory
      evidence of malignancy and inflammatory disorder, were also included in the
      study, after obtaining informed consent. Single blood samples were taken from
      patients, before start of therapy and controls. Lipid peroxides, conjugated
      dienes, reduced glutathione (GSH), vitamin C and E were estimated using standard
      methods. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assayed
      using commercially available kits from Randox, UK. RESULTS: The pre-treatment
      levels of plasma lipid peroxide and conjugated dienes were significantly elevated
      in patients with carcinoma of posterior one-third of tongue, as compared with
      controls (p=0.001). Significantly lowered levels of GSH, GPx, SOD and antioxidant
      vitamins were observed in cancer patients, when compared to control subjects
      (p=0.001). Pearson's correlation analysis showed a highly statistitically
      significant negative correlation between pro-oxidant and anti-oxidant levels in
      patients. CONCLUSION: Increased levels of oxidative stress markers and decreased
      levels of antioxidants in carcinoma of posterior one-third of tongue suggest that
      oxidative stress markers play a significant role in the pathophysiology of tongue
      cancer. These findings may suggest possible use of antioxidant supplementation as
      prophylactic agents for prevention and treatment of tongue cancer. A larger
      patient cohort for therapeutic response after treatment with a longer follow-up
      period studies might yield more significant data on their probable use as
      predictors of chemoradiosensitivity of cancer of tongue.

PMID- 20037202
TI  - Cytotoxic studies of anti-neoplastic drugs on human lymphocytes--in vitro
      studies.
AB  - All the anti-cancer drugs proved to be highly cytotoxic agents to normal cells
      like lymphocyte cells used in our study which do not come under rapidly dividing
      cells like bone marrow cells, fetal cells, germ cells, hair follicle cells,
      intestinal cells, etc. but will proliferate when maintained in growth media with
      proliferation agents. In this investigation, we determined the effect of anti
      cancer drugs on lymphocyte cultures from peripheral blood of healthy non-smoking
      donors under in vitro conditions by employing MTT assay. All the experiments were
      carried out with seven anti-cancer drugs; Carboplatin, Avastin, Vinorelbine,
      Tamoxifen Citrate, Methotrexate, Gemcitabine and Paclitaxel which are broad
      spectrum cancer drugs and being used in six different types of chemotherapy in
      cancers. We have documented the results that were evaluated by statistical
      analysis. The MTT assay is now widely adopted by researchers and industry, as it
      is a rapid spectrophotometric method for determining cell viability in cell lines
      and in vitro. The initial or dose-finding studies determine the drug toxicity
      relative to dose and subsequent studies define the spectrum of activity of the
      drug. And moreover, no anti-neoplastic drug is devoid of side effects. Hence,
      this investigation determines the lethal concentrations and thereby the dosages
      at which individual anti-neoplastic drugs and also combinations can bring about
      certain degree of cytotoxicity in human lymphocytes which with comparative study
      on cancer cell lines would be useful in defining drug dosages.

PMID- 20037203
TI  - Ethnic variability of HIF-1alpha polymorphisms.
AB  - The hypoxia-inducible factor -1alpha (HIF-1alpha) is a transcription factor that
      plays a crucial role in the cellular response to hypoxia. The C1772T (P582S) and
      G1790A (A588T) polymorphisms, within the oxygen dependent degradation domain of
      HIF-1alpha protein, seem to be important in the oxygen regulation of protein
      stability, influencing the progression of some hypoxic solid tumors. Despite the
      numerous reports about the influence of these single-nucleotide polymorphisms
      (SNPs) on cancer incidence and progression, there are no published data
      concerning the interethnic variability of these polymorphisms. Here we
      investigated the SNPs C1772T and G1790A, in four distinct populations from
      Portugal, Mozambique, Colombia and Guinea-Bissau. The allelic frequency of the
      1772T allele was 0.122 in Portugal, 0.151 in Colombia, 0.246 in Mozambique and
      0.08 in Guinea-Bissau. Statistically significant differences were observed when
      comparing the Portuguese population with the Mozambican one (p=0.020) and the
      populations from Mozambique and Guinea-Bissau (p< 0.0001). The Mozambican
      population had an allelic frequency of 0.006 for the 1790A allele, which was not
      detected among the other studied populations. In conclusion, there is an
      ethnicity-related variation in the frequency of C1772T and G1790A polymorphisms
      of the HIF-1alpha gene that may be relevant in the context of tumor
      aggressiveness and progression.

PMID- 20037204
TI  - Human kallikrein related peptidases 6 and 13 in combination withCA125 is a more
      sensitive test for ovarian cancer than CA125 alone.
AB  - The current biomarker for ovarian cancer, CA125, lacks the sensitivity and
      specificity required to detect early stage ovarian cancers. Since several
      Kallikreins (KLKs) are up regulated in ovarian cancer, they represent a potential
      pool of biomarkers for ovarian cancer. The purpose of this study is to determine
      if elevated expression levels of Muc16 (CA125 gene), KLK6 and KLK13 represent a
      more sensitive test for detection of early stage ovarian cancer than Muc16 alone.
      Using quantitative real-time PCR, 106 sporadic ovarian tumors and 8 normal
      ovaries were evaluated for mRNA expression. Analysis for increased expression
      levels, above controls, of either KLK6, KLK13 or Muc16 improved overall
      sensitivity to 93%, from 82% for Muc16 alone. Likewise, the negative predictive
      value increased from 27% to 50% (Muc16 alone compared to combined). With early
      stage cancers (n=32), both sensitivity increased 50-56% (individually) to 72%
      (combined), and negative predictive value increased (30% Muc16 to 58% combined).
      These results show a combined panel of KLK6, KLK13, and Muc16, is a more
      sensitive test to detect early stage ovarian cancer than Muc16 alone, indicating
      assaying for several kallikrein-related peptidases, in addition to CA125, could
      provide a significant advantage to detect ovarian cancer in the early stages.

PMID- 20037205
TI  - Racial differences in serum cotinine levels of smokers.
AB  - The purpose of this study was to estimate black/white differences in cotinine
      levels for current smokers of both sexes, and to explore the potential
      contribution of mentholated cigarettes to these differences. Sera from 255
      current smokers sampled from Southern Community Cohort Study participants (65
      black men, 65 black women, 63 white men, 62 white women) were analyzed for
      cotinine, and linear regression was used to model the effect of race on cotinine
      level, adjusting for the number of cigarettes smoked within the last 24 hours,
      use of menthol vs. non-menthol cigarettes, exposure to environmental tobacco
      smoke, and age. Black smokers smoked fewer cigarettes than white smokers, yet had
      crude mean cotinine levels nearly as high or higher than white smokers. After
      multivariate adjustment, cotinine levels were an average of 50 ng/ml higher among
      black than white women (p=0.008) and non-significantly 12 ng/ml higher among
      black than white men (p=0.52). We observed no increase in cotinine levels
      associated with menthol cigarette use. We conclude that differences in cotinine
      levels among smokers suggest racial variation in exposure to and/or metabolism of
      tobacco smoke constituents, but our findings do not support a role for menthol
      preference in this disparity.

PMID- 20037206
TI  - Genetic association of DLG5 R30Q with familial and sporadic inflammatory bowel
      disease in men.
AB  - BACKGROUND: The association of DLG5 R30Q with IBD has been replicated in several
      populations, but is not statistically significant in others. We studied the
      incidence of DLG5 alleles in a population of IBD patients from Pennsylvania.
      METHODS: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR
      based RFLP methods in a total of 521 subjects, that included 105 individuals with
      IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and
      170 unrelated healthy controls. R30Q was further analyzed with SNPlex Genotyping
      System in 473 samples. RESULTS: RFLP genotyping data showed that, DLG5 R30Q was
      significantly associated with IBD overall (p=0.006), and separately with CD
      (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to
      a male-associated effect (male vs female p=0.015 vs 0.241 (IBD), p=0.024 vs 0.190
      (CD), and p=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was
      elevated in both affected and unaffected members in the familial IBD cohort
      compared to healthy controls (p=0.037). In the family pedigrees, we observed
      differences in the expression of IBD in individuals carrying the A allele between
      families. CONCLUSIONS: In the studied population, DLG5 R30Q was associated with
      all forms of IBD. An elevated presence of the R30Q variant was observed in all
      members of a familial IBD registry. This association of the R30Q variant with IBD
      was male-specific.

PMID- 20037207
TI  - Association of single nucleotide polymorphisms in CYP1B1 and COMT genes with
      breast cancer susceptibility in Indian women.
AB  - Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes play
      critical roles in estrogen metabolism. Alterations in the catalytic activity of
      CYP1B1 and COMT enzymes have been found associated with altered breast cancer
      risk in postmenopausal women in many populations. The substitution of leucine
      (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1,
      however, substitution of Val to methionine (Met) at codon 158 decreases the
      catalytic activity of COMT. The present study was performed to evaluate the
      associations of CYP1B1 Leu(432)Val and/or COMT Val(158)Met polymorphisms with
      total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT
      and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed
      employing polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not
      exhibit statistically significant association with breast cancer risks when
      analyzed individually, COMT wild type (Val(158)Val) in combination with CYP1B1
      heterozygous variant (Leu(432)Val) [OR: 0.21; 95% CI (0.05-0.82), p value; 0.021]
      and COMT heterozygous variant (Val(158)Met) in combination with CYP1B1 wild type
      (Leu(432)Leu) [OR: 0.29; 95% CI (0.08-0.96), p value; 0.042] showed significant
      protective association with premenopausal breast cancer risk. The results
      demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their
      inverse combination offer protection against breast cancer in premenopausal
      Indian women.

PMID- 20037208
TI  - Endothelin-converting enzyme-1 promoter polymorphisms and susceptibility to
      sporadic late-onset Alzheimer's disease in a Chinese population.
AB  - Endothelin converting enzyme (ECE-1) is a candidate Alzheimer disease
      susceptibility gene. It was previously reported that western individuals
      homozygous for the C-338A polymorphism (AA) within the ECE1 gene promoter region
      are at reduced risk of developing late onset Alzheimer disease (LOAD). A further
      polymorphism, T-839G, is present within the ECE1 promoter region but a potential
      association with LOAD has not been studied. We therefore studied possible
      associations between these ECE1 polymorphisms and LOAD in a Chinese population.
      Subjects comprised 376 Chinese LOAD patients and 376 age- and sex-matched
      controls; all subjects were typed for the ECE1 C-338A and the T-839G
      polymorphisms. We report that the frequency of the 338A allele was decreased in
      LOAD patients compared to controls (adjusted OR =0.73; 95% CI=0.54-0.98; P=0.03).
      There was no significant association between T-839G genotype and LOAD, however
      the combined 839T/338A haplotype was significantly associated with decreased risk
      of LOAD (OR=0.73; 95% CI=0.57-0.93; P=0.01). This study argues that the ECE1 338A
      allele is protective against LOAD in a Chinese population.

PMID- 20037209
TI  - Genetic factors associated with rheumatoid arthritis and systemic vasculitis:
      Evaluation of a panel of polymorphisms.
AB  - Immune and inflammatory response activation is a common feature of connective
      tissue diseases and systemic vasculitis. The aim of our study was to evaluate the
      possible involvement of TNFalpha c.-308A > G, IL-10 c.-1082A > G, uteroglobin
      c.38A > G, TGFbeta 1 c.869C > T and NFkappaB2 c.-1837T > C gene polymorphisms in
      susceptibility to connective tissue diseases. Our study cohort included 68
      unrelated patients affected by rheumatoid arthritis (RA) (37 patients) and ANCA
      positive [micropolyangiitis (mPA) 17 patients] or ANCA-negative systemic
      vasculitis [including 8 patients with Henoch-Schonlein purpura (HSP) and 6
      patients with mixed cryoglobulinaemia (MC)] as well as 98 control subjects.
      Allele frequency analysis of uteroglobin c.38G > A polymorphism showed a
      significant increase in the c.38A allele in patients (p= 0.002). Genotype
      frequency analysis of uteroglobin and NF-kappaB2 gene polymorphisms in patients
      showed an increase in c.38GA and c.38AA genotypes in the uteroglobin gene
      (p=0.02) coupled with an increase in homozygous c.-1837CC in the NF-kappaB2 gene
      (p=0.02). Our data suggest that genetic variation in UG and NF-kappaB2 pathways
      could have effects in connective tissue disease susceptibility.

PMID- 20037210
TI  - Apolipoprotein E genotypes in Mexican patients with Parkinson's disease.
AB  - BACKGROUND: The association of the apolipoprotein (Apo E) -epsilon4 allele to
      neurodegenerative diseases such as Parkinson's disease (PD) has been analyzed in
      several studies. This association has been identified by amyloid deposits and
      neurofibrillary tangles in the brains of patients with neurodegenerative
      diseases. METHOD: In this study the possible relationship between Apo E alleles
      and PD patients was analyzed in 105 patients with PD and 107 healthy controls
      from a Mexican population. RESULTS: Allele analysis in PD vs. controls was:
      epsilon2 in 6% and 2.3%, respectively; epsilon3 in 73% and 88.3%; and epsilon4}
      in 21% and 9.4%. The epsilon3 allele showed a protective risk effect with an Odds
      ratio (OR) of 0.36 (95%CI 0.20-0.61) and p < 0.05; contrary results were observed
      for the epsilon4 allele, which showed an increased risk for PD, with an OR of
      2.57(95% CI 1.42-4.79) and p < 0.05. Upon multivariate analysis showed PD risk
      was evident in patients who were carriers of the genotype epsilon3/epsilon4; age
      group (fifty or more years) and had exposure to pesticides and solvents (p <
      0.05). CONCLUSIONS: The epsilon3/epsilon3}; epsilon3/epsilon4 genotypes of the
      Apo E, were positively associated with sporadic PD.

PMID- 20037211
TI  - TPMT and DPD polymorphisms: Efficient screening method for Indian patients
      considering taking Thiopurine and 5-FU drugs.
AB  - INTRODUCTION: Development of DNA-based tests for TPMT/DPD polymorphisms can help
      clinicians and patients to make important decisions about cancer treatment. Also,
      due to lack of Indian data, we aimed at the development and validation of these
      tests in Indian patients. MATERIALS AND METHODS: Molecular assays were used for
      identifying TPMT/DPD variations; validated by DNA sequencing. RESULTS: Molecular
      assays have been used for screening TPMT*2, *3A, *3B, *3C alleles and IVS14+1(G-
      >A) in DPD gene. A patient, exhibiting neutropenia on 6-MP was observed to be
      G460A-homozygote, while, two Acute Lymphoblastic Leukemia (ALL) patients with
      side-effects exhibited wild-type alleles. Two patients showing 6-MP side-effects
      and responding well to the same drug at later stage also carried wild-type
      alleles. DISCUSSION: G460A homozygosity in a patient allowed clinicians to stop 6
      MP treatment, improving patient's health status. Two ALL patients showing side
      effects were wild-type, indicating presence of unidentified rare variations. Two
      patients with wild-type allele showed side-effects during 6-MP treatment, but
      responded well to same drug at later stage, suggesting side-effects to be
      attributable to multiple biological and environmental processes. Absence of
      IVS14+1(G-->A) in DPD gene will not exclude possibility of another mutation.
      CONCLUSION: Molecular assays for determining common TPMT/DPD variations, can
      provide accurate diagnosis and efficient therapies in future clinical studies.

PMID- 20037212
TI  - Molecular network analysis suggests aberrant CREB-mediated gene regulation in the
      Alzheimer disease hippocampus.
AB  - The pathogenesis of Alzheimer disease (AD) involves the complex interaction
      between genetic and environmental factors affecting multiple cellular pathways.
      Recent advances in systems biology provide a system-level understanding of AD by
      elucidating the genome-wide molecular interactions. By using KeyMolnet, a
      bioinformatics tool for analyzing molecular interactions on the curated
      knowledgebase, we characterized molecular network of 2,883 all stages of AD
      related genes (ADGs) and 559 incipient AD-related genes (IADGs) identified by
      global gene expression profiling of the hippocampal CA1 region of AD brains in
      terms of significant clinical and pathological correlations (Blalock et al., Proc
      Natl Acad Sci USA 101: 2173-2178, 2004). By the common upstream search, KeyMolnet
      identified cAMP-response element-binding protein (CREB) as the principal
      transcription factor exhibiting the most significant relevance to molecular
      networks of both ADGs and IADGs. The CREB-regulated transcriptional network
      included upregulated and downregulated sets of ADGs and IADGs, suggesting an
      involvement of generalized deregulation of the CREB signaling pathway in the
      pathophysiology of AD, beginning at the early stage of the disease. To verify the
      in silico observations in vivo, we conducted immunohistochemical studies of 11 AD
      and 13 age-matched control brains by using anti-phoshorylated CREB (pCREB)
      antibody. An abnormal accumulation of pCREB imunoreactivity was identified in
      granules of granulovacuolar degeneration (GVD) in the hippocampal neurons of AD
      brains. These observations suggest that aberrant CREB-mediated gene regulation
      serves as a molecular biomarker of AD-related pathological processes, and support
      the hypothesis that sequestration of pCREB in GVD granules is in part responsible
      for deregulation of CREB-mediated gene expression in AD hippocampus.

PMID- 20037214
TI  - Corticospinal tract injury in patients with diffuse axonal injury: a diffusion
      tensor imaging study.
AB  - Diffusion tensor imaging (DTI) can be useful in detecting corticospinal tract
      (CST) injury at the subcortical white matter level. In the current study, we
      attempted to investigate the incidence and distribution of CST injury in patients
      with diffuse axonal injury (DAI), using DTI. Fourteen patients who showed motor
      weakness without any specific lesion along the CST pathway on conventional brain
      MRI, and twelve age-matched, normal healthy control subjects were recruited. DTI
      was performed using 1.5 T with a synergy-L Sensitivity Encoding (SENSE) head
      coil. Fractional anisotropy was measured using the region of interest method. A
      CST injury was defined as the FA value of a certain area being decreased two
      standard deviations below that of normal controls. All 14 patients had more than
      one lesion at the CST injury, and the mean number of CST injuries was 3.6 (range:
      2-7). The CSTs were involved at the following locations: the pons (61%), the
      cerebral peduncle (39%), the corona radiata (21%), the medulla (14%), and the
      posterior limb (11%). The pons was the most prevalent area of CST injury in
      patients with weakness caused by DAI at the subcortical level. We found that DTI
      is a useful technique for detecting a DAI of the CST at the subcortical level.

PMID- 20037215
TI  - Assessing the reliability of the Modified Modified Ashworth Scale between two
      physiotherapists in adult patients with hemiplegia.
AB  - The Modified Modified Ashworth Scale (MMAS) is a simple clinical outcome measure
      to assess muscle spasticity in people with brain injury. The objective of this
      cross-sectional study was to assess the interrater reliability of the MMAS in the
      upper limb of adult patients with hemiplegia. Participants were fifteen patients
      with a mean age of 57.3 +/- 14.4 years. They had brain injury on average 33.3 +/-
      26.2 months earlier. Two common spastic muscle groups (elbow flexor and wrist
      flexor) on the hemiparetic side of the patients were rated by two
      physiotherapists according to a standardized protocol. The order of raters'
      assessment and the sequence of muscle testing was randomized. The weighted Kappa
      (kappaw) values were calculated for reliability. The kappaw was 0.61 for elbow
      flexor and 0.78 for wrist flexor. Results support the good interrater reliability
      of the MMAS for persons with upper limb spasticity.

PMID- 20037216
TI  - Effects of age, gender, and cognitive, functional and motor status on functional
      outcomes of stroke rehabilitation.
AB  - Our objective was to evaluate the relation between age, gender, initial
      functional, cognitive and motor condition, spasticity, diabetes mellitus, and
      functional outcome after rehabilitation of stroke patients. Eighty-eight patients
      who had suffered stroke were administered in this study. Participants were stroke
      patients undergoing rehabilitation in Istanbul Physical Treatment and
      Rehabilitation Training and Research Hospital. Functional condition (Functional
      Independence Measurement (FIM)), spasticity (Ashworth Scale), cognitive condition
      (Mini Mental State Evaluation (MMSE)), post-treatment FIM were measured. A
      significant positive association between MMSE at admission and the functional
      discharge measures was observed. A significant positive association Brunnstrom
      (upper lower extremity assessment) scores and the functional discharge measures
      was observed. A significant positive association between spasticity at admission
      and the functional discharge measures was observed. In conclusions, the admission
      functional, motor, cognition condition, age, spasticity were a significant
      predictors of total and motor FIM score at discharge, but not gender and diabetes
      mellitus.

PMID- 20037217
TI  - A case report on the use of a novel optokinetic chart stimulation intervention
      for the restoration of voluntary movement and mobility in a patient with an acute
      hemorrhagic stroke.
AB  - BACKGROUND AND PURPOSE: The objective of this case report is to report on the use
      of novel optokinetic chart stimulation to achieve recovery of affected upper limb
      and affected lower limb voluntary movements and full recovery of mobility in a
      patient with an acute hemorrhagic stroke. METHOD: An optokinetic chart was moved
      in front of the patient: from side to side, up and down and finally forwards and
      backwards. Specific active-assisted exercises of affected shoulder anti-gravity
      muscles were also carried out. These were external rotation, abduction, flexion
      and a combination of these through the D2F proprioceptive neuromuscular
      facilitation (PNF) pattern. RESULTS: Oxford score improved from 0/5 on admission
      to 3/5 on discharge, after 8 weeks, while Barthel Index improved from 0/20 to
      20/20. STREAM scores improved from 1/70 on admission to 18/70 a month after
      admission and 70 /70 at follow-up 3 months after discharge. DISCUSSION:
      Optokinetic chart stimulation led to restoration of voluntary movement on the
      affected side as well as restoration of independent mobility. Further research on
      the use of the optokinetic chart to enhance neural plasticity for restoration of
      voluntary movement and mobility is recommended.

PMID- 20037218
TI  - Cortical activation pattern of compensatory movement in stroke patients.
AB  - OBJECTIVE: Little is known about the cortical activation pattern of compensatory
      movement (CM) in stroke patients. We attempted to investigate the cortical
      activation pattern of compensatory movement in stroke patients, using functional
      MRI (fMRI). METHODS: Eight hemiparetic stroke patients were recruited for this
      study. We measured the shoulder abduction angle when each subject was simulating
      eating in a sitting position, which was considered as the degree of CM. The fMRI
      was performed at 1.5T using an elbow motor task at a frequency of 0.5 Hz.
      RESULTS: There was an inverse correlation between the shoulder abduction angle of
      the affected side and the LI (Laterality Index) (r=-0.745; p< 0.05). The shoulder
      abduction angle of the affected side was significantly related to the sum of
      activated voxels in all regions of interest (r=0.776; p< 0.05) and the activated
      voxels of the supplementary motor area (r=951; p< 0.05). However, we did not find
      any correlation between the shoulder abduction angle and the activated voxels of
      other brain areas. CONCLUSIONS: We demonstrated that a greater shoulder abduction
      angle on the affected side requires more cortical activation. Therefore, CM
      appears to be related to the change of the cortical motor control toward greater
      recruitment of cortical neurons.

PMID- 20037219
TI  - Body weight supported treadmill training at very low treatment frequency for a
      young adult with incomplete cervical spinal cord injury.
AB  - INTRODUCTION: Body weight supported treadmill training (BWSTT) using high
      treatment frequency has been shown to improve gait after spinal cord injury
      (SCI). This case report describes the use of BWSTT at a very low treatment
      frequency. SUBJECT: The subject was a 19 y.o. female with an incomplete C6 SCI,
      one year post-injury, with multiple gait deficits. INTERVENTION: BWSTT was
      combined with conventional rehabilitation. Mean treatment frequency was 1.16
      days/wk over 28.5 wks. A BWSTT progression algorithm based on observational gait
      analysis guided progressive changes in support levels, treadmill speed, and
      session length. OUTCOMES: During the first 3 sessions, the subject tolerated an
      average of 15.7 minutes of BWSTT with 26% BWS at 0.8 m/s, improving to an average
      of 28 minutes of BWSTT with 10% BWS at 1.6 m/s in the last 3 sessions. Following
      28.5 wks of very low frequency BWSTT, the subject displayed improved kinematics,
      walking speed, endurance, and distance during overground gait. CONCLUSION: Very
      low frequency BWSTT combined with conventional treatment improved quality and
      endurance of walking for a person with incomplete cervical SCI. Further work is
      needed to evaluate the long-term outcome of very low frequency BWSTT and the
      interaction of BWSTT with other interventions.

PMID- 20037220
TI  - Age-related comparisons of people with multiple sclerosis: demographic, disease,
      and treatment characteristics.
AB  - OBJECTIVE: To determine if the demographic characteristics and health care needs
      of younger people with MS differ from older people with MS. PARTICIPANTS: The
      study analyzed enrollment data from the NARCOMS Registry to compare 1,987 younger
      adults with MS (30 years and younger) to 29,245 other adults with MS (over 30
      years). METHODS: Analyses of the NARCOMS data focused on descriptive
      characteristics of these adults with MS, using a t-test to identify any
      statistically significant age-related differences in means and a chi-squared test
      to identify any statistically significant age-related differences in proportions.
      RESULTS: A significantly larger proportion of younger adults with MS were female
      and African American compared to other adults with MS. We found significant age
      related differences in the expression of physical disability domains but few
      significant age-related differences in symptoms of depression. We also observed
      significant age-related differences in the utilization of health providers, with
      larger proportions of other adults with MS treated by internists, urologists,
      rehabilitation specialists, and physical and occupational therapists.
      CONCLUSIONS: The comprehensive care of younger adults with MS should include
      monitoring for mental health conditions and the availability of mental health
      services.

PMID- 20037221
TI  - Velopharyngeal function in adult speakers of Portuguese diagnosed with multiple
      sclerosis.
AB  - OBJECTIVE: The primary aim of the present investigation was to obtain the
      nasalance score in Portuguese speakers with multiple sclerosis (MS) in order to
      identify velopharyngeal impairments and to enhance clinicians' ability to employ
      appropriate therapy strategies for speech disorders in MS. DESIGN: Perceptual
      assessments (speech sample analysis) and instrumental technique (Nasometer) were
      performed. Two passages were constructed in the Portuguese Language: one similar
      to the Grandfather Passage for perceptual assessments and the other similar to
      the Zoo Passage for the nasalance score. PARTICIPANTS: Seventy (70) adult
      Portuguese speakers with MS and seventy five (75) nonneurologically disordered
      Portuguese speakers were involved in this study. RESULTS/CONCLUSION: The mean
      nasalance score of the MS participants was found to be significantly higher than
      of the control group, confirming velopharyngeal dysfunction in the Portuguese
      speakers group with MS. The results in this study contrast with a low incidence
      of velopharyngeal impairment present in English speakers with MS. These findings
      are discussed with respect to the degree of hypernasality and the potential
      influence of these impairments on the verbal output of the speakers of
      Portuguese.

PMID- 20037222
TI  - "Patternizing" standards of sit-to-stand movements with support in cerebral
      palsy.
AB  - OBJECTIVE: By utilizing "patternizing" standards, this study attempted to obtain
      objective evaluation index of sit-to-stand (STS) movements of children with
      cerebral palsy (CP). In hopes that this understanding can lead to a standardized
      and effective physical therapy treatment of CP STS movements. DESIGN: The
      subjects were 50 children with CP, aged from three years and two months to twelve
      years and four months, mean age nine years and eleven months. The control group
      consisted of ten healthy children, aged from four years and five months to eleven
      years and ten months, mean age seven years and two months. In the analysis,
      firstly, pictures of the subjects' (CP and control group) STS movements were
      taken from the side with one digital video camera. Next, these STS movements were
      classified into two phases (first phase, sitting position to hip off the seat;
      second phase, hip off the seat to standing position), and the state of the
      subjects' extremities was evaluated by 15 items. Based on these 15 items,
      characteristics of STS movements were identified and recorded as YES or NO.
      Finally, using SPSS (version13), cluster analysis was conducted. RESULTS: The
      subjects' STS movements were classified into five aggregate groups. CONCLUSION:
      From these findings, it was possible to distinguish the characteristics and
      differences of STS movements in healthy children and CP subjects. Moreover, the
      CP subjects were also able to be classified into four groups based on their
      shared characteristics of STS movements.

PMID- 20037223
TI  - Short-term effects of vibration therapy on motor impairments in Parkinson's
      disease.
AB  - Recent studies have suggested that vibration therapy may have a positive
      influence on motor symptoms in individuals with Parkinson's disease (PD).
      However, quantitative evidence of these benefits is scarce, and the concept of
      "whole-body" vibration in these studies is vague. The objectives of the current
      study were to evaluate the influence of vibration on motor symptoms and
      functional measures in PD by delivering sound waves to the entire body. We
      delivered whole body sound wave vibration to 40 individuals with PD using a
      Physioacoustic Chair, a piece of equipment with speakers spaced throughout the
      chair permitting a series of programmed low frequency sound waves through the
      body. Using a parallel cross-over design we utilized the Unified Parkinson's
      Disease Rating Scale (UPDRS), quantitative gait assessments, and a grooved
      pegboard for upper limb control. Improvements were seen in all symptom, motor
      control and functional outcome measures at the time of assessment. Specifically,
      a significant decrease in rigidity, and tremor were shown, as well as a
      significant increase in step length and improved speed on the grooved pegboard
      task. Results of this initial investigation provide support for vibration therapy
      as a non-pharmacological treatment alternative. Long-term benefits of vibration
      therapy will require further research.

PMID- 20037224
TI  - Effects of errorless skill learning in people with mild-to-moderate or severe
      dementia: a randomized controlled pilot study.
AB  - This pilot study examines whether learning without errors is advantageous
      compared to trial-and-error learning in people with dementia using a procedural
      task and a randomized case-control design. A sample of 60 people was recruited,
      consisting of 20 patients with severe dementia, 20 patients with mild-to-moderate
      dementia and 20 participants without dementia. The participants had to acquire a
      novel procedural problem-solving task with the help of cues (errorless learning)
      or with cues only given in case an error was made (trial-and-error learning). The
      number of steps completed without assistance immediately after errorless or trial
      and-error learning and after a delay of 1-3 days was recorded. Overall
      performance was better after errorless learning compared to trial-and-error
      learning (p=0.012), with effect sizes being largest in the mild-to-moderate
      dementia group after delayed testing (d=1.61). The effects of errorless learning
      were larger after delayed testing. We conclude that errorless learning of a
      procedural task results in a better performance than learning with errors. This
      study is the first to use a controlled group design to show such a benefit in
      patients with dementia. These findings can be extended to the acquisition of
      tasks that are relevant for everyday-life functioning, having important
      implications for dementia care.

PMID- 20037226
TI  - Ergonomics.

PMID- 20037225
TI  - Enhancing quality of life through Universal Design.
AB  - OBJECTIVES: To inform clinicians, caregivers and researchers involved with
      assessing and treating individuals with neurological disabilities of the benefits
      of universal design in enhancing quality of life. The improvement of quality of
      life has the potential to benefit the individuals with neurological disabilities
      and those whose lives overlap and intersect with those individuals. METHODS:
      Literature and design reviews are used as a foundation for a model for
      incorporating and leveraging universal design to the benefit of the patient's
      social sphere, which includes caregivers, family members and medical staff. By
      matching patients varied abilities with universal design solutions, the model of
      universal design benefitting the patients' social sphere will be demonstrated.
      RECOMMENDATIONS: Recommendations are made for clinicians and researchers that
      they may use in their practices and investigations in three areas: 1) educating
      patients about the benefits of universal design, 2) helping inform patients how
      to leverage universally designed products and approaches in their lives and
      living spaces and 3) understanding how to incorporate universal design principles
      into research and clinical spaces as demonstration pieces for patients.

PMID- 20037227
TI  - FAST ERGO_X - a tool for ergonomic auditing and work-related musculoskeletal
      disorders prevention.
AB  - Work-related musculoskeletal disorders associated with repetitive and strenuous
      working conditions continue to represent one of the biggest occupational problems
      in companies. Despite the variety of efforts to control them, including
      engineering design changes, organizational modifications and working methods
      training programs, work-related musculoskeletal disorders account for a huge
      amount of human suffering and economic costs to companies and to healthcare
      systems. This paper presents an ergonomic analysis tool, FAST ERGO_X, designed to
      support ergonomic auditing activities related with work-related musculoskeletal
      disorders. This tool can be used to analyze workplaces regarding potential
      ergonomic risk factors. The FAST ERGO_X is a fuzzy expert system designed to help
      the identification, assessment and control of the risk factors present in the
      work system, due to lack of adequate ergonomics. Based on objective and
      subjective data, the system evaluates the risk factors that can lead to the
      development of work-related musculoskeletal disorders, and presents the findings
      resulting from such evaluation. The system also presents recommendations to
      eliminate or at least reduce the risk factors present in the work situation under
      analysis.

PMID- 20037228
TI  - Workplace accommodations: occupational therapists as mediators in the interactive
      process.
AB  - Employers are required under the Americans with Disabilities Act to provide
      qualified individuals with disabilities workplace accommodations if needed to
      enable their performance of essential job functions, maintain successful
      employment, and effectively contribute to the workforce and society. The Equal
      Employment Opportunity Commission and many federal courts recommend an
      "interactive process" between the employee and employer, to facilitate effective
      accommodations. Research demonstrates, however, that often the parties to the
      process are uncertain of their roles and responsibilities. Similarly, court
      decisions have not uniformly clarified the specific requirements of the
      interactive process or alternate best practices to achieve an effective outcome.
      This article asserts that an occupational therapist with special training in
      ergonomics may make a significant contribution to identifying and implementing
      effective workplace accommodations, by mediating the interactive process between
      employer and employee. This unique role is illuminated by examination of the
      occupational therapist's professional expertise implementing a successful
      accommodation (case study) contrasted with an unsuccessful accommodation process
      that required litigation to resolve. Furthermore, we discuss the role of legal
      mediation principles in the occupational therapist's practice, suggesting ways to
      improve accommodation outcomes and avoid litigation. Recommendations for future
      research and practice are presented.

PMID- 20037229
TI  - Reflecting on a program of participatory ergonomics interventions: a multiple
      case study.
AB  - Evaluations of participative ergonomics (PE) interventions have reported mixed
      results, potentially due to both program and theory deficits. In a multiple case
      study of four worksites in different companies using a quasi-experimental
      approach, we examined process, implementation, and effects. The process
      evaluation was based upon fieldwork and interviews with approximately 90 persons.
      Implemented changes were documented by PE teams and intensity judged by the
      research team. The effect evaluation was performed using questionnaire-based
      measures (physical effort, influence, pain and potential confounders) among
      cohorts present both before and after the changes (N=258). Ergonomic change teams
      (ECTs) faced challenges securing employees' time, varying management commitment
      and significant production pressures. Nevertheless they actively introduced
      between 10 and 21 changes over 10-20 months of activity. Limited intensity of
      exposure reduction was observed, resulting in no discernible effects on physical
      effort or pain among the employees. Potential reasons that may account for
      limited effects and lessons for workplace parties, practitioners, and
      intervention researchers are discussed.

PMID- 20037230
TI  - Characterizing the intensity of changes made to reduce mechanical exposure.
AB  - Interventions to prevent musculoskeletal disorders by reducing mechanical
      exposures may range from equipment adjustments, through changing workstations and
      equipment or implementing administrative controls, to the design and redesign of
      work processes. Although generally positive, the literature reports mixed results
      for the effects of such workplace interventions on musculoskeletal disorders. We
      propose that an important factor which influences these results is the change
      intensity. This construct includes: the body part(s) affected, the size of
      exposure magnitude reduction in the particular task or tasks involved in the
      change, the time fraction of the job to which the change applies, the coverage of
      the change (proportion of the workforce affected), and the adherence (if
      applicable) by the workforce to the change. The intensities of changes recently
      completed as part of a participatory ergonomics research program were
      characterized using this approach. Intensity scores were estimated based upon
      these parameters for peak and cumulative mechanical exposures. Changes affecting
      a production system re-design and re-configuration were judged to have medium to
      high intensity, while most other changes were judged to be of small intensity.
      Comparisons are made to the intensity of changes determined from reports in the
      published literature. Factors which maximize intensity as well as potential
      barriers to achieving higher intensities are described.

PMID- 20037231
TI  - Nonlinear behavior of the center of pressure in simulated standing on elevated
      construction beams.
AB  - This study investigated the effects of width of construction beams and single
      hand load holding task conditions on nonlinear behavior of the foot center of
      pressure (COP) exerted on the beam. The foot COP, defined as the point of
      application of the result of vertical forces acting on the surface of foot
      support, was measured in the lateral direction under simulated standing task
      conditions. Twelve healthy male subjects were asked to hold a load of 6.8 kg and
      11.3 kg while standing on the elevated construction beams with widths of 10 and
      22.5 cm (4 and 9 inches, respectively) under low and high foot separation (foot
      step). The results showed that both beam width and single-hand load carrying
      conditions had significant effects on the observed nonlinearity of the foot
      center of pressure exerted on the beam. Standing on the narrow beam resulted in
      higher level of chaotic behavior of COP compared to the wide beam condition. The
      nonlinearity of the COP exerted by the forward (left) foot was higher for the
      narrow beam condition. For both beams, the nonlinearity of the COP exerted by the
      forward (left) foot was consistently higher than the COP exerted by the backward
      (right) foot. Furthermore, for both beams, single-handed holding of the 11.3 kg
      load resulted in higher levels of COP nonlinearity than carrying 6.8 kg or no
      load at all. The study results indicate that nonlinear dynamics behavior of the
      forward foot under single-handed high load holding condition may be critical to
      preserving lateral stability during standing at the construction beams.

PMID- 20037232
TI  - The influence of job rotation and task order on muscle fatigue: a deltoid
      example.
AB  - Despite frequent use in industry, job rotation lacks robust confirmation as an
      effective method to limit exposure. This study investigated two tasks that
      involved the deltoid muscle. We examined two major factors in the context of
      muscle fatigue: the presence of rotation between tasks, and the order of task
      rotation if rotation was present. Participants performed four task combinations
      (coded AA, AB, BA, BB) of two tasks that were intended to produce fatigue (A:
      repetitive shoulder flexion; B: repetitive shoulder abduction). All tested
      conditions resulted in lower maximum force production capability (mean range of
      78-88% of original strength), in this order of decreasing magnitude: BB --> AB -
      > BA --> AA, though differences between successive levels were not always
      significant. Specific muscle results supported this progression of strength
      decreases. For tasks with different muscular demands (AB and BA), it was less
      fatiguing to rotate between them than to only perform the more demanding task
      (BB). The order of rotation between tasks (AB vs. BA) did not influence muscle
      fatigue indicators. These findings help to assess the effectiveness of rotating
      between different tasks in reducing muscular fatigue or exposure. They also
      indicated a low apparent influence of task order on terminal fatigue
      characteristics for the task combinations evaluated.

PMID- 20037233
TI  - Mountain rescue stretchers: usability trial.
AB  - In the UK mountain rescues are carried out by highly trained volunteers in all
      weather conditions and at any time of the day/night. They interface with other
      services when they hand over the casualty to either land or air ambulances. The
      design of the stretcher is important to the safety of both the volunteers and
      casualties. This paper reports a usability trial to evaluate the features of
      mountain rescue stretchers and identify characteristics for future design. Two
      mountain rescue teams in the English Lake District participated in a five week
      field experiment. Data were collected using postural analysis with Rapid Entire
      Body Analysis, Body Part Discomfort Surveys, Rated Perceived Exertion and focus
      groups to compare the performance of four stretchers: Split Thomas, Ferno Titan,
      MacInnes mark 6 and MacInnes mark 7. None of the stretchers had an overall
      advantage, with benefits for some features counterbalanced by disadvantages
      resulting from others. All the stretchers produced shoulder discomfort with the
      Split Thomas and MacInnes 6 lowering the postural risks through the use of
      skids/wheel in the carrying phase. The key design features for future MR
      stretchers include: reduced unloaded weight (e.g. light weight materials and mesh
      platforms); undercarriage system to reduce the carrying load; adjustable handles
      at the front and back positions; flexible carrying system with an optional
      harness attachment; ease of assembly in adverse environmental conditions; large
      carrying capacity. It is suggested that military emergency evacuation should be
      considered in addition to mountain rescue tasks to identify a larger commercial
      market for development.

PMID- 20037234
TI  - Effect of chair design on ratings of discomfort.
AB  - The purpose of this study was to determine if ratings of discomfort differ over
      time between two ergonomic chairs of the same approximate cost. Twenty
      participants from a metropolitan university sat on two types of ergonomic chairs
      for 90~minutes in each of two sessions while performing typing, reading, and
      writing tasks. Repeated measures three-way and two-way analyses of variance were
      used to examine the effect of the ergonomic chair design on rating of discomfort.
      Data were collected using the General Comfort Rating Scale (GCRS) and the Body
      Part Discomfort Rating Scale (BPDRS), which were administered at 0, 30, 60, and
      90 minute marks of each session. The results revealed: 1) discomfort was not
      related to the type of chair, 2) discomfort increased over time, 3) discomfort
      was influenced by the task performed while sitting, 4) discomfort level decreased
      when switching between different chairs, and 5) most discomfort was reported in
      the low back and lower arms.

PMID- 20037235
TI  - Ergonomics and sitting at work.
AB  - Many factors influence the performance at the workplace. The immediate interface
      between the user and the equipment is, perhaps, the most important. Hence, the
      arrangements of the seat and work point are critical.Factors which cause
      discomfort and injury to seated workers are described and, from the behaviour of
      the spine under load, a better seat design is presented. Its use by a wide
      variety of workers makes it necessary to introduce increased adjustability,
      beyond that normally part of conventional seat design. The application of the new
      design in two cases in industry, as well as its introduction in schools, is
      briefly covered.

PMID- 20037236
TI  - Work related psychosocial risks and musculoskeletal disorders: potential risk
      factors, causation and evaluation methods.
AB  - Musculo Skeletal Disorders (MSDs) are the focus of considerable attention and
      research in occupational health, which is in part due to high prevalence rates
      and associated costs. In the United States, the total cost associated with MSDs
      increased from $81 billion in 1986 to $215 billion in 2005 [3]. Epidemiological
      studies have repeatedly shown associations between work-related psychosocial
      factors and MSDs, and the role of psychosocial factors and stress in these
      disorders has received increased attention. Several reviews have reported
      associations between MSDs and work-related psychosocial factors such as high
      workload/demands, high perceived stress levels, low social support, low job
      control, low job satisfaction and monotonous work. Several theories have been
      proposed to explain the apparent relationship between stress and MSDs in the
      workplace from a biological perspective. These include the biopsychosocial model
      of job stress, the hyperventilation theory, the migraine theory, the muscle
      spindle theory and the Cinderella hypothesis. Within the literature, a vast array
      of questionnaires have been developed in an attempt to measure the psychosocial
      factors that occur within the workplace. This article presents a discussion of
      existing knowledge of the psychosocial risk factors potentially linked to MSDs
      and potential pathways to injury. A discussion of evaluation approaches used to
      estimate psychosocial risk exposures in workplaces is also presented.

PMID- 20037239
TI  - From the editor.

PMID- 20037240
TI  - A narrative insight into disability pensioners' work experiences in highly gender
      segregated occupations.
AB  - This study examined some plausible explanations for the higher rates of ill
      health seen in extremely gender-segregated occupations. The focus was on the work
      experiences of disability pensioners with last jobs prior to pensioning
      characterized by segregated conditions (i.e., less than 10% of the employees of
      their own sex). Seven interviews were subjected to qualitative content analyses
      focusing on aspects of health selection, gender differences in work tasks, and in
      the work situation. The results show a negative health selection into occupations
      in which the participants constitute an extreme minority. There were some
      differences in work tasks between the gender in extreme minority and the other
      gender. Exposure to different stress factors related to the minority status
      included increased visibility, performance pressure, and harassment. Gender had
      been of main importance for differences in exposure, for assigning work tasks,
      and for interaction dynamics between the groups in majority and extreme minority.
      CONCLUSIONS: A combination of negative health selection, gender marking of work
      tasks, and group interaction dynamics related to group proportions and gender may
      play a role in cumulative health risks. Additional longitudinal studies are
      needed to identify mechanisms and interactions in this context in order to better
      understand possible relationships between occupational gender segregation and
      increased health risks.

PMID- 20037241
TI  - A revised back compressive force estimation model for ergonomic evaluation of
      lifting tasks.
AB  - Occupational back pain and injury are common and costly issues. Biomechanical
      models are often used to quantify job risk by estimating back muscle forces. In
      general, the most accurate models are also the most complex, creating demand for
      models that are both straightforward and accurate. An existing, basic hand
      calculation back compressive force estimation model (HCBCF v1.0) was revised in
      two iterations to reduce the error induced by original simplifying assumptions.
      Lifting tasks (n=6000) from observational data were used to compare the HCBCF
      models with the University of Michigan 3D Static Strength Prediction Program
      (3DSSPP) The greatest r(2) (0.97) between the HCBCF v1.2 and the 3DSSPP was
      achieved with gender-specific equations designed to account for differences
      between males and females and a more detailed estimation of torso flexion angle
      and upper body mass center location. This gender-specific back compression and
      risk estimation model is a relatively simple alternative to computer-based back
      compressive force models. In addition the hand-calculation can be used as a
      general survey tool to determine which jobs should be analyzed with more
      sophisticated computer-based models.

PMID- 20037242
TI  - Occupational injuries reported in a Canadian university setting: a five year
      retrospective study.
AB  - Research examining occupational injuries of university employees is limited, with
      previous work in the education sector focusing primarily on students and athletic
      teams. The current study examined occupational injuries over a five year period
      to determine the magnitude and nature of occupational injuries in a Canadian
      university with a view to developing prevention and intervention strategies.
      Findings suggested that women in full-time positions reported more injuries than
      men, and that as employees' level of experience increased the incidence of injury
      decreased. Analysis of injury characteristics revealed that the fingers, back and
      hand were the most frequently injured sites typically as a result of being struck
      or caught by an object, a slip/trip, or overexertion. These injuries resulted
      predominantly in an acute soft tissue injury requiring medical attention. Over
      the five year study period, food services, housekeeping and clerical staff filed
      the greatest number of accident/incident reports. Future investigations should
      employ a prospective approach which would allow researchers to determine
      variables of interest, ensure adequate data collection, and aim to improve the
      generalizability of research findings in this area.

PMID- 20037243
TI  - The impact of breast cancer among Canadian women: disability and productivity.
AB  - Each year over 20,000 Canadian women are diagnosed with breast cancer. Many
      breast cancer survivors anticipate a considerable number of years of potential
      participation in the paid labour market, therefore, the link between breast
      cancer survivorship and productivity deserves serious consideration. The
      hypothesis guiding this study is that arm morbidities such as lymphedema, pain,
      and range of motion limitations are important explanatory variables in survivors'
      loss of productivity. The study draws from a larger longitudinal research project
      involving over 600 breast cancer survivors in four geographical locations across
      Canada. The study's regression results indicate that, after adjusting for
      fatigue, breast cancer stage, and geographical location, survivors with range of
      motion limitations and arm pain are more than two and half times as likely to
      lose some productivity capacity as compared to counterparts with no arm
      morbidity. The findings make a compelling argument for the necessity of adequate
      rehabilitation programs delivered at crucial times in breast cancer survivors'
      recovery. The study's unexpected finding that geographical location is a highly
      significant predictor of changes in productivity among breast cancer survivors is
      interpreted as a factor of the regulatory framework governing employment
      relationships in the four different jurisdictions.

PMID- 20037244
TI  - Typical whole body vibration exposure magnitudes encountered in the open pit
      mining industry.
AB  - According to recent research, a causal link has been established between
      occupational exposure to whole body vibration and an increased occurrence of low
      back pain. To aid in the further development of an in-house health and safety
      program for a large open pit mining facility interested in reducing back pain
      among its operators, whole body vibration magnitudes were characterized for a
      range of jobs. Specifically, thirty-five individual jobs from five different
      areas across the facility were evaluated for tri-axial acceleration levels during
      normal operating conditions. Tri-axial acceleration magnitudes were categorized
      into thirteen job groups. Job groups were ranked according to exposure and
      compared to the ISO 2631-1 standard for health risk assessment. Three of the
      thirteen job groups produced tri-axial acceleration magnitudes below the ISO 2631
      1 low/moderate health caution limit for a twelve hour exposure. Six of the
      thirteen job groups produced exposures within the moderate health risk range.
      Four job groups were found to subject operators to WBV acceleration magnitudes
      above the moderate/high health caution limit.

PMID- 20037245
TI  - Stress factors affecting academic physicians at a university hospital.
AB  - Research is limited regarding occupational stress in academic physicians;
      professionals whose work situation includes the three areas of clinical practice,
      research, and teaching. The aim of this study was to gain knowledge of factors
      experienced as stressful by academic physicians employed by a university
      hospital. A questionnaire assessing the frequency and intensity of 36 potentially
      stressful factors was sent to all 157 academic physicians who were employed at
      the Linkoping University Hospital, Sweden. The response rate was 77%. Both a high
      frequency and intensity of stress was experienced by 66% of the academic
      physicians in relation to "time pressure" and by almost 50% in connection with
      both "find time for research" and having "conflict of interest between different
      work assignments". Moreover, physicians in the higher age group and those who had
      attained a higher academic position experienced less stress. The female
      participants experienced more stress than the males due to gender-related
      problems and to variables associated with relationships at work. More knowledge
      is needed to determine the consequences of this finding and to identify coping
      strategies used for handling such stress.

PMID- 20037246
TI  - Exploring consequences of sickness absence - a longitudinal study on changes in
      self-rated physical health.
AB  - Women experience sickness absence more often than men, but few studies have
      addressed the possibility that the sick-leave period itself could be regarded as
      an exposure with possible positive or negative consequences on health. The aim
      was to explore the association between experience of sickness absence and self
      rated physical health. Interview data from population samples in 1990 and 1995 of
      women born in 1935, 1945, 1955 and 1965 (n=231) were used. 'Any sick-leave' and
      'Long sick-leave' were used as exposure measures and analyzed in relation to
      change in self-rated physical health with multivariate logistic regression,
      adjusting for age and prior sickness absence. Separate analyses were performed
      for women with psychiatric disorders (DSM-III-R) and different level of domestic
      responsibility. The proportion reporting good health at baseline and follow up
      were lower when experienced sickness absence compared to those who had not. For
      women exposed to long sick-leave, the OR for remained poor health were 4.1 (95%
      CI 1.1-15.4), and for women with psychiatric disorders, the OR for a change from
      poor to good health was 9.9 (1.7-58.5). Women with high level of domestic
      responsibility and exposed to long sick-leave, had increased ORs for both a
      positive and negative change in health. This explorative study contributes to the
      sparse knowledge of consequences on health of sickness absence.

PMID- 20037247
TI  - Prevalence of work related upper limb disorders in hairdressers: a cross
      sectional study on the influence of working conditions and psychological,
      ergonomic and physical factors.
AB  - A cross sectional study where 145 hairdressers were interviewed for the
      occurrence of work related upper limb disorders (WRULD). The interview features
      for engagement, burnout and workaholism, as well as asks for general health and
      working conditions. The BMI, the hand size and gripping force of each worker was
      obtained. WRULD was present in 41%. It was significantly correlated with burnout
      and workaholism. Surprisingly it was not altered by engagement or by the use of
      ergonomic equipment. Morphological features (BMI), hand size and gripping force,
      were not related to the occurrence of WRULD.

PMID- 20037248
TI  - Tai Chi workplace program for improving musculoskeletal fitness among female
      computer users.
AB  - BACKGROUND: Workplace computer use has increased dramatically in recent years and
      has been linked to musculoskeletal disorders, a leading cause of work disability
      and productivity losses in industrialized nations. Tai Chi is a simple,
      convenient workplace intervention that may promote musculoskeletal health without
      special equipment or showering, yet no study has investigated Tai Chi as a
      workplace physical exercise for health promotion. OBJECTIVE: To examine the
      effects of a workplace Tai Chi (TC) intervention on musculoskeletal fitness and
      psychological well-being among female university employees who are computer
      users. METHODS: The exercise program consisted of two 50 minute TC classes per
      week for 12 consecutive weeks during the months of May-August 2007. Fifty-two
      participants were enrolled in a class conducted on campus by a professional TC
      practitioner during the lunch hour. Socio-demographic characteristics, including
      information on age, marital status, ethnicity, job category and perceived overall
      health were collected from all participants. Fitness testing conducted by
      qualified personnel was assessed pre- and post-program. The tests included
      resting heart rate, resting blood pressure, anthropometric measures,
      musculoskeletal fitness and back fitness. Psychological well-being was assessed
      by the Perceived Stress Scale pre- and post-program. RESULTS: There were
      significant positive results in several areas including resting heart rate, waist
      circumference and hand grip strength. Results showed that the TC program was
      effective in improving musculoskeletal fitness and psychological well-being.
      CONCLUSIONS: Significant improvements in physiological and psychological measures
      were observed, even at the large class sizes tested here, suggesting that TC has
      considerable potential as an economic, effective and convenient workplace
      intervention.

PMID- 20037249
TI  - A physical fitness programme during paid working hours - impact on health and
      work ability among women working in the social service sector: a three year
      follow up study.
AB  - In order to study the influence of a physical fitness programme on work ability
      among women employed in the social sector an intervention was offered to 205
      women working in the social care sector in a municipality in Sweden. The
      reference group comprised 165 women from the same sector working in another
      municipality. All participants were employed and answered questionnaires at
      baseline and after 36 months. For women younger than 45 years, work ability and
      general health improved significantly while for women, 45 years or older, future
      work expectations improved. For women with less musculoskeletal pain,
      improvements were observed regarding future work expectations, as well as work
      ability and general health while for women with more musculoskeletal pain,
      improvements were observed for general health and future work expectations. Well
      structured physical fitness programmes at the worksite can be useful in
      contributing to individual's experiences of improvements in their own capacity as
      well as increased health and wellbeing.

PMID- 20037250
TI  - The adverse effects of psychosocial constraints at work: a participatory study to
      orient prevention to mitigate psychological distress.
AB  - Studies conducted with the JDC (job demand-control) or ERI (effort-reward
      imbalance) models highlight the links between constraints in the psychosocial
      work environment and psychological distress. However, the underlying mechanisms
      are not very well understood. The present participatory qualitative study
      explored these mechanisms with a view to identifying both the processes at work
      in these relationships and some targets for problem prevention. This
      investigation was conducted with white-collar workers from a public service
      organisation within one Canadian province (Quebec) who participated in six
      discussion groups during an intervention designed to reduce psychosocial
      environment constraints. The data gathered in these groups was subjected to
      content analysis through thematic categorization. The findings indicate that
      psychosocial constraints take root in situations that adversely affect subjective
      dimensions relating to personal and professional experience. An interpretive
      model is proposed on the basis of these findings, which helps to elucidate the
      dynamic relationships that exist among the various aspects of work experience
      that can lead to psychological distress. From this model, some targets for
      problem prevention have emerged.

PMID- 20037251
TI  - Description and clinical studies of a device for the instantaneous detection of
      office-place stress.
AB  - Occupational stress is universally experienced and is emerging as a major risk
      factor for physical and mental illness and a key factor in poor work performance
      and low job satisfaction. However, the technology does not currently exist to
      unobtrusively measure occupational stress in real-time. Here, we describe the
      design and clinical validation of an automated high-definition thermal imaging
      system that can be used to quantify human stress, remotely and instantaneously.
      Healthy human subjects underwent a computer-based version of the Stroop-color
      conflict test, which is a validated stress provocation test, in an experimental
      office facility. In separate experiments, the same subjects completed a mental
      arithmetic challenge. The thermal signal associated with stress provocation is
      near-instantaneous corrugator warming. The stress response was detected in all
      subjects for all stress-events compared to the respective baselines. Furthermore,
      there was remarkable inter-individual preservation of the corrugator signal with
      stress R(2) = 0.96, P< 0.001). High-definition thermal imaging can be used for
      real-time detection of stress provocation. This technology may prove to be of
      help in ameliorating office-place stress.

PMID- 20037252
TI  - Characteristics associated with duration of employment of persons with
      schizophrenia after first contact with psychiatric services.
AB  - The aim was to explore the demographic and clinical characteristics influencing
      the duration of employment after onset of schizophrenia. Occupational history was
      assessed in persons with schizophrenia (n=102) requesting the status of disabled
      person for the first time. Multivariate analyses were used to explore the
      characteristics independently associated with duration of work after the first
      contact with psychiatric services. Duration of employment was categorized into
      "never worked", "worked less than half of the time", "worked half of the time or
      more". More than half of patients never worked after the first contact with
      psychiatric services. Compared to them, persons who were employed half of the
      time or more were more likely to have a higher educational level and a long
      duration of employment before illness onset. Persons who were employed less than
      half of the time presented with clinical markers of poor prognosis, i.e. higher
      frequency of alcohol use disorder and higher number of hospitalisations. Persons
      unable to keep enduring employment after illness onset may have different needs
      regarding social and rehabilitation management compared to those able to maintain
      a working activity over a long period.

PMID- 20037253
TI  - Understanding work ability: experiences of female assistant nurses in elderly
      care.
AB  - Few studies to date have investigated retained work ability. The aim of this
      explorative study was to describe female assistant nurses' experiences of high
      work attendance over the years The setting is a municipality in mid-Sweden that
      employs 466 female assistant nurses permanently within municipal elderly care. A
      qualitative methodology was chosen and thematic, open-ended, interviews were
      carried out with 12 female assistant nurses. The interviewees were selected from
      the 117 women who had taken the least amount of sick leave over the past five
      years, which meant no sick leave at all or no more than 5 days. The interviews
      were transcribed verbatim, and thereafter a content analysis was carried out.
      Three main themes connected with the aim of the study emerged from the
      interviews: "a desirable job, despite low status", "supportive social networks",
      and "coping ability". In order to strengthen work ability among female employees
      in elderly care, the findings indicate that it is crucial to support mobility in
      working life, and to promote social support and networks at the workplace and in
      private life, as well as a coping-oriented approach to health issues and social
      life.

PMID- 20037255
TI  - Validity of using body mass index as a surrogate measure of abdominal obesity.

PMID- 20037256
TI  - Patient-based outcomes using the Walking Impairment Questionnaire for patients
      with peripheral arterial occlusive disease treated with Lipo-PGE1.
AB  - BACKGROUND: Patients with peripheral arterial occlusive disease (PAD) experience
      deteriorating ambulatory function and consequently impaired quality of life
      (QOL). QOL in patients receiving prostaglandin E(1) in lipid microspheres (lipo
      PGE(1); Liple) for the treatment of PAD has not been evaluated using the Japanese
      version of the Walking Impairment Questionnaire (WIQ). METHODS AND RESULTS: Data
      from 169 patients (98 men, 71 women; mean [median] age, 74+/-10 [74] years) with
      an ankle-brachial pressure index <0.9 were analyzed. WIQ scores and symptom
      scores significantly improved after lipo-PGE(1) treatment (P<0.01). Physicians'
      assessments of global improvement significantly correlated with all 4 WIQ
      subscales (R< or =0.31). CONCLUSIONS: WIQ is a valid tool for evaluating
      therapeutic response in patients with PAD. Lipo-PGE(1) improves QOL as evaluated
      by patients themselves.

PMID- 20037257
TI  - Association of endothelial nitric oxide synthase gene polymorphisms with early
      onset ischemic stroke in South Indians.
AB  - AIM: The aim of this study was to investigate the association of T-786C, G894T
      and 4a/b polymorphisms in the endothelial nitric oxide synthase (eNOS) gene with
      early-onset ischemic stroke in South Indians. METHODS: We enrolled 177 patients
      diagnosed with ischemic stroke aged between 15 to 45 years and 219 age- and
      gender-matched healthy controls. Genotypes of eNOS T-786C, G894T and 4a/b were
      identified by polymerase chain reaction and restriction fragment length
      polymorphism. RESULTS: The allele and genotype frequencies of eNOS 4a/b, T-786C
      and G894T did not differ significantly in the patient group compared to controls.
      Logistic regression analysis indicated the 4a allele to be an independent
      predictor of ischemic stroke in females (dominant model: OR, 2.46; 95% CI, 1.11
      to 5.43; p=0.026). Marked differences were found in the prevalence of the minor
      alleles of the three variants when comparing the South Indian population with the
      reported frequencies from Caucasians. There was also a contrast in the
      frequencies of 4ab and T-786C variants from other Asians. The genotypes of all
      three variants were found to be in Hardy-Weinberg equilibrium. There was a lack
      of significant linkage disequilibria among the variants, and none of the
      estimated haplo-types increased or decreased the risk of ischemic stroke.
      CONCLUSION: The eNOS intron 4a/b polymorphism can predict early-onset ischemic
      stroke in south Indian women.

PMID- 20037258
TI  - Cumulative effects of weather on stroke incidence: a multi-community cohort study
      in Japan.
AB  - BACKGROUND: Although seasonal variation in stroke incidence has been reported, it
      is not known whether year-long exposure to particular meteorological conditions
      affects the risk of stroke independently of conventional cardiovascular risk
      factors. METHODS: We conducted a cohort study involving 4849 men and 7529 women
      residing in 12 communities dispersed throughout Japan. Baseline data were
      obtained from April 1992 through July 1995. Follow-up was conducted annually to
      capture first-ever-in-life stroke events. Weather information during the period
      was also obtained for each community. Multilevel logistic regression analysis was
      conducted to evaluate the association between stroke incidence and each
      meteorological parameter adjusted for age, obesity, smoking status, total
      cholesterol, systolic blood pressure, diabetes, and other meteorological
      parameters. RESULTS: Over an average of 10.7 years of follow-up, 229 men and 221
      women had stroke events. Among women, high annual rainfall (OR per 1000 mm, 1.46;
      95% confidence interval, 1.05-2.03), low average ambient temperature (OR per 1
      degrees C, 0.79; 0.66-0.94), and number of cold days per year (OR per 10 days,
      3.37; 1.43-7.97) were associated with increased risk of stroke incidence,
      independent of conventional risk factors. Among men, number of cold days (OR per
      10 days, 1.07; 1.02-1.12) was associated with an increased risk of stroke
      incidence, but the association became nonsignificant after adjustment for other
      risk factors. Similar results were obtained for cerebral infarction and cerebral
      hemorrhage. CONCLUSIONS: Long-term exposure to some meteorological conditions may
      affect the risk of stroke, particularly in women, independent of conventional
      risk factors.

PMID- 20037259
TI  - Estimation of trans fatty acid intake in Japanese adults using 16-day diet
      records based on a food composition database developed for the Japanese
      population.
AB  - BACKGROUND: The Standard Tables of Food Composition in Japan do not include
      information on trans fatty acids. Previous studies estimating trans fatty acid
      intake among Japanese have limitations regarding the databases utilized and diet
      assessment methodologies. We developed a comprehensive database of trans fatty
      acid food composition, and used this database to estimate intake among a Japanese
      population. METHODS: The database was developed using analytic values from the
      literature and nutrient analysis software encompassing foods in the US, as well
      as values estimated from recipes or nutrient compositions. We collected 16-day
      diet records from 225 adults aged 30 to 69 years living in 4 areas of Japan.
      Trans fatty acid intake was estimated based on the database and the 16-day diet
      records. RESULTS: Mean total fat and trans fatty acid intake was 56.9 g/day
      (27.7% total energy) and 1.7 g/day (0.8% total energy), respectively, for women
      and 66.8 g/day (25.5% total energy) and 1.7 g/day (0.7% total energy) for men.
      Trans fatty acid intake accounted for greater than 1% of total energy intake,
      which is the maximum recommended according to the World Health Organization, in
      24.4% of women and 5.7% of men, and was particularly high among women living in
      urban areas and those aged 30-49 years. The largest contributors to trans fatty
      acid intake were confectionaries in women and fats and oils in men. CONCLUSIONS:
      Although mean trans fatty acid intake was below the maximum recommended intake of
      the World Health Organization, intake among subgroups was of concern. Further
      public health efforts to reduce trans fatty acid intake should be encouraged.

PMID- 20037260
TI  - Measuring effort-reward imbalance in school settings: a novel approach and its
      association with self-rated health.
AB  - BACKGROUND: We attempted to apply the model of effort-reward imbalance (ERI) to
      school settings in order to measure students' psychosocial stress and analyze its
      association with self-rated health in adolescents. METHODS: A cross-sectional
      survey was conducted in Kunming, China among 1004 Chinese students (468 boys and
      536 girls) in grades 7 through 12, using a 19-item effort-reward imbalance
      questionnaire. RESULTS: Satisfactory internal consistencies for the scales for
      effort and reward were obtained; the value for the scale for overcommitment was
      acceptable. Factor analysis replicated the theoretical structure of the ERI
      construct in this sample of Chinese students. All 3 scales were associated with
      an elevated odds ratio for diminished self-rated health, and the effect was
      strongest for the effort-reward ratio, as predicted by the theory. Sex and grade
      differences were also observed. CONCLUSIONS: The ERI questionnaire is a valid
      instrument for identifying sources of stressful experience, in terms of effort
      reward imbalance, among adolescents in school settings.

PMID- 20037261
TI  - [Transient elastography, true or false?].

PMID- 20037262
TI  - [Epidemiology and clinical features of acute hepatitis A: from the domestic
      perspective].
AB  - Acute viral hepatitis A has recently become a major public health problem in
      Korea, and the incidence of symptomatic hepatitis A is growing rapidly. With
      improvements in socioeconomic conditions and environmental hygiene, the chances
      of exposure to hepatitis A virus (HAV) during childhood have decreased and, in
      turn, the proportion of young adults with positive anti-HAV has significantly
      decreased. This has led to the incidence of symptomatic acute hepatitis A
      increasing since the late 1990s. The incidence of serious complications including
      fulminant hepatic failure and acute kidney injury has also showed an increasing
      trend. Variation of the genotype of virus isolated from recent hepatitis A
      patients suggests an inflow of the hepatitis virus from other countries. In this
      review article, we present the situation and epidemiology of hepatitis A in
      Korea, and recommend further investigation and policies for vaccination on a
      national level.

PMID- 20037263
TI  - [Clinical efficacy of entecavir therapy and factors associated with treatment
      response in naive chronic hepatitis B patients].
AB  - BACKGROUND/AIMS: Entecavir is a potent and selective guanosine analogue that has
      demonstrated a significant antiviral efficacy against hepatitis B virus (HBV).
      The aim of this study was to characterize the response to entecavir and to
      examine the factors affecting that response. METHODS: We administered 0.5 mg of
      entecavir once daily for more than 12 months to 114 naive chronic hepatitis B
      (CHB) patients. We measured the levels of liver enzymes, serological markers, and
      serum HBV DNA at 3-month interval. RESULTS: Normalization of serum alanine
      aminotransferase levels was observed in 68.5% (76/114), 74.6% (85/114), and 81.6%
      (62/76) of patients after 6, 12, and 24 months of therapy, respectively. HBV DNA
      levels of <50 copies/mL (as evaluated by polymerase chain reaction) were observed
      in 43.9% (50/114), 71.1% (81/114), and 85.5% (65/76) of patients after 6, 12, and
      24 months, respectively. Viral breakthrough was not observed. The rates of HBeAg
      loss and seroconversion were 43.5% (27/62) and 14.5% (9/62), respectively, after
      12 months of therapy, and 56.4% (22/39) and 15.4% (6/39) after 24 months. The
      independent factor associated with PCR negativity was early virologic response
      (EVR; HBV DNA <2,000 copies/mL after 3 months of therapy, P<0.001). The
      independent factors predicting HBeAg loss were found to be serum albumin levels
      (P=0.041) and EVR (P=0.005). CONCLUSIONS: Entecavir induced excellent biochemical
      and virologic responses in naive CHB patients. EVR was an independent factor for
      predicting HBV PCR negativity and HBeAg loss.

PMID- 20037264
TI  - [Comparison of various noninvasive serum markers of liver fibrosis in chronic
      viral liver disease].
AB  - BACKGROUND/AIMS: The aim of this study was to determine the clinical performances
      of noninvasive serum markers for the prediction of liver fibrosis in chronic
      viral liver diseases. METHODS: We analyzed a total of 225 patients with chronic
      viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and
      2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang
      University Guri Hospital between March 2002 and February 2007. Serum was also
      obtained at the time of liver biopsy. Liver fibrosis was staged according to the
      scoring system proposed by the Korean Study Group for the Pathology of Digestive
      Diseases. Various noninvasive serum markers were evaluated, including the
      aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age
      platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant
      score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. RESULTS:
      There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4,
      respectively. The overall diagnostic accuracies of each marker, as determined by
      the area under receiver operating characteristics curves, were APRI=0.822,
      CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV
      collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and
      CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV
      collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3).
      CONCLUSIONS: All noninvasive serum markers evaluated in this study were useful
      for predicting significant or extensive liver fibrosis in chronic viral liver
      diseases. In particular, APRI was most useful for the prediction of significant
      fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

PMID- 20037265
TI  - [Factors associated with liver stiffness in chronic liver disease].
AB  - BACKGROUND/AIMS: Transient elastography is a new noninvasive tool for measuring
      liver stiffness that accurately predicts significant fibrosis and cirrhosis.
      However, several studies have indicated that liver stiffness can be significantly
      influenced by major changes in aminotransferase in patients with chronic viral
      hepatitis. The aim of this study was to determine the factors influencing liver
      stiffness in patients with chronic liver disease. METHODS: We studied 158
      patients with chronic liver disease who underwent transient elastography and
      liver biopsy sampling. Histologic findings on fibrosis and necroinflammatory
      activity in the biopsy specimens were evaluated according to the Korean Society
      of Pathologists Scoring System. Routine biochemical tests were performed
      according to standard methods. RESULTS: Liver stiffness was strongly correlated
      with liver fibrosis stage (Spearman coefficient=0.636, P<0.001), lobular activity
      (Spearman coefficient=0.359, P<0.001), and portoperiportal activity grade
      (Spearman coefficient=0.448, P<0.001). Liver stiffness was significantly
      associated with serum levels of total bilirubin (P=0.025), direct bilirubin
      (P=0.049), gamma-glutamyl transpeptidase (P=0.014), platelet count (P=0.004),
      albumin (P<0.001), and international normalized ratio (P<0.001). Multivariate
      analysis showed that fibrosis stage (B 3.50, P=0.009) and lobular activity grade
      (B 3.25, P=0.047) were independently associated with liver stiffness.
      CONCLUSIONS: Liver stiffness as measured by transient elastography is associated
      with the grade of necroinflammatory activity and the stage of fibrosis,
      irrespective of serum ALT levels.

PMID- 20037266
TI  - [Comparison of radiofrequency ablation and transarterial chemoembolization for
      the treatment of a single hepatocellular carcinoma smaller than 4 cm].
AB  - BACKGROUND/AIMS: Radiofrequency ablation (RFA) is an established curative
      therapeutic modality for unresectable hepatocellular carcinoma (HCC), and
      transarterial chemoembolization (TACE) has been used as a palliative treatment
      for inoperable HCC. It is still unknown whether RFA and TACE are equally
      effective for improving the survival of patients with unresectable HCC that is
      amenable to either treatment. The aim of this retrospective study was to compare
      the clinical impacts of two treatments, and analyze the prognostic factors for
      recurrence and survival. METHODS: Ninety-three patients with a single HCC smaller
      than 4 cm who showed complete responses (complete ablation or complete lipiodol
      tagging) after treatment with RFA (n=43) or TACE (n=50) between January 2002 and
      February 2009 were investigated. Univariate and multivariate analyses were
      performed for 13 potential prognostic factors using the Cox proportional-hazards
      model. RESULTS: The time-to-recurrence rates at 1, 2, and 3 years after treatment
      were 32.9%, 44.3%, and 55.4%, respectively, for the RFA group, and 42%, 68.3%,
      71.7% for the TACE group. The probability of survival at 1, 2, and 3 years was
      97.7%, 77.4%, and 63.1%, respectively, for the RFA group, and 95.9%, 76.1%, and
      60.2% for the TACE group. The time-to-recurrence and overall survival rates did
      not differ significantly between the two treatment groups. A multivariate Cox
      proportional-hazards model revealed that a tumor size larger than 3 cm and lower
      serum albumin levels were independent risk factors for recurrence, and that being
      male, being seropositive for hepatitis B surface antigen, and having a higher
      serum albumin level were independent favorable prognostic factors for survival.
      CONCLUSIONS: TACE and RFA exhibited similar therapeutic effects in terms of
      recurrence and survival for patients with a single HCC smaller than 4 cm, if they
      could exhibited complete responses.

PMID- 20037267
TI  - Transcriptional profiling and Wnt signaling activation in proliferation of human
      hepatic stellate cells induced by PDGF-BB.
AB  - BACKGROUND/AIMS: This study aimed to better understand gene expression profiles
      of human hepatic stellate cell (HSC) activation and the relationship with the Wnt
      signaling pathway. METHODS: The global transcript levels in platelet derived
      growth factor-BB (PDGF-BB)-stimulated hTERT HSCs were analyzed using
      oligonucleotide microarrays. Oligonucleotide microarrays with 19K human oligo
      chips were performed to obtain gene expression profiles associated with
      proliferation in human hTERT HSCs. The microarray data was verified by real time
      quantitative PCR and expression of the components of Wnt signaling was analyzed
      by Western blot. RESULTS: Microarray data showed 243 up-regulated and 265 down
      regulated genes in PDGF-BB-treated HSCs. The changes in expression of glypican3
      and BH3 interacting domain death agonist (BID) mRNA in real time quantitative
      PCR, especially among the highly up- or down-regulated genes, were statistically
      consistent with the microarray data. The Wnt signaling pathway components,
      frizzled10 (FZD10) and calcium/calmodulindependent protein kinase II alpha
      (CAMK2A), showed increased expression in the short time course microarray and the
      up-regulation of FZD10 also occurred at the protein level. Our data showed
      various gene expression profiles during activation of human HSC. CONCLUSIONS: The
      up-regulated expression of FZD10 and CAMK2A suggests that the Wnt/Ca(2+)
      signaling pathway is active in hTERT HSCs and may participate in HSC activation
      and proliferation.

PMID- 20037268
TI  - [A comparison of 24- vs. 48-week peginterferon plus ribavirin in patients with
      genotype 1 chronic hepatitis C].
AB  - BACKGROUND/AIMS: The standard therapy for patients with genotype 1 chronic
      hepatitis C (CHC) is a combination of peginterferon and ribavirin for 48 weeks.
      However, the most appropriate duration of treatment remains to be established
      because of treatment-related side effects and cost. The aim of this study was to
      compare the efficacies of 24- and 48-week treatments, and to assess the efficacy
      of split 24-week therapy (a further 24 weeks of treatment in patients with
      relapse after the initial 24 weeks of treatment). METHODS: A total of 130
      patients with genotype 1 CHC was treated between June 2004 and December 2006.
      Patients with undetectable HCV RNA at 24 weeks of treatment (as assessed by
      qualitative PCR assay; n=101 patients) were allowed to choose either 24 or 48
      weeks as the duration of their treatment; 51 patients chose the 24-week treatment
      regimen and the remainder chose the 48-week regimen. Patients who relapsed after
      24 weeks of treatment were treated for further 24 weeks. The sustained virologic
      response (SVR) of each treatment group was analyzed. RESULTS: The SVR rate was
      higher in patients treated for 48 weeks than in those treated for 24 weeks (74.0%
      vs. 52.9%, P=0.028). In the multivariate analysis, age < 50 years, platelets > or
      = 150,000/mm(3), and treatment duration for 48 weeks remained significant
      independent predictors of SVR. Fourteen of the 24 patients who relapsed in the 24
      week treatment group received split 24-week therapy, and 6 patients (42.9%)
      achieved SVR. The overall SVR rate did not differ significantly between the 24
      week treatment group, including those who underwent 24-week split therapy
      (64.7%), and the 48-week treatment group (64.7% vs. 74%, P=0.311). CONCLUSIONS:
      The 24-week plus additional split 24-week therapy following failure is a useful
      treatment strategy for patients with genotype 1 CHC.

PMID- 20037269
TI  - [Two cases of toxic hepatitis caused by arrowroot juice].
AB  - Herbal remedies and health foods are widely used, and their side effects have
      been reported. We describe two cases of symptomatic toxic hepatitis that
      developed in middle-aged women after ingesting arrowroot juice. The clinical
      manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic
      hepatitis was made using the Roussel Uclaf Causality Assessment Method score on
      the basis of the patient's history and laboratory data. After supportive care,
      the patients showed rapid improvements of clinical symptoms, laboratory findings,
      and liver stiffness. Clinicians should be aware that the consumption of arrowroot
      juice can cause toxic hepatitis.

PMID- 20037270
TI  - [A case of primary hepatic epithelioid hemangioendothelioma with spontaneous
      rupture].
AB  - Primary hepatic epithelioid hemangioendothelioma is a rare neoplasm of
      endothelial origin. The clinical manifestations are nonspecific, ranging from
      complete absence of symptoms to hepatic failure and death. Spontaneous rupture of
      a hepatic epithelioid hemangioendothelioma is an extremely rare presentation. We
      present a case of primary hepatic epithelioid hemangioendothelioma in a 65-year
      old male patient with alcoholic liver cirrhosis. He was hospitalized due to
      epigastric pain and multiple liver masses on abdominal ultrasound. Dynamic liver
      CT imaging revealed multiple peripheral nodular enhanced mass lesions with
      delayed centripetal enhancement, and the adjacent collection of high-attenuation
      fluid along the liver capsule. Abdominal tapping revealed blood in the peritoneal
      cavity. Primary hepatic epithelioid hemangioendothelioma with spontaneous rupture
      was finally diagnosed based on a histopathologic examination revealing positive
      immunohistochemical staining for CD34.

PMID- 20037271
TI  - [A case of acute cholestatic hepatitis induced by Corydalis speciosa Max].
AB  - Herbs are widely used as treatments for various symptoms. However, several herbs
      have been reported to be inducers of liver injury. We report herein a case of
      hepatotoxicity induced by Corydalis speciosa Max. A 37-year-old male complained
      of jaundice and mild abdominal discomfort. A thorough history was taken, and
      laboratory investigation, diagnostic imaging studies, and percutaneous liver
      biopsy sampling were conducted to determine the cause of liver injury. An
      accurate cause was not revealed. We administered supportive management for acute
      cholestatic hepatitis of unknown origin, after which his symptoms disappeared and
      serum aminotransferase levels decreased gradually to near normal levels. However,
      at 2 months after discharge, the symptoms and the elevation of aminotransferase
      levels recurred. At that time he told us that he had repeatedly but
      unintentionally eaten a herb called "Hwang-geun cho"(Corydalis speciosa Max.).
      Thus, we diagnosed his case as herbal hepatotoxicity.

PMID- 20037272
TI  - [Intrahepatic cholangiocarcinoma associated with Clonorchis sinensis infection].

PMID- 20037273
TI  - [Neuroendocrine tumors of the liver].

PMID- 20037275
TI  - Current status of liver diseases in Korea: hepatitis B.
AB  - Hepatitis B virus (HBV) infection is the one of the most common causes of the
      liver diseases in Korea. Since the discovery of Australia antigen (hepatitis
      associated antigen, or HBsAg later), hepatitis associated antigen was tested
      widely. HBsAg was detected in 6.6-8.6% in 1980's. Later, it decreased to 5.7% in
      1990's. Remarkably, seropositivity of the children deceased to 0.2% after the
      nationwide vaccination program. Although hepatitis B vaccines are highly
      effective, the failure rate of perinatal prophylaxis in babies born to HBsAg
      positive mother was reported to be 4.25%. Treatment of chronic hepatitis B was
      initiated after the introduction of interferon alpha. Lamivudine opened a new era
      of oral antiviral agent, and it has been widely used in Korea since 1999.
      Adefovir was proven to have a good efficacy for lamivudine-resistant chronic
      hepatitis B. Newer potent antiviral agents such as entecavir, clevudine, and
      telbivudine are available currently. Further studies are warranted for
      understanding factors influencing natural history, improving treatment outcomes,
      and overcoming vaccine non-response.

PMID- 20037276
TI  - Current status of liver disease in Korea: hepatitis C.
AB  - Chronic hepatitis C (CHC) is the third most common cause of chronic liver disease
      and hepatocellular carcinoma (HCC) in Korea, following hepatitis B virus (HBV)
      infection and alcohol. HCV prevalence among Koreans older than 40 years of age
      has been estimated to be 1.29%. The prevalence of CHC increases with age, with
      the peak prevalence at the age of 60 or older. Blood transfusions have generated
      no risk of HCV infection since April 1991, when routine screening for anti-HCV in
      blood donors was adopted in Korea. Although injection drug use seems to be one of
      the most important risk factors of HCV infection among young adults in urban
      areas, the majority of CHC patients are not associated with injection drug use.
      Exposure to acupuncture was identified as a significant risk factor among older
      adults in rural areas. The mean age of patients with HCV-related cirrhosis and
      HCC was consistently about 10 years above that of patients associated with HBV.
      Genotypes 1b and 2a are the two most common types with almost equal proportions,
      and other genotypes are extremely rare. Korean patients with CHC have a high
      likelihood of responding to combination therapy with pegylated interferon and
      ribavirin, with a sustained virological response rate of 60-70% in patients with
      genotype 1 and 85-90% in those with genotype 2.

PMID- 20037277
TI  - Current status of liver diseases in Korea: toxic and alcoholic liver diseases.
AB  - The study of the epidemiology of toxic liver injury has been limited in Korea.
      The number of hospitalizations for toxic liver injury has been estimated to be
      2,400 persons per year. About 30~40% of fulminant hepatitis was attributed to
      toxic hepatitis. The frequent causative agents of toxic hepatitis in Korea are
      herbal medicines (34-40%), folk remedies (23-34%), and prescribed medicines (24
      55%). However, the most common agents causing severe liver injury including
      fulminant hepatitis are herbal medicine and folk remedies. Antituberculosis drugs
      and acetaminophen are two common causes of fulminant hepatitis among prescribed
      drugs. Alcohol is one of the leading causes of chronic liver disease in Korea. No
      nationwide study on the epidemiology of alcoholic liver disease (ALD) has been
      carried out, but 7-31% of cirrhosis has been reported to be alcoholic in a few
      single-center studies. Alcohol could be a risk factor for the development of
      hepatocellular carcinoma (HCC) in chronic viral hepatitis. Several studies have
      shown that alcohol increased the risk of HCC in liver cirrhosis with HBsAg or
      anti-HCV. Furthermore, alcoholic cirrhosis with occult hepatitis B virus
      infection increased the risk of HCC.

PMID- 20037278
TI  - Current status of liver disease in Korea: nonalcoholic fatty liver disease.
AB  - Recently, obesity (BMI>or=25 kg/m2) and type II diabetes mellitus have reached
      epidemic proportions in Korea, and rates of nonalcoholic fatty liver disease
      (NAFLD) are between 10% and 25% of the general population. NAFLD in Korea is as
      closely associated with several components of metabolic syndrome including,
      obesity, hypertension, diabetes and dyslipidemia as it is in Western countries.
      Insulin resistance and hyperinsulinemia may play a role in the pathogenesis of
      fatty liver in patients with normal body weight as well as in patients with
      obesity. And, obesity induced accumulation of fat in the adipose tissue leads to
      an imbalance in the regulation of adipokines, such as downregulation of
      adiponectin and upregulation of retinol-binding protein 4 (RBP4) and ghrelin.
      High BMI, the AST/ALT ratio, and ALT levels could be used to distinguish NASH
      from simple steatosis in Korean patients. In large number of NAFLD patients who
      underwent a voluntary medical checkup, even a small weight reduction was
      associated with improvements in their hepatic steatosis grade on ultrasonography,
      serum aminotransferase levels, and related metabolic abnormalities. Subjects with
      fatty liver disease should be advised to lose weight through lifestyle
      modifications. Small animal and human studies of treatment with PPAR agonists and
      betaine have been reported in the Korean literature. It is now acknowledged that
      NAFLD is the most common liver disease in Korea, largely due to the considerable
      increase in metabolic abnormalities such as obesity and diabetes. Future studies
      should continue to focus both on the pathogenesis and the treatment of NAFLD in
      order to accumulate more of our own data.

PMID- 20037279
TI  - Current status of liver diseases in Korea: liver cirrhosis.
AB  - Liver cirrhosis represents the final common pathway of virtually all chronic
      liver diseases, and is characterized by an accumulation of extracellular matrix
      rich in fibrillar collagens. Patients with cirrhosis are at risk of developing
      many potential complications. The most common complication seen in patients with
      liver cirrhosis is ascites, and the most lethal one is bleeding varices. Other
      intermediate and late stage complications include spontaneous bacterial
      peritonitis, hepatic encephalopathy, and hepatorenal syndrome. The mortality and
      morbidity attributable to liver disease in Korea have decreased continuously over
      the past decades, probably due to the implementation of universal vaccination and
      potent antiviral therapies. In addition, recent advances in the understanding of
      the pathophysiology of cirrhosis and in various management approaches to
      cirrhosis complications will contribute to the steady improvement in patient
      outcomes in this country. This review article outlines recent changes in
      etiologies and prognosis, and the advances in management of cirrhosis in Korea.

PMID- 20037280
TI  - Current status of liver diseases in Korea: hepatocellular carcinoma.
AB  - Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the
      third common leading cancer in Korea. During the last two decades, the incidence
      rate of primary liver cancer has shown a modest decrease, but its mortality rate
      has slightly increased. The incidence of HCC, according to age, peaks in the late
      sixth decade in men and in the early seventh decade in women. Hepatitis B virus
      (HBV) is the most important risk factor, which represents approximately 70% of
      all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major
      risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10
      years earlier than HCV-associated HCC due to a more prolonged exposure to HBV,
      which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic
      area. National Cancer Control Institute, which was reorganized in 2005, is now
      working for several national projects such as National Cancer Registration
      Program, National R&D Program for Cancer Control and National Cancer Screening
      Program. International collaboration for the clinico-epidemiologic research would
      be needed to provide the specific measures for managing HCC in diverse etiologic
      situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular
      carcinogenesis might be clarified to provide insights into the advanced
      therapeutic and preventive approaches for HCC in Korea, where the majority of HCC
      originate from chronic HBV and HCV infections.

PMID- 20037281
TI  - Current status of hepatic surgery in Korea.
AB  - Since the first liver resection was carried out in Korea in 1959, there have been
      remarkable changes in the field of surgery. With technical advancement and the
      improvement of perioperative care, liver resections are widely performed and
      surgical mortality is approaching zero. In the early 1990s, liver transplantation
      evolved as a feasible option in the treatment of end-stage liver disease in
      Korea, with successful adult living-donor liver transplantation (LDLT) as one of
      the greatest achievements. Various innovations in surgical approaches have been
      introduced. We review the current status of hepatic surgery in liver disease in
      Korea.

PMID- 20037282
TI  - Current status of liver diseases in Korea: hepatitis A.
AB  - The seroprevalence of anti-HAV (hepatitis A virus) has been decreasing in Korea.
      The decrease in HAV infection in young adults has resulted in the reduction of
      individuals with protective antibody and an increase in hepatitis A in the adult
      population. The increase in HAV infection in adults will have an impact on the
      magnitude and severity of the disease. In Korea, symptomatic hepatitis A has been
      gradually increasing since the mid-1990s, with a tendency toward an increase in
      mean age and disease severity. The endemic genotype of HAV in Korea has been
      changing from genotype IA alone to a mixture of genotype IA and IIIA. Therefore,
      preventive measures including universal vaccination in infants and active
      immunization of the adult population should be considered.

PMID- 20037283
TI  - Systemically circulating colitogenic memory CD4+T cells may be an ideal target
      for the treatment of inflammatory bowel diseases.
AB  - Inflammatory bowel diseases (IBD) are thought to be caused by a complex
      interaction of genetic, immunological, and environmental factors. Why is it that
      once an IBD develops it lasts a long time? Considering this simple question, we
      propose that coliotogenic memory CD4+T cells that remember the prototype of the
      disease in each patient are formed in IBD at the onset, and, perceiving them as
      "benign T-cell leukemia"-like lifelong memory CD4+T cells that hematogenously
      spread throughout the body, we thus propose that systemic circulating colitogenic
      memory CD4+T cells would be an ideal target for the treatment of IBD.
      Accordingly, selective depletion of colitogenic memory CD4+T cells by
      leukocytapheresis and blockade of circulation of colitogenic memory CD4+T cells
      by a newly developed immunosuppressant, FTY720, may be associated with dramatic
      efficacy and a marked reduction of inflammatory cytokines produced by activated
      leucocytes. We here describe the immunological pathogenesis focusing on the
      generation of circulating colitogenic memory CD4+T cells and the possible logics
      of leukocytapheresis and FTY720 for the treatment of IBD.

PMID- 20037284
TI  - Perspectives in medical education 8. Enhancing preclinical education in Japan
      with a clinically focused, interactive anatomy curriculum.
AB  - Reform of preclinical medical education in Japan requires changes in the
      curriculum to make it more clinically focused and interactive. At present, course
      content in Anatomy is usually designed and taught with little or no clinical
      direction and involves a heavy emphasis on by-rote learning to memorize often
      minor facts that have little importance in clinical medicine. As a result, the
      content is boring, it is learned solely for the purpose of passing exams and it
      is promptly forgotten, with little sense of its need in clinical practice.
      Successful reform of the curriculum in Anatomy requires two critical changes. The
      first is that content must be made interesting to students by emphasizing its
      clinical importance, through a close collaboration between preclinical and
      clinical departments, Thus, the Surgical Faculty must be incorporated in the
      organization and teaching of the Anatomy curriculum. Core content can thereby be
      pared down to only what is considered essential to provide a foundation for the
      later clinical years, and the clinical importance of that content will, in turn,
      be self-evident to students. The second change that must be implemented is to
      make the learning process more appealing to the students. This can be facilitated
      by the use of any of several commercial IT programs that make learning in Anatomy
      both dynamic and engaging. These dual strategies will considerably enhance the
      learning of one of the most basic subjects in the medical school and ensure that
      the review and retention of the material are enhanced.

PMID- 20037285
TI  - Value of genetic testing in the otological approach for sensorineural hearing
      loss.
AB  - Sensorineural hearing loss (SNHL) is one of the most common disabilities in
      human, and genetics is an important aspect for SNHL, especially in children. In
      recent 10 years, our knowledge in genetic causes of SNHL has made a significant
      advance, and now it is used for diagnosis and other clinical practices.
      Hereditary hearing loss can be classified into syndromic and nonsyndromic hearing
      loss. As the nonsyndromic deafness genes, more than 100 loci for deafness genes
      have been determined, and more than 40 genes were identified. Furthermore, more
      than 300 forms of syndromic hearing loss have been characterized, and each
      syndrome may have several causative genes. In childhood hearing loss, early
      educational intervention is required in addition to medical intervention for
      normal development of speech and language. In addition, even severe to profound
      hearing loss may be restored very effectively by hearing aids or cochlear
      implants. Because of these features of SNHL, genetic testing has exceptionally
      high value in the medical practice for hereditary hearing loss. Several
      strategies are used for genetic testing of SNHL for accurate and efficient
      identification of the genetic causes, and the results were used for explanation
      of the cause, prediction of auditory features, prevention of deafness, management
      of associated symptoms, determination of therapy, and genetic counseling.
      Identification of damaged cells in the inner ear and the underlying mechanism by
      genetic testing undoubtedly facilitates development and introduction of novel and
      specific therapies to distinct types of SNHL.

PMID- 20037286
TI  - Activities of daily living (ADL) structure of patients with Duchenne muscular
      dystrophy, including adults.
AB  - OBJECTIVE: To study the activities of daily living (ADL) structure of patients
      with Duchenne muscular dystrophy (DMD). DESIGN: Cross-sectional survey. SUBJECTS:
      Seventy-two patients with DMD (mean [SD] age, 17.2 [8.1] years), recruited in 160
      bed regional center for neuromuscular disease. methods: We assessed 72
      participants with the Functional Independence Measure (FIM SM), and determined
      the difficulty order of the FIM SM items with the percentage of patients who were
      independent (6 or 7) for each FIM item (% independence). RESULTS: The ADL of
      patients with DMD had an order in terms of difficulty. For the motor subscale,
      the most difficult item was stairs, and the easiest item was locomotion. On the
      cognitive subscale, problem solving was the most difficult item. When we compared
      item difficulty between patients <15 years of age and those > or =15 years, the %
      independence was lower in the older age group for all motor items. The decrease
      in the % independence of the eating item with age was significant; however
      bladder management was well maintained. CONCLUSIONS: ADL of patients with DMD has
      a specific difficulty order. The order of difficulty is based on the relative
      level of independence/dependence. The difficulty order was maintained, although
      the structure of ADL changed with age.

PMID- 20037287
TI  - Coronary re-implantation after completion of neo-aortic reconstruction in
      arterial switch operation: accurate intraoperative assessment for the optimal re
      implantation site.
AB  - The arterial switch operation (ASO) has evolved into the treatment of the choice
      for most forms of transposition of the great arteries (TGA). Despite advancement
      in the technical aspects of the procedure, certain anatomical variations of the
      coronary arteries are still considered as surgical risks. We have recently
      employed a novel technique for coronary artery reconstruction in ASO to achieve
      further improvement of coronary transfer in cases with complex coronary anatomy.
      The technical key of the procedure is that reconstruction of the coronary
      arteries is preceded by neo-aortic anastomosis. After neo-aortic reconstruction
      is accomplished, the neo-aorta is temporarily distended with removal of the cross
      clamp. The distended neo-aorta informs us its postsurgical geometry, which
      facilitates accurate assessment for the optimal site of coronary button transfer.
      The technique was feasible in 13 of 15 children who were consecutively treated by
      our group between 2003 a nd 2008. All patients recovered uneventfully and no
      coronary perfusion issue has occurred during the follow-up period. However, the
      complex anatomy of the coronary arteries in two children was not amenable to this
      technique. One with double loops (1RL; 2Cx) accompanied by side-by-side
      relationship of the great arteries underwent the open trapdoor technique, while
      the other with intramural coronary artery underwent the Imai method, that is one
      of procedure in which the coronary arteries are left in situ. The coronary re
      implantation after neo-aortic reconstruction is promising to minimize
      postsurgical coronary ischemia and suitable for most ASO cases. However, various
      modifications of coronary transfer are required in a few variations of the
      coronary anatomy and we have to pursue further technical refinement of coronary
      artery transfer in ASO.

PMID- 20037288
TI  - Fibroma of the omentum resembling an ovarian tumor in the pelvis.
AB  - We would like to report the case of a patient with fibroma of the omentum that
      resembled an ovarian tumor in the pelvis. Since primary tumours of the omentum
      are rare, there is a paucity of information about the biology of such tumors in
      the basic texts and literature. An ultrasound examination of the patient revealed
      a mass, likely of ovarian origin, which consisted of liquid and solid components.
      It was suspected to be a malignant ovarian tumor. However, laparotomy
      demonstrated it was an omental tumor. This case shows that it can be difficult to
      pre-operatively diagnose omental fibromas because of their close resemblance to
      ovarian tumors.

PMID- 20037289
TI  - [Mechanism of immunotherapy enhancement in cancer therapy by hyperthermia].
AB  - Although hyperthermia controls cancer alone, hyperthermia is more effective by
      using it together with chemotherapy and radiotherapy. In this study, we attempted
      to show that the effect of immunotherapy for cancer patients was remarkably
      enhanced by using hyperthermia.

PMID- 20037290
TI  - [Effect of practical use of preoperative immunonutrition with impact on
      prevention of postoperative pneumonia after esophagectomy].
AB  - To clarify the clinical benefits of administering immune-enhancing diet,
      Impact,we examined retrospectively the effect of preoperative immunonutrition
      with Impact on prevention of postoperative pneumonia after esophagectomy. In 47
      patients without preoperative radiotherapy, no patient who preoperatively
      administered Impact>or=2,250 mL failed to develop pneumonia. The patients whose
      postoperative hospital stay was more than 30 days were administered
      Impact<or=2,000 mL except for one case. These results suggest that even
      preoperative administration of less amount of Impact than an estimated maximum
      dose, depending on patients' condition, may be beneficial to prevent
      postoperative pneumonia and a long hospital stay after surgery.

PMID- 20037291
TI  - [A study of nutrition screening for patients with surgically treated esophageal
      cancer].
AB  - PURPOSE: The present study was performed to investigate the effects of the
      nutrition screening index and pulmonary function test data for patients who
      underwent surgery for esophageal cancer, based on the incidence of postoperative
      complications and the duration of postoperative hospitalization. SUBJECTS AND
      METHODS: A total of 69 patients who received esophageal cancer resection were
      included in the study. It was determined how the parameters studied (ie, between
      ages, concomitant diabetes mellitus, body mass index( BMI), serum albumin level,
      Onodera's prognostic nutritional index, percentage of vital capacity(%VC), and
      forced expiratory volume[ FEV]1.0%) were related to the incidence of
      complications and the duration of postoperative hospital days, as expressed by
      the median days for all patients and the frequency of long-term hospitalization.
      RESULTS: The incidence of postoperative complications was significantly higher in
      patients aged 65 and above and those with a %VC value of less than 80%. The
      median duration of postoperative hospitalization was longer in those aged 65 and
      above and those with a FEV1.0% value of less than 70%, which was related to BMI.
      In addition, the frequency of long-term hospitalization was higher in those aged
      65 and above, which was also related to BMI. CONCLUSIONS: The results of the
      present study confirm that postoperative complications and length of
      postoperative hospital stay in patients with surgically treated esophageal cancer
      were largely dependent on their pulmonary function as well as age and BMI used
      for the nutrition screening index. Nutrition screening combined with pulmonary
      function tests, using age, BMI, %VC, and FEV1.0%, is considered desirable to
      avoid postoperative complications associated with esophageal cancer.

PMID- 20037292
TI  - [Dendritic cell vaccine for intrahepatic cholangio cellular carcinoma--a study of
      relationship between immuno-reaction and clinical outcome].
AB  - The clinical outcome of intra-hepatic cholangiocelluler carcinoma (ICC) is very
      poor. To prevent a tumor relapse after curative operation, we employed the
      combination therapy of adaptive transfer of anti-CD3 activated T cells and
      dendritic cell vaccine therapy (DC-CAT therapy) since 2000. During DC-CAT
      therapy, about a half of patient revealed skin reaction positive. Moreover, the
      patient who had a skin reaction showed a significantly good clinical outcome. In
      this study, we investigated the difference between skin reaction positive and
      negative checking with the surface markers of T cells. The patient who had skin
      reaction positive increased the number of lymphocyte. Especially, CD8 positive T
      cells were increased about 2 folds in number before the DC-CAT therapy, and
      decreased Foxp3 positive regulatory T cells. Our data suggest that increasing
      cytotoxic T cells and decreasing regulatory T cells made the difference of the
      clinical outcome such as a disease free survival rate and overall survival rate
      after curative operation for ICC patient.

PMID- 20037293
TI  - [Ten cases of advanced gastro-intestinal cancer that required preoperative dosage
      of PSK].
AB  - We examined ten convalescent cases of local progression digestive organ cancer,
      which required a radical operation after a 2-week administration of preoperative
      dosage of PSK. Because adjuvant chemotherapy was performed for all of the cases,
      3 out of 5 advanced gastric cancer patients and 4 out of 5 advanced colorectal
      cancer patients had more than 5-year survival. We might be effective in
      controlling a host immune compromise for the lap art period, which was our aim,
      how long preoperative PSK dosage has contributed for the extension of survival
      duration. We also examined the influence of the dosage in this study in
      preoperational of PSK, which gave a host immune compromise by the operational
      aggression so far, and we reported it as well.

PMID- 20037294
TI  - [Impacts of PSK and TbetaR inhibitor on immune response in immunosuppressive
      status associated with cancer].
AB  - Secretion of the transforming growth factor-beta (TGF-beta) by tumor cells
      suppresses an antitumor immune response in which dendritic cells (DCs) play an
      important role to activate cytotoxic T lymphocytes (CTLs). Here we report that
      small molecule TGF-beta signaling inhibitor, SB-431542, induces DC maturation in
      vitro when combined with protein-bound polysaccharide K (PSK). PSK has been used
      clinically as an anti-tumor agent in Japan. In this study, we examined the impact
      of PSK and SB-431542 on maturation of DCs under immunological tolerant status. At
      first, we added SB and PSK to cultures of human DCs generated from peripheral
      monocytes in the presence of TGF-beta and examined expression of CD83, production
      of Interleukin-12 (IL-12) and capacity of DCs to induce T cell proliferation. SB
      431542 with PSK induced up regulation of CD83 expression of DCs and improved
      their abilities to produce IL-12. They also augmented the capacity of DCs to
      activate naive T cells in allogeneic mixed lymphocyte reaction. These results
      suggested that PSK with TGF-beta receptor I kinase inhibitor should be able to
      induce antitumor immune response in immune-tolerant patients associated with TGF
      beta activity.

PMID- 20037295
TI  - [PSK-mediated growth suppression and enhancement of 5-FU/docetaxel-induced
      cytotoxicity in human esophageal cancer cell lines].
AB  - PSK, a protein-bound polysaccharide, is widely used for treating cancer patients
      as an immunostimulant. However, its direct action on cancer cells is not fully
      understood. In the present study, we investigated direct effects of PSK alone or
      in combination with 5-FU, CDDP and docetaxel on tumor growth by using esophageal
      cancer cell lines, KYSE170 and TE13. Cells were incubated with different
      concentrations of PSK for 72 hour, and cell viability was determined by WST-8
      assay, and cell cycle was analyzed by flow cytometry. As a result, PSK of 100
      microg/mL induced growth suppression dose-dependently in the both cell lines, and
      flow cytometric analysis showed a PSK dose-dependent increase of sub-G1 cells
      indicating apoptotic cells. In addition, when cells were incubated with different
      concentrations of 5-FU and docetaxel in the presence of PSK at the dose of 5
      microg/mL showing no growth suppression, cytotoxicity induced by 5-FU and
      docetaxel was significantly enhanced. These results indicate that PSK not only
      shows tumor growth suppression by apoptosis induction, but also enhances 5-FU and
      docetaxel-induced cytotoxicity.

PMID- 20037296
TI  - [Administration of polysaccharide K (PSK) for stage III rectal cancer in clinical
      practice].
AB  - This retrospective study was performed to examine the frequency of PSK
      administration in patients with Stage III rectal cancer in clinical practice, and
      the effect of PSK on patient outcome. The subjects were 71 patients with Stage
      III rectal cancer who received postoperative adjuvant chemotherapy comprising
      fluoropyrimidines between April 1997 and March 2006. The frequency of PSK
      administration and factors affecting recurrence, disease-free survival, and
      overall survival were examined. The frequency of concomitant use of PSK with
      fluoropyrimidines was 79% (56 patients). Among the patients who were given PSK,
      the frequency of concomitant use of UFT alone was higher in Stage III a patients,
      while the rate of concomitant use of fluoropyrimidines and Leucovorin was higher
      in Stage III b patients (p<0.01). Multivariate analyses revealed that the only
      predictive factor affecting recurrence, disease-free survival, and overall
      survival was Stage III b. Although the rate of concomitant use of PSK in adjuvant
      chemotherapy for patients with Stage III rectal cancer was high, we did not
      evaluate the effect of PSK because there was a marked bias in relation to the
      subclassification of Stage III disease and the use of Leucovorin in these
      subjects. Prospective randomized trials with stratification of Stage III disease
      will be needed in the future to validate the efficacy of PSK.

PMID- 20037297
TI  - [The IL-6 and COX-2 expression related to sensitivity of chemoradiotherapy and
      prognosis in esophageal carcinoma].
AB  - Chemoradiation therapy (CRT) for esophageal cancer induces inflammatory responses
      within tumor tissues. Inflammatory cells infiltrated into the tumor tissues may
      modulate the CRT responses via inflammation-related molecules such as IL-6 or COX
      2. In the present study, we investigated a relationship between IL-6/COX-2
      expression and CRT responses for esophageal cancer. A surgical resection
      following CRT was performed, and the specimens from the patients with cT3/T4
      esophageal squamous cell examined for IL-6/COX-2 expression in both residual
      cancer and stromal cells by immunohistochemical staining. CRT responses were
      divided into responder group (Grade 1b and Grade 2) and non-responder group
      (Grade 1a). COX-2 in cancer cells and IL-6 in stromal cells were associated with
      non-responder and responder, respectively. In addition, IL-6 in stromal cells was
      significantly correlated with overall survival. Our data suggest that
      inflammatory responses concomitant with CRT responses could play a role in
      chemoradiation responses and prognosis.

PMID- 20037298
TI  - [Current trends and problems in chemotherapy for elderly patients with advanced
      gastric cancer].
AB  - PURPOSE: To assess current trends and problems in chemotherapy for elderly
      patients with unresectable gastric cancer. PATIENTS AND METHODS: Patients with
      unresectable gastric cancer were divided into two groups: an elderly group aged
      70 years or older (n=28), and a control group aged younger than 70 years (n=46).
      The feasibility, safety, and efficacy of chemotherapy were compared between the
      two groups. The induction rate for a first-line treatment did not differ between
      the groups (89% for the elderly group versus 93% for the control group). A
      regimen comprising S-1 and cisplatinum (CDDP) was selected most frequently as the
      first-line treatment in both groups. When an analysis was restricted to patients
      given S-1 and CDDP, the elderly group showed fewer cycles of CDDP administration,
      a higher rate of grade 3 or worse adverse events, a lower rate of switching to a
      second-line treatment, and a shorter overall survival than the control group,
      although the p values did not reach a significant level. Among patients aged 70
      years or more, those given S-1 alone showed an overall survival equivalent to
      that for patients given S-1 and CDDP. In conclusion, in clinical practice, it
      seems appropriate to consider whether the S-1+CDDP regimen is the most optimal
      first-line treatment for elderly patients with gastric cancer.

PMID- 20037299
TI  - [The prognosis of patients with an allergic reaction in the treatment of mFOLFOX6
      therapy].
AB  - We examined 155 patients who received a first-line modified FOLFOX6 ( mFOLFOX6)
      regimen for unresectable or recurrent colorectal cancer regarding oxaliplatin
      related allergic reactions and prognosis of patients who developed such allergic
      reactions. Twenty eight patients (18.1%) developed a total of 44 allergic
      reactions (2.9%): The first allergic reactions were grade 1 in nine, grade 2 in
      seventeen, and grade 3 in two. The median number of cycles of mFOLFOX6 until the
      first allergic reaction was 8.5 (range, 1-25). Compared with non-allergic group
      patients (n=127), allergic group patients (n=28) had mFOLFOX6 regimen more
      frequently (p=0.01) and higher rate of introduction to second-line FOLFIRI
      regimen (p<0.01). When analysis was restricted to patients who were given a
      second-line FOLFIRI regimen, the response rate and disease control rate
      associated with FOLFIRI treatment did not differ significantly between the two
      groups. However, the allergic group patients tended to show longer disease-free
      survival (p=0.16) and showed longer overall survival after the start of second
      line treatment (p=0.03). In addition, the allergic group patients showed a longer
      overall survival after the start of mFOLFOX6 (p=0.03). These results suggest that
      allergic reactions in the first-line mFOLFOX6 treatment might not be a poor
      prognostic factor, considering the efficacy of second-line FOLFIRI regimen.

PMID- 20037300
TI  - [The case of tumor escape mechanism by changing their tumor-associated antigens].
AB  - A 53-year-old woman presented with a diagnosis of advanced gallbladder cancer at
      our hospital. She was evaluated with CT scan and given a diagnosis of Stage IVb
      due to the multiple lymph nodes metastases and significant invasion to the
      artery. However, we underwent simple cholecystectomy followed by immunotherapy
      that was the hope of herself and her family. The serum level of DUPAN-2 was
      gradually elevated to 6,800 U/mL, and the metastases to the liver were detected.
      After we started the dendritic cell vaccine pulsed with autologous tumor-lysate
      with S-1, DUPAN-2 decreased to 980 U/ mL. The CT scan showed complete response
      (CR) in the liver metastases and partial response (PR) in the lymph node
      metastases. However, the serum level of CEA elevated since the MUC-1 peptide was
      used instead of autologous tumor- lysate, even DUPAN-2 did not. The liver
      metastases were in control, but the lymph nodes metastases had progressed. She
      died of the progressed lesion later in approximately one year from the operation.
      This case demonstrated a possibility of the tumor escape mechanism by changing
      their tumor-associated antigens.

PMID- 20037301
TI  - [Indoleamine 2,3-dioxygenase activity during chemotherapy in patients with breast
      cancer].
AB  - We evaluated the significance of indoleamine 2, 3-dioxygenase (IDO) in recurrent
      breast cancer during chemotherapy. IDO activity can be measured by tryptophan
      (Trp)/kynurenine (Kyn) ratio. Trp and Kyn were measured by high performance
      liquid chromatography (HPLC). The correlations among age and Trp/Kyn ratio or
      immunosuppressive acidic protein (IAP) value in pre-chemotherapies or post
      chemotherapies were studied. In under 35-year-old patients, there were no
      correlations between pre-chemotherapy and post-chemotherapy in IAP values and
      Trp/Kyn ratio. But in over 36-year-old patients, both Trp/Kyn ratio and IAP value
      in post-chemotherapy were higher than in pre-chemotherapy. These results suggest
      that the immunological damages for the patients during chemotherapy may depend on
      the age of patients.

PMID- 20037302
TI  - [The combined effect of paclitaxel and toremifene therapy for metastatic breast
      cancer].
AB  - A comparison of paclitaxel (PTX) alone with PTX+toremifene (TOR) in hormone
      receptor negative metastatic breast cancer (MBC) patients was conducted to
      determine the therapeutic value of adding TOR to a PTX regimen. Eight MBC
      patients received 80 mg/m2 PTX weekly (PTX group) and six MBC patients received
      the same weekly dose of PTX plus 120 mg/day TOR daily (PTX+TOR group). Patients
      were repeatedly treated with a combination of PTX and TOR as long as a disease
      progression or unmanageable severe adverse events were defined. The PTX group was
      compared with the PTX+TOR group with respect to best overall response, response
      rate, clinical benefit rate, time to progression, adverse events and toxic
      profile of PTX and TOR. No significant difference in response rate was observed
      between the PTX group and the PTX+TOR group. However, a clinical benefit rate and
      time to progression improved significantly in the PTX+TOR group in comparison
      with the PTX group. TOR did not significantly enhance the adverse events of PTX.
      These results suggested that the combined treatment of PTX and TOR for MBC
      patients improved a patient response over PTX alone.

PMID- 20037303
TI  - [Concurrent chemoradiotherapy with nedaplatin and 5-fluorouracil (5-fu) for
      locally advanced squamous cell carcinoma of the esophagus].
AB  - BACKGROUND: Concurrent chemoradiotherapy (CRT) using cisplatin (CDDP) and 5
      fluorouracil (5-FU) is the standard treatment for unresectable locally advanced
      esophageal carcinoma. Although this regimen has been widely accepted in Japan,
      the adverse effect of CDDP such as gastrointestinal and renal toxicity may
      sometimes be the cause of interruption of the treatment, especially among the
      elderly patients. Cis-diammine-glycolatoplatinum(nedaplatin: CDGP) is a new
      platinum agent, which was developed with the aim of decreasing renal and
      gastrointestinal toxicities but maintaining the effectiveness of CDDP. We
      reported the efficacy and safety of CRT using CDGP and 5-FU for locally advanced
      squamous cell carcinoma of the esopahagus. PATIENTS AND METHODS: Between January
      2001 and December 2007, 65 patients with locally advanced esophageal cancer( 39
      patients with unresectable tumor( cT4) and 26 patients with distant lymph node or
      bulkey lymph node metastasis) were eligible and given informed consent and cared
      by the Department of Surgical Oncology of Osaka City University. Patients
      received a continuous infusion of 5-FU (250 mg/body) on days 1-21. CDGP was
      administered at the dose of 10 mg/body by bolus infusion for 1 hour on days 1-5,
      8-12 and 15-19 just before radiotherapy. Radiotherapy was delivered in 1.8 Gy
      fractions, 5 days/week for 4 weeks. For the effective cases of CRT, a surgical
      resection was followed subsequently and an additional radiotherapy at the dose of
      20 Gy was performed for non-effective cases. RESULTS: Complete or partial
      response was achieved in 46 patients (71%). Hematologic toxicities such as grades
      3 and 4 leucocytopenia developed in 19 patients and thrombocytopenia developed in
      20 patients, which were well tolerated by conservative therapy. Gastrointestinal
      and renal toxicities were developed in only a few patients. There was no CRT
      related death. Of all 65 patients, 25 patients underwent a surgical resection
      while 19 patients could receive a curative resection( R0 operation). In the
      resected cases, a 5-year survival rate and the median survival time were 27% and
      22.5 months, respectively. CONCLUSION: Concurrent CRT with CDGP and 5-FU was
      effective and safe for locally advanced squamous cell carcinoma of the esophagus.

PMID- 20037304
TI  - [Outcome of therapy for type 4 gastric cancer with peritoneal metastasis-
      diagnosis by laparoscopy and effect of chemotherapy].
AB  - Laparoscopy (st-lap) was performed for type 4 advanced gastric cancer cases, and
      chemotherapy was performed for P1 or CY1[ P(+)] cases. We present the results
      here. SUBJECTS: The subjects were type 4 advanced gastric cancer cases from
      October 2002 to December 2007 who underwent st-lap, as well as 7 P0 and CY0 [P(
      )] cases (the operative group), and 18 P(+) cases which underwent chemotherapy
      (the chemotherapy group). The administration of S-1 (80 mg/m2: days 1-14)+PTX
      (120 mg/m2: day 1) every 3 weeks was the basic regimen of chemotherapy. RESULTS:
      After 5- course of chemotherapy, st-lap was performed in 11-PR case(61%) and 4-SD
      case, in which clinical symptoms had improved. An operation was performed for 11
      P(-) case. Overall, there was 8-P(-) case(44%). The 1-and 3-year survival rates
      in the chemotherapy group in the 11 cases for which an operation was performed
      were 82 and 36%, respectively, and the 7 non-operative cases were 57 and 14%,
      respectively. Although there were no significant differences, the outcome was
      more favorable in the operative group. The 1-and 2-year survival rates in the
      operative and chemotherapy groups were 72, 39, 51 and 34%, respectively, and
      there was no significant difference. DISCUSSION: It was suggested that in cases
      of type 4 advanced gastric cancer, chemotherapy was necessary not only in P(+)
      but also in P(-) cases. Further investigation regarding the necessity of
      resection and choice of therapeutic regimen is required.

PMID- 20037305
TI  - [Results of neo-adjuvant chemotherapy by FOLFOX and FOLFIRI for colorectal liver
      metastasis].
AB  - We analyzed a treatment outcome and the effect of FOLFOX and FOLFIRI neo-adjuvant
      chemotherapy (NAC) for patient with liver metastasis of colorectal cancer. Eleven
      patients undergoing hepatectomy after NAC were investigated. FOLFOX was performed
      for 8 patients, and FOLFIRI was for 3 patients. The response rate was 45.5% (PR
      5, SD 6), and the reduction rate was 37.7%. The average ICG R15 value before
      hepatectomy was 13.7%. A complication during and after operations was not
      recognized. The average observation period was 19.8 months (8-45 months). Now, 9
      patients are alive with no recurrence. NAC by FOLFOX for liver metastasis of
      colorectal cancer showed a high reduction rate, and there was a little influence
      to hepatectomy indicating that FOLFOX could be an effective therapy.

PMID- 20037306
TI  - [Preoperative chemoradiotherapy for resectable lower rectal cancer].
AB  - To suppress local recurrence and preserve sphincter function, we performed
      preoperative chemoradiotherapy( CRT) of rectal cancer. Sixteen patients with
      lower advanced rectal cancer received tegafur/uracil/calcium folinate+RT followed
      by curative resection with lateral lymph node dissection 2-8 weeks later. The
      male/female ratio was found to be 11:5 (41-75 years old) and the CRT was feasible
      for all patients. There were 11-PR and 5-SD according to RECIST criteria, and
      lower isotope accumulation was observed for all primary tumors in FDG-PET study.
      After CRT, all patients received R0 curative resection (11 APR, 2 LAR, 1 Hartmann
      and 1 ISR). On pathological study, 3 patients showed complete response. Surgical
      complications including pelvic infection, delayed a wound healing and deep venous
      thrombosis, etc. In conclusion, preoperative CRT of advanced rectal cancer could
      potentially be useful for local control and sphincter saving, however, it is
      necessary to manage specific surgical complications due to radiation.

PMID- 20037307
TI  - [The possibility of local control of cancer by neoadjuvant chemoradiation therapy
      with gemcitabine and surgical resection for advanced cholangiocarcinoma].
AB  - Surgical resection is the gold standard of treatment for cholangiocarcinoma.
      However, there are also many recurrences after operation, because of the
      anatomical background and the tendency of invasion. We thought that eliminating
      the remnant of the cancer could yield a better prognosis. Therefore, an
      introduction of the neoadjuvant chemoradiation therapy with gemcitabine and
      surgical resection for advanced cholangiocarcinoma patient (NACRAC) was planned.
      The safety of NACRAC was confirmed by a pilot study. The recommended dose of
      gemcitabine (600 mg/m2) was determined by a phase I study. A phase II study is
      now being performed for evaluating the effectiveness and safety. NACRAC may
      control the frontal part of the tumor with difficult distinctions made by MDCT,
      and abolishing the cancer remnant is expected. The possibility of extended
      prognosis by NACRAC can be considered.

PMID- 20037308
TI  - [Estimation of preoperative induction chemoradiotherapy effectiveness for non
      small-cell lung cancer].
AB  - We have performed the clinical evaluations of preoperative induction
      chemoradiotherapy (CRTx) for 25 patients with non small-cell lung cancer (male:
      19, female: 6, mean age: 66.4-year-old). The clinical stages of these patients
      were IIA: 1, IIB: 7, IIIA: 14, and IIIB: 3, respectively. In the histological
      type of lung cancer, there were 12 patients of adenocarcinoma, 7 of squamous cell
      carcinoma, 1 of adenosquamous carcinoma, 1 of anaplastic carcinoma, and 4 of
      large cell carcinoma. We applied two courses of regimen as the pre-operative
      chemotherapy (CDDP+DOC or CBDCA+PTX). Twenty-four patients received radiotherapy
      as the concurrent radiotherapy (44 Gy: 22 patients, 60 Gy: 2 patients). Among the
      25 patients, 16 patients accomplished both chemotherapies, and the effects of the
      treatment were as follows: CR; none, PR; 15, SD; 9, respectively. And the other
      patient was not an evaluable case due to atelectasis. Histopathological effects
      (Ef) were Ef-3: 3, Ef-2: 11, Ef-1: 7, Ef-0: 1 and Ef was not evaluable in 3
      cases. Post operative pathological findings showed that 14 patients were down
      staged. There were no operative mortality associated with the operation, and no
      serious morbidity case was observed. Eighteen patients were survived and 1
      patient was survived with tumor metastases. Only one patient died of recurrence
      in the upper mediastinal lymph nodes, 3 patients died of the brain metastases,
      one died of hepatic metastasis, and one died of cryptogenic sudden death. As a
      result, there was no serious operative morbidity observed in the course of this
      CRTx. We therefore recommend that induction chemoradiotherapy as a beneficial pre
      operative treatment.

PMID- 20037309
TI  - [Evaluation of hepatic resection for synchronous liver metastasis from gastric
      cancer].
AB  - To evaluate the effect of hepatic resection for synchronous liver metastasis from
      gastric cancer, the clinicopathological factors of gastric cancer, the size and
      number of liver metastasis and surgical procedures for liver metastasis were
      studied. Between 1977 and 2006, a total of 49 patients (38 men and 11 women)
      underwent hepatic resections and gastrectomy. The median age was 70 years old
      (range 41-81). As for pathological type, intestinal/diffuse was 26/23.
      T1/T2/T3/T4 was 4/14/23/8. For lymph node metastasis, N0/N1/N2/N3 was 4/15/18/12.
      The number of liver metastasis: 27 patients had 1 lesion, 9 patients had 2
      lesions, and 13 patients had more than 3 lesions. A partial resection was
      performed for 37 patients. MST was 663 days. The 5-year survival rate was 19.7%.
      Univariate analysis pointed out several prognostic factors such as histological
      type of primary lesion, T-factor, lymph node metastasis, the number and size of
      liver metastasis and the procedures for hepatic resection. Multivariate analysis
      revealed that two factors of N0 or N1 in lymph node metastasis and partial
      resection of liver metastasis were favorable independent prognostic factors
      (p=0.0108 and p=0.0192). In conclusion, N0 and N1 state and partial resection of
      the liver metastasis would be good candidates for gastrectomy and synchronous
      resection of liver metastatic lesions.

PMID- 20037310
TI  - [Evaluation of hepatic arterial infusion chemotherapy for liver metastasis from
      gastric cancer].
AB  - We performed hepatic arterial infusion (HAI) chemotherapy for 11 patients with
      liver metastasis from gastric cancer, who had no other metastasis. The main
      antineoplastic drug was 5-fluorouracil (5-FU). The catheter was inserted into the
      hepatic artery using the GDA coiling method by interventional radiologic
      technique in 9 patients, and by operative treatment in 2 patients. The response
      rate for 10 patients was 91% (CR 3, PR 7, PD 1). The survival time from the
      beginning of the HAI chemotherapy was 8-34 months. The causes of withdrawal from
      the chemotherapy were PD in 7 patients and catheter troubles in 4 patients. There
      was no patient suffering from severe adverse effect. The HAI chemotherapy was
      effective and useful for patients with liver metastasis of gastric cancer. We
      thought a gastric cancer patient with liver metastasis who didn't have an
      uncontrollable other organ metastasis was a good target for this regimen.

PMID- 20037311
TI  - [The safety and efficacy of neoadjuvant chemotherapy for patients with hepatic
      colorectal cancer metastases].
AB  - The aim of this study is to investigate the safety and efficacy of neoadjuvant
      chemotherapy for patients with hepatic colorectal cancer metastases who underwent
      hepatic resection. Surgical complications and survival rates of the patients
      with/without neoadjuvant chemotherapy were analyzed. Neoadjuvant chemotherapy was
      not associated with sever surgical complications after hepatic resection.
      Postoperative survival rate of the patients with neoadjuvant chemotherapy was not
      superior to that of patients without neoadjuvant chemotherapy. Neoadjuvant
      chemotherapy for patients with hepatic colorectal cancer metastases who underwent
      hepatic resection is safe, but further studies are required to clarify its
      efficacy.

PMID- 20037312
TI  - [Predictive factors for histopathological liver injury in the patients who
      received preoperative systemic chemotherapy for colorectal liver metastases].
AB  - The operation for liver metastases from colorectal cancer is increasing due to a
      progress of chemotherapy. On the other hand, the live damage induced by
      chemotherapy affects on post operative course. We studied histopathological liver
      injury on the patients who received preoperative chemotherapy. Between January
      2004 and May 2009, forty seven patients underwent hepatectomy for colorectal
      liver metastases after systemic chemotherapy, and the remnant liver was
      histopathologically investigated about sinusoidal dilatation and non-alcoholic
      steatohepatitis. As a result, chemotherapy including irinotecan or oxaliplatin
      was significantly associated with sinusoidal dilatation, and female gender or
      higher body mass index was correlated with non-alcoholic steatohepatitis. These
      results should be taken into consideration before liver resection in patients who
      have received preoperative chemotherapy.

PMID- 20037313
TI  - [Hepatic metastatectomy of colorectal cancer following mFOLFOX6 treatment-
      analysis of 7 cases].
AB  - This retrospective study was performed to examine the outcomes of patients with
      liver metastasis of colorectal cancer, who received mFOLFOX6 regimen prior to
      hepatic metastatectomy. The reasons for introducing mFOLFOX6 prior to hepatectomy
      were unresectable hepatic lesions in two patients, presence or suspicion of
      extrahepatic lesions in four patients, and patient's refusal for hepatectomy in
      one patient. The mean number of cycles of administering mFOLFOX6 was 12.7 (range
      10-18), two patients received additional FOLFIRI regimen after mFOLFOX6
      treatment. The therapeutic efficacy revealed complete response in two, partial
      response in two, and stable disease in two by RECIST criteria. Histological
      examination revealed that six from 15 resected nodules were classified into grade
      3. Histological examination of the non-cancerous liver tissue revealed stage I
      sinusoidal dilation (Rubbia-Brandt's classification) in five and grade 1
      steatohepatitis (Brunt's classification) in two who received additional FOLFIRI
      regimen. Blood loss and duration of surgery of the subjects were identical to
      those (n=17) who underwent hepatic metastatectomy without preoperative
      chemotherapy during the same study period. It does not seem easy to determine the
      optimal timing of hepatic metastatectomy after FOLFOX treatment in clinical
      practice. However, our results suggest that preoperative FOLFOX treatment may
      have little adverse impact on the safety of hepatic metastatectomy.

PMID- 20037314
TI  - [Usefulness of hepatic arterial infusion chemotherapy for the patients with
      synchronous liver metastases from colorectal cancer].
AB  - We analyzed the results of hepatic arterial infusion chemotherapy (HAIC) for 24
      patients with synchronous liver metastases from colorectal cancer for the last
      twelve years in order to investigate the usefulness of HAIC for those patients.
      In 8 cases with resection of liver metastases, the median survival time (MST) was
      45 months, mean survival time was 53 months and a 5-year survival rate was 44%.
      In 16 cases without resection of liver metastases, 2 cases had complete response
      (CR), 10 cases had partial response (PR), 4 cases had stable disease (SD), and
      the response rate was 75%. There was a significant difference in the survival
      time of each response. MST was 25 months, and mean survival time was 38 months.
      According to the usefulness of HAIC for the patients with synchronous liver
      metastases from colorectal cancer, it seems that HAIC with effective general
      chemotherapy will have better results than HAIC.

PMID- 20037315
TI  - [Switching to direct intrahepatic arterial infusion of 5-FU after a progression
      of liver metastases from colorectal carcinoma treated with systemic infusion of
      FOLFOX].
AB  - Direct intrahepatic arterial infusion of 5-FU produced a significantly higher
      response rate than systemic infusion of FOLFOX in the treatment of hepatic
      metastases from colorectal carcinoma. Fourteen patients switched over from
      systemic FOLFOX therapy to intrahepatic protracted 5-FU infusion after a
      progression of liver metastases treated with systemic therapy. Of the 14 patients
      whose tumors had initially failed to respond to systemic FOLFOX therapy, 12 (85%)
      had a partial response, and 13 (93%) had a reduction in their tumor marker (CEA,
      CA19-9, TPA) when the treatment was switched to intrahepatic 5-FU therapy.
      Traditional chemotherapy toxicity, such as myelosuppression, nausea, vomiting and
      neurotoxicity did not occur in the intrahepatic group. Three out of 14 patients
      survived more than a year, and the longest was 18 months. A better survival rate
      can be achieved with the use of hepatic artery infusion therapy.

PMID- 20037316
TI  - [Therapeutic results of hepatic resection using thermal ablation for unresectable
      colorectal liver metastases].
AB  - We have retrospectively reviewed the therapeutic results of hepatic resection
      with or without thermal ablation therapy (TA) for colorectal liver metastases in
      138 patients between 1994 and 2006. A total of 88 unresectable liver metastatic
      lesions were selectively treated with TA as initial treatment (42 patients)
      basically in combination with hepatectomy. Overall, TA achieved a high local
      tumor control rate of 94.3%. Multivariate analysis revealed that initial TA
      therapy was not a significantly predictive factor of hepatic recurrence or any
      recurrence. TA therapies in combination with hepatectomy may offer improving
      resectability without risk to intrahepatic dissemination or to extrahepatic
      recurrence.

PMID- 20037317
TI  - [Evaluation of local coagulation therapy with hepatectomy for liver metastases].
AB  - Hepatectomy is accepted as the standard therapy in patients with resectable liver
      metastases. In recent years, the techniques such as microwave coagulation therapy
      (MCT) and radiofrequency ablation therapy (RFA) have been developed, so we have
      many options to treat. We evaluated nineteen subjects with cases of liver
      metastases who underwent thermoablative procedures with or without hepatectomy.
      RFA and MCT were used in 6 cases and 2 cases, respectively. In other 11 cases,
      they received a combined therapy: RFA+hepatectomy in 5 cases, and MCT+hepatectomy
      in 6 cases. Thermoablative therapy was used for 39 metastatic tumors. The mean
      tumor size was 13.7 mm, and a local recurrence was observed in 8 nodules (21%).
      No significant differences were observed in DFS and OS between thermoablative
      therapy and hepatectomy. Many patients with liver metastases received a repeated
      treatment, so we have to care about the remnant liver function. We conclude that
      thermoablative therapy with hepatectomy seems to be a less invasive procedure and
      effective therapy.

PMID- 20037318
TI  - [A case of chemo-radiation therapy with high degree of efficacy for esophageal
      cancer with liver metastasis].
AB  - A 78-year-old man underwent a radical resection for esophageal cancer (Stage III)
      and cardiac gastric cancer (Stage IA) at another hospital 2 years ago. After the
      operation, he was followed at that hospital. In 2008, abdominal CT scan and FDG
      PET/CT revealed a liver tumor. He was referred to our hospital and was diagnosed
      as esophageal cancer with liver metastasis. He received chemo-radiation therapy
      (CRT). The regimen was docetaxel hydrate (30 mg/m2, day 1, 8, 29 and 36) and S-1
      (60 mg/m2, day 1-14 and day 29-45) with radiation (45 Gy) for liver metastasis.
      He finished the CRT without any hematotoxicity, liver disorder and non
      hematotoxic adverse event (grade 3). Abdominal CT was done 2 months after the end
      of CRT and revealed that the tumor lesion disappeared completely. The patient is
      alive for 11 months after the CRT without any evidence of recurrence. The tumor
      disappeared completely for the last 11 months. We conclude that CRT is safe and
      very effective for esophageal cancer with liver metastasis.

PMID- 20037319
TI  - [A case of multiple liver and celiac lymph node metastases after curative
      esophagectomy for esophageal cancer successfully treated with hepatic arterial
      infusion and radiation therapy].
AB  - A 65-year-old woman, who had been operated by subtotal esophagectomy for
      esophageal cancer, was diagnosed as multiple liver metastases and celiac lymph
      node metastases one year after operation. The response evaluation revealed
      progressive disease after she had been suffering from nausea and anorexia
      throughout 2 courses of FP therapy. She refused to continue any more systemic
      chemotherapy, so we proposed an alternative to her, hepatic arterial infusion
      chemotherapy (HAI) for multiple liver metastases and radiation therapy for celiac
      LN metastases. Despite the marked reduction of all target lesions and maintenance
      of tumor marker level below the normal limits after 50 Gy of irradiation and 5
      courses of HAI, a novel solitary tumor had appeared in S3 of the liver and an
      abdominal pain during HAI had occurred at the end of 5th course of HAI. The
      angiogram revealed occlusion of hepatic artery, suggesting that the emergence of
      new lesion was attributed to unequal distribution of the drug. Six weeks after a
      cessation of HAI, a subsequent CT scan showed a rapidly enlarged new lesion in
      S3, so that a surgical resection for this tumor was performed. The patient is
      alive without recurrence more than 10 months after the diagnosis of multiple
      liver metastases (2 months after the last surgery).

PMID- 20037320
TI  - [A case of a 14-month survival patient on advanced esophageal cancer with
      uncontrolled brain metastasis completely responding to nedaplatin, adriamycin,
      plus 5-FU (NAF) therapy].
AB  - This case was a male patient, about 50 years old. He received a curative
      operation for advanced esophageal carcinoma [poorly differentiated squamous cell
      carcinoma type, Lt, pT3 (pAd) pN3, pstage III] in March 2005. He also received
      adjuvant chemotherapy of 5-FU plus cisplatin (CDDP). Fourteen months later (May
      2006) from surgery, metastases to the left lung and left subclavian lymph nodes
      were diagnosed, so he received first-line triplet combination chemotherapy (NAF
      regimen; nedaplatin 60 mg/m2: day 1, adriamycin 50 mg/m2: day 1, 5-FU 700 mg/m2:
      day 1-5). According to the 9 courses of treatment of this regimen, complete
      response for these metastases was observed and first-line chemotherapy was
      finished. However, a severe headache appeared 3 months later, and he had a
      diagnosis of solitary 5 cm brain metastasis by MRI. Excision of the metastasis
      was performed with sequential whole-brain radiation therapy (30 Gy). Five months
      later, diffuse and multiple brain metastases relapsed, and second-line
      chemotherapy did not respond well, and finally he was died 3 months after
      palliative care. But, completely controlled metastases (lung and lymph node) by
      first-line chemotherapy did not relapse again in all his clinical period. If an
      anticancer therapy goes in complete response in an advanced esophageal carcinoma
      patient, we should consider about a rare brain metastasis in order to find out as
      small and solitary state.

PMID- 20037321
TI  - [A case of effective photodynamic therapy for local recurrence after definitive
      chemoradiotherapy for esophageal cancer].
AB  - We performed a photodynamic therapy for local recurrence after chemoradiotherapy
      for esophageal cancer. The patient was a 60s man, who presented dysphasia.
      Esophagoscopy, CT and FDG-PET revealed an advanced esophageal cancer with
      mediastinal lymph node metastasis. He rejected a surgical treatment and underwent
      chemoradiotherapy, then achieved CR once. Subsequent FDG-PET, however, showed
      slightly FDG uptake at primary focus of the esophagus. Endoscopic biopsy specimen
      from Lugol's unstained lesion of the esophagus revealed squamous cell carcinoma,
      and he was diagnosed as a recurrence of the esophageal cancer. He underwent
      chemotherapy again, but the recurrent lesion enlarged. Because the control of the
      metastatic lesion was excellent and the recurrent lesion was considered as a
      superficial cancer, he was performed photodynamic therapy. Two months after
      photodynamic therapy, the esophagoscopy and FDG-PET showed no findings of the
      recurrence of the esophageal cancer. It was suggested that photodynamic therapy
      for local recurrence after definitive chemotherapy for esophageal cancer was
      effective and relatively safe.

PMID- 20037322
TI  - [Intra-peritoneal chemotherapy for scirrhous gastric cancer].
AB  - Preoperative intra-peritoneal chemotherapy (IPC) for scirrhous gastric cancer
      (SGC) has been performed and followed after laparoscopic diagnosis of peritoneal
      metastasis (P) or washing cytology (CY) in our hospital. Between 2002 and 2005,
      15 SGC patients were treated with 3 times of IPC using CDDP (50 mg/body) before
      operation (CDDP group). Between 2006 and 2008, 9 SGC patients were treated with
      IPC using docetaxel: DOC (40 mg/m2) and treated with systemic chemotherapy using
      S-1 (80 mg/m2) before operation (DOC group). Cases with P (+) or CY (+) were
      detected in 80% in CDDP group and in 89% in DOC group. Gastrectomy was performed
      in 67% of CDDP group and in 56% of DOC group. All of the 15 patients died in CDDP
      group but 4 of 9 were still alive in DOC group. The median survival time of DOC
      group (22 months) was longer than that of CDDP group (10 months, p=0.123). Thus,
      preoperative IPC using DOC combined with systemic chemotherapy using S-1 should
      be effective treatment for SGC.

PMID- 20037323
TI  - [A case of long-term survival in P1CY1 gastric cancer responding to combined
      chemotherapy with low-dose CDDP intraperitoneal administration].
AB  - We reported a case of P1CY1 gastric cancer with intraperitoneal chemotherapy
      after surgery for more than four years. The patient was a 69-year-old male who
      had suffered from Type I+Type 0 IIc, T3 gastric cancer. He underwent total
      gastrectomy with D2 dissection. Operative findings revealed P1CY1, and it
      resulted in non-curative resection. After surgery, combined chemotherapy with low
      dose CDDP intraperitoneal administration and UFT, and then combined chemotherapy
      with paclitaxel and 5-FU were performed. He also underwent palliative surgery for
      intestinal obstruction resulting from carcinomatous peritonitis. He achieved long
      term survival by multidisciplinary therapy of chemotherapy and surgery.

PMID- 20037324
TI  - [A case of long-term survival of recurrent gastric cancer successfully treated
      with multidisciplinary therapy].
AB  - A 73-year-old male patient underwent total gastrectomy for advanced gastric
      cancer in December 2000. The final diagnosis was 1 MU, ant, type 3, 67x47 mm, pT2
      (ss), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0, fStage II, tub 2, int, inf beta, ly3,
      v3, 2 L, post, type 2, 42x40 mm, pT2 (mp), pN1 (#1, 3, 4d), sP0, sH0, CY0, cM0,
      fStage II. Although we began adjuvant chemotherapy with UFT 300 mg/day, a
      solitary liver metastasis in the S6 sub-segment of the liver was diagnosed 15
      months after the first operation. He received RFA for liver metastasis, and the
      protocol was changed to S-1. Two-time recurrence of S6 was controlled by RFA but
      liver metastasis recurred again. So we performed posterior segmentectomy of the
      liver 30 months after the first operation. CT showed a solitary paraaortic lymph
      node metastasis 60 months after the first operation (24 months after
      hepatectomy). He showed a stable disease for 1 year, so he was given radiation of
      paraaortic lymph node metastasis at a total dose of 36 Gy (4.5 Gyx8 times) after
      72 months from the first operation. One hundred two months passed from first
      operation. The patient remains alive without any recurrence, and this
      multidisciplinary therapy proved to be effective.

PMID- 20037325
TI  - [A case of elder gastric cancer patient who relapsed at the local stomach wall
      and the regional lymph node at the time of six months after endoscopic submucosal
      dissection (ESD)].
AB  - A case is a woman of 81-year-old. She was admitted to our hospital for a close
      examination of anemia from her family doctor. Gastroscopy revealed a 15 mm
      diameter of the type 0-IIa+IIc lesion at the posterior wall to the lesser
      curvature of the gastric body. And the biopsy of the lesion revealed a moderately
      differentiated adenocarcinoma (tub2). In consideration of the gastrectomy at this
      point, but firstly, an endoscopic submucosal dissection (ESD) was planned to
      perform for gaining the total pathological diagnosis of the lesion. Pathological
      findings revealed that the cancer cell invaded massively to submucosa (sm2), and
      that lymphatic permeation and venous permeation were also presented (ly2, v2). We
      explained it to the patient about the necessity of additional gastric resection,
      but she rejected the operation. So we had no choice but to observe the patient
      closely. Two months after the ESD, gastroscopy revealed no recurrent signs. But
      six months after the ESD, the local area of the stomach was revealed type 2
      advanced gastric cancer, and computed tomography (CT) revealed a lymphoid
      swelling at the side of lesser curvature. We performed distal gastrectomy and D2
      lymphoid dissection at this point. The final pathological diagnosis was T2 (ss)
      N2H0P0M0, Stage IIIA, based on the Japanese classification of gastric cancer.
      Adjuvant chemotherapy (oral fluoropylimidine) was interrupted in short period
      because of the side effects such as nausea, appetite loss, and diarrhea. There
      has been no recurrence for 1 year and six months since the operation. ESD is a
      minimally invasive technique and it is safe, convenient, and efficacious from the
      gastric functional point of view. However, the therapeutic strategies of the
      early gastric cancer, especially submucosally invasive gastric cancer, must be
      decided carefully and individually, considering the risk factors and the
      postoperative quality of life (QOL).

PMID- 20037326
TI  - [The colon cancer patient with multiple hepatic metastases and peritoneal
      disseminations was treated by hepatic arterial infusion chemotherapy and
      resection of the metastatic peritoneal dissemination with successive systemic
      chemotherapy--a case report of the long term survivor].
AB  - A 33-year-old man, who underwent ileo-cecal resection and sigmoidectomy for
      concomitant cecal cancer and sigmoid colon cancer which was diagnosed during the
      emergent operation for the perforated acute appendicitis, suffered simultaneous
      multiple hepatic metastases. Postoperative hepatic aerial infusion chemotherapy
      with 5-FU was done (total dose 63 g), and the metastases were successfully
      disappeared (CR). Although 16-month passed from the operation, locoregional
      recurrence at the colorectal anastomosis and peritoneal dissemination were
      occurred. Aggressive resections of the recurrent sites (anterior resection of the
      rectum, ileum, ascending colon and other recurrent sites) and successive systemic
      administration of FOLFOX4(9-course), FOLFIRI (20-course) and capecitabine (15
      course) were achieved. The patient survived for 4.5 years after the initial
      treatment.

PMID- 20037327
TI  - [Two cases of advanced rectal cancer resected successfully after neoadjuvant
      chemotherapy with FOLFOX regimen].
AB  - We describe here two cases of locally advanced rectal cancer treated with
      neoadjuvant chemotherapy prior to surgery. The first patient was a 54-year-old
      man whose chief complaint was bloody stool. A detailed examination revealed a
      rectal cancer with direct invasion of the primary rectal carcinoma into the
      prostate. Four courses of FOLFOX4 were administered as neoadjuvant chemotherapy.
      Because the invasion to the prostate was difficult to determine by subsequent CT
      evaluation, we performed a radical resection. The pathological examination
      revealed that all surgical margins were negative for malignancy and no metastasis
      to lymph nodes was found, therefore a surgical evaluation of curability was
      classified as A. The second patient was a 49-year-old woman whose chief complaint
      was irregular menstruation. A detailed examination revealed a rectal cancer with
      metastasis to an ovary and paraaortic lymph node. One course of FOLFOX4 and six
      courses of mFOLFOX6 (combined with bevacizumab in the first five courses) were
      administered as neoadjuvant chemotherapy. Subsequent examinations revealed
      significantly reduced primary tumor and the size of metastatic lesion. Given that
      metastasis to the paraaortic lymph node was difficult to determine, we performed
      a radical resection. The pathological examination revealed that all surgical
      margins were negative for malignancy, and the postoperative FDG-PET evaluation
      did not find FDG accumulation to paraaortic lymph node. We determined that there
      was no residual cancer and evaluated the surgery as curability B. We conclude
      that neoadjuvant chemotherapy against locally advanced rectal cancer may improve
      the curability of the surgery and save the surrounding organs.

PMID- 20037328
TI  - [Successful chemoradiation therapy for local control of rectal cancer with
      multiple bone metastases--a case report].
AB  - A 78-year-old man was admitted to our institute with the symptom of melena. The
      patient was diagnosed as having advanced rectal cancer (T4N2M1) with multiple
      bone metastases. Chemoradiation therapy was chosen for the local control because
      our proposal of colostomy was rejected. Concurrent chemoradiation therapy [46
      Gy/23 Fr+tegafur/uraci (l UFT 400 mg/m2)/calcium folinate (Leucovorin: LV 75
      mg/body)] resulted in a good partial response and the patient became
      asymptomatic. UFT/LV were administrated and most of the bone metastases were
      diminished. After 3 years of disease remission with good quality of life, local
      tumor recurred with the symptoms of melena and bowel obstruction. Colostomy and
      additional radiotherapy were performed for the palliation. He died after 4 years
      from the initial treatment. In advanced rectal cancer with distant metastases,
      chemoradiation therapy for local control plus systemic chemotherapy could be an
      alternative to improve quality of life.

PMID- 20037329
TI  - [A resected case of bleeding rectal cancer for Jehovah's Witness enabled with
      preceding colostomy and chemoradiation].
AB  - A 66-year-old woman, complaining of anal bleeding with anemia, was examined and
      diagnosed as advanced rectal cancer. Hemoglobin level at admission was 8.8 g/dL.
      Abdominal CT and MRI revealed a solid tumor of 43x45 mm in diameter. Colostomy
      was preceded for the purpose of bleeding control under the blood-augmented
      treatment on the 7th day of hospitalization. Preoperative chemoradiation was
      performed (a total of 40 Gy radiation+FOLFOX4 for 1 cycle) and obtained a
      significant size reduction of the tumor (reduction rate 75%). Abdomino-perineal
      resection of rectum was performed with 550 mL of hemodilutional autotransfusion 3
      months after the initiation of treatment. Pathological findings showed moderately
      differentiated adenocarcinoma with Stage III a. Vaginal fistula as an irradiation
      associated with complication was healed by duly performed debridement. The
      patient has survived for 31 months with no recurrence, which indicates that
      preceded colostomy and preoperative chemoradiation enabled a curative resection
      safely for the Jehovah's Witness patient with bleeding advanced rectal cancer.

PMID- 20037330
TI  - [A case of duodenal penetration by indwelling catheter during hepatic arterial
      infusion chemotherapy].
AB  - We report a patient with hepatic metastasis of descending colon cancer who
      underwent hepatic arterial infusion chemotherapy using 5-fluorouracil (5-FU) and
      CDDP, with an indwelling catheter and port system by GDA coil method. Since the
      tumor became smaller after five months, we decided to follow her up as an
      outpatient. Considering the possibility of its recurrence, the catheter-port
      system remained in her. Two and half years later, the recurrent hepatic
      metastasis was recognised and the hepatic arterial infusion chemotherapy was
      fulfilled again. The tumor obviously reduced and the same treatment was
      continued. However, he was hospitalized with a complaint of hematemesis. Upper
      gastrointestinal endoscopy revealed a projection around the splitting catheter in
      the duodenal bulb. Therefore, we embolized with coil under angiographic guidance
      in order not to bleed from the artery and removed the port. With this experience,
      special attention for the catheter port system must be taken if one considers a
      long-term treatment. Thereby, we report on the complications of the catheter-port
      system.

PMID- 20037331
TI  - [Case report of infected pseudo-aneurysm after intra-arterial chemotherapy].
AB  - A 63-year-old man admitted to emergency center of our hospital with fever and
      obstructive jaundice. Computed tomography (CT) showed a mass in the head of the
      pancreas and a dilated bile duct. After performing preoperative biliary drainage,
      we conducted pancreatico-duodenectomy (PD-II: T3, N1, stage III). As adjuvant
      chemotherapy, the patient received a hepatic arterial infusion with 5-FU to
      prevent liver metastasis. A catheter was placed in the right femoral artery and
      intra-arterial chemotherapy was carried out for one week. After the completion of
      chemotherapy, swelling and redness of the right inguinal region was observed. CT
      revealed an infected pseudo-aneurysm of the femoral artery. Despite intravenous
      antibiotic therapy for 2 days, bleeding and pus discharge at the catheter root
      were observed. He immediately underwent drainage and primary suture to stop the
      bleeding. Two weeks after surgery for the infected pseudo-aneurysm, a right
      external iliac-femoral bypass operation was performed. Five weeks after surgery,
      he was discharged without further incident. In such cases, it is advisable to
      drain the infected pseudo-aneurysm following a prompt diagnosis, and perform a
      secondary bypass operation.

PMID- 20037332
TI  - [A case of postoperative multiple liver metastases of pancreatic cancer
      successfully treated by combination chemotherapy with weekly high-dose 5-FU
      hepatic arterial infusion plus systemic infusion of gemcitabine].
AB  - We report a case of a 65-year-old man with postoperative multiple liver
      metastases of pancreatic cancer successfully treated with weekly high-dose 5-FU
      hepatic arterial infusion chemotherapy plus systemic infusion of gemcitabine. The
      patient was admitted because of suffering from epigastralgia and jaundice. He
      underwent pancreaticoduodenectomy for pancreatic head cancer and received
      postoperative adjuvant chemotherapy of gemcitabine. Abdominal CT after 6 months
      showed multiple liver metastases. Then we started a systemic gemcitabine (1,000
      mg/body) infusion and weekly high- dose 5-FU (1,500 mg/body) hepatic arterial
      infusion chemotherapy. After 26 times of treatment, CT indicated that the tumors
      completely disappeared. He survived for 34 months after surgery. It has been
      suggested that this combined chemotherapy might be an effective treatment to
      control liver metastases of pancreatic cancer.

PMID- 20037333
TI  - [Three cases of biliary tract cancer with positive surgical margin obtained a
      long-term survival after multimodality therapy].
AB  - We report three cases of biliary tract cancer with positive surgical margin
      obtained a long-term survival after multimodality therapy. Case 1: A 58-year-old
      man had operated PPPD for middle part of biliary tract cancer. Final pathological
      findings revealed HM2. Hepatic metastasis and anastomotic recurrence were
      observed, postoperatively. RFA and chemoradiation therapy were performed against
      these lesions. Nevertheless, the patient died of sepsis associated with hepatic
      abscess caused by cholangitis 5 years and 10 months after surgery. Case 2: A 72
      year-old man had operated for upper part of biliary tract cancer. Intra-operative
      pathological findings revealed HM 2 and DM 2, extra-bile duct resection was
      performed for this lesion. After surgery, radiation therapy, systemic
      chemotherapy and hepatic arterial chemotherapy were performed, nevertheless the
      patient died of cancer 2 years and 6 months after surgery. Case 3: A 75-year-old
      man had operated for upper part of biliary tract cancer. Intra-operative
      pathological findings revealed HM 2 and DM 2, an extra-bile duct resection was
      performed for this lesion. After surgery, chemoradiation therapy, hepatic
      arterial chemotherapy and systemic chemotherapy were performed, nevertheless the
      patient died of cancer 3 years and 6 months after surgery.

PMID- 20037334
TI  - [A case of bile peritonitis caused by jejunal perforation after radiofrequency
      ablation for the multiple liver metastases from cholangiocarcinoma successfully
      treated with various interventional radiological procedures after
      pancreatoduodenectomy].
AB  - The case is a man in his 50s who had a curative surgical resection for
      cholangiocarcinoma in August 2006. The lesion was judged to be T3, N1, H0, P0, M0
      and Stage III, and then he received various treatments including thermotherapy,
      CD3-activated T lymphocyte therapy. Then from June 2007, he was treated for
      multiple liver metastases by GEM, radiofrequency ablation (RFA), stereotactic
      radiotherapy, S-1, dendritic cell therapy. But there were multiple liver
      metastases whose maximum size was 17 mm in diameter and he was introduced to our
      hospital. In September 2008, ultrasonography and CT fluoroscopy guided RFA was
      operated on him for the liver tumors with a safety margin. But 2 hours after the
      ablation, he complained of epigastralgia. CT examination revealed a bile
      peritonitis caused by perforation of the jejunum which has been anastomosed to
      the pancreas, and was adjacent to the avascular area caused by RFA in segment 4
      of the liver. We treated him by various interventional procedures including
      percutaneous drainage for bile leakage, pancreatic fistula, abscess in peritoneal
      cavity, and biloma in segment 3. Fifty days after the ablation, T-tube, with
      which pancreatic fluid and bile was induced from the cecal portion of the
      anastomosed jejunum to the anal side slipping through the perforated point, was
      successfully inserted through right flank, and resulted in complete recovery from
      a major technical complication of the bile peritonitis.

PMID- 20037335
TI  - [A case of hepatocellular carcinoma resolved by hepatic resection for local
      treatment].
AB  - A 76-year-old man with chronic hepatitis B was found to have a liver mass during
      a treatment of hypertension and atrial fibrillation at his local clinic, and was
      hospitalized to our hospital. Laboratory results on admission showed a mild
      hepatic impairment (grade B) and tumor markers AFP 12 ng/mL and PIVKA-II 10,169
      mAU/mL. Hepatic ultrasonography revealed a hypoechoic mass measuring 8-cm in
      diameter in the medial segment of the liver, and portography showed an extension
      of the right branch of the portal vein with no obvious tumor embolism. Hepatic
      arteriography disclosed an 8-cm hypervascular tumor fed by the right and left
      hepatic arteries. CTHA showed a high-density area between the medial and anterior
      segments, and the other high-density area measuring 2-cm in diameter in S5. The
      tumor site was observed as a portal perfusion defect area by CTAP. Hepatocellular
      carcinoma graded as cT3, cN0, cM0, and cStage III was diagnosed. Because the host
      liver function was good, hepatic resection was judged to be feasible, and the
      resection was performed. The postoperative course was favorable, and the patient
      was discharged from the hospital three weeks after surgery. It was considered
      that positive hepatic resection enabled radical treatment of hepatocellular
      carcinoma in patients with good liver function.

PMID- 20037336
TI  - [Successful surgical treatment for peritoneal dissemination of liver cancer after
      hepatectomy--a case report].
AB  - A 58-year-old female was admitted to Ogikubo Hospital for advanced hepatocellular
      carcinoma in April 2007. Pathological examination showed moderately
      differentiated hepatocellular carcinoma. Tumor marker increased the PIVKA-II
      level became 129 mAU/mL after the operation. FDG-PET was showed a solitary pelvic
      tumor sized about 2.5 cm in diameter. No other prominent metastatic lesions were
      demonstrated, so that a resection of intrapelvic tumor was performed in May 2008.
      The report which exhibited an asynchronism recurrence of peritoneal dissemination
      after hepatectomy is very rare. She has survived without a recurrence more than
      13 months after the resection.

PMID- 20037337
TI  - [A local control trial of skin malignant tumor].
AB  - Eighteen cases were diagnosed as skin malignant tumor in the past 4 years since
      2005. We performed a sentinel lymph node biopsy and backup evidement for the 18
      cases requiring a lymph node excision. Then, we reviewed its appropriateness. We
      also revealed interesting cases: Paget's out of breast 3, Merkel cell carcinoma
      2, and malignant melanoma 13. The range of age was 37-73 year-old, and the male
      and female ratio was 12:6. The primary sites were external genitalia 3, femoral
      region 1, brachium part 3, finger region 2, digit region 3, sole region 3 and
      back 3. A sentinel lymph node (SLN) identification rate was 13/18 (72.2%). For
      the inferior limb nuclear power generation skin malignant tumor, the
      identification rate of SLN was 100%. There was only one identified of SLN for
      superior limb/the soma nuclear power generation skin malignant tumor. We thought
      that a reexamination of the regional lymph node and the lymph flow was necessary.
      With regard to the inferior limb nuclear power generation malignancy skin tumor,
      it was considered that the appropriateness of the sentinel lymph node by the
      pigment method was useful.

PMID- 20037338
TI  - [Treatment strategy of breast carcinoma in the elderly patient-surgery, hormone
      therapy, and chemotherapy].
AB  - We report an elderly breast carcinoma patient with complication. The patient was
      a 91-year-old woman who had breast lump. The tumor was 3 cm in diameter. A core
      needle biopsy for breast tumor led to a diagnosis of an invasive ductal carcinoma
      positive for estrogen receptor and progesterone receptor, and positive for
      HER2/neu protein expression. She received tumorectomy. After operation, she was
      administered aromatase inhibitor. After six months from operation, metastases of
      lymph nodes and lung were observed. Although she had administered another
      aromatase inhibitor, the metastases were rapidly growing. Eight months after
      operation, she died from carcinomatous lymphangitis. Even the less invasive
      operation by local anesthesia can progress metastases rapidly in elderly breast
      cancer patients. This case suggested that a treatment strategy for elderly breast
      cancer patients should have been determined carefully.

PMID- 20037339
TI  - [Intra-arterial infusion chemotherapy for advanced breast cancer--5 cases of
      marked response].
AB  - In order to obtain less severe toxic reactions, while attaining maximal
      therapeutic effects, CPA, 5-FU and ADM or EPI have been administered through the
      catheter inserted into the internal thoracic artery with the IVR technique and
      the implantable infusion port system. Of the 181 patients with the unresectable
      or recurrent breast cancers attempted with intra- arterial infusion chemotherapy
      for the past 19 years, more than half of the patients showed a good response to
      this modality of the chemotherapy. In 4 out of the 5 patients with unresectable
      breast cancer, radical mastectomy became feasible following the marked response
      with the intra-arterial infusion chemotherapy. However, a distant metastasis
      proved to be a limiting factor for improvement of survival.

PMID- 20037340
TI  - [Advanced lung cancer with mediastinal lymph node metastasis and recurrence of
      brain metastasis completely responsive to combination chemotherapy and gamma
      knife radiosurgery--a case report].
AB  - We report a case in which advanced lung cancer with mediastinal lymph node
      metastasis and recurrence of brain metastasis was completely responsive to
      combination chemotherapy and gamma knife radiosurgery. The patient was a 61-year
      old woman, who suffered from advanced lung cancer (SCC) with bilateral
      mediastinal lymph node metastasis and contralateral lung nodule. She was treated
      with CBDCA combined with PTX. Bilateral lung nodules were surgically resected.
      Seven months after resection, solitary brain metastasis appeared, and gamma knife
      radiosurgery was performed. Histological efficacy of both primary lung tumor
      (SCC) and metastatic brain tumor was evaluated as Ef 3 (pCR). She has had no
      recurrence for 3 years after radiosurgery.

PMID- 20037341
TI  - [A case of retroperitoneal dedifferentiated liposarcoma successfully treated with
      IFM and CDDP].
AB  - A 53-year-old man was evaluated for a chief complaint of abdominal bloating.
      Physical examination revealed an abdominal distention and ascites, and CT showed
      multiple large retroperitoneal masses. The patient was diagnosed with
      retroperitoneal liposarcoma. Surgery was performed including the tumor, small
      bowel, and sigmoid resection, and an artificial anus was constructed. Multiple
      tumors in the peritoneum were noted. Large dark red tumors that were hemorrhagic
      were resected, but the yellowish tumors were unresectable. On histopathology, the
      dark red lesions showed dedifferentiated liposarcoma, and the yellowish lesions
      showed well-differentiated liposarcoma. One month postoperatively, peritoneal
      dissemination increased including nodular infiltration of the artificial anus and
      multiple hepatic metastases. Despite VAC chemotherapy (VCR 1.5 mg, ACD 0.5 mg,
      CPA 900 mg), progressive disease (PD) was noted. As second-line chemotherapy,
      weekly IFM (2 g)+CDDP (30 mg) was given. Shrinkage of the tumor infiltrates in
      the artificial anus, decreased abdominal bloating, and improved QOL were
      observed. A partial response (PR) against peritoneal dissemination was achieved.
      However, hepatic metastases increased, and the patient died 6 months after
      surgery. This case suggests that IFM+CDDP may be useful in dedifferentiated
      liposarcoma.

PMID- 20037342
TI  - [Radio-frequency ablation (RFA) for post-chemotherapeutic metastatic germ cell
      tumors as minimally invasive salvage therapy].
AB  - Radio-frequency ablation (RFA) has been successfully applied for local control of
      metastatic tumor. The aim of this study was to assess the effectiveness and
      safety of RFA to post-chemotherapeutic metastatic germ cell tumors (GCTs). As
      combined modality therapy, RFA was performed to 42 tumors in 19 patients of GCTs
      at our institution between November 2000 and December 2008. RFA was performed for
      10 liver metastatic tumors (in 6 cases), 32 lung metastatic tumors (in 13 cases),
      and median age was 36 years old (range 20-53) and the median tumor size was 12 mm
      (range 2-40). We used Cool-tip RF system (straight electrode needle of the
      internal cooling type, Radionics, Palm Coast, USA) for RFA with ultrasound or CT
      fluorosent guidance under intravenous or local anesthesia. The therapeutic effect
      was assessed by the contrast-enhanced CT or MRI. When contrast enhancement was
      remained in the tumor, the treatment was repeated. The 28 evaluable lesions
      followed were with median 25 months in the term of the surveillance, and 9 tumors
      were treated by an additional session of RFA repeatedly. complete response (CR)
      was achieved in 12 out of 12 tumors (100%) with tumor maker normalization. On the
      other hand, 12 out of 16 tumors (75%) without marker normalization showed CR. All
      of the 24 tumors with tumor diameter of 30 mm or less achieved CR, and the tumor
      greater than 30 mm achieved no CR. Major complications included pneumothorax
      (n=9) and hemato-thoraxes (n=2), but no complications in surrounding organs. The
      chest drainage tube was required in 4 cases (36%). RFA might be an alternative
      therapeutic option of combined modality therapy as salvage therapy for post
      chemotherapeutic metastatic germ cell tumors.

PMID- 20037343
TI  - [A case of superior sulcus tumor resected after chemoradiotherapy and resulted in
      complete response].
AB  - We report a case of superior sulcus tumor performed chemoradiation followed by
      operation obtaining a long-term survival without relapse. A case is a male of
      fifties, who visited our hospital with the complaint of numbness in the ulnar
      side of the left arm and scapular pain. Computed tomography revealed a mass, 4 cm
      in diameter in the apical portion of the left lung extending to superior sulcus
      and supraclavicular region. The tumor decreased in size by 2 cm after induction
      chemoradiotherapy under clinical diagnosis of T3N0M0 superior sulcus tumor and
      then the apex of the lung and the chest wall was resected with some superior
      mediastinal lymph nodes. No residual viable tumor cells were seen in the resected
      tissues. He was followed-up by CT without adjuvant therapy and is alive with no
      sign of relapse 6 years after the operation, so the effect of induction
      chemoradiotherapy is evaluated to be complete response. Multimodality therapy
      with induction chemoradiation and surgery for superior sulcus tumor without lymph
      node metastasis appears promising.

PMID- 20037344
TI  - [Intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis in cases
      of primary lung cancer].
AB  - Intrapleural hypotonic cisplatin treatment, which was introduced by Ichinose and
      colleagues, was performed for 5 cases of primary lung cancer with carcinomatous
      pleuritis: one case intraoperatively, one case postoperatively and 3 unresected
      cases. Fifty microg/mL of cisplatin distilled water solution was administered
      into pleural cavity and drained 10 minutes later in the intraoperative case or 30
      minutes later in the bedside cases. No adverse effect was observed. For 2
      dissemination- dominant cases, 2 regimens of single cytotoxic agent followed by
      gefitinib were administered, and the two patients died in 26 and 69 months,
      respectively. For one case with dissemination and effusion, 5 regimens including
      combination chemotherapy were administered, and the patient died in 41 months.
      For 2 effusion-dominant cases, gefitinib was administered and one case is still
      in PR status for 21 months, and the other was alive for 19 months. Ipsilateral
      pleural effusion was controlled in all 5 cases. This therapy is helpful for
      systemic chemotherapy as a main therapeutic means in cases of lung cancer with
      carcinomatous pleuritis by controlling malignant pleural effusion and relieving
      dyspnea.

PMID- 20037345
TI  - [A case of pyothorax-associated lymphoma treated by operation following radiation
      therapy].
AB  - A 70-year-old man was admitted to our hospital with complaints of right back to
      anterior chest pain and fever. He had a history of artificial pneumothorax for
      tuberculosis when he was 21 years old. The chest CT showed a partial thickness of
      right pleural cavity. The decortication and fenestration were performed for
      pyothorax, and a diagnosis of pyothorax-associated lymphoma (PAL) was obtained by
      pathological examination. After the surgery, chest CT revealed a rapid tumor
      growth in three months and suspicion of invasion to the ribs. After radiation
      therapy with a total dose of 40 Gy was performed, right pleuropneumonectomy was
      carried out. The tumor was not remained in the specimen. Postoperative
      chemotherapy was not performed. He lived for 5 years after the operation without
      recurrence. It is important to control local recurrence for PAL with the combined
      therapy of operation, chemotherapy and radiotherapy.

PMID- 20037346
TI  - [A case of left inguinal malignant lymphoma occurred after radical operation for
      gastric cancer and gastrointestinal stromal tumor].
AB  - In March 2005, a 70-year-old male patient underwent distal gastrectomy with D2
      lymph node dissection for type 3 gastric cancer located in the lower-third of the
      stomach, and partial gastrectomy for submucosal tumor located in the upper- third
      of the stomach. A post operative pathological finding of cancer was T2N0P0H0M0 (f
      Stage II) and that of submucosal tumor was gastrointestinal stromal tumor.
      Although the adjuvant chemotherapy of S-1 was administered, it was discontinued
      because of cerebral infarction. Forty months after the operation, CT scan
      revealed a left inguinal lymph node swelling and recurrence of gastric cancer was
      doubted. FDG-PET scan confirmed increased uptake only in one lymph node of left
      inguinal region. In September 2008, left inguinal lymph node dissection was
      performed and its pathological finding was follicular lymphoma (grade 1). At
      present, the patient was doing well and showed no signs of recurrence. However,
      it is important to follow-up the patient carefully because the relapse rate of
      follicular lymphoma is comparatively high.

PMID- 20037347
TI  - [Assessment of chemoradiation therapy for advanced rectal cancer invaded the
      pelvic organ].
AB  - We assess the effect of chemoradiation therapy for four cases of advanced rectal
      cancer. The radiation therapy consisted of 40-50 Gy delivered in fraction of 2
      Gy/day. A treatment of 5-fluorouracil (500 mg/body) with l-leucovorin (100
      mg/body) intravenously once a week, or oral S-1 (100 mg/day/body) for four weeks,
      was given during radiation therapy. Efficacy for primary carcinoma was evaluated
      as partial response in all four cases. We performed a curative operation in two
      cases. Histological efficacy for primary tumors was diagnosed as Grade 2 and
      Grade 3. Grade 3 adverse effect for neutropenia occurred in one patient, and
      Grade 3 adverse effect for appetite loss occurred in 2 patients. All cases
      survived without a recurrence for a period of 4 months-5 years and 3 months.
      Chemoradiation therapy was safe and an effective treatment prior to curative
      operation for advanced rectal cancer which invaded the pelvic organ.

PMID- 20037348
TI  - [A resected case of pathologically complete response of a pelvic recurrence from
      rectal cancer after chemoradiotherapy with S-1].
AB  - The patient was a 58-year-old man who had been performed a low anterior resection
      for an advanced upper rectal cancer (T3N0M0, Stage II). At fourteen months after
      primary operation, follow-up CT scan, MRI and FDG-PET showed a pelvic recurrence
      located at upper presacral region. Following radiotherapy combined with S-1, we
      performed a curative surgical resection. Pathologically, an extensive fibrosis
      was shown without a tumor cell. Complete surgical removal of the recurrent
      disease remains the best chance of cure after a local recurrence. But in the case
      of recurrent tumor located in upper presacral region and extended to the pelvic
      side-wall, it is very difficult to achieve negative resection margins. So
      selection of patients is very important to reduce the risk of positive surgical
      margins. We experienced a resected case of pathologically complete response of a
      pelvic recurrence from rectal cancer after chemoradiotherapy with S-1. This case
      suggests the neoadjuvant chemoradiotherapy has potential to improve management of
      locally recurrent rectal cancer.

PMID- 20037349
TI  - [A case of locally recurrent rectal cancer responding to radiation and
      chemotherapy with S-1].
AB  - We describe a case of locally recurrent rectal cancer that was successfully
      treated with radiation and chemotherapy with S-1; this treatment resulted in long
      term survival of the patient with a good performance status. A 51-year-old man
      underwent Hartmann's operation for advanced rectal cancer. At 6 months after the
      surgery, a pelvic computed tomography (CT) scan showed a local recurrence of the
      rectal cancer. The patient's serum CA19-9 level had increased to 3,200 U/mL. The
      tumor was unresectable, so that radiation therapy was administered to the pelvic
      region at a total dose of 56 Gy, followed by oral chemotherapy with S-1 for 2
      years. After these treatments, the serum CA19-9 level returned to normal. No
      signs of tumor recurrence were observed as of 3 years and 5 months after the
      confirmation of local recurrence. A combination of radiation therapy and oral
      administration of S-1 could be a useful treatment for unresectable locally
      recurrent rectal cancer.

PMID- 20037350
TI  - [Our experiences of preoperative chemoradiotherapy for rectal cancer with
      invasion to adjacent organs].
AB  - We reviewed clinical records of 10 cases with preoperative chemoradiotherapy to
      evaluate the clinical effectiveness of the chemoradiotherapy for T4 rectal
      cancer. The preoperative radiation therapy consisted of 40-50 Gy delivered in
      fractions of 1.8-2.0 Gy per day for five days per week. A treatment of 5
      fluorouracil (500 mg/body) per day intravenously, or oral UFT-E (300 mg/m2) with
      l-leucovorin (75 mg/body) per day, or oral S-1 (80 mg/m2) per day for five days
      per week, was given during radiotherapy. Grade 1 or 2 adverse effects occurred in
      3 patients during chemoradiotherapy, but a completion of chemoradiotherpy was
      achieved in all of the 10 patients. Invasive findings to the adjacent organs
      identified by CT and MRI disappeared in 6 cases with complete or partial response
      1 month after chemoradiotherapy. Although the adjacent organs were also removed
      during surgery in 7 patients, curative surgery was performed in 7 patients. There
      was no histological invasion to the adjacent organs in 4 patients, and one
      patient had a histological complete disappearance of tumor. Although
      complications after surgery were found in all of the patients, they were improved
      by conservative treatment. Two of 7 patients with curative surgery had
      recurrence, but the rest of them survived without recurrence. Preoperative
      chemoradiotherapy was expected to be a safe and effective treatment to improve
      the resection rate and prognosis for T4 rectal cancer.

PMID- 20037351
TI  - [Evaluation of preoperative chemoradiation therapy for lower rectal carcinoma
      using DWIBS].
AB  - We investigated the efficacy of diffusion-weighed whole body imaging with
      background body signal suppression (DWIBS) in assessing effects of chemoradiation
      therapy (CRT) on rectal carcinoma. DWIBS was performed in patients (n=12) with
      primary rectal carcinoma undergoing preoperative CRT before and 3 weeks after the
      treatment. Each patient received a total irradiation dose of 45 Gy at a single
      dose of 1.8 Gy administered once daily. Parallel to this, in the 1st, 3rd and 5th
      weeks 350 mg/m2 5-fluorouracil and 35 mg/m2 l-leucovorin were administered for 5
      days. The apparent diffusion coefficient (ADC) was measured by DWIBS and surgical
      resection of the tumors enabled a correlation of ADC values with the pathological
      findings. With respect to histopathological grading of regression, two, five and
      five cases exhibited Grade 3, Grade 2 and Grade 1, respectively. In all patients,
      ADC values were higher after completion of CRT compared to those before it(
      1.23+/-0.26x10(-3) mm2/s vs 0.75+/-0.13x10(-3) mm2/s, p<0.001). After completion
      of CRT, mean ADC values were 1.71+/-0.38x10(-3) mm2/s, 1.25+/-0.10x10(-3) mm2/s
      and 1.02+/-0.08x10(-3) mm2/s for Grade 3, Grade 2 and Grade 1, respectively.
      These preliminary results indicate that DWIBS may be a valuable tool to assess
      effects of CRT on rectal carcinoma by using appropriate cut-off values.

PMID- 20037352
TI  - [A case of radiation therapy successfully treated liver and lung tumors arising
      from postoperative cecum cancer].
AB  - The patient was an 85-year-old man who underwent a rt-hemicolectomy,
      cholecystectomy and choledocholithotomy for cecum cancer and bile duct stone. The
      tumor was a well differentiated adenocarcinoma, type 2 in the Japanese
      classification of colorectal carcinoma. The tumor was considered to be in stage
      II (ss, ly2, v0, n (-), P0, H0, M (-)). He did not receive any adjuvant
      chemotherapy. After 2 years and 3 months from the surgery, an abdominal MRI and
      an abdominal CT scan revealed a 30 mm hepatic nodule lesion. We diagnosed with
      liver metastasis of the cecum cancer. The patient refused both surgery and radio
      frequency ablation therapy. We chose radiotherapy for liver metastasis. He was
      given a total dose of 50 Gy/25 fractions. After 3 months from the radiotherapy,
      the tumor was reduced gradually and tumor marker (CEA) was normalized. The
      disease was diagnosed as CR because no tumors were detected. There has been no
      liver recurrence. But after 4 years and 6 months from the surgery, 20 mm lung
      nodules in rt-lower lung were revealed by chest X-ray. Once more, we chose
      radiotherapy for lung tumor. He was given a total dose of 66 Gy/33 fractions. At
      present, the tumor was reduced gradually. There has been no recurrence since his
      irradiation. If the case was made a good choice, radiation therapy appears to be
      effective for liver and lung tumors from the colorectal cancer.

PMID- 20037354
TI  - [A case of liver metastasis treated by cetuximab monotherapy with partial
      response].
AB  - BACKGROUND: Cetuximab in Japan is currently approved as a second or more line
      therapy for advanced metastatic colorectal cancer. CASE: We report a case of
      liver metastasis of colon cancer effectively treated by cetuximab after the
      progression and prolonged neural toxicity of the prior chemotherapy including
      oxaliplatin and irinotecan. A 61-year-old female suffered from unresectable
      multiple liver metastases of sigmoid colon cancer. She had already received
      irinotecan+S-1, mFOLFOX6+bevacizumab, FOLFIRI+bevacizumab, and hepatic arterial
      infusion of 5-FU+systemic infusion of irinotecan. Although liver metastases were
      stably controlled by those therapies, her peripheral neural symptom, initially
      caused by oxaliplatin, became worse after infusion of irinotecan. We decided to
      give her cetuximab monotherapy in the fifth-line setting. We investigated K-ras
      gene status on her colon cancer tissue previously resected, which showed a wild
      type. Her liver tumor showed a partial response evaluated with RECIST, and the
      status was maintained for more than four months. CONCLUSION: Cetuximab
      monotherapy can be used for those with prolonged neurotoxicity and might be
      effective for the patients with second or more line setting.

PMID- 20037353
TI  - [A case of rectal cancer with lung metastases responding to cetuximab].
AB  - We report a 73-year-old male patient who underwent low anterior resection for
      rectal cancer (Stage IIIb). Nine months after the surgery, multiple metastases of
      liver, lung, brain and lymph node were detected. He was treated with FOLFOX4 and
      FOLFIRI though lung metastases progressed and caused dyspnea. Cetuximab plus
      irinotecan therapy was dramatically effective, which improved his quality of life
      for over 10 months.

PMID- 20037355
TI  - [A case report of metastatic liver tumor from rectosigmoid colon cancer
      demonstrating a pathological complete response with FOLFOX and FOLFIRI
      treatment].
AB  - We report a case of multiple liver metastases of rectsigmoid colon cancer treated
      with systemic chemotherapy and hepatectomy. A 40s woman had undergone anterior
      resection of rectum for rectsigmoid colon cancer with multiple liver metastases.
      Then FOLFOX4 regimen was performed fifteen times, and FOLFIRI regimen was
      performed eleven times. After chemotherapy was enforced, an abdominal CT revealed
      that liver metastases were reduced in size (effect judgment of partial response).
      Hepatic resection of the right lobe and partial of S2 segment were performed.
      Pathological findings of the resected liver revealed no residual cancer cells,
      indicating that the histological effect of chemotherapy was complete response
      (CR).

PMID- 20037356
TI  - [A case of liver metastasis of rectal cancer demonstrating complete response for
      more than two years to mFOLFOX6].
AB  - A man in his fifties with rectal cancer underwent low anterior resection in
      another Hospital in January 2006. He was finally diagnosed with Stage III a (pA,
      pN1, H0, P0). The patient who had postoperative complication such as ruptured
      suture left the hospital in May 2006, when he was detected with multiple liver
      metastases and was referred to our hospital for systemic chemotherapy. Systemic
      chemotherapy with mFOLFOX6 was performed from May 2006. Grade 3 diarrhea and
      grade 2 peripheral neuropathy, nausea and vomiting were observed. After 6 courses
      of mFOLFOX6, MRI revealed metastasis had been disappeared and levels of CEA and
      CA19-9 were decreased below normal. The treatment has been discontinued.
      Recurrence was not observed for 30 months.

PMID- 20037357
TI  - [A case of rectal cancer successfully treated by multidisciplinary strategy for
      liver and pulmonary metastases].
AB  - We report a case of rectal cancer with distant metastases, which was successfully
      treated with multidisciplinary treatments. The 60s female underwent an abdomino
      perineal resection (APR) for low rectal cancer. One year after the APR, two
      hepatic metastases were found and initially treated by radiofrequency ablation
      and later by hepatectomy. One month after the hepatectomy, three pulmonary
      metastases of 10 mm in diameter were found in the right lung. Several regimens of
      chemotherapy (S-1, CPT-11 and FOLFOX6) were performed. After 3 years of
      chemotherapy, pulmonary metastases re- grew in size but no new lesion developed.
      Pneumonectomy was performed to remove all metastatic tumors. A half year after
      the initial pneumonectomy, a new metastasis was found in the left lung, which was
      again removed by surgery after 6 months of observation. Postoperative course was
      uneventful, and she is alive without recurrence for 7 years since the initial
      rectal surgery.

PMID- 20037358
TI  - [A case of pathological complete response of metachronous multiple liver
      metastases from colorectal cancer after mFOLFOX+bevacizumab chemotherapy].
AB  - A 25-year-old man with RS rectal cancer received a radical resection of the
      original tumor and lymph node dissection. Oral tegafur/uracil (UFT)/Leucovorin
      (LV) therapy has been used for adjuvant chemotherapy, as the pathological Stage
      was T3N1M0, Stage IIIa. After 10 months from operation, multiple liver metastases
      were recognized and not resectable. So a systemic chemotherapy by
      mFOLFOX6+bevacizumab was begun via CV port. After 5 courses of
      mFOLFOX6+bevacizumab, abdominal CT revealed liver metastases showed remarkable
      reduction in size. Hepatic resection of S6 segment was enforced, and the patient
      uneventfully discharged. Pathological findings of S6 segment revealed no residual
      cancer cells, indicating the histological effect of mFOLFOX6+bevacizumab was
      Grade 3. And no liver damage was recognized.

PMID- 20037359
TI  - [Two radically resected colorectal carcinoma cases with unresectable liver
      metastasis after adjuvant chemotherapy with bevacizumab].
AB  - Nowadays, the advancements of systemic chemotherapy for colorectal carcinoma
      improve a clinical response rate, and expand the possibility of resection which
      couldn't operable at the initial visit. In addition, the prognoses of the
      patients, who had a radical operation for metastasis, are clearly longer than the
      non-operable patients. Bevacizumab, anti-human VEGF monoclonal antibody, is
      significantly effective when used in combination with one of the systemic multi
      agent chemotherapy such as FOLFOX regimen or FOLFIRI regimen. We report here two
      cases with colon carcinoma, which had initially unresectable liver metastases,
      were respond to the treatment of systemic multi-agent chemotherapy with
      bevacizumab. Then, both cases were able to undergo radical resections of primary
      tumor and liver metastases safely.

PMID- 20037360
TI  - [Intermittent hepatic arterial infusion with systemic chemotherapy for metastatic
      colorectal cancer].
AB  - We report 5 cases of metastatic colorectal cancer with intermittent hepatic
      arterial infusion (HAI) and systemic chemotherapy (CPT-11, biweekly) in 2006
      2008. Two patients with poor performance status were for systemic chemotherapy,
      and 3 patients were initiated as third-line treatment or more. Among the 5
      patients, 2 patients were recorded as PR, 2 patients were as SD, and 1 patient
      was as NE. Three patients are alive with a mean follow-up of 19 months. HAI is
      intended to have few side effects compared with the systemic chemotherapy, and
      the treatment methods for these cases were not indicated for any of standard
      chemotherapies. But HAI alone is considered as insufficient treatment for
      unresectable liver metastasis, because HAI cannot be proved to have an apparent
      survival benefit. It is possible that a combination of regional and systemic drug
      treatments will be more effective than systemic treatment alone for unresectable
      colorectal cancer.

PMID- 20037361
TI  - [A new method of short-term high volume (6 g of 5-FU in a week) intermittent
      hepatic arterial infusion using repeated transient catheter insertion].
AB  - We report a case of liver metastases, which had hepatectomy twice and a partial
      lung resection after sigmoidectomy with partial bladder resection for advanced
      sigmoid colon cancer. The patient could not be tolerated the systemic
      chemotherapy, and percutaneous implantation of a catheter also could not have
      done with subcutaneous reservoir for hepatic arterial infusion because of an
      anomaly of hepatic artery branched-out from super mesenteric artery. Therefore,
      we tried an intermittent hepatic arterial infusion using a transient insertion of
      catheter to control the liver metastases' growth. A total amount of 6 g of 5-FU
      was continuously injected in a week by one insertion of catheter at the hepatic
      artery taking one day rest at day 4. During the next 21 months, a total of 11
      courses have been done. CEA and CA19-9 were changed from 15 ng/mL, 48 U/ mL to
      18, 30, respectively. The patient was able to keep working except for the
      duration of this treatment. This procedure could be one of the hepatic arterial
      infusion options.

PMID- 20037362
TI  - [A case report of multiple liver metastases from colorectal cancer effectively
      treated with systemic chemotherapy and hepatic arterial infusion].
AB  - A 61-year-old man admitted to our hospital for diarrhea and general fatigue was
      found in endoscopic and radiological examination to have sigmoid colon cancer
      with multiple liver metastases. The patient underwent sigmoidectomy (S, type 2,
      105x78 mm, sSI (urinary bladder), sN0 (0/22), sH3 (Grade C), sP0, sM0, sStage
      IV). Pathological report was following: tub2, pSI (urinary bladder), ly0, v1,
      pN0(0/22), PM0, DM0, RM0. After operation, the patient received systemic
      chemotherapy (CPT-11+UFT/LV) with hepatic arterial infusion therapy(HAI). We
      could not observe any severe adverse events. We conducted hepatectomy because of
      partial response by chemotherapy. As of this writing 41 months after surgery, the
      patient continues to do well with no signs of recurrence. The combination
      chemotherapy of CPT-11+UFT/LV with HAI was safe and effective treatment for the
      patients with unresectable liver metastases from colorectal cancer.

PMID- 20037363
TI  - [A case of advanced rectal cancer with severe liver dysfunction due to multiple
      liver metastases].
AB  - We report a case of rectal cancer with unresectable multiple liver metastases,
      which was worried about the transition from liver dysfunction to liver failure.
      The male patient in his 70s was diagnosed as advanced rectal cancer with severe
      liver dysfunction because of multiple liver metastases. Hepatic arterial infusion
      (HAI) chemotherapy, which was effective to reduce the size of metastatic liver
      tumors, was initially started. During HAI chemotherapy, sigmoid colostomy was
      performed. He recovered from liver dysfunction after he had been treated with
      13th cycle HAI chemotherapy. He was treated with the modified FOLFOX6 regimen
      following a resection of rectal cancer. Although the standard therapy for
      colorectal cancer with unresectable liver metastases is firstly systemic
      chemotherapy such as FOLFOX or FOLFIRI, it might be better to control the liver
      metastases by HAI chemotherapy when a liver function is severely damaged by
      extensive liver tumors.

PMID- 20037364
TI  - [A case of ascending colon cancer successfully treated for synchronous liver
      metastases with mFOLFOX6 after a resection of the primary tumor].
AB  - We report a case of ascending colon cancer successfully treated for synchronous
      liver metastases with mFOLFOX6 after a resection of the primary tumor. A 79-year
      old woman was diagnosed as having an ascending colon cancer with synchronous
      liver metastases. After right hemicolectomy, she was treated with mFOLFOX6. A
      partial response was observed after the fifth course and CEA decreased to a
      normal range (8 ng/mL). A complete response was observed after the ninth course
      and the treatment finished at the twelfth course. Sequentially, she was treated
      with UFT/LV/PSK after three courses of FOLFIRI regimen. The patient is alive
      without recurrence.

PMID- 20037365
TI  - [A case report of 4-year survival of the patient with transverse colon cancer
      with multiple liver and lymph node metastases--multidisciplinary approach].
AB  - A 47-year-old male presented to our Hospital in February 2005 with acute colonic
      obstruction due to transverse colon cancer. The patient had undergone emergency
      transverse colectomy with loop colostomy. After stabilization of patient's
      general condition, a further investigation revealed multiple liver metastases.
      The patient had a further multidisciplinary management with surgical lateral
      hepatectomy 10 weeks after the first presentation. Furthermore, radiofrequency
      ablation (RFA) used for other liver metastases, and likewise chemotherapy with S
      1. This patient also had 7 sessions of RFA within 3 years for different liver
      metastases. In May 2008, CT abdomen revealed metastases surrounding superior
      mesenteric artery lymph nodes and more of liver metastases. Chemotherapy started
      in May 2008 till February 2009 with mFOLFOX6+bevacizumab (a total of 16
      sessions). In November 2008, liver metastases vanished and lymph nodes had
      shrunken. In February 2009, we performed stereotactic radiotherapy on the lymph
      nodes metastases and one more session of mFOLFOX6, He showed no visible abdominal
      metastases on CT scan. The patient is currently in good health with no residual
      symptoms. The loco-regional cancer treatment with chemo, radiotherapy, RFA as
      well as surgery improved patient's survival with advanced colonic cancer and
      added to a quality of life.

PMID- 20037366
TI  - [A curative resection with the combination of portal vein branch embolization and
      systemic chemotherapy in a patient with synchronous multiple and bilobar
      colorectal liver metastases].
AB  - A 60-year-old man was admitted to our institution having a descending colon
      cancer with synchronous liver metastases. Tumor marker levels were remarkably
      elevated and the liver metastases were multiple and located at both right lobe
      and segment 4. Due to lack of the remnant liver volume, left hemicolectomy and
      intraoperative right portal vein branch embolization were performed as a primary
      operation. Three weeks after the operation, he started to undergo systemic
      chemotherapy by mFOLFOX6. After 8 courses of the treatment, grade 3 neurotoxicity
      appeared, and we changed the regimen to FOLFIRI. During a total of 18 courses of
      the chemotherapy, the periodic CT scans revealed the liver metastases to be PR or
      SD, and no other metastatic lesion was detected. After the rest of chemotherapy
      for 7 weeks, extended right hepatectomy was performed. He had an uneventful
      postoperative course and the tumor marker levels immediately returned to normal
      levels. He has been in good health without a recurrence for 10 months after
      hepatectomy. The combination of portal vein embolization and systemic
      chemotherapy may contribute to improve respectability of synchronous multiple and
      bilobar colorectal liver metastases.

PMID- 20037367
TI  - [A five-year survived case of more than 5 cm colorectal liver metastases treated
      with intraoperative microwave coagulation therapy].
AB  - A 54-year-old man underwent Hartmann's operation for rectal cancer in October
      2003. Diagnostic images showed a single liver tumor in segment 7 of the liver in
      March 2004. He had a non-B, non-C cirrhosis. Liver damage was defined as B and
      ICG retention rate after 15 minutes was 54%. Platelet count was 7x10(4)
      11x10(4)/mm3 and PT activity was 59%. The S7 tumor size was 6.5 cm in diameter,
      and we planned a partial resection of the liver. Intraoperative histological
      diagnosis of needle biopsy showed a metastatic adenocarcinoma from rectal cancer.
      Because of tuberculous peritonitis, it was difficult to control oozing from
      dissected plane. Therefore, we changed the method of operation from a partial
      resection to microwave coagulation therapy (MCT). To avoid a deteriorating liver
      function, we did not perform any adjuvant chemotherapy. He is alive without
      recurrence for five years after surgery. Nevertheless metastatic liver tumor is
      more than 5 cm and in cirrhotic liver, if the tumor located superficial
      parenchyma, MCT may have a possibility to be a curative treatment.

PMID- 20037368
TI  - [Two case reports of metastatic liver carcinoma with the effective treatment of
      radiofrequency ablation and intraarterial chemotherapy].
AB  - We report two cases of metastatic liver carcinoma with the treatment of
      radiofrequency ablation (RFA) and intraarterial chemotherapy. The 57-year-old man
      of Case 1 had resectable multiple liver metastases of rectal carcinoma in
      November 2007. He refused a liver resection, but accepted a low anterior
      resection of the rectum and RFA and intraarterial chemotherapy (5-FU 1,000 mg
      WHD). After this treatment, he had accepted systemic chemotherapy and found no
      liver recurrence within a year. The 66-year-old man of Case 2 had unresectable
      multiple liver metastases of locally-advanced esophageal carcinoma in July 2006.
      He had accepted radiochemotherapy (FP+65 Gy), and then RFA and intraarterial
      chemotherapy (5-FU 1,000 mg WHD). After this treatment, solitary brain metastasis
      and lymph node metastasis of mediastinum were found and treated, and now he has
      been alive with systemic chemotherapy.

PMID- 20037369
TI  - [Hepatectomy with microwave coagulation therapy for multiple liver metastases of
      rectal carcinoid--a case report].
AB  - A woman in her 50s was admitted to our hospital for the evaluation of liver
      masses. Low density areas at S5, S6 and S8 of the liver were revealed by enhanced
      abdominal CT scan. While exploring for the primary site, we observed a flat
      tumor, 10 mm in diameter, in the rectum at 10 cm from the anal ring, and local
      resection of the tumor was performed transanally. It was histologically diagnosed
      as a rectal carcinoid. During surgery, ultrasonography revealed eight hypoechoic
      masses at S4, S5, S6 and S8 of the liver. We conducted a partial hepatectomy (S8,
      S5/6) and microwave coagulation therapy. Histologically, the masses were
      diagnosed as liver metastases of rectal carcinoid. As of 27 months since surgery,
      liver metastases control is favorable, and no local recurrence has been observed.
      Hepatectomy with microwave coagulation therapy is believed to be locally
      effective in multiple liver metastases of rectal carcinoid tumor.

PMID- 20037370
TI  - [Two resected cases of pulmonary metastasis from post operative colorectal cancer
      after preoperative chemotherapy with FOLFOX].
AB  - We described two resected cases of pulmonary metastasis from postoperative
      colorectal cancer after preoperative FOLFOX chemotherapy. Pathologic histology
      inspection of the tumor was judged to be effective prior to resection. The first
      case is a 68-year-old male who underwent a sigmoidectomy as a stage III A sigmoid
      colon cancer in March 2003. Afterwards, distant metastases had occurred to the
      liver, the left lung and neck lymph nodes from 2003 to 2006. Three operations and
      systemic chemotherapy were performed. A new metastasis of the right lung occurred
      in November 2006. The FOLFOX chemotherapy was performed 7 times, the tumor was
      not changed in the image, and the effect judgment was SD. After the chemotherapy,
      a partial resection of the right lung was performed in November 2007. Half of the
      tumor resulted in necrosis on the specimen (Grade 1b). The second case is a 63
      year-old female who underwent an anterior resection of the rectum as a stage II
      rectal cancer in January 2000, a partial resection of the right lung as a
      metachronous right pulmonary metastasis in March 2003, and post operative
      chemotherapy (IFL) were performed. A new metastasis of the right lung occurred in
      September 2005. The FOLFOX chemotherapy was performed 4 times, the tumor was not
      changed in the image, and the effect judgment was SD. After the chemotherapy, a
      partial resection of the right lung was performed in April 2006. One third of the
      tumor resulted in necrosis on the specimen (Grade 1a). COMMENT: It was thought
      that FOLFOX chemotherapy can be a promising candidate for neoadjuvant treatment
      of pulmonary metastasis from postoperative colorectal cancer.

PMID- 20037371
TI  - [A case of surgical approach to the recurrence of the para-aortic lymph nodes
      after resection of rectal cancer].
AB  - A 63-year-old female diagnosed as rectal cancer underwent low anterior resection
      and received adjuvant chemotherapy (folinate/tegafur/uracil therapy). After 6
      months, lymph node metastasis was confirmed by an elevation of the tumor marker
      (CEA) and a FDG-PET image. After administration of 37 courses of mFOLFOX6
      therapy, surgical excision was performed to the lymph node recurrence, because it
      was difficult to continue mFOLFOX6 therapy with grade 3 neuropathy. After 8
      months from the last operation, no lymph node metastasis was appeared in the para
      aortic area.

PMID- 20037372
TI  - [Chemotherapy with bevacizumab (BV)+modified FOLFOX6 for unresectable colorectal
      cancer].
AB  - We examined efficacy and safety of bevacizumab (BV)+modified FOLFOX6 (mFOLFOX6)
      regimen for unresectable colorectal cancer. We had 16 patients: liver metastases
      8, lung metastases 4, local recurrences 2, and lymph node metastases 2, as for
      evaluable lesions. The response rate was 46.6%, and disease control rate was
      86.6%. Hepatic metastatectomy was done in two cases after PR response. There was
      1 infusion related reaction case, 1 tumor bleeding and 1 anal fistula as the
      adverse events. In conclusion, the BV+mFOLFOX6 is one of the effective and
      feasible regimens for unresectable colorectal cancer.

PMID- 20037373
TI  - [A case of advanced right colonic cancer successfully treated by surgery and post
      operative chemotherapy].
AB  - A 45-year-old male patient with right colonic cancer, of which clinical finding
      was SIM1 (No.216), Stage IV, underwent extended right hemicolectomy with
      paraaortic lymph node resection as surgical treatment. However, CY1 was detected
      and a final finding was SIM1 (No.216) H0CY1, Stage IV. After the operation, we
      administered 3-course of FOLFOX4 plus bevacizumab protocol, 3-course of FOLFOX4,
      6-course of FOLFIRI, and 6-course of IRIS for one year. The patient is presently
      alive with no sign of recurrence after 22 months.

PMID- 20037374
TI  - [A case of sigmoid colon carcinoma accompanied with hydronephrosis caused by
      peritoneal dissemination and para-aortic lymph node metastases markedly responded
      to chemotherapy].
AB  - The patient was a 64-year-old male diagnosed as advanced sigmoid colon cancer
      accompanied with hydronephrosis caused by peritoneal dissemination and para
      aortic lymph node metastases. We performed transverse colostomy in the end of
      June 2008. Though he got renal failure, he was recovered by dialysis and
      diuretic. He received chemotherapy with LV+5-FU in the middle of August,
      continuously with bevacizumab (BV)+mFOLFOX6 in the end of October. In December,
      an elevated CEA marker was decreased after these treatments. Sigmoidectomy was
      done in the beginning of February 2009, dissemination disappeared completely.
      Histologically, most mucinous carcinoma cells disappeared or denatured, with
      viable tumor cells slightly remained.

PMID- 20037375
TI  - [Extended lymphadenectomy for gastric regional lymph node metastasis from
      transverse colon cancer--a case report].
AB  - We report a case of transverse colon cancer with gastric regional lymph node
      metastasis. A 50-year-old man was admitted to our hospital for abdominal
      distension and abnormal evacuation. He was diagnosed with advanced transverse
      colon cancer with regional lymph node metastasis by a barium enema examination
      and computed tomography. In operative findings, the main tumor at splenic flexure
      had invaded greater omentum. Therefore, left hemicolectomy with D3 lymph node
      dissection including gastroepiploic lymph node (classified to No. 204) was
      performed. Histopathological examination revealed the metastasis to
      gastroepiploic lymph node. Six months after initial surgery, mediastinal and
      hilar lymph node swelling was detected by follow-up CT scan, although mFOLFOX6
      was administered as postoperative adjuvant chemotherapy. We therefore performed
      FOLFIRI as second-line chemotherapy. He had a stable disease during FOLFIRI.
      Extensive lymph node dissection of gastric region may be useful for advanced
      transverse cancer.

PMID- 20037376
TI  - [Neoadjuvant chemotherapy and pancreatoduodenectomy for locally advanced colon
      cancer].
AB  - A 62-year-old man was referred to our hospital with the chief complaint of a
      palpable abdominal mass. Type 1 tumor was found in the ascending colon on
      fiberscopic examination, and pathologic examination revealed moderate to highly
      differentiated adenocarcinoma. Computed tomography of the abdomen demonstrated a
      main tumor and an adjacent large mass which was suspected to be lymph node
      metastasis. The tumor invaded the superior mesenteric vein( SMV) and pancreas. On
      the first laparotomy, a curative resection was difficult, and chemotherapy was
      planned. The FOLFIRI regimen was effective, but adverse events such as fever and
      general fatigue gradually became pronounced. Even after the change to FOLFOX,
      these adverse events did not improve, and we therefore decided to perform a
      radical resection. The patient is still alive and disease-free 8 months after
      surgery.

PMID- 20037377
TI  - [Is it possible to predict lateral lymph node metastasis by their sizes in
      patients with lower rectal cancer?--analysis of paraffin-embedded sections].
AB  - Considering the advantages and disadvantages of lateral lymph node dissection in
      patients with lower rectal cancer, it would be ideal to select candidates for
      lateral lymph node dissection by preoperative imaging study. This preliminary
      study was performed to examine whether it would be possible to predict lateral
      lymph node metastasis by their sizes in patients with lower rectal cancer. In
      study-1, we measured the maximal and minimal diameter of 17 lateral lymph nodes
      from 2 patients on the paraffin-embedded slides and compared them to the
      diameters of the fresh specimen. In study-2, a relationship between the size of
      lateral lymph nodes and the presence of metastasis was examined in 259 lateral
      lymph nodes from 35 patients. The mean reduction rate after paraffin embedding
      was 56.8% (34.7-78.8) for the maximal diameter and 62.0% (36.7-80.5) for the
      minimal diameter. The maximal (p<0.01) and minimal diameters (p<0.01) were
      significantly greater in the nodes positive for metastasis than in the negative
      nodes. The area under the receiver operating curve was significantly greater for
      the minimal diameter than for the maximal diameter( p=0.07). The sensitivity,
      specificity, and accuracy for predicting metastasis was 78.6%, 83.7%, and 83.4%,
      respectively when the cut off of the minimal diameter was set at 3.41 mm, which
      corresponds to 5.50 mm in living bodies. In conclusion, determining the minimal
      diameter of the lateral lymph nodes by preoperative imaging studies may be useful
      for selecting candidates for lateral lymph nodes dissection.

PMID- 20037378
TI  - [Treatment for intrapelvic recurrence of rectal cancer--resection versus
      chemotherapy].
AB  - This retrospective study was performed to clarify problems associated with
      surgery for local recurrence of rectal cancer in recent years when new anticancer
      drugs have come out to be available. We compared the background characteristics
      and treatment outcomes of patients who underwent resective surgery (resection
      group, n=9) and those who received chemotherapy comprised of new aniticancer
      drugs (chemotherapy group, n=5) for intrapelvic recurrence of rectal cancer
      between 1997 and 2008. In the resection group, the types of surgery included were
      abdomino-perineal resection in 1, posterior exenteration in 4, total pelvic
      exenteration in 4 and 5 who underwent sacrectomy. In the chemotherapy group,
      chemotherapy was continued to second-line treatment in 4 patients and third-line
      in 1. Oxaliplatin was given to 3 patients, irinotecan to 3, and Leucovorin to 5.
      The two groups did not significantly differ regarding various background factors
      including age, sex, stage at resection of the primary lesion, and the interval
      between resection of the primary lesion and detection of recurrence. The overall
      survival period after the start of treatment for recurrence did not significantly
      differ between the two groups (p=0.73). Patient's selection seems to have become
      a more important factor for resective surgery for intrapelvic recurrence of
      rectal cancer in recent years when the efficacy of new anticancer drugs is
      expected.

PMID- 20037379
TI  - [A case of anal canal carcinoma with systemic lymph node metastases successfully
      treated by bevacizumab+mFOLFOX6 therapy].
AB  - We describe our experience with a patient who had unresectable anal signet-ring
      cell carcinoma with extensive metastases to the lymph nodes, lungs, and bones.
      The patient was treated with bevacizumab (Bev)+mFOLFOX6 and achieved complete
      response (CR). He was a man in his fifties, who visited a local doctor with the
      chief complaints of swelling in the axillary and inguinal regions. Signet-ring
      cell carcinoma was diagnosed by examination of a biopsy specimen from the
      inguinal lymph nodes. A search for the primary tumor was performed, and anal
      canal carcinoma with pagetoid spread was detected in the perianal region.
      Positron emission tomography-computed tomography (PET-CT) showed an accumulation
      in lymph nodes throughout the body, as well as in the lungs and the bones.
      Bev+mFOLFOX6 therapy was initiated. After completion of 4 courses, the lymph
      nodes were no longer palpable. PET-CT scanning showed no accumulation. During the
      8th course, tumor markers decreased to the normal range, and CR was diagnosed.
      When 13 courses had been completed, the patient experienced grade 3 numbness of
      the hands and feet, so his treatment was changed to Bev+FOLFIRI therapy. In
      conclusion, Bev+mFOLFOX6 therapy achieved 6 months of CR in our patient who had
      anal signet-ring cell carcinoma with systemic metastases, which seemed likely to
      have a very poor prognosis.

PMID- 20037380
TI  - [Expression of dihydropyrimidine dehydrogenase in primary colorectal cancer and
      liver metastasis--a relationship between mRNA levels in cancer cells and protein
      levels in cancerous tissue and effect of 5-fluorouracil].
AB  - PURPOSE: To compare mRNA levels in cancer cells and protein levels in cancerous
      tissue in order to evaluate the expression of dihydropyrimidine dehydrogenase
      (DPD). MATERIALS AND METHODS: The materials were resected specimens of primary
      colorectal cancer (n=88) and synchronous liver metastasis (n=15). The expression
      of DPD mRNA in cancer cells was quantified by reverse-transcriptase polymerase
      chain reaction (RT-PCR) using cancer cells obtained by micro-dissection of
      paraffin-embedded specimens (Danenberg tumor profiling method). The protein level
      of DPD was determined by enzyme -linked immunosorbent assay (ELISA). RESULTS:
      There was no relationship between the level of DPD mRNA and the level of DPD
      protein in primary colorectal cancers and liver metastases. The level of DPD
      protein tended to be higher in liver metastases than in primary lesions (p=0.08)
      without a significant relationship between the two values. There was no
      relationship between primary colorectal lesions and liver metastases in terms of
      the expression of DPD mRNA. The efficacy of 5-fluorouracil (5-FU or
      UFT)/Leucovorin did not correlate with the expression level of DPD mRNA or DPD
      protein of primary lesions (n=18). CONCLUSIONS: We should note the discrepancy of
      results between the two different methods and the lack of a relationship between
      the levels of DPD expression in primary lesions and liver metastases, when
      considering the efficacy of 5-FU-based regimens according to the DPD expression
      level in primary colorectal cancers.

PMID- 20037381
TI  - [Two cases of venous thrombosis occurred during systemic chemotherapy for
      colorectal cancer].
AB  - We reported two cases of venous thrombosis occurred during systemic chemotherapy
      for colorectal cancer. Case 1: A 68-year-old male, who had been operated for
      rectal cancer received systemic chemotherapy with liver and lung metastases.
      Three months after the chemotherapy, the chest CT showed venous thrombosis. Case
      2: A 53-year-old female, who had been operated for rectal cancer received
      systemic chemotherapy with lung metastases. Ten months after the chemotherapy,
      the contrastradiogram from catheter showed venous thrombosis. Venous thrombosis
      should be considered when CV ports were placed especially with systemic
      chemotherapy for colorectal cancer.

PMID- 20037382
TI  - [A case of regional advanced colon cancer accompanied with right femoral nerve
      paresis].
AB  - The patient is a man in his sixties. A hard tumor that fixed to right iliac bone
      as big as an adult fist could be palpated in the ileocecal region. He complained
      a cramp and pain in the right thigh. Computed tomography of the abdomen after the
      administration of contrast material showed an irregular shape tumor that highly
      invaded through right iliac muscle, and it widely attached to the right iliac
      bone. Any distant metastases were not detected. In the abdominal cavity, any
      peritoneal dissemination nodules were not detected. The tumor was completely
      removed by excising with periosteum of the iliac bone, iliac muscle, transversus
      abdominis muscle, and a part of psoas muscle and femoral nerve. The dead space
      after radical excision was filled with greater omental flap. In the microscopic
      examination, the tumor was diagnosed moderately differentiated adenocarcinoma
      with invasion to serosa, muscles, femoral nerve and periosteum and regional lymph
      nodes involvement. The carcinoma cell was not seen in the excised margin, thus it
      was judged that it was curative excision. If the colonic cancer obtains the
      curative excision even if the permeation of the limited part is advanced, an
      excellent prognosis can often be expected, and the role that the surgical
      operation plays as limited part treatment is large.

PMID- 20037383
TI  - [A case of cerebellum metastasis from colon cancer].
AB  - We report a case of cerebellum metastasis from transverse colon cancer, which had
      no evidence of recurrence in the thoracoabdominal region by chemotherapy and
      resection of liver and lung metastases after initial operation. The case is a 71
      year-old male. We performed a radical resection of transverse colon cancer (D2)
      in 2001. The finding was moderately-differentiated adenocarcinoma, se, n1, ly1,
      v2, H0, P0, M0, stage IIIa. Relapsing tumor, which metastasized to the liver in 3
      years, the right lung in 4 years and 8 months and the left lung in 5 years and 11
      months after initial operation, were totally resected. Following the partial
      resection of the left lung, he received a treatment with 12 times of mFOLFOX6 and
      S-1+PSK. There was a good control observed in the thoracoabdominal region with no
      metastases for 14 months. However, drift and dizziness developed in April 2008,
      and cerebellum metastasis was diagnosed by MRI. He underwent a partial resection
      of cerebellum tumor, radiation therapy and FOLFIRI. He has been alive for 1 year
      after the treatment of the cerebellum metastasis, and there has been no evidence
      of recurrence in the thoracoabdominal region in 8 years after initial operation.

PMID- 20037384
TI  - [Analysis of 12 cases of brain metastasis from colorectal cancer].
AB  - This retrospective study was performed to evaluate the outcomes of 12 patients
      with brain metastasis from colorectal cancer treated between 1999 and 2008. The
      range of patients was 33-72 years old (median: 64 years old). The male to female
      ratio was 2:1. The primary site was the colon in 4 patients and rectum in 8
      patients. The site of brain metastasis was the cerebrum in 8 and cerebellum in 4.
      All brain lesions were metachronously detected. Three patients had a single
      lesion each, while the remaining 9 had multiple lesions. The range of the period
      from the resection of the primary lesion to the detection of brain metastasis was
      144-2,062 days (median: 868 days). The types of treatment included whole brain
      radiotherapy after cerebral metastatectomy in three patients with a single
      lesion, whole brain radiotherapy only in 7 patients with multiple lesions, and
      modified FOLFOX6 (mFOLFOX6) regimen combined with whole brain radiation in
      recently treated two patients with multiple brain and lung metastases. The median
      overall survival period was 107 days. The longest survivor was a patient who
      survived for 505 days after the start of mFOLFOX6 plus radiation therapy. It
      appears that how we control metastases has become more important in recent years.
      For example, using new drugs, extracranial metastases of controllable cancer have
      become better controllable over longer periods.

PMID- 20037385
TI  - [Skeletal muscle metastasis of rectal carcinoma--a case report].
AB  - Skeletal muscle metastasis of carcinoma is comparatively rare. We report a case
      of metastasis to the quadriceps femoris muscle after the operation for rectal
      carcinoma. A 70-year-old man underwent rectal amputation in May 2007 due to
      rectal carcinoma. In May 2008, he noticed a painful tumor in the right femoral
      region. We obtained the diagnosis of recurrent rectal carcinoma by open biopsy.
      Simultaneously, lung metastasis was revealed by a close examination. Metastatic
      tumor resection was performed before chemotherapy, because it was important to
      preserve his performance status. From June 2008, chemotherapy was started. A year
      after the second operation, lung metastatic lesions were gradually progressed. At
      present, new skeletal muscle metastasis is not found. He is receiving
      chemotherapy in outpatient care. The resection of skeletal muscle metastasis made
      a contribution to his quality of life.

PMID- 20037386
TI  - [A case of 7 mm rectal carcinoid with lymph node metastasis].
AB  - A 67-year-old man was admitted to our hospital because of fecal occult blood.
      Colonoscopy revealed a 7 mm rectal submucosal tumor, which was diagnosed as
      rectal carcinoid on biopsy. No metastasis was found on abdominal CT scan. We
      performed an endoscopic mucosal resection (EMR), but the vertical margin of the
      specimen was positive. We therefore performed a laparoscopic low anterior
      resection. There was no residue of carcinoid tumor in the resected specimen, but
      metastasis to a pararectal lymph node was found. In general, endoscopic treatment
      is performed for SM invasive rectal carcinoid less than 10 mm in diameter.
      However, several cases of lymph node metastasis with small carcinoid tumor have
      been reported. Therefore, the possibility of lymph node metastasis must be
      considered in patients with rectal carcinoid.

PMID- 20037387
TI  - [Neoadjuvant chemotherapy with intraperitoneal paclitaxel for advanced
      gynecologic cancer].
AB  - OBJECTIVES: We evaluated safety and activity of intraperitoneal paclitaxel [=PTX
      (ip)] for neoadjuvant chemotherapy (NAC) of patients with advanced gynecologic
      cancer. METHODS: 13 patients with gynecologic cancer who had diffuse peritoneal
      dissemination received PTX (ip) with systemic chemotherapy (TC regimen) for NAC.
      After 3-6 courses of NAC, interval debulking surgery (IDS) was done. At IDS, we
      explored intraperitoneal cavity and debulked as much as possible, and examined
      pathological effects of NAC. RESULTS: PTX (ip) was well tolerated with apparent
      anti-cancer activity. Eleven patients were done with IDS after 3-6 NAC courses.
      Ten of 11 patients were completed an optimal surgery without extended resections.
      Eight of 11 patients with IDS had grade 2 (5 cases) or grade 3 (3 cases) effects
      of pathological examination. CONCLUSION: According to this exploratory research,
      we considered PTX (ip)=80 mg/m2 with PTX (iv)=115 mg/m2 and CBDCA (iv) AUC=4 as
      an optimum drug dose. Although evaluated in a small number of patients, PTX (ip)
      appeared to have safety and anti-cancer activity, and should be evaluated
      further.

PMID- 20037388
TI  - [Analysis of ovarian metastasis of colorectal cancer--a comparison between
      ovarian metastasis and peritoneal metastasis without involving ovaries].
AB  - This retrospective study was performed to clarify whether or not ovarian
      metastasis from colorectal cancer should be classified into peritoneal
      metastasis. We compared patient background data and prognosis between patients
      with ovarian metastasis (ovarian group, n=16) and female patients with peritoneal
      metastasis without involving ovaries (peritoneal group, n=22) treated between
      1998 and 2008. The two groups did not significantly differ in terms of other
      clinicopathological factors evaluated. The median overall survival period was
      13.8 months for the ovarian group and 16.7 months for the peritoneal group
      (p=0.96). The 3-year overall survival rate was 48.6%, 46.9%, and 11.5% for
      patients with ovarian metastasis only (P2), those with minute peritoneal
      metastasis without involving ovaries (P1), and those with multiple (numerous)
      peritoneal metastasis without involving ovaries (P3) (p=0.13), respectively.
      These results suggest that it is valid to classify ovarian metastasis as
      peritoneal metastasis. However, further collection of data may be needed to
      conclude that solitary ovarian lesion(s) would be classified into P2.

PMID- 20037389
TI  - [A patient with metachronous ovarian metastases of signet-ring cell carcinoma of
      the transverse colon showing long-term survival after surgery].
AB  - The patient was a 43-year-old female who consulted a local physician due
      primarily to lower abdominal pain. She was referred to our hospital for close
      evaluation and treatment. Since circumferential cancer was detected in the
      transverse colon by lower digestive tract endoscopy, the patient was hospitalized
      for surgical treatment. Transverse colectomy (Cur A) was performed,
      histopathological examination indicated signet-ring cell carcinoma of the
      transverse colon, and the lesion was diagnosed as type 4, SS, ly3, v0, n1 (+),
      Stage III a. Postoperative adjuvant chemotherapy was recommended, but the patient
      was psychologically unstable and strongly rejected chemotherapy. The patient was
      periodically followed-up after surgery, but a mass was detected in the left ovary
      by CT after 1 year and 6 months, and bilateral ovariectomy was performed with a
      diagnosis of ovarian metastasis. The histopathological diagnosis was signet-ring
      cell carcinoma, and the ovarian lesions were judged to be metastases of the
      transverse colon carcinoma. Since the patient did not consent to postoperative
      chemotherapy, as after the initial surgery, she was followed-up without
      treatment. She was admitted with ileus due to peritoneal metastasis 4 years and
      10 months after the initial surgery, and, despite of the surgery, she died due to
      carcinoma 5 years after the initial surgery.

PMID- 20037390
TI  - [Ovarian metastasis after complete response of colon cancer].
AB  - We report a case of ovarian metastasis after complete response of colon cancer. A
      55-year-old woman underwent a sigmoidectomy for sigmoid colon cancer with hepatic
      metastasis and para-aorta lymph node metastasis. After the operation, the patient
      was given chemotherapy with bevacizumab+mFOLFOX6. Nine months after the
      operation, the patient was judged to have achieved complete response. Thirteen
      months after the operation, right ovarian tumor was found and bilateral
      oophrectomy, hysterectomy and omentectomy were performed. Histopathologically the
      ovarian tumor was metastasized from colonic cancer. After the second operation,
      the patient was given chemotherapy with bevacizumab+FOLFIRI. At present, the
      patient remains disease-free for 6 months after the ovarian operation.

PMID- 20037391
TI  - [A case of successful treatment using octreotide acetate for occlusive ileus in
      terminal stage cancer].
AB  - We report a 35-year-old female bearing ovarian cancer who was suffering from
      intestinal obstruction due to multiple recurrences. The treatment of 300
      microg/day of octreotide acetate was started. The symptom of obstruction, such as
      vomiting and nausea, caused by intestinal obstruction was suddenly controlled and
      the quality of life was improved. Octreotide acetate can be applied for the
      management of intestinal obstruction caused by metastases at the terminal stage
      of cancer.

PMID- 20037392
TI  - [A case of urachal carcinoma with transverse colon fistula].
AB  - A 61-year-old woman was admitted to our hospital because of abdominal pain.
      Computed tomography showed an abscess in the anterior abdominal wall and an
      intraabdominal tumor. Biopsy from bladder dome presented adenocarcinoma. We
      diagnosed the tumor as urachal carcinoma and operation was performed. The
      resected specimen showed transverse fistula. In Japan, there is no report of
      urachal carcinoma with fistula to digestive duct. We think it is a cause of
      strong infiltration of the carcinoma. Curative resection for urachal carcinoma
      with fistula can lead to a better prognosis, in spite of its invasive character.

PMID- 20037393
TI  - [A case of super advanced gastric cancer responding to S-1+CDDP and S-1 single
      regimen which led to a clinical complete response].
AB  - A patient is a 62-year-old man who was presented by epigastralgia. He was pointed
      out super advanced gastric cancer with paraaortic lymph node metastasis and
      pancreatic invasion by gastrointestinal endoscopy (GIS) and computed tomography
      (CT). We diagnosed as cT4N3M0, and started with chemotherapy as follows. S-1 (120
      mg/day) was orally administered for 3 weeks followed by 2-week rest as one
      course, and CDDP (90 mg/body)was administered by intravenous drip on day 8.
      Partial response was indicated after 6 courses of this procedure. We changed the
      procedure to S-1 single treatment for 2 weeks followed by 2-week rest. After 12
      course of this procedure, he was attacked by brain infarction, the procedure was
      interrupted for about 8 months. After rehabilitation, an S-1 single treatment was
      restarted. The main tumor and metastatic lymph node appeared no change before the
      interruption of S-1 single treatment. So, we considered that complete response
      was continued. S-1+CDDP and S-1 single regimen appears to be effective for super
      advanced gastric cancer.

PMID- 20037394
TI  - [A case of unresectable type 4 gastric cancer which has kept a long-term partial
      response with adjuvant systemic chemotherapy].
AB  - A 69-year-old woman was admitted to our hospital with complaint of epigastric
      discomfort in February 2006. The detailed examination had revealed type 4
      advanced gastric cancer. An exploratory laparotomy was performed for the
      unresectable case due to peritonitis cartinomatoza. Postoperative S-1 monotherapy
      (100 mg/body, 4 weeks on, 2 weeks off) was started as an outpatient in April
      2006. After 3-course, partial response (PR) was observed for the primary lesion
      by gastrointestinal endoscopy. In April 2007, the regimen was changed to S-1 (100
      mg/body, 3 weeks on, 2 weeks off)+CDDP (60 mg/m2, days 8) combined chemotherapy,
      then the primary lesion showed a slight increase. Thereafter, the regimen was
      changed to S-1 monotherapy in March 2008, and S-1+CDDP combined therapy in July
      2008 again. PR was kept observed for three years successfully after the
      exploratory laparotomy. A case of type 4 unresectable gastric cancer was reported
      that the postoperative chemotherapy of S-1 was effective.

PMID- 20037395
TI  - [A long term survivor of advanced gastric cancer treated with multi-drug
      combination chemotherapy].
AB  - We report a case of 70-year-old man who was admitted to our hospital due to
      hematemesis in June 2004. He was diagnosed by gastroscopy as having a type III
      moderately-poorly differentiated adenocarcinoma. A computed tomography (CT) scan
      revealed multiple lymph nodes swelling (#13, #16), finally he was diagnosed with
      gastric cancer stage IV (cT3, cN3, cM1). He was treated with S-1, but lymph nodes
      swelling increased in size, and then in March 2005, the treatment was changed to
      a second-line chemotherapy consisting of CPT-11 and CDDP. Abdominal CT scan
      showed a remarkable reduction of #16b1 lymph node, and the second-line
      chemotherapy was continued until 23 courses. But in April 2007, gastroscopy
      revealed the enlargement of gastric lesion. He was treated by third-line
      chemotherapy consisting of paclitaxel and doxifluoridine. This therapy was
      effective and continued until 7 courses. However, the treatment gradually became
      resistant and he died in May 2008, which was 4 years since the initial diagnosis.

PMID- 20037396
TI  - [A case of long-term survival of unresectable-advanced gastric cancer due to
      chemotherapy].
AB  - The case was a 50s male with chief complaints of body weight loss and nausea. A
      clinical finding was Stage IV gastric cancer of poorly differentiated
      adenocarcinoma. We diagnosed it unresectable and started 5-FU+CDDP as the first
      line chemotherapy. Partial response (PR) was observed and progression free time
      was 7 months. After 9 courses of 5-FU+ CDDP, the tumor grew and an oral intake
      was getting impossible. Gastro-jejunostomy was performed and then started a
      weekly PTX as the second-line chemotherapy after operation. The response was
      progressive disease (PD) after 4 courses of weekly PTX. Then we started S-1+CPT
      11 as the third-line chemotherapy. We could continue S-1+CPT-11 for 9 courses
      without a severe adverse effect. Overall survival was 26.2 months.

PMID- 20037397
TI  - [A case of advanced gastric cancer with paraaortic lymph node recurrence reaching
      a long-term survival by S-1 chemotherapy].
AB  - A 55-year-old male patient with epigastralgia was diagnosed as type 3 gastric
      cancer at the lower gastric region. Total gastrectomy and D3 lymph node
      dissection were performed in our hospital. Pathological findings showed pT2N2M0,
      pStage IIIA. He was treated with 5'-DFUR and PSK therapy as adjuvant chemotherapy
      for 18 months after surgery. At 24 months after the operation, paraaortic lymph
      node recurrence was confirmed by computed tomography. He was treated with single
      agent S-1 in 10 courses on a 4-week dosing regimen with a 2-week interval. After
      4 courses, CT showed a disappearance of paraaortic lymph node. He was obtained a
      complete response. Now the patient is disease-free for 11 years after operation.

PMID- 20037398
TI  - [A case of gastric cancer with peritoneal dissemination which has been alive more
      than three years responding to intraperitoneal chemotherapy].
AB  - A 59-year-old man was admitted to our hospital for abdominal mass and found to
      have a gastric cancer with peritoneal dissemination. Three courses of neoadjuvant
      chemotherapy combined with S-1 and CDDP were performed. This chemotherapy showed
      a substantial reduction of the size of primary tumor and peritoneal dissemination
      by CT examination. Surgical resection consisted of distal gasterectomy and D2
      lymph node dissection was performed, and an ip catheter was placed through the
      douglas pouch, and the catheter was attached to the subcutaneous portal delivery
      system for ip chemotherapy. Operative cytology of ascites proved positive and
      remnant neoplasm cells were identified in the peritoneum. The pathological stage
      was determined as T3 N2 H0 P1 CY1 M0, pStage IV. Following surgery, we selected
      the ip administration of paclitaxel at a dose of 100 mg per body. Finally, the
      peritoneal dissemination was re-grown. However, we continued the ip chemotherapy
      for twenty-five times on ambulant basis. Most gastric cancer patients with
      peritoneal dissemination die within a few months, and there is no standard
      treatment for peritoneal dissemination from gastric cancer. In conclusion, a
      condition of no progression has been achieved and maintained for more than three
      years by intraperitoneal administration of paclitaxel for patient with peritoneal
      dissemination due to advanced gastric cancer.

PMID- 20037399
TI  - [A case of unresectable cardiac gastric cancer patient who maintained a long-term
      QOL with chemotherapy and detention of metallic stent].
AB  - A case was a 66-year-old man. He visited our hospital for dysphagia, abdominal
      distention and body weight loss. He was underwent gastro-endoscopy and made a
      diagnosis of the advanced cardiac gastric cancer. The early esophageal and
      gastric cancer also detected. Furthermore, computed tomography was performed and
      detected multiple liver and spleen, para-aortic lymph-node metastases and the
      ascites (suspected for dissemination). We decided that curative resection was
      impossible. Therefore, we performed an abdominal puncture to remove the ascites
      and combination chemotherapy with S-1 and docetaxel. The combination therapy was
      effective. The main tumor and multiple metastatic lesions were reduced. But after
      six months, a tumor marker was increased. The anticancer drug was changed to S-1
      and CDDP. After eight months from the first-line chemotherapy started, the
      stenosis was appeared at esophago-gastric junction. We performed balloon
      dilation, and a metallic stent was detention with gastroscopy and radiography at
      stenotic lesion. He improved swallowing and discharged from hospital. After
      eleven months from the first-line chemotherapy started, he was died of increased
      liver metastases and peritonitis carcinomatousa.

PMID- 20037400
TI  - [A novel formulation of cisplatin (CDDP)].
AB  - The study aimed to assess our newly devised CDDP delivery system designed to
      provide targeting potential and a sustained release of the anticancer agent.
      Seventy percent deacetylated chitin was applied as a drug carrier. We prepared
      two different types of systems with two different procedures: namely, system A
      with direct method and system B with indirect method. The targeting property of
      the system was evaluated ex vivo with measuring adhesive force between each
      system and human colonic mucosa. The release behavior of the CDDP from the system
      was examined in vitro. The anticancer activities of the released CDDP were also
      examined in vitro using human gastric cancer cell line, MKN-45. Each system was a
      viscose elastic solution. The adhesive forces of the novel systems were stronger
      at 37 degrees C than that of 25 degrees C. Each system provided a sustained
      release of CDDP. The released CDDP demonstrated effective growth suppression
      activity against the MKN-45 cancer cells. The novel systems basically showed a
      favorable targeting function and a sustained release of CDDP, which effectively
      provided a growth inhibition potential against human cancer cell line. Our newly
      devised CDDP delivery systems are promising as a novel approach to cancer
      chemotherapy.

PMID- 20037401
TI  - [A case of advanced gastric cancer treated with S-1 and S-1/paclitaxel showing
      complete response twice].
AB  - The patient was a 76-year-old man with advanced gastric cancer located in cardia,
      and was diagnosed to have an invasion to diaphragma and multiple lymph node
      metastases. We treated successfully with 12-course of S-1 chemotherapy. But
      second primary gastric cancer was detected in antrum 26 months after primary
      therapy. We treated with S-1/paclitaxel ( PTX) combined chemotherapy. S-1 (80
      mg/m2) was orally administered for 2 weeks followed by a week interval and PTX
      (50 mg/m2) was also administered days 1 and 8. One course of chemotherapy was 21
      days. GIF and abdominal CT revealed complete response (CR) after 3 courses of
      chemotherapy. We are now going on 6 courses of chemotherapy and the patient did
      not experience any grade 3 adverse effects.

PMID- 20037402
TI  - [A case of advanced gastric cancer with histological complete response after S-1
      chemotherapy].
AB  - A 58-year-old man of unresectable gastric cancer was treated with S-1 (120
      mg/body/day) after gastrojejunostomy. After 5 courses of orally administration of
      S-1 for 4 weeks and withdrawal for 2 weeks, partial response (PR) was obtained
      clinically and distal gastrectomy was performed. The histological diagnosis
      showed no residue of carcinoma with both HE and immunohistochemical staining. The
      patient has been in good health and no recurrence has occurred for about 4 years
      and 4 months after resection.

PMID- 20037403
TI  - [A case of advanced gastric cancer responding completely treated with S-1
      therapy].
AB  - A 61-year-old male complained of easy fatigue. Gastroscopy revealed a gastric
      carcinoma. CT showed No.3 and No.7 lymph nodes swelling. Distant metastasis was
      not found. S-1 (120 mg/day) was administered for 28 days followed by 14- day rest
      as one course. Total gastrectomy was performed for 2 weeks after the
      chemotherapy. Pathology revealed no cancer cells in the gastric wall and
      dissected lymph nodes. The pathological effect was judged as Grade 3. This case
      suggests that S-1 therapy may be useful for elderly patients and patients with
      poor renal function.

PMID- 20037404
TI  - [Three scirrhous gastric cancer cases with CY negativity in second-look staging
      laparoscopy after chemotherapy to whom curative surgery was carried out].
AB  - Case 1: A 77-year-old female with scirrhous gastric cancer was diagnosed as
      c4T3N1H0M0P0CY1/stage IV, and S-1/docetaxel combined therapy was carried out. The
      wall thickness of stomach improved after 11 courses. Case 2: A 48-year-old female
      with scirrhous gastric cancer was diagnosed as c4T3N1H0M0P0CY1/stage IV, and S
      1/CDDP/paclitaxel combined therapy was carried out. The wall thickness of stomach
      improved after 5 courses. Case 3: A 37-year-old man with scirrhous gastric cancer
      was diagnosed as c4T3N0H0M0P1CY1/stage IV, and S-1/CDDP/paclitaxel combined
      therapy was carried out. The wall thickness of stomach improved after 5 courses.
      In all cases, CY and P negativity was confirmed in second-look staging
      laparoscopy and curative surgery was carried out.

PMID- 20037405
TI  - [A case of the local advanced gastric cancer which became a resection possible in
      S-1/CDDP/lentinan neoadjuvant chemotherapy].
AB  - A 61-year-old man with esophagus invasive advanced gastric cancer and peritoneum
      dissemination underwent three courses of S-1/CDDP/Lentinan (LNT) combination
      neoadjuvant chemotherapies (T3N1P1H0, Stage IV) (It is S-1 80 mg/m2,CDDP 15 mg/m2
      and LNT 2 mg/body twice/week for two weeks) since down staging was obtained. We
      performed the surgery of total gastrectomy, splenectomy, D2 lymph node
      dissection, and Roux-en Y reconstruction in March 2008. With the surgical
      examination, there was no ascites and peritoneal dissemination. Although there
      was serious infiltration, we were able to remove it. In the histopathological
      effect judgment, it was Grade 1b. We changed the therapy to S-1 alone after the
      same chemotherapy for six months. One year after the operation, he is still alive
      one year after the surgery.

PMID- 20037406
TI  - [A case of bilateral pulmonary metastasis from gastric cancer performed radical
      thoracoscopic lobectomy after neoadjuvant chemotherapy].
AB  - A 40s male was performed proximal gastrectomy with D1+alpha dissection and
      interposition reconstruction for type 1 esophago-gastric junctional cancer in
      January 2002. Pathological findings were as follows: pap, se, ly0, v0, n1 (#3,
      1/9) stage IIIA, curability B. Adjuvant chemotherapy by 5'-DFUR (800 mg/day) was
      done for 1 year. Bilateral pulmonary metastasis was detected in left S6 (3.8 cm)
      and right S10 (3 cm) in February 2006. After S-1 (120 mg/day) was administered
      for 4 courses, right pulmonary metastasis had become scar, and the other was
      remained and growing. S-1 (100 mg/ day 1-21)+CPT-11 (120 mg div day 1, 15) was
      done for 6 courses. However, the tumor was growing. As no other lesions but left
      pulmonary metastasis in S10, radical thoracoscopic left lower lobectomy with ND1
      lymph node dissection was performed. Pathological finding was pulmonary
      metastasis from gastric cancer with no lymph node metastasis. There were no
      recurrences observed in May 2009 since gastrectomy was done 7 years ago, and 3
      years since pulmonary metastasis was detected.

PMID- 20037407
TI  - [A case of successful control of recurrent duodenal carcinoma receiving
      paclitaxel].
AB  - We have experienced a case of successful control of recurrent duodenal carcinoma
      receiving paclitaxel chemotherapy. A 61-year-old woman with epigastralgia was
      diagnosed with pyloric gastric carcinoma upon upper gastrointestinal endoscopy
      and biopsy. Distal gastrectomy with D2 dissection was performed. However, at the
      resected organ, the lesion was on the duodenum. So, we additionally resected the
      anal edge. And 13a, 13b, 12a, p lymph nodes were dissected for duodenal
      carcinoma. Later, the CEA level was increased, and abdominal CT scan showed
      swelling of paraaortic lymph nodes. Recurrence of the duodenal carcinoma was
      diagnosed in February 2007, and S-1 administration was begun. But, we dosed down
      with S-1 due to severe diarrhea. In spite of combined S-1 and CPT-11
      chemotherapy, the CEA level increased, and lymph nodes were getting larger. She
      then underwent the paclitaxel chemotherapy during the 5 months without severe
      side effects. The CEA level decreased significantly and metastatic lymph nodes
      were reduced observed by CT scan. Paclitaxel chemotherapy is effective for
      duodenal cancer.

PMID- 20037408
TI  - [A long-term survival case of liver metastasis of gastric cancer under
      interdisciplinary therapy].
AB  - We report herein a long-term survival case of liver metastasis after distal
      gastrectomy for gastric cancer. A 72-year-old woman, whom we performed distal
      gastrectomy with D2 lymph node dissection for type 2 gastric cancer at age 66,
      was diagnosed as pT2N1M0, stage II. No adjuvant therapy was performed. Liver
      metastasis was found 1 year and 7 months after surgery. PTX plus CPT-11 was
      performed. Six courses of therapy were done, and found cCR in the liver
      metastasis. A total of 23 courses of therapy were done. A recurrence of liver
      metastasis was found, transcatheter arterial chemoembolization (TACE),
      radiofrequency ablation( RFA)and operation were performed. She received S-1 plus
      CDDP, and cCR has been maintained for 6 years and 11 months after gastrectomy (5
      years and 4 months after liver metastasis) suggesting that the interdisciplinary
      therapy was effective.

PMID- 20037409
TI  - [A long-term survival case of hepatic metastases after curative gastrectomy by
      combined therapies].
AB  - A 74-year-old female was performed distal gastrectomy (f-T3N0H0P0CY0M0, Stage II)
      for gastric cancer in 2003. After 14 months, CT scan showed a metastasis in S7
      segment of the liver. We performed chemotherapies until seventh-line and radio
      frequency ablation (RFA). It finally got a long-term survival of 36 months
      postoperatively. RFA may be one of the useful therapies of liver metastasis from
      gastric cancer.

PMID- 20037410
TI  - [A case of metachronous liver metastasis from gastric cancer treated with
      multidisciplinary therapy including hepatectomy].
AB  - A 73-year-old man underwent a distal gastrectomy with dissection of D2 lymph
      nodes for type 2 gastric cancer at the front wall of pyloric antrum in June 2006
      (Pathological finding was moderately differentiated adenocarcinoma, T2, N0, H0,
      P0, M0, fStage IB). Although he was given UFT and PSK for postoperative adjuvant
      therapy, MRI showed a liver metastasis at segment 6 of the liver in June 2007.
      After 2 courses of S-1, posterior segmentectomy of the liver was performed. After
      hepatectomy, 5 courses of S-1 as adjuvant therapy were administered. However,
      another metachronous liver metastasis appeared at segment 8 in August 2008. After
      3 courses of S-1 and CDDP, we performed radiofrequency ablation (RFA) therapy and
      a good cauterization effect was obtained. There has been no recurrence for 3
      years since gastrectomy, or 2 years since the first liver metastasis. We
      experienced a case of metachronous liver metastasis from gastric cancer treated
      with multidisciplinary therapy that was beneficial for a long term survival.

PMID- 20037411
TI  - [A case in which intra-arterial chemotherapy for simultaneous hepatic metastases
      markedly improved AFP-producing gastric cancer].
AB  - The prognosis of most hepatic and lymph node metastases in AFP-producing gastric
      cancer is poor, and despite the use of multimodal therapy, the average survival
      period is reported to be approximately one year. Described here is one example in
      which intra-arterial chemotherapy for simultaneous hepatic metastases in AFP
      producing gastric cancer achieved a marked improvement. The patient is a 65-year
      old female. Distal gastrectomy was performed for Type II gastric cancer. L, type
      2, 5.5x2.4 cm, tub 2>por 1, pT2 (MP), int, INF b, ly2, v1, pN1, pPM (-), pDM (-),
      pH1: stage IV. The AFP level before surgery was 801.4 ng/mL and lowered to 65.8
      ng/mL after surgery, AFP-producing gastric cancer and simultaneous hepatic
      metastases (S4, single lesion) was diagnosed based upon imaging examinations. 5
      FU+epirubicin+MMC (FEM)intra-arterial chemotherapy was started one month
      following surgery, but because CT showed multiple new hepatic lesions(S4, S5)four
      months following surgery, DSM therapy was performed with hepatic arterial
      injections of MMC 10 mg, DSM 300 mg. Dynamic CT showed a reduction in size of the
      tumors in both S4 and S5, and at five months following surgery, hepatic arterial
      infusion chemotherapy FP (CDDP 5 mg+5-FU 250 mg weekly) was started and performed
      45 times in a 14-month period. During therapy, CR was achieved for the hepatic
      metastases and tumor marker levels were also normal. Because an introduction of
      contrast medium into the hepatic reservoir showed a narrowing of the hepatic
      artery and inflow of contrast medium into the splenic artery, arterial infusion
      was terminated. Following this, from the 20th month following surgery, S-1 (100
      mg/day: 4 weeks administration, 2 weeks rest) was started and from the third
      course (50 mg/ day: 4 weeks administration, 2 weeks rest), and the patient is
      currently undergoing a sixth course. Currently, 2 years and 4 months after
      surgery, there have been no recurrences. This suggests the possibility that intra
      arterial chemotherapy is an effective treatment method for hepatic metastases in
      AFP-producing gastric cancer.

PMID- 20037412
TI  - [A case of advanced gastric cancer with liver metastases resected successfully
      after S-1 monotherapy and S-1/CDDP combination chemotherapy].
AB  - The patient was a 75-year-old man, who was diagnosed with type 3 gastric cancer
      with solitary liver metastasis whose diameter was 12 mm. Distal gastrectomy with
      D2 lymph node dissection was performed in June 2008. S-1 monotherapy (120 mg/day,
      day 1-28/42 days) for liver metastasis started as the first-line chemotherapy.
      After 3 courses, the diameter of liver metastasis enlarged to 22 mm. Moreover, S
      1 and CDDP combined chemotherapy (S-1: 120 mg/day, day 1-21/ 35 days, CDDP: 60
      mg/m2, day 8/35 days) was performed as the second-line chemotherapy, nevertheless
      the diameter of liver metastasis enlarged to 26 mm. No distant metastasis without
      solitary liver tumor was observed for 6 months after gastric resection, so a
      partial hepatic resection was performed in February 2009. Five months after the
      operation, the patient is doing well and shows no signs of recurrence of the
      cancer. A combination gastrectomy with D2 lymphadenectomy and postoperative
      chemotherapy was considered to be a radical treatment for H1, Stage IV gastric
      cancer.

PMID- 20037413
TI  - [A case of the gastric squamous cell carcinoma recurred in the kidney 5 years and
      4 months after curative resection].
AB  - We experienced a case of gastric squamous cell carcinoma, which recurred in the
      left kidney 5 years and 4 months after curative resection. A 64-year-old man
      underwent total gastrectomy with D2 lymph node dissection and splenectomy for
      Type 2 advanced gastric cancer. The histological examination showed the squamous
      cell carcinoma of stomach. The final stage was T3N0P0H0M0, fStage II. After 5
      years and 4 months, the left renal tumor appeared and laparoscopic nephrectomy
      was performed. The histological findings showed the metastatic renal cancer from
      stomach squamous cell carcinoma. The gastric squamous cell carcinoma is very rare
      and the frequency in all gastric cancer has been reported 0.09%. Furthermore,
      this is the first report of the metastasis to the kidney of the gastric squamous
      cell carcinoma.

PMID- 20037414
TI  - [A case of recurrence gastric cancer patient who was post operated and multi drug
      chemotherapy was effective for administration of S-1 and docetaxel combination
      therapy].
AB  - Recently, chemotherapy against gastric cancer has been diversified with an
      appearance of new agents such as S-1, capecitabine, CPT-11, oxaliplatin,
      paclitaxel and docetaxel. But a prognosis of advanced or recurrent gastric cancer
      patient, who was failure of first- and second-line chemotherapy, was poor. We
      reported that a case of recurrence gastric cancer patient who was post operated
      and multi drug chemotherapy was effective for administration of S-1 and docetaxel
      combination therapy. A case was a 50-year-old man. He underwent distal
      gastrectomy and administered of multi anticancer drugs until about eight years
      after operation. But multi lung and liver and lymph-node metastases were
      appeared. We administered S-1 and docetaxel combination chemotherapy. After two
      courses, multi metastatic lesions were reduced in size, and tumor markers were
      decreased. The same combination therapy was administered for six courses, but
      metastatic lesions were increased again. At one hundred four months after the
      operation, he died in the palliative care unit.

PMID- 20037415
TI  - [A case of far-advanced gastric cancer with peritoneal dissemination and
      obstructive jaundice effectively treated with combination chemotherapy and
      interventional radiology].
AB  - A 70-year-old man was hospitalized for obstructive jaundice. Endoscopic
      examination disclosed Borrmann type 3 advanced gastric cancer from ECJ to the
      middle corpus. Laparoscopic examination demonstrated the disseminated nodules at
      hepatic hilum. After percutaneous biliay drainage, we implanted an expandable
      metallic stent utilizing this fistula and started combination chemotherapy with S
      1 and CDDP. Although a partial response was achieved at endoscopic examination
      after 4 cycles, gastric and biliary legions gradually showed tolerance to S-1 and
      CDDP. We attempted 3 cycles of weekly paclitaxel as second-line. However,
      paclitaxel was not effective, the patient died of cancer growth 12 months after
      the first admission. According to combination with IVR and chemotherapy, we
      treated effectively the patient suffering from far-advanced gastric cancer with
      peritoneal dissemination and obstructive jaundice.

PMID- 20037416
TI  - [Three patients successfully treated with orthopedic surgery for spinal paralysis
      due to spine metastasis of gastric cancer].
AB  - We report three patients who were successfully treated with orthopedic surgery
      for spinal paralysis due to spine metastasis of gastric cancer. Case 1: A 75-year
      old female had lower limb paralysis due to metastasis of Th1-Th3 one year and
      four months after total gastrectomy for gastric cancer. Although radiotherapy was
      carried out from the day following a paralysis appearance, the paralysis
      deteriorated from D to C. Then, when direct decompressive surgical resection had
      been performed eight days after the paralysis appearance, the paralysis improved
      from C to D. Case 2: A 50-year-old male had lower limb paralysis due to
      metastasis of Th2 three years and eight months after distal gastrectomy for
      gastric cancer. Paralysis had improved from C to D with direct decompressive
      surgical resection three days after the paralysis appearance and radiotherapy
      after surgery. Case 3: An 80-year-old male had lower limb paralysis due to
      metastasis of Th3 five years and eight months after total gastrectomy for gastric
      cancer. Paralysis had improved from B of a Frankel classification to C with
      direct decompressive surgical resection seven hours after the paralysis
      appearance and radiotherapy after surgery. When the spinal paralysis due to spine
      metastasis of gastric cancer appeared, the orthopedic surgery for QOL maintenance
      was considered to be one of the useful medical treatment options.

PMID- 20037417
TI  - [A case of primary gastric choriocarcinoma].
AB  - Primary gastric choriocarcinoma is an extremely rare and poor prognosis. A 73
      year-old man who had appetite loss was admitted to our hospital in May 2006.
      Abdominal CT showed tumor measured 9x7 cm in size between residual stomach and
      pancreas. Gastrointestinal endoscopy revealed that gastric posterior wall was
      compressed and soft necrotic elevated tissue with coagulation. Endoscopic biopsy
      specimens showed poorly differentiated adenocarcinoma. Total gastrectomy with D2
      lymphadenectomy, distal pancreatectomy, splenectomy, and partial resection of
      transverse colon were performed. Histological findings of resected specimens
      showed choriocarcinoma which demonstrated reactivity against anti-hCG antibody by
      immunohistochemical staining. Forty five days after the operation, skin
      metastasis appeared, and he died of this disease 60 days after the operation.

PMID- 20037418
TI  - [Local resection and jejunal patch duodeno-plasty for the duodenal
      gastrointestinal stromal tumor--a case report].
AB  - Many gastrointestinal stromal tumors( GISTs) were treated according to the
      guidelines in Japan. In this paper, our procedure of the local resection, minimal
      invasive surgery, the jejunal graft patching and an attractive new method of
      treating duodenal GISTs was reported. A 50-year-old woman with duodenal
      submucosal tumor was referred to our hospital. The gastrointestinal endoscopic
      examination, the computed-tomographic images, and the magnetic resonance images
      showed a 3.5 cm hyper vascular tumor at the posterior superior aspect of the
      pancreatic head. PET-CT images revealed accumulations only in the duodenal tumor.
      The endoscopic ultra-sonographic images and biopsy revealed that the tumor was
      positive for c-kit, as a periampullary GIST of the duodenum presumed pancreatic
      invasion. The authors showed a" conventional and safe" local resection and
      duodenoplastic surgical technique for duodenal GISTs, although some reports
      declared the efficacy of the Roux-en Y duodeno-jejunostomy in Japan.

PMID- 20037419
TI  - [Long-term survival after surgery and adjuvant imatinib in a patient with rectal
      GIST, local recurrence, liver metastases and mediastinal pleural metastasis].
AB  - Imatinib is a standard treatment for metastatic GIST. Surgery is an optional
      treatment for local recurrence and resectable liver metastasis. We report a case
      of high risk group rectal GIST with local recurrence, liver metastases and
      mediastinal pleural metastasis. Long-term survival (7 years and 10 months) was
      achieved with imatinib after resection. A 63-year-old man underwent a surgery for
      undifferentiated esophageal cancer and simultaneously was diagnosed a rectal
      submucosal tumor of 3 cm by digital examination in 2001. After 2 years, he
      underwent Miles' operation because of an increase of the rectal submucosal tumor.
      The histological examination revealed a high risk group GIST. PET-CT and CT
      pointed out a local recurrence and liver metastases that were resected in 2004.
      Adjuvant imatinib at a dose of 300 mg/day was started but the dose was reduced to
      300 mg/2 days due to a side effect. Resumption and discontinuation of imatinib
      had been repeated. In 2008, he received a resection of mediastinal pleural
      metastasis. Imatinib started again at a dose of 200 mg/2 days and no recurrence
      has been pointed out. Combined modality therapy with surgery and chemotherapy for
      the metastatic GIST may contribute to a long-term survival.

PMID- 20037420
TI  - [A case of rapid growth GIST successfully treated with resection after long-term
      use of imatinib].
AB  - We report a case of rapid growth GIST successfully treated with resection, which
      imatinib controlled it as a stable disease for three years. A 68-year-old woman
      underwent simple hysterectomy and bilateral oophorectomy for the pelvic tumor. In
      the operation, there were multiple disseminations in the greater omentum and
      peritoneum. After diagnosed as high risk GIST, the patient was treated with
      imatinib at a dose of 400 mg/day, and the tumor was controlled as a stable
      disease for 3 years. At the end of 2008, lower abdominal tumor grew rapidly and
      intra-abdominal hemorrhage appeared. Although sunitinib was administered at a
      dose of 37.5 mg/day, the tumor was enlarged, and sunitinib was stopped because
      the patient developed grade 3 diarrhea. IVR was tried to control abdominal
      hemorrhage, but it was unsuccessful. The patient's general condition was getting
      worse, ECOG performance status 3. In January 2009, the resection of main tumor
      was performed to control abdominal hemorrhage. After the operation, a general
      condition of the patient was getting better, ECOG performance status 1. The
      resection for drug resistant GIST may contribute to improve the patient's quality
      of life.

PMID- 20037421
TI  - [A case of primary retroperitoneal malignant fibrous histiocytoma].
AB  - A 68-year-old man visited our hospital due to constipation. A hard mass was
      palpated in the left side abdomen. Several examinations could point out a large
      left sided retroperitoneal tumor. Because the tumor was adherent to the
      descending colon, both were removed. Based on histological and
      immunohistochemical inspection, the tumor was diagnosed as malignant fibrous
      histocytoma (MFH) on retroperitoneum. No treatment was undergone as the
      postoperative course was good, however, computed tomography (CT) for 8 months
      after the surgery showed the sign of local recurrence. It has been reported that
      the prognosis of MFH was very poor and a surgical resection was the only
      treatment for MFH, or we are expecting to find an effective treatment quickly
      such as a new combined chemotherapy.

PMID- 20037422
TI  - [Two cases of advanced hepatocellular carcinoma with portal vein tumor thrombus
      responding to transcatheter arterial infusion chemotherapy using cisplatin].
AB  - We report two cases of advanced hepatocellular carcinoma( HCC) with a portal vein
      tumor thrombus (PVTT) responding to transcatheter arterial infusion chemotherapy
      (TAI) using cisplatin (CDDP). Case 1: A 65-year-old male patient was diagnosed
      with unresectable multiple HCCs. After 5 courses of transcatheter arterial
      chemoembolization (TACE), the tumor became markedly enlarged, and a PVTT (Vp2)
      and lymph node metastasis were noted. TAI was conducted as the second- line
      chemotherapy, and the liver tumor, PVTT, and lymph node metastasis shrank. The
      clinical response was rated as a partial response (PR). Case 2: A 72-year-old
      female patient was diagnosed with single HCC. After a course of TACE, the tumor
      became markedly enlarged and was accompanied by a PVTT (Vp4). TAI was performed
      as the second-line chemotherapy, and the liver tumor and PVTT significantly
      shrank. The clinical response was also rated as a PR. TAI using CDDP as the
      second-line chemotherapy for advanced HCC is a promising treatment likely to
      contribute to the improvement of the patient's prognosis.

PMID- 20037423
TI  - [A case of glycogen storage disease type I with hepatocellular carcinoma].
AB  - The patient was a 55-year-old female. In 1997, she was diagnosed as type-I
      glycogen storage disease (von Gierke disease). In March 2002, abdominal
      ultrasound tomography revealed an early enhanced lesion at liver S2, which
      suspected to a well differentiated hepatocellular carcinoma (HCC) with super
      paramagnetic iron oxide (SPIO) enhanced magnetic resonance imaging (MRI). From
      2002 to 2006, she received three times trans-arterial chemo-embolization (TACE)
      at enhanced lesions. But abdominal computer tomography (CT) revealed a 3.6 cm-in
      diameter early enhanced lesion near this tumor at S2, which was suspected to a
      diagnosis of recurrent HCC in December 2008. Therefore, she received a partial
      hepatectomy at S2. This resected specimen was diagnosed as poorly differentiated
      HCC. This patient is still alive with no recurrence after 6 months from
      operation. In conclusion, it might be effective for an early detection of
      recurrent HCC to see the doctor for a long regular checkup, because the growth of
      HCC with glycogen storage disease would be very slow.

PMID- 20037424
TI  - [A case of hepatocellular carcinoma with advanced gastric cancer treated by radio
      frequency ablation].
AB  - A 69-year-old male patient has been diagnosed hepatitis B a couple of years ago
      at our hospital. His follow up CT revealed multiple hepatocellular carcinomas
      (HCCs) in May 2007. Transarterialchemoembolization was selected for treatment. A
      couple of months later, carcinoma in segment eight was diagnosed viable by CT.
      Radiofrequency ablation (RFA) therapy was performed for further treatment but was
      incomplete. On the other hand, gastric cancer was discovered at the same time.
      Total gastrectomy with regional lymph node dissection and splenectomy were
      performed. Pathological examination of the dissected lymph nodes revealed not
      only the metastases of the gastric cancer but also HCC. Recently, RFA treatment
      is growing in number for HCC. Although lymph node metastases in HCC are seldom
      seen, our case suggests that RFA may have led to the unexpected metastases to the
      lymph nodes.

PMID- 20037425
TI  - [A case of hemobilia developing after radiofrequency ablation (RFA) for
      hepatocellular carcinoma].
AB  - We report a case of hemobilia developing after RFA for hepatocellular carcinoma.
      A 75-year-old woman with hepatitis C was diagnosed as hepatocellular carcinoma
      (d=15 mm) located in subsegment 7. Laboratory data on admission are AFP 37.3
      ng/mL, PIVKA-II 20 mAU/mL, GOT/GPT 84/52 IU/L, T-Bil 1.1 mg/dL, Alb 3.8 g/dL, Plt
      8.9x104/microL, and PT 11.8 seconds (INR 1.28) "Child classification A". Under
      general anesthesia, percutaneous RFA (Cool-tip radionics 10 minutes) was
      performed. Tumor appeared to be well treated, but on day 5 after the procedure,
      the patient had sudden upper abdominal pain, followed by the elevation of total
      bilirubin conc. (3.3 mg/dL) and decrease of Hb. Abdominal ultrasonography showed
      a debris-like shadow in the gall bladder. Hemobilia was confirmed because
      endoscopic examination revealed blood contaminated bile from the papilla Vater.
      Since spontaneous thrombolysis is known to occur in the bile, the patient was
      only followed by MRI. Symptoms were subsided in a week without any treatment.
      Obstructive jaundice due to hemobilia is a rare complication of RFA, and may be
      followed without any treatment.

PMID- 20037426
TI  - [Radiofrequency ablation combined with transcatheter arterial chemoembolization
      for the local recurrent tumor after resection of the adrenal metastasis from
      hepatocellular carcinoma--a case report].
AB  - We report a case of local recurrent tumor after a resection of right adrenal
      metastasis from hepatocellular carcinoma successfully treated with radiofrequency
      ablation combined with transcatheter arterial chemoembolization. The case is a
      man in his 80s who had a curative surgical resection and microwave coagulation
      therapy (MCT) for multiple hepatocellular carcinomas in February 2003. The
      lesions were judged to be T4, N0, M0 and Stage IV,then, he was treated as an
      outpatient on a regular schedule. In July 2003, a right adrenal tumor 2 cm in
      diameter was detected by computed tomography (CT), but the value of the
      adrenocortical hormones were normal on blood examination, and he was observed at
      regular intervals. In February 2005, the adrenal lesion enlarged to 5 cm in
      diameter and the value of PIVKA-II became high on blood examination, so April
      2005, a surgical resection was performed, and it was diagnosed as the metastasis
      from HCC. In July 2008, the recurrent tumor 3 cm in diameter was observed in the
      right retroperitoneum. It was considered inoperable because of the past
      operation, and transcatheter arterial chemoembolization of an inferior adrenal
      artery and a fine branch through a right sub-phrenic artery was performed for the
      recurrent tumor, and one week after the embolization, radiofrequency ablation was
      treated by CT fluoroscopy guidance. Ten months after the tumor embolization
      combined with radiofrequency ablation, there were no local and distant
      recurrences observed by CT examination. Transcatheter arterial embolization
      combined with radiofrequency ablation is considered as a feasible and effective
      method for not only HCC but also for a local recurrent tumor after resection of
      the adrenal metastasis from hepatocellular carcinoma.

PMID- 20037428
TI  - [A case of hepatitis B-related multiple hepatocellular carcinomas, most of which
      lead to necrosis possibly due to the implantation of an arterial infusion
      catheter].
AB  - The patient was a 59-year-old male with chronic hepatitis type B. He was
      diagnosed as having multiple hepatocellular carcinomas (HCCs), most of which
      showed hypervascular features on contrast-enhanced CT scan. He underwent the
      implantation of a 5-french catheter by" GDA coil method" for hepatic arterial
      infusion of chemotherapy. After the implantation, he suffered from high fever
      with a sharp elevation in transaminase levels. Since his liver function gradually
      deteriorated, he was not able to receive hepatic arterial infusion of
      chemotherapy. However, three weeks after catheter implantation, most of the
      tumors were no longer enhanced on dynamic CT scan, suggesting a loss of tumor
      vascularity, ie, induction of tumor necrosis. It was speculated that necrosis of
      the tumors was caused by the reduction of hepatic arterial blood flow due to the
      catheter placement.

PMID- 20037427
TI  - [A case of successful multimodal treatment for combined hepatocellular and
      cholangiocarcinoma with portal venous tumor thrombus].
AB  - We report a case of successful multimodal treatment for combined hepatocellular
      and cholangiocarcinoma with portal venous tumor thrombus. A 66-year-old man was
      diagnosed with hepatocellular carcinoma with Vp3 by abdominal enhanced CT. He
      underwent a complete tumor resection and following interferon and 5-FU combined
      intra-arterial chemotherapy as an adjuvant setting. The histological findings
      were consistent with combined hepatocellular and cholangiocarcinoma. At 9 months
      after the surgery, lymph node metastases were detected. Then we started an oral
      fluoropyrimidine anticancer agent S-1, because the recurrence was suspected to be
      originated from the cholangiocarcinoma component. Thereafter, sustained partial
      remission was achieved. In case of combined hepatocellular and
      cholangiocarcinoma, we need to create a treatment strategy against
      characteristics of both components.

PMID- 20037429
TI  - [A case report of combined hepatocellular-cholangiocarcinoma whose lymph node
      recurrence effectively treated with UFT].
AB  - Primary liver cancer with lymph node metastasis was recognized as poor prognosis.
      We herein report a case of post operative lymph node recurrence treated with UFT.
      A 74-year-old man with a huge mass lesion in the right liver with para Aortic
      lymph node metastasis admitted our hospital in April 2007. Extended right lobe
      hepatectomy and lymph node dissection were performed in May. A histological
      examination of the resected specimen showed a combined hepatocellular
      cholangiocarcinoma with three lymph node metastasis. Computed
      tomography(CT)revealed intra hepatic metastasis (S3) and right adrenal grand
      metastasis 5 months after surgery. Transarterial embolization (TAE) and right
      adrenalectomy were performed for each metastasis. CT revealed a lymph node
      metastasis at the right side of infra vena cava 1 year after surgery. He was
      treated by oral administration of UFT (200 mg/day). The AFP and PIVKA-II value
      gradually decreased after administration of UFT. The size of lymph node
      metastasis became small confirmed by CT. But the AFP and PIVKA-II value increased
      1 year and 7 months after surgery. TAE was performed against lymph node
      metastasis 1 year and 9 months after surgery. This case suggests UFT is useful
      for suppressing the growth of the lymph node metastasis.

PMID- 20037430
TI  - [A case of complete response to S-1 therapy for multiple pulmonary recurrences of
      hepatocellular carcinoma after hepatic resection].
AB  - A 68-year-old man lost in unconscious and was diagnosed as ruptured
      hepatocellular carcinoma (HCC) in a local emergency hospital. He was treated by
      transcatheter arterial embolization, and further investigation revealed
      simultaneous cancer in rectum. He was referred to our institute, and admitted in
      June 2005. He underwent lateral segment and S8 partial resection of the liver,
      cholecystectomy, anterior resection of rectum, and D3 lymphadenectomy in August
      2005. Multiple HCC recurrences in the remnant liver appeared in December 2005. He
      was subsequently treated with transcatheter chemoembolization four times. In May
      2006, CT scan revealed multiple metastatic nodules in bilateral lungs with
      remarkably elevated serum AFP and PIVKA-II. The nodules were diagnosed as lung
      metastasis of the HCC. Because the lesions grew larger, S-1 was started in
      February 2007. Diagnostic imaging and tumor markers showed a marked improvement 2
      months after S-1 administration, and no recurrence has been found since then.
      This case illustrates that S-1 may be an effective treatment for HCC with
      extrahepatic metastasis.

PMID- 20037431
TI  - [A case of hepatocellular carcinoma which could be diagnosed with Gd-EOB-DTPA
      enhanced MRI].
AB  - The patient was a 75-year-old female. In 2005, abdominal computer tomography (CT)
      revealed a 18 mm-in-diameter early enhanced lesion (tumor A) in S8, which was
      diagnosed as hemangioma of liver with abdominal simple MRI examination. However,
      abdominal computer tomography (CT) revealed a 16 mm-in-diameter early enhanced
      lesion (tumor B) near the tumor A to at S8 in April 2008. Both tumor A and tumor
      B led to a diagnosis of hepatocellular carcinoma (HCC) with Gd-EOB-DTPA enhanced
      magnetic resonance imaging (MRI) (tumor A was suspected to HCC with adipose
      components, and tumor B was suspected to HCC with bile excretion disorder). In
      July 2008, he received S8 partial hepatectomy at these hepatic tumors. In this
      resected specimen, a new lesion was detected as a 7 mm-in-diameter HCC,
      sandwiched in previous two tumors. Previous two tumors were diagnosed as well
      differentiated HCCs and a new lesion was diagnosed as moderately differentiated
      HCC. This patient is still alive with no recurrence after 14 months from
      hepatectomy. In conclusion, Gd-EOB-DTPA enhanced MRI might be useful in diagnosis
      of hepatic tumor characteristics.

PMID- 20037432
TI  - [A long-term survival case of hepatocellular carcinoma with lymph node metastasis
      on the posterior surface of the pancreas head and portal vein tumor thrombus
      successfully treated with hepatopancreatoduodenectomy and adjuvant interferon
      alpha and 5-fluorouracil combination therapy].
AB  - A 72-year-old man, who had undergone partial hepatectomy for hepatocellular
      carcinoma (HCC), was admitted to our hospital for treatment of HCC recurrence. At
      laparotomy, intrahepatic metastasis on S6/1 with lymph node metastasis on the
      posterior surface of the pancreas head, suggesting direct invasion to pancreas,
      and portal vein tumor thrombus were identified. Hepatopancreatoduodenectomy and
      removal of the tumor thrombus was performed. Microscopic examination confirmed
      intrahepatic metastasis from HCC with portal vein tumor thrombus and lymph node
      metastasis. After the surgery, adjuvant interferon-alpha and 5-fluorouracil
      combination therapy was administered. Forty-one months after the surgery,
      solitary intrahepatic recurrence was identified, and radiofrequency ablation
      therapy was performed. Sixty-six months after the surgery, he remains in good
      condition without recurrence. This case suggests that some patients with HCC
      involving lymph node metastasis and portal vein tumor thrombus can gain a long
      term survival by multifocal treatment including curative surgery, even if the
      surgical procedure is highly stressful, and adjuvant interferon-alpha and 5
      fluorouracil combination therapy.

PMID- 20037433
TI  - [A case of adenosquamous carcinoma of the liver].
AB  - A 60-year-old man underwent abdominal computed tomography due to the chest
      pressure. Then, a 10 cm sized tumor in the right lobe of the liver was detected.
      Tumor marker was normal except that CA19-9 was as high as 703 U/mL. We diagnosed
      as the CCC and performed PTPE, and then, we performed right hepatectomy and
      adrenal deprivation, and partial resection of the diaphragm and IVC. Pathological
      diagnosis of the resected specimen was adenosquamous carcinoma of the liver.
      Metastasis to the costal bone was detected after the operation, and irradiation
      was performed. Now, S-1/GEM therapy as adjuvant chemotherapy is administered.
      Adenosquamous carcinoma of the liver is very rare and its prognosis is very poor
      due to local recurrence and metastasis to the lymph node. Adjuvant therapy is
      necessary but a unified guideline is not determined.

PMID- 20037434
TI  - [A case of long-term survival for advanced gallbladder cancer].
AB  - A 50-year-old woman with epigastric uncomfortable feeling was referred to our
      hospital. We have diagnosed her as an advanced gallbladder cancer with direct
      liver invasion and lymph node metastasis of hepatoduodenal ligament by the image
      analysis, including enhanced abdominal CT, MRI and FDG-PET. Subsequently, we
      performed operation with cholecystectomy, hepatic segmentectomy of S4a/5, bile
      duct resection and D2 lymph node dissection, resulted in the curative operation.
      We additionally performed adjuvant chemotherapy with 6 courses of 800 mg/m2 of
      gemcitabine (GEM) on days 1, 8 and 15 for every 35 days. No recurrent signs were
      observed for 33 months after curative operation.

PMID- 20037435
TI  - [A case report of S-1 monotherapy responding to unresectable gallbladder cancer].
AB  - A 68-year-old man was found to have a gallbladder cancer. Curative operation was
      impossible because the gallbladder cancer invaded around the gallbladder in CT on
      15th of April, 2008. S-1 monotherapy (120 mg/day) was started. S-1 was given
      orally twice daily for 4 weeks followed by 2 weeks without a treatment. There was
      no remarkable side effect. The gallbladder cancer was smaller in CT on 25th of
      September, 2008, and we confirmed a partial response (PR) in CT on 13th of
      February, 2009. In a pilot phase II study of S-1 for biliary tract cancer, the
      overall objective response rate was 35.0%. There was no severe side effect. S-1
      is one of the effective drugs for biliary tract cancer.

PMID- 20037436
TI  - [Effects of pharmacokinetic modulation chemotherapy (PMC) using oral UFT and
      venous 5-FU infusion as adjuvant chemotherapy for intrahepatic cholangiocellular
      carcinoma].
AB  - Intrahepatic cholangiocellular carcinoma after curative surgery was treated with
      pharmacokinetic modulation chemotherapy (PMC) as adjuvant chemotherapy. METHOD:
      PMC consists of medication with UFT and intravenous infusion of 5-FU. The dose of
      UFT is 300 mg/day and the infusion of 5-FU is performed with 500 mg/body once a
      week for one year. RESULTS: Twelve cases were treated with PMC (A-group) and
      eight cases were without PMC (B-group). The mean number of 5- FU infusions in all
      cases was 33.2 (6-48). The median survival time (MST) of A-group was 78.9 months,
      and of B-group was 74.3 months. Five-year cumulative survival rates of A-and B
      group were 59.4%, 59%,and disease free survival rates were 37.5%,
      25%,respectively. There was no significance between two groups. CONCLUSION: PMC
      as adjuvant chemotherapy for intrahepatic cholangiocellular carcinoma was not so
      effective in comparison with cases without adjuvant chemotherapy.

PMID- 20037437
TI  - [A case of successful management of recurrent intrahepatic cholangiocarcinoma by
      repeated radiofrequency ablations].
AB  - A 67-year-old man with intrahepatic cholangiocarcinoma (ICC) underwent an
      extended right hepatectomy. Approximately, during the next 20 months after the
      operation, the patient underwent 6 times of radiofrequency ablation for solitary
      recurrence of ICC. He has survived for 26 months after hepatic resection with PS
      0. Radiofrequency ablation for solitary recurrence of ICC may be effective for a
      good prognosis.

PMID- 20037438
TI  - [A case of surgical treatment of solitary liver metastasis from pancreatic
      cancer].
AB  - We report a 50-year-old female with pancreatic cancer invading the duodenum. In
      December 2006, the patient underwent the pancreatoduodenectomy with portal vein
      resection. Histological examination demonstrated a poorly differentiated ductal
      carcinoma fT4N2M0, fStage IVb. The postoperative irradiation to pancreatic bed
      was performed one month after surgery, followed by an adjuvant chemotherapy using
      gemcitabine. Eight months post operation, CT examination showed liver and lung
      metastases, resulting in conversion of the drug to S-1. S-1 administration was
      withdrawn because of grade 3 vomiting. Paclitaxel was selected as the third-line.
      However, febrile neutrophenia and septic shock were emerged during the first
      course and recovered by the cause intensive care. CT revealed disappearance of
      recurrence during 7 months without any chemotherapy. Thereafter, the solitary
      liver metastasis reappeared without any other hot spot on PET. Resection of liver
      metastasis resulted in survival of 29 months after pancreactomy, and 8 months
      after liver resection.

PMID- 20037439
TI  - [Repeated resections of asynchronous liver metastases after pancreatomy for
      pancreatic cancer--a case report].
AB  - The prognosis of pancreatic cancer is most dismal in all gastrointestinal
      cancers, because the patients with pancreatic cancer are vulnerable for
      recurrence such as local relapse and liver metastasis even after a complete
      surgical resection. We herein report a case of pancreatic cancer, which underwent
      resection of local relapse and multiresections of liver metastases, resulting in
      a relatively longer survival. A 71-year-old woman was referred to our hospital
      for a local recurrence in the tail of the pancreas in October 2006, 17 months
      after the first distal pancreatectomy. A second distal pancreatectomy was
      curatively performed on this patient. After the second surgery, sequent solitary
      liver metastases appeared, and we then performed partial hepatectomies repeatedly
      in August 2007, December 2007 and December 2008. The histopathological findings
      of each specimen from the resected liver showed tubular adenocarcinoma, same as
      the original pancreatic tumor obtained from the first surgery. Although
      chemotherapy was not permitted due to gemcitabine-induced interstitial
      pneumonitis, the patient is still alive over 4 years after the first operation
      under palliative care. This study discusses a controversial issue about the
      resection of the liver metastases from pancreatic cancer, along with the
      necessity for careful selection of the patients before attempting the operation.

PMID- 20037440
TI  - [A case of epidermoid cyst in the intrapancreatic accessory spleen mimicking
      pancreatic malignant tumor].
AB  - We report a rare case of an epidermoid cyst in the intrapancreatic accessory
      spleen with producing CA19-9. A 42-year-old woman was referred to department of
      internal medicine of our hospital due to growing cystic lesion at the pancreatic
      tail. Laboratory tests on admission revealed a high serum CA19-9 (102.0 U/mL).
      Ultrasound sonography detected a 25-mm monolocular cystic tumor with thick
      capsule and septum. The capsule and septum was enhanced on computed tomography.
      Endoscopic examination of upper gastrointestinal tract and colon revealed normal.
      CA19-9 was elevated up to 147.3 U/mL after 2-month follow-up, and she was
      referred to department of digestive surgery. We suspected a mucinous cystic
      neoplasm or endocrine tumor, and distal pancreatectomy was performed. The
      surgical specimen showed a septate cyst surrounded by brown solid tissue
      resembling normal spleen. The patient was discharged on postoperative day 11.
      Histological diagnosis was an epidermoid cyst originated from an intrapancreatic
      accessory spleen. Immunohistochemical analysis of CA19-9 in the epidermoid cyst
      showed clear staining of the inner epithelium of the cyst. The serum CA19-9 value
      was confirmed to decline to normal 1 month after resection.

PMID- 20037441
TI  - [The effectiveness of reduction surgery and gemcitabine for multiple bowel
      obstructions due to peritoneal dissemination of pancreatic carcinoma with liver
      metastasis--a case report].
AB  - A 62-year-old woman visited our hospital because of the increasing lower left
      abdominal distention. Computed tomography (CT) revealed pancreatic carcinoma
      invading to spleen with liver metastasis and peritoneal dissemination. Soon
      after, the patient showed a severe bowel obstruction symptom, so we performed an
      emergency operation. The pancreatic carcinoma was located at the tail of pancreas
      invading to spleen with liver metastasis. Due to peritoneal dissemination, severe
      stenosis and dilatation of the small intestine, stenosis of the ascending and
      sigmoid colon was admitted. We performed a distal pancreatectomy, partial
      hepatectomy, partial resection of the stomach, five-partial resection of the
      small intestine, right colectomy and sigmoidectomy. No operative complication was
      seen, and we started chemotherapy using gemcitabine soon after the operation.
      After 3 months, the tumor markers normalized. She was able to finish intestinal
      nutrition 8 months after the operation. At present (20 months after the
      operation), the patient is still alive with good performance status (PS 0). The
      removal of bowel obstruction by operation enabled us to perform intestinal
      nutrition and sufficient chemotherapy, which may lead to the favorable prognosis.

PMID- 20037442
TI  - [A long-term survival case of pancreatic cancer with hepatic metastasis after
      pancreaticoduodenectomy successfully treated by s-1 and gemcitabine combination
      chemotherapy].
AB  - Gemcitabine monotherapy is accepted as a standard first-line treatment for
      locally advanced unresectable or metastatic pancreatic cancer. On another front,
      S-1 and gemcitabine combination chemotherapy is challenging but promising. We
      report a long-term survival case of pancreatic cancer with hepatic metastasis
      after surgical resection treated by S-1 and gemcitabine combination chemotherapy.
      A 59-year-old woman was diagnosed as locoregionally advanced pancreas head cancer
      without metastatic disease. Pancreatoduodenectomy with regional lymph node
      dissection was performed after preoperative chemoradiotherapy. Pathological
      examination revealed a poorly differentiated adenocarcinoma. A solitary hepatic
      metastasis was detected by CT imaging one year after the surgery. The patient
      received 35 courses of S-1 and gemcitabine combination therapy. The metastatic
      tumor was disappeared, and serum CEA decreased to a normal level. S-1 and
      gemcitabine combination therapy is not only effective but also well tolerated and
      safe. This combination therapy should be considered one of selective choices for
      advanced or metastatic pancreatic cancer.

PMID- 20037443
TI  - [A partial response to S-1 as second-line chemotherapy in a patient with
      unresectable pancreatic cancer].
AB  - A male in his fifties presented with a primary complaint of abdominal distension
      and appetite loss. CT revealed a primary pancreatic tumor with massive ascites.
      The patient was treated with gemcitabine as the first-line chemotherapy.
      Gemcitabine (1,000 mg/m2) was intravenously administered 3 times (on days 1, 8,
      15) every 4 weeks (days 1-28) as 1 course. CT revealed the size of the primary
      tumor to decrease and no ascites were observed. A new abdominal lesion appeared
      after 11 courses of gemcitabine. The time to progression was 11 months after the
      first-line chemotherapy. The patient was then treated with S-1 as second-line
      chemotherapy. S-1 (80 mg/m2) was orally administered daily for 4 weeks (days 1-
      28) every 6 weeks. CT thereafter revealed a partial response. The patient
      experienced no adverse events. The time to progression was 6 months after
      starting the second-line chemotherapy. Gemcitabine is the standard regimen for
      unresectable pancreatic cancer. However, the benefits of second-line chemotherapy
      remain unclear. S-1 has been reported to show a considerable efficacy, achieving
      a response rate of 37.5% in chemo-naive patients with pancreatic cancer. S-1 is
      therefore considered to be promising as second-line chemotherapy for unresectable
      pancreatic cancer, due to the fact that a considerable survival benefit has been
      observed for patients with unresectable pancreatic cancer.

PMID- 20037444
TI  - [A case report of un-resectable pancreas body carcinoma successfully treated by
      chemoradiotherapy].
AB  - We report a case of unresectable pancreatic cancer who survived for 29 months
      after a successful treatment by concurrent chemo-radiotherapy by gemcitabine and
      systemic administration of gemcitabine. A 65-year-old woman who was diagnosed as
      unresectable pancreas body cancer received concurrent chemo (gemcitabine 800
      mg/body/w) -radiotherapy (1.8x30 Gy) and systemic chemotherapy (gemcitabine 1,000
      mg/body/w) at an outpatient clinic. Twenty nine months after the initial
      treatment, she was died of peritoneal dissemination. Recently, there are some
      reports of synergistic effect for combined treatment of gemcitabine and
      radiation. Clinical course of our case supports the synergistic effect of
      radiation and gemcitabine.

PMID- 20037445
TI  - [A case of locally advanced pancreatic cancer with superior membrane artery
      invasion successfully resected after gemcitabine-based chemoradiotherapy].
AB  - A 69-year-old man with chief complaint of epigastralgia was diagnosed as locally
      advanced borderline unresectable pancreatic head cancer that involved superior
      membrane artery (SMA). Gemcitabine (GEM) -based chemoradiotherapy (CRT) was
      administered for consecutive 3 weeks in the following fashion: continuous twice-a
      day accelerated radiotherapy (2 daily fractions of 1.5 Gy, 5 days a week, with a
      6-hr minimal interval between fractions) with 3-time weekly intravenous infusions
      of GEM. Total radiation dose was 45 Gy and GEM was given on days 1, 8 and 15 at
      dose of 800 mg/m2. After the completion of CRT, the involvement of SMA remained.
      Next, additional systemic chemotherapy with GEM was performed for 3 weeks in the
      following fashion: weekly intravenous infusions of GEM at dose of 1,000 mg/m2.
      Finally, the main tumor and the invasion to SMA were reduced. Surgical resection
      with negative margins (R0 resection) was performed. Adjuvant chemotherapy with 6
      courses of GEM was also performed. The patient has no recurrence, suggesting the
      efficacy of GEM-based CRT for locally advanced borderline unresectable pancreatic
      cancer.

PMID- 20037446
TI  - [A case report-neoadjuvant chemoradiotherapy with combination of S-1 and
      gemcitabine in a patient with locally advanced pancreatic cancer].
AB  - A 63-year-old woman was pointed out pancreatic tumor by a follow up CT after
      operation for the corpus uteri cancer. She was diagnosed as having locally
      advanced pancreatic cancer which involved the superior mesenteric vein (SMV). She
      was treated with radiation (1.8 Gyx28 Fr) and the combination chemotherapy of S-1
      plus gemcitabine (S-1: 80 mg/m2/dayx28 days, gemcitabine 200 mg/m2/dayx6 fr, 1 fr
      a week). Indeed, grade 3 leukopenia and neutropenia were occurred by this
      treatment, she could be treated on schedule. Four weeks later from completion
      date, a reduction of the tumor size and an improvement of involving SMV were
      observed by diagnostic imaging. Subsequently, pylorus-preserving
      pancreatoduodenectomy (PpPD) with a partial resection of SMV and intraoperative
      radiation were undergone. She was discharged 19 days after the operation without
      any surgical complications, and is undergoing adjuvant chemotherapy.

PMID- 20037447
TI  - [A case of postoperative brain metastasis originated from pancreatic cancer which
      was successfully treated by resection and postoperative irradiation].
AB  - We report a case of metastatic brain tumor originated from pancreatic cancer,
      which might be clinically considered as rare and has been reported as a
      remarkably poor-prognostic disease. A 64-year-old male underwent pancreas tail
      resection for pancreatic cancer (R0 resection). Histological study revealed an
      invasive ductal carcinoma (T4N2M0, fStage IVb). Following a short term of GEM
      administration, S-1 (80 mg/m2,day 1-28/42 days) was administered as the second
      line. After 7 courses of S-1 chemotherapy, a follow-up CT demonstrated lymph node
      recurrence in cervical and mediastinum region. S-1 administration was stopped and
      irradiation to these sites (60 Gy) resulted in PR. Two months after irradiation,
      dizziness and speech disturbance appeared, and MRI examination demonstrated a
      solitary brain metastasis, which was removed because of rapid worseness of
      neurological symptoms. Postoperatively, hemicereberal irradiation (30 Gy) was
      performed. After the brain surgery, no brain metastasis was appeared. The patient
      was alive with abdominal lymph node recurrence for 22 months after distal
      pancreatectomy. It was concluded from these findings that irradiation to systemic
      recurrence originated from pancreatic cancer might be effective as well as
      chemotherapy.

PMID- 20037448
TI  - [A case of stage IV advanced esophageal cancer with a long term survival by
      radiation therapy combined with nedaplatin and 5-FU chemotherapy].
AB  - The patient was a 73-year-old man who complained of dysphagea. Various
      examinations revealed an esophageal cancer with direct invasion to the left main
      bronchus (cT4, N2 (104R, 106recR), M0, Stage IVa) and gastric cancer (cT2, N0,
      M0, Stage IB). The patient was given preoperative chemoradiotherapy (40 Gy/20 fr
      with CDGP 10 mg/body day 1-5, 8- 12, 15-19 and 5-FU 250 mg/body day 1-5, 8-12, 15
      19). After the chemoradiotherapy, we estimated that the esophageal cancer was
      down stage (cT4-->T3), and that a curative operation was possible. Therefore,
      subtotal esophagectomy and partial gastrectomy were performed without a
      complication. Pathological therapeutic evaluation of the esophageal cancer was
      complete response (CR) and the gastric cancer was T2, N0. Adjuvant chemotherapy
      was undergone with S-1. However, two years after the first operation, we found a
      recurrence of gastric duct. Therefore a surgical resection for recurrence of
      gastric duct was performed. The patient is still alive without recurrence 5 years
      and 2 months after the first treatment. Radiation therapy combined with
      nedaplatin and 5-FU is a safe and effective method for treating cT4 advanced
      esophageal cancer.

PMID- 20037449
TI  - [A case of esophageal cancer associated with colon cancer successfully treated
      with combination chemotherapy of FOLFOX and concurrent radiotherapy].
AB  - The standard chemotherapy regimen for esophageal cancer is cisplatin and 5
      fluorouracil (5-FU). We herein report a case of esophageal cancer associated with
      colon cancer, which was treated with combination chemotherapy of FOLFOX. The
      patient received chemotherapy of modified FOLFOX6 (mFOLFOX6) at dosages of 80% of
      standard regimen (oxaliplatin 68 mg/m2, levofolinate calcium 160 mg/m2, bolus 5
      FU 320 mg/m2, and followed by continuous 5-FU 1,920 mg/m2/ 46 hr) in combination
      with radiotherapy (total 61.6 Gy). He developed grade 3 leukopenia after 2
      courses of mFOLFOX6 and the 3rd course was started at dosages of 70% of standard
      regimen with 1 week delay. After that, no other adverse event without grade 2
      esophagitis was appeared. Esophagogram revealed a partial response in primary
      tumor of the esophagus after 3 courses of chemotherapy with radiotherapy and
      blood chemistry examination showed negative squamous cell carcinoma antigen. One
      month after chemoradiotherapy, esophagogram revealed tracheoesophageal fistula,
      but tumor of the esophagus was well controlled. FOLFOX regimen combined with
      radiotherapy is well tolerated and effective for inoperable esophageal cancer.
      FOLFOX cannot be used for esophageal cancer in Japan, so clinical trial of FOLFOX
      for esophageal cancer should be conducted in the near future in Japan.

PMID- 20037450
TI  - [A case of advanced esophageal cancer that has come back eight years after
      combined modality therapy].
AB  - The case is for a woman of 77 years old. In February 1992, right thoracotomy
      subtotal thoracic esophagectomy was performed after performing preoperative
      chemotherapy (FP therapy) for advanced esophageal cancer for two courses. The
      pathological diagnosis was Mt, mod. diff. sqcc, mp, n4 (#2: 1/13, #9: 3/4), ly2,
      v0, stage IVa. As a postoperative adjuvant therapy, FP therapy was performed for
      two courses and we took a wait-and-see approach as an outpatient since then. As
      we found lymph node metastasis surrounding the root of celiac artery and right
      renal vein by an abdominal CT in October 1999, nedaplatin+5-FU therapy was
      performed for 5 courses/24 weeks as second-line chemotherapy, and furthermore, a
      radiation therapy, linac 50 Gy was performed. The involved lymph node was reduced
      and the therapy evaluation was CR. After that, a home-healthcare period of about
      six months was obtained. We have experienced a case of advanced esophageal cancer
      that has come back eight years after combined modality therapy, and after that,
      the patient could obtain a long-term survival with a marked effect of
      chemotherapy.

PMID- 20037451
TI  - [A case of mediastinoscope-assisted transhiatal esophagectomy for thoracic
      esophageal cancer after radical operation for lung cancer].
AB  - We herein report a case of thoracic esophageal cancer operated on by
      mediastinoscope-assisted transhiatal esophagectomy after a right upper lobectomy
      for primary lung cancer. A 70-year-old male with non-small-cell lung cancer
      (T4N2M0, cStage III B) underwent chemo-radiation therapy followed by an upper
      lobectomy of the right lung with mediastinal lymph node dissection. The lung
      cancer histologically showed complete remission (CR), and no recurrence has been
      shown. Five years after the operation of lung cancer, esophageal cancer (T3N0M0,
      cStage II) was endoscopically detected in this patient. Partial remission was
      obtained after neoadjuvant FP chemotherapy for esophageal cancer. Therefore,
      mediastinoscope-assisted transhiatal esophagectomy was performed in consideration
      of a history of a right thoracotomy and of pulmonary dysfunction. Preventive
      tracheostomy was performed because of recurrent nerve paralysis, but no other
      severe postoperative complication has developed in this case. Histopathological
      findings showed a well differentiated squamous cell carcinoma (pT3 (Ad), pN0, M0,
      pStage II), with involvement at resection margin. He was alive for 11 months
      after the operation for esophageal cancer, although a local recurrence was
      observed. There are still many problems remained of the treatment for esophageal
      cancer patients who had previously undergone a radical operation for lung cancer.
      However, mediastinoscope-assisted transhiatal esophagectomy may become a
      procedure for surgical approach if it seems to be difficult to approach the
      esophageal cancer by thoracotomy again.

PMID- 20037452
TI  - [Surgically resected local recurrence after endoscopic submucosal dissection of
      esophageal cancer--a case report].
AB  - We report a case of surgically resected esophageal cancer which was locally
      recurred after endoscopic submucosal dissection. A 66-year-old man was admitted
      to our hospital because of further examination and a treatment of superficial
      esophageal cancer. A type 0-IIb+IIa cancer occupying the whole circumference of
      the lumen of the middle to lower esophagus was revealed. The depth of the
      invasion was judged to be T1a-EP or LPM by endoscopic ultrasonography, and no
      metastasis to other organs or lymph nodes was detected. Endoscopic submucosal
      dissection (ESD) was performed. However, macroscopic residual cancer didn't seem
      to exist. Pathological diagnosis was squamous cell carcinoma, moderately
      differentiated, the depth of tumor invasion was T1a-LPM. The presence of the
      residual cancer of the horizontal cut margin could not be judged because en bloc
      resection could not be achieved. After that, endoscopic balloon dilatation of the
      esophageal stenosis was performed repeatedly for about one year. Then, he was
      diagnosed as the local recurrence of the squamous cell carcinoma of the
      esophagus. Thoraco-abdominal esophagectomy reconstructed by stomach tube via a
      retrosternal route was undergone. The final stage of the lesion was judged T3N1M0
      (Stage III, UICC) by the histological examination from the resected specimen.
      After the operation, he is receiving adjuvant chemotherapy and alive without
      recurrence. When endoscopic resection of the esophageal cancer is performed to
      the lesion, which relatively indicated to endoscopic resection or outside the
      guideline criteria for endoscopic resection, it is important that we choose the
      appropriate treatment protocol obtaining an informed consent from the patient
      sufficiently.

PMID- 20037453
TI  - [A case of advanced esophageal cancer with para-aortic lymph node metastasis with
      complete response (CR) to combination chemotherapy including nedaplatin].
AB  - The patient was a 55-year-old male, who was diagnosed to have a middle thoracic
      esophageal squamous cell carcinoma with para-aortic lymph node metastasis. The
      clinical stage diagnosis was T3N4M1, stage IVb, non-resectable esophageal SCC.
      Systemic chemotherapy with low-dose nedaplatin/5-FU treatment was started as the
      initial treatment. After three courses, para-aortic lymph node metastasis was not
      found by CT scan, and we added radiation therapy. After radiation therapy by 45
      Gy, primary lesion and mediasternal lymph node metastasis were not shown by
      endoscopy and CT scan. We detected an increase of tumor marker after the
      observation for six months without any treatment, and then we started
      docetaxel/nedaplatin treatment as secondary chemotherapy. After ten courses, the
      tumor marker was decreased, and the patient is still in a stable disease state.
      We concluded that FGP therapy and DGP therapy were a very effective treatment for
      advanced esophageal SCC.

PMID- 20037454
TI  - [Assessment of esophageal cancer with remote metastases treated with
      multidisciplinary therapy].
AB  - We present three cases of patients diagnosed with esophageal cancer with distant
      metastases. We conducted chemotherapy, radiotherapy, RFA, and operation for main
      tumor and lymph node, lung, brain metastasis. They were for a long-term survival
      with multidisciplinary therapy. The longest survival time was about three years.
      We discussed our cases in light of review of the literature.

PMID- 20037455
TI  - [Radiofrequency ablation for postoperative recurrent of metastatic lesions of
      esophageal cancer].
AB  - Radiofrequency ablation (RFA) was performed for the postoperative recurrent of
      metastatic lesions of esophageal cancer in 6 patients. All patients were males,
      and the median age was 59. Surgical curativities were A (3 cases), B (2) and C
      (1). The recurrent sites were intramediastinal omentum of gastric tube (2 cases),
      rt lung (2), rt adrenal grand (1) and liver (1). Four cases had a single
      recurrent lesion and the two had multiple lesions consisted of a single lesion as
      RFA target, and the lesions in a different site that were simultaneously treated
      by other therapeutic modalities. The median time of recurrence was 12 months
      after esophagectomy. RFA was performed once in the 3 cases, and twice in the
      other 3 cases. Therapeutic effect evaluated by CT was CR (2 cases), PR (3) and SD
      (1). No serious complications associated with RFA procedure were observed. Three
      patients died due to cancer recurrence within 7 months after RFA. However, RFA
      treated lesions were well controlled to the end. RFA are safe and minimally
      invasive, thus, can be repeatedly performed technique that can induce a good
      local control of the target lesion equivalent to surgical resection. RFA is
      applicable as an effective local therapy for the recurrent or metastatic lesions
      of esophageal cancer.

PMID- 20037456
TI  - [A case of postoperative liver metastasis of esophageal cancer remains in
      progression free after successfully resected].
AB  - A 59-year-old man admitted for upper gastrointestinal endoscopy of the health
      examination in the middle of October 2005 was diagnosed with advanced lower
      esophageal cancer. After a precise examination, he received a subtotal
      esophagectomy followed by three-field lymphadenectomy in the beginning of
      November 2005. The histopathological diagnosis was well differentiated squamous
      cell carcinoma (pT3, ie (+), ly2, v2, pIM0, pN3, pStage III). After two courses
      of systemic chemotherapy so called FP therapy, solitary liver metastasis in S8
      area was detected in May 2007. He received additional two courses of FP
      chemotherapy, but the CT scan revealed that the lesion was progress disease (PD)
      in December 2007. It seemed to be difficult to reduce the tumor progression by
      systemic chemotherapy, so S8 semi-segmental lobectomy was performed. After the
      operation, the patient received the combination chemotherapy with docetaxel and
      nedaplatin once a week on day 1 for 4 weeks in five courses, but the CT scan
      revealed the appearance of the recurrence of residual liver and abdominal
      lymphnodes in January 2009. So a right hepatic lobectomy and lymphadenectomy were
      performed. The patient also received chemoradiotherapy after the operation, no
      recurrence of the liver and lymphnodes metastases has been shown. Surgical
      resection was sometimes seemed to be effective for treating liver metastasis of
      esophageal cancer, thus indication of operation need to be discussed for
      accumulation of many liver metastasis of esophageal cancer.

PMID- 20037457
TI  - [The transition of therapy for recurrent esophageal cancer by PET-CT].
AB  - In our institute, we introduced PET-CT examination as the preoperative and
      postoperative screening for esophageal cancer patients in April 2006. During two
      years before the introduction of PET-CT examination, we performed an intensive
      local control therapy (operation, RFA, definitive chemoradiotherapy) to 13 cases
      with single region recurrence (including 5 cases of cervical lymph nodes
      recurrence, 5 of local recurrence, 3 of distant metastatic recurrence). On the
      other hand, we performed an intensive local control therapy to 21 cases
      (including 4 cases of cervical lymph nodes recurrence, 10 of local recurrence,
      and 7 of distant metastatic recurrence) during two years after the introduction
      of PET-CT examination. In any pattern, there was a tendency of improvement in the
      prognosis of recurrent esophageal cancer patients. These results raised the
      possibility that PET-CT examination was useful for an early detection of the
      recurrent lesions in postoperative follow-up for esophageal cancer patients. And
      there might be a chance of curability in patients with single region recurrence
      by the early detection.

PMID- 20037458
TI  - [Diffusion-weighted MR imaging for postoperative nodal recurrence of esophageal
      squamous cell cancer in comparison with FDG-PET].
AB  - We evaluated the power of DWIBS in patients with postoperative lymph node
      recurrence of esophageal cancer and compared with FDG-PET findings. Forty-seven
      suspected lesions by MDCT were enrolled. No significant difference between DWIBS
      and PET was observed in sensitivity (95% vs 97%), PPV (83% vs 90%) and overall
      accuracy rate (81% vs 87%). The ADCs (x10(-3) mm2/s) of recurrent nodes, primary
      cancer and normal esophagus were 1.124, 1.058 and 2.079, respectively. ADCs of
      recurrent nodes were significantly lower than those of normal esophagus
      (p<0.0001). The cut-off ADC line of 1.5 revealed 100% overall accuracy for
      separating the recurrent lesion from normal esophagus. Noninvasive DWIBS may
      become a valid modality to discriminate nodal recurrence of esophageal cancer by
      no means inferior to PET.

PMID- 20037459
TI  - [A case of bilateral breast cancer and metastatic gastric cancer with peritonitis
      carcinomatosa successfully treated with a combination therapy of S-1 and
      paclitaxel].
AB  - A 46-year-old woman was diagnosed with complaints of bilateral breast tumor with
      massive ascites retention. The patient was examined as scirrhous carcinoma by
      lacteal gland inspection and dysplastic cell by ascites cytotechnology. We
      diagnosed her case to be bilateral breast cancer with peritonitis carcinomatosa,
      lymph node metastases and bony metastases. In addition to that, gastric
      metastasis was diagnosed by the result of widespread irregular gastric mucosa,
      which was inspected through upper gastrointestinal endoscope. The patient was
      treated with S-1 and paclitaxel and has achieved a remarkable response. The
      patient's tumor, gastric metastasis, and ascites were disappeared almost
      completely.

PMID- 20037460
TI  - [A case of stage IV breast cancer responding to S-1 therapy after FEC and PTX
      therapies].
AB  - In November 2005, a 34-year-old female presented to our department with a
      bleeding tumor on her right breast. She noticed the tumor approximately two years
      ago but she left it untreated. An exposed tumor was observed with a diameter of
      approximately 8 cm located in the right breast. It was diagnosed as invasive
      ductal carcinoma by biopsy (ER (+), PgR (+), and HERS2: 1 +). The imaging showed
      multiple metastases to the bilateral lungs, right axillary lymph node,
      mediastinal lymph node and sternal. The diagnosis was made as right breast cancer
      (T4c, N3c, M1, and stage IV). The patient received 4 courses of FEC therapy and 4
      courses of PTX therapy. The patient had a partial response (PR). However, tumor
      markers were elevated in September 2006. Thus, an administration of S-1 was
      initiated. The size of the tumor shown in the imaging was reduced, and the
      patient had a PR. Since December 2008, tumor markers have been elevated again.
      However, the patient has had SD in the imaging and S-1 administrations have been
      continued. A total of 24 courses have been performed to the present time, and the
      patient's conditions have not been aggravated in approximately 3 years and 5
      months. She has maintained a good QOL and is being followed up on an outpatient
      basis. S-1 administrations can be an effective treatment for advanced breast
      cancer resistant to anthracycline and taxane when considering a satisfactory QOL
      of patients.

PMID- 20037461
TI  - [A case of inflammatory breast cancer responding to anastrozole].
AB  - A case is 61 years old woman. In February 2008, she was aware of swelling, skin
      redness and edema in her left breast and visited our hospital. We diagnosed it as
      inflammatory breast cancer with positive hormone receptor (ER+, PgR+) and
      unexpression of HER2 (HercepTest 1 +). We started preoperative chemotherapy with
      weekly paclitaxel followed by FEC100, but we canceled chemotherapy because she
      developed cerebral infarction when we administered paclitaxel twice. Then,
      hormonotherapy using anastrozole (Arimidex) was therefore attempted. Three months
      later, treatment with anastrozole alone reduced the swelling, skin redness and
      edema in her left breast. After eight months of administration, the breast
      swelling, skin redness and edema were completely disappeared. MRI revealed the
      disappearance of the enhanced area. Then mastectomy with auxiliary dissection was
      performed.

PMID- 20037462
TI  - [A successful case of advanced breast cancer of the elderly treated with the only
      breast-hormone therapy as PST].
AB  - An 83-year-old postmenopausal woman was referred to our hospital in order to get
      the treatment for ER positive advanced breast cancer (T4aN2M0, stage III b). The
      patient was diagnosed as the dissected aortic aneurysm and the hypertension. It
      was decided that an operation and chemotherapy would be too difficult with high
      existing risks. As a result, she was treated with anastrozole of PST, a 3rd
      generation aromatase inhibitor, which led to the marked regression of the left
      breast cancer within a month. The cancer wasn't visualized after eighteen months.
      With the ongoing breast-hormone Therapy, no remote metastasis has been found
      after thirty months to this day. The patient hasn't experienced any adverse
      effects with the above-mentioned therapy. We concluded that the hormone
      (anastrozole) therapy as PST is a useful treatment for elderly postmenopausal
      woman with ER positive advanced breast cancer.

PMID- 20037463
TI  - [A case of advanced breast cancer with skin ulceration successfully treated with
      paclitaxel and toremifene therapy].
AB  - We report a case of advanced breast cancer with skin ulceration and bleeding
      (T4bN3bM0, Stage IIIC) achieving a significant improvement of QOL by paclitaxel
      (PTX) and toremifene (TOR) therapy. The patient was a 31-year-old woman who had
      ulcerative breast lump with skin ulcer. A core needle biopsy for breast tumor led
      to a diagnosis of an invasive ductal carcinoma positive for estrogen receptor and
      progesterone receptor, and negative for HER2/neu protein expression. She received
      4 courses of tri-weekly CEF (C: 500 mg, E: 60 mg, F: 500 mg/m2/tri-weekly) and 4
      courses of weekly PTX (80 mg/m2) with TOR (120 mg/day). The bleeding from the
      tumor disappeared after CEF chemotherapy. The response for breast tumor after PTX
      and TOR therapy was evaluated as partial response, and the infraclavicular,
      subpectoral, and interpectoral lymph nodes metastasis disappeared. Muscle
      preserving radical mastectomy (Bt+Ax: Auchincloss) without skin transplantation
      were performed. She had no recurrence during one year after operation. PTX and
      TOR therapy were effective for advanced breast tumor, and can improve patient QOL
      and the clinical outcomes in Stage IIIC advanced breast cancer.

PMID- 20037464
TI  - [A case of giant breast cancer performed a radical excision after neoadjuvant
      chemotherapy].
AB  - The patient was a 79-year-old woman with the giant breast cancer accompanied with
      the invasion to pectoralis major muscle and skin. We worried that we would need a
      skin grafting for the operation because of a wide skin defect. So we performed
      FEC regimen (a combination of epirubicin, cyclophosphamide and 5-FU) as
      neoadjuvant chemotherapy (NAC) to reduce the tumor size. Adverse reaction were
      stomatitis of grade 2 and leukocytopenia of grade 3. The tumor size was reduced
      by about 25% and tumor marker decreased after 6-cycle of NAC. Then we performed a
      radical operation (Bt+Ax with partial resection of invaded part of pectoralis
      major muscle). It was simply difficult to close the skin, but we could close it
      without skin grafting by sliding BD area and axial skin flap. The pathological
      examination of resected specimens revealed scirrhous carcinoma with invasion to
      pectoralis major and skin, but no cancer cell was seen on the excised margin.
      There was no lymph node involvement. Her postoperative course was uneventful. On
      the 17th POD, she went back to her home and she now has been taking paclitaxel
      weekly as adjuvant chemotherapy at an outpatient clinic.

PMID- 20037465
TI  - [A case of advanced breast carcinoma with local hemorrhage during a control of
      hyperthyroidism].
AB  - A CASE: A 55-year-old woman. Around the year 2006, the right breast lump was
      found by palpating. The pain also appeared in 2008, too, and confirmed that it
      appeared to have a tendency to increase. A medical check-up was done and
      diagnosed as T4b, N0, M0, stage IIIB of the breast cancer by a close inspection.
      We noted hyperthyroidism in March 2008. We treated it with internal medicine, but
      we could not control it. We waited for a thyroid function to be normalized. Then
      we were to perform a surgery. In January 2009, we observed a bleeding from the
      part of the breast cancer. We controlled the thyroid function by internal
      medicine. Then we performed a pectoralis muscle preservation breast surgery and
      dermanaplasty with a shortest anesthesia time in order to control the infestation
      to be minimal. It was very likely that we caused a heart failure when a major
      infestation such as general anesthesia in the case of a patient with
      hyperthyroidism. Because we were able to control the hyperthyroidism this time
      and a thyroid function to be stabilized for a local advanced breast carcinoma
      with the hemorrhage temporarily, and were able to operate for the breast cancer,
      as we reported it in this study.

PMID- 20037466
TI  - Target validation using Phase 0 clinical trials: Promises and pitfalls.

PMID- 20037467
TI  - The physical space of science: the Neurosciences Institute and Skirkanich Hall.
AB  - This is the first in a series of articles that Landes Bioscience will publish
      about the physical space where research takes place-the laboratories and
      classrooms where the science you read about in our journals is happening. Here we
      interviewed New York-based architects Tod Williams and Billie Tsien about two of
      their projects, The Neurosciences Institute in La Jolla and Skirkanich Hall at
      the University of Pennsylvania. We asked them, among other things, how they
      engaged scientists in the design process. Here is their response.

PMID- 20037469
TI  - Cutting to the base: Identifying regulators of adventitious rooting.
AB  - Adventitious roots are distinct from primary and lateral roots in that
      adventitious roots develop ectopically from aboveground organs. Whole-genome
      microarrays in poplar provided the first glimpse into the gene networks that are
      remodeled in cells prior to the development of adventitious roots. In the first
      24 hr after removal of stem cuttings, over one-half of the transcripts encoded in
      the genome showed evidence of differential abundance in the cells that will
      eventually give rise to adventitious roots. Major processes that were regulated
      appear related to physiological adaptation of the cutting to acute loss of water
      and nutrients as well as hormone signaling. Comparative transcriptome analysis of
      genotypes that differ in their competence to form adventitious roots may be a
      generally useful strategy to identify genes that regulate adventitious rooting
      efficiency.

PMID- 20037468
TI  - Cytosolic calcium and pH signaling in plants under salinity stress.
AB  - Calcium is one of the essential nutrients for growth and development of plants.
      It is an important component of various structures in cell wall and membranes.
      Besides some fundamental roles under normal condition, calcium functions as a
      major secondary-messenger molecule in plants under different developmental cues
      and various stress conditions including salinity stress. Also changes in
      cytosolic pH, pH(cyt), either individually, or in coordination with changes in
      cytosolic Ca(2+) concentration, [Ca(2+)](cyt), evoke a wide range of cellular
      functions in plants including signal transduction in plant-defense responses
      against stresses. It is believed that salinity stress, like other stresses, is
      perceived at cell membrane, either extra cellular or intracellular, which then
      triggers an intracellular-signaling cascade including the generation of secondary
      messenger molecules like Ca(2+) and protons. The variety and complexity of Ca(2+)
      and pH signaling result from the nature of the stresses as well as the tolerance
      level of the plant species against that specific stress. The nature of changes in
      [Ca(2+)](cyt) concentration, in terms of amplitude, frequency and duration, is
      likely very important for decoding the specific downstream responses for salinity
      stress tolerance in planta. It has been observed that the signatures of
      [Ca(2+)](cyt) and pH differ in various studies reported so far depending on the
      techniques used to measure them, and also depending on the plant organs where
      they are measured, such as root, shoot tissues or cells. This review describes
      the recent advances about the changes in [Ca(2+)](cyt) and pH(cyt) at both
      cellular and whole-plant levels under salinity stress condition, and in various
      salinity-tolerant and -sensitive plant species.

PMID- 20037470
TI  - Root growth is affected differently by mechanical wounding in seedlings of the
      ecological model species Nicotiana attenuata and the molecular model species
      Arabidopsis thaliana.
AB  - In the ecological model plant Nicotiana attenuata, leaf wounding or herbivory
      lead to a reduction of root growth via jasmonic acid (JA) signaling. A single
      wounding treatment is sufficient to induce this response; multiple wounding does
      not increase the plant growth reaction. In a recent study, in which JA bursts
      were elicited in leaves of the molecular model species Arabidopsis thaliana in
      different ways,(1) we tested whether JA induces the same response there. Root
      growth reduction was neither induced by foliar application of herbivore oral
      secretions nor by direct application of methyl jasmonate to leaves. Root growth
      reduction was observed when leaves were infected with the pathogen Pseudomonas
      syringae pv. tomato, which persistently induces the JA signaling pathway. Yet,
      growth analyses of this effect in wild type and JA-signaling mutants showed that
      it was elicited by the bacterial toxin coronatine which suggests ethylene-but not
      JA-induced root growth reduction in A. thaliana. Moreover, the growth effects
      were somewhat masked by a light-induced diurnal decrease of root growth. Overall,
      we conclude that the reaction of root growth to herbivore-induced JA signaling
      differs among species, which is related to different ecological defence
      strategies that have evolved in different species.

PMID- 20037472
TI  - Overexpression of the CBF2 transcriptional activator in Arabidopsis counteracts
      hormone activation of leaf senescence.
AB  - CBF1-3 (C-repeat binding factors) are transcriptional activators governing plant
      responses to low temperatures. Overexpression of CBF1-3 genes enhances plant
      frost tolerance, but also causes various pleiotropic effects regarding plant
      growth and development, mainly growth retardation, and delay of flowering and
      senescence. In a recent study, we reported that overexpression of CBF2 suppressed
      leaf senescence induced by the stress hormone ethylene. Here we show that
      overexpression of CBF2 also suppressed chlorophyll breakdown and leaf senescence
      induced by the phytohormones abscisic acid (ABA), salicylic acid (SA) and methyl
      jasmonate (MeJA), which indicates its broader role in suppressing hormone-induced
      leaf senescence. As previously reported for ethylene, the observed decrease in
      responsiveness to ABA in CBF2-overexpressing plants was specific to leaf
      senescence, since other responses to ABA were similar to those of wild-type
      plants. Transcript profiling analysis of hormone metabolism and responsive genes
      revealed that overexpression of CBF2 induced expression of ABA-biosynthesis and
      ABA-responsive genes and suppressed SA- and JA-related genes. Overall, in light
      of the adverse effects of CBF2 on ABA metabolism and responsiveness, on the one
      hand, and SA and JA metabolism and responsiveness, on the other hand, we conclude
      that overexpression of CBF2 suppresses hormone-induced leaf senescence by
      directly counteracting the hormone effects on leaf senescence and not by general
      suppression of their synthesis or signal transduction pathways.

PMID- 20037473
TI  - New insights into the early biochemical activation of jasmonic acid biosynthesis
      in leaves.
AB  - In plants, herbivore attack elicits the rapid accumulation of jasmonic acid (JA)
      which results from the activation of constitutively expressed biosynthetic
      enzymes. The molecular mechanisms controlling the activation of JA biosynthesis
      remain largely unknown however new research has elucidated some of the early
      regulatory components involved in this process. Nicotiana attenuata plants, a
      wild tobacco species, responds to fatty acid amino acid conjuguates (FAC)
      elicitors in the oral secretion of its natural herbivore, Manduca sexta, by
      triggering specific defense and tolerance responses against it; all of the
      defense responses known to date require the amplification of the wound-induced JA
      increase. We recently demonstrated that this FAC-elicited JA burst requires an
      increased flux of free linolenic acid (18:3) likely originating from the
      activation of a plastidial glycerolipase (GLA1) which is activated by an abundant
      FAC found in insect oral secretions, N-linolenoyl-glutamate (18:3-Glu). The lack
      of accumulation of free 18:3 after elicitation suggests a tight physical
      association between GLA1 and LOX3 in N. attenuata leaves. In addition, the
      salicylate-induced protein kinase (SIPK) and the nonexpressor of PR-1 (NPR1)
      participate in this activation mechanism that controls the supply of 18:3. In
      contrast, the wound-induced protein kinase (WIPK) does not but instead regulates
      the conversion of 13(S)-hydroperoxy-18:3 into 12-oxo-phytodienoic acid (OPDA).
      These results open new perspectives on the complex network of signals and
      regulatory components inducing the JA biosynthetic pathway.

PMID- 20037474
TI  - APC-targeted RAA1 degradation mediates the cell cycle and root development in
      plants.
AB  - Protein degradation by the ubiquitin-proteasome system is necessary for a normal
      cell cycle. As compared with knowledge of the mechanism in animals and yeast,
      that in plants is less known. Here we summarize research into the regulatory
      mechanism of protein degradation in the cell cycle in plants. Anaphase-promoting
      complex/cyclosome (APC), in the E3 family of enzymes, plays an important role in
      maintaining normal mitosis. APC activation and substrate specificity is
      determined by its activators, which can recognize the destruction box (D-box) in
      APC target proteins. Oryza sativa root architecture-associated 1 (OsRAA1) with
      GTP-binding activity was originally cloned from rice. Overexpression of of OsRAA1
      inhibits the growth of primary roots in rice. Knockdown lines showed reduced
      height of seedlings because of abnormal cell division. OsRAA1 transgenic rice and
      fission yeast show a higher proportion of metaphase cells than that of controls,
      which suggests a blocked transition from metaphase to anaphase during mitosis.
      OsRAA1 co-localizes with spindle tubulin. It contains the D-box motif and
      interacts with OsRPT4 of the regulatory particle of 26S proteasome. OsRAA1 may be
      a cell cycle inhibitor that can be degraded by the ubiquitin-proteasome system,
      and its disruption is necessary for the transition from metaphase to anaphase
      during root growth in rice.

PMID- 20037475
TI  - The cephalic neural crest of amniote vertebrates is composed of a large majority
      of precursors endowed with neural, melanocytic, chondrogenic and osteogenic
      potentialities.
AB  - In the amniote embryo, the neural crest (NC) has the unique capacity to give rise
      to neuronal and glial cells in the peripheral nervous system (PNS), melanocytes
      and mesenchymal cells including those forming the head skeleton and connective
      tissues. In the trunk, mesenchymal cells are derived from the mesoderm. The
      question was raised whether the NC-derived head mesenchyme arises from a lineage
      separate from the neural-melanocytic one, or if both skeletogenic and neural
      melanocytic derivatives originate from a common putative stem cell in the early
      cephalic NC. We discuss here these issues and present experimental data that
      provide evidence for the multipotency of NC cells (NCC), focusing on those at the
      origin of the craniofacial skeleton. Recent work of in vitro clonal culture
      revealed that the vast majority (92% of clonogenic cells) of the cephalic quail
      NCC are capable to yield osteoblasts together with neurones, glial cells and
      melanocytes. A common pluripotent progenitor for chondrocytes, osteocytes,
      neurones, glial cells, melanocytes and myofibroblasts has been identified and is
      present in the early cephalic NC at the frequency of 7 to 13% of clonogenic cells
      depending on the environmental conditions. Together with recent reports that
      multipotent NC-related progenitors persist in adult tissues in rodents and
      humans, these results reinforce a stem cell model for the generation and
      maintenance of NC-derived lineages during embryogenesis and in adult tissue
      homeostasis.

PMID- 20037476
TI  - Small and remarkable: The Micro-Tom model system as a tool to discover novel
      hormonal functions and interactions.
AB  - Hormones are molecules involved in virtually every step of plant development and
      studies in this field have been shaping plant physiology for more than a century.
      The model plant Arabidopsis thaliana, long used as a tool to study plant
      hormones, lacks significant important developmental traits, such as fleshy
      climacteric fruit, compound leaf and multicellular trichomes, suggesting the
      necessity for alternative plant models. An attractive option often used is
      tomato, a species also of major economic importance, being ideal to bring
      together basic and applied plant sciences. The tomato Micro-Tom (MT) cultivar
      makes it possible to combine the direct benefits of studying a crop species with
      the fast life cycle and small size required for a suitable biological model.
      However, few obscure questions are constantly addressed to MT, creating a process
      herein called "MT mystification". In this work we present evidence clarifying
      these questions and show the potential of MT, aiming to demystify it. To
      corroborate our ideas we showed that, by making use of MT, our laboratory
      demonstrated straightforwardly new hormonal functions and also characterized a
      novel antagonistic hormonal interaction between jasmonates and brassinosteroids
      in the formation of anti-herbivory traits in tomato.

PMID- 20037477
TI  - ERECTA controls low light intensity-induced differential petiole growth
      independent of phytochrome B and cryptochrome 2 action in Arabidopsis thaliana.
AB  - Plants can respond quickly and profoundly to changes in their environment.
      Several species, including Arabidopsis thaliana, are capable of differential
      petiole growth driven upward leaf movement (hyponastic growth) to escape from
      detrimental environmental conditions. Recently, we demonstrated that the leucine
      rich repeat receptor-like Ser/Thr kinase gene ERECTA, explains a major effect
      Quantitative Trait Locus (QTL) for ethylene-induced hyponastic growth in
      Arabidopsis. Here, we demonstrate that ERECTA controls the hyponastic growth
      response to low light intensity treatment in a genetic background dependent
      manner. Moreover, we show that ERECTA affects low light-induced hyponastic growth
      independent of Phytochrome B and Cryptochrome 2 signaling, despite that these
      photoreceptors are positive regulators of low light-induced hyponastic growth.

PMID- 20037479
TI  - Effects of blue-green algae extracts on the proliferation of human adult stem
      cells in vitro: a preliminary study.
AB  - BACKGROUND: Adult stem cells are known to have a reduced restorative capacity as
      we age and are more vulnerable to oxidative stress resulting in a reduced ability
      of the body to heal itself. We have previously reported that a proprietary
      nutraceutical formulation, NT-020, promotes proliferation of human hematopoietic
      stem cells in vitro and protects stem cells from oxidative stress when given
      chronically to mice in vivo. Because previous reports suggest that the blue green
      algae, Aphanizomenon flos-aquae (AFA) can modulate immune function in animals, we
      sought to investigate the effects of AFA on human stem cells in cultures.
      MATERIAL/METHODS: Two AFA products were used for extraction: AFA whole (AFA-W)
      and AFA cellular concentrate (AFA-C). Water and ethanol extractions were
      performed to isolate active compounds for cell culture experiments. For cell
      proliferation analysis, human bone marrow cells or human CD34+ cells were
      cultured in 96 well plates and treated for 72 hours with various extracts. An MTT
      assay was used to estimate cell proliferation. RESULTS: We report here that the
      addition of an ethanol extract of AFA-cellular concentrate further enhances the
      stem cell proliferative action of NT-020 when incubated with human adult bone
      marrow cells or human CD34+ hematopoietic progenitors in culture. Algae extracts
      alone had only moderate activity in these stem cell proliferation assays.
      CONCLUSIONS: This preliminary study suggests that NT-020 plus the ethanol extract
      of AFA cellular concentrate may act to promote proliferation of human stem cell
      populations.

PMID- 20037478
TI  - A resource for analysis of microRNA expression and  function in pancreatic ductal
      adenocarcinoma cells.
AB  - MicroRNAs (miRNAs) are 21-24 nucleotide RNA molecules that regulate the
      translation and stability of target messenger RNAs. Abnormal miRNA expression is
      a common feature of diverse cancers. Several previous studies have classified
      miRNA expression in pancreatic ductal adenocarcinoma (PDAC), although no uniform
      pattern of miRNA dysregulation has emerged. To clarify these previous findings as
      well as to set the stage for detailed functional analyses, we performed global
      miRNA expression profiling of 21 human PDAC cell lines, the most extensive panel
      studied to date. Overall, 39 miRNAs were found to be dysregulated and have at
      least two-fold or greater differential expression in PDAC cell lines compared to
      control nontransformed pancreatic ductal cell lines. Several of these miRNAs show
      comparable dysregulation in first-passage patient derived xenografts. Initial
      functional analyses demonstrate that enforced expression of miRNAs derived from
      the miR-200 family and the miR-17-92 cluster, both of which are overexpressed in
      PDAC cell lines, enhances proliferation. In contrast, inhibition of the miR-200
      family, the miR-17-92 cluster, or miR-191 diminishes anchorage independent
      growth. Consistent with a known role for the miR-200 family in negatively
      regulating an epithelial-to-mesenchymal transition (EMT), the abundance of these
      miRNAs correlated positively with E-cadherin expression and negatively with the
      EMT-associated transcription factor and established miR-200 target ZEB1. Finally,
      restituted expression of miR-34a, a miRNA whose expression is frequently lost in
      PDAC cell lines, abrogates growth, demonstrating that the anti-proliferative
      activity of this miRNA is operative in PDAC. These results, and the widespread
      availability of PDAC cell lines wherein the aforementioned data were generated,
      provide a valuable resource for the pancreatic cancer research community and will
      greatly facilitate functional studies essential for elucidating the consequences
      of miRNA dysregulation in pancreatic cancer.

PMID- 20037480
TI  - Effect of carbogen on tumour oxygenation and 32P-colloid interstitial irradiation
      response.
AB  - BACKGROUND: Interstitial irradiation therapy using radionuclides is a slow and
      continual process in which the effect is exerted gradually, thus improvement of
      the hypoxic status of the tumor will also take a long time. It has been known
      that carbogen delivery of 5-15 min increases tumor oxygenation. However, the long
      term effect of carbogen breathing on hypoxic cells has not yet been determined,
      and little is know about the effect of carbogen breathing for sensitization to
      interstitial irradiation therapy. MATERIAL/METHODS: 99mTc-HL91(99mTc 4,9-diaza
      3,3,10,10-tetramethyldodecan-2,1-dione dioxime) hypoxic imaging was performed in
      10 mice bearing sarcoma 180 (S180) before and after 2 h carbogen breathing.
      Radioactivity ratios of tumor to contralateral limbs (T/L) of the 2 images were
      calculated and compared. Mice bearing S180 were subjected to long-term carbogen
      breathing (2 h/day for 24 days), and were treated with or without 32P-colloid.
      Tumor growth rate was observed in the S180-bearing mice. RESULTS: T/L of 99mTc
      HL91 uptake before and after carbogen breathing was 1.872+/-0.391 and 1.354+/
      0.189, respectively (t=4.476, P<0.01). In mice in the 32P-treated air breathing
      group and 32P-treated carbogen breathing group, tumor growth rate did not differ
      on day 12 after 32P-colloid treatment, and on day 24 the tumor volume was 2.728+/
      0.469 and 2.237+/-0.603 cm3 (t=2.128, P<0.05), respectively, with tumor mass
      being 2.437+/-0.447 and 1.965+/-0.538 g (t=2.134, P<0.05), respectively.
      CONCLUSIONS: Long-term carbogen breathing can increase tumor oxygenation and
      continual carbogen breathing is necessary for enhancing the therapeutic effect of
      32P-colloid interstitial irradiation.

PMID- 20037481
TI  - Complement 5b-9 complex-induced alterations in human RPE cell physiology.
AB  - BACKGROUND: Recent evidence shows that complements are closely related to the
      occurrence of choroidal neovascularization (CNV). We studied the effect of
      complement 5b-9 complex (C5b-9) on membrane permeability and molecular biological
      behavior in cultured human retinal pigment epithelium (RPE) cells and considered
      the role of C5b-9 in CNV. MATERIAL/METHODS: Human RPE cells were exposed to
      different concentrations of C5b-9 for 24 hours, then observed through light and
      electron microscopy. The dynamics of calcium ion change in cells exposed to
      sublysis C5b-9 were analyzed by confocal laser scanning microscope, and the
      amount of VEGF and TGF-beta2 mRNA was determined by reverse transcription
      polymerase chain reaction (RT-PCR) RESULTS: RPE cells were destroyed when exposed
      to 80 microg/ml and 40 microg/ml C5b-9. The structure of RPE cells was not
      obviously changed when exposed to 20 microg/ml or less C5b-9; however, pigment
      granules are released from the cell membrane when observed using electron
      microscopy. In most of the cells, calcium fluorescence intensity increased
      rapidly after the deposition of C5b-9, to a peak at 4 min, lasted for about 6
      min, and then began to decrease. The expression of VEGF and TGF- beta2 mRNA in
      RPE cells with C5b-9 was increased at 4 h and decreased at 24 h, but they were
      higher than in the control group. CONCLUSIONS: These observations suggest C5b-9
      can induce a change in membrane permeability, an increase in cytoplasmic calcium
      ion concentration, and significant up-regulation of angiogenic factors in
      cultured RPE cells, which may be one of many potential mechanisms of CNV
      formation.

PMID- 20037482
TI  - Histological comparison of autograft, allograft-DBM, xenograft, and synthetic
      grafts in a trabecular bone defect: an experimental study in rabbits.
AB  - BACKGROUND: Different types of bone-graft substitutes have been developed and are
      on the market worldwide to eliminate the drawbacks of autogenous grafting. This
      experimental animal study was undertaken to evaluate the different histological
      properties of various bone graft substitutes utilized in this hospital.
      MATERIAL/METHODS: Ninety New Zealand white rabbits were divided into six groups
      of 15 animals. Under general anesthesia, a 4.5 mm-wide hole was drilled into both
      the lateral femoral condyles of each rabbit, for a total of 180 condyles for
      analysis. The bone defects were filled with various grafts, these being 1)
      autograft, 2) DBM crunch allograft (Grafton), 3) bovine cancellous bone xenograft
      (Lubboc), 4) calcium phosphate hydroxyapatite substitute (Ceraform), 5) calcium
      sulfate substitute (Osteoset), and 6) no filling (control). The animals were
      sacrificed at 1, 3, and 6 months after implantation and tissue samples from the
      implanted areas were processed for histological evaluation. A histological
      grading scale was designed to determine the different histological parameters of
      bone healing. RESULTS: The highest histological grades were achieved with the use
      of cancellous bone autograft. Bovine xenograft (Lubboc) was the second best in
      the histological scale grading. The other substitutes (Grafton, Ceraform,
      Osteoset) had similar scores but were inferior to both allograft and xenograft.
      CONCLUSIONS: Bovine xenograft showed better biological response than the other
      bone graft substitutes; however, more clinical studies are necessary to determine
      its overall effectiveness.

PMID- 20037483
TI  - Expression of genes related to oxidative/nitrosative stress in mouse hearts:
      effect of preconditioning and cholesterol diet.
AB  - BACKGROUND: The aim of our study was to explore the effect of high-cholesterol
      diet and preconditioning on cardiac gene expression patterns in mouse hearts,
      focusing on genes involved in nitric oxide (NO) and free radical signaling and
      the mevalonate pathway. MATERIAL/METHODS: Mice were fed 2% high-cholesterol or
      normal diet for 8 weeks. Hearts isolated from both groups were subjected to
      either a preconditioning (PC) protocol (3 cycles of 5 min ischemia and 5 min
      aerobic perfusion) or a time-matched non-preconditioning protocol followed by 30
      min global test ischemia and 2 hour reperfusion. RESULTS: PC altered gene
      expression only in the mice subjected to a normal diet, as shown in neuronal
      nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS) and the
      superoxide-producing enzymes xanthine oxidase (XO) and nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidases 1 and 4. The rate-limiting enzyme of the
      mevalonate pathway, 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      showed differential expression in the myocardium in response to I/R and PC in
      mice on normal diet but not in cholesterol-fed animals. CONCLUSIONS: We conclude
      that cholesterol-enriched diet leads to alterations in preconditioning-induced
      gene expression in the mouse heart, which might lead to marked changes of
      oxidative/nitrosative stress signaling and to the attenuation of the
      cardioprotective effect of preconditioning.

PMID- 20037484
TI  - Comparison of thin-strut cobalt-chromium stents and stainless steel stents in a
      porcine model of neointimal hyperplasia.
AB  - BACKGROUND: The high radial force and durability of cobalt-chromium alloy enable
      the construction of low-profile stents with thin struts, which improves their
      elasticity and may play a key role in reducing the incidence of neointimal
      hyperplasia as well as allow faster endothelialization. The aim of this study was
      to compare cobalt-chromium (CoCr) and stainless steel (SS) coronary stents in a
      pig model of neointimal hyperplasia. MATERIAL/METHODS: Eighteen stents were
      implanted into the coronary arteries of nine pigs. Control coronarography was
      performed 28 days after stent implantation. The animals were then sacrificed,
      their hearts explanted, and the coronary arteries isolated for further
      histopathological analysis. RESULTS: Quantitative coronary angiography and
      histomorphometric analysis revealed no statistically significant difference
      between the two groups of stents. However, there was a trend toward greater late
      lumen loss (p=0.09) and neointimal area in the CoCr stents (p=0.08). The
      qualitative histopathology of the CoCr stents revealed findings typical of bare
      metal stents reviewed in the literature and approved for use in clinical
      practice. No signs of stent thrombosis, necrosis, or fibrin deposits were
      observed nor signs of excessive inflammatory reaction. Endothelialization was
      complete within 28 days. CONCLUSIONS: Despite thinner struts, CoCr stents have no
      advantage over stainless steel stents in terms of neointimal hyperplasia
      inhibition. However, their positive safety results together with their high
      radial strength, low profile, and excellent elasticity can ensure their usage,
      especially in lesions of complex morphology.

PMID- 20037485
TI  - Synergistic action of doxorubicin and sulindac in human cervix carcinoma cells -
      studies on possible mechanisms.
AB  - BACKGROUND: Epidemiologic and experimental studies have shown that cyclooxygenase
      2 (COX-2) inhibitors as non-steroidal anti-inflammatory drugs (NSAIDs) are
      effective chemopreventive agents. The mechanisms underlying the antitumor
      activity of COX-2 inhibitors are thought to involve inhibition of COX-2 enzyme
      activity and induction of apoptosis. The aim of the current work was to study the
      mechanisms of synergistic action noted in HeLa cervical carcinoma cells under
      doxorubicin (DOX) and sulindac (SUL) co-treatment. MATERIAL/METHODS: Cytotoxic
      activity of the drugs was defined with MTT test, apoptosis was detected with
      TUNEL test, DOX transmembrane efflux was measured fluorometrically, expression of
      MDR-1 and MRP-1 was determined with quantitative real time - PCR (QRT-PCR).
      RESULTS: It was shown that SUL at non-toxic concentrations, 10 and 50 microM, is
      an effective enhancer of cytotoxic action for DOX in 0.5 and 1 microM,
      respectively; however, only for SUL concentration equal to 50 microM potentiated
      apoptosis induced by 1 microM of DOX. Moreover, blocking DOX efflux outside the
      cells was observed. The QRT - PCR analysis has shown that, when used
      simultaneously, DOX 1 microM and SUL 50 microM results in decreased mRNA level
      for MDR-1 and MRP-1. CONCLUSIONS: It is concluded that cytotoxic action of DOX
      against HeLa cells is enhanced by non-toxic concentrations of SUL. The observed
      effect is due to quenching of MDR-1 and MRP-1 genes expression, which results in
      blocking of efflux of DOX outside the cells, which in turn correlates with
      enhanced apoptotic effects. According to obtained results the mechanisms of
      potentiating of DOX action by SUL are dose specific.

PMID- 20037486
TI  - Barrier functionality and transport machineries of human ECV304 cells.
AB  - BACKGROUND: The lack of a brain-derived endothelial cell-based model has led
      researchers to exploit non-brain endothelial/epithelial cells as in vitro models
      for blood-brain barrier (BBB) investigations. Of these, the endothelial-like
      human ECV304 cell line was initially characterized as endothelial cells and has
      been widely used as an in vitro BBB model. It was later shown to be T24 bladder
      carcinoma epithelial cells. To pursue its potential as a cell-based model for
      drug screening and transport machineries, ECV304 cells were evaluated for their
      barrier and plasma membrane characteristics. MATERIAL/METHODS: ECV304 cells
      treated with some tight-junction modulators (e.g. cAMP elevators, butyric acid,
      dexamethasone, gamma-linolenic acid, and astrocytic factors) were examined for
      bioelectrical resistance, transcellular/paracellular permeability, and
      functionality expression of some key transporters. RESULTS: A significant
      (p<0.05) increase in trans-endothelial electrical resistance (TEER) was observed
      in ECV304 cells treated with astrocytic factors and cAMP elevators (i.e. to
      approximately 110Omega*cm2 vs. approximately 60 Omega*cm2 in the control). Such
      treatment also yielded high discrimination in the permeability coefficients of
      the transcellular marker propranolol (25x10-6 cm/sec) and the paracellular marker
      sucrose (11.3 x 10-6 cm/sec). Carrier-mediated transporters such as GLUT-1,
      system L, and P-glycoprotein (P-gp) as well as endocytic transport machineries
      (e.g. clathrin and caveolin) were found to be functionally expressed.
      CONCLUSIONS: ECV304 cells failed to generate a discriminative tight barrier even
      in the presence of tight-junction modulators. Thus their implementation in drug
      permeability screening is not recommended. They display some important key
      carrier-mediated transport systems and can be considered as a useful cell-based
      in vitro model.

PMID- 20037487
TI  - Protective effects of carvedilol on systemic vascular damage induced by
      angiotensin II: organ-specific effects independent of antihypertensive effects.
AB  - BACKGROUND: The protective effect of carvedilol on multiple organ damage induced
      by angiotensin II (Ang II) remains unclear. The aim of this study was to evaluate
      the protective effect of carvedilol on the heart, liver, and kidney in rats
      infused with Ang II. MATERIAL/METHODS: Wistar rats were randomly distributed into
      three groups: control (no treatment), continuously infused with Ang II (150
      etag/min for 72 hr), and treated with Ang II + carvedilol (90 mg/kg/d).
      Histological sections of the myocardium, kidney, and liver were analyzed for the
      presence of necrosis. RESULTS: Ang II induced arterial hypertension which was not
      affected by carvedilol treatment (tail-cuff blood pressures, control: 125+/-13.6,
      Ang II: 163+/-27.3, Ang II + CV: 178+/-39.8 mmHg, p<0.05). Also, there were
      perivascular inflammation and necrosis in the myocardium, kidney, and hepatocytes
      necrosis around the terminal vein. Carvedilol treatment fully prevented damage to
      the heart and kidney and attenuated liver lesions induced by the Ang II infusion.
      CONCLUSIONS: The protective effect of carvedilol on perivascular damage induced
      by Ang II infusion depended on the target organ. The prevention of heart damage
      occurred independently of the antihypertensive effects of carvedilol.

PMID- 20037488
TI  - Smoking and other personal characteristics as potential predictors for fecal
      bacteria populations in humans.
AB  - BACKGROUND: Intestinal microbes have been postulated to play an important role in
      the development of colorectal cancer. Recently developed methods for preserving
      and delivering fecal samples at ambient temperature to the laboratory for
      molecular analysis of bacterial constituents were used to test associations of
      bacterial populations with epidemiologic risk factors for colorectal cancer.
      MATERIAL/METHODS: Real-time PCR targeting 16S rRNA gene sequences was used to
      quantify three intestinal bacterial groups relative to total DNA in stool samples
      preserved with RNAlater from 62 subjects. Subjects' medical and family history,
      race, diet, weight, height, and personal habits including smoking were obtained
      through structured questionnaires. RESULTS: Bacteroides DNA proportions were
      relatively stable among individuals and relatively independent of dietary intake
      or other personal factors. Clostridium (coccoides group) DNA was positively
      associated with total fat and vitamin C intake. Desulfovibrio DNA amount tended
      to be higher in African Americans than in other races. Furthermore, Desulfovibrio
      DNA increased progressively with pack-years of cigarette smoking. The relative
      DNA quantity (%) was more than 17 times higher in the subjects who smoked at
      least 15 pack-years compared with never-smokers (P-value for a linear trend
      =0.001). In addition, Desulfovibrio DNA (%) decreased with increased calcium,
      vitamin E, and dietary fiber intake. However, only smoking remained significant
      in multivariable analysis. CONCLUSIONS: Although the study was limited by its
      sample size, these results suggest that smoking (or possibly unmeasured dietary
      confounders) may exert modulatory effects on the bacterial populations of the
      gastrointestinal tract. The study also demonstrates collection, preservation, and
      sample delivery procedures suitable for large epidemiological studies.

PMID- 20037489
TI  - Characteristics and prognosis of coronary revascularization procedure in patients
      age 80 and older presenting with acute myocardial infarction.
AB  - BACKGROUND: Elderly patients are underrepresented in randomized trials evaluating
      strategies of early coronary revascularization in acute myocardial infarction
      (MI), whereas in real life octogenarians represent the fastest-growing segment of
      our population. We sought to describe the characteristics and outcome of patients
      > or = 80 years referred to a catheterization laboratory for MI.
      MATERIAL/METHODS: We studied 1687 consecutive patients referred to our cath
      laboratory for MI, divided into 2 groups: group 1 patients aged > or =80 years
      (n=152) and group 2 (<80 years, [n=1535]). Baseline clinical and angiographic
      characteristics and mortality were studied. RESULTS: Cardiogenic shock and three
      vessel disease were more frequent in the patients > or =80 years (p<0.0001).
      Angiographic success of percutaneous coronary interventions was high in elderly
      patients (89.5%), but was significantly lower as compared to group 2 (p<0.0001).
      In-hospital mortality was 18% in group 1 versus 5.5% in group 2 (p<0.0001). No
      patient from group 1 presenting anterior MI with cardiogenic shock survived. The
      rate of mortality in group 1 between the end of hospitalization and one year
      following MI was only 4% (versus 3% in group 2, p=0.58). Long-term prognosis of
      elderly patients was similar as compared to expected survival of subjects > or
      =80 years. CONCLUSIONS: This study demonstrates that the angiographic
      characteristics of patients > or =80 years are significantly different,
      associated with an initial increased risk of mortality, and that prognosis of MI
      is excellent once the acute phase has passed.

PMID- 20037490
TI  - Threshold estimation in adult normal- and impaired-hearing subjects using
      auditory steady-state responses.
AB  - BACKGROUND: The aim of the study was to compare the estimation of hearing
      threshold values by behavioral and electrophysiological (ASSR) methods in
      subjects with normal hearing and those with sensorineural hearing impairment.
      MATERIAL/METHODS: Thirty-two subjects (17 male and 15 female) were tested, with a
      total of 61 ears. Of these, 11 (22 ears) presented normal hearing threshold
      values (0-19 dBHL) and 21 (39 ears) sensorineural deficits. RESULTS: The data
      showed that for the normal-hearing subjects the mean +/-SD ASSR threshold was
      approximately 20+/-11 dB for frequencies of 0.25-1.0 kHz. For higher frequencies
      the ASSR threshold increased to 40+/-12.5 dB at 8.0 kHz. Regression analysis
      confirmed that the difference between the ASSR-estimated and behavioral threshold
      values decreased significantly with the amount of hearing loss. The data showed
      that for a 10-dB increment of the behavioral threshold, the ASSR threshold
      increased by 7 dB. The difference of about 27 dB between the two methods observed
      in normal subjects tends to cancel in hearing loss greater than 95-100 dBHL.
      CONCLUSIONS: The results of these analyses indicate that the threshold estimates
      are rather discordant with the behavioral thresholds. in particular it seems that
      the correction factor applied here does not rely on factors adequately modeled
      (in terms of instrumentation) to compensate for the effects of hearing loss on
      ASSR thresholds. The threshold estimation is adequately modeled for high levels
      of hearing loss, particularly for patients requiring a cochlear implant.

PMID- 20037491
TI  - Aronia melanocarpa extract reduces blood pressure, serum endothelin, lipid, and
      oxidative stress marker levels in patients with metabolic syndrome.
AB  - BACKGROUND: Experimental studies have shown that anthocyanins may exert
      pleiotropic effects. The aim of the study was to determine the influence of
      Aronia melanocarpa extract on blood pressure and serum concentration of
      endothelin-1 (ET-1), lipids, glucose, uric acid, C-reactive protein (CRP),
      fibrinogen, the antioxidant enzymes catalase (CAT), superoxide dysmutase (SOD),
      and glutathione peroxidase (GSH-Px), and lipid peroxidation (thiobarbituric acid
      reacting substrates, TBARS) in erythrocytes of patients with metabolic syndrome
      (MS). MATERIAL/METHODS: The study comprised 22 healthy volunteers and 25 patients
      with MS. Patients with MS were treated with aronia extract (3 x 100 mg/day) for
      two months. The above parameters were measured. RESULTS: After two months of
      therapy, statistically significant decreases were observed in SBP (143.40+/-7.87
      vs. 131.83+/-12.24 mmHg, p<0.001), DBP (87.20+/-9.9 vs. 82.13+/-10.33 mmHg,
      p<0.05), ET-1 (2.44+/-0.51 vs. 1.74+/-0.42 pg/ml, p<0.001), TC (242.80+/-34.48
      vs. 227.96+/-33.07 mg/dl, p<0.001), LDL-C (158.71+/-35.78 vs. 146.21+/-34.63
      mg/dl, p<0.01), TG (215.92+/-63.61 vs. 187.58+/-90 mg/dl, p<0.05), TBARS
      (0.0712+/-0.0191 vs. 0.0362+/-0.0135 micromol/g-Hb, p<0.001), and CAT (261.30+/
      59.78 vs. 213.34+/-47.36 U/mg-Hb) and significant increases in SOD (2380.63+/
      419.91 vs. 3066.53+/-542.24 U/g-Hb, p<0.001), GSH-Px (12.60+/-5.97 vs. 19.18+/
      9.09 U/g-Hb, p<0.01), and fibrinogen levels (249.20+/-27.17 vs. 276.67+/-57.41
      mg/dl, p<0.05) compared with the baseline values. CONCLUSIONS: Aronia extract may
      be of benefit to patients with MS. This seems to result from the influence of
      anthocyanins and possibly other flavonoids on blood pressure, serum level of ET
      1, lipids, and oxidative status (GSH-Px, SOD, TBARS).

PMID- 20037492
TI  - Short term health impact of a yoga and diet change program on obesity.
AB  - BACKGROUND: Obese persons often find physical activity difficult. The effects of
      a yoga and diet change program, emphasizing breathing techniques practiced while
      seated, was assessed in obese persons. MATERIAL/METHODS: A single group of 47
      persons were assessed on the first and last day of a yoga and diet change
      program, with 6 days of the intervention between assessments. The assessments
      were: body mass index (BMI), waist and hip circumferences, mid-arm circumference,
      body composition, hand grip strength, postural stability, serum lipid profile and
      fasting serum leptin levels. Participants practiced yoga for 5 hours every day
      and had a low fat, high fiber, vegetarian diet. Last and first day data were
      compared using a t-test for paired data. RESULTS: Following the 6-day residential
      program, participants showed a decrease in BMI (1.6 percent), waist and hip
      circumferences, fat-free mass, total cholesterol (7.7 percent decrease), high
      density lipoprotein (HDL) cholesterol (8.7 percent decrease), fasting serum
      leptin levels (44.2 percent decrease) and an increase in postural stability and
      hand grip strength (p<0.05, all comparisons). CONCLUSIONS: A 6-day yoga and diet
      change program decreased the BMI and the fat-free mass. Total cholesterol also
      decreased due to reduced HDL levels. This suggests that a brief, intensive yoga
      program with a change in diet can pose certain risks. Benefits seen were better
      postural stability, grip strength (though a 'practice effect' was not ruled out),
      reduced waist and hip circumferences and a decrease in serum leptin levels.

PMID- 20037493
TI  - Effect of levothyroxine replacement therapy on paraoxonase-1 and carotid intima
      media thickness in subclinical hypothyroidism.
AB  - BACKGROUND: Paraoxonase-1 (PON-1) may play an important role in atherosclerosis.
      Atherosclerosis is an inflammatory disease and C-reactive protein is a marker for
      inflammation. The aim of this study was to determine serum PON-1 activity and
      high-sensitivity C-reactive protein (hs-CRP) levels and assess carotid intima
      media thickness, a marker of early atherosclerotic changes, in patients with
      subclinical hypothyroidism. MATERIAL/METHODS: hs-CRP concentrations and PON-1
      activity with respect to carotid intima-media thickness were evaluated in 38
      subclinical hypothyroidism patients (normolipidemic, mean age: 49.79+/-10.04
      years) before and after 3 months of stable euthyroidism and compared with those
      of 19 euthyroid normolipidemic healthy individuals (mean age: 49.95+/-8.12
      years). RESULTS: At baseline, the patients with subclinical hypothyroidism had
      similar levels of PON-1 activity and hs-CRP and a similar lipid profile as the
      controls; however, the carotid intima-media thickness was greater than in the
      controls. Levothyroxine treatment had no effect on serum PON-1 activity and hs
      CRP level, but it resulted in a significant reduction in carotid intima-media
      thickness in the subclinical hypothyroidism patients. CONCLUSIONS: PON-1 activity
      and hs-CRP levels did not significantly differ between subclinical hypothyroid
      patients and controls. Although levothyroxine treatment might have the potential
      to reverse the progression of atherosclerosis in subclinical hypothyroid
      patients, PON-1 activity and hs-CRP levels were not affected by this treatment.
      The reduction in carotid intima-media thickness was independent of the decrease
      in serum lipid profile or other variables.

PMID- 20037495
TI  - Coagulation changes in a siamese twin in SIRS after death of the other twin: a
      case study.
AB  - BACKGROUND: Conjoined twins represent a rare case of embryonic failure. Siamese
      twins' final outcome is usually associated with poor prognosis due to
      complications, among which the inflammatory and septic disturbances are often
      present. CASE REPORT: The article describes Siamese twins of craniopagus type.
      One of the twins died of heart and aortic failure after 48 hours of life. The
      decision regarding surgical separation then became an emergency. At the same time
      laboratory results for the surviving twin I indicated steadily worsening
      coagulation functions and processes, which we believed were caused by the death
      of twin II, as well as by systemic inflammatory response syndrome (SIRS).
      CONCLUSIONS: Due to vascular conjunction between the twins' brains' circulatory
      systems the sequenced progress of coagulopathy was noticed in the surviving twin.

PMID- 20037494
TI  - Effects of mild-stream bathing on recovery from mental fatigue.
AB  - BACKGROUND: Bathing in hot water is very common in Japan; people bathe in order
      to clean their bodies and to recover from physical and mental fatigue. However,
      there have been few reports examining the effects of bathing on recovery from
      mental fatigue. The purpose of this study was to examine the effects of mild
      stream bathing on recovery from mental fatigue. MATERIAL/METHODS: During mild
      stream bathing, a mild stream continuously passes from the sole to the calf,
      thigh, waist and back, thus providing a massage function. In a double-blinded,
      placebo-controlled, crossover experiment, 14 male healthy volunteers were
      randomized into normal bathing and mild-stream bathing experiments. After a
      fatigue-inducing mental task for 4 hours, subjects took a normal or mild-stream
      bath. RESULTS: Heart rate was higher, muscle stiffness in the waist was lower and
      plasma cortisol levels tended to be lower after mild-stream bathing when compared
      to normal bathing. In addition, after mild-stream bathing, mental task
      performance, as assessed by reaction times on an advanced trail making test, was
      better than that after normal bathing. CONCLUSIONS: The present results suggest
      that improved working memory processing, diminished waist muscle tone, and
      attenuated mental stress are induced by mild-stream bathing. Therefore, mild
      stream bathing appears to be more effective for alleviating mental fatigue than
      normal bathing.

PMID- 20037496
TI  - Psychosexual biography and the strategies used by women afflicted with stress
      urinary incontinence during intercourse: two case studies.
AB  - BACKGROUND: Stress urinary incontinence often leads to major physical,
      psychological and social problems, and many patients struggle to cope with this
      illness. The issue of urinary leakage during sex is particularly troublesome.
      CASE REPORT: In order to show the relationship between psychosexual biography and
      the strategies applied to cope with urinary leakage during sexual intercourse, we
      analyzed the psychosexual biographies of 2 patients with stress urinary
      incontinence. CONCLUSIONS: Psychosexual biography influences the choice of
      strategies used by incontinent women to cope with urinary leakage during sexual
      intercourse. Normal psychosexual development in all developmental stages
      conditions proper sexual functioning in women with urinary leakage during sexual
      intercourse and the choice of less restrictive coping strategies.

PMID- 20037497
TI  - Statins and beta-cell function.
AB  - Statins, as 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors, have long been known for having significant effects on plasma lipid
      and lipoprotein profiles, lowering total and LDL cholesterol and raising HDL-C
      level. Many studies have previously found that statin therapy reduced the risk of
      occlusive vascular events in people with diabetes mellitus. In fact, type 2
      diabetes is often accompanied by abnormal blood lipid and lipoprotein levels, but
      most studies on the link between hyperlipidemia and pathogenesis of diabetes have
      focused on free fatty acids (FFAs), which were believed to enhance hyperglycemia-
      induced beta cell deterioration and insulin secretion impairment, while the
      impact of cholesterol in the pathogenesis of diabetes has not been reported.
      Although the relationship between elevated cholesterol and diabetes has not been
      extensively examined, there is some evidence supporting a potential link between
      the two. Firstly, lipoprotein level is closely correlated with the concentration
      of plasma cholesterol, and the former is a good predictor for onset of diabetes.
      Secondly, a few clinical studies have indicated that use of statins can delay the
      progression of diabetes. Though the mechanism underlying this phenomenon is still
      elusive, it was recently found that elevated serum cholesterol can impair insulin
      secretion and increase the rate of apoptosis in beta cells, which may offer a
      promising clue to how statins work.

PMID- 20037498
TI  - Cerebral atherosclerosis causes neurodegenerative diseases.

PMID- 20037499
TI  - Federal funding for needle exchange programs.
AB  - The HIV/AIDS pandemic has affected millions across the globe. The sharing of
      needles, for reasons of economy or social relations, has become the most common
      mode of HIV transmission among injection drug users. Needle exchange programs,
      which provide many services in addition to the exchange of clean needles for
      contaminated needles, have proven effective in reducing HIV rates among injection
      drug users in their communities. Although these programs have proven to be one of
      the most effective strategies in the efforts to reduce HIV rates, there has been
      a federal ban on the use of federal money for needle exchange programs since
      1989. This ban was introduced by Congress in accordance with the drug war
      ideology, a narrow and elusive plan to completely eradicate drug use in the
      United States. Although there are a significant number of government reports
      supporting needle exchange programs, including support from the CDC, American
      Medical Association, the National Institutes of Health, it appears as If public
      health and the lives of others have become a secondary concern to strong federal
      policy on eradicating drug use. Lifting the federal ban would save the country
      millions of lives and billions of dollars in healthcare costs. Needle exchange
      programs should be an integral part of HIV prevention strategy, and are ethically
      imperative as well, restoring human dignity to the clients that so often need
      it.<br />

PMID- 20037500
TI  - Social reintegration of TBI patients: a solution to provide long-term support.
AB  - BACKGROUND: This article evaluates the effectiveness of a workable long-term
      program to provide social support for TBI patients, based on the "Academy of
      Life" concept. Disability after TBI causes numerous disruptions of normal life,
      which affect the patient, the family, and society. The patient needs the
      particular kind of support the program was designed to provide. MATERIAL/METHODS:
      The study involved 200 married couples with a TBI spouse previously enrolled in
      the "Academy of Life." The methods included documentation analysis, clinical
      interviews, the Family Bonds Scale, the Social Isolation Scale, and the Social
      Functions subscale from a battery used to evaluate QOL after TBI. The subjects
      were examined before and after completing the program. RESULTS: In the first
      examination all types of family bonds were found to be severely weakened; there
      was deep social isolation, loneliness, sadness, a feeling of being surrounded by
      hostility, and no purposeful social activity. The most common form of support
      from significant others was pity and unwanted interference, accompanied by lack
      of understanding and social ostracism. In the second examination there was
      selective improvement of all parameters, significantly greater in patients
      without PTSD symptoms. The best effects were achieved in the reduction of social
      dysfunctions, the growth of purposeful social activity, and improvement in the
      type of support received, and a reduction of selected parameters of social
      isolation. CONCLUSIONS: The program here described is selectively effective for
      the social reintegration of TBI-patients, especially those without PTSD symptoms.

PMID- 20037501
TI  - The reliability of ELISA in predicting H. pylori infection in dyspeptic
      populations under age 45.
AB  - BACKGROUND: Dyspepsia is a common problem worldwide. Many dyspeptic patients have
      no alarm symptoms and are diagnosed by family doctors. Non-invasive testing of H.
      pylori is recommended in patients up to the age of 55. Testing of asymptomatic
      high risk groups is now being considered in many countries. The aim of the study
      was to compare the accuracy of serology tests (ELISA, HelicoTest) against the
      benchmark UBT (urea breath test) in the detection of H. pylori infection in young
      populations. MATERIAL/METHODS: The study was conducted on 238 patients under age
      45 (159 with undiagnosed dyspepsia and 79 controls). The gold standard of
      diagnosis of H. pylori infection was based on a positive UBT. UBT, serological
      ELISA and HelicoTest were performed on each of the patients. RESULTS: By UBT
      50.9% and by ELISA 49.7% of dyspeptic patients were infected with H. pylori,
      while in the control group 38% and 39.2% were infected, respectively. HelicoTest
      showed the highest positive results in both groups (55.3% study group, 44.3%
      control). The average level of IgG antibodies from ELISA testing among patients
      with a positive UBT H. pylori result was 3.16 U/ml. Patients with negative UBT
      results showed an average IgG level of 0.53 U/ml. CONCLUSIONS: There was a
      correlation of increasing antibody level on ELISA and probability of testing
      positive on UBT. The majority of patients had moderate dyspeptic symptoms. The
      ELISA is an easy, cheap and effective method for diagnosing H. pylori infection
      in the primary care setting.

PMID- 20037503
TI  - Antioxidant therapy in human endocrine disorders.
AB  - Reactive oxygen species (ROS) have deleterious or beneficial effects; this dual
      nature of ROS means that ROS act as intracellular signaling molecules and as
      defense mechanisms against micro-organisms. An overproduction of ROS results in
      oxidative stress, a deleterious process that damages cell structures, including
      lipids, proteins, and DNA. Oxidative stress plays a major role in various human
      disease states, including endocrine dysfunction. As a safeguard against oxidative
      stress, several endogenous nonenzymatic and enzymatic antioxidant systems exist.
      Antioxidants can delay or prevent oxidative stress and are widely used in the
      hope of maintaining health and preventing diseases. Although early studies
      suggested that antioxidant supplements promoted health, later clinical trials
      revealed that it may not be true in all cases. In this article, we provide a
      brief review of the pathophysiologic aspects of oxidative stress in a number of
      the most commonly human endocrionopathies (diabetes, male and female infertility
      and thyroid diseases) and review the therapeutic potentials of existing
      antioxidant strategies. We focus on human clinical trials and discuss the
      implications of their results. Based on the data reported so far, we conclude
      that the results reported challenge us to design better antioxidant trials in
      future, with a particular emphasis on identifying 1) appropriate doses 2)
      selecting the right populations 3) treating for optimal durations and 4) specific
      intracellular targeting mechanisms.

PMID- 20037504
TI  - Challenges in economic evaluation of new drugs: experience with rituximab in
      Hungary.
AB  - BACKGROUND: Implementation of a new therapy into clinical practice is a complex
      process. Various countries have different requirements for information but most
      often focus on economic evaluation, which often plays a stronger role in
      healthcare decision making than does clinical evidence. MATERIAL/METHODS: To
      identify all potential challenges in economic evaluation, the case of a new
      biological drug, rituximab, used to treat rheumatoid arthritis, has been taken as
      an example. We present methods and results of economic assessment, highlighting
      the specific issues that should be considered in countries with economic and
      health care conditions similar to those of Hungary. RESULTS: In principle,
      economic evaluation requires data on characteristics of target population,
      disease progression, treatment impact, preferences, resource utilization and unit
      prices. Treatment effect/relative risk reduction and clinical practice patterns
      (resource use) may be more generalizable, whereas prices and baseline risk need
      to be jurisdiction specific. In order to address issues of transferability,
      investments need to be made in the collection of epidemiological and demographic
      data, plus data on clinical practice patterns, resource use, costs and health
      state valuation. In Hungary this problem has been solved through conducting a
      well designed 255 patient cross-sectional study. CONCLUSIONS: The Hungarian
      example shows that there should be more investment in data collection for those
      parameters that are thought to differ most from place to place. Owing to the
      similarities between Central and Eastern Europe countries in health care systems,
      clinical practice patterns and economic indicators, they may be able to develop
      partnerships to develop relevant regional databases and registries.

PMID- 20037505
TI  - [Surgical treatment of bronchiolo-alveolar cancer].
AB  - Bronchioloalveolar cancer (BAC) belongs to a high- grade differentiated lung
      adenocarcinoma, localizes in peripheral parts of the lung and demonstrates an
      intraalveolar growth. 21 patients with BAC has been operated during the period of
      1968-2008yy. It comprised 0,5% of the whole amount of patients operated on lung
      cancer. Diagnostics of BAC, especially its pneumonia-like form, is considered to
      be challenging and often belated. Though it was retrospectively proven, that BAC
      is characterized by a slow growth and rare involvement of lymph nodes. Lobectomy
      is considered to be a method of choice for the surgical treatment. Long-term
      treatment results are somewhat better then of other forms of non-small cell
      carcinoma of lung: of 21 radically operated patients, 11 are alive.

PMID- 20037502
TI  - Arterial baroreceptors in the management of systemic hypertension.
AB  - Hypertension is a multifactorial disease associated with significant morbidity.
      Increased sympathetic nervous system activity has been noted as an important
      etiologic factor and is, in part, regulated by afferent input arising from
      arterial and cardiopulmonary baroreceptors, activation of which causes inhibition
      of sympathetic output. It was thought for many years that baroreceptors control
      only short-term blood pressure changes, a conclusion stemming from observations
      in sinoaortic denervation (SAD) animal models and the phenomenon of rapid
      baroreceptor resetting, also seen in animal models. Newer observations, however,
      indicate that SAD is rather imperfect and resetting is rarely complete. Recent
      studies reveal that baroreceptors control sympathetic output on a more long-term
      basis and participate in fluid volume regulation by the kidney, and thus have the
      potential to adjust blood pressure chronically. Importantly, these findings are
      consistent with studies and observations in humans. Meanwhile, a model of
      electrical stimulation of the carotid sinus has been developed and successfully
      tested in animals. Following these encouraging results human trials to evaluate
      the clinical application of electrical carotid sinus manipulation in the
      treatment of systemic hypertension have commenced, and results so far indicate
      that this represents an exciting potential tool in the clinician's armament
      against chronic arterial hypertension.<br />

PMID- 20037506
TI  - [Long-term results of descending and thoracoabdominal aortic aneurisms
      treatment].
AB  - Long-term treatment results of 53 patients operated on thoracoabdominal aortic
      aneurisms and 7 patients, treated conservatively, were analyzed. Efficacy and
      choicelessness of operative treatment are demonstrated. 5-year general survival
      and complication free period for the operated patients were 0.59+/-0.09 and
      0,67+/-0,1, correspondingly. 10-year survival and complication free period was
      0.51+/-0.1 and 0,34+/-0,14. Unfavourable outcomes are cased by rupture or
      dissection of non-operated parts of aorta (40%); progressive coronary and carotid
      arteries occlusion (33,3%); septic complications (13,3%). Possibilities of long
      term outcomes improvement after operative treatment of thoracoabdominal aortic
      aneurisms are proposed.

PMID- 20037507
TI  - [Plastic surgery in patients with surgical wound infection].
AB  - Results of various skin plastic operations performed in 312 patients with soft
      tissue infection were analyzed. The choice of the method depended on size and
      site of the wound, predisposing pathological process, age and general patient's
      condition. Differential approach to the choice of reconstruction method allowed
      satisfactory short-term results in 91,4% of patients. 80% of patients
      demonstrated good long-term results.

PMID- 20037508
TI  - [Use of compression suturing device for colorectal anastomoses].
AB  - 78 patients with rectal cancer were operated on with the use of a new-generation
      compression suturing device for colorectal anastomosis. There were no
      complications and deaths postoperatively. Long-term follow-up revealed no
      contractures of the anastomotic zone. All patient demonstrated a satisfactory
      quality of life index after 6 months postoperatively.

PMID- 20037509
TI  - [Programmed relaparotomy in treatment of upper mesenteric artery acute
      occlusion].
AB  - Results of surgical treatment and frequency of intestinal necrosis in 44 patients
      with acute mesenterial circulation failure were analyzed. Instrumental method of
      detecting the border of necrosis by the infracted intestine should allow refuse
      programmed relaparotomies in treatment of such patients and perform a sole
      operation with intestinal resection and anastomosis.

PMID- 20037510
TI  - [Reglamentation of treatment of children with acute surgical diseases in general
      surgical departments for adults].
AB  - Almost 60% of children with acute surgical diseases are treated by general
      surgeons in district hospitals. Insufficient knowledge of the specific features
      of childhood leads to a large number of tactical and technical errors. Fifteen
      years ago regional administration issued regulation standards for district
      hospitals depending on their ability to provide emergency surgical care to
      children of different age and condition. It significantly improved the results of
      medical help in this group of patients.

PMID- 20037511
TI  - [Shock score and surgical tactics for thoracic injury treatment].
AB  - Results of surgical treatment of 216 patients with thoracic injuries were
      retrospectively analyzed. 111 (51,4%) were operated on with the use of open
      technologies, whereas the rest 105 (48,6%) patients were treated with the use of
      videothoracoscopy. Patients were divided into 2 groups according to the shock
      score value. Was demonstrated, that videothoracoscopic operation was reasonable
      by shock score value less then 1,5. In patients with the shock score value more
      then 1,5, open surgery was more appropriate. Success of videothoracoscopic injury
      repair is stipulated also by detailed preoperative diagnostics, detecting the
      extent of the injury of the thorax and wounds of other regions, requiring urgent
      treatment.

PMID- 20037512
TI  - [Diagnostic criteria of posttraumatic stress disorder].
AB  - The authors consider historical and diagnostic aspects of the origin of the
      posttraumatic stress disorder diagnosis (PTSD). Different criteria of PTSD
      presented in diagnostic systems ICD-10 and DSM (from DSM-III to DSM-IV-TR) are
      analyzed. Attention is drawn to diagnostic definition of "acute stress disorder"
      (ASD) and its place in the dynamics of PTSD: ASD, acute PTSD, chronic PTSD. The
      authors claim the existence of PTSD as a distinct diagnostic entity and note that
      there are substantial differences in the clinical interpretation of distinct
      psychopathological phenomena involved in the PTSD structure by different authors.

PMID- 20037513
TI  - [The problem of the nosological independence of posttraumatic stress disorder].
AB  - The author considers the problem of the nosological independence and diagnosis of
      posttraumatic stress disorder (PTSD) in the theoretical aspect from the position
      of multifactor character of the disease development. The corresponding issues are
      discussed on example of consequences of combat trauma (PTSD in combatants). The
      author presents original conceptions on the consequent development of pathos and
      nosos with regard to "combat" PTSD.

PMID- 20037514
TI  - [Peculiarities of clinical presentations of posttraumatic stress disorder and its
      treatment in different types of traumatic exposures].
AB  - The authors study the exposure to different extreme events on examples of two
      types of stress--combat stress and the liquidation of Chernobyl accident. Thirty
      combatants and 33 liquidators have been examined and treated. Peculiarities of
      the initial study of stress reactions and posttraumatic stress disorder (PTSD)
      due to its main diagnostic criteria have been analyzed in each group of subjects.
      The authors conclude that similar pathological states, including all symptoms of
      PTSD, develop in response to different stressful exposures. At the same time,
      there are significant phenomenological differences in syndromes that are
      determined by the character of stressful (traumatic) event. Issues of complex
      treatment of patients using psychotherapy and pharmacotherapy as well as
      approaches to rehabilitation and social support are discussed in details.

PMID- 20037515
TI  - [New approaches to the diagnosis of mental state of child victims of emergency
      situations].
AB  - The authors present the data on peculiarities of mental state and behavior of
      children from refugee families and forced migrants in international (combat)
      conflicts and principles of organization of their treatment and rehabilitation.
      Mental and behavioral disorders in distinct periods after psychic trauma (acute,
      subacute and remote periods) and their relation with age (children of preschool,
      school and adolescence age) as well as parent's behavior are described. The
      organization of help is considered in view of cooperation of physicians of
      different specialties (psychiatrists, psychotherapists), psychologists and social
      workers. General recommendations for aiding are presented.

PMID- 20037516
TI  - [Posttraumatic regression in children: data of the psychological work in Beslan
      in 2004-2006].
AB  - Peculiarities of one of the most typical consequences of children trauma,
      regression, i.e. returning to the forms of behavior typical for previous age
      periods, are described on the example of the examination and psycho-corrective
      work with children, victims of the terror act in Beslan (2004). Stages of
      rendering help to these children in the posttraumatic period (during two years)
      using game techniques, different pedagogic approaches, including the restoration
      of skills that a child had previously had, are considered. In all approaches, the
      cultural aspect is thought to be the most important.

PMID- 20037517
TI  - [Short-term crisis psychotherapy in children with posttraumatic stress disorder
      in the frames of the "Dobryakov-Nikol'skaya" rehabilitation model].
AB  - Peculiarities of the model of medical-psychological help elaborated by the
      authors are presented on the example of the psychotherapeutic work with children,
      victims of the terror act in Beslan. A complex of methods which includes
      "debriefing", and using of tails and games in the combination with the technique
      of serial drawings and stories was applied in accordance to rules of crisis
      psychotherapy. Results demonstrate that the methods described allow to get into
      contact to the child, discover and remove his/her emotional experience related to
      the traumatic situation.

PMID- 20037518
TI  - [Consequences of sexual abuse in children and adolescence].
AB  - To establish clinical and age peculiarities of psychogenic disorders in children
      and adolescence, victims of non-family abuse, 90 victims, aged from 5 to 18 years
      (29 boys and 61 girls) have been studied. On different stages of legally
      significant situation, they developed marked psychogenic states which met the
      following ICD-10 diagnosis: acute reaction to stress (item F43.0) in 84% of
      patients, PTSD (F42.1) in 14%; short-term depressive reaction (F43.20) in 34%;
      prolonged depressive reaction (F43.21)--in 24%; phobic anxiety disorders (F40)-
      in 16% minors (9-13 years); mixed disturbance of emotions and conduct (F43.25)-
      in 12% of minors. The age specifics of mental disorders included the domination
      of disorders of neurotic level and rudimentary psychopathological signs. The
      author emphasizes the double (nonspecific and specific) nature of sexual abuse in
      the formation of psychogenic disorders in children.

PMID- 20037519
TI  - [Subjective ratings of conditions and methods of combat stress reduction by
      combatants].
AB  - An aim of the study was to find stress reduction methods preferred by combatants.
      One hundred and nineteen servicemen who do contract military service in the North
      Caucasus were questioned. More than a half of them named the support of colleges
      in arms. The awareness of importance of their aid was correlated with the
      duration and intensity of experiencing combat stress. Every fifth combatant chose
      individual combat experience out of all methods. The longer was duration of
      service in a combat zone, the more increased the subjective significance of
      personal experience. More than a third of combatants considered alcohol and drugs
      as effective means for stress reduction. Veterans, who iteratively did military
      service in military zones and had been wounded, and direct participants of
      combats named these means even more often. Among those examinees who noted
      alcohol as an effective mean for stress reduction, 26.6% noted also drugs and 20%
      -sedatives. The author suggests that the interest of combatants in alcohol and
      any drug that has an effect on the mental state indicates the higher risk of
      taking other psychoactive drugs.

PMID- 20037520
TI  - [Peculiarities of mental disorders caused by stressful events in combatants who
      committed criminal actions].
AB  - An aim of the study was to find symptoms of posttraumatic stress disorder (PTSD)
      that had an effect on aggressive behavior in combatants and to elaborate
      rehabilitation measures for such behavior. One hundred and seventy-four veterans,
      aged 22-43 years who committed criminal actions, were examined. Aggressive
      criminal behavior was noted in veterans with long-term combat experience,
      especially in conditions of particular intensity (extreme severity) of combat
      stress. These people had difficulties in the adaptation to civil life due to the
      presence of PTSD and characteristic personality changes. In all cases, criminal
      actions have been committed under an acute stressful situation of different
      severity associated with the interpersonal conflict (immediately or gradually
      developed). In these conditions, some PTSD symptoms masked real details of psycho
      traumatic conflict situation creating the impression of relentless confrontation.

PMID- 20037521
TI  - [Psychopharmacotherapy of patients with posttraumatic stress disorder].
AB  - Based on literature data and own results, the author presents a general strategy,
      a methodology and methods of treatment of posttraumatic stress disorder (PTSD)
      with some groups of psychopharmacological drugs. Peculiarities of the treatment
      of acute reaction to stress and PTSD are noted. There are differences in
      effectiveness of psychopharmacotherapy of these states: positive results in the
      therapy of acute reaction to stress are achieved in 90% and in that of PTSD--in
      40-60%. Recommendations for the treatment of these states are presented.

PMID- 20037522
TI  - [The role of genotype-environment interactions in the development of symptoms of
      anxiety and depression related to the disease burden for family].
AB  - The association of 5-HTTLPR and Val66Met BDNF genotypes with symptoms of anxiety
      and depression related to stress caused by severe chronic psychiatric disease of
      a family member has been studied. Genotyping has been conducted in the group of
      214 unaffected parents of patients with schizophrenia and 100 healthy age-matched
      controls. The diplotype Met*ss was associated with higher scores of depressive
      symptoms as assessed by MMPI in the group of parents but not in the control
      group. The most marked differences were seen in the subgroup of parents whose
      children had the greatest severity of symptoms. The results suggest that the
      interaction of 5-HTT and BDNF genes may moderate the association between
      objective and subjective burden of disease.

PMID- 20037523
TI  - [Efficacy of gabapentin in patients with discogenic lumbosacral radiculopathy].
AB  - Optimal conservative therapy of discogenic lumbosacral radiculopathy is a matter
      of debates. Contemporary guidelines recommend measures that predominantly have an
      influence on nociceptive mechanisms. However the mixed nature of pain in patients
      with discogenic radiculopathy requires approaches used for treatment of
      neuropathic pain. We carried out an open pilot study on efficacy of the
      anticonvulsant gabapentin in 25 patients with discogenic lumbosacral
      radiculopathy who were divided into two groups (with duration of pain episode 1
      month or less and more than 1 month). Gabapentin was used in increasing doses up
      to 3600 mg/day. To the end of 8-week trial, the significant reduction of pain and
      restricted mobility was found. The reduction of symptoms was more rapid in the
      group with earlier onset of treatment. In both groups, the reduction of vertebral
      syndrome and neuropathic pain characteristics was noticed as well. The clinically
      significant effect was found in 59% of patients with early onset of treatment
      with gabapentin and in 51% of patients with later onset. These results suggest
      that early use of gabapentin (tebantin) holds promises for treatment of
      discogenic radiculopathy.

PMID- 20037524
TI  - [Non pharmacotherapeutic correction of cerebral disturbances in children with
      diabetes mellitus type I].
AB  - A study of psychoemotional, autonomous and cognitive parameters revealed
      disturbances of the functional state of the central and autonomous nervous system
      in 75% of children with diabetes mellitus type I. The application of transcranial
      methods (transcranial electrostimulation (TES) and transcranial magnetic therapy
      (TcMT) demonstrated the high effectiveness in relation to the cerebral
      disturbances. The significant improvement was noted in 71.7% of children. The
      best clinical effect was achieved for the combination of TES and TcMT with
      primary effect of TcMT on the autonomous status and TES--on the psychoemotional
      status of patients. The combination of TES and TcMT stopped autonomous paroxysms
      in 70% of children, arrested phobic disorders in 60% and signs of depression in
      60%. Positive changes in behavior and the increase of progress in studies were
      seen in 50% of patients. The improvement of EEG parameters, including the
      decrease of tau- and beta(1)-rhythms in frontal areas, the increase of alpha
      rhythm activity, was found in 67.5% of cases. These findings suggest the increase
      of reserve potential of the central nervous system and the balance of excitement
      and inhibition processes in the cerebral cortex.

PMID- 20037525
TI  - [Trimigren in stopping migraine attacks: an open prospective multicenter
      comparative study of rectal suppository and tablet forms of sumatriptan].
AB  - Efficacy and safety of sumatriptan in rectal suppository (50 mg) and tablet forms
      (50 mg) in stopping migraine attacks has been studied in 80 patients with
      migraine with or without aura. Dynamics of migraine pain intensity measured with
      the VAS 30 min, 1, 2, 6 and 24 h after the first dose of drug was a primary index
      of efficacy. Secondary indices were the VAS intensity of nausea, vomiting,
      photophobia, phonophobia, duration of each migraine attack, quality of life
      parameters of a patient during the migraine attack assessed with the 24-hour
      questionnaire, severity of migraine course on the MIDAS, percentage of patients
      with complete regression of migraine pain, at least in 2 out of 3 attacks. To
      assess drug safety, any adverse effects, data of instrumental methods (clinical
      and biochemical blood tests, clinical urine test), EKG were taken into account.
      Rectal suppository had the more rapid effect on headache reduction compared to
      tablets. Changes of intensity of concomitant symptoms (nausea, vomiting,
      photophobia, phonophobia) as well as other secondary indices of drug efficacy
      were similar in both groups. In the group treated with rectal suppository, 9
      (22.5%) patients had 12 adverse effects. In the group treated with tablets, 22
      adverse effects were noted in 15 (37.5%) patients. Adverse effects related to the
      cardio-vascular system were observed less often in the group treated with rectal
      suppository (6.6 and 32%, respectively, p=0,004).

PMID- 20037526
TI  - [Combined therapy of aggressive remitted multiple sclerosis with mitoxantrone in
      combination with copaxone].
AB  - Patients with so called aggressive multiple sclerosis were treated. The course of
      disease is considered aggressive if there are clinical and tomographic signs of
      high disease activity with the frequency of exacerbations not less than 3 during
      2 years. Nine patients with this course of disease were examined. They received a
      combined therapy including the induction phase in which immunosuppressive drugs
      played a key role, and a phase of supporting therapy with immunomodulators. A
      variant based on drugs with opposite mechanisms of action (mitoxantron and
      copaxon) was worked out for the most effective use of possibilities of combined
      therapy. Stabilization and improvement of a patient's state by 77.8%, along with
      a reduction of exacerbation frequency, was found.

PMID- 20037527
TI  - [Anticonvulsant and psychotropic effects of topamax capsules].
AB  - Anticonvulsant and psychotropic effects of "Topamax capsules"(TC) were compared
      to a traditional form of topiramate (TFT) and some other anticonvulsant drugs
      (ACD). Thirty-six patients (12 men and 24 women) with partial temporary epilepsy
      were examined. Sixteen patients received TFT in tablets and 20 patients received
      ACD before the beginning of the study. Drug effect was assessed by frequency of
      seizures and some neuropsychiatric parameters. The results revealed that TC was
      comparable to TFT and ACD in the reduction of seizures of any semiotics. After 3
      months of therapy, total MMSE scores increased from 27 to 28. There were less
      perseverant errors and more right responses in the WCST. Verbal fluency and
      memory measured with Sunderland test improved as well. TC led to decreased
      latencies of negative responses in the WCST and increased verbal fluency compared
      to TFT. Patients who received TFT prior to TC did fewer errors in the WCST than
      patients who received ACD prior to TC. Verbal fluency improved compared to
      patients who received other ACD. At the same time, a somewhat increase of
      paranoid signs on the scale SCL-90 was noted in the group treated with topiramate
      only. It has been concluded that TC has an activating effect on frontal brain
      areas.

PMID- 20037528
TI  - [Comparative morphometric analysis of structural organization of separate heads
      of the human lateral pterygoid muscle during prenatal period and the first 3
      years of the postnatal period].
AB  - It was discovered some features in structure and differentiation of different
      types of the muscular fibers in each of the two heads of the lateral pterygoid
      muscle during ontogenesis. Taken characteristics gave possibility to think about
      different functional significance of data of structure in action of the
      temporomandibular joint of a man.

PMID- 20037529
TI  - [Infra-red spectrometry in oral liquid study for diagnostic purposes].
AB  - Infra-red (IR) spectrometry of the saliva was done by means of specially
      developed hardware-software complex. It was established, that in 9 wide ranges of
      the IR-spectrum there were diverse fluctuations of transmittance that
      characterize intermolecular interactions of various molecules associated with
      water and metabolites of biological systems. The found fluctuations were
      characterized quantitatively by dispersion of transmittance coefficients. It gave
      chance on 9 values of the given values by means of multidimensional analysis
      (Mahalanobis distance and Bartlett's criteria) defined on various frequencies of
      spectrum in comparison with the standard, quantitatively characterize the state
      of biological liquid that can be used 4 diagnostic purposes.

PMID- 20037530
TI  - [Endodontic treatment of teeth with Cupral nanoimpregnation application and pins
      from polypropylene].
AB  - In experimental research on 52 removed teeth an opportunity of sharing of a
      technique nanoimpregnation dentin a root hydroxide cuprum-calcium (Cupral) and
      sealings root the channel with application polypropylene pins Flex Point Neo was
      studied. Before sealing of root channela in laboratory model there was carried
      out within 7 day galvanophoresis of hydroxide cuprum-calcium with the help of
      invented by author's galvanic pins. Then channels were sealed up by material
      Dentalis KEZ with polypropylene pins. Methods of dye microinfiltration and
      scanning electronic microscopy revealed high efficacy of the specified way of
      endodontic treatments, consisting in good hermetic sealing system of root
      channels. In addition the autors defined, that temperature sterilization and
      efforts to bend did not cause essential deformation of pins and they corresponded
      to the ISO requirements.

PMID- 20037531
TI  - [Morphometric and stereometric analysis of the masticatory muscles in cases of
      progeny].
AB  - The data of microscopic and ultramicroscopric analysis of the muscles of
      mastication were presented of 12 male patients with progeny. There were
      determined differentiating peculiarities of muscles fibers of masseter and medial
      pterygoid in cases of progeny. The results of comperative analysis showed some
      decreasing of muscular quota and increasing connective tissue's quota; some
      decreasing muscular fibers' diameters and quantity of blood capillaries; some
      increasing muscular fibers type I in the muscles of mastication in progeny cases.

PMID- 20037532
TI  - [Intraceptal anesthesia of lower and upper teeth].
AB  - Effectiveness of intraseptal anesthesia for dental caries and its complications
      in 154 patients of different sex and ages was studied. Arterial pressure and
      heart rate were investigated in all patients before and after intraseptal
      injection with the help of automated monitor. Complete pain relief was observed
      in 135 patiensts, incomplete - in 12 patients. Intraseptal injection didn't act
      in 7 cases. There was no difference between the anesthesia on mandibula and
      maxilla. This was simple and predictable technique strong reaction of
      cardiovascular system occurred.

PMID- 20037533
TI  - [Intraligamentous anesthesia of lower lateral teeth].
AB  - Effectiveness of intraligamentous anesthesia for caries and pulpitis in 83
      patients was studied. This was efficient and simple technique of anesthesia of
      lower lateral teeth. Pulpul analgesia occured almost immediately after the
      injection and was accompanied by minimum of subjective sensations in the mouth.
      Arterial pressure and heart rate were investigated in all patients before,
      immediately and in 15-20 min after the injection with the help of automated
      monitor. Intraligamentous anesthesia beeng a vascular method caused in
      hypertensive patients unpredictable arterial pressure elevations.

PMID- 20037534
TI  - [Articaine and adrenaline combinations efficacy for dental anesthesia].
AB  - 5 articaine preparations including besides 4% articaine with epinephrine 1:100
      000 and 1:200 000, 4% articaine with epinephrine 1:400 000, 2% articaine 1:200
      000 and articaine without a vasoconstrictor were investigated on 52 volunteers,
      dental students. It was established that new combinations of articaine with
      epinephrine had relatively high activity to anesthetize dental pulp which was
      comparable with classic agents but slightly inferior to them in all the criteria
      studied. Articaine without adrenaline had not practically induced pulpal
      analgesia.

PMID- 20037535
TI  - [Oral acid-basic balance peculiarities in patients with gastrointestinal tract
      pathology].
AB  - In clinical research condition of the acide-basic balance in an oral cavity of
      100 patients having diseases of a digestive path: gastro-esophagus reflux
      illness, a stomach ulcer of a stomach and a duodenal gut, nonspecific ulcer
      colitis and Crone disease was studied. Estiniated speed salivations, pH,
      amplitudes test saccharose and carbamide curves pH in mixed saliva and on
      surfaces of tongue. It was revealed, that at this pathology there was
      destabilization of systems of regulation of the acide-basic balance in an oral
      cavity, accompanied by increase of acide- and ammonia-producing of microflora
      activity, topographical redistribution of zones functional acidosis and alkalosis
      on surfaces of tongue. Correction of the revealed infringements demanded
      individual approach in each case. The used methods of pH-meter were sensitive
      enough and allowed to reveal and estimated changes of local homeostasis in oral
      cavity.

PMID- 20037536
TI  - [Bite wounds of maxillofacial area: situation analysis for the Tver region].
AB  - 489 cases of references concerning the bitten wounds of maxillofacial area for
      the period of 1998-2008 were analysed. The analysis has shown that 77 (15,7%)
      cases with localization of the bitten wounds on fase had long, serious functional
      - aesthetic infringements, and the majority of cultural and life conditions
      questions, analyzed behavioural aspects of the population of the Tver region,
      remained unresolved actual problem.

PMID- 20037537
TI  - [Lasers in maxillofacial and plastic surgery].
AB  - Experimental data were analyzed about CO(2)-laser use during the operations upon
      different tissues (skin, mucous membrane, muscles and bone tissue). The data
      about treatment more than 12 thousands patients with different diseases of
      maxillofacial region. The advantages of laser method were shown.

PMID- 20037538
TI  - [Results of employment and improvement of postresectional cheiloplasty method
      with full thickness layer of labio-buccal flaps].
AB  - Results of 128 findings on cheiloplasty with full thickness ayer of labio-buccal
      flaps were summarized by the autors. Esthetic and functional results of
      postresectional cheiloplasty with sliding of full-thickness labio-buccal flaps
      were preferable when central and labial defects 1/3-1/2 and central defect 2/3 of
      the lower lip were filled in. The investigators suggested their own modification
      of the metod which combines quality of reconstruction of muscular oral sphincter
      and advantages of given expansion of oral fissure. With the modified method
      better esthetic and functional results were obtained.

PMID- 20037539
TI  - [Clinical evaluation of prevalence of seborrheic keratosis of face and neck skin
      among oncological patients].
AB  - Clinical resuls of examination of 280 oncologic patients 51-60 are presented. The
      aim was to detect seborrheal keratosis of face and neck in these patients. 280
      patient of given age group of maxillo-facial department were controls. Two fold
      increase in the presence of seborrheal keratosis of face and neck in oncologic
      patients was found as compared to control group.

PMID- 20037540
TI  - [Review of conservative replacement methods of the included minor defects of
      dentitions].
AB  - The paper reports the review of replacement methods of one absent tooth. The
      study was an assessment of prosthetic work in 275 patients with similar
      diagnosis. The aim of the study was to compare the indications for different
      fixed appliances with adhesive bonding on the example of schematic clinical
      situations.

PMID- 20037541
TI  - [Arterial pressure dynamics in patients during prosthetic stomatological
      reception].
AB  - During prosthetic stomatological reception with the help of portable arterial
      pressure monitor Kardiotechnika-04AD-01 there were examined patients with normal
      blood pressure and arterial hypertension. The data were received confirming
      dependence of arterial pressure lifting with personal anxiety level. Conclusion
      was drown that close patient's examination was necessary before prosthetic
      stomatological reception.

PMID- 20037542
TI  - [Repeated full removable prosthetics making peculiarities in cases of mobile
      alveolar crest].
AB  - There were discussed repeated full removable prosthetics making peculiarities in
      42 patients with mobile alveolar crest. Positive results of the treatment
      testified to the efficacy of the suggested by the authors technique.

PMID- 20037543
TI  - [Fluoride content in potable water and drinks. Connection with dental caries
      prevention and dental fluorosis].
AB  - Content of fluoride by ion selective electrode in potable water (municipal water
      supply, bottled, from draw-wells and springs), in juices of industrial and
      compotes of domestic preparation, in drinks of various grades of the tea made by
      water with unequal contents of fluorine was analyzed. Fluoride entered organism
      of the population in non-control mode more often in minimum quantities that
      explained, in certain measures a wide caries incidence. Granting of the
      information upon concentration of fluorides in potable water, juices and drinks
      used by population would allow people to adjust this microelement intake in the
      organism with the purpose of preventing of dental caries and fluorosis.

PMID- 20037544
TI  - [Local oral cavity immunity in schoolchildren with alimentary organs pathology].
AB  - A number of oral cavity immunity indices in schoolchildren with alimentary organs
      pathology there was presented. It testified to pronounced limitation both
      adaptive possibilities and anti-infective resistance of oral tissues and organs
      in children with this somatic pathology.

PMID- 20037545
TI  - [Relevance of the chronic tonsillitis problem].
AB  - This study was designed to analyse dynamic characteristics of planned and
      emergency surgical care provided to patients with chronic tonsillitis (CT) in 3
      large hospital of Moscow during the period between 2002 to 2006. The number of
      planed surgical interventions for the treatment of chronic tonsillitis performed
      during 5 years decreased almost two-fold. In contrast, the total number of urgent
      operations for surgical drainage of paratonisillar abscess in all clinics of the
      city during the last 10 years increased by a factor of 2. Results of
      bacteriological studies of species composition of microflora in patients with CT
      suggest the relationship between the incidence of this pathology and acute
      rheumatic fever. Analysis of activities aimed at the prevention of chronic
      tonsillitis (based in the first place at specialized dispensary facilities) has
      demonstrated that the number of patients involved in relevant monitoring programs
      is rather small and those in need of radical sanation of inflammatory CT foci are
      not referred for surgical treatment at the early stages of the disease as
      required by the current diagnostic and therapeutic algorithm for the management
      of chronic tonsillitis.

PMID- 20037546
TI  - [Analysis of delayed consequences of lowered surgical activity for children with
      chronic tonsillitis].
AB  - Materials for the analysis of medical histories of the patients admitted for
      planned tonsillectomy and those in need of emergency surgical treatment for
      paratonsillar abscess were collected in the Department of Otorhinolaryngology,
      G.N. Speransky City Children's Clinical Hospital No 9 during the periods from
      1990 to 2007. Simultaneously, analysis of the work of the Departments of
      Cardiorheumatology and Nephrology of the same hospital was undertaken. It was
      shown that the reduction in the number of surgical interventions for the
      treatment of different forms of chronic tonsillitis in the last years resulted in
      the increased frequency of local complications and concomitant morbidity.

PMID- 20037547
TI  - [Laryngeal ultrasound studies: potential, prospects, limitations].
AB  - In the last years, laryngeal ultrasound has been finding increasingly wide
      application due to the growing availability of relevant up-to-date equipment,
      apparent technical simplicity and non-invasive character of the study. However,
      poor knowledge of the physical basis of this method coupled to ungrounded self
      confidence of the operators and uncritical treatment of the obtained findings may
      lead to the overestimation of the diagnostic potential of this sonographic
      technique. This paper is focused on disadvantages of ultrasound examination of
      the larynx and associated acoustic artefacts that can be taken for true abnormal
      structures. Attempts at qualitative and quantitative interpretation of such
      images are fraught with wrong conclusions.

PMID- 20037548
TI  - [Allergic rhinitis and concomitant ENT diseases at Rudny Altai].
AB  - High prevalence of allergic rhinitis with concomitant ENT abnormalities at the
      stage of remission or exacerbation was documented among residents of the Rudny
      Altai region. A total of 200 patients with allergic rhinitis were examined of
      whom 114 (57%) had concomitant ENT diseases both of allergic and non-allergic
      origin. Sensitization to the pollen of herbs and grasses was recorded most
      frequently whereas the contribution of allergic reactions to the pollen of trees
      and shrubs to overall morbidity was much less significant. Interestingly, very
      high sensitivity to the pollen of local allergenic flora was documented. Most
      patients with allergic reactions exhibited poly- and hypersensitization to
      seasonal allergic rhinitis. Peculiarities of sensitization spectra in patients
      with allergic rhinitis and concomitant ENT pathology of allergic and non-allergic
      etiology are discussed.

PMID- 20037549
TI  - [Specific immunological and morphological features of chronic rhinitis].
AB  - Samples of mucosal tissue from inferior nasal conchae for histological and
      immunological studies were collected during surgical intervention on 25 non
      allergic patients with different clinical and morphological forms of chronic
      hypertrophic rhinitis. It was shown that the pathological process extends over
      all structures of conchal mucosa, namely, epithelium, lamina propria, and
      cavernous sinuses. However, proliferative activity of the epithelium may be
      spared, the structure of vascular endothelium, basement membranes of epithelium,
      glands and blood vessels remains either normal or only slightly affected, IgA
      synthesis persists, and immunocompetent cells (CD45 RO(+) T-lymphocytes, CD20(+)
      B-lymphocytes, and CD68(+) macrophages) retain functional activity. Taken
      together, these findings suggest high regenerative potential of nasal mucosa and
      preservation of mechanisms of local protection including cellular and humoral
      immunity despite the on-going pathological process. It implies the necessity of
      great caution during surgical interventions.

PMID- 20037550
TI  - [Mucociliary clearance in chronic hypertrophic and chronic vasomotor rhinitis in
      the light of morphometric data].
AB  - This study included a total of 90 patients of whom 35 ones suffered chronic
      hypertrophic (CHR) and chronic vasomotor (CVR) rhinitis. All the patients were
      examined in the saccharine test and underwent morphometry for the measurement of
      the ciliary beating rate (CBR) and the magnitude of extrusion of ciliary
      epithelium. Saccharine transit time in the group of CHR patients was found to
      vary from 20 to 43 minutes and CBR to equal 3.75 Hz. All these patients showed
      enhanced epithelial extrusion. Saccharine transit time in patients with CVR
      increased up to 17-29 min, with CBR being decreased to a mean of 4.56 Hz in 33
      (60%) of them. In 22 (40%) cases of CVR, CBR remained normal. Interestingly,
      patients with CVR exhibited no signs of epithelial atrophy whereas most of them
      had reduced CBR.

PMID- 20037551
TI  - [Peculiarities of growth and development of cultured mucosal cells from the upper
      respiratory tract stimulated by growth factors].
AB  - Specific features of growth and development of cultured mucosal cells from the
      upper respiratory tract were studied during their in vitro stimulation by
      keratinocyte growth factor (KGF) and epidermal growth factor (EGF). Phenotypic
      composition and quantitative characteristics of cultured epithelial cells was
      investigated with the use of monoclonal CD49F antibodies and flow
      cytofluorometry. The culture technique makes it possible to obtain a large amount
      of cells for the evaluation of their pathological changes. Moreover, cell
      cultures can be used to restore lesioned mucosa of the upper respiratory tract
      both in experiment and under clinical conditions.

PMID- 20037552
TI  - [Specific ototoxic effects of monomycin in immature animals].
AB  - Dynamics of the hearing function was evaluated using immature animals based on
      the SSCP data. Morphological characteristics of the cochlear auditory ganglion
      were studied after administration of therapeutic doses of the ototoxic antibiotic
      monomycin. Untreated animals served as controls. The results of morphofunctional
      investigations were evaluated in comparison with the similar data obtained in
      adult cats after injection of the same doses of monomycin.

PMID- 20037553
TI  - [Clinical and anatomical characteristic of nasal injuries].
AB  - A fracture of nasal bones is becoming a very common injury due to the
      increasingly greater number of car accidents and aggravated criminal situation. A
      total of 500 cases of nasal fracture associated with external deformities were
      included in the present study. The following kinds of deformities were
      identified: unilateral retraction, lateral displacement of the entire dorsum of
      the nose, and depressed comminuted fracture. Rhinoscopy revealed in addition such
      abnormalities associated with septal fracture as submucous hemorrhage,
      pathological mobility of the pyramid, deflection of the nasal septum at an acute
      angle. All in all, four types of nasal septum fractures were distinguished
      depending on the shape and localization of the fracture line. Two of them
      resulted in marked impairment of nasal breathing while two others required
      surgical intervention in the acute period after the injury.

PMID- 20037554
TI  - [Surgical correction of nasal septum with the use of Perfoost allografts].
AB  - New partially demineralized Perfoost allografts were used for the treatment of
      nasal septum defects in 16 patients admitted to the Research and Clinical
      Otorhinolarygological Centre, Federal Healthcare and Social Development Agency,
      between January 2007 and November 2008. The length of the follow-up period varied
      from 6 months to 1 year 10 months. The plastic material manufactured in the form
      of plates of different size was obtained from the bank of autografts based at the
      Central Institute of Traumatology and Orthopedics. Long-term monitoring of major
      physiological functions of the nose and rhinopneumetric studies showed that that
      Perfoost allografts were well tolerated by the patients; their application
      ensured excellent functional and aesthetic outcome of surgical correction of the
      injured nasal septum in all cases under observation.

PMID- 20037555
TI  - [Peculiarities of diagnosis and surgical treatment of choanal polyps].
AB  - This paper summarizes the experience with the surgical treatment of choanal
      polyps by means of the endoscopic technique. The relevant studies have
      demonstrated high efficiency of endonasal endoscopic removal of choanal polyps.
      Morphological examination of the resected tissues revealed metaplastic
      transformation of respiratory epithelium into many-layer squamous epithelium with
      concomitant lymphostasis, a rise in the number of goblet cells, local
      epithalaxia, and stromal sclerosis of the polyps. The importance of complete
      removal of the affected mucosa is emphasized.

PMID- 20037556
TI  - [Application of acoustic analysis of the voice to diagnosis and treatment of
      functional dysphonia].
AB  - Acoustic analysis of the voice was used to facilitate diagnosis and to
      objectively evaluate results of the treatment of psychogenic dysphonia (PD) in 20
      women. The control group comprised 20 women showing no signs of laryngeal
      pathology. The following parameters were measure: jitter, shimmer, signal to
      noise ratio, and response in the voicing test. Other methods applied included
      laryngoscopy, videolaryngoscopy, and laryngostroboscopy. It was shown that
      hoarseness in patients with PD results from the disturbances of mechanisms
      controlling stability of phonation. This observation is confirmed by the results
      of the acoustic test. It is concluded that dysphonia confirmed in the acoustic
      test in the absence of organic changes in the larynx is caused by psychogenic
      factors. Acoustic analysis of the voice is indicated to objectively evaluate
      results of the treatment of psychogenic dysphonia.

PMID- 20037557
TI  - [Restoration of speech function in oncological patients with maxillary defects].
AB  - Speech quality was evaluated in 188 patients with acquired maxillary defects.
      Prosthetic treatment of 29 patients was preceded by pharmacopsychotherapy. Sixty
      three patients had lessons with a logopedist and 66 practiced self-tuition based
      on the specially developed test. Thirty patients were examined for the quality of
      speech without preliminary preparation. Speech quality was assessed by auditory
      and spectral analysis. The main forms of impaired speech quality in the patients
      with maxillary defects were marked rhinophonia and impaired articulation. The
      proposed analytical tests were based on a combination of "difficult" vowels and
      consonants. The use of a removable prostheses with an obturator failed to correct
      the affected speech function but created prerequisites for the formation of the
      correct speech stereotype. Results of the study suggest the relationship between
      the quality of speech in subjects with maxillary defects and their intellectual
      faculties as well as the desire to overcome this drawback. The proposed tests are
      designed to activate the neuromuscular apparatus responsible for the generation
      of the speech. Lessons with a speech therapist give a powerful emotional
      incentive to the patients and promote their efforts toward restoration of
      speaking ability. Pharmacopsychotherapy and self-control are another efficacious
      tools for the improvement of speech quality in patients with maxillary defects.

PMID- 20037558
TI  - [Dynamics of the otoscopic and audiologic picture in children with congenital
      isolated palatal clefts at different stages of surgical treatment].
AB  - This otoscopic study including tympanometry and the test for otoacoustic emission
      involved children since birth till the age of 1.5 years with an isolated grade II
      (n=16) and III (n=20) palatal cleft. The patients were examined before and at
      different stages of surgical treatment. Normalization of the otoscopic picture
      and functional capacity of the Eustachian tube was achieved in 70% of the
      children with congenital isolated palatal clefts due to the recovery of natural
      anatomic characteristics of palatal muscles following surgical intervention
      within the first year of life.

PMID- 20037559
TI  - [Quantitative assessment of pain tolerance].
AB  - Pain tolerance was assessed in 44 volunteers by the analysis of their reports
      during blood collection using a 12-point verbal rating scale. Thereafter, pain
      intensity in response to 5 successive pricks was measured with a mechanical
      algesimeter, and the participants of the study were asked to evaluate pain
      sensation based on a 0-100 score visual-analogous scale. The test was
      discontinued as soon as a patient reported painful feeling in excess of 50
      scores. Twenty nine patients passed all the five tests while 11, 2, and 2 were
      able to tolerate 4, 3, and 2 challenges respectively. It was shown that the
      results of self-evaluation of painful sensation based on the verbal rating scale
      correlated with the number of tolerated test challenges. There was no significant
      correlation between the described signs. It is concluded that the methods for the
      assessment of pain tolerance described in this paper make it possible to predict
      the behaviour of a group as a whole but not of individual subjects.

PMID- 20037560
TI  - [Efficiency of sinuforte in combined therapy of acute suppurative
      rhinosinusitis].
AB  - The objective of this study was to evaluate clinical efficiency and safety of
      combined therapy including systemic antibiotics, decongestants, and sinuforte in
      patients with acute suppurative bacterial rhinosinusitis. The patients allocated
      to two groups comprising 25 subjects each were treated for a total of 8 days.
      Those in the study group received sinuforte once daily, 10.0 g of amoxilav twice
      daily, and xylometazole (BID). Control patients were given only amoxilav and
      xylometazole at the same doses. Dynamics of subjective and objective signs of
      rhinosinusitis, the mucociliary transport rate, and tolerance of sinuforte were
      the main variables assessed in this study. The introduction of sinuforte into
      combined therapy was shown to significantly improve dynamics of subjective and
      objective signs of rhinosinusitis compared with control. Results of the treatment
      with sinuforte are described as excellent in 19 patients against 13 in the
      control group, as good in 4 and 9 patients and satisfactory in 3 and 2 ones
      respectively. None of the patients needed puncture of maxillary sinuses in the
      course of the treatment. The mucociliary transport time prior to therapy was
      estimated at 22.18+/-3.82 and 22.36+/-3.64 in the study and control groups
      respectively (the difference was insignificant at p>0.05) compared with 14.88+/
      3.12 and 16.02+/-3.98 min (p<0.01) on day 8 after the initiation of therapy. The
      tolerance of sinuforte was estimated at 5.64 based on the 10-score visual
      analogous scale. Results of the study confirm that treatment with sinuforte
      combined with antibiotics (amoxicillin and clavulante) is a safe and efficacious
      therapeutic modality for the patients with acute bacterial rhinosinusitis.

PMID- 20037561
TI  - [Event-related potentials - an objective tool for assessment of the speech
      understanding process. II. Syntactic potentials (ELAN, P600)].
AB  - Investigations into electrophysiological potentials reflecting the process of
      grammatical analysis of the speech structure revealed a positive wave with the
      latency of 600 ms and maximum amplitude within the parietal region (P 600 wave).
      Presumably, this wave can reflect some consciously controlled processes of re
      analysis and correction of grammatical and syntactic inconsistencies. It can be
      used for the diagnosis of speech disorders.

PMID- 20037562
TI  - [Perinatal neurology - problems and solutions].

PMID- 20037563
TI  - [Age-related aspects of paroxysmal mental disorders in the debut of epilepsy].
AB  - Seventy-four patients with paroxysmal mental disorders in the debut of epilepsy
      have been examined. To study an age-related aspect of these disorders, all
      patients have been stratified by age at debut of epilepsy into 3 subgroups
      (children, adolescence and adult age). Based on a key psychopathological
      syndrome, three types of simple and complex partial "psychiatric" seizures have
      been singled out. The higher is the age of debut, the higher are the variability
      of clinical presentations of psychopathological disorders and more complex
      clinical presentations of complex partial (psychomotor) attacks in the structure
      of simple partial seizures. In children aged 7-14 years and people older than 18
      years, the simple partial "psychiatric" seizures as well as first manifestations
      of disease were seen more often than in adolescents. This type of debut was not
      observed in children younger than 7 years. The age curve of debut of epilepsy
      with complex partial seizures has two distinct peaks, at the children (up to 7
      years) and adult ages. In the group older than 18 years, frequencies of
      psychomotor seizures and first disease manifestations are inversely correlated
      with age.

PMID- 20037564
TI  - [Clinical-neurophysiological aspects of suicidal behavior].
AB  - Eighty-two patients with depression with suicidal tendencies, 82 patients without
      these tendencies and 150 healthy people have been studied. An attempt has been
      made to reveal a correlation of results obtained in calculating the entropy and
      information saturation of EEG with signs of dysontogenesis in patients with
      depression with- or without suicidal signs. In patients with depressive symptoms
      and feelings of despair, the ability to process information in the prefrontal
      cortex went down; at the same time, a portion of information saturation of
      occipital regions significantly increased. In depressive patients with suicidal
      ideation, there was a statistically significant <<flooding>> of the brain with
      excessive amount of information. A total elevation of information processing
      activity in all cortical areas, especially in frontal and medial temporal areas
      and right occipital regions as well, to emotionally neutral stimulus was noticed
      in patients without suicidal signs. An increase of information saturation in
      frontal and medial temporal cortex areas, especially in the left side, to
      emotionally positive stimulation was shown. The similar but less marked changes
      were found for negative stimulus. The decrease of prefrontal cortical activity
      observed in this group did not reach the level of significance and was noticed,
      in contrast to healthy people, for both positive and negative (more
      significantly) stimulation. The study of suicide attempters revealed the same
      results, with more significant decreasing of information saturation to
      emotionally neutral stimulus in frontal cortical areas as compared to the
      positive and negative stimulation. The significant difference was found for the
      right frontal temporal cortical area. An analysis of EEG changes in view of
      dysontogenetic factors suggests that these factors lead to the dysfunction of
      mesodiencephal structures due to mechanisms of plasticity. The irritation of
      these structures lead to disturbances in information processing that might cause
      clinical and psychological changes resulted in the suicide.

PMID- 20037565
TI  - [Neurophysiological and neurohistological analysis of striatal hyperkineses in
      the treatment with stereotaxic method].
AB  - A stereotaxic method has been used for the electrostimulation with the following
      electrolytic destruction of brain structures in 86 patients (54 male and 32
      female, aged from 6 to 52 years). The sample included 16 patients with torsion
      dystonia, 36 - with athetosis, 25 - with choreoathetosis and 9 with Huntington's
      chorea. The decrease of intensity of hyperkineses has been achieved in 81% of
      patients, no effect has been found in 19%, 1 patient died. Striatum, thalamus,
      motor and premotor neocortex, Cajal nucleus, dentate nucleus of cerebellum,
      subthalamic area (fields H7 and H2 of Forel) were used as stereotaxic targets.
      Data on the neurophysiological basis of changes of the pathological impulsion
      underlying hyperkineses are obtained. This finding has been confirmed by some
      neurohistological signs.

PMID- 20037566
TI  - [Levetiracetam (keppra) in the treatment of different epileptic syndromes in
      adults].
AB  - One hundred and thirty-eight patients (76 women and 62 men, aged from 16 to 65
      years) with symptomatic partial epilepsy (n=128) and idiopathic generalized
      epilepsy (n=10) have been studied. All patients received keppra on regiments of
      monotherapy (n=30) and polytherapy (n=108). The study included evaluation of
      anamnesis, clinical and neurophysiological examination, routine EEG and/or video
      EEG-monitoring, MRI of the brain, assessment of effectiveness, tolerability and
      quality of life (QUALIE-31, version 1). The period of observation was 1-4 years
      (on average 2,5 years). The high effectiveness and tolerability, good
      characteristics of therapy duration, the early appearance of clinical effect
      after the therapy has been started and positive cognitive effect are noted. The
      effectiveness, tolerance and clinical features of keppra treatment in different
      epileptic syndromes are analyzed.

PMID- 20037567
TI  - [Vitamin B complex (milgamma) in the treatment of vertebrogenic lumbosacral
      radiculopathy].
AB  - An open controlled study of efficacy of the vitamin B complex (milgamma) has been
      performed in 38 patients with vertebrogenic lumbosacral radiculopathy suffered
      from moderate or severe pain during 1 month or longer. Patients have been
      randomized into 2 equal groups: in the main group milgamma has been prescribed in
      the combination with diclofenac; patients of the control group have received
      diclofenac only. Treatment efficacy has been assessed by clinical scales in the
      10th and 24th days, and by the results of telephone interview after 3 and 6
      months. A trend to higher efficacy of the treatment of the main group compared to
      that of the control group assessed with the Visual Analogue Scale was observed
      during all the study but the difference reached the level of statistical
      significance only to the 24th day. The assessment of qualitative characteristics
      of pain with the Neuropathic Pain Scale revealed decreasing of intensive, acute
      and sensitive pain only in patients of the main group. The moderate or
      substantial improvement was noted in 66% patients received the combination
      therapy and only in 34% patients received diclofenac. At the 3rd months, between
      group differences were still significant (the pain was absent or minimal in 63%
      patients of the main group and 34% of the control one). The results revealed the
      potentiation of analgesic effect of diclofenac by the vitamin B complex. Using of
      milgamma in combination with NSAIDS leads to the rapid and long-standing regress
      of pain syndrome in patients with lumbosacral radiculopathy.

PMID- 20037568
TI  - [Comparative efficacy and tolerability of carbamazepine and oxcarbazepine during
      long therapy of patients with bipolar and schizoaffective disorders].
AB  - An aim of the study was to adjust the technique of using oxcarbazepine (OCB) and
      to study its preventive action and tolerability compared to carbamazepine (CBM)
      in patients with bipolar and schizoaffective disorders. The study included 48
      patients (7 male and 41 female), aged from 18 to 70 years, with phasic psychoses
      (bipolar disorder, type I - 29 patients and schizoaffective disorder - 19
      patients). Patients were randomized into 2 treatment groups: 1 - 28 patients who
      received CBM in doses 300-1600 mg/day (mean 700+/-120 mg/day) during 25,43+/-2,34
      months; 2 - 20 patients who received OCB in doses 600-1800 mg/day (mean 900+/-145
      mg/day) during 12+/-0,65 months. Duration of affective symptoms during the
      preventive therapy with CBM was reduced by 50,1% and that for OCB - by 49,1%; a
      number of episodes decreased by 34,6 and 35,1%, respectively. A significant
      effect, i.e. complete stopping of phases, was found in 35,7% of patients of the
      CBM group and in 40% of patients of the OCB group. The drugs had approximately
      equal preventive efficacy in regard to depressive and mania phases and episodes
      of schizoaffective disorders as well. Moreover, both drugs were clearly able to
      stop the rapid cyclic course of bipolar affective disorder. Side-effects were
      seen in 67,86% of patients treated with CBM and 55% of patients treated with OCB.
      Preventive features of OCB were comparable to those of CBM for intensity and
      spectrum of action. The adjustment of doses for OCB therapy does not need any
      significant correction, the drug causes less side-effects and subjectively is
      better tolerated by patients.

PMID- 20037569
TI  - [Pathogenetic mechanisms of traumatic brain disease and main lines of their
      treatment].
AB  - To assess efficacy and tolerability of axamon (ipidacrine) in the complex therapy
      of patients with cranial-brain injuries, 40 patients have been studied. Patients
      of the main group (20 persons) received, along with traditional therapy, axamon
      in dose 0,02 g 3 times daily during 2 months and patients of the control group
      (20 persons) received only traditional therapy. Clinical examination and
      assessment with NIS, Autonomic Symptoms Questionnaire, Hamilton anxiety scale,
      electrophysiological study (magnetic diagnostics, electroneuromyography with
      investigation of somatosensory evoked potentials, brain CT (MRI) have been
      conducted at the beginning of treatment and 1 and 2 months after. Axamon
      demonstrated the highest efficacy (p<0.05) in stopping anxiety symptoms in
      patients of the main group in the 1st month of treatment. After 2 months, a
      significant improvement of patient's state in the main group assessed by NIS and
      Hamilton anxiety scale (p<0.05) was found. Data of electrophysiological and
      neuroimaging study revealed significant positive changes reflected in the
      normalization of intracerebral conductance and resolution of structural changes
      of brain substances in the injury. Side-effects of the drug were brief and did
      not lead to stopping treatment.

PMID- 20037570
TI  - [Platelet peculiarities in chronic schizophrenic patients].
AB  - A comparative study of the platelet resistance to different effects was conducted
      in patients with chronic schizophrenia and healthy controls using column
      chromatography on sepharose CL-2B with the incubation at 5 degrees C during 18 h.
      This method allows to reveal the greater platelet activation in patients compared
      to the controls. The platelet number in platelet rich plasma (PRP) obtained by
      centrifugation was 1,8 times less in male patients with chronic schizophrenia
      than in the controls. This considerable decrease of platelet number in patients
      may be associated with the platelet deficiency in the blood stream and/or the
      destruction of activated platelets during blood sampling and centrifugation for
      the PRP preparation.

PMID- 20037571
TI  - [Clinical and neurophysiological manifestations of cerebral asymmetry in cervical
      dystonia].
AB  - Based on the analysis of clinical and neurophysiological data with the use of up
      to-date methods of EEG processing, the authors discuss a role of cerebral
      asymmetry (CA) in the pathogenesis of cervical dystonia (CD). Sixty-seven
      patients (31 male and 36 female) with CD have been studied. The pathological turn
      of the head to the right side (RT) was observed in 34 patients, to the left side
      (LT) - in 33 patients. The uni- or bilateral generalization of dystonic symptoms
      (Meig's syndrome, laterocollis) was found only in one-third of RT patients. The
      visual analysis of EEG of RT patients revealed the high level of EEG
      synchronization with signs of cortical irritation, with the prevalence in the
      left hemisphere, and the presence of focal epileptiform appearances in the
      temporal leads of the left or both hemispheres with the left-side prevalence. In
      LT patients, the EEG presentation was similar to normal but more often
      represented the variants of <<activated>> EEG-pattern. In these cases, the
      apparent manifestations of CA were not found. The coherent analysis revealed the
      formation of the network of <<strong>> coherent links, with bilateral spread, in
      RT patients. This may suggest the functional inequivalence of the peripersonal
      space of right and left hand and the dominate significance of striopallidar and
      thalamic structures of the left hemisphere for the total brain activity.

PMID- 20037572
TI  - [Association study of the SCN1 gene polymorphism and effective dose of
      lamotrigine].
AB  - An association between a polymorphism of the SCN1 gene, a therapeutical target of
      lamotrigine, and an effective dose (a blood plasma concentration) of the drug in
      patients with epilepsy has been studied. Fifty patients with different forms of
      epilepsy have been genotyped for the SCN1 IVS5N+5 G>A polymorphism using
      polymerase chain reaction. The distribution of allelic variants was as follows:
      23 patients had the mutant homozygous genotype (V/V), 20 - the heterozygous
      genotype Wt/V and 7 were homozygous for the wild allele (Wt/Wt). Mean lamotrigine
      doses were 85,7+/-7,4 mg/day for carriers of the Wt/Wt genotype, 113,75+/-7,13
      mg/day for the Wt/V genotype and 142,4+/-15,43 mg/day for the V/V genotype. Peak
      plasma concentrations corresponded to effective doses were 0,6+/-0,065 mg/ml for
      Wt/Wt, 0,96+/-0,1 mg/ml for V/V and 0,72+/-0,1 mg/ml for Wt/V. The hypothesis on
      the association between the SCN1 IVS5N+5 G>A polymorphism and the effective dose
      (concentration) of lamotrigine was confirmed. The significantly higher frequency
      of the SCN1A mutation in the group of patients with epilepsy compared to the
      control group of Caucasians (45,5 and 21,3%, respectively) implies that this
      polymorphism may contribute to the pathogenesis of epilepsy.

PMID- 20037573
TI  - MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a
      with tumor progression.
AB  - MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and
      apoptosis and can function as tumor suppressor genes or oncogenes. The role of
      miRNAs in neuroendocrine tumors such as ileal carcinoids is largely unknown. We
      examined the differential expression of 95 miRNAs by RT-PCR using the QuantiMir
      System in eight matching primary and metastatic carcinoid tumors from the ileum.
      All miRNAs chosen for the QuantiMir System array were based on their potential
      functions related to cancer biology, cell development, and apoptosis. The
      expression of miRNAs for the samples was normalized to miRNA-197, and the
      matching primary and metastatic tumors were compared. There was downregulation of
      miRNA-133a, -145, -146, -222, and -10b in all samples between the primary and
      matching metastatic tumors and upregulation of miRNA-183, -488, and -19a+b in six
      of eight metastatic carcinoids compared to the primary tumors. miRNA-133a was
      further analyzed by TaqMan real-time RT-PCR and northern hybridization using six
      additional matching primary and metastatic samples, which supported the PCR array
      findings. There were significant differences in miRNA-133a expression with
      downregulation in the metastasis compared to the primary in the eight original
      cases (P<0.009) and in the six additional cases used for validation (P<0.014).
      Laser capture microdissection and real-time RT-PCR analysis using normal ileum
      found miRNA-133a expression in normal enterochromaffin cells. In situ
      hybridization in normal ileum showed that some of the mucosal endocrine cells
      expressed miRNA-133a. Both primary and metastatic ileal carcinoid tumors
      expressed miRNA-133a by in situ hybridization. These results provide information
      about novel marker miRNAs that may be used as biomarkers and/or therapeutic
      targets in intestinal carcinoid tumors.

PMID- 20037574
TI  - Amyloid beta from axons and dendrites reduces local spine number and plasticity.
AB  - Excessive synaptic loss is thought to be one of the earliest events in
      Alzheimer's disease. Amyloid beta (Abeta), a peptide secreted in an activity
      modulated manner by neurons, has been implicated in the pathogenesis of
      Alzheimer's disease by removing dendritic spines, sites of excitatory synaptic
      transmission. However, issues regarding the subcellular source of Abeta, as well
      as the mechanisms of its production and actions that lead to synaptic loss,
      remain poorly understood. In rat organotypic slices, we found that acute
      overproduction of either axonal or dendritic Abeta reduced spine density and
      plasticity at nearby ( approximately 5-10 mum) dendrites. The production of Abeta
      and its effects on spines were sensitive to blockade of action potentials or
      nicotinic receptors; the effects of Abeta (but not its production) were sensitive
      to NMDA receptor blockade. Notably, only 30-60 min blockade of Abeta
      overproduction permitted induction of plasticity. Our results indicate that
      continuous overproduction of Abeta at dendrites or axons acts locally to reduce
      the number and plasticity of synapses.

PMID- 20037575
TI  - A single fear-inducing stimulus induces a transcription-dependent switch in
      synaptic AMPAR phenotype.
AB  - Changes in emotional state are known to alter neuronal excitability and can
      modify learning and memory formation. Such experience-dependent neuronal
      plasticity can be long-lasting and is thought to involve the regulation of gene
      transcription. We found that a single fear-inducing stimulus increased GluR2
      (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2
      containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch
      in synaptic AMPAR phenotype was mediated by noradrenaline and action potential
      prolongation. The subsequent rise in intracellular Ca(2+) and activation of
      Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a
      switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable
      receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of
      hours. The change in glutamate receptor phenotype altered synaptic efficacy in
      cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a
      long-term change in synaptic receptor phenotype and may alter the activity of an
      inhibitory neural network.

PMID- 20037576
TI  - Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells.
AB  - Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb,
      whereas neocortical adult neurogenesis remains controversial. Several occurrences
      of neocortical adult neurogenesis in injured neocortex were recently reported,
      suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that
      can be activated by injury are maintained in the adult brain. However, it is not
      clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in
      the neocortical layer 1 of adult rats and observed that their proliferation was
      highly activated by global forebrain ischemia. Using retrovirus-mediated labeling
      of layer 1 proliferating cells with membrane-targeted green fluorescent protein,
      we found that the newly generated neurons were GABAergic and that the neurons
      were functionally integrated into the neuronal circuitry. Our results suggest
      that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions.

PMID- 20037577
TI  - HDAC1 nuclear export induced by pathological conditions is essential for the
      onset of axonal damage.
AB  - Histone deacetylase 1 (HDAC1) is a nuclear enzyme involved in transcriptional
      repression. We detected cytosolic HDAC1 in damaged axons in brains of humans with
      multiple sclerosis and of mice with cuprizone-induced demyelination, in ex vivo
      models of demyelination and in cultured neurons exposed to glutamate and tumor
      necrosis factor-alpha. Nuclear export of HDAC1 was mediated by the interaction
      with the nuclear receptor CRM-1 and led to impaired mitochondrial transport. The
      formation of complexes between exported HDAC1 and members of the kinesin family
      of motor proteins hindered the interaction with cargo molecules, thereby
      inhibiting mitochondrial movement and inducing localized beading. This effect was
      prevented by inhibiting HDAC1 nuclear export with leptomycin B, treating neurons
      with pharmacological inhibitors of HDAC activity or silencing HDAC1 but not other
      HDAC isoforms. Together these data identify nuclear export of HDAC1 as a critical
      event for impaired mitochondrial transport in damaged neurons.

PMID- 20037578
TI  - The descending corticocollicular pathway mediates learning-induced auditory
      plasticity.
AB  - Descending projections from sensory areas of the cerebral cortex are among the
      largest pathways in the brain, suggesting that they are important for subcortical
      processing. Although corticofugal inputs have been shown to modulate neuronal
      responses in the thalamus and midbrain, the behavioral importance of these
      changes remains unknown. In the auditory system, one of the major descending
      pathways is from cortical layer V pyramidal cells to the inferior colliculus in
      the midbrain. We examined the role of these neurons in experience-dependent
      recalibration of sound localization in adult ferrets by selectively killing the
      neurons using chromophore-targeted laser photolysis. When provided with
      appropriate training, animals normally relearn to localize sound accurately after
      altering the spatial cues available by reversibly occluding one ear. However,
      this ability was lost after eliminating corticocollicular neurons, whereas normal
      sound-localization accuracy was unaffected. The integrity of this descending
      pathway is therefore critical for learning-induced localization plasticity.

PMID- 20037579
TI  - Representing information in cell assemblies: persistent activity mediated by
      semilunar granule cells.
AB  - Here we found that perforant path stimulation in rat hippocampal slices evoked
      long-lasting barrages of synaptic inputs in subpopulations of dentate gyrus mossy
      cells and hilar interneurons. Synaptic barrages triggered persistent firing in
      hilar neurons (hilar up-states). We found that synaptic barrages originate from
      semilunar granule cells (SGCs), glutamatergic neurons in the inner molecular
      layer that generate long-duration plateau potentials in response to excitatory
      synaptic input. MK801, nimodipine and nickel all abolished both stimulus-evoked
      plateau potentials in SGCs and synaptic barrages in downstream hilar neurons
      without blocking fast synaptic transmission. Hilar up-states triggered functional
      inhibition in granule cells that persisted for more than 10 s. Hilar cell
      assemblies, identified by simultaneous triple and paired intracellular
      recordings, were linked by persistent firing in SGCs. Population responses
      recorded in hilar neurons accurately encoded stimulus identity. Stimulus-evoked
      up-states in the dentate gyrus represent a potential cellular basis for
      hippocampal working memory.

PMID- 20037580
TI  - Reengineering a receptor footprint of adeno-associated virus enables selective
      and systemic gene transfer to muscle.
AB  - Reengineering the receptor footprints of adeno-associated virus (AAV) isolates
      may yield variants with improved properties for clinical applications. We
      generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence
      in a previously identified heparan sulfate receptor footprint with corresponding
      residues from other AAV strains. This approach yielded several chimeric capsids
      displaying systemic tropism after intravenous administration in mice. Of
      particular interest, an AAV2/AAV8 chimera designated AAV2i8 displayed an altered
      antigenic profile, readily traversed the blood vasculature, and selectively
      transduced cardiac and whole-body skeletal muscle tissues with high efficiency.
      Unlike other AAV serotypes, which are preferentially sequestered in the liver,
      AAV2i8 showed markedly reduced hepatic tropism. These features of AAV2i8 suggest
      that it is well suited to translational studies in gene therapy of
      musculoskeletal disorders.

PMID- 20037581
TI  - Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing
      cognition with improved safety.
AB  - Phosphodiesterase 4 (PDE4), the primary cAMP-hydrolyzing enzyme in cells, is a
      promising drug target for a wide range of conditions. Here we present seven co
      crystal structures of PDE4 and bound inhibitors that show the regulatory domain
      closed across the active site, thereby revealing the structural basis of PDE4
      regulation. This structural insight, together with supporting mutagenesis and
      kinetic studies, allowed us to design small-molecule allosteric modulators of
      PDE4D that do not completely inhibit enzymatic activity (I(max) approximately 80
      90%). These allosteric modulators have reduced potential to cause emesis, a dose
      limiting side effect of existing active site-directed PDE4 inhibitors, while
      maintaining biological activity in cellular and in vivo models. Our results may
      facilitate the design of CNS therapeutics modulating cAMP signaling for the
      treatment of Alzheimer's disease, Huntington's disease, schizophrenia and
      depression, where brain distribution is desired for therapeutic benefit.

PMID- 20037582
TI  - Nucleotide-resolution analysis of structural variants using BreakSeq and a
      breakpoint library.
AB  - Structural variants (SVs) are a major source of human genomic variation; however,
      characterizing them at nucleotide resolution remains challenging. Here we
      assemble a library of breakpoints at nucleotide resolution from collating and
      standardizing ~2,000 published SVs. For each breakpoint, we infer its ancestral
      state (through comparison to primate genomes) and its mechanism of formation
      (e.g., nonallelic homologous recombination, NAHR). We characterize breakpoint
      sequences with respect to genomic landmarks, chromosomal location, sequence
      motifs and physical properties, finding that the occurrence of insertions and
      deletions is more balanced than previously reported and that NAHR-formed
      breakpoints are associated with relatively rigid, stable DNA helices. Finally, we
      demonstrate an approach, BreakSeq, for scanning the reads from short-read
      sequenced genomes against our breakpoint library to accurately identify
      previously overlooked SVs, which we then validate by PCR. As new data become
      available, we expect our BreakSeq approach will become more sensitive and
      facilitate rapid SV genotyping of personal genomes.

PMID- 20037583
TI  - Transcriptional profiling of growth perturbations of the human malaria parasite
      Plasmodium falciparum.
AB  - Functions have yet to be defined for the majority of genes of Plasmodium
      falciparum, the agent responsible for the most serious form of human malaria.
      Here we report changes in P. falciparum gene expression induced by 20 compounds
      that inhibit growth of the schizont stage of the intraerythrocytic development
      cycle. In contrast with previous studies, which reported only minimal changes in
      response to chemically induced perturbations of P. falciparum growth, we find
      that approximately 59% of its coding genes display over three-fold changes in
      expression in response to at least one of the chemicals we tested. We use this
      compendium for guilt-by-association prediction of protein function using an
      interaction network constructed from gene co-expression, sequence homology,
      domain-domain and yeast two-hybrid data. The subcellular localizations of 31 of
      42 proteins linked with merozoite invasion is consistent with their role in this
      process, a key target for malaria control. Our network may facilitate
      identification of novel antimalarial drugs and vaccines.

PMID- 20037584
TI  - CD36 ligands promote sterile inflammation through assembly of a Toll-like
      receptor 4 and 6 heterodimer.
AB  - In atherosclerosis and Alzheimer's disease, deposition of the altered self
      components oxidized low-density lipoprotein (LDL) and amyloid-beta triggers a
      protracted sterile inflammatory response. Although chronic stimulation of the
      innate immune system is believed to underlie the pathology of these diseases, the
      molecular mechanisms of activation remain unclear. Here we show that oxidized LDL
      and amyloid-beta trigger inflammatory signaling through a heterodimer of Toll
      like receptors 4 and 6. Assembly of this newly identified heterodimer is
      regulated by signals from the scavenger receptor CD36, a common receptor for
      these disparate ligands. Our results identify CD36-TLR4-TLR6 activation as a
      common molecular mechanism by which atherogenic lipids and amyloid-beta stimulate
      sterile inflammation and suggest a new model of TLR heterodimerization triggered
      by coreceptor signaling events.

PMID- 20037585
TI  - CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell
      intrinsic and cell-extrinsic mechanisms.
AB  - The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self
      tolerance, but the mechanisms of its actions have remained controversial. Here we
      examined the antigen specificity of tissue-infiltrating CD4(+) T cells in Ctla4(
      /-) mice. After adoptive transfer, T cells isolated from tissues of Ctla4(-/-)
      mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues
      from which they were derived, which suggested reactivity to tissue-specific
      antigens. We identified the pancreas-specific enzyme PDIA2 as an autoantigen in
      Ctla4(-/-) mice. CTLA-4 expressed either on PDIA2-specific effector cells or on
      regulatory T cells was sufficient to control tissue destruction mediated by PDIA2
      specific T cells. Our results demonstrate that both cell-intrinsic and non-cell
      autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self
      antigen.

PMID- 20037586
TI  - Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C.
AB  - Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy
      characterized by limb, diaphragm and laryngeal muscle weakness. Two unrelated
      families with CMT2C showed significant linkage to chromosome 12q24.11. We
      sequenced all genes in this region and identified two heterozygous missense
      mutations in the TRPV4 gene, C805T and G806A, resulting in the amino acid
      substitutions R269C and R269H. TRPV4 is a well-known member of the TRP
      superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations
      caused marked cellular toxicity and increased constitutive and activated channel
      currents. Mutations in TRPV4 were previously associated with skeletal dysplasias.
      Our findings indicate that TRPV4 mutations can also cause a degenerative disorder
      of the peripheral nerves. The CMT2C-associated mutations lie in a distinct region
      of the TRPV4 ankyrin repeats, suggesting that this phenotypic variability may be
      due to differential effects on regulatory protein-protein interactions.

PMID- 20037587
TI  - Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by
      alterations in TRPV4.
AB  - Scapuloperoneal spinal muscular atrophy (SPSMA) and hereditary motor and sensory
      neuropathy type IIC (HMSN IIC, also known as HMSN2C or Charcot-Marie-Tooth
      disease type 2C (CMT2C)) are phenotypically heterogeneous disorders involving
      topographically distinct nerves and muscles. We originally described a large New
      England family of French-Canadian origin with SPSMA and an American family of
      English and Scottish descent with CMT2C. We mapped SPSMA and CMT2C risk loci to
      12q24.1-q24.31 with an overlapping region between the two diseases. Further
      analysis reduced the CMT2C risk locus to a 4-Mb region. Here we report that SPSMA
      and CMT2C are allelic disorders caused by mutations in the gene encoding the
      transient receptor potential cation channel, subfamily V, member 4 (TRPV4).
      Functional analysis revealed that increased calcium channel activity is a
      distinct property of both SPSMA- and CMT2C-causing mutant proteins. Our findings
      link mutations in TRPV4 to altered calcium homeostasis and peripheral
      neuropathies, implying a pathogenic mechanism and possible options for therapy
      for these disorders.

PMID- 20037588
TI  - Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA,
      scapuloperoneal SMA and HMSN2C.
AB  - Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and
      hereditary motor and sensory neuropathies (HMSN) are clinically and genetically
      heterogeneous disorders of the peripheral nervous system. Here we report that
      mutations in the TRPV4 gene cause congenital distal SMA, scapuloperoneal SMA,
      HMSN 2C. We identified three missense substitutions (R269H, R315W and R316C)
      affecting the intracellular N-terminal ankyrin domain of the TRPV4 ion channel in
      five families. Expression of mutant TRPV4 constructs in cells from the HeLa line
      revealed diminished surface localization of mutant proteins. In addition, TRPV4
      regulated Ca(2+) influx was substantially reduced even after stimulation with
      4alphaPDD, a TRPV4 channel-specific agonist, and with hypo-osmotic solution. In
      summary, we describe a new hereditary channelopathy caused by mutations in TRPV4
      and present evidence that the resulting substitutions in the N-terminal ankyrin
      domain affect channel maturation, leading to reduced surface expression of
      functional TRPV4 channels.

PMID- 20037589
TI  - A genome-wide perspective of genetic variation in human metabolism.
AB  - Serum metabolite concentrations provide a direct readout of biological processes
      in the human body, and they are associated with disorders such as cardiovascular
      and metabolic diseases. We present a genome-wide association study (GWAS) of 163
      metabolic traits measured in human blood from 1,809 participants from the KORA
      population, with replication in 422 participants of the TwinsUK cohort. For eight
      out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH
      and SLC16A9), the genetic variant is located in or near genes encoding enzymes or
      solute carriers whose functions match the associating metabolic traits. In our
      study, the use of metabolite concentration ratios as proxies for enzymatic
      reaction rates reduced the variance and yielded robust statistical associations
      with P values ranging from 3 x 10(-24) to 6.5 x 10(-179). These loci explained
      5.6%-36.3% of the observed variance in metabolite concentrations. For several
      loci, associations with clinically relevant parameters have been reported
      previously.

PMID- 20037590
TI  - Two-color, two-photon uncaging of glutamate and GABA.
AB  - We developed a caged GABA (gamma-aminobutyric acid), which, when combined with an
      appropriate caged glutamate, allows bimodal control of neuronal membrane
      potential with subcellular resolution using optically independent two-photon
      uncaging of each neurotransmitter. We used two-color, two-photon uncaging to fire
      and block action potentials from rat hippocampal CA1 neurons in brain slices with
      720-nm and 830-nm light, respectively. Our method should be generalizable to
      other chemical messenger pairs.

PMID- 20037592
TI  - Adaptive optics via pupil segmentation for high-resolution imaging in biological
      tissues.
AB  - Biological specimens are rife with optical inhomogeneities that seriously degrade
      imaging performance under all but the most ideal conditions. Measuring and then
      correcting for these inhomogeneities is the province of adaptive optics. Here we
      introduce an approach to adaptive optics in microscopy wherein the rear pupil of
      an objective lens is segmented into subregions, and light is directed
      individually to each subregion to measure, by image shift, the deflection faced
      by each group of rays as they emerge from the objective and travel through the
      specimen toward the focus. Applying our method to two-photon microscopy, we could
      recover near-diffraction-limited performance from a variety of biological and
      nonbiological samples exhibiting aberrations large or small and smoothly varying
      or abruptly changing. In particular, results from fixed mouse cortical slices
      illustrate our ability to improve signal and resolution to depths of 400 microm.

PMID- 20037591
TI  - Chronic microsensors for longitudinal, subsecond dopamine detection in behaving
      animals.
AB  - Neurotransmission operates on a millisecond timescale but is changed by normal
      experience or neuropathology over days to months. Despite the importance of long
      term neurotransmitter dynamics, no technique exists to track these changes in a
      subject from day to day over extended periods of time. Here we describe and
      characterize a microsensor that can detect the neurotransmitter dopamine with
      subsecond temporal resolution over months in vivo in rats and mice.

PMID- 20037593
TI  - A key role for orexin in panic anxiety.
AB  - Panic disorder is a severe anxiety disorder with recurrent, debilitating panic
      attacks. In individuals with panic disorder there is evidence of decreased
      central gamma-aminobutyric acid (GABA) activity as well as marked increases in
      autonomic and respiratory responses after intravenous infusions of hypertonic
      sodium lactate. In a rat model of panic disorder, chronic inhibition of GABA
      synthesis in the dorsomedial-perifornical hypothalamus of rats produces anxiety
      like states and a similar vulnerability to sodium lactate-induced
      cardioexcitatory responses. The dorsomedial-perifornical hypothalamus is enriched
      in neurons containing orexin (ORX, also known as hypocretin), which have a
      crucial role in arousal, vigilance and central autonomic mobilization, all of
      which are key components of panic. Here we show that activation of ORX
      synthesizing neurons is necessary for developing a panic-prone state in the rat
      panic model, and either silencing of the hypothalamic gene encoding ORX (Hcrt)
      with RNAi or systemic ORX-1 receptor antagonists blocks the panic responses.
      Moreover, we show that human subjects with panic anxiety have elevated levels of
      ORX in the cerebrospinal fluid compared to subjects without panic anxiety. Taken
      together, our results suggest that the ORX system may be involved in the
      pathophysiology of panic anxiety and that ORX antagonists constitute a potential
      new treatment strategy for panic disorder.

PMID- 20037594
TI  - Characterization of the human neutrophil alloantigen-3a.
AB  - Transfusion-related acute lung injury (TRALI) is a frequent cause of transfusion
      associated morbidity and mortality. Severe TRALI is often due to antibodies in
      blood components directed against the human neutrophil alloantigen-3a (HNA-3a).
      We show here that the HNA-3a antigen arises from a nucleotide polymorphism in the
      choline transporter-like protein-2 gene (SLC44A2), with the resulting variation
      at amino acid position 154 determining the reactivity of the protein with HNA-3a
      specific antibodies; the variant with an arginine at this position, rather than a
      glutamine, constitutes the HNA-3a antigen. The molecular identification of this
      antigen should facilitate the development of assays for blood donor screening to
      lower the risk of TRALI.

PMID- 20037595
TI  - Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7
      expression on dendritic cells and dampens antitumor responses.
AB  - Sterol metabolism has recently been linked to innate and adaptive immune
      responses through liver X receptor (LXR) signaling. Whether products of sterol
      metabolism interfere with antitumor responses is currently unknown. Dendritic
      cells (DCs) initiate immune responses, including antitumor activity after their
      CC chemokine receptor-7 (CCR7)-dependent migration to lymphoid organs. Here we
      report that human and mouse tumors produce LXR ligands that inhibit CCR7
      expression on maturing DCs and, therefore, their migration to lymphoid organs. In
      agreement with this observation, we detected CD83(+)CCR7(-) DCs within human
      tumors. Mice injected with tumors expressing the LXR ligand-inactivating enzyme
      sulfotransferase 2B1b (SULT2B1b) successfully controlled tumor growth by
      regaining DC migration to tumor-draining lymph nodes and by developing overt
      inflammation within tumors. The control of tumor growth was also observed in
      chimeric mice transplanted with bone marrow from mice lacking the gene encoding
      LXR-alpha (Nr1h3(-/-) mice) Thus, we show a new mechanism of tumor immunoescape
      involving products of cholesterol metabolism. The manipulation of this pathway
      could restore antitumor immunity in individuals with cancer.

PMID- 20037596
TI  - Loqs and R2D2 act sequentially in the siRNA pathway in Drosophila.
AB  - In Drosophila melanogaster, the small interfering RNA (siRNA) pathway is
      triggered by exogenous double-stranded RNA (dsRNA) or upon viral infection. This
      pathway requires Dicer-2 (Dcr-2) in association with a dsRNA-binding protein
      (dsRBP) called R2D2. A potentially distinct siRNA pathway, which requires Dcr-2
      in association with a different dsRBP, called Loquacious (Loqs), is activated by
      endogenous dsRNA derived from transposons, structured loci and overlapping
      transcripts. Here we show that different sources of dsRNA enter a common siRNA
      pathway that requires R2D2 and Loqs. R2D2 and loqs mutants show impaired
      silencing triggered by injection of exogenous dsRNA or by artificial and natural
      expression of endogenous dsRNA. In addition, we show that these dsRBPs function
      sequentially and nonredundantly in collaboration with Dcr-2. Loqs is primarily
      required for dsRNA processing, whereas R2D2 is essential for the subsequent
      loading of siRNAs into effector Ago-RISC complexes.

PMID- 20037597
TI  - STIM1 gates the store-operated calcium channel ORAI1 in vitro.
AB  - Store-operated Ca(2+) entry through the plasma membrane Ca(2+) release-activated
      Ca(2+) (CRAC) channel in mammalian T cells and mast cells depends on the sensor
      protein stromal interaction molecule 1 (STIM1) and the channel subunit ORAI1. To
      study STIM1-ORAI1 signaling in vitro, we have expressed human ORAI1 in a sec6-4
      strain of the yeast Saccharomyces cerevisiae and isolated sealed membrane
      vesicles carrying ORAI1 from the Golgi compartment to the plasma membrane. We
      show by in vitro Ca(2+) flux assays that bacterially expressed recombinant STIM1
      opens wild-type ORAI1 channels but not channels assembled from the ORAI1 pore
      mutant E106Q or the ORAI1 severe combined immunodeficiency (SCID) mutant R91W.
      These experiments show that the STIM1-ORAI1 interaction is sufficient to gate
      recombinant human ORAI1 channels in the absence of other proteins of the human
      ORAI1 channel complex, and they set the stage for further biochemical and
      biophysical dissection of ORAI1 channel gating.

PMID- 20037598
TI  - Prostate calculi in cancer and BPH in a cohort of Korean men: Presence of calculi
      did not correlate with cancer risk.
AB  - Prostatic calculi are common and are associated with inflammation of the
      prostate. Recently, it has been suggested that this inflammation may be
      associated with prostate carcinogenesis. The aim of this study was to investigate
      the relationship between prostatic calculi and prostate cancer (PCa) in prostate
      biopsy specimens. We retrospectively analyzed 417 consecutive patients who
      underwent transrectal ultrasonography (TRUS) and prostate biopsies between
      January 2005 and January 2008. Based on the biopsy findings, patients were
      divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect
      prostatic calculi and to measure prostate volume. The correlations between PCa
      risk and age, serum total PSA levels, prostate volume, and prostatic calculi were
      analyzed. Patient age and PSA, as well as the frequency of prostatic calculi in
      the biopsy specimens, differed significantly between both the groups (P < 0.05).
      In the PCa group, the Gleason scores (GSs) were higher in patients with prostatic
      calculi than in patients without prostatic calculi (P = 0.023). Using
      multivariate logistic regression analysis, we found that patient age, serum total
      PSA and prostate volume were risk factors for PCa (P = 0.001), but that the
      presence of prostatic calculi was not associated with an increased risk of PCa (P
      = 0.13). In conclusion, although the presence of prostatic calculi was not shown
      to be a risk factor for PCa, prostatic calculi were more common in patients with
      PCa and were associated with a higher GS among these men.

PMID- 20037599
TI  - Scoring of sperm chromosomal abnormalities by manual and automated approaches:
      qualitative and quantitative comparisons.
AB  - It is now well known that levels of sperm disomy correlate to levels of
      infertility (as well as other factors). The risk of perpetuating aneuploidy to
      the offspring of infertile males undergoing intracytoplasmic sperm injection
      (ICSI) has become a hotly debated issue in assisted reproduction; however, there
      remain barriers to the practical implementation of offering sperm disomy
      screening in a clinical setting. The major barrier is the operator time taken to
      analyze a statistically meaningful (sufficient) number of cells. The introduction
      of automated 'spot counting' software-hardware combinations presents a potential
      solution to this problem. In this preliminary validation study, we analyzed 10
      patients, both manually and using a commercially available spot counter. Results
      show a statistically significant correlation between both approaches for scoring
      of sperm disomy, but no correlation is found when scoring for diploid sperm. The
      most likely explanation for the latter is an apparent overscoring of two closely
      associated sperm heads as a single diploid cell. These results, and similar
      further studies that will ensue, help to inform cost-benefit analyses that
      individual clinics need to carry out in order to decide whether to adopt sperm
      aneuploidy screening as a routine tool for the assessment of sperm from men
      requiring ICSI treatment.

PMID- 20037600
TI  - c.822+126T>G/C: a novel triallelic polymorphism of the TSSK6 gene associated with
      spermatogenic impairment in a Chinese population.
AB  - TSSK6 is a member of the testis-specific serine/threonine kinase family. Male
      Tssk6 knockout mice are infertile owing to spermatogenic impairment, including
      sperm count reduction, a decrease in motile sperm number and motility rates, and
      an increase in the number of sperms with abnormal morphology. We investigated the
      possible association between variations of the TSSK6 gene and spermatogenic
      impairment in humans. Mutation screening of TSSK6 was carried out in 519 patients
      with azoospermia (n = 273) or severe oligozoospermia (n = 246) and in 359
      controls with normozoospermia by denaturing high-performance liquid
      chromatography and DNA sequencing. The frequencies of alleles and genotypes of
      gene polymorphism were compared between patients and controls. A novel triallelic
      polymorphism in TSSK6, c.822+126T>G/C, was identified. The frequencies of
      genotype TT and allele T were increased dramatically in infertile patients
      compared with controls, whereas genotype TG, allele G and allele C frequencies
      were significantly higher in controls than in patients. Further study revealed
      that the allele C frequency of controls was remarkably higher than that of
      patients with oligospermia. Our findings, for the first time, suggested an
      association of c.822+126T>G/C in TSSK6 with spermatogenic impairment in humans in
      which allele T may be a risk factor for male infertility, while alleles C and G
      may decrease susceptibility to male infertility.

PMID- 20037601
TI  - Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric
      adenocarcinoma AGS cells.
AB  - AIM: To investigate the effect of betulinic acid (BA) on the proliferation,
      apoptosis and cell cycle of gastric adenocarcinoma cell AGS in vitro and the
      underlying mechanism. METHODS: The effect of BA on the proliferation of AGS cells
      was measured by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
      (MTT) assay. Apoptosis was analyzed by using Annexin V-fluorescein isothiocyanate
      (FITC)/propidium iodide (PI) double-labeled flow cytometry (FCM) and Hoechst
      33258 staining. The influence of BA on cell cycle of AGS cells was tested by PI
      staining. Both FCM and reverse transcription-PCR (RT-PCR) technologies were
      applied to detect the expression of Hiwi and Cyclin B1. RESULTS: BA exhibited
      significant cell proliferation inhibition, as well as its potency of inducing
      apoptosis in AGS cells in vitro in a time- and dose-dependent manner. The IC(50)
      value for 24 h was 18.25 microg/mL (95% confidence interval: 15.16 to 27.31
      microg/mL). Cells treated with BA showed increased cell population in G(2)/M
      phase, with decreased S phase population. The expression of Hiwi and Cyclin B1
      was down-regulated in BA-treated AGS cells in a dose-dependent manner.
      CONCLUSION: BA exerted potent effect on growth inhibition, G(2)/M cell cycle
      arrest and induction of apoptosis in AGS cells in vitro, possibly associated with
      the down-regulation of Hiwi and its downstream target Cyclin B1 expression. The
      potent antitumor capacity of BA suggested that it could be a promising new
      experimental anticancer agent in human gastric adenocarcinoma treatment.

PMID- 20037602
TI  - PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis.
AB  - AIM: To study the probable mechanisms of the anti-glomerulosclerosis effects
      induced by peroxisome proliferator-activated receptor gamma (PPARgamma) agonists
      in rat intraglomerular mesangial cells (MCs). METHODS: Cells were transfected
      with the pTAL-PPRE-tk-Luc(+) plasmid and then treated with different
      concentrations of PPARgamma agonist, either troglitazone or telmisartan, for the
      indicated times. Promega luciferase assays were subsequently used for the
      detection of PPARgamma activation. Protein expression levels were assessed by
      Western blot, and PepTag assays were used for the non-radioactive detection of
      protein kinase A (PKA) activity. The deposition of alpha-smooth muscle actin
      (alpha-SMA) and p-cyclic AMP responsive element binding protein (pCREB) were
      analyzed by confocal laser scanning. RESULTS: Both troglitazone and telmisartan
      remarkably inhibit the PKA activation and pCREB expression that is stimulated by
      TGF-beta. The PPARgamma agonists also inhibited alpha-SMA and collagen IV protein
      expression by blocking PKA activation. CONCLUSION: PPARgamma ligands effectively
      suppress the activation of MCs and the accumulation of collagen IV stimulated by
      TGF-beta in vitro. The renal protection provided by PPARgamma agonists is partly
      mediated via their blockade of TGF-beta/PKA signaling.

PMID- 20037603
TI  - HIF-1alpha links beta-adrenoceptor agonists and pancreatic cancer cells under
      normoxic condition.
AB  - AIM: To examine whether beta-adrenoceptor (beta-AR) agonists can induce hypoxia
      inducible factor (HIF)-1alpha accumulation which then up-regulate the expression
      of its target genes in pancreatic cancer cells at normoxia, and to further
      elucidate the mechanism involved. METHODS: Pulse-chase assay, RT-PCR, and Western
      blot were employed to detect the effects of beta-AR agonists and antagonists,
      siRNA as well as several inhibitors of signal transduction pathways on MIA PaCa2
      and BxPC-3 pancreatic cancer cells. RESULTS: Treatment of pancreatic cancer cell
      lines with beta-AR agonists led to accumulation of HIF-1alpha and then up
      regulated expression of its target genes independently of oxygen levels. The
      induction was partly or completely inhibited not only by beta-AR antagonists but
      also by inhibitors of PKA transduction pathways and by siHIF-1alpha. Both beta1
      AR and beta2-AR agonists produced the above-mentioned effects, but beta2-AR
      agonist was more potent. CONCLUSION: Activation of beta-AR receptor
      transactivates epidermal growth factor receptor (EGFR) and then elicits Akt and
      ERK1/2 in a PKA-dependent manner, which together up-regulate levels of HIF-1alpha
      and downstream target genes independently of oxygen level. Our data suggest a
      novel mechanism in pancreatic cancer cells that links beta-AR and HIF-1alpha
      signaling under normoxic conditions, with implications for the control of glucose
      transport, angiogenesis and metastasis.

PMID- 20037604
TI  - Kruppel-like factor (KLF) 5 mediates cyclin D1 expression and cell proliferation
      via interaction with c-Jun in Ang II-induced VSMCs.
AB  - AIM: To elucidate how kruppel-like factor (KLF5) activates cyclin D1 expression
      in Ang II-induced vascular smooth muscle cells (VSMC) proliferation. METHODS: An
      adenoviral vector containing the full-length cDNA of KLF5 and a recombinant
      plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis
      were used to determine the effect of Ang II on cell growth. The luciferase assay
      and chromatin immunoprecipitation were used to detect the relationship between
      KLF5 and c-Jun in transactivation of cyclin D1 gene expression. RESULTS: Ang II
      upregulated the expression of KLF5 with concurrent acceleration of the cell cycle
      progression in VSMCs. Ang II induced KLF5 activation via the ERK and p38 MAPK
      pathways triggered by AT-1 receptor. High DNA binding activity and functional
      interaction of KLF5 and c-Jun were found in Ang II-induced VSMCs. Cotransfection
      of KLF5 and c-Jun expression vectors significantly increased cyclin D1 promoter
      activity. CONCLUSION: KLF5 is a downstream signal of the ERK 1/2 and p38 MAPK
      pathways, and activates the transcription of cyclin D1 gene via functional
      interaction with c-Jun in Ang II-induced VSMC proliferation.

PMID- 20037605
TI  - Application of RT-PCR in formalin-fixed and paraffin-embedded lung cancer
      tissues.
AB  - AIM: To analyze gene expression in formalin-fixed, paraffin-embedded lung cancer
      tissues using modified method. METHODS: Total RNA from frozen tissues was
      extracted using TRIZOL reagent. RNA was extracted from formalin-fixed, paraffin
      embedded tissues by digestion with proteinase K before the acid-phenol:chloroform
      extraction and carrier precipitation. We modified this method by using a higher
      concentration of proteinase K and a longer digestion time, optimized to 16 hours.
      RT-PCR and real-time RT-PCR were used to check reproducibility and the
      concordance between frozen and paraffin-embedded samples. RESULTS: The results
      showed that the RNA extracted from the paraffin-embedded lung tissues had high
      quality with the most fragment length between 28S and 18S bands (about 1000 to
      2000 bases). The housekeeping gene GUSB exhibited low variation of expression in
      frozen and paraffin-embedded lung tissues, whereas PGK1 had the lowest variation
      in lymphoma tissues. Furthermore, real-time PCR analysis of the expression of
      known prognostic genes in non-small cell lung carcinoma (NSCLC) demonstrated an
      extremely high correlation (r>0.880) between the paired frozen and formalin
      fixed, paraffin-embedded specimens. CONCLUSION: This improved method of RNA
      extraction is suitable for real-time quantitative RT-PCR, and may be used for
      global gene expression profiling of paraffin-embedded tissues.

PMID- 20037606
TI  - Integrating with integrity.

PMID- 20037607
TI  - No evidence for a role of CLCN2 variants in idiopathic generalized epilepsy.

PMID- 20037608
TI  - Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells.

PMID- 20037610
TI  - Evolutionary flux of canonical microRNAs and mirtrons in Drosophila.

PMID- 20037612
TI  - Exome sequencing makes medical genomics a reality.
AB  - Massively parallel sequencing of the exomes of four individuals with Miller
      syndrome, combined with filtering to exclude benign and unrelated variants, has
      identified causative mutations in DHODH. This approach will accelerate discovery
      of the genetic bases of hundreds of other rare mendelian disorders.

PMID- 20037613
TI  - Lung function and airway diseases.
AB  - Two studies report genome-wide association studies for lung function, using cross
      sectional spirometric measurements in healthy individuals. They identify six
      genetic loci newly associated to natural variation in lung function, which may
      have implications for the related airway diseases of asthma and chronic
      obstructive pulmonary disease.

PMID- 20037614
TI  - Getting connected in the globin interactome.
AB  - A new study provides compelling evidence that transcriptional regulation and
      three-dimensional genomic architecture are linked. The alpha- and beta-globin
      loci associate with hundreds of active genes across the genome at transcription
      factories in erythroid cells, and specialized Klf1-containing transcription
      factories mediate the association of Klf1-regulated genes.

PMID- 20037616
TI  - Educational intervention and the health seeking attitude and adherence to therapy
      by tuberculosis patients from an urban slum in lagos Nigeria.
AB  - BACKGROUND: Community based participation has been advocated by a number of
      international health organisations including the World Health Organization (WHO)
      as a solution to the problems of poor patient adherence and default from Directly
      Observed Treatment Short course [DOTs] programmes for tuberculosis control.
      OBJECTIVES: To determine the impact of a health educational intervention on the
      management of tuberculosis in relation to the outcome and adherence to therapy by
      Tuberculosis patients residing in a densely populated urban slum in Lagos,
      Nigeria. METHODS: The study was conducted using forty tuberculosis patients
      (confirmed by acid fast bacilli positive sputum), and selected randomly from
      those who attend the Mainland Hospital in Lagos. They were divided into two
      groups of twenty each made up of those to be provided with education intervention
      at the community level and the control groups followed up at the hospital level
      only. An initial assessment of the knowledge about tuberculosis management was
      done through a structured questionnaire for both groups. This was followed by
      continuous health talks for intervention group in form of neighbourhood self help
      approach. RESULTS: The results showed that the intervention had a significant
      impact on the understanding of disease and its management (X(2) =11.842 p<0.05),
      DOTS and increased awareness (X(2) =17.289 p<0.05, X(2) =10.461 p<0.05), knowing
      the side effects of anti-TB drugs (X(2) =10.157 p<0.05), the meaning of
      resistance to anti-Tuberculosis drugs (X(2) =19.798 p<0.05, X(2) =11.192 p<0.05)
      and importance of contact tracing (X(2) =32.4 p<0.05, X(2) =3.360 p<0.05).
      CONCLUSION: An effective health education is therefore beneficial for TB control
      in Nigeria.

PMID- 20037617
TI  - Improving supply of safe blood and reducing cost of transfusion service through
      haemovigilance.
AB  - Availability of safe blood remains a major challenge for many developing
      countries. Unnecessary discontinuation of scarce blood is a major conduit of
      wastage of scarce blood, as well as man hours and funds. Haemovigilance is a
      national system of surveillance and alarm, from blood collection to the follow-up
      of the recipients, gathering and analysing all untoward effects of blood
      transfusion in order to correct their cause and prevent recurrence. A prospective
      study to audit discontinuation of blood transfusion at the Obafemi Awolowo
      University Teaching Hospital Ile-Ife over a period of one and half years was
      done. Simple febrile non-haemolytic transfusion reaction (FNHTR) was the leading
      indication for such discontinuation (66.7%). More than half of discontinued
      transfusion due to FNHTR (58%) was successfully completed on review by trained
      personnel in transfusion medicine. A system of haemovigilance if incorporated
      into the blood transfusion service will promote effective monitoring of blood
      transfusion and reduce wastage of scarce blood/blood products.

PMID- 20037618
TI  - Assessment of preventive oral health knowledge and practices among rural and
      urban mothers in Lagos state.
AB  - AIMS AND OBJECTIVES: To evaluate students' performance and its predictors in the
      preclinical examinations at the College of Health Sciences, Ladoke Akintola
      University of Technology Ogbomoso Nigeria. MATERIALS AND METHODS: A cross section
      of students' records admitted into medical programme in 1999/2000 sessions was
      studied. RESULTS: Younger students performed consistently better than the older
      ones in all the three subjects taken at the MBBS1. It was also noticed that the
      male students performed better, a statistically significant mean difference in
      score was observed in Biochemistry P>0.05. Students with better Ordinary level
      aggregate grade of (5-15) in the five core subjects at SSCE, consistently had
      better results in all the subjects taken at MBBS1 examination compared to their
      counter-part with aggregate SSCE grade of (16-30). Students that were admitted
      through JAMB performed better in all the three subjects than those that were
      admitted through pre-degree programme and the transferred students. However, the
      mean difference was statistically significant P<0.05 in Biochemistry only.
      CONCLUSION: Better performance at MBBS1 was found in younger age group, those
      with aggregate grade of (5-15) in SSCE and those admitted through JAMB. Ordinary
      level requirement irrespective of the mode of admission should not be
      compromised. Schools that admit students through pre-degree, transfer or direct
      entry will have to be more conscious of the quality of students they admit and
      also operate such system with utmost transparency and with a principle of
      promoting good academic standard.

PMID- 20037619
TI  - Unsafe abortion in lagos, Nigeria: a continuing tragedy.
AB  - OBJECTIVES: To assess the incidence, pattern of presentation and management of
      complications resulting from unsafe abortion as well as the associated
      demographic variables at the Lagos Island Maternity Hospital. PATIENTS AND
      METHODS: A cross sectional survey of all cases with complicated induced abortion
      was carried out between 1st August 2005 and 31st January 2007. RESULTS: The
      majority of the patients were young 21.7% were teenagers between 14 and 19 years
      while 32.6% were in the 20-24 year age group. The majority (64.0%) were single
      while 30.9% were married, 1.7% were divorced, while 3.4% were separated.
      Teenagers and single women were more likely to obtain their abortion late (above
      12 weeks gestation). 81.2% of the patients knew about modern methods of
      contraception but only 34.5% had ever used contraception and only 8.6% were using
      contraception when they became pregnant. Medical doctors were the abortionists in
      46.9% of the cases, followed by nurses (17.7%) and traditional practitioners.
      Retained products of conception was the commonest complication (77.1%) followed
      by anaemia (48.6%) and sepsis (44.6%). Evacuation of the uterus was the commonest
      surgical procedure done. There were 16 maternal deaths giving a case fatality
      rate of 9.14%. Sepsis was the commonest cause of death. CONCLUSION: Unsafe
      abortion remains a serious concern to the health of women. Efforts need to be
      maximised at preventing unwanted pregnancy by making contraceptive services
      easily accessible to women. Effective post abortion care services need to be put
      in place.

PMID- 20037620
TI  - Eye health of professional drivers of a Nigerian University.
AB  - BACKGROUND: Safe driving and road traffic accident prevention could be attained
      through ensuring good condition of vehicles, the road as well as the physical and
      mental state of the driver among others Objectives: To determine the ocular
      health status of professional drivers of the University of Ibadan, Nigeria
      METHODS: A cross sectional survey of all drivers in the employment of the
      University of Ibadan, excluding the College of Medicine, was carried out between
      March and June 2002 at the University Medical Centre and the eye clinic of the
      University College Hospital, Ibadan. RESULTS: One hundred and ninety seven all
      male drivers were screened. Their ages ranged from 31 to 64 years (mean 48.3 +/
      5.9yr). Less than satisfactory presenting (functional) binocular visual acuity (<
      6/18) was found in 11(5.6%) of the drivers. With refraction no driver had
      binocular vision of <6/18, but three drivers each had corrected visual acuity in
      the worse eye of 6/12, 6/18 and 6/36 respectively. The commonest visual problems
      were presbyopia 100 (50.8%), and refractive errors 38 (19.3%). Other ocular
      pathologies included pterygium 11 (5.6%), optic atrophy 9 (5.0%), colour vision
      defects 7 (3.6%) cataract 2 (1.0%), age related macular degeneration 4 (2.0%),
      glaucoma 3 (1.5%) retinal scar 2 (1.0%), exotropia 1 (0.5%), and pingueculum 1
      (0.5%), CONCLUSION: Periodic screening of driver population of any establishment
      is a worthwhile task that may help to identify potentially blinding or visually
      impairing conditions such as glaucoma and refractive-error which can be promptly
      treated.

PMID- 20037621
TI  - Clinical experience with injectable progestogen- only contraceptives at
      University of Ilorin teaching hospital: a five year review.
AB  - OBJECTIVES: This is a retrospective study of 1,042 new acceptors of injectable
      progestogen-only contraceptives at the family planning clinic of the University
      of Ilorin Teaching Hospital over a five year period from 1st January 2001 to 31st
      December 2004. The total number of new clients seen during this period was 4,752.
      41.1% of these new clients chose condoms as a contraceptive method, 32.2%
      accepted IUCD, 21.9% accepted injectable progestogen-only contraceptive 08%
      accepted implants, 3.9% combined oral contraceptive pills and 0.1% bilateral
      tubal ligation. Of the acceptors of injectable progestogen, 59.5% used depo
      medroxyprogesterone acetate while 40.5% used norethisterone enanthate. 59.5% of
      the acceptors belonged to the 30 - 39 years age bracket and 36.2% were
      grandmultiparous women Injectable progestogen-only contraceptives are among the
      safest and most effective contraceptive methods available. The two commonly
      available types are Depot Medroxyprogesterone acetate and Norethisterone
      enanthate. This study looked at the clinical experience with this form of
      contraceptive at University of Ilorin Teaching Hospital (UITH). METHOD: The case
      notes of new clients that accepted injectable progestogen-only contraceptive at
      the family planning clinic of the UITH between June 2001 and December 2004 were
      analysed. RESULTS: Injectable progestogen-only contraceptive was the third most
      commonly accepted method of contraception at UITH during the study period. 59.5%
      of clients belonged to the 30-39 year age group, 63.5% of them were para 1-4 and
      36.2% were grandmultiparous women. 59.8% of the clients were educated up to the
      secondary level or above. There was no pregnancy reported during the study
      period. 29.9% of clients experienced various forms of side effects, the commonest
      of which was menstrual irregularities. CONCLUSION: Injectable progestogen-only
      contraceptive is widely accepted by women in this centre. Its use cuts across
      women of all age groups, parities, religion and level of education.

PMID- 20037622
TI  - Gastroduodenitis and Helicobacter pylori in Nigerians: histopathological
      assessment of endoscopic biopsies.
AB  - OBJECTIVE: Morphologic changes seen in the endoscopic biopsies are dynamic and
      could be predictive of more important sequelae of chronic H. pylori gastritis
      such as gastric carcinoma and lymphoma. The objective of the study was to review
      the biopsy appearances of endoscopic gastroduodenal biopsies using the updated
      Sydney System of classification in order to throw some light on the biology of
      gastroduodenitis. METHODS: A retrospective review of all endoscopic
      gastroduodenal biopsies received in the department of Morbid Anatomy of Obafemi
      Awolowo University Teaching Hospitals Complex between 1994 and 2003 was
      undertaken. Grading of the chronicity, activity, atrophy, H. pylori density and
      metaplasia were done using the updated Sydney System of classification and
      grading. RESULTS: A total of 1047 gastric and 47 duodenal biopsies from 1047
      patients were reviewed. There was evidence of significant chronic gastritis in
      98.1% of the gastric biopsies and in 78.0% of these, H. pylori was the main
      identifiable aetiological agent. Marked atrophic changes and intestinal
      metaplasia that are known to predispose to gastric malignances were seen in 4.9%
      and 9.3% of our cases respectively. Chronic duodenitis was seen in 83% of the
      duodenal biopsies and in 29.6%, H. pylori was seen on a background of gastric
      metaplasia. CONCLUSION: The prevalence of H. pylori was high and it was the
      single most important aetiological factor responsible for the biopsy changes
      associated with chronic gastroduodenitis.

PMID- 20037623
TI  - Acute appendicitis in Lagos: a review of 250 cases.
AB  - OBJECTIVES: Acute appendicitis is common. This prospective study of 250 cases of
      acute appendicitis was performed to critically analyse the pattern of
      presentation, management, operative findings and treatment outcome. The effect of
      length and position of the appendix in relationship to acute inflammation was
      also determined. PATIENTS AND METHODS: Two hundred and fifty cases of acute
      appendicitis were studied, including those found to have appendicitis at surgery
      despite other preoperative diagnosis. Patient biodata, clinical signs and
      symptoms were recorded. Haematological and biochemical parameters were determined
      after which all patients with a diagnosis of acute appendicitis had
      appendicectomy under general anaesthesia. All relevant peri-operative data were
      recorded. Excised appendices were sent for histological examination. RESULTS:
      There were 133 males and 117 females giving a gender ratio of 1.2:1. The mean age
      was 25.7 +/- 10.3 years, with majority of cases (42.8%) occurring in the third
      decade of life. Abdominal pain (100%), fever (48.4%), anorexia (48.0%), vomiting
      (47.8%) were the common symptoms. Commonly elicited signs included right iliac
      fossa direct tenderness (74.4%), rebound tenderness (59.2%), localised guarding
      (42.8%) and right rectal wall tenderness (43.2%). The mean white cell count was
      not significantly elevated (mean 8538 +/- 4166 per mm3, P > 0.05). Sixty three
      percent (156/245) of all appendices were retrocaecal in position. Mean length of
      the appendices was 10.4 +/- 2.9 cm. The length and position of appendices were
      not significantly different between those who had acutely inflamed and normal
      appendices (P = 0.923) Two hundred and forty five patients (98%) with a diagnosis
      of acute appendicitis had appendicectomy. The commonest postoperative
      complication was wound infection (8%), overall complication rate was 13.5% and
      negative appendicectomy rate was 13.4%. CONCLUSION: The presentation, management
      and treatment outcome of acute appendicitis in our centre are similar to those of
      other centres in our sub-region. Complication rates were low.

PMID- 20037624
TI  - Pulmonary manifestations of ankylosing spondylitis treated as pulmonary
      tuberculosis: a case report and review of literature.
AB  - A 45 year old trader presented with history of persistent productive cough,
      progressively increasing dyspnoea, malaise and fever of 6 months prior to
      presentations. He also complained of severe lower backache and stiffness that
      radiated to both legs of 5 years duration. Chest radiograph revealed left apical
      fibrosis, coarse, linear shadows with cavities. There was also super infection
      with aspergilloma in the left apical region. The sputum AAFB was negative.
      Despite the fact that the patient complained of lower backache and stiffness, the
      plain radiograph of the affected spine was not requested for by the attending
      physician. Rather, the patient was commenced on antituberculous therapy based on
      pulmonary changes on chest radiograph. But after completing the treatment (nine
      months regimen), there were no improvement in patient's clinical conditions and
      pulmonary changes on repeated chest radiograph. The plain radiographs of the
      lumbosacral spine, pelvis and both hips were suggested by the author
      (Radiologist) who reviewed the patient's chest radiographs. The radiographs of
      the lumbosacral spine, as well as pelvis and both hips showed features of
      ankylosing spondylitis with pulmonary complication. His treatment was later
      reviewed based on the above new findings. This report highlights the fact that
      pulmonary manifestation in ankylosing spondylitis, a rare entity in our
      environment can present the same pattern as pulmonary tuberculosis which is far
      more common in this environment. A high index of suspicion will enhance early
      proper diagnosis.

PMID- 20037625
TI  - [Chronic nephropathy in non-kidney transplantation: [prevention, early diagnosis
      and management].
AB  - Transplant from solid nonrenal organ has experienced an important increase in the
      last decades. It is due to the increasing improvement of the results obtained
      with the above mentioned transplants. Parallel, many nonrenal transplanted
      patients have developed a chronic renal failure that has determined, in some
      cases, the need of beginning the substitution of renal function by means of
      dialysis and/or transplant. The origin of the same one is multifactorial and the
      consequences derived from it are very important so much in morbimortality as of
      economic nature for the set of the system. The present review tries to help to
      the identification of risk factors of renal insufficiency in the nonrenal
      transplanted patient and to determine which might be the basic concepts of
      prevention, early diagnosis and of derivation to the nephrologist expert in
      transplants and renal dysfunction. Finally, we check the possibilities of
      managing of the immunosuppressive treatment and substitution of renal function by
      means of dialysis and/or simple or double transplant.

PMID- 20037626
TI  - Numerical representations are neither abstract nor automatic.
AB  - Here, I support and augment the argument put forth by Cohen Kadosh & Walsh (CK&W)
      that numerical representations are not abstract. I briefly review data that
      support the nonabstract nature of the representation of numbers between zero and
      one, and I discuss how a failure to test alternative hypotheses has led
      researchers to erroneously conclude that numerals automatically activate their
      semantic meaning.

PMID- 20037627
TI  - So you aspire to be a Professor?

PMID- 20037629
TI  - Design and synthesis of novel pinacolylboronate containing combretastatin
      'antimitotic agent' analogues.
AB  - We developed a procedure to synthesize pinacolyl boronate containing stilbene
      derivatives and used this procedure to synthesize boron-containing combretastatin
      analogues. The key step involves the Wittig reaction of the ylide 4-(4,4,5,5
      tetramethyl-1,3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide 11 with
      3,4,5-trimethoxy benzaldehyde in the presence of (t)BuONa in DMF, providing 88%
      yield. We are now in a position to evaluate the biological activity of these
      derivatives as modulators of TGF-beta signaling pathways.

PMID- 20037628
TI  - Phosphorylation of S776 and 14-3-3 binding modulate ataxin-1 interaction with
      splicing factors.
AB  - Ataxin-1 (Atx1), a member of the polyglutamine (polyQ) expanded protein family,
      is responsible for spinocerebellar ataxia type 1. Requirements for developing the
      disease are polyQ expansion, nuclear localization and phosphorylation of S776.
      Using a combination of bioinformatics, cell and structural biology approaches, we
      have identified a UHM ligand motif (ULM), present in proteins associated with
      splicing, in the C-terminus of Atx1 and shown that Atx1 interacts with and
      influences the function of the splicing factor U2AF65 via this motif. ULM
      comprises S776 of Atx1 and overlaps with a nuclear localization signal and a 14-3
      3 binding motif. We demonstrate that phosphorylation of S776 provides the
      molecular switch which discriminates between 14-3-3 and components of the
      spliceosome. We also show that an S776D Atx1 mutant previously designed to mimic
      phosphorylation is unsuitable for this aim because of the different chemical
      properties of the two groups. Our results indicate that Atx1 is part of a complex
      network of interactions with splicing factors and suggest that development of the
      pathology is the consequence of a competition of aggregation with native
      interactions. Studies of the interactions formed by non-expanded Atx1 thus
      provide valuable hints for understanding both the function of the non-pathologic
      protein and the causes of the disease.

PMID- 20037630
TI  - Dynamic fluctuations of protein-carbohydrate interactions promote protein
      aggregation.
AB  - Protein-carbohydrate interactions are important for glycoprotein structure and
      function. Antibodies of the IgG class, with increasing significance as
      therapeutics, are glycosylated at a conserved site in the constant Fc region. We
      hypothesized that disruption of protein-carbohydrate interactions in the
      glycosylated domain of antibodies leads to the exposure of aggregation-prone
      motifs. Aggregation is one of the main problems in protein-based therapeutics
      because of immunogenicity concerns and decreased efficacy. To explore the
      significance of intramolecular interactions between aromatic amino acids and
      carbohydrates in the IgG glycosylated domain, we utilized computer simulations,
      fluorescence analysis, and site-directed mutagenesis. We find that the surface
      exposure of one aromatic amino acid increases due to dynamic fluctuations.
      Moreover, protein-carbohydrate interactions decrease upon stress, while protein
      protein and carbohydrate-carbohydrate interactions increase. Substitution of the
      carbohydrate-interacting aromatic amino acids with non-aromatic residues leads to
      a significantly lower stability than wild type, and to compromised binding to Fc
      receptors. Our results support a mechanism for antibody aggregation via decreased
      protein-carbohydrate interactions, leading to the exposure of aggregation-prone
      regions, and to aggregation.

PMID- 20037633
TI  - How to Measure and Explain Achievement Change in Large-Scale Assessments: A
      Rejoinder.
AB  - In this rejoinder, we discuss substantive and methodological validity issues of
      large-scale assessments of trends in student achievement, commenting on the
      discussion paper by Van den Heuvel-Panhuizen, Robitzsch, Treffers, and Koller
      (2009). We focus on methodological challenges in deciding what to measure, how to
      measure it, and how to foster stability. Next, we discuss what to do with trends
      that are found. Finally, we reflect on how the research findings were received.

PMID- 20037632
TI  - Aging reveals a role for nigral tyrosine hydroxylase ser31 phosphorylation in
      locomotor activity generation.
AB  - BACKGROUND: Tyrosine hydroxylase (TH) regulates dopamine (DA) bioavailability.
      Its product, L-DOPA, is an established treatment for Parkinson's disease (PD),
      suggesting that TH regulation influences locomotion. Site-specific
      phosphorylation of TH at ser31 and ser40 regulates activity. No direct evidence
      shows that ser40 phosphorylation is the dominating mechanism of regulating TH
      activity in vivo, and physiologically-relevant stimuli increase L-DOPA
      biosynthesis independent of ser40 phosphorylation. Significant loss of locomotor
      activity occurs in aging as in PD, despite less loss of striatal DA or TH in
      aging compared to the loss associated with symptomatic PD. However, in the
      substantia nigra (SN), there is equivalent loss of DA or TH in aging and at the
      onset of PD symptoms. Growth factors increase locomotor activity in both PD and
      aging models and increase DA bioavailability and ser31 TH phosphorylation in SN,
      suggesting that ser31 TH phosphorylation status in the SN, not striatum,
      regulates DA bioavailability necessary for locomotor activity. METHODOLOGY AND
      PRINCIPAL FINDINGS: We longitudinally characterized locomotor activity in young
      and older Brown-Norway Fischer 344 F(1) hybrid rats (18 months apart in age) at
      two time periods, eight months apart. The aged group served as an intact and
      pharmacologically-naive source of deficient locomotor activity. Following
      locomotor testing, we analyzed DA tissue content, TH protein, and TH
      phosphorylation in striatum, SN, nucleus accumbens, and VTA. Levels of TH protein
      combined with ser31 phosphorylation alone reflected inherent differences in DA
      levels among the four regions. Measures strictly pertaining to locomotor activity
      initiation significantly correlated to DA content only in the SN. Nigral TH
      protein and ser31 phosphorylation together significantly correlated to test
      subject's maximum movement number, horizontal activity, and duration.
      CONCLUSIONS/SIGNIFICANCE: Together, these results show ser31 TH phosphorylation
      regulates DA bioavailability in intact neuropil, its status in the SN may
      regulate locomotor activity generation, and it may represent an accurate target
      for treating locomotor deficiency. They also show that neurotransmitter
      regulation in cell body regions can mediate behavioral outcomes and that ser31 TH
      phosphorylation plays a role in behaviors dependent upon catecholamines, such as
      dopamine.

PMID- 20037631
TI  - Reprogramming of 3' untranslated regions of mRNAs by alternative polyadenylation
      in generation of pluripotent stem cells from different cell types.
AB  - BACKGROUND: The 3' untranslated regions (3'UTRs) of mRNAs contain cis elements
      involved in post-transcriptional regulation of gene expression. Over half of all
      mammalian genes contain multiple polyadenylation sites that lead to different
      3'UTRs for a gene. Studies have shown that the alternative polyadenylation (APA)
      pattern varies across tissues, and is dynamically regulated in proliferating or
      differentiating cells. Generation of induced pluripotent stem (iPS) cells, in
      which differentiated cells are reprogrammed to an embryonic stem (ES) cell-like
      state, has been intensively studied in recent years. However, it is not known how
      3'UTRs are regulated during cell reprogramming. METHODS/MAIN FINDINGS: Using a
      computational method that robustly examines APA across DNA microarray data sets,
      we analyzed 3'UTR dynamics in generation of iPS cells from different cell types.
      We found that 3'UTRs shorten during reprogramming of somatic cells, the extent of
      which depends on the type of source cell. By contrast, reprogramming of
      spermatogonial cells involves 3'UTR lengthening. The alternative polyadenylation
      sites that are highly responsive to change of cell state in generation of iPS
      cells are also highly regulated during embryonic development in opposite
      directions. Compared with other sites, they are more conserved, can lead to
      longer alternative 3'UTRs, and are associated with more cis elements for
      polyadenylation. Consistently, reprogramming of somatic cells and germ cells
      involves significant upregulation and downregulation, respectively, of mRNAs
      encoding polyadenylation factors, and RNA processing is one of the most
      significantly regulated biological processes during cell reprogramming.
      Furthermore, genes containing target sites of ES cell-specific microRNAs (miRNAs)
      in different portions of 3'UTR are distinctively regulated during cell
      reprogramming, suggesting impact of APA on miRNA targeting.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these findings indicate that
      reprogramming of 3'UTRs by APA, which result from regulation of both general
      polyadenylation activity and cell type-specific factors and can reset post
      transcriptional gene regulatory programs in the cell, is an integral part of iPS
      cell generation, and the APA pattern can be a good biomarker for cell type and
      state, useful for sample classification. The results also suggest that
      perturbation of the mRNA polyadenylation machinery or RNA processing activity may
      facilitate generation of iPS cells.

PMID- 20037634
TI  - Ideal Point Discriminant Analysis Revisited with a Special Emphasis on
      Visualization.
AB  - Ideal point discriminant analysis is a classification tool which uses highly
      intuitive multidimensional scaling procedures. However, in the last paper, Takane
      wrote about it. He concludes that the interpretation is rather intricate and
      calls that a weakness of the model. We summarize the conditions that provide an
      easy interpretation and show that in maximum dimensionality they can be obtained
      without any loss. For reduced dimensionality, it is conjectured that loss is
      minor which is examined using several data sets.

PMID- 20037635
TI  - A Multivariate Multilevel Approach to the Modeling of Accuracy and Speed of Test
      Takers.
AB  - Response times on test items are easily collected in modern computerized testing.
      When collecting both (binary) responses and (continuous) response times on test
      items, it is possible to measure the accuracy and speed of test takers. To study
      the relationships between these two constructs, the model is extended with a
      multivariate multilevel regression structure which allows the incorporation of
      covariates to explain the variance in speed and accuracy between individuals and
      groups of test takers. A Bayesian approach with Markov chain Monte Carlo (MCMC)
      computation enables straightforward estimation of all model parameters. Model
      specific implementations of a Bayes factor (BF) and deviance information
      criterium (DIC) for model selection are proposed which are easily calculated as
      byproducts of the MCMC computation. Both results from simulation studies and real
      data examples are given to illustrate several novel analyses possible with this
      modeling framework.

PMID- 20037636
TI  - Solution Strategies and Achievement in Dutch Complex Arithmetic: Latent Variable
      Modeling of Change.
AB  - In the Netherlands, national assessments at the end of primary school (Grade 6)
      show a decline of achievement on problems of complex or written arithmetic over
      the last two decades. The present study aims at contributing to an explanation of
      the large achievement decrease on complex division, by investigating the
      strategies students used in solving the division problems in the two most recent
      assessments carried out in 1997 and in 2004. The students' strategies were
      classified into four categories. A data set resulted with two types of repeated
      observations within students: the nominal strategies and the dichotomous
      achievement scores (correct/incorrect) on the items administered.It is argued
      that latent variable modeling methodology is appropriate to analyze these data.
      First, latent class analyses with year of assessment as a covariate were carried
      out on the multivariate nominal strategy variables. Results showed a shift from
      application of the traditional long division algorithm in 1997, to the less
      accurate strategy of stating an answer without writing down any notes or
      calculations in 2004, especially for boys. Second, explanatory IRT analyses
      showed that the three main strategies were significantly less accurate in 2004
      than they were in 1997.

PMID- 20037637
TI  - Proteomic Profiling of Mesenchymal Stem Cell Responses to Mechanical Strain and
      TGF-beta1.
AB  - Mesenchymal stem cells (MSCs) are a potential source of smooth muscle cells
      (SMCs) for constructing tissue-engineered vascular grafts. However, the details
      of how specific combinations of vascular microenvironmental factors regulate MSCs
      are not well understood. Previous studies have suggested that both mechanical
      stimulation with uniaxial cyclic strain and chemical stimulation with
      transforming growth factor-beta1 (TGF-beta1) can induce smooth muscle markers in
      MSCs. In this study, we investigated the combined effects of uniaxial cyclic
      strain and TGF-beta1 stimulation on MSCs. By using a proteomic analysis, we found
      differential regulation of several proteins and genes, such as the up-regulation
      of TGF-beta1-induced protein ig-h3 (BGH3) protein levels by TGF-beta1 and up
      regulation of calponin 3 protein level by cyclic strain. At the gene expression
      level, BGH3 was induced by TGF-beta1, but calponin 3 was not significantly
      regulated by mechanical strain or TGF-beta1, which was in contrast to the
      synergistic up-regulation of calponin 1 gene expression by cyclic strain and TGF
      beta1. Further experiments with cycloheximide treatment suggested that the up
      regulation of calponin 3 by cyclic strain was at post-transcriptional level. The
      results in this study suggest that both mechanical stimulation and TGF-beta1
      signaling play unique and important roles in the regulation of MSCs at both
      transcriptional and post-transcriptional levels, and that a precise combination
      of microenvironmental cues may promote MSC differentiation.

PMID- 20037638
TI  - Reliability Beyond Theory and Into Practice.
AB  - The critical reactions of Bentler (2009, doi:10.1007/s11336-008-9100-1), Green
      and Yang (2009a, doi:10.1007/s11336-008-9098-4; 2009b, doi:10.1007/s11336-008
      9099-3), and Revelle and Zinbarg (2009, doi:10.1007/s11336-008-9102-z) to
      Sijtsma's (2009, doi:10.1007/s11336-008-9101-0) paper on Cronbach's alpha are
      addressed. The dissemination of psychometric knowledge among substantive
      researchers is discussed.

PMID- 20037639
TI  - On the Use, the Misuse, and the Very Limited Usefulness of Cronbach's Alpha.
AB  - This discussion paper argues that both the use of Cronbach's alpha as a
      reliability estimate and as a measure of internal consistency suffer from major
      problems. First, alpha always has a value, which cannot be equal to the test
      score's reliability given the interitem covariance matrix and the usual
      assumptions about measurement error. Second, in practice, alpha is used more
      often as a measure of the test's internal consistency than as an estimate of
      reliability. However, it can be shown easily that alpha is unrelated to the
      internal structure of the test. It is further discussed that statistics based on
      a single test administration do not convey much information about the accuracy of
      individuals' test performance. The paper ends with a list of conclusions about
      the usefulness of alpha.

PMID- 20037640
TI  - On the Non-Existence of Optimal Solutions and the Occurrence of "Degeneracy" in
      the CANDECOMP/PARAFAC Model.
AB  - The CANDECOMP/PARAFAC (CP) model decomposes a three-way array into a prespecified
      number of R factors and a residual array by minimizing the sum of squares of the
      latter. It is well known that an optimal solution for CP need not exist. We show
      that if an optimal CP solution does not exist, then any sequence of CP factors
      monotonically decreasing the CP criterion value to its infimum will exhibit the
      features of a so-called "degeneracy". That is, the parameter matrices become
      nearly rank deficient and the Euclidean norm of some factors tends to infinity.
      We also show that the CP criterion function does attain its infimum if one of the
      parameter matrices is constrained to be column-wise orthonormal.

PMID- 20037641
TI  - On Similarity Coefficients for 2x2 Tables and Correction for Chance.
AB  - This paper studies correction for chance in coefficients that are linear
      functions of the observed proportion of agreement. The paper unifies and extends
      various results on correction for chance in the literature. A specific class of
      coefficients is used to illustrate the results derived in this paper.
      Coefficients in this class, e.g. the simple matching coefficient and the
      Dice/Sorenson coefficient, become equivalent after correction for chance,
      irrespective of what expectation is used. The coefficients become either Cohen's
      kappa, Scott's pi, Mak's rho, Goodman and Kruskal's lambda, or Hamann's eta,
      depending on what expectation is considered appropriate. Both a multicategorical
      generalization and a multivariate generalization are discussed.

PMID- 20037642
TI  - Effect of the novel influenza A (H1N1) virus in the human immune system.
AB  - BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study
      any probable effects of that infection in the immune system of the host.
      METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of
      the presentation of signs of infection from 10 healthy volunteers; from 18 cases
      of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse
      RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were
      determined after staining with monoclonal antibodies and analysis by flow
      cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated from patients
      and stimulated with various bacterial stimuli. Concentrations of tumour necrosis
      factor-alpha, interleukin (IL)-1beta, IL-6, IL-18, interferon (FN)-alpha and of
      IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by
      H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong
      cytokine production after stimulation with most of bacterial stimuli. Defective
      cytokine responses were shown in response to stimulation with phytohemagglutin
      and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1
      infected patients were characterized by decreases of CD4-lymphocytes and of B
      lymphocytes and by increase of T-regulatory lymphocytes (Tregs).
      CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a
      characteristic impairment of the innate immune responses characterized by
      defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune
      responses are predominated by increase of Tregs. These findings signify a
      predisposition for pneumococcal infections after infection by H1N1 influenza.

PMID- 20037643
TI  - Interactions between age and ITN use determine the risk of febrile malaria in
      children.
AB  - BACKGROUND: Control measures which reduce individual exposure to malaria are
      expected to reduce disease, but also to eventually reduce immunity. Reassuringly,
      long term data following community wide ITN distribution show sustained benefits
      at a population level. However, the more common practice in Sub-Saharan Africa is
      to target ITN distribution on young children. There are few data on the long term
      outcomes of this practice. METHODOLOGY/PRINCIPAL FINDINGS: Episodes of febrile
      malaria were identified by active surveillance in 383 children over 18 months of
      follow up. In order to compare the short and long term outcomes of ITN use, we
      examined interactions between ITN use and age (12-42 months of age versus 42-80
      months) in determining the risk of febrile malaria. ITN use and older age
      protected against the first or only episode of malaria (Hazard Ratio [HR] = 0.33,
      95%CI 0.17-0.65 and HR = 0.30, 95%CI 0.17-0.51, respectively). The interaction
      term between ITN use and older age was HR = 2.91, 95%CI 1.02-8.3, p = 0.045,
      indicating that ITNs did not protect older children. When multiple episodes were
      included in analysis, ITN use and older age were again protective against malaria
      episodes (Incident Rate Ratio [IRR] = 0.43 95%CI 0.27-0.7) and IRR = 0.23, 95%CI
      0.13-0.42, respectively) and the interaction term indicated that ITNs did not
      protect older children (IRR = 2.71, 95%CI 1.3-5.7, p = 0.008).
      CONCLUSIONS/SIGNIFICANCE: These data on age interactions with ITN use suggest
      that larger scale studies on the long term individual outcomes should be
      undertaken if the policy of targeted ITN use for vulnerable groups is to
      continue.

PMID- 20037644
TI  - Quantitative PCR evaluation of cellular immune responses in Kenyan children
      vaccinated with a candidate malaria vaccine.
AB  - BACKGROUND: The T-cell mediated immune response plays a central role in the
      control of malaria after natural infection or vaccination. There is increasing
      evidence that T-cell responses are heterogeneous and that both the quality of the
      immune response and the balance between pro-inflammatory and regulatory T-cells
      determines the outcome of an infection. As Malaria parasites have been shown to
      induce immunosuppressive responses to the parasite and non-related antigens this
      study examined T-cell mediated pro-inflammatory and regulatory immune responses
      induced by malaria vaccination in children in an endemic area to determine if
      these responses were associated with vaccine immunogenicity. METHODS: Using real
      time RT- PCR we profiled the expression of a panel of key markers of
      immunogenecity at different time points after vaccination with two viral vector
      vaccines expressing the malaria TRAP antigen (FP9-TRAP and MVA-TRAP) or following
      rabies vaccination as a control. PRINCIPAL FINDINGS: The vaccine induced modest
      levels of IFN-gamma mRNA one week after vaccination. There was also an increase
      in FoxP3 mRNA expression in both TRAP stimulated and media stimulated cells in
      the FFM ME-TRAP vaccine group; however, this may have been driven by natural
      exposure to parasite rather than by vaccination. CONCLUSION: Quantitative PCR is
      a useful method for evaluating vaccine induced cell mediated immune responses in
      frozen PBMC from children in a malaria endemic country. Future studies should
      seek to use vaccine vectors that increase the magnitude and quality of the IFN
      gamma immune response in naturally exposed populations and should monitor the
      induction of a regulatory T cell response.

PMID- 20037645
TI  - Use of bacterially expressed dsRNA to downregulate Entamoeba histolytica gene
      expression.
AB  - BACKGROUND: Modern RNA interference (RNAi) methodologies using small interfering
      RNA (siRNA) oligonucleotide duplexes or episomally synthesized hairpin RNA are
      valuable tools for the analysis of gene function in the protozoan parasite
      Entamoeba histolytica. However, these approaches still require time-consuming
      procedures including transfection and drug selection, or costly synthetic
      molecules. PRINCIPAL FINDINGS: Here we report an efficient and handy alternative
      for E. histolytica gene down-regulation mediated by bacterial double-stranded RNA
      (dsRNA) targeting parasite genes. The Escherichia coli strain HT115 which is
      unable to degrade dsRNA, was genetically engineered to produce high quantities of
      long dsRNA segments targeting the genes that encode E. histolytica beta-tubulin
      and virulence factor KERP1. Trophozoites cultured in vitro were directly fed with
      dsRNA-expressing bacteria or soaked with purified dsRNA. Both dsRNA delivery
      methods resulted in significant reduction of protein expression. In vitro host
      cell-parasite assays showed that efficient downregulation of kerp1 gene
      expression mediated by bacterial dsRNA resulted in significant reduction of
      parasite adhesion and lytic capabilities, thus supporting a major role for KERP1
      in the pathogenic process. Furthermore, treatment of trophozoites cultured in
      microtiter plates, with a repertoire of eighty-five distinct bacterial dsRNA
      segments targeting E. histolytica genes with unknown function, led to the
      identification of three genes potentially involved in the growth of the parasite.
      CONCLUSIONS: Our results showed that the use of bacterial dsRNA is a powerful
      method for the study of gene function in E. histolytica. This dsRNA delivery
      method is also technically suitable for the study of a large number of genes,
      thus opening interesting perspectives for the identification of novel drug and
      vaccine targets.

PMID- 20037646
TI  - 17beta-estradiol enhances the response of plasmacytoid dendritic cell to CpG.
AB  - Gender differences in immune capabilities suggest that sex hormones such as
      estrogens were involved in the regulation of the immunocompetence. Numerous
      studies also suggest that plasmacytoid dendritic cells (PDCs) play a pathogenic
      role in SLE. However, it is unclear whether estrogen can modulate the function of
      PDCs to influence the development of SLE. In the present study, PDCs from murine
      spleens were treated with 17beta-estradiol (E2) and CpG respectively or both in
      vitro, then cell viability, costimulatory molecule expression, cytokine secretion
      of PDCs, as well as stimulatory capacity of PDCs to B cells were analyzed.
      Results showed that E2 and CpG increased the cell viability and costimulatory
      molecule expression on PDCs synergistically. Moreover, the intracellular and
      extracellular secretion of IFN-alpha was increased by E2 or E2 plus CpG. In
      addition, E2 and CpG also increased the stimulatory capacity of PDCs to B cells,
      and the viability of B cells was decreased after neutralizing IFN-alpha
      significantly. In the experiments in vivo, mice received daily s.c. injections of
      E2 and CpG respectively or both, then we found that the plasma concentration of
      IgM were elevated by E2 and CpG synergistically and the expression of IFN
      alpha/beta in spleens were noticeably increased by CpG plus E2 compared with the
      treatment of E2 or CpG only. This study indicates that E2 could exacerbate PDCs'
      activation with CpG, which further activates B cells to upregulate susceptibility
      to autoantigens. IFN-alpha plays an important role in the stimulatory effect of
      PDCs on B cells. E2 stimulation of IFN-alpha production may result in female
      prevalence in autoimmune diseases such as SLE through activation of PDCs. This
      study provides novel evidence of relationship between estrogen and SLE and also
      sheds light on gender biases among SLE patients.

PMID- 20037647
TI  - High throughput sequencing and proteomics to identify immunogenic proteins of a
      new pathogen: the dirty genome approach.
AB  - BACKGROUND: With the availability of new generation sequencing technologies,
      bacterial genome projects have undergone a major boost. Still, chromosome
      completion needs a costly and time-consuming gap closure, especially when
      containing highly repetitive elements. However, incomplete genome data may be
      sufficiently informative to derive the pursued information. For emerging
      pathogens, i.e. newly identified pathogens, lack of release of genome data during
      gap closure stage is clearly medically counterproductive. METHODS/PRINCIPAL
      FINDINGS: We thus investigated the feasibility of a dirty genome approach, i.e.
      the release of unfinished genome sequences to develop serological diagnostic
      tools. We showed that almost the whole genome sequence of the emerging pathogen
      Parachlamydia acanthamoebae was retrieved even with relatively short reads from
      Genome Sequencer 20 and Solexa. The bacterial proteome was analyzed to select
      immunogenic proteins, which were then expressed and used to elaborate the first
      steps of an ELISA. CONCLUSIONS/SIGNIFICANCE: This work constitutes the proof of
      principle for a dirty genome approach, i.e. the use of unfinished genome
      sequences of pathogenic bacteria, coupled with proteomics to rapidly identify new
      immunogenic proteins useful to develop in the future specific diagnostic tests
      such as ELISA, immunohistochemistry and direct antigen detection. Although
      applied here to an emerging pathogen, this combined dirty genome
      sequencing/proteomic approach may be used for any pathogen for which better
      diagnostics are needed. These genome sequences may also be very useful to develop
      DNA based diagnostic tests. All these diagnostic tools will allow further
      evaluations of the pathogenic potential of this obligate intracellular bacterium.

PMID- 20037648
TI  - Isoform-specific contributions of alpha-actinin to glioma cell mechanobiology.
AB  - Glioblastoma Multiforme (GBM) is a malignant astrocytic tumor associated with low
      survival rates because of aggressive infiltration of tumor cells into the brain
      parenchyma. Expression of the actin binding protein alpha-actinin has been
      strongly correlated with the invasive phenotype of GBM in vivo. To probe the
      cellular basis of this correlation, we have suppressed expression of the
      nonmuscle isoforms alpha-actinin-1 and alpha-actinin-4 and examined the
      contribution of each isoform to the structure, mechanics, and motility of human
      glioma tumor cells in culture. While subcellular localization of each isoform is
      distinct, suppression of either isoform yields a phenotype that includes
      dramatically reduced motility, compensatory upregulation and redistribution of
      vinculin, reduced cortical elasticity, and reduced ability to adapt to changes in
      the elasticity of the extracellular matrix (ECM). Mechanistic studies reveal a
      relationship between alpha-actinin and non-muscle myosin II in which depletion of
      either alpha-actinin isoform reduces myosin expression and maximal cell-ECM
      tractional forces. Our results demonstrate that both alpha-actinin-1 and alpha
      actinin-4 make critical and distinct contributions to cytoskeletal organization,
      rigidity-sensing, and motility of glioma cells, thereby yielding mechanistic
      insight into the observed correlation between alpha-actinin expression and GBM
      invasiveness in vivo.

PMID- 20037649
TI  - Pseudomonas aeruginosa exploits lipid A and muropeptides modification as a
      strategy to lower innate immunity during cystic fibrosis lung infection.
AB  - Pseudomonas aeruginosa can establish life-long airways chronic infection in
      patients with cystic fibrosis (CF) with pathogenic variants distinguished from
      initially acquired strain. Here, we analysed chemical and biological activity of
      P. aeruginosa Pathogen-Associated Molecular Patterns (PAMPs) in clonal strains,
      including mucoid and non-mucoid phenotypes, isolated during a period of up to 7.5
      years from a CF patient. Chemical structure by MS spectrometry defined
      lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with
      specific structural modifications temporally associated with CF lung infection.
      Gene sequence analysis revealed novel mutation in pagL, which supported lipid A
      changes. Both LPS and PGN had different potencies when activating host innate
      immunity via binding TLR4 and Nod1. Significantly higher NF-kB activation, IL-8
      expression and production were detected in HEK293hTLR4/MD2-CD14 and HEK293hNod1
      after stimulation with LPS and PGN respectively, purified from early P.
      aeruginosa strain as compared to late strains. Similar results were obtained in
      macrophages-like cells THP-1, epithelial cells of CF origin IB3-1 and their
      isogenic cells C38, corrected by insertion of cystic fibrosis transmembrane
      conductance regulator (CFTR). In murine model, altered LPS structure of P.
      aeruginosa late strains induces lower leukocyte recruitment in bronchoalveolar
      lavage and MIP-2, KC and IL-1beta cytokine levels in lung homogenates when
      compared with early strain. Histopathological analysis of lung tissue sections
      confirmed differences between LPS from early and late P. aeruginosa. Finally, in
      this study for the first time we unveil how P. aeruginosa has evolved the
      capacity to evade immune system detection, thus promoting survival and
      establishing favourable conditions for chronic persistence. Our findings provide
      relevant information with respect to chronic infections in CF.

PMID- 20037650
TI  - Glucose metabolism, islet architecture, and genetic homogeneity in imprinting of
      [Ca2+](i) and insulin rhythms in mouse islets.
AB  - We reported previously that islets isolated from individual, outbred Swiss
      Webster mice displayed oscillations in intracellular calcium ([Ca2+](i)) that
      varied little between islets of a single mouse but considerably between mice, a
      phenomenon we termed "islet imprinting." We have now confirmed and extended these
      findings in several respects. First, imprinting occurs in both inbred (C57BL/6J)
      as well as outbred mouse strains (Swiss-Webster; CD1). Second, imprinting was
      observed in NAD(P)H oscillations, indicating a metabolic component. Further,
      short-term exposure to a glucose-free solution, which transiently silenced
      [Ca2+](i) oscillations, reset the oscillatory patterns to a higher frequency.
      This suggests a key role for glucose metabolism in maintaining imprinting, as
      transiently suppressing the oscillations with diazoxide, a K(ATP)-channel opener
      that blocks [Ca2+](i) influx downstream of glucose metabolism, did not change the
      imprinted patterns. Third, imprinting was not as readily observed at the level of
      single beta cells, as the [Ca2+](i) oscillations of single cells isolated from
      imprinted islets exhibited highly variable, and typically slower [Ca2+](i)
      oscillations. Lastly, to test whether the imprinted [Ca2+](i) patterns were of
      functional significance, a novel microchip platform was used to monitor insulin
      release from multiple islets in real time. Insulin release patterns correlated
      closely with [Ca2+](i) oscillations and showed significant mouse-to-mouse
      differences, indicating imprinting. These results indicate that islet imprinting
      is a general feature of islets and is likely to be of physiological significance.
      While islet imprinting did not depend on the genetic background of the mice,
      glucose metabolism and intact islet architecture may be important for the
      imprinting phenomenon.

PMID- 20037652
TI  - Multiple Unfolding Intermediates Obtained by Molecular Dynamic Simulations under
      Stretching for Immunoglobulin-Binding Domain of Protein G.
AB  - We have studied the mechanical properties of the immunoglobulin-binding domain of
      protein G at the atomic level under stretching at constant velocity using
      molecular dynamics simulations. We have found that the unfolding process can
      occur either in a single step or through intermediate states. Analysis of the
      trajectories from the molecular dynamic simulations showed that the mechanical
      unfolding of the immunoglobulin-binding domain of protein G is triggered by the
      separation of the terminal beta-strands and the order in which the secondary
      structure elements break is practically the same in two- and multi-state events
      and at the different extension velocities studied. It is seen from our analysis
      of 24 trajectories that the theoretical pathway of mechanical unfolding for the
      immunoglobulin-binding domain of protein G does not coincide with that proposed
      in denaturant studies in the absence of force.

PMID- 20037651
TI  - Intraclonal protein expression heterogeneity in recombinant CHO cells.
AB  - Therapeutic glycoproteins have played a major role in the commercial success of
      biotechnology in the post-genomic era. But isolating recombinant mammalian cell
      lines for large-scale production remains costly and time-consuming, due to
      substantial variation and unpredictable stability of expression amongst
      transfected cells, requiring extensive clone screening to identify suitable high
      producers. Streamlining this process is of considerable interest to industry yet
      the underlying phenomena are still not well understood. Here we examine an
      antibody-expressing Chinese hamster ovary (CHO) clone at single-cell resolution
      using flow cytometry and vectors, which couple light and heavy chain
      transcription to fluorescent markers. Expression variation has traditionally been
      attributed to genetic heterogeneity arising from random genomic integration of
      vector DNA. It follows that single cell cloning should yield a homogeneous cell
      population. We show, in fact, that expression in a clone can be surprisingly
      heterogeneous (standard deviation 50 to 70% of the mean), approaching the level
      of variation in mixed transfectant pools, and each antibody chain varies in
      tandem. Phenotypic variation is fully developed within just 18 days of cloning,
      yet is not entirely explained by measurement noise, cell size, or the cell cycle.
      By monitoring the dynamic response of subpopulations and subclones, we show that
      cells also undergo slow stochastic fluctuations in expression (half-life 2 to 11
      generations). Non-genetic diversity may therefore play a greater role in clonal
      variation than previously thought. This also has unexpected implications for
      expression stability. Stochastic gene expression noise and selection bias lead to
      perturbations from steady state at the time of cloning. The resulting transient
      response as clones reestablish their expression distribution is not ordinarily
      accounted for but can contribute to declines in median expression over timescales
      of up to 50 days. Noise minimization may therefore be a novel strategy to reduce
      apparent expression instability and simplify cell line selection.

PMID- 20037653
TI  - Evolution of primary hemostasis in early vertebrates.
AB  - Hemostasis is a defense mechanism which protects the organism in the event of
      injury to stop bleeding. Recently, we established that all the known major
      mammalian hemostatic factors are conserved in early vertebrates. However, since
      their highly vascularized gills experience high blood pressure and are exposed to
      the environment, even very small injuries could be fatal to fish. Since trypsins
      are forerunners for coagulation proteases and are expressed by many
      extrapancreatic cells such as endothelial cells and epithelial cells, we
      hypothesized that trypsin or trypsin-like proteases from gill epithelial cells
      may protect these animals from gill bleeding following injuries. In this paper we
      identified the release of three different trypsins from fish gills into water
      under stress or injury, which have tenfold greater serine protease activity
      compared to bovine trypsin. We found that these trypsins activate the
      thrombocytes and protect the fish from gill bleeding. We found 27 protease
      activated receptors (PARs) by analyzing zebrafish genome and classified them into
      five groups, based on tethering peptides, and two families, PAR1 and PAR2, based
      on homologies. We also found a canonical member of PAR2 family, PAR2-21A which is
      activated more readily by trypsin, and PAR2-21A tethering peptide stops gill
      bleeding just as trypsin. This finding provides evidence that trypsin cleaves a
      PAR2 member on thrombocyte surface. In conclusion, we believe that the gills are
      evolutionarily selected to produce trypsin to activate PAR2 on thrombocyte
      surface and protect the gills from bleeding. We also speculate that trypsin may
      also protect the fish from bleeding from other body injuries due to quick contact
      with the thrombocytes. Thus, this finding provides evidence for the role of
      trypsins in primary hemostasis in early vertebrates.

PMID- 20037655
TI  - Generation of myocardial wall surface meshes from segmented MRI.
AB  - This paper presents a novel method for the generation of myocardial wall surface
      meshes from segmented 3D MR images, which typically have strongly anisotropic
      voxels. The method maps a premeshed sphere to the surface of the segmented
      object. The mapping is defined by the gradient field of the solution of the
      Laplace equation between the sphere and the surface of the object. The same
      algorithm is independently used to generate the surface meshes of the epicardium
      and endocardium of the four cardiac chambers. The generated meshes are smooth
      despite the strong voxel anisotropy, which is not the case for the marching cubes
      and related methods. While the proposed method generates more regular mesh
      triangles than the marching cubes and allows for a complete control of the number
      of triangles, the generated meshes are still close to the ones obtained by the
      marching cubes. The method was tested on 3D short-axis cardiac MR images with
      strongly anisotropic voxels in the long-axis direction. For the five tested
      subjects, the average in-slice distance between the meshes generated by the
      proposed method and by the marching cubes was 0.4 mm.

PMID- 20037654
TI  - Telomere length in human adults and high level natural background radiation.
AB  - BACKGROUND: Telomere length is considered as a biomarker of aging, stress,
      cancer. It has been associated with many chronic diseases such as hypertension
      and diabetes. Although, telomere shortening due to ionizing radiation has been
      reported in vitro, no in vivo data is available on natural background radiation
      and its effect on telomere length. METHODOLOGY/PRINCIPAL FINDINGS: The present
      investigation is an attempt to determine the telomere length among human adults
      residing in high level natural radiation areas (HLNRA) and the adjacent normal
      level radiation areas (NLNRA) of Kerala coast in Southwest India. Genomic DNA was
      isolated from the peripheral blood mononuclear cells of 310 individuals (HLNRA: N
      = 233 and NLNRA: N = 77). Telomere length was determined using real time q-PCR.
      Both telomere (T) and single copy gene (S) specific primers were used to
      calculate the relative T/S and expressed as the relative telomere length. The
      telomere length was determined to be 1.22+/-0.15, 1.12+/-0.15, 1.08+/-0.08,
      1.12+/-0.11, respectively, among the four dose groups (</=1.50, 1.51-3.00, 3.01
      5.00 and >5.00 mGy per year), which did not show any dose response. The results
      suggested that the high level natural chronic radiation did not have significant
      effect on telomere length among young adult population living in HLNRA, which is
      indicative of better repair of telomeric ends. No significant difference in
      telomere length was observed between male and female individuals. In the present
      investigation, although the determination of telomere length was studied among
      the adults with an age group between 18 to 40 years (mean maternal age: 26.10+/
      4.49), a negative correlation was observed with respect to age. However, inter
      individual variation was (0.81-1.68) was clearly observed.
      CONCLUSIONS/SIGNIFICANCE: In this preliminary investigation, we conclude that
      elevated level of natural background radiation has no significant effect on
      telomere length among the adult population residing in HLNRAs of Kerala coast. To
      our knowledge, this is the first report from HLNRAs of the world where telomere
      length was determined on human adults. However, more samples from each background
      dose group and samples from older population need to be studied to derive firm
      conclusions.

PMID- 20037656
TI  - PROC QTL-A SAS Procedure for Mapping Quantitative Trait Loci.
AB  - Statistical analysis system (SAS) is the most comprehensive statistical analysis
      software package in the world. It offers data analysis for almost all experiments
      under various statistical models. Each analysis is performed using a particular
      subroutine, called a procedure (PROC). For example, PROC ANOVA performs analysis
      of variances. PROC QTL is a user-defined SAS procedure for mapping quantitative
      trait loci (QTL). It allows users to perform QTL mapping for continuous and
      discrete traits within the SAS platform. Users of PROC QTL are able to take
      advantage of all existing features offered by the general SAS software, for
      example, data management and graphical treatment. The current version of PROC QTL
      can perform QTL mapping for all line crossing experiments using maximum
      likelihood (ML), least square (LS), iteratively reweighted least square (IRLS),
      Fisher scoring (FISHER), Bayesian (BAYES), and empirical Bayes (EBAYES) methods.

PMID- 20037657
TI  - Unique Properties of Thermally Tailored Copper: Magnetically Active Regions and
      Anomalous X-ray Fluorescence Emissions.
AB  - When high-purity copper (>/=99.98%(wt)) is melted, held in its liquid state for a
      few hours with iterative thermal cycling, then allowed to resolidify, the ingot
      surface is found to have many small regions that are magnetically active. X-ray
      fluorescence analysis of these regions exhibit remarkably intense lines from
      "sensitized elements" (SE), including in part or fully the contiguous series V,
      Cr, Mn, Fe, and Co. The XRF emissions from SE are far more intense than expected
      from known impurity levels. Comparison with blanks and standards show that the
      thermal "tailoring" also introduces strongly enhanced SE emissions in samples
      taken from the interior of the copper ingots. For some magnetic regions, the
      location as well as the SE emissions, although persistent, vary irregularly with
      time. Also, for some regions extraordinarily intense "sensitized iron" (SFe)
      emissions occur, accompanied by drastic attenuation of Cu emissions.

PMID- 20037658
TI  - Pharmacological Characterization of Inositol 1,4,5-tris Phosphate Receptors in
      Human Platelet Membranes.
AB  - The phosphatidylinositol (PI) hydrolysis signaling system has been shown to be
      altered in platelets of depressed and schizophrenic subjects. Inositol (1,4,5)
      trisphosphate (Ins(1,4,5)P(3)), an integral component of the PI signaling system,
      mobilizes Ca(2+) by activating Ins(1,4,5)P(3) receptors. To eventually
      investigate the role of Ins(1,4,5)P(3) receptors in depression and other mental
      disorders, we characterized [(3)H]Ins(1,4,5)P(3) binding sites in crude platelet
      membranes prepared from small amounts of blood obtained from healthy human
      control subjects. We found a single, saturable binding site for
      [(3)H]Ins(1,4,5)P(3) to crude platelet membranes, which is time dependent and
      modulated by pH, inositol phosphates, and heparin. Since cyclic adenosine
      monophosphate (cAMP) and Ca(2+) have been shown to be important modulators in
      Ins(1,4,5)P(3) receptors, in the present study we also determined the effects of
      various concentrations of CaCI(2) and forskolin on Ins(1,4,5)P(3) binding to
      platelet membranes. CaCI(2) modulated [(3)H]Ins(1,4,5)P(3) binding sites in a
      biphasic manner: at lower concentrations it inhibited [(3)H]Ins(1,4,5)P(3)
      binding, whereas at higher concentrations, it stimulated [(3)H]Ins(1,4,5)P(3)
      binding. On the other hand, forskolin inhibited [(3)H]Ins(1,4,5)P(3) binding. Our
      results thus suggest that the pharmacological characteristics of
      [(3)H]Ins(1,4,5)P(3) binding to crude platelet membranes are similar to that of
      Ins(1,4,5)P(3) receptors; and that both Ca(2+) and cAMP modulate
      [(3)H]Ins(1,4,5)P(3) binding in crude platelet membranes.

PMID- 20037659
TI  - Parent Depression and Child Anxiety: An Overview of the Literature with Clinical
      Implications.
AB  - The association of parental depression with child anxiety has received relatively
      little attention in the literature. In this paper we initially present several
      reasons for examining this relationship. We then summarize the empirical support
      for a link between these two variables. Finally, we discuss directions for future
      research and clinical implications of an association of parental depression with
      child anxiety.

PMID- 20037660
TI  - Explaining The Current Role Of High Frequency Ultrasound In Ophthalmic Diagnosis
      (Ophthalmic Ultrasound).
AB  - Ultrasound has become as indispensable as indirect ophthalmoscopy or slit lamp in
      evaluation of the eye. It is an important adjuvant for the clinical assessment of
      a variety of ocular and orbital diseases. Advances in instrumentation, higher
      frequencies and more sensitivity and resolution have resulted in continuous
      improvement in image quality.Very high frequency ultrasound uses frequencies in
      the range of 35 to 100 MHz to show greater detail of the anterior segment.
      Penetration is limited for these higher frequencies to only a few millimeters and
      thus only the anterior vitreous behind the ciliary body and lens can be imaged.
      High frequency ultrasound in the range of 20 to 30 MHz has a penetration of about
      10 mm and can be used for posterior pole evaluation of the retina and choroid.

PMID- 20037661
TI  - Targeting acidic diseased tissue: New technology based on use of the pH (Low)
      Insertion Peptide (pHLIP).
AB  - We discuss a peptide that targets cells in the acidic tissues that result from a
      range of pathological states, including tumours, and that can also translocate
      cell-impermeable cargo molecules across cell membranes in a pH-dependent manner.
      The technology is based on the interactions of a water-soluble membrane peptide,
      which we call pHLIP (pH (Low) Insertion Peptide), with the lipid bilayers of cell
      membranes. at the normal pH of healthy tissue it binds to cell surfaces, but at
      low pH pHLIP inserts as a monomer across the cell membrane to form a stable
      transmembrane helix. pHLIP holds promise for imaging and drug delivery
      applications.

PMID- 20037663
TI  - Confidence Intervals of Interaction Index for Assessing Multiple Drug
      Interaction.
AB  - Studies of interactions among biologically active agents have become increasingly
      important in many branches of biomedical research. We consider that the Loewe
      additivity model is one of the best general reference models for defining drug
      interactions. Based on the Loewe additivity model, synergy occurs when the
      interaction index is less than one, and antagonism occurs when interaction index
      is greater than one. Starting from the Loewe additivity model and the marginal
      dose-effect curve for each drug involved in a combination, we first present a
      procedure to estimate the interaction index and its associated confidence
      interval at a combination dose with observed effects. Following Chou and
      Talalay's method for assessing drug interaction based on the plot of interaction
      indices versus effects for combination doses at a fixed ray, we then construct a
      pointwise (1-alpha)x100% confidence bound for the curve of interaction indices
      versus effects. We found that these methods work better on the logarithm
      transformed scale than on the untransformed scale of the interaction index. We
      provide simulations and case studies to illustrate the performances of these two
      procedures, and present their pros and cons. We also provide S-Plus/R code to
      facilitate the implementation of these two procedures.

PMID- 20037662
TI  - Transforming Dissatisfaction with Services into Self-Determination: A Social
      Psychological Perspective on Community Program Effectiveness.
AB  - A field study of supported employment for adults with mental illness (N=174)
      provided an experimental test of cognitive dissonance theory. We predicted that
      most work-interested individuals randomly assigned to a non-preferred program
      would reject services and lower their work aspirations. However, individuals who
      chose to pursue employment through a non-preferred program were expected to
      resolve this dissonance through favorable service evaluations and strong efforts
      to succeed at work. Significant work interest-by-service preference interactions
      supported these predictions. Over two years, participants interested in
      employment who obtained work through a non-preferred program stayed employed a
      median of 362 days versus 108 days for those assigned to a preferred program, and
      participants who obtained work through a non-preferred program had higher service
      satisfaction.

PMID- 20037664
TI  - Application of Biostatistics and Bioinformatics Tools to Identify Putative
      Transcription Factor-Gene Regulatory Network of Ankylosing Spondylitis and
      Sarcoidosis.
AB  - Transcription factors and corresponding cis-regulatory elements are considered
      key components in gene regulation. We combined biostatistics and bioinformatics
      tools to streamline identification of putative transcription factor-gene
      regulatory networks unique for two immune-mediated diseases, ankylosing
      spondylitis and sarcoidosis. After identifying differentially expressed genes
      from microarrays, we employed tightCluster to find tight clusters of potentially
      co-regulated genes. By subsequently applying bioinformatics tools to search for
      common cis-regulatory elements, putative transcription factor-gene regulatory
      networks were found. Recognition of these networks by applying this methodology
      could pave the way for new insights into disease pathogenesis.

PMID- 20037665
TI  - Emotional awareness, gender, and suspiciousness.
AB  - We investigated the causal relation between emotional awareness (EA) and
      suspiciousness, and whether this relation is moderated by gender. After inducing
      an unpleasant mood, we manipulated EA by having participants read one of two
      versions of a story (the high EA condition provided cues to what the participant
      was feeling and why, whereas the low EA condition did not). Following the
      manipulation, one sample of participants completed a measure of suspiciousness,
      and a second, independent sample of participants described their emotional state.
      Emotional Awareness Condition x Gender effects were obtained for suspiciousness
      and EA. Men in the low EA condition reported significantly higher levels of
      suspiciousness and lower levels of EA than men in the high EA condition. Women in
      both conditions reported equally high levels of EA, which were greater than those
      of men in both conditions, and the manipulation did not affect their levels of
      suspiciousness.

PMID- 20037666
TI  - The Impact of Community Violence Exposure on Anxiety in Children of Mothers with
      Depression.
AB  - The dual risk of exposure to community violence and maternal depression has
      potentially negative effects on children. This study examined whether social
      skills served as a protective factor for the impact of community violence
      exposure on anxiety within children of African American mothers with depression.
      Multiple regressions showed that community violence exposure was associated with
      less anxious coping but more physical symptoms. Findings support that younger
      children who view themselves as being socially skilled also exhibit higher levels
      of anxious coping. Implications addressing the importance of age, physical
      symptoms of anxiety, and anxious vigilance for interventions are discussed.

PMID- 20037667
TI  - INVESTIGATING THE LONGITUDINAL RELATION BETWEEN OFFENDING FREQUENCY AND OFFENDING
      VARIETY.
AB  - Researchers interested in longitudinal patterns of criminal offending have paid
      close attention to several dimensions of criminal careers. Although it might be
      expected that several dimensions are strongly linked to one another, research has
      not explored their joint distribution. The study uses trajectory-based
      methodology to examine the joint relation between offending variety and offending
      frequency in a large sample of serious offenders from adolescence to early
      adulthood and also tests how several risk factors relate to the joint covariation
      between variety and frequency. Results indicate strong concordance between low
      and high rate variety and frequency trajectories but a more modest concordance
      among moderate rate variety and frequency trajectories. Criminal history,
      individual, parent, and peer characteristics predict differences in concordance
      between variety and frequency trajectories. Theoretical implications and
      directions for further research are outlined.

PMID- 20037668
TI  - Impulsivity in Animal Models for Drug Abuse Disorders.
AB  - Different conceptual frameworks have been generated to explain substance abuse;
      of relevance to this article, dysfunction of impulse control systems that are
      required for avoiding or stopping drug-seeking and -taking may play a key role in
      addiction. This review summarizes work in animal models that explains the
      pervasive association between impulse control and substance abuse. It further
      underscores the concept that impulse control may be a critical target for
      pharmacological intervention in the treatment of addictions and suggests that
      further developments in animal models for impulsivity may be useful in expanding
      our understanding and treatment of drug abuse.

PMID- 20037669
TI  - The Sunk-Time Effect: An Exploration.
AB  - We explored the potential for a sunk-cost effect in the realm of time.
      Questionnaire studies (Experiments 1-4) obtained a sunk-time effect that was
      robust to manipulations of prospective value, individual versus group
      consequences, and the effort or enjoyment inherent in the time. Behavioral
      experiments (Experiments 5-7) also suggested a sunk-time effect and found support
      for a personal responsibility by sunk cost interaction on choice behavior. We
      discuss theoretical implications and a potential connection to animal sunk cost
      phenomena.

PMID- 20037670
TI  - Coarse coding and discourse comprehension in adults with right hemisphere brain
      damage.
AB  - BACKGROUND: Various investigators suggest that some discourse-level comprehension
      difficulties in adults with right hemisphere brain damage (RHD) have a lexical
      semantic basis. As words are processed, the intact right hemisphere arouses and
      sustains activation of a wide-ranging network of secondary or peripheral meanings
      and features-a phenomenon dubbed "coarse coding". Coarse coding impairment has
      been postulated to underpin some prototypical RHD comprehension deficits, such as
      difficulties with nonliteral language interpretation, discourse integration, some
      kinds of inference generation, and recovery when a reinterpretation is needed. To
      date, however, no studies have addressed the hypothesised link between coarse
      coding deficit and discourse comprehension in RHD.  AIMS: The current
      investigation examined whether coarse coding was related to performance on two
      measures of narrative comprehension in adults with RHD.  METHODS
      #ENTITYSTARTX00026; PROCEDURES: Participants were 32 adults with unilateral RHD
      from cerebrovascular accident, and 38 adults without brain damage. Coarse coding
      was operationalised as poor activation of peripheral/weakly related semantic
      features of words. For the coarse coding assessment, participants listened to
      spoken sentences that ended in a concrete noun. Each sentence was followed by a
      spoken target phoneme string. Targets were subordinate semantic features of the
      sentence-final nouns that were incompatible with their dominant mental
      representations (e.g., "rotten" for apple). Targets were presented at two post
      noun intervals. A lexical decision task was used to gauge both early activation
      and maintenance of activation of these weakly related semantic features. One of
      the narrative tasks assessed comprehension of implied main ideas and details,
      while the other indexed high-level inferencing and integration. Both
      comprehension tasks were presented auditorily. For all tasks, accuracy of
      performance was the dependent measure. Correlations were computed within the RHD
      group between both the early and late coarse coding measures and the two
      discourse measures. Additionally, ANCOVA and independent t-tests were used to
      compare both early and sustained coarse coding in subgroups of good and poor RHD
      comprehenders.  OUTCOMES #ENTITYSTARTX00026; RESULTS: The group with RHD was less
      accurate than the control group on all measures. The finding of coarse coding
      impairment (difficulty activating/sustaining activation of a word's peripheral
      features) may appear to contradict prior evidence of RHD suppression deficit
      (prolonged activation for context-inappropriate meanings of words). However, the
      sentence contexts in this study were unbiased and thus did not provide an
      appropriate test of suppression function. Correlations between coarse coding and
      the discourse measures were small and nonsignificant. There were no differences
      in coarse coding between RHD comprehension subgroups on the high-level
      inferencing task. There was also no distinction in early coarse coding for
      subgroups based on comprehension of implied main ideas and details. But for these
      same subgroups, there was a difference in sustained coarse coding. Poorer RHD
      comprehenders of implied information from discourse were also poorer at
      maintaining activation for semantically distant features of concrete nouns. 
      CONCLUSIONS: This study provides evidence of a variant of the postulated link
      between coarse coding and discourse comprehension in RHD. Specifically, adults
      with RHD who were particularly poor at sustaining activation for peripheral
      semantic features of nouns were also relatively poor comprehenders of implied
      information from narratives.

PMID- 20037671
TI  - Designing Tracking Software for Image-Guided Surgery Applications: IGSTK
      Experience.
AB  - OBJECTIVE: Many image-guided surgery applications require tracking devices as
      part of their core functionality. The Image-Guided Surgery Toolkit (IGSTK) was
      designed and developed to interface tracking devices with software applications
      incorporating medical images. METHODS: IGSTK was designed as an open source C++
      library that provides the basic components needed for fast prototyping and
      development of image-guided surgery applications. This library follows a
      component-based architecture with several components designed for specific sets
      of image-guided surgery functions. At the core of the toolkit is the tracker
      component that handles communication between a control computer and navigation
      device to gather pose measurements of surgical instruments present in the
      surgical scene. The representations of the tracked instruments are superimposed
      on anatomical images to provide visual feedback to the clinician during surgical
      procedures. RESULTS: The initial version of the IGSTK toolkit has been released
      in the public domain and several trackers are supported. The toolkit and related
      information are available at www.igstk.org. CONCLUSION: With the increased
      popularity of minimally invasive procedures in health care, several tracking
      devices have been developed for medical applications. Designing and implementing
      high-quality and safe software to handle these different types of trackers in a
      common framework is a challenging task. It requires establishing key software
      design principles that emphasize abstraction, extensibility, reusability, fault
      tolerance, and portability. IGSTK is an open source library that satisfies these
      needs for the image-guided surgery community.

PMID- 20037673
TI  - A group bridge approach for variable selection.
AB  - In multiple regression problems when covariates can be naturally grouped, it is
      important to carry out feature selection at the group and within-group individual
      variable levels simultaneously. The existing methods, including the lasso and
      group lasso, are designed for either variable selection or group selection, but
      not for both. We propose a group bridge approach that is capable of simultaneous
      selection at both the group and within-group individual variable levels. The
      proposed approach is a penalized regularization method that uses a specially
      designed group bridge penalty. It has the oracle group selection property, in
      that it can correctly select important groups with probability converging to one.
      In contrast, the group lasso and group least angle regression methods in general
      do not possess such an oracle property in group selection. Simulation studies
      indicate that the group bridge has superior performance in group and individual
      variable selection relative to several existing methods.

PMID- 20037672
TI  - Electronic Diaries: Appraisal and Current Status.
AB  - The recent explosion of technology has moved the field of patient reported
      outcomes (PROs) into a new era. Use of paper-and-pencil questionnaires
      administered before and after treatment has been eclipsed by highly sophisticated
      random prompts for symptom ratings at multiple points throughout the day, a
      method known as ecological momentary assessment (EMA). During the last 25 years,
      research has demonstrated that retrospective ratings are subject to a variety of
      cognitive heuristics that can distort the report. Initially, this was addressed
      by adopting paper diary protocols involving multiple ratings in a day or across a
      week. Technology was also advancing, and some researchers began to utilize
      electronic platforms for EMA assessment. A good deal of research has been
      conducted comparing paper and electronic formats. Issues of compliance have been
      particularly problematic for paper diaries. Electronic technologies can be
      expensive and require expertise in programming and data management. Not all
      research questions will require intensive momentary assessment, and end-of-day
      ratings may be adequate for many applications. What is required of the
      investigator is familiarity with the strengths and weaknesses of the methods and
      platforms available as well as a reasoned decision to elect a particular
      methodology for the study question at hand.

PMID- 20037674
TI  - Diagnostic Measures for Generalized Linear Models with Missing Covariates.
AB  - In this paper, we carry out an in-depth investigation of diagnostic measures for
      assessing the influence of observations and model misspecification in the
      presence of missing covariate data for generalized linear models. Our diagnostic
      measures include case-deletion measures and conditional residuals. We use the
      conditional residuals to construct goodness-of-fit statistics for testing
      possible misspecifications in model assumptions, including the sampling
      distribution. We develop specific strategies for incorporating missing data into
      goodness-of-fit statistics in order to increase the power of detecting model
      misspecification. A resampling method is proposed to approximate the p-value of
      the goodness-of-fit statistics. Simulation studies are conducted to evaluate our
      methods and a real data set is analysed to illustrate the use of our various
      diagnostic measures.

PMID- 20037675
TI  - Implementation and use of a web-based interface for confidential communication of
      data between the clinical and research environments.
AB  - Policies and regulations in the current health care environment have impacted the
      manner in which patient data - especially protected health information (PHI) -
      are handled in the clinical and research settings. Specifically, it is now more
      challenging to obtain de-identified PHI from the clinic for use in research while
      still adhering to the requirements dictated by the new policies and regulations.
      To meet this challenge, we have designed and implemented a novel web-based
      interface that uses a workflow model to manage the communication of data (for
      example, biopsy results) between the clinic and research environments without
      revealing PHI to the research team or associated research identifiers to the
      clinical collaborators. At the heart of the scheme is a web application that
      coordinates message passing between researchers and clinical collaborators by use
      of a protocol that protects confidentiality. We describe the design requirements
      of the messaging/communication protocol, as well as implementation details of the
      web application and its associated database. We conclude that this scheme
      provides a useful communication mechanism that facilitates clinical research
      while maintaining confidentiality of patient data.

PMID- 20037676
TI  - Dentin Sialophophoprotein (DSPP) and Dentin.
AB  - The revolution in genetics disclosed the types of malformations that occur when
      expression of a particular gene is lost. In the case of tooth dentin, mutations
      in the two genes encoding type I collagen cause osteogenesis imperfecta, a bone
      condition that often includes dentin malformations. Besides collagen, there are a
      number of non-collagenous proteins in dentin. Among the genes encoding the dentin
      non-collagenous proteins, only mutations in DSPP (dentin sialophosphoprotein)
      cause inherited dental malformations. DSPP mutations cause dentinogenesis
      imperfecta types II and III, and dentin dysplasia type II. DSPP is the most
      abundant non-collagenous protein in dentin. DSPP protein is necessary for proper
      dentin formation, and understanding its structure and function should yield
      important insights into how dentin forms and biomineralization is controlled.
      DSPP is expressed and secreted by odontoblasts, the cells that make tooth dentin
      and that also maintain cell processes extending into the mineralized tissue.
      Following its secretion, DSPP is cleaved into smaller pieces by multiple
      extracellular proteases. For the last five years I have devoted myself to
      characterizing DSPP-derived proteins. DSPP is cleaved by proteases 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- 20037678
TI  - A divergent route towards single-chemical entity triazine dendrimers with
      opportunities for structural diversity.
AB  - This manuscript describes the successful synthesis and characterization of five
      generations of dendrimers based on melamine. Early generations of these materials
      appear to be single chemical entities: upon purification, no detectable
      impurities are observed using NMR spectroscopy, mass spectrometry, and HPLC and
      GPC analysis. The analysis of larger generation materials precludes an
      unambiguous statement of purity. The synthetic route to these targets is
      divergent, relying on dichlorotriazine monomers that react with a polyamine
      dendrimer core of generation n to produce a poly(monochlorotriazine) dendrimer of
      generation n + 1. Subsequently, the poly(monochlorotriazine) is derivatized
      through nucleophilic aromatic substitution before additional nucleophilic amines
      are unmasked and the process iterated.

PMID- 20037679
TI  - Tiotropium HandiHaler in the treatment of COPD: a safety review.
AB  - BACKGROUND: Tiotropium is a long-acting inhaled anticholinergic developed for the
      treatment of chronic obstructive pulmonary disease (COPD) and has been available
      since 2002. We sought to update an evaluation of the safety of tiotropium in the
      HandiHaler formulation as significant clinical trial data have become available
      over time. METHODS: Pooled analysis of adverse event reporting from phase III and
      IV tiotropium HandiHaler clinical trials with the following characteristics was
      performed: randomized, double-blind, parallel group, placebo-controlled design,
      tiotropium 18 microg once-daily dosing, COPD indication, duration of at least
      four weeks. Incidence rates by treatment group, rate differences (tiotropium
      placebo), and 95% confidence intervals were determined. RESULTS: Twenty-six
      trials were identified involving 17,014 patients. Mean age was 65 years, mean
      forced expiratory volume in one second was 1.16 L (41% predicted), 76% men. Total
      exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient
      years (placebo). Tiotropium was associated with a reduced risk (expressed as rate
      difference [95% confidence interval] per 100 patients-years at risk) for an
      adverse event (-17.5 [-22.9, -12.2]), serious adverse event (-1.41 [-2.81, 
      0.00]) and a fatal event (-0.63 [-1.14, -0.12]). A reduced risk was present for
      adverse events that were cardiac (-0.79 [-1.48, -0.09]), lower respiratory (-14.2
      [-17.0, -11.5]) and for a composite endpoint of major adverse cardiovascular
      events (-0.45 [-0.85, -0.05]). Typical expected inhaled anticholinergic effects
      such as dry mouth, constipation, and urinary difficulties were observed in the
      safety database. CONCLUSION: The safety data review does not indicate an
      increased risk for death or cardiovascular morbidity during tiotropium treatment
      in patients with COPD.

PMID- 20037680
TI  - The pathophysiology of bronchiectasis.
AB  - Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This
      process occurs in the context of chronic airway infection and inflammation. It is
      usually diagnosed using computed tomography scanning to visualize the larger
      bronchi. Bronchiectasis is also characterized by mild to moderate airflow
      obstruction. This review will describe the pathophysiology of noncystic fibrosis
      bronchiectasis. Studies have demonstrated that the small airways in
      bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As
      most of the bronchial tree is composed of small airways, the net effect is
      obstruction. The bronchial wall is typically thickened by an inflammatory
      infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It
      has recently been demonstrated that patients with bronchiectasis have a
      progressive decline in lung function. There are a large number of etiologic risk
      factors associated with bronchiectasis. As there is generally a long-term
      retrospective history, it may be difficult to determine the exact role of such
      factors in the pathogenesis. Extremes of age and smoking/chronic obstructive
      pulmonary disease may be important considerations. There are a variety of
      different pathogens involved in bronchiectasis, but a common finding despite the
      presence of purulent sputum is failure to identify any pathogenic microorganisms.
      The bacterial flora appears to change with progression of disease.

PMID- 20037681
TI  - Clinical utility of varenicline for smokers with medical and psychiatric
      comorbidity.
AB  - Chronic obstructive pulmonary disease (COPD) is a costly and deadly disease
      afflicting an estimated 210 million people and accounting for 5% of all global
      deaths. Exposure to cigarette smoke is the greatest risk factor for COPD in the
      developed world. Smoking cessation improves respiratory symptoms and lung
      function and reduces mortality among patients with COPD. Cigarette smokers with
      COPD and other co-morbid conditions such as cardiovascular disease and
      psychiatric illnesses should receive comprehensive tobacco treatment
      interventions incorporating efficacious pharmacotherapies. Varenicline, an
      alpha(4)beta(2) nicotinic acetylcholine receptor partial agonist, is the newest
      and most effective drug currently available to promote smoking cessation. In
      conjunction with behavioral interventions and clinical monitoring for potential
      side effects, varenicline offers great hope for reducing smoking-attributable
      death and disability.

PMID- 20037682
TI  - Predictive value and utility of oral steroid testing for treatment of COPD in
      primary care: the COOPT study.
AB  - BACKGROUND: The oral prednisolone test is widely used to distinguish chronic
      obstructive pulmonary disease (COPD) patients who might benefit from inhaled
      steroid treatment. Previous studies used selected patient groups that did not
      represent the large COPD population in primary care. METHODS: The study included
      smokers and exsmokers with chronic bronchitis or COPD from primary care, who
      underwent prednisolone testing (30 mg for 14 days) before randomization in a
      three-year follow-up randomized controlled trial (COOPT Study). Spirometry was
      performed before and after the test. Responders and nonresponders were classified
      according to international criteria. Effectiveness of inhaled fluticasone
      relative to placebo was compared in terms of health status (Chronic Respiratory
      Disease Questionnaire), exacerbations, and postbronchodilator forced expiratory
      volume in one second (FEV(1)), using repeated measurement analysis. RESULTS: Two
      hundred eighty-six patients recruited from 44 primary care practices were
      randomized. Nine percent to 16% of the COPD population was classified as
      responder, depending on the international guideline criteria used. On average,
      responders did not reach the minimum clinically important difference in health
      status (0.29 points/year, P = 0.05), although a borderline significant effect of
      inhaled fluticasone was noted. Possible clinically relevant reductions in
      exacerbation rate (rate ratio 0.67) and FEV(1) decline (39 mL/year) occurred in
      responders, but did not reach statistical significance. CONCLUSIONS: Oral steroid
      testing identifies a limited proportion of COPD patients, but does not reveal any
      clinically relevant benefit from inhaled steroid treatment on health status. No
      significant effects on exacerbation rate and lung function decline occurred.

PMID- 20037684
TI  - Forging our future.

PMID- 20037683
TI  - Can dead space fraction predict the length of mechanical ventilation in
      exacerbated COPD patients?
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a condition in which
      there is limited airflow during expiration (exhaling, or breathing out) that is
      not fully reversible and usually worsens over time. The disease is estimated to
      kill more than 100,000 Americans each year, and costs related to care of patients
      with COPD are significant. Physiologically, COPD represents a disruption in
      ventilation and in the exchange of gases in the lungs. Laboratory tests indicate
      elevated CO2 levels, gradual reduction of the levels of oxygen and pH in arterial
      blood, and a consequent rise in the dead space fraction (DSF) of the lungs.
      OBJECTIVE: Patients with COPD exacerbation represent a large portion of those
      artificially ventilated. In an attempt to develop a prognostic tool for length of
      treatment, we compared the proportion of DSF to the length of mechanical
      ventilation (MV). METHODS: This study included 73 patients admitted to the
      intensive care unit (ICU) where they received MV due to exacerbation of COPD.
      Each patient's arterial blood gases (ABG) were measured upon admission. PeCO2 was
      tested using a Datex S/5 instrument. Subsequently, DSF was calculated using the
      Bohr equation. Statistical data was analyzed using SPSS software. RESULTS:
      Patients included in the study were ventilated from 6 to 160 hours (average 40 +/
      47). In addition to ABG measurements, PeCO2 (expired CO2) levels were measured
      and DSF calculated for each patient. DSF values varied from 0.21 to 0.76 (average
      0.119 +/- 0.489). No correlation was found between DSF and length of artificial
      ventilation. CONCLUSION: Evaluation of DSF does not provide a factor in
      estimating the length of treatment for patients with acute respiratory failure
      due to COPD exacerbation.

PMID- 20037685
TI  - JCCA Editorial Board.

PMID- 20037686
TI  - Profile.

PMID- 20037687
TI  - Chiropractic research capacity in Canada in 2008 - Phase 3.

PMID- 20037688
TI  - Sports chiropractic in Canada.

PMID- 20037689
TI  - The ability of parents to accurately report concussion occurrence in their bantam
      aged minor hockey league children.
AB  - OBJECTIVE: The objective of this study was to assess the ability of hockey
      parents/guardians to recognize concussion symptoms in their 13-14 year old
      (Bantam-aged) children. OUTCOME MEASURES: The outcome measures were the ability
      to recognize different signs and symptoms listed on the Sport Concussion
      Assessment Tool (SCAT) as well as 8 detractors consisting of signs and symptoms
      not associated with post concussive syndrome. Additional questions assessing the
      parents' knowledge of concussion management and recognition abilities were also
      posed. PARTICIPANTS: Parents of Bantam-aged minor hockey league athletes
      volunteered for the study. METHODS: The study investigators distributed
      questionnaires during the warm up period or following their children's games to
      the study participants. Following questionnaire completion, participants were
      provided with an information package outlining the correct signs and symptoms of
      concussion. RESULTS: The mean number of correct responses to signs and symptoms
      of concussion was 21.25/25 for the mothers and 20.41/25 for the fathers. The mean
      number of detractors identified as not associated with concussion was 5.93/8 for
      the mothers and 4.85/8 for the fathers, indicating that mothers were more capable
      of recognizing the signs and symptoms than fathers. An analysis of variance
      including sporting experience in the model did not strengthen the relationship
      between parent gender and test outcome. CONCLUSION: This investigation revealed
      that there is still a disconnect in regards to key components of recognizing a
      concussion, such as difficulty with sleep, disorientation symptoms, and emotional
      irritability. Mothers have displayed an ability to better differentiate between
      true and false signs and symptoms of concussion as compared to fathers. Continued
      education and awareness of mild traumatic brain injury in athletes should address
      the misconceptions amongst parents in regards to the true signs and symptoms of a
      concussion.

PMID- 20037690
TI  - Exercise related transient abdominal pain: a case report and review of the
      literature.
AB  - Exercise-related transient abdominal pain (ETAP) is more commonly known to
      athletes as a runner's stitch. Many athletes also report shoulder tip pain (STP)
      associated with the ETAP. Although widely known, ETAP remains under analyzed and
      under reported in the medical literature. Often thought of as benign and self
      limiting, ETAP has been shown to be very detrimental to the performance of many
      athletes from novice to elite. This case report of an elite triathlete with ETAP
      and subsequent review of literature, outlines the various theories about the
      etiology of ETAP, the epidemiology associated with it, some differentials to
      consider, and how chiropractic care may benefit those suffering from ETAP.

PMID- 20037691
TI  - Traumatic anterior shoulder dislocation: a case study of nonoperative management
      in a mixed martial arts athlete.
AB  - OBJECTIVE: To present an evidence-informed approach to the nonoperative
      management of a first-time, traumatic anterior shoulder dislocation. CLINICAL
      FEATURES: A 30-year-old mixed martial arts athlete, with no prior shoulder
      injuries, presented one day following a first-time, traumatic anterior shoulder
      dislocation. An eight-week, individualized, intensive, nonoperative
      rehabilitation program was immediately begun upon presentation. INTERVENTION AND
      OUTCOME: Management consisted of immobilization of the shoulder in external
      rotation and a progressive rehabilitation program aimed at restoring range of
      motion, strength of the dynamic stabilizers, and proprioception of the shoulder.
      Eight weeks post-dislocation the patient had regained full range of motion and
      strength compared to the unaffected limb and apprehension and relocation tests
      for instability were negative. CONCLUSION: This case illustrates successful
      management of a first-time, traumatic, anterior shoulder dislocation using
      immobilization in external rotation combined with an intensive rehabilitation
      program.

PMID- 20037692
TI  - Nine year longitudinal retrospective study of Taekwondo injuries.
AB  - This retrospective longitudinal study aims to describe reported Taekwondo
      injuries and to examine associations between competitor experience level, age and
      gender, and the type, location, and mechanism of injury sustained. Additionally,
      we examined whether recent rule changes concerning increased point value of head
      shots in adult Taekwondo competition had affected injury incidence.This study was
      a summation of 9 years of data of competition injury reports, which included 904
      injury reports spanning 58 individual competitions. The data was collected on
      standardized injury reports at time of injury during competition. Care was
      provided to the athletes, but the type of care provided was not included in the
      study. Participants included athletes injured during competition who sought care
      by the health care team, and for whom an injury report was filled out. The data
      analysis was performed at the Canadian Memorial Chiropractic College.The three
      most common locations of presenting injury were the head (19%), foot (16%), and
      thigh (9%). The most common mechanism of presenting injury was found to be a
      defensive kick (44%), followed by an offensive kick (35%). The most commonly
      diagnosed injuries were contusions (36%), sprains (19%), and strains (15%).
      Coloured belts had a higher incidence of contusions, while black belts sustained
      more joint irritation injuries. Black belts were more likely to suffer multiple
      injuries. Colored belts suffered more injuries while receiving a kick, while
      black belts had a larger influence of past history of injury. We found no
      significant difference in location or type of injury when comparing pre versus
      post rule change. The most common locations of injury are head, foot, and thigh
      respectively, and are areas for concern when considering preventative measures.
      Colour belt competitors are more likely to sustain contusions, which the authors
      believe is due to more aggressive tactics and lack of control. Those more likely
      to be injured tend to be younger than 18 years. Recent rule changes have no
      significant effect on head injuries.

PMID- 20037693
TI  - Conservative management of symptomatic Carpal Bossing in an elite hockey player:
      a case report.
AB  - OBJECTIVE: To present the characteristics and create awareness of symptomatic
      carpal bossing and discuss potential etiologies and the role of conservative
      management through the presentation of an athlete with traumatic onset of
      symptomatic carpal bossing. CLINICAL FEATURES: This case report outlines the
      presentation and conservative management of an elite eighteen year old hockey
      player with symptomatic carpal bossing after a traumatic on ice collision. Carpal
      bossing is a bony, dorsal prominence in the quadrangular joint of the wrist that
      is inconsistently symptomatic. INTERVENTION AND OUTCOME: A conservative treatment
      plan consisting of education, reassurance, avoidance of aggravation, and soft
      tissue therapy allowed return to play in two weeks without restrictions or need
      for surgical consultation. CONCLUSION: With inconsistent recurrence rates and
      surgical complications, the role of conservative management for symptomatic
      carpal bossing deserves further exploration. The conservative practitioner should
      be aware of the signs and symptoms of symptomatic carpal bossing to institute
      suitable treatment.

PMID- 20037694
TI  - Golf-related stress fractures: a structured review of the literature.
AB  - BACKGROUND: Stress fractures are troublesome injuries. Sites of occurrence are
      activity-related and specific anatomical sites are endemic to certain sports.
      Little is known about stress fracture patterns in golf. OBJECTIVE: A structured
      review of the literature was conducted to identify the occurrence and injury
      sites of golf-related stress fractures. METHODS: A literature search of MEDLINE,
      CINAHL, and SPORTDiscus was conducted using a combination of controlled
      vocabulary and truncated text words to capture all articles relevant to golf
      related stress fractures. Articles meeting inclusion criteria were descriptively
      analyzed. RESULTS: The search resulted in 164 articles, of which 13 met the
      inclusion, and reported 44 cases of golf-related stress fractures. Seven
      anatomical injury sites were identified with rib stress fracture being the most
      commonly reported. Stress fractures occurred on the golfer's lead-side in 80% of
      cases. CONCLUSION: Golf-related stress fractures are infrequent injuries. The
      ribs were the most common stress fracture site, and a predilection for lead-side
      involvement was reported.

PMID- 20037695
TI  - Conservative management of posterior interosseous neuropathy in an elite baseball
      pitcher's return to play: a case report and review of the literature.
AB  - This report documents retrospectively a case of Posterior Interosseous Neuropathy
      (PIN) occurring in an elite baseball pitcher experiencing a deep ache in the
      radial aspect of the forearm and altered sensation in the dorsum of the hand on
      the throwing arm during his pitching motion. The initial clinical goal was to
      control for inflammation to the nerve and muscle with active rest, microcurrent
      therapy, low-level laser therapy, and cessation of throwing. Minimizing
      mechanosensitivity at the common extensor region of the right elbow and PIN, was
      achieved by employing the use of myofascial release and augmented soft tissue
      mobilization techniques. Neurodynamic mobilization technique was also
      administered to improve neural function. Implementation of a sport specific
      protocol for the purposes of maintaining throwing mechanics and overall
      conditioning was utilized. Successful resolution of symptomatology and return to
      pre-injury status was achieved in 5 weeks. A review of literature and an evidence
      based discussion for the differential diagnoses, clinical examination, diagnosis,
      management and rehabilitation of PIN is presented.

PMID- 20037696
TI  - Psoas Major: a case report and review of its anatomy, biomechanics, and clinical
      implications.
AB  - A 25-year-old male professional hockey player with right sided hip pain was
      diagnosed with myofascopathy of the right psoas major and rectus femoris. The
      patient maintained a conservative treatment regimen and was prescribed a four
      week active strengthening program. The program progressed from resisted
      concentric exercise to eccentric abduction/adduction exercises along with balance
      training, core stabilizing and endurance exercises in the first two weeks. In the
      final two weeks the program progressed to include sport specific exercises. At
      three weeks the patient was able to participate in non-contact practice and was
      clear for full contact at five weeks. The anatomy, biomechanics, and function of
      the psoas major muscle are discussed as is its influence on lumbar spine
      stability. Evidence-based evaluation and management strategies for psoas
      dysfunction are presented.

PMID- 20037697
TI  - Anatomy and physical examination of the knee menisci: a narrative review of the
      orthopedic literature.
AB  - OBJECTIVE: The objective of this study was to review the physical examination
      tests available to a practitioner in order to arrive at a clinical diagnosis or
      suspicion of a meniscal lesion. BACKGROUND: The menisci transmit weight bearing
      forces and increase stability of the knee. The menisci also facilitate nutrition,
      provide lubrication and shock absorption for the articular cartilage and promote
      knee proprioception. The combinations of torsional and axial loading appear to be
      the cause of most meniscal injuries. Diagnosis of acute knee injuries has long
      been a topic for discussion throughout the orthopedic literature. Many clinical
      tests and diagnostic studies have been developed to increase the clinician's
      ability to accurately diagnose these types of disorders of the knee. CONCLUSION:
      The accuracy of all diagnostic tests is thought to be dependant upon the skill of
      the examiner, and the severity and location of the injury. The multitude of tests
      described to assess meniscal lesions suggests that none are consistently
      reliable. However, recent research has focused on a composite score to accurately
      predict meniscus lesions. The combination of a comprehensive history, multiple
      physical tests and diagnostic imaging for confirmation is typical for a clinical
      meniscal lesion diagnosis while the gold standard remains the arthroscopic
      procedure itself.

PMID- 20037698
TI  - Ganglion cyst on the posterior cruciate ligament: a case report.
AB  - OBJECTIVE: To present the diagnostic and clinical features of a ganglion cyst
      located on the posterior cruciate ligament and create awareness amongst
      clinicians of this uncommon diagnosis. CLINICAL FEATURES: A 24-year old woman
      complaining of intermittent left knee pain brought on by an increase in mileage
      during her training for a half-marathon. A diagnosis of mild chondromalacia
      patella and a ganglion cyst on the posterior cruciate ligament was made via
      diagnostic imaging. INTERVENTION AND OUTCOME: Patient was followed up with
      imaging. The patient chose to withdraw a surgical consult due to patient
      preference. No conservative treatment was provided. CONCLUSION: Although
      chondromalacia patella is the more probable, a secondary diagnostic consideration
      in this patient could be a ganglion cyst. A ganglion cyst on the posterior
      cruciate ligament is an uncommon diagnosis and the clinical manifestations are
      variable and non-specific. It is important to be aware of its clinical features
      and to obtain appropriate methods of imaging to generate the diagnosis promptly.

PMID- 20037700
TI  - Predictive success factors for CT-guided fine needle aspiration biopsy of
      pulmonary lesions.
AB  - OBJECTIVE: Computed tomography-guided percutaneous fine needle aspiration biopsy
      of lung lesions is a simple, safe and reproducible procedure. Currently, it is
      widely used to diagnose lung lesions. However, different factors can influence
      the success rates of this procedure. The purpose of this study was to determine
      the influence of radiological and procedural characteristics in predicting the
      success rates of computed tomography-guided fine needle aspiration biopsy of lung
      lesions. SUBJECTS AND METHODS: A retrospective study was developed and involved
      340 patients who were submitted to a consecutive series of 362 computed
      tomography-guided fine needle aspiration biopsies of lung lesions, between July
      1996 and June 2004, using 22-gauge needles (Chiba). Variables such as the
      radiological characteristics of the lesions, secondary pulmonary radiological
      findings, and procedural techniques were studied. RESULTS: For this study, 304
      (84%) fine needle aspiration biopsies of lung lesions provided sufficient
      material for cytological evaluation. The variables that predicted sufficient
      material for cytological evaluation were lesions larger than 40 mm (p=0.02),
      lesions on the superior lung lobes (p=0.02), and suspicion of primary lung
      malignancy (p=0.03). From the multivariate analysis, the only predictive variable
      for success of the biopsies was localization on the superior lobes (p=0.01).
      CONCLUSIONS: Computed tomography-guided percutaneous fine needle aspiration
      biopsy of lung lesions showed greater rates of success in biopsies performed in
      patients with suspicion of primary lung malignancy, with lesions located in the
      superior lobes, and that have diameters equal to and larger than 40 mm.

PMID- 20037701
TI  - Diagnosis of regional cerebral blood flow abnormalities using spect: agreement
      between individualized statistical parametric maps and visual inspection by
      nuclear medicine physicians with different levels of expertise in nuclear
      neurology.
AB  - INTRODUCTION: Visual analysis is widely used to interpret regional cerebral blood
      flow (rCBF) SPECT images in clinical practice despite its limitations. Automated
      methods are employed to investigate between-group rCBF differences in research
      studies but have rarely been explored in individual analyses. OBJECTIVES: To
      compare visual inspection by nuclear physicians with the automated statistical
      parametric mapping program using a SPECT dataset of patients with neurological
      disorders and normal control images. METHODS: Using statistical parametric
      mapping, 14 SPECT images from patients with various neurological disorders were
      compared individually with a databank of 32 normal images using a statistical
      threshold of p<0.05 (corrected for multiple comparisons at the level of
      individual voxels or clusters). Statistical parametric mapping results were
      compared with visual analyses by a nuclear physician highly experienced in
      neurology (A) as well as a nuclear physician with a general background of
      experience (B) who independently classified images as normal or altered, and
      determined the location of changes and the severity. RESULTS: Of the 32 images of
      the normal databank, 4 generated maps showing rCBF abnormalities (p<0.05,
      corrected). Among the 14 images from patients with neurological disorders, 13
      showed rCBF alterations. Statistical parametric mapping and physician A
      completely agreed on 84.37% and 64.28% of cases from the normal databank and
      neurological disorders, respectively. The agreement between statistical
      parametric mapping and ratings of physician B were lower (71.18% and 35.71%,
      respectively). CONCLUSION: Statistical parametric mapping replicated the findings
      described by the more experienced nuclear physician. This finding suggests that
      automated methods for individually analyzing rCBF SPECT images may be a valuable
      resource to complement visual inspection in clinical practice.

PMID- 20037702
TI  - Analysis of the sputum and inflammatory alterations of the airways in patients
      with common variable immunodeficiency and bronchiectasis.
AB  - INTRODUCTION: Common variable immunodeficiency is characterized by defective
      antibody production and recurrent pulmonary infections. Intravenous
      immunoglobulin is the treatment of choice, but the effects of Intravenous
      immunoglobulin on pulmonary defense mechanisms are poorly understood. OBJECTIVE:
      The aim of this study was to verify the impact of intravenous immunoglobulin on
      the physical properties of the sputum and on inflammatory alterations in the
      airways of patients with Common variable immunodeficiency associated with
      bronchiectasis. METHOD: The present study analyzed sputum physical properties,
      exhaled NO, inflammatory cells in the sputum, and IG titers in 7 patients with
      Common variable immunodeficiency and bronchiectasis with secretion, immediately
      before and 15 days after Intravenous immunoglobulin. A group of 6 patients with
      Common variable immunodeficiency and bronchiectasis but no sputum was also
      studied for comparison of the basal IgG level and blood count. The 13 patients
      were young (age=36+/-17 years) and comprised predominantly of females (n=11).
      RESULTS: Patients with secretion presented significantly decreased IgG and IgM
      levels. Intravenous immunoglobulin was associated with a significant decrease in
      exhaled NO (54.7 vs. 40.1 ppb, p<0.05), sputum inflammatory cell counts (28.7 vs.
      14.6 cells/mm(3), p<0.05), and a significant increase in respiratory mucus
      transportability by cough (42.5 vs. 65.0 mm, p < 0.05). CONCLUSION: We concluded
      that immunoglobulin administration in Common variable immunodeficiency patients
      results in significant improvement in indexes of inflammation of the airways with
      improvement in the transportability of the respiratory mucus by cough.

PMID- 20037703
TI  - How is mechanical ventilation employed in a pediatric intensive care unit in
      Brazil?
AB  - OBJECTIVE: To investigate the relationship between mechanical ventilation and
      mortality and the practice of mechanical ventilation applied in children admitted
      to a high-complexity pediatric intensive care unit in the city of Sao Paulo,
      Brazil. DESIGN: Prospective cohort study of all consecutive patients admitted to
      a Brazilian high-complexity PICU who were placed on mechanical ventilation for 24
      hours or more, between October 1(st), 2005 and March 31(st), 2006. RESULTS: Of
      the 241 patients admitted, 86 (35.7%) received mechanical ventilation for 24
      hours or more. Of these, 49 met inclusion criteria and were thus eligible to
      participate in the study. Of the 49 patients studied, 45 had chronic functional
      status. The median age of participants was 32 months and the median length of
      mechanical ventilation use was 6.5 days. The major indication for mechanical
      ventilation was acute respiratory failure, usually associated with severe sepsis
      / septic shock. Pressure ventilation modes were the standard ones. An overall
      10.37% incidence of Acute Respiratory Distress Syndrome was found, in addition to
      tidal volumes > 8 ml/kg, as well as normo- or hypocapnia. A total of 17 children
      died. Risk factors for mortality within 28 days of admission were initial
      inspiratory pressure, pH, PaO2/FiO2 ratio, oxygenation index and also oxygenation
      index at 48 hours of mechanical ventilation. Initial inspiratory pressure was
      also a predictor of mechanical ventilation for periods longer than 7 days.
      CONCLUSION: Of the admitted children, 35.7% received mechanical ventilation for
      24 h or more. Pressure ventilation modes were standard. Of the children studied,
      91% had chronic functional status. There was a high incidence of Acute
      Respiratory Distress Syndrome, but a lung-protective strategy was not fully
      implemented. Inspiratory pressure at the beginning of mechanical ventilation was
      a predictor of mortality within 28 days and of a longer course of mechanical
      ventilation.

PMID- 20037704
TI  - The development and validation of a Low Back Pain Knowledge Questionnaire - LKQ.
AB  - OBJECTIVE: The objective of this study was to develop and validate a
      questionnaire on specific knowledge about low back pain entitled "The Low Back
      Pain Knowledge Questionnaire". INTRODUCTION: There is a need for instruments to
      assess patient knowledge regarding chronic illness. Such methods can contribute
      to the education of patients. METHODS: The Low Back Pain Knowledge Questionnaire
      was developed through five focus groups. The questionnaire was distributed to 50
      patients to assess their comprehension of the terms. To assess the
      reproducibility, 20 patients were surveyed by two different interviewers on the
      same day and twice by a single interviewer with a one-to-two week interval. For
      the construct validation, the Low Back Pain Knowledge Questionnaire was given to
      20 healthcare professionals with knowledge on low back pain and 20 patients to
      determine whether the questionnaire would discriminate between the two different
      populations. To assess the sensitivity of the questionnaire to changes in the
      knowledge level of the patients, it was given to 60 patients who were randomly
      assigned to the Intervention Group and the Control Group. The Intervention Group
      answered the questionnaire both before and after attending a chronic back pain
      educational program (back school), whereas the Control Group answered the
      questionnaire twice with an interval of one month and no educational
      intervention. RESULTS: The focus groups generated a questionnaire with 16 items.
      The Spearman's correlation coefficient and the intra-class correlation
      coefficients ranged from 0.61 to 0.95 in the assessments of the intra-observer
      and inter-observer reproducibility (p< 0.01). In the construct validation, the
      healthcare professionals and patients showed statistically different scores (p<
      0.001). In the phase regarding the sensitivity to change, the Intervention Group
      exhibited a significant increase in their specific knowledge over the Control
      Group (p< 0.001). CONCLUSION: The Low Back Pain Knowledge Questionnaire was
      validated and proved to be reproducible, valid and sensitive to changes in
      patient knowledge.

PMID- 20037705
TI  - Prognostic factors in the survival of patients diagnosed with primary non
      metastatic osteosarcoma with a poor response to neoadjuvant chemotherapy.
AB  - INTRODUCTION: Identification of variables that determine the prognosis for
      osteosarcoma may enable stratification of patients into subgroups with better or
      worse risk of local recurrence, metastases and death due to the disease.
      Discovery of such prognostic factors would permit selection of a subgroup of at
      risk patients, with the aim of improving the therapeutic effectiveness.
      OBJECTIVE: To identify prognostic factors related to local recurrence-free
      survival, metastasis-free survival and overall survival among patients with
      highly malignant primary osteosarcoma that was non-metastatic on diagnosis and
      had poor response to neoadjuvant chemotherapy. SAMPLE AND METHODS: Out of 45
      patients admitted to a referral center in Brazil between 2000 and 2004, 24 were
      selected for this study. RESULTS: The adverse factors that influenced the risk of
      local recurrence and the overall survival in univariate analysis were
      histological subtype other than osteoblastic (p = 0.017) and tumor size greater
      than 15 cm (p = 0.048). In relation to metastasis-free survival, the non
      osteoblastic subtype had a worse prognosis (p = 0.007). The association of
      histological subtype maintained its significance in multivariate analysis for all
      studied survival categories. CONCLUSIONS: Tumor size greater than 15 cm is an
      adverse factor for local recurrence-free survival and overall survival but did
      not influence metastasis-free survival. The osteosarcoma histological type is a
      significant independent predictor for local recurrence-free survival, metastasis
      free survival and overall survival.

PMID- 20037706
TI  - Effectiveness of radiation synovectomy with samarium-153 particulate
      hydroxyapatite in rheumatoid arthritis patients with knee synovitis: a controlled
      randomized double-blind trial.
AB  - OBJECTIVES: The aim of the present study was to investigate the effectiveness of
      Samarium(153)-particulate hydroxyapatite radiation synovectomy in rheumatoid
      arthritis patients with chronic knee synovitis. METHODS: Fifty-eight rheumatoid
      arthritis patients (60 knees) with chronic knee synovitis participated in a
      controlled double-blinded trial. Patients were randomized to receive either an
      intra-articular injection with 40 mg triamcinolone hexacetonide alone (TH group)
      or 40 mg triamcinolone hexacetonide combined with 15 mCi Samarium(153)
      particulate hydroxyapatite (Sm/TH group). Blinded examination at baseline (T0)
      and at 1 (T1), 4 (T4), 12 (T12), 32 (T32), and 48 (T48) weeks post-intervention
      were performed on all patients and included a visual analog scale for joint pain
      and swelling as well as data on morning stiffness, flexion, extension, knee
      circumference, Likert scale of improvement, percentage of improvement, SF-36
      generic quality of life questionnaire, Stanford Health Assessment Questionnaire
      (HAQ), Lequesne index, use of non-steroidal anti-inflammatory drugs or oral
      corticosteroids, events and adverse effects, calls to the physician, and hospital
      visits. RESULTS: The sample was homogeneous at baseline, and there were no
      withdrawals. Improvement was observed in both groups in relation to T0, but no
      statistically significant differences between groups were observed regarding all
      variables at the time points studied. The Sm/TH group exhibited more adverse
      effects at T1 (p<0.05), but these were mild and transitory. No severe adverse
      effects were reported during follow-up. CONCLUSION: Intra-articular injection of
      Samarium(153)-particulate hydroxyapatite (15 mCi) with 40 mg of triamcinolone
      hexacetonide is not superior to triamcinolone hexacetonide alone for the
      treatment of knee synovitis in patients with rheumatoid arthritis at 1 y of
      follow-up.

PMID- 20037707
TI  - Autoantibody frequency in celiac disease.
AB  - AIM: In our study, we investigated the levels of glutamic acid decarboxylase
      antibody (anti-GAD), islet cell antibody (ICA), thyroperoxidase antibody (anti
      TPO), thyroglobulin antibody (anti-TG), antinuclear antibodies (FANA), antibodies
      to double-stranded DNA (anti-ds DNA), antibody to Sjogren syndrome A antigen
      (anti-SSA), antibody to Sjogren syndrome B antigen (anti-SSB), Smith antibody
      (anti-Sm), smooth muscle antibodies (ASMA), and antimitochondrial antibody liver
      kidney microsome (AMA-LKM) in patients with celiac disease as compared to healthy
      controls and autoimmune hypothyroid patients. MATERIALS AND METHODS: A total of
      31 patients with celiac disease, 34 patients with autoimmune hypothyroidism and
      29 healthy subjects were included in this study. Anti-SSA, anti-SSB, anti-Sm,
      anti-ds DNA, anti-GAD, anti-TPO and anti-TG were studied by Enzyme-Linked
      Immunosorbent Assay (ELISA), and AMA-LKM, ASMA, ANA and ICA were studied by
      immunofluorescence. Clinical data and the results of free thyroxine-thyroid
      stimulating hormone (FT4-TSH) were collected from the patients' files by
      retrospective analysis. SPSS ver 13.0 was used for data analysis, and the chi(2)
      method was used for comparisons within groups. RESULTS: The frequency of anti
      SSA, anti-SSB, anti-GAD, anti-Sm, anti-ds DNA, AMA-LKM, ASMA, ANA and ICA were
      not significantly different between the groups. Levels of anti-TPO and anti-TG
      antibodies were found to be significantly higher (<0.001) in autoimmune
      hypothyroid patients when compared with other groups. CONCLUSION: In previous
      studies, an increased frequency of autoimmune diseases of other systems has been
      reported in patients with celiac disease. We found that the frequency of
      autoimmune antibodies specific for other autoimmune diseases was not higher in
      celiac disease.

PMID- 20037708
TI  - Identification and treatment of osteoporosis among elderly patients with hip
      fractures.
AB  - OBJECTIVE: To evaluate the profile of osteoporosis treatment among patients
      hospitalized due to hip fractures at a tertiary-level university hospital. To
      compare the impact of hospitalization on approaches toward treating bone mass
      losses. METHOD: The medical records of 123 hip fracture patients aged 60 years
      and over at the Institute of Orthopedics, Hospital das Clinicas, University of
      Sao Paulo School of Medicine, between 2004 and 2006 were reviewed and analyzed
      with respect to approaches towards investigating osteoporosis and treatments
      before and after fracture. RESULTS: The patients' mean age was 78 +/- 8.3 years,
      and the majority were women (71.54%). The patients had a mean of 2.72
      comorbidities and used 3.26 medications on average. Among these patients, 12.3%
      reported a previous diagnosis of osteoporosis, and 5.83% were on medication for
      this. The mean waiting time for surgery was 6.3 +/- 7.54 days, and seven patients
      (5.7%) died during the hospitalization. There were no investigations using bone
      densitometry, no changes in osteoporosis therapy between admission and discharge
      (p = 0.375), and no reports of referrals for the patient to have access to
      treatment. CONCLUSIONS: Investigations and treatments of osteoporosis and
      strategies for preventing new fractures were not implemented during the
      hospitalization of these elderly patients with hip fractures, even though this is
      the most feared complication of osteoporosis. These data need to be disseminated
      so that professionals dealing with elderly patients are attentive to the need for
      primary and secondary prevention of osteoporosis because of the impact of
      fractures on these patients' quality of life, independence, morbidities, and
      mortality.

PMID- 20037709
TI  - Sleep in infants with congenital heart disease.
AB  - OBJECTIVES: To investigate hypoxia and sleep disordered breathing in infants with
      congenital heart disease. METHODS: Prospective study. In-hospital full
      polysomnography was performed on 14 infants with congenital heart disease, age 7
      +/-1 months, and in 7 normal infants, age 10 +/-2 months. Congenital heart
      disease infants were classified as acyanotic (n=7) or cyanotic (n=7). RESULTS:
      Nutritional status, assessed by the Gomez classification and expressed as %
      weight for age, was 70 +/-7, 59 +/-11 and 94 +/-16 in the acyanotic, cyanotic
      congenital heart disease and control infants, respectively (p<0.001). The
      respiratory disturbance index (AHI, events per hour) was [median (25-75%)]: 2.5
      (1.0-3.4), 2.4 (1.5-3.1) and 0.7 (0.7-0.9) in acyanotic, cyanotic CHD infants and
      controls, respectively (p=0.013). Almost all congenital heart disease infants (11
      out of 14) and only one control infant had an AHI >1 event/hour. The minimum
      oxygen saturation was 79% (74-82), 73% (57-74) and 90% (90-91) in the acyanotic,
      cyanotic congenital heart disease infants and controls, respectively (p <0.001).
      The arousal index (events/hour) was similar among the three groups at 8.4 +/-2.4,
      10.3 +/-8.7 and 6.5 +/-3, respectively (p=0.451). CONCLUSIONS: Infants with
      congenital heart disease frequently present with sleep-disordered breathing
      associated with oxygen desaturations but not arousals. Therefore, sleep may
      represent a significant burden to infants with congenital heart disease.

PMID- 20037710
TI  - Ascorbic acid protects against restraint stress-induced memory deficits in Wistar
      rats.
AB  - OBJECTIVE: Chronic stress has been shown to cause oxidative damage in the central
      nervous system. Although stress-induced impairments in learning and memory have
      been studied extensively, very few studies have investigated possible ways to
      prevent their ill effects. The present work was designed to study the protective
      effects of ascorbic acid in memory loss induced by chronic restraint stress.
      METHODS: Adult male Wistar rats were designated into the following groups: (i)
      Normal control, (ii) Ascorbic acid treatment, (iii) Vehicle control, (iv)
      Restraint stress, (v) Restraint stress + vehicle, and (vi) Restraint stress +
      ascorbic acid treatment. At the end of 21 days, animals of all groups were
      subjected to memory tests using Morris water maze and passive avoidance
      apparatus. Then, the results obtained were compared between the experimental
      groups. RESULTS: Rats exposed to restraint stress alone and those pretreated with
      vehicle solution before restrained stress showed deficits in learning and
      impaired memory retention in the memory tests when compared to animals in other
      experimental groups. Animals pretreated with ascorbic acid before restraining
      showed significant improvement in memory retention in the same memory tests.
      CONCLUSIONS: Results of this study suggest the possibility of using ascorbic acid
      as a dietary supplement to prevent stress-induced memory impairments.

PMID- 20037712
TI  - Successful treatment of a resistance trigeminal neuralgia patient by acupuncture.

PMID- 20037711
TI  - The chronic gastrointestinal manifestations of Chagas disease.
AB  - Chagas disease is an infectious disease caused by the protozoan Trypanosoma
      cruzi. The disease mainly affects the nervous system, digestive system and heart.
      The objective of this review is to revise the literature and summarize the main
      chronic gastrointestinal manifestations of Chagas disease. The chronic
      gastrointestinal manifestations of Chagas disease are mainly a result of enteric
      nervous system impairment caused by T. cruzi infection. The anatomical locations
      most commonly described to be affected by Chagas disease are salivary glands,
      esophagus, lower esophageal sphincter, stomach, small intestine, colon,
      gallbladder and biliary tree. Chagas disease has also been studied in association
      with Helicobacter pylori infection, interstitial cells of Cajal and the incidence
      of gastrointestinal cancer.

PMID- 20037713
TI  - Chronic thrombosed abdominal aortic aneurysms: a report on three consecutive
      cases and literature review.

PMID- 20037714
TI  - Multiple perforations along the transverse colon as a rare presentation of
      intestinal Behcet's disease: a case report.

PMID- 20037715
TI  - Three-dimensional rotational angiography in murine models: a technical note.

PMID- 20037716
TI  - Evaluation of the efficacy and cross-protectivity of recent human and swine
      vaccines against the pandemic (H1N1) 2009 virus infection.
AB  - The current pandemic (H1N1) 2009 virus remains transmissible among humans
      worldwide with cases of reverse zoonosis, providing opportunities to produce more
      pathogenic variants which could pose greater human health concerns. To
      investigate whether recent seasonal human or swine H1N1 vaccines could induce
      cross-reactive immune responses against infection with the pandemic (H1N1) 2009
      virus, mice, ferrets or mini-pigs were administered with various regimens (once
      or twice) and antigen content (1.77, 3.5 or 7.5 microg HA) of a-Brsibane/59/07, a
      CAN01/04 or RgCA/04/09xPR8 vaccine. Receipt of a-CAN01/04 (2-doses) but not a
      Brisbane/59/07 induced detectable but modest (20-40 units) cross-reactive serum
      antibody against CA/04/09 by hemagglutinin inhibition (HI) assays in mice. Only
      double administration (7.5 microg HA) of both vaccine in ferrets could elicit
      cross-reactivity (30-60 HI titers). Similar antigen content of a-CAN01/04 in mini
      pigs also caused a modest approximately 30 HI titers (twice vaccinated). However,
      vaccine-induced antibody titers could not suppress active virus replication in
      the lungs (mice) or virus shedding (ferrets and pigs) of immunized hosts
      intranasally challenged with CA/04/09. Furthermore, neither ferrets nor swine
      could abrogate aerosol transmission of the virus into naive contact animals.
      Altogether, these results suggest that neither recent human nor animal H1N1
      vaccine could provide complete protectivity in all animal models. Thus, this
      study warrants the need for strain-specific vaccines that could yield the optimal
      protection desired for humans and/or animals.

PMID- 20037727
TI  - Matrix Metalloproteinase-9 (MMP9)-A Mediating Enzyme in Cardiovascular Disease,
      Cancer, and Neuropsychiatric Disorders.
AB  - Matrix metalloproteinase-9 (MMP9) has been implicated in numerous somatic
      illnesses, including cardiovascular disorders and cancer. Recently, MMP9 has been
      shown to be increasingly important in several aspects of central nervous system
      activity. Furthermore, a pathogenic role for this enzyme has been suggested in
      such neuropsychiatric disorders as schizophrenia, bipolar illness, and multiple
      sclerosis. In this paper, the results of biochemical and molecular-genetic
      studies on MMP9 that have been performed in these pathological conditions will be
      summarized. Furthermore, I hypothesize that the MMP9 gene, as shown by functional
      -1562 C/T polymorphism studies, may be mediating the relationship of
      neuropsychiatric illnesses (schizophrenia, bipolar mood disorder, multiple
      sclerosis) that are comorbid with cardiovascular disease and cancer.

PMID- 20037728
TI  - Isolation of osteosarcoma-associated human antibodies from a combinatorial Fab
      phage display library.
AB  - Osteosarcoma, a highly malignant disease, is the most common primary bone tumor
      and is frequently found in children and adolescents. In order to isolate
      antibodies against osteosarcoma antigens, a combinatorial osteosarcoma Fab
      library displayed on the surface of phages was used. After three rounds of
      selection on the surface of tumor cells, several osteosarcoma-reactive Fabs were
      detected. From these Fabs, five were better characterized, and despite having
      differences in their VH (heavy chain variable domain) and Vkappa (kappa chain
      variable domain) regions, they all bound to a protein with the same molecular
      mass. Further analysis by cell ELISA and immunocytochemistry suggested that the
      Fabs recognize a membrane-associated tumor antigen expressed in higher amounts in
      neoplasic cells than in normal tissue. These results suggest that the human Fabs
      selected in this work are a valuable tool for the study of this neoplasia.

PMID- 20037729
TI  - Modelling the survival of Escherichia coli O157:H7 on raw portioned tomatoes,
      inoculated with Aspergillus fumigatus and Emericella nidulans.
AB  - The metabiotic interactions occurring among two fungi (Aspergillus fumigatus and
      Emericella nidulans) and Escherichia coli O157:H7 on raw portioned tomatoes were
      studied. Tomatoes, preinoculated with the moulds and inoculated with the
      pathogen, were packaged in air and stored at 4, 8 and 12( composite function)C
      for 9 days; pathogen cell number and pH were monitored throughout the storage and
      the data were modeled using three different equations (Geeraerd, Weibull, and
      modified Weibull), to assess the shoulder length, the 1-log reduction time, and
      the death time. Both A. fumigatus and E. nidulans increased the survival of E.
      coli O157:H7 through the prolongation of the shoulder length; in contrast, the
      death time was significantly increased. The results of this paper suggested that
      the metabiotic interactions aspergilli/E. coli O 157:H7 could be of public
      concern, as the consumption of tomatoes (or other fruits and vegetables)
      contaminated both by the moulds and the pathogen is a possible scenario.

PMID- 20037730
TI  - A similarity search using molecular topological graphs.
AB  - A molecular similarity measure has been developed using molecular topological
      graphs and atomic partial charges. Two kinds of topological graphs were used. One
      is the ordinary adjacency matrix and the other is a matrix which represents the
      minimum path length between two atoms of the molecule. The ordinary adjacency
      matrix is suitable to compare the local structures of molecules such as
      functional groups, and the other matrix is suitable to compare the global
      structures of molecules. The combination of these two matrices gave a similarity
      measure. This method was applied to in silico drug screening, and the results
      showed that it was effective as a similarity measure.

PMID- 20037731
TI  - Improved method for in vitro secondary amastigogenesis of Trypanosoma cruzi:
      morphometrical and molecular analysis of intermediate developmental forms.
AB  - Trypanosoma cruzi undergoes a biphasic life cycle that consists of four alternate
      developmental stages. In vitro conditions to obtain a synchronic transformation
      and efficient rates of pure intermediate forms (IFs), which are indispensable for
      further biochemical, biological, and molecular studies, have not been reported.
      In the present study, we established an improved method to obtain IFs from
      secondary amastigogenesis. During the transformation kinetics, we observed
      progressive decreases in the size of the parasite body, undulating membrane and
      flagellum that were concomitant with nucleus remodeling and kinetoplast
      displacement. In addition, a gradual reduction in parasite movement and
      acquisition of the amastigote-specific Ssp4 antigen were observed. Therefore, our
      results showed that the in vitro conditions used obtained large quantities of
      highly synchronous and pure IFs that were clearly distinguished by morphometrical
      and molecular analyses. Obtaining these IFs represents the first step towards an
      understanding of the molecular mechanisms involved in amastigogenesis.

PMID- 20037732
TI  - Attenuation of acute lung inflammation and injury by whole body cooling in a rat
      heatstroke model.
AB  - Whole body cooling is the current therapy of choice for heatstroke because the
      therapeutic agents are not available. In this study, we assessed the effects of
      whole body cooling on several indices of acute lung inflammation and injury which
      might occur during heatstroke. Anesthetized rats were randomized into the
      following groups and given (a) no treatment or (b) whole body cooling immediately
      after onset of heatstroke. As compared with the normothermic controls, the
      untreated heatstroke rats had higher levels of pleural exudates volume and
      polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric
      oxide synthase expression, histologic lung injury score, and bronchoalveolar
      proinflammatory cytokines and glutamate, and PaCO2. In contrast, the values of
      mean arterial pressure, heart rate, PaO2, pH, and blood HCO3(-) were all
      significantly lower during heatstroke. The acute lung inflammation and injury and
      electrolyte imbalance that occurred during heatstroke were significantly reduced
      by whole body cooling. In conclusion, we identified heat-induced acute lung
      inflammation and injury and electrolyte imbalance could be ameliorated by whole
      body cooling.

PMID- 20037733
TI  - Factors associated with hepatitis A vaccination receipt in one-year-olds in the
      state of Michigan.
AB  - The objectives of this study were to determine factors associated with hepatitis
      A vaccination and to assess overall hepatitis A vaccination coverage levels among
      one-year-olds in Michigan. The study population was the first hepatitis A
      vaccination-eligible birth cohort (n = 134 226) enrolled in the Michigan Care
      Improvement Registry (MCIR) after 2006 recommendations were made to routinely
      vaccinate all one-year-olds. All children whose first birthday occurred on or
      between May 1, 2006 and April 31, 2007 were included in the study population.
      Racial/ethnic minorities had increased odds of receiving the hepatitis A
      vaccination in Michigan, and Medicaid and WIC status modified this relationship.
      Fully understanding these relationships will be useful in targeting vaccination
      outreach and education programs.

PMID- 20037734
TI  - Toward engineering synthetic microbial metabolism.
AB  - The generation of well-characterized parts and the formulation of biological
      design principles in synthetic biology are laying the foundation for more complex
      and advanced microbial metabolic engineering. Improvements in de novo DNA
      synthesis and codon-optimization alone are already contributing to the
      manufacturing of pathway enzymes with improved or novel function. Further
      development of analytical and computer-aided design tools should accelerate the
      forward engineering of precisely regulated synthetic pathways by providing a
      standard framework for the predictable design of biological systems from well
      characterized parts. In this review we discuss the current state of synthetic
      biology within a four-stage framework (design, modeling, synthesis, analysis) and
      highlight areas requiring further advancement to facilitate true engineering of
      synthetic microbial metabolism.

PMID- 20037736
TI  - Phenotypic transition of the collecting duct epithelium in congenital urinary
      tract obstruction.
AB  - Epithelial-mesenchymal transition (EMT) has emerged in recent years as an
      important process in the development of organ fibrosis in many human diseases.
      Our previous experience in a nonhuman primate model of obstructive nephropathy
      suggested that EMT of collecting duct epithelium contributes to the development
      of interstitial fibrosis. In this study we demonstrate for the first time in
      humans that obstructed fetal collecting duct epithelium undergoes transition to
      mesenchymal phenotype, characterized by decreased expression of epithelial
      markers, de novo expression of mesenchymal markers with subsequent loss of cell
      cell interaction, disruption of the basement membrane, and increased deposition
      of extracellular matrix into the expanded interstitium of the obstructed kidney.
      The results of this study therefore support the previous findings from animal
      studies and suggest that EMT of the collecting duct epithelium might contribute
      to the development of interstitial fibrosis in human fetal obstructive
      nephropathy.

PMID- 20037735
TI  - Progesterone induces scolex evagination of the human parasite Taenia solium:
      evolutionary implications to the host-parasite relationship.
AB  - Taenia solium cysticercosis is a health problem in underdeveloped and developed
      countries. Sex hormones are involved in cysticercosis prevalence in female and
      male pigs. Here, we evaluated the effects of progesterone and its antagonist
      RU486 on scolex evagination, which is the initial step in the development of the
      adult worm. Interestingly, progesterone increased T. solium scolex evagination
      and worm growth, in a concentration-independent pattern. Progesterone effects
      could be mediated by a novel T. solium progesterone receptor (TsPR), since RU486
      inhibits both scolex evagination and worm development induced by progesterone.
      Using RT-PCR and western blot, sequences related to progesterone receptor were
      detected in the parasite. A phylogenetic analysis reveals that TsPR is highly
      related to fish and amphibian progesterone receptors, whereas it has a distant
      relation with birds and mammals. Conclusively, progesterone directly acts upon T.
      solium cysticerci, possibly through its binding to a progesterone receptor
      synthesized by the parasite.

PMID- 20037737
TI  - Reduction of Foxp3+ cells by depletion with the PC61 mAb induces mortality in
      resistant BALB/c mice infected with Toxoplasma gondii.
AB  - Regulatory T cells (Tregs) are CD4(+)Foxp3(+) cells that modulate autoimmune
      responses. Tregs have been shown to be also involved during the immune response
      against infectious agents. The aim of this work is to study the role of Tregs
      during the infection with the intracellular protozoan Toxoplasma gondii.
      Resistant BALB/c mice were injected with 200 microg of anti-CD25 mAb (clone PC61)
      and 2 days later they were infected with 20 cysts of the ME49 strain of T.
      gondii. We observed that depleted mice showed 50-60% mortality during the acute
      infection. When FACS analysis was carried out, we observed that although
      injection of PC61 mAb eliminated 50% of Tregs, infected-depleted mice showed a
      similar percentage of CD25(+)Foxp3(-) (activated T cells, Tact) to those observed
      in infected nondepleted animals, demonstrating that in our depletion/infection
      system, injection of PC61 mAb did not hamper T cell activation while percentage
      of Tregs was reduced by 75% 10 days post infection. We concluded that Tregs are
      essential during protection in the acute phase of T. gondii infection.

PMID- 20037738
TI  - High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal
      stromal cells from whole primitive human umbilical cord tissue.
AB  - Human umbilical cord blood is an excellent primitive source of noncontroversial
      stem cells for treatment of hematologic disorders; meanwhile, new stem cell
      candidates in the umbilical cord (UC) tissue could provide therapeutic cells for
      nonhematologic disorders. We show novel in situ characterization to identify and
      localize a panel of some markers expressed by mesenchymal stromal cells (MSCs;
      CD44, CD105, CD73, CD90) and CD146 in the UC. We describe enzymatic isolation and
      purification methods of different UC cell populations that do not require manual
      separation of the vessels and stroma of the coiled, helical-like UC tissue.
      Unique quantitation of in situ cell frequency and stromal cell counts upon
      harvest illustrate the potential to obtain high numerical yields with these
      methods. UC stromal cells can differentiate to the osteogenic and chondrogenic
      lineages and, under specific culturing conditions, they exhibit high
      expandability with unique long-term stability of their phenotype. The remarkable
      stability of the phenotype represents a novel finding for human MSCs, from any
      source, and supports the use of these cells as highly accessible stromal cells
      for both basic studies and potentially therapeutic applications such as
      allogeneic clinical use for musculoskeletal disorders.

PMID- 20037739
TI  - A novel flow-perfusion bioreactor supports 3D dynamic cell culture.
AB  - BACKGROUND: Bone engineering requires thicker three-dimensional constructs than
      the maximum thickness supported by standard cell-culture techniques (2 mm). A
      flow-perfusion bioreactor was developed to provide chemotransportation to thick
      (6 mm) scaffolds. METHODS: Polyurethane scaffolds, seeded with murine
      preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained
      in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for
      cellular distribution, viability, metabolic activity, and density at the
      periphery and core. RESULTS: By day 8, static scaffolds had a periphery cell
      density of 67% +/- 5.0%, while in the core it was 0.3% +/- 0.3%. Flow-perfused
      scaffolds demonstrated peripheral cell density of 94% +/- 8.3% and core density
      of 76% +/- 3.1% at day 8. CONCLUSIONS: Flow perfusion provides
      chemotransportation to thick scaffolds. This system may permit high throughput
      study of 3D tissues in vitro and enable prefabrication of biological constructs
      large enough to solve clinical problems.

PMID- 20037740
TI  - Association of interleukin-8 with cachexia from patients with low-third gastric
      cancer.
AB  - Background. Interleukin (IL)-8 has been implicated in the development of cancer
      cachexia. The polymorphism of IL-8 gene, which may affect the production level of
      IL-8, may be associated with cancer cachexia. Methods. The serum IL-8 level in
      our study was examined by radioimmunoassay. We also analyzed single nucleotide
      polymorphisms (SNPs) -251 A/T and +781 C/T of IL-8 gene, using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Results. The serum
      levels of IL-8 were significantly elevated in patients with low-third gastric
      cancer compared with controls, and were further up-regulated in patients with
      cachexia than those without (Z = -3.134, P = .002). A significantly increased
      frequency of +781 T allele was noted in patients with cachexia (OR = 2.247, 95%
      CI: 1.351-3.737, P = .002). The +781 TT genotype was observed to be associated
      with a significantly increased risk of cachexia (OR = 3.167, 95% CI: 1.265-7.929,
      P = .011), and with odds ratio of 3.033 (95% CI: 1.065-8.639, P = .038) for
      cachexia after adjusting for potential confounding factors. Meanwhile, haplotype
      analysis indicated a borderline positive association between T(251)T(781)
      haplotype and cachexia as compared with the T(251)C(781) haplotype (OR = 4.92,
      95% CI: 1.00-24.28; ,P = .053). Conclusions. IL-8 appears to be associated with
      cachexia from patients with low-third gastric cancer.

PMID- 20037741
TI  - PPARs in Irradiation-Induced Gastrointestinal Toxicity.
AB  - The use of radiation therapy to treat cancer inevitably involves exposure of
      normal tissues. Although the benefits of this treatment are well established,
      many patients experience distressing complications due to injury to normal
      tissue. These side effects are related to inflammatory processes, and they
      decrease therapeutic benefit by increasing the overall treatment time. Emerging
      evidence indicates that PPARs and their ligands are important in the modulation
      of immune and inflammatory reactions. This paper discusses the effects of
      abdominal irradiation on PPARs, their role and functions in irradiation toxicity,
      and the possibility of using their ligands for radioprotection.

PMID- 20037742
TI  - A neural mass model to simulate different rhythms in a cortical region.
AB  - An original neural mass model of a cortical region has been used to investigate
      the origin of EEG rhythms. The model consists of four interconnected neural
      populations: pyramidal cells, excitatory interneurons and inhibitory interneurons
      with slow and fast synaptic kinetics, GABA(A, slow) and GABA(A,fast)
      respectively. A new aspect, not present in previous versions, consists in the
      inclusion of a self-loop among GABA(A,fast) interneurons. The connectivity
      parameters among neural populations have been changed in order to reproduce
      different EEG rhythms. Moreover, two cortical regions have been connected by
      using different typologies of long range connections. Results show that the model
      of a single cortical region is able to simulate the occurrence of multiple power
      spectral density (PSD) peaks; in particular the new inhibitory loop seems to have
      a critical role in the activation in gamma (gamma) band, in agreement with
      experimental studies. Moreover the effect of different kinds of connections
      between two regions has been investigated, suggesting that long range connections
      toward GABA(A,fast) interneurons have a major impact than connections toward
      pyramidal cells. The model can be of value to gain a deeper insight into
      mechanisms involved in the generation of gamma rhythms and to provide better
      understanding of cortical EEG spectra.

PMID- 20037745
TI  - Highly ordered Pd nanowire array by template fabrication for propanol
      electrooxidation.
AB  - Highly ordered Pd nanowire arrays (NWAs) prepared by electrodeposition method
      using the fresh prepared anodic aluminum oxide (AAO) as the template have been
      characterized by X-ray diffraction pattern (XRD), X-ray photoelectron
      spectroscopy (XPS), transmission electron microscope (TEM), scanning electron
      microscopy (SEM), and electrochemical measurements. SEM results revealed that the
      brush-shaped Pd NWAs are dispersed uniformly. The diameter and length of the
      obtained Pd NWAs are about 50 nm and 850 nm, respectively. Furthermore, the
      electrocatalytic activity of Pd NWAs electrode for propanol oxidation in alkaline
      media has also been studied. It is found that the obtained nanostructurs exhibit
      excellent electrocatalytic activity toward the oxidation of propanol,
      demonstrating the potential application in portable direct alcohol fuel cells
      (DAFCs).

PMID- 20037744
TI  - Serologic investigations in children with inflammatory bowel disease and food
      allergy.
AB  - The aim of the study was the evaluation of frequency and titre of IgA ASCA and
      IgG ASCA and p-ANCA, c-ANCA in children with IBD and occurrence of ASCA
      antibodies in relation to coexistence of FA. Patients and methods. The study
      comprised 95 children at the ages of 2 to 18 years. The diagnosis of IBD was
      established on the basis of Porto criteria. Tests of blood serum were performed
      in all children: IgA and IgG ASCA, p-ANCA, c-ANCA using ELISA method. Results.
      IgE-dependent FA was found in 32.5% children with UC and in 21% with CD. We did
      not observe any relation between the occurrence of FA and the frequency and ASCA
      titre. p-ANCA were significantly more frequent in the group of children with UC.
      The occurrence of ASCA antibodies was observed in 73.7% of children with CD,
      17.5% with UC and almost 30% with allergic colitis. Conclusions. Patients with CD
      and the presence of ASCA revealed a significantly more frequent localization of
      lesions within the small bowel and a tendency towards older age. We observed a
      connection between the occurrence of antibodies and the examined mutations of
      gene NOD2/CARD15.

PMID- 20037746
TI  - A case of active rheumatoid arthritis with renal dysfunction treated effectively
      with tocilizumab monotherapy.

PMID- 20037743
TI  - Targeting the epidermal growth factor receptor in epithelial ovarian cancer:
      current knowledge and future challenges.
AB  - The epidermal growth factor receptor is overexpressed in up to 60% of ovarian
      epithelial malignancies. EGFR regulates complex cellular events due to the large
      number of ligands, dimerization partners, and diverse signaling pathways engaged.
      In ovarian cancer, EGFR activation is associated with increased malignant tumor
      phenotype and poorer patient outcome. However, unlike some other EGFR-positive
      solid tumors, treatment of ovarian tumors with anti-EGFR agents has induced
      minimal response. While the amount of information regarding EGFR-mediated
      signaling is considerable, current data provides little insight for the lack of
      efficacy of anti-EGFR agents in ovarian cancer. More comprehensive, systematic,
      and well-defined approaches are needed to dissect the roles that EGFR plays in
      the complex signaling processes in ovarian cancer as well as to identify
      biomarkers that can accurately predict sensitivity toward EGFR-targeted
      therapeutic agents. This new knowledge could facilitate the development of
      rational combinatorial therapies to sensitize tumor cells toward EGFR-targeted
      therapies.

PMID- 20037747
TI  - Marked effect and steroid-sparing ability of anakinra on a patient with
      refractory adult-onset Still's disease.
AB  - We report a case of refractory adult-onset Still's disease (AOSD) successfully
      controlled with anakinra, an interleukin-1 (IL-1) receptor antagonist. The
      patient was a 23-year-old Japanese woman with AOSD who could not be induced into
      remission despite of two courses of pulsed methylprednisolone followed by high
      dose glucocorticoid administration in conjunction with high-dose intravenously
      administered gamma-globulin and methotrexate. To the best of our knowledge, this
      is the first case report in Japan of AOSD remission induced with anakinra.

PMID- 20037748
TI  - Genetic variation and conservation assessment of Chinese populations of Magnolia
      cathcartii (Magnoliaceae), a rare evergreen tree from the South-Central China
      hotspot in the Eastern Himalayas.
AB  - Nine natural populations of the rare evergreen tree Magnolia cathcartii
      (Magnoliaceae) were sampled across its natural range, and amplified fragment
      length polymorphism (AFLP) markers were used to assess genetic variation within
      and among populations. Three ex situ populations were also surveyed to determine
      whether conservation plantings include the entire genetic diversity of the
      species. Genetic diversity within the natural populations was very low (0.122 for
      Nei's gene diversity), and the southeast populations had the highest diversity.
      The ex situ populations had a lower diversity than the mean diversity for all
      populations, and none of the ex situ populations reached the levels of diversity
      found in their source populations. Genetic differentiation was high among natural
      populations (G st = 0.247), and an isolation-by-distance pattern was detected.
      Habitat fragmentation, restricted gene flow, and geitonogamy are proposed to be
      the primary reasons for the low genetic diversity and high genetic
      differentiation. More protection is needed, especially for the southeast
      populations, which possess the highest numbers of unique alleles according to
      AFLP fragment analyses. The ex situ program was a good first step towards
      preserving this species, but the current ex situ populations preserve only a
      limited portion of its genetic diversity. Future ex situ efforts should focus on
      enhancing the plantings with individuals from southeastern Yunnan.

PMID- 20037749
TI  - Outcomes of matched sibling and alternative donor stem cell transplantation for
      26 children with severe aplastic anemia.
AB  - In this study, we reported the outcomes of hematopoietic stem cell
      transplantation (HSCT) as a treatment modality for pediatric patients admitted
      over the past 20 years in a single institute. From January 1989 to January 2007,
      26 patients with a median age of 8 years underwent 14 matched sibling donor (MSD)
      and 12 alternative donor (AD) transplantations. Two patients received second
      transplantation successfully after primary graft failure and late graft
      rejection. Two patients who received transplantation from matched unrelated
      donors (MUD) died of sepsis, and one of them also had a graft failure at death.
      The overall 5-year survival rate was 92.1%: 83.3% for AD transplantation and 100%
      for MSD transplantation. Grade II acute graft versus host disease (GVHD)
      developed in 3 patients, and extensive chronic GVHD developed in 2 patients. An
      interval of more than 6 months from diagnosis to transplantation was the major
      poor prognostic factor for our patients' survival. Thus, in our experience, HSCT
      from a MSD remains the first choice of treatment for pediatric patients with
      severe aplastic anemia. For patients without MSD, transplantation from an AD can
      also result in long-term survival. Earlier transplantation after diagnosis can
      also result in better outcomes.

PMID- 20037751
TI  - Overshoot phenomenon of oxygen uptake during recovery from maximal exercise in
      patients with previous myocardial infarction.
AB  - The overshoot in oxygen uptake (VO2 overshoot) during recovery from maximal
      exercise is thought to reflect an overshoot in cardiac output. We investigated
      whether this phenomenon is related to cardiopulmonary function during exercise in
      cardiac patients. A total of 201 consecutive patients with previous myocardial
      infarction underwent cardiopulmonary exercise testing (CPX). An apparent VO2
      overshoot during the recovery from CPX (6.5+/-8.1% increase relative to the peak
      VO2) was observed in ten patients. A comparison of patients with the VO2
      overshoot to those without the VO2 overshoot revealed that the former had a
      significantly lower left ventricular ejection fraction (40.1+/-19.1 vs. 55. 2+/
      14.9%, respectively, p = 0.002) and larger left ventricular diastolic and
      systolic dimensions. Patients with the VO2 overshoot also had a significantly
      lower peak VO2 (13.1+/-6.1 vs. 18.1+/-4.5 ml/min/kg, p < 0.001), lower
      DeltaVO2/DeltaWR (work rate) (6.6+/-3.8 vs. 9.5+/-1.7 mL/min/W, p < 0.0001), and
      a higher E (minute ventilation)/VCO2 (carbon dioxide output) slope (45.0+/-18.6
      vs. 32.6+/-6.6, p < 0.0001) than those without the overshoot. A VO2 overshoot
      during recovery from maximal exercise was found in 5% of patients with previous
      myocardial infarction. This condition, which suggests a transient mismatch
      between cardiac contractility and afterload reduction, was found to be related to
      impaired cardiopulmonary function during exercise.

PMID- 20037750
TI  - Methylation status of nine tumor suppressor genes in multiple myeloma.
AB  - Aberrant methylation in promoter-associated CpG islands has been recognized as a
      major mechanism for tumor suppressor gene silencing in several malignancies. We
      determined the methylation status of nine tumor suppressor genes in 68 newly
      diagnosed MM patients by methylation-specific PCR. The frequency of promoter
      hypermethylation for individual genes was: CDH1, 50%; p16 INK4a, 42.8%; p15
      INK4b, 16.2%; SHP1, 14.7%; ER and BNIP3, 13.2%; RAR beta, 11.8%; DAPK 5.9%; and
      MGMT 0%. Overall, 79% of patients presented at least one hypermethylated gene. By
      univariate analysis, hypermethylation of DAPK (P < 0.001) and RAR beta (P = 0.01)
      genes were identified as adverse prognostic features. Median OS of patients with
      hypermethylation in DAPK (4 months) and RAR beta (34 months) was significantly
      lower than in patients without hypermethylation (median survival not reached),
      with values of P < 0.001 and P = 0.01, respectively. Our data suggest that DAPK
      and RAR beta hypermethylation are adverse prognostic factors in MM. The relevance
      of these findings as poor prognosis indicators requires confirmation in a larger
      sample with longer follow-ups.

PMID- 20037756
TI  - Mutations in the K(+)-channel KcsA toward Kir channels alter salt-induced
      clusterization and blockade by quaternary alkylammonium ions.
AB  - Protein aggregation is a result of malfunction in protein folding, assembly, and
      transport, caused by protein mutation and/or changes in the cell environment,
      thus triggering many human diseases. We have shown that bacterial K(+)-channel
      KcsA, which acts as a representative model for ion channels, forms salt-induced
      large conductive complexes in a particular environment. In the present study, we
      investigated the effects of point mutations in the selectivity filter of KcsA on
      intrinsic stability, aggregation, and channel blocking behavior. First, we found
      that a low sodium chloride concentration in potassium-containing media induced
      fast transfer of single channels to a planar lipid bilayer. Second, increasing
      the sodium chloride concentration drastically increased the total channel
      current, indicating enhanced vesicle fusion and transfer of multiple channels to
      a planar lipid bilayer. However, such complexes exhibited high conductance as
      well as higher open probability compared to the unmodified KcsA behavior shown
      previously. Interestingly, the affinity of aggregated complexes for larger
      symmetric quaternary alkylammonium ions (QAs) was found to be much higher than
      that for tetraethylammonium, a classical blocker of the K(+) channel. Based on
      these findings, we propose that mutant channel complexes exhibit larger pore
      dimensions, thus resembling more the topological properties of voltage-gated and
      inwardly rectifying K(+) channels.

PMID- 20037757
TI  - The chicken Z chromosome is enriched for genes with preferential expression in
      ovarian somatic cells.
AB  - Theory predicts that sexually antagonistic mutations will be over- or under
      represented on the X and Z chromosomes, depending on their average dominance
      coefficients. However, as little is known about the dominance coefficients for
      new mutations, the effect of sexually antagonistic selection is difficult to
      predict. To elucidate the role of sexually antagonistic selection in the
      evolution of Z chromosome gene content in chicken, we analyzed publicly available
      microarray data from several somatic tissues as well as somatic and germ cells of
      the ovary. We found that the Z chromosome is enriched for genes showing
      preferential expression in ovarian somatic cells, but not for genes with
      preferential expression in primary oocytes or non-sex-specific somatic tissues.
      Our results suggest that sexual antagonism leads to a higher abundance of female
      benefit alleles on the Z chromosome. No bias toward Z-linkage for oocyte-enriched
      genes can be explained by lower intensity of sexually antagonistic selection in
      ovarian germ cells compared to ovarian somatic cells. An alternative explanation
      would be that meiotic Z chromosome inactivation hinders accumulation of oocyte
      expressed genes on the Z chromosome. Our results are consistent with findings in
      mammals and indicate that recessive rather than dominant sexually antagonistic
      mutations shape the gene content of the X and Z chromosomes.

PMID- 20037758
TI  - Safety, efficacy and pharmacokinetics of S-1 in a hemodialysis patient with
      advanced gastric cancer.
AB  - PURPOSE: The safety and efficacy of S-1 in hemodialysis patients have not been
      established. We evaluated the safety and efficacy and pharmacokinetics of S-1 in
      a hemodialysis patient with advanced gastric cancer. PATIENT: A 66-year-old
      Japanese man with chronic renal failure, who had undergone hemodialysis three
      times a week for 3 years. Based on the diagnosis of stage IV gastric cancer, S-1
      therapy was started. S-1 was administered 11 times at a daily dose of 23.5
      mg/m(2) (40 mg/body)after hemodialysis, followed by a rest. One course was a
      period of 28 days. Blood samples were obtained after the first administration of
      S-1 and before beginning the fourth course. The concentration of 5-FU was
      determined by high-performance liquid chromatography. RESULTS: Area under the
      concentration-time curve (AUC)of 5-FU was 2647.2 ng h/mL after administration of
      S-1 of 23.5 mg/m(2) (40 mg/body). During the S-1 treatment,serious adverse events
      such as neutropenia were not observed; however, decreases in hemoglobin level
      were observed (grade 3). The treatment was well tolerated. After the second
      course of chemotherapy, the primary lesion showed a partial response and lymph
      node metastases and liver metastases showed stable disease. CONCLUSIONS: Our
      results suggest that S-1 is an important treatment option for patients with
      hemodialysis with advanced gastric cancer.

PMID- 20037759
TI  - Analyzing and reconstructing reticulation networks under timing constraints.
AB  - Reticulation networks are now frequently used to model the history of life for
      various groups of species whose evolutionary past is likely to include
      reticulation events such as horizontal gene transfer or hybridization. However,
      the reconstructed networks are rarely guaranteed to be temporal. If a
      reticulation network is temporal, then it satisfies the two biologically
      motivated timing constraints of instantaneously occurring reticulation events and
      successively occurring speciation events. On the other hand, if a reticulation
      network is not temporal, it is always possible to make it temporal by adding a
      number of additional unsampled or extinct taxa. In the first half of the paper,
      we show that deciding whether a given number of additional taxa is sufficient to
      transform a non-temporal reticulation network into a temporal one is an NP
      complete problem. As one is often given a set of gene trees instead of a network
      in the context of hybridization, this motivates the second half of the paper
      which provides an algorithm, called TemporalHybrid, for reconstructing a temporal
      hybridization network that simultaneously explains the ancestral history of two
      trees or indicates that no such network exists. We further derive two methods to
      decide whether or not a temporal hybridization network exists for two given trees
      and illustrate one of the methods on a grass data set.

PMID- 20037760
TI  - Traveling wave solutions from microscopic to macroscopic chemotaxis models.
AB  - In this paper, we study the existence and nonexistence of traveling wave
      solutions for the one-dimensional microscopic and macroscopic chemotaxis models.
      The microscopic model is based on the velocity jump process of Othmer et al.
      (SIAM J Appl Math 57:1044-1081, 1997). The macroscopic model, which can be shown
      to be the parabolic limit of the microscopic model, is the classical Keller-Segel
      model, (Keller and Segel in J Theor Biol 30:225-234; 377-380, 1971). In both
      models, the chemosensitivity function is given by the derivative of a potential
      function, Phi(v), which must be unbounded below at some point for the existence
      of traveling wave solutions. Thus, we consider two examples: Phi(v) = ln V and
      Phi(v) = ln[v/(1 - v)]. The mathematical problem reduces to proving the existence
      or nonexistence of solutions to a nonlinear boundary value problem with variable
      coefficient on R. The main purpose of this paper is to identify the relationships
      between the two models through their traveling waves, from which we can observe
      how information are lost, retained, or created during the transition from the
      microscopic model to the macroscopic model. Moreover, the underlying biological
      implications of our results are discussed.

PMID- 20037761
TI  - alpha-Synuclein pathology in the spinal cord autonomic nuclei associates with
      alpha-synuclein pathology in the brain: a population-based Vantaa 85+ study.
AB  - In most subjects with Parkinson's disease and dementia with Lewy bodies, alpha
      synuclein (alphaS) immunoreactive pathology is found not only in the brain but
      also in the autonomic nuclei of the spinal cord. However, neither has the
      temporal course of alphaS pathology in the spinal cord in relation to the brain
      progression been established, nor has the extent of alphaS pathology in the
      spinal cord been analyzed in population-based studies. Using
      immunohistochemistry, the frequency and distribution of alphaS pathology were
      assessed semiquantitatively in the brains and spinal cord nuclei of 304 subjects
      who were aged at least 85 in the population-based Vantaa 85+ study. alphaS
      pathology was common in the spinal cord; 102 (34%) subjects had classic alphaS
      pathology in the thoracic and/or sacral autonomic nuclei. Moreover, 134 (44%)
      subjects showed grain- or dot-like immunoreactivity in neuropil (mini-aggregates)
      without classic Lewy neurites or Lewy bodies (LBs). The latter type of alphaS
      accumulation is associated with age, but also the classic alphaS pathology was
      found more often in the oldest compared to the youngest age group. The severity
      of alphaS pathology in the spinal cord autonomic nuclei is significantly
      associated with the extent and severity of alphaS pathology in the brain. Of the
      subjects, 60% with moderate to severe thoracic alphaS pathology and up to 89%
      with moderate to severe sacral alphaS pathology had diffuse neocortical type of
      LB pathology in the brain. alphaS pathology exclusively in the spinal cord was
      rare. Our study indicates that in general alphaS pathology in the spinal cord
      autonomic nuclei is associated with similar pathology in the brain.

PMID- 20037762
TI  - Sildenafil improves scotoma after posterior cerebral infarctions: a case report.
AB  - A 65-year-old man had an embolic stroke of both posterior cerebral arteries in
      2002. Two years later he noted rapid improvement of the residual bilateral
      inferior quadrant anopia whenever he took 25 mg sildenafil. The improvement of
      scotomas was verified by visual field examinations and persisted reproducibly for
      3-7 days. An overlay of a subtraction of functional magnetic resonance imaging
      (MRI) during visual stimulation before and after medication onto a T1-weighted
      MRI of the patient revealed additional activations along the margins of the old
      cerebral infarctions. These findings and the additional results of a perfusion
      MRI suggest that phosphodiesterase 5 inhibitors may prove beneficial in the
      rehabilitative course after ischemic strokes.

PMID- 20037763
TI  - Epilepsy during the Middle Ages, the Renaissance   and the Enlightenment.
AB  - The purpose of this study was to pinpoint the views on epilepsy as a disease and
      symptom during medieval times and the Renaissance. A thorough study of texts,
      medical books and reports along with a review of the available literature in
      PubMed was undertaken. With the exception of some early Byzantine doctors in the
      East and some of the representatives of Arab medicine, scientific views and
      observations on epilepsy in the West were overrun by the domination of the
      Catholic Church. This led to the formulation of superstitious views of the
      disease; epileptics were considered possessed and, therefore, only religious
      methods could possibly cure it. Near the end of the fourteenth century,
      physicians were emancipated from Catholic intervention. The Renaissance is marked
      by a plethora of new treatises on epilepsy regarding the mechanisms of epileptic
      convulsions, the connection with various clinical conditions such as tumors and
      venereal diseases and the collection of interesting cases.

PMID- 20037764
TI  - Cerebral vasomotor reactivity in epilepsy patients.
AB  - Vasomotor reactivity, which can be defined as the cerebral vasculature response
      to hypoxia, is not well known in epilepsy patients. We aimed to evaluate
      cerebrovascular reserve in idiopathic generalized epilepsy patients using
      transcranial Doppler ultrasonography (TCD). The study included 20 patients and 20
      healthy volunteers. Diagnosis of epilepsy was based on the observation of seizure
      in the video electroencephalography unit. Cerebrovascular reactivity was
      evaluated by means of the breath-holding index. Insonation depth and basal
      velocity were symmetrical and not significantly different between the two groups
      (p[0.05). The breath-holding index ranged from 0.62 to 4.45 (mean 2.13 +/- 0.83)
      in the epilepsy patients and 0.57 to 2.55 (mean 1.60 +/- 0.46) in the control
      group (p?0.05). Breath-holding index values showed that cerebrovascular reserve
      in epilepsy patients was increased, as compared to healthy individuals.
      Cerebrovascular reserve was increased in epilepsy patients; this should not be
      accepted as an abnormality, but might have been the result of an adaptive
      mechanism that protects the brain from hypoxic challenges due to seizure apnea.

PMID- 20037765
TI  - Primary central nervous system vasculitis and moyamoya disease: similarities and
      differences.
AB  - Primary central nervous system vasculitis (PCNSV) and moyamoya disease (MMD)
      represent rare and poorly-understood causes of stroke. Both may present with
      similar clinical and auxiliary findings, but differentiation is extremely
      important because they require different treatment regimens. Our cohort included
      21 white patients with PCNSV and 21 white patients with MMD. Clinical and
      diagnostic features were obtained by retrospective chart review; follow-up
      information and outcome were obtained prospectively. Data were compared between
      patients with PCNSV and MMD using Chi square test or Fisher's exact test for
      categorical data and Mann-Whitney U test for continuous data. The mean age at
      symptom onset was 42.48 years in PCNSV and 31.0 years in MMD (p = 0.008). All
      patients with MMD presented with ischemic events while cerebral ischemia was
      observed in only 14 of 21 patients (66.7%) with PCNSV (p = 0.004). There was no
      significant difference regarding the frequency of headaches, which represented an
      important symptom in both conditions. Conventional cerebral angiography verified
      correct diagnosis in 13 of 17 patients (76.5%) with PCNSV while angiogram
      verified correct diagnosis in all patients with MMD (p = 0.032). MRI and
      cerebrospinal fluid studies were appropriate to differentiate between the
      inflammatory and the non-inflammatory disease. Three PCNSV patients and two MMD
      patients died within documented follow-up. Despite important pathophysiological
      and angiographic differences, PCNSV and MMD may present with similar clinical and
      auxiliary findings. An intensive workup including MRI, conventional cerebral
      angiography and CSF studies is required to avoid misdiagnosis.

PMID- 20037766
TI  - Cue-switch costs in task-switching: cue priming or control processes?
AB  - In the explicitly cued task-switching paradigm, two cues per task allow
      separation of costs associated with switching cues from costs of switching tasks.
      Whilst task-switch costs have become controversial, cue-switch costs are robust.
      The processes that contribute to cue-switch costs are under-specified in the
      literature: they could reflect perceptual priming of cue properties, or priming
      of control processes that form relevant working memory (WM) representations of
      task demands. Across two experiments we manipulated cue-transparency in an
      attention-switching design to test the contrasting hypotheses of cue-switch
      costs, and show that such costs emerge from control processes of establishing
      relevant WM representations, rather than perceptual priming of the cue itself.
      When the cues were maximally transparent, cue-switch costs were eradicated. We
      discuss the results in terms of recent theories of cue encoding, and provide a
      formal definition of cue-transparency in switching designs and its relation to WM
      representations that guide task performance.

PMID- 20037767
TI  - Molecular prediction of oseltamivir efficiency against probable influenza A (H1N1
      2009) mutants: molecular modeling approach.
AB  - To predict the susceptibility of the probable 2009 influenza A (H1N1-2009) mutant
      strains to oseltamivir, MD/LIE approach was applied to oseltamivir complexed with
      the most frequent drug-resistant strains of neuraminidase subtypes N1 and N2: two
      mutations on the framework residues (N294S and H274Y) and the two others on the
      direct-binding residues (E119V and R292K) of oseltamivir. Relative to those of
      the wild type (WT), loss of drug-target interaction energies, especially in terms
      of electrostatic contributions and hydrogen bonds were dominantly established in
      the E119V and R292K mutated systems. The inhibitory potencies of oseltamivir
      towards the WT and mutants were predicted according to the ordering of binding
      free energies: WT (-12.3 kcal mol(-1)) > N294S (-10.4 kcal mol(-1)) > H274Y (-9.8
      kcal mol(-1)) > E119 V (-9.3 kcal mol(-1)) > R292K (-7.7 kcal mol(-1)),
      suggesting that the H1N1-2009 influenza with R292K substitution, perhaps,
      conferred a high level of oseltamivir resistance, while the other mutants
      revealed moderate resistance levels. This result calls for an urgent need to
      develop new potent anti-influenza agents against the next pandemic of potentially
      higher oseltamivir-resistant H1N1-2009 influenza.

PMID- 20037768
TI  - Substituting inpatient for outpatient care: what is the impact on hospital costs
      and efficiency?
AB  - Substitution of inpatient for outpatient care is seen as a means to increase
      patient throughput and control costs. The purpose of this study was to assess the
      impact of increased outpatient care on hospital costs and efficiency using
      Finnish specialty-level data from years 2003-2006 to which we applied stochastic
      frontier analysis. The results reveal that outpatient services have a smaller
      impact on total costs than inpatient services. At the same time, increased
      outpatient activity appears to have an adverse effect on estimated cost
      efficiency. This counterintuitive finding is probably due to the low weight given
      to outpatient activities by the Diagnosis Related Groups (DRG) system. A common
      weighting for inpatient and outpatient services is required in order to assess
      accurately the impact of outpatient care on efficiency.

PMID- 20037769
TI  - Topological optimization in hip prosthesis design.
AB  - With particular interest on total hip arthroplasty (THA), optimization of
      orthopedic prostheses is employed in this work to minimize the probability of
      implant failure or maximize prosthesis reliability. This goal is often identified
      with the reduction of stress concentrations at the interface between bone and
      these devices. However, aseptic loosening of the implant is mainly influenced by
      bone resorption phenomena revealed in some regions of the femur when a prosthesis
      is introduced. As a consequence, bone resorption appears due to stress shielding,
      that is to say the decrease of the stress level in the implanted femur caused by
      the significant load carrying of the prosthesis due to its higher stiffness. A
      maximum stiffness topological optimization-based (TO) strategy is utilized for
      non-linear static finite element (FE) analyses of the femur-implant assembly,
      with the goal of reducing stress shielding in the femur and to furnish guidelines
      for re-designing hip prostheses. This is accomplished by employing an extreme
      accuracy for both the three- dimensional reconstruction of the femur geometry and
      the material properties maps assigned as explicit functions of the local
      densities.

PMID- 20037770
TI  - Antimicrobial compounds produced by Lactobacillus sakei subsp.  sakei 2a, a
      bacteriocinogenic strain isolated from a Brazilian meat  product.
AB  - Bacteriocins produced by lactic acid bacteria are gaining increased importance
      due to their activity against undesirable microorganisms in foods. In this study,
      a concentrated acid extract of a culture of Lactobacillus sakei subsp. sakei 2a,
      a bacteriocinogenic strain isolated from a Brazilian pork product, was purified
      by cation exchange and reversed-phase chromatographic methods. The amino acid
      sequences of the active antimicrobial compounds determined by Edman degradation
      were compared to known protein sequences using the BLAST-P software. Three
      different antimicrobial compounds were obtained, P1, P2 and P3, and mass
      spectrometry indicated molecular masses of 4.4, 6.8 and 9.5 kDa, respectively. P1
      corresponds to classical sakacin P, P2 is identical to the 30S ribosomal protein
      S21 of L. sakei subsp. sakei 23 K, and P3 is identical to a histone-like DNA
      binding protein HV produced by L. sakei subsp. sakei 23 K. Total genomic DNA was
      extracted and used as target DNA for PCR amplification of the genes sak, lis and
      his involved in the synthesis of P1, P2 and P3. The fragments were cloned in
      pET28b expression vector and the resulting plasmids transformed in E. coli KRX
      competent cells. The transformants were active against Listeria monocytogenes,
      indicating that the activity of the classical sakacin P produced by L. sakei 2a
      can be complemented by other antimicrobial proteins.

PMID- 20037771
TI  - Synthesis and characterization of a new dimethacrylate monomer  based on 5,50
      bis(4-hydroxylphenyl)-hexahydro-4,7-methanoindan  for root canal sealer
      application.
AB  - In this study, a new dimethacrylate monomer 5,5'-bis[4-(2'-hydroxy-3'
      methacryloyloxy-propoxy)-phenyl]-hexahydro-4,7-methan-oindan (5,5'-BHMPHM) with
      molecular weight of 640 and large molecular volume was designed and synthesized.
      The structure of monomer 5,5'-BHMPHM was confirmed by FT-IR, 1H-NMR and elemental
      analysis. Degree of double bond conversion, volume shrinkage, contact angle,
      water sorption and solubility, diffusion coefficient value, flexure strength and
      modulus of 5,5'-BHMPHM/tri(ethylene glycol) dimethacrylate (TEGDMA) based resin
      were measured. 2,2-bis[4-(2'-hydroxy-3'-methacryloyloxy-propoxy)-phenyl]
      propane(Bis-GMA)/TEGDMA based resin was used as reference. The result illustrated
      that the double bond conversion, polymerization shrinkage, and diffusion
      coefficient value of 5,5'-BHMPHM/TEGDMA based resin were significantly lower than
      that of Bis-GMA/TEGDMA based resin (P<0.05). Water sorption, solubility, flexure
      strength and modulus of 5,5'-BHMPHM/TEGDMA based resin were higher than that of
      Bis-GMA/TEGDMA based resin (P<0.05). There was no statistical difference between
      5,5'-BHMPHM/TEGDMA based resin and Bis-GMA/TEGDMA based resin in contact angle
      (P>0.05).

PMID- 20037772
TI  - Nanoscale definition of substrate materials to direct human adult stem cells
      towards tissue specific populations.
AB  - The development of homogenously nano-patterned chemically modified surfaces that
      can be used to initiate a cellular response, particularly stem cell
      differentiation, in a highly controlled manner without the need for exogenous
      biological factors has never been reported, due to that fact that precisely
      defined and reproducible systems have not been available that can be used to
      study cell/material interactions and unlock the potential of a material driven
      cell response. Until now material driven stem cell (furthermore any cell)
      responses have been variable due to the limitations in definition and
      reproducibility of the underlying substrate and the lack of true homogeneity of
      modifications that can dictate a cellular response at a sub-micron level that can
      effectively control initial cell interactions of all cells that contact the
      surface. Here we report the successful design and use of homogenously molecularly
      nanopatterned surfaces to control initial stem cell adhesion and hence function.
      The highly specified nano-patterned arrays were compared directly to silane
      modified bulk coated substrates that have previously been proven to initiate
      mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of
      this study was to prove the efficiency of these previously observed cell
      responses could be enhanced by the incorporation of nano-patterns. Nano-patterned
      surfaces were prepared by Dip Pen Nanolithography (DPN) to produce arrays of 70
      nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal
      functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell
      growth. These nanopatterned surfaces exhibited unprecedented control of initial
      cell interactions and will change the capabilities for stem cell definition in
      vitro and then cell based medical therapies. In addition to highlighting the
      ability of the materials to control stem cell functionality on an unprecedented
      scale this research also introduces the successful scale-up of DPN and the novel
      chemistries and systems to facilitate the production of homogeneously patterned
      substrates (5 mm2) that are applicable for use in in vitro cell conditions over
      prolonged periods for complete control of material driven cell responses.

PMID- 20037773
TI  - Mechanical properties of hydroxyapatite-zirconia compacts  sintered by two
      different sintering methods.
AB  - Microwave sintering is traditionally employed to reduce the sintering temperature
      required to densify powder compacts. The effect of microwave heating on
      hydroxyapatite (HA)-zirconia (ZrO2) green bodies has been investigated in order
      to understand how microwave energy may affect the physical and mechanical
      properties of the resultant densified composites. Laboratory synthesised nano
      sized HA and a commercial nano-sized ZrO2 powder have been ball milled to create
      mixtures containing 0-5 wt% ZrO2 loadings. Compacts were microwave sintered at
      either 700, 1000 or 1200 degrees C with a 1 h hold time. Comparative firings were
      also performed in a resistive element furnace using the same heating profile in
      order to assess the differences between conventional and microwave heating on the
      physical, mechanical and microstructural properties of the composites. Samples
      sintered at 700 degrees C show little sign of densification with open porosities
      of approximately 50%. Composites conventionally sintered at 1000 degrees C were
      between 65 and 75% dense, whereas the samples microwave sintered at this
      temperature were between 55 and 65% dense. Samples sintered at 1200 degreesbC
      showed the greatest degree of densification (>80%) with a corresponding reduction
      in open porosities. TCP generation occurred as a consequence of sintering at 1200
      degrees C, even with 0 wt% ZrO2, and increased degradation of the HA phase to
      form significant amounts of TCP occurred with increasing additions of ZrO2, along
      with increasing open porosity. Nanosized ZrO2 prevents the densification of the
      HA matrix by effectively pinning grain boundaries and this effect is more
      pronounced in the MS materials. Similar strengths are achieved between the
      microwave and conventionally sintered samples. Greater amount of open porosity
      and pore interconnectivity are seen in the MS samples, which are considered to be
      useful for biomedical applications as they can promote osteo-integration.

PMID- 20037774
TI  - Tissue differentiation in an in vivo bioreactor: in silico investigations of
      scaffold stiffness.
AB  - Scaffold design remains a main challenge in tissue engineering due to the large
      number of requirements that need to be met in order to create functional tissues
      in vivo. Computer simulations of tissue differentiation within scaffolds could
      serve as a powerful tool in elucidating the design requirements for scaffolds in
      tissue engineering. In this study, a lattice-based model of a 3D porous scaffold
      construct derived from micro CT and a mechano-biological simulation of a bone
      chamber experiment were combined to investigate the effect of scaffold stiffness
      on tissue differentiation inside the chamber. The results indicate that higher
      scaffold stiffness, holding pore structure constant, enhances bone formation.
      This study demonstrates that a lattice approach is very suitable for modelling
      scaffolds in mechano-biological simulations, since it can accurately represent
      the micro-porous geometries of scaffolds in a 3D environment and reduce
      computational costs at the same time.

PMID- 20037775
TI  - Design of novel 3D gene activated PEG scaffolds with ordered pore structure.
AB  - The ability to genetically modify cells seeded inside synthetic hydrogel
      scaffolds offers a suitable approach to induce and control tissue repair and
      regeneration guiding cell fate. In fact the transfected cells can act as local in
      vivo bioreactor, secreting plasmid encoded proteins that augment tissue
      regeneration processes. We have realized a DNA bioactivated high porous
      poly(ethylene glycol) (PEG) matrix by polyethyleneimine (PEI)/DNA complexes
      adsorption. As the design of the microarchitectural features of a scaffold also
      contributes to promote and influence cell fate, we appropriately designed the
      inner structure of gene activated PEG hydrogels by gelatine microparticles
      templating. Microarchitectural properties of the scaffold were analysed by
      scanning electron microscopy. 3D cell migration and transfection were monitored
      through time-lapse videomicroscopy and confocal laser scanning microscopy.

PMID- 20037776
TI  - FGF2-adsorbed macroporous hydroxyapatite bone granules  stimulate in vitro
      osteoblastic gene expression and differentiation.
AB  - Hydroxyapatite bone granules with a macroporous structure were produced and then
      adsorbed with basic fibroblast growth factor (FGF2). The in vitro scaffolding
      role of the granules in cell population and osteogenic differentiation was
      investigated. The FGF2-adsorbed porous granules allowed the MC3T3-E1 cells to
      adhere well and then proliferate actively. While the cell growth level on the
      FGF2-treated granules was observed to be similar to that on the untreated
      granules, the expression of genes associated with bone, including collagen type
      I, alkaline phosphatase, and osteocalcin was significantly upregulated by the
      FGF2 treatment, particularly at the early stage. Moreover, the production of
      alkaline phosphatase with prolonged culturing was greatly enhanced on the FGF2
      adsorbed granules. Taken together, the FGF2 treatment of the hydroxyapatite
      granules was effective in the osteogenic development and the FGF2-adsorbed bone
      granules may be useful in bone regeneration area.

PMID- 20037777
TI  - The antimicrobial effect of open-cell silver foams.
AB  - Open-cell silver foams with various pore sizes (494, 337, 126 and 39 microm) and
      porosity (60, 70 and 80 vol%) were produced using a powder-based replication
      method. It was found that the foams have strong microbial reduction efficiency.
      The antimicrobial effect of the foams is much stronger on gram-negative bacterium
      (Escherichia coli) than gram-positive bacterium (Staphylococcus aureus). With
      equivalent volume addition of NaCl particles, higher antimicrobial effect was
      found for Ag foams with larger pore size. The difference on antimicrobial effect
      between silver foams with various pore sizes is smaller when porosity of the
      foams increases from 60 to 80%. No correlation between particle sizes of NaCl and
      bacterial growth inhibition was found. In addition, effect of particle sizes and
      pore sizes of the foams on the bacterial growth inhibition is not as much as the
      effect of particle addition. It is expected that the positively charged Ag ions
      released from the surface of Ag foam structure would alter the morphology of
      bacteria strains in which disruption of cell wall and eventually damage were
      implemented.

PMID- 20037778
TI  - UHRF1 inhibits MDR1 gene transcription and sensitizes breast cancer cells to
      anticancer drugs.
AB  - Overexpression of MDR1 in breast cancer remains a major cause for the failure of
      chemotherapy. In the present report, we find UHRF1 plays an important role in
      inhibiting MDR1 promoter activity by directly binding to the MDR1 promoter.
      Knockdown of UHRF1 activates MDR1 promoter activity and expression, attenuates
      the binding of UHRF1 and HDAC1 to the MDR1 promoter.Overexpression of UHRF1 in
      NCI/ADR-RES cells can induce deacetylation of histones H3 and H4 on the MDR1
      promoter, which is facilitated by recruitment of HDAC1 to the MDR1 promoter. Loss
      of histone acetylation is accompanied by loss of binding of the key transcription
      factor, MyoD, CBP and p300, locking in marked suppression of MDR1, increasing
      sensitivity of MDR cancer cells to cytotoxic drugs that are transported by P
      glycoprotein(P-gp). The inhibition of MDR1 expression by UHRF1 may provide
      potential ways to overcome multidrug resistance (MDR) in breast cancer treatment.

PMID- 20037779
TI  - Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast
      cancer.
AB  - Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly
      paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the
      adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes
      predictive of prognosis and paclitaxel response in this trial. Two molecular
      subtype classifications based on conventional immunohistochemical and fluorescent
      in situ hybridization determinations were used: #1: Four groups segregated
      according to the combination of hormone receptor (HR) and HER2 status; #2:
      Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and
      Luminal A). RESULTS: Both subtype classifications yielded prognostic and
      predictive information. HR +/HER2- patients (and Luminal A patients) had a
      significantly better outcome than the other subgroups of patients. The
      superiority of FEC-P over FEC was clearly more marked in HR-/HER2- patients (TN
      patients), particularly in the subset with basal phenotype (TN and either EGFR+
      or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit
      with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better
      response to treatment with FEC-P. Luminal A patients had the best prognosis and
      also have a better outcome with weekly paclitaxel.

PMID- 20037781
TI  - InfoSyll: a syllabary providing statistical information on phonological and
      orthographic syllables.
AB  - There is now a growing body of evidence in various languages supporting the claim
      that syllables are functional units of visual word processing. In the perspective
      of modeling the processing of polysyllabic words and the activation of syllables,
      current studies investigate syllabic effects with subtle manipulations. We
      present here a syllabary of the French language aiming at answering new
      constraints when designing experiments on the syllable issue. The InfoSyll
      syllabary provides exhaustive characteristics and statistical information for
      each phonological syllable (e.g., /fi/) and for its corresponding orthographic
      syllables (e.g., fi, phi, phy, fee, fix, fis). Variables such as the type and
      token positional frequencies, the number and frequencies of the correspondences
      between orthographic and phonological syllables are provided. As discussed, such
      computations should allow precise controls, manipulations and quantitative
      descriptions of syllabic variables in the field of psycholinguistic research.

PMID- 20037782
TI  - Detection of genotoxicity of water from an urbanized stream, in Corbicula
      fluminea (Mollusca) (in vivo) and CHO-K1 cells (in vitro) using comet assay.
AB  - The comet assay was utilized to investigate the quality of water from seven
      locations along the Cambe Stream, in vivo (Corbicula fluminea hemolymph), in
      vitro (CHO-K1 cells), in situ, and in laboratory studies. The Cambe Stream basin
      (Londrina, PR, Brazil) is almost completely urbanized and receives different
      forms of industrial and domestic runoff. The data indicated the occurrence of DNA
      damage in cells examined in vivo and in vitro, shown by the significant increase
      in frequencies of cells with DNA damage after exposure to water from all seven
      locations used in the study. Our results strongly suggest the presence of
      genotoxic agent(s) in water at all of the sampled locations, demonstrated by
      elevated numbers of cells with DNA damaged in field and laboratory tests. In all
      of the places sampled, domestic sewage influence appeared to be one important
      cause for the introduction of xenobiotics, environmental genotoxins, and
      pollutants into the water. Thus, the comet assay applied in these cell systems
      was able to detect adverse environmental conditions, proving to be a very
      adequate short-term test and should be included in batteries of tests utilized in
      the monitoring of aquatic environments.

PMID- 20037783
TI  - Bioaccumulation of polycyclic aromatic hydrocarbons in gilthead sea bream (Sparus
      aurata L.) exposed to long term feeding trials with different experimental diets.
AB  - Polycyclic aromatic hydrocarbons (16 EPA list) were determined in oils, fish
      feed, and fillets from gilthead sea bream fed through a full production cycle (14
      months) with feed containing different proportions of fish oil replaced by
      vegetable oils, followed by a finishing phase with fish oil. At the beginning of
      the study, fish presented 46.6 microg/kg fresh weight of the sum of PAHs in
      fillet and a benzo[a]pyrene equivalent value of 9.1 microg/kg fresh weight. These
      levels decreased after 330 days of rearing to values around 2 microg/kg. Although
      the concentration increased again during the finishing phase, they remained low.
      These low concentrations of PAHs could be the result of a dilution process
      associated with fish growth and with the detoxification pathways, both favored by
      the low levels of PAHs present in the feeds and the lack of any other potential
      source of contamination during the whole rearing period.

PMID- 20037784
TI  - Nigerian Bonny light crude oil disrupts antioxidant systems in testes and sperm
      of rats.
AB  - Nigerian Bonny light crude oil (BLCO) is commonly used by the local population in
      folklore medicine for the management of various forms of gastrointestinal
      problems and male reproductive capacity. The study investigated the effects of
      BLCO on the antioxidant systems of the testes and epidydimal sperm in rats by
      oral exposure to 0, 200, 400 and 800 mg/kg BLCO for 7 days. In testes and sperm,
      BLCO treatment at all doses significantly (p<0.05) decreased superoxide dismutase
      (SOD), catalase (CAT), and glutathione S-transferase (GST) activities, whereas it
      markedly increased glucose 6-phosphate dehydrogenase (G6PD) and gamma glutamyl
      transferase (GGT) activities as well as increased glutathione (GSH), hydrogen
      peroxide, and malondialdehyde (MDA) levels in all treatment groups. Although
      epididymal sperm number (ESN), daily spermatozoa production (DSP), and sperm
      motility were significantly decreased, total sperm abnormalities were
      significantly increased without affecting sperm viability at all dose levels
      compared with controls. The adverse effect of BLCO on TSN was noted at the 800
      mg/kg dose only. Histopathology results showed treatment-related lesions of the
      testes characterized by severe congestion of interstitial vessels, decreased
      germinal epithelium, and increased number of vacuolization. These results suggest
      that exposure to BLCO, such as its use in ailment management, may promote
      infertility by altering the function of the testes and sperm, particularly by way
      of induction of oxidative stress.

PMID- 20037785
TI  - Metals in feathers of black-crowned night-heron (Nycticorax nycticorax) chicks
      from the New York Harbor Estuary.
AB  - In heavily urbanized landscapes such as the New York Harbor Estuary, the local
      environment is subject to a variety of contamination sources. Environmental
      contaminants such as heavy metals and metalloids pose a risk to wildlife
      inhabiting the harbor. Metal concentrations in feathers indicate exposure and
      provide insight into the potential adverse effects on birds. In 2004 and 2005
      down feathers were collected from 147 black-crowned night heron (Nycticorax
      nycticorax) chicks living on four island colonies in the New York Harbor Estuary,
      USA: Goose Island, Hoffman Island, North Brother Island, and Canarsie Pol. We
      examined geographical and interannual differences in concentrations of the
      metalloid arsenic (As) and the heavy metals cadmium (Cd), chromium (Cr), lead
      (Pb), and mercury (Hg). Significant differences in metal concentrations were a
      function of location, with North Brother Island having the highest As
      concentrations and Goose Island having the highest Cr and Pb concentrations in
      feathers collected in 2004. In 2005, feather samples indicated Hoffman Island had
      the highest Cr concentrations and North Brother Island had the highest Pb and Hg
      concentrations. Concentrations of As, Cd, and Hg decreased significantly from
      2004 to 2005 on North Brother Island, Hg on Hoffman Island decreased from 2004 to
      2005, while Cr on Hoffman Island increased from 2004 to 2005. Cd and Pb
      concentrations were higher and As and Cr concentrations were generally lower than
      concentrations reported in previous studies. Further investigation is necessary
      on the declining population of herons in the New York Harbor Estuary to determine
      specifically if birds are experiencing adverse effects from metal contaminants,
      or if organic contaminants, such as organic Hg or polychlorinated biphenyls
      (PCBs), are playing a role in this population's decline.

PMID- 20037786
TI  - Nasal leech infestation: report of seven leeches and literature review.
AB  - Nasal leech infestation rarely occurs in society today and it is usually reported
      as an anecdote. In this study, we present seven nasal leeches in six patients
      from 1984 to 2008. All patients initially presented with epistaxis. Four patients
      were less than 8 years old and two patients were older than 60 years old. All
      patients had spent time in rural streams 2 weeks to 2 months before the symptoms
      occurred. All of the seven leeches were removed smoothly and one leech migrated
      to the oropharynx during the operation. The length of the leeches ranged from 2
      to 12 cm with an average length of 4.6 cm. Attention should be given to nasal
      leech infestation, especially in children and senior citizens who have visited
      rural streams and have been exposed to freshwater. One of our patients had two
      leeches lodged in his nasal cavities. Therefore, it is also important to re
      examine both nasal cavities after the removal of one leech.

PMID- 20037787
TI  - Intraarterial chemotherapy: a valid option in the treatment of verrucous
      carcinoma?

PMID- 20037788
TI  - Current potential and limitations of molecular diagnostic methods in head and
      neck cancer.
AB  - Traditional diagnostic methods such as clinical assessment, histopathological
      examination and imaging techniques are limited in their capacity to provide
      information on prognosis and treatment choice of head and neck cancer. In recent
      years, molecular techniques have been developed that enabled us to get more
      insight into the molecular biological cellular pathways underlying tumor
      progression and metastasis. Correlation of these molecular changes with clinical
      events has been explored. However, consistently useful markers have not been
      identified yet, although many promising developments are in progress. It may be
      expected that in the near future, molecular markers will be useful for clinical
      purposes. In this paper, an overview will be given of the several molecular
      techniques that may have potential to be introduced in clinical practice in the
      management of head and neck squamous cell carcinoma.

PMID- 20037789
TI  - Progression-free survival in first-line chemotherapy is a prognostic factor in
      second-line chemotherapy in patients with advanced gastric cancer.
AB  - PURPOSE: First-line chemotherapy (Cx-1) in advanced gastric cancer (AGC) provides
      survival benefit. However, it is unclear who should proceed to second-line
      chemotherapy (Cx-2). METHODS: We reviewed patients who received Cx-2 for AGC
      following progressive disease after Cx-1 from 2000 to 2005 at the National Cancer
      Center Hospital, Tokyo. To evaluate the prognostic factors in Cx-2, Cox
      regression multivariate analysis was performed. RESULTS: Of 995 patients who
      received Cx-1 in this study period, 466 met the eligibility criteria. The median
      progression-free survival in Cx-1 (PFS-1) was 133 days. The median survival time
      from the date of starting second-line chemotherapy (MST-2) was 207 days.
      Multivariate analysis revealed that the factors affecting short survival time in
      Cx-2 were poor performance status (> or = 2), low serum albumin level (<3.5
      mg/dL), elevated C-reactive protein level (> or = 1.0 mg/dL), patients with bone,
      liver or peritoneal metastasis, and patients without previous gastrectomy (p <
      0.01). PFS-1 was an independent prognostic factor for survival (PFS-1 <120, MST-2
      133 days, PFS-1 > or = 120, MST-2 258 days, hazard ratio 0.71, 95% confidence
      interval 0.58-0.86, p < 0.01). The Cx-2 regimen (irinotecan vs. taxane) did not
      correlate with survival. CONCLUSION: PFS-1 is one of the prognostic factors of Cx
      2 in patients with AGC.

PMID- 20037792
TI  - Cancer incidence in the vicinity of Finnish nuclear power plants:  an emphasis on
      childhood leukemia.
AB  - The objective of this paper was to study cancer incidence, especially leukemia in
      children (<15 years), in the vicinity of Finnish nuclear power plants (NPPs). We
      used three different approaches: ecological analysis at municipality level,
      residential cohorts defined from census data, and case-control analysis with
      individual residential histories. The standardized incidence ratio of childhood
      leukemia for the seven municipalities in the vicinity of NPPs was 1.0 (95% CI
      0.6, 1.6) compared to the rest of Finland. The two cohorts defined by censuses of
      1980 and 1990 gave rate ratios of 1.0 (95% CI 0.3, 2.6) and 0.9 (95% CI 0.2,
      2.7), respectively, for childhood leukemia in the population residing within 15
      km from the NPPs compared to the 15-50 km zone. The case-control analysis with 16
      cases of childhood leukemia and 64 matched population-based controls gave an odds
      ratio for average distance between residence and NPP in the closest 5-9.9 km zone
      of 0.7 (95% CI 0.1, 10.4) compared to > or =30 km zone. Our results do not
      indicate an increase in childhood leukemia and other cancers in the vicinity of
      Finnish NPPs though the small sample size limits the strength of conclusions. The
      conclusion was the same for adults.

PMID- 20037791
TI  - Genes involved with folate uptake and distribution and their  association with
      colorectal cancer risk.
AB  - Folate status is an important predictor of colorectal cancer risk. Common genetic
      variants in genes involved in regulating cellular folate levels might also
      predict risk, but there are limited data on this issue. We conducted a family
      based case-control association study of variants in four genes involved in folate
      uptake and distribution: FOLR1, FPGS, GGH and SLC19A1, using 1,750 population
      based and 245 clinic-based cases of pathologically confirmed colorectal cancer
      and their unaffected relatives participating in the Colon Cancer Family
      Registries. Standardized questionnaires, administered to all participants,
      collected information on risk factors and diet. Standard molecular techniques
      were used to determine microsatellite instability (MSI) status on cases. tagSNPs
      (n = 29) were selected based on coverage as assessed by pairwise r2. We found no
      evidence that tagSNPs in these genes were associated with risk of colorectal
      cancer. For the SLC19A1-rs1051266 (G80A, Arg27His) missense polymorphism, the A/A
      genotype was not associated with risk of colorectal cancer using population-based
      (OR = 1.00; 95% CI = 0.81-1.23) or clinic-based (OR = 0.75; 95% CI = 0.44-1.29)
      families compared to the G/A and G/G genotypes. We found no evidence that the
      association between any tagSNP and CRC risk was modified by multivitamin use,
      folic acid use and dietary folate intake and total folate intake. The odds ratios
      were similar, irrespective of MSI status, tumor subsite and family history of
      colorectal cancer. In conclusion, we found no significant evidence that genetic
      variants in FOLR1, GGH, FPGS and SLC19A1 are associated with the risk of
      colorectal cancer.

PMID- 20037793
TI  - Pituitary function in subjects with mild traumatic brain injury: a review of
      literature and proposal of a screening strategy.
AB  - Traumatic brain injury (TBI) is an important public health problem all over the
      world. The level of consciousness of the patients and the severity of the brain
      injury is commonly evaluated by the Glascow Coma Scale as mild, moderate and
      severe TBI. When we consider the high frequency of mild TBI (MTBI) among the all
      TBI patients the burden of the pituitary dysfunction problem in this group could
      not be ignored. However, one of the most important and still unresolved questions
      is which patients with MTBI should be screened for hypopituitarism? Another type
      of head trauma which could be considered as the subgroup of MTBI is sports
      related chronic repetitive head trauma. Therefore, in this review we will discuss
      the frequency, characteristics and current management of pituitary dysfunction in
      patients with MTBI including the subjects exposed to sports related chronic mild
      head trauma.

PMID- 20037794
TI  - Possible biosynthetic pathways for all cis-3,6,9,12,15,19,22, 25,28
      hentriacontanonaene in bacteria.
AB  - A very long chain polyunsaturated hydrocarbon, hentriacontanonaene (C31:9), was
      detected in an eicosapentaenoic acid (EPA)-producing marine bacterium, which was
      isolated from the mid-latitude seashore of Hokkaido, Japan, and was tentatively
      identified as mesophilic Shewanella sp. strain osh08 from 16S rRNA gene
      sequencing. The geometry and position of the double bonds in this compound were
      determined physicochemically to be all cis at positions 3, 6, 9, 12, 15, 19, 22,
      25, and 28. Although C31:9 was detected in all of the seven EPA- or/and
      docosahexaenoic acid-producing bacteria tested, an EPA-deficient mutant (strain
      IK-1Delta8) of one of these bacteria had no C31:9. Strain IK-1Delta8 had defects
      in the pfaD gene, one of the five pfa genes responsible for the biosynthesis of
      EPA. Although Escherichia coli DH5alpha does not produce EPA or DHA inherently,
      cells transformed with the pfa genes responsible for the biosynthesis of EPA and
      DHA produced EPA and DHA, respectively, but not C31:9. These results suggest that
      the Pfa protein complex is involved in the biosynthesis of C31:9 and that pfa
      genes must not be the only genes responsible for the formation of C31:9. In this
      report, we determined for the first time the molecular structure of the C31:9 and
      discuss the possible biosynthetic pathways of this compound.

PMID- 20037795
TI  - Rumen bacterial diversity dynamics associated with changing from bermudagrass hay
      to grazed winter wheat diets.
AB  - Rumen bacterial communities in forage-fed and grazing cattle continually adapt to
      a wide range of changing dietary composition, nutrient density, and environmental
      conditions. We hypothesized that very distinct community assemblages would
      develop between the fiber and liquid fractions of rumen contents in animals
      transitioned from bermudagrass hay diet to a grazed wheat diet. To address this
      hypothesis, we designed an experiment utilizing a 16S-based bTEFAP pyrosequencing
      technique to characterize and elucidate changes in bacterial diversity among the
      fiber and liquid rumen fractions and whole rumen contents of 14 (Angus x
      Hereford) ruminally cannulated steers sequentially fed bermudagrass hay (Cynodon
      dactylon; 34 days) and grazing wheat forage (28 days). Bermudagrass hay was a
      conserved C4 perennial grass lower in protein and higher in fiber (11% and 67%,
      respectively) content than grazed winter wheat (Triticum aestivum), a C3 annual
      grass with higher protein (20%) and a large (66%) soluble fraction.Significant
      differences in the OTU estimates (Chao1, Ace,and Rarefaction) were detected
      between fractions of both diets, with bermudagrass hay supporting greater
      diversity than wheat forage. Sequences were compared with a 16S database using
      BLASTn and assigned sequences to respective genera and genera-like units based on
      the similarity value to known sequences in the database. Predominant genera were
      Prevotella (up to 33%) and Rikenella-like (upto 28%) genera on the bermudagrass
      diet and Prevotella (upto 56%) genus on the wheat diet irrespective of the
      fractions. Principle component analyses accounted for over 95% of variation in
      16S estimated bacterial community composition in all three fractions and clearly
      differentiated communities associated with each diet. Overall, bermudagrass hay
      diets clustered more clearly than wheat diets.These data are the first to explore
      bacterial diversity dynamics in a common population of animals in response to
      contrasting grass forage diets.

PMID- 20037796
TI  - Neuritis ossificans of the common peroneal nerve.

PMID- 20037799
TI  - Biosynthesis of acteoside in cultured cells of Olea europaea.
AB  - Five phenylethanoid glycosides (acteoside, isoacteoside, beta-oxoacteoside, beta
      hydroxyacteoside, and salidroside) were isolated from a cell suspension culture
      of Olea europaea. We examined the biosynthesis of acteoside in olive cell
      cultures by using feeding experiments with stable isotope labeled precursors. The
      hydroxytyrosol moiety of acteoside is biosynthesized from tyrosine through
      dopamine, whereas the caffeoyl moiety of acteoside is biosynthesized from
      phenylalanine via a cinnamate pathway. Dopamine is incorporated into acteoside
      through oxidation to the corresponding aldehyde, reduction to the alcohol, and
      then beta-glycosylation.

PMID- 20037800
TI  - Free radical scavengers from the aerial parts of Euphorbia petiolata.
AB  - Reversed-phase preparative high-performance liquid chromatography (HPLC) of the
      methanol extract of the aerial parts of Euphorbia petiolata Banks & Soland, an
      endemic Iranian medicinal plant, yielded ten free radical scavengers including
      eight flavonoid glycosides myricetin 3-O-glucoside (1), kaempferol 3-O-(2-O
      galloyl)-glucoside (2), myricetin 3-O-rhamnoside (3), quercetin 3-O-glucoside
      (4), kaempferol 3-O-glucoside (5), quercetin 3-O-rhamnoside (6), kaempferol 3-O
      rhamnoside (7), and quercetin 3-O-rutinoside (10), a coumarin esculetin (8) and a
      phenylpropanoid 2-hydroxydihydrocinnamic acid (9). The structures of these
      compounds were elucidated conclusively by spectroscopic means and also by direct
      comparison of their spectroscopic data with respective published data. The free
      radical scavenging properties of these compounds were assessed by the 2,2
      diphenyl-1-picrylhydrazyl assay.

PMID- 20037801
TI  - Phytochemical analysis of an antiviral fraction of Radix astragali using HPLC-DAD
      ESI-MS/MS.
AB  - Radix astragali (Huangqi in Chinese) is a well-known traditional Chinese
      medicinal herb that has been used clinically in China for centuries to cure
      various diseases. To profile the antiviral constituents of this herb, a high
      performance liquid chromatography-diode array detector-electrospray ionization
      tandem mass spectrometry (HPLC-DAD-ESI-MS/MS) analytical method was developed to
      separate and determinate the active part of the extract of Radix astragali, which
      showed potent inhibition of several viruses. By comparing their retention time
      and MS data with those obtained from the authentic compounds and the published
      data, a total of 18 compounds, comprising 11 flavonoids and 7 saponins, were
      identified. This study provides an approach to rapidly characterize bioactive
      constituents in traditional Chinese medicines (TCMs).

PMID- 20037802
TI  - Composition of endophytic fungi living in Cinchona ledgeriana (Rubiaceae).
AB  - A total of 21 endophytic filamentous fungi were isolated from the young stems of
      Cinchona ledgeriana (Rubiaceae) cultivated in West Java, Indonesia. They were
      classified into six genera, namely nine Phomopsis spp., six Diaporthe spp., two
      Schizophyllum spp., two Penicillium spp., one Fomitopsis sp., and one Arthrinium
      sp. by using nucleotide sequence analysis of the internal transcribed spacers
      (ITS1 and ITS2) including 5.8S ribosomal DNA region and phylogenetic analysis.

PMID- 20037803
TI  - A new phenolic compound, 4-dehydrochebulic acid-1,6-dimethyl ester from Sapium
      insigne leaves.
AB  - A new phenolic compound, 4-dehydrochebulic acid-1,6-dimethyl ester (2) was
      isolated from the leaves of Sapium insigne (Royle) Benth. ex Hook. fil.
      (Euphorbiaceae) along with three known compounds gallic acid (1), brevifolin
      carboxylic acid (3) and fraxin (4). Structures of those compounds were elucidated
      on the basis of spectroscopic data.

PMID- 20037806
TI  - Bioluminescent assay of microbial ATP in postmortem tissues for the estimation of
      postmortem interval.
AB  - To study the relationship between changes of microbial ATP in four kinds of
      murine tissues and the postmortem interval (PMI), healthy SD rats were sacrificed
      and their muscles, livers, spleens and kidneys were sampled at different
      postmortem intervals. The concentration of microbial ATP was detected using
      bioluminescent assay and the data was statistically analyzed. The concentration
      of microbial ATP in muscle increased with PMI time. The peak appeared at the 7th
      day after death, and at the 10th day, microbial ATP in muscle tissue increased
      again. In internal organs, the peaks of microbial ATP were observed at the 8th
      day after death and the level decreased during 8-10 d. The differences in
      microbial ATP concentration in liver, spleen and kidney were not statistically
      significant. During day 0 to day 9 after death, the correlation was best between
      PMI and microbial ATP in muscle. With PMI as the independent variable, the cubic
      polynomial regression equation was Y=0.02X(3)-0.166X(2)-0.666X+13.412 (R
      (2)=0.989, P<0.01). In internal organs, the best correlation was found between
      PMI and microbial ATP during day 0 to day 10. With PMI as the independent
      variable, the cubic polynomial regression equation was Y=0.016X(3)-0.127X(2)
      0.809X+13.324 (R (2)=0.986, P<0.01). There existed high correlations between PMI
      and microbial ATP concentration in rat tissues. Since only a small amount of
      tissue was needed for the detection and the sample was not affected by self
      decomposition, the method may extend the time range of PMI estimation.

PMID- 20037807
TI  - Effect of renin angiotensin system blockade on the islet microvessel density of
      diabetic rats and its relationship with islet function.
AB  - To investigate the effects of rennin angiotensin system blockade on the
      microvessel density in islets of diabetic rats and its relationship with islet
      function, diabetes model was created by feeding of high-caloric laboratory chow
      plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg).
      After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10),
      the islet function of the animals was evaluated by intravenous insulin release
      test (IVIRT). The pancreases were immunohistochemically stained to analyze the
      content of insulin and vascular endothelial growth factor (VEGF) in the islets.
      The microvessel density (MVD) of islets was detected by counting CD34 positive
      cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets
      was detected by RT-PCR. Compared with normal control group (NC, n=10), the area
      under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM,
      n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell
      was decreased significantly; the relative content of VEGF was increased obviously
      [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the
      relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01).
      Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6%
      and 34.9% respectively; IRC was also increased significantly; the relative
      content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased
      by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was
      decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no
      significant differences in the said indexes between group AE and AR. It is
      concluded that the blockade of RAS may ameliorate islets function of diabetic
      rats by increasing the MVD in islets.

PMID- 20037808
TI  - Liver-specific reduction of Mfn2 protein by RNAi results in impaired
      glycometabolism and lipid homeostasis in BALB/c mice.
AB  - Mitofusin-2 (Mfn2) gene expression is positively correlated with insulin
      sensitivity in patients with type 2 diabetes. However, it is unclear if Mfn2 is
      involved in carbohydrate metabolism and lipid homeostasis. In order to
      investigate the specific functions of Mfn2 in glycometabolism and lipid
      homeostasis in BALB/c mice, a RNA interference technique-mediated hydrodynamic
      injection was developed, in which short hairpin RNAs (shRNAs) were used to
      inhibit the Mfn2 expression in vivo. Seventy-two mice were randomly divided into
      two groups: the Mfn2 reduction group (Mfn2/shRNA) and the negative control group
      (NC). Intraperitoneal glucose tolerance tests and intraperitoneal insulin
      tolerance tests were used to evaluate glycometabolism and insulin sensitivity. D
      (3-3H) glucose or 3H2O was injected into the tail vein or intraperitoneally to
      facilitate the calculation of the rate of hepatic glucose production and fatty
      acid synthesis in vivo. The results showed that, in Mfn2/shRNA mice, the liver
      Mfn2 protein was significantly decreased, and fasting blood glucose
      concentrations were increased by approximately 48%, when compared with the NC
      mice. In parallel with the changes in fasting glucose levels, hepatic glucose
      production was significantly elevated in Mfn2/shRNA mice. When insulin was
      administrated, these mice exhibited impaired insulin tolerance. It was also found
      that the reduction of Mfn2 markedly decreased the rate of fatty acid synthesis in
      the liver, and the Mfn2/shRNA mice exhibited hypertriglyceridema. Taken together,
      our results indicate that Mfn2 plays an important role in maintaining glucose and
      lipid homeostasis, and in the development of insulin resistance in vivo.

PMID- 20037809
TI  - Expressions of tissue factor and tissue factor pathway inhibitor in patients with
      acute graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation.
AB  - This study examined the expressions of human serum tissue factor (TF) and tissue
      factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease
      (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and
      their clinical significance. The serum TF and TFPI levels were detected by ELISA
      in 28 allo-HSCT recipients before and after the transplantation and the changes
      of TF and TFPI levels were dynamically monitored at different phases of the
      disease. No significant differences in the serum TF and TFPI levels were found in
      allo-HSCT recipients in the absence of aGVHD or with grade I aGVHD before and
      after the transplantation. The levels of serum TF and TFPI were substantially
      increased in the patients with gradeII aGVHD at the peak of aGVHD (P<0.05) and
      they were even higher in the patients with grade III-IV aGVHD (P<0.01). When the
      conditions became stable after treatment with immunosuppressive agents, the serum
      TFPI level was decreased to the baseline level (P>0.05) and the TF level was
      lowered but still higher than the baseline level (P<0.05). It was concluded that
      the levels of serum TF and TFPI were increased significantly in the patients with
      grade II-IV aGVHD after allo-HSCT and decreased markedly after the treatment.
      Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is
      important to predict the occurrence, outcome and prognosis of aGVHD.

PMID- 20037810
TI  - Central opioid peptide-containing neurons mediates therapeutic effect of short
      pulse gastric electrical stimulation on dyspepsia-like symptoms in dogs.
AB  - This study investigated whether the curative effect of short-pulse gastric
      electrical stimulation (GES) on the vasopressin-induced dyspeptic symptoms was
      mediated by central opioid peptide-producing neurons. Five female beagle dogs
      implanted with 1 pair of electrodes in gastric serosa were used in a two
      experiment study. In experiment one, the brain was scanned by positron emission
      tomography in 3 dogs with and without short-pulse GES, and the radioactivity in
      nuclei of solitary tract (NST) and hypothalamus was detected. Experiment two was
      composed of 4 sessions. In session one, the dogs were injected with vasopressin
      in the absence of short-pulse GES. With session two, the short-pulse GES was
      simultaneously given via the electrodes with the injection of vasopressin. In
      sessions three and four, naloxone and naloxone methiodide was administered
      respectively in the presence of short-pulse GES. Motion sickness-like symptoms
      were scored and compared among the different sessions. The results showed that
      the short-pulse GES significantly increased the radioactivity in NST and
      hypothalamic nuclei (P<0.05, vs control). The short-pulse GES could ameliorate
      the vasopressin-induced motion sickness-like symptoms in dogs. Naloxone, but not
      naloxone methiodide could attenuate the curative effects of short-pulse GES. It
      is concluded that NST and hypothalamic nuclei may participate in the mediation of
      the curative effects of short-pulse GES on dyspepsia-like symptoms. Central
      opioid peptide-containing neurons presumably mediate the therapeutic effect on
      dyspeptic symptoms of short-pulse GES.

PMID- 20037811
TI  - Suppressive effects of genomic imprinted gene PEG10 on hydrogen peroxide-induced
      apoptosis in L02 cells.
AB  - The effects of PEG10 on hydrogen peroxide (H2O2)-induced apoptosis in human
      normal liver cell line L02 were investigated. The PEG10 gene was transfected into
      L02 cells by lipofectamine, the positive clone was screened by G418 and defined
      as L02/PEG10, while the cell transfected with empty expression vector (pEGFP-N1)
      was defined as L02/vector. L02/vector and parental L02 cells served as control.
      RT-PCR and Western blotting were employed to detect the expression of target
      genes. H2O2 (50-400 mmol/L) was administered to induce the apoptosis of L02
      cells. Cells viability was measured by MTT and the morphological changes of
      apoptotic cells were determined by fluorescence microscopy using hoechst33342
      nuclei staining. DNA fragmentation was observed by agarose gel electrophoresis.
      PEG10 mRNA and protein levels in L02/PEG10 cells were significantly increased as
      compared with those in the control cells. After treatment with 400 mmol/L H2O2
      for 24 h, the cellular growth inhibition rate of L02/PEG10 cells was
      significantly lower (58.2%) than that of L02 (92.5%) and L02/vector (88%).
      Distinct morphological changes characteristic of cell apoptosis such as
      karyopyknosis and conglomeration were not observed in L02/PEG10. Ladder-like DNA
      fragmentation in a dose-dependent manner was observed in both L02 and L02/vector
      cell lines, but not in L02/PEG10. PEG10 over-expression significantly inhibited
      cytotoxicity induced by H2O2 on human normal liver cell line L02 by antagonizing
      H2O2-induced apoptosis.

PMID- 20037812
TI  - Albumin modulates the production of matrix metalloproteinases-2 and -9 in
      podocytes.
AB  - To investigate the effects of albumin on the production of matrix
      metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in
      podocytes. Podocytes were treated with bovine serum albumin (BSA) at the
      concentration of 0.1, 0.5, 1, 2 g/L, respectively. Conditioned media were
      harvested 12, 24, 48 and 72 h after the treatment. The expression of MMP-2 and
      MMP-9 was assayed by gelatin zymography, RT-PCR and Western blotting analysis.
      Our results showed that in comparison with the control group, BSA increased the
      expression of MMP-2 and MMP-9 mRNA and protein in a dose- and time-dependent
      manner (P<0.05). Meanwhile, the enzymatic activities of MMP-2 and MMP-9 in the
      culture supernatants of podocytes were also increased (P<0.05). It is concluded
      that albumin up-regulated the expression of MMP-2 and MMP-9 at gene and protein
      levels in a time- and dose-dependent manner.

PMID- 20037813
TI  - Protective effect of sulodexide on podocyte injury in adriamycin nephropathy
      rats.
AB  - This study examined the effect of sulodexide on podocyte injury in rats with
      adriamycin nephropathy (AN). A total of 36 healthy male SD rats were randomly
      assigned to three groups: control group, AN group and sulodexide treatment group.
      Rat models of AN were established by a single tail intravenous injection of
      adriamycin (6.5 mg/kg) in both AN group and sulodexide treatment group.
      Sulodexide (10 mg/kg) was administered the rats in the treatment group once daily
      by garage from the first day of model establishment until the 14th day or the
      28th day. Samples of 24-h urine and renal cortex tissues were harvested at day
      14, 28 after the model establishment. Excretion of 24-h urinary protein was
      measured by Coomassie brilliant blue method. The pathological changes in renal
      tissues were observed by light microscopy and electron microscopy respectively.
      Heparanase mRNA was detected by RT-PCR. Expressions of desmin, CD2AP and
      heparanase were determined by immunohistological staining. The results showed
      that the expressions of heparanase mRNA and protein were increased in the
      glomeruli of AN rats at day 14 and 28 after the model establishment, which was
      accompanied by the increased expression of desmin and CD2AP. The mRNA and protein
      expression of heparanase was decreased in the sulodexide-treated rats as compared
      with AN rats at day 14 and 28. And, the protein expression of desmin and CD2AP
      was reduced as with heparanase in the sulodexide- treated rats. Proteinuria and
      podocyte foot process effacement were alleviated in the AN rats after sulodexide
      treatment. There was a positive correlation between the expression of heparanase
      and the expression of desmin and CD2AP (as well as 24-h urinary protein
      excretion). It was concluded that increased heparanase is involved in podocyte
      injury. Sulodexide can maintain and restore podocyte morphology by inhibiting the
      expression of heparanase in AN.

PMID- 20037814
TI  - A Rho-kinase inhibitor, fasudil, attenuates progressive glomerulosclerosis
      induced by daunorubicin in rats.
AB  - Accumulating evidence suggests that the small G protein Rho and its downstream
      effector Rho kinase may play important roles in kidney biology. The present study
      examined the effects of a Rho-kinase inhibitor, fasudil, on daunorubicin-induced
      progressive glomerulosclerosis and explored the underlying mechanism by which
      fasudil ameliorates glomerulosclerosis. Thirty-six male SD rats were randomly
      allocated into sham-operation group (sham group, n=12), unilateral nephrectomy
      (UNX)+daunorubicin (DRB) group (model group, n=12), UNX+DRB+Fasudil group
      (treatment group, n=12). Two to four weeks after the establishment of the animal
      model, 6 rats in each group were taken randomly for the detection of 24-h urine
      protein excretion. Kidney sections were examined by HE and PAS staining,
      immunohistochemistry and transmission electric microscopy (TEM). The expression
      of Rho-kinase mRNA and P27 mRNA in kidney were detected by RT-PCR. It was found
      that the 24-h urine protein excretion in model group was increased significantly
      as compared with sham group (P<0.01). But this increase was significantly
      suppressed by fasudil (P<0.05). At 4 week, the foot process effacement in
      podocytes, mesangial proliferation and ECM accumulation were observed in model
      group, presenting as focal segmental glomerulosclerosis. But in the treatment
      group, the fasudil alleviated glomerular injury, with proliferating cell nuclear
      antigen (PCNA)-positive cell infiltration ameliorated and the expression of P27
      increased. The expression of Rho-kinase mRNA was significantly enhanced in model
      group and was suppressed in treatment group. Moreover, fasudil up-regulated the
      mRNA expression of P27. Our study demonstrated that the glomerulosclerosis was
      substantially ameliorated by inhibiting the expression of Rho-kinase. It is
      suggested that Rho-kinase pathway is involved in the renal injury and the
      inhibition of Rho-kinase may constitute a therapeutic strategy for the treatment
      of renal injury.

PMID- 20037815
TI  - Depression in patients with Parkinson's disease and the associated features.
AB  - The study was aimed to examine the prevalence of depression in patients with
      Parkinson's disease (PD) and identify its features. A total of 131 out-patients,
      diagnosed as having idiopathic PD in accordance with the United Kingdom
      Parkinson's Disease Society Brain Bank criteria, were interviewed with
      questionnaire and evaluated by Mini-Mental State Examination (MMSE), Unified
      Parkinson's Disease Rating Scale (UPDRS), Hohen &Yahr staging (H&Y staging) and
      Hamilton Rating Scale for Depression (HRSD). Patients were divided into three
      groups in terms of HRSD score: depression group, sub-threshold depression group
      and non-depression group. The clinical variables and symptom profiles were
      obtained and compared among the three groups. The results showed that 27 patients
      (20.6%) fell into the depression group, 71 (54.2%) into the sub-threshold
      depression group, and 33 (25.2%) into the non-depression group. There were no
      differences in age, gender or tremor score among the groups (P>0.05). Significant
      differences were found in duration of PD, UPDRS score, rigidity score and H&Y
      stage between the sub-threshold depression group (or the depression group) and
      the non-depression group (P<0.05). Moreover, the clinical variables in the
      subthreshold depression group had the trend of increasing with the severity of PD
      and their values were similar to those in the depression group. Anhedonia,
      feeling of incapability, sleep disturbance, gastrointestinal symptoms and
      depressive moods were most common in the depression group. And these symptoms
      also were more common in the other two groups. It is concluded that depression
      and sub-threshold depression are common in PD and share similar clinical
      features. Furthermore, subthreshold depression might be the prodrome of
      depression and may develop into depression as the condition progresses.

PMID- 20037816
TI  - Interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma.
AB  - The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in
      gallbladder carcinoma were investigated. By using the immunoprecipitation method,
      the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma
      cell line (Mz-ChA-1) were studied. It was found that there were Rb and E2F1
      proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1
      proteins in the precipitate with anti-Rb. It was concluded that there are
      specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma,
      indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway.
      There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1
      proteins.

PMID- 20037817
TI  - The effects of high-intensity pulsed electromagnetic field on proliferation and
      differentiation of neural stem cells of neonatal rats in vitro.
AB  - The effects of high-intensity pulsed electromagnetic stimulation (HIPEMS) on
      proliferation and differentiation of neonatal rat neural stem cells in vitro were
      investigated. Neural stem cells derived from neonatal rats were exposed to 0.1
      Hz, 0.5-10 Tesla (T) [8 groups of B-I, respectively], 5 stimuli of HIPEMF. The
      sham exposure controls were correspondingly established. Inverted phase contrast
      microscope was used to observe the cultured cells, MTT assay to detect the
      viability of the cells as expressed by absorbance (A) value, and flow cytometry
      to measure differentiation of neural stem cells. The results showed that A values
      of neural stem cells in both 3.0 T and 4.0 T groups were significantly higher
      than the other groups 24 to 168 h post HPEMS, indicating a strong promotion of
      the growth of neural stem cells (P<0.05). The A values of neural stem cells in
      the 6.0 T, 8.0 T, and 10.0 T groups were lower than the sham exposure control
      group, indicating a restraint of the growth of neural stem cells. The rate of
      neuron-specific enolase-positive neurons revealed by flow cytometry in HPEMS
      groups was the same as that in control group (P>0.05). It was suggested that 0.1
      Hz, 5 pulses stimulation of HPEMS within certain scale of intensity (0.5-10.0 T),
      significantly promoted the growth of neural stem cells with the rational
      intensity being 4.0 T.

PMID- 20037818
TI  - Expression of Beclin1 in osteosarcoma and the effects of down-regulation of
      autophagy on the chemotherapeutic sensitivity.
AB  - To explore the expression of Beclin1 in osteosarcoma and investigate the effects
      of down-regulation of autophagy on the chemotherapeutic sensitivity to cisplatin
      (DDP), the expression of Beclin1 in 28 specimens of osteosarcoma (group A) and 19
      specimens of normal bone tissues (group B) were immunohistochemically detected.
      The expression of Beclin1 mRNA in MG63 cells treated with different
      concentrations of DDP was examined with RT-PCR. After down-regulation of
      autophagy in MG63 cells by an autophagy inhibitor, 3-methyladenine (3-MA), the
      cell proliferation inhibition rate of MG63 cells treated with DDP was evaluated
      by using the MTT assay. The positive rates of Beclin1 were 67.85% in group A and
      94.73% in group B. Its expression was lower in osteosarcoma than in normal bone
      tissues, with a significant difference found between them (P<0.05). RT-PCR showed
      that the expression of Beclin1 mRNA in the cells treated with high-dose DDP were
      higher than that in the non-treated cells, and no significant difference in the
      expression of Beclin1 mRNA was found between the cells treated with low-dose DDP
      and the non-treated cells. There was a positive correlation between the level of
      Beclin1 mRNA expression and the concentration of DDP. MTT assay showed that the
      proliferation inhibition rates of the cell treated with 3-MA and DDP combined
      were substantially increased when compared with those treated with DDP alone
      (P<0.01). This study demonstrated that autophagy may be implicated in the
      carcinogenesis of osteosarcoma, and DDP may induce autophagy in the MG63 cells.
      It also suggests that the down-regulated autophagy could increase
      chemotherapeutic sensitivity of DDP to osteosarcoma.

PMID- 20037819
TI  - Skeletal muscle-derived stem cells exhibit cardiocyte competences.
AB  - Adult stem cells from skeletal muscle cells were induced to differentiate into
      cardiocytes to see if stem cells from another different but histologically
      comparable tissues can differentiate to the target cells. Skeletal muscles
      derived stem cells (MDSCs) were isolated from adult skeleton muscle tissues by
      differential adhesion, and immunocytochemically identified by using Sca-1. In
      order to induce the proliferation but not differentiation of MDSCs, the cells
      were cultured in Dulbecco's modified Eagle's medium/F12 (DMEM/F12) supplemented
      with 1:50 B27, 20 ng/mL basic fibroblast growth factor (bFGF), 20 ng/mL epidermal
      growth factor (EGF) in a suspension for 6 days. Then these stem cells were
      treated with 5 mumol/L 5-azacytidine for 24 h in an adherence culture. The
      characteristics of induced cells were examined by immunocytochemistry,
      quantitative real time RT-PCR and morphological observation of cell phenotype.
      Our results showed that the appearance of some cells gradually changed from
      spindle-shape into polygonal or short-column-shape. Some of these post-treated
      cells could contract spontaneously and rhythmically. The expression of GATA-4 and
      cTnT was increased 1 and 2 week(s) after the treatment. And about 16.6% of post
      treated cells were cTnT-positive. Therefore, we are led to conclude that skeletal
      muscle-derived stem cells could differentiate into cardiocyte-like cells, which
      exhibited some characteristics of cardiocytes.

PMID- 20037820
TI  - The single needle method for urethrovesical anastomosis with strengthened
      posterior fixation during laparoscopic radical prostatectomy.
AB  - The single needle method for urethrovesical anastomosis with strengthened
      posterior fixation during laparoscopic radical prostatectomy was explored. The
      method was initiated by performing a fixing suture with a knot at 4 o'clock of
      the posterior lip of bladder neck, and another suture at nearby position was
      performed to leave the knot outside. From 5 o'clock to 8 o'clock, sutures were
      performed every one o'clock to secure posterior approximation, then every two
      o'clock a suture. To avoid a loose anastomosis, lock sutures were performed every
      3 sutures. The needle was always driven full-thickness outside-in in the bladder
      neck and inside-out on the urethra. After completing the full circumference, the
      needle was drawn near the 4 o'clock and tied at the tail end. Any leakage could
      be closed with additional interrupted sutures. The clinical data of 89 patients
      who underwent this method were retrospectively compared with those of 23 patients
      who underwent the single knot method. The results showed that the anastomosis,
      operative and catheterization time was 17.6+/-4.7 min, 134.0+/-10.7 min and
      6.5+1.6 days respectively. There were 3 temporal urinary leakages identified in
      89 cases requiring prolonged catheterization. No urinary leak and anastomotic
      stricture was confirmed, and 95.2% patients had total urinary control. It was
      concluded that this method was simple and safe for urethrovesical anastomosis.

PMID- 20037821
TI  - Attractin gene deficiency contributes to testis vacuolization and sperm
      dysfunction in male mice.
AB  - The effect of loss-of-function of Attractin (Atrn) on the male mouse reproduction
      system was examined in the study. The weights and pathological changes of testes
      and epididymes were compared between Atrn mutant (Atrn(mg-3J)) mice and wild-type
      mice (C3HeB/FeJ) at different months of age. The number and motility of sperms
      were measured in the mutant and control mice. Furthermore, the testicular lactate
      dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these animals were
      detected. The fertility potential of the sperms was observed in vivo and in
      vitro. The results showed that the testes of 3-month-old Atrn (mg-3J) mice
      experienced no significantly different pathological changes from the control mice
      at the same month of age but the SDH activity was substantially reduced. In the 5
      month-old mutant mice, as compared with the control mice, mild vacuolation was
      found in the testes, the density and motility of sperms were decreased in the
      epididymes, the sperm fertility was impaired and the testicular enzyme activity
      was reduced. It is concluded that the age-related Atrn gene progressively loses
      its function and can cause testis vacuolation and impaired sperm function, which
      may be responsible for the impairment of male reproductive ability.

PMID- 20037822
TI  - Implication of expression of osteopontin and its receptor integrin alphanubeta3
      in the placenta in the development of preeclampsia.
AB  - To investigate the expression of osteopontin (OPN) and its receptor integrin
      alphanubeta3 in the placental tissue from pregnant women complicated with
      preeclampsia, the expression of OPN and alphanubeta3 in the placenta of the
      pregnant women with preeclampsia and healthy pregnant women was detected by
      immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN
      and alphanubeta3 protein were expressed in the placenta from normal pregnant
      woman and those with preeclampsia. OPN was located in the placental
      syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and
      integrin alphanubeta3 was mainly expressed on the surface of trophoblast cells.
      Expression of OPN and integrin alphanubeta3 in the placental tissue from
      preeclampsia subjects was significantly lower than that from the control group
      (P<0.05). Compared with the control group, expression of OPN in the placental
      tissue from preeclampsia group was significantly lower (P<0.05) but there was no
      significant difference in the expression of alphanu and beta3 between the
      preeclampsia group and the controls. It is concluded that OPN and its receptor
      integrin alphanubeta3 may be involved in the pathogenesis of preeclampsia.

PMID- 20037823
TI  - Effects of ursolic acid on the proliferation and apoptosis of human ovarian
      cancer cells.
AB  - This study examined the effects of ursolic acid (UA) on the proliferation and
      apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were
      cultured in the RPMI 1640 media and treated with different concentrations of UA
      (0, 10, 20, 40 micromol/L). The proliferation rate of the CAOV3 cells was
      determined by MTT assay. The apoptosis rate was measured by flow cytometry. ERK
      activity was detected by immunoprecipitation and the expressions of p-ERK1/2, MKP
      1, Bax and Bcl-2 by Western blotting. The results showed that the proliferation
      rate was significantly decreased in the cells treated with UA as compared with
      that in the non-treated cells (P<0.05). The intracellular ERK activity and p
      ERK1/2 expression were also reduced in the UA-treated cells, while the MKP-1
      expression was elevated. Moreover, the apoptosis was found in the CAOV3 cells
      exposed to UA; the Bax expression was increased and the Bcl-2 expression
      decreased. The apoptosis rate in the UA-treated cells was much higher than that
      in the non-treated cells (P<0.05). It is concluded that UA can inhibit the
      proliferation of CAOV3 cells by suppressing the ERK activity and the expression
      of p-ERK1/2. And it can also induce the apoptosis of the CAOV3 cells by up
      regulating the Bax expression and down-regulating the Bcl-2 expression.

PMID- 20037824
TI  - A comparative study on the enhancement efficacy of specific and non-specific iron
      chelators for protoporphyrin IX production and photosensitization in HaCat cells.
AB  - The iron chelators can be utilized in target cells to improve 5-aminolaevulinic
      acid (ALA)-based photodynamic therapy (PDT). The purpose of this study is to
      compare the effect of two kinds of iron chelators, desferrioxamine (DFO) and
      ethylenediaminetetraacetic acid (EDTA) on the enhancement of ALA-PDT. HaCat cells
      were cultured in medium containing 2.0 mmol/L of ALA and 0.5 mmol/L of DFO or
      EDTA. After 3-h incubation in the dark, the concentration of cellular
      protoporphyrin IX (PpIX) was detected by high performance liquid chromatography
      (HPLC), and the fluorescence of PpIX was observed at 630 nm emission under
      confocal laser scanning microscope. For PDT, HaCat cells were irradiated using
      632.8 nm laser, and the fractions of apoptotic and necrotic cells were flow
      cytometrically assayed. Related differences in morphology and ultrastructure of
      Ha-Cat cells were observed using optical microscope or transmission electron
      microscope. Compared to incubation with ALA alone, the addition of DFO or EDTA
      increased the concentration of cellular PpIX and the fluorescent density of PpIX,
      and also increased cell death ratio after PDT. PDT using ALA plus DFO produced
      the highest cellular PpIX level, greatest cell death ratio and most severe
      structural damage to the cells. It was concluded that both DFO and EDTA could
      enhance ALA-based PpIX production and PDT. Compared to the non-specific iron
      chelator of EDTA, the specific chelator, DFO, showed more potential for the
      enhancement.

PMID- 20037825
TI  - EGCG enhances TRAIL-mediated apoptosis in human melanoma A375 cell line.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      anti-cancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic
      constituent of green tea. In this study, inhibitory effect of combined use of
      EGCG and TRAIL on human melanoma A375 cells was examined and the possible
      mechanism investigated. The cells were divided into 4 groups: control group, EGCG
      group (EGCG: 10, 20 mug/mL), TRAIL group (TRAIL: 25 ng/mL) and EGCG+TRAIL group
      (combined group). The growth inhibition was measured in the A375 cells treated
      with different concentrations of TRAIL ((25, 50, 75, 100, 125, 150 ng/mL) by MTT
      assay. The apoptosis was assessed by flow cytometry. The expressions of DR4 and
      DR5 were detected by flow cytometry and western blotting. The activities of
      caspase-8 and caspase-3 were determined by colorimetric assay. The results showed
      that TRAIL could dose-dependently inhibit the growth of A375 cells and the IC(50)
      of TRAIL was 150 ng/mL. The apoptosis rate was 11.8% in the TRAIL group, 5%-7% in
      the EGCG group and 48.9%-59.1% in the combined group. Significant difference was
      found in the apoptosis rate between the combined group and the EGCG or TRAIL
      group (P<0.05 for each). The expression of DR4 instead of DR5 was significantly
      increased in the EGCG group. The activity of caspase-3 rather than caspase-8 was
      substantially enhanced in the EGCG group. These results suggest that EGCG is
      useful for the TRAIL-based treatment for melanoma.

PMID- 20037826
TI  - Expression of hypoxia-inducible factor-1alpha in liver tumors after transcatheter
      arterial embolization in an animal model.
AB  - To examine the effect of transcatheter arterial embolization (TAE) of liver
      tumors on hypoxia-inducible factor-1alpha (HIF-1alpha) expression in the residual
      viable tumor, a total of 30 New Zealand White rabbits implanted with VX2 liver
      tumor were divided into 2 groups. TAE-treated group animals (n=15) were subjected
      to TAE with 150-250 microm polyvinyl alcohol particles. Control group animals
      (n=15) underwent sham embolization with distilled water. Six hours, 3 days or 7
      days after TAE, the animals were sacrificed, and samples of tumor and adjacent
      normal liver tissue were harvested. Expression of HIF-1alpha protein was examined
      immunohistochemically. Real-time PCR was performed to examine the HIF-1alpha mRNA
      levels. Our results showed that HIF-1alpha protein was expressed in the VX2
      tumors but not in the adjacent normal liver tissue. The HIF-1alpha-positive tumor
      cells were located predominantly at the periphery of necrotic tumor regions. The
      mean levels of HIF-1alpha protein were significantly higher in TAE-treated tumors
      than those in control tumors (P=0.002). Among the three sacrificing time points,
      the difference in increase in HIF-1alpha protein was significant between the two
      groups at the sacrificing time point of 6 h and 3 days after TAE (P=0.020,
      P=0.031, respectively), whereas no significant increase was noted 7 days after
      TAE (P=0.502). In contrast, although HIF-1alpha mRNA was expressed in TAE-treated
      and control VX2 tumors, there existed no significant difference in the HIF-1alpha
      mRNA level between the two groups (P=0.372). It is concluded that TAE of liver
      tumors increases the expression of HIF-1alpha at protein level in the residual
      viable tumor, which could be attributed to hypoxia generated by the procedure.

PMID- 20037827
TI  - Assessment of ascending aortic elasticity in hypertension patients by
      quantitative tissue velocity imaging.
AB  - The elasticity of the ascending aorta in healthy volunteers and hypertension
      patients were examined by using quantitative tissue velocity imaging (QTVI), and
      the age-related change in the ascending aortic elasticity was investigated. The
      anterior and posterior walls of the ascending aorta were imaged with tissue
      Doppler method in all the subjects and QTVI was performed. Stable curves were
      obtained from 173 hypertension patients and 185 healthy adults. The peak early
      diastolic velocity (V(e)), peak late diastolic velocity (V(a)) and peak systolic
      velocity (V(s)) were measured. The relation of age with these measures was
      assessed. The results showed that the elasticity of the ascending aorta was much
      lower in the hypertension patients than in normal controls (P<0.05), and the
      elasticity was decreased with age in both groups (P<0.05). Our results suggested
      that QTVI, a new non-invasive ultrasonic technique, is helpful for the assessment
      of the aortic elasticity in hypertension patients.

PMID- 20037828
TI  - Assessment of regional left ventricular myocardial function in rats after acute
      occlusion of left anterior descending artery by two-dimensional speckle tracking
      imaging.
AB  - This study evaluated the change in regional left ventricular myocardial function
      in rats following acute occlusion of the left anterior descending coronary artery
      (LAD) by using two-dimensional speckle tracking imaging (2D-STI). Sixty Wistar
      rats were randomly divided into two groups, a myocardial infarction (MI) group,
      in which 50 rats were subjected to LAD occlusion for 30-45 min, and a sham
      operated (SHAM) group that contained 10 rats serving as control. Echocardiography
      was performed at baseline and 1, 4 and 8 week(s) after the operation. High
      frequency two-dimensional images of left ventricular short axis at papillary
      muscle level were recorded. Peak systolic radial strain (PRS) and circumferential
      strain (PCS) were measured in the mid-ventricle in short-axis view by using
      EchoPAC workstation. Left ventricular internal diameter at diastole (LVIDd) and
      systole (LVIDs), fractional shortening (FS), ejection fraction (EF) and left
      ventricular mass (LVM) were measured by anatomical M-model echocardiography.
      Infarct size was measured using triphenyl tetrazolium chloride (TTC) staining 1
      week and 8 weeks after the operation. Fibrosis of left ventricular myocardium was
      displayed using Van Gieson staining 1 week after the infarction. In terms of the
      TTC staining results, the left ventricle fell into three categories: infarcted,
      peri-infarcted and remote myocardial regions. Compared with those at baseline and
      in the SHAM group, (1) PRS and PCS in the infarcted, peri-infarcted and remote
      myocardial regions were significantly decreased in the MI group within 1 week
      after the operation (P<0.05) and the low levels lasted 8 weeks; (2) Compared with
      those at baseline, LVIDd, LVIDs, FS, EF and LVM in the MI group showed no
      significant difference 1 week after the operation (P>0.05). However, LVIDd, LVIDs
      and LVM were increased significantly 4 and 8 weeks after the operation (P<0.05),
      and FS and EF were decreased substantially (P<0.05). Van Gieson staining showed
      that fibrosis developed in all the three myocardial regions to varying degrees.
      It is concluded that 2D-STI is non-invasive and can be used to assess regional
      function of myocardium with different blood supply in rats following acute
      occlusion of the LAD, and can be used as a sensitive and reliable means to follow
      up the process of left ventricular remodeling.

PMID- 20037829
TI  - Clinical value of stereoscopic three-dimensional echocardiography in assessment
      of atrial septal defects: feasibility and efficiency.
AB  - Stereoscopic three-dimensional echocardiography(S-3DE) is a novel displaying
      technology based on real-time 3-dimensional echocardiography (RT-3DE). Our study
      was to evaluate the feasibility and efficiency of S-3DE in the diagnosis of
      atrial septal defect (ASD) and its use in the guidance for transcatheter ASD
      occlusion. Twelve patients with secundum ASD underwent RT-3DE examination and 9
      of the 12 were subjected to transcatheter closure of ASD. Stereoscopic vision was
      generated with a high-performance volume renderer with red-green stereoscopic
      glasses. S-3DE was compared with standard RT-3D display for the assessment of the
      shape, size, and the surrounding tissues of ASD and for the guidance of ASD
      occlusion. The appearance rate of coronary sinus and the mean formation time of
      the IVC, SVC were compared. Our results showed that S-3DE could measure the
      diameter of ASD accurately and there was no significant difference in the
      measurements between S-3DE and standard 3D display (2.89+/-0.73 cm vs 2.85+/-0.72
      cm, P>0.05; r=0.96, P<0.05). The appearance of coronary sinus for S-3DE was
      higher as compared with the standard 3D display (93.3% vs 100%). The mean time of
      the IVC, SVC for S-3DE monitor was slightly shorter than that of the standard 3D
      display (11.0+/-3.8 s vs 10.3+/-3.6 s, P>0.05). The mean completion time of
      interventional procedure was shortened with S-3DE display as compared with
      standard 3D display (17.3+/-3.1 min vs 23.0+/-3.9 min, P<0.05). Stereoscopic
      three-dimensional echocardiography could improve the visualization of three
      dimensional echocardiography, facilitate the identification of the adjacent
      structures, decrease the time required for interventional manipulation. It may be
      a feasible, safe, and efficient tool for guiding transcatheter septal occlusion
      or the surgical interventions.

PMID- 20037830
TI  - Quantitative analysis of myocardial perfusion in rabbits by transthoracic real
      time myocardial contrast echocardiography.
AB  - To evaluate the feasibility of real-time myocardial contrast echocardiography
      (RTMCE) by quantitative analysis of myocardial perfusion in rabbits,
      transthoracic RTMCE was performed in 10 healthy rabbits by using continuous
      infusion of SonoVue into the auricular vein. The short axis view at the papillary
      muscle level was obtained. The duration of the time that the contrast took to
      appear in right heart, left heart and myocardium was recorded. The regional
      myocardial signal intensity (SI) versus refilling time plots were fitted to an
      exponential function: y(t) =A(1-e(-beta(t-t0))) + C, where y is SI at any given
      time, A is the SI plateau that reflects myocardial blood volume, and beta is the
      slope of the refilling curve that reflects myocardial microbubble velocity. The
      A, beta and Axbeta values at different infusion rate of SonoVue were analyzed and
      the A, beta and Axbeta values in each segment in the short axis view at the
      papillary muscle level were compared. All the animal experiments were successful
      and high-quality images were obtained. The best intravenous infusion rate for
      SonoVue was 30 mL/h. The contrast appeared in right heart, left heart and
      myocardium at 7.5+/-2.2 s, 9.1+/-2.4 s and 12.2+/-1.6 s respectively. After
      16.6+/-2.3s, myocardial opacification reached a steady state. The mean A, beta
      and Axbeta value in the short axis view at the papillary muscle level were 9.8+/
      3.0 dB, 1.4+/-0.5 s(-1) and 13.5+/-3.6 dBxs(-1) respectively. A, beta and Axbeta
      values showed no significant differences among 6 segments. It was suggested that
      RTMCE was feasible for quantitative analysis of myocardial perfusion in rabbits.
      It provides a non-invasive method to evaluate the myocardial perfusion in rabbit
      disease models.

PMID- 20037832
TI  - Community ecology of the Middle Miocene primates of La Venta,  Colombia: the
      relationship between ecological diversity, divergence  time, and phylogenetic
      richness.
AB  - It has been suggested that the degree of ecological diversity that characterizes
      a primate community correlates positively with both its phylogenetic richness and
      the time since the members of that community diverged (Fleagle and Reed in
      Primate communities. Cambridge University Press, New York, pp 92-115, 1999). It
      is therefore questionable whether or not a community with a relatively recent
      divergence time but high phylogenetic richness would be as ecologically variable
      as a community with similar phylogenetic richness but a more distant divergence
      time. To address this question, the ecological diversity of a fossil primate
      community from La Venta, Colombia, a Middle Miocene platyrrhine community with
      phylogenetic diversity comparable with extant platyrrhine communities but a
      relatively short time since divergence, was compared with that of modern
      Neotropical primate communities. Shearing quotients and molar lengths, which
      together are reliable indicators of diet, for both fossil and extant species were
      plotted against each other to describe the dietary ''ecospace'' occupied by each
      community. Community diversity was calculated as the area of the minimum convex
      polygon encompassing all community members. The diversity of the fossil community
      was then compared with that of extant communities to test whether the fossil
      community was less diverse than extant communities while taking phylogenetic
      richness into account. Results indicate that the La Ventan community was not
      significantly less ecologically diverse than modern communities, supporting the
      idea that ecological diversification occurred along with phylogenetic
      diversification early in platyrrhine evolution.

PMID- 20037833
TI  - Tight perioperative glycemic control using an artificial endocrine pancreas.
AB  - Van den Berghe et al. reported in 2001 that tight glycemic control (maintaining
      blood glucose levels at 80-110 mg/dl) improved morbidity and mortality in the
      surgical intensive care unit. This method was termed intensive insulin therapy
      (IIT), and it is now being adopted worldwide for perioperative care. Recent
      evidence has suggested that perioperative hyperglycemia significantly contributes
      to the development of postoperative infection (POI). Many professional societies
      therefore now recommend IIT over conventional standard glycemic control measures
      for critically ill adult patients to minimize infectious complications. However,
      IIT carries a risk of inducing hypoglycemia, which is linked to serious
      neurological events. We recently demonstrated that achieving perioperative tight
      glycemic control using an artificial endocrine pancreas for surgical patients was
      a safe and effective method for decreasing the incidence of POI without
      increasing the risk of hypoglycemia. We herein review the benefits and
      requirements of tight glycemic control in surgery, with a focus on infection
      control. Strict perioperative glycemic control using a closed-loop artificial
      endocrine pancreas system is recommended for safe and effective performance of
      IIT.

PMID- 20037835
TI  - Could total thyroidectomy become the standard treatment for Graves' disease?
AB  - PURPOSE: Graves' disease is the most frequent cause of hyperthyroidism. Although
      treatment with antithyroid drugs or radioactive iodine is effective, surgery
      remains the preferred treatment for many patients. We analyzed the results of 55
      prospectively followed patients who underwent total thyroidectomy for Graves'
      disease. METHODS: Total thyroidectomy was performed by experienced endocrine
      surgeons in all 55 patients. We monitored the patients postoperatively for early
      and late complications. RESULTS: There were 19 men, with a mean age of 42 years
      (range, 34-68 years) and 36 women, with a mean age of 38 years (range, 19-78
      years). One patient suffered postoperative hemorrhage and subsequent wound
      infection, two patients had transient recurrent laryngeal nerve palsy, and 24
      patients had transient hypocalcemia. The mean follow-up time was 4 years (range,
      10 months to 6 years). Recurrence of hyperthyroidism was not reported in this
      period. CONCLUSION: Removal of all thyroid tissue offers the best chance of
      preventing recurrent hyperthyroidism. Total thyroidectomy is the most effective
      surgery for achieving the goal of treatment of Graves' disease to ensure that
      hyperthyroidism will not recur.

PMID- 20037836
TI  - Surgical management of bronchiectasis: the indications and outcomes.
AB  - PURPOSE: Social limitations in addition to treatment failure, despite preventive
      precautions and aggressive medical treatment, are the main indications for
      surgery in patients with bronchiectasis. The aim of this study was to evaluate
      all aspects of treatment outcomes in surgically treated patients with
      bronchiectasis. METHODS: Ninety-two patients with bronchiectasis treated by a
      surgical resection between January 2002 and June 2007 were included in the study.
      Age, sex, symptoms, etiologic factors, radiological findings, surgical
      procedures, postoperative morbidity and mortality, and hospital stay were
      analyzed. RESULTS: Fifty-four patients were female and 38 were male, with an
      average age of 38.7 (range, 10-67) years, and 84.8% were symptomatic. The
      etiologic factors included frequent infections (37%), childhood infections (22%),
      tuberculosis (12%), foreign bodies (3%), and unknown causes (26%). Ten
      pneumonectomies, 36 lobectomies, 2 bilobectomies, 32 lobectomies and
      segmentectomies, and 12 segmentectomies were performed. The morbidity was 16%,
      the mortality was 1%, and the mean follow-up duration was 15.3 months. Follow-up
      data were obtained in 75 patients of whom 63 (84%) were asymptomatic, 8 (10.7%)
      were symptomatic with clinical improvement, and 4 (5.3%) had had no clinical
      improvement. CONCLUSION: Despite the advances in preventive precautions, medical
      treatment, and follow-up, surgery, with its low mortality and morbidity rates,
      remains a good alternative in selected patients in the treatment of
      bronchiectasis, and fulfills the clinical and social improvement expectations of
      patients.

PMID- 20037834
TI  - Pain following the repair of an abdominal hernia.
AB  - Pain and other types of discomfort are frequent symptoms following the repair of
      an abdominal hernia. After 1 year, the incidence of light to moderate pain
      following inguinal hernia repair is as high as 10% and 2% for severe disabling
      chronic pain. Postoperative chronic pain not only affects the individual patient,
      but may also have a great impact on relatives and society, and may be a cause of
      concern for the responsible surgeon. This paper provides an overview of the
      anatomy, surgical procedures, and disposing factors (age, gender, ethnicity,
      genotype, previous hernia repair, pain prior to surgery, psychosocial
      characteristics, and surgical procedures) related to the postoperative pain
      conditions. Furthermore, the mechanisms for both acute and chronic pain are
      presented. We focus on inguinal hernia repair, which is the most frequent type of
      abdominal hernia surgery that leads to chronic pain. Finally, the paper provides
      an update on the diagnostic and treatment routines for postoperative pain.

PMID- 20037837
TI  - Surgical treatment of intrathoracic hydatid disease: a 5-year experience in an
      endemic region.
AB  - PURPOSE: To present our recent surgical experience in treating patients with
      intrathoracic hydatidosis. METHODS: This study reviewed the files of patients
      with pulmonary/intrathoracic extrapulmonary hydatid cysts treated surgically
      between 2003 and 2009. Demographic, laboratory and radiological data, clinical
      manifestations, site of the cyst, surgical approaches, and final outcome were
      noted and analyzed. RESULTS: Forty patients underwent 42 operations (21 females,
      19 males, mean age 36 years). Thirty-six patients (90%) had pulmonary (56.7% were
      intact/uncomplicated), three (7.5%) had intrathoracic extrapulmonary, and one
      (2.5%) had both pulmonary/intrathoracic extrapulmonary hydatid cysts. The right
      lung was involved in 64.9%. Larger pulmonary cysts ruptured more commonly (P =
      0.007). Most patients (95%) were symptomatic, mostly dyspneic (72.5%). The mean
      forced expiratory volume in 1 s value was significantly reduced in cases with a
      large (P < 0.0001), or ruptured cyst (P = 0.05). The erythrocyte sedimentation
      rate was elevated in case of rupture (P = 0.05). A thoracotomy was performed for
      all patients. A cystotomy and capitonnage was performed more commonly than
      cystotomy without capitonnage for the pulmonary, and total excision was performed
      for the intrathoracic extrapulmonary hydatid cysts. The mortality was 0% and the
      morbidity was 17.5%. All patients received antihelminthic therapy
      postoperatively. There was no recurrence. CONCLUSION: Surgery is considered to be
      the optimal treatment for intrathoracic hydatid disease. In addition, recurrence
      is very low when all such patients receive postoperative antihelminthic therapy.

PMID- 20037838
TI  - Model for end-stage liver disease versus the Child-Pugh score in predicting the
      post-transplant 3-month and 1-year mortality in a cohort of Chinese recipients.
AB  - PURPOSE: This study evaluated the performance of the model for end-stage liver
      disease (MELD) in predicting post-transplant survival in a cohort of Chinese
      patients, and compared its predictive ability with that of the Child-Pugh score.
      METHODS: The study enrolled 117 adult Chinese patients undergoing liver
      transplantation for benign end-stage liver diseases from January 1998 to January
      2007 to evaluate the baseline characteristics and outcomes. RESULTS: In a median
      follow-up duration of 90 weeks (range 0.2-373 weeks), 30 patients died. The 3
      month and 1-year mortality rates of recipients in group 1 (MELD score <28) were
      1.1% and 5.6%, in group 2 (MELD score 28-38) 18.8% and 50.0%, and in group 3
      (MELD score >38) 91.7% and 91.7%, respectively. A statistical difference was
      observed in the mortality rates between the three groups (P < 0.001). At 3
      months, the area under the receiver operating characteristic curve of the MELD
      (0.950) was significantly higher than that of the Child-Pugh score (0.810; P <
      0.05). CONCLUSIONS: Both the MELD and Child-Pugh score are valid models to
      predict the short-term or medium-term outcome of Chinese recipients undergoing
      liver transplantation for benign end-stage liver diseases. The MELD is superior
      to the Child-Pugh score in predicting the 3-month mortality post-transplantation.

PMID- 20037839
TI  - Loss of tissue expression of interleukin-10 promotes the disease progression of
      colorectal carcinoma.
AB  - PURPOSE: Interleukin-10 (IL-10) is a unique cytokine that is thought to be a
      potent immunostimulatory and immunosuppressive factor. The aim of this study was
      to investigate IL-10 expression in colorectal cancer, and clarify its
      relationship to the clinicopathological findings and prognosis. METHODS: Tissue
      samples were collected from 92 patients with colorectal cancer and adjacent
      normal mucosa. The expression of IL-10 in colorectal cancer tissues was evaluated
      by immunohistochemistry. Tissue levels of IL-10 were measured by enzyme-linked
      immunosorbent assay. RESULTS: The mean concentration of IL-10 did not
      significantly differ between the cancer tissue and adjacent normal mucosa. The IL
      10 concentration in cancer tissue with positive staining immunohistochemically
      was significantly higher than that without IL-10 staining. The IL-10 level in
      cancer tissue decreased in accordance with advanced-stage serosal invasion and
      lymph node involvement, and thus predicted poor survival in patients undergoing
      surgery with curative intent. A Cox multivariate analysis demonstrated that a
      decreased IL-10 level in cancer tissue was an independent risk factor for poor
      survival. CONCLUSION: The tumor IL-10 level in colorectal cancer was inversely
      correlated with serosal invasion and lymph node metastasis, which thus reflected
      tumor progression. Evaluating the tumor expression of IL-10 may therefore provide
      valuable information for predicting the long-term survival in patients undergoing
      surgery with curative intent.

PMID- 20037840
TI  - Endovascular treatment of an aortobronchial fistula caused by a distal aortic
      arch mycotic aneurysm: report of a case.
AB  - We report a case of an aortobronchial fistula causing massive hemoptysis, which
      was managed by emergency stent grafting. Although this procedure was successful
      initially, the aortobronchial fistula appeared again 7 months later.
      Aneurysmectomy, followed by rifampicin-soaked gelatin sealed polyester graft
      replacement and omentopexy, was performed under cardiopulmonary bypass. The
      patient, a 73-year-old woman, had an uneventful postoperative course and the
      infection was eradicated.

PMID- 20037841
TI  - Beating-heart totally endoscopic coronary artery bypass grafting: report of a
      case.
AB  - This case report presents beating-heart totally endoscopic coronary artery bypass
      grafting (TECAB) for single-vessel coronary artery disease. A 72-year-old man
      with isolated left anterior descending (LAD) coronary artery disease was
      considered eligible for TECAB. Left internal thoracic artery (LITA) mobilization
      and subsequent off-pump revascularization applying the LITA to the LAD in a
      closed chest environment was performed using the da Vinci surgical system
      (Intuitive Surgical, Mountain View, CA, USA). The LITA was first harvested
      completely in a totally skeletonized fashion through three incisions 1-2 cm long
      in the left thoracic wall. The LAD was immobilized with the aid of a heart
      stabilizer. The LITA was then anastomosed to the LAD with 10 interrupted sutures
      of a Nitinol self-closing S15 U-clip device (Medtronic, Minneapolis, MN, USA) on
      the beating heart without the use of cardiopulmonary bypass. The time acquired to
      perform anastomosis was 20 min, and the total operative time was 5 h 34 min. The
      postoperative course was uneventful and the patient was discharged 5 days after
      the operation. Beating-heart TECAB was successfully performed for this patient
      with single-vessel LAD disease. This approach may be an evolutionary step toward
      beating-heart multivessel TECAB.

PMID- 20037842
TI  - Solitary splenic metastasis from early gastric cancer: report of a case.
AB  - Solitary metastasis of a malignancy to the spleen is rare. We herein describe a
      case of splenic metastasis from early gastric cancer. A 76-year-old man underwent
      an endoscopic mucosal resection (EMR) for early gastric carcinoma in the cardia.
      Pathologically, the tumor showed invasion into the submucosal layer, and the
      stump of the surgical specimen appeared to be positive for malignant cells. He
      thus underwent a proximal gastrectomy with nodal dissection. One year later,
      serum carcinoembryonic antigen was elevated, and a splenic mass was detected by
      computed tomography and ultrasonography. Because the tumor increased in size very
      gradually and no metastatic lesions were detected at the other sites, we
      performed a splenectomy. The lesion was pathologically diagnosed as metastasis
      from the previous gastric carcinoma, and the patient remains healthy to date
      without recurrence, more than 2 years after the splenectomy. When solitary
      metastasis to the spleen is suspected during the postoperative follow-up of a
      patient with gastric cancer, a splenectomy is a potentially effective treatment.

PMID- 20037843
TI  - Laparoscopy-assisted distal gastrectomy for early gastric cancer with complete
      situs inversus: report of a case.
AB  - We herein report our experience in performing a laparoscopy-assisted distal
      gastrectomy involving standard lymph node dissection for a patient with early
      gastric cancer and situs inversus. A superficial elevated lesion was found on the
      posterior wall of the antrum. The preoperative diagnosis was cStage IA (cT1, cN0,
      cH0, cP0, cM0). A laparoscopy-assisted distal gastrectomy with standard lymph
      node dissection (D1 + beta) for early gastric cancer was successfully performed
      by shifting the monitor to the right and left, and by applying sufficient care
      and time. The course of blood vessels was not abnormal except for the right/left
      inversion. Billroth I reconstruction was performed through a delta-shaped
      anastomosis. The postoperative course was favorable and the patient was
      discharged on postoperative day 12. Based on a histopathological examination, a
      5.0 x 5.0-cm, mucosal, poorly differentiated adenocarcinoma (pT1, pN0, sH0, sP0,
      sM0, Stage IA) was diagnosed.

PMID- 20037844
TI  - Splenic rupture as a complication of colonoscopy: report of a case.
AB  - Colonoscopy is a common procedure with the rare complication of a splenic injury.
      The proposed mechanism of injury is excessive splenocolic ligament traction. The
      diagnosis is made by computed tomography and the treatment is determined by the
      patient's stability. Here we report a case of splenic injury during colonoscopy
      with failure to manage conservatively. A review of the literature and suggested
      guidelines are also provided.

PMID- 20037845
TI  - Laparoscopic resection of an epidermoid cyst originating from an intrapancreatic
      accessory spleen: report of a case.
AB  - A 67-year-old man underwent an investigation of epigastric pain and weight loss.
      Preoperative imaging findings suggested the presence of a tumor, which developed
      as an epidermoid cyst and originated from an intrapancreatic accessory spleen;
      however, the possibility of malignancy could not be ruled out. We therefore
      performed a laparoscopic-assisted distal pancreatectomy with a splenectomy for
      both diagnostic and treatment purposes. Five laparoscopic ports were created.
      After the spleen and pancreatic tail were dissected from the retroperitoneum
      laparoscopically, they were pulled out through a 7-cm left subcostal incision and
      resected with an endoscopic linear stapler. The operative time was 227 min and
      the blood loss was 400 ml. The postoperative course was uneventful. The final
      pathological diagnosis was in agreement with the preoperative diagnosis. This
      case demonstrates that the minimally invasive approach of laparoscopic surgery
      can be used safely and successfully for difficult-to-diagnose pancreatic tumors.
      This is the first report describing a laparoscopic resection of an epidermoid
      cyst originating from an intrapancreatic accessory spleen.

PMID- 20037846
TI  - Utility of preoperative dynamic magnetic resonance imaging of the pancreas in
      diagnosing tumor-forming pancreatitis that mimics pancreatic cancer: report of a
      case.
AB  - The differential diagnosis of pancreatic carcinoma and tumor-forming pancreatitis
      remains difficult, and this situation can cause serious problems because the
      management and prognosis of these two focal pancreatic masses are entirely
      different. We herein report a case of tumor-forming pancreatitis that mimics
      pancreatic carcinoma in an 80-year-old woman. Computed tomography showed a solid
      mass in the head of the pancreas, and endoscopic retrograde
      cholangiopancreatography showed a complete obstruction of the main pancreatic
      duct in the head of the pancreas. Dynamic contrastenhanced magnetic resonance
      imaging (MRI) demonstrated a time-signal intensity curve (TIC) with a slow rise
      to a peak (1 min after the administration of the contrast material), followed by
      a slow decline at the pancreatic mass, indicating a fibrotic pancreas. Under the
      diagnosis of tumor-forming pancreatitis, the patient underwent a segmental
      pancreatectomy instead of a pancreaticoduodenectomy. The histopathology of the
      pancreatic mass was chronic pancreatitis without malignancy. The pancreatic TIC
      obtained from dynamiccontrast MRI can be helpful to differentiate tumor-forming
      pancreatitis from pancreatic carcinoma and to avoid any unnecessary major
      pancreatic surgery.

PMID- 20037847
TI  - Perioperative challenges associated with a pancreaticoduodenectomy and distal
      pancreatectomy for pancreatic cancer in patients with situs inversus totalis:
      report of two cases.
AB  - Situs inversus totalis is a rare anatomic variant of a complete mirror-image
      transposition of the thoracic and abdominal viscera. The performance of a
      pancreaticoduodenectomy and distal pancreatectomy in patients with situs inversus
      totalis is both rare and challenging. We herein present two cases of pancreatic
      cancer with situs inversus totalis. The abdominal anatomy was preoperatively
      assessed by multidetectorrow computed tomography, three-dimensional
      reconstruction, and angiography. We herein report that a pancreaticoduodenectomy
      and distal pancreatectomy with standard regional lymphadenectomy are feasible in
      patients with situs inversus totalis. Due to the transposition of the viscera and
      major blood vessels in such cases, preoperative knowledge of the exact anatomy,
      mapping of anomalies, and meticulous forward planning are essential for
      performing these technically difficult and complex hepatobiliary-pancreatic
      surgeries.

PMID- 20037848
TI  - Mesenchymal hamartoma of the liver originating in the caudate lobe with
      t(11;19)(q13;q13.4): report of a case.
AB  - We herein report the case of a 35-month-old female child presenting with
      mesenchymal hamartoma of the liver (MHL), with t(11;19)(q13;q13.4) originating in
      the caudate lobe. This case is the eighth known description of a cytogenetic
      abnormality in mesenchymal hamartoma of the liver. It is similar to the seven
      cases previously reported, in that one of the breakpoints involves the chromosome
      band 19q13.3 or 19q13.4, but it is the first report of an abnormality originating
      in the caudate lobe.

PMID- 20037849
TI  - Laparoscopic primary repair of ventral hernias: early results of a new technique.
AB  - Epigastric, umbilical, incisional, parastomal, and trocar site hernias are all
      classified as "ventral" hernias, which constitute a great portion of the surgery
      in a general surgical practice, and debate still continues regarding the optimal
      surgical strategy to correct these anatomical defects. Although repairing these
      hernias using a synthetic material, whether placed open or laparoscopically, has
      gained wide popularity, there are some situations where the use of a mesh is
      either unnecessary or contraindicated. This article presents the cases of 10
      patients with some kind of ventral hernia which were all repaired
      laparoscopically with a primary suturing technique.

PMID- 20037850
TI  - Does hepatic adult capillary hemangioma exist?

PMID- 20037851
TI  - Evaluation of thyroid hormone levels and somatomedin-C (IGF-1) in patients with
      chronic obstructive pulmonary disease (COPD) and relation with the severity of
      the disease.
AB  - Chronic obstructive pulmonary disease (COPD) has recently become a significant
      cause of mortality and morbidity. In the present study, we aimed to investigate
      the relationship between the severity of the disease and levels of serum thyroid
      hormones and somatomedin-C [Insulin-Like Growth Factor (IGF-1)]. Sixty one COPD
      cases (group 1) were enrolled. Control group (group 2) consisted of 20 healthy
      individuals. Blood samples were obtained for the analysis of arterial blood gases
      and hormone levels and respiratory function tests were performed on the same day.
      Measured hormone levels were compared between group 1 and group 2. Among thyroid
      hormone levels, there was no significant difference in thyroid stimulating
      hormone and free T3 between group 1 and 2 whereas free T4 levels were
      significantly higher in group 1 (p< 0.01). Additionally, mean IGF-1 levels were
      significantly lower in group 1 (p< 0.005). When three groups, classified
      according to Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      criteria, were compared, significant differences were observed between mild
      moderate COPD cases and severe patients with respect to free T3 and IGF-1 levels
      (p< 0.05). Hormone levels in COPD patients change depending on the severity of
      the disease. In the future hormone therapies can use for the COPD treatments.
      Further studies with larger sample sizes are required to confirm our conclusions.

PMID- 20037852
TI  - Clinical significance of lung perfusion defects in children with post-infectious
      bronchiolitis obliterans.
AB  - Clinical significance of segmental lung perfusion defects in children with
      bronchiolitis obliterans (BO), have not been reported before. The aim of this
      study was to evaluate clinical significance of lung perfusion defects in children
      with BO and to reveal its impact on follow up. The study included 38 children
      aged 9 to 60 months (17.8 + or - 13.4 months) with BO. Diagnosis was based on
      persistent respiratory findings beyond six weeks and oligemic-mosaic pattern in
      lung high resolution computerized tomography. Chest X-ray, 24 hour esophageal pH
      monitoring, sweat chloride test, immunoglobulin levels and respiratory viral
      screening were carried out in all. Lung perfusion scintigraphy was carried out at
      least three months after the first clinical sign of BO. Perfusion defects were
      scored. Scintigraphy demonstrated perfusion defects in 24 (63.2%) patients but
      was normal in 14 (36.8%). Number of segments having perfusion defects was 2.9 +
      or - 2.6. Mean number of exacerbations and days of hospitalization during the
      first year of follow up were 4.7 + or - 4.4 and 26.9 + or - 29.8 respectively. It
      was detected that number of perfusion defects correlated significantly with the
      number of exacerbations and duration of hospitalization (r= 0.66 and p= 0.00). In
      conclusion, number and extent of segments with perfusion defects in lungs of
      children with BO are correlated with clinical severity. Therefore, evaluation of
      lung perfusion status may aid in clinical determination of disease severity and
      its follow-up.

PMID- 20037853
TI  - The treatment results of patients with multidrug resistant tuberculosis and
      factors affecting treatment outcome.
AB  - The treatment of multi-drug resistant tuberculosis (MDR-TB) is complicated and
      results are not always satisfactory. We aimed to investigate treatment results of
      our patients, relapse rates, factors affecting treatment outcome. We evaluated
      prospectively, 142 patients, who had been hospitalised with diagnosis of MDR-TB
      in our clinic between January 1995-December 2000 at Sureyyapasa Chest Diseases
      and Chest Surgery Training and Research Hospital in Istanbul, Turkey. All
      patients were male and human immunodeficiency virus negative. The mean age was 39
      + or - 11 (16-65) years. A mean number of 5.5 + or - 0.8 (4-8) second line drugs,
      including one parenteral drug, were administered. Of 142 patients, 102 (71.8%)
      were classified as cured, 16 (11.3%) patients were defaulters, failure was seen
      in 10 (7.0%) patients and 14 (9.9%) patients died during treatment. Surgical
      resection was applied in 35 patients and cure was achieved in 88.5% of them. Of
      102 patients who were cured, 89 (87.2%) were available for follow up and mean
      duration of follow up was 19.2 + or - 10.3 (12-72) months. Relapse was not
      detected in any of them. Patients with unsuccessful outcomes had a higher
      incidence and higher mean number of second-line drugs usage in previous regimens,
      higher incidence of antecedent prothionamide and ofloxacin usage, higher
      incidence of extensive radiologic involvement and withdrawal of responsible drugs
      due to adverse effects. Limited radiologic involvement, non-usage of antecedent
      prothionamide and adjuvant surgery were found as significant independent factors
      effecting successful treatment outcome. MDR-TB is a complex but a treatable
      disease. To know much more about the factors effecting treatment results and to
      arrange the proper conditions, are expected to make increases in the success
      rates of MDR-TB treatment.

PMID- 20037854
TI  - [Severity scores and factors related with mortality in cases with community
      acquired pneumonia patients in intensive care unit].
AB  - Totally 48 cases with diagnosed as community-acquired pneumonia who were treated
      in intensive care units of two different university hospital included to the
      study. The mean age of cases was 67.8, 29 were males and 19 females. Glasgow Coma
      Score (GCS), Acute Physiology Assesment and Chronic Health Evaluation II (APACHE
      II), Pneumonia Severity Index (PSI) and Sequential Organ Failure Assessment Score
      (SOFA) of 46 cases were determined. The most common comorbid disease was
      cerebrovascular disease. We determined that microbiological tests were made in 30
      cases and pathogen agent was established in 7 cases of them. The mean lenght of
      stay in hospital and intensive care unit were 16.1 days and 8.8 days
      respectively. The mean GCS was 11.4, the mean PSI was 130.7 and 38 cases were in
      high risk classes. The mean APACHE II and SOFA scores were 20.7 and 4.4
      respectively. We determined that hypotension and intubation increased the
      mortality risk. The mean blood urea nitrogen, %PNL and respiratory rate were
      higher in cases who were died. The mortality rate in group 3b and group 4 were
      respectively 41.2% and 44.0%. Totally 20 (41.7%) cases died.

PMID- 20037855
TI  - [Vocal cord functions in patients with asthma attack].
AB  - This study was planned to evaluate vocal cord functions and to establish
      underlying vocal cord dysfunctions (VCD) in patients with asthma attack. All
      patients admitted to emergency service of our hospital with asthma attack between
      February 01, 2007 and June 01, 2007 were included in the evaluation. After the
      evaluation, all patients regarded to have asthma attacks based on GINA 2006 guide
      were enrolled in the study. After first intervention, patients underwent
      endoscopic larynx examination for the evaluation of vocal cord functions. Twenty
      four (65.7%) male and 11 female (31.4%), overall 35 patients diagnosed with
      asthma and who did not have the history of another disease were included in the
      study. At endoscopic larynx examination carried out after first medical
      examination, at the moment of asthma attack, tongue, tongue base, epiglottis and
      arytenoid were observed to be within normal limits. In 9 (25.7%) patients, upper
      respiratory tract was hyperemic and in 2 (5.7%) odematous. One patient had nasal
      polyposis (p> 0.05). In the evaluation of vocal cord functions, restriction in
      adduction was observed in merely one patient. All other functions were normal.
      Rima opening width was established to be mean 8.34 + or - 0.725. VCD was deteced
      in none of the patients included in the study. Although we did not detect VCD in
      any patient, VCD should be borne in mind in cases which presents with the
      clinical picture of asthma and responds weakly to the treatment or in cases of
      unexplained shortness of breath. This may prevent many unnecessary procedures
      such as medication, entubation, tracheostomy and iatrogenic mortality. Further
      longutudial studies are required in order to shed light on the assocation of
      asthma with VCD.

PMID- 20037856
TI  - Value of endobronchial ultrasound in staging non-small cell lung cancer.
AB  - Endobronchial ultrasound guided fine-needle aspiration (EBUS-TBNA) is an
      accurate, safe and minimally invasive technique for the analysis of mediastinal
      lymph nodes. The aim of our study was to assess the value of EBUS probe using
      single-channel bronchoscope. Twenty-two patients who undervent EBUS-TBNA with
      proven non-small cell lung cancer and enlarged (> 1 cm) mediastinal lymph node at
      chest computed tomography were retrospectively enrolled in the study. The mean
      age of the patients was 56.8 + or - 9.0 (45-76), and all of them were men. Mean
      size of sampled 32 lymph nodes was 19.9 + or - 6.5 mm (10-30). The average number
      of needle passes was 3.2 + or - 0.9 (1-5). Adequate material was found in 31
      (97%) of the lymph nodes. In 15 (68.1%) of the patients lymph node metastasis was
      detected. Of 7 patients with negative cytology, a mediastinoscopy was done. There
      were no complications other than minimal hemorrhage. The sensitivity of EBUS-TBNA
      was calculated as 88.2%, whereas the specificity was 100% and accuracy was found
      to be 90.9%. EBUS guided TBNA of mediastinal lymph nodes is a safe approach which
      can be a tool for obtaining adequate material and high diagnostic yield in
      staging of non-small cell lung cancer.

PMID- 20037857
TI  - [Jeune syndrome (asphyxiating thoracic dystrophy): a case report].
AB  - Jeune syndrome or asphyxiating thoracic dystrophy is a rare autosomal recessive
      skeletal dysplasia characterized by a small thorax, short-limbed dwarfism, renal
      and hepatic anomalies. It is estimated to occur in 1 per 100.000-130.000 live
      births. Radiological confirmation of diagnosis is essential. Prognosis of the
      disease is due to the severity of chest deformities and most of the patients are
      lost in their first year because of respiratory problems. We presented a 19-month
      old female patient who admitted to our clinic because of recurrent lower
      respiratory tract infections and diagnosed as Jeune syndrome and reported due to
      its rarity.

PMID- 20037858
TI  - Nodular lymphoid hyperplasia of the lung: the role of positron emission
      tomography in diagnosis.
AB  - Pulmonary nodular lymphoid hyperplasia (NLH) is defined as reactive lymphoid
      proliferation forming solitary or multiple nodules or localized infiltrates
      localized in the lungs. Radiological presentations are generally solitary or
      multiple nodules, but air bronchograms and ground glass attenuation may be
      present. Patients mostly asymptomatic and the lesions were detected
      coincidentally on routine chest X-rays. We present a case of NLH with cavitary
      lesion arising in the lung of a 61 year-old man who admitted with cough and
      massive hemoptysis. The lesion had positive fluorodeoxyglucose (FDG) uptake. To
      our knowledge, this is the only patient reported in the literature presenting
      with massive hemoptysis and a cavitary lesion with positive FDG uptake.

PMID- 20037859
TI  - Is tin fume exposure benign or not? Two case reports.
AB  - Stannosis is a non-fibrotic form of pneumoconiosis in which tin-oxide is
      accumulated in pulmonary parenchyma as a result of inhalation of tin-oxide
      (stannic oxide) dust and fume. Chest radiograph shows numerous small very dense
      nodules in both lungs. Although radiological findings of stannosis were apparent,
      the patients were clinically in good condition, and pulmonary function test (PFT)
      values showed no disability. Case 1, 70-year-old man had exercise dyspnea for
      four years. He worked as a tinner for 40 years. A slight restriction was detected
      in his PFT. Diffused, small, dense, reticulonodular opacities were detected on
      chest X-ray. Thorax high resolution computerized tomography (HRCT) revealed
      dense, common noduler lesions, reticulation and honeycomb appearance. Case 2, the
      patient was a 50-year-old woman. She had been exposed tin fume for 33 years and
      never smoked. In PFT, a slightly low FEV1 value and a normal FVC value were
      detected. Diffused reticulonodular opacities were detected on chest X-ray. On
      thorax HRCT, ground glass densities in some areas, widespread interlobulary
      septal thickening, peribronchial thickening predominant in perihilar regions in
      both lungs and subpleural milimetric nodular densities were observed in the upper
      and middle lobe of the right lung. Two patients who exposed to tin fume are
      described. However, contrary to what is expected, both patients clinically
      deterioted and died as a result of respiratory failure.

PMID- 20037860
TI  - Treatment of endoluminal typical carcinoid tumor with bronchoscopic techniques.
AB  - Surgical treatment of typical bronchial carcinoid tumors varies from bronkoskopic
      excision to major resective procedures. Typical carcinoid tumor was detected in
      29 year old man patient who were admitted to our clinic with hemoptysis and
      dyspnea. Typical carcinoid tumor was treated with exsicion after argon plasma
      coagulation by bronchoscopic techniques. It should not be forgotten that
      bronchoscopic approach and simple excision is an effective and safe procedure for
      the treatment of typical bronchial carcinoid tumors in selected cases like
      polypoid type lesions.

PMID- 20037861
TI  - Oddi sphincter fibrosis due to chemotherapy agents in small cell lung cancer:
      case report.
AB  - A 62-year-old, man patient was diagnosed as small cell lung cancer. Cisplatin (80
      mg/m(2), first day) and etoposide (100 mg/m(2), three days) chemotherapy was
      started for once 21 days. As the patient received third course of chemotherapy,
      jaundice and hyperbilirubinemia were detected. Hepatic ultrasonography showed
      dilated choledochus and intrahepatic biliary tract. Hepatic markers and serologic
      tests for viral hepatitis were found as normal. Finally endoscopic retrograde
      cholangiopancreatography (ERCP) was performed. Endoscopic sphincterotomy was
      performed in the first ERCP and two days later, second ERCP was performed and
      oddi sphincter was seen as fibrotic and stenotic and stent was placed. One day
      after the stent placement, direct bilirubin was found as 6.2 mg/dL and 10 days
      later laboratory parameters were detected as normal. Oddi sphincter fibrosis
      occurred due to lung cancer chemotherapy treatment is an interesting case for
      fibrosis not having been reported due to cisplatin or etoposide before.

PMID- 20037862
TI  - Giant bulla mimicking tension pneumothorax.
AB  - In the chest X-ray, we observe tension pneumothorax (TPX) as wide radiolucent
      view in a hemithorax and pushing the mediastinal structures contralateral. Giant
      bulla may mimic TPX with wide radiolucent view and mediastinal shift. The present
      report includes giant pulmonary bulla in 35-year-old woman. The giant bulla was
      diagnosed as a TPX in emergency, and chest tube was performed. The
      differentiation between TPX and a giant bulla may be very difficult. The
      therapies of these two similar entities are completely different. So that, we
      must be careful about anamnesis, physical examination and radiology for true
      diagnosis.

PMID- 20037863
TI  - The WHO global alliance against chronic respiratory diseases in Turkey (GARD
      Turkey).
AB  - In order to prevent and control non-communicable diseases (NCDs), the 61st World
      Health Assembly has endorsed an NCD action plan (WHA resolution 61.14). A package
      for essential NCDs including chronic respiratory diseases (CRDs) has also been
      developed. The Global Alliance against Chronic Respiratory Diseases (GARD) is a
      new but rapidly developing voluntary alliance that is assisting World Health
      Organization (WHO) in the task of addressing NCDs at country level. The GARD
      approach was initiated in 2006. GARD Turkey is the first comprehensive programme
      developed by a government with all stakeholders of the country. This paper
      provides a summary of indicators of the prevalence and severity of chronic
      respiratory diseases in Turkey and the formation of GARD Turkey.

PMID- 20037864
TI  - [Patient-ventilator interaction].
AB  - Mechanically ventilated patients interact with ventilator functions at different
      levels such as triggering of the ventilator, pressurization and cycling from
      inspiration to expiration. Patient ventilator asynchrony in any one of these
      phase results in fighting with ventilator, increase in work of breathing and
      respiratory muscle fatigue. Patient ventilator dyssynchrony occurs when gas
      delivery from the ventilator does not match with the neural output of the
      respiratory center. The clinical findings of patient-ventilator asynchrony are;
      use of accessory respiratory muscle, tachypnea, tachycardia, active expiration,
      diaphoresis and observation of asynchrony between patient respiratory effort and
      the ventilator waveforms. Among the patients with dynamic hyperinflation such as
      chronic obstructive pulmonary disease the most frequent causes of patient
      ventilator asynchrony are trigger and expiratory asynchronies. In acute
      respiratory distress syndrome patient-ventilator asynchrony may develop due to
      problems in triggering or asynchrony in flow and inspiration-expiration cycle.
      Patient-ventilator interaction during noninvasive mechanical ventilation may be
      affected by the type of masks used, ventilator types, ventilation modes and
      parameters, humidification and sedation. Among the different patient groups it is
      important to know causes and solutions of patient-ventilator asynchrony problems.
      By this way patient will adapt ventilator and then dyspnea, ineffective
      respiratory effort and work of breathing may decrease subsequently.

PMID- 20037865
TI  - [Pulmonary thromboembolism based on the Turkish national data].
AB  - Pulmonary thromboembolism (PTE) is an important health problem. It is disease
      with a wide clinical spectrum, from asymptomatic small PTE to life threatening
      major PTE. In this manuscript, we evaluated studies performed in Turkey to
      determine national status about PTE. We were examined that published in national
      or international journals, or abstracts presented in congresses from 1991 to
      nowadays, excluding reviews or case studies. Among the 75 studies, performed in
      Turkey, related this topic, the most common complaints in PTE were dyspnea and
      chest pain. Surgery and immobilization were the most frequent risk factors
      causing PTE, however cancers were rarely reported as a risk factor. The most
      common findings of chest radiography were parenchymal infiltration and pleural
      effusion. While the diagnosis of PTE were mostly based on clinical findings and
      lung scan findings in the earlier studies, spiral thorax computed tomography
      became an important tool of diagnosis recently, specially after the years of
      2000. Interesting, mortality rates in massive PTE were found lower than the
      literature. In conclusion, the number of patients with PTE is increased due to
      developments in the diagnosis of PTE. Our national findings commonly comply with
      the international literature. However, we think the documentation of current
      national status in PTE requires more comprehensive studies.

PMID- 20037866
TI  - Positron emission tomography findings in rounded atelectasis.

PMID- 20037867
TI  - Novel use of Lodox Statscan in a level one trauma center.
AB  - Trauma continues to be a large source of poor outcomes for patients in the United
      States. While clinical guise is very important in the acute setting, objective
      physical data is becoming increasingly important in the diagnosis of many
      injuries sustained during trauma. Radiography has always been the primary
      diagnostic modality applied in trauma situations but it continues to be a time
      consuming and unwieldy part of the acute resuscitation of the patient. The novel
      use of the Lodox Statscan (Lodox Systems (Pty), Ltd., Benmore, South Africa), a
      type of digital radiography, as a means to help combat these problems was
      evaluated at Creighton University Medical Center, Omaha, Nebraska. This new
      machine uses a linear beam technology to scan the entire body in 13 seconds.
      Here, we describe this digital radiography system, its introductory use in the
      trauma bay, and discuss cases where it has proven valuable. Based upon our
      preliminary experience, the use of the device in large centers shows promise for
      improving morbidity and mortality outcomes in trauma patients.

PMID- 20037868
TI  - [The role of apoptosis and protective effect of carnitine in contralateral
      testicular injury in experimental unilateral testicular torsion].
AB  - BACKGROUND: We examined the role of programmed cell death (PCD) in the etiology
      of contralateral testis injury as well as the protective effect of carnitine.
      METHODS: Thirty-six Wistar Albino rats were used in the study. Rats were divided
      into six groups as control, sham, torsion-detorsion with 6- and 24-hour
      intervals, and torsion-detorsion-carnitine administration with 6- and 24-hour
      intervals. The left testes of all rats were torsioned 720 degrees.
      Intraperitoneal carnitine was administered to groups as 100 mg/kg one hour before
      detorsion. Orchiectomy was applied to the contralateral testis a week after
      detorsion. Testes were examined with respect to diameters of seminiferous tubules
      (DST), ratios of malonyl dialdehyde and Johnsen biopsy scores (JBS), and PCD
      ratios. Results were evaluated by ANOVA test. RESULTS: Programmed cell death
      ratios were significantly higher in the torsion-detorsion with 6- and 24-hour
      intervals groups compared to the sham group. Those increases were more prominent
      in the torsion-detorsion with 24-hour interval group. DST and JBS of the control
      group were significantly higher than in the experimental groups (p < 0.05). The
      protective effect of carnitine was significant in the 24-hour torsion group,
      while no significant difference were detected in the 6-hour torsion-detorsion
      carnitine group. CONCLUSION: Increased injury and PCD in the contralateral testis
      was observed with prolonged exposure time in this model. It was possible to
      decrease the injury with carnitine.

PMID- 20037869
TI  - Comparison of cyanoacrylate-assisted arteriotomy closure with conventional
      closure technique.
AB  - BACKGROUND: We aimed to compare conventional suture closure of arteriotomy with N
      butyl-cyanoacrylate-assisted suture closure. METHODS: Forty Wistar rats were
      randomly divided into two groups. Standard arteriotomy was performed to the
      abdominal aorta through a midline incision. In the first group, arteriotomy was
      closed by 3 stitches with 45 degrees between each and in the second by two
      stitches with 0.1 ml (12-12.5 mg) cyanoacrylate. Amount of blood loss, operation
      time and severity of myointimal hyperplasia by immunohistochemistry on aorta
      segments were measured on postoperative days 7 and 30. RESULTS: Mean anastomotic
      time was 13.5 +/- 1.64 in the first and 13.0 +/- 1.75 min in the second group (p
      = 0.356). Operation time was 23.45 +/- 3.63 in the control and 21.0 +/- 3.09 min
      in the second group (p = 0.027). Mean amount of bleeding was 473.75 +/- 260.5 in
      the first and 327.5 +/- 155.36 microl in the second group (p = 0.037). Intimal
      thickness on the 7th day was 80.62 +/- 7.92 in the first and 83.24 +/- 3.42
      microm in the second group, and on the 30th day was 81.64 +/- 5.11 in the first
      and 88.77 +/- 11.03 microm in the second group. The early and late intimal
      thicknesses were similar (p = 0.35 and 0.87, respectively). CONCLUSION:
      Reconstruction of arteriotomies with fewer sutures in combination with
      cyanoacrylate is a safe method associated with less blood loss and shorter
      operation time. It also does not lead to increased myointimal hyperplasia.

PMID- 20037870
TI  - The influence of omentectomy on bacterial clearance: an experimental study.
AB  - BACKGROUND: The influence of an omentectomy on peritoneal defense mechanisms and
      its clinical consequences have not been fully elucidated. In the present study,
      we aimed to investigate the influence of omentectomy on bacterial growth in blood
      and tissue specimen cultures in rats with experimental peritonitis. METHODS:
      Fifty Wistar-Albino rats were included in the present study. Animals were
      assigned into five groups as follow: Group 1 (n = 10), omentectomy alone; Group 2
      (n = 10), omentectomy + bacterial peritonitis; Group 3 (n = 10), bacterial
      peritonitis alone; Group 4 (n = 10), laparotomy alone; and Group 5 (n = 10), sham
      group. Culture positivity rate and bacterial growth (colony forming units
      [CFU]/gram tissue) were assessed in mesenteric lymphoid tissue and venous blood
      of all animals. RESULTS: Bacterial growth in lymphoid tissue was significantly
      higher in Groups 2 and 3 than others (both, p < 0.05). CFU of Escherichia coli in
      lymphoid tissue was significantly higher in Group 2 than in Groups 1 and 3 (both,
      p < 0.05/4). Blood culture positivity was significantly higher in Group 2 than
      the others (both, p < 0.05). CONCLUSION: The omentum has an important role in the
      host peritoneal defense system. Peritoneal infection may pursue a more severe
      course with increased bacterial entrance into the blood in the absence of the
      omentum.

PMID- 20037871
TI  - The effect of blood albumin and total lymphocyte count on short-term results in
      elderly patients with hip fractures.
AB  - BACKGROUND: A study was performed to determine the effects of blood albumin and
      total lymphocyte count on the postoperative one-year period in 74 elderly hip
      fracture patients. METHODS: In 2006, 74 patients (52 female, 22 male) with hip
      fracture who were 65 years of age or older were included in the study. Admission
      albumin levels and total lymphocyte counts were recorded. The outcomes examined
      were mortality, length of hospital stay and ambulatory ability. Ambulatory
      ability was assessed according to Parkland and Palmer criteria. RESULTS: There
      were 61 patients aged 65-84 years, and 13 patients aged 85-105 years. Forty-one
      patients (55.4%) had hypoalbuminemia and 23 patients (31.1%) had low total
      lymphocyte count. Low albumin and total lymphocyte counts were associated with
      higher mortality (p = 0.011). Patients with low albumin levels had longer length
      of hospital stay (p = 0.002). Patients with normal albumin and total lymphocyte
      counts had higher mobility score meaning better function (p = 0.012).
      Multivariate analysis yielded that low total lymphocyte count, American Society
      of Anesthesiologists (ASA) 3-4 and female gender remained significant independent
      predictors of one-year mortality. No single blood parameter was found to be
      effective on ambulatory status. CONCLUSION: Risk of mortality in elderly hip
      fracture patients increases with female gender, ASA 3-4 and low total lymphocyte
      counts. Hypoalbuminemia is associated with longer hospitalization. Identification
      of these risk factors can help in the case management for a more favorable
      outcome.

PMID- 20037872
TI  - External fixation followed by delayed interlocking intramedullary nailing in high
      velocity gunshot wounds of the femur.
AB  - BACKGROUND: High velocity gunshot-related fracture is associated with massive
      soft tissue damage and severe comminution at the fracture site. This unique type
      of open fracture presents a serious challenge to the orthopedic traumatologist.
      METHODS: The study was conducted prospectively involving patients who presented
      to the Accident and Emergency Department of the Bone and Joint Surgery Hospital
      Srinagar (India), from January 2005 to March 2007, with a history of high
      velocity gunshot wounds to the femur. Initial stabilization with external
      fixation was followed by delayed interlocking intramedullary nailing. The
      patients were followed for an average period of 26 months (range, 15-39 months).
      RESULTS: All the patients were males, with an average age of 37 years (range, 22
      52 years). Twenty-four (65%) were type IIIA, 11 (30%) were type IIIB and 2 (5%)
      were type IIIC. All the fractures united in good alignment in an average time of
      24 weeks. CONCLUSION: External fixation as a primary modality of treatment
      provides more than adequate stabilization to facilitate nursing, good wound care
      and physiotherapy. A staged protocol of primary temporary fixation by unilateral
      external fixation followed by delayed reamed intramedullary interlocking nail
      seems to be an effective method of treatment for high energy gunshot femoral
      fractures.

PMID- 20037873
TI  - Comparison of trauma scoring systems for predicting mortality in firearm
      injuries.
AB  - BACKGROUND: Prediction of mortality in trauma patients is an important part of
      trauma care. Trauma scoring systems are the current methods used for prediction
      of mortality. We aimed to evaluate and compare the performances of Injury
      Severity Score (ISS) and New Injury Severity Score (NISS) in firearm injuries.
      METHODS: Records of 135 firearm-injured patients who applied to Uludag University
      Emergency Department between January 2001 and December 2005 were analyzed
      retrospectively. All patients' data, including age, gender, cause of injury,
      initial vital signs, injury region, Glasgow Coma Scale (GCS), Revised Trauma
      Score (RTS), mortality, operation data, and final diagnosis, were collected, and
      ISS, NISS and Trauma and Injury Severity Score (TRISS) were calculated. RESULTS:
      Mortality rate was 12.6%. The patients' mean GCS, RTS, ISS, NISS, and TRISS
      scores were 13.41 +/- 0.31, 10.65 +/- 0.26, 17.04 +/-1.20, 21.94 +/- 1.45, and
      9.52 +/- 2.37, respectively. The patients were divided into two groups as ISS =
      NISS (53.3%) and ISS < NISS (46.7%). CONCLUSION: ISS and NISS both performed well
      in mortality prediction of firearm injuries. NISS demonstrated no superiority to
      ISS for prediction of mortality in these patients.

PMID- 20037874
TI  - Outcome of olecranon osteotomy in the trans-olecranon approach of intra-articular
      fractures of the distal humerus.
AB  - BACKGROUND: The trans-olecranon approach has been suggested to improve the
      visualization of complex intra-articular distal humerus fractures. Significant
      osteotomy complications have prompted a search for alternative approaches. The
      purpose of this series was to study the outcome of the olecranon osteotomy in
      terms of union and complications and the ultimate outcome of the fracture.
      METHODS: Ninety-four patients with intra-articular fractures of the distal
      humerus (type C3) were treated by open reduction and internal fixation using the
      trans-olecranon approach. The patients were followed from 6 to 48 months, with an
      average follow-up of 24 months. RESULTS: All osteotomies united in an average of
      11 weeks (range, 8-20 weeks). There was no non-union, although union was delayed
      in four osteotomies, which all healed by 20 weeks without any intervention. The
      most frequent complication in this study was symptomatic osteotomy fixation in
      19% of patients, all of whom underwent a secondary procedure for the removal of
      the implant after the osteotomy had united. Seventy-one percent of the
      unsatisfactory results were seen in those patients who had symptomatic olecranon
      fixation. CONCLUSION: Despite a few manageable complications, the trans-olecranon
      approach is essential for the adequate visualization and fixation of the complex
      fracture of the distal humerus. Adequate fixation of the osteotomy is essential
      to prevent complications and achieve a satisfactory outcome.

PMID- 20037875
TI  - [Outcomes of surgical therapy and prognostic factors in spontaneous gastric tumor
      perforation].
AB  - BACKGROUND: The aim of the present study was to evaluate the clinicopathological
      features in patients with perforated gastric cancer, to point out the surgical
      approaches, and to analyze the factors that affect morbidity and mortality.
      METHODS: The data of 24 patients with perforated gastric cancer who underwent
      emergency intervention between 1996 and 2006 were retrospectively analyzed. The
      overall age was 60.6 years, and 62.5% of the patients were male. RESULTS: The
      tumor was localized at the antrum most frequently (66.7%), and stage IV disease
      was present in 66.7% of the patients (n = 16). Concomitant disease was present in
      58.3% of the patients (n = 14). In 54.2% of patients (n = 13) primary repair and
      omentopexy, in 20.8% (n = 5) D0 or D1 total gastrectomy, in 8.3% (n = 2) D0
      subtotal gastrectomy, in 8.3% (n = 2) D0 wedge resection, and in 8.3% (n = 2)
      staged D2 total gastrectomy were performed. The morbidity rate was 29.2% (n = 7)
      and the mortality rate was 25% (n = 6). Multivariant analysis showed that diffuse
      peritonitis and the period between perforation and operation (longer than 24
      hours) were effective on prognosis, either on morbidity (p = 0.002 and p = 0.002,
      respectively) or on mortality (p = 0.009 and p = 0.000, respectively).
      CONCLUSION: Postoperative morbidity and mortality rates are high in patients with
      perforated gastric cancer. In resectable cases, one-stage radical gastrectomy
      should be encouraged if conditions allow. In patients with diffuse peritonitis
      and poor general condition, palliative surgery or staged radical gastrectomy
      should be considered. High rates of mortality and morbidity can be reduced with
      early diagnosis and with the surgical control of gastric perforation before
      peritonitis.

PMID- 20037876
TI  - [Unusual causes of intestinal perforation and their surgical treatment].
AB  - BACKGROUND: Intestinal perforation is one of the major causes of obligatory
      surgical intervention. There can be many different causes of perforation. The aim
      of this study was to evaluate the unusual causes and the surgical treatment.
      METHODS: In our clinic, we operated 675 patients due to intestinal perforation
      over a period of six years. Perforation due to brid, trauma, colorectal tumor,
      mesenteric ischemia, hernias, and iatrogenic injuries were considered as usual
      causes and excluded from the study. The remaining 37 patients (22 male, 15
      female; mean age 53.2; range 25 to 80 years) were analyzed. For statistical
      analysis, Mann-Whitney U and chi-square tests were used, and p < 0.05 was
      considered significant. RESULTS: A localized or generalized peritonitis was the
      most common symptom. Leukocytosis was found in 18 patients and free abdominal air
      was seen in 20 patients; bedside ultrasonographic examination was done in 17
      patients. The most prevalent etiological factors were non-Hodgkin lymphoma, Crohn
      disease and internal herniation, respectively. Eight patients died; their time to
      laparotomy was significantly longer (8.7 days), and half of them had malignant
      small bowel tumor in perforation etiology. CONCLUSION: Mortality and morbidity
      rates are high in intestinal perforations due to unusual causes. Delayed
      laparotomy and malignant etiology may be the main factors.

PMID- 20037877
TI  - [A motivating experience for emergency medical services: the first Turkish
      Ambulance Rally].
AB  - BACKGROUND: The aim of this study was to evaluate the first "Turkish Ambulance
      Rally", which provides training and motivation for the rally teams and introduces
      the prehospital emergency medical services of Turkey via international
      participation. METHODS: Data in this descriptive study were collected using
      quantitative and qualitative research methods. Quantitative data were summarized
      in distribution and averages, whereas qualitative data were summarized in shared
      views and comments. There were totally 10 teams, with 96 participants; only two
      competitors were female. RESULTS: Mean scores of driving techniques, locating
      address /patient transferral, advanced life support, and patient-carrying
      techniques were 93.1, 74.8, 70.4, and 67.6, respectively. The question regarding
      the organization's effect on the teams in the deployed city and expansion of
      motivation to the city was scored lowest (2.5%), while desire for re-competition
      was scored highest (95.8%) in feedback results. According to the qualitative
      data, it was determined that the scientific content of the stage scenario was
      adequate, evaluations were made objectively, and participants and officials
      obtained professional benefits. However, it was also determined that these
      benefits did not project to all emergency medical services. CONCLUSION: The rally
      was both beneficial and motivational for participants. It is considered that the
      more extensive contribution of the rally is the increased motivation of the
      workers and of the consciousness of the community.

PMID- 20037878
TI  - [The reconstruction of soft tissue defects in the elbow area: a treatment
      algorithm proposal].
AB  - BACKGROUND: The reconstruction of soft tissue defects of the elbow area
      (including antecubital fossa and peri-olecranon area) should be performed with
      the most appropriate soft tissue and functional rehabilitation immediately.
      METHODS: Ten patients were included in this study. One had a brachial artery
      defect, another had postburn axillary contracture deformity, and a third had an
      ulnar bone body fracture in addition to their soft tissue defects, while the
      remaining seven had only soft tissue defect. Patients underwent surgical closure
      either by local arm fasciocutaneous flap (1), radial forearm flap (1), multiple Z
      plasty (1), pedicled latissimus dorsi muscle flap (3), or with the antecubital
      fasciocutaneous island flap (4). RESULTS: The follow-up was 9 months to 4 years
      (mean: 19 months). All the flaps achieved wound closure without losing the range
      of motion at the elbow joint. CONCLUSION: Surgical closure of the antecubital
      fossa and peri-olecranon areas can be a challenge for plastic surgeons since this
      area includes numerous neuro-vascular bundles and a functional joint. Therefore,
      we describe herein an algorithm for the treatment of defects in these areas from
      the inspiration in our clinical experience and a literature review. Our algorithm
      will help to decide the most appropriate choice among all of the surgical options
      available.

PMID- 20037879
TI  - [Mortality factors in flame and scalds burns: our experience in 816 patients].
AB  - BACKGROUND: Our aim was to evaluate the effective factors on mortality in flame
      and scald burns in the Diyarbakir region. METHODS: The data of 816 patients who
      applied to the Dicle University Emergency Department between January 2001 and May
      2005 with flame and scald burns were investigated retrospectively. The patients
      were separated into two groups as alive or deceased. Gender, age, burns shapes,
      burn degrees and rates, burn regions, admission periods, hospitalization times,
      complications, and the treatments were analyzed. RESULTS: 43.5% of the patients
      were female and 57.5% were male. Six hundred fifty-eight patients were under 6
      years old. 70.5% of burns occurred as a result of negligence; 76.5% occurred due
      to scald and 23.5% due to flame. In cases of death, 39 patients were under 10
      years old. The mean age was 9.32 years. The average hospitalization period was
      10.37 days. The most common complication was wound infection. The mortality rate
      was 6.1%. CONCLUSION: The mortality rate was higher among patients who were
      hospitalized longer than 15 days (p = 0.030); whose burns were due to suicide
      attempt (p = 0.002); who used shoe paint on the burn wounds instead of treatment
      (p = 0.000); who had more than 40% second-degree burns (p = 0.000) or more than
      20% third-degree burns (p = 0.000); and among those with acute respiratory
      failure, compartment syndrome, hypoalbuminemia, and sepsis (p = 0.000).

PMID- 20037880
TI  - The effects of habitual negligence among families with respect to pediatric
      burns.
AB  - BACKGROUND: In this study, scald burns in a Turkish population (0-16 years of
      age) were studied with reference to their occurrence and common causes. METHODS:
      Of the burn victims hospitalized at the Burns Unit of Ankara Numune Education and
      Research Hospital between April 2001 and December 2003, 354 patients were aged 3
      months to 16 years and 228 (64.4%) were male. RESULTS: When burn causes were
      examined, scald burns were the primary type, reported in 77.7% (275) of the
      patients (p < 0.001). Scalds were the most frequent burn agents in the pediatric
      population. Tea is a traditional beverage in Turkey. It is consumed especially at
      breakfast and throughout the day until late at night. Tea in Turkey is steeped
      and brewed for consumption. As brewing and steeping is a time-consuming process
      and the tea is served hot, the appropriate level of care regarding the hot tea is
      neglected. Consequently, tea carries a serious potential to cause burns in this
      country. Of the scalded children, 93 scald burns (33.8%) were due to the tea
      itself or to the boiling water used in steeping tea, and 87.1% of these children
      were preschoolers. The mortality rate was 7.1% in the hospitalized children
      group. CONCLUSION: Traditional behaviors may sometimes have some serious
      unexpected consequences. In households where family members tend to ignore an
      ongoing problem, governmental and non-governmental organizations should consider
      taking preventive measures to protect the children from the devastating
      consequences of such negligence.

PMID- 20037881
TI  - Acute abdomen due to rupture of hemangiopericytoma of the greater omentum: case
      report.
AB  - Hemangiopericytoma (HP) is a vascular tumor that mostly develops in soft tissues.
      The greater omentum is a very rare site for its occurrence. We present herein the
      clinical evaluation and outcome of a very rare case of HP that caused acute
      abdomen. We evaluated a case of acute abdomen due to rupture of a HP of the
      greater omentum. The clinical and laboratory findings and treatment modality are
      reported. A 70-year-old patient with severe abdominal pain was operated with the
      diagnosis of acute abdomen. A semi-solid mass (12 x 10 x 6 cm) originating from
      the greater omentum was detected during surgery. There was active bleeding from
      the tumor. Pathologic evaluation of this lesion was reported as benign HP. HP of
      the greater omentum can be the cause of intraabdominal bleeding leading to acute
      abdomen. Surgical resection is the treatment of choice, especially in benign
      hemangiopericytomas.

PMID- 20037882
TI  - Pneumocephalus following gunshot injury to the thoracic vertebral column: a case
      report.
AB  - Subarachnoid pleural fistula (SPF) following injury to the vertebral column is an
      extremely rare complication and is usually described after blunt trauma. We
      report the first case of SPF with pneumocephalus due to a gunshot wound to the
      spine.

PMID- 20037883
TI  - Delayed diaphragmatic hernia: an unusual complication of tube thoracostomy.
AB  - The nature of a tube thoracostomy -a blind maneuver- renders it subject to
      complications. Nevertheless, it is very uncommon to create a diaphragmatic hernia
      with this procedure. Herein, we present the occurrence of this complication after
      six months under emergency conditions that was treated by thoracotomy.

PMID- 20037884
TI  - Popliteal artery embolism by Ascaris lumbricoides: a case report.
AB  - Arterial occlusive diseases are highly prevalent and constitute the leading
      overall cause of death. Adverse events are due to the effects of impaired
      circulation on critical end organs, namely the brain, heart, abdominal viscera or
      extremities. Acute thromboembolism remains a major surgical challenge. Even with
      optimal surgical management, acute lower extremity ischemia resulting from
      thromboembolic ds continues to cause significant morbidity and mortality. We
      report a case of thromboembolism of the left popliteal artery by an Ascaris worm
      in a patient with oriental cholangiohepatitis.

PMID- 20037885
TI  - Traumatic aortic injury: a case report.
AB  - Trauma is the leading cause of death under the age of 35 years worldwide.
      Traumatic aortic rupture is responsible for 18% of all road accident mortality.
      Eighty percent of these patients die at the scene of the accident. Of the
      survivors, 50% die within 24 hours if left untreated. Rapid transport and
      resuscitation, awareness of the injury, availability of multi-slice computed
      tomography (MSCT), and timely intervention can significantly improve survival in
      aortic injury.

PMID- 20037886
TI  - Attempted suicide with screw penetration into the cranium.
AB  - Intracranial foreign bodies are usually secondary to penetrating injuries. Nails,
      knives, screwdrivers, sewing needles, bullets, and shrapnel have been described
      related to penetrating brain injury. In this report, we present a 34-year-old
      prisoner with an intracranial screw located in the right parietal lobe. The screw
      was used by prisoner in an attempted suicide. A right parietal craniectomy was
      performed, and the screw was removed successfully. It is important to know the
      type of penetrating brain injury preoperatively in order to determine the best
      surgical approach to remove the foreign body settled in the brain. A long-term
      radiological assessment should be performed to detect any future complications,
      such as a cerebral abscess.

PMID- 20037887
TI  - It's the end of the world as we know it* - an era comes to a close.

PMID- 20037888
TI  - Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases:
      hydrogels for protein delivery and cell-based drug delivery as therapeutic
      strategies.
AB  - This review presents two intriguing multidisciplinary strategies that might make
      the difference in the treatment of neurodegenerative disorders such as
      Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the
      controlled delivery of recombinant proteins known to play a key role in these
      neurodegenerative disorders that are released in situ by optimized polymer-based
      systems. The second strategy is the use of engineered cells, encapsulated and
      delivered in situ by suitable polymer-based systems, that act as drug reservoirs
      and allow the delivery of selected molecules to be used in the treatment of
      Alzheimer's and Parkinson's diseases. In both these scenarios, the design and
      development of optimized polymer-based drug delivery and cell housing systems for
      central nervous system applications represent a key requirement. Materials
      science provides suitable hydrogel-based tools to be optimized together with
      suitably designed recombinant proteins or drug delivering-cells that, once in
      situ, can provide an effective treatment for these neurodegenerative disorders.
      In this scenario, only interdisciplinary research that fully integrates biology,
      biochemistry, medicine and materials science can provide a springboard for the
      development of suitable therapeutic tools, not only for the treatment of
      Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of
      severe neurodegenerative disorders.

PMID- 20037889
TI  - Dialysis access: an increasingly important clinical issue.
AB  - Dialysis access, including vascular access for hemodialysis and peritoneal access
      for peritoneal dialysis, is critical in the clinical care of patients with end
      stage renal disease. It is associated with increases in morbidity, mortality, and
      health care costs. A number of problematic issues are involved, some of which are
      addressed in this paper with reference to the most recent publications,
      including: the inappropriately low prevalence of peritoneal dialysis in Western
      countries, which is relevant to access placement in the pre-dialysis stage; the
      excessively high use of central venous catheters in incident and prevalent
      dialysis patients; the diagnosis and treatment of steal syndrome; the advantages
      and limitations of antiplatelet therapy; and finally, the correct pre-operative
      evaluation and subsequent surveillance of the vascular access.

PMID- 20037890
TI  - Quantifying recirculation in extracorporeal membrane oxygenation: a new technique
      validated.
AB  - RATIONALE: The efficacy of veno-venous extracorporeal membrane oxygenation is
      limited by the phenomenon of recirculation, which is difficult to quantify.
      Existing measurement techniques using readily available equipment are
      unsatisfactory. OBJECTIVES: 1) To compare the accuracy of measurements of
      recirculation made using equations comparing blood oxygen content or saturation
      alone at different points in an ex vivo circuit; 2) to validate a new step-change
      technique for quantifying recirculation in vivo. METHODS: anesthetized greyhound
      dogs cannulated for veno-arterial support were connected to a circuit that
      allowed the creation of a known level of recirculation ex vivo and blood oxygen
      content/saturation monitoring. In two dogs, the accuracy of measurements derived
      from oxygen content and oxygen saturation were compared. The potential of a new
      technique for measuring recirculation in vivo by comparing the oxygen content of
      blood sampled during oxygenator bypass to that following a step-change in circuit
      oxygenation was demonstrated in a veno-venous pilot study and validated in a
      three-dog veno-arterial study. RESULTS: Measurements made using oxygen content
      versus oxygen saturation showed superior correlation with true recirculation
      (r(2)=0.87 vs. 0.64, p<0.0001) and less proportional measurement bias (10.3% vs.
      49.8%, p=0.0045). Measurements of recirculation made using a step-change in
      circuit oxygenation and comparing oxygen content as is required for measuring in
      vivo recirculation overestimated by only 18.6% (95% Cl: 3.9-33.2%) and had
      excellent correlation with true values (r(2)=0.89). CONCLUSIONS: 1) Measurement
      of recirculation using oxygen content is superior to that using oxygen saturation
      alone, which demonstrates significant measurement bias; 2) the novel step-change
      technique is a sufficiently accurate technique for the measurement of
      recirculation in animal models.

PMID- 20037891
TI  - Evolution of hemodialysis access resistance: a longitudinal 5-year model using
      functional principal components analysis.
AB  - PURPOSE: Arteriovenous fistulae (AVF) and grafts (AVG) are the preferred accesses
      in hemodialysis (HD). By monitoring access resistance (AR) one can potentially
      identify problems with an established HD access, but little is known about how
      these changes in AR occur, or the variations between the two access types as they
      mature longitudinally. We postulated that AR evolves differentially between AVF
      and AVG, a critical aspect to further understanding of the natural history of HD
      accesses. To describe these changes, we applied a novel statistical methodology
      of functional principal component (FPC) analysis. METHODS: Using ultrasound
      dilution flow studies, we retrospectively studied 479 functional HD accesses in
      which a total of 4573 assessments were made. Accounting for patient factors of
      age, race, gender and diabetes mellitus (DM) status, we employed a multivariate,
      mixed-effects model. Using the mean effects of those covariates, we then applied
      FPC analyses to assess the longitudinal, timedependent changes between AVFs and
      AVGs over a 5-year period. RESULTS: Both types of upper-arm access were
      associated with a lower initial AR. Older age and DM were associated with a
      higher AR. Longitudinal AR varied significantly for both AVF and AVG, between the
      upper arm and lower arm. As a function of time, AVG was associated with an
      increasing AR. Conversely, AVF, especially upper-arm ones, demonstrated a
      longitudinal drop in AR. CONCLUSIONS: Evolutionally, AR can be predicted not only
      by the type of access, but also by the location along the arm of that access and
      by clinical patient factors. Longitudinal change in AR does differ between AVG
      and AVF. Our report provides the foundation of observed changes over time and
      provides insight as to how these variations are affected. We endorse ongoing
      surveillance to screen for clinical sequelae, even years from initial placement.

PMID- 20037892
TI  - Inflammation and oxidative stress in end-stage renal disease patients treated
      with hemodialysis or peritoneal dialysis.
AB  - PURPOSE: The impact of different dialysis modalities on oxidative stress and
      inflammation and the factors implicated in this interrelationship have not been
      adequately studied. This study was designed to comparatively evaluate the effect
      of hemodialysis (HD) and peritoneal dialysis (PD) on oxidative stress and
      inflammatory biomarkers and to search for associated factors. METHODS: We studied
      20 HD, 11 PD patients and 11 healthy controls. Calculations were based on total
      antioxidant capacity (TAC) and superoxide dismutase (SOD), by spectrophotometry,
      as oxidative stress biomarkers; and high sensitivity CRP (hs-CRP), Interleukin-6
      (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha), by ELISA, as inflammation
      biomarkers. RESULTS: HD and PD patients showed significantly increased levels of
      TA C, SOD and hs-CRP compared to healthy controls. No significant difference was
      observed in TNF-alpha and IL-6. Compared to HD patients, PD patients showed TNF
      alpha levels that were increased, although non-significantly, and significantly
      higher homocysteine (Hcy). No differences were observed for IL-6, hs-CRP, TA C
      and SOD. In HD patients, significant positive correlations were found between
      intact parathyroid hormone (iPTH) and TNF-alpha, and between uric acid (UA) and
      TAC. Beta2-microglobulin (Beta2M) was negatively correlated with TAC, total
      cholesterol (TC) positively with TNF-alpha and negatively with SOD, and
      triglycerides (TG) correlated positively with TNF-alpha. In PD patients, TG
      correlated positively with TNF-alpha, HDL-cholesterol negatively with TNF-alpha,
      LDL-cholesterol negatively with SOD, and Beta2M negatively with SOD. CONCLUSIONS:
      HD and PD patients show similar degrees of inflammation and oxidative stress
      activation. Factors such as UA, iPTH, Beta2M and lipid profile correlate to
      oxidative stress and inflammatory biomarkers in both HD and PD patients.

PMID- 20037893
TI  - Two cases of silent superior vena cava syndrome associated with vascular access
      and end-stage renal disease.
AB  - Due to the unavoidable use of indwelling devices and the magnitude of the
      operative problems encountered, superior vena cava syndrome (SVCS) has become a
      serious threat for patients with a history of multiple catheter placements. True
      diagnosis sometimes is not available due to paucity of symptoms or due to the
      inadequate considerations of the disease. Particularly in patients with chronic
      kidney disease, the evidence of central venous occlusion dictates the avoidance
      of placing peripheral dialysis access in this extremity. In this article, we
      report two patients (case 1- a patient with end stage renal disease and case 2 -
      a patient with chronic kidney disease) with silent SVCS related to stenosis
      resulting from indwelling pacemaker leads. Furthermore, the first patient had an
      extrinsic factor of compression, a brachial artery pseudoaneurysm - which
      although it was not causative - it may certainly have contributed to the
      development of SVCS. The brachial artery pseudoaneurysm restricted even more the
      flow to cephalic vein and consequently to superior vena cava. Though pacemaker
      leads have been well identified previously in the literature as a cause of the
      SVCS, the brachial artery pseudoaneurysm causing extrinsic compression
      constitutes a novel factor. Through the publication of this paper the awareness
      of SVCS in these patients shall be definitely enhanced. Moreover, physicians,
      nurses and patients shall be educated regarding the requirement for peripheral
      vein presentation in chronic kidney disease.

PMID- 20037894
TI  - Visual neuropraxia and progressive vision loss from thyroid-associated stretch
      optic neuropathy.
AB  - PURPOSE: Animal models have provided information on the tensile strength of the
      optic nerve, but to our knowledge no in vivo study of the tensile strength of the
      human optic nerve has been reported. Accordingly, we present 3 cases of stretch
      optic neuropathy, an often unrecognized cause of vision loss from thyroid eye
      disease. METHODS: Observational study of thyroid-associated stretch optic
      neuropathy. RESULTS: Three cases of stretch optic neuropathy were identified.
      Visual acuity was better than 20/40. Two patients had arcuate scotoma. Moderate
      to severe proptosis of 25 to 33 mm was present, without evidence of apical
      orbital compression. Two patients had retinal hemorrhages suggesting venous
      stasis retinopathy; the venous stasis retinopathy resolved after orbital
      decompression. Orbital decompression resulted in improvement of visual function.
      The rate of decibel sensitivity loss on automated perimetry was estimated at 
      0.042 dB/da in one case, with complete blindness projected to occur within 785
      days from the onset of visual symptoms. CONCLUSIONS: Stretch optic neuropathy
      presents initially as neuropraxia with temporary visual loss. Orbital
      decompression should be considered for treatment before permanent and
      irreversible visual loss ensues.

PMID- 20037895
TI  - Assessment of anterior chamber angle using Visante OCT, slit-lamp OCT, and
      Pentacam.
AB  - PURPOSE: To assess and compare the anterior chamber angle (ACA) by different
      anterior segment imaging techniques. METHODS: Forty healthy eyes of 40 normal
      subjects were recruited and 3 consecutive measurements of ACA were determined
      prospectively utilizing Visante optical coherence tomography (OCT), slit-lamp OCT
      (SL-OCT), and Pentacam. Statistical significance of interdevice differences
      between measurements was evaluated by Wilcoxon signed rank test and Bland-Altman
      analysis. The repeatability of 3 consecutive measurements was analyzed by
      repeated measured analysis of variance. RESULTS: Mean nasal and temporal ACA were
      detected as 31.2+/-8.7 and 32.1+/-8.5 degrees by Visante OCT; 41.6+/-5.9 and
      41.8+/-5.2 degrees by Pentacam; and 42.9+/-10.0 and 43.3+/-10.1 degrees by SL
      OCT. All devices displayed a high intrasession repeatability (Scheffe multiple
      comparison, p>0.05). ACA detected by Visante OCT were found significantly
      different from ACA calculated by Pentacam and SL-OCT (p<0.05). On the other hand,
      ACA data obtained by Pentacam and SL-OCT were found to be statistically similar
      (p>0.05). CONCLUSIONS: Although noncontact ACA measurements using all modalities
      were easy to handle and demonstrated good repeatability in healthy participants,
      the tested devices were not regarded as comparable. Hence, the clinician should
      take the different modalities into consideration during ACA assessment using
      various devices.

PMID- 20037896
TI  - Two cases of corneal perforation after oral administration of nonsteroidal anti
      inflammatory drugs: oral NSAID-induced corneal damage.
AB  - PURPOSE: To report 2 cases of corneal perforation associated with the use of oral
      nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: In a 62-year-old woman
      and a 79-year-old woman, corneal perforation occurred after 7 days and 5 months
      of oral NSAIDs administration, respectively. RESULTS: After NSAIDs were
      discontinued, the cornea epithelialized and the anterior chamber formed within 14
      and 10 days, respectively. CONCLUSIONS: It is well known that topical NSAIDs
      cause corneal perforation. Observations in the present cases suggest that the
      oral administration of NSAIDs may also cause corneal damage, and hence, medical
      professionals should consider the risk of damage to the cornea when administering
      these drugs orally.

PMID- 20037897
TI  - Clinical evaluation of the Canon TX-10 noncontact tonometer in healthy eyes.
AB  - PURPOSE: To assess the accuracy and repeatability of intraocular pressure (IOP)
      measurements obtained with the Canon TX-10 noncontact tonometer (NCT), using the
      Goldmann applanation tonometer (GAT) as the gold standard. METHODS: Seventy-three
      young healthy subjects were enrolled in the study. Central corneal thickness
      (CCT) was obtained with Orbscan Topography System and then repeated IOP
      measurements were obtained with both tonometers. Canon TX-10 NCT was performed
      first, followed by GAT. Another study sample of 32 young healthy subjects was
      used to test the repeatability with both tonometers. Two sets of data were
      acquired separated by 1 week. Plotting the difference between the methods against
      the mean was done to compare the tonometers and the intersession variability. The
      hypothesis of zero bias was examined by a paired t test. The 95% limits of
      agreement (LoA) were also calculated. RESULTS: No statistically significant
      differences were found when comparing the Canon TX-10 NCT with GAT, displaying
      close level of agreement with GAT as seen by the 95% LoA (-4.78 mmHg to +4.00
      mmHg). CCT ranged from 419 microm to 585 microm and no relationship was found
      between CCT and IOP measurements. The coefficients of repeatability were 3.70
      mmHg and 3.41 mmHg for GAT and TX-10 tonometers, respectively. CONCLUSIONS: There
      was a good agreement between Canon TX-10 and GAT in healthy subjects. From the
      results obtained here, CCT appears to not affect IOP measurements when CCT is
      thinner than 570 microm.

PMID- 20037898
TI  - Retinal mass in a case of pediatric myelodysplastic syndrome (refractory anemia
      with excess of blasts).
AB  - PURPOSE: Myelodysplastic syndrome is a rare childhood clonal hematologic disorder
      characterized by dysplastic hematopoiesis and progression to leukemia. METHODS:
      Case report. RESULTS: An 8-year-old boy with low-grade fever, easy fatigability,
      and pallor of 3 months duration showed pancytopenia with 9% circulating blast
      cells. The bone marrow aspirate revealed striking trilineage dysplasia with 13%
      of blast cells. Cytogenetic analysis revealed 46, XY, del (20) (q11;q13). The
      findings were diagnostic of myelodysplastic syndrome with refractory anemia with
      excess of blasts in accordance with the World Health Organization criteria
      modified for pediatric age group. Fundus examination revealed a sickle-shaped
      hanging retinal mass of right eye. Biopsy/aspiration cytology of the retinal mass
      was not done in this case owing to risk of severe bleeding, a common feature in
      any hematologic malignancy. The child had been included in pediatric acute
      myeloid leukemia trials as the parents were not ready for stem cell
      transplantation, but he died after 3 months due to overwhelming infection.
      CONCLUSIONS: Myelodysplastic syndrome of childhood may present with retinal mass
      along with other hematologic features. Biopsy/aspiration cytology of the mass
      should not be attempted as it may cause intraocular hemorrhage.

PMID- 20037899
TI  - Use of amniotic membrane transplantation in isolated conjunctival Bowen disease:
      a case report.
AB  - PURPOSE: To report a case of isolated conjunctival Bowen disease treated with
      surgical resection and amniotic membrane transplantation. METHODS: Interventional
      case report. RESULTS: A 70-year-old man was admitted to our clinic with a large
      conjunctival verrucous plaque well-demarcated in the correspondence of the bulbar
      conjunctiva in the superior quadrant of the left eye with involved limbal and
      corneal surface. Ophthalmologic examination on slit-lamp examination and color
      fundus photographs were carried out before surgery and the results were
      evaluated. CONCLUSIONS: Treatment options and treatment studies of Bowen disease
      are difficult because there are a variety of different protocols and the success
      of the management depends on several factors (body site, lesion size, number of
      lesions, and thickness). In the conjunctival localization of the lesion, amniotic
      membrane transplantation appears to be a useful therapeutic choice after surgical
      resection of the lesion used to reconstruct ocular and conjunctival surface.

PMID- 20037900
TI  - Repeated surgery for acute acquired esotropia: is it worth the effort?
AB  - PURPOSE: Good binocular potential has been a fundamental defining characteristic
      of acute acquired concomitant esotropia (AACE) type II. The purpose of this study
      was to ascertain the clinical features and surgical outcome in children with AACE
      type II who underwent repeated surgery for the sake of binocularity. METHODS: In
      4 children with AACE type II, repeated surgery was performed between 1995 and
      2008. These cases are presented with special attention to their long-term follow
      up and their binocularity outcome. RESULTS: The final binocularity outcome was
      high-grade stereopsis (Lang I/II positive) in all 4 cases. The duration from
      onset of esotropia to the time of regained stereovision was between 20 and 62
      months. In one case, high-grade stereoacuity was only achieved after a second
      surgery. CONCLUSIONS: Our findings support the good binocular potential in
      patients with AACE type II. Despite a complicated course and long-lasting absence
      of stereovision, all patients eventually regained highgrade stereopsis.
      Resolutely aiming at realignment seems to be worth the effort.

PMID- 20037901
TI  - Anterior chamber measurements taken with Pentacam: an objective tool in laser
      iridotomy.
AB  - PURPOSE: Laser iridotomy is the standard first-line intervention in both acute
      and chronic forms of angle closure because it prevents the recurrence of acute
      attacks and virtually eliminates the risk of an acute attack in the fellow eye.
      Pentacam is a new imaging modality which does not require probe contact or an
      immersion bath. The instrument will allow anterior segment morphology before and
      after laser peripheral iridotomy (LPI) to be quantified. The aim of the study is
      to evaluate the objective difference in changes of anterior chamber morphology
      after LPI with Pentacam. METHODS: Twenty eyes with a high risk of angle closure
      were evaluated with Pentacam rotating Scheimpflug camera before and after LPI. We
      measured anterior chamber volume, anterior chamber depth, and chamber angle
      before and after laser treatment. RESULTS: Statistically significant difference
      before and after LPI was noted in all anterior chamber measurements except
      central anterior chamber depth. CONCLUSIONS: This study confirms previous reports
      of increased anterior chamber volume and angle after LPI and Pentacam is a good
      objective instrument to demonstrate the efficacy of LPI.

PMID- 20037902
TI  - Full-thickness macular hole after intravitreal injection of ranibizumab in a
      patient with retinal pigment epithelium detachment and tear.
AB  - PURPOSE: To report a case of full-thickness macular hole (FTMH) after
      intravitreal injection of ranibizumab in a patient with retinal pigment
      epithelium detachment (PED) and tear. METHODS: A 67-year-old woman with PED and
      retinal pigment epithelium (RPE) tear due to age-related macular degeneration was
      studied by biomicroscopy, fluorescein and indocyanine green angiography, and
      optical coherence tomography and was treated with intravitreal ranibizumab.
      RESULTS: The patient developed a FTMH that was observed 1 month after the
      ranibizumab injection. CONCLUSIONS: Intravitreal ranibizumab may create focal
      sites of tractional forces on the retinal surface while contraction of the
      choroidal neovascular membrane may also place forces on the RPE and outer retina.
      Both actions may have as a result contraction and tearing of the retina leading
      to the formation of a FTMH.

PMID- 20037903
TI  - Screening for ophthalmic disorders and visual impairment in a Nigerian school for
      the deaf.
AB  - PURPOSE: To detect the presence of ophthalmic abnormalities and visual impairment
      in deaf students. METHODS: A cross-sectional survey of all students in the school
      for the deaf was conducted following ethical clearance from the Ministry of
      Health. Age, sex, and previous eye examination was recorded for each student as
      well as visual acuity, penlight eye examination, intraocular pressure, dilated
      funduscopy, and refraction (when applicable). Data were analyzed with SPSS
      version 11 and statistical significance inferred at p<0.05. RESULTS: The 156
      (100%) students at the school for the deaf with age range 6-25 years, mean +/-
      standard deviation of 15.6+/-3.3 years, and modal age of 14 years were studied. A
      total of 110 (70.5%) had no previous eye examination, 2 (1.3%) students were
      blind, 5 (3.2%) were visually impaired, 4 (2.6%) had unilateral visual
      impairment, and 4 (2.6%) had unilateral blindness. Blindness was caused by Usher
      syndrome in 1 (50%) and bilateral pigmented macular scar in 1 (50%) patient.
      Uncorrected refractive errors were the leading cause of unilateral visual
      impairment (75%), visual impairment (60%), and unilateral blindness (50%). Ocular
      abnormality was present in 53 (34%) students while uncorrected refractive error
      (18.6%), retina changes (7%), and allergic conjunctivitis (3.8%) were the leading
      disorders. Previous eye examination was more common among primary school students
      (p<0.0001) and students with ocular abnormalities (p=0.046). CONCLUSIONS:
      Institutions for deaf children should be aware of the high prevalence of
      ophthalmic disorders and the importance of vision to development of a deaf child,
      and conduct an initial and periodic eye examination for every intake.

PMID- 20037904
TI  - Identifying early recurrence of choroidal neovascularization during treatment
      with ranibizumab using C-scan.
AB  - PURPOSE: To demonstrate a new parameter to identify early recurrence of choroidal
      neovascularization (CNV) during treatment with ranibizumab using summated en face
      (C-scan). METHODS: Seventeen patients with CNV secondary to age-related macular
      degeneration were enrolled in this retrospective study. Each patient received
      ranibizumab administered monthly for 3 months and their progress was monitored at
      1 week and then at monthly intervals. RTVue spectral domain optical coherence
      tomography (OCT) was performed in all patients monthly using summated en face (C
      scan) subanalysis and was compared with the standard programs for qualitative
      analysis (Line Scan) and quantitative analysis (macular thickness-MM5 Scan).
      RESULTS: We observed during the control examination an increase of hyporeflective
      area (dark spot) mean early fluid accumulation in the layer corresponding to the
      outer segment of photoreceptors. We did not observe any morphologic
      characteristics of recurrence of CNV in the standard SD OCT examination. At this
      time, no treatment was done. We scheduled a new examination in 30 days. After 30
      days, the patients presented initial signs of CNV recurrence, and ranibizumab
      reinjection was necessary. In all cases, we observed change in the C-scan 30 to
      60 days before the recurrence signs in the standard OCT program. CONCLUSIONS: The
      data suggest that summated en face (C-scan) is useful to identify early
      recurrence of CNV during treatment with ranibizumab. Further studies are required
      to allow for appropriate clinical use of this new technique.

PMID- 20037905
TI  - Sutureless human sclera donor patch graft for Ahmed glaucoma valve.
AB  - PURPOSE: To report the safety and effectiveness of a sutureless human sclera
      donor patch graft covering the subconjunctival portion of glaucoma drainage
      implant tube to prevent its erosion throughout the overlying conjunctiva.
      METHODS: This was a prospective pilot study. Fifteen eyes of 15 consecutive
      patients not responsive to medical and to not-implant surgical glaucoma treatment
      underwent Ahmed glaucoma valve (AGV) implant surgery with sutureless human sclera
      donor patch graft. The surgical procedure included AVG implant placed 8 mm behind
      the corneal limbus and fixed to the sclera with two 9-0 black nylon sutures. The
      tube was passed through the scleral tunnel, parallel to the corneal limbus, and
      shortened at the desired length. The anterior part of the tube was covered with
      human donor scleral graft and kept in place with fibrin glue (Tissue Coll) under
      the conjunctiva. Examinations were scheduled at baseline and then at 1 week and
      1, 3, 6, and 12 months after surgery. RESULTS: At 12-month follow-up, the best
      corrected visual acuity did not significantly improve from baseline 0.78+/-1.2
      logMAR, whereas mean intraocular pressure significantly decreased from
      preoperative values of 29.8 (SD 8.4) mmHg. In all cases, the scleral patch was
      found in place at each check during the follow-up period. No conjunctival erosion
      over the AGV tube nor sign of endophthalmitis was recorded at any time during the
      follow-up period. CONCLUSIONS: AVG implant surgery with sutureless human sclera
      donor patch graft represents an effective and relatively safe surgical procedure
      for complicated glaucomas, avoiding conjunctival erosions over the AGV tube.

PMID- 20037906
TI  - Allergic conjunctivitis: a national cross-sectional study of clinical
      characteristics and quality of life.
AB  - PURPOSE: Ocular allergy is one of the most common ocular problems in clinical
      practice and, although easily identified and frequently a mild to moderate
      condition, it has relevant direct and indirect costs. To characterize clinical
      and demographic aspects of allergic conjunctivitis in Portugal, using a
      structured questionnaire. As a secondary outcome, patient's initial therapeutic
      and health care options, self-perception of health, and work/school absenteeism
      were also evaluated. METHODS: A cross-sectional study, in 16 ophthalmology
      departments of central or regional hospitals, in patients diagnosed with allergic
      conjunctivitis during the spring of 2006. RESULTS: A total of 220 patients were
      enrolled (mean age of 31.4+/-18.5 years). A quarter of these patients had >5
      episodes of ocular allergy in the past year, 59.3% all year-round episodes, and
      most presented associated comorbidities (allergic rhinitis 45.9%, asthma 15.5%).
      They had significant impairment of their overall quality of life during an acute
      episode (45.6% > or =6 in a 10-point severity scale). Only 19.4% had an
      appointment with an ophthalmologist as a first action and most (56.1%) started
      with self treatment measures. Only 37.2% had a previous allergy diagnostic
      evaluation. CONCLUSIONS: In this cross-sectional study of allergic conjunctivitis
      patients seen in ophthalmology departments, we found a significant impairment of
      self-rated health status during an ocular allergy episode. Moreover, most
      patients had year-round episodes and started ocular allergy management with self
      treatment measures.

PMID- 20037907
TI  - Molecular identification of adenoviral conjunctivitis in Turkey.
AB  - PURPOSE: The aim of the study was isolation of adenoviruses by cell culture and
      identification using polymerase chain reaction (PCR) and phylogenetic analyses in
      patients clinically diagnosed with viral conjunctivitis in Ankara, Turkey.
      METHODS: Conjunctival swabs from 34 patients with acute conjunctivitis were
      tested using cell culture isolation and PCR for adenovirus detection. PCR
      positive samples were sequenced and typed. RESULTS: The positive results of
      adenovirus were 26.5% (9 of 34) by the PCR method and 20.6% by culture isolation.
      Nine samples positive at PCR were identified by phylogenetic analyses as human
      adenovirus 8 (HAdV-8) (4 of 9), HAdV-3 (3 of 9), HAdV-4 (1 of 9), and HAdV-B (1
      of 9). CONCLUSIONS: Our study showed types of adenoviruses in patients with
      ocular infection that occurred in this region of Turkey for the first time.
      Furthermore, sequence-based typing method is an efficient, accurate, and rapid
      means of diagnosis and typing of the adenovirus and has significant clinical and
      epidemiologic implications. HAdV-8 was major type for acute conjunctivitis in
      Ankara, Turkey. Further studies are required to reveal the major types of HAdVs
      that cause ocular diseases in this region of the world.

PMID- 20037908
TI  - Vitreous and retinal metastasis from gastric cancer.
AB  - PURPOSE: Intraocular metastasis from gastric cancer is not common and metastatic
      carcinoma to the vitreous or retina is exceedingly rare. We describe a case of
      gastric cancer metastatic to the vitreous and retina. METHODS: Retrospective,
      single-center case report. RESULTS: A 64-year-old woman with advanced gastric
      cancer with multiorgan metastatic disease presented with decreased visual acuity.
      Ophthalmoscopy revealed extensive overlying vitreous seeds and macular
      infiltrations in both eyes. Fine-needle aspiration cytology from the vitreous
      confirmed the diagnosis of metastatic carcinoma. CONCLUSIONS: We report an
      extremely rare case of vitreous and retinal metastasis from gastric cancer.
      Ophthalmologists and oncologists should be aware that gastrointestinal cancer can
      cause intraocular metastasis in the form of vitreous seeds and retinal
      infiltration.

PMID- 20037909
TI  - Reproducibility of OCT/SLO measurements in healthy eyes.
AB  - PURPOSE: To determine the reproducibility of optical coherence
      tomography/scanning laser ophthalmoscope (OCT/SLO) measurements within and
      between observers and within and between sessions in healthy eyes. METHODS: Forty
      eyes of 40 healthy volunteers recruited from the outpatient service of the
      Department of Ophthalmology at the University Hospital of Alexandroupolis,
      Greece, were included. Retinal thickness scans were performed 3 times by two
      experienced operators within each of 3 sessions, which took place within a month,
      using the spectral OCT/SLO. The OCT/SLO provides retinal nerve fiber layer (RNFL)
      thickness and volume measurements and a 3D tomography analysis of optic nerve
      head. Statistical analysis was conducted using Bland-Altman plots, coefficient of
      variation (CoV), and intraclass correlation coefficient (ICC). RESULTS: As shown
      by the CoV values, RNFL parameters were generally found to have high
      reproducibility (CoV ranging from 4.3% to 10.9% for both operators), whereas
      optic disc parameters had scores reaching up to 22.5%. On the other hand, as
      shown by the ICC values, intraobserver and interobserver reproducibility for the
      OCT/SLO was high for optic disc parameters but low for RNFL thickness and volume
      measurements. Interobserver reproducibility was found to be highest for the
      maximum cup depth parameter and lowest for the superior volume. Bland-Altman
      plots indicate that bias is minimal for practically all parameters and
      scatterplot homoscedasticity is high. CONCLUSIONS: According to our data, SLO/OCT
      generally has a good reproducibility profile, as differences between the two
      operators were small. However, additional studies on the reproducibility of
      measurements with the OCT/SLO are needed.

PMID- 20037910
TI  - Recurrent cytomegalovirus corneal endotheliitis after penetrating keratoplasty.
AB  - PURPOSE: To report a case of recurrent cytomegalovirus (CMV) corneal
      endotheliitis after penetrating keratoplasty. METHODS: Penetrating keratoplasty
      (PK) was performed in a 49-year-old man with bullous keratopathy. Pigmented
      keratic precipitates (KPs) were found in the corneal endothelium of the graft 13
      days after surgery, with the subsequent appearance of coin-shaped lesions.
      Confocal microscopy was performed on the corneal endothelium. Aqueous humor was
      analyzed for viral DNA by polymerase chain reaction (PCR). RESULTS: CMV DNA was
      detected from the excised corneal button, and aqueous humor revealed positive
      results for CMV and HSV1 by PCR. Confocal microscopy showed large corneal
      endothelial cells, consistent with the typical owl's eye morphology of CMV
      endotheliitis. After systemic ganciclovir was administered, the pigmented KPs and
      coin-shaped lesions gradually decreased. CONCLUSIONS: Stress from surgery and
      corticosteroid usage can revitalize CMV activity. PCR and confocal microscopy are
      valuable for the diagnosis of CMV corneal endotheliitis.

PMID- 20037911
TI  - Comparison of the clinical presentation and visual outcome in open globe injuries
      in adults and children over 30 months.
AB  - PURPOSE: To compare the clinical presentation and final visual outcome of open
      globe injuries in children and adults in a referral hospital over a 30-month
      period. METHODS: This is an institutional-based prospective study of open globe
      injuries cases presenting in the emergency department between July 2003 and
      December 2005. Patients were divided in 2 groups: group 1, children (2-15 years),
      and group 2, adults (>15 years). All the patients were admitted and emergency
      surgical interventions were undertaken. The clinical features at presentation and
      the final visual acuity are compared. Chi-square and Fisher exact tests were used
      for statistical analysis. RESULTS: Ninety and 84 patients were included in group
      1 and group 2, respectively. The most common places of injuries were home or
      while playing outdoor games in group 1 (67%) and workplace in group 2 (53.5%).
      The presenting features were significantly more grave in group 2. These included
      poor presenting visual acuity (p=0.012), vitreous prolapse (p=0.002), presence of
      relative afferent pupillary defect (p=0.001), and incidence of endophthalmitis
      (p=0.004). Time interval between injury and surgical intervention (p=0.018) was
      better in group 2. Other features, such as presence of hyphema, uveal tissue
      prolapse, cataract, intraocular foreign body, and length or location of
      laceration were similar in both groups. The final visual outcome was similar in
      the groups (p = 0.21), with approximately half of the patients achieving vision
      of 20/60 or better in each group. CONCLUSIONS: The majority of injuries in
      children and adults occurred in their homes or workplaces, respectively. Although
      the clinical presentations of open globe injuries were significantly more grave
      in adults than in children, the final visual outcomes were similar.

PMID- 20037912
TI  - Acute postoperative endophthalmitis caused by Gemella morbillorum.
AB  - PURPOSE: We present a case of Gemella morbillorum endophthalmitis after
      uneventful cataract surgery. METHODS: A 78-year-old woman developed progressive
      blurring of vision, hypopyon, and vitritis in the precocious postoperatory
      following cataract surgery. Pars plana vitrectomy and intraocular lens
      explantation were performed followed by intravitreal injection of vancomycin and
      ceftazidime. Postoperatively, the patient was given hourly topical fortified
      vancomycin according to antimicrobial susceptibility testing. At the final follow
      up visit 6 months after the initial procedure, visual acuity was 20/50 and no
      signs or symptoms of endophthalmitis were observed. RESULTS: The undiluted
      vitreous samples and explanted lens were analyzed. Cultures revealed the growth
      of G morbillorum, an infrequent opportunistic pathogen. CONCLUSIONS: To date,
      this is the second reported case of postoperative endophthalmitis by this
      species. Although endophthalmitis is rare, ophthalmologists should be alert to
      the possibility of patients having endophthalmitis caused by G morbillorum.
      Especially, it is necessary to be cautious with surgery in patients with recent
      infections. A review of the medical literature of this rare ocular infection is
      presented.

PMID- 20037913
TI  - Electrolysis treatment of trichiasis by using ultra-fine needle.
AB  - PURPOSE: To determine the safety and efficacy of electrolysis treatment of
      trichiasis by using ultrafine needle. METHODS: The medical records of 24 lids of
      24 patients who underwent electrolysis treatment for trichiasis by the same
      surgeon (Y.S.) during the period from May 2006 through December 2008 were
      reviewed. The average age of the 24 patients was 59.2 years (range, 43 to 76
      years). Thirteen of the patients were women. RESULTS: The results were considered
      satisfactory if no recurrence of trichiasis occurred for at least 6 months after
      the last electrolysis procedure. Sixteen of the 24 patients (66.6%) had a
      satisfactory result with 1 treatment. Of the 8 patients (33.3%) who had an
      unsatisfactory result, while 5 (20.8%) responded well to 1 additional
      electrolysis, 3 (12.5%) responded well to 2 additional electrolyses to the
      recurrent cilia. The procedure was well tolerated by the patients. All eyelids
      healed within 2 weeks after treatment without any scarring. Faint
      hypopigmentation was visible in 2 patients (8.3%). Mild notching of eyelid
      occurred in 4 patients (16.6%). CONCLUSIONS: Electrolysis treatment by using
      ultrafine (55-microm thickness) needle is an effective and safe method for
      treatment of trichiasis with many advantages over other recognized modalities of
      therapy.

PMID- 20037914
TI  - The combination of diffractive and refractive multifocal intraocular lenses to
      provide full visual function after cataract surgery.
AB  - PURPOSE: To investigate if implantation of a far dominant refractive multifocal
      intraocular lens (IOL) in one eye and a near dominant diffractive multifocal IOL
      in the fellow eye improves range of vision following cataract surgery. METHODS:
      This was a prospective, nonrandomized, case-control study involving 20 patients
      (40 eyes) scheduled for cataract surgery. Inclusion criteria were bilateral
      cataracts, minimum age 50 years, availability for follow-up visits, and informed
      consent. All patients received a far dominant refractive multifocal IOL (ReZoom,
      Abbott Medical Optics) in their dominant eye and a near dominant diffractive
      multifocal IOL (Tecnis ZM900, AMO) in their nondominant eye. Preoperative and
      postoperative measurements (3 months) included refraction, uncorrected visual
      acuity (UCVA), best-corrected visual acuity (BCVA), reading acuity, and reading
      speed. RESULTS: All patients completed the study. We present results of the 3
      month postoperative visit. The patient group comprised 14 females and 6 males,
      with mean age 72 years (SD 6.1 years). Postoperatively, the mean sphere was 0.05
      +/- 0.31 D and the cylinder -0.31 +/- 0.37 D. At the 3-month visit, mean
      binocular distance UCVA was 0.080 logMAR (SD 0.070) and BCVA was 0.030 logMAR (SD
      0.066). The mean binocular near visual acuity was 0.140 logMAR (SD 0.068), mean
      binocular best-corrected, near visual acuity 0.060 logMAR (SD 0.060).
      CONCLUSIONS: The combination of a far dominant refractive multifocal IOL (with
      better distance performance) with a near dominant diffractive multifocal IOL
      (with better near vision) proved to be very suitable to help meet cataract
      patients' visual needs.

PMID- 20037915
TI  - Pneumatic displacement of acute submacular hemorrhage with and without the use of
      tissue plasminogen activator.
AB  - PURPOSE: To evaluate the efficacy of C(3)F(8) gas-assisted pneumatic displacement
      in the treatment of massive submacular hemorrhage, with and without the use of
      tissue plasminogen activator (tPA). METHODS: Twenty-one eyes of 21 patients with
      recently developed (up to 10 days) dense submacular hemorrhage underwent
      intravitreal injection of pure C(3)F(8) gas (0.4-0.5 mL) followed by face-down
      positioning for pneumatic displacement. Seven of them received additional
      intravitreal injection of 25-50 microg tPA. The primary etiology of submacular
      hemorrhage was age-related macular degeneration (n=16), myopic choroidal
      neovascularization (n=2), retinal arterial macroaneurysm (n=2), and trauma (n=1).
      Visual acuity and displacement of hemorrhage were the main outcome measures.
      RESULTS: Follow-up period was 6-12 months. Effective displacement of hemorrhage
      was obtained in 20 of 21 patients within 7 days. Final median Snellen visual
      acuity (0.18) was found significantly improved compared to baseline (0.03)
      (p<0.001). Visual acuity improvement was similar in both groups (p=0.72).
      CONCLUSIONS: Intravitreal injection of C(3)F(8) effectively displaced thick
      submacular hemorrhage and improved visual acuity independently from primary
      cause. Additional tPA use in this study had no impact on the final outcomes.

PMID- 20037916
TI  - Refractive lens exchange with the Acri.Twin asymmetric diffractive bifocal
      intraocular lens system.
AB  - PURPOSE: To evaluate efficacy, safety, and predictability after refractive lens
      exchange (RLE) in patients who had implantation of asymmetric Acri.Twin bifocal
      diffractive intraocular lenses. METHODS: The study comprised 130 eyes of 65
      consecutive patients after RLE who had bilateral implantation of the Acri.Twin
      system. Eyes were divided into myopic and hyperopic groups. Binocular uncorrected
      distance visual acuity, best-corrected distance visual acuity (BCVA), uncorrected
      distance near visual acuity, and best distance-corrected near visual acuity
      (BCNVA) were recorded preoperatively and 6 months after surgery. RESULTS:
      Efficacy indexes were 0.99 for myopic and 0.93 for hyperopic patients at 6 months
      postoperatively. No patients lost >2 lines of BCVA. For the myopic group, 6
      patients gained 1 line, and 10 patients gained >or=2 lines; for the hyperopic
      group, 5 patients gained 1 line, and 6 patients gained >or=2 lines. Safety
      indexes were 1.13 and 1.03 for myopic and hyperopic patients, respectively. No
      patients lost >or=2 lines of BCNVA; for the myopic group, only 2 patients lost 1;
      for the hyperopic group there was no change after surgery. Safety indexes at near
      were 0.99 for myopic and 1.00 for hyperopic patients. Efficacy indexes at near
      were 1.05 for myopic and 1.07 for hyperopic patients. CONCLUSIONS: RLE with
      asymmetric bilateral implantation of the Acri.Twin bifocal IOL is an effective
      procedure for correcting ametropia and presbyopia. Results obtained were safe and
      effective at distance and near for both myopic and hyperopic patients.

PMID- 20037917
TI  - Age differences in the prevalence and co-morbidity of DSM-IV major depressive
      episodes: results from the WHO World Mental Health Survey Initiative.
AB  - BACKGROUND: Although depression appears to decrease in late life, this could be
      due to misattribution of depressive symptoms to physical disorders that increase
      in late life. METHODS: We investigated this issue by studying age differences in
      co-morbidity of DSM-IV major depressive episodes (MDE) with chronic physical
      conditions in the WHO World Mental Health (WMH) surveys, a series of community
      epidemiological surveys of respondents in 10 developed countries (n=52,485) and 8
      developing countries (n=37,265). MDE and other mental disorders were assessed
      with the Composite International Diagnostic Interview (CIDI). Organic exclusion
      rules were not used to avoid inappropriate exclusion of cases with physical co
      morbidity. Physical conditions were assessed with a standard chronic conditions
      checklist. RESULTS: Twelve-month DSM-IV/CIDI MDE was significantly less prevalent
      among respondents ages 65+ than younger respondents in developed but not
      developing countries. Prevalence of co-morbid mental disorders generally either
      decreased or remained stable with age, while co-morbidity of MDE with mental
      disorders generally increased with age. Prevalence of physical conditions, in
      comparison, generally increased with age, while co-morbidity of MDE with physical
      conditions generally decreased with age. Depression treatment was lowest among
      the elderly in developed and developing countries. CONCLUSIONS: The weakening
      associations between MDE and physical conditions with increasing age argue
      against the suggestion that the low estimated prevalence of MDE among the elderly
      is due to increased confounding with physical disorders. Future study is needed
      to investigate processes that might lead to a decreasing impact of physical
      illness on depression among the elderly.

PMID- 20037918
TI  - Culture and the anxiety disorders: recommendations for DSM-V.
AB  - BACKGROUND: The anxiety disorders specified in the fourth edition, text revision,
      of The Diagnostic and Statistical Manual (DSM-IV-TR) are identified universally
      in human societies, and also show substantial cultural particularities in
      prevalence and symptomatology. Possible explanations for the observed
      epidemiological variability include lack of measurement equivalence, true
      differences in prevalence, and limited validity or precision of diagnostic
      criteria. One central question is whether, through inadvertent "over
      specification" of disorders, the post-DSM-III nosology has missed related but
      somewhat different presentations of the same disorder because they do not exactly
      fit specified criteria sets. This review canvases the mental health literature
      for evidence of cross-cultural limitations in DSM-IV-TR anxiety disorder
      criteria. METHODS: Searches were conducted of the mental health literature,
      particularly since 1994, regarding cultural or race/ethnicity-related factors
      that might limit the universal applicability of the diagnostic criteria for six
      anxiety disorders. RESULTS: Possible mismatches between the DSM criteria and the
      local phenomenology of the disorder in specific cultural contexts were found for
      three anxiety disorders in particular. These involve the unexpectedness and 10
      minute crescendo criteria in Panic Disorder; the definition of social anxiety and
      social reference group in Social Anxiety Disorder; and the priority given to
      psychological symptoms of worry in Generalized Anxiety Disorder. Limited evidence
      was found throughout, particularly in terms of neurobiological markers, genetic
      risk factors, treatment response, and other DSM-V validators that could help
      clarify the cross-cultural applicability of criteria. CONCLUSIONS: On the basis
      of the available data, options and preliminary recommendations for DSM-V are put
      forth that should be further evaluated and tested.

PMID- 20037919
TI  - Subtyping social anxiety disorder in developed and developing countries.
AB  - BACKGROUND: Although social anxiety disorder (SAD) is classified in the fourth
      edition of The Diagnostic and Statistical Manual (DSM-IV) into generalized and
      non-generalized subtypes, community surveys in Western countries find no evidence
      of disjunctions in the dose-response relationship between number of social fears
      and outcomes to support this distinction. We aimed to determine whether this
      holds across a broader set of developed and developing countries, and whether
      subtyping according to number of performance versus interactional fears would be
      more useful. METHODS: The World Health Organization's World Mental Health Survey
      Initiative undertook population epidemiological surveys in 11 developing and 9
      developed countries, using the Composite International Diagnostic Interview to
      assess DSM-IV disorders. Fourteen performance and interactional fears were
      assessed. Associations between number of social fears in SAD and numerous
      outcomes (age-of-onset, persistence, severity, comorbidity, treatment) were
      examined. Additional analyses examined associations with number of performance
      fears versus number of interactional fears. RESULTS: Lifetime social fears are
      quite common in both developed (15.9%) and developing (14.3%) countries, but
      lifetime SAD is much more common in the former (6.1%) than latter (2.1%)
      countries. Among those with SAD, persistence, severity, comorbidity, and
      treatment have dose-response relationships with number of social fears, with no
      clear nonlinearity in relationships that would support a distinction between
      generalized and non-generalized SAD. The distinction between performance fears
      and interactional fears is generally not important in predicting these same
      outcomes. CONCLUSION: No evidence is found to support subtyping SAD on the basis
      of either number of social fears or number of performance fears versus number of
      interactional fears.

PMID- 20037921
TI  - NPY moderates the relation between hurricane exposure and generalized anxiety
      disorder in an epidemiologic sample of hurricane-exposed adults.
AB  - BACKGROUND: Neuropeptide Y (NPY) has been found to be anxiolytic in animals and
      humans. A recent study found NPY expression to be inversely correlated with trait
      anxiety. We examined whether rs16147, a functional single nucleotide polymorphism
      in the promoter region of NPY, moderated the relationship between hurricane
      exposure and risk for generalized anxiety disorder (GAD) in an epidemiologic
      sample of adults living in areas affected by the 2004 Florida hurricanes.
      METHODS: Data from this study comes from 616 adults from the 2004 Florida
      Hurricanes study who returned buccal DNA samples via mail. Selection of
      participants occurred via random digit-dial procedures. Participants were
      interviewed via telephone about hurricane exposure and post-hurricane GAD
      symptoms. The outcome measure was DSM-IV GAD diagnosis, assessed via structured
      interview. RESULTS: Rs16147 in NPY was associated with increased risk of GAD
      diagnosis under conditions of high hurricane exposure (P<.01). This gene by
      environment interaction remained significant after adjustment for sex, ancestry
      (as determined by Bayesian clustering of genotypes), and age. CONCLUSIONS: NPY
      rs16147 modifies risk of post-disaster GAD under conditions of high stressor
      (hurricane) exposure. This is the first demonstration of gene-environment
      interaction for this locus.

PMID- 20037922
TI  - Cognitive mediation of clinical improvement after intensive exposure therapy of
      agoraphobia and social phobia.
AB  - BACKGROUND: The present study investigated cognitive mediation of clinical
      improvement in patients with agoraphobia (N=427) or social phobia (N=98)
      receiving high-density exposure therapy in a naturalistic clinical treatment
      setting. METHODS: Patients were assessed before therapy, 6 weeks after the end of
      therapy, and 1 year thereafter, using a self-report assessment battery. Lower
      level mediation analyses provided support for the notion that cognitive changes
      partially mediate clinical improvement after exposure therapy. RESULTS: Changes
      in cognitions relating to physical catastrophes mediated treatment outcome only
      for patients with agoraphobia, whereas changes in cognitions about loss of
      control mediated outcome for both agoraphobia and social phobia patients. Changes
      in relationship satisfaction did not mediate symptomatic improvement.
      CONCLUSIONS: The results extend previous findings by demonstrating mediation in
      an unselected clinical sample and by providing evidence for the specificity of
      mediation effects. They further support the importance of cognitive changes in
      cognitive-behavior therapy.

PMID- 20037924
TI  - Expression of Paracoccidioides brasiliensis CHS3 in a Saccharomyces cerevisiae
      chs3 null mutant demonstrates its functionality as a chitin synthase gene.
AB  - We report the isolation and sequencing of CHS3, a gene that encodes one of
      several chitin synthases in Paracoccidioides brasiliensis, a medically important
      fungus restricted geographically to Latin America. The gene contains a single
      open reading frame of 3817 bp with two introns (71 and 86 bp) and encodes a 1220
      amino acid polypeptide with high similarity to other fungal chitin synthases.
      Northern analysis reveals a high expression of CHS3 in the pathogenic yeast-like
      phase of the fungus and at the end of the mycelium-yeast transition. Expression
      of P. brasiliensis CHS3 in a Saccharomyces cerevisiae chs3 null mutant enhanced
      calcofluor white staining in parallel to an increase in total chitin synthase
      activity and chitin content in its cell wall.

PMID- 20037920
TI  - A preliminary study of the neural mechanisms of frustration in pediatric bipolar
      disorder using magnetoencephalography.
AB  - BACKGROUND: Irritability is prevalent and impairing in pediatric bipolar disorder
      (BD) but has been minimally studied using neuroimaging techniques. We used
      magnetoencephalography (MEG) to study theta band oscillations in the anterior
      cingulate cortex (ACC) during frustration in BD youth. ACC theta power is
      associated with attention to emotional stimuli, and the ACC may mediate responses
      to frustrating stimuli. METHODS: We used the affective Posner task, an attention
      paradigm that uses rigged feedback to induce frustration, to compare 20 medicated
      BD youth (14.9+/-2.0 years; 45% male) and 20 healthy controls (14.7+/-1.7 years;
      45% male). MEG measured neuronal activity after negative and positive feedback;
      we also compared groups on reaction time, response accuracy, and self-reported
      affect. Patients met strict DSM-IV BD criteria and were euthymic. Controls had no
      psychiatric history. RESULTS: BD youth reported more negative affective responses
      than controls. After negative feedback, BD subjects, relative to controls,
      displayed greater theta power in the right ACC and bilateral parietal lobe. After
      positive feedback, BD subjects displayed lower theta power in the left ACC than
      did controls. Correlations between MEG, behavior, and affect were nonsignificant.
      CONCLUSION: In this first MEG study of BD youth, BD youth displayed patterns of
      theta oscillations in the ACC and parietal lobe in response to frustration
      inducing negative feedback that differed from healthy controls. These data
      suggest that BD youth may display heightened processing of negative feedback and
      exaggerated self-monitoring after frustrating emotional stimuli. Future studies
      are needed with unmedicated bipolar youth, and comparison ADHD and anxiety
      groups.

PMID- 20037925
TI  - Water-forming NADH oxidase protects Torulopsis glabrata against hyperosmotic
      stress.
AB  - A heterologous water-forming NADH oxidase was introduced into Torulopsis glabrata
      and the effect on cell growth under hyperosmotic conditions was investigated.
      Expression of the noxE gene from Lactococcus lactis NZ9000 in T. glabrata
      resulted in a marked decrease in the NADH : NAD+ ratio and higher activities of
      key enzymes in water-regenerating pathways, leading to an increase in
      intracellular water content. NaCl-induced reactive oxygen species production was
      also decreased by the introduction of NADH oxidase, resulting in a significant
      increase in the growth of T. glabrata under hyperosmotic stress conditions (3824
      mOsmol/kg). The results indicated that the osmotolerance of cells can be enhanced
      by manipulating water-production pathways.

PMID- 20037927
TI  - [Surgical approach in excision of left atrial myxoma].

PMID- 20037928
TI  - Comparison between the effects of Chuna manipulation therapy and cervical
      traction treatment on pain in patients with herniated cervical disc: a randomized
      clinical pilot trial.

PMID- 20037929
TI  - [Case of small cell carcinoma of the lung with left total pneumonectomy following
      pre-operative chemotherapy + mediastinal lymph node dissection].

PMID- 20037930
TI  - [Imaging diagnosis: Q & A. Lung cancer with adipose tissue (adult Bochdalek
      hernia in adulthood) masquerading pleural effusion].

PMID- 20037931
TI  - [Cities and urbanization in Brazil, 16th-20th centuries].

PMID- 20037933
TI  - Abstracts of the 20th Ljudevit Jurak International Symposium on Comparative
      Pathology. Pathology of the male genital tract. June 5-6 2009, Zagreb, Croatia.

PMID- 20037932
TI  - [Populations, interbreeding, and migrations in the 16th-20th centuries].

PMID- 20037934
TI  - [Visiting the Americas through collections in French museums].

PMID- 20037935
TI  - Educating men how to develop technology: the role of professional housewives in
      the diffusion of electrical domestic appliances in the interwar-period in
      Germany.

PMID- 20037936
TI  - The strange case of Dr. Frankenstein and Mr. Rossum: can dystopian literature be
      considered as a response to technological breakthroughs?

PMID- 20037937
TI  - New technology for social health: the Finsen lamp at the World Exhibition in
      Paris, 1900.

PMID- 20037938
TI  - Women and economic life.

PMID- 20037939
TI  - Economy of Broach during the seventeenth century - gains from the bleaching
      activity.

PMID- 20037940
TI  - Introduction and historical context for the archaeology of institutions of
      reform. part 1: asylums.

PMID- 20037941
TI  - "An irregular and inconvenient pile of buildings": the destitute asylum of
      Adelaide, South Australia and the English workhouse.

PMID- 20037942
TI  - Advances in cardiovascular research: from genes and molecules to clinical
      applications. International symposium. Devin-Bratislava, Slovak Republic, 2008
      September 27-29. Introduction.

PMID- 20037943
TI  - The role of women in the urban economy of Istanbul, 1700-1850.

PMID- 20037944
TI  - Famines in Karnataka 1876-78: some new findings.

PMID- 20037945
TI  - To watch or restrain: female convict prisons in 19th-century Tasmania.

PMID- 20037947
TI  - The traveller's experience of famine Ireland.

PMID- 20037946
TI  - "Women and peace and security": the politics of implementing gender sensitivity
      norms in peacekeeping.

PMID- 20037948
TI  - A few good women: gender stereotypes, the military and peacekeeping.

PMID- 20037949
TI  - Sexual violence in times of war: a new challenge for peace operations?

PMID- 20037950
TI  - Women, peacekeeping and peacemaking: gender balance and mainstreaming.

PMID- 20037951
TI  - Zionism's gender: Hannah Meisel and the founding of the agricultural schools for
      young women.

PMID- 20037952
TI  - [Public morality and counterrevolution: new sociopolitical norms in Guatemala,
      1839-54. Part 2].

PMID- 20037953
TI  - [Images and illustrations of cannibals: Brazilian Indians in 16th-century images
      and texts].

PMID- 20037954
TI  - Portmanteau Jews: Sephardim and race in the early modern Atlantic world.

PMID- 20037955
TI  - [A study of agricultural production, 1927-37].

PMID- 20037956
TI  - [Late Qing social ethics as seen from the case of Yang Yuelou].

PMID- 20037957
TI  - A glimpse into the traditional martial arts in Burma.

PMID- 20037958
TI  - From service to self-service: advice literature as design discourse, 1920-1970.

PMID- 20037959
TI  - Better legs: artificial limbs for British veterans of the First World War.

PMID- 20037960
TI  - A world of unmentionable suffering: women's public conveniences in Victorian
      London.

PMID- 20037961
TI  - Emergent technologies in menstrual paraphernalia in mid-nineteenth-century
      Britain.

PMID- 20037962
TI  - Colour quality and production: testing colour in eighteenth-century France.

PMID- 20037963
TI  - Effect of refrigeration of the antiemetic Cerenia (maropitant) on pain on
      injection.
AB  - Injection pain has been associated with veterinary use of the antiemetic
      maropitant (Cerenia, Pfizer Animal Health). Cerenia is formulated using
      sulphobutylether-beta-cyclodextrin to bind maropitant and mitigate injection
      pain. The objective of this study was to determine whether the temperature of
      Cerenia alters binding between maropitant and sulphobutylether-beta-cyclodextrin
      and affects injection pain. Binding decreased as temperature increased, and
      Cerenia-elicited injection pain increased at warmer drug temperatures. These data
      suggest that the amount of free unbound maropitant increases with temperature and
      that injection pain increases with temperature in a similar fashion. Clinically,
      these studies suggest that injection of refrigerated Cerenia may significantly
      reduce or eliminate pain associated with SC injection of Cerenia.

PMID- 20037964
TI  - Evaluation of the efficacy of a canine influenza virus (H3N8) vaccine in dogs
      following experimental challenge.
AB  - Canine influenza virus (CIV) subtype H3N8 is an emerging pathogen with sustained
      horizontal transmission in the dog population in the United States. This study
      evaluated the efficacy of an inactivated CIV vaccine in 6- to 8-week-old beagle
      pups challenged with virulent CIV. One group of CIV-seronegative pups was
      vaccinated with two doses of a CIV vaccine 3 weeks apart; a second group of pups
      received adjuvanted placebo as a control. Blood samples were collected at various
      times to determine antibody titers. All pups were challenged with a virulent CIV
      isolate 13 days after the second vaccination and monitored for clinical signs of
      respiratory disease, virus shedding, and lung consolidation. Vaccinated pups
      developed hemagglutination inhibition antibody titers after vaccination. The
      severity of clinical signs (P < .001) and the magnitude and duration of virus
      shedding (P < .0001) were significantly lower in vaccinated pups compared with
      control pups. These results demonstrate that the CIV vaccine used in this study
      provides protection against virulent CIV challenge in dogs.

PMID- 20037965
TI  - Effects of top-dress formulations of suxibuzone and phenylbutazone on development
      of gastric ulcers in horses.
AB  - Eighteen mature, healthy horses were divided into three groups (six per group)
      receiving either no treatment, 15 consecutive days of phenylbutazone (PBZ), or 15
      consecutive days of suxibuzone (SBZ) at recommended label doses. Horses underwent
      endoscopy before and after the treatment period and were assigned gastric ulcer
      scores. Gastric ulcer number and severity scores were similar across treatment
      groups. These findings suggest that when administered at the recommended label
      dose for 15 days, neither PBZ nor SBZ causes an increase in the number or
      severity of gastric ulcers over what would be expected with traditional stabling
      and intermittent feeding patterns. Also, PBZ-treated horses did not have more
      severe gastric ulcers than SBZ-treated horses, indicating that SBZ does not
      appear to offer an advantage over PBZ in preventing gastric ulcers when used at
      recommended label doses. However, ulcers in other regions of the gastrointestinal
      tract (e.g., right dorsal colon, duodenum) were not evaluated in horses in this
      study.

PMID- 20037966
TI  - Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain
      AHC7 in dogs with acute idiopathic diarrhea.
AB  - This study evaluated the effect of supplementation with canine-derived probiotic
      Bifidobacterium animalis strain AHC7 (lams Prostora, Procter & Gamble Pet Care)
      on the resolution rate of acute idiopathic diarrhea in dogs randomly assigned to
      receive a placebo (n=18) or the probiotic (n=13). Nutritional management with the
      probiotic fed at 2 x 10(10) CFU/day significantly reduced the time to resolution
      (3.9 +/- 2.3 versus 6.6 +/- 2.7 days; P < .01) and reduced the percentage of dogs
      that were administered metronidazole (38.5% versus 50.0%) compared with placebo.
      Probiotic B. animalis AHC7 may provide veterinarians another tool for management
      of acute diarrhea in dogs.

PMID- 20037968
TI  - [14-year-old patient. What causes tibia vara?].

PMID- 20037967
TI  - Effects of calcium chloride and calcium sulfate in an oral bolus given as a
      supplement to postpartum dairy cows.
AB  - An oral calcium bolus (Bovikalc, Boehringer Ingelheim Vetmedica) supplying
      calcium to dairy cows in the form of calcium chloride and calcium sulfate was
      evaluated to determine the effect on calcium homeostasis immediately after
      calving. Cows in the treatment group received one bolus immediately after calving
      and a second bolus 12 hours later. Control cows received no calcium
      supplementation. Blood was analyzed for ionized calcium, and urine was collected
      for urinary pH determination. Postpartum supplementation with the Bovikalc bolus
      significantly increased serum ionized calcium levels and decreased urine pH
      values.

PMID- 20037969
TI  - [More patients than ever receive artificial hip joints. A profitable business?
      (interview by Dr. med. Thomas Meissner)].

PMID- 20037970
TI  - [Now it is here, the "new influenza". Is your practice prepared?].

PMID- 20037971
TI  - [What form of continuing education for the physician? Professional objectives and
      science].

PMID- 20037972
TI  - [Depression in the man. He doesn't complain but it's killing him (interview by
      Dr. med. Brigitte Moreano)].

PMID- 20037973
TI  - [Pleural punctures brought no improvement. Lung cancer patient with persistent
      dyspnea].

PMID- 20037974
TI  - [Thrombocyte control in bridging. Is it "evidence based" or "expert based"?].

PMID- 20037975
TI  - [Accrue 30 CME points already. The early bird catches the worm].

PMID- 20037976
TI  - [Acute infections of the upper airways].

PMID- 20037977
TI  - [Pre-travel immunizations].

PMID- 20037978
TI  - [Modern management of asthma].

PMID- 20037979
TI  - [Management of stable coronary artery disease].

PMID- 20037980
TI  - [Acute coronary syndrome: prehospital emergency management, therapy at the
      practice physician].

PMID- 20037981
TI  - [Therapy of atrial fibrillation].

PMID- 20037982
TI  - [Therapy of venous thromboembolism].

PMID- 20037983
TI  - [Diagnosis and treatment of osteoarthritis].

PMID- 20037984
TI  - [Ankylosing spondylitis].

PMID- 20037985
TI  - [Elderly need an adapted cancer pain therapy].

PMID- 20037986
TI  - Superiority of the dominant and nondominant hands in static strength and
      controlled force exertion.
AB  - The dominant hand can be defined in such a way that Oldfield's Handedness
      Inventory may not identify the superior hand, i.e., the hand with more strength
      and/or more force control. The dominant and nondominant hands were compared for
      two different grip force-exertion tests. 50 healthy young men (M age = 21.1 yr.)
      performed two tests with each hand: a maximal grip strength test and a controlled
      force-exertion test with dynamic demand. In the latter test, the participants
      matched their submaximal grip force to the changing demand values with real-time
      feedback. The total sum of the differences between the demand value and grip
      force value for 25 sec. was used as an evaluation parameter for the test (unit:
      %). Mean maximal grip force values in the right and left hands were 439.9 N (SD =
      59.1) and 405.6 N (SD = 59.3), respectively. Mean controlled force-exertion test
      values in the right and left hands were 610.3% (SD = 150.2) and 722.6% (SD =
      147.8), respectively. In both tests, the dominant hand was significantly stronger
      and controlled dynamic force better. The relationship between the two hands was
      very high. Based on this study's criteria, the dominant hand was stronger in 34%
      (n = 17) of participants during the maximal grip strength test and more
      controlled in 54% (n = 27) of participants during the controlled force-exertion
      test. Thus, the dynamic force control test showed that for significantly more
      people the dominant hand is stronger and controls force better. Controlled force
      exertion may be a better test for identifying the superior hand.

PMID- 20037987
TI  - Amount of mental practice and performance of a simple motor task.
AB  - The effects of different amounts of mental practice on the performance of a motor
      skill were studied. Research supports the effectiveness of mental practice on
      performance; however, little is known about how much practice is needed and
      whether there is an optimal amount for these practice effects. Participants, 209
      students ages 18 to 44 years (M=20.5, SD=2.9), completed a pre- and posttest of
      dart throwing with the nonpreferred hand. In the practice phase, participants
      completed either 25 (Mental Practice 25), 50 (Mental Practice 50), or 100 (Mental
      Practice 100) trials of the darts task or 50 trials of a catching task (Catching
      Task). Performance for all groups improved from pre- to posttest. Improvements
      for the three mental practice groups were greater than for the Catching Task
      group; however, there were no differences for the three Mental Practice groups.
      The findings support the positive effect of mental practice over a control
      condition and suggest that small amounts of mental practice may be sufficient for
      performance improvements, at least for a simple motor skill.

PMID- 20037988
TI  - The dissociation of small- and large-scale spatial abilities in school-age
      children.
AB  - This experiment with school-age children was designed to assess the extent to
      which training in a "small-scale space"--so-called manual rotation training--can
      improve performance in a "large-scale space." In a preliminary test, 72 9- and 10
      yr.-olds completed a direction estimation test. Half of the children then
      completed manual rotation training or played a nonspatial computer game. All of
      the children subsequently performed the direction estimation test again.
      Performance in direction estimation did not differ between the preliminary test
      and the posttest. Thus, in contrast to the parallel study with adults, the "small
      scale spatial ability" was not associated with "large-scale ability."

PMID- 20037989
TI  - Grip strength performances by 5- to 19-year-olds.
AB  - Accurate measures of muscular strength can yield insights about children's growth
      and development. The purpose of this study was to examine grip strength
      performances by boys and girls ages 5 to 19 years. A Jamar dynamometer was used
      to measure grip strength by 736 boys and girls ages 5 to 19 years. Multiple
      regression equations were applied to analyze the data. Overall, age-sex trends
      were similar to previous reports as boys and girls increased their performances
      across age levels. After age 12, boys' mean grip strength increased at a faster
      rate than girls'. However, participants in the present study performed better in
      the upper age ranges (13-19 yr.) than did boys and girls tested a generation ago.
      Potential associations between activity choices and grip strength are discussed.

PMID- 20037990
TI  - Sex differences found in facial EMG activity provoked by viewing pleasant and
      unpleasant photographs.
AB  - 50 male and 50 female participants' facial electromyographic (EMG) activity at
      the left corrugator and zygomatic muscle regions and self-reports of emotions
      were recorded while they were viewing Pleasant and Unpleasant photographs.
      Analysis showed that the ratio of EMG power between the periods of photograph
      viewing and baseline at the zygomatic muscle region was significantly higher than
      that at the corrugator muscle region while viewing Pleasant photographs and that
      the EMG ratio at the corrugator muscle region was significantly higher than that
      at the zygomatic muscle region while viewing Unpleasant photographs. Further
      analysis indicated that compared to men, women reported relatively higher
      feelings of pleasantness and generated significantly higher EMG ratios at the
      zygomatic muscle region while viewing Pleasant photographs and women reported
      significantly less feelings of pleasantness and generated significantly higher
      EMG ratios at the corrugator muscle region while viewing Unpleasant photographs.
      These results demonstrate the sex effects on emotion expression and associated
      EMG responses while viewing emotion provoking photographs.

PMID- 20037991
TI  - An investigation of home disadvantage in Davis Cup tennis.
AB  - Occurrence of the home disadvantage in Davis Cup tennis matches was examined by
      analyzing the outcome of Davis Cup finals matches from 1900 to 2007. There was no
      significant home disadvantage when Matches 1 and 2 were compared with Matches 4
      and 5. However, there was a significant home disadvantage when Matches 1 and 2
      were compared with Match 5. These findings are compared with those from earlier
      studies in which data from professional basketball and baseball were examined.

PMID- 20037992
TI  - Birth order and selection for university education in Kenya.
AB  - The representation of firstborns among 1,293 (650 women, 643 men) university
      freshmen in Kenya (M age = 20.8 yr., SD = 1.9) was explored. In a situation where
      university admission is very competitive, it was hypothesized that firstborns
      would be numerically more represented than later borns. The results indicated (a)
      an overall preponderance of the firstborns (20%), (b) only children and lastborns
      were the least represented groups at 1 and 5%, respectively, and (c) firstborns
      tended to come from relatively smaller families than the later borns. The
      findings were discussed in relation to previous studies, family size, and
      implications for future research in a subsistence society.

PMID- 20037993
TI  - Handedness correlates with actigraphically measured sleep in a controlled
      environment.
AB  - The relationship between hand preference and duration of sleep was assessed in 40
      healthy subjects using self-report estimates, sleep diaries, and wrist activity
      monitors during an uncontrolled 7-day at-home phase and during a controlled
      overnight stay in a sleep laboratory. Handedness was unrelated to any index of
      sleep duration when assessed in the unregulated home environment. In the
      controlled environment of the laboratory, however, greater right-hand dominance
      was positively correlated with more minutes of obtained sleep and greater sleep
      efficiency. Findings were consistent with previous reports which suggest measures
      of brain lateralization may be related to sleep and health but further suggest
      that these relationships may be easily obscured by extraneous environmental
      factors when assessed in an uncontrolled setting.

PMID- 20037994
TI  - School violence: evaluation and proposal of teaching staff.
AB  - The aim of this work was to evaluate the frequency of violent behaviors in
      educational centers, according to self-report of the teaching staff. To that end,
      a questionnaire about school violence was administered to a sample of 616
      teachers working in primary and secondary schools in Galicia, Spain. Disruptive
      and antisocial behaviors in the student population were reported to affect the
      teaching effort negatively. The compiled data indicate verbal aggression is the
      most common form of violence used by the student population and reveal the
      dissatisfaction of teaching staff not prepared for this challenge. Teachers felt
      the need to devise new effective responses to promote concord in educational
      communities.

PMID- 20037995
TI  - Competitive anxiety in expert female athletes: sources and intensity of anxiety
      in National Team and First Division Spanish basketball players.
AB  - State and trait anxiety levels in elite Spanish women basketball players were
      investigated and possible differences in sources of anxiety identified, comparing
      National Team and First Division players. 84 players participated (13 National
      Team members, 71 First Division players). A quantitative/qualitative design was
      used. Results indicated that National Team members had lower State and Trait
      Anxiety scores than did the First Division players and both groups had lower
      scores than established population norms. Playing time was significantly related
      to State and Trait Anxiety for both groups of players and those who had more
      minutes of playing time had lower scores. Qualitative analyses indicated that the
      primary sources of anxiety reported by these athletes related to personal issues
      pertaining to feeling physically and mentally unprepared for practice and games.

PMID- 20037996
TI  - Self-efficacy, foreign language anxiety as predictors of academic performance
      among professional program students in a general English proficiency writing
      test.
AB  - Questionnaires were administered to 120 students. Cluster analysis was used to
      examine whether specific groups could be described by a writing self-efficacy
      scale, English writing anxiety scale, and a written General English Proficiency
      Test. Three clusters were observed. Demographic variables were compared for each
      cluster, including age, sex, program of study, years of English instruction,
      native language, and number of English speaking acquaintances. Efforts to reduce
      writing anxiety and promote writing self-efficacy could enhance writing scores of
      participants.

PMID- 20037997
TI  - Deliberate practice theory: perceived relevance, effort, and inherent enjoyment
      of music practice: study II.
AB  - This study, based on the theory of deliberate practice, examined the practice
      relevance, effort, and inherent enjoyment aspects of the theory. 25 college
      undergraduates practiced playing a melody on an electronic keyboard for three 20
      min. practice sessions. Following each session, the perceived relevance of the
      practice for improving performance of the melody, the effort needed to learn the
      melody, and the inherent enjoyment of the practice were each rated on 10-point
      scales. Findings were consistent with theory and similar to previous studies also
      involving music practice and other tasks.

PMID- 20037998
TI  - Obstacle stepping and body scale modulating parameters.
AB  - The purpose of this study was to investigate gait spatial parameters at the point
      of departure, with obstacle heights adjusted to individual body scale.
      Undergraduate student volunteers (M age = 22.4 yr., SD = 2.1; 6 women, 1 man)
      were asked to step once, then cross over an obstacle and stop. This behavior was
      video recorded to extract kinematic data. The obstacle heights corresponded to
      high (knee-height) and low obstacles (half the knee-height). Points of departure
      corresponded to far (length of the lower limb) and close (half the length of the
      lower limb). The close point of departure influenced the trailing foot's
      placement ahead of the obstacle as well as step length. The high obstacle
      influenced the trailing foot's toe clearance. An interaction between factors was
      observed for leading foot toe clearance. Results indicate that body scale
      affected the participants' locomotor behavior during the obstacle-avoidance task.

PMID- 20037999
TI  - Classical illusions from parallel line figures: evidence for interactions among
      length-coding neurons.
AB  - Variations of the Craik-O'Brien, Muller-Lyer, reversed Muller-Lyer, orthogonal
      Muller-Lyer, and Ponzo illusions were created using 10 to 12 parallel lines. 20
      participants judged which of two physically equal lines in the patterns appeared
      longer. For 4 of the 5 patterns, the parallel lines created illusions which
      corresponded to those produced by the template figures. The results suggest that
      length is encoded by frequency of neural response and that the parallel line
      illusions, as well as their classical counterparts, emerge from interactions
      which distort this frequency code.

PMID- 20038000
TI  - Self-assessed tactical skills in elite youth soccer players: a longitudinal
      study.
AB  - Self-assessed tactical skills were investigated among 191 youth soccer players
      from ages 14 through 18 playing in different field positions. On a yearly basis,
      all players completed the Tactical Skills Inventory for Sports with scales for
      attacking and defensive situations and for declarative and procedural knowledge.
      A model to assess whether tactical skills change over time in each field position
      was developed using multilevel analysis. The models indicated that defenders and
      midfielders did not improve their tactical skills, whereas attackers increased
      their tactical skills from ages 14 to 18 years. The representing part of tactical
      skills for defenders is Acting in Changing Situations, for midfielders
      Positioning and Deciding, whereas Knowing About Ball Actions was the qualifying
      factor for attackers. Possible explanations for these differences in tactical
      skills among elite youth soccer players are the selection procedures at a younger
      age and task-specific experiences.

PMID- 20038001
TI  - Skills and offensive tactics used in pick-up basketball games.
AB  - The purpose of this study was to describe skills and offensive tactics frequently
      used in pick-up basketball games. 65 participants were recruited from public
      basketball courts. An observational instrument was developed to analyze the
      performances of pick-up games. Participants' performances were videotaped and
      coded. Results indicated that the passing skills most frequently observed in the
      games were chest pass, overhead pass, and bounce pass. For dribbling, crossover
      dribble and change-of-pace dribble were frequently observed. Jump shot, set shot,
      and layup were also frequently used. The offensive tactics frequently used
      included drive, cut, and set screen. The study may be beneficial for helping
      young people prepare to play pick-up basketball games.

PMID- 20038002
TI  - A technology-based stimulation program to reduce hand mouthing by an adolescent
      with multiple disabilities.
AB  - This study assessed the possibility of reducing hand mouthing, i.e., bringing
      fingers into or over the mouth, by an adolescent with multiple disabilities
      through a technology-based stimulation strategy. The strategy ensured that (a)
      the participant received 10 sec. of preferred stimulation contingent on the
      response of bringing both hands into a box with objects, and (b) the stimulation
      would be interrupted prematurely if the participant removed one or both hands
      from the box for 2 sec. The study involved an ABAB sequence (in which A
      represented baseline and B intervention phases) and a 3-mo. postintervention
      check. Data showed that the response of bringing both hands into the box
      increased from a mean frequency of about four per 10-min. session during baseline
      to a mean frequency of over 30 per session during the second intervention phase
      and the postintervention check. During these periods, the participant's mean hand
      mouthing time per session was below 1.5 min. (compared to above 7 min. during
      baseline) and the mean stimulation time per session was about 4 min. Practical
      implications of the findings are discussed.

PMID- 20038003
TI  - Exploring new compounds for functional imaging using a crayfish (Procambarus
      clarkia) aggression paradigm.
AB  - Covalently bonding multiple fluorine atom tags to the precursors of monoamines
      could provide compounds for functional imaging. Theoretically, the fluorine atoms
      can produce detectible signal if concentrated in vesicles inside neurons. Prior
      to committing more costly resources to the project, evidence was sought for
      uptake of the molecules into neurons in living organisms. Two 19F tag
      configurations of seven or nine atoms were investigated. Crayfish aggression
      provided a paradigm for obtaining preliminary data on the scarce new molecules.
      After establishing that 5-hydroxytryptophan (5-HTP) elicited serotonin-like
      effects, the fluorine tagged versions (PF-5-HTP) were investigated; then, the
      elevated aggression produced by these precursors to serotonin was blocked by
      coadministering fluoxetine. Treatment order effects and interrater reliability of
      the behavioral inventory were evaluated. Preliminary evidence that these imaging
      compounds are taken up into neurons obtained by studying crayfish behavior later
      found support using more sophisticated neuroscience techniques.

PMID- 20038004
TI  - Preparatory EMG activity reveals a rapid adaptation pattern in humans performing
      landing movements in blindfolded condition.
AB  - The main questions addressed in this work were whether and how adaptation to
      suppression of visual information occurs in a free-fall paradigm, and the extent
      to which vision availability influences the control of landing movements. The
      prelanding modulation of EMG timing and amplitude of four lower-limb muscles was
      investigated. Participants performed six consecutive drop-landings from four
      different heights in two experimental conditions: with and without vision.
      Experimental design precluded participants from estimating the height of the
      drop. Since cues provided by proprioceptive and vestibular information acquired
      during the first trials were processed, the nervous system rapidly adapted to the
      lack of visual information, and hence produced a motor output (i.e., prelanding
      EMG modulation) similar to that observed when performing the activity with vision
      available.

PMID- 20038005
TI  - Whole and part practice: a meta-analysis.
AB  - Motor learning textbooks provide specific recommendations for the use of whole
      and part practice during motor skill acquisition. Magill recommended basing
      decisions on Naylor and Briggs' hypothesis of task complexity and organization,
      while Schmidt and Wrisberg recommended basing decisions on skill classification.
      To evaluate the accuracy of these recommendations, a meta-analysis was conducted.
      Through a literature search, 44 articles were located, and 20 provided sufficient
      information to calculate effect sizes. Effect sizes were calculated using means
      for whole and part practice for acquisition and retention. Although several
      analyses were compromised by insufficient studies investigating whole and part
      practice, mean effect sizes generally supported motor learning textbooks. To
      better verify the empirical validity of recommendations for the use of whole and
      part practice, more studies are necessary.

PMID- 20038006
TI  - Economic and cultural correlates of road-traffic accident fatality rates in OECD
      countries.
AB  - The relationships between economic conditions, cultural characteristics,
      personality dimensions, intelligence scores, and road-traffic accident mortality
      rates were investigated in 30 member and five accession countries of the
      Organisation for Economic Co-operation and Development (OECD). Economic
      indicators included the Gross Domestic Product (GDP) per capita, the unemployment
      rate, and the Gini index. Cultural variables included five Hofstede's cultural
      dimensions, seven Schwartz cultural value dimensions, NEO-PI-R scales, and the
      intelligence quotient (IQ). The results showed positive associations between
      favorable economic conditions (high income per capita, high employment rate, and
      low income inequality) and high traffic safety. Countries with higher road
      traffic accident fatality rates were characterized by higher power distance and
      uncertainty avoidance as well as embeddedness and emphasis on social hierarchy.
      Countries with lower road-traffic accident fatality rates were more
      individualistic, egalitarian, and emphasized autonomy of individuals.
      Conscientiousness (from NEO-PI-R) and IQ correlated negatively with road-traffic
      accident fatalities.

PMID- 20038007
TI  - Human signal-detection performance in multiscreen monitoring tasks.
AB  - Human monitoring performance was compared for different screens within a single
      display. Participants' performance with random signals and different numbers of
      split screens was tested for a period of time. The performance measures were hit
      rate, false alarm rate, and response time. Results indicated that the response
      time and false alarm rate significantly increased with the number of split
      screens. Results also showed that signal frequency significantly influenced the
      false alarm rate. The location of the 9-screen display was analyzed on hit rate
      and false alarm rate. More attention was paid to the center screen as indicated
      by both the higher hit rate and false alarm rate. Findings suggest that designers
      of monitoring systems should take into consideration the trade-off between the
      number of multiple split screens and the limited human capability for monitoring
      performance. Furthermore, it is suggested that high risk and critical information
      should be placed in the center region to be detected effectively.

PMID- 20038008
TI  - Sport fan identification in obituaries.
AB  - To assess whether sport involvement, particularly as a fan, is central enough to
      one's self-concept to be mentioned in obituary content, it was hypothesized that
      a greater proportion of men's obituaries than women's would mention the deceased
      individual's sport fan identification. Obituaries were randomly selected from 19
      newspapers and coded for specific affiliations (e.g., military) and involvement
      in leisure activities (e.g., sport participation). Consistent with the
      hypothesis, a chi-squared analysis indicated the men's obituaries (15.2%) were
      significantly more likely than the women's (5.2%) to mention sport fan
      identification. A higher proportion of the men's obituaries (24.4%) mentioned
      sport participation than the women's obituaries (7.4%).

PMID- 20038009
TI  - Visuomotor control of straight and breaking golf putts.
AB  - This study assessed golfers' gaze behavior in both the preparation (line reading)
      and execution (ball striking) of putts with different break characteristics. Six
      golfers completed 25 3-m putts on five different slopes (flat, 0.9 degrees and
      1.8 degrees left-to-right, 0.9 degrees and 1.8 degrees right-to-left), while
      their gaze behavior was analyzed using an Applied Science Laboratories Mobile Eye
      gaze-registration system. Frame-by-frame analyses of 136 putts were performed to
      assess the number and duration of fixations made during the preparation and
      execution phases of the putts. Putting performance was significantly poorer for
      the most severe break (1.8 degrees) than for other conditions. The only gaze
      variable to distinguish between successful and unsuccessful putting outcome was
      the quiet eye period (the final fixation prior to the initiation of the putter
      movement). Specifically, participants had significantly longer quiet eye periods
      on successful than on unsuccessful putts.

PMID- 20038010
TI  - Performance on psychomotor tasks following two yoga-based relaxation techniques.
AB  - Previously cyclic meditation and supine rest have been shown to improve
      performance in a letter cancellation task requiring attention, visual scanning,
      and motor speed. The present study assessed the performance in 57 volunteers (all
      male, M age = 26.5 yr., SD = 4.6) in three tasks, viz., a digit-letter
      substitution task (DLST), a letter-copying task, and a circle-dotting task. The
      DLST assessed attention and speed of information processing, while the other 2
      tests assessed motor speed. Each participant was assessed before and after three
      types of sessions: Cyclic Meditation, Supine Rest, and Control (no intervention).
      DLST scores and scores for letter-copying and circle-dotting tasks improved
      significantly after cyclic meditation; the same scores also improved after supine
      rest. There was no change after the no-intervention/Control session. From the
      results it was difficult to conclude whether improved DLST scores after cyclic
      meditation were due to better information processing speed or improved motor
      speed.

PMID- 20038011
TI  - Replicating a simple study of asymmetry in human cognition.
AB  - V. A. Lefebvre proposed an algebraic model of self-reflexion in the 1980s, and
      one of the model's central predictions was that individuals would exhibit a clear
      asymmetry in their judgments when facing an ambiguous binary choice task. A
      replication of the results of a 1990 test of Lefebvre's model was attempted by
      asking individuals to sort pairs of pinto beans into boxes marked as either
      "good" or "bad." Consistent with the model's predicted frequency of .618, the
      participants judged the beans to be good with an average frequency of .624. This
      result was also significantly higher than the frequency expected from random
      judgments (viz., .50).

PMID- 20038012
TI  - Target difficulty, priority assignment of attentional resources, foveal task
      load, and order of testing of foveal loading on visual lobe shape
      characteristics.
AB  - Effects of the difficulty of a peripheral target, the priority assignment of
      attentional resources for simultaneous peripheral and foveal tasks, and the
      foveal task load and order of testing of cognitive foveal loadings on visual lobe
      shape characteristics were investigated. Analysis showed that lobe shape
      characteristics were affected by target difficulty but not the low foveal load.
      For the tasks used here, attentional resources were sufficient for participants
      to perform both peripheral and foveal tasks concurrently; therefore, priority
      assignment of attentional resources had no effect on lobe shape. With regard to
      order of testing of foveal loading, lobe roundness, boundary smoothness, and
      vertical symmetry improved with a positive practice effect for the groups tested
      in the high level-low level order. The implication is that providing training or
      practice to participants on a task with a higher level foveal load could optimize
      lobe roundness, boundary smoothness, and symmetry. Performance on the foveal task
      was better with easy peripheral targets than difficult targets and better for the
      foveal-primary than for the peripheral-primary conditions, presumably because of
      the larger proportion of attentional resources allocated to the foveal task for
      these two groups.

PMID- 20038013
TI  - Cognitive complexity and personality.
AB  - For 49 college students, cognitive complexity as measured by George Kelly's REP
      Grid technique was associated with Judging-Perceiving scores on the Keirsey-Bates
      Temperament Sorter.

PMID- 20038014
TI  - Effects of color combination and ambient illumination on visual perception time
      with TFT-LCD.
AB  - An empirical study was carried out to examine the effects of color combination
      and ambient illumination on visual perception time using TFT-LCD. The effect of
      color combination was broken down into two subfactors, luminance contrast ratio
      and chromaticity contrast. Analysis indicated that the luminance contrast ratio
      and ambient illumination had significant, though small effects on visual
      perception. Visual perception time was better at high luminance contrast ratio
      than at low luminance contrast ratio. Visual perception time under normal ambient
      illumination was better than at other ambient illumination levels, although the
      stimulus color had a confounding effect on visual perception time. In general,
      visual perception time was better for the primary colors than the middle-point
      colors. Based on the results, normal ambient illumination level and high
      luminance contrast ratio seemed to be the optimal choice for design of workplace
      with video display terminals TFT-LCD.

PMID- 20038015
TI  - [Monitoring of oxygen concentration based on tunable diode laser absorption
      spectroscopy].
AB  - Oxygen is a widely used important gas in the industrial process. It is very
      meaningful to on-line monitor the oxygen concentration for the enhancement of
      combustion efficiency and reduction in environmental pollution. Tunable diode
      laser absorption spectroscopy (TDLAS) is a highly sensitive, highly selective and
      fast time response trace gas detection technique. With the features of tunability
      and narrow linewidth of distributed feedback (DFB) diode laser and by precisely
      tuning the laser output wavelength to a single isolated absorption line of the
      gas, TDLAS technique can be utilized to accurately implement gas concentration
      measurement with very high sensitivity. In the present paper, the authors used a
      DFB laser was used as the light source, and by employing wavelength modulation
      method and measuring the second harmonic signal of one absorption line near 760
      nm of oxygen molecule, the authors built a system for online monitoring of oxygen
      concentration. The characteristics of the system are as follows: the scope of
      detection is 0.01%-20%; detection accuracy is 0.1%, long term stability is 1%.

PMID- 20038016
TI  - [Ammonia gas concentration and velocity measurement using tunable diode laser
      absorption spectroscopy and optical signal cross-correlation method].
AB  - Simultaneous online measurement of gas concentration and velocity can be realized
      by tunable diode laser absorption spectroscopy (TDLAS) technique and optical
      signal cross-correlation method. The fundamental and relative factors of gas
      concentration and velocity measurement are described in the present paper. The
      spectral lines of NH3 used for gas sensing at communication band in near infrared
      range were selected and analyzed by the calculation based on the HITRAN database.
      In the verification experiment, NH3 and N2 were mixed by two mass flow meters and
      sent to flow through the quartz tube 0. 016 m in inner diameter and 1 m in length
      at normal temperature and pressure. The spectral line located at 6,548.7 cm(-1)
      was scanned at high frequency by the diode laser of 15 MHz linewidth and 1 cm'
      tunable range with no mode hoppings. The instantaneous NH3 absorbance was
      obtained using direct absorption method and the gas concentration was calculated.
      At the same time, the non-intrusive optical absorption signal cross-correlation
      method was utilized to obtain two concentration signals from two adjacent
      detectors mounted along the gas tube. The corresponding transit time of gas
      passing through the detectors was calculated by cross-correlation algorithm, and
      the average gas velocity was inferred according to the distance between the two
      detectors and the transit time. The relative errors were less than 7% for the gas
      concentration measurement, and less than 10% for the gas velocity measurement.
      Experimental results were proved to be of high precision and good repeatability
      in the lab. The feature of fast response and capacity immune to the in situ
      disturbance would lead to a potential in industry application for the real time
      measurement and control of gas pollutant emission in the future.

PMID- 20038017
TI  - [Comparison of two spectral mixture analysis models].
AB  - A spectral mixture analysis experiment was designed to compare the spectral
      unmixing effects of linear spectral mixture analysis (LSMA) and constraint linear
      spectral mixture analysis (CLSMA). In the experiment, red, green, blue and yellow
      colors were printed on a coarse album as four end members. Thirty nine mixed
      samples were made according to each end member's different percent in one pixel.
      Then, field spectrometer was located on the top of the mixed samples' center to
      measure spectrum one by one. Inversion percent of each end member in the pixel
      was extracted using LSMA and CLSMA models. Finally, normalized mean squared error
      was calculated between inversion and real percent to compare the two models'
      effects on spectral unmixing. Results from experiment showed that the total error
      of LSMA was 0.30087 and that of CLSMA was 0.37552 when using all bands in the
      spectrum. Therefore, LSMA was 0.075 less than that of CLSMA when the whole bands
      of four end members' spectra were used. On the other hand, the total error of
      LSMA was 0.28095 and that of CLSMA was 0.29805 after band selection. So, LSMA was
      0.017 less than that of CLSMA when bands selection was performed. Therefore,
      whether all or selected bands were used, the accuracy of LSMA was better than
      that of CLSMA because during the process of spectrum measurement, errors caused
      by instrument or human were introduced into the model, leading to that the
      measured data could not mean the strict requirement of CLSMA and therefore
      reduced its accuracy: Furthermore, the total error of LSMA using selected bands
      was 0.02 less than that using the whole bands. The total error of CLSMA using
      selected bands was 0.077 less than that using the whole bands. So, in the same
      model, spectral unmixing using selected bands to reduce the correlation of end
      members' spectra was superior to that using the whole bands.

PMID- 20038018
TI  - [Effect of ambient atmosphere on laser micro-plasma radiant intensity].
AB  - The plasma radiant intensity was investigated by a laser micro-plasma spectral
      analysis system. The system consists of an YJG-II laser micro-spectral analyzer
      and a CCD data acquisition and processing system. National standard soil samples
      were studied in the experiment under different ambient atmosphere with argon,
      helium and the mixture of argon and helium by using the analysis lines, Ca II
      393.367 nm and Ca II 396.847 nm. The results of this research suggest that both
      the time of plasma illumination and the radiant intensity of plasma in an
      atmosphere of helium-argon mixture were better than that in pure helium or argon
      gas. The plasma radiant intensity was obviously enhanced when the proportion of
      helium and argon was 66.7% and 33.3%, respectively. Under these conditions, the
      influence of the height of auxiliary electrode on laser micro-plasma radiant
      intensity was also investigated. The maximum laser micro-plasma radiant intensity
      was reached when the height of auxiliary electrode was 3 mm.

PMID- 20038019
TI  - [Temperature dependence of cross sections for energy transfer processes of Rb(7S
      5D)-H2, He].
AB  - Rb vapor, mixed with H2 or He, was irradiated in a glass fluorescence cell with
      pulses of radiation from a YAG-laser-pumped OPO laser, populating 5D or 7S state
      by two-photon absorption. The temperature dependence of the cross sections for 5D
      7S transfer induced by collisions with He atoms and H2 molecules was determined
      using methods of atomic fluorescence. The resulting fluorescence included a
      direct component emitted in the decay of the optically excited state and a
      sensitized component arising from the collisionally populated state. At the
      different densities, the authors have measured the relative time-integrated
      intensities of the components and fitted a three-state rate equation model to
      obtain the reactive and nonreactive cross sections for Rb(7S-5D)-H2, He
      collisions. The cross sections of transfer for Rb(7S)+H2-->Rb(5D)+H2 decrease
      with increasing T. The cross sections for 5D-->7S increase with increasing T. At
      the different temperatures, the cross sections of transfer for (7S-5D)-He
      collisions coincide with the principle of detailed balance. The total transfer
      rate coefficients out of the 7S or 5D state for He were small. The total
      quenching rate coefficient out of the 7S or 5D state was much larger for H2. In
      the case of H2, the quenching rate coefficient corresponds to reaction and
      nonreactive energy transfer. In reaction of Rb(7S, 5D)+H2-->RbH+H, the ratio
      between the reactive cross sections was found to be sigma(-)[Rb(7S)+H2]/sigma(
      )(Rb(5D)+H2]=1.5. The relative reactivity with H2 was in an order of
      Rb(7S)>Rb(5D).

PMID- 20038020
TI  - [Application of immunomagnetic separation to E. coli O157 : H7 detection].
AB  - In the present paper, the capture efficiencies of four different proportions of
      E. coli O157 : H7 and immunomagnetic beads (IMB) (1 : 6.34, 1 : 12.69, 1 : 25.38
      and 1 : 30.07) and three different proportions of E. coli O157 : H7 and Bacillus
      subtilis (0.3 mL : 0.1 mL, 0.2 mL : 0.2 mL and 0.1 mL : 0.3 mL) were compared,
      with the total volume and capacity of IMB remaining constant. It was revealed
      that the capture efficiency could reach 100% when the proportion of E. coli O157
      : H7 and IMB was 1 : 30, meaning that almost all targets E. coli O157 : H7 could
      be captured at 1 : 30, and that the capture efficiency decreased and then
      increased with the number of Bacillus subtilis increasing. Moreover, the
      combination of ATP bioluminescence and IMS was correlated well with conventional
      culture methods, R2 = 0.9882, and the detection limit was as low as 10(2) CFU x
      mL(-1).

PMID- 20038021
TI  - [Investigation of guanidine hydrochloride induced chlorophylls denaturation by
      terahertz time-domain spectroscopy].
AB  - In investigating guanidine hydrochloride (GuHCl) denatured chlorophylls using the
      terahertz time-domain spectroscopy, the authors explored the feasibility and
      sensitivity of the terahertz technology in sensing protein denaturation and
      associated conformation changes. It was found that the conformation change was
      induced by the C=O group of chlorophyll, interacting with the N-H group of GuHCl
      to form hydrogen bonds, which shows higher absorption than the native ones and an
      absorption peak around 1.7 THz in our THz spectra. The results presented here
      demonstrate that THz-TDS has both advantages and disadvantages in monitoring
      denaturation process of proteins, which is important in applying THz-TDS
      technique to the study of biomolecules.

PMID- 20038022
TI  - [Terahertz spectroscopic investigation of organophosphorus pesticide parathion
      methyl].
AB  - The present paper reports the theoretical and experimental vibrational spectra of
      organophosphorus pesticide parathion-methyl in the frequency range from 0.2 to
      2.0 THz respectively. Under the room temperature and nitrogen conditions, the
      absorption peaks were found at 0.65, 1.33, 1.81 and 1.91 THz, and the average
      refractive index was 1.39 based on the terahertz time-domain spectroscopy (THz
      TDS). In parallel with the experimental study, density functional theory (DFT)
      was applied to obtain the structure and vibrational frequencies of parathion
      methyl in the terahertz region. The calculated results are in reasonable
      agreement with the experimental data. The absorption features are caused by the
      collective vibrational and torsional modes, and the different absorption peaks
      correspond to different vibrational modes.

PMID- 20038023
TI  - [Study on the sensitizing effect of fac-tris(2-phenylpyridinato-N, C2') iridium
      (III) on two different fluorescent materials].
AB  - It is considered that the efficiency of fluorescent material based organic light
      emitting diodes can be enhanced by introducing a phosphorescent sensitizer. In
      the present work, devices with emission layers (EML) of fac-tris(2
      phenylpyridinato-N, C2') iridium (III) (Ir(ppy)3)-sensitized-fluorescent
      materials were fabricated. Ir(ppy)3 was co-doped with DCJTB and rubrene in PVK
      matrix, respectively. When the doping ratio was proper, pure emission from
      fluorescent material can be achieved. Furthermore, the sensitizing mechanism and
      effect were analyzed. A weak effect between Ir(ppy)3 and DCJTB was found. It was
      deduced that the weaker sensitizing effect is related to the poor film
      appearance.

PMID- 20038024
TI  - [The general analytical methods for gases dissolved in liquids:
      sonoluminescence].
AB  - How to analyze the gases dissolved in water or organic liquids is a challenging
      problem in analytical chemistry. Till the present time, only the dissolved oxygen
      in water can be analyzed by chemical and instrumental methods, while other gases,
      e. g. CO2, N2, CH4, Ar, He, Ke, still can not be analyzed by chemical or
      instrumental methods. The present paper gives a review on using sonoluminescence
      for gas analysis in water or organic liquids.

PMID- 20038025
TI  - [Development of an analyzing system for soil parameters based on NIR
      spectroscopy].
AB  - A rapid estimation system for soil parameters based on spectral analysis was
      developed by using object-oriented (OO) technology. A class of SOIL was designed.
      The instance of the SOIL class is the object of the soil samples with the
      particular type, specific physical properties and spectral characteristics.
      Through extracting the effective information from the modeling spectral data of
      soil object, a map model was established between the soil parameters and its
      spectral data, while it was possible to save the mapping model parameters in the
      database of the model. When forecasting the content of any soil parameter, the
      corresponding prediction model of this parameter can be selected with the same
      soil type and the similar soil physical properties of objects. And after the
      object of target soil samples was carried into the prediction model and processed
      by the system, the accurate forecasting content of the target soil samples could
      be obtained. The system includes modules such as file operations, spectra
      pretreatment, sample analysis, calibrating and validating, and samples content
      forecasting. The system was designed to run out of equipment. The parameters and
      spectral data files (*.xls) of the known soil samples can be input into the
      system. Due to various data pretreatment being selected according to the concrete
      conditions, the results of predicting content will appear in the terminal and the
      forecasting model can be stored in the model database. The system reads the
      predicting models and their parameters are saved in the model database from the
      module interface, and then the data of the tested samples are transferred into
      the selected model. Finally the content of soil parameters can be predicted by
      the developed system. The system was programmed with Visual C++6.0 and Matlab
      7.0. And the Access XP was used to create and manage the model database.

PMID- 20038026
TI  - [Selection of variables for MLR in Vis/NIR spectroscopy based on BiPLS combined
      with GA].
AB  - The feasibility of using efficient selection of variables in Vis/NIR for a rapid
      and conclusive determination of fruit inner qualities such as soluble solids
      content (SSC) of plums was investigated. A new strategy was proposed in the
      present paper, i. e. two-stage variable selection using the backward interval
      partial least squares (BiPLS) combined with genetic algorithm (GA). Firstly, it
      splits the whole spectral region into equidistant sub-regions and then develops
      all BiPLS regression models, and the informative regions which are used to
      constructed PLS models with the lowest error can be located. Secondly, GA method
      is used to select variable in these informative regions, which are used for
      regression variables of MLR model. The Vis/NIR spectra containing 225 individual
      data points were processed by Savizky-Golay filter smoothing and second-order
      derivative, and 9 sub-regions were selected by BiPLS procedure when the spectra
      were divided into 25 sub-regions. The optimal 12 variables, which were the output
      of the GA procedure, were selected by the higher occurrence frequency while the
      GA procedure ran 100 times. In order to simplify the multiple linear regression
      (MLR) modeling, the wavelength variables with the maximum occurrence frequency
      were chosen when the adjacent wavelengths were selected by GA. Finally, 638, 734,
      752, 868, 910, 916 and 938 nm were used to build a MLR model. The results show
      that MLR model produced by BiPLS-GA performs well with correlation coefficients
      (R) of 0.984, root mean standard error of calibration (RMSEC) of 0.364 and root
      mean standard error of prediction (RMSEP) of 0.471 for SSC, which outperforms
      models using stepwise regression analysis (SRA). This work proved that the BiPLS
      GA could determine optimal variables in Vis/NIR spectra and improve the accuracy
      of model.

PMID- 20038027
TI  - [Effect of different tillage managements on black humic fractions and IR spectral
      feature].
AB  - The present study was based on the long-term (10 years) field conservation
      tillage experiment, in which four tillage treatments were designed as following:
      Conventional tillage (CT) by moldboard plowing with ridge culture; Rotary tillage
      with ridge culture (RT); Alternant tillage by rotary on wide row and loosing on
      narrow row (WN); Rotary tillage plus deep loosing annually (RD). Humic acids were
      extracted from black soil profiles under these tillage managements. The elements
      visible spectra and FTIR of HA in black soil were analyzed. The results indicated
      that the elements of HA were affected by different tillage managements, WN
      increased N/C, H/C and O/C values of HA in the 0-20 cm layer. The lowest E4/E6
      value of HA was found under CT treatment, while the highest E4/E6 value was found
      under WN treatment; FTIR indicated that CT treatment increased the amount of C=N
      groups and aromatic ring condensation of HA in 0-20 cm soil, while WN decreased
      aromatic ring condensation and increased the content of nitrogen compound and
      aliphatic compound. RT increased the functional groups of OH, aliphatic CH2 and
      nitrogen compound. CT and RD increased the content of C=O and C-O.

PMID- 20038028
TI  - [Identification and analysis of rice drought tolerance using near infrared
      diffuse reflection spectra of leaves].
AB  - In the present study, different drought tolerance rice from different countries
      and areas were selected and grown in water field and drought field respectively,
      including 4 traditional varieties of drought rice, 18 varieties of modified
      drought rice, 2 varieties of drought traits rice, 2 varieties of drought
      tolerance rice, and a total of 30 different varieties of drought tolerance rice
      were involved. Using near infrared diffuse reflection spectra of leaves from
      water field and drought field, we studied the rice drought tolerance
      identification analysis. Results showed that: using the average spectra of
      several leaves' spectra, selecting 4,500-7,500 cm(-1) as effective analysis
      spectra zone, choosing the first derivative and multiple scattering correction
      (MSC) as spectra preprocessing method, we can set up the calibration models
      between the spectra of leaves from drought field and the yield of rice.
      Simultaneously, we concluded that the performance of calibration model for rice
      yield and drought tolerance identification indexes in the upper booting stage was
      better than in the previous booting stage whose correlation coefficient of cross
      validation could reach 0.8. But there was no obvious relation between the spectra
      from water field and the yield, the drought tolerance identification indexes. We
      explained the difference in these two series models' performance from the
      relationship between some parameter of the leaves' biochemistry (chlorophyll,
      moisture, etc) and yield, the drought tolerance identification indexes.

PMID- 20038029
TI  - [Study on fixation mechanism of CuAz preservatives in bamboo by ATR-FTIR].
AB  - The fixation mechanism of CuAz preservatives in bamboo was studied with bamboo as
      the experimental material in the present paper. The purpose of the study is to
      understand the interaction between preservatives and bamboo, provide a
      theoretical basis for the design and optimization of preservatives formula and
      for improving preservative treatment. The chemical combination between
      preservatives and bamboo components was analysed by ATR Fourier transform
      infrared spectroscopy (ATR-FTIR), and the results show that the infrared spectra
      of lignin after treatment changed significantly. The lignin characteristic peaks
      (1,510 cm(-1)) changed obviously. Lignin phenolic hydroxyl was involved in the
      lignin-copper complex formation. Holocellulose's spectra after treatment changed
      little, with just a change in hemicellulose carboxyl and hemicellulose acyl
      oxygen bond (CO-O) stretching vibration.

PMID- 20038030
TI  - [Analysis of cell arrangements in Biota orientalis using Fourier transformation].
AB  - Fourier transform image-processing technology is applied for determining the
      cross section cell arrangement of early-wood in Biota orientalis. In this method,
      the disc-convoluted dot map from each cell radius with 10 pixels is transformed
      by Fourier transform, generating the angle distribution function in the power
      spectral pattern. The maximum value is the arrangement of the cell. The results
      of Fourier transform image-processing technology indicated that the arrangements
      of the cell of Biota orientalis are 15 degrees in oblique direction,
      respectively. This method provides a new basis for the digitized identification
      of the wood, and also the new theoretical research direction for the digitized
      identification and examination of the wood species.

PMID- 20038031
TI  - [Study on temperature measurement of solution by reference-wavelength method].
AB  - Near-infrared (NIR) spectroscopy has been widely used in agriculture, medicine,
      petrochemical and food industries. However, the measurement precision of NIR
      spectroscopy is adversely affected by the change in external conditions. Among
      these influence factors, temperature fluctuation is harder to be controlled than
      other conditions such as contact pressure and measurement position. Based on the
      displacement effect between solvent and solute molecules in solution, a reference
      wavelength method for temperature measurement of solution is presented in the
      present paper. The theoretical expression of the method was introduced. The
      experiment was designed to measure the spectra of glucose aqueous solution under
      different temperatures, and the effect of eliminating the temperature disturbance
      was evaluated. When the temperature and solute concentration of solution change
      simultaneously, the absorbency difference value at reference-wavelength is
      insensitive to solute concentration, and is totally affected by temperature
      fluctuation. Therefore, according to the absorbance difference, the actual
      temperature of the sample can be calculated. The regression model of temperature
      measurement was established, and the solution temperature was calculated based on
      this model. The information about temperature can be acquired exactly by
      reference-wavelength method, and the experimental results showed that the average
      error of calculated temperafure is 0.03 degree C.

PMID- 20038032
TI  - [Study on a method of selecting calibration samples in NIR spectral analysis].
AB  - In the present paper, a simple but novel method based on maximum linearly
      independent group was introduced into near-infrared (NIR) spectral analysis for
      selecting representative calibration samples. The experiment materials contained
      2,652 tobacco powder samples, with 1,001 samples randomly selected as prediction
      set, and the others as representative sample candidate set from which calibration
      sample set was selected. The method of locating maximum linearly independent
      vectors was used to select representative samples from the spectral vectors of
      representative samples candidate set. The arithmetic was accomplished by function
      rref(X,q) in Matlab. The maximum linearly independent spectral vectors were
      treated as calibration samples set. When different calculating precision q was
      given, different amount of representative samples were acquired. The selected
      calibration sample set was used to build regression model to predict the total
      sugar of tobacco powder samples by PLS. The model was used to analyze 1001
      samples in the prediction set. When selecting 32 representative samples, the
      model presented a good predictive veracity, whose predictive mean relative error
      was 3.6210%, and correlation coefficient was 0.9643. By paired-samples t-test, we
      found that the difference between the predicting result of model obtained by 32
      samples and that obtained by 146 samples was not significant (alpha=0.05). Also,
      we compared the methods of randomly selecting calibration samples and maximum
      linearly independent selection by their predicting effects of models. In the
      experiment, correspondingly, six calibration sample sets were selected, one of
      which included 28 samples, while the others included 32, 41, 76, 146 and 163
      samples respectively. The method of maximum linearly independent selecting
      samples turned out to be obviously better than that of randomly selecting. The
      result indicated that the proposed method can not only effectively enhance the
      cost-effectiveness of NIR spectral analysis by reducing the number of samples
      required for cockamamie and expensive chemical measurement, but also improve the
      analysis accuracy. In conclusion, this method can be applied to select
      representative samples in near-infrared spectral analysis.

PMID- 20038033
TI  - [Injection by near infrared diffuse reflectance spectroscopy].
AB  - In the present study, a total of 47 levofloxacin hydrochloride injection samples
      were detected by near infrared (NIR) spectroscopy, and 37 samples were randomly
      selected to establish the quantitative models by partial least squares (PLS) and
      artificial neural network (ANN) technology, while other 12 samples were used for
      prediction. On the one hand, the model was established by PLS, the coefficient of
      determination (R2) of the prediction is 0.964, and the root mean squared error of
      prediction (RMSEP) is 0.2428. On the other hand, after the spectrum variables
      were highly effectively compressed using the wavelet transformation technology,
      the quantitative analysis model of levofloxacin hydrochloride was established
      through the ANN technology. The R2 and RMSEP of the model is 0.944 and 0.5722,
      respectively. In this work, we have a detailed comparison between the two
      technologies in the progress of two quantitative models and optimizing
      correlative parameter, and finally we got a satisfied result. The simulation
      experiment indicated that the above PLS model is more steady and precise than ANN
      model, which can get hold of a rapid and nondestructive quantitative analysis
      result of the injection. Thus, the research can provide powerful scientific basis
      and technical support for further analysis of levofloxacin hydrochloride
      injection.

PMID- 20038034
TI  - [Identification of hardness of licorice single seed using near infrared
      spectroscopy].
AB  - To break the dilemma on judging hard seeds and soft seeds of licorice and other
      legume families nondestructively, a distinguishing model for the hardness of
      licorice single seed was tried to be built by near infrared reflectance
      spectroscopy with distinguished partial least squares(DPLS). A total of 244
      licorice seeds were divided into three groups: calibration set (120 samples),
      validation set (60 samples) and prediction set (64 samples), and each group has
      the same number of hard seeds and soft seeds. To eliminate the human error as far
      as possible, a specially made sample cup was designed for spectrum acquisition.
      Then the locations of the seed and the fiber-optic probe were fixed during each
      spectrum acquisition process. The influences of different replicate time,
      different spectral region and different calibration samples on the identification
      rate were compared. The result indicated that four replicates could increase the
      identification rate of the model significantly, the identification rates of the
      model of four replicates in calibration, validation and prediction set samples
      were 95.83%, 95.00% and 96.88% respectively, while that of one replicate were
      93.33%, 91.67% and 82.81% respectively. The model of the spectral region between
      4,000 and 80,000 cm(-1) was better than that of other regions, and the
      identification rate in calibration, validation and prediction set samples were
      95.53%, 95.94% and 94.53% respectively. Even with different samples, the
      predication rates were all more than 90%. The identification rates of hard seed
      and soft seed in prediction set samples were 92.50% and 96.56% respectively. The
      prediction for seeds with different size and different color showed that this
      model was not suitable for bigger and smaller seeds, especially not for black
      seeds. NIR offered a new way to distinguish the hardness of licorice singe seed
      quickly, precisely and nondestructively, which will advance the study on the
      mechanism of hardness of crop seeds.

PMID- 20038036
TI  - [Analysis of polysaccharides contents in Ophiopogon japonicus by NIR].
AB  - In the present paper the polysaccharides in Ophiopogon japonicus was analysed
      quantitatively by using near infrared spectroscopy. The spectral characteristics
      of the primary ingredients in ophiopogonis were obtained by applying first
      derivative, second derivative, smoothing, SNV (standard normal variate), and MSC
      (multiple scatter correction), and the wavelengths were selected for the best
      model. Meantime, in combination with the PLS algorithm the calibration process
      was performed for the quantitative analysis of the polysaccharides in Ophiopogon
      japonicus. The result showed that after optimizing all the factors, the best
      model of equation was using "first derivative" + "MSC" + "SG", and the
      wavelengths for the best model were selected in 4,000-4,900, 5,100-6,900 and
      7,050-10,000 cm(-1). The result showed a fine precision of the method, with R2,
      RMSEC, R2CV, RMSECV and principal factors being 0.996, 0.237, 0.973, 0.583 and 6,
      respectively. A set of representative samples were used to check the model, and
      the prediction coefficient of determination was 96.88%.

PMID- 20038035
TI  - [Determination of sinigrin in semen Thlaspi from Sichuan and Tibet using near
      infrared diffuse reflectance spectroscopy].
AB  - The objective of the present study was to develop a method for the determination
      of sinigrin in semen Thlaspi from Sichuan using near infrared diffuse reflectance
      spectroscopy. Near infrared spectra (NIR) in the region of 7,502.1-5,446.2 cm(-1)
      were recorded for the 246 semen Thlaspi samples containing sinigrin in the
      content of 1.962%-3.917%. Calibration models were established using the PLS
      (partial least squares). Different spectra pretreatment methods were compared.
      The study showed that spectral information can be extracted thoroughly by minimum
      and maximum normalization pretreatment methods. In this calibration model, the
      correlation coefficient (R2) was 0.9280, the SEC (standard deviation of the
      calibration sets) was 0.314 and the SEP (standard deviation of the prediction
      sets) was 0.388. Results indicated that near infrared diffuse reflectance
      spectroscopy method can be used to rapidly analyze the valid component in
      traditional Chinese medicine, and also can be used in the quality control of
      traditional Chinese medicine.

PMID- 20038037
TI  - [Detection of single-walled carbon nanotube bundles by tip-enhanced Raman
      spectroscopy].
AB  - Raman spectroscopy is a powerful technique in the characterization of carbon
      nanotubes (CNTs). However, this spectral method is subject to two obstacles. One
      is spatial resolution, namely the diffraction limits of light, and the other is
      its inherent small Raman cross section and weak signal. To resolve these
      problems, a new approach has been developed, denoted tip-enhanced Raman
      spectroscopy (TERS). TERS has been demonstrated to be a powerful spectroscopic
      and microscopic technique to characterize nanomaterial or nanostructures. Excited
      by a focused laser beam, an enhanced electric field is generated in the vicinity
      of a metallic tip because of the surface plasmon polariton (SPP) and lightening
      rod effect. Consequently, Raman signal from the sample area illuminated by the
      enhanced field nearby the tip is enhanced. At the same time, the topography is
      obtained in the nanometer scale. The exact corresponding relationship between the
      localized Raman and the topography makes the Raman identification at the
      nanometer scale to be feasible. In the present paper, based on an inverted
      microscope and a metallic AFM tip, a tip-enhanced Raman system was set up. The
      radius of the Au-coated metallic tip is about 30 nm. The 532 nm laser passes
      through a high numerical objective (NA0.95) from the bottom to illuminate the tip
      to excite the enhanced electric field. Corresponding with the AFM image, the tip
      enhanced near-field Raman of a 100 nm diameter single-walled carbon nanotube
      (SWNT) bundles was obtained. The SWNTs were prepared by arc method. Furthermore,
      the near-field Raman of about 3 SWNTs of the bundles was received with the
      spatial resolution beyond the diffraction limit. Compared with the far-field
      Raman, the enhancement factor of the tip-enhanced Raman is more than 230. With
      the super-diffraction spatial resolution and the tip-enhanced Raman ability, tip
      enhanced Raman spectroscopy will play an important role in the nano-material and
      nano-structure characterization.

PMID- 20038038
TI  - [Study of biological molecules in water by using the resonance raman spectra in
      liquid-core optical fiber].
AB  - Raman spectrum is an important and effective method for the study of biological
      molecules in water. Measuring the Raman spectra for biological molecules in
      water, however, is very difficult because of the small Raman scattering cross
      section and the high electronic excitation energy of water molecules. In the
      present paper, the authors applied both technologies of liquid-core optical fiber
      and the resonance Raman spectra, then the intensity of Raman spectra was enhanced
      to a great extent. In this experiment, we chose the laser wavelength 514.5 of Ar+
      ion laser as excitation laser, because we could obtain the maximal intensity of
      resonance Raman spectra at this wavelength. The experiment results show that, for
      the trace inspecting study of beta-carotene biological molecules in water, the
      concentration in the range of 10(-7)-10(-9) mol x L(-1) can be detected by quartz
      liquid-core optical fiber and the concentration in the range of 10(-9)-10(-10)
      mol x L(-1) by Teflon liquid-core optical fiber. The detecting utmost will be
      further reduced if improving the quality of optical fiber.

PMID- 20038039
TI  - [Raman and FTIR characteristics of otolith of ornamental carp].
AB  - Otolith is a typical natural biomineral as functional deposit existing in
      teleost's ears, which is mainly composed of calcium carbonate and organic matter.
      There is a pair of lapillus, sagitta and asteriscus in fish's inner ear,
      respectively. The authors compare the asteriscus and lapillus in cultured
      ornamental carp using FTIR and Raman. The result shows that the mineral phase in
      lapillus is aragonite, while the mineral phase in asteriscus is vaterite. The
      pure aragonite and vaterite existing respectively in otolith are of importance as
      being used as sample to study aragonite/vaterite biomineralization mechanism.
      Compared with inorganic induced aragonite and vaterite using FTIR and Raman, the
      authors found that the spectra of aragonite in lapillus are between those of
      inorganic induced aragonite and other bio induced aragonite; while the spectra of
      vaterite in asteriscus are similar to those of other bio induced vaterite. It is
      possible that unstable vaterite was stabilized through the organic effects in
      biomineralization process.

PMID- 20038040
TI  - [Effects of cations in chlorine salt solution on O-H stretching Raman spectra of
      water].
AB  - In order to understand the effects of the common cations in geofluids on the
      structure of water, the present paper systematically studied the Raman spectra of
      NaCl-H2O, CaCl2-H2O, MgCl2-H2O, CuCl2-H2O, ZnCl2-H2O and FeCl3-H2O solutions by
      two methods. (1) The frequency shifts of the peak maximum around 3,400 cm(-1) in
      O-H stretching Raman spectra of water reveal the destruction effects of these
      cations on the structure of water: Ca2+ > Mg2+ > Na+, Fe3+ > Zn2+ > Cu2+; (2)
      Comparing the intensities of the shoulder peak around 3,250 cm(-1) in the O-H
      stretching Raman spectra of water: (1) all salts concerned destruct the structure
      of water; (2) with respect to the same chloride, the destruction extent of
      hydrogen-bond increases with concentration increasing; (3) comparing different
      chloride solutions at the same concentration, the destruction effects of catnions
      on the structure of water decrease in the sequences Ca2+ > Mg2+ > Na+ and Fe3+ >
      Zn2+ > Cu2+. (4) A hydrogen bond-affected mechanism combining cation destruction
      with complex compound production is supposed for the first time, and is used to
      explain the effects of the canions on the structure of water: CaCl2 > MgCl2 >
      FeCl3 > NaCl > ZnCl2 > CuCl2.

PMID- 20038041
TI  - [Reproduction features of reflectance spectrum of natural plant flower color].
AB  - Based on the sRGB color space as an important color space of computer display,
      the authors explored color reproduction features in sRGB. In the terms of "color
      clipping" of color space transformation from CIE1931XYZ to sRGB, the color
      reproduction errors in sRGB of 218 reflectance spectra of natural plant flower
      color were examined. Considering the importance of D65 illumination, the
      reproduction features of natural color under D65 were emphasized. It was
      concluded as follows. Firstly, "color clipping" is the key cause of color
      transformation error of the natural plant color when it is transformed from
      CIE1931XYZ to sRGB color space. Secondly, under D65 eight orange and yellow
      reflectance spectra in 218 natural color show clipping in sRGB color space,
      accounting for 3.7% of all samples. Finally, the color reproduction of natural
      plant flower color in sRGB under D65 is the best, while the A illumination is the
      worst.

PMID- 20038042
TI  - [Farmland parcel extraction based on high resolution remote sensing image].
AB  - A new method of farmland parcel extraction from high resolution remote sensing
      image based on wavelet and watershed segmentation was proposed in the present
      paper. First, classification results were used to enhance the contrast of gray
      scale value of typical pixels in the original image using the high resolution
      remote sensing image's spectral information. Second, wavelet transform and
      watershed segmentation were applied to the enhanced image, then improved region
      merger algorithm was used to solve the problem of over-segmentation. Finally,
      inverse wavelet transform was taken to get the reconstructed image, then Canny
      operator was introduced to add the edge information, and the result of farmland
      parcel segmentation was obtained. To validate the proposed approach, experiments
      on Quickbird images were performed, we rapidly extracted the farmland parcel from
      the test image, and the results had a high accuracy. Despite it had a lot to do
      in extracting the small size parcels, on the whole the method this paper proposed
      had a very good robustness. Compared with the traditional methods, it had the
      following advantages: (1) it was an automatic extraction method, did not need too
      much manual intervention, and could extract the large area of farmland parcels
      accurately and effectively. (2) It was a very good solution to the problem of
      over-segmentation by using improved region merger algorithm, and improved the
      accuracy of the extraction. All these indicated that the proposed approach was an
      effective farmland parcel extraction method based on high resolution remote
      sensing image.

PMID- 20038043
TI  - [Study on hyperspectral characteristics of apple florescence canopy].
AB  - The present study aims to systematically analyze the hyperspectral
      characteristics of apple florescence canopy and explore the sensitive spectra to
      provide the theoretical basis for large area apple information extracting and
      remote sensing retrieval for nutrition diagnosis. Based on the 120 hyperspectral
      data of apple florescence canopy acquired with ASD Field Spec 3 portable object
      spectrometer, the effects of different sample numbers on hyperspectral
      characteristics were analyzed. Using variance analysis method, the hyperspectral
      characteristics of apple florescence canopy and the sensitive wave bands were
      obtained. The results showed that with the increase in cumulative sample numbers,
      the hyperspectrum curves of apple florescence became stable and smooth. At the
      550 nm green peak and the 760-1,300 nm reflection plateau, the reflection rate
      reduced with the increase in flowering amount, while in the red valley of 670 nm,
      the reflection rate increased with the increase in flowering amount; At the wave
      bands of 350-500, 600-680 and 760-1,300 nm, the variance analysis results showed
      very significant differences, indicating that they were sensitive wave bands of
      florescence canopy. With the increase in flowering amount, the red-edge position,
      the red-edge slope and red edge area tended to decrease gradually.

PMID- 20038044
TI  - [Research on hyperspectral information parameters of chlorophyll content of rice
      leaf in Cd-polluted soil environment].
AB  - The remote sensing pollution mechanism in Cd-polluted soil is discussed depending
      on the research into the chlorophyll content of Cd-polluted rice leaf in the
      present paper. The response models of remote sensing information parameters,
      which reflected chlorophyll content variety of rice canopy with soil Cd pollution
      degree, were established based on Hyperion satellite data and a great number of
      ground experiment data. To extract sensitive remote sensing parameters for Cd
      pollution, multiple discriminant analysis (MDA) was applied to the reflectivity
      of 447-925 nm in Hyperion data and five remote sensing information parameters,
      including MCARI, NPCI, RVSI, NDVI and Depth671. Experiments indicated that MCARI
      is the most sensitive parameter to the chlorophyll content of Cd-polluted rice,
      whose response coefficient is 0.59. In the extent of 1.0-2.0 mg x kg(-1) of Cd
      pollution concentration in soil, MCARI curve shows a small decline. In the extent
      of 2.0-3.0 mg x kg(-1) of Cd pollution concentration in soil, MCARI curve is
      horizontal. Above 3.0 mg x kg(-1), MCARI shows a significant drop trend and so
      on. The research results showed that the chlorophyll content is a good indicator
      for nutrition situation of plant, capacity of photosynthesis and each
      developmental stage. And the chlorophyll remote sensing parameters in crop have a
      great significance for monitoring heavy metal pollution This study will help
      improve the precision and limitation of statistical methods and provide
      theoretical basis for and technical approach to monitoring soil Cd pollution in
      large area using hyperspectral remote sensing technology. However, the precision
      of pollution model needs to be improved.

PMID- 20038045
TI  - [Three-dimensional hybrid denoising algorithm in derivative domain for
      hyperspectral remote sensing imagery].
AB  - To tackle denosing problems in hyperspectral remote sensing imagery, a three
      dimensional hybrid denoising algorithm in derivative domain was proposed. At
      first, hyperspectral imagery is transformed into spectral derivative domain where
      the subtle noise level can be elevated. And then in derivative domain, a wavelet
      based non-linear threshold denoising method, Bayes-Shrink algorithm, is performed
      in the two-dimensional spacial domain. In the spectral derivative domain,
      considering that the noise variance is different from band to band, the spectrum
      is smoothed using Savitzky-Golay filter instead of wavelet threshold denoising
      method. Finally, the data smoothed in derivative domain are integrated along the
      spectral axis and corrected for the accumulated errors brought by spectral
      integration. The algorithm was tested on airborne visible/infrared imaging
      spectrometer (AVIRIS) data cubes with signal-to-noise ratio (SNR) of 600 : 1.
      Experimental results show that the proposed algorithm can reduce the noise
      efficiently, and the SNR is improved to more than 2 000 : 1.

PMID- 20038046
TI  - Automatically smoothing the spectroscopic data by Cubic B-spline basis functions.
AB  - In the present paper, a new criterion is derived to obtain the optimum fitting
      curve while using Cubic B-spline basis functions to remove the statistical noise
      in the spectroscopic data. In this criterion, firstly, smoothed fitting curves
      using Cubic B-spline basis functions are selected with the increasing knot
      number. Then, the best fitting curves are selected according to the value of the
      minimum residual sum of squares (RSS) of two adjacent fitting curves. In the case
      of more than one best fitting curves, the authors use Reinsch's first condition
      to find a better one. The minimum residual sum of squares (RSS) of fitting curve
      with noisy data is not recommended as the criterion to determine the best fitting
      curve, because this value decreases to zero as the number of selected channels
      increases and the minimum value gives no smoothing effect. Compared with
      Reinsch's method, the derived criterion is simple and enables the smoothing
      conditions to be determined automatically without any initial input parameter.
      With the derived criterion, the satisfactory result was obtained for the
      experimental spectroscopic data to remove the statistical noise using Cubic B
      spline basis functions.

PMID- 20038047
TI  - [Estimation of regional leaf area index by remote sensing inversion of PROSAIL
      canopy spectral model].
AB  - The present paper selected Qing yundian town and Weishanzhuang town in Da Xing
      District, and Gaoling ying town in Shunyi District as test areas, using MODIS
      data and ASTER data in different scales. The feasibility of winter wheat LAI
      inversion by PROSAIL physical model, especially the stability of remote sensing
      data in different scales, was discussed, and the results from experience model
      inversion were compared with that from statistical methods. The values of all
      samples LAI inversion from experience model are close in a region, which means
      experience model is a reflection of general growing trend, ignoring spatial
      heterogeneity of the regional leaf area index. But the value of LAI inversion
      from physical model can be truer in reflecting spatial heterogeneity of the
      regional leaf area index. The value of LAI inversion from physical model is more
      real, compared with experience model. With the method of linear weighing, the
      scale conversion was accomplished, and the LAI inversion results from different
      remote sensing scale data were compared, and were found similar. The result shows
      that in the process of large-scale regional LAI inversion, physical model
      inversion is more valid.

PMID- 20038048
TI  - [Identification and classification of rice leaf blast based on multi-spectral
      imaging sensor].
AB  - Site-specific variable pesticide application is one of the major precision crop
      production management operations. Rice blast is a severe threat for rice
      production. Traditional chemistry methods can do the accurate crop disease
      identification, however they are time-consuming, require being executed by
      professionals and are of high cost. Crop disease identification and
      classification by human sight need special crop protection knowledge, and is low
      efficient. To obtain fast, reliable, accurate rice blast disease information is
      essential for achieving effective site-specific pesticide applications and crop
      management. The present paper describes a multi-spectral leaf blast
      identification and classification image sensor, which uses three channels of crop
      leaf and canopy images. The objective of this work was to develop and evaluate an
      algorithm under simplified lighting conditions for identifying damaged rice
      plants by the leaf blast using digital color images. Based on the results
      obtained from this study, the seed blast identification accuracy can be achieved
      at 95%, and the leaf blast identification accuracy can be achieved at 90% during
      the rice growing season. Thus it can be concluded that multi-spectral camera can
      provide sufficient information to perform reasonable rice leaf blast estimation.

PMID- 20038049
TI  - [Study on combinatorial optimization of spectral principal components using
      successive projections algorithm].
AB  - Successive projections algorithm (SPA) was employed to select the optimal
      combination of principal components (PCs) which were obtained by principal
      component analysis. Short-wave near infrared spectra of milk powder was firstly
      analyzed by PCA, and the optimal combination of obtained first eight PCs was
      determined by SPA. The optimal PC combination of fat content prediction was PC1 ,
      PC2, PC 4, PC5, PC6 and PC7, and the combination for protein content prediction
      was PC1, PC2, PC3, PC4, PC5 and PC8. Least-squares support vector machine models
      inputted by different PC combination were established to predict fat and protein
      content, respectively. Both the fat and protein content prediction results of the
      PC combination selected by SPA were better than those of first four PCs to first
      eight PCs. Rp2, and root mean square errors for prediction and residual
      predictive deviation of prediction results of the PC combination selected by SPA
      were 0.989, 0.1703 and 9.5343, respectively for fat, and 0.9876, 0.1348 and
      8.9274 for protein. The overall results demonstrate that SPA can fast and
      effectively select the optimal PC combination. The selecting process is simple
      and does not need abundant parameter debugging.

PMID- 20038050
TI  - [Spectroscopic study on the interaction of glass matrixes and nanoparticles in
      Tm3+ doped oxyfluoride glass ceramics].
AB  - Fluorescence emission spectra from Tm3+ in crystal phase and glass phase were
      separated under selective excitation of 1D2 level in Tm3+ doped transparent
      oxyfluoride glass ceramics containing LaF3 nanocrystals. Emissions from the
      crystal phase and from the glass phase were detected. The influence of the
      interaction between glass matrix and nanocrystals on the optical characteristics
      of Tm3+ ions in the two different local environments was investigated. The
      results indicate that the increase in nanocrystal size results in a decrease in
      the impact of oxides glass on Tm3+ in the crystal phase, and an enhancement of
      the impact of nanocrystals on Tm3+ in the glass phase. For smaller nanoparticles,
      the emission efficiency of Tm3+ ions in the crystal phase was reduced, and the
      influence of nanocrystals on the ions in the glass phase was reduced too. The
      larger the nanocrystal size, the weaker the influence of oxide glass on the Tm3+
      ions in the crystal phase, and the better performance of fluorescence emission.
      It was also found that the content of SiO2 in glass matrix could affect the
      emission efficiency of Tm3+ in both environments.

PMID- 20038051
TI  - [Application of 1D wavelet analysis in detecting species of harmful algae blooms
      with absorption spectra of phytoplankton].
AB  - In the present study, the feasibility of using wavelet analysis to extract the
      eigen spectra from the absorption spectra of phytoplankton for species detection
      was investigated. Thirteen absorption spectra taken from single species cultures,
      representing four divisions (Dinophyta, Bacillariophyta, Haptophyta, and
      Chlorophyta), six genus (Gymnodinium, Prorocentrum, Skeletonema, Guinardia,
      Phaeocystis, and Prasinophyte) and seven species (Karenia mikimotoi, Karenia
      brevis, Prorocentrum minimum, Skeletonema costatuma, Guinardia delicatula,
      Phaeocystis globosa, and Pyramimonas parkeae), were used. First, the 1D wavelet
      analysis with five levels was applied to the thirteen absorption spectra, so each
      spectrum was decomposed with 5 levels. The 5th level component of low frequency
      corresponds to the background without information for species detection, and 1st
      and 2nd level component of high frequency is the random noise. The other levels
      (3rd to 5th) of high frequency are the useful information, and the sum of levels
      (3rd to 5th) of high frequency was retained as the eigen spectra for species
      detection. Second, the clustering analysis was used to the eigen spectra for
      examining the performance of the wavelet analysis in extracting species
      information. The clustering results were compared with the known species class
      information, and the results show that the 13 absorption spectra are correctly
      classified at the level of division, genus and species. This means that the
      wavelet analysis has good performance in extracting the eigen spectra for species
      detection. However, the above results were obtained with only limited species,
      and the more species data are required to identify the extensive validity of the
      conclusion.

PMID- 20038052
TI  - [Study on the circular dichroism of (S)- and (R)- Wuweizisu C].
AB  - The circular dichroism (CD) is an excellent method for determining the absolute
      stereochemistry of organic compounds. The CD spectra of four biphenyl compounds
      were determined by using CD spectrometer, and two pairs of symmetrical CD spectra
      were obtained. The absolute configuration of biphenyl bond was confirmed by the
      Cotton effect according to the CD rule. The CD spectrum of compound 3 shows a
      negative Cotton effect at 256 nm, and a positive Cotton effect at 220 nm, which
      predicts an S-configuration of biphenyl according to an experimental CD rule.
      Conversely, the CD spectrum of compound 3' displays a positive Cotton effect at
      256 nm, and a negative Cotton effect at 219 nm, which predicts an R-configuration
      of biphenyl. And the regularity of oxazoline-mediated Ullmann reaction was
      obtained, too.

PMID- 20038053
TI  - [Spectral characteristics of normal breast samples in the 350-850 nm wavelength
      range].
AB  - Spectral characteristics of normal female breast samples in the 350-850 nm
      wavelength range were measured using a UV/Vis/NIR spectrophotometer system with
      integrating sphere attachment for measuring the diffuse reflectance and
      transmittance. The optical properties of normal breast tissue in vitro were
      obtained by the inverse adding doubling method. And then the optical penetration
      depths in this spectral range were analyzed based on the principle of tissue
      optics. The results show that the reduced scattering coefficient of normal female
      breast tissue is significantly higher than the absorption coefficient in the 350
      850 nm wavelength range. The reduced scattering coefficient decreases with the
      wavelength increment. It reaches maximum at shorter wavelengths with a decrease
      at longer wavelengths and ranges from 9.731 mm(-1) at 350 nm to 1.476 mm(-1) at
      850 nm. The absorption coefficient of normal breast tissue is about from 0.798
      mm(-1) at 350 nm to 0.102 mm(-1) at 850 nm. The maximal and minimal values are at
      350 nm and 850 nm respectively. An absorption peak for the normal breast tissue
      is at 410 nm of wavelength with the value of 0.506 mm(-1), which belongs to
      hemoglobin. The absorption coefficient remains relatively constant when the
      wavelength is longer than 600 nm. The optical penetration depth increases with
      the wavelength increment and ranges about from 0.199 mm at 350 nm to 1.439 mm at
      850 nm. Deep penetration depth noted in normal breast samples, especially at
      longer wavelengths, reflects the weak absorption and reduced scattering at these
      wavelengths. The calculated optical parameters of normal breast samples by the
      inverse adding doubling method agree well with the Monte Carlo simulations. This
      study may be useful for breast optical biopsy or the optical diagnosis of breast
      diseases.

PMID- 20038054
TI  - [Spectroscopy study of methyl parathion molecularly imprinted polymers].
AB  - Three molecularly imprinted polymers were synthesized with different functional
      monomers respectively, using methyl parathion as the template. These monomers are
      methacrylic acid, acrylamide and 4-vinylpyridine. According to the UV spectrum
      study the interaction between methyl parathion and 4-vinylpyridine was stronger
      than that of the others. Comparably, the infrared spectrum study showed the same
      results which indicated that 4-vinylpyridine could associate with the template at
      two different kinds of binding sites, the P-O-C and the -NO2 site, and is most
      likely to form steady covalent bonds with methyl parathion, while the other two
      monomers could only associate with the template at the P-O-C site. Furthermore,
      the infrared spectra of the synthesized polymers confirmed the existence of the
      functional groups in each kind of polymer, which might interact with the
      template.

PMID- 20038055
TI  - [Analysis of NIR characteristic wavelengths for apple flesh firmness based on GA
      and iPLS].
AB  - In the present study, the fruit flesh firmness of apple was analyzed by near
      infrared (NIR) spectroscopy using an FT-NIR spectrometer. The sensitive spectral
      regions that provide the lowest prediction error were analyzed by different well
      known variable selection methods, including dynamic backward interval partial
      least-squares (dynamic biPLS), sequential application of backward interval
      partial least-squares and genetic algorithm(dynamic biPLS & GA-PLS), and
      iterative genetic algorithm partial least-squares (iterative GA-PLS). Iterative
      GA-PLS, dynamic biPLS & GA-PLS led to a distinct reduction in the number of
      spectral data points with better predictive quality. Furthermore, the majority of
      selected wavelengths were content with the characteristic of the sorption bands
      of fruit flesh firmness. Pectin constituents, complex non-starch polysaccharides,
      which are related to texture change in apple, play an important role in their
      harvest maturity, ripening and storage. Comparing NIR characteristic wavelengths
      of apple flesh firmness and typical absorption bands for pectin, it was found
      that characteristic wavelengths of apple flesh firmness were consistent with the
      pectins relevant spectral regions. Therefore, the NIR characteristic wavelengths
      of apple firmness based on GA and iPLS reflected the chemical component of apple
      and the results were reasonable.

PMID- 20038056
TI  - [Structure and vibrational spectroscopy of ginsenoside Re: density functional
      theory study].
AB  - Density functional theory was used to optimize the geometry structure of two
      isomers of ginsenoside, Re, 20-(R)-R and 20-(S)-Re. The ginsenoside Re is an
      active constituent in ginseng. The calculated results show that there is an
      obvious difference in space structure between 20-(R)-R and 20-(S)-Re. The main
      reason for that can be the difference in the space orientation of the four
      constituents in the 20th carbon (chiral), which leads to the different stacking
      mode and causes the difference in vibrational spectra in the two isomers. The
      experimental IR and Raman spectra were assigned according to the calculated
      frequency, theoretical IR intensity and Raman active. The calculated vibrational
      peaks at 1,541, 1,456 and 1,424 cm(-1) can be used to distinguish the two
      isomers. The result shows a good agreement between the calculated and the
      experimental Raman spectra. The vibrational spectra can be used to identify the
      active constituent in ginseng.

PMID- 20038057
TI  - [Increasing SNR of dynamic spectrum method using harmonic waves].
AB  - The sources of noise in dynamic spectrum (DS) method and their corresponding
      frequency characteristic were analyzed in order to improve the signal to noise
      ratio (SNR) of DS method. The processes of DS data in frequency domain were
      reviewed by means of energy, then the harmonic waves of DS data were taken into
      account in the DS signal and some experiments were done to test whether the
      modified method works well. In addition, corresponding experiments were carried
      out to seek the relationship between the SNR and the number of harmonic waves,
      and to determine how many harmonic waves should be involved in order to get the
      best SNR in DS method. Results showed when harmonic waves were used in the method
      properly, the modified method can distinguish DS more precisely. And it was also
      showed that as the number of harmonic waves increased, the correlation
      coefficient of DS data from different volunteers became smaller at first and then
      bigger later, while the correlation coefficient of DS data from different
      sampling site of the same volunteer kept increasing all the time. When the number
      of harmonic waves was set to 5, the correlation coefficient of DS data from
      different volunteers goes from 0.73752 to 0.73676, while the one from the same
      volunteer goes from 0.99416 to 0.99533, which means the modified method can
      reflect the information about blood component more precisely than the old ones,
      and thus the SNR of DS reaches the highest.

PMID- 20038058
TI  - [Spectroscopy and thermostability of series rare-earth complexes with 3
      nitrophthalic acid].
AB  - A series of rare-earth compound RE2L2 (HL)2 (H2O)6 x 2H2O (RE=La, Nd, Eu, Tb, Er,
      Y) containing 3-nitrophthalic acid (H2L) ligand were synthesized from ethanol
      water solution, and characterized and investigated by the element analysis,
      infrared and ultraviolet absorption spectra and different thermal
      thermogravimetric analysis. The results of the spectroscopic analysis were
      conformed to the crystal structures determined by X-ray diffraction, showing that
      the carboxylate (-COO-) and carboxyl (-COOH) groups of the ligand link to the
      rare-earth ions by bridging and terminal mode respectively. Two rare-earth ions
      were linked by two di-deprotonated ligand L(2-) in bridging-chelating mode to
      form a dinuclear structure, and coordinated by the other two mono-deprotonated
      ligands HL-in terminal chelating mode using their carboxylate (-COO-) and
      carboxyl (-COOH) group together, respectively. The IR spectra shows the existence
      of the carboxylate (-COO-) and carboxyl (-COOH) group and the hydrogen bond
      interactions between the carboxyl (-COOH) group and crystal water. The DTA-TGA
      data were consistent with the composition of compounds, exhibiting an endothermic
      peak of the loss of the crystal and coordinated waters at about 150 degrees C and
      two exothermic peaks of the oxidation and decomposition of ligands in the rang of
      about 340 to 460 degrees C.

PMID- 20038059
TI  - [Preparation and optical properties of fluorescent nanofiber containing europium
      complex].
AB  - Through electrospinning technique, the lanthanide complex with good luminescent
      property, Eu(DBM)3 x H2O and Eu(DBM)4 x CPC, were incorporated into water soluble
      polymer PVP, and the polymer nanofibers with red characteristic fluorescent light
      from europium ion were obtained. The microstructure of the rare earth complexes
      and polymer nanofibers product was studied by scanning electron microscopy and
      transmission electron microscopy, and the result indicated that when the rare
      earth complexes were compounded into the polymer nanofibers, it's microstructure
      changed due to its good compatibility with PVP ethanol solution, and the polymer
      nanofibers with one dimension were of 50-100 nm relatively uniform line shape
      structure. In addition, the fluorescence excitation and emission spectra and
      fluorescence lifetime of the rare earth complexes and polymer nanofibers product
      were studied. Photoluminescence measurements indicate that the lanthanide
      complexes show superior emission lines, higher intensities and longer fluorescent
      lifetime in the polymer nanofibers than in the corresponding pure complex
      powders, which is due to the composite nanofibers providing a relatively stable
      environment for lanthanide complexes.

PMID- 20038060
TI  - [Fluorescence study on the interactions between G3.0 PAMAM dendrimers and bovine
      serum albumin].
AB  - The interaction between amine terminated G3.0 PAMAM dendrimers and bovine serum
      albumin (BSA) under physiological condition was studied by fluorescence
      spectroscopy. Our experiments demonstrated that the fluorescence intensity of BSA
      decreased after the addition of G3.0 PAMAM dendrimers and the quenching mechanism
      was suggested as static quenching according to the Stern-Volmer equation The
      binding constant of G3.0 PAMAM dendrimers with BSA was calculated to be 1.067 +/-
      0.025 L x mmol(-1). At the same time, synchronous fluorescence and red edge
      excitation shift (REES) were adopted to review the conformational changes of BSA
      influenced by G3.0 PAMAM dendrimers, which provides important significance for
      clinical medication And the results indicated that G3.0 PAMAM dendrimers can
      change the conformation of BSA. Furthermore, this article also examined the
      influence of pH and ionic strength on the interactions, from which we can
      conclude that electrostatic interaction played major roles in the binding
      process. In conclusion, the fluorescence method is a highly sensitive and
      convenient way to study intermolecular interaction. Further investigation in this
      field will provide more important information for understanding the
      pharmacological effects and toxicities of drugs in human body.

PMID- 20038061
TI  - [Value of auto-fluorescence spectrum combined with tumor markers in diagnosis of
      lung cancer].
AB  - To improve the diagnostic efficiency of cancer, serum fluorescence spectrum
      combined with tumor marker groups was proved more powerful, especially when used
      with mathematical evaluation model, that is, artificial neural network (ANN)
      modeling. ANN modeling is very suitable for the discrimination of lung cancer.
      ANN has evident superiority in solving nonlinear, multi-parameter and uncertain
      complicated problems. In the present paper, serum fluorescence spectrum was
      applied to study the difference among normal, benign and malignant groups and
      develop the relevant method of determination. On the other hand, combined with
      tumor markers, CEA, NSE, SCC-Ag, CYFRA21-1 and p16 methylation, artificial neural
      network and Fisher linear discriminatory analysis were used to develop the
      prediction models of diagnosis of lung cancer, and compared by ROC. It was shown
      that the result of the fluorescence spectrum combined with tumor markers based on
      ANN model is superior to that of the fluorescence spectrum ANN model. The
      performance of ANN model is superior to that of Fisher linear discriminatory
      analysis.

PMID- 20038062
TI  - [Study on the designed self-assembling peptide as potential drug carrier by
      fluorescence spectra].
AB  - Amphiphilic peptide is becoming attractive as a potential drug carrier to improve
      the dissolvability of hydrophobic drugs in aqueous system thus facilitating the
      drug undertaken by target cells. Here, we reported the ability of a novel
      designed self-assembling peptide RGA16 (Ac-RADAGAGARADAGAGS-NH2) in drug
      encapsulation and transfer into lipid vesicles. Pyrene was used as a model
      hydrophobic drug, and egg phosphatidylcholine (EPC) vesicles were used as plasma
      membranes mimic. It was found that the pyrene and peptide formed complex in water
      with mechanical stirring, and the time duration over which the complex formed was
      about 5 days. Initial evidence of the association between RGA16 and pyrene was
      the observation of a clouding phenomenon. Further investigation on the
      interaction between RGA16 and pyrene was carried out using fluorescence spectra
      and scanning electron microscopy (SEM). SEM micrographs showed that pyrene
      crystals and peptide were absorbed by each other and the size of the pyrene
      peptide complexes was larger than 10 microm, which provided an evidence for the
      encapsulation of pyrene molecule by the amphiphilic peptide. The steady
      fluorescence excitation profiles showed that the pyrene was presented in the
      crystalline form when stabilized by RGA16 and molecularly migrated from its
      peptide coating into the membrane bilayers of EPC vesicles when the suspension
      was mixed with EPC vesicles. The release behavior of pyrene into EPC vesicles was
      investigated by steady-fluorescence emission spectra, and a calibration curve for
      the amount of pyrene released into the EPC vesicles at a given time was used to
      determine the final concentration of pyrene released into lipid vesicles from
      peptide-pyrene complex. It was found that the pyrene concentration in EPC
      vesicles was displayed as a function of time. The data presented in the present
      work suggested that the novel designed amphiphilic peptide could stabilize the
      hydropholic drug in aqueous solution and deliver it into the membrane bilayers of
      EPC vesicles.

PMID- 20038063
TI  - [Study on interaction of caffeine with myoglobin by fluorescence spectroscopy].
AB  - The interaction of caffein and myoglobin was investigated by fluorescence
      spectroscopy and synchronous fluorescence spectroscopy. The intrinsic
      fluorescence of myoglobin was significantly quenched by caffein under the
      physiological condition (pH 7.4). The results indicated that caffeine was capable
      of binding with myoglobin to form a 1:1 complex and the quenching mechanism of
      myoglobin affected by caffeine was shown to be a static quenching procedure by
      calculating quenching constant, binding sites and binding constant. According to
      the thermodynamic parameters, the main binding force of the interaction is
      electrostatic force and hydrophobic force. The change in the micro-circumstance
      of aminos of myoglobin was analyzed by synchronous fluorescence spectrometry. The
      result indicated that caffeine can change the conformation of the protein,
      leading to the change in the micro-environment of tryptophane and tyrosine
      residues from hydrophobic environment to hydrophilic environment to different
      extent.

PMID- 20038064
TI  - [Synthesis, characterization and fluorescence of Zn3 (NCS)6 (L1)6 (NO3)2 and
      Ni3(NCS)6(L2)6(NO3)2].
AB  - The complexes of Zn2+, Ni2+ with 4-amino-3,5-dimethyl-1,2,4-triazole and 4-amino
      1,2,4-triazole were synthesized in water, respectively. By elemental analysis,
      coordination titration and molar conductivities studies, the compositions of the
      complexes were suggested as Zn3 (NCS)6 (L1)6 (NO3)2 and Ni3 (NCS)6 (L2)6 (NO3)2
      respectively. The ligands and coordination compounds were studied by means of IR
      spectra, UV and fluorescence excitation and emission spectra. The IR spectra
      studies indicate that triazolate was bonded with RE (II) through nitrogen atoms
      in the heterocyclic ring. The fluorescence spectra showed that the fluorescence
      emission intensity of Ni3 (NCS)6 (L2)6 (NO3)2 was stronger than that of Zn3
      (NCS)6 (L1)6 (NO3)2.

PMID- 20038065
TI  - [Simultaneous determination of PAHs in food by low-temperature constant-energy
      synchronous fluorescence spectrometry].
AB  - The authors developed a rapid analytical method that could determine the PAHs in
      food samples simultaneously by the coupled approach of Shpol' skii spectroscopy
      and constant-energy synchronous fluorescence scanning technique. Low-fat food
      samples, which were just extracted with octane and high-fat food samples pre
      processed with saponification and extracting, could be analyzed immediately. The
      recoveries ranged from 80.2% to 98.9% and the correlation coefficients of the
      linearity were higher than 0.993 8. This method was selective, simple, rapid and
      inexpensive.

PMID- 20038066
TI  - [Synthesis and spectrum of novel pyrazoline fluorescent compounds].
AB  - Pyrazoline derivatives have been used widely in dyeing industry as fluorescent
      whitening agents due to their excellent capability. According to Schellhammer
      theory of the relation between chemical structure and fluorescent quality, six
      new fluorescent compounds were designed and synthesized which contained the
      benzothiazole group in the 1-pyrazoline, the indole group in the 3-pyrazoline and
      the derivatives of phenyl in the 5-pyrazoline. The structure of target compounds
      was confirmed by IR, 1H NMR, MS and elementary analysis. The fluorescence spectra
      showed that these compounds had good fluorescence. They could absorb ultraviolet
      light at near 353 nm. The fluorescence maximum emission wavelengths were about
      430-443 nm. It was a kind of promising fluorescence compounds. The largest
      fluorescence emission wavelength and the fluorescence intensity were related to
      the substituted group of the compounds. When the 6-Br group was introduced into
      benzothiazole, the fluorescence emission wavelength exhibited a blue shift, and
      the fluorescence intensity increased. Otherwise, the CH3 group was introduced
      into benzothiazole, the fluorescence emission wavelength red-shift occurred, and
      the intensity was lower. The fluorescence quantum yield of the compounds was
      little affected by the substituted group and polarity of the solvent The relative
      fluorescence intensity and fluorescence quantum yield were not directly related.

PMID- 20038067
TI  - [UV-Vis studies on the course of reaction of Au/Ag alloy colloid with hydrogen
      tetrachloroaurate(III) hydrate].
AB  - Using citrate as protector, Au-Ag alloy nanoparticles with different molar ratios
      were prepared with hydrazine as the reducer. One plasmon band between
      monometallic Ag and Au was observed in their UV-Vis spectra. And the peak of
      alloy shifted linearly with the ratio of Au changing in the alloy. By UV-Vis
      spectra, the course of reaction of the alloy colloid with HAuCl4 was studied. The
      result shows that the UV-Vis spectra of the alloy colloid changed regularly with
      the adding volume of HAuCl4 increasing. And there is a linear interval in it with
      the change in the calculated ratio of Au. With the former studies, the course can
      be attributed to the dealloy of Au/Ag alloy.

PMID- 20038068
TI  - [Kinetic study on inhibition effects of dansyl-L-phenylalanine and L
      phenylalanine on calf intestinal alkaline phosphatase].
AB  - To evaluate the inhibition effect of dansyl-L-phenylalanine on calf intestinal
      alkaline phosphatase (CIAP), UV-Vis spectrophotometric method was employed. It
      was found that dansyl-L-phenylalanine can selectively inhibit CIAP. The kinetic
      inhibition processes of dansyl-L-phenylalanine and L-phenylalanine were
      comparatively studied. The authors' finding elucidates that at the optimized
      alkaline pH of alkaline phosphatase (pH 10.4) and 37 degrees C, dansyl-L
      phenylalanine can inhibit alkaline phosphatase activity of CIAP efficiently and
      specifically, similar as L-phenylalanine. Both inhibition types were
      uncompetitive inhibition resulting from the double reciprocal curve fitting of
      upsilon versus substrate concentrations, and the inhibition constants Ki of both
      inhibitors were determined to be 2.3 and 1.1 mmol L(-1) respectively, both of
      which were at millimolar level. The investigation of the inhibition effect of
      dansyl modified L-phenylalanine on calf intestinal alkaline phosphatase not only
      helped get insight into the detailed inhibition mechanism of L-phenylalanine on
      tissue specific alkaline phosphatase, such as in the case of intestinal alkaline
      phosphatase, but also provided the possibility to employ fluorescence
      spectroscopy by labeling the specific inhibitors of alkaline phosphatase with
      chromophoric groups.

PMID- 20038069
TI  - [BPNN simulation of photocatalytic degradation of reactive scarlet BES by UV-Vis
      spectrophotometer].
AB  - The use of chemometric techniques and multivariate experimental designs for the
      photocatalytic reaction of reactive scarlet BES in aqueous solution under
      ultraviolet light irradiation is described. The efficiency of photocatalytic
      degradation was evaluated by the analysis of the parameter of decoloration
      efficiency determined by UV absorption at 540 nm using a UV-Vis spectrophotometer
      in different conditions. Five factors, such as the amount of titanium oxide
      ([TiO2]), the concentrations of reactive scarlet BES (c(0)), irradiation time
      (t), the pH value (pH) and temperature (T), were studied. [TiO2]. c(0), t and pH
      selected on the basis of the results of variance analysis by Plackett-Burman
      design were used as independent variables. Training sets and test sets of back
      propagation neural network (BPNN) were formed by Box-Behnken design and uniform
      design U10 (10 x 5(2) x 2) respectively. The process of photocatalytic
      degradation of the target object was simulated by the BPNN model. The correlation
      coefficient (r) of the calculation results for training set and test set by BPNN
      is 0.996 4 and 0.963 6 respectively, and the mean relative errors between the
      predictive value and experimental value of decoloration efficiency are 6.14 and
      7.76, respectively. The modeled BPNN was applied to analyze the influence of four
      factors on decoloration efficiency. The results showed that the initial
      conditions of c(0) being lower, pH 5.0 and appropriate amount of [TiO2]
      contribute to improving the decoloration efficiency of reactive scarlet BES.
      Under the condition of c(0) = 40 mg x L(-1), the optimized experimental condition
      of the system was obtained: [TiO2] = 1.20 g x L(-1) and pH 5.0. Under the
      optimized experimental condition, the experimental value of decoloration
      efficiency is 98.20% when irradiation time is 35 minutes and the predictive value
      of decoloration efficiency is 99.16% under the same condition. The relative error
      of decoloration efficiency between the predictive value and experimental value is
      only -0.96%. The experimental value is very close to the model predicted value.

PMID- 20038070
TI  - [Effect of octadecyl amine (ODA) on the complex titration of magnesium and
      calcium ions studied with UV-visible spectrophotometry].
AB  - The effect of flotation agent octadecyl amine (ODA) on the complex titration of
      both magnesium and calcium ions was studied with two groups of comparative
      experiments: (1) Before titration, the suspension was not filtered. In this case,
      ODA had a great effect on the complex titration of both magnesium and calcium
      ions. The titration end-point of magnesium ions was difficult to be determined.
      Although the titration end-point of calcium ions could be determined, there was
      an obvious experimental error compared with the blank solution without ODA. These
      results were confirmed by the UV-Visible spectrum analyses of the related
      solutions. (2) Before titration, the suspension was filtered. In this case, the
      influence of ODA on the complex titration of both magnesium and calcium ions
      could be removed. UV-Visible spectrum studies showed that, in this case, both the
      spectra and time scanning curves of the tested solutions were similar to those of
      the blank solutions.

PMID- 20038071
TI  - [Simultaneous determination of platinum (IV) and palladium (II) using
      spectrophotometry method].
AB  - The N-(m-methylphenyl)-N'-(sodium p-aminobenzenesulfonate)-thiourea (MMPT) was
      good reagent of water solubility. In the medium of an HAc-NaAc buffer solution
      and hexadecyltrimethylammonium bromide (CTMAB), MMPT can react with platinum (IV)
      and palladium (II) to form green and brown soluble complex. The maximum
      absorbance of the complex was at lambdaPt(max) = 754.4 nm and lambdaPD(max) =
      304.6 nm. Beer's law was obeyed with the concentration in the range of 0-32.0
      microg Pt(IV)/25 mL and 0-25.0 microg Pd(II)/25 mL for platinum (IV) and
      palladium(II) respectively. The correlated coefficient was r754.4 = 0.999 5 for
      platinum (IV); and r304.6 = 0.999 9 for palladium (II). Their molar absorption
      coefficients were epsilonPT(754.4 = 8.6 x 10(4) L x mol(-1) x cm(-1) and
      epsilonPd(304.6) = 7.4 x 10(4) L x mol(-1) x cm(-1) respectively. The contents of
      platinum (IV) and palladium (II) were converted by determination of the
      absorbency of mix solution of platinum (IV) and palladium (II) at 754.4 and 304.6
      nm. Only Cu2+ and Co2+ interfered with the determination of palladium (II) among
      50 coexistent ions, so the selectivity was good. It can be used for the
      determination of content of synthesis samples. The relative standard deviation
      (RSD) was less than 2.0%, and the recovery (%) was in the range of 96%-104%. The
      results are satisfactory. Because the reagent reacts with platinum (IV) and
      palladium (II) to form water soluble complex and does not require pre-separation
      for simultaneous determination of platinum (IV) and palladium (II), the method is
      easy to operate, rapid and environment-friendly.

PMID- 20038072
TI  - [The application of inductively coupled plasma atomic emission spectrometry/mass
      spectrometry to the analysis of advanced ceramic materials].
AB  - Advanced ceramics have been applied to various important fields such as
      information science, aeronautics and astronautics, and life sciences. However,
      the optics and electric properties of ceramics are significantly affected by the
      micro and trace impurities existing in the material even at very low
      concentration level. Thus, the accurate determination of impurities is important
      for materials preparation and performance. Methodology of the analysis of
      advanced ceramic materials using ICP-AES/MS was reviewed in the present paper for
      the past decade. Various techniques of sample introduction, especially advances
      in the authors' recent work, are described in detail. The developing trend is
      also presented. Sixty references are cited.

PMID- 20038073
TI  - [Progress in the method of laser ablation solid sample introduction to
      inductively coupled plasma source].
AB  - On the basis of consulting the home and abroad literatures in recent years, the
      research progress in the method of laser ablation solid sampling to the
      inductively coupled plasma source and its application in the analysis of material
      compositions are described. The present paper emphatically reviewed the influence
      of the laser-beam properties (output wavelength, pulse duration, repetition
      frequency, energy density) and atmosphere gases (helium and argon) on the sample
      ablation process, and discussed the functions of the laser ablation chamber,
      aerosol transmission pipelines, and sample introduction devices improved in the
      process of the evaporated material transferring to the inductively coupled plasma
      source. Getting small uniform aerosol particles and transporting the ablated
      materials to the inductively coupled plasma source efficiently and steadily are
      the key points to make laser ablation solid sampling technique more perfect, and
      the elements fractionation and evaporation deposition are important influence
      factors for the analysis performance. As a practical example, the application of
      laser ablation solid sampling inductively coupled plasma atomic emission
      spectrometry/mass spectrometry in the analysis of metal, glass, organic
      substance, and other samples was also discussed. The accuracy, precision,
      detection limits, and sensitivity of the analysis method were briefly reviewed.

PMID- 20038074
TI  - [Determination of contents of many kinds of metal elements in Phellodendron by
      ICP-AES].
AB  - Dry and wet methods were used to digest Phellodendron grown in Jinxiu Dayaoshan
      of Guangxi with a high-pressure jar and to prepare the samples. The contents of
      microelements Cu, Fe, Zn, Mn and Ni and macroelements K, Ca, Mg, Sr and Na in
      Phellodendron were determined by using ICP-AES. Meanwhile, the optimal digestion
      conditions were found: 7 mL of HNO3 +HClO4 +H2O2 (volume ratio 5 : 1 : 1) for 4
      h. The work condition and the optical wavelength were selected. The RSD was found
      to be less than 5% and the recovery rates of all elements were within the range
      of 89.4%-113.1%. The determined results agree with the analytical demand, and
      also indicate that Phellodendron contains high contents of Cu, Fe, Zn and Mn
      microelements. It is important to assess the medicinal value and understand
      pharmacological action of Phellodendron by the determination of microelements in
      the Chinese medicine with ICP-AES.

PMID- 20038075
TI  - [Determination of trace metal elements in Zanthoxylum nitidum by ICP-AES].
AB  - The contents of twenty microelements were determined in the root, stem and leaf
      of traditional Chinese herbs, Zanthoxylum nitidum by ICP-AES (inductively coupled
      plasma-atomic emission spectrometry) analytical technology. For such method,
      their recovery ratio obtained by standard addition method ranged between 89% and
      107.5%, and most of RSDs were lower than 4%, with good correction and precision.
      The analytical results show that there exist different contents from the
      different parts of the plant. There are most rich elements such as Mg, Na, K, and
      Ca in its three parts, while Mn, Zn, Fe, Cu, Co, Sr and some toxic elements Cd,
      Cr, Pb and Bi were also detected; four elements, Se, V, Mo and Hg, were not
      detected in all parts. There exist many kinds of metal elements benefiting human
      being health, which may provide useful information for the usage of the herbs and
      for the study of the relationship between the elements in Chinese traditional
      medicine and its bioactivities.

PMID- 20038076
TI  - [Simultaneous determination of multi-organotin compounds in seawater by liquid
      liquid extraction-high performance liquid chromatography-inductively coupled
      plasma mass spectrometry].
AB  - The hyphenated technique of high performance liquid chromatography coupled with
      inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was applied to the
      simultaneous determination of five organotin compounds (trimethyltin, dibutyltin,
      tributyltin, diphenyltin and triphenyltin) in seawater samples. Agilent TC-C18
      column was used for the separation, the mobile phase of HPLC was CH3CN : H2O :
      CH3COOH = 65 : 23 : 12 (phi3), 0.05% TEA, and pH value was adjusted to 3.0 by
      diluent ammonia. The flow rate was 0.6 mL x min(-1). Five mixed organotin
      compounds in a mix standard solution from 100 to 0.5 microg x L(-1) were applied
      for the method assessment. The experimental results indicate that the correlation
      coefficient of calibration curves (R2) for each organotin compound was over 0.998
      and the detection limits of the five organotin compounds were lower than 3 ng x
      L(-1). Different mixed organic solvents including dichloromethane or toluene were
      used for extraction of organotin and the extraction condition of organotin from
      seawater was optimized. The 100 mL seawater acidized by hydrochloric acid was
      extracted by 10 mL carbon dichloride (CH2 Cl2) with 2% tropolone for 10 min
      twice. Extracted organic solvents were mixed and blown to one drop by nitrogen
      with the rate of 1.7 mL x min(-1), then 1 mL acetonitrile was added to the drop
      for redissolving the organotin compounds. Finally, the mixed redissolution was
      filtered by 0.22 microm organic filter membrane before analysis. It was found
      that the only organotin compound in seawater was triphenyltin (TPHT) and the
      content was 53.2 ng x L(-1). The recoveries test from the standard addition for
      diphenyltin (DPHT), dibutyltin (DBT), tributyltin (TBT) and triphenyltin (TPHT)
      were over 80%. However, the recovery for trimethyltin (TMT) was relatively low
      and the value was 50%. The reason might be attributed to the decomposition or
      adsorption of those compounds during the extraction procedure. Further study on
      this subject is in progress.

PMID- 20038077
TI  - [Research on discrimination method of vinegar varieties and brands based on the
      content of inorganic elements].
AB  - Classification of brands and quality of food products is a very active area with
      the application of chemometric classification procedures. The content of
      inorganic elements such as Mg, K, Pb, Zn, Fe, Mn, Ca and Cu in 32 vinegar samples
      was determined by atomic absorption spectrophotometer. The similarity of Chencu
      and Baicu as well as different brands of vinegar samples of the same kind was
      calculated by vector similarity analysis. The characteristic discrimination of
      vinegar samples of four brands from Beijing, Jiangxi, Jiangsu and Shanxi was
      accomplished through cluster analysis and principal component analysis, and the
      classification of different kinds of vinegar samples (Chencu and Baicu) was
      performed as well. Vinegar samples were divided into two main groups by cluster
      analysis and principal component analysis. Each main group was discriminated
      according to different brands. The contents of inorganic elements in vinegar were
      good chemical descriptors for differentiation of their kinds and brands.

PMID- 20038078
TI  - [Determination of trace free copper and zinc in serum samples by graphite furnace
      atomic absorption spectrometry after two-step precipitation of protein].
AB  - A method was developed for the determination of trace free copper and zinc in
      serum sample by GFAAS after two-step precipitation. The serum and ethanol were
      mixed with volume ratio of 1 : 2. The mixture was subsequently denatured at 70
      degrees C and centrifuged to precipitate proteins. The determination, limit of
      copper (3sigma) was 1.2 microg x L(-1) and the recovery was 92.3% - 104%, and the
      determination. Limit of zinc(3sigma) was 0.098 microg x L(-1) and the recovery
      was 90%-107%. This two-step precipitation method can be used to determine non
      protein-bound copper in tumor patients and healthy people.

PMID- 20038079
TI  - [Spectral analysis of some brass coins excavsted from Ezhou of Hubei province].
AB  - XRD and XRF were used to identify several brass coins of Qing dynasty collected
      in the Ezhou Museum and excavated from Ezhou of Hubei province. The reality of
      the coins contains 36.53%-37.75% of Zn, 54.12%-59.04% of Cu and 3.51%-7.56% of
      Pb, and the ration of the alloy is steady and scientific, indicating that the
      technic of the alloy of brass was quite perfect in the mid to late of Qing
      dynasty. Zn3Cu2 (OH)6 (CO3)2 was found in the corrosion for the first time, and
      CuO, ZnO, Fe2O3 and CuCl were found too. The high content of Cl-, around the
      local condition (including the polluted environment), may be the main reason for
      those brass coins to be eroded seriously. These findings provide some reference
      for collecting and protecting coins.

PMID- 20038080
TI  - [Preparation, characterization and property of bamboo-like alpha-Fe2 O3
      nanobars].
AB  - Firstly, hydroxide iron precursor was prepared by the co-precipitation method
      through using nitric iron as the source of iron, ammonia as precipitants, and
      poly-glycol as dispersant. Secondly, the precursor was calcined at 450 degrees C
      for 2 h under the protection of nitrogen. Finally, the images and structures of
      resultant powders were investigated by transmission electron microscopes (TEM), X
      ray diffraction (XRD), Raman spectrum and the near-edge X-ray absorption fine
      structure (NEXAFS), respectively, and the magnetic property of resultant powders
      was measured by a vibrating sample magnetometer (VSM HH-50). The experimental
      results of TEM show that the products are composed of Fe2 O3 nano-particles with
      sizes in the range of 50-100 nm and bamboo-like Fe2 O3 nanobars about 10 nm in
      diameter. The experimental results of XRD and spectrum illuminate that the
      structures of products are alpha-Fe2 O3. Moreover, magnetic properties
      measurement reveals that the products exhibit typical magnetic hysteresis loops
      of ferromagnetism materials, and their saturation magnetization and coercive
      force are approximately 64.65 emu x g(-1) and 15.13 Oe, respectively.

PMID- 20038081
TI  - [Development of chlorophyll concentration nondestructive measurement instrument
      based on spectral analysis technology].
AB  - A portable nondestructive measuring instrument for plant chlorophyll was
      developed, which can perform real-time, quick and nondestructive measurement of
      chlorophyll. The instrument is mainly composed of four parts, including leaves
      clamp, driving circuit of light source, photoelectric detection and signal
      conditioning circuit and micro-control system. A new scheme of light source
      driving was proposed, which can not only achieve constant current, but also
      control the current by digital signal. The driving current can be changed
      depending on different light source and measurement situation by actual
      operation, which resolves the matching problem of output intensity of light
      source and input range of photoelectric detector. In addition, an integrative
      leaves clamp was designed, which simplified the optical structure, enhanced the
      stability of apparatus, decreased the loss of incident light and improved the
      signal-to-noise ratio and precision. The photoelectric detection and signal
      conditioning circuit achieve the conversion between optical signal and electrical
      signal, and make the electrical signal meet the requirement of AD conversion, and
      the photo detector is S1133-14 of Hamamatsu Company, with a high detection
      precision. The micro-control system mainly achieves control function, dealing
      with data, data storage and so on. As the most important component,
      microprocessor MSP430F149 of TI Company has many advantages, such as high
      processing speed, low power, high stability and so on. And it has an in-built 12
      bit AD converter, so the data-acquisition circuit is simpler. MSP430F149 is
      suitable for portable instrument. In the calibration experiment of the
      instrument, the standard value was measured by chlorophyll meter SPAD-502,
      multiple linear calibration models were built, and the instrument performance was
      evaluated. The correlation coefficient between chlorophyll prediction value and
      standard value is 0.97, and the root mean square error of prediction is about 1.3
      SPAD. In the evaluation experiment of the instrument repeatability, the root mean
      square error is 0.1 SPAD. Results of the calibration experiment show that the
      instrument has high measuring precision and high stability.

PMID- 20038082
TI  - Hospitals behaving badly.

PMID- 20038083
TI  - Clinical practice corner: health information technology.

PMID- 20038085
TI  - Affinity-trap polyacrylamide gel electrophoresis: a novel method of capturing
      specific proteins by electro-transfer.
AB  - A method for the affinity capture of specific proteins from a complex mixture
      using a polyacrylamide gel technique is described. The approach is based on the
      orthogonal electro-transfer of proteins separated by ordinary polyacrylamide gel
      electrophoresis (PAGE) to a ligand-coupled polyacrylamide gel (Li-PAG), which is
      placed under the PAGE gel. Upon electro-transfer, the proteins orthogonally
      migrate from the PAGE into the Li-PAG, based on the net charge. During migration
      to the Li-PAG, proteins that specifically interact with a ligand can be
      transiently trapped in the Li-PAG, while those that do not interact with a ligand
      pass through it. This method permits the separation of the proteins that can
      specifically interact with a ligand, even when present in a complex mixture. The
      method is demonstrated by applying it to the one-step isolation of a trypsin
      inhibitor from a crude extract of soybean flour.

PMID- 20038086
TI  - Phase-change InSbTe nanowires grown in situ at low temperature by metal-organic
      chemical vapor deposition.
AB  - Phase-change InSbTe (IST) single crystalline nanowires were successfully
      synthesized at a low temperature of 250 degrees C by metalorganic chemical vapor
      deposition (MOCVD). The growth of IST nanowires by MOCVD, at very high working
      pressure, was governed by supersaturation. The growth mechanism of the IST
      nanowires by MOCVD is addressed in this paper. Under high working pressure, the
      InTe phase was preferentially formed on the TiAlN electrode, and the InTe
      protrusions were nucleated on the InTe films under high supersaturation. The Sb
      was continuously incorporated into the InTe protrusions, which was grown as an
      IST nanowire. Phase-change-induced memory switching was realized in IST nanowires
      with a threshold voltage of about 1.6 V. The ability to grow IST nanowires at low
      temperature by MOCVD should open opportunities for investigation of the nanoscale
      phase-transition phenomena.

PMID- 20038084
TI  - Sensitive and rapid method for amino acid quantitation in malaria biological
      samples using AccQ.Tag ultra performance liquid chromatography-electrospray
      ionization-MS/MS with multiple reaction monitoring.
AB  - An AccQ*Tag ultra performance liquid chromatography-electrospray ionization
      tandem mass spectrometry (AccQ*Tag-UPLC-ESI-MS/MS) method for fast, reproducible,
      and sensitive amino acid quantitation in biological samples, particularly, the
      malaria parasite Plasmodium falciparum is presented. The Waters Acquity TQD
      UPLC/MS system equipped with a photodiode array (PDA) detector was used for amino
      acid separation and detection. The method was developed and validated using amino
      acid standard mixtures containing acidic, neutral, and basic amino acids. For MS
      analysis, the optimum cone voltage implemented, based on direct infusion analysis
      of a few selected AccQ*Tag amino acids with multiple reaction monitoring, varied
      from 29 to 39 V, whereas the collision energy varied from 15 to 35 V. Calibration
      curves were built using both internal and external standardization. Typically, a
      linear response for all amino acids was observed at concentration ranges of 3 x
      10(-3)-25 pmol/muL. For some amino acids, concentration limits of detection were
      as low as 1.65 fmol. The coefficients of variation for retention times were
      within the range of 0.08-1.08%. The coefficients of variation for amino acid
      quantitation, determined from triplicate UPLC-MS/MS runs, were below 8% on the
      average. The developed AccQ*Tag-UPLC-ESI-MS/MS method revealed good technical and
      biological reproducibility when applied to P. falciparum and human red blood
      cells samples. This study should provide a valuable insight into the performance
      of UPLC-ESI-MS/MS for amino acid quantitation using AccQ*Tag derivatization.

PMID- 20038087
TI  - Photo-thermoelectric effect at a graphene interface junction.
AB  - We investigate the optoelectronic response of a graphene single-bilayer interface
      junction using photocurrent (PC) microscopy. We measure the polarity and
      amplitude of the PC while varying the Fermi level by tuning a gate voltage. These
      measurements show that the generation of PC is by a photothermoelectric effect.
      The PC displays a factor of approximately 10 increase at the cryogenic
      temperature as compared to room temperature. Assuming the thermoelectric power
      has a linear dependence on the temperature, the inferred graphene thermal
      conductivity from temperature dependent measurements has a T(1.5) dependence
      below approximately 100 K, which agrees with recent theoretical predictions.

PMID- 20038088
TI  - Gd(III)-nanodiamond conjugates for MRI contrast enhancement.
AB  - A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized,
      enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles
      significantly reduced the T(1) of water protons with a per-Gd(III) relaxivity of
      58.82 +/- 1.18 mM(-1) s(-1) at 1.5 T (60 MHz). This represents a 10-fold increase
      compared to the monomer Gd(III) complex (r(1) = 5.42 +/- 0.20 mM(-1) s(-1)) and
      is among the highest per-Gd(III) relaxivities reported.

PMID- 20038089
TI  - Supervised self organizing maps for classification and determination of
      potentially discriminatory variables: illustrated by application to nuclear
      magnetic resonance metabolomic profiling.
AB  - The article describes the extension of the self organizing maps discrimination
      index (SOMDI) for cases where there are more than two classes and more than one
      factor that may influence the group of samples by using supervised SOMs to
      determine which variables and how many are responsible for the different types of
      separation. The methods are illustrated by an application in the area of
      metabolic profiling, consisting of a nuclear magnetic resonance (NMR) data set of
      96 samples of human saliva, which is characterized by three factors, namely,
      whether the sample has been treated or not, 16 donors, and 3 sampling days,
      differing for each donor. The sampling days can be considered a null factor as
      they should have no significant influence on the metabolic profile. Methods for
      supervised SOMs involve including a classifier for organizing the map, and we
      report a method for optimizing this by using an additional weight that determines
      the relative importance of the classifier relative to the overall experimental
      data set in order to avoid overfitting. Supervised SOMs can be obtained for each
      of the three factors, and we develop a multiclass SOM discrimination index
      (SOMDI) to determine which variables (or regions of the NMR spectra) are
      considered significant for each of the three potential factors. By dividing the
      data iteratively into training and test sets 100 times, we define variables as
      significant for a given factor if they have a positive SOMDI in the training set
      for the factor and class of interest over all iterations.

PMID- 20038090
TI  - Electrospray-assisted ultraviolet aerodynamic particle sizer spectrometer for
      real-time characterization of bacterial particles.
AB  - The ultraviolet aerodynamic particle sizer (UVAPS) spectrometer is a novel,
      commercially available aerosol counter for real-time, continuous monitoring of
      viable bioaerosols based on the fluorescence induced from living microorganisms.
      For aerosolization of liquid-based microorganisms, general aerosolization methods
      such as atomization or nebulization may not be adequate for an accurate and
      quantitative characterization of the microorganisms because of the formation of
      agglomerated particles. In such cases, biological electrospray techniques have an
      advantage because they generate nonagglomerated particles, attributable to the
      repulsive electrical forces among particles with unipolar charges. Biological
      electrosprays are quickly gaining potential for the detection and control of
      living organisms in applications ranging from mass spectrometry to developmental
      microbiology. In this study, we investigated the size distribution, total
      concentration, and fluorescence percentage of bacterial particles in a real-time
      manner by electrospray-assisted UVAPS. A suspension containing Escherichia coli
      as a test microorganism was sprayed in a steady cone-jet mode using a specially
      designed electrospray system with a point-to-orifice-plate configuration based on
      charge-reduced electrospray size spectrometry. With the electrospray process, 98%
      of the total E. coli particle number concentration had a size of <1 mum and the
      geometric mean diameter was 0.779 mum, as compared with the respective values of
      78% and 0.907 mum after nebulization. The fractions of fluorescence responsive
      particles and of particles that contained viable organisms in culture were 12%
      and 7%, respectively, from the electrospray process and 34% and 24% from
      nebulization. These results demonstrate that (1) the presence of agglomerated
      particles can lead to markedly overestimated fluorescence and culturability
      percentages compared with the values obtained from nonagglomerated particles, and
      (2) electrospray-assisted UVAPS can provide more accurate and quantitative real
      time characterization of liquid-based microorganisms, owing to the generation of
      nonagglomerated particles.

PMID- 20038091
TI  - Phosphorescent oxygen sensors based on nanostructured polyolefin substrates.
AB  - New phosphorescent oxygen-sensitive materials based on nanostructured high
      density polyethylene and polypropylene films are described. The polymer
      substrates undergo treatment by a solvent crazing process to create a well
      developed network of controlled, nanometer-size pores. Indicator dye molecules
      are then embedded by physical entrapment in such nanostructures which
      subsequently can be healed. Such sensors demonstrate improved working
      characteristics and allow simple, cost-efficient production and disposable use.
      They are well suited for large-scale applications such as nondestructive control
      of residual oxygen and "smart" packaging.

PMID- 20038092
TI  - Modification of electrode surfaces: deposition of thin layers of polypyrrole--Au
      nanoparticle materials using a combination of interphase synthesis and dip-in
      method.
AB  - Formation of thin layers of the composite material by a method based on
      interphase polymerization induced by a transport-controlled redox reaction is
      described. The obtained films were of 0.2-1 microm thickness, consisted of
      polypyrrole and gold nanoparticles (up to 13.5 at. %), strongly adhered to the
      substrate surface, and were uniform. Different carbon materials and glass wool
      were employed as the substrates. The first step in the synthesis was deposition
      of an organic layer on the substrate. This was followed by dipping the substrate
      in an aqueous solution containing an oxidizer and appropriate washing and drying
      the composite film.

PMID- 20038093
TI  - Fluorescent-dye-doped sol-gel sensor for highly sensitive carbon dioxide gas
      detection below atmospheric concentrations.
AB  - Optical fluorescence sol-gel sensors have been developed for the detection of
      carbon dioxide gas in the 0.03-30% range with a detection limit of 0.008% (or 80
      ppm) and a quantitation limit of 0.02% (or 200 ppm) CO(2). Sol-gels were spin
      coated on glass slides to create an organically modified silica-doped matrix with
      the 1-hydroxypyrene-3,6,8-trisulfonate (HPTS) fluorescent indicator. The
      luminescence intensity of the HPTS indicator (513 nm) is quenched by CO(2), which
      protonates the anionic form of HPTS. An ion pair technique was used to
      incorporate the lipophilic dye into the hydrophilic sol-gel matrix. TiO(2)
      particles (<5 microm diameter) were added to induce Mie scattering and increase
      the incident light interaction with the sensing film, thus increasing the signal
      to-noise ratio. Moisture-proof overcoatings have been used to maintain a constant
      level of water inside the sensor films. The optical sensors are inexpensive to
      prepare and can be easily coupled to fiber optics for remote sensing
      capabilities. A fiber-optic bundle was used for the gas detection and shown to
      work as part of a multianalyte platform for simultaneous detection of multiple
      analytes. The studies reported here resulted in the development of sol-gel
      optical fluorescent sensors for CO(2) gas with sensitivity below that in the
      atmosphere (ca. 387 ppm). These sensors are a complementary approach to current
      FT-IR measurements for real-time carbon dioxide detection in environmental
      applications.

PMID- 20038094
TI  - Part-per-trillion determination of pharmaceuticals, pesticides, and related
      organic contaminants in river water by solid-phase extraction followed by
      comprehensive two-dimensional gas chromatography time-of-flight mass
      spectrometry.
AB  - An analytical procedure based on comprehensive two-dimensional gas chromatography
      (GC x GC) coupled with time-of-flight mass spectrometry (TOF-MS) for the
      simultaneous determination of 97 organic contaminants at trace concentration in
      river water is presented. The target analytes included 13 pharmaceuticals, 18
      plasticizers, 8 personal care products, 9 acid herbicides, 8 triazines, 10
      organophosphorous compounds, 5 phenylureas, 12 organochlorine biocides, 9
      polycyclic aromatic hydrocarbons (PAHs), and 5 benzothiazoles and benzotriazoles.
      The best resolution of the target analytes in the contour plots was obtained when
      a nonpolar stationary phase was used in the first dimension and polar one in the
      second. However, in the opposite configuration, polar-nonpolar, the retention
      time in the second dimension exhibited a strong correlation with the log Kow (p <
      0.01), and it was proposed as an additional identification criteria. The
      developed methodology is based on a polymeric solid-phase extraction followed by
      in GC-port methylation and GC x GC/TOF-MS determination. Moreover, limits of
      detection (LODs) and quantification (LOQs) ranged from 0.5 to 100 ng/L and from 2
      to 185 ng/L, respectively. Repeatability was always lower than 20%. Finally, the
      developed method has been successfully applied to the determination of incurred
      target analytes in four river waters subjected to a different anthropogenic
      pressure.

PMID- 20038095
TI  - MNAzymes, a versatile new class of nucleic acid enzymes that can function as
      biosensors and molecular switches.
AB  - To increase the versatility and utility of nucleic acid enzymes, we developed
      multicomponent complexes, known as MNAzymes, which produce amplified "output"
      signals in response to specific "input" signals. Multiple oligonucleotide
      partzymes assemble into active MNAzymes only in the presence of an input assembly
      facilitator such as a target nucleic acid. Once formed, MNAzymes catalytically
      modify a generic substrate, generating an amplified output signal that heralds
      the presence of the target while leaving the target intact. We demonstrated
      several applications including sensitive, isothermal target detection;
      discrimination of polymorphisms; and highly specific monitoring of real-time
      polymerase chain reaction (PCR). Furthermore, we showed their capacity to
      function as molecular switches and to work in series to create a molecular
      cascade. The modular nature of MNAzymes, together with the separation of input
      and output functionalities, provides potential for their integration into diverse
      devices such as diagnostic biosensors, molecular computers, and/or nanoscale
      machines.

PMID- 20038097
TI  - Pd-catalyzed intramolecular acylation of aryl bromides via C-H functionalization:
      a highly efficient synthesis of benzocyclobutenones.
AB  - A new catalyst system for the intramolecular acylation of aldehydes with aryl
      bromides via C-H functionalization is described. The transformation is
      distinguished by a remarkable functional group tolerance and hence allows for the
      synthesis of a wide variety of highly functionalized benzocyclobutenones with a
      diverse set of substitution patterns from simple and easily accessible
      precursors.

PMID- 20038096
TI  - 13C ENDOR reveals that the D1 polypeptide C-terminus is directly bound to Mn in
      the photosystem II oxygen evolving complex.
AB  - Antiferromagnetically coupled Mn(III)Mn(IV) dimers have been commonly used to
      study biological systems that exhibit complex exchange interactions. Such is the
      case for the oxygen evolving complex (OEC) in photosystem II (PSII), where we
      have studied whether the C-terminal carboxylate of D1-Ala344 is directly bound to
      the Mn cluster. To probe these protein-derived carboxylate hyperfine
      interactions, which give direct bonding information, Q-band (34 GHz) Mims ENDOR
      was performed on a Mn(III)Mn(IV) dimer ([Mn(III)Mn(IV)(mu-O)(2)mu
      OAc(TACN)(2)](BPh(4))(2)) (1) that was labeled with (13)C (I = (1)/(2)) at the
      carboxylate position of the acetate bridge. A(dip) is computed based on atomic
      coordinates from available X-ray crystal structures to be [-2.4, -0.8, 3.2] MHz.
      The value for A(iso) was determined based on simulation of the experimental ENDOR
      data, for complex 1 A(iso) = -1 MHz. Similar studies were then performed on PSII
      from Synechocystis sp. PCC 6803, in which all alanine-derived C=O groups are
      labeled with (13)C including the C-terminal alpha-COO(-) group of D1 (Ala344), as
      well as PSII proteins uniformly labeled with (13)C. Using recent X-ray
      crystallography data from T. elongatus the values for A(dip) were calculated and
      simulations of the experimental data led to A(iso) values of 1.2, 1, and 2 MHz,
      respectively. We infer from complex 1 that an A(iso) significantly larger than
      1.2 MHz for a Mn-coordinating carboxylate moiety is unlikely. Therefore, we
      support the closer arrangement of Ala344 suggested by the Loll and Guskov
      structures and conclude that the C-terminal carboxylate of D1 polypeptide is
      directly bound to the Mn cluster.

PMID- 20038098
TI  - Tissue deposition and residue depletion in lambs exposed to melamine and cyanuric
      acid-contaminated diets.
AB  - Many countries have introduced maximum residue limits for melamine in foods since
      its adulteration in infant formula in China. However, more animal feeding studies
      are needed to understand the fate of melamine-contaminated animal feed. In this
      study, the melamine contents in tissues and serum were tested using LC-MS/MS for
      up to 60 days for lambs fed with diets containing 2-100 mg of melamine per kg of
      diet. A higher dose of melamine in the diet resulted in a higher concentration in
      tissues and serum, with the maximum melamine content in the kidney. When cyanuric
      acid was coadministered at an equal concentration to that of melamine, the
      deposition of melamine in lambs was similar to the treatment with melamine only
      and was much higher than the deposition of cyanuric acid. When melamine was
      withdrawn from the diet, melamine concentrations decreased below 20 microg/kg in
      all tissues after 4 days. The present study may provide available information for
      future work about the risk assessment of melamine to human health.

PMID- 20038099
TI  - Antifungal activity of 4'-(2,6,6-Trimethyl-2-cyclohexen-1-yl)-3'-butene-2'
      ketoxime N-O-alkyl ethers.
AB  - A number of 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-butene-2'-ketoxime N-O
      alkyl ethers were prepared, separated into their E and Z isomers, and
      characterized on the basis of (1)H NMR and mass spectroscopy. These compounds
      were tested in vitro for antifungal activity against four important
      phytopathogenic fungi, namely, Sclerotium rolfsii , Rhizoctonia bataticola ,
      Macrophomina phaseolina , and Sclerotinia sclerotiorum . E isomers of 4'-(2,6,6
      trimethyl-2-cyclohexen-1-yl)-3'-butene-2'-ketoxime N-O-propyl ether (ED(50) =
      32.36 microg mL(-1)) and 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-butene-2'
      ketoxime N-O-(1''-methyl) ethyl ether (ED(50) = 35.50 microg mL(-1)) showed
      maximum antifungal activity against R. bataticola and S. rolfsii, respectively,
      whereas 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-butene-2'(Z)-ketoxime N-O
      pentyl ether was found to be active against M. phaseolina (ED(50) = 31.08 microg
      mL(-1)) and S. sclerotiorum (ED(50) 21.39 microg mL(-1)), respectively. The Z
      isomer of 4'-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3'-butene-2'-ketoxime N-O-pentyl
      ether, which was found to be most effective, was tested against S. sclerotiorum
      in a greenhouse at 1 and 5% concentrations. The 5% aqueous emulsion of 4'-(2,6,6
      trimethyl-2-cyclohexen-1-yl)-3'-butene-2'(Z)-ketoxime N-O-pentyl ether suppressed
      disease development in pea by 90-95% as compared with the untreated infested soil
      in the greenhouse after 21 days of treatment.

PMID- 20038100
TI  - HPLC-MS analysis of proanthocyanidin oligomers and other phenolics in 15
      strawberry cultivars.
AB  - The phenolic compounds of 15 strawberry cultivars grown in Spain were analyzed
      and quantified: anthocyanins (20.2-47.4 mg/100 g of fw) (cyanidin 3-glucoside and
      pelargonidin 3-glucoside, 3-rutinoside, and 3-malonyl glucoside), flavonols (1.5
      3.4 mg/100 g of fw) (quercetin 3-glucuronide and kaempferol 3-glucoside and 3-p
      coumaroyl-glucoside), proanthocyanidins (53.9-163.2 mg/100 g), p-coumaroyl
      glucose (0.84-6.70 mg/100 g), ellagitannins (9.67-22.86 mg/100 g) (sanguiin H-6,
      lambertianin C, and galloyl bis-HHDP-glucose), and ellagic acid glycosides (0.88
      2.06 mg/100 g of fw) (two ellagic acid deoxyhexosides). Proanthocyanidins, the
      main phenolic compounds, were characterized by phloroglucinol degradation. Their
      mean degree of polymerization ranged from 3.4 for cv. Chiflon to 5.8 for cv.
      Ventana, the average value being 4.3. The terminal unit of proanthocyanidin
      oligomers was always (epi)catechin (17.36-29.93%) and (epi)catechin (61.66
      75.39%) or (epi)afzelechin (4.50-10.54%) as extension units. Different
      combinations of (epi)catechin and (epi)afzelechin were detected, and their
      sequence of linkage was characterized by HPLC-MS-MS. Relative percentages of
      dimers, trimers, tetramers, and pentamers were evaluated by the extracted ion
      chromatogram (EIC) analysis.

PMID- 20038101
TI  - Starch molecular structure shows little association with fruit physiology and
      starch metabolism in tomato.
AB  - The aim of this work was to determine if the molecular structure of starch from
      tomato ( Solanum lycopersicum L.) is influenced by fruit physiology and
      carbohydrate metabolism. The effect of fruit size, fruit ripening behavior, and
      assimilate availability on starch granule accumulation was examined in nine
      tomato samples. The percentage of (14)C-glucose partitioning to starch was
      similar among samples, but starch contents varied 10-fold, suggesting differences
      in metabolism. In contrast, granule size (10-20 microm), amylose content (19
      23%), degree of crystallinity (26-31%), and enthalpy of gelatinization (14.8-17.2
      degrees C) were similar. Some differences in structure were detected in starch
      from the largest and smallest fruit using more sensitive analyses such as thermal
      properties, chain length distribution of amylopectin, and susceptibility to in
      vitro alpha-amylase digestion. However, overall, our results suggest that granule
      characteristics are highly conserved in tomato fruit, and we conclude that this
      is likely due to inherent metabolic constraints.

PMID- 20038102
TI  - Highly sequence-dependent formation of fluorescent silver nanoclusters in
      hybridized DNA duplexes for single nucleotide mutation identification.
AB  - Fluorescent silver nanoclusters were successfully synthesized using hybridized
      DNA duplexes as capping scaffolds. The formation of these emitters was highly
      sequence-dependent and could specifically identify a single nucleotide mutation,
      the sickle cell anemia gene mutation. Furthermore, the identification of single
      nucleotide differences using this strategy was extended to more general types of
      single-nucleotide mismatches.

PMID- 20038103
TI  - Theoretical analysis of factors controlling Pd-catalyzed decarboxylative coupling
      of carboxylic acids with olefins.
AB  - Transition-metal-catalyzed decarboxylative coupling presents a new and important
      direction in synthetic chemistry. Mechanistic studies on decarboxylative coupling
      not only improve the understanding of the newly discovered transformations, but
      also may have valuable implications for the development of more effective
      catalyst systems. In this work, a comprehensive theoretical study was conducted
      on the mechanism of Myers' Pd-catalyzed decarboxylative Heck reaction. The
      catalytic cycle was found to comprise four steps: decarboxylation, olefin
      insertion, beta-hydride elimination, and catalyst regeneration. Decarboxylation
      was the rate-limiting step, and it proceeded through a dissociative pathway in
      which Pd(II) mediated the extrusion of CO(2) from an aromatic carboxylic acid to
      form a Pd(II)-aryl intermediate. Further analysis was conducted on the factors
      that might control the efficiency of Myers' decarboxylative Heck reaction. These
      factors included Pd salts, ligands, acid substrates, and metals. (1) Regarding Pd
      salts, PdCl(2) and PdBr(2) were worse catalysts than Pd(TFA)(2), because the
      exchange of Cl or Br by a carboxylate from Pd was thermodynamically unfavorable.
      (2) Regarding ligands, DMSO provided the best compromise between carboxyl
      exchange and decarboxylation. Phosphines and N-heterocarbenes disfavored
      decarboxylation because of their electron richness, whereas pyridine ligands
      disfavored carboxyl exchange. (3) Regarding acid substrates, a good correlation
      was observed between the energy barrier of R-COOH decarboxylation and the R-H
      acidity. Substituted benzoic acids showed deviation from the correlation because
      of the involvement of pi(substituent)-sigma(C(ipso)-Pd) interaction. (4)
      Regarding metals, Ni and Pt were worse catalysts than Pd because of the less
      favorable carboxyl exchange and/or DMSO removal steps in Ni and Pt catalysis.

PMID- 20038104
TI  - Flavonoids from the buds of Rosa damascena inhibit the activity of 3-hydroxy-3
      methylglutaryl-coenzyme a reductase and angiotensin I-converting enzyme.
AB  - Rosa damascena has been manufactured as various food products, including tea, in
      Korea. A new flavonoid glycoside, kaempferol-3-O-beta-D-glucopyranosyl(1-->4)
      beta-D-xylopyranoside, named roxyloside A was isolated from the buds of this
      plant, along with four known compounds, isoquercitrin, afzelin, cyanidin-3-O-beta
      glucoside, and quercetin gentiobioside. The chemical structures of these
      compounds were determined by spectroscopic analyses, including FAB-MS, UV, IR,
      (1)H and (13)C NMR, DEPT, and 2D NMR (COSY, HSQC, and HMBC). All the isolated
      compounds except cyanidin-3-O-beta-glucoside exhibited high levels of inhibitory
      activity against 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase with
      IC(50) values ranging from 47.1 to 80.6 microM. Cyanidin-3-O-beta-glucoside
      significantly suppressed angiotensin I-converting enzyme (ACE) activity, with an
      IC(50) value of 138.8 microM, while the other four compounds were ineffective.
      These results indicate that R. damascena and its flavonoids may be effective to
      improve the cardiovascular system.

PMID- 20038105
TI  - Potent inhibitors of furin and furin-like proprotein convertases containing
      decarboxylated P1 arginine mimetics.
AB  - Furin belongs to the family of proprotein convertases (PCs) and is involved in
      numerous normal physiological and pathogenic processes, such as viral
      propagation, bacterial toxin activation, cancer, and metastasis. Furin and
      related furin-like PCs cleave their substrates at characteristic multibasic
      consensus sequences, preferentially after an arginine residue. By incorporating
      decarboxylated arginine mimetics in the P1 position of substrate analogue
      peptidic inhibitors, we could identify highly potent furin inhibitors. The most
      potent compound, phenylacetyl-Arg-Val-Arg-4-amidinobenzylamide (15), inhibits
      furin with a K(i) value of 0.81 nM and has also comparable affinity to other PCs
      like PC1/3, PACE4, and PC5/6, whereas PC2 and PC7 or trypsin-like serine
      proteases were poorly affected. In fowl plague virus (influenza A, H7N1)-infected
      MDCK cells, inhibitor 15 inhibited proteolytic hemagglutinin cleavage and was
      able to reduce virus propagation in a long-term infection test. Molecular
      modeling revealed several key interactions of the 4-amidinobenzylamide residue in
      the S1 pocket of furin contributing to the excellent affinity of these
      inhibitors.

PMID- 20038107
TI  - New strategy for synthesis and functionalization of carbon nanoparticles.
AB  - We describe a novel "one-step" combined synthesis and functionalization of carbon
      nanoparticles, using a new generation of all-in-one small submerged-arc plasma
      reactor that we have developed. We take advantage of long-lived free radicals
      generated by a submerged-arc helium atmosphere plasma and resident on the
      nanoparticle surfaces to supply ethylenediamine directly after the plasma to
      functionalize the carbon nanoparticles. XPS, TG/DTG, FTIR, and fluorescence tests
      confirm the viability of this new amination process. The nanoparticles are small
      and relatively uniformly sized. Their dispersibility in aqueous solution is
      significant.

PMID- 20038106
TI  - Development of (S)-N6-(2-(4-(isoquinolin-1-yl)piperazin-1-yl)ethyl)-N6-propyl
      4,5,6,7-tetrahydrobenzo[d]-thiazole-2,6-diamine and its analogue as a D3 receptor
      preferring agonist: potent in vivo activity in Parkinson's disease animal models.
AB  - Here we report structure-activity relationship study of a novel hybrid series of
      compounds where structural alteration of aromatic hydrophobic moieties connected
      to the piperazine ring and bioisosteric replacement of the aromatic tetralin
      moieties were carried out. Binding assays were carried out with HEK-293 cells
      expressing either D2 or D3 receptors with tritiated spiperone to evaluate
      inhibition constants (K(i)). Functional activity of selected compounds in
      stimulating GTPgammaS binding was assessed with CHO cells expressing human D2
      receptors and AtT-20 cells expressing human D3 receptors. SAR results identified
      compound (-)-24c (D-301) as one of the lead molecules with preferential agonist
      activity for D3 receptor (EC(50) (GTP gamma S); D3 = 0.52 nM; D2/D3 (EC(50)):
      223). Compounds (-)-24b and (-)-24c exhibited potent radical scavenging activity.
      The two lead compounds, (-)-24b and (-)-24c, exhibited high in vivo activity in
      two Parkinson's disease (PD) animal models, reserpinized rat model and 6-OHDA
      induced unilaterally lesioned rat model. Future studies will explore potential
      use of these compounds in the neuroprotective therapy for PD.

PMID- 20038108
TI  - Novel synthesis and structural characterization of a high-affinity paramagnetic
      kinase probe for the identification of non-ATP site binders by nuclear magnetic
      resonance.
AB  - To aid in the pursuit of selective kinase inhibitors, we have developed a unique
      ATP site binder tool for the detection of binders outside the ATP site by nuclear
      magnetic resonance (NMR). We report here the novel synthesis that led to this
      paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar
      inhibitory activity against multiple kinases. We demonstrate the application of
      this probe by performing NMR binding experiments with Lck and Src kinases and
      utilize it to detect the binding of two compounds proximal to the ATP site. The
      complex structure of the probe with Lck is also presented, revealing how the
      probe fits in the ATP site and the specific interactions it has with the protein.
      We believe that this spin-labeled probe is a valuable tool that holds broad
      applicability in a screen for non-ATP site binders.

PMID- 20038109
TI  - Cyclobutane amino acid analogues of furanomycin obtained by a formal [2 + 2]
      cycloaddition strategy promoted by methylaluminoxane.
AB  - The synthesis and conformational analysis of a new type of conformationally
      restricted alpha-amino acid analogue of the amino acid antibiotic furanomycin is
      presented. The restriction involves the cis-fused cyclobutane and tetrahydrofuran
      units, generating the unusual 2-oxabicyclo[3.2.0]heptane core, which is found in
      a great number of biologically active natural products. The synthetic strategy is
      based on a formal [2 + 2] cycloaddition between 2-(acylamino)acrylates as
      acceptor alkenes and 2,3-dihydrofuran as a donor alkene, promoted by bulky
      aluminum-derived Lewis acids, particularly by methylaluminoxane (MAO).
      Additionally, following the same strategy, the synthesis of furanomycin analogues
      incorporating the 2-oxabicyclo[4.2.0]octane is reported.

PMID- 20038110
TI  - Chemical bonding in transition metal complexes with beryllium ligands
      [(PMe(3))(2)M-BeCl(2)], [(PMe(3))(2)M-BeClMe], and [(PMe(3))(2)M-BeMe(2)] (M =
      Ni, Pd, Pt).
AB  - The equilibrium geometries and bond dissociation energies of the 14 valence
      electron (VE) complexes [(PMe(3))(2)M-BeCl(2)], [(PMe(3))(2)M-BeClMe], and
      [(PMe(3))(2)M-BeMe(2)] with M = Ni, Pd, and Pt have been calculated using density
      functional theory at the BP86/TZ2P level. The nature of the M-Be bond was
      analyzed with the NBO charge decomposition analysis and the EDA energy
      decomposition analysis. The theoretical results predict the equilibrium
      structures with a T-shaped geometry at the transition metal where the PMe(3)
      ligands are in the axial positions. The calculated bond dissociation energies
      show that the M-E bond strengths are in the range of donor-acceptor complexes of
      divalent beryllium compounds with ammonia. The bond strength decreases when the
      substituent at beryllium changes from Cl to CH(3). The NBO analysis shows a
      negative charge at the BeX(2) fragment, which indicates a net charge flow from
      the transition metal fragment to the beryllium fragment. The energy decomposition
      analysis of the M-Be bonds suggests two donor-acceptor bonds with sigma and pi
      symmetry where the transition metal fragment is a double donor with respect to
      the beryllium ligand. The pi component of the [Ni]-->BeXX' donation is much
      smaller than the sigma component.

PMID- 20038111
TI  - Photoelectron circular dichroism spectroscopy in an orbitally congested system:
      the terpene endoborneol.
AB  - We have measured the photoelectron circular dichroism (PECD) of single
      enantiomers of endoborneol in the photon region from 9.9 to 23.6 eV by combining
      circularly polarized synchrotron radiation and a velocity map imaging technique.
      A photoelectron spectrum and the state-selected fragmentation curves of this
      terpene were also recorded. Unlike previous case studies, the broad featureless
      transitions encountered here preclude an orbital by orbital analysis of the PECD,
      although semiquantitative features of the highest-occupied molecular orbital PECD
      are identified and compared to full calculations. Despite our inability to
      further identify individual orbitals experimentally, we show that we are able to
      unambiguously assign the absolute configuration by comparison with realistic
      simulated PECD spectra. Furthermore, the calculations predict that for electron
      kinetic energies above 5 eV; the contributions of individual conformers to the
      PECD are nearly identical. Should this observation apply to bigger biological
      systems, the analysis could be greatly simplified by recording high kinetic
      energy electrons. On the other hand the contributions of the different conformers
      to the slow electron PECD seem to vary more significantly, and we deduce, within
      the theoretical limitations, a plausible 1:1:1 distribution of the three
      identified conformers.

PMID- 20038113
TI  - Detection and quantification of trace organic contaminants in water using the FT
      IR-attenuated total reflectance technique.
AB  - The Fourier transform infrared-attenuated total reflectance (FT-IR-ATR) technique
      has been used to detect and quantify the following volatile organic compounds
      (VOCs) in water: 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane, styrene,
      and tetrachloroethylene, among which the first three compounds were investigated
      at parts per million levels for the first time. Enhancement of the detection was
      made by (1) coating the ATR crystal with a hydrophobic polymer membrane, (2)
      optimizing the flow rate of the sample solution, (3) varying polymer membrane
      thickness, and (4) increasing the number of reflection bounces within the ATR
      crystal. Our flow rate optimization confirmed a previous finding that turbulent
      flow is more favorable than laminar flow in detecting the VOCs in water. However,
      decreases of ATR signal intensity were observed at very high turbulency due to
      analytes flowing too quickly through and exiting the ATR cell to be adsorbed onto
      the polymer membrane. The optimal membrane thickness was found to be associated
      with the maximum overlap between the IR evanescent wave penetration depth and the
      analyte diffusion depth. Consequently, there is no universal optimal flow rate
      and optimal polymer membrane thickness for detection of all VOCs. Doubling the
      number of IR reflection bounces within the ATR crystal enhanced both detection
      and sensitivity by about a factor of 2. Finally, it was observed that the
      detection limit concentrations decrease with the water solubility of the VOCs.

PMID- 20038114
TI  - Polymeric ionic liquids as CO(2) selective sorbent coatings for solid-phase
      microextraction.
AB  - Two polymeric ionic liquids (PIL) were synthesized and employed as sorbent
      coatings in solid-phase microextraction (SPME) for the selective extraction of
      CO(2). The two coatings, poly(1-vinyl-3-hexylimidazolium)
      bis[(trifluoromethyl)sulfonyl]imide [poly(VHIM-NTf(2))] and poly(1-vinyl-3
      hexylimidazolium) taurate [poly(VHIM-taurate)], exhibited varied selectivity
      toward CO(2) due to functional groups within in the PIL that imparted different
      mechanisms of CO(2) capture. Extraction efficiencies were compared to those of
      two commercial SPME fibers [poly(dimethylsiloxane) (PDMS) and Carboxen-PDMS]. The
      poly(VHIM-NTf(2)) PIL fiber exhibited comparable extraction efficiency at high
      CO(2) pressure compared to the Carboxen-PDMS fiber, even though the PIL-based
      fibers possessed much smaller film thicknesses. Calibration curves generated in
      pure CO(2) showed that the sensitivity of the poly(VHIM-NTf(2)) coating was
      comparable to that of the Carboxen-PDMS fiber with both PIL-based fibers
      exhibiting larger linear ranges and higher extraction-to-extraction
      reproducibility. The storage ability for selected fibers was examined and
      revealed that the PIL-based coatings exhibited superior capability in retaining
      the CO(2) sorbate on the fiber under different storage conditions, particularly
      for the poly(VHIM-taurate) PIL which reversibly captures CO(2) as a carbamate
      salt.

PMID- 20038112
TI  - Catalysis and inhibition of Mycobacterium tuberculosis methionine aminopeptidase.
AB  - Methionine aminopeptidase (MetAP) carries out an important cotranslational N
      terminal methionine excision of nascent proteins and represents a potential
      target to develop antibacterial and antitubercular drugs. We cloned one of the
      two MetAPs in Mycobacterium tuberculosis (MtMetAP1c from the mapB gene) and
      purified it to homogeneity as an apoenzyme. Its activity required a divalent
      metal ion, and Co(II), Ni(II), Mn(II), and Fe(II) were among activators of the
      enzyme. Co(II) and Fe(II) had the tightest binding, while Ni(II) was the most
      efficient cofactor for the catalysis. MtMetAP1c was also functional in E. coli
      cells because a plasmid-expressed MtMetAP1c complemented the essential function
      of MetAP in E. coli and supported the cell growth. A set of potent MtMetAP1c
      inhibitors were identified, and they showed high selectivity toward the Fe(II)
      form, the Mn(II)-form, or the Co(II) and Ni(II) forms of the enzyme,
      respectively. These metalloform selective inhibitors were used to assign the
      metalloform of the cellular MtMetAP1c. The fact that only the Fe(II)-form
      selective inhibitors inhibited the cellular MtMetAP1c activity and inhibited the
      MtMetAP1c-complemented cell growth suggests that Fe(II) is the native metal used
      by MtMetAP1c in an E. coli cellular environment. Finally, X-ray structures of
      MtMetAP1c in complex with three metalloform-selective inhibitors were analyzed,
      which showed different binding modes and different interactions with metal ions
      and active site residues.

PMID- 20038115
TI  - Interaction forces between microsized silica particles and weak polyelectrolyte
      brushes at varying pH and salt concentration.
AB  - The AFM colloidal probe technique was used to measure the interaction between
      microsized silica spheres and annealed polyelectrolyte brushes made of
      poly(acrylic acid) (PAA) and poly(2-vinyl pyridine) (P2VP) in KCl solutions of
      various pH values and salt concentrations. The interaction energy showed a
      distance dependence that was affected strongly by the swelling and the electric
      properties of the brushes. Between PAA brushes and silica particles, a repulsive
      interaction has been observed for all pH values and salt concentrations
      reflecting the swelling of the brush with varying pH value and the transition
      from osmotic to salted brush regime with increasing KCl concentration. Force
      measurements between P2VP brushes and silica particles revealed a much more
      complex behavior: a steric repulsion by the swollen brush at low pH values, a
      complex interplay of attractive and repulsive forces at intermediate pH values
      and a short-ranged attraction between the collapsed brush and the silica particle
      at basic pH values and high salt concentrations. The results are interpreted in
      comparison with the Alexander de Gennes model and zeta potential and
      ellipsometric measurements.

PMID- 20038116
TI  - Fc-Fc Electronic interaction through equatorial pathways of a diruthenium core.
AB  - Diruthenium compounds bearing one (3) and two (4) ferrocene carboxylate ligands
      were prepared and characterized, and the electronic coupling between two
      equatorially adjacent Fc centers in compound 4 is significant, but weaker than
      those between Fc centers placed on the opposite axial sites.

PMID- 20038117
TI  - Can the fragmentation of hydrogen-bonded dimers be predicted: predissociation of
      C2H2-HX.
AB  - HX rotational state distributions following vibrational predissociation (VP) of
      C(2)H(2)-HX (X = Cl, F, O) dimers are predicted by expressing the predissociation
      process as the joint probability of rovibrational excitation in the fragments
      following "internal collision" in the vibrationally excited dimer. Calculations
      of these joint probabilities for the T-shaped dimers of acetylene with HCl, DCl,
      HF, and OH using the angular momentum (AM) method reproduce experimental
      distributions with reasonable accuracy. In dimers of this complex, many different
      pathways for the disposal of initial energy and momentum exist in principle. The
      use of simple physical arguments based on (a) the direction of initial impulse
      upon excitation and (b) restricted relative geometries due to limited amplitude
      of relative motion of the dimer components allows the number of effective
      dissociation pathways to be much reduced. For these, the probability of
      rotational and rovibrational transfer into the fragments is calculated, a process
      that generally involves summing over a number of C(2)H(2) rovibrational states
      for each value of j(HX). In calculating relative rotational populations in the
      fragments, it was found essential to first calculate the threshold value of
      available energy for that transition and the threshold value of b(n), the
      effective impact parameter. Without these modifications, channels of lowest j(HX)
      and/or j(C(2)H(2)) dominate, which generally is not found experimentally. The
      need for these modifications is attributed to energy conservation in the
      dissociation and the limited range of relative orientations that the dimer pair
      can explore. The AM method is able to predict the very different fragment
      rotational excitations in this series of dimers fairly well using only readily
      available data. In addition, a number of new insights into the physical
      principles that control the dissociation of molecule-molecule dimers have emerged
      and are discussed. The results suggest that each fragment quantum state pair
      results from a very specific relative geometry of dissociation and that the
      balance between vibrational and rotational excitations is determined by the
      requirement to restrict the angular momentum "load" in the predissociation.

PMID- 20038118
TI  - Bipolar host molecules for efficient blue electrophosphorescence: a quantum
      chemical design.
AB  - On the basis of density functional theory (DFT) calculations, a new series of
      bipolar host molecules for efficient blue electrophosphorescence devices are
      designed by linkage of hole-transporting moiety carbazole (CZ) and electron
      transporting unit diphenylphosphoryl (ph(2)P horizontal lineO) to the core
      molecules with high triplet energies. The electronic structures in the ground
      states, cationic and anionic states, and lowest triplet states of the designed
      molecules have been studied with emphasis on triplet energies, spin density
      distributions, ionization potentials, electron affinities, and the influence of
      molecular topology. Designed bipolar host molecules possess the following
      features: (1) relatively higher highest occupied molecular orbital (HOMO) for
      hole injection and, relatively lower lowest unoccupied molecular orbital (LUMO)
      for electron injection; (2) HOMO and LUMO separation and localization in the
      respective hole- and electron-transporting moieties; (3) dramatic bond length
      changes in ionic states occurring at different parts of the bipolar molecules
      with respect to their neutral states; (4) keeping higher triplet energy. The DFT
      results provide deep insight into the nature of bipolar molecules and show that
      the designed molecules are feasible to meet the requirements of the host
      materials for blue triplet emissions.

PMID- 20038119
TI  - Polymerization of macrocyclic phospholipid- and surfactant-based vesicles.

PMID- 20038120
TI  - Unusually high aromaticity and diatropicity of bond-alternate benzene.
AB  - Enormous effort has been devoted to the elucidation of possible effects of bond
      length alternation on the benzene pi-system. Benzene tends to stay highly
      aromatic and highly diatropic even if strong bond-length alternation is
      introduced artificially into the pi-system. Such peculiar aromatic and magnetic
      characters of benzene were justified consistently and unambiguously within a
      single theoretical framework. From all physically sound points of view, bond
      alternate benzene is highly aromatic with a large aromatic stabilization energy.
      We confirmed that in the annulene family benzene is least sensitive in
      aromaticity to bond-length alternation.

PMID- 20038121
TI  - Inverted sandwich type dinuclear chromium(I) complex and its analogues of
      scandium(I), titanium(I), vanadium(I), manganese(I), and iron(I): theoretical
      study of electronic structure and bonding nature.
AB  - Inverted sandwich type chromium(I) complexes, (mu-eta(6):eta(6)
      C(6)H(5)CH(3))[Cr(DDP)](2) (DDPH = 2-(4-{(2,6-diisopropylphenyl)imino}pent-2-ene)
      and (mu-eta(6):eta(6)-C(6)H(5)CH(3))[V(DDP)](2), synthesized by Tsai et al., and
      (mu-eta(6):eta(6)-C(6)H(6))[Cr(DDP)](2) synthesized by Monillas et al., were
      theoretically investigated with MRMP2 and DFT methods, where model compounds (mu
      eta(6):eta(6)-C(6)H(6))[Cr(AIP)](2) (AIPH = (Z)-1-amino-3-imino-prop-1-ene) were
      mainly employed. Both computational methods succeeded in reproducing the
      experimental facts that the chromium and vanadium complexes take surprisingly
      high spin states, septet and quintet spin states, respectively. MO diagrams of
      these complexes present a clear understanding of the reasons why they take such
      high spin states. We also calculated their analogues, (mu-eta(6):eta(6)
      C(6)H(6))[M(DDP)](2) (M = Sc, Ti, Mn, or Fe). The spin multiplicities of the Sc
      and Ti complexes were calculated to be singlet and triplet, respectively, by the
      DFT(B3LYP) method. Those of Mn and Fe complexes were calculated to be quintet and
      triplet, respectively, by the DFT(B3LYP) method, but nonet and singlet,
      respectively, by the MRMP2 method, suggesting that the DFT method cannot be
      applied to these complexes. The MRMP2 calculations indicate that the spin
      multiplicity increases upon going to Mn from Sc and reaches the maximum, nonet
      spin state, at Mn, and then suddenly decreases to singlet at Fe. This interesting
      change in spin multiplicity is discussed in terms of occupation of MOs.

PMID- 20038122
TI  - Oxidation state characterization of ruthenium 2-iminoquinone complexes through
      experimental and theoretical studies.
AB  - The synthesis of complexes [Ru(II)(trpy)(2-imino-4-tert-butylquinone)(Cl)](+) and
      [Ru(II)(trpy)(NIL)(OAc)](+) (where trpy = 2:2',6':2''-terpyridyl, NIL = 2-imino-4
      tert-butylquinone, 2-imino-4-methylquinone, 2-iminoquinone, 2-imino-4
      chloroquinone, 2-imino-5-chloroquinone, 2-imino-4,6-di-tert-butyl-N-phenyl
      quinone, 2-imino-4,6-di-tert-butyl-N-(2'-trifluoromethylphenyl)-quinone) is
      reported. The oxidation states of these complexes, as well as the previously
      reported [Ru(III)(trpy)(2-iminosemiquinone)(Cl)](+) complex, are investigated by
      spectroscopic, electrochemical and theoretical methods resulting in the latter
      complex being reassigned as [Ru(II)(trpy)(2-iminoquinone)(Cl)](+). Evidence for
      the presence of two structural isomers was found for all complexes, and crystal
      structures for both isomers of the [Ru(II)(trpy)(2-imino-4-tert
      butylquinone)(Cl)]ClO(4) complex are reported, as well as for the cis isomer of
      [Ru(II)(trpy)(2-imino-4,6-di-tert-butyl-N-phenyl-quinone)(OAc)]PF(6). Redox
      control is also demonstrated based on the Hammett parameters of the substituents
      on the 2-iminoquinone ligand.

PMID- 20038123
TI  - Measurement of both the equilibrium constant and rate constant for electronic
      energy transfer by control of the limiting kinetic regimes.
AB  - Electronic energy transfer can fall into two limiting cases. When the rate of the
      energy transfer back reaction is much faster than relaxation of the acceptor
      excited state, equilibrium between the donor and acceptor excited states is
      achieved and only the equilibrium constant for the energy transfer can be
      measured. When the rate of the back reaction is much slower than relaxation of
      the acceptor, the energy transfer is irreversible and only the forward rate
      constant can be measured. Herein, we demonstrate that with trans-[Cr(d(4)
      cyclam)(CN)(2)](+) as the donor and either trans-[Cr([15]ane-ane-N(4))(CN)(2)](+)
      or trans-[Cr(cyclam)(CN)(2)](+) as the acceptor, both limits can be obtained by
      control of the donor concentration. The equilibrium constant and rate constant
      for the case in which trans-[Cr([15]ane-ane-N(4))(CN)(2)](+) is the acceptor are
      0.66 and 1.7 x 10(7) M(-1) s(-1), respectively. The equilibrium constant is in
      good agreement with the value of 0.60 determined using the excited state energy
      gap between the donor and acceptor species. For the thermoneutral case in which
      trans-[Cr(cyclam)(CN)(2)](+) is the acceptor, an experimental equilibrium
      constant of 0.99 was reported previously, and the rate constant has now been
      measured as 4.0 x 10(7) M(-1) s(-1).

PMID- 20038124
TI  - Nature of guanine oxidation in RNA via the flash-quench technique versus direct
      oxidation by a metal oxo complex.
AB  - Oxidation of RNA can be effected by two different techniques: a photochemical,
      electron-transfer method termed "flash-quench" and direct oxidation by metal oxo
      complexes. The flash-quench method produces selective oxidation using a metal
      photosensitizer, tris(bipyridyl)ruthenium(III) trichloride (Ru(bpy)(3)(3+)), and
      quencher, pentaamminechlorocobalt(III) chloride (Co(NH(3))(5)Cl(2+)). We have
      optimized the flash-quench technique for the following RNAs: tRNA(Phe), human
      ferritin iron-responsive element (IRE), and a mutated human ferritin IRE. We have
      also employed a chemical footprinting technique involving the oxoruthenium(IV)
      complex (Ru(tpy)(bpy)O(2+) (tpy = 2,2',2''-terpyridine; bpy = 2,2'-bipyridine))
      to oxidize guanine. Comparison of the two methods shows that the flash-quench
      technique provides a visualization of nucleotide accessibility for a static
      conformation of RNA while the Ru(tpy)(bpy)O(2+) complex selectively oxidizes
      labile guanines and gives a visualization of a composite of multiple
      conformations of the RNA structure.

PMID- 20038126
TI  - Self-assembled nanoparticle necklaces network showing single-electron switching
      at room temperature and biogating current by living microorganisms.
AB  - A network of one-dimensional (1D) Au nanoparticle necklaces is synthesized and
      shown to exhibit electronic switching, that is, gating, by the metabolic activity
      of yeast cells deposited on the structure. Without the cells, the network
      exhibits the Coulomb blockade effect at room temperature with a sharp threshold
      voltage, V(T) of approximately 0.45 V, which corresponds to a switching energy of
      approximately 20 kT. Although the enhancement in V(T) from approximately 70 mV
      for a single (10 nm) Au particle to >1 V is well-known for a 2D array, the
      uniqueness of the network topology is the relatively weak dependence of V(T) on
      temperature that leads to room temperature switching behavior, in contrast to an
      array where the blockade effect vanishes at ambient temperatures. The coupling
      between the biochemical process of the cell and the electronics of the network
      has potential applications for making electrodes for biofuel cells and highly
      sensitive biosensors using the cell as the specific sensing moiety.

PMID- 20038125
TI  - Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive
      properties of 3'-(substituted phenyl)epibatidine analogues. Nicotinic partial
      agonists.
AB  - In 1992, John Daly et al. reported the isolation and structure determination of
      epibatidine. Epibatidine's unique structure and its potent nicotinic agonist
      activity have had a tremendous impact on nicotine receptor research. This
      research has led to a better understanding of the nicotinic acetylcholine
      receptor (nAChR) pharmacophore and to epibatidine analogues with potential as
      pharmacotherapies for treating various CNS disorders. In this study, we report
      the synthesis, receptor binding ([(3)H]epibatidine and [(125)I]iodoMLA), and in
      vivo pharmacological properties (mouse tail flick, hot plate, hypothermia, and
      spontaneous activity) of a series of 3'-(substituted phenyl)epibatidine analogues
      (5a-m). Results from these studies have added to the understanding of the nAChR
      pharmacophore and led to nicotinic partial agonists that may have potential for
      smoking cessation. All the analogues had affinities for the alpha4beta2 nAChR
      similar to epibatidine (1). 3'-(3-Dimethylaminophenyl)epibatidine (5m) has a
      nicotinic partial agonist pharmacological profile similar to the smoking
      cessation drug varenicline. Other analogues are partial agonists with varying
      degrees of nicotinic functional agonist and antagonist activity. 3'-(3
      Aminophenyl)epibatidine (5j) is a more potent functional agonist and antagonist
      in all tests than varenicline. 3'-(3-Fluorophenyl)epibatidine and 3'-(3
      chlorophenyl)epibatidine (5c and 5e) are more potent than varenicline when tested
      as agonists in four pharmacological tests and antagonists when evaluated against
      nicotine in the analgesia hot-plate test.

PMID- 20038127
TI  - Cluster-assembled materials: toward nanomaterials with precise control over
      properties.
AB  - One pathway toward nanomaterials with controllable band gaps is to assemble
      solids where atomic clusters serve as building blocks, since the electronic
      structures of clusters vary with size and composition. To study the role of
      organization in cluster assemblies, we synthesized multiple architectures
      incorporating As(7)(3-) clusters through control of the countercations. Optical
      measurements revealed that the band gaps vary from 1.1-2.1 eV, even though the
      assemblies are constructed from the identical cluster building block. Theoretical
      studies explain this variation as being a result of altering the lowest
      unoccupied molecular orbital levels by changing the countercations. Additional
      variations in the gap are made by covalently linking the clusters with species of
      varying electronegativity to alter the degree of charge transfer. These findings
      offer a general protocol for syntheses of nanoassemblies with tunable electronic
      properties.

PMID- 20038128
TI  - Oblongolides from the endophytic fungus Phomopsis sp. BCC 9789.
AB  - Six new oblongolides, W1, W2, X, Y, and Z (1-3, 6, 7) and 2-deoxy-4alpha
      hydroxyoblongolide X (4), and the known compounds oblongolide (8), oblongolides
      T, C, and Q (5, 9, 10), and (-)-5-methylmellein were isolated from the endophytic
      fungus Phomopsis sp. BCC 9789. Compound 7 showed anti-HSV-1 activity (IC50=14
      microM) and cytotoxic activities against KB, BC, NCI-H187, and nonmalignant
      (Vero) cell lines with respective IC50 values of 37, 26, 32, and 60 microM.
      Cytotoxic activity against the BC cell line was also observed for compound 6,
      with an IC50 value of 48 microM.

PMID- 20038129
TI  - Diverging chemoselective reactions of separable amide rotational isomers.
AB  - Diverging chemoselective reactions of a pair of amide rotamers have been observed
      by separating the rotamers and then reacting them individually. Reduction of (Z)
      N-allyl-2-(phenylselanyl)-N-(2,4,6-tri-tert-butylphenyl)acetamide with
      tributyltin hydride at room temperature provides only the product of 5-exo
      cyclization, 4-methyl-1-(2,4,6-tri-tert-butylphenyl)pyrrolidin-2-one. In
      contrast, reduction of the corresponding (E) amide rotational isomer under
      identical conditions provides only the reduced product, (E)-N-allyl-N-(2,4,6-tri
      tert-butylphenyl)acetamide. Such diverging reactions of rotamers may be common in
      transformations involving reactive intermediates (carbenes, radicals,
      organometallic intermediates) that have low barriers to onward reactions relative
      to amide rotation.

PMID- 20038130
TI  - Fully automated continuous flow synthesis of highly functionalized imidazo[1,2-a]
      heterocycles.
AB  - The first continuous flow synthesis of imidazo[1,2-a]pyridine-2-carboxylic acids
      directly from 2-aminopyridines and bromopyruvic acid has been developed,
      representing a significant advance over the corresponding in-flask method. The
      process was applied to the multistep synthesis of imidazo[1,2-a]pyridine-2
      carboxamides, including a Mur ligase inhibitor, using a two microreactor,
      multistep continuous flow process without isolation of intermediates.

PMID- 20038131
TI  - Short access to (+)-lupinine and (+)-epiquinamide via double hydroformylation.
AB  - Short and efficient access to (+)-lupinine and (+)-epiquinamide by means of an
      unprecedented double hydroformylation of a bis-homoallylic azide followed by a
      tandem catalytic hydrogenation/reductive bis-amination is reported.

PMID- 20038132
TI  - Borondipyrromethene dyes with pentane-2,4-dione anchors.
AB  - New, acetylacetone-linked borondipyrromethene (BODIPY) dyes were readily obtained
      from BODIPY cores by various protocols involving direct grafting with
      acetylacetone or cross-coupling from a preorganized phenylacacH derivative
      bearing either an iodo or an ethynyl function. Facile anchoring on TiO(2) powder
      is obtained and scrutinized by FT-IR spectroscopy.

PMID- 20038133
TI  - Synthesis and assignment of absolute configuration of the iridoid 9
      deoxygelsemide.
AB  - The first enantioselective synthesis of 9-deoxygelsemide, belonging to a rare
      group of iridoids isolated from Gelsemium plants, is described. The key synthetic
      steps are a variant of the Woodward-Prevost reaction to install the
      characteristic cis-alpha-1,2-dioxygenated system at C-6 and C-7 with complete
      diastereoselectivity. Construction of the dihydropyran ring was achieved via
      formylation of lactone I, followed by dehydration of the corresponding lactol.
      The synthesis allowed assignment of absolute configuration to 9-deoxygelsemide
      and related iridoids.

PMID- 20038134
TI  - Hydrosulfide (HS-) coordination in iron porphyrinates.
AB  - Recent reports of potential physiological roles of hydrogen sulfide have prompted
      interest in heme-sulfide interactions. Heme-H(2)S and/or heme-HS(-) interactions
      could potentially occur during endogenous production, transport, signaling
      events, and catabolism of H(2)S. We have investigated the interaction of the
      hydrosulfide ion (HS(-)) with iron porphyrinates. UV-vis spectral studies show
      the formation of [Fe(Por)(SH)](-), [Fe(Por)(SH)(2)](2-), and the mixed-ligand
      species [Fe(Por)(Im)(SH)](-). UV-vis binding studies of [Fe(OEP)] and [Fe(T-p
      OMePP)] (OEP = octaethylporphyrinate; T-p-OMePP = tetra-p
      methoxyphenylporphyrinate) with HS(-) allowed for calculation of the formation
      constants and extinction coefficients of mono- and bis-HS(-) complexes. We report
      the synthesis of the first HS(-)-bound iron(II) porphyrin compounds,
      [Na(222)][Fe(OEP)(SH)].0.5C(6)H(6) and [Na(222)][Fe(T-p-OMePP)(SH)].C(6)H(5)Cl
      (222 = Kryptofix-222). Characterization by single-crystal X-ray analysis, mass
      spectrometry, and Mossbauer and IR spectroscopy is all consistent with that of
      known sulfur-bound high-spin iron(II) compounds. The Fe-S distances of 2.3929(5)
      and 2.3887(13) A are longer than all reported values of [Fe(II)(Por)(SR)](-)
      species. An analysis of the porphyrin nonplanarity for these derivatives and for
      all five-coordinate high-spin iron(II) porphyrinate derivatives with an axial
      anion ligand is presented. In our hands, attempts to synthesize iron(III) HS(-)
      derivatives led to iron(II) species.

PMID- 20038135
TI  - Fabrication of crystalline mesoporous metal oxides and sulfides.
AB  - Mesoporous metal oxides and sulfides were prepared by a simple solvothermal
      method using inorganic salts as metal sources and diethylene glycol (DEG) as
      solvent; they are formed by the aggregation of metal compound nanoparticles. The
      generality of this route to the mesoporous materials was proved by the
      fabrication of a series of mesoporous materials (TiO(2), ZrO(2), ZnO, In(2)O(3),
      ZnS, and In(2)S(3)). Due to the different morphologies of nanoparticle subunits,
      the as-prepared mesoporous materials had different types of mesopores, which
      could be revealed by the N(2) adsorption-desorption isotherms and transmission
      electron microscopy (TEM) images.

PMID- 20038136
TI  - Polymer brushes: routes toward mechanosensitive surfaces.
AB  - Soft nanotechnology involves both understanding the behavior of soft matter and
      using these components to build useful nanoscale structures and devices. However,
      molecular scale properties such as Brownian motion, diffusion, surface forces,
      and conformational flexibility dominate the chemistry and physics in soft
      nanotechnology, and therefore the design rules for generating functional
      structures from soft, self-assembled materials are still developing. Biological
      motors illustrate how wet nanoscale machines differ from their macroscopic
      counterparts. These molecular machines convert chemical energy into mechanical
      motion through an isothermal process: chemical reactions generate chemical
      potential and diffusion of ions, leading to conformational changes in proteins
      and the production of mechanical force. Because the actuation steps form a
      thermodynamic cycle that is reversible, the application of mechanical forces can
      also generate a chemical potential. This reverse process of mechanotransduction
      is the underlying sensing and signaling mechanism for a wide range of
      physiological phenomena such as hearing, touch, and growth of bone. Many of the
      biological systems that respond to mechanical stimuli do this via complex stress
      activated ion channels or remodeling of the actin cytoskeleton. These biological
      actuation and mechanosensing processes are rather different from nano- and
      microelectromechanical systems (NEMS and MEMS) produced via semiconductor
      fabrication technologies. In our group, we are working to emulate biological
      mechanotransduction by systematically developing building blocks based on polymer
      brushes. In this soft nanotechnology approach to mechanotransduction, the
      chemical building blocks are polymer chains whose conformational changes and
      actuation can be investigated at a very basic level in polymer brushes,
      particularly polyelectrolyte brushes. Because these polymer brushes are easily
      accessible synthetically with control over parameters such as composition, chain
      length, and chain density, brushes provide a robust platform to study the
      coupling of mechanical forces with conformational changes of the chains. This
      Account provides an overview of our recent research in the design of
      mechanosensitive polymer brushes starting with the demonstration of nanoactuators
      and leading to our first attempts toward the creation of artificial
      mechanotransduction elements. As the brushes collapse in response to external
      triggers such as pH and ion concentration, polyelectrolyte brushes provide
      stimuli-responsive films. These collapse transitions lead to the generation of
      mechanical forces, and by reversing the chain of events, we designed a
      mechanically responsive film with a chemical output. Having reported an initial
      proof-of-principle experiment, we think that the stage is set for the preparation
      of more elaborate mechanosensitive surfaces.

PMID- 20038138
TI  - Mechanistic insight into cell growth, internalization, and cytotoxicity of PAMAM
      dendrimers.
AB  - We report on the role of PAMAM dendrimer concentration and generation (G2, G4,
      G6) on cell growth and cytotoxicity in HEK293T and HeLa cell lines and make
      comparisons with dendrimer-induced leakage from liposomes to probe the mechanisms
      in action. Specifically, we observed a striking transition from cell growth
      enhancement to a reduction in cell viability at a critical PAMAM dendrimer
      concentration, that is, approximately 500 nM. Confocal microscopy studies show
      evidence of a transition from cell membrane adhesion to cell internalization and
      cell nucleus interaction at equivalent dendrimer concentrations. A dendrimer
      concentration window of 500-700 nM was identified for effective cell
      internalization without significant cytotoxicity. Though liposome leakage
      correlated with cytotoxicity, no quantitative agreement was observed, that is,
      cells are 100 times (based on surface coverage) more resistant to dendrimers than
      liposomes. These findings have significant implications in the design of
      effective drug/gene delivery vehicles based on dendrimers.

PMID- 20038137
TI  - Amelogenin nanoparticles in suspension: deviations from spherical shape and pH
      dependent aggregation.
AB  - It is well-known that amelogenin self-assembles to form nanoparticles, usually
      referred to as amelogenin nanospheres, despite the fact that not much is known
      about their actual shape in solution. In the current paper, we combine SAXS and
      DLS to study the three-dimensional shape of the recombinant amelogenins rP172 and
      rM179. Our results show for the first time that amelogenins build oblate
      nanoparticles in suspension using experimental approaches that do not require the
      proteins to be in contact with a support material surface. The SAXS studies give
      evidence for the existence of isolated amelogenin nano-oblates with aspect ratios
      in the range of 0.45-0.5 at pH values higher than pH 7.2 and show an aggregation
      of these nano-oblates at lower pH values. The role of the observed oblate shape
      in the formation of chain-like structures at physiological conditions is
      discussed as a key factor in the biomineralization of dental enamel.

PMID- 20038139
TI  - Syntheses and characterization of a series of silver-thioantimonates(III) and
      thioarsenates(III) containing two types of silver-sulfur chains.
AB  - Three framework silver-thioantimonates, K(3)Ag(9)Sb(4)S(12)(1),
      Rb(3)Ag(9)Sb(4)S(12)(2), and Cs(3)Ag(9)Sb(4)S(12)(3), and one layered silver
      thioarsenate, CsAg(2)AsS(3)(4), have been synthesized solvothermally in the
      presence of thiophenol as a mineralizer. Compounds 1, 2, and 3 are isostructural
      and contain infinite silver-sulfur chains [Ag(9)S(12)](15-). These chains are
      connected to one another by the antimony atoms to generate wide channels along
      the [001] direction where the alkali metal cations reside. The structure of 4
      consists of helical chains [Ag(2)S(3)](4-) linked by the arsenic atoms to form
      layers with potassium ions between the layers.

PMID- 20038140
TI  - Nucleotide- and substrate-induced conformational transitions in the CBS domain
      containing pyrophosphatase of Moorella thermoacetica.
AB  - In contrast to all other known pyrophosphatases, Moorella thermoacetica
      pyrophosphatase (mtCBS-PPase) contains nucleotide-binding CBS domains and is thus
      strongly regulated by adenine nucleotides. Stopped-flow measurements using a
      fluorescent AMP analogue, 2'(3')-O-(N-methylanthranoyl)-AMP (Mant-AMP), reveal
      that nucleotide binding to mtCBS-PPase involves a three-step increase in Mant-AMP
      fluorescence with relaxation times from 0.01 to 100 s, implying conformational
      changes in the complex. This effect is reversed by AMP. Metal cofactors (Co(2+)
      and Mg(2+)) enhance the fluorescence signal but are not absolutely required,
      unlike what is seen when the catalytic reaction is examined. The relaxation times
      and amplitudes of the fluorescence signals depend on Mant-AMP concentration in a
      manner suggestive of the presence of a second binding site for Mant-AMP on the
      protein. Equilibrium fluorescence titration experiments additionally support the
      presence of two types of AMP binding sites with different affinities, whereas
      equilibrium dialysis and membrane filtration measurements reveal binding of one
      AMP molecule per enzyme monomer, implying negative cooperativity in nucleotide
      binding. The substrate (PP(i)) modulates Mant-AMP binding, leading to a further
      conformational change in the enzyme-Mant-AMP complex, and stimulates mtCBS-PPase
      in alkaline medium within a time scale of minutes, via conversion to a more
      active form. This active form initially comprises only a third of the enzyme, as
      estimated from kinetic titration with ADP. AMP inhibits both enzyme forms but is
      unable to independently induce interconversion. Our results collectively suggest
      that nucleotides and the substrate induce multiple conformational changes in
      mtCBS-PPase occurring over a wide time scale; the changes are distinct and almost
      independent.

PMID- 20038141
TI  - Screening libraries to identify proteins with desired binding activities using a
      split-GFP reassembly assay.
AB  - Designer protein modules, which bind specifically to a desired target, have
      numerous potential applications. One approach to creating such proteins is to
      construct and screen libraries. Here we present a detailed description of using a
      split-GFP reassembly assay to screen libraries and identify proteins with novel
      binding properties. Attractive features of the split-GFP based screen are the
      absence of false positives and the simplicity, robustness, and ease of automation
      of the screen. Here, we describe both the construction of a naive protein
      library, and screening of the library using the split-GFP assay to identify
      proteins that bind specifically to chosen peptide sequences.

PMID- 20038142
TI  - Gated molecular recognition and dynamic discrimination of guests.
AB  - Some highly efficient enzymes, e.g., acetylcholinesterase, use gating as a tool
      for controlling the rate by which substrates access their active site to direct
      product formation. Mastering gated molecular encapsulation could therefore be
      important for manipulating reactivity in artificial environments, albeit
      quantitative relationships that describe these processes are unknown. In this
      work, we examined the interdependence between the thermodynamics (DeltaG(o)) and
      the kinetics (DeltaG(in)(double dagger) and DeltaG(out)(double dagger)) of
      encapsulation as mediated by gated molecular basket 1. For a series of isosteric
      guests (2-6, 106-107 A(3)) entering/exiting 1, we found a linear correlation
      between the host-guest affinities (DeltaG(o)) and the free energies of the
      activation (DeltaG(in)(double dagger) and DeltaG(out)(double dagger)), which was
      fit to the following equation: DeltaG(double dagger) = rhoDeltaG(o) + delta.
      Markedly, the kinetics for the entrapment of smaller guest 7 (93 A(3)) and bigger
      guest 8 (121 A(3)) did not follow the free energy trends observed for 2-6. Thus,
      it appears that the kinetics of the gated encapsulation mediated by 1 is a
      function of the encapsulation's favorability (DeltaG(o)) and the guest's profile.
      When the size/shape of guests is kept constant, a linear dependence between the
      encapsulation potential (DeltaG(o)) and the rate of guests' entering/departing
      basket (DeltaG(in/out)(double dagger)) holds. However, when the potential
      (DeltaG(o)) is fixed, the basket discriminates guests on the basis of their
      size/shape via dynamic modulation of the binding site's access.

PMID- 20038143
TI  - Functionalization in flexible porous solids: effects on the pore opening and the
      host-guest interactions.
AB  - The synthesis on the gram scale and characterization of a series of flexible
      functionalized iron terephthalate MIL-53(Fe) type solids are reported. Chemical
      groups of various polarities, hydrophilicities, and acidities (-Cl, -Br, -CF(3), 
      CH(3), -NH(2), -OH, -CO(2)H) were introduced through the aromatic linker, to
      systematically modify the pore surface. X-ray powder diffraction (XRPD),
      molecular simulations, thermogravimetric analyses, and in situ IR and (57)Fe
      Mossbauer spectrometries indicate some similarities with the pristine MIL-53(Fe)
      solid, with the adoption of the narrow pore form for all solids in both the
      hydrated and dry forms. Combined XRPD and computational structure determinations
      allow concluding that the geometry of the pore opening is predominantly
      correlated with the intraframework interactions rather than the steric hindrance
      of the substituent. Only (MIL-53(Fe)-(CF(3))(2)) exhibits a nitrogen accessible
      porosity (S(BET) approximately 100 m(2) g(-1)). The adsorption of some liquids
      leads to pore openings showing some very specific behaviors depending on the
      guest-MIL-53(Fe) framework interactions, which can be related to the energy
      difference between the narrow and large pore forms evaluated by molecular
      simulation.

PMID- 20038144
TI  - Total synthesis of the antimitotic bicyclic peptide celogentin C.
AB  - An account of the total synthesis of celogentin C is presented. A right-to-left
      synthetic approach to this bicyclic octapeptide was unsuccessful due to an
      inability to elaborate derivatives of the right-hand ring. In the course of these
      efforts, it was discovered that the mild Braslau modification of the McFadyen
      Stevens reaction offers a useful method of reducing recalcitrant esters to
      aldehydes. A left-to-right synthetic strategy was then examined. The unusual Leu
      Trp side-chain cross-link present in the left-hand macrocycle was fashioned via a
      three-step sequence comprised of an intermolecular Knoevenagel condensation, a
      radical conjugate addition, and a SmI(2)-mediated nitro reduction. A subsequent
      macrolactamization provided the desired ring system. The high yield and concise
      nature of the left-hand ring synthesis offset the modest diastereoselectivity of
      the radical conjugate addition. Formation of the Trp-His side-chain linkage
      characteristic of the right-hand ring was then accomplished by means of an indole
      imidazole oxidative coupling. Notably, Pro-OBn was required as an additive in
      this reaction. Detailed mechanistic investigations indicated that Pro-OBn
      moderates the concentration of NCS in the reaction mixture, thereby minimizing
      the production of an undesired dichlorinated byproduct. The natural product was
      obtained after macrolactamization and deprotection. The chemical shifts of the
      imidazole hydrogen atoms exhibited significant dependence on temperature,
      concentration, and pH. Antitumor screening indicated that celogentin C inhibits
      the growth of some cancer cell lines.

PMID- 20038145
TI  - Testing and enhancing the in vitro bioaccessibility and bioavailability of
      Rosmarinus officinalis extracts with a high level of antioxidant abietanes.
AB  - An antioxidant-enriched extract (RE) was obtained from rosemary (Rosmarinus
      officinalis) by supercritical fluid extraction to be used as an ingredient to
      design functional foods. The optimized mixture (42 mg RE g(-1) sunflower oil) was
      submitted to in vitro digestion and absorption tests (using Caco2 cells) to
      investigate the effect of these processes on its DPPH scavenging activity and
      also whether its major abietanes (tricyclic diterpenes) might be bioaccessible
      and bioavailable. Results indicated that supplementation of the rosemary extract
      with sunflower oil and lecithin (37 mg g(-1)) enhanced abietanes micellation
      (almost 2-fold). In vitro digestion of the mixture including RE, sunflower oil,
      and lecithin reduced 50% the bioaccesibility in terms of antioxidant activity.
      Bioavailability was 31%. It was evidenced that this activity was not due to the
      original levels of carnosol, carnosic acid, and methyl carnosate (which only 47%
      remained after digestion) but due to their derivatives and digestion products.

PMID- 20038146
TI  - Transient anomalous subdiffusion: effects of specific and nonspecific probe
      binding with actin gels.
AB  - When signaling molecules diffuse through the cytosol, they encounter a wide
      variety of obstacles that hinder their mobility in space and time. Some of those
      factors include, but are not limited to, interactions with mobile and immobile
      targets or obstacles. Besides finding a crowded environment inside the cell,
      macromolecules assemble into molecular complexes that drive specific biological
      functions adding additional complexity to their diffusion. Thus, simple models of
      diffusion often fail to explain mobility through the cell interior, and new
      approaches are needed. Here we used fluorescent correlation spectroscopy to
      measure diffusion of three molecules of similar size with different surface
      properties diffusing in actin gels. The fluorescent probes were (a) quantum dots,
      (b) yellow-green fluorescent spheres, and (c) the beta isoform of Ca(2+)
      calmodulin-dependent protein kinase II tagged with green fluorescent protein. We
      compared various models for fitting the autocorrelation function (ACF) including
      single component, two-component, and anomalous diffusion. The two-component and
      anomalous diffusion models were superior and were largely indistinguishable based
      on a goodness of fit criteria. To better resolve differences between these two
      models, we modified the ACF to observe temporal variations in diffusion. We found
      in both simulated and experimental data a transient anomalous subdiffusion
      between two freely diffusing regimes produced by binding interactions of the
      diffusive tracers with actin gels.

PMID- 20038147
TI  - Stabilization of native and non-native structures by salt bridges in a lattice
      model of the GCN4 leucine dimer.
AB  - We use computer simulations to investigate the influence of salt bridges on the
      dimerization of the GCN4 leucine zipper. Use of a lattice model allows the
      dimerization process to be followed for time scales long enough to investigate
      large-scale structural changes traversing large distances in configuration space.
      We calculated the rate, efficiency, and stability of dimerization and free-energy
      landscapes. We varied the strength of the ionic interactions and find that there
      is an optimal, intermediate salt bridge strength at which the dimerization
      process proceeds at the maximum rate. Though especially strong salt bridge
      strength beneficially stabilizes native dimers if they form, it can also
      stabilize non-native configurations that can hinder the dimerization process. We
      give examples of stable, non-native structures that might arise. These structures
      may be relevant to interesting recent experiments that have provided evidence of
      unusual forms of the leucine zipper GCN4-p1 called the LZ(GCN4) x-forms, which
      dominate the population in certain biochemical conditions.

PMID- 20038148
TI  - Thermal effects on the activity and structural conformation of catechol 2,3
      dioxygenase from Pseudomonas putida SH1.
AB  - A bacterium, Pseudomonas putida SH1, which can catabolize phenol, naphthalene, or
      cresol as the sole carbon and energy source, was isolated from a petroleum
      contaminated site in Taiwan. The catechol 2,3-dioxygenase (C23O) was purified
      from this bacterial strain when grown on naphthalene as the sole carbon and
      energy source. The enzyme is composed of four identical subunits with a native
      molecular weight of 128 +/- 5 kD. Small-angle neutron scattering (SANS)
      techniques were employed to study the thermal effects on the structural
      conformation of this enzyme in solution. The SANS measurements revealed distinct
      changes in the size of the enzyme between 50 and 80 degrees C, and the size was
      not restored during the subsequent cooling. The enzyme started to denature at 55
      degrees C, and the structure was destroyed by the time the temperature reached 80
      degrees C, at which the enzyme had become more than twice the original size. The
      optimal catalytic temperature of the enzyme was at 50 degrees C. The half-life of
      the activity at this temperature was 45 min. The enzyme activity increases
      starting from 25 degrees C and reaches its maximum at 50 degrees C, below which
      no obvious change in the size of the enzyme is found. Noticeable enlargement of
      the enzyme is revealed when the enzymatic activity starts to fall. By combination
      of SANS measurement and biochemical properties of the enzyme, this study
      demonstrates the correlation of enzyme size in solution and catalytic activity
      upon a heat treatment. In addition, for a protein composed of multiple subunits,
      the shape of the enzyme and the dissociation of the enzyme subunits in a thermal
      cycle were also demonstrated by SANS methodology.

PMID- 20038149
TI  - Intermolecular potential energy surface between Ne and NO (2Pir).
AB  - Rotational and rovibrational transitions with parity doublings and hyperfine
      structures of the Ne-NO complex in the electronic ground state have been observed
      by Fourier-transform microwave spectroscopy, and they are analyzed by employing a
      free-rotor model with a standard deviation of the least-squares fit to be 12 kHz.
      A 2-dimensional intermolecular potential energy surface for the Ne-NO complex has
      been determined from the present high-resolution spectroscopic data with the aid
      of high-level ab initio calculations.

PMID- 20038150
TI  - Oxygen optical gas sensing by reversible fluorescence quenching in photo-oxidized
      poly(9,9-dioctylfluorene) thin films.
AB  - We investigated the fluorescence (FL) dependence on the environment oxygen
      content of poly(9,9-dioctylfluorene) (PF8) thin films. We show that the PF8
      interactions with oxygen are not limited to the known irreversible photo
      oxidation, resulting in the formation of Keto defects, but also reversible FL
      quenching is observed. This effect, which is stronger for the Keto defects than
      for the PF8, has been exploited for the realization of a prototype oxygen sensor
      based on FL quenching. The sensing sensitivity of Keto defects is comparable with
      the state of the art organic oxygen sensors based on phosphorescence quenching.

PMID- 20038151
TI  - Magneto-optical biosensing platform based on light scattering from self-assembled
      chains of functionalized rotating magnetic beads.
AB  - We describe a simple protocol for the rapid, highly sensitive, and quantitative
      measurement of the concentration of biomolecules in a solution by monitoring
      light scattered by self-assembled chains of functionalized superparamagnetic
      beads (SBs) rotating in the solution. A rotating external field (H(ex)) applied
      to an aqueous solution containing 250 nm diameter biotinylated SBs produced
      linear chains of SBs rotating in phase with Hex due to magnetically induced self
      assembly. At constant Hex, the addition of avidin to the solution led to the
      formation of longer SB-chains than without the presence of avidin. The generation
      of longer SB-chains was revealed by increases in the amplitude of the oscillating
      optical transmittance signal of the magnetic colloid solution. Monitoring changes
      in the amplitude of the optical transmittance of the solution enabled
      quantitative determination of the concentration of avidin added to the solution
      with a sensitivity of 100 pM (6.7 ng/mL) and a dynamic range of at least 3 orders
      of magnitude. The rotating chains acted as biomolecule probes and micromagnetic
      mixers, enabling detection of biomolecular recognition in less than 30 s. This
      approach offers a rapid, highly sensitive, inexpensive, and homogeneous means for
      detecting biorecognition processes.

PMID- 20038152
TI  - Roaming radical kinetics in the decomposition of acetaldehyde.
AB  - A novel theoretical framework for predicting the branching between roaming and
      bond fission channels in molecular dissociations is described and applied to the
      decomposition of acetaldehyde. This reduced dimensional trajectory (RDT)
      approach, which is motivated by the long-range nature of the roaming, bond
      fission, and abstraction dynamical bottlenecks, involves the propagation of rigid
      body trajectories on an analytic potential energy surface. The analytic potential
      is obtained from fits to large-scale multireference ab initio electronic
      structure calculations. The final potential includes one-dimensional corrections
      from higher-level electronic structure calculations and for the effect of
      conserved mode variations along both the addition and abstraction paths. The
      corrections along the abstraction path play a significant role in the predicted
      branching. Master equation simulations are used to transform the microcanonical
      branching ratios obtained from the RDT simulations to the temperature- and
      pressure-dependent branching ratios observed in thermal decomposition
      experiments. For completeness, a transition-state theory treatment of the
      contributions of the tight transition states for the molecular channels is
      included in the theoretical analyses. The theoretically predicted branching
      between molecules and radicals in the thermal decomposition of acetaldehyde is in
      reasonable agreement with the corresponding shock tube measurement described in
      the companion paper. The prediction for the ratio of the tight to roaming
      contributions to the molecular channel also agrees well with results extracted
      from recent experimental and experimental/theoretical photodissociation studies.

PMID- 20038153
TI  - Excited-state dynamics and two-photon absorption cross sections of fluorescent
      diphenyl-tin(IV) derivatives with schiff bases: a comparative study of the effect
      of chelation from the ultrafast to the steady-state time scale.
AB  - Schiff bases bearing an intramolecular hydrogen bond are known to undergo excited
      state intramolecular proton transfer and E-Z isomerization, which are related to
      their thermochromism and solvatochromism properties. In this study, we explored
      these ultrafast photoinduced processes for two doubly hydroxylated Schiff bases,
      salicylidene-2-aminophenol and 2-hydroxynaphthylmethylidene-2-aminophenol. From
      comparisons with our previously reported results for the parent monohidroxylated
      Schiff base salicylideneaniline, we were able to establish the lack of an effect
      of a second intramolecular hydrogen bond in the excited-state intramolecular
      proton-transfer process. Moreover, we synthesized and studied the photophysics of
      14 diphenyl-tin(IV) derivatives with Schiff bases with the same framework as the
      former two. In these organometallic compounds, we observed an increase of more
      than 50 times in the excited-state decay times in comparison with those of the
      free ligands. This finding is attributed to the coordination with the metallic
      center, which restricts the fluctuations of the geometry of the organic Schiff
      base skeleton. The emission bands of these complexes can be easily tuned through
      substitutions at the Schiff base ligand and can be made to be centered well above
      600 nm. The much enhanced emissive behavior of all diphenyl-tin(IV) derivatives
      allowed the study of several properties of their electronically excited states,
      including the effects of different substituents on their femtosecond and
      picosecond dynamics. Considering potential applications, we also performed
      transient absorption experiments to assess the wavelength interval for stimulated
      emission of this type of compound. Finally, we determined their two-photon
      absorption cross sections in the 760-820-nm range by measuring their two-photon
      induced fluorescence excitation spectra. Mainly, our results illustrate that the
      diphenyl-tin(IV) moiety, thanks to its size and its coordination mode with a
      single Schiff base, can be coordinated to this versatile framework to obtain
      tunable optical properties wherein the emissive states can have lifetimes on the
      nanosecond time scale.

PMID- 20038154
TI  - Structure, dynamics, and power conversion efficiency correlations in a new low
      bandgap polymer: PCBM solar cell.
AB  - Molecular packing structures and photoinduced charge separation dynamics have
      been investigated in a recently developed bulk heterojunction (BHJ) organic
      photovoltaic (OPV) material based on poly(thienothiophene-benzodithiophene)
      (PTB1) with a power conversion efficiency (PCE) of >5% in solar cell devices.
      Grazing incidence X-ray scattering (GIXS) measurements of the PTB1:PCBM ([6,6]
      phenyl-C(61)-butyric acid methyl ester) films revealed pi-stacked polymer
      backbone planes oriented parallel to the substrate surface, in contrast to the pi
      stacked polymer backbone planes oriented perpendicular to the substrate surface
      in regioregular P3HT [poly(3-hexylthiophene)]:PCBM films. A approximately 1.7
      times higher charge mobility in the PTB1:PCBM film relative to that in P3HT:PCBM
      films is attributed to this difference in stacking orientation. The photoinduced
      charge separation (CS) rate in the pristine PTB1:PCBM film is more than twice as
      fast as that in the annealed P3HT:PCBM film. The combination of a small optical
      gap, fast CS rate, and high carrier mobility in the PTB1:PCBM film contributes to
      its relatively high PCE in the solar cells. Contrary to P3HT:PCBM solar cells,
      annealing PTB1:PCBM films reduced the device PCE from 5.24% in the pristine film
      to 1.92% due to reduced interfacial area between the electron donor and the
      acceptor. Consequently, quantum yields of exciton generation and charge
      separation in the annealed film are significantly reduced compared to those in
      the pristine film.

PMID- 20038155
TI  - Molecular dynamics simulations of liquid condensed to liquid expanded transitions
      in DPPC monolayers.
AB  - We have investigated the phase behavior of DPPC (dipalmitoylphosphatidylcholine)
      monolayers at the water-air interface using molecular dynamics simulations, where
      the phospholipids and the water molecules are modeled atomistically. We report
      pressure-area isotherms in the interval of 273-310 K. Our results show evidence
      for a liquid condensed (LC) to liquid expanded (LE) phase transition and indicate
      that ordered condensed phases can nucleate from a starting disordered phase on a
      time scale of approximately 50 ns. The existence of the phase transition is
      confirmed with structural analyses of the phospholipid pair correlation functions
      and of the monolayer thickness. We find that the change in the monolayer
      thickness associated with the LC-LE transition is largely due to a shortening of
      the hydrocarbon chains, with little modification in the average tilt angle of the
      choline head group. This result is compatible with recent sum frequency
      spectroscopy experiments, which concluded that the transition occurs without
      major changes in the orientation of the head group with respect to the monolayer
      plane. The dependence of the simulated pressure-area isotherms on temperature, in
      particular, the reduction in width of the coexistence plateau with increasing
      temperature, is consistent with published experimental pressure-area isotherms.

PMID- 20038156
TI  - Inverse ion mobility spectrometry.
AB  - A novel method is proposed for enhancing the separation power of ion mobility
      spectrometry (IMS) and other similar pulsed techniques, such as time-of-flight
      mass spectrometry. In this technique, rather than generating an ion packet, a dip
      is created in the ion beam. This is achieved by an inverse pulse applied to the
      shutter grid. The dip moves with the same velocity as the ion packet, and the
      detector reads an inverse peak at the same drift time as that of the normal
      operation. Using this technique, we achieved 30-60% higher resolution compared to
      the normal method. In addition, two close peaks that were not resolved via normal
      IMS were well resolved to the baseline using this technique. The main reason for
      the increased resolution is likely the absence of space charge in the dip.

PMID- 20038157
TI  - Reversible reconstructive phase transition of Ba2SnSe5: a new high temperature
      modification with completely different structural motifs.
AB  - A new modification of Ba(2)SnSe(5) was prepared by high temperature synthesis. In
      contrast to its low temperature modification that adopts the orthorhombic space
      group P2(1)2(1)2(1), the new beta-Ba(2)SnSe(5) crystallizes in the monoclinic
      system, space group P2(1)/c, with the lattice parameters a = 9.3949(6) A, b =
      8.8656(6) A, c = 12.5745(7) A, beta = 113.299(4) degrees, V = 961.9(1) A(3), Z =
      4. alpha-Ba(2)SnSe(5) is comprised of Sn(3)Se(10)(8-) units, SnSe(4)(4-)
      tetrahedra, and isolated Se(3)(2-) units, while beta-Ba(2)SnSe(5) contains only
      SnSe(5)(4-) units, wherein Sn is tetrahedrally coordinated by four Se atoms. The
      fifth Se atom is connected to one Se atom of the SnSe(4)(4-) tetrahedron, thereby
      forming a Se(2)(2-) dumbbell. Different band gaps are a result of the different
      structure motifs, which are reflected in different colors of the two Ba(2)SnSe(5)
      modifications, the alpha-form being dark brown and the beta-form being red.

PMID- 20038158
TI  - Biomimetic chemosensor: designing peptide recognition elements for surface
      functionalization of carbon nanotube field effect transistors.
AB  - Single-wall carbon nanotube field effect transistors (SWNT-FETs) are ideal
      candidates for fabricating sensors due to their unique electronic properties and
      have been widely investigated for chemical and biological sensing applications.
      The lack of selectivity of SWNT-FETs has prompted extensive research on
      developing ligands that exhibit specific binding as selective surface coating for
      SWNTs. Herein we describe the rational design of a peptide recognition element
      (PRE) that is capable of noncovalently attaching to SWNTs as well as binding to
      trinitrotoluene (TNT). The PRE contains two domains, a TNT binding domain derived
      from the binding pocket of the honeybee odor binding protein ASP1, and a SWNT
      binding domain previously identified from the phage peptide display library. The
      PRE structure in the presence of SWNT was investigated by performing classical
      all-atom molecular dynamics simulations, circular dichroism spectroscopy, and
      atomic force microscopy. Both computational and experimental analyses demonstrate
      that the peptide retains two functional domains for SWNT and TNT binding. The
      binding motif of the peptide to SWNT and to TNT was revealed from interaction
      energy calculations by molecular dynamics simulations. The potential application
      of the peptide for the detection of TNT is theoretically predicted and
      experimentally validated using a SWNT-FET sensor functionalized with a designer
      PRE. Results from this study demonstrate the creation of chemosensors using
      designed PRE as selective surface coatings for targeted analytes.

PMID- 20038159
TI  - Sesquiterpenes and dimeric sesquiterpenoids from Sarcandra glabra.
AB  - Two new sesquiterpenes, sarcandralactones A (1) and B (2), and five new dimeric
      sesquiterpenoids, sarcandrolides A-E (3-7), along with 10 known compounds were
      isolated from the whole plants of Sarcandra glabra. Their structures were
      elucidated on the basis of spectroscopic analysis. Some of the new isolates
      exhibit significant cytotoxicities when tested against a small panel of tumor
      cell lines.

PMID- 20038160
TI  - Ion specificity at the peptide bond: molecular dynamics simulations of N
      methylacetamide in aqueous salt solutions.
AB  - Affinities of alkali cations and halide anions for the peptide group were
      quantified using molecular dynamics simulations of aqueous solutions of N
      methylacetamide using both nonpolarizable and polarizable force fields. Potassium
      and, more strongly, sodium exhibit an affinity for the carbonyl oxygen of the
      amide group, while none of the halide anions shows any appreciable attraction for
      the amide hydrogen. Heavier halides, however, interact with the hydrophobic
      methyl groups of N-methylacetamide. Using the present results for a model of the
      peptide bond we predict that the destabilizing effect of weakly hydrated
      Hofmeister ions, such as bromide or iodide, is not due to direct interactions
      with the backbone but rather due to attraction to hydrophobic regions of the
      protein.

PMID- 20038161
TI  - Understanding nanoparticle diffusion and exploring interfacial nanorheology using
      molecular dynamics simulations.
AB  - We have studied the dynamics of nanoparticles at polydimethylsiloxane (PDMS) oil
      water interfaces using molecular dynamics (MD) simulations. The diffusion of
      nanoparticles in pure water and low-viscosity PDMS oil is found to be reasonably
      consistent with the prediction by the Stokes-Einstein equation. In addition, we
      have calculated the shear moduli and viscosities of bulk oil and water, as well
      as oil-water interfaces from single nanoparticle tracking and demonstrated the
      potential of probing nanorheology from an MD simulation approach. Surprisingly,
      we found that the lateral diffusion of nanoparticles as well as apparent
      interfacial nanorheology at the PDMS oil (low viscosity)-water interface are
      independent of the position of the nanoparticle at the interface.

PMID- 20038162
TI  - Aggregate breakup in a contracting nozzle.
AB  - The breakup of dense aggregates in an extensional flow was investigated
      experimentally. The flow was realized by pumping the suspension containing the
      aggregates through a contracting nozzle. Variation of the cluster mass
      distribution during the breakage process was measured by small-angle light
      scattering. Because of the large size of primary particles and the dense
      aggregate structure image analysis was used to determine the shape and structure
      of the produced fragments. It was found, that neither aggregate structure,
      characterized by a fractal dimension d(f) = 2.7, nor shape, characterized by an
      average aspect ratio equal to 1.5, was affected by breakage. Several passes
      through the nozzle were required to reach the steady state. This is explained by
      the radial variation of the hydrodynamic stresses at the nozzle entrance,
      characterized through computational fluid dynamics, which implies that only the
      fraction of aggregates whose strength is smaller than the local hydrodynamic
      stress is broken during one pass through the nozzle. Scaling of the steady-state
      aggregate size as a function of the hydrodynamic stress was used to determine the
      aggregate strength.

PMID- 20038163
TI  - Mobilization of colloidal particles by low-frequency dynamic stress stimulation.
AB  - Naturally occurring seismic events and artificially generated low-frequency (1 to
      500 Hz) elastic waves have been observed to alter the production rates of oil and
      water wells, sometimes increasing and sometimes decreasing production, and to
      influence the turbidity of surface and well water. The decreases in production
      are of particular concern, especially when artificially generated elastic waves
      are applied as a method for enhanced oil recovery. The exact conditions that
      result in a decrease in production remain unknown. Although the underlying
      environment is certainly complex, the observed increase in water well turbidity
      after natural seismic events suggests the existence of a mechanism that can
      affect both the subsurface flow paths and the mobilization of in situ colloidal
      particles. This article explores the macroscopic and microscopic effects of low
      frequency dynamic stress stimulations on the release of colloidal particles from
      an analog core representing an infinitesimal section along the propagation paths
      of an elastic wave. Experiments on a column packed with 1 mm borosilicate beads
      and loaded with polystyrene microparticles demonstrate that axial mechanical
      stress oscillations enhance the mobilization of captured microparticles.
      Increasing the amplitude of the oscillations increases the number of
      microparticles released and can also result in cyclical spikes in effluent
      microparticle concentration during stimulation. Under a prolonged period of
      stimulation, the cyclical effluent spikes coincided with fluctuations in the
      column pressure data and continued at a diminished level after stimulation. This
      behavior can be attributed to rearrangements of the beads in the column,
      resulting in possible changes in the void space and/or tortuosity of the packing.
      Optical microscopy observations of the beads during low-frequency oscillations
      reveal that individual beads rotate, thereby rubbing against each other and
      scraping away portions of the adsorbed microparticles. These results support the
      theory that mechanical interactions between porous matrix grains are important
      mechanisms in flow path alteration and the mobilization of naturally occurring
      colloidal particles during elastic wave stimulation. These results also point to
      both continuous and discrete en masse releases of colloidal particles, perhaps
      because of circulation cells within the packing material.

PMID- 20038164
TI  - Thermothickening in solutions of telechelic associating polymers and
      cyclodextrins.
AB  - Telechelic associating polymers (hydrophilic ethoxylated backbone, hydrophobic n
      alkyl end-groups) form viscous solutions in water due to associations between the
      hydrophobes. The addition of alpha-, beta-, or gamma-cyclodextrin (CD)
      substantially reduces the solution viscosity because the CD molecules envelop and
      sequester the hydrophobes in their hydrophobic cavities. The present paper
      explores the variation in polymer-CD solution viscosity with temperature. We find
      that, in the case of alpha-CD alone, the solutions show "thermothickening", i.e.,
      the viscosity increases from 25 to ca. 60 degrees C whereupon it reaches a peak
      value and then drops. In contrast, solutions with beta- and gamma-CD show
      monotonic drops in viscosity upon heating. At a fixed polymer content, the
      thermothickening is higher for higher alpha-CD concentrations. We have also
      studied how surfactants and lipids impact the thermothickening. Addition of
      single-tailed micelle-forming surfactants causes the viscosity to revert to the
      more typical decreasing trend with temperature. However, addition of double
      tailed lipids to a polymer/alpha-CD solution accentuates the thermothickening
      behavior. The thermothickening is explained by the propensity of alpha-CDs to
      unbind from the hydrophobes and form inclusion complexes with the polymer
      backbone as the temperature is raised.

PMID- 20038165
TI  - Dipolar driven spontaneous self assembly of superparamagnetic Co nanoparticles
      into micrometric rice-grain like structures.
AB  - Superparamagnetic single crystal single domain Co nanoparticles of 6 nm in
      diameter evaporated onto highly pyrolytic oriented graphite spontaneously self
      assemble into super structures with an elongated shape. These structures have
      been studied by optical and scanning electron microscopies, atomic and magnetic
      force microscopy, electron dispersive X-ray analysis, and SQUID magnetometry. We
      propose that the weak dipolar interactions between superparamagnetic dipoles of
      the cobalt nanoparticles are responsible for the formation of these structures
      when the dipolar magnetic interactions are strong enough to influence the general
      process of self-assembly dominated by van der Waals forces between neighboring
      nanoparticles and between nanoparticles and the substrate during evaporation of
      the solvent.

PMID- 20038166
TI  - Microconfined shear deformation of a droplet in an equiviscous non-newtonian
      immiscible fluid: experiments and modeling.
AB  - In this work, the microconfined shear deformation of a droplet in an equiviscous
      non-Newtonian immiscible fluid is investigated by modeling and experiments. A
      phenomenological model based on the assumption of ellipsoidal shape and taking
      into account wall effects is proposed for systems made of non-Newtonian second
      order fluids. The model, without any adjustable parameters, is tested by
      comparison with experiments under simple shear flow performed in a sliding plate
      apparatus, where the ratio between the distance between the confining walls and
      the droplet radius can be varied. The agreement between model predictions and
      experimental data is good both in steady state shear and in transient drop
      retraction upon cessation of flow. The results obtained in this work are relevant
      for microfluidics applications where non-Newtonian fluids are used.

PMID- 20038167
TI  - Rheology, microstructure and migration in brownian colloidal suspensions.
AB  - We demonstrate that suspended spherical colloidal particles can be effectively
      modeled as single dissipative particle dynamics (DPD) particles provided that the
      conservative repulsive force is appropriately chosen. The suspension model is
      further improved with a new formulation, which augments standard DPD with
      noncentral dissipative shear forces between particles while preserving angular
      momentum. Using the new DPD formulation we investigate the rheology,
      microstructure and shear-induced migration of a monodisperse suspension of
      colloidal particles in plane shear flows (Couette and Poiseuille). Specifically,
      to achieve a well-dispersed suspension we employ exponential conservative forces
      for the colloid-colloid and colloid-solvent interactions but keep the
      conventional linear force for the solvent-solvent interactions. Our simulations
      yield relative viscosity versus volume fraction predictions in good agreement
      with both experimental data and empirical correlations. We also compute the shear
      dependent viscosity and the first and second normal-stress differences and
      coefficients in both Couette and Poiseuille flow. Simulations near the close
      packingvolume-fraction (64%) at low shear rates demonstrate a transition to flow
      induced string-like structures of colloidal particles simultaneously with a
      transition to a nonlinear Couette velocity profile in agreement with experimental
      observations. After a sufficient increase ofthe shear rate the ordered structure
      melts into disorder with restoration of the linear velocity profile. Migration
      effects simulated in Poiseuille flow compare well with experiments and model
      predictions. The important role of angular momentum and torque in nondilute
      suspensions is also demonstrated when compared with simulations by the standard
      DPD, which omits the angular degrees of freedom. Overall, the new method agrees
      very well with the Stokesian Dynamics method but it seems to have lower
      computational complexity and is applicable to general complex fluids systems.

PMID- 20038168
TI  - Polymer loop formation on a functionalized hard surface: quantitative insight by
      comparison of experimental and Monte Carlo simulation results.
AB  - Polystyrene terminated with carboxylic acid end groups (telechelic polymer) was
      grafted from the melt onto a silicon wafer that contained a monolayer of epoxy
      groups. Ellipsometry and fluorimetry were employed to monitor the kinetics of the
      grafting and loop formation, respectively. These results are quantitatively
      correlated with bond fluctuation Monte Carlo (BFMC) simulations that model the
      grafting and loop formation process. The quantitative correlation found between
      experiment and simulation provides unique insight into the process of polymer
      loop formation. Specifically, this correlation provides a calibration of the
      fluorescence intensity to the amount of singly bound chains present on the
      surface, revealing that about 80% of the bound chains form loops on the surface
      at the longest reaction time studied, and provides the time evolution of singly
      and doubly bound chains during the reaction. Moreover, this correlation is
      broadly applicable and can be used to readily monitor the impact of a broad range
      of reaction conditions (e.g., temperature, telechelic concentration, surface
      density of functional groups) on the loop formation process. This correlation,
      therefore, provides a method to access fundamental information that is not
      accessible by experiment alone and yet is required to tailor surface properties
      through adjusting the coverage and fraction of loops in the grafted layer and to
      correlate surface-sensitive properties to specific grafted layer structure.

PMID- 20038169
TI  - High uptakes of methane in Li-doped 3D covalent organic frameworks.
AB  - By using a multiscale theoretical method, which combines the first-principles
      calculation and grand canonical Monte Carlo (GCMC) simulation, we studied storage
      capacities of methane in 3D covalent organic frameworks (COFs) and their Li-doped
      compounds at T = 243 and 298 K. Our results predicted that, at T = 298 K and 35
      bar, the excess gravimetric capacities of COF-102 and COF-103 reach 17.72 and
      16.61 wt % (corresponding to 302 and 285 cm(3) (STP)/g)), which are in good
      agreement with experimental data, while the excess volumetric capacities of COF
      102 and COF-103 reach 127 and 108 v (STP)/v, respectively. The high methane
      storage capacity of the COFs can be attributed to their ultrahigh surface areas
      and low densities. To further enhance the methane capacity, we investigated the
      impact of Li-doping on the methane storage performance of the COFs. Our first
      principles calculations show that the Li cation doped in the COFs can enhance the
      binding of methane to the substrate significantly because of the London
      dispersion and the induced dipole interaction, due to the strong affinity of Li
      cation to methane molecules. At T = 298 K and relatively low pressures (p < 50
      bar), the Li-doping method nearly doubles the methane uptakes of the COFs,
      compared to the nondoped materials. In particular, at T = 298 K and p = 35 bar,
      the methane volumetric uptakes of Li-doped COF-102 and COF-103 reach 303 and 290
      v (STP)/v, respectively, which is more than 2 times those in the nondoped (127
      and 108 v (STP)/v). To the best of our knowledge, the Li-doped 3D COFs show the
      largest methane storage uptakes at room temperature to date.

PMID- 20038170
TI  - Effect of the incorporation of nitrogen to a carbon matrix on the selectivity and
      capacity for adsorption of dibenzothiophenes from model diesel fuel.
AB  - Two synthetic, polymer-derived carbons were modified with urea to incorporate
      nitrogen surface functional groups. Then they were investigated as adsorbents of
      dibenzothiophene (DBT) and 4, 6-dimethyldibenzothiophene (DMDBT) from simulated
      diesel fuel under dynamic conditions with the total concentration of sulfur being
      20 ppmw. The materials before and after adsorption were characterized using
      elemental analysis, XPS, adsorption of nitrogen, potentiometric titration, and
      thermal analysis. The incorporation of nitrogen species caused a visible increase
      in the adsorption capacity. However, selectivity evaluated on the basis of the
      adsorption of naphthalene decreased. Whereas at low surface coverage the volume
      of pores smaller than 10 A is important, with the progress of adsorption the
      surface chemistry gradually starts to play a more important role via either polar
      or acid/base interactions. The latter are important for the selectivity of
      adsorption when the aromatic hydrocarbons are present. Although polar
      interactions are weaker than the acid-base ones, the centers that they represent
      seem to be more favorable to attract DBT and DMDBT than arenes. There is an
      indication that nitrogen-containing groups contribute to chemical transformations
      of DBT and DMDBT/oxidation and promote the involvement of oxygen from the surface
      groups in the reactive adsorption.

PMID- 20038171
TI  - Salt exclusion in silane-laced epoxy coatings.
AB  - The corrosion protection mechanism of a one-step silane-laced epoxy coating
      system was investigated using neutron reflectivity. Pure epoxy and silane-laced
      epoxy films were examined at equilibrium with saturated NaCl water solution. The
      results demonstrate that the addition of silane introduces a salt-exclusion
      effect to epoxy coating. Specifically, the addition of silane densifies the epoxy
      network, which leads to exclusion of hydrated salt ions by a size effect. The
      effect is particularly significant at the metal-coating interface. Exclusion of
      ions improves the corrosion resistance, particularly for metals susceptible to
      pitting.

PMID- 20038172
TI  - On the shape of surface nanobubbles.
AB  - Previous AFM experiments on surface nanobubbles have suggested an anomalously
      large contact angle theta of the bubbles (typically approximately 160 degrees
      measured through the water) and a possible size dependence theta(R). Here we
      determine theta(R) for nanobubbles on smooth, highly oriented pyrolytic graphite
      (HOPG) with a variety of different cantilevers. It is found that theta(R) is
      constant within experimental error, down to bubbles as small as R = 20 nm, and is
      equal to 119 +/- 4 degrees . This result, which is the lowest contact angle for
      surface nanobubbles found so far, is very reproducible and independent of the
      cantilever type used, provided that the cantilever is clean and the HOPG surface
      is smooth. In contrast, we find that, for a particular set of cantilevers, the
      surface can become relatively rough because of precipitated matter from the
      cantilever onto the substrate, in which case larger nanoscopic contact angles (
      approximately 150 degrees ) show up. In addition, we address the issue of the set
      point dependence. Once the set-point ratio is below roughly 95%, the obtained
      nanobubble shape changes and depends on both nanobubble size and cantilever
      properties (spring constant, material, and shape).

PMID- 20038173
TI  - Electrochemically assisted self-assembly of alkylthiosulfates and alkanethiols on
      gold: the role of gold oxide formation and corrosion.
AB  - Electrochemically directed self-assembly of alkylthiosulfates enables the
      selective formation of monolayers on gold surfaces. These monolayers are
      identical to those formed from the corresponding alkanethiols. However, the
      mechanistic details of monolayer formation under electrochemical conditions as
      well as the role of other variables and residual water in the solvent have not
      been extensively studied. A systematic investigation shows that self-assembly is
      not a result of an outer-sphere one-electron oxidation of alkylthiosulfate.
      Voltammetry and electrochemical quartz crystal microbalance techniques reveal
      that self-assembly involving alkylthiosulfates as well as alkanethiols under
      oxidative conditions proceed through direct reaction with gold oxide and in some
      cases is accompanied by corrosion. X-ray photoelectron spectroscopy indicates
      that monolayers can undergo rapid exchange with molecules in solution under
      electrochemically directed self-assembly conditions.

PMID- 20038174
TI  - Electrochemical desorption of fibrinogen from gold.
AB  - The electrochemically induced desorption of Oregon green labeled fibrinogen
      layers from clean gold surfaces at negative potentials has been probed using
      capacitance, fluorescence microscopy, and atomic force microscopy. Capacitance
      measurements on fibrinogen layers indicate that desorption occurs at potentials
      more negative than -0.8 V and that complete desorption occurs when the electrode
      is biased at -1.2 V. Significantly, the fluorescence intensity initially
      increases as the dye labeled protein is electrochemically desorbed due to a
      decrease in quenching by the gold surface. Following this initial increase, the
      protein diffuses into solution and the fluorescence intensity decreases over
      time. More than 90% of the dye labeled fibrinogen is desorbed and diffuses out of
      the confocal volume in less than 2000 s when the potential is stepped to -1.2 V.
      AFM before and after application of the desorbing potential confirms removal of
      the protein. Collection of the desorbed protein in solution reveals a surface
      coverage of (4.0 +/- 2.3) x 10(-13) mol cm(-2) or an area of occupation of 400 +/
      140 nm(2) per molecule, which indicates that the protein is not extensively
      spread on the bare gold surface. Significantly, SDS-PAGE analysis indicates that
      the adsorption-desorption cycle dramatically effects the protein structure, with
      the electrochemically desorbed fibrinogen showing extensive fragmentation
      compared to native protein.

PMID- 20038175
TI  - Molecular rearrangement of metal-chelating lipid monolayers upon protein
      adsorption.
AB  - The controlled adsorption of proteins to well-defined monolayers is critical to
      advances in sensor and nanotechnology applications where selective adsorption of
      targeted species is of interest. In the studies reported here, we developed
      vibrational spectroscopic methods to gain molecular insight into the effect of
      single-site versus multiple-site binding of proteins to metal-chelating
      monolayers at an air-water interface. Analysis of real-time planar array infrared
      reflection-absorption spectra revealed that a Cu(II)-chelated DSIDA lipid
      monolayer (Cu(2+)-DSIDA) was readily disrupted by adsorption of myoglobin as
      demonstrated by a blue shift of 1.7 cm(-1) in the v(as)(CH(2)) stretching mode
      and a reduced peak intensity over a period of 5 h. However, a Zn(II)-chelated
      monolayer was not affected by the adsorption of either protein, suggesting that
      multisite binding of protein on the Cu(2+)-DSIDA results in monolayer disruption.
      Further studies demonstrated that in film form, adsorption of myoglobin to the
      Cu(2+)-DSIDA perturbed the secondary structures of myoglobin, especially the
      alpha-helical, random structure, and extended structures. However, no distinct
      change was observed during adsorption of lysozyme. These results demonstrate the
      utility of these methods for monitoring the molecular rearrangement of both metal
      charged lipid monolayers and proteins that occur during adsorption of a protein
      with a strong affinity for the monolayer.

PMID- 20038176
TI  - Surface modification changes the degradation process and degradation product
      pattern of polylactide.
AB  - The effect of surface modification on the degradation process and degradation
      product patterns of degradable polymers is still a basically unexplored area even
      though a significant effect can be expected. Polylactide (PLA) and PLA grafted
      with acrylic acid (PLA-AA) were, thus, subjected to hydrolytic degradation, and
      water-soluble degradation products were determined by electrospray ionization
      mass spectrometry (ESI-MS) after different time periods. Low molar mass compounds
      migrated from surface-grafted PLA already during the first 7 days at 37 degrees
      C, while it took 133 days in the case of nongrafted PLA before any low molar mass
      compounds were detected in the aging water. In addition, the degradation product
      pattern of surface-grafted PLA showed significant variation as a function of
      hydrolysis time with the evolution of short and long AA-grafted lactic acid
      oligomers as well as plain lactic acid oligomers after different time periods.
      The degradation product pattern of plain PLA consisted of lactic acid and its
      oligomers with up to 13 lactic acid units. Surface grafting, thus, changed the
      degradation product patterns and accelerated the formation of water-soluble
      degradation products.

PMID- 20038177
TI  - Controlling DNA adsorption and diffusion on lipid bilayers by the formation of
      lipid domains.
AB  - We describe the influence of membrane heterogeneity on the adsorption and
      diffusion of DNA. Cellular membranes are believed to contain domains (lipid
      rafts) that influence processes ranging from signal transduction to the diffusion
      of membrane components. By analogy, we demonstrate that the formation of raft
      like domains in supported lipid bilayers provides control over the adsorption and
      diffusion of DNA. The formation of bilayers from a mixture of the gel phase
      zwitterionic lipid 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC) and the
      fluid phase cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)
      yielded coexisting DSPC-enriched and DOTAP-enriched phases. We demonstrated the
      ability to pattern the adsorption of DNA on the heterogeneous bilayers, with the
      adsorption being restricted to the DOTAP-enriched phase. We further demonstrated
      that the DSPC-enriched domains acted as obstacles to the lateral diffusion of
      adsorbed DNA. Fluorescence recovery after photobleaching (FRAP) analysis revealed
      that the diffusivity of the adsorbed DNA tracked that of the underlying lipid,
      although the lipid diffusivity changed by an order of magnitude with changes in
      bilayer composition. Fundamental insight into the adsorption and diffusion of DNA
      on heterogeneous surfaces may be useful for the design of novel techniques for
      the size-based separation of DNA.

PMID- 20038179
TI  - Self-assembled TiO(2) nanotube arrays by anodization of titanium in diethylene
      glycol: approach to extended pore widening.
AB  - We report on the formation of titanium dioxide nanotube arrays having the largest
      known pore size, approximately 350 nm diameter. The nanotube arrays are
      synthesized by Ti foil anodization in a diethylene glycol electrolyte containing
      low (0.5-2%) concentrations of hydrofluoric acid. The large pore size nanotube
      arrays are achieved with extended anodization durations of approximately 120 h,
      with the anodization duration showing a more significant effect on pore diameter
      than the anodization voltage. It appears that the combined effects of
      hydrofluoric acid content and anodization duration determine the lateral etching
      rate of the nanotubes, leading to the larger pore size nanotubes.

PMID- 20038178
TI  - Gaseous adsorption in melanins: hydrophilic biomacromolecules with high
      electrical conductivities.
AB  - The melanins are an important class of multifunctional biomacromolecules that
      possess a number of intriguing physical and chemical properties including
      electrical and photoconductivity. Unusually for a conducting organic material,
      eumelanin is hydrophilic and its electrical properties are strongly dependent on
      its hydration state. We have therefore measured adsorption isotherms for two
      polar adsorbates, water and ethanol, in the pressed powder pellets of synthetic
      eumelanin typically used in electrical studies. We show that a simple kinetic
      monolayer Langmuir model describes the adsorption and find that there are strong
      adsorbate-eumelanin interactions in both cases. These isotherms allow the proper
      scaling of electrical conductivity data and in doing so make progress toward a
      better understanding of eumelanin electrical properties, which is a critical
      prerequisite to the design of new eumelanin-like bioelectronic materials.

PMID- 20038180
TI  - Galvanic deposition of Pt clusters on silicon: effect of HF concentration and
      application as catalyst for silicon nanowire growth.
AB  - We report on the galvanic deposition of Pt on Si from solutions containing
      PtCl(2) and different concentrations of HF. The results show that for low
      [HF]/[Pt] ratios (<or=26), only a thin layer of PtSi is formed. The deposition
      rate of Pt increases with [HF] in the plating solution, up to [HF]/[Pt]
      approximately 530; after this ratio, the morphology of the Pt film changes:
      larger clusters are formed, which cover the Si substrate less densely. Detailed
      atomic force microscopy and X-ray photoelectron spectroscopy analyses show that
      the deposited Pt layers do not completely cover the Si substrate. The Pt and PtSi
      films formed are able to catalyze the formation of Si nanowires (Si NWs) arrays
      formed via vapor-liquid-solid (VLS) process. By changing the immersion time in
      the Pt plating solution, Si NWs arrays with different density, diameter, and
      orientation are obtained.

PMID- 20038181
TI  - A bioinspired wet/dry microfluidic adhesive for aqueous environments.
AB  - A pressure-sensitive, nonreacting and nonfouling adhesive which can perform well
      both in air and underwater is very desirable because of its potential
      applications in various settings such as biomedical, marine, and automobile.
      Taking a clue from nature that many natural adhesive pads have complex structures
      underneath the outer adhesive layer, we have prepared thin elastic adhesive films
      with subsurface microstructures using PDMS (poly(dimethylsiloxane)) and
      investigated their performance underwater. The presence of embedded structure
      enhances the energy of adhesion considerably both in air and underwater.
      Furthermore, filling the channels with liquid of suitable surface tension
      modifies the internal stress profile, resulting into significant enhancement in
      adhesive performance. As this increase in adhesion is mediated by mechanics and
      not by surface chemistry, the presence of water does not alter its performance
      much. For the same reason, this adhesion mechanism works with both hydrophobic
      and hydrophilic surfaces. The adhesive can be reused because of its elastic
      surface. Moreover, unlike many other present-day adhesives, its performance does
      not decrease with time.

PMID- 20038182
TI  - Comparison of dye photodegradation and its coupling with light-to-electricity
      conversion over TiO(2) and ZnO.
AB  - Through comparing the photocatalytic performance of microscale ZnO, nano ZnO, and
      Degussa P25 titania (P25), it was found that the microscale ZnO exhibited 2.6
      35.7 times higher photocatalytic activity for the photodegradation of various dye
      pollutants than P25 under both UV-visible and visible irradiation and showed much
      better photostability than the nano ZnO. The photocatalysts were characterized
      with XRD, Raman, BET, DRUV-vis, adsorption of dye, photoelectrochemical
      measurement, and PL. The much higher photocataltyic activity of the microscale
      ZnO than P25 under UV-visible irradiation is attributed to the higher efficiency
      of generation, mobility, and separation of photoinduced electrons and holes. The
      much higher visible photocataltyic activity of the microscale ZnO than P25 is due
      to the higher photosensitization efficiency of electron transfer from an excited
      dye to the conduction band of the microscale ZnO than that of P25. The much
      better photostability of the microscale ZnO than the nano ZnO is due to its
      better crystallinity and lower defects. The photostability of the microscale ZnO
      is greatly improved by the surface modification of ZnO with a small amount of
      TiO(2). On the basis of the excellent photocatalytic performance of the
      microscale ZnO and TiO(2)-modified ZnO, a novel device of coupling
      photodegradation with light-to-electricity conversion was developed, which is a
      promising candidate for the photocatalytic removal of dye pollutants and a
      renewable energy source.

PMID- 20038183
TI  - Characterization of the liver tissue interstitial fluid (TIF) proteome indicates
      potential for application in liver disease biomarker discovery.
AB  - Tissue interstitial fluid (TIF) forms the interface between circulating body
      fluids and intracellular fluid. Pathological alterations of liver cells could be
      reflected in TIF, making it a promising source of liver disease biomarkers. Mouse
      liver TIF was extracted, separated by SDS-PAGE, analyzed by linear ion trap mass
      spectrometer, and 1450 proteins were identified. These proteins may be secreted,
      shed from membrane vesicles, or represent cellular breakdown products. They show
      different profiling patterns, quantities, and possibly modification/cleavage of
      intracellular proteins. The high solubility and even distribution of liver TIF
      supports its suitability for proteome analysis. Comparison of mouse liver TIF
      data with liver tissue and plasma proteome data identified major proteins that
      might be released from liver to plasma and serve as blood biomarkers of liver
      origin. This result was partially supported by comparison of human liver TIF data
      with human liver and plasma proteome data. Paired TIFs from tumor and nontumor
      liver tissues of a hepatocellular carcinoma patient were analyzed and the profile
      of subtracted differential proteins supports the potential for biomarker
      discovery in TIF. This study is the first analysis of the liver TIF proteome and
      provides a foundation for further application of TIF in liver disease biomarker
      discovery.

PMID- 20038184
TI  - Identification of sortase A (SrtA) substrates in Streptococcus uberis: evidence
      for an additional hexapeptide (LPXXXD) sorting motif.
AB  - Sortase (a transamidase) has been shown to be responsible for the covalent
      attachment of proteins to the bacterial cell wall. Anchoring is effected on
      secreted proteins containing a specific cell wall motif toward their C-terminus;
      that for sortase A (SrtA) in Gram-positive bacteria often incorporates the
      sequence LPXTG. Such surface proteins are often characterized as virulence
      determinants and play important roles during the establishment and persistence of
      infection. Intramammary infection with Streptococcus uberis is a common cause of
      bovine mastitis, which impacts on animal health and welfare and the economics of
      milk production. Comparison of stringently produced cell wall fractions from S.
      uberis and an isogenic mutant strain lacking SrtA permitted identification of 9
      proteins likely to be covalently anchored at the cell surface. Analysis of these
      sequences implied the presence of two anchoring motifs for S. uberis, the
      classical LPXTG motif and an additional LPXXXD motif.

PMID- 20038185
TI  - Chemical basis of nitrogen recovery through the ureide pathway: formation and
      hydrolysis of S-ureidoglycine in plants and bacteria.
AB  - While some organisms, including humans, eliminate oxidized purines to get rid of
      excess nitrogen, for many others the recovery of the purine ring nitrogen is
      vital. In the so-called ureide pathway, nitrogen is released as ammonia from
      allantoate through a series of reactions starting with allantoate amidohydrolase
      (AAH), a manganese-dependent enzyme found in plants and bacteria. We report NMR
      evidence that the true product of the AAH reaction is S-ureidoglycine, a
      nonstandard alpha-amino acid that spontaneously releases ammonia in vitro. Using
      gene proximity and logical genome analysis, we identified a candidate gene (ylbA)
      for S-ureidoglycine metabolism. The proteins encoded by Escherichia coli and
      Arabidopsis thaliana genes catalyze the manganese-dependent release of ammonia
      through hydrolysis of S-ureidoglycine. Hydrolysis then inverts the configuration
      and yields S-ureidoglycolate. S-Ureidoglycine aminohydrolase (UGHY) is cytosolic
      in bacteria, whereas in plants it is localized, like allantoate amidohydrolase,
      in the endoplasmic reticulum. These findings strengthen the basis for the known
      sensitivity of the ureide pathway to Mn availability and suggest a further
      rationale for the active transport of Mn in the endoplasmic reticulum of plant
      cells.

PMID- 20038186
TI  - 2D depiction of fragment hierarchies.
AB  - Drug discovery projects often involve organizing compounds in the form of a
      hierarchical tree, where each node is a substructure fragment shared by all of
      its descendent nodes. A method is described for producing 2D depiction layout
      coordinates for each of the nodes in such a tree, ensuring that common fragments
      within molecular structures are drawn in an identical way, and arranged with a
      consistent orientation. This is achieved by first deriving a common numbering
      scheme for common fragments, then using this scheme to redepict each of the
      molecules, one fragment at a time, so that common fragments have common depiction
      motifs. Once complete, the distinct root branches can be overlaid onto each
      other, after which all of the fragments and whole molecules have a common layout
      and orientation. Several methods are described for preparing visual
      representations of molecular structure hierarchies alongside activity
      information. Combining high level tree display and structure depiction showing
      common features readily facilitates insight into structure-activity
      relationships.

PMID- 20038187
TI  - Radiation chemical studies of methionine in aqueous solution: understanding the
      role of molecular oxygen.
AB  - The oxidation of methionine is an important reaction in the biological milieu.
      Despite a few decades of intense studies, several fundamental aspects remain to
      be defined. We have investigated in detail the gamma-radiolysis of free
      methionine in the absence and presence of molecular oxygen followed by product
      characterization and quantification. The primary site of attack by HO(*) radicals
      and H(*) atoms is the sulfur atom of methionine. We have disclosed that HO(*)
      radicals do not oxidize methionine to the corresponding sulfoxide in either the
      presence or the absence of oxygen; the oxidizing species is H(2)O(2) derived
      either from the radiolysis of water or from the disproportionation of the
      byproduct O(2)(*-). 3-Methylthiopropionaldehyde is the major product of HO(*)
      radical attack in the presence of molecular oxygen. Together with the direct
      oxidation at sulfur as the major product, the potential of H(*) atoms is also
      proven to be highly specific for sulfur atom attack under anoxic and aerobic
      conditions. The major products derived from the H(*) atoms attack are found to be
      alpha-aminobutyric acid or homoserine, in the absence or presence of oxygen,
      respectively. All together, these results help clarify the fate of methionine
      related to a biological environment and offer a molecular basis for envisaging
      other possible pathways of in vivo degradation as well as other markers.

PMID- 20038188
TI  - Combining machine learning and pharmacophore-based interaction fingerprint for in
      silico screening.
AB  - In this study, we developed a new pharmacophore-based interaction fingerprint
      (Pharm-IF) and examined its usefulness for in silico screening using machine
      learning techniques such as support vector machine (SVM) and random forest (RF)
      instead of similarity-based ranking. Using the docking results of PKA, SRC,
      cathepsin K, carbonic anhydrase II, and HIV-1 protease, the screening
      efficiencies of the Pharm-IF models were compared to GLIDE score and the residue
      based IF (PLIF) models. The combination of SVM and Pharm-IF demonstrated a higher
      enrichment factor at 10% (5.7 on average) than those of GLIDE score (4.2) and
      PLIF (4.3). In terms of the size of the training sets, learning more than five
      crystal structures enabled the machine learning models to stably achieve better
      efficiencies than GLIDE score. We also employed the docking poses of known active
      compounds, in addition to the crystal structures, as positive samples of training
      sets. The enrichment factors of the RF models at 10% using the docking poses for
      SRC and cathepsin K showed significantly higher values (6.5 and 6.3) than those
      using only the crystal structures (3.9 and 3.2), respectively.

PMID- 20038189
TI  - Considering the value associated with innovation in health technology appraisal
      decisions (deliberations): a NICE thing to do?

PMID- 20038190
TI  - Ongoing pharmaceutical reforms in France: implications for key stakeholder
      groups.
AB  - The rapid rise in pharmaceutical costs in France has been driven by new
      technologies and the growing prevalence of chronic diseases as well as
      considerable prescribing freedom and choice of physician among patients. This has
      led to the introduction of a number of reforms and initiatives in an attempt to
      moderate expenditure whilst ensuring universal coverage and rewarding innovation.
      These reforms include accelerating access to and granting average European prices
      for new innovative drugs, delisting drugs where there are concerns over their
      value and instigating rebates for excessive prescribing. Alongside this, ongoing
      initiatives to improve the quality and efficiency of prescribing include
      programmes to enhance generic prescribing and dispensing as well as to reduce
      antibacterial and anxiolytic/hypnotic prescribing. However, there have been few
      publications documenting the impact of specific reforms on the overall costs and
      quality of care, which have been exacerbated by compartmentalization of budgets.
      Estimates suggest savings of over 27 million euro/year by decreasing
      antibacterial prescribing, 450 million euro/year by not reimbursing ineffective
      drugs, 670 million euro/year from pharmaceutical company rebates and
      approximately 1 billion euro/year from increased prescribing and dispensing of
      generics (year 2003-7 values). Additional savings of at least 1.5 billion
      euro/year are seen as being possible from increased use of generics such as
      generic proton pump inhibitors, statins (HMG-CoA reductase inhibitors) and ACE
      inhibitors instead of current branded products such as angiotensin II type 1
      receptor antagonists (angiotensin receptor blockers [ARBs]). Delisting drugs when
      there are concerns about their value provides an example to other countries with
      currently limited demand-side measures. Other possible examples include price :
      volume agreements and multifaceted campaigns to enhance generic prescribing and
      dispensing and reduce antibacterial prescribing. Possible future initiatives
      could include adopting more stringent criteria for categorizing new drugs as
      innovative as well as further reductions in the prices of generics. Other
      initiatives could include further enhancement of the quality and efficiency of
      prescribing, including formal auditing of physician prescribing, as well as
      increasing efforts to monitor the risk : benefit ratio of new drugs post-launch
      in real-world practice.

PMID- 20038191
TI  - Is the societal approach wide enough to include relatives? Incorporating
      relatives' costs and effects in a cost-effectiveness analysis.
AB  - It is important for economic evaluations in healthcare to cover all relevant
      information. However, many existing evaluations fall short of this goal, as they
      fail to include all the costs and effects for the relatives of a disabled or sick
      individual. The objective of this study was to analyse how relatives' costs and
      effects could be measured, valued and incorporated into a cost-effectiveness
      analysis. In this article, we discuss the theories underlying cost-effectiveness
      analyses in the healthcare arena; the general conclusion is that it is hard to
      find theoretical arguments for excluding relatives' costs and effects if a
      societal perspective is used. We argue that the cost of informal care should be
      calculated according to the opportunity cost method. To capture relatives'
      effects, we construct a new term, the R-QALY weight, which is defined as the
      effect on relatives' QALY weight of being related to a disabled or sick
      individual. We examine methods for measuring, valuing and incorporating the R
      QALY weights. One suggested method is to estimate R-QALYs and incorporate them
      together with the patient's QALY in the analysis. However, there is no well
      established method as yet that can create R-QALY weights. One difficulty with
      measuring R-QALY weights using existing instruments is that these instruments are
      rarely focused on relative-related aspects. Even if generic quality-of-life
      instruments do cover some aspects relevant to relatives and caregivers, they may
      miss important aspects and potential altruistic preferences. A further
      development and validation of the existing caregiving instruments used for
      eliciting utility weights would therefore be beneficial for this area, as would
      further studies on the use of time trade-off or Standard Gamble methods for
      valuing R-QALY weights. Another potential method is to use the contingent
      valuation method to find a monetary value for all the relatives' costs and
      effects. Because cost-effectiveness analyses are used for decision making, and
      this is often achieved by comparing different cost-effectiveness ratios, we argue
      that it is important to find ways of incorporating all relatives' costs and
      effects into the analysis. This may not be necessary for every analysis of every
      intervention, but for treatments where relatives' costs and effects are
      substantial there may be some associated influence on the cost-effectiveness
      ratio.

PMID- 20038192
TI  - Analytical strategies for characterizing chemotherapy diffusion with patient
      level population-based data.
AB  - To inform assessments of the quality of cancer care, we describe analytical
      approaches to characterizing trends in diffusion of chemotherapy drugs subsequent
      to their US FDA approval. The economics and medical literature provide two
      distinct sets of empirical methods for investigating diffusion of innovations:
      aggregate models, which use the level of market penetration as an estimator of
      diffusion; and disaggregate models, which evaluate diffusion based on the time
      required for different individual units to adopt innovations. When patient-level
      population-based data are available, disaggregate methods make the best use of
      the available information. We propose a method that employs time-to-event
      techniques to describe the probability of utilization of a drug within a
      specified timeframe subsequent to the diagnosis of cancer. By mapping the
      relationship between this probability and calendar time of a patient's diagnosis,
      we can assess trends in diffusion. Our approach accounts for the dependent
      censoring for death, as well as for the clustering of patients within physicians.
      The method proposed is illustrated using Surveillance, Epidemiology, and End
      Results (SEER)-Medicare data applied to two case studies: gemcitabine, approved
      for stage III/IV pancreatic cancer; and irinotecan, approved as a second-line
      therapy for stage IV colorectal cancer.

PMID- 20038193
TI  - Inpatient costs of endophthalmitis evaluated for the whole of France.
AB  - BACKGROUND: Endophthalmitis is a severe condition that requires hospitalization
      with at least day care. Information on the incidence rate, costs and consequences
      of endophthalmitis is scarce. OBJECTIVE: To estimate the number of patients with
      endophthalmitis hospitalized in France, as well as the average costs and hospital
      budget consequences. METHODS: French Programme de Medicalisation des Systemes
      d'Information (PMSI) data for 2006, derived from the official DRG classification,
      were analysed. Data were extracted concerning the following primary diagnoses:
      'purulent endophthalmitis', 'other endophthalmitis' and 'endophthalmitis
      associated with another disease'. Two durations of hospitalization were compared:
      the actual duration and a weighted DRG duration. The cost of hospitalization was
      weighted by the average DRG cost + daily hospital costs x the difference between
      the actual and weighted DRG days in hospital. All costs are presented in euro,
      year 2007 values. RESULTS: A total of 1518 patients (mean age 68.7 years; 47.1%
      male) experienced 1725 hospitalizations for endophthalmitis, including 1416 cases
      (82.1%) admitted to public hospitals. The majority of patients (79.1%) were
      classified by DRG codes that did not specify endophthalmitis (DRG 02M03Z). Most
      patients (1342) were given a drug injection and 510 underwent vitrectomy. Four
      patients died in hospital and 75 were transferred to other hospitals. The actual
      duration of hospitalization for endophthalmitis in public hospitals was 8.1 days
      (mean), whereas the average weighted DRG duration was 5.1 days, which
      underestimated the actual duration by 3 days. The average hospital cost was 3688
      euro per patient, totalling 6,361,119 euro per annum for all public and private
      hospitalizations in France, including 223,723 euro as day care. If hospital
      funding was wholly based on DRG tariffs, the budget for endophthalmitis would be
      severely underestimated. The DRG inclusion of 'severe acute ocular infections' as
      a proxy for endophthalmitis dramatically underestimated its true cost by
      approximately 30%. CONCLUSION: For health economic evaluations, it is
      inappropriate to use DRG classifications as proxies for endophthalmitis.
      Expressed more generally, hospitalization cost analyses should not be based on
      any specific DRG, but always on the clinically relevant primary diagnosis. The
      PMSI clustering algorithm underestimates the hospital budgets required for
      endophthalmitis. Lastly, the PMSI (exhaustively reporting all hospitalizations)
      is best suited to capturing yearly endophthalmitis incidence rates, average costs
      and national health expenditure.

PMID- 20038194
TI  - Healthcare costs in renal transplant recipients using branded versus generic
      ciclosporin.
AB  - BACKGROUND: Generic ciclosporin A modified (CsA) does not have an equivalent
      pharmacokinetic profile to branded CsA in some transplant populations,
      potentially leading to negative clinical consequences and increased long-term
      costs. OBJECTIVE: To assess direct healthcare costs for de novo renal transplant
      recipients in the US receiving branded versus generic CsA in the first month
      after transplantation. METHODS: Administrative claims data from eight private US
      health plans were linked to the Organ Procurement and Transplantation Network
      data. A total of 227 renal transplant cases between 1996 and 2004 were included:
      183 were dispensed branded CsA and 44 received generic CsA. Log transformed
      multiple linear regression was used to model total first-year healthcare costs
      after the initial CsA claim, controlling for both patient demographics and
      clinical characteristics and clustering at the transplant centre level. RESULTS:
      After controlling for patient factors and pre-CsA costs, total healthcare costs
      were significantly higher (p = 0.04) for patients receiving generic CsA versus
      branded CsA. The main driver for the difference was the cost associated with
      immunosuppressants other than CsA (p = 0.01). CONCLUSION: Despite initial
      perceived cost savings associated with generic CsA, de novo renal transplant
      recipients incurred greater total healthcare costs than those treated with
      branded CsA. Patients receiving generic CsA may need higher doses or other
      immunosuppressants to maintain the transplanted kidney than patients receiving
      branded CsA. Providers and payers need to be aware of potential differences in
      total healthcare costs between formulations of bioequivalent critical-dose drugs
      to make the best choice for patient care.

PMID- 20038195
TI  - Separation of the perivascular basement membrane provides a conduit for
      inflammatory cells in a mouse spinal cord injury model.
AB  - Spinal cord injury results in disruption of the cord microstructure, which is
      followed by inflammation leading to additional deterioration. Perivascular
      basement membranes are a component of the spinal cord microstructure that lies
      between blood vessels and astrocytes. The impact of disrupting the basement
      membrane structure on the expansion of inflammation has not been fully examined.
      The objective of this study was to clarify the relationship between damage to
      basement membranes and inflammation after spinal cord injury. Immunohistochemical
      analyses of the perivascular extracellular matrix were performed in a mouse
      spinal cord injury model. In normal tissue, the perivascular basement membrane
      was a single-layer structure produced by both endothelial cells and surrounding
      astrocytes. After spinal cord injury, however, the perivascular basement membrane
      often separated into an inner endothelial basement membrane and an outer
      parenchymal basement membrane. The altered basement membranes formed during the
      acute phase (within 7 days after spinal cord injury). During the subacute phase
      of injury, numerous monocytes and macrophages accumulated in the space between
      the separated basement membranes and infiltrated into the parenchyma where
      astrocytic endfeet were displaced. Infiltration of inflammatory cells from the
      injury core was attenuated coincident with the appearance of the glia limitans
      and glial scar. Furthermore, the outer parenchymal basement membrane was
      connected to the basement membrane of the glia limitans surrounding the injury
      core. Our data suggest that structurally altered basement membranes facilitate
      expansion of secondary inflammation during the subacute phase of spinal cord
      injury.

PMID- 20038196
TI  - Activation of interferon response through toll-like receptor 3 impacts viral
      pathogenesis and pulmonary toll-like receptor expression during respiratory
      syncytial virus and influenza infections in the cotton rat Sigmodon hispidus
      model.
AB  - Interferon (IFN) therapy in humans often causes flu-like symptoms by an unknown
      mechanism. Poly ICLC is a synthetic dsRNA and a Toll-like receptor 3 (TLR3)
      agonist with a strong IFN-inducing ability. In this work, we analyzed the effect
      of poly ICLC on pulmonary responses to influenza and respiratory syncytial virus
      (RSV) infections in the cotton rat (Sigmodon hispidus) model. Viral replication,
      pulmonary inflammation, and expression of IFN, TLR, and chemokines were monitored
      and compared. Antiviral effect of poly ICLC against influenza virus and RSV was
      best achieved at high poly ICLC concentrations that, in the absence of virus
      infection, induced a strong IFN response. The antiviral doses of poly ICLC,
      however, also increased lung inflammation, an unexpected finding because of the
      reported poly ICLC safety in BALB/c mice. Similarly, in contrast to murine model,
      pathology of RSV infection was increased in cotton rats treated with poly ICLC.
      Augmented lung inflammation was accompanied by an earlier induction of IFN and
      TLR responses and a stronger chemokine expression. Overall, these findings
      indicate significant association between antiviral IFN action and pulmonary
      inflammation and highlight important animal model-specific variations in the
      potential of IFN to cause pathology.

PMID- 20038197
TI  - STAT-phosphorylation-independent induction of interferon regulatory factor-9 by
      interferon-beta.
AB  - Type I interferon (IFN)-dependent STAT1 and STAT2 activation requires specific
      tyrosine residues (337Y and 512Y) located in the cytoplasmic domain of IFNAR-2c,
      the beta-subunit of the human type I IFN receptor. To identify STAT activation
      independent induction of ISGs, we used a mutant cell line in which both 337Y and
      512Y were substituted with phenylalanine (337F512F or FF mutant). In these cells,
      type I IFN failed to activate STAT1, STAT2, and STAT3 did not induce well
      characterized ISGs and did not exert antiviral or antiproliferative effects.
      Using Oligonucleotide array (Affymetrix) analysis, we showed that interferon
      regulatory factor-9 (IRF-9) was the only gene induced by IFN-beta in FF cells.
      Transient transfection analysis using an IRF-9 promoter-reporter luciferase
      construct in FF cells confirmed induction of the IRF-9 transcription unit by IFN
      beta. EMSA analysis using an IFN-stimulated response element (ISRE)-like sequence
      on the IRF-9 promoter detected 2 novel DNA-binding complexes induced in nuclear
      extracts of IFN-beta-treated FF cells. Supershift experiments identified the
      proteins IRF-1 and C/EBP-beta in the complex. These studies provide the first
      evidence that signaling pathways leading to gene transcription are activated by
      IFN-beta independent of STAT phosphorylation.

PMID- 20038198
TI  - FTY720 promotes local microvascular network formation and regeneration of cranial
      bone defects.
AB  - The calvarial bone microenvironment contains a unique progenitor niche that
      should be considered for therapeutic manipulation when designing regeneration
      strategies. Recently, our group demonstrated that cells isolated from the dura
      are multipotent and exhibit expansion potential and robust mineralization on
      biodegradable constructs in vitro. In this study, we evaluate the effectiveness
      of healing critical-sized cranial bone defects by enhancing microvascular network
      growth and host dura progenitor trafficking to the defect space pharmacologically
      by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We
      demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P(1)
      and S1P(3) significantly increase bone ingrowth, total microvessel density, and
      smooth muscle cell investment on nascent microvessels within the defect space.
      Further, in vitro proliferation and migration studies suggest that selective
      activation of S1P(3) promotes recruitment and growth of osteoblastic progenitors
      from the meningeal dura mater.

PMID- 20038199
TI  - The proteoglycan metabolism of articular cartilage in joint-scale culture.
AB  - Understanding and controlling chondrocyte and cartilage metabolism in
      osteochondral tissues may facilitate ex vivo maintenance and application, both
      for allografts and tissue-engineered grafts. The hypothesis of this study was
      that maintenance of chondrocyte viability and matrix content and release of
      sulfated glycosaminoglycan (sGAG) in the articular cartilage of joint-scale
      osteochondral fragments are temperature and metabolism dependent. The aims were
      to assess, for adult goat joints, the effects of incubation temperature (37
      degrees C vs. 4 degrees C) on cartilage chondrocyte viability and tissue matrix
      content and mechanical function, and the effects of temperature and cellular
      biosynthesis on sGAG release. Chondrocyte viability was maintained with 37
      degrees C incubation for 28 days, but decreased by approximately 30% with 4
      degrees C incubation. Concomitantly, with 37 degrees C incubation, cartilage sGAG
      was depleted by approximately 52% with the lost sGAG predominantly unable to
      aggregate with hyaluronan, whereas collagen content, tissue thickness, and tissue
      stiffness were maintained. The depletion of sGAG was diminished by slowing
      metabolism, with 4 degrees C decreasing release by approximately 79% compared
      with 37 degrees C incubation, and cycloheximide inhibition of cell metabolism at
      37 degrees C decreasing release by approximately 47%. These results indicate that
      the articular cartilage of joint-scale grafts have enhanced chondrocyte viability
      with incubation at 37 degrees C, but may need anabolic stimuli or catabolic
      inhibitors to maintain sGAG content.

PMID- 20038200
TI  - Identification of cellular genes induced in human cells after activation of the
      OAS/RNaseL pathway by vaccinia virus recombinants expressing these antiviral
      enzymes.
AB  - Interferon (IFN) type I induces the expression of antiviral proteins such as
      2',5'-oligoadenylate synthetases (OAS). The enzyme OAS is activated by dsRNA to
      produce 5'-phosphorylated, 2-5-linked oligoadenylates (2-5A) that activate RNaseL
      which, in turn, triggers RNA breakdown, leading to multiple biological functions.
      Although RNaseL is required for IFN antiviral function, there are many aspects of
      the molecular mechanisms that remain obscure. Here, we have used microarray
      analyses from human HeLa cells infected with vaccinia virus (VACV) recombinants
      expressing OAS-RNaseL enzymes (referred as 2-5A system) with the aim to identify
      host genes that are up- or down-regulated in the course of infection by the
      activation of this antiviral pathway. We found that activation of the 2-5A system
      from VACV recombinants produces a remarkable stimulation of transcription for
      genes that regulate many cellular processes, like those that promote cell growth
      arrest, GADD45B and KCTD11, apoptosis as CUL2, PDCD6, and TNFAIP8L2, IFN
      stimulated genes as IFI6, and related to tumor suppression as PLA2G2A. The 2-5A
      system activation produces down-regulation of transcription of some genes that
      promote cell growth as RUNX2 and ESR2 and of genes in charge to maintain
      mitochondria homeostasis as MIPEP and COX5A. These results reveal new genes
      induced in response to the activation of the 2-5A system with roles in apoptosis,
      translational control, cell growth arrest, and tumor suppression.

PMID- 20038201
TI  - A novel single-step self-assembly approach for the fabrication of tissue
      engineered vascular constructs.
AB  - There is a clinical need for a functional tissue-engineered blood vessel because
      small-caliber arterial graft (<5 mm) applications are limited by the availability
      of suitable autologous vessels and suboptimal performances of synthetic grafts.
      This study presents an analysis of the mechanical properties of tissue-engineered
      vascular constructs produced using a novel single-step self-assembly approach.
      Briefly, the tissue-engineered vascular media were produced by culturing smooth
      muscle cell in the presence of sodium l-ascorbate until the formation of a
      cohesive tissue sheet. This sheet was then rolled around a tubular support to
      create a media construct. Alternatively, the tissue-engineered vascular
      adventitia was produced by rolling a tissue sheet obtained from dermal
      fibroblasts or saphenous vein fibroblasts. The standard self-assembly approach to
      obtain the two-layer tissue-engineered vascular constructs comprising both media
      and adventitia constructs consists of two steps in which tissue-engineered
      vascular media were first rolled on a tubular support and a tissue-engineered
      vascular adventitia was then rolled on top of the first layer. This study reports
      an original alternative method for assembling tissue-engineered vascular
      constructs comprising both media and an adventitia in a single step by rolling a
      continuous tissue sheet containing both cell types contiguously. This tissue
      sheet was produced by growing smooth muscle cells alongside fibroblasts
      (saphenous vein fibroblasts or dermal fibroblasts) in the same culture dish
      separated by a spacer, which is removed later in the culture period. The
      mechanical strength assessed by uniaxial tensile testing, burst pressure
      measurements, and viscoelastic behavior evaluated by stepwise stress relaxation
      tests reveals that the new single-step fabrication method significantly improves
      the mechanical properties of tissue-engineered vascular construct for both
      ultimate tensile strength and all the viscoelastic moduli.

PMID- 20038202
TI  - Efficient plant-based production of chicken interleukin-12 yields a strong
      immunostimulatory cytokine.
AB  - Interleukin-12 (IL-12), an important immunomodulator for cell-mediated immunity,
      shows significant potential as a vaccine adjuvant and anticancer therapeutic in
      mammals. Therapeutic strategies to develop mammalian IL-12 as a vaccine
      adjuvant/immunomodulator for promoting cellular immunity and establishing a Th1
      biased immune response further support the potential value of ChIL-12. Transgenic
      plants show promise as scalable bioproduction platforms for challenging
      biopharmaceutical proteins. We have expressed, characterized, and purified
      biologically active ChIL-12 in plants using a rapid Agrobacterium-mediated
      tobacco plant-based transient expression system. To ensure the stoichiometric
      expression and assembly of p35 and p40, we expressed a single-chain version of
      chicken IL-12 (ChIL-12). A histidine 6x tag was used for identity and
      purification of ChIL-12(His) protein. Our results demonstrated precise cleavage
      of the endogenous chicken p40 signal peptide in plants as well as addition of N
      linked glycans. Biological activity was confirmed in vitro by interferon-gamma
      secretion of ChIL-12-treated chicken splenocytes. In addition, splenocytes
      treated with ChIL-12 expressed with or without the His tag demonstrated
      comparable ChIFN-gamma induction. These studies indicate that plant-based
      platforms for bioproduction of complex pharmaceutical proteins produce functional
      ChIL-12 and provide key advantages in safety, scale, and cost-effective platform
      for veterinary vaccine and therapeutic applications.

PMID- 20038203
TI  - Rare human IFNG variants.
AB  - After the identification of the human interferon-gamma (IFNG) variant G54D
      (c.287G>A, ss105106770) in DNA samples from Ghana, West Africa, systematic
      mutation screening of IFNG by the LightCycler((R))-based procedure of high
      resolution melting (HRM) revealed additional rare mutations. All variants
      occurred heterozygously only and were confirmed either by their detection in
      other individuals and/or by repeated DNA sequencing of independent PCR products.

PMID- 20038205
TI  - Endogenous collagen influences differentiation of human multipotent mesenchymal
      stromal cells.
AB  - Human multipotent mesenchymal stromal cells (hMSCs) are multipotent cells that,
      in the presence of appropriate stimuli, can differentiate into different lineages
      such as the osteogenic, chondrogenic, and adipogenic lineages. In the presence of
      ascorbic acid, MSCs secrete an extracellular matrix mainly composed of collagen
      type I. Here we assessed the potential role of endogenous collagen synthesis in
      hMSC differentiation and stem cell maintenance. We observed a sharp reduction in
      proliferation rate of hMSCs in the absence of ascorbic acid, concomitant with a
      reduction in osteogenesis in vitro and bone formation in vivo. In line with a
      positive role for collagen type I in osteogenesis, gene expression profiling of
      hMSCs cultured in the absence of ascorbic acid demonstrated increased expression
      of genes involved in adipogenesis and chondrogenesis and a reduction in
      expression of osteogenic genes. We also observed that matrix remodeling and anti
      osteoclastogenic signals were high in the presence of ascorbic acid. The presence
      of collagen type I during the expansion phase of hMSCs did not affect their
      osteogenic and adipogenic differentiation potential. In conclusion, the
      collagenous matrix supports both proliferation and differentiation of osteogenic
      hMSCs but, on the other hand, presents signals stimulating matrix remodeling and
      inhibiting osteoclastogenesis.

PMID- 20038204
TI  - Inhibition of type III interferon activity by orthopoxvirus immunomodulatory
      proteins.
AB  - The type III interferon (IFN) family elicits an antiviral response that is nearly
      identical to that evoked by IFN-alpha/beta. However, these cytokines (known as
      IFN-lambda1, 2, and 3) signal through a distinct receptor, and thus may be
      resistant to the evasion strategies used by some viruses to avoid the IFN
      alpha/beta response. Orthopoxviruses are highly resistant to IFN-alpha/beta
      because they encode well-characterized immunomodulatory proteins that inhibit IFN
      activity. These include a secreted receptor (B18R) that neutralizes IFN
      alpha/beta, and a cytoplasmic protein (E3L) that blocks IFN-alpha/beta effector
      functions in infected cells. We therefore determined the ability of these
      immunomodulators to abrogate the IFN-lambda-induced antiviral response. We found
      that (i) vaccinia virus (VACV) replication is resistant to IFN-lambda antiviral
      activity; (ii) neither VACV B18R nor the variola virus homolog B20R neutralizes
      IFN-lambda; (iii) VACV E3L inhibits the IFN-lambda-mediated antiviral response
      through a PKR-dependent pathway; (iv) VACV infection inhibits IFN-lambdaR
      mediated signal transduction and gene expression. These results demonstrate
      differential sensitivity of IFN-lambda to multiple distinct evasion mechanisms
      employed by a single virus.

PMID- 20038206
TI  - Interferon-alpha/beta genes are up-regulated in murine brain astrocytes after
      infection with Theiler's murine encephalomyelitis virus.
AB  - This article reports the production of interferon alpha/beta (IFN-alpha/beta) by
      SJL/J mouse brain astrocyte cultures infected with Theiler's murine
      encephalomyelitis virus (TMEV). cRNA from mock- and TMEV-infected SJL/J
      astrocytes was hybridized to the Affymetrix whole murine genome DNA microarray.
      Analysis revealed the up-regulation of 3 sequences coding for the IFN-alpha/beta
      domain. Increased expression of mRNA coding for IFN-alpha was shown by
      conventional RT-PCR and quantitative real-time RT-PCR. According to ELISA, the
      concentration of IFN-alpha in the supernatants of infected astrocyte cultures
      varied with the multiplicity of infection and post-infection time. The IFN
      alpha/beta secreted was biologically active, as shown by a virus-based IFN
      bioassay involving Cocal virus and TMEV infection. The contribution to total
      interferon activity was 29% +/- 3.0% for IFN-alpha and 52% +/- 3.6% for IFN-beta.
      IFN-alpha/beta was induced by whole TMEV virions; induction was not achieved with
      either purified isolated virion capsid proteins or UV-inactivated virus. Further,
      induction was inhibited by specific anti-TMEV antibodies. The receptor for IFN
      alpha/beta, which is absent in uninfected astrocytes, was up-regulated after
      infection, as suggested by DNA hybridization analysis. The brains of infected
      mice contained IFN-alpha/beta mRNA during the acute encephalitis phase, peaking
      at day 5 post-infection. Our findings could have significance for human diseases
      such as viral encephalitis and multiple sclerosis.

PMID- 20038208
TI  - Exposure to SO2 does not have a chronic effect on pulmonary functions of apricot
      workers.
AB  - The authors have previously demonstrated that apricot sulfurization workers
      develop asthma-like syndrome during apricot sulfurization due to exposure to
      sulfur dioxide (SO(2)) gas. The aim of the current study was to demonstrate if
      exposure to SO(2) gas had any chronic effects on pulmonary functions and
      bronchial reactivity of the workers. Twenty-five apricot sulfurization workers
      and a control group were included in the study. Physical examination, skin prick
      tests, pulmonary function tests (PFTs), and bronchoprovocation tests (BPTs) were
      performed before and after the season of sulfurization in the worker group. Skin
      prick tests, PFTs, and BPTs were performed also in the control group without a
      history of exposure to SO(2) gas. There was no statistically significant
      difference between PFT and BPT results of the workers and the control group.
      Comparison of the PFT results of the workers before and after the season of
      apricot sulfurization neither reveal a significant difference. Four (16%) out of
      25 workers were positive for BPTs before the period. Only one worker who had a
      negative BPT result before the sulfurization season was positive afterwards. The
      lack of a chronic effect on pulmonary functions is consistent with the diagnosis
      of asthma-like syndrome in apricot sulfurization workers.

PMID- 20038207
TI  - Double-stranded RNA-activated protein kinase regulates early innate immune
      responses during respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the most common cause of childhood viral
      bronchiolitis and lung injury. Inflammatory responses significantly contribute to
      lung pathologies during RSV infections and bronchiolitis but the exact mechanisms
      have not been completely defined. The double-stranded RNA-activated protein
      kinase (PKR) functions to inhibit viral replication and participates in several
      signaling pathways associated with innate inflammatory immune responses. Using a
      functionally defective PKR (PKR(-/-)) mouse model, we investigated the role of
      this kinase in early events of RSV-induced inflammation. Our data showed that
      bronchoalveolar lavage (BAL) fluid from infected PKR(-/-) mice had significantly
      lower levels of several innate inflammatory cytokines and chemokines.
      Histological examinations revealed that there was less lung injury in infected
      PKR(-/-) mice as compared to the wild type. A genome-wide analysis showed that
      several early antiviral and immune regulatory genes were affected by PKR
      activation. These data suggest that PKR is a signaling molecule for immune
      responses during RSV infections.

PMID- 20038209
TI  - Recombinant mouse granulocyte-macrophage colony-stimulating factor is
      glycosylated in transgenic tobacco and maintains its biological activity.
AB  - The granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with
      many important applications and, due to its immunostimulatory properties, could
      also be used as a vaccine adjuvant. A simple strategy to produce recombinant
      mouse GM-CSF (mGM-CSF) in transgenic Nicotiana tabacum plants was used in this
      study. The mGM-CSF cDNA followed by the sequence encoding endoplasmic reticulum
      retention signal (KDEL) was cloned into the ImpactVector under the control of the
      strong promoter from the gene encoding a small subunit of Rubisco. In transgenic
      plants the accumulation level of recombinant mGM-CSF varied in the individual
      transformants from 8 to 19 microg/g of fresh leaf tissue, which makes up to 0.22%
      of total soluble protein. In most analyzed plants, the apparent molecular weight
      of the recombinant protein was larger than predicted due to its N-glycosylation,
      presumably in 2 sites. The recombinant plant-produced murine GM-CSF retained its
      biological activity as confirmed in vitro in proliferation assay using a mouse
      cell line, which is growth-dependent on GM-CSF.

PMID- 20038210
TI  - Isoprinosine affects serum cytokine levels in healthy adults.
AB  - Isoprinosine is a synthetic purine derivative with immunomodulatory and antiviral
      properties, which result from an apparent in vivo enhancement of host immune
      responses. To evaluate the serum levels of certain cytokines during and after
      isoprinosine treatment, we assigned 10 healthy volunteers to receive isoprinosine
      1 g, 3 times daily, 5 consecutive days weekly. Both treatment and follow-up phase
      last 3 weeks. Interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-10, and
      tumor necrosis factor-alpha (TNF-alpha) were measured in serum using commercial
      ELISA kits at baseline, 7th, 10th, 14th, 21st, 28th, 35th, and 42nd day. We
      observed an increase in serum levels of all measured cytokines at 7th to 10th
      day. The levels of IL-2 had another raise at 42nd day after drop to initial
      values (P < 0.05; P < 0.001, respectively). Those of IL-10 held up enhanced from
      7th to 28th day of measurement (P < 0.01). There was a nearly flat line of values
      of TNF-alpha after initial slight increase at 10th day. We found a moderate
      negative correlation between IFN-gamma and IL-2, IL-10, and TNF-alpha (Spearman's
      r: -0.63, -0.62, -0.63; P < 0.05, respectively). We have demonstrated the
      immunomodulating properties of isoprinosine in healthy adults. It suggests
      resumption of the research with up-to-date methods to elucidate the mechanisms of
      action of inosine pranobex and maybe the other inosine compounds in different
      clinical settings.

PMID- 20038211
TI  - Human adipose-derived stromal cells accelerate diabetic wound healing: impact of
      cell formulation and delivery.
AB  - Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic
      potential in a variety of settings, including cutaneous wound healing; however,
      it is unknown whether the regenerative properties of this cell type can be
      applied to diabetic ulcers. ASCs collected from elective surgical procedures were
      used to treat full-thickness dermal wounds in leptin receptor-deficient (db/db)
      mice. Cells were delivered either as multicellular aggregates or as cell
      suspensions to determine the impact of cell formulation and delivery methods on
      biological activity and in vivo therapeutic effect. After treatment with ASCs
      that were formulated as multicellular aggregates, diabetic wounds experienced a
      significant increase in the rate of wound closure compared to wounds treated with
      an equal number of ASCs delivered in suspension. Analysis of culture supernatant
      and gene arrays indicated that ASCs formulated as three-dimensional aggregates
      produce significantly more extracellular matrix proteins (e.g., tenascin C,
      collagen VI alpha3, and fibronectin) and secreted soluble factors (e.g.,
      hepatocyte growth factor, matrix metalloproteinase-2, and matrix
      metalloproteinase-14) compared to monolayer culture. From these results, it is
      clear that cell culture, formulation, and delivery method have a large impact on
      the in vitro and in vivo biology of ASCs.

PMID- 20038213
TI  - Transdermal iontophoretic delivery of selegiline hydrochloride, in vitro.
AB  - Transdermal iontophoretic delivery of selegiline hydrochloride (SH) across
      dermatomed human skin was studied. Electrochemical stability and various factors
      affecting the skin permeation were investigated. SH was stable under the
      influence of an electrical field. The permeation of SH was very low by passive
      delivery (2.29 +/- 0.05 ug/cm2/h) as compared to iontophoresis at 0.5 mA/cm2
      (65.10 +/- 5.04 ug/cm2/h). An increase in drug concentration from 1 to 20 mg/mL
      increased the iontophoretic flux by 13-fold. Optimal pH and salt (NaCl)
      concentration for iontophoretic delivery of SH were found to be pH 5 and 100 mM,
      respectively. Overall, with 20 mg/mL SH and a current density of 0.4 mA/cm2, a
      maximum flux of 305.5 ug/cm2/h was obtained. Based on reported pharmacokinetic
      parameters, input target delivery rate to achieve effective plasma concentration
      of SH (2.2 ng/mL) was calculated. With a surface area of 40 cm2, iontophoretic
      delivery can provide six to seven times higher levels of SH than the target
      delivery rate, which enables lowering of the dose and/or patch surface area.
      Further in vivo studies will be required to prove the efficacy of ionophoresis
      for enhanced delivery of SH.

PMID- 20038212
TI  - Differential transcriptional responses to interferon-alpha and interferon-gamma
      in primary human hepatocytes.
AB  - Interferon (IFN) plays a central role in the innate and adaptive antiviral immune
      responses. While IFN-alpha is currently approved for treating chronic hepatitis B
      and hepatitis C, in limited studies, IFN-gamma has not been shown to be effective
      for chronic hepatitis B or C. To identify the potential mechanism underlying the
      differential antiviral effects of IFN-alpha and IFN-gamma, we used cDNA
      microarray to profile the global transcriptional response to IFN-alpha and IFN
      gamma in primary human hepatocytes, the target cell population of hepatitis
      viruses. Our results reveal distinct patterns of gene expression induced by these
      2 cytokines. Overall, IFN-alpha induces more genes than IFN-gamma at the
      transcriptional level. Distinct sets of genes were induced by IFN-alpha and IFN
      gamma with limited overlaps. IFN-alpha induces gene transcription at an early
      time point (6 h) but not at a later time point (18 h), while the effects of IFN
      gamma are more prominent at 18 h than at 6 h, suggesting a delayed
      transcriptional response to IFN-gamma in the hepatocytes. These findings indicate
      differential actions of IFN-alpha and IFN-gamma in the context of therapeutic
      intervention for chronic viral infections in the liver.

PMID- 20038214
TI  - Enhanced delivery of adenovirus, using proteoliposomes containing wildtype or
      V156K apolipoprotein A-I and dimyristoylphosphatidylcholine.
AB  - The delivery of genes or viruses via liposomes is a common approach used to
      enhance delivery efficiency. In the current study, to enhance delivery
      efficiency, proteoliposomes (PLs) containing adenovirus (Ad) were synthesized
      with dimyristoylphosphatidylcholine (DMPC), cholesterol, and apolipoprotein A-I
      (apoA-I). Wildtype apoA-I (WT) or V156K-apoA-I (V156K) was then used as an
      apolipoprotein to compare the structural and functional differences of the PLs.
      The particle diameter of V156K-PL-Ad was slightly larger than that of WT-PL-Ad,
      based on native gel electrophoresis. V156K showed more rapid phospholipid bilayer
      formation than did the WT, based on DMPC clearance. In addition, V156K exhibited
      maximal fluorescence that was more blue than that of WT in the PL state.
      Moreover, isothermal denaturation in response to the addition of guanidine
      hydrochloride (Gnd-HCl) revealed that V156K was more resistant, with no
      denaturation until 3 M Gnd-HCl was added. In addition, electron microscopy
      revealed that the viral particles were well associated with PL particles, which
      had a discoidal structure and were shaped like rouleaux. In addition, treatment
      of Ad in the PL state showed enhanced green fluorescent protein (GFP) expression
      when compared with treatment with Ad alone or with DMPC-Ad in hepatoma and brain
      glioma cells. Cells treated with WT-PL-Ad and V156K-PL-Ad showed approximately
      50% more GFP expression than cells treated with Ad alone or with DMPC-Ad after 24
      hr of incubation at 37 degrees C, indicating that viral stability was highly
      increased in the PL state. Furthermore, V156K-PL-Ad showed the highest expression
      of GFP in adult zebrafish (9 weeks old) at 5 days postinjection (10.5- and 3.8
      fold more GFP expressed than by Ad only and DMPC-Ad, respectively). In
      conclusion, the efficiency of viral delivery and the stability of the virus were
      significantly enhanced when PLs containing apoA-I were used in cellular and
      zebrafish models.

PMID- 20038215
TI  - Post-therapy calcification can result in false-positive fluorodeoxyglucose
      positron emission tomography scans in patients with non-Hodgkin's lymphoma.

PMID- 20038216
TI  - Granulocyte stimulating-colony factor-associated splenic artery rupture.

PMID- 20038217
TI  - Long-term safety and efficacy of cyclosporin A therapy for T-cell large granular
      lymphocyte leukemia.

PMID- 20038218
TI  - Experience with everolimus (RAD001), an oral mammalian target of rapamycin
      inhibitor, in patients with systemic mastocytosis.
AB  - KIT D816V mutation has been observed in more than 90% of patients with systemic
      mastocytosis (SM). This mutation constitutively activates the mammalian target of
      rapamycin (mTOR) signaling pathway. We tested the efficacy of everolimus
      (RAD001), a novel oral mTOR inhibitor, at a dose of 10 mg daily in an open label,
      non-comparative Phase II trial for patients with SM. Ten patients were enrolled
      from April 2007 to October 2008. Median age was 55 years, four were males, seven
      had indolent and three aggressive SM, and six were previously treated with other
      agents. Median duration of therapy was 4 months (range 0.2-18). No objective
      responses were noted. Four patients had a short-lasting subjective improvement in
      symptoms for a median duration of 3 months (range 3-15). Grade 1-3 diarrhea,
      mucositis, and neutropenia were the most common adverse effects. No Grade 4
      toxicity was noted. In conclusion, everolimus does not result in appreciable
      clinical activity in patients with SM.

PMID- 20038219
TI  - Mantle cell lymphoma: report of the 2009 Mantle Cell Lymphoma Consortium
      Workshop.
AB  - Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma characterized by
      cyclin D1 overexpression as a result of the t(11;14) chromosomal translocation,
      and by biological and clinical heterogeneity with frequent extranodal
      dissemination. There is no consensus or standard for initial therapy or for
      treatment of relapsed disease, and no proven curative therapy exists.
      Nonetheless, considerable progress in treatment response and survival has been
      realized over the past several years, and the disease remains an important focus
      of preclinical and clinical research. Advances in the biologic understanding of
      MCL, new molecular targets and therapeutic strategies, and the applications of
      biomarkers for risk stratification and molecular targeting were reviewed at a
      recent MCL Workshop. These are summarized herein, and are intended as both a
      status report on areas of active investigation and to serve as a template for
      future research.

PMID- 20038220
TI  - Metallothionein-I + II and receptor megalin are altered in relation to oxidative
      stress in cerebral lymphomas.
AB  - Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is
      highly malignant and has a poor prognosis. The PCNSL molecular features are
      reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL
      shows unique molecular profiles and a distinct clinical behavior. This article
      characterizes the histopathology and expression profiles of metallothionein-I +
      II (MT-I + II) and their receptor megalin along with proliferation, oxidative
      stress, and apoptosis in PCNSL and in central nervous system (CNS) lymphomas due
      to relapse from DLBCL (collectively referred to as CNS lymphoma). We show for the
      first time that MT-I + II and megalin are significantly altered in CNS lymphoma
      relative to controls (reactive lymph nodes and non-lymphoma brain tissue with
      neuropathology). MT-I + II are secreted in the CNS and are found mainly in the
      lymphomatous cells, while their receptor megalin is increased in cerebral cells.
      This morphology likely reflects the CNS lymphoma microenvironment and molecular
      interactions between lymphomatous and neuronal cells.

PMID- 20038221
TI  - High rate and prolonged duration of complete remissions induced by rituximab,
      methotrexate, doxorubicin, cyclophosphamide, vincristine, ifosfamide, etoposide,
      cytarabine, and thalidomide (R-MACLO-IVAM-T), a modification of the National
      Cancer Institute 89-C-41 regimen, in patients with newly diagnosed mantle cell
      lymphoma.
AB  - Novel therapeutic approaches are needed in mantle cell lymphoma (MCL). We
      conducted a phase II study in MCL testing an intensive regimen, R-MACLO-IVAM-T, a
      modification of the NCI 89-C-41 protocol. Newly diagnosed patients were treated
      with rituximab, methotrexate, doxorubicin, cyclophosphamide, and vincristine
      (cycle 1) followed by rituximab, ifosfamide (and mesna), etoposide, and
      cytarabine (cycle 2). These two cycles were repeated once, and patients achieving
      complete response (CR) received maintenance thalidomide. Among the 22 patients
      enrolled, 21 completed two or more cycles and achieved a CR. Three patients
      relapsed, while 17 are alive and relapse-free after a median follow-up of 37
      months (range 19-65 months). Two patients died: one from sepsis during cycle 1
      and another at 38 months while in remission from MCL. The progression-free
      survival at 3 years was 78% (95% CI: 51-91%). These results compare favorably
      with previously reported outcomes suggesting that durable remissions can be
      achieved without myeloablative therapy.

PMID- 20038222
TI  - Quantifying mutated and unmutated BCR-ABL transcripts confirms suitability of
      direct sequencing sensitivity in mutation analysis of patients with chronic
      myeloid leukemia with secondary resistance to tyrosine kinase inhibitors,
      regardless of ratio values.

PMID- 20038223
TI  - Treatment of aggressive systemic mastocytosis with daclizumab.

PMID- 20038224
TI  - Thalidomide-induced phrenic nerve paralysis.

PMID- 20038225
TI  - Treatment of t(11;18)-positive gastric mucosa-associated lymphoid tissue lymphoma
      with rituximab and chlorambucil: clinical, histological, and molecular follow-up.
AB  - Translocation t(11;18) is a factor predictive of poor response to treatment of
      gastric marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). We
      treated 13 patients with t(11;18)-positive gastric MALT lymphoma with the
      combination of rituximab and chlorambucil (nine patients as first treatment and
      four as second line therapy). The response to treatment was assessed on
      endoscopy, histology and molecular parameters including clonality and t(11;18)
      (median follow-up: 2 years). Macroscopic lesions disappeared in all cases.
      Histological remission was observed in 100% of the patients at the end of follow
      up. At week 25, B cell monoclonality and t(11;18)-positive tumor cells were still
      detected in 77% and 73%, respectively. However, at long term follow-up, the tumor
      B cell clone was present in only 30% whereas the t(11;18) was still detected in
      70%. The combination of rituximab - chlorambucil is highly effective in t(11;18)
      positive gastric MALT lymphoma. Molecular disease persists despite histological
      remission. t(11;18) is more sensitive than B cell clonality for the monitoring of
      residual molecular disease.

PMID- 20038226
TI  - Central nervous system involvement at presentation in childhood acute
      lymphoblastic leukemia: management experience and lessons.
AB  - This study was designed to analyze the spectrum of central nervous system (CNS)
      disease at diagnosis, traumatic lumbar puncture (TLP), role of cranial
      irradiation, prognostic parameters, and survival outcome in patients with CNS
      involvement amongst 747 patients with acute lymphoblastic leukemia managed at our
      center. Twenty-five and six patients had CNS disease and TLP, respectively.
      Patients with CNS involvement had significantly higher mean presenting leukocyte
      count (p = 0.021) and incidence of hyperleukocytosis (p = 0.01) compared to those
      without it. The outcome was poor with three patients in continuous complete
      remission, nine relapsers, eight deaths, and eight therapy defaulters. Three
      patients did not opt for therapy. CNS involvement was significantly associated
      with inferior survival by log-rank (p = 0.03) analysis but not by Cox
      multivariate (p = 0.145) analysis. CNS involvement is a high-risk indicator. Poor
      outcome in our cohort indicates the need for the revaluation of our treatment
      protocols with the inclusion of risk-stratified systemic therapy, categorization
      of CNS involvement into CNS1/CNS2/CNS3, and appropriate use of intrathecal
      therapy.

PMID- 20038227
TI  - Retreatment with rituximab in 178 patients with relapsed and refractory B-cell
      lymphomas: a single institution case control study.
AB  - The role of rituximab retreatment in relapsed B-cell lymphoma is not well known.
      We undertook a single center retrospective cohort study to investigate the
      efficacy of retreatment with rituximab with or without chemotherapy in patients
      with relapsed and refractory B-cell lymphomas. We only included patients treated
      first-line and in first progression; 178 patients were included in the study, of
      whom 29% had diffuse large B-cell lymphoma (DLBCL) and 28% had follicular
      lymphoma (FL). The overall response rate for the first treatment was 81% and for
      the second treatment was 66%. The median progression-free survival (PFS) for all
      patients from diagnosis was 13.2 months and from relapse was 12.5 months (not
      statistically different). For DLBCL the median PFS from diagnosis was 9.6 months
      and from relapse was 8.4 months, and for FL the median PFS from diagnosis was
      26.4 months and from relapse was 19.2 months (not statistically different). The 5
      year overall survival was 57%. In a historical comparison with rituximab-naive
      patients, rituximab-retreated patients had a shorter time to initial relapse than
      control patients, but there was no difference between the two groups for PFS from
      relapse. In conclusion, retreatment with rituximab, with or without chemotherapy,
      yields a high overall response rate in patients with relapsed and refractory B
      cell lymphomas. Relapse occurring after rituximab-containing therapy appears to
      be more aggressive than that occurring after chemotherapy alone. The outcome of
      retreatment, in terms of progression-free survival, is similar to that of primary
      treatment.

PMID- 20038228
TI  - Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue presenting
      with cryoglobulinemia and subtle marrow infiltrate.

PMID- 20038229
TI  - Chemokine polymorphisms and lymphoma: a pooled analysis.
AB  - Polymorphisms in chemokine genes have been associated with human immunodeficiency
      virus (HIV)-related non-Hodgkin lymphoma (NHL) but are understudied in non-HIV
      related NHL. Associations of NHL and NHL subtypes with polymorphisms and
      haplotypes in CCR5, CCR2, CCL5, CXCL12, and CX(3)CR(1) were explored in a pooled
      analysis of three case-control studies (San Francisco Bay Area, California;
      United Kingdom; total: cases N = 1610, controls N = 1992). Adjusted unconditional
      logistic regression was used to estimate relative risks among HIV-negative non
      Hispanic Caucasians. The CCR5 Delta32 deletion reduced the risk of NHL (odds
      ratio = 0.56, 95% confidence interval = 0.38-0.83) in men but not women with
      similar effects observed for diffuse large-cell and follicular lymphoma (FL). NHL
      risk also was reduced in men with the CCR2/CCR5 haplotype characterized by the
      CCR5 Delta32 deletion. The CCL5 -403A allele conferred reduced risks of FL and
      chronic lymphocytic leukemia/small lymphocytic lymphoma. Results should be
      interpreted conservatively. Continued investigation is warranted to confirm these
      findings.

PMID- 20038231
TI  - Use of dasatinib and nilotinib in imatinib-resistant chronic myeloid leukemia:
      translating preclinical findings to clinical practice.
AB  - The BCR-ABL inhibitor imatinib revolutionized the treatment of chronic myeloid
      leukemia (CML). However, resistance and intolerance to imatinib have emerged as
      substantial clinical issues. The mechanisms underlying resistance are
      multifactorial and may include mutations in the kinase domain of BCR-ABL,
      increased production of BCR-ABL, or activation of BCR-ABL-independent pathways.
      Two second-line BCR-ABL inhibitors are now approved for treatment of patients
      with resistance or intolerance to imatinib. Dasatinib is a dual BCR-ABL/Src
      family kinase (SFK) inhibitor approved for patients with imatinib-resistant and 
      intolerant CML in any phase and Ph+ ALL. Nilotinib, an analogue of imatinib, is
      approved for the treatment of imatinib-resistant or -intolerant patients with
      chronic or accelerated phase CML. Both agents have shown significant clinical
      activity in patients with imatinib-resistant or -intolerant CML, and their
      approval represents a major advancement in the treatment options available.
      Choosing the most appropriate treatment after imatinib failure may be critical in
      attaining the best possible long-term prognosis. The presence of certain disease
      characteristics (e.g. specific BCR-ABL mutations) or patient comorbidities may
      facilitate more effective treatment. In this review, we discuss mechanisms of
      imatinib resistance and preclinical and clinical data with dasatinib and
      nilotinib which may have potential use for guiding second-line treatment
      decisions.

PMID- 20038230
TI  - Effects of induction with novel agents versus conventional chemotherapy on
      mobilization and autologous stem cell transplant outcomes in multiple myeloma.
AB  - Multiple myeloma (MM) is the top indication for high-dose chemotherapy (HDC) with
      autologous stem cell transplantation (SCT), a strategy which improves progression
      free survival and potentially overall survival (OS). Novel induction regimens
      incorporating the immunomodulatory (IMID) agents, such as thalidomide and
      lenalidomide and the proteosome inhibitor bortezomib improve response rates and
      survival for newly diagnosed patients. Recent data temper enthusiasm for these
      treatments by illustrating difficulty in some circumstances with mobilizing
      CD34(+) hematopoietic stem cells for subsequent HDC/SCT. We compare conventional
      induction regimens with novel agent-based induction strategies and the associated
      effects on stem cell mobilization and HDC/SCT outcome in 224 patients. Although
      patients exposed to novel agent inductions collected generally fewer CD34(+)
      cells than patients induced with chemotherapy, these differences did not
      translate into adverse consequences with subsequent HDC/SCT. We show that an
      improvement in OS after HDC/SCT may be related to induction therapy with novel
      agents as opposed to chemotherapy. Our data extrapolate on prior work and expand
      on ongoing controversies about optimal induction regimens for patients with MM
      planned for subsequent HDC/SCT and optimal sequencing of therapies.

PMID- 20038232
TI  - Growth-inhibiting effects of arsenic trioxide plus epigenetic therapeutic agents
      on leukemia cell lines.
AB  - Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic
      leukemia (APL) and other hematopoietic malignancies. We found that ATO down
      regulated the global DNA methylation level in HL-60 cells with high-performance
      capillary electrophoresis (HPCE) assay. Using combination index method of Chou
      and Talalay, interactions between ATO and epigenetic therapeutic agents were
      analyzed in three human leukemia cell lines (HL-60, U937, and K562). A
      synergistic interaction was observed in HL-60 cells between ATO and 5-Aza-2'
      Deoxycytidine (DAC), while an antagonistic interaction was found in U937 cells
      between ATO and valproic acid (VPA). The combination of ATO with trichostatin A
      (TSA) caused an antagonistic interaction in U937 and K562 cells. These results
      not only highlight possible diversity of the anti-leukemia mechanisms of ATO, but
      also provide initial guide for further investigation of leukemia therapies based
      on the combination of ATO with epigenetic agents.

PMID- 20038233
TI  - Managing tumor lysis syndrome in 2010.

PMID- 20038234
TI  - Kinase domain mutations of BCR-ABL identified at diagnosis before imatinib-based
      therapy are associated with progression in patients with high Sokal risk chronic
      phase chronic myeloid leukemia.
AB  - Acquired resistance to imatinib in the advanced phase of chronic myeloid leukemia
      (CML) has been associated with mutations in the kinase domain (KD) of BCR-ABL. On
      the contrary, the prognostic implication of KD mutations in early chronic phase
      (CP) patients at diagnosis before imatinib-based therapy has not yet been
      established. We have reviewed the status of mutations in 43 patients with early
      CP-CML on the samples collected at diagnosis. Mutations were identified by direct
      sequencing (DS) with BidDye Terminator v 1.1. cycle sequencing kit and analyzed
      with a 3130 ABI capillary electrophoresis system. Eight out 13 (61.5%) high Sokal
      risk patients showed the following mutations: Y253C, S265R, E255K, F359Y, N374S,
      E255V, E255V, E255V. Three patients progressed during imatinib and second-line
      inhibitors and died of blastic phase CML at 23, 33, and 69 months. Another
      patient with intermediate Sokal risk showed D363G mutation at diagnosis,
      progressed under imatinib, was allografted and he is now alive in major molecular
      remission (MMR). No low-risk patient carried KD mutation at diagnosis. In
      conclusion, KD mutations conferring high-level imatinib resistance are present in
      patients with de novo CML and in some of them lead to disease progression.

PMID- 20038235
TI  - A phase I study of dacetuzumab (SGN-40, a humanized anti-CD40 monoclonal
      antibody) in patients with chronic lymphocytic leukemia.
AB  - Despite advances in therapy, chronic lymphocytic leukemia remains an incurable
      disease and novel, effective therapies are needed. In this open-label, dose
      escalation, phase I study, dacetuzumab (IgG1 humanized monoclonal antibody) was
      administered to 12 adults, all of whom had received several prior systemic
      therapies (median, 4; range, 2-11). Intrapatient dose escalation (maximum weekly
      doses of 3-8 mg/kg) was used to diminish first-dose-related inflammatory
      symptoms. No dose-limiting toxicities or dose-dependent trends in adverse events
      (AEs) were observed. The most common AEs (in >/=2 patients) were fatigue,
      headache, anorexia, conjunctivitis, hyperhidrosis, and night sweats, all of which
      were mild or moderate. No deaths, serious AEs, or discontinuations due to AEs
      occurred. Although no patient achieved an objective response, five patients
      demonstrated stable disease after 1 cycle of therapy, with no discernable
      correlation between dacetuzumab dose and outcome. This modest single-agent
      activity may warrant further testing of dacetuzumab in combination with other
      chronic lymphocytic leukemia therapies.

PMID- 20038236
TI  - SUVmax in FDG-PET at the biopsy site correlates with the proliferation potential
      of tumor cells in non-Hodgkin lymphoma.
AB  - The maximum standard uptake value (SUVmax) of the whole body on 18F
      fluorodeoxyglucose positron emission tomography (FDG-PET) reflects the tumor
      aggressiveness in non-Hodgkin lymphoma (NHL). To clarify the correlation between
      SUVmax at the biopsy site and the proliferation potential of tumor cells, we
      studied 36 patients with untreated NHL and five with untreated Hodgkin lymphoma
      (HL) by measuring the Ki-67 proliferation index (MIB-1 labeling index) in biopsy
      specimens. The measured MIB-1 labeling index was categorized into seven levels:
      nearly 0%, 5-20%, 21-40%, 41-60%, 61-80%, 81-95%, and nearly 100%. Twenty-four
      lymph nodes (LNs) and 17 extranodal (EN) sites were biopsied. The reviewed
      diagnosis was eight indolent lymphomas, two mantle-cell lymphomas, 26 aggressive
      lymphomas, and five HLs. A positive correlation was observed between the SUVmax
      at the biopsy site and the MIB-1 labeling index in the 36 patients with NHL (r =
      0.69, p < 0.001). The correlations were also observed in LN group (r = 0.60, p =
      0.006) and EN group (r = 0.87, p < 0.001), respectively. In the five patients
      with HL, the MIB-1 labeling index was uniformly categorized in nearly 100%. The
      SUVmax correlates with the proliferation potential in the case of NHL.

PMID- 20038237
TI  - Long term outcome of patients with localized aggressive non-Hodgkin lymphoma
      treated with PROMECE-CYTABOM plus involved-field radiation therapy: a study by
      the Gruppo Italiano Studio Linfomi.
AB  - We conducted a retrospective analysis on 168 adult patients with newly diagnosed,
      limited-stage (I and II) diffuse large B-cell lymphoma (DLBCL) treated from 1988
      to 2004 with PROMECE-CYTABOM (P-C) plus involved-field radiation therapy (IF-RT).
      At the end of P-C, the overall response rate was 92%. Radiotherapy (RT) was
      delivered to 84% of cases. With a median follow-up of 95 months, overall survival
      (OS), relapse free survival (RFS), and failure free survival at 5 and 10 years
      was 84% and 77%, 81% and 75%, 71% and 67%, respectively. Age (>60 years, p =
      0.002), serum albumin (<3.5 g/dL; p = 0.015), and RT (p < 0.001) were independent
      predictors of OS. For patients in complete remission the administration of RT
      didn't improve both RFS and OS. This study confirms that patients with localized
      aggressive lymphoma have a high chance of cure with anthracycline containing
      regimens. Though the regimen used to treat these patients does not contain
      rituximab, results are considered excellent both in terms of efficacy and safety.

PMID- 20038238
TI  - Rituximab-induced fatal interstitial pneumonitis: case report.

PMID- 20038239
TI  - Using positron emission tomography to assess tumor proliferation in non-Hodgkin
      lymphoma.

PMID- 20038240
TI  - Cerebrospinal fluid inflammatory cytokines and biomarkers of injury severity in
      acute human spinal cord injury.
AB  - There is an urgent need for both the scientific development and clinical
      validation of novel therapies for acute spinal cord injury (SCI). The scientific
      development of novel therapies would be facilitated by a better understanding of
      the acute pathophysiology of human SCI. Clinical validation of such therapies
      would be facilitated by the availability of biomarkers with which to stratify
      injury severity and predict neurological recovery. Cerebrospinal fluid (CSF)
      samples were obtained over a period of 72 h in 27 patients with complete SCI
      (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and
      serum samples using a multiplex cytokine array system and standard enzyme-linked
      immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and
      patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau,
      S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity
      dependent fashion. A biochemical model was established using S100beta, GFAP, and
      IL-8 to predict injury severity (ASIA A, B, or C). Using these protein
      concentrations at 24-h post injury, the model accurately predicted the observed
      ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months
      post injury was better predicted by these CSF proteins than with the patients'
      baseline ASIA grade. The pattern of expression over the first 3 to 4 days post
      injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1
      provides invaluable information about the pathophysiology of human SCI. A
      prediction model that could use such biological data to stratify injury severity
      and predict neurological outcome may be extremely useful for facilitating the
      clinical validation of novel treatments in acute human SCI.

PMID- 20038241
TI  - Association of human T lymphotropic virus 1 amplification of periodontitis
      severity with altered cytokine expression in response to a standard
      periodontopathogen infection.
AB  - BACKGROUND: Periodontal diseases (PDs) are infectious diseases in which
      periodontopathogens trigger chronic inflammatory and immune responses that lead
      to tissue destruction. Recently, viruses have been implicated in the pathogenesis
      of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present
      with abnormal oral health and a marked increased prevalence of periodontal
      disease. METHODS: In this study, we investigated the patterns of
      periodontopathogen infection and local inflammatory immune markers in HTLV-1
      seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared
      with HTLV-1-seronegative individuals with chronic periodontitis (CP group) and
      periodontally healthy, HTLV-1-seronegative individuals (control group). RESULTS:
      Patients in the CP/HTLV-1 group had significantly higher values of bleeding on
      probing, mean probing depth, and attachment loss than patients in the CP group.
      The expression of tumor necrosis factor alpha and interleukin (IL) 4 was found to
      be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended
      toward a higher expression in the CP/HTLV-1 group. A significant increase was
      seen in the levels of IL-1beta and interferon gamma in the CP/HTLV-1 group
      compared with the CP group, whereas expression of the regulatory T cell marker
      FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1
      group. Interestingly, similar frequency and/or load of periodontopathogens
      (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and
      Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex
      virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically
      associated with PDs were found in the CP/HTLV and CP groups. CONCLUSIONS: HTLV-1
      may play a critical role in the pathogenesis of periodontal disease through the
      deregulation of the local cytokine network, resulting in an exacerbated response
      against a standard periodontopathogen infection.

PMID- 20038243
TI  - Cryptococcosis in the developing world: an elephant in the parlor.

PMID- 20038242
TI  - Escherichia coli Pyomyositis: an emerging infectious disease among patients with
      hematologic malignancies.
AB  - BACKGROUND: Pyomyositis is typically caused by gram-positive bacteria, especially
      Staphylococcus aureus. Few cases of Escherichia coli pyomyositis have been
      reported, including only 1 involving a patient with a hematologic malignancy.
      METHODS: The clinical microbiology database at The M. D. Anderson Cancer Center
      (Houston, TX) was reviewed for the period January 2003 through December 2007 to
      identify cases of E. coli pyomyositis. Clinical characteristics, laboratory and
      radiologic findings, treatment, and outcomes were recorded. Available isolates
      underwent phylogenetic group determination, virulence genotyping, multilocus
      sequence typing, repetitive-element polymerase chain reaction, and pulsed-field
      gel electrophoresis. RESULTS: Six cases of E. coli pyomyositis were identified.
      All patients were receiving chemotherapy for a hematologic malignancy; 5 were
      severely neutropenic. Three patients became hypotensive, 2 required intensive
      care, and 2 (33%) died, despite receiving carbapenem therapy. All E. coli
      isolates were fluoroquinolone resistant; 55% produced an extended-spectrum beta
      lactamase (ESBL). Five of 6 available isolates belonged to phylogenetic group B2,
      had similar virulence factor profiles, exhibited > 95% similar repetitive-element
      polymerase chain reaction profiles, and represented sequence type ST131; however,
      all had unique pulsed-field gel electrophoresis profiles. CONCLUSIONS: E. coli
      pyomyositis has emerged as a serious problem among our patients with hematologic
      malignancy. It usually is caused by members of E. coli ST131, a recently
      identified cause of fluoroquinolone-resistant, ESBL-positive E. coli infection
      worldwide. Awareness of this emerging syndrome and the usual causative agent is
      important to ensure appropriate management when febrile, neutropenic patients
      with hematologic malignancy exhibit signs of localized muscle infection.

PMID- 20038245
TI  - Using multimedia technology to help combat the negative effects of protective
      isolation on patients: the Open Window project--an engineering challenge.
AB  - The Open Window project was established with the aim of creating a "virtual
      window" for each patient who is confined to protective isolation due to treatment
      for illness. This virtual window as developed provides a range of media or
      experiences. This paper describes the approach taken to the system design and
      discusses initial experiences with implementing such a system in a critical care
      setting. The system design was predicated on two guiding principles. Firstly it
      should be intuitive to use and the technology used to create the virtual window
      hidden from patient view. Secondly the system must be able to be installed at the
      point of care in a way that delivers the experience under the patient's control,
      without compromising the function or safety of the clinical environment. Patient
      acceptance of the system is being measured as part of an on-going trial and at
      this interim phase of data analysis 100% (n=55) of participants in the
      intervention group have reported that the technology was easy to use. We conclude
      that the system as designed and installed is an effective, robust and reliable
      system upon which to base a multimedia interventions in a critical care room.

PMID- 20038246
TI  - Audrey Juliet Arnott (1901-1974): the legacy of an artist in neurosurgery.
AB  - Audrey Arnott, a graduate of the Royal College of Art, was first employed as an
      artist by Hugh Cairns at the London Hospital. Cairns arranged for Arnott to be
      trained as a medical illustrator under Max Brodel, a close friend of Harvey
      Cushing and founder of the first 'Department of Art as Applied to Medicine' at
      Johns Hopkins University. During her time at John Hopkins Arnott developed a
      close friendship with Dorcas Padget, medical illustrator to Walter Dandy. Arnott
      was a highly accomplished artist and trained numerous other British medical
      illustrators and was one of the founders of the Medical Artists Association.
      Arnott's training and friendship with Brodel and Padget enabled her to pass on a
      legacy of neurosurgical illustration to the United Kingdom.

PMID- 20038244
TI  - Combination flucytosine and high-dose fluconazole compared with fluconazole
      monotherapy for the treatment of cryptococcal meningitis: a randomized trial in
      Malawi.
AB  - BACKGROUND: Cryptococcal meningitis is a major cause of human immunodeficiency
      virus (HIV)-associated morbidity and mortality in Africa. Improved oral treatment
      regimens are needed because amphotericin B is neither available nor feasible in
      many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than
      at a dosage of 800 mg per day, but mortality rates remain unacceptably high.
      Therefore, we examined the effect of adding oral flucytosine to fluconazole.
      METHODS: From 13 February through 2 December 2008, HIV-seropositive,
      antiretroviral-naive patients experiencing their first episode of cryptococcal
      meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per
      day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by
      fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up.
      The primary end point was early fungicidal activity, derived from quantitative
      cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were
      safety and 2- and 10-week mortality. RESULTS: Forty-one patients were analyzed.
      Baseline mental status, cryptococcal burden, opening pressure, CD4(+) cell count,
      and HIV load were similar between groups. Combination therapy was more fungicidal
      than fluconazole alone (mean early fungicidal activity +/- standard deviation 
      0.28 +/- 0.17 log colony-forming units [CFU]/mL per day vs -0.11 +/- 0.09 log
      CFU/mL per day; P < .001). The combination arm had fewer deaths by 2 weeks (10%
      vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia
      with combination therapy (5 vs 1, within the first 2 weeks; P = .20), but there
      was no increase in infection-related adverse events. CONCLUSIONS: The results
      suggest that optimal oral treatment for cryptococcal meningitis is high-dose
      fluconazole with flucytosine. Efforts are needed to increase availability of
      flucytosine in Africa. Clinical trials registration. isrctn.org Identifier:
      ISRCTN02725351.

PMID- 20038247
TI  - Barriers to hepatitis B vaccine coverage among healthcare workers in the Republic
      of Georgia: An international perspective.
AB  - BACKGROUND: While the Republic of Georgia has a high prevalence of hepatitis B
      virus (HBV) infection (3.4% of blood donors tested positive for HBV surface
      antigen [HBsAg]), relatively few healthcare workers (HCWs) are thought to be
      immunized. OBJECTIVE: To measure rates of HBV vaccination coverage and identify
      predictors of vaccine acceptance among HCWs. DESIGN: Cross-sectional survey.
      METHODS: A study was conducted among full-time physicians and nurses at 2 large
      hospitals. Self-administered questionnaires included questions about demographic
      characteristics, HBV vaccine status, willingness to recommend vaccination to
      other HCWs, and barriers to vaccination. Laboratory tests were conducted for
      identification of HBsAg and antibody to hepatitis B core antigen. RESULTS: A
      total of 297 (91%) of 325 randomly selected HCWs provided information for the
      study (124 physicians and 173 nurses). The rate of HBV vaccination coverage was
      12%, and 54% of respondents indicated that they would recommend vaccination to
      other HCWs. Perception of vaccine safety was identified as the most important
      predictor for acceptance (prevalence ratio [PR], 3.3 [95% confidence ratio {CI},
      1.2-8.9]) and for willingness to recommend HBV vaccination to other HCWs (PR, 5.5
      [95% CI, 3.1-9.4]). Vaccinated HCWs were more likely to recommend vaccination to
      other healthcare personnel (PR, 1.7 [95% CI, 1.5-2.1]), as were those younger
      than 40 years of age (PR, 6.0 [95% CI, 2.8-12.6]). Multivariate analyses
      identified 2 additional factors associated with vaccine acceptance and
      willingness to recommend vaccination: the hospital at which the HCW was employed
      and the perception of risk of infection for HCWs. CONCLUSION: Georgia plans a
      major HBV vaccination campaign for HCWs in 2009. The campaign's success will
      depend on addressing vaccine safety concerns identified in this study and
      educating HCWs about risk factors for infection and benefits of immunization.

PMID- 20038248
TI  - Policy implications of the society for healthcare epidemiology of America's
      research plan for reducing healthcare-associated infections.

PMID- 20038250
TI  - The biological effect of an antisense oligonucleotide depends on its route of
      endocytosis and trafficking.
AB  - We demonstrate that the biological effect of an oligonucleotide is influenced by
      its route of cellular uptake. Utilizing a splice-switching antisense
      oligonucleotide (SSO) and a sensitive reporter assay involving correction of RNA
      splicing, we examined induction of luciferase in cells treated either with
      various concentrations of an unconjugated ("free") SSO or an SSO conjugated to a
      bivalent RGD ligand that promotes binding to the alphavbeta3 integrin (RGD-SSO).
      Under conditions of equal accumulation in cells, the RGD-SSO consistently had a
      greater effect on luciferase induction than the unconjugated SSO. We determined
      that the RGD-SSO and the unconjugated SSO were internalized by distinct
      endocytotic pathways, suggesting that the route of internalization affects the
      magnitude of the biological response.

PMID- 20038249
TI  - Enhancing patient safety by reducing healthcare-associated infections: the role
      of discovery and dissemination.
AB  - Healthcare-associated infections (HAIs) take a major human toll on society and
      reduce public confidence in the healthcare system. The current convergence of
      scientific, public, and legislative interest in reducing rates of HAI can provide
      the necessary momentum to address and answer important questions in HAI research.
      This position paper outlines priorities for a national approach to HAIs:
      scrutinizing the science base, developing a prioritized research agenda,
      conducting studies that address the questions that have been identified, creating
      and deploying guidelines that are based on the outcomes of these studies, and
      then initiating new studies that assess the efficacy of the interventions.

PMID- 20038251
TI  - Light-induced gene expression using messenger RNA molecules.
AB  - The exploration of messenger RNA (mRNA) as a potential therapeutic regulator of
      gene expression has been significantly reduced by the inability of polyplexes to
      escape the endocytic pathway, combined with the lack of specific targeting. In
      the present study, we have developed a site-specific delivery strategy for mRNA
      molecules through the use of photochemical internalization (PCI) technology. When
      using EGFP mRNA as a model system, a 10- to 40-fold increase in EGFP-positive
      cells was obtainable in PCI-treated samples, compared to untreated PCI samples in
      a human osteosarcoma cell line. The amount of EGFP-positive cells in both PCI and
      non PCI-treated samples were highly dependent on the nitrogen/phosphate (N/P)
      ratio. Potent delivery of mRNA molecules through the endocytic pathway by the use
      of polyplexes and PCI was achievable without any loss of cell viability. The main
      benefit of the strategy proposed is the possibility for protein production from
      the delivered mRNA in a way that is controllable in a time- and site-specific
      manner.

PMID- 20038252
TI  - Specific regulation of point-mutated K-ras-immortalized cell proliferation by a
      photodynamic antisense strategy.
AB  - It has been reported that point mutations in genes are responsible for various
      cancers, and the selective regulation of gene expression is an important factor
      in developing new types of anticancer drugs. To develop effective drugs for the
      regulation of point-mutated genes, we focused on photoreactive antisense
      oligonucleotides. Previously, we reported that photoreactive oligonucleotides
      containing 2'-O-psoralenylmethoxyethyl adenosine (2'-Ps-eom) showed drastic
      photoreactivity in a strictly sequence-specific manner. Here, we demonstrated the
      specific gene regulatory effects of 2'-Ps-eom on [(12)Val]K-ras mutant (GGT -->
      GTT). Photo-cross-linking between target mRNAs and 2'-Ps-eom was sequence
      specific, and the effect was UVA irradiation-dependent. Furthermore, 2'-Ps-eom
      was able to inhibit K-ras-immortalized cell proliferation (K12V) but not Vco
      cells that have the wild-type K-ras gene. These results suggest that the 2'-Ps
      eom will be a powerful nucleic acid drug to inhibit the expression of disease
      causing point mutation genes, and has great therapeutic potential in the
      treatment of cancer.

PMID- 20038253
TI  - Off-target analysis of control siRNA molecules reveals important differences in
      the cytokine profile and inflammation response of human fibroblasts.
AB  - The use of RNA interference for the manipulation of gene expression has seen
      great applications from basic science to clinical investigations. However,
      limited selectivity and the induction of off-target effects by double stranded
      RNA molecules have been analyzed and discussed since the discovery of this gene
      expression regulation mechanism. In this study, the specificity of 13
      commercially available control siRNA molecules is addressed by the analysis of
      gene expression profiles in 2 human cell lines HT1080 and HaCaT and in the mouse
      cell line 3T3-L1. The off-target signatures of the transfected siRNA molecules
      differ greatly between the cell lines and only a small overlap was seen for the 2
      human cell lines. In particular, the HT1080 cell line showed the highest number
      of detected gene expression differences. In these cells, several different
      control siRNA molecules activated a common profile of 79 deregulated genes
      including a reduced interleukin-1beta (IL-1beta) and IL-24 expression. Functional
      analysis of MMP1 secretion and tumor necrosis factor-alpha (TNF-alpha) induced IL
      8 release revealed a reduction of NFkappaB signaling caused by at least 2 out of
      the 13 tested control siRNA molecules. Our findings strongly argue for a careful
      analysis of the control siRNA molecules for any given RNAi experiment.

PMID- 20038254
TI  - Improving long-term weight management: social capital and missed opportunities.

PMID- 20038255
TI  - Worksite health promotion: the value of the Tune Up Your Heart program.
AB  - Successful wellness initiatives at DaimlerChrysler Canada Incorporated (DCCI) led
      to a unique partnership between key stakeholders that allowed implementation of
      Tune Up Your Heart, a program aimed at improving workforce cardiovascular disease
      (CVD) risk. Volunteers were screened and stratified according to their CVD risk.
      Interventions were tailored to risk level and included goal setting, monitoring
      progress, and company-wide education programs. Outcome data (CVD risk and
      components of risk) were collected at study entry and after 18 months. The
      economic impact of the program was determined using a model based on subject
      movement across risk categories and historical claims data for life insurance,
      short- and long-term disability, prescription drugs, and casual absenteeism.
      Intervention participants (N = 343) demonstrated a significant (P = .0113)
      relative CVD risk reduction of 12.7%; 36% of participants lost weight, and
      average body mass index decreased from 28.4 to 28.2 (P = .0419). Average systolic
      and diastolic blood pressure significantly decreased (P < .0001 and P = .0221,
      respectively). Subjects reported increased adherence to recommended exercise and
      diet regimens, and the number of smokers decreased by 14%. The majority of
      subjects reported satisfaction with the program. Annual savings were estimated at
      Can$793 for the intervention group and Can$18,461 when projected to the entire
      workforce (N = 13,629). Savings were sensitive to cost weighting when subjects
      moved to a lower risk class but more robust to other parameters. The Tune Up Your
      Heart program significantly improved employee CVD risk profile, and was
      associated with savings for DCCI.

PMID- 20038256
TI  - Obesity management interventions: a review of the evidence.
AB  - The burden of disease associated with the obesity epidemic shortens lives, and
      prevalence is accelerating. As with other chronic diseases, improved outcomes are
      associated with effective self-management of obesity across the life span. The
      disease of obesity, then, fits squarely within the disease management and chronic
      care models. This article reviews selected interventions, described in peer
      reviewed literature, designed to achieve significant weight loss for individuals
      identified as overweight or obese. The study objective is to provide an overview
      of the full range of methods and models for weight loss, including some available
      without medical supervision. The intended audience includes individuals and
      organizations with an expressed interest in disease management and the chronic
      care models. Our review identified promising lines of investigation for future
      research that span diverse medical disciplines applied to obesity. The quality of
      the studies included in our review was uneven, and compromises the current
      evidence for effectiveness and efficacy. Generally, our results showed that
      combination approaches-surgical or pharmacologic, combined with a behavioral
      intervention-were most likely to be effective.

PMID- 20038257
TI  - Review of insomnia pharmacotherapy options for the elderly: implications for
      managed care.
AB  - The prevalence of insomnia in the elderly is significant. If left untreated or
      inappropriately treated, insomnia may contribute to increased health care
      resource use. Therefore, better identification and management of insomnia is
      required for this patient population. The etiology and magnitude of insomnia due
      to changes in circadian rhythms, comorbid conditions, and pharmaceutical agents
      are not well documented, and the utilization of over-the-counter and non-Food and
      Drug Administration (FDA)-approved agents to induce sleep (including
      antihistamines and ethyl alcohol) have not been studied in a natural setting.
      Evaluating the actual type of insomnia remains much more art than science for the
      majority of patients and providers. Another issue to consider in this population
      involves the relationship between patient and physician and the traditional
      passive patient role. Nonpharmacologic approaches (ie, cognitive behavioral
      therapy) for insomnia management are effective and usually are first-line
      therapy. However, the challenges to implementing these approaches may limit their
      use, thus necessitating pharmacologic therapy. There are currently 3 FDA-approved
      drug classes for the treatment of insomnia: benzodiazepines, benzodiazepine
      receptor agonists, and melatonin receptor agonists. Although all agents in these
      classes are efficacious, benzodiazepines and benzodiazepine receptor agonists are
      associated with adverse events that must be considered when treating insomnia in
      the elderly. Melatonin agonists have a mechanism of action that regulates normal
      sleep-wake cycles and readjusts circadian rhythms, which may confer a better
      safety profile than traditional sedative-hypnotics that target gamma-aminobutyric
      acid receptors. Because the 3 currently approved drug classes for insomnia have
      similar efficacy, safety considerations should be of paramount importance for the
      elderly patient; however, additional data are needed to appropriately assess the
      risk-benefit ratios of each.

PMID- 20038258
TI  - Improving the imputation of race: evaluating the benefits of stratifying by age.
AB  - Health plans and other health care institutions may use indirect methods such as
      geocoding and surname analysis to estimate race, ethnicity, and socioeconomic
      status in an effort to measure disparities in care or target specific
      demographics. This study investigated whether stratifying by age improved
      imputations of race and ethnicity made through geocoding. Self-reported race and
      ethnicity from Medicaid enrollment records and from a health risk assessment
      administered by a large employer were used to validate imputation results from
      both an age-stratified model and a standard model. Sensitivity, specificity, and
      positive predictive value were calculated. Both approaches successfully imputed
      race and ethnicity for whites, blacks, Asians, and Hispanics. The age-stratified
      approach identified more blacks than did the unstratified approach, and correctly
      identified more blacks and whites. The two approaches worked equally well for
      identifying Asians and Hispanics. Age stratification may improve the accuracy of
      imputation methods, and help health care organizations to better understand the
      demographics of the people they serve.

PMID- 20038259
TI  - Impact of retail medicine on standard costs in primary care: a semiparametric
      analysis.
AB  - Retail medicine clinics have become widely available. However, few studies have
      been published that compare retail clinic costs of care to standard medical
      visits for similar patients. The purpose of this study was to compare standard
      medical costs during a 6-month period after visiting a retail medical clinic to
      care received in a conventional medical office setting. Medical records of
      primary care patients (both adults and children) seen in a large group practice
      in Minnesota in 2008 were analyzed for this study. Two groups of patients were
      studied: those who used a retail walk-in clinic (N = 141) and a comparison group
      who used regular office care for same-day, acute visits (N = 137). Patients
      treated for 5 common conditions (pink eye, sore throat, viral illness,
      bronchitis, and cough) were selected. The dependent variables were standard costs
      using federal rates and the rank of standard costs. Multiple linear regression
      analysis was used to adjust for differences between groups. Median costs did not
      differ between sites ($126.30 for usual care and $88.10 for retail, P = 0.139);
      mean cost ranks were 132.5 for usual care and 115.6 for retail (P = 0.088). After
      adjusting for previous visit history, age, and sex, patients who received care in
      the retail setting had lower standard costs and lower cost rank than patients who
      received usual care (b = -52.9 [P = 0.006] and b = -24.5 [P = 0.021],
      respectively). After selection of cases with common conditions and adjustment for
      unequal variances, age, sex, and number of office visits in the previous 6
      months, our retail clinic appeared to reduce medical costs for patients during
      the 6-month period after the index visit.

PMID- 20038260
TI  - Is disease management right for oncology?
AB  - The disease management (DM) model for the treatment of chronic conditions has
      been around for many years and has been found to be effective for diseases of
      high prevalence and high cost (eg, diabetes, asthma, heart disease). With an
      increasing number of people living with cancer and the continual escalation of
      treatment costs, DM vendors have begun to implement DM concepts into cancer care.
      However, the multitude of cancer types, treatment options, and adverse effects
      have all presented barriers to oncology DM, and data reflecting the effectiveness
      of oncology DM have remained scarce. Oncology costs, the lack of congruence
      between provider and patient expectations of treatment, the lack of prevention
      and early detection for many cancers, and, most importantly, the inability of
      people to adhere to healthy lifestyles are additional obstacles that must be
      overcome. Moreover, when designing an oncology DM program, it is imperative to
      look at cancers individually as the etiology, treatment, and impact of cancer can
      be markedly different from one patient to the next. An effective oncology DM
      program is one that acts to decrease fatigue, reduces nosocomial infections,
      deals with dehydration and pain, manages anemia, identifies and treats skin
      infections, recognizes and treats depression and other psychological distress,
      provides patients access to palliative care services, facilitates informed
      decision making and end-of-life transitions, and promotes communication between
      patients and their providers as well as between physicians. Moving forward, DM
      vendors and health insurance companies capable of incorporating DM with medical
      management will be in the best position to provide optimal cancer care.

PMID- 20038261
TI  - Challenges and opportunities for using administrative data to explore changes in
      health status: a study of the closure of the Newfoundland cod fishery.
AB  - The closure of the cod fishery in Newfoundland and Labrador has had dramatic
      social and economic impacts on fishing communities in the province. Following a
      limited closure in 1992, a more extensive closure followed in 1994, which is
      still in force today, although income support provided to displaced fishery
      workers ended in 1999. A population-based study was conducted in 2004/2005 using
      7 different sources of administrative and survey data to investigate a range of
      social, demographic, and health changes in fishing communities affected by the
      closure of the cod fishery from the period 1991 to 2001. Findings of this study
      extend our understanding of the impact of the fishing moratorium in Newfoundland.
      This article also presents both the challenges to and opportunities for using
      administrative and survey data to explore the impact of the fishery closure on
      the health and well-being of Newfoundland fishing communities. One of the most
      significant challenges to using administrative and survey databases was the
      inconsistencies in how communities were identified across the various databases.
      Although not without limitations, administrative data is a cost-effective means
      to explore the impact of socioeconomic change on a population's health status.

PMID- 20038262
TI  - Effectiveness of acupuncture in the treatment of temporomandibular disorders of
      muscular origin: a systematic review of the last decade.
AB  - OBJECTIVE: The purpose of this review is to evaluate the effectiveness of using
      acupuncture treatment for temporomandibular disorders (TMD) of muscular origin
      according to research published in the last decade. METHODS: The information was
      gathered using the MEDLINE, EMBASE, CINAHL, and CISCOM databases. The inclusion
      criteria for selecting the studies were the following: (1) only randomized
      controlled trials (RCTs) were selected; (2) studies had to be carried out on
      patients with TMD of muscular origin; (3) studies had to use acupuncture
      treatment; and (4) studies had to be published in scientific journals between
      1997 and 2008. Two (2) independent reviewers analyzed the methodological quality
      of the studies using the Delphi list. A total of four RCTs were chosen once the
      methodological quality was judged as being acceptable. All of the studies
      included in the review compared the acupuncture treatment with a placebo
      treatment. All of them described results that were statistically significant in
      relation to short-term improvement of TMD signs and symptoms of a muscular
      origin, except one of the analyzed studies that found no significant difference
      between acupuncture and sham acupuncture. CONCLUSIONS: In the authors' opinion,
      research into the long-term effects of acupuncture in the treatment of TMD is
      needed. We also recommend larger samples sizes for future studies, so the results
      will be more reliable.

PMID- 20038263
TI  - Safety of intravenous methylprednisolone therapy in patients suffering from
      systemic sclerosis.

PMID- 20038264
TI  - AccessScope project: Accessible light microscope for users with upper limb
      mobility or visual impairments.
AB  - PURPOSE: A web-based application was developed to remotely view slide specimens
      and control all functions of a research-level light microscopy workstation,
      called AccessScope. Students and scientists with upper limb mobility and visual
      impairments are often unable to use a light microscope by themselves and must
      depend on others in its operation. METHOD: Users with upper limb mobility
      impairments and low vision were recruited to assist in the design process of the
      AccessScope personal computer (PC) user interface. Participants with these
      disabilities were evaluated in their ability to use AccessScope to perform
      microscopical tasks. AccessScope usage was compared with inspecting prescanned
      slide images by grading participants' identification and understanding of
      histological features and knowledge of microscope operation. RESULTS: With
      AccessScope subjects were able to independently perform common light microscopy
      functions through an Internet browser by employing different PC pointing devices
      or accessibility software according to individual abilities. Subjects answered
      more histology and microscope usage questions correctly after first participating
      in an AccessScope test session. CONCLUSIONS: AccessScope allowed users with upper
      limb or visual impairments to successfully perform light microscopy without
      assistance. This unprecedented capability is crucial for students and scientists
      with disabilities to perform laboratory coursework or microscope-based research
      and pursue science, technology, engineering, and mathematics fields.

PMID- 20038266
TI  - Development of mucoadhesive poly(lactide-co-glycolide) nanoparticles for ocular
      application.
AB  - Pilocarpine loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were
      prepared by solvent evaporation method and coated with various mucoadhesive
      polymers, in particular chitosan, sodium alginate and poloxamers. The size of
      chitosan-coated nanoparticles was larger than the size of all the other particles
      obtained. Their surface charge was changed from negative (-22.8 mV) to positive
      (+61.0 mV). The interaction between mucin and chitosan-coated nanoparticles took
      place up to six hours according to turbidimetric study. The positive charge of
      chitosan-coated nanoparticles decreased significantly six hours after incubation
      in mucin dispersion, which was attributed to their electrostatic interaction. The
      coating with chitosan could be considered useful approach aiming to prolong
      nanoparticle residence time after local ocular application.

PMID- 20038265
TI  - Metformin regulates palmitate-induced apoptosis and ER stress response in HepG2
      liver cells.
AB  - The excessive supply of fatty acids to the liver contributes to hepatic insulin
      resistance and endoplasmic reticulum (ER) stress associated with obesity or type
      2 diabetes mellitus. Furthermore, excess and/or prolonged ER stress contributes
      to hepatic cell death deteriorating nonalcoholic fatty liver disease to
      steatohepatitis. The aim of this study was to investigate the effects of
      metformin on palmitate-induced ER stress and hepatic insulin resistance in HepG2
      cells. Metformin significantly inhibited palmitate-induced cell death and
      apoptosis via caspase-3 activation. Metformin also blocked the induction of ER
      stress proteins (GRP78, Chop, Cleaved ATF-6, p-eIF2 alpha and XBP-1) and
      regulated serine phosphorylation of IRS-1. Metformin may therefore protect
      hepatocytes from death induced by saturated fatty acids. These data may also
      provide a further rationale for exploring the use of metformin in the treatment
      of non-alcoholic fatty liver disease, revealing its blocking effect for hepatic
      insulin resistance evoked by saturated fatty acids.

PMID- 20038267
TI  - Nicolau syndrome and perforator vessels: a new viewpoint for an old problem.
AB  - Nicolau syndrome is rare cutaneous adverse reaction following injection of
      various drugs. The disease has been associated with almost all classes of
      medications, such as nonsteroidal anti-inflammatory drugs, local anesthetics,
      corticosteroids, antibiotics, vitamin B complexes, antihistamines, and vaccines.
      The most severe cases of this complication occur after injection of nonsteroidal
      anti-inflammatory drugs. Subcutaneous injection is an important factor in the
      pathogenesis of the syndrome. We report a case of Nicolau syndrome resulting from
      intramuscular injection of diclofenac and discuss some precautions to prevent
      this complication.

PMID- 20038268
TI  - Chronic lymphocytic leukemia can cause acute renal failure even in early stage
      patients.

PMID- 20038270
TI  - Low-dose melphalan in myelodysplastic syndromes: an effective treatment for
      elderly RAEB-I or II patients?

PMID- 20038271
TI  - Synthesis and biological evaluation of some novel 6-aryl-2-(p-sulfamylphenyl)-4,5
      dihydropyridazin-3(2H)-ones as anti-cancer, antimicrobial, and anti-inflammatory
      agents.
AB  - A series of 6-aryl-2-(p-sulfamylphenyl)-4,5-dihydropyridazin-3(2H)-ones (2a-j)
      were synthesized by condensation of the appropriate beta-aroylpropionic acid and
      4-hydrazinobenzenesulfonamide hydrochloride in ethanol and tested for anti
      cancer, anti-inflammatory, and antimicrobial actions. According to the protocol
      of the National Cancer Institute (NCI) in vitro disease-oriented human cells
      screening panel assay, compound 2g showed high activity against HL-60 (TB)
      (leukemia), SR (leukemia), NCI-H522 (non-small-cell lung cancer), and BT-549
      (breast cancer) with a GI(50) value of less than 2 microM. Two compounds (2c and
      2f) were found to have promising anti-inflammatory activity, while a fair number
      of compounds showed good antifungal activity.

PMID- 20038272
TI  - Preclinical pharmacokinetics of KBF611, a new antituberculosis agent in mice and
      rabbits, and comparison with thiacetazone.
AB  - Thiacetazone (TAZ), one of the oldest known antituberculosis drugs, causes severe
      skin reactions in patients co-infected with tuberculosis and human
      immunodeficiency virus (HIV). KBF611 is a new fluorinated thiacetazone analogue
      that has shown strong antituberculosis effects. In order to provide valuable
      information for subsequent preclinical development, pharmacokinetics of KBF611
      and its analogue (TAZ) were studied and compared in two animal species (mice and
      rabbits) following intravenous and oral administration, and pharmacokinetic
      parameters were characterized. According to the calculated parameters, KBF611
      showed a more favourable pharmacokinetics profile than TAZ in terms of half-life
      (0.89 h compared with 0.57 in mice, p < 0.05, and 2.71 compared with 0.98 in
      rabbits, p < 0.001) and volume of distribution (1.45 l kg(-1) compared with 0.86
      l kg(-1) in mice, p < 0.05, and 1.01 l kg(-1) compared with 0.41 l kg(-1) in
      rabbits, p < 0.001) for tuberculosis therapy. In rabbits, the oral
      bioavailability of KBF611 was markedly lower than mice (39% compared with 82%),
      which may be attributed to a higher presystemic metabolism in rabbit liver. The
      results of in vivo studies on the metabolism of KBF611, supported by liquid
      chromatography-mass spectrometry (LC-MS) analysis, showed that the incorporation
      of a fluorine atom to the TAZ structure made the molecule susceptible to N
      deacetylation, a pathway not seen in TAZ metabolism. In summary, KBF611 could be
      considered a suitable candidate for further preclinical and clinical evaluation.

PMID- 20038269
TI  - Osteoblastogenesis and tumor growth in myeloma.
AB  - Myeloma is associated with suppression of osteoblastogenesis, consequentially
      resulting in increased osteoclast activity and induction of typical osteolytic
      bone disease. The molecular mechanisms by which myeloma cells suppress
      osteoblastogenesis and the consequences of increased osteoblast activity on
      myeloma cell growth have been partially delineated only recently. Reduced
      osteoblastogenesis is a consequence of abnormal properties and impaired
      osteogenic potential of osteoprogenitor cells from myeloma patients and is also
      the result of production of multiple osteoblastogenesis inhibitors by myeloma
      cells and by microenvironmental cells within the myelomatous bone. Nevertheless,
      novel osteoblast-activating agents (e.g. proteasome inhibitor bortezomib) are
      capable of inducing bone formation in myeloma animal models and clinically. These
      agents induce increased osteoblast activity, often coupled with a concomitant
      reduction in osteoclastogenesis, that is strongly associated with reduced myeloma
      tumor burden. In vitro, osteoblasts, in contrast to osteoclasts, attenuate the
      growth of myeloma cells from a large subset of patients; potential molecular
      mechanisms are discussed. These studies suggest that myeloma cells suppress
      osteoblastogenesis to their advantage and that increased osteoblast activity is a
      promising approach to treat myeloma bone disease and simultaneously control
      myeloma development and progression.

PMID- 20038273
TI  - Synthesis, characterization, DNA interaction, and cytotoxicity of novel Pd(II)
      and Pt(II) complexes.
AB  - Four complexes [Pd(L)(bipy)Cl].4H(2)O (1), [Pd(L)(phen)Cl].4H(2)O (2),
      [Pt(L)(bipy)Cl].4H(2)O (3), and [Pt(L)(phen)Cl].4H(2)O (4), where L = quinolinic
      acid, bipy = 2,2'-bipyridyl, and phen = 1,10-phenanthroline, have been
      synthesized and characterized using IR, (1)H NMR, elemental analysis, and single
      crystal X-ray diffractometry. The binding of the complexes to FS-DNA was
      investigated by electronic absorption titration and fluorescence spectroscopy.
      The results indicate that the complexes bind to FS-DNA in an intercalative mode
      and the intrinsic binding constants K of the title complexes with FS-DNA are
      about 3.5 x 10(4) M(-1), 3.9 x 10(4) M(-1), 6.1 x 10(4) M(-1), and 1.4 x 10(5) M(
      1), respectively. Also, the four complexes bind to DNA with different binding
      affinities, in descending order: complex 4, complex 3, complex 2, complex 1. Gel
      electrophoresis assay demonstrated the ability of the Pt(II) complexes to cleave
      pBR322 plasmid DNA.

PMID- 20038274
TI  - [Effect of myocardial revascularization on dynamics of factors of angiogenesis in
      patients with ischemic heart disease].
AB  - Aim of the study was to assess effect of myocardial revascularization on levels
      of factors of angiogenesis in early and remote period after intervention. Main
      group comprised 228 patients with ischemic heart disease (n=228, 194 men, 34
      women, mean age 57+/-8.7 years). Coronary bypass surgery was carried out in 29
      patients while other 199 were subjected to percutaneous coronary intervention
      (PCI). Analysis of data was performed in the group as a whole and in 2 subgroups
      distinguished in dependence on type of invasive treatment. Levels of factors of
      angiogenesis - vascular endothelial growth factor (VEGF), transforming growth
      factor beta (TGFbeta), and endostatin - were measured before, in 6 days, and 6
      months after invasive treatment. Compared with healthy persons patients with IHD
      had significantly higher level of VEGF and significantly lower levels of TGFbeta
      and endostatin. On day 6 after revascularization in the group as a whole level of
      VEGF insignificantly rose while level of TGFbeta insignificantly decreased. In 6
      months after invasive treatment significant lowering of VEGF level and
      significant increase of TGFbeta was noted. Endostatin level was measured at
      baseline and in 6 months after invasive treatment. Significant elevation of
      endostatin level took place after 6 months. Thus PCI and coronary bypass surgery
      lead to lowering of VEGF level and elevation of levels of TGFbeta in 6 days after
      intervention. In remote period reverse dynamics was observed: of VEGF level rose
      and those of TGFbeta and endostatin increased.

PMID- 20038275
TI  - [Effect of arterial stiffness on development of cardio-vascular complications in
      ischemic heart disease].
AB  - With the aim to assess effect of arterial wall stiffness on prognosis of patients
      with stable form of ischemic heart disease (IHD) we included 224 men (mean age
      56.2+/-8.9 years) with confirmed IND in a long-term prospective study. Pulse wave
      velocity was measured with brachial-ankle method (PWVba), presence of left
      ventricular hypertrophy (LVH) was detected with electrocardiography. Coronary
      arteriography was carried out in 126 patients. During 3.5 years of follow-up
      there were 38 cardiovascular complications (CVC) (6 myocardial infarctions, 19
      operations of revascularization, 11 hospitalizations because of unstable angina,
      3 sudden deaths). Patients were distributed to groups (tertiles) depending on
      PWVba values. Elevation of stiffness of arteries from lowest to highest tertile
      was significantly associated with increases of age, level of arterial pressure,
      heart rate, level of total cholesterol, LVH, severity and extent of coronary
      atherosclerosis. The Cox model of proportional risks comprising 14 main risk
      factors allowed to reveal that only PWVba significantly (<0.001) contributed to
      formation of prognosis. In patients with PWVba exceeding 14.3 m/s (highest
      tertile) compared with those with PWVba below 12.4 m/s (lowest tertile) risk of
      development of CVC was 4.23 times higher (5.27 times higher after adjustment for
      age and systolic arterial pressure). Comparison of Kaplan-Maier survival curves
      confirmed that in patients with low PWVba cumulative probability of absence of
      CVC was greater than in patients with higher stiffness of arterial wall (<0.008).
      PWVba as marker of arterial stiffness in men with chronic course of IHD appears
      to be predictor of CVC independent on age and classic risk factors.

PMID- 20038276
TI  - [Reactions of sympatho-adrenal system in patients with ischemic heart disease
      during emotional stress in dependence on the personality type].
AB  - The object of the study was to show the relationship between emotional stress and
      excitation of the sympathoadrenal system in healthy subjects and patients with
      coronary heart disease (CHD). Seventy eight healthy subjects and 40 CHD patients
      of the II-III functional class were under medical observation. Emotional tension
      was simulated by two methods: arithmetic under conditions of time deficit
      (Krepelin counting) and work in a homeostat. Homeostat simulation of emotional
      tension turned to be more stressogenic than Krepelin counting. In CHD patients,
      increase of adrenaline and noradrenaline levels was demonstrated in the condition
      of the emotional tension simulation. Two personality types were distinguished as
      type A (leaders) and type B (subordinates). The increase in the catecholamine
      level was especially pronounced in CHD patients of type A (leaders).

PMID- 20038277
TI  - [Phenotypes of arterial pressure in young men].
AB  - AIM: To study with the use of repetitive clinical measurements and 24-hour
      arterial pressure (AP) monitoring phenotypes of AP in young men aged 18-25 years
      with history of elevation of AP at accidental determination. MATERIAL AND
      METHODS: We examined 194 young men (mean age 21.1+/-2.1 years) because of
      detection of elevated AP at casual measurements. Clinical AP was assessed at
      repetitive determinations in sitting position at the same time on 5 consecutive
      days. 24-hour AP monitoring (24-HAPM) was carried out according to standard
      method. Classification of AP level and phenotype was made in accordance with
      recommendations of European Society of Arterial Hypertension (AH) (2007).
      RESULTS: Optimal clinical AP was found in 13 (6.7%), normal AP - in 20 (10.3%),
      high normal AP - in 24 (12,4%), stable AH - in 107 (55.2%) young men. Eighty one
      persons (41.8%) had I, 20 (10.3%) - II, and 6 (3.1%) - III degree AH. Among
      studied patients with stable elevation of clinical AP rate of isolated systolic
      AH (ISAH) was 65.4%, systole-diastolic AH - 6.1%, isolated diastolic AH - 8.4%.
      Comparison of levels of clinical AP and 24-HAPM showed that 34 young men (17.5%)
      had white coat hypertension, 73 (37.6%) - had true AH, 13 (6.7%) - concealed AH.
      The level of clinical SAP turned out to be the sole predictor of concealed AH.
      Among examined persons 40 (20.6%) had 1, 57 (29.4%) - 2, 34 (17.5%) - 3 or more
      additional risk factors. Sixty one subjects (31.4%) had metabolic syndrome. No
      association was established between number of risk factors, presence of metabolic
      syndrome, and AP phenotype. Left ventricular hypertrophy was revealed in 24.4% of
      patients with true AH and in 15.2% - with concealed AH. CONCLUSION: Dominating
      type of AH in young men is ISAH. The data obtained evidence for importance of 24
      HAPM for establishment of AP phenotype in young men with normal and high normal
      clinical AP.

PMID- 20038278
TI  - [Pharmacotherapy and analysis of the course of pregnancy and perinatal outcomes
      in women with hypertensive disease].

PMID- 20038279
TI  - [N-terminal pro-brain natriuretic peptide and cardiac involvement in patients
      with hypertensive disease].
AB  - The purpose of this study was to define a correlation between N-terminal proBNP
      level and extent of cardiac abnormalities. A total of 40 patients with
      hypertension were included in the study (60.5+/-7.6 years of age; 18 men, 22
      women). It was found that patients with hypertension had increased plasma N
      terminal proBNP level, that it increased with age and tended to be higher in
      patients with concentric hypertrophy compared with those with normal geometry and
      eccentric hypertrophy; however, the differences were not significant. N-terminal
      proBNP concentration depended on ventricular septal thickness and left
      ventricular wall thickness. Analysis of association between N-proBNP level and
      parameters of myocardial diastolic function showed that increased plasma peptide
      levels correlated with degree of diastolic dysfunction in patients with altered
      left ventricular relaxation.

PMID- 20038280
TI  - [Aorto-coronary bypass grafting in patients with pronounced left ventricular
      dysfunction: long-term results and value of detection of viable myocardium].
AB  - Aim of the study was to investigate effect of volume of viable myocardium as
      detected by stress-echocardiography on functional class and survival of patients
      with pronounced left ventricular dysfunction after aorto-coronary bypass grafting
      (ACBG). We made retrospective analysis of clinical and echocardiographic data
      from 216 patients with pronounced coronary pathology and left ventricular
      ejection fraction 35%. Stress echocardiography was carried out according to
      standard method in 70 patients. Mean duration of follow-up after ACBG was 2.5+/
      2.3 years (from 0.4 to 9 years). Complete revascularization eliminated symptoms
      of angina, improved functional class of patients and was associated with high
      survival (5-year - 85%, 7-year - 78%). No significant effect of volume of viable
      myocardium on functional class and survival of patients after ACBG was revealed.

PMID- 20038282
TI  - [Possibilities of testosterone in complex therapy of patients with dilated
      cardiomyopathy].

PMID- 20038281
TI  - [Effects of dinitrosyl iron complex on metabolism and cellular membranes in
      ischemic rat heart].
AB  - Effects of exogenous NO donor--dinitrosyl iron complex with reduced glutathione
      (DNIC-GS) on functional recovery of isolated perfused rat heart subjected to
      global ischemia and reperfusion have been studied. DNIC-GS administration after
      ischemia substantially improved contractile and pump function recovery within a
      concentration range of 34 nM - 5 uM. In case of DNIC-GS administration before
      ischemia a two-phase influence was found--cardioprotective action for 67 nM and
      damaging one for 250 nM. Enhanced recovery of cardiac function after preischemic
      infusion of 67 nM DNIC-GS was associated with augmented preservation of ATP,
      phosphocreatine, total adenine nucleotide pool and total creatine content in
      myocardial tissue, and with reduction of lactate dehydrogenase (LDH) release into
      myocardial effluent compared with these indices in control. In contrast, infusion
      of 250 nM DNIC-GS resulted in poor recovery of energy metabolism and increased
      membrane injury than in control. The results suggest that a worse recovery of
      myocardial energy state and increased sarcolemma permeability in the 250 nM DNIC
      GS group were caused by inhibiting oxidation of glucose, the main energy
      substrate for isolated perfused heart. Molecular mechanisms of protective and
      injurious action of DNIC-GS on ischemic heart are discussed.

PMID- 20038283
TI  - [Clinical study of arterial rigidity. Part II. Remodeling of vessels in arterial
      hypertension and metabolic syndrome. possibilities of correction with drugs].
AB  - In the second part of the review we present data on vascular remodeling in
      arterial hypertension and metabolic syndrome with analysis of factors and
      mechanisms influencing pulse wave propagation velocity in these diseases. We also
      consider possibilities of correction of remodeling of vessels with contemporary
      antihypertensive drugs.

PMID- 20038284
TI  - [Intravascular ultrasound investigation with virtual hystology in the study of
      coronary artery lesions].
AB  - Spectral analysis of radiofrequency data obtained at intravascular ultrasound
      study allows to carry out more detailed analysis and morphological assessment of
      plaque components. In the course of preliminary investigations in vitro 4 types
      of reflected signals were revealed. According to results of spectral analysis of
      radiofrequency data these signals correspond to histological plaque components.
      Color coding was assigned to various components (fibrotic, fibrolipid, necrotic
      core, and calcinosis). Based on cluster technique invasive diagnostic
      intravascular ultrasound study with virtual histology allows to identify plaques
      of different types. It has become possible to detect criteria of plaque
      vulnerability. At present criteria of increased vulnerability based on
      histopathological studies appear to be widening of necrotic core, presence of
      fibrous capsule, inclusions of calcinosis, positive remodeling of coronary
      vascular bed, degree of stenosis, and localization of lesion.

PMID- 20038285
TI  - [Thienopyridines in the treatment and prevention of cardiovascular diseases. III.
      therapeutic application of clopidogrel as monotherapy (without acetylsalicylic
      acid)].
AB  - In a series of articles the authors consider clinical pharmacology and experience
      of clinical application of blockers of platelet P2Y12 receptors, most well known
      representatives of which ticlopidine and clopidogrel according to chemical
      structure belong to thienopyridine derivatives. In the third communication we
      consider data of randomized studies in which efficacy and safety of clopidogrel
      monotherapy has been assessed in comparison with acetylsalicylic acid (ASA),
      ticlopidine, warfarin, as well as ASA in combination with extended release form
      of dipyridamole in various cardio-vascular diseases. Results of these studies
      indicate that efficacy of monotherapy with clopidogrel is comparable with that of
      ASA, ticlopidine, warfarin, and ASA in combination with extended release form of
      dipyridamole. Clopidogrel significantly more rarely causes ulcerogenic and other
      hemorrhagic complications than ticlopidine, but is substantially more expensive.
      Therefore prescribing of clopidogrel as monotherapy is justified only in those
      cases when ASA and ticlopidine are contraindicated or induce pronounced side
      effects.

PMID- 20038286
TI  - [Thienopyridines in the treatment and prevention of cardiovascular diseases. Part
      IV. therapeutic application of clopidogrel in combination with acetylsalicylic
      acid in acute coronary syndromes and percutaneous coronary interventions].
AB  - In a series of articles the authors consider clinical pharmacology and experience
      of clinical application of blockers of platelet P2Y12 receptors, most well known
      representatives of which ticlopidine and clopidogrel according to chemical
      structure belong to thienopyridine derivatives. In the forth communication we
      consider data of randomized studies in which efficacy and safety of clopidogrel
      in combination with has acetylsalicylic acid (ASA) been assessed in comparison
      with (ASA) in various acute coronary syndromes (ACS), as well as before, during,
      and after percutaneous coronary interventions (PCI). In ACS it is recommended to
      start therapy with clopidogrel with 300 mg loading dose with subsequent
      transition to maintenance dose 75 mg/day. Preliminary therapy with clopidogrel
      (in combination with ASA) before emergent or elective PCI significantly decreases
      risk of development of unfavorable clinical outcomes. In PCI loading dose of
      clopidogrel is 300-600 mg while duration of maintenance therapy (75 mg/day)
      depends on the type of used coronary stent. After implantation of bare stent
      duration of therapy with clopidogrel should be not less than 1 month (ideally no
      less that 12 months) and after implantation of drug-eluting stent - not less than
      12 months.

PMID- 20038287
TI  - [Determination of the cause of repetitive syncopal States with the help of
      registration of electrocardiogram at the background of provocative test].
AB  - A clinical case of repetitive syncopal states in an adolescent with episodes of
      significant asystoles lasting up to 32 s is presented. These episodes were
      detected only with the help of electrocardiogram registered during provocative
      test. Beyond provoking factors the child had signs of insignificant sinus node
      dysfunction which did not allow to designate the state of the patient as severe
      and prescribe adequate treatment. We consider this case as demonstration of
      necessity of provocative tests in conjunction with ECG monitoring in children
      with episodes of fainting (syncopal states).

PMID- 20038289
TI  - [How to treat elderly and gerontal patients with arterial hypertension].

PMID- 20038288
TI  - [Adipose tissue inflammation and atherosclerosis].
AB  - Adipose tissue is an endocrine organ secreting more than 30 various adipokines
      which regulate wide spectrum of metabolic and immune processes. Obesity is
      associated with development of adipose tissue inflammation. This inflammation is
      characterized by infiltration with macrophages, alterations of adipokine
      secretion, development of insulin resistance. All these factors promote
      atherosclerosis. Inflammation of perivascular adipose tissue is especially
      important. Adipokines damage vascular endothelium via paracrine pathway.
      Cytokines released by macrophages as well as changes of adipokine secretion lead
      to endothelial dysfunction - the first stage of atherogenesis. Besides specific
      action curative factors used in obesity, metabolic syndrome, and diabetes
      mellitus also produce anti-inflammatory effect and thus diminish risk factors of
      cardiovascular diseases, rate of their development, and alleviate manifestations
      of atherosclerosis. Inflammation of adipose tissue is a connecting link between
      obesity and atherosclerosis. This review contains an outline of roles of various
      major adipokines in development of atherosclerosis as well as synopsis of anti
      inflammatory and antiatherogenic effects of glytazones , metformin, rimonabant,
      statins, and of lowering of body weight.

PMID- 20038290
TI  - Amount of external CME in groups of specialties: a nation-wide survey among
      Finnish doctors.
AB  - BACKGROUND: Continuing medical education (CME) is an integral part of continuing
      professional development and a prerequisite for good quality in health care. We
      aimed to describe and analyse the number of days spent in formal CME outside the
      workplace by specialty among Finnish doctors of working age. FINDINGS: The number
      of days in formal CME outside the workplace in 2005 reported by specialists was
      obtained from an annual postal survey, conducted by the Finnish Medical
      Association in March 2006, of all working-age doctors. Those who had attained
      their specialist degree before 2005 were included in the study. The 49
      specialties were re-categorised into 15 groups. The mean reported number of days
      and 95% confidence intervals were calculated. Differences were analysed by
      Poisson regression adjusted for relevant covariates. The response rate to the
      question about CME was 70.2% (7,374) among specialists. The median age
      (interquartile range) of the respondents was 49 years (from 44 to 55 years), and
      51.7% (3,810) were female. The mean reported number of days in CME was 8.8 (95%
      CI 8.7-9.0). Neurologists and surgery specialists participated in CME the most
      frequently (10.3 and 10.4 days) and ophthalmologists the least (7.6 days). In
      comparison with anaesthesiology and intensive care specialists, most specialists
      reported having significantly more formal CME, and no group reported having less.
      CONCLUSIONS: Significant variation was observed, and we therefore suggest studies
      seeking to account for this variation. The results have originally been published
      in Finnish in the Finnish Medical Journal.

PMID- 20038291
TI  - Discriminating the native structure from decoys using scoring functions based on
      the residue packing in globular proteins.
AB  - BACKGROUND: Setting the rules for the identification of a stable conformation of
      a protein is of utmost importance for the efficient generation of structures in
      computer simulation. For structure prediction, a considerable number of possible
      models are generated from which the best model has to be selected. RESULTS: Two
      scoring functions, Rs and Rp, based on the consideration of packing of residues,
      which indicate if the conformation of an amino acid sequence is native-like, are
      presented. These are defined using the solvent accessible surface area (ASA) and
      the partner number (PN) (other residues that are within 4.5 A) of a particular
      residue. The two functions evaluate the deviation from the average packing
      properties (ASA or PN) of all residues in a polypeptide chain corresponding to a
      model of its three-dimensional structure. While simple in concept and
      computationally less intensive, both the functions are at least as efficient as
      any other energy functions in discriminating the native structure from decoys in
      a large number of standard decoy sets, as well as on models submitted for the
      targets of CASP7. Rs appears to be slightly more effective than Rp, as determined
      by the number of times the native structure possesses the minimum value for the
      function and its separation from the average value for the decoys. CONCLUSION:
      Two parameters, Rs and Rp, are discussed that can very efficiently recognize the
      native fold for a sequence from an ensemble of decoy structures. Unlike many
      other algorithms that rely on the use of composite scoring function, these are
      based on a single parameter, viz., the accessible surface area (or the number of
      residues in contact), but still able to capture the essential attribute of the
      native fold.

PMID- 20038292
TI  - Molecular evolution of the pDo500 satellite DNA family in Dolichopoda cave
      crickets (Rhaphidophoridae).
AB  - BACKGROUND: Non-coding satellite DNA (satDNA) usually has a high turn-over rate
      frequently leading to species specific patterns. However, some satDNA families
      evolve more slowly and can be found in several related species. Here, we analyzed
      the mode of evolution of the pDo500 satDNA family of Dolichopoda cave crickets.
      In addition, we discuss the potential of slowly evolving satDNAs as phylogenetic
      markers. RESULTS: We sequenced 199 genomic or PCR amplified satDNA repeats of the
      pDo500 family from 12 Dolichopoda species. For the 38 populations under study, 39
      pDo500 consensus sequences were deduced. Phylogenetic analyses using Bayesian,
      Maximum Parsimony, and Maximum Likelihood approaches yielded largely congruent
      tree topologies. The vast majority of pDo500 sequences grouped according to
      species designation. Scatter plots and statistical tests revealed a significant
      correlation between genetic distances for satDNA and mitochondrial DNA. Sliding
      window analyses showed species specific patterns of variable and conserved
      regions. The evolutionary rate of the pDo500 satDNA was estimated to be 1.63
      1.78% per lineage per million years. CONCLUSIONS: The pDo500 satDNA evolves
      gradually at a rate that is only slightly faster than previously published rates
      of insect mitochondrial COI sequences. The pDo500 phylogeny was basically
      congruent with the previously published mtDNA phylogenies. Accordingly, the
      slowly evolving pDo500 satDNA family is indeed informative as a phylogenetic
      marker.

PMID- 20038293
TI  - Restoration of contact inhibition in human glioblastoma cell lines after MIF
      knockdown.
AB  - BACKGROUND: Studies of the role of the cytokine macrophage-migration-inhibitory
      factor (MIF) in malignant tumors have revealed its stimulating influence on cell
      cycle progression, angiogenesis and anti-apoptosis. RESULTS: Here we show that in
      vitro targeting MIF in cultures of human malignant glioblastoma cells by either
      antisense plasmid introduction or anti-MIF antibody treatment reduced the growth
      rates of tumor cells. Of note is the marked decrease of proliferation under
      confluent and over-confluent conditions, implying a role of MIF in overcoming
      contact inhibition. Several proteins involved in contact inhibition including
      p27, p21, p53 and CEBPalpha are upregulated in the MIF antisense clones
      indicating a restoration of contact inhibition in the tumor cells.
      Correspondingly, we observed a marked increase in MIF mRNA and protein content
      under higher cell densities in LN18 cells. Furthermore, we showed the relevance
      of the enzymatic active site of MIF for the proliferation of glioblastoma cells
      by using the MIF-tautomerase inhibitor ISO-1. CONCLUSION: Our study adds another
      puzzle stone to the role of MIF in tumor growth and progression by showing the
      importance of MIF for overcoming contact inhibition.

PMID- 20038294
TI  - A survey on worries of pregnant women--testing the German version of the
      Cambridge worry scale.
AB  - BACKGROUND: Pregnancy is a transition period in a woman's life characterized by
      increased worries and anxiety. The Cambridge Worry Scale (CWS) was developed to
      assess the content and extent of maternal worries in pregnancy. It has been
      increasingly used in studies over recent years. However, a German version has not
      yet been developed and validated.The aim of this study was (1) to assess the
      extent and content of worries in pregnancy on a sample of women in Germany using
      a translated and adapted version of the Cambridge Worry Scale, and (2) to
      evaluate the psychometric properties of the German version. METHODS: We conducted
      a cross-sectional study and enrolled 344 pregnant women in the federal state of
      Baden-Wurttemberg, Germany. Women filled out structured questionnaires that
      contained the CWS, the Spielberger-State-Trait-Anxiety Inventory (STAI), as well
      as questions on their obstetric history. Antenatal records were also analyzed.
      RESULTS: The CWS was well understood and easy to fill in. The major worries
      referred to the process of giving birth (CWS mean value 2.26) and the possibility
      that something might be wrong with the baby (1.99), followed by coping with the
      new baby (1.57), going to hospital (1.29) and the possibility of going into
      labour too early (1.28). The internal consistency of the scale (0.80) was
      satisfactory, and we found a four-factor structure, similar to previous studies.
      Tests of convergent validity showed that the German CWS represents a different
      construct compared with state and trait anxiety but has the desired overlap.
      CONCLUSIONS: The German CWS has satisfactory psychometric properties. It
      represents a valuable tool for use in scientific studies and is likely to be
      useful also to clinicians.

PMID- 20038296
TI  - Reconstructing nonlinear dynamic models of gene regulation using stochastic
      sampling.
AB  - BACKGROUND: The reconstruction of gene regulatory networks from time series gene
      expression data is one of the most difficult problems in systems biology. This is
      due to several reasons, among them the combinatorial explosion of possible
      network topologies, limited information content of the experimental data with
      high levels of noise, and the complexity of gene regulation at the
      transcriptional, translational and post-translational levels. At the same time,
      quantitative, dynamic models, ideally with probability distributions over model
      topologies and parameters, are highly desirable. RESULTS: We present a novel
      approach to infer such models from data, based on nonlinear differential
      equations, which we embed into a stochastic Bayesian framework. We thus address
      both the stochasticity of experimental data and the need for quantitative dynamic
      models. Furthermore, the Bayesian framework allows it to easily integrate prior
      knowledge into the inference process. Using stochastic sampling from the Bayes'
      posterior distribution, our approach can infer different likely network
      topologies and model parameters along with their respective probabilities from
      given data. We evaluate our approach on simulated data and the challenge #3 data
      from the DREAM 2 initiative. On the simulated data, we study effects of different
      levels of noise and dataset sizes. Results on real data show that the dynamics
      and main regulatory interactions are correctly reconstructed. CONCLUSIONS: Our
      approach combines dynamic modeling using differential equations with a stochastic
      learning framework, thus bridging the gap between biophysical modeling and
      stochastic inference approaches. Results show that the method can reap the
      advantages of both worlds, and allows the reconstruction of biophysically
      accurate dynamic models from noisy data. In addition, the stochastic learning
      framework used permits the computation of probability distributions over models
      and model parameters, which holds interesting prospects for experimental design
      purposes.

PMID- 20038295
TI  - Divergence of allosteric effects of rapacuronium on binding and function of
      muscarinic receptors.
AB  - BACKGROUND: Many neuromuscular blockers act as negative allosteric modulators of
      muscarinic acetylcholine receptors by decreasing affinity and potency of
      acetylcholine. The neuromuscular blocker rapacuronium has been shown to have
      facilitatory effects at muscarinic receptors leading to bronchospasm. We examined
      the influence of rapacuronium on acetylcholine (ACh) binding to and activation of
      individual subtypes of muscarinic receptors expressed in Chinese hamster ovary
      cells to determine its receptor selectivity. RESULTS: At equilibrium rapacuronium
      bound to all subtypes of muscarinic receptors with micromolar affinity (2.7-17
      microM) and displayed negative cooperativity with both high- and low-affinity ACh
      binding states. Rapacuronium accelerated [3H]ACh association with and
      dissociation from odd-numbered receptor subtypes. With respect to [35S]GTPgammaS
      binding rapacuronium alone behaved as an inverse agonist at all subtypes.
      Rapacuronium concentration-dependently decreased the potency of ACh-induced
      [35S]GTPgammaS binding at M2 and M4 receptors. In contrast, 0.1 microM
      rapacuronium significantly increased ACh potency at M1, M3, and M5 receptors.
      Kinetic measurements at M3 receptors showed acceleration of the rate of ACh
      induced [35S]GTPgammaS binding by rapacuronium. CONCLUSIONS: Our data demonstrate
      a novel dichotomy in rapacuronium effects at odd-numbered muscarinic receptors.
      Rapacuronium accelerates the rate of ACh binding but decreases its affinity under
      equilibrium conditions. This results in potentiation of receptor activation at
      low concentrations of rapacuronium (1 microM) but not at high concentrations (10
      microM). These observations highlight the relevance and necessity of performing
      physiological tests under non-equilibrium conditions in evaluating the functional
      effects of allosteric modulators at muscarinic receptors. They also provide
      molecular basis for potentiating M3 receptor-mediated bronchoconstriction.

PMID- 20038297
TI  - Digestibility of Duddingtonia flagrans chlamydospores in ruminants: in vitro and
      in vivo studies.
AB  - BACKGROUND: The use of Duddingtonia flagrans as a tool for the biological control
      of gastrointestinal nematodes (GIN) is a promising alternative to anthelmintics.
      The chlamydospores of D. flagrans are orally dosed and their thick cell wall
      gives them the capacity to resist digestion and pass through the gastrointestinal
      tract (GIT). Chlamydospores reaching the faeces are able to germinate and trap
      nematode larvae. The efficacy of this control method is based on reducing the
      numbers of infective larvae leaving the faeces. Techniques have recently been
      developed for quantifying the numbers of chlamydospores in faeces. As the number
      of non-digested spores could be relevant in the design and optimization of dosing
      programmes for the control of GIN infective larvae, the aim of the present study
      was to estimate the loss of D. flagrans chlamydospores during their passage
      through the ruminant gastrointestinal tract using in vitro and in vivo
      techniques. RESULTS: After in vitro rumen digestion, chlamydospore recovery was
      not different from the quantity originally incubated (undigested spores) (P >
      0.05). In vitro rumen+abomasum digestion caused nearly 36% loss of the
      chlamydospores originally incubated (P < 0.05). Germination of chlamydospores
      classified as viable was 24.3%. Chlamydospores classified as non-viable did not
      germinate. Rumen digestion resulted in more spore germination (R1 = 35.7% and R2
      = 53.3%) compared to no digestion (time 0 h = 8.7%). Subsequent abomasal
      digestion reduced germination (R1+A = 25%) or stopped it (R2+A = 0%). In vivo
      apparent chlamydospore digestibility in sheep showed a loss of 89.7% of the
      chlamydospores (P < 0.05). CONCLUSIONS: The loss of chlamydospores was evident
      under in vitro and in vivo conditions. Negligible amounts of spores were lost
      during the in vitro rumen digestion. However, in vitro rumen+abomasum digestion
      resulted in a chlamydospore loss of approximately 36%. In vivo passage through
      the sheep GIT resulted in a total loss of 89.7% of the orally administered
      spores.

PMID- 20038298
TI  - Evidence and rationale for the World Health Organization recommended standards
      for Japanese encephalitis surveillance.
AB  - BACKGROUND: Japanese encephalitis (JE) is the most important form of viral
      encephalitis in Asia. Surveillance for the disease in many countries has been
      limited. To improve collection of accurate surveillance data in order to increase
      understanding of the full impact of JE and monitor control programs, World Health
      Organization (WHO) Recommended Standards for JE Surveillance have been developed.
      To aid acceptance of the Standards, we describe the process of development,
      provide the supporting evidence, and explain the rationale for the
      recommendations made in the document. METHODS: A JE Core Working Group was formed
      in 2002 and worked on development of JE surveillance standards. A series of
      questions on specific topics was initially developed. A literature review was
      undertaken and the findings were discussed and documented. The group then
      prepared a draft document, with emphasis placed on the feasibility of
      implementation in Asian countries. A field test version of the Standards was
      published by WHO in January 2006. Feedback was then sought from countries that
      piloted the Standards and from public health professionals in forums and
      individual meetings to modify the Standards accordingly. RESULTS: After
      revisions, a final version of the JE surveillance standards was published in
      August 2008. The supporting information is presented here together with
      explanations of the rationale and levels of evidence for specific
      recommendations. CONCLUSION: Provision of the supporting evidence and rationale
      should help to facilitate successful implementation of the JE surveillance
      standards in JE-endemic countries which will in turn enable better understanding
      of disease burden and the impact of control programs.

PMID- 20038299
TI  - Malaria in infants below six months of age: retrospective surveillance of
      hospital admission records in Blantyre, Malawi.
AB  - BACKGROUND: Information on the burden of malaria in early infancy is scarce.
      Young infants are relatively protected against clinical malaria during the first
      six months of life due to the presence of maternal antibodies and foetal
      haemoglobin, and have received relatively little attention with respect to
      research and treatment guidelines. The World Health Organization provides
      treatment guidelines for children from six months onwards, without specific
      treatment guidelines for the younger infants. A number of recent reports however
      suggest that the burden in this young age group may be underestimated. METHODS: A
      retrospective review of paediatric hospital records at the Queen Elizabeth
      Central Hospital in Blantyre from 1998 to 2008 from three data sources was
      carried out. The number of admitted infants < 6 months and < or = 15 years was
      obtained from the registry books of the Paediatric-Nursery-Department and the
      Malaria Research Laboratory. For the period 2001-2004, more detailed malaria
      related admission information was available as part of an ongoing study on severe
      malaria, allowing a calculation of the proportion of infants < 6 months of age
      among admissions in children < 5 years. RESULTS: Retrospective analysis of
      hospital records showed that over the course of these years, the average annual
      proportion of paediatric admissions in children < or = 15 years with confirmed
      malaria aged < 6 months was 4.8% and ranged between 2.8%-6.7%. This proportion
      was stable throughout the seasons. Between 2001-2004, 9.9% of admissions with
      confirmed malaria in children < 5 years occurred in infants < 6 months, with
      numbers increasing steadily during the first six months of life. CONCLUSIONS:
      These findings are consistent with recent reports suggesting that the burden of
      malaria during the six first months of life may be substantial, and highlight
      that more research is needed on dose-optimization, safety and efficacy of anti
      malarials that are currently used off-label in this vulnerable patient group.

PMID- 20038300
TI  - Articular cartilage mineralization in osteoarthritis of the hip.
AB  - BACKGROUND: The aim of this study was to examine the frequency of articular
      cartilage calcification in patients with end-stage hip OA. Further, its impact on
      the clinical situation and the OA severity are analyzed. METHODS: Eighty patients
      with OA of the hip who consecutively underwent total hip replacement were
      prospectively evaluated, and 10 controls were included. The patients' X-rays were
      analyzed for the presence of articular cartilage mineralization. A Harris Hip
      Score (HHS) was preoperatively calculated for every patient.Slab specimens from
      the femoral head of bone and cartilage and an additional square centimeter of
      articular cartilage from the main chondral defect were obtained from each patient
      for analysis of mineralization by digital contact radiography (DCR). Histological
      grading was also performed. In a subset of 20 patients, minerals were
      characterized with an electron microscope (FE-SEM). RESULTS: Calcifications were
      seen in all OA cartilage and slab specimens using DCR, while preoperative X-rays
      revealed calcification in only 17.5%. None of the control cartilage specimens
      showed mineralization. There was a highly significant inverse correlation between
      articular cartilage calcification and preoperative HHS. Histological OA grade
      correlated positively with the amount of matrix calcification. FE-SEM analysis
      revealed basic calcium phosphate (BCP) as the predominant mineral; CPPD crystals
      were found in only two patients. CONCLUSIONS: Articular cartilage calcification
      is a common event in osteoarthritis of the hip. The amount of calcification
      correlates with clinical symptoms and histological OA grade.

PMID- 20038301
TI  - [Perspective of cervical cancer prevention and control in developing countries
      and areas].
AB  - Cervical cancer ranks the second common cancer in women, affecting women severely
      in developing countries. It is a critical issue to develop simple, rapid,
      accurate, safe, acceptable, and inexpensive screening tests which can be used in
      cervical cancer prevention programs in developing countries. Due to the shortage
      of funding and qualified cytological professionals in most developing countries,
      WHO has been actively promoting visual inspection with acetic acid/iodine
      solution (VIA/VILI) as the alternative approach to screening cervical cancer.
      After the discovery of a link between human papillomavirus (HPV) and cervical
      cancer, the HPV prophylactic vaccine and CareHPV test have been successfully
      developed. The cervical cancer will be the first cancer eliminated by the
      combination of vaccination, screening, early diagnosis and treatment.

PMID- 20038302
TI  - [Three-year follow-up results of visual inspection with acetic acid/Lugol's
      iodine (VIA/VILI) used as an alternative screening method for cervical cancer in
      rural areas].
AB  - BACKGROUND AND OBJECTIVE: In China, there has been no established national
      program for cervical cancer prevention, the screening methods and experiences are
      especially deficient in the rural areas. The aim of this paper is to evaluate the
      effects of acetic acid/Lugol's iodine (VIA/VILI) used for screening of cervical
      cancer and pre-cancerous lesions in a rural area of China by analyzing the large
      scale population-based screening data from the demonstration site. METHODS: Women
      aged 30-59 years from Xiangyuan County in Shanxi Province were recruited for
      cervical cancer screening from 2005 to 2007. VIA/VILI was the primary screening
      method followed by colposcopy if the VIA/VILI was positive. Cervical lesions were
      diagnosed by directed biopsy under the colposcopy. The VIA/VILI negative women or
      cervical intraepithelial neoplasia 1 (CIN1) were re-screened using the same
      procedure in the next year. RESULTS: In total, 7145 women received the cervical
      cancer screening, with a participation rate of 74.75%. Their average age was
      42.16 years. A total of 1287 women were consecutively screened for three times
      from 2005 to 2007. The detection rates of CIN2, CIN3 and cervical cancer were
      0.70% (9/1287), 1.01% (13/1287) and 0.23% (3/1287) for the first round screening,
      and were 0.22% (2/976), 0.11% (1/976) and 0% (0/976) for the second round
      screening, respectively. Only one CIN2 was found in the third round screening. In
      the years of 2006-2007, 3490 women were screened consecutively twice. The
      detection rates of CIN2, CIN3 and cervical cancer were 0.26% (9/3490), 0.52%
      (18/3490) and 0.15% (5/3490) for the first round screening, and 0.40% (14/2943),
      0.40% (14/2943) and 0.03% (1/2943) for the second round screening. Likewise, 2
      368 women were screened consecutively twice in the years of 2007-2008. The
      detection rates of CIN2, CIN3 and cervical cancer were 0.55% (13/2368), 0.25%
      (6/2368) and 0.12% (3/2368) for the first round screening, and 0.42 (10/2040),
      0.04% (1/2040) and 0% for the second round screening. The cumulative detection
      rates for CIN2, CIN3 and cervical cancer were 0.81% (58/7145), 0.74% (53/7145)
      and 0.17% (12/7145), respectively. And 53.45% (31/58) of CIN2, 68.81% (37/53) of
      CIN3 and almost all cervical cancers (11/12) were found during the first round
      screening, except for an early stage cervical cancer (Ia). Only one CIN2 was
      detected in the third round screening in the same population. The average age of
      CIN1, CIN2, CIN3 and cervical cancer were 38.65, 40.61, 44.10 and 46.73 years,
      respectively. CONCLUSIONS: VIA/VILI can be used as an alternative screening
      method for cervical cancer and high-grade pre-cancerous lesions among the women
      aged 30-59 years in China's rural areas because of its low cost, easy training
      for the local health providers, and less depending on facilities. One round
      screening by VIA/VILI can detect more than a half of CIN2, two-thirds of CIN3 and
      almost all the cervical cancer in the population, and the detection rates of
      CIN2/3 can be increased by two consecutive rounds of screening.

PMID- 20038303
TI  - [Inhibiting effect of letrozole combined with curcumin on xenografted endometrial
      carcinoma growth in nude mice].
AB  - BACKGROUND AND OBJECTIVE: Letrozole is an aromatase inhibitor that is used in the
      treatment of estrogen-sensitive tumors such as endometrial carcinoma, however,
      its therapeutic effect is still to be further improved. It is reported that
      curcumin has antitumor capability and can enhance the sensitivity of tumor cells
      to anticancer agents. This study was to investigate the inhibitory effect of
      letrozole combination with curcumin on the implanted endometrial tumor growth.
      METHODS: Nude mice were implanted with endometrial carcinoma RL-952 cells. All
      tumor-bearing mice were randomly divided into 5 groups: control(without
      treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur
      [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/
      (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was
      detected in both control and treated groups. The expressions of bcl-2 mRNA and
      bcl-2 protein were detected using RT-PCR and Western blot, respectively. RESULTS:
      Fifty mice were successfully implanted with the endometrial tumor. Treatment with
      letrozole markedly inhibited tumor growth; the inhibitory effect was further
      enhanced by the combination of letrozole and curcumin. The inhibitory rates in
      Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%,
      and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl
      2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the
      control group and the four experimental groups mentioned above were 16.97%,
      32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were
      observed in mice treated with either letrozole or curcumin; however, combination
      of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.
      CONCLUSIONS: Treatment with letrozole or curcumin could inhibit the xenografted
      endometrial tumor growth by inducing apoptosis in tumor cells. Combination of
      letrozole and curcumin further enhanced the inhibitory effect of tumor growth.

PMID- 20038304
TI  - [Clinical analysis of 132 cases of cervical adenosquamous carcinoma and cervical
      adenocarcinoma].
AB  - BACKGROUND AND OBJECTIVE: The incidence of cervical adenosquamous carcinoma is
      relatively low. This study was to analyze the clinicopathologic characteristics
      and prognostic factors of cervical adenosquamous carcinoma. METHODS: Clinical
      data of 44 cervical adenosquamous carcinoma patients and 88 cervical
      adenocarcinoma patients(control), treated from January 2002 to December 2007,
      were analyzed using Chi-square test, Kaplan-Meier method, log-rank test, and Cox
      regression model. RESULTS: The proportion of large tumors (maximal diameter > 4
      cm) was significantly higher in cervical adenosquamous carcinoma group than in
      cervical adenocarcinoma group (47.7% vs. 28.4%, P<0.05); the proportion of poorly
      differentiated tumors was significantly higher in cervical adenosquamous
      carcinoma group than in cervical adenocarcinoma group (56.8% vs. 30.7%, P<0.05).
      Univariate analysis showed that tumor size (P=0.011), FIGO stage (P=0.013), depth
      of stromal invasion (P=0.05) and lymph node metastasis (P=0.017) were correlated
      with prognosis, while multivariate analysis showed that FIGO stage and lymph node
      metastasis had great impact on prognosis. There was no significant difference of
      2-year overall and disease-free survival rates between the two groups (P>0.05).
      CONCLUSIONS: Cervical adenosquamous carcinoma is characterized by large tumor
      size and poor differentiation. FIGO stage and lymph node metastasis are
      significant prognostic factors. There is no difference in prognosis between
      cervical adenosquamous carcinoma and cervical adenocarcinoma.

PMID- 20038305
TI  - [Inhibitory effect of cucurbitacin E on the proliferation of ovarian cancer cells
      and its mechanism].
AB  - BACKGROUND AND OBJECTIVE: There are various biological activities of cucurbitacin
      E (CuE), including antitumor effect, anti-chemical carcino-genesis, liver
      protection, and enhancement of the immunity, and so on. This study was to
      investigate the effect of CuE on proliferation inhibition and apoptosis induction
      of ovarian cancer ES-2 cells, and to explore the mechanism. METHODS: ES-2 cells
      were treated with different concentrations of CuE for 24, 48, and 72 h,
      respectively. Cell proliferation was tested by MTT assay. The morphologic changes
      and apoptosis were observed under inverted microscope and fluorescent microscope.
      Cell cycle distribution was evaluated with flow cytometry. The expression of p
      STAT3 was determined by Western blot. RESULTS: The number of ES-2 significantly
      decreased as the concentration of CuE increased or the time prolonged. Flow
      cytometry analysis showed that the ratio of ES-2 cells treated 1 micromol/L CuE
      for 24 h increased both in S phase [from (10.55+/-0.91)% to ( 16.31 +/- 4.61) % ]
      and in G(2)/M phase [from (18.53+/-1.43)% to (58.34 +/- 5.77)%], while decreased
      in G(1) phase [from (73.13 +/-4.70)% to (23.12 +/- 5.45)%] (P<0.05). The marked
      morphological changes of cell apoptosis were clearly observed in ES-2 cells
      treated with CuE. CuE inhibited the STAT3 phosphorylation in ES-2 cell in a dose-
      dependent manner. CONCLUSION: CuE can inhibit ES-2 proliferation and induce
      apoptosis and cell cycle arrest, which may be related to the decreased expression
      of the intracellular STAT3 phosphorylation.

PMID- 20038306
TI  - [Expressions of osteopontin and B7-H4 in epithelial ovarian neoplasm and their
      significance].
AB  - BACKGROUND AND OBJECTIVE: Epithelial ovarian cancer involves a number of factors.
      Recent studies have shown that osteopontin (OPN) is related to the occurrence and
      development of a variety of tumors, but few studies are on ovarian cancer. B7-H4
      is a newly identified tumor marker in ovarian cancer. This study explored the
      expression of OPN and B7-H4 and their clinical significance in epithelial ovarian
      tumors. METHODS: The expression of OPN and B7-H4 in 15 cases of normal ovarian
      tissue, 20 of benign ovarian tumor tissue, 20 of borderline ovarian tumor tissue,
      and 40 of ovarian cancer tissue were detected by immunohistochemistry, and the
      relationship of OPN and B7-H4 expression to clinical and pathologic features of
      ovarian cancer was analyzed. RESULTS: The expression of OPN and B7-H4 were
      significantly higher in ovarian cancer than in borderline and benign tumors
      (P<0.05). The positive rates of OPN and B7-H4 were significantly higher in poorly
      differentiated ovarian cancer than in medium and highly differentiated ovarian
      cancer (P<0.05), and the levels of expression were significantly lower in tissue
      at stages I and III of ovarian cancer than in stages III and IV (P<0.05). The
      positive rate of OPN associated with a higher rate of lymph node metastasis
      (P<0.05), but did not relate to age and histologic type. The positive rate of B7
      H4 were significantly higher in ovarian serous carcinoma than in the mucinous
      carcinoma (P<0.05), but did not relate to age and lymph node metastasis.
      CONCLUSION: The expression of OPN and B7-H4 increased in epithelial ovarian
      cancer, which could be referenced in the diagnosis of ovarian malignant tumors.

PMID- 20038307
TI  - [Solitary spleen metastasis of endometrial carcinoma: a case report].

PMID- 20038309
TI  - [Effect of 5-Aza-CdR on expression and methylation of E-cadherin gene in human
      colon carcinoma cells].
AB  - BACKGROUND AND OBJECTIVE: Colon cancer is one of the most common malignant
      tumors, and its pathogenesis is not fully understood. Transcriptional silencing
      by DNA methylation is believed to be an important mechanism of carcinogenesis. E
      cadherin can suppress tumor cell invasion and metastasis, and is considered as an
      invasion/metastasis suppressor gene. Inactivation of E-cadherin gene often occurs
      in colon carcinoma. This study was to investigate the correlation between E
      cadherin gene expression and the methylation status of E-cadherin 5' CpG islands
      in human colon carcinoma cell line HT-29, and to explore the mechanism of
      carcinogenesis of colon cancer. METHODS: Immunocytochemical dicho-step method and
      reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the
      expression of E-cadherin protein and mRNA in HT-29 cells after 5-Aza-CdR
      treatment; methylation specific PCR was used to analyze the methylation status at
      promoter of E-cadherin gene. RESULTS: The expression of E-cadherin gene could be
      restored by 5-Aza-CdR treatment, immunocytochemical staining showed the positive
      expression ratio of E-cadherin increased from (21+/-7)% (1 micromol/L) to (39+/
      13)% (5 micromol/L); E-cadherin genes were methylated and not expressed in HT-29
      cells in the colon carcinoma. CONCLUSIONS: E-cadherin methylation plays an
      important role in the carcinogenesis of colon carcinoma cells and can re-express
      after the treatment with 5-Aza-CdR.

PMID- 20038308
TI  - [Effect of nitric oxide derived from endothelial nitric oxide synthase on tumor
      angiogenesis].
AB  - BACKGROUND AND OBJECTIVE: Studies have shown that nitric oxide (NO) derived from
      endothelial nitric oxide synthase (eNOS) is expressed widely in tumor tissues and
      regulates tumor angiogenesis. However, the results are controversial. This study
      was to investigate the effect of NO on tumor angiogenesis and its mechanism.
      METHODS: C57BL/6 mice inoculated with Lewis lung cancer cells were randomly
      divided into three groups. Mice in the NO group were inoculated with lung cancer
      cells transfected with eNOS gene, mice in the L-NAME group with L-NAME, an eNOS
      antagonist, and mice in the control group with normal saline. Plasma
      concentration of NO and the number of endothelial progenitor cells (EPCs) in
      peripheral blood were detected . Tumor vessel density, CD133+ cells, and the
      expression of VEGF-VEGFR in tumor tissues were also measured. RESULTS: Four weeks
      after inoculation of Lewis cells, tumor volume was significantly larger in
      control group [ (3022 +/- 401) mm(3)] than in the L-NAME group [ (1204 +/-97) )
      mm(3)] and in the eNOS group [(1824 +/- 239) mm(3)] (P<0.01). eNOS protein and NO
      production increased significantly in Lewis lung cancer cells transfected with
      eNOS gene. But the number of CD133-positive cells and vessel density in tumors
      were significantly lower in the eNOS group than in the control group [(48+/-19) /
      HPF vs. ( 103 +/- 27)/ HPF, (19+/- 7) HPF vs. (31 +/- 9) HPF, P<0.05]. The number
      of EPCs in peripheral blood was not statistically different between each group.
      The levels of NO in blood and tumor tissue significantly decreased after the
      treatment of L-NAME, while the tumor vessel density reduced to 12+/- 5/ HPF
      (P<0.01, vs. the control group; P<0.05, vs the eNOS transfected group). The
      number of EPCs in blood and that of CD133-positive cells in tumor tissue were
      significantly smaller in the L-NAME group than in the control group (P<0.05).
      CONCLUSION: No derived from eNOS inhibits angiogenesis and tumor growth, which
      may be due to its suppression on either the mobilization or homing of EPCs via
      VEGF binding to VEGFR.

PMID- 20038310
TI  - [Effect of short-hairpin RNA expression vector-mediated osteopontin RNA
      interference on proliferation and invasion of prostate cancer PC-3 cells].
AB  - BACKGROUND AND OBJECTIVE: Studies showed that osteopontin (OPN) regulates cell
      migration and invasion in a variety of cancers, which associates with the
      activities of matrix metalloproteinase (MMP)-2 and MMP-9. This study was to
      investigate the role of OPN in the proliferation and invasion of human prostate
      cancer PC-3 cells and the possible functions of IgammaB kinase (IKK) in nuclear
      factor kappa B (NF-kappaB)-mediated signaling pathways. METHODS: OPN short
      hairpin RNA (shRNA) recombinant plasmids were transfected into PC-3 cells and
      different concentrations of IKK inhibitors were used to inhibit the activities of
      IKKalpha and IKKbeta. The mRNA and protein expression levers of OPN, MMP-2, and
      MMP-9 were detected by real-time polymerase chain reaction (PCR) and Western
      blot. Cell cycle was detected by flow cytometry, cell proliferation by MTT assay,
      and cell invasion by Transwell chamber assay. RESULTS: Compared with untreated
      cells, the protein levers of OPN, MMP-2, and MMP-9 in OPN shRNA-transfected PC-3
      cells were reduced by 55.22%, 51.71%, and 28.35%, respectively, and the ability
      of cell migration and invasion were decreased by 45.48% and 51.96%, respectively
      (P<0.05). Moreover, the inhibition of IKKbeta inhibited the expressions of MMP-2
      and MMP-9. CONCLUSION: A shRNA expression vector-mediated OPN gene silencing can
      inhibit the malignant biological behaviors of PC-3 cells. IKKbeta may play a
      crucial role in the OPN-induced activation of MMP-2 and MMP-9 via NF-kappaB
      mediated IkappaB/IKKbeta pathways.

PMID- 20038311
TI  - [Comparative proteomic approach in differentiating multicentric occurrence and
      intrahepatic metastasis in multinodular hepatocellular carcinomas].
AB  - BACKGROUND AND OBJECTIVE: Multinodular hepatocellular carcinoma(HCC) might
      originate from multicentric occurrence (MO) or intrahepatic metastasis(IM). This
      study was to find out proteins which play important roles in clonal origin of
      multinodular hepatocellular carcinoma bt screening the differentially expressed
      proteins between the MO and IM tissues using comparative proteomic analysis.
      METHODS: Total protein extracted was separated by two-dimensional gel
      electrophoresis. Comparative analyses of the 2-DE protein patterns between the
      two groups were carried out using computerized imaging techniques. Proteins
      exhibiting significant alternations were subsequently isolated and identified by
      mass spectrometry. RESULTS: A total 1025+/-52 and 900+/-98 spots were detected in
      the protein profile in IM and MO, respectively. Twenty-five protein spots were
      statistically different at expression levels between the two groups. Twenty of
      them were identified by MALDI-TOF-MS and bioinformatics. CONCLUSIONS: The protein
      profile of MO HCC tissues is different from that in IM HCC tissues. The twenty
      differentially expressed proteins might play a key role in the carcinogenesis and
      progression of multinodular HCC. These newly identified proteins might be
      potential and valuable biomarkers for identifying the multinodular HCC of clonal
      origin.

PMID- 20038312
TI  - [Expression of c-Cbl, Cbl-b, and epidermal growth factor receptor in gastric
      carcinoma and their clinical significance].
AB  - BACKGROUND AND OBJECTIVE: c-Cbl and Cbl-b are two ubiquitous members of the
      Casitas B-lineage lymphoma (Cbl) family, which play important roles in the
      downregulation of epidermal growth factor receptor (EGFR) by acting as E3
      ubiquitin ligases and multiadaptor proteins. This study investigated the
      expression of c-Cbl, Cbl-b, and EGFR in gastric carcinoma and its clinical
      significance. METHODS: The expressions of c-Cbl, Cbl-b, and EGFR were detected by
      immunohistochemistry using tissue microarrays consisting of 124 specimens of
      gastric carcinoma and 16 specimens of normal gastric mucosa. The relationship
      between the expressions of c-Cbl, Cbl-b, and EGFR and clinicopathologic factors
      of gastric carcinoma were analyzed statistically. RESULTS: The positive rates of
      c-Cbl, Cbl-b, and EGFR were higher in the gastric carcinoma group than in the
      normal group (71.0% vs. 18.0%, P<0.01; 82.3% vs. 25.0%, P<0.01; 56.5% vs. 12.5%,
      P<0.01, respectively). The expression of c-Cbl was positively correlated with
      depth of invasion (r=0.219, P=0.015), and TNM staging (r=0.266, P=0.003). The
      expression of Cbl-b was positively correlated with lymph node metastasis
      (r=0.190, P<0.034) and TNM staging (r=0.298, P<0.001). The expression of EGFR was
      positively correlated with depth of invasion (r=0.286, P<0.001) and TNM staging
      (r=0.362, P=0.000). The expression of both c-Cbl and Cbl-b was positively
      correlated with EGFR (r=0.241, P=0.007; r=0.183, P=0.042, respectively).
      Synchronous strong-positive expressions of c-Cbl, Cbl-b, and EGFR were observed
      in 27 specimens of gastric carcinoma, most of which were at advanced stage.
      CONCLUSIONS: Overexpressions of c-Cbl, Cbl-b, and EGFR are closely related to the
      invasion and progression of gastric carcinoma. c-Cbl and Cbl-b may serve as novel
      molecular markers for gastric carcinoma.

PMID- 20038313
TI  - [In vitro study of human multiple myeloma cell transfected with soluble vascular
      endothelial growth factor receptor-1 gene].
AB  - BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is the most
      important angiogenic factor of multiple myeloma (MM). This study was to
      investigate the effect of transfection of human soluble vascular endothelial
      growth factor receptor-1 (sFlt-1) gene on the proliferation of human MM cell line
      RPMI8226. METHODS: The recombinant plasmid pcDNA3-sFlt-1 was constructed and
      transfected into RPMI8226 cells. The expression of sFlt-1 was identified by
      reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. The effects
      of sFlt-1 protein on the proliferation and VEGF expression of RPMI8226 cells were
      investigated by MTT assay and ELISA, respectively. RESULTS: The recombinant
      plasmid pcDNA3-sFlt-1 was successfully transfected into RPMI8226 cells. sFlt-1
      protein expression was identified by ELISA, which inhibited the proliferation of
      RPMI8226 cells and reduced VEGF concentration in the culture supernatant.
      CONCLUSION: RPMI8226 cells can express sFlt-1 protein with high biological
      activity when transfected with the sFlt-1 gene, which inhibits the proliferation
      of RPMI8226 cells.

PMID- 20038314
TI  - [Relationship between HER2/neu gene amplification and protein expression and
      prognosis in patients with advanced gastric carcinoma].
AB  - BACKGROUND AND OBJECTIVE: There is a mounting evidence of the role of HER2
      overexpression inpatients with gastric cancer, and it has been solidly correlated
      with poor outcomes and more aggressive diseases. This study was to investigate
      the relationship between the expression of HER2/neu and the clinical
      characteristics of advanced gastric carcinomas, including survival. METHODS: The
      clinical data of 83 patients admitted in Cancer Hospital, Chinese Academy of
      Science, from 2006 to 2008 were reviewed. The HER2/neu status in 83 advanced
      gastric carcinomas was evaluated using immunohistochemistry (IHC) and
      fluorescence in situ hybridization (FISH). The survival rate was calculated by
      Kaplan-Meier method and the log-rank test using SPSS13.0 software. RESULTS: The
      median age of the patients was 60 years and the male-to-female ratio was 2.95:1.
      HER2/neu overexpression (2+ and 3+) and amplification were found in 25 (30.1%)
      and 29 (34.9%) advanced gastric carcinomas, respectively. HER2/neu
      amplification/overexpression was associated with worse survival in patients with
      advanced gastric carcinoma. The median survival of the patients without HER2/neu
      amplification was 12.6 months and that of those with HER2 amplification was 5.5
      months. CONCLUSIONS: HER2/neu status may be a clinical predictor of prognosis in
      advanced gastric cancer patients.

PMID- 20038315
TI  - [Correlation of epidermal growth factor receptor mutations and HER2/3 protein
      expression with clinical outcome in advanced non-small cell lung cancer patients
      treated with gefitinib].
AB  - BACKGROUND AND OBJECTIVE: The effect of gefitinib on advanced non-small cell lung
      cancer (NSCLC) was various. How to choose the sensitive patients and improve the
      effect was difficulty in clinic. This study was to assess the correlation of
      epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression
      with the effect of gefitinib on Chinese patients with advanced NSCLC. METHODS:
      From May 2002 to February 2005, a total of 106 Chinese NSCLC patients who had
      failed at least one chemotherapy regimen were treated with gefitinib 250 mg once
      a day. The mutations in the exons 18-24 of EGFR gene were detected in the tumor
      tissues from 106 patients before the treatment of gefitinib, and HER2/3
      expression in 84 tumor samples were detected by immunohistochemistry. RESULTS:
      Mutation was identified in 32 (30.2%) tumor tissues. Overall remission rate was
      significantly higher in the HER2 high expression patients than in the HER2 low
      expression patients (36.8% vs 17.4%, P=0.044). HER2 and HER3 expression levels
      were not associated with time to progression (TTP) and overall survival (OS). The
      patients with HER2/3 single high expression had relatively longer TTP and OS than
      those with HER2/3 single low expression (6.1 vs 9.1 months, P=0.725; 6.1 vs 9.0
      months, P=0.862), while those with concomitant HER2/3 high expression had
      significant longer TTP and OS. EGFR-mutated patients with HER2 expression or high
      HER2 and HER3 expressions were more sensitive to gefitinib. CONCLUSION: EGFR
      mutations combined with HER2/3 expressions is a significant predictor for
      gefitinib efficacy on Chinese patients with advanced NSCLC.

PMID- 20038316
TI  - [Clinical features of 337 patients with recurrent nasopharyngeal carcinoma].
AB  - BACKGROUND AND OBJECTIVE: At present, although appropriate radiotherapy and
      combined treatments are widely used for the patients with primary nasopharyngeal
      carcinoma (NPC), local or regional recurrence rates are still high. According to
      clinical performance, pathology, and diagnostic imaging of the patients with the
      first recurrence of NPC, this study analyzed the clinical features of recurrent
      NPC to provide a reference for tracking the rules of recurrence after the
      treatment of patients with NPC. METHODS: Clinical data of 337 patients diagnosed
      with recurrent NPC for the first time were collected. The diagnoses were based on
      pathology and/or imaging and the patients were treated at the Sun Yat-sen
      University Cancer Center between January 1999 and December 2004. Data used for
      statistical analysis included clinical performance during the patient visit, the
      extension of the invasion as shown on imaging, pathologic features, Epstein-Barr
      virus (EBV) serology, restaging, etc. RESULTS: Patients were staged according to
      the system developed by the International Union Against Cancer (UICC) and the
      American Joint Committee on Cancer (AJCC) in 2002. Patients with diseases at
      stages I/II accounted for 25.2%, while those with stage III/IV accounted for
      74.8%. The median interval of relapse was 25 months. Patients had local
      recurrence (69.4%), regional recurrence (4.5%), or both (26.1%). Epistaxis and
      headache were the most common symptoms. Abduct dysfunction and facial numbness
      induced by cranial nerve damage were the most common signs. The probability of
      invasion of structures adjacent to the nasopharynx, such as the oropharynx, the
      prestyloid space, and the carotid sheath area, was low in patients with recurrent
      NPC. By contrast, the probability of invasion of structures far from the
      nasopharynx, such as the base of the skull, the paranasal sinuses, cranial
      nerves, the cavernous sinus, the brain, the pterygopalatine fossa, the
      infratemporal fossa, the orbital apex, and the soft palate, was higher in
      recurrent NPC. CONCLUSIONS: The most common interval of relapse is about 2 years.
      The relapsed disease is usually more widespread and located deeper. Most
      recurrent NPC is advanced disease.

PMID- 20038317
TI  - [Influence of level-Ib lymphadenopathy on the prognosis of nasopharyngeal
      carcinoma].
AB  - BACKGROUND AND OBJECTIVE: The level-Ib lymph node metastasis is rare in
      nasopharyngeal carcinoma (NPC). When and how this level should be irradiated with
      precise radiotherapy remains controversial. This study evaluated the prevalence
      and prognostic significance of level-Ib lymphadenopathy on the prognosis of NPC
      patients. METHODS: From January 1990 and December 1999, 933 newly diagnosed
      patients with NPC treated at Sun Yat-sen University Cancer Center were randomly
      selected, examined with computed tomography (CT) imagining for evidence of level
      Ib lymphadenopathy before treatment. All patients received radical radiotherapy
      with or without chemotherapy. The relationship between level-Ib lymphadenopathy
      and post-treatment outcomes including overall survival (OS), locoregional
      recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were
      analyzed using Kaplan-Meier methods. The Cox proportional hazards regression
      model was used to adjust for other prognostic factors. RESULTS: Of the 933
      patients, 55 (5.9%) were found to have level-Ib lymphadenopathy, which was
      associated with carotid sheath involvement, oropharynx involvement and levels,
      and lateral cervical lymph node involvement. In the subgroup with carotid sheath
      involvement, with multivariate analysis accounting for all previously known
      prognostic factors, level-Ib lymphadenopathy was still associated with a risk of
      decreased OS (RR, 2.124; P<0.001), DMFS (RR, 2.168; P<0.001), and LRFS (RR,
      1.989; P=0.001). CONCLUSION: Level-Ib lymphadenopathy in the patients with
      carotid sheath involvement is an independent prognostic factor.

PMID- 20038318
TI  - [Trend analysis for clinical characteristics and prognosis of adenocarcinoma of
      cardia].
AB  - BACKGROUND AND OBJECTIVE: The incidence of adenocarcinoma of the cardia has
      recently increased. This study compared the clinicopathology and prognosis of
      patients with gastric cardia adenocarcinoma in different periods between 1984 and
      2003. METHODS: A total of 589 patients with pathologically confirmed gastric
      cardia adenocarcinoma hospitalized in Sun Yat-sen University Cancer Center
      between 1984 and 2003 were divided into 5-year groups. Retrospective analysis of
      clinical and prognostic characteristics between the different 5-year groups was
      conducted. RESULTS: The number of hospitalized patients increased by 134.5%, with
      an annual increase of 4.6%. Median age was 60 years, with an increase of 5 years.
      Patients aged between 55 years and 64 years decreased, while patients aged > or =
      65 years increased. The male-to-female ratio was 2.88:1, with no significant
      change. The rates of patients with the stage-I and -II disease changed
      insignificantly, while patients with stage-III disease increased, and patients
      with stage-I disease decreased. The 5-year survival rate of all the patients was
      28.5%, which increased from 20.9% between 1984 and 1993 to 35.5% between 1994 to
      2003. CONCLUSIONS: During the past 20 years, associated with the upward-trending
      incidence of gastric cardia adenocarcinoma, the admission rate at our hospital of
      patients with the tumor increased. The median age of the patients also increased.
      The ratio of men to women had no significant change. The proportion of patients
      with late-stage disease decreased and prognosis has improved.

PMID- 20038319
TI  - [Experience of the treatment for clinical Stage-1 seminoma over a period of 10
      years].
AB  - BACKGROUND AND OBJECTIVE: Patients with clinical stage I seminoma accounts for
      70%-80% of patients with this disease. This study was to analyze the relationship
      between different therapeutic methods and the prognosis of this disease. METHODS:
      The data of all patients with clinical Stage I seminoma treated by multi
      disciplinary approach from 1999 to 2008 in Sun Yat-sen University Cancer Center
      were analyzed. The patients were divided into 3 groups based on the treatment
      they received after orchiectomy: 30 patients treated with chemotherapy, 8 with
      radiotherapy, and 20 under surveillance. The prognosis of different treatment
      groups was evaluated. RESULTS: Among the 58 patients with stage I seminoma, 57
      were followed up successfully. The median follow-up time was 50 months (range, 8
      115 months). No relapse or metastasis was seen in the chemotherapy group. One
      patient relapsed in the radiotherapy group. Four patients had metastasis of
      retroperitoneal lymph node in the surveillance group. The disease-free survival
      was higher in the chemotherapy group than that in the surveillance group
      (P=0.005). There was no significant difference in the relapse-free survival
      between the surveillance group and the radiotherapy group (P=0.364). CONCLUSIONS:
      Chemotherapy is a safe and effective treatment for patients with Stage-1 seminoma
      after radical orchidectomy.

PMID- 20038320
TI  - [Clinical features of hypersensitivity reactions to oxaliplatin among Chinese
      colorectal cancer patients].
AB  - BACKGROUND AND OBJECTIVE: Oxaliplatin is one of the effective drugs for the
      treatment of advanced colorectal cancer (CRC). Oxaliplatin-induced allergic
      reactions in European and American patients have been reported, but in China
      there are only a few case reports. This study investigated the incidence rate and
      characteristics of oxaliplatin-induced allergic reactions in Chinese patients
      with CRC. METHODS: Clinical data of 109 patients with advanced CRC receiving
      oxaliplatin plus capecitabine (the XELOX regimen) as first-line therapy were
      collected and analyzed retrospectively. RESULTS: Of 109 patients, 13 (11.9%)
      patients had hypersensitivity. In 546 cycles, 23 (4.2%) cycles involved
      hypersensitivity. Grade-I,-II, and -III reactions were seen in 13 cycles, 8
      cycles, and 2 cycles, respectively, and no grade-IV reaction was observed.
      Allergic reactions usually occurred at the median time during the fifth cycle
      (range, the 1st-8th cycle) of oxaliplatin-containing therapy, and the cumulative
      oxaliplatin dose was 1200 mg (range, 400-1600 mg). Symptoms associated with
      anaphylaxis appeared 5-360 min (median, 180 min) after oxaliplatin infusion, and
      were relieved after withdrawing the oxaliplatin infusion and treating with
      antiallergic drugs. A total of 8 patients continued to receive oxaliplatin
      therapy after prophylactic administration of antiallergic drugs, such as
      steroids, and 4 patients did not report persistent allergic reactions. Compared
      with men, oxaliplatin-induced allergic reactions were more commonly seen in women
      patients (P<0.05), while age, body surface area, performance status, tumor
      location, and pathologic type showed no significant difference. CONCLUSION:
      Oxaliplatin-induced allergic reactions occurred in Chinese patients with CRC, and
      the incidence rate, occurrence time, degree of severity, and clinical outcome
      were consistent with literature published abroad.

PMID- 20038321
TI  - [Prophylactic irradiation of cervical lymph nodes for Stage-N0 nasopharyngeal
      carcinoma].
AB  - BACKGROUND AND OBJECTIVE: It is controversial for the irradiation level and dose
      of the regional prevention for naspharyngeal cancer (NPC) with one or both
      cervical lymph node-negative neck. The study was to analyze the proophylactic
      irradiation of cervical lymph nodes for Stage -N0 NPC patients. METHODS: From
      January 2002 and December 2004, 205 NPC patients with negative lymphadenopathy
      diagnosed by imaging, were retrospectively analyzed. Before treatment, each
      patient underwent CT or MRI. Facial-cervical portals and 6-8 MV photons were used
      in radiotherapy. Doses applied were 60-80 Gy to the nasopharynx and 46-64 Gy to
      the neck without lymphadenopathy. Consecutive radiotherapy was performed
      employing conventional fractionation of 2 Gy/fraction, once a day, for a total of
      five fractions per week. Chemotherapy was administered to 60 patients. Median
      follow-up was 44 months. The survival function was calculated according to the
      Kaplan-Meier method. A log-rank test was used to compare the differences in
      survival. The Cox proportional hazards model was used for multivariate analysis.
      A total of 205 patients with stage-N0 NPC were divided into an upper-neck
      irradiation group and an entire-neck group. RESULTS: The 3-year overall survival
      rate (OS) was 92.9% and the 3-year disease-free survival rate (DFS) was 91.9%. A
      total of 88 patients received irradiation to the upper neck and 117 to the entire
      neck. The rate of regional failure for the upper-neck group and the entire-neck
      group were 2.27% and 0%, respectively (P>0.05). The rates of regional failure in
      patients with T1-, T2-, T3- and T4-stage disease were 0, 3.08%, 0, and 0,
      respectively (P>0.05). The rates of regional failure in the patients both without
      and with local failure were 1.03% and 0, respectively (P>0.05). The 1-and 3-year
      OS for the upper-neck group were 97.7% and 94.2%, and the 1- and 3-year OS for
      the entire-neck group were 97.4% and 91.9% (P=0.950). The 1- and 3-year DFS for
      the upper-neck group were 96.6% and 92.9%, and the 1- and 3-year DFS for the
      entire-neck group were 95.6% and 90.9% (P= 0.730). In multivariate analysis, sex
      (P=0.039) and T stage (P=0.004) were independent prognosis factors for patients
      with stage-N0 NPC. CONCLUSIONS: Prophylactic irradiation to the upper neck does
      not influence regional failure or long-term survival in the patients with stage
      N0 NPC. Radiotherapy to the upper neck (levels II, III, VA) is recommended for
      the patients with stage-N0 NPC. Involvement of the parapharyngeal space, T stage,
      and the rates of local failure do not influence regional failure in these
      patients. Sex and T stage were independent prognosis factors of stage-N0 NPC
      patients.

PMID- 20038322
TI  - [OCT4 expression in hepatocellular carcinoma and its clinical significance].
AB  - BACKGROUND AND OBJECTIVE: Recently, many studies have focused on stem cells in
      hepatocellular carcinoma (HCC) and found some stem cell markers in HCC, which are
      associated with the prognosis. OCT4, as a member of the POU transcription factor
      family, is a key factor to maintain self-renewal and pluripotency of embryonic
      stem cells (ESCs). This study was to explore the expression of the ESCs marker
      OCT4A in HCC, and its correlations with clinicopathologic features and prognosis
      of HCC. METHODS: OCT4A mRNA expression was detected in five liver cancer cell
      lines (SMMC-7721, BEL-7402, Hep-G2, MHCC97-L, and MHCC97-H), one immortalized
      liver cell line L-O2, tumor tissues with matched non-neoplastic liver tissues in
      107 HCC patients, and normal liver tissues of 20 cases using semi-quantitative
      reverse transcription-polymerase chain reaction (RT-PCR). The correlations
      between OCT4A mRNA and clinicopathologic features and prognosis of HCC were
      analyzed. RESULTS: OCT4A mRNA was detected in SMMC-7721, BEL-7402, Hep-G2, MHCC
      97L, and MHCC-97H cells, but not in L-O2 cells. The positive rate of OCT4A mRNA
      expression was significantly higher in the HCC tissues than in the non-neoplastic
      liver tissues (72.0% vs. 30.8%, P<0.001). No OCT4A mRNA expression was found in
      the normal liver tissues. OCT4A mRNA expression was correlated with the tumor
      size, vascular invasion, and TNM stage (P<0.05). Kaplan-Meier survival curves
      showed that patients with positive expression of OCT4A mRNA had lower overall
      survival and disease-free survival rates. CONCLUSIONS: OCT4A mRNA, which is
      highly expressed in a subset of liver cancer cell lines and HCC tissues, may be
      involved in the carcinogenesis of HCC. OCT4A mRNA may be a valuable biomarker for
      assessing the prognosis of HCC.

PMID- 20038323
TI  - [Application of a narcotrend-assisted anesthesia in-depth monitor in the
      microwave coagulation for liver cancer during total intravenous anesthesia with
      propofol and fentanyl].
AB  - BACKGROUND AND OBJECTIVE: CT-guided microwave coagulation is a minimally invasive
      surgery for patients with liver cancer. Total intravenous anesthesia with
      propofol and fentanyl is commonly used. The depth of anesthesia during microwave
      coagulation for liver cancer is still monitored by clinical signs. There are few
      subjective and effective indicators. This study explored the application of
      Narcotrend-assisted "depth of anesthesia" monitoring on microwave coagulation for
      patients with liver cancer during total intravenous anesthesia with propofol and
      fentanyl. METHODS: Forty liver cancer patients underwent CT-guided microwave
      coagulation were randomly assigned to receive Narcotrend index monitoring or
      standard clinical monitoring for depth of anesthesia with 20 patients in each
      group. All patients received total intravenous anesthesia with propofol and
      fentanyl. The depth of anesthesia for patients in the Narcotrend group was
      measured according to a Narcotrend index, which was maintained between D2 and E0.
      The depth of anesthesia for those in the standard clinical practice group was
      measured according to heart rate, mean arterial pressure, and patient movement.
      Changes of hemodynamics, the duration of the emergence from anesthesia, and the
      recovery of orientation were recorded. The doses of propofol and fentanyl,
      postoperative visual analogue scores (VAS), and the incidence of postoperative
      nausea and vomiting were also recorded. RESULTS: There was no significant
      alteration in heart rate or mean arterial pressure between the two groups.
      Compared with other anesthetic stages, both heart rate and mean arterial pressure
      decreased during the induction of the anesthesia in the two groups(P<0.05). The
      doses of propofol were higher in the standard clinical practice group than in the
      Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P<0.01]. The duration of
      emergence and orientation were longer in the standard clinical practice group
      than in the Narcotrend group [(9.5+/-2.9) min vs. (4.9+/-2.2) min, P<0.01;
      (12.2+/-3.5) min vs. (6.6+/-3.2) min, P<0.01, respectively]. There was no
      difference in the dosage of fentanyl, VAS, or the incidence of postoperative
      nausea or vomiting between the two groups (P>0.05). CONCLUSION: For patients with
      liver cancer, monitoring the depth of anesthesia with Narcotrend on microwave
      coagulation can contribute to lower dosage of propofol and shorten duration of
      recovery during total intravenous anesthesia with propofol and fentanyl.

PMID- 20038324
TI  - [Prosthesis replacement of the proximal humerus after the resection of bone
      tumors].
AB  - BACKGROUND AND OBJECTIVE: After chemotherapy was used to treat patients with
      malignant bone tumors in 1970s, amputation, which was the typical intervention in
      the 1980s, has been substituted with limb-sparing surgery. This article reported
      the surgical indications, operative methods, operative effects, and complications
      of prosthetic replacement of the proximal humerus after the resection of bone
      tumors. METHODS: From April 2004 and December 2008, prosthetic replacement was
      performed in 18 patients with proximal humerus tumors, including 7 patients with
      osteosarcoma, 5 patients with chondrosarcoma, 3 patients with giant cell tumor
      (GCT) of the bone, 1 patient with GCT of the bone combined with an aneurysmal
      bone cyst, and 1 patient with metastatic bone tumors. Using the Enneking staging
      system, 7 osteosarcomas and 3 chondrosarcomas were at stage Ib, and 3 GCTs and 2
      chondrosarcomas were at stage Ib. The patient with metastatic bone tumors
      reported severe pain. RESULTS: The follow-up ranged 5-61 months (mean, 29 months)
      and showed that 1 patient with osteosarcoma died 19 months after surgery. Local
      recurrence presented in 1 patient with GCT, 1 patient had inner infection in the
      area of surgery, and 2 patients had shoulder subluxation after the operation.
      There was no prosthetic loosening in any patient. The abduction angle of the
      shoulder was 8 degrees-35 degrees, and circumgyrate angle was 18 degrees-25
      degrees, with flexion 35 degrees-90 degrees and extension 25 degrees-42 degrees.
      According to the functional score developed by the International Society of Limb
      Salvage, scores ranged between 18 and 29 points, with an average of 24 points.
      CONCLUSIONS: The prosthesis replacement for the patients with bone tumors in the
      proximal humerus is an appropriate procedure with satisfactory therapeutic
      outcomes; however, many complications should be noted and long-term therapeutic
      effect needs further investigations.

PMID- 20038325
TI  - [Application and advancement of magnetic iron-oxide nanoparticles in tumor
      targeted therapy].
AB  - Recently, nanometer-sized magnetic particles have been intensively concerned and
      investigated due to their particularly large surface-to-volume ratio, quantum
      size effect, magnetic character as well as their potential application in the
      area of bioscience and medicine. The most promising nanoparticles are magnetic
      iron oxide nanoparticles with appropriate surface modification, which have been
      widely used experimentally for numerous in vivo applications such as magnetic
      resonance imaging contrast enhancement, tissue repair, immunoassay,
      detoxification of biological fluids, drug delivery, hyperthermia and cell
      separation. To focus on one of the most important and fascinating subjects in
      nanobiotechnology, this review describes the current situation and development of
      magnetic iron oxide nanoparticles and their applications in drug delivery and
      hyperthermia in tumor-targeted therapy. The possible perspectives and some
      challenges to further development of these nanoparticles are also analyzed and
      discussed.

PMID- 20038326
TI  - [Results of 3 years of continuous entecavir treatment in nucleos(t)ide-naive
      chronic hepatitis B patients].
AB  - OBJECTIVE: To evaluate the virological, serological and biochemical outcomes of 3
      years of entecavir (ETV) treatment in nucleoside-naive chronic hepatitis B
      patients. METHODS: This study was divided into two stages: Patients receiving
      either ETV 0.5 mg/d (n = 258) or lamivudine (LAM) 100 mg/d (n = 261) entered the
      initial 96-week randomized, double blind, controlled efficacy study. Patients not
      achieving a consolidated response (HBV DNA less than 0.7 MEq/ml, ALT less than
      1.25 times*ULN, and if HBeAg-positive at baseline, loss of HBeAg for >or= 24
      weeks), or those experienced viral breakthrough or relapse, entered a 48-week
      entecavir rollover study. RESULTS: 96 weeks after the treatment, 79% of ETV
      treated and 46% of LAM treated patients had HBV DNA less than 300 copies/ml (P <
      0.0001), 96% of ETV treated and 92% of LAM treated patients had normalized ALT (P
      = 0.06). 21% of ETV treated and 23% of LAM treated patients achieved HBeAg
      seroconversion. Among the 160 patients received continuous ETV for 144 weeks, 89%
      had undetectable serum HBV DNA, 86% showed ALT normalization, and 27% achieved
      HBeAg seroconversion. ETV resistance was rare: only 3 patients showed ETV
      resistance 96 weeks after the treatment, and additional 2 patients developed ETV
      resistance during the following 48 weeks, genotyping indicated the ETV resistance
      was caused by gene mutation. Adverse event rates in ETV-treated patients were
      similar to those in LAM-treated patients, but fewer ALT flares were observed in
      ETV-treated patients. CONCLUSIONS: This study demonstrates that ETV treatment
      results in long-term HBV suppression and ALT normalization in Chinese CHB
      patients, and is associated with low rate of drug resistance.

PMID- 20038327
TI  - [The spontaneous YMDD mutation rate in chronic hepatitis B patients].
AB  - OBJECTIVE: To investigate the spontaneous YMDD mutation rate. METHODS: Serum
      samples collected from 196 untreated chronic HBV patients were detected by primer
      specific real-time PCR. RESULTS: Among 196 patients, spontaneous YMDD variants
      were detected in 21 subjects (20 YVDD mutants and 1 YIDD mutant). YMDD variants
      account for more than 50%, 25% to 50%, 9% to 25% of total virus load in 1, 5 and
      15 patients, respectively. Gender, age, HBeAg status, serum viral load, the state
      of disease and duration of infection were not associated with spontaneous YMDD
      mutation. Genotype B had higher spontaneous YMDD rate than genotype C (20.00% vs
      7.38%, x(2) = 6.28, P < 0.05). CONCLUSION: Spontaneous YMDD variants exist in
      chronic hepatitis B patients, Genotype B is associated with higher spontaneous
      YMDD rate.

PMID- 20038328
TI  - [Establishment of reference sequences of hepatitis B virus genotype B and C in
      China].
AB  - OBJECTIVE: To establish the reference sequences of genotype B and C of hepatitis
      B virus in China. METHODS: Genome sequences of Hepatitis B virus isolated from
      different area in China were retrieved from GenBank. These genome sequences were
      alignmented and the most common sequences were regarded as reference sequences.
      The amino acid sequences were also alignmented. RESULTS: The homology was 99.32%
      between Bc genome and Ba genome, and it was 95.52% between Bc genome and Bj
      genome. The S gene sequence homology was 99.71% between Bc and Ba, and it was
      98.68% between Bc and Bj. The homology was 98.44% between Cc genome and C genome,
      and it was 93.97% between Cc genome and Caus genome. The S gene sequence homology
      was 99.27% between Cc and C, and it was 95.01% between Cc and Caus. There was
      significant difference at the sites of 1762, 1764, 1858 between genotype B and
      genotype C (P < 0.05). The amino acid sequences were also different between
      genotype B and genotype C. CONCLUSION: Bc and Cc sequences of Hepatitis B virus
      can be regarded as the reference sequences of genotype B and C.

PMID- 20038329
TI  - [A study on seroprevalence of anti-HAV IgG in adults of 4 cities in China].
AB  - OBJECTIVE: To investigate the seroprevalence of anti-HAV IgG in adults of 4
      cities in China. METHODS: Serum samples were collected from 2390 local residents
      aged between 20 to 88 years from Beijing, Shanghai, Wuhan and Guangzhou. The anti
      HAV IgG in sera was detected with a microparticle enzyme immunoassay (MEIA).
      RESULTS: The anti-HAV IgG seroprevalence in female of 30 to 39 years in Beijing
      (64.58%, 62/96) was higher than that in male (45.57% 36/79)) (x(2) = 6.358, P =
      0.012). It increased with age in adults of Beijing and Guangzhou. The rates were
      54.22 % (90/166), 56.00% (98/175) and 67.18% (88/131) for the 20-, 30- and 40-49
      age groups in Beijing (x(2) = 4.76, P = 0.03); and 52.83% (56/106), 52.50%
      (63/120), 82.46% (94/114), 89.80% (88/98) and 96.77% (60/62) for the 20-, 30-, 40
      , 50- and 60-88 age groups in Guangzhou, respectively (x(2) = 72.58, P less than
      0.01). This trend was not found in Shanghai and Wuhan (x2 = 0.96, 2.99; P = 0.33,
      0.08 respectively). The seroprevalence rates of anti-HAV IgG in the 20 to 39 age
      group of Beijing, Shanghai, Guangzhou and Wuhan were 55.13% (188/341), 63.93%
      (429/671), 52.65% (119/226) and 78.37% (308/393), respectively. CONCLUSION: The
      seroprevalence rates of anti-HAV IgG in young adults aged 20 to 39 years of the
      four cities are relatively low, and HAV vaccination should be suggested for the
      susceptible population of this age group in China.

PMID- 20038330
TI  - [Inhibition of hepatitis B virus (HBV) replication using antisense LNA targeting
      to both S and C genes in HBV].
AB  - OBJECTIVE: To investigate the inhibitory effect on HBV replication of antisense
      locked nucleic acid (LNA) targeting to both S and C genes in HBV transgenic mice.
      METHODS: Thirty HBV transgenic mice were randomly divided into five groups (n =
      6): glucose control group were treated with 5% glucose solution, liposome control
      group were treated with liposome alone, S group were treated with LNA targeting
      to S gene, C group were treated with LNA targeting to C gene, and dual-target
      group were treated with LNA targeting to both S and C genes. Antisense LNA was
      injected into mice via the tail vein. Serum HBsAg was quantified by TRFIA. Serum
      HBV DNA was quantified by real-time PCR. The expression of HBV C-mRNA in the
      liver was detected by RT-PCR. The expression of HBsAg and HBcAg in the liver was
      detected by immunohistochemistry. Serum ALB, ALT, BUN and CR were measured using
      an automatic biochemical analyzer. The effects of antisense LNA on mouse organs
      were investigated by HE staining. RESULTS: 5 days after LNA injection, serum
      HBsAg levels in the dual-target group were reduced by 72.8%, and serum HBV DNA
      levels were decreased by 52.9%. These values were significantly higher than those
      in the control groups (all P < 0.05). No significant differences were noted in
      serum ALB, ALT, BUN and CR between the experiment groups and the control groups
      (all P > 0.05). The expression levels of HBsAg and HBcAg in the liver of dual
      target group were significantly lower than those in the control groups. No
      significant histopathological abnormality was found in liver and kidney tissues
      in all groups. CONCLUSION: Antisense LNA targeting to both S and C genes can
      significantly inhibit HBV replication in transgenic mice.

PMID- 20038331
TI  - [The significance of antimitochondrial IgA and IgG in the diagnosis of primary
      biliary cirrhosis].
AB  - OBJECTIVE: To evaluate the sensitivity and the specificity of Anti-M2-3E ELISA
      for the detection of IgG- and IgA-specific isotypes of antimitochondrial antibody
      (AMA), and to investigate the significance of antimitochondrial IgA and IgG in
      the diagnosis of primary biliary cirrhosis (PBC). METHODS: Sera were collected
      from 107 PBC patients, 87 disease controls and 26 healthy controls, and the
      antimitochondrial antibodies (IgG and IgA) were detected using indirect
      immunofluorescence (IFL), Anti-PDC ELISA and Anti-M2-3E ELISA. RESULTS: The AMA
      IgG positive rate in PBC patients was 90.6% detected by Anti-M2-3E ELISA, which
      is significantly higher than that (81.3%) detected by IFL(t = 4.32, P < 0.05) and
      that (72.9%) detected by Anti- PDC ELISA (t = 6.03, P < 0.05). The AMA IgA was
      positive in 59 of the 107 PBC patients, and 99 of the 107 patients were positive
      for AMA IgG or/and IgA. 9 of the 20 IFL-negative patients were positive for AMA
      IgG as indicated by Anti-M2-3E ELISA, 11 of the 20 IFL-negative patients were
      positive for AMA IgG or/and IgA as indicated Anti-M2-3E ELISA. Compared to
      patients negative for IgG AMA, patients positive for IgG AMA had more severe
      histopathology and higher levels of ALP, IgG, and IgM. CONCLUSION: The IgG and
      IgA Anti- M2-3E ELISAs are more sensitive for the AMA detection than IFN and the
      Anti-PDC ELISA. The presence of AMA IgG is the characteristics of severe PBC.

PMID- 20038332
TI  - [The effect of urokinase on hepatic fibrogenesis in rats].
AB  - OBJECTIVE: To investigate the effect of urokinase on hepatic fibrogenesis in
      rats. METHODS: Hepatic fibrosis was induced in rats by complex pathogenic factors
      including subcutaneous injections of carbon tetrachloride, alcohol and
      cholesterol feeding. Animals were randomly divided into 3 groups: normal control
      group, hepatic fibrosis group (complex pathogenic factors for 6 weeks), UK
      prevention group (complex pathogenic factors+UK for 6 weeks). The animals were
      sacrificed at the end of week 6. The expression of alpha-SMA, uPA, PAI-1, TGFb1,
      TIMP-1, collagen type I and type III proteins in hepatic fibrosis tissue was
      detected by immunohistochemistry, the expression of PAI-1 and TGFb1 mRNA in the
      hepatic fibrosis tissue was quantified by real time RT-PCR. The serum levels of
      hyaluronicacid (HA), alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), bilirubin (TBil) and the content of liver hydroxyproline (Hyp) were
      detected using ELISA kits. RESULTS: The serum ALT, AST, TBil, HA and the content
      of liver Hyp were (46.66+/-6.30) U/L, (126.26+/-31.65) U/L, (31.11+/-4.20)
      micromol/L, (109.70+/-18.81) microg/L and (0.98+/-0.09) mg/(g liver),
      respectively, in UK prevention group, which were significantly lower than those
      [(101.57+/-11.97) U/L, (205.89+/-56.26) U/L, (67.75+/-2.75) micromol/L, (184.43+/
      32.36) microg/L and (1.65+/-0.16) mg/(g liver), respectively] in hepatic fibrosis
      group (q = 3.3801-20.0061, P < 0.01). The levels of a-SMA, collagen type I, type
      III, TIMP-1, PAI-1, TGFb1 proteins were (299.27+/-37.36), (210.05+/-27.17),
      (192.94+/-24.48), (213.70+/-32.21), (204.25+/-17.92), (205.97+/-23.81),
      respectively, in UK prevention group, which were significantly lower than those
      [(418.83+/-30.21), (323.77+/-21.53), (302.37+/-31.43), (376.63+/-25.19),
      (313.53+/-26.67) and (327.42+/-36.75), respectively] in hepatic fibrosis group.
      The level of uPA protein was increased, and the expression of PAI-1, TGFb1 mRNA
      in hepatic fibrosis tissue was decreased in UK prevention group. CONCLUSION: In
      the early stage of hepatic fibrogenesis, urokinase can attenuate the progression
      of rat hepatic fibrosis via upregulation of uPA, downregulation of TGFb1, and
      inhibition of HSC activation.

PMID- 20038333
TI  - [Effect of interleukin 10 gene-modified bone marrow-derived liver stem cells
      transplantation on hepatic inflammatory response and liver regeneration in
      hepatic fibrosis rats].
AB  - OBJECTIVE: To explore effect of interleukin 10 (IL-10) gene-modified bone marrow
      derived liver stem cells (BDLSCs) transplantation on hepatic inflammatory
      response and liver regeneration in rats with liver fibrosis. METHODS: 50 female
      Wistar rats were randomly divided into 4 groups: (1) control group: 10 rats were
      subcutaneously injected with olive oil for 8 weeks; (2) fibrosis groups: 16 rats
      were subcutaneously injected with carbon tetrachloride (CCl4) for 8 weeks to
      induce liver fibrosis; (3) BDLSC group: 12 rats were subcutaneously injected with
      CCl4 for 8 weeks, and were transplanted with 2 x 10(5) BDLSC at week 4; (4)
      BDLSC/IL-10 group: 12 rats were subcutaneously injected with CCl4 for 8 weeks,
      and were transplanted with 2 x 10(5) IL-10 gene-modified BDLSC at week 4. IL-10
      and tumor necrosis factor alpha (TNFa) in liver tissues were detected by ELISA.
      HE stained liver tissues were observed under light microscope. The expression of
      hepatocyte growth factor (HGF) was quantified by real-time RT-PCR, and the
      expression of proliferating cell nuclear antigen (PCNA) was determined by
      immunohistochemistry. RESULTS: The ratio of IL-10/TNFa in fibrosis group (0.05+/
      0.01) was lower than that in control group (0.26+/-0.04) (P < 0.01).
      Transplantation of untreated BDLSCs did not improve the ratio (P > 0.05),
      however, transplantation of IL-10 modified BDLSCs improved the ratio
      significantly (P < 0.01). Severe inflammatory response and fibrosis were observed
      in fibrosis group. Inflammatory response was alleviated to some extent in the
      BDLSC group, and the histopathology of BDLSC/IL-10 group was not significantly
      different from that of the control group. Compared to the control group, the
      expression of HGF mRNA and PCNA protein was increased in the fibrosis group (P <
      0.01). The expression of HGF and PCNA was further increased by BDLSCs or IL-10
      modified BDLSCs transplantation. Compared to BDLSCs, IL-10 gene-modified BDLSCs
      were more potent to induce the expression of HGF and PCNA. CONCLUSION:
      Transplantation of IL-10 gene-modified BDLSCs can alleviate hepatic inflammatory
      response and promote liver regeneration in hepatic fibrosis rats.

PMID- 20038334
TI  - [Comprehensive proteome profile of activated rat hepatic stellate cells].
AB  - OBJECTIVE: To profile the protein expression in activated rat hepatic stellate
      cells (HSCs). METHODS: Primary rat HSCs were isolated and cultured in vitro.
      After 10 days in vitro culture, the HSCs were activated. Total protein extracted
      from these activated HSCs were digested, and the obtained peptides were analyzed
      by using online 2D nanoLC-MS/MS. The identified proteins were classified
      according to their distributions and functions. RESULTS: 1014 proteins were
      identified from 50 microg HSCs protein extract, the molecular weights of these
      proteins ranged from 7832 Da to 588,364 Da. Most of these proteins resided in
      nucleus, cytoskeleton, mitochondrion and endoplasmic reticulum. And these
      proteins were mainly involved in nucleic acid metabolism, organelle organization,
      signal transduction and energy generation. Among these proteins, alpha-smooth
      muscle actin, vimentin and desmin were specifically expressed in activated HSCs.
      CONCLUSION: To the best of our knowledge, this is the most comprehensive protein
      expression profile of activated rat HSCs.

PMID- 20038335
TI  - [Function of TTG1A in hepatic stellate cells].
AB  - OBJECTIVE: To investigate the biological functions of TTG1A in liver fibrosis.
      METHODS: Yeast two-hybrid system was used to screen proteins associated with
      TTG1A. Briefly, the coding sequence of TTG1A was cloned into pGBKT7 vector, and
      the recombinant plasmid was transformed into yeast cells AH109 ( a type), then
      these cells were mated with yeast cells Y187 (a type) transformed with human
      leukocyte cDNA library plasmid pACT2. The obtained diploid yeast cells were
      plated on synthetic dropout nutrient medium containing X-alpha-gal for double
      selection. The plasmids from positive colonies were transformed into E.coli and
      sequenced. RESULTS: The recombinant yeast expression vector pGBKT7-TTG1A was
      successfully constructed. Nineteen TTG1A binding proteins, including Homo sapiens
      major histocompatibility complex, class II DP beta 1 (HLA-DPb1), Homo sapiens
      ribosomal protein L30 (RPL30), Homo sapiens nucleophosmin Homo sapiens
      nucleobindin 2 (NUCB2), Homo sapiens ash2, variant Gaucher disease and variant
      metachromatic leukodystrophy, MORF4L1, Homo sapiens ubiquitin-conjugating enzyme
      E2L3 (UBE2L3), APOA1, Homo sapiens lectin, and galectin 1, were identified.
      CONCLUSIONS: This study may help to elucidate the molecular function of TTG1A.

PMID- 20038336
TI  - [A prospective study of the relationship between serum hepatitis B virus DNA and
      the risk of primary liver cancer].
AB  - OBJECTIVE: To determine the relationship between the serum hepatitis B virus
      (HBV) DNA and the risk of primary liver cancer (PLC). METHODS: Farmers aged 30 to
      55 years in Long An county were recruited in this study Blood samples were
      collected and the sera were tested for HBsAg using Enzyme-Linked ImmunoSorbent
      Assay (ELISA), and the HBsAg-positive sera were further tested for viral DNA
      using nested polymerase chain reaction (nPCR). The study subjects were divided
      into three groups. The first group was positive for both HBsAg and HBV DNA. The
      second group was positive for HBsAg but negative for HBV DNA. Age-, sex-,
      residence-matched HBsAg negative controls for group 1 and group 2 were enrolled
      in the third group. The cohort was followed up for four years. RESULTS: The
      positive rate of HBsAg in these farmers was 14.52% (3975/27,379), and the HBV DNA
      positive rate in HBsAg positive subjects was 40.35% (1604/3975). The total PLC
      incidence rate in Group 1 and 2 was 672.45 /100,000 person-years (PY),
      significantly higher than that in Group3 (17.19 /100,000 PY). The relative risk
      (RR) was 39.123, and the 95% confidence interval (CI) was 9.018-159.146. The PLC
      incidence rate of Group 1 (984.03/100,000 PY) was significantly higher than that
      of Group2 (324.38 /100,000 PY). The RR was 3.034, and the 95% CI was 1.795-5.125.
      Multivariate analyses of Group1 and 2 with Cox model showed that sex, age, serum
      HBV DNA, and family history of PLC were independent risk factors of PLC.
      CONCLUSION: HBV DNA and HBsAg positive subjects have a higher chance to develop
      PLC than HBV DNA negative-, HBsAg positive subjects.

PMID- 20038337
TI  - [Risk factors of intrahepatic cholangiocarcinoma: a case-control study].
AB  - OBJECTIVE: To explore the potential risk factors of intrahepatic
      cholangiocarcinoma (ICC) in China. METHOD: A case-control study including 317
      patients with pathologically confirmed ICC and 634 healthy individuals was
      conducted. The cases and controls were matched in age, sex and inhabitancy. Data
      were statistically analyzed by Chi-square test and conditional logistic
      regression. RESULTS: Univariate analysis showed significant difference in HBsAg
      seropositivity, liver cirrhosis, hepatolithiasis, choledocholithiasis and
      schistosomiasis between ICC patients and healthy controls (P < 0.05).
      Multivariate analysis confirmed that HBsAg seropositivity, liver cirrhosis,
      hepatolithiasis and hepatic schistosomiasis were associated with ICC, and their
      adjusted odds ratio (95% confidence interval) were 10.265 (6.676-15.783), 13.101
      (5.265-32.604), 18.242 (3.580-92.958), 18.435 (1.930-176.082), 15.102 (4.607
      49.499) and 11.820 (3.522-39.668), respectively. The incidence of hepatic cyst,
      cholecystolithiasis, hepatic hemangioma, fatty liver, diabetes mellitus, smoking
      and drinking were not significantly different between ICC patients and controls.
      CONCLUSIONS: The HBV infection, liver cirrhosis, hepatolithiasis and hepatic
      schistosomiasis may be the risk factors for ICC in China.

PMID- 20038338
TI  - [Results of 2 years of interferon treatment in HBeAg positive chronic hepatitis
      B].

PMID- 20038339
TI  - [Expression of CD127 on T lymphocyte in peripheral blood of hepatitis B
      patients].

PMID- 20038340
TI  - [Predictive value of virological response on sustained virological response in
      hepatitis C patients].

PMID- 20038341
TI  - [The effect of Rosiglitazone, a PPARgamma receptor agonist, on the NF-kappaB
      signaling pathway in acute hepatic injury induced by LPS].

PMID- 20038342
TI  - [Prevention of CC14-induced liver fibrosis by Periplaneta americana extract].

PMID- 20038343
TI  - [Clinical analysis of seroconversion of HBsAg in chronic hepatitis B patients
      treated with PegIFN alpha-2a].

PMID- 20038344
TI  - [Comparison of two methods for the detection of hepatitis B virus (HBV) DNA in
      serum samples].

PMID- 20038345
TI  - [A case of Budd-Chiari syndrome induced by ethinylestradiol and cyproterone
      acetate].

PMID- 20038346
TI  - [Adiponectin and chronic viral hepatitis].

PMID- 20038347
TI  - [Progress in the diagnosis and treatment of hepatic hydrothorax].

PMID- 20038348
TI  - Addressing technical challenges associated with the FDA's proposed rules for the
      UVA in vitro testing procedure.
AB  - The proposed rules of the Food and Drug Administration (FDA) for the UVA in vitro
      testing procedure were applied to the evaluation of various sunscreen
      formulations and the following technical challenges were observed: when proposed
      roughened quartz substrates were used, the required coefficient-of-variation
      criteria were not met, and the dynamic ranges of the available transmittance
      analyzers were exceeded for sunscreens with high SPF values. In the proposed
      rules, the FDA requested comment regarding the suitability of other possible
      substrates. In this research, two modifications to the FDA's proposed rules were
      evaluated: (a) the use of an alternative substrate, Vitro Skin N-19 (IMS, Inc.)
      instead of roughened quartz substrate and (b) an increase in application time
      from 10 seconds to 30 seconds to ensure a uniform distribution of sunscreen
      product over the application area of the substrate. These two modifications
      allowed meeting the required coefficient-of-variation criteria without exceeding
      the dynamic ranges of the available transmittance analyzers. The modified test
      conditions were utilized for the evaluation of six commercial sunscreens, which
      fulfilled criteria of "medium" or "high" categories-based on their UVAI/UV
      ratios. These findings were in agreement with the statement in the proposed rules
      that the FDA is aware of the difficulty for current sunscreen formulations to
      meet the "highest" category and believes that allowing such a category will
      foster additional research and development in this area. To determine if it was
      possible to achieve a UVA rating greater than 0.95, two experimental sunscreen
      prototypes with bisoctrizole (USAN), bemotrizinol (USAN), avobenzone, and
      octocrylene were tested under the modified test conditions and attained the
      "highest" category. It should be noted that bisoctrizole and bemotrizinol are
      being evaluated by the FDA under TEA and are not permitted in the US at this
      time, but they are approved for use in the rest of the world.

PMID- 20038349
TI  - Fatigue testing of hair-a statistical approach to hair breakage.
AB  - The objective of this work is to describe an alternative approach for assessing
      hair breakage. The methodology involves the repeated application of force,
      together with an evaluation of the number of cycles required before breakage-an
      approach often termed fatigue testing. The technique provides novel results,
      which appear to indicate more sizable differences between samples than arise from
      conventional constant-rate extension experiments. For example, results illustrate
      a substantially higher tendency for breakage in Afro hair as compared to
      Caucasian hair-a conclusion that appears in line with consumer experiences. Also,
      findings suggest a substantially larger contribution from the relative humidity
      of the environment to the propensity for breakage under these conditions.The
      fatigue approach also lends itself to a novel means of data analysis in which
      breakage is treated as a statistical variable rather than as a mechanical
      parameter. By performing Weibull analysis of the data, a characteristic lifetime
      and a shape parameter are obtained to characterize the data, while survival
      probability plots can be generated to predict the propensity for breakage under a
      specific set of conditions.

PMID- 20038350
TI  - The effect of cationic polymer treatment on adhesion of iron oxide to eyelashes.
AB  - The aim of this study was to investigate the effect of iron oxide application on
      improving the volume of eyelashes. Iron oxide, having a negative surface charge
      in its natural form, was coated with commercial cationic polymers to increase its
      adhesion. The iron oxides coated with different types and concentrations of these
      polymers were incorporated into a basic mascara formula to test their volume
      effects by means of the weight difference of eyelashes.The results indicated that
      the type and concentration of coating materials affect the surface zeta potential
      and particle cluster size of iron oxides. The type of cationic polymer,
      especially, was shown to modify both factors of iron oxide. The obtained results
      also suggested that the volume effect of mascara increases with a higher positive
      surface zeta potential and a smaller particle cluster size of the coated iron
      oxides.

PMID- 20038351
TI  - Study and description of hydrogels and organogels as vehicles for cosmetic active
      ingredients.
AB  - Cellulite, a clinical syndrome mainly affecting women, involves specific changes
      in conjunctive dermic and subcutaneous tissue, leading to vascular and
      hypertrophic alterations in adipose tissues and the consequent alteration of
      tissue structure. This paper describes the design of hydrogels and pluronic
      lecithin organogels elaborated as vehicles of Aloe vera (Aloe vera linne) and
      Hydrocotyle asiatica (Centella asiatica) for the treatment of cellulite. The
      objective of this work was to carry out a complete evaluation of the proposed
      formulae through the study of the organoleptic and rheological properties of the
      formulae. Our work revealed that, in appearance, hydrogels show better
      organoleptic characteristics than organogels. On the other hand, from a
      rheological point of view, both hydrogels and organogels display a plastic
      behavior. However, the main difference between the two is that the more complex
      internal structure of the organogel bestows it with more viscosity. Finally, in
      vitro tests with Franz-type diffusion cells revealed that the release of cosmetic
      active principle from the tested excipients was appropriate, both in terms of
      magnitude and velocity.

PMID- 20038352
TI  - Changes in structure and geometric properties of human hair by aging.
AB  - To clarify hair changes by aging, the effect of age on hair properties was
      investigated from macro- to microscopic view points. Sensory hair luster tests
      were performed on 230 Japanese females from 10 to 70 years of age, revealing that
      hair luster decreases with age. The age dependence of the hair diameter and the
      ellipticity of the hair cross section could not explain luster reduction by
      aging. It has been determined that an irregular increase in fiber curvature
      occurs with age and is a cause of luster reduction with aging. A detailed
      structural analysis by synchrotron radiation microbeam X-ray diffraction revealed
      that the inhomogeneity in the lateral distribution of the hair microstructure
      increased with age and relates to the irregular increase in curvature. Such an
      increase in curvature is one of the important factors that leads to a poor
      alignment of hairs and luster reduction, and is related to the appearance of
      aging hair.

PMID- 20038359
TI  - [Actas Dermo-Sifiliograficas 1951-1960: thoughts from a decade past. Interview by
      Esteban Dauden Tello].

PMID- 20038360
TI  - [Congenital epidermolysis bullosa: a review].
AB  - Epidermolysis bullosa is a group of hereditary diseases affecting 1 in 17,000
      live births worldwide. It consists of blistering of the skin and mucous membranes
      in response to minimal trauma. The disorder seriously affects the patient's
      quality of life. Diagnosis is based on immunofluorescence mapping and electron
      microscopy. Treatment is symptomatic, although new cellular and molecular
      therapies are currently under investigation. This review covers aspects of the
      molecular biology, clinical presentation, diagnosis, and treatment of
      epidermolysis bullosa relevant to improving the care for affected patients.

PMID- 20038361
TI  - [Skin manifestations of toxic syndrome due to denatured rapeseed oil].
AB  - This article offered an extensive description of the clinical and pathological
      features and time-course of the skin manifestations of toxic syndrome caused by
      denatured rapeseed oil, also known as toxic oil syndrome. This new condition
      occurred in Spain in 1981 and was due to the ingestion of rapeseed oil intended
      for industrial use that had been denatured with anilines and subsequently refined
      and sold fraudulently as olive oil. In total, 20,000 cases and 400 deaths were
      reported. The disease affected mainly women, particularly in the late stages. In
      the acute phase, the predominant skin manifestations were toxic-allergic rashes
      reminiscent of allergic urticaria in the dermatopathologic study. In
      approximately 25% of cases, the patients' skin subsequently took on an edematous
      appearance, with pigmentary abnormalities shown to be related to cutaneous
      mucinosis. Finally, a characteristic sclerodermatous condition would develop that
      tended to improve spontaneously. The constant presence of mast cells in all
      biopsies and the development of mastocytosis in several patients pointed to an
      important role for these cells in the pathogenesis of the condition. This was
      subsequently confirmed in other sclerodermatous processes. In 1989, eosinophilia
      myalgia syndrome caused by toxins present in tryptophan food supplements was
      reported in the United States. This syndrome resembled toxic oil syndrome in many
      ways and demonstrated that mucinosis and toxic sclerodermatous processes do
      exist.

PMID- 20038362
TI  - [Historical critique of Spanish venereology].
AB  - The journal's centenary this year provides a good chance to analyze the changes
      that have taken place in Spanish dermatovenereology. At such an important
      milestone, the tendency is to highlight major scientific achievements while
      neglecting the many more mundane years. This historical critique aims to explain
      the merit of our mentors--given the adverse and unstable scientific, economic,
      and social situation--in merely aiming to copy the best of other more stable
      countries to create dermatology structures and programs from which we have all
      since benefited. Likewise, a more recent period and one about which less has been
      written--the 1980s--is evoked.

PMID- 20038363
TI  - [Use of www.dermatoweb.net to support undergraduate teaching of dermatology].
AB  - Dermatoweb is a website to aid undergraduate dermatology training. It includes
      the dermatology program of the Lerida Faculty of Medicine, and is based
      principally on clinical presentations, tables with the differential diagnosis of
      the 20 most common reasons for dermatologic consultation, about 200 clinical test
      cases to stimulate self-training, and a subject list with the 32 topics that make
      up the dermatology syllabus in many faculties of medicine. Thanks to this
      website, some of our students achieve high marks in dermatology despite hardly
      coming to classes. In addition, therapeutic guidelines for the common dermatoses
      can be found on the site, and an atlas with more than 5,300 photographs and
      almost 100 videos on the more common dermatological procedures; these can serve
      as a visual aid for family doctors, residents in dermatology in the initial
      years, and practicing dermatologists.

PMID- 20038364
TI  - [Key diagnostic features and treatment of subungual glomus tumor].
AB  - Glomus tumor was first described by Wood in 1812 and named as such by Masson in
      1924. It is a rare benign vascular tumor of the neuromyoarterial glomus. The
      triad of cold intolerance, intense paroxysmal pain, and well-defined site of pain
      is characteristic of the tumor. Approximately 80 % of lesions are found on the
      upper limbs, mostly under the nails. Between 2005 and 2008, 7 patients with this
      disease were seen in our department. Diagnosis was confirmed by histology after
      excision. We review the clinical features, complementary diagnostic tests, and
      main surgical techniques described.

PMID- 20038365
TI  - [Severe adult atopic dermatitis: treatment with mycophenolate mofetil in 8
      patients].
AB  - BACKGROUND: Atopic dermatitis (AD) includes severe forms that can be refractory
      to various systemic treatments. Mycophenolate mofetil (MMF) has been found to be
      useful in patients with severe forms of AD and to have fewer side effects than
      long-term treatment with oral corticosteroids or cyclosporine. OBJECTIVES: To
      evaluate the efficacy and adverse effects of MMF in patients seen in our skin
      allergy unit with severe adult AD refractory to other systemic treatments.
      METHODS: We performed a retrospective study of 8 patients with severe adult AD
      treated with MMF, analyzing the baseline characteristics, previous treatments
      used by the patients, and the outcome and adverse effects of treatment with MMF.
      RESULTS: Five patients treated with MMF showed improvement in the fourth week of
      treatment. In addition, 5 of the 8 patients presented a clear, long-term
      improvement in their disease. Remission of AD occurred in 1 patient, making it
      possible to discontinue MMF; this patient remains stable with no relapses after 4
      months without treatment. The other 4 patients continue on maintenance therapy.
      Three patients continued to have frequent acute outbreaks of AD despite treatment
      with MMF for 16 to 72 weeks. All patients tolerated the treatment and there were
      few adverse effects. CONCLUSIONS: MMF can be an effective option in selected
      patients with severe forms of atopic dermatitis. Although the response is not as
      rapid as with oral corticosteroids or cyclosporine, it can be used for
      maintenance treatment with good clinical control and few adverse effects.

PMID- 20038366
TI  - [Erysipelas and cellulitis: a retrospective study of 122 cases].
AB  - BACKGROUND: Erysipelas and cellulitis are relatively common cutaneous infections
      that can sometimes be the cause of a prolonged hospital admission. The objective
      of this study was to determine the most relevant epidemiologic factors and their
      influence on the length of hospital stay, comparing our results with those of
      previous studies. MATERIAL AND METHODS: We performed a retrospective,
      observational, cross-sectional study of 122 patients admitted over a 5-year
      period to the dermatology department of our hospital with a diagnosis of
      erysipelas or cellulitis. RESULTS: Patients with a diagnosis of erysipelas or
      cellulitis represented 8.6% of all admissions during the study period. The mean
      age was 58.93 years and the female to male ratio was 1.06:1. The most common site
      of involvement was on the legs (76.22%). Overweight or obesity was present in
      42.6% of patients and tinea pedis was detected in 33.6% of cases. A skin abscess
      developed in 7.4% of cases. The mean length of admission was 10.20 days; length
      of stay increased with age and with the erythrocyte sedimentation rate (ESR) on
      admission (P < .01 for both differences). CONCLUSIONS: We confirm general
      epidemiologic factors such as sex and age distributions, predominant site, past
      history, and length of hospital stay. In view of their predictive value for the
      length of hospital stay, we propose that age and the ESR on admission should be
      considered to be indirect indicators of disease severity.

PMID- 20038368
TI  - [Photodynamic therapy for actinic cheilitis].
AB  - Actinic cheilitis is a subtype of actinic keratosis that mainly affects the lower
      lip and has a higher risk of malignant transformation. Its location on the labial
      mucosa influences the therapeutic approach. Vermilionectomy requires local or
      general anesthetic and is associated with a risk of an unsightly scar, and the
      treatment with 5-fluorouracil or imiquimod lasts for several weeks and the
      inflammatory reaction can be very intense. A number of authors have used
      photodynamic therapy as an alternative to the usual treatments. We present 3
      patients with histologically confirmed actinic cheilitis treated using
      photodynamic therapy with methyl aminolevulinic acid as the photosensitizer and
      red light at 630 nm. The clinical response was good, with no recurrences after 3
      to 6 months of follow-up. Our experience supports the use of photodynamic therapy
      as a good alternative for the treatment of actinic cheilitis.

PMID- 20038369
TI  - [Dermoscopic characterization of 3 cases of fibroepithelioma of Pinkus].
AB  - Fibroepithelioma of Pinkus is considered to be a rare variant of basal cell
      carcinoma with well-defined histopathological features. Clinical diagnosis often
      requires differentiation from benign lesions such as acrochordon, intradermal
      melanocytic nevus, neurofibroma, seborrheic keratosis, and even malignant lesions
      such as amelanotic melanoma. Dermoscopy of this type of lesion is not extensively
      described in the literature, though it usually presents certain specific
      characteristics that suggest the diagnosis and, therefore, an appropriate
      therapeutic approach. We present 3 cases of fibroepithelioma of Pinkus,
      describing their clinical, dermoscopic, and histopathological features.

PMID- 20038370
TI  - [Erythematous papules on the upper chest wall].

PMID- 20038371
TI  - [Linear erythema on the face of a boy].

PMID- 20038372
TI  - [Widespread idiopathic comedones and lichen ruber planus: clinical and
      histological association].

PMID- 20038373
TI  - [A case of transient rectangular alopecia after aneurysm embolization].

PMID- 20038374
TI  - [Generalized linear porokeratosis limited to one side of the body].

PMID- 20038375
TI  - [Hair transplantation in triangular temporal alopecia].

PMID- 20038376
TI  - [Lichen planus and lichen striatus: opposite ends of a single spectrum?].

PMID- 20038377
TI  - [Unilateral allergic contact dermatitis of the eyelid caused by Iopimax].

PMID- 20038378
TI  - [Perineal nodular induration in cyclists].

PMID- 20038379
TI  - [Perianal verrucous papules in a patient with Bannayan-Riley-Ruvalcaba syndrome].

PMID- 20038380
TI  - [Forever yours].

PMID- 20038381
TI  - [Burnout syndrome in different intensive care units].
AB  - OBJECTIVES: To determine the prevalence of the professional burnout syndrome in
      health care personnel of different Intensive Care Units (ICUs). To know the
      association between burnout, its dimensions and sociodemographic-laboral
      variables. To compare the dimensions of burnout, characteristics of the personnel
      and of the patients of the different ICUs. MATERIAL AND METHODS: Analytic,
      comparative, cross-sectional study performed in the ICU of a tertiary hospital in
      November 2006 performed in a sample of 289 professionals. The Maslach Burnout
      Inventory questionnaire and sociodemographic-laboral variables were provided. The
      following were evaluated in the ICUs: Therapeutic Intervention Scoring System
      (TISS), Nine Equivalents of Nursing Manpower Use Score (NEMS), mortality, stay,
      isolations and travel of third parties. The chi2 test, Fischer test, Kruskall
      Wallis test and multivariate logistic regression analysis were used. RESULTS: A
      total of 73% of the workers answered. Ages ranged from 37 +/- 9 and 81% were
      women. The prevalence of burnout was 14%, this affecting 16% of the nurses, 14%
      of residents, 13% physicians and 10% auxiliary workers. Burnout was associated to
      low professional satisfactions, relationship with regular colleagues, low work
      recognition and time worked and experience in the ICU to high emotional
      tiredness, with a p < 0.05. In a polyvalent ICU, higher values of the following
      were obtained: TISS 42 +/- 11, NEMS 35 +/- 10, mortality 18%, stay 5 +/- 9,
      isolation 21%, burnout syndrome 17%, elevated emotional tiredness 49%, elevated
      depersonalization 63% and low professional performance 44%. CONCLUSIONS: The
      prevalence of the burnout syndrome in our sample was 14%, those being affected
      most being the nursing professionals. We detected elevated levels of
      depersonalization and middle levels of emotional tiredness and professional
      performance. The variables related with professional burnout syndrome were low
      professional satisfaction, relationship with regular colleagues, low work
      recognition, and elevated emotional tiredness in the more expert personnel. The
      ICU with the greatest prevalence of burnout during the month studied attended
      patients with greater TISS, NEMS, mortality, stay and isolations.

PMID- 20038382
TI  - [Drawing of blood and anemia of the critical patient].
AB  - OBJECTIVE. To determine the hemoglobin level variations in non-bleeding patients,
      its possible relationship with the blood volume drawn and number of extractions.
      METHODS: An observational, prospective study conducted from April to August 2007.
      Hemoglobin values during the ICU stay, blood volume drawn in each phlebotomy,
      fluid balance, APACHE II and other demographic variables were determined.
      RESULTS: One hundred and twenty four patients were studied. Of these, 59.7%
      experienced a mild decrease of hemoglobin levels (< 2g/dl) whereas 21.8%
      presented a more severe reduction (> 2g/dl). These decreases were correlated with
      the blood volume withdrawn and number of phlebotomies performed (r= 0.557, p <
      0.000). There was no significant relationship between fluid balance and decrease
      in hemoglobin. CONCLUSION. Anemia in critical ill patient seems to be related to
      blood volume drawn and number of phlebotomies.

PMID- 20038383
TI  - [Analysis of the web pages of the intensive care units of Spain].
AB  - In order to determine the Intensive Care Units (ICU) of Spanish hospitals that
      had a web site, to analyze the information they offered and to know what
      information they needed to offer according to a sample of ICU nurses, a cross
      sectional observational, descriptive study was carried out between January and
      September 2008. For each ICU website, an analysis was made on the information
      available on the unit, its care, teaching and research activity on nursing.
      Simultaneously, based on a sample of intensive care nurses, the information that
      should be contained on an ICU website was determined. The results, expressed in
      absolute numbers and percentage, showed that 66 of the 292 hospitals with ICU
      (22.6%) had a web site; 50.7% of the sites showed the number of beds, 19.7% the
      activity report, 11.3% the published articles/studies and followed research lines
      and 9.9% the organized formation courses. 14 webs (19.7%) displayed images of
      nurses. However, only 1 (1.4%) offered guides on the actions followed. No web
      site offered a navigation section for nursing, the E-mail of the chief nursing,
      the nursing documentation used or if any nursing model of their own was used. It
      is concluded that only one-fourth of the Spanish hospitals with ICU have a web
      site; number of beds was the data offered by the most sites, whereas information
      on care, educational and investigating activities was very reduced and that on
      nursing was practically omitted on the web pages of intensive care units.

PMID- 20038384
TI  - [Monitoring of deep sedation. The BIS(R) monitor].
AB  - Adequate monitoring of analgesia and sedation should be one of the main goals in
      the Intensive Care Units. Once the analgesia is assured, the correct dosage of
      the sedatives will depend on the correct monitoring of the sedation level. For
      years, clinical scales have been used to evaluate the sedation level. These
      scales are appropriate for the evaluation of mild sedation but they cannot
      correctly evaluate deeply sedated patients or those patients who require
      continuous intravenous administration of neuromuscular blockade agents. In this
      chapter, we review the most used monitor to control the adequate level of
      sedation in the Intensive Care Units as well as the BIS(R) Monitor, which is the
      one recommended by the Analgesia and Sedation Work Group of the Spanish Society
      of Critical Care Medicine (SEMICYUC).

PMID- 20038385
TI  - [Review of knowledge to care for patients with respiratory problems].

PMID- 20038386
TI  - [Review of knowledge on prophylaxis of the infection in the critical patient.
      Responses to the test in Vol. 20 No. 3].

PMID- 20038387
TI  - [Swine flu (H1N1) pandemic: challenges and repercussions for the health care
      system].

PMID- 20038388
TI  - [Establishment of a quality indicator for pharmaceutical care].
AB  - OBJECTIVE: To establish a quality indicator for pharmaceutical care in an
      integral system for personalized medication dispensing (ISPMD) with electronic
      prescription. METHODS: Descriptive transversal study. PERIOD: 2007. On a daily
      basis, we revised the pharmaceutical treatment of patients admitted to hospital
      units with ISPMD. STUDY VARIABLES: a) suitability of pharmaceutical
      interventions: important or very important; b) acceptance of those interventions.
      The LASER method was used to identify patients with improvement opportunities.
      RESULTS: In absolute terms (mean +/- SD): important pharmaceutical interventions,
      26.6 +/- 14.8; very important, 31.5 +/- 24.6; acceptance, 57.5 +/- 25.9.
      Percentages (95 % CI): pharmaceutical interventions: important, 33.7 (9.3-58.0);
      very important, 39.80 (17.7-62.2); acceptance, 72.6 (64.7-80.5). CONCLUSIONS:
      Implementation of the quality indicator for pharmaceutical care allowed us to
      evaluate the clinical significance and the acceptance rate of the pharmaceutical
      care being provided.

PMID- 20038389
TI  - [Study of rituximab efficacy, cost, safety, and compliance of its package leaflet
      in a tertiary hospital].
AB  - INTRODUCTION: The appearance of monoclonal antibodies, and specifically,
      rituximab, has provided a new approach to treating non-Hodgkin's lymphomas and
      rheumatoid arthritis. The purpose of this study is to analyse whether this drug
      is used according to its package leaflet in clinical practice, evaluate the
      treatment's efficacy and determine its cost. METHODS: Ambispective, observational
      single-centre study of medication use set up as a prescription evaluation for the
      indication of rituximab in a tertiary hospital between March 2003 and 31 December
      2007. RESULTS: 82 of the 221 patients who were treated (37.1 %) received the drug
      for a condition that does not appear in the package leaflet. 51.1 % and 27.5 % of
      response and progression were registered for approved diagnoses and 34.9 % and 47
      % for non-approved diagnoses; the death rate was 25.3 % and 41.5 % respectively.
      The mean cost per treatment episode was the highest for idiopathic
      thrombocytopenic purpura (11,683 euro), whilst the highest treatment cost per
      patient was associated with follicular lymphoma (15,940 euro). DISCUSSION: We
      found that the main cause of the high rate of non-compliance with the package
      leaflet is patient lack of response to standard treatments, together with
      clinical practice guides that support the use of rituximab for conditions other
      than those for which it is indicated. Nevertheless, most of the clinical trials
      evaluating the efficacy of rituximab for these unauthorized diagnostic profiles
      have poor methodology, are in phase II, are open studies, have low patient
      numbers, or in some cases, are not comparative.

PMID- 20038390
TI  - [Detecting adverse drug events during the hospital stay].
AB  - INTRODUCTION: The principal objective was to determine the incidence rate of
      adverse drug events (ADEs) in hospitalised patients and evaluate the event
      prevention percentage. METHODS: Multi-centre, prospective observational study
      lasting four months, performed in five hospitals providing different levels of
      care. We included all adult patients who were admitted to one of the selected
      centres for longer than 48 hours and who required pharmacological treatment. ADEs
      were identified by direct observation and the use of previously defined alarm
      signals. The Karch-Lasagna scale was used to determine the causality
      relationship, and the Schumock and Thornton questionnaire adapted by Otero was
      used to evaluate ADE preventability. Preventable drug-induced adverse events were
      classified according to the taxonomy that the Ruiz-Jarabo 2000 group defined, and
      coordinated by ISMP-Spain. RESULTS: We included 1,550 patients, 159 of whom
      experienced at least one ADE (10.3 %). The preventability percentage was 51.6 %,
      which represented 5.3 % of the total sample. The endocrine system (34.8 %) and
      the cardiovascular system (20.7 %) were the most affected by preventable ADEs.
      Antibiotics were responsible for 16.5 % of all ADEs. 9.3 % of all preventable
      ADEs were triggered by use of opiates. The vast majority of preventable ADEs
      (36.3 %) resulted from omitting a necessary medication. Only 4.4 % of preventable
      ADEs are considered to be serious. CONCLUSIONS: There is a high incidence rate of
      ADEs during patients' hospital stay (10.3 %), and half of them (51.6 %) could
      have been prevented. Implementation of an automatic alarm system and certain best
      practices for problem spots along the care circuit will help detect and avoid
      preventable ADEs.

PMID- 20038391
TI  - [Pharmacogenetic analysis of the absorption kinetics of cyclosporine in a
      population of Spanish cardiac transplant patients].
AB  - OBJECTIVE: To determine how single nucleotide polymorphisms located on genes
      MDR1, CYP3A4 and CYP3A5 affect the absorption kinetics of cyclosporine in cardiac
      transplant patients. METHOD: We selected a sample of 30 adult patients having
      previously undergone a primary cardiac transplant and who had received
      cyclosporine as an immunosuppressant. During the first month after the
      transplant, we performed a pharmacokinetic study of each patient to determine
      values in the cyclosporine concentration area under the 12-hour curve, steady
      state cyclosporine concentration, maximum cyclosporine concentration, and time to
      reach that concentration. Single nucleotide polymorphisms were genotyped in all
      patients: MDR1 3435C > T, CYP3A4-390A > G and CYP3A5 6986A > G. RESULTS: Being a
      carrier of the T-allele for polymorphism MDR1 3435C > T is associated with higher
      values in the cyclosporine concentration area under the 12-hour curve (p = 0.01)
      and in steady-state cyclosporine concentration (p = 0.05), compared with those
      from patients who do not carry that allele. DISCUSSION: Our results show that
      genotype differences in MDR1 3435C > T can explain part of the variability in
      cyclosporine absorption among individuals in the population of Spanish cardiac
      transplant recipients.

PMID- 20038392
TI  - [Study of drug dose calculation for morbidly obese patients].
AB  - INTRODUCTION: The objective of this study is to analyse the appropriateness and
      characteristics of drug dose calculation for hospitalised, morbidly obese
      patients. METHODS: Retrospective, descriptive study of dose calculations for
      drugs prescribed to hospitalised, morbidly obese patients in a tertiary hospital
      in 2007. The recommendations prepared by the Pharmacy division are used as a
      standard. RESULTS: We included 62 patients. The mean number of medications
      prescribed per patient was 12.1 (4-39), and an average of 2.4 (1-10) are listed
      in the recommendations. A total of 135 drugs were prescribed. Dose calculations
      for 81 of the above (60 %) coincided with recommendations and 54 (40 %) did not;
      there were 51 cases of underdosing and three cases of overdosing. DISCUSSION:
      Improper dosing was detected for prescriptions in the systemic antibiotic and
      antithrombin drug groups, with underdosing being more common than overdosing.

PMID- 20038393
TI  - [Interferon alpha 2b eyedrops as treatment of conjunctival intraepithelial
      neoplasia].

PMID- 20038394
TI  - [Pralidoxime for organophosphate poisoning: regarding two paediatric cases].

PMID- 20038395
TI  - [Safety and effectiveness of combining clopidogrel and proton pump inhibitors].

PMID- 20038396
TI  - [Controversy regarding the concomitant use of clopidogrel and proton pump
      inhibitors (PPI)].

PMID- 20038398
TI  - Research productivity among nations.

PMID- 20038397
TI  - [Desensitization to tipranavir caused by toxicodermia].

PMID- 20038399
TI  - Returning patients after primary percutaneous coronary angioplasty: the (re)
      TRANSFER AMI.

PMID- 20038400
TI  - Sex hormone-binding globulin and heart failure: a passive carrier of steroid
      hormones or an active hormone itself?

PMID- 20038401
TI  - Safety and feasibility of returning patients early to their originating centers
      after transfer for primary percutaneous coronary intervention.
AB  - INTRODUCTION AND OBJECTIVES: At present, little information is available on
      returning patients with ST-elevation myocardial infarction (STEMI) to their
      originating centers after transfer for primary percutaneous coronary intervention
      (PPCI). The objective of this study was to evaluate the safety and feasibility of
      the early return of these patients to their originating centers. METHODS: The
      cohort study involved 200 consecutive STEMI patients (age 62+/-13 years, 83%
      male) who were returned to their originating centers after PPCI. They were
      compared with a group of 297 patients with similar characteristics from our
      healthcare catchment area. The length of stay in the intervention hospital and
      major adverse cardiovascular events occurring within 30 days were recorded.
      RESULTS: The median length of stay in the intervention hospital was 8 hours. No
      adverse events occurred during transport in the group who returned to their
      originating centers. At 30-day follow-up, no significant difference was observed
      between patients who returned and the control group in either mortality (1.0% vs.
      3.7%; P=.064), readmission (5.0% vs. 4.5%; P=.657), ischemic complications (2.5%
      vs. 2.0%; P=.721), re-catheterization (5.0% vs. 2.5%; P=.112), stroke (1% vs. 1%;
      P=.936) or the composite end-point (11% vs. 9.2%; P=.540). Multivariate analysis
      showed that returning patients after PPCI was not associated with a significantly
      greater number of major adverse cardiovascular events (odds ratio=1.32; 95%
      confidence interval, 0.62-2.80). CONCLUSIONS: The early return of patients with
      low-risk STEMI to their originating centers after PPCI was safe and feasible.

PMID- 20038402
TI  - Effect of antibiotic treatment in patients with postimplantation syndrome after
      aortic stent placement.
AB  - INTRODUCTION AND OBJECTIVES: Postimplantation syndrome that can develop after
      stent placement is characterized by fever, leukocytosis and an elevated C
      reactive protein level or by coagulation disturbances, or by a combination of
      these features. It is a transient condition that frequently appears following
      endovascular treatment. At present, no data are available on the effect of
      antibiotics on postimplantation syndrome after placement of a thoracic
      endoprosthesis. METHODS: This prospective single-center study involved 40
      patients. Of these, 20 received peri-interventional (for 24 hours) antibiotic
      treatment with cefuroxime, 20 mg/ kg three times per day, while 20 received
      prolonged (for 7 days) treatment at the same dosage. Peripheral blood samples
      were taken before the intervention and 6 h, 12 h, 24 h, 48 h, 3 days, 5 days, and
      7 days after. RESULTS: There was no significant difference in clinical or
      laboratory findings between the two treatment strategies, and subsequent changes
      in clinical and laboratory parameters over time were similar in the two groups.
      All parameters returned to baseline values within 7 days. CONCLUSIONS: Prolonging
      antibiotic treatment beyond the day of endovascular intervention was not observed
      to provide any short- or long-term clinical benefit in patients with
      postimplantation syndrome, given that all blood samples were sterile.

PMID- 20038403
TI  - Comparison of iodixanol and ioversol for the prevention of contrast-induced
      nephropathy in diabetic patients after coronary angiography or angioplasty.
AB  - INTRODUCTION AND OBJECTIVES: This study was designed to compare differences in
      the incidence of contrast-induced nephropathy (CIN) and changes in serum
      creatinine (SCr) level following iso-osmolar iodixanol or low-osmolar ioversol
      administration in diabetic patients undergoing coronary angiography, with or
      without percutaneous coronary intervention (PCI). A number of studies have
      indicated that iodixanol reduces the risk of CIN in patients with renal
      impairment, with or without diabetes. Diabetic patients may have some degree of
      renal dysfunction despite having a normal SCr level. METHODS: The study included
      250 consecutive diabetic patients undergoing coronary angiography with or without
      PCI. Those enrolled during the first 7 months of the study received ioversol and
      those enrolled during the following 11 months received iodixanol. The primary
      study endpoint was the incidence of CIN. Secondary objectives were to identify
      independent predictors of CIN and to determine the mean increase in SCr 72 hours
      after contrast injection. RESULTS: The overall incidence of CIN was 5.6%. The
      incidence of CIN was significantly lower with iodixanol than with ioversol (2.5%
      vs. 8.3%, respectively; odds ratio [OR]=0.255; 95% confidence interval [CI],
      0.068-0.952; P=.047). A low estimated glomerular filtration rate (60.8+/-29
      mL/min per 1.73 m2 in those with CIN vs. 75.3+/-25 mL/min per 1.73 m2 in those
      without; OR=0.975; 95% CI, 0.952-0.997; P=.03) and ioversol use were independent
      predictors of CIN. CONCLUSIONS: In diabetic patients undergoing diagnostic
      coronary angiography with or without PCI, the iso-osmolar contrast medium
      iodixanol was associated with a lower incidence of CIN than low-osmolar ioversol.

PMID- 20038404
TI  - Sex hormone-binding globulin: a new marker of disease severity and prognosis in
      men with chronic heart failure.
AB  - INTRODUCTION AND OBJECTIVES: Sex hormone-binding globulin (SHBG) is a key
      regulator of the actions of anabolic steroids. Chronic heart failure (HF) has
      been associated with anabolic steroid deficiency, but its relationship with SHBG
      is not known. METHODS: The study involved 104 men (53+/-11 years) with HF (i.e.
      left ventricular ejection fraction [LVEF] <40%) attending a specialist clinic on
      optimum treatment and in a stable condition. At enrolment, the median and
      interquartile range (IQR) SHBG level was determined, associated hormone levels
      were measured, and known risk factors were recorded. The study end-point was
      cardiac death within 3 years. RESULTS: At enrolment, the SHBG level (median 34.5
      nmol/L, IQR 27-50 nmol/L) was correlated with the N-terminal probrain natriuretic
      peptide level (r=0.271, P=.005), LVEF (r=-0.263, P=.007), body mass index (r=
      0.199, P=.020) and total testosterone level (r=0.332, P=.001). The median SHBG
      level was higher in the 16 patients (15.4%) who died, at 48.5 nmol/L (IQR 36-69.5
      nmol/L) vs. 33 nmol/L (IQR 25.3-48.7 nmol/L; P=.001), and a high level was
      associated with an increased risk of death (hazard ratio [HR]=1.045, 95%
      confidence interval [CI] 1.021-1.069; P< .001). The association remained
      significant after adjustment in Cox multivariate regression modeling, at HR=1.049
      (95% CI 1.020-1.079; P=.001). Analysis by SHBG tertiles showed mortality was 30%
      in the third tertile, 14% in the second, and 4% in the first (log rank 0.007;
      HR=3.25, 95% CI 1.43-7.34; P=.004). CONCLUSIONS: The SHBG level correlated with
      measures of HF severity and was associated with a higher risk of cardiac death.
      Further studies are needed to clarify whether SHBG plays a role in HF
      pathophysiology.

PMID- 20038405
TI  - In-hospital prognosis of prosthetic valve endocarditis after urgent surgery.
AB  - INTRODUCTION AND OBJECTIVES: Prosthetic valve endocarditis is associated with
      high morbidity and mortality, particularly when urgent surgery is needed. The
      identification of factors that predict a poor prognosis is the first step in
      improving outcomes. The study objectives were to characterize patients with
      prosthetic valve endocarditis who need urgent surgery and to identify factors
      that predict in-hospital mortality in this high-risk group. METHODS: From a
      database of 648 consecutive patients with infective endocarditis diagnosed
      between 1996 and 2006 at four tertiary-care centers with cardiac surgery
      facilities, 46 patients with left-sided prosthetic valve endocarditis who needed
      urgent surgery were identified. A retrospective study was carried out to
      determine these patients' main characteristics and to identify predictors of in
      hospital mortality. RESULTS: The main indications for urgent surgery were heart
      failure (57%) and persistent infection (33%). In-hospital mortality was 41%.
      Factors significantly associated with a poor prognosis were fever at admission,
      persistent infection, positive blood cultures, persistently positive cultures,
      and echocardiographic evidence of vegetations (P< .05). No specific microorganism
      was associated with a poor prognosis. CONCLUSIONS: Prosthetic valve endocarditis
      was associated with high mortality when urgent surgery was needed. Although heart
      failure was the principle reason for urgent surgery, it did not lead to a worse
      in-hospital prognosis. The presence of vegetations and uncontrolled infection
      were the main factors associated with higher in-hospital mortality in patients
      with left-sided infective endocarditis who needed urgent surgery.

PMID- 20038406
TI  - Diastolic dysfunction in diabetic patients assessed with Doppler
      echocardiography: relationship with coronary atherosclerotic burden and
      microcirculatory impairment.
AB  - INTRODUCTION AND OBJECTIVES: Diabetes mellitus (DM) is associated with the
      development of both impaired left ventricular diastolic function (LVDF) and
      pathological changes in the coronary macro- and microcirculation. The aim of this
      study was to investigate the relationship between these manifestations of
      diabetic heart disease. METHODS: The severity of atherosclerosis in the left
      anterior descending coronary artery (LAD) was quantified using intravascular
      ultrasound (IVUS) in 13 patients with DM and ischemic heart disease. The coronary
      flow velocity reserve (CFVR), instantaneous hyperemic diastolic velocity pressure
      slope index (IHDVPS) and zero-flow pressure were derived from digital
      intracoronary pressure and flow velocity measurements. The relationships between
      indices of LVDF (i.e. E/A and E/e' ratios) and intracoronary measurements were
      assessed. RESULTS: The left ventricular ejection fraction was 66+/-7%, and the
      LVDF indices were: E/A=0.92+/-0.38 and E/e'=9.90+/-2.80. There was a direct
      proportional relationship (r=0.62; P=.02) between E/e' and coronary resistance
      (1.93+/-0.74 mmHg/s) and an inverse proportional relationship (r=-0.64; P=.02)
      between E/e' and IHDVPS (1.56+/-0.50 cm/s/mmHg). However, no significant
      relationship was found between either LVDF index and CFVR (2.43+/-0.56) or
      coronary zero-flow pressure (40.41+/-10.66 mmHg). The volume of atheroma in the
      proximal 20 mm of the LAD (179.34+/-57.48 .l, with an average plaque area of
      8.39+/-2.20 mm2) was not related to either LVDF index. CONCLUSIONS: In patients
      with DM and coronary atherosclerosis, there appeared to be a relationship between
      LVDF impairment (assessed by the E/e' ratio) and structural changes in the
      microcirculation.

PMID- 20038407
TI  - Cardiovascular scientific production in Spain and in the European and global
      context (2003-2007).
AB  - INTRODUCTION AND OBJECTIVES: The publication of research articles has increased
      considerably in recent years in all biomedical fields. The present study examines
      the position of Spanish quality research in cardiology in the European and world
      context, and its evolution during the 5-year period 2003-2007. METHODS: Using the
      Science Citation Index Expanded of Thomson Reuters as data source, we compared
      Spanish cardiovascular scientific production with that of the rest of countries
      in the European Union and of the most important countries worldwide, along with
      relative productivity as per number of inhabitants and Gross Domestic Product,
      and the number of citations in the journals of the <<Cardiac and Cardiovascular
      Systems>> area of the Journal Citation Reports (CCS-JCR). RESULTS: Spain ranks
      sixth in the European Union and ninth worldwide in scientific production (tenth
      worldwide if only the journals of the first quartile of the CCS-JCR area are
      considered). As regards the number of citations received, Spain ranks seventh in
      the European Union and eleventh worldwide. In terms of relative productivity as
      per number of inhabitants and Gross Domestic Product, the Spanish ranking is less
      favorable (positions 15 and 18, respectively). CONCLUSIONS: The ranking of
      Spanish cardiovascular research is similar to that of other biomedical fields,
      though its position is less favorable in relation to certain demographic and
      economical indicators. In order to maintain adequate investigational levels, it
      is necessary for the European governments and scientific societies to regard the
      promotion of high-quality cardiological research as a priority concern.

PMID- 20038408
TI  - Spanish cardiac catheterization and coronary intervention registry. 18th official
      report of the Spanish Society of Cardiology Working Group on Cardiac
      Catheterization and Interventional Cardiology (1990-2008).
AB  - INTRODUCTION AND OBJECTIVES: Each year the Spanish Society of Cardiology Working
      Group on Cardiac Catheterization and Interventional Cardiology reports on the
      data contained in a national registry of procedures performed. The present report
      is for the year 2008. It contains information on the scope of interventional
      cardiology in Spain and provides data for use in comparisons with other
      countries. METHODS: Hospitals provided data voluntarily. The information was
      analyzed by the steering committee of the Working Group. RESULTS: Data were
      submitted by 131 hospitals (74 public and 57 private) that performed relevant
      procedures, mainly in adults. In total, 136,458 diagnostic procedures were
      carried out, of which 123,031 involved coronary angiography. Numbers were little
      changed from the previous year, with an overall rate of 2658 coronary angiograms
      per million population. The number of percutaneous coronary interventions
      increased by 2.2% to 61,810, with a rate of 1334 per million inhabitants. In
      addition, 101,753 stents were implanted, of which 58.2% were drug-eluting. The
      number of procedures carried out for acute myocardial infarction was 12,079,
      which makes up 20.6% of all percutaneous coronary interventions and is an
      increase of 6.7% relative to 2007. The most common intervention in adults with
      congenital heart disease was closure of an atrial septal defect, which was
      performed in 305 cases. The most common valve procedure was mitral valvuloplasty,
      which was performed in 371 cases with a success rate of 96%. Further, 151 aortic
      percutaneous valves were implanted. CONCLUSIONS: The most significant increases
      in activity were in procedures for ST-segment elevation myocardial infarction and
      percutaneous valve implantation. The rates of all other diagnostic and
      therapeutic procedures changed only slightly.

PMID- 20038410
TI  - Spanish pacemaker registry. 6th official report of the Spanish Society of
      Cardiology Working Group on Cardiac Pacing (2008).
AB  - INTRODUCTION AND OBJECTIVES: This article describes the findings of an analysis
      of data on pacemaker implantations and replacements reported to the Spanish
      Pacemaker Registry during 2008. METHODS: The data came primarily from information
      recorded on European Pacemaker Patient Identification Cards. RESULTS: Data were
      received from 116 hospital units, which submitted a total of 11,855
      identification cards representing 36.3% of all pacemakers implanted. There was a
      marked increase in the number of pacemaker units used, which rose to a rate of
      708.3 per million inhabitants. The frequency of pacemaker implantation increased
      and the mean age of male patients decreased. The largest number of implantations
      were carried out in patients in their 70s, who comprised 39.1% of the total. The
      most frequent electrocardiographic indication was atrioventricular block. With
      regard to pacing leads, active fixation leads were used in the atrium in 59.3% of
      cases and in the ventricle in 37.9% of cases. There was an improvement in the
      choice of pacing mode, with age being a determining factor. For example, in sick
      sinus syndrome, the VVI/R mode was used in a 29% of patients aged over 80 years
      compared with 14% of those aged under 80 years. CONCLUSIONS: Age was found to be
      one factor influencing the selection of the most appropriate pacing mode. Active
      fixation leads were used more often, reaching 44.5% of leads implanted.
      Atrioventricular pacing was used in a greater percentage of cases than in any
      other time period covered by the pacemaker registry.

PMID- 20038409
TI  - Spanish implantable cardioverter-defibrillator registry. 5th official report of
      the spanish society of cardiology working group on implantable cardioverter
      defibrillators (2008).
AB  - INTRODUCTION AND OBJECTIVES: To summarize the findings of the Spanish Implantable
      Cardioverter-Defibrillator (ICD) Registry for 2008 compiled by the Spanish
      Society of Cardiology Working Group on Implantable Cardioverter-Defibrillators.
      METHODS: Prospective data recorded voluntarily on single-page questionnaires were
      sent to the Spanish Society of Cardiology by each implantation team. RESULTS:
      Overall, 3486 device implantations were reported, which is 84.7% of the estimated
      total number of implantations. The reported implantation rate was 76 per million
      population and the estimated total implantation rate was 90 per million. The
      proportion of first implantations was 78.1%. There continued to be substantial
      regional variations within Spain. The majority of ICD implantations took place in
      men (mean age 62+/-12 years) who had severe or moderate-to-severe ventricular
      dysfunction and were in New York Heart Association functional class II. Ischemic
      heart disease was the most frequent underlying cardiac condition, followed by
      dilated cardiomyopathy. The number of indications for primary prevention
      increased relative to the previous year, especially in patients with ischemic
      cardiomyopathy, and now account for 57% of first implantations. The types of ICD
      implanted were unchanged from 2007. Overall, 73.6% of ICDs were implanted by
      cardiac electrophysiologists. CONCLUSIONS: The 2008 Spanish ICD Registry includes
      data on almost 85% of all ICD implantations performed in Spain. Although the
      number has continued to increase, it still remains far from the European average.
      There was a significant increase in indications for primary prevention.
      Substantial regional variations continue to exist within Spain.

PMID- 20038415
TI  - Multimodal imaging study of a thrombosed right coronary artery aneurysm.

PMID- 20038416
TI  - Relationship between metabolic syndrome and ischemic heart disease mortality in
      Spain.
AB  - Morbidity and mortality due to ischemic heart disease (IHD) is subject to wide
      geographic variation both between and within countries. The aim of this study was
      to determine whether geographic variations exist in the prevalence of metabolic
      syndrome in the Spanish working population or in its relationship with IHD
      mortality. We analyzed clinical and laboratory data obtained during health check
      ups carried out in Spanish workers (n=17,837) during 2003. The prevalence of
      metabolic syndrome was 17% in men and 6.5% in women. However, there was a
      heterogeneous distribution across the different regions studied. The prevalence
      in southern and western regions (e.g., in men: 22.15% in Extremadura and 20.6% in
      Galicia) was double that observed in central and northern zones (e.g., in the
      Basque Country and Castile and Leon). This research indicates that there is a
      significant association between IHD mortality and the prevalence of metabolic
      syndrome in workers from different Spanish regions.

PMID- 20038417
TI  - Hypertrophic cardiomyopathy. A study of the troponin-T gene in 127 Spanish
      families.
AB  - The information available on the correlation between genotype and phenotype and
      the prognostic implications of different troponin-T gene mutations is sparse and,
      at times, contradictory. We studied the TNNT2 gene in 127 patients with
      hypertrophic cardiomyopathy and identified three mutations in patients from four
      families (3.1%): the Phe87Leu mutation, which has not been previously reported,
      the Arg278Cys mutation (two families) and the Asp271Ile mutation. Seven carriers
      of the Phe87Leu mutation (aged 29 to 52 years) were found to have mild
      hypertrophy (i.e., a wall thickness <16 mm). There were 11 deaths associated with
      the condition (seven sudden deaths), and four of those who died were aged between
      14 and 16 years. No sudden deaths occurred in the other three families. In
      conclusion, troponin-T mutations were responsible for 3% of the hypertrophic
      cardiomyopathy cases in our study population. The Phe87Leu mutation was
      associated with only mild hypertrophy but with a high risk of sudden death.

PMID- 20038418
TI  - Medium-term echocardiographic follow-up of systolic and diastolic left
      ventricular abnormalities after surgical treatment of subacute rupture.
AB  - Subacute rupture of the left ventricular free wall is a complication that occurs
      during the acute phase of a myocardial infarction. The subacute presentation
      makes surgical management possible. However, it is not known whether either
      pericardial manipulation or the use of pericardial patches influences left
      ventricular function over the medium term. Our aim was to monitor changes in left
      ventricular function and the development of constrictive pericarditis over the
      medium term in patients who had been treated surgically for subacute rupture of
      the left ventricle. Eleven patients with subacute rupture underwent surgery, of
      whom six were followed up over the medium term. A modest improvement in left
      ventricular systolic function was observed and there was no evidence of
      constrictive pericarditis. In conclusion, the surgical approach appears to be
      safe over the medium term and had no influence on left ventricular function. Nor
      did it lead to the development of constrictive pericarditis.

PMID- 20038419
TI  - Revista Espanola de Cardiologia 2009: Editorial thoughts.

PMID- 20038420
TI  - The role of European national journals in education.

PMID- 20038421
TI  - Iatrogenic tako-tsubo cardiomyopathy secondary to catecholamine administration.

PMID- 20038422
TI  - Very late stent thrombosis due to late stent malapposition.

PMID- 20038423
TI  - Right coronary artery injury as a complication of de Vega tricuspid annuloplasty.

PMID- 20038424
TI  - Implantation via the femoral vein of a biventricular defibrillator with
      transseptal endocardial left ventricular pacing.

PMID- 20038425
TI  - Heart failure in the elderly and geriatric assessment.

PMID- 20038427
TI  - Importance of determining the left ventricular ejection fraction in elderly
      patients with acute heart failure seen in emergency departments.

PMID- 20038428
TI  - Women in cardiology research in Spain look forward to equality. Reflections from
      under the glass ceiling.

PMID- 20038429
TI  - Re: Misleading comments in Ranganathan et al. "Recombinant pro-apoptotic
      Mycobacterium tuberculosis generates CD8+ T cell responses against human
      immunodeficiency virus type 1 Env and M. tuberculosis in neonatal mice".

PMID- 20038430
TI  - A summer school on vaccinology: Responding to identified gaps in pre-service
      immunisation training of future health care workers.
AB  - Immunisation is one of the corner stones of public health. Most health care
      consumers see the health care worker as their major source of information on
      immunisation and vaccine safety. Doctors, nurses and midwives should be
      appropriately and timely trained for that role. Within the Vaccine Safety,
      Attitudes, Training and Communication (VACSATC) EU-project a specific work
      package focused on the possible improvements of pre-service training of future
      health care workers. Surveys to assess current pre-service training about
      knowledge, skills and competences towards immunisation were distributed to
      students and curriculum managers of medical schools, universities and nursing
      training institutions in seven EU countries. In all responding institutions
      training on vaccines and immunisation is disseminated over a wide range of
      courses over several academic years. Topics as immunology and vaccine-preventable
      diseases are well covered during the pre-service training but major gaps in
      knowledge and competences were identified towards vaccine safety, communication
      with parents, addressing anti-vaccine arguments and practical skills. This
      assessment underlined the rationale for adequate pre-service training and
      identified opportunities for improvement of pre-service training. A prototype of
      an accurate pre-service immunisation curriculum was developed, implemented and
      evaluated in the summer of 2009 with a group of 36 students from 19 countries
      during a summer school on vaccinology at the Antwerp University, Belgium.

PMID- 20038431
TI  - A beta-glucan-conjugate vaccine and anti-beta-glucan antibodies are effective
      against murine vaginal candidiasis as assessed by a novel in vivo imaging
      technique.
AB  - The protective capacity of a parenterally administered beta-glucan-conjugate
      vaccine formulated with the human-compatible MF59 adjuvant was assessed in a
      murine model of vaginal candidiasis. To monitor infection, an in vivo imaging
      technique exploiting genetically engineered, luminescent Candida albicans was
      adopted, and compared with measurements of colony forming units. The vaccine
      conferred significant protection, and this was associated with production of
      serum and vaginal anti-beta-glucan IgG antibodies. Vaginal IgG molecules were the
      likely mediators of protection as inferred by the efficacy of passive transfer of
      immune vaginal fluid and passive protection by an anti-beta-1,3-glucan mAb.
      Overall, the in vivo imaging technique was more reliable than vaginal CFU counts
      in assessing the extent and duration of the vaginal infection, and the consequent
      protection level.

PMID- 20038432
TI  - Betacellulin protects from pancreatitis by activating stress-activated protein
      kinase.
AB  - BACKGROUND & AIMS: Acute pancreatitis (AP) is a serious, unpredictable clinical
      problem, the pathophysiology of which is poorly understood. Here, we evaluate
      whether betacellulin (BTC), a ligand of the epidermal growth factor receptor also
      able to activate the proapoptotic ERBB4 receptor, can protect against
      experimental AP. METHODS: AP was induced in transgenic mice overexpressing BTC
      (BTC-tg), control mice, or control mice after administration of recombinant BTC.
      The severity of pancreatitis was assessed by measurements of serum amylase and
      lipase and histologic grading. The involvement of the stress-activated protein
      kinase (SAPK) was evaluated by treating BTC-tg mice with an SAPK inhibitor before
      induction of AP. RESULTS: BTC-tg mice showed increased apoptosis and
      proliferation in the exocrine pancreas, indicating an increased cell turnover.
      There was a marked, epidermal growth factor receptor-independent decrease in
      pancreas weight. After induction of AP by cerulein injection, BTC-tg mice showed
      a significantly lower increase in serum amylase and lipase levels as well as less
      pronounced tissue necrosis, edema, and inflammation, as compared to nontransgenic
      littermates. This protective effect, also confirmed in the L-arginine AP model,
      was associated with increased phosphorylation of SAPK and abrogated after
      treatment of BTC-tg mice with a SAPK inhibitor. Finally, the protective effect of
      BTC against AP was confirmed by treating nontransgenic mice with recombinant BTC.
      CONCLUSIONS: These findings indicate a potential application of the BTC/ERBB4
      pathway for modulating the course of AP.

PMID- 20038433
TI  - Functional switching of TGF-beta1 signaling in liver cancer via epigenetic
      modulation of a single CpG site in TTP promoter.
AB  - BACKGROUND & AIMS: Acquisition of resistance to the antiproliferative effect of
      transforming growth factor (TGF)-beta1 is crucial for the malignant progression
      of cancers. In this study, we sought to determine whether deregulated expression
      of tristetrapolin (TTP), a negative posttranscriptional regulator of c-Myc,
      confers resistance to the antiproliferative effects of TGF-beta1 on liver cancer
      cells. METHODS: The epigenetics of TTP promoter regulation and its effects on TGF
      beta1 signaling were examined in hepatocellular carcinoma (HCC) cell lines and
      patient tissues. RESULTS: TTP was down-regulated in HCC cell lines (10/11),
      compared with normal liver, as well as in tumor tissues (19/24) from paired HCC
      specimens. Methylation of a specific single CpG site located within the TGF-beta1
      responsive region (TRR) of the TTP promoter was significantly associated with TTP
      down-regulation in both HCC cell lines and tumor tissues (r = -0.606383, P <
      .001). The singly methylated CpG site was specifically bound by a transcriptional
      repressor complex consisting of MECP2/c-Ski/DNMT3A and abolished the TGF-beta1
      induced as well as basal-level expression of TTP. The epigenetic inactivation of
      TTP led to an increased half-life of c-Myc mRNA and blocked the cytostatic effect
      of TGF-beta1. Statistically significant correlations were observed between the
      single CpG site methylation and expression levels of TTP or c-Myc in clinical
      samples of HCC. CONCLUSIONS: Abrogation of the post-transcriptional regulation of
      c-Myc via methylation of a specific single CpG site in the TTP promoter presents
      a novel mechanism for the gain of selective resistance to the antiproliferative
      signaling of TGF-beta1 in HCC.

PMID- 20038434
TI  - The functional organisation of the fronto-temporal language system: evidence from
      syntactic and semantic ambiguity.
AB  - Spoken language comprehension is known to involve a large left-dominant network
      of fronto-temporal brain regions, but there is still little consensus about how
      the syntactic and semantic aspects of language are processed within this network.
      In an fMRI study, volunteers heard spoken sentences that contained either
      syntactic or semantic ambiguities as well as carefully matched low-ambiguity
      sentences. Results showed ambiguity-related responses in the posterior left
      inferior frontal gyrus (pLIFG) and posterior left middle temporal regions. The
      pLIFG activations were present for both syntactic and semantic ambiguities
      suggesting that this region is not specialised for processing either semantic or
      syntactic information, but instead performs cognitive operations that are
      required to resolve different types of ambiguity irrespective of their linguistic
      nature, for example by selecting between possible interpretations or
      reinterpreting misparsed sentences. Syntactic ambiguities also produced
      activation in the posterior middle temporal gyrus. These data confirm the
      functional relationship between these two brain regions and their importance in
      constructing grammatical representations of spoken language.

PMID- 20038435
TI  - From numbers to letters: feedback regularization in visual word recognition.
AB  - Word reading in alphabetic languages involves letter identification,
      independently of the format in which these letters are written. This process of
      letter 'regularization' is sensitive to word context, leading to the recognition
      of a word even when numbers that resemble letters are inserted among other real
      letters (e.g., M4TERI4L). The present study investigates the electrophysiological
      correlates of number-to-letter regularization by means of the masked priming
      paradigm: target words (MATERIAL) were preceded by fully alphabetic primes
      (MATERIAL), primes with letter-like numbers (M4T3R14L), or primes with unrelated
      numbers (M7T6R28L). ERPs revealed three subsequent effects. Around 150 ms the
      unrelated numbers condition elicited a positive effect, compared to the other two
      conditions, in the occipital electrodes. Then, target words preceded by primes
      with numbers elicited a more negative N200 in the same electrodes compared to the
      fully alphabetic condition. Finally, both alphabetic primes and letter-like
      numbers elicited a posterior positive component peaking around 260 ms compared to
      unrelated numbers. Source analysis for each electrophysiological effect revealed
      a similar early increase of activity in the left occipito-temporal pathway for
      alphabetic primes and primes with letter-like numbers. Around 200 ms, the
      orthographic interference due to the numerical values correlated with an increase
      of activity in parietal areas; finally, a recursive effect in the left occipital
      cortex was found, reflecting abstract letter activation. These results indicate
      that direct feedback interaction from word units strongly influences the
      activation of the letter units at a format-independent abstract level.

PMID- 20038436
TI  - Amodal semantic representations depend on both anterior temporal lobes: evidence
      from repetitive transcranial magnetic stimulation.
AB  - The key question of how the brain codes the meaning of words and pictures is the
      focus of vigorous debate. Is there a "semantic hub" in the temporal poles where
      these different inputs converge to form amodal conceptual representations?
      Alternatively, are there distinct neural circuits that underpin our comprehension
      of pictures and words? Understanding words might be primarily left-lateralised,
      linked to other language areas, while semantic representation of pictures may be
      more bilateral. To elucidate this debate, we used offline, low-frequency,
      repetitive transcranial magnetic stimulation (rTMS) to disrupt neural processing
      temporarily in the left or right temporal poles. During the induced refractory
      period, participants made judgements of semantic association for verbal and
      pictorial stimuli. The efficiency of semantic processing was reduced by rTMS, yet
      a perceptual task of comparable difficulty was unaffected. rTMS applied to the
      left or right temporal poles disrupted semantic processing for words and pictures
      to the same degree, while rTMS delivered at a control site had no impact. The
      results confirm that both temporal poles form a critical substrate within the
      neural network that supports conceptual knowledge, regardless of modality.

PMID- 20038437
TI  - Validation of suitable internal control genes for expression studies in aging.
AB  - Quantitative data from experiments of gene expression are often normalized
      through levels of housekeeping genes transcription by assuming that expression of
      these genes is highly uniform. This practice is being questioned as it becomes
      increasingly clear that the level of housekeeping genes expression may vary
      considerably in certain biological samples. To date, the validation of reference
      genes in aging has received little attention and suitable reference genes have
      not yet been defined. Our aim was to evaluate the expression stability of
      frequently used reference genes in human peripheral blood mononuclear cells with
      respect to aging. Using quantitative RT-PCR, we carried out an extensive
      evaluation of five housekeeping genes, i.e. 18s rRNA, ACTB, GAPDH, HPRT1 and
      GUSB, for stability of expression in samples from donors in the age range 35-74
      years. The consistency in the expression stability was quantified on the basis of
      the coefficient of variation and two algorithms termed geNorm and NormFinder. Our
      results indicated GUSB be the most suitable transcript and 18s the least for
      accurate normalization in PBMCs. We also demonstrated that aging is a confounding
      factor with respect to stability of 18s, HPRT1 and ACTB expression, which were
      particularly prone to variability in aged donors.

PMID- 20038438
TI  - Presynaptic effects of grayanotoxin III on excitatory and inhibitory nerve
      terminals in rat ventromedial hypothalamic neurons.
AB  - Mad honey poisoning caused by grayanotoxin (GTX) is associated with autonomic
      nervous system symptoms, such as excessive perspiration, hypersalivation,
      vomiting, and bradycardia. Neurons in the ventromedial hypothalamus (VMH) play an
      important role in body homeostasis and in the activity of the autonomic nervous
      system. Among the 18 isoforms of GTX found in mad honey, GTX I-IV are a unique
      class of toxic diterpenoids; GTX III is the principal toxic isomer. In the
      present study, we determined the effects of GTX III on synaptic transmission in
      VMH neurons. Both spontaneous and evoked GABA-ergic and glutamate-ergic
      postsynaptic currents were measured using patch clamp recordings in single VMH
      neurons which had been mechanically dissociated. GTX III increased the frequency
      of spontaneous GABA-ergic and glutamate-ergic postsynaptic currents (sIPSCs and
      sEPSCs, respectively) in a dose-dependent manner without affecting their
      amplitude, demonstrating that GTX III enhances transmitter release from both
      inhibitory and excitatory nerve terminals synapsing onto VMH neurons. GTX III
      significantly enhanced the amplitude and the success rate (Rsuc) of both evoked
      inhibitory and excitatory postsynaptic currents (eIPSCs and eEPSCs,
      respectively), suggesting that GTX III increases the probability of transmitter
      release from these terminals, and also the amount of transmitter released from a
      single nerve terminal. The action of GTX III on sIPSC frequency was absent in a
      Na(+)-free solution and in the presence of tetrodotoxin (TTX; 300 nM) or cadmium
      (Cd(2+); 100 microM). The present study indicates that GTX increases Ca(2+)
      influx through voltage-dependent Ca(2+) channels secondary to activation of
      voltage-dependent Na(+) channels in inhibitory and excitatory nerve terminals
      synapsing on VMH neurons, and the subsequent increased release of GABA and
      glutamate from these terminals may be responsible for the autonomic symptoms of
      GTX intoxication.

PMID- 20038439
TI  - Identification and clinical association of anti-cytokeratin 18 autoantibody in
      COPD.
AB  - The etiology of chronic obstructive pulmonary disease (COPD) remains unclear. A
      mechanism involving the autoimmune reaction in the pathogenesis of COPD has been
      proposed but not confirmed. The aim of this study was to investigate whether
      serum autoantibodies against pulmonary cellular proteins are present in COPD
      patients and to identify their autoantigens if possible. Samples from 50 COPD
      patients and 42 control subjects were studied. Circulating autoantibodies were
      detected by Western blot. Immunoprecipitation and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to
      identify the autoantigens. Autoantibodies against pulmonary cellular antigens
      were found in the sera of COPD patients. Specifically, an autoantibody against
      the 45-kDa human cytokeratin 18 protein was found in 76.0% of COPD patients and
      23.8% of control subjects (p<0.001). Furthermore, the cytokeratin 18 autoantibody
      level was positively correlated with the FEV(1) (L) (p=0.013) and FEV(1) (%pred.)
      (p=0.043) values observed in COPD patients. This study identified the pulmonary
      epithelial cytokeratin 18 protein as a COPD-associated autoantigen and found that
      anti-cytokeratin 18 autoantibodies were prevalent in COPD patients. Our results
      support the hypothesis that humoral autoimmunity may be involved in the
      pathogenesis of COPD.

PMID- 20038440
TI  - Smoking status interacts with the association between mannose-binding lectin
      serum levels and gene polymorphism and the carriage of oropharyngeal bacteria.
AB  - Mannose-binding lectin (MBL) role in the carriage of oropharyngeal bacteria is
      not known. We investigated the association of smoking, MBL2 polymorphisms, and
      MBL concentrations with oropharyngeal carriage of respiratory bacteria in young
      men. Oropharyngeal specimens, MBL concentrations, and MBL2 gene polymorphisms
      were measured in 124 asthmatic and 394 nonasthmatic Finnish military recruits.
      The carriage rates of S. pneumoniae (p = 0.002), N. meningitidis (p = 0.005), and
      beta-hemolytic streptococci (p < 0.001) throughout the military service were
      significantly higher among smokers than in nonsmokers. An MBL level below the
      median proved to be a significant risk factor for the carriage of N. meningitidis
      (odds ratio [OR] = 1.9; 95% confidence interval [CI] 1.0-3.6) and beta-hemolytic
      streptococci (OR = 2.0; 95% CI 1.2-3.2) in the nonsmokers and a borderline
      significant risk factor for the carriage of S. pneumoniae (OR = 1.5; 95% CI 0.9
      2.6), whereas low MBL levels producing MBL2 haplotypes (LXA/LXA, LXA/O, HYA/O,
      LYA/O, O/O) seemed to be associated with the carriage of N. meningitidis (OR =
      1.8; 95% CI 1.0-3.4) and S. pneumoniae (OR = 1.6; 95% CI 0.9-2.7). Thus, MBL
      deficiency may predispose nonsmokers to oropharyngeal carriage of these bacteria.
      We hypothesize that the major factor contributing to elevated bacterial carriage
      in smokers might be increased bacterial adherence to epithelial cells, which
      obscures the effect of MBL.

PMID- 20038441
TI  - Single-trial electroencephalogram predicts cardiac acceleration: a time-lagged P
      correlation approach for studying neurovisceral connectivity.
AB  - Cortical efferences to the heart are important for cardiovascular health,
      psychopathology, emotion regulation and other dimensions of human functioning.
      Although researchers have already begun to outline the underlying neuroanatomy,
      the timing of neurovisceral communication in humans is difficult to study non
      invasively. A possible coupling between the brain and the heart can be observed
      following feedback stimuli, which have been shown to evoke both, early (i.e. <500
      ms) signatures in the electroencephalogram (EEG) and changes in the chronotropy
      of subsequent heart beats. Because standard approaches may be insufficient to
      study how these responses are related, we suggest a method termed "Cardio
      Electroencephalographic Covariance Tracing" (CECT), which is based on time-lagged
      P-correlations (i.e., correlations within individuals) between single-trial EEG
      magnitudes and heart period changes. When CECT was applied to data from n=31
      individuals who performed a gambling task, central midline EEG magnitudes from
      280 to 340 ms after feedback reliably P-correlated with cardiac acceleration 2 to
      5 s thereafter. In addition positive vs. negative feedback lead to enhanced event
      related potential amplitudes from 200 to 280 ms and to relative cardiac
      acceleration from 1 to 3.5 s after feedback presentation. The results imply that
      neurogenic cardiac modulations begin to be affected 200 to 400 ms after stimulus
      presentation and demonstrate the utility of CECTs for future investigations.

PMID- 20038442
TI  - Sensitization of the transient receptor potential vanilloid type 1 ion channel by
      isoflurane or sevoflurane does not result in extracellular signal-regulated
      kinase 1/2 activation in rat spinal dorsal horn neurons.
AB  - Clinically relevant concentrations of isoflurane or sevoflurane sensitize
      transient receptor potential vanilloid type 1 to several of its activators,
      including capsaicin. It has, moreover, been suggested these volatile general
      anaesthetics may augment nociceptive signalling arising from surgical procedures
      and thereby contribute to post-operative pain. To investigate this suggestion, we
      have studied intraplantar capsaicin injection-induced phosphorylation of
      extracellular signal-regulated kinase 1/2 in spinal dorsal horn neurons (which is
      a recognized marker of spinal nociceptive processing) in rat during isoflurane or
      sevoflurane anaesthesia after 60 min under anaesthesia. Control animals were
      anaesthetized with pentobarbital (which of itself does not activate extracellular
      signal-regulated kinase 1/2 in spinal dorsal horn neurons). Unilateral
      intraplantar capsaicin injection in control animals evoked extracellular signal
      regulated kinase 1/2 phosphorylation in a group of neurons in lamina I and lamina
      II of the ipsilateral spinal dorsal horn in a somatotopically appropriate area.
      In contrast, both anaesthetic gases (given for 60 min and without subsequent
      capsaicin injection) induced extracellular signal-regulated kinase 1/2 activation
      in a different group of mainly lamina I neurons bilaterally. The total number of
      spinal dorsal horn neurons labelled on the ipliateral side following capsaicin
      injection into the isoflurane-, or sevoflurane-, anaesthetized animals was
      significantly less than that produced by capsaicin alone. Further, capsaicin
      injection into isoflurane-, or sevoflurane-, anaesthetized animals reduced
      extracellular signal-regulated kinase 1/2 phosphorylation induced by the gases
      alone on both sides. These findings do not support the suggestion that isoflurane
      , or sevoflurane-, induced sensitization of transient receptor potential
      vanilloid type 1 by capsaicin, or other agonist, is translated into induction of
      spinal nociceptive processing and consequential pain sensation.

PMID- 20038443
TI  - Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a
      threonine-serine protein kinase B-dependent mechanism.
AB  - Bupivacaine is one of the amide type local anesthetics and is widely used for
      epidural anesthesia and blockade of nerves. Bupivacaine administration locally
      could result in neuron injury showing transient neurologic symptoms.
      Dexamethasone is a synthetic glucocorticoid and may exert cytoprotective
      properties against damage induced by some stimuli. In the present study, we
      evaluated the effects of dexamethasone on bupivacaine-induced toxicity in mouse
      neuroblastoma N2a cells. N2a cells were exposed to bupivacaine in the presence or
      absence of dexamethasone. After treatment, the cell viability, nuclear
      condensation, and lactate dehydrogenase levels were evaluated. Mitochondrial
      potential and Akt (threonine-serine protein kinase B) activation were also
      examined. In a separate experiment, we examined the effect of Akt inhibition by
      triciribine on cell viability following dexamethasone treatment. We also
      investigated whether dexamethasone could prevent lidocaine-induced neurotoxicity.
      Treatment of N2a cells with bupivacaine resulted in significant cell injury as
      evidenced by morphological changes, LDH leakage, and nuclear condensation.
      Pretreatment of the cells with dexamethasone significantly attenuated bupivacaine
      and lidocaine-induced cell injury. Dexamethasone treatment prevented the decline
      of mitochondrial potential caused by bupivacaine and increased the levels of Akt
      phosphorylation. Importantly, pharmacological inhibition of Akt abolished the
      protective effect of dexamethasone against bupivacaine-induced cell injury. Our
      data suggest that pretreatment of neuroblastoma cells with dexamethasone exerts a
      protective effect on bupivacaine-induced neuronal cell injury. The mechanisms
      involve activating the Akt signaling pathway.

PMID- 20038445
TI  - Plasticity changes of neuronal activities in central lateral nucleus by
      stimulation of the anterior cingulate cortex in rat.
AB  - The medial thalamus (MT) and anterior cingulate cortex (ACC) are essential
      components in mediating the affective emotional-aspect of pain. Whether ACC
      modulates the neuron activity in MT has not been elucidated and clarifying this
      point will further reveal the neurobiological mechanism underlying pain related
      emotions. In the present study, we used in vivo single unit recording and
      retrograde tracing technique to demonstrate that the majority of examined neurons
      in the central lateral nucleus (CL), an important nucleus of MT, responded to
      noxious stimulation. Tetanic stimulation in the ACC increased spike activities of
      nociceptive-responding neurons in the CL; retrograde tracing by fluorogold in the
      CL showed the positive neurons are distributed bilaterally in the ACC. Taken
      together, we demonstrated descending modulation to nociceptive responses of CL
      neurons by direct projections from the ACC, which may underlie the neuronal
      mechanism of negative pain emotions.

PMID- 20038444
TI  - Forebrain projections of arcuate neurokinin B neurons demonstrated by anterograde
      tract-tracing and monosodium glutamate lesions in the rat.
AB  - Neurokinin B (NKB) and kisspeptin receptor signaling are essential components of
      the reproductive axis. A population of neurons resides within the arcuate nucleus
      of the rat that expresses NKB, kisspeptin, dynorphin, NK3 receptors and estrogen
      receptor alpha (ERalpha). Here we investigate the projections of these neurons
      using NKB-immunocytochemistry as a marker. First, the loss of NKB-immunoreactive
      (ir) somata and fibers was characterized after ablation of the arcuate nucleus by
      neonatal injections of monosodium glutamate. Second, biotinylated dextran amine
      was injected into the arcuate nucleus and anterogradely labeled NKB-ir fibers
      were identified using dual-labeled immunofluorescence. Four major projection
      pathways are described: (1) local projections within the arcuate nucleus
      bilaterally, (2) projections to the median eminence including the lateral
      palisade zone, (3) projections to a periventricular pathway extending rostrally
      to multiple hypothalamic nuclei, the septal region and BNST and dorsally to the
      dorsomedial nucleus and (4) Projections to a ventral hypothalamic tract to the
      lateral hypothalamus and medial forebrain bundle. The diverse projections provide
      evidence that NKB/kisspeptin/dynorphin neurons could integrate the reproductive
      axis with multiple homeostatic, behavioral and neuroendocrine processes.
      Interestingly, anterograde tract-tracing revealed NKB-ir axons originating from
      arcuate neurons terminating on other NKB-ir somata within the arcuate nucleus.
      Combined with previous studies, these experiments reveal a bilateral
      interconnected network of sex-steroid responsive neurons in the arcuate nucleus
      of the rat that express NKB, kisspeptin, dynorphin, NK3 receptors and ERalpha and
      project to GnRH terminals in the median eminence. This circuitry provides a
      mechanism for bilateral synchronization of arcuate NKB/kisspeptin/dynorphin
      neurons to modulate the pulsatile secretion of GnRH.

PMID- 20038446
TI  - Understanding the quality of protein loaded PLGA nanoparticles variability by
      Plackett-Burman design.
AB  - The aim of this investigation was to screen and understand the product
      variability due to important factors affecting the characteristics CyA-PLGA
      nanoparticles prepared by O/W emulsification-solvent evaporation method.
      Independent variables studied were cyclosporine A (CyA) (X(1)), PLGA (X(2)), and
      emulsifier concentration namely SLS (X(3)), stirring rate (X(4)), type of organic
      solvent employed (chloroform or dichloromethane, X(5)) and organic to aqueous
      phase ratio (X(6)). The nanoparticles properties considered were encapsulation
      efficiency (Y(1)), mean particle size (Y(2)), zeta potential (Y(3)), burst effect
      (Y(4)) and dissolution efficiency (Y(5)). The statistical analysis of the results
      allowed determining the most influent factors. The nanoparticles were
      characterized by scanning electron microscopy (SEM), differential scanning
      calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared
      (FTIR) spectroscopy. The factors combination showed variability of entrapment
      efficiency (Y(1)), mean particle size (Y(2)) and zeta potential (Y(3)) from
      10.17% to 93.01%, 41.60 to 372.80 nm and 29.60 to 34.90 mV, respectively.
      Initially, nanoparticles showed burst effect followed by sustained release during
      the 7-day in vitro release study period. The dissolution efficiency (Y(5)) varied
      from 52.67% to 84.11%. The nanoparticles revealed Higuchi release pattern and
      release occurred by coupling of diffusion and erosion. In conclusion, this study
      revealed the potential of QbD in understanding the effect of formulation and
      process variables on the characteristics on CyA-PLGA nanoparticles.

PMID- 20038447
TI  - Influence of fines on the surface energy heterogeneity of lactose for pulmonary
      drug delivery.
AB  - The effects of the blending of lactose fines to the overall adhesion property of
      coarse alpha-lactose monohydrate carrier particles were investigated. Five
      samples, three of them commercial samples from DOMO (Lactohale) LH100, LH210, and
      LH250) whilst the other two are blends of LH210 and LH250, were studied.
      Characterisation included particle sizing, SEM, PXRD and IGC. Dispersive surface
      energy gamma(SV)(d) was determined using a finite concentration IGC method to
      obtain a distribution profile. The gamma(SV)(d) distribution of lactose crystals
      was found to vary from 40 to 48mJ/m(2). The unmilled coarse crystalline lactose
      sample (LH100) gamma(SV)(d) was lowest and showed less heterogeneity than the
      milled sample (LH250). Fines (LH210) were found to have the highest gamma(SV)(d)
      value. The samples with loaded LH210 were found to have a higher energy than
      LH100. The amount of LH210 in Blend 1 was not able to decrease surface energy
      heterogeneity, whereas sample Blend 2 showed adequate loading of fines to obtain
      a relatively homogeneous surface. Addition of fines resulted in an increase in
      gamma(SV)(d), suggesting that coarse lactose surfaces were replaced by surfaces
      of the fines. Increasing the loading of fines may result in a more homogeneous
      surface energy of lactose particles.

PMID- 20038448
TI  - Modelling of porosity and waterfronts in cellulosic pellets for understanding
      drug release behavior.
AB  - The microstructure of cellulose microcrystalline-Carbopol pellets, prepared under
      different drying conditions (oven-dried or freeze-dried), was experimentally
      characterized using mercury intrusion porosimetry and then computationally
      modelled using Pore-Cor software. Connectivity (mean number of throats per pore),
      pore skew (sigma), throat skew (q) and correlation level were estimated and
      simultaneously optimized from the mercury intrusion porosimetry cumulative curves
      using the Boltzmann-annealed simplex algorithm. Unit cells with percolation
      properties close to the real ones were generated. Water penetration rate in the
      simulated structures was also modelled using Pore-Cor and the waterfront position
      was calculated using the Bosanquet equation. A close correlation was found
      between the simulated water flow rate in the unit cell and the experimental
      theophylline first-order release rate constant. Thus, modelling of network
      microstructure and waterfronts appears as an useful tool for predicting drug
      release rate from matrix pellets.

PMID- 20038449
TI  - Evaluation of behavioral and pharmacological effects of Hedyosmum brasiliense and
      isolated sesquiterpene lactones in rodents.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hedyosmum brasiliense Miq. (Chloranthaceae) is an
      essential Brazilian species largely found in the Atlantic Forest. It is popularly
      known as "cidrao" and in folk medicine, this aromatic species is widely used as a
      calmative/tranquilizer and to treat sleep disorders. AIM OF THE STUDY: To examine
      the neurochemical properties of ethanol extract (EEHb), fractions and compounds
      of fresh leaves of Hedyosmum brasiliense and the antidepressant effect of the
      isolated sesquiterpene lactones podoandin and 13-hydroxy-8,9
      dehydroshizukanolide. MATERIALS, METHODS AND RESULTS: The effects of EEHb were
      demonstrated by the open field, elevated-plus-maze, forced swimming,
      pentobarbital-induced sleeping time, PTZ-induced seizure, and inhibitory
      avoidance tests. EEHb did not show a protective effect against PTZ-induced
      convulsions. In the plus-maze test, EEHb (100mg/kg, i.p.) exhibited an anxiolytic
      effect through the effective enhancement of the frequency and time spent in the
      open arms of the maze. Conversely, the time spent and the number of entrances to
      the closed arms were decreased. All these effects were also completely reversed
      by pre-treatment with flumazenil (2.5mg/kg, i.p./a benzodiazepine receptor
      agonist), similar to the results observed with diazepam used as a positive
      standard. In this test, the anxiolytic effect of EEHb was also totally blocked by
      pre-treatment with reserpine (2.0mg/kg, i.p.), a drug known to induce depletion
      of biogenic amines. In the forced swimming test, the treatment of EEHb (100mg/kg,
      i.p. or 100mg/kg, p.o.) given in acute and chronic form (10, 50 and 100mg/kg),
      produced a decrease in immobility time, similar to that of imipramine (10mg/kg,
      i.p.), the positive control. The dichloromethane and hexane fractions (100mg/kg,
      p.o.) also produced a decrease in immobility time. In addition, the two isolated
      compounds tested in a single dose (10mg/kg, i.p.), the antidepressant effect was
      observed only with the compound podoandin, which also caused a decrease in
      immobility time. EEHb (10-100mg/kg) a dose-dependent manner also caused a
      decrease in barbiturate sleeping time in mice, and in high doses (100mg/kg), did
      not interfere in memory consolidation. CONCLUSIONS: The results suggest that EEHb
      presents psychopharmacological activities, including anxiolytic, antidepressant,
      and hypnotic effects.

PMID- 20038450
TI  - Delayed ossification in Wistar rats induced by Morinda citrifolia L. exposure
      during pregnancy.
AB  - Different products of plant Morinda citrifolia L. (noni) have been marketed and
      used around the world based on properties described by Polynesian people that use
      them for more than 2000 years. Marketing of these products is based on their
      presumptive phytotherapic properties. However there is little scientific evidence
      about their safety, especially when used during pregnancy. AIM OF THE STUDY:
      Evaluate the possible developmental toxicity of the noni fruit aqueous extract
      and commercial product of TAHITIAN NONI juice in rats exposed during pregnancy.
      MATERIALS AND METHODS: Pregnant Wistar rats were exposed by gavage to 7, 30 and
      300 mg/kg bw (body weight) of noni aqueous extract or to 0.4, 2 and 20 mL/kg bw
      (body weight) of noni juice between day 7 and day 15 of pregnancy. Caesarean
      sections were performed on day 20 of pregnancy and reproductive parameters were
      evaluated. Implantations sites and postimplantation losses were recorded. Fetuses
      were weighted and examined for externally visible anomalies. After, the fetuses
      were cleared with KOH and the bones stained with alizarin red. Skeletal
      alterations of the skull, vertebral column, ribs, forelimbs, hindlimbs, sternum,
      sings of delayed ossification and variations were examined in accordance with pre
      defined criteria and identified using harmonized and internationally accepted
      nomenclature recommended by the International Federation of Teratology Societies.
      RESULTS: Exposure with extract and juice of Morinda citrifolia did not induce
      maternal toxicity at the tested doses, but induced delayed ossification in
      fetuses. CONCLUSION: The exposure of pregnant rats to aqueous extract or juice
      Morinda citrifolia during organogenesis period may induce adverse effects on the
      normal development of fetuses. These findings indicate the need for further
      studies with noni derivates preceding their use in pregnant women.

PMID- 20038451
TI  - Isolation and characterization of a novel antihyperglycemic protein from the
      fruits of Momordica cymbalaria.
AB  - AIM OF THE STUDY: A new antihyperglycemic protein was identified in the aqueous
      extract of fruits of Momordica cymbalaria by bioassay-guided fractionation. The
      study was aimed at isolation and characterization of this protein. MATERIALS AND
      METHODS: The active principle was purified to homogeneity by ammonium sulphate
      precipitation, gel filtration column chromatography on Sephadex G-50 followed by
      reverse phase HPLC. Its N-terminal amino acid sequence was identified and
      compared in the protein data bank. Optimum dose and route of administration of
      the active principle was determined in STZ induced diabetic rats. RESULTS: A
      17kDa protein with an isoelectric point of 5.0 was identified as the active
      principle of antidiabetic action present in the aqueous extract of fruits of MC.
      It is named as M.Cy protein and found to be a novel protein by comparing its N
      terminal amino acid sequence with those in the protein data bank. It did not
      produce any hypoglycemia in either normal or diabetic rats. CONCLUSIONS: The
      results suggest that 'M.Cy protein', present in the fruits of Momordica
      cymbalaria is an effective antihyperglycemic active principle in STZ induced
      diabetic rats at a dose of 2.5mg/kg b.w.

PMID- 20038452
TI  - Bioactivity guided evaluation of anti-inflammatory and antinociceptive activities
      of Arceuthobium oxycedri (D.C.) M. Bieb.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Arceuthobium oxycedri (D.C.) M. Bieb.
      (Loranthaceae) or dwarf mistletoe is a rare semi-parasitic plant that lives on
      the branches of Juniperus oxycedrus as the host plant. In Turkish folk medicine,
      the plant is prescribed as a panacea for every kind of diseases, including,
      against infectious and inflammatory disorders of upper respiratory system and
      gastro-intestinal complaints or as a hypotensive remedy. AIM OF THE STUDY: In the
      current study, in vivo anti-inflammatory and antinociceptive effects of
      Arceuthobium oxycedri have been investigated. MATERIAL AND METHODS: The crude
      ethanolic extract of the whole plant was sequentially fractionated into five
      subextracts; explicitly, n-hexane, chloroform, ethyl acetate (EtOAc), n-butanol,
      and remaining water extracts. Further studies were carried out on the most active
      subextract, i.e. the EtOAc subextract, was further subjected to fractionation
      through successive column chromatographic applications on Silica gel 60, Sephadex
      LH-20 and LiChropep RP-18. For the activity assessment, each extract or fraction
      was submitted to bioassay systems; carrageenan-induced hind paw edema model for
      anti-inflammatory activity and p-benzoquinone induced abdominal contraction test
      for antinociceptive activity assessment. RESULTS: Among the extracts obtained,
      the ethanolic extract, EtOAc and n-butanol subextracts showed significant
      inhibitory activity in the bioassay systems. From the EtOAc subextract, a major
      component was isolated and its structure was determined as (+)-catechin by means
      of spectral techniques. CONCLUSION: Present study confirms the claimed
      utilization of the plant against inflammatory complaints in Turkish folk
      medicine.

PMID- 20038453
TI  - Novel crystalline solid dispersion of tranilast with high photostability and
      improved oral bioavailability.
AB  - Tranilast (TL) is an anti-allergic agent and widely used in the clinical
      treatment of bronchial asthma, atopic rhinitis, atopic dermatitis and keloids.
      However, therapeutic potential of TL could be partly limited because of its poor
      solubility, bioavailability, and photostability. To overcome these drawbacks,
      crystalline solid dispersion of TL (CSD/TL) was prepared by wet-milling technique
      with aim of improving physicochemical and pharmacokinetic properties.
      Physicochemical properties of the formulations prepared were characterized by
      laser diffraction and dynamic light scattering for particle size analysis,
      scanning electron microscope for morphological analysis, and powder X-ray
      diffraction and differential scanning calorimetry for crystallinity assessment.
      TL particles in CSD/TL appeared to be crystalline with diameter of 122 nm, and
      CSD/TL exhibited marked improvement in the dissolution behavior as compared to
      crystalline TL. Under irradiation of UVA/B (250 W/m(2)), solution and amorphous
      solid dispersion of TL were found to be highly photodegradable, whereas high
      photochemical stability was seen in CSD/TL. After oral administration of CSD/TL,
      enhanced TL exposure was observed with increase of C(max) and AUC by 60- and 32
      fold, respectively, as compared to crystalline TL. According to these
      observations, taken together with dissolution and pharmacokinetic behaviors,
      crystalline solid dispersion strategy would be efficacious to enhance
      bioavailability of TL with high photochemical stability.

PMID- 20038454
TI  - Isotopic biomarker discovery and application in translational medicine.
AB  - Rational drug discovery relies on pathognomonic molecular reporters of disease or
      biomarkers. Therefore biomarkers contain relational or contextual information
      about disease pathophysiology. Two broad pathways can be taken to identify
      biomarkers: a 'top-down', holistic approach that makes no assumptions about
      biomarker type, or the 'bottom-up' approach, which is hypothesis driven and
      relies on a priori information. Both approaches involve parallel or sequential
      methods that include genomic and proteomic profiling. Biomarker discovery and
      translational medicine owe much to isotopic techniques because these provide near
      real-time information about disease status as diagnostics, in drug delivery and
      for monitoring treatment. Here, we provide an overview of recent developments and
      some insight into the future role of isotopes in biomarker discovery and disease
      therapy.

PMID- 20038455
TI  - Astaxanthin intervention ameliorates cyclophosphamide-induced oxidative stress,
      DNA damage and early hepatocarcinogenesis in rat: role of Nrf2, p53, p38 and
      phase-II enzymes.
AB  - Cyclophosphamide, an alkylating agent, disturbs the oxidant and antioxidant
      balance that is associated with several unwanted toxic effects and induction of
      secondary cancers. Astaxanthin is a powerful antioxidant and possess several
      beneficial effects against various human diseases and physiological disorders.
      The present study was aimed to investigate the effects of astaxanthin against
      cyclophosphamide-induced oxidative stress, DNA damage, cell death and induction
      of GST-P foci in rat liver. Further attempt has been made to study the influence
      of astaxanthin on antioxidant response element (ARE) and the transcription factor
      Nrf2 (nuclear factor E(2)-related factor 2) in the induction of phase-II enzymes
      NAD(P)H: quinine oxidoreductase-1(NQO-1) and Hemoxygenase-1 (HO-1). Both pre- and
      post-treatment with astaxanthin (25mg/kg) decreased cyclophosphamide-induced
      oxidative stress and DNA damage in the liver as evident from the restoration in
      malondialdehyde and glutathione level as well as modified comet assay parameters.
      Significant decrease in the number as well as area of GST-P foci in rat
      hepatocytes was observed with astaxanthin post-treatment. Treatment with
      astaxanthin significantly decreased the expression of p53 and p38 as compared to
      cyclophosphamide treated group. It was further observed that the level of Nrf2
      and phase-II enzymes, i.e. NQO-1 and HO-1 were increased with astaxanthin
      treatment. The present study confirms that astaxanthin is a potent antioxidant
      and attenuates oxidative stress, DNA damage, cell death as well as induction of
      early hepatocarcinogenesis in rat induced by cyclophosphamide. Our results
      provide the evidence that one of the mechanism of chemoprotection offered by
      astaxanthin is mediated through Nrf2-ARE pathway.

PMID- 20038456
TI  - Structure-function studies of blood and air capillaries in chicken lung using 3D
      electron microscopy.
AB  - Avian pulmonary capillaries differ from those of mammals in three important ways.
      The blood-gas barrier is much thinner, it is more uniform in thickness, and the
      capillaries are far more rigid when their transmural pressure is altered. The
      thinness of the barrier is surprising because it predisposes the capillaries to
      stress failure. A possible mechanism for these differences is that avian
      pulmonary capillaries, unlike mammalian, are supported from the outside by air
      capillaries, but the details of the support are poorly understood. To clarify
      this we studied the blood and air capillaries in chicken lung using transmission
      electron microscopy (EM) and two relatively new techniques that allow 3D
      visualization: electron tomography and serial block-face scanning EM. These
      studies show that the pulmonary capillaries are flanked by epithelial bridges
      composed of two extremely thin epithelial cells with large surface areas. The
      junctions of the bridges with the capillary walls show thickening of the
      epithelial cells and an accumulation of extracellular matrix. Collapse of the
      pulmonary capillaries when the pressure outside them is increased is apparently
      prevented by the guy wire-like action of the epithelial bridges. The enlarged
      junctions between the bridges and the walls could provide a mechanism that limits
      the hoop stress in the capillary walls when the pressure inside them is
      increased. The support of the pulmonary capillaries may also be explained by an
      interdependence mechanism whereby the capillaries are linked to a rigid
      assemblage of air capillaries. These EM studies show the supporting structures in
      greater detail than has previously been possible, particularly in 3D, and they
      allow a more complete analysis of the mechanical forces affecting avian pulmonary
      capillaries.

PMID- 20038457
TI  - Propofol abolished the phrenic long-term facilitation in rats.
AB  - The aim was to investigate the effect of propofol anesthesia on the phrenic long
      term facilitation (pLTF) in rats. We hypothesized that pLTF would be abolished
      during propofol-compared with urethane anesthesia. Fourteen adult, male,
      anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley
      rats (seven per group), were exposed to the acute intermittent hypoxia (AIH)
      protocol. Peak phrenic nerve activity (PNA), burst frequency (f), and breathing
      rhythm parameters (Ti, Te, Ttot) were analyzed during the first hypoxia (TH1), as
      well as at 15 (T15), 30 (T30), and 60min (T60) after the final hypoxic episode,
      and compared to the baseline values. In propofol-anesthetized rats no significant
      changes of PNA were recorded after the last hypoxic episode, i.e. no pLTF was
      induced. There was a significant increase of PNA (59.4+/-6.6%, P<0.001) in
      urethane-anesthetized group at T60. AIH did not elicit significant changes in f,
      Ti, Te, Ttot in either group at T15, T30, and T60. The pLTF, elicited by AIH, was
      induced in the urethane-anesthetized rats. On the contrary, pLTF was abolished in
      the propofol-anesthetized rats.

PMID- 20038458
TI  - Visual search for real world targets under conditions of high target-background
      similarity: Exploring training and transfer in younger and older adults.
AB  - Real world visual search tasks often require observers to locate a target that
      blends in with its surrounding environment. However, studies of the effect of
      target-background similarity on search processes have been relatively rare and
      have ignored potential age-related differences. We trained younger and older
      adults to search displays comprised of real world objects on either homogenous
      backgrounds or backgrounds that camouflaged the target. Training was followed by
      a transfer session in which participants searched for novel camouflaged objects.
      Although older adults were slower to locate the target compared to younger
      adults, all participants improved substantially with training. Surprisingly,
      camouflage-trained younger and older adults showed no performance decrements when
      transferred to novel camouflage displays, suggesting that observers learned age
      invariant, generalizable skills relevant for searching under conditions of high
      target-background similarity. Camouflage training benefits at transfer for older
      adults appeared to be related to improvements in attentional guidance and target
      recognition rather than a more efficient search strategy.

PMID- 20038459
TI  - Complete assignment of (1)H and (13)C NMR spectra of standard neo-iota-carrabiose
      oligosaccharides.
AB  - Standard Eucheuma denticulatum iota-carrageenan was degraded with the Alteromonas
      fortis iota-carrageenase. The most abundant products, the neo-iota-carratetraose
      and neo-iota-carrahexaose were purified by permeation gel chromatography, and
      their corresponding (1)H and (13)C NMR spectra were fully assigned.

PMID- 20038460
TI  - A cell permeant peptide containing the cytoplasmic tail sequence of Fc receptor
      type IIA reduces calcium signaling and phagolysosome formation in neutrophils.
AB  - Receptors for the Fc domain of IgG mediate target recognition, signal
      transduction, and effector functions including antibody-dependent cytolysis,
      phagocytosis, and phagolysosome formation. To better understand FcR-mediated
      functions and to identify potential therapeutic strategies, we employed cell
      penetrating ("Trojan") peptides to deliver "wild-type" (LTL) or modified (AAA)
      FcgammaRIIA tail sequences to the neutrophil's cytoplasm. The Trojan-LTL peptide
      appeared to label the endoplasmic reticulum whereas the Trojan-AAA peptide
      distributed throughout the cytoplasm. The Trojan-LTL peptide, but not the Trojan
      AAA peptide, decreased Ca(2+) signaling at the phagosome and reduced
      phagolysosome formation. These studies suggest that FcgammaRIIA's tail can act as
      a peptide decoy thereby blunting FcgammaRIIA-mediated processes, which, in turn,
      suggests a possible route in managing inflammatory tissue damage.

PMID- 20038461
TI  - A tolerogenic semimature dendritic cells induce effector T-cell
      hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells
      that promotes skin allograft survival in mice.
AB  - Semimature dendritic cells (smDCs) can induce autoimmune tolerance by activation
      of host antigen-specific CD4(+)CD25(+) regulatory T (Treg) cells. We hypothesized
      that donor smDCs injected into recipients would induce effector T-cell
      hyporesponsiveness by activating CD4(+)CD25(+)Treg cells, and promote skin
      allograft survival. Myeloid smDCs were derived from C57BL/6J mice (donors) in
      vitro. BALB/c mice (recipients) were injected with smDCs to generate antigen
      specific CD4(+)CD25(+)Treg cells in vivo. Allograft survival was prolonged when
      BALB/c recipients received either C57BL/6J smDCs prior to grafting or C57BL/6J
      smDC-derived CD4(+)CD25(+)Treg cells post-grafting, and skin flaps from these
      grafts showed the highest IL-10 production regardless of rapamycin treatments.
      Our findings confirm that smDCs constitute an independent subgroup of DCs that
      play a key role for inducing CD4(+)CD25(+)Treg cells to express high IL-10
      levels, which induce hyporesponsiveness of effector T cells. Pre-treating
      recipients with donor smDCs may have potential for transplant tolerance
      induction.

PMID- 20038462
TI  - G-protein-coupled receptor independent, immunomodulatory properties of chemokine
      CXCL9.
AB  - Certain chemokines possess anti-angiogenic and antibacterial activity, in
      addition to their ability to recruit leukocytes. Herein, we demonstrate that
      CXCL9/MIG induces the expression, by a monocytic cell line and peripheral blood
      mononuclear cells, of a variety of chemokines including CXCL8/IL-8, CCL3/MIP
      1alpha, CCL4/MIP-1beta, CCL2/MCP-1 in a pertussis toxin insensitive manner.
      Similarly, another cationic chemokine CCL20/MIP-3alpha, but not the non-cationic
      chemokines CCL2 or CCL3, stimulated monocytic cells to produce substantial
      amounts of CXCL8 and CCL3. Microarray experiments demonstrated that CXCL9, but
      not CCL2, induced the expression of hundreds of genes, many of which have known
      or proposed immunomodulatory functions. Induction of CXCL8 required the p38 and
      ERK1/2 mitogen-activated protein kinases but not NFkappaB, JAK-STAT or JNK
      signaling pathways. These results collectively demonstrate that CXCL9 has
      immunomodulatory functions that are not mediated through a G-protein coupled
      receptor and may possess additional roles in host defenses against infection.

PMID- 20038464
TI  - Investigating the importance of the least supported phoneme on visual word
      naming.
AB  - The least supported phoneme refers to the phoneme position within a word with
      which the fewest phonological neighbors overlap. Recently, it has been argued
      that the number of neighbors coinciding with the least supported phoneme is a
      critical determinant of pronunciation latencies. The current research tested this
      claim by comparing naming latencies to words that differed in terms of the number
      of neighbors overlapping with their least supported phoneme. The results revealed
      that words where many neighbors overlapped were named more rapidly than those
      where few neighbors overlapped. These results are explained using the dual-route
      cascaded model of reading aloud.

PMID- 20038463
TI  - Expression and functional analyses of liver expressed antimicrobial peptide-2
      (LEAP-2) variant forms in human tissues.
AB  - The antimicrobial peptide Liver Expressed Antimicrobial Peptide-2 (LEAP-2) is
      proposed to function as part of the vertebrate innate immune system. However, the
      highly conserved nature of the LEAP-2 peptide primary structure among vertebrates
      suggests more fundamental physiological roles. RT-PCR analyses confirmed
      expression of LEAP-2 mRNA variants in human gastro-intestinal (GI) epithelial
      tissues and THP-1 monocytes. Three cDNA products indicative of at least three
      different spliced transcripts were observed. Translation of the cDNA sequences
      supported synthesis of transcripts encoding the secreted LEAP-2 peptide and two
      variants lacking signal sequences suggesting intracellular localisation. The
      synthesis and cytoplasmic localisation of LEAP-2 peptides in epithelia was
      supported by immunohistochemical analyses. Functional data suggested that LEAP-2
      is not involved in the physiological response of GI epithelia to iron, nor is it
      mitogenic for epithelial cells or chemotactic for THP-1 monocytes. However,
      changes in the LEAP-2 transcript patterns associated with the challenge of THP-1
      monocytes with lipopolysaccharide (100ng/ml) were supportive of the peptides
      having multiple roles in the innate immune response.

PMID- 20038465
TI  - Microwave-assisted extraction: Application to the determination of emerging
      pollutants in solid samples.
AB  - Flame retardants, surfactants, pharmaceutical and personal care products, among
      other compounds, have been the object of numerous environmental studies. In this
      chapter, the application of microwave-assisted extraction (MAE) in the
      development of analytical methods for several groups of organic compounds with
      growing concern as emerging pollutants has been considered. Compared to other
      extraction techniques, optimization of MAE experimental conditions is rather easy
      owing to the low number of influential parameters (i.e. matrix moisture, nature
      of the solvent, time, power, and temperature in closed vessels). The great
      reduction in the extraction time and solvent consumption, as well as the
      possibility of performing multiple extractions, increasing the sample throughput,
      can also be highlighted among MAE advantages. In summary, the study of several
      applications of MAE to environmental problems demonstrates that this technique
      constitutes a good alternative for the determination of organic compounds in
      environmental samples. It can be used as a rapid screening tool, and also to
      obtain detailed information on the sources, behaviour and fate of emerging
      pollutants in environmental matrices.

PMID- 20038466
TI  - Phase behavior in a ternary lipid membrane estimated using a nonlinear response
      surface method and Kohonen's self-organizing map.
AB  - A novel method for investigating phase behavior in a ternary lipid membrane was
      developed and tested. Sixty-five model membranes composed of sphingomyelin (SM),
      dioleoyl phosphatidylcholine (DOPC), and cholesterol (Ch) were prepared, and
      fluorescence anisotropy between 25 degrees C and 60 degrees C was measured.
      Observed fluorescence anisotropy curves as functions of temperature were analyzed
      using a nonlinear response surface method and Kohonen's self-organizing map.
      Thus, we generated a scatter plot indicating the distribution of membranes with
      similar membrane properties. The scatter plot showed that the SM/DOPC/Ch
      membranes resolved into six clusters with distinct membrane properties. We then
      conducted differential scanning calorimeter (DSC) measurement of membranes
      typical of the clusters. The results indicated that the membranes consisted of
      several phase domains (i.e., L(alpha), L(beta), l(o) phase domains), and the
      clusters were distinguished by differences in the type and content of membrane
      domain. This method is accurate because the clusters were determined based on
      experimental values. This technique is useful for elucidating the phase behavior
      of ternary lipid membranes. These findings contribute to clarification of domain
      formation.

PMID- 20038467
TI  - Synthesis of sulfur nanoparticles in aqueous surfactant solutions.
AB  - Sulfur is a widely used element in different applications such as fertilizers,
      pharmaceuticals, rubber, fiber industries, bioleaching processes, anti microbial
      agents, insecticides, and fumigants, etc. Nanosize sulfur particles are useful
      for pharmaceuticals, modification of carbon nano tubes, and synthesis of nano
      composites for lithium batteries. In this study we report a surfactant assisted
      route for the synthesis of sulfur nanoparticles by an acid catalyzed
      precipitation of sodium thiosulphate. We use both the inorganic and organic
      acids, and find that organic acid gives lower size sulfur particles. The size of
      the particles also depends on the reactant concentration and acid to reactant
      ratio. The effect of different surfactants (TX-100, CTAB, SDBS, and SDS) on
      particle size shows that the surfactant can significantly reduce the particle
      size without changing the shape. The size reducing ability is not same for all
      the surfactants, depending on the type of surfactant. The anionic surfactant SDBS
      is more effective for obtaining a uniform size in both the acid media. Whereas,
      the lowest size (30 nm) particles were obtained in a certain reactant
      concentration range using CTAB surfactant. The objective of this study is to
      synthesize sulfur nanoparticles in aqueous media and also study the effect of
      different surfactants on particle size.

PMID- 20038468
TI  - Bubble formation on a submerged micronozzle.
AB  - This work investigates detailed formation of air bubbles on a submerged
      micrometer-sized nozzle. The experimental study is conducted on a submerged
      nozzle of radius of 55 microm under low gas flow rate conditions (0.015-0.83
      ml/min). The bubble formation is recorded by a high-speed optical camera and
      detailed characteristics of bubble formation such as the variations of
      instantaneous contact angles, bubble heights and the radii of contact lines are
      obtained, which shows a weak dependence on the flow rate under the conditions of
      current work. Using experimentally captured values of the height of bubble and
      the radius of contact line, the Young-Laplace equation is solved, which is found
      to be able to predict the bubble evolution quite well until the last milliseconds
      before the detachment. A force analysis of bubble formation reveals that the
      observed variations of contact angles and other characteristics during the bubble
      growth period are associated with the relative contribution of surface tension,
      buoyancy force and gravitational force.

PMID- 20038469
TI  - Formulation and characterization of microemulsions based on mixed nonionic
      surfactants and peppermint oil.
AB  - Water/sucrose laurate/ethoxylated mono-di-glyceride/ethanol/peppermint oil
      microemulsion systems were formulated and characterized using electrical
      conductivity, dynamic viscosity, nuclear magnetic resonance, dynamic light
      scattering, small angle X-ray scattering and cryogenic transmission electron
      microscopy. The solubilization capacity of water in the oil is dependent on the
      surfactants and ethanol/oil mixing ratios (w/w). Static percolation phenomena
      were observed in these systems, and the water volume fraction percolation
      threshold was determined. A progressive transformation of the water-in-oil to
      bicontinuous and inversion to oil-in-water microemulsions occurs upon dilution
      with water, which was revealed by the determination of the diffusion coefficients
      of both oil and water inside the microemulsions. The diffusion coefficients of
      the surfactants at the interface of the microemulsions increase with increasing
      water volume fraction. The periodicity of the microemulsions increases linearly
      with increasing water volume fraction. In addition, the correlation length
      increases with water volume fraction to a certain value then decreases. Cryo-TEM
      images of the oil-in-water microemulsions revealed the presence of spheroidal
      droplets of up to 12 nm diameter.

PMID- 20038470
TI  - Type B thymoma: is prognosis predicted only by World Health Organization
      classification?
AB  - OBJECTIVE: The prognostic relevance of subtypes within type B thymomas is
      controversial. The objective of this study was to evaluate the utility of World
      Health Organization (WHO) classification in patients with type B thymoma.
      METHODS: This was a retrospective review of 100 patients who underwent thymectomy
      for WHO type B thymoma. Recurrence patterns and survival were compared among
      subtypes. RESULTS: There were 22 type B1 tumors, 43 type B2 tumors, and 35 type
      B3 tumors. Incomplete resection occurred in 5 patients with type B1 thymoma, 8
      with type B2 thymoma, and 8 with type B3 thymoma (P = .87). Of the 79 patients
      with complete resection, tumor recurrence occurred in 1 (5.9%) patient with type
      B1 thymoma, 2 (5.7%) with type B2 thymoma, and 2 (7.4%) with type B3 thymoma, and
      all of these patients had Masaoka stage III disease. Disease-free survival at 5
      years was 93%, 85%, and 82% in type B1, B2, and B3, respectively (B1 vs B2; P =
      .79; B2 vs B3; P = 0.6). Disease-free survival at 5 years was 94%, 100%, 61%, and
      50% in Masaoka stages I, II, III, and IV, respectively (I vs II; P = .26; II vs
      III; P = .028; III vs IV; P = .002). CONCLUSIONS: Tumor recurrence was
      significantly associated with advanced Masaoka stage regardless of the WHO
      subtype of type B thymomas. Given the heterogeneity of WHO type B thymomas,
      Masaoka stage should always be considered when predicting prognosis and planning
      adjuvant treatment for patients with type B thymomas.

PMID- 20038471
TI  - A new instrument of suction support adapter system for epicardial radiofrequency
      ablation.
AB  - OBJECTIVE: Recently, epicardial ablation on a beating heart has been conducted as
      a minimally invasive surgical procedure for atrial fibrillation. We have
      developed a suction support adapter with the aim of ensuring contact between the
      ablation probe and the atrial wall to obtain transmural coagulation, and we
      evaluated the effectiveness of the adapter in electrophysiologic and
      histopathologic procedures. METHODS: To ensure contact between the radiofrequency
      ablation probe and the atrial wall, we designed and fabricated a suction support
      adapter. Twelve pigs were used in this study. A comparison was made between a
      group in which the ablation probe alone was used (group C, n = 6) and a group in
      which the ablation probe was used with the adapter (group S, n = 6). In both
      groups, epicardial ablation was conducted on a beating heart. An
      electrophysiologic evaluation was conducted to determine whether there was
      electrical isolation. Histopathologic evaluations were performed to identify the
      range of coagulation in the resected atrial wall specimens. RESULTS: The
      coagulation range was significantly deeper in group S than in group C, and the
      breadth was significantly narrower. Transmural coagulation and electrical
      isolation of the atrial wall were seen in 1 case in group C and in all cases in
      group S. CONCLUSIONS: Using the suction support adapter, we were able to maintain
      good contact between the ablation probe and the atrial wall. This device is thus
      thought to be useful for the safe and reliable performance of epicardial ablation
      on a beating heart.

PMID- 20038472
TI  - The effectiveness of prestorage leukocyte-reduced red blood cell transfusion on
      perioperative inflammatory response with a miniaturized biocompatible bypass
      system.
AB  - OBJECTIVE: Since 2007, the Japanese Red Cross Blood Center has provided
      prestorage leukocyte-reduced red blood cell concentrates in which the leukocytes
      were reduced soon after collection. We have established a miniaturized bypass
      system (140 mL) to reduce the perioperative inflammatory responses. This study
      was designed to reveal the effectiveness of leukocyte-reduced red blood cell
      concentrate transfusion on perioperative inflammatory responses in pediatric
      cardiac surgery. METHODS: Between May 2006 and June 2008, 50 consecutive patients
      weighing less than 5 kg who underwent a surgical procedure with red blood cell
      concentrate transfusion using a miniaturized bypass system were reviewed
      retrospectively. Twenty-five patients before 2007 received stored red blood cell
      concentrate in which leukocytes were reduced with a filter just before
      transfusion (group A). After 2007, 25 patients received the prestorage leukocyte
      reduced red blood cell concentrate transfusion (group B). The postoperative peak
      C-reactive protein level, peak white blood cell count, peak neutrophil count,
      percentage body weight gain, inotrope score, plasma lactate concentration,
      postoperative mechanical ventilation time, and length of intensive care unit stay
      were compared as the perioperative inflammatory response and morbidity for both
      groups. RESULTS: There were no significant differences in peak white blood cell
      count, peak neutrophil count, percentage body weight gain, and inotrope score
      between the groups. The peak C-reactive protein level in group A was
      significantly greater than that in group B (6.7 +/- 4.7 vs 4.2 +/- 3.6 mg/dL, P <
      .05). The lactate concentration at 12 and 24 hours after surgical intervention in
      group A was significantly greater than that in group B (3.1 +/- 2.5 vs 1.9 +/-
      1.1 mmol/L [P < .05] and 2.2 +/- 0.2 vs 1.4 +/- 0.2 mmol/L [P < .05],
      respectively). The postoperative mechanical ventilation time and intensive care
      unit stay in group A were significantly greater than those in group B (5.9 +/-
      7.4 vs 2.1 +/- 2.0 days [P < .05] and 9.8 +/- 7.9 vs 5.0 +/- 2.1 days [P < 0.05],
      respectively). Multivariate analyses showed that the leukocyte-reduced red blood
      cell concentrate transfusion reduced the peak C-reactive protein level (in
      milligrams per deciliter; coefficient, -2.95; 95% confidence interval [CI], -4.66
      to -0.93; P = .003), postoperative mechanical ventilation time (in days;
      coefficient, -3.41; 95% CI, -6.07 to -0.74; P = .013), and intensive care unit
      stay (in days; coefficient, -4.51; 95% CI, -7.37 to -1.64; P = .003).
      CONCLUSIONS: Our study revealed that in neonates and small infants, compared with
      transfusions with stored red blood cell concentrate, transfusion of leukocyte
      reduced red blood cell concentrates was associated with reduced perioperative
      inflammatory responses and improved clinical outcomes.

PMID- 20038473
TI  - In vivo functional flowmetric behavior of the radial artery graft: is the
      composite Y-graft configuration advantageous over conventional aorta-coronary
      bypass?
AB  - INTRODUCTION: Intraoperative flowmetric results of different configurations (Y
      graft or aorta-coronary) of radial artery grafts have been poorly investigated.
      METHODS: We report the results of an observational study designed to analyze
      transit-time flow measurements at baseline and during 1:1 intra-aortic balloon
      pumping in 114 consecutive patients receiving the radial artery as a aorta
      coronary bypass (group A, 72 patients) or as a Y-graft with the left internal
      thoracic artery (group B, 42 patients). Graft flow reserve, recruited by 1:1
      intra-aortic balloon pumping) greater than 1 indicated recruitment of surplus
      graft flow. Results were stratified by grafted territory and surgical technique.
      RESULTS: Hospital outcome was comparable. Baseline transit-time flow results were
      similar between the 2 groups in terms of maximum diastolic flow, minimum systolic
      flow, mean flow, and pulsatility index. Graft flow reserve was not recruited by
      intra-aortic balloon pumping in 3 (2.7%) malfunctioning single aorta-oronary
      radial artery bypass grafts (P = .005 versus successful radial artery bypass
      grafts). Graft flow reserve was recruited (>1) by intra-aortic balloon pumping in
      the remaining 111 patent radial artery bypass grafts. Y-grafts showed higher
      maximum diastolic flow P < .0001), mean flow (P < .0001), graft flow reserve (P <
      .0001), percentage improvement of maximum diastolic flow (P < .0001), and of mean
      flow (P < .0001) compared with aorta-coronary radial artery bypass grafts. These
      results were confirmed for the right coronary (P < or = .004) and the circumflex
      territory (P < or = .001), for off-pump (P < or = .008) or cardiopulmonary bypass
      (P < .0001) and for patients undergoing isolated bypass grafting (P < .0001).
      CONCLUSIONS: Intraoperative flows of radial artery bypass grafts showed
      comparable baseline results in single aorta-coronary conduits and Y-grafts. Graft
      flow reserve recruited by intra-aortic balloon pumping was higher in Y-conduits,
      regardless of the grafted territory and the perfusion strategy chosen. Failed
      radial artery bypass grafts did not improve transit-time flow results during 1:1
      intra-aortic balloong pumping nor showed any recruitment of graft flow reserve.

PMID- 20038474
TI  - Avoiding cardiopulmonary bypass in extracardiac cavopulmonary connection: does it
      really matter?
AB  - OBJECTIVES: We examined the effect of avoiding cardiopulmonary bypass on the
      early outcome variables after fenestrated extracardiac total cavopulmonary
      connection. METHODS: Between May 2001 and January 2009, 102 patients with
      univentricular heart physiology underwent fenestrated extracardiac total
      cavopulmonary connection. Patients were divided into one of 2 groups: the
      cardiopulmonary bypass (n = 48) group and the no cardiopulmonary bypass (n = 54)
      group. In both groups there were patients with primary and staged fenestrated
      extracardiac total cavopulmonary connection. Duration of mechanical ventilation,
      pleural effusion, hemodynamic status, incidence of arrhythmia, and mortality were
      compared between the 2 groups. RESULTS: Both groups were matched, except for more
      cases of tricuspid atresia in the no cardiopulmonary bypass group (P = .014)
      compared with other diagnostic morphologies and higher preoperative hemoglobin
      levels in the no cardiopulmonary bypass group (P = .01). Avoiding cardiopulmonary
      bypass did not reveal any significant effect on postoperative outcomes. A
      cardiopulmonary bypass time of more than 120 minutes caused not only a meaningful
      increase in the mean of mechanical ventilation duration (35 +/- 9.6 vs 13 +/- 2.1
      hours, P = .026) but also increased the incidence of mechanical ventilation for
      more than 12 hours (P = .04). Bypass time of more than 120 minutes did not have
      influence on any other postoperative variables. CONCLUSION: Avoiding
      cardiopulmonary bypass in fenestrated extracardiac total cavopulmonary connection
      had no direct effect on the early outcome variables.

PMID- 20038475
TI  - Four-arm robotic lobectomy for the treatment of early-stage lung cancer.
AB  - OBJECTIVES: We investigated the feasibility and safety of four-arm robotic lung
      lobectomy in patients with lung cancer and described the robotic lobectomy
      technique with mediastinal lymph node dissection. METHODS: Over 21 months, 54
      patients underwent robotic lobectomy for early-stage lung cancer at our
      institute. We used a da Vinci Robotic System (Intuitive Surgical, Inc, Mountain
      View, Calif) with three ports plus one utility incision to isolate hilum elements
      and perform vascular and bronchial resection using standard endoscopic staplers.
      Standard mediastinal lymph node dissection was performed subsequently. Surgical
      outcomes were compared with those in 54 patients who underwent open surgery over
      the same period and were matched to the robotic group using propensity scores for
      a series of preoperative variables. RESULTS: Conversion to open surgery was
      necessary in 7 (13%) cases. Postoperative complications (11/54, 20%, in each
      group) and median number of lymph nodes removed (17.5 robotic vs 17 open) were
      similar in the 2 groups. Median robotic operating time decreased by 43 minutes (P
      = .02) from first tertile (18 patients) to the second-plus-third tertile (36
      patients). Median postoperative hospitalization was significantly shorter after
      robotic (excluding first tertile) than after open operations (4.5 days vs 6 days;
      P = .002). CONCLUSIONS: Robotic lobectomy with lymph node dissection is
      practicable, safe, and associated with shorter postoperative hospitalization than
      open surgery. From the number of lymph nodes removed it also appears
      oncologically acceptable for early lung cancer. Benefits in terms of
      postoperative pain, respiratory function, and quality of life still require
      evaluation. We expect that technologic developments will further simplify the
      robotic procedure.

PMID- 20038476
TI  - Characteristics and surgical outcomes of symptomatic patients with hypertrophic
      cardiomyopathy with abnormal papillary muscle morphology undergoing papillary
      muscle reorientation.
AB  - OBJECTIVE: In patients with hypertrophic cardiomyopathy with bifid hypermobile
      papillary muscles and a dynamic left ventricular outflow tract gradient, we
      performed surgical papillary muscle reorientation, fixing the mobile papillary
      muscle to the posterior left ventricle to reduce mobility. We report the outcomes
      of patients with hypertrophic cardiomyopathy undergoing surgical papillary muscle
      reorientation versus those of patients undergoing standard surgical procedures.
      METHODS: We studied 204 consecutive patients with hypertrophic cardiomyopathy
      undergoing surgical intervention (after consensus decision) for symptomatic left
      ventricular outflow tract gradient. Preoperative and postoperative maximal
      (resting/provocable) left ventricular outflow tract gradients were recorded by
      using echocardiographic analysis. RESULTS: The population was divided into 3
      groups: (1) isolated myectomy (n = 143; age, 54 +/- 14 years; 48% men), (2)
      myectomy plus mitral valve repair/replacement (n = 39; age, 54 +/- 13 years; 54%
      men), and (3) papillary muscle reorientation with or without myectomy (n = 22;
      age, 50 +/- 14 years; 59% men). The mean preoperative (103 +/- 32, 103 +/- 32,
      and 114 +/- 36 mm Hg; P = .3) and predischarge (15 +/- 18, 14 +/- 14, and 16 +/-
      21 mm Hg; P = .9) maximal left ventricular outflow tract gradients were similar.
      There were no deaths either in the hospital or at 30 days. At a median follow-up
      of 166 days (interquartile range, 74-343 days), 21 of 22 patients in group 3 were
      asymptomatic. One patient in group 3 had a symptomatic left ventricular outflow
      tract gradient (87 mm Hg) requiring mitral valve replacement. CONCLUSIONS: In
      patients with hypertrophic cardiomyopathy with bifid hypermobile papillary
      muscles (even with a basal septal thickness <1.5 cm), papillary muscle
      reorientation reduces the symptomatic left ventricular outflow tract gradient.
      Long-term outcomes need to be ascertained.

PMID- 20038477
TI  - Treatment of irradiated poststernotomy sternal nonunion with autologous stem cell
      impregnated bone matrix and sternal plating.

PMID- 20038478
TI  - Sustained local application of epidermal growth factor to accelerate
      reepithelialization of tracheal grafts.
AB  - OBJECTIVE: Epidermal growth factor-loaded gelatin microspheres were tested for
      potential to accelerate tracheal allograft reepithelialization. METHODS:
      Epidermal growth factor-loaded gelatin microspheres were prepared by optimal
      double-phase emulsified condensation polymerization. One hundred age-matched
      allogeneic mice were randomly allocated to local administration of 1 mg epidermal
      growth factor-loaded gelatin microspheres (containing 1 microg epidermal growth
      factor), 1 mg gelatin microspheres, 1 microg epidermal growth factor, or nothing
      (control, all groups n = 25) during orthotopic transplant of C57BL/6 donor
      tracheal segments into BALB/c recipients without immunosuppressors. On days 7,
      14, 21, 35, and 52 after transplant, 5 mice per group were killed and evaluated
      by histologic assessment and scanning electronic microscopy for
      reepithelialization and fibrosis of tracheal grafts. RESULTS: Mean diameter of
      gelatin microspheres was 107 microm. Microspheres could not be fully degraded
      until 35 days after transplant in vivo. On days 7, 14, and 21, epithelium score
      and ratio of lamina propria to tracheal cartilage were not statistically
      different between mice with epidermal growth factor-loaded gelatin microspheres
      and other groups. On days 35 and 52, however, epithelium score was higher and
      ratio of lamina propria to tracheal cartilage was lower in epidermal growth
      factor-loaded gelatin microsphere recipients; these mice also had almost complete
      differentiation of regenerated epithelium into ciliated columnar epithelium on
      days 35 and 52, earlier than in other groups. CONCLUSIONS: Gelatin microspheres
      act as a functional vector for epidermal growth factor. Sustained local
      application of epidermal growth factor could accelerate reepithelialization of
      tracheal allografts.

PMID- 20038479
TI  - Is robotic mitral valve repair a reproducible approach?
AB  - OBJECTIVE: We sought to review the surgical outcomes of our initial 120 robotic
      mitral valve repairs from June 2005 through April 2009. METHODS: The initial 74
      repairs were performed with the first-generation da Vinci robot (Intuitive
      Surgical, Inc, Sunny Vale, Calif), and the last 46 were performed with the da
      Vinci Si HD model. All patients received an annuloplasty band and 1 or more of
      the following: leaflet resection; annuloplasty; basal chord transposition,
      polytetrafluoroethylene neochordal replacement, or both; and edge-to-edge repair.
      RESULTS: The overall mean age was 58.4 +/- 10.5 years, and 64% were male. There
      was 1 (0.8%) hospital mortality. Five patients required mitral valve replacement
      for a failed repair. Another patient had mitral valve rerepair on postoperative
      day 2. Except for 2 early reoperations for postoperative bleeding, all of the
      complications and failed repairs requiring operative revision occurred with the
      original robot. Postdischarge transthoracic echocardiographic follow-up was
      available on 107 (93%) of 115 patients, with a median follow-up of 321 days. None
      to mild mitral regurgitation was seen in 102 (89%) patients, moderate mitral
      regurgitation was seen in 9 (8.4%) patients, and severe mitral regurgitation was
      seen in 3 (2.8%), with 1 patient undergoing mitral valve replacement and 2
      patients being medically managed. CONCLUSIONS: The majority of complications and
      all the repeat operations for failed mitral valve repair occurred with the older
      model da Vinci robot. The newer da Vinci Si HD system, with the addition of an
      adjustable left atrial roof retractor, improves mitral valve exposure, enhancing
      the surgeon's ability to repair and test the valve. We have progressed to
      successful repair of all types of degenerative mitral valve pathology and have
      found the approach reproducible.

PMID- 20038480
TI  - Electron transport chain dysfunction in neonatal pressure-overload hypertrophy
      precedes cardiomyocyte apoptosis independent of oxidative stress.
AB  - OBJECTIVES: We have previously shown in a model of pressure-overload hypertrophy
      that there is increased cardiomyocyte apoptosis during the transition from peak
      hypertrophy to ventricular decompensation. Electron transport chain dysfunction
      is believed to play a role in this process through the production of excessive
      reactive oxygen species. In this study we sought to determine electron transport
      chain function in pressure-overload hypertrophy and the role of oxidative stress
      in myocyte apoptosis. METHODS AND RESULTS: Neonatal rabbits underwent thoracic
      aortic banding at 10 days of age. Compensated hypertrophy (4 weeks of age),
      decompensated hypertrophy (6 weeks of age), and age-matched controls (n = 4-8 per
      group) as identified by serial echocardiography were studied. Electron transport
      chain complex activities were determined by spectophotometry in isolated
      mitochondria. Complex I was significantly decreased (P = .005) at 4 weeks and
      further decreased at 6 weeks (P = .001). Complex II was significantly decreased
      at both time points (4 weeks, P = .003; 6 weeks, P = .009). However, hyddrogen
      peroxide production, measured in isolated mitochondria by fluorescence
      spectroscopy, was significantly decreased at 4 weeks of age in banded animals
      compared with controls (P = .038), and mitochondrial DNA oxidative damage
      (measurement of 8- hydroxydeoxyguanosine by enzyme-linked immunosorbent assay)
      was also significantly decreased at 4 weeks of age (P = .031). Mitochondrial
      activated apoptosis was determined by Bax/Bcl-2 ratios (immunoblotting). Bax/Bcl
      2 levels were significantly increased in banded animals at 6 weeks. CONCLUSIONS:
      In pressure-overload hypertrophy, the transition from compensated left
      ventricular hypertrophy to failure and cardiomyocyte apoptosis is preceded by
      mitochondrial complex I and II dysfunction followed by an increase in Bax/Bcl-2
      ratios. The mechanism of apoptosis initiation is independent of increased
      oxidative stress.

PMID- 20038481
TI  - Effects of surgical ventricular reconstruction on diastolic function at midterm
      follow-up.
AB  - OBJECTIVE: Limited data are available on the effects of surgical ventricular
      reconstruction on diastolic function. The aim of the present study was to
      evaluate changes in diastolic function induced by surgical ventricular
      reconstruction at 2 time intervals after surgery (discharge and follow-up) and to
      assess the impact of diastolic changes on clinical outcome. METHODS: A total of
      129 patients (65 +/- 9 years, 14 women) underwent echocardiographic Doppler
      evaluation before surgical ventricular reconstruction, at discharge, and at
      follow-up (median 7 months). Patients with mitral regurgitation were excluded.
      Diastolic pattern was graded as follows: 0 (normal), 1 (abnormal relaxation), 2
      (pseudo normalization), 3 (restrictive, reversible), and 4 (restrictive,
      irreversible). RESULTS: At follow-up, 28 (21.7%) of 129 patients showed a
      restrictive diastolic pattern (grade 3-4; group 1) and 101 did not (diastolic
      pattern grade 0-2; group 2). Preoperative and postoperative factors strongly
      associated with late diastolic restriction included sphericity index (higher in
      group 1), ventricular shape (nonaneurysmal shape more frequent in group 1),
      internal dimensions (greater in group 1), diastolic pattern (higher in group 1),
      ejection fraction (lower in group 1); left atrial dimensions (greater in group
      1); mitral regurgitation rate (higher in group 1). At multivariate analysis the
      most powerful predictors of restriction were preoperative pseudonormalization of
      diastolic pattern (diastolic pattern 2) and septolateral dimensions (short axis).
      Overall, ejection fraction improved from 33% +/- 9% to 40% +/- 9% to 40% +/- 9%;
      P = .001; end-diastolic and end-systolic volumes decreased (112 +/- 41 to 73 +/-
      21 to 88 +/- 28 mL/m(2), respectively; P = .001; and 77 +/- 38 to 44 +/- 17 to 52
      +/- 24 mL/m(2), respectively; P = .001); New York Heart Association class
      improved (2.4 +/- 0.8 to 1.6 +/- 0.6; P = .001). CONCLUSIONS: Mild preoperative
      diastolic dysfunction (pseudonormalized pattern) and increased septolateral
      dimensions are independent predictors of diastolic restriction after surgical
      ventricular reconstruction.

PMID- 20038482
TI  - The successful application of simulation-based training in thoracic surgery
      residency.
AB  - OBJECTIVE: We developed and tested a clinical simulation program in the
      principles and conduct of cardiopulmonary bypass with the aim of improving
      confidence and proficiency in this critical aspect of cardiac surgical care.
      METHODS: Fifteen residents from 6 resident-training programs who reported no
      prior cardiopulmonary bypass observation or simulation-based perfusion experience
      participated in a cardiopulmonary bypass course involving both didactic lectures
      and hands-on simulation. A computer-controlled hydraulic model of the human
      circulation was used in a specifically designed multidisciplinary simulation
      center environment to give the participants hands-on training with both basic
      operations and specific perfusion crisis scenarios. Pretraining and posttraining
      assessments concerning confidence, knowledge, and applications with regard to
      cardiopulmonary bypass were administered and compared. RESULTS: Likert scale
      scores on confidence-related items increased significantly (P < .001), from 59%
      +/- 16% to 92% +/- 8%. Pretraining versus posttraining scores (72% +/- 14%) on
      similar cognitive items were not significantly different (P=.3636). Scores on
      similar open-ended application items before and after training improved from 62%
      +/- 25% to 85+/-10% (P < .0001). All subjects agreed that simulation-based
      cardiopulmonary bypass training was superior to classroom- and clinic-based
      education and that the scenarios enhanced their learning experience. CONCLUSIONS:
      Simulation-based cardiopulmonary bypass training appears to be an effective
      technique to build the confidence of thoracic surgery residents regarding
      knowledge and applications. Scenario-based practice in a specifically designed
      simulated environment is a valuable adjunct to traditional educational methods
      and has the potential to improve the training of thoracic residents.

PMID- 20038483
TI  - Immunosenescence and vaccination of the elderly II. New strategies to restore age
      related immune impairment.
AB  - One of the greatest health-care challenges in the elderly is to ensure that
      vaccination against infections are optimally effective, but vaccination can only
      be effective if cells that are capable of responding are still present in the
      repertoire. The reversing of immunosenescence could be achieved by improving
      immune responses or altering vaccine formulation. Recent vaccination strategies
      in the elderly exert low effectiveness. Nutritional interventions and moderate
      exercise delay T cell senescence. Telomerase activity and expression of toll-like
      receptors can be improved by chemotherapy. Reversion of thymic atrophy could be
      achieved by thymus transplantation, depletion of accumulated dysfunctional naive
      T cells and herpesvirus-specific exhausted memory cells. Administration of
      immunostimulatory and anti-inflammatory cytokines show the best practical
      approach. Reduced dendritic cell activity and co-receptor expression might be
      increased by interleukin (IL)-2 administration. IL-7 protects both B and T
      lymphocytes, but IL-2, IL-10, keratinocyte growth factor, thymic stromal
      lymphopoietin, as well as leptin and growth hormone also have a stimulatory
      effect on thymopoiesis. In animals, several strategies have been explored to
      produce more efficacious vaccines including high dose vaccines, DNA vaccines with
      immunostimulatory patch, virosomal vaccines and vaccines containing new
      adjuvants. Hopefully, one of these approaches will be translated into human
      therapy in a short time.

PMID- 20038484
TI  - High level association of mutation in KatG315 with MDR and XDR clinical isolates
      of Mycobacterium tuberculosis in Belarus.
AB  - The mutation in KatG315 is found in the majority of isoniazid resistant strains
      worldwide, especially in areas with a high incidence of tuberculosis. A total of
      138 isoniazid (INH)-resistant strains of Mycobacterium tuberculosis consisting of
      108 MDR (multidrug resistant) and 30 XDR (extensively drug resistant) isolated
      from patients in different regions of Belarus from 2007 to 2008 were screened by
      a PCR restriction fragment length polymorphism (RFLP) assay and sequencing. As a
      result, 97.8% prevalence of the KatG315 mutation was detected in all isolates
      from patients either actually or previously treated with tuberculosis. This
      mutation was not found in any of 9 INH-susceptible isolates and 2 standard
      strains of H37Rv and Academia included in the study. All isolates that contained
      the mutation in KatG315 were classified as MDR and XDR by a culture-based
      susceptibility testing method. Among the 30 XDR isolates, 15 (50%), 12 (40%), and
      3 (10%) were classified into principal genetic groups (PGG) 1, 2, and 3,
      respectively. It is concluded that INH-resistant MTB were associated with the
      mutated KatG315 phenotype. The simplicity of the assay, with 100% specificity,
      permits its implementation in routine practice at clinical microbiology
      laboratories for first and fast screening of cultures. This method has potential
      application for rapid diagnosis of INH resistance due to KatG315 mutation.

PMID- 20038485
TI  - Taguchi optimisation of a multiplex pneumococcal serotyping PCR and description
      of 11 novel serotyping primers.
AB  - Recently, a PCR-derived method for serotyping Streptococcus pneumoniae has been
      devised to substitute the conventional antiserum phenotypic method. The method
      initially used a multiplex PCR reaction, dividing the isolates into 6 different
      groups based on the detected PCR gel pattern. In order to optimise and refine
      this crucial step, the Taguchi technique was employed, which can evaluate the
      individual effect of six parameters (in this case: primers, MgCl2, nucleotide
      mix, polymerase and buffer), with only 18 experiments; varying the parameter
      levels in an orthogonal matrix which suppresses the interactions between them.
      With this method, clear and sharp bands were observed in 5 experiments out of the
      18, while the PCR did not work reliably in the remaining cases. In addition, the
      PCR-based technique could be rendered more economic by the 10-fold lowering of
      the quantities of two primers. The modified reaction yielded identical results to
      those obtained with the original method. Furthermore, we have designed serotype
      specific primers for 11 new serotypes. The most important ones are those that can
      distinguish the very closely related, but equally important serotypes 6A and 6B.

PMID- 20038486
TI  - A polyphasic study on the species diversity of the sediment microbiota of Lake
      Heviz.
AB  - Lake Heviz is the largest natural thermal lake of Europe, harboring special
      bacterial communities. The aim of the present study was to gain information about
      the distribution and species diversity of the sediment microbiota, with special
      focus on Actinobacteria, by using cultivation-based and -independent molecular
      methods. Samples from two depths were taken in two different locations in October
      2007. 245 strains were isolated, grouped to 85 OTUs by ARDRA, and identified by
      16S rDNA sequencing. Most of the strains showed highest sequence similarity with
      Bacillus and related genera. Strains belonging to the phylum Actinobacteria were
      identified as members of Arthrobacter, Brachybacterium, Brevibacterium,
      Curtobacterium, Friedmanniella, Gordonia, Kocuria, Microbacterium, Micrococcus,
      Micromonospora, Mycobacterium, Rhodococcus, Streptomyces and Williamsia . Two
      clone libraries were constructed from H3M and H4M samples, providing 288 and 192
      clones which were grouped to 150 and 125 OTUs, respectively, by ARDRA. The two
      most abundant group of the H4M library were OP8-related. The phylum
      Proteobacteria was represented mostly by delta-Proteobacteria, other relevant
      groups were Cyanobacteria, Bacteroidetes, Acidobacteria and beta-Proteobacteria.
      The H3M library was dominated by Cyanobacteria, Verrucomicrobia, beta
      Proteobacteria, gamma-Proteobacteria and delta-Proteobacteria. Chloroflexi,
      Bacteroidetes, Spirochetes and Firmicutes were scarce. Results from the clone
      libraries were compared to the length-heterogeneity-PCR fingerprints of the
      communities.

PMID- 20038487
TI  - Molecular biological investigations on the bacterial communities of curative well
      waters of Harkany Spa.
AB  - Bacterial communities from the sulfide containing curative well waters of Harkany
      Spa (Hungary) were investigated by cultivation independent molecular cloning and
      Denaturing Gradient Gel Electrophoresis (DGGE) methods between 2006 and 2008. The
      DGGE profiles of the bacterial communities originated from the wells of lukewarm
      waters showed seasonal similarities and were highly different from the thermal
      well. From the four clone libraries 22 different eubacterial species or genera
      were identified by sequence analysis. The majority of the clones of the lukewarm
      waters belonged to unidentified Epsilon-proteobacteria, Desulfocapsa sp. and
      Thiothrix spp., while the dominant clones of the thermal water were affiliated
      with the genus Denitratisoma sp. Most of the identified species and genera were
      related to bacteria with obligate or facultative chemolithotrophic sulfur
      metabolism, so the microbes of the curative waters may participate in the sulfur
      cycle of the wells.

PMID- 20038488
TI  - Usefulness of the QuantiFERON-TB-Gold in tube in a population at risk of bovine
      tubercular infection.
AB  - The effectiveness of the QuantiFERON-TB-Gold in tube was compared with PPD to
      detect tuberculosis infection in the staff of cattle-farms, as a consequence of
      an outbreak of bovine tuberculosis in livestock. The data revealed the advantage
      of the immunological test for the specific detection of subjects infected by
      Mycobacterium tuberculosis complex.

PMID- 20038489
TI  - Prevalence and antimicrobial resistance of uropathogens in different inpatient
      wards.
AB  - The predominant causative agent of urinary tract infections in children and
      adults is Escherichia coli , but it is necessary to appreciate the importance of
      other Gram-negative rods, especially in newborns. Antibiotic resistance rates are
      also different in children and in adult care units due to many factors and
      therapeutical guidelines.The aim of this retrospective study was to show the
      local prevalence and resistance patterns of uropathogens in certain clinics of
      university and present the distribution of uropathogens in different age groups.
      Therefore, 4833 positive samples were analysed. E. coli was found to be the
      highest prevalent causative agent in every adult care unit, but some differences
      in other causative agents could have been detected. Three types of antimicrobial
      agents showed decreasing susceptibility rates: trimethoprim/sulfamethoxasole,
      cephalosporins and quinolones; but there were differences in resistance among the
      8 investigated inpatient wards.

PMID- 20038490
TI  - Production and purification of low calcium response protein H of Chlamydophila
      pneumoniae.
AB  - Chlamydophila pneumoniae possesses a type III secretion system (TTSS), which
      allows the bacteria to secrete effector molecules into the inclusion membrane and
      into the cytosol of the host cell. Low calcium response protein H (LcrH), as a
      part of the TTSS, is a chaperone protein expressed from the middle to late stages
      of the chlamydial developmental cycle. Gene of LcrH (CPn0811) in a 6His-tagged
      form was cloned from C. pneumoniae CWL029, expressed and purified from
      Escherichia coli using the HIS-select TALON CellThru Resin. The purity was
      checked with mass spectrometry. The samples were used for immunization of BALB/c
      mice. The inducible E. coli clone, which over-expresses the chlamydial LcrH,
      permits the study of the biological properties of this protein.

PMID- 20038491
TI  - Virulence and antimicrobial resistance determinants of human pathogenic and
      commensal strains of Pseudomonas aeruginosa.

PMID- 20038492
TI  - Construction and immunogenicity of Salmonella vaccine vector expressing HIV-1
      antigen and MCP3.
AB  - This study aims to determine the efficacy of Salmonella enterica serovar
      Typhimurium STM-1 bearing MCP-3 gene as a delivery vehicle for the HIV gag gene
      (in particular p24 gene) and HIV env gene. The STM1 delivery HIV-p24 vaccination
      was carried out in the form of a recombinant or a DNA vaccine whereas only a DNA
      vaccine was used for HIV env . Naked DNA vaccination was also tested and immune
      responses were evaluated following immunisation in mouse model. RESULTS:
      vaccination cellular immune responses induced by recombinant p24 STM1 (STM1/pHly
      p24) were greater than those elicited by the p24 DNA vaccine in STM1 (STM1/VR
      p24), (but statistically not significant) than those induced by oral vaccination.
      However, IgA responses induced by oral vaccination with either a recombinant or
      DNA vaccine of p24 in STM1 are higher than those induced by IP vaccination. In
      addition, the numbers of cells secreting IL4 are reduced after oral vaccination
      with STM1/VR-p24/MCP3. However, for the HIV p24 antigen, STM1/MCP3 preferentially
      induces IFNgamma-secreting splenocytes. CONCLUSIONS: This result confirms other
      studies that Salmonella was able to deliver HIV antigens to the immune system and
      induced specific immune responses to the HIV antigen and for the HIV p24 antigen,
      STM1/MCP3 induces secretion of IFNgamma.

PMID- 20038493
TI  - Proteolytic activity of beef luncheon fungi as affected by incorporation of some
      food preservatives.
AB  - Screening of thirty-one fungal isolates (representing 16 genera, 28 species and 3
      varieties) collected from beef luncheon meat for their abilities to produce
      protease enzyme revealed that eleven isolates (35.48%) exhibited high protease
      production. However, fifteen isolates (48.39%) had moderate ability and 5
      isolates (16.13%) were low producers. Aspergillus flavus, Gibberella fujikuroi
      and Penicillium chrysogenum were the most active producers of protease. The
      incorporation of five chemical substances used as food preservatives (disodium
      phosphate, sodium benzoate, citric acid, potassium sorbate and sodium citrate)
      individually in the culture medium for protease production exhibited depressive
      effect on protease production as well as on mycelial growth of Aspergillus
      flavus, Gibberella fujikuroi and Penicillium chrysogenum , except in few cases
      the mycelial growth of A. flavus and G. fujikuroi was increased by the lowest
      concentration (100 ppm) of sodium benzoate, citric acid and disodium phosphate.

PMID- 20038494
TI  - The Human Gene Mutation Database: providing a comprehensive central mutation
      database for molecular diagnostics and personalized genomics.

PMID- 20038495
TI  - Detecting genes contributing to longevity using twin data.
AB  - Searching for genes contributing to longevity is a typical task in association
      analysis. A number of methods can be used for finding this association - from the
      simplest method based on the technique of contingency tables to more complex
      algorithms involving demographic data, which allow us to estimate the genotype
      specific hazard functions. The independence of individuals is the common
      assumption in all these methods. At the same time, data on related individuals
      such as twins are often used in genetic studies. This paper proposes an extension
      of the relative risk model to encompass twin data. We estimate the power and also
      discuss what happens if we treat the twin data using the univariate model.

PMID- 20038496
TI  - Identifying positive selection candidate loci for high-altitude adaptation in
      Andean populations.
AB  - High-altitude environments (>2,500 m) provide scientists with a natural
      laboratory to study the physiological and genetic effects of low ambient oxygen
      tension on human populations. One approach to understanding how life at high
      altitude has affected human metabolism is to survey genome-wide datasets for
      signatures of natural selection. In this work, we report on a study to identify
      selection-nominated candidate genes involved in adaptation to hypoxia in one
      highland group, Andeans from the South American Altiplano. We analysed dense
      microarray genotype data using four test statistics that detect departures from
      neutrality. Using a candidate gene, single nucleotide polymorphism-based
      approach, we identified genes exhibiting preliminary evidence of recent genetic
      adaptation in this population. These included genes that are part of the hypoxia
      inducible transcription factor ( HIF ) pathway, a biochemical pathway involved in
      oxygen homeostasis, as well as three other genomic regions previously not known
      to be associated with high-altitude phenotypes. In addition to identifying
      selection-nominated candidate genes, we also tested whether the HIF pathway shows
      evidence of natural selection. Our results indicate that the genes of this
      biochemical pathway as a group show no evidence of having evolved in response to
      hypoxia in Andeans. Results from particular HIF -targeted genes, however, suggest
      that genes in this pathway could play a role in Andean adaptation to high
      altitude, even if the pathway as a whole does not show higher relative rates of
      evolution. These data suggest a genetic role in high-altitude adaptation and
      provide a basis for genotype/phenotype association studies that are necessary to
      confirm the role of putative natural selection candidate genes and gene regions
      in adaptation to altitude.

PMID- 20038498
TI  - Evolutionary dynamics of olfactory receptor genes in chordates: interaction
      between environments and genomic contents.
AB  - Olfaction is essential for the survival of animals. Versatile odour molecules in
      the environment are received by olfactory receptors (ORs), which form the largest
      multigene family in vertebrates. Identification of the entire repertories of OR
      genes using bioinformatics methods from the whole-genome sequences of diverse
      organisms revealed that the numbers of OR genes vary enormously, ranging from
      approximately 1,200 in rats and approximately 400 in humans to approximately 150
      in zebrafish and approximately 15 in pufferfish. Most species have a considerable
      fraction of pseudogenes. Extensive phylogenetic analyses have suggested that the
      numbers of gene gains and losses are extremely large in the OR gene family, which
      is a striking example of the birth-and-death evolution. It appears that OR gene
      repertoires change dynamically, depending on each organism's living environment.
      For example, higher primates equipped with a well-developed vision system have
      lost a large number of OR genes. Moreover, two groups of OR genes for detecting
      airborne odorants greatly expanded after the time of terrestrial adaption in the
      tetrapod lineage, whereas fishes retain diverse repertoires of genes that were
      present in aquatic ancestral species. The origin of vertebrate OR genes can be
      traced back to the common ancestor of all chordate species, but insects,
      nematodes and echinoderms utilise distinctive families of chemoreceptors,
      suggesting that chemoreceptor genes have evolved many times independently in
      animal evolution.

PMID- 20038497
TI  - Cholinesterase inhibitors in Alzheimer's disease and Lewy body spectrum
      disorders: the emerging pharmacogenetic story.
AB  - This review provides an update on the current state of pharmacogenetic research
      in the treatment of Alzheimer's disease (AD) and Lewy body disease (LBD) as it
      pertains to the use of cholinesterase inhibitors (ChEI). AD and LBD are first
      reviewed from clinical and pathophysiological perspectives. This is followed by a
      discussion of ChEIs used in the symptomatic treatment of these conditions,
      focusing on their unique and overlapping pharmacokinetic and pharmacodynamic
      profiles, which can be used to identify candidate genes for pharmacogenetics
      studies. The literature published to date is then reviewed and limitations are
      discussed. This is followed by a discussion of potential endophenotypes which may
      help to refine future pharmacogenetic studies of response and adverse effects to
      ChEIs.

PMID- 20038500
TI  - R and Bioconductor solutions for alternative splicing detection.
AB  - The detection of alternative splicing using microarray technology involves
      multiple computational steps: normalisation, filtering, detection and
      visualisation. In this review, these analyses are approached using the R and
      Bioconductor open-source computation solution. There is some discussion on how to
      integrate different Bioconductor packages, and some of their major features are
      demonstrated. In addition, the Xmap Genome Browser is incorporated as an integral
      part of the analysis and annotation workflow.

PMID- 20038499
TI  - The mammalian aldehyde oxidase gene family.
AB  - Aldehyde oxidases (EC 1.2.3.1) are a small group of structurally conserved
      cytosolic proteins represented in both the animal and plant kingdoms. In
      vertebrates, aldehyde oxidases constitute the small sub-family of molybdo
      flavoenzymes, along with the evolutionarily and structurally related protein,
      xanthine oxidoreductase. These enzymes require a molybdo-pterin cofactor
      (molybdenum cofactor, MoCo) and flavin adenine dinucleotide for their catalytic
      activity. Aldehyde oxidases have broad substrate specificity and catalyse the
      hydroxylation of N-heterocycles and the oxidation of aldehydes to the
      corresponding acid. In humans, a single aldehyde oxidase gene ( AOX1 ) and two
      pseudogenes clustering on a short stretch of chromosome 2q are known. In other
      mammals, a variable number of structurally conserved aldehyde oxidase genes has
      been described. Four genes ( Aox1 , Aox3 , Aox4 and Aox3l1 ), coding for an
      equivalent number of catalytically active enzymes, are present in the mouse and
      rat genomes. Although human AOX1 and its homologous proteins are best known as
      drug metabolising enzymes, the physiological substrate(s) and function(s) are as
      yet unknown. The present paper provides an update of the available information on
      the evolutionary history, tissue- and cell-specific distribution and function of
      mammalian aldehyde oxidases.

PMID- 20038501
TI  - The aldehyde dehydrogenase gene superfamily resource center.
AB  - The website www.aldh.org is a publicly available database for nomenclature and
      functional and molecular sequence information for members of the aldehyde
      dehydrogenase (ALDH) gene superfamily for animals, plants, fungi and bacteria.
      The site has organised gene-specific records. It provides synopses of ALDH gene
      records, marries trivial terms to correct nomenclature and links global accession
      identifiers with source data. Server-side alignment software characterises the
      integrity of each sequence relative to the latest genomic assembly and provides
      identifier-specific detail reports, including a graphical presentation of the
      transcript's exon-intron structure, its size, coding sequence, genomic strand and
      locus. Also included are a summary of substrates, inhibitors and enzyme kinetics.
      The site provides reference lists and is designed to facilitate data mining by
      interested investigators.

PMID- 20038503
TI  - Physiological responses of Norway spruce (Picea abies) seedlings to drought
      stress.
AB  - Four-year-old seedlings of Picea abies [L.] Karst (Norway spruce) were grown in
      semi-controlled conditions with three watering regimes. The seedlings in the
      control group (c) were watered to prevent any dehydration effect. The two
      remaining groups were subjected to mild (ms) and severe water stress (ss),
      respectively. The following physiological variables were monitored until ss
      seedlings began to die: leaf water potential (psi(L)), stomatal conductance
      (g(s)), CO(2) exchange (P(N)), free proline content (Pro), total chlorophyll (a +
      b) concentration (Chl(t)) and the maximal photochemical efficiency of photosystem
      II (F(v)/F(m)). The results indicate that not all observed physiological
      parameters display the same degree of sensitivity to dehydration. After Day 12 of
      dehydration, psi(L) of ss seedlings was already significantly lower than that of
      the two other groups. On Day 26, significant differences in psi(L) were recorded
      among all treatments. Decreasing values of water potential were accompanied by
      early changes in P(N), g(s) and Pro. A significant decrease in Chl(t) and
      F(v)/F(m) were only observed during the more advanced stages of dehydration.
      These results demonstrate that the drought response of P. abies seedlings include
      a number of parallel physiological and biochemical changes in concert, enhancing
      the capability of plants to survive and grow during drought periods, but only to
      a point.

PMID- 20038504
TI  - Wood {delta}13C, {delta}18O and radial growth responses of residual red pine to
      variable retention harvesting.
AB  - Variable retention harvests are used to enhance the development of structural
      complexity in managed forests by retaining living trees and other structural
      legacies from the pre-harvest ecosystem. While harvesting should increase
      resource availability to residual trees, greater crown exposure may also increase
      environmental stress, which makes it difficult to predict growth in different
      structural environments. We used stable carbon isotope ratios (delta(13)C) of
      annual rings from red pine trees (Pinus resinosa Ait.) as an index of intrinsic
      water use efficiency (iWUE), the ratio of photosynthetic carbon assimilation (A)
      to stomatal conductance (g(s)), to better understand how differences in
      physiological performance relate to growth responses following harvests that left
      residuals dispersed, aggregated between small (0.1 ha) gaps or aggregated between
      large (0.3 ha) gaps. Stable oxygen isotope ratios (delta(18)O) were used as an
      index of g(s) to investigate the drivers behind changes in iWUE. Retention
      harvesting did not appear to affect delta(13)C or delta(18)O at the stand scale
      when compared to unharvested control stands, but there was a significant,
      negative correlation between residual tree delta(13)C and plot basal area in the
      second and third years after harvesting that suggests declining iWUE as overstory
      competition increases. Residual tree delta(18)O was similar across treatments and
      basal areas. Trees in variable retention harvests showed small but positive
      increases in radial growth from the pre-treatment to post-treatment measurement
      periods, while radial growth declined in unharvested control stands. There were
      no significant differences in radial growth among retention treatments. Our
      results suggest residual red pine in relatively open environments benefit from
      greater A but do not show evidence of changes in g(s) that would indicate altered
      water relations.

PMID- 20038505
TI  - Quantitative expression analysis of meristem identity genes in Eucalyptus
      occidentalis: AP1 is an expression marker for flowering.
AB  - A number of Eucalyptus species exhibit precocious flowering, flowering within a
      year of germination and often while still exhibiting juvenile foliage. To
      understand the nature of precocious flowering in Eucalyptus occidentalis, partial
      homologues of the inflorescence meristem identity gene TERMINAL FLOWER1 and of
      the floral meristem identity genes LEAFY and APETALA1 (EOTFL1, EOLFY and EOAP1,
      respectively) were isolated and characterized. The expression patterns of these
      meristem identity genes during the development of branched and single-stem plants
      were analysed by quantitative reverse transcriptase PCR. All E. occidentalis
      plants commenced flowering within 40 weeks of germination. However, the branched
      plants reached maximum flowering some 5-6 weeks earlier than did single-stem
      plants. Levels of EOTFL1 and EOLFY expression varied little during the study
      period irrespective of architecture treatment, whereas expression of EOAP1
      reached a peak coincident with peak flowering in both branched and single-stem
      plants. AP1 is clearly an expression marker for flowering in this species.

PMID- 20038506
TI  - A variety of research and clinical reviews from surgeons, intensive care
      physicians, cardiologists, pharmacologists, and anesthesiologists. Preface.

PMID- 20038507
TI  - Methylene blue: a simple marker for intraoperative detection of gastroduodenal
      perforations during laparoscopic pyloromyotomy.
AB  - INTRODUCTION: We studied the feasibility of using methylene blue (MB) as a marker
      to detect mucosal perforations during laparoscopic pyloromyotomy using in vitro
      and in vivo animal models. MATERIALS AND METHODS: MB was initially tested in pig
      stomachs in vitro. Information gathered from these experiments was then used to
      test the marker during experimental live piglet laparoscopic surgery. RESULTS: MB
      stained the gastric mucosa blue; this tint could be seen through the intact
      mucosal layer exposed via myotomy. Dye extravasation was seen during laparoscopic
      surgery with mucosal perforations of 1.2 mm and greater with or without air
      insufflation of the stomach. Air extravasation was seen with perforations of 2.0
      mm and greater. CONCLUSION: Full strength 1% MB dye instilled into the gastric
      lumen can potentially be used as a marker for detection of mucosal perforations
      of 1.2 mm or greater during laparoscopic pyloromyotomy.

PMID- 20038508
TI  - Masculinity in nontraditional occupations: ecological constructions.
AB  - The authors present Bronfenbrenner's ecological model as a conceptual framework
      to explore interlocking systemic and interpersonal influences on the development
      and perpetuation of men's gender role-related distress. To demonstrate the
      utility of this model, the authors present results from an exploratory
      qualitative study of men in nontraditional occupations. Using the constant
      comparison method, the authors' analysis of multiple interviews with elementary
      educators and medical support staff unearthed interwoven themes among the effects
      of cultural notions of masculinity on relationships, job tasks, and perceptions
      of themselves as men. Expectations about men (e.g., that men confront danger,
      remain calm in chaotic situations, and/or are predators) affected hiring
      decisions and interactions with colleagues, limited the scope of the men's work,
      and provided opportunities to reinforce traditional notions of masculinity and
      affirm the value of masculinity in their occupations. These different experiences
      all interacted to inform participants' senses of themselves as men.

PMID- 20038509
TI  - Measuring prenatal secondhand smoke exposure in mother-baby couplets.
AB  - INTRODUCTION: Pregnant women often underreport their smoking status and extent of
      secondhand smoke (SHS) exposure. Biomarker confirmation is the recommended method
      to assess smoking behaviors and SHS exposure in both mothers and infants.
      OBJECTIVES: The primary aims are to (a) examine the relationship between smoking
      behaviors and SHS exposure in mother-baby couplets using maternal and infant hair
      nicotine and maternal urine cotinine analyses and (b) determine whether there is
      an association between maternal and infant hair nicotine samples obtained shortly
      after birth. DISCUSSION: A cross-sectional study with a multiethnic sample of 210
      mother-baby couplets assessing SHS exposure. RESULTS: The level of maternal hair
      nicotine (MHN) was significantly different among three groups: nonsmoking,
      nonsmoking/passive exposed, and smoking (p < .0001), with nonsmoking and
      nonexposed women having the lowest level. Urine cotinine was strongly associated
      with self-reported smoking status (rho = .88; p < .0001). Maternal and infant
      hair nicotine were correlated, although MHN correlated more strongly with smoking
      status (rho = .46, p < .0001) than infant hair nicotine (rho = .39, p < .0001).
      CONCLUSIONS: MHN was a more precise biomarker of prenatal SHS exposure than
      infant hair nicotine; mothers' urine cotinine was strongly correlated with self
      reported smoking status.

PMID- 20038510
TI  - Prerelease intent predicts smoking behavior postrelease following a prison
      smoking ban.
AB  - INTRODUCTION: More than 2 million persons are incarcerated in the United States.
      Most are young minority men, soon to reenter the community. The majority are also
      lifelong smokers with high rates of health-related problems. As prisons implement
      smoking bans, it is not known whether health behavior change that is mandated,
      rather than selected, can be maintained. The Wisconsin Department of Corrections
      smoking ban is a unique opportunity to investigate determinants of smoking
      behavior after release from prison. METHODS: A convenience sample of 49
      incarcerated men near release participated in two interviews (1-month prerelease,
      in prison, and 1-month postrelease via telephone). Descriptive analyses and
      multivariate modeling were conducted to determine associations with postrelease
      smoking. RESULTS: Participants had a mean age of 36.7 years, 12.4 years of
      education, and a 2.3-year incarceration; 47% were Black and 41% White. They had
      smoked 14.5 years. Most (67%) believed that their health was improved after the
      smoking ban. Paired t tests revealed decreases in Positive and Negative Affect
      Scale negative affect (p = .001) and Patient Health Questionnaire-8 depression (p
      = .009) postrelease. Univariate analysis showed correlations of intent to smoke
      upon release with smoking relapse postrelease (p = .001), White race with smoking
      relapse postrelease (p = .045), and perceived better health since the prison
      smoking ban with nonsmoking on release (p = .01). There was a trend toward use of
      alcohol with smoking relapse on release (p = .061). DISCUSSION: Prerelease
      smoking intention predicted postrelease behavior. Belief in improved health after
      the prison smoking ban correlated with nonsmoking on release. Targeted relapse
      prevention interventions are needed for people reentering the community.

PMID- 20038511
TI  - Multiple myocardial infarctions in a 35 year-old woman with POEMS syndrome.

PMID- 20038512
TI  - An indicator of sudden cardiac death during brief coronary occlusion:
      electrocardiogram QT time and the role of collaterals.
AB  - AIMS: The coronary collateral circulation has a beneficial role regarding all
      cause and cardiac mortality. Hitherto, the underlying mechanism has not been
      clarified. The aim of this prospective study was to assess the effect of the
      coronary collateral circulation on electrocardiogram (ECG) QTc time change during
      short-term myocardial ischaemia. METHODS AND RESULTS: A total of 150 patients
      (mean age 63 +/- 11 years, 38 women) were prospectively included in this study.
      An ECG was recorded at baseline and during a standardized 1 min coronary balloon
      occlusion. QT interval was measured before, during, and after balloon occlusion
      and was corrected for heart rate (QTc). Simultaneously obtained collateral flow
      index (CFI), expressing collateral flow relative to normal anterograde flow, was
      determined based on intracoronary pressure measurements. During occlusion of the
      left anterior descending coronary artery mean QTc interval increased from 422 +/-
      33 to 439 +/- 36 ms (P < 0.001), left circumflex occlusion led to an increase
      from 414 +/- 32 to 427 +/- 27 ms (P < 0.001). QTc was not influenced by occlusion
      of the right coronary artery (RCA) (417 +/- 35 and 415 +/- 34 ms, respectively; P
      = 0.863). QTc change during occlusion of the left coronary artery was inversely
      correlated with CFI (R(2) = 0.122, P = 0.0002). CONCLUSION: Myocardial ischaemia
      leads to QT prolongation during a controlled 1 min occlusion of the left, but not
      the RCA. QT prolongation is inversely related to collateral function indicating a
      protective mechanism of human coronary collaterals against cardiac death.

PMID- 20038513
TI  - Transcatheter aortic valve implantation: predictors of procedural success--the
      Siegburg-Bern experience.
AB  - AIMS: The purpose of the present analysis was to identify predictors of
      procedural success of percutaneous transcatheter aortic valve implantation
      (TAVI). METHODS AND RESULTS: We prospectively assessed in-hospital outcome of
      patients undergoing TAVI at two institutions. We analysed clinical,
      morphological, and procedural parameters using univariate and multivariate
      regression models. Between 2005 and 2008, a total of 168 consecutive patients
      with symptomatic aortic valve stenosis underwent TAVI using the self-expanding
      CoreValve Revalving prosthesis. Patients (93%) were highly symptomatic with a New
      York Heart Association grade III/IV and a mean aortic valve area of 0.66 +/- 0.21
      cm(2). Acute and in-hospital procedural success rates were 90.5 and 83.9%,
      respectively, with an in-hospital mortality, myocardial infarction, and stroke
      rate of 11.9, 1.8, and 3.6%, respectively. Predictors of in-hospital procedural
      success were type of access (OR 0.33, 95% CI 0.13-0.82, P = 0.017), prior
      coronary intervention (OR 5.3, 95% CI 1.20-23.41, P = 0.028) and pre-procedural
      Karnofsky index using univariate regression. Pre-procedural Karnofsky index
      emerged as the only independent predictor (OR 1.04, 95% CI 1.00-1.08, P = 0.032)
      in the multivariate analysis. CONCLUSION: Pre-procedural functional performance
      status predicts the in-hospital outcome after TAVI. Patients with a good
      functional status are likely to benefit more from TAVI than previously reported
      high-risk patients.

PMID- 20038514
TI  - A reduction in bleeding in acute coronary syndromes? Let's not rain on the
      parade!

PMID- 20038515
TI  - Cost-effectiveness of adjuvant docetaxel for node-positive breast cancer
      patients: results of the PACS 01 economic study.
AB  - BACKGROUND: Using data from the PACS 01 randomized trial, we evaluated the cost
      effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus
      anthracyclines alone (FEC100) in patients with node-positive breast cancer.
      PATIENTS AND METHODS: Costs and outcomes were assessed in 1996 patients and the
      incremental cost-effectiveness ratios (ICERs) were estimated, using quality
      adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling
      fluctuations, confidence regions around the ICERs were calculated and cost
      effectiveness acceptability curves were drawn up. Sensitivity analyses were also
      carried out to assess the robustness of conclusions. RESULTS: The mean cost of
      treatment was 33% higher with strategy FEC-D, but this difference decreased to
      18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be
      9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The
      estimated probability that FEC-D was cost-effective reached >96% for a threshold
      of euro50 000 per QALY gained. If the price of taxane decreased slightly, the
      ICER would reach some very reasonable levels and this strategy would therefore be
      much more cost-effective. CONCLUSION: The sequential use of FEC100 followed by
      docetaxel appears to be a cost-effective alternative, even when uncertainty is
      taken into account.

PMID- 20038516
TI  - Methylation level of the RASSF1A promoter is an independent prognostic factor for
      clear-cell renal cell carcinoma.
AB  - BACKGROUND: Ras association domain family 1A (RASSF1A) is a tumor suppressor that
      regulates the cell cycle, apoptosis, and microtubule stability. The association
      between the methylation levels of RASSF1A and the prognosis of clear-cell renal
      cell carcinoma (CCRCC) remains unclear. Therefore, we investigated this
      relationship to determine the prognostic value of RASSF1A methylation levels for
      CCRCC. PATIENTS AND METHODS: The study comprised 179 Japanese patients who
      underwent radical or partial nephrectomy for CCRCC. The methylation level of 5'
      CpG islands in the RASSF1A was evaluated using combined bisulfite restriction
      analysis and bisulfite sequencing. RESULTS: High levels of methylation in the
      RASSF1A promoter were significantly more frequent in grade 3 compared with grade
      1 or 2 tumors (P = 0.028) and in patients with stage III or IV compared with
      patients with stage I or II (P = 0.043). Patients with high methylation levels
      had a significantly less favorable prognosis compared with those with low
      methylation levels (P = 0.040). Higher methylation levels were independently
      associated with a poor prognosis following multivariate analysis (P = 0.0053).
      CONCLUSION: These results indicate that quantitative promoter methylation levels
      of the RASSF1A gene may be a useful marker to predict the prognosis of CCRCC.

PMID- 20038518
TI  - Under what circumstances can process-based simulation models link genotype to
      phenotype for complex traits? Case-study of fruit and grain quality traits.
AB  - Detailed information has arisen from research at gene and cell levels, but it is
      still incomplete in the context of a quantitative understanding of whole plant
      physiology. Because of their integrative nature, process-based simulation models
      can help to bridge the gap between genotype and phenotype and assist in
      deconvoluting genotype-by-environment (GxE) interactions for complex traits.
      Indeed, GxE interactions are emergent properties of simulation models, i.e.
      unexpected properties generated by complex interconnections between subsystem
      components and biological processes. They co-occur in the system with synergistic
      or antagonistic effects. In this work, different kinds of GxE interactions are
      illustrated. Approaches to link model parameters to genes or quantitative trait
      loci (QTL) are briefly reviewed. Then the analysis of GxE interactions through
      simulation models is illustrated with an integrated model simulation of peach
      (Prunus persica (L.) Batsch) fruit mass and sweetness, and with a model of wheat
      (Triticum aestivum L.) grain yield and protein concentration. This paper suggests
      that the management of complex traits such as fruit and grain quality may become
      possible, thanks to the increasing knowledge concerning the genetic and
      environmental regulation of organ size and composition and to the development of
      models simulating the complex aspects of metabolism and biophysical behaviours at
      the plant and organ levels.

PMID- 20038517
TI  - Down-regulation of mitochondrial ATPase by hypermethylation mechanism in chronic
      myeloid leukemia is associated with multidrug resistance.
AB  - BACKGROUND: To identify novel proteins involved in multidrug resistance in
      chronic myeloid leukemia (CML). MATERIALS AND METHODS: Comparative proteomics was
      used to screen multidrug resistance-related proteins from K562 and K562/A02; the
      differently expressed proteins were further confirmed by western blot and real
      time PCR. short hairpin RNA (shRNA) assay was applied to determine the
      relationship between candidate protein and adriamycin resistance. Bisulfite
      sequencing was carried out to assess methylation status of candidate multidrug
      resistance-related gene promoter. K562/A02 was treated with 5-azacytidine or
      trichostatin A (TSA); multidrug resistance phenotype and corresponding protein or
      gene changes were detected. RESULTS: Seventeen proteins with altered abundances
      of more than twofold were detected, among which mitochondrial ATPase in K562/A02
      was significantly down-regulated. Suppressing mitochondrial ATPase by shRNA could
      enhance adriamycin resistance and antiapoptosis activity of K562. The promoter
      hypermethylation in mitochondrial ATPase was found to be attributed to the
      adriamycin-resistant phenotype of both K562/A02 (methylated frequency 18.18%) and
      CML primary cells in accelerated phase (methylated frequency 7.95%) or blast
      crisis (methylated frequency 26.59%). Inhibition of hypermethylation increased
      adriamycin sensitivity of K562/A02. A synergistic effect on reversing adriamycin
      resistant phenotype was obtained when 5-azacytidine was combined with TSA.
      CONCLUSION: Down-regulation of mitochondrial ATPase can lead to adriamycin
      resistance in CML and the mechanism is associated with DNA methylation
      regulation.

PMID- 20038519
TI  - B-cell anergy is maintained in anti-DNA transgenic NZB/NZW mice.
AB  - Clonal anergy has been well recognized as an important mechanism of B cell
      immunologic tolerance. However, the properties of anergic B cells and especially
      their role in the development of autoimmune disease in susceptible animals have
      been controversial. Here we show that low-affinity anti-DNA anergic B cells
      populate the mature B-cell compartment in the mouse spleen in excessive numbers
      and display paradoxical behavior in response to a combined B-cell receptor/TLR9
      activation. Surprisingly, B-cell anergy was maintained in aged NZB/NZW F1 mice
      that develop a systemic lupus erythematosus (SLE)-like autoimmune disease. In
      several parameters of anergy, such as calcium mobilization and antibody
      secretion, the lupus-prone mice appeared more anergic than their non-autoimmune
      counterparts. We conclude that low-affinity anergic B cells are unlikely to serve
      as precursors for the high-affinity autoreactive B cells that give rise to
      pathogenic anti-DNA auto-antibodies in SLE.

PMID- 20038520
TI  - Monitoring renal function in children with Fabry disease: comparisons of measured
      and creatinine-based estimated glomerular filtration rate.
AB  - BACKGROUND: Studies on renal function in children with Fabry disease have mainly
      been done using estimated creatinine-based glomerular filtration rate (GFR). The
      aim of this study was to compare estimated creatinine-based GFR (eGFR) with
      measured GFR (mGFR) in children with Fabry disease and normal renal function.
      METHODS: Eighty-two examinations were done in 42 children (24 boys, 18 girls)
      with Fabry disease from three different centres. The mean age was 12.3 years. GFR
      was measured with iohexol, Cr(51)-EDTA or iothalamate, and the mean mGFR was 108
      ml/min/1.73 m(2). RESULTS: The widely used original Schwartz formula (1976)
      overestimated GFR substantially by 50.6 ml/min/1.73 m(2) with a very low
      accuracy, whereas the new abbreviated Schwartz formula (2009) showed relatively
      good performances with a mean GFR overestimation of 5.3 ml/min/1.73 m(2) and 79%
      of the eGFR calculated within 20% of mGFR, thus being only slightly superior to
      the Counahan-Barratt formula. However, less than half of the eGFR calculated by
      the new abbreviated Schwartz equation were within 10% of the mGFR. When repeated
      measurements were performed, mGFR showed less variation than eGFR. CONCLUSIONS:
      The new abbreviated Schwartz formula should replace the original Schwartz formula
      in the routine follow-up of children with Fabry disease. The current creatinine
      based GFR formulas are all hampered by low accuracy in the 'creatinine-blind' GFR
      range, and early progressive disease may be missed. Supplemental mGFR is,
      therefore, recommended in patients where changes in GFR have potential impact on
      important treatment regimens. Cystatin C-based GFR formulas remain to be
      validated in Fabry children.

PMID- 20038521
TI  - Benefit of kidney transplantation beyond 70 years of age.
AB  - BACKGROUND: Kidney transplantation generally improves long-term survival in
      patients with end-stage renal disease. However, in patients older than 70 years
      of age, only limited data are available that directly compare the potential
      survival benefit of transplantation versus dialysis. METHODS: All patients aged
      above 70 years who started dialysis between 1990 and 2005 and were waitlisted for
      kidney transplantation were included in the study. They were categorized
      according to time periods of inclusion (1990-99 vs 2000-05). Survival rates of
      altogether 286 dialysis patients were analyzed with a Kaplan-Meier model, as well
      as with a time-dependent Cox model. Comparisons were made between those who
      received a transplant and those who did not, and further between the two time
      periods. RESULTS: Median age at inclusion was 73.6 years (interquartile range
      72.3-75.6). Two hundred and thirty-three patients (81%) received a kidney
      transplant during follow-up. Transplant recipients experienced an increased
      mortality in the first year after transplantation when compared to waitlisted
      patients. Patients starting dialysis between 1990 and 1999 had no significant
      long-term benefit of transplantation; HR for death 1.01 (0.58-1.75). In contrast,
      there was a substantial long-term benefit of transplantation among those starting
      dialysis after 2000; HR for death 0.40 (0.19-0.83), P = 0.014. CONCLUSIONS:
      Survival after kidney transplantation in patients over 70 years has improved
      during the last decade and offers a survival advantage over dialysis treatment.
      Our experience supports the use of kidney transplantation in this age group if an
      increased early post-operative risk is accepted. This transplant policy may be
      challenged for priority reasons.

PMID- 20038523
TI  - Calcium-activated chloride current amplifies the response to urine in mouse
      vomeronasal sensory neurons.
AB  - The vomeronasal organ (VNO) is an odor detection system that mediates many
      pheromone-sensitive behaviors. Vomeronasal sensory neurons (VSNs), located in the
      VNO, are the initial site of interaction with odors/pheromones. However, how an
      individual VSN transduces chemical signals into electrical signals is still
      unresolved. Here, we show that a Ca2+-activated Cl- current contributes
      approximately 80% of the response to urine in mouse VSNs. Using perforated patch
      clamp recordings with gramicidin, which leaves intracellular chloride
      undisrupted, we found that the urine-induced inward current (V(hold) = -80 mV)
      was decreased in the presence of chloride channel blockers. This was confirmed
      using whole cell recordings and altering extracellular chloride to shift the
      reversal potential. Further, the urine-induced currents were eliminated when both
      extracellular Ca2+ and Na+ were removed. Using inside-out patches from dendritic
      tips, we recorded Ca2+-activated Cl- channel activity. Several candidates for
      this Ca2+-activated Cl- channel were detected in VNO by reverse transcription
      polymerase chain reaction. In addition, a chloride cotransporter, Na+-K+-2Cl-
      isoform 1, was detected and found to mediate much of the chloride accumulation in
      VSNs. Collectively, our data demonstrate that chloride acts as a major amplifier
      for signal transduction in mouse VSNs. This amplification would increase the
      responsiveness to pheromones or odorants.

PMID- 20038524
TI  - Inactivation of the KcsA potassium channel explored with heterotetramers.
AB  - The tetrameric prokaryotic potassium channel KcsA is activated by protons acting
      on the intracellular aspect of the protein and inactivated through conformational
      changes in the selectivity filter. Inactivation is modulated by a network of
      interactions within each protomer between the pore helix and residues at the
      external entrance of the channel. Inactivation is suppressed by the E71A
      mutation, which perturbs the stability of this network. Here, cell-free protein
      synthesis followed by protein purification by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was used to produce heterotetramers of KcsA
      that contain different combinations of wild-type and E71A subunits. Single
      channel recordings from these heterotetramers reveal how the network of
      interactions in individual protomers affects ionic conduction and channel
      inactivation, suggesting that the latter is a cooperative process.

PMID- 20038525
TI  - Epac1 mediates protein kinase A-independent mechanism of forskolin-activated
      intestinal chloride secretion.
AB  - Intestinal Cl- secretion is stimulated by cyclic AMP (cAMP) and intracellular
      calcium ([Ca2+]i). Recent studies show that protein kinase A (PKA) and the
      exchange protein directly activated by cAMP (Epac) are downstream targets of
      cAMP. Therefore, we tested whether both PKA and Epac are involved in forskolin
      (FSK)/cAMP-stimulated Cl- secretion. Human intestinal T84 cells and mouse small
      intestine were used for short circuit current (I(sc)) measurement in response to
      agonist-stimulated Cl- secretion. FSK-stimulated Cl- secretion was completely
      inhibited by the additive effects of the PKA inhibitor, H89 (1 microM), and the
      [Ca2+]i chelator, 1,2-bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid,
      tetraacetoxymethyl ester (BAPTA-AM; 25 microM). Both FSK and the Epac activator 8
      pCPT-2'-O-Me-cAMP (50 microM) elevated [Ca2+]i, activated Ras-related protein 2,
      and induced Cl- secretion in intact or basolateral membrane-permeabilized T84
      cells and mouse ileal sheets. The effects of 8-pCPT-2'-O-Me-cAMP were completely
      abolished by BAPTA-AM, but not by H89. In contrast, T84 cells with silenced Epac1
      had a reduced I(sc) response to FSK, and this response was completely inhibited
      by H89, but not by the phospholipase C inhibitor U73122 or BAPTA-AM. The
      stimulatory effect of 8-pCPT-2'-O-Me-cAMP on Cl- secretion was not abolished by
      cystic fibrosis transmembrane conductance (CFTR) inhibitor 172 or glibenclamide,
      suggesting that CFTR channels are not involved. This was confirmed by lack of
      effect of 8-pCPT-2'-O-Me-cAMP on whole cell patch clamp recordings of CFTR
      currents in Chinese hamster ovary cells transiently expressing the human CFTR
      channel. Furthermore, biophysical characterization of the Epac1-dependent Cl-
      conductance of T84 cells mounted in Ussing chambers suggested that this
      conductance was hyperpolarization activated, inwardly rectifying, and displayed a
      Cl->Br->I- permeability sequence. These results led us to conclude that the Epac
      Rap-PLC-[Ca2+]i signaling pathway is involved in cAMP-stimulated Cl- secretion,
      which is carried by a novel, previously undescribed Cl- channel.

PMID- 20038526
TI  - The activation mechanism of alpha1beta2gamma2S and alpha3beta3gamma2S GABAA
      receptors.
AB  - The alpha1beta2gamma2 and alpha3beta3gamma2 are two isoforms of gamma
      aminobutyric acid type A (GABAA) receptor that are widely distributed in the
      brain. Both are found at synapses, for example in the thalamus, where they
      mediate distinctly different inhibitory postsynaptic current profiles,
      particularly with respect to decay time. The two isoforms were expressed in
      HEK293 cells, and single-channel activity was recorded from outside-out patches.
      The kinetic characteristics of both isoforms were investigated by analyzing
      single-channel currents over a wide range of GABA concentrations.
      Alpha1beta2gamma2 channels exhibited briefer active periods than
      alpha3beta3gamma2 channels over the entire range of agonist concentrations and
      had lower intraburst open probabilities at subsaturating concentrations.
      Activation mechanisms were constructed by fitting postulated schemes to data
      recorded at saturating and subsaturating GABA concentrations simultaneously.
      Reaction mechanisms were ranked according to log-likelihood values and how
      accurately they simulated ensemble currents. The highest ranked mechanism for
      both channels consisted of two sequential binding steps, followed by three
      conducting and three nonconducting configurations. The equilibrium dissociation
      constant for GABA at alpha3beta3gamma2 channels was approximately 2.6 microM
      compared with approximately 19 microM for alpha1beta2gamma2 channels, suggesting
      that GABA binds to the alpha3beta3gamma2 channels with higher affinity. A notable
      feature of the mechanism was that two consecutive doubly liganded shut states
      preceded all three open configurations. The lifetime of the third shut state was
      briefer for the alpha3beta3gamma2 channels. The longer active periods, higher
      affinity, and preference for conducting states are consistent with the slower
      decay of inhibitory currents at synapses that contain alpha3beta3gamma2 channels.
      The reaction mechanism we describe here may also be appropriate for the analysis
      of other types of GABAA receptors and provides a framework for rational
      investigation of the kinetic effects of a variety of therapeutic agents that
      activate or modulate GABAA receptors and hence influence synaptic and
      extrasynaptic inhibition in the central nervous system.

PMID- 20038527
TI  - Metachromatic leukodystrophy: a case of triplets with the late infantile variant
      and a systematic review of the literature.
AB  - Metachromatic leukodystrophy is a rare disorder with great clinical variability.
      We report the first case of triplets with the late infantile form of the disease
      and their systematic progression of symptoms. We reviewed the literature and
      identified all human studies that reported new cases since 1921. We analyzed
      survival by decade to assess the impact of historical changes in the management
      of care. Mean age at death and the 5-year survival from onset of symptoms for
      late infantile, juvenile, and adult phenotypes were 4.2 years and 24.9%, 17.4
      years and 70.3%, and 43.1 years and 88.6%, respectively. The 5-year survival of
      cases reported after 1990 was significantly better than cases reported before
      1970 in all subtypes of metachromatic leukodystrophy (late infantile: 52% vs 14%,
      juvenile: 100% vs 46%, adult: 95% vs 67%). Survival in the late infantile subtype
      was worse than that in other subtypes. Survival significantly improved over time
      in all subtypes.

PMID- 20038528
TI  - The ARF-like GTPase ARFRP1 is essential for lipid droplet growth and is involved
      in the regulation of lipolysis.
AB  - ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a GTPase regulating
      protein trafficking between intracellular organelles. Here we show that mice
      lacking Arfrp1 in adipocytes (Arfrp1(ad-/-)) are lipodystrophic due to a
      defective lipid droplet formation in adipose cells. Ratios of mono-, di-, and
      triacylglycerol, as well as the fatty acid composition of triglycerides, were
      unaltered. Lipid droplets of brown adipocytes of Arfrp1(ad-/-) mice were
      considerably smaller and exhibited ultrastructural alterations, such as a
      disturbed interaction of small lipid-loaded particles with the larger droplets,
      suggesting that ARFRP1 mediates the transfer of newly formed small lipid
      particles to the large storage droplets. SNAP23 (synaptosomal-associated protein
      of 23 kDa) associated with small lipid droplets of control adipocytes but was
      located predominantly in the cytosol of Arfrp1(ad-/-) adipocytes, suggesting that
      lipid droplet growth is defective in Arfrp1(ad-/-) mice. In addition, levels of
      phosphorylated hormone-sensitive lipase (HSL) were elevated, and association of
      adipocyte triglyceride lipase (ATGL) with lipid droplets was enhanced in brown
      adipose tissue from Arfrp1(ad-/-) mice. Accordingly, basal lipolysis was
      increased after knockdown of Arfrp1 in 3T3-L1 adipocytes. The data indicate that
      disruption of ARFRP1 prevents the normal enlargement of lipid droplets and
      produces an activation of lipolysis.

PMID- 20038529
TI  - Mutational analysis of the poly(ADP-ribosyl)ation sites of the transcription
      factor CTCF provides an insight into the mechanism of its regulation by poly(ADP
      ribosyl)ation.
AB  - Poly(ADP-ribosyl)ation of the conserved multifunctional transcription factor CTCF
      was previously identified as important to maintain CTCF insulator and chromatin
      barrier functions. However, the molecular mechanism of this regulation and also
      the necessity of this modification for other CTCF functions remain unknown. In
      this study, we identified potential sites of poly(ADP-ribosyl)ation within the N
      terminal domain of CTCF and generated a mutant deficient in poly(ADP
      ribosyl)ation. Using this CTCF mutant, we demonstrated the requirement of
      poly(ADP-ribosyl)ation for optimal CTCF function in transcriptional activation of
      the p19ARF promoter and inhibition of cell proliferation. By using a newly
      generated isogenic insulator reporter cell line, the CTCF insulator function at
      the mouse Igf2-H19 imprinting control region (ICR) was found to be compromised by
      the CTCF mutation. The association and simultaneous presence of PARP-1 and CTCF
      at the ICR, confirmed by single and serial chromatin immunoprecipitation assays,
      were found to be independent of CTCF poly(ADP-ribosyl)ation. These results
      suggest a model of CTCF regulation by poly(ADP-ribosyl)ation whereby CTCF and
      PARP-1 form functional complexes at sites along the DNA, producing a dynamic
      reversible modification of CTCF. By using bioinformatics tools, numerous sites of
      CTCF and PARP-1 colocalization were demonstrated, suggesting that such regulation
      of CTCF may take place at the genome level.

PMID- 20038530
TI  - Evolutionarily conserved function of RRP36 in early cleavages of the pre-rRNA and
      production of the 40S ribosomal subunit.
AB  - Ribosome biogenesis in eukaryotes is a major cellular activity mobilizing the
      products of over 200 transcriptionally coregulated genes referred to as the rRNA
      and ribosome biosynthesis regulon. We investigated the function of an essential,
      uncharacterized gene of this regulon, renamed RRP36. We show that the Rrp36p
      protein is nucleolar and interacts with 90S and pre-40S preribosomal particles.
      Its depletion affects early cleavages of the 35S pre-rRNA and results in a rapid
      decrease in mature 18S rRNA levels. Rrp36p is a novel component of the 90S
      preribosome, the assembly of which has been suggested to result from the stepwise
      incorporation of several modules, including the tUTP/UTP-A, PWP2/UTP-B, and UTP-C
      subcomplexes. We show that Rrp36p depletion does not impair the incorporation of
      these subcomplexes and the U3 small nucleolar RNP into preribosomes. In contrast,
      depletion of components of the UTP-A or UTP-B modules, but not Rrp5p, prevents
      Rrp36p recruitment and reduces its accumulation levels. In parallel, we studied
      the human orthologue of Rrp36p in HeLa cells, and we show that the function of
      this protein in early cleavages of the pre-rRNA has been conserved through
      evolution in eukaryotes.

PMID- 20038531
TI  - RAB26 and RAB3D are direct transcriptional targets of MIST1 that regulate
      exocrine granule maturation.
AB  - Little is known about how differentiating cells reorganize their cellular
      structure to perform specialized physiological functions. MIST1, an
      evolutionarily conserved transcription factor, is required for the formation of
      large, specialized secretory vesicles in gastric zymogenic (chief) cells (ZCs) as
      they differentiate from their mucous neck cell progenitors. Here, we show that
      MIST1 binds to highly conserved CATATG E-boxes to directly activate transcription
      of 6 genes, including those encoding the small GTPases RAB26 and RAB3D. We next
      show that RAB26 and RAB3D expression is significantly downregulated in Mist1(
      )(/)(-) ZCs, suggesting that MIST1 establishes large secretory granules by
      inducing RAB transcription. To test this hypothesis, we transfected human gastric
      cancer cell lines stably expressing MIST1 with red fluorescent protein (RFP)
      tagged pepsinogen C, a key secretory product of ZCs. Those cells upregulate
      expression of RAB26 and RAB3D to form large secretory granules, whereas control,
      non-MIST1-expressing cells do not. Moreover, granule formation in MIST1
      expressing cells requires RAB activity because treatment with a RAB prenylation
      inhibitor and transfection of dominant negative RAB26 abrogate granule formation.
      Together, our data establish the molecular process by which a transcription
      factor can directly induce fundamental cellular architecture changes by
      increasing transcription of specific cellular effectors that act to organize a
      unique subcellular compartment.

PMID- 20038532
TI  - H19 imprinting control region methylation requires an imprinted environment only
      in the male germ line.
AB  - The 2.4-kb H19 imprinting control region (H19ICR) is required to establish parent
      of-origin-specific epigenetic marks and expression patterns at the Igf2/H19
      locus. H19ICR activity is regulated by DNA methylation. The ICR is methylated in
      sperm but not in oocytes, and this paternal chromosome-specific methylation is
      maintained throughout development. We recently showed that the H19ICR can work as
      an ICR even when inserted into the normally nonimprinted alpha fetoprotein locus.
      Paternal but not maternal copies of the ICR become methylated in somatic tissue.
      However, the ectopic ICR remains unmethylated in sperm. To extend these findings
      and investigate the mechanisms that lead to methylation of the H19ICR in the male
      germ line, we characterized novel mouse knock-in lines. Our data confirm that the
      2.4-kb element is an autonomously acting ICR whose function is not dependent on
      germ line methylation. Ectopic ICRs become methylated in the male germ line, but
      the timing of methylation is influenced by the insertion site and by additional
      genetic information. Our results support the idea that DNA methylation is not the
      primary genomic imprint and that the H19ICR insertion is sufficient to transmit
      parent-of-origin-dependent DNA methylation patterns independent of its
      methylation status in sperm.

PMID- 20038534
TI  - Cell sorting-assisted microarray profiling of host cell response to
      Cryptosporidium parvum infection.
AB  - To study the transcriptional response of mammalian cells to infection with the
      intracellular apicomplexan parasite Cryptosporidium parvum, infected and
      uninfected cells were recovered from C. parvum-infected cell monolayers. This
      approach, which contrasts with a more conventional experimental design that
      compares infected to uninfected cell monolayers, enabled the identification of
      functional categories of genes that are differentially transcribed as a direct
      consequence of the presence of intracellular parasites. Among several categories
      of upregulated genes, glycoprotein metabolism was significantly overrepresented.
      To investigate whether these transcriptional changes affected the composition of
      the surface of infected cells, cells were probed with fluorescently labeled
      lectins. Among a panel of seven lectins, soybean agglutinin, which recognizes N
      acetyl-d-galactosamine, generated the largest difference in fluorescence between
      infected and uninfected cells. The origin of the fluorescent signal emitted by
      infected cells was further investigated and attributed to the overexpression of
      glycoprotein on the surface of infected cells, as well as the presence of
      glycoprotein located in the proximity of intracellular parasites.

PMID- 20038533
TI  - The hsp90-FKBP52 complex links the mineralocorticoid receptor to motor proteins
      and persists bound to the receptor in early nuclear events.
AB  - In this study, we demonstrate that the subcellular localization of the
      mineralocorticoid receptor (MR) is regulated by tetratricopeptide domain (TPR)
      proteins. The high-molecular-weight immunophilin (IMM) FKBP52 links the MR-hsp90
      complex to dynein/dynactin motors favoring the cytoplasmic transport of MR to the
      nucleus. Replacement of this hsp90-binding IMM by FKBP51 or the TPR peptide
      favored the cytoplasmic localization of MR. The complete movement machinery,
      including dynein and tubulin, could be recovered from paclitaxel/GTP-stabilized
      cytosol and was fully reassembled on stripped MR immune pellets. The whole MR
      hsp90-based heterocomplex was transiently recovered in the soluble fraction of
      the nucleus after 10 min of incubation with aldosterone. Moreover, cross-linked
      MR-hsp90 heterocomplexes accumulated in the nucleus in a hormone-dependent
      manner, demonstrating that the heterocomplex can pass undissociated through the
      nuclear pore. On the other hand, a peptide that comprises the DNA-binding domain
      of MR impaired the nuclear export of MR, suggesting the involvement of this
      domain in the process. This study represents the first report describing the
      entire molecular system that commands MR nucleocytoplasmic trafficking and
      proposes that the MR-hsp90-TPR protein heterocomplex is dissociated in the
      nucleus rather than in the cytoplasm.

PMID- 20038535
TI  - Assessment of live candidate vaccines for paratuberculosis in animal models and
      macrophages.
AB  - Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the
      causative agent of paratuberculosis, a chronic enteritis of ruminants. To control
      the considerable economic effect that paratuberculosis has on the livestock
      industry, a vaccine that induces protection with minimal side effects is
      required. We employed transposon mutagenesis and allelic exchange to develop
      three potential vaccine candidates, which were then tested for virulence with
      macrophages, mice, and goats. All three models identified the WAg906 mutant as
      being the most attenuated, but some differences in the levels of attenuation were
      evident among the models when testing the other strains. In a preliminary mouse
      vaccine experiment, limited protection was induced by WAg915, as evidenced by a
      reduced bacterial load in spleens and livers 12 weeks following intraperitoneal
      challenge with M. paratuberculosis K10. While we found macrophages and murine
      models to be rapid and cost-effective alternatives for the initial screening of
      M. paratuberculosis mutants for attenuation, it appears necessary to do the
      definitive assessment of attenuation with a ruminant model.

PMID- 20038536
TI  - Associations between mucosal innate and adaptive immune responses and resolution
      of diarrheal pathogen infections.
AB  - The identification of immune response mechanisms that contribute to the control
      of diarrheal disease in developing countries remains an important priority. We
      addressed the role of fecal chemokines and cytokines in the resolution of
      diarrheal Escherichia coli and Giardia lamblia infections. Stools collected from
      127 Mexican children 5 to 15 months of age enrolled in a randomized, double
      blind, placebo-controlled, vitamin A supplementation trial were screened for
      enteropathogenic Escherichia coli (EPEC), enterotoxigenic E. coli (ETEC), and
      Giardia lamblia. Fecal concentrations of tumor necrosis factor alpha (TNF-alpha),
      monocyte chemoattractant protein-1 (MCP-1), interleukin-4 (IL-4), IL-5, IL-6, IL
      8, IL-10, and interferon-gamma (IFN-gamma) were determined. Hazard models
      incorporating cytokine variables were fit to durations of asymptomatic and
      symptomatic pathogen infections, controlling for treatment group. Increased
      levels of TNF-alpha and IL-6 were associated with decreased durations of EPEC
      infection and increased ETEC durations. Increased IL-4 and IFN-gamma levels were
      associated with decreased and increased durations, respectively, of both EPEC and
      ETEC infections. Increased IL-10 levels were associated with increased and
      decreased durations of asymptomatic and symptomatic EPEC infections,
      respectively, and increased durations of both asymptomatic and symptomatic ETEC
      infections. Increased levels of MCP-1, IFN-gamma, IL-4, and IL-5 were associated
      with increased G. lamblia infection duration, while increased IL-8 levels were
      associated with decreased durations. Differences in proinflammatory and Treg
      cytokine levels are associated with differences in the resolution of inflammatory
      and noninflammatory pathogen infections.

PMID- 20038537
TI  - Increase in NF-kappaB binding affinity of the variant C allele of the toll-like
      receptor 9 -1237T/C polymorphism is associated with Helicobacter pylori-induced
      gastric disease.
AB  - Colonization of the gastric mucosa by Helicobacter pylori can lead to serious
      clinical outcomes, including gastric cancer. Toll-like receptors (TLRs) play an
      important role in the host response to H. pylori through the recognition of
      pathogen-associated molecular patterns. TLR9, in particular, is partly
      responsible for initiating bacterial induced immunity by binding unmethylated CpG
      DNA, which is abundant in bacteria. A well-documented single nucleotide
      polymorphism (SNP) within the TLR9 promoter (TLR9 -1237T/C), is associated with a
      variety of inflammatory disorders, including allergic asthma, inflammatory bowel
      disease, and atopy. Analysis of the TLR9 promoter gene sequence has shown that
      carriage of the variant "C" allele at position -1237 creates a potential NF
      kappaB binding site that would theoretically increase the transcriptional
      activity of the gene. In this study, we report that the TLR9 -1237 C allele was
      significantly associated with the development of H. pylori-induced premalignant
      gastric changes. Functional analysis of the SNP, supporting the data generated
      from the genetic association study, showed that carriage of the C allele
      increased TLR9 transcriptional activity driven mainly by activation of NF-kappaB.
      Collectively, these findings confirm that the TLR9 -1237T/C polymorphism is a
      risk factor for the development of H. pylori-induced premalignant gastric changes
      and provide a plausible mechanistic explanation.

PMID- 20038539
TI  - Activation of human and chicken toll-like receptors by Campylobacter spp.
AB  - Campylobacter infection in humans is accompanied by severe inflammation of the
      intestinal mucosa, in contrast to colonization of chicken. The basis for the
      differential host response is unknown. Toll-like receptors (TLRs) sense and
      respond to microbes in the body and participate in the induction of an
      inflammatory response. Thus far, the interaction of Campylobacter with chicken
      TLRs has not been studied. Here, we investigated the potential of four
      Campylobacter strains to activate human TLR1/2/6, TLR4, TLR5, and TLR9 and
      chicken TLR2t2/16, TLR4, TLR5, and TLR21. Live bacteria showed no or very limited
      potential to activate TLR2, TLR4, and TLR5 of both the human and chicken species,
      with minor but significant differences between Campylobacter strains. In
      contrast, lysed bacteria induced strong NF-kappaB activation through human
      TLR1/2/6 and TLR4 and chicken TLR2t2/16 and TLR4 but not via TLR5 of either
      species. Interestingly, C. jejuni induced TLR4-mediated beta interferon in human
      but not chicken cells. Furthermore, isolated chromosomal Campylobacter DNA was
      unable to activate human TLR9 in our system, whereas chicken TLR21 was activated
      by DNA from all of the campylobacters tested. Our data are the first comparison
      of TLR-induced immune responses in humans and chickens. The results suggest that
      differences in bacterial cell wall integrity and in TLR responses to
      Campylobacter LOS and/or DNA may contribute to the distinct clinical
      manifestation between the species.

PMID- 20038540
TI  - Lost in translation--basic science in the era of translational research.
AB  - The concept of translational research, which aims to facilitate the application
      of basic scientific discoveries in clinical and community settings, is currently
      in vogue. While there are powerful forces driving this trend, support for
      translational research must be accompanied by a robust investment in basic
      science, which provides the essential raw material for translation and continues
      to represent humanity's best hope to meet a wide range of public health
      challenges.

PMID- 20038538
TI  - Immunization with a combination of three pneumococcal proteins confers additive
      and broad protection against Streptococcus pneumoniae Infections in Mice.
AB  - Pneumococcal polysaccharide-based vaccines are effective in preventing
      pneumococcus infection; however, some drawbacks preclude their widespread use in
      developing and undeveloped countries. Here, we evaluated the protective effects
      of ATP-dependent caseinolytic protease (ClpP), pneumolysin mutant (DeltaA146
      Ply), putative lipoate-protein ligase (Lpl), or combinations thereof against
      pneumococcal infections in mice. Vaccinated mice were intraperitoneally and/or
      intranasally challenged with different pneumococcal strains. In intraperitoneal
      challenge models with pneumococcal strain D39 (serotype 2), the most striking
      protection was obtained with the combination of the three antigens. Similarly,
      with the intranasal challenge models, (i) additive clearance of bacteria in lungs
      was observed for the combination of the three antigens and (ii) a combination
      vaccine conferred complete protection against intranasal infections of three of
      the four most common pneumococcal strains (serotypes 14, 19F, and 23F) and 80%
      protection for pneumococcal strain 6B. Even so, immunity to this combination
      could confer protection against pneumococcal infection with a mixture of four
      serotypes. Our results showed that the combination vaccine was as effective as
      the currently used vaccines (PCV7 and PPV23). These results indicate that system
      immunization with the combination of pneumococcal antigens could provide an
      additive and broad protection against Streptococcus pneumoniae in pneumonia and
      sepsis infection models.

PMID- 20038541
TI  - Family matters: dyadic agreement in end-of-life medical decision making.
AB  - PURPOSE: We examined race/ethnicity and cultural context within hypothetical end
      of-life medical decision scenarios and its influence on patient-proxy agreement.
      DESIGN AND METHODS: Family dyads consisting of an older adult and 1 family
      member, typically an adult child, responded to questions regarding the older
      adult's preferences for cardiopulmonary resuscitation, artificial feeding and
      fluids, and palliative care in hypothetical illness scenarios. The responses of
      34 Caucasian dyads and 30 African American dyads were compared to determine the
      extent to which family members could accurately predict the treatment preferences
      of their older relative. RESULTS: We found higher treatment preference agreement
      among African American dyads compared with Caucasian dyads when considering
      overall raw difference scores (i.e., overtreatment errors can compensate for
      undertreatment errors). Prior advance care planning moderated the effect such
      that lower levels of advance care planning predicted undertreatment errors among
      African American proxies and overtreatment errors among Caucasian proxies. In
      contrast, no racial/ethnic differences in treatment preference agreement were
      found within absolute difference scores (i.e., total error, regardless of the
      direction of error). IMPLICATIONS: This project is one of the first to examine
      the mediators and moderators of dyadic racial/cultural differences in treatment
      preference agreement for end-of-life care in hypothetical illness scenarios.
      Future studies should use mixed method approaches to explore underlying factors
      for racial differences in patient-proxy agreement as a basis for developing
      culturally sensitive interventions to reduce racial disparities in end-of-life
      care options.

PMID- 20038542
TI  - Effects of adaptation on the stimulus selectivity of macaque inferior temporal
      spiking activity and local field potentials.
AB  - Stimulus repetition reduces neural response in cortical areas. Such adaptation is
      used in functional magnetic resonance imaging to infer the selectivity of
      neuronal populations; however, the mechanisms of adaptation remain elusive,
      especially in higher areas. We measured adaptation of spiking activity and local
      field potentials (LFPs) in macaque inferior temporal (IT) cortex for
      parameterized shapes by comparing tuning for test stimuli following a brief
      adaptation with predictions derived from different models of adaptation.
      Adaptation was similar during passive fixation or an attention-demanding task. We
      found consistent adaptation of spiking activity and LFP power in high- (gamma)
      but not low-frequency bands when repeating shapes. Contrary to sharpening models,
      repetition did not affect shape selectivity. The degree of similarity between
      adapter and test shapes was a stronger determinant of adaptation than was the
      response to the adapter. Adaptation still occurred when adapter and test stimuli
      did not spatially overlap, but adaptation was stronger for same, compared with
      different, adapters and test stimulus positions. These adaptation effects were
      similar for spiking and for gamma activity. In conclusion, adaptation of IT
      spiking activity and LFPs in IT is strongly dependent on feature similarities in
      the adapter and test stimuli, in agreement with input, but not firing-rate
      fatigue models.

PMID- 20038543
TI  - BDNF/MAPK/ERK-induced BMP7 expression in the developing cerebral cortex induces
      premature radial glia differentiation and impairs neuronal migration.
AB  - During development of the mammalian nervous system, a combination of genetic and
      environmental factors governs the sequential generation of neurons and glia and
      the initial establishment of the neural circuitry. Here, we demonstrate that
      brain-derived neurotrophic factor (BDNF), one of those local acting factors,
      induces Bone Morphogenetic Protein 7 (BMP7) expression in embryonic neurons by
      activating Mitogen-Activated Protein Kinase/Extracellular signal-Regulated Kinase
      signaling and by the negative regulation of p53/p73 function. We also show that
      intraventricular injection of BMP7 at midgestation induces the early
      differentiation of radial glia into glial precursors and astrocytes and the
      expression of mature glial markers such as the antiadhesive protein SC1. As a
      result of this precocious radial glia maturation, the laminar distribution of
      late-born pyramidal neurons is altered, most likely by the termination of radial
      glia ability to support neuronal migration and the early neuronal detachment from
      the glial rail. We propose a mechanism for BDNF regulation of BMP7 in which local
      activity-driven BDNF-induced BMP7 expression at the end of neurogenesis instructs
      competent precursors to generate astrocytes. Such a mechanism might ensure
      synchronic neuronal and glial maturation at the beginning of cortical activity.

PMID- 20038544
TI  - The effects of COMT (Val108/158Met) and DRD4 (SNP -521) dopamine genotypes on
      brain activations related to valence and magnitude of rewards.
AB  - People's sensitivity to reinforcing stimuli such as monetary gains and losses
      shows a wide interindividual variation that might in part be determined by
      genetic differences. Because of the established role of the dopaminergic system
      in the neural encoding of rewards and negative events, we investigated young
      healthy volunteers being homozygous for either the Valine or Methionine variant
      of the catechol-O-methyltransferase (COMT) codon 158 polymorphism as well as
      homozygous for the C or T variant of the SNP -521 polymorphism of the dopamine D4
      receptor. Participants took part in a gambling paradigm featuring unexpectedly
      high monetary gains and losses in addition to standard gains/losses of expected
      magnitude while undergoing functional magnetic resonance imaging at 3 T. Valence
      related brain activations were seen in the ventral striatum, the anterior
      cingulate cortex, and the inferior parietal cortex. These activations were
      modulated by the COMT polymorphism with greater effects for valine/valine
      participants but not by the D4 receptor polymorphism. By contrast, magnitude
      related effects in the anterior insula and the cingulate cortex were modulated by
      the D4 receptor polymorphism with larger responses for the CC variant. These
      findings emphasize the differential contribution of genetic variants in the
      dopaminergic system to various aspects of reward processing.

PMID- 20038546
TI  - Predictors of intention to quit smoking in Hong Kong secondary school children.
AB  - BACKGROUND: Behavioral theories suggest that a past quit attempt influences
      psycho-social determinants to predict smokers' intention to quit, although no
      study has tested the hypothesis among youth smokers. METHODS: A sample of 1561
      Chinese secondary students, who were current smokers, were collected in a cross
      sectional school-based survey in Hong Kong. RESULTS: For the 943 students with
      past quit attempts, those with lower daily cigarette consumption; who perceived
      smoking would not elicit positive social responses from others; who had one
      parent/teacher who prohibited them to smoke; who were aware of the health hazards
      of smoking and being male smokers, were more likely to have an intention to quit
      smoking. For the 618 students without a past quit attempt, those who did not
      perceive any benefit from smoking; who had parents and teachers to prohibit them
      to smoke and who received social support to quit, were more likely to have an
      intention to quit smoking. CONCLUSION: Strengthening the prohibition of smoking
      and providing social support may help initiate the intention to quit among youth
      smokers without a past quit attempt, while de-normalizing social images of
      smoking, providing information about the health hazards of smoking and relieving
      nicotine addiction may sustain quitting intentions among youth smokers with past
      quit attempts.

PMID- 20038545
TI  - Differential contribution of the supplementary motor area to stabilization of a
      procedural motor skill acquired through different practice schedules.
AB  - Behavioral studies have suggested that the stabilization of motor memory varies
      depending on the practice schedule. The neural substrates underlying this
      schedule-dependent difference in memory stabilization are not known. Here, we
      evaluated the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS)
      applied to different cortical regions and sham after one session of training (Day
      1) of sequential motor skills acquired through blocked (each sequence was
      completely trained before training the next)-practice schedules and random
      (random training of 3 sequences)-practice schedules. The recall of sequences
      learned on Day 1 by Day 2 was measured in different groups of healthy volunteers.
      The rTMS over the supplementary motor area (SMA) but not over control regions or
      over the primary motor cortex (M1) immediately after practice or over SMA 6 h
      later reduced recall relative to sham only in the blocked-practice group. In
      contrast, recall in the random-practice group was unaffected by rTMS. These
      results document a differential contribution of the SMA to the stabilization of
      motor memories acquired through different practice schedules. More generally,
      they indicate that the anatomical substrates underlying motor-memory
      stabilization (or their temporal operation) do differ depending on the practice
      schedule.

PMID- 20038547
TI  - The role of the occupational hygienist in development-oriented public health
      engineering projects.
AB  - Organizations dedicated to applying engineering solutions to improve health in
      developing countries may lack sufficient expertise in the public health aspects
      of these efforts to ensure successful project design and implementation. The
      occupational hygienist is a valuable complement to the efforts needed for
      development-oriented public health engineering projects.

PMID- 20038549
TI  - Intracellular metabolite transporters in plants.
AB  - Due to the presence of plastids, eukaryotic photosynthetic cells represent the
      most highly compartmentalized eukaryotic cells. This high degree of
      compartmentation requires the transport of solutes across intracellular membrane
      systems by specific membrane transporters. In this review, we summarize the
      recent progress on functionally characterized intracellular plant membrane
      transporters and we link transporter functions to Arabidopsis gene identifiers
      and to the transporter classification system. In addition, we outline challenges
      in further elucidating the plant membrane permeome and we provide an outline of
      novel approaches for the functional characterization of membrane transporters.

PMID- 20038548
TI  - FAK mediates the activation of cardiac fibroblasts induced by mechanical stress
      through regulation of the mTOR complex.
AB  - AIMS: Cardiac fibroblasts are activated by mechanical stress, but the underlying
      mechanisms involved remain poorly understood. In this study, we investigated
      whether focal adhesion kinase (FAK) plays a role in the activation of cardiac
      fibroblasts in response to cyclic stretch. METHODS AND RESULTS: Neonatal (NF
      P3/80--third passage, 80% confluence) and adult (AF-P1/80--first passage, 80%
      confluence) rat cardiac fibroblasts were exposed to cyclic stretch (biaxial, 1
      Hz), which enhanced FAK phosphorylation at Tyr397. Proliferation (anti-5-bromo-2'
      deoxyuridine and anti-Ki67 nuclear labelling), differentiation into
      myofibroblasts (expression of alpha-smooth muscle actin--alpha-SMA), and the
      activity of matrix metalloproteinase-2 were equally enhanced in stretched NF
      P3/80 and AF-P1/80. Treatment with the integrin inhibitor RGD peptide impaired
      FAK phosphorylation and increased apoptosis (TUNEL) in non-stretched and
      stretched NF-P3/80, whereas FAK silencing induced by small interfering RNA
      modestly enhanced apoptosis only in stretched cells. RGD peptide or FAK silencing
      suppressed the activation of NF-P3/80 invoked by cyclic stretch. In addition, NF
      P3/80 depleted of FAK were defective in AKT Ser473, TSC-2 Thr1462, and S6 kinase
      Thr389 phosphorylation induced by cyclic stretch. The activation of NF-P3/80
      invoked by cyclic stretch was prevented by pre-treatment with the mammalian
      target of rapamycin (mTOR) inhibitor rapamycin, whereas supplementation with the
      amino acid, leucine, activated S6K and rescued the stretch-induced activation of
      NF-P3/80 depleted of FAK. CONCLUSIONS: These findings demonstrate a critical role
      for the mTOR complex, downstream from FAK, in mediating the activation of cardiac
      fibroblasts in response to mechanical stress.

PMID- 20038550
TI  - Fluorescence intensity decay shape analysis microscopy (FIDSAM) for quantitative
      and sensitive live-cell imaging: a novel technique for fluorescence microscopy of
      endogenously expressed fusion-proteins.
AB  - Fluorescent studies of living plant cells such as confocal microscopy and
      fluorescence lifetime imaging often suffer from a strong autofluorescent
      background contribution that significantly reduces the dynamic image contrast and
      the quantitative access to sub-cellular processes at high spatial resolution.
      Here, we present a novel technique--fluorescence intensity decay shape analysis
      microscopy (FIDSAM)--to enhance the dynamic contrast of a fluorescence image of
      at least one order of magnitude. The method is based on the analysis of the shape
      of the fluorescence intensity decay (fluorescence lifetime curve) and benefits
      from the fact that the decay patterns of typical fluorescence label dyes strongly
      differ from emission decay curves of autofluorescent sample areas. Using FIDSAM,
      we investigated Arabidopsis thaliana hypocotyl cells in their tissue environment,
      which accumulate an eGFP fusion of the plasma membrane marker protein LTI6b
      (LTI6b-eGFP) to low level. Whereas in conventional confocal fluorescence images,
      the membranes of neighboring cells can hardly be optically resolved due to the
      strong autofluorescence of the cell wall, FIDSAM allows for imaging of single,
      isolated membranes at high spatial resolution. Thus, FIDSAM will enable the sub
      cellular analysis of even low-expressed fluorophore-tagged proteins in living
      plant cells. Furthermore, the combination of FIDSAM with fluorescence lifetime
      imaging provides the basis to study the local physico-chemical environment of
      fluorophore-tagged biomolecules in living plant cells.

PMID- 20038555
TI  - Abstracts of the British Geriatrics Society Autumn Meeting. November 8-9, 2009.
      Harrogate, United Kingdom.

PMID- 20038567
TI  - Molecular networks for the study of TCM pharmacology.
AB  - To target complex, multi-factorial diseases more effectively, there has been an
      emerging trend of multi-target drug development based on network biology, as well
      as an increasing interest in traditional Chinese medicine (TCM) that applies a
      more holistic treatment to diseases. Thousands of years' clinic practices in TCM
      have accumulated a considerable number of formulae that exhibit reliable in vivo
      efficacy and safety. However, the molecular mechanisms responsible for their
      therapeutic effectiveness are still unclear. The development of network-based
      systems biology has provided considerable support for the understanding of the
      holistic, complementary and synergic essence of TCM in the context of molecular
      networks. This review introduces available sources and methods that could be
      utilized for the network-based study of TCM pharmacology, proposes a workflow for
      network-based TCM pharmacology study, and presents two case studies on applying
      these sources and methods to understand the mode of action of TCM recipes.

PMID- 20038568
TI  - Simulation of P systems with active membranes on CUDA.
AB  - P systems or Membrane Systems provide a high-level computational modelling
      framework that combines the structure and dynamic aspects of biological systems
      in a relevant and understandable way. They are inherently parallel and non
      deterministic computing devices. In this article, we discuss the motivation,
      design principles and key of the implementation of a simulator for the class of
      recognizer P systems with active membranes running on a (GPU). We compare our
      parallel simulator for GPUs to the simulator developed for a single central
      processing unit (CPU), showing that GPUs are better suited than CPUs to simulate
      P systems due to their highly parallel nature.

PMID- 20038570
TI  - Ghrelin gene products and the regulation of food intake and gut motility.
AB  - A breakthrough using "reverse pharmacology" identified and characterized acyl
      ghrelin from the stomach as the endogenous cognate ligand for the growth hormone
      (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification
      of O-n-octanoylation at serine 3 is the first in peptide discovery history and is
      essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation
      at serine 3, is also produced in the stomach and remains the major molecular form
      secreted into the circulation. The third ghrelin gene product, obestatin, a novel
      23-amino acid peptide identified from rat stomach, was found by comparative
      genomic analysis. Three ghrelin gene products actively participate in modulating
      appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation,
      immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of
      acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits
      in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl
      ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia
      nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver
      cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as
      restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and
      postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase
      (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and
      characterized also from the stomach. To date, ghrelin is the only protein to be
      octanylated, and inhibition of GOAT may have effects only on the stomach and is
      unlikely to affect the synthesis of other proteins. GOAT may provide a critical
      molecular target in developing novel therapeutics for obesity and type 2
      diabetes.

PMID- 20038571
TI  - Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of
      Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells.
AB  - Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major
      constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti
      inflammatory, anticancer and other activities. In this study, our aim was to
      evaluate the antiproliferative activity of these compounds in human hepatoma Hep
      G2 cells and examine the effects of pifithrin-alpha (PFTalpha; a specific p53
      inhibitor) on their apoptotic signaling transduction mechanism. The
      antiproliferative activity was measured by XTT assay. Expression of apoptosis
      related proteins was detected by western blotting. Results showed that at a
      concentration of 30 MUM, the order of antiproliferative activity in Hep G2 cells
      was Cin > Ca > Cal. Cin (IC(50) 9.76 +/- 0.67 MUM) demonstrated an
      antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC(50)
      9.57 +/- 0.61 MUM). Further studies on apoptotic mechanisms of Cin showed that it
      downregulated the expression of Bcl-(XL), upregulated CD95 (APO-1), p53 and Bax
      proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time
      dependent pattern. PFTalpha pre-incubation significantly diminished the effect of
      Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-(XL))
      expression and downregulated the pro-apoptotic (Bax) expression, as well as
      effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in
      Cin-treated cells. This study indicates that Cin was the most potent
      antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2
      cells could be mediated through the p53 induction and CD95 (APO-1) signaling
      pathways.

PMID- 20038569
TI  - Pharmacogenomic discovery using cell-based models.
AB  - Quantitative variation in response to drugs in human populations is
      multifactorial; genetic factors probably contribute to a significant extent.
      Identification of the genetic contribution to drug response typically comes from
      clinical observations and use of classic genetic tools. These clinical studies
      are limited by our inability to control environmental factors in vivo and the
      difficulty of manipulating the in vivo system to evaluate biological changes.
      Recent progress in dissecting genetic contribution to natural variation in drug
      response through the use of cell lines has been made and is the focus of this
      review. A general overview of current cell-based models used in pharmacogenomic
      discovery and validation is included. Discussion includes the current approach to
      translate findings generated from these cell-based models into the clinical arena
      and the use of cell lines for functional studies. Specific emphasis is given to
      recent advances emerging from cell line panels, including the International
      HapMap Project and the NCI60 cell panel. These panels provide a key resource of
      publicly available genotypic, expression, and phenotypic data while allowing
      researchers to generate their own data related to drug treatment to identify
      genetic variation of interest. Interindividual and interpopulation differences
      can be evaluated because human lymphoblastoid cell lines are available from major
      world populations of European, African, Chinese, and Japanese ancestry. The
      primary focus is recent progress in the pharmacogenomic discovery area through ex
      vivo models.

PMID- 20038572
TI  - The effect of a poverty reduction policy and service quality standards on commune
      level primary health care utilization in Thai Nguyen Province, Vietnam.
AB  - Although universal access to quality health services is a primary policy goal of
      the Government of Vietnam (GOVN), economic restructuring and privatization of
      health services have been associated with emerging inequities in access to care.
      A GOVN programme for socio-economic development known as Program 135 (P135)
      designates communes known to be relatively poor as priority localities for
      development resources. Under this programme, basic curative and preventive health
      services, including some prescription drugs, are provided free of charge at
      commune health centres (CHCs). In an effort to improve the quality of care
      provided at CHCs, the national Ministry of Health (MOH) has implemented a set of
      national benchmarks for commune health care, which defines a minimum
      configuration of equipment, staff, training and other elements of service
      provision. This research examines the impact of P135 poverty reduction policy,
      achievement of MOH benchmark indicators and commune socio-economic
      characteristics on CHC utilization rates in Thai Nguyen Province, Vietnam. The
      analysis uses administrative data reported from 178 CHCs in Thai Nguyen Province
      for nine quarters, including 2004, 2005 and the first quarter of 2006. Mixed
      linear regression models are used to estimate the main and interaction effects on
      utilization rates of exposure to the P135 policies, achievement of MOH
      benchmarks, poverty, distance to the district hospital and ethnic composition.
      Communes that are poor and remote have comparatively high CHC utilization rates.
      Multivariate regression results suggest that communes exposed to the P135 policy
      have higher utilization rates, but these effects are conditional upon achievement
      of benchmark standards, thus perceived quality care enhances CHC utilization.
      Combining Program P135 with benchmark investment reduced the gap between primary
      health care utilization in poor communes versus those that are less poor. These
      commune-level findings suggest that CHC policies differentially benefit poor
      communities and reduce inequality in use of health care services.

PMID- 20038573
TI  - Commentary: Tipping the balance: wider waistlines in men but wider inequalities
      in women.

PMID- 20038578
TI  - Stress-induced switch in Numb isoforms enhances Notch-dependent expression of
      subtype-specific transient receptor potential channel.
AB  - The Notch signaling pathway plays an essential role in the regulation of cell
      specification by controlling differentiation, proliferation, and apoptosis. Numb
      is an intrinsic regulator of the Notch pathway and exists in four alternative
      splice variants that differ in the length of their phosphotyrosine-binding domain
      (PTB) and proline-rich region domains. The physiological relevance of the
      existence of the Numb splice variants and their exact regulation are still poorly
      understood. We previously reported that Numb switches from isoforms containing
      the insertion in PTB to isoforms lacking this insertion in neuronal cells
      subjected to trophic factor withdrawal (TFW). The functional relevance of the TFW
      induced switch in Numb isoforms is not known. Here we provide evidence that the
      TFW-induced switch in Numb isoforms regulates Notch signaling strength and Notch
      target gene expression. PC12 cells stably overexpressing Numb isoforms lacking
      the PTB insertion exhibited higher basal Notch activity and Notch-dependent
      transcription of the transient receptor potential channel 6 (TRPC6) when compared
      with those overexpressing Numb isoforms with the PTB insertion. The differential
      regulation of TRPC6 expression is correlated with perturbed calcium signaling and
      increased neuronal vulnerability to TFW-induced death. Pharmacological inhibition
      of the Notch pathway or knockdown of TRPC6 function ameliorates the adverse
      effects caused by the TFW-induced switch in Numb isoforms. Taken together, our
      results indicate that Notch and Numb interaction may influence the sensitivity of
      neuronal cells to injurious stimuli by modulating calcium-dependent apoptotic
      signaling cascades.

PMID- 20038579
TI  - Lysine 63-linked polyubiquitination of TAK1 at lysine 158 is required for tumor
      necrosis factor alpha- and interleukin-1beta-induced IKK/NF-kappaB and JNK/AP-1
      activation.
AB  - Transforming growth factor-beta-activated kinase 1 (TAK1) plays an essential role
      in the tumor necrosis factor alpha (TNFalpha)- and interleukin-1beta (IL-1beta)
      induced IkappaB kinase (IKK)/nuclear factor-kappaB (NF-kappaB) and c-Jun N
      terminal kinase (JNK)/activator protein 1 (AP-1) activation. Here we report that
      TNFalpha and IL-1beta induce Lys(63)-linked TAK1 polyubiquitination at the
      Lys(158) residue within the kinase domain. Tumor necrosis factor receptor
      associated factors 2 and 6 (TRAF2 and -6) act as the ubiquitin E3 ligases to
      mediate Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue in vivo
      and in vitro. Lys(63)-linked TAK1 polyubiquitination at the Lys(158) residue is
      required for TAK1-mediated IKK complex recruitment. Reconstitution of TAK1
      deficient mouse embryo fibroblast cells with TAK1 wild type or a TAK1 mutant
      containing a K158R mutation revealed the importance of this site in TNFalpha and
      IL-1beta-mediated IKK/NF-kappaB and JNK/AP-1 activation as well as IL-6 gene
      expression. Our findings demonstrate that Lys(63)-linked polyubiquitination of
      TAK1 at Lys(158) is essential for its own kinase activation and its ability to
      mediate its downstream signal transduction pathways in response to TNFalpha and
      IL-1beta stimulation.

PMID- 20038580
TI  - Contribution of asparagine residues to the stabilization of a proteinaceous
      antigen-antibody complex, HyHEL-10-hen egg white lysozyme.
AB  - Many germ line antibodies have asparagine residues at specific sites to achieve
      specific antigen recognition. To study the role of asparagine residues in the
      stabilization of antigen-antibody complexes, we examined the interaction between
      hen egg white lysozyme (HEL) and the corresponding HyHEL-10 variable domain
      fragment (Fv). We introduced Ala and Asp substitutions into the Fv side chains of
      L-Asn-31, L-Asn-32, and L-Asn-92, which interact directly with residues in HEL
      via hydrogen bonding in the wild-type Fv-HEL complex, and we investigated the
      interactions between these mutant antibodies and HEL. Isothermal titration
      calorimetric analysis showed that all the mutations decreased the negative
      enthalpy change and decreased the association constants of the interaction.
      Structural analyses showed that the effects of the mutations on the structure of
      the complex could be compensated for by conformational changes and/or by gains in
      other interactions. Consequently, the contribution of two hydrogen bonds was
      minor, and their abolition by mutation resulted in only a slight decrease in the
      affinity of the antibody for its antigen. By comparison, the other two hydrogen
      bonds buried at the interfacial area had large enthalpic advantage, despite
      entropic loss that was perhaps due to stiffening of the interface by the bonds,
      and were crucial to the strength of the interaction. Deletion of these strong
      hydrogen bonds could not be compensated for by other structural changes. Our
      results suggest that asparagine can provide the two functional groups for strong
      hydrogen bond formation, and their contribution to the antigen-antibody
      interaction can be attributed to their limited flexibility and accessibility at
      the complex interface.

PMID- 20038581
TI  - Constitutively active inflammasome in human melanoma cells mediating
      autoinflammation via caspase-1 processing and secretion of interleukin-1beta.
AB  - Interleukin-1beta (IL-1beta) is a pleiotropic cytokine promoting inflammation,
      angiogenesis, and tissue remodeling as well as regulation of immune responses.
      Although IL-1beta contributes to growth and metastatic spread in experimental and
      human cancers, the molecular mechanisms regulating the conversion of the inactive
      IL-1beta precursor to a secreted and active cytokine remains unclear. Here we
      demonstrate that NALP3 inflammasome is constitutively assembled and activated
      with cleavage of caspase-1 in human melanoma cells. Late stage human melanoma
      cells spontaneously secrete active IL-1beta via constitutive activation of the
      NALP3 inflammasome and IL-1 receptor signaling, exhibiting a feature of
      autoinflammatory diseases. Unlike human blood monocytes, these melanoma cells
      require no exogenous stimulation. In contrast, NALP3 functionality in
      intermediate stage melanoma cells requires activation of the IL-1 receptor to
      secrete active IL-1beta; cells from an early stage of melanoma require
      stimulation of the IL-1 receptor plus the co-stimulant muramyl dipeptide. The
      spontaneous secretion of IL-1beta from melanoma cells was reduced by inhibition
      of caspase-1 or the use of small interfering RNA directed against ASC.
      Supernatants from melanoma cell cultures enhanced macrophage chemotaxis and
      promoted in vitro angiogenesis, both prevented by pretreating melanoma cells with
      inhibitors of caspases-1 and -5 or IL-1 receptor blockade. These findings
      implicate IL-1-mediated autoinflammation as contributing to the development and
      progression of human melanoma and suggest that inhibiting the inflammasome
      pathway or reducing IL-1 activity can be a therapeutic option for melanoma
      patients.

PMID- 20038582
TI  - Activation domain-dependent degradation of somatic Wee1 kinase.
AB  - Cell cycle progression is dependent upon coordinate regulation of kinase and
      proteolytic pathways. Inhibitors of cell cycle transitions are degraded to allow
      progression into the subsequent cell cycle phase. For example, the tyrosine
      kinase and Cdk1 inhibitor Wee1 is degraded during G(2) and mitosis to allow
      mitotic progression. Previous studies suggested that the N terminus of Wee1
      directs Wee1 destruction. Using a chemical mutagenesis strategy, we report that
      multiple regions of Wee1 control its destruction. Most notably, we find that the
      activation domain of the Wee1 kinase is also required for its degradation.
      Mutations in this domain inhibit Wee1 degradation in somatic cell extracts and in
      cells without affecting the overall Wee1 structure or kinase activity. More
      broadly, these findings suggest that kinase activation domains may be previously
      unappreciated sites of recognition by the ubiquitin proteasome pathway.

PMID- 20038583
TI  - Map4k4 negatively regulates peroxisome proliferator-activated receptor (PPAR)
      gamma protein translation by suppressing the mammalian target of rapamycin (mTOR)
      signaling pathway in cultured adipocytes.
AB  - The receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is
      considered a master regulator of adipocyte differentiation and promotes glucose
      and lipid metabolism in mature adipocytes. We recently identified the yeast
      Sterile 20 (Ste20) protein kinase ortholog, Map4k4, in an RNA interference-based
      screen as an inhibitor of PPARgamma expression in cultured adipocytes. Here, we
      show that RNA interference-mediated silencing of Map4k4 elevates the levels of
      both PPARgamma1 and PPARgamma2 proteins in 3T3-L1 adipocytes without affecting
      PPARgamma mRNA levels, suggesting that Map4k4 regulates PPARgamma at a post
      transcriptional step. PPARgamma degradation rates are remarkably rapid as
      measured in the presence of cycloheximide (t(1/2) = 2 h), but silencing Map4k4
      had no effect on PPARgamma degradation. However, depletion of Map4k4
      significantly enhances [(35)S]methionine/cysteine incorporation into proteins,
      suggesting that Map4k4 signaling decreases protein translation. We show a
      function of Map4k4 is to inhibit rapamycin-sensitive mammalian target of
      rapamycin (mTOR) activity, decreasing 4E-BP1 phosphorylation. In addition, our
      results show mTOR and 4E-BP1 are required for the increased PPARgamma protein
      expression upon Map4k4 knockdown. Consistent with this concept, adenovirus
      mediated expression of Map4k4 decreased PPARgamma protein levels and mTOR
      phosphorylation. These data show that Map4k4 negatively regulates PPARgamma post
      transcriptionally, by attenuating mTOR signaling and a 4E-BP1-dependent
      mechanism.

PMID- 20038584
TI  - Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2
      (TNFR2).
AB  - Tumor necrosis factor (TNF) elicits its biological activities by stimulation of
      two receptors, TNFR1 and TNFR2, both belonging to the TNF receptor superfamily.
      Whereas TNFR1-mediated signal transduction has been intensively studied and is
      understood in detail, especially with respect to activation of the classical
      NFkappaB pathway, cell death induction, and MAP kinase signaling, TNFR2
      associated signal transduction is poorly defined. Here, we demonstrate in various
      tumor cell lines and primary T-cells that TNFR2, but not TNFR1, induces
      activation of the alternative NFkappaB pathway. In accord with earlier findings
      demonstrating that only membrane TNF, but not soluble TNF, properly activates
      TNFR2, we further show by use of TNFR1- and TNFR2-specific mutants of soluble TNF
      and membrane TNF that soluble ligand trimers fail to activate the alternative
      NFkappaB pathway. In accord with the known inhibitory role of TRAF2 in the
      alternative NFkappaB pathway, TNFR2-, but not TNFR1-specific TNF induced
      depletion of cytosolic TRAF2. Thus, we identified activation of the alternative
      NFkappaB pathway as a TNF signaling effect that can be specifically assigned to
      TNFR2 and membrane TNF.

PMID- 20038585
TI  - Cardiac myosin is a substrate for zipper-interacting protein kinase (ZIPK).
AB  - Zipper-interacting protein kinase (ZIPK) is a member of the death-associated
      protein kinase family associated with apoptosis in nonmuscle cells where it
      phosphorylates myosin regulatory light chain (RLC) to promote membrane blebbing.
      ZIPK mRNA and protein are abundant in heart tissue and isolated ventricular
      neonatal rat cardiac myocytes. An unbiased substrate search performed with
      purified ZIPK on heart homogenates led to the discovery of a prominent 20-kDa
      protein substrate identified as RLC of ventricular myosin. Biochemical analyses
      showed ZIPK phosphorylated cardiac RLC at Ser-15 with a V(max) value 2-fold
      greater than the value for smooth/nonmuscle RLC; cardiac RLC is a favorable
      biochemical substrate. Knockdown of ZIPK in cardiac myocytes by small interfering
      RNA significantly decreased the extent of RLC Ser-15 phosphorylation. Thus, ZIPK
      may act as a cardiac RLC kinase and thereby affect contractility.

PMID- 20038586
TI  - Coproporphyrin excretion and low thiol levels caused by point mutation in the
      Rhodobacter sphaeroides S-adenosylmethionine synthetase gene.
AB  - A spontaneous mutant of Rhodobacter sphaeroides f. sp. denitrificans IL-106 was
      found to excrete a large amount of a red compound identified as coproporphyrin
      III, an intermediate in bacteriochlorophyll and heme synthesis. The mutant, named
      PORF, is able to grow under phototrophic conditions but has low levels of
      intracellular cysteine and glutathione and overexpresses the cysteine synthase
      CysK. The expression of molybdoenzymes such as dimethyl sulfoxide (DMSO) and
      nitrate reductases is also affected under certain growth conditions. Excretion of
      coproporphyrin and overexpression of CysK are not directly related but were both
      found to be consequences of a diminished synthesis of the key metabolite S
      adenosylmethionine (SAM). The wild-type phenotype is restored when the gene metK
      encoding SAM synthetase is supplied in trans. The metK gene in the mutant strain
      has a mutation leading to a single amino acid change (H145Y) in the encoded
      protein. This point mutation is responsible for a 70% decrease in intracellular
      SAM content which probably affects the activities of numerous SAM-dependent
      enzymes such as coproporphyrinogen oxidase (HemN); uroporphyrinogen III
      methyltransferase (CobA), which is involved in siroheme synthesis; and molybdenum
      cofactor biosynthesis protein A (MoaA). We propose a model showing that the
      attenuation of the activities of SAM-dependent enzymes in the mutant could be
      responsible for the coproporphyrin excretion, the low cysteine and glutathione
      contents, and the decrease in DMSO and nitrate reductase activities.

PMID- 20038587
TI  - Roles of RubisCO and the RubisCO-like protein in 5-methylthioadenosine metabolism
      in the Nonsulfur purple bacterium Rhodospirillum rubrum.
AB  - Ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the
      assimilation of atmospheric CO(2) into organic matter and is thus central to the
      existence of life on earth. The beginning of the 2000s was marked by the
      discovery of a new family of proteins, the RubisCO-like proteins (RLPs), which
      are structural homologs of RubisCO. RLPs are unable to catalyze CO(2) fixation.
      The RLPs from Chlorobaculum tepidum, Bacillus subtilis, Geobacillus kaustophilus,
      and Microcystis aeruginosa have been shown to participate in sulfur metabolism.
      Whereas the precise function of C. tepidum RLP is unknown, the B. subtilis, G.
      kaustophilus, and M. aeruginosa RLPs function as tautomerases/enolases in a
      methionine salvage pathway (MSP). Here, we show that the form II RubisCO enzyme
      from the nonsulfur purple bacterium Rhodospirillum rubrum is also able to
      function as an enolase in vivo as part of an MSP, but only under anaerobic
      conditions. However, unlike B. subtilis RLP, R. rubrum RLP does not catalyze the
      enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate. Instead, under aerobic
      growth conditions, R. rubrum RLP employs another intermediate of the MSP, 5
      methylthioribulose-1-phosphate, as a substrate, resulting in the formation of
      different products. To further determine the interrelationship between RubisCOs
      and RLPs (and the potential integration of cellular carbon and sulfur
      metabolism), the functional roles of both RubisCO and RLP have been examined in
      vivo via the use of specific knockout strains and complementation studies of R.
      rubrum. The presence of functional, yet separate, MSPs in R. rubrum under both
      aerobic (chemoheterotrophic) and anaerobic (photoheterotrophic) growth conditions
      has not been observed previously in any organism. Moreover, the aerobic and
      anaerobic sulfur salvage pathways appear to be differentially controlled, with
      novel and previously undescribed steps apparent for sulfur salvage in this
      organism.

PMID- 20038589
TI  - Proteolytic regulation of toxin-antitoxin systems by ClpPC in Staphylococcus
      aureus.
AB  - Bacterial toxin-antitoxin (TA) systems typically consist of a small, labile
      antitoxin that inactivates a specific longer-lived toxin. In Escherichia coli,
      such antitoxins are proteolytically regulated by the ATP-dependent proteases Lon
      and ClpP. Under normal conditions, antitoxin synthesis is sufficient to replace
      this loss from proteolysis, and the bacterium remains protected from the toxin.
      However, if TA production is interrupted, antitoxin levels decrease, and the
      cognate toxin is free to inhibit the specific cellular component, such as mRNA,
      DnaB, or gyrase. To date, antitoxin degradation has been studied only in E. coli,
      so it remains unclear whether similar mechanisms of regulation exist in other
      organisms. To address this, we followed antitoxin levels over time for the three
      known TA systems of the major human pathogen Staphylococcus aureus, mazEF, axe1
      txe1, and axe2-txe2. We observed that the antitoxins of these systems, MazE(sa),
      Axe1, and Axe2, respectively, were all degraded rapidly (half-life [t(1/2)],
      approximately 18 min) at rates notably higher than those of their E. coli
      counterparts, such as MazE (t(1/2), approximately 30 to 60 min). Furthermore,
      when S. aureus strains deficient for various proteolytic systems were examined
      for changes in the half-lives of these antitoxins, only strains with clpC or clpP
      deletions showed increased stability of the molecules. From these studies, we
      concluded that ClpPC serves as the functional unit for the degradation of all
      known antitoxins in S. aureus.

PMID- 20038588
TI  - ClpP of Streptococcus mutans differentially regulates expression of genomic
      islands, mutacin production, and antibiotic tolerance.
AB  - Streptococcus mutans is the primary etiological agent of human dental caries and,
      at times, of infective endocarditis. Within the oral cavity, the pathogen is
      subjected to conditions of stress. A well-conserved protein complex named ClpP
      (caseinolytic protease) plays a vital role in adaptation under stress conditions.
      To gain a better understanding of the global role of the ClpP protease in
      cellular homeostasis, a transcriptome analysis was performed using a DeltaclpP
      mutant strain. The expression levels of more than 100 genes were up- or
      downregulated in the DeltaclpP mutant compared to the wild type. Notably, the
      expression of genes in several genomic islands, such as TnSmu1 and TnSmu2, was
      differentially modulated in the DeltaclpP mutant strain. ClpP deficiency also
      increased the expression of genes associated with a putative CRISPR locus.
      Furthermore, several stress-related genes and genes encoding bacteriocin-related
      peptides and many transcription factors were also found to be altered in the
      DeltaclpP mutant strain. A comparative analysis of the two-dimensional protein
      profile of the wild type and the DeltaclpP mutant strains showed altered protein
      profiles. Comparison of the transcriptome data with the proteomic data identified
      four common gene products, suggesting that the observed altered protein
      expression of these genes could be due to altered transcription. The results
      presented here indicate that ClpP-mediated proteolysis plays an important global
      role in the regulation of several important traits in this pathogen.

PMID- 20038590
TI  - Flavobacterium johnsoniae gldN and gldO are partially redundant genes required
      for gliding motility and surface localization of SprB.
AB  - Cells of the gliding bacterium Flavobacterium johnsoniae move rapidly over
      surfaces. Mutations in gldN cause a partial defect in gliding. A novel
      bacteriophage selection strategy was used to aid construction of a strain with a
      deletion spanning gldN and the closely related gene gldO in an otherwise wild
      type F. johnsoniae UW101 background. Bacteriophage transduction was used to move
      a gldN mutation into F. johnsoniae UW101 to allow phenotypic comparison with the
      gldNO deletion mutant. Cells of the gldN mutant formed nonspreading colonies on
      agar but retained some ability to glide in wet mounts. In contrast, cells of the
      gldNO deletion mutant were completely nonmotile, indicating that cells require
      GldN, or the GldN-like protein GldO, to glide. Recent results suggest that
      Porphyromonas gingivalis PorN, which is similar in sequence to GldN, has a role
      in protein secretion across the outer membrane. Cells of the F. johnsoniae gldNO
      deletion mutant were defective in localization of the motility protein SprB to
      the cell surface, suggesting that GldN may be involved in secretion of components
      of the motility machinery. Cells of the gldNO deletion mutant were also deficient
      in chitin utilization and were resistant to infection by bacteriophages,
      phenotypes that may also be related to defects in protein secretion.

PMID- 20038591
TI  - The Streptococcus mutans IrvR repressor is a CI-like regulator that functions
      through autocleavage and Clp-dependent proteolysis.
AB  - Previous work has shown that irvR is required for the proper regulation of
      genetic competence and dextran-dependent aggregation due to its ability to
      repress the transcription regulator irvA. In this study, we determined the
      mechanism used to relieve the repression of irvA. We demonstrate that IrvR is a
      "LexA-like" protein with four conserved amino acid residues likely required for
      IrvR autocleavage activity. Furthermore, recombinant IrvR protein purified from
      Escherichia coli was competent to undergo autocleavage in vitro. Using several
      truncated IrvR constructs, we show that the amino acids adjacent to the
      autocleavage site are essential for relieving irvA repression and engaging the
      irvA-dependent regulatory pathway primarily through the ClpXP and ClpCP
      proteases. By extending the IrvR C terminus with an epitope derived from the
      autocleavage site, we were also able to create a constitutive Clp-dependent
      degradation of the full-length IrvR protein. This suggests that the derepression
      of irvA occurs through a two-step mechanism involving the initial autocleavage of
      IrvR and exposure of a proteolytic degradation sequence followed by Clp-dependent
      degradation of the IrvR DNA binding domain. Thus, irvA derepression is highly
      analogous to the genetic switch mechanism used to regulate lysogeny in
      bacteriophages.

PMID- 20038592
TI  - Coordinated regulation of 23S rRNA maturation in Escherichia coli.
AB  - In Escherichia coli, rRNAs are transcribed as precursors and require processing
      at the 3' and 5' ends to generate mature RNA molecules. The largest of these
      RNAs, 23S rRNA, is matured at the 3' end by a set of exonucleases and at the 5'
      end by an unknown RNase. Whether the 3' and 5' maturation steps occur
      independently or are coupled has previously been unclear. By assessing the levels
      of precursors accumulating at the 3' and 5' ends, we provide evidence that these
      processes may be linked. Thus, each of several conditions that led to precursor
      accumulation at one end also did so at the other end. We also observed that each
      end undergoes maturation at similar rates, suggesting that the two processes
      could be coupled. Finally, we provide evidence that processing at the 3' end
      facilitates 5'-end maturation. A model to explain the basis for the observed
      directionality of the reactions is proposed. This information will aid in the
      search for the enzyme responsible for final maturation of the 5' end of 23S rRNA.

PMID- 20038593
TI  - Sequence motifs and proteolytic cleavage of the collagen-like glycoprotein BclA
      required for its attachment to the exosporium of Bacillus anthracis.
AB  - Bacillus anthracis spores are enclosed by an exosporium comprised of a basal
      layer and an external hair-like nap. The filaments of the nap are composed of
      trimers of the collagen-like glycoprotein BclA. The attachment of essentially all
      BclA trimers to the exosporium requires the basal layer protein BxpB, and both
      proteins are included in stable high-molecular-mass exosporium complexes. BclA
      contains a proteolytically processed 38-residue amino-terminal domain (NTD) that
      is essential for basal-layer attachment. In this report, we identify three NTD
      submotifs (SM1a, SM1b, and SM2, located within residues 21 to 33) that are
      important for BclA attachment and demonstrate that residue A20, the amino
      terminal residue of processed BclA, is not required for attachment. We show that
      the shortest NTD of BclA-or of a recombinant protein-sufficient for high-level
      basal-layer attachment is a 10-residue motif consisting of an initiating
      methionine, an apparently arbitrary second residue, SM1a or SM1b, and SM2. We
      also demonstrate that cleavage of the BclA NTD is necessary for efficient
      attachment to the basal layer and that the site of cleavage is somewhat flexible,
      at least in certain mutant NTDs. Finally, we propose a mechanism for BclA
      attachment and discuss the possibility that analogous mechanisms are involved in
      the attachment of many different collagen-like proteins of B. anthracis and
      closely related Bacillus species.

PMID- 20038594
TI  - Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C
      heterotrimer.
AB  - RND (resistance-nodulation-division) family transporters in Gram-negative
      bacteria frequently pump out a wide range of inhibitors and often contribute to
      multidrug resistance to antibiotics and biocides. An archetypal RND pump of
      Escherichia coli, AcrB, is known to exist as a homotrimer, and this construction
      is essential for drug pumping through the functionally rotating mechanism. MdtBC,
      however, appears different because two pump genes coexist within a single operon,
      and genetic deletion data suggest that both pumps must be expressed in order for
      the drug efflux to occur. We have expressed the corresponding genes, with one of
      them in a His-tagged form. Copurification of MdtB and MdtC under these conditions
      showed that they form a complex, with an average stoichiometry of 2:1.
      Unequivocal evidence that only the trimer containing two B protomers and one C
      protomer is active was obtained by expressing all possible combinations of B and
      C in covalently linked forms. Finally, conversion into alanine of the residues,
      known to form a proton translocation pathway in AcrB, inactivated transport only
      when made in MdtB, not when made in MdtC, a result suggesting that MdtC plays a
      different role not directly involved in drug binding and extrusion.

PMID- 20038597
TI  - Thymic development beyond beta-selection requires phosphatidylinositol 3-kinase
      activation by CXCR4.
AB  - T cell development requires phosphatidylinositol 3-kinase (PI3K) signaling with
      contributions from both the class IA, p110delta, and class IB, p110gamma
      catalytic subunits. However, the receptors on immature T cells by which each of
      these PI3Ks are activated have not been identified, nor has the mechanism behind
      their functional redundancy in the thymus. Here, we show that PI3K signaling from
      the preTCR requires p110delta, but not p110gamma. Mice deficient for the class IB
      regulatory subunit p101 demonstrated the requirement for p101 in T cell
      development, implicating G protein-coupled receptor signaling in beta-selection.
      We found evidence of a role for CXCR4 using small molecule antagonists in an in
      vitro model of beta-selection and demonstrated a requirement for CXCR4 during
      thymic development in CXCR4-deficient embryos. Finally, we demonstrate that
      CXCL12, the ligand for CXCR4, allows for Notch-dependent differentiation of DN3
      thymocytes in the absence of supporting stromal cells. These findings establish a
      role for CXCR4-mediated PI3K signaling that, together with signals from Notch and
      the preTCR, contributes to continued T cell development beyond beta-selection.

PMID- 20038598
TI  - Decoration of T-independent antigen with ligands for CD22 and Siglec-G can
      suppress immunity and induce B cell tolerance in vivo.
AB  - Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues
      are normally regulated by induction of anergy or apoptosis. According to the "two
      signal" model, antigen recognition alone should render B cells tolerant unless T
      cell help or inflammatory signals such as lipopolysaccharide are provided.
      However, no such signals seem necessary for responses to T-independent type 2 (TI
      2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like
      receptor ligands. How then do mature B cells avoid making a TI-2-like response to
      multimeric self-antigens? We present evidence that TI-2 antigens decorated with
      ligands of inhibitory sialic acid-binding Ig-like lectins (siglecs) are poorly
      immunogenic and can induce tolerance to subsequent challenge with immunogenic
      antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction,
      preventing plasma cell differentiation or survival. Although mutations in CD22
      and its signaling machinery have been associated with dysregulated B cell
      development and autoantibody production, previous analyses failed to identify a
      tolerance defect in antigen-specific mutant B cells. Our results support a role
      for siglecs in B cell self-/nonself-discrimination, namely suppressing responses
      to self-associated antigens while permitting rapid "missing self"-responses to
      unsialylated multimeric antigens. The results suggest use of siglec ligand
      antigen constructs as an approach for inducing tolerance.

PMID- 20038599
TI  - The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T
      cells.
AB  - The cytidine deaminase APOBEC3G (A3G) enzyme exerts an intrinsic anti-human
      immunodeficiency virus (HIV) defense by introducing lethal G-to-A hypermutations
      in the viral genome. The HIV-1 viral infectivity factor (Vif) protein triggers
      degradation of A3G and counteracts this antiviral effect. The impact of A3G on
      the adaptive cellular immune response has not been characterized. We examined
      whether A3G-edited defective viruses, which are known to express truncated or
      misfolded viral proteins, activate HIV-1-specific (HS) CD8+ cytotoxic T
      lymphocytes (CTLs). To this end, we compared the immunogenicity of cells infected
      with wild-type or Vif-deleted viruses in the presence or absence of the cytidine
      deaminase. The inhibitory effect of A3G on HIV replication was associated with a
      strong activation of cocultivated HS-CTLs. CTL activation was particularly marked
      with Vif-deleted HIV and with viruses harboring A3G. Enzymatically inactive A3G
      mutants failed to enhance CTL activation. We also engineered proviruses bearing
      premature stop codons in their genome as scars of A3G editing. These viruses were
      not infectious but potently activated HS-CTLs. Therefore, the pool of defective
      viruses generated by A3G represents an underestimated source of viral antigens.
      Our results reveal a novel function for A3G, acting not only as an intrinsic
      antiviral factor but also as an inducer of the adaptive immune system.

PMID- 20038600
TI  - CD207+ CD103+ dermal dendritic cells cross-present keratinocyte-derived antigens
      irrespective of the presence of Langerhans cells.
AB  - Recent studies have challenged the view that Langerhans cells (LCs) constitute
      the exclusive antigen-presenting cells of the skin and suggest that the dermal
      dendritic cell (DDC) network is exceedingly complex. Using knockin mice to track
      and ablate DCs expressing langerin (CD207), we discovered that the dermis
      contains five distinct DC subsets and identified their migratory counterparts in
      draining lymph nodes. Based on this refined classification, we demonstrated that
      the quantitatively minor CD207+ CD103+ DDC subset is endowed with the unique
      capability of cross-presenting antigens expressed by keratinocytes irrespective
      of the presence of LCs. We further showed that Y-Ae, an antibody that is widely
      used to monitor the formation of complexes involving I-Ab molecules and a peptide
      derived from the I-E alpha chain, recognizes mature skin DCs that express I-Ab
      molecules in the absence of I-E alpha. Knowledge of this extra reactivity is
      important because it could be, and already has been, mistakenly interpreted to
      support the view that antigen transfer can occur between LCs and DDCs.
      Collectively, these data revisit the transfer of antigen that occurs between
      keratinocytes and the five distinguishable skin DC subsets and stress the high
      degree of functional specialization that exists among them.

PMID- 20038601
TI  - Negative regulation of autoimmune demyelination by the inhibitory receptor CLM-1.
AB  - Multiple sclerosis and its preclinical model, experimental autoimmune
      encephalomyelitis, are marked by perivascular inflammation and demyelination.
      Myeloid cells, derived from circulating progenitors, are a prominent component of
      the inflammatory infiltrate and are believed to directly contribute to
      demyelination and axonal damage. How the cytotoxic activity of these myeloid
      cells is regulated is poorly understood. We identify CMRF-35-like molecule-1 (CLM
      1) as a negative regulator of autoimmune demyelination. CLM-1 is expressed on
      inflammatory myeloid cells present in demyelinating areas of the spinal cord
      after immunization of mice with MOG35-55 (myelin oligodendrocyte glycoprotein)
      peptide. Absence of CLM-1 resulted in significantly increased nitric oxide and
      proinflammatory cytokine production, along with increased demyelination and
      worsened clinical scores, whereas T cell responses in the periphery or in the
      spinal cord remained unaffected. This study thus identifies CLM-1 as a negative
      regulator of myeloid effector cells in autoimmune demyelination.

PMID- 20038602
TI  - Generation of PLZF+ CD4+ T cells via MHC class II-dependent thymocyte-thymocyte
      interaction is a physiological process in humans.
AB  - Human thymocytes, unlike mouse thymocytes, express major histocompatibility
      complex (MHC) class II molecules on their surface, especially during the fetal
      and perinatal stages. Based on this observation, we previously identified a novel
      developmental pathway for the generation of CD4+ T cells via interactions between
      MHC class II-expressing thymocytes (thymocyte-thymocyte [T-T] interactions) with
      a transgenic mouse system. However, the developmental dissection of this T-T
      interaction in humans has not been possible because of the lack of known cellular
      molecules specific for T-T CD4+ T cells. We show that promyelocytic leukemia zinc
      finger protein (PLZF) is a useful marker for the identification of T-T CD4+ T
      cells. With this analysis, we determined that a substantial number of fetal
      thymocytes and splenocytes express PLZF and acquire innate characteristics during
      their development in humans. Although these characteristics are quite similar to
      invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have
      a diverse T cell receptor repertoire and are restricted by MHC class II
      molecules. These findings define a novel human CD4+ T cell subset that develops
      via an MHC class II-dependent T-T interaction.

PMID- 20038603
TI  - Essential role of mannose-binding lectin-associated serine protease-1 in
      activation of the complement factor D.
AB  - The complement system is an essential component of innate immunity, participating
      in the pathogenesis of inflammatory diseases and in host defense. In the lectin
      complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition
      molecules, and MBL-associated serine protease (MASP) is a key enzyme; MASP-2 is
      responsible for the lectin pathway activation. The function of other serine
      proteases (MASP-1 and MASP-3) is still obscure. In this study, we generated a
      MASP-1- and MASP-3-deficient mouse model (Masp1/3-/-) and found that no
      activation of the alternative pathway was observed in Masp1/3-/- serum. Mass
      spectrometric analysis revealed that circulating complement factor D (Df) in
      Masp1/3-/- mice is a zymogen (pro-Df) with the activation peptide QPRGR at its N
      terminus. These results suggested that Masp1/3-/- mice failed to convert pro-Df
      to its active form, whereas it was generally accepted that the activation peptide
      of pro-Df is removed during its secretion and factor D constitutively exists in
      an active form in the circulation. Furthermore, recombinant MASP-1 converted pro
      Df to the active form in vitro, although the activation mechanism of pro-Df by
      MASP-1 is still unclear. Thus, it is clear that MASP-1 is an essential protease
      of both the lectin and alternative complement pathways.

PMID- 20038604
TI  - The nonpolymorphic MHC Qa-1b mediates CD8+ T cell surveillance of antigen
      processing defects.
AB  - The nonclassical major histocompatibility complex (MHC) Qa-1b accommodates
      monomorphic leader peptides and functions as a ligand for germ line receptors
      CD94/NKG2, which are expressed by natural killer cells and CD8+ T cells. We here
      describe that the conserved peptides are replaced by a novel peptide repertoire
      of surprising diversity as a result of impairments in the antigen-processing
      pathway. This novel peptide repertoire represents immunogenic neoantigens for
      CD8+ T cells, as we found that these Qa-1b-restricted T cells dominantly
      participated in the response to tumors with processing deficiencies. A
      surprisingly wide spectrum of target cells, irrespective of transformation
      status, MHC background, or type of processing deficiency, was recognized by this
      T cell subset, complying with the conserved nature of Qa-1b. Target cell
      recognition depended on T cell receptor and Qa-1b interaction, and immunization
      with identified peptide epitopes demonstrated in vivo priming of CD8+ T cells.
      Our data reveal that Qa-1b, and most likely its human homologue human leukocyte
      antigen-E, is important for the defense against processing-deficient cells by
      displacing the monomorphic leader peptides, which relieves the inhibition through
      CD94/NKG2A on lymphocytes, and by presenting a novel repertoire of immunogenic
      peptides, which recruits a subset of cytotoxic CD8+ T cells.

PMID- 20038605
TI  - Yeast cell adhesion molecules have functional amyloid-forming sequences.
AB  - The occurrence of highly conserved amyloid-forming sequences in Candida albicans
      Als proteins (H. N. Otoo et al., Eukaryot. Cell 7:776-782, 2008) led us to search
      for similar sequences in other adhesins from C. albicans and Saccharomyces
      cerevisiae. The beta-aggregation predictor TANGO found highly beta-aggregation
      prone sequences in almost all yeast adhesins. These sequences had an unusual
      amino acid composition: 77% of their residues were beta-branched aliphatic amino
      acids Ile, Thr, and Val, which is more than 4-fold greater than their prevalence
      in the S. cerevisiae proteome. High beta-aggregation potential peptides from S.
      cerevisiae Flo1p and C. albicans Eap1p rapidly formed insoluble amyloids, as
      determined by Congo red absorbance, thioflavin T fluorescence, and fiber
      morphology. As examples of the amyloid-forming ability of the native proteins,
      soluble glycosylphosphatidylinositol (GPI)-less fragments of C. albicans Als5p
      and S. cerevisiae Muc1p also formed amyloids within a few days under native
      conditions at nM concentrations. There was also evidence of amyloid formation in
      vivo: the surfaces of cells expressing wall-bound Als1p, Als5p, Muc1p, or Flo1p
      were birefringent and bound the fluorescent amyloid-reporting dye thioflavin T.
      Both of these properties increased upon aggregation of the cells. In addition,
      amyloid binding dyes strongly inhibited aggregation and flocculation. The results
      imply that amyloid formation is an intrinsic property of yeast cell adhesion
      proteins from many gene families and that amyloid formation is an important
      component of cellular aggregation mediated by these proteins.

PMID- 20038606
TI  - Aspergillus fumigatus survival in alkaline and extreme zinc-limiting environments
      relies on the induction of a zinc homeostasis system encoded by the zrfC and
      aspf2 genes.
AB  - Aspergillus fumigatus has three zinc transporter-encoding genes whose expression
      is regulated by both pH and the environmental concentration of zinc. We have
      previously reported that the zrfA and zrfB genes of A. fumigatus are transcribed
      at higher levels and are required for fungal growth under acidic zinc-limiting
      conditions whereas they are dispensable for growth in neutral or alkaline zinc
      limiting media. Here we report that the transporter of the zinc uptake system
      that functions in A. fumigatus growing in neutral or alkaline environments is
      encoded by zrfC. The transcription of zrfC occurs divergently with respect to the
      adjacent aspf2 gene, which encodes an immunodominant antigen secreted by A.
      fumigatus. The two genes-zrfC and aspf2-are required to different extents for
      fungal growth in alkaline and extreme zinc-limiting media. Indeed, these
      environmental conditions induce the simultaneous transcription of both genes
      mediated by the transcriptional regulators ZafA and PacC. ZafA upregulates the
      expression of zrfC and aspf2 under zinc-limiting conditions regardless of the
      ambient pH, whereas PacC represses the expression of these genes under acidic
      growth conditions. Interestingly, the mode of action of PacC for zrfC-aspf2
      transcription contrasts with the more widely accepted model for PacC function,
      according to which under alkaline growth conditions PacC would activate the
      transcription of alkaline-expressed genes but would repress the transcription of
      acid-expressed genes. In sum, this report provides a good framework for
      investigating several important aspects of the biology of species of Aspergillus,
      including the repression of alkaline genes by PacC at acidic pH and the
      interrelationship that must exist between tissue pH, metal availability in the
      host tissue, and fungal virulence.

PMID- 20038607
TI  - Global gene expression analysis during sporulation of the aquatic fungus
      Blastocladiella emersonii.
AB  - The Blastocladiella emersonii life cycle presents a number of drastic biochemical
      and morphological changes, mainly during two cell differentiation stages:
      germination and sporulation. To investigate the transcriptional changes taking
      place during the sporulation phase, which culminates with the production of the
      zoospores, motile cells responsible for the dispersal of the fungus, microarray
      experiments were performed. Among the 3,773 distinct genes investigated, a total
      of 1,207 were classified as differentially expressed, relative to time zero of
      sporulation, at at least one of the time points analyzed. These results indicate
      that accurate transcriptional control takes place during sporulation, as well as
      indicating the necessity for distinct molecular functions throughout this
      differentiation process. The main functional categories overrepresented among
      upregulated genes were those involving the microtubule, the cytoskeleton, signal
      transduction involving Ca(2+), and chromosome organization. On the other hand,
      protein biosynthesis, central carbon metabolism, and protein degradation were the
      most represented functional categories among downregulated genes. Gene expression
      changes were also analyzed in cells sporulating in the presence of subinhibitory
      concentrations of glucose or tryptophan. Data obtained revealed overexpression of
      microtubule and cytoskeleton transcripts in the presence of glucose, probably
      causing the shape and motility problems observed in the zoospores produced under
      this condition. In contrast, the presence of tryptophan during sporulation led to
      upregulation of genes involved in oxidative stress, proteolysis, and protein
      folding. These results indicate that distinct physiological pathways are involved
      in the inhibition of sporulation due to these two classes of nutrient sources.

PMID- 20038608
TI  - RNA polymerase I transcription silences noncoding RNAs at the ribosomal DNA locus
      in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae the repeated units of the ribosomal locus,
      transcribed by RNA polymerase I (Pol I), are interrupted by nontranscribed
      spacers (NTSs). These NTS regions are transcribed by RNA polymerase III to
      synthesize 5S RNA and by RNA polymerase II (Pol II) to synthesize, at low levels,
      noncoding RNAs (ncRNAs). While transcription of both RNA polymerase I and III is
      highly characterized, at the ribosomal DNA (rDNA) locus only a few studies have
      been performed on Pol II, whose repression correlates with the SIR2-dependent
      silencing. The involvement of both chromatin organization and Pol I transcription
      has been proposed, and peculiar chromatin structures might justify "ribosomal"
      Pol II silencing. Reporter genes inserted within the rDNA units have been
      employed for these studies. We studied, in the natural context, yeast mutants
      differing in Pol I transcription in order to find whether correlations exist
      between Pol I transcription and Pol II ncRNA production. Here, we demonstrate
      that silencing at the rDNA locus represses ncRNAs with a strength inversely
      proportional to Pol I transcription. Moreover, localized regions of histone
      hyperacetylation appear in cryptic promoter elements when Pol II is active and in
      the coding region when Pol I is functional; in addition, DNA topoisomerase I site
      specific activity follows RNA polymerase I transcription. The repression of
      ncRNAs at the rDNA locus, in response to RNA polymerase I transcription, could
      represent a physiological circuit control whose mechanism involves modification
      of histone acetylation.

PMID- 20038609
TI  - Comparison of methods for profiling O-glycosylation: Human Proteome Organisation
      Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1.
AB  - The Human Proteome Organisation Human Disease Glycomics/Proteome Initiative
      recently coordinated a multi-institutional study that evaluated methodologies
      that are widely used for defining the N-glycan content in glycoproteins. The
      study convincingly endorsed mass spectrometry as the technique of choice for
      glycomic profiling in the discovery phase of diagnostic research. The present
      study reports the extension of the Human Disease Glycomics/Proteome Initiative's
      activities to an assessment of the methodologies currently used for O-glycan
      analysis. Three samples of IgA1 isolated from the serum of patients with multiple
      myeloma were distributed to 15 laboratories worldwide for O-glycomics analysis. A
      variety of mass spectrometric and chromatographic procedures representative of
      current methodologies were used. Similar to the previous N-glycan study, the
      results convincingly confirmed the pre-eminent performance of MS for O-glycan
      profiling. Two general strategies were found to give the most reliable data,
      namely direct MS analysis of mixtures of permethylated reduced glycans in the
      positive ion mode and analysis of native reduced glycans in the negative ion mode
      using LC-MS approaches. In addition, mass spectrometric methodologies to analyze
      O-glycopeptides were also successful.

PMID- 20038610
TI  - Role for the regulator of G-protein signaling homology domain of G protein
      coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and rhodopsin
      phosphorylation.
AB  - Phosphorylation of G protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) is
      a major mechanism of desensitization of these receptors. GPCR activation of GRKs
      involves an allosteric site on GRKs distinct from the catalytic site. Although
      recent studies have suggested an important role of the N- and C-termini and
      domains surrounding the kinase active site in allosteric activation, the nature
      of that site and the relative roles of the RH domain in particular remain
      unknown. Based on evolutionary trace analysis of both the RH and kinase domains
      of the GRK family, we identified an important cluster encompassing helices 3, 9,
      and 10 in the RH domain in addition to sites in the kinase domain. To define its
      function, a panel of GRK5 and -6 mutants was generated and screened by intact
      cell assay of constitutive GRK phosphorylation of the beta(2)-adrenergic receptor
      (beta 2AR), in vitro GRK phosphorylation of light-activated rhodopsin, and basal
      catalytic activity measured by tubulin phosphorylation and autophosphorylation. A
      number of double mutations within helices 3, 9, and 10 reduced phosphorylation of
      the beta2AR and rhodopsin by 50 to 90% relative to wild-type GRK, as well as
      autophosphorylation and tubulin phosphorylation. Based on these results, helix 9
      peptide mimetics were designed, and several were found to inhibit rhodopsin
      phosphorylation by GRK5 with an IC(50) of approximately 30 microM. In summary,
      our studies have uncovered previously unrecognized functionally important sites
      in the regulator of G-protein signaling homology domain of GRK5 and -6 and
      identified a peptide inhibitor with potential for specific blockade of GRK
      mediated phosphorylation of receptors.

PMID- 20038611
TI  - The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in
      acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo
      interactions with established drugs.
AB  - Antiapoptotic Bcl-2 proteins are overexpressed in a number of cancers, including
      leukemias, and are frequently associated with resistance to conventional
      chemotherapeutic drugs. ABT-737, a Bcl-2 homology domain 3 mimetic (for
      structure, see Nature 435:677-681, 2005) inhibits the prosurvival function of Bcl
      2, Bcl-X(L), and Bcl-w. We show that ABT-737 was effective as a single agent
      against a panel of pediatric acute lymphoblastic leukemia (ALL) xenografts,
      previously established, from patient biopsies, in immunodeficient mice. Although
      in vitro resistance of leukemia cell lines correlated with expression of the
      prosurvival protein Mcl-1, there was no relationship between Mcl-1 expression and
      in vivo xenograft response to ABT-737. However, expression of the pro-apoptotic
      protein Bim, and the extent of its association with Bcl-2, significantly
      correlated with in vivo ABT-737 sensitivity. ABT-737 potentiated the antileukemic
      effects of L-asparaginase, topotecan, vincristine, and etoposide against drug
      resistant xenografts in vitro and in vivo. Finally, we show that the combination
      of L-asparaginase (by specifically down-regulating Mcl-1 protein levels),
      topotecan (by activating p53 via DNA damage), and ABT-737 (by inhibiting
      antiapoptotic Bcl-2 family members) caused profound synergistic antileukemic
      efficacy both in vitro and in vivo. Rational targeting of specific components of
      the apoptotic pathway may be a useful approach to improve the treatment of
      refractory or relapsed pediatric ALL. Overall, this study supports the inclusion
      of the clinical derivative of ABT-737, ABT-263 (for structure, see Cancer Res
      68:3421-3428, 2008), into clinical trials against relapsed/refractory pediatric
      ALL.

PMID- 20038612
TI  - Clinical pharmacokinetics of oral controlled-release 5-fluorocytosine.
AB  - 5-Fluorocytosine (5FC) is an oral antifungal that is currently used in
      combination with amphotericin B to treat Cryptococcus neoformans
      meningoencephalitis. The oral dosing of 5FC could be optimized by the use of a
      controlled-release (CR) formulation. The objective of the current study was to
      develop two prototype 5FC-CR formulations and evaluate the single-dose (1,500-mg)
      serum pharmacokinetic profiles of those formulations relative to the profile of
      the commercially available, immediate-release 5FC product (Ancobon) by the use of
      a phase 1, open-label, randomized, three-phase, crossover pharmacokinetic study
      design. Hydroxypropyl methylcellulose was utilized as the rate-controlling matrix
      to compound the 5FC-CR tablets. The two prototype 5FC-CR formulations
      demonstrated 80% release at 13.0 and 18.4 h, respectively, whereas the immediate
      release product demonstrated 80% release at 0.28 h, as determined in vitro by the
      United States Pharmacopeia apparatus 2 dissolution method. Five subjects
      completed all three phases of the study without any adverse events. The mean
      maximum concentration, the area under the curve from time zero to 24 h, and the
      area under the curve from time zero to infinity were approximately 50% lower (P <
      0.01) with the 5FC-CR formulations than with the immediate-release 5FC product.
      However, no statistically significant differences in the minimum concentrations
      at 24 h were noted between the formulations. The gastric absorption profile of
      5FC-CR was well predicted by in vitro dissolution. Future exploration of a
      gastroretentive 5FC-CR formulation could overcome the marked lack of
      bioequivalence observed in the present study.

PMID- 20038613
TI  - Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata
      bloodstream isolates serially obtained from a hematopoietic stem cell transplant
      recipient.
AB  - We describe the acquisition of flucytosine, azole, and caspofungin resistance in
      sequential Candida glabrata bloodstream isolates collected from a bone marrow
      transplant patient with clinical failure. Point mutations in C. glabrata FUR1
      (CgFUR1) and CgFKS2 and overexpression of CgCDR1 and CgCDR2 were observed in
      resistant isolates.

PMID- 20038614
TI  - Clinical pharmacodynamics of cefepime in patients infected with Pseudomonas
      aeruginosa.
AB  - We evaluated cefepime exposures in patients infected with Pseudomonas aeruginosa
      to identify the pharmacodynamic relationship predictive of microbiological
      response. Patients with non-urinary tract P. aeruginosa infections and treated
      with cefepime were included. Free cefepime exposures were estimated by using a
      validated population pharmacokinetic model. P. aeruginosa MICs were determined by
      Etest and pharmacodynamic indices (the percentage of the dosing interval that the
      free drug concentration remains above the MIC of the infecting organism [fT >
      MIC], the ratio of the minimum concentration of free drug to the MIC
      [fC(min)/MIC], and the ratio of the area under the concentration-time curve for
      free drug to the MIC [fAUC/MIC]) were calculated for each patient. Classification
      and regression tree analysis was used to partition the pharmacodynamic parameters
      for prediction of the microbiological response. Monte Carlo simulation was
      utilized to determine the optimal dosing regimens needed to achieve the
      pharmacodynamic target. Fifty-six patients with pneumonia (66.1%), skin and skin
      structure infections (SSSIs) (25%), and bacteremia (8.9%) were included. Twenty
      four (42.9%) patients failed cefepime therapy. The MICs ranged from 0.75 to 96
      microg/ml, resulting in median fT > MIC, fC(m)(in)/MIC, and fAUC/MIC exposures of
      100% (range, 0.8 to 100%), 4.3 (range, 0.1 to 27.3), and 206.2 (range, 4.2 to
      1,028.7), respectively. Microbiological failure was associated with an fT > MIC
      of < or =60% (77.8% failed cefepime therapy when fT > MIC was < or =60%, whereas
      36.2% failed cefepime therapy when fT > MIC was >60%; P = 0.013). A similar fT >
      MIC target of < or =63.9% (P = 0.009) was identified when skin and skin structure
      infections were excluded. While controlling for the SSSI source (odds ratio [OR],
      0.18 [95% confidence interval, 0.03 to 1.19]; P = 0.07) and combination therapy
      (OR, 2.15 [95% confidence interval, 0.59 to 7.88]; P = 0.25), patients with fT >
      MIC values of < or =60% were 8.1 times (95% confidence interval, 1.2 to 55.6
      times) more likely to experience a poor microbiological response. Cefepime doses
      of at least 2 g every 8 h are required to achieve this target against CLSI
      defined susceptible P. aeruginosa organisms in patients with normal renal
      function. In patients with non-urinary tract infections caused by P. aeruginosa,
      achievement of cefepime exposures of >60% fT > MIC will minimize the possibility
      of a poor microbiological response.

PMID- 20038615
TI  - Rates and mechanisms of resistance development in Mycobacterium tuberculosis to a
      novel diarylquinoline ATP synthase inhibitor.
AB  - R207910 (also known as TMC207) is an investigational drug currently in clinical
      studies for the treatment of multidrug-resistant (MDR) tuberculosis. It has a
      high degree of antimycobacterial activity and is equally effective against drug
      susceptible and MDR Mycobacterium tuberculosis isolates. In the present study, we
      characterized the development of resistance to R207910 in vitro. Ninety-seven
      independent R207910-resistant mutants were selected from seven different clinical
      isolates of M. tuberculosis (three drug-susceptible and four MDR isolates) at
      10x, 30x, and 100x the MIC. At a concentration of 0.3 mg/liter (10x the MIC), the
      mutation rates ranged from 4.7 x 10(-7) to 8.9 x 10(-9) mutations per cell per
      division, and at 1.0 mg/liter (30x the MIC) the mutation rate ranged from 3.9 x
      10(-8) to 2.4 x 10(-9). No resistant mutants were obtained at 3 mg/liter (100x
      the MIC). The level of resistance ranged from 0.12 to 3.84 mg/liter for the
      mutants identified; these concentrations represent 4- to 128-fold increases in
      the MICs. For 53 of the resistant mutants, the atpE gene, which encodes a
      transmembrane and oligomeric C subunit of the ATP synthase and which was
      previously shown to be involved in resistance, was sequenced. For 15/53 mutants,
      five different point mutations resulting in five different amino acid
      substitutions were identified in the atpE gene. For 38/53 mutants, no atpE
      mutations were found and sequencing of the complete F0 ATP synthase operon (atpB,
      atpE, and atpF genes) and the F1 ATP synthase operon (atpH, atpA, atpG, atpD, and
      atpC genes) from three mutants revealed no mutations, indicating other,
      alternative resistance mechanisms. Competition assays showed no measurable
      reduction in the fitness of the mutants compared to that of the isogenic wild
      types.

PMID- 20038616
TI  - Inhibition of Porphyromonas gingivalis biofilm by oxantel.
AB  - Porphyromonas gingivalis is a major pathogen of chronic periodontitis and exists
      in a biofilm on the surface of the tooth root. Oxantel, a cholinergic
      anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm
      formation by P. gingivalis and disrupted established biofilms at concentrations
      below its MIC against planktonic cells. Oxantel was more effective against P.
      gingivalis in biofilm than metronidazole, a commonly used antibiotic for
      periodontitis.

PMID- 20038618
TI  - Detection of KPC in Acinetobacter spp. in Puerto Rico.
AB  - During an island-wide PCR-based surveillance study of beta-lactam resistance in
      multidrug-resistant (MDR) Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginosa, and Acinetobacter calcoaceticus-baumannii complex isolates obtained
      from 17 different hospitals, 10 KPC-positive Acinetobacter isolates were
      identified. DNA sequencing of the bla(KPC) gene identified KPC-2, -3, and -4 and
      a novel variant, KPC-10. This is the first report of a KPC-type beta-lactamase
      identified in Acinetobacter species.

PMID- 20038617
TI  - Lack of pharmacokinetic interaction between amdoxovir and reduced- and standard
      dose zidovudine in HIV-1-infected individuals.
AB  - Amdoxovir (AMDX) inhibits HIV-1 containing the M184V/I mutation and is rapidly
      absorbed and deaminated to its active metabolite, beta-D-dioxolane guanosine
      (DXG). DXG is synergistic with zidovudine (ZDV) in HIV-1-infected primary human
      lymphocytes. A recent in silico pharmacokinetic (PK)/enzyme kinetic study
      suggested that ZDV at 200 mg twice a day (b.i.d.) may reduce toxicity without
      compromising efficacy relative to the standard 300-mg b.i.d. dose. Therefore, an
      intense PK clinical study was conducted using AMDX/placebo, with or without ZDV,
      in 24 subjects randomized to receive oral AMDX at 500 mg b.i.d., AMDX at 500 mg
      plus ZDV at 200 or 300 mg b.i.d., or ZDV at 200 or 300 mg b.i.d. for 10 days.
      Full plasma PK profiles were collected on days 1 and 10, and complete urine
      sampling was performed on day 9. Plasma and urine concentrations of AMDX, DXG,
      ZDV, and ZDV-5'-O-glucuronide (GZDV) were measured using a validated liquid
      chromatography-tandem mass spectrometry method. Data were analyzed using
      noncompartmental methods, and multiple comparisons were performed on the log
      transformed parameters, at steady state. Coadministration of AMDX with ZDV did
      not significantly change either of the plasma PK parameters or percent recovery
      in the urine of AMDX, DXG, or ZDV/GZDV. Larger studies with AMDX/ZDV, with a
      longer duration, are warranted.

PMID- 20038619
TI  - Early curative applications of the aminoglycoside WR279396 on an experimental
      Leishmania major-loaded cutaneous site do not impair the acquisition of immunity.
AB  - Topical therapy is an attractive approach for the treatment of Leishmania major
      cutaneous leishmaniasis (CL). WR279396, an expanded-spectrum aminoglycoside
      ointment, is now in phase 3 trials. Because the application of a cream is easier
      than the injection of pentavalent antimony, many patients with CL will likely be
      treated with WR279396 soon after the onset of a lesion. However, this new
      therapeutic approach may impair the acquisition of immunity. We evaluated the
      impact of early topical therapy on acquired immunity in an optimized mouse model
      of L. major-induced CL. The efficacy of the WR279396 ointment in this model has
      been established previously. Acquired immunity was defined as the absence of
      lesions upon reinoculation of the same parasite isolate at a different skin site.
      Bioluminescence-based follow-up of luciferase-expressing L. major loads was also
      performed. In this model, the control of L. major loads at the initial
      inoculation site and the acquisition of immunity are simultaneous (day 22
      postinoculation). The clinical and parasitological efficacies of WR279396 applied
      as early as day 11 postinoculation, i.e., during the L. major multiplication
      phase, did not impair the acquisition of immunity to a second L. major challenge.
      This is reassuring from the perspective of the wide deployment of WR279396-based
      therapy in foci where L. major is endemic.

PMID- 20038620
TI  - Comparative pharmacodynamics of amphotericin B lipid complex and liposomal
      amphotericin B in a murine model of pulmonary mucormycosis.
AB  - We compared the kinetics of amphotericin B (AMB) lung accumulation and fungal
      clearance by liposomal amphotericin B (L-AMB) and amphotericin B lipid complex
      (ABLC) in a neutropenic murine model of invasive pulmonary mucormycosis (IPM).
      Immunosuppressed BALB/c mice were inoculated with 1 x 10(6) Rhizopus oryzae
      spores and administered L-AMB or ABLC at daily intravenous doses of 1, 5, or 10
      mg/kg of body weight for 5 days starting 12 h after infection. At a dose of 10
      mg/kg/day, both L-AMB and ABLC were effective at reducing the R. oryzae lung
      fungal burden and achieved lung tissue concentrations exceeding the isolate mean
      fungicidal concentration (MFC) of 8 microg/ml by 72 h. When ABLC was dosed at 5
      mg/kg/day, the ABLC-treated animals had significantly higher AMB lung
      concentrations than the L-AMB treated animals at 24 h (6.64 and 1.44 microg/g,
      respectively; P = 0.013) and 72 h (7.49 and 1.03 microg/g, respectively; P =
      0.005), and these higher concentrations were associated with improved fungal
      clearance, as determined by quantitative real-time PCR (mean conidial equivalent
      of R. oryzae DNA per lung, 4.44 +/- 0.44 and 6.57 +/- 0.74 log(10), respectively;
      P < 0.001). Analysis of the AMB tissue concentration-response relationships
      revealed that the suppression of R. oryzae growth in the lung required tissue
      concentrations that approached the MFC for the infecting isolate (50% effective
      concentration, 8.19 microg/g [95% confidence interval, 2.81 to 18.1 microg/g]).
      The rates of survival were similar in the animals treated with L-AMB and ABLC at
      10 mg/kg/day. These data suggest that higher initial doses may be required during
      L-AMB treatment than during ABLC treatment of experimental IPM.

PMID- 20038621
TI  - Stage-dependent inhibition of HIV-1 replication by antiretroviral drugs in cell
      culture.
AB  - Recent clinical trials have shown that the use of the HIV-1 integrase (IN)
      inhibitor raltegravir (RAL) results in drops in the viral load that are more
      rapid than those achieved by use of the reverse transcriptase (RT) inhibitor
      efavirenz. Previously, mathematical modeling of viral load decay that takes into
      account the stage of viral replication targeted by a drug has yielded data that
      closely approximate the clinical trial results. This model predicts greater
      inhibition of viral replication by drugs that act later in the viral replication
      cycle. In the present study, we have added drugs that target entry, reverse
      transcription, integration, or proteolytic processing to acutely infected cells
      and have shown modest viral inhibition by entry inhibitors, intermediate levels
      of inhibition by RT and IN inhibitors, and high levels of inhibition by protease
      inhibitors relative to the levels of growth for the no-drug controls. When dual
      or triple combinations of these drugs were added to acutely infected cells, we
      found that the levels of inhibition achieved by any given combination were
      comparable to those achieved by the latest-acting drug in the combination. In
      single-round infections in which the kinetics of reverse transcription and
      integration had been determined by quantitative PCR, addition of IN inhibitors at
      various times postinfection resulted in levels of inhibition equal to or greater
      than those achieved by addition of RT inhibitors. Collectively, our data provide
      in vitro evidence of the stage-dependent inhibition of HIV-1 by clinically
      relevant drugs. We discuss how stage-dependent inhibition helps to explain the
      unique viral load decay dynamics observed clinically with RAL.

PMID- 20038622
TI  - Pharmacokinetics of acyclovir and its metabolites in cerebrospinal fluid and
      systemic circulation after administration of high-dose valacyclovir in subjects
      with normal and impaired renal function.
AB  - Valacyclovir, the L-valyl ester prodrug of acyclovir (ACV), is widely prescribed
      to treat infections caused by varicella-zoster virus or herpes simplex virus.
      Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By
      mechanisms not fully understood, this occurs more frequently in the setting of
      renal impairment. We characterized the steady-state pharmacokinetics of ACV and
      its metabolites 9-[(carboxymethoxy)methyl]guanine (CMMG) and 8-hydroxy-acyclovir
      (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We
      administered multiple doses of high-dose valacyclovir to 6 subjects with normal
      renal function and 3 subjects with chronic renal impairment (creatinine clearance
      [CrCl], approximately 15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500
      mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF
      sampling throughout the dosing interval. The average steady-state concentrations
      of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation
      and the CSF among subjects with impaired renal function than among subjects with
      normal renal function. However, the CSF penetration of each analyte, reflected by
      the CSF-to-plasma area under the concentration-time curve over the 6- or 12-h
      dosing interval (AUC(tau)) ratio, did not differ based on renal function. Renal
      impairment does not alter the propensity for ACV or its metabolites to distribute
      to the CSF, but the higher concentrations in the systemic circulation, as a
      result of reduced elimination, are associated with proportionally higher
      concentrations in CSF.

PMID- 20038623
TI  - Impact of different factors on the probability of clinical response in
      tigecycline-treated patients with intra-abdominal infections.
AB  - Patients with intra-abdominal infections differ with regard to the type of
      infection and the severity of illness. However, the impact of these factors,
      together with differences in drug exposure, on clinical response is not well
      understood. Using phase 2 and 3 data for patients with complicated intra
      abdominal infections, the relative importance of tigecycline exposure, host
      factors, and disease factors, alone or in combination, for the probability of
      clinical response was examined. Patients with complicated intra-abdominal
      infections who received tigecycline intravenously as a 100-mg loading dose
      followed by 50 mg every 12 h for 5 to 14 days and who had adequate clinical,
      pharmacokinetic, and response data were evaluated. Multivariable logistic
      regression was used to identify factors associated with clinical response. A
      final multivariable logistic regression model demonstrated six factors based on
      123 patients to be predictive of clinical success: a weight of <94 kg (P =
      0.026), the absence of Pseudomonas aeruginosa in baseline cultures (P = 0.021),
      an APACHE II score of <13 (P = 0.029), non-Hispanic race (P = 0.005), complicated
      appendicitis or cholecystitis (P = 0.004), and a ratio of the area under the
      concentration-time curve (AUC) to the MIC (AUC/MIC ratio) of > or =3.1 (P =
      0.003). The average model-predicted probability of clinical success when one
      unfavorable factor was present was 0.940. This probability was lower (0.855) when
      the AUC/MIC ratio was < 3.1 and the remaining five factors were set to the
      favorable condition. The average model-predicted probability of clinical success
      in the presence of two unfavorable factors was 0.594. These findings demonstrated
      the impact of individual and multiple factors on clinical response in the context
      of drug exposure.

PMID- 20038624
TI  - Antimicrobial susceptibilities of multidrug-resistant Campylobacter jejuni and C.
      coli strains: in vitro activities of 20 antimicrobial agents.
AB  - There is a paucity of information regarding antimicrobial agents that are
      suitable to treat severe infections caused by multidrug-resistant Campylobacter
      spp. Our aim was to identify agents that are potentially effective against
      multiresistant Campylobacter strains. The in vitro activities of 20 antimicrobial
      agents against 238 Campylobacter strains were analyzed by determining MICs by the
      agar plate dilution method or the Etest. These strains were selected from 1,808
      Campylobacter isolates collected from Finnish patients between 2003 and 2005 and
      screened for macrolide susceptibility by using the disk diffusion test. The 238
      strains consisted of 183 strains with erythromycin inhibition zone diameters of <
      or =23 mm and 55 strains with inhibition zone diameters of >23 mm. Of the 238
      Campylobacter strains, 19 were resistant to erythromycin by MIC determinations
      (MIC > or = 16 microg/ml). Given that the resistant strains were identified among
      the collection of 1,808 isolates, the frequency of erythromycin resistance was
      1.1%. All erythromycin-resistant strains were multidrug resistant, with 18
      (94.7%) of them being resistant to ciprofloxacin (MIC > or = 4 microg/ml). The
      percentages of resistance to tetracycline and amoxicillin-clavulanic acid (co
      amoxiclav) were 73.7% and 31.6%, respectively. All macrolide-resistant strains
      were susceptible to imipenem, meropenem, and tigecycline. Ten (52.6%)
      multiresistant strains were identified as being Campylobacter jejuni strains, and
      9 (47.4%) were identified as being C. coli strains. These data demonstrate that
      the incidence of macrolide resistance was low but that the macrolide-resistant
      Campylobacter strains were uniformly multidrug resistant. In addition to the
      carbapenems, tigecycline was also highly effective against these multidrug
      resistant Campylobacter strains in vitro. Its efficacy for the treatment of human
      campylobacteriosis should be evaluated in clinical trials.

PMID- 20038625
TI  - Pharmacokinetics of antituberculosis drugs in pulmonary tuberculosis patients
      with type 2 diabetes.
AB  - Altered pharmacokinetics of antituberculosis drugs may contribute to an increased
      risk of tuberculosis treatment failure for diabetic patients. We previously found
      that rifampin exposure was 2-fold lower in diabetic than in nondiabetic
      tuberculosis patients during the continuation phase of treatment. We now examined
      the influence of diabetes on the pharmacokinetics of antituberculosis drugs in
      the intensive phase of tuberculosis treatment, and we evaluated the effect of
      glycemic control. For this purpose, 18 diabetic and 18 gender- and body weight
      matched nondiabetic tuberculosis patients were included in an Indonesian setting.
      Intensive pharmacokinetic sampling was performed for rifampin, pyrazinamide, and
      ethambutol at steady state. The bioavailability of rifampin was determined by
      comparing rifampin exposure after oral versus intravenous administration.
      Pharmacokinetic assessments were repeated for 10 diabetic tuberculosis patients
      after glycemic control. No differences in the areas under the concentration-time
      curves of the drugs in plasma from 0 to 24 h postdose (AUC(0-24)), the maximum
      concentrations of the drugs in plasma (C(max)), the times to C(max) (T(max)), and
      the half-lives of rifampin, pyrazinamide, and ethambutol were found between
      diabetic and nondiabetic tuberculosis patients in the intensive phase of
      tuberculosis treatment. For rifampin, oral bioavailability and metabolism were
      similar in diabetic and nondiabetic patients. The pharmacokinetic parameters of
      antituberculosis drugs were not correlated with blood glucose levels or glucose
      control. We conclude that diabetes does not alter the pharmacokinetics of
      antituberculosis drugs during the intensive phase of tuberculosis treatment. The
      reduced exposure to rifampin of diabetic patients in the continuation phase may
      be due to increased body weight and possible differences in hepatic induction.
      Further research is needed to determine the cause of increased tuberculosis
      treatment failure among diabetic patients.

PMID- 20038626
TI  - Evidence of selective sweeps in genes conferring resistance to chloroquine and
      pyrimethamine in Plasmodium falciparum isolates in India.
AB  - Treatment of Plasmodium falciparum is complicated by the emergence and spread of
      parasite resistance to many of the first-line drugs used to treat malaria.
      Antimalarial drug resistance has been associated with specific point mutations in
      several genes, suggesting that these single nucleotide polymorphisms can be
      useful in tracking the emergence of drug resistance. In India, P. falciparum
      infection can manifest itself as asymptomatic, mild, or severe malaria, with or
      without cerebral involvement. We tested whether chloroquine- and antifolate drug
      resistant genotypes would be more commonly associated with cases of cerebral
      malaria than with cases of mild malaria in the province of Jabalpur, India, by
      genotyping the dhps, dhfr, pfmdr-1, and pfcrt genes using pyrosequencing, direct
      sequencing, and real-time PCR. Further, we used microsatellites surrounding the
      genes to determine the origins and spread of the drug-resistant genotypes in this
      area. Resistance to chloroquine was essentially fixed, with 95% of the isolates
      harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1
      were found in 94%, 17%, and 77% of the isolates, respectively. Drug-resistant
      genotypes were equally likely to be associated with cerebral malaria as with mild
      malaria. We found evidence of a selective sweep in pfcrt and, to a lesser degree,
      in dhfr, indicating high levels of resistance to chloroquine and evolving
      resistance to pyrimethamine. Microsatellites surrounding pfcrt indicate that the
      resistant genotypes (SVMNT) were most similar to those found in Papua New Guinea.

PMID- 20038627
TI  - In vitro activity of CEM-101, a new fluoroketolide antibiotic, against Chlamydia
      trachomatis and Chlamydia (Chlamydophila) pneumoniae.
AB  - The in vitro activities of CEM-101, telithromycin, azithromycin, clarithromycin,
      and doxycycline against 10 isolates each of Chlamydia trachomatis and Chlamydia
      (Chlamydophila) pneumoniae were tested. The MIC at which 90% of the isolates of
      both C. trachomatis and C. pneumoniae were inhibited and the minimal bactericidal
      concentration at which 90% of the isolates were killed by CEM-101 were 0.25
      microg/ml (ranges, 0.125 to 0.5 microg/ml for C. trachomatis and 0.25 to 1.0
      microg/ml for C. pneumoniae).

PMID- 20038628
TI  - Single nucleotide polymorphism analysis of the major tripartite multidrug efflux
      pump of Escherichia coli: functional conservation in disparate animal reservoirs
      despite exposure to antimicrobial chemotherapy.
AB  - AcrAB-TolC imparts a strong intrinsic resistance phenotype to many clinically
      significant molecules in Escherichia coli. This complex is composed of a pump,
      AcrB, and a periplasmic protein, AcrA, that exports substrates through a common
      outer membrane porin, TolC. A sequence survey of the pump-specific components,
      acrA and acrB, was conducted on three discrete animal reservoirs: rodents,
      bovines, and catfish. Although two of the reservoirs (bovine and catfish) were
      agrarian, and antibiotic use (ceftiofur and oxytetracycline/Romet 30,
      respectively) was reported for them, the vast majority of structural
      polymorphisms were silent except for T104A (AcrA) and Q733R (AcrB), found in
      certain bovine-derived strains. Overall, the genes were well conserved, with high
      ratios of synonymous to nonsynonymous substitutions (d(S)/d(N) ratios),
      consistent with or, in the case of acrB, better than those of standard multilocus
      sequence typing (MLST) loci. Furthermore, predicted recombination points from
      single nucleotide polymorphism (SNP) patterns in acrB support a modular evolution
      of transporter proteins, consistent with an ancient origin. However, functional
      studies with clones representing the major silent SNPs and the nonsilent mutation
      in acrB failed to generate significant differences in resistance to a range of
      common efflux pump substrates. Interestingly, a comparison between log-phase acrA
      and acrB expression profiles yielded inconsistent trends, with acrB expression
      increasing modestly (<1.8-fold) in many strains from the antibiotic-enriched
      pools. Our results suggest that structural polymorphisms in this major efflux
      pump system may not contribute significantly to adaptive resistance by altering
      function or substrate specificity but may have a potential use in improving
      phylogenetic relationships and/or source tracking.

PMID- 20038629
TI  - Computational prediction of Caenorhabditis box H/ACA snoRNAs using genomic
      properties of their host genes.
AB  - Identification of small nucleolar RNAs (snoRNAs) in genomic sequences has been
      challenging due to the relative paucity of sequence features. Many current
      prediction algorithms rely on detection of snoRNA motifs complementary to target
      sites in snRNAs and rRNAs. However, recent discovery of snoRNAs without apparent
      targets requires development of alternative prediction methods. We present an
      approach that combines rule-based filters and a Bayesian Classifier to identify a
      class of snoRNAs (H/ACA) without requiring target sequence information. It takes
      advantage of unique attributes of their genomic organization and improved species
      specific motif characterization to predict snoRNAs that may otherwise be
      difficult to discover. Searches in the genomes of Caenorhabditis elegans and the
      closely related Caenorhabditis briggsae suggest that our method performs well
      compared to recent benchmark algorithms. Our results illustrate the benefits of
      training gene discovery engines on features restricted to particular phylogenetic
      groups and the utility of incorporating diverse data types in gene prediction.

PMID- 20038630
TI  - High-throughput quantification of splicing isoforms.
AB  - Most human messenger RNAs (mRNAs) are alternatively spliced and many exhibit
      disease-specific splicing patterns. However, the contribution of most splicing
      events to the development and maintenance of human diseases remains unclear. As
      the contribution of alternative splicing events to diagnosis and prognosis is
      becoming increasingly recognized, it becomes important to develop precise methods
      to quantify the abundance of these isoforms in clinical samples. Here we present
      a pipeline for real-time PCR annotation of splicing events (RASE) that allows
      accurate identification of a large number of splicing isoforms in human tissues.
      The RASE automatically designed specific primer pairs for 81% of all alternative
      splicing events in the NCBI build 36 database. Experimentally, the majority of
      the RASE designed primers resulted in isoform-specific amplification suitable for
      quantification in human cell lines or in formalin-fixed, paraffin-embedded (FFPE)
      RNA extract. Using this pipeline it is now possible to rapidly identify splicing
      isoform signatures in different types of human tissues or to validate complete
      sets of data generated by microarray expression profiling and deep sequencing
      techniques.

PMID- 20038632
TI  - The adenosine wedge: a new structural motif in ribosomal RNA.
AB  - Here, we present a new recurrent RNA arrangement, the so-called adenosine wedge
      (A-wedge), which is found in three places of the ribosomal RNA in both ribosomal
      subunits. The arrangement has a hierarchical structure, consisting of elements
      previously described as recurrent motifs, namely, the along-groove packing motif,
      the A-minor and the hook-turn. Within the A-wedge, these elements are involved in
      different types of cause-effect relationships, providing together for the
      particular tertiary structure of the motif.

PMID- 20038631
TI  - Accommodation of tmRNA-SmpB into stalled ribosomes: a cryo-EM study.
AB  - In eubacteria, translation of defective messenger RNAs (mRNAs) produces truncated
      polypeptides that stall on the ribosome. A quality control mechanism referred to
      as trans-translation is performed by transfer-messenger RNA (tmRNA), a
      specialized RNA acting as both a tRNA and an mRNA, associated with small protein
      B (SmpB). So far, a clear view of the structural movements of both the protein
      and RNA necessary to perform accommodation is still lacking. By using a construct
      containing the tRNA-like domain as well as the extended helix H2 of tmRNA, we
      present a cryo-electron microscopy study of the process of accommodation. The
      structure suggests how tmRNA and SmpB move into the ribosome decoding site after
      the release of EF-Tu.GDP. While two SmpB molecules are bound per ribosome in a
      preaccommodated state, our results show that during accommodation the SmpB
      protein interacting with the small subunit decoding site stays in place while the
      one interacting with the large subunit moves away. Relative to canonical
      translation, an additional movement is observed due to the rotation of H2. This
      suggests that the larger movement required to resume translation on a tmRNA
      internal open reading frame starts during accommodation.

PMID- 20038633
TI  - The Rim101p/PacC pathway and alkaline pH regulate pattern formation in yeast
      colonies.
AB  - Multicellular organisms utilize cell-to-cell signals to build patterns of cell
      types within embryos, but the ability of fungi to form organized communities has
      been largely unexplored. Here we report that colonies of the yeast Saccharomyces
      cerevisiae formed sharply divided layers of sporulating and nonsporulating cells.
      Sporulation initiated in the colony's interior, and this region expanded upward
      as the colony matured. Two key activators of sporulation, IME1 and IME2, were
      initially transcribed in overlapping regions of the colony, and this overlap
      corresponded to the initial sporulation region. The development of colony
      sporulation patterns depended on cell-to-cell signals, as demonstrated by
      chimeric colonies, which contain a mixture of two strains. One such signal is
      alkaline pH, mediated through the Rim101p/PacC pathway. Meiotic-arrest mutants
      that increased alkali production stimulated expression of an early meiotic gene
      in neighboring cells, whereas a mutant that decreased alkali production
      (cit1Delta) decreased this expression. Addition of alkali to colonies accelerated
      the expansion of the interior region of sporulation, whereas inactivation of the
      Rim101p pathway inhibited this expansion. Thus, the Rim101 pathway mediates
      colony patterning by responding to cell-to-cell pH signals. Cell-to-cell signals
      coupled with nutrient gradients may allow efficient spore formation and spore
      dispersal in natural environments.

PMID- 20038634
TI  - Alternative splicing modulates Ubx protein function in Drosophila melanogaster.
AB  - The Drosophila Hox gene Ultrabithorax (Ubx) produces a family of protein isoforms
      through alternative splicing. Isoforms differ from one another by the presence of
      optional segments-encoded by individual exons-that modify the distance between
      the homeodomain and a cofactor-interaction module termed the "YPWM" motif. To
      investigate the functional implications of Ubx alternative splicing, here we
      analyze the in vivo effects of the individual Ubx isoforms on the activation of a
      natural Ubx molecular target, the decapentaplegic (dpp) gene, within the
      embryonic mesoderm. These experiments show that the Ubx isoforms differ in their
      abilities to activate dpp in mesodermal tissues during embryogenesis.
      Furthermore, using a Ubx mutant that reduces the full Ubx protein repertoire to
      just one single isoform, we obtain specific anomalies affecting the patterning of
      anterior abdominal muscles, demonstrating that Ubx isoforms are not functionally
      interchangeable during embryonic mesoderm development. Finally, a series of
      experiments in vitro reveals that Ubx isoforms also vary in their capacity to
      bind DNA in presence of the cofactor Extradenticle (Exd). Altogether, our results
      indicate that the structural changes produced by alternative splicing have
      functional implications for Ubx protein function in vivo and in vitro. Since
      other Hox genes also produce splicing isoforms affecting similar protein domains,
      we suggest that alternative splicing may represent an underestimated regulatory
      system modulating Hox gene specificity during fly development.

PMID- 20038635
TI  - Ssz1 restores endoplasmic reticulum-associated protein degradation in cells
      expressing defective cdc48-ufd1-npl4 complex by upregulating cdc48.
AB  - The endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway
      eliminates aberrant proteins from the ER. The key role of Cdc48p-Ufd1p-Npl4p is
      indicated by impaired ERAD in Saccharomyces cerevisiae with mutations in any of
      this complex's genes. We identified SSZ1 in genetic screens for cdc48-10
      suppressors and show that it upregulates Cdc48p via the pleiotropic drug
      resistance (PDR) network. A pSSZ1 plasmid restored impaired ERAD-M of 6myc-Hmg2
      in cdc48-10, ufd1-2, and npl4-1, while SSZ1 deletion had no effect. Ssz1p
      activates Pdr1p, the PDR master regulator. Indeed, plasmids of PDR1 or its target
      gene RPN4 increased cdc48-10p levels and restored ERAD-M in cdc48-10. Rpn4p
      regulates transcription of proteasome subunits and CDC48, thus RPN4 deletion
      abolished ERAD. However, the diminished proteasome level in Deltarpn4 was
      sufficient for degrading a cytosolic substrate, whereas the impaired ERAD-M was
      the result of diminished Cdc48p and was restored by expression of pCDC48. The
      corrected ERAD-M in the hypomorphic strains of the Cdc48 partners ufd1-2 and npl4
      1 by the pCDC48 plasmid, and in cdc48-10 cells by the pcdc48-10 plasmid, combined
      with the finding that neither pSSZ1 nor pcdc48-10 restored ERAD-L of CPY*-HA,
      support our conclusion that Ssz1p suppressing effects is brought about by
      upregulating Cdc48p.

PMID- 20038636
TI  - Loss of CD34 leads to exacerbated autoimmune arthritis through increased vascular
      permeability.
AB  - CD34 is a cell surface sialomucin expressed by hematopoietic precursors,
      eosinophils, mast cells, and vascular endothelia and is suggested to play an
      integral role in mucosal inflammatory responses. Although Cd34(-/-) mice have
      normal hematopoietic cell subsets in peripheral tissues at steady state, they
      exhibit a cell recruitment defect when challenged, offering a unique opportunity
      to distinguish between local inflammatory cell proliferation and peripheral
      recruitment in disease. Autoimmune arthritis is an inflammatory disease dependent
      on hematopoietic infiltration, and in this study, we have examined the role of
      CD34 in disease development and progression. Using an autoimmune serum transfer
      model, arthritis was induced in C57BL/6 wild-type and Cd34(-/-) mice.
      Surprisingly, we found that Cd34(-/-) mice were more susceptible to arthritis
      than wild-type mice. We examined mast cell-transplanted, eosinophil-deficient,
      and bone marrow-chimeric mice to determine the role of CD34 expression on disease
      progression. These experiments excluded CD34-deficient mast cells, eosinophils,
      or hematopoietic cells as the cause of the exacerbated disease. Further study
      demonstrated that Cd34(-/-) mice exhibit increased vascular leakage at onset of
      disease and in response to TNF, which correlated with a subsequent increase in
      disease severity. We conclude that loss of CD34 expression leads to increased
      vascular permeability in the joints at onset of disease, leading to exacerbated
      arthritic disease in Cd34(-/-) mice.

PMID- 20038637
TI  - Development of promyelocytic zinc finger and ThPOK-expressing innate gamma delta
      T cells is controlled by strength of TCR signaling and Id3.
AB  - The broad-complex tramtrack and bric a brac-zinc finger transcriptional regulator
      (BTB-ZF), promyelocytic leukemia zinc finger (PLZF), was recently shown to
      control the development of the characteristic innate T cell phenotype and
      effector functions of NK T cells. Interestingly, the ectopic expression of PLZF
      was shown to push conventional T cells into an activated state that seems to be
      proinflammatory. The factors that control the normal expression of PLZF in
      lymphocytes are unknown. In this study, we show that PLZF expression is not
      restricted to NK T cells but is also expressed by a subset of gammadelta T cells,
      functionally defining distinct subsets of this innate T cell population. A second
      BTB-ZF gene, ThPOK, is important for the phenotype of the PLZF-expressing
      gammadelta T cells. Most importantly, TCR signal strength and expression of
      inhibitor of differentiation gene 3 control the frequency of PLZF-expressing
      gammadelta T cells. This study defines the factors that control the propensity of
      the immune system to produce potentially disease-causing T cell subsets.

PMID- 20038638
TI  - Progenitor cell origin plays a role in fate choices of mature B cells.
AB  - B cells, the Ab-producing cells of the immune system, develop from hematopoietic
      stem cells (HSCs) through well-defined stages during which Ig genes are
      rearranged to generate a clonal BCR. Signaling through the BCR plays a role in
      the subsequent cell fate decisions leading to the generation of three distinct
      types of B cells: B1, marginal zone, and follicular B cells. Common lymphoid
      progenitors (CLPs) are descended from HSCs, and although recent observations
      suggest that CLPs may not be physiological T cell precursors, it is generally
      accepted that CLPs are obligate progenitors for B cells. In addition, a CLP-like
      progenitor of unknown significance that lacks expression of c-kit (kit(-)CLP) was
      recently identified in the mouse model. In this study, we show that CLPs, kit(
      )CLPs and a population within the lin(-)Sca1(+)kit(+)flt3(-) HSC compartment
      generate mature B cell types in different proportions: CLPs and kit(-)CLPs show a
      stronger marginal zone/follicular ratio than lin(-)Sca1(+)kit(+)flt3(-) cells,
      whereas kit(-)CLPs show a stronger B1 bias than any other progenitor population.
      Furthermore, expression of Sca1 on B cells depends on their progenitor origin as
      B cells derived from CLPs and kit(-)CLPs express more Sca1 than those derived
      from lin(-)Sca1(+)kit(+)flt3(-) cells. These observations indicate a role for
      progenitor origin in B cell fate choices and suggest the existence of CLP
      independent B cell development.

PMID- 20038639
TI  - Phylogenetic and functional analysis identifies Ets-1 as a novel regulator of the
      Th2 cytokine gene locus.
AB  - The Th2 cytokine gene locus has emerged as a remarkable example of coordinated
      gene expression, the regulation of which seems to be rooted in an extensive array
      of cis-regulatory regions. Using a hypothesis-generating computational approach
      that integrated multispecies (n = 11) sequence comparisons with algorithm-based
      transcription factor binding-site predictions, we sought to identify
      evolutionarily conserved noncoding regions (ECRs) and motifs shared among them,
      which may underlie coregulation. Twenty-two transcription factor families were
      predicted to have binding sites in at least two Th2 ECRs. The ranking of these
      shared motifs according to their distribution and relative frequency pointed to a
      regulatory hierarchy among the transcription factor families. GATA sites were the
      most prevalent and widely distributed, consistent with the known role of GATA3 as
      a Th2 master switch. Unexpectedly, sites for ETS-domain proteins were also
      predicted within several Th2 ECRs and the majority of these sites were found to
      support Ets-1 binding in vitro and in vivo. Of note, the expression of all three
      Th2 cytokines (IL-5, -13, and -4) was significantly and selectively decreased in
      Th2 cells generated from Ets-1-deficient mice. Collectively, these data suggest
      that Ets-1 contributes to Th2 cytokine gene regulation by interacting with
      multiple cis-regulatory regions throughout the Th2 locus.

PMID- 20038641
TI  - Cutting edge: HLA-DM-mediated peptide exchange functions normally on MHC class II
      peptide complexes that have been weakened by elimination of a conserved hydrogen
      bond.
AB  - The mechanism by which HLA-DM (DM) promotes exchange of peptides bound to HLA-DR
      (DR) is still unclear. We have shown that peptide interaction with DR1 can be
      considered a folding process as evidenced by cooperativity. However, in DM
      mediated ligand exchange, prebound peptide release is noncooperative, which could
      be a function of the breaking of a critical interaction. The hydrogen bond (H
      bond) between beta-chain His(81) and the peptide backbone at the -1 position is a
      candidate for such a target. In this study, we analyze the exchange of peptides
      bound to a DR1 mutant in which formation of this H-bond is impaired. We observe
      that DM still functions normally. However, as expected of a cooperative model,
      this H-bond contributes to the overall energetics of the complex and its
      disruption impacts the ability of the exchange ligand to fold with the binding
      groove into a stable complex.

PMID- 20038640
TI  - Defective ribosomal products are the major source of antigenic peptides
      endogenously generated from influenza A virus neuraminidase.
AB  - The defective ribosomal product (DRiP) hypothesis of endogenous Ag processing
      posits that rapidly degraded forms of nascent proteins are a major source of
      peptide ligands for MHC class I molecules. Although there is broad experimental
      support for the DRiP hypothesis, careful kinetic analysis of the generation of
      defined peptide class I complexes has been limited to studies of recombinant
      vaccinia viruses expressing genes derived from other organisms. In this study, we
      show that insertion of the SIINFEKL peptide into the stalk of influenza A virus
      neuraminidase (NA) does not detectably modify NA folding, degradation, transport,
      or sp. act. when expressed in its natural context of influenza A virus infection.
      Using the 25-D1.16 mAb specific for K(b)-SIINFEKL to precisely quantitate cell
      surface complexes by flow cytometry, we demonstrate that SIINFEKL is generated in
      complete lockstep with initiation and abrogation of NA biosynthesis in both L
      K(b) fibroblast cells and DC2.4 dendritic/monocyte cells. SIINFEKL presentation
      requires active proteasomes and TAP, consistent with its generation from a
      cytosolic DRiP pool. From the difference in the shutoff kinetics of K(b)-SIINFEKL
      complex expression following protein synthesis versus proteasome inhibition, we
      estimate that the t(1/2) of the biosynthetic source of NA peptide is
      approximately 5 min. These observations extend the relevance of the DRiP
      hypothesis to viral proteins generated in their natural context.

PMID- 20038642
TI  - TLR4-mediated podosome loss discriminates gram-negative from gram-positive
      bacteria in their capacity to induce dendritic cell migration and maturation.
AB  - Chronic infections are caused by microorganisms that display effective immune
      evasion mechanisms. Dendritic cell (DC)-dependent T cell-mediated adaptive
      immunity is one of the mechanisms that have evolved to prevent the occurrence of
      chronic bacterial infections. In turn, bacterial pathogens have developed
      strategies to evade immune recognition. In this study, we show that gram-negative
      and gram-positive bacteria differ in their ability to activate DCs and that gram
      negative bacteria are far more effective inducers of DC maturation. Moreover, we
      observed that only gram-negative bacteria can induce loss of adhesive podosome
      structures in DCs, a response necessary for the induction of effective DC
      migration. We demonstrate that the ability of gram-negative bacteria to trigger
      podosome turnover and induce DC migration reflects their capacity to selectively
      activate TLR4. Examining mice defective in TLR4 signaling, we show that this DC
      maturation and migration are mainly Toll/IL-1 receptor domain-containing adaptor
      inducing IFNbeta-dependent. Furthermore, we show that these processes depend on
      the production of PGs by these DCs, suggesting a direct link between TLR4
      mediated signaling and arachidonic metabolism. These findings demonstrate that
      gram-positive and gram-negative bacteria profoundly differ in their capacity to
      activate DCs. We propose that this inability of gram-positive bacteria to induce
      DC maturation and migration is part of the armamentarium necessary for avoiding
      the induction of an effective cellular immune response and may explain the
      frequent involvement of these pathogens in chronic infections.

PMID- 20038643
TI  - Roles of Sema4D-plexin-B1 interactions in the central nervous system for
      pathogenesis of experimental autoimmune encephalomyelitis.
AB  - Although semaphorins were originally identified as axonal guidance molecules
      during neuronal development, it is emerging that several semaphorins play crucial
      roles in various phases of immune responses. Sema4D/CD100, a class IV semaphorin,
      has been shown to be involved in the nervous and immune systems through its
      receptors plexin-B1 and CD72, respectively. However, the involvement of Sema4D in
      neuroinflammation still remains unclear. We found that Sema4D promoted inducible
      NO synthase expression by primary mouse microglia, the effects of which were
      abolished in plexin-B1-deficient but not in CD72-deficient microglia. In
      addition, during the development of experimental autoimmune encephalomyelitis
      (EAE), which was induced by immunization with myelin oligodendrocyte glycoprotein
      derived peptides, we observed that the expression of Sema4D and plexin-B1 was
      induced in infiltrating mononuclear cells and microglia, respectively. Consistent
      with these expression profiles, when myelin oligodendrocyte glycoprotein-specific
      T cells derived from wild-type mice were adoptively transferred into plexin-B1
      deficient mice or bone marrow chimera mice with plexin-B1-deficient CNS resident
      cells, the development of EAE was considerably attenuated. Furthermore, blocking
      Abs against Sema4D significantly inhibited neuroinflammation during EAE
      development. Collectively, our findings demonstrate the role of Sema4D-plexin-B1
      interactions in the activation of microglia and provide their pathologic
      significance in neuroinflammation.

PMID- 20038644
TI  - T cells are required for the production of blister-inducing autoantibodies in
      experimental epidermolysis bullosa acquisita.
AB  - Epidermolysis bullosa acquisita is a prototypical organ-specific autoimmune
      disease caused by autoantibodies against type VII collagen of the dermal
      epidermal junction. Although mechanisms of autoantibody-induced blister formation
      were extensively characterized, the initiation of autoantibody production in
      autoimmune blistering diseases is still poorly defined. In the current study, we
      addressed the role of T cells for the production of blister-inducing
      autoantibodies in mice immunized with type VII collagen. To detect autoreactive
      type VII collagen-specific T cells, lymph node cells from immunized SJL mice were
      stimulated in vitro with recombinant Ag, and their proliferation was measured by
      radioactive thymidine incorporation and flow cytometry analysis of CFSE-labeled
      cells. Interestingly, using synthetic peptides of the immunogen, partly different
      T and B cell epitopes in mice immunized with type VII collagen were demonstrated.
      In contrast to wild-type mice, immunization with type VII collagen of SJL athymic
      nude mice lacking T cells did not induce an autoimmune response and blistering
      phenotype. Importantly, SJL nude mice repleted with T cells from immunized wild
      type mice showed a robust and durable autoantibody production resulting in
      subepidermal blistering disease in the recipients. Our present results
      demonstrate that T cells are required for the initiation of autoimmunity against
      type VII collagen in experimental epidermolysis bullosa acquisita and provide a
      basis for developing T cell-directed immunomodulatory strategies for this and
      related autoimmune diseases.

PMID- 20038646
TI  - Health promotion practice and the next 5 years: thoughts from the newly appointed
      editor-in-chief.

PMID- 20038645
TI  - Cutting edge: basophils are transiently recruited into the draining lymph nodes
      during helminth infection via IL-3, but infection-induced Th2 immunity can
      develop without basophil lymph node recruitment or IL-3.
AB  - Basophils are recognized as immune modulators through their ability to produce IL
      4, a key cytokine required for Th2 immunity. It has also recently been reported
      that basophils are transiently recruited into the draining lymph node (LN) after
      allergen immunization and that the recruited basophils promote the
      differentiation of naive CD4 T cells into Th2 effector cells. Using IL-3(-/-) and
      IL-3Rbeta(-/-) mice, we report in this study that the IL-3/IL-3R system is
      absolutely required to recruit circulating basophils into the draining LN
      following helminth infection. Unexpectedly, the absence of IL-3 or of basophil LN
      recruitment played little role in helminth-induced Th2 immune responses.
      Moreover, basophil depletion in infected mice did not diminish the development of
      IL-4-producing CD4 T cells. Our results reveal a previously unknown role of IL-3
      in recruiting basophils to the LN and demonstrate that basophils are not
      necessarily associated with the development of Th2 immunity during parasite
      infection.

PMID- 20038647
TI  - Be it resolved: writing resolutions to influence health policy.

PMID- 20038648
TI  - Charting your career path through clear professional values and purpose.
AB  - Clearly articulating one's professional purpose and professional values can
      clarify career direction as well as provide inspiration and ongoing career
      motivation for emerging, established, and senior health education professionals.
      Through examples and exercises, this article provides a method for clarifying and
      using professional values and purpose statements for health education
      professionals.

PMID- 20038649
TI  - Ethics and community-based participatory research: perspectives from the field.
AB  - Exploring the importance of ethical issues in the conduct of community-based
      participatory research (CBPR) continues to be an important topic for researchers
      and practitioners. This article uses the Beyond Sabor Project, a CBPR project
      implemented in the Lower Rio Grande Valley, as a case example to discuss ethical
      issues such as the importance of increasing community involvement in research,
      ensuring that communities benefit from the research, sharing leadership roles,
      and sensitive issues regarding data collection and sharing. Thereafter, this
      article concludes with a brief discussion of six principles that can inform the
      practice of ethical conduct when implementing CBPR studies. This article also
      lists additional reading resources on the importance of ethics in the conduct of
      CBPR.

PMID- 20038650
TI  - Meeting the challenge of change.
AB  - Although the largest improvements in the health of the public are likely to come
      from changing the social and behavioral conditions that influence morbidity,
      mortality, and functioning, public health training continues to focus more on how
      to bring about individual behavioral change than how to change larger social
      conditions and factors. A search of the on-line course catalogs of the 10 leading
      public health schools reveals that only 1 offers the "trifecta" of courses
      devoted to policy advocacy, media advocacy, and community organizing,
      respectively. To meet the challenge of creating large-scale change, public health
      schools need to do a better job of equipping our students with theoretical and
      practical tools in these three areas.

PMID- 20038651
TI  - Circadian window of opportunity: what have we learned from insects?

PMID- 20038652
TI  - Mottle camouflage patterns in cuttlefish: quantitative characterization and
      visual background stimuli that evoke them.
AB  - Cuttlefish and other cephalopods achieve dynamic background matching with two
      general classes of body patterns: uniform (or uniformly stippled) patterns and
      mottle patterns. Both pattern types have been described chiefly by the size scale
      and contrast of their skin components. Mottle body patterns in cephalopods have
      been characterized previously as small-to-moderate-scale light and dark skin
      patches (i.e. mottles) distributed somewhat evenly across the body surface. Here
      we move beyond this commonly accepted qualitative description by quantitatively
      measuring the scale and contrast of mottled skin components and relating these
      statistics to specific visual background stimuli (psychophysics approach) that
      evoke this type of background-matching pattern. Cuttlefish were tested on
      artificial and natural substrates to experimentally determine some primary visual
      background cues that evoke mottle patterns. Randomly distributed small-scale
      light and dark objects (or with some repetition of small-scale shapes/sizes) on a
      lighter substrate with moderate contrast are essential visual cues to elicit
      mottle camouflage patterns in cuttlefish. Lowering the mean luminance of the
      substrate without changing its spatial properties can modulate the mottle pattern
      toward disruptive patterns, which are of larger scale, different shape and higher
      contrast. Backgrounds throughout nature consist of a continuous range of spatial
      scales; backgrounds with medium-sized light/dark patches of moderate contrast are
      those in which cuttlefish Mottle patterns appear to be the most frequently
      observed.

PMID- 20038653
TI  - Dietary lipid levels have a remarkable impact on the expression of growth-related
      genes in Senegalese sole (Solea senegalensis Kaup).
AB  - In Senegalese sole (Solea senegalensis Kaup), growth is negatively correlated to
      dietary lipid levels. To understand the molecular basis of this effect a
      molecular toolbox of 12 genes, including fgf6, fst, mstn1, myf5, mrf4, myod1,
      myod2, myog, myHC, mylc2, igf1r and insr, was developed. The expression profiles
      of these genes were investigated in white muscle and liver of fish fed with three
      dietary lipid levels (4%, 12% and 20%). The expression of igf-I and igf-II was
      also examined. MRFs and myosins were only expressed in the muscle and, except for
      myf5, the general trend was a decrease in expression with an increase in dietary
      lipids. Fgf6 was identified for the first time in liver and its expression
      augmented in hepatic tissues with increasing dietary lipid levels. A similar
      tendency was observed for mstn1 and igf-I. The opposite was observed for igf1r
      expression in muscle and liver. Myog, mrf4, mylc2 and igf1r were highly
      correlated with growth and nutrient utilisation indices. In addition to its
      practical implications, this work provides a valuable contribution towards our
      understanding of the genetic networks controlling growth in teleosts.

PMID- 20038654
TI  - Proteomic and physiological responses of leopard sharks (Triakis semifasciata) to
      salinity change.
AB  - Partially euryhaline elasmobranchs may tolerate physiologically challenging,
      variable salinity conditions in estuaries as a trade-off to reduce predation risk
      or to gain access to abundant food resources. To further understand these trade
      offs and to evaluate the underlying mechanisms, we examined the responses of
      juvenile leopard sharks to salinity changes using a suite of measurements at
      multiple organizational levels: gill and rectal gland proteomes (using 2-D gel
      electrophoresis and tandem mass spectrometry), tissue biochemistry (Na(+)/K(+)
      ATPase, caspase 3/7 and chymotrypsin-like proteasome activities), organismal
      physiology (hematology, plasma composition, muscle moisture) and individual
      behavior. Our proteomics results reveal coordinated molecular responses to low
      salinity - several of which are common to both rectal gland and gill - including
      changes in amino acid and inositol (i.e. osmolyte) metabolism, energy metabolism
      and proteins related to transcription, translation and protein degradation.
      Overall, leopard sharks employ a strategy of maintaining plasma urea, ion
      concentrations and Na(+)/K(+)-ATPase activities in the short-term, possibly
      because they rarely spend extended periods in low salinity conditions in the
      wild, but the sharks osmoconform to the surrounding conditions by 3 weeks. We
      found no evidence of apoptosis at the time points tested, while both tissues
      exhibited proteomic changes related to the cytoskeleton, suggesting that leopard
      sharks remodel existing osmoregulatory epithelial cells and activate
      physiological acclimatory responses to solve the problems posed by low salinity
      exposure. The behavioral measurements reveal increased activity in the lowest
      salinity in the short-term, while activity decreased in the lowest salinity in
      the long-term. Our data suggest that physiological/behavioral trade-offs are
      involved in using estuarine habitats, and pathway modeling implicates tumor
      necrosis factor alpha (TNFalpha) as a key node of the elasmobranch hyposmotic
      response network.

PMID- 20038655
TI  - Electric signals and species recognition in the wave-type gymnotiform fish
      Apteronotus leptorhynchus.
AB  - Gymnotiformes are South American weakly electric fish that produce weak electric
      organ discharges (EOD) for orientation, foraging and communication purposes. It
      has been shown that EOD properties vary widely across species and could thus be
      used as species recognition signals. We measured and quantified the electric
      signals of various species using a landmark-based approach. Using discriminant
      function analysis to verify whether these signals are species specific based on
      different signal parameters, we found that the EOD waveform is a more specific
      cue than EOD frequency, which shows large overlap across species. Using
      Apteronotus leptorhynchus as a focal species, we then performed a series of
      playback experiments using stimuli of different species (varying in frequency,
      waveform, or both). In an experiment with restrained fish, we found, in contrast
      to what we predicted, that the choice of stimulus waveform did not affect the
      production of communication signals. In an experiment with free-swimming fish,
      the animals spent more time near the playback electrodes and produced more
      communication signals when the stimuli were within their conspecific frequency
      range. Waveform again had no measurable effect. The production of communication
      signals correlated with the frequency difference between the stimulus and the
      fish's own EOD, but approach behavior did not.

PMID- 20038656
TI  - Eating chemically defended prey: alkaloid metabolism in an invasive ladybird
      predator of other ladybirds (Coleoptera: Coccinellidae).
AB  - By comparison with studies of herbivore physiological adaptation to plant
      allelochemicals, work on predator physiological adaptation to potentially toxic
      prey has been very limited. Such studies are important in understanding how
      evolution could shape predator diets. An interesting question is the specificity
      of predator adaptation to prey allelochemicals, given that many predators consume
      diverse prey with different chemical defences. The ladybird Harmonia axyridis, an
      invasive species in America, Europe and Africa, is considered a significant
      predatory threat to native invertebrates, particularly other aphid-eating
      ladybirds of which it is a strong intraguild predator. Although ladybirds possess
      species-specific alkaloid defences, H. axyridis exhibits high tolerance for
      allospecific ladybird prey alkaloids. Nonetheless, it performs poorly on species
      with novel alkaloids not commonly occurring within its natural range. We examined
      alkaloid fate in H. axyridis larvae after consumption of two other ladybird
      species, one containing an alkaloid historically occurring within the predator's
      native range (isopropyleine) and one containing a novel alkaloid that does not
      (adaline). Our results indicate that H. axyridis rapidly chemically modifies the
      alkaloid to which it has been historically exposed to render it less harmful:
      this probably occurs outside of the gut. The novel, more toxic alkaloid persists
      in the body unchanged for longer. Our results suggest metabolic alkaloid
      specialisation, in spite of the diversity of chemically defended prey that the
      predator consumes. Physiological adaptations appear to have made H. axyridis a
      successful predator of other ladybirds; however, limitations are imposed by its
      physiology when it eats prey with novel alkaloids.

PMID- 20038658
TI  - Spatial vision in the purple sea urchin Strongylocentrotus purpuratus
      (Echinoidea).
AB  - Recent evidence that echinoids of the genus Echinometra have moderate visual
      acuity that appears to be mediated by their spines screening off-axis light
      suggests that the urchin Strongylocentrotus purpuratus, with its higher spine
      density, may have even more acute spatial vision. We analyzed the movements of 39
      specimens of S. purpuratus after they were placed in the center of a featureless
      tank containing a round, black target that had an angular diameter of 6.5 deg. or
      10 deg. (solid angles of 0.01 sr and 0.024 sr, respectively). An average
      orientation vector for each urchin was determined by testing the animal four
      times, with the target placed successively at bearings of 0 deg., 90 deg., 180
      deg. and 270 deg. (relative to magnetic east). The urchins showed no significant
      unimodal or axial orientation relative to any non-target feature of the
      environment or relative to the changing position of the 6.5 deg. target. However,
      the urchins were strongly axially oriented relative to the changing position of
      the 10 deg. target (mean axis from -1 to 179 deg.; 95% confidence interval +/- 12
      deg.; P<0.001, Moore's non-parametric Hotelling's test), with 10 of the 20
      urchins tested against that target choosing an average bearing within 10 deg. of
      either the target center or its opposite direction (two would be expected by
      chance). In addition, the average length of the 20 target-normalized bearings for
      the 10 deg. target (each the vector sum of the bearings for the four trials) were
      far higher than would be expected by chance (P<10(-10); Monte Carlo simulation),
      showing that each urchin, whether it moved towards or away from the target, did
      so with high consistency. These results strongly suggest that S. purpuratus
      detected the 10 deg. target, responding either by approaching it or fleeing it.
      Given that the urchins did not appear to respond to the 6.5 deg. target, it is
      likely that the 10 deg. target was close to the minimum detectable size for this
      species. Interestingly, measurements of the spine density of the regions of the
      test that faced horizontally predicted a similar visual resolution (8.3+/-0.5
      deg. for the interambulacrum and 11+/-0.54 deg. for the ambulacrum). The function
      of this relatively low, but functional, acuity - on par with that of the
      chambered Nautilus and the horseshoe crab - is unclear but, given the bimodal
      response, is likely to be related to both shelter seeking and predator avoidance.

PMID- 20038657
TI  - Thermal plasticity in young snakes: how will climate change affect the
      thermoregulatory tactics of ectotherms?
AB  - Climate change will result in some areas becoming warmer and others cooler, and
      will amplify the magnitude of year-to-year thermal variation in many areas. How
      will such changes affect animals that rely on ambient thermal heterogeneity to
      behaviourally regulate their body temperatures? To explore this question, we
      raised 43 captive-born tiger snakes Notechis scutatus in enclosures that provided
      cold (19-22 degrees C), intermediate (19-26 degrees C) or hot (19-37 degrees C)
      thermal gradients. The snakes adjusted their diel timing of thermoregulatory
      behaviour so effectively that when tested 14 months later, body temperatures
      (mean and maximum), locomotor speeds and anti-predator behaviours did not differ
      among treatment groups. Thus, the young snakes modified their behaviour to
      compensate for restricted thermal opportunities. Then, we suddenly shifted
      ambient conditions to mimic year-to-year variation. In contrast to the earlier
      plasticity, snakes failed to adjust to this change, e.g. snakes raised at cooler
      treatments but then shifted to hot conditions showed a higher mean body
      temperature for at least two months after the onset of the new thermal regime.
      Hence, thermal conditions experienced early in life influenced subsequent
      thermoregulatory tactics; the mean selected temperature of a snake depended more
      upon its prior raising conditions than upon its current thermoregulatory
      opportunities. Behavioural plasticity thus allows snakes to adjust to suboptimal
      thermal conditions but this plasticity is limited. The major thermoregulatory
      challenge from global climate change may not be the shift in mean values (to
      which our young snakes adjusted) but the increased year-to-year variation (with
      which our snakes proved less able to deal).

PMID- 20038659
TI  - Responses of alkaline phosphatase activity to phosphorus stress in Daphnia magna.
AB  - We examined how alkaline phosphatase (AP) activity within the bodies and in the
      materials released by the crustacean Daphnia magna responds to variable algal
      food phosphorus (P)-content. We found that Daphnia eating P-poor food (C:P
      approximately 700) had significantly higher AP activity in their bodies on a mass
      specific basis compared with individuals eating P-rich food (C:P approximately
      100). This dietary P effect on AP activity was not altered by Daphnia starvation
      but was partially related to differences in the P concentration of animal body
      homogenates. By contrast, poor P-nutrition of Daphnia lowered AP activity in
      released materials compared with that measured from their P-sufficient
      conspecifics. Moreover, AP activity in Daphnia release was lowest in animals
      consuming P-poor food for longer time periods. Our results support the hypothesis
      that AP activity increases inside P-limited Daphnia as a mechanism to increase P
      acquisition and retention from ingested algae in these nutritionally stressed
      animals. The lower level of AP activity present in the water of P-deprived
      animals could reflect a change from largely free to membrane-bound AP isotypes in
      the digestive tracts of P-starved animals or a decrease in the shedding of
      membrane-anchored AP from their intestinal lining. These results supplement
      accumulating evidence that P-poor algal food reduces the dietary mineral P
      available to Daphnia. In addition, animal body AP activity measurements, with
      some refinement, may prove useful as an in situ indicator of P-stress in aquatic
      consumers.

PMID- 20038660
TI  - The moment before touchdown: landing manoeuvres of the honeybee Apis mellifera.
AB  - Although landing is a crucial part of insect flight, it has attracted relatively
      little study. Here, we investigate, for the first time, the final moments of a
      honeybee's (Apis mellifera) landing manoeuvre. Using high-speed video recordings,
      we analyse the behaviour of bees as they approach and land on surfaces of various
      orientations. The bees enter a stable hover phase, immediately prior to
      touchdown. We have quantified behaviour during this hover phase and examined
      whether it changes as the tilt of the landing surface is varied from horizontal
      (floor), through sloped (uphill) and vertical (wall), to inverted (ceiling). The
      bees hover at a remarkably constant distance from the surface, irrespective of
      its tilt. Body inclination increases progressively as the tilt of the surface is
      increased, and is accompanied by an elevation of the antennae. The tight
      correlation between the tilt of the surface, and the orientation of the body and
      the antennae, indicates that the bee's visual system is capable of inferring the
      tilt of the surface, and pointing the antennae toward it. Touchdown is initiated
      by extending the appendage closest to the surface, namely, the hind legs when
      landing on horizontal or sloping surfaces, and the front legs or antennae when
      landing on vertical surfaces. Touchdown on inverted surfaces is most likely
      triggered by a mechanosensory signal from the antennae. Evidently, bees use a
      landing strategy that is flexibly tailored to the varying topography of the
      terrain.

PMID- 20038661
TI  - Age-dependent allocation of carotenoids to coloration versus antioxidant
      defences.
AB  - Aging is commonly attributed to age-related changes in oxidative damage due to an
      increased production of reactive oxygen species (ROS) and a weakened efficacy of
      enzymatic antioxidants. These age-related changes might therefore modify the use
      of dietary antioxidants, including carotenoids. As carotenoids are closely
      associated with the expression of secondary sexual signals, the allocation of
      carotenoids to sexual signal versus antioxidant defences may vary with age. In
      this study, we explored how carotenoid-based ornament and antioxidant activity
      varied with age and how an inflammatory-induced oxidative burst affected ornament
      and antioxidant activity across a range of ages. Using zebra finches (Taeniopygia
      guttata) as a model species, we assessed circulating carotenoids, beak coloration
      and the plasma antioxidant status of birds of different ages before and after an
      inflammatory challenge. Our results show that old individuals display similar
      carotenoid-based sexual signals regardless of the availability of circulating
      carotenoids, suggesting a terminal investment of old individuals in their last
      reproductive event. Additionally, we found that an inflammatory insult induced a
      decrease in the total antioxidant activity and in the expression of a carotenoid
      based sexual signal in the oldest individuals. These results suggest that old
      individuals pay an extra cost of immune activation possibly because the
      efficiency of antioxidant machinery varies with age.

PMID- 20038662
TI  - Limits to sustained energy intake XII: is the poor relation between resting
      metabolic rate and reproductive performance because resting metabolism is not a
      repeatable trait?
AB  - Many studies have investigated the consequences of individual variation in
      resting metabolic rate at thermoneutrality (RMRt) on reproductive performance.
      Despite strong theoretical reasons for expecting such an association, results
      have generally been disappointing. A fundamental assumption of these studies is
      that RMRt is a repeatable trait. We examined repeatability of RMRt in female MF1
      mice over short (15 days apart; N=238) and long intervals (110 days apart; N=33).
      In the long-term experiment, after the first RMRt measurement, females were
      separated in two groups: the first was kept virgin (N=16); the second was allowed
      to breed (N=17) and measured 15 days after they had weaned their pups. We also
      examined the association between RMRt and reproduction. We used Pearson's
      correlation (r) and intraclass correlation coefficients (rho) to estimate
      repeatability. There was a strong effect of body mass on RMRt for all
      measurements. Over the short interval, repeatability was significant for body
      mass (r=0.86; rho=0.86), RMRt (r=0.68; rho=0.68,) and residual-RMRt (r=0.58;
      rho=0.58). Over long intervals, repeatability of residual-RMRt was high in virgin
      females (r=0.59; rho=0.60), but not in the breeders (r=0.38; rho=0.39); body mass
      was repeatable only for non-breeders measured by r (r=0.55). There was no
      significant correlation between RMRt or residual-RMRt and litter size or litter
      mass. In conclusion, RMRt and residual-RMRt are highly repeatable traits in
      virgin MF1 female mice. The lack of association between non-reproductive RMRt and
      reproductive performance in MF1 mice does not come about because of its poor
      repeatability.

PMID- 20038663
TI  - Correlation between aquaporin and water permeability in response to vasotocin,
      hydrin and {beta}-adrenergic effectors in the ventral pelvic skin of the tree
      frog Hyla japonica.
AB  - The ventral pelvic skin of the tree frog Hyla japonica expresses two kinds of
      arginine vasotocin (AVT)-stimulated aquaporins (AQP-h2 and AQP-h3), which affect
      the capacity of the frog's skin to absorb water. As such, it can be used as a
      model system for analyzing the molecular mechanisms of water permeability. We
      investigated AQP dynamics and water permeability in the pelvic skin of H.
      japonica following challenge with AVT, hydrins (intermediate peptides of pro-AVT)
      and beta-adrenergic effectors. In the in vivo experiment, both AQP-h2 and AQP-h3
      proteins were translocated to the apical plasma membrane in the principal cells
      of the first-reacting cell (FRC) layer in the pelvic skin following challenge
      with AVT, hydrin 1 and hydrin 2, thereby increasing the water permeability of the
      pelvic skin. The beta-adrenergic receptor agonist isoproterenol (IP) and its
      anatagonist propranolol (PP) in combination with AVT or hydrins were used as
      challenge in the in vitro experiment. IP increased water permeability whereas PP
      inhibited it, and both events were well correlated with the translocation of the
      AQPs to the apical membrane. In the PP+AVT-treated skins, labels for AQP-h2 and
      AQP-h3 were differentially visible among the principal cells; the apical plasma
      membrane of some cells was labeled while others were not, indicating that the
      response of PP or AVT is different from cell to cell. These results provide
      morphological evidence that the principal cells of the FRC layers may have two
      kinds of receptors: a V2 receptor and beta-adrenergic receptor.

PMID- 20038665
TI  - Predator detection enables juvenile Lymnaea to form long-term memory.
AB  - Learning and memory provide the flexibility an organism requires to respond to
      changing social and ecological conditions. Juvenile Lymnaea have previously been
      shown to have a diminished capacity to form long-term memory (LTM) following
      operant conditioning of aerial respiratory behavior. Juvenile Lymnaea, however,
      can form LTM following classical conditioning of appetitive behaviors. Here, we
      demonstrate that laboratory-reared juvenile Lymnaea have the ability to detect
      the presence of a sympatric predator (i.e. crayfish) and respond to the predator
      by altering their aerial respiratory behavior. In addition to increasing their
      total breathing time, predator detection confers on juvenile Lymnaea an enhanced
      capability to form LTM following operant conditioning of aerial respiratory
      behavior. That is, these juveniles now have the ability to form long-lasting
      memory. These data support the hypothesis that biologically relevant levels of
      stress associated with predator detection induce behavioral phenotypic
      alterations (i.e. enhanced LTM formation) in juveniles, which may increase their
      fitness. These data also support the notion that learning and memory formation in
      conjunction with predator detection is a form of inducible defense.

PMID- 20038664
TI  - Cellular mechanisms of acid secretion in the posterior midgut of the larval
      mosquito (Aedes aegypti).
AB  - The gut contents of larval mosquitoes are alkalinized by the anterior midgut and
      reacidified by the posterior midgut. In the present study the cellular mechanisms
      of reacidification were studied in isolated, perfused posterior midgut by
      measuring the transepithelial voltage (V(te)) and the rate of acid secretion as
      indicated by the color change of m-cresol purple during intervals of perfusion
      stop. The lumen-positive V(te) and reacidification were significantly increased
      by serotonin (0.2 mumol l(-1)). The V-type H(+)-ATPase inhibitor concanamycin A
      (10 mumol l(-1)) on the luminal side inhibited acidification and decreased V(te).
      On the hemolymph side the carbonic anhydrase (CA) inhibitor acetazolamide (1 mmol
      l(-1)) almost abolished V(te), but had no effect on acidification. Similarly,
      hemolymph-side DIDS (0.1 mmol l(-1)), DPC (0.5 mmol l(-1)), amiloride (1 mmol l(
      1)) and ouabain (2.5 mmol l(-1)) significantly reduced V(te), whereas Ba(2+) (5
      mmol l(-1)) was without effect. DPC and amiloride also reduced V(te) when applied
      to the luminal side of the epithelium. Unilateral substitution of gluconate for
      Cl(-) affected V(te) in a way consistent with a greater permeability for Cl(-)
      versus Na(+). Cl(-) replacement in the lumen decreased V(te), whereas replacement
      on the hemolymph side increased it. Bilateral replacement left the control
      voltage unaffected. Na(+) replacement on either side of the tissue reduced V(te)
      to different degrees. Omission of luminal amino acids was followed by a
      significant decrease in V(te). Except for concanamycin A, none of the above
      manipulations impaired acidification, indicating that acidification requires only
      the apical proton pump. However, the chemical source of secreted H(+) is still
      unknown and needs to be investigated.

PMID- 20038666
TI  - Olfactory sensitivity to bile fluid and bile salts in the European eel (Anguilla
      anguilla), goldfish (Carassius auratus) and Mozambique tilapia (Oreochromis
      mossambicus) suggests a 'broad range' sensitivity not confined to those produced
      by conspecifics alone.
AB  - Teleosts have high olfactory sensitivity to bile salts. To assess whether this
      phenomenon is involved in intra-specific chemical communication alone, or is part
      of a more ;broad range' sensitivity to bile salts produced by heterospecifics, we
      investigated possible differences in the odour of bile between the sexes and
      among different species - the eel (Anguilla anguilla), goldfish (Carassius
      auratus) and Mozambique tilapia (Oreochromis mossambicus) - using the electro
      olfactogram (EOG). We also identified the main bile constituents by liquid
      chromatography and mass spectrometry. There were marked differences in olfactory
      response of the eel to thin-layer chromatography fractions of bile from both
      sexes, and mature and immature conspecifics. Smaller differences were seen in the
      potency of fractions of bile from male and female goldfish and tilapia. Eels,
      goldfish and tilapia demonstrated similar olfactory sensitivity to bile from a
      range of different species, with no apparent correlation between the olfactory
      potency of bile and a phylogenetic closeness and/or similarity of diet of the
      donor to the receiver. The three species were able to detect odorants in thin
      layer chromatography fractions of heterospecific bile even in the absence of
      activity in conspecific bile. Eels, goldfish and tilapia responded to both
      sulphated C(27) bile salts (5beta-scymnol-sulphate and 5alpha-cyprinol sulphate)
      and to taurine-conjugated C(24) bile salts (taurochenodeoxycholic acid,
      taurolithocholic acid and taurocholic acid), irrespective of whether these bile
      salts were present in conspecific bile. Together, these results suggest that
      teleosts have a broad-range olfactory sensitivity to bile salts, with potential
      roles in both intra-specific chemical communication and in inter-specific
      interactions.

PMID- 20038667
TI  - The influence of strain and activation on the locomotor function of rat ankle
      extensor muscles.
AB  - The ankle extensor muscles of the rat have different mechanical and physiological
      properties, providing a means of studying how changes in locomotor demands
      influence muscle fascicle behaviour, force and mechanical power output in
      different populations of muscle fibre types. Muscle fascicle strain, strain rate
      and activation patterns in the soleus, plantaris and medial gastrocnemius muscles
      of the rat were quantified from sonomicrometric and myoelectric data, collected
      during treadmill locomotion under nine velocity/incline conditions. Significant
      differences in peak-to-peak muscle fascicle strains and strain rates were
      identified between the three muscles (P<0.001, all cases), with much smaller
      strains (<0.1) and strain rates (<0.5 s(-1)) occurring in soleus and plantaris
      compared with medial gastrocnemius (>0.2 and >1.0 s(-1), respectively). The
      proportion of stride duration that each muscle was active (duty cycle) differed
      between locomotor conditions as did the timing of the activation and deactivation
      phases. A simple Hill-based muscle model was used to determine the influence of
      muscle activation relative to maximum fascicle strain and duty cycle on total
      force production and mechanical power output, from a slow and a fast muscle
      fibre, simulated through two peak-to-peak strain cycles (0.1 and 0.3). The
      predictions of the model did not complement conclusions that may be drawn from
      the observation of myoelectric timing and fascicle strain trajectories in each of
      the muscles. The model predicted that changes in mechanical power output were
      more sensitive to changes in activation parameters than to changes in strain
      trajectories, with subtle changes in activation phase and duty cycle
      significantly affecting predicted mechanical power output.

PMID- 20038669
TI  - The role of granules within viscous capture threads of orb-weaving spiders.
AB  - Sticky viscous prey capture threads form the spiral elements of spider orb-webs
      and are responsible for retaining insects that strike a web. These threads are
      formed of regularly spaced aqueous droplets that surround a pair of supporting
      axial fibers. When a thread is flattened on a microscope slide a small, opaque
      granule can usually be seen within each droplet. These granules have been thought
      to be the glycoprotein glue that imparts thread adhesion. Both independent
      contrast and standard regressions showed that granule size is directly related to
      droplet volume and indicated that granule volume is about 15% of droplet volume.
      We attempted to find support for the hypothesized adhesive role of granules by
      establishing an association between the contact surface area and volume of these
      granules and the stickiness of the viscous threads of 16 species in the context
      of a six-variable model that describes thread stickiness. However, we found that
      granule size made either an insignificant or a small negative contribution to
      thread stickiness. Consequently, we hypothesize that granules serve to anchor
      larger, surrounding layers of transparent glycoprotein glue to the axial fibers
      of the thread, thereby equipping droplets to resist slippage on the axial fibers
      as these droplets generate adhesion, elongate under a load, and transfer force to
      the axial fibers.

PMID- 20038668
TI  - Behavioural state affects motion-sensitive neurones in the fly visual system.
AB  - The strength of stimulus-induced responses at the neuronal and the behavioural
      level often depends on the internal state of an animal. Within pathways
      processing sensory information and eventually controlling behavioural responses,
      such gain changes can originate at several sites. Using motion-sensitive lobula
      plate tangential cells (LPTCs) of blowflies, we address whether and in which way
      information processing changes for two different states of motor activity. We
      distinguish between the two states on the basis of haltere movements. Halteres
      are the evolutionarily transformed hindwings of flies. They oscillate when the
      animals walk or fly. LPTCs mediate, amongst other behaviours, head optomotor
      responses. These are either of large or small amplitude depending on the state of
      motor activity. Here we find that LPTC responses also depend on the motor
      activity of flies. In particular, LPTC responses are enhanced when halteres
      oscillate. Nevertheless, the response changes of LPTCs do not account for the
      corresponding large gain changes of head movements. Moreover, haltere activity
      itself does not change the activity of LPTCs. Instead, we propose that a central
      signal associated with motor activity changes the gain of head optomotor
      responses and the response properties of LPTCs.

PMID- 20038671
TI  - Research on resilience supports prior research and theory in human development
      that has clearly established the link between growth and development that
      progresses naturally in the presence of certain environmental characteristics.

PMID- 20038670
TI  - Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by
      p38-MAPK and JNKs in Mytilus galloprovincialis (Lamarck); a pro-survival
      response.
AB  - In the present study we investigated the signal transduction cascades triggered
      by acute thermal stress in Mytilus galloprovincialis gills. This particular
      species has been reported to exhibit a significant tolerance to high
      temperatures; thus, it was intriguing to examine the molecular mechanisms
      responsible for this extraordinary trait. In particular, exposure to 30 degrees C
      was found to cause a significant and sustained stimulation of p38-MAPK
      phosphorylation while the activation profile of JNKs was transient and relatively
      moderate. We also observed that hyperthermia induced apoptosis as a delayed
      response, with both MAPK subfamilies rapidly translocating to the nucleus. The
      phosphorylation of cJun, ATF2 and NFkappaB was detected next. Using selective
      inhibitors, phosphorylation of these transcription factors was established to be
      dependent on p38-MAPK or JNKs. Subsequently, potential changes in gene expression
      were assessed. In this context, hyperthermia resulted in the transcriptional
      upregulation of Hsp70 and MT20 genes with a widely known salutary effect,
      preserving mussel fitness and performance under adverse environmental conditions.
      Interestingly, p38-MAPK and JNKs were found to mediate the hyperthermia-induced
      Hsp70 and MT20 upregulation as well as the delayed induction of apoptosis under
      the interventions studied. Overall this is, to our knowledge, the first time that
      an insight into the compensatory survival ;programme' initiated in Mytilus
      galloprovincialis gills, contributing to this organism's exceptional tolerance to
      thermal stress, has been gained. In particular, we provide evidence demonstrating
      the principal role of p38-MAPK and JNKs in transducing the stress signal via
      mobilization of specific transcription factors and the transcriptional
      upregulation of cytoprotective genes.

PMID- 20038673
TI  - Exploring the evidence in pediatric hematology and oncology nursing through the
      "article of the month".
AB  - As the scope of pediatric hematology and oncology nursing expands, nurses are
      challenged with staying current in the evidence guiding their practice. Nurse
      reported barriers to accessing and utilizing research include lack of time as
      well as difficulty in accessing, understanding, and synthesizing findings.
      Journal clubs provide a process to guide nurses in the review of current
      literature related to their practice and promote utilization of research and
      evidence-based practice among nurses. This article describes the transition of an
      in-person journal club to an electronically delivered "Article of the Month." The
      "Article of the Month" is offered six times each year and is posted on the
      service line's password-protected intranet website. Oversight of the "Article of
      the Month" is provided by the service line clinical nurse specialist who selects
      articles based on an annual learning needs assessment and develops a quiz to
      assess learning and promote critical thinking among nursing staff. Outcomes
      include anecdotal reports of increased staff confidence in managing emergent
      patient care needs and greater appreciation of nursing care issues for children
      with cancer. Areas for future development include exploring options for
      increasing in-person discussion of issues addressed in the "Article of the Month"
      among staff members, extending the "Article of the Month" to nurses in other
      service areas who care for children with cancer, and increasing staff
      participation in article selection and quiz item development. An ultimate goal is
      to develop formal evaluation strategies to link this educational strategy to
      clinical outcomes.

PMID- 20038672
TI  - Respiratory symptoms and acute painful episodes in sickle cell disease.
AB  - The authors examined the prevalence of respiratory symptoms and determined
      whether respiratory symptoms were associated with prevalence of chest pain and
      number of acute painful episodes in children and adolescents with sickle cell
      disease. Participants (N = 93; 44 females, 49 males; mean age 9.8 +/- 4.3 years)
      reported coughing in the morning (21.5%), at night (31.2%), and during exercise
      (30.1%). Wheezing occurred both when they had a cold or infection (29.0%) and
      when they did not have (23.7%) a cold or infection. Sleep was disturbed by
      wheezing in 20.4%. Among the 76 patients who were school-age (>5 years), 19.7% of
      patients missed more than 4 days of school because of respiratory symptoms. The
      majority of patients reported having acute painful episodes (82.8%), and most
      (66.7%) reported having chest pain during acute painful episodes in the previous
      12 months. Participants with acute pain episodes greater than 3 during the
      previous 12 months had significantly higher reports of breathing difficulties (P
      = .01) and chest pain (P = .002). The high number of respiratory symptoms (cough
      and wheeze) among patients with sickle cell disease may trigger acute painful
      episodes. Early screening and recognition, ongoing monitoring, and proactive
      management of respiratory symptoms may minimize the number of acute painful
      episodes.

PMID- 20038675
TI  - Elaine Fuchs: A love for science that's more than skin deep. Interviewed by Ben
      Short.

PMID- 20038677
TI  - Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in
      mammalian cells.
AB  - The mammalian mitochondrial inner membrane fusion protein OPA1 is controlled by
      complex patterns of alternative splicing and proteolysis. A subset of OPA1
      isoforms is constitutively cleaved by YME1L. Other isoforms are not cleaved by
      YME1L, but they are cleaved when mitochondria lose membrane potential or
      adenosine triphosphate. In this study, we show that this inducible cleavage is
      mediated by a zinc metalloprotease called OMA1. We find that OMA1 small
      interfering RNA inhibits inducible cleavage, helps retain fusion competence, and
      slows the onset of apoptosis, showing that OMA1 controls OPA1 cleavage and
      function. We also find that OMA1 is normally cleaved from 60 to 40 kD by another
      as of yet unidentified protease. Loss of membrane potential causes 60-kD protein
      to accumulate, suggesting that OMA1 is attenuated by proteolytic degradation. We
      conclude that a proteolytic cascade controls OPA1. Inducible cleavage provides a
      mechanism for quality control because proteolytic inactivation of OPA1 promotes
      selective removal of defective mitochondrial fragments by preventing their fusion
      with the mitochondrial network.

PMID- 20038678
TI  - Regulation of OPA1 processing and mitochondrial fusion by m-AAA protease
      isoenzymes and OMA1.
AB  - Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1,
      whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria
      induces OPA1 processing and results in mitochondrial fragmentation, allowing the
      selective removal of damaged mitochondria. In this study, we demonstrate that two
      classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner
      membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA
      (ATPase associated with diverse cellular activities [m-AAA]) protease, variable
      assemblies of the conserved subunits paraplegin, AFG3L1 and -2, and the ATP
      independent peptidase OMA1. Functionally redundant isoenzymes of the m-AAA
      protease ensure the balanced accumulation of long and short isoforms of OPA1
      required for mitochondrial fusion. The loss of AFG3L2 in mouse tissues, down
      regulation of AFG3L1 and -2 in mouse embryonic fibroblasts, or the expression of
      a dominant-negative AFG3L2 variant in human cells decreases the stability of long
      OPA1 isoforms and induces OPA1 processing by OMA1. Moreover, cleavage by OMA1
      causes the accumulation of short OPA1 variants if mitochondrial DNA is depleted
      or mitochondrial activities are impaired. Our findings link distinct peptidases
      to constitutive and induced OPA1 processing and shed new light on the
      pathogenesis of neurodegenerative disorders associated with mutations in m-AAA
      protease subunits.

PMID- 20038676
TI  - Role of A-type lamins in signaling, transcription, and chromatin organization.
AB  - A-type lamins (lamins A and C), encoded by the LMNA gene, are major protein
      constituents of the mammalian nuclear lamina, a complex structure that acts as a
      scaffold for protein complexes that regulate nuclear structure and functions.
      Interest in these proteins has increased in recent years with the discovery that
      LMNA mutations cause a variety of human diseases termed laminopathies, including
      progeroid syndromes and disorders that primarily affect striated muscle, adipose,
      bone, and neuronal tissues. In this review, we discuss recent research supporting
      the concept that lamin A/C and associated nuclear envelope proteins regulate gene
      expression in health and disease through interplay with signal transduction
      pathways, transcription factors, and chromatin-associated proteins.

PMID- 20038679
TI  - Cellular IAPs inhibit a cryptic CD95-induced cell death by limiting RIP1 kinase
      recruitment.
AB  - A role for cellular inhibitors of apoptosis (IAPs [cIAPs]) in preventing CD95
      death has been suspected but not previously explained mechanistically. In this
      study, we find that the loss of cIAPs leads to a dramatic sensitization to CD95
      ligand (CD95L) killing. Surprisingly, this form of cell death can only be blocked
      by a combination of RIP1 (receptor-interacting protein 1) kinase and caspase
      inhibitors. Consistently, we detect a large increase in RIP1 levels in the CD95
      death-inducing signaling complex (DISC) and in a secondary cytoplasmic complex
      (complex II) in the presence of IAP antagonists and loss of RIP1-protected cells
      from CD95L/IAP antagonist-induced death. Cells resistant to CD95L/IAP antagonist
      treatment could be sensitized by short hairpin RNA-mediated knockdown of cellular
      FLICE-inhibitory protein (cFLIP). However, only cFLIP(L) and not cFLIP(S)
      interfered with RIP1 recruitment to the DISC and complex II and protected cells
      from death. These results demonstrate a fundamental role for RIP1 in CD95
      signaling and provide support for a physiological role of caspase-independent
      death receptor-mediated cell death.

PMID- 20038680
TI  - Opposite-polarity motors activate one another to trigger cargo transport in live
      cells.
AB  - Intracellular transport is typically bidirectional, consisting of a series of
      back and forth movements. Kinesin-1 and cytoplasmic dynein require each other for
      bidirectional transport of intracellular cargo along microtubules; i.e.,
      inhibition or depletion of kinesin-1 abolishes dynein-driven cargo transport and
      vice versa. Using Drosophila melanogaster S2 cells, we demonstrate that
      replacement of endogenous kinesin-1 or dynein with an unrelated, peroxisome
      targeted motor of the same directionality activates peroxisome transport in the
      opposite direction. However, motility-deficient versions of motors, which retain
      the ability to bind microtubules and hydrolyze adenosine triphosphate, do not
      activate peroxisome motility. Thus, any pair of opposite-polarity motors,
      provided they move along microtubules, can activate one another. These results
      demonstrate that mechanical interactions between opposite-polarity motors are
      necessary and sufficient for bidirectional organelle transport in live cells.

PMID- 20038681
TI  - The binding of NCAM to FGFR1 induces a specific cellular response mediated by
      receptor trafficking.
AB  - Neural cell adhesion molecule (NCAM) associates with fibroblast growth factor
      (FGF) receptor-1 (FGFR1). However, the biological significance of this
      interaction remains largely elusive. In this study, we show that NCAM induces a
      specific, FGFR1-mediated cellular response that is remarkably different from that
      elicited by FGF-2. In contrast to FGF-induced degradation of endocytic FGFR1,
      NCAM promotes the stabilization of the receptor, which is recycled to the cell
      surface in a Rab11- and Src-dependent manner. In turn, FGFR1 recycling is
      required for NCAM-induced sustained activation of various effectors. Furthermore,
      NCAM, but not FGF-2, promotes cell migration, and this response depends on FGFR1
      recycling and sustained Src activation. Our results implicate NCAM as a
      nonconventional ligand for FGFR1 that exerts a peculiar control on the
      intracellular trafficking of the receptor, resulting in a specific cellular
      response. Besides introducing a further level of complexity in the regulation of
      FGFR1 function, our findings highlight the link of FGFR recycling with sustained
      signaling and cell migration and the critical role of these events in dictating
      the cellular response evoked by receptor activation.

PMID- 20038683
TI  - Reliable detection of dead microbial cells by using fluorescent hydrazides.
AB  - We have developed a new method for accurate quantification of dead microbial
      cells. This technique employs the simultaneous use of fluorescent hydrazides and
      nucleic acid dyes. Fluorescent hydrazides allow detection of cells that cannot be
      detected with currently used high-affinity nucleic acid dyes. This is
      particularly important for nongrowing bacterial populations and for multicellular
      communities containing physiologically heterogeneous cell populations, such as
      colonies and biofilms.

PMID- 20038682
TI  - The Chlamydomonas reinhardtii BBSome is an IFT cargo required for export of
      specific signaling proteins from flagella.
AB  - In humans, seven evolutionarily conserved genes that cause the cilia-related
      disorder Bardet-Biedl syndrome (BBS) encode proteins that form a complex termed
      the BBSome. The function of the BBSome in the cilium is not well understood. We
      purified a BBSome-like complex from Chlamydomonas reinhardtii flagella and found
      that it contains at least BBS1, -4, -5, -7, and -8 and undergoes intraflagellar
      transport (IFT) in association with a subset of IFT particles. C. reinhardtii
      insertional mutants defective in BBS1, -4, and -7 assemble motile, full-length
      flagella but lack the ability to phototax. In the bbs4 mutant, the assembly and
      transport of IFT particles are unaffected, but the flagella abnormally accumulate
      several signaling proteins that may disrupt phototaxis. We conclude that the
      BBSome is carried by IFT but is an adapter rather than an integral component of
      the IFT machinery. C. reinhardtii BBS4 may be required for the export of
      signaling proteins from the flagellum via IFT.

PMID- 20038684
TI  - Evaluation of Lactobacillus sobrius/L. amylovorus as a new microbial marker of
      pig manure.
AB  - Based on a comparison of the dominant microbial populations in 17 pig manure
      samples and using a molecular typing method, we identified a species,
      Lactobacillus sobrius and Lactobacillus amylovorus (which now are considered a
      single species and are designated L. sobrius/amylovorus here), that was
      consistently found in manure. The aim of the present study was to confirm by real
      time PCR the relevance of this species as a marker of pig fecal contamination.
      The specificity of L. sobrius/amylovorus was evaluated in human and animal DNA
      extracted from feces. The real-time PCR assay then was applied to water samples,
      including effluents from urban wastewater treatment plants, runoff water, and
      rivers. L. sobrius/amylovorus was consistently present in all samples of swine
      origin: 48 fecal samples, 18 from raw manure and 10 from biologically treated
      manure at mean concentrations of 7.2, 5.9, and 5.0 log(10) cells/g, respectively.
      The species was not detected in any of the other livestock feces (38 samples from
      cattle and 16 from sheep), in the 27 human fecal samples, or in the 13 effluent
      samples from urban wastewater treatment plants. Finally, L. sobrius/amylovorus
      was not detected in runoff water contaminated by cattle slurry, but it was
      quantified at concentrations ranging from 3.7 to 6.5 log(10) cells/100 ml in
      runoff water collected after pig manure was spread on soil. Among the stream
      water samples in which cultured Escherichia coli was detected, 23% tested
      positive for L. sobrius/amylovorus. The results of this study indicate that the
      quantification of L. sobrius/amylovorus using real-time PCR will be useful for
      identifying pig fecal contamination in surface waters.

PMID- 20038685
TI  - Indigenous and environmental modulation of frequencies of mutation in
      Lactobacillus plantarum.
AB  - Reliability of microbial (starter) strains in terms of quality, functional
      properties, growth performance, and robustness is essential for industrial
      applications. In an industrial fermentation process, the bacterium should be able
      to successfully withstand various adverse conditions during processing, such as
      acid, osmotic, temperature, and oxidative stresses. Besides the evolved defense
      mechanisms, stress-induced mutations participate in adaptive evolution for
      survival under stress conditions. However, this may lead to accumulation of
      mutant strains, which may be accompanied by loss of desired functional
      properties. Defining the effects of specific fermentation or processing
      conditions on the mutation frequency is an important step toward preventing loss
      of genome integrity and maintaining the productivity of industrial strains.
      Therefore, a set of Lactobacillus plantarum mutator reporter strains suitable for
      qualitative and quantitative analysis of low-frequency mutation events was
      developed. The mutation reporter system constructed was validated by using
      chemical mutagenesis (N-methyl-N'-nitro-N-nitrosoguanidine) and by controlled
      expression of endogenous candidate mutator genes (e.g., a truncated derivative of
      the L. plantarum hexA gene). Growth at different temperatures, under low-pH
      conditions, at high salt concentrations, or under starvation conditions did not
      have a significant effect on the mutation frequency. However, incubation with
      sublethal levels of hydrogen peroxide resulted in a 100-fold increase in the
      mutation frequency compared to the background mutation frequency. Importantly,
      when cells of L. plantarum were adapted to 42 degrees C prior to treatment with
      sublethal levels of hydrogen peroxide, there was a 10-fold increase in survival
      after peroxide treatment, and there was a concomitant 50-fold decrease in the
      mutation frequency. These results show that specific environmental conditions
      encountered by bacteria may significantly influence the genetic stability of
      strains, while protection against mutagenic conditions may be obtained by
      pretreatment of cultures with other, nonmutagenic stress conditions.

PMID- 20038686
TI  - Involvement of a novel ABC transporter and monoalkyl phthalate ester hydrolase in
      phthalate ester catabolism by Rhodococcus jostii RHA1.
AB  - Phthalate esters (PEs) are important environmental pollutants. While the
      biodegradation of the parent compound, phthalate (PTH), is well characterized,
      the biodegradation of PEs is not well understood. In particular, prior to this
      study, genes involved in the uptake and hydrolysis of these compounds were not
      conclusively identified. We found that Rhodococcus jostii RHA1 could grow on a
      variety of monoalkyl PEs, including methyl, butyl, hexyl, and 2-ethylhexyl PTHs.
      Strain RHA1 could not grow on most dialkyl PEs, but suspensions of cells grown on
      PTH transformed dimethyl, diethyl, dipropyl, dibutyl, dihexyl and di-(2
      ethylhexyl) PTHs. The major products of these dialkyl PEs were PTH and the
      corresponding monoalkyl PEs, and minor products resulted from the shortening of
      the alkyl side chains. RHA1 exhibited an inducible, ATP-dependent uptake system
      for PTH with a K(m) of 22 microM. The deletion and complementation of the patB
      gene demonstrated that the ATP-binding cassette (ABC) transporter encoded by
      patDABC is required for the uptake of PTH and monoalkyl PEs by RHA1. The
      hydrolase encoded by patE of RHA1 was expressed in Escherichia coli. PatE
      specifically hydrolyzed monoalkyl PEs to PTH but did not transform dialkyl PEs or
      other aromatic esters. This investigation of RHA1 elucidates key processes that
      are consistent with the environmental fate of PEs.

PMID- 20038687
TI  - pilF Polymorphism-based PCR to distinguish vibrio vulnificus strains potentially
      dangerous to public health.
AB  - Vibrio vulnificus is a heterogeneous species that comprises strains virulent and
      avirulent for humans and fish, and it is grouped into three biotypes. In this
      report, we describe a PCR-based methodology that allows both the species
      identification and discrimination of those isolates that could be considered
      dangerous to public health. Discrimination is based on the amplification of a
      variable region located within the gene pilF, which seems to be associated with
      potential human pathogenicity, regardless of the biotype of the strain.

PMID- 20038688
TI  - Assessing niche separation among coexisting Limnohabitans strains through
      interactions with a competitor, viruses, and a bacterivore.
AB  - We investigated potential niche separation in two closely related (99.1% 16S rRNA
      gene sequence similarity) syntopic bacterial strains affiliated with the R-BT065
      cluster, which represents a subgroup of the genus Limnohabitans. The two strains,
      designated B4 and D5, were isolated concurrently from a freshwater reservoir.
      Differences between the strains were examined through monitoring interactions
      with a bacterial competitor, Flectobacillus sp. (FL), and virus- and predator
      induced mortality. Batch-type cocultures, designated B4+FL and D5+FL, were
      initiated with a similar biomass ratio among the strains. The proportion of each
      cell type present in the cocultures was monitored based on clear differences in
      cell sizes. Following exponential growth for 28 h, the cocultures were amended by
      the addition of two different concentrations of live or heat-inactivated viruses
      concentrated from the reservoir. Half of virus-amended treatments were inoculated
      immediately with an axenic flagellate predator, Poterioochromonas sp. The
      presence of the predator, of live viruses, and of competition between the strains
      significantly affected their population dynamics in the experimentally
      manipulated treatments. While strains B4 and FL appeared vulnerable to
      environmental viruses, strain D5 did not. Predator-induced mortality had the
      greatest impact on FL, followed by that on D5 and then B4. The virus-vulnerable
      B4 strain had smaller cells and lower biomass yield, but it was less subject to
      grazing. In contrast, the seemingly virus-resistant D5, with slightly larger
      grazing-vulnerable cells, was competitive with FL. Overall, our data suggest
      contrasting ecophysiological capabilities and partial niche separation in two
      coexisting Limnohabitans strains.

PMID- 20038690
TI  - Lyophilization prior to direct DNA extraction from bovine feces improves the
      quantification of Escherichia coli O157:H7 and Campylobacter jejuni.
AB  - Lyophilization was used to concentrate bovine feces prior to DNA extraction and
      analysis using real-time PCR. Lyophilization significantly improved the
      sensitivity of detection compared to that in fresh feces and was associated with
      reliable quantification of both Escherichia coli O157:H7 and Campylobacter jejuni
      bacteria present in feces at concentrations ranging between 2 log(10) and 6
      log(10) CFU g(-)(1).

PMID- 20038689
TI  - Selection of a Bacillus pumilus strain highly active against Ceratitis capitata
      (Wiedemann) larvae.
AB  - Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), the Mediterranean fruit
      fly (medfly), is one of the most important fruit pests worldwide. The medfly is a
      polyphagous species that causes losses in many crops, which leads to huge
      economic losses. Entomopathogenic bacteria belonging to the genus Bacillus have
      been proven to be safe, environmentally friendly, and cost-effective tools to
      control pest populations. As no control method for C. capitata based on these
      bacteria has been developed, isolation of novel strains is needed. Here, we
      report the isolation of 115 bacterial strains and the results of toxicity
      screening with adults and larvae of C. capitata. As a result of this analysis, we
      obtained a novel Bacillus pumilus strain, strain 15.1, that is highly toxic to C.
      capitata larvae. The toxicity of this strain for C. capitata was related to the
      sporulation process and was observed only when cultures were incubated at low
      temperatures before they were used in a bioassay. The mortality rate for C.
      capitata larvae ranged from 68 to 94% depending on the conditions under which the
      culture was kept before the bioassay. Toxicity was proven to be a special
      characteristic of the newly isolated strain, since other B. pumilus strains did
      not have a toxic effect on C. capitata larvae. The results of the present study
      suggest that B. pumilus 15.1 could be considered a strong candidate for
      developing strategies for biological control of C. capitata.

PMID- 20038691
TI  - Identity, diversity, and molecular phylogeny of the endophytic mycobiota in the
      roots of rare wild rice (Oryza granulate) from a nature reserve in Yunnan, China.
AB  - Rice (Oryza sativa L.) is, on a global scale, one of the most important food
      crops. Although endophytic fungi and bacteria associated with rice have been
      investigated, little is known about the endophytic fungi of wild rice (Oryza
      granulate) in China. Here we studied the root endophytic mycobiota residing in
      roots of O. granulate by the use of an integrated approach consisting of
      microscopy, cultivation, ecological indices, and direct PCR. Microscopy confirmed
      the ubiquitousness of dark septate endophytes (DSEs) and sclerotium-like
      structures in root tissues. Isolations from 204 root segments from 15 wild rice
      plants yielded 58 isolates, for which 31 internal transcribed spacer (ITS)-based
      genotypes were recorded. The best BLAST match indicated that 34.5% of all taxa
      encountered may represent hitherto undescribed species. Most of the fungi were
      isolated with a very low frequency. Calculation of ecological indices and
      estimation of taxon accumulation curves indicated a high diversity of fungal
      species. A culture-independent approach was also performed to analyze the
      endophytic fungal community. Three individual clone libraries were constructed.
      Using a threshold of 90% similarity, 35 potentially different sequences
      (phylotypes) were found among 186 positive clones. Phylogenetic analysis showed
      that frequently detected clones were classified as Basidiomycota, and 60.2% of
      total analyzed clones were affiliated with unknown taxa. Exophiala,
      Cladophialophora, Harpophora, Periconia macrospinosa, and the
      Ceratobasidium/Rhizoctonia complex may act as potential DSE groups. A comparison
      of the fungal communities characterized by the two approaches demonstrated
      distinctive fungal groups, and only a few taxa overlapped. Our findings indicate
      a complex and rich endophytic fungal consortium in wild rice roots, thus offering
      a potential bioresource for establishing a novel model of plant-fungal
      mutualistic interactions.

PMID- 20038692
TI  - Long-term persistence and leaching of Escherichia coli in temperate maritime
      soils.
AB  - Enteropathogen contamination of groundwater, including potable water sources, is
      a global concern. The spreading on land of animal slurries and manures, which can
      contain a broad range of pathogenic microorganisms, is considered a major
      contributor to this contamination. Some of the pathogenic microorganisms applied
      to soil have been observed to leach through the soil into groundwater, which
      poses a risk to public health. There is a critical need, therefore, for
      characterization of pathogen movement through the vadose zone for assessment of
      the risk to groundwater quality due to agricultural activities. A lysimeter
      experiment was performed to investigate the effect of soil type and condition on
      the fate and transport of potential bacterial pathogens, using Escherichia coli
      as a marker, in four Irish soils (n = 9). Cattle slurry (34 tonnes per ha) was
      spread on intact soil monoliths (depth, 1 m; diameter, 0.6 m) in the spring and
      summer. No effect of treatment or the initial soil moisture on the E. coli that
      leached from the soil was observed. Leaching of E. coli was observed
      predominantly from one soil type (average, 1.11 +/- 0.77 CFU ml(-1)), a poorly
      drained Luvic Stagnosol, under natural rainfall conditions, and preferential flow
      was an important transport mechanism. E. coli was found to have persisted in
      control soils for more than 9 years, indicating that autochthonous E. coli
      populations are capable of becoming naturalized in the low-temperature
      environments of temperate maritime soils and that they can move through soil.
      This may compromise the use of E. coli as an indicator of fecal pollution of
      waters in these regions.

PMID- 20038693
TI  - Distribution and diversity of Escherichia coli populations in the South Nation
      River drainage basin, eastern Ontario, Canada.
AB  - We investigated the prevalence and diversity of Escherichia coli strains isolated
      from surface waters from multiple watersheds within the South Nation River basin
      in eastern Ontario, Canada. The basin is composed of mixed but primarily
      agricultural land uses. From March 2004 to November 2007, a total of 2,004
      surface water samples were collected from 24 sampling sites. E. coli densities
      ranged from undetectable to 1.64 x 10(5) CFU 100 ml(-1) and were correlated with
      stream order and proximity to livestock production systems. The diversity of
      21,307 E. coli isolates was characterized using repetitive extragenic palindromic
      PCR (rep-PCR), allowing for the identification of as many as 7,325 distinct
      genotypes, without capturing all of the diversity. The community was temporally
      and spatially dominated by a few dominant genotypes (clusters of more than 500
      isolates) and several genotypes of intermediary abundance (clustering between 10
      and 499 isolates). Simpson diversity indices, assessed on a normalized number of
      isolates per sample, ranged from 0.050 to 0.668. Simpson indices could be
      statistically discriminated on the basis of year and stream order, but land use,
      discharge, weather, and water physical-chemical properties were not statistically
      important discriminators. The detection of Campylobacter species was associated
      with statistically lower Simpson indices (greater diversity; P < 0.05).
      Waterborne E. coli isolates from genotypes of dominant and intermediary abundance
      were clustered with isolates obtained from fecal samples collected in the study
      area over the same period, and 90% of the isolates tested proved to share
      genotypes with fecal isolates. Overall, our data indicated that the densities and
      distribution of E. coli in these mixed-use watersheds were linked to stream order
      and livestock-based land uses. Waterborne E. coli populations that were distinct
      from fecal isolates were detected and, on this basis, were possibly naturalized
      E. coli strains.

PMID- 20038694
TI  - Genome-wide screening and identification of factors affecting the biosynthesis of
      prodigiosin by Hahella chejuensis, using Escherichia coli as a surrogate host.
AB  - A marine bacterium, Hahella chejuensis, recently has attracted attention due to
      its lytic activity against a red-tide dinoflagellate. The algicidal function
      originates from its red pigment, prodigiosin, which also exhibits
      immunosuppressive or anticancer activity. Genome sequencing and functional
      analysis revealed a gene set contained in the hap gene cluster that is
      responsible for the biosynthesis of prodigiosin. To screen for the factors
      affecting the prodigiosin biosynthesis, we constructed a plasmid library of the
      H. chejuensis genomic DNA, introduced it into Escherichia coli strains harboring
      the hap cluster, and observed changes in production of the red pigment. Among the
      screened clones, hapXY genes whose products constitute a two-component signal
      transduction system were elucidated as positive regulators of the pigment
      production. In addition, an Hfq-dependent, noncoding region located at one end of
      the hap cluster was confirmed to play roles in regulation. Identification of
      factors involved in the regulation of prodigiosin biosynthesis should help in
      understanding how the prodigiosin-biosynthetic pathway is organized and
      controlled and also aid in modulating the overexpression of prodigiosin in a
      heterologous host, such as E. coli, or in the natural producer, H. chejuensis.

PMID- 20038695
TI  - NoxE NADH oxidase and the electron transport chain are responsible for the
      ability of Lactococcus lactis to decrease the redox potential of milk.
AB  - The redox potential plays a major role in the microbial and sensorial quality of
      fermented dairy products. The redox potential of milk (around 400 mV) is mainly
      due to the presence of oxygen and many other oxidizing compounds. Lactococcus
      lactis has a strong ability to decrease the redox potential of milk to a negative
      value (-220 mV), but the molecular mechanisms of milk reduction have never been
      addressed. In this study, we investigated the impact of inactivation of genes
      encoding NADH oxidases (noxE and ahpF) and components of the electron transport
      chain (ETC) (menC and noxAB) on the ability of L. lactis to decrease the redox
      potential of ultrahigh-temperature (UHT) skim milk during growth under aerobic
      and anaerobic conditions. Our results revealed that elimination of oxygen is
      required for milk reduction and that NoxE is mainly responsible for the rapid
      removal of oxygen from milk before the exponential growth phase. The ETC also
      contributes slightly to oxygen consumption, especially during the stationary
      growth phase. We also demonstrated that the ETC is responsible for the decrease
      in the milk redox potential from 300 mV to -220 mV when the oxygen concentration
      reaches zero or under anaerobic conditions. This suggests that the ETC is
      responsible for the reduction of oxidizing compounds other than oxygen. Moreover,
      we found great diversity in the reducing activities of natural L. lactis strains
      originating from the dairy environment. This diversity allows selection of
      specific strains that can be used to modulate the redox potential of fermented
      dairy products to optimize their microbial and sensorial qualities.

PMID- 20038696
TI  - Global transcriptional, physiological, and metabolite analyses of the responses
      of Desulfovibrio vulgaris hildenborough to salt adaptation.
AB  - The response of Desulfovibrio vulgaris Hildenborough to salt adaptation (long
      term NaCl exposure) was examined by performing physiological, global
      transcriptional, and metabolite analyses. Salt adaptation was reflected by
      increased expression of genes involved in amino acid biosynthesis and transport,
      electron transfer, hydrogen oxidation, and general stress responses (e.g., heat
      shock proteins, phage shock proteins, and oxidative stress response proteins).
      The expression of genes involved in carbon metabolism, cell growth, and phage
      structures was decreased. Transcriptome profiles of D. vulgaris responses to salt
      adaptation were compared with transcriptome profiles of D. vulgaris responses to
      salt shock (short-term NaCl exposure). Metabolite assays showed that glutamate
      and alanine accumulated under salt adaptation conditions, suggesting that these
      amino acids may be used as osmoprotectants in D. vulgaris. Addition of amino
      acids (glutamate, alanine, and tryptophan) or yeast extract to the growth medium
      relieved salt-related growth inhibition. A conceptual model that links the
      observed results to currently available knowledge is proposed to increase our
      understanding of the mechanisms of D. vulgaris adaptation to elevated NaCl
      levels.

PMID- 20038697
TI  - Biogenic silver for disinfection of water contaminated with viruses.
AB  - The presence of enteric viruses in drinking water is a potential health risk.
      Growing interest has arisen in nanometals for water disinfection, in particular
      the use of silver-based nanotechnology. In this study, Lactobacillus fermentum
      served as a reducing agent and bacterial carrier matrix for zerovalent silver
      nanoparticles, referred to as biogenic Ag(0). The antiviral action of biogenic
      Ag(0) was examined in water spiked with an Enterobacter aerogenes-infecting
      bacteriophage (UZ1). Addition of 5.4 mg liter(-1) biogenic Ag(0) caused a 4.0-log
      decrease of the phage after 1 h, whereas the use of chemically produced silver
      nanoparticles (nAg(0)) showed no inactivation within the same time frame. A
      control experiment with 5.4 mg liter(-1) ionic Ag+ resulted in a similar
      inactivation after 5 h only. The antiviral properties of biogenic Ag(0) were also
      demonstrated on the murine norovirus 1 (MNV-1), a model organism for human
      noroviruses. Biogenic Ag(0) was applied to an electropositive cartridge filter
      (NanoCeram) to evaluate its capacity for continuous disinfection. Addition of
      31.25 mg biogenic Ag(0) m(-2) on the filter (135 mg biogenic Ag(0) kg(-1) filter
      medium) caused a 3.8-log decline of the virus. In contrast, only a 1.5-log
      decrease could be obtained with the original filter. This is the first report to
      demonstrate the antiviral efficacy of extracellular biogenic Ag(0) and its
      promising opportunities for continuous water disinfection.

PMID- 20038698
TI  - Bibersteinia trehalosi inhibits the growth of Mannheimia haemolytica by a
      proximity-dependent mechanism.
AB  - Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently
      causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis
      canadensis) under experimental conditions. Paradoxically, Bibersteinia
      (Pasteurella) trehalosi and Pasteurella multocida have been isolated from BHS
      pneumonic lungs much more frequently than M. haemolytica. These observations
      suggest that there may be an interaction between these bacteria, and we
      hypothesized that B. trehalosi overgrows or otherwise inhibits the growth of M.
      haemolytica. Growth curves (monoculture) demonstrated that B. trehalosi has a
      shorter doubling time ( approximately 10 min versus approximately 27 min) and
      consistently achieves 3-log higher cell density (CFU/ml) compared to M.
      haemolytica. During coculture M. haemolytica growth was inhibited when B.
      trehalosi entered stationary phase (6 h) resulting in a final cell density for M.
      haemolytica that was 6 to 9 logs lower than expected with growth in the absence
      of B. trehalosi. Coculture supernatant failed to inhibit M. haemolytica growth on
      agar or in broth, indicating no obvious involvement of lytic phages,
      bacteriocins, or quorum-sensing systems. This observation was confirmed by
      limited growth inhibition of M. haemolytica when both pathogens were cultured in
      the same media but separated by a filter (0.4-microm pore size) that limited
      contact between the two bacterial populations. There was significant growth
      inhibition of M. haemolytica when the populations were separated by membranes
      with a pore size of 8 mum that allowed free contact. These observations
      demonstrate that B. trehalosi can both outgrow and inhibit M. haemolytica growth
      with the latter related to a proximity- or contact-dependent mechanism.

PMID- 20038699
TI  - Effects of carbon dioxide on growth of proteolytic Clostridium botulinum, its
      ability to produce neurotoxin, and its transcriptome.
AB  - The antimicrobial gas carbon dioxide is frequently used in modified atmosphere
      packaging. In the present study, the effects of CO2 (10 to 70%, vol/vol) on gene
      expression (measured using quantitative reverse transcription-PCR and a whole
      genome DNA microarray) and neurotoxin formation (measured using an enzyme-linked
      immunosorbent assay [ELISA]) by proteolytic Clostridium botulinum type A1 strain
      ATCC 3502 were studied during the growth cycle. Interestingly, in marked contrast
      to the situation with nonproteolytic C. botulinum types B and E, CO2 had little
      effect on any of these parameters. At all CO2 concentrations, relative expression
      of neurotoxin cluster genes peaked in the transition between exponential and
      stationary phases, with evidence of a second rise in expression in late
      stationary phase. Microarray analysis enabled identification of coding sequences
      whose expression profiles matched those of the neurotoxin cluster. Further
      research is needed to determine whether these are connected to neurotoxin
      formation or are merely growth phase associated.

PMID- 20038700
TI  - Characterization of ozone disinfection of murine norovirus.
AB  - Despite the importance of human noroviruses (NoVs) in public health, little
      information concerning the effectiveness of ozone against NoVs is available. We
      determined the efficacy of ozone disinfection using murine norovirus (MNV) as a
      surrogate of human NoV. MNV in ozone demand-free buffer was exposed to a
      predetermined dose of ozone at two different pHs and temperatures. The virus
      remaining in the solution was analyzed by plaque assay, real-time TaqMan reverse
      transcriptase PCR (RT-PCR) (short template), and long-template conventional RT
      PCR. Under all conditions, more than 99% of the MNV was inactivated by ozone at 1
      mg/liter within 2 min. Both RT-PCR assays significantly underestimated the
      inactivation of MNV, compared with that measured by plaque assay. Our results
      indicate that NoV may be more resistant to ozone than has been previously
      reported. Nevertheless, proper ozone disinfection practices can be used to easily
      control its transmission in water.

PMID- 20038701
TI  - Development of a common oligonucleotide reference standard for microarray data
      normalization and comparison across different microbial communities.
AB  - High-density functional gene arrays have become a powerful tool for environmental
      microbial detection and characterization. However, microarray data normalization
      and comparison for this type of microarray remain a challenge in environmental
      microbiology studies because some commonly used normalization methods (e.g.,
      genomic DNA) for the study of pure cultures are not applicable. In this study, we
      developed a common oligonucleotide reference standard (CORS) method to address
      this problem. A unique 50-mer reference oligonucleotide probe was selected to co
      spot with gene probes for each array feature. The complementary sequence was
      synthesized and labeled for use as the reference target, which was then spiked
      and cohybridized with each sample. The signal intensity of this reference target
      was used for microarray data normalization and comparison. The optimal amount or
      concentration were determined to be ca. 0.5 to 2.5% of a gene probe for the
      reference probe and ca. 0.25 to 1.25 fmol/microl for the reference target based
      on our evaluation with a pilot array. The CORS method was then compared to dye
      swap and genomic DNA normalization methods using the Desulfovibrio vulgaris whole
      genome microarray, and significant linear correlations were observed. This method
      was then applied to a functional gene array to analyze soil microbial
      communities, and the results demonstrated that the variation of signal
      intensities among replicates based on the CORS method was significantly lower
      than the total intensity normalization method. The developed CORS provides a
      useful approach for microarray data normalization and comparison for studies of
      complex microbial communities.

PMID- 20038702
TI  - Identification of a two-component regulatory pathway essential for Mn(II)
      oxidation in Pseudomonas putida GB-1.
AB  - Bacterial manganese(II) oxidation has a profound impact on the biogeochemical
      cycling of Mn and the availability of the trace metals adsorbed to the surfaces
      of solid Mn(III, IV) oxides. The Mn(II) oxidase enzyme was tentatively identified
      in Pseudomonas putida GB-1 via transposon mutagenesis: the mutant strain GB-1
      007, which fails to oxidize Mn(II), harbors a transposon insertion in the gene
      cumA. cumA encodes a putative multicopper oxidase (MCO), a class of enzymes
      implicated in Mn(II) oxidation in other bacterial species. However, we show here
      that an in-frame deletion of cumA did not affect Mn(II) oxidation. Through
      complementation analysis of the oxidation defect in GB-1-007 with a cosmid
      library and subsequent sequencing of candidate genes we show the causative
      mutation to be a frameshift within the mnxS1 gene that encodes a putative sensor
      histidine kinase. The frameshift mutation results in a truncated protein lacking
      the kinase domain. Multicopy expression of mnxS1 restored Mn(II) oxidation to GB
      1-007 and in-frame deletion of mnxS1 resulted in a loss of oxidation in the wild
      type strain. These results clearly demonstrated that the oxidation defect of GB-1
      007 is due to disruption of mnxS1, not cumA::Tn5, and that CumA is not the Mn(II)
      oxidase. mnxS1 is located upstream of a second sensor histidine kinase gene,
      mnxS2, and a response regulator gene, mnxR. In-frame deletions of each of these
      genes also led to the loss of Mn(II) oxidation. Therefore, we conclude that the
      MnxS1/MnxS2/MnxR two-component regulatory pathway is essential for Mn(II)
      oxidation in P. putida GB-1.

PMID- 20038703
TI  - Genes involved in long-chain alkene biosynthesis in Micrococcus luteus.
AB  - Aliphatic hydrocarbons are highly appealing targets for advanced cellulosic
      biofuels, as they are already predominant components of petroleum-based gasoline
      and diesel fuels. We have studied alkene biosynthesis in Micrococcus luteus ATCC
      4698, a close relative of Sarcina lutea (now Kocuria rhizophila), which 4 decades
      ago was reported to biosynthesize iso- and anteiso-branched, long-chain alkenes.
      The underlying biochemistry and genetics of alkene biosynthesis were not
      elucidated in those studies. We show here that heterologous expression of a three
      gene cluster from M. luteus (Mlut_13230-13250) in a fatty acid-overproducing
      Escherichia coli strain resulted in production of long-chain alkenes,
      predominantly 27:3 and 29:3 (no. carbon atoms: no. C=C bonds). Heterologous
      expression of Mlut_13230 (oleA) alone produced no long-chain alkenes but
      unsaturated aliphatic monoketones, predominantly 27:2, and in vitro studies with
      the purified Mlut_13230 protein and tetradecanoyl-coenzyme A (CoA) produced the
      same C(27) monoketone. Gas chromatography-time of flight mass spectrometry
      confirmed the elemental composition of all detected long-chain alkenes and
      monoketones (putative intermediates of alkene biosynthesis). Negative controls
      demonstrated that the M. luteus genes were responsible for production of these
      metabolites. Studies with wild-type M. luteus showed that the transcript copy
      number of Mlut_13230-13250 and the concentrations of 29:1 alkene isomers (the
      dominant alkenes produced by this strain) generally corresponded with bacterial
      population over time. We propose a metabolic pathway for alkene biosynthesis
      starting with acyl-CoA (or-ACP [acyl carrier protein]) thioesters and involving
      decarboxylative Claisen condensation as a key step, which we believe is catalyzed
      by OleA. Such activity is consistent with our data and with the homology
      (including the conserved Cys-His-Asn catalytic triad) of Mlut_13230 (OleA) to
      FabH (beta-ketoacyl-ACP synthase III), which catalyzes decarboxylative Claisen
      condensation during fatty acid biosynthesis.

PMID- 20038704
TI  - Identification of a secreted lipolytic esterase in Propionibacterium
      freudenreichii, a ripening process bacterium involved in Emmental cheese
      lipolysis.
AB  - Lipolysis plays an important role in the formation of cheese flavor. In Emmental
      cheese, the main part of lipolysis has been associated with the presence of
      Propionibacterium freudenreichii, a species used as a ripening culture. Our aim
      was to identify the most probable lipolytic esterase(s) involved in cheese
      lipolysis by P. freudenreichii. Since cheese lipolysis mainly occurs during P.
      freudenreichii growth, we hypothesized that P. freudenreichii possesses secreted
      lipolytic esterase(s). For 12 putative esterase genes previously identified from
      the genome of P. freudenreichii CIRM1, the level of expression was quantified by
      real-time reverse transcriptase (RT)-PCR, and the subcellular localization of
      esterases was predicted in silico. The esterase activity in extracellular and
      intracellular extracts of P. freudenreichii was characterized by zymography, and
      the extracellular esterases were identified by mass spectrometry. Finally, the
      best candidate was overexpressed in the same strain. All of the 12 genes encoding
      putative esterases were expressed. Esterase PF#279 was predicted to be secreted
      in the medium, PF#774 to be surface exposed, and the 10 remaining putative
      esterases to be intracellular. Zymography revealed that esterase activities in
      culture supernatant differed from the ones detected in intracellular extracts.
      PF#279 was identified as the sole esterase present in culture supernatant.
      Transformed P. freudenreichii CIRM1 clones overexpressing PF#279 showed 5 to 8
      times more lipolytic activity on milk fat than the wild-type strain. Combining in
      silico, biochemical, and genetic approaches, we showed that PF#279 is the sole
      secreted esterase in P. freudenreichii and is active on milk fat. Therefore, it
      is likely a key component in cheese lipolysis by P. freudenreichii.

PMID- 20038705
TI  - Genes involved in yellow pigmentation of Cronobacter sakazakii ES5 and influence
      of pigmentation on persistence and growth under environmental stress.
AB  - Cronobacter spp. are opportunistic food-borne pathogens that are responsible for
      rare but highly fatal cases of meningitis and necrotizing enterocolitis in
      neonates. While the operon responsible for yellow pigmentation in Cronobacter
      sakazakii strain ES5 was described recently, the involvement of additional genes
      in pigment expression and the influence of pigmentation on the fitness of
      Cronobacter spp. have not been investigated. Thus, the aim of this study was to
      identify further genes involved in pigment expression in Cronobacter sakazakii
      ES5 and to assess the influence of pigmentation on growth and persistence under
      conditions of environmental stress. A knockout library was created using random
      transposon mutagenesis. The screening of 9,500 mutants for decreased pigment
      production identified 30 colorless mutants. The mapping of transposon insertion
      sites revealed insertions in not only the carotenoid operon but also in various
      other genes involved in signal transduction, inorganic ions, and energy
      metabolism. To determine the effect of pigmentation on fitness, colorless mutants
      (DeltacrtE, DeltacrtX, and DeltacrtY) were compared to the yellow wild type using
      growth and inactivation experiments, a macrophage assay, and a phenotype array.
      Among other findings, the colorless mutants grew at significantly increased rates
      under osmotic stress compared to that of the yellow wild type while showing
      increased susceptibility to desiccation. Moreover, DeltacrtE and DeltacrtY
      exhibited increased sensitivity to UVB irradiation.

PMID- 20038707
TI  - Methanotrophic communities in Brazilian ferralsols from naturally forested,
      afforested, and agricultural sites.
AB  - Conversion of forests to farmland permanently lowers atmospheric methane
      consumption due to unresolved reasons. Alphaproteobacterial methanotrophs were
      predominant in forested soils and gammaproteobacterial species were predominant
      in farmland soils of subtropical ferralsols in Brazil. The capability of
      atmospheric methane consumption was obliterated in farmland soils, suggesting a
      shift from oligotrophic to copiotrophic species.

PMID- 20038706
TI  - Abundance of ammonia-oxidizing archaea and bacteria along an estuarine salinity
      gradient in relation to potential nitrification rates.
AB  - Abundance of ammonia-oxidizing Archaea (AOA) was found to be always greater than
      that of ammonia-oxidizing Bacteria along an estuarine salinity gradient, and AOA
      abundance was highest at intermediate salinity. However, AOA abundance did not
      correlate with potential nitrification rates. This lack of correlation may be due
      to methodological limitations or alternative energy sources.

PMID- 20038708
TI  - Establishment of cyanophycin biosynthesis in Pichia pastoris and optimization by
      use of engineered cyanophycin synthetases.
AB  - Two strains of the methylotrophic yeast Pichia pastoris were used to establish
      cyanophycin (multi-L-arginyl-poly-L-aspartic acid [CGP]) synthesis and to explore
      the applicability of this industrially widely used microorganism for the
      production of this polyamide. Therefore, the CGP synthetase gene from the
      cyanobacterium Synechocystis sp. strain PCC 6308 (cphA(6308)) was expressed under
      the control of the alcohol oxidase 1 promoter, yielding CGP contents of up to
      10.4% (wt/wt), with the main fraction consisting of the soluble form of the
      polymer. To increase the polymer contents and to obtain further insights into the
      structural or catalytic properties of the enzyme, site-directed mutagenesis was
      applied to cphA(6308) and the mutated gene products were analyzed after
      expression in P. pastoris and Escherichia coli, respectively. CphA(6308)Delta1,
      which was truncated by one amino acid at the C terminus; point mutated
      CphA(6308)C595S; and the combined double-mutant CphA(6308)Delta1C595S protein
      were purified. They exhibited up to 2.5-fold higher enzyme activities of 4.95
      U/mg, 3.20 U/mg, and 4.17 U/mg, respectively, than wild-type CphA(6308) (2.01
      U/mg). On the other hand, CphA proteins truncated by two (CphA(6308)Delta2) or
      three (CphA(6308)Delta3) amino acids at the C terminus showed similar or reduced
      CphA enzyme activity in comparison to CphA(6308). In flask experiments, a maximum
      of 14.3% (wt/wt) CGP was detected after the expression of CphA(6308)Delta1 in P.
      pastoris. For stabilization of the expression plasmid, the his4 gene from
      Saccharomyces cerevisiae was cloned into the expression vector used and the
      constructs were transferred to histidine auxotrophic P. pastoris strain GS115.
      Parallel fermentations at a one-to-one scale revealed 26 degrees C and 6.0 as the
      optimal temperature and pH, respectively, for CGP synthesis. After optimization
      of fermentation parameters, medium composition, and the length of the cultivation
      period, CGP contents could be increased from 3.2 to 13.0% (wt/wt) in cells of P.
      pastoris GS115 expressing CphA(6308) and up to even 23.3% (wt/wt) in cells of P.
      pastoris GS115 expressing CphA(6308)Delta1.

PMID- 20038709
TI  - beta-(1,3)-Glucan exposure assessment by passive airborne dust sampling and new
      sensitive immunoassays.
AB  - Associations between house dust-associated beta-(1,3)-glucan exposure and airway
      inflammatory reactions have been reported, while such exposures in early
      childhood have been suggested to protect against asthma and wheezing. Most
      epidemiological studies have used reservoir dust samples and an inhibition enzyme
      immunoassay (EIA) for beta-(1,3)-glucan exposure assessment. The objective of
      this study was to develop inexpensive but highly sensitive enzyme immunoassays to
      measure airborne beta-(1,3)-glucans in low-exposure environments, like homes.
      Specificities of available anti-beta-(1,3)-glucan antibodies were defined by
      direct and inhibition experiments. Three suitable antibody combinations were
      selected for sandwich EIAs. beta-(1,3)-Glucans in passive airborne dust collected
      with an electrostatic dust fall collector (EDC) and floor dust from seven homes
      were measured with the three EIAs. Floor dust samples were additionally analyzed
      in the inhibition EIA. The sandwich EIAs were sensitive enough for airborne
      glucan measurement and showed different specificities for commercial glucans,
      while the beta-(1,3)-glucan levels in house dust samples correlated strongly. The
      feasibility of measuring glucans in airborne dust with the recently introduced
      EDC method was further investigated by selecting the most suitable of the three
      EIAs to measure and compare beta-(1,3)-glucan levels in the EDC and in floor and
      actively collected airborne dust samples of the previously performed EDC
      validation study. The EDC beta-(1,3)-glucan levels correlated moderately with
      beta-(1,3)-glucans in actively collected airborne dust and floor dust samples,
      while the glucan levels in the airborne dust and floor dust samples did not
      correlate. The combination of the newly developed beta-(1,3)-glucan sandwich EIA
      with EDC sampling now allows assessment in large-scale population studies of
      exposure to airborne beta-(1,3)-glucans in homes or other low-exposure
      environments.

PMID- 20038710
TI  - The lactococcin G immunity protein recognizes specific regions in both peptides
      constituting the two-peptide bacteriocin lactococcin G.
AB  - Lactococcin G and enterocin 1071 are two homologous two-peptide bacteriocins.
      Expression vectors containing the gene encoding the putative lactococcin G
      immunity protein (lagC) or the gene encoding the enterocin 1071 immunity protein
      (entI) were constructed and introduced into strains sensitive to one or both of
      the bacteriocins. Strains that were sensitive to lactococcin G became immune to
      lactococcin G when expressing the putative lactococcin G immunity protein,
      indicating that the lagC gene in fact encodes a protein involved in lactococcin G
      immunity. To determine which peptide or parts of the peptide(s) of each
      bacteriocin that are recognized by the cognate immunity protein, combinations of
      wild-type peptides and hybrid peptides from the two bacteriocins were assayed
      against strains expressing either of the two immunity proteins. The lactococcin G
      immunity protein rendered the enterococcus strain but not the lactococcus strains
      resistant to enterocin 1071, indicating that the functionality of the immunity
      protein depends on a cellular component. Moreover, regions important for
      recognition by the immunity protein were identified in both peptides (Lcn-alpha
      and Lcn-beta) constituting lactococcin G. These regions include the N-terminal
      end of Lcn-alpha (residues 1 to 13) and the C-terminal part of Lcn-beta (residues
      14 to 24). According to a previously proposed structural model of lactococcin G,
      these regions will be positioned adjacent to each other in the transmembrane
      helix-helix structure, and the model thus accommodates the present results.

PMID- 20038711
TI  - Inducible expression of transmembrane proteins on bacterial magnetic particles in
      Magnetospirillum magneticum AMB-1.
AB  - Bacterial magnetic particles (BacMPs) produced by the magnetotactic bacterium
      Magnetospirillum magneticum AMB-1 are used for a variety of biomedical
      applications. In particular, the lipid bilayer surrounding BacMPs has been
      reported to be amenable to the insertion of recombinant transmembrane proteins;
      however, the display of transmembrane proteins in BacMP membranes remains a
      technical challenge due to the cytotoxic effects of the proteins when they are
      overexpressed in bacterial cells. In this study, a tetracycline-inducible
      expression system was developed to display transmembrane proteins on BacMPs. The
      expression and localization of the target proteins were confirmed using
      luciferase and green fluorescent protein as reporter proteins. Gene expression
      was suppressed in the absence of anhydrotetracycline, and the level of protein
      expression could be controlled by modulating the concentration of the inducer
      molecule. This system was implemented to obtain the expression of the tetraspanin
      CD81. The truncated form of CD81 including the ligand binding site was
      successfully displayed at the surface of BacMPs by using Mms13 as an anchor
      protein and was shown to bind the hepatitis C virus envelope protein E2. These
      results suggest that the tetracycline-inducible expression system described here
      will be a useful tool for the expression and display of transmembrane proteins in
      the membranes of BacMPs.

PMID- 20038712
TI  - Effect of growth phase feeding strategies on succinate production by
      metabolically engineered Escherichia coli.
AB  - Aerobic growth conditions significantly influenced anaerobic succinate production
      in two-stage fermentation by Escherichia coli AFP111 with knockouts in rpoS,
      pflAB, ldhA, and ptsG genes. At a low cell growth rate limited by glucose,
      enzymes involved in the reductive arm of the tricarboxylic acid cycle and the
      glyoxylate shunt showed elevated activities, providing AFP111 with intracellular
      redox balance and increased succinic acid yield and productivity.

PMID- 20038713
TI  - Identification of the main promoter directing cereulide biosynthesis in emetic
      Bacillus cereus and its application for real-time monitoring of ces gene
      expression in foods.
AB  - Cereulide, the emetic Bacillus cereus toxin, is synthesized by cereulide
      synthetase via a nonribosomal peptide synthetase (NRPS) mechanism. Previous
      studies focused on the identification, structural organization, and biochemical
      characterization of the ces gene locus encoding cereulide synthetase; however,
      detailed information about the transcriptional organization of the ces genes was
      lacking. The present study shows that the cesPTABCD genes are transcribed as a 23
      kb polycistronic transcript, while cesH, encoding a putative hydrolase, is
      transcribed from its own promoter. Transcription initiation was mapped by primer
      extension and rapid amplification of cDNA ends (RACE). Deletion analysis of
      promoter elements revealed a main promoter located upstream of the cesP coding
      sequence, encoding a 4'-phosphopantetheinyl transferase. This promoter drives
      transcription of cesPTABCD. In addition, intracistronic promoter regions in
      proximity to the translational start sites of cesB and cesT were identified but
      were only weakly active under the chosen assay conditions. The identified main
      promoter was amplified from the emetic reference strain B. cereus F4810/72 and
      fused to luciferase genes in order to study promoter activity in complex
      environments and to establish a biomonitoring system to assess cereulide
      production in different types of foods. ces promoter activity was strongly
      influenced by the food matrix and varied by 5 orders of magnitude. The amount of
      cereulide toxin extracted from spiked foods correlated well with the
      bioluminescence data, thus illustrating the potential of the established reporter
      system for monitoring of ces gene expression in complex matrices.

PMID- 20038714
TI  - Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking
      defects and mitochondrial dysfunction in Parkinson's disease models.
AB  - alpha-Synuclein (alpha-syn) is a small lipid-binding protein involved in vesicle
      trafficking whose function is poorly characterized. It is of great interest to
      human biology and medicine because alpha-syn dysfunction is associated with
      several neurodegenerative disorders, including Parkinson's disease (PD). We
      previously created a yeast model of alpha-syn pathobiology, which established
      vesicle trafficking as a process that is particularly sensitive to alpha-syn
      expression. We also uncovered a core group of proteins with diverse activities
      related to alpha-syn toxicity that is conserved from yeast to mammalian neurons.
      Here, we report that a yeast strain expressing a somewhat higher level of alpha
      syn also exhibits strong defects in mitochondrial function. Unlike our previous
      strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking
      alone does not suppress alpha-syn toxicity in this strain. In an effort to
      identify individual compounds that could simultaneously rescue these apparently
      disparate pathological effects of alpha-syn, we screened a library of 115,000
      compounds. We identified a class of small molecules that reduced alpha-syn
      toxicity at micromolar concentrations in this higher toxicity strain. These
      compounds reduced the formation of alpha-syn foci, re-established ER-to-Golgi
      trafficking and ameliorated alpha-syn-mediated damage to mitochondria. They also
      corrected the toxicity of alpha-syn in nematode neurons and in primary rat
      neuronal midbrain cultures. Remarkably, the compounds also protected neurons
      against rotenone-induced toxicity, which has been used to model the mitochondrial
      defects associated with PD in humans. That single compounds are capable of
      rescuing the diverse toxicities of alpha-syn in yeast and neurons suggests that
      they are acting on deeply rooted biological processes that connect these
      toxicities and have been conserved for a billion years of eukaryotic evolution.
      Thus, it seems possible to develop novel therapeutic strategies to simultaneously
      target the multiple pathological features of PD.

PMID- 20038715
TI  - Recipient Toll-like receptors contribute to chronic graft dysfunction by both
      MyD88- and TRIF-dependent signaling.
AB  - Toll-like receptors (TLRs) recognize specific molecular patterns derived from
      microbial components (exogenous ligands) or stressed cells (endogenous ligands).
      Stimulation of these receptors leads to a pronounced inflammatory response in a
      variety of acute animal models. Chronic allograft dysfunction (CAD) was regarded
      as a candidate disease to test whether TLRs influence chronic fibrosing
      inflammation. Potential endogenous renal TLR ligands, specifically for TLR2 and
      TLR4, have now been detected by a significant upregulation of glucose regulated
      protein (GRP)-94, fibrinogen, heat shock protein (HSP)-60, HSP-70, biglycan (Bgn)
      and high-mobility group box chromosomal protein 1 (HMGB1) in the acute and
      chronic transplant setting. In a genetic approach to define the contribution of
      TLR2 and TLR4, and their adaptor proteins MyD88 and TRIF [Toll/interleukin (IL)-1
      receptor domain-containing adaptor-protein inducing interferon beta], to CAD,
      kidney transplantation of TLR wild-type grafts to recipients who were deficient
      in TLR2, TLR4, TLR2/4, MyD88 and TRIF was performed. TLR and adaptor protein
      deficiencies significantly improved the excretory function of chronic kidney
      grafts by between 65% and 290%, and histopathologic signs of chronic allograft
      damage were significantly ameliorated. T cells, dendritic cells (DCs) and
      foremost macrophages were reduced in grafts by up to 4.5-fold. The intragraft
      concentrations of IL-6, IL-10, monocyte chemotactic protein-1 (MCP-1) and IL
      12p70 were significantly lower. TLR-, MyD88- and TRIF-deficient recipients showed
      a significant reduction in fibrosis. alpha-smooth muscle actin (alpha-SMA)
      positive cells were decreased by up to ninefold, and collagen I and III were
      reduced by up to twofold. These findings highlight the functional relevance of
      TLRs and their two major signaling pathways in graft-infiltrating mononuclear
      cells in the pathophysiology of CAD. A TLR signaling blockade may be a
      therapeutic option for the prevention of CAD.

PMID- 20038716
TI  - A Drosophila model of Menkes disease reveals a role for DmATP7 in copper
      absorption and neurodevelopment.
AB  - Human Menkes disease is a lethal neurodegenerative disorder of copper metabolism
      that is caused by mutations in the ATP7A copper-transporting gene. In the present
      study, we attempted to construct a Drosophila model of Menkes disease by RNA
      interference (RNAi)-induced silencing of DmATP7, the Drosophila orthologue of
      mammalian ATP7A, in the digestive tract. Here, we show that a lowered level of
      DmATP7 mRNA in the digestive tract results in a reduced copper content in the
      head and the rest of the body of surviving adults, presumably owing to copper
      entrapment in the gut. Similar to Menkes patients, a majority of flies exhibit an
      impaired neurological development during metamorphosis and die before eclosion.
      In addition, we show that survival to the adult stage is highly dependent on the
      copper content of the food and that overexpression of the copper homeostasis
      gene, metal-responsive transcription factor-1 (MTF-1), enhances survival to the
      adulthood stage. Taken together, these results highlight the role of DmATP7
      mediated copper uptake in the neurodevelopment of Drosophila melanogaster and
      provide a framework for the analysis of potential gene interactions influencing
      Menkes disease.

PMID- 20038717
TI  - Physician preferences and knowledge gaps regarding the care of childhood cancer
      survivors: a mailed survey of pediatric oncologists.
AB  - PURPOSE Little is known about physicians' attitudes and knowledge regarding the
      health care needs of childhood cancer survivors (CCS). We sought to obtain
      pediatric cancer physicians' self-reported attitudes and knowledge regarding this
      population. METHODS A mailed survey was sent to 1,159 pediatric oncologists in
      the United States. Results A total of 655 surveys were returned (ie, 57% response
      rate). Median age of respondents was 47 years (range, 31 to 82 years); 57% were
      men. Respondents practiced for a median 14 years (range, 1 to 50 years) and
      reported seeing a median of 21 patients per week (range, 0 to 250 patients per
      week). When comfort levels in caring for CCS were described (ie, 1 = very
      uncomfortable; 7 = very comfortable), respondents were most comfortable with
      survivors < or = 21 years (mean +/- standard deviation, 6.2 +/- 1.3 level), were
      less comfortable (5.0 +/- 1.5 level) with those older than 21 years but less than
      30 years old, and were uncomfortable with CCS > or = 30 years (2.9 +/- 1.7
      level). In response to a clinical vignette of a 29-year-old woman treated with
      mantle radiation for Hodgkin's lymphoma at 16 years of age, and on the basis of
      available guidelines, 34% of respondents did not appropriately recommend yearly
      breast cancer surveillance; 43% of respondents did not appropriately recommend
      cardiac surveillance; and 24% of respondents did not appropriately recommend
      yearly thyroid surveillance. Those with greater self-reported familiarity with
      available long-term follow-up (LTFU) guidelines (odds ratio [OR], 1.33; 95% CI,
      1.15 to 1.54) and with receipt of training in the care of CCS (OR, 1.73; 95% CI,
      1.18 to 2.52) were more likely to have answered all three questions correctly.
      CONCLUSION Pediatric oncologists express a range of preferences with regard to
      LTFU of CCS. Many appear unfamiliar with LTFU surveillance guidelines.

PMID- 20038718
TI  - Sources of bias in specimens for research about molecular markers for cancer.
AB  - Claims about the diagnostic or prognostic accuracy of markers often prove
      disappointing when "discrimination" found between cancers versus normals is due
      to bias, a systematic difference between compared groups. This article describes
      a framework to help simplify and organize current problems in marker research by
      focusing on the role of specimens as a source of bias in observational research
      and using that focus to address problems and improve reliability. The central
      idea is that the "fundamental comparison" in research about markers (ie, the
      comparison done to assess whether a marker discriminates) involves two distinct
      processes that are "connected" by specimens. If subject selection (first process)
      creates baseline inequality between groups being compared, then laboratory
      analysis of specimens (second process) may erroneously find positive results.
      Although both processes are important, subject selection more fundamentally
      influences the quality of marker research, because it can hardwire bias into all
      comparisons in a way that cannot be corrected by any refinement in laboratory
      analysis. An appreciation of the separateness of these two processes-and placing
      investigators with appropriate expertise in charge of each-may increase the
      reliability of research about cancer biomarkers.

PMID- 20038719
TI  - Patterns of improved survival in patients with multiple myeloma in the twenty
      first century: a population-based study.
AB  - PURPOSE Randomized multiple myeloma (MM) studies show improved response rates and
      better progression-free survival for newer therapies. However, a less pronounced
      effect has been found for overall survival (OS). Using population-based data
      including detailed treatment information for individual patients, we assessed
      survival patterns for all patients diagnosed with MM in Malmo, Sweden from 1950
      to 2005. PATIENTS AND METHODS We identified 773 patients with MM (48% males). On
      the basis of the age limit used for treatment with high-dose melphalan with
      autologous stem-cell support (HDM-ASCT; < or = 65 years old) in Sweden, we
      constructed Kaplan-Meier curves and used the Breslow generalized Wilcoxon test to
      evaluate OS patterns (diagnosed in six calendar periods) for patients 65 years
      old or younger and patients older than 65 years. Results Including all age
      groups, patients diagnosed from 1960 to 1969 had a better survival than patients
      diagnosed from 1950 to 1959. In subsequent 10-year calendar periods, median OS
      increased from 24.3 to 56.3 months (P = .036) in patients < or = 65 years old. In
      contrast, OS did not improve among patients older than age 65 years (21.2 to 26.7
      months, P = .7). CONCLUSION With the establishment of HDM-ASCT as the standard
      therapy for younger patients with MM, OS has improved significantly for this age
      group in the general MM population. With novel therapies being commonly used at
      disease progression, presumably it becomes increasingly difficult to confirm
      survival differences between defined induction, consolidation, and maintenance
      therapies in the future. Consequently, in the era of novel MM therapies,
      population-based studies will serve as a necessary complement to randomized
      trials.

PMID- 20038720
TI  - Treatment of older patients with non-small-cell lung cancer: walking the
      therapeutic tightrope.

PMID- 20038721
TI  - Evaluation of coronary artery disease by computed tomography angiography in
      patients treated for childhood Hodgkin's lymphoma.
AB  - PURPOSE To detect pathologies in coronary arteries by computed tomography
      angiography (CTA) in survivors of childhood Hodgkin's lymphoma who have been
      treated with radiotherapy and/or cardiotoxic agents. PATIENTS AND METHODS
      Patients with HL who have been in remission for at least 2 years after completion
      of therapy were included. CBC, lipid profile, urine analysis, brain natriuretic
      peptide, troponin-T, creatinine kinase-myocardial band, ECG, telecardiography,
      echocardiography, and CTA of the patients were performed. Cardiac vascular
      abnormalities were noted. Results A total of 119 patients were included in the
      study. In 19 patients (16%), we found coronary artery abnormalities. There was a
      significant difference between the patients who received mediastinal radiotherapy
      and those who did not (P = .02). By multivariate analysis, in patients receiving
      mediastinal radiotherapy the risk of developing a coronary artery abnormality was
      found to increase 6.8 times compared with patients who did not receive
      mediastinal radiotherapy (P = .009). Stent implantation was performed in a 28
      year-old patient because of critical stenosis in right coronary. In two patients
      some irregularities were detected both in CTA and conventional angiography, and
      they remained in close follow-up. A 22-year-old patient whose CTA showed critical
      stenosis in his left anterior descending artery refused the conventional
      angiography. CONCLUSION To our knowledge, this is the first large study using CTA
      for detection of coronary abnormalities in patients treated for HL in pediatric
      age group. Coronary CTA is a minimally invasive tool for early diagnosis of
      coronary artery disease in patients who were treated with mediastinal
      radiotherapy and/or cardiotoxic chemotherapy.

PMID- 20038722
TI  - INTERESTing biomarker to select IDEAL patients for epidermal growth factor
      receptor tyrosine kinase inhibitors: yes, for EGFR mutation analysis, others, I
      PASS.

PMID- 20038723
TI  - Molecular predictors of outcome with gefitinib and docetaxel in previously
      treated non-small-cell lung cancer: data from the randomized phase III INTEREST
      trial.
AB  - PURPOSE In the phase III INTEREST trial, 1,466 pretreated patients with advanced
      non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or
      docetaxel. As a preplanned analysis, we prospectively analyzed available tumor
      biopsies to investigate the relationship between biomarkers and clinical
      outcomes. METHODS Biomarkers included epidermal growth factor receptor (EGFR)
      copy number by fluorescent in situ hybridization (374 assessable samples), EGFR
      protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS
      (n = 275) mutations. Results For all biomarker subgroups analyzed, survival was
      similar for gefitinib and docetaxel, with no statistically significant
      differences between treatments and no significant treatment by biomarker status
      interaction tests. EGFR mutation-positive patients had longer progression-free
      survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and
      higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with
      high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib
      versus docetaxel. CONCLUSION These biomarkers do not appear to be predictive
      factors for differential survival between gefitinib and docetaxel in this setting
      of previously treated patients; however, subsequent treatments may have
      influenced the survival results. For secondary end points of PFS and ORR, some
      advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and
      high EGFR copy number patients. There was no statistically significant difference
      between gefitinib and docetaxel in biomarker-negative patients. This suggests
      gefitinib can provide similar overall survival to docetaxel in patients across a
      broad range of clinical subgroups and that EGFR biomarkers such as mutation
      status may additionally identify which patients are likely to gain greatest PFS
      and ORR benefit from gefitinib.

PMID- 20038724
TI  - HER2, TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing
      chemotherapy in high-risk breast cancer patients.
AB  - PURPOSE To evaluate whether the combination of HER2 with TIMP-1 (HT) or TOP2A
      with TIMP-1 (2T) more accurately identifies patients who benefit from
      cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with
      cyclophosphamide, methotrexate, and fluorouracil (CMF) than these markers do when
      analyzed individually. PATIENTS AND METHODS The Danish Breast Cancer Cooperative
      Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer
      patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2
      negative and TIMP-1 immunoreactive tumors were classified as HT nonresponsive and
      otherwise HT responsive. Similarly, the 2T panel was constructed by combining
      TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity
      were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In
      total, 623 tumors were available for analysis, of which 154 lacked TIMP-1
      immunoreactivity, 188 were HER2 positive, and 139 had a TOP2A aberration. HT
      status was a statistically significant predictor of benefit from CEF compared
      with CMF (P(interaction) = .036 for invasive disease-free survival [IDFS] and
      .047 for overall survival [OS]). The 269 (43%) patients with a 2T-responsive
      profile had a significant reduction in IDFS events (adjusted hazard ratio, 0.48;
      95% CI, 0.34 to 0.69; P < .001) and OS events (adjusted hazard ratio, 0.54; 95%
      CI, 0.38 to 0.77; P < .001). 2T status was a highly significant predictor of
      benefit from CEF compared with CMF (P(interaction) < .0001 for IDFS and .004 for
      OS). CONCLUSION The 2T profile is a more accurate predictor of incremental
      benefit from anthracycline-containing chemotherapy than HER2, TIMP-1, or TOP2A
      individually, and compared with these, 2T classifies a larger proportion of
      patients as sensitive to anthracyclines.

PMID- 20038725
TI  - Does childhood cancer affect parental divorce rates? A population-based study.
AB  - PURPOSE Cancer in children may profoundly affect parents' personal relationships
      in terms of psychological stress and an increased care burden. This could
      hypothetically elevate divorce rates. Few studies on divorce occurrence exist, so
      the effect of childhood cancers on parental divorce rates was explored. PATIENTS
      AND METHODS Data on the entire Norwegian married population, age 17 to 69 years,
      with children age 0 to 20 years in 1974 to 2001 (N = 977,928 couples) were
      retrieved from the Cancer Registry, the Central Population Register, the
      Directorate of Taxes, and population censuses. Divorce rates for 4,590 couples
      who were parenting a child with cancer were compared with those of otherwise
      similar couples by discrete-time hazard regression models. Results Cancer in a
      child was not associated with an increased risk of parental divorce overall. An
      increased divorce rate was observed with Wilms tumor (odds ratio [OR], 1.52) but
      not with any of the other common childhood cancers. The child's age at diagnosis,
      time elapsed from diagnosis, and death from cancer did not influence divorce
      rates significantly. Increased divorce rates were observed for couples in whom
      the mothers had an education greater than high school level (OR, 1.16); the risk
      was particularly high shortly after diagnosis, for CNS cancers and Wilms tumors,
      for couples with children 0 to 9 years of age at diagnosis, and after a child's
      death. CONCLUSION This large, registry-based study shows that cancer in children
      is not associated with an increased parental divorce rate, except with Wilms
      tumors. Couples in whom the wife is highly educated appear to face increased
      divorce rates after a child's cancer, and this may warrant additional study.

PMID- 20038726
TI  - Adverse events among the elderly receiving chemotherapy for advanced non-small
      cell lung cancer.
AB  - PURPOSE: To describe chemotherapy use and adverse events (AEs) for advanced
      stage, non-small-cell lung cancer (NSCLC) in community practice, including
      descriptions according to variation by age. METHODS: We interviewed patients with
      newly diagnosed, stages IIIB and IV NSCLC in the population-based cohort studied
      by the Cancer Care Outcomes Research and Surveillance Consortium, and we
      abstracted the patient medical records. AEs were medical events occurring during
      chemotherapy. Using logistic regression, we assessed the association between age
      and chemotherapy; with Poisson regression, we estimated event rate ratios and
      adjusted the analysis for age, sex, ethnicity, radiation therapy, stage,
      histology, and presence and grade of 27 comorbidities. RESULTS: Of 1,371
      patients, 58% (95% CI, 55% to 61%) received chemotherapy and 35% (95% CI, 32% to
      38%) had AEs. After adjustment, 72% (95% CI, 65% to 79%) of those younger than 55
      years and 47% (95% CI, 42% to 52%) of those age 75 years and older received
      chemotherapy. Platinum-based therapies were less common in the older-age groups.
      Pretreatment medical event rates were 18.6% for patients younger than 55 years
      and were only 9.2% for those age 75 years and older (adjusted rate ratio, 0.49;
      95% CI, 0.26 to 0.91). In contrast, older adults were more likely to have AEs
      during chemotherapy. The adjusted rate ratios compared with age younger than 55
      years were 1.70 for 65- to 74-year-olds (95% CI, 1.19 to 2.43) and 1.34 for those
      age 75 years and older (95% CI, 0.90 to 2.00). CONCLUSION: Older patients who
      received chemotherapy had fewer pretherapy events than younger patients and were
      less likely to receive platinum-based regimens. Nevertheless, older patients had
      more adverse events during chemotherapy, independent of comorbidity. Potential
      implicit trade-offs between symptom management and treatment toxicity should be
      made explicit and additionally studied.

PMID- 20038727
TI  - Genotype-driven phase I study of irinotecan administered in combination with
      fluorouracil/leucovorin in patients with metastatic colorectal cancer.
AB  - PURPOSE We aimed to identify the maximum-tolerated dose (MTD) of irinotecan in
      patients with cancer with UGT1A1*1/*1 and *1/*28 genotypes. We hypothesize that
      the patients without the *28/*28 genotype tolerate higher doses of irinotecan.
      PATIENTS AND METHODS Patients undergoing first-line treatment for metastatic
      colorectal cancer (CRC) eligible for treatment with irinotecan plus infusional
      fluorouracil/leucovorin (FOLFIRI) were screened for the UGT1A1*28/*28 genotype
      and excluded from the study. Fifty-nine white patients with either the *1/*1 or
      the *1/*28 genotype were eligible for dose escalation of irinotecan. The starting
      dose of biweekly irinotecan was 215 mg/m(2) for both genotype groups, whereas the
      dose of infusional fluorouracil was fixed. Pharmacokinetic data of irinotecan and
      metabolites were also obtained. Results The dose of irinotecan was escalated to
      370 mg/m(2) in patients with the *1/*28 genotype and to 420 mg/m(2) in those with
      the *1/*1 genotype. Dose-limiting toxicities (DLTs) were observed in two of four
      of *1/*28 patients at 370 mg/m(2) and in two of three of *1/*1 patients at 420
      mg/m(2). No DLTs were observed in 10 *1/*28 patients at 310 mg/m(2) and in 10
      *1/*1 patients at 370 mg/m(2); hence these dose levels were the MTD for each
      genotype group. The most common grade 3 to 4 toxicities were neutropenia and
      diarrhea. The pharmacokinetics of irinotecan and SN-38 exhibit linear kinetics.
      CONCLUSION The recommended dose of 180 mg/m(2) for irinotecan in FOLFIRI is
      considerably lower than the dose that can be tolerated when patients with the
      UGT1A1*28/*28 genotype are excluded. Prospective genotype-driven studies should
      test the efficacy of higher irinotecan doses in the FOLFIRI schedule.

PMID- 20038728
TI  - Acupuncture versus venlafaxine for the management of vasomotor symptoms in
      patients with hormone receptor-positive breast cancer: a randomized controlled
      trial.
AB  - PURPOSE: Vasomotor symptoms are common adverse effects of antiestrogen hormone
      treatment in conventional breast cancer care. Hormone replacement therapy is
      contraindicated in patients with breast cancer. Venlafaxine (Effexor), the
      therapy of choice for these symptoms, has numerous adverse effects. Recent
      studies suggest acupuncture may be effective in reducing vasomotor symptoms in
      menopausal women. This randomized controlled trial tested whether acupuncture
      reduces vasomotor symptoms and produces fewer adverse effects than venlafaxine.
      PATIENTS AND METHODS: Fifty patients were randomly assigned to receive 12 weeks
      of acupuncture (n = 25) or venlafaxine (n = 25) treatment. Health outcomes were
      measured for up to 1 year post-treatment. RESULTS: Both groups exhibited
      significant decreases in hot flashes, depressive symptoms, and other quality-of
      life symptoms, including significant improvements in mental health from pre- to
      post-treatment. These changes were similar in both groups, indicating that
      acupuncture was as effective as venlafaxine. By 2 weeks post-treatment, the
      venlafaxine group experienced significant increases in hot flashes, whereas hot
      flashes in the acupuncture group remained at low levels. The venlafaxine group
      experienced 18 incidences of adverse effects (eg, nausea, dry mouth, dizziness,
      anxiety), whereas the acupuncture group experienced no negative adverse effects.
      Acupuncture had the additional benefit of increased sex drive in some women, and
      most reported an improvement in their energy, clarity of thought, and sense of
      well-being. CONCLUSION: Acupuncture appears to be equivalent to drug therapy in
      these patients. It is a safe, effective and durable treatment for vasomotor
      symptoms secondary to long-term antiestrogen hormone use in patients with breast
      cancer.

PMID- 20038729
TI  - DNA methylation predicts survival and response to therapy in patients with
      myelodysplastic syndromes.
AB  - PURPOSE: The current classification systems of myelodysplastic syndromes (MDS),
      including the International Prognostic Scoring System (IPSS), do not fully
      reflect the molecular heterogeneity of the disease. Molecular characterization
      may predict clinical outcome and help stratify patients for targeted therapies.
      Epigenetic therapy using decitabine, a DNA hypomethylating agent, is clinically
      effective for the treatment of MDS. Therefore, we investigated the association
      between DNA methylation and clinical outcome in MDS. PATIENTS AND METHODS: We
      screened 24 patients with MDS for promoter CpG island methylation of 24 genes and
      identified aberrant hypermethylation at 10 genes. We then performed quantitative
      methylation analyses by bisulfite pyrosequencing of the identified genes in 317
      patient samples from three independent studies and assessed relations between
      methylation and clinical outcome. RESULTS: In an initial training cohort of 89
      patients with MDS, methylation frequencies of individual genes ranged from 7% to
      70% and were highly concordant. Therefore, we defined a methylation z score based
      on all genes for each patient. We found that patients with higher levels of
      methylation, compared with patients with lower levels, had a shorter median
      overall survival (12.3 v 17.5 months, respectively; P = .04) and shorter median
      progression-free survival (6.4 v 14.9 months, respectively; P = .009). This
      methylation prognostic model was independent of age, sex, and IPSS group. Applied
      to two validation cohorts (228 patients), this model was confirmed as an
      independent prognostic predictor for survival. Although methylation at baseline
      did not correlate with clinical response to decitabine, we observed a significant
      correlation between reduced methylation over time and clinical responses.
      CONCLUSION: DNA methylation predicts overall and progression-free survival in
      MDS.

PMID- 20038730
TI  - Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib
      compared with continued platinum-doublet chemotherapy in Japanese patients with
      advanced non-small-cell lung cancer: results of a west Japan thoracic oncology
      group trial (WJTOG0203).
AB  - PURPOSE Gefitinib is a small molecule inhibitor of the epidermal growth factor
      receptor tyrosine kinase. We conducted a phase III trial to evaluate whether
      gefitinib improves survival as sequential therapy after platinum-doublet
      chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS Chemotherapy-naive patients with advanced stage (IIIB/IV)
      NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and
      adequate organ function were randomly assigned to either platinum-doublet
      chemotherapy up to six cycles (arm A) or platinum-doublet chemotherapy for three
      cycles followed by gefitinib 250 mg orally once daily, until disease progression
      (arm B). Patients were stratified by disease stage, sex, histology, and
      chemotherapy regimens. The primary end point was overall survival; secondary end
      points included progression-free survival, tumor response, safety, and quality of
      life. Results Between March 2003 and May 2005, 604 patients were randomly
      assigned. There was a statistically significant improvement in progression-free
      survival in arm B (hazard ratio [HR], 0.68; 95% CI, 0.57 to 0.80; P < .001);
      however, overall survival results did not reach statistical significance (HR,
      0.86; 95% CI, 0.72 to 1.03; P = .11). In an exploratory subset analysis of
      overall survival by histologic group, patients in arm B with adenocarcinoma did
      significantly better than patients in arm A with adenocarcinoma (n = 467; HR,
      0.79; 95% CI, 0.65 to 0.98; P = .03). CONCLUSION This trial failed to meet the
      primary end point of OS in patients with NSCLC. The exploratory subset analyses
      demonstrate a possible survival prolongation for sequential therapy of gefitinib,
      especially for patients with adenocarcinoma.

PMID- 20038731
TI  - Single nucleotide polymorphism in the mutational hotspot of WT1 predicts a
      favorable outcome in patients with cytogenetically normal acute myeloid leukemia.
AB  - PURPOSE: We assessed the prognostic impact of a known single nucleotide
      polymorphism (SNP) located in the mutational hotspot of WT1 in patients with
      cytogenetically normal acute myeloid leukemia (CN-AML) in the context of other
      prognostic markers. PATIENTS AND METHODS: WT1 exons 7 and 9 from 249 CN-AML
      patients from multicenter treatment trials AML-SHG Hannover 0199 (Clinical Trials
      Identifier NCT00209833) and 0295, and 50 healthy volunteers were analyzed by
      direct sequencing. NPM1, FLT3, CEBPA, and MLL were assessed for mutations and WT1
      expression was quantified. RESULTS: The minor allele of SNP rs16754 (WT1(AG/GG))
      was found in 25.7% of CN-AML patients' blasts and germline DNA and in 36% of
      healthy volunteers. Patient characteristics, frequencies of mutations, or WT1
      expression levels were similarly distributed between patients homozygous for the
      major allele compared with patients heterozygous or homozygous for the minor
      allele. SNP rs16754 status was an independent predictor of relapse-free survival
      (RFS; hazard ratio [HR], 0.49; 95% CI, 0.3 to 0.81; P = .005) and overall
      survival (OS; HR, 0.44; 95% CI, 0.27 to 0.74; P = .002) in multivariate analysis.
      The favorable effect of SNP rs16754 was stronger in NPM1/FLT3-ITD (internal
      tandem duplication of the FLT3 gene) high-risk patients compared with NPM1/FLT3
      ITD low-risk patients. Favorable prognosis could not be identified by any other
      known low-risk marker in half the patients with at least one minor allele (13% of
      all patients). No difference for complete remission rate, RFS, or OS was found
      between patients with or without acquired WT1 mutations. CONCLUSION: WT1 SNP
      rs16754 may be a novel independent favorable-risk marker in CN-AML patients that
      might improve risk and treatment stratification.

PMID- 20038732
TI  - Attempts to optimize induction and consolidation treatment in acute myeloid
      leukemia: results of the MRC AML12 trial.
AB  - PURPOSE: To optimize treatment for younger patients with acute myeloid leukemia
      and high-risk myelodysplastic syndrome by comparing induction options and the
      number of consolidation courses and whether consolidation should include
      transplantation. PATIENTS AND METHODS: We randomly assigned 1,658 patients
      younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus
      cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to
      daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard
      (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization
      were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992
      patients were randomly assigned between a total of four courses versus five
      courses, and 324 patients who were not good risk were randomly assigned to
      transplantation or chemotherapy as the final course. RESULTS: Complete remission
      (CR) was achieved in 74% of patients and CR without recovery was achieved in an
      additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR,
      relapse-free survival, relapse, or OS were seen between any of the induction
      randomizations except for a reduction in relapse risk (RR) on the mitoxantrone
      arm, which was offset by increased myelosuppression and deaths in CR. The
      addition of a fifth course did not improve OS and may be detrimental in older
      patients. Although transplantation reduced RR, it did not improve OS for the
      intermediate-risk group but was probably of benefit in high-risk patients.
      CONCLUSION: Several chemotherapy schedules achieved similar remission rates and
      OS. Four courses of chemotherapy are adequate, but the addition of
      transplantation as a final course does not improve OS. New agents are required to
      enhance conventional chemotherapy.

PMID- 20038733
TI  - Role of axillary clearance after a tumor-positive sentinel node in the
      administration of adjuvant therapy in early breast cancer.
AB  - PURPOSE The After Mapping of the Axilla: Radiotherapy or Surgery? (AMAROS) phase
      III study compares axillary lymph node dissection (ALND) and axillary radiation
      therapy (ART) in early breast cancer patients with tumor-positive sentinel nodes.
      In the ART arm, the extent of nodal involvement remains unknown, which could have
      implications on the administration of adjuvant therapy. In this preliminary
      analysis, we studied the influence of random assignment to ALND or ART on the
      choice for adjuvant treatment. PATIENTS AND METHODS In the first 2,000 patients
      enrolled in the AMAROS trial, we analyzed the administration of adjuvant systemic
      therapy. Multivariate analysis was used to assess variables affecting the
      administration of adjuvant chemotherapy. Adjuvant therapy was applied according
      to institutional guidelines. Results Of 2,000 patients, 566 patients had a
      positive sentinel node and were treated per random assignment. There was no
      significant difference in the administration of adjuvant systemic therapy. In the
      ALND and ART arms, 58% (175 of 300) and 61% (162 of 266) of the patients,
      respectively, received chemotherapy. Endocrine therapy was administered in 78%
      (235 of 300) of the patients in the ALND arm and in 76% (203 of 266) of the
      patients in the ART arm. Treatment arm was not a significant factor in the
      decision, and no interactions between treatment arm and other factors were
      observed. Multivariate analysis showed that age, tumor grade, multifocality, and
      size of the sentinel node metastasis significantly affected the administration of
      chemotherapy. Within the ALND arm, the extent of nodal involvement remained not
      significant in a sensitivity multivariate analysis. CONCLUSION Absence of
      knowledge regarding the extent of nodal involvement in the ART arm appears to
      have no major impact on the administration of adjuvant therapy.

PMID- 20038734
TI  - Randomized phase II trial of first-line trastuzumab plus docetaxel and
      capecitabine compared with trastuzumab plus docetaxel in HER2-positive metastatic
      breast cancer.
AB  - PURPOSE To evaluate trastuzumab (H) and docetaxel (T) with or without
      capecitabine (X) as first-line combination therapy for human epidermal growth
      factor receptor 2 (HER2) -positive advanced breast cancer. PATIENTS AND METHODS
      Patients with HER2-positive locally advanced or metastatic breast cancer were
      randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75
      mg/m(2) in HTX arm, 100 mg/m(2) in HT arm, every 3 weeks) with or without X (950
      mg/m(2) twice per day on days 1 to 14 every 3 weeks). The primary end point was
      overall response rate (ORR). Results In 222 patients, median follow-up was
      approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7%
      with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4%
      with HT. HTX demonstrated significantly longer progression-free survival: median
      17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045),
      which translates to a gain of around 5 months. Two-year survival probability was
      75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade
      3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment
      related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%)
      occurred more commonly with HTX than HT. One case of congestive heart failure
      occurred in each arm. CONCLUSION HTX is an effective and feasible first-line
      therapy for HER2-positive locally advanced or metastatic breast cancer, although
      it should be reserved for patients with good performance status who are not
      receiving long-term steroids.

PMID- 20038735
TI  - Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype
      represents a distinct genetic entity associated with a favorable clinical
      outcome.
AB  - PURPOSE: CEBPA mutations are found as either biallelic (biCEBPA) or monoallelic
      (moCEBPA). We set out to explore whether the kind of CEBPA mutation is of
      prognostic relevance in cytogenetically normal (CN) acute myeloid leukemia (AML).
      PATIENTS AND METHODS: Four hundred sixty-seven homogeneously treated patients
      with CN-AML were subdivided into moCEBPA, biCEBPA, and wild-type (wt) CEBPA
      patients. The subgroups were analyzed for clinical parameters and for additional
      mutations in the NPM1, FLT3, and MLL genes. Furthermore, we obtained gene
      expression profiles using oligonucleotide microarrays. RESULTS: Only patients
      with biCEBPA had an improved median overall survival when compared with patients
      with wtCEBPA (not reached v 20.4 months, respectively; P = .018), whereas
      patients with moCEBPA (20.9 months) and wtCEBPA had a similar outcome (P = .506).
      Multivariable analysis confirmed biCEBPA, but not moCEBPA, mutations as an
      independent favorable prognostic factor. Interestingly, biCEBPA mutations,
      compared with wtCEBPA, were never associated with mutated NPM1 (0% v 43%,
      respectively; P < .001) and rarely associated with FLT3 internal tandem
      duplication (ITD; 5% v 23%, respectively; P = .059), whereas patients with
      moCEBPA had a similar frequency of mutated NPM1 and a significantly higher
      association with FLT3-ITD compared with patients with wtCEBPA (44% v 23%,
      respectively; P = .037). Furthermore, patients with biCEBPA showed a homogeneous
      gene expression profile that was characterized by downregulation of HOX genes,
      whereas patients with moCEBPA showed greater heterogeneity in their gene
      expression profiles. CONCLUSION: Biallelic disruption of the N and C terminus of
      CEBPA is required for the favorable clinical outcome of CEBPA-mutated patients
      and represents a distinct molecular subtype of CN-AML with a different frequency
      of associated gene mutations. These findings are of great significance for risk
      adapted therapeutic strategies in AML.

PMID- 20038736
TI  - Endoscopic placement of a novel feeding tube.
AB  - BACKGROUND: Complications of blind feeding tube (FT) placement include
      pneumothorax, pneumonia, empyema, and death. A safe and effective method of FT
      placement is desired. The Davis FT is a novel device that detachably couples to
      an ultrathin transnasal gastroscope. The objective of this study was to evaluate
      the safety and efficacy of Davis FT placement. METHODS: Fifty consecutive
      patients requiring transpyloric enteral tube feeding underwent placement of the
      Davis FT. Placement efficacy was evaluated with postplacement radiographs.
      Patient demographics, route of tube placement, use of sedation, and complications
      were abstracted. RESULTS: The Davis FT was placed successfully in 50 patients.
      The mean age of the cohort was 52 (+/- 18) years. Sixty-two percent (31/50) were
      men. The success rate of nonpulmonary placement was 100% (50/50), and the
      postpyloric success rate was 96% (48/50). IV sedation was used in 72% (36/50) of
      placements. Eighty-six percent (43/50) of tubes were placed transnasally. The
      majority (62%) of esophagogastroduodenoscopies and Davis FT placements was
      performed by a pulmonologist. Forty-four percent (22/50) of patients had an
      endotracheal tube, 20% (10/50) had a tracheotomy, and 36% (18/50) had no
      breathing tube at the time of Davis FT placement. There were no complications.
      CONCLUSIONS: Transpyloric placement of the Davis FT is safe (100%) and effective
      (96%). The tube can be placed transorally or transnasally with or without
      sedation. The data suggest that postplacement radiographs are not necessary to
      confirm placement. Pulmonologists were successful in performing EGD and Davis FT
      placement.

PMID- 20038737
TI  - Association between a silver-coated endotracheal tube and reduced mortality in
      patients with ventilator-associated pneumonia.
AB  - BACKGROUND: A silver-coated endotracheal tube (ETT) reduced the incidence of
      ventilator-associated pneumonia (VAP) compared with an uncoated ETT in the North
      American Silver-Coated Endotracheal Tube (NASCENT) study. METHODS: To evaluate
      the effect of an ETT and risk factors on mortality, we performed a retrospective
      cohort analysis in patients who developed VAP in the NASCENT study. We determined
      causes of death and VAP due to potentially multidrug-resistant bacteria (eg,
      Pseudomonas, Acinetobacter) and performed stepwise multivariate logistic
      regression with the following predefined variables: treatment group, Acute
      Physiology and Chronic Health Evaluation (APACHE) II score, continuous sedation,
      coma, COPD, emergency surgery/trauma, immunodeficiency, potentially multidrug
      resistant bacteria, and inappropriate initial antibiotics. RESULTS: The silver
      coated ETT was associated with reduced mortality in patients with VAP (silver vs
      control, 5/37 [14%] vs 20/56 [36%], P = .03), but not in those without VAP
      (228/729 [31%] vs 178/687 [26%], P = .03). The only between-group difference in
      leading causes of death was respiratory failure (silver vs control, 45/233 [19%]
      vs 22/198 [11%], P = .02). Of the VAP-related deaths, one in the silver group was
      caused by Acinetobacter sepsis. In the control group, six deaths were caused by
      sepsis and three by pneumonia; six of nine pathogens were potentially multidrug
      resistant. In multivariate analysis, the treatment group was a predictor of
      mortality (odds ratio, silver vs control, 0.28; 95% CI, 0.09-0.89; P = .03).
      APACHE II > or = 20 and inappropriate antibiotics also remained in the model (P <
      .1). CONCLUSIONS: These findings suggest that a silver-coated ETT was associated
      with reduced mortality in patients who developed VAP in the NASCENT study.
      Studies are needed to confirm these exploratory findings.

PMID- 20038738
TI  - PET scan 18F-fluorodeoxyglucose uptake and prognosis in patients with resected
      clinical stage IA non-small cell lung cancer.
AB  - OBJECTIVE: Our objective was to examine the association between (18)F
      fluorodeoxyglucose (FDG) uptake on PET scan and prognosis in patients with
      surgically treated, clinical stage IA non-small cell lung cancer (NSCLC).
      METHODS: We reviewed data collection forms and Veterans Affairs administrative
      records of 75 patients with surgically treated, stage IA NSCLC who were enrolled
      in a prospective study of PET imaging from 1999 to 2001. We used Cox proportional
      hazards analysis to examine the association between FDG uptake and survival 4
      years following enrollment. RESULTS: Most patients were men (97%), and the mean
      age was 68 +/- 9 years. Almost half of the patients (44%) had adenocarcinoma, and
      35% underwent a sublobar resection. The mean maximum standardized uptake value
      (SUVmax) was 4.9 +/- 2.5 in survivors and 7.1 +/- 3.9 in nonsurvivors (P = .045).
      Before and after adjustment for age, tumor size, histology, and type of
      resection, the hazard of death was significantly higher in patients with squamous
      cell histology (adjusted hazard ratio [HR], 4.54; 95% CI, 1.09-18.9) and those
      with higher degrees of FDG uptake (adjusted HR, 1.21 per 1 unit increment; 95%
      CI, 1.01-1.45). At a threshold value of 5 for SUVmax, 34 of 39 patients (87%)
      with low FDG uptake survived, compared with only 24 of 36 patients (67%) with
      high FDG uptake (P = .04). Visual assessment of FDG uptake was not associated
      with an increased hazard of death (HR 0.66; 95% CI, 0.19-2.29). CONCLUSIONS: High
      FDG uptake as measured by SUVmax identifies individuals with clinical stage IA
      NSCLC who are at increased risk of death following surgery. Such high-risk
      patients may be good candidates for participation in future trials of adjuvant
      therapy.

PMID- 20038740
TI  - Anthracycline cardiomyopathy is mediated by depletion of the cardiac stem cell
      pool and is rescued by restoration of progenitor cell function.
AB  - BACKGROUND: Anthracyclines are the most effective drugs available in the
      treatment of neoplastic diseases; however, they have profound consequences on the
      structure and function of the heart, which over time cause a cardiomyopathy that
      leads to congestive heart failure. METHODS AND RESULTS: Administration of
      doxorubicin in rats led to a dilated myopathy, heart failure, and death. To test
      whether the effects of doxorubicin on cardiac anatomy and function were mediated
      by alterations in cardiac progenitor cells (CPCs), these cells were exposed to
      the anthracycline, which increased the formation of reactive oxygen species and
      caused increases in DNA damage, expression of p53, telomere attrition, and
      apoptosis. Additionally, doxorubicin resulted in cell-cycle arrest at the G2/M
      transition, which led to a significant decrease in CPC growth. Doxorubicin
      elicited multiple molecular adaptations; the massive apoptotic death that
      occurred in CPCs in the presence of anthracycline imposed on the surviving CPC
      pool the activation of several pathways aimed at preservation of the primitive
      state, cell division, lineage differentiation, and repair of damaged DNA. To
      establish whether delivery of syngeneic progenitor cells opposed the progression
      of doxorubicin cardiotoxicity, enhanced green fluorescent protein-labeled CPCs
      were injected in the failing myocardium; this treatment promoted regeneration of
      cardiomyocytes and vascular structures, which improved ventricular performance
      and rate of animal survival. CONCLUSIONS: Our results raise the possibility that
      autologous CPCs can be obtained before antineoplastic drugs are given to cancer
      patients and subsequently administered to individuals who are particularly
      sensitive to the cardiotoxicity of these agents for prevention or management of
      heart failure.

PMID- 20038741
TI  - Impact of body mass index and the metabolic syndrome on the risk of
      cardiovascular disease and death in middle-aged men.
AB  - BACKGROUND: The purpose of this study was to investigate associations between
      combinations of body mass index (BMI) categories and metabolic syndrome (MetS)
      and the risk of cardiovascular disease and death in middle-aged men. METHODS AND
      RESULTS: At age 50 years, cardiovascular risk factors were assessed in 1758
      participants without diabetes in the community-based Uppsala Longitudinal Study
      of Adult Men (ULSAM). According to BMI-MetS status, they were categorized as
      normal weight (BMI <25 kg/m(2)) without MetS (National Cholesterol Education
      Program criteria; n=891), normal weight with MetS (n=64), overweight (BMI 25 to
      30 kg/m(2)) without MetS (n=582), overweight with MetS (n=125), obese (BMI >30
      kg/m(2)) without MetS (n=30), or obese with MetS (n=66). During follow-up (median
      30 years), 788 participants died, and 681 developed cardiovascular disease
      (composite of cardiovascular death or hospitalization for myocardial infarction,
      stroke, or heart failure). In Cox proportional-hazards models that adjusted for
      age, smoking, and low-density lipoprotein cholesterol, an increased risk for
      cardiovascular disease was observed in normal-weight participants with MetS
      (hazard ratio 1.63, 95% confidence interval 1.11 to 2.37), overweight
      participants without MetS (hazard ratio 1.52, 95% confidence interval 1.28 to
      1.80), overweight participants with MetS (hazard ratio 1.74, 95% confidence
      interval 1.32 to 2.30), obese participants without MetS (hazard ratio 1.95, 95%
      confidence interval 1.14 to 3.34), and obese participants with MetS (hazard ratio
      2.55, 95% confidence interval 1.81 to 3.58) compared with normal-weight
      individuals without MetS. These BMI-MetS categories significantly predicted total
      mortality rate in a similar pattern. CONCLUSIONS: Middle-aged men with MetS had
      increased risk for cardiovascular events and total death regardless of BMI status
      during more than 30 years of follow-up. In contrast to previous reports,
      overweight and obese individuals without MetS also had an increased risk. The
      present data refute the notion that overweight and obesity without MetS are
      benign conditions.

PMID- 20038742
TI  - Antihypertensive treatment and left ventricular mass reduction: the importance of
      choosing the comparator.

PMID- 20038743
TI  - Role of epithelial sodium channels in the renal myogenic response?

PMID- 20038744
TI  - Human Nedd4L rs4149601 G allele generates evolutionary new isoform I with C2
      domain.

PMID- 20038745
TI  - Relative plasma volume monitoring and blood pressure control: an overlooked
      opportunity to achieve dry weight in the hemodialysis patient.

PMID- 20038746
TI  - Protein kinase C-dependent NAD(P)H oxidase activation induced by type 1 diabetes
      in renal medullary thick ascending limb.
AB  - Type 1 diabetes provokes a protein kinase C (PKC)-dependent accumulation of
      superoxide anion in the renal medullary thick ascending limb (mTAL). We
      hypothesized that this phenomenon involves PKC-dependent NAD(P)H oxidase
      activation. The validity of this hypothesis was explored using mTAL suspensions
      prepared from rats with streptozotocin-induced diabetes and from sham (vehicle
      treated) rats. Superoxide production was 5-fold higher in mTAL suspensions from
      diabetic rats compared with suspensions from sham rats. The NAD(P)H oxidase
      inhibitor apocynin caused an 80% decrease in superoxide production by mTAL from
      diabetic rats (P<0.05 vs untreated) without altering superoxide production by
      sham mTAL. NAD(P)H oxidase activity was >2-fold higher in mTAL from diabetic rats
      than in sham mTAL (P<0.05). Pretreatment with calphostin C (broad-spectrum PKC
      inhibitor) or rottlerin (PKCdelta inhibitor) reduced NAD(P)H oxidase activity by
      approximately 80% in both groups; however, PKCalpha/beta or PKCbeta inhibition
      did not alter NAD(P)H oxidase activity in either group. Protein levels of Nox2,
      Nox4, and p47phox were significantly higher in diabetic mTAL than in mTAL from
      sham rats. In summary, elevated superoxide production by mTAL from diabetic rats
      was normalized by NAD(P)H oxidase inhibition. PKC-dependent, PKCdelta-dependent,
      and total NAD(P)H oxidase activity was greater in mTAL from diabetic rats
      compared with sham. Protein levels of Nox2, Nox4, and p47phox were increased in
      mTAL from diabetic rats. We conclude that increased superoxide production by the
      mTAL during diabetes involves a PKCdelta-dependent increase in NAD(P)H oxidase
      activity in concert with increased protein levels of catalytic and regulatory
      subunits of the enzyme.

PMID- 20038747
TI  - Increased angiotensin II in the mesometrial triangle of a transgenic rat model of
      preeclampsia.
AB  - The pregnant female human angiotensinogen (hAGN) transgenic rat mated with the
      male hrenin (hREN) transgenic rat is a model of preeclampsia with increased blood
      pressure, proteinuria, and placenta alterations of edema and necrosis. The
      reverse mating of female hRENxmale hAGN does not show preeclamptic features.
      Because the placenta is well-recognized to be a key contributor to the
      preeclamptic syndrome, our hypothesis is that local angiotensin peptide
      concentrations found in the placenta and its associated mesometrial triangle of
      the preeclamptic transgenic rat differ from the reverse mating. We characterized
      the angiotensin peptide content and the mRNA expression of hREN and hAGN of the
      mesometrial triangle and the placenta. Three groups of pregnant rats from the
      matings (Sprague-DawleyxSprague-Dawley, reverse mating, and female hAGNxmale
      hREN) were studied on day 21 of gestation. In the hAGNxhREN transgenic rat,
      angiotensin II is significantly increased in the placenta and mesometrial
      triangle vs Sprague-Dawley (24.2+/-3.9 vs 8.6+/-1.5 pg/mg protein; 27.8+/-5.5 vs
      5.6+/-1.3 pg/mg protein; P<0.05), whereas in the reverse mating angiotensin II is
      increased in the placenta (19.1+/-1.7 vs 5.6+/-1.3 pg/mg protein; P<0.05) but
      unchanged in the mesometrial triangle (4.2+/-0.2 vs 8.6+/-1.5 pg/mg protein). The
      marked contrast in the expression of angiotensin II in the mesometrial triangle
      of the preeclamptic model vs the reverse mating suggests that local angiotensin
      II generated from the maternal parts of the uteroplacental unit may play a
      critical role in preeclampsia.

PMID- 20038748
TI  - Chronic hypertension enhances presynaptic inhibition by baclofen in the nucleus
      of the solitary tract.
AB  - The selective gamma-aminobutyric acid B-subtype receptor agonist baclofen
      activates both presynaptic and postsynaptic receptors in the brain.
      Microinjection of baclofen into the nucleus of the solitary tract increases
      arterial pressure, heart rate, and sympathetic nerve discharge consistent with
      inhibition of the arterial baroreflex. The magnitude of these responses is
      enhanced in hypertension and is associated with increased postsynaptic GABA(B)
      receptor function. We tested whether a presynaptic mechanism contributes to the
      enhanced baclofen inhibition in hypertension. Whole-cell recordings of second
      order baroreceptor neurons, identified by 4-(4-(dihexadecylamino)styryl)-N
      methylpyridinium iodide labeling of aortic nerve, were obtained in brainstem
      slices from normotensive control and renal-wrap hypertensive rats. After 4 weeks,
      arterial blood pressure was 162+/-9 mm Hg in hypertensive (n=6) and 107+/-3 mm Hg
      in control rats (n=6/11; P<0.001). Baclofen reduced the amplitude of excitatory
      postsynaptic currents evoked by solitary tract stimulation and the EC(50) of this
      inhibition was greater in control (1.5+/-0.5 micromol/L; n=6) than in
      hypertensive cells (0.6+/-0.1 micromol/L; n=9; P<0.05). Baclofen (1 micromol/L)
      elicited greater inhibition on evoked response in hypertensive (58+/-6%; n=9)
      than in control cells (40+/-6%; n=8; P<0.05). Another index of presynaptic
      inhibition, the paired-pulse ratio (ratio of second to first evoked response
      amplitudes at stimulus intervals of 40 ms), was greater in hypertensive (0.60+/
      0.08; n=8) than in control cells (0.48+/-0.06; n=5; P<0.05). The results suggest
      that in renal-wrap hypertensive rats, baclofen causes an enhanced presynaptic
      inhibition of glutamate release from baroreceptor afferent terminals to second
      order neurons in the nucleus of the solitary tract. This enhanced presynaptic
      inhibition could contribute to altered baroreflex function in hypertension.

PMID- 20038749
TI  - Interleukin 17 promotes angiotensin II-induced hypertension and vascular
      dysfunction.
AB  - We have shown previously that T cells are required for the full development of
      angiotensin II-induced hypertension. However, the specific subsets of T cells
      that are important in this process are unknown. T helper 17 cells represent a
      novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17).
      We found that angiotensin II infusion increased IL-17 production from T cells and
      IL-17 protein in the aortic media. To determine the effect of IL-17 on blood
      pressure and vascular function, we studied IL-17(-/-) mice. The initial
      hypertensive response to angiotensin II infusion was similar in IL-17(-/-) and
      C57BL/6J mice. However, hypertension was not sustained in IL-17(-/-) mice,
      reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin
      II infusion. Vessels from IL-17(-/-) mice displayed preserved vascular function,
      decreased superoxide production, and reduced T-cell infiltration in response to
      angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells
      revealed that IL-17, in conjunction with tumor necrosis factor-alpha, modulated
      expression of >30 genes, including a number of inflammatory cytokines/chemokines.
      Examination of IL-17 in diabetic humans showed that serum levels of this cytokine
      were significantly increased in those with hypertension compared with
      normotensive subjects. We conclude that IL-17 is critical for the maintenance of
      angiotensin II-induced hypertension and vascular dysfunction and might be a
      therapeutic target for this widespread disease.

PMID- 20038750
TI  - Resting heart rate pattern during follow-up and mortality in hypertensive
      patients.
AB  - There is a linear relationship between resting heart rate (HR) and mortality in
      normotensive and untreated hypertensive individuals. However, it is not clear
      whether HR is a marker of increased risk in hypertensive patients on treatment.
      We investigated the relationship between HR and mortality in patients with
      hypertension. We analyzed baseline HR, final HR, and HR change during follow-up
      in patients attending the Glasgow Blood Pressure Clinic. Using a threshold of 80
      bpm, we classified patients into those who had a consistently high (high-high) or
      low (low-low) HR or patients whose HR increased (low-high) or decreased (high
      low) over time. Survival analysis was carried out using Cox proportional hazards
      models adjusted for age, sex, body mass index, smoking, rate-limiting therapy,
      systolic blood pressure, and serum cholesterol. For each beat of HR change there
      was a 1% change in mortality risk. The highest risk of an all-cause event was
      associated with patients who had increased their HR by >or=5 bpm at the end of
      follow-up (1.51 [95% CI: 1.03 to 2.20]; P=0.035). Compared with low-low patients,
      high-high patients had a 78% increase in the risk of all-cause mortality (HR:
      1.78 [95% CI: 1.31 to 2.41]; P<0.001). Cardiovascular mortality showed a similar
      pattern of results. Rate-limiting therapy did not have an independent effect on
      outcomes in this analysis. Change in HR achieved during follow-up of hypertensive
      patients is a better predictor of risk than baseline or final HR. After
      correction for rate-limiting therapy, HR remained a significant independent risk
      factor.

PMID- 20038751
TI  - Endothelial and vascular muscle PPARgamma in arterial pressure regulation:
      lessons from genetic interference and deficiency.

PMID- 20038752
TI  - Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa
      derived hyperpolarizing factors.
AB  - Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal
      gland, is identical to arachidonic acid except for 2 additional carbons on the
      carboxyl end. Adrenic acid is metabolized by cyclooxygenases, cytochrome P450s,
      and lipoxygenases; however, little is known regarding the role of adrenic acid
      and its metabolites in vascular tone. Because of its abundance in the adrenal
      gland, we investigated the role of adrenic acid in vascular tone of bovine
      adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa
      cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent
      relaxations, which were inhibited by the epoxyeicosatrienoic acid antagonist
      14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The
      large-conductance calcium-activated potassium channel blocker iberiotoxin or
      removal of the endothelium abolished these relaxations. Reverse-phase high
      pressure liquid chromatography and liquid chromatography/mass spectrometry
      isolated and identified numerous adrenic acid metabolites from zona glomerulosa
      cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In
      denuded adrenal cortical arteries, adrenic acid caused concentration-dependent
      relaxations in the presence of zona glomerulosa cells but not in their absence.
      These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid,
      and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration
      dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15
      epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic
      acid relaxations of bovine adrenal cortical arteries are mediated by endothelial
      and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid
      metabolites could function as endogenous endothelium-derived and zona glomerulosa
      derived hyperpolarizing factors in the adrenal cortex and contribute to the
      regulation of adrenal blood flow.

PMID- 20038753
TI  - Tumor necrosis factor-alpha antagonists improve aortic stiffness in patients with
      inflammatory arthropathies: a controlled study.
AB  - The chronic inflammatory state of rheumatoid arthritis and other inflammatory
      arthropathies, such as ankylosing spondylitis and psoriatic arthritis,
      contributes to the accelerated atherosclerosis associated with these conditions.
      This study evaluates the effect of treatment with tumor necrosis factor (TNF)
      alpha antagonists on arterial stiffness in patients with inflammatory
      arthropathies. A total of 60 patients with rheumatoid arthritis, ankylosing
      spondylitis, or psoriatic arthritis and clinical indication for anti-TNF-alpha
      therapy were included. Thirty-five patients started with anti-TNF-alpha therapy
      and were compared with a nontreatment group of 25 patients. Aortic stiffness
      (aortic pulse wave velocity), augmentation index, and disease activity were
      assessed at baseline and after 3 months. Aortic pulse wave velocity (mean+/-SD)
      was reduced in the treatment group but not in the control group (-0.50+/-0.78 m/s
      versus 0.05+/-0.54 m/s, respectively; P=0.002). Concomitantly, C-reactive protein
      and the disease activity score were reduced in the treatment group (-9.3+/-20.2
      mg/L [P<0.001] and -0.74+/-0.91 [P=0.004]). Augmentation index remained unchanged
      in both groups (0.1+/-7.1% versus -1.0+/-5.8%, respectively; P=0.53). In a
      multivariate linear regression model, only treatment with TNF-alpha antagonist
      and change in mean arterial pressure predicted alterations in aortic pulse wave
      velocity. In summary, anti-TNF-alpha therapy improved aortic stiffness in
      patients with inflammatory arthropathies. These findings support the idea that
      anti-inflammatory treatment has a favorable effect on cardiovascular risk in
      patients with inflammatory arthropathies.

PMID- 20038754
TI  - Relative plasma volume monitoring during hemodialysis AIDS the assessment of dry
      weight.
AB  - Among hemodialysis patients, the assessment of dry weight remains a matter of
      clinical judgment because tests to assess dry weight have not been validated. The
      objective of this study was to evaluate and validate relative plasma volume (RPV)
      monitoring as a marker of dry weight. We performed RPV monitoring using the Crit
      Line monitor at baseline and at 8 weeks in 150 patients participating in the Dry
      Weight Reduction in Hypertensive Hemodialysis Patients Trial. The intervention
      group of 100 patients had dry weight probed, whereas 50 patients served as time
      controls. RPV slopes were defined as flat when they were less than the median
      (1.33% per hour) at the baseline visit. Among predominantly (87%) black
      hemodialysis patients, we found that flat RPV slopes suggest a volume-overloaded
      state for the following reasons: (1) probing dry weight in these patients led to
      steeper slopes; (2) those with flatter slopes at baseline had greater weight
      loss; (3) both baseline RPV slopes and the intensity of weight loss were found to
      be important for subsequent change in RPV slopes; and, most importantly, (4) RPV
      slopes predicted the subsequent reduction in interdialytic ambulatory systolic
      blood pressure. Those with the flattest slopes had the greatest decline in blood
      pressure on probing dry weight. Both baseline RPV slopes and the change in RPV
      slopes were important for subsequent changes in ambulatory systolic blood
      pressure. We conclude that RPV slope monitoring is a valid method to assess dry
      weight among hypertensive hemodialysis patients.

PMID- 20038755
TI  - Peak C-reactive protein level predicts long-term outcomes in type B acute aortic
      dissection.
AB  - Acute aortic dissection (AAD) is associated with an inflammatory reaction, as
      evidenced by elevated inflammatory markers, including C-reactive protein (CRP).
      The association between the peak CRP level and long-term outcomes in type B AAD
      has not been systematically investigated. The purpose of this study was to
      investigate whether the peak CRP level during admission predicts long-term
      outcomes in type B AAD. We conducted a clinical follow-up study of type B AAD. We
      divided the study population into 4 groups according to the tertiles of peak CRP
      levels (T1: 0.60 to 9.37 mg/dL; T2: 9.61 to 14.87 mg/dL; T3: 14.90 to 32.60
      mg/dL; and unavailable peak CRP group). Multivariate Cox regression analysis was
      applied to investigate whether the tertiles of peak CRP predict adverse events
      even after adjusting for other variables. A total of 232 type B AAD patients were
      included in this analysis. The median follow-up period was 50 months. CRP reached
      its peak on day 4.5+/-1.7. Mean peak CRP values in T1, T2, and T3 were 6.4+/-2.4,
      12.0+/-1.5, and 19.5+/-4.0 mg/dL, respectively. There were 65 events (39 deaths
      and 26 aortic events) during the follow-up. T3 and T2 (versus T1) were strong
      predictors of adverse events (T3: hazard ratio: 6.02 [95% CI: 2.44 to 14.87],
      P=0.0001; T2: hazard ratio: 3.25 [95% CI: 1.37 to 7.71], P=0.01) after
      controlling for all of the confounding factors. In conclusion, peak CRP is a
      strong predictor for adverse long-term events in patients with type B AAD.

PMID- 20038756
TI  - Measurement of blood pressure in the office: recognizing the problem and
      proposing the solution.

PMID- 20038758
TI  - Interferon-beta mechanisms of action in multiple sclerosis.
AB  - ABSTRACT Multiple sclerosis (MS) is a chronic autoimmune disease of the CNS
      characterized by inflammation, demyelination, and axonal injury. These pathologic
      effects are manifested in clinical symptoms of relapse and disability. Various
      disease-modifying therapies have been developed in recent years to modulate the
      body's immune response. Among the most widely used are the beta interferons
      (IFNbeta). All produce comparable biological effects and are approved for the
      treatment of relapsing-remitting MS (RRMS). Although the precise mechanisms
      through which IFNbeta achieves its antiinflammatory and immunomodulatory effects
      remain uncertain, several modes of action have been proposed, including
      inhibition of T-cell activation and proliferation; apoptosis of autoreactive T
      cells; induction of regulatory T cells; inhibition of leukocyte migration across
      the blood-brain barrier; cytokine modulation; and potential antiviral activity.
      Endogenously produced IFNbeta in the injured brain is also now believed to
      contribute to mediation of antiinflammatory and regenerative effects. All these
      mechanisms are believed to underlie the therapeutic effect of IFNbeta in the
      treatment of RRMS.

PMID- 20038757
TI  - Therapeutic implications of the vasoprotective axis of the renin-angiotensin
      system in cardiovascular diseases.

PMID- 20038759
TI  - Multiple sclerosis immunology: The healthy immune system vs the MS immune system.
AB  - Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by
      both inflammation and axonal degeneration. The resulting demyelination and
      subsequent degeneration of axons account for the disability of patients with MS.
      Early investigations indicated that disease progression was driven by CD4(+)
      effector T cells. However, clinical therapies specifically targeting these cells
      have, for the most part, not been effective. Therefore, new areas of research in
      experimental autoimmune encephalomyelitis (the experimental model of MS) and
      human MS have identified previously unknown contributions to disease
      pathogenesis, including interleukin-17-producing T helper 17 cells, B cells,
      CD8(+) T cells, and both CD4(+) and CD8(+) T-regulatory cells. Research into the
      respective mechanisms of action of these cells has identified novel therapeutic
      targets to combat this devastating disease. This article reviews the autoimmune
      response in patients with MS compared with individuals without MS and summarizes
      the fundamental differences in the immunologic response between people with and
      without MS. Investigations into these autoimmune differences and the disruption
      of the homeostatic balance of the immune system will help guide future research
      into MS therapeutics, with particular attention to the long-term management of
      this disease.

PMID- 20038761
TI  - Monoclonal antibodies in MS: mechanisms of action.
AB  - The development of monoclonal antibodies (mAbs) presents an emerging, highly
      specific therapeutic strategy for the treatment of multiple sclerosis (MS). mAbs
      target selective molecules and have shown early promise, along with notable
      risks, in the treatment of MS and other immune-mediated diseases. The mechanism
      of action of the 4 mAbs under active investigation for MS (natalizumab,
      rituximab, alemtuzumab, and daclizumab) are reviewed, with a discussion of how
      mAb interaction with each target antigen may produce direct and indirect effects
      (proven and hypothesized) on immune cell activity, CNS-related inflammatory
      processes, and clinical outcomes.

PMID- 20038760
TI  - The mechanism of action of glatiramer acetate treatment in multiple sclerosis.
AB  - OBJECTIVE: Glatiramer acetate (formerly known as copolymer 1) is the major
      noninterferon immunomodulatory agent used in the treatment of relapsing-remitting
      multiple sclerosis. Its mechanism of action over the past 40 years has evolved
      with our understanding of the immune response. METHODS: We review the various
      mechanisms that have been proposed for this random polymer over the years, with
      emphasis on recent methods that utilize modern immunologic techniques. RESULTS:
      Studies describing processes such as immune deviation and effects on regulatory T
      cells and antigen-presenting cells are presented. CONCLUSIONS: Effects of
      glatiramer acetate on the immune response have evolved as our technical abilities
      and knowledge of the immune response itself have developed.

PMID- 20038762
TI  - Mitoxantrone and cytotoxic drugs' mechanisms of action.
AB  - Evidence has suggested that early, aggressive intervention may improve both short
      and long-term outcomes in patients with multiple sclerosis (MS). Cytotoxic
      agents may offer advantages in this setting, particularly when used as an
      induction or add-on therapy with immunomodulators. Immunosuppression is the
      mechanism of action common to all cytotoxic drugs; individual subtleties in
      immunoregulatory actions are likely of minor importance. In the United States,
      mitoxantrone is currently the only cytotoxic agent approved for the treatment of
      MS (secondary-progressive, progressive-relapsing, and worsening relapsing
      remitting forms). Therapies in phase III development include cyclophosphamide,
      mycophenolate mofetil, cladribine, and teriflunomide. All these drugs have
      exhibited efficacy in controlled clinical trials, although the degree of benefit
      with respect to MRI and clinical endpoints has varied both within and among the
      various agents. Further investigations are needed to determine whether cytotoxic
      drugs represent a substantial improvement over treatments that have a more
      targeted impact on the immune system.

PMID- 20038763
TI  - Emerging multiple sclerosis oral therapies.
AB  - Currently, patients suffering from multiple sclerosis (MS), a chronic
      demyelinating disorder of the CNS, must be injected with medication to provide
      modest relief for their symptoms. Five orally available therapies are being
      evaluated in phase II/III clinical trials. If these therapies prove safe and
      tolerable, oral compounds may improve patient endorsement and compliance.
      Fingolimod, a novel immunosuppressant, significantly lowered annual relapse rates
      in phase II/III trials. Laquinimod, an immunomodulator, reduced the cumulative
      number of active lesions at the highest dose tested (0.6 mg/d) in a phase II
      trial. Cladribine, another immunomodulator, reduced annual relapse rates by >50%
      and gadolinium-positive lesions by >70% at both doses tested in a phase III
      trial. Oral fumarate, with immunomodulatory and antioxidant properties, also
      lowered the number of lesions in a phase II trial. Finally, teriflunomide, an
      immunomodulator, significantly reduced MRI lesion activity and reduced annual
      relapse rates in a phase II trial. In this report, we weigh the beneficial
      outcomes of these compounds against their risks of adverse effects.

PMID- 20038764
TI  - Magnetic resonance imaging and treatment effects of multiple sclerosis
      therapeutics.
AB  - MRI is now an important component in the diagnosis and assessment of multiple
      sclerosis (MS). Evidence gleaned from imaging studies has changed our
      understanding of the pathophysiology and natural history of the disease and has
      enabled physicians to visualize the effects of immunomodulatory therapies. Serial
      MRI following the index CNS event has clarified the evolution of MS,
      demonstrating that a majority of patients with clinically isolated syndromes
      already have dissemination of lesions in space and, based on MRI characteristics,
      likely also in time. Imaging studies have also shown that axonal injury and brain
      atrophy occur early in the disease. MRI techniques, such as magnetic resonance
      spectroscopy and magnetization transfer imaging, that are generally not part of
      the imaging sequences obtained as part of regular care have provided additional
      insight into the degree and extent of the effect of the disease process on the
      CNS, tissue repair, and the neuroprotective effects of therapeutics. These data
      have contributed to improved clinical decision making and treatment outcomes.

PMID- 20038765
TI  - Multiple sclerosis pharmacogenomics: maximizing efficacy of therapy.
AB  - Genetic polymorphisms and variable expression of drug receptors, metabolizing
      enzymes, and transporters have been linked to interindividual differences in
      efficacy and toxicity of many Food and Drug Administration-approved therapeutic
      agents. In multiple sclerosis, the combination of heterogeneity of disease
      pathology and significant variation in clinical response to disease-modifying
      agents necessitates the definition of biomarkers that can a priori predict
      therapeutic response and define appropriate therapeutic regimens. Pharmacogenomic
      studies will directly address the question of heterogeneity by analysis of the
      correlation between different genomic variants and clinical responses to therapy.
      These studies will include longitudinal designs, maximize clinical response
      variables, include whole-genome technologies, use large patient cohorts, and
      require the development of novel mathematical algorithms designed to integrate
      the wealth of disparate data to identify modest genetic effects and interactions.

PMID- 20038766
TI  - Insights for practice: where mechanism of action meets patient management.

PMID- 20038767
TI  - The interplay between the immune and central nervous systems in neuronal injury.
AB  - Once perceived as a region of limited immune activity, the CNS is now known to be
      an important site of immune interactions. Activated T cells can infiltrate the
      blood-brain barrier where they accumulate and proliferate in response to antigen
      restimulation. These leukocytes express proinflammatory cytokines that help in
      activating microglia and other immune cells. A profound inflammatory response
      ensues, which can lead to axonal injury and demyelination. In contrast, other T
      cells can be neuroprotective. CD4(+) Th2 cells secrete anti-inflammatory
      cytokines and can elicit the production of bioactive neurotrophins from CNS glia.
      In addition, neurons themselves can contribute to immune system regulation by
      being targets of neurotoxic T cells or by altering T-cell activity, including the
      generation of regulatory T cells. The interplay between components of the immune
      system and CNS contributes both to healthy brain function and to the pathogenesis
      of neurodegenerative diseases such as multiple sclerosis.

PMID- 20038769
TI  - Vitamin D and older adults: more than just a bone problem?

PMID- 20038771
TI  - Mission: neurology(r).

PMID- 20038772
TI  - Evaluation of sudomotor function in diabetes using the dynamic sweat test.
AB  - BACKGROUND: The study of sudomotor function represents a useful tool to evaluate
      autonomic disorders. Currently available tests allow either the measurement of
      sweat output from the whole body or selected small skin locations over time, or
      quantification of the number and size of sweat drops at a fixed time after
      stimulation. We devised a dynamic sweat test (DST) that measures at the same time
      sweat gland density, distribution of active glands, and sweat rate, and applied
      it to the evaluation of sudomotor function in diabetes. METHODS: The DST was used
      to evaluate sweating in the forearm of 14 asymptomatic diabetic subjects and 14
      age- and sex-matched healthy controls. Distal leg was also tested in 7 patients
      and 7 controls. The formation of the imprint of pilocarpine-induced sweating was
      recorded by a digital video camera through a cornstarch-powdered transparent tape
      used as a contrast-enhancing device. Mean sweat output per gland and per skin
      area and sweat gland density per cm(2) were evaluated. RESULTS: We observed a
      significant reduction of sweating in diabetic subjects as compared to controls;
      sweat gland density per cm(2) (59.7 +/- 18.6 vs 83.7 +/- 17.3; p < 0.05) and mean
      sweat output (nL/min) per gland (4.7 +/- 0.7 vs 8.3 +/- 2.7; p = 0.01) and per
      skin area (261 +/- 100 vs 645 +/- 296; p = 0.01) were reduced in the lower limb.
      Values for the forearm were not significantly different from controls.
      CONCLUSIONS: Dynamic sweat test is an easy-to-perform, informative method to
      study sudomotor function. It provides the ability to detect subtle functional
      changes occurring in the early stages of diabetic neuropathy.

PMID- 20038773
TI  - Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3-negative
      patients.
AB  - OBJECTIVE: To report the characteristics of patients suspected to have cerebral
      autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. METHODS:
      Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81
      probands because CADASIL was clinically suspected. A retrospective analysis and
      comparison of clinical, familial, and neuroimaging features of patients with and
      without pathogenic mutations was performed. RESULTS: CADASIL was diagnosed in
      16/81 (20%) probands by finding a mutation leading to a cysteine substitution
      within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In
      the remaining 65 patients, no pathogenic mutation was found. Some features were
      significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in
      NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age
      of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white
      matter changes extended to the anterior temporal lobes (93 vs 45%), external
      capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%).
      The frequency of vascular risk factors was balanced between the 2 groups. No
      feature was peculiar to either group. CONCLUSIONS: Although certain clinical and
      neuroimaging features are more frequent in cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in
      NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that
      when diagnosing CADASIL, a number of patients with a cerebral disease
      phenotypically similar to CADASIL emerge. The genetic profile of these diseases
      and the full phenotypic difference with CADASIL remain to be further defined.

PMID- 20038774
TI  - Early outcomes and predictors in 260 patients with psychogenic nonepileptic
      attacks.
AB  - OBJECTIVE: To determine short-term outcome and its predictors in patients with
      psychogenic nonepileptic attacks (PNEA). METHODS: Retrospective cohort study of
      outcomes relating to attendance at follow-up, spells, use of emergency services,
      employment, and social security payments recorded at 6 and 12 months post
      diagnosis in 260 consecutive patients. RESULTS: A total of 187 patients (71.9%)
      attended at least 1 follow-up visit, and 105 patients (40.4%) attended 2. A total
      of 71/187 patients (38.0%) were spell-free at last follow-up. In contrast, 35/187
      patients (18.7%) had marked increase in spell frequency postdiagnosis. Delay to
      diagnosis had no relationship to outcome. Patients with anxiety or depression
      were 2.32 times less likely to become spell-free (p = 0.012), and patients
      drawing social security payments at baseline were 2.34 times less likely to
      become spell-free (p = 0.014), than patients without those factors. Men were 2.46
      times more likely to become spell-free than women (p = 0.016). While 93/187
      patients (49.7%) were using emergency medical services at baseline, only 29/187
      (15.5%) were using them at follow-up (p < 0.001). This was independent of whether
      or not the patient became spell-free. CONCLUSION: A substantial minority of our
      patients became spell-free with communication of the diagnosis the only
      intervention. Previous psychiatric diagnoses, social security payments, and
      gender were important predictors of outcome. Most patients stopped using
      emergency services, irrespective of whether or not spells continued. Outcomes
      other than spell frequency may be important in patients with psychogenic
      nonepileptic attacks.

PMID- 20038775
TI  - Ictal SPECT statistical parametric mapping in temporal lobe epilepsy surgery.
AB  - OBJECTIVE: Although subtraction ictal SPECT coregistered to MRI (SISCOM) is
      clinically useful in epilepsy surgery evaluation, it does not determine whether
      the ictal-interictal subtraction difference is statistically different from the
      expected random variation between 2 SPECT studies. We developed a statistical
      parametric mapping and MRI voxel-based method of analyzing ictal-interictal SPECT
      difference data (statistical ictal SPECT coregistered to MRI [STATISCOM]) and
      compared it with SISCOM. METHODS: Two serial SPECT studies were performed in 11
      healthy volunteers without epilepsy (control subjects) to measure random
      variation between serial studies from individuals. STATISCOM and SISCOM images
      from 87 consecutive patients who had ictal SPECT studies and subsequent temporal
      lobectomy were assessed by reviewers blinded to clinical data and outcome.
      RESULTS: Interobserver agreement between blinded reviewers was higher for
      STATISCOM images than for SISCOM images (kappa = 0.81 vs kappa = 0.36). STATISCOM
      identified a hyperperfusion focus in 84% of patients, SISCOM in 66% (p < 0.05).
      STATISCOM correctly localized the temporal lobe epilepsy (TLE) subtypes (mesial
      vs lateral neocortical) in 68% of patients compared with 24% by SISCOM (p =
      0.02); subgroup analysis of patients without lesions (as determined by MRI)
      showed superiority of STATISCOM (80% vs 47%; p = 0.04). Moreover, the probability
      of seizure-free outcome was higher when STATISCOM correctly localized the TLE
      subtype than when it was indeterminate (81% vs 53%; p = 0.03). CONCLUSION:
      Statistical ictal SPECT coregistered to MRI (STATISCOM) was superior to
      subtraction ictal SPECT coregistered to MRI for seizure localization before
      temporal lobe epilepsy (TLE) surgery. STATISCOM localization to the correct TLE
      subtype was prognostically important for postsurgical seizure freedom.

PMID- 20038777
TI  - Polyneuritis cranialis caused by varicella zoster virus in the absence of rash.

PMID- 20038778
TI  - Discordant clinicopathologic phenotypes in a Japanese kindred of fatal familial
      insomnia.

PMID- 20038776
TI  - In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia.
AB  - OBJECTIVE: To investigate the specificity of in vivo amyloid imaging with [(11)C]
      Pittsburgh Compound B (PIB) in Parkinson disease dementia (PDD). METHODS: We
      performed detailed neuropathologic examination for 3 individuals with PDD who had
      PIB PET imaging within 15 months of death. RESULTS: We observed elevated cortical
      uptake of [(11)C]-PIB on in vivo PET imaging in 2 of the 3 cases. At autopsy, all
      3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were
      classified as low-probability Alzheimer disease (AD) based on NIA-Reagan
      criteria. The 2 PIB-positive individuals had abundant diffuse Abeta plaques but
      only sparse neuritic plaques and intermediate neurofibrillary tangle pathology.
      The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and
      low neurofibrillary tangle burden. CONCLUSIONS: [(11)C]-Pittsburgh Compound B
      (PIB) PET is specific for fibrillar Abeta molecular pathology but not for
      pathologic diagnosis of comorbid Alzheimer disease in individuals with Parkinson
      disease dementia. The ability to specifically identify fibrillar Abeta amyloid in
      the setting of alpha-synucleinopathy makes [(11)C]-PIB PET a valuable tool for
      prospectively evaluating how the presence of Abeta amyloid influences the
      clinical course of dementia in patients with Lewy body disorders.

PMID- 20038779
TI  - Sleep-specific atrioventricular block.

PMID- 20038780
TI  - Palmocervical reflex: a hyperactive palmomental reflex?

PMID- 20038781
TI  - Botulinum toxin for diabetic neuropathic pain: a randomized double-blind
      crossover trial: botulinum toxin for neuropathic pain?

PMID- 20038782
TI  - Silent ischemic infarcts are associated with hemorrhage burden in cerebral
      amyloid angiopathy.

PMID- 20038783
TI  - Vascular smooth muscle cell dysfunction in patients with migraine.

PMID- 20038784
TI  - Senate's reform package wrapped up in time for Christmas.

PMID- 20038785
TI  - Membrane remodeling during reticulocyte maturation.
AB  - The transition of reticulocytes into erythrocytes is accompanied by extensive
      changes in the structure and properties of the plasma membrane. These changes
      include an increase in shear resistance, loss of surface area, and acquisition of
      a biconcave shape. The processes by which these changes are effected have
      remained largely undefined. Here we examine how the expression of 30 distinct
      membrane proteins and their interactions change during murine reticulocyte
      maturation. We show that tubulin and cytosolic actin are lost, whereas the
      membrane content of myosin, tropomyosin, intercellular adhesion molecule-4,
      glucose transporter-4, Na-K-ATPase, sodium/hydrogen exchanger 1, glycophorin A,
      CD47, Duffy, and Kell is reduced. The degradation of tubulin and actin is, at
      least in part, through the ubiquitin-proteasome degradation pathway. In regard to
      the protein-protein interactions, the formation of membrane-associated spectrin
      tetramers from dimers is unperturbed, whereas the interactions responsible for
      the formation of the membrane-skeletal junctions are weaker in reticulocytes, as
      is the attachment of transmembrane proteins to these structures. This weakness,
      in part, results from the elevated phosphorylation of 4.1R in reticulocytes,
      which leads to a decrease in shear resistance by reducing its interaction with
      spectrin and actin. These observations begin to unravel the mechanistic basis of
      crucial changes accompanying reticulocyte maturation.

PMID- 20038786
TI  - Perforin activates clathrin- and dynamin-dependent endocytosis, which is required
      for plasma membrane repair and delivery of granzyme B for granzyme-mediated
      apoptosis.
AB  - Cytotoxic T lymphocytes and natural killer cells destroy target cells via the
      polarized exocytosis of lytic effector proteins, perforin and granzymes, into the
      immunologic synapse. How these molecules enter target cells is not fully
      understood. It is debated whether granzymes enter via perforin pores formed at
      the plasma membrane or whether perforin and granzymes are first endocytosed and
      granzymes are then released from endosomes into the cytoplasm. We previously
      showed that perforin disruption of the plasma membrane induces a transient Ca(2+)
      flux into the target cell that triggers a wounded membrane repair response in
      which lysosomes and endosomes donate their membranes to reseal the damaged
      membrane. Here we show that perforin activates clathrin- and dynamin-dependent
      endocytosis, which removes perforin and granzymes from the plasma membrane to
      early endosomes, preserving outer membrane integrity. Inhibiting clathrin- or
      dynamin-dependent endocytosis shifts death by perforin and granzyme B from
      apoptosis to necrosis. Thus by activating endocytosis to preserve membrane
      integrity, perforin facilitates granzyme uptake and avoids the proinflammatory
      necrotic death of a membrane-damaged cell.

PMID- 20038787
TI  - Idiopathic CD4+ T-cell lymphocytopenia is associated with impaired membrane
      expression of the chemokine receptor CXCR4.
AB  - Idiopathic CD4(+) T-cell lymphocytopenia (ICL) is a rare acquired T-cell
      immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed
      opportunistic infections were investigated using extensive immunophenotyping
      analysis and functional evaluation of the chemokine receptor CXCR4. For all 6
      patients studied, a profound defect in CXCR4 expression was detected at the
      surface of CD4(+) T lymphocytes, in association with an abnormal intracellular
      accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all
      patients studied, CD4(+) T-cell chemotactic response toward CXCL12 was decreased,
      whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced
      endocytosis was impaired in ICL CD4(+) T cells. Upon in vitro addition of
      interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5
      of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12
      disappeared. Upon therapeutic administration of IL-2, CD4(+) T-cell count and
      membrane CXCR4 expression and function improved over time in 3 of 4 patients
      treated. Therefore, our data indicate that ICL is associated with defective
      surface expression of CXCR4, which may be reversed by IL-2.

PMID- 20038788
TI  - Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically
      relevant biomarker in predicting response to growth factor treatment.
AB  - Myelodysplastic syndromes (MDS) are a group of clonal disorders of the bone
      marrow characterized by peripheral cytopenias. Standard treatment in low- and
      intermediate-I-risk MDS is supportive therapy consisting of regular transfusions
      and growth factors, that is, erythropoietin (Epo) and granulocyte-colony
      stimulating factor (G-CSF). Because flow cytometric analysis of MDS bone marrow
      samples can identify clinically relevant subgroups regarding transfusion
      dependency and disease progression, we addressed the question whether flow
      cytometry (FCM) was instrumental in predicting response. In 46 patients with low-
      and intermediate-I-risk MDS that were treated with Epo/G-CSF, low Epo level and
      low transfusion need were associated with response to Epo/G-CSF. Interestingly,
      aberrant phenotype of myeloblasts identified nonresponders among patients with
      the greatest response probability according to the predictive model of Hellstrom
      Lindberg et al. Moreover, aberrant FCM of myeloblasts acted as a significant
      biomarker for treatment failure in multivariate analysis. A new predictive model
      based on the basis FCM combined with previously validated Epo levels is proposed
      defining 3 subgroups with 94%, 17%, and 11% response probability. In conclusion,
      FCM may add significantly to well-known predictive parameters in selecting MDS
      patients eligible for Epo/G-CSF treatment. This is of relevance regarding
      prevention of treatment failure.

PMID- 20038789
TI  - The yellow-red-black bladder diary: red-yellow-black is not just for wounds.
AB  - The Red-Yellow-Black (RYB) wound classification system was introduced to the US
      in the late 1980s for the purpose of simplifying wound assessment and guiding
      treatment. Although the color system was found to have limitations for wound
      care, the colors (in revised order) may be useful for a bladder diary. Colored
      pencils are used to record fluid intake and voided output. For fluid intake,
      yellow signifies nonirritants (water); red, low bladder irritants (alcoholic,
      artificially sweetened, carbonated, or citrus beverages); and black, high bladder
      irritants (caffeinated beverages). For voided output, yellow denotes continent
      voids and red, incontinent voids. Output quantity is measured using a commode
      "hat". The completed diary allows the practitioner to tabulate the colored daily
      rows and quickly assess progress weekly or monthly and provide appropriate
      treatment/advice. The YRB diary was used successfully by a 78-year old woman with
      urge incontinence without evidence of stress incontinence. Modifications to the
      YRB diary can be made when additional data need to be collected. Studies to
      evaluate optimal usage criteria of bladder diaries are needed.

PMID- 20038790
TI  - Framework for planning and conducting pilot studies.
AB  - Researchers working with partners in home care to plan a pragmatic multicenter
      community-based, randomized, controlled trial for leg ulcer compression treatment
      realized a smaller pilot study would be necessary. Because no framework for
      conducting pilot studies could be found, the authors developed a framework for
      pilot study methodology to inform the planning of such research. To this end, an
      integrative literature review was conducted, guided by an explicit search
      strategy, retrieval procedures, and appraisal process, to identify recognized
      pilot study aims, processes, and methodologies used in previously reported
      community pilot studies. Factors influencing study inclusion were recognized
      pilot study aims and purposes and a concise working definition of pilot study.
      Methodologies used in previously conducted community pilot studies were reviewed.
      Although relevant published research was limited, 11 pilot studies met the
      inclusion criteria for this review and contained suggestions to further develop
      or improve plans for larger definitive trials to enable a better fit of protocols
      within the delivery systems and scopes of practice. Pilot research processes
      could be divided into two stages: early planning and pilot trial. Direction for
      procedures and methods was gained relative to planning for an effective pilot
      study regarding eligibility, recruitment and data collection, management, and
      analysis. The results were used to develop an organizing framework for the
      authors' pilot study and named the Pilot Research Process (PReP) Framework. The
      process was instrumental in working with the authors' research team and clinical
      partners in the planning of their leg ulcer treatment pilot study. This framework
      may provide a foundation for others to analyze or develop a pilot study
      methodology in planning a large-scale study.

PMID- 20038791
TI  - "Measurement Monday": one facility's approach to standardizing skin impairment
      documentation.
AB  - Accurate, timely wound assessment and documentation is fundamental to nursing
      practice. A 2005 retrospective chart audit (N = 54) at a rural, 238-bed tertiary
      care facility in Northeastern Pennsylvania (average daily census 175 to 180)
      found that complete wound assessment documentation (including measurements) was
      lacking in 59% of patient charts. The purpose of this quality improvement
      initiative, led by the Wound Ostomy Continence Nurse (WOCN), was to evaluate and
      improve nursing assessment and documentation of impaired skin (pressure ulcers,
      skin tears, open surgical wounds, diabetic ulcers, and venous stasis ulcers). A
      review of the literature confirmed the importance of consistency, which led to
      the hospital-wide implementation of education programs and "Measurement Monday."
      Using AHCPR guidelines of care for pressure ulcers and beginning in January 2006
      all wounds were assessed and measured every Monday and the proportion of
      incomplete charts declined to 38%. Following addition of a wound documentation
      tool in 2007, the proportion of incomplete records was 14.8%. This quality
      improvement initiative improved the quality and consistency of wound
      assessment/measurement and documentation.

PMID- 20038792
TI  - Can we keep the "academic" in academic medicine? 2009 American Society for
      Clinical Investigation Presidential Address.

PMID- 20038793
TI  - FoxO1 expression in osteoblasts regulates glucose homeostasis through regulation
      of osteocalcin in mice.
AB  - Osteoblasts have recently been found to play a role in regulating glucose
      metabolism through secretion of osteocalcin. It is unknown, however, how this
      osteoblast function is regulated transcriptionally. As FoxO1 is a forkhead family
      transcription factor known to regulate several key aspects of glucose
      homeostasis, we investigated whether its expression in osteoblasts may contribute
      to its metabolic functions. Here we show that mice lacking Foxo1 only in
      osteoblasts had increased pancreatic beta cell proliferation, insulin secretion,
      and insulin sensitivity. The ability of osteoblast-specific FoxO1 deficiency to
      affect metabolic homeostasis was due to increased osteocalcin expression and
      decreased expression of Esp, a gene that encodes a protein responsible for
      decreasing the bioactivity of osteocalcin. These results indicate that FoxO1
      expression in osteoblasts contributes to FoxO1 control of glucose homeostasis and
      identify FoxO1 as a key modulator of the ability of the skeleton to function as
      an endocrine organ regulating glucose metabolism.

PMID- 20038794
TI  - IL-17 produced by neutrophils regulates IFN-gamma-mediated neutrophil migration
      in mouse kidney ischemia-reperfusion injury.
AB  - The IL-23/IL-17 and IL-12/IFN-gamma cytokine pathways have a role in chronic
      autoimmunity, which is considered mainly a dysfunction of adaptive immunity. The
      extent to which they contribute to innate immunity is, however, unknown. We used
      a mouse model of acute kidney ischemia-reperfusion injury (IRI) to test the
      hypothesis that early production of IL-23 and IL-12 following IRI activates
      downstream IL-17 and IFN-gamma signaling pathways and promotes kidney
      inflammation. Deficiency in IL-23, IL-17A, or IL-17 receptor (IL-17R) and mAb
      neutralization of CXCR2, the p19 subunit of IL-23, or IL-17A attenuated
      neutrophil infiltration in acute kidney IRI in mice. We further demonstrate that
      IL-17A produced by GR-1+ neutrophils was critical for kidney IRI in mice.
      Activation of the IL-12/IFN-gamma pathway and NKT cells by administering alpha
      galactosylceramide-primed bone marrow-derived DCs increased IFN-gamma production
      following moderate IRI in WT mice but did not exacerbate injury or enhance IFN
      gamma production in either Il17a-/- or Il17r-/- mice, which suggested that IL-17
      signaling was proximal to IFN-gamma signaling. This was confirmed by the finding
      that IFN-gamma administration reversed the protection seen in Il17a-/- mice
      subjected to IRI, whereas IL-17A failed to reverse protection in Ifng-/- mice.
      These results demonstrate that the innate immune component of kidney IRI requires
      dual activation of the IL-12/IFN-gamma and IL-23/IL-17 signaling pathways and
      that neutrophil production of IL-17A is upstream of IL-12/IFN-gamma. These
      mechanisms might contribute to reperfusion injury in other organs.

PMID- 20038795
TI  - Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular
      carcinoma by activating FAK signaling.
AB  - The epigenetic silencing of tumor suppressor genes is a crucial event during
      carcinogenesis and metastasis. Here, in a human genome-wide survey, we identified
      scavenger receptor class A, member 5 (SCARA5) as a candidate tumor suppressor
      gene located on chromosome 8p. We found that SCARA5 expression was frequently
      downregulated as a result of promoter hypermethylation and allelic imbalance and
      was associated with vascular invasion in human hepatocellular carcinoma (HCC).
      Furthermore, SCARA5 knockdown via RNAi markedly enhanced HCC cell growth in
      vitro, colony formation in soft agar, and invasiveness, tumorigenicity, and lung
      metastasis in vivo. By contrast, SCARA5 overexpression suppressed these malignant
      behaviors. Interestingly, SCARA5 was found to physically associate with focal
      adhesion kinase (FAK) and inhibit the tyrosine phosphorylation cascade of the FAK
      Src-Cas signaling pathway. Conversely, silencing SCARA5 stimulated the signaling
      pathway via increased phosphorylation of certain tyrosine residues of FAK, Src,
      and p130Cas; it was also associated with activation of MMP9, a tumor metastasis
      associated enzyme. Taken together, these data suggest that the plasma membrane
      protein SCARA5 can contribute to HCC tumorigenesis and metastasis via activation
      of the FAK signaling pathway.

PMID- 20038796
TI  - Cardiac signaling genes exhibit unexpected sequence diversity in sporadic
      cardiomyopathy, revealing HSPB7 polymorphisms associated with disease.
AB  - Sporadic heart failure is thought to have a genetic component, but the
      contributing genetic events are poorly defined. Here, we used ultra-high
      throughput resequencing of pooled DNAs to identify SNPs in 4 biologically
      relevant cardiac signaling genes, and then examined the association between
      allelic variants and incidence of sporadic heart failure in 2 large Caucasian
      populations. Resequencing of DNA pools, each containing DNA from approximately
      100 individuals, was rapid, accurate, and highly sensitive for identifying common
      and rare SNPs; it also had striking advantages in time and cost efficiencies over
      individual resequencing using conventional Sanger methods. In 2,606 individuals
      examined, we identified a total of 129 separate SNPs in the 4 cardiac signaling
      genes, including 23 nonsynonymous SNPs that we believe to be novel. Comparison of
      allele frequencies between 625 Caucasian nonaffected controls and 1,117 Caucasian
      individuals with systolic heart failure revealed 12 SNPs in the cardiovascular
      heat shock protein gene HSPB7 with greater proportional representation in the
      systolic heart failure group; all 12 SNPs were confirmed in an independent
      replication study. These SNPs were found to be in tight linkage disequilibrium,
      likely reflecting a single genetic event, but none altered amino acid sequence.
      These results establish the power and applicability of pooled resequencing for
      comparative SNP association analysis of target subgenomes in large populations
      and identify an association between multiple HSPB7 polymorphisms and heart
      failure.

PMID- 20038797
TI  - The unfolded protein response protects human tumor cells during hypoxia through
      regulation of the autophagy genes MAP1LC3B and ATG5.
AB  - Tumor hypoxia is a common microenvironmental factor that adversely influences
      tumor phenotype and treatment response. Cellular adaptation to hypoxia occurs
      through multiple mechanisms, including activation of the unfolded protein
      response (UPR). Recent reports have indicated that hypoxia activates a lysosomal
      degradation pathway known as autophagy, and here we show that the UPR enhances
      the capacity of hypoxic tumor cells to carry out autophagy, and that this
      promotes their survival. In several human cancer cell lines, hypoxia increased
      transcription of the essential autophagy genes microtubule-associated protein 1
      light chain 3beta (MAP1LC3B) and autophagy-related gene 5 (ATG5) through the
      transcription factors ATF4 and CHOP, respectively, which are regulated by PKR
      like ER kinase (PERK, also known as EIF2AK3). MAP1LC3B and ATG5 are not required
      for initiation of autophagy but mediate phagophore expansion and autophagosome
      formation. We observed that transcriptional induction of MAP1LC3B replenished
      MAP1LC3B protein that was turned over during extensive hypoxia-induced autophagy.
      Correspondingly, cells deficient in PERK signaling failed to transcriptionally
      induce MAP1LC3B and became rapidly depleted of MAP1LC3B protein during hypoxia.
      Consistent with these data, autophagy and MAP1LC3B induction occurred
      preferentially in hypoxic regions of human tumor xenografts. Furthermore,
      pharmacological inhibition of autophagy sensitized human tumor cells to hypoxia,
      reduced the fraction of viable hypoxic tumor cells, and sensitized xenografted
      human tumors to irradiation. Our data therefore demonstrate that the UPR is an
      important mediator of the hypoxic tumor microenvironment and that it contributes
      to resistance to treatment through its ability to facilitate autophagy.

PMID- 20038798
TI  - The Rho/Rac exchange factor Vav2 controls nitric oxide-dependent responses in
      mouse vascular smooth muscle cells.
AB  - The regulation of arterial contractility is essential for blood pressure control.
      The GTPase RhoA promotes vasoconstriction by modulating the cytoskeleton of
      vascular smooth muscle cells. Whether other Rho/Rac pathways contribute to blood
      pressure regulation remains unknown. By studying a hypertensive knockout mouse
      lacking the Rho/Rac activator Vav2, we have discovered a new signaling pathway
      involving Vav2, the GTPase Rac1, and the serine/threonine kinase Pak that
      contributes to nitric oxide-triggered blood vessel relaxation and normotensia.
      This pathway mediated the Pak-dependent inhibition of phosphodiesterase type 5, a
      process that favored RhoA inactivation and the subsequent depolymerization of the
      F-actin cytoskeleton in vascular smooth muscle cells. The inhibition of
      phosphodiesterase type 5 required its physical interaction with
      autophosphorylated Pak1 but, unexpectedly, occurred without detectable
      transphosphorylation events between those 2 proteins. The administration of
      phosphodiesterase type 5 inhibitors prevented the development of hypertension and
      cardiovascular disease in Vav2-deficient animals, demonstrating the involvement
      of this new pathway in blood pressure regulation. Taken together, these results
      unveil one cause of the cardiovascular phenotype of Vav2-knockout mice, identify
      a new Rac1/Pak1 signaling pathway, and provide a mechanistic framework for better
      understanding blood pressure control in physiological and pathological states.

PMID- 20038799
TI  - Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells
      to apoptosis induction.
AB  - The traditional view is that cancer cells predominately produce ATP by
      glycolysis, rather than by oxidation of energy-providing substrates.
      Mitochondrial uncoupling--the continuing reduction of oxygen without ATP
      synthesis--has recently been shown in leukemia cells to circumvent the ability of
      oxygen to inhibit glycolysis, and may promote the metabolic preference for
      glycolysis by shifting from pyruvate oxidation to fatty acid oxidation (FAO).
      Here we have demonstrated that pharmacologic inhibition of FAO with etomoxir or
      ranolazine inhibited proliferation and sensitized human leukemia cells--cultured
      alone or on bone marrow stromal cells--to apoptosis induction by ABT-737, a
      molecule that releases proapoptotic Bcl-2 proteins such as Bak from antiapoptotic
      family members. Likewise, treatment with the fatty acid synthase/lipolysis
      inhibitor orlistat also sensitized leukemia cells to ABT-737, which supports the
      notion that fatty acids promote cell survival. Mechanistically, we generated
      evidence suggesting that FAO regulates the activity of Bak-dependent
      mitochondrial permeability transition. Importantly, etomoxir decreased the number
      of quiescent leukemia progenitor cells in approximately 50% of primary human
      acute myeloid leukemia samples and, when combined with either ABT-737 or cytosine
      arabinoside, provided substantial therapeutic benefit in a murine model of
      leukemia. The results support the concept of FAO inhibitors as a therapeutic
      strategy in hematological malignancies.

PMID- 20038800
TI  - CD20 deficiency in humans results in impaired T cell-independent antibody
      responses.
AB  - CD20 was the first B cell differentiation antigen identified, and CD20-specific
      mAbs are commonly used for the treatment of B cell malignancies and autoantibody
      mediated autoimmune diseases. Despite this the role of CD20 in human B cell
      physiology has remained elusive. We describe here a juvenile patient with CD20
      deficiency due to a homozygous mutation in a splice junction of the CD20 gene
      (also known as MS4A1) that results in "cryptic" splicing and nonfunctional mRNA
      species. Analysis of this patient has led us to conclude that CD20 has a central
      role in the generation of T cell-independent (TI) antibody responses. Key
      evidence to support this conclusion was provided by the observation that although
      antigen-independent B cells developed normally in the absence of CD20 expression,
      antibody formation, particularly after vaccination with TI antigens, was strongly
      impaired in the patient. Consistent with this, TI antipolysaccharide B cell
      responses were severely impeded in CD20-deficient mice. Our study therefore
      identifies what we believe to be a novel type of humoral immunodeficiency caused
      by CD20 deficiency and characterized by normal development of antigen-independent
      B cells, along with a reduced capacity to mount proper antibody responses.

PMID- 20038801
TI  - Amelioration of emphysema in mice through lentiviral transduction of long-lived
      pulmonary alveolar macrophages.
AB  - Directed gene transfer into specific cell lineages in vivo is an attractive
      approach for both modulating gene expression and correcting inherited mutations
      such as emphysema caused by human alpha1 antitrypsin (hAAT) deficiency. However,
      somatic tissues are mainly comprised of heterogeneous, differentiated cell
      lineages that can be short lived and difficult to specifically transfect. Here,
      we describe an intratracheally instilled lentiviral system able to deliver genes
      selectively to as many as 70% of alveolar macrophages (AMs) in the mouse lung.
      Following a single in vivo lentiviral transduction, genetically tagged AMs
      persisted in lung alveoli and expressed transferred genes for the lifetime of the
      adult mouse. A prolonged macrophage lifespan, rather than precursor cell
      proliferation, accounted for the surprisingly sustained presence of transduced
      AMs. We utilized this long-lived population to achieve localized secretion of
      therapeutic levels of hAAT protein in lung epithelial lining fluid. In an
      established mouse model of emphysema, lentivirally delivered hAAT ameliorated the
      progression of emphysema, as evidenced by attenuation of increased lung
      compliance and alveolar size. After 24 weeks of sustained gene expression, no
      humoral or cellular immune responses to hAAT protein were detected. Our results
      challenge the dogma that AMs are short lived and suggest that these
      differentiated cells may be a possible target cell population for in vivo gene
      therapy applications, including the sustained correction of hAAT deficiency.

PMID- 20038802
TI  - Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in
      pressure-overloaded mouse hearts.
AB  - Atrial fibrillation (AF) is a common arrhythmia that increases the risk of stroke
      and heart failure. Here, we have shown that mast cells, key mediators of allergic
      and immune responses, are critically involved in AF pathogenesis in stressed
      mouse hearts. Pressure overload induced mast cell infiltration and fibrosis in
      the atrium and enhanced AF susceptibility following atrial burst stimulation.
      Both atrial fibrosis and AF inducibility were attenuated by stabilization of mast
      cells with cromolyn and by BM reconstitution from mast cell-deficient WBB6F1
      KitW/W-v mice. When cocultured with cardiac myocytes or fibroblasts, BM-derived
      mouse mast cells increased platelet-derived growth factor A (PDGF-A) synthesis
      and promoted cell proliferation and collagen expression in cardiac fibroblasts.
      These changes were abolished by treatment with a neutralizing antibody specific
      for PDGF alpha-receptor (PDGFR-alpha). Consistent with these data, upregulation
      of atrial Pdgfa expression in pressure-overloaded hearts was suppressed by BM
      reconstitution from WBB6F1-KitW/W-v mice. Furthermore, injection of the
      neutralizing PDGFR-alpha-specific antibody attenuated atrial fibrosis and AF
      inducibility in pressure-overloaded hearts, whereas administration of homodimer
      of PDGF-A (PDGF-AA) promoted atrial fibrosis and enhanced AF susceptibility in
      normal hearts. Our results suggest a crucial role for mast cells in AF and
      highlight a potential application of controlling the mast cell/PDGF-A axis to
      achieve upstream prevention of AF in stressed hearts.

PMID- 20038803
TI  - Cardiac fibroblasts are essential for the adaptive response of the murine heart
      to pressure overload.
AB  - Fibroblasts, which are the most numerous cell type in the heart, interact with
      cardiomyocytes in vitro and affect their function; however, they are considered
      to play a secondary role in cardiac hypertrophy and failure. Here we have shown
      that cardiac fibroblasts are essential for the protective and hypertrophic
      myocardial responses to pressure overload in vivo in mice. Haploinsufficiency of
      the transcription factor-encoding gene Kruppel-like factor 5 (Klf5) suppressed
      cardiac fibrosis and hypertrophy elicited by moderate-intensity pressure
      overload, whereas cardiomyocyte-specific Klf5 deletion did not alter the
      hypertrophic responses. By contrast, cardiac fibroblast-specific Klf5 deletion
      ameliorated cardiac hypertrophy and fibrosis, indicating that KLF5 in fibroblasts
      is important for the response to pressure overload and that cardiac fibroblasts
      are required for cardiomyocyte hypertrophy. High-intensity pressure overload
      caused severe heart failure and early death in mice with Klf5-null fibroblasts.
      KLF5 transactivated Igf1 in cardiac fibroblasts, and IGF-1 subsequently acted in
      a paracrine fashion to induce hypertrophic responses in cardiomyocytes. Igf1
      induction was essential for cardioprotective responses, as administration of a
      peptide inhibitor of IGF-1 severely exacerbated heart failure induced by high
      intensity pressure overload. Thus, cardiac fibroblasts play a pivotal role in the
      myocardial adaptive response to pressure overload, and this role is partly
      controlled by KLF5. Modulation of cardiac fibroblast function may provide a novel
      strategy for treating heart failure, with KLF5 serving as an attractive target.

PMID- 20038804
TI  - Lnk regulates integrin alphaIIbbeta3 outside-in signaling in mouse platelets,
      leading to stabilization of thrombus development in vivo.
AB  - The nature of the in vivo cellular events underlying thrombus formation mediated
      by platelet activation remains unclear because of the absence of a modality for
      analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor
      protein that inhibits thrombopoietin-mediated signaling, and as a result,
      megakaryocyte and platelet counts are elevated in Lnk-/- mice. Here we describe
      an unanticipated role for Lnk in stabilizing thrombus formation and clarify the
      activities of Lnk in platelets transduced through integrin alphaIIbbeta3-mediated
      outside-in signaling. We equalized platelet counts in wild-type and Lnk-/- mice
      by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser
      induced injury and in vivo imaging that enabled observation of single platelet
      behavior and the multiple steps in thrombus formation, we determined that Lnk is
      an essential contributor to the stabilization of developing thrombi within
      vessels. Lnk-/- platelets exhibited a reduced ability to fully spread on
      fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the
      beta3 integrin subunit, and reduced binding of Fyn to integrin alphaIIbbeta3.
      These results provide new insight into the mechanism of alphaIIbbeta3-based
      outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn,
      and integrins. Outside-in signaling modulators could represent new therapeutic
      targets for the prevention of cardiovascular events.

PMID- 20038805
TI  - Ramping up RANTES in the acute response to arterial injury.
AB  - Arterial injury results in the formation of neointimal lesions. Lack of
      resolution of the pathologic neointima leads to stenosis, tissue ischemia, and
      organ dysfunction. In this issue of the JCI, Kovacic et al. show that, in
      response to arterial injury in mice, the cytokine TNF-alpha triggers a novel
      signaling pathway involving the combinatorial action of two transcription
      factors, STAT3 and NF-kappaB (p65 subunit), in VSMCs (see the related article
      beginning on page 303). Upon activation, these factors turn on transcription of a
      potent T cell chemokine, RANTES, which selectively recruits T cells into the
      vessel wall as part of the vascular wound-healing response.

PMID- 20038806
TI  - New roles for Notch in tuberous sclerosis.
AB  - Tuberous sclerosis complex (TSC) is a dominantly inherited disease that is
      characterized by the growth of multiple benign tumors that are often difficult to
      treat. TSC is caused by mutations that inactivate the TSC1 or TSC2 genes, which
      normally function to inhibit activation of mammalian target of rapamycin
      signaling. In this issue of the JCI, two studies reported by Karbowniczek et al.
      and Ma et al. link TSC inactivation with activated Notch signaling (see the
      related articles beginning on pages 93 and 103, respectively). Using a variety of
      approaches, both studies show that inactivation of TSC leads to Notch1
      activation. Furthermore, studies in tumor cells suggest that inhibiting Notch
      slows growth of the tumor cells. Although much remains to be learned about the
      precise mechanisms by which TSC loss leads to Notch activation, the newly
      identified link of TSC to Notch provides the rationale for testing Notch
      inhibitors in TSC-associated tumors.

PMID- 20038807
TI  - Putting the brakes on BTLA in T cell-mediated cancer immunotherapy.
AB  - Attenuating coinhibitory molecules for the treatment of cancer is gaining a great
      deal of attention as a strategy for immunotherapy. The B and T lymphocyte
      attenuator (BTLA, CD272) is a novel coinhibitory molecule structurally and
      functionally related to CTLA-4 and PD-1. A study in this issue of the JCI by
      Derre et al. reveals that BTLA is expressed on virus-specific human CD8+ T cells
      but is progressively downregulated after their differentiation from a naive to
      effector phenotype (see the related article beginning on page 157). Surprisingly,
      tumor-specific human CD8+ T cells continue to express BTLA even after their
      differentiation to an effector phenotype. Remarkably, vaccination of melanoma
      patients with CpG led to BTLA downregulation on tumor-specific human CD8+ T
      cells, concomitant with restoration of their functionality. We discuss these
      findings in the context of the expanding field of cosignaling molecules and their
      implications for T cell-based therapies for cancer.

PMID- 20038808
TI  - Oxidant stress derails the cardiac connexon connection.
AB  - Connexin 43 (Cx43) is the major protein component of gap junctions that
      electrically couple cardiomyocytes at the intercalated disc. Oxidant stress,
      reduced Cx43 expression, and altered subcellular localization are present in many
      forms of structural heart disease. These changes in Cx43 lead to alterations in
      electrical conduction in the ventricle and predispose to lethal cardiac
      arrhythmias. In their study in this issue of the JCI, Smyth et al. tested the
      hypothesis that oxidant stress perturbs connexon forward trafficking along
      microtubules to gap junctions (see the related article beginning on page 266).
      Failing human ventricular myocardium exhibited a reduction in Cx43 and the
      microtubule-capping protein EB1 at intercalated discs. Oxidant stress in the
      adult mouse heart reduced N-cadherin, EB1, and Cx43 colocalization. In HeLa cells
      and neonatal mouse ventricular myocytes, peroxide exposure displaced EB1 from the
      plus ends of microtubules and altered microtubule dynamics. Mutational disruption
      of the EB1-tubulin interaction mimicked the effects of oxidant stress, including
      a reduction in surface Cx43 expression. These data provide important new
      molecular insights into the regulation of Cx43 at gap junctions and may identify
      targets for preservation of cellular coupling in the diseased heart.

PMID- 20038809
TI  - Sodium channels gone wild: resurgent current from neuronal and muscle
      channelopathies.
AB  - Voltage-dependent sodium channels are the central players in the excitability of
      neurons, cardiac muscle, and skeletal muscle. Hundreds of mutations in sodium
      channels have been associated with human disease, particularly genetic forms of
      epilepsy, arrhythmias, myotonia, and periodic paralysis. In this issue of the
      JCI, Jarecki and colleagues present evidence suggesting that many such mutations
      alter the gating of sodium channels to produce resurgent sodium current, an
      unusual form of gating in which sodium channels reopen following an action
      potential, thus promoting the firing of another action potential (see the related
      article beginning on page 369). The results of this study suggest a widespread
      pathophysiological role for this mechanism, previously described to occur
      normally in only a few types of neurons.

PMID- 20038810
TI  - Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed
      human and mouse myocardium.
AB  - Gap junctions form electrical conduits between adjacent myocardial cells,
      permitting rapid spatial passage of the excitation current essential to each
      heartbeat. Arrhythmogenic decreases in gap junction coupling are a characteristic
      of stressed, failing, and aging myocardium, but the mechanisms of decreased
      coupling are poorly understood. We previously found that microtubules bearing gap
      junction hemichannels (connexons) can deliver their cargo directly to adherens
      junctions. The specificity of this delivery requires the microtubule plus-end
      tracking protein EB1. We performed this study to investigate the hypothesis that
      the oxidative stress that accompanies acute and chronic ischemic disease perturbs
      connexon forward trafficking. We found that EB1 was displaced in ischemic human
      hearts, stressed mouse hearts, and isolated cells subjected to oxidative stress.
      As a result, we observed limited microtubule interaction with adherens junctions
      at intercalated discs and reduced connexon delivery and gap junction coupling. A
      point mutation within the tubulin-binding domain of EB1 reproduced EB1
      displacement and diminished connexon delivery, confirming that EB1 displacement
      can limit gap junction coupling. In zebrafish hearts, oxidative stress also
      reduced the membrane localization of connexin and slowed the spatial spread of
      excitation. We anticipate that protecting the microtubule-based forward delivery
      apparatus of connexons could improve cell-cell coupling and reduce ischemia
      related cardiac arrhythmias.

PMID- 20038811
TI  - BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be
      partially reversed by vaccination.
AB  - The function of antigen-specific CD8+ T cells, which may protect against both
      infectious and malignant diseases, can be impaired by ligation of their
      inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and
      programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA)
      was identified as a novel inhibitory receptor with structural and functional
      similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial
      and autoimmune T cell responses in mice, but its functions in humans are largely
      unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T
      cells differentiated from naive to effector cells, their surface expression of
      BTLA was gradually downregulated. In marked contrast, human melanoma tumor
      antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA
      in vivo and remained susceptible to functional inhibition by its ligand herpes
      virus entry mediator (HVEM). Such persistence of BTLA expression was also found
      in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous
      antitumor immune responses and after conventional peptide vaccination.
      Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led
      to progressive downregulation of BTLA in vivo and consequent resistance to BTLA
      HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human
      CD8+ cancer-specific T cells, and appropriate immunotherapy may partially
      overcome this inhibition.

PMID- 20038812
TI  - Human voltage-gated sodium channel mutations that cause inherited neuronal and
      muscle channelopathies increase resurgent sodium currents.
AB  - Inherited mutations in voltage-gated sodium channels (VGSCs; or Nav) cause many
      disorders of excitability, including epilepsy, chronic pain, myotonia, and
      cardiac arrhythmias. Understanding the functional consequences of the disease
      causing mutations is likely to provide invaluable insight into the roles that
      VGSCs play in normal and abnormal excitability. Here, we sought to test the
      hypothesis that disease-causing mutations lead to increased resurgent currents,
      unusual sodium currents that have not previously been implicated in disorders of
      excitability. We demonstrated that a paroxysmal extreme pain disorder (PEPD)
      mutation in the human peripheral neuronal sodium channel Nav1.7, a paramyotonia
      congenita (PMC) mutation in the human skeletal muscle sodium channel Nav1.4, and
      a long-QT3/SIDS mutation in the human cardiac sodium channel Nav1.5 all
      substantially increased the amplitude of resurgent sodium currents in an
      optimized adult rat-derived dorsal root ganglion neuronal expression system.
      Computer simulations indicated that resurgent currents associated with the Nav1.7
      mutation could induce high-frequency action potential firing in nociceptive
      neurons and that resurgent currents associated with the Nav1.5 mutation could
      broaden the action potential in cardiac myocytes. These effects are consistent
      with the pathophysiology associated with the respective channelopathies. Our
      results indicate that resurgent currents are associated with multiple
      channelopathies and are likely to be important contributors to neuronal and
      muscle disorders of excitability.

PMID- 20038813
TI  - Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates
      inflammation following arterial injury in mice.
AB  - Inflammation is a key component of arterial injury, with VSMC proliferation and
      neointimal formation serving as the final outcomes of this process. However, the
      acute events transpiring immediately after arterial injury that establish the
      blueprint for this inflammatory program are largely unknown. We therefore studied
      these events in mice and found that immediately following arterial injury, medial
      VSMCs upregulated Rantes in an acute manner dependent on Stat3 and NF-kappaB (p65
      subunit). This led to early T cell and macrophage recruitment, processes also
      under the regulation of the cyclin-dependent kinase inhibitor p21Cip1. Unique to
      VSMCs, Rantes production was initiated by Tnf-alpha, but not by Il-6/gp130. This
      Rantes production was dependent on the binding of a p65/Stat3 complex to NF
      kappaB-binding sites within the Rantes promoter, with shRNA knockdown of either
      Stat3 or p65 markedly attenuating Rantes production. In vivo, acute NF-kappaB and
      Stat3 activation in medial VSMCs was identified, with acute Rantes production
      after injury substantially reduced in Tnfa-/- mice compared with controls.
      Finally, we generated mice with SMC-specific conditional Stat3 deficiency and
      confirmed the Stat3 dependence of acute Rantes production by VSMCs. Together,
      these observations unify inflammatory events after vascular injury, demonstrating
      that VSMCs orchestrate the arterial inflammatory response program via acute
      Rantes production and subsequent inflammatory cell recruitment.

PMID- 20038814
TI  - Mammalian target of rapamycin regulates murine and human cell differentiation
      through STAT3/p63/Jagged/Notch cascade.
AB  - The receptor tyrosine kinase/PI3K/AKT/mammalian target of rapamycin
      (RTK/PI3K/AKT/mTOR) pathway is frequently altered in cancer, but the underlying
      mechanism leading to tumorigenesis by activated mTOR remains less clear. Here we
      show that mTOR is a positive regulator of Notch signaling in mouse and human
      cells, acting through induction of the STAT3/p63/Jagged signaling cascade.
      Furthermore, in response to differential cues from mTOR, we found that Notch
      served as a molecular switch to shift the balance between cell proliferation and
      differentiation. We determined that hyperactive mTOR signaling impaired cell
      differentiation of murine embryonic fibroblasts via potentiation of Notch
      signaling. Elevated mTOR signaling strongly correlated with enhanced Notch
      signaling in poorly differentiated but not in well-differentiated human breast
      cancers. Both human lung lymphangioleiomyomatosis (LAM) and mouse kidney tumors
      with hyperactive mTOR due to tumor suppressor TSC1 or TSC2 deficiency exhibited
      enhanced STAT3/p63/Notch signaling. Furthermore, tumorigenic potential of cells
      with uncontrolled mTOR signaling was suppressed by Notch inhibition. Our data
      therefore suggest that perturbation of cell differentiation by augmented Notch
      signaling might be responsible for the underdifferentiated phenotype displayed by
      certain tumors with an aberrantly activated RTK/PI3K/AKT/mTOR pathway.
      Additionally, the STAT3/p63/Notch axis may be a useful target for the treatment
      of cancers exhibiting hyperactive mTOR signaling.

PMID- 20038815
TI  - The evolutionarily conserved TSC/Rheb pathway activates Notch in tuberous
      sclerosis complex and Drosophila external sensory organ development.
AB  - Mutations in either of the genes encoding the tuberous sclerosis complex (TSC),
      TSC1 and TSC2, result in a multisystem tumor disorder characterized by lesions
      with unusual lineage expression patterns. How these unusual cell-fate
      determination patterns are generated is unclear. We therefore investigated the
      role of the TSC in the Drosophila external sensory organ (ESO), a classic model
      of asymmetric cell division. In normal development, the sensory organ precursor
      cell divides asymmetrically through differential regulation of Notch signaling to
      produce a pIIa and a pIIb cell. We report here that inactivation of Tsc1 and
      overexpression of the Ras homolog Rheb each resulted in duplication of the
      bristle and socket cells, progeny of the pIIa cell, and loss of the neuronal
      cell, a product of pIIb cell division. Live imaging of ESO development revealed
      this cell-fate switch occurred at the pIIa-pIIb 2-cell stage. In human
      angiomyolipomas, benign renal neoplasms often found in tuberous sclerosis
      patients, we found evidence of Notch receptor cleavage and Notch target gene
      activation. Further, an angiomyolipoma-derived cell line carrying biallelic TSC2
      mutations exhibited TSC2- and Rheb-dependent Notch activation. Finally,
      inhibition of Notch signaling using a gamma-secretase inhibitor suppressed
      proliferation of Tsc2-null rat cells in a xenograft model. Together, these data
      indicate that the TSC and Rheb regulate Notch-dependent cell-fate decision in
      Drosophila and Notch activity in mammalian cells and that Notch dysregulation may
      underlie some of the distinctive clinical and pathologic features of TSC.

PMID- 20038816
TI  - Sorafenib inhibits ERK1/2 and MCL-1(L) phosphorylation levels resulting in
      caspase-independent cell death in malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive, rapidly progressive
      malignancy without effective therapy. We evaluate sorafenib efficacy and impact
      on the cellular pro-survival machinery in vitro, efficacy of sorafenib as
      monotherapy and in combination with the naturally occurring death receptor
      agonist, TRAIL using human MPM cell lines, MSTO-211H, M30, REN, H28, H2052 and
      H2452. In vitro studies of the six MPM lines demonstrated single agent
      sensitivity to the multikinase inhibitor sorafenib and resistance to TRAIL. H28
      and H2452 demonstrated augmented apoptosis with the addition of TRAIL to
      sorafenib in vitro. Treated cell lines demonstrated sorafenib-induced rapid
      dephosphorylation of AKT followed shortly by near complete dephosphorylation of
      the constitutively phosphorylated ERK1/2. Sorafenib therapy also decreased
      phosphorylation of B-Raf and mTOR in several cell lines. Within 3 h of sorafenib
      treatment, a number of known pro-survival molecules were dephosphorylated and/or
      downregulated in expression including MCL-1(L), c-FLIP(L), survivin and cIAP(1).
      These changes and eventual cell death did not elicit significant caspase-3
      activation or PARP cleavage and pretreatment with the pan-caspase inhibitor, Z
      VAD-FMK, did not block sorafenib efficacy but did block the effect of TRAIL
      monotherapy. Pre-treatment with Z-VAD-FMK did not block the synergistic effect of
      TRAIL and sorafenib in H28. In summary, single agent treatment with sorafenib
      results in widespread inhibition of the pro-survival machinery in vitro leading
      to cell death via a primarily caspase-independent mechanism. Combining sorafenib
      therapy with TRAIL, may be useful in order to provide a more efficient death
      signal and this synergistic effect appears to be caspase-independent. Pilot in
      vivo data demonstrates promising evidence of therapeutic efficacy in human tumor
      bearing xenograft nu/nu mice. We document single agent activity of sorafenib
      against MPM, unravel novel effects of sorafenib on anti-apoptotic signaling
      mediators, and suggest the combination of sorafenib plus TRAIL as possible
      therapy for clinical testing in MPM.

PMID- 20038817
TI  - Reduced cell death, invasive and angiogenic features conferred by BRCA1
      deficiency in mammary epithelial cells transformed with H-Ras.
AB  - To investigate the role of tumor suppressors BRCA1 and p53 proteins in human
      breast tumorigenesis, we transformed immortalized human mammary epithelial cells,
      MCF10A, with or without BRCA1/p53 gene-specific knockdowns. Stable knockdown of
      BRCA1 alone in MCF10A cells led to centrosome amplification, impaired p53 protein
      stability, increased sensitivity towards DNA-damaging agents, defective
      chromosomal condensation at mitosis and elevated protein levels of cyclin D1 and
      c-myc. While over-expression of mutant H-Ras transformed MCF10A cells, depletion
      of BRCA1 dramatically enhanced the in vivo tumorigenesis that was associated with
      higher levels of VEGF, enhanced vascularization and less apoptosis in the BRCA1
      deficient Ras-transformed tumors. The Ras-transformed BRCA1-deficient tumors
      exhibited features of the epithelial-to-mesenchymal transition, appeared to
      secrete matrix metalloproteases as visualized by in vivo bio-imaging of tumors
      using fluorescent probe MMP680, and were locally metastatic to lymph nodes. Our
      results suggest that loss of BRCA1 function may contribute to the aggressiveness
      of Ras-MAPK driven human breast cancer with associated increase in levels of
      cyclin D1 and c-myc, enhanced MAPK activity, angiogenic potential & invasiveness.
      This mammary xenograft tumor model may be useful as a tool to understand human
      breast tumor angiogenesis and metastasis, as well as to test candidate
      therapeutics.

PMID- 20038818
TI  - mTOR binds to the promoters of RNA polymerase I- and III-transcribed genes.
AB  - Target of rapamycin (TOR) is a conserved regulator of gene expression from yeast
      to humans. In budding yeast, TOR is associated with ribosomal DNA (rDNA)
      promoter, which is critical for ribosome biogenesis and transfer RNA (tRNA)
      synthesis. Whether mTOR behaves similarly in mammalian cells is unknown. Here, we
      report that mTOR is detected at several different promoters in human and murine
      cells, including that of rDNA and tRNA genes. The association of mTOR with these
      promoters is regulated by growth signals and sensitive to rapamycin. Together,
      our observations suggest that mTOR is closely involved in gene regulation at the
      promoters, which is a conserved mechanism to control RNA polymerase I- and III
      dependent genes that are critical for protein synthesis and cell growth.

PMID- 20038819
TI  - Arabidopsis glutathione reductase 1 is dually targeted to peroxisomes and the
      cytosol.

PMID- 20038821
TI  - Paradoxical roles for antioxidants in tumor prevention and eradication.
AB  - Antioxidants have been shown to provide protection against carcinogens, toxic
      xenobiotics and oxidative stress. This has led to the hypothesis that the
      addition of antioxidants to cancer chemotherapeutic regimens could increase their
      efficacy while reducing the side effects often encountered during treatment. The
      work described in this study set out to test this hypothesis using two different
      chemotherapeutics, Paclitaxel and FUdR, and three different antioxidants,
      epigallocatechin gallate, phenethyl isothiocyanate and tert-butylhydroquinone.
      Experiments were carried out on two different breast carcinoma cell lines, MCF-7
      and MDA MB435S. Importantly, we did not observe an enhancement of the efficacy of
      the chemotherapeutic agents in the twelve combinations tested. In fact, for
      several combinations, simultaneous treatment with an antioxidant attenuated the
      efficacy of the chemotherapeutic agent. We also determined that the survival
      advantage provided by antioxidants is consistent with their ability to induce the
      expression of genes whose regulatory regions contain antioxidant response
      elements. Together, these findings suggest that the simultaneous use of
      antioxidants and chemotherapeutic agents has the potential to attenuate the
      efficacy of chemotherapy by inducing the expression of enzymes that can detoxify
      cytotoxic agents. In view of these findings, we suggest that the design of
      chemotherapeutic regimens that combine antioxidants with chemotherapeutic agents
      should be considered carefully before being initiated.

PMID- 20038820
TI  - The molecular pathogenesis of head and neck cancer.
AB  - Head and neck cancer arises from a series of molecular alterations progressive
      from dysplasia to carcinoma in situ, and finally invasive carcinoma. Risk factors
      associated with head and neck cancer include tobacco, alcohol and viral
      infection. There are genetic alterations in pre-cancerous cells that contribute
      to transformation. The accumulation of these alterations facilitates tumor
      development. Additionally, the tumor microenvironment enables tumor progression.
      The cooperative effect of molecular alterations in the tumor cells and
      compensatory microenvironment changes enable tumors to invade and metastasize.
      This review focuses on the genes and molecules altered during the progression of
      head and neck cancer with an emphasis on the genetic, molecular and phenotypic
      changes during the pathogenesis of head and neck cancer. Therapeutic strategies
      that target key changes in the tumor cells and/or stromal cells in the tumor
      microenvironment are discussed.

PMID- 20038824
TI  - Current world literature.

PMID- 20038822
TI  - Plant actin cytoskeleton re-modeling by plant parasitic nematodes.
AB  - The cytoskeleton is an important component of the plant's defense mechanism
      against the attack of pathogenic organisms. Plants however, are defenseless
      against parasitic root-knot and cyst nematodes and respond to the invasion by the
      development of a special feeding site that supplies the parasite with nutrients
      required for the completion of its life cycle. Recent studies of nematode
      invasion under treatment with cytoskeletal drugs and in mutant plants where
      normal functions of the cytoskeleton have been affected, demonstrate the
      importance of the cytoskeleton in the establishment of a feeding site and
      successful nematode reproduction. It appears that in the case of microfilaments,
      nematodes hijack the intracellular machinery that regulates actin dynamics and
      modulate the organization and properties of the actin filament network.
      Intervening with this process reduces the nematode infection efficiency and
      inhibits its life cycle. This discovery uncovers a new pathway that can be
      exploited for the protection of plants against nematodes.

PMID- 20038826
TI  - Blindness in neurological disease: a short overview of new therapies from
      translational research.

PMID- 20038827
TI  - Blood pressure treatment in acute ischemic stroke: a review of studies and
      recommendations.
AB  - PURPOSE OF REVIEW: Elevated blood pressure (BP) is frequent in patients with
      acute ischemic stroke. Pathophysiological data support its usefulness to maintain
      adequate perfusion of the ischemic penumba. This review article aims to summarize
      the available evidence from clinical studies that examined the prognostic role of
      BP during the acute phase of ischemic stroke and intervention studies that
      assessed the efficacy of active BP alteration. RECENT FINDINGS: We found 34
      observational studies (33,470 patients), with results being inconsistent among
      the studies; most studies reported a negative association between increased
      levels of BP and clinical outcome, whereas a few studies showed clinical
      improvement with higher BP levels, clinical deterioration with decreased BP, or
      no association at all. Similarly, the conclusions drawn by the 18 intervention
      studies included in this review (1637 patients) were also heterogeneous. Very
      recent clinical data suggest a possible beneficial effect of early treatment with
      some antihypertensives on late clinical outcome. SUMMARY: Observational and
      interventional studies of management of acute poststroke hypertension yield
      conflicting results. We discuss different explanations that may account for this
      and discuss the current guidelines and pathophysiological considerations for the
      management of acute poststroke hypertension.

PMID- 20038828
TI  - Premarket clinical evaluation of novel cardiovascular devices: quality analysis
      of premarket clinical studies submitted to the Food and Drug Administration 2000
      2007.
AB  - The quality of clinical data submitted by manufacturers to support Food and Drug
      Administration cardiovascular device premarket approval (PMA) applications varies
      widely and formal quality assessment has not been previously performed. This
      study evaluated all original cardiovascular device PMAs with Food and Drug
      Administration decisions between January 1, 2000, and December 31, 2007, to
      assess the quality of clinical investigations submitted by manufacturers.
      Effectiveness and safety end points were judged high quality if they were clearly
      defined and associated with a specific time point for analysis. Subject
      accounting was high quality if 90% or greater of the original cohort was
      accounted for at study conclusion. In total, 88 cardiovascular device PMAs (77.3%
      permanent implants), 132 clinical studies, 37,328 study subjects (age 61.0 +/-
      14.5 years, 33.9% women, 86.3% white), and 29,408 device recipients were
      analyzed. All PMAs contained clinical data. Primary effectiveness end points,
      primary safety end points, and subject accounting were deemed high quality in
      81.8%, 60.2%, and 77.3% of pivotal studies, respectively. Key cardiovascular
      comorbidities (coronary artery disease 51.1%, diabetes 36.6%, hypertension 35.2%,
      heart failure 37.5%, tobacco use 31.8%) and race (14.8%) were infrequently
      reported, and studies rarely included patients younger than 18 years of age
      (10.2% of studies). Poorly defined safety and effectiveness end points, poor
      patient accounting, and incomplete collection of important patient comorbidities
      make device safety and effectiveness assessments more challenging. Women,
      pediatric, and nonwhite populations are underrepresented in premarket
      cardiovascular clinical trials. Manufacturers, regulators, and the clinical
      community should collaborate to address these study shortcomings to ensure that
      patients are treated with reliable, safe, and clinically useful medical devices.

PMID- 20038829
TI  - Enhanced anticancer effect of gemcitabine by genistein in osteosarcoma: the role
      of Akt and nuclear factor-kappaB.
AB  - Genistein, a nontoxic flavonoid compound, has potent antitumor activity in
      various cancer cell lines. This study was designed to investigate whether
      combination therapy with gemcitabine and genistein enhances antitumor efficacy in
      osteosarcoma cell lines (MG-63 and U2OS). Our results show that significant
      reduction in cell viability and corresponding induction of apoptosis were
      observed with combination treatment in both cell lines. On the molecular level,
      we found that gemcitabine alone can activate nuclear factor kappaB (NF-kappaB) in
      osteosarcoma, suggesting the potential mechanism of acquired chemoresistance. In
      contrast, genistein reversed the cancer's resistance to gemcitabine through the
      downregulation of NF-kappaB activity and the suppression of Akt. These findings
      suggest that the combination of gemcitabine and genistein enhanced the antitumor
      efficacy by abrogating the Akt/NF-kappaB pathway. The marked ability to induce
      apoptosis with a combination of gemcitabine and genistein suggests that this
      could be a rational and novel approach for osteosarcoma preclinical and clinical
      trials.

PMID- 20038830
TI  - Anticancer activities of alkylating pyrrole-imidazole polyamides with specific
      sequence recognition.
AB  - In recent years, many diseases including cancer and hereditary and viral diseases
      have been understood at the DNA sequence level. Direct control of the expression
      level of a specific gene would provide a promising approach for knowledge-based
      therapy. N-methylpyrrole and N-methylimidazole polyamides are a new type of small
      compound that precisely bind to the minor groove of the DNA duplex in a sequence
      specific fashion and recruit alkylating agents to the target sequence. We
      designed and synthesized a series of sequence-specific alkylating Py-Im polyamide
      conjugates that selectively alkylate predetermined DNA sequences. We have shown
      that sequence-specific alkylating agents possess gene-silencing activities when
      they alkylate coding regions of template strands and show promising potency
      against human cancer cell lines and xenografts possessing human cancer cells. In
      this study, we focus on recent progress in alkylating Py-Im polyamides with
      regard to sequence specificity and biological activities, and the future
      direction of the rational molecular design of genetic switches in the post-genome
      era is described.

PMID- 20038831
TI  - Administration of cisplatin in three patients with carboplatin hypersensitivity:
      is skin testing useful?
AB  - Carboplatin is a chemotherapeutic agent approved in the first-line setting of
      numerous malignancies. Hypersensitivity to carboplatin has been reported in up to
      44% of patients receiving this antineoplastic agent, usually occurring after
      several courses of treatment. The aim of this study was to determine the
      usefulness of skin tests in ruling out cross-reaction to cisplatin to continue
      platinum-based chemotherapy in patients who are responsive to these agents. Prick
      tests and intradermal tests with a series of dilutions of carboplatin and
      cisplatin were performed on three patients who had exhibited medium and severe
      hypersensitivity reactions to carboplatin. Prick tests were negative in both the
      antineoplastic agents. Intradermal tests with carboplatin were positive in all
      three patients and negative with cisplatin. In all patients, the administration
      of cisplatin instead of carboplatin was well tolerated without the need of
      premedication. In conclusion, intradermal skin tests can be a useful tool for
      detecting a potential cross-reaction between platinum salts. It allows safe
      administration of a different platinum agent in patients who seem to benefit from
      platinum-based therapy. Discontinuation of chemotherapy, desensitization
      protocols and steroid premedication can be avoided.

PMID- 20038832
TI  - Alveolar accumulation/concentration of nitrogen during apneic oxygenation with
      arteriovenous carbon dioxide removal.
AB  - In a model of acute lung injury (ALI), previously, we have shown that apneic
      oxygenation, using an inspiratory O2 fraction (FiO2) of 1.0 combined with
      extracorporeal arteriovenous CO2 removal (AO-AVCR) maintains adequate arterial O2
      and CO2 levels for a prolonged period. However, it is important that FiO2 lower
      than 1.0 can be used to avoid possible pulmonary oxygen toxicity. In preliminary
      studies, arterial oxygenation decreased to extreme low levels, when FiO2 <1 was
      used in apneic oxygenation. We assumed that this was caused either by alveolar
      accumulation/concentration of N2 or by absorption atelectasis. In four
      anesthetized and mechanically ventilated pigs, mild lung injury was induced.
      After a lung recruitment maneuver, we initiated two 20-minute periods of AO-AVCR
      with FiO2 of 1 and 0.5, respectively. By using FiO2 = 1, PaO2 remained above 300
      mm Hg. At the end of the period, the alveolar O2 fraction (FAO2) was 0.89 (0.88
      0.89; median and ranges). With FiO2 = 0.5, PaO2 decreased 90% compared with
      baseline values and FAO2 decreased to 0.07 (0.06-0.07). No atelectasis was
      visible on computed tomography after either period, and we, therefore, conclude
      that the alveolar hypoxia was caused by the alveolar N2
      accumulation/concentration and subsequently by the O2 depletion.

PMID- 20038833
TI  - Dopamine receptor antagonists impair place conditioning after acute stress in
      rats.
AB  - An immediate and robust release of dopamine appears in the brain under an acute
      stressor, but the functional role of dopamine under stress remains elusive. We
      recently showed conditioned place preference (CPP) induced by the acute
      application of a stressor such as being placed on an elevated stand or
      immobilized in a restraint holder. This study tested whether dopamine is involved
      in such CPP. The selective dopamine D1 and D2 receptor antagonists, SCH23390 and
      raclopride, respectively, were injected before stressor manipulation. The doses
      of SCH23390 (0.025 and 0.05 mg/kg) and raclopride (0.05 and 0.1 mg/kg) used to
      test for stressor-induced CPP were verified to be ineffective on spontaneous
      locomotor activity. The results showed that both drugs attenuated the development
      of stressor-induced CPP. Such a CPP blocking effect by pretreatment of dopamine
      receptor antagonist was true for either kind of stressor manipulated. These
      findings indicate that an acute stressor can facilitate a follow-up place
      conditioning, and that dopamine is involved in the present type of CPP formation.

PMID- 20038834
TI  - Notch1 signaling related hippocampal neurogenesis in adult poststroke depression
      rats: a valid index for an efficient combined citalopram and WAY100635
      pharmacotherapy.
AB  - We investigated the hypothesis that hippocampal neurogenesis related to Notch1
      signaling could be a valid index for a combined citalopram and WAY100635
      pharmacotherapy for the treatment of depression arising after stroke. Adult rats
      were exposed to a chronic mild stress paradigm after ischemic surgery. Behavioral
      tests included the open-field test and a sucrose consumption test. Proliferating
      cells in the hippocampus ipsilateral to ischemia and their fate were monitored by
      bromodeoxyuridine labeling and confocal laser scanning microscopy for up to 28
      days (day 28) after ischemia. Expression of the Notch1 signaling cascade,
      including its ligand and downstream target genes, was also examined. WAY100635
      shortened the onset of citalopram action to less than the day 21 required with
      citalopram alone and also proved more effective. The activity of the Notch1
      signaling pathway in the hippocampus fluctuated in its function in proliferation
      (day 21) and differentiation (day 28) of newly formed cells in animals receiving
      the combination treatment. This indicated that augmentation of citalopram by
      cotreatment with a selective 5-hydroxytryptamine 1A antagonist would be an
      efficacious strategy for poststroke depression. The observed effects are most
      likely because of enhanced poststroke neurogenesis mediated by the Notch1
      signaling cascade.

PMID- 20038835
TI  - Peri, pre and postnatal morphine exposure: exposure-induced effects and sex
      differences in the behavioural consequences in rat offspring.
AB  - This study investigated the behavioural consequences of peri, pre and postnatal
      morphine (MO) exposure in rats. From gestational day 1 dams were treated with
      either saline or MO subcutaneously once a day (5 mg/kg on the first 2 days, 10
      mg/kg subsequently). Spontaneous locomotor activity in a new environment
      (habituation) and antinociceptive effects of MO were measured separately in male
      and female pups after weaning and also in late adolescence or adulthood. The
      rewarding effect of MO was assessed by conditioned place preference in adult
      animals. Both exposure-induced and sex differences were observed. A significant
      delay in habituation to a new environment and decreased sensitivity to the
      antinociceptive effect of MO were found in male offspring of MO-treated dams. In
      contrast, the place preference induced by MO was enhanced in the MO-exposed adult
      animals and this effect was more marked in females. Prenatal exposure to MO
      resulted in more marked changes than the postnatal exposure through maternal
      milk. The results indicate that a medium MO dose administered once-daily results
      in long-term consequences in offspring and may make them more vulnerable to MO
      abuse in adulthood.

PMID- 20038836
TI  - Reproducibility of the ambulatory arterial stiffness index in patients with type
      1 diabetes mellitus.
AB  - OBJECTIVES: The ambulatory arterial stiffness index (AASI) has been proposed as a
      novel indirect measure of arterial stiffness. We compared the repeatability of
      AASI and pulse pressure (PP), another marker of arterial stiffness, both computed
      from repeat 24-h ambulatory blood pressure recordings in patients with type 1
      diabetes mellitus. METHODS: Twenty-eight patients with type 1 diabetes mellitus
      and no previous or present treatment with antihypertensive drugs were recruited
      from outpatient clinics in Aarhus County and underwent two 24-h ambulatory blood
      pressure measurements, performed within 2 weeks in all participants except one.
      The repeatability of AASI and PP was assessed by (i) the Intraclass Correlation
      Coefficient (ICC) and (ii) the percentage of maximal variation, i.e. two times SD
      of the difference in the percentage of four times the SD of the mean of the
      paired measurements. RESULTS: The repeatability of AASI was considerably lower
      than for PP as estimated by ICC (0.38 vs. 0.90). The difference between ICCPP and
      ICCAASI was 0.51 confidence interval (0.25-0.82). Similarly, percentage of
      maximal variation was 68 and 23% respectively. CONCLUSION: AASI has a low
      repeatability compared with PP in type 1 diabetic patients. This questions the
      potential implementation of AASI in the daily clinic as a measure of arterial
      stiffness. Further studies are necessary to clarify this.

PMID- 20038837
TI  - Amniotic bands in paternal half-siblings.
AB  - We present two paternal half-siblings with constriction rings and limb reduction
      deformities, which seem to have been caused by amniotic bands. Their father has
      no evidence of amniotic bands nor any other congenital malformations and there is
      no wider family history of such malformations. There are few other reports of
      familial amniotic bands and these are either in mother-child pairs, siblings or
      in distant relatives. This is the first report of recurrence in paternal half
      siblings. Although no exact cause can be identified, this suggests that some
      genetic fetal factor, or factors, must be responsible for the amniotic bands in
      these cases.

PMID- 20038838
TI  - Ultrasound-guided epidural blood patch.

PMID- 20038839
TI  - Sudden death in sports among young adults in Norway.
AB  - AIM: The aim of the study was to explore sudden cardiac death during physical
      activity in young adults in Norway. MATERIALS AND METHODS: This retrospective
      study examined adults aged 15-34 years during the period 1990-1997. The Cause of
      Death Registry was used to identify cases of sudden cardiac death in sports.
      These cases were validated with information from medical records and autopsy
      reports. RESULTS: Twenty-three sports-related sudden deaths (22 men), mean age 27
      years (17-34 years), were identified. Causes of death were myocardial infarction
      (11), myocarditis (5), conduction abnormalities (2), aortic stenosis (1), cardiac
      rupture (1), hypertrophic obstructive cardiomyopathy (1), congenital coronary
      anomaly (1), and coronary sclerosis without defined infarction (1). The deaths
      were distributed across different types of sports activities. The incidence of
      deaths among physically active young men was 0.9 per 100,000. CONCLUSION: The
      number of myocardial infarctions is higher than expected. The incidence is
      similar to that found in other studies. A vast majority of the cases of death
      were men.

PMID- 20038841
TI  - Major life events increase the risk of stroke but not of myocardial infarction:
      results from the Copenhagen City Heart Study.
AB  - BACKGROUND: More attention has been paid to psychosocial conditions as possible
      risk factors for cardiovascular disease (CVD) and the impact of accumulated major
      life events (MLE) on the development of CVD has received little attention.
      DESIGN: The aim of this study was to explore the influences of MLE on CVD risk in
      a large cohort study. METHODS: The study population consisted of 9542 randomly
      selected adults free of CVD examined in the Copenhagen City Heart Study in 1991
      1994 and followed up for CVD defined as myocardial infarction or ischaemic stroke
      until 2001. MLE were analysed using an 11-item questionnaire and hazard ratios
      (HR) were calculated using the Cox proportional hazards model. RESULTS: During
      follow-up there were 443 myocardial infarctions (MI) and 350 ischaemic strokes.
      Financial problems in both childhood and adulthood were associated with risk of
      stroke with an HR of 1.71 (95% CI: 1.29-2.26) and 1.60 (1.12-2.30), respectively.
      Accumulation of MLE was also associated with risk of stroke with HR reaching a
      maximum of 1.41 (95% CI: 1.06-1.90) for more than one event in childhood and 1.49
      (95% CI: 1.09-2.04) for more than one event in adulthood. MLE accumulated over a
      life course showed a dose-response relationship with stroke. Associations were
      somewhat attenuated by adjustment for vital exhaustion suggesting a mediating
      role, but not by adjustment for behavioural risk factors. There were no
      associations between MLE and MI. CONCLUSION: In this population-based cohort
      study, we found that MLE conveyed a moderately increased risk of stroke partly
      mediated through vital exhaustion. We found no association between MLE and the
      risk of MI.

PMID- 20038840
TI  - Does baseline carotid intima-media thickness modify the effect of rosuvastatin
      when compared with placebo on carotid intima-media thickness progression? The
      METEOR study.
AB  - BACKGROUND: Many studies have used carotid intima-media thickness (CIMT)
      measurement to study atherosclerosis and the efficacy of interventions. The
      placebo-controlled Measuring Effects on intima-media Thickness: an Evaluation Of
      Rosuvastatin (METEOR) study showed significant reduction in the progression rate
      of maximum CIMT with 2 years of lipid treatment in asymptomatic individuals with
      subclinical atherosclerosis. DESIGN: The present post-hoc subgroup analysis of
      METEOR was carried out to determine whether the effect of rosuvastatin treatment
      varied according to baseline CIMT level. METHODS: To assess the relationship
      between efficacy of treatment with rosuvastatin versus placebo and baseline CIMT,
      we analyzed the effects on the primary CIMT endpoint in participants stratified
      by baseline quartiles of CIMT (Q1-Q4) using all individuals with a baseline
      reading and at least one post-baseline CIMT reading. Statistical analysis was
      carried out using a multilevel repeated-measures linear mixed effects model.
      RESULTS: In total, 876 participants were included in the analysis. In all
      quartiles, progression of mean maximum CIMT was significantly slower in
      rosuvastatin-treated individuals as compared with placebo controls. Although the
      magnitude of the treatment effect appeared larger in those with the highest
      baseline CIMT, statistical testing indicated that the magnitude of the treatment
      effect did not vary significantly with levels of baseline CIMT. CONCLUSION: This
      subgroup analysis of the METEOR study showed that in middle-aged adults with sub
      clinical atherosclerosis, rosuvastatin treatment resulted in significant
      reduction in mean maximum CIMT progression in four quartiles of baseline CIMT,
      with no evidence for difference in benefit across levels of baseline CIMT.

PMID- 20038842
TI  - The impact of frequent attenders on a UK emergency department.
AB  - BACKGROUND: Previous studies have identified that there is a cohort of frequent
      attenders to the emergency department (ED). Recent initiatives aim to provide
      care closer to home and alternatives to ED attendance. This study aims to
      identify what impact frequent attenders still have on the ED. METHODS: A chart
      review of frequent attenders to the ED was carried out over a 12-month period.
      Inclusion criterion was 10 or more attendances. Information collected comprised
      age, sex, postcode, next of kin, number of attendances, day of the week, time,
      referral source, mode of arrival, triage category, disposal, association with
      alcohol and drug use, presenting complaint, and diagnosis. RESULTS: Forty-four
      frequent users met the study criterion accounting for 1.9% of departmental
      activity. Sixty-four percent of frequent attenders were male with an average age
      of 49 years (range 19-83). The majority lived within 5 miles of the ED. Sixty
      percent of attendances arrived at the ED through ambulance. Documentation of
      either concurrent alcohol use or history of alcohol dependence and illicit drug
      use was reported in 54.6 and 15.9% of patients. The admission rate of this group
      was 38.5% higher than the total ED admission rate of 22%. CONCLUSION: There
      remains a cohort of frequent attenders that use the ED for their healthcare
      needs. A significant proportion of these attendances are associated with alcohol
      use, chronic disease or mental health problems. Reduction of attendances may be
      achieved by case management strategies and improving access to primary care and
      drug and alcohol services.

PMID- 20038843
TI  - The effects of temperature, age and sex on presentations of renal colic in
      Melbourne, Australia.
AB  - OBJECTIVE: To determine whether renal colic incidence in the temperate
      environment of Melbourne, Australia, varies with ambient temperature and season.
      METHODS: This was a retrospective analysis of patients with renal colic who
      presented, between 1999 and 2005 inclusive, to a Victorian inner city emergency
      department. The emergency department database was interrogated to identify
      patients with an International Classification of Diseases 10th revision
      diagnostic code of renal colic. All weather data were obtained from the Bureau of
      Meteorology (Melbourne, Australia). The primary study endpoints were renal colic
      incidence and mean monthly temperature and humidity. Data were analysed using
      Spearman's correlation coefficient and the normal Z-test. RESULTS: About 3070
      cases were identified. Mean age was 45.0 (SD 14.0) years. Males predominated with
      2374 (77.3%) cases. For both sexes, renal colic incidence was lower amongst
      younger and older patients. The summer rate was significantly greater than the
      winter rate (1.53 vs. 1.24 presentations/day, rate difference 0.29, 95%
      confidence interval 0.15-0.43, P<0.001). There were significant positive
      correlations between the mean monthly maximum temperature and the absolute number
      (R = 0.34, P = 0.002) and rate (presentations/day, R = 0.26, P = 0.017) of
      presentations. The summer/winter ratio of renal colic incidence was not affected
      by age or sex. CONCLUSION: The incidence of renal colic in the temperate
      environment increases with sustained increases in ambient temperature and is
      unaffected by age or sex. Patients at risk of renal colic should increase their
      fluid intake over the whole of the summer period not just during periods of
      extreme heat.

PMID- 20038844
TI  - Different characteristics of patients with gastro-oesophageal reflux disease on
      their path through healthcare: a population follow-up study.
AB  - BACKGROUND: Only a minority of patients with gastro-oesophageal reflux symptoms
      (GORS) seek medical advice. Little is known about patient characteristics
      associated with consultation in primary care and referral to secondary care. AIMS
      AND METHODS: We compared the characteristics of patients with GORS in the general
      population, those who consulted their general practitioner (GP) and those
      referred to secondary care for upper endoscopy. We aimed to identify differences
      between patients with short term (<90 days) and chronic symptoms, and differences
      between patients with symptoms in primary and secondary care. The study was
      performed in a primary care based prospective dynamic population. RESULTS: In
      total, 16% of 7237 adult patients were identified with GORS. Twenty-five percent
      of these patients consulted the GP, of whom 40% were referred for endoscopy.
      Patients with chronic GORS were older, had a higher body mass index, were more
      often referred for upper endoscopy (all P<0.001) and more frequently had relevant
      findings during endoscopy (oesophagitis: 50% and Barrett's oesophagus: 10%).
      Patients referred for upper endoscopy were older than nonreferred patients
      (P<0.001). CONCLUSION: Only a minority of people with GORS visit their GP. After
      consulting referral for endoscopy occurs relatively often. Underlying endoscopic
      abnormalities are frequently found in patients with chronic GORS.

PMID- 20038845
TI  - Children's Digestive Health and Nutrition Foundation: building on the past, a
      foundation for the future.

PMID- 20038846
TI  - Chronic hepatitis C virus infection in children.
AB  - The importance of hepatitis C viral infection in the health care of children has
      grown in recent decades. More is now known about the epidemiology of this
      infection in children and the progression of disease in the pediatric age group,
      and the treatment options are increasing. In this review, we update readers on
      the state of our understanding of hepatitis C infection in children, provide the
      current recommendations for monitoring and treatment, and discuss emerging
      therapies.

PMID- 20038847
TI  - A 7-month-old boy with liver abscesses.

PMID- 20038848
TI  - Characterization of ATP8B1 gene mutations and a hot-linked mutation found in
      Chinese children with progressive intrahepatic cholestasis and low GGT.
AB  - OBJECTIVES: The aim of the study was to elucidate the role and characteristics of
      ATP8B1 gene mutations in mainland Chinese children with progressive intrahepatic
      cholestasis and low gamma-glutamyltransferase (GGT). PATIENTS AND METHODS: Twenty
      four children who presented with progressive intrahepatic cholestasis and low GGT
      were admitted to a tertiary pediatric hospital in eastern China from January 2004
      to July 2007. Five children with homozygous or compound heterozygous ABCB11 gene
      mutations were excluded from the study. All encoding exons and their flanking
      areas of ATP8B1 gene were sequenced in the remaining 19 patients, in whom only 1
      or no mutation of ABCB11 was found. Clinical features and liver histology
      obtained by reviewing the medical records were compared among patients with
      different genotypes. RESULTS: Nine mutations of ATP8B1 gene were found in 9
      patients. All of them were novel except for mutations I694N and R952X. A linked
      P209T and IVS6+5G>T mutation was found in 4 of 9 patients, including 2
      homozygotes and 2 heterozygotes. Giant cell transformation of hepatocytes was
      demonstrated in 1 of 6 patients with ATP8B1 mutations and 4 of 5 patients with
      ABCB11 mutations. CONCLUSIONS: ATP8B1 gene mutations play an important role in
      Chinese patients with progressive intrahepatic cholestasis and low GGT. The
      linked mutation P209T and IVS6+5G>T is a hot mutation in the Chinese population.
      Histological examination may be helpful in differentiating familial intrahepatic
      cholestasis type 1 from bile salt export pump-related disease.

PMID- 20038849
TI  - Parenteral fish oil as monotherapy prevents essential fatty acid deficiency in
      parenteral nutrition-dependent patients.
AB  - OBJECTIVE: The use of fish oil-based emulsions as the sole source of fat for
      patients receiving parenteral nutrition (PN) has raised concerns for the
      development of essential fatty acid deficiency (EFAD), hindering its adoption
      into clinical practice. The purpose of the present study was to examine fatty
      acid profiles of patients receiving no enteral energy, while completely dependent
      on PN and an intravenous fish oil-based lipid emulsion, for onset of EFAD and
      maintenance of growth. PATIENTS AND METHODS: Prospectively collected data from 10
      patients were reviewed for evidence of EFAD, defined as a triene:tetraene ratio
      >0.2. Gestational age-adjusted z scores for length, growth, and head
      circumference at baseline were compared with the corresponding z scores at time
      of censoring. All of the patients received PN with a fish oil-based lipid
      emulsion at 1 g . kg . day as the sole source of fat energy for at least 1 month.
      The fish oil monotherapy was used under a compassionate use protocol. RESULTS:
      Median gestational age at the time of birth was 35 weeks, and median age at the
      start of treatment was 3.5 months. After a median time of 3.8 months on exclusive
      PN and fish oil-based lipid emulsion, none of the patients developed biochemical
      or clinical evidence of EFAD. z scores were not statistically different,
      indicating no growth impairment. Median direct bilirubin levels improved in 9
      patients from 6.8 to 0.9 mg/dL (P = 0.009). CONCLUSIONS: : When dosed
      appropriately, fish oil-based lipid emulsions contain sufficient amounts of
      essential fatty acids to prevent EFAD and sustain growth in patients who are
      completely dependent on PN.

PMID- 20038850
TI  - In situ expression of cagA and risk of gastroduodenal disease in Helicobacter
      pylori-infected children.
AB  - BACKGROUND AND AIM: Gastroduodenal disease is more common among adults and
      children with cagA+ Helicobacter pylori infection, but disease severity varies
      among those infected with cagA+ strains. We examined whether cagA in situ
      expression can predict disease manifestations among H pylori-infected children.
      PATIENTS AND METHODS: Fifty-one children were selected from 805 patients with
      abdominal symptoms who underwent esophagogastroduodenoscopy with gastric
      biopsies. Endoscopic and histologic gastritis were scored and H pylori
      colonization was quantified by Genta stain and in situ hybridization expression
      of 16S rRNA and cagA. RESULTS: Endoscopy was either normal (n = 14) or
      demonstrated nodularity (n = 18), gastric ulcer (n = 8) or duodenal ulcer (n =
      11). H pylori was present in 7, 18, 6, and 10 children, respectively. Expression
      of 16S rRNA and cagA were significantly higher in children with ulcer compared
      with normal children. The fraction of H pylori bacteria expressing cagA in situ
      was higher in children with ulcer compared to those with endoscopic nodularity (P
      < 0.05). CONCLUSIONS: Thus, cagA in situ expression is increased in H pylori
      infected children with peptic ulcers and may play a role in the pathogenesis of
      peptic ulcer disease during childhood. Determination of in situ expression of
      cagA complements traditional isolation and in vitro testing of single-colony
      isolates.

PMID- 20038851
TI  - Aluminum content of parenteral nutrition in neonates: measured versus calculated
      levels.
AB  - BACKGROUND AND OBJECTIVE: Aluminum (Al) is associated with significant central
      nervous system toxicity and bone and liver damage. Because Al is a contaminant of
      parenteral nutrition (PN) components including calcium and phosphate additives,
      premature infants are at potentially high risk for toxicity. The US Food and Drug
      Administration (FDA) has mandated PN component product labeling and recommended
      maximum Al daily exposure limits. The objective of this article is to determine
      the actual Al content of neonatal PN solutions, compare these values to the
      calculated amounts from manufacturers' PN product labels, and ascertain whether
      the actual Al exposure exceeds the FDA recommended maximum of 5 microg . kg(-1) .
      day(-1). MATERIALS AND METHODS: Samples from 40 neonatal patient PN solutions
      were selected for sampling and Al content determination. Samples were also taken
      from 16 manufacturer's component products used in PN formulation. All of the
      samples were sent to Mayo Laboratories for Al content measurement. The calculated
      Al concentrations in PN samples were determined from the manufacturer's labeled
      content. RESULTS: Both measured and calculated Al concentrations exceeded the FDA
      recommended safe limit of <5 microg . kg(-1) . day(-1). The actual measured Al
      content was significantly lower than the calculated Al content in both the
      patient PN solutions and the component product samples. CONCLUSIONS: Al exposure
      exceeded the FDA recommended maximum limit for all patient samples; however, the
      actual measured Al content of all the samples was significantly less than the
      calculated Al content based on manufacturer's labels. These findings suggest that
      manufacturers label their products with actual Al content at the time of product
      release rather than at time of expiration. Periodic monitoring of Al levels
      should be considered with prolonged PN therapy. Changes in manufacturing
      processes, including the use of better raw materials, are essential to reduce Al
      contamination to meet FDA mandates.

PMID- 20038852
TI  - Effects of vitamin A supplementation on intestinal barrier function, growth,
      total parasitic, and specific Giardia spp infections in Brazilian children: a
      prospective randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: This study evaluates the effects of retinol on intestinal barrier
      function, growth, total parasites, and Giardia spp infections in children in
      northeastern Brazil. SUBJECTS AND METHODS: The study was a double-blind,
      randomized placebo-controlled trial (http://clinicaltrials.gov; register no.
      #NCT00133406) involving 79 children who received vitamin A 100,000-200,000 IU (n
      = 39) or placebo (n = 40) at enrollment, 4, and 8 months and were followed for 36
      months. Intestinal barrier function was evaluated using the lactulose:mannitol
      ratio test. Stool lactoferrin was used as a marker for intestinal inflammation.
      RESULTS: The groups were similar with regard to age, sex, nutritional parameters
      (z scores), serum retinol concentrations, proportion of lactoferrin-positive
      stool samples, and intestinal barrier function. The lactulose:mannitol ratio did
      not change during the same time of follow-up (P > 0.05). The proportion of
      lactoferrin-positive samples evaluated at 1 month did not change between groups
      (P > 0.05). Total intestinal parasitic, specifically new, infections were
      significantly lower in the vitamin A treatment compared with control group; these
      were accounted for entirely by significantly fewer new Giardia infections in the
      vitamin A treatment group. The cumulative z scores for weight-for-length or
      height, length or height-for-age z scores, and weight-for-age did not change
      significantly with vitamin A intervention for 36 months of follow-up.
      CONCLUSIONS: These data showed that total parasitic infection and Giardia spp
      infections were significantly lower in the vitamin A treatment group when
      compared with the placebo group, suggesting that vitamin A improves the host's
      defenses against Giardia infections.

PMID- 20038853
TI  - Whole-blood-free choline and choline metabolites in infants who require chronic
      parenteral nutrition therapy.
AB  - BACKGROUND AND AIM: Choline deficiency is associated with hepatic dysfunction.
      Parenteral nutrition (PN) and lipid emulsions contain phosphatidylcholine
      (PtdCho) but insignificant free choline (FCho). PtdCho is sequentially degraded
      to glycerolphosphocholine (GPCho), phosphocholine (PCho), and finally to FCho.
      Biosynthesis of FCho may be insufficient during PN therapy. The aim of the study
      was to examine the status of FCho and related metabolites in infants on prolonged
      (> or =4 weeks) PN. METHODS: Whole blood concentrations of FCho, PtdCho, GPCho,
      and PCho were measured and compared in infants on PN and infants on enteral feeds
      (controls). RESULTS: Infants on PN (n = 14) had higher birth weight but same
      postnatal age as controls (n = 14) (mean +/- standard deviation) 8.3 +/- 3.9
      versus 7.4 +/- 3.6 weeks. Parenteral nutrition was associated with increased
      PtdCho 1761 +/- 452 versus 1471 +/- 221 nmol/mL, P = 0.04. Mean whole blood FCho,
      GPCho, and PCho concentrations did not differ significantly in PN versus
      controls: 40.0 +/- 15.4 versus 50.8 +/- 49.7, 16.4 +/- 14.5 versus 25.2 +/- 29.3,
      and 15.3 +/- 13.5 versus 22.0 +/- 14.8 nmol/mL, respectively. However, PCho was
      positively correlated with GPCho in controls (r = 0.91, P < 0.01) but not PN (r =
      0.24, P = NS), and infants receiving >90% of daily energy intake from PN (n = 6)
      had decreased PCho, 5.7 +/- 4.1 nmol/mL, compared with those receiving <90% of
      daily energy intake (n = 8) 22.5 +/- 13.7 nmol/mL, P < 0.05, and controls, 22.0
      +/- 14.8 nmol/mL, P < 0.01. CONCLUSIONS: Decreased whole-blood concentrations of
      choline suggest possible evidence of choline deficiency as illustrated by
      decreased whole-blood PCho. Choline supplementation should be investigated in
      infants who require prolonged PN, and whole-blood PCho can be used to monitor
      response.

PMID- 20038854
TI  - Preliminary report: resection and interposition of a deepithelialized skin flap
      graft in tarsal coalition in children.
AB  - Six tarsal coalitions in children were managed surgically using a
      deepithelialized skin flap for interposition after resection of the bony, fibrous
      or cartilaginous coalition. The advantage of this technique is that due to
      positioning the skin flap, joint motion can be preserved. The clinical results
      using the Ankle Hindfoot Scale of the American Orthopedic Foot and Ankle Society
      were excellent in two and good in four cases. The radiographs at follow-up showed
      no recurrences of the resected coalitions. This study shows that the use of
      deepithelialized skin flap interposition is effective in providing pain relief
      for the patients in symptomatic coalitions.

PMID- 20038855
TI  - Automated measurement of "pressure times time dose" of intracranial hypertension
      best predicts outcome after severe traumatic brain injury.
AB  - BACKGROUND: Earlier, more accurate assessment of secondary brain injury is
      essential in management of patients with traumatic brain injury (TBI). We
      assessed the accuracy and utility of high-resolution automated intracranial
      pressure (ICP) and cerebral perfusion pressure (CPP) recording and their analysis
      in patients with severe TBI. METHODS: ICP and CPP data for 30 severe TBI patients
      were collected automatically at 6-second intervals. The degree and duration of
      ICP and CPP above and below treatment thresholds were calculated as "pressure
      times time dose" (PTD; mm Hg . h) using automated recordings (PTDa) or manual
      recordings (PTDm) for early stage (trauma resuscitation unit [TRU]) and total
      monitoring time (TRU and intensive care unit). RESULTS: Bland-Altman plots showed
      lack of agreement between PTDa and PTDm. For ICP >20 mm Hg and CPP <60 mm Hg,
      PTDa, but not PTDm, was significantly higher in patients with unfavorable outcome
      (Extended Glasgow Outcome Scale score <or=4) than in patients with favorable
      outcome (Extended Glasgow Outcome Scale score >4). Total PTDa for ICP >20 mm Hg
      and CPP <60 mm Hg had high predictive power for functional outcome (area under
      the receiver operating characteristics curve: 0.92 +/- 0.05 and 0.82 +/- 0.08,
      respectively) and inhospital mortality (0.76 +/- 0.15 and 0.79 +/- 0.14,
      respectively) and were strongly correlated with length of intensive care unit
      stay (p = 0.009 and 0.007), length of hospital stay (p = 0.009 and 0.005), and
      discharge Glasgow Coma Scale scores (p = 0.008 and p = 0.038). PTDa of CPP >100
      mm Hg during TRU monitoring and during the first 24 hours showed highest
      predictive power for mortality (area under the receiver operating characteristics
      curve: 0.72 +/- 0.18 and 0.85 +/- 0.13, respectively). PTDa was better than PTDm
      and the duration of episodes alone in predicting outcome. CONCLUSIONS: PTD
      calculation of high resolution ICP and CPP recording is a reliable and feasible
      way of monitoring severe TBI patients.

PMID- 20038856
TI  - Simplified estimates of the probability of death after burn injuries: extending
      and updating the baux score.
AB  - BACKGROUND: : Generations of clinicians have used the Baux score, defined as the
      sum of age in years and percent body burn, to predict percent mortality after
      trauma, but advances in burn care have rendered the predictions of this score too
      pessimistic. Additionally, this score does not include the effects of inhalation
      injury. METHODS: : We revised the Baux score to include inhalation injury and
      recalibrated its predictions using a single-term logistic regression model
      developed using data on 39,888 burned patients provided by the national burn
      repository. We compared this revised Baux score to a more complex logistic
      regression model derived from the same data set and predictors. RESULTS: : A
      preliminary logistic regression model showed that age and percent burn contribute
      almost equally to mortality and further that the presence of inhalation injury
      added the equivalent of 17 years (or 17% burn). These observations suggested a
      revised Baux Score:Age + Percent Burn + 17 * (Inhalation Injury, 1 = yes, 0 =
      no)A logistic model based on the Revised Baux Score performed well, but a more
      complex model obtained using modern statistical model building tools had better
      discrimination and calibration. CONCLUSIONS: : Our proposed revised Baux score is
      simple enough for mental calculation, and its inverse logit transformation
      (provided with a calculator or nomogram) can provide precise predictions of
      mortality. Better predictions can be obtained using our more complex statistical
      model. Burn surgeons and nurses accustomed to using the original Baux score may
      welcome an updated version.

PMID- 20038858
TI  - Clinical and imaging correlations of bone turnover markers in prostate cancer
      patients with bone only metastases.
AB  - OBJECTIVES: To correlate serum levels of bone markers with pain levels and extent
      of skeletal disease (EOD), in patients suffering from prostate cancer with bone
      only metastases. METHODS: Thirty-six males with hormone-refractory prostate
      carcinoma, bone only metastases and no history of therapies, drugs, or diseases
      that affect bone metabolism were studied. Karnofsky performance status, pain
      scoring, EOD, osteocalcin (OC), prostate-specific antigen, bone alkaline
      phosphatase amino-terminal and carboxy-terminal propeptides and telopeptides of
      type I collagen were analysed. Twenty-four healthy controls of the same age were
      also established. RESULTS: With only the exception of OC, bone marker values of
      patients were significantly increased compared with the upper reference limits
      (P<0.0001 for bone alkaline phosphatase and amino-terminal telopeptide of type I
      collagen, 0.012 for amino-terminal propeptide of type I collagen, 0.0023 for
      carboxy-terminal propeptide of type I collagen, and 0.04 for carboxy-terminal
      telopeptide of type I collagen). All bone markers and prostate-specific antigen
      also showed significant paired correlations (P < or = 0.019) and linear increases
      with advancing EOD (P < or = 0.032). Finally, none of the measured markers
      correlated significantly with pain levels. CONCLUSION: Bone markers are
      remarkably elevated in the serum of prostate cancer patients with metastatic bone
      disease and correlate with EOD. Paired correlations also suggest an accelerated
      but proportional (coupled) bone metabolism.

PMID- 20038857
TI  - Acute lung injury in patients with traumatic injuries: utility of a panel of
      biomarkers for diagnosis and pathogenesis.
AB  - BACKGROUND: The diagnosis of acute lung injury (ALI) is based on a consensus
      clinical definition. Despite the simplicity of this definition, ALI remains
      underdiagnosed and undertreated. Severe trauma is a well-described cause of ALI
      that represents a relatively homogeneous subset of patients with ALI. The aims of
      this study were to develop a panel of plasma biomarkers to facilitate diagnosis
      of trauma-induced ALI and to enhance our understanding of the pathogenesis of
      human ALI. METHODS: A retrospective nested case control of 192 patients admitted
      to the trauma intensive care unit at a university hospital between 2002 and 2006.
      We compared 107 patients with ALI to 85 patients without ALI. Plasma was
      collected within 72 hours of intensive care unit admission. Twenty-one plasma
      biomarkers were measured in duplicate in each plasma sample. RESULTS: Patients
      with ALI had higher severity of illness scores, more days of mechanical
      ventilation, longer hospital stays, and higher mortality versus controls. Seven
      biomarkers (receptor for advanced glycation end products, procollagen peptide
      III, brain natriuretic peptide, angiopoietin-2, interleukin-10, tumor necrosis
      factor alpha, and interleukin-8) had a high diagnostic accuracy as reflected by
      the area under the receiver operating characteristic curve of 0.86 (95%
      confidence interval, 0.82-0.92) in differentiating ALI from controls.
      CONCLUSIONS: A model using seven plasma biomarkers had a high diagnostic accuracy
      in differentiating patients with trauma-induced ALI from trauma patients without
      ALI. In addition, use of a panel of biomarkers provides insight into the likely
      importance of alveolar epithelial injury in the pathogenesis of early ALI.

PMID- 20038859
TI  - Genetic variability in the ACE gene region surrounding the Alu I/D polymorphism
      is maintained by balancing selection in human populations.
AB  - OBJECTIVE: Angiotensin-converting enzyme plays a critical role in the maintenance
      of cardiovascular homeostasis. Extensive research has aimed at identifying ACE
      genetic variants responsible for variation in enzyme plasma concentrations and
      associated with human diseases. These efforts have been hampered by the extensive
      linkage disequilibrium across the gene and the identity or location of the
      functional polymorphism(s) is at presently unknown. The aim of our study was to
      verify whether the Alu insertion/deletion (Alu I/D) polymorphism or any linked
      variant has been maintained by natural selection in human populations. METHODS:
      We resequenced a gene region surrounding the Alu I/D polymorphism in four human
      populations; we applied population neutrality tests and performed haplotype
      analysis for this region. RESULTS: We observed high levels of nucleotide
      diversity, an excess of intermediate frequency alleles and, at least in African
      populations, a higher level of within-species diversity compared with
      interspecific divergence. Analysis of haplotype genealogy indicated the presence
      of two major clades separated by deep branches with a coalescence time older than
      1.5 million years. All these features strongly suggest the action of balancing
      selection and we verified that the selection signature is restricted to the gene
      region surrounding the Alu I/D. CONCLUSION: Our data imply the presence of a
      functional polymorphism in the Alu I/D region and illustrate the contribution of
      evolutionary models to classic single nucleotide polymorphism-phenotype
      association approaches by providing information about the localization of
      candidate functional variants.

PMID- 20038860
TI  - Macular functional changes evaluated with MP-1 microperimetry after intravitreal
      bevacizumab for subfoveal myopic choroidal neovascularization: one-year results.
AB  - PURPOSE: The purpose of this study was to evaluate 1-year functional and
      structural effects of intravitreal bevacizumab for subfoveal choroidal
      neovascularization secondary to pathologic myopia (myopic choroidal
      neovascularization). METHODS: Fifteen eyes with myopic choroidal
      neovascularization participated in this prospective interventional,
      noncomparative case series. All patients were treated with one intravitreal
      injection of 1.25 mg bevacizumab. Retreatments were performed in case of
      persistent or recurrent leakage on fluorescein angiography and/or intraretinal
      fluid on optical coherence tomography. Evaluation of best-corrected visual acuity
      using Early Treatment of Diabetic Retinopathy Study criteria, MP-1
      microperimetry, optical coherence tomography, and fluorescein angiography were
      performed before treatment and 1 month, 3 months, 6 months, and 1 year after
      treatment. RESULTS: After a follow-up of 12 months, best-corrected visual acuity
      improved on average of 0.23 logarithm of the minimum angle of resolution. Mean
      macular sensitivity within the central 8 degrees increased on average of 2.62 dB
      at 12-month postinjection. The mean number of measurement points within the
      central absolute scotoma reduced significantly from 12.47 before treatment to
      6.27 at 1-year follow-up. An improvement of fixation stability from baseline was
      observed in 9 patients (60%). No treatment adverse events were evidenced.
      CONCLUSION: Improvement of macular sensitivity and fixation stability 1 year
      after intravitreal bevacizumab for myopic choroidal neovascularization suggest a
      stable and progressive macular function recovery. The mean treatment session was
      1.53, with 53.3% of patients needing only a single intravitreal bevacizumab
      injection, supporting a potential long-lasting efficacy of intravitreal
      bevacizumab treatment.

PMID- 20038861
TI  - Disruption of the photoreceptor inner segment/outer segment layer on spectral
      domain-optical coherence tomography is a predictor of poor visual acuity in
      patients with epiretinal membranes.
AB  - PURPOSE: The purpose of this study was to evaluate the predictive value of
      spectral domain-optical coherence tomography-determined integrity of the
      photoreceptor inner segment/outer segment (IS/OS) junction on visual acuity in
      patients with epiretinal membranes (ERMs). METHODS: This is a retrospective
      consecutive case series of 54 eyes from 48 patients with primary ERMs who
      underwent spectral domain-optical coherence tomography scans. Regression analysis
      was used to calculate the relative contribution of several variables, including
      photoreceptor IS/OS disruption, grade of IS/OS disruption, macular thickness, and
      ERM grade on fundus imaging to visual acuity. RESULTS: The strongest individual
      predictor of visual acuity among patients with ERM was central retinal thickness
      on spectral domain-optical coherence tomography (r(2) = 0.16, P = 0.0024), but
      the most efficient model was the combination of macular thickness and presence or
      absence of photoreceptor IS/OS disruption (r(2) = 0.24, P = 0.0008). Additional
      measured variables did not significantly contribute to visual acuity prediction.
      Inner segment/outer segment layer integrity was also an independent predictor of
      visual acuity, and patients with IS/OS disruption were 6.88 times as likely to
      have 20/50 or worse vision than patients with intact photoreceptor layers (odds
      ratio: 6.88, confidence interval: 1.56-30.43, P = 0.01). CONCLUSION: Disruption
      of the photoreceptor IS/OS junction is a statistically significant predictor of
      poor visual acuity among patients with ERM and is most useful when combined with
      central retinal thickness measurement.

PMID- 20038862
TI  - Complement factor H polymorphism in age-related maculopathy in the Chinese
      population: the Beijing Eye Study.
AB  - PURPOSE: The purpose of this study was to analyze the association between the
      Y402H polymorphism in the complement factor H and soft drusen of the macula as
      part of age-related maculopathy in the Chinese population. METHODS: In the
      population-based Beijing Eye Study, the participants underwent a detailed
      ophthalmic examination including fundus photography. All fundus photographs were
      graded using the Wisconsin Grading System. Of 515 subjects with soft drusen in
      the macula, 208 (40.4%) subjects had blood samples taken and were thus eligible
      for the present study. These subjects were compared with 140 randomly selected
      control subjects from the Beijing Eye Study matched for age, sex, and rural
      versus urban area with the study group. The analysis of the genotype was
      performed by allele-specific digestion of polymerase chain reaction products.
      RESULTS: Dividing the study group into subjects with bilateral soft drusen and
      unilateral soft drusen showed a significant association between the Y402H
      polymorphism in the complement factor H gene and the study group with bilateral
      soft drusen with an odds ratio of 2.29 (95% confidence interval, 1.06-4.95).
      CONCLUSION: Also in the Chinese population, soft drusen as part of age-related
      maculopathy are associated with the Y402H polymorphism in the complement factor H
      gene despite a markedly lower frequency of C allele in the Chinese population
      than in white populations.

PMID- 20038863
TI  - Preliminary assessment of celecoxib and microdiode pulse laser treatment of
      diabetic macular edema.
AB  - PURPOSE: Inflammation may play an important role in the pathogenesis of diabetic
      macular edema, a major cause of vision loss in persons with diabetes. The purpose
      of this study was to evaluate combined antiinflammatory therapy and laser
      approaches for treating patients with diabetic macular edema. METHODS: In this
      prospective, factorial, randomized, multicenter trial, we compared cyclo
      oxygenase-2 inhibitor (celecoxib) with placebo and diode grid laser with standard
      Early Treatment Diabetic Retinopathy Study focal laser treatment in 86
      participants with diabetic macular edema. The primary outcome is change in visual
      acuity of > or = 15 letters from baseline, and the secondary outcomes include a
      50% reduction in the retinal thickening of diabetic macular edema measured by
      optical coherence tomography and a 50% reduction in leakage severity on
      fluorescein angiography. RESULTS: Visual acuity and retinal thickening data from
      >2 years of follow-up did not show evidence of differences between the medical
      and laser treatments. However, participants assigned to the celecoxib group were
      more likely to have a reduction in fluorescein leakage when compared with the
      placebo group (odds ratio = 3.6; P < 0.01). CONCLUSION: This short-term study did
      not find large visual function benefits of treatment with celecoxib or diode
      laser compared with those of standard laser treatment. A suggestive effect of
      celecoxib in reducing fluorescein leakage was observed.

PMID- 20038864
TI  - Intravitreal ranibizumab for choroidal neovascularization complicating pathologic
      myopia.
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of intravitreal
      injections of ranibizumab in choroidal neovascularization secondary to pathologic
      myopia. METHODS: A prospective case series of 32 eyes of 32 patients affected
      with choroidal neovascularization secondary to pathologic myopia treated by
      intravitreal injections of ranibizumab. Best-corrected visual acuity, fundus
      examination, fluorescein angiography, indocyanine green angiography, and spectral
      domain-optical coherence tomography were performed for the diagnosis of myopic
      choroidal neovascularization. Best-corrected visual acuity and central retinal
      thickness measurement were performed monthly during the follow-up. RESULTS: The
      median number of injections was 3 with a median follow-up of 17 months. The
      median visual acuity at baseline was 20/100 and improved to 20/50 at final
      examination (P < 0.0001). Best-corrected visual acuity improved by > or = 3 lines
      in 15 of 32 eyes (46.8%). The median central thickness was 336 microm (range, 179
      663 microm) at baseline and 233 microm (range, 125-465 microm) at final
      examination (P < 0.0001). No severe drug-related side effect was reported.
      CONCLUSION: In our series of myopic choroidal neovascularization, intravitreal
      injections of ranibizumab showed visual acuity improvement and retinal thickness
      reduction. Further prospective multicentric clinical trials are needed to
      evaluate the safety and the efficacy of this treatment.

PMID- 20038865
TI  - HIV trends in adolescents: tracing our steps in preparation for our future.

PMID- 20038866
TI  - Integration of HIV testing and linkage to care by the Baltimore City Health
      Department.

PMID- 20038867
TI  - Revision rates following primary adult spinal deformity surgery: six hundred
      forty-three consecutive patients followed-up to twenty-two years postoperative.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the prevalence of and
      reasons for unanticipated revision surgery in an adult spinal deformity
      population treated at one institution. SUMMARY OF BACKGROUND DATA: No recent
      studies exist that analyze the rate or reason for unanticipated revision surgery
      for adult spinal deformity patients over a long period. METHODS: All patients
      presenting for primary instrumented spinal fusion with a diagnosis of adult
      deformity at a single institution from 1985 to 2008 were reviewed using a
      prospectively acquired database. All surgical patients with instrumented fusion
      of > or =5 levels using hooks, hybrid, or screw-only constructs were identified.
      Patient charts and radiographs were reviewed to provide information as to the
      indication for initial and any subsequent reoperation. A total of 643 patients
      underwent primary instrumented fusion for a diagnosis of adult idiopathic
      scoliosis (n = 432), de novo degenerative scoliosis (n = 104), adult kyphotic
      disease (n = 63), or neuromuscular scoliosis (n = 45). The mean age was 37.9
      years (range, 18-84). Mean follow-up for the entire cohort was 4.7 years, and 8.2
      years for the subset of the cohort requiring reoperation (range, 1 month-22.3
      years). RESULTS: A total of 58 of 643 patients (9.0%) underwent at least one
      revision surgery and 15 of 643 (2.3%) had more than one revision (mean 1.3;
      range, 1-3). The mean time to the first revision was 4.0 years (range, 1 week
      19.7 years). The most common reasons for revision were pseudarthrosis (24/643 =
      3.7%; 24/58 = 41.4%), curve progression (13/643 = 2.0%; 13/58 = 20.7%), infection
      (9/643 = 1.4%; 9/58 = 15.5%), and painful/prominent implants (4/643 = 0.6%; 4/58
      = 6.9%). Uncommon reasons consisted of adjacent segment degeneration (3), implant
      failure (3), neurologic deficit (1), and coronal imbalance (1). Revision rates
      over the follow-up period were: 0 to 2 years (26/58 = 44.8%), 2 to 5 years (17/58
      = 29.3%), 5 to 10 years (7/58 = 12.1%), >10 years (8/58 = 13.8%). CONCLUSION:
      Repeat surgical intervention following definitive spinal instrumented fusion for
      primary adult deformity performed at a single institution demonstrated a
      relatively low rate of 9.0%. The most common reasons for revision were
      predictable and included pseudarthrosis, proximal or distal curve progression,
      and infection.

PMID- 20038868
TI  - Can posterior-only surgery provide similar radiographic and clinical results as
      combined anterior (thoracotomy/thoracoabdominal)/posterior approaches for adult
      scoliosis?
AB  - STUDY DESIGN: Retrospective matched cohort analysis. OBJECTIVE: To determine if
      posterior-only (post-only) surgical techniques consisting of pedicle screws,
      osteotomies, transforaminal lumbar interbody fusion, and bone morphogenetic
      protein-2 may provide similar results as compared anterior
      (thoracotomy/thoracoabdominal)/posterior surgical approaches for the treatment of
      adult spinal deformity with respect to correction, fusion rates, or outcomes.
      SUMMARY OF BACKGROUND DATA: Combined anterior/posterior (A/P) fusion has
      traditionally been used to treat many adult scoliosis deformities. Anterior
      approaches negatively impact pulmonary function and require additional operative
      time and anesthesia. METHODS: Twenty-four patients who had A/P fusion for primary
      adult scoliosis (16 staged, 8 same-day) were matched with a cohort of 24 patients
      who had post-only treatment. Anterior fusion was performed via a thoracotomy (n =
      1)/thoracoabdominal (n = 23) approach. All post-only surgeries were under one
      anesthesia. Minimum 2-year follow-up included radiographic, clinical, and
      outcomes data. RESULTS: There were no significant differences between groups for
      age, gender, diagnosis, comorbidities, preoperative curve magnitudes, or global
      balance. Postoperative radiographic correction and alignment were similar for
      both groups except for thoracolumbar curve percent improvement which was
      statistically better in the post-only group (P = 0.03). The average surgical time
      was higher in A/P versus post-only group (11.6 vs. 6.9 hours, P < 0.0001) as was
      total estimated blood loss (1330 vs. 980 mL, P = 0.04). Hospital length of stay
      (LOS) was longer in A/P versus post-only group (11.9 vs. 8.3 days, P = 0.03).
      There were no significant differences between postoperative complications.
      Revision surgery was performed in 5 A/P and 2 post-only patients. Higher
      pseudarthrosis rates found in the A/P versus post-only (17 vs. 0%) were not
      significant (P = 0.11). SRS-30 and Oswestry scores reflected a similar patient
      assessment before surgery, and improvement between groups at follow-up.
      CONCLUSION: Post-only adult scoliosis surgery achieved similar correction to A/P
      surgery while decreasing blood loss, operative time, length of stay, and avoiding
      additional anesthesia. Complications, radiographic, and clinical outcomes were
      similar at over 2-year follow-up.

PMID- 20038869
TI  - Health-related quality of life in untreated versus brace-treated patients with
      adolescent idiopathic scoliosis: a long-term follow-up.
AB  - STUDY DESIGN: The previous Scoliosis Research Society brace study (JBJS-A, 1995)
      included patients with adolescent idiopathic scoliosis (AIS) with moderate curve
      sizes (25 degrees -35 degrees). The Swedish patients in this study were examined
      in a long-term follow-up. OBJECTIVE: The aim was to analyze and compare quality
      of life in adulthood between AIS patients who were only observed or treated with
      a brace during adolescence. SUMMARY OF BACKGROUND DATA: Quality of life as
      measured by the SRS-22 has not previously been presented for adult untreated AIS
      patients. METHODS: Forty patients who were only observed (due to a curve increase
      of less than 6 degrees until maturity), and 37 brace-treated patients attended
      the complete follow-up, including clinical and radiologic examination, and
      answered 2 quality of life questionnaires (SRS-22 and Short Form-36 [SF-36]).
      RESULTS: No differences were found between the groups in terms of age at follow
      up (mean: 32 years), follow-up time after maturity (mean: 16.0 years), and curve
      size at inclusion (mean: 30 degrees) or at follow-up (mean: 35 degrees). The SRS
      22/total score was a mean of 4.2 for braced patients and 4.1 for only observed
      patients. Neither total scores/subscales of the SRS-22 or SF-36 differed
      significantly between the groups. For the SF-36, no differences in relation to
      the Swedish age-matched norm scales were found for either group. CONCLUSION:
      Patients with moderate AIS report good quality of life in their 30s, as measured
      by both the SRS-22 and SF-36, regardless of whether they received no active
      treatment or were brace treated during adolescence. Neither of the groups
      displayed any difference compared with the age-matched norm groups for the SF-36.

PMID- 20038870
TI  - Scoliosis Research Society: 2005 and beyond.

PMID- 20038871
TI  - Bridge the nursing generation gap.

PMID- 20038872
TI  - Healthcare reform--get in the game!

PMID- 20038873
TI  - Standard 60: catheter clearance.

PMID- 20038874
TI  - Preparation of the pediatric patient for invasive procedures.
AB  - It is well documented in pediatric literature that intrusive healthcare
      experiences can have a profound negative impact on a child's psychological well
      being for months to years after the experience. The purpose of this article is to
      share some general techniques and strategies for fostering patient coping. By
      utilization of techniques for preparation, procedural support, and follow-up,
      healthcare providers can minimize adverse effects of the patient's experiences in
      healthcare settings.

PMID- 20038875
TI  - The use of smart pumps for preventing medication errors.
AB  - The use of smart pumps can be helpful for preventing medication errors,
      especially with high-alert drugs in vulnerable critical care patient populations.
      A literature review was conducted to determine the evidence supporting the use of
      smart pumps for preventing medication errors. Cinahl and Medline databases from
      January 2003 through July 2008 were searched for English-language publications on
      the use of smart pumps and medication errors. Review of these publications
      revealed that well-designed research is still lacking with respect to the
      effectiveness of smart pumps in preventing medication errors. Nevertheless,
      findings indicate new directions for clinical practice and future research.

PMID- 20038876
TI  - Update on the treatment and management of patients with hepatitis.
AB  - Hepatitis is an inflammation of the liver that can be mild to life-threatening,
      based on the causative agent. Hepatitis viruses A through G are described along
      with potential treatments and infusion therapies. Nonviral causes of hepatitis
      include autoimmune, toxic, drug-induced, and alcoholic. The role of the infusion
      nurse is critical in prevention, patient education regarding all aspects of the
      condition, and administering and monitoring appropriate therapy.

PMID- 20038877
TI  - Intravenous administration of antineoplastic drugs: review of basics and what's
      new in 2009.
AB  - Today, newer treatment regimens combine chemotherapy with targeted therapy, based
      on an improved understanding of cancer pathophysiology. New diagnostic testing
      with microarray technology is helping to identify mutational sequences in patient
      tumors, so individualized treatment of cancer will occur during our lifetime. The
      administration of IV antineoplastic drugs continues to be an important role of
      infusion nurses. In addition, this therapy has also found a niche in the
      treatment of nonmalignant conditions such as rheumatoid arthritis. This article
      reviews the fundamentals of administration of IV antineoplastic drugs and current
      issues and trends.

PMID- 20038879
TI  - New PICC combines the power of PASV and power injection.

PMID- 20038880
TI  - Burning mouth syndrome: an update.
AB  - Burning mouth syndrome (BMS) refers to chronic orofacial pain, unaccompanied by
      mucosal lesions or other evident clinical signs. It is observed principally in
      middle-aged patients and postmenopausal women. BMS is characterized by an intense
      burning or stinging sensation, preferably on the tongue or in other areas of the
      oral mucosa. It can be accompanied by other sensory disorders such as dry mouth
      or taste alterations. Probably of multifactorial origin, and often idiopathic,
      with a still unknown etiopathogenesis in which local, systemic and psychological
      factors are implicated. Currently there is no consensus on the diagnosis and
      classification of BMS. This study reviews the literature on this syndrome, with
      special reference to the etiological factors that may be involved and the
      clinical aspects they present. The diagnostic criteria that should be followed
      and the therapeutic management are discussed with reference to the most recent
      studies.

PMID- 20038881
TI  - Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary
      alveoloplasty.
AB  - OBJECTIVE: Cleft lip and palate is a congenital facial malformation with an
      established treatment protocol. Mixed dentition period is the best moment for
      correct maxillary bone defect with an alveoloplasty. The aim of this surgical
      procedure is to facilitate dental eruption, re-establish maxillary arch, close
      any oro-nasal communication, give support to nasal ala, and in some cases allow
      dental rehabilitation with osteointegrated implants. STUDY DESIGN: Twenty cleft
      patients who underwent secondary alveoloplasty were included. In 10 of them
      autogenous bone graft were used and in other 10 autogenous bone and platelet-rich
      plasma (PRP) obtained from autogenous blood. Bone formation was compared by
      digital orthopantomography made on immediate post-operatory and 3 and 6 months
      after the surgery. RESULTS: No significant differences were found between both
      therapeutic groups on bone regeneration. CONCLUSION: We do not find justified the
      use of PRP for alveoloplasty in cleft patients' treatment protocol.

PMID- 20038882
TI  - Burkitt's lymphoma: a child's case presenting in the maxilla. Clinical and
      radiological aspects.
AB  - Burkitt's lymphoma (BL) is a neoplasm which, despite its very aggressive
      behaviour is potentially curable. It typically affects the paediatric population.
      BL belongs to the non-Hodgkin lymphomas group, and is the first human tumour
      undoubtedly related to a viral origin (Epstein-Barr virus). Two main clinical
      subtypes are recognized: endemic or African type, and sporadic type; HIV
      associated BL constitutes a third type. Although common in endemic BL, maxillary
      involvement is rare in sporadic cases. This, together with the clinical lack of
      specificity associated to this location, makes diagnosis difficult. New
      chemotherapeutic protocols achieve a high survival rate. Most important
      prognostic factors are location and tumour stage. We report a paediatric case of
      BL presenting in the maxilla, with a review and a description of the
      characteristics of the disease.

PMID- 20038883
TI  - Mucoceles of the oral cavity: a large case series (1994-2008) and a literature
      review.
AB  - OBJECTIVES: Evaluating data of patients affected by oral mucoceles, examined at
      the Unit of Oral Medicine and Pathology of the University of Milan between
      January 1994 and December 2008. STUDY DESIGN: Concise review on oral mucoceles
      and analysis of the clinical files of patients who underwent excisional biopsy
      (patient age, medical history, diagnosis, date and site of the biopsy,
      histopathological diagnosis and recurrences if any). RESULTS: During the period
      June 1994-December 2008, 158 mucoceles were observed (93 males and 65 females),
      with the most frequent site being the lower lip (53%) (p=0.001 by Fisher's test).
      The mean age of the patients was 31.9 years, with a peak of occurrence in the
      first four decades of life (75%). CONCLUSIONS: Mucoceles are lesions commonly
      seen in an oral medicine service, mainly affecting young people and lower lips.

PMID- 20038884
TI  - Histological evaluation of the effect of low-level laser on distraction
      osteogenesis in rabbit mandibles.
AB  - OBJECTIVES: This study evaluated the action of low level laser therapy (LLLT) on
      the percentage of newly formed bone in rabbit mandibles that underwent
      distraction osteogenesis (DO). STUDY DESIGN: Ten rabbits underwent bone
      lengthening according to the following protocol: Latency - 3 days; Activation - 7
      days 0.7 mm/d; and Consolidation - 10 days. The control group was composed of 4
      rabbits. The experimental group, composed of 6 rabbits, received infrared GaAlAs
      LLLT (wavelength=830 nm, P=40 mW) according to the following protocol: point dose
      of 10 J/cm(2) applied directly on the bone site that underwent DO during bone
      consolidation at 48-hour intervals. RESULTS: The percentage of newly formed bone
      was greater in the LLLT group (57.89%) than in the control group (46.75%)
      (p=0.006). CONCLUSION: The results suggest that LLLT had a positive effect on the
      percentage of newly formed bone. Better-quality bone sites may allow early
      removal of the osteogenic distractors, thus shortening total treatment time.

PMID- 20038885
TI  - Odontogenic cysts: demographic profile in a Brazilian population over a 38-year
      period.
AB  - OBJECTIVE: To determine the distribution of odontogenic cysts diagnosed
      histologically over a period of 38 years in a Brazilian population according to
      age, gender and site affected and to compare these data with previously reported
      studies from other countries. STUDY DESIGN: A total of 1019 cases of odontogenic
      cysts diagnosed between 1970 and 2007 were studied. Clinical features obtained
      from the patient records and microscope slides were reviewed according to the
      1992 World Health Organization classification. RESULTS: The mean age was 31.0
      years, and there was a predominance of females. The most frequent odontogenic
      cysts were radicular cysts (61.4%), followed by dentigerous cysts (20.1%) and
      odontogenic keratocysts (6.4%). Radicular cysts were more frequent in females
      (62.0%), and the maxillary teeth were the site most commonly involved (63.05%).
      The peak incidence of dentigerous cysts occurred in the second decade of life,
      with the posterior region of the mandible being the site most affected (46.3%),
      followed by the anterior region of the maxilla (27.8%). Odontogenic keratocysts
      showed a peak incidence between the third and fourth decades of life and
      predominance among females. The posterior region of the mandible was the site
      most frequently affected (65.6%). CONCLUSION: The present results showed a
      similar frequency of odontogenic cysts in this Brazilian population and other
      populations around the world, with inflammatory cysts being identified as the
      most frequent odontogenic cyst. Radicular cysts, dentigerous cysts, and
      odontogenic keratocysts are the most common cystic lesions, accounting for 87.9%
      of all odontogenic cysts.

PMID- 20038886
TI  - Wegener's granulomatosis: description of a case with oral manifestation.
AB  - Wegener's granulomatosis is a multisystemic granulomatous vasculitis that
      predominantly affects the airways and the kidneys, but may affect any organ.
      Otorhinolaryngological manifestations may be oral ulcers, gingival swelling or
      septal perforations that can cause saddle nose deformities, rhinitis, sinusitis
      and hearing loss. The oral ulcers usually occur when the disease is advanced.
      Renal involvement is characterized by focal and segmental glomerulosclerosis, and
      determines the evolution. The diagnosis is made by clinical symptoms and signs,
      the presence of c-ANCA and a positive biopsy. The anatomic pathology is
      characterized by vasculitis, granulomatous inflammation with multinuclear giant
      cells and necrosis. The prognosis has improved as a result of treatment with
      immunosuppressants associated with corticosteroids. We report a case of a 53-year
      old patient with Wegener's granulomatosis with oral manifestation, which began as
      chronic mastitis.

PMID- 20038887
TI  - Oral health survey of the adult population of the Valencia region (Spain).
AB  - OBJECTIVES: Ascertain the oral health status of the adult population in the
      Valencia region of Spain. STUDY DESIGN: A cross sectional prevalence study was
      conducted on a sample of 1264 adults, comprising 733 individuals aged 35-44 years
      and 531 individuals aged 65-74 years. Data collection was carried out in 2006. In
      both age groups (younger adults and older adults), the clinical examinations were
      carried out by calibrated dentists (Kappa <0.76). RESULTS: The caries prevalence
      in the group of 35-44 year-old subjects was 92.2% (DMFT=7.64). In the group of 65
      74 year-old subjects, it was 98.3% (DMFT=16.38). The F/DMFT percentage of the
      younger adults was 66% and that of the older adults was 16.3%. The edentate
      percentage was 0.1% in the group of 35-44 year-old subjects and 20.7% in the
      group of 65-74 year-old subjects. Calculus prevalence was almost 60% among the
      younger adults. Nearly 22% of the younger adults and 26% older adults presented
      periodontal pockets, although only a minority (4.6% and 4.3%) were CPI score 4.
      Significant differences in the various indices were found in relation to
      institutionalization and socio-economic status. CONCLUSIONS: The caries
      prevalence (DMFT>0) found in the two age groups studied remains very high: over
      90%. The worst health status is found in certain groups, such as the
      institutionalized elderly and adults with a low socio-economic status.

PMID- 20038888
TI  - Pre-operative evaluation of the volume of bone graft in sinus lifts by means of
      CompuDent.
AB  - OBJECTIVE: This study aims to evaluate the usefulness of the CompuDent program in
      determining the pre-operative volume of bone graft in maxillary sinus floor
      lifts, and to calculate the volume of graft necessary for rehabilitation using
      varying lengths of implants. STUDY DESIGN: Based on the CompuDent program, we
      calculated the volume of graft necessary for 47 sinus lifts. This volume was
      measured in order to raise the floor of each sinus to 13.4 and 15 mm in height.
      RESULTS: The average volume of graft in order to achieve a lift of 13'4 mm was
      2.42 cm(3) for the right maxillary sinus, with a range from 1.4 cm(3) to 4.1
      cm(3), and 2.50 cm(3) for the left maxillary sinus, with a range from 1.04 cm(3)
      to 3.79 cm(3). The average volume of graft in order to achieve a lift of 15 mm
      was 3.01 cm(3) for the right maxillary sinus, with a range from 1.78 cm(3) to
      4.59 cm(3), and 3.09 cm(3) for the left maxillary sinus, with a range from 1.42
      cm(3) to 4.49 cm(3). The statistical results provided by the Pearson Correlation
      show a significant inversely proportional correlation between the average of the
      heights and the volume of graft in the sinus. In addition, there is a clear
      correlation between the average volumes to be grafted for the respective heights
      13.4 mm and 15 mm. CONCLUSIONS: The CompuDent program is an effective tool in
      determining the volume of bone graft given its simplicity, rapidness and
      possibility of standardization in all pre-surgical procedures.

PMID- 20038889
TI  - Delayed removal of a maxillary third molar from the infratemporal fossa.
AB  - Removal of an impacted superior third molar is usually a simple and uncomplicated
      procedure for an Oral and Maxillofacial Surgeon. Nevertheless, complications are
      possible and include infection, facial swallowing, trismus, wound dehiscence,
      root fracture or even orosinusal fistula. Iatrogenic displacement into the
      infratemporal fossa is frequently mentioned but rarely reported. This anatomical
      fossa includes several important structures such as the internal maxillary
      artery, the venous pterygoid plexus, the sphenopalatine nerve, the coronoid
      process of the mandible and the pterygoid muscles. Recommended treatment includes
      immediate surgical removal if possible or initial observation and secondary
      removal, as necessary, because of infection, limited mandibular movement,
      inability to extract the tooth, or the patient's psychological unease. Sometimes,
      the displaced tooth may spontaneously migrate inferiorly and becomes accessible
      intraorally. This report describes the location and secondary surgical removal of
      a left maxillary third molar displaced into the infratemporal fossa, two weeks
      after first attempt at extraction.

PMID- 20038890
TI  - Multifocal epithelial hyperplasia, a rare oral infection in Asia: report of
      twelve cases in Iran.
AB  - OBJECTIVES: Multifocal epithelial hyperplasia (MEH) is benign, asymptomatic oral
      disease with viral etiology. The frequency of this disease varies widely from one
      geographic region to another, and can vary, from 0.002 to 35% depending on the
      population studied. STUDY DESIGN: Here we report the clinicopathological features
      of twelve cases of MEH referred to Oral Medicine Department of Mashhad Dental
      School for the first time in Iran. Records of patients with the diagnosis of MEH
      in our department during 7 years were analyzed and data were extracted. RESULTS:
      Most of the patients were younger than 20-year-old (66%), and females were
      predominantly affected (7:12). The mean age of onset was 12.72+/-10.14 years and
      the mean duration was 52.54 +/- 78.51 months. Patients had multiple, well
      circumscribed, soft, non tender, flattened papules, with a color similar to the
      adjacent mucosa, in different areas of the oral cavity but the most affected site
      was buccal mucosa. Familial history of such lesions was negative in all patients.
      Only three cases showed spontaneous regression. CONCLUSION: In spite of rare
      nature of this disease in Asia, it seems that it is not the case in Khorasan
      Province, southeast Iran.

PMID- 20038891
TI  - Panoramic and tomographic implant studies: role in the diagnosis of sinus
      disorders.
AB  - OBJECTIVE: To study the presence of sinus disorders and their diagnosis based on
      clinical and radiographic findings, correlating their presence with tomography
      tests and panoramic radiography. STUDY DESIGN: We conducted a retrospective study
      on 152 patients who were seeking implant treatment, thereby allowing us to
      evaluate 42 patients who had abnormal sinuses. The patients underwent an
      evaluation of their medical history as well a clinical examination, panoramic
      radiography and tomographic study. RESULTS: The average age of the patient was
      59.8 years old, and 54.76% of the group were males and 45.23% were females. Prior
      respiratory disorders were present in 52.38% of the patients, and 57.3% of the
      group presented dental disorders. In assessing the type of wound, we observed
      that 73.21% were mucosal hyperplasia and 26.78% were mucous cysts. Of the 56
      sinuses affected, only 28.57% were diagnosed using panoramic radiography.
      CONCLUSIONS: Panoramic radiography has limitations in the diagnosis of sinus
      disorders; computerized tomography (CT) remains the most effective diagnostic
      test.

PMID- 20038892
TI  - Microstructure alterations of rotary files after multiple simulated operative
      procedures.
AB  - AIM: to assess morphological alterations of ProTaper rotary NiTi files before and
      after continuous use by scanning electron microscopy (SEM). STUDY DESIGN: 30 root
      canals were chosen with an angle between 15 and 30 degrees . Before starting to
      prepare the canals the files were observed microscopically using a scanning
      electronic microscope. The ProTaper sequence recommended by the manufacturer was
      used, with NaOCl as irrigant. The instruments were sterilised after every three
      canals were shaped. The instruments were observed with the same microscope after
      shaping each canal, until 30 root canals were shaped. The criteria used for
      checking the instruments were: blunt cutting edges, disruption of cutting edge,
      microfractures, fatigue cracks, metal flash, dentine remains. RESULTS: Many
      microscopic defects were found such as: cutting edge breaks (up to 70%); fatigue
      cracks, between 33 and 100%. No microfractures were found. An S1 and an SX file
      were fractured. CONCLUSION: ProTaper instruments are quite reliable if used
      following usual requirements.

PMID- 20038893
TI  - A clinical longitudinal study 323 porcelain laminate veneers. Period of study
      from 3 to 11 years.
AB  - OBJECTIVE: The objective of this study was to evaluate the clinical results of
      323 porcelain laminate veneers over a period of 3 to 11 years. MATERIAL AND
      METHOD: This study included 70 patients, aged between 18 and 74 years. Of the 323
      total veneers, 124 were of a simple design and 199 were of a functional design.
      The condition of the soft tissues and hygiene, in addition to the condition of
      the abutment teeth, the restorations and patient satisfaction were all clinically
      examined. In carrying out the statistical analysis, a descriptive approach was
      taken in analyzing the data. The Kaplan Meier method was used for statistically
      analyzing the survival rates of the porcelain laminate veneers. RESULTS: Analysis
      of the soft tissue revealed marginal recession in 7.7% of the cases, and in 21.6%
      of the cases, bleeding was detected on probing. Analysis of the condition of the
      abutment teeth revealed secondary caries and hypersensitivity in 3.1% of the
      cases, and changes in pulp vitality were observed in 2.8% of the cases. In
      studying the condition of the restorations, marginal integrity was observed to be
      excellent in 98% of the cases, slight marginal pigmentation was present in 39.3%
      of the cases, fractures were present in 4% of the cases and decementation in 9%
      of the cases. The degree of patient satisfaction was considered to be excellent
      in 97.1% of the cases. CONCLUSIONS: Porcelain laminate veneers are a predicable
      treatment option that offer excellent results.

PMID- 20038894
TI  - Myofibroma of the oral cavity. A rare spindle cell neoplasm.
AB  - Myofibroma is an uncommon spindle cell neoplasm rarely found in oral cavity.
      Typically, this lesion is seen in neonates and infants with few cases reported in
      adults patients. In the oral cavity, myofibroma occurs within the submucosal or
      intramuscular tissue and has a predilection by the tongue, buccal mucosa and
      lips. Microscopically, a typical biphasic pattern can be observed. Misdiagnosis
      included benign and malignant spindle cell lesions of nerve tissue or smooth
      muscle origin, such as neurofibroma, leiomyoma and sarcomas. Thus,
      immunohistochemical staining is a useful tool to identify the nature of
      neoplastic cells and to reach an accurate diagnosis. An immunohistochemical panel
      consisting of antibodies to vimentin, SMA, HHF-35, S-100p and desmin must be
      achieved. In most cases, positivity for vimentin, SMA and HHF-25 can be observed.
      Our report describes a solitary myofibroma of the tongue of a 23-year-old man
      with emphasis in clinical, histopathological and immunohistochemical features of
      this lesion.

PMID- 20038895
TI  - Study of lip hydration with application of photoprotective lipstick: influence of
      skin phototype, size of lips, age, sex and smoking habits.
AB  - OBJECTIVES: To study lip hydration levels when applying a lipstick sunscreen for
      3 months and to evaluate the influence of size of lips, age, sex, smoking and
      skin phototype. STUDY DESIGN: The study group was formed by 140 volunteer
      subjects, one group consisting of 70 patients applying a commercial lipstick
      sunscreen three times a day and the other group of 70 controls in which no
      product was applied. The age range was 20-86 years. The influence in lip
      hydration levels of age, sex, phototype, size of the lips and smoking habits was
      studied using a Corneometer 825 (Courage & Khazaka Electronic GmbH, Cologne,
      Germany). RESULTS: An increase in lip hydration was found between the basal
      (53.49 +/- 15.259) and final (59.34 +/- 14.51) Corneometer 825 (Courage & Khazaka
      Electronic GmbH, Cologne, Germany) measurements over the three months of
      treatment, with statistically significant differences with respect to the control
      (p=0.002). However, no statistically significant differences in lip hydration
      were observed with regard to age, (p=0.48), gender (p=0.876), skin phototype
      (p=0.653), lip area (p=0.291) and smoking (p=0.178). CONCLUSIONS: Application of
      a lipstick sunscreen 3 times a day for 3 months increases lip hydration.

PMID- 20038896
TI  - Effects of polyglecaprone 25, silk and catgut suture materials on oral mucosa
      wound healing in diabetic rats: an evaluation of nitric oxide dynamics.
AB  - OBJECTIVES: The purpose of this study is to investigate the effects of monocryl
      (Polyglecaprone 25), silk and catgut suture materials on wound healing in
      diabetic rats and to evaluate NO (nitric oxide) dynamics. STUDY DESIGN: Fourty
      eight male Wistar-Albino rats weighing 220-270 g were used in this study. The
      rats were categorized into 2 groups, as control group (n=24) and streptozotocin
      (STZ) induced diabetic group (n=24). For each group, incision wounds were created
      on the inner cheek mucosa of the animals and wounds were closed primarily with
      three different types of sutures. These materials were sized 3-0 monocryl
      (polyglecaprone 25), silk and catgut sutures swaged on. Excisional biopsies were
      performed at 2nd, 7th, 14th and 21st day (2 rats per day) from the initial
      surgical procedure. Effects of these suture materials on wound healing and NOS
      (nitric oxide synthase) activities were compared immunohistochemically in the
      study. eNOS and iNOS (Endothelial and induced nitric oxide synthase) activities
      were classified as mild (+), moderate (++) and severe (+++). RESULTS: Mild eNOS
      activities were seen in both diabetic and control groups at 2nd day specimens.
      Activities of silk and catgut were similar both in diabetic and control groups at
      14th day, this activity in monocryl was mild. 21st day specimens revealed that
      monocryl has mild eNOS activity than silk and catgut sutures. iNOS activities in
      diabetic group were greater than control groups and the degrees of the activity
      in monocryl, silk and catgut sutures were mild, severe and moderate at the 7th
      day. At the 14th day there was no iNOS activity in diabetic monocryl group.
      CONCLUSION: All of the materials have the potential capacity to be well tolerated
      however monocryl seemed to have more beneficial effects on wound healing in
      diabetic subjects.

PMID- 20038897
TI  - Full maxillary rehabilitation with an all-ceramic system.
AB  - With the appearance of all-ceramic systems, providing a choice of framework
      porcelains and allowing the same material to be used for the veneer, it is now
      possible to select the ideal structure in terms of both function and aesthetics.
      Silicate ceramics allow porcelain laminate veneers and crowns to be used in the
      anterior region, providing excellent aesthetics; while for the posterior area,
      where function takes precedence, oxide ceramics, specifically zirconium oxide,
      are preferred. The IPS e.max ceramic system, heir-apparent to the IPS Empress 2
      system, combines the advantages of zirconium oxide ceramics (IPS e.max Zircad)
      with the excellent aesthetic qualities of silicate ceramics (IPS e.max Press).
      This paper presents a clinical case requiring complete maxillary rehabilitation
      for aesthetic purposes. An overview of some of the porcelains used in this
      system, analyzed from both the clinical and laboratory perspective is provided.
      The aesthetic advantages of a single ceramic veneer, the need to select
      appropriate ceramics for anterior and posterior regions, and cementation and
      surface treatments are discussed.

PMID- 20038898
TI  - Biomaterials for bone regeneration.
AB  - OBJECTIVE: This article reviews the literature on biomaterials used for bone
      regeneration. MATERIAL AND METHOD: A total of seventeen bibliographic sources
      were found using the MEDLINE database and to avoid the variability of the search
      terms the thesaurus Mesh was used. RESULTS: These materials act essentially due
      to their osteoconductive ability, although their osteoinductive capacity is being
      improved with the use of growth factors. As to their effectiveness, many
      differences exist between them and some even affect bone regeneration negatively.
      CONCLUSIONS: Biomaterials used for bone regeneration are valid when the correct
      material is used. As yet the osteogenic capacity of autogenous bone has not been
      equalled by biomaterials. Tissue engineering has caused great interest because of
      its many possibilities, although more studies are necessary in order to achieve
      the ambitious expectations when it comes to tissue or organ regeneration in the
      human body.

PMID- 20038899
TI  - Etiology, risk factors and management of implant fractures.
AB  - Implant fracture is an infrequent and late biomechanical complication with a
      serious clinical outcome. In effect, such fractures pose important problems for
      both the patient and the dental surgeon. According to most literature sources,
      the prevalence of dental implant fractures is very low (approximately 2 fractures
      per 1000 implants in the mouth). Considering that implant placement is becoming
      increasingly popular, an increase in the number of failures due to late fractures
      is to be expected. Clearly, careful treatment can contribute to reduce the
      incidence of fracture. An early diagnosis of the signs alerting to implant
      fatigue, such as loosening, torsion or fracture of the post screws and prosthetic
      ceramic fracture, can help prevent an undesirable outcome. The present literature
      review describes the management options and discusses the possible causal
      mechanisms underlying such failures, as well as the factors believed to
      contribute to implant fracture.

PMID- 20038900
TI  - Knowledge of oral cancer and preventive attitudes of Spanish dentists. Primary
      effects of a pilot educational intervention.
AB  - OBJECTIVE: To assess the knowledge and preventive attitudes that Spanish dentists
      have towards oral cancer, before and after an educational intervention. METHODS:
      A quasi-experimental study based on a nationwide intervention. All Spanish
      dentists were offered an on-site course on oral cancer. An individual
      questionnaire was administered before and after attending the course. The main
      outcome measures were systematic examination of the oral cavity, promotion of
      healthy habits and knowledge of clinical aspects. RESULTS: 440 GDPs entered the
      study. Age: 40.7+/-10.7, range 21-74. Professional experience: 13.9+/-8.9 years,
      range 0-45. Of those who participated in the study, 53.1% had never attended a
      course on oral cancer, 72.4% stated that they perform a systematic examination of
      the oral mucosa, 88.2% provided systematic counselling on tobacco cessation, and
      54.7% reported that they did the same for alcohol. In addition, 32.3% advised
      patients to eat fruits and vegetables high in antioxidants. Professional
      experience was significantly associated with oral mucosa systematic examination
      (t= 2.9; p=0.003), advice on alcohol consumption (t=5.0; p=0.000), and on fruit
      and vegetable intake (t=5.1; p<0.001). None of these practices were specifically
      associated with knowledge on oral cancer. All areas of knowledge examined showed
      statistically significant improvement after the educational intervention.
      CONCLUSIONS: The intervention appears to have improved the GDP s knowledge,
      confirming the importance of this national campaign.

PMID- 20038901
TI  - Oroantral communications. A retrospective analysis.
AB  - OBJECTIVE: To analyze characteristics, clinical evolution and surgical techniques
      of oroantral communication (OAC). STUDY DESIGN: We included all patients operated
      at the University Central Hospital (Oviedo, Spain) between 1996 and 2007. The
      variables assessed were age, sex, medical history, OAC size, sinus disease,
      surgical technique, duration of hospitalization and post-surgical evolution.
      RESULTS: We analyzed 12 patients (7 men and 5 women) with an average age of 47.5
      years. The most frequent cause of oroantral communication was the extraction of
      the first upper molar. The average size of fistula was 0.9 cm. Buccal flap repair
      was used in 7 patients, palatal rotation-advancement flap in 4 patients and
      buccal fat pad in only one patient. Suture dehiscence was observed in one patient
      treated with a palatal flap, but no additional surgery was required. Three OAC
      recurred; all of them following a buccal flap procedure. All recurrences
      spontaneously closed between one and four months following the procedure.
      CONCLUSIONS: OACs are rare complications and treatment should be individualized
      to avoid further complications.

PMID- 20038902
TI  - Oro-facial aspects of leprosy: report of two cases with literature review.
AB  - Leprosy is a chronic infectious disease affecting primarily the skin, peripheral
      nerves, respiratory system and the eyes. Leprosy induces various types of
      clinical presentation affecting the patient's immune response. Cell-mediated
      immunity is considered to be the crucial defence against the disease and the
      magnitude of this immunity defines the extent of the disease. The article
      presents two case reports of manifestations of leprosy in the oro-facial region,
      with a brief review of various other important oro-facial manifestations of
      leprosy. The first report deals with granulomatous nodules in the palate while
      the second report presents bilateral facial palsy in leprosy patients. Both the
      reports gain importance due to rare oral manifestation in a borderline leprosy
      patient in the first case, while the second case presents a rare bilateral Bell's
      sign. The role of the dental profession and especially the Oral Medicine
      specialist is of great importance in early diagnosis of oral lesions.

PMID- 20038903
TI  - The prevalence of root dilacerations in a Turkish population.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of root
      dilaceration in a Turkish dental patient population, considering factors such as
      dental localization and the relationship between the sexes in this anomaly. STUDY
      DESIGN: A retrospective study was performed using periapical radiography of 2,124
      patients, who ranged in age from 15 to 65 years old. All data (age, sex and
      systemic disease or syndrome) were obtained from the patient files and analyzed
      for root dilaceration. Descriptive characteristics of sexes, jaws, and dental
      localization were recorded. The Pearson chi-squared test was used. RESULTS: Of
      the 2,251 patients, 214 (9.5%) were found to have root dilaceration. Root
      dilacerations were determined in 276 (4.3%) of 6386 teeth, belonging to a total
      of 2251 patients. Anomalies were found in 9.8% of males, compared with 9.3% of
      females, a difference that was not statistically significant (p>0.05). Root
      dilacerations were distributed fairly evenly between the maxilla and mandible.
      The most frequently root dilacerated teeth were found to be mandibular third
      molars (12.8%), followed by maxillary third molars (7.4%), and maxillary first
      molars (6.7%). Root dilaceration was not detected in maxillary central incisors,
      mandibular central incisors or mandibular lateral incisors. CONCLUSION: root
      dilaceration is an uncommon developmental anomaly which occurs mostly in the
      posterior teeth, which are not prone to suffer trauma. The radiographic diagnosis
      of this anomaly is important before surgery, and especially before endodontic
      treatment or orthodontic treatment.

PMID- 20038904
TI  - Assessing the determination of salivary electrolytes and anti-Ro and anti-La
      antibodies for the diagnosis of Sjogren's syndrome (SS).
AB  - The aim of this study was to assess changes in salivary electrolyte flow and
      composition and the presence of anti-Ro/SSA and anti-La/SSB serum and saliva
      antibodies and their implications for the non-invasive diagnosis of SS. STUDY
      DESIGN: 73 patients were studied, divided into the following experimental groups:
      primary Sjogren syndrome (SSp) (n=15), secondary SS (SSs) (n=17), dry mouth, dry
      eye without Sjogren's syndrome (BO) (n=20) and healthy controls (C) (n=21). We
      conducted a baseline assessment of salivary flow and saliva sampling for the
      measurement of sodium, chlorine, potassium, calcium and phosphate electrolytes,
      and the determination of anti-Ro/SSA and La/SSB antibodies; a serum sampling was
      made to assess antibody positivity. RESULTS: Salivary flow in SSp, SSs and BO was
      significantly lower (p<0.001) relative to C. The salivary composition of SS
      showed an increase of inorganic components. Anti-Ro/SSA and anti-La/SSB
      antibodies occurred more frequently in serum and saliva in SS patients compared
      with BO and C, with higher frequency of positivity in serum compared with saliva.
      CONCLUSION: Our results suggest new tools that could aid the non-traumatic
      diagnosis of the origin of hyposalivation.

PMID- 20038905
TI  - Diagnostic of craniofacial asymmetry. Literature review.
AB  - Facial asymmetry is a common feature in many syndromes, and requires surgery as
      the only valid treatment option. Routine diagnostic methods (frontal RX,
      panoramic RX and submentovertex RX) have serious limitations mainly due to the
      transfer from a three dimensional image to a two dimensional plane. The
      feasibility of such methods is poorly supported due to inherent projection errors
      (image magnification, cranial rotation) and identification errors (image quality,
      precision and reproducibility). The use of computer tomographies represents a
      substantial improvement in the sense of skeletal and soft tissue structures'
      reproduction precision. The interpretation of this new data source makes evident
      the necessity of new analysis tools for extraction, manipulation and
      synthesization of the whole diagnostic and therapeutical potential based on more
      solid studies in this field.

PMID- 20038906
TI  - Cri du chat syndrome: a critical review.
AB  - A new syndrome was identified in 1963, when Lejeune et al. reported a genetic
      disease resulting from a partial or total deletion on the short arm of chromosome
      5 (5p-) and named it the cri du chat syndrome (CdCS). This term makes reference
      to the main clinical feature of the syndrome, a high-pitched monochromatic cat
      like crying, that usually disappears in the first years of life. CdCS is one of
      the most common chromosomal deletion syndromes in humans, with an incidence of
      1:15.000-1:50.000 live-births. Our purpose was to review different aspects of
      this syndrome (concept, epidemiology, aetiology, clinical features, diagnostic
      methods and prognosis) emphasizing both: the breakthrough in this field
      introduced by new cytogenetic and molecular techniques, and the orofacial
      manifestations most frequently reported. The main orofacial anomalies registered
      were mandibular microretrognathia, high palate but rarely cleft, variable
      malocclusion (frequently anterior open-bite), enamel hypoplasia, poor oral
      hygiene, generalized chronic periodontitis, and retardation of tooth eruption,
      although there is not enough evidence to support any clear association between
      these pathologies and the CdCS.

PMID- 20038907
TI  - Screening for hypertension in a primary care dental clinic.
AB  - OBJECTIVE: The aim of this study was to record blood pressure in patients during
      their visit to a dental clinic, with the aim of identifying those who have high
      blood pressure and are unaware of it, as well as those who are aware of their
      condition but do have their blood pressure under adequate control. STUDY DESIGN:
      We designed a cross-sectional study which included 154 patients who were seen for
      a dental checkup at the Primary Dental Care of the Gallician Health Service
      (SERGAS). All participants completed a standardized medical questionnaire after
      measuring their systolic blood pressure (SBP) and diastolic blood pressure (DBP),
      which was conducted using the protocol established by the Spanish Society of
      Hypertension-Spanish League for the Fight Against Hypertension (HTA). RESULTS: In
      45 patients (29%), the figures for blood pressure were recorded as SBP>or=140
      mmHg and/or DBP>or=90 mmHg, indicating that they may have hypertension. Only 12
      of them had been previously diagnosed with hypertension, but did not have their
      blood pressure under adequate control. The remaining 33 had no history of
      hypertension and were referred to a family physician, but only 19 saw their
      doctor; 11 of these patients were given non-pharmacological treatment, 6 were
      prescribed drug treatment and no type of treatment was indicated for the other
      two patients. CONCLUSIONS: By screening for hypertension, especially among
      patients who are more than 40 years old, the dentist can play an important role
      in the early diagnosis.

PMID- 20038908
TI  - Immunohistochemical expression of estrogens and progesterone receptors in
      carcinoma ex pleomorphic adenoma-undifferentiated and adenocarcinoma types.
AB  - Cancer of the salivary gland is one of the common cancers in the head and the
      neck regions. This type of cancer develops in the minor and the major salivary
      glands, and it sometimes metastasizes to other organs, particularly the lung.
      Morphologic mimicry and similarity in the expression of steroid hormone receptors
      between salivary gland tumours and breast tumours are well-known phenomena and
      are occasionally debated in the field of surgical pathology. The expression of
      sex hormone receptors in some tumours suggests a role for these receptors in
      tumor pathogenesis and therapy. Previous studies of the expression of estrogens
      and progesterone receptors in salivary gland tumours have reported conflicting
      results. OBJECTIVE: Our study aimed to characterize alteration in the
      immunohistochemical expression of oestrogens receptor and progesterone receptor
      in the tumour cells of carcinoma arising in pleomorphic adenoma. STUDY DESIGN: 27
      cases of carcinoma arising in pleomorphic adenoma (undifferentiated and
      adenocarcinoma types) were examined. RESULTS: The results showed that 27 (100 %)
      of 27 cases had negative nuclear staining for either oestrogens or progesterone
      receptors. CONCLUSION: Our data suggest that carcinomas arising in pleomorphic
      adenoma were not dependent on endocrine function.

PMID- 20038909
TI  - Importance of cone beam computed tomography for diagnosis of calcifying cystic
      odontogenic tumour associated to odontoma. Report of a case.
AB  - The calcifying cystic odontogenic tumour (CCOT) is a rare benign cystic neoplasm
      not infrequently associated with odontoma. This report documents a case of CCOT
      associated with compound odontoma arising in the anterior maxilla in a 25-year
      old woman. Conventional radiographs showed a large calcified mass with poorly
      visualized radiolucent margins. The extent and condition of the internal
      structure of the CCOT associated with odontoma was able to be determined based on
      radiographic findings from cone beam computed tomography. This advanced image
      technique proved to be extremely useful in the radiographic assessment of this
      particular neoplasm of the jawbones.

PMID- 20038910
TI  - Specific (granulomatous) oral lesions of sarcoidosis: report of two cases.
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown aetiology that
      usually presents with bilateral hiliar adenopathies, pulmonary infiltrations, and
      ocular and cutaneous lesions. The specific cutaneous lesions, or granulomatous,
      are produced in from 9% to 37% of patients with systemic sarcoidosis.
      Nevertheless, few patients have been described having specific lesions from
      sarcoidosis in the oral mucous membrane. We present 2 patients with systemic
      sarcoidosis who developed specific sarcoidosis lesions in the oral mucous
      membrane. The first patient presented a plaque on the tongue of a chronic nature
      associated with facial lupus pernio. The second patient presented a rapidly
      growing nodular lesion on the lower lip that was in fact the presentation sign of
      the disease. Although infrequent, oral lesions may constitute the first sign of
      systemic sarcoidosis. For this reason the oral mucous membrane needs to be
      explored when there is suspicion of sarcoidosis, and systemic sarcoidosis must be
      included in the differential diagnosis of oral granulomatous lesions.

PMID- 20038912
TI  - Salivary and serum levels of substance P, neurokinin A and calcitonin gene
      related peptide in burning mouth syndrome.
AB  - BACKGROUND: Burning mouth syndrome (BMS) is an enigmatic condition with the
      aetiopathogenesis remaining largely obscure. However, a neuropathic basis for BMS
      continues to be an area of active clinical and research interest. AIM: It is
      becoming increasingly evident that certain oral disorders may be modulated by
      imbalances in certain neuropeptides such as substance P (SP), neurokinin A (NKA)
      and calcitonin gene-related peptide (CGRP) therefore we measured SP, NKA and CGRP
      in the saliva and sera of BMS patients as well as controls. SUBJECTS AND METHODS:
      Salivary and serum SP, NKA and CGRP were determined in the 26 female patients
      with burning mouth syndrome (age range 51-78, mean 65.69 yrs), and in the 22
      female controls (age range 24-82, mean 49.72 yrs). Serum and salivary SP, NKA,
      CGRP levels were determined by commercial competitive enzyme immunoassay kits.
      Statistical analysis was performed by use of descriptive statistics and analysis
      of variance. RESULTS AND CONCLUSIONS: No significant differences in salivary SP,
      NKA and CGRP as well as serum SP and CGRP between BMS patients and controls could
      be found. However, significantly decreased serum neurokinin A (p<0.05) in BMS
      patients may reflect an inefficient dopaminergic system.

PMID- 20038913
TI  - Basaloid squamous cell carcinoma: report of five cases.
AB  - OBJECTIVES: To document the clinical and histopathological characteristics of
      basaloid squamous cell carcinoma (BSCC). To add five new cases to the literature
      and compare them with another published series. CASES: retrospective review of
      five cases with the diagnosis of BSCC of the larynx. RESULTS: all the patients
      were male. They were heavy smokers and drinkers. Most of the tumours were
      supraglottic. Three patients presented with stage-IV disease and the other two
      with stage-I disease. Surgery supplemented with radiation was used in three
      patients, partial surgery was used in another case and radiation and associated
      chemotherapy in the other one. Eight neck dissections were performed, six of them
      were functional and the other two radical dissections. Two cases were found to
      have metastatic lymph nodes. There were not any distant metastases but two
      patients had tumoral relapse. CONCLUSIONS: BSCC has well defined histological
      features. Central comedonecrosis within the cells nests, cell with nuclear
      palisading and high-grade dysplasia in overlaying mucosa are the main
      characteristics.

PMID- 20038911
TI  - A comparative study of platelet-rich plasma, hydroxyapatite, demineralized bone
      matrix and autologous bone to promote bone regeneration after mandibular impacted
      third molar extraction.
AB  - OBJECTIVES: 1) to compare mandibular bone regeneration by applying autologous
      bone, platelet-rich plasma and two biomaterials (synthetic calcium
      hydroxyapatite, and demineralized bone matrix), and thus establish the potential
      benefits of these biomaterials in the regeneration of postextraction alveolar
      bone, 2) to identify which of them accelerates more bone regeneration and 3) to
      determine whether there are differences in the postoperative period (pain,
      swelling, trismus, infection) depending on the material used. STUDY DESIGN: It
      consists in a prospective, controlled (with a split- mouth design) and double
      blinded study. We use as a model an easily reproducible non-critical bone defect:
      the defect that remains after extraction of mandibular impacted third molar. The
      study design is based on the extraction of two mandibular impacted third molars
      in a patient during the same surgical procedure by the same surgeon. We assessed
      postoperative clinical data, and short, medium and long term neoformation of
      alveolar bone after extraction. We compared the two sockets (right and left),
      which had been grafted in a different way with the various elements mentioned
      above. In addition, we compared the postoperative inflammatory symptoms between
      groups. RESULTS: The highest acceleration in bone formation was observed in
      groups in which we used autologous bone and demineralized bone matrix. There were
      no statistically significant differences between groups regarding pain, swelling,
      trismus and infection throughout the postoperative period. CONCLUSIONS: According
      to the results of our study, autologous bone persists as the gold standard
      material for bone regeneration. Among the assessed biomaterials, demineralized
      bone matrix has yielded the best results obtained. No significant differences in
      the postoperative (pain, swelling, trismus and infectious events) were observed,
      depending on the type of material used as a graft.

PMID- 20038914
TI  - Orthodontic management in patients with haemophilia. About two clinical cases.
AB  - The most common congenital bleeding disorder is haemophilia. It is a pathology
      inherited and caused by a defective or an absence of the coagulation factors, so
      that haemophiliacs cannot form an efficient clot. These patients have been
      treated with fear in the dental profession without having achieved the goals and
      ideals most appropriate according to the requirements of each case, which is
      demonstrated in the little existing literature available. However, they are
      currently treated as healthy orthodontic patients thanks to the advances in
      orthodontics. We present the cases of two brothers with mild classical
      haemophilia, who were treated by Mc Namara's disjunctor. The emphasis is on
      importance of interconsultation with the haematologist, prevention and oral
      hygiene, and that of the beneficial effect of orthodontic.

PMID- 20038915
TI  - Intraoral epithelioid hemangioendothelioma: a case report and review of the
      literature.
AB  - The epithelioid hemangioendothelioma (EH) is an uncommon angiocentric neoplasm of
      borderline or intermediate malignant potential, between the hemangioma and
      conventional angiosarcoma. It is characterized by the proliferation of
      endothelial cells with epithelioid or histiocitoide morphology with vacuolated
      cytoplasm and occasional eosinophilic spindle cells. Shows potential for local
      recurrence as well as the ability to metastasize. Rarely affects the oral cavity,
      it have been described from 1975 until 2008 only 27 oral cases. Morphologically
      the EHs may be confused with other lesions, from a hemangioma to a squamous cell
      carcinoma, and thus immunohistochemical analysis is required. This paper reports
      the clinical and immunohistochemical characteristics of a case of EH in the
      gingiva of the tooth 35 of a 17 years-old-white-female. We present a review of
      the clinicopathological and immunohistochemical characteristics of the intraoral
      epithelioid hemangioendothelioma cases previously reported.

PMID- 20038916
TI  - Streptococcal bacteraemia in patients submitted to hematopoietic stem cell
      transplantation: the role of tooth brushing and use of chlorhexidine.
AB  - A retrospective evaluation of 73 consecutive recipients of hematopoietic stem
      cell transplantation (HSCT) was conducted to investigated the role of oral care
      and incidence of streptococcal bacteremia in patients submitted to hematopoietic
      stem cell transplantation. Patients were retrospectively evaluated and divided
      into group A (GA=38) and group B (GB=35). During hospitalization patients from GA
      performed oral hygiene daily with extra soft toothbrush and toothpaste besides
      performing mouth cleaning with an ethanol-free 0.12% chlorhexidine solution tree
      times a day. In contrast GB patients performed mouth cleaning with extra soft
      toothbrush and toothpaste, but no chlorhexidine was used. Using the Chi square
      test it was observed that all patients from GA presented negative blood culture
      for alpha-hemolytic Streptococcus viridans and Candida albicans and only 1
      patient without oral mucositis from GB presented positive blood cultures for
      Streptococcus intermedius (p=0.48). The results indicate that methodology used
      for oral care before the HSCT and the practice of tooth brushing during the
      period were effective in preventing streptococcal bacteremia. Moreover, our data
      suggest that the mouth cleaning with chlorhexidine during HSCT may be not
      mandatory.

PMID- 20038917
TI  - Immunohistochemical study of Langerhans cells in periapical lesions: correlation
      with inflammatory cell infiltration and epithelial cell proliferation.
AB  - AIM: The aim of this study is to determine the presence and distribution of
      Langerhans cells in periapical lesions, and correlate this with inflammatory cell
      infiltration and epithelial cell proliferation. MATERIAL AND METHODS: Seventy
      chronic dental periradicular lesions, obtained during periapical surgery from 70
      patients, were included in this study, including: 46 granulomas, 18 scar tissue
      and 6 periradicular cysts. Immunohistochemical staining was performed using the
      following markers: CD3 to analyze the inflammatory infiltrate, CD1a to determine
      the presence of Langerhans cells and Ki67 to analyze the epithelial cell
      proliferation. The CD1a immunostaining density was established following Cincura
      (2007) criteria, being classified ranging from intense (3), moderate (2),
      discrete (1) or no (0) immunostaining. CD3 and Ki67 staining was evaluated
      following the Liapatas et al. scale, as: 0) no cells stained; 1) weak stain or
      few cells stained (11-25%); 2) moderate staining or some cells stained (26-75%);
      3) intense staining or many cells stained (more than 76%). RESULTS: Langerhans
      cells were found in 32.8% of the periapical lesions being more intense in the
      epithelialized lesions. CD3 immunohistochemical staining was found in all
      lesions, but with different values in relation to histological subtypes. Ki67 was
      positive in all epithelialized lesions, although with a moderate staining.
      CONCLUSIONS: Langerhans cells appeared to be associated with T-lymphocyte
      infiltration and the proliferative potential of the epithelial tissue in
      periapical lesions.

PMID- 20038918
TI  - Epstein Barr Virus detection and latent membrane protein 1 in oral hairy
      leukoplakia in HIV+ Venezuelan patients.
AB  - PURPOSE: To determine the prevalence of Epstein Barr virus (EBV) in oral hairy
      leukoplakia lesions (OHL) in HIV+ Venezuelan patients. MATERIAL AND METHOD: In
      this case study, we evaluated 21 HIV+ adult patients with clinically present OHL
      lesions, 11 who were undergoing antiretroviral therapy, 10 who were not
      undergoing therapy and 10 HIV-negative adult patients with hyperkeratotic oral
      mucosal lesions. All of the subjects were assessed at the Infectious Disease
      Center, Faculty of Dentistry, Central University of Venezuela, and were
      clinically examined to detect oral mucosal lesions with the confirmed
      histopathologic diagnosis. Nested-PCR was used to determine the EBV infection and
      the latent membrane protein-1 (LMP-1) expression by immunohistochemistry.
      RESULTS: Of the subjects, 16/21 (76%) of the HIV+/AIDS patients tested positive
      for EBV, whereas 5/10 (50%) of the HIV-negative subjects tested positive for EBV.
      CONCLUSIONS: In the present study, a higher EBV prevalence was observed in HIV
      positive patients when compared to HIV-negative patients without oral hairy
      leukoplakia, confirming the etiologic role in this entity. The LMP-1 in OHL
      patients who were both HIV+ and EBV+ was highly expressed (60%) at the epithelial
      basal cells. No association between the alcohol and tobacco consumption was
      observed among the EBV-positive cases.

PMID- 20038919
TI  - Atraumatic maxillary sinus elevation using threaded bone dilators for immediate
      implants. A three-year clinical study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of sinus floor
      elevation using sequential bone dilators. MATERIALS AND METHODS: Thirty patients
      took part in the study (18 women and 12 men) with ages ranging between thirty-six
      and sixty-three years, selected according to inclusion and exclusion criteria,
      who showed a bone deficit in the upper posterior alveolar margin of 5-8 mm in
      height. Sixty expanded platform internal connection implants were placed with
      diameters of 4/5/4 mm and lengths varying between 10 (n=10) and 11.5 mm (n= 50).
      RESULTS: Data obtained were analyzed using SPSS 15.0 software. The average intra
      sinus bone gain with MP3 biomaterial of porcine origin was 4.13 +/- 0.97 SD mm at
      the moment of implant placement, 3.90 +/- 1.15 SD mm after twelve months, 3.74 +/
      1.05 SD mm after 24 months and 3.62 +/- 1.75 SD mm after 36 months. Two implants
      were lost at the moment of prosthesis placement. CONCLUSIONS: Alveolar lifting
      technique in the upper maxilla using bone dilators achieved a 96.6 % implant
      success rate after a three-year follow-up. Intra-sinus bone biomaterial
      remodeling was 0.51 +/- 0.08 mm from day zero to the thirty-six-month follow-up.
      This is a procedure that reduces the amount of surgery necessary and is of both
      aesthetic and functional benefit to the patient.

PMID- 20038920
TI  - High prevalence of human cytomegalovirus in a population of periodontally healthy
      subjects.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) appears to be more frequent in
      periodontally affected patients than in healthy control groups. Based on this
      assumption, it has been suggested that HCMV may play a role in the pathogenesis
      of periodontal disease. OBJECTIVE: The objective of this uncontrolled study was
      to assess the occurrence of HCMV in a large unselected population of
      periodontally healthy subjects. STUDY DESIGN: Fifty consecutive periodontally
      healthy patients satisfied the inclusion criteria. Two samples of gingival
      crevicular fluids were taken from two non-bleeding on probing sites for each
      patient. Samples were collected from the anterior and the posterior area.
      Polymerase chain reaction (PCR) was used to identify the presence of HCMV.
      RESULTS: HCMV was detected in 17 (33%) out of 50 participants. Ten subjects
      showed presence of HCMV on both anterior and posterior sites, whereas the
      remaining 7 only had HCMV present in the anterior sites. No differences were
      noticed between HCMV positive and HCMV negative in terms of smoking (p = 0.33),
      drinking habits (p=0,94) or the presence of prosthodontic restorations (p= 0,89).
      CONCLUSIONS: HCMV was detected in a high proportion of periodontally healthy
      subjects. Its presence was not found to be influenced by smoking or drinking
      habits.

PMID- 20038921
TI  - Why myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may kill you:
      disorders in the inflammatory and oxidative and nitrosative stress (IO&NS)
      pathways may explain cardiovascular disorders in ME/CFS.
AB  - There is evidence that disorders in inflammatory and oxidative and nitrosative
      (IO&NS) pathways and a lowered antioxidant status are important
      pathophysiological mechanisms underpinning myalgic encephalomyelitis / chronic
      fatigue syndrome (ME/CFS). Important precipitating and perpetuating factors for
      ME/CFS are (amongst others) bacterial and viral infections; bacterial
      translocation due to an increased gut permeability; and psychological stress.
      Recently, Jason et al (2006) reported that the mean age of patients with myalgic
      encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7
      years, is significantly lower than the age of those dying from heart failure in
      the general US population, i.e. 83.1 years. These findings implicate that ME/CFS
      is a risk factor to cardio-vascular disorder. This review demonstrates that
      disorders in various IO&NS pathways provide explanations for the earlier
      mortality due to cardiovascular disorders in ME/CFS. These pathways are: a)
      chronic low grade inflammation with extended production of nuclear factor kappa B
      and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS
      with increased peroxide levels, and phospholipid oxidation including oxidative
      damage to phosphatidylinositol; c) decreased levels of specific antioxidants,
      i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial
      translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared
      fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels;
      and f) the presence of viral and bacterial infections and psychological
      stressors. The mechanisms whereby each of these factors may contribute towards
      cardio-vascular disorder in ME/CFS are discussed. ME/CFS is a multisystemic
      metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase
      the risk for cardiovascular disorders.

PMID- 20038922
TI  - Value of amniotic fluid interleukin-8 for the prediction of histological
      chorioamnionitis in preterm premature rupture of membranes.
AB  - OBJECTIVE: To determine whether amniotic fluid levels of interleukin-8 (IL-8) are
      of value in the antenatal diagnosis of acute histological chorioamnionitis (HCA)
      in preterm premature rupture of membranes (PPROM). SETTING: Department of
      Obstetrics and Gynaecology, Charles University, Medical School and University
      Hradec Kralove, Czech Republic. METHODS: We compared amniotic fluid IL-8 levels
      in twenty-nine pregnant women with preterm premature rupture of membranes between
      24th and 36th gestational weeks with presence and absence acute histological
      chorioamnionitis or/and microbial invasion in the amniotic cavity using
      nonparametric tests (Mann-Whitney test), given the non-normal distribution of
      analyte. Comparisons of proportions were performed with Shapiro-Wilk normality
      test. RESULTS: Patients with HCA had a significantly higher median amniotic fluid
      IL-8 concentration than patients without the histological signs of
      chorioamnionitis (1867 pg/mL, 826-5577 versus 1045 pg/mL, 60-4133, p=0.013).
      Patients with MIAC had a significantly higher median amniotic fluid level than
      patients without invasion (1888 pg/mL, 519-5577 versus 1225 pg/mL, 60-2766, p=
      0.017). Women with HCA and MIAC had a significantly higher median amniotic fluid
      IL-8 level than women without histological signs of chorioamnionitis and
      microbial invasion (3117 pg/mL, 826-5577 versus 1468 pg/mL, 394-2766, p=0.034).
      CONCLUSIONS: HCA or/and MIAC are associated with a significant increase of
      amniotic fluid interleukin-8 levels. Amniotic fluid IL-8 seems to be a marker of
      intraamniotic inflammation.

PMID- 20038923
TI  - Significance of the plasma membrane for the nerve cell function, development and
      plasticity.
AB  - Lipoid character of plasma membrane namely the presence of polyenic fatty acids
      enables to interact with membrane proteins and in certain extent also to modulate
      their function. During the development, molecules of membrane fatty acids become
      more and more complex, and the ratio of polyenic fatty acids/saturated fatty
      acids in the brain rises, while the concentration of monoenic fatty acids
      remained relatively stable. This phenomenon is apparent also in the ratio of
      unsaturated fatty acids OMEGA-3 in plasma of newborns which correlates with the
      birth weight. Plasma membrane reflects local specializations of nerve cells. Its
      composition varies in functionally specialized regions called domains.
      Specialized domains of nerve cells determine the function of dendrites, soma,
      axon, axon hillock ect. Premature weaning of laboratory rats results in
      structural changes and in the increase of excitability of neuronal circuits in
      hypothalamus, septum and hippocampus which indicate the possibility of membrane
      composition changes. In synapses, transport proteins of synaptic vesicles, act
      together with the specific proteins of the presynaptic membrane. Membrane
      proteins determine the release of neurotransmitter at different conditions of
      synaptic activity, and they can contribute to the recovery of neurotransmitter
      content after the repeated hyperactivity. In the model of experimental kindling,
      repeated seizures bring about decreases and distribution changes of synaptic
      vesicles.

PMID- 20038925
TI  - REM sleep without atonia in narcolepsy.
AB  - OBJECTIVE: While there are a number of observations/quantifications indicating a
      greater proportion of REM sleep without atonia (RWA) in narcolepsy, the intra
      night distribution of this parameter has not been evaluated. MATERIALS AND
      METHODS: Thirty-four patients (15 men and 19 women; mean age 44.9 +/- 18.9) with
      narcolepsy-cataplexy were included in this retrospective study. The clinical
      diagnosis was confirmed by MSLT, video-polysomnography and HLA typing.
      Polysomnographic recordings were scored with particular regard to REM sleep
      without atonia (RWA) across all the nocturnal REM periods. RWA scoring was done
      according to a standard method. RESULTS: The analysis showed a significant
      increase in the proportion of REM sleep without atonia during successive
      nocturnal REM periods in narcoleptic patients (p<0.01). No correlation was found
      between the percentage of RWA and the severity or duration of the disease, no age
      effect was documented. CONCLUSION: The study demonstrates for the first time an
      increasing amount of RWA during the night suggesting enhanced nocturnal REM sleep
      motor disturbance.

PMID- 20038924
TI  - Self-harm in adolescence: a girl who swallowed needles.
AB  - Self-harm represents a serious and pathological behavior that occurs most notably
      during adolescent years and currently seems to be a problem that is on the
      increase. Self-harm is a self destructive behavior which most frequently takes
      the form of cutting and burning. Relative to suicidal behavior, self-harm, in and
      of itself, is not intended to be lethal and tends to be repeated and addictive.
      However, in cases of self-harm the risk of suicidal behavior cannot be ignored.
      This presentation is a case study of a girl who engaged in an unusual form of
      self-harm, by swallowing needles.

PMID- 20038926
TI  - Panic disorder and dissociation - comparison with healthy controls.
AB  - OBJECTIVE: According to recent findings, clinical symptoms of the patients
      suffering from panic disorder are related to dissociation. The aim of our study
      is to examine if the dissociation, can influence the intensity of psychopathology
      in patients suffering from panic disorder with or without agoraphobia and compare
      the levels of dissociation in the patients and healthy subjects. METHODS: 41
      patients suffering from panic disorder (70.1% females) and 66 healthy controls
      (77.3% females) were included in the study. The patients were psychiatrically
      assessed and the subjective intensity of symptoms was evaluated using Beck
      Anxiety Inventory and Beck Depression Inventory. All participants were assessed
      with the Dissociative Experiences Scale (DES). RESULTS: The two groups didn't
      differ in demographic variables like age, gender and education. Level of the
      psychological dissociation assessed with the DES was correlated with the severity
      of subjective anxiety symptoms (p<0.0001), but not with the severity of
      depression symptoms. Patients did not have significantly higher mean score on the
      DES than healthy controls. CONCLUSIONS: Our results suggest that the level of
      psychological dissociation in panic disorder patients is associated with the
      severity of anxiety but not depressive symptoms.

PMID- 20038927
TI  - Mild postnatal separation stress reduces repeated stress-induced
      immunosuppression in adult BALB/c mice.
AB  - OBJECTIVES: Different inbred mouse strains but also each animal of the same
      strain show an individually different stress response which is influenced by
      genetic and environmental factors such as early life experiences. In this study,
      we investigated consequences of mild postnatal stress exposure on the stress
      coping style of adult BALB/c mice. METHODS: We used a model of mild early life
      stress where neonatal mice were repeatedly separated from the dam staying with
      their siblings for 1-h each day during the first two postnatal weeks. The
      environment during maternal separation was adapted to the nest (bedding, 37
      degrees C warm). RESULTS: Adult female BALB/s mice that underwent the maternal
      separation protocol or were not isolated from the dam in early life were exposed
      to combined acoustic and restraint stress in adulthood. Repeated maternal
      separation which was performed under ambient conditions increased the stress
      coping ability of mice at the age of 12 weeks when exposed to this psychological
      stressors. By acoustic and restraint stress-induced alterations such as high
      corticosterone levels, an anti-inflammatory immune conditioning with an ex vivo
      hyperinducibility of interleukin-10 of splenocytes and a massive loss of body
      weight were significantly reduced in the maternally separated group compared with
      conventionally bred control mice. CONCLUSIONS: Mild maternal separation in early
      life modifies the stress coping style of adult female BALB/c mice to a more
      stress-resistant phenotype which shows reduced repeated stress-induced immune
      suppression and weight loss and is linked to reduced release of glucocorticoids
      after stress exposure.

PMID- 20038928
TI  - Maternal plasma cytokines concentrations and insulin resistance in first
      trimester in relation to fetal growth.
AB  - OBJECTIVE: Fetal growth is determined by genetic factors and placental supply.
      There is evidence that insulin might contribute to the up-regulation of placental
      transporter activity. The dysregulation of adiponectin and leptin is found in
      insulin resistance. The objective of this study was to evaluate the relation of
      maternal plasma cytokine and insulin concentrations in the first trimester of
      pregnancy to fetal growth. METHODS: 55 women with singleton pregnancy, between
      12th and 14th weeks of gestation, were included to the study. Plasma
      concentrations of adiponectin, leptin, insulin and glucose were analyzed together
      with fetal ultrasound measurements and neonatal birth weight. The HOMA-IR were
      calculated (fasting insulin (microU/ml) x fasting glucose (mmol/l/22.5) to assess
      the insulin sensitivity. RESULTS: Mean concentrations of adiponectin, leptin and
      insulin were 15.29 +/- 13.83 microg/ml, 6.93+/-5.39 ng/ml and 43.59+/-26.28,
      respectively. The average insulin resistance defined by HOMA-IR was 1.35+/-0.8.
      The ratios of adiponectin to leptin, adiponectin to insulin and HOMA-IR were
      calculated. The percentiles of fetal crown-rump length (CRL) were negatively
      correlated with adiponectin plasma concentration (r=-0.32; p<0.05), with no
      relation to leptin and insulin plasma concentration. Correlations between fetus
      CRL percentile and the ratio of adiponectin to leptin concentration (r=-0.37;
      p<0.02) and adiponectin to HOMA-IR (r=0.35; p<0.05) were also observed. No
      association between adiponectin, leptin, fasting insulin, HOMA-IR and neonatal
      birth weight or birth weight percentile was found. The percentile of fetal CRL in
      the 1st trimester was positively correlated with neonatal birth weight percentile
      (r=0.3; p<0.05). CONCLUSIONS: The results of this study imply that maternal
      adiponectin concentration may play a role in early determination of fetal growth.

PMID- 20038929
TI  - Lymphocytic hypophysitis with dacryoadenitis in a male patient: non-invasive
      diagnosis and high-dose methylprednisolone pulse therapy.
AB  - OBJECTIVE: Lymphocytic hypophysitis (LH) is a rare autoimmune disorder associated
      with lymphocytic cell infiltration of the pituitary. It is often detected in
      patients with other autoimmune systemic diseases such as Hashimoto's thyroiditis,
      epinephritis, megaloblastic anemia, and Langerhans cell histiocytosis. Pituitary
      biopsy and invasive histopathological examination provide the most reliable
      evidence for LH diagnosis. However, because glucocorticoids are extensively used
      for the treatment of disease, pathological diagnosis is not always necessary.
      Here, we report a rare case of a male patient (50 y) with LH associated with
      dacryoadenitis that was successfully treated with high-dose of
      methylprednisolone. RESULTS: The patient had a history of swollen lacrimal glands
      for two years. In addition, magnetic resonance imaging (MRI) showed a markedly
      thickened infundibular stem and an indiscernible signal in the posterior lobe of
      the pituitary. Biopsy of the lacrimal glands revealed reactive hyperplasia of the
      lymphoid tissue. After a high-dose of methylprednisolone pulse treatment (HDMPT),
      lacrimal gland swelling and infundibular stem thickness were reduced, and
      adenopituitary function improved within a short time period. CONCLUSIONS:
      Although association of LH with dacryoadenitis is a rare, it can be effectively
      managed with HDMPT. In addition, response to HDMPT can avoid the more invasive
      diagnostic procedures, including surgical intervention and pituitary biopsies.

PMID- 20038930
TI  - Professor Franz Halberg - the grand democrat in the global science. From the
      molecule to cosmos and back.

PMID- 20038931
TI  - Is combined treatment more effective than switching to monotherapy in patients
      with resistant depression? A retrospective study.
AB  - OBJECTIVE: The aim of this retrospective study was to compare the efficacy of
      combination therapy (combinations of antidepressants and various augmentations)
      and antidepressant monotherapy in the treatment of patients, who failed to
      respond at least to one previous antidepressant trial in the routine clinical
      practice. METHODS: We reviewed chart documents of patients hospitalized at Prague
      Psychiatric Center for depressive disorder from June 2005 to June 2007 and
      finished at least 4 weeks of new treatment. Depressive symptoms and overall
      clinical status were assessed using Montgomery and Asberg Depression Rating
      Scale, Clinical Global Impression and Beck Depression Inventory - Short Form at
      the baseline and in the end of treatment. RESULTS: We identified 49 inpatients
      (24-combined treatment, 25-monotherapy), who were suitable for analyses. Both
      groups were equal in baseline characteristics and in the duration of index
      episode treatment. The combined treatment was superior to the monotherapy switch
      in the MADRS median score reduction (16 vs. 9 points, p=0.01). The combined group
      achieved higher response rate compared to monotherapy group (67% vs. 36%,
      p=0.05). Number need to treat for response was 3.3 (95% CI, 1.85-37.3).
      CONCLUSION: The findings of this study suggest that combined treatment is more
      efficacious than switch to monotherapy in the treatment of resistant depression.

PMID- 20038932
TI  - Dissociative disorder and dissociation - comparison with healthy controls.
AB  - OBJECTIVE: The aim of our study is to examine if the dissociation, can influence
      intensity of psychopathology in patients suffering with dissociative disorders
      compare the level of dissociation of the patients with the data of healthy
      subjects. METHODS: 32 patients suffering with various types of dissociative
      disorder (9 males and 23 females) and 93 healthy controls (29 males and 64
      females) were included into the study. The patients were psychiatrically assessed
      and the subjective intensity of symptoms was evaluated by Beck Anxiety Inventory
      and Beck Depression Inventory. All participants were assessed with the
      Dissociative Experiences Scale (DES). RESULTS: The two groups didn't differ in
      demographic variables like age, gender and education. Level of the psychological
      dissociation assessed with the DES was correlated with the severity of subjective
      anxiety symptoms (p<0.0001), and with the severity of depression symptoms
      (p<0.0001). Patients had statistically significant higher mean score of DES than
      healthy controls (p<0.0001). CONCLUSIONS: Our results suggest that the level of
      psychological dissociation in dissociative disorder patients is associated with
      the severity of anxiety and depressive symptoms.

PMID- 20038933
TI  - COMT polymorphisms in impulsively violent offenders with antisocial personality
      disorder.
AB  - OBJECTIVE: The relationship between catechol-O-methyltransferase (COMT)
      polymorphisms and violent behaviour was tested in highly selected group of non
      psychotic violent offenders. METHODS: We conducted an association study comparing
      47 male repeatedly sentenced for impulsive violent attacks diagnosed with
      Antisocial Personality Disorder (APD) with 43 healthy male controls matched on
      education. Three COMT polymorphisms were analysed: COMT Val158Met and COMT
      Ala146Val on exon 4, and untranslated polymorphism on the 6th exon, at the
      regulatory region of the COMT gene with deletion-insertion character del/C.
      RESULTS: Logistic regression analysis revealed that while Val158Met is not
      associated with violence in APD, another COMT polymorphism - COMT Ala146Val is
      more frequent among violent offenders with APD (p=0.017). CONCLUSIONS: To
      conclude, our findings provide further support that COMT is a modifying gene that
      plays a role in determining interindividual variability in the proclivity for
      violent behaviour in subjects without major mental disorder.

PMID- 20038934
TI  - Can increased use of ART retrieve the Czech Republic from the low fertility trap?
AB  - OBJECTIVE: The aim of the study was to evaluate the importance of increased use
      of assisted reproduction technologies (ART) for the fertility trends in the Czech
      Republic. DATA AND METHODS: Comparative analysis based on demographic and ART
      data was used. Demographic data have been published by EUROSTAT and the Czech
      Statistical Office. ART data have collected by ESHRE. FINDINGS: In the 1990s a
      trend towards later childbearing contributed greatly to the decline in total
      fertility rate (TFR) in the Czech Republic. Recently, recuperation of delayed
      births has resulted in the increase of TFR to 1.5 children per woman which is
      considered to be a critical minimum level. The highest increase in fertility
      rates occurred in the age group of 35-39, in which the contribution of ART
      treatments usually is greatest. Moreover, a substantial increase of multiple
      births has been registered. In 2005 the estimated share of children born after
      ART in the Czech Republic (3%) was close to countries with the highest share
      (Nordic countries, Belgium or Slovenia). However, the Czech Republic registered
      only half the number of ART cycles per million inhabitants than in those
      countries. Contrary to Nordic countries the Czech Republic faced an extremely low
      TFR of 1.28 children per woman. As the estimation of average number of cycles
      suggests, the need for fertility treatment has not been met in the Czech Republic
      yet. Moreover, due to the continuous postponement of childbearing to higher women
      s age, demand for ART treatment will be even higher in the near future and will
      probably result in the need of more than 2 500 cycles per million inhabitants in
      the Czech Republic. CONCLUSIONS: Spreading of ART is particularly relevant in the
      countries caught in the low fertility trap as higher impact on fertility trends
      could be expected. In the Czech Republic there is a chance to get over the
      critical level of TFR if comprehensive population policy including the improved
      access to ART based on well-considered strategy with explicit aim to optimize the
      quality of health care was accepted. However, from the demographic perspective
      the risk of further delay of childbearing encouraged by ART treatment should be
      taken into account while making these decisions.

PMID- 20038935
TI  - Bilateral neurogenic hip arthropathy. A case report.
AB  - Neurogenic arthropathy is a rare joint disorder, characterized by rapid
      progression and marked destruction of articular surfaces (known as Charcot's
      joint) with only mild to moderate pain. Most cases are related to diabetic
      neuropathy, but they may complicate the course of other neurogenic clinical
      conditions such as neurosyphilis (tabes dorsalis), syringomyelia,
      myelomeningocele, Peroneal Muscular Atrophy, spine or peripheral nerve injury,
      alcoholism and avitaminosis. Loss of superficial sensation and proprioception
      plays a pivotal role in development of arthropathy because it affects the joint's
      normal protective reflexes and leads to joint instability, degeneration and
      destruction. The authors describe an unusual case of bilateral neurogenic hip
      arthropathy in a 61-year old women who developed this condition in the course of
      multilevel lumbar spondylosis with spinal and nerve root compression. The patient
      underwent a successful bilateral hip replacement and remains almost asymptomatic
      contrary to literature reports that suggest high risk of complications after the
      operative treatment of Charcot's joints.

PMID- 20038936
TI  - Alcohol use and discounting of delayed and probabilistic gain and loss.
AB  - OBJECTIVE: Little is known about the relationship between alcohol and discounting
      of loss, one of procrastinative behaviors. This study examined the relationship
      between the frequency of alcohol use and discounting delayed and probabilistic
      gain and loss, which is of interest in neuroeconomics of addiction. METHODS:
      Thirty-three subjects conducted tasks of delay and probability discounting of
      gain and loss. Their alcohol use was also assessed. RESULTS: The frequency of
      alcohol use was significantly correlated with the degree to which delayed
      monetary losses were discounted. CONCLUSIONS: Frequent use of alcohol may
      associate with an increased degree of procrastination. Further, the degrees of
      delay discounting of loss could be a predictor of a frequent alcohol intake.

PMID- 20038937
TI  - Engineering cell-permeable protein.
AB  - The protein transduction technique enables the direct delivery of biologically
      active material into mammalian cells [for review see (1,2)]. For this one can
      make use of the translocating ability of so-called cell penetrating peptides
      (CPPs), also designated as protein transduction domains (PTDs). The TAT-CPP
      derived from the human immunodeficiency virus type 1 (HIV-1) Tat (trans-activator
      of transcription) protein has been widely used. The positively charged TAT
      promotes cell permeability thereby overcoming the barriers of the cellular
      membrane by endocytosis or/and direct membrane penetration(2). In combination
      with a nuclear localization signal (NLS) fusion proteins are able to enter the
      nucleus exhibiting functionality. Our video presentation demonstrates, as an
      exemplification for the engineering of cell-permeable proteins, the construction,
      production and application of a cell-permeable version of the DNA-modifying
      enzyme Cre. Cre is a site-specific recombinase that is able to recognize and
      recombine 34 base pair loxP sites in mammalian cells in vitro and in vivo.
      Therefore the Cre/loxP system is widely used to conditionally induce mutations in
      the genome of living cells(3,4). The delivery of active Cre recombinase to cells,
      however, represents a limitation. We describe the pSESAME vector system, which
      allows a direct insertion of the gene-of-interest and provides a platform to
      rapidly clone different domains and tags used within the vector in a convenient
      and standardized manner. Rearranging of the different tags has been shown to
      modify the biochemical properties of the fusion proteins providing a possibility
      to achieve higher yield and better solubility. We demonstrate how to express and
      purify recombinant cell-permeant proteins in and from E. coli. The functionality
      of the recombinant Cre protein is finally validated in cell culture by assessing
      its intracellular recombinase activity.

PMID- 20038938
TI  - Cord clamping and neurodevelopmental outcome in very low birth weight infants.

PMID- 20038939
TI  - Identity theft in the delivery room.

PMID- 20038940
TI  - A newborn with infantile fibrosarcoma of foot: treatment with chemotherapy and
      extremity-sparing surgery.
AB  - Infantile fibrosarcoma represents less than 1% of all childhood cancers, but it
      is the most common soft-tissue sarcoma in those under 1 year of age. We report an
      infant with congenital infantile fibrosarcoma diagnosed as hemangiopericytoma. He
      was treated with chemotherapy and extremity-sparing surgery. Amputation was
      avoided.

PMID- 20038941
TI  - Perinatal management of harlequin ichthyosis: a case report and literature
      review.
AB  - Harlequin ichthyosis (HI) is a rare and severe form of congenital ichthyosis.
      Linked to deletion and truncation mutations of a keratinocyte lipid transporter,
      HI is characterized by diffuse epidermal hyperkeratinization and defective
      desquamation. At birth, the HI phenotype is striking with thick hyperkeratotic
      plate-like scales with deep dermal fissures, severe ectropion and eclabium, among
      other findings. Over the first months of life, the hyperkeratotic covering is
      shed, revealing a diffusely erythematous, scaly epidermis, which persists for the
      remainder of the patient's life. Although HI infants have historically succumbed
      in the perinatal period related to their profound epidermal compromise, the
      prognosis of HI infants has vastly improved over the past 20 years. Here, we
      report a case of HI treated with acitretin, focusing on the multi-faceted
      management of the disease in the inpatient setting. A review of the literature of
      the management of HI during the perinatal period is also presented.

PMID- 20038942
TI  - Fanconi's anemia, type A presenting as VACTERL association with atresia right
      external auditory canal.

PMID- 20038944
TI  - What editors want in an abstract.

PMID- 20038945
TI  - Attacking the source: anti-PDX-1 responses in type 1 diabetes.
AB  - Type 1 diabetes (T1D) develops as a consequence of abnormal responses against
      several self-antigens, eventually leading to the autoimmune attack and
      destruction of the insulin-producing beta cells in the pancreas. In this issue of
      Laboratory Investigation, Li et al propose the transcription factor Pancreatic
      and duodenal homeobox 1 (PDX-1) as a T1D autoantigen by demonstrating
      autoreactivity to this pancreas-specific protein in both the NOD mouse model and
      patients with T1D. Because of the known roles of PDX-1 in pancreatic development
      as well as beta cell maintenance and function, targeting of PDX-1 expressing
      cells may result in the elimination of not only beta cells but also the
      progenitor cells required for regeneration of insulin-producing cells.

PMID- 20038946
TI  - Altered arachidonic acid cascade enzymes in postmortem brain from bipolar
      disorder patients.
AB  - Mood stabilizers that are approved for treating bipolar disorder (BD), when given
      chronically to rats, decrease expression of markers of the brain arachidonic
      metabolic cascade, and reduce excitotoxicity and neuroinflammation-induced
      upregulation of these markers. These observations, plus evidence for
      neuroinflammation and excitotoxicity in BD, suggest that arachidonic acid (AA)
      cascade markers are upregulated in the BD brain. To test this hypothesis, these
      markers were measured in postmortem frontal cortex from 10 BD patients and 10 age
      matched controls. Mean protein and mRNA levels of AA-selective cytosolic
      phospholipase A(2) (cPLA(2)) IVA, secretory sPLA(2) IIA, cyclooxygenase (COX)-2
      and membrane prostaglandin E synthase (mPGES) were significantly elevated in the
      BD cortex. Levels of COX-1 and cytosolic PGES (cPGES) were significantly reduced
      relative to controls, whereas Ca(2+)-independent iPLA(2)VIA, 5-, 12-, and 15
      lipoxygenase, thromboxane synthase and cytochrome p450 epoxygenase protein and
      mRNA levels were not significantly different. These results confirm that the
      brain AA cascade is disturbed in BD, and that certain enzymes associated with AA
      release from membrane phospholipid and with its downstream metabolism are
      upregulated. As mood stabilizers downregulate many of these brain enzymes in
      animal models, their clinical efficacy may depend on suppressing a pathologically
      upregulated cascade in BD. An upregulated cascade should be considered as a
      target for drug development and for neuroimaging in BD.

PMID- 20038947
TI  - Novel loci for major depression identified by genome-wide association study of
      Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three
      studies.
AB  - We report a genome-wide association study (GWAS) of major depressive disorder
      (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve
      Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for
      association was detected. We also carried out a meta-analysis of three European
      ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression
      and the publicly available Genetic Association Information Network-MDD data set.
      These data sets, totaling 3957 cases and 3428 controls, were genotyped using four
      different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of
      2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped
      data where available and imputed data otherwise, single-SNP association tests
      were carried out in each sample with correction for ancestry-informative
      principal components. The strongest evidence for association in the meta-analysis
      was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10-7), SP4 (P=7.68 x 10-7)
      and GRM7 (P=1.11 x 10-6). Additional exploratory analyses were carried out for a
      narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and
      separately for males and females. Several of the best findings were supported
      primarily by evidence from narrow cases or from either males or females. On the
      basis of previous biological evidence, we consider GRM7 a strong MDD candidate
      gene. Larger samples will be required to determine whether any common SNPs are
      significantly associated with MDD.

PMID- 20038948
TI  - A genome-wide survey of human short-term memory.
AB  - Recent advances in the development of high-throughput genotyping platforms allow
      for the unbiased identification of genes and genomic sequences related to
      heritable traits. In this study, we analyzed human short-term memory, which
      refers to the ability to remember information over a brief period of time and
      which has been found disturbed in many neuropsychiatric conditions, including
      schizophrenia and depression. We performed a genome-wide survey at 909 622
      polymorphic loci and report six genetic variations significantly associated with
      human short-term memory performance after genome-wide correction for multiple
      comparisons. A polymorphism within SCN1A (encoding the alpha subunit of the type
      I voltage-gated sodium channel) was replicated in three independent populations
      of 1699 individuals. Functional magnetic resonance imaging during an n-back
      working memory task detected SCN1A allele-dependent activation differences in
      brain regions typically involved in working memory processes. These results
      suggest an important role for SCN1A in human short-term memory.

PMID- 20038949
TI  - A red-shifted Renilla luciferase for transient reporter-gene expression.

PMID- 20038950
TI  - Restricted ethnic diversity in human embryonic stem cell lines.

PMID- 20038952
TI  - Induced pluripotent stem cell technology for the study of human disease.

PMID- 20038951
TI  - The mysteries of induced pluripotency: where will they lead?

PMID- 20038953
TI  - Stem cell research policy and iPS cells.

PMID- 20038954
TI  - Reduce, reuse, reprogram.

PMID- 20038955
TI  - Sorting cardiomyocytes: a simple solution after all?

PMID- 20038957
TI  - A pharmacogenetic study of docetaxel and thalidomide in patients with castration
      resistant prostate cancer using the DMET genotyping platform.
AB  - The anticancer agent docetaxel shows significant inter-individual variation in
      its pharmacokinetic and toxicity profile. Thalidomide is an active anticancer
      agent and also shows wide pharmacological variation. Past pharmacogenetic
      research has not explained this variation. Patients with prostate cancer enrolled
      in a randomized phase II trial using docetaxel and thalidomide versus docetaxel
      alone were genotyped using the Affymetrix DMET 1.0 platform, which tests for 1256
      genetic variations in 170 drug disposition genes. Genetic polymorphisms were
      analyzed for associations with clinical response and toxicity. In all, 10 single
      nucleotide polymorphisms (SNPs) in three genes were potentially associated with
      response to therapy: peroxisome proliferator-activated receptor-delta (PPAR
      delta), sulfotransferase family, cytosolic, 1C, member 2 (SULT1C2) and
      carbohydrate (chondroitin 6) sulfotransferase 3 (CHST3). In addition, 11 SNPs in
      eight genes were associated with toxicities to treatment: spastic paraplegia 7
      (pure and complicated autosomal recessive) (SPG7), CHST3, cytochrome P450, family
      2, subfamily D, polypeptide 6 (CYP2D6), N-acetyltransferase 2 (arylamine N
      acetyltransferase) (NAT2), ATP-binding cassette, sub-family C (CFTR/MRP), member
      6 (ABCC6), ATPase, Cu++ transporting, alpha polypeptide (ATP7A), cytochrome P450,
      family 4, subfamily B, polypeptide 1 (CYP4B1) and solute carrier family 10
      (sodium/bile acid cotransporter family), member 2 (SLC10A2). Genotyping results
      between drug metabolizing enzymes and transporters (DMET) and direct sequencing
      showed >96% of concordance. These findings highlight the role that non-CYP450
      metabolizing enzymes and transporters may have in the pharmacology of docetaxel
      and thalidomide.

PMID- 20038959
TI  - Carbonic anhydrase IX expression in prostate cancer.
AB  - Tumour hypoxia is associated with over 70% of solid tumours including prostate
      and colorectal cancer. Hypoxia promotes tumour progression and resistance to
      treatment. Carbonic anhydrase IX (CA IX) is an endogenous marker of hypoxia. It
      is expressed in lung and renal cell carcinomas and is associated with a poor
      prognosis. CA IX has an important role in maintaining pH levels in the highly
      metabolically active cancer cell. The expression of CA IX in prostate cancer has
      not previously been investigated. Immunohistochemistry was used to examine CA IX
      expression in 59 patients, using tissue microarrays (TMAs) and full sections of
      BPH, surrounding stroma and prostate adenocarcinoma. Cores reviewed included 189
      BPH, 130 Gleason grade 3, 93 Gleason grade 4, 40 Gleason grade 5. CA IX
      expression in colorectal cancer and HIF 1alpha in prostate cancer acted as
      positive controls. There was only occasional cell staining for CA IX expression.
      Although prostate cancer is a hypoxic tumour it does not express CA IX. This
      implies it relies on alternative pathways for maintaining pH balance in cancer.
      These studies would indicate that CA IX is not a suitable marker of hypoxia in
      prostate cancer.

PMID- 20038958
TI  - Cyclooxygenases-1 and -2 differentially modulate leukocyte recruitment into the
      inflamed brain.
AB  - Peripheral leukocyte recruitment in neuroinflammatory conditions can exacerbate
      brain tissue damage by releasing cytotoxic mediators and by increasing vascular
      permeability. Cyclooxygenase (COX)-derived prostaglandins promote the migration
      of several immune cells in vitro, however, the specific roles of COX-1 and -2 on
      leukocyte recruitment in vivo have not been investigated. To examine the specific
      effects of COX-1 or COX-2 deficiency on neuroinflammation-induced leukocyte
      infiltration, we used a model of intracerebroventricular lipopolysaccharide (LPS)
      induced neuroinflammation in COX-1(-/-), COX-2(-/-), and their respective wild
      type (WT) ((+/+)) mice. After LPS, leukocyte infiltration and inflammatory
      response were attenuated in COX-1(-/-) and increased in COX-2(-/-) mice, compared
      with their respective WT controls. This influx of leukocytes was accompanied by a
      marked disruption of blood-brain barrier and differential expression of
      chemokines. These results indicate that COX-1 and COX-2 deletion differentially
      modulate leukocyte recruitment during neuroinflammation, and suggest that
      inhibition of COX-1 activity is beneficial, whereas COX-2 inhibition is
      detrimental, during a primary neuroinflammatory response.

PMID- 20038960
TI  - Time course of late rectal toxicity after radiation therapy for prostate cancer.
AB  - Rectum and bladder are the crucial organs at risk for curative radiation therapy
      of localized prostate cancer. We analyzed the incidence, profile and time course
      of late rectal radiation toxicity. A total of 320 patients with T1-3 prostate
      cancer were treated with three-dimensional conformal radiation therapy (3D-CRT).
      The prescription dose was 70 Gy for T1 and T2 patients (n=230) and 74 Gy for
      patients with locally advanced T3 tumors (n=90). Late rectal toxicity was graded
      according to the Fox Chase modification of the Radiation Therapy Oncology Group
      (RTOG) and Late Effects Normal Tissue Task Force (LENT) criteria. The median
      follow-up time was 6.2 years (range 0.2-10.7 years). At 5 years, the risk for the
      development of grade 2 and 3 rectal toxicities was 15.6 and 7.0%, respectively.
      All new cases of grade 2 and 3 rectal toxicities were observed within 5 years
      after treatment. Prevalence of grade 2 and 3 rectal symptoms showed fluctuation
      with maximum at 1.5 years and the minor peak at 4.5 years. Toxicity profile
      changed significantly over time. The proportion of rectal bleeding within grade 2
      and 3 toxicity decreased from 85% at 1.5 years to 46% at 4.5 years. Conversely,
      the proportion of fecal incontinence among grade 2 and 3 rectal symptoms
      gradually increased (0% at 1.5 years vs 27% at 4.5 years). Late rectal radiation
      toxicity represents a dynamic process. Rectal bleeding decreases and fecal
      incontinence increases over time.

PMID- 20038961
TI  - The AGL6-like gene OsMADS6 regulates floral organ and meristem identities in
      rice.
AB  - Although AGAMOUS-LIKE6 (AGL6) MADS-box genes are ancient with wide distributions
      in gymnosperms and angiosperms, their functions remain poorly understood. Here,
      we show the biological role of the AGL6-like gene, OsMADS6, in specifying floral
      organ and meristem identities in rice (Oryza sativa L.). OsMADS6 was strongly
      expressed in the floral meristem at early stages. Subsequently, OsMADS6
      transcripts were mainly detectable in paleas, lodicules, carpels and the
      integument of ovule, as well as in the receptacle. Compared to wild type plants,
      osmads6 mutants displayed altered palea identity, extra glume-like or mosaic
      organs, abnormal carpel development and loss of floral meristem determinacy.
      Strikingly, mutation of a SEPALLATA (SEP)-like gene, OsMADS1 (LHS1), enhanced the
      defect of osmads6 flowers, and no inner floral organs or glume-like structures
      were observed in whorls 2 and 3 of osmads1-z osmads6-1 flowers. Furthermore, the
      osmads1-z osmads6-1 double mutants developed severely indeterminate floral
      meristems. Our finding, therefore, suggests that the ancient OsMADS6 gene is able
      to specify "floral state" by determining floral organ and meristem identities in
      monocot crop rice together with OsMADS1.

PMID- 20038962
TI  - [Assessment of the new CKD-EPI equation to estimate the glomerular filtration
      rate].
AB  - INTRODUCTION: A recent report by the CKD-EPI Chronic Kidney Disease Epidemiology
      Collaboration) group describes a new equation to estimate the glomerular
      filtration rate (GFR). This equation has been developed from a population of
      8,254 subjects who had the GFR measured by iothalamate clearance (mean 68
      mL/min/1.73 m2, SD 40 mL/min/1.73 m2). It includes variables such as serum
      creatinine, age, sex and race with different formula according to race, sex and
      creatinine value. The CKD-EPI equation improved the accuracy and precision
      results of the current first-choice MDRD-IDMS (Modification of Diet in Renal
      Disease-Isotopic Dilution Mass Spectrometry) formula, specially for GFR > 60
      mL/min/1.73 m2 in a group of 3,896 subjects. METHODS: The goal of our study was
      to compare the estimated GFR by using the new equation CKD-EPI with MDRD-IDMS in
      a wide cohort of 14,427 patients (5,234 women and 9,193 men), and to analyze the
      impact of the new CKD-EPI formula on the staging of patients with CKD. RESULTS:
      Mean estimated GFR was 0.6 mL/min/1.73 m2 higher with CKD-EPI as compared to MDRD
      IDMS for the whole group, 1.9 mL/min/1.73 m2 higher for women and 0.2 mL/min/1.73
      m2 lower for men. The percentage of CKD staging concordancy between equations
      varied from 79.4 % for stage 3A and 98.6% for stage 5. For those patients younger
      than 70 years, 18.9 % and 24 % MDRD-IDMS stages 3B and 3A were reclassified as
      CKD 3A and 2 by CKD-EPI, respectively. For the same stages in the group younger
      than 70 years, the percentage of reclassified patients increased up to 34.4% and
      33.4%, respectively. CONCLUSION: The new CKD-EPI equation to estimate the GFR
      reclassifies an important number of patients to higher CKD stages (higher GFR),
      specially younger women, classified as CKD stage 3 by MDRD-IDMS.

PMID- 20038963
TI  - [Would prescription of erythropoiesis-stimulating agents in pre-dialysis change
      after results from TREAT study?].

PMID- 20038964
TI  - [Anaemia correction in diabetic patients with chronic kidney disease without
      substitutive treatment: teachings from TREAT study].

PMID- 20038965
TI  - [Feminisation and nephrology].
AB  - Feminisation in nephrology is very high and their consequence in clinical
      research appears as an interesting focus. Nephrologist women participate to
      working groups and research projects of the "Sociedad Espanola de Nefrologia" in
      similar percentage than they contribute to society, more or less 40 %.
      Nephrologist women are half of medicine PhD. However, nephrologists women are
      represented the fifth part in advanced projects within clinical research. If the
      nephrology is a speciality which will be able to keep up with the increasing of
      the assistance demand, the participation of the women in the clinical research is
      basic. Without looking down on the other topics, the clinical research within
      epidemiology and quality about the renal health could be particularly attractive
      for the women in nephrology.

PMID- 20038966
TI  - [Does Stewart-Fencl improve the evaluation of acid-base status in stable patients
      on hemodiafiltration?].
AB  - INTRODUCTION: The traditional evaluation of acid-base status relies on the
      Henderson-Hasselbach equation. In 1983, an alternative approach, based on
      physical and chemical principles was proposed by P. Stewart. In this approach,
      plasma pH is determined by 3 independent variables: pCO2, Strong Ion Difference
      (SIDm), which is the difference between the strong cations (Na +, K +, Ca ++, Mg
      ++) and the strong anions (Cl-, lactate) and total plasma concentration of
      nonvolatile weak acids (ATot), mainly inorganic phosphate and albumin.
      Bicarbonate is considered a dependent variable. The aim of this study was to
      evaluate the acid-base status using both perspectives, physical chemical and
      traditional approach. MATERIAL AND METHODS: We studied 35 patients (24 M; 11F) on
      hemodiafiltration, mean age was 67,2+/-15,7, 8+/-19,2 kg. We analyzed plasma
      chemistry including pH, pCO2, HCO3-, base excess and Na+, K+, Cl-, Ca++, Mg++,
      lactate and SIDm. The SID estimated (SIDe) was calculated by Figge's formula
      (1000 x 2.46E-11 x pCO2 / (10-pH) + Album gr/dl x (0.123 x pH-0.631) + P in
      mmol/l x (0.309 x pH-0.469) and Gap of the SID as the difference SIDm-SIDe.
      RESULTS: pH preHD was 7,36+/-0,08 and pH posHD 7,44+/-0,08 (p < 0.001). There was
      no significant differences between pCO2 pre and pos-HD. HCO3 - and base excess
      increased during the session (p < 0.001). SIDm decreased from 46,2+/-2,9 preHD to
      45+/-2,3 mEq/l postHD (p < 0.05). On the opposite, SIDe increased from 38,5+/-3,8
      to 42,9+/-3,1 mEq/l (p < 0.001). The Gap Anion descended from 18,6+/-3,8 preHD to
      12,8+/-2,8 mEq/l mEq/l postHD (p < 0.001) and the Gap of the SID 7,6+/-3 to 2,1+/
      2 (p < 0.001). Anion Gap correlated with the Gap-SID so much pre-HDF as pos-HDF.
      Delta Base excess correlated only with Delta of the Gap SID. CONCLUSION: Stewart
      Fencl's approach does not improve characterization of acid-base status in
      patients on chronic HDF. In presence of normocloremia the SIDm does not reflect
      the alkalinizing process of the session of hemodialysis. According this approach,
      hemodialysis therapy can be viewed as a withdrawal of inorganic anions,
      especially the sulphate. These anions are replaced by OH - and secondarily for
      HCO3-. The approach only improves the evaluation of unmeasured anions by the Gap
      of the SID, without the effect of albumin and phosphate.

PMID- 20038967
TI  - Prevalence of chronic renal disease in Spain: results of the EPIRCE study.
AB  - INTRODUCTION: Chronic kidney disease (CKD) is an independent cardiovascular risk
      factor. The knowledge of prevalence in general population may help to early
      detection of CKD and prevent or delay its progression. METHODS: Sociodemographic,
      baseline characteristics, and CKD prevalence (measured by centralized serum
      creatinine and MDRD equation) were evaluated in a randomly selected sample of
      general population aged 20 years or older, collected in all Spanish regions and
      stratified by habitat, age and sex according to 2001 census (n=2746). Univariate
      and multivariate logistic regression analyses were used to evaluate associations
      with CKD risk factors. RESULTS: Mean age was 49.5 years. The overall prevalence
      of Kidney Disease Outcomes Quality Initiative grades 3-5 CKD was 6.8%, with a 95%
      confidence interval (CI) of 5.4 to 8.2 (3.3% for age 40-64 years and 21.4% for
      age > 64 years). The prevalence estimates of CKD stages were: 0.99% for stage 1
      (glomerular filtration rate [GFR] >or=90 ml/min per 1.73 m2 with proteinuria);
      1.3% for stage 2 (GFR 60-89); 5.4% for stage 3a (GFR 45-59); 1.1% for stage 3b
      (GFR 30-44); 0.27% for stage 4 (GFR 15-29); and 0.03% for stage 5 (GFR < 15). An
      important prevalence of classical cardiovascular risk factors was observed:
      dyslipemia (29.3%), obesity (26.1%), hypertension (24.1%), diabetes (9.2%) and
      current smoking (25.5%). The independent predictor factors for CKD were age,
      obesity and previously diagnosed hypertension. CONCLUSION: The prevalence of CKD
      at any stage in general population from Spain is relatively high, especially in
      the elderly, and similar to countries of the same geographical area.
      Independently of age, two modifiable risks factors, hypertension and obesity, are
      associated with an increased prevalence of CKD.

PMID- 20038968
TI  - [Outcome implications of chronic kidney disease in the elderly].
AB  - Chronic kidney disease is considered to be a problem of public health problem
      from the application of Guidelines KDOQI/NKF. Majority patients diagnosed of
      chronic kidney disease are elderly. In these patients progression of renal
      disease is slow, being the mortality high to development of renal failure that
      needs dialysis. The current guidelines must apply with caution in these elders.

PMID- 20038969
TI  - [ABO-incompatible living-donor kidney transplantation].

PMID- 20038970
TI  - [ABO incompatible living donor kidney transplantation: a dream come true.
      Experience of Hospital Clinic of Barcelona].
AB  - INTRODUCTION: During the last years the number of patients on waiting list for
      kidney transplantation has been stable. Living donor kidney transplantation is
      nowadays a chance to increase the pool of donors. However, there are a group of
      patients with ABO incompatibility, making impossible the transplant until now.
      The aim of the present study is to describe the experience of Hospital Clinic
      Barcelona on ABO incompatible living transplantation. METHODS: A retrospective-
      descriptive study was made based on 11 living donor kidney recipients with ABO
      incompatibility in Hospital Clinic of Barcelona from October'06 to January'09.
      Selective blood group, antibody removal with specific immunoadsortion,
      immunoglobulin and anti- CD 20 antibody were made until the immunoglobulin (IgG)
      and isoaglutinine (IgM) antibody titters were 1/8 or lower. Immunosuppressive
      protocol was adjusted to particular recipient characteristics. Isoaglutinine
      titters were set before, during and post desensitization treatment and two weeks
      after transplant. Immunological, medical and surgical evaluation was the standard
      in living donor kidney transplant program. RESULTS: Medium age of donors and
      recipients were 47.8 +/- 12.4 and 44.4 +/- 14.1 years, respectively. 90% of
      donors were females and 73% of recipients males. Follow-up time was 10.2 +/- 10.2
      months. Siblings and spouses were the most frequent relation (n=4, 36.4%,
      respectively). Chronic glomerulonephritis, adult polycystic kidney disease and
      Alport syndrome, the most frequent cause of end-stage renal disease. All the
      patients acquire appropriate isoaglutinine titters pre transplant (< 1/8),
      requiring 5.54 +/- 2.6 immunoadsorption sessions pretransplant and 2.82
      posttransplant. One patient didn t need any immunoadsorption session
      (incompatibility blood group B) and another patient plasma exchange instead of
      immunoadsorption for being hypersensitized with positive flow cytometry
      crossmatch. Posttransplant isoaglutinine titters remained low. Two patients had
      cellular acute rejection episode (type IA and IB of Banff classification) with
      good response to corticosteroid treatment. Patient and graft survival were 91% at
      first year and remain stable during the follow-up. A graft lost by death of
      patient in relation to haemorrhagic shock developed within the first 72 hours
      after transplantation. Renal graft function at first year was excellent with
      serum creatinine of 1.3 +/- 0.8 mg/dl, creatinine clearance of 62.6 ml/min/1.73
      m2 and proteinuria of 244.9 mg/U-24h. CONCLUSION: ABO incompatible living donor
      kidney transplantation represent an effective and safe alternative in certain
      patients on waiting list for renal transplant, obtaining excellent results in
      patient and graft survival, with good renal graft function.

PMID- 20038971
TI  - [Design of a quality of life questionnaire in Spanish for children with chronic
      kidney disease].
AB  - Treatment of chronic kidney disease in childhood must include assessment of
      social and psychological aspects involved in the perceived quality of life of the
      child and its family. Our objective has been to design a specific tool in Spanish
      for measuring quality of life in pediatric patients with chronic kidney disease,
      since there is not a validated test for children at the moment. RESULTS: We
      designed a specific questionnaire for kidney disease in children based on the
      test of quality of life for adults with kidney disease (KDQOL-SFTM) and on the
      test of quality of life for children with epilepsy (CAVE) adapting them to
      children with kidney disease, denominating TECAVNER (Test of Quality of Life in
      Children with Kidney Disease). Reliability of this questionnaire determined be
      alfa Cronbach coefficient was 0,92. LIMITATIONS: Questionnaire determined by Test
      retest reliability and construct validity were not conducted. In conclusion, this
      is a first approach for design a specific health related quality of life test in
      Spanish for children with chronic kidney disease.

PMID- 20038972
TI  - [Perceived quality of life in children with chronic renal disease and in their
      parents].
AB  - INTRODUCTION: Chronic renal disease (CRD) affects physical, emotional and social
      wellbeing of children. Renal adult and adolescent patients have a poorer quality
      of life (QL) than healthy population but few studies have been performed in
      children with CRD and appropriate QL measurement tools. OBJECTIVES: To assess QL
      in children with CRD comparing it with healthy children. MATERIAL AND METHODS:
      Cross-sectional study in 71 children with CRD and 57 healthy children with the
      generic health status tool MOSF-SF-20 answered by children older than 9 and their
      parents and only by parents when children were younger than 9. RESULTS: Children
      with CRD have a poorer QL than healthy children with significant differences in
      general self-esteem, physical performance and physical activity and no
      significant difference in socialization. On the contrary they refer less pain and
      emotional discomfort than healthy population. Perceived QL of children by parents
      is also worse in CRD population affecting all but pain dominions. 9-12 years old
      children and their parents agree in all QL dominions while parents underestimate
      social function and emotional well-being when their children were older than 12.
      CONCLUSIONS: QL in children with CRD is worse than in healthy children mainly in
      physical function and general self-esteem and agree with parents perceptions.

PMID- 20038973
TI  - [Correlates of potassium transport during peritoneal equilibration tests using
      different dialysate glucose concentrations].
AB  - BACKGROUND: there are gaps in the knowledge of factors which influence peritoneal
      potassium transport in Peritoneal Dialysis (PD). The aims of this study were to
      compare peritoneal potassium transport in PD patients undergoing 2.27% and 3.86%
      peritoneal equilibration tests (PET), and to disclose clinical correlates of this
      phenomenon. METHOD: ninety PD patients underwent 2.27% and 3.86% PET, in a random
      order. We compared peritoneal potassium transport in both tests, and searched for
      correlations between D/P potassium at 240 minutes (main study variable) and PET
      derived markers of peritoneal function and selected demographic, clinical and
      biochemical variables, using a multivariate approach. MAIN RESULTS: D/P potassium
      showed a good agreement between both PET, and presented a univariate association
      with creatinine transport, but not with plasma potassium, ultrafiltration or
      sodium dip. Age, PD modality, peritoneal glucose load, icodextrin, ACEI-ARA and
      calcium antagonist therapy, urinary potassium and glomerular filtration rate were
      other univariate correlates of potassium transport. Multivariate analysis
      confirmed D/P creatinine at 240 minutes (B=0.40 [95% CI 0.26-0.53] 2.27%, B=0.36
      [0.21-0.51] 3.86%, p < 0.0005) as the main predictor of D/P potassium at 240
      minutes. Urinary potassium, rather than glomerular filtration rate, sustained
      also an inverse correlation with the dependent variable. Treatment with ACEI-ARA
      was consistently associated with peritoneal potassium transport (3.86% PET B=0.08
      [0.04-0.12], p < 0.0005). CONCLUSIONS: The 2.27% and the 3.86% PET show a good
      agreement at the time of estimating peritoneal potassium transport. Urinary
      potassium excretion and treatment with ACEI-ARA (3.86% test) show an independent
      association with peritoneal potassium transport rates.

PMID- 20038974
TI  - Acute lupus hemophagocytic syndrome: report of a case.
AB  - Hemophagocytic Syndrome is a clinical condition characterized by the activation
      of either macrophages or histiocytes with a prominent hemophagocytosis feature in
      the bone marrow and other reticuloendothelial systems. It leads to the
      phagocytosis of erythrocytes, leukocytes, platelets and their precursors. The
      presence of hemophagocytosis can be associated to infections, malignancies,
      autoimmune diseases, drugs and a variety of other medical conditions. We report a
      case of a previously healthy 36 year-old woman that developed hemophagocytosis at
      the same time that fulfilled diagnostic criteria for systemic lupus
      erythematosus. Lupus related hemophagocytic syndrome is a rare and potentially
      fatal entity. It offers significant differential diagnosis challenges and
      requires urgent therapeutic intervention. There are only few cases reported in
      the literature. However, much is still needed in order to better understand its
      causes, all the immunopathogenic mechanisms, as well as its clinical and
      therapeutic aspects.

PMID- 20038975
TI  - Dopamine receptor loss of function is not protective of rd1 rod photoreceptors in
      vivo.
AB  - PURPOSE: The retinal degeneration (rd1) mouse undergoes a rapid loss of rod
      photoreceptors due to a defect in the cGMP-phosphodiesterase gene. We have
      previously demonstrated that dopamine (DA) antagonists or DA depletion blocks
      photoreceptor degeneration and that DA is necessary for photoreceptor
      degeneration in the rd1 mouse retinal organ culture model. Antagonists for either
      D1- or D2-family DA receptors are protective in rd1 organ cultures. METHODS: To
      determine whether photoreceptor survival can be increased in vivo in the rd1
      mouse, we used both a pharmacological and a genetic approach. The pharmacological
      approach involved three techniques to administer 6-hydroxydopamine (6-OHDA) in an
      attempt to deplete DA in postnatal mouse retina in vivo. As a genetic
      alternative, DA receptor signaling was inactivated by crossbreeding rd1 mice to
      D1, D2, D4, and D5 knockout mice to create four lines of double mutants. RESULTS:
      Pharmacological DA depletion was incomplete due to the limiting size of the
      postnatal mouse eye and the lethality of systemic inhibition of DA signaling. In
      all four lines of double mutants, no increase in rod photoreceptor survival was
      observed. To determine whether protection of rd1 photoreceptors by inhibition of
      dopaminergic signaling is a result of conditions specific to the organ culture
      environment, we grew in vitro retinas from the four lines of double mutant mice
      for four weeks. Again, no increase in photoreceptor survival was seen. Finally,
      three triple mutants were generated that lacked two DA receptors (D1/D2; D1/D4;
      and D2/D4) on a rd1 background. In all three cases, rod photoreceptors were not
      protected from degeneration. CONCLUSIONS: The dramatic protection of rd1 rod
      photoreceptors by inhibition of DA signaling in organ culture has not been
      reproduced in vivo by either a pharmacological approach, due to technical
      limitations, or by genetic manipulations. The possible role of compensatory
      effects during retinal development in DA receptor deficient mice is considered.

PMID- 20038976
TI  - Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and
      exfoliation glaucoma.
AB  - PURPOSE: To investigate possible genetic associations of matrix metalloproteinase
      1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with
      (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. METHODS: A
      total of 182 unrelated Greek patients with XFS, including 92 patients with
      XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the
      study. MMP1 -1607 1G/2G (rs1799750) and MMP3 -1171 5A/6A (rs3025058)
      polymorphisms were determined using standard PCR/restriction fragment length
      polymorphism methods. Differences in allele and genotype distributions were
      analyzed using logistic regression. RESULTS: The distribution of genotypes and
      alleles in MMP1 and MMP3 polymorphisms was not significantly different between
      cases with exfoliation syndrome, with or without glaucoma, and controls. However,
      the allele contrast for the MMP1 variant showed a trend for a significant
      association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for
      multiple comparisons, this association was no longer statistically significant.
      CONCLUSIONS: Our study provided some evidence of a possible role of the MMP1
      variant in the development of exfoliation syndrome in Greek patients.

PMID- 20038977
TI  - Specific NFkappaB subunit activation and kinetics of cytokine induction in
      adenoviral keratitis.
AB  - PURPOSE: Corneal inflammation associated with ocular adenoviral infection is
      caused by leukocytic infiltration of the subepithelial stroma in response to
      expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1)
      by infected corneal cells. We have shown that these two chemokines are activated
      by the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated
      kinase (ERK) and p38 for IL-8, and Jun-terminal kinase (JNK) for MCP-1. It is
      also well established that transcription of each of these chemokines is tightly
      controlled by the nuclear factor kappa B (NFkappaB) transcription factor family.
      Therefore, we sought to better understand the differential regulation of
      chemokine expression by NFkappaB in adenoviral infection of the cornea. METHODS:
      Primary keratocytes derived from human donor corneas were treated with signaling
      inhibitors and small interfering RNA specific to MAPKs, and infected with
      adenovirus for different time periods before analysis. Activation of specific
      NFkappaB subunits was analyzed by western blot, confocal microscopy,
      electromobility shift assay, and chromatin immunoprecipitation, and chemokine
      expression was quantified by enzyme-linked immunosorbent assay. RESULTS: Upon
      adenoviral infection, NFkappaB p65, p50, and cREL subunits translocate to the
      nucleus. This translocation is blocked by inhibitors of specific MAPK signaling
      pathways. Confocal microscopy showed that inhibitors of the p38, JNK, and ERK
      pathways differentially inhibited NFkappaB nuclear translocation, while PP2, an
      inhibitor of Src family kinases, completely inhibited NFkappaB nuclear
      translocation. Western blot analysis revealed that activation of specific
      NFkappaB subunits was time dependent following infection. Chromatin
      immunoprecipitation experiments indicated that binding of NFkappaB p65 and p50
      subunits to the IL-8 promoter upon viral infection was differentially reduced by
      chemical inhibitors of MAPKs. Electromobility shift assay and luciferase assay
      analysis revealed that transactivation of IL-8 occurred with binding by the
      NFkappaB p65 homodimer or NFkappaB p65/p50 heterodimer as early as 1 h post
      infection, whereas MCP-1 expression was dependent upon the NFkappaB cREL but not
      the p65 subunit, and occurred 4 h after IL-8 induction. Finally, knockdown of
      NFkappaB p65 by short interfering RNA abrogated IL-8 but not MCP-1 expression
      after adenoviral infection. CONCLUSION: The kinetics of NFkappaB subunit
      activation are partly responsible for the observed pattern of acute inflammation
      in the adenoviral-infected cornea. MAPKs differentially regulate chemokine
      expression in adenoviral keratitis by differential and time-dependent activation
      of specific NFkappaB subunits.

PMID- 20038978
TI  - Helicobacter pylori and gastroduodenal ulcer disease.
AB  - BACKGROUND: Helicobacter pylori-associated diseases and gastroduodenal ulcer
      disease are common conditions of major clinical and economic importance. There is
      thus a need for a guideline that incorporates the scientific knowledge gained in
      recent years and that takes specific aspects of the situation in Germany into
      account with regard to epidemiology, resistance status, diagnostic evaluation,
      and treatment. METHODS: This level-S3 consensus guideline was developed in
      accordance with the recommendations of the Association of Scientific Medical
      Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen
      Fachgesellschaften, AWMF). It was commissioned by the German Association for
      Digestive and Metabolic Diseases (Deutsche Gesellschaft fur Verdauungs- und
      Stoffwechselkrankheiten, DGVS) and prepared in cooperation with other scientific
      societies. After search terms were compiled, a systematic, IT-supported
      literature search was performed in the PubMed and Cochrane databases. The search
      was restricted to articles that appeared in German or English from 2000 onward.
      RESULTS: H. pylori infection can be accurately diagnosed either non-invasively
      (with a (13)C-urea breath test or a stool antigen test) or invasively (with a
      rapid urease test, by histology, or by culture). Gastric and duodenal ulcer and
      gastric MALT lymphoma are absolute indications for eradication therapy; relative
      indications include functional dyspepsia, the prevention of gastric cancer in
      persons at risk, the initiation of long-term treatment with non-steroidal anti
      inflammatory drugs (NSAID), and the prior occurrence of gastroduodenal
      complications with the use of either NSAID or acetylsalicylic acid (ASA). First
      line therapy consists of a proton-pump inhibitor (PPI) and clarithromycin
      combined with either metronidazole or amoxicillin, given for at least one week.
      CONCLUSION: This guideline enables the structured, evidence-based diagnosis and
      treatment of H. pylori infection and associated conditions, as well as of
      gastroduodenal ulcer disease.

PMID- 20038979
TI  - Lung cancer: current diagnosis and treatment.
AB  - BACKGROUND: Much progress has been made in the treatment of lung cancer in the
      last ten years (adjuvant chemotherapy, targeted therapy, individualized therapy).
      Nonetheless, lung cancer is still the leading cause of death due to cancer and
      thus remains a major medical, scientific, and social problem. METHOD: This review
      is based on national and international recommendations and selected articles from
      the literature. RESULTS: Cigarette smoking is the major pathogenic factor for
      lung cancer. Lung cancer can be divided into two major types that differ in their
      biological behavior, small cell lung cancer and non-small cell lung cancer.
      Whenever possible, the diagnosis should be confirmed by biopsy, the extent of
      disease should be documented in detail (international TNM
      classification/staging), and the patient's functional level should be assessed
      with a view toward treatment planning. Surgery for non-small cell lung cancer
      with curative intent is possible up to stage IIIA, while stage IIIB is the domain
      of radiotherapy. Surgery for small cell lung cancer with curative intent is
      possible for rare cases in early stages (T1N0 and T2N0, i.e., stage IA and IB).
      As long as small cell lung cancer is restricted to one side of the chest,
      simultaneous radiation therapy and chemotherapy are indicated. If a malignant
      pleural effusion or distant metastases are present, both lung cancers are treated
      palliatively with platinum-based chemotherapy.

PMID- 20038980
TI  - The effect of introducing rebate contracts to promote generic drug substitution,
      on doctors' prescribing practices.
AB  - BACKGROUND: As of 1 April 2007, pharmacists in Germany filling prescriptions
      covered by the statutory health insurance system (Gesetzliche
      Krankenversicherung, GKV) are required, whenever possible, to dispense a
      preparation that contains the same active substance and for which a rebate
      contract is in effect. The physician can block drug substitution by crossing out
      "aut idem" ("or the like") on the prescription form. The latter option has
      existed since 2002. We studied the possible effect of the introduction of rebate
      contracts on the use of the no-substitution option. METHODS: Three independent
      random samples were taken from the routine data of the Gmunder ErsatzKasse (GEK,
      a statutory health insurance carrier). The samples consisted of 0.5% of the
      insured adult population in the month of October in the years 2006, 2007, and
      2008 (n = 6195; n = 6300; n = 6845). Within these sample groups, all medication
      orders in which the physician could potentially have exercised a no-substitution
      option were selected, and the corresponding prescriptions were examined. RESULTS:
      The percentage of no-substitution prescriptions rose from October 2006 to October
      2007, and then rose still further to October 2008 (14.4%, 18.4%, 19.0%; p for
      trend < 0.0001). Considerable differences were seen between physicians belonging
      to different regional Associations of Statutory Health Insurance Physicians
      (Kassenarztliche Vereinigungen). In about one-quarter of the no-substitution
      prescriptions for 2007 and 2008 (25.1%, 25.7%), the prescribed medication was
      itself included in a rebate contract. CONCLUSIONS: The use of the no-substitution
      option is not uniform across Germany at present. Rebate contracts and the no
      substitution option require further evaluation. Moreover, the dispensing of
      medications urgently needs a more stable regulatory framework.

PMID- 20038981
TI  - Postoperative care following pancreatic surgery: surveillance and treatment.
AB  - BACKGROUND: After pancreatic surgery, some patients have complications that
      require treatment. METHOD: Review article based on a selective literature search
      and the German S3 guideline on pancreatic carcinoma. RESULTS: Detailed knowledge
      of the surgical procedure and its potential early and late complications is a
      prerequisite for the recognition and treatment of problems occurring after
      pancreatic surgery. These may be due either to the operation itself or to the
      progression of the underlying pancreatic disease. Both diabetes mellitus and
      exocrine insufficiency are common long-term sequelae. If persistent pain should
      arise, its cause must be identified and treated. To prevent malnutrition and
      vitamin deficiency after pancreatic resection, patients should be given a diet
      with an increased fat content and with supplemental enzymes. CONCLUSION:
      Appropriate methods are available for the accurate diagnosis and, in most cases,
      successful treatment of complications arising after pancreatic surgery.

PMID- 20038982
TI  - Interpreting results in 2 x 2 tables: part 9 of a series on evaluation of
      scientific publications.
AB  - BACKGROUND: The findings of epidemiological studies, diagnostic tests, and
      comparative therapeutic trials are often presented in 2 x 2 tables. These must be
      interpreted correctly for a proper understanding of the findings. METHODS: The
      authors present basic statistical concepts required for the analysis of nominal
      data, referring to standard works in statistics. RESULTS: The relative risk and
      odds ratio are defined to be indices for the relationship between two binary
      quantities (e.g., exposure--yes/no and disease--yes/no). The topics dealt with in
      this article include the effect of sample size on the length of the confidence
      interval and the p-value, and also inaccuracies caused by measuring error.
      Exposures are often expressed on a three-level scale (none, low, high). The
      authors also consider the 2 x 3 table as an extension of the 2 x 2 table and
      discuss the categorization of continuous measurements. Typically, more than one
      factor is involved in the development of a disease. The effect that a further
      factor can have on the observed relationship between the exposure and the disease
      is discussed. CONCLUSIONS: Sample size, measurement error, categorization, and
      confounders influence the statistical interpretation of 2 x 2 tables in many
      ways. Readers of scientific publications should know the inherent problems in the
      interpretation of simple 2 x 2 tables and check that the authors have taken these
      into account adequately in analyzing and interpreting their data.

PMID- 20038983
TI  - [Cultural patterns of social alcohol use in Buenos Aires' students (Argentina)].
AB  - The turning into an alcoholic state in a group of youngsters at the Province of
      Buenos Aires in relation to the alcohol consumption and the ideal patterns of
      availability are focused in an actual youthful celebration. More than half of the
      students considered amounts of alcohol that surpass 100 cc of absolute alcohol by
      person in each encounter and with different type of drinks. It was registered the
      peer pressure for consumption. It was analyzed the social pattern of the
      consumption in the youthful celebration as a way of managing a social fitness on
      the base of altering the field of the emotions with base in the alcohol abuse.

PMID- 20038984
TI  - [The future of depression: a complex neuroendocrine, inflammatory and
      neurodegenerative systemic illness].
AB  - Neurobiological models of depression have evolved far beyond the monoamine theory
      that was construed following the advent of antidepressant drugs in the 1950s.
      Depression is now seen to implicate a wide range of neurotransmitters, including
      dopamine and glutamate, and virtually the entire central nervous system. Emerging
      evidence is redefining depression as a chronic and systemic illness that may
      impair neuroendocrine function, biological rhythms and immune responses, and one
      which may lead to dementia if left untreated. Different research approaches, from
      molecular biology to clinical studies, have offered new insights into the
      physiological mechanisms involved as well as indications of how effective
      antidepressant therapies may develop in response to these. In addition to well
      established methods, like monoamine reuptake inhibitors and cognitive behavioural
      therapy, these may include non-steroid anti-inflammatory drugs, prescription of
      physical exercise, somatic treatments and a whole new generation of
      antidepressant drugs endowed with original modes of action. As the management of
      depression becomes increasingly multifaceted, clinicians will be able to optimise
      clinical outcomes for their patients by synergistically integrating the multiple
      therapeutic options available.

PMID- 20038985
TI  - [Contemporary epistemology and psychiatric knowledge. Characteristics of late
      modernity: post and hyper].
AB  - The author explores the concept of late modernity, postmodernity and
      hypermodernity, as well as matters of scientific rationality. He discusses the
      current scientific knowledge from an epistemological viewpoint, in order to prove
      that psychiatric knowledge has reflected these questions throughout history and
      so it still does.

PMID- 20038986
TI  - [From symptomatic stability to functional recovery in the pharmacological
      treatment of schizophrenia and unipolar depression].
AB  - This work summarizes the efficacy of pharmacotherapy in the chronic course of
      schizophrenia and unipolar depresion. It is aimed to answer three questions: does
      it cure these diseases? Does it exert any significant effect on the symptomatic
      presentation of the disorders? Which is its action on the social dysfunction
      provoked by schizophrenia or depression? A conceptual analysis of available
      bibliography was performed. It could be concluded that antypsychotics improve the
      symptomatic course of schizophrenia, although their efficacy is limited, and that
      these drugs does not act on the social dysfunction provoked by the disease. With
      respect to depression, it could be concluded that a significant proportion of
      patients remain symptomatic despite receiveng adequate treatments. No data about
      efficacy of pharmacotherapy on the dysfunction resultant from unipolar depression
      is available.

PMID- 20038987
TI  - [Ups and downs of chronicity: policies, institutions, mechanisms and therapists].
AB  - Chronicity is approached from several angles: that of the individual patient, the
      sociopolitical background, the therapist's role, the institutional framework for
      the treatment of chronic patients. Relevant themes are discussed and authors
      visited that contribute to fresh thinking regarding the position of the therapist
      (psychiatrist, psychologist, psychoanalyst) towards these patients. More often
      than not, these patients are classified as unclassifiable, or refractory. As it
      has been said before, this implies that from the professional's viewpoint these
      patients are intrinsically difficult and "little rewarding". This raises the
      question of health ideals and expectations, as well as the institutional
      inconveniences of current models of treatments and institutional devices.

PMID- 20038988
TI  - [The social construction of dementia: an hypothesis].
AB  - The purpose of this paper is to discuss some ideas concerning the relationship
      between dementia and the role people with it play in the society. I develop some
      examples from literature and medical authors such as Sacks, King, Franzen, Post,
      etc., avoiding conventional perspectives about this disease. The objective is to
      show a new "dementia culture" against our "hypercognitive society".

PMID- 20038989
TI  - [The impact on clinical practice of the concept of chronicity].
AB  - Studies of higher level of evidence show that the clinic of chronic diseases such
      as schizophrenia or bipolar disorder is not crystallized and is liable to be
      changed positively by pharmacological and psychosocial interventions. Supporting
      the concept of chronicity or "clinical unchangeable", not being supported by
      scientific evidence, lies in the way of belief or prejudice. Thinking that
      chronic diseases can't be improved by therapeutic interventions may result in not
      offering treatment options. We could be facing a chronicity generated in the
      minds of colleagues and not in the scope of the clinical patients. The beliefs
      and prejudices of professionals in the mental health field might have a
      stigmatizing effect similar to that of the general population. Intense antistigma
      activity is needed not only in the general public but also within our field. The
      clarification of the concept of chronicity is located on this line.

PMID- 20038990
TI  - [Harold Searles: a commitment to life with schizophrenic patients].

PMID- 20038991
TI  - [A study of level of knowledge about depressive disorders among general
      practitioners in Argentina].
AB  - OBJECTIVES: To determine the level of knowledge about depressive disorders
      including their treatment, comorbidities and suicide potential among a number of
      general practitioners who agreed to fill out a questionnaire and provided
      information about their professional activities. METHOD: Exploratory cross
      sectional study among a number of general practitioners who answered voluntarily
      and anonymously to a questionnaire consisting of twelve questions. Data collected
      from 288 physicians were analyzed. RESULTS: The majority of physicians (97.6%,
      n=281) considered that depression was a disease, but 39.6% (n=114) believed that
      it was caused by lack of will power or characterological weaknesses, which create
      a dissonance with the concept of disease. They also felt that they did not have
      enough knowledge about Depressive Disorders such as their origins, type of
      medications and length of treatment, comorbidities and suicide potential.
      CONCLUSIONS: The results point to the need for continuous medical education about
      Depressive Disorders among general practitioners.

PMID- 20038992
TI  - [Quality life of working health care professionals].
AB  - In this article the author presents the theoretical concepts of quality of life,
      labor satisfaction, and service professions. Then describes the politic
      institution characteristics of the actual national context in which the
      professionals that work in the Health field, developed their daily work. Presents
      a proposal of indicators, specially constructed by the author to analyze the
      labor context, that are being used in different research projects she developed
      since the beginning on XXI century. Finally presents the necessity of generate
      project that considers protagonist points of view and allow the construct of
      diagnosis of the situation, that generate public policies to answer the problem.

PMID- 20038993
TI  - [Initiation cocaine use in elderly patients: a case report].
AB  - INTRODUCTION: Cocaine use is an uncommon condition in older people, a population
      in which cocaine use is probably overlooked. Cases initiation of use in late
      adulthood as well as elderly relapsing to use from youth drug use have been
      reported. CLINICAL CASE: We report a woman of 61 years of age hospitalized in the
      detoxification unit for cocaine dependence tratment (used 1-1,5g/ day). She did
      not begin cocaine use until she was 60 years old. Some risk factors include
      retirement, chronic pain, and affective symptoms are related with loneliness and
      increased cocaine use in elderly, and account for the underreporting of abuse or
      dependence. Old people have more medical conditions related to cocaine use and
      have greater health deterioration than young people. DISCUSION: Cocaine use
      should be evaluated in every patient, and elderly patients should be checked
      particularly when presenting atypical medical or psychiatric conditions.

PMID- 20038994
TI  - [Vital exhaustion is significantly linked to acute coronary events in Argentine
      population].
AB  - OBJECTIVE: To determine the strength of the association between the Vital
      exhaustion syndrome (VES) and acute coronary ischemic events in hospitalized
      Argentinean sample. METHODS: VES was measured in 180 patients of both sexes, 90
      admitted due to an acute coronary ischemic syndrome (AMI or unstable angina) and
      a control group of 90 admitted due to an acute non-coronary cardiac event. VES
      was evaluated with the Maastricht questionnaire during the first week of
      hospitalization. RESULTS: Dividing the sample in two categories: exhausted and
      non-exhausted, 57 (63,33%) of the coronary were exhausted, while among the non
      coronary group, 33 were exhausted (36,66%)(OR=3.1 (1.7-5.8)). The exhaustion
      score was: control mean score: 17,1 (sd 8,96); case mean score: 21,1 (sd10,60) p:
      0.006. Dislipemia was another factor with a significant difference: control 27
      (30%) case 44 (62%) OR= 2.2 (1.2-4.1) p=0.01. Logistic regression was performed,
      including an interaction model between DLP and exhaustion, and it did not show a
      significant effect. CONCLUSIONS: Our results indicate that in Argentina, among
      other countries as reported in the literature, VES is a psychological condition
      that is strongly and independent associated to acute coronary events.

PMID- 20038995
TI  - [The process of institutional transformation of San Luis Psychiatric Hospital].
AB  - This article focuses on the human and institutional contradictions involved in
      the transformation process of a classic psychiatric hospital in the province of
      San Luis, Argentina. This process has to resolve clinical, cultural, ideological,
      political conflicts, in the heart of the chosen path, in order to affirm the
      existence of the mental illness, the need to find new treatments for the new
      sufferings involved in leaving enclosure opting for freedom and the accompaniment
      of those who suffer.

PMID- 20038996
TI  - [Qualitative evaluation of the alcoholism integral approach with the GIA model
      (alcoholism institutional groups)].
AB  - This paper presents the evaluation, over a period of 6 years, on the
      effectiveness of the Alcoholism Institutional Group (GIA), in the Puerto San
      Julian Hospital, Santa Cruz, Argentina. The theoretical framework refers to three
      aspects: subject, social and institutional order. The qualitative logic and the
      process of analytic induction were used. METHODOLOGY: information was gathered
      through semi-structured interviews to selected cases (intentional sampling). The
      constant comparative method for the analysis was used. RESULTS: the GIA method is
      effective from the aspects of the subject and the social order; the subject
      included in the treatment was able to: a) deconstruct the socially assumed role
      as an alcoholic, b) reconstruct their identity, c) restore the fabric of family,
      labour and social links, d) identify the healthy aspects of their personality to
      recover the capacities obstructed by the illness, e) learn to solve conflicts
      collectively thanks to group functioning, f) report to destigmatize the illness,
      and g) develop a healthy life project. The GIA method proved partially effective
      from the institutional angle; the task succeeded in uncovering, affirming and
      working on alcoholism as an illness within the hospital setting, but with less
      involvement than other local institutions, which motivated projects and
      strategies started from the results of this research.

PMID- 20038997
TI  - ["Open Door". A praxis for a new paradigm].
AB  - This paper describes the global situation regarding mental health care and legal
      regulations in force, and emphasizes the need to rethink policies in order to
      apply World Health Organization's recommendations in Argentina. In this context,
      it considers the prevailing mental health systems as trapped in a oversimplified
      paradigm in relation to health-disease-attention procedures, and their ways of
      intervention in patients, which erodes these procedures and make professionals
      uncomfortable. So this paper promotes a new intervention paradigm which takes
      into account the complexity of the phenomenona, and stresses its relational
      aspects, the importance of professional training while in service, the inclusion
      of new actors, and a change in the whole institutional culture. So it proposes
      the development of a program which intervenes in critical situations while
      granting a humanized, inclusive, and respectful of human rights system.

PMID- 20038998
TI  - [The WHO and the challenges in Mental Health].

PMID- 20039000
TI  - [The modern asylum in the doctoral thesis of Norberto Maglioni (1879)].

PMID- 20038999
TI  - [From the asylums to the community: the reform process of National Colony "Dr.
      Manuel A. Montes de Oca"].
AB  - Since 2004, a profound transformation of the asylum care model, characterized by
      overcrowding, lack of discharge and absence of rehabilitation programs, and
      social reinsertion, has been developed at National Colony "Dr. Manuel A. Montes
      de Oca". During this period, a plan that contemplates several programs and
      projects aimed at restoring the rights of institutionalized people with mental
      disabilities and promoting opportunities for social inclusion has been
      implemented.

PMID- 20039001
TI  - [The asylums].

PMID- 20039002
TI  - The relevance of C-Peptide in diabetes and its complications: an introduction to
      the special issue.

PMID- 20039003
TI  - C-Peptide and its intracellular signaling.
AB  - Although long believed to be inert, C-peptide has now been shown to have definite
      biological effects both in vitro and in vivo in diabetic animals and in patients
      with type 1 diabetes. These effects point to a protective action of C-peptide
      against the development of diabetic microvascular complications. Underpinning
      these observations is undisputed evidence of C-peptide binding to a variety of
      cell types at physiologically relevant concentrations, and the downstream
      stimulation of multiple cell signaling pathways and gene transcription via the
      activation of numerous transcription factors. These pathways affect such
      fundamental cellular processes as re-absorptive and/or secretory phenotype,
      migration, growth, and survival. Whilst the receptor remains to be identified,
      experimental data points strongly to the existence of a specific G-protein
      coupled receptor for C-peptide. Of the cell types studied so far, kidney tubular
      cells express the highest number of C-peptide binding sites. Accordingly, C
      peptide exerts major effects on the function of these cells, and in the context
      of diabetic nephropathy appears to antagonise the pathophysiological effects of
      major disease mediators such as TGFbeta1 and TNFalpha. Therefore, based on its
      cellular activity profile C-peptide appears well positioned for development as a
      therapeutic tool to treat microvascular complications in type 1 diabetes.

PMID- 20039004
TI  - A Molecular Level Understanding of Zinc Activation of C-peptide and its Effects
      on Cellular Communication in the Bloodstream.
AB  - Inspired by previous reports, our group has recently demonstrated that C-peptide
      exerts beneficial effects upon interactions with red blood cells (RBCs). These
      effects can be measured in RBCs obtained from animal models of both type 1
      diabetes and type 2 diabetes, though to different extents. To date, the key
      metrics that have been measured involving C-peptide and RBCs include an increase
      in glucose uptake by these cells and a subsequent increase in adenosine
      triphosphate (ATP) release. Importantly, to date, our group has only been able to
      elicit these beneficial effects when the C-peptide is prepared in the presence of
      Zn2+. The C-peptide-induced release of ATP is of interest when considering that
      ATP is a purinergic signaling molecule known to stimulate the production of
      nitric oxide (NO) in the endothelium and in platelets. This NO production has
      been shown to participate in smooth muscle relaxation and subsequent vessel
      dilation. Furthermore, NO is a well-established platelet inhibitor. The objective
      of this review is to provide information pertaining to C-peptide activity on
      RBCs. Special attention is paid to the necessity of Zn2+ activation, and the
      origin of that activation in vivo. Finally, a mechanism is proposed that explains
      how C-peptide is exerting its effects on other cells in the bloodstream,
      particularly on endothelial cells and platelets, via its ability to stimulate the
      release of ATP from RBCs.

PMID- 20039005
TI  - Molecular effects of C-Peptide in microvascular blood flow regulation.
AB  - C-Peptide is produced in beta-cells in the pancreas, and secreted into the blood
      stream in equimolar amounts with insulin. For a long time, C-peptide was
      considered as an important component in the biosynthesis of insulin, but
      otherwise believed to possess minimal biological activity. In the recent years,
      numerous studies demonstrated that lacking C-peptide in type 1 diabetic patients
      might exert an important role in the development of microvascular complications
      such as nephropathy or neuropathy. There is increasing evidence that the
      biological effects of C-peptide are, at least in part, mediated through the
      modulation of endothelial function and microvascular blood flow. In several
      tissues, an increase in microvascular and nutritional blood flow could be
      observed during substitution of physiological amounts of C-peptide. Recent
      studies confirmed that C-peptide stimulates endothelial NO release by the
      activation of Ca2+ calmodulin-regulated endothelial NO synthase. A restoration of
      Na+/K+-ATPase activity during C-peptide supplementation could be observed in
      erythrocytes and renal tubular cells. The improvement of erythrocyte Na+/K+
      ATPase is associated with an increase in erythrocyte deformability, and improved
      rheological properties. In this article, we consider the role of C-peptide in the
      context of endothelial function and microvascular blood flow as pathophysiologic
      components in the development of microvascular complications in patients with
      diabetes mellitus and loss of beta-cell function.

PMID- 20039006
TI  - Anti-inflammatory properties of C-Peptide.
AB  - C-peptide, historically considered a biologically inactive peptide, has been
      shown to exert insulin-independent biological effects on a number of cells
      proving itself as a bioactive peptide with anti-inflammatory properties. Type 1
      diabetic patients typically lack C-peptide, and are at increased risk of
      developing both micro- and macrovascular complications, which account for
      significant morbidity and mortality in this population. Inflammatory mechanisms
      play a pivotal role in vascular disease. Inflammation and hyperglycemia are major
      components in the development of vascular dysfunction in type 1 diabetes. The
      anti-inflammatory properties of C-peptide discovered to date are at the level of
      the vascular endothelium, and vascular smooth muscle cells exposed to a variety
      of insults. Additionally, C-peptide has shown anti-inflammatory properties in
      models of endotoxic shock and type 1 diabetes-associated encephalopathy. Given
      the anti-inflammatory properties of C-peptide, one may speculate dual hormone
      replacement therapy with both insulin and C-peptide in patients with type 1
      diabetes may be warranted in the future to decrease morbidity and mortality in
      this population.

PMID- 20039007
TI  - C-Peptide in the vessel wall.
AB  - Patients with insulin resistance and early type 2 diabetes exhibit an increased
      sensitivity to develop a diffuse and extensive pattern of arteriosclerosis
      leading to a remarkable increase in vascular complications, including myocardial
      infarction and stroke. The accelerated atherosclerosis in these patients is
      likely to be multifactorial. In this review, we introduce the new hypothesis that
      C-peptide could play a role as a mediator of lesion development. Patients with
      type 2 diabetes show increased levels of the proinsulin cleavage product C
      peptide, and in the past few years, various groups have examined the effect of C
      peptide in vascular cells as well as its potential role in lesion development.
      Recent data suggest that C-peptide deposits in the vessel wall could promote the
      recruitment of monocytes and CD4-positive lymphocytes in early arteriosclerotic
      lesions. Furthermore, C-peptide induces proliferation of vascular smooth muscle
      cells, a critical step in atherogenesis and restenosis formation. The present
      review summarizes this new pathophysiological aspect and discusses the potential
      relevance for lesion development.

PMID- 20039008
TI  - The beneficial effects of C-Peptide on diabetic polyneuropathy.
AB  - Diabetic polyneuropathy (DPN) is a common complication in diabetes. At present,
      there is no adequate treatment, and DPN is often debilitating for patients. It is
      a heterogeneous disorder and differs in type 1 and type 2 diabetes. An important
      underlying factor in type 1 DPN is insulin deficiency. Proinsulin C-peptide is a
      critical element in the cascade of events. In this review, we describe the
      physiological role of C-peptide and how it provides an insulin-like signaling
      function. Such effects translate into beneficial outcomes in early metabolic
      perturbations of neural Na+/K+-ATPase and nitric oxide (NO) with subsequent
      preventive effects on early nerve dysfunction. Further corrective consequences
      resulting from this signaling cascade have beneficial effects on gene regulation
      of early gene responses, neurotrophic factors, their receptors, and the insulin
      receptor itself. This may lead to preventive and corrective results to nerve
      fiber degeneration and loss, as well as, promotion of nerve fiber regeneration
      with respect to sensory somatic fibers and small nociceptive nerve fibers. A
      characteristic abnormality of type 1 DPN is nodal and paranodal degeneration with
      severe consequences for myelinated fiber function. This review deals in detail
      with the underlying insulin-deficiency-related molecular changes and their
      correction by C-peptide. Based on these observations, it is evident that
      continuous maintenance of insulin-like actions by C-peptide is needed in
      peripheral nerve to minimize the sequences of metabolic and molecular
      abnormalities, thereby ameliorating neuropathic complications. There is now ample
      evidence demonstrating that C-peptide replacement in type 1 diabetes promotes
      insulin action and signaling activities in a more enhanced, prolonged, and
      continuous fashion than does insulin alone. It is therefore necessary to replace
      C-peptide to physiological levels in diabetic patients. This will have
      substantial beneficial effects on type 1 DPN.

PMID- 20039009
TI  - C-Peptide: the missing link in diabetic nephropathy?
AB  - Proinsulin C-peptide has been found to exert beneficial effects in many tissues
      affected by diabetic microvascular complications, including the kidneys.
      Glomerular hyperfiltration and microalbuminuria are early markers of diabetic
      nephropathy. C-peptide at physiological concentrations effectively reduces
      diabetes-induced glomerular hyperfiltration via constriction of the afferent
      arteriole, dilation of the efferent arteriole, and inhibition of tubular
      reabsorption in experimental models of type 1 diabetes. The glomerular
      hypertrophy and mesangial matrix expansion seen in early diabetes can be reduced
      or prevented by C-peptide administration, possibly via interference with TGF
      beta1 and TNFalpha signaling. Several of C-peptide's reno-protective effects have
      been confirmed in human studies; reduced glomerular hyperfiltration and
      diminished urinary albumin excretion have been documented in type 1 diabetes
      patients receiving replacement doses of C-peptide for periods of up to 3 months.
      In this review, we critically summarize the current state of knowledge regarding
      C-peptide's renal effects, and discuss possible mechanisms of its beneficial
      effects in diabetic nephropathy.

PMID- 20039010
TI  - Sequential abnormalities in type 1 diabetic encephalopathy and the effects of C
      Peptide.
AB  - Diabetic encephalopathy is a recently recognized complication in type 1 diabetes.
      In this review, we summarize a series of experimental results obtained
      longitudinally in the spontaneously type 1 diabetic BB/Wor-rat, and bringing out
      the beneficial effects of C-peptide replacement. It is increasingly clear that
      lack of insulin and C-peptide, and perturbations of their signaling cascades in
      type 1 diabetes are detrimental to the regulation of neurotrophic factors and
      their receptors. Other consequences of such deficits and perturbations are innate
      inflammatory responses with effects on synaptogenesis, neurite degeneration, and
      early behavioral abnormalities. Replacement of C-peptide, which does not effect
      hyperglycemia, has beneficial effects on a variety of pro-apoptotic stressors,
      oxidative stressors, and finally on apoptosis. Eventually, this cascade of events
      leads to neuronal loss and decreased densities of white matter myelinating cells,
      with more profound deficits in behavioral and cognitive function. Such changes
      are likely to underlie gray and white matter atrophy in type 1 diabetes, and are
      significantly prevented by full C-peptide replacement. Present data demonstrate
      that C-peptide replacement has beneficial effects on numerous sequential and
      partly interrelated pathogenetic mechanisms, resulting in prevention of neuronal
      and oligodendroglial cell loss, with significant prevention of neurobehavioral
      and cognitive functions.

PMID- 20039011
TI  - C-Peptide is Relevant in Type 1 Diabetes and its Complications: Summary and
      Conclusions to the Special Issue.

PMID- 20039012
TI  - Night work and breast cancer - results from the German GENICA study.
AB  - OBJECTIVES: Some epidemiological and animal data indicate that night work might
      increase the risk for breast cancer. We have investigated the risk in a German
      population-based case-control study known as GENICA (gene environment interaction
      and breast cancer). METHODS: The GENICA study involved interviews to assess shift
      work information in 857 breast cancer cases and 892 controls. We estimated risks
      of employment status and night shift characteristics using conditional logistic
      regression models, adjusting for potential confounders. Resampling and
      bootstrapping were applied to adjust the risk estimates for a potential selection
      bias. RESULTS: Among 1749 women, 56 cases and 57 controls worked in night shifts
      for > or =1 year, usually in the healthcare sector (63.0% of controls). Female
      night workers were more frequently nulliparous and low-educated than day workers
      (28.6% versus 17.8% and 12.3% versus 9.2%, respectively). Fewer women in night
      work had ever used post-menopausal hormone therapy (35.7% versus 51.9%). An
      elevated breast cancer risk was not associated with having ever done shift or
      night work when compared to women employed in day work only [odds ratio (OR)
      0.96, 95% confidence interval (95% CI) 0.67-1.38 and OR 0.91, 95% CI 0.55-1.49,
      respectively). Women who reported >807 night shifts, the third quartile of the
      distribution among controls, experienced a breast cancer risk of 1.73 (95% CI
      0.71-4.22). Night work for > or =20 years was associated with an OR of 2.48 (95%
      CI 0.62-9.99) based on 12 cases and 5 controls. CONCLUSIONS: Long-term night work
      was associated with a modestly, but not significantly, increased breast cancer
      risk, while having ever done night work was not. The precision of the results was
      limited by a low prevalence of night work in this study population.

PMID- 20039013
TI  - A single recessive gene controls cadmium translocation in the cadmium
      hyperaccumulating rice cultivar Cho-Ko-Koku.
AB  - The heavy metal cadmium (Cd) is highly toxic to humans and can enter food chains
      from contaminated crop fields. Understanding the molecular mechanisms of Cd
      accumulation in crop species will aid production of safe Cd-free food. Here, we
      identified a single recessive gene that allowed higher Cd translocation in rice,
      and also determined the chromosomal location of the gene. The Cd hyperaccumulator
      rice variety Cho-Ko-Koku showed 3.5-fold greater Cd translocation than the no
      accumulating variety Akita 63 under hydroponics. Analysis of an F(2) population
      derived from these cultivars gave a 1:3 segregation ratio for high:low Cd
      translocation. This indicates that a single recessive gene controls the high Cd
      translocation phenotype. A QTL analysis identified a single QTL, qCdT7, located
      on chromosome 7. On a Cd-contaminated field, Cd accumulation in the F(2)
      population showed continuous variation with considerable transgression. Three
      QTLs for Cd accumulation were identified and the peak of the most effective QTL
      mapped to the same region as qCdT7. Our data indicate that Cd translocation
      mediated by the gene on qCdT7 plays an important role in Cd accumulation on
      contaminated soil.

PMID- 20039014
TI  - Dehydrin variants associated with superior freezing tolerance in alfalfa
      (Medicago sativa L.).
AB  - A cDNA (msaCIG) encoding a cold-inducible Y(2)K(4) dehydrin in alfalfa (Medicago
      sativa spp. sativa) was shown to share extensive homology with sequences from
      other species and subspecies of Medicago. Differences were mainly the result of
      the occurrence of large indels, amino acids substitutions/deletions and sequence
      duplications. Using a combination of a bulk segregant analysis and RFLP
      hybridization, we uncovered an msaCIG polymorphism that increases in frequency in
      response to recurrent selection for superior freezing tolerance. Progenies from
      crosses between genotypes with (D+) or without (D-) the polymorphic dehydrin
      significantly differed in their tolerance to subfreezing temperatures. Based on
      the msaCIG sequence, we looked for intragenic variations that could be associated
      to the polymorphism detected on Southern blots. Amplifications with primers
      targeting the 3' half side of msaCIG revealed fragment size variations between
      pools of genotypes with (+) or without (-) the polymorphism. Three major groups
      of amplicons of approximately 370 nt (G1), 330 nt (G2), and 290 nt (G3) were
      distinguished. The G2 group was more intensively amplified in pools of genotypes
      with the polymorphic dehydrin and was associated to a superior freezing tolerance
      phenotype. Sequences analysis revealed that size variation in the 3' half was
      attributable to the variable occurrence of large indels. Single amino acid
      substitutions and/or deletions caused major differences in the prediction of the
      secondary structure of the polypeptides. The identification of dehydrin variants
      associated to superior freezing tolerance paves the way to the development of
      functional markers and the fixation of favorable alleles in various genetic
      backgrounds.

PMID- 20039015
TI  - Assessment of genetic diversity of accessions in Brassicaceae genetic resources
      by frequency distribution analysis of S haplotypes.
AB  - Plant genetic resources are important sources of genetic variation for improving
      crop varieties as breeding materials. Conservation of such resources of
      allogamous species requires maintenance of the genetic diversity within each
      accession to avoid inbreeding depression and loss of rare alleles. For assessment
      of genetic diversity in the self-incompatibility locus (S locus), which is
      critically involved in the chance of mating, we developed a dot-blot genotyping
      method for self-incompatibility (S) haplotypes and applied it to indigenous,
      miscellaneous landraces of Brassica rapa, provided by the IPK Gene Bank
      (Gatersleben, Germany) and the Tohoku University Brassica Seed Bank (Sendai,
      Japan), in which landraces are maintained using different population sizes. This
      method effectively determined S genotypes of more than 500 individuals from the
      focal landraces. Although our results suggest that these landraces might possess
      sufficient numbers of S haplotypes, the strong reduction of frequencies of
      recessive S haplotypes occurred, probably owing to genetic drift. Based on these
      results, we herein discuss an appropriate way to conserve genetic diversity of
      allogamous plant resources in a gene bank.

PMID- 20039016
TI  - Cadmium content of commercial and contaminated rice, Oryza sativa, in Thailand
      and potential health implications.
AB  - Thailand is the number one global exporter and among the top five producers of
      rice in the world. A significant increase in anthropogenic contamination in
      agricultural soils over the past few decades has lead to concerns with cadmium
      and its uptake in rice. The cadmium levels in Thai rice from different
      sources/areas were determined and used to estimate the potential health risks to
      consumers. The cadmium concentration in the commercial rice samples ranged from
      below the detection limit to 0.016 mg/kg. The cadmium concentrations in the
      contaminated rice samples ranged from a low of 0.007 mg/kg to a high of 0.579
      mg/kg. Five of the calculated values exceed the proposed PTWI, with one value
      almost three times higher and two values almost double. The three highly elevated
      values are certainly a concern from a health standpoint. Ultimately, action is
      required to address the health implications resulting from the cadmium
      contamination in agricultural soils used for rice production in a few select
      areas of Thailand. Overall, this study indicates that the vast majority of rice
      produced, consumed and exported by Thailand is safe pertaining to cadmium
      content.

PMID- 20039017
TI  - Dietary intake of total and inorganic arsenic by adults in arsenic-contaminated
      area of Ron Phibun district, Thailand.
AB  - Ron Phibun District, approximately 800 km south of Bangkok, is the site of tin
      mines operated almost 100 years ago. As a result of mining activities, arsenic
      contaminated the soil and groundwater of the district. The specific aim of this
      study was to estimate the dietary intakes of total and inorganic arsenic in 20
      adults (10 males and 10 females) residing in Ron Phibun District by a duplicate
      food approach for 7-consecutive days. The weekly intake rates of inorganic
      arsenic ranged from 5.54 to 13.3 microg/kg BW for males and 6.11-12.1 microg/kg
      BW for females.

PMID- 20039018
TI  - Persistence of trifloxystrobin and tebuconazole on grape leaves, grape berries
      and soil.
AB  - Following four foliar applications of Nativo 75 WG (trifloxystrobin 25% +
      tebuconazole 50%) on grapes @ 175 and 350 g/ha, resulting in active applications
      of trifloxystrobin @ 43.75 and 87.5 g a.i./ha and that of tebuconazole @ 87.5 and
      175 g a.i./ha, the average initial deposits of trifloxystrobin were observed to
      be 7.76 and 15.53 mg/kg, respectively, at single and double the application
      rates. These residue levels dissipated to >85% after 10 days of its application
      at both the dosages. Similarly, the average initial deposits of tebuconazole were
      observed to be 13.84 and 26.55 mg/kg at single and double the application rate,
      respectively. These residue levels dissipated to >90% after 10 days of
      application at both the dosages. The half-life (t(1/2)) periods of
      trifloxystrobin on grape leaves were observed to be 2.92 and 3.48 days at single
      and double application rates, respectively, whereas these values were 2.68 and
      3.96 days for tebuconazole. Ripe grape berries and soil samples collected at
      harvest which happened to be 34 days after the last application, did not show the
      presence of residues of trifloxystrobin and tebuconazole at their determination
      limit of 0.01 and 0.02 mg/kg, respectively.

PMID- 20039019
TI  - Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of chanoclavine
      I to chanoclavine-I aldehyde catalyzed by a short-chain alcohol dehydrogenase
      FgaDH.
AB  - Ergot alkaloids are toxins and important pharmaceuticals which are produced
      biotechnologically on an industrial scale. A putative gene fgaDH has been
      identified in the biosynthetic gene cluster of fumigaclavine C, an ergot alkaloid
      of the clavine-type. The deduced gene product FgaDH comprises 261 amino acids
      with a molecular mass of about 27.8 kDa and contains the conserved motifs of
      classical short-chain dehydrogenases/reductases (SDRs), but shares no worth
      mentioning sequence similarity with SDRs and other known proteins. The coding
      region of fgaDH consisting of two exons was amplified by PCR from a cDNA library
      of Aspergillus fumigatus, cloned into pQE60 and overexpressed in E. coli. The
      soluble tetrameric His(6)-FgaDH was purified to apparent homogeneity and
      characterized biochemically. It has been shown that FgaDH catalyzes the oxidation
      of chanoclavine-I in the presence of NAD(+) resulting in the formation of
      chanoclavine-I aldehyde, which was unequivocally identified by NMR and MS
      analyzes. Therefore, FgaDH functions as a chanoclavine-I dehydrogenase and
      represents a new group of short-chain dehydrogenases. K (M) values for
      chanoclavine-I and NAD(+) were determined at 0.27 and 1.1 mM, respectively. The
      turnover number was 0.38 s(-1).

PMID- 20039020
TI  - Genome organisation of the marine Roseobacter clade member Marinovum algicola.
AB  - The Roseobacter clade, belonging to the family Rhodobacteraceae of the class
      Alphaproteobacteria, is one of the major bacterial groups in marine environments.
      A remarkable wealth of diverse large plasmids has been detected in members of
      this lineage. Here, we analysed the genome structure and extrachromosomal DNA
      content of four strains of the roseobacter species Marinovum algicola by pulsed
      field gel electrophoresis. They were originally isolated from toxic
      dinoflagellates and possess multireplicon genomes with sizes between 5.20 and
      5.35 Mb. In addition to the single circular chromosomes (3.60-3.74 Mb), whose
      organisation seem to be conserved, 9 to 12 extrachromosomal replicons have been
      detected for each strain. This number is unprecedented for roseobacters and
      proposes a sophisticated regulation of replication and partitioning to ensure
      stable maintenance. The plasmid lengths range from 7 to 477 kb and our analyses
      document a circular conformation for all but one of them, which might represent a
      linear plasmid-like prophage. In striking contrast to other roseobacters, up to
      one-third of the genomic information (1.75 Mb) is plasmid borne in Marinovum
      algicola. The plasmid patterns of some strains are conspicuously different,
      indicating that recombination and conjugative gene transfer are dominant
      mechanisms for microevolution within the Roseobacter clade.

PMID- 20039021
TI  - Abstinence-dependent transfer of lithium chloride-induced sucrose aversion to a
      sucrose-paired cue in rats.
AB  - RATIONALE: Responding for a drug- or sucrose-paired cue increases over forced
      abstinence (incubation of craving). If the incentive value of a cue depends on
      the incentive value of the primary reward, devaluing the primary reward should
      reduce cue reactivity. OBJECTIVES: We investigated whether conditioned taste
      aversion (CTA) to sucrose would transfer to a sucrose-paired cue after 1 or 30
      days of forced abstinence and whether CTA after 1 day of forced abstinence would
      affect incubation of craving. MATERIALS AND METHODS: Rats self-administered 10%
      sucrose paired with a tone + light cue for 10 days. After 1 (Exp.1) or 30 (Exp.2)
      days of forced abstinence, rats received two home-cage pairings of sucrose with
      either LiCl (65 mg/kg, IP) to produce CTA or saline as a control. Two days later,
      rats responded for the cue alone. The following day, sucrose consumption was
      assessed in the same operant conditioning chamber. Exp.1 rats were tested again 1
      month later to determine if CTA would affect incubation of craving. RESULTS:
      Exp.1: CTA after 1 day of forced abstinence did not attenuate cue reactivity when
      tested immediately after CTA, nor did the treatment affect incubation of craving
      or incubation of sucrose consumption. Exp.2: CTA after 1 month of forced
      abstinence resulted in a significant reduction in cue reactivity. CONCLUSION: The
      incentive values of sucrose and the conditioned representation of sucrose
      increase over an extended period of forced abstinence. This incubation appears to
      facilitate the transfer of an aversion to the primary reward to the conditioned
      cue.

PMID- 20039022
TI  - Identification of a new co-crystal of salicylic acid and benzamide of
      pharmaceutical relevance.
AB  - Raman spectroscopy, X-ray powder diffraction/X-ray crystallography and
      differential scanning calorimetry have been used to study the phenomenon of co
      crystal formation in stoichiometric mixtures of salicylic acid with benzamide.
      Raman spectroscopy was particularly useful for the characterization of the
      products and was used to determine the nature of the interactions in the co
      crystals. It was observed that little change in the vibrational modes associated
      with the phenyl groups of the respective reactants took place upon co-crystal
      formation, but changes in intensities of the vibrational modes associated with
      the amide and the carboxylic acid groups were observed upon co-crystal formation.
      Several new vibrational bands were identified in the co-crystal which were not
      manifested in the physical mixture of both components and could be used as
      diagnostic features of co-crystal formation.

PMID- 20039023
TI  - Functional abnormalities in normally appearing athletes following mild traumatic
      brain injury: a functional MRI study.
AB  - Memory problems are one of the most common symptoms of sport-related mild
      traumatic brain injury (MTBI), known as concussion. Surprisingly, little research
      has examined spatial memory in concussed athletes given its importance in
      athletic environments. Here, we combine functional magnetic resonance imaging
      (fMRI) with a virtual reality (VR) paradigm designed to investigate the
      possibility of residual functional deficits in recently concussed but
      asymptomatic individuals. Specifically, we report performance of spatial memory
      navigation tasks in a VR environment and fMRI data in 15 athletes suffering from
      MTBI and 15 neurologically normal, athletically active age matched controls. No
      differences in performance were observed between these two groups of subjects in
      terms of success rate (94 and 92%) and time to complete the spatial memory
      navigation tasks (mean = 19.5 and 19.7 s). Whole brain analysis revealed that
      similar brain activation patterns were observed during both encoding and
      retrieval among the groups. However, concussed athletes showed larger cortical
      networks with additional increases in activity outside of the shared region of
      interest (ROI) during encoding. Quantitative analysis of blood oxygen level
      dependent (BOLD) signal revealed that concussed individuals had a significantly
      larger cluster size during encoding at parietal cortex, right dorsolateral
      prefrontal cortex, and right hippocampus. In addition, there was a significantly
      larger BOLD signal percent change at the right hippocampus. Neither cluster size
      nor BOLD signal percent change at shared ROIs was different between groups during
      retrieval. These major findings are discussed with respect to current hypotheses
      regarding the neural mechanism responsible for alteration of brain functions in a
      clinical setting.

PMID- 20039024
TI  - Ocular pursuit and the estimation of time-to-contact with accelerating objects in
      prediction motion are controlled independently based on first-order estimates.
AB  - The present study examined for the first time both the ocular and manual
      responses in a prediction motion (PM) task requiring participants to estimate
      time-to-contact (TTC) of an accelerating object. Results showed that while the
      ocular response initially matched well the object motion, smooth pursuit decayed
      towards zero following object occlusion, during which participants exhibited a
      saccadic response that placed the eyes in the region of the point of contact. The
      primary saccade was completed in advance of the object reaching the point of
      contact, and was best predicted by a first-order estimate of TTC (TTC1).
      Participants then made their manual response, which was also best predicted by
      TTC1. Therefore, object acceleration was not taken into account in either the
      ocular or manual response, with the latter occurring before the object reached
      the point of contact when it decelerated and after when it accelerated. Further
      analyses of the ocular and manual responses indicated no functional relationship
      and independent control. We suggest that the demand to make temporal estimates
      with a stationary location in PM tasks is critical in explaining the discrepancy
      with oculomotor research.

PMID- 20039025
TI  - Combining multisensory temporal information for movement synchronisation.
AB  - The ability to synchronise actions with environmental events is a fundamental
      skill supporting a variety of group activities. In such situations, multiple
      sensory cues are usually available for synchronisation, yet previous studies have
      suggested that auditory cues dominate those from other modalities. We examine the
      control of rhythmic action on the basis of auditory and haptic cues and show that
      performance is sensitive to both sources of information for synchronisation.
      Participants were required to tap the dominant hand index finger in synchrony
      with a metronome defined by periodic auditory tones, imposed movements of the non
      dominant index finger, or both cues together. Synchronisation was least variable
      with the bimodal metronome as predicted by a maximum likelihood estimation (MLE)
      model. However, increases in timing variability of the auditory cue resulted in
      some departures from the MLE model. Our findings indicate the need for further
      investigation of the MLE account of the integration of multisensory signals in
      the temporal control of action.

PMID- 20039026
TI  - Quantifying the importance of high frequency components on the amplitude of
      physiological tremor.
AB  - The objective of this study was to determine the importance of every frequency
      component on total physiological tremor (PT) amplitude. We suspect that since
      high frequencies of PT are of lower amplitude in displacement, removing them will
      have little to no impact on PT amplitude. PT of the index finger was measured
      with a laser displacement sensor while the finger was held horizontally.
      Amplitude of tremor was calculated in displacement, velocity and acceleration. PT
      amplitude was also calculated within five frequency bands. Although displacement
      amplitude of oscillations within the 7.5-12.5 and 16.5-30 Hz frequency bands
      represent 24 and 10% of total PT oscillation amplitude, respectively, their
      removal reduced PT amplitude by less than 3%. Conversely, the removal of the
      oscillations within 1-3.5 Hz band from the PT signal reduced the amplitude of the
      original PT signal by 56% in displacement. This suggests that when a task to be
      studied involves the measurement of a reduction in tremor, focus should be on the
      oscillations in the 1-3.5 Hz band.

PMID- 20039027
TI  - Parabrachial nucleus neuronal responses to off-vertical axis rotation in
      macaques.
AB  - The caudal aspect of the parabrachial nucleus (PBN) contains neurons responsive
      to whole body, periodic rotational stimulation in alert monkeys (Balaban et al.
      in J Neurophysiol 88:3175-3193, 2002). This study characterizes the angular and
      linear motion-sensitive response properties of PBN unit responses during off
      vertical axis rotation (OVAR) and position trapezoid stimulation. The OVAR
      responses displayed a constant firing component which varied from the firing rate
      at rest. Nearly two-thirds of the units also modulated their discharges with
      respect to head orientation (re: gravity) during constant velocity OVAR
      stimulation. The modulated response magnitudes were equal during ipsilateral and
      contralateral OVARs, indicative of a one-dimensional accelerometer. These
      response orientations during OVAR divided the units into three spatially tuned
      populations, with peak modulation responses centered in the ipsilateral ear down,
      contralateral anterior semicircular canal down, and occiput down orientations.
      Because the orientation of the OVAR modulation response was opposite in polarity
      to the orientation of the static tilt component of responses to position
      trapezoids for the majority of units, the linear acceleration responses were
      divided into colinear dynamic linear and static tilt components. The orientations
      of these unit responses formed two distinct population response axes: (1) units
      with an interaural linear response axis and (2) units with an ipsilateral
      anterior semicircular canal-contralateral posterior semicircular canal plane
      linear response axis. The angular rotation sensitivity of these units is in a
      head-vertical plane that either contains the linear acceleration response axis or
      is perpendicular to the linear acceleration axis. Hence, these units behave like
      head-based ('strapdown') inertial guidance sensors. Because the PBN contributes
      to sensory and interoceptive processing, it is suggested that vestibulo-recipient
      caudal PBN units may detect potentially dangerous anomalies in control of
      postural stability during locomotion. In particular, these signals may contribute
      to the range of affective and emotional responses that include panic associated
      with falling, malaise associated with motion sickness and mal-de-debarquement,
      and comorbid balance and anxiety disorders.

PMID- 20039028
TI  - Development of visual control in stepping down.
AB  - Stepping down at a change of height is a fundamental part of human locomotion. At
      a novel step, this requires the transformation of visual information about a
      depth change into a stepping movement of appropriate size. However, little is
      known about this process or its development. We studied adults, 3- and 4-year-old
      children stepping down a single stair of variable height. We assessed how well
      stepping down was scaled to stair height using several kinematic measures. Of
      these, 'kneedrop' and 'toedrop' describe how far the leg has descended by the
      time it begins to 'swing in' in preparation for landing; and 'toeheight
      (speedpeak)' describes where the toe begins to decelerate. If visually
      controlled, their values should scale to the height of the stair. Under normal
      visual conditions, children scaled these movements to stair height as well as
      adults. In a second condition, participants closed their eyes just before
      stepping down to remove visual feedback during the step. Adults' steps were
      barely affected. For 4-year olds, only toeheight (speedpeak) decreased. For 3
      year olds, both toedrop and toeheight (speedpeak) scaled less well to stair
      height than normal. The results suggest that visuomotor processes for fine-tuned
      stepping control develop remarkably early, but are initially dependent on visual
      feedback.

PMID- 20039029
TI  - How many motoric body representations can we grasp?
AB  - At present there is a debate on the number of body representations in the brain.
      The most commonly used dichotomy is based on the body image, thought to underlie
      perception and proven to be susceptible to bodily illusions, versus the body
      schema, hypothesized to guide actions and so far proven to be robust against
      bodily illusions. In this rubber hand illusion study we investigated the
      susceptibility of the body schema by manipulating the amount of stimulation on
      the rubber hand and the participant's hand, adjusting the postural configuration
      of the hand, and investigating a grasping rather than a pointing response.
      Observed results showed for the first time altered grasping responses as a
      consequence of the grip aperture of the rubber hand. This illusion-sensitive
      motor response challenges one of the foundations on which the dichotomy is based,
      and addresses the importance of illusion induction versus type of response when
      investigating body representations.

PMID- 20039030
TI  - Persistent left superior vena cava resulting in left-to-right shunt.
AB  - We present an infant with unusual anatomy and physiology of a persistent left
      superior vena cava (LSVC). The adverse physiologic consequences of the LSVC were
      corrected with percutaneous placement of vascular plugs.

PMID- 20039032
TI  - QT dispersion in familial dysautonomia: study by Nussinovitch et al.

PMID- 20039031
TI  - Transcriptional regulation of heart valve progenitor cells.
AB  - The development and normal function of the heart valves requires complex
      interactions among signaling molecules, transcription factors and structural
      proteins that are tightly regulated in time and space. Here we review the roles
      of critical transcription factors that are required for specific aspects of
      normal valve development. The early progenitors of the heart valves are localized
      in endocardial cushions that express transcription factors characteristic of
      mesenchyme, including Twist1, Tbx20, Msx1 and Msx2. As the valve leaflets mature,
      they are composed of complex stratified extracellular matrix proteins that are
      regulated by the transcriptional functions of NFATc1, Sox9, and Scleraxis. Each
      of these factors has analogous functions in differentiation of related connective
      tissue lineages. Together, the precise timing and localized functions of specific
      transcription factors control cell proliferation, differentiation, elongation,
      and remodeling processes that are necessary for normal valve structure and
      function. In addition, there is increasing evidence that these same transcription
      factors contribute to congenital, as well as degenerative, valve disease.

PMID- 20039034
TI  - Saccharomyces cerevisiae CCMI 885 secretes peptides that inhibit the growth of
      some non-Saccharomyces wine-related strains.
AB  - The nature of the toxic compounds produced by Saccharomyces cerevisiae CCMI 885
      that induce the early death of Hanseniaspora guilliermondii during mixed
      fermentations, as well as their ability to inhibit the growth of other non
      Saccharomyces wine-related strains, was investigated. The killing effect of mixed
      supernatants towards H. guilliermondii was inactivated by protease treatments,
      thus revealing the proteinaceous nature of the toxic compounds. Analysis of the
      protein pattern of mixed supernatants on Tricine SDS-PAGE showed that this S.
      cerevisiae strain secretes peptides (<10 kDa), which were detected only when
      death of H. guilliermondii was already established. Death-inducing supernatants
      were ultrafiltrated by 10 and 2 kDa membranes, respectively, and the inhibitory
      effect of those permeates were tested in H. guilliermondii cultures. Results
      indicated that the (2-10) kDa protein fraction of those supernatants seemed to
      contain antimicrobial peptides active against H. guilliermondii. Thus, the (2-10)
      kDa protein fraction was concentrated and its inhibitory effect tested against
      strains of Kluyveromyces marxianus, Kluyveromyces thermotolerans, Torulaspora
      delbrueckii and H. guilliermondii. Under the growth conditions used for these
      tests, the (2-10) kDa protein fraction of S. cerevisiae CCMI 885 supernatants
      exhibited a fungistatic effect against all the strains and a fungicidal effect
      against K. marxianus.

PMID- 20039033
TI  - Tissue-tissue interactions during morphogenesis of the outflow tract.
AB  - The heart forms as a linear heart tube that loops and septates to produce a
      mature four-chambered structure. The single vessel emerging from the embryonic
      heart, the truncus arteriosus, divides into the aorta and the pulmonary artery as
      part of this septation process, and a series of additional morphogenetic events
      result in the proper alignment and orientation of the cardiac outflow tract.
      Recent evidence indicates that this process involves the complex interactions of
      multiple cell types including primary and secondary heart fields, neural crest,
      pharyngeal mesenchyme, endoderm, and endothelium. Among the many signals that
      mediate tissue-tissue interactions during the formation of the outflow tract, we
      have focused on the role of the Notch signaling pathway. Here, we focus on recent
      advances in our understanding of Notch-mediated regulation of cardiac development
      with specific attention to the formation of the cardiac outflow tract.

PMID- 20039035
TI  - Light/electricity conversion by a self-organized photosynthetic biofilm in a
      single-chamber reactor.
AB  - Biological energy-conversion systems are attractive in terms of their self
      sustaining and self-organizing nature and are expected to be applied to low-cost
      and environment-friendly processes. Here we show a biofilm-based
      light/electricity-conversion system that was self-organized from a natural
      microbial community. A bioreactor equipped with an air cathode and graphite-felt
      anode was inoculated with a green hot-spring microbial mat. When the reactor was
      irradiated with light, electric current was generated between the anode and
      cathode in accordance with the formation of green biofilm on the anode.
      Fluorescence microscopy of the green biofilm revealed the presence of chlorophyll
      containing microbes of approximately 10 microm in size, and these cells were
      abundant close to the surface of the biofilm. The biofilm community was also
      analyzed by sequencing of polymerase chain reaction-amplified small-subunit rRNA
      gene fragments, showing that sequence types affiliated with Chlorophyta,
      Betaproteobacteria, and Bacteroidetes were abundantly detected. These results
      suggest that green algae and heterotrophic bacteria cooperatively converted light
      energy into electricity.

PMID- 20039036
TI  - Biochemical features of microbial keratinases and their production and
      applications.
AB  - Keratinases are exciting proteolytic enzymes that display the capability to
      degrade the insoluble protein keratin. These enzymes are produced by diverse
      microorganisms belonging to the Eucarya, Bacteria, and Archea domains.
      Keratinases display a great diversity in their biochemical and biophysical
      properties. Most keratinases are optimally active at neutral to alkaline pH and
      40-60 degrees Celsius, but examples of microbial keratinolysis at alkalophilic
      and thermophilic conditions have been well documented. Several keratinases have
      been associated to the subtilisin family of serine-type proteases by analysis of
      their protein sequences. Studies with specific substrates and inhibitors
      indicated that keratinases are often serine or metalloproteases with preference
      for hydrophobic and aromatic residues at the P1 position. Keratinolytic enzymes
      have several current and potential applications in agroindustrial,
      pharmaceutical, and biomedical fields. Their use in biomass conversion into
      biofuels may address the increasing concern on energy conservation and recycling.

PMID- 20039037
TI  - A novel xyloglucan-specific endo-beta-1,4-glucanase: biochemical properties and
      inhibition studies.
AB  - A novel xyloglucan-specific endo-beta-1,4-glucanase gene (xeg5A) was isolated,
      cloned, and expressed in Esherichia coli. The enzyme XEG5A consisted of a C
      terminal catalytic domain and N-terminal sequence of approximately 90 amino acid
      residues with unknown function. The catalytic domain assumed an (alpha/beta)(8)
      fold typical of glycoside hydrolase (GH) family 5, with the two catalytic
      residues Glu240 and Glu362 located on opposite sides of the surface groove of the
      molecule. The recombinant enzyme showed high specificity towards tamarind
      xyloglucan and decreasing activity towards xyloglucan oligosaccharide (HDP-XGO),
      carboxymethyl cellulose, and lichenan. Tamarind xyloglucan was hydrolyzed to
      three major fragments, XXXG, XXLG/XLXG, and XLLG. The hydrolysis followed the
      Michaelis-Menten kinetics, yielding K (m) and V (max) of 3.61 +/- 0.23 mg/ml and
      0.30 +/- 0.01 mg/ml/min, respectively. However, the hydrolysis of HDP-XGO showed
      a decrease in the rate at high concentrations suggesting appearance of excess
      substrate inhibition. The addition of XXXG resulted in linear noncompetitive
      inhibition on the hydrolysis of tamarind xyloglucan giving a K (i) of 1.46 +/-
      0.13 mM. The enzyme was devoid of transglycosylase activities.

PMID- 20039038
TI  - Reconstruction after wide resection of the entire distal fibula in malignant bone
      tumours.
AB  - In this study we present a series of patients (n = 11) with resection of the
      entire distal fibula in the case of sarcoma or metastasis. Moreover, we describe
      a new method to restore ankle stability with a tibiotalocalcaneal arthrodesis
      using a retrograde hindfoot nail (n = 4) in contrast to tibiotalar arthrodesis
      with screws (n = 5). The screw fixation failed in two patients due to osteopoenic
      bone. The crucial benefits of an arthrodesis with a retrograde nail are a stable
      arthrodesis, intramedullary stabilisation of the tibia and avoidance of extrinsic
      material in the wound area. An arthrodesis with a retrograde nail is a good
      alternative for reconstruction after a wide distal fibula resection. The
      additional arthrodesis of the subtalar joint was not associated with worse
      functional results in the MSTS and TESS scores.

PMID- 20039039
TI  - Fenestration of aortic dissection using a fluoroscopy-based needle re-entry
      catheter system.

PMID- 20039040
TI  - A phase I trial of lomeguatrib and irinotecan in metastatic colorectal cancer.
AB  - BACKGROUND: Expression of the DNA repair protein O (6)-methylguanine-DNA
      methyltransferase (MGMT) correlates with resistance to irinotecan in colorectal
      cancer cell lines. This phase I study evaluated the maximum tolerated dose (MTD)
      of lomeguatrib, an inactivating pseudosubstrate of MGMT, in combination with
      irinotecan in patients with metastatic colorectal cancer and assessed the safety,
      toxicity and clinical pharmacology of combination treatment. PATIENTS AND
      METHODS: Patients with metastatic colorectal cancer received lomeguatrib (10-80
      mg PO) on days 1-5 with irinotecan (250-350 mg/m(2) IV) on day 4 of a 21-day
      cycle. RESULTS: Twenty-four patients, pre-treated with a median of 2 lines of
      chemotherapy, received 104 cycles of treatment. The MTD was defined as 80 mg/day
      lomeguatrib with 300 mg/m(2) irinotecan. The main toxicities observed were
      neutropaenia and diarrhoea. Lomeguatrib of 80 mg/day produced complete MGMT
      depletion in all available peripheral blood mononuclear cells (PBMCs) and paired
      tumour biopsies (one patient). There was no pharmacokinetic interaction between
      the drugs. In 22 patients assessable for tumour response, one achieved a partial
      response and 16 had stable disease. CONCLUSION: This study defined a tolerable
      dose of irinotecan in combination with lomeguatrib in patients with metastatic
      colorectal cancer. Combination treatment gave a similar response rate to
      irinotecan monotherapy in this heavily pre-treated patient group.

PMID- 20039041
TI  - The time to extinction for a stochastic SIS-household-epidemic model.
AB  - We analyse a Markovian SIS epidemic amongst a finite population partitioned into
      households. Since the population is finite, the epidemic will eventually go
      extinct, i.e., have no more infectives in the population. We study the effects of
      population size and within household transmission upon the time to extinction.
      This is done through two approximations. The first approximation is suitable for
      all levels of within household transmission and is based upon an Ornstein
      Uhlenbeck process approximation for the diseases fluctuations about an endemic
      level relying on a large population. The second approximation is suitable for
      high levels of within household transmission and approximates the number of
      infectious households by a simple homogeneously mixing SIS model with the
      households replaced by individuals. The analysis, supported by a simulation
      study, shows that the mean time to extinction is minimized by moderate levels of
      within household transmission.

PMID- 20039042
TI  - Sulfate metabolism in Tuber borchii: characterization of a putative sulfate
      transporter and the homocysteine synthase genes.
AB  - The homocysteine synthase (tbhos) and putative sulfate transporter (tbsul1) genes
      have been characterized in order to understand the sulfate metabolism and
      regulation in the ectomycorrhizal fungus Tuber borchii. The analyses of tbsul1
      and tbhos nucleotide and deduced amino acid sequences led to the identification
      of the typical domains shown in homologous proteins. Sulfate starvation condition
      upregulates both genes. The real-time PCR assay of tbsul1 revealed that gene
      expression was about threefold higher in mycelia grown under sulfate starvation
      for 2 days than in the mycelial control and in the same starvation condition, the
      sulfate uptake increased. Real-time PCR and enzymatic assays showed regulation of
      tbhos when sulfur sources were lacking, suggesting that a transcriptional
      regulation of this gene rather than a post-transcriptional one occurred.
      Furthermore, the tbsul1 and tbhos expression patterns were evaluated during the
      truffle life cycle, revealing an over-expression in the mature ascomata for both
      genes. In the ectomycorrhizal tissue, only tbhos was upregulated suggesting its
      substantial role in T. borchii cysteine synthesis. The regulation of tbsul1 and
      tbhos occurs primarily at the transcriptional level both during vegetative and
      fruiting phases and these genes could be directly involved in VOCs production.

PMID- 20039043
TI  - Mycotoxin Ochratoxin A-induced cell death and changes in oxidative metabolism of
      Arabidopsis thaliana.
AB  - We evaluated the phytotoxicity of mycotoxin ochratoxin A (OTA) from Aspergillus
      and Penicillium strains on Arabidopsis thaliana. The results demonstrate that the
      growth of Arabidopsis thaliana on media containing OTA was inhibited
      significantly. Moreover, OTA induced necrotic lesions in detached leaves, which
      are reminiscent of hypersensitive response lesions that are activated during
      plant-pathogen interactions and other abiotic stress factors. From our study, we
      can see that OTA exposure stimulated a biphasic oxidative burst in the leaves,
      resulting in the generation of hydrogen peroxide (H2O2) and superoxide anion
      radicals (O2(.-)) and in the concomitant down-regulation of antioxidant enzyme
      defense responses and up-regulation of lipid peroxidation. These results
      suggested that OTA damage might result from reactive oxygen species pathways. Our
      experiments provide a useful model plant system for research on OTA-induced plant
      cell death.

PMID- 20039044
TI  - Whole-genome scan identifies quantitative trait loci for chronic pastern
      dermatitis in German draft horses.
AB  - Chronic pastern dermatitis (CPD), also known as chronic progressive lymphedema
      (CPL), is a skin disease that affects draft horses. This disease causes painful
      lower-leg swelling, nodule formation, and skin ulceration, interfering with
      movement. The aim of this whole-genome scan was to identify quantitative trait
      loci (QTL) for CPD in German draft horses. We recorded clinical data for CPD in
      917 German draft horses and collected blood samples from these horses. Of these
      917 horses, 31 paternal half-sib families comprising 378 horses from the breeds
      Rhenish German, Schleswig, Saxon-Thuringian, and South German were chosen for
      genotyping. Each half-sib family was constituted by only one draft horse breed.
      Genotyping was done for 318 polymorphic microsatellites evenly distributed on all
      equine autosomes and the X chromosome with a mean distance of 7.5 Mb. An across
      breed multipoint linkage analysis revealed chromosome-wide significant QTL on
      horse chromosomes (ECA) 1, 9, 16, and 17. Analyses by breed confirmed the QTL on
      ECA1 in South German and the QTL on ECA9, 16, and 17 in Saxon-Thuringian draft
      horses. For the Rhenish German and Schleswig draft horses, additional QTL on ECA4
      and 10 and for the South German draft horses an additional QTL on ECA7 were
      found. This is the first whole-genome scan for CPD in draft horses and it is an
      important step toward the identification of candidate genes.

PMID- 20039045
TI  - Treatment and outcome of children with relapsed ependymoma: a multi-institutional
      retrospective analysis.
AB  - INTRODUCTION: More than a third of children with ependymoma experience relapse,
      and despite multimodal treatment, less than 25% of them can then achieve long
      term survival. Prognostic factors for patients who relapse have not been
      extensively analyzed. PATIENTS AND METHODS: We retrospectively analyzed 82
      patients from four pediatric oncology European institutions in order to identify
      prognostic factors and influence of treatment modalities in relapsed ependymoma.
      RESULTS: First relapse occurred after a median of 19 months (1 month-16 years).
      Five-year progression-free survival and overall survival of the cohort were 17%
      and 27.6%, respectively. Survival was statistically significantly higher for
      patients achieving gross total resection. No survival benefit was seen for
      children receiving chemotherapy whereas patients who were amenable to some form
      of re-irradiation had a better outcome. Objective responses were found in more
      than 25% of patients receiving oral etoposide, temozolomide, or
      vincristine/etoposide/cyclophosphamide regimens. Multivariate analysis confirmed
      that patients with mixed relapses, no surgery at relapse, and receiving
      chemotherapy did worse (hazard ratio = 3.6, 3.3, and 1.7, respectively, all p <
      0.05). DISCUSSION: Relapsed ependymoma carries a very poor prognosis with an
      indolent chronic course, leading to death in approximately 90% of the patients.
      Complete surgical resection whenever possible should be encouraged. Radiation
      therapy of the relapsed lesions can provide some minor benefit whereas
      chemotherapy despite the occasional responses provides no benefit in the final
      outcome which is dismal. Efforts have to be orchestrated internationally to
      enroll these patients on clinical trials using biology-based therapies.

PMID- 20039046
TI  - p38 MAPK-regulated EGFR internalization takes place in keratinocyte monolayer
      during stress conditions.
AB  - The epidermis is the outermost protection of the organism. As so, defence program
      has to be initiated in stress situation in order to protect keratinocytes. The
      EGF receptor (EGFR) controls cell proliferation and migration in keratinocytes,
      being a major regulator of keratinocyte homeostasis within the epidermis. The
      EGFR is known to be internalized without addition of ligand under the control of
      p38 MAPK during stress conditions in HeLa cells, but also following lipid rafts
      disruption in keratinocytes. This could represent an alternative internalization
      process that removes the EGFR from cell surface. Here, we investigated whether
      other stress conditions such as scratch wounding keratinocyte monolayer or
      incubation with a sensitizer chemical (i.e. DNFB), could also induce this
      peculiar mechanism of EGFR internalization. Our results show that both stressing
      conditions induce p38 MAPK activation concomitantly with EGFR internalization,
      independently of ligand binding to the EGFR. Inhibition of p38 MAPK activity
      during scratch wound blocks EGFR internalization at the margin of the wound while
      cell migration is impeded. Our results show thus that the p38 MAPK-dependent EGFR
      internalization is a process shared by keratinocytes when submitted to
      challenging conditions.

PMID- 20039047
TI  - Non-traumatic rupture of the left upper urinary tract during pregnancy without
      discernable underlying disorders.

PMID- 20039048
TI  - Complications in pregnancy after bariatric surgery.
AB  - INTRODUCTION: The application of bariatric surgery has recently spread among
      obese women including women of reproductive age. MATERIALS AND METHODS: We sought
      to present three cases of obese women undergoing bariatric surgery, their
      monitoring and complications during pregnancy. CONCLUSION: We suggest that
      conception should be postponed for at least 18 months after bariatric operation
      to avoid complications concerning both mother and fetus mainly associated with
      nutritional deficiencies due to the anatomical and physiological changes of such
      operations.

PMID- 20039049
TI  - Bipolar vessel sealing increases operative safety in laparoscopic-assisted
      vaginal hysterectomy.
AB  - BACKGROUND: To compare laparoscopic-assisted vaginal hysterectomy (LAVH) with and
      without bipolar vessel sealing (BVS) using the LigaSureTM device by meanings of
      intra- and postoperative course. METHODS: In a retrospective case-control study
      362 female patients (mean age 54.3 +/- 9.5 years) were included who underwent
      LAVH with (n = 252) and without (n = 110) use of BVS. Intra- and postoperative
      courses and adverse events were evaluated. RESULTS: A shorter mean operating time
      was found for LAVH with the use of BVS (65.28 +/- 16.33 min) when compared with
      LAVH without the use of BVS (83.73 +/- 21.53 min, P < 0.005). The mean
      postoperative stay did not differ significantly between the two groups (P >
      0.05); 15 out of 251 (6.0%) patients were found to have adverse events during or
      after LAVH with the use of BVS in contrast to 16 out of 110 (14.5%) patients
      during or after LAVH without the use of BVS (P < 0.05). Following the use of BVS
      significantly less patients reported postoperative pain for more than 7 days
      after the operation in contrast to the use of sutures (0/251 [0%] vs. 3/110
      [2.7%], respectively, P < 0.05). CONCLUSION: The use of LigaSureTM is effective
      in decreasing operating time, the overall complication rate and postoperative
      pain.

PMID- 20039050
TI  - A new calculation on spectrum of direct DNA damage induced by low-energy
      electrons.
AB  - In this work, direct DNA damage induced by low-energy electrons (<5 keV) is
      simulated using Monte Carlo methods, and the resulting yield of various strand
      breaks and base damages in cellular environment is presented. The simulation is
      based on a new inelastic cross section for the production of electron track
      structure in liquid water, and on ionization cross sections of DNA bases to
      generate base radical. Especially, a systematic approach of simulating detailed
      base damage is suggested. This approach includes improvement of a volume model of
      DNA, generation of the DNA base sequence, conversion of ionization events in
      liquid water at hit site to the ionization interaction of electrons with DNA
      bases and development of an algorithm to convert a base radical to a damage. The
      results obtained in terms of strand breaks are compared with those of experiments
      and other theoretical calculations, and good agreement was obtained. The yield of
      detailed base damages and clustered DNA damages caused by the combination of
      various strand breaks and base damages is presented, and the corresponding
      distribution characteristics are analyzed. The influence of the relative content
      of base pairs A-T and G-C in a DNA segment on the yield of both strand breaks and
      base damages is also explored. The present work provides fundamental information
      on DNA damage and represents the first effort toward the goal of obtaining the
      spectrum of clustered DNA damage including detailed base damages, for the
      mechanistic interpretation and prediction of radiation effects.

PMID- 20039051
TI  - Hybrid computational phantoms for medical dose reconstruction.
AB  - As outlined in NCRP Report No. 160 of the US National Council on Radiation
      Protection and Measurements (NCRP), the average value of the effective dose to
      exposed individuals in the United States has increased by a factor of 1.7 over
      the time period 1982-2006, with the contribution of medical exposures
      correspondingly increasing by a factor of 5.7. At present, medical contributors
      to effective dose include computed tomography (50% of total medical exposure),
      nuclear medicine (25%), interventional fluoroscopy (15%), and conventional
      radiography and diagnostic fluoroscopy (10%). An increased awareness of medical
      exposures has led to a gradual shift in the focus of radiation epidemiological
      studies from traditional occupational and environmental exposures to those
      focusing on cohorts of medical patients exposed to both diagnostic and
      therapeutic sources. The assignment of organ doses to patients in either a
      retrospective or a prospective study has increasingly relied on the use of
      computational anatomic phantoms. In this paper, we review the various methods and
      approaches used to construct patient models to include anthropometric databases,
      cadaver imaging, prospective volunteer imaging studies, and retrospective image
      reviews. Phantom format types--stylized, voxel, and hybrid--as well as phantom
      morphometric categories--reference, patient-dependent, and patient-specific--are
      next defined and discussed. Specific emphasis is given to hybrid phantoms-those
      defined through the use of combinations of polygon mesh and non-uniform rational
      B-spline (NURBS) surfaces. The concept of a patient-dependent phantom is
      reviewed, in which phantoms of non-50th percentile heights and weights are
      designed from population-based morphometric databases and provided as a larger
      library of phantoms for patient matching and lookup of refined values of organ
      dose coefficients and/or radionuclide S values. We close with two brief examples
      of the use of hybrid phantoms in medical dose reconstruction--diagnostic nuclear
      medicine for pediatric subjects and interventional fluoroscopy for adult
      patients.

PMID- 20039052
TI  - Pulmonary arteriovenous malformation causing sudden death due to spontaneous
      hemothorax.
AB  - A sudden death due to hemothorax caused by spontaneous rupture of a congenital
      pulmonary arteriovenous malformation (AVM) is reported. A 44-year-old woman died
      unexpectedly with chest pain and dyspnea. The post-mortem examination revealed a
      massive right-sided hemothorax arising from a subpleural AVM of the upper lobe.
      There were multiple telangiectases in the tongue and the tonsils, as typically
      associated with Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia,
      HHT). The post-mortem molecular genetic analysis proved the presence of a disease
      causing mutation in the endoglin gene constituting a predisposition for pulmonary
      AVMs. According to the literature, almost half of the AVMs in the lung are seen
      in HHT patients. Based on the presented case and the relevant literature, the
      article addresses the forensic aspects of fatal hemothorax and the importance of
      detecting the source of bleeding.

PMID- 20039053
TI  - Characterization of endocytic compartments after holo-high density lipoprotein
      particle uptake in HepG2 cells.
AB  - Holo-high density lipoprotein (HDL) particle uptake, besides selective lipid
      uptake, constitutes an alternative pathway to regulate cellular cholesterol
      homeostasis. In the current study, the cellular path of holo-HDL particles was
      investigated in human liver carcinoma cells (HepG2) using combined light and
      electron microscopical methods. The apolipoprotein moiety of HDL was visualized
      with different markers: horseradish peroxidase, colloidal gold and the
      fluorochrome Alexa(568), used in fluorescence microscopy and after photooxidation
      correlatively at the ultrastructural level. Time course experiments showed a
      rapid uptake of holo-HDL particles, an accumulation in endosomal compartments,
      with a plateau after 1-2 h of continuous uptake, and a clearance 1-2 h upon
      replacement by unlabeled HDL. Correlative microscopy, using HDL-Alexa(568)-driven
      diaminobenzidine (DAB) photooxidation, identified the fluorescent organelles as
      DAB-positive multivesicular bodies (MVBs) in the electron microscope; their
      luminal contents but not the internal vesicles were stained. Labeled MVBs
      increased in numbers and changed shapes along with the duration of uptake, from
      polymorphic organelles with multiple surface domains and differently shaped
      protrusions dominating at early times of uptake to compact bodies with mainly
      tubular appendices and densely packed vesicles after later times. Differently
      shaped and labeled surface domains and appendices, as revealed by three
      dimensional reconstructions, as well as images of homotypic fusions indicate the
      dynamics of the HDL-positive MVBs. Double staining visualized by confocal
      microscopy, along with the electron microscopic data, shows that holo-HDL
      particles after temporal storage in MVBs are only to a minor degree transported
      to lysosomes, which suggests that different mechanisms are involved in cellular
      HDL clearance, including resecretion.

PMID- 20039055
TI  - Elderly oarsmen have larger trunk and thigh muscles and greater strength than age
      matched untrained men.
AB  - To evaluate whether regularly performed rowing exercise affects the trunk muscles
      size and function, and to examine the effect of rowing exercise on thigh muscle
      size and function in elderly rowers, we compared the cross-sectional area (CSA)
      and strength of these muscles in elderly male rowers and in age-matched untrained
      men. Participants were 16 elderly rowing-trained men (ROW age, 67.8 +/- 2.3
      years) and 18 elderly untrained men (CON 66.2 +/- 3.0 years). CSA was measured by
      MRI in the trunk and thigh muscles. Isometric trunk flexion force and leg
      extension power were measured. ROW had a 20% larger total trunk muscle CSA than
      CON (P < 0.01); rectus abdominis was 27% larger, psoas major 64% larger, and
      erector spinae 14% larger in ROW than in CON (P < 0.05-0.001). Isometric trunk
      flexion force was related to the CSA of the rectus abdominis (r = 0.777, P <
      0.001) and psoas major (r = 0.694, P < 0.001), and was 42% larger in ROW than in
      CON (P < 0.001). However, force adjusted for the CSA of the muscles did not
      differ significantly between CON and ROW. In ROW, the CSA was 13% larger in the
      total thigh muscles (P < 0.01), and leg extension power was 43% higher than in
      CON (P < 0.001). These results suggest that rowing exercise is a favorable
      training modality for the trunk muscles, especially psoas major and that it
      improves thigh muscle size and function in elderly men.

PMID- 20039054
TI  - Neuromuscular control adaptations in elite athletes: the case of top level
      karateka.
AB  - This paper aimed at investigating the neuromuscular response of knee flexor and
      extensor muscles in elite karateka and karate amateurs (Amateurs) during
      isokinetic knee flexion/extensions and during the execution of a front kick (FK).
      Surface electromyograms (sEMG) were recorded from the right vastus lateralis (VL)
      and biceps femoris (BF) muscles with a four-array electrode during maximal
      isometric knee flexion and extension (maximal voluntary contraction), during
      isokinetic contractions (30 degrees , 90 degrees , 180 degrees , 270 degrees ,
      340 degrees , 400 degrees /s), and during the FK. The level of VL and BF agonist
      (ago) and antagonist (ant) activation during the isokinetic and FK protocols was
      quantified through normalized sEMG root mean square value (%RMS(ago/ant
      ISOK/FK)). VL and BF average muscle fiber conduction velocity (CV) was computed
      for isokinetic and FK. Isokinetic flexion and extension torques and knee angular
      velocity during FK were also assessed. Analysis of variance was used to test the
      effect of group, angular velocity, and task on the assessed variables (P < 0.05).
      Elite karateka showed higher isokinetic knee flexion torque when compared with
      Amateurs. For all angular velocities, VL and BF %RMS(ant-isokinetic) were lower
      in elite karateka, while their BF-CV(isokinetic) BF-CV(front kick) and BF
      %RMS(ant-front kick) values were higher. For VL and BF, %RMS(ago-front kick) was
      lower than %RMS(ago-isokinetic) in both groups. Elite karateka demonstrated a
      typical neuromuscular activation strategy that seems task and skill level
      dependent. Knee flexion torque and CV results suggest the presence of an improved
      ability of elite karateka to recruit fast MUs as a part of training induced
      neuromuscular adaptation.

PMID- 20039056
TI  - The effect of 48 weeks of aerobic exercise training on cutaneous vasodilator
      function in post-menopausal females.
AB  - Skin blood flow (SkBF) and endothelial-dependent vasodilatation decline with
      ageing and can be reversed with exercise training. We tested whether 48 weeks of
      training could improve SkBF and endothelial function in post-menopausal females;
      20 post-menopausal subjects completed the study. SkBF was measured by laser
      Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as
      LDF/blood pressure. Resting CVC was measured at 32 degrees C and peak CVC at 42
      degrees C. Cutaneous endothelial-dependent and -independent vasodilatations were
      determined by the iontophoresis of acetylcholine (ACh) and sodium nitroprusside
      (SNP), respectively. All assessments described were performed at entry (week 0),
      and after 6, 12, 24, 36, and 48 weeks of training. Resting CVC measures did not
      change (P > 0.05) throughout the study. Peak CVC increased (P < 0.05) after 24
      weeks (7.2 +/- 1.2 vs. 11.6 +/- 1.4 AU mmHg(-1)) and at the 36- and 48-week
      assessments (13.0 +/- 1.7 and 14.9 +/- 2.1 AU mmHg(-1), respectively). Responses
      to ACh also increased (P < 0.05) at the 24-week assessment (5.1 +/- 2.1 vs. 8.55
      +/- 2.3 AU mmHg(-1)) and increased further at the 36 and 48-week assessments
      (11.6 +/- 3.7 and 13.2 +/- 3.9 AU mmHg(-1), respectively). Cutaneous responses to
      SNP increased (P < 0.05) after 36 weeks (8.7 +/- 2.1 vs. 13.02 +/- 2.23 AU mmHg(
      1) at 36 weeks). VO(2max) increased after 12 weeks (23.5 +/- 0.7 vs. 25.4 +/- 0.9
      ml kg(-1) min(-1)) and improved (P < 0.05) further throughout the study (31.6 +/-
      1.8 ml kg(-1) min(-1) at week 48). Aerobic exercise produces positive adaptations
      in the cutaneous vasodilator function to local heating as well as in cutaneous
      endothelial and endothelial-independent vasodilator mechanisms. Aerobic capacity
      was also significantly improved. These adaptations were further enhanced with
      progressive increases in exercise intensity.

PMID- 20039057
TI  - Muscle adaptations and performance enhancements of soccer training for untrained
      men.
AB  - We examined the physical demands of small-sided soccer games in untrained middle
      age males and muscle adaptations and performance effects over 12 weeks of
      recreational soccer training in comparison with continuous running. Thirty-eight
      healthy subjects (20-43 years) were randomized into a soccer (SO), running (RU)
      and control (CO) group. Two-three weekly 1-h training sessions were performed.
      Muscle lactate (30.1 +/- 4.1 vs. 15.6 +/- 3.3 mmol/kg d.w.), blood lactate, blood
      glucose and time above 90% HR(max) (20 +/- 4% vs. 1 +/- 1%) were higher (p <
      0.05) during training in SO than in RU. After 12 weeks of training, quadriceps
      muscle mass and mean muscle fibre area were 9 and 15% larger (p < 0.05) in SO,
      but unaltered in RU, and in SO, the fraction of FTx fibres was lowered (10.7 +/-
      1.8 vs. 17.9 +/- 3.2%). In SO, citrate synthase activity was 10 and 14% higher (p
      < 0.05) after 4 and 12 weeks, but unaltered in RU. After 4 weeks VO(2max) and Yo
      Yo IE2 performance were elevated (p < 0.05) to a similar extent in SO (7 and 37%)
      and RU (6 and 36%) but increased further (p < 0.05) from 4 to 12 weeks in SO (6
      and 23%). In SO, 30-m sprint performance was improved (p < 0.05) by 0.11 +/- 0.02
      s. Blood lactate during running at 11 km/h was lowered (p < 0.05) from 0 to 4 and
      4 to 12 weeks (2.6 +/- 0.3 vs. 3.8 +/- 0.6 vs. 6.1 +/- 0.9 mM) and from 0 to 12
      weeks in RU. No changes occurred for CO. In conclusion, recreational soccer
      organized as small-sided games stimulates both aerobic and anaerobic energy
      turnover and is an effective type of training leading to significant
      cardiovascular and muscular adaptations as well as performance enhancements
      throughout a 12-week training period.

PMID- 20039058
TI  - Unfolding an electronic integrate-and-fire circuit.
AB  - Many physical and biological phenomena involve accumulation and discharge
      processes that can occur on significantly different time scales. Models of these
      processes have contributed to understand excitability self-sustained oscillations
      and synchronization in arrays of oscillators. Integrate-and-fire (I+F) models are
      popular minimal fill-and-flush mathematical models. They are used in neuroscience
      to study spiking and phase locking in single neuron membranes, large scale neural
      networks, and in a variety of applications in physics and electrical engineering.
      We show here how the classical first-order I+F model fits into the theory of
      nonlinear oscillators of van der Pol type by demonstrating that a particular
      second-order oscillator having small parameters converges in a singular
      perturbation limit to the I+F model. In this sense, our study provides a novel
      unfolding of such models and it identifies a constructible electronic circuit
      that is closely related to I+F.

PMID- 20039059
TI  - As Tribolium matures as a model insect, Coleopteran Community Congregates in
      Cologne.

PMID- 20039060
TI  - Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow
      separate molecular pathways.
AB  - With the aim to provide more insight into their biology, a series of 79
      liposarcomas (LS) representative of all main subtypes was analysed for
      chromosomal imbalances using comparative genomic hybridization. Based on the
      genetic data, unsupervised hierarchical clustering unveiled two main LS clusters,
      each with two subclusters, one comprising three subsets. The first main cluster
      consisted of one larger subcluster, being characterised by gains/high-level
      amplifications of chromosomal subregions 12q13-q15, and exclusively included well
      differentiated and dedifferentiated LS. A smaller subcluster was set apart on the
      basis of recurrent gains of 20q13 and 8q24, and mainly comprised pleomorphic and
      myxoid/round cell LS. The larger subcluster was subdivided into three subsets,
      one with nearly exclusive overrepresentations of 12q13-q15, the second with
      additional frequent gains of 1q21-q24, and the third with further recurrent
      overrepresentations of 6q22-q24, 20q13, and 12q24 and frequent losses of 13q14
      q21 and 11q22-q23. While the first subset comprised both well-differentiated and
      dedifferentiated LS, the second and third subsets entirely included
      dedifferentiated LS. The second main cluster was characterised by recurrent
      overrepresentations of 5p13-p15, 1q21-q24, 1p12-p21, and 17p11.2-p12 and
      essentially comprised pleomorphic and myxoid/round cell LS. A separation of this
      second main cluster into two subclusters was based on additional gains on 22q13
      and losses on 1q42-q43. Genomic profiling reveals genetically distinct subsets of
      dedifferentiated LS, which are clearly different from pleomorphic, myxoid/round
      cell, and, for some subsets, from well-differentiated LS. These data indicate
      that dedifferentiated LS follow separate tumourigenic pathways and that genetic
      analysis is important to unravel these differences.

PMID- 20039061
TI  - Late-onset adenosine deaminase deficiency presenting with Heck's disease.
AB  - Focal epithelial hyperplasia, also known as Heck's disease, is a rare but
      distinctive entity of viral etiology with characteristic clinical and
      histopathological features. It is a benign, asymptomatic disease of the oral
      mucosa caused by human papilloma viruses (HPV). Previous studies postulated an
      association between these lesions and immunodeficiency. Genetic deficiency of
      adenosine deaminase (ADA) results in varying degrees of immunodeficiency,
      including neonatal onset severe combined immunodeficiency (ADA-SCID), and milder,
      later onset immunodeficiency. We report a 12-year-old girl with the late onset
      ADA deficiency presenting with Heck's disease. Our case report should draw
      attention to the possibility of immunodeficiency in patients with HPV-induced
      focal epithelial hyperplasia.

PMID- 20039062
TI  - Munchausen syndrome by proxy mimicking as Gaucher disease.
AB  - Although rare, Munchausen syndrome by proxy (MBP) is a potentially life
      threatening form of child abuse. Here, we report a 19-month-old female infant who
      presented with hepatosplenomegaly, anemia, thrombocytopenia, and recurrent
      septicemia. She was initially thought to have myelodysplastic syndrome. Further
      hematological and immunological investigations revealed no cause. beta
      Glucosylceramidase enzyme activity on dried blood spot was suggestive of Gaucher
      disease. However, the enzyme level on cultured skin fibroblast was not consistent
      with Gaucher disease. The first hint about MBP was the recurrent sepsis with
      numerous gram negative rods. Furthermore, the mother's behavior and health
      history raised our suspicion about MBP. The child showed significant improvement
      after she was separated from the mother for a week. Finally, the mother confessed
      that she was spitting in local herbs and injecting it into the central line. This
      is, to our knowledge, the first report of MBP resembling in its presentation
      Gaucher disease. This case should alert the general and specialized pediatricians
      about MBP, as it may mimic metabolic diseases like Gaucher disease.

PMID- 20039063
TI  - Effects of measured susceptibility genes on cancer risk in family studies.
AB  - Numerous family studies have been performed to assess the associations between
      cancer incidence and genetic and non-genetic risk factors and to quantitatively
      evaluate the cancer risk attributable to these factors. However, mathematical
      models that account for a measured hereditary susceptibility gene have not been
      fully explored in family studies. In this report, we proposed statistical
      approaches to precisely model a measured susceptibility gene fitted to family
      data and simultaneously determine the combined effects of individual risk factors
      and their interactions. Our approaches are structured for age-specific risk
      models based on Cox proportional hazards regression methods. They are useful for
      analyses of families and extended pedigrees in which measured risk genotypes are
      segregated within the family and are robust even when the genotypes are available
      only in some members of a family. We exemplified these methods by analyzing six
      extended pedigrees ascertained through soft-tissue sarcoma patients with p53 germ
      line mutations. Our analyses showed that germ-line p53 mutations and sex had
      significant interaction effects on cancer risk. Our proposed methods in family
      studies are accurate and robust for assessing age-specific cancer risk
      attributable to a measured hereditary susceptibility gene, providing valuable
      inferences for genetic counseling and clinical management.

PMID- 20039064
TI  - Preserving the rectus muscle during laparoscopically harvesting an omental flap.

PMID- 20039065
TI  - The impact of obesity on outcomes of laparoscopic surgery for colorectal cancer
      in Asians.
AB  - BACKGROUND: The influence of obesity on surgical outcomes after laparoscopic
      colorectal surgery in Asian patients is unclear. The aim of this study was to
      evaluate the feasibility and safety of laparoscopic surgery in obese Asian
      patients with colorectal cancer. METHODS: We retrospectively reviewed the
      prospectively collected data on 984 consecutive patients who underwent
      laparoscopic surgery for colorectal cancer between May 2001 and February 2008.
      Patients were classified according to the categories proposed by the
      International Obesity Task Force, as Nonobese (body mass index [BMI] < 25.0
      kg/m(2)), Obese I (BMI 25.0-29.9 kg/m(2)), and Obese II (BMI > or = 30 kg/m(2)).
      Surgical outcomes, including open conversion, operation time, postoperative
      complications, estimated blood loss, and postoperative hospital stay, were
      compared in Nonobese, Obese I, and Obese II patients. RESULTS: Of the 984
      patients, 645 (65.5%), 312 (31.7%), and 27 (2.7%), were classified as Nonobese,
      Obese I, and Obese II, respectively. Clinicopathologic characteristics were
      similar among the three groups. The Obese II group had higher conversion rates
      (14.8% versus 2.6% and 2.9%, P = 0.001), longer operation time (258 versus 201
      and 215 min, P = 0.001), and longer postoperative hospital stay (12.1 versus 9.5
      and 9.2 days, P = 0.035) than the Nonobese and Obese I groups. However, the rates
      of intraoperative events (P = 0.634) and postoperative complications (P = 0.603)
      were similar in nonobese and obese patients. Independent risk factors for
      conversion were BMI group and operation type. Obese II patients had an 8.36-fold
      greater risk of conversion than had Nonobese patients (P = 0.001). CONCLUSIONS:
      With sufficient experience, laparoscopic colorectal surgery in obese Asian
      patients is feasible and safe, offering all the benefits of a minimally invasive
      approach. Management of Asian colorectal cancer patients with BMI > or = 30
      kg/m(2) requires meticulous perioperative care, and colorectal surgeons must be
      familiar with obesity-related challenges in such patients.

PMID- 20039066
TI  - Recommended timing for surveillance ultrasonography to diagnose portal splenic
      vein thrombosis after laparoscopic splenectomy.
AB  - BACKGROUND: Symptomatic portal or splenic vein thrombosis (PSVT) is a rare but
      potentially lethal complication of laparoscopic splenectomy (LS). While routine
      postoperative duplex ultrasound surveillance can be used for early detection, the
      optimal timing is unknown. The aim of this study is to investigate the incidence
      and progression of asymptomatic PSVT 1 week and 1 month after LS. METHODS:
      Consecutive patients scheduled for LS for hematologic disease participated in
      this study. Patients underwent surveillance for PSVT using duplex ultrasonography
      1 week and 1 month postoperatively. RESULTS: 43 of 48 patients planning to
      undergo LS in the study period were enrolled, with 3 subsequently excluded,
      leaving 40 for further analysis. The indications for LS were benign disease in 31
      [19 had immune thrombocytopenia purpura (ITP)] and malignant disease in 9. A hand
      assisted technique was used in 12 cases. PSVT was diagnosed in 9/40 patients
      (22.5%). Seven (77.8%) were diagnosed by 1 week with ultrasound, of whom one had
      mild symptoms (fever and diarrhea). After anticoagulation, subsequent ultrasounds
      showed resolution or improvement in all seven patients. Thirty-three patients had
      a normal ultrasound result at 1 week. One of these patients also had a computed
      tomography (CT) scan that found a PSVT not seen on ultrasound. Twenty-seven
      patients returned for follow-up after normal 1-week imaging: 26 patients had an
      ultrasound at 1 month, with no new PSVT found. One additional patient did not
      return for subsequent ultrasound until 2 months later, when a new distal SVT was
      found; ultrasound at 6 months showed complete resolution without treatment.
      CONCLUSION: The 1-week incidence of PSVT after LS was 8/40 (20%). The high
      incidence justifies ultrasonographic screening on postoperative day 7. If
      asymptomatic PSVT has not developed at this time, it is unlikely to develop by 1
      month, and subsequent screening ultrasound at 1 month is not required.

PMID- 20039067
TI  - Gasless balloon laparoscopy.
AB  - BACKGROUND: The concept of balloon laparoscopy (B-LSC) pursues the simplification
      of conventional diagnostic laparoscopy (LSC). The pneumoperitoneum is replaced by
      a transparent balloon, which is positioned in front of the optical system. It
      shall be shown that with this arrangement diagnostic LSC can be performed outside
      of the operating room without requiring general anesthesia. METHODS: An
      inflatable balloon was developed for a 30 degrees /3.5-mm rod lens. Intra
      abdominally the balloon was expanded to a diameter of 30 mm by air insufflation,
      and B-LSC was performed. Twelve patients were examined in general anesthesia
      before laparoscopic surgery. Twelve patients were subjected to B-LSC fully awake
      or with sedation (midazolam or propofol/S-ketamine) as a "second-look" procedure
      by way of a flexible trocar (port) left in the abdominal wall at the end of
      previous operation. Eight patients have been first provided with a trocar under
      sedation (midazolam or propofol/S-ketamine) combined with local anesthesia, and B
      LSC was performed before laparoscopic surgery. RESULTS: On a scale of 1-5, the
      general impression was rated 1.9, the navigability to the different abdominal
      organs 2.5, the resolution 1.5, the stability of the system optic/trocar 2.1, the
      suitability of the balloon format 1.9, and the stability of the balloon against
      lateral shear forces 2.4. The degree of painfulness of the examination was rated
      2.8, the tolerance of the port 1.4, and the degree of painfulness of trocar
      placement at 2.5. On a scale of 1 to 3, the strain of the abdominal musculature
      was rated 1.4 and the obstruction by adhesions 1.7. DISCUSSION: B-LSC is
      technically practicable with good imaging qualities and without requiring
      pneumoperitoneum. It is tolerated in great extent under slight sedation and
      particularly well under deep sedation. The procedure is suitable for diagnostics
      of unclear abdominal conditions, as a second-look LSC and also as a staging LSC.

PMID- 20039068
TI  - Multipurpose surgical robot as a laparoscope assistant.
AB  - BACKGROUND: This study demonstrates the effectiveness of a new, compact surgical
      robot at improving laparoscope guidance. Currently, the assistant guiding the
      laparoscope camera tends to be less experienced and requires physical and verbal
      direction from the surgeon. Human guidance has disadvantages of fatigue and
      shakiness leading to inconsistency in the field of view. This study investigates
      whether replacing the assistant with a compact robot can improve the stability of
      the surgeon's field of view and also reduce crowding at the operating table.
      METHODS: A compact robot based on a bevel-geared "spherical mechanism" with 4
      degrees of freedom and capable of full dexterity through a 15-mm port was
      designed and built. The robot was mounted on the standard railing of the
      operating table and used to manipulate a laparoscope through a supraumbilical
      port in a porcine model via a joystick controlled externally by a surgeon. The
      process was videotaped externally via digital video recorder and internally via
      laparoscope. Robot position data were also recorded within the robot's motion
      control software. RESULTS: The robot effectively manipulated the laparoscope in
      all directions to provide a clear and consistent view of liver, small intestine,
      and spleen. Its range of motion was commensurate with typical motions executed by
      a human assistant and was well controlled with the joystick. CONCLUSIONS:
      Qualitative analysis of the video suggested that this method of laparoscope
      guidance provides highly stable imaging during laparoscopic surgery, which was
      confirmed by robot position data. Because the robot was table-mounted and compact
      in design, it increased standing room around the operation table and did not
      interfere with the workspace of other surgical instruments. The study results
      also suggest that this robotic method may be combined with flexible endoscopes
      for highly dexterous visualization with more degrees of freedom.

PMID- 20039069
TI  - Intracorporeal stapled anastomosis following laparoscopic segmental gastrectomy
      for gastric cancer: technical report and surgical outcomes.
AB  - BACKGROUND: Limited gastrectomy for early gastric body cancers can offer a better
      functional outcome by preserving more remnant stomach. Intracorporeal stapled
      techniques result in cosmesis and avoid awkward anastomosis through a
      minilaparotomy. METHODS: Laparoscopic segmental gastrectomy is indicated for
      early gastric cancers of the body of the stomach with no evidence of lymph node
      involvement. Laparoscopic pylorus-preserving gastrectomy is a specific type of
      segmental resection for lower-body lesions with dissection of lymph nodes in
      station 6. Intracorporeal gastrogastric anastomosis is performed by the delta
      shaped technique using linear staplers. RESULTS: Since January 2008 we have
      performed 12 laparoscopic pylorus-preserving gastrectomies and 13 laparoscopic
      segmental gastrectomies. All procedures were completed by laparoscopy. One
      patient with minor anastomotic leakage was managed conservatively. Bleeding from
      the anastomosis was not encountered in any of the patients. One patient developed
      narrowing at the anastomotic site and was treated successfully by balloon
      dilatation. There was no stasis encountered in any of the patients. CONCLUSIONS:
      Laparoscopic segmental gastrectomy with acceptable surgical outcomes is
      technically feasible. Although the impact of such resections on oncological
      outcomes remains to be further evaluated, laparoscopic segmental gastrectomy
      represents a minimally invasive limited resection that maximizes the potential
      for a better quality of life following gastric cancer surgery.

PMID- 20039070
TI  - Society of American Gastrointestinal and Endoscopic Surgeons(SAGES)statement on
      the relationship between professional medical associations and industry.

PMID- 20039071
TI  - Evaluation of a modified circular stapler for use as a viscerotomy formation and
      closure device in natural orifice surgery.
AB  - BACKGROUND: The most challenging of the many hurdles surgeons must overcome to
      perform natural orifice translumenal endoscopic surgery (NOTES) safely is
      viscerotomy closure. The perfect device must be easy to deploy, suitable for use
      on any viscera, and able to create a rapid, reliable, and durable closure. The
      authors developed a novel device based on an existing circular stapler platform
      to create and then subsequently close a viscerotomy. The device was tested
      initially on an ex vivo porcine stomach model, then used on a survival canine
      model to confirm adequacy of gastric closure and rapidity of deployment. METHODS:
      Three study arms, each containing five stomachs, were used. For the experimental
      arm, a Surgassist (PMI, Langhorne, PA, USA) powered circular stapler (EEA)
      modified with an auger tip and premounted endoloops was used. This novel device
      was compared with two gold standard closure techniques: hand-sewn two-layer
      closure and linear stapled closure. Each stomach then was inflated slowly with
      dye, and the pressure at which each closure leaked was recorded. For evaluation
      of the closure's durability and ease of use, five mongrel dogs undergoing
      transgastric intraabdominal surgery had their gastrotomy formed and closed using
      the modified Surgassist stapler. Each animal was survived 14 days, then killed,
      after which a necropsy was performed. RESULTS: In the ex vivo model, the modified
      PMI EEA consistently achieved burst pressures exceeding 260 mmHg, which was
      statistically significant compared with either the hand-sewn closure or the
      linear stapled closure. In the survival group, all the animals survived for the 2
      week study period without signs of sepsis. At necropsy, the closures were found
      to be intact. CONCLUSION: The prototype transvisceral purse-string device
      consistently produced a tight, safe, and reliable closure. It can be deployed and
      cinch-closed rapidly. This study suggests that this new device may be a promising
      option for use in NOTES.

PMID- 20039072
TI  - Laparoscopic incisional hernia repair is feasible and safe after liver
      transplantation.
AB  - BACKGROUND: Incisional hernia is a common complication after liver
      transplantation. The current study evaluated incidence and risk factors for
      incisional hernia and compared laparoscopic and open hernia repair in terms of
      feasibility and outcome. METHODS: A cohort of 225 patients was prospectively
      investigated. The median follow-up period was 61 months (range, 6-186 months).
      The study cohort had 31 patients who underwent open repair and 13 who underwent
      laparoscopic repair. RESULTS: Incisional hernia, found in 57 patients (25%), had
      occurred after a median of 17 months (range, 5-138 months). The significant risk
      factors were male gender (p = 0.001) and body mass index (BMI) greater than 25
      kg/m(2) (p = 0.002). A trend toward a lower recurrence rate (15% vs 35%; p =
      0.28) and fewer surgical complications (15% vs 19%; p = 0.99) was found in the
      laparoscopic group. CONCLUSIONS: Incisional hernia is a frequent complication
      after liver transplantation. Associated risk factors are male gender and a BMI
      greater than 25 kg/m(2). Laparoscopic hernia repair for such patients is feasible
      and safe.

PMID- 20039073
TI  - Single-port laparoscopic cholecystectomy: initial experience.
AB  - BACKGROUND: As surgeons embrace the concept of increasingly less invasive
      surgery, techniques using only a single small incision have begun to gain
      traction. Several commercially available products have emerged recently. The
      TriPort system and the SILS Port are single-port devices that allow the surgeon
      to perform laparoscopic surgery through a 2- to 3-cm periumbilical incision. This
      study aimed to ascertain whether these devices allow safe and reliable access for
      laparoscopic cholecystectomy. METHODS: From March 2008 to June 2009, single-port
      laparoscopic cholecystectomy was attempted for 22 patients with an average age of
      40 years (range, 23-73 years). The data collected prospectively after
      institutional review board approval included demographics, operative time,
      complications, and reasons for conversion to standard four-port laparoscopic
      surgery. RESULTS: The operation was completed successfully for 21 of the 22
      patients (15 women and 7 men) using five different techniques. The mean body mass
      index (BMI) of the patients was 32.7 kg/cm(2) (range, 22.3-46.1 kg/cm(2)). Three
      of the patients had previously undergone laparoscopic Roux-en-Y gastric bypass.
      The mean operative time was 80.8 min (range, 51-156 min). One patient experienced
      a Richter's hernia postoperatively, which required a reoperation and subsequent
      bowel resection. One patient required conversion to a standard four-port
      laparoscopic cholecystectomy because the articulating instrument could not reach
      the gallbladder from the umbilicus. CONCLUSION: The results from the current
      series show single-port laparoscopic cholecystectomy to be a promising technique.
      A variety of patient demographics appear suited to this approach. The operative
      time in this series compares favorably with that for the standard four-port
      operation. The feasibility of single-port laparoscopic cholecystectomy is now
      established. However, routine application of this novel technique requires an
      evaluation of its safety and cost effectiveness in larger studies. In addition,
      its superiority over standard laparoscopic cholecystectomy in terms of
      postoperative pain, cosmesis, and overall patient satisfaction requires further
      study. Refinements in instrumentation will enable wider use of this novel
      minimally invasive approach.

PMID- 20039074
TI  - Standardized phase angle from bioelectrical impedance analysis as prognostic
      factor for survival in patients with cancer.
AB  - PURPOSE: Phase angle (PA), determined by bioelectrical impedance analysis (BIA),
      has been considered as a prognostic factor in several clinical conditions. The
      purpose of this study is to investigate PA, after adjusting for sex and age
      (standardized phase angle; SPA) as a prognostic factor for survival in cancer
      patients. METHODS: A prospective study was conducted in 195 patients before the
      first chemotherapy course. BIA was performed in all patients and SPA was
      calculated. The Kaplan-Meier method was used to calculate survival. The Cox
      regression method was used to evaluate the independent prognostic effect of PA
      after adjustment for other variables. RESULTS: Patients with SPA < -1.65 had a
      smaller survival rate than those with SPA >= -1.65 (p < 0.001). Using Cox
      regression, the mortality rate was higher in patients with SPA < -1.65 (RR 3.12
      CI: 2.03-4.79; p < 0.001). After multivariate analysis, patients with PA < -1.65
      still presented a higher mortality rate (RR 2.35 CI: 1.41-3.90; p = 0.001).
      CONCLUSIONS: The present study demonstrates that PA, used as SPA, is an
      independent prognostic indicator in this group of cancer patients receiving
      chemotherapy treatment even after adjustment for other prognostic variables.

PMID- 20039076
TI  - Retrospective analysis of predictors of cerebral vasospasm after ruptured
      cerebral aneurysm surgery: influence of the location of subarachnoid blood.
AB  - PURPOSE: The amount of blood on computed tomography (CT) has been shown to be a
      predictor of cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the
      influence of the location of the blood on the incidence of vasospasm remains
      unclear. We retrospectively assessed the association of the blood volumes in the
      individual components (cisterns and fissures) of CT scans with angiographic
      vasospasm after SAH. METHODS: One hundred forty-nine SAH patients scheduled for
      cerebral aneurysm clipping were enrolled. The amount of subarachnoid blood was
      classified using the Fisher CT grade. The amounts of subarachnoid blood in 5
      cisterns or 3 fissures were also evaluated using SAH scores ranging from 0 to 3
      (0, no blood; 3, completely filled with blood). Cerebral vasospasm was diagnosed
      by the results of angiography. RESULTS: Angiographic vasospasm developed in 51 of
      149 patients (34%). Of those, 26 patients were symptomatic. The Fisher CT grade
      and SAH scores in the right and left sylvian fissures and suprasellar cisterns
      were significantly higher in patients with angiographic vasospasm than in those
      without it. Univariate logistic regression analysis revealed that a high Fisher
      CT grade and high SAH scores in the right and left sylvian fissures and
      suprasellar cisterns were predictors of angiographic vasospasm. Multivariate
      analysis indicated that the SAH score in the right sylvian fissure was an
      independent predictor of angiographic vasospasm (odds ratio, 3.6; 95% confidence
      interval (CI), 1.7-7.7; P = 0.01). CONCLUSION: The results indicated that the
      amount of blood in the right sylvian fissure was significantly associated with
      the development of angiographic vasospasm after SAH.

PMID- 20039075
TI  - Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy
      in cardiac surgery.
AB  - Antifibrinolytic agents have been prophylactically administered to patients
      undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to
      plasmin-mediated coagulation disturbances. After the recent market withdrawal of
      aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon
      aminocaproic acid and tranexamic acid are currently available for clinical use.
      Although the use of aprotinin recently raised major concerns about postoperative
      thrombosis and organ dysfunctions, there is a paucity of information on the
      potential complications related to lysine analogs. Using the available
      preclinical and clinical data, we present current perspectives on the hemostatic
      mechanism and potential harms of antifbirnolytic therapy related to cardiac
      surgery. Fibrin formation is the critical step for hemostasis at the site of
      vascular injury, and localized fibrinolytic activity counterbalances excess
      fibrin formation which might result in vascular occlusion. Inhibition of the
      endogenous fibrinolytic system may be associated with thrombotic complications in
      susceptible organs. It is thus important to understand CPB-related changes in
      endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA),
      plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).

PMID- 20039077
TI  - Landiolol, an ultra short acting beta1-blocker, improves pulmonary edema after
      cardiopulmonary resuscitation with epinephrine in rats.
AB  - PURPOSE: Epinephrine is frequently administered as an essential drug for
      cardiopulmonary resuscitation (CPR) in clinical situations. Unfortunately,
      epinephrine elicits unfavorable effects, for example pulmonary edema, both during
      and after CPR. We hypothesized that administration of landiolol during CPR with
      epinephrine would reduce the degree of pulmonary edema and improve survival.
      Therefore using a rat CPR model, we investigated the effect of landiolol with
      epinephrine on pulmonary and cardiac injury following CPR. METHODS: Twelve male
      Sprague-Dawley rats were allocated to Group-E (Gr.-E: 0.02 mg/kg epinephrine) and
      thirteen animals to Group-EL (Gr.-EL: 0.02 mg/kg epinephrine with 0.5 mg/kg
      landiolol). After tracheotomy, cardiac arrest was induced by obstructing the
      endotracheal tube. We measured the lung wet-to-dry (W/D) weight ratio to evaluate
      the degree of pulmonary edema 2 h after CPR. The hematocrit (Hct) difference
      between before and after CPR (Hct-D) was calculated. We measured the plasma
      levels of troponin-I (T-I) to evaluate the degree of cardiac injury. RESULTS: The
      lung W/D weight ratio in Gr.-E (6.4 +/- 1.06, mean +/- SD) was significantly
      higher than that for Gr.-EL (4.9 +/- 0.80, p < 0.01). Hct-D was significantly
      higher in Gr.-E (10.2 +/- 3.1%) than in Gr.-EL (5.2 +/- 3.5%, p < 0.01). We
      observed no difference in survival or difference of T-I. (Gr.-E: 2.62 +/- 0.51
      ng/ml, Gr.-EL: 3.43 +/- 2.72 ng/ml). CONCLUSION: Administration of landiolol
      during CPR with epinephrine prevented the development of pulmonary edema and the
      increase in Hct during and after CPR.

PMID- 20039078
TI  - Ketamine eliminates propofol pain but does not affect hemodynamics during
      induction with double-lumen tubes.
AB  - BACKGROUND AND OBJECTIVE: Propofol injection during induction of anesthesia
      induces pain. Ketamine has been shown to reduce the injection pain. However,
      ketamine has unfavorable adverse effects, including increased secretion
      production and hemodynamic responses, which might induce pulmonary or hemodynamic
      adverse events, especially in patients undergoing lung surgery who require a
      double-lumen tube (DLT). The aim of this study was to determine whether ketamine
      can safely reduce propofol injection pain during induction of anesthesia for lung
      surgery. METHODS: Forty-five patients scheduled for elective lung surgery
      requiring DLT were randomly allocated into three groups. Patients received saline
      (control), ketamine 0.5 mg kg(-1) (0.5 ketamine), or ketamine 1.0 mg kg(-1) (1.0
      ketamine), followed by 5 ml propofol 30 s later. An anesthesiologist blinded to
      the study group assessed pain score during induction, hemodynamics during DLT
      placement, and secretion production during anesthetic management. RESULTS:
      Pretreatment of 0.5 mg kg(-1) ketamine reduced the incidence and intensity of
      propofol injection pain, whereas 1.0 mg kg(-1) ketamine completely eliminated the
      pain. There were no significant differences regarding oxygenation during one-lung
      ventilation (OLV) and hemodynamics during induction among the three groups,
      although ketamine increased secretion production. CONCLUSIONS: One milligram per
      kilogram of ketamine completely eliminated pain associated with propofol
      injection without affecting hemodynamics during induction of anesthesia and
      oxygenation during OLV.

PMID- 20039079
TI  - The intravenous anesthetic propofol inhibits lipopolysaccharide-induced hypoxia
      inducible factor 1 activation and suppresses the glucose metabolism in
      macrophages.
AB  - PURPOSE: Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor of
      hypoxia-induced gene expression. Anesthetics and perioperative drugs have been
      reported to affect HIF-1 activity. However, the effect of propofol on HIF-1
      activity is not well documented. In this study, we investigated the effect of
      propofol on HIF-1 activation using macrophage-differentiated THP-1 cells.
      METHODS: Cells were exposed to lipopolysaccharide (LPS) under 20 or 1% O(2)
      conditions with or without propofol treatment. The cell lysate was subjected to
      Western blot analysis using anti-HIF-1alpha and HIF-1beta antibodies. HIF-1
      dependent gene expression was investigated by quantitative real-time reverse
      transcriptase PCR analysis and luciferase assay. The amount of cellular lactate
      and ATP was assayed. RESULTS: Propofol suppressed HIF-1alpha protein accumulation
      induced by LPS, but not by hypoxia in the THP-1 cells in a dose-dependent manner
      by inhibiting the neo-synthesis of HIF-1alpha protein. Induction of the HIF-1
      downstream gene expression including glucose transporter 1, enolase 1, lactate
      dehydrogenase A, pyruvate dehydrogenase kinase-1 and vascular endothelial growth
      factor was inhibited by propofol. Propofol suppressed LPS-induced lactate
      accumulation and ATP content in THP-1 cells. CONCLUSION: Our experimental results
      indicate that propofol inhibits HIF-1 activation and downstream gene expression
      induced by LPS and suppressed HIF-1-dependent glucose metabolic reprogramming.
      HIF-1 suppression by propofol in macrophages may explain molecular mechanisms
      behind the inhibitory effect of propofol on cellular inflammatory responses.

PMID- 20039080
TI  - Airtraq optical laryngoscope: initial clinical experience in 20 children.

PMID- 20039081
TI  - Displacement of the epiglottis during intubation with the Pentax-AWS Airway
      Scope.
AB  - The Pentax-AWS system is a rigid indirect video laryngoscope with integrated tube
      guidance. Complications associated with this device are not well understood. We
      report two cases of epiglottis malposition during intubation with the Pentax-AWS.
      The standard technique of using the Pentax-AWS system involves direct elevation
      of the epiglottis for exposure of the vocal cords. The blade tip should be passed
      posterior to the epiglottis for laryngeal exposure, but pressure on the anterior
      surface of the epiglottis by the tip can rarely happen even during the correct
      maneuver. Although the Pentax-AWS provides clear images of the airway structures,
      it is sometimes difficult to observe the epiglottis continuously because the
      camera is located beneath the blade tip. Consequently, the view of the epiglottis
      from the camera may be impeded by the blade tip and may result in undiagnosed
      epiglottis malposition. The AWS's structural feature and its approach to the
      larynx can be associated with increased chance of unexpected epiglottis folding.
      It is particularly important to confirm normal position of the epiglottis during
      withdrawal of the device to prevent this complication.

PMID- 20039082
TI  - Conversion of atrial flutter to sinus rhythm during landiolol infusion.
AB  - A 73-year-old male patient with a past history of hypertension and atrial
      premature contraction underwent endoscopic restoration of the left bubonocele.
      Sinus rhythm was confirmed by preoperative electrocardiography, but paroxysmal
      atrial flutter developed when abdominoscopy was started. Continuous
      administration of landiolol hydrochloride at a dose of 0.005 mg kg(-1) min(-1)
      after a loading dose of 0.04 mg kg(-1) min(-1) for 1 min resulted in control of
      heart rate without a decrease in blood pressure. Atrial flutter was converted to
      sinus rhythm 3 min after the start of administration. Landiolol hydrochloride was
      administered continuously until the morning of the following day and sinus rhythm
      was maintained postoperatively.

PMID- 20039083
TI  - Methods to monitor distribution and metabolic activity of mesenchymal stem cells
      following in vivo injection into nucleotomized porcine intervertebral discs.
AB  - Intervertebral disc (IVD) degeneration involves a series of biochemical and
      morphological changes leading to loss of spinal stability and flexibility. Cell
      therapy is promising to reconstitute IVDs with new cells, however, sustained
      metabolic activity seems crucial for an active contribution to regeneration. The
      aim of the present study was to establish methods for separate follow up of
      persistence and activity of autologous porcine mesenchymal stem cells (pMSC)
      after implantation into IVDs of Goettingen minipigs in vivo in order to conclude
      about the potential of such an intervention strategy. For quantitative follow up,
      the transfer matrix was supplemented with Al(2)O(3) particles and pMSC which were
      retrovirally labeled with firefly luciferase (pMSC-Luc). Six mature Goettingen
      minipigs underwent matrix based cell transfer after partial nucleotomy of lumbar
      IVDs (n = 24). Day 0 and day 3 segments were analyzed for retained volume of
      Al(2)O(3) particles by micro-computed-tomography (muCT) and for cell activity by
      luciferase enzyme assessment. Three days after injection a reduction of Al(2)O(3)
      particles (P = 0.028) to about 9% and of pMSC-Luc activity to about 7% of initial
      values (P = 0.003) was detected, which suggests loss of 90% of the implant
      material under in vivo conditions without evidence for reduced pMSC-Luc metabolic
      activity (P = 0.887). In conclusion, separate follow up of implant material and
      cell activity was possible and unravels problems with in vivo implant persistence
      after annular puncture rather than quick loss of cell activity. Therefore, IVD
      regeneration-strategies should increasingly focus on annulus reconstruction in
      order to reduce implant loss due to annular failure.

PMID- 20039085
TI  - An approach to the management of Amyand's hernia and presentation of an
      interesting case report.
AB  - INTRODUCTION: Inguinal hernia is one of the most common operations and 1% of the
      cases contain appendix in the hernial sac, which is known as Amyand's hernia.
      Inflamed appendix and its presence in recurrent inguinal hernia is a rare
      encounter in general surgery. The management of Amyand's hernia is not
      straightforward without awareness. METHODS: Recurrent inguinal hernia with
      Amyand's hernia history, clinical features and management was studied and
      compared with the present literature. We have discussed the management options
      and an approach using a Medline literature review. RESULTS: An 80-year-old
      gentleman who had a right-side inguinal hernia operated 40 years ago presented
      with a right groin swelling and increasing redness associated with pain for 3
      days. Clinical signs and symptoms were in favour of strangulated inguinal hernia.
      He was operated and appendicectomy was done for inflamed non-perforated
      appendicitis. Prolene mesh repair was done and he was treated with a full course
      of antibiotics. DISCUSSION: Amyand's hernia is difficult to diagnose pre
      operatively and its presence in recurrent hernia has only been reported once
      before. The management of Amyand's hernia is not straightforward in most of the
      cases. Inflamed and perforated appendix needs to be removed. Delayed mesh repair
      is a better surgical option in perforated appendix cases.

PMID- 20039084
TI  - Review of metastatic spine tumour classification and indications for surgery: the
      consensus statement of the Global Spine Tumour Study Group.
AB  - Choosing the right operation for metastatic spinal tumours is often difficult,
      and depends on many factors, including life expectancy and the balance of the
      risk of surgery against the likelihood of improving quality of life. Several
      prognostic scores have been devised to help the clinician decide the most
      appropriate course of action, but there still remains controversy over how to
      choose the best option; more often the decision is influenced by habit, belief
      and subjective experience. The purpose of this article is to review the present
      systems available for classifying spinal metastases, how these classifications
      can be used to help surgical planning, discuss surgical outcomes, and make
      suggestions for future research. It is important for spinal surgeons to reach a
      consensus regarding the classification of spinal metastases and surgical
      strategies. The authors of this article constitute the Global Spine Tumour Study
      Group: an international group of spinal surgeons who are dedicated to studying
      the techniques and outcomes of surgery for spinal tumours, to build on the
      existing evidence base for the surgical treatment of spinal tumours.

PMID- 20039086
TI  - Hereditary spastic paraplegia and amyotrophy associated with a novel locus on
      chromosome 19.
AB  - We identified a family in Mali with two sisters affected by spastic paraplegia.
      In addition to spasticity and weakness of the lower limbs, the patients had
      marked atrophy of the distal upper extremities. Homozygosity mapping using single
      nucleotide polymorphism arrays showed that the sisters shared a region of
      extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls.
      These findings indicate a clinically and genetically distinct form of hereditary
      spastic paraplegia with amyotrophy, designated SPG43.

PMID- 20039087
TI  - Inhibition of protein deacetylation augments herpes simplex virus type 1
      activated transcription of host fucosyltransferase genes associated with virus
      induced sLex expression.
AB  - Herpes simplex virus type 1 induces expression of the selectin ligand sialyl
      Lewis X in infected cells by activating transcription of three normally silent
      host glycosyltransferase genes, FUT3, FUT5, and FUT6, a process that is initiated
      by binding of viral RNA to cellular protein kinase R. We investigated the
      involvement of protein deacetylation and promoter methylation in viral activation
      of host FUT genes by analysing the effects of appropriate inhibitors on the
      transcription rates of the FUT genes in virus-infected cells. The histone
      deacetylase inhibitor trichostatin A augmented the viral activation of FUT
      transcription, whereas inhibition of DNA methylation did not affect transcription
      of these genes. The trichostatin A enhancement did not involve interference with
      expression of viral late genes or viral DNA replication. Thus, the virus
      activated FUT genes are at least partially suppressed by deacetylation of
      histones or other regulatory proteins in uninfected HEL cells, whereas promoter
      methylation is a less important factor.

PMID- 20039089
TI  - Perceptual chunking in the self-produced songs of Bengalese finches (Lonchura
      striata var. domestica).
AB  - Like humans, songbirds, including Bengalese finches, have hierarchical structures
      in their vocalizations. When humans perceive a sentence, processing occurs in
      phrase units, not words. In this study, we investigated whether songbirds also
      perceive their songs by chunks (clusters of song notes) rather than single song
      notes. We trained male Bengalese finches to react to a short noise in a Go/NoGo
      task. We then superimposed the noise onto recordings of their own songs and
      examined whether the reaction time was affected by the location of the short
      noise, that is, whether the noise was placed between chunks or in the middle of a
      chunk. The subjects' reaction times to the noise in the middle of a chunk were
      significantly longer than those to the noise placed between chunks. This result
      was not observed, however, when the songs were played in reverse. We thus
      concluded that Bengalese finches perceive their songs by chunks rather than
      single notes.

PMID- 20039088
TI  - Number of and distance between response elements in Kaposi's sarcoma-associated
      herpesvirus ORF57 promoter influence its activation by replication and
      transcription activator and its repression by interferon regulatory factor 7.
AB  - Kaposi's sarcoma-associated herpesvirus ORF57 expression is highly responsive to
      replication and transcription activator (RTA) and interferon regulatory factor 7
      (IRF-7). Three RTA response elements (RREs) have been identified in the ORF57
      promoter. Here, we show evidence of another functional RRE located between nt
      82003 and 82081, which can complement the loss of RTA activation resulting from
      RRE1 deletion. Repeats of a recombination signal-binding protein Jkappa (RBP
      Jkappa) site enhanced RTA activation, which could not be suppressed by IRF-7.
      Alteration of the distance between the RBP-Jkappa site and RRE2 modulated
      responsiveness to RTA and IRF-7. These results will help to elucidate the precise
      regulation of viral gene expression.

PMID- 20039090
TI  - Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in
      respiratory tract infections outside of study conditions: a post-study survey.
AB  - All published evidence on procalcitonin (PCT)-guided antibiotic therapy was
      obtained in trials where physicians knew that they were being monitored, possibly
      resulting in higher adherence to the PCT algorithm. This study investigates the
      effectiveness of PCT guidance in an observational quality control survey. We
      monitored antibiotic therapy and algorithm adherence in consecutive patients with
      respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland,
      between May 2008 and February 2009. The results were compared to the site
      specific results of the former ProHOSP study. Overall and more pronounced for
      patients with community-acquired pneumonia, the median duration of antibiotic
      treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7
      days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics
      were administered according to the prespecified PCT algorithm. No significant
      differences concerning adverse medical outcome could be detected. This study
      mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of
      trial conditions. If algorithm adherence is reinforced, antibiotic exposure can
      be markedly reduced with subsequent reduction of antibiotic-associated side
      effects and antibiotic resistance. The integration of the PCT algorithm into
      daily practice requires ongoing reinforcement and involves a learning process of
      the prescribing physicians.

PMID- 20039091
TI  - A 3-D constrained mixture model for mechanically mediated vascular growth and
      remodeling.
AB  - In contrast to the widely applied approach to model soft tissue remodeling
      employing the concept of volumetric growth, microstructurally motivated models
      are capable of capturing many of the underlying mechanisms of growth and
      remodeling; i.e., the production, removal, and remodeling of individual
      constituents at different rates and to different extents. A 3-dimensional
      constrained mixture computational framework has been developed for vascular
      growth and remodeling, considering new, microstructurally motivated kinematics
      and constitutive equations and new stress and muscle activation mediated
      evolution equations. Our computational results for alterations in flow and
      pressure, using reasonable physiological values for rates of constituent growth
      and turnover, concur with findings in the literature. For example, for flow
      induced remodeling, our simulations predict that, although the wall shear stress
      is restored completely, the circumferential stress is not restored employing
      realistic physiological rate parameters. Also, our simulations predict different
      levels of thickening on inner versus outer wall locations, as shown in numerous
      reports of pressure-induced remodeling. Whereas the simulations are meant to be
      illustrative, they serve to highlight the experimental data currently lacking to
      fully quantify mechanically mediated adaptations in the vasculature.

PMID- 20039092
TI  - Mechano-regulation of mesenchymal stem cell differentiation and collagen
      organisation during skeletal tissue repair.
AB  - A number of mechano-regulation theories have been proposed that relate the
      differentiation pathway of mesenchymal stem cells (MSCs) to their local
      biomechanical environment. During spontaneous repair processes in skeletal
      tissues, the organisation of the extracellular matrix is a key determinant of its
      mechanical fitness. In this paper, we extend the mechano-regulation theory
      proposed by Prendergast et al. (J Biomech 30(6):539-548, 1997) to include the
      role of the mechanical environment on the collagen architecture in regenerating
      soft tissues. A large strain anisotropic poroelastic material model is used in a
      simulation of tissue differentiation in a fracture subject to cyclic bending
      (Cullinane et al. in J Orthop Res 20(3):579-586, 2002). The model predicts non
      union with cartilage and fibrous tissue formation in the defect. Predicted
      collagen fibre angles, as determined by the principal decomposition of strain-
      and stress-type tensors, are similar to the architecture seen in native articular
      cartilage and neoarthroses induced by bending of mid-femoral defects in rats.
      Both stress and strain-based remodelling stimuli successfully predicted the
      general patterns of collagen fibre organisation observed in vivo. This provides
      further evidence that collagen organisation during tissue differentiation is
      determined by the mechanical environment. It is envisioned that such predictive
      models can play a key role in optimising MSC-based skeletal repair therapies
      where recapitulation of the normal tissue architecture is critical to successful
      repair.

PMID- 20039093
TI  - Diversity in meiotic spindle origin and determination of cytokinetic planes in
      sporogenesis of complex thalloid liverworts (Marchantiopsida).
AB  - As the earliest divergent land plants, bryophytes (mosses, hornworts, and
      liverworts) provide insight into the evolution of the unique plant process of
      sporogenesis by which meiosis results in heavy walled spores. New
      immunohistochemical data on microtubules and gamma-tubulin in four genera of
      complex thalloid liverworts combined with previously published data on another
      four genera demonstrate grades in the evolution of spindle organization in
      meiosis. We have discovered that all recognized forms of microtubule organizing
      centers (MTOCs) in plant cells (plastid MTOCs, spheroid cytoplasmic MTOCs, polar
      organizers, and nuclear envelope MTOCs) occur in organization of the meiotic
      spindle of complex thalloid liverworts. In addition, all aspects of pre-meiotic
      preparation for quadripartitioning of the sporocyte into a tetrad of spores
      occur, with the exception of pre-meiotic wall precursors found in certain simple
      thalloids. The preparation includes morphogenetic plastid migration, cortical
      bands of microtubules that mark future cytokinetic planes in pre-meiosis,
      quadrilobing of the cytoplasm during meiotic prophase, and quadripolar
      microtubule systems that are transformed into functionally bipolar metaphase I
      spindles. Quadripolar spindle origin is typical of bryophyte sporogenesis even
      though the MTOCs involved may differ. However, in certain crown taxa of complex
      thalloids the spindle develops with no traces of quadripolarity and placement of
      intersporal walls is determined after meiosis, as is typical of higher plants.

PMID- 20039094
TI  - Helix insertion into bilayers and the evolution of membrane proteins.
AB  - Polytopic alpha-helical membrane proteins cannot spontaneously insert into lipid
      bilayers without assistance from polytopic alpha-helical membrane proteins that
      already reside in the membrane. This raises the question of how these proteins
      evolved. Our current knowledge of the insertion of alpha-helices into natural and
      model membranes is reviewed with the goal of gaining insight into the evolution
      of membrane proteins. Topics include: translocon-dependent membrane protein
      insertion, antibiotic peptides and proteins, in vitro insertion of membrane
      proteins, chaperone-mediated insertion of transmembrane helices, and C-terminal
      tail-anchored (TA) proteins. Analysis of the E. coli genome reveals several
      predicted C-terminal TA proteins that may be descendents of proteins involved in
      pre-cellular membrane protein insertion. Mechanisms of pre-translocon polytopic
      alpha-helical membrane protein insertion are discussed.

PMID- 20039096
TI  - The value of well-designed experiments in studying diseases with special
      reference to amphibians.
AB  - Relatively few studies of amphibian diseases have employed standard ecological
      experimental designs. We discuss what constitutes a well-designed ecological
      experiment and encourage their use in disease studies. We illustrate how well
      designed experiments can be used to determine the effects of pathogens on
      amphibians and we illustrate how ancillary information, including that collected
      using molecular tools, can be used to enhance the value of such experiments.

PMID- 20039095
TI  - The enhancement of antiproliferative and proapoptotic activity of HDAC inhibitors
      by curcumin is mediated by Hsp90 inhibition.
AB  - Curcumin, a natural polyphenol, has been described to exhibit effects on
      signaling pathways, leading to induction of apoptosis. In this study, we observed
      that curcumin inhibited Hsp90 activity causing depletion of client proteins
      implicated in survival pathways. Based on this observation, this study was
      designed to investigate the cellular effects of curcumin combination with the pan
      HDAC inhibitors, vorinostat and panobinostat, which induce hyperacetylation of
      Hsp90, resulting in inhibition of its chaperone function. The results showed
      that, at subtoxic concentrations, curcumin markedly sensitized tumor cells to
      vorinostat- and panobinostat-induced growth inhibition and apoptosis. The
      sensitization was associated with persistent depletion of Hsp90 client proteins
      (EGFR, Raf-1, Akt, and survivin). In conclusion, our findings document a novel
      mechanism of action of curcumin and support the therapeutic potential of
      curcumin/HDAC inhibitors combination, because the synergistic interaction was
      observed at pharmacologically achievable concentrations, which were ineffective
      when each drug was used alone.

PMID- 20039097
TI  - Impact of temperature variability on cholera incidence in southeastern Africa,
      1971-2006.
AB  - Africa has a number of climate-sensitive diseases. One that remains a threat to
      public health is cholera. The aquatic environment temperature is the most
      important ecological parameter governing the survival and growth of Vibrio
      cholerae. Indeed, recent studies indicate that global warming might create a
      favorable environment for V. cholerae and increase its incidence in vulnerable
      areas. In light of this, a Poisson Regression Model has been used to analyze the
      possible association between the cholera rates in southeastern Africa and the
      annual variability of air temperature and sea surface temperature (SST) at
      regional and hemispheric scales, for the period 1971-2006. The results showed a
      significant exponential increase of cholera rates in humans during the study
      period. In addition, it was found that the annual mean air temperature and SST at
      the local scale, as well as anomalies at hemispheric scales, had significant
      impact on the cholera incidence during the study period. Despite future
      uncertainty, the climate variability has to be considered in predicting further
      cholera outbreaks in Africa. This may help to promote better, more efficient
      preparedness.

PMID- 20039098
TI  - Preparation, characterisation and preliminary antitumour activity evaluation of a
      novel nanoparticulate system based on a cisplatin-hyaluronate complex and N
      trimethyl chitosan.
AB  - In this work, nanoparticles with a positive surface charge were prepared through
      the electrostatic interaction of a new cisplatin-hyaluronate complex with N
      trimethyl chitosan (substitution degree of 85%). Mean particle diameter was
      approximately 195 nm. Drug loading of nanoparticles, which had a zeta potential
      of about 27 mV, was equal to 6% w/w. After 24 h, while the cisplatin-hyaluronate
      complex released approximately 60% w/w drug in phosphate buffered saline at pH
      7.4, approximately 40% w/w of total cisplatin was released from nanoparticles.
      The same cumulative amounts of released drug were found after 48 h. These
      nanoparticles, as well as the starting cisplatin-hyaluronate complex, were active
      on all cell lines tested (P388, A2780, A549), with an antiproliferative activity
      similar to that of cisplatin. Apoptosis was markedly induced in A2780 cells by
      nanoparticles. In a preliminary in vivo experiment, the antitumour activity
      against a murine tumour (P388 cells) subcutaneously implanted in mice, resulted
      similar to that of cisplatin for nanoparticles whereas the starting complex
      showed a non-significant activity at the cisplatin dose tested. Body weight
      change of treated mice suggested a significantly better tolerance of the
      nanoparticles compared to cisplatin, after an initial brief period of acute
      toxicity higher than the parent drug. These results indicate that such a
      particulate system could be useful as a carrier for cisplatin delivery.

PMID- 20039099
TI  - Relationship between glucose catabolism and xanthan production in Xanthomonas
      oryzae pv. oryzae.
AB  - Two genes involved in central carbon metabolism were inactivated to modulate
      intracellular glucose 6-phosphate and to evaluate its effects on xanthan
      production in wild-type Xanthomonas oryzae pv. oryzae. Upon the inactivation of
      the phosphogluconate dehydratase gene (edd), intracellular glucose 6-phosphate
      increased from 0.05 to 1.17 mmol/g (dry cell wt). This was accompanied by
      increased xanthan production of up to 2.55 g/l (culture medium). In contrast,
      inactivation of 6-phosphogluconate dehydrogenase gene (gndA) did not influence
      intracellular glucose 6-phosphate nor xanthan production. The intracellular
      availability of glucose 6-phosphate is proposed as a rate-limiting factor in
      xanthan production, and it may be possible to increases production of xanthan by
      modulating the activities of enzymes in central carbon metabolism.

PMID- 20039100
TI  - Characterization of dipeptidylcarboxypeptidase of Leishmania donovani: a
      molecular model for structure based design of antileishmanials.
AB  - Leishmania donovani dipeptidylcarboxypeptidsae (LdDCP), an angiotensin converting
      enzyme (ACE) related metallopeptidase has been identified and characterized as a
      putative drug target for antileishmanial chemotherapy. The kinetic parameters for
      LdDCP with substrate, Hip-His-Leu were determined as, Km, 4 mM and Vmax, 1.173
      micromole/ml/min. Inhibition studies revealed that known ACE inhibitors
      (captopril and bradykinin potentiating peptide; BPP1) were weak inhibitors for
      LdDCP as compared to human testicular ACE (htACE) with Ki values of 35.8 nM and
      3.9 microM, respectively. Three dimensional model of LdDCP was generated based on
      crystal structure of Escherichia coli DCP (EcDCP) by means of comparative
      modeling and assessed using PROSAII, PROCHECK and WHATIF. Captopril docking with
      htACE, LdDCP and EcDCP and analysis of molecular electrostatic potentials (MEP)
      suggested that the active site domain of three enzymes has several minor but
      potentially important structural differences. These differences could be
      exploited for designing selective inhibitor of LdDCP thereby antileishmanial
      compounds either by denovo drug design or virtual screening of small molecule
      databases.

PMID- 20039101
TI  - A comparative study of AutoDock and PMF scoring performances, and SAR of 2
      substituted pyrazolotriazolopyrimidines and 4-substituted pyrazolopyrimidines as
      potent xanthine oxidase inhibitors.
AB  - 4-Alkylidenehydrazino-1H-pyrazolo[3,4-d]pyrimidines, 4-arylmethylidenehydrazino
      1H-pyrazolo[3,4-d]pyrimidines, and 2-substituted 7H-pyrazolo[4,3-e]-1,2,4
      triazolo-[1,5-c]-pyrimidines as potential xanthine oxidase inhibitors were docked
      into the active site of the bovine milk xanthine dehydrogenase using two scoring
      functions involved in AutoDock 3.05 and the CAChe 6.1.10. The correlation
      coefficiency obtained between the AutoDock binding energy and IC(50) of the
      inhibitors was better than that obtained by the CAChe-PMF docking score. Many
      ligands exhibited one to four hydrogen bonds within the active site, where the
      detected hydrogen bonds by CAChe was identified quantitatively in the docked
      conformation by using MOPAC 2002. These ligands were docked into a long, narrow
      channel of the enzyme leading to the molybdopterin active moiety, with hydrogen
      bonding and electrostatic interaction between the planar aromatic moiety of the
      ligand and the enzyme. Furthermore, SAR among inhibitors was investigated, which
      revealed that the oxo group of pyrazolopyrimidine analogs is essential for its
      activity and the tricyclic derivatives are shown to be more potent than bicyclic
      ones. The mode of interaction of the docked inhibitors was described in details.

PMID- 20039102
TI  - Gender differences in platelet aggregation in healthy individuals.
AB  - This study evaluated gender variability in platelet aggregation in response to
      common agonists. Platelet aggregation was measured in 36 healthy men and women
      free of any antiplatelet medication, aged 22-36 years, of Caucasian (White not of
      Hispanic origin), Hispanic, and African-American not of Hispanic origin. In this
      ex-vivo study, we investigated platelet aggregation in response to adenosine-5'
      diphosphate (ADP), epinephrine (EPI), arachidonic acid (AA) and collagen (COL),
      using a platelet ionized calcium aggregometer (Chrono-Log Co.). Platelet
      aggregation response to all tested agonists was higher in females than in males
      regardless of ethnicity. The most significant differences were observed with
      collagen (P < 0.01). Among the ethnic groups, Caucasian women were most prone to
      platelet aggregation. Gender is a determinant of agonist effects on platelet
      aggregability in healthy subjects.

PMID- 20039103
TI  - The significance of genetic polymorphisms of factor V Leiden and prothrombin in
      the preeclamptic Polish women.
AB  - Many studies established that gestational hypertension (GH) and preeclampsia (PE)
      are multifactorial diseases and disturbances in coagulation cascade have
      etiological significance. Inherited thrombophilias, like polymorphism of factor V
      (FV) Leiden and prothrombin (PTM) are considered to be involved in the PE
      development. The aim of this study was to determine the association between FV
      Leiden and G20210A of PTM gene polymorphism and GH/PE appearance. The study
      comprised 235 women: GH (n = 126, mean age 27.5 +/- 6.0 years), mild PE (n = 41,
      mean age 28.3 +/- 5.7 years), and severe PE (n = 68, mean age 28.5 +/- 5.7
      years). The control group consisted of 400 healthy pregnant women (mean age 27.5
      +/- 4.7 years). All women included in the study were white Caucasian of Polish
      origin, and were singleton pregnancies. The G1691A polymorphism of FV and G20210A
      polymorphism of PTM were detected using polymerase chain reaction/restriction
      fragment length polymorphism (PCR/RFLP) assays. For PTM G20210A polymorphism
      overrepresentation of heterozygous GA genotype (7.4 vs. 1.2%, P = 0.02) and of A
      allele (3.7 vs. 0.6%, P = 0.02) in the group of severe PE have been found. For FV
      G1691A polymorphism the overrepresentation of genotypes containing at least one
      mutated allele A (GA and AA) in the group of women with mild (9.7 vs. 3.5%, ns)
      and severe PE (8.8 vs. 3.5%, ns) was observed. Our results suggest the
      significant influence of G20210A prothrombin polymorphism and possible influence
      of G1691A factor V polymorphism in the development of severe preeclampsia.

PMID- 20039104
TI  - Propofol protects against hydrogen peroxide-induced oxidative stress and cell
      dysfunction in human umbilical vein endothelial cells.
AB  - Propofol has been reported to protect vascular endothelial cells against
      oxidative stress and dysfunction, but the underlying mechanisms are not clear. In
      this study, we studied hydrogen peroxide (H(2)O(2))-induced oxidative stress and
      cell dysfunction in human umbilical vein endothelial cells (HUVECs) and
      especially, their modulation by propofol. HUVECs were treated with different
      concentrations (0.1 and 0.5 mM) of H(2)O(2) for different times (1, 3, and 6 h).
      Then HUVECs were pretreated with different concentrations of propofol (10, 25,
      and 50 microM), followed by H(2)O(2) treatment (0.5 mM, 3 h). In another set of
      experiments, we pretreated cells with p38 mitogen-activated protein kinase (p38
      MAPK) inhibitor SB203580, followed by H(2)O(2) treatment (0.5 mM, 3 h). After
      treatment, oxidative stress, p38 MAPK phosphorylation, transcription factor NF
      kappaB activation, nitric oxide synthase (NOS) expression, nitric oxide (NO)
      production, and monocyte adhesion were measured. We observed H(2)O(2) treatment
      significantly induced oxidative stress, which could be attenuated by 25 microM
      propofol pretreatment. In addition, H(2)O(2) treatment significantly induced p38
      MAPK phosphorylation, NF-kappaB activation, NOS expression, and NO production.
      More importantly, our study showed these H(2)O(2)-induced changes were attenuated
      by propofol or SB203580 pretreatment. Further, we measured monocyte adhesion as a
      marker of endothelial cell dysfunction. H(2)O(2) increased the adhesion of
      monocytes to HUVECs, and propofol pretreatment reduced the adhesion in a fashion
      similar to SB203580. We concluded that propofol, by inhibiting p38 MAPK and NF
      kappaB activity, decreasing NOS expression, reducing NO production, could protect
      HUVECs which are exposed to oxidative stress and becoming dysfunctional.

PMID- 20039105
TI  - Population in vitro-in vivo correlation model for pramipexole slow-release oral
      formulations.
AB  - PURPOSE: To establish an in vitro-in vivo level A correlation (IVIVC) for
      pramipexole slow-release formulations. METHODS: The IVIVC was developed based on
      data from an immediate-release (IR) and three slow-release (SR) formulations of
      pramipexole; a fourth SR formulation was used for validation purposes. In vitro
      dissolution profiles were obtained from all SR formulations. Fifteen volunteers
      received all pramipexole formulations in a randomized cross-over trial. Data were
      analyzed using the population modelling approach as implemented in NONMEM VI.
      RESULTS: Dissolution profiles of the SR formulations were described by the
      Weibull model. The pharmacokinetics of the IR formulation were described by a two
      compartment disposition model with first-order absorption. Difference between the
      in vivo and in vitro estimates of the release rate constants (k(d)) from the
      Weibull function suggests the release process occurs faster in vivo.
      Pharmacokinetic profiles for SR formulations were described based on the in vitro
      release model with k(d) increased in 0.058 h(-1) and the population
      pharmacokinetic model developed from the IR formulation. CONCLUSION: A level A
      IVIVC was established and evaluated for the pramipexole SR formulations, which
      can be used in the future as a surrogate to avoid certain bioequivalence studies.

PMID- 20039106
TI  - Vocational interventions for unemployed: effects on work participation and mental
      distress. A systematic review.
AB  - INTRODUCTION: Unemployment is a growing problem worldwide. Unemployment or job
      loss is one of the most stressful of life events and can lead to diminished
      social status, disturbed social role patterns, financial debt, reduced self
      esteem and feelings of guilt. The purpose of this review was to determine the
      effectiveness of vocational interventions on work participation and mental
      distress for unemployed adults and to provide an overview of the characteristics
      of these interventions. METHODS: Medline, EMBASE and PsycINFO were systematically
      searched for studies published between 1990 and August 2008. Intervention studies
      aimed at work participation and helping with mental distress for the unemployed
      were included. Methodological quality of the included studies was assessed.
      RESULTS: Six articles based on five intervention studies, of which two randomized
      controlled trials, fulfilled all inclusion criteria. The methodological quality
      of the studies ranged from good to poor. All five interventions applied group
      training techniques aimed at promoting re-employment and/or improving mental
      health. The duration of the interventions varied from 1 week to 6 months. The
      interventions focused on acquiring job-search skills, maintaining paid work,
      personal development and preparedness against setbacks during the job-search
      process. Only one intervention study (randomized controlled trial) reported a
      significant effect on re-employment. CONCLUSIONS: Based on our review, we
      conclude that there is weak evidence to support the use of vocational
      interventions to improve work participation and limited evidence to reduce mental
      distress for the unemployed. We recommend further development and evaluation of
      return to work intervention strategies for unemployed individuals.

PMID- 20039107
TI  - Fluorescence lifetime tuning--a novel approach to study flip-flop kinetics in
      supported phospholipid bilayers.
AB  - In the present work we introduce a straightforward fluorescent assay that can be
      applied in studies of the transbilayer movement (flip-flop) of fluorescent lipid
      analogues across supported phospholipid bilayers (SPBs). The assay is based on
      the distance dependent fluorescence quenching by light absorbing surfaces.
      Applied to SPBs this effect leads to strong differences in fluorescence lifetimes
      when the dye moves from the outer lipid leaflet to the leaflet in contact with
      the support. Herein, we present the basic principles of this novel approach, and
      comment on its advantages over the commonly used methods for investigating flip
      flop dynamics across lipid bilayers. We test the assay on the fluorescent lipid
      analog Atto633-DOPE and the 3-hydroxyflavone F2N12S probe in SPBs composed of
      DOPC/ DOPS lipids. Moreover, we compare and discuss the flip-flop rates of the
      probes with respect to their lateral diffusion coefficients.

PMID- 20039108
TI  - Art therapy as a healing tool for sub-fertile women.
AB  - Although fertility is fundamental to spiritual health, it is often taken for
      granted. When a desired pregnancy fails to occur, stress and grief frequently
      follow. Visual expression of feelings through "art therapy" has proved a powerful
      healing tool for women brave enough to give it a try at the McMaster University
      Fertility Clinic. The objective and subjective findings of this ongoing project
      suggest that through simple visual self-expression, stress, anxiety and
      hopelessness may be reduced. This form of art therapy also provides a joyful
      social experience of sharing with other women, who are dealing with these issues.

PMID- 20039109
TI  - Mitochondrial matters in Parkinson disease: introduction.
AB  - Individuals with Parkinson disease (PD) are encountered frequently and have
      progressively severe neurologic changes. The central nervous system changes
      involve dopaminergic neurons in the basal ganglia and substantia nigra. Although
      usually sporadic, rare forms of PD are familial and the responsible genes have
      been identified. These genes affect mitochondrial function and can be studied in
      animals. Brains of affected animals reveal consequences of reactive oxygen
      species (ROS)--quinones, dopamine oxidation products, tyrosine nitration, lipid
      peroxidation and amino-aldehyde adducts. The three genes are important for
      maintaining physical and functional mitochondrial integrity. The cumulative
      effects of mitochondrial dysfunction, particularly those mediated by ROS,
      ultimately lead to at least some of the clinical and pathologic changes of PD.

PMID- 20039110
TI  - Predicting friendship quality in autism spectrum disorders and typical
      development.
AB  - The role played by social relationship variables (attachment security; mother
      child relationship qualities) and social-cognitive capacities (theory of mind)
      was examined in both observed friendship behaviors and in children's descriptions
      of friendships (age 8-12) with high functioning children with autism spectrum
      disorders (HFASD) (n = 44) and with typical development (TYP) (n = 38). Overall,
      half of the HFASD sample (54.45%) reported maternal attachment security,
      corroborating data from younger children with ASD. The hypothesized predictors
      and their interrelations had both direct and indirect effects on friendship for
      both groups of children, highlighting the importance of these factors in
      children's friendship development and suggesting both compensatory and
      amplification mechanisms for friendship qualities. Practical and clinical
      implications are discussed for friendship support in both ASD and TYP.

PMID- 20039111
TI  - Autism and ADHD symptoms in patients with OCD: are they associated with specific
      OC symptom dimensions or OC symptom severity?
AB  - In obsessive-compulsive disorder (OCD), the relationship between autism spectrum
      disorders (ASD), attention-deficit/hyperactivity disorder (ADHD) symptom, and
      obsessive-compulsive (OC) symptom dimensions and severity has scarcely been
      studied. Therefore, 109 adult outpatients with primary OCD were compared to 87
      healthy controls on OC, ADHD and ASD symptoms. OCD patients showed increased ADHD
      and autism symptom frequencies, OCD + ADHD patients reporting more autism
      symptoms (particularly attention switching and social skills problems) than OCD -
      ADHD patients. Attention switching problems were most significant predictors of
      OC symptom dimensions (except hoarding) and of symptom severity. Hoarding was not
      associated with elevated autism scale scores, but with inattention. In
      conclusion, attention switching problems may reflect both symptom overlap and a
      common etiological factor underlying ASD, ADHD and OCD.

PMID- 20039112
TI  - Viewing sexually-explicit materials alone or together: associations with
      relationship quality.
AB  - This study investigated associations between viewing sexually-explicit material
      (SEM) and relationship functioning in a random sample of 1291 unmarried
      individuals in romantic relationships. More men (76.8%) than women (31.6%)
      reported that they viewed SEM on their own, but nearly half of both men and women
      reported sometimes viewing SEM with their partner (44.8%). Measures of
      communication, relationship adjustment, commitment, sexual satisfaction, and
      infidelity were examined. Individuals who never viewed SEM reported higher
      relationship quality on all indices than those who viewed SEM alone. Those who
      viewed SEM only with their partners reported more dedication and higher sexual
      satisfaction than those who viewed SEM alone. The only difference between those
      who never viewed SEM and those who viewed it only with their partners was that
      those who never viewed it had lower rates of infidelity. Implications for future
      research in this area as well as for sex therapy and couple therapy are
      discussed.

PMID- 20039113
TI  - A further assessment of Blanchard's typology of homosexual versus non-homosexual
      or autogynephilic gender dysphoria.
AB  - In a series of important but now highly controversial articles, Blanchard
      examined associations of sexual orientation and transvestic fetishism among male
      to-female (MTF) transgender persons in Toronto, Canada. Transvestic fetishism was
      rare among the homosexuals but prevalent among the non-homosexuals. Subtypes of
      non-homosexual MTFs (heterosexual, bisexual, and asexual) were consistently high
      with regard to transvestic fetishism. Non-linear associations of a continuous
      measurement of sexual attraction to women (gynephilia) and transvestic fetishism
      were interpreted in terms of an etiological hypothesis in which transvestic
      fetishism interferes with the early development of heterosexuality. Blanchard
      concluded that homosexual versus non-homosexual sexual orientation is a dominant
      and etiologically significant axis for evaluating and understanding this
      population. We further assessed these findings among 571 MTFs from the New York
      City metropolitan area. Using the Life Chart Interview, multiple measurements of
      transvestic fetishism were obtained and classified as lifetime, lifecourse
      persistent, adolescent limited, and adult onset. Large (but not deterministic)
      differences in lifetime, lifecourse persistent, and adolescent limited
      transvestic fetishism were found between the homosexuals and non-homosexuals.
      Contrary to Blanchard, differences in transvestic fetishism were observed across
      subtypes of the non-homosexuals, and linear (not curvilinear) associations were
      found along a continuous measurement of gynephilia and transvestic fetishism. Age
      and ethnicity, in addition to sexual orientation, were found to be statistically
      significant predictors of transvestic fetishism. The clinical, etiological, and
      sociopolitical implications of these findings are discussed.

PMID- 20039114
TI  - Male sexual orientation in independent samoa: evidence for fraternal birth order
      and maternal fecundity effects.
AB  - In Western cultures, male androphiles tend to have greater numbers of older
      brothers than male gynephiles (i.e., the fraternal birth order effect). In the
      non-Western nation of Independent Samoa, androphilic males (known locally as
      fa'afafine) have been shown to have greater numbers of older brothers, older
      sisters, and younger brothers (Vasey & VanderLaan, 2007). It is unclear, however,
      whether the observed older brother effect, in the context of the additional
      sibling category effects, represented a genuine fraternal birth order effect or
      was simply associated with elevated maternal fecundity. To differentiate between
      these two possibilities, this study employed a larger, independent replication
      sample of fa'afafine and gynephilic males from Independent Samoa. Fa'afafine had
      greater numbers of older brothers and sisters. The replication sample and the
      sample from Vasey and VanderLaan were then combined, facilitating a comparison
      that showed the older brother effect was significantly greater in magnitude than
      the older sister effect. These results suggest that fraternal birth order and
      maternal fecundity effects both exist in Samoa. The existence of these effects
      cross-culturally is discussed in the context of biological theories for the
      development of male androphilia.

PMID- 20039115
TI  - The "participating victim" in the study of erotic experiences between children
      and adults: an historical analysis.
AB  - During the 20th century, erotic experiences between minors and adults occupied a
      position of increasing interest, both public as well as scientific. In this area
      of research, one of the most notable evolutions in how these experiences are
      treated has been the progressive disappearance and/or the intense redefinition of
      what earlier researchers called "participating victims," i.e., minors apparently
      interested in accepting and/or sustaining these relationships. The present work,
      through a comparative analysis of the literature, seeks to substantiate this
      transformation during the second third of the 20th century. It will also argue
      that this evolution can be fundamentally explained in terms of the intense
      emotional, moral, and ideological importance that is ascribed to these
      experiences in the rise of the current victimological paradigm. Finally, this
      study endeavors to contribute to the understanding of childhood and the
      scientific study of child sexuality as well as of these experiences with adults.

PMID- 20039116
TI  - Automatic removal of eye-movement and blink artifacts from EEG signals.
AB  - Frequent occurrence of electrooculography (EOG) artifacts leads to serious
      problems in interpreting and analyzing the electroencephalogram (EEG). In this
      paper, a robust method is presented to automatically eliminate eye-movement and
      eye-blink artifacts from EEG signals. Independent Component Analysis (ICA) is
      used to decompose EEG signals into independent components. Moreover, the features
      of topographies and power spectral densities of those components are extracted to
      identify eye-movement artifact components, and a support vector machine (SVM)
      classifier is adopted because it has higher performance than several other
      classifiers. The classification results show that feature-extraction methods are
      unsuitable for identifying eye-blink artifact components, and then a novel peak
      detection algorithm of independent component (PDAIC) is proposed to identify eye
      blink artifact components. Finally, the artifact removal method proposed here is
      evaluated by the comparisons of EEG data before and after artifact removal. The
      results indicate that the method proposed could remove EOG artifacts effectively
      from EEG signals with little distortion of the underlying brain signals.

PMID- 20039117
TI  - A public health approach to children's mental health services: possible solutions
      to current service inadequacies.

PMID- 20039118
TI  - Genetic diversity and phylogenetic relationships of two closely related northeast
      China Vicia species revealed with RAPD and ISSR markers.
AB  - RAPD and ISSR analyses revealed genetic diversity and relationships among 11
      populations of two closely related northeast China Vicia species, Vicia
      ramuliflora and V. unijuga. Both methods yielded similar and complementary
      results, showing high genetic diversity. Vicia ramuliflora had 100% polymorphic
      loci in both RAPD and ISSR, and V. unijuga had 100% polymorphic loci for RAPD and
      98.96% for ISSR. Genetic differentiation was moderate among populations of each
      species. Genetic variation was distributed mainly within populations for the two
      species. The high level of gene flow was important for the allocation of genetic
      variation. The UPGMA dendrogram and principal coordinates analysis at the level
      of individuals and populations showed that V. ramuliflora and V. unijuga were
      more closely related than either of them was to the outgroup species, V. cracca.
      The small molecular variance of V. ramuliflora and V. unijuga supports the
      conclusion that these two species had a common ancestor.

PMID- 20039119
TI  - The Ty1-copia families SALIRE and Cotzilla populating the Beta vulgaris genome
      show remarkable differences in abundance, chromosomal distribution, and age.
AB  - Long terminal repeat (LTR) retrotransposons are major components of plant genomes
      influencing genome size and evolution. Using two separate approaches, we
      identified the Ty1-copia retrotransposon families Cotzilla and SALIRE in the Beta
      vulgaris (sugar beet) genome. While SALIRE elements are similar to typical Ty1
      copia retrotransposons, Cotzilla elements belong to a lineage called Sireviruses.
      Hallmarks of Cotzilla retrotransposons are the existence of an additional
      putative env-like open reading frame upstream of the 3'LTR, an extended gag
      region, and a frameshift separating the gag and pol genes. Detected in a c ( 0 )
      t-1 DNA library, Cotzilla elements belong to the most abundant retrotransposon
      families in B. vulgaris and are relatively homogenous and evolutionarily young.
      In contrast, the SALIRE family has relatively few copies, is diverged, and most
      likely ancient. As revealed by fluorescent in situ hybridization, SALIRE elements
      target predominantly gene-rich euchromatic regions, while Cotzilla
      retrotransposons are abundant in the intercalary and pericentromeric
      heterochromatin. The analysis of two retrotransposons from the same subclass
      contrasting in abundance, age, sequence diversity, and localization gives insight
      in the heterogeneity of LTR retrotransposons populating a plant genome.

PMID- 20039120
TI  - Defining replication origin efficiency using DNA fiber assays.
AB  - The timely duplication of eukaryotic genomes depends on the coordinated
      activation of thousands of replication origins distributed along the chromosomes.
      Origin activation follows a temporal program that is imposed by the chromosomal
      context and is under the control of S-phase checkpoints. Although the general
      mechanisms regulating DNA replication are now well-understood at the level of
      individual origins, little is known on the coordination of thousands of
      initiation events at a genome-wide level. Recent studies using DNA combing and
      other single-molecule assays have shown that eukaryotic genomes contain a large
      excess of replication origins. Most of these origins remain "dormant" in normal
      growth conditions but are activated when fork progression is impeded. In this
      review, we discuss how DNA fiber technologies have changed our view of eukaryotic
      replication programs and how origin redundancy contributes to the maintenance of
      genome integrity in eukaryotic cells.

PMID- 20039122
TI  - Students learn systems-based care and facilitate system change as stakeholders in
      a free clinic experience.
AB  - Systems-based practice (SBP) is rarely taught or evaluated during medical school,
      yet is one of the required competencies once students enter residency. We believe
      Texas A&M College of Medicine students learn about systems issues informally, as
      they care for patients at a free clinic in Temple, TX. The mandatory free clinic
      rotation is part of the Internal Medicine clerkship and does not include formal
      instruction in SBP. During 2008-2009, a sample of students (n = 31) on the IMED
      clerkship's free clinic rotation participated in a program evaluation/study
      regarding their experiences. Focus groups (M = 5 students/group) were held at the
      end of each outpatient rotation. Students were asked: "Are you aware of any
      system issues which can affect either the delivery of or access to care at the
      free clinic?" Data saturation was reached after six focus groups, when
      investigators noted a repetition of responses. Based upon investigator consensus
      opinion, data collection was discontinued. Based upon a content analysis, six
      themes were identified: access to specialists, including OB-GYN, was limited;
      cost containment; lack of resources affects delivery of care; delays in care due
      to lack of insurance; understanding of larger healthcare system and free clinic
      role; and delays in tests due to language barriers. Medical students were able to
      learn about SBP issues during free clinic rotations. Students experienced how SBP
      issues affected the health care of uninsured individuals. We believe these
      findings may be transferable to medical schools with mandatory free clinic
      rotations.

PMID- 20039121
TI  - High levels of uPA and PAI-1 predict a good response to anthracyclines.
AB  - Urokinase-type plasminogen activator (uPA) and its main inhibitor (PAI-1) were
      shown with level 1 evidence to be prognostic factors for primary breast cancer.
      Our preliminary retrospective study on a cohort of 1,220 consecutive patients
      hinted that uPA and PAI-1 could also serve as predictive factors for systemic
      therapy, namely that patients with high levels of the two markers benefit much
      more from anthracycline-based chemotherapy than patients with low levels of the
      two markers. The latter could equally well be treated with less toxic CMF-based
      chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). The
      retrospective study, however, suffered from severely uneven patient and tumor
      characteristics as the patients were treated per institutional guidelines valid
      at the time and were not randomized between the anthracycline and CMF arms. In
      the present paper, we attempted to remedy this shortcoming and recheck our
      previous observations on more balanced data. To this end we employed a custom
      made computer algorithm that selected 180 patients out of a total of 1,220
      patients such that we obtained very well balanced anthracycline and CMF arms
      according to patient and tumor characteristics. Moreover, the low and high
      uPA/PAI-1 subgroups within both arms were also completely balanced. The algorithm
      in a way created a similar setting to that of a randomized study at the expense
      of greatly reducing the number of patients included into the study. In this
      setting, we observed the 3-year disease-free survival (DFS) in all four subgroups
      (according to treatment and levels of markers: both uPA and PAI-1 low versus one
      or both high). We report that the 3-year DFS in the CMF arm differed
      significantly: 87.1% for patients with low levels of markers versus 77.0% for
      patients with high levels of markers (P = 0.044, HR = 2.81, 95% CI = 0.98-8.04).
      On the other hand, the 3-year DFS in the anthracycline arm did not differ much
      between the two marker level subgroups: 85.2% for patients with low levels of
      markers versus 81.8% for patients with high levels of markers. Our observation
      points out that worse prognosis correlated to high uPA and PAI-1 levels can be
      reversed by treatment efficacy achieved through anthracycline-based chemotherapy.
      Based on this observation, we hypothesize that uPA/PAI-1 combination could be
      predictive for response to systemic therapy.

PMID- 20039123
TI  - Learning ethics through everyday problems: informed consent.
AB  - The teaching of bioethics and its importance in clinical relationships is to a
      certain extent complicated when we address students of medicine, young people who
      are more used to dealing with and solving strictly clinical problems. Informed
      Consent is one of the aspects of professional practice that is generally and
      widely accepted in Western societies, although difficulties are still encountered
      in explaining it from a purely theoretical model. This situation led us to design
      an educational strategy to make the Informed Consent concept more understandable.

PMID- 20039124
TI  - The association of glomerular filtration rate and erectile dysfunction with
      severity of coronary artery disease in patients presenting with chest pain.
AB  - BACKGROUND: The most common cause of death in patients with chronic kidney
      disease is cardiovascular. Coexistence of reduced estimated glomerular filtration
      rate (eGFR) and erectile dysfunction (ED) may predate severe underlying coronary
      artery disease (CAD). The aim of this study was to evaluate the predictive value
      of presence and severity of ED and reduced estimated eGFR in the risk
      stratification of CAD in patients with chest pain. METHODS: Two hundred and sixty
      five consecutive male patients with chest pain were included. All patients
      underwent exercise stress test (EST), of whom those with positive EST underwent
      coronary angiography. eGFR was calculated and sexual health inventory for men
      (SHIM) form was applied to evaluate ED. The relation between SHIM scores, eGFR
      and the number of arteries with significant lesions was evaluated. RESULTS: Of
      the 265 male patients, 105 had positive EST while the remaining 160 patients had
      negative EST. ED was present in 62 patients (38.8%) in the EST (-) group and in
      64 patients (61%) in the EST (+) group (P = 0.000). In the EST (+) group,
      coronary angiography (CAG) revealed normal coronary anatomy or insignificant
      coronary lesions in 19 (18%), one-vessel disease in 45 (43%), two-vessel disease
      in 22 (21%) and three-vessel disease in 19 (18%) patients, respectively. The
      lowest ED prevalence (36.8%) was seen in patients who had normal coronary anatomy
      or insignificant coronary lesions while the highest prevalence was in those with
      three-vessel disease (89.5%). When eGFR were taken into account, there was a
      significant difference between the groups as well (107.2 +/- 19.2 ml/min in the
      EST (-) group versus 94.1 +/- 20.0 ml/min in the EST (+) group; P = 0.001).
      CONCLUSION: The presence and severity of ED and reduced eGFR are associated with
      the severity of underlying CAD in patients presenting with chest pain, and they
      could be implemented in the risk stratification of these patients.

PMID- 20039125
TI  - Association between N-terminal pro-brain natriuretic peptide and acute ischemic
      stroke in patients on chronic hemodialysis.
AB  - BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) has been
      reported as a predictor for ischemic stroke in general population. However,
      predictive value of plasma NT-proBNP for acute ischemic stroke in patients on
      chronic hemodialysis has not been well established. The aim of this study was to
      determine whether NT-proBNP could predict acute ischemic stroke in patients on
      chronic hemodialysis. METHODS: This study was designed prospectively. Clinical,
      laboratory, and echocardiographic variables were assessed in 72 patients on
      chronic hemodialysis. The plasma levels of NT-proBNP were measured by
      immunoassay. RESULTS: During the follow-up period of 45 months, 11 patients had
      an acute ischemic stroke. The Kaplan-Meier plot showed an increased frequency of
      acute ischemic stroke in patients with plasma levels of NT-proBNP above the
      median values compared to patients with lower concentrations (P = 0.028). The
      multivariate Cox proportional hazard models showed that the NT-proBNP was a
      significant independent predictor of acute ischemic stroke after adjustment for
      age, sex, mean blood pressure, diabetes, serum cholesterol levels, left
      ventricular mass index, and left ventricular fractional shortening (HR 6.66, 95%
      CI, 1.22-36.48, P = 0.029). CONCLUSIONS: Our data suggest that plasma NT-proBNP
      levels predict the risk of acute ischemic stroke in patients on chronic
      hemodialysis.

PMID- 20039126
TI  - Vitamin D and cardiovascular risk.
AB  - Vitamin D deficiency results in abnormal mineralization of bones and has resulted
      in prevention programs for children with supplementation when they are breast
      fed. Further activities of vitamin D relate to defence of microbial infections,
      e.g. tuberculosis, prevention of cancer, contractility of muscle cells and
      counteraction of congestive heart failure. Given early reports in the 1960s on
      deleterious effects of vitamin D supplementation in rodents, that is ectopic
      media ossification of arterial vessels, a pro-atherogenic function had been
      anticipated for humans as well. However, cross-sectional studies reveal that
      vitamin D deficiency in humans is associated with elevated blood pressure and
      propagation of atherogenesis. These contradictory findings on the progression of
      atherosclerosis may be reconciled by dissecting the activation mechanism(s) of
      vitamin D in rodents versus humans. Notably, novel findings convincingly indicate
      that vitamin D exerts anti-inflammatory effects. In conclusion, vitamin D
      supplementation in adults may be regarded as simple means with few potential side
      effects to prevent atherogenesis or halt its progression and combat arterial
      hypertension. Adjustment of vitamin D dosing regimens is required in patients
      with chronic kidney disease; however, prospective clinical trials are urgently
      needed to guide these recommendations with evidence.

PMID- 20039128
TI  - Rapid discrimination and classification of the Lactobacillus plantarum group
      based on a partial dnaK sequence and DNA fingerprinting techniques.
AB  - The Lactobacillus plantarum group comprises five very closely related species.
      Some species of this group are considered to be probiotic and widely applied in
      the food industry. In this study, we compared the use of two different molecular
      markers, the 16S rRNA and dnaK gene, for discriminating phylogenetic
      relationships amongst L. plantarum strains using sequencing and DNA
      fingerprinting. The average sequence similarity for the dnaK gene (89.2%) among
      five type strains was significantly less than that for the 16S rRNA (99.4%). This
      result demonstrates that the dnaK gene sequence provided higher resolution than
      the 16S rRNA and suggests that the dnaK could be used as an additional
      phylogenetic marker for L. plantarum. Species-specific profiles of the
      Lactobacillus strains were obtained with RAPD and RFLP methods. Our data indicate
      that phylogenetic relationships between these strains are easily resolved using
      sequencing of the dnaK gene or DNA fingerprinting assays.

PMID- 20039127
TI  - Bone mineral density in patients on maintenance dialysis.
AB  - Disorders of bone and mineral metabolism affect almost all patients with advanced
      chronic kidney disease (CKD). High prevalence of decreased bone mineral density
      has been reported in this population; however, the role and diagnostic utility of
      bone density measurements are not well established. The incidence of bone
      fractures is high in patients with ESRD, but the association between fractures
      and bone density is not obvious. A recent meta-analysis suggested that decreased
      density at the radius might be associated with higher overall fracture risk.
      Changes in bone mineral density reflect several underlying pathological
      processes, such as vitamin D deficiency, estrogen deficiency and changes in bone
      turnover. The response of bone to these factors and processes is not uniform: it
      can vary in different compartments of the same bone or in different bones of the
      skeleton. Therefore, it is important to differentiate between the various types
      of bone. This may be possible by proper selection of the measurement site or
      using methods such as quantitative bone computed tomography. Previous studies
      used different methods and measured bone mineral density at diverse sites of the
      skeleton, which makes the comparison of their results very difficult. The
      association between changes in bone mineral metabolism and cardiovascular
      mortality is well known in ESRD patients. Studies also suggest that low bone
      density itself might be an indicator for high risk of cardiovascular events and
      poor overall outcome in this population. Some of the risk factors of low bone
      mineral density, such as vitamin D or estrogen deficiency, are potentially
      modifiable. Further studies are needed to elucidate if interventions modifying
      these risk factors will have an impact on clinical outcomes. In this review, we
      discuss the options for and problems of assessment of bone density and summarize
      the literature about factors associated with low bone density and its link to
      clinical outcomes in patients on maintenance dialysis.

PMID- 20039129
TI  - Oral health of adults with serious mental illnesses: a review.
AB  - (A) To assess the prevalence of suboptimal oral health in adults with SMI in
      studies published in 1971-2009; (B) To describe approaches that promote oral
      health among adults with SMI. A total of 57 randomized, quasi-randomized, cross
      section, and cohort studies from samples of 38-4,769 mental health consumers are
      identified through database, journal, and Internet searches (Cochrane, FASTSTATS,
      PUBMED, WHO.int). Selected studies are inclusive for the sample, reported
      statistical power, and external validity. Oral health adverse outcomes
      (xerostomia, sialorrhoea, dental caries, extracted teeth, malocclusion,
      periodontal disease, edentulous, oral cancer) are considered as measurable
      outcomes. This review suggests a substantial prevalence of suboptimal oral health
      (61%) among individuals with serious mental illnesses. The following outcomes are
      mostly met: xerostomia, gross caries, decayed teeth, and periodontal disease.
      Poor oral hygiene, higher intake of carbonates, poor perception of oral health
      self-needs, length of psychotropic treatment, and less access to dental care
      determine suboptimal oral health among this population. Further replication of
      this research should generate gender-wise ethnic cohorts, including detailed
      observations of environmental factors, and medical problems that contribute to
      suboptimal oral health. This review highlights the importance of bridging dental
      health education to psychiatric rehabilitation programs.

PMID- 20039130
TI  - A measure of dysfunctional eating-related cognitions in people with psychotic
      disorders.
AB  - Obesity and binge eating disorder are common in individuals with psychotic
      disorders. Eating and weight-related cognitions are known to influence eating
      behaviors. The study was designed to assess the psychometric properties of the
      Mizes Anorectic Cognitions Questionnaire (MAC-R) in patients with psychotic
      disorders. Binge eating disorder (BED), body mass index (BMI), the MAC-R and the
      three factor eating questionnaire (TFEQ) were assessed in 125 patients with a
      diagnosis of schizophrenia or schizoaffective disorder. Whereas the MAC-R has not
      acceptable psychometric properties, a brief version of the MAC-R (BMAC) has good
      psychometrical properties and is correlated with TFEQ and BMI. Binge eating
      disorder is also correlated to the Rigid Weight Regulation and Fear of Weight
      Gain subscale. The BMAC is a useful brief measure to assess eating and weight
      related cognitions in people with psychotic disorders.

PMID- 20039131
TI  - Fast cyclic electron transport around photosystem I in leaves under far-red
      light: a proton-uncoupled pathway?
AB  - Fast cyclic electron transport (CET) around photosystem I (PS I) was observed in
      sunflower (Helianthus annuus L.) leaves under intense far-red light (FRL) of up
      to 200 mumol quanta m(-2) s(-1). The electron transport rate (ETR) through PS I
      was found from the FRL-dark transmittance change at 810 and 950 nm, which was
      deconvoluted into redox states and pool sizes of P700, plastocyanin (PC) and
      cytochrome f (Cyt f). PC and P700 were in redox equilibrium with K(e) = 35
      (DeltaE(m) = 90 mV). PS II ETR was based on O(2) evolution. CET [(PS I ETR) - (PS
      II ETR)] increased to 50-70 mumol e(-) m(-2) s(-1) when linear electron transport
      (LET) under FRL was limited to 5 mumol e(-) m(-2) s(-1) in a gas phase containing
      20-40 mumol CO(2) mol(-1) and 20 mumol O(2) mol(-1). Under these conditions,
      pulse-saturated fluorescence yield F(m) was non-photochemically quenched;
      however, F(m) was similarly quenched when LET was driven by low green or white
      light, which energetically precluded the possibility for active CET. We suggest
      that under FRL, CET is rather not coupled to transmembrane proton translocation
      than the CET-coupled protons are short-circuited via proton channels regulated to
      open at high DeltapH. A kinetic analysis of CET electron donors and acceptors
      suggests the CET pathway is that of the reversed Q-cycle: Fd -> (FNR) -> Cyt c(n)
      -> Cyt b(h) -> Cyt b(l) -> Rieske FeS -> Cyt f -> PC -> P700 ->-> Fd. CET is
      activated when PQH(2) oxidation is opposed by high DeltapH, and ferredoxin (Fd)
      is reduced due to low availability of e(-) acceptors. The physiological
      significance of CET may be photoprotective, as CET may be regarded as a mechanism
      of energy dissipation under stress conditions.

PMID- 20039132
TI  - Enzymatic properties of the ferredoxin-dependent nitrite reductase from
      Chlamydomonas reinhardtii. Evidence for hydroxylamine as a late intermediate in
      ammonia production.
AB  - The ferredoxin-dependent nitrite reductase from the green alga Chlamydomonas
      reinhardtii has been cloned, expressed in Escherichia coli as a His-tagged
      recombinant protein, and purified to homogeneity. The spectra, kinetic properties
      and substrate-binding parameters of the C. reinhardtii enzyme are quite similar
      to those of the ferredoxin-dependent spinach chloroplast nitrite reductase.
      Computer modeling, based on the published structure of spinach nitrite reductase,
      predicts that the structure of C. reinhardtii nitrite reductase will be similar
      to that of the spinach enzyme. Chemical modification studies and the ionic
      strength dependence of the enzyme's ability to interact with ferredoxin are
      consistent with the involvement of arginine and lysine residues on C. reinhardtii
      nitrite reductase in electrostatically-stabilized binding to ferredoxin. The C.
      reinhardtii enzyme has been used to demonstrate that hydroxylamine can serve as
      an electron-accepting substrate for the enzyme and that the product of
      hydroxylamine reduction is ammonia, providing the first experimental evidence for
      the hypothesis that hydroxylamine, bound to the enzyme, can serve as a late
      intermediate during the reduction of nitrite to ammonia catalyzed by the enzyme.

PMID- 20039133
TI  - Effects of scleral stiffness properties on optic nerve head biomechanics.
AB  - The biomechanical environment within the optic nerve head, important in glaucoma,
      depends strongly on scleral biomechanical properties. Here we use a range of
      measured nonlinear scleral stress-strain relationships in a finite element (FE)
      model of the eye to compute the biomechanical environment in the optic nerve head
      at three levels of intraocular pressure (IOP). Three stress-strain relationships
      consistent with the 5th, 50th and 95th percentiles of measured human scleral
      stiffness were selected from a pool of 30 scleral samples taken from 10 eyes and
      implemented in a generic FE model of the eye using a hyperelastic five-parameter
      Mooney-Rivlin material model. Computed strains within optic nerve head tissues
      depended strongly on scleral properties, with most of this difference occurring
      between the compliant and median scenarios. Also, the magnitudes of strains were
      found to be substantial even at normal IOP (up to 5.25% in the lamina cribrosa at
      15 mmHg), being larger than previously reported values even at normal levels of
      IOP. We conclude that scleras that are "weak", but still within the physiologic
      range, will result in appreciably increased optic nerve head strains and could
      represent a risk factor for glaucomatous optic neuropathy. Estimations of the
      deformation at the optic nerve head region, particularly at elevated IOP, should
      take into account the nonlinear nature of scleral stiffness.

PMID- 20039134
TI  - Optimization of MR phase-contrast-based flow velocimetry and shear stress
      measurements.
AB  - This study was designed to measure the pixel-by-pixel flow velocity and shear
      stress from phase-contrast MR images. An optimized method was suggested and the
      use of the method was confirmed. A self-developed, straight steady flow model
      system was scanned by MRI with a velocity-encoded phase-contrast sequence. In
      house developed software was used for the pixel-by-pixel flow velocity and shear
      stress measurements and the measurements were compared with physically measured
      mean velocity and shear stress. A comparison between the use of the in-house
      velocimetry software and a commercial velocimetry system was also performed.
      Curved steady flow models were scanned by phase-contrast MRI. Subsequently,
      velocity and shear stress were measured to confirm the shifted peak flow velocity
      and shear stress toward the outer side of the lumen. Peak velocity and shear
      stress were calculated for both the inner and outer half of the lumen and were
      statistically compared. The mean velocity measured with the use of in-house
      software had a significant correlation with the physical measurements of mean
      velocity; in addition, the measurement was more precise compared to the
      commercial system (R(2) = 0.85 vs. 0.75, respectively). The calculated mean shear
      stress had a significant correlation with the physical measurements of mean shear
      stress (R(2) = 0.95). The curved flow model showed a significantly shifted peak
      velocity and shear stress zones toward the outside of the flow (P < 0.0001). The
      technique to measure pixel-by-pixel velocity and shear stress of steady flow from
      velocity-encoded phase-contrast MRI was optimized. This technique had a good
      correlation with physical measurements and was superior to a commercially
      available system.

PMID- 20039135
TI  - Don't stop at two.
AB  - An asymptomatic 35-year-old woman with history of coarctation repair underwent
      routine echo. This showed a bicuspid aortic valve with a significant gradient in
      the left ventricular outflow tract (LVOT). The anterior mitral valve leaflet
      appeared redundant. Transoesophageal echo showed thickened chordae tendineae from
      both mitral valve leaflets inserted into a single postero-medial papillary muscle
      a parachute mitral valve. During systole, there was anterior motion of redundant
      mitral chordae into the LVOT producing significant obstruction. A diagnosis of
      partial Shone complex was made. She was referred for mitral (and possibly aortic)
      valve surgery. The combination of aortic coarctation with bicuspid aortic valve
      should stimulate a search for other levels of systemic obstruction-don't stop at
      two!

PMID- 20039136
TI  - Use of cardiac magnetic resonance imaging in the diagnosis of Takotsubo
      cardiomyopathy: another imaging feature added.

PMID- 20039137
TI  - Cardiac resynchronization therapy; evaluation by advanced imaging techniques.

PMID- 20039138
TI  - Medium selection and effect of higher oxygen concentration pulses on Metarhizium
      anisopliae var. lepidiotum conidial production and quality.
AB  - Rice and oat flours were analyzed as media for the production of conidia by M.
      anisopliae var. lepidiotum. The presence of peptone increased conidia yield
      regardless of the substrate used; however, the highest yield was achieved on oat
      flour media. The effect of oxygen on conidia production using oat-peptone medium
      was also studied at two levels: Normal atmosphere (21% O(2)) and Oxygen-rich
      pulses (26% O(2)). Maximum conidia production (4.25 x 10(7) conidia cm(-2)) was
      achieved using 26% O(2) pulses after 156 h of culture, which was higher than 100%
      relative to conidial levels under normal atmosphere. Conidia yield per gram of
      biomass was 2.6 times higher with 26% O(2) (1.12 x 10(7) conidia mg(-1)). Conidia
      quality parameters, such as germination and hydrophobicity, did not show
      significant differences (P < 0.05) between those treatments. Bioassays
      parameters, using Tenebrio molitor adults, were analyzed for conidia obtained in
      both atmospheres and data were fitted to an exponential model. The specific
      mortality rates were 2.22 and 1.26 days(-1), whereas lethal times for 50%
      mortality were 3.90 and 4.31 days, for 26% O(2) pulses and 21% O(2) atmosphere,
      respectively. These results are relevant for production processes since an oxygen
      increase allowed superior levels of conidia by M. anisopliae without altering
      quality parameters and virulence toward Tenebrio molitor adults.

PMID- 20039140
TI  - The challenge of understanding mortality changes among street youth.
AB  - According to a cohort study conducted in Montreal, Quebec from 1995 to 2000, the
      mortality rate among street youth was 921/100,000 person-years. Several new
      community initiatives aiming to increase access to housing and to social and
      health services for the homeless were implemented in the city between 2000 and
      2003. This study aims to update the mortality rate estimate for the period 2001
      2006 and to examine factors that could explain a difference between rates, if
      any. A second cohort study was conducted between 2001 and 2006. The Cohort 2
      mortality rate was computed and compared with the Cohort 1 rate. Several analyses
      were then carried out: (1) mortality rates in the general population were
      compared with street youth rates using standardized mortality ratios (SMR); (2)
      Cohorts 1 and 2 distributions of risk factors for mortality were examined, and
      their effects were assessed using multivariate proportional hazards regression
      analyses carried out on a combined Cohorts 1 and 2 dataset. Mortality rate among
      street youth decreased by 79% while it declined by only 19% in the general
      population; the SMR for Cohort 1 was higher than for Cohort 2 (11.6 versus 3.0).
      Multivariate proportional hazards regression analyses yielded estimates that were
      close to the model's estimates based on Cohort 1 data only, and participation in
      Cohort 1 was an independent predictor of mortality, with an adjusted hazard ratio
      of 9.0. The mortality decline cannot be completely explained by a similar
      decrease among the general population or by a difference in distribution of risk
      factors for mortality between the two cohorts. Field workers suggested that the
      decrease in heroin consumption they had observed in the streets might have
      contributed to the mortality decline. We then performed additional analyses which
      showed that even though the proportion of street youth currently using heroin
      decreased significantly between 1995 and 2005, the association between heroin use
      and mortality was not significant (adjusted hazard ratio of 0.9; 95% CI, 0.4 to
      2.3). It seems that various factors could have contributed to the decline in
      mortality rates among street youth, one plausible factor being the implementation
      of new services for the homeless. This study underscores the importance of
      monitoring risky behaviors among vulnerable populations to ensure that morbidity
      and mortality data among these populations is correctly interpreted. Setting up a
      system to monitor the drug market could improve the quality of information
      collected.

PMID- 20039139
TI  - Multicellular genesis of leaf primordium was demonstrated via chimaeric
      transgenic plant of maize (Zea mays L.) regenerated from Type II calli.
AB  - Type-II embryonic calli were induced from immature embryos of maize (Zea mays L.)
      genotype YD and bombarded with beta-glucuronidase gene. Bombarded calli were
      proliferated on normal N6 medium for 2 weeks at 26 degrees C in the dark and
      selected on N6 medium containing 1 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D)
      and 5 mg/l phosphinothricin (PPT) but without casamino acids and proline under
      the same conditions for 14 days. Regeneration was carried out on hormone-free MS
      medium containing 5 mg/l phosphinothricin at 26 degrees C under 3000 lux
      illumination. Plants over 8 cm were transplanted into soil and sprayed with 250
      mg/l phosphinothricin when two new leaves appeared. Except normal transgenic
      plants, chimaeric transgenics also were regenerated in the present work. The
      expression pattern of beta-glucuronidase gene in leaves of chimaeric transgenic
      plant revealed that more than one cell formed leaf primordium at the initial
      stage, and filial cells stemed from each cell in leaf primordium arranged in a
      row longitudinally from leaf base to leaf apex. There was a clear boundary as a
      straight line between the area formed by transformed cells and the area formed by
      normal cells. A hypothesis was put forward that the primitive cells in leaf
      primordium divided in a longitudinal style, resulted in leaf elongation, then the
      filial cells divided transversally and synchronously toward the outside to
      broaden the leaf.

PMID- 20039141
TI  - Telemetry system for slow wave measurement from the small bowel.
AB  - A telemetry capsule system was designed and implemented to measure the slow wave
      activity of the small bowel, which is an important parameter for the diagnosis of
      gastric diseases. The capsule amplified the slow wave signal from the
      intraluminal electrodes, and transmitted the digitally sampled data by means of a
      radio frequency transmitter. The implemented capsule (11 x 21 mm(2)) was smaller
      than a commercially available capsule endoscope, and it can remain active for
      more than 18 h. The feasibility of using this capsule was investigated by
      conducting in vitro experiments, and the average motility signals of the ileum,
      jejunum, and colon were measured as 6.1, 10.2, and 1.5 cycles per minute,
      respectively.

PMID- 20039142
TI  - Cell-level temperature distributions in skeletal muscle post spinal cord injury
      as related to deep tissue injury.
AB  - Deep tissue injury (DTI) is a severe pressure ulcer, which initiates in skeletal
      muscle tissue under intact skin. Patients with spinal cord injury (SCI) are
      especially vulnerable to DTI, due to their impaired motosensory capacities. The
      underlying mechanisms that lead to DTI are, however, still poorly understood.
      This study focuses on cell-level temperature distributions in muscles of patients
      with SCI, which typically contain thinner muscle fibers and fewer capillaries. It
      has been shown previously by our group that ischemic muscles of rat models of DTI
      cool down mildly and locally, which is very likely to slow the diffusivity of
      metabolites in the ischemic regions. However, it is unclear how these temperature
      decreases affect diffusivity at the scale of individual muscle cells in the
      microanatomy of SCI patients. We hypothesize that a 2 degrees C drop in the
      temperature of inflowing capillary blood, as shown in our animal studies, has a
      substantial effect on lowering the diffusivity of metabolites in skeletal muscle,
      but the pathological microanatomy in the chronic phase of SCI is less dominant in
      affecting the local temperatures in and around muscle cells. In order to test
      this hypothesis, two-dimensional finite element (FE) models of cross sections
      through the microanatomy of muscle tissue were developed using COMSOL
      Multiphysics software for normal and SCI muscles. The models included muscle
      cells, extracellular matrix (ECM), and capillaries, each with its own
      geometrical, thermal, and heat production properties. The SCI model configuration
      specifically included reduced cross section of myofibrils in favor of more ECM,
      less capillaries, and decreased blood inflow rate. After a 20-s heat transfer
      simulation, it was found that temperatures around the cells of the SCI muscle
      were approximately 2 degrees C lower than that in the normal muscle, that is,
      heat production from the muscle cell metabolism did not compensate for the lower
      inflowing blood temperature in the SCI model. We conclude that the temperature
      and rate of inflowing capillary blood are the dominant factors determining the
      localized temperatures in the microarchitecture of an ischemic SCI muscle tissue.
      The altered SCI microanatomy was shown to be less influential. Taken together
      with the Stokes-Einstein theory, our results indicate that diffusivity of
      metabolites would be approximately 50% less around the cells of SCI muscle due to
      local cooling, which is yet another factor compromising tissue viability in the
      patients with SCI.

PMID- 20039143
TI  - BMP depletion occurs during prolonged acid demineralization of bone:
      characterization and implications for graft preparation.
AB  - Demineralization of allograft bone increases the bioavailability of matrix
      associated bone morphogenetic proteins (BMPs), rendering these grafts
      osteoinductive. While osteoinductivity is related to BMP content, little is known
      about how the demineralization protocol, in particular, extended demineralization
      times, affects graft BMP levels. We characterized the BMP-7 content of <710 MUm
      bovine bone powder demineralized under various conditions. Using 1 g of bone per
      50 ml of 0.125 N, 0.25 N, or 0.5 N HCl, demineralization was performed at room
      temperature for 5 min to 24 h. Minimum residual calcium levels were obtained
      within 90 min and were <1 wt % using the 0.25 N and 0.5 N baths and 17 wt % using
      the 0.125 N bath. Measured peak BMP-7 levels were also obtained within 90 min and
      were 161-165 ng g(-1) using the 0.25 N and 0.5 N baths and 55.2 ng g(-1) using
      the 0.125 N bath. This compares to 5.1 ng g(-1) for undemineralized bone. Further
      acid bath exposure to 24 h resulted in BMP-7 decline to about 50% of the peak
      value, which was significant. The BMP-7 half-life was estimated to be 26 h. It is
      likely that the decline was due to diffusion of BMP-7 from the bone matrix into
      the acid. These results suggest the importance of not over demineralizing bone
      grafts and should stimulate further research that can be incorporated into the
      processing methodology followed by tissue banks.

PMID- 20039144
TI  - Alcohol consumption and non-Hodgkin lymphoma survival.
AB  - INTRODUCTION: Epidemiological studies have shown that moderate alcohol drinkers
      have a lower death rate for all causes. Alcohol drinking has also been associated
      with reduced risk of non-Hodgkin lymphoma (NHL). Here, we examined the role of
      alcohol consumption on NHL survival by type of alcohol consumed and NHL subtype.
      METHODS: A cohort of 575 female NHL incident cases diagnosed during 1996-2000 in
      Connecticut was followed-up for a median of 7.75 years. Demographic, clinical,
      and lifestyle information was collected at diagnosis. Survival analyses were
      conducted with Kaplan-Meier methods, and hazard ratios (HR) were estimated from
      Cox Proportional Hazards models. RESULTS: Compared to never drinkers, wine
      drinkers experienced better overall survival (75% vs. 69% five-year survival
      rates, p-value for log-rank test = 0.030) and better disease free survival (70%
      vs. 67% five-year disease-free survival rates, p-value for log-rank test =
      0.049). Analysis by NHL subtype shows that the favorable effect of wine
      consumption was mainly seen for patients diagnosed with diffuse large B-cell
      lymphoma (DLBCL) (wine drinkers for more than 25 years vs. never drinkers: HR =
      0.36, 95% CI 0.14-0.94 for overall survival; HR = 0.38, 95% CI 0.16-0.94 for
      disease-free survival), and the adverse effect of liquor consumption was also
      observed among DLBCL patients (liquor drinkers vs. never drinkers: HR=2.49, 95%
      CI 1.26-4.93 for disease-free survival). CONCLUSIONS: Our results suggest a
      moderate relationship between pre-diagnostic alcohol consumption and NHL
      survival, particularly for DLBCL. The results need to be replicated in larger
      studies. IMPLICATIONS FOR CANCER SURVIVORS: Pre-diagnostic behaviors might impact
      the prognosis and survival of NHL patients.

PMID- 20039145
TI  - Protective effect of fish oil on changes in the activities of membrane-bound
      ATPases and mineral status in experimentally induced myocardial infarction in
      Wistar rats.
AB  - The present study evaluated the protective effect of fish oil in isoproterenol
      induced myocardial infarction in rats. The results of the present study indicate
      that the IPH administration decreases the activities of membrane-bound ATPases
      compared to control animals. Fish oil pretreatment brought about significant
      increase in the activity of these membrane-bound ATPases in IPH (isoproterenol
      hydrochloride)-treated animals. Significant increase in serum potassium level
      with concomitant decrease in the values of sodium, magnesium, and calcium were
      observed in IPH-treated rats compared to control rats, fish oil pretreatment
      reversed these changes to near normal. Significant elevation of sodium and
      calcium levels with concomitant decrease in the levels of potassium and magnesium
      were observed in the myocardial tissue of IPH-administered rats compared to
      control rats, fish oil pretreatment followed by IPH administration brought these
      levels to near normal. The levels of lipid peroxidation (LPO) in both serum and
      tissue were increased in IPH-treated rats compared with control rats, whereas
      pretreatment with fish oil in IPH-treated rats maintained near-normal LPO levels.
      The results of the present study reveals that the pretreatment of fish maintains
      the activities of membrane-bound ATPases and the mineral levels at near normal by
      the inhibition of lipid peroxidation.

PMID- 20039146
TI  - Diminished selenium levels in hemodialysis and continuous ambulatory peritoneal
      dialysis patients.
AB  - In this cross-sectional study, selenium (Se) levels in the sera of 35
      hemodialysis (HD) patients and 34 patients undergoing continuous ambulatory
      peritoneal dialysis (CAPD) for more than 3 months were compared with the serum Se
      levels of 34 healthy volunteers. The observed Se levels of 100.8 +/- 51.9 ug/L in
      the sera of the HD patients and of 65.5 +/- 32.1 ug/L in the sera of the CAPD
      patients were significantly lower than the 134.9 +/- 81.2 ug/L of the controls,
      with p = 0.002 and 0.02, respectively. Furthermore, the Se levels were
      significantly higher in the HD rather than the CAPD patients (p = 0.01). In the
      spent dialysate effluent fluid of 32 of the CAPD patients Se was undetectable, in
      the remaining two CAPD patients the Se levels were 1.9 and 4.6MUg/l,
      respectively. The low Se levels of HD and CAPD patients as compared to healthy
      persons are attributed to diminished Se retention due to chronic oxidative
      stress.

PMID- 20039147
TI  - Anaemia, zinc and copper deficiencies among pregnant women in central Sudan.
AB  - Anaemia is a widespread problem in many parts of the world especially in tropic
      areas. Among pregnant women, it has negative consequences on maternal and
      perinatal outcomes. A cross-sectional study was conducted to investigate the
      prevalence of anaemia, iron, zinc and copper deficiencies among pregnant women in
      Wad Medani hospital, central Sudan and to examine the relationship of these
      micronutrients with haemoglobin (Hb) levels. One hundred four (52.5%) out of 200
      pregnant women had anaemia (Hb < 11 gm/dl) and 3 (1.5) % had severe anaemia (Hb <
      7 gm/dl). Iron deficiency (S-ferritin < 15 ug/l), iron deficiency anaemia (<11
      gm/dl and S-ferritin < 15 ug/l) were prevalent in 25 (12.5%) and 13 (6.5%) of
      these women, respectively. Ninety (45.0%) and eight (4.0%) of these women had
      zinc (<80 ug/ml) and copper (<80 ug/ml) deficiency, respectively. In 24 (12.0%)
      of these women, there were >=2 deficiencies of these elements. S-copper was not
      [corrected] significantly lower in patients with anaemia. While age, parity,
      gestational age, ferritin, zinc and copper were not predictors for anaemia, women
      who practiced pica were at higher risk for anaemia (OR = 3.4, 95% CI = 1.4-7.9, P
      = 0.004). Gestational age was significantly inversely correlated with haemoglobin
      (r = 0.161, P = 0.03), S-ferritin (r = 0.285, P = 0.001) and S-zinc (r = 0.166, P
      = 0.02). Thus, dietary and supplement interventions are required to prevent and
      control anaemia in this setting. Further research is needed.

PMID- 20039148
TI  - The effect of iron treatment on adhesion molecules in patients with iron
      deficiency anemia.
AB  - The present study was aimed to determine the effect of iron supplementation on
      levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble
      vascular cell adhesion molecule-1 (sVCAM-1) in patients with iron deficiency
      anemia (IDA). In this study, 26 female patients diagnosed with iron deficiency
      were treated approximately 3 months of oral iron supplementation (99 +/- 10 days;
      ferrous glycine sulfate; 100 mg/day of elemental iron). Levels of sICAM-1 and
      sVCAM-1 were assessed prior to treatment and after approximately 3 months of
      treatment and compared with 26 healthy female subjects. A significant increase in
      sVCAM levels was found in the patients with iron deficiency at the end of the
      treatment relative to pretreatment levels compared to controls, whereas no
      significant differences were determined in sICAM levels. In the posttreatment
      period, no significant change was observed in sICAM levels compared to the
      pretreatment levels, whereas sVCAM levels decreased. However, after the treatment
      period, the sVCAM, hemoglobin, mean corpuscular volume (MCV), and serum ferritin
      levels did not return to the normal range compared to the controls. Pretreatment
      sVCAM-1 levels were inversely correlated with levels of hemoglobin, hemotocrit,
      MCV, serum iron, and ferritin. After treatment, the sVCAM-1 levels were
      negatively correlated with ferritin levels. Levels of sVCAM were significantly
      higher in patients with IDA than controls. After the treatment period, the sVCAM
      levels were not completely normalized in patients with IDA compared to controls,
      regardless of the presence of inadequate levels of hemoglobin, MCV, and serum
      ferritin. Thus, iron supplementation not only ameliorates anemia, but may also
      reduce the inflammation markers in cases with IDA.

PMID- 20039149
TI  - Serum electrolyte and mineral variations during pregnancy and lactation in Nili
      Ravi buffalo.
AB  - The aim of present study was to determine the changes of sodium, potassium,
      chloride, copper, and zinc in serum of Nili-Ravi buffalo during pregnancy and
      lactation. The study was carried out on 25 Nili-Ravi buffaloes during March 2008
      to February 2009 at Buffalo Research Institute, Pattoki, District Kasur. Blood
      samples were taken from each buffalo during early pregnancy (Phase EP), i.e.,
      between 1 and 3 months gestation, mid pregnancy (Phase MP), i.e., between 4 and 6
      months gestation, late pregnancy (Phase LP), i.e., between 7 and 10 months
      gestation, and during lactation (Phase LT). Serum sodium, potassium, and chloride
      were determined on a clinical chemistry analyzer whereas copper and zinc were
      determined on an atomic absorption spectrophotometer. The mean serum sodium,
      potassium, and chloride concentrations varied non-significantly (P > 0.05) during
      pregnancy and lactation. With advancing pregnancy, copper increased and was
      significantly high (P < 0.05) during late pregnancy whereas during lactation
      copper concentrations dropped significantly (P < 0.05). The zinc concentrations
      increased non-significantly during early and mid pregnancy. There were
      significant differences (P < 0.05) in zinc concentrations during lactation
      compared with late pregnancy. This study demonstrates that concentrations of
      serum sodium, potassium, and chloride remain unchanged during pregnancy and
      lactation whereas serum copper concentrations increased and zinc concentrations
      decreased with advancing pregnancy because of the demand of the fetus at
      different periods of pregnancy.

PMID- 20039150
TI  - Adding calcium scoring to myocardial perfusion imaging: Does it alter physicians'
      therapeutic decision making?

PMID- 20039151
TI  - Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal
      subjects and patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Measuring the rate of clearance of carbon-11 labelled acetate from
      myocardium using positron emission tomography (PET) is an accepted technique for
      noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake
      of [(11)C]acetate, however, is related to myocardial blood flow (MBF) and several
      tracer kinetic models for quantifying MBF using [(11)C]acetate have been
      proposed. The objective of this study was to assess these models. METHODS:
      Eighteen healthy subjects and 18 patients with hypertrophic cardiomyopathy (HCM)
      were studied under baseline conditions with [(11)C]acetate and [(15)O]water. Four
      previously reported methods, including single- and multi-tissue compartment
      models, were used to calculate MBF from the measured [(11)C]acetate rate of
      influx K (1) and the (previously) reported relationship between K (1) and MBF.
      These MBF values were then compared with those derived from corresponding
      [(15)O]water studies. RESULTS: For all models, correlations between
      [(11)C]acetate and [(15)O]water-derived MBF ranged from .67 to .86 (all P < .005)
      in the control group and from .73 to .85 (all P < .001) in the HCM group. Two out
      of four models systematically underestimated perfusion with [(11)C]acetate,
      whilst the third model resulted in an overestimation. The fourth model, based on
      a simple single tissue compartment model with spillover, partial volume and
      recirculating metabolite corrections, resulted in a regression equation with a
      slope of near unity and an Y-intercept of almost zero (controls, K(1) = .74[MBF]
      + .09, r = .86, SEE = .13, P < .001 and HCM, K(1) = .89[MBF] + .03, r = .85, SEE
      = .12, P < .001). CONCLUSION: [(11)C]acetate enables quantification of MBF in
      fairly good agreement with actual MBF in both healthy individuals and patients
      with HCM. A single tissue compartment model with standardized correction for
      recirculating metabolites and with corrections for partial volume and spillover
      provided the best results.

PMID- 20039153
TI  - Anatomical variations in the tendon sheath of the first compartment.
AB  - Using Hiranuma's classification, we carefully examined anatomical variations in
      the first compartments of 246 human wrist joints from 124 cadavers. Morphological
      examinations were conducted to determine the number of accessory tendons and the
      existence of dissepiments for the extensor pollicis brevis (EPB) and abductor
      pollicis longus (APL) tendons. Anatomical variations of EPBs and APLs were
      grouped together by type, and appearance ratios were calculated based on
      Hiranuma's classification. Of the 246 wrist joints, 156 were categorized as
      normal type (63.4%), 57 as complete dissepiment type (23.2%), 22 as incomplete
      dissepiment type (8.9%), and 11 as EPB-lacking type (4.5%). Accessory tendons
      were identified in both the EPB and the APL tendons of most cadavers, and the
      incidence of dissepiment in tendon sheaths was approximately 33%. Sixty-six of
      the 193 wrist joints (34.2%) showed equal numbers of right and left accessory
      tendons. However, the number of EPB accessory tendons was higher than in previous
      studies, and in all cases some kind of dissepiment was observed in the APL and
      EPB. The number of EPB and APL accessory tendons showed no clear differences by
      gender, age, or right and left specificity.

PMID- 20039152
TI  - Optical molecular imaging in atherosclerosis.
AB  - Current imaging techniques focus on evaluating the anatomical structure of blood
      vessel wall and atherosclerotic plaque. These techniques fail to evaluate the
      biological processes which take place in the vessel wall and inside the plaque.
      Novel imaging techniques like optical imaging can evaluate the biological and
      cellular processes inside the plaque and provide information which can be vital
      for better patient risk stratification. This review highlights the various
      optical imaging techniques and their application in assessing biological
      processes in atherosclerosis.

PMID- 20039154
TI  - Estrogen modulates central and peripheral responses to cold in female rats.
AB  - The aim of this study was to determine whether estrogen modulates central and
      peripheral responses to cold in female rats. In ovariectomized female rats with
      and without administered estrogen [E(2) (+) and E(2) (-), respectively], the
      counts of cFos-immunoreactive cells in the medial preoptic nucleus (MPO) and
      dorsomedial hypothalamic nucleus (DMH) in the hypothalamus were greater in the
      E(2) (+) rats than in the E(2) (-) rats at 5 degrees C. Examination of the
      response of normal female rats to exposure to 5 degrees C at different phases of
      the estrus cycle revealed that counts of cFos-immunoreactive cells in the MPO,
      DMH, and posterior hypothalamus and the level of uncoupling protein 1 mRNA in the
      brown adipose tissues were greater in the proestrus phase than on day 1 of the
      diestrus phase. This result was linked to the level of plasma estrogen. The body
      temperature during cold exposure was higher in the E(2) (+) rats than in the E(2)
      (-) rats and was also higher in the proestrus phase than on day 1 of the diestrus
      phase. We conclude that estrogen may affect central and peripheral responses
      involved in thermoregulation in the cold.

PMID- 20039156
TI  - From death to recovery following hypoxia ischemia: if TGFbeta is a central
      regulator, is integrin beta8 the switch?

PMID- 20039155
TI  - Association of metallothionein-III with oligodendroglial cytoplasmic inclusions
      in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is an adult-onset neurodegenerative disease
      characterised by Parkinsonian and autonomic symptoms and by widespread
      intracytoplasmic inclusion bodies in oligodendrocytes. These glial cytoplasmic
      inclusions (GCIs) are comprised of 9-10 nm filaments rich in the protein alpha
      synuclein, also found in neuronal inclusion bodies associated with Parkinson's
      disease. Metallothioneins (MTs) are a class of low-molecular weight (6-7 kDa),
      cysteine-rich metal-binding proteins the expression of which is induced by heavy
      metals, glucocorticoids, cytokines and oxidative stress. Recent studies have
      shown a role for the ubiquitously expressed MT-I/II isoforms in the brain
      following a variety of stresses, whereas, the function of the brain-specific MT
      isoform, MT-III, is less clear. MT-III and MT-I/II immunostaining of post-mortem
      tissue in MSA and normal control human brains showed that the number of MT-III
      positive cells is significantly increased in MSA in visual cortex, whereas MT
      I/II isoforms showed no significant difference in the distribution of
      immunopositive cells in MSA compared to normal tissue. GCIs were immunopositive
      for MT-III, but were immunonegative for the MT-I/II isoforms. Immunofluorescence
      double labelling showed the co-localisation of alpha-synuclein and MT-III in GCIs
      in MSA tissue. In isolated GCIs, transmission electron microscopy demonstrated MT
      III immunogold labelling of the amorphous material surrounding alpha-synuclein
      filaments in GCIs. High-molecular weight MT-III species in addition to MT-III
      monomer were detected in GCIs by Western analysis of the detergent-solubilised
      proteins of purified GCIs. These results show that MT-III, but not MT-I/II, is a
      specific component of GCIs, present in abnormal aggregated forms external to the
      alpha-synuclein filaments.

PMID- 20039157
TI  - [Burden of disease and level of patient's medical care in substitution treatment
      for opiates].
AB  - BACKGROUND AND PURPOSE: Within the framework of an interdisciplinary cooperation,
      the authors set up an on-site medical service provider in a specialized methadone
      substitution center in Germany. Here, they report on the prevalence of infectious
      and noninfectious diseases, and the vaccination status of substituted heroin
      dependent patients. PATIENTS AND METHODS: All patients who visited the medical
      care service provider between February 2008 and December 2008 were included in
      this study. RESULTS: Ten patients (7%) were seropositive for the hepatitis A
      virus. Two patients (1.3%) suffered from chronic hepatitis B; 40 patients (27%)
      were cured after a hepatitis B infection. Additionally, 99 patients (68%) were
      infected with hepatitis C virus (HCV), and 41 patients (28%) had active hepatitis
      C. Furthermore, 48 hepatitis C patients (33%) were cured. Of those, 25 patients
      (17%) cleared the virus spontaneously and 23 (16%) after ribavirin/interferon
      combination therapy. Ten (7%) of 146 patients were infected with the human
      immunodeficiency virus (HIV). Of those, four patients had active hepatitis C, and
      five patients were cured after a hepatitis C infection. 18 patients (12%) were
      vaccinated against hepatitis A and 28 (19%) against hepatitis B. Two of the 41
      patients with chronic hepatitis C were vaccinated against hepatitis A. The most
      frequent noninfectious diagnoses were arterial hypertension (n = 28), bronchial
      asthma (n = 8), and diffuse liver parenchymal damage (n = 12). CONCLUSION: These
      results emphasize that i.v. drug users on substitution therapy are an underserved
      collective with a high prevalence of disease. The challenge consists in
      facilitating this population access to internistic and infectious disease
      service. The offer of an on-site medical service was well accepted. This is
      essential for an ongoing reduction of HIV and HCV prevalence in the drug users.

PMID- 20039158
TI  - [Doping in disabled sports. Doping control activities at the Paralympic Games
      1984-2008 and in Germany 1992-2008].
AB  - Activities concerning the fight against doping with regard to the Paralympic
      Games have been initiated in 1984, when first doping controls were conducted. The
      foundation of the International Paralympic Committee exactly 20 years ago (1989)
      considerably supported systematic sports drug-testing programs specifically
      designed to meet the particular challenges related to disabled sports, which
      yielded a variety of adverse analytical findings (e.g., with anabolic steroids,
      diuretics, corticosteroids, and stimulants) especially at Paralympic Summer
      Games. In Germany, doping controls for handicapped athletes were established in
      1992 and have been conducted since by the National Paralympic Committee Germany
      and the National Anti-Doping Agency. Also here, various analogies in terms of
      antidoping rule violations were found in comparison to doping controls of
      nondisabled athletes. In the present article, available numbers of samples
      analyzed at Paralympic Summer and Winter Games as well as within the doping
      control program for disabled sports in Germany are summarized, and
      particularities concerning sample collection and the doping method termed
      boosting are presented.

PMID- 20039159
TI  - [Central Patients Admission (CPA) unit--connecting inpatient and outpatient
      care].
AB  - BACKGROUND: Due to the novel reimbursement policies, hospitals face substantial
      conflicts regarding best patient care and optimal utilization of resources. In
      order to optimize patient treatment, a central patients admission (CPA) unit has
      been established. METHODS: All patients electively referred to the hospital were
      primarily treated by a medical specialist at the CPA unit. According to an
      appropriateness evaluation protocol established with the medical service of the
      health insurances of Bavaria ("MDK-Bayern"), patients were treated as inpatients
      or outpatients. The impact of this novel admission procedure was assessed for a
      period of 30 months. RESULTS: Within 30 months following establishment of the CPA
      unit, 10% of the patients were treated as outpatients, whereas 90% of referred
      patients were admitted as inpatients. Nonetheless, numbers of inpatients
      increased by 20.7% after 24 months compared to 12 months following establishment
      of the CPA unit with a substantial increase of patients referred by external
      medical specialists. In addition, there were no cases of inappropriate admission.
      CONCLUSION: The CPA unit is an ideal instrument for treating patients cross
      sectorally as well as more effectively and economically advocating
      reorganization. Establishment of a CPA unit leads to greater satisfaction among
      patients, referring physicians, and medical staff.

PMID- 20039160
TI  - [Hereditary hemochromatosis].
AB  - Genetic hemochromatosis is classified into four subtypes of which only type 1 is
      of clinical importance in Caucasians. Type 1 is due to an autosomal recessive
      inborn error of metabolism; the homozygous C282Y mutation of the HFE gene on
      chromosome 6 accounts for more than 90% of the clinical phenotype in populations
      of Celtic origin. The mutation leads to an inadequately high intestinal iron
      absorption which may finally cause iron overload in and damage to various organs.
      Type 2 is the juvenile form of iron overload which leads to a severe phenotype
      prior to age 30 with cardiomyopathy and hypogonadism. The corresponding mutations
      are located in the hemojuveline and hepcidin genes. Typ 3 has mainly been
      described in Italian families and refers to mutations in transferrin receptor 2
      gene. Histopathologic and clinical consequences of type 3 hemochromatosis are
      similar to those seen in type 1. Types 2 and 3 are autosomal recessive traits.
      Type 4 hemochromatosis follows an autosomal dominant trait; the corresponding
      mutation affects the basolateral iron carrier ferroportin 1. Diagnosis of
      hemochromatosis is based on determinations of serum ferritin and transferrin
      saturation with the latter being more sensitive and specific. In case of a
      homozygous C282Y gene test, liver biopsy is not required for diagnosis. Liver
      biopsy is, however, recommended in C282Y homozygotes at ferritin values > 1,000
      ng/ml because of an increased risk for liver fibrosis. Phlebotomy treatment is
      the standard care to remove iron in genetic hemochromatosis. Patients treated in
      the early noncirrhotic stage have a normal life expectancy. Thus, future efforts
      should aim at early diagnosis. Iron removal also improves the outcome in
      cirrhotic patients. Liver carcinoma may develop in cirrhotic patients despite
      iron depletion. Liver cancers without cirrhosis are so rare that screening is
      only recommended in cirrhotic patients.

PMID- 20039161
TI  - [Uhl's disease--rare cause of chronic right heart failure].
AB  - BACKGROUND: Uhl's disease is a rare disorder characterized by aplasia of the
      right ventricular myocardium leading to its parchment-like appearance. The loss
      of right ventricular function causes massive dilation of the right heart with
      progressive right heart failure in severe cases. CASE REPORT: A 70-year-old
      patient with progressive dyspnea and massive peripheral edema presented with an
      acute decompensation of chronic right heart failure. Previously, pulmonary
      arterial hypertension was suspected and therapy with sildenafil was initiated.
      Echocardiography and cardiac MRI (magnetic resonance imaging) showed marked
      hypoplasia of the right ventricular free wall and marked dilation of the right
      heart without pulmonary arterial hypertension. The diagnosis of Uhl's disease was
      confirmed by typical MRI morphology. A slow cardiac recompensation was achieved
      by medicinal treatment of heart insufficiency. Hence the patient remained stable
      for 9 months with medicinal therapy without signs of further decompensation.
      CONCLUSION: Uhl's disease should be suspected in patients with massive right
      heart dilation without pulmonary hypertension even in the adult. The major
      diagnostic clue is hypoplasia of the right ventricular free wall, which can be
      demonstrated by echocardiography and cardiac MRI. There is no causal therapy for
      the disease. Besides medicinal therapy for heart failure, right ventricular
      cardiomyoplasty and, ultimately, transplantation might be undertaken
      successfully.

PMID- 20039162
TI  - [Current DRG: each creature it's procedure].

PMID- 20039164
TI  - [Targeted diagnosis of mesenteric ischemia].

PMID- 20039167
TI  - Weathering and dissolution rates among Pb shot pellets of differing elemental
      compositions exposed to various aqueous and soil conditions.
AB  - The present study was performed to investigate the weathering and dissolution
      rates of Pb shot pellets differing in elemental composition (Pb, Sb, and As)
      exposed under various aqueous and soil conditions using five commercial shot
      pellet preparations. Upon immersion in distilled water, the dissolution rates of
      shot pellets, calculated from the difference in weight before versus after
      immersion, decreased with increasing Sb + As contents and the dominant
      precipitate was hydrocerussite. These subsidiary ingredients may be related to
      the difficulty of metallic Pb oxidation (transformation to PbO). Weight losses
      standardized by the amount of rainfall upon exposure to rainfall on open
      grassland and under canopies of Japanese cedar (Cryptomeria japonica) and bamboo
      leafed oak (Quercus myrsinaefolia) were 1.11, 1.07, and 7.35 mg g pellets(-1)
      year(-1) L(-1), respectively, and was also related to Sb + As contents in shot
      pellets. However, annual dissolution rates of Pb standardized by the amount of
      rainfall as the soluble fraction at the same sites were 0.72, 0.33, and 0.40 mg
      Pb g pellets(-1) year(-1) L(-1) in the same order. These trends seemed to be
      related to the rainfall pH, which induces precipitation of Pb dissolved as
      PbCO(3) under conditions of higher pH at the Q. myrsinaefolia site or organic
      matter released from leaves, etc., which can form metal complexes. Dissolution
      rates of shot pellets buried in soils (Cambisol, Fluvisol, Regosol, Andosol) also
      seemed to be related to the soil pH and dissolved organic matter contents but
      were about sixfold faster than those with exposure to rainfall.

PMID- 20039168
TI  - Comparison of bulk sediment and sediment elutriate toxicity testing methods.
AB  - Numerous methods exist for assessing the potential toxicity of sediments in
      aquatic systems. In this study, the results from 10-day bulk sediment toxicity
      test methods using Hyalella azteca and Chironomus tentans were compared to
      results from 96-h Pimephales promelas and Ceriodaphnia dubia renewed acute
      toxicity tests conducted using elutriate samples prepared from the same
      sediments. The goal of the study was to determine if the results from the
      elutriate tests were comparable to those obtained from the bulk sediment tests.
      Of the 25 samples analyzed, 16 were found to be toxic to at least one of the
      species tested, in either elutriate or bulk sediment tests. The C. tentans 10-day
      bulk sediment test was the most sensitive, with 12 sediment samples exhibiting
      toxicity to this species, whereas the H. azteca bulk sediment test and C. dubia
      96-h elutriate test were the least sensitive, exhibiting toxicity in only 7 of
      the 25 sediments tested. The P. promelas elutriate test found 8 of the 25
      sediments to be toxic. Based on the total number of sites found to show toxicity,
      results from testing indicate 96-h elutriate tests show a level of sensitivity
      comparable to 10-day bulk sediment tests in assessing toxicity quantitatively.
      However, the methods did not always find toxicity at the same sites, suggesting
      that the ability of elutriate tests to predict toxicity (quantitatively) is not
      statistically correlated with bulk sediment methods. This would indicate that a
      suite of toxicity test methods would provide the most complete measure of site
      condition; however, in circumstances where bulk sediment testing is not feasible,
      elutriate tests can provide a practical and credible alternative for toxicity
      assessment.

PMID- 20039169
TI  - Cloning and nucleotide sequences of carbazole degradation genes from marine
      bacterium Neptuniibacter sp. strain CAR-SF.
AB  - The marine bacterium Neptuniibacter sp. strain CAR-SF utilizes carbazole as its
      sole carbon and nitrogen sources. Two sets of clustered genes related to
      carbazole degradation, the upper and lower pathways, were obtained. The marine
      bacterium genes responsible for the upper carbazole degradation pathway, carAa,
      carBa, carBb, and carC, encode the terminal oxygenase component of carbazole 1,9a
      dioxygenase, the small and large subunits of the meta-cleavage enzyme, and the
      meta-cleavage compound hydrolase, respectively. The genes involved in the lower
      degradation pathway encode the anthranilate dioxygenase large and small subunit
      AntA and AntB, anthranilate dioxygenase reductase AntC, 4-oxalocrotonate
      tautomerase, and catechol 2,3-dioxygenase. Reverse transcription-polymerase chain
      reaction confirmed the involvement of the isolated genes in carbazole
      degradation. Escherichia coli cells transformed with the CarAa of strain CAR-SF
      required ferredoxin and ferredoxin reductase for biotransformation of carbazole.
      Although carAc, which encodes the ferredoxin component of carbazole 1,9a
      dioxygenase, was not found immediately downstream of carAaBaBbC, the carAc-like
      gene may be located elsewhere based on Southern hybridization. This is the first
      report of genes involved in carbazole degradation isolated from a marine
      bacterium.

PMID- 20039170
TI  - Co-existence of multidrug-resistant and -susceptible strains of Pseudomonas
      aeruginosa from a single clinical isolate.
AB  - Pseudomonas aeruginosa is a leading cause of hospital-acquired infections and
      difficult to treat due to acquired-resistance to multiple antibiotics. A pair of
      strains, M38100A and M38100B, previously identified from a single clinical
      isolate of P. aeruginosa was investigated to understand phenotypic and genotypic
      characteristics. Results revealed that the pair of strains was very similar for
      serum susceptibility, growth rate in a complex medium (Luria-Bertani), RAPD
      genotype profiles, status of genes encoding type III secretion toxins, and no
      extra-chromosomal DNA. However, antibiotic susceptibility of the strain M38100B
      showed resistant to all tested-antibiotics while the strain M38100A showed
      susceptible to the same tested-antibiotics as similar levels of P. aeruginosa
      PAO1. The strain M38100B exhibited no growth in a minimal medium as a sole carbon
      and nitrogen source of glutamate while the strain M38100A grew well in the same
      minimal medium. These results suggest that multidrug resistance of the strain
      M38100B may be caused by multiple mutations on its genomic DNA and a precursor
      stage for a homogeneous multidrug resistant population.

PMID- 20039171
TI  - Churg-Strauss syndrome: retrospective study in Burgundian population in France in
      past 10 years.
AB  - Churg-Strauss Syndrome (SCS) is a systemic vasculitis associated with asthma and
      eosinophilia. The aim of our work is to describe this pathology in the Burgundian
      population in France. We counted from the hospitalisation data-processing
      summaries, the whole of the SCS hospitalised in Burgundy between 1998 and 2008.
      During the follow-up, the clinical and paraclinical characteristics of every
      patient were collected. The average prevalence is of 11.3 per million inhabitants
      and the incidence is of 1.2 new cases per million inhabitants per annum. There
      exists however, a great prevalence disparity and incidence amongst the various
      departments of the area. The patient's average follow-up is of 7.7 years. In 23%
      of the cases one finds a starting factor for vasculitis. The delay between the
      first signs and the diagnostic is an average of 61 months. The ANCA are positive
      in 26% of cases and of anti-myeloperoxidase specificity in 83% of cases (P <
      0.001). The most profitable biopsies are essentially cutaneous and neuromuscular.
      At the diagnostic, two-third of the patients have had a treatment adapted
      according to the current recommendations based on the Five Factor Score. The
      remission rate within a 1-year period is of 77%. The remission is strongly
      correlated to the therapeutic protocol associating corticoids and
      cyclophosphamide (P < 0.05). In conclusion, the prevalence of SCS in our area is
      similar to that observed in other European regions. However, this vasculitis
      remains a difficult and often a tardive diagnostic pathology.

PMID- 20039172
TI  - Effect of the long-term administration of nebivolol on clinical symptoms,
      exercise capacity and left ventricular function in patients with heart failure
      and preserved left ventricular ejection fraction: background, aims and design of
      the ELANDD study.
AB  - BACKGROUND: The SENIORS trial demonstrated that nebivolol has beneficial effects
      in patients with heart failure. However, the role of beta-blocker therapy in
      patients with heart failure and preserved left ventricular ejection fraction
      (HFPEF) is still unsettled. OBJECTIVE: To assess the long-term effects of
      administration of nebivolol, compared to placebo, on the clinical symptoms,
      exercise capacity and parameters of left ventricular (LV) function in patients
      with HFPEF. METHODS: The Effect of Long-term Administration of Nebivolol on
      clinical symptoms, exercise capacity and left ventricular function in patients
      with Diastolic Dysfunction (ELANDD) study is a prospective multicenter European
      trial in 120 patients with HFPEF randomised to nebivolol or placebo. HFPEF is
      defined as symptoms or signs of heart failure, a LV ejection fraction >45% and
      evidence of diastolic LV dysfunction by Doppler echocardiography. Procedures
      include a baseline clinical examination, 6-min walk test (6MWT),
      electrocardiography, Doppler echocardiography and Minnesota QoL questionnaire.
      Nebivolol or placebo is started at 2.5 mg/day and gradually uptitrated to 10
      mg/day. After initiation of the study, patients are assessed at 1, 2, 5 and 6
      weeks (titration phase) and at weeks 12 and 26. The primary endpoint is the
      change from baseline in the 6MWT distance with nebivolol versus placebo. Sample
      size calculations are based on an anticipated 15% difference (70 m) in the 6MWT
      distance between nebivolol and placebo-treated patients. This study will allow
      the collection of data regarding the possible clinical benefits and the effects
      on LV function of nebivolol administration in patients with HFPEF.

PMID- 20039173
TI  - Severe left main coronary stenosis and mitral regurgitation in a young female
      patient without cardiovascular risk factors 14 years after mediastinal radiation
      therapy.

PMID- 20039174
TI  - Oxidative stress induced by loss of Cu,Zn-superoxide dismutase (SOD1) or
      superoxide-generating herbicides causes axonal degeneration in mouse DRG
      cultures.
AB  - Axonal degeneration is a common pathologic feature in peripheral neuropathy,
      neurodegenerative disease, and normal aging. Oxidative stress may be an important
      mechanism of axonal degeneration, but is underrepresented among current
      experimental models. To test the effects of loss of the antioxidant enzyme Cu,Zn
      superoxide dismutase (SOD1) on axon survival, we cultured dorsal root ganglion
      (DRG) neurons from SOD1 knockout mice. Beginning as early as 48-72 h, we observed
      striking degeneration of Sod1-/- axons that was prevented by introduction of
      human SOD1 and was attenuated by antioxidant treatment. To test susceptibility to
      increased superoxide production, we exposed wild-type DRGs to the redox-cycling
      herbicides paraquat and diquat (DQ). Dose-dependent axon degeneration was
      observed, and toxicity of DQ was exacerbated by SOD1 deficiency. MTT staining
      suggested that DRG axons are more susceptible to injury than their parent cell
      bodies in both paradigms. Taken together, these data demonstrate susceptibility
      of DRG axons to oxidative stress-mediated injury due to loss of SOD1 or excess
      superoxide production. These in vitro models provide a novel means of
      investigating oxidative stress-mediated injury to axons, to improve our
      understanding of axonal redox control and dysfunction in peripheral neuropathy.

PMID- 20039175
TI  - Standard chemoradiation versus intensity-modulated chemoradiation: a quality of
      life assessment in oropharyngeal cancer patients.
AB  - This study is based on the context that many patients with advanced oropharyngeal
      carcinoma are being treated with primary chemoradiation. The aims of this study
      are to identify differences in quality of life (QOL) between patients with
      advanced oropharyngeal cancer following traditional chemoradiation versus
      chemotherapy with intensity-modulated radiation therapy (CIMRT). This research is
      designed on a cohort study from an academic tertiary referral center. Fifty
      patients were identified from an institutional database of patients who had
      undergone primary chemotherapy and radiation (traditional or IMRT) for advanced
      oropharyngeal carcinoma. Patients responded via mail using the University of
      Washington quality of life instrument version 4. Statistical analysis of data was
      performed using Chi-square and Wilcoxon tests. The results comprise the responses
      of 17 CRT (57%) and 14 CIMRT (70%) patients. The patients completed the survey
      between 9 and 44 months following end of treatment. When adjusted for tumor stage
      and time since treatment, CIMRT patients reported improved appearance (p = 0.05),
      chewing (p = 0.02), and mood (p = 0.01). There was a trend toward significance
      for improved activity (p = 0.07), recreation (p = 0.07), and anxiety (p = 0.08).
      There were no differences between the two groups for saliva, taste, shoulder
      function, speech, and swallowing. But there was a trend for significance for
      improved overall QOL in patients who had undergone CIMRT (p = 0.06). In
      conclusion, CIMRT results in improved QOL for some domains but surprisingly not
      for swallowing or saliva. Patients undergoing CIMRT also report slightly better
      QOL overall when compared to patients receiving more traditional forms of
      radiation therapy.

PMID- 20039176
TI  - Differential rates of proliferation and apoptosis in nasal polyps correspond to
      alterations in DNA spatial distribution and nuclear polarization as observed by
      confocal microscopy.
AB  - The study aimed to investigate the expression of p53, Bcl-2 and Ki-67 in relation
      to the histologic and nuclear qualitative and spatial characteristics of chronic
      rhinosinusitis with polyposis (CRP). Imprint smears obtained from surgically
      removed nasal polyps of 20 patients were studied. The polyps were classified
      according to their histological characteristics as: hyperplasia (simple and
      pronounced) and squamous metaplasia. The expression of p53, Bcl-2 and Ki-67 was
      assessed by immunocytochemistry. DNA spatial distribution and nuclear orientation
      were studied by staining with propidium iodide and examined by confocal
      microscopy. Positive immunoreaction for p53, Ki-67 and Bcl-2 was observed in 50,
      65, and 50% of polyp's smears, respectively. For each diagnosis, the rates were
      simple hyperplasia 60, 80 and 30%, pronounced hyperplasia 80, 100 and 40%,
      metaplasia 0, 0 and 100%, respectively. Abnormal chromatin distribution and
      nuclear disorientation was observed in three cases of pronounced hyperplasia
      combined with positive immunoreaction for Ki-67 and p53 and negative
      immunoreaction for Bcl-2. CRP demonstrated different proliferation and apoptotic
      rates, according to their histology. Nuclear characteristics observed by confocal
      microscopy are associated with the immunocytochemical markers of proliferation
      and apoptosis.

PMID- 20039177
TI  - Association of work related chronic stressors and psychiatric symptoms in a Swiss
      sample of police officers; a cross sectional questionnaire study.
AB  - PURPOSE: (1) To identify work related stressors that are associated with
      psychiatric symptoms in a Swiss sample of policemen and (2) to develop a model
      for identifying officers at risk for developing mental health problems. METHOD:
      The study design is cross sectional. A total of 354 male police officers answered
      a questionnaire assessing a wide spectrum of work related stressors. Psychiatric
      symptoms were assessed using the "TST questionnaire" (Langner in J Health Hum
      Behav 4, 269-276, 1962). Logistic regression with backward procedure was used to
      identify a set of variables collectively associated with high scores for
      psychiatric symptoms. RESULTS: A total of 42 (11.9%) officers had a high score
      for psychiatric symptoms. Nearly all potential stressors considered were
      significantly associated (at P < 0.05) with a high score for psychiatric
      symptoms. A significant model including 6 independent variables was identified:
      lack of support from superior and organization OR = 3.58 (1.58-8.13), self
      perception of bad quality work OR = 2.99 (1.35-6.59), inadequate work schedule OR
      = 2.84 (1.22-6.62), high mental/intellectual demand OR = 2.56 (1.12-5.86), age
      (in decades) OR = 1.82 (1.21-2.73), and score for physical environment complaints
      OR = 1.30 (1.03-1.64). CONCLUSIONS: Most of work stressors considered are
      associated with psychiatric symptoms. Prevention should target the most frequent
      stressors with high association to symptoms. Complaints of police officers about
      stressors should receive proper consideration by the management of public
      administration. Such complaints might be the expression of psychiatric caseness
      requiring medical assistance. Particular attention should be given to police
      officers complaining about many stressors identified in this study's multiple
      model.

PMID- 20039178
TI  - Precocious pollen germination in Arabidopsis plants with altered callose
      deposition during microsporogenesis.
AB  - Pollination is essential for seed reproduction and for exchanges of genetic
      information between individual plants. In angiosperms, mature pollen grains
      released from dehisced anthers are transferred to the stigma where they become
      hydrated and begin to germinate. Pollen grains of wild-type Arabidopsis thaliana
      do not germinate inside the anther under normal growth conditions. We report two
      Arabidopsis lines that produced pollen grains able to in situ precociously
      germinate inside the anther. One of them was a callose synthase 9 (cs9) knockout
      mutant with a T-DNA insertion in the Callose Synthase 9 gene (CalS9). Male
      gametophytes carrying a cs9 mutant allele were defective and no homozygous
      progeny could be produced. Heterozygous mutant plants (cs9/+) produced
      approximately 50% defective pollen grains with an altered male germ unit (MGU)
      and aberrant callose deposition in bicellular pollen. Bicellular pollen grains
      germinated precociously inside the anther. Another line, a transgenic plant
      expressing callose synthase 5 (CalS5) under the CaMV 35S promoter, also contained
      abnormal callose deposition during microsporogenesis and displaced MGUs in pollen
      grains. We also observed that precocious pollen germination could be induced in
      wild-type plants by incubation with medium containing sucrose and calcium ion and
      by wounding in the anther. These results demonstrate that precocious pollen
      germination in Arabidopsis could be triggered by a genetic alteration and a
      physiological condition.

PMID- 20039179
TI  - Systematic analysis of GT factor family of rice reveals a novel subfamily
      involved in stress responses.
AB  - GT factors constitute a plant-specific transcription factor family with a
      conserved trihelix DNA-binding domain. In this study, comprehensive sequence
      analysis suggested that 26 putative GT factors exist in rice. Phylogenetic
      analysis revealed three distinctive subfamilies (GTalpha, GTbeta, and GTgamma) of
      plant GT factors and each subfamily has a unique composition of predicted motifs.
      We characterized the OsGTgamma-1 gene, a typical member of the GTgamma subfamily
      in rice. This gene encodes a protein containing a conserved trihelix domain, and
      the OsGTgamma-1:GFP fusion protein was targeted to nuclei of rice cells. The
      transcript level of OsGTgamma-1 was strongly induced by salt stress and slightly
      induced by drought and cold stresses and abscisic acid treatment. Two other
      members of the GTgamma subfamily, OsGTgamma-2 and OsGTgamma-3, were also induced
      by most of the abiotic stresses. These results suggested that the genes of the
      GTgamma subfamily in rice may be involved in stress responses. A homozygous
      mutant osgtgamma-1 (with T-DNA inserted in the promoter region of OsGTgamma-1)
      showed more sensitive to salt stress than wild-type rice. Overexpression of
      OsGTgamma-1 in rice enhanced salt tolerance at the seedling stage. This evidence
      suggests that the OsGTgamma subfamily may participate in the regulation of stress
      tolerance in rice.

PMID- 20039182
TI  - Vascular smooth muscle contraction/relaxation of rat carotid artery is not
      altered by bone grafting substitutes in vitro.
AB  - PURPOSE: The aim of this study was to explore the effects of various bone
      grafting substitutes (Osteosponge, Perioglas, Tutoplast, and Surgibone) on
      vascular smooth muscle tonus. METHODS: Bilateral carotid arteries were removed
      from rats and contraction/relaxation of isolated vessel rings were measured
      before and after contact with the biomaterials and then, for dose-dependent
      epinephrine and papaverin administrations, by a force displacement transducer.
      The data of each biomaterial group were collected by a computerized system and
      corresponding software at a sample rate of 1,000 kHz and were converted to
      contraction force. RESULTS: Vascular contraction forces were influenced in
      response to biomaterials tested except for Osteosponge (P < 0.05), although the
      differences between groups were insignificant (P > 0.05). There was a dose
      dependent vascular response to epinephrine and papaverine administration upon
      biomaterial contact (P < 0.05). The dose-dependent vascular responses to
      epinephrine and papaverine administration were almost similar for all
      biomaterials tested (P < 0.05), suggesting that the biomaterials led to
      reversible effects on vascular contraction/relaxation behavior, which resulted in
      recovery. CONCLUSIONS: Osteosponge, Perioglas, Tutoplast, and Surgibone do not
      alter vascular smooth muscle tonus and vitality and therefore would, presumably,
      not jeopardize the angiogenesis of fresh blood vessels and full vascularization
      during tissue healing.

PMID- 20039180
TI  - Regulatory divergence of the duplicated chromosomal loci sox11a/b by
      subpartitioning and sequence evolution of enhancers in zebrafish.
AB  - We used the classic example of the duplicated zebrafish sox11a and -b loci to
      test the duplication, degeneration, complementation (DDC) model of genome
      evolution through whole genome duplication. While recent reports have
      demonstrated sub-partitioning of regulatory sequences in duplicated regions, a
      comparison of the regulatory capabilities of extant regulatory sequences derived
      from ancient ancestral elements has been scarce. Consistent with the DDC model,
      we find that ancestral regulatory elements distributed over several hundred kb
      were lost in either one or the other zebrafish duplicate, leading to
      subpartitioning. However, regulatory sequences kept as duplicates near both sox11
      co-orthologs diverged in sequence from each other and from human elements and in
      the regulatory patterns they drive in transgenic zebrafish. Evolutionary analysis
      of the loci suggested that both zebrafish protein coding sox11 orthologs have
      been maintained by purifying selection, and have evolved at comparable rates,
      indicative of non-diverged protein functions. The duplicated regulatory elements,
      conversely, evolved with different divergence rates and degrees of
      subfunctionalization. These data show that regulatory evolution of gene
      expression patterns occurred both through differential loss as well as through
      regulatory sequence evolution in zebrafish versus human genomes.

PMID- 20039184
TI  - Protective role of moderate alcohol drinking in systemic lupus erythematosus.

PMID- 20039181
TI  - Polycomb group gene function in sexual and asexual seed development in
      angiosperms.
AB  - In sexually reproducing angiosperms, double fertilization initiates seed
      development, giving rise to two fertilization products, the embryo and the
      endosperm. In the endosperm, a terminal nutritive tissue that supports embryo
      growth, certain genes are expressed differentially depending on their parental
      origin, and this genomic imbalance is required for proper seed formation. This
      parent-of-origin effect on gene expression, called genomic imprinting, is
      controlled epigenetically through histone modifications and DNA methylation. In
      the sexual model plant Arabidopsis, the Polycomb group (PcG) genes of the plant
      Fertilization Independent Seed (FIS)-class control genomic imprinting by
      specifically silencing maternal or paternal target alleles through histone
      modifications. Mutations in FIS genes can lead to a bypass in the requirement of
      fertilization for the initiation of endosperm development and seed abortion. In
      this review, we discuss the role of the FIS complex in establishing and
      maintaining genomic imprinting, focusing on recent advances in elucidating the
      expression and function of FIS-related genes in maize, rice, and Hieracium, and
      particularly including apomictic Hieracium species that do not require paternal
      contribution and thus form seeds asexually. Surprisingly, not all FIS-mediated
      functions described in Arabidopsis are conserved. However, the function of some
      PcG components are required for viable seed formation in seeds formed via sexual
      and asexual processes (apomixis) in Hieracium, suggesting a conservation of the
      seed viability function in some eudicots.

PMID- 20039185
TI  - The effect of synthetic retinoid, Am80, on T helper cell development and antibody
      production in murine collagen-induced arthritis.
AB  - Retinoids are known to promote T helper (Th)2 and regulatory T cell (Treg)
      differentiation, and suppress Th1 and Th17 in vitro. Am80, a synthetic retinoid,
      is reported to ameliorate collagen-induced arthritis (CIA). The aims of this
      study are to determine the effects of Am80 on CIA in detail, and on Th
      development and antibody (Ab) production in vivo. Murine CIA was induced by
      immunization with bovine type II collagen (CII) at days 1 and 22. Treatment with
      Am80 from day 1 to 35 significantly lowered clinical arthritis score, suppressed
      cellular infiltration and bone destruction in the joint, decreased interleukin
      (IL)-17 and increased interferon (IFN)-gamma production by CII-stimulated
      splenocytes, and decreased proportion of Foxp3(+) splenic CD4 T cells and serum
      anti-CII Ab levels. Thus, Am80 inhibited Th17 and Treg and enhanced Th1
      differentiation in vivo. In contrast, Am80 applied from day 15 to 35 did not
      alter arthritis score, IL-17 or IFN-gamma production by CII-stimulated
      splenocytes, but decreased the proportion of Foxp3(+) splenic CD4 T cells and
      serum anti-CII Ab levels. Am80 exhibits inhibitory effects on CIA and might
      regulate both Th development and Ab production in vivo. Decreased Th17 by
      treatment with Am80 might be responsible for the attenuation of arthritis.

PMID- 20039183
TI  - Leveling the field in the treatment of rheumatoid arthritis with biologic
      therapies: equal access for equal efficacy.

PMID- 20039186
TI  - A case of post-streptococcal reactive arthritis in which lesions were detected
      with [18F]-fluorodeoxyglucose positron emission tomography-CT imaging and
      magnetic resonance imaging.
AB  - A 55-year-old man with lumbago and polyarthralgia was admitted to our hospital.
      Laboratory data showed elevated levels of anti-streptolysin O and C-reactive
      protein. Throat swab culture revealed beta-hemolytic streptococcal infection.
      Magnetic resonance imaging detected effusion of the lumbar bone and the left hip
      joint. Positron emission tomography-computed tomography (PET-CT) demonstrated
      increased fluorodeoxyglucose activity in the bilateral shoulder and hip joints
      and the interspinal ligament between L2 and L3. He was diagnosed as having post
      streptococcal reactive arthritis (PSReA) and treated with amoxicillin hydrate.
      Polyarthralgia improved and did not relapse. To our knowledge, no results of PET
      CT have previously been reported in patients with PSReA. We propose that PET-CT
      might be a useful tool for diagnosing PSReA.

PMID- 20039187
TI  - Investigation of pathological and clinical features of lupus nephritis in 73
      autopsied cases with systemic lupus erythematosus.
AB  - The aims of this study were to analyze the clinical and pathological features of
      lupus nephritis (LN) and examine the association between these features and
      pathological condition, treatment, and prognosis. Of the 177 systemic lupus
      erythematosus patients who died while receiving inpatient care at Juntendo
      University Hospital between 1960 and 2001, we investigated the clinical features,
      treatment, and pathological features of 73 of these who underwent pathological
      autopsy and had a clear medical history. We divided these cases into two groups,
      i.e., those up to 1979 (Group A) and those during and after 1980 (Group B) in
      order to investigate changes in tendencies by age. We also divided the cases into
      three groups by time interval between diagnosis and death to investigate long
      term prognosis. Uremia was the direct cause of death in 38.9% of cases in Group A
      and only 10.8% of cases in Group B. Pathological features showed a tendency to
      change to a sclerotic lesion as the duration of the disorder became longer.
      Uremia attributable to LN was the direct cause of death in relatively fewer
      cases, although it is still found in the majority of LN cases and remains a
      problem requiring stringent management. The treatment of sclerotic lesions may be
      an issue that needs further attention.

PMID- 20039188
TI  - Expression of Thermobifida fusca thermostable raw starch digesting alpha-amylase
      in Pichia pastoris and its application in raw sago starch hydrolysis.
AB  - A gene encoding the thermostable raw starch digesting alpha-amylase in
      Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into Pichia
      pastoris X-33 host strain using the vector pGAPZalphaA, allowing constitutive
      expression and secretion of the protein. Recombinant expression resulted in high
      levels of extracellular amylase production, as high as 510 U/l in the Hinton
      flask culture broth. The purified amylase showed a single band at about 65 kDa by
      SDS-polyacrylamide gel electrophoresis after being treated with endo-beta-N
      acetylglycosaminidase H, and this agrees with the predicted size based on the
      nucleotide sequence. About 75% of the original activity remained after heat
      treatment at 60 degrees C for 3 h. The optimal pH and temperature of the purified
      amylase were 7.0 and 60 degrees C, respectively. The purified amylase exhibited a
      high level of activity with raw sago starch. After 48-h treatment, the DPw of raw
      sago starch obviously decreased from 830,945 to 378,732. The surface of starch
      granules was rough, and some granules displayed deep cavities.

PMID- 20039189
TI  - Technological properties of bakers' yeasts in durum wheat semolina dough.
AB  - Properties of 13 Saccharomyces cerevisiae strains isolated from different sources
      (traditional sourdoughs, industrial baking yeasts etc.) were studied in dough
      produced with durum wheat (Sicilian semolina, variety Mongibello). Durum wheat
      semolina and durum wheat flour are products prepared from grain of durum wheat
      (Triticum durum Desf.) by grinding or milling processes in which the bran and
      germ are essentially removed and the remainder is comminuted to a suitable degree
      of fineness. Acidification and leavening properties of the dough were evaluated.
      Strains isolated from traditional sourdoughs (DSM PST18864, DSM PST18865 and DSM
      PST18866) showed higher leavening power, valuable after the first and second
      hours of fermentation, than commercial baking yeasts. In particular the strain
      DSM PST 18865 has also been successfully tested in bakery companies for the
      improvement of production processes. Baking and staling tests were carried out on
      five yeast strains to evaluate their fermentation ability directly and their
      resistance to the staling process. Amplified fragment length polymorphism (fAFLP)
      was used to investigate genetic variations in the yeast strains. This study
      showed an appreciable biodiversity in the microbial populations of both wild and
      commercial yeast strains.

PMID- 20039190
TI  - Bacterial assay for the rapid assessment of antifouling and fouling release
      properties of coatings and materials.
AB  - An assay has been developed to accurately quantify the growth and release
      behaviour of bacterial biofilms on several test reference materials and coatings,
      using the marine bacterium Cobetia marina as a model organism. The assay can be
      used to investigate the inhibition of bacterial growth and release properties of
      many surfaces when compared to a reference. The method is based upon the staining
      of attached bacterial cells with the nucleic acid-binding, green fluorescent SYTO
      13 stain. A strong linear correlation exists between the fluorescence of the
      bacterial suspension measured (RFU) using a plate reader and the total bacterial
      count measured with epifluorescence microscopy. This relationship allows the
      fluorescent technique to be used for the quantification of bacterial cells
      attached to surfaces. As the bacteria proliferate on the surface over a period of
      time, the relative fluorescence unit (RFU) measured using the plate reader also
      shows an increase with time. This was observed on all three test surfaces (glass,
      Epikote and Silastic T2) over a period of 4 h of bacterial growth, followed by a
      release assay, which was carried out by the application of hydrodynamic shear
      forces using a custom-made rotary device. Different fixed rotor speeds were
      tested, and based on the release analysis, 12 knots was used to provide standard
      shear force. The assay developed was then applied for assessing three different
      antifouling coatings of different surface roughness. The novel assay allows the
      rapid and sensitive enumeration of attached bacteria directly on the coated
      surface. This is the first plate reader assay technique that allows estimation of
      irreversibly attached bacterial cells directly on the coated surface without
      their removal from the surface or extraction of a stain into solution.

PMID- 20039191
TI  - Enhancing functional expression of heterologous lipase B in Escherichia coli by
      extracellular secretion.
AB  - Functional expression of recombinant Pseudozyma antarctica lipase B (PalB) in
      Escherichia coli has been technically problematic due to protein misfolding,
      ineffective disulfide bond formation, and protein instability associated with
      intracellular proteolysis. To overcome these problems, an alternative approach
      was explored in this study by extracellular secretion of PalB via two Sec
      independent secretion systems, i.e., the alpha-hemolysin (type I) and the
      modified flagellar (type III) secretion systems, which can export proteins of
      interest from the cytoplasm directly to the exterior of the cell. Both shaker
      flask and bioreactor cultivations were performed to characterize the developed
      PalB expression/secretion systems. Bioactive PalB was expressed and secreted
      extracellularly either as a HlyA fusion (i.e., PalB-HlyA via type I system) or an
      intact protein (via type III system). However, the secretion intermediates in the
      intracellular fraction of culture samples were non-bioactive even though they
      were soluble, suggesting that the extracellular secretion did mediate the
      development of PalB activity. Also importantly, the secretion strategy appeared
      to have a minimum impact on cell physiology. PalB secretion via the type I system
      was fast with higher specific PalB activities but poor cell growth. On the other
      hand, the secretion via the type III system was slow with lower specific PalB
      activities but effective cell growth.

PMID- 20039192
TI  - Sarcoma metastatic to the brain: a series of 35 cases and considerations from 27
      years of experience.
AB  - The authors report their 27-year experience regarding 35 cases of supratentorial
      brain metastasis from sarcoma treated in a single institution: these included ten
      osteosarcomas, seven leiomyosarcomas, five Ewing sarcomas, four malignant fibrous
      histiocytomas, three alveolar soft-part sarcomas (ASPS), two rhabdomyosarcomas,
      one liposarcoma, and three unclassified sarcomas. The first 15 cases of the
      series have already been described in a previous publication. Median survival
      after craniotomy was 9.8 months (range: 4-24). In patients with preoperative
      Karnofsky performance score (KPS) > 60 it was 12.8 months (range: 6.5-24 months)
      versus 5.4 months for those patients with a KPS < or = 60 (P = 0.01). Eight
      patients had more than one lesion, six of which were treated in the last ten
      years. Of the three patients with ASPS, the first two were alive at 15 and 20
      months (before being lost to follow-up) whereas the third patient is alive at 24
      month follow-up. The authors conclude that surgery is more effective in treating
      selected patients with sarcoma metastatic to the brain, and that patients with
      metastasis from ASPS have good prognosis when submitted to surgical treatment.
      The complete removal of all brain metastases "en bloc" and a KPS > 60 are
      associated with the best prognosis. Finally, it seems that surgical indications
      for multiple brain metastases from sarcoma have increased during the last ten
      years.

PMID- 20039194
TI  - Bulimic eating disorders in primary care: hidden morbidity still?
AB  - The current study examined the features of women with bulimic-type eating
      disorders (n = 24) attending primary care in two smaller urban regions of the
      USA. The assessment included measures of eating disorder psychopathology, medical
      comorbidity, impairment in role functioning, potential barriers to treatment and
      actual use of health services. Eating disorders, primarily variants of bulimia
      nervosa and binge eating disorder not meeting formal diagnostic criteria, were
      associated with marked impairment in psychosocial functioning. Although two
      thirds of participants recognized a problem with their eating, less than 40% had
      ever sought treatment from a health professional for an eating or weight problem
      and only one in ten had sought such treatment from a mental health specialist.
      Only one-third had ever been asked about problems with eating by a primary care
      practitioner or other health professional. However, more than 80% had sought
      treatment from a health professional for symptoms of anxiety or depression. Most
      reported some degree of discomfort in discussing eating problems with others, and
      half reported that they would not be truthful about such problems if asked.
      Having an eating disorder was associated with several chronic medical conditions,
      including joint pain, gastrointestinal problems and fatigue. Although the small
      sample size limits any firm conclusions, the findings suggest that the health
      burden of bulimic-type eating disorders is substantial but remains largely
      hidden. Efforts may be needed to improve the eating disorders "mental health
      literacy" of both patients and primary care practitioners in order to facilitate
      early, appropriate intervention.

PMID- 20039193
TI  - The bZIP transcription factor OsABF1 is an ABA responsive element binding factor
      that enhances abiotic stress signaling in rice.
AB  - A number of basic leucine zipper (bZIP) transcription factors are known to
      function in stress signaling in plants but few have thus far been functionally
      characterized in rice. In our current study in rice, we have newly isolated and
      characterized the OsABF1 (Oryza sativa ABA responsive element binding factor 1)
      gene that encodes a bZIP transcription factor. Its expression in seedling shoots
      and roots was found to be induced by various abiotic stress treatments such as
      anoxia, salinity, drought, oxidative stress, cold and abscisic acid (ABA).
      Subcellular localization analysis in maize protoplasts using GFP fusion vectors
      indicated that OsABF1 is a nuclear protein. In a yeast experiment, OsABF1 was
      shown to bind to ABA responsive elements (ABREs) and its N-terminal region was
      necessary to transactivate the downstream reporter gene. The homozygous T-DNA
      insertional mutants Osabf1-1 and Osabf1-2 were more sensitive in response to
      drought and salinity treatments than wild type plants. Furthermore, the
      upregulated expression of some ABA/stress-regulated genes in response to ABA
      treatment was suppressed in these Osabf1 mutants. Our current results thus
      suggest that OsABF1 is involved in abiotic stress responses and ABA signaling in
      rice.

PMID- 20039195
TI  - Evaluating a bilingual video to improve infant feeding knowledge and behavior
      among immigrant Latina mothers.
AB  - Childhood obesity is recognized as a major health problem in the United States
      and is occurring at ever younger ages. While most prevention efforts are aimed at
      school-age children, this project focuses on the caregivers of children from 0 to
      24 months of age. This study is an evaluation of an educational English/Spanish
      infant feeding video, distributed for home viewing at one New York City Special
      Supplemental Food Program for Women, Infants and Children (WIC) center (video
      group) but not at three others (comparison group). Baseline, 3 and 6 month infant
      feeding knowledge and behavior surveys were conducted. For this report, analyses
      are restricted to Latina immigrant mothers. The video and comparison group
      mothers were similar in age, education, and parity. The video group was more
      likely to speak Spanish at home, and had lower knowledge scores at baseline. At
      the 6 month follow-up, knowledge increased for both groups, but the video group
      showed a greater increase in knowledge between baseline and 6 months: in ordered
      logistic regression analyses the video group had a 1.7 times greater score
      increase at each outcome level. The video group also showed positive changes in
      behavior-later age at first solid feeding was observed in the video group. We
      found that an inexpensive, low-intensity video intervention can positively impact
      maternal knowledge and behavior related to infant feeding among immigrant
      Latinas. Attention should be given to intervening early with high-risk
      populations.

PMID- 20039196
TI  - Internet-based support for infertile patients: a randomized controlled study.
AB  - This study aimed to evaluate the efficacy and patient acceptance of the first
      German-language Internet-based treatment for infertile patients. Infertile
      patients (N = 124) were randomly assigned to either an 8-week Internet-based
      cognitive-behavioral treatment, or to a waiting-list control group. Participants
      were assessed at treatment start, post-treatment, and at a 5-month follow-up.
      Outcome measures included mental health and pregnancy rate. From pre- to
      posttest, treated participants in contrast to controls did not show significant
      improvement, although between-group effect sizes were in favor of the
      intervention group on all mental health measures (Cohen's d ranged from 0.16 to
      0.38). The intervention significantly reduced the depression level of clinically
      distressed and depressed participants. No effects were found regarding pregnancy
      rate. The treatment was assessed as positive or very positive by 80% of the
      participants; this finding coupled with the high demand for such support confirm
      that Internet-based interventions are a promising new approach for infertile
      patients that needs more development and testing.

PMID- 20039197
TI  - Hypoalgesia associated with elevated resting blood pressure: evidence for
      endogenous opioid involvement.
AB  - This study used a placebo-controlled, between-subjects opioid blockade design to
      evaluate endogenous opioid involvement in the hypoalgesia associated with
      elevated resting blood pressure (BP) in 163 healthy individuals. Participants
      were randomly assigned to Drug condition (placebo, naltrexone) and Task Order
      (computerized maze task with harassment followed by an ischemic pain task or vice
      versa). Resting BP was assessed, followed by drug administration, and then the
      pain and maze tasks. A significant Drug x Systolic BP (SBP) interaction was
      observed on McGill Pain Questionnaire-Affective pain ratings (P < .01),
      indicating that BP-related hypoalgesia observed under placebo was absent under
      opioid blockade. A significant Gender x Drug x SBP x Task Order interaction was
      observed for VAS pain intensity (P < .02). Examination of simple effects
      comprising this interaction suggested that BP-related hypoalgesia occurred only
      in male participants who experienced the pain task in the absence of emotional
      arousal, and indicated that this hypoalgesia occurred under placebo but not under
      opioid-blockade. Results suggest that under some circumstance, BP-related
      hypoalgesia may have an endogenous opioid-mediated component in healthy
      individuals, particularly men.

PMID- 20039198
TI  - Cumulus cell contact during oocyte maturation in mice regulates meiotic spindle
      positioning and enhances developmental competence.
AB  - PURPOSE: To investigate the role of cumulus cell contact during oocyte maturation
      on meiotic spindle assembly and the acquisition of developmental competence.
      METHODS: Cumulus oocyte complexes isolated from mouse ovaries subjected to in
      vitro or in vivo maturation were analyzed by confocal microscopy with respect to
      oocyte somatic cell contacts and for their ability to develop after parthenogenic
      activation during embryo culture. RESULTS: Cell contact is maintained during
      maturation in vivo, predisposing oocytes to cortical meiotic spindle assembly and
      developmental competence acquisition. In contrast, oocytes matured in vitro lose
      cell contact coincident with central meiotic spindle assembly that results in
      cleavage delays upon egg activation and failure to form blastocysts. Experimental
      disruption of cell contact by the actin-depolymerizing agent latrunculin B
      results in the formation of enlarged meiotic spindles with dispersed chromosomes
      unlike the compact ordering of chromosomes observed on spindles formed after in
      vivo maturation, suggesting a link between cell contact and the acquisition of
      developmental competence. CONCLUSIONS: Somatic cell contact optimizes oocyte
      quality during meiotic maturation by regulating the spatial organization and
      function of the meiotic spindle through actin-dependent mechanisms that enhance
      development.

PMID- 20039200
TI  - Comment on Trujillo-Tiebas MJ et al. J Assist Reprod Genet DOI 10.1007/s10815-009
      9339-1.

PMID- 20039201
TI  - Fractionation and potential mobility of trace metals in Danube alluvial aquifer
      within an industrialized zone.
AB  - Thirty-five alluvial sediments of the River Danube and 12 groundwater samples
      were taken within the Pancevo Oil Refinery (Serbia). The results for groundwater
      samples exceed European primary drinking water standards for Fe (obtained
      results, >200 MUg/l) and Mn (obtained results, >50 MUg/l), while the levels of
      the trace metals are below the thresholds for drinking water quality. Sediments
      were treated by sequential extraction procedure with five different solutions,
      each having a higher extraction capacity than the previous one. We also wanted to
      determine the possible relationships among trace metals and between sediment
      properties and elemental concentrations. These solutions partitioned metals into
      CH(3)COONH(4) extractable (F1); HCl carbonate extractable and NH(2)OH.HCl easily
      reducible (F2); (NH(4))(2)C(2)O(4)/H(2)C(2)O(4) moderately reducible (F3);
      H(2)O(2)-HNO(3) organic/sulfide extractable fractions (F4); and HCl acid-soluble
      residue (F5). The sum of trace metals Ni, Pb, Cu, and Zn associated with the
      first two fractions (exchangeable, carbonate, and easily reducible) is
      significant and extremely important because it represents the proportion of heavy
      metals that can be easily remobilized by changes in environmental conditions such
      as pH, redox potential, salinity, etc. Sediments located nearer the groundwater
      flow are exposed to stronger groundwater fluctuation and had a higher quantity of
      amorphous and less stable substrates of trace metals. Principal component
      analysis was used to understand and visualize the associations between the trace
      metals and certain geological forms within analyzed sediments. The observed
      association between Cr with total sulfur and Mn from the acid-soluble residue
      could indicate that Cr is in the form of reduced, less toxic Cr(III), which is
      from the ecochemical point of view very important.

PMID- 20039202
TI  - Geochemical patterns in soils in and around Siddipet, Medak District, Andhra
      Pradesh, India.
AB  - This paper reports the first results of geochemical survey carried out in and
      around Siddipet, taking soil (topsoil 0-25 cm and subsoil 70-95 cm) as the
      sampling media. The data were obtained in a consistent way from 61 sites. The
      samples were analyzed for 29 elements (As, Ba, Cd, Co, Cr, Cu, F, Mo, Ni, Pb, Rb,
      Se, Sr, Th, U, V, Y, Zn, Zr, Si, Al, Fe, Mn, Mg, Ca, Na, K, Ti, and P) by X-ray
      fluorescence spectrometer, and baseline levels for these elements are presented.
      Results reveal that the correlation between the geochemical patterns in the soils
      developed on different litho-variants is not straight forward, but some general
      trends can be observed. Regional parent materials and pedogenesis are the primary
      factors influencing the concentrations of trace elements while anthropogenic
      activities have secondary influence.

PMID- 20039203
TI  - Seasonal and spatial variation of Yamuna River water quality in Delhi, India.
AB  - Yamuna river pollution has been extensively studied with regard to some selected
      parameters in five locations at Palla, Nizamuddin Midstream, Nizamuddin Quarter
      Stream, Agra Canal Midstream, and Agra Canal Quarter Stream in Delhi, India.
      Seasonal and location-wise variation of pollutants namely dissolve oxygen (DO),
      biochemical oxygen demand (BOD), chemical oxygen demand (COD), total Kjeldahl
      nitrogen (TKN), ammonia (AMM), total coliform and fecal coliform were studied for
      6 years during the period of 2000-2005. The study results revealed the lowest
      level of pollution during monsoon. The statistical analysis revealed a positive
      correlation between DO, BOD, COD, TKN, and AMM.

PMID- 20039204
TI  - Use of biological indicators to assess water quality of the Ul River (Portugal).
AB  - Diatoms and macroinvertebrates have been extensively used as water quality
      indicators in Europe for the last two decades. In Portugal, the use of biological
      indicators to assess water quality in rivers has increased greatly. The aim of
      this work was to assess the water quality and ecological status of the Ul River
      in order to evaluate its ability for the establishment of a fluvial beach, using
      periphytic diatoms and macroinvertebrates as indicators. Four sites were selected
      along the Ul River. At each site, biological, physical, and chemical parameters
      were investigated. Epilithic diatoms and macroinvertebrates were sampled. The
      Specific Polluosensitivity Index and the Biological Diatom Index were applied to
      diatom data, while for macroinvertebrates, the Iberian Biological Monitoring
      Working Party (IBMWP) was used. According to the results obtained, it was
      possible to conclude that up to now, this river does not possess the ideal
      conditions for the establishment of a fluvial beach. We concluded that epilithic
      diatoms and macroinvertebrates provided consistent information on water quality
      assessment and can be used as biological indicators of the water quality in Ul
      River.

PMID- 20039205
TI  - Age-dependent cognitive impairment in a Drosophila fragile X model and its
      pharmacological rescue.
AB  - Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable
      cause of mental retardation worldwide. The overriding clinical manifestation of
      this disease is mild to severe cognitive impairment. Age-dependent cognitive
      decline has been identified in Fragile X patients, although it has not been fully
      characterized nor examined in animal models. A Drosophila model of this disease
      has been shown to display phenotypes bearing similarity to Fragile X symptoms.
      Most notably, we previously identified naive courtship and memory deficits in
      young adults with this model that appear to be due to enhanced metabotropic
      glutamate receptor (mGluR) signaling. Herein we have examined age-related
      cognitive decline in the Drosophila Fragile X model and found an age-dependent
      loss of learning during training. We demonstrate that treatment with mGluR
      antagonists or lithium can prevent this age-dependent cognitive impairment. We
      also show that treatment with mGluR antagonists or lithium during development
      alone displays differential efficacy in its ability to rescue naive courtship,
      learning during training and memory in aged flies. Furthermore, we show that
      continuous treatment during aging effectively rescues all of these phenotypes.
      These results indicate that the Drosophila model recapitulates the age-dependent
      cognitive decline observed in humans. This places Fragile X in a category with
      several other diseases that result in age-dependent cognitive decline. This
      demonstrates a role for the Drosophila Fragile X Mental Retardation Protein
      (dFMR1) in neuronal physiology with regard to cognition during the aging process.
      Our results indicate that misregulation of mGluR activity may be causative of
      this age onset decline and strengthens the possibility that mGluR antagonists and
      lithium may be potential pharmacologic compounds for counteracting several
      Fragile X symptoms.

PMID- 20039206
TI  - Health promotion and education activities of community pharmacists in Kuwait.
AB  - OBJECTIVES: To investigate self-reported practice of pharmacists regarding health
      promotion and education activities, explore the barriers that may limit their
      involvement in health promotion and education, and identify their willingness to
      participate in continuing education programs related to health education.
      SETTING: Community pharmacies in Kuwait. METHOD: A descriptive cross-sectional
      study was performed using a pre-tested questionnaire on a sample of 223 community
      pharmacists. MAIN OUTCOME MEASURES: The extent of the pharmacists' involvement in
      counselling patients about health promotion and education topics, their
      preparation to counsel patients in health promotion and education topics, and
      their perceived success in changing the patients' health behaviour. RESULTS: The
      response rate was 92%. Information on medication use was the most frequent reason
      for consumers seeking community pharmacists' advice. The majority of respondents
      believed that behaviour related to the proper use of drugs was very important.
      There was less agreement on the importance of other health behaviours.
      Respondents indicated they were involved in counselling patients on health
      behaviours related to use of drugs as prescribed/directed, weight management,
      medicine contents and side effects, diet modification and stress reduction, but
      were less involved in counselling on other health behaviours. Respondents'
      perception of themselves as "most prepared" to counsel patients closely reflected
      their involvement. Pharmacists reported high levels of success in helping
      patients to achieve improvements in using their drugs properly compared to low
      levels in changing patients' personal health behaviours. The majority of
      respondents believed that pharmacists had a responsibility for counselling
      consumers on health behaviours (97%, 95% CI 95-99%), and indicated their
      willingness to learn more about health promotion (84%, 78-88%). Lack of
      pharmacists' time was reported by about 58% of respondents as the major barrier
      limiting pharmacists' provision of health promotion. CONCLUSION: The role of
      community pharmacists in health promotion and education is primarily focused on
      pharmaceutical issues rather than health behaviour modification. The majority of
      respondents have a positive attitude towards counseling the population on health
      behaviours and indicated their willingness to learn more about health promotion.

PMID- 20039207
TI  - Are local clinical guidelines useful in promoting rational use of antibiotic
      prophylaxis in caesarean delivery?
AB  - OBJECTIVES: To identify changes in prescribing patterns of antibiotic prophylaxis
      in caesarean delivery after introduction of local clinical guidelines. To
      identify changes in outcomes of prescribing antibiotics following the
      implementation of local clinical guidelines on antibiotic prophylaxis. SETTING:
      University of Belgrade, Medical School, Clinic of Gynaecology and Obstetrics
      "Narodni front" Belgrade, Serbia. METHOD: A quantitative retrospective analysis
      of antibiotic use before (January-June 2005), and following (January-June 2006)
      implementation of guidelines on antibiotic prophylaxis in two wards. Patients who
      underwent caesarean section prior to (261) and following (281) introduction of
      local guidelines, participated in this study. MAIN OUTCOME MEASURES: Drug
      utilization cost presented as the number of DDD/100 bed days/eur, the average
      duration of hospital stay, number of wound infections. RESULTS: There was a
      significant change in prescribing patterns of antibiotic prophylaxis in caesarean
      section following introduction of local guidelines. The use of ceftriaxone,
      amikacin and metronidazole decreased (57.47% vs. 11.74%; 9.19% vs. 4.27%; 61.69%
      vs. 46.26%, respectively). On the other hand, the use of "older" antibiotics such
      as gentamicin, cefuroxime, cefazolin and ampicillin increased (14.56% vs. 29.18%;
      9.2% vs. 17.44%; 9.58% vs. 45.2% and 0% vs. 3.9%, respectively). DDD/100 bed
      days/eur analysis revealed a 47% decrease of total cost for prophylactic
      antibiotic treatment in caesarean section following local guideline
      implementation. In contrast, rate of wound infections and duration of hospital
      stay were not significantly different in both groups. CONCLUSION: In an attempt
      to ensure cost-effective prophylactic use of antibiotics in caesarean delivery,
      local clinical guidelines were introduced. They resulted in changes in
      prescribing patterns of antibiotics. There was a significant decrease in use of
      'third' generation of cephalosporin's whereas the use of "older" antibiotics with
      proven efficacy and safety increased. In contrast, there was no significant
      change in treatment outcomes such as wound infection and average hospital stay.

PMID- 20039208
TI  - Dopamine agonist induced compulsive eating behaviour in a Parkinson's disease
      patient.
AB  - CASE DESCRIPTION: A patient diagnosed with type 2 diabetes mellitus and
      Parkinson's disease developed a compulsive eating disorder when treated with a
      dopamine agonist, pramipexole. The patient had no history of psychiatric
      illnesses and upon the discontinuation of pramipexole his abnormal behavioural
      symptoms were resolved. CONCLUSION: Physicians treating Parkinson's disease
      patients with dopamine replacement therapy should inquire about the development
      of any compulsive behaviours. Although uncommon, many of these non-motor symptoms
      go undiagnosed and can have a detrimental impact on a patient's quality of life.

PMID- 20039210
TI  - Cytoreduction and hyperthermic intraperitoneal chemoperfusion in women with
      heavily pretreated recurrent ovarian cancer.
AB  - BACKGROUND: Limited data are available on the use of cytoreductive surgery with
      hyperthermic intraperitoneal chemoperfusion (HIPEC) in patients with recurrent
      stage III ovarian cancer. METHODS: Patients with recurrent, heavily pretreated
      ovarian cancer were enrolled onto a phase II multimodal protocol consisting of
      extensive cytoreduction followed by HIPEC. RESULTS: Forty-two women were treated
      from October 2002 until January 2009. Chemoperfusion was performed with cisplatin
      in 59% and oxaliplatin in 41% of patients. A macroscopically complete resection
      was achieved in 50% of patients. No mortality occurred, and the major morbidity
      rate was 21%. After a mean follow-up of 21 months, median overall survival (OS)
      was 37 months (95% confidence interval 12.2-61.8) and median progression-free
      survival was 13 months (95% confidence interval 6.9-19.1). In univariate
      analysis, OS was influenced by completeness of cytoreduction, type of
      chemoperfusion drug, nodal status, and tumor grade. In a Cox regression model,
      only completeness of cytoreduction (hazard ratio 0.06-0.8, P=.022) and tumor
      grade (hazard ratio 1.23-12.6, P=.021) were independent predictors of OS.
      CONCLUSIONS: In selected patients with heavily pretreated recurrent ovarian
      cancer, cytoreduction combined with HIPEC may provide a meaningful OS with
      acceptable morbidity. Optimal results are achieved in patients with a
      macroscopically complete resection and biologically favorable disease.

PMID- 20039211
TI  - Anterior Perineal PlanE for Ultralow Anterior Resection of the Rectum (the APPEAR
      Technique): a video demonstration.
AB  - BACKGROUND: Sphincter-saving rectal resections have become commonplace in the
      surgical treatment of malignant rectal pathology. However, restoration of
      gastrointestinal continuity by means of conventional techniques proves
      technically challenging in cases of very low rectal pathology, with resultant
      variable requirements for a permanent stoma. The APPEAR procedure (Anterior
      Perineal PlanE for Ultralow Anterior Resection of the rectum) is a novel
      sphincter-saving resection technique to restore gastrointestinal continuity in
      those who would otherwise require a permanent stoma with conventional abdominal
      resections. It ensures that the distal rectum is excised and the anastomosis is
      constructed under direct vision while simultaneously preserving the anal
      sphincter and its somatic nerve supply in their entirety. INDICATIONS: This
      procedure is indicated in the following instances: proven lower-third rectal
      carcinomas where anatomical restrictions prevent satisfactory rectal dissection
      and/or transection with a potential inadequate distal clearance margin; ileoanal
      pouch formation for ulcerative colitis or familial adenomatous polyposis where
      retained rectal tissue is at risk of future malignancy; short or strictured
      rectal stumps where pelvic dissection is hazardous and thus prevents restoration
      of gastrointestinal continuity. CONCLUSIONS: The APPEAR technique is a feasible
      alternative sphincter-saving procedure to further reduce the requirement of
      permanent stoma in the treatment for ultralow rectal pathology; however, it is
      appreciated that a larger study group with long-term follow-up is required. This
      technique should facilitate laparoscopic rectal resection because large and
      distal tumors can be dissected and excised through the perineal wound, ensuring
      adequate distal clearance and the anastomosis constructed under vision at an
      appropriate level. Furthermore, the requirement for an abdominal incision is
      avoided, improving cosmesis.

PMID- 20039212
TI  - Critical assessment of risk factors for complications after cytoreductive surgery
      and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei.
AB  - BACKGROUND: Cytoreductive surgery (CRS) combined with perioperative
      intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected
      patients with pseudomyxoma peritonei (PMP). However, this aggressive treatment
      modality has been consistently associated with variable rates of perioperative
      mortality between 0% and 18% and morbidity between 30% and 70%. This study
      evaluates the clinical and treatment-related risk factors for perioperative
      morbidity and mortality in PMP patients who underwent CRS and PIC. MATERIALS AND
      METHODS: A total of 145 consecutive CRS and PIC procedures for PMP performed
      between January 1996 and March 2009 were evaluated. The association of 12
      clinical and 20 treatment-related risk factors with grades III and IV/V morbidity
      were assessed by univariable and multivariable analysis. RESULTS: The mortality
      (grade V) rate was 3%. The morbidity rates of grades III and IV were 23% and 22%,
      respectively. Eight factors were associated with grade IV/V morbidity on
      univariable analysis: peritoneal cancer index >or=21 (P = .034), ASA score >or=3
      (P = .003), operation duration >or=10 h (P < .001), left upper quadrant
      peritonectomy procedure (P = .037), colonic resection (P = .012), ostomy (P =
      .005), ileostomy (P = .012), and transfusion >or=6 units (p = 0.011).
      Multivariable analysis showed 2 significant risk factors for grade IV/V
      morbidity: ASA >or= 3 (P = .006) and an operation length >or=10 h (P < .001).
      CONCLUSIONS: CRS and PIC has an acceptable rate of perioperative mortality and
      morbidity in selected patients with PMP. Patients with bulky disease who undergo
      a long operation are at a particularly high risk of a severe adverse event.

PMID- 20039213
TI  - Computer-based learning module and the educational process for women with breast
      cancer who desire reconstruction.

PMID- 20039214
TI  - Stage and microscopic positive margins in the treatment of patients with gastric
      cancer.

PMID- 20039215
TI  - Microscopic evaluation of lymph-node-bearing tissue in early-stage cervical
      cancer: a dual-institution review.
AB  - OBJECTIVE: We compared two different methods of microscopic lymph node
      examination of cervical cancer radical hysterectomy specimens to ascertain which
      method translates into higher nodal counts and improved detection of nodal
      metastasis, at M. D. Anderson Cancer Center (MDACC) and the University of North
      Carolina (UNC). METHODS: We retrospectively reviewed the records of 155 patients
      with early-stage cervical cancer who underwent open radical hysterectomy and
      pelvic lymph node dissection from 2000 to 2006. At MDACC lymph nodes were grossly
      dissected from submitted adipose tissue surgical specimens and then
      microscopically examined. At UNC, grossly detected lymph nodes and the remaining
      adipose tissue were microscopically examined. Data regarding clinicopathologic
      features and lymph node dissection were available for all patients. RESULTS: No
      differences in stage, grade or histology were noted between the two centers. The
      median age and body mass index were both higher at MDACC (40 versus 36 years of
      age; 28 versus 26 mg/m(2); P < 0.05) The median lymph node count was lower at
      MDACC (16 versus 23; P = 0.001). By multivariate analysis, UNC evaluation was
      associated with higher total lymph node count (P = 0.001). However, no
      significant difference was noted between institutions in proportion of patients
      with nodal metastases (MDACC 20.3%; UNC 13.5%; P = 0.47). CONCLUSION: The UNC
      method of microscopically examining the entire adipose tissue sample may be
      associated with higher nodal count at open radical hysterectomy. Higher nodal
      count, however, may not translate into increased identification of nodal
      metastases.

PMID- 20039216
TI  - Computer-based learning module increases shared decision making in breast
      reconstruction.
AB  - BACKGROUND: Shared decision making (SDM) combines evidence-based medicine with
      individual patient preferences. Patients who are actively engaged in their own
      health care management with their physicians have been shown to experience not
      only increased compliance, but also higher satisfaction and better outcomes. We
      hypothesize that a computer-based learning module for breast reconstruction
      increases patient involvement in the decision-making process. MATERIALS AND
      METHODS: Women who underwent either immediate or delayed breast reconstruction at
      an academic teaching hospital from 2004 to 2007 were identified. Patients meeting
      inclusion criteria were mailed questionnaires on demographics, informational
      resources, and decision-making processes. Questionnaire results were divided into
      2 groups for analysis: patients who received a standard surgeon consultation and
      patients who were shown a computer-based decision aid in addition to the standard
      consultation. RESULTS: There were 358 women eligible for our study. A total of
      255 patients (75.9%) responded to the survey; 168 patients were shown the
      computer-based decision aid and 87 patients were not. Patients who used the
      computer-based learning module reported a greater role in choosing the type of
      reconstruction (P < .001). Additionally, these patients reported a greater number
      of reconstructive options offered to them (P < .001) and were more satisfied with
      the amount of information provided by their reconstructive surgeon (P = .049).
      CONCLUSIONS: A computer-based learning module allows patients to assimilate
      information and actively participate in choosing type of breast reconstruction.
      Use of this educational modality represents a simple and effective way to improve
      the shared decision-making process.

PMID- 20039217
TI  - The evolving role of taurolidine in cancer therapy.
AB  - BACKGROUND AND DESIGN: Taurolidine consists of two taurinamide rings derived from
      the naturally occurring amino acid taurine. It has been utilized to prevent
      adhesions, as an antimicrobial, and as an anti-inflammatory agent. More recently,
      it has been found to exert antineoplastic activity. We reviewed the literature
      regarding taurolidine and its role in cancer treatment. RESULTS AND CONCLUSION:
      Taurolidine induces cancer cell death through a variety of mechanisms. Even now,
      all the antineoplastic pathways it employs are not completely elucidated. It has
      been shown to enhance apoptosis, inhibit angiogenesis, reduce tumor adherence,
      downregulate proinflammatory cytokine release, and stimulate anticancer immune
      regulation following surgical trauma. Apoptosis is activated through both a
      mitochondrial cytochrome-c-dependent mechanism and an extrinsic direct pathway. A
      lot of in vitro and animal data support taurolidine's tumoricidal action.
      Taurolidine has been used as an antimicrobial agent in the clinical setting since
      the 1970s and thus far appears nontoxic. The nontoxic nature of taurolidine makes
      it a favorable option compared with current chemotherapeutic regimens. Few
      published clinical studies exist evaluating the role of taurolidine as a
      chemotherapeutic agent. The literature lacks a gold-standard level 1 randomized
      clinical trial to evaluate taurolidine's potential antineoplastic benefits.
      However, these trials are currently underway. Such randomized control studies are
      vital to clarify the role of taurolidine in modern cancer treatment.

PMID- 20039218
TI  - Enhancement the prediction of postoperative survival in gastric cancer by
      combining the negative lymph node count with ratio between positive and examined
      lymph nodes.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of the negative
      lymph node (NLN) count on the prognostic prediction of the ratio between positive
      and examined lymph nodes (RML) in gastric cancer after curative resection.
      METHODS: The positive and negative node counts were determined for 456 patients
      who underwent curative resection for gastric cancer. Overall survival was
      examined according to clinicopathologic variables. The correlation between the
      NLN count and the aforementioned best variable for prediction the disease
      specific overall survival was examined. RESULTS: The NLN count cutoffs were
      designed as 0-9, 10-14, and > or =15, with the 5-year survival rate 4.1, 30.7,
      and 74.8%, respectively. RML of 98 patients who had an NLN count of nine or fewer
      was > or =40%. The median survival of these patients was 12 months. Of 88
      patients who had 10 to 14 NLN count, 7 had 74-month median survival with 0.1-10%
      RML, 52 had 47-month median survival with 10.1-40% RML, and 29 had 22-month
      median survival with >40% RML. Of 270 patients who had > or =15 NLN count, 157
      had 114-month median survival without positive nodes, 62 had 98-month median
      survival with 0.1-10% RML, 45 had 40-month median survival with 10.1-40% RML, and
      6 had 14-month median survival with >40% RML. CONCLUSIONS: The NLN count is a key
      factor for improvement of survival prediction of RML in gastric cancer.

PMID- 20039219
TI  - Evaluation of cochlear nerve size by magnetic resonance imaging in elderly
      patients with sensorineural hearing loss.
AB  - PURPOSE: We aimed to determine any differences, if present, between the cross
      sectional area of the cochlear nerve (CN) of elderly patients with sensorineural
      hearing loss (SNHL) and of young patients with normal hearing. MATERIALS AND
      METHODS: The study group included ten patients with age-related SNHL. Fourteen
      volunteer individuals with normal hearing were recruited as the control group. T1
      weighted, T2-weighted and parasagittal three-dimensional Fourier transformation
      constructive interference in steady state (3DFT-CISS) reconstruction images of
      all cases were evaluated. Images were examined for any abnormality of CN. The
      data obtained for each ear with clinical, radiological and audiometric
      examinations were evaluated. RESULTS: The mean CN cross-sectional area was
      measured as 0.0252 cm(2) in the control group, whereas that in the SNHL group was
      0.0232 cm(2). Although speech discrimination scores showed significant
      differences, no statistically significant difference was observed for the CN
      cross-sectional area (p=0.0616). Likewise, there was no difference in CN calibre
      between male and female patients. CONCLUSIONS: The 3DFT-CISS sequence yields
      superior results in CN imaging. Acquired SNHL may not present with significant
      changes in CN size on magnetic resonance imaging (MRI).

PMID- 20039220
TI  - Colorful drying.
AB  - Drying is one of the standard unit operations in the pharmaceutical industry and
      it is important to become aware of the circumstances that dominate during the
      process. The purpose of this study was to test microcapsulated thermochromic
      pigments as heat indicators in a fluid bed drying process. The indicator powders
      were manually granulated with alpha-lactose monohydrate resulting in three
      particle-size groups. Also, pellets were coated with the indicator powders. The
      granules and pellets were fluidized in fluid bed dryer to observe the progress of
      the heat flow in the material and to study the heat indicator properties of the
      indicator materials. A tristimulus colorimeter was used to measure CIELAB color
      values. Color indicator for heat detection can be utilized to test if the heat
      sensitive API would go through physical changes during the pharmaceutical drying
      process. Both the prepared granules and pellets can be used as heat indicator in
      fluid bed drying process. The colored heat indicators give an opportunity to
      learn new aspects of the process at real time and could be exploded, for example,
      for scaling-up studies.

PMID- 20039222
TI  - Guidelines to the Practice of Anesthesia Revised Edition 2010.
AB  - OVERVIEW: The Guidelines to the Practice of Anesthesia Revised Edition 2010 (the
      guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which
      reserves the right to determine their publication and distribution. Because the
      guidelines are subject to revision, updated versions are published annually.
      Whereas previous versions of the guidelines appeared as special supplements to
      the Canadian Journal of Anesthesia (the Journal), this edition of the guidelines
      is published within the Journal. This allows for improved archiving and online
      access to complement the printed version-a new offering for CAS members and
      Journal subscribers. The Guidelines to the Practice of Anesthesia Revised Edition
      2010 supersedes all previously published versions of this document. Although the
      CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to
      ensure high-quality patient care, the society cannot guarantee any specific
      patient outcome. Each anesthesiologist should exercise his or her own
      professional judgement in determining the proper course of action for any
      patient's circumstances. The CAS assumes no responsibility or liability for any
      error or omission arising from the use of any information contained in its
      Guidelines to the Practice of Anesthesia.

PMID- 20039221
TI  - Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal
      anesthesia.
AB  - PURPOSE: Midazolam has only sedative properties. However, dexmedetomidine has
      both analgesic and sedative properties that may prolong the duration of sensory
      and motor block obtained with spinal anesthesia. This study was designed to
      compare intravenous dexmedetomidine with midazolam and placebo on spinal block
      duration, analgesia, and sedation in patients undergoing transurethral resection
      of the prostate. METHODS: In this double-blind randomized placebo-controlled
      trial, 75 American Society of Anesthesiologists' I and II patients received
      dexmedetomidine 0.5 microg . kg(-1), midazolam 0.05 mg . kg(-1), or saline
      intravenously before spinal anesthesia with bupivacaine 0.5% 15 mg (n = 25 per
      group). The maximum upper level of sensory block and sensory and motor regression
      times were recorded. Postoperative analgesic requirements and sedation were also
      recorded. RESULTS: Sensory block was higher with dexmedetomidine (T 4.6 +/- 0.6)
      than with midazolam (T 6.4 +/- 0.9; P < 0.001) or saline (T 6.4 +/- 0.8; P <
      0.001). Time for sensory regression of two dermatomes was 145 +/- 26 min in the
      dexmedetomidine group, longer (P < 0.001) than in the midazolam (106 +/- 39 min)
      or the saline (97 +/- 27 min) groups. Duration of motor block was similar in all
      groups. Dexmedetomidine also increased the time to first request for
      postoperative analgesia (P < 0.01 compared with midazolam and saline) and
      decreased analgesic requirements (P < 0.05). The maximum Ramsay sedation score
      was greater in the dexmedetomidine and midazolam groups than in the saline group
      (P < 0.001). CONCLUSION: Intravenous dexmedetomidine, but not midazolam,
      prolonged spinal bupivacaine sensory blockade. It also provided sedation and
      additional analgesia.

PMID- 20039225
TI  - [Do they understand Morgellons disease?].

PMID- 20039226
TI  - [Guidelines and recommendations on the expert opinions of occupational disease].

PMID- 20039227
TI  - ["15 questions on..."].

PMID- 20039229
TI  - ["Help Conference", a new social assistance for integration according to S 53 SGB
      XII--a two-year analysis].
AB  - OBJECTIVE: To deal with applications for social assistance for integration
      according to S 53 SGB XII, in the district of Hannover a so called "Help
      Conference" was introduced. Since implementation of "Help Conferences", the
      number of applications has increased by about 1,100% over the past five years. We
      analysed whether a change from the institutional help system to more individual
      "help" has already been realised. METHODS: "Help Conferences" recorded between
      2005 and 2006 were evaluated in regard to demographic and medical data. 78 of 202
      protocols (40%) had been filled in completely and thus could be included in our
      evaluation. RESULTS: 37 patients (47%) had F2 spectrum diagnoses according to ICD
      10. More than one third of our patients (31 patients=40%) were male patients with
      a diagnosis of addiction, whereas in this study female patients were rarely
      affected by addiction (5 patients=6%). The first application was filed by the
      hospital social service in most cases. Applications submitted by the patients
      themselves were an exception. 46 applications (59%) were follow-ups, submitted by
      the institution responsible for the patient. CONCLUSIONS: The new system is
      focused on the individual interests of patients and implicates an improved and
      more predictable aftercare in patients with psychiatric diseases.

PMID- 20039230
TI  - Prevalence and MDCT characteristics of asymptomatic Bochdalek hernia in adult
      population.
AB  - PURPOSE: To determine the frequency of asymptomatic incidental Bochdalek hernias
      in adults, using multidetector computed tomography (MDCT), and to ascertain any
      possible relationship between Bochdalek hernia and age, gender, or body mass
      index (BMI). MATERIALS AND METHODS: Seven hundred and forty-eight abdominal, and
      602 chest MDCT scans, which had been performed for a variety of reasons on 1350
      adults, were investigated retrospectively. Location and size of Bochdalek hernias
      seen on these scans were correlated with age, gender, and BMI. On the basis of
      BMI, patients with Bochdalek hernia were classified as group A (BMI < 25) and
      group B (BMI > or =25). RESULTS: A total of 171 Bochdalek hernias were identified
      in 142 of 1350 patients, ranging in age from 25 to 90 years (median age, 57.2),
      representing a prevalence of 10.5%. Sixty leftsided unilateral Bochdalek hernias
      (42.2%), 53 (37.4%) rightsided unilateral Bochdalek hernias, and 29 (20.4%)
      bilateral Bochdalek hernias were detected. Forty-five (31.6%) were categorized as
      small, 82 (57.8%) were medium-sized, and 15 (10.5%) were large. BMI was < 25 in
      62 patients (43.7%), and > or =25 in 80 patients (56.3%). Fourteen patients
      (9.9%) were young adults, while 86 (60.6%) were middle aged, and 42 (29.6%) were
      elderly. No statistically significant relationship was found between dimensions
      or hernia locations and age, gender, or BMI of patients with Bochdalek hernia.
      CONCLUSION: In view of the high prevalence of Bochdalek hernia in our study
      (10.5%), the multiplanar and reconstruction features of MDCT seem to facilitate
      the diagnosis of asymptomatic incidental Bochdalek hernia. No relationship was
      found between asymptomatic incidental Bochdalek hernia and age, gender, or BMI in
      adults.

PMID- 20039231
TI  - Transformation of the maxillary bone in adults with nasal polyposis: a CT
      morphometric study.
AB  - PURPOSE: Nasal polyposis (NP) in adult population is a common problem in
      otorhinolaryngology outpatient practice. Computed tomography (CT) is the ideal
      imaging method to investigate paranasal sinus diseases. There is yet no study in
      the literature measuring the morphometry of maxillary bone in NP. The objectives
      of this study are to correlate the airway variables obtained by CT findings of
      both chronic nasal airway obstruction and control group in an adult population,
      and to investigate whether the bony structure of the airway is affected or not.
      MATERIALS AND METHODS: Forty NP cases that were followed up for 1-5 years by an
      otorhinolaryngologist were included in this retrospective study. Forty subjects
      who had normal findings reported on paranasal CT scans were randomly selected
      from our CT database as the control group. Maxillary and palatine bones (PB) were
      evaluated: the plane angle between the maxillary alveolar processes (MAP) and PB,
      and depth of the maxillary arch of both groups were compared. RESULTS: The mean
      angle between MAP and PB plane was wider in the NP group (right 128.1 +/- 8.5
      degrees and left 126.2 +/- 8.5 degrees ) than control group (right 106.6 +/- 8.1
      degrees and left 105.5 +/- 7.3 degrees). The mean depth of maxillary arch was
      significantly smaller in the NP group (1.2 +/- 0.2 cm) than in the control group
      (1.4 +/- 0.2 cm). CONCLUSION: There could be a relationship between nasal
      polyposis in adults and maxillary shape. The flattening and shallowing of the
      maxillary arch detected in patients with NP may indicate that the bony structural
      changes continue in adulthood.

PMID- 20039232
TI  - Cystic adventitial disease of the popliteal artery.
AB  - Cystic adventitial disease is a rare condition that usually affects the popliteal
      artery, and is a rare cause of non-atherosclerotic stenosis. It is most commonly
      found in young or middle-aged men with intermittent claudication. Herein we
      present a histologically proven case of cystic adventitial disease of the
      popliteal artery in a 53-year-old man. We describe the imaging findings on gray
      scale, Doppler and triplex ultrasonography, computed tomography with 3D
      reconstruction and digital subtraction angiography.

PMID- 20039233
TI  - Radiologic findings of a traumatic urethral diverticulum with stones in an
      infertile male patient.
AB  - Urethral diverticulum is rarely encountered in male patients. Although
      postmicturition dribble, pain and infection are usually present, infertility is
      rarely reported in urethral diverticulum. We present a case with urethral
      diverticulum associated with infertility, which was diagnosed radiologically.

PMID- 20039234
TI  - Pregnancy after embolization of an ovarian varicocele associated with
      infertility: report of two cases.
AB  - We describe two cases of left-sided ovarian varicocele in patients with
      infertility. Pregnancy occurred in both women after successful retrograde venous
      embolization. Ovarian varicocele may be associated with infertility in some
      patients.

PMID- 20039235
TI  - Final destination of an ingested needle: the liver.
AB  - Foreign body ingestion is a common problem in children, but it is also seen among
      adults. Most foreign bodies pass through the gastrointestinal tract without
      causing complications. Perforation of the gut by a foreign body, followed by
      migration of the foreign body to the liver is quite rare. Herein we report a case
      of inadvertent ingestion of a sewing needle that perforated the duodenum and
      migrated to the liver. The patient was monitored weekly with abdominal
      radiographs, but displacement of the needle could not be observed. At follow-up,
      right upper quadrant pain was noted. Two weeks later, computed tomography
      revealed that the needle was completely buried into the right lobe of the liver.
      Ultrasonographic examination successfully showed the extracapsular displacement
      of the needle. Eventually, laparoscopic removal of the needle was easily
      performed.

PMID- 20039236
TI  - MRI findings of papillary cystadenocarcinoma of the submandibular gland.
AB  - Papillary cystadenocarcinoma is an extremely rare malignant tumor of the salivary
      glands. Major locations of this neoplasm are the parotid gland, sublingual gland,
      and minor salivary glands, while occurrence in the submandibular gland is
      extremely rare. Magnetic resonance imaging (MRI) findings of this lesion have not
      been reported in the literature. Herein, we present a case of papillary
      cystadenocarcinoma arising from the right submandibular gland. MRI showed a 5-cm
      mass composed of solid and cystic components in the mildly enlarged gland.
      Pathologic evaluation revealed papillary cystadenocarcinoma.

PMID- 20039237
TI  - Protein Dimerization Induced by Supramolecular Interactions with Cucurbit[8]uril.

PMID- 20039238
TI  - Regioselective oxidative cleavage of benzylidene acetals: synthesis of alpha- and
      beta-benzoyloxy carboxylic acids.

PMID- 20039239
TI  - Ruthenium bis(sigma-B-H) aminoborane complexes from dehydrogenation of amine
      boranes: trapping of H(2)B-NH(2).

PMID- 20039240
TI  - Highly active mesoporous Nb-W oxide solid-acid catalyst.

PMID- 20039241
TI  - Wacker-type oxidation of internal olefins using a PdCl2/N,N-dimethylacetamide
      catalyst system under copper-free reaction conditions.

PMID- 20039242
TI  - Iron-catalyzed cyclopropanation with trifluoroethylamine hydrochloride and
      olefins in aqueous media: in situ generation of trifluoromethyl diazomethane.

PMID- 20039243
TI  - The canonical helix of urea oligomers at atomic resolution: insights into folding
      induced axial organization.

PMID- 20039244
TI  - Anion-exchange-triggered 1,3-shift of an NH proton to iridium in protic n
      heterocyclic carbenes: hydrogen-bonding and ion-pairing effects.

PMID- 20039245
TI  - Olefin-oxazolines (OlefOx): highly modular, easily tunable ligands for asymmetric
      catalysis.

PMID- 20039247
TI  - Asymmetric alkynylation of imines by cooperative hydrogen bonding and metal
      catalysis.

PMID- 20039246
TI  - Lipophilic pyridinium bisphosphonates: potent gammadelta T cell stimulators.

PMID- 20039248
TI  - Total synthesis and absolute configuration of macrocidin A, a cyclophane tetramic
      acid natural product.

PMID- 20039249
TI  - Controlling molecular rotary motion with a self-complexing lock.

PMID- 20039250
TI  - NDTB-1: a supertetrahedral cationic framework that removes TcO4- from solution.

PMID- 20039251
TI  - Chemically induced cardiomyogenesis of mouse embryonic stem cells.
AB  - A transgenic murine embryonic stem (ES) cell lineage expressing enhanced green
      fluorescent protein (EGFP) under the control of alpha-myosine heavy chain (alpha
      MHC) promoter (palpha-MHC-EGFP) was used to investigate the effects of (thio)urea
      and cinchona alkaloid derivatives on cardiomyogenesis. The screening of the
      compounds yielded cardiomyogenesis inducing substances with good (IV-5, V-4) to
      very good activities (II-16, IV-8), as determined by a 50 to 80 % increase in the
      EGFP fluorescence compared to untreated cells. Time-dependent screening
      approaches in which compounds were added at different developmental stages of the
      ES cells appeared to be of limited suitability for the identification of
      potential cellular targets.

PMID- 20039252
TI  - Uracil-catalyzed synthesis of acetyl phosphate: a photochemical driver for
      protometabolism.
AB  - Progress toward a protometabolism (the earliest energy storage networks) has been
      severely hindered by a shortage of driver reactions, which could have harnessed
      solar photons or coupled electron sources/sinks on the primordial Earth. Here, it
      is reported for the first time that thioacetate can be converted into a known
      metabolite, acetyl phosphate, by ultraviolet light and in aqueous solution at
      neutral pH. Of more compelling importance, the synthesis is catalyzed by uracil,
      which suggests that a genetic component may have also facilitated the emergence
      of metabolic pathways. The chemistry of acetyl phosphate has been extensively
      studied, and it is known to be a precursor of phosphate esters, pyrophosphate and
      possibly longer inorganic chains. Moreover, its bifunctional reactivity (as
      either an acetyl or phosphoryl donor) would have been integral for the first
      metabolic cycles.

PMID- 20039253
TI  - Analysis of the liposidomycin gene cluster leads to the identification of new
      caprazamycin derivatives.

PMID- 20039254
TI  - A beta/gamma motif to mimic alpha-helical turns in proteins.

PMID- 20039255
TI  - Electrochemical deposition of ZnO nanorods on transparent reduced graphene oxide
      electrodes for hybrid solar cells.
AB  - Monocrystalline ZnO nanorods (NRs) with high donor concentration are
      electrochemically deposited on highly conductive reduced graphene oxide (rGO)
      films on quartz. The film thickness, optical transmittance, sheet resistance, and
      roughness of rGO films are systematically studied. The obtained ZnO NRs on rGO
      films are characterized by X-ray diffraction, transmission electron microscopy,
      photoluminescence, and Raman spectra. As a proof-of-concept application, the
      obtained ZnO NRs on rGO are used to fabricate inorganic-organic hybrid solar
      cells with layered structure of quartz/rGO/ZnO NR/poly(3-hexylthiophene)/poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (P3HT/PEDOT:PSS)/Au. The observed
      power conversion efficiency (PCE, eta), approximately 0.31%, is higher than that
      reported in previous solar cells by using graphene films as electrodes. These
      results clearly demonstrate that rGO films with a higher conductivity have a
      smaller work function and show a better performance in the fabricated solar
      cells.

PMID- 20039256
TI  - Associations between sleep quality with cardiorespiratory fitness and BMI among
      adolescent girls.
AB  - The main goal of this study was to examine the association between sleeping
      quality with cardiorespiratory fitness (CRF) and obesity status (BMI) This was a
      cross-sectional study of 1,726 adolescent girls, aged 10 to 18 years. CRF was
      predicted by maximal multistage 20 m shuttle-run test according to procedures
      described from FITNESSGRAM. Children's BMI was classified according to
      International Obesity Task Force and sleeping quality was assessed by
      questionnaire. The prevalence of overweight and obesity was 21.2% and 5.7%,
      respectively. Sleeping quality was significantly associated with CRF (Rho = 0.17;
      P < 0.05), but not with BMI. Girls who were classified as fit were more likely
      (OR: 2.25; P < 0.05) to report better sleep quality compared to their unfit
      peers. Poor sleep quality was associated with lower CRF although no associations
      have been shown with BMI.

PMID- 20039257
TI  - Modeling multisystem biological risk in young adults: The Coronary Artery Risk
      Development in Young Adults Study.
AB  - Although much prior research has focused on identifying the roles of major
      regulatory systems in health risks, the concept of allostatic load (AL) focuses
      on the importance of a more multisystems view of health risks. How best to
      operationalize allostatic load, however, remains the subject of some debate. We
      sought to test a hypothesized metafactor model of allostatic load composed of a
      number of biological system factors, and to investigate model invariance across
      sex and ethnicity. Biological data from 782 men and women, aged 32-47, from the
      Oakland, CA and Chicago, IL sites of the Coronary Artery Risk Development in
      Young Adults Study (CARDIA) were collected as part of the Year 15exam in 2000.
      These include measures of blood pressure, metabolic parameters (glucose, insulin,
      lipid profiles, and waist circumference), markers of inflammation (interleukin-6,
      C-reactive protein, and fibrinogen), heart rate variability, sympathetic nervous
      system activity (12-hr urinary norepinephrine and epinephrine) and hypothalamic
      pituitary-adrenal axis activity (diurnal salivary free cortisol). A "metafactor"
      model of AL as an aggregate measure of six underlying latent biological
      subfactors was found to fit the data, with the metafactor structure capturing 84%
      of variance of all pairwise associations among biological subsystems. There was
      little evidence of model variance across sex and/or ethnicity. These analyses
      extend work operationalizing AL as a multisystems index of biological
      dysregulation, providing initial support for a model of AL as a metaconstruct of
      inter-relationships among multiple biological regulatory systems, that varies
      little across sex or ethnicity.

PMID- 20039258
TI  - MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell
      differentiation.
AB  - Differentiation of mesenchymal stem cells into a particular lineage is tightly
      regulated, and malfunction of this regulation could lead to pathological
      consequences. Patients with osteoporosis have increased adipocyte accumulation,
      but the mechanisms involved remain to be defined. In this study, we aimed to
      investigate if microRNAs regulate mesenchymal progenitor cells and bone marrow
      stromal cell (BMSC) differentiation through modulation of Runx2, a key
      transcription factor for osteogenesis. We found that miR-204 and its homolog miR
      211 were expressed in mesenchymal progenitor cell lines and BMSCs and their
      expression was induced during adipocyte differentiation, whereas Runx2 protein
      expression was suppressed. Retroviral overexpression of miR-204 or transfection
      of miR-204 oligo decreased Runx2 protein levels and miR-204 inhibition
      significantly elevated Runx2 protein levels, suggesting that miR-204 acts as an
      endogenous attenuator of Runx2 in mesenchymal progenitor cells and BMSCs.
      Mutations of putative miR-204 binding sites upregulated the Runx2 3'-UTR reporter
      activity, suggesting that miR-204/211 bind to Runx2 3'-UTR. Perturbation of miR
      204 resulted in altered differentiation fate of mesenchymal progenitor cells and
      BMSCs: osteoblast differentiation was inhibited and adipocyte differentiation was
      promoted when miR-204 was overexpressed in these cells, whereasosteogenesis was
      upregulated and adipocyte formation was impaired when miR-204 was inhibited.
      Together, our data demonstrated that miR-204/211 act as important endogenous
      negative regulators of Runx2, which inhibit osteogenesis and promote adipogenesis
      of mesenchymal progenitor cells and BMSCs.

PMID- 20039264
TI  - Developmental experience alters information coding in auditory midbrain and
      forebrain neurons.
AB  - In songbirds, species identity and developmental experience shape vocal behavior
      and behavioral responses to vocalizations. The interaction of species identity
      and developmental experience may also shape the coding properties of sensory
      neurons. We tested whether responses of auditory midbrain and forebrain neurons
      to songs differed between species and between groups of conspecific birds with
      different developmental exposure to song. We also compared responses of
      individual neurons to conspecific and heterospecific songs. Zebra and Bengalese
      finches that were raised and tutored by conspecific birds, and zebra finches that
      were cross-tutored by Bengalese finches were studied. Single-unit responses to
      zebra and Bengalese finch songs were recorded and analyzed by calculating mutual
      information (MI), response reliability, mean spike rate, fluctuations in time
      varying spike rate, distributions of time-varying spike rates, and neural
      discrimination of individual songs. MI quantifies a response's capacity to encode
      information about a stimulus. In midbrain and forebrain neurons, MI was
      significantly higher in normal zebra finch neurons than in Bengalese finch and
      cross-tutored zebra finch neurons, but not between Bengalese finch and cross
      tutored zebra finch neurons. Information rate differences were largely due to
      spike rate differences. MI did not differ between responses to conspecific and
      heterospecific songs. Therefore, neurons from normal zebra finches encoded more
      information about songs than did neurons from other birds, but conspecific and
      heterospecific songs were encoded equally. Neural discrimination of songs and MI
      were highly correlated. Results demonstrate that developmental exposure to
      vocalizations shapes the information coding properties of songbird auditory
      neurons.

PMID- 20039262
TI  - A novel recessive Nefl mutation causes a severe, early-onset axonal neuropathy.
AB  - OBJECTIVE: To report the first cases of a homozygous recessive mutation in NEFL,
      the gene that encodes the light subunit of neurofilaments. METHODS: Clinical and
      electrophysiologic data were evaluated, and a sural nerve biopsy from one
      affected child was examined by immunohistochemistry and electron microscopy. The
      ability of the mutant protein to form filaments was characterized in an
      established cell culture system. RESULTS: Four of five siblings developed of a
      severe, progressive neuropathy beginning in early childhood. Serial nerve
      conduction studies showed progressively reduced amplitudes with age and
      pronounced slowing at all ages. Visual-evoked responses were slowed in three
      children, indicating that central nervous system axons were subclinically
      involved. All four affected children were homozygous for a nonsense mutation at
      glutamate 210 (E210X) in the NEFL gene; both parents were heterozygous carriers.
      A sural nerve biopsy from an affected patient showed markedly reduced numbers of
      myelinated axons; the remaining myelinated axons were small and lacked
      intermediate filaments. The E210X mutant protein did not form an intermediate
      filament network and did not interfere with the filament formation by wild-type
      human light subunit of neurofilaments in SW-13 vim(-) cells. INTERPRETATION: This
      is the first demonstration of a recessive NEFL mutation, which appears to cause a
      simple loss of function, resulting in a severe, early-onset axonal neuropathy
      with unique features. These results confirm that neurofilaments are the main
      determinant of axonal caliber and conduction velocity, and demonstrate for the
      first time that neurofilaments are required for the maintenance of myelinated
      peripheral nervous system axons.

PMID- 20039265
TI  - Microwave-based alkali pretreatment of switchgrass and coastal bermudagrass for
      bioethanol production.
AB  - Switchgrass and coastal bermudagrass are promising lignocellulosic feedstocks for
      bioethanol production. However, pretreatment of lignocelluloses is required to
      improve production of fermentable sugars from enzymatic hydrolysis. Microwave
      based alkali pretreatment of switchgrass and coastal bermudagrass was
      investigated in this study. Pretreatments were carried out by immersing the
      biomass in dilute alkali reagents and exposing the slurry to microwave radiation
      at 250 W for residence times ranging from 5 to 20 min. Simons' stain method was
      used to quantify changes in biomass porosity as a result of the pretreatment.
      Pretreatments were evaluated based on yields of total reducing sugars, glucose,
      and xylose. An evaluation of different alkalis identified sodium hydroxide as the
      most effective alkali reagent for microwave-based pretreatment of switchgrass and
      coastal bermudagrass. 82% glucose and 63% xylose yields were achieved for
      switchgrass and 87% glucose and 59% xylose yields were achieved for coastal
      bermudagrass following enzymatic hydrolysis of biomass pretreated under optimal
      conditions. Dielectric properties for dilute sodium hydroxide solutions were
      measured and compared with solid losses, lignin reduction, and reducing sugar
      levels in hydrolyzates. Results indicate that dielectric loss tangent of alkali
      solutions is a potential indicator of the severity of microwave-based
      pretreatments.

PMID- 20039266
TI  - Disaggregation of high-molecular weight species during downstream processing to
      recover functional monomer.
AB  - The use of chaotropic agents to recover functional monomeric material was
      investigated for the downstream purification of an Fc-fusion protein containing
      high levels of high-molecular weight (HMW) species. In batch studies, chaotropic
      agents irreversibly disaggregated a majority of the aggregated protein. An
      integrated processing mode, termed as on-column disaggregation, was developed in
      which the protein was captured on Protein A chromatography and then a chaotropic
      agent was used to simultaneously elute the bound protein and disaggregate the HMW
      species. On-column disaggregation process resulted in protein recoveries of >95%
      and aggregation reduction of approximately 50%. Analytical results are presented
      showing that the recovered monomeric material was comparable to the reference
      protein in biochemical, biophysical, and pharmacokinetic properties. The kinetic
      and molecular mechanisms governing protein aggregation and disaggregation will
      also be elucidated. For the Fc-fusion protein studied here, incorporation of the
      disaggregation strategy in both batch and on-column modes led to an increase of
      >10% in overall downstream yield.

PMID- 20039267
TI  - Bone morphogenetic protein 2 and dexamethasone synergistically increase alkaline
      phosphatase levels through JAK/STAT signaling in C3H10T1/2 cells.
AB  - Alkaline phosphatase (ALP) is generally believed to be a faithful marker of
      osteoblast differentiation, and its expression is induced by bone morphogenetic
      protein-2 (BMP-2) and dexamethasone (Dex). However, the effects of combined
      administration of BMP-2 and Dex on ALP transcription have not been extensively
      examined. In this study, we found that BMP-2 and Dex synergistically increase ALP
      levels in mouse C3H10T1/2 pluripotent stem cells. However, switching from one
      inducer to the other, by adding BMP-2 or Dex to cell cultures at different times,
      was no more effective than continuous treatment with either inducer alone. A
      significant induction of ALP mRNA expression was observed only in cells
      continuously treated with both inducers. This result suggests that both BMP-2 and
      Dex may act in the same pathway or at the same stage of differentiation. A
      luciferase assay using ALP promoter deletion constructs showed that a region of
      the promoter containing a putative signal transducer and activator of
      transcription 3 (STAT3) response element (SRE) responds to treatment with a
      combination of BMP-2 and Dex. Furthermore, a ChIP assay indicated that STAT3
      bound to the SRE. In addition, a STAT3 siRNA suppressed the synergistic effect of
      BMP-2 and Dex on ALP levels. These results indicate that STAT3 may play an
      important role in regulating ALP expression. To our knowledge, this is the first
      time that STAT3 has been implicated in the regulation of ALP expression by BMP-2
      and Dex. These findings raise the possibility of developing new strategies for
      the enhancement of bone formation using a combination of BMPs and Dex.

PMID- 20039269
TI  - Multiple Ca2+ signaling pathways regulate intracellular Ca2+ activity in human
      cardiac fibroblasts.
AB  - Ca(2+) signaling pathways are well studied in cardiac myocytes, but not in
      cardiac fibroblasts. The aim of the present study is to characterize Ca(2+)
      signaling pathways in cultured human cardiac fibroblasts using confocal scanning
      microscope and RT-PCR techniques. It was found that spontaneous intracellular
      Ca(2+) (Ca(i) (2+)) oscillations were present in about 29% of human cardiac
      fibroblasts, and the number of cells with Ca(i) (2+) oscillations was increased
      to 57.3% by application of 3% fetal bovine serum. Ca(i) (2+) oscillations were
      dependent on Ca(2+) entry. Ca(i) (2+) oscillations were abolished by the store
      operated Ca(2+) (SOC) entry channel blocker La(3+), the phospholipase C inhibitor
      U-73122, and the inositol trisphosphate receptors (IP3Rs) inhibitor 2
      aminoethoxydiphenyl borate, but not by ryanodine. The IP3R agonist thimerosal
      enhanced Ca(i) (2+) oscillations. Inhibition of plasma membrane Ca(2+) pump
      (PMCA) and Na(+)-Ca(2+) exchanger (NCX) also suppressed Ca(i) (2+) oscillations.
      In addition, the frequency of Ca(i) (2+) oscillations was reduced by nifedipine,
      and increased by Bay K8644 in cells with spontaneous Ca(2+) oscillations. RT-PCR
      revealed that mRNAs for IP3R1-3, SERCA1-3, Ca(V)1.2, NCX3, PMCA1,3,4,
      TRPC1,3,4,6, STIM1, and Orai1-3, were readily detectable, but not RyRs. Our
      results demonstrate for the first time that spontaneous Ca(i) (2+) oscillations
      are present in cultured human cardiac fibroblasts and are regulated by multiple
      Ca(2+) pathways, which are not identical to those of the well-studied contractile
      cardiomyocytes. This study provides a base for future investigations into how
      Ca(2+) signals regulate biological activity in human cardiac fibroblasts and
      cardiac remodeling under pathological conditions.

PMID- 20039268
TI  - Laminin-332-beta1 integrin interactions negatively regulate invadopodia.
AB  - Adhesion of epithelial cells to basement membranes (BM) occurs through two major
      structures: actin-associated focal contacts and keratin-associated
      hemidesmosomes, both of which form on laminin-332 (Ln-332). In epithelial-derived
      cancer cells, additional actin-linked structures with putative adhesive
      properties, invadopodia, are frequently present and mediate BM degradation. A
      recent study proposed that BM invasion requires a proper combination of focal
      contacts and invadopodia for invading cells to gain traction through degraded BM,
      and suggested that these structures may compete for common molecular components
      such as Src kinase. In this study, we tested the role of the Ln-332 in regulating
      invadopodia in 804G rat bladder carcinoma cells, a cell line that secretes Ln-332
      and forms all three types of adhesions. Expression of shRNA to Ln-332 gamma2
      chain (gamma2-kd) led to increased numbers of invadopodia and enhanced
      extracellular matrix degradation. Replating gamma2-kd cells on Ln-332 or collagen
      I fully recovered cell spreading and inhibition of invadopodia. Inhibition of
      alpha3 or beta1, but not alpha6 or beta4, phenocopied the effect of gamma2-kd,
      suggesting that alpha3beta1-mediated focal contacts, rather than alpha6beta4
      mediated hemidesmosome pathways, intersect with invadopodia regulation. gamma2-kd
      cells exhibited alterations in focal contact-type structures and in activation of
      focal adhesion kinase (FAK) and Src kinase. Inhibition of FAK also increased
      invadopodia number, which was reversible with Src inhibition. These data are
      consistent with a model whereby actin-based adhesions can limit the availability
      of active Src that is capable of invadopodia initiation and identifies Ln-332
      beta1 interactions as a potent upstream regulator that limits cell invasion.

PMID- 20039270
TI  - Downregulation and aberrant promoter methylation of p16INK4A: a possible novel
      heritable susceptibility marker to retinoblastoma.
AB  - RB loss has long been recognized as the causative genetic alteration underlying
      retinoblastoma but it is increasingly evident that other alterations are required
      for the tumor to develop. Therefore, we set out to identify additional
      inheritable susceptibility markers and new potential preventive and therapeutic
      targets for retinoblastoma. We focused on the p16INK4A tumor suppressor gene
      because of its possible role in retinoblastoma pathogenesis and its involvement
      in predisposition to familial cancer. p16INK4A expression was analyzed in tumor
      samples from retinoblastoma patients by immunohistochemistry and in peripheral
      blood cells from both patients and their parents by real-time quantitative
      reverse transcription-PCR (qRT-PCR). Since promoter methylation is a common
      mechanism regulating p16INK4A expression, the methylation status of its promoter
      was also analyzed in blood samples from patients and their parents by methylation
      specific PCR. A downregulation of p16INK4A was observed in 55% of retinoblastoma
      patients. Interestingly, in 56% of the cases showing p16INK4A downregulation at
      least one of the patients' parents bore the same alteration in blood cells.
      Analysis of p16INK4A promoter methylation showed hypermethylation in most
      patients with p16INK4A downregulation and in the parents with the same alteration
      in p16INK4A expression. The finding that p16INK4A was downregulated both in
      patients and their parents suggests that this alteration could be a novel
      inheritable susceptibility marker to retinoblastoma. The observation that
      p16INK4A downregulation seems to be due to its promoter hypermethylation opens
      the way for the development of new preventive and therapeutic strategies using
      demethylating agents.

PMID- 20039271
TI  - Heat shock but not cold shock leads to disturbed intracellular zinc homeostasis.
AB  - The heat shock response is a highly conserved process essential for surviving
      environmental stress, including extremes of temperature. To investigate whether
      heat shock has an impact on intracellular Zn(2+) homeostasis, cells were
      subjected to heat shock, and subsequently the intracellular free zinc
      concentration was investigated. Sublethal heat shock induced a temperature
      dependent and transient intracellular Zn(2+) release that was repeatable after 24
      h. The free zinc was localized in round-shaped nuclear bodies identified as
      nucleoli. Metallothionein, the main cellular zinc storing protein, was found to
      be not functionally essential for this heat-shock-induced effect. No significant
      oxidative stress within the cells was detected after heat shock. Cold shock and
      subsequent rewarming did not result in disturbed intracellular zinc homeostasis.
      These results show that heat shock and cold shock differ with respect to
      intracellular Zn(2+) release. A role for zinc as signaling ion during fever is
      conceivable.

PMID- 20039272
TI  - Metalloproteinases and their regulators in colorectal cancer.
AB  - Metalloproteinases (MPs) such as the matrix metalloproteinases (MMPs) and
      adamalysins (ADAMs and ADAMTS) are expressed in various stages of colorectal
      cancer (CRC), and some correlate with survival and prognosis. The MPs are
      regulated by various factors including EMMPRIN, TIMPs, and RECK. In addition,
      micro-RNAs are found to be relevant for both MP expression levels and CRC
      prognostication. Both MPs and their regulators could be potential targets for
      intervention and therapy in CRC.

PMID- 20039273
TI  - Single-cell analysis of p16(INK4a) and p21(WAF1) expression suggests distinct
      mechanisms of senescence in normal human and Li-Fraumeni Syndrome fibroblasts.
AB  - Herein we used single-cell observation methods to gain insight into the roles of
      p16(INK4A) and p21(WAF1) (hereafter p16 and p21) in replicative senescence and
      ionizing radiation-induced accelerated senescence in human [normal, ataxia
      telangiectasia (AT) and Li-Fraumeni syndrome (LFS)] fibroblast strains. Cultures
      of all strains entered a state of replicative senescence at late passages, as
      evident from inhibition of growth, acquisition of flattened and enlarged cell
      morphology, and positive staining for senescence-associated beta-galactosidase.
      In addition, proliferating early-passage cultures of these strains exhibited
      accelerated senescence in response to ionizing radiation. Immunofluorescence
      microscopy revealed the heterogeneous expression of p16 in normal and AT
      fibroblast strains, with the majority of the cells exhibiting undetectable levels
      of p16 irrespective of in vitro culture age. Importantly, replicative senescence
      as well as accelerated senescence triggered by ionizing radiation were
      accompanied by sustained nuclear accumulation of p21, but did not correlate with
      p16 expression in p53-proficient (normal and AT) fibroblasts. In p53-deficient
      (LFS) fibroblasts, on the other hand, replicative senescence and ionizing
      radiation-triggered accelerated senescence strongly correlated with expression of
      p16 but not of p21. Furthermore, senescence in LFS fibroblasts was associated
      with genomic instability encompassing polyploidy. Our findings are compatible
      with a model in which p16 serves as a backup regulator of senescence, triggering
      this response preferentially in the absence of wild-type p53 activity. The
      possibility that one of the tumor-suppressor functions of p16 may be associated
      with genomic instability, preventing the emergence of malignant progeny from
      polyploid giant cells, is also supported by these results.

PMID- 20039276
TI  - Gastric cancer patients with COPD: laparoscopic or open gastrectomy?

PMID- 20039275
TI  - T-cadherin modulates endothelial barrier function.
AB  - T-cadherin is an atypical member of the cadherin family, which lacks the
      transmembrane and intracellular domains and is attached to the plasma membrane
      via a glycosylphosphatidylinositol anchor. Unlike canonical cadherins, it is
      believed to function primarily as a signaling molecule. T-cadherin is highly
      expressed in endothelium. Using transendothelial electrical resistance
      measurements and siRNA-mediated depletion of T-cadherin in human umbilical vein
      endothelial cells, we examined its involvement in regulation of endothelial
      barrier. We found that in resting confluent monolayers adjusted either to 1% or
      10% serum, T-cadherin depletion modestly, but consistently reduced
      transendothelial resistance. This was accompanied by increased phosphorylation of
      Akt and LIM kinase, reduced phosphorylation of p38 MAP kinase, but no difference
      in tubulin acetylation and in phosphorylation of an actin filament severing
      protein cofilin and myosin light chain kinase. Serum stimulation elicited a
      biphasic increase in resistance with peaks at 0.5 and 4-5 h, which was suppressed
      by a PI3 kinase/Akt inhibitor wortmannin and a p38 inhibitor SB 239063. T
      cadherin depletion increased transendothelial resistance between the two peaks
      and reduced the amplitude of the second peak. T-cadherin depletion abrogated
      serum-induced Akt phosphorylation at Thr308 and reduced phosphorylation at
      Ser473, reduced phosphorylation of cofilin, and accelerated tubulin
      deacetylation. Adiponectin slightly improved transendothelial resistance
      irrespectively of T-cadherin depletion. T-cadherin depletion also resulted in a
      reduced sensitivity and delayed responses to thrombin. These data implicate T
      cadherin in regulation of endothelial barrier function, and suggest a complex
      signaling network that links T-cadherin and regulation of barrier function.

PMID- 20039274
TI  - RANKL induces heterogeneous DC-STAMP(lo) and DC-STAMP(hi) osteoclast precursors
      of which the DC-STAMP(lo) precursors are the master fusogens.
AB  - Osteoclasts (OC) are multinucleated bone resorbing cells that form via RANKL
      induced fusion of heterogeneous mononuclear OC precursors (OCP). Currently, there
      are no unique surface markers to distinguish these OCP populations, which are
      diagnostic for erosive and metabolic bone diseases using culture assays. Thus, we
      investigated expression of DC-STAMP, a surface receptor required for OCP fusion,
      during osteoclastogenesis in vitro using a novel monoclonal antibody (1A2).
      Immunoprecipitation-Western blot analysis of OCP membrane proteins detected 106
      kDa dimeric and 53 kDa monomeric DC-STAMP in non-denaturing and denaturing
      conditions, respectively, with greater sensitivity versus rabbit anti-sera
      (KR104). 1A2 also detected 99.9% of undifferentiated monocytes as a single
      population by flow cytometry with a MFI 100-fold over background, while KR104 was
      not useful in this assay. Functionally, 1A2 inhibited OCP fusion in vitro. RANKL
      stimulation of OCP induced DC-STAMP(lo) and DC-STAMP(hi) cells, which mature into
      OC and mononuclear cells respectively as determined by fluorescent microscopy and
      TRAP assays. Addition of DC-STAMP(hi) cells to purified DC-STAMP(lo) cultures
      produced larger, more nucleated OC vs. pure DC-STAMP(lo) cultures. RT-qPCR
      analysis of these two populations showed that OC markers (Trap and Oc-stamp) and
      fusogenic gene expression (Cd9 and Cd47), were significantly increased in DC
      STAMP(lo) vs. DC-STAMP(hi) cells. Collectively, these results demonstrate that DC
      STAMP is expressed on OCP as a dimer, which is efficiently detected by 1A2 via
      flow cytometry. RANKL induces osteoclastogenesis by stimulating DC-STAMP
      internalization in some OCP, and these DC-STAMP(lo) cells display the "master
      fusogen" phenotype. In contrast, DC-STAMP(hi) OCP can only act as mononuclear
      donors.

PMID- 20039277
TI  - Surgical management for a malignant bowel obstruction with recurrent
      gastrointestinal carcinoma.
AB  - BACKGROUND: A malignant bowel obstruction (MBO) is a common clinical complication
      in patients with recurrent gastrointestinal carcinoma, which has a poor prognosis
      and a limited life expectancy. This study considered the effectiveness of
      surgical management for MBO. METHODS: This study reviewed the clinical course of
      70 patients who underwent surgery for MBO and compared the outcomes in three
      groups: patients with (A) peritonitis carcinomatosis without manifest ascites,
      (B) peritonitis carcinomatosis with ascites, (C) local recurrence without
      peritonitis carcinomatosis. RESULTS: The 1-year survival rate and median survival
      time (MST) in the patients in group A were 33.3% and 228 days, which was
      statistically longer than those (6.7% and 46 days) in the patients in group B (P
      = 0.026). The rate of the patients with possible oral intake of solid meals for 6
      months and median oral intake periods were 45.4% and 161 days in patients in
      group A and 28.0% and 93 days in patients in group C. In contrast, 66.7% in group
      B could not take solid meals for more than 1 month, and five patients could not
      take solid meals at all. CONCLUSION: Palliative operations for the patients with
      manifest ascites of MBO are risky and rarely effectively improve oral intake, but
      this is not considered to be a contraindication for surgical management. Informed
      consent is therefore important in the surgical management of MBO.

PMID- 20039278
TI  - SCRN1 is a novel marker for prognosis in colorectal cancer.
AB  - PURPOSE: Secernin 1 (SCRN1) is a member of the secernin family and is reported to
      be a tumor-associated antigen. Previous reports show that SCRN1 is upregulated in
      gastric cancer cell lines and may be a novel immunotherapy target, whereas its
      significance in colorectal cancer (CRC) is not fully understood. MATERIALS AND
      METHODS: The present study comprised 54 patients who underwent surgery for CRC,
      as well as two cell lines derived from human CRC. We assessed the correlation of
      gene expression with clinical parameters in the CRC patients, and knockdown was
      evaluated in the cell lines. RESULTS: Thirty of the 54 (55.5%) cases exhibited a
      higher expression of the SCRN1 gene in cancerous regions than marginal non
      cancerous regions. Patients with high SCRN1 expression were statistically
      susceptible to a poor prognosis and showed poorer disease-free survival than
      those with low expression. SCRN1 knockdown in the two cell lines demonstrated
      that the siRNA inhibition resulted in a statistically significant reduction in
      cell growth. CONCLUSION: The present data strongly suggest that SCRN1 expression
      is a prognostic factor in CRC patients.

PMID- 20039279
TI  - Identification of microRNAs controlling human ovarian cell proliferation and
      apoptosis.
AB  - Previous studies have shown that microRNAs (miRNAs) can control steroidogenesis
      in cultured granulosa cells. In this study we wanted to determine if miRNAs can
      also affect proliferation and apoptosis in human ovarian cells. The effect of
      transfection of cultured primary ovarian granulosa cells with 80 different
      constructs encoding human pre-miRNAs on the expression of the proliferation
      marker, PCNA, and the apoptosis marker, Bax was evaluated by immunocytochemistry.
      Eleven out of 80 tested miRNA constructs resulted in stimulation, and 53 miRNAs
      inhibited expression of PCNA. Furthermore, 11 of the 80 miRNAs tested promoted
      accumulation of Bax, while 46 miRNAs caused a reduction in Bax in human ovarian
      cells. In addition, two selected antisense constructs that block the
      corresponding miRNAs mir-15a and mir-188 were evaluated for their effects on
      expression of PCNA. An antisense construct inhibiting mir-15a (which precursor
      suppressed PCNA) increased PCNA, whereas an antisense construct for mir-188
      (which precursor did not change PCNA) did not affect PCNA expression.
      Verification of effects of selected pre-mir-10a, mir-105, and mir-182 by using
      other markers of proliferation (cyclin B1) and apoptosis (TdT and caspase 3)
      confirmed specificity of miRNAs effects on these processes. This is the first
      direct demonstration of the involvement of miRNAs in controlling both
      proliferation and apoptosis by ovarian granulose cells, as well as the
      identification of miRNAs promoting and suppressing these processes utilizing a
      genome-wide miRNA screen.

PMID- 20039280
TI  - Prostate stem cell antigen mRNA in peripheral blood as a potential predictor of
      biochemical recurrence in high-risk prostate cancer.
AB  - OBJECTIVE: To determine whether the presence of prostate stem cell antigen (PSCA)
      mRNA in peripheral blood can predict biochemical recurrence (BCR) after radical
      prostatectomy in patients with high-risk prostate cancer. METHODS: High-risk
      disease was defined based on the presence of any one of the following three risk
      factors: prostate-specific antigen (PSA) > or = 20 ng/ml, a biopsy Gleason score
      (GS) > or = 8, or clinical stage > or = T2c. Nested reverse transcriptase
      polymerase chain reaction (RT-PCR) was employed to detect PSCA mRNA-bearing cells
      in peripheral blood. The relationship between PSCA detection and BCR after
      surgery was evaluated. RESULTS: Of the 250 patients, 103 (36.8%) with high-risk
      disease were included in the analysis. PSCA-mRNA was detected in 17 (16.5%) of
      these patients. Patients with high GS (> or = 7) tended to be PSCA-mRNA positive
      status (P = 0.045). Over a median 23 months of follow-up (range 3-47 months), BCR
      developed in 27 patients (26.2%). Cox regression hazards model analysis revealed
      that a RT-PCR PSCA positivity (HR, 4.549; 95%CI, 1.685-12.279; P = 0.003)
      independently increased the risk of BCR. CONCLUSIONS: The presence of PSCA mRNA
      in peripheral blood is a significant predictor of BCR after radical prostatectomy
      in high-risk prostate cancer.

PMID- 20039281
TI  - Validation of a scoring system to predict non-sentinel lymph node metastasis in
      melanoma.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has been widely accepted as the
      lymph node sampling procedure of choice for melanoma patients. Current standards
      of practice suggest completion lymph node dissection (CLND) for patients with a
      positive SLNB result. The rationale for SLNB+/-CLND is for staging and prognosis
      as well as local control and possibly survival improvement. CLND, however,
      entails significant morbidity. In addition, most patients (approximately 80%)
      will have no further melanoma metastases in non-sentinel nodes and these patients
      may not benefit from the additional dissection. We had previously developed a
      score (based on patient age and the total size of metastasis within the SLN) that
      predicted which SLN-positive patients would have a positive CLND. Utilization of
      this scoring system would spare a significant number of melanoma patients the
      risks associated with CLND. The purpose of this study was to validate this score
      using different melanoma populations. METHODS: A retrospective chart review of
      all patients that had undergone SLNB for melanoma at four different Canadian
      centers was undertaken. Data from the Calgary Foothills Medical Center, the
      Winnipeg Health Sciences Center, and the Toronto Sunnybrook Health Sciences
      Center from January 1999 to present was collected. In addition, we identified all
      patients from April 2007 to present at the Misericordia Hospital in Edmonton for
      this study. This patient information had not been utilized when we were
      developing this score. The collected variables included patient age, Breslow
      thickness, result of SLNB, total size of SLN metastasis, largest size of SLN
      metastasis, and results of CLND. Logistic regression was used to test the
      significance of a score system's correlation (based on cutoff age of 55 years and
      cutoff total SLN metastasis of 5 mm) with the CLND results. We also used logistic
      regression to test the correlation of cutoff values of total SLN metastasis with
      non-sentinel lymph node (NSLN) metastasis. RESULTS: Data were collected on 599
      patients across the four centers. Breslow thickness significantly correlated with
      SLN metastasis. The risk score system (based on patient age and total SLN
      metastasis) was significantly predictive of the CLND result in SLNB-positive
      patients. However, the age became non-significant on multivariate analysis. Total
      SLN metastasis emerged as the variable that is most predictive of NSLN
      metastasis. Patients with total SLN metastasis less than 2 mm had a 3.6% risk of
      NSLN metastasis, those with SLN metastasis from 2-5 mm had a 12.5% risk of NSLN
      metastasis, whereas those with total SLN metastasis of 5 mm or greater had a 30%
      risk of NSLN metastasis. CONCLUSION: Using cutoff values of 2 and 5 mm for total
      SLN metastasis, prediction of NSLN metastasis can be made in melanoma patients.
      Patients with less than 2 mm of total SLN metastasis are unlikely (<3.67%
      likelihood) to harbor NSLN metastasis; these patients may not benefit from
      additional nodal dissection beyond SLNB.

PMID- 20039286
TI  - Use of CE for the determination of binding constants.
AB  - In the past two decades, CE has been used frequently for the measurement of
      apparent binding/association constants. CE has numerous advantages, including
      short analysis times, low sample consumption, simplicity of operation, etc. This
      review provides a fundamental introduction to binding theory and then summarizes
      recent applications and advances in the field of CE-based methods for the
      evaluation of molecular association. The time period for this survey is from 2002
      (when our previous review was published) to the present.

PMID- 20039288
TI  - Electrophoretic and electrochromatographic separation of proteins in capillaries:
      an update covering 2007-2009.
AB  - This review article covers 3-year period from 2007 to 2009 and is a continuation
      of the review article by V. Dolnik, [Electrophoresis 2008, 29, 143-156]. This
      article with 125 references describes recent developments in CE and CEC of
      proteins in capillary format and does not cover the developments of CE and CEC in
      microchip format, since Tran et al. review the microchip subject in this special
      issue. The present review article has four major topics including (i) the
      separation media, (ii) multidimensional separations, (iii) detection, and (iv)
      applications.

PMID- 20039289
TI  - Recent developments in PDMS surface modification for microfluidic devices.
AB  - PDMS is enjoying continued and ever increasing popularity as the material of
      choice for microfluidic devices due to its low cost, ease of fabrication, oxygen
      permeability and optical transparency. However, PDMS's hydrophobicity and fast
      hydrophobic recovery after surface hydrophilization, attributed to its low glass
      transition temperature of less than -120 degrees C, negatively impacts on the
      performance of PDMS-based microfluidic device components. This issue has spawned
      a flurry of research to devise longer lasting surface modifications of PDMS, with
      particular emphasis on microfluidic applications. This review will present recent
      research on surface modifications of PDMS using techniques ranging from metal
      layer coatings and layer-by-layer depositions to dynamic surfactant treatments
      and the adsorption of amphipathic proteins. We will also discuss significant
      advances that have been made with a broad palette of gas-phase processing methods
      including plasma processing, sol-gel coatings and chemical vapor deposition.
      Finally, we will present examples of applications and future prospects of
      modified PDMS surfaces in microfluidics, in areas such as molecular separations,
      cell culture in microchannels and biomolecular detection via immunoassays.

PMID- 20039291
TI  - CEC of phytochemical bioactive compounds.
AB  - Although there are many publications related to technological or methodological
      developments of CEC, few focus on the analysis of natural products, especially
      phytochemical bioactive compounds. This review summarized the application of CEC
      in the analysis of phytochemical bioactive components, including flavonoids,
      nucleosides, steroids, lignans, quinones and coumarins, as well as fingerprint
      analysis of herbs. The strategies for optimization of CEC conditions and
      detection were also discussed.

PMID- 20039292
TI  - Recent approaches for enhancing sensitivity in enantioseparations by CE.
AB  - This article reviews the latest methodological and instrumental improvements for
      enhancing sensitivity in chiral analysis by CE. The review covers literature from
      March 2007 until May 2009, that is, the works published after the appearance of
      the latest review article on the same topic by Sanchez-Hernandez et al.
      [Electrophoresis 2008, 29, 237-251]. Off-line and on-line sample treatment
      techniques, on-line sample preconcentration strategies based on electrophoretic
      and chromatographic principles, and alternative detection systems to the widely
      employed UV/Vis detection in CE are the most relevant approaches discussed for
      improving sensitivity. Microchip technologies are also included since they can
      open up great possibilities to achieve sensitive and fast enantiomeric
      separations.

PMID- 20039293
TI  - Capillary and microchip electrophoresis in microdialysis: recent applications.
AB  - The theme of this review is to highlight the importance of microscale
      electrophoretic-based separation systems in microdialysis (microD). The ability
      of CE and MCE to yield very rapid and highly efficient separations using just
      nanolitre volumes of microdialysate samples will also be discussed. Recent
      advances in this area will be highlighted, by illustration of some exciting new
      applications while the need for further innovation will be covered. The first
      section briefly introduces the concept of microD sampling coupled with
      electrophoresis-based separation and the inherent advantages of this approach.
      The following section highlights some specific applications of CE separations in
      the detection of important biomarkers such as low-molecular-weight
      neurotransmitters, amino acids, and other molecules that are frequently
      encountered in microD. Various detection modes in CE are outlined and some of the
      advantages and drawbacks thereof are discussed. The last section introduces the
      concepts of micro-total analysis systems and the coupling of MCE and microD. Some
      of the latest innovations will be illustrated. The concluding section reflects on
      the future of this important chemical alliance between microD and CE/MCE.

PMID- 20039294
TI  - Growing trend of CE at the omics level: the frontier of systems biology.
AB  - In a novel attempt to comprehend the complexity of life, systems biology has
      recently emerged as a state-of-the-art approach for biological research in
      contrast to the reductionist approaches that have been used in molecular cell
      biology since the 1950s. Because a massive amount of information is required in
      many systems biology studies of life processes, we have increasingly come to
      depend on techniques that provide high-throughput omics data. CE and CE coupled
      to MS have served as powerful analytical tools for providing qualitative and
      quantitative omics data. Recent systems biology studies have focused strongly on
      the diagnosis and treatment of diseases. The increasing number of clinical
      research papers on drug discovery and disease therapies reflects this growing
      interest among scientists. Since such clinical research reflects one of the
      ultimate purposes of bioscience, these trends will be sustained for a long time.
      Thus, this review mainly focuses on the application of CE and CE-MS in diagnosis
      as well as on the latest CE methods developed. Furthermore, we outline the new
      challenges that arose in 2008 and later in elucidating the system-level functions
      of the bioconstituents of living organisms.

PMID- 20039295
TI  - iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and
      transcriptional NF-kappaB-dependent blockade.
AB  - In recent years, it has become apparent that the removal of apoptotic cells by
      macrophages and DC is not only noninflammatory, but also immune-inhibitory, in
      most although not all circumstances. Complement may be involved in the uptake of
      apoptotic cells via direct binding of bridging factors in some physiological
      circumstances, by opsonization and engagement of the complement receptors. In the
      current study, we use a complement-dependent system of apoptotic cell clearance
      by human-derived macrophages and DC. Using a luciferase reporter gene and
      measuring immune response to non-opsonic zymosan, we show that iC3b-apoptotic
      cells induce NF-kappaB inhibition in response to zymosan and LPS at the nuclear
      translocation, transcriptional and post-transcriptional levels, leading to
      profound inhibition of proinflammatory cytokines. In addition, interaction with
      iC3b-opsonized apoptotic cells is characterized by macrophage secretion of IL-10
      and lack of TGF-beta secretion. In conclusion, in cells with iC3b receptors,
      opsonized apoptotic cells mediate a distinct anti-inflammatory response and
      transcriptional NF-kappaB-dependent blockage.

PMID- 20039296
TI  - Functional analysis of the CD300e receptor in human monocytes and myeloid
      dendritic cells.
AB  - The CD300e surface molecule, originally termed immune receptor expressed by
      myeloid cells (IREM)-2, was reported to associate with the DNAX-activating
      protein (DAP) 12 adaptor in co-transfected cells, and is capable of signaling. In
      the present report, we investigated in detail the function of CD300e in monocytes
      and myeloid DC (mDC) freshly isolated from peripheral blood of normal blood
      donors. Upon engagement by an agonistic mAb, CD300e triggered an intracellular
      calcium mobilization and superoxide anion O(2) (-) production in monocytes.
      Activation via CD300e provided survival signals that prevented monocyte and mDC
      apoptosis, triggered the production of pro-inflammatory cytokines and upregulated
      the expression of cell surface co-stimulatory molecules in both cell types.
      Moreover, CD300e activation of mDC enhanced the alloreactive response of naive T
      cells. Overall, our data formally support the notion that CD300e functions as an
      activating receptor capable of regulating the innate immune response in myeloid
      cells.

PMID- 20039297
TI  - In vivo depletion of CD4+FOXP3+ Treg cells by the PC61 anti-CD25 monoclonal
      antibody is mediated by FcgammaRIII+ phagocytes.
AB  - Depletion of CD4(+)CD25(+)FoxP3(+) Treg using PC61 mAb (anti-murine CD25 rat
      IgG1) is widely used to characterize Treg function in vivo. However, the
      mechanism of Treg depletion remains largely unknown. Herein, we report the PC61
      mAb's mechanism of action. In peripheral blood, a single injection of PC61 mAb
      eliminated approximately 70% of CD4(+)FoxP3(+) cells with the remaining Treg
      expressing low or no CD25. Functional blockade of Fcgamma receptors with 2.4G2
      mAb significantly inhibited PC61 mAb activity. Furthermore, Fcgamma receptor
      (FcgammaR)III(-/-) mice were resistant to Treg depletion. FcgammaRIII is
      expressed on immune cells including NK cells and macrophages that are the major
      effector cells for Ab-dependent-cellular-cytotoxicity and Ab-dependent-cellular
      phagocytosis, respectively. Depletion of NK cells had no effect, whereas
      depletion of phagocytes, including macrophages, by clodronate liposome
      significantly inhibited Treg depletion. Furthermore, in vitro, PC61 mAb can
      mediate Ab-dependent-cellular-phagocytosis of CD25(+) cells by WT or FcgammaRIIB(
      /-), but not FcgammaRIII(-/-), macrophages. Altogether these data demonstrate the
      critical role of FcgammaRIII(+) phagocytes in mediating Treg depletion by PC61
      mAb. This finding may be useful in guiding the development of human Treg
      targeting therapy.

PMID- 20039298
TI  - The effect of placental malaria infection on cord blood and maternal
      immunoregulatory responses at birth.
AB  - Placental malaria (PM), a frequent infection of pregnancy, provides an ideal
      opportunity to investigate the impact on immune development of exposure of the
      foetal immune system to foreign Ag. We investigated the effect of PM on the
      regulatory phenotype and function of cord blood cells from healthy Gambian
      newborns and peripheral blood cells from their mothers, and analyzed for effects
      on the balance between regulatory and effector responses. Using the gold standard
      for classifying PM we further distinguished between resolved infection and acute
      or chronic PM active at the time of delivery. We show that exposure to malarial
      Ag in utero results in the expansion of malaria-specific FOXP3(+) Treg and more
      generalized FOXP3(+) CD4(+) Treg in chronic and resolved PM, alongside increased
      Th1 pro-inflammatory responses (IFN-gamma, TNF-alpha, IFN-gamma:IL-10) in
      resolved PM infection only. These observations demonstrate a clear effect of
      exposure to malarial Ag in foetal life on the immune environment at birth, with a
      regulatory response dominating in the newborns with ongoing chronic PM, while
      those with resolved infection produce both regulatory and inflammatory responses.
      The findings might explain some of the adverse effects on the health of babies
      born to women with PM.

PMID- 20039299
TI  - Critical role of lipid rafts in CD154-mediated T cell signaling.
AB  - Although signal pathways triggered via the CD40 molecule are well characterized,
      those induced via CD154 are less known. This study demonstrates that engagement
      of CD154 in Jurkat D1.1 cells with soluble CD40 leads to PKC alpha and delta
      activation, calcium mobilization, and phosphorylation of the Map kinases ERK1/2
      and p38. Such response is accompanied by significant recruitment of CD154 into
      lipid rafts. Disruption of lipid rafts integrity with nystatin or methyl beta
      cyclodextrin abrogated PKCalpha PKCdelta and p38 phosphorylation, but had no
      effect on ERK1/2 phosphorylation. Inhibition of PKC activation completely
      abolished p38 phosphorylation but had no effect on ERK1/2 phosphorylation,
      suggesting that localization of CD154 within lipid rafts is an absolute
      requirement for CD154-induced PKCalpha- and PKCdelta-dependent p38
      phosphorylation. Furthermore, CD154 acts as co-stimulator for the production of
      IL-2 in an APC-superantigen-T-cell activation model. The results obtained
      demonstrate for the first time, that lipid rafts are of immunological relevance
      for CD154-triggered signals, and reinforce the importance of CD154 in T-cell
      activation.

PMID- 20039300
TI  - In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade:
      maintained tolerance to normal cells even in the presence of IL-2.
AB  - Missing-self-reactivity can be mimicked by blocking self-specific inhibitory
      receptors on NK cells, leading to increased rejection of syngeneic tumor cells.
      Using a mouse model, we investigated whether Ab-mediated blocking of inhibitory
      receptors, to a degree where NK cells rejected syngeneic tumor cells, would still
      allow self-tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors
      on C57BL/6 (H-2(b)) NK cells were blocked with F(ab')(2) fragments of the mAb
      5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated
      fluorescence-labeled syngeneic lymphoma line cells but not of syngeneic spleen
      cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK
      cell-dependent and specifically induced by Ly49C/I blockade. Moreover, selective
      tumor rejection was maintained after treatment with 5E6 F(ab')(2) for 9 wk,
      arguing against the induction of NK cell anergy or autoreactivity during this
      time. Combination therapy using 5E6 F(ab')(2) together with high dose IL-2
      treatment further increased lymphoma cell rejection. In addition, combination
      therapy reduced growth of melanoma cell line tumors established by s.c.
      inoculation 3 days before start of treatment. Our results demonstrate that
      inhibitory receptor blockade does not result in attack on normal cells, despite
      potent reactivity against MHC class I-expressing tumors.

PMID- 20039301
TI  - DNA vaccination with T-cell epitopes encoded within Ab molecules induces high
      avidity anti-tumor CD8+ T cells.
AB  - Stimulation of high-avidity CTL responses is essential for effective anti-tumor
      and anti-viral vaccines. In this study we have demonstrated that a DNA vaccine
      incorporating CTL epitopes within an Ab molecule results in high-avidity T-cell
      responses to both foreign and self epitopes. The avidity and frequency was
      superior to peptide, peptide-pulsed DC vaccines or a DNA vaccine incorporating
      the epitope within the native Ag. The DNA Ab vaccine was superior to an identical
      protein vaccine that can only cross-present, indicating a role for direct
      presentation by the DNA vaccine. However, the avidity of CTL responses was
      significantly reduced in Fc receptor gamma knockout mice or if the Fc region was
      removed suggesting that cross presentation of Ag via Fc receptor was also
      important in the induction of high-avidity CTL. These results suggest that
      generation of high-avidity CTL responses by the DNA vaccine is related to its
      ability to both directly present and cross-present the epitope. High-avidity
      responses were capable of efficient anti-tumor activity in vitro and in vivo.
      This study demonstrates a vaccine strategy to generate high-avidity CTL responses
      that can be used in anti-tumor and anti-viral vaccine settings.

PMID- 20039303
TI  - Differential regulation of iron homeostasis during human macrophage polarized
      activation.
AB  - Iron metabolism in inflammation has been mostly characterized in macrophages
      exposed to pathogens or inflammatory conditions, mimicked by the combined action
      of LPS and IFN-gamma (M1 polarization). However, macrophages can undergo an
      alternative type of activation stimulated by Th2 cytokines, and acquire a role in
      cell growth and tissue repair control (M2 polarization). We characterized the
      expression of genes related to iron homeostasis in fully differentiated
      unpolarized (M0), M1 and M2 human macrophages. The molecular signature of the M1
      macrophages showed changes in gene expression (ferroportin repression and H
      ferritin induction) that favour iron sequestration in the reticuloendothelial
      system, a hallmark of inflammatory disorders, whereas the M2 macrophages had an
      expression profile (ferroportin upregulation and the downregulation of H ferritin
      and heme oxygenase) that enhanced iron release. The conditioned media from M2
      macrophages promoted cell proliferation more efficiently than those of M1 cells
      and the effect was blunted by iron chelation. The role of ferroportin-mediated
      iron release was demonstrated by the absence of differences from the media of
      macrophages of a patient with loss of function ferroportin mutation. The distinct
      regulation of iron homeostasis in M2 macrophages provides insights into their
      role under pathophysiological conditions.

PMID- 20039302
TI  - S1P3 confers differential S1P-induced migration by autoreactive and non
      autoreactive immature B cells and is required for normal B-cell development.
AB  - During B-cell development, immature B-cell fate is determined by whether the BCR
      is engaged in the bone marrow. Immature B cells that are non-autoreactive
      continue maturation and emigrate from the marrow, whereas autoreactive immature B
      cells remain and are tolerized. However, the microenvironment where these events
      occur and the chemoattractants responsible for immature B-cell trafficking within
      and out of the bone marrow remain largely undefined. Sphingosine 1-phosphate
      (S1P) is a chemoattractant that directs lymphocyte trafficking and thymocyte
      egress and in this study we investigated whether S1P contributes to B-cell
      development, egress and positioning within the bone marrow. Our findings show
      that immature B cells are chemotactic toward S1P but that this response is
      dependent on Ag receptor specificity: non-autoreactive, but not autoreactive,
      immature B cells migrate toward S1P and are shown to require S1P3 receptor for
      this response. Despite this response, S1P3 is shown not to facilitate immature B
      cell egress but is required for normal B-cell development including the
      positioning of transitional B cells within bone marrow sinusoids. These data
      indicate that S1P3 signaling directs immature B cells to a bone marrow
      microenvironment important for both tolerance induction and maturation.

PMID- 20039305
TI  - CD14-independent responses induced by a synthetic lipid A mimetic.
AB  - CRX-527 belongs to a new family of synthetic lipid A mimetics, the aminoalkyl
      glucosaminide 4-phosphates, which are considered as potential vaccine adjuvants
      or stand-alone immunotherapeutics to harness innate immune defenses. Since
      natural lipid A from bacterial LPS depends on membrane-bound (mCD14) or soluble
      CD14 for its TLR4 ligand activity, we investigated the involvement of both forms
      of CD14 in the responses elicited by CRX-527. First, we found that CRX-527
      induces NF-kappaB and interferon regulatory factor-3 (IRF-3) activation in human
      embryonic kidney cells transfected with TLR4 and MD-2 genes alone, whereas the
      responses to LPS require either co-transfection of the gene encoding mCD14 or
      addition of soluble CD14. We then observed that monocyte-derived DC, which are
      devoid of mCD14 respond to CRX-527 but not to LPS in serum-free medium.
      Furthermore, we found that, in contrast to LPS, CRX-527 induces the production of
      cytokines in whole blood of a patient with paroxysmal nocturnal hemoglobinuria, a
      disease in which mCD14-dependent responses are defective. Finally, we
      demonstrated that splenocytes from CD14-deficient mice produce cytokines in
      response to CRX-527 but not to LPS. We conclude that the lipid A mimetic CRX-527
      does not require the CD14 co-receptor to elicit TLR4-mediated responses.

PMID- 20039304
TI  - The A2aR adenosine receptor controls cytokine production in iNKT cells.
AB  - The purine nucleoside adenosine is an important anti-inflammatory molecule,
      inhibiting a variety of immune cells by adenosine receptor-mediated mechanisms.
      Invariant NKT (iNKT) cells recognize glycolipids presented on CD1d molecules and
      produce vigorous amounts of cytokines upon activation, hence regulating immune
      reactions. The mechanisms polarizing their cytokine pattern are elusive. Previous
      studies demonstrated that adenosine can suppress IFN-gamma production by iNKT
      cells. We describe the expression of all four known adenosine receptors A1R,
      A2aR, A2bR and A3R on mouse iNKT cells. We show that IL-4 production in primary
      mouse iNKT cells and a human iNKT line is efficiently inhibited by A2aR blockade
      with an inverse relation to IL-4. These data are supported by A2aR-deficient
      mice, which exhibit largely decreased levels of IL-4, IL-10 and TGF-beta
      concomitantly with an increase of IFN-gamma upon alpha-galactosylceramide
      administration in vivo. While A2aR inhibits other lymphocyte populations, A2aR is
      required for the secretion of IL-4 and IL-10 by iNKT cells. These data suggest
      adenosine:A2aR-mediated mechanisms can control the cytokine secretion pattern of
      iNKT cells.

PMID- 20039306
TI  - Does TLR2 regulate intestinal inflammation?
AB  - There is almost no aspect of the immune response that is not regulated by TLR.
      Initially described as drivers of the innate immune response to pathogens, it is
      now clear that the TLR family can also influence most aspects of adaptive
      immunity, as well as determine how tissue cells interact with microbes in their
      environment. In particular, the intestine and its immune system must co-exist
      with an enormous community of commensal bacteria and are also on constant alert
      against invading pathogens. Unsurprisingly, there is therefore great interest in
      how TLR might regulate physiological and pathological reactions in the gut. An
      article in this issue of the European Journal of Immunology addresses this
      question with some elegant experiments that indicate that TLR2 is not essential
      for the pathogenesis or T-cell-mediated regulation of different models of
      inflammatory bowel disease in mice.

PMID- 20039307
TI  - Extraction of organophosphorus pesticides in water and juice using ultrasound
      assisted emulsification-microextraction.
AB  - In this study, a microextraction method termed as ultrasound-assisted
      emulsification-microextraction (USAEME) has been developed for the extraction of
      organophosphorus pesticides (OPPs) in water and orange juice samples. In the
      USAEME method, aliquots of 50 microL chlorobenzene used as extraction solvent was
      added to 10 mL water sample in a conical glass centrifugal tube. Factors
      influencing the USAEME extraction efficiency such as sonication time, extraction
      solvent, extraction volume and salt addition were evaluated. Under the optimum
      conditions, enrichment factors ranged from 241 to 311, LOD varied from 5.3 to
      10.0 ng/L and linearity with a coefficient of estimation (r(2)) varied from
      0.9991 to 0.9998 in the concentration level range of 0.05-2.5 microg/L for the
      extraction of OPPs in water samples. Finally, the proposed USAEME method was used
      for the extraction of OPPs from water and orange juice. The recoveries were in
      the range of 80.0-110.0%, and the repeatability of the method expressed as RSD
      (n=3) varied between 1.6 and 13%. The USAEME method has the advantage of being
      easy to operate, low consumption of organic solvent and high extraction
      efficiency.

PMID- 20039308
TI  - Determination of volatile organic acids in tobacco by single-drop microextraction
      with in-syringe derivatization followed by GC-MS.
AB  - In this work, the novel technique based on headspace single-drop microextraction
      with in-syringe derivatization followed by GC-MS was established to determine the
      volatile organic acids in tobacco. The parameters for headspace single-drop
      microextraction and in-syringe derivatization were optimized, including
      extraction time, and volume of derivatization reagent and in-syringe
      derivatization time. The method validations including linearity, precision,
      recovery and LOD were also studied. The obtained results illustrated that the
      optimized technique was easy, highly efficient and sensitive. Finally, the
      proposed method was successfully applied to the analyses of volatile organic
      acids in tobacco samples with seven different brands. It was further demonstrated
      that the present technique developed in this study does offer a simple and fast
      approach to determine volatile organic acids in tobacco.

PMID- 20039309
TI  - Iejimalides A and B inhibit lysosomal vacuolar H+-ATPase (V-ATPase) activity and
      induce S-phase arrest and apoptosis in MCF-7 cells.
AB  - Iejimalides are novel macrolides that are cytostatic or cytotoxic against a wide
      range of cancer cells at low nanomolar concentrations. A recent study by our
      laboratory characterized the expression of genes and proteins that determine the
      downstream effects of iejimalide B. However, little is known about the cellular
      target(s) of iejimalide or downstream signaling that lead to cell-cycle arrest
      and/or apoptosis. Iejimalides have been shown to inhibit the activity of vacuolar
      H(+)-ATPase (V-ATPase) in osteoclasts, but how this inhibition may lead to cell
      cycle arrest and/or apoptosis in epithelial cells is not known. In this study,
      MCF-7 breast cancer cells were treated with iejimalide A or B and analyzed for
      changes in cell-cycle dynamics, apoptosis, lysosomal pH, cytoplasmic pH,
      mitochondrial membrane potential, and generation of reactive oxygen species. Both
      iejimalides A and B sequentially neutralize the pH of lysosomes, induce S-phase
      cell-cycle arrest, and trigger apoptosis in MCF-7 cells. Apoptosis occurs through
      a mechanism that involves oxidative stress and mitochondrial depolarization but
      not cytoplasmic acidification. These data confirm that iejimalides inhibit V
      ATPase activity in the context of epithelial tumor cells, and that this
      inhibition may lead to a lysosome-initiated cell death process.

PMID- 20039310
TI  - Effects of culture conditions on N-glycolylneuraminic acid (Neu5Gc) content of a
      recombinant fusion protein produced in CHO cells.
AB  - CHO cells express glycoproteins containing both the N-acetylneuraminic acid
      (Neu5Ac) and minor amounts of the N-glycolylneuraminic acid (Neu5Gc) forms of
      sialic acid. As Neu5Gc is not expressed in humans and can be recognized as a
      foreign epitope, there is the potential for immunogenicity issues for
      glycoprotein therapeutics. During process development of a glycosylated fusion
      protein expressed by CHO cells, a number of culture conditions were identified
      that affected the Neu5Gc content of the recombinant glycoprotein. Sodium butyrate
      (SB), a well-known additive reported to enhance recombinant protein productivity
      in specific cases, minimally affected product titers here, but did decrease
      Neu5Gc levels by 50-62%. A shift in culture temperature to a lower value after
      the exponential growth phase was used to extend the culture period. It was found
      that the Neu5Gc levels were 59% lower when the temperature shift occurred later
      near the stationary phase of the culture compared to an early-temperature shift,
      near the end of the exponential growth phase. Studies on the effects of pCO(2)
      with this product showed that the Neu5Gc levels were 46% lower at high pCO(2)
      conditions (140 mmHg) compared to moderate pCO(2) levels (20-80 mmHg). Finally, a
      comparison of sodium carbonate versus sodium hydroxide as the base used for pH
      control resulted in a reproducible 33% decrease in Neu5Gc in bioreactors using
      sodium hydroxide. These results are of practical importance as SB is a commonly
      tested additive, and the other factors affecting Neu5Gc can conveniently be used
      to reduce or control Neu5Gc in processes for the manufacture of glycoprotein
      therapeutics.

PMID- 20039311
TI  - Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone
      resorption.
AB  - Osteoclasts are unique cells that resorb bone, and are involved in not only bone
      remodeling but also pathological bone loss such as osteoporosis and rheumatoid
      arthritis. The regulation of osteoclasts is based on a number of molecules but
      full details of these molecules have not yet been understood. MicroRNAs are
      produced by Dicer cleavage an emerging regulatory system for cell and tissue
      function. Here, we examine the effects of Dicer deficiency in osteoclasts on
      osteoclastic activity and bone mass in vivo. We specifically knocked out Dicer in
      osteoclasts by crossing Dicer flox mice with cathepsin K-Cre knock-in mice. Dicer
      deficiency in osteoclasts decreased the number of osteoclasts (N.Oc/BS) and
      osteoclast surface (Oc.S/BS) in vivo. Intrinsically, Dicer deficiency in
      osteoclasts suppressed the levels of TRAP positive multinucleated cell
      development in culture and also reduced NFATc1 and TRAP gene expression. MicroRNA
      analysis indicated that expression of miR-155 was suppressed by RANKL treatment
      in Dicer deficient cells. Dicer deficiency in osteoclasts suppressed osteoblastic
      activity in vivo including mineral apposition rate (MAR) and bone formation rate
      (BFR) and also suppressed expression of genes encoding type I collagen,
      osteocalcin, Runx2, and Efnb2 in vivo. Dicer deficiency in osteoclasts increased
      the levels of bone mass indicating that the Dicer deficiency-induced osteoclastic
      suppression was dominant over Dicer deficiency-induced osteoblastic suppression.
      On the other hand, conditional Dicer deletion in osteoblasts by using 2.3 kb type
      I collagen-Cre did not affect bone mass. These results indicate that Dicer in
      osteoclasts controls activity of bone resorption in vivo.

PMID- 20039312
TI  - Differentiation of mouse embryonic stem cells into hepatocytes induced by a
      combination of cytokines and sodium butyrate.
AB  - There is increasing evidence to suggest that embryonic stem cells (ESCs) are
      capable of differentiating into hepatocytes in vitro. In this study, we used a
      combination of cytokines and sodium butyrate in a novel three-step procedure to
      efficiently direct the differentiation of mouse ESCs into hepatocytes. Mouse ESCs
      were first differentiated into definitive endoderm cells by 3 days of treatment
      with Activin A. The definitive endoderm cells were then differentiated into
      hepatocytes by the addition of acidic fibroblast growth factor (aFGF) and sodium
      butyrate to the culture medium for 5 days. After 10 days of further in vitro
      maturation, the morphological and phenotypic markers of hepatocytes were
      characterized using immunohistochemistry, immunoblotting, and reverse
      transcription-polymerase chain reaction (RT-PCR). Furthermore, the cells were
      tested for functions associated with mature hepatocytes, including glycogen
      storage and indocyanine green uptake and release, and the ratio of hepatic
      differentiation was determined by counting the percentage of albumin-positive
      cells. In the presence of medium containing cytokines and sodium butyrate,
      numerous epithelial cells resembling hepatocytes were observed, and approximately
      74% of the cells expressed the hepatic marker, albumin, after 18 days in culture.
      RT-PCR analysis and immunohistochemistry showed that these cells expressed adult
      liver cell markers, and had the abilities of glycogen storage and indocyanine
      green uptake and release. We have developed an efficient method for directing the
      differentiation of mouse ESCs into cells that exhibit the characteristics of
      mature hepatocytes. This technique will be useful for research into the molecular
      mechanisms underlying liver development, and could provide a source of
      hepatocytes for transplantation therapy and drug screening.

PMID- 20039314
TI  - Derivation of murine induced pluripotent stem cells (iPS) and assessment of their
      differentiation toward osteogenic lineage.
AB  - Induced pluripotent stem cells (iPSCs) have generated hope and excitement because
      of the potential they possess for generating patient-specific embryonic-like stem
      cells (ESCs). Although many hurdles remain to be solved before the cells can be
      applied clinically; studies directed toward understanding factors that control
      differentiation of the cells toward various cell lineages are prerequisites for
      their future application. In the present study, we generated murine iPSC and
      assessed their differentiation toward osteogenic lineage. Murine tail tip
      fibroblasts were reprogrammed into embryonic-like state by transduction with
      defined factors (Oct3/4, Sox2, c-Myc, and klf4) carried in a retroviral vector.
      The reprogrammed cells expressed ESC markers, gave rise to three germ layers as
      demonstrated by teratoma formation and immunofluorescence staining. These data
      confirmed that the reprogrammed cells exhibited ESC-like state. Treatment of
      iPSCs-derived embryoid bodies (EBs) with transforming growth factor beta 1 (TGF
      beta1) in the presence of retinoic acid enhanced generation of MSC-like cells.
      The MSCs-like cells expressed putative makers associated with MSCs; the cells
      deposited calcium in vitro when cultured in osteogenic medium. Interestingly MSCs
      like cells generated from iPSC directed EBs by treatment with retinoic acid and
      TGF-beta1 deposited more calcium in vitro than cells derived without TGF-beta1
      treatment. Taken together, the data demonstrate that iPSC give rise to MSCs-like
      state and that the cells have potential to differentiate toward osteoblasts. In
      addition, brief treatment of iPSC-derived EBs with TGF-beta1 may be an approach
      for directing iPSC toward MSC-like state.

PMID- 20039313
TI  - Bone morphogenic protein 2 directly enhances differentiation of murine osteoclast
      precursors.
AB  - Previous studies found that bone morphogenic proteins (BMPs) support osteoclast
      formation, but it is not clear whether this is a direct effect on osteoclasts or
      mediated indirectly through osteoblasts. We have shown that a mouse deficient for
      the BMP antagonist Twisted gastrulation suggested a direct positive role for BMPs
      on osteoclastogenesis. In this report, we further determine the significance of
      BMP signaling on osteoclast formation in vitro. We find that BMP2 synergizes with
      suboptimal levels of receptor activator of NF-kappaB ligand (RANKL) to enhance in
      vitro differentiation of osteoclast-like cells. The enhancement by BMP2 is not a
      result of changes in the rate of proliferation or survival of the bone marrow
      derived cultures, but is accompanied by an increase in expression of genes
      involved in osteoclast differentiation and fusion. Treatment with BMP2 did not
      significantly alter expression of RANKL or OPG in our osteoclast cultures,
      suggesting that the enhancement of osteoclastogenesis is not mediated indirectly
      through osteoblasts or stromal cells. Consistent with this, we detected
      phosphorylated SMAD1,5,8 (p-SMAD) in the nuclei of mononuclear and multinucleated
      cells in osteoclast cultures. Levels of p-SMAD, BMP2, and BMP receptors increased
      during differentiation. RNAi suppression of Type II BMP receptor inhibited RANKL
      stimulated formation of multinuclear TRAP-positive cells. The BMP antagonist
      noggin inhibited RANKL-mediated osteoclast differentiation when added prior to
      day 3, while addition of noggin on day 3 or later failed to inhibit their
      differentiation. Taken together, these data indicate that osteoclasts express
      BMP2 and BMP receptors, and that autocrine BMP signaling directly promotes the
      differentiation of osteoclasts-like cells.

PMID- 20039315
TI  - Wnt3-frizzled 1 chimera as a model to study canonical Wnt signaling.
AB  - Wnt proteins initiate signaling by binding to seven transmembrane spanning
      receptors of the frizzled (Fz) family together with the members of the low
      density lipoprotein receptor-related protein (LRP) 5 and 6. A chimera of human
      Wnt3 and Fz1 receptor was developed that efficiently activated the TCF-luciferase
      reporter. Deletion of the cytoplasmic tail and point mutations in the PDZ binding
      region in the chimera resulted in the loss of Wnt signaling, suggesting a
      critical role for the Fz cytoplasmic region in Wnt signaling. The Fz CRD is also
      critical for Wnt signaling, as a deletion of 29 amino acids in the 2nd cysteine
      loop resulted in the total loss of TCF-luciferase activation. DKK-1 protein
      blocks upregulation of the TCF-luciferase reporter by the Wnt3-Fz1 chimera,
      suggesting involvement of LRP in Wnt3-Fz1 signaling. Expression of a Wnt3-Fz1
      chimera in C3H10T1/2 cells resulted in the upregulation of alkaline phosphatase
      activity and inhibition of adipocyte formation, demonstrating that the Wnt3-Fz1
      chimera is a potent activator of differentiation of C3H10T1/2 cells into
      osteoblasts and an inhibitor of their differentiation into the adipocyte lineage.
      In summary, the Wnt-Fz chimera approach has the potential to better our
      understanding of the mechanism of Wnt action and its role, particularly in stem
      cell differentiation. In addition, this methodology can be utilized to identify
      inhibitors of either Wnt, Fz or interactors of the canonical pathway, which may
      have potential therapeutic value in the treatment of cancers and other diseases.

PMID- 20039316
TI  - Muscle atrophy in experimental cancer cachexia: is the IGF-1 signaling pathway
      involved?
AB  - Skeletal muscle wasting, one of the main features of cancer cachexia, is
      associated with marked protein hypercatabolism, and has suggested to depend also
      on impaired IGF-1 signal transduction pathway. To investigate this point, the
      state of activation of the IGF-1 system has been evaluated both in rats bearing
      the AH-130 hepatoma and in mice transplanted with the C26 colon adenocarcinoma.
      In the skeletal muscle of tumor hosts, the levels of phosphorylated (active) Akt,
      one of the most relevant kinases involved in the IGF-1 signaling pathway, were
      comparable to controls, or even increased. Accordingly, downstream targets such
      as GSK3beta, p70(S6K) and FoxO1 were hyperphosphorylated, while the levels of
      phosphorylated eIF2alpha were markedly reduced with respect to controls. In the
      attempt to force the metabolic balance toward anabolism, IGF-1 was hyperexpressed
      by gene transfer in the tibialis muscle of the C26 hosts. In healthy animals, IGF
      1 overexpression markedly increased both fiber and muscle size. As a positive
      control, IGF-1 was also overexpressed in the muscle of aged mice. In IGF-1
      hyperexpressing muscles the fiber cross-sectional area definitely increased in
      both young and aged animals, while, by contrast, loss of muscle mass or reduction
      of fiber size in mice bearing the C26 tumor were not modified. These results
      demonstrate that muscle wasting in tumor-bearing animals is not associated with
      downregulation of molecules involved in the anabolic response, and appears
      inconsistent, at least, with reduced activity of the IGF-1 signaling pathway.

PMID- 20039317
TI  - Fluorescent imaging of high-grade bladder cancer using a specific antagonist for
      chemokine receptor CXCR4.
AB  - We previously reported that the expression of CXC chemokine receptor-4 (CXCR4)
      was upregulated in invasive bladder cancers and that the small peptide T140 was a
      highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4
      expression was induced in high-grade superficial bladder tumors, including
      carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer
      cells using urinary sediments from the patients and chemically induced mouse
      bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed,
      that is a T140 derivative. TY14003 could label bladder cancer cell lines
      expressing CXCR4, whereas negative-control fluorescent peptides did not label
      them. When labeling urinary sediments from patients with invasive bladder cancer,
      positive-stained cells were identified in all patients with bladder cancer and
      positive urine cytology but not in controls. Although white blood cells in urine
      were also labeled with TY14003, they could be easily discriminated from
      urothelial cells by their shape and size. Finally, intravesical instillation of
      TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)
      induced bladder cancer model, demonstrated that fluorescent signals were detected
      in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by
      confocal microscopy and fluorescent endoscopy. On the contrary, all the normal
      bladders were found to be negative for TY14003 staining. In conclusion, these
      results indicate that TY14003 is a promising diagnostic tool to visualize small
      or flat high-grade superficial bladder cancer.

PMID- 20039318
TI  - Functional screening identifies a microRNA, miR-491 that induces apoptosis by
      targeting Bcl-X(L) in colorectal cancer cells.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNAs that negatively regulate
      expression of target mRNA. They are involved in many biological processes,
      including cell proliferation, apoptosis and differentiation, and considered as
      new therapeutic targets for cancers. In our study, we performed a gain-of
      function screen using 319 miRNAs to identify those affecting cell proliferation
      and death in human colorectal cancer cells (DLD-1). We discovered a number of
      miRNAs that increased or decreased cell viability in DLD-1. They included known
      oncogenic miRNAs such as miR-372 and miR-373, and tumor suppressive miRNAs such
      as miR-124a, but also some for which this information was novel. Among them, miR
      491 markedly decreased cell viability by inducing apoptosis. We demonstrated that
      Bcl-X(L) was a direct target of miR-491, and its silencing contributed to miR-491
      induced apoptosis. Moreover, treatment of miR-491 suppressed in vivo tumor growth
      of DLD-1 in nude mice. Our study provides a new regulation of Bcl-X(L) by miR-491
      in colorectal cancer cells, and suggests a therapeutic potential of miRNAs for
      treating colorectal cancer by targeting Bcl-X(L).

PMID- 20039319
TI  - IGF1, IGFBP1, and IGFBP3 genes and mammographic density: the Multiethnic Cohort.
AB  - Insulin-like growth factor-I (IGF-I) has mitogenic properties and stimulates cell
      growth. In this analysis, we investigated the relation between common genetic
      variation in IGF1, IGFBP1, and IGFBP3, and mammographic density among 819 women
      of Hawaiian, European, and Japanese ancestry from the Multiethnic Cohort Study.
      Mammographic density was assessed using a quantitative computer-assisted method.
      Previously identified tag single nucleotide polymorphisms (SNPs) for IGF1 (26 tag
      SNPs) and IGFBP1/IGFBP3 (22 tag SNPs) were genotyped among the 819 women. Mixed
      models were conducted to evaluate the associations between genetic variation and
      mammographic density. Two SNPs were borderline statistical significantly
      associated with mammographic density: rs35539615 on IGFBP1 (p = 0.05) and
      rs2453839 on IGFBP3 (p = 0.01). Rs35767on IGF1 (p = 0.03) was also associated
      with mammographic density, although in opposite direction of what was expected
      from previous findings with IGF-I levels. The majority of SNPs were, however, not
      associated with mammographic density. Analyses stratified by ethnicity showed
      similar results as the overall analyses for IGF1 and IGFBP1. However, for 4 SNPs
      in the IGFBP3 gene, the minor allele was associated with lower mammographic
      density in Japanese Americans and higher mammographic density in Caucasians.
      Given the large number of SNPs tested and the few borderline significant results,
      we only found weak evidence that genetic variations in IGFBP1 or IGFBP3 may be
      related to mammographic density. Ethnicity may modify these relations.

PMID- 20039320
TI  - Transient depletion of CD4(+) T cells augments IL-21-based immunotherapy of
      disseminated neuroblastoma in syngeneic mice.
AB  - IL-21 is a member of the IL-2 cytokine family, produced by CD4+ T cells. We
      previously showed that immunotherapy (IT) with IL-21-transduced neuroblastoma
      cells (Neuro2a/IL-21) cured 33% of syngeneic mice bearing systemic NB. Here, we
      studied whether the removal of Treg cells could potentiate the therapeutic
      efficacy of Neuro2a/IL-21 vaccine. The administration of anti-CD25 mAb, which
      targets Treg cells, slightly potentiated the effect of vaccine IT (50% cure
      rate), but anti-CD4 mAb had a more potent effect leading to 80% cure rate. Anti
      CD25 mAb, indeed, only partially depleted CD4+CD25+FoxP3+ Treg cells, whereas
      anti-CD4 mAb was more effective in this respect, leading to 90% depletion of Treg
      cells. In mice receiving vaccine+anti-CD4 mAb, which developed systemic immunity
      to NB, CD4+ T cells counts completely recovered in 90 days. Depletion of CD8+ T
      cells abrogated the effect of the combined IT, indicating a predominant role of
      these cells in driving the immune response. In addition, CD8+ T cells from cured
      mice coinjected with Neuro2a/parental cells (pc) in NOD-SCID mice completely
      inhibited tumor growth. Spleen cells from mice receiving Neuro2a/IL-21
      vaccination showed increased expression of IFN-alpha2, -beta1 and -gamma mRNA.
      Moreover, mice receiving vaccine therapy alone or vaccine+anti-CD4 mAb showed
      increased IFN-gamma serum levels and IFN-gamma-producing CD8+ T cells were found
      in spleen cells. In conclusion, anti-CD4 mAb potentiated IL-21-based IT by
      removing Treg cells and/or their precursors and other potentially immune
      suppressive CD4+ cell subsets, thus allowing the development of an IL-21-driven
      CD8+ T cell response, which mediates NB rejection.

PMID- 20039321
TI  - Association between antibiotic use and risk of prostate cancer.
AB  - The association between antibiotics and risk of cancer has been addressed in
      different studies, most of which were addressing breast cancer. The objective of
      this study was to assess the association between antibiotics use and risk of
      prostate cancer. We carried out a population-based case-control study using data
      from Saskatchewan Health administrative databases (Canada) between the years 1981
      and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4
      controls, using incidence density sampling. The effect of dosage and timing of
      antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer
      risk was assessed. Number of prescriptions and number of tablets were used as
      exposure definitions. Moreover, the effect of different classes of antibiotics on
      prostate cancer was also studied. A total of 4,052 prostate cancer cases and
      16,208 matched controls were included in this study. Antibiotics exposure (number
      of prescriptions) during the period of 1-15 years in the past was significantly
      associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and
      2.83 for the 4 quartiles, respectively, p-trend = 0.0001. When number of units
      was taken as the exposure definition, similar results were found. We did not find
      any effect of the timing or class of antibiotic exposure on prostate cancer risk.
      We found a dose-dependent association between antibiotics exposure up to 15 years
      in the past and risk of prostate cancer. However, the lack of temporal trends and
      the absence of class specific effects suggest a noncausal relationship.

PMID- 20039322
TI  - The role of Eph receptors and ephrin ligands in colorectal cancer.
AB  - Eph receptors and their ephrin ligands constitute the largest subfamily of
      receptor tyrosine kinases and are components of the cell signaling pathways
      involved during development. Eph and ephrin overexpression have been documented
      in a variety of human cancers including gastrointestinal malignancies and in
      particular colorectal malignancies. EphB and ephrin B proteins have been
      implicated in the homeostasis of the gastrointestinal tract where EphB2- and
      EphB3-ephrin B signaling regulates cell sorting in the mature epithelium. These
      proteins are also reported to be upregulated in colon carcinomas. The EphA/ephrin
      A system has also been implicated in epithelial tissue structure and function.
      More recently, EphA receptors and their corresponding ligands have been
      implicated in numerous malignancies. Of these, EphA2 in particular has been
      intensively investigated and has been proposed as a therapeutic target. An
      interesting observation emerging from these studies is the role for Ephs and
      ephrins in critical aspects of cell adhesion, migration and positioning, and a
      crucial role in tumor progression and metastasis. However, the underlying role of
      Ephs and ephrins in these processes has generally been studied on individual Eph
      or ephrin genes. Given the multiplicity of Eph expression on gut epithelial
      cells, a more global approach is needed to define the precise role of Eph-ephrin
      interaction in malignant transformation. Here, we will review the recent advances
      on the role of Eph-ephrin signaling in colorectal malignancies.

PMID- 20039323
TI  - Prevalence of type-specific human papillomavirus in endocervical, upper and lower
      vaginal, perineal and vaginal self-collected specimens: Implications for vaginal
      self-collection.
AB  - To determine why a vaginal self-collection tested for high-risk human
      papillomavirus (HR-HPV) by Hybrid Capture 2(R) (hc2) has lower sensitivity and
      specificity for cervical intraepithelial neoplasia Grade 2 or worse (> or = CIN
      2), we collected 5 specimens (endocervix, upper and lower vagina, perineum,
      vaginal self-collection) from 2,625 women. Endocervical and self-collected
      specimens had HR-HPV tests by hc2. All 5 anogenital specimens were tested for 37
      HPV genotypes [Linear Array(R), (LA)] from 397 women hc2 positive in endocervical
      or self-collected specimens and for a randomly selected 71 of 2,228 women hc2
      negative on both specimens. Three hundred nintey-five women who screened positive
      by hc2 or had abnormal cytology underwent colposcopic evaluation. Of 47 women
      with > or = CIN 2, hc2 was positive in 97.9% (46/47) of endocervical and 80.9%
      (38/47), p = 0.008 of self-collected specimens. Seven of 9 women with > or = CIN
      2 and negative self-collected hc2 tests were positive for HR-HPV by LA. Of 2,578
      women without > or = CIN 2, hc2 was positive in 9.8% (253/2,578) of endocervical
      and 11.4% (294/2,578), p = 0.001 of self-collected specimens. Of the 41 more
      women without > or = CIN 2 that tested hc2 positive on the self-collected but
      negative on endocervical specimen, LA tested positive for HR-HPV in 24, negative
      for HPV in 11 and negative for HR-HPV but positive for low-risk HPV in 6. Lower
      sensitivity of self-collected specimens is secondary to lower levels of vaginal
      HR-HPV. The principal cause of the lower specificity of self-collected specimens
      is HR-HPV present solely in the vagina, which is not associated with > or = CIN
      2.

PMID- 20039324
TI  - Detoxification of aristolochic acid I by O-demethylation: less nephrotoxicity and
      genotoxicity of aristolochic acid Ia in rodents.
AB  - Ingestion of aristolochic acids (AA) contained in herbal remedies results in
      aristolochic acid nephropathy (AAN), which is characterized by chronic renal
      failure, tubulointerstitial fibrosis and urothelial cancer. AA I and AA II,
      primary components in AA, have similar genotoxic potential, whereas only AA I
      shows severe renal toxicity in rodents. AA I is demethylated to form 8-hydroxy
      aristolochic acid I (AA Ia) as a major metabolite. However, the nephrotoxicity
      and genotoxicity of AA Ia has not yet been determined. AA Ia was isolated from
      urine collected from rats treated with AA I and characterized by NMR and mass
      spectrometry. The purified AA Ia was administered intraperitoneally to C3H/He
      male mice for 9 days and its toxicity was compared with AA I. Using (32)P
      postlabeling/polyacrylamide gel electrophoresis, the level of AA Ia-derived DNA
      adducts in renal cortex was approximately 70-110 times lower than that observed
      with AA I, indicating that AA Ia has only a limited genotoxicity. Supporting this
      result, when calf thymus DNA was reacted with AA Ia in a buffer containing zinc
      dust, the formation of AA Ia-DNA adducts was two-orders of magnitude lower than
      that of AA I. Histopathologic analysis revealed that unlike AA I, no significant
      changes were detected in the renal cortex of mice treated with AA Ia. Therefore,
      the contribution of AA Ia to renal toxicity is minimum. We conclude the metabolic
      pathway of converting AA I to AA Ia functions as the detoxification of AA I.

PMID- 20039325
TI  - Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in
      the E3N-EPIC study.
AB  - Evidence of a protective effect of fruit and vegetable intake on breast cancer
      risk is inconsistent. Epidemiologic cohort studies based on blood carotenoid
      intakes as biomarkers of consumption of fruits and vegetable in individuals are
      still scare and findings are discrepant. The study population included women in
      the E3N Study, the large French component of the European Prospective
      Investigation into Cancer and Nutrition (EPIC). During an average of 7 years
      follow-up, 366 cases of incident invasive breast cancer (84 premenopausal women
      and 282 postmenopausal women) among 19,934 women who completed a dietary
      questionnaire and had available blood samples at baseline (1995-1998) were
      included in the study. Controls were randomly matched on age, menopausal status
      at blood collection, fasting status at blood collection, date and collection
      center. Serum carotenoids, tocopherols and retinol concentrations were assessed
      by high pressure liquid chromatography. Odds ratios for breast cancer risk
      adjusted for established breast cancer risk factors were calculated by quintile
      of serum micronutrient concentrations. No significant associations between breast
      cancer risk and serum carotenoids (highest versus lowest quintile, odds ratio
      (OR) = 0.74, 95% confidence interval (CI) = 0.47-1.16, p for trend 0.38),
      tocopherols (OR = 0.68, 95% CI = 0.41-1.10, p for trend 0.26) and retinol (OR =
      0.85, 95% CI = 0.53-1.35, p for trend 0.34) were found. Our findings did not
      support the hypothesis that lipophilic antioxidant micronutrients found in fruits
      and vegetables protect against breast cancer, at least in postmenopausal women.

PMID- 20039327
TI  - Conservation education and primates: twenty-first century challenges and
      opportunities.
AB  - Conservation Education has gone through a transformation since it was originally
      introduced. Numerous primatologists, working in all regions of the world where
      primates are endemic, have been extremely proactive in the application of
      Conservation Education (CE) and CE principles in their work. Here, I discuss the
      ongoing threats to primate populations around the world. Finally, I introduce a
      framework that can guide primatologists, as we move forward and face the
      challenges of the twenty-first century.

PMID- 20039326
TI  - Analysis of anti-proliferative and chemosensitizing effects of sunitinib on human
      esophagogastric cancer cells: Synergistic interaction with vandetanib via
      inhibition of multi-receptor tyrosine kinase pathways.
AB  - The receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and
      vascular endothelial growth factor receptor 1-3 (VEGFR1-3), are frequently
      expressed in gastric cancer and are putative therapeutic targets in this disease.
      We have investigated the anti-proliferative and chemosensitizing properties of
      the multitargeted small-molecule RTK inhibitors sunitinib and vandetanib in a
      panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance,
      the expression of potential targets of these small-molecule inhibitors was
      examined by reverse transcriptase-polymerase chain reaction, western blotting,
      and flow cytometry. EGFR mRNA and protein was detected in all cases, with VEGFR2
      expression noted in all but 1 line. Both EGF and VEGF were shown to stimulate
      tumor cell growth, and both sunitinib and vandetanib were found to be associated
      with significant dose-dependent inhibition of proliferation and an enhancement of
      apoptosis, as determined by MTT and propidium iodide/Annexin V labeling assays,
      respectively. The addition of sunitinib to VEGF-stimulated NCI-N87 cells was
      associated with a reduction in MAPK phosphorylation (pMAPK) but not Akt
      phosphorylation (pAkt), whereas the addition of vandetanib was associated with
      reductions in both VEGF- and EGF-mediated VEGFR2 phosphorylation, pMAPK and pAkt.
      Co-administration of sunitinib significantly enhanced the sensitivity of MKN-45
      cells to cisplatin and irinotecan. In addition, vandetanib synergistically
      enhanced the sunitinib-associated inhibition of gastric cancer cell growth. In
      conclusion, these preliminary data confirm the importance of EGFR and VEGFR
      signaling in gastric cancer and suggest that the simultaneous inhibition of RTK
      pathways through sunitinib and vandetanib may provide therapeutic benefit in this
      disease.

PMID- 20039328
TI  - Effects of reproductive condition and dominance rank on cortisol responsiveness
      to stress in free-ranging female rhesus macaques.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis modulates individuals'
      physiological responses to social stress, which is an inevitable aspect of the
      daily lives of group-living animals. Previous nonhuman primate studies have
      reported that sex, age, rank, and reproductive condition influence cortisol
      levels under stressful conditions. In this study we investigated cortisol
      responses to stress among 70 multiparous, free-ranging female rhesus macaques
      (Macaca mulatta) on the island of Cayo Santiago, PR. Plasma cortisol samples were
      collected in two consecutive years under similar conditions. Twenty-two females
      were sampled both years, and most of those females were lactating in only one of
      the years. Individual differences in cortisol levels were stable across years,
      even though reproductive condition changed for most individuals. No relationship
      was found between age or social rank and cortisol levels. Of the females that
      changed reproductive conditions, cortisol levels were higher when they were
      lactating than when they were cycling, and the amount of change in cortisol from
      cycling to lactating was greatest for low-ranking individuals. Heightened
      reactivity to stress during lactation may be the result of concerns about infant
      safety, and such concerns may be higher among low-ranking mothers than among
      higher ranking mothers. Psychosocial stress and hyperactivation of the HPA axis
      during lactation can suppress immune function and increase vulnerability to
      infectious diseases, thus explaining why adult females in the free-ranging rhesus
      macaque population on Cayo Santiago have a higher probability of mortality during
      the birth season than during the mating season.

PMID- 20039329
TI  - The species-area relationship and confounding variables in a threatened monkey
      community.
AB  - This study investigates the species-area relationship (SAR) for forest monkeys in
      a biodiversity hotspot. The Udzungwa Mountains of Tanzania are well-suited to
      investigate the SAR, with seven monkey species in a range of fragment sizes (0.06
      526 km(2)). We test the relationship between species richness and forest fragment
      size, relative to human and environmental factors. We distinguish resident and
      transitory species because the latter have an "effective patch size" beyond the
      area of forest. Forest area was the strongest (log-linear) predictor of species
      richness. However, forest area, elevation range and annual moisture index were
      intercorrelated. Previous knowledge of the relationship between elevation and
      tree communities suggests that the SAR is largely a result of habitat
      heterogeneity. Isolation by farmland (matrix habitat) also had a significant
      negative effect on species richness, probably exacerbated by hunting in small
      forests. The effect of area and isolation was less for transitory species. The
      human influence on species' presence/absence was negatively related to the extent
      of occurrence. Weaker relationships with temperature and precipitation suggest
      underlying climatic influences, and give some support for the influence of
      productivity. A reduced area relationship for smaller forests suggests that
      fragment sizes below 12-40 km(2) may not be reliable for determining SAR in
      forest monkeys. Further practical implications are for management to encourage
      connectivity, and for future SAR research to consider residency, matrix
      classification and moisture besides precipitation.

PMID- 20039330
TI  - Conservation education in Madagascar: three case studies in the biologically
      diverse island-continent.
AB  - Few Malagasy children and adults are aware of the rare and unique fauna and flora
      indigenous to their island-continent, including flagship lemur species. Even the
      Malagasy ancestral proverbs never mentioned lemurs, but these same proverbs
      talked about the now extinct hippopotamus. Madagascar's geography, history, and
      economic constraints contribute to severe biodiversity loss. Deforestation on
      Madagascar is reported to be over 100,000 ha/year, with only 10-15% of the island
      retaining natural forest [Green & Sussman, 1990]. Educating children, teacher
      training, and community projects about environmental and conservation efforts to
      protect the remaining natural habitats of endangered lemur species provide a
      basis for long-term changes in attitudes and practices. Case studies of three
      conservation education projects located in different geographical regions of
      Madagascar, Centre ValBio, Madagacar Wildlife Conservation Alaotra Comic Book
      Project, and The Ako Book Project, are presented together with their ongoing
      stages of development, assessment, and outcomes. We argue that while
      nongovernmental organizational efforts are and will be very important, the
      Ministry of Education urgently needs to incorporate biodiversity education in the
      curriculum at all levels, from primary school to university.

PMID- 20039331
TI  - Angioarchitecture of squamous cell carcinoma from hamster buccal pouch: a
      scanning electron microscopy study.
AB  - Tumoral angiogenesis has been widely studied by histochemical analysis but little
      has been done regarding morphology of these new vessels. The objective of this
      study was to perform a qualitative analysis of the angiogenic response to
      chemical induction with dimethylbenzanthracene (DMBA) and carbamide peroxide of
      squamous cell carcinoma in pouches of Syrian hamsters after different periods of
      treatment. Twenty-four Syrian golden hamsters, divided into three groups of eight
      animals each, had their right jugal pouches treated with a 5% DMBA solution three
      times a week and a 10% carbamide peroxide two times a week for 55, 70 and 90
      days. The left pouch was considered the control. After tumor induction, five
      animals in each group had their pouches prepared for analysis under scanning
      electron microscopy and three animals for analysis under light microscopy. The
      control pouches showed a vascular system composed by few main vessels running
      parallel to the longest axis of the pouch with some branches. In the pouches
      submitted to tumor induction, a well-differentiated squamous cell carcinoma was
      present since 55 days induction in all samples. The new vascular system showed
      the presence of many tortuous vessels and the majority of them were veins and
      capillaries. Terminal loops were extremely sinuous adopting a glomerular or
      corkscrew shape. These tumor vessels are different from normal vessels,
      presenting irregular diameters, outpouchings and constrictions. Angiogenesis of
      sprouting and intussusceptive kind could be identified in the tumor pouches, and
      they were more frequent as the tumor developed.

PMID- 20039332
TI  - How a heavy-bodied snake strikes quickly: high-power axial musculature in the
      puff adder (Bitis arietans).
AB  - Despite being large, heavy-bodied snakes, puff adders (Bitis arietans) are
      capable of achieving strike velocities and accelerations similar to, or greater
      than, those of much smaller snakes (means of 2.6 and 72 m/sec(2), respectively).
      The mechanistic basis of the strike was examined using high-speed digital
      videography, coupled with electromyographic (EMG) analysis, of the two main
      extensors of the vertebral column, the semispinalis and longissimus. Although the
      strike involves the rapid extension of preformed body curves, the extensor
      muscles were not electrically active during body extension. The vertebral
      extensor muscles exhibited bursts of electrical activity before the onset of
      movement-and quantified features of these EMG signals were significantly related
      to kinematic aspects of the strike (e.g., acceleration)-however, this electrical
      activity terminated shortly (approximately 50 msec) before the onset of movement.
      It is hypothesized that the prestrike activity of the extensor muscles functions
      to place the (extensive) musculo-tendon complex of the snake's epaxial muscles
      under tension, and that the displacement of the body during the strike is due to
      the elastic recoil of this musculo-tendon complex. Incorporation of this type of
      elastic recoil would increase the power output of the vertebral extensors. Power
      amplification of the vertebral extensors may be an evolutionary necessity if a
      large, heavy-bodied snake, like B. arietans, is going to achieve rapid
      acceleration during the strike.

PMID- 20039333
TI  - Screening for cancer.

PMID- 20039335
TI  - Multifunctional imaging nanoprobes.
AB  - Multifunctional imaging nanoprobes have proven to be of great value in the
      research of pathological processes, as well as the assessment of the delivery,
      fate, and therapeutic potential of encapsulated drugs. Moreover, such probes may
      potentially support therapy schemes by the exploitation of their own physical
      properties, e.g., through thermal ablation. This review will present four classes
      of nanoparticulate imaging probes used in this area: multifunctional probes (1)
      that can be tracked with at least three different and complementary imaging
      techniques, (2) that carry a drug and have bimodal imaging properties, (3) that
      are employed for nucleic acid delivery and imaging, and (4) imaging probes with
      capabilities that can be used for thermal ablation. We will highlight several
      examples where the suitable combination of different (bio)materials like
      polymers, inorganic nanocrystals, fluorophores, proteins/peptides, and lipids can
      be tailored to manufacture multifunctional probes to accomplish nanomaterials of
      each of the aforementioned classes. Moreover, it will be demonstrated how
      multimodality imaging approaches improve our understanding of in vivo
      nanoparticle behavior and efficacy at different levels, ranging from the
      subcellular level to the whole body.

PMID- 20039336
TI  - Development of a multiresidue method for the determination of multiclass
      pesticides in soil using GC.
AB  - The principal objective of the present study was to develop a multiresidue
      analytical method for 62 pesticides in a soil matrix. Soil samples were fortified
      with known quantities of pesticides at two different concentration levels (0.1
      and 0.01 microg/g) and the analytes were extracted via a liquid-solid extraction
      method. The pesticides were separated on an HP5 capillary column and were
      detected by gas chromatography coupled to an electron capture detector (GC-ECD).
      The method was validated, considering its good linearities (r(2) = 0.978-0.999),
      specificity and recovery characteristics. Recoveries were found between 70.3 and
      113.4% for all pesticides except edifenphos (67.5%) and dichlobenil (69.5%)
      spiked at a 0.1 microg/mL concentration level and 74.5-117% except ethalfluralin
      (63.3%) and dichlobenil (51.9%) spiked at a concentration of 0.01 microg/mL. The
      developed method could be utilized as a simple and cost-effective method for the
      routine analysis of 62 pesticides in soil samples.

PMID- 20039337
TI  - High-performance liquid chromatography with diode array detection coupled to
      electrospray time-of-flight and ion-trap tandem mass spectrometry to identify
      phenolic compounds from a Cistus ladanifer aqueous extract.
AB  - INTRODUCTION: Cistus ladanifer is an aromatic shrub that is widespread in the
      Mediterranean region. The labdanum exudate is used in the fragrance industry and
      has been characterised. However, there is not enough information about the
      phenolic content of the raw plant, the aerial part of it being a very rich source
      of bioactive compounds. OBJECTIVE: Characterisation of the bioactive compounds of
      the raw plant and its aerial parts. METHODOLOGY: High-performance liquid
      chromatography with diode array and electrospray ionisation mass spectrometric
      detection was used to carry out the comprehensive characterisation of a Cistus
      ladanifer shrub aqueous extract. Two different MS techniques were coupled to
      HPLC: time-of-flight mass spectrometry and tandem mass spectrometry. RESULTS:
      Many well-known compounds present in Cistus ladanifer were characterised, such as
      flavonoids, phenolic acids, ellagitanins, hexahydroxydiphenoyl and derivatives,
      and other compounds. CONCLUSION: The method described simultaneously separated a
      wide range of phenolic compounds and the proposed characterisation of the major
      compounds of this extract was carried out. It is important to highlight that, to
      our knowledge, this is the first time that a Cistus ladanifer aqueous extract
      from the raw plant has been characterised.

PMID- 20039338
TI  - Integrated methodology for the evaluation of cleaning effectiveness in two
      Russian icons (16th-17th centuries).
AB  - This article covers a methodology for evaluating the effectiveness of cleaning
      two Russian icons. The icons belong to a group of five from the same iconographic
      school, dating from the 16th to 17th centuries. An integrated and complementary
      approach to varnish and overpaint removal involved microscopic techniques
      (optical and scanning electron microscopy) and colorimetry (CIE L*a*b* system).
      The materials and techniques used in these icons have been characterized
      previously. Cleaning revealed extensive overpainting that had not only
      dramatically changed the original appearance, but also the meaning and
      attribution of one of the two icons. The analyses carried out were useful in
      determining the extent of the overpainting and led to a better assessment of the
      results and effectiveness of the restoration.

PMID- 20039339
TI  - Ionic liquids based on azolate anions.
AB  - Compartmentalized molecular level design of new energetic materials based on
      energetic azolate anions allows for the examination of the effects of both cation
      and anion on the physiochemical properties of ionic liquids. Thirty one novel
      salts were synthesized by pairing diverse cations (tetraphenylphosphonium,
      ethyltriphenylphosphonium, N-phenyl pyridinium, 1-butyl-3-methylimidazolium,
      tetramethyl-, tetraethyl-, and tetrabutylammonium) with azolate anions (5
      nitrobenzimidazolate, 5-nitrobenzotriazolate, 3,5-dinitro-1,2,4-triazolate, 2,4
      dinitroimidazolate, 4-nitro-1,2,3-triazolate, 4,5-dinitroimidazolate, 4,5
      dicyanoimidazolate, 4-nitroimidazolate, and tetrazolate). These salts have been
      characterized by DSC, TGA, and single crystal X-ray crystallography. The azolates
      in general are surprisingly stable in the systems explored. Ionic liquids were
      obtained with all combinations of the 1-butyl-3-methylimidazolium cation and the
      heterocyclic azolate anions studied, and with several combinations of tetraethyl-
      or tetrabutylammonium cations and the azolate anions. Favorable structure
      property relationships were most often achieved when changing from 4- and 4,5
      disubstituted anions to 3,5- and 2,4-disubstituted anions. The most promising
      anion for use in energetic ionic liquids of those studied here, was 3,5-dinitro
      1,2,4-triazolate, based on its contributions to the entire set of target
      properties.

PMID- 20039340
TI  - Phenacyl-thiophene and quinone semiconductors designed for solution
      processability and air-stability in high mobility n-channel field-effect
      transistors.
AB  - Electron-transporting organic semiconductors (n-channel) for field-effect
      transistors (FETs) that are processable in common organic solvents or exhibit air
      stable operation are rare. This investigation addresses both these challenges
      through rational molecular design and computational predictions of n-channel FET
      air-stability. A series of seven phenacyl-thiophene-based materials are reported
      incorporating systematic variations in molecular structure and reduction
      potential. These compounds are as follows: 5,5'''-bis(perfluorophenylcarbonyl)
      2,2':5',- 2'':5'',2'''-quaterthiophene (1), 5,5'''-bis(phenacyl)-2,2':5',2'':
      5'',2'''-quaterthiophene (2), poly[5,5'''-(perfluorophenac-2-yl)-4',4''-dioctyl
      2,2':5',2'':5'',2'''-quaterthiophene) (3), 5,5'''-bis(perfluorophenacyl)-4,4'''
      dioctyl-2,2':5',2'':5'',2'''-quaterthiophene (4), 2,7-bis((5
      perfluorophenacyl)thiophen-2-yl)-9,10-phenanthrenequinone (5), 2,7-bis[(5
      phenacyl)thiophen-2-yl]-9,10-phenanthrenequinone (6), and 2,7-bis(thiophen-2-yl)
      9,10-phenanthrenequinone, (7). Optical and electrochemical data reveal that
      phenacyl functionalization significantly depresses the LUMO energies, and
      introduction of the quinone fragment results in even greater LUMO stabilization.
      FET measurements reveal that the films of materials 1, 3, 5, and 6 exhibit n
      channel activity. Notably, oligomer 1 exhibits one of the highest mu(e) (up to
      approximately = 0.3 cm(2) V(-1) s(-1)) values reported to date for a solution
      cast organic semiconductor; one of the first n-channel polymers, 3, exhibits
      mu(e) approximately = 10(-6) cm(2) V(-1) s(-1) in spin-cast films (mu(e)=0.02
      cm(2) V(-1) s(-1) for drop-cast 1:3 blend films); and rare air-stable n-channel
      material 5 exhibits n-channel FET operation with mu(e)=0.015 cm(2) V(-1) s(-1),
      while maintaining a large I(on:off)=10(6) for a period greater than one year in
      air. The crystal structures of 1 and 2 reveal close herringbone interplanar pi
      stacking distances (3.50 and 3.43 A, respectively), whereas the structure of the
      model quinone compound, 7, exhibits 3.48 A cofacial pi-stacking in a slipped,
      donor-acceptor motif.

PMID- 20039341
TI  - Self-assembly of ureido-pyrimidinone dimers into one-dimensional stacks by
      lateral hydrogen bonding.
AB  - Ureido-pyrimidinone (UPy) dimers substituted with an additional urea
      functionality self-assemble into one-dimensional stacks in various solvents
      through lateral non-covalent interactions. (1)H NMR and DOSY studies in CDCl(3)
      suggest the formation of short stacks (<10), whereas temperature-dependent
      circular dichroism (CD) studies on chiral UPy dimers in heptane show the
      formation of much larger helical stacks. Analysis of the concentration-dependent
      evolution of chemical shift in CDCl(3) and the temperature-dependent CD effect in
      heptane suggest that this self-assembly process follows an isodesmic pathway in
      both solvents. The length of the aggregates is influenced by substituents
      attached to the urea functionality. In sharp contrast, UPy dimers carrying an
      additional urethane group do not self-assemble into ordered stacks, as is evident
      from the absence of a CD effect in heptane and the concentration-independent
      chemical shift of the alkylidene proton of the pyrimidinone ring in CDCl(3).

PMID- 20039342
TI  - A convergent general strategy for the functionalized 2-aryl cycloalkyl-fused
      chromans: intramolecular hetero-Diels-Alder reactions of ortho-quinone methides.

PMID- 20039343
TI  - Cluster-based self-assembly route toward MoO3 single-walled nanotubes.
AB  - MoO(3) has a unique rigid double-layer structure, which makes it a real challenge
      to prepare nanotubular structures. The controlled synthesis of MoO(3) single
      walled nanotubes (SWNTs) is achieved through a cluster-based self-assembly route
      on the dodecanethiol/water interface. Various factors are studied at length,
      including precursor type, reaction time, temperature, pH value, and their
      influence on the morphology of products. The concept of "self-assembly-from
      simple clusters to nanostructures" is proposed here based on preliminary results
      from the synthesis of MoO(3) SWNTs, which provides a new aspect for traditional
      synthetic chemistry of nanomaterials and polyoxometalates.

PMID- 20039344
TI  - Synthesis and affinity evaluation of a small library of bidentate cholera toxin
      ligands: towards nonhydrolyzable ganglioside mimics.
AB  - A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose
      and sialic acid as pharmacophoric carbohydrate residues, was synthesized and
      tested. All compounds were synthesized from readily available precursors using
      high-performance reactions, including click chemistry protocols, and avoiding O
      glycosidic bonds. Some of the most active molecules also feature a point of
      further derivatization that can be used for conjugation with polyvalent aglycons.
      Their affinity towards cholera toxin was assessed by weak affinity
      chromatography, which allowed a systematic evaluation and selection of the best
      candidates. Affinity could be enhanced up to one or two orders of magnitude over
      the affinity of the individual pharmacophoric sugar residues.

PMID- 20039345
TI  - A panchromatic supramolecular fullerene-based donor-acceptor assembly derived
      from a peripherally substituted bodipy-zinc phthalocyanine dyad.
AB  - A panchromatic 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-zinc phthalocyanine
      conjugate (Bodipy-ZnPc) 1 was synthesized starting from phthalocyanine aldehyde
      4, via dipyrromethane 3 and dipyrromethene 2. Conjugate 1 represents the first
      example in which a Bodipy unit is tethered to the peripheral position of a
      phthalocyanine core. Electrochemical and optical measurements provided evidence
      for strong electronic interactions between the Bodipy and ZnPc constituents in
      the ground state of 1. When conjugate 1 is subjected to photoexcitation in the
      spectral region corresponding to the Bodipy absorption, the strong fluorescence
      characteristic of the latter subunit is effectively quenched (i.e., > or = 97%).
      Excitation spectral analysis confirmed that the photoexcited Bodipy and the
      tethered ZnPc subunits interact and that intraconjugate singlet energy transfer
      occurs with an efficiency of ca. 25%. Treatment of conjugate 1 with N
      pyridylfulleropyrrolidine (8), an electron-acceptor system containing a nitrogen
      ligand, gives rise to the novel electron donor-acceptor hybrid 1<-->8 through
      ligation to the ZnPc center. Irradiation of the resulting supramolecular ensemble
      within the visible range leads to a charge-separated Bodipy-ZnPc(*+)-C(60)(*-)
      radical-ion-pair state, through a sequence of excited-state and charge transfers,
      characterized by a remarkably long lifetime of 39.9 ns in toluene.

PMID- 20039346
TI  - Platinum nanoparticles: the crucial role of crystal face and colloid stabilizer
      in the diastereoselective hydrogenation of cinchonidine.
AB  - The preparation of stable metal nanoparticles requires a strong interaction
      between the (organic) stabilizer and the metal surface that might alter the
      catalytic properties. This behavior has been described as "poisoning" since the
      stabilizer normally decreases the catalytic activity due to site blocking. Here
      we show a striking influence of the stabilizer on the selectivity in the
      hydrogenation of cinchonidine (CD) over poly(acrylic acid) (PAA)-stabilized Pt
      nanoparticles with well-defined shape distributions. In the hydrogenation of the
      heteroaromatic ring of cinchonidine in toluene, the diastereomeric excess of the
      (S)-hexahydrocinchonidine increased upon increasing Pt{111}/Pt{100} ratio, but
      this distinct shape selectivity was observed only after the oxidative removal of
      PAA at 473 K. The use of the as-prepared nanoparticles inverted the major
      diastereomer to R, and this isomer was formed also in acetic acid. This striking
      change in the diastereoselectivity indicates that poly(acrylic acid), which
      remains on the Pt surface after preparation, interacts with CD during
      hydrogenation almost as strongly as the solvent acetic acid. The PAA stabilizer
      plays a dual role: it allows one to control the size and shape of the
      nanoparticles during their synthesis, and it affects the rate and
      diastereoselectivity of the hydrogenation of CD probably through a "surface
      localized acidification".

PMID- 20039347
TI  - Multifunctional magnetic materials obtained by insertion of a spin-crossover
      Fe(III) complex into bimetallic oxalate-based ferromagnets.
AB  - The syntheses, structures and magnetic properties of the compounds of formula
      [Fe(III)(sal(2)-trien)][Mn(II)Cr(III)(ox)(3)].CH(2)Cl(2) (1; H(2)sal(2)
      trien=N,N'-disalicylidenetriethylenetetramine, ox=oxalate), [Fe(III)(sal(2)
      trien)][Mn(II)Cr(III)(ox)(3)].CH(3)OH (2), [In(III)(sal(2)
      trien)][Mn(II)Cr(III)(ox)(3)].0.25H(2)O.0.25CH(3)OH.0.25CH(3)CN (3), and
      [In(III)(sal(2)-trien)][Mn(II)Cr(III)(ox)(3)].CH(3)NO(2).0.5H(2)O (4) are
      reported. The structure of 1 presents a 2D honeycomb anionic layer formed by
      Mn(II) and Cr(III) ions linked through oxalate ligands and a cationic layer of
      [Fe(sal(2)-trien)](+) complexes intercalated between the 2D oxalate network. The
      structures of 2, 3, and 4 present a 3D achiral anionic network formed by Mn(II)
      and Cr(III) ions linked through oxalate ligands with [Fe(sal(2)-trien)](+) or
      [In(sal(2)-trien)](+) complexes and solvent molecules intercalated within the 3D
      oxalate network. The magnetic properties and Mossbauer spectroscopy of 1 and 2
      indicate that these compounds undergo a long-range ferromagnetic ordering at
      around 5 K and a spin crossover of the intercalated [Fe(sal(2)-trien)](+)
      complexes above 130 K, which is complete in the case of 1. The magnetic
      properties of the compounds 3 and 4 confirm the ferromagnetic ordering of the
      bimetallic oxalate network.

PMID- 20039348
TI  - Gold(I)-catalyzed glycosylation with glycosyl ortho-alkynylbenzoates as donors:
      general scope and application in the synthesis of a cyclic triterpene saponin.
AB  - Glycosyl ortho-alkynylbenzoates have emerged as a new generation of donors for
      glycosidation under the catalysis of gold(I) complexes such as Ph(3)PAuOTf and
      Ph(3)PAuNTf(2) (Tf = trifluoromethanesulfonate). A wide variety of these donors,
      including 2-deoxy sugar and sialyl donors, are easily prepared and shelf stable.
      The glycosidic coupling yields with alcohols are generally excellent; even direct
      coupling with the poorly nucleophilic amides gives satisfactory yields. Moreover,
      excellent alpha-selective glycosylation with a 2-deoxy sugar donor and beta
      selective sialylation have been realized. Application of the present
      glycosylation protocol in the efficient synthesis of a cyclic triterpene
      tetrasaccharide have further demonstrated the versatility and efficacy of this
      new method, in that a novel chemoselective glycosylation of the carboxylic acid
      and a new one-pot sequential glycosylation sequence have been implemented.

PMID- 20039349
TI  - Cobalt-mediated radical coupling (CMRC): an unusual route to midchain
      functionalized symmetrical macromolecules.
AB  - Cobalt-mediated radical coupling (CMRC) is a straightforward approach to the
      synthesis of symmetrical macromolecules that relies on the addition of 1,3-diene
      compounds onto polymer precursors preformed by cobalt-mediated radical
      polymerization (CMRP). Mechanistic features that make this process so efficient
      for radical polymer coupling are reported here. The mechanism was established on
      the basis of NMR spectroscopy and MALDI-MS analyses of the coupling product and
      corroborated by DFT calculations. A key feature of CMRC is the preferential
      insertion of two diene units in the middle of the chain of the coupling product
      mainly according to a trans-1,4-addition pathway. The large tolerance of CMRC
      towards the diene structure is demonstrated and the impact of this new coupling
      method on macromolecular engineering is discussed, especially for midchain
      functionalization of polymers. It is worth noting that the interest in CMRC goes
      beyond the field of polymer chemistry, since it constitutes a novel carbon-carbon
      bond formation method that could be applied to small organic molecules.

PMID- 20039350
TI  - Targeting bacterial membranes: NMR spectroscopy characterization of substrate
      recognition and binding requirements of D-arabinose-5-phosphate isomerase.
AB  - Lipopolysaccharide (LPS) is an essential component of the outer membrane of gram
      negative bacteria and consists of three elements: lipid A, the core
      oligosaccharide, and the O-antigen. The inner-core region is highly conserved and
      contains at least one residue of 3-deoxy-D-manno-octulosonate (Kdo). Arabinose-5
      phosphate isomerase (API) is an aldo-keto isomerase catalyzing the reversible
      isomerization of D-ribulose-5-phosphate (Ru5P) to D-arabinose-5-phosphate (A5P),
      the first step of Kdo biosynthesis. By exploiting saturation transfer difference
      (STD) NMR spectroscopy, the structural requirements necessary for API substrate
      recognition and binding were identified, with the aim of designing new API
      inhibitors. In addition, simple experimental conditions for the STD experiments
      to perform a fast, robust, and efficient screening of small libraries of
      potential API inhibitors, allowing the identification of new potential leads,
      were set up. Due to the essential role of API enzymes in LPS biosynthesis and
      gram-negative bacteria survival, by exploiting these data, a new generation of
      potent antibacterial drugs could be developed.

PMID- 20039351
TI  - A pH-responsive gate fabricated with nanochannels and nanoparticles.

PMID- 20039352
TI  - Dynamic kinetic asymmetric transformation (DYKAT) by combined amine- and
      transition-metal-catalyzed enantioselective cycloisomerization.
AB  - The first examples of one-pot highly chemo- and enantioselective dynamic kinetic
      asymmetric transformations (DYKATs) involving alpha,beta-unsaturated aldehydes
      and propargylated carbon acids are presented. These DYKATs, which proceed by a
      combination of catalytic iminium activation, enamine activation, and Pd(0)
      catalyzed enyne cycloisomerization, give access to functionalized cyclopentenes
      with up to 99 % ee and can be used for the generation of all-carbon quaternary
      stereocenters.

PMID- 20039353
TI  - An expeditious route to 1alpha,25-dihydroxyvitamin D(3) and its analogues by an
      aqueous tandem palladium-catalyzed a-ring closure and suzuki coupling to the C/D
      unit.

PMID- 20039354
TI  - The temperature-dependent hydrogen-bonding signature of lipids monitored in the
      far-infrared domain.
AB  - Phospholipids are studied by means of Fourier transform infrared (FTIR)
      spectroscopy in the mid- and far-infrared spectral ranges, thereby establishing
      the hydrogen-bonding continuum as a function of the temperature. The well-known
      mid-infrared spectrum of the phospholipid layer clearly shows a temperature
      dependent phase transition. In the far-infrared region (from 300 to 50 cm(-1)),
      an alternation of the interaction between the phospholipids and water molecules
      is found. The hydrogen-bonding network ensemble and bound water molecules can be
      monitored in this spectral region. The lipid structure is found to strongly
      influence the intermolecular hydrogen-bonding interplay. Thus, studies in the far
      infrared region provide significant information--at the molecular level--about
      the intermolecular hydrogen-bonding signature of self-assembled phospholipids.

PMID- 20039355
TI  - The relevance of the collaborative effect in determining the performances of
      photorefractive polymer materials.
AB  - A derivative of 2-methylindole, 3-[2-(4-nitrophenyl)ethenyl]-1-allyl-2
      methylindole, NPEMI-A, is studied for its photoconductivity and photorefractivity
      behaviour. Its blends with the organic polymer poly-(2,3-dimethyl-N-vinylindole),
      PVDMI, are also investigated. Due to the expected and devised mutual solubility
      of the two components of the blends, it is possible to carry out measurements
      with the weight percent of the chromophore NPEMI-A changing from zero to 100.
      Films were produced by a squeezing process between two ITO-covered glass sheets.
      No opacity phenomena, that are so common for many other organic blends due to the
      segregation of the dissolved chromophore, are observed. The photorefractive
      optical gain Gamma(2) is obtained as a function of the chromophore content.
      Differential scanning calorimetry measurements (DSC) are also carried out to
      obtain the whole change of the glass transition temperature T(g) as a function of
      the amount of chromophore contained in the blends. From the experimental trend of
      T(g) a meaningful quantitative estimate of the value of the electrostatic
      interactions acting in the studied blends, is obtained. The importance of the
      value of T(g), and of the electrostatic interactions, in determining the extent
      of the photorefractivity is clearly evident. The results are compared for NPEMI-A
      (Gamma(2) = 210 cm(-1)) and for NPEMI-E (Gamma(2) approximately = 2000 cm(-1))
      that has a N-2-ethylhexyl group instead of a N-allyl group. The Pockels and Kerr
      contributions and--for the first time--a "collaborative effect" of the
      photorefractivity of NPEMI-A are distinguished and quantitatively evaluated.

PMID- 20039356
TI  - The protonated guanine-cytosine base pair.
AB  - Protonated base pairs were recently implicated in the context of DNA proton
      transfer and charge migration. The effects of protonating different sites of the
      guanine-cytosine (GC) base pair are studied here by using the DZP++ B3LYP density
      functional method. Optimized structures for the protonated GC base pair are
      compared with those of parent GC and the neutral hydrogenated GC radical (GCH).
      Proton and hydrogen-atom additions significantly disturb the structure of the GC
      base pair. However, the structural perturbations arising from protonation are
      often less than those arising from hydrogenation of GC. Protonation of the GC
      base pair causes significant strengthening of the interstrand hydrogen bonds and
      a concomitant increase in the base dissociation energies. The adiabatic
      ionization potentials (AIPs), vertical ionization potentials (VIPs), and proton
      affinities (PAs) for the different protonation sites of the GC base pair are
      predicted. The N7 site of guanine is the preferred site for protonation of the GC
      base pair.

PMID- 20039357
TI  - Mesoscale surface patterning of a laterally-grafted rod amphiphile: rings and
      fibers.
AB  - An aromatic amphiphilic molecule based on branched oligo(ethylene oxide) was
      synthesized. Evaporation-driven ring formation and Langmuir-Blodgett films are
      investigated by utilizing this rigid-flexible block molecule. The size of the
      rings is strongly dependent on the solvent evaporation rate and the concentration
      of the molecule. In case of fast evaporation, volcano-like rings are formed by
      evaporating solution of high concentration. Perfectly symmetrical rings with
      diameters in the range of 2-6 microm are obtained by evaporating solution of low
      concentration. The formation mechanism of the ring is briefly discussed. The
      molecule at the air-water interface exhibits excellent amphiphilic properties.
      Upon transferring the monolayer onto solid substrates, AFM revealed the formation
      of fine and long, straight fibers. By combining the data obtained from the
      isotherms, AFM, water contact angle measurements, and UV/Vis and fluorescence
      spectra, the fibers are suggested to be formed by pi-pi stacking interaction of
      the aromatic rod segments as the oligo(ethylene oxide) branches are submerged in
      the water subphase upon compression. The fiber formation is associated with the
      transformation of the aromatic rod segments from the face-on conformation to the
      edge-on conformation.

PMID- 20039359
TI  - Discovery of indolone acetamides as novel SV2A ligands with improved potency
      toward seizure suppression.

PMID- 20039358
TI  - Identification, SAR studies, and X-ray co-crystallographic analysis of a novel
      furanopyrimidine aurora kinase A inhibitor.
AB  - Herein we reveal a simple method for the identification of novel Aurora kinase A
      inhibitors through substructure searching of an in-house compound library to
      select compounds for testing. A hydrazone fragment conferring Aurora kinase
      activity and heterocyclic rings most frequently reported in kinase inhibitors
      were used as substructure queries to filter the in-house compound library
      collection prior to testing. Five new series of Aurora kinase inhibitors were
      identified through this strategy, with IC(50) values ranging from approximately
      300 nM to approximately 15 microM, by testing only 133 compounds from a database
      of approximately 125,000 compounds. Structure-activity relationship studies and X
      ray co-crystallographic analysis of the most potent compound, a furanopyrimidine
      derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried
      out. The knowledge gained through these studies could help in the future design
      of potent Aurora kinase inhibitors.

PMID- 20039360
TI  - Palladium catalyzed direct 3-arylation of benzofurans using low catalyst
      loadings.
AB  - The palladium-catalyzed direct 3-arylation of benzofurans provides a cost
      effective and environmentally attractive route for the preparation of 3
      arylbenzofuran derivatives. The reactions were carried out using a wide variety
      of electronically and sterically diverse aryl or heteroaryl bromides with low
      catalyst loadings. In the presence of only 0.1-0.5 mol % catalyst, products in
      moderate to good yields were obtained. The aryl bromide reactants were able to
      tolerate a wide range of functionalities, such as acetyl, propionyl, formyl,
      ester, nitrile, trifluoromethyl, or fluoro groups. Higher yields were obtained
      using electron-deficient aryl bromides as reactants compared to using electron
      rich aryl bromides. Functionalized benzofuran derivatives, bearing formyl or
      hydroxymethyl on C2, were also successfully employed.

PMID- 20039363
TI  - From small ideas...

PMID- 20039365
TI  - A unique interplay between Rap1 and E-cadherin in the endocytic pathway regulates
      self-renewal of human embryonic stem cells.
AB  - Regulatory mechanisms pertaining to the self-renewal of stem cells remain
      incompletely understood. Here, we show that functional interactions between small
      GTPase Rap1 and the adhesion molecule E-cadherin uniquely regulate the self
      renewal of human embryonic stem cells (hESCs). Inhibition of Rap1 suppresses
      colony formation and self-renewal of hESCs, whereas overexpression of Rap1
      augments hESC clonogenicity. Rap1 does not directly influence the expression of
      the pluripotency genes Oct4 and Nanog. Instead, it affects the endocytic
      recycling pathway involved in the formation and maintenance of E-cadherin
      mediated cell-cell cohesion, which is essential for the colony formation and self
      renewal of hESCs. Conversely, distinct from epithelial cells, disruption of E
      cadherin mediated cell-cell adhesions induces lysosome delivery and degradation
      of Rap1. This in turn leads to a further downregulation of E-cadherin function
      and a subsequent reduction in hESC clonogenic capacity. These findings provide
      the first demonstration that the interplay between Rap1 and E-cadherin along the
      endocytic recycling pathway serves as a timely and efficient mechanism to
      regulate hESC self-renewal. Given the availability of specific activators for
      Rap1, this work provides a new perspective to enable better maintenance of human
      pluripotent stem cells.

PMID- 20039366
TI  - Boundary cap cells are highly competitive for CNS remyelination: fast migration
      and efficient differentiation in PNS and CNS myelin-forming cells.
AB  - During development, boundary cap cells (BC) and neural crest cell (NCC)
      derivatives generate Schwann cells (SC) of the spinal roots and a subpopulation
      of neurons and satellite cells in the dorsal root ganglia. Despite their stem
      like properties, their therapeutic potential in the diseased central nervous
      system (CNS) was never explored. The aim of this work was to explore BC
      therapeutic potential for CNS remyelination. We derived BC from Krox20(Cre) x
      R26R(Yfp) embryos at E12.5, when Krox20 is exclusively expressed by BC. Combining
      microdissection and cell fate mapping, we show that acutely isolated BC are a
      unique population closely related but distinct from NCC and SC precursors.
      Moreover, when grafted in the demyelinated spinal cord, BC progeny expands in the
      lesion through a combination of time-regulated processes including proliferation
      and differentiation. Furthermore, when grafted away from the lesion, BC progeny,
      in contrast to committed SC, show a high migratory potential mediated through
      enhanced interactions with astrocytes and white matter, and possibly with
      polysialylated neural cell adhesion molecule expression. In response to
      demyelinated axons of the CNS, BC progeny generates essentially myelin-forming
      SC. However, in contact with axons and astrocytes, some of them generate also
      myelin-forming oligodendrocytes. There are two primary outcomes of this study.
      First, the high motility of BC and their progeny, in addition to their capacity
      to remyelinate CNS axons, supports the view that BC are a reservoir of interest
      to promote CNS remyelination. Second, from a developmental point of view, BC
      behavior in the demyelinated CNS raises the question of the boundary between
      central and peripheral myelinating cells.

PMID- 20039367
TI  - High-throughput flow cytometry purification of transduced progenitors expressing
      defined levels of vascular endothelial growth factor induces controlled
      angiogenesis in vivo.
AB  - Delivery of therapeutic genes by genetically modified progenitors is a powerful
      tool for regenerative medicine. However, many proteins remain localized within or
      around the expressing cell, and heterogeneous expression levels can lead to
      reduced efficacy or increased toxicity. For example, the matrix-binding vascular
      endothelial growth factor (VEGF) can induce normal, stable, and functional
      angiogenesis or aberrant angioma growth depending on its level of expression in
      the microenvironment around each producing cell, and not on its total dose. To
      overcome this limitation, we developed a flow cytometry-based method to rapidly
      purify transduced cells expressing desired levels of a therapeutic transgene.
      Primary mouse myoblasts were transduced with a bicistronic retrovirus expressing
      VEGF linked to a nonfunctional, truncated form of the syngenic molecule CD8a. By
      using a clonal population uniformly expressing a known VEGF level as a reference,
      cells producing similar VEGF amounts were rapidly sorted from the primary
      population on the basis of their CD8a fluorescence intensity. A single round of
      sorting with a suitably designed gate yielded a purified population that induced
      robust, normal, and stable angiogenesis, and completely avoided angioma growth,
      which was instead always caused by the heterogeneous parent population. This
      clinically applicable high-throughput technique allowed the delivery of highly
      controlled VEGF levels in vivo, leading to significantly improved safety without
      compromising efficacy. Furthermore, when applied to other suitable progenitor
      populations, this technique could help overcome a significant obstacle in the
      development of safe and efficacious vascularization strategies in the fields of
      regenerative medicine and tissue engineering.

PMID- 20039368
TI  - Loss of LAP2 alpha delays satellite cell differentiation and affects postnatal
      fiber-type determination.
AB  - Lamina-associated polypeptide 2 alpha (LAP2 alpha) is a nucleoplasmic protein
      implicated in cell cycle regulation through its interaction with A-type lamins
      and the retinoblastoma protein. Mutations in lamin A/C and LAP2 alpha cause late
      onset striated muscle diseases, but the molecular mechanisms are poorly
      understood. To study the role of LAP2 alpha in skeletal muscle function and
      postnatal tissue homeostasis, we generated complete and muscle-specific LAP2
      alpha knockout mice. Whereas overall muscle morphology, function, and
      regeneration were not detectably affected, the myofiber-associated muscle stem
      cell pool was increased in complete LAP2 alpha knockout animals. At molecular
      level, the absence of LAP2 alpha preserved the stem cell-like phenotype of Lap2
      alpha(-/-) primary myoblasts and delayed their in vitro differentiation. In
      addition, loss of LAP2 alpha shifted the myofiber-type ratios of adult slow
      muscles toward fast fiber types. Conditional Cre-mediated late muscle-specific
      ablation of LAP2 alpha affected early stages of in vitro myoblast
      differentiation, and also fiber-type determination, but did not change myofiber
      associated stem cell numbers in vivo. Our data demonstrate multiple and distinct
      functions of LAP2 alpha in muscle stem cell maintenance, early phases of myogenic
      differentiation, and muscle remodeling.

PMID- 20039369
TI  - Novobiocin decreases SMYD3 expression and inhibits the migration of MDA-MB-231
      human breast cancer cells.
AB  - SET and MYND domain-containing protein 3 (SMYD3) is a histone methyltransferase
      that plays an important role in transcriptional regulation in human
      carcinogenesis, and heat-shock protein HSP90A has been shown to increase the
      activity of SMYD3. We previously reported that overexpression of SMYD3 stimulated
      the migration of cells. In this study, we further found that novobiocin, a HSP90
      inhibitor, could decrease the expression of SMYD3 and dose dependently inhibit
      the proliferation and migration of MDA-MB-231 human breast cancer cells. As a
      control, the short hairpin RNA (shRNA) targeting SMYD3 gene also showed similar
      effects with novobicin. This study is the first to show that novobiocin can
      inhibit the migration of breast cancer cells and such event may involve the
      downregulation of SMYD3. These findings might throw light on the development of
      novel therapeutic approaches to human cancers, and lend further understanding to
      the potential role of SMYD3 in human carcinogenesis.

PMID- 20039370
TI  - How I became a biochemist-from Moscow to Philadelphia, by way of Charlottesville:
      a story of one Wood/Whelan fellowship journey.

PMID- 20039372
TI  - Special series: Molecular chaperones in protein folding and disease.

PMID- 20039371
TI  - Search for the "ideal analgesic" in pain treatment by engineering the mu-opioid
      receptor.
AB  - The myriad of side effects that associate with morphine has been problematic in
      the clinical use to manage moderate to severe pain. It has been the holy grail of
      the pharmacologists to develop a compound, or treatment paradigm that could
      retain the analgesic effect of the drug as eliminating or reducing the side
      effects, mainly the tolerance and addiction development associates with chronic
      usage of the drug. In our earlier receptor structure/activities studies, we
      discovered an unique mutation of a conserved Ser in the fourth transmembrane
      domain of the opioid receptor that the alkaloid antagonist could activate the
      receptor. On the basis of this initial finding, we decide to explore the
      possibility of using virus to deliver the mutant mu-opioid receptor at the
      various sites of the nociceptive pathway and induce the antinociceptive responses
      with the systemic administration of opioid antagonists. In this article, we will
      summarize the progress of such approach and the probable advantages over the
      conventional approach of drug development in the treatment of chronic pain.

PMID- 20039374
TI  - Accurate control of oxygen level in cells during culture on silicone rubber
      membranes with application to stem cell differentiation.
AB  - Oxygen level in mammalian cell culture is often controlled by placing culture
      vessels in humidified incubators with a defined gas phase partial pressure of
      oxygen (pO(2gas)). Because the cells are consuming oxygen supplied by diffusion,
      a difference between pO(2gas) and that experienced by the cells (pO(2cell))
      arises, which is maximal when cells are cultured in vessels with little or no
      oxygen permeability. Here, we demonstrate theoretically that highly oxygen
      permeable silicone rubber membranes can be used to control pO(2cell) during
      culture of cells in monolayers and aggregates much more accurately and can
      achieve more rapid transient response following a disturbance than on polystyrene
      and fluorinated ethylene-propylene copolymer membranes. Cell attachment on
      silicone rubber was achieved by physical adsorption of fibronectin or Matrigel.
      We use these membranes for the differentiation of mouse embryonic stem cells to
      cardiomyocytes and compare the results with culture on polystyrene or on silicone
      rubber on top of polystyrene. The fraction of cells that are cardiomyocyte-like
      increases with decreasing pO(2) only when using oxygen-permeable silicone
      membrane-based dishs, which contract on silicone rubber but not polystyrene. The
      high permeability of silicone rubber results in pO(2cell) being equal to pO(2gas)
      at the tissue-membrane interface. This, together with geometric information from
      histological sections, facilitates development of a model from which the pO(2)
      distribution within the resulting aggregates is computed. Silicone rubber
      membranes have significant advantages over polystyrene in controlling pO(2cell),
      and these results suggest they are a valuable tool for investigating pO(2)
      effects in many applications, such as stem cell differentiation.

PMID- 20039375
TI  - Switchgrass leaching requirements for solid-state fermentation by Acidothermus
      cellulolyticus.
AB  - Growth of Acidothermus cellulolyticus in solid-state fermentation and its
      required growth conditions were investigated in this study. Extraction of
      switchgrass was required for growth. Under the experimental conditions,
      extraction ratio had the most significant effect on the growth of A.
      cellulolyticus. Heat treatment (in the form of autoclaving) of switchgrass did
      not have a significant effect on the growth rate; however, longer heat treatment
      times had a negative effect on the total growth. Moisture content adjustment had
      no effect on the release of inhibitors into extracts. Our results showed that
      leaching at a minimum 40:1 (gram water: gram dry biomass) removed inhibitory
      compound(s) from switchgrass. Upon extraction A. cellulolyticus colonized
      switchgrass in solid fermentation without exogenous addition of carbon and
      nitrogen sources. It is the first demonstration of growth of A. cellulolyticus in
      solid fermentation.

PMID- 20039376
TI  - pH measurement and a rational and practical pH control strategy for high
      throughput cell culture system.
AB  - The number of therapeutic proteins produced by cell culture in the pharmaceutical
      industry continues to increase. During the early stages of manufacturing process
      development, hundreds of clones and various cell culture conditions are evaluated
      to develop a robust process to identify and select cell lines with high
      productivity. It is highly desirable to establish a high throughput system to
      accelerate process development and reduce cost. Multiwell plates and shake flasks
      are widely used in the industry as the scale down model for large-scale
      bioreactors. However, one of the limitations of these two systems is the
      inability to measure and control pH in a high throughput manner. As pH is an
      important process parameter for cell culture, this could limit the applications
      of these scale down model vessels. An economical, rapid, and robust pH
      measurement method was developed at Eli Lilly and Company by employing SNARF-4F 5
      (-and 6)-carboxylic acid. The method demonstrated the ability to measure the pH
      values of cell culture samples in a high throughput manner. Based upon the
      chemical equilibrium of CO(2), HCO(3)(-), and the buffer system, i.e., HEPES, we
      established a mathematical model to regulate pH in multiwell plates and shake
      flasks. The model calculates the required %CO(2) from the incubator and the
      amount of sodium bicarbonate to be added to adjust pH to a preset value. The
      model was validated by experimental data, and pH was accurately regulated by this
      method. The feasibility of studying the pH effect on cell culture in 96-well
      plates and shake flasks was also demonstrated in this study. This work shed light
      on mini-bioreactor scale down model construction and paved the way for cell
      culture process development to improve productivity or product quality using high
      throughput systems.

PMID- 20039377
TI  - A multiparallel bioreactor for the cultivation of mammalian cells in a 3D-ceramic
      matrix.
AB  - For adherently growing cells, cultivation is limited by the provided growth
      surface. Excellent surface-to-volume ratios are found in highly porous matrices,
      which have to face the challenge of nutrient supply inside the matrices' caverns.
      Therefore, perfusion strategies are recommended which often have to deal with the
      need of developing an encompassing bioreactor periphery. We present a modular
      bioreactor system based on a porous ceramic matrix that enables the supply of
      cells with oxygen and nutrients by perfusion. The present version of the reactor
      system focuses on simple testing of various inoculation and operation modes.
      Moreover, it can be used to efficiently test different foam structures. Protocols
      are given to set-up the system together with handling procedures for long-time
      cultivation of a CHO cell line. Experimental results confirm vital growth of
      cells inside the matrices' caverns.

PMID- 20039378
TI  - Estimation of genotype relative risks from pedigree data by retrospective
      likelihoods.
AB  - Pedigrees collected for linkage studies are a valuable resource that could be
      used to estimate genetic relative risks (RRs) for genetic variants recently
      discovered in case-control genome wide association studies. To estimate RRs from
      highly ascertained pedigrees, a pedigree "retrospective likelihood" can be used,
      which adjusts for ascertainment by conditioning on the phenotypes of pedigree
      members. We explore a variety of approaches to compute the retrospective
      likelihood, and illustrate a Newton-Raphson method that is computationally
      efficient particularly for single nucleotide polymorphisms (SNPs) modeled as log
      additive effect of alleles on the RR. We also illustrate, by simulations, that a
      naive "composite likelihood" method that can lead to biased RR estimates, mainly
      by not conditioning on the ascertainment process-or as we propose-the disease
      status of all pedigree members. Applications of the retrospective likelihood to
      pedigrees collected for a prostate cancer linkage study and recently reported
      risk-SNPs illustrate the utility of our methods, with results showing that the
      RRs estimated from the highly ascertained pedigrees are consistent with odds
      ratios estimated in case-control studies. We also evaluate the potential impact
      of residual correlations of disease risk among family members due to shared
      unmeasured risk factors (genetic or environmental) by allowing for a random
      baseline risk parameter. When modeling only the affected family members in our
      data, there was little evidence for heterogeneity in baseline risks across
      families.

PMID- 20039379
TI  - A powerful approach to sub-phenotype analysis in population-based genetic
      association studies.
AB  - The ultimate goal of genome-wide association (GWA) studies is to identify genetic
      variants contributing effects to complex phenotypes in order to improve our
      understanding of the biological architecture underlying the trait. One approach
      to allow us to meet this challenge is to consider more refined sub-phenotypes of
      disease, defined by pattern of symptoms, for example, which may be
      physiologically distinct, and thus may have different underlying genetic causes.
      The disadvantage of sub-phenotype analysis is that large disease cohorts are sub
      divided into smaller case categories, thus reducing power to detect association.
      To address this issue, we have developed a novel test of association within a
      multinomial regression modeling framework, allowing for heterogeneity of genetic
      effects between sub-phenotypes. The modeling framework is extremely flexible, and
      can be generalized to any number of distinct sub-phenotypes. Simulations
      demonstrate the power of the multinomial regression-based analysis over existing
      methods when genetic effects differ between sub-phenotypes, with minimal loss of
      power when these effects are homogenous for the unified phenotype. Application of
      the multinomial regression analysis to a genome-wide association study of type 2
      diabetes, with cases categorized according to body mass index, highlights
      previously recognized differential mechanisms underlying obese and non-obese
      forms of the disease, and provides evidence of a potential novel association that
      warrants follow-up in independent replication cohorts.

PMID- 20039380
TI  - Case-only gene-environment interaction studies: when does association imply
      mechanistic interaction?
AB  - Case-only studies are often used to identify interactions between a genetic
      factor and an environmental factor under the assumption both factors are
      independent in the population. However, interpreting a statistical association
      between the genetic and the environmental factors among the cases, as evidence of
      a mechanistic gene-environment interaction, is not always warranted. Using a
      mechanistic approach based on the sufficient cause framework, we show association
      amongst cases can arise between the genetic and environmental factors when there
      is in fact no mechanistic gene-environment interaction. However, when it can be
      assumed the genetic and environmental factors themselves can never prevent the
      outcome, we show a positive association amongst cases implies a mechanistic gene
      environment interaction. Without this assumption that the effects of the two
      factors are never preventive, a multiplicative interaction greater than two is
      needed to conclude the presence of a mechanistic interaction. We furthermore show
      these tests for mechanistic interaction can be extended to scenarios in which the
      genetic and environmental factors are negatively associated in the population
      rather than independent.

PMID- 20039381
TI  - Techno-economic evaluation of a two-step biological process for hydrogen
      production.
AB  - An integrated biological process for the production of hydrogen based on
      thermophilic and photo-heterotrophic fermentation was evaluated from a technical
      and economic standpoint. Besides the two fermentation steps the process also
      includes pretreatment of the raw material (potato steam peels) and purification
      of hydrogen using amine absorption. The study aimed neither at determining the
      absolute cost of biohydrogen nor at an economic optimization of the production
      process, but rather at studying the effects of different parameters on the
      production costs of biohydrogen as a guideline for future improvements. The
      effect of the key parameters, hydrogen productivity and yield and substrate
      concentration in the two fermentations on the cost of the hydrogen produced was
      studied. The selection of the process conditions was based mainly on laboratory
      data. The process was simulated by use of the software Aspen Plus and the capital
      costs were estimated using the program Aspen Icarus Process Evaluator. The study
      shows that the photo-fermentation is the main contributor to the hydrogen
      production cost mainly because of the cost of plastic tubing, for the photo
      fermentors, which represents 40.5% of the hydrogen production cost. The costs of
      the capital investment and chemicals were also notable contributors to the
      hydrogen production cost. Major economic improvements could be achieved by
      increasing the productivity of the two fermentation steps on a medium-term to
      long-term scale.

PMID- 20039382
TI  - Lyophilised liposome-based formulations of alpha-tocopheryl succinate:
      preparation and physico-chemical characterisation.
AB  - alpha-Tocopheryl succinate (alpha-TOS) is a semisynthetic analogue of alpha
      tocopherol with selective toxicity to the cancer cells and anticancer activity in
      vivo. Yet, no suitable formulation of alpha-TOS for medical application has been
      reported. Various formulations, for example, solutions in organic solvents, oil
      emulsions and vesicules prepared by spontaneous vesiculation, polyethylene glycol
      conjugates and liposomes of various compositions have been tested. We developed
      and characterised a stable lyophilised liposome-based alpha-TOS formulation.
      alpha-TOS (15 mol%) was incorporated into large oligolamellar vesicles (OLVs)
      composed of soy phosphatidylcholine (SPC) by the method of lipid film hydration
      followed by extrusion through polycarbonate filters. Stabilised liposomal
      formulation was prepared by lyophilisation in the presence of sucrose (molar
      ratio lipid/sucrose, 1:5). The size distribution of the liposomes (130-140 nm,
      polydispersity index 0.14) as well as the stable lipid and alpha-TOS contents
      were preserved during storage in the lyophilised form at 2-8 degrees C for at
      least 6 months. The data indicate good physical and chemical stability of the
      lyophilised preparation of alpha-TOS liposomes that can be used in clinical
      medicine.

PMID- 20039383
TI  - On developing a process for conducting extractable-leachable assessment of
      components used for storage of biopharmaceuticals.
AB  - Extractables and leachables are product-related impurities that result from
      product contact with components such as gaskets, stoppers, storage bags,
      cartridges, and prefilled syringes that are used for processing, storage, and/or
      delivery of biopharmaceuticals. These impurities are a concern for patients due
      to potential effects on product quality and safety. It is possible that such an
      impurity could directly impact the patient or indirectly impact the patient by
      interacting with the protein therapeutics and forming protein adducts. Adducts
      and leachables may or may not be detected as product-related impurities in
      routine stability indicating assays depending on the rigor of the analytical
      program. The need for the development of a thorough and holistic extractable and
      leachable program based on risk assessment, review of existing literature, and
      consolidation of industry best practices is discussed. Standardizing component
      use within an organization enables streamlining of the extractable-leachable
      program. Our strategy for an extractable-leachable program is divided into
      different stages, each stage detailing the activities and the department within
      the organization that is responsible for execution of these activities. The roles
      and responsibilities of the key stakeholders are identified. The integration of
      analytical activities with health-based risk-assessment information into the
      design of an extractable-leachable program is highlighted.

PMID- 20039384
TI  - Detection of IgG aggregation by a high throughput method based on extrinsic
      fluorescence.
AB  - The utility of extrinsic fluorescence as a tool for high throughput detection of
      monoclonal antibody aggregates was explored. Several IgG molecules were thermally
      stressed and the high molecular weight species were fractionated using size
      exclusion chromatography (SEC). The isolated aggregates and monomers were studied
      by following the fluorescence of an extrinsic probe, SYPRO Orange. The dye
      displayed high sensitivity to structurally altered, aggregated IgG structures
      compared to the native form, which resulted in very low fluorescence in the
      presence of the dye. An example of the application is presented here to
      demonstrate the properties of this detection method. The fluorescence assay was
      shown to correlate with the SEC method in quantifying IgG aggregates. The
      fluorescent probe method appears to have potential to detect protein particles
      that could not be analyzed by SEC. This method may become a powerful high
      throughput tool to detect IgG aggregates in pharmaceutical solutions and to study
      other protein properties involving aggregation. It can also be used to study the
      kinetics of antibody particle formation, and perhaps allow identification of the
      species, which are the early building blocks of protein particles.

PMID- 20039385
TI  - Pharmacokinetic and pharmacodynamic evaluation of the lantibiotic MU1140.
AB  - Presented are the pharmacokinetics (PK), exposure-response relationship, and the
      PK/pharmacodynamic (PD) index predictive of maximum therapeutic efficacy for the
      lantibiotic MU1140. MU1140, at a dose of 12.5 or 25 mg/kg, was administered
      intravenously, to characterize its PK parameters in rat. The recently developed
      in vitro PD model of MU1140 activity was enhanced by incorporation of the PK of
      MU1140 in rat. The linked PK/PD model was used in a simulation study to determine
      the PK/PD index predictive of in vivo efficacy. MU1140 total plasma concentration
      time profiles declined biexponentially with elimination terminal half-life of 1.6
      +/- 0.1 h. Rapid injection of MU1140 was associated with a hypersensitivity
      reaction that can be blocked by premedication with diphenhydramine. The
      simulation study revealed that Staphylococcus aureus concentrations correlated
      with T > MIC making it the PK/PD index best predictive of efficacy. Collectively,
      these findings suggest that the best route of administration of MU1140 is slow
      infusion which will increase the time its concentration remains above the MIC,
      thus maximizing the therapeutic effect and minimizing the observed toxicity.

PMID- 20039386
TI  - Development of a transmucosal technique for erythromycin delivery to treat
      gastroparesis.
AB  - Gastroparesis is a serious condition that limits meal or medication emptying from
      the stomach, resulting in a variety of symptoms, altered nutrition, and
      inconsistent medication delivery. Our aim was to develop a transmucosal system to
      deliver erythromycin (EM), a gastric prokinetic agent, to bypass intestinal
      absorption. Humans and Sprague-Dawley rats were given EM by injection, gavage, or
      transmucosal gel with or without permeation enhancers. Pharmacokinetics were
      compared between subjects and across different delivery modalities. Drug
      concentrations in blood were measured using a bioassay. Design of Experiment
      techniques were used to optimize transmucosal antibiotic delivery in the Sprague
      Dawley Model. Finally, we examined the scale-up of transmucosal delivery to human
      patients. Transmucosal delivery of EM increased with addition of
      ursodeoxycholate. While EM release from gels with ursodeoxycholate was
      significant, it was less than by injection. Scale-up to a human model indicated
      that delivery of EM using this transmucosal delivery system is insufficient for
      clinical need. The transport of EM seems limited by its solubility in water and
      thickness of the epithelial cell layers. Providing successful transmucosal
      delivery of EM and similar molecules to humans will require more aggressive
      techniques to disrupt the cellular layer, or pro-drug strategies to increase
      lipid solubility.

PMID- 20039387
TI  - Evaluation of percutaneous absorption of naproxen from different liposomal
      formulations.
AB  - The present study concerns the percutaneous absorption of naproxen (NPX), as
      model anti-inflammatory drug, included in liposome formulations constituted of
      different lipids: stratum corneum lipids (SCL) and
      phosphatidylcholine/cholesterol (PC/CHOL). Liposome dispersions were produced
      using two different methods: reverse-phase evaporation (REV) and thin layer
      evaporation (TLE). Morphology and dimensions of the disperse phase were
      characterized by cryo-transmission electron microscopy (cryo-TEM) and photon
      correlation spectroscopy, respectively. X-ray diffraction was employed to
      determine the structural organization of the vesicles. In vitro diffusion was
      studied by Franz cell on liposome dispersions viscosized by carbomer. Tape
      stripping was performed to investigate in vivo the performance of differently
      composed liposomes as NPX delivery system. Cryo-TEM showed spherical vesicles and
      bigger irregular elongated nanoparticles for TLE SCL liposomes. REV resulted in
      spherical and elongated multilamellar vesicles. Also X-ray diffraction evidenced
      L alpha or L beta multilamellar vesicles for PC/CHOL and SCL liposome
      respectively. The in vitro study showed a lower NPX flux for SCL with respect to
      PC/CHOL liposome. Tape stripping corroborate the in vitro findings regarding SCL,
      suggesting that liposomes create a drug reservoir mixing with SC lipids, whilst
      PC/CHOL liposome promoted NPX permeation through the skin. Liposome lipid
      composition seems to affect NPX permeation through the skin.

PMID- 20039388
TI  - Evaluation of a rotary tablet press simulator as a tool for the characterization
      of compaction properties of pharmaceutical products.
AB  - The Stylcam 100R, a rotary press simulator, was designed to simulate speed
      profiles of rotary tablet presses. Such a simulator was qualified by numerous
      laboratories and, actually, its ability to be used for studying the behaviour of
      powders under pressure should be examined. Then, the purpose of this work was to
      investigate the performances of the Stylcam 100R for characterizing the
      compaction behaviour and the tabletting properties of pharmaceutical powders. The
      compressibility of three pharmaceutical excipients (microcrystalline cellulose,
      dicalcium phosphate dihydrate and alpha-lactose monohydrate) was studied. Four
      compression speeds were used on the compaction simulator. Force-displacement
      cycles were associated with two energy parameters, the specific total energy
      (Es(tot)) and the specific expansion energy (Es(exp)). The mean yield pressure
      was calculated from Heckel's plots obtained with the in-die method. The diametral
      tensile strength of compacts was measured in order to evaluate mechanical
      properties. To evaluate the accuracy of all these parameters, a comparative study
      was carried out on an eccentric instrumented press. The values of energy
      parameters and tensile strengths of tablets are close between the eccentric press
      and the compaction simulator, whatever the compression speed on the latter. The
      mean yield pressure values obtained using the two presses are different. Finally,
      the Stylcam 100R seems to be a good tool for characterising tabletting properties
      of powders, except for the Heckel's model probably due to an unadapted equation
      of deformation and a lack of accuracy of the displacement transducers. Future
      improvements should allow correcting these two points.

PMID- 20039389
TI  - Systematic investigation of the effect of lyophilizate collapse on
      pharmaceutically relevant proteins I: stability after freeze-drying.
AB  - The objective of this work was to investigate the effect of cake collapse during
      freeze-drying on the stability of protein lyophilizates containing a monoclonal
      IgG(1)-antibody or a second pharmaceutically relevant protein, referred to as
      PA01. In addition, L-lactic dehydrogenase was investigated because of its well
      documented sensitivity towards freeze-drying stresses. Collapse was induced by
      two different means. First, by varying the ratio of the crystalline bulking agent
      mannitol to the amorphous stabilizer sucrose, different extents of collapsed
      cakes were generated. Second, formulations were freeze-dried using an aggressive
      collapse-cycle and a conventional freeze-drying protocol and collapsed and
      noncollapsed cakes of identical formulation were produced. Lyophilizates were
      analyzed using a comprehensive set of analytical techniques to monitor protein
      stability in terms of formation of soluble and insoluble aggregates, the
      biological activity and the conformational stability. The stability of
      excipients, namely the glass transition temperature, crystallinity,
      reconstitution behavior, and the residual moisture content was analyzed as well.
      In addition, the extent of collapse was quantified using the decrease of the
      specific surface area (SSA). Collapsed cakes had comparable residual moisture
      levels to noncollapsed lyophilizates. Reconstitution times were not increased.
      Protein stability was not relevantly different between collapsed and noncollapsed
      cakes.

PMID- 20039390
TI  - Nanoparticle formation of organic compounds with retained biological activity.
AB  - Many pharmaceuticals are formulated as powders to aid drug delivery. A major
      problem is how to produce powders having high purity, controlled morphology, and
      retained bioactivity. We demonstrate the use of supercritical carbon dioxide as
      an antisolvent for meeting this need for two model drug systems, quercetin, a
      sparingly soluble antioxidant, and short interfering RNA (siRNA), which can
      silence genes. In both cases we achieve retention of bioactivity as well as a
      narrow particle size distribution in which the particles are free of impurities.

PMID- 20039391
TI  - The solubility-permeability interplay in using cyclodextrins as pharmaceutical
      solubilizers: mechanistic modeling and application to progesterone.
AB  - A quasi-equilibrium mass transport analysis has been developed to quantitatively
      explain the solubility-permeability interplay that exists when using
      cyclodextrins as pharmaceutical solubilizers. The model considers the effects of
      cyclodextrins on the membrane permeability (P(m)) as well as the unstirred water
      layer (UWL) permeability (P(aq)), to predict the overall effective permeability
      (P(eff)) dependence on cyclodextrin concentration (C(CD)). The analysis reveals
      that: (1) UWL permeability markedly increases with increasing C(CD) since the
      effective UWL thickness quickly decreases with increasing C(CD); (2) membrane
      permeability decreases with increasing C(CD), as a result of the decrease in the
      free fraction of drug; and (3) since P(aq) increases and P(m) decreases with
      increasing C(CD), the UWL is effectively eliminated and the overall P(eff) tends
      toward membrane control, that is, P(eff) approximately P(m) above a critical
      C(CD). Application of this transport model enabled excellent quantitative
      prediction of progesterone P(eff) as a function of HP beta CD concentrations in
      PAMPA assay, Caco-2 transepithelial studies, and in situ rat jejunal-perfusion
      model. This work demonstrates that when using cyclodextrins as pharmaceutical
      solubilizers, a trade-off exists between solubility increase and permeability
      decrease that must not be overlooked; the transport model presented here can aid
      in striking the appropriate solubility-permeability balance in order to achieve
      optimal overall absorption.

PMID- 20039392
TI  - Liquid-liquid miscibility gaps and hydrate formation in drug-water binary
      systems: pressure-temperature phase diagram of lidocaine and pressure-temperature
      composition phase diagram of the lidocaine-water system.
AB  - The pressure-temperature (P-T) melting curve of lidocaine was determined (dP/dT =
      3.56 MPa K(-1)), and the lidocaine-water system was investigated as a function of
      temperature and pressure. The lidocaine-water system exhibits a monotectic
      equilibrium at 321 K (ordinary pressure) whose temperature increases as the
      pressure increases until the two liquids become miscible. A hydrate, unstable at
      ordinary pressure, was shown to form, on increasing the pressure, from about 70
      MPa at low temperatures (200-300 K). The thermodynamic conditions of its
      stability were inferred from the location of the three-phase equilibria involving
      the hydrate in the lidocaine-water pressure-temperature-mole fraction (P-T-x)
      diagram.

PMID- 20039393
TI  - The combretastatin derivative (Cderiv), a vascular disrupting agent, enables
      polymeric nanomicelles to accumulate in microtumors.
AB  - A previous study found almost no leakage of polymeric nanomicelles from vessels
      in microtumors. If such vessels become leaky, sufficient nanomedicines may be
      delivered to microtumors and large tumors. To create leaky vessels, a
      combretastatin derivative (Cderiv), a vascular disrupting agent, was used. Via
      vital microscopy with fluorescein isothiocyanate (FITC)-labeled nanomicelles, the
      effect of Cderiv pretreatment on changes in micelle extravasation was
      investigated. Whether such treatment would prolong microtumor retention of
      micelles was also examined. FITC-albumin was used for comparison. The degree of
      extravasation from intact vessels in microtumors (rat sarcoma LY80) was extremely
      low and comparable to that from normal vessels. Cderiv pretreatment (1 or 3 days
      before administration of FITC-labeled compounds) markedly enhanced extravasation
      of such nanomicelles and albumin from vessels that survived treatment and had
      restored blood flow. A high concentration of extravasated macromolecules remained
      even 24 h later in tissue areas whose microcirculatory function had collapsed.
      Tumors receiving 10 Gy irradiation 3 days before the macromolecules evidenced
      gradual removal of extravasated macromolecules, which did not accumulate in those
      areas, despite extravasation from tumor vessels. Our results strongly suggest
      that pretreatment with Cderiv is quite effective for maintaining microtumor
      concentrations of nanomicelles and albumin associated with anticancer or
      diagnostic drugs.

PMID- 20039394
TI  - Evaluation of a dual-wavelength size exclusion HPLC method with improved
      sensitivity to detect protein aggregates and its use to better characterize
      degradation pathways of an IgG1 monoclonal antibody.
AB  - The evaluation of a dual wavelength size exclusion high performance liquid
      chromatography (DW-SE-HPLC) method with improved sensitivity to detect aggregates
      in a high concentration IgG1 monoclonal antibody formulation is presented. This
      technique utilizes ultraviolet detection at two different wavelengths to monitor
      the levels of monomer, aggregate, and fragments and was shown to have improved
      sensitivity for the detection aggregates and fragments compared to light
      scattering (LS) detection. After assay optimization including the use of column
      conditioning, the limit of quantitation for aggregates was determined to be 0.04%
      with essentially complete recovery of aggregates from the column (>99.5%). The DW
      SE-HPLC method was used to evaluate the level of protein aggregates generated by
      different environmental conditions such as exposure to elevated
      temperatures/acidic pH or intense light. The detection and characterization of
      protein aggregates by DW-SE-HPLC was compared with an orthogonal biophysical
      technique (sedimentation velocity analytical ultracentrifugation, SV-AUC). A good
      overall correlation was observed for levels of monomer, aggregates (dimer and
      multimers), and fragments as measured by the two analytical techniques (e.g.,
      6.0% vs. 5.3% and 14% vs. 11% for dimeric aggregates generated by elevated
      temperature/acidic pH and light exposure, respectively). The stability profile of
      a high concentration IgG1 monoclonal antibody formulation was investigated under
      stressed storage conditions (40 degrees C over 3 months) using the DW-SE-HPLC
      method including the loss of monomeric species with the concomitant accumulation
      of both aggregates and fragments. The nature and composition of the aggregates
      (primarily noncovalent dimers) and fragments (primarily loss of Fab from an
      intact IgG1) formed during storage were further characterized by a combination of
      LS measurements and mass spectroscopy analysis of deglycosylated IgG1 samples
      isolated by preparative SE-HPLC. The combination of DW-SE-HPLC, SV-AUC, LS, and
      mass spectroscopy results provided a detailed overall understanding the monomer,
      aggregate, fragment degradation pathway(s) for a high concentration IgG1
      monoclonal antibody formulation during storage.

PMID- 20039395
TI  - Expansion of circulating T cells resembling follicular helper T cells is a fixed
      phenotype that identifies a subset of severe systemic lupus erythematosus.
AB  - OBJECTIVE: In the sanroque mouse model of lupus, pathologic germinal centers
      (GCs) arise due to increased numbers of follicular helper T (Tfh) cells,
      resulting in high-affinity anti-double-stranded DNA antibodies that cause end
      organ inflammation, such as glomerulonephritis. The purpose of this study was to
      examine the hypothesis that this pathway could account for a subset of patients
      with systemic lupus erythematosus (SLE). METHODS: An expansion of Tfh cells is a
      causal, and therefore consistent, component of the sanroque mouse phenotype. We
      validated the enumeration of circulating T cells resembling Tfh cells as a
      biomarker of this expansion in sanroque mice, and we performed a comprehensive
      comparison of the surface phenotype of circulating and tonsillar Tfh cells in
      humans. This circulating biomarker was enumerated in SLE patients (n = 46),
      Sjogren's syndrome patients (n = 17), and healthy controls (n = 48) and was
      correlated with disease activity and end-organ involvement. RESULTS: In sanroque
      mice, circulating Tfh cells increased in proportion to their GC counterparts,
      making circulating Tfh cells a feasible human biomarker of this novel mechanism
      of breakdown in GC tolerance. In a subset of SLE patients (14 of 46), but in none
      of the controls, the levels of circulating Tfh cells (defined as circulating
      CXCR5+CD4+ cells with high expression of Tfh-associated molecules, such as
      inducible T cell costimulator or programmed death 1) were increased. This
      cellular phenotype did not vary with time, disease activity, or treatment, but it
      did correlate with the diversity and titers of autoantibodies and with the
      severity of end-organ involvement. CONCLUSION: These findings in SLE patients are
      consistent with the autoimmune mechanism in sanroque mice and identify Tfh
      effector molecules as possible therapeutic targets in a recognizable subset of
      patients with SLE.

PMID- 20039396
TI  - Humoral responses after influenza vaccination are severely reduced in patients
      with rheumatoid arthritis treated with rituximab.
AB  - OBJECTIVE: For patients with rheumatoid arthritis (RA), yearly influenza
      vaccination is recommended. However, its efficacy in patients treated with
      rituximab is unknown. The objectives of this study were to investigate the
      efficacy of influenza vaccination in RA patients treated with rituximab and to
      investigate the duration of the possible suppression of the humoral immune
      response following rituximab treatment. We also undertook to assess the safety of
      influenza vaccination and the effects of previous influenza vaccination. METHODS:
      Trivalent influenza subunit vaccine was administered to 23 RA patients who had
      received rituximab (4-8 weeks after rituximab for 11 patients [the early
      rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late
      rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy
      controls. Levels of antibodies against the 3 vaccine strains were measured before
      and 28 days after vaccination using hemagglutination inhibition assay. The
      Disease Activity Score in 28 joints (DAS28) was used to assess RA activity.
      RESULTS: Following vaccination, geometric mean titers (GMTs) of antiinfluenza
      antibodies significantly increased for all influenza strains in the MTX-treated
      group and in healthy controls, but for no strains in the rituximab-treated group.
      However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1
      strains was demonstrated, in the absence of a repopulation of CD19+ cells at the
      time of vaccination. Seroconversion and seroprotection occurred less often in the
      rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1
      strains, while seroprotection occurred less often in the rituximab-treated group
      than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated
      patients in the rituximab-treated group, previously vaccinated patients in the
      rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1
      strain. The DAS28 did not change after vaccination. CONCLUSION: Rituximab reduces
      humoral responses following influenza vaccination in RA patients, with a modestly
      restored response 6-10 months after rituximab administration. Previous influenza
      vaccination in rituximab-treated patients increases pre- and postvaccination
      titers. RA activity was not influenced.

PMID- 20039397
TI  - Immunization responses in rheumatoid arthritis patients treated with rituximab:
      results from a controlled clinical trial.
AB  - OBJECTIVE: To examine immunization responses in patients with rheumatoid
      arthritis (RA) treated with rituximab and to investigate the effects of rituximab
      induced CD20+ B cell depletion on immune responses to tetanus toxoid (T cell
      dependent antigen), pneumococcal polysaccharide (T cell-independent antigen), and
      keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity
      (DTH). METHODS: In a controlled trial, we enrolled 103 patients with active RA
      receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal
      polysaccharide, and KLH vaccines as well as a Candida albicans skin test were
      administered to 1 group of patients receiving rituximab plus MTX (called
      rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX
      alone for 12 weeks. The primary end point was the proportion of patients with a
      >or=4-fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and
      anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine
      administration. The DTH response to C albicans was measured 2-3 days following
      placement. RESULTS: Responses to tetanus toxoid vaccine (>or=4-fold rise) were
      similar in both groups (39.1% of rituximab-treated patients and 42.3% of patients
      treated with MTX alone). The ability to maintain a positive DTH response to the C
      albicans skin test was comparable in both groups (77.4% of rituximab-treated
      patients and 70% of patients treated with MTX alone), showing no effect of
      rituximab treatment. Rituximab-treated patients had decreased responses to
      pneumococcal polysaccharide vaccine (57% of patients had a 2-fold rise in titer
      in response to >or=1 serotype, compared with 82% of patients treated with MTX
      alone) and to KLH vaccine (47% of patients had detectable anti-KLH IgG, compared
      with 93% of patients treated with MTX alone). CONCLUSION: Recall responses to the
      T cell-dependent protein antigen tetanus toxoid as well as DTH responses were
      preserved in rituximab-treated RA patients 24 weeks after treatment. Responses to
      neoantigen (KLH) and T cell-independent responses to pneumococcal vaccine were
      decreased, but many patients were able to mount responses. These data suggest
      that polysaccharide and primary immunizations should be administered prior to
      rituximab infusions to maximize responses.

PMID- 20039398
TI  - Clinical images: Gastric antral vascular ectasia in systemic sclerosis.

PMID- 20039399
TI  - Somatic mutations and anti-mutated citrullinated vimentin antibodies in
      rheumatoid arthritis: comment on the editorial by Levesque et al.

PMID- 20039400
TI  - Thalidomide dramatically improves the symptoms of early-onset sarcoidosis/Blau
      syndrome: its possible action and mechanism.
AB  - OBJECTIVE: Early-onset sarcoidosis (EOS), which occurs in children younger than 5
      years of age, is associated with granulomatous lesions and a sporadic genetic
      mutation of the nucleotide-binding oligomerization domain 2 that causes
      constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable,
      progressive, and associated with profound complications. However, appropriate
      therapy is still under investigation. The aim of this study was to assess the
      efficacy of thalidomide in patients with severe EOS, based on etiology supporting
      an initial role of NF-kappaB in activation of this disease. METHODS: Thalidomide
      was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an
      initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. To
      elucidate the mechanism of the drug, peripheral blood monocytes were isolated
      from the patients and stimulated with cytokines (macrophage colony-stimulating
      factor, tumor necrosis factor alpha, and interleukin-4), and their ability to
      form multinucleated giant cells (MGCs) and osteoclasts was measured. RESULTS:
      Both patients showed dramatic improvement of their clinical symptoms (alleviation
      of fever and optic nerve papillitis, achievement of a response according to the
      American College of Rheumatology Pediatric 50 and Pediatric 70 criteria) and
      laboratory findings. Monocytes from patients with EOS had a greater ability to
      survive and induce MGCs and osteoclasts than those from healthy control subjects.
      The formation of MGCs and osteoclasts was inhibited by the presence of
      thalidomide. CONCLUSION: The ability of thalidomide to improve clinical symptoms
      and laboratory findings in patients with EOS indicates a central role for NF
      kappaB activity in this disorder. Inhibition of IKK might be a pharmacologic
      action by which thalidomide down-regulates NF-kappaB signaling. Thalidomide may
      be an effective medication in patients with severe complications of EOS,
      including ocular involvement.

PMID- 20039405
TI  - Direct comparison of treatment responses, remission rates, and drug adherence in
      patients with rheumatoid arthritis treated with adalimumab, etanercept, or
      infliximab: results from eight years of surveillance of clinical practice in the
      nationwide Danish DANBIO registry.
AB  - OBJECTIVE: To compare tumor necrosis factor alpha inhibitors directly regarding
      the rates of treatment response, remission, and the drug survival rate in
      patients with rheumatoid arthritis (RA), and to identify clinical prognostic
      factors for response. METHODS: The nationwide DANBIO registry collects data on
      rheumatology patients receiving routine care. For the present study, we included
      patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment
      was initiated (29% received adalimumab, 22% received etanercept, and 49% received
      infliximab). Baseline predictors of treatment response were identified. The odds
      ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for
      drug withdrawal were calculated, corrected for age, disease duration, the Disease
      Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and
      prednisolone, number of previous disease-modifying drugs, center, and functional
      status (Health Assessment Questionnaire score). RESULTS: Seventy percent
      improvement according to the American College of Rheumatology criteria (an ACR70
      response) was achieved in 19% of patients after 6 months. Older age, concomitant
      prednisolone treatment, and low functional status at baseline were negative
      predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response
      were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28
      2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for
      adalimumab versus etanercept. Similar predictors and ORs were observed for a good
      response according to the European League Against Rheumatism criteria, DAS28
      remission, and Clinical Disease Activity Index remission. At 48 months, the HRs
      for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40),
      1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab
      versus etanercept (95% CI 1.20-1.80). CONCLUSION: Older age, low functional
      status, and concomitant prednisolone treatment were negative predictors of a
      clinical response and remission. Infliximab had the lowest rates of treatment
      response, disease remission, and drug adherence, adalimumab had the highest rates
      of treatment response and disease remission, and etanercept had the longest drug
      survival rates. These findings were consistent after correction for confounders
      and sensitivity analyses and across outcome measures and followup times.

PMID- 20039404
TI  - Effect of long-term belimumab treatment on B cells in systemic lupus
      erythematosus: extension of a phase II, double-blind, placebo-controlled, dose
      ranging study.
AB  - OBJECTIVE: To understand the effects of long-term BLyS inhibition in human
      systemic lupus erythematosus (SLE). METHODS: Seventeen patients with SLE who were
      enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus
      standard of care therapy were studied. Phenotypic analysis of lymphocytes was
      performed using flow cytometry. Circulating antibody-secreting cells were
      enumerated using enzyme-linked immunospot assay. Serum was analyzed by enzyme
      linked immunosorbent assay using an antibody that recognizes products of the
      V(H)4-34 gene. Lymphocyte counts, Ig levels, and anti-double-stranded DNA
      antibody levels were available as part of the clinical trial analyses. RESULTS:
      Samples were collected on days 0, 84, 168, 365, and 532 and after day 730. The
      total number of B cells started to decrease from baseline between days 84 and
      168. This was due to a decrease in naive and transitional B cells. CD27+IgD+
      memory B cells and plasmablasts decreased only after 532 days, whereas CD27+IgD-
      memory B cells were not affected, and there were no changes in T cells. Serum IgM
      levels began to decline between days 84 and 168, but there were no changes in
      serum levels of IgG, IgG anti-DNA antibodies, or V(H)4-34 antibodies during the
      study. SLE patients had more IgM-, IgG-, and autoantibody-producing B cells than
      did normal controls on day 0. There was only a modest decrease in the frequency
      of total IgM-producing, but not IgG-producing, cells on days 365 and 532,
      consistent with the phenotypic and serologic data. CONCLUSION: Our data confirm
      the dependence of newly formed B cells on BLyS for survival in humans. In
      contrast, memory B cells and plasma cells are less susceptible to selective BLyS
      inhibition.

PMID- 20039406
TI  - Rheumatoid arthritis-specific autoantibodies to peptidyl arginine deiminase type
      4 inhibit citrullination of fibrinogen.
AB  - OBJECTIVE: Autoantibodies to citrullinated proteins are specific for rheumatoid
      arthritis (RA) and recognize epitopes centered by citrulline, a
      posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4
      (PAD-4), the enzyme that converts arginine into citrulline, is in itself a target
      for RA-specific autoantibodies. This study was undertaken to assess whether anti
      PAD-4 autoantibodies interfere with citrullination in vitro in patients with RA,
      and to identify peptide targets of anti-PAD-4 antibodies that can activate or
      inhibit citrullination. METHODS: To test whether autoantibodies to PAD-4
      influence citrullination, an in-house citrullination assay was developed using
      purified autoantibodies to PAD-4. To map B cell epitopes on PAD-4, 65 overlapping
      20-mer peptides encompassing the entire PAD-4 were analyzed for their reactivity
      in RA sera. RESULTS: Autoantibodies to PAD-4 inhibited PAD-4-mediated
      citrullination. Three linear peptides on PAD-4 were recognized almost uniquely by
      PAD-4 autoantibodies in the sera of patients with RA. One peptide was located in
      the N-terminal, calcium-binding domain of PAD-4, while 2 other peptides were
      located in the C-terminal, substrate-binding domain of PAD-4. CONCLUSION:
      Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4.
      Most anti-PAD-4-positive sera recognize peptides located both in the N-terminal
      domain (211-290) and the C-terminal domain (601-650) of PAD-4.

PMID- 20039407
TI  - Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis.
AB  - OBJECTIVE: Dkk-1 is an inhibitory molecule that regulates the Wnt pathway, which
      controls osteoblastogenesis. This study was undertaken to explore the potential
      role of Dkk-1 in ankylosing spondylitis (AS), a prototypical bone-forming
      disease. METHODS: Serum Dkk-1 levels were measured in 45 patients with AS, 45
      patients with rheumatoid arthritis (RA), 15 patients with psoriatic arthritis
      (PsA), and 50 healthy subjects by sandwich enzyme-linked immunosorbent assay
      (ELISA). A functional ELISA was used to assess the binding of Dkk-1 to its
      receptor (low-density lipoprotein receptor-related protein 6). Furthermore, we
      studied the effect of sera from patients with AS and healthy subjects on the
      activity of the Wnt pathway in the Jurkat T cell model, with and without a
      neutralizing anti-Dkk-1 monoclonal antibody, by Western immunoblotting. RESULTS:
      Serum Dkk-1 levels were significantly increased in patients with AS (mean +/- SEM
      2,730 +/- 135.1 pg/ml) as compared with normal subjects (P = 0.040), patients
      with RA (P = 0.020), and patients with PsA (P = 0.049). Patients with AS
      receiving anti-tumor necrosis factor alpha (anti-TNFalpha) treatment had
      significantly higher serum Dkk-1 levels than patients with AS not receiving such
      treatment (P = 0.007). Patients with AS studied serially prior to and following
      anti-TNFalpha administration exhibited a significant increase in serum Dkk-1
      levels (P = 0.020), in contrast to patients with RA, who exhibited a dramatic
      decrease (P < 0.001). Jurkat cells treated with serum from AS patients exhibited
      increased Wnt signaling compared with cells treated with control serum. In that
      system, Dkk-1 blockade significantly enhanced Wnt signaling in control serum
      treated, but not AS serum-treated, Jurkat T cells. CONCLUSION: Our findings
      indicate that in patients with AS, circulating bone formation-promoting factors
      functionally prevail. This can be at least partially attributed to decreased Dkk
      1-mediated inhibition.

PMID- 20039408
TI  - Lack of effect of a single injection of human C-reactive protein on murine lupus
      or nephrotoxic nephritis.
AB  - OBJECTIVE: It has been reported that a single dose of human C-reactive protein
      (CRP) can prevent and reverse the renal damage in murine models of spontaneous
      lupus, as well as the rapid-onset immune complex disease induced in the
      accelerated nephrotoxic nephritis (ANTN) model. This study was undertaken to
      attempt to replicate these observations using a highly purified and fully
      characterized human CRP preparation. METHODS: (NZB x NZW)F(1) (NZB/NZW) mice were
      treated with a single 200-microg subcutaneous injection of CRP or control
      reagents either before disease onset at 4 months of age or when high-grade
      proteinuria was present at 7 months of age. Mice were monitored at least monthly
      for proteinuria and autoantibody levels. ANTN was induced by preimmunizing
      C57BL/6 mice with sheep IgG, followed 5 days later by injection of sheep anti
      mouse glomerular basement membrane antibody and CRP or control reagents. Renal
      disease was assessed by regular urinalysis and histologic evaluation. RESULTS:
      CRP treatment of NZB/NZW mice, either early or late in the disease, had no effect
      on proteinuria, autoantibody titers, or survival. CRP administration did not
      reduce renal injury or alter disease in the ANTN model. Human serum amyloid P
      component, a pentraxin protein that is very closely related to CRP, similarly had
      no effect. CONCLUSION: Our completely negative observations do not confirm that
      human CRP has reproducible antiinflammatory or immunomodulatory effects in these
      murine models, nor do they support the suggestion that CRP might be useful for
      therapy of lupus or immune complex-mediated nephritis.

PMID- 20039410
TI  - The tidemark of cartilage as a potential target of the rheumatoid response:
      comment on the editorial by Suber and Rosen.

PMID- 20039409
TI  - Anti-neuropilin-1 peptide inhibition of synoviocyte survival, angiogenesis, and
      experimental arthritis.
AB  - OBJECTIVE: To delineate the role of neuropilin-1 (NP-1), a vascular endothelial
      growth factor receptor (VEGFR), in rheumatoid inflammation and to determine
      whether blockade of NP-1 could suppress synoviocyte survival and angiogenesis.
      METHODS: VEGF(111-165) peptide, which encompasses the NP-1 binding domain of
      VEGF(165), was generated by cleaving VEGF(165) with plasmin. The effect of this
      peptide on the interaction between VEGF(165) and its receptor was determined by
      (125)I-VEGFR binding assay. Assays to determine synoviocyte apoptosis, adhesion,
      and migration were performed in the presence of VEGF(165) and/or the peptide.
      VEGF(165)-induced angiogenesis was assessed by measuring the proliferation, tube
      formation, and wounding migration of endothelial cells (ECs). Mice were immunized
      with type II collagen to induce experimental arthritis. RESULTS: VEGF(111-165)
      peptide specifically inhibited the binding of (125)I-VEGF(165) to NP-1 on
      rheumatoid synoviocytes and ECs. The peptide eliminated the VEGF(165)-mediated
      increase in synoviocyte survival and activation of p-ERK and Bcl-2. The peptide
      also completely inhibited a VEGF(165)-induced increase in synoviocyte adhesion
      and migration. In addition, the anti-NP-1 peptide blocked VEGF(165)-stimulated
      proliferation, capillary tube formation, and wounding migration of ECs in vitro.
      VEGF(165)-induced neovascularization in a Matrigel plug in mice was also blocked
      by treatment with the peptide. Finally, subcutaneous injection of anti-NP-1
      peptide suppressed arthritis severity and autoantibody formation in mice with
      experimental arthritis and inhibited synoviocyte hyperplasia and angiogenesis in
      arthritic joints. CONCLUSION: Anti-NP-1 peptide suppressed VEGF(165)-induced
      increases in synoviocyte survival and angiogenesis, and thereby blocked
      experimental arthritis. Our findings suggest that anti-NP-1 peptide could be
      useful in alleviating chronic arthritis.

PMID- 20039411
TI  - Identification of citrullinated vimentin peptides as T cell epitopes in HLA-DR4
      positive patients with rheumatoid arthritis.
AB  - OBJECTIVE: Antibodies directed against citrullinated proteins (ACPAs) are highly
      specific for rheumatoid arthritis (RA). The production of ACPAs is most likely
      dependent on the presence of T cells, since ACPAs undergo isotype switching and
      are associated with the shared epitope (SE)-containing HLA-DRB1 alleles. Vimentin
      is a likely candidate protein for T cell recognition, since >90% of patients
      positive for ACPAs that are reactive with (peptides derived from) citrullinated
      vimentin carry SE-containing HLA-DRB1 alleles. The aim of this study was to
      identify citrullinated vimentin peptides that are presented to HLA-DRB1*0401
      restricted T cells. METHODS: HLA-DR4-transgenic mice were immunized with all
      possible citrulline-containing peptides derived from vimentin, and T cell
      reactivity was analyzed. Peptides recognized in a citrulline-specific manner by T
      cells were selected and analyzed for their ability to be processed from the
      entire vimentin protein. A first inventory of the selected epitopes recognized by
      T cells was performed using peripheral blood mononuclear cells (PBMCs) from
      ACPA+, HLA-DR4+ patients with RA. RESULTS: A citrulline-specific response was
      observed for 2 of the peptides analyzed in DR4-transgenic mice. These peptides
      were found to be naturally processed from the vimentin protein, since
      citrullinated vimentin was recognized by peptide-specific T cells. T cell
      reactivity against these peptides was also observed in cultures of PBMCs from RA
      patients. CONCLUSION: This study identifies, for the first time, 2 naturally
      processed peptides from vimentin that are recognized by HLA-DRB1*0401-restricted
      T cells in a citrulline-specific manner. These peptides can be recognized by T
      cells in ACPA+, HLA-DR4+ patients with RA, as shown in a first inventory.

PMID- 20039412
TI  - Involvement of MAPKs and NF-kappaB in tumor necrosis factor alpha-induced
      vascular cell adhesion molecule 1 expression in human rheumatoid arthritis
      synovial fibroblasts.
AB  - OBJECTIVE: To investigate the roles of MAPKs and NF-kappaB in tumor necrosis
      factor alpha (TNFalpha)-induced expression of vascular cell adhesion molecule 1
      (VCAM-1) in human rheumatoid arthritis synovial fibroblasts (RASFs). METHODS:
      Human RASFs were isolated from synovial tissue obtained from patients with RA who
      underwent knee or hip surgery. The involvement of MAPKs and NF-kappaB in TNFalpha
      induced VCAM-1 expression was investigated using pharmacologic inhibitors and
      transfection with short hairpin RNA (shRNA) and measured using Western blot,
      reverse transcriptase-polymerase chain reaction, and gene promoter assay. NF
      kappaB translocation was determined by Western blot and immunofluorescence
      staining. The functional activity of VCAM-1 was evaluated by lymphocyte adhesion
      assay. RESULTS: TNFalpha-induced VCAM-1 expression, phosphorylation of p42/p44
      MAPK, p38 MAPK, and JNK, and translocation of NF-kappaB were attenuated by the
      inhibitors of MEK-1/2 (U0126), p38 (SB202190), JNK (SP600125), and NF-kappaB
      (helenalin) or by transfection with their respective shRNA. TNFalpha-stimulated
      translocation of NF-kappaB into the nucleus and NF-kappaB promoter activity were
      blocked by Bay11-7082, but not by U0126, SB202190, or SP600125. VCAM-1 promoter
      activity was enhanced by TNFalpha in RASFs transfected with VCAM-1-Luc, and this
      promoter activity was inhibited by Bay11-7082, U0126, SB202190, and SP600125.
      Moreover, up-regulation of VCAM-1 increased the adhesion of lymphocytes to the
      RASF monolayer, and this adhesion was attenuated by pretreatment with helenalin,
      U0126, SP600125, or SB202190 prior to exposure to TNFalpha or by anti-VCAM-1
      antibody before the addition of lymphocytes. CONCLUSION: In RASFs, TNFalpha
      induced VCAM-1 expression is mediated through activation of the p42/p44 MAPK, p38
      MAPK, JNK, and NF-kappaB pathways. These results provide new insights into the
      mechanisms underlying cytokine-initiated joint inflammation in RA and may inspire
      new targeted therapeutic approaches.

PMID- 20039414
TI  - Human nucleus pulposus cell cultures and disc degeneration grading systems:
      comment on the article by Le Maitre et al.

PMID- 20039413
TI  - Efficacy and safety of rituximab in moderately-to-severely active systemic lupus
      erythematosus: the randomized, double-blind, phase II/III systemic lupus
      erythematosus evaluation of rituximab trial.
AB  - OBJECTIVE: B cells are likely to contribute to the pathogenesis of systemic lupus
      erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory
      Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and
      safety of rituximab versus placebo in patients with moderately-to-severely active
      extrarenal SLE. METHODS: Patients entered with >or=1 British Isles Lupus
      Assessment Group (BILAG) A score or >or=2 BILAG B scores despite background
      immunosuppressant therapy, which was continued during the trial. Prednisone was
      added and subsequently tapered. Patients were randomized at a ratio of 2:1 to
      receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. RESULTS: In
      the intent-to-treat analysis of 257 patients, background treatment was evenly
      distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty
      three percent of the patients had >or=1 BILAG A score at entry, and 57% of the
      patients were categorized as being steroid dependent. No differences were
      observed between placebo and rituximab in the primary and secondary efficacy end
      points, including the BILAG-defined response, in terms of both area under the
      curve and landmark analyses. A beneficial effect of rituximab on the primary end
      point was observed in the African American and Hispanic subgroups. Safety and
      tolerability were similar in patients receiving placebo and those receiving
      rituximab. CONCLUSION: The EXPLORER trial enrolled patients with moderately-to
      severely active SLE and used aggressive background treatment and sensitive
      cutoffs for nonresponse. No differences were noted between placebo and rituximab
      in the primary and secondary end points. Further evaluation of patient subsets,
      biomarkers, and exploratory outcome models may improve the design of future SLE
      clinical trials.

PMID- 20039415
TI  - Reply to letter by Priori et al commenting on whether Behcet's syndrome patients
      with acne and arthritis comprise a true subset.

PMID- 20039416
TI  - Incidence and prevention of bladder toxicity from cyclophosphamide in the
      treatment of rheumatic diseases: a data-driven review.

PMID- 20039417
TI  - Evaluation of the efficacy and safety of terguride in patients with fibromyalgia
      syndrome: results of a twelve-week, multicenter, randomized, double-blind,
      placebo-controlled, parallel-group study.
AB  - OBJECTIVE: To assess the efficacy and safety of terguride, a partial dopamine
      agonist, in patients with fibromyalgia syndrome (FMS). METHODS: In a 12-week,
      multicenter, double-blind, placebo-controlled, parallel-group study, 99 patients
      were randomized at a ratio of 2 to 1 to receive terguride or placebo. Over 21
      days, the dosage was titrated to a maximum daily dose of 3 mg of terguride or
      placebo, and this fixed dosage was continued over 9 weeks. The primary efficacy
      variable was the intensity of pain (100-mm visual analog scale). Secondary
      efficacy variables included the Fibromyalgia Impact Questionnaire (FIQ) score,
      the tender point score (TPS), and the Hamilton Depression Scale (HDS) score.
      During the study, patients were evaluated for the presence of cervical spine
      stenosis by magnetic resonance imaging (MRI). RESULTS: No significant differences
      in the change in pain intensity, FIQ score, TPS, or HDS score between baseline
      and 12 weeks were observed in the terguride group as compared with the placebo
      group. Cervical spine stenosis was detected in 22% of the patients. Only patients
      with cervical spine stenosis responded to terguride treatment. FIQ scores
      improved significantly (per-protocol analysis), and pain intensity, the TPS
      score, and the HDS score showed a trend toward improvement in the terguride group
      as compared with the placebo group. Terguride treatment was safe. Only those
      adverse events already known to be side effects of terguride were observed.
      Premature termination of the study in patients receiving terguride (26%) occurred
      predominantly during up-titration and in the absence of comedication for
      treatment of nausea. CONCLUSION: Terguride treatment did not improve pain, the
      FIQ score, the TPS, or the HDS score in the total study population. However, a
      subgroup of patients with cervical spine stenosis seemed to benefit from
      terguride treatment.

PMID- 20039418
TI  - Inhibition of NF-kappaB signaling by fasudil as a potential therapeutic strategy
      for rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is the most common systemic autoimmune
      disease and is characterized mainly by symmetric polyarticular joint disorders.
      The pathologic processes are mediated by a number of cytokines, chemokines, cell
      adhesion molecules, and matrix metalloproteinases. The expression of most of
      these molecules is controlled at the transcriptional level. In addition,
      activation of NF-kappaB is involved in RA pathogenesis. This study was performed
      to explore the role of a novel serine/threonine kinase inhibitor, fasudil, in the
      control of the NF-kappaB activation pathway and to investigate the therapeutic
      effects of fasudil on arthritis development in a rat model of RA. METHODS:
      Fibroblast-like synoviocytes (FLS) from RA patients and human endothelial cells
      (ECs) were established and maintained. To study the role of fasudil on cytokine
      expression, various cytokines expressed in the RA FLS and human ECs were measured
      by enzyme-linked immunosorbent assay following stimulation of the cells with
      interleukin-1beta (IL-1beta) in the presence of various concentrations of
      fasudil. The role of fasudil on NF-kappaB activation was studied using a reporter
      gene assay, Western blotting of IkappaBalpha, immunofluorescence analysis of the
      p65 subunit of NF-kappaB, and electrophoretic mobility shift assay. The in vivo
      effects of fasudil on arthritis were studied in a rat adjuvant-induced arthritis
      (AIA) model. RESULTS: Fasudil inhibited cytokine expression in RA FLS and human
      ECs and also inhibited the activation of ECs, in a dose-dependent manner. Fasudil
      inhibited IL-1beta-induced activation of NF-kappaB independent of the inhibition
      of IkappaBalpha degradation and nuclear translocation of NF-kappaB, and inhibited
      IL-1beta-induced DNA binding of NF-kappaB. Finally, in vivo, fasudil ameliorated
      arthritis in rats with AIA, without any adverse effects. CONCLUSION:
      Serine/threonine kinase inhibitor fasudil inhibits the development of arthritis
      in a rat model of RA, and also inhibits the NF-kappaB signaling required for
      binding of NF-kappaB to specific DNA sequences through, for example, the
      phosphorylation of p65, suggesting that a specific target of fasudil might be a
      novel NF-kappaB kinase. Thus, fasudil serves as a novel strategy for the
      treatment of RA.

PMID- 20039419
TI  - Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in
      patients with rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is considered to be a prototypical
      autoimmune disease. However, the autoantigens that play an important role in the
      development of RA remain unclear. The aim of this study was to investigate
      whether T cells specific for citrullinated epitopes from self proteins are
      present in patients with RA. METHODS: Peripheral blood mononuclear cells (PBMCs)
      from 28 RA patients and 18 healthy controls were stimulated with citrullinated or
      noncitrullinated aggrecan peptide Agg(84-103), and proliferative and cytokine
      responses were assessed using (3)H-thymidine incorporation assay, enzyme-linked
      immunosorbent assay, and intracellular cytokine analysis. RESULTS: A
      proliferative response to the citrullinated aggrecan peptide was detected in >60%
      of RA patients but not in healthy controls. Furthermore, citrullinated aggrecan
      peptide-stimulated PBMCs from RA patients produced high levels of the
      proinflammatory cytokine interleukin-17 (IL-17), accompanied by an induction of
      IL-17+CD4+ T cells. In contrast, PBMCs from RA patients and healthy controls
      exhibited no response to stimulation with the noncitrullinated aggrecan peptide.
      CONCLUSION: Proinflammatory T cell responses to stimulation with a citrullinated
      arthritogenic aggrecan peptide were detected in RA patients but not in healthy
      individuals, suggesting a role for these autoantigen-specific T cells in the
      pathogenesis of RA. Our results suggest that the lack of response to the
      noncitrullinated analog peptide not only implicates the citrulline residue in T
      cell recognition but also highlights the potential value of citrullinated
      aggrecan peptide-specific responses as biomarkers of RA. To our knowledge, this
      is the first study to demonstrate the presence of citrullinated antigen-specific
      T cells in human RA.

PMID- 20039420
TI  - Muscle resident macrophages control the immune cell reaction in a mouse model of
      notexin-induced myoinjury.
AB  - OBJECTIVE: Skeletal muscle may be the site of a variety of poorly understood
      immune reactions, particularly after myofiber injury, which is typically observed
      in inflammatory myopathies. This study was undertaken to explore both the cell
      dynamics and functions of resident macrophages and dendritic cells (DCs) in
      damaged muscle, using a mouse model of notexin-induced myoinjury to study innate
      immune cell reactions. METHODS: The myeloid cell reaction to notexin-induced
      myoinjury was analyzed by microscopy and flow cytometry. Bone marrow (BM)
      transplantation studies were used to discriminate resident from exudate
      monocyte/macrophages. Functional tests included cytokine screening and an
      alloantigenic mixed leukocyte reaction to assess the antigen-presenting cell
      (APC) function. Selective resident macrophage depletion was obtained by injection
      of diphtheria toxin (DT) into CD11b-DT receptor-transgenic mice transplanted with
      DT-insensitive BM. RESULTS: The connective tissue surrounding mouse
      muscle/fascicle tissue (the epimysium/perimysium) after deep muscle injury
      displayed a resident macrophage population of CD11b+F4/80+CD11c-Ly-6C-CX3CR1-
      cells, which concentrated first in the epimysium. These resident macrophages were
      being used by leukocytes as a centripetal migration pathway, and were found to
      selectively release 2 chemokines, cytokine-induced neutrophil chemoattractant and
      monocyte chemoattractant protein 1, and to crucially contribute to massive
      recruitment of neutrophils and monocytes from the blood. Early epimysial
      inflammation consisted of a predominance of Ly-6C(high)CX3CR1(low)CD11c- cells
      that were progressively substituted by Ly-6C(low)CX3CR1(high) cells displaying an
      intermediate, rather than high, level of CD11c expression. These
      CD11c(intermediate) cells were derived from circulating CCR2+ monocytes,
      functionally behaved as immature APCs in the absence of alloantigenic challenge,
      and migrated to draining lymph nodes while acquiring the phenotype of mature DCs
      (CD11c+Ia+CD80+ cells, corresponding to an inflammatory DC phenotype).
      CONCLUSION: The results in this mouse model show that resident macrophages in the
      muscle epimysium/perimysium orchestrate the innate immune response to myoinjury,
      which is linked to adaptive immunity through the formation of inflammatory DCs.

PMID- 20039421
TI  - 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22
      expression by memory T cells from patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To examine the immunologic mechanism by which 1,25-dihydroxyvitamin
      D(3) (1,25[OH](2)D(3)) may prevent corticosteroid-induced osteoporosis in
      patients with early rheumatoid arthritis (RA), with a focus on T cell biology.
      METHODS: Peripheral blood mononuclear cells (PBMCs) and CD4+CD45RO+ (memory) and
      CD4+CD45RO- (non-memory) T cells separated by fluorescence-activated cell sorting
      (FACS) from treatment-naive patients with early RA were stimulated with anti
      CD3/anti-CD28 in the absence or presence of various concentrations of
      1,25(OH)(2)D(3), dexamethasone (DEX), and 1,25(OH)(2)D(3) and DEX combined.
      Levels of T cell cytokines were determined by enzyme-linked immunosorbent assay
      and flow cytometry. RESULTS: The presence of 1,25(OH)(2)D(3) reduced interleukin
      17A (IL-17A) and interferon-gamma levels and increased IL-4 levels in stimulated
      PBMCs from treatment-naive patients with early RA. In addition, 1,25(OH)(2)D(3)
      had favorable effects on tumor necrosis factor alpha (TNFalpha):IL-4 and IL
      17A:IL-4 ratios and prevented the unfavorable effects of DEX on these ratios.
      Enhanced percentages of IL-17A- and IL-22-expressing CD4+ T cells and IL-17A
      expressing memory T cells were observed in PBMCs from treatment-naive patients
      with early RA as compared with healthy controls. Of note, we found no difference
      in the percentage of CD45RO+ and CD45RO- cells between these 2 groups.
      Interestingly, 1,25(OH)(2)D(3), in contrast to DEX, directly modulated human Th17
      polarization, accompanied by suppression of IL-17A, IL-17F, TNFalpha, and IL-22
      production by memory T cells sorted by FACS from patients with early RA.
      CONCLUSION: These data indicate that 1,25(OH)(2)D(3) may contribute its bone
      sparing effects in RA patients taking corticosteroids by the modulation of Th17
      polarization, inhibition of Th17 cytokines, and stimulation of IL-4.

PMID- 20039422
TI  - Good and bad memories following rituximab therapy.

PMID- 20039423
TI  - Emerging from the shadows: follicular helper T cells in autoimmunity.

PMID- 20039424
TI  - Rho kinase-dependent activation of SOX9 in chondrocytes.
AB  - OBJECTIVE: The transcription factor SOX9 directly regulates the expression of the
      major proteoglycans and collagens comprising the cartilage extracellular matrix.
      The DNA binding activity and cellular localization of SOX9 is controlled through
      posttranslational modifications, including phosphorylation. The activity of Rho
      kinase (ROCK) has profound effects on the actin cytoskeleton, and these effects
      are instrumental in determining the phenotype and differentiation of
      chondrocytes. However, the mechanisms linking ROCK to altered chondrocyte gene
      expression remain unknown. The purpose of the present study was to test for a
      direct interaction between ROCK and SOX9. METHODS: Human SW1353 chondrosarcoma
      cells were transfected with constructs coding for RhoA, ROCK, Lim kinase, and
      SOX9. The interaction between ROCK and SOX9 was tested on purified proteins, and
      was verified within a cellular context using induced overexpression and
      activation of the Rho pathway. The effects of SOX9 transcriptional activation
      were quantified with a luciferase reporter plasmid containing SOX9 binding sites
      from the COL2A1 enhancer element. RESULTS: SOX9 was found to contain a consensus
      phosphorylation site for ROCK. In vitro, ROCK directly phosphorylated SOX9 at
      Ser(181), and the overexpression of ROCK or the activation of the RhoA pathway in
      SW1353 chondrosarcoma cells increased SOX9(Ser181) phosphorylation. ROCK caused a
      dose-dependent increase in the transcription of a SOX9-luciferase reporter
      construct, and increased phosphorylation and nuclear accumulation of SOX9 protein
      in response to transforming growth factor beta treatment and mechanical
      compression. CONCLUSION: These results demonstrate a new interaction that
      directly links ROCK to increased cartilage matrix production via activation of
      SOX9 in response to mechanical and growth factor stimulation.

PMID- 20039426
TI  - Statin treatment of rheumatoid arthritis: comment on the editorial by Ridker and
      Solomon.

PMID- 20039425
TI  - Rapid and sustained improvement in bone and cartilage turnover markers with the
      anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid
      arthritis patients with an inadequate response to methotrexate: results from a
      substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab
      in inadequate responders to methotrexate alone.
AB  - OBJECTIVE: To investigate the effects of tocilizumab (TCZ) added to a stable
      dosage of methotrexate (MTX) on biochemical markers of bone and cartilage
      metabolism in patients in the multicenter double-blind, placebo-controlled OPTION
      (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study who have
      moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to MTX.
      METHODS: Included in this study were 416 of the 623 patients with active RA
      enrolled in the OPTION study. Patients were randomized to receive TCZ (4 mg/kg or
      8 mg/kg) or placebo intravenously every 4 weeks, with MTX continued at the stable
      prestudy doses (10-25 mg for 20 weeks, with a final followup at week 24). Serum
      biochemical markers of bone formation (osteocalcin, N-terminal propeptide of type
      I collagen [PINP]), bone resorption (C-terminal crosslinking telopeptide of type
      I collagen [CTX-I] and C-terminal crosslinking telopeptide of type I collagen
      generated by matrix metalloproteinases [ICTP]), cartilage metabolism (N-terminal
      propeptide of type IIA collagen [PIIANP]), collagen helical peptide [HELIX-II]),
      and matrix metalloproteinase 3 (MMP-3) were measured at baseline and at weeks 4,
      16, and 24. RESULTS: TCZ induced marked dose-dependent reductions in PIIANP,
      HELIX-II, and MMP-3 levels at week 4 that were maintained until week 24, an
      effect associated with increased levels of bone formation markers that were
      significant as compared with placebo only for PINP and only at 4 weeks (P < 0.01
      for both TCZ doses). TCZ induced significant decreases in the bone degradation
      markers CTX-I and ICTP, providing initial evidence of a beneficial effect on bone
      turnover. TCZ-treated patients who met the American College of Rheumatology 50%
      improvement criteria (achieved an ACR50 response) or achieved clinical remission
      (as determined by a Disease Activity Score in 28 joints <2.6) at week 24 had
      greater reductions in ICTP, HELIX-II, and MMP-3 levels as compared with ACR50
      nonresponders. CONCLUSION: TCZ combined with MTX reduces systemic bone
      resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels, which
      provides evidence of a limitation of joint damage and possible beneficial effects
      on skeletal structure in patients with established moderate-to-severe RA.

PMID- 20039427
TI  - The transcription factor Fra-2 regulates the production of extracellular matrix
      in systemic sclerosis.
AB  - OBJECTIVE: Fra-2 belongs to the activator protein 1 family of transcription
      factors. Mice transgenic for Fra-2 develop a systemic fibrotic disease with
      vascular manifestations similar to those of systemic sclerosis (SSc). The aim of
      the present study was to investigate whether Fra-2 plays a role in the
      pathogenesis of SSc and to identify the molecular mechanisms by which Fra-2
      induces fibrosis. METHODS: Dermal thickness and the number of myofibroblasts were
      determined in skin sections from Fra-2-transgenic and wild-type mice. The
      expression of Fra-2 in SSc patients and in animal models of SSc was analyzed by
      real-time polymerase chain reaction and immunohistochemistry. Fra-2, transforming
      growth factor beta (TGFbeta), and ERK signaling in SSc fibroblasts were inhibited
      using small interfering RNA, neutralizing antibodies, and small-molecule
      inhibitors. RESULTS: Fra-2-transgenic mice developed a skin fibrosis with
      increases in dermal thickness and increased myofibroblast differentiation
      starting at age 12 weeks. The expression of Fra-2 was up-regulated in SSc
      patients and in different mouse models of SSc. Stimulation with TGFbeta and
      platelet-derived growth factor (PDGF) significantly increased the expression of
      Fra-2 in SSc fibroblasts and induced DNA binding of Fra-2 in an ERK-dependent
      manner. Knockdown of Fra-2 potently reduced the stimulatory effects of TGFbeta
      and PDGF and decreased the release of collagen from SSc fibroblasts. CONCLUSION:
      We demonstrate that Fra-2 is overexpressed in SSc and acts as a novel downstream
      mediator of the profibrotic effects of TGFbeta and PDGF. Since transgenic
      overexpression of Fra-2 causes not only fibrosis but also vascular disease, Fra-2
      might be an interesting novel candidate for molecular-targeted therapies for SSc.

PMID- 20039428
TI  - Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten
      patients with neonatal-onset multisystem inflammatory disease/chronic infantile
      neurologic, cutaneous, articular syndrome.
AB  - OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) are a group of rare
      autoinflammatory diseases. Neonatal-onset multisystem inflammatory disease
      (NOMID)/chronic infantile neurologic, cutaneous, articular syndrome (CINCA
      syndrome) is the most severe phenotype, with fever, rash, articular
      manifestations, and neurologic and neurosensory involvement. CAPS are caused by
      mutations in CIAS1, the gene encoding NLRP3, which plays a critical role in
      interleukin-1 (IL-1) processing. Anakinra, an IL-1 receptor antagonist, has been
      shown to be an effective treatment; however, data on long-term efficacy and
      safety have been sparse. This study was undertaken to assess the long-term
      efficacy and safety of anakinra treatment in patients with NOMID/CINCA syndrome.
      METHODS: We retrospectively analyzed the medical records of NOMID/CINCA syndrome
      patients referred to 2 centers, who had started anakinra treatment before June
      2007. RESULTS: There were 10 patients with NOMID/CINCA syndrome who had been
      treated with anakinra. The patients' ages at the time anakinra treatment was
      initiated ranged from 3 months to 20 years. They had been followed up for 26-42
      months. Sustained efficacy in the treatment of systemic inflammation and, in some
      cases, neurologic involvement and growth parameters, was achieved. The dosage of
      anakinra required for efficacy ranged from 1 to 3 mg/kg/day in the 8 oldest
      patients and from 6 to 10 mg/kg/day in the 2 youngest. Residual central nervous
      system inflammation and deafness persisted in some patients, especially if there
      had been a delay in diagnosis and treatment. Secondary amyloidosis persisted in
      cases in which it was present at treatment initiation, but no new lesions
      developed. No effect on overgrowth arthropathy was observed. Adverse events
      consisted of mild injection-site reactions. CONCLUSION: The present results
      indicate that anakinra treatment is effective over the long term in NOMID/CINCA
      syndrome. However, treatment has to be initiated before irreversible lesions
      develop, and, particularly in very young patients, dosage adjustment is required.

PMID- 20039430
TI  - Functional autoantibodies against serpin E2 in rheumatoid arthritis.
AB  - OBJECTIVE: To search for novel autoantibodies in patients with rheumatoid
      arthritis (RA) in an effort to better understand the processes of joint
      destruction in this disease. METHODS: Using a modified SEREX technique and
      complementary DNA derived from RA synovium, serpin E2 was identified as a novel
      autoantigen and was analyzed by immunohistochemistry. Levels of anti-serpin E2
      autoantibodies in serum and synovial fluid from patients with RA, osteoarthritis
      (OA), psoriatic arthritis, and ankylosing spondylitis, and/or from healthy
      individuals were assessed by enzyme-linked immunosorbent assay. Since serpin E2
      is an inhibitor of serine proteases, we studied the inhibitory activity of serpin
      E2 toward its target, urokinase plasminogen activator (uPA), in vitro in the
      presence of isolated anti-serpin E2 autoantibodies and in vivo using the uPA
      activity assay. RESULTS: We identified autoantibodies against serpin E2 by the
      SEREX technique. Serpin E2 was overexpressed in RA synovial tissues as compared
      with OA synovial tissues. Significantly higher levels of anti-serpin E2
      autoantibodies were present in samples of synovial fluid (28%) and serum (22%)
      from RA patients as compared with OA patients (0 and 6%, respectively) or with
      healthy individuals (6% of sera). Most importantly, anti-serpin E2 autoantibodies
      isolated from RA sera reversed the inhibitory activity of serpin E2 by 70%.
      Furthermore, the levels of anti-serpin E2 autoantibodies correlated with the uPA
      activity in vivo. CONCLUSION: This study characterizes a functional property of a
      novel autoantibody in RA. Since anti-serpin E2 autoantibodies interfere with the
      inhibitory activity of serpin E2 toward serine proteases, they might facilitate
      the joint destruction in RA.

PMID- 20039429
TI  - Nonrenal disease activity following mycophenolate mofetil or intravenous
      cyclophosphamide as induction treatment for lupus nephritis: findings in a
      multicenter, prospective, randomized, open-label, parallel-group clinical trial.
AB  - OBJECTIVE: To assess the effect of mycophenolate mofetil compared with
      intravenous pulses of cyclophosphamide on the nonrenal manifestations of lupus
      nephritis. METHODS: Patients with active lupus nephritis (renal biopsy class III,
      IV, or V) were recruited for the study (n = 370) and treated with mycophenolate
      mofetil (target dosage 3 gm/day) or intravenous cyclophosphamide (0.5-1.0
      gm/m(2)/month), plus tapered prednisone, for 24 weeks. Nonrenal outcomes were
      determined using measures of whole body disease activity, including the British
      Isles Lupus Assessment Group (BILAG) disease activity index, the Safety of
      Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and immunologic
      variables. RESULTS: Both treatments were effective on whole body disease activity
      in the systems examined, as indicated by changes in the classic BILAG index. With
      either treatment, remission was induced, notably in the mucocutaneous,
      musculoskeletal, cardiovascular/respiratory, and vasculitis systems, and flares
      were rare, as measured by the SELENA-SLEDAI. Levels of complement C3, C4, and
      CH50 and titers of anti-double-stranded DNA antibodies were normalized after
      treatment with either mycophenolate mofetil or intravenous cyclophosphamide.
      CONCLUSION: In addition to the efficacy of both treatments on the renal system,
      this analysis showed that remission could also be induced in other systems. There
      was no clear difference in efficacy between mycophenolate mofetil and intravenous
      cyclophosphamide in ameliorating either the renal or nonrenal manifestations.
      Mycophenolate mofetil is, therefore, a suitable alternative to cyclophosphamide
      for the treatment of renal and nonrenal disease manifestations in patients with
      biopsy-proven lupus nephritis.

PMID- 20039431
TI  - ANTI-CD3 therapy expands the numbers of CD4+ and CD8+ Treg cells and induces
      sustained amelioration of collagen-induced arthritis.
AB  - OBJECTIVE: To assess the therapeutic potential of anti-CD3 monoclonal antibodies
      (mAb) for rheumatoid arthritis, using collagen-induced arthritis as an animal
      model. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II
      collagen. After disease onset, a single injection of anti-CD3 mAb (20
      microg/mouse) was administered, and arthritis severity was monitored over a 10
      day period. RESULTS: Anti-CD3 mAb treatment resulted in a sustained reduction in
      disease activity, which was associated with an increase in the proportion of
      naturally occurring CD4+CD25+FoxP3+ regulatory T (Treg) cells and the generation
      of a population of CD8+CD25+FoxP3+ Treg cells. Anti-CD3 mAb treatment did not
      alter the capacity of CD4+ Treg cells to suppress effector T cell proliferation
      and interferon-gamma (IFNgamma) production in vitro. However, CD4+ Treg cells
      from both anti-CD3 mAb-treated and control mice were unable to suppress
      interleukin-17 (IL-17) production. In contrast, CD8+ Treg cells induced by anti
      CD3 therapy suppressed IL-17 production as well as CD4+ T cell proliferation and
      IFNgamma production. CONCLUSION: These results show that anti-CD3 mAb treatment
      has important therapeutic potential for rheumatoid arthritis and has the capacity
      to generate antiarthritic CD8+ Treg cells and expand the relative numbers of CD4+
      Treg cells.

PMID- 20039432
TI  - Antibodies to several citrullinated antigens are enriched in the joints of
      rheumatoid arthritis patients.
AB  - OBJECTIVE: High titers of specific anti-citrullinated protein antibodies (ACPAs)
      are frequently present in the serum of rheumatoid arthritis (RA) patients, but
      their presence in synovial fluid is less well characterized. The purpose of this
      study was to compare the levels of antibody to 4 well-defined citrullinated
      candidate RA autoantigens in serum and synovial fluid and to determine whether
      antibodies to one citrullinated antigen are dominant over another. Furthermore,
      we studied their relationships with mutated citrullinated vimentin (MCV), a newly
      identified RA-specific serum assay, and the classic cyclic citrullinated peptide
      (CCP) in the synovial fluid of well-defined HLA-DR groups. METHODS: Paired serum
      and synovial fluid samples from 290 RA patients and serum samples from 100 age-
      and sex-matched healthy controls were analyzed for the presence of anti-MCV and
      anti-CCP antibodies and for reactivity to citrullinated fibrinogen, alpha
      enolase, type II collagen, and vimentin. A total of 219 of the 290 patients were
      genotyped for the HLA-DR shared epitope alleles. RESULTS: Significantly higher
      proportions of antibodies against all RA-associated citrullinated antigens were
      found in synovial fluid as compared with serum. This was also true for the MCV
      and CCP responses but not for non-RA-associated anti-tetanus toxoid antibodies.
      As expected, we found a high correlation between citrullinated vimentin and MCV
      responses. All synovial fluid ACPAs were predominantly associated with HLA
      DRB1*04 alleles and were confined to the CCP+/MCV+ subset of patients.
      CONCLUSION: MCV and CCP positivity represent a similar subset of RA patients,
      whereas ACPAs with different fine specificities fall into subgroups of anti
      CCP+/anti-MCV+ patients. The levels of all specific ACPAs were elevated in
      synovial fluid, suggesting that there is local antibody production and/or
      retention of ACPAs at the site of inflammation governed by RA-predisposing genes.

PMID- 20039433
TI  - Novel role of plasmacytoid dendritic cells in humans: induction of interleukin-10
      producing Treg cells by plasmacytoid dendritic cells in patients with rheumatoid
      arthritis responding to therapy.
AB  - OBJECTIVE: Reestablishing immune tolerance and long-term suppression of disease
      represent major therapeutic goals in rheumatoid arthritis (RA). Dendritic cells
      (DCs) likely play a central role in such regulation via the expansion and/or
      induction of Treg cells. The present study was undertaken to explore the
      contribution of DCs to the development of Treg cells in a human autoimmune
      disease setting. METHODS: DC subsets were characterized by flow cytometry in the
      peripheral blood and synovial fluid of patients with RA. Proliferation of and
      cytokine release by naive CD4+CD25- T cells were measured in cocultures of these
      cells with DCs from patients with RA and healthy controls. The suppressive
      capacity of DC-polarized T cells was explored in vitro by a standard suppression
      assay. RESULTS: Only very low numbers of both plasmacytoid DCs (CD303+) and
      myeloid DCs (CD1c+) were present in the peripheral blood of patients with active
      RA. In contrast, patients with therapy-induced remission of RA exhibited higher
      numbers of circulating plasmacytoid DCs. Mature plasmacytoid DCs from RA patients
      with low disease activity, but not those from healthy controls, expressed high
      levels of indoleamine 2,3-dioxygenase and promoted the differentiation of
      allogeneic naive CD4+CD25- T cells into interleukin-10-secreting Treg cells, or
      Tr1 cells, that showed poor proliferation in vitro. Importantly, these
      plasmacytoid DC-primed Treg cells potently suppressed the proliferation of
      autologous naive CD4+ T cells, in a dose-dependent manner. CONCLUSION: These
      results demonstrate, for the first time, that human plasmacytoid DCs may be
      educated within the rheumatoid microenvironment to acquire a tolerogenic
      phenotype. Modulation of the immune response by plasmacytoid DCs might provide
      novel immune-based therapies in autoimmunity and transplantation.

PMID- 20039434
TI  - Inhibition of synovial hyperplasia, rheumatoid T cell activation, and
      experimental arthritis in mice by sulforaphane, a naturally occurring
      isothiocyanate.
AB  - OBJECTIVE: To investigate whether sulforaphane (SFN), an isothiocyanate derived
      from cruciferous vegetables such as broccoli, regulates synoviocyte hyperplasia
      and T cell activation in rheumatoid arthritis (RA). METHODS: Synoviocyte survival
      was assessed by MTT assay. The levels of Bcl-2, Bax, p53, and pAkt were
      determined by Western blot analysis. Cytokine concentrations in culture
      supernatants from mononuclear cells were analyzed by enzyme-linked immunosorbent
      assay. The in vivo effects of SFN were examined in mice with experimentally
      induced arthritis. RESULTS: SFN induced synoviocyte apoptosis by modulating the
      expression of Bcl-2/Bax, p53, and pAkt. In addition, nonapoptotic doses of SFN
      inhibited T cell proliferation and the production of interleukin-17 (IL-17) and
      tumor necrosis factor alpha (TNFalpha) by RA CD4+ T cells stimulated with anti
      CD3 antibody. Anti-CD3 antibody-induced increases in the expression of retinoic
      acid-related orphan receptor gammat and T-bet were also repressed by SFN.
      Moreover, the intraperitoneal administration of SFN to mice suppressed the
      clinical severity of arthritis induced by injection of type II collagen (CII),
      the anti-CII antibody levels, and the T cell responses to CII. The production of
      IL-17, TNFalpha, IL-6, and interferon-gamma by lymph node cells and spleen cells
      from these mice was markedly reduced by treatment with SFN. Anti-CII antibody
      induced arthritis in mice was also alleviated by SFN injection. CONCLUSION: SFN
      was found to inhibit synovial hyperplasia, activated T cell proliferation, and
      the production of IL-17 and TNFalpha by rheumatoid T cells in vitro. The
      antiarthritic and immune regulatory effects of SFN, which were confirmed in vivo,
      suggest that SFN may offer a possible treatment option for RA.

PMID- 20039435
TI  - Tag SNP selection using particle swarm optimization.
AB  - Single nucleotide polymorphisms (SNPs) are the most abundant form of genetic
      variations amongst species. With the genome-wide SNP discovery, many genome-wide
      association studies are likely to identify multiple genetic variants that are
      associated with complex diseases. However, genotyping all existing SNPs for a
      large number of samples is still challenging even though SNP arrays have been
      developed to facilitate the task. Therefore, it is essential to select only
      informative SNPs representing the original SNP distributions in the genome (tag
      SNP selection) for genome-wide association studies. These SNPs are usually chosen
      from haplotypes and called haplotype tag SNPs (htSNPs). Accordingly, the scale
      and cost of genotyping are expected to be largely reduced. We introduce binary
      particle swarm optimization (BPSO) with local search capability to improve the
      prediction accuracy of STAMPA. The proposed method does not rely on block
      partitioning of the genomic region, and consistently identified tag SNPs with
      higher prediction accuracy than either STAMPA or SVM/STSA. We compared the
      prediction accuracy and time complexity of BPSO to STAMPA and an SVM-based
      (SVM/STSA) method using publicly available data sets. For STAMPA and SVM/STSA,
      BPSO effective improved prediction accuracy for smaller and larger scale data
      sets. These results demonstrate that the BPSO method selects tag SNP with higher
      accuracy no matter the scale of data sets is used.

PMID- 20039436
TI  - Using the rate of respiration to monitor events in the infection of Escherichia
      coli cultures by bacteriophage T4.
AB  - The growing interest in applications of bacteriophages creates a need for
      improvements in the production processes. Continuous monitoring of the phage
      production is an essential aspect of any control strategy and, at present, there
      is no completely satisfactory option. The approach presented here uses IR
      spectrometry to continuously measure the rate of respiration (CO(2) released) of
      Escherichia coli infected by phage T4 at various multiplicities of infection
      (MOI). Within the trends in these data, or in other aspects of the rate of
      respiration, it was possible to reliably and reproducibly identify five features
      that reflected specific events in the infection process. These included two
      events in the host cell apparent growth rate and events in the magnitude of the
      host cell density, in the measurement of OD(600) or in the specific rate of
      respiration. All of these correlations were within 95% confidence showing that
      they are suitable for the monitoring and control of E. coli populations infected
      by phage T4. This method is reliable, cheap, and can be operated in-line and in
      real time.

PMID- 20039437
TI  - Effect of disaccharides on the stabilization of bovine trypsin against detergent
      and autolysis.
AB  - Osmolytes have been reported to stabilize biomolecules and even whole organisms
      against exposure to adverse environmental conditions. In this work, we report for
      the first time the use of some of these osmolytes, viz., the disaccharides
      trehalose and sucrose, in the stabilization of bovine trypsin against exposure to
      the anionic detergent sodium dodecyl sulfate and autolysis. Exposure of trypsin
      to SDS at a molar ratio of 1:45 led to decrease in trypsin activity by 61%. In
      the presence of 1 M sucrose and 1 M trehalose, the residual trypsin activity was
      found to increase to that of original enzyme activity. These two disaccharides
      were also found to slow down the rate of autolysis, resulting in residual
      activities of 80 and 88%, respectively, after incubation for 24 h. Active site
      titration showed retention of the fraction of active sites in the presence of
      trehalose. Fluorescence and CD spectroscopies were used to decipher the probable
      mechanism of this protective role of the disaccharides. Although complete
      resumption of secondary structure was not seen in the presence of the two
      disaccharides, the spectra of trypsin in the presence of stabilizers resembled
      the spectrum of native trypsin and were significantly different from the spectrum
      of detergent-denatured enzyme. Correlating the data obtained from spectroscopy
      with those obtained from activity assay, we propose that the retention of
      secondary structure of the enzyme is largely responsible for the retention of the
      functionally active form of trypsin.

PMID- 20039438
TI  - Morphological and morphometric changes of pituitary lactotrophs of viscacha
      (Lagostomus maximus maximus) in relation to reproductive cycle, age, and sex.
AB  - Lactotrophs in pituitary pars distalis (PD) of viscacha were studied by
      immunohistochemistry and morphometric analysis in the following groups: 1) adult
      males throughout the reproductive cycle (reproductive, gonadal regression, and
      recovery periods), 2) melatonin-treated adults, 3) castrated adults, 4)
      prepubertal, 5) non-pregnant females, and 6) pregnant females (early, mid, and
      late pregnancy). Immunopositive percentage area (%IA), cell percentage in PD (%
      PDC), number of cells per reference area (no.cell/RA), major cellular and nuclear
      diameters were analyzed. Lactotrophs were mainly localized in the ventro-medial
      region and the caudal extreme of PD. In the male viscachas, they were isolated in
      small and big groups, close to blood vessels and near follicles. These cells were
      pleomorphic and with a heterogeneous cytoplasmic immunolabeling pattern. In the
      adult males of the gonadal regression period the morphometric parameters were the
      lowest. Most parameters of lactotrophs in the prepubertal were significantly
      lower than in the adult males in the reproductive period. In the melatonin
      treated animals and in castrated animals there was a decrease in %IA, %PDC, and
      no.cell/RA. In the females, the morphometric parameters increased at the end of
      pregnancy. Non-pregnant females exhibited a higher immunopositive area and
      number, but a smaller size of cells than males. Our results showed that in the
      adult male viscacha, lactotrophs vary seasonally, probably due to the photoperiod
      effect through melatonin. Besides the changes observed after castration, in
      prepubertal animals, in adults of different sex, and during pregnancy suggest
      that the gonadal steroid hormones might modify the lactotrophs activity.

PMID- 20039439
TI  - The developmental remodeling of eye-specific afferents in the ferret dorsal
      lateral geniculate nucleus.
AB  - Eye-specific projections to the dorsal lateral geniculate nucleus (dLGN) serve as
      a model for exploring how precise patterns of circuitry form during development
      in the mammalian central nervous system. Using a combination of dual-label
      anterograde retinogeniculate tracing and Nissl-staining, we studied the patterns
      of eye-specific afferents and cellular laminae in the dLGN of the pigmented sable
      ferret at eight developmental timepoints between birth and adulthood. Each time
      point was investigated in the three standard orthogonal planes of section,
      allowing us to generate a complete anatomical map of eye-specific development in
      this species. We find that eye-specific retinal ganglion cell axon segregation
      varies according to location in the dLGN, with the principle contralateral (A)
      and ipsilateral layers (A1) maturing first, followed by the contralateral and
      ipsilateral C laminae. Cytoarchitectural lamination lags behind eye-specific
      segregation, except in the C laminae where underlying cellular layers never
      develop to accompany eye-specific afferent domains. The emergence of On/Off
      sublaminae occurs following eye-specific segregation in this species. On the
      basis of these findings, we constructed a three-dimensional map of eye-specific
      channels in the developing and mature ferret dLGN.

PMID- 20039440
TI  - A cell leakproof PLGA-collagen hybrid scaffold for cartilage tissue engineering.
AB  - A cell leakproof porous poly(DL-lactic-co-glycolic acid) (PLGA)-collagen hybrid
      scaffold was prepared by wrapping the surfaces of a collagen sponge except the
      top surface for cell seeding with a bi-layered PLGA mesh. The PLGA-collagen
      hybrid scaffold had a structure consisting of a central collagen sponge formed
      inside a bi-layered PLGA mesh cup. The hybrid scaffold showed high mechanical
      strength. The cell seeding efficiency was 90.0% when human mesenchymal stem cells
      (MSCs) were seeded in the hybrid scaffold. The central collagen sponge provided
      enough space for cell loading and supported cell adhesion, while the bi-layered
      PLGA mesh cup protected against cell leakage and provided high mechanical
      strength for the collagen sponge to maintain its shape during cell culture. The
      MSCs in the hybrid scaffolds showed round cell morphology after 4 weeks culture
      in chondrogenic induction medium. Immunostaining demonstrated that type II
      collagen and cartilaginous proteoglycan were detected in the extracellular
      matrices. Gene expression analyses by real-time PCR showed that the genes
      encoding type II collagen, aggrecan, and SOX9 were upregulated. These results
      indicated that the MSCs differentiated and formed cartilage-like tissue when
      being cultured in the cell leakproof PLGA-collagen hybrid scaffold. The cell
      leakproof PLGA-collagen hybrid scaffolds should be useful for applications in
      cartilage tissue engineering.

PMID- 20039441
TI  - Product and contaminant measurement in bioprocess development by SELDI-MS.
AB  - Bioprocesses for therapeutic protein production typically require significant
      resources to be invested in their development. Underlying these efforts are
      analytical methods, which must be fit for the purpose of monitoring product and
      contaminants in the process. It is highly desirable, especially in early-phase
      development when material and established analytical methods are limiting, to be
      able to determine what happens to the product and impurities at each process step
      with small sample volumes in a rapid and readily performed manner. This study
      evaluates the utility of surface-enhanced laser desorption ionization mass
      spectroscopy (SELDI-MS), known for its rapid analysis and minimal sample volumes,
      as an analytical process development tool. In-process samples from an E. coli
      process for apolipoprotein A-IM (ApoA-IM) manufacture were used along with
      traditional analytical methods such as HPLC to check the SELDI-MS results. ApoA
      IM is a naturally occurring variant of ApoA-I that appears to confer protection
      against cardiovascular disease to those that carry the mutated gene. The results
      show that, unlike many other analytical methods, SELDI-MS can handle early
      process samples that contain complex mixtures of biological molecules with
      limited sample pretreatment and thereby provide meaningful process-relevant
      information. At present, this technique seems most suited to early-phase
      development particularly when methods for traditional analytical approaches are
      still being established.

PMID- 20039442
TI  - Impact of freezing on pH of buffered solutions and consequences for monoclonal
      antibody aggregation.
AB  - Freezing of biologic drug substance at large scale is an important unit operation
      that enables manufacturing flexibility and increased use-period for the material.
      Stability of the biologic in frozen solutions is associated with a number of
      issues including potentially destabilizing pH changes. The pH changes arise from
      temperature-associated change in the pK(a)s, solubility limitations, eutectic
      crystallization, and cryoconcentration. The pH changes for most of the common
      protein formulation buffers in the frozen state have not been systematically
      measured. Sodium phosphate buffer, a well-studied system, shows the greatest
      change in pH when going from +25 to -30 degrees C. Among the other buffers,
      histidine hydrochloride, sodium acetate, histidine acetate, citrate, and
      succinate, less than 1 pH unit change (increase) was observed over the
      temperature range from +25 to -30 degrees C, whereas Tris-hydrochloride had an
      approximately 1.2 pH unit increase. In general, a steady increase in pH was
      observed for all these buffers once cooled below 0 degrees C. A formulated IgG2
      monoclonal antibody in histidine buffer with added trehalose showed the same pH
      behavior as the buffer itself. This antibody in various formulations was subject
      to freeze/thaw cycling representing a wide process (phase transition) time range,
      reflective of practical situations. Measurement of soluble aggregates after
      repeated freeze-thaw cycles shows that the change in pH was not a factor for
      aggregate formation in this case, which instead is governed by the presence or
      absence of noncrystallizing cryoprotective excipients. In the absence of a
      cryoprotectant, longer phase transition times lead to higher aggregation.

PMID- 20039444
TI  - Limitations in assessment of mucosal healing in inflammatory bowel disease.
AB  - An emerging parameter to define the effectiveness of new therapeutic agents in
      clinical trials, and by extension, for use in day-to-day clinical practice has
      been labeled mucosal healing. It has been hypothesized that complete healing of
      the intestinal mucosa in inflammatory bowel diseases should result in reduced
      disease complications, reduced hospitalization and reduced surgical treatment. By
      implication, the natural history of inflammatory bowel disease might then be
      altered. Measurement of mucosal healing, however, is largely observational,
      requiring repeated invasive endoscopic examinations, sometimes with mucosal
      biopsies. Other indirect imaging methods may play a role in this assessment along
      with other surrogate markers, including intestinal permeability. These
      measurements may have significant limitations that prohibit precise correlation
      with symptom-based disease activity indices in clinical trials. This likely
      reflects the dynamic nature of this evolving and individualized inflammatory
      process that tends to be focused, but not limited, to the mucosa of the
      intestinal tract.

PMID- 20039443
TI  - Hepatocyte cryopreservation: is it time to change the strategy?
AB  - Liver cell transplantation presents clinical benefit in patients with inborn
      errors of metabolism as an alternative, or at least as a bridge, to orthotopic
      liver transplantation. The success of such a therapeutic approach remains limited
      by the quality of the transplanted cells. Cryopreservation remains the best
      option for long-term storage of hepatocytes, providing a permanent and sufficient
      cell supply. However, isolated adult hepatocytes are poorly resistant to such a
      process, with a significant alteration both at the morphological and functional
      levels. Hence, the aim of the current review is to discuss the state of the art
      regarding widely-used hepatocyte cryopreservation protocols, as well as the
      assays performed to analyse the post-thawing cell quality both in vitro and in
      vivo. The majority of studies agree upon the poor quality and efficiency of
      cryopreserved/thawed hepatocytes as compared to freshly isolated hepatocytes.
      Intracellular ice formation or exposure to hyperosmotic solutions remains the
      main phenomenon of cryopreservation process, and its effects on cell quality and
      cell death induction will be discussed. The increased knowledge and understanding
      of the cryopreservation process will lead to research strategies to improve the
      viability and the quality of the cell suspensions after thawing. Such strategies,
      such as vitrification, will be discussed with respect to their potential to
      significantly improve the quality of cell suspensions dedicated to liver cell
      based therapies.

PMID- 20039445
TI  - Loss of CD103+ intestinal dendritic cells during colonic inflammation.
AB  - AIM: To investigate possible differences in dendritic cells (DC) within
      intestinal tissue of mice before and after induction of colitis. METHODS: Mucosal
      DC derived from intestinal tissue, as well as from mesenteric lymph nodes and
      spleen, were analyzed by fluorescence activated cell sorting (FACS) analysis.
      Supernatants of these cells were analyzed for secretion of different pro- and
      anti-inflammatory cytokines. Immunohistochemistry and immunofluorescence were
      performed on cryosections of mucosal tissue derived from animals with colitis as
      well as from healthy mice. RESULTS: It was shown that DC derived from healthy
      intestinal lamina propria (LP) represented an immature phenotype as characterized
      by low-level expression of costimulatory cytokines. In contrast to DC from spleen
      and mesenteric lymph nodes (MLN) that secreted proinflammatory cytokines, LP-DC
      produced high levels of the anti-inflammatory cytokine IL-10. After induction of
      murine colitis in a CD4(+)CD62L(+) transfer model or in chronic dextran sulfate
      sodium-colitis, a marked increase of activated CD80(+) DC could be observed
      within the inflamed colonic tissue. Interestingly, in contrast to splenic DC, a
      significant population of DC within MLN and colonic LP expressed the mucosal
      integrin CD103 which was lost during colitis. CONCLUSION: The constitutive
      secretion of anti-inflammatory cytokines by immature DC within the intestinal LP
      might regulate the homeostatic balance between mucosal immunity and tolerance.
      CD103(+) DC could mediate this important function.

PMID- 20039446
TI  - Antibiotics and probiotics in chronic pouchitis: a comparative proteomic
      approach.
AB  - AIM: To profile protein expression in mucosal biopsies from patients with chronic
      refractory pouchitis following antibiotic or probiotic treatment, using a
      comparative proteomic approach. METHODS: Two-dimensional polyacrylamide gel
      electrophoresis and matrix-assisted laser desorption/ionization-time of flight
      mass spectrometry were used to characterize the changes related to antibiotic
      therapy in the protein expression profiles of biopsy samples from patients with
      chronic refractory pouchitis. The same proteomic approach was applied to identify
      differentially expressed proteins in the non-inflamed pouch before and after
      probiotic administration. RESULTS: In the first set of 2D gels, 26 different
      proteins with at least 2-fold changes in their expression levels between the
      pouchitis condition and antibiotic-induced remission were identified. In the
      second set of analysis, the comparison between mucosal biopsy proteomes in the
      normal and probiotic-treated pouch resulted in 17 significantly differently
      expressed proteins. Of these, 8 exhibited the same pattern of deregulation as in
      the pouchitis/pouch remission group. CONCLUSION: For the first time, 2D protein
      maps of mucosal biopsies from patients with ileal pouch-anal anastomosis were
      provided, and differentially expressed proteins following antibiotic/probiotic
      treatment were identified.

PMID- 20039447
TI  - Is there an association between Helicobacter pylori in the inlet patch and globus
      sensation?
AB  - AIM: To determine the association between Helicobacter pylori (H. pylori) and
      globus sensation (GS) in the patients with cervical inlet patch. METHODS: Sixty
      eight patients with esophageal inlet patches were identified from 6760
      consecutive patients undergoing upper gastrointestinal endoscopy prospectively.
      In these 68 patients with cervical inlet patches, symptoms of globus sensation
      (lump in the throat), hoarseness, sore throat, frequent clearing of the throat,
      cough, dysphagia, odynophagia of at least 3 mo duration was questioned prior to
      endoscopy. RESULTS: Cervical heterotopic gastric mucosa (CHGM) was found in 68 of
      6760 patients. The endoscopic prevalence of CHGM was determined to be 1%. H.
      pylori was identified in 16 (23.5%) of 68 patients with inlet patch. Fifty-three
      patients were classified as CHGM II. This group included 48 patients with globus
      sensation, 4 patients with chronic cough and 1 patient with hoarseness. All the
      patients who were H. pylori (+) in cervical inlet patches had globus sensation.
      CONCLUSION: Often patients with CHGM have a long history of troublesome throat
      symptoms. We speculate that disturbances in globus sensation are like non-ulcer
      dyspepsia.

PMID- 20039448
TI  - Atrial natriuretic peptide signal pathway upregulated in stomach of
      streptozotocin-induced diabetic mice.
AB  - AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric
      mucosa and the relationship between the ANP/natriuretic peptide receptor type A
      (NPR-A) pathway and diabetic gastroparesis. METHODS: Male imprinting control
      region (ICR) mice (4 wk old) were divided into two groups: control mice, and
      streptozotocin-induced diabetic mice. Eight weeks after injection, spontaneous
      gastric contraction was recorded by using physiography in control and
      streptozotocin-induced diabetic mice. The ANP-positive cells in gastric mucosa
      and among dispersed gastric epithelial cells were detected by using
      immunohistochemistry and flow cytometry, respectively. ANP and natriuretic
      peptide receptor type A (NPR-A) gene expression in gastric tissue was observed by
      using the reverse transcriptase polymerase chain reaction. RESULTS: The frequency
      of spontaneous gastric contraction was reduced from 12.9 +/- 0.8 cycles/min in
      the control group to 8.4 +/- 0.6 cycles/min in the diabetic mice (n = 8, P <
      0.05). However, the amplitude of contraction was not significantly affected in
      the diabetic group. The depletion of interstitial cells of Cajal in the gastric
      muscle layer was observed in the diabetic mice. ANP-positive cells were
      distributed in the gastric mucosal layer and the density index of ANP-positive
      cells was increased from 20.9 +/- 2.2 cells/field in control mice to 51.8 +/- 2.9
      cells/field in diabetic mice (n = 8, P < 0.05). The percentage of ANP-positive
      cells among the dispersed gastric epithelial cells was increased from 10.0% +/-
      0.9% in the control mice to 41.2% +/- 1.0% in the diabetic mice (n = 3, P <
      0.05). ANP and NPR-A genes were both expressed in mouse stomach, and the
      expression was significantly increased in the diabetic mice. CONCLUSION: These
      results suggest that the ANP/NPR-A signaling pathway is upregulated in
      streptozotocin-induced diabetic mice, and contributes to the development of
      diabetic gastroparesis.

PMID- 20039449
TI  - Double balloon enteroscopy in children: diagnosis, treatment, and safety.
AB  - AIM: To assess the feasibility and utility of double balloon enteroscopy (DBE) in
      the management of small bowel diseases in children. METHODS: Fourteen patients
      (10 males) with a median age of 12.9 years (range 8.1-16.7) underwent DBE; 5 for
      Peutz-Jeghers syndrome (PJ syndrome), 2 for chronic abdominal pain, 4 for obscure
      gastrointestinal (GI) bleeding, 2 with angiomatous malformations (1 blue rubber
      bleb nevus syndrome) having persistent GI bleeding, and 1 with Cowden's syndrome
      with multiple polyps and previous intussusception. Eleven procedures were
      performed under general anesthesia and 3 with deep sedation. RESULTS: The entire
      small bowel was examined in 6 patients, and a length between 200 cm and 320 cm
      distal to pylorus in the remaining 8. Seven patients had both antegrade (trans
      oral) and retrograde (trans-anal and via ileostomy) examinations. One patient
      underwent DBE with planned laparoscopic assistance. The remaining 6 had trans
      oral examination only. The median examination time was 118 min (range 95-195). No
      complications were encountered. Polyps were detected and successfully removed in
      all 5 patients with PJ syndrome, in a patient with tubulo-villous adenoma of the
      duodenum, in a patient with significant anemia and occult bleeding, and in a
      patient with Cowden's syndrome. A diagnosis was made in a patient with multiple
      angiomata not amenable to endotherapy, and in 1 with a discrete angioma which was
      treated with argon plasma coagulation. The source of bleeding was identified in a
      further patient with varices. DBE was normal or revealed minor mucosal friability
      in the remaining 3 patients. Hence a diagnostic yield of 11/14 with therapeutic
      success in 9/14 was achieved. CONCLUSION: Double balloon enteroscopy can be a
      useful diagnostic and therapeutic tool for small bowel disease in children,
      allowing endo-therapeutic intervention beyond the reach of the conventional
      endoscope.

PMID- 20039451
TI  - Systematic review of randomised controlled trials: probiotics for functional
      constipation.
AB  - AIM: To systematically evaluate and update evidence on the efficacy and safety of
      probiotic supplementation for the treatment of constipation. METHODS: The
      MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched in May 2009
      for randomised controlled trials (RCTs) performed in paediatric or adult
      populations related to the study aim. RESULTS: We included five RCTs with a total
      of 377 subjects (194 in the experimental group and 183 in the control group). The
      participants were adults (three RCTs, n = 266) and children (two RCTs, n = 111)
      with constipation. In adults, data suggests a favourable effect of treatment with
      Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota, and Escherichia
      coli Nissle 1917 on defecation frequency and stool consistency. In children, L.
      casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect.
      CONCLUSION: Until more data are available, we believe the use of probiotics for
      the treatment of constipation condition should be considered investigational.

PMID- 20039450
TI  - Z-line examination by the PillCam SB: prospective comparison of three ingestion
      protocols.
AB  - AIM: To evaluate the Z-line visualization by the PillCam SB2 using three
      different ingestion protocols. METHODS: Ninety consecutive patients undergoing
      small bowel capsule endoscopy (SBCE) between January and May 2008 were included
      in the study. They swallowed the capsule in the standing (Group A = 30), supine
      (Group B = 30) and right supine positions (Group C = 30). Baseline patient
      characteristics, difficulties in capsule ingestion, esophageal transit times
      (ETT) and Z-line visualization were noted. RESULTS: No significant differences
      were found between the groups with regard to baseline patient characteristics,
      ingestion difficulties and complete SB examinations (P > 0.05). At least 1 frame
      of the Z-line was detected in 15.8%, 46.7% and 90% of patients in groups A, B and
      C, respectively (P < 0.001). The average number of Z-line images was 0.21 +/-
      0.53, 3.23 +/- 6.59 and 5.53 +/- 7.55 and the mean % of the Z-line detected was
      71.3, 25.1 and 8.3, in groups A, B and C, respectively (both P < 0.001). ETT
      times were longer in the supine group followed by the right supine and the
      standing groups (median of 237 s vs 64 s and 39 s, respectively; P < 0.001).
      CONCLUSION: Z-line visualization in patients undergoing SBCE can be accurately
      achieved in most cases when the capsule is swallowed in the right supine
      position.

PMID- 20039452
TI  - Incidental findings at MRI-enterography in patients with suspected or known
      Crohn's disease.
AB  - AIM: To determine the frequency and clinical impact of incidental findings
      detected with magnetic resonance imaging (MRI)-enterography in patients with
      suspected or known Crohn's disease (CD). METHODS: Incidental findings were
      defined as unexpected lesions outside the small intestine, not previously known
      or suspected at the time of referral, and not related to inflammatory bowel
      disease. Through a systematic review of medical charts we analyzed the clinical
      impact of incidental findings, and compared the MRI findings with subsequent
      diagnostic procedures. RESULTS: A total of 283 patients were included in the
      analysis, and MRI detected active CD in 31%, fistula in 1.4% and abscess in 0.7%.
      Extra-intestinal findings not related to CD were recorded in 72 patients (25%),
      of which 58 patients (20%) had 74 previously unknown lesions. Important or
      incompletely characterized findings were detected in 17 patients (6.0%).
      Incidental findings led to 12 further interventions in 9 patients (3.2%)
      revealing previously unknown pathological conditions in 5 (1.8%). One patient
      (0.4%) underwent surgery and one patient was diagnosed with a malignant disease.
      MRI detected incidental colonic lesions in 16 patients of which additional work
      up in 4 revealed normal anatomy. Two patients (0.7%) benefitted from the
      additional examinations, whereas incidental findings led to unnecessary
      examinations in 9 (3.2%). CONCLUSION: In a minority of patients with suspected or
      known CD, important incidental findings are diagnosed at MRI-enterography.
      However, a substantial number of patients experience unnecessary morbidity
      because of additional examinations of benign or normal conditions.

PMID- 20039453
TI  - Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori
      infection.
AB  - AIM: To study the association between Helicobacter pylori (H. pylori) infection
      and autoimmune type atrophic gastritis. METHODS: Twenty-three patients with
      different grades of atrophic gastritis were analysed using enzyme immunoassay
      based serology, immunoblot-based serology, and histology to reveal a past or a
      present H. pylori infection. In addition, serum markers for gastric atrophy
      (pepsinogen I, pepsinogen I/II and gastrin) and autoimmunity [parietal cell
      antibodies (PCA), and intrinsic factor (IF), antibodies] were determined.
      RESULTS: Of the 14 patients with severe gastric atrophy, as demonstrated by
      histology and serum markers, and no evidence for an ongoing H. pylori infection,
      eight showed H. pylori antibodies by immunoblotting. All eight had elevated PCA
      and 4/8 also had IF antibodies. Of the six immunoblot-negative patients with
      severe corpus atrophy, PCA and IF antibodies were detected in four. Among the
      patients with low to moderate grade atrophic gastritis (all except one with an
      ongoing H. pylori infection), serum markers for gastric atrophy and autoimmunity
      were seldom detected. However, one H. pylori negative patient with mild atrophic
      gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune
      gastritis. CONCLUSION: Signs of H. pylori infection in autoimmune gastritis, and
      positive autoimmune serum markers in H. pylori gastritis suggest an etiological
      role for H. pylori in autoimmune gastritis.

PMID- 20039454
TI  - On-treatment predictions of success in peg-interferon/ribavirin treatment using a
      novel formula.
AB  - AIM: To predict treatment success using only simple clinical data from peg
      interferon plus ribavirin therapy for chronic hepatitis C. METHODS: We analyzed
      the clinical data of 176 patients with chronic hepatitis and hepatitis C virus
      genotype 1 who received 48 wk standard therapy, derived a predictive formula to
      assess a sustained virological response of the individual patient using a
      logistic regression model and confirmed the validity of this formula. The formula
      was constructed using data from the first 100 patients enrolled and validated
      using data from the remaining 76 patients. RESULTS: Sustained virological
      response was obtained in 83 (47.2%) of the patients and we derived formulae to
      predict sustained virological response at pretreatment and weeks 4, 12 and 24.
      The likelihood of sustained virological response could be predicted effectively
      by the formulae at weeks 4, 12 and 24 (the area under the curve of the receiver
      operating characteristic: 0.821, 0.802, and 0.891, respectively), but not at
      baseline (0.570). The formula at week 48 was also constructed and validation by
      test data achieved good prediction with 0.871 of the area under the curve of the
      receiver operating characteristic. Prediction by this formula was always superior
      to that by viral kinetics. CONCLUSION: These results suggested that our formula
      combined with viral kinetics provides a clear direction of therapy for each
      patient and enables the best tailored treatment.

PMID- 20039455
TI  - Reoperation for early postoperative complications after gastric cancer surgery in
      a Chinese hospital.
AB  - AIM: To investigate the occurrence of postoperative complications of gastric
      cancer surgery, and analyze the potential causes of reoperation for early
      postoperative complications. METHODS: A total of 1639 patients who underwent
      radical or palliative gastrectomies for gastric cancer were included in the
      study. The study endpoint was the analysis of postoperative complications in
      inpatients. RESULTS: About 31% of patients had early postoperative complications,
      and complications of infection occurred most frequently. Intra-abdominal
      hemorrhage and anastomotic leak were the main causes of reoperation, which
      accounted for about 2.2%. Mortality was 11.1% in the reoperation group, but was
      only 0.8% in other patients. The duration of postoperative stay in hospital was
      significantly longer and the total expenditure was markedly higher in the
      patients who underwent reoperation (P < 0.001). There was no significant
      association of any available factors in this study with the high rate of
      reoperation. CONCLUSION: Reoperation significantly increases the mortality rate
      and raises the burden of the surgical unit. More prospective studies are required
      to explore the potential risk factors.

PMID- 20039456
TI  - Electro-acupuncture to prevent prolonged postoperative ileus: a randomized
      clinical trial.
AB  - AIM: To examine whether acupuncture can prevent prolonged postoperative ileus
      (PPOI) after intraperitoneal surgery for colon cancer. METHODS: Ninety patients
      were recruited from the Fudan University Cancer Hospital, Shanghai, China. After
      surgery, patients were randomized to receive acupuncture (once daily, starting on
      postoperative day 1, for up to six consecutive days) or usual care. PPOI was
      defined as an inability to pass flatus or have a bowel movement by 96 h after
      surgery. The main outcomes were time to first flatus, time to first bowel
      movement, and electrogastroenterography. Secondary outcomes were quality of life
      (QOL) measures, including pain, nausea, insomnia, abdominal distension/fullness,
      and sense of well-being. RESULTS: No significant differences in PPOI on day 4 (P
      = 0.71) or QOL measures were found between the groups. There were also no group
      differences when the data were analyzed by examining those whose PPOI had
      resolved by day 5 (P = 0.69) or day 6 (P = 0.88). No adverse events related to
      acupuncture were reported. CONCLUSION: Acupuncture did not prevent PPOI and was
      not useful for treating PPOI once it had developed in this population.

PMID- 20039457
TI  - Silencing Fas-associated phosphatase 1 expression enhances efficiency of
      chemotherapy for colon carcinoma with oxaliplatin.
AB  - AIM: To investigate whether silencing Fas-associated phosphatase 1 (FAP-1)
      expression enhances the efficiency of chemotherapy for colon carcinoma with
      oxaliplatin. METHODS: Expression of FAP-1 in mRNA and protein was detected by
      reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry.
      Small interfering RNA (siRNA) was designed according to the FAP-1 mRNA sequence.
      Cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay.
      Anenxin V- and propidine iodine (PI) were assayed by flow cytometry for the
      detection of apoptosis. RESULTS: The expression of FAP-1 was increased in SW480
      cells after chemotherapy with oxaliplatin. Transfection of FAP-1 siRNA into SW480
      cells silenced the expression of FAP-1 and consequently abolished the inhibitory
      function of Fas/FasL-mediated apoptosis pathway, thus increasing the efficacy of
      chemotherapy for colon carcinoma with oxaliplatin. CONCLUSION: RNA interference
      combined with conventional chemotherapy is more effective against colon cancer.

PMID- 20039458
TI  - Malignant schwannoma of the pancreas involving transversal colon treated with en
      bloc resection.
AB  - Pancreatic schwannoma is a very uncommon tumor of the pancreas, with only 27
      cases reported. Most pancreatic schwannomas are benign, with only four malignant
      tumors reported. We describe a case of giant malignant schwannoma of the
      pancreatic body and tail, which involved the transverse colon. The tumor was
      treated successfully with en bloc distal splenopancreatectomy and colon
      resection. This is believed to be the first reported radical operation for
      malignant schwannoma of the pancreatic body, with infiltration of the transverse
      colon, with excellent long-term results. The patient is alive and well 28 mo
      after the operation. The authors conclude that pancreatic schwannomas should be
      considered in the differential diagnosis of cystic neoplasms of the pancreas,
      although the diagnosis can only be confirmed by microscopic examination. In the
      case of the benign tumors, local excision is adequate, but in the case of
      malignant schwannoma, oncological standards must be fulfilled.

PMID- 20039459
TI  - Successful endoscopic sclerotherapy for cholecystojejunostomy variceal bleeding
      in a patient with pancreatic head cancer.
AB  - Variceal bleeding outside the esophagus and stomach is rare but important because
      of its difficult diagnosis and treatment. Bleeding from cholecystojejunostomy
      varices has been reported to be a late complication of palliative biliary surgery
      for chronic pancreatitis. Such ectopic variceal bleeding has never been reported
      after palliative surgery for pancreatic cancer, probably because of the limited
      lifespan of these patients. Herein, we report our successful experience using
      endoscopic cyanoacrylate sclerotherapy to treat bleeding from
      cholecystojejunostomy varices in a 57-year-old man with pancreatic head cancer.
      To our knowledge, this is the first case report in the literature of this rare
      complication.

PMID- 20039460
TI  - Ileum perforation due to delayed operation in obturator hernia: a case report and
      review of literatures.
AB  - A 83-year-old woman was admitted to our hospital because of intermittent
      abdominal colicky pain and vomiting for 26 h. The pain localized over the
      periumbilical area with radiation along the medial side of the thigh. Computed
      tomography scan with three-dimensional reconstruction revealed a loop of small
      bowel protruding into the left obturator canal. Incarcerated obturator hernia was
      diagnosed and emergency laparotomy was arranged immediately. Unfortunately, her
      family refused surgery because of her worsening condition. On the third evening
      after admission, the patient developed peritonitis and sepsis. Perforation of
      small bowel due to the incarceration was noted during laparotomy. Bowel resection
      and an end-ileostomy were performed. She recovered well despite of the
      complication of multiple organ dysfunction syndrome. Literature is reviewed, and
      the pathogenesis, clinical manifestation, imaging features and treatment are
      discussed.

PMID- 20039461
TI  - Biliary cystadenocarcinoma diagnosed with real-time contrast-enhanced
      ultrasonography: report of a case with diagnostic features.
AB  - Biliary cystadenocarcinoma is a very rare malignant cystic tumor of the liver,
      which is often misdiagnosed due to a poor recognition of it. We report a case of
      a 60-year-old man with biliary cystadenocarcinoma with his real time contrast
      enhanced ultrasound (CEUS) characteristics compared to those of computed
      tomography (CT) and magnetic resonance imaging (MRI), which were correlated with
      the surgical and pathologic findings. Cystic wall enhancement, internal
      septations and intra-cystic solid portions in the arterial phase were observed on
      CEUS after contrast agent injection. The enhancement was washed out progressively
      and depicted as hypo-enhancement in the portal and late phases. CT revealed a
      large irregular cystic lesion in the left liver lobe with no clear septations and
      solid components. MRI showed an irregular cystic occupying lesion with
      septations.

PMID- 20039462
TI  - A dynamic model of once-daily 5-aminosalicylic acid predicts clinical efficacy.
AB  - New once daily mesalamine formulations may improve adherence to medication usage.
      Response to Asacol and other forms of 5-aminosalicyclic acid (5-ASA) is better
      correlated with tissue concentrations and best predicted by concentrations of the
      drug within the lumen of the colon. Our group used computer simulation to predict
      colonic 5-ASA levels after Asacol administration. In our study, the model
      simulated Asacol distribution in the healthy colon, and during quiescent and
      active ulcerative colitis. An Asacol dosage of 800 mg, three times a day, was
      compared to 2400 mg given once a day. Under ideal conditions, the predicted
      maximum drug in the total colon and individual colonic segments over 100 d
      differed by less than 3% between single and multiple doses. Despite changes in
      motility and defection rates, the predicted maximum and average 5-ASA
      concentrations in the total colon and individual colonic segments differed by
      less than 10% between dosing regimens. Asymmetric distribution of 5-ASA in the
      colon was influenced by frequency of bowel movements and colonic transit rate. In
      active colitis, sigmoid 5-ASA concentration becomes negligible. Our model
      supports once daily administration of Asacol as standard treatment for ulcerative
      colitis.

PMID- 20039463
TI  - Modeling of glutamate-induced dynamical patterns.
AB  - Based on established physiological mechanisms, the paper presents a detailed
      computer model, which supports the hypothesis that temporal lobe epilepsy may be
      caused by failure of glutamate reuptake from the extracellular space. The
      elevated glutamate concentration causes an increased activation of NMDA receptors
      in pyramidal neurons, which in turn leads to neuronal dynamics that is
      qualitatively identical to epileptiform activity. We identify by chaos analysis a
      surprising possibility that muscarinergic receptors can help the system out of a
      chaotic regime.

PMID- 20039464
TI  - Mathematical study on ionic mechanism of lamprey central pattern generator model.
AB  - This paper studies the mechanisms of ionic channels in neurons of lamprey central
      pattern generator (CPG), such as the N-methyl-D-aspartate (NMDA) receptor channel
      and the calcium-dependent potassium channel etc. The CPG properties on
      oscillation attributed to the ionic mechanisms are exploited. The conditions for
      oscillation, divergence, convergence and the guidelines on selection of the
      parameters are established. The effects of key parameters on CPG frequency and
      duty cycle are investigated. Mathematical analysis and simulation study is
      performed to verify these results. This study will potentially enhance the
      effective application of biological CPG model into engineering practice such as
      robotics.

PMID- 20039465
TI  - Impossibility of asymptotic synchronization for pulse-coupled oscillators with
      delayed excitatory coupling.
AB  - Fireflies, as one of the most spectacular examples of synchronization in nature,
      have been investigated widely. In 1990, Mirollo and Strogatz proposed a pulse
      coupled oscillator model to explain the synchronization of South East Asian
      fireflies (Pteroptyx malaccae). However, transmission delays were not considered
      in their model. In fact, when transmission delays are introduced, the dynamic
      behaviors of pulse-coupled networks change a lot. In this paper, pulse-coupled
      oscillator networks with delayed excitatory coupling are studied. A concept of
      synchronization, named weak asymptotic synchronization, which is weaker than
      asymptotic synchronization, is proposed. We prove that for pulse-coupled
      oscillator networks with delayed excitatory coupling, weak asymptotic
      synchronization cannot occur.

PMID- 20039466
TI  - Faster training using fusion of activation functions for feed forward neural
      networks.
AB  - Multilayer feed-forward neural networks are widely used based on minimization of
      an error function. Back propagation (BP) is a famous training method used in the
      multilayer networks but it often suffers from the drawback of slow convergence.
      To make the learning faster, we propose 'Fusion of Activation Functions' (FAF) in
      which different conventional activation functions (AFs) are combined to compute
      final activation. This has not been studied extensively yet. One of the sub goals
      of the paper is to check the role of linear AFs in combination. We investigate
      whether FAF can enable the learning to be faster. Validity of the proposed method
      is examined by performing simulations on challenging nine real benchmark
      classification and time series prediction problems. The FAF has been applied to 2
      bit, 3-bit and 4-bit parity, the breast cancer, Diabetes, Heart disease, Iris,
      wine, Glass and Soybean classification problems. The algorithm is also tested
      with Mackey-Glass chaotic time series prediction problem. The algorithm is shown
      to work better than other AFs used independently in BP such as sigmoid (SIG),
      arctangent (ATAN), logarithmic (LOG).

PMID- 20039467
TI  - Global exponential stability of fuzzy interval delayed neural networks with
      impulses on time scales.
AB  - In this paper, we investigate the existence and uniqueness of equilibrium point
      for fuzzy interval delayed neural networks with impulses on time scales. And we
      give the criteria of the global exponential stability of the unique equilibrium
      point for the neural networks under consideration using Lyapunov method. Finally,
      we present an example to illustrate that our results are effective.

PMID- 20039468
TI  - No-reference video quality measurement with support vector regression.
AB  - A novel approach for no-reference video quality measurement is proposed in this
      paper. Firstly, various feature extraction methods are used to quantify the
      quality of videos. Then, a support vector regression model is trained and adopted
      to predict unseen samples. Six different regression models are compared with the
      support vector regression model. The experimental results indicate that the
      combination of different video quality features with a support vector regression
      model can outperform other methods for no-reference video quality measurement
      significantly.

PMID- 20039469
TI  - Chaos-based mixed signal implementation of spiking neurons.
AB  - A new design of Spiking Neural Networks is proposed and fabricated using a 0.35
      microm CMOS technology. The architecture is based on the use of both digital and
      analog circuitry. The digital circuitry is dedicated to the inter-neuron
      communication while the analog part implements the internal non-linear behavior
      associated to spiking neurons. The main advantages of the proposed system are the
      small area of integration with respect to digital solutions, its implementation
      using a standard CMOS process only and the reliability of the inter-neuron
      communication.

PMID- 20039470
TI  - An intelligent load shedding scheme using neural networks and neuro-fuzzy.
AB  - Load shedding is some of the essential requirement for maintaining security of
      modern power systems, particularly in competitive energy markets. This paper
      proposes an intelligent scheme for fast and accurate load shedding using neural
      networks for predicting the possible loss of load at the early stage and neuro
      fuzzy for determining the amount of load shed in order to avoid a cascading
      outage. A large scale electrical power system has been considered to validate the
      performance of the proposed technique in determining the amount of load shed. The
      proposed techniques can provide tools for improving the reliability and
      continuity of power supply. This was confirmed by the results obtained in this
      research of which sample results are given in this paper.

PMID- 20039471
TI  - Only a subset of Met-activated pathways are required to sustain oncogene
      addiction.
AB  - Tumor onset and progression require the accumulation of many genetic and
      epigenetic lesions. In some cases, however, cancer cells rely on only one of
      these lesions to maintain their malignant properties, and this dependence results
      in tumor regression upon oncogene inactivation ("oncogene addiction").
      Determining which nodes of the many networks operative in the transformed
      phenotype specifically mediate this response to oncogene neutralization is
      crucial to identifying the vulnerabilities of cancer. Using the Met receptor as
      the major model system, we combined multiplex phosphoproteomics, genome-wide
      expression profiling, and functional assays in various cancer cells addicted to
      oncogenic receptor tyrosine kinases. We found that Met blockade affected a
      limited subset of Met downstream signals: Little or no effect was observed for
      several pathways downstream of Met; instead, only a restricted and pathway
      specific signature of transducers and transcriptional effectors downstream of Ras
      or phosphoinositide 3-kinase (PI3K) was inactivated. An analogous signature was
      also generated by inhibition of epidermal growth factor receptor in a different
      cellular context, suggesting a stereotyped response that likely is independent of
      receptor type or tissue origin. Biologically, Met inhibition led to cell-cycle
      arrest. Inhibition of Ras-dependent signals and PI3K-dependent signals also
      resulted in cell-cycle arrest, whereas cells in which Met was inhibited
      proliferated when Ras or PI3K signaling was active. These findings uncover
      "dominant" and "recessive" nodes among the numerous oncogenic networks regulated
      by receptor tyrosine kinases and active in cancer, with the Ras and PI3K pathways
      as determinants of therapeutic response.

PMID- 20039472
TI  - [A survey of the past forty years' development in medical research in Hong Kong].

PMID- 20039473
TI  - [Research using the rolls of foreign citizens in the Medical Relief Corps
      (Chinese Red Cross) who were medical aid personnel in China during the Sino
      Japanese conflict].

PMID- 20039475
TI  - Nature Reviews Immunology. From the editors.

PMID- 20039476
TI  - How did our complex immune system evolve?

PMID- 20039477
TI  - Building national identity through ethnicity: ethnology in wartime Japan and
      after.

PMID- 20039478
TI  - Deviance and Docial Darwinism in Edogawa Ranpo's erotic-grotesque thriller Koto
      no Oni.

PMID- 20039479
TI  - Regional diversity in demographic and family patterns in preindustrial Japan.

PMID- 20039480
TI  - [Physicians and monsters: science as transgression in Dr. Faustus, Frankenstein,
      and Dr. Jekyll and Mr. Hyde].

PMID- 20039481
TI  - Leftist political mobilization, gender and identity: a case study of Kurdish
      Alevi migrants in Istanbul.

PMID- 20039482
TI  - Mahmudi order and clan, 1500-1606.

PMID- 20039484
TI  - From relief to mutual obligation: welfare rationalities and unemployment in 20th
      century Australia.

PMID- 20039485
TI  - Educational attainment of the children of divorce: Australia, 1940-90.

PMID- 20039486
TI  - Persecution: the Vietnamese paradigm.

PMID- 20039487
TI  - Transformation of colonial criminal law in early 19th-century Bengal: discursive
      formations.

PMID- 20039488
TI  - American Academy of Pediatric Dentistry reference manual 2009-2010.

PMID- 20039489
TI  - Abstracts of the American College of Surgeons 94th Annual Clinical Congress and
      the 64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical
      Problems, 11-15 October 2009, Chicago, Illinois, USA.

PMID- 20039490
TI  - Health care reform: radiology in the next decade.

PMID- 20039491
TI  - A note on homosexuality in porfirian and postrevolutionary northern Mexico.

PMID- 20039492
TI  - All night at the owl: the social and political relations of Mexicali's red-light
      district, 1913-1925.

PMID- 20039493
TI  - Anticipating the colonias: popular housing in El Paso and Ciudad Juarez, 1890
      1923.

PMID- 20039494
TI  - Sex, lies, and Victorians: the case of Newman Hall's divorce.

PMID- 20039495
TI  - The refugee experience: understanding the dynamics of refugee repatriation in
      Eritrea.

PMID- 20039496
TI  - The "globalization" of disease? India and the plague.

PMID- 20039497
TI  - From rapid change to stasis: official responses to cholera in British-ruled India
      and Egypt, 1860-1921.

PMID- 20039498
TI  - Diastolic heart failure: a clinical challenge early recognition & timely
      intervention is the need of the hour.
AB  - Diastolic Heart failure (DHF) is the major cause of morbidity and mortality all
      over the world. It is responsible for more than 50% of the heart failure cases.
      New onset of symptomatic DHF is a lethal disease with a 5-yr mortality of
      approximately 50%. DHF is also referred to as heart failure (HF) with normal left
      ventricular ejection fraction (LVEF)-HFNLVEF. The diagnosis of DHF requires the
      following criteria: (i) signs and symptoms of heart failure (ii) normal or mildly
      abnormal systolic left ventricular (LV) function (iii) evidence of LV diastolic
      dysfunction. Diagnostic evidence of LV diastolic dysfunction can be obtained
      invasively (LV end-diastolic pressure > 16 mmHg or mean pulmonary capillary wedge
      pressure > 12 mmHg) or non-invasively by tissue Doppler imaging (TDI) (E/E' >
      15). If TDI yields an E/E' ratio suggestive of LV diastolic dysfunction (15 >
      E/E' > 8), then additional echo variables are required for diagnostic evidence of
      LV diastolic dysfunction, which include Doppler flow profile of mitral valve or
      pulmonary veins, measurement of LV mass index (LVMi) or left atrium volume index
      (LAVi), electrocardiographic evidence of atrial fibrillation or high levels of B
      natreuretic peptide. Echo-Doppler techniques using LV filling pressures and
      tissue Doppler imaging of the mitral annulus help in identifying and classifying
      the degree of LV diastolic dysfunction. However, clinically this is more relevant
      to advanced overt disease. Therefore early recognition of DHF in relatively
      asymptomatic or less symptomatic patients with occult LV diastolic dysfunction is
      a real challenge. Recently it has been shown that reduction in left atrial strain
      and strain rate and increase in left atrial (LA) stiffness index has a high
      predictive value for detection of occult LV diastolic dysfunction. Thus early
      recognition of occult DHF and timely therapeutic intervention may help in
      prognostic stratification in DHF.

PMID- 20039499
TI  - Real-time three-dimensional echocardiography: a current view of what
      echocardiography can provide?
AB  - The development of real-time three dimensional echocardiography has allowed for
      the incorporation of 3-dimensional echocardiographic imaging into everyday
      cardiovascular clinical practice. In this State of the Art Paper we will provide
      an overview of three dimensional echocardiography and specific indications in
      which it has incremental value over traditional 2-dimensional echocardiography.

PMID- 20039500
TI  - Plasma homocysteine in obese, overweight and normal weight hypertensives and
      normotensives.
AB  - AIM: The aim of the present study was to assess the interrelationship of obesity
      with plasma homocysteine levels as well as vitamin B12 and folic acid levels in
      hypertensive and normotensive subjects. METHODS: Sixty-five hypertensive and
      sixty-five normotensive patients were studied. Plasma homocysteine, vitamin B12
      and folic acid, lipid parameters, blood pressure, pulse pressure levels, body
      mass index were estimated in all the subjects. RESULTS: We observed raised
      prevalence of hyperhomocysteinemia, dyslipidemia and reduced vitamin levels among
      the hypertensives compared to normotensives. We observed, among the overweight
      and obese hypertensives, significantly raised plasma homocysteine, reduced
      vitamin B12 and folic acid levels, raised blood pressure (systolic and
      diastolic), pulse pressure, and severe dyslipidemia compared to normal weight
      hypertensives. Also, among the overweight and obese normotensives, we observed
      significantly raised plasma homocysteine, along with reduced vitamin B12 and
      folic acid levels compared to normal weight normotensives. Even the blood
      pressure levels were in higher normal range in obese and overweight normotensives
      compared to normal weight normotensives. Among the hypertensives, homocysteine
      was positively correlated significantly with obesity and arterial pressure
      levels; and negatively correlated with vitamin levels. Thus, a raise in BMI was
      associated with elevated homocysteine and reduced vitamin levels among
      hypertensives. CONCLUSIONS: Our data points to significant interrelationship
      between homocysteine, hypertension and obesity.

PMID- 20039501
TI  - Transcoronary pacing: are the modern wires effective?
AB  - AIMS/OBJECTIVE: Coronary guide wires can be used for pacing the left ventricle
      during coronary angioplasty, however the experience with modern coronary guide
      wires as pacing wires is limited. The aim of this study was to determine the
      safety and efficacy of currently used coronary guide wires for transcoronary
      pacing. METHODS AND RESULTS: Transcoronary pacing was tested in 25 patients who
      were scheduled to undergo elective coronary angioplasty. Four different coronary
      guide wires were tested using an adaptive alligator clip connecting the guide
      wire to the pulse generator. Resistance of various guide wires was also measured
      ex vivo at 150, 175 and 190 cms from the tip respectively. BMW and Galeo wires
      were used in 12 and 11 patients respectively while Couger and Magic wire were
      used in one patient each. Pacing was successful in all patients with no pacing
      related complication. Most patients had unifocal ventricular ectopics. Mean
      threshold varied between 4 mA to 5.54 mA. Resistance varied from 12 ohms to 31
      ohms depending upon the wire and distance from the tip. CONCLUSION: Transcoronary
      pacing using modern coronary guide wires appears to be dependable, well tolerated
      and safe temporary measure for significant bradyarrhythmias.

PMID- 20039502
TI  - The thoracic veins and ablation for atrial fibrillation.
AB  - The last decade has witnessed a revolution in the management of paroxysmal atrial
      fibrillation (PAF). Fundamental to these changes has been the understanding that
      the thoracic veins, which include the pulmonary veins and superior vena cava,
      represent the initiating trigger site for atrialf ibrillation (AF). In this
      article, we discuss the rationale for ablation around the thoracic veins for
      managing patients with PAF. We describe a selection of appropriate patients for
      venous isolation procedures, particularly in the context of the Indian
      subcontinent and then go on to explain ablation approaches that optimize safety
      and efficacy with the complex procedures. Although this article is targeted for
      interventional electrophysiologists beginning these procedures the rational,
      initial patient selection for referral and follow up of post ablation patients
      will be relevant to all practicing cardiologists.

PMID- 20039504
TI  - Curriculum in cath lab: coronary hardware--Part II. Guidewire selection for
      coronary angioplasty.

PMID- 20039503
TI  - Dual antiplatelet therapy in ACS: time-dependent variability in platelet
      aggregation during the first week.
AB  - AIMS AND OBJECTIVES: Platelets play an important role in the pathogenesis of
      Acute Coronary Syndrome (ACS). Most of the complications of ACS occur during the
      initial hours of presentation. We tried to gain an insight into the platelet
      function during the initial phase of ACS in patients on dual antiplatelet
      therapy. MATERIALS AND METHODS: Platelet aggregation study was performed by light
      transmittance aggregometry in 64 ACS patients 48 hour and 7 days after initiation
      of dual antiplatelet therapy with aspirin and clopidogrel. RESULTS: Epinephrine,
      ADP and collagen induced platelet aggregation was significantly higher at 48
      hours, following initiation of dual antiplatelet therapy, in comparison to the
      profile observed on the 7th day. Diabetics demonstrated a significantly higher
      aggregation at both the time points and aggregation was also somewhat higher in
      smokers though it did not reach statistical significance. CONCLUSION: This study
      conceptualizes the hypothetical role of alpha-2 adrenoreceptor blockers during
      the early hours following ACS and also warrants further investigations exploring
      the optimum loading dose of antiplatelet agents, especially clopidogrel in
      patients with ACS.

PMID- 20039505
TI  - Revascularization of left main bifurcation lesions by "Mini-Crush technique" in a
      subject on haemodialysis.
AB  - A 75 old diabetic, hypertensive subject with chronic kidney disease stage V (on
      haemodialysis) had Acute Coronary Syndrome. Coronary angiography revealed
      bifurcation lesion of the distal Left Main Coronary Artery involving the origins
      of LAD & LCx, CABG was denied because of comorbidites, old age and unwillingness
      of the patient to face the risk of surgery. The LM bifurcation was treated in
      "Mini-Crush technique" resulting in TIMI-III flow and there was uneventful post
      interventional recovery without MACE.

PMID- 20039506
TI  - Coronary artery spasm as a cause of chest pain and re-elevation of ST segment and
      cardiogenic shock after PTCA.
AB  - We describe a case that underwent successful percutaneous transluminal coronary
      angioplasty in cardiogenic shock but after half an hour, again had severe chest
      pain with re-elevation of ST segment and was found to have coronary artery spasm
      as a cause of recurrence of symptoms.

PMID- 20039507
TI  - STEMI interventions--a review of relevant clinical trials.
AB  - Major advances have been made in primary reperfusion and adjunctive therapies for
      STEMI. Mechanical reperfusion therapy has become the preferred reperfusion
      strategy for patients with STEMI. Outcomes have improved with the use of stents,
      platelet inhibitors, and with increased experience, and there is a promise that
      outcomes can become even better with new methods to enhance myocardial
      reperfusion and reduce reperfusion injury and with new anticoagulants and drug
      eluting stents. Recent trends from the NRMI have shown that the frequency of use
      of primary PCI has increased and has surpassed lytic therapy, but primary PCI is
      used to treat only a minority of patients with STEMI. The major challenge for
      clinicians in the next decade will be to find new ways to make mechanical
      reperfusion more available, improve outcomes through the use of optimal adjuvant
      therapies and improved systems of care to speed primary PCI. The nation-wide
      effort to reduce door-to-balloon times has been launched by American Heart
      Association, with goal of making primary PCI more available to patients with
      STEMI.

PMID- 20039508
TI  - ECG of the month. Vignettes in electrocardiography: exploring initial QRS forces-
      a diagnostic clue to wide QRS tachycardia.

PMID- 20039509
TI  - Echo of the month. A child with cyanosis.

PMID- 20039510
TI  - Angio quiz. Intra-arterial hematoma after percutaneous coronary intervention of
      Shepard's Crook right coronary artery.

PMID- 20039511
TI  - Bilateral coronary to pulmonary artery fistulae--5 1/2 years of follow-up with
      conservative treatment.
AB  - Coronary artery fistulae are uncommon form of coronary anomalies, often diagnosed
      incidentally during coronary arteriography. Dual origin of fistulae from both
      coronary arteries draining into the pulmonary arterial branches is extremely rare
      and their natural history is unknown. In this report, we present a case of middle
      aged female with an incidental finding of bilateral coronary artery to pulmonary
      artery fistulae on coronary arteriography, which was followed clinically for 5
      1/2 years with conservative treatment, remaining in NYHA class I to II with no
      symptoms directly related to her coronary artery fistulae.

PMID- 20039512
TI  - Management of in-stent restenosis in a patient with a drug eluting stent on
      hemodialysis awaiting renal transplantation.
AB  - This brief report describes the dilemma of managing significant in-stent
      restenosis in a diabetic patient of end stage renal disease on regular
      hemodialysis awaiting renal transplantation within a paclitaxel eluting stent in
      his proximal left anterior descending artery with moderately impaired left
      ventricle systolic dysfunction. In view of the imminent renal transplantation
      procedure the patient underwent percutaneous coronary intervention with a cobalt
      chromium bare metal stent and was subsequently taken up for successful renal
      transplantation after 6 weeks with temporary discontinuation of antiplatelet
      therapy.

PMID- 20039513
TI  - Life threatening protamine reaction during bypass surgery--a case report.
AB  - An anaphylactic reaction to protamine sulphate during cardiac surgery is a rare
      but known entity. Preoperative prediction and outcome of such a reaction is still
      unclear. We report a case of severe anaphylactic reaction to protamine sulphate
      in a diabetic while performing beating heart bypass surgery. We also reviewed the
      literature and discussed the management of such cases.

PMID- 20039514
TI  - Echocardiography for assessment of electromechanical dyssynchrony.

PMID- 20039515
TI  - Alert: the dark side of chats--internet without boundaries.
AB  - The web has some unique advantages: It eliminates barriers of space and time;
      information flows quicker and is more accessible to all; the markets are more
      effective; community and interpersonal communication is more evolved. However,
      the web is also anonymous, without supervision, freedom of speech is exploited,
      minors and other web users are exploited, racism and prejudice are encouraged.
      These manifestations of violence not only hurt many people but actually pose a
      threat to the existence of the web as a place for exchanging ideas and thoughts,
      as a tool for relaying messages in a liberal and democratic fashion. Today, it is
      not legally possible to stop any discussion group or chats, like the one in which
      Eran participated, which develop dialogues regarding death or suicide. A wise and
      proper use of the web will be achieved by agreements and not enforcement. It is a
      process of education in its widest meaning that will be accomplished through the
      acceptance of norms. Proper use of the web will be possible when all sides-
      users, site owners and suppliers--willingly commit to values of mutual respect,
      decency and protection of individual fundamental rights to freedom. The web,
      which is a great blessing to the communication between people, organizations and
      cultures, carries with it substantial risks, especially to young users. The rapid
      expansion of the web and the increase in the number of users has brought many
      social-ideological dangers alongside the many advantages. In order to deal with
      these issues, a few years ago I initiated an association known as Eshnav
      (www.eshnav.org.il) which acts to increase public awareness to the risks and
      dangers of the web. Eshnav's mission, established to commemorate Eran's memory,
      is to promote public awareness to the positive and negative aspects of using the
      web on society and its values, and to promote the wise and safe use of the web.
      Eran was in great distress and needed empathy, encouragement and support. Sadly,
      when his mind was filled with suicidal thoughts he stumbled upon a group on the
      web that embraced the culture of death and suicide discussions. In his darkest
      moments, when he was on the verge of an abyss, he was probably pushed by these
      discussions into his death, and he was only 19-years-old. When Eshnav was created
      we saw the dangers of an Internet with no boundaries, a place where this
      remarkable technology was grossly misused. This is from the association's
      statement: "In a world without fences and boundaries clearer rules of conduct are
      needed." We emphasized that "the web is like a new world that has yet to
      determine its own boundaries. As such, it poses new challenges, both moral and
      ideological, which cannot be met based on past experience as this phenomenon is
      still too new and uncharted. We must do the utmost to be vigil about making the
      Internet as safe as possible even when this new frontier is constantly shifting
      and evolving." Let us bow our heads in sadness in memory of Eran whose strength
      did not withstand the great distress he was in, and who let himself be dragged by
      the death culture and darkness on the web into an untimely grave. We shall find
      strength in our determination to create a responsible web community in which
      freedom of speech will not be abused to hurt the individual rights of each and
      every human being to life, respect, reputation and privacy.

PMID- 20039516
TI  - Commentary: Street lights on the dark side of the net.

PMID- 20039517
TI  - Psychiatric care in restricted conditions for work migrants, refugees and asylum
      seekers: experience of the Open Clinic for Work Migrants and Refugees, Israel
      2006.
AB  - In the last few decades, the State of Israel has become a target for work
      migrants, refugees, asylum seekers and victims of human trafficking, as part of
      the trend of world immigration. Immigration is a process of loss and change with
      significant socio-psychological stress, with possible effects on the immigrants'
      mental health. The Physicians for Human Rights - Israel (PHR) Association
      operates a psychiatric clinic as part of the Open Clinic for Work Migrants and
      Refugees. This article will present major clinical issues regarding psychiatry
      and immigration in Israel according to the data collected at the clinic. Trauma
      and stress-related psychopathology was found to have a high prevalence in
      immigrant patients treated at the clinic; prevalence of PTSD (post-traumatic
      stress disorder) in immigrants was high (23%) and even higher in refugees (33%).
      Female immigrants are at higher risk for psychiatric hospitalization. The
      relative rate of African patients at the clinic is significantly higher than
      patients from other continents. A significant association was found between
      psychiatric hospitalization and suicide attempts. Immigrant patients present a
      combination of psychiatric, socio-economic and general medical conditions, which
      demands a holistic view of the patient. The evaluation of an immigrant patient
      must take into account the stress related to immigration, gender, culture of
      origin and the risk for suicide and hospitalization. Treatment recommendations
      include awareness of cultural diversities, acquiring information regarding the
      pre-immigration history, preferably using cultural consultants with background in
      the immigrants' culture and community. Decision-making about medication and
      diagnostic evaluation should be as inexpensive as possible. Basic human needs
      (food, shelter) and family support should be included in the decisions about
      treatment.

PMID- 20039518
TI  - Use of age-adjusted rates of suicide in time series studies in Israel.
AB  - Durkheim's modified theory of suicide was examined to explore how consistent it
      was in predicting Israeli rates of suicide from 1965 to 1997 when using age
      adjusted rates rather than crude ones. In this time-series study, Israeli male
      and female rates of suicide increased and decreased, respectively, between 1965
      and 1997. Conforming to Durkheim's modified theory, the Israeli male rate of
      suicide was lower in years when rates of marriage and birth are higher, while
      rates of suicide are higher in years when rates of divorce are higher, the
      opposite to that of Israeli women. The corrected regression coefficients suggest
      that the Israeli female rate of suicide remained lower in years when rate of
      divorce is higher, again the opposite suggested by Durkheim's modified theory.
      These results may indicate that divorce affects the mental health of Israeli
      women as suggested by their lower rate of suicide. Perhaps the "multiple roles
      held by Israeli females creates suicidogenic stress" and divorce provides some
      sense of stress relief, mentally speaking. The results were not as consistent
      with predictions suggested by Durkheim's modified theory of suicide as were rates
      from the United States for the same period nor were they consistent with rates
      based on "crude" suicide data. Thus, using age-adjusted rates of suicide had an
      influence on the prediction of the Israeli rate of suicide during this period.

PMID- 20039519
TI  - Specific characteristics of suicide attempts in patients with schizophrenia in
      Turkey.
AB  - BACKGROUND: Suicide attempt is a universally observed human behavior related to
      bio-psychological, social and cultural factors. While some studies have suggested
      that specific demographic/cultural and clinical variables are associated with
      suicide attempts in schizophrenia, these associations are often inconsistent.
      OBJECTIVES: The aim of this study was to investigate the possible association
      between socio-demographic and clinical variables and suicidal behavior in a
      sample of patients diagnosed as having schizophrenia in Turkey. METHODS: Three
      hundred patients with a SCID-I diagnosis of schizophrenia were studied. The
      sample was subdivided into two groups based on the presence or absence of
      lifetime suicide attempts. The main demographic and clinical variables
      retrospectively collected were analyzed and compared between the two groups.
      RESULTS: The results of present study revealed that the subjects who had and had
      not attempted suicide did not differ with respect to demographic variables. The
      suicide attempters tend to have younger age at onset of disorder, longer duration
      of psychosis, more hospitalizations, are more likely to have lifetime major
      depressive episodes, and a significantly higher rate of alcohol abuse or
      dependence than patients without a lifetime history of suicide attempts.
      CONCLUSIONS: Consistent with the results of previous studies, it has been found
      that demographic variables may be less valuable predictors of suicidal behavior
      than clinical variables. These results lead to the idea that socio-cultural
      variations may not be a critical determinant for suicide attempt among patients
      with schizophrenia.

PMID- 20039520
TI  - Suicidal ideation in patients with schizophrenia.
AB  - OBJECTIVE: To evaluate the factors affecting suicidal ideas in patients with
      schizophrenia in terms of some socio-demographic and clinical properties. METHOD:
      The sample of the study consisted of 120 patients with schizophrenia selected
      from among patients receiving treatment at Trabzon Atakoy Psychiatry Hospital.
      All patients were evaluated using a Socio-demographic Data Collection Form,
      Reasons for Living Inventory (RLI), Calgary Depression Scale for Schizophrenia
      (CDSS), Positive and Negative Syndromes Scale (PANSS), and Structured Clinical
      Interview for DSM-IV Axis I Disorders (SCID-I). RESULTS: Of the patients, 31.6%
      had suicide ideation. Negative symptoms are found to be significantly higher. The
      group with suicidal ideation had fewer reasons for living than the group without.
      CONCLUSION: Evaluations of the history of suicide attempts, depression and
      hopelessness in patients with schizophrenia are thought to be important in the
      prevention of suicidal behavior in these patients.

PMID- 20039521
TI  - Personality dimensions in male patients with early-onset alcohol dependence who
      seek treatment.
AB  - AIMS: The aim of this study is to examine the capacity of different personality
      dimensions to predict early-onset alcoholism (EOA). METHODS: Participants were
      176 consecutively admitted male inpatient alcohol dependents. Patients were
      grouped as EOA (onset before age 25) and late onset alcoholism (LOA). RESULTS:
      Overall severity of psychopathology and alcohol dependence were higher in EOAs
      (51.1%) than LOAs, whereas self-directedness (SD) dimension of personality was
      lower in EOAs. Among the other personality dimensions only lower SD scores,
      together with lower current age predicted EOA. CONCLUSION: Present study suggests
      that it is important to take EOA into consideration while planning the treatment
      of alcohol dependency, because of their higher probability of having low SD
      scores, as well as higher severity of psychopathology and alcohol-related
      problems.

PMID- 20039522
TI  - Community emergency psychiatric service in Israel: a one-year experience.
AB  - BACKGROUND: In 2005 the Forensic Psychiatry Department of Mental Health Services
      at the Ministry of Health launched a pilot project: the Community Emergency
      Psychiatric Service (CEPS). The purpose was to offer community-based emergency
      response to acute psychiatric conditions during after-hours periods, including
      Saturdays and holidays. The project was implemented in the Tel Aviv, Central and
      Southern districts. METHOD: Advertisements were posted in mass circulating
      newspapers announcing the launching of the new program for the general public in
      the participating districts. The public was invited to call the hotline of the
      medical emergency service, Magen David Adom (MDA), in the event of psychiatric
      distress or emergency. MDA personnel were instructed to give the callers a
      telephone number of an on-call psychiatrist. The Ministry of Health engaged a
      pool of seven licensed psychiatrists to be available on-call one per shift. The
      psychiatrists offered crisis intervention over the phone or house visits when
      necessary. RESULTS: Data were obtained from the Tel Aviv, Central and Southern
      Districts. The results show that there were 1,472 calls between May 2005 and June
      2006. In 198 cases (13.5%) clients were referred for treatment and follow-up to
      local outpatient clinics, while in 116 of the cases (7.8%) a home visit by the on
      call psychiatrist was carried out, resulting in 50 voluntary and 16 involuntary
      hospitalizations. An examination of records of calls received by the on-call
      psychiatrists (N=97) during August 2006 suggests that most callers fit the
      following profile: female, ranging in age 19-35, unmarried, with diagnosis of
      schizophrenia, with no previous psychiatric hospitalizations, and presenting no
      danger to herself or others. CONCLUSIONS: A limited response team, comprised of
      one on-call psychiatrist per shift, can provide a viable service for psychiatric
      emergencies in a population center of approximately 2.7 million. The findings
      also suggest that such a service may increase the number of referrals to
      outpatient clinics in the community as well as the number of voluntary and
      involuntary hospitalizations after working hours. The potential contribution of
      such a project to improving accessibility to outpatient psychiatric care and to
      reinforcing continuity of care among in- and out-patient facilities needs further
      investigation as is the important question of cost-effectiveness.

PMID- 20039523
TI  - Effect of the selective norepinephrine reuptake inhibitor reboxetine on cognitive
      dysfunction in schizophrenia patients: an add-on, double-blind placebo-controlled
      study.
AB  - The noradrenergic (NE) system mediates cognitive dysfunction in schizophrenia
      patients, and the NE transporter represents a putative target for cognitive
      enhancing therapy. In a double-blind placebo-controlled study we evaluated the
      effect of add-on reboxetine (4 mg/day), a selective norepinephrine reuptake
      inhibitor (NRI), co-administered with atypical antipsychotic olanzapine (10
      mg/day) on cognitive functioning in DSM-IV schizophrenia patients. The Automated
      Neuropsychological Assessment Metrics battery and Wisconsin Card Sorting Test
      were used to assess selective cognitive functions at baseline and endpoint (6
      weeks). Clinical assessment was also performed. No between-group differences were
      found in neurocognitive tests, suggesting that reboxetine did not significantly
      change patients' cognitive performance compared to placebo. Reboxetine was well
      tolerated and did not interfere with the therapeutic effect of olanzapine. Long
      term studies using higher reboxetine dosages and alternative NRIs (e.g.,
      atomoxetine) are needed to determine the role of NRIs as cognitive enhancers in
      patients with schizophrenia and other disorders associated with cognitive
      impairments.

PMID- 20039524
TI  - Criminal and legal responsibilities in Tourette's syndrome.
AB  - Tourette's Syndrome (TS) is a neuropsychological disorder characterized by the
      presence of multiple involuntary motor tics accompanied by one or more vocal
      tics. Articles about TS and criminal responsibility and the restriction of civil
      rights are limited. A person with TS was evaluated to consider his criminal
      responsibility after swearing at a referee during a football game. He was also
      evaluated as to whether or not he was capable of professionally driving a service
      bus. Additionally, medico-legal situations regarding military service, obtaining
      a shotgun license and marriages of patients with TS were considered.

PMID- 20039525
TI  - Reducing mental illness stigma in mental health professionals using a web-based
      approach.
AB  - OBJECTIVE: This study was designed to investigate the efficacy of a web-based
      mental disorder stigma education program for mental health professionals.
      METHODS: The sample consisted of 205 individuals who were either residents or
      specialists in psychiatry. Participants were contacted through a national web
      based e-mail group that consisted of professionals in psychiatry, who were
      randomly assigned to experimental and control groups. The experimental group
      received an informative e-mail which contained a general account of "stigma"
      before they were asked to respond to an Internet-based questionnaire which was
      designed to predict their stigmatizing attitudes towards individuals with mental
      disorders. Control subjects, on the other hand, were asked to respond to the same
      Internet-based questionnaire without having been given the aforementioned
      informative e-mail. RESULTS: The experimental group, compared to the control
      group, demonstrated a lesser stigmatizing attitude towards individuals with
      mental illness, as measured by the Internet-based survey which utilized the
      "social distance" concepts of stigma. CONCLUSIONS: These data suggest that such
      "anti-stigma" campaigns using the potential of the Internet might be an effective
      tool in the fight against the stigmatization of persons with mental illness.

PMID- 20039526
TI  - Eating disorder symptoms improved by antireflux surgery: a case report with a six
      year follow up.
AB  - BACKGROUND: Anorexia nervosa (AN) is a chronic disorder that can overlap with
      lower esophageal sphincter failure and delayed gastric emptying. Patients with
      anorexia nervosa or other eating disorders may have a high incidence of
      gastrointestinal complaints, which can also be observed in gastroesophageal
      reflux disease (GERD). The overlap in the symptoms of these disorders may cause
      problems in differential diagnosis and treatment decisions. CASE DESCRIPTION: We
      report on a case of a patient with anorexia nervosa who did not benefit from
      conventional treatment strategies such as psychotropic drugs and psychotherapy,
      but remitted after antireflux surgery. CONCLUSION: When dealing with patients
      with symptoms of anorexia nervosa, physicians should keep in mind that these
      patients may have serious esophagogastric complications that can affect their
      response to psychiatric treatment. Alternatively, some patients with primary
      esophageal disorders may present with symptoms of eating disorders.

PMID- 20039527
TI  - Medicine, evolution, and natural selection: an historical overview.
AB  - Contemporary Darwinian medicine is a still-expanding new discipline, one of whose
      principal aims is to arrive at an evolutionary understanding of those aspects of
      the body that leave it vulnerable to disease. Historically, there was a precedent
      for this research; between 1880 and 1940, several scientists tried to develop
      some general evolutionary theories of disease as arising from deleterious traits
      that escape elimination by natural selection. In contrast, contemporary Darwinian
      medicine uses evolutionary theory to consider all the possible reasons why
      selection has left humans vulnerable to disease.

PMID- 20039528
TI  - The reticulating phylogeny of island biogeography theory.
AB  - Biogeographers study all patterns in the geographic variation of life, from the
      spatial variation in genetic and physiological characteristics of cells and
      individuals, to the diversity and dynamics of biological communities among
      continental biotas or across oceanic archipelagoes. The field of island
      biogeography, in particular, has provided some genuinely transformative insights
      for the biological sciences, especially ecology and evolutionary biology. Our
      purpose here is to review the historical development of island biogeography
      theory during the 20th century by identifying the common threads that run through
      four sets of contributions made during this period, including those by Eugene
      Gordon Munroe (1948, 1953), Edward O. Wilson (1959, 1961), Frank W. Preston
      (1962a,b), and the seminal collaborations between Wilson and Robert H. MacArthur
      (1963, 1967), which revolutionized the field and served as its paradigm for
      nearly four decades. This epistemological account not only reviews the intriguing
      history of island theory, but it also includes fundamental lessons for advancing
      science through transformative integrations. Indeed, as is likely the case with
      many disciplines, island theory advanced not as a simple accumulation of facts
      and an orderly succession of theories and paradigms, but rather in fits and
      starts through a reticulating phylogeny of ideas and alternating periods of
      specialization and reintegration. We conclude this review with a summary of the
      salient features of this scientific revolution in the contest of Kuhn's
      structure, which strongly influenced theoretical advances during this period, and
      we then describe some of the fundamental assumptions and tenets of an emerging
      reintegration of island biogeography theory.

PMID- 20039529
TI  - The relationship between grief adjustment and continuing bonds for parents who
      have lost a child.
AB  - This article presents findings from a study on the impact of a child's death on
      parents. We explored the prominence and adaptiveness of parents' continuing bonds
      expressions, psychological adjustment, and grief reactions. A qualitative case
      study methodology was used to describe six cases. Participants were classified
      into two groups based on scores on the Inventory of Complicated Grief.
      Commonalities in themes on the Continuing Bonds Interview and projective drawings
      were assessed. Those in the Non-Complicated Grief Group reported internalization
      of positive qualities and identification with the deceased child as a role model,
      whereas participants in the Complicated Grief Group did not report these
      experiences. In addition, the drawings of those in the Non-Complicated Grief
      Group were evaluated as more adaptive than those in the Complicated Grief Group.

PMID- 20039530
TI  - Dying to know: a community survey about dying and end-of-life care.
AB  - A community survey of Sioux Falls, South Dakota was conducted in 2004 to
      understand knowledge, attitudes, and preferences about end-of-life (EOL) care and
      to generate conversations about these topics. Questionnaires were sent to 5,000
      randomly selected households, with a return of 1,042 (21%). Most respondents said
      preparation for EOL is very important, yet far fewer had taken steps to ensure
      their EOL wishes would be known or met. These disparities are examined, with
      recommendations for future research and public policy. Bivariate analyses
      revealed significant differences by age, sex, education, marital status, and
      religiosity. Community studies are important for baseline understanding, evoking
      conversation, and setting goals for change. Public education is needed to
      strengthen understandings of hospice care, and professional education is needed
      to raise awareness about practitioners' roles in resolving discrepancies between
      what people want and what they get at end of life.

PMID- 20039531
TI  - The effect of health and penal harm on aging female prisoners' views of dying in
      prison.
AB  - With tougher sentencing laws, an increasing number of individuals are finding
      themselves spending their final years of life in prison. Drawing on a sample of
      327 women over the age of 50 incarcerated in five Southern states, the present
      study investigates the relationship between numerous health variables and the
      Templer Death Anxiety Scale (TDAS). Qualitatively, the article also provides
      personal accounts from inmates that serve to reinforce death fears when engaging
      the prison health care system. Participants reported a mean of 6.40 on the TDAS
      indicating a substantial degree of death anxiety when compared to community
      samples. Both mental and physical health measures were important indicators of
      death anxiety. Qualitative information discovered that respondents' concerns
      about dying in prison were often influenced by the perceived lack of adequate
      health care and the indifference of prison staff and other instances of penal
      harm.

PMID- 20039532
TI  - An internet tool to normalize grief.
AB  - This research evaluated the efficacy of a psycho-educational Internet self-help
      tool to educate and support recently (1-6 months) bereaved individuals. The goal
      of the website was to help users normalize their grief to enhance their adaptive
      adjustment. A randomized controlled trial evaluated the gains in social cognitive
      theory constructs and state anxiety. Compared to the control group (N = 34),
      treatment participants (N = 33) reported significant multivariate gains (eta
      square = .191). Significant program effects were obtained on all three outcome
      measures: attitude (eta-square = .177), self-efficacy (eta-square = .106), and
      state anxiety (eta-square = .083). These findings suggest the potential efficacy
      of an Internet-based grief support tool to enhance adaptive adjustment of the
      bereaved.

PMID- 20039533
TI  - Tailoring traditional interviewing techniques for qualitative research with
      seriously ill patients about the end-of-life: a primer.
AB  - Conducting qualitative interviews with seriously ill individuals about end-of
      life issues is challenging for interviewers seeking to understand the problems,
      processes, and experiences individuals undergo when faced with death and dying.
      Although all qualitative interviewers face issues of building trust and obtaining
      answers to their research questions, these issues are exacerbated for
      interviewers of end-of-life issues due to the challenges of debilitated
      participants, sensitive subject matter, and heightened emotionalism. The purpose
      of this article is to offer field-tested techniques to tailor basic interviewing
      practices for discussions of end-of-life issues with seriously ill individuals.
      Use of tailored techniques facilitates the comfort of both interviewer and
      participant and enhances the probability of obtaining complete and accurate data,
      which in turn can improve the effectiveness of subsequent programs, policies, and
      clinical practice based on research findings.

PMID- 20039535
TI  - [Investigation on a chronic benzene poisoning accident in an air conditioning
      parts factory].

PMID- 20039534
TI  - [Role of extracellular signal-regulated kinase 1/2 on inhibition of N-acetyl
      seryl-aspartyl-lysyl-proline on proliferation and collagen synthesis of cultured
      rat pulmonary fibroblasts induced by platelet-derived growth factor].
AB  - OBJECTIVE: To investigate the role of extracellular signal-regulated kinase 1/2
      on the inhibition of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the
      proliferation and collagen synthesis of cultured rat pulmonary fibroblasts
      induced by platelet-derived growth factor (PDGF). METHODS: Pulmonary fibroblasts
      were prepared from lungs of neonatal Wistar rats as described previously. Cells
      were divided into 4 groups: (1) control group (0.4% FBS group); (2) PDGF (10
      ng/ml) stimulated group; (3) PD98059+PDGF group (25 micromol/L PD98059+10 ng/ml
      PDGF); (4) AcSDKP+PDGF group (10(-8) mol/L AcSDKP+10 ng/ml PDGF). All experiments
      were performed in the fourth passages. Metabolic activity of fibroblasts was
      observed by MTT, and expressions of type I and type III collagen were measured by
      immunocytochemistry and western blot. Expressions of phospho-ERK1/2 and ERK1/2
      were detected by western blot. RESULTS: Compared with control group, exposure of
      pulmonary fibroblasts to 10 ng/ml PDGF increased cell metabolic activity,
      expression of type I and type III collagen and phosphorylation of ERK1/2. 25
      micromol/L PD98059 and AcSDKP both could inhibit the metabolic activity of
      pulmonary fibroblasts, type I and type III collagen synthesis and phosphorylation
      of ERK1/ 2 induced by PDGF, with significant differences (P < 0.05). AcSDKP+PDGF
      group compared with PDGF stimulated group, metabolic activity of pulmonary
      fibroblasts decreased to 77.4%. Immunocytochemistry result showed that in
      AcSDKP+PDGF group, expressions of type I and type III collagen decreased to 69.3%
      and 67.2% compared with those of PDGF stimulated group. Western blot result
      showed that in AcSDKP+PDGF group, expressions of type I and type III collagen
      decreased to 92.4% and 78.0%, phospho-ERK1/2 decreased to 83.5% compared with
      those of PDGF stimulated group, with significant differences (P < 0.05).
      CONCLUSION: ERK1/2 plays an important role in the inhibition of AcSDKP on the
      proliferation and collagen synthesis of cultured rat pulmonary fibroblasts
      induced by PDGF.

PMID- 20039536
TI  - [Antifibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline mediated by
      regulation of transforming growth factor beta and connective tissue growth factor
      expression on rats with silicosis].
AB  - OBJECTIVE: To investigate whether the effect of N-acetyl-seryl-aspartyl-lysyl
      proline (AcSDKP) on transforming growth factor beta (TGF-beta1) and connective
      tissues growth factor (CTGF) was involved in AcSDKP's antifibrotic effect on the
      rats with silicosis. METHODS: Rats were divided into 6 groups randomly, 10 rats
      in each group: Control of silicotic model: 1.0 ml normal sodium and was killed
      after 4 or 8 weeks; Silicotic model 1: 50 mg/ml silica suspension and was killed
      after 4 weeks; Silicotic model 2: 50 mg/ml silica suspension and was killed after
      8 weeks; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally
      instilled with 50 mg/ml silica suspension for 4 weeks, AcSDKP 800 microg/(kg x d)
      was administered into every rat and rats were killed at the 8 weeks; Preventing
      fibrosis treatment of AcSDKP: after AcSDKP [800 microg/(kg x d)] was administered
      into every rat for 48 hours, each rat was intratracheally instilled with 50 mg/ml
      silica suspension and rats were killed at the 8 weeks. Lung fibrosis in
      morphology was observed by HE staining. The expressions of TGF-beta1 and CTGF in
      lung were observed by immunohistochemistry. The mRNA expressions of TGF-beta1 and
      CTGF in lung were observed by real-time PCR. RESULTS: In anti-fibrosis treatment
      of AcSDKP group, protein expression of TGF-beta1 and CTGF were (0.244 +/- 0.016)
      and (0.241 +/- 0.017) respectively, and significantly lower that those in the
      silicotic model 1 and 2 groups; mRNA expressions of TGF-beta1 and CTGF decreased,
      mRNA expressions of CTGF were significantly lower that those in the silicotic
      model 1 and 2 groups (P < 0.05); In preventing fibrosis treatment of AcSDKP
      group, protein expression and mRNA expression of TGF-beta1 were significantly
      lower that those in the silicotic model 2 group (P < 0.05). CONCLUSION: AcSDKP
      can decrease the expressions of TGF-beta1 and CTGF in lung tissues of the rats
      with experimentally induced pulmonary fibrosis.

PMID- 20039537
TI  - [Effect of human silicotic alveolar macrophages on expression of matrix
      metalloproteinase, tissue inhibitor of metalloproteinase and collagen in human
      lung fibroblasts].
AB  - OBJECTIVE: To study the effect of culture supernatant of alveolar macrophage
      alveolar macrophages (AM) stimulated by SiO2 on the expression of matrix
      metalloproteinases (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and
      collagen of fibroblast human embryonic lung fibroblasts (HELF) in the development
      of silicosis fibrosis. METHODS: AMs were collected from a silicotic patient by
      bronchoalveolar lavage and exposed to SiO2, cultured human embryo lung fibroblast
      were allocated into a treated group, a control group, a positive group, and a
      blank group. HELF was incubated with the cultured supernatant of AMs for 6, 12,
      18, 24, 36, 48 h. Immunocytochemical and Western blot technology were used to
      detect MMP-1 and TIMP-1 expressions in HELF and collagen expression in
      supernatant of HELF respectively. RESULTS: The supernatant of AM exposed to SiO2
      significantly decreased the expressions of MMP-1 (0.0605 +/- 0.0201, 0.0519 +/-
      0.0117, 0.0412 +/- 0.0105 and 0.0213 +/- 0.0106 in the treated group at 18, 24,
      36 and 48 h) compared with the control group and the blank group (P < 0.05, P <
      0.01) but stimulated expressions of TIMP-1 and collagen (P < 0.05, P < 0.01). The
      ratio of TIMP-1 to MMP-1 increased. The ratio of TIMP-1 to MMP-1 was positively
      correlated with the expression of collagen III (r = 0.88, P < 0.01). CONCLUSION:
      Through AM mediation SiO2 can accelerate the expression of TIMP-1 and collagen,
      and inhibit the expression of MMP-1. The imbalance between the expression of TIMP
      1 and that of MMP-1 is related with the abnormal increase in collagen III.

PMID- 20039538
TI  - [Two new anthropometric panels of respirator fit test for Chinese adult workers].
AB  - OBJECTIVE: To develop two new respirator fit test panels using data from
      anthropometric survey of Chinese adult workers: bivariate panel and principal
      component analysis (PCA) panel for meeting the requirements of respirator fit
      design and testing and evaluate the applicability of the two different fit test
      panels for current Chinese workers. METHODS: An anthropometric database based
      upon anthropometric data of current Chinese workers was used for panel design.
      The bivariate panel was based upon the bivariate distribution of the face length
      and face width measurements, and the PCA panel was developed using principal
      components analysis of 10 stable facial dimensions (minimum frontal breadth, face
      width, bigonial breadth, face length, interpupillary distance, head breadth, nose
      protrusion, nose breadth, nasal root breadth, subnasale-sellion length). The
      distribution of Chinese workers across the panels was used to analyze the panels'
      applicability for Chinese workers. RESULTS: The bivariate panel and PCA panel
      developed in this study consisted of 10 cells and 8 cells respectively, covered
      96.9% (male 95.4%, female 98.4%) and 96.5% (male 95.1%, female 98.1%) of the
      current Chinese workers, respectively. The distribution of workers across both
      panels was uniform. Each cell contained 4.6% - 21.7% of the population in the
      bivariate panel and 10.4% - 14.6% of the population in the PCA panel. The LANL
      full-face piece respirator fit test panel covered only 70.9% of the Chinese
      workers, It was thought to be no longer adequate for the Chinese adult workers.
      CONCLUSION: New respirator fit test panels based on updated anthropometric
      database and distributions specific to Chinese workers may be more beneficial for
      applications in China.

PMID- 20039539
TI  - [Interaction between malignant transformation of human pulmonary epithelial cells
      and activation of fibroblasts induced by Yunnan tin mine dust].
AB  - OBJECTIVE: To study the interaction between transformation of human pulmonary
      epithelial cells and activation of fibroblasts induced by Yunnan tin mine dust.
      METHODS: (1) The immortalized human bronchial epithelial cell line BEAS-2B and
      human embryo lung fibroblast cell line WI-38 were grown in MEM medium containing
      5% and 10% FBS, respectively, at 37 degrees C and 5% CO2 with saturated humidity.
      The cells were subcultured every 6 days. BEAS-2B cells and WI-38 cells were
      induced with Yunnan tin mine dust on every other generation at the concentration
      of 100 microg/ml. From the 11th generation, the cells were co-cultured.
      Epithelial cell transformation was tested using concanavalin A (ConA)
      agglutination and anchorage-independent growth assays. The cell cycles were
      analyzed through flow cytometry. The expressions of alpha-SMA in fibroblasts were
      determined with immunocytochemistry. RESULTS: (1) Cell morphology of mine dust
      exposed epithelial cells began to transform at the 28th generation. Similar
      transformations were observed with mine dust-induced epithelial cells co-cultured
      with fibroblasts from the 20th generation and mine dust-induce epithelial cells
      co-cultured with mine dust-induced fibroblasts from the 16th generation. ConA
      agglutination assay and anchorage-independent growth assays were negative in
      normal BEAS-2B cells. At the 26 th generation, the agglutination test result of
      the mine dust-exposed epithelial cells was positive. Co-cultured with fibroblasts
      and mine dust-exposed fibroblasts, the agglutination time of the mine dust
      exposed epithelial cells became short. Epithelial cell anchorage-independent
      growth assay was positive for mine dust-exposed epithelial cells co-cultured with
      fibroblasts at the 36th generations and for mine dust-exposed epithelial cells co
      cultured with mine dust-exposed fibroblasts at the 26th generations. The clone
      formation rate of the 26th generation was 6.00 per thousand +/- 1.00 per thousand
      and 15.33 per thousand +/- 2.52 per thousand respectively, with the significant
      differences (P < 0.05). With generation adding, the portion of S phase increased
      for mine dust-exposed epithelial cells. (2) At the 26th generations, fibroblasts
      expressed alpha-SMA. Co-cultured with epithelial cell, the alpha-SMA expression
      of fibroblasts increased. Especially, positive cell numbers and intensity of
      staining dramatically increased with generation adding. CONCLUSIONS: (1) The tin
      mine dust can induce malignant transformation of human pulmonary epithelial cells
      BEAS-2B and activation of fibroblasts WI-38. (2) The epithelial cells are major
      target in carcinogenesis induced by Yunnan tin mine dust. (3) Transformation of
      epithelia and activation of fibroblasts co-evolve in the developing process of
      induced lung cancer by Yunnan tin mine dust.

PMID- 20039540
TI  - [Expression of p14(ARF) and E2F-1 in lung cancer in Gejiu and Xuanwei regions of
      Yunnan Province].
AB  - OBJECTIVE: To investigate the correlations between p14(ARF) and E2F-1, and the
      role of their alterations in the tumorigenesis of the lung cancer in Gejiu and
      Xuanwei regions in Yunnan Province for providing the important experiment basis
      in revealing the molecular mechanism and looking for new markers for early
      diagnosis of lung cancer. METHODS: The expression of p14(ARF) and E2F-1 was
      detected at theirs protein level by Immunohistochemistry S-P method in 30
      specimens of lung cancer of Gejiu tin miners, 30 specimens of lung cancer of
      Xuanwei peasants and 20 specimens of normal lung tissue. E2F-1 mRNA was detected
      by ISH in 25 specimens of lung cancer of Gejiu tin miners, 25 specimens of lung
      cancer of Xuanwei peasants and 10 specimens of normal lung tissue. The positive
      signals were quantitatively analysed by HPIAS-100. RESULTS: The positive unit
      (PU) of p14(ARF) and E2F-1 was 16.44 +/- 4.85 and 47.39 +/- 5.43 in Gejiu group,
      and 16.79 +/- 3.55 and 48.15 +/- 9.11 in Xuanwei group. Expression of p14(ARF)
      and E2F-1 protein in lung cancer of Gejiu and Xuanwei were statistically
      different compared with that in the normal lung (P < 0.01) respectively; The PU
      of E2F-1 mRNA was 48.58 +/- 7.75 in Gejiu group, and 49.41 +/- 8.53 in Xuanwei
      group, which was higher than that in normal tissue group. The differences were
      significant (P < 0.01). There was positive correlation between the expression of
      E2F-1 protein and E2F-1 mRNA in Gejiu group, Xuanwei group and normal group (P <
      0.01, r = 0.833). The expression of p14(ARF) protein was significantly negatively
      correlated with the expression of E2F-1 protein (P < 0.01, r = -0.830).
      CONCLUSION: There is the over-expression of E2F-1 gene and the deletion of
      p14(ARF) gene in the tumorigenesis of the lung cancer in Gejiu and Xuanwei
      regions in Yunnan Province. Over-expression of E2F-1 protein in lung cancer may
      be caused by enhanced transcription.

PMID- 20039541
TI  - [Histopathology and ultrastructure changes of retina in rats exposed to n
      hexane].
AB  - OBJECTIVE: To investigate the injury in the retina of rats exposed to n-hexane.
      METHODS: Thirty-two SD male rats were randomly divided into control group and
      four n-hexane groups. The rats in the four n-hexane groups inhaled 35.2 g/m3 n
      hexane statically for 1, 3, 7 and 14 days respectively (6 rats in every group)
      while 8 rats in the control group inhaled air. Histopathology and ultrastructure
      changes of the retina of rats were analyzed. RESULTS: Rats in control group had
      clear layers of retinal structure, stained evenly and with regular cell shape.
      Retinal degeneration was observed in the rats exposed to n-hexane for 7 d and 14
      d, and aggravated by degrees with time exposed to n-hexane. In the rats exposed
      to n-hexane for 14 d, the outer segments of photoreceptor were arranged in a
      confusing order, and topically there appeared dissolution; in the inner segments,
      mitochondria were swollen or disappeared. Pyknotic chromatin and cytoplasmic
      edema were observed in the outer nuclear layer. There were degeneration of
      horizontal cells, bipolar cells and amacrine cells in the inner nuclear layer.
      Cytoplasmic edema and organelle dissolution were observed in ganglionic cells. In
      the neurofibromas layer, outer and inner plexiform layers, there was neuron cell
      tuber edema, and the microfilament and vacuole of synapse decreased. CONCLUSION:
      The histopathology and ultrastructure of retina are damaged in the rats exposed
      to n-hexane, thus leading to ocular fundus disease.

PMID- 20039542
TI  - [Genetic damage of mammalian cells induced by nickel-refining fumes].
AB  - OBJECTIVE: To study the effects of two kinds of nickel-refining fumes on DNA
      damage of NIH/3T3 cell and the difference. METHODS: NIH/3T3 cells were treated by
      two kinds of nickel fumes collected from smelting furnace and refining workshop
      of a nickel-smeltery, and PBS taken the place of nickel-smelting fumes was used
      as negative control. Several hours later, the cytotoxicity of on NIH/3T3 cells
      was detected with MTT colorimetric assay, and the DNA damage was also measured by
      comet assay (single cell gel electrophoresis). RESULT: With the extension of
      exposure time and increasing of concentration, the living rate of NIH/3T3 cells
      was decreased; the tail rate, tail extent moment and tail DNA percent of NIH/3T3
      cell induced by these two refining fumes were increased. After cells were treated
      with 100.00 microg/ml of nickel-smelting fume for 48 h, the living rate of
      NIH/3T3 cells was 24.5% and 26.5% respectively. The tail length of NIH/3T3 cell
      induced by these two refining fumes was not significant difference. Tail DNA
      percent of NIH/3T3 cell induced by smelting furnace fume was higher than negative
      control group (P < 0.05). The tail rate, and tail DNA percent (except 12.5
      microg/ml and 50.0 microg/ml treated 2 h group) of NIH/3T3 cell induced by
      refining workshop fume was higher than negative control group (P < 0.05).
      CONCLUSION: Nickel-smelting fume could depress the survival rate of NIH/3T3
      cells, and induce different degree DNA damage of NIH/3T3 cell.

PMID- 20039544
TI  - [Analysis of pneumoconiosis cases in a city between 1960 and 2007].

PMID- 20039543
TI  - [Investigation on citric acid dusts induced mass tooth erosion onset].

PMID- 20039545
TI  - [Verification and analysis of monitoring quality of injuries in hospitals with
      grey correlation analysis method].

PMID- 20039546
TI  - [Investigation on status quo of organic solvent exposure in work places of
      factories in Guangzhou].

PMID- 20039547
TI  - [Effect of trichloroethylene on expressions of Rho GDI alpha, ANXA3 and GLO1 in L
      02 liver cells].

PMID- 20039548
TI  - [Clinical analysis of acute Avermectins poisoning].

PMID- 20039549
TI  - [Clinical analysis of acute dichloropropane and trichloropropane poisoning].

PMID- 20039550
TI  - [Analysis of clinical characteristics of subacute 1,2-dichloroethane poisoning].

PMID- 20039551
TI  - [Clinical analysis of Amanita verna poisoning induced liver injury].

PMID- 20039552
TI  - [Application of clinical pathway in treatment of pneumoconiosis with whole lung
      lavage].

PMID- 20039553
TI  - [Changes of plasma prethrombotic state molecular markers levels in silicosis
      patients].

PMID- 20039554
TI  - [Survey on occupational knowledge, attitude, behavior and requirements for health
      education of rural migrant workers].

PMID- 20039555
TI  - What the community needs and deserves.

PMID- 20039556
TI  - A different view.

PMID- 20039557
TI  - Anchoring action with our values.

PMID- 20039558
TI  - Professional nursing judgement--keeping the system safe.

PMID- 20039559
TI  - Let them eat Fish.

PMID- 20039560
TI  - No easy fix for alcohol problem.

PMID- 20039561
TI  - You and your new nurses' award.

PMID- 20039563
TI  - Continuing competency requirements for RN midwives.

PMID- 20039562
TI  - What you need to know about national registration and accreditation.

PMID- 20039564
TI  - The quiet achiever.

PMID- 20039565
TI  - Oncology nurses are leaders in the transformation of geriatric oncology care.

PMID- 20039566
TI  - Do you know how to care for older adults?

PMID- 20039568
TI  - Prevent bloodstream infections from access devices.

PMID- 20039569
TI  - Implantable device monitors treatment effectiveness.

PMID- 20039567
TI  - Learn to assess for and manage trastuzumab-induced cardiotoxicity.

PMID- 20039570
TI  - ONS works to address gaps in geriatric oncology care.

PMID- 20039571
TI  - 'Tis the season.

PMID- 20039572
TI  - Who cares?

PMID- 20039573
TI  - To a dear and probably glorious physician ... concerning a transfer dilemma.

PMID- 20039575
TI  - Where can I get CME? Top physician resources in TN.

PMID- 20039574
TI  - HIPAA privacy rules an unfunded mandate?

PMID- 20039576
TI  - Where have all the primary care docs gone?

PMID- 20039577
TI  - Communication is often the weakest link.

PMID- 20039579
TI  - The University of Tennessee Teaching Effectiveness Score.
AB  - OBJECTIVES: We studied medical student evaluation of their Obstetrics and
      Gynecology faculty defined as Teaching Effectiveness Score (TES). We also
      evaluated the role of sharing TES to all faculty transparently in enhancing
      teaching interest among faculty. METHODS: Students evaluated faculty with
      questions: Which faculty enhanced or least aided your learning and why? The TES
      was calculated by adding the number of positive comments, subtracting the
      negative comments, and dividing this total by the amount of students on the
      rotation. TES was distributed to all attending physicians via email allowing
      faculty to see each other's evaluaton. RESULTS: 203 third-year medical students
      evaluated 25 attending physicians. The median TES was 3.2 percent (range -0.4 to
      100 percent) with two attending physicians scoring high (p<0.01). A trend test
      showed the change was quadratic: the faculty's TES increased initially then
      decreased over time (p=0.053 to 0.409). A high TES is associated with teaching
      awards. High TES is not associated with age (p=0.77), academic rank (p=0.71),
      gender (p=0.89), race (p=0.55). CONCLUSION: TES measured teaching effectiveness
      as perceived by students. Transparency of TES induced interests in teaching
      initially but then declined with time.

PMID- 20039580
TI  - Tennessee's first medical journal.

PMID- 20039578
TI  - RAC has arrived in TN; here's what's ahead.

PMID- 20039581
TI  - The legal path to "death with dignity" acts in the United States.

PMID- 20039582
TI  - White paper: "walking speed: the sixth vital sign".

PMID- 20039583
TI  - Effects of an exercise program to increase hip abductor muscle strength and
      improve lateral stability following stroke: a single subject design.
AB  - BACKGROUND AND PURPOSE: Persons with lower extremity weakness following stroke
      often demonstrate difficulty with weight transfer and paretic lower extremity
      loading. These deficits, in turn, can lead to problems with lateral stability, or
      the ability to control movement of the center of mass in the frontal plane. The
      primary aim of this study was to examine the efficacy of an individualized home
      exercise program in improving hip abductor muscle strength and lateral stability
      in a subject with chronic stroke. METHODS: An A-B-A treatment-withdrawal single
      subject design was used. The subject was a 70-year-old male who had experienced a
      left hemispheric stroke 36 months prior to initiation of the study. Bilateral hip
      abductor muscle strength, single limb stance (SLS), timed 360 degrees turn, Step
      Test, and 10-m walk at self-selected and fast speeds were recorded at regular
      intervals during the baseline (A-I), treatment (B), and treatment-withdrawal (A
      2) phases. The home exercise program in the B phase consisted of lower extremity
      weight bearing and weight transfer activities and exercise on a lateral training
      device 3 to 5 times a week for 6 weeks. The Berg Balance Scale (BBS) and Stroke
      Impact Scale (SIS) were administered at the completion of each phase and at 6
      week follow-up. Data were analyzed using visual analysis and the split-middle
      method of trend estimation. RESULTS: Mean levels of all measures improved from A
      1 to B phases, with significant increases in trend for hip abductor muscle
      strength and SLS bilaterally. Most improvements were maintained during the
      treatment-withdrawal (A-2) phase and at follow-up. CONCLUSION: A home exercise
      program that includes exercise on a lateral training device shows promise for
      producing increases in hip abductor muscle strength and accompanying improvements
      in some measures of physical performance and disability in persons with chronic
      stroke.

PMID- 20039584
TI  - A rehabilitative ultrasound imaging investigation of lateral abdominal muscle
      thickness in healthy aging adults.
AB  - PURPOSE: Rehabilitative ultrasound imaging (RUSI) is used to evaluate lateral
      abdominal muscle size and function during the abdominal drawing-in maneuver
      (ADIM), an exercise used to improve lumbar spine stability. Little is known about
      the size and performance of these muscles in healthy aging adults. The purpose of
      this study was to investigate, using RUSI, the size and symmetry of the lateral
      abdominal muscles bilaterally at rest and during the ADIM in healthy older adults
      and the reliability of these measurements. METHODS: Three ultrasound images of
      the right and left lateral abdominal muscles were taken at rest and during the
      ADIM in 12 healthy older adults. Thickness of the transversus abdominis muscles
      (TrA), internal oblique (IO), and external oblique (EO) were measured for all
      images. Intraclass correlation coefficients were computed using model 3, form 1
      (ICC3,1). Two ratios of the abdominal muscles were calculated in the relaxed and
      contracted states. Paired t-tests were used to compare relaxed muscle thickness
      to contracted muscle thickness for all 3 muscles for each side. To test further
      for interactions of side and contractile state, 2 x 2 repeated measures ANOVAs
      were performed. Side-to-side differences in absolute and relative thickness were
      assessed with paired t-tests for the TrA and IO muscles. Absolute and relative
      side-to-side muscle symmetry indices were computed for each muscle at rest.
      RESULTS: There was a significant difference in muscle thickness between the
      contracted and relaxed states for both the TrA and IO. There was no significant
      difference between left/right muscle thickness for the TrA or IO at rest or
      during the ADIM. The TrA nearly doubled in size while thickness of the IO + EO
      stayed relatively constant during the ADIM. Reliability for absolute muscle
      thickness was generally excellent: ICCs3,1 ranged from 0.95 to 1.00 for intra
      image reliability; 0.77 to 0.97 for inter-image reliability. CONCLUSIONS: These
      findings support symmetrical and preferential activation of the TrA during the
      ADIM in healthy older adults. Continued research on the use of RUSI as a tool for
      both assessment and intervention in older adults is needed.

PMID- 20039585
TI  - Descriptive analysis of fatal falls of older adults in a Midwestern county in the
      year 2005.
AB  - BACKGROUND AND PURPOSE: Falls in older adults continues to be a serious problem
      worldwide. Falls are the leading cause of injury related deaths among older
      adults in the United States. Though, there have been many effective fall
      prevention programs reported, there is still a gap in the literature that
      addresses the effectiveness of interventions that prevent fall related deaths.
      The purposes of this study are to (1) carry out preliminary descriptive analyses
      on persons who died after a fall in the year 2005 in one Midwest county and (2)
      compare county data to national and international statistics. METHODS AND
      MATERIALS: With cooperation of the County Medical Examiner, 103 death
      certificates and medical records of older adults who died due to complications
      after a fall from the year 2005 were retrospectively reviewed. Descriptive
      statistics were developed for: (1) demographics prior to the fall, (2) fall
      descriptors including activity, place of fall, and outcome of the fall, (3)
      outcomes after fall including: injuries incurred, cause of death, and days from
      fall to death. RESULTS: Average age of people who died after a fall was 85.4
      years. More than 50% of the fatal falls occurred in the home and resulted in a
      hip fracture. The most common cause of death was complications of a hip fracture
      with an average of 31 days from fall to death. CONCLUSION: Despite the
      recommendations regarding fall prevention, there still is a need to investigate
      the significant number of fatalities after falls.

PMID- 20039586
TI  - Outcomes for aging adults following total hip arthroplasty in an acute
      rehabilitation facility versus a subacute rehabilitation facility: a pilot study.
AB  - PURPOSE: The purpose of our study was to determine if aging adults who received
      rehabilitation following total hip arthroplasty (THA) due to osteoarthritis had
      better short-term outcomes in an Inpatient Rehabilitation Facility (IRF) compared
      with those currently receiving rehabilitation in subacute rehabilitation units.
      METHODS: Thirty-six adults, aged 65 to 88 years, who received inpatient
      rehabilitation following THA secondary to osteoarthritis participated in this
      study. A prospective descriptive study of 4 aging adults receiving rehabilitation
      in 2 subacute rehabilitation facilities and a retrospective descriptive study of
      32 aging adults who received rehabilitation in an IRF were conducted.
      Socioeconomic, medical, rehabilitative care, and demographic data were obtained
      by review of participants' medical charts. FIM scores of the aging adults in the
      IRF were obtained by chart review, while FIM scores of the aging adults in the
      subacute facilities were collected by one of the investigators. RESULTS: In this
      sample, the aging adults in the IRF appeared to have greater changes in total FIM
      score, motor subscale FIM score, and self-care subscale FIM score than the aging
      adults in the subacute facilities. In this sample, discharge setting appeared
      similar for the aging adults in the two rehabilitation settings. CONCLUSIONS: It
      is imperative that further research determine if rehabilitation provided in
      different settings that offer different intensities and durations of
      rehabilitation affects functional outcomes for aging adults following THA
      procedures.

PMID- 20039587
TI  - The long-term contribution of muscle activation and muscle size to quadriceps
      weakness following total knee arthroplasty.
AB  - PURPOSE: Many older individuals have persistent quadriceps strength impairments
      after a total knee arthroplasty (TKA). A combination of muscle atrophy and
      neuromuscular activation deficits apparently contributes to residual strength
      impairments. The purpose of this short report is to describe the contribution of
      quadriceps muscle activation and muscle volume to impaired muscle strength in
      older individuals an average of 21 months following a TKA. METHODS: Seventeen
      individuals (males: 3, females: 14; mean age: 68 yrs +/- 8.7; BMI: 33 +/- 4.8
      kg/m2; number of TKA: 24; average postoperative months: 21 +/- 11.3) recruited
      from an orthopaedic surgeon's practice provided their written consent and
      participated in this study. Quadriceps strength (MVIC) and voluntary quadriceps
      muscle activation (QA) were measured with use of a burst-superimposition
      technique in which a supramaximal burst of electrical stimulation is superimposed
      on an MVIC. Quadriceps volume (QV) was assessed from magnetic resonance images of
      the quadriceps. RESULTS: The mean quadriceps strength was 107.3 Nm +/- 36.4
      (range: 43.22 - 205.2). The mean QA (as described with a central activation
      ratio) was 0.97 +/- 0.04 (range: 0.83 - 1.00). The mean QV was 1093 cm3 +/-
      311.80 (range: 653.66 - 1706.56). QA and QV explain 85% of the variance in
      quadriceps strength (R2 = .85, p < 0.001), with QV having the greatest
      contribution to strength (R2 = .77, p < 0.001). CONCLUSIONS: QV is a much
      stronger predictor of quadriceps strength than QA in individuals more than 1 year
      following TKA. Activation levels contributed little to strength one year
      following TKA, compared to its profound contribution in the first few
      postoperative months. Physical therapy interventions focused on improving muscle
      size in this population should be considered more relevant than countermeasures
      addressing neuromuscular activation.

PMID- 20039589
TI  - Vital statistics system.

PMID- 20039588
TI  - Sarcopenia--mechanisms and treatments.
AB  - BACKGROUND: Sarcopenia is a consequence of aging. This atrophic event is
      responsible for decrease in strength and associated functional deficits seen in
      the aging adult. PURPOSE: This paper reviews: (1) the mechanisms contributing to
      sarcopenia, (2) the impact of age-related changes in muscle composition on 3
      processes integral to muscle function, (3) the efficacy of pharmaceuticals and
      over-the-counter nutritional supplements in the management of sarcopenia, (4)
      experimental use of pharmaceutical regulation of myostatin to increase muscle
      mass and strength in animal models, and (5) efficacy of resistance training as a
      means of maintaining or recovering muscle mass and strength. METHODS: PubMed was
      searched for relevant research articles using the following descriptors:
      sarcopenia, aging, muscle mass, muscle performance, muscle strength, myostatin,
      testosterone, growth hormone, dehydroepiandrosterone, hormone replacement,
      nutrition, resistance training, and endurance training. RESULTS: Sarcopenia is
      mediated by multiple mechanisms, including alpha-motor neuron death, altered
      hormone concentrations, increased inflammation, and altered nutritional status.
      Age-related changes within muscle likely affect processes integral to muscle
      function. These changes negatively influence muscle performance directly or by
      contributing to sarcopenia. Pharmaceutical or supplement interventions to treat
      sarcopenia have not proved encouraging to date, either lacking or providing
      limited efficacy, along with the potential for negative health consequences. In
      contrast, resistance training has proven safe and highly effective for increasing
      muscle mass and strength in aging adults. CONCLUSION: Sarcopenia is a
      multifactorial consequence of aging that will affect many adults. Resistance
      training is the most effective and safe intervention to attenuate or recover some
      of the loss of muscle mass and strength that accompanies aging.

PMID- 20039590
TI  - Survival of newborns: implications for achieving the millennium development goal
      in Bangladesh.
AB  - The global burden of neonatal deaths is around 37% of all under-five deaths
      (UNICEF 2008). In Bangladesh, neonatal deaths account for almost half of all
      under-five mortality. Most newborn deaths in Bangladesh take place at home and in
      the absence of a skilled hand. The target of Millennium Development Goal 4 for
      Bangladesh is to reduce under-five mortality by two thirds by 2015 from 1990
      levels. The objectives of this article are to give an overview of newborn health
      in Bangladesh and provide a strategy for further reducing under-five mortality to
      achieve MDG 4. Data for this study were obtained from the Bangladesh Demographic
      and Health Survey (BDHS) 2004 data set (National Institute of Population and
      Training [NIPORT] et al. 2005). According to the BDHS, under-five mortality in
      Bangladesh declined from 133 per 1000 live births in 1991 to 88 per 1000 in 2001,
      about 4.1% per year. However, the decline was faster between 1991 and 1997 than
      from 1997 to 2001. The BDHS shows that while neonatal deaths were 39% of all
      under-five deaths in 1991, they constituted almost half in 2001. The highest
      concentration of newborn deaths occurred during delivery and within the first 24
      hours of birth. Reducing newborn deaths will be an important strategy to achieve
      MDG 4.

PMID- 20039591
TI  - Development of an effective public health screening program to assess hearing
      disabilities among newborns in Shanghai: a prospective cohort study.
AB  - BACKGROUND: An effective, systematic program of screening, diagnosis and
      intervention against hearing loss in infants could help them avoid developmental
      impediments and could help society stem preventable healthcare burdens. We
      assessed the feasibility and outcomes of a new public health universal newborn
      hearing screening program (UNHSP) for neonates born in Shanghai. METHODS: From
      March 2002 to June 2007, we conducted a two-stage hearing loss screening program
      for neonates born at all 105 delivery hospitals in Shanghai. Institutional
      participants in the program followed standardized testing criteria and
      procedures. The first stage of screening occurred in the hospital during the
      third day post-birth; positive infants underwent a second-stage outpatient
      screening on Day 42. Positive infants were examined at clinical diagnosis
      centres, and interventions were conducted at rehabilitation centres. In 2003, a
      random sample of parents were interviewed about the program, and their level of
      stress over learning their child screened positive were recorded and analyzed.
      FINDINGS: Overall, our program screened 72.98% of eligible infants and provided
      effective interventions within six months to 86.31% of those with hearing oss.
      During the 5-year study, first-stage screenings assessed 90.85% of 616,880
      eligible infants and found 12.16% positive. Day 42 screenings had a 65.68%
      participation rate and a positive rate of 14.75%. Of these, 0.146% were deemed
      permanently hearing impaired within three months of birth. Parental satisfaction
      measures exceeded 90%. INTERPRETATION: A government-sponsored public health
      program to screen, diagnose, treat and provide interventions for all newborns
      with permanently hearing impairment can be effectively implemented and can
      achieve outcomes that surpass comparable clinical initiatives.

PMID- 20039592
TI  - Mental health symptoms among rural-to-urban migrants in China: a comparison with
      their urban and rural counterparts.
AB  - OBJECTIVE: To examine the mental health symptoms among rural-to-urban migrants in
      China, in comparison with representative samples of their counterparts in the
      rural areas from where they emigrated and urban communities to which they
      immigrated. METHODS: A cross-sectional survey conducted in 2004-2005 in China.
      Both rural-to-urban migrants (n=1006) and urban residents (n=1000) were recruited
      in Beijing; the rural resident sample (n=1020) was recruited from the eight
      provinces of origin for 75% of the migrant sample. Mental health symptoms were
      measured using the Symptom Checklist-90 (SCL-90). RESULTS: Both rural-to-urban
      migrants and rural residents scored higher than urban residents in all the SCL-90
      global indices and subscales. The rural-to-urban migrants scored higher than
      rural residents on the SCL-90 Positive Symptom Distress Index and two subscales
      (depression and psychoticism). The difference remained significant after
      controlling for a number of key individual characteristics (age, gender, marital
      status, education, income and perceived general health) in the multivariate
      model. CONCLUSIONS: The data in the current study demonstrate that rural-to-urban
      migrants suffer from lower mental health status than both urban residents in the
      immigrating communities and their rural counterparts in the emigrating
      communities. The data suggest a possible deteriorative effect of migratory
      experience on mental health status among rural-to-urban migrants in China and
      suggest an urgent need for etiological studies and for mental health promotion
      and prevention efforts among this growing population.

PMID- 20039593
TI  - Household use of inpatient healthcare services in India.
AB  - Improving household use of healthcare facilities is a vital public health
      strategy to reduce burden of disease in India. Our study set out to understand
      the importance of the interplay of household characteristics and state-level
      public health covariates in accessing inpatient healthcare services. The study is
      based on morbidity and healthcare data from the 60th round of the Indian National
      Sample Survey Organisation, 2004. We used multilevel logistic regression to
      disentangle dependence among the observations. We observed that the education
      level of household heads and the household's economic well-being had a
      significant positive influence on accessing inpatient healthcare services.
      Distance from the household to the health facility showed a significant inverse
      association with use of health facilities for inpatient treatment. Further, we
      found a significant variation across the states. Variability in accessing
      inpatient services at the household and state levels are 1.7% and 21%
      respectively.

PMID- 20039594
TI  - Multiple forces working in unison: the case of rapid improvement of vital
      statistics in South Africa post-1996.
AB  - In a period of about five years, from 1997 to 2002, South Africa remarkably
      improved the coverage and production of its vital statistics. This period
      witnessed the entrance of South Africa into the select league of countries that
      publish statistics on multiple causes of death and that make use automatic coding
      of causes of death. These achievements were accomplished through multiple forces
      working in unison. Some of the important factors contributing to the achievement
      were lessons learned from study tours to Australia, Sweden and the U.S.A. The
      paper describes these lessons and how they were adapted to suit the South African
      reality. Comparison is made between the status of demographic statistics by the
      end of apartheid and in the post-apartheid era. Stakeholder relationships that
      shaped the transformation of demographic statistics in the new South Africa are
      also discussed.

PMID- 20039595
TI  - Management of hirsutism.
AB  - Hirsutism is a relatively common condition affecting about 5%-O10% of women of
      childbearing age. Herein, we present an overview of hirsutism with emphasis on
      its etiology and therapeutic options.

PMID- 20039596
TI  - Body piercing: more than skin deep.
AB  - Young adult populations (18-25 years of age) throughout the world have latched
      onto the mainstream trend of body piercing. Best health care practices for these
      individuals involves the knowledge of proper procedural techniques, postsite
      care, common complications, and treatment modalities.

PMID- 20039597
TI  - Functionalized poly(ethylene glycol)-stabilized water-soluble palladium
      nanoparticles: property/activity relationship for the aerobic alcohol oxidation
      in water.
AB  - The preparation, characterization, and catalytic properties of water-soluble
      palladium nanoparticles stabilized by the functionalized-poly(ethylene glycol) as
      a protective ligand were demonstrated for aerobic oxidation of alcohols in
      aqueous phase. UV/vis spectra and X-ray photoelectron spectroscopy (XPS) proved
      that there was an electronic interaction between the bidentate nitrogen ligand
      and palladium atoms. Transmission electron microscopy and XPS analysis showed
      that the particle size and surface properties of the generated palladium
      nanoparticles can be controlled by varying the amount of protective ligand and
      the kinds of reducing agents. It was found that both the size and surface
      properties of palladium nanoparticles played very important roles in affecting
      catalytic performance. The stabilized metallic palladium nanoparticles were
      proven to be the active centers for benzyl alcohol oxidation in the present
      system, and the water-soluble Pd nanocatalysts can also be extended to the
      selective oxidation of various alcohols.

PMID- 20039598
TI  - A general approach combining diazonium salts and click chemistries for gold
      surface functionalization by nanoparticle assemblies.
AB  - This paper describes a general stepwise strategy combining diazonium salt and
      click chemistries for an efficient gold surface functionalization by gold
      nanoparticles. The procedure first involves the strong covalent bonding to gold
      electrodes of OH-terminated aryl layers derived from the electroreduction of the
      parent diazonium salts. The following step consists in transforming the OH end
      groups to azides in order to obtain "clickable"-active gold surfaces, which could
      further be used as versatile platforms for the subsequent grafting of acetylene
      bearing molecules. The practical interest of the gold surfaces functionalized by
      this stepwise strategy was evidenced through the self-assembly of surface
      enhanced Raman scattering (SERS)-active gold nanoparticles. SERS activity was
      shown to be amplified by the presence of a very strong local electric field
      confinement between the particles and the gold surface.

PMID- 20039599
TI  - Calcium phosphate coated electrospun fiber matrices as scaffolds for bone tissue
      engineering.
AB  - Electrospun polymeric scaffolds are used for various tissue engineering
      applications. In this study, we applied a biomimetic coating method to provide
      electrospun scaffolds from a block copolymer-poly(ethylene oxide terephthalate)
      poly(buthylene terephthalate), with a calcium phosphate layer to improve their
      bioactivity in bone tissue engineering. The in vitro studies with human
      mesenchymal stem cells demonstrated cell proliferation on both uncoated and
      coated samples. No significant effect of calcium phosphate coating was observed
      on the expression of alkaline phosphatase in vitro. Implantation of scaffold-goat
      mesenchymal stem cells constructs subcutaneously in nude mice resulted in bone
      formation in the calcium phosphate coated samples, in contrast to the uncoated
      ones, where no new bone formation was observed. The results of this study showed
      that the biomimetic method can successfully be used to coat electrospun scaffolds
      with a calcium phosphate layer, which improved the in vivo bioactivity of the
      polymer.

PMID- 20039600
TI  - Dynamics of gravity driven three-dimensional thin films on hydrophilic
      hydrophobic patterned substrates.
AB  - We investigate numerically the dynamics of unstable gravity driven three
      dimensional thin liquid films on hydrophilic-hydrophobic patterned substrates. We
      explore longitudinally striped and checkerboard arrangements. Simulations show
      that for longitudinal stripes, the thin film can be guided preferentially on the
      hydrophilic stripes, while fingers develop on adjacent hydrophobic stripes if the
      width of the stripes is large enough. On checkerboard patterns, the film develops
      as a finger on hydrophobic domains, while it spreads laterally to cover the
      hydrophilic domains, providing a mechanism to tune the growth rate of the film.
      By means of kinematical arguments, we quantitatively predict the growth rate of
      the contact line on checkerboard arrangements, providing a first step toward
      potential techniques that control thin film growth in experimental setups.

PMID- 20039601
TI  - Modeling the mechanical response of tetragonal lysozyme crystals.
AB  - We investigate the temperature- and humidity-dependent mechanical response of
      tetragonal lysozyme crystals using a continuum-based crystal plasticity model
      calibrated with existing experimental data. The effects of temperature and
      intracrystalline water are incorporated in the elastic constant of the protein
      crystal as well as the critical resolved shear stress on the slip planes in the
      crystal plasticity model. The critical resolved shear stresses have been deduced
      from Vickers microhardness test data corresponding to different temperatures and
      states of hydration. Compression analyses have then been carried out along
      different crystallographic directions of lysozyme crystals which reveal that
      their mechanical response is highly anisotropic and orientation dependent, being
      purely elastic along the [110] direction but elastoplastic along the [100] and
      [212] directions. An interesting observation is that an increase in temperature
      and the amount of intracrystalline water molecules leads to a decrease in the
      critical resolved shear stress of the slip systems resulting in softening of the
      crystal. The analysis presented in this paper may be applied to the study of
      other protein crystal systems as well as their optimal design for
      biotechnological applications.

PMID- 20039602
TI  - Effect of surface modification on the dielectric properties of BaTiO3
      nanocrystals.
AB  - We present the first direct comparison of the dielectric properties of
      organically modified BaTiO(3) nanocrystals with unmodified BaTiO(3) nanocrystals.
      Well-defined 6 nm BaTiO(3) nanocrystals were functionalized with n
      hexylphosphonic acid (HPA) to give a surface coverage of 2.4 phosphonate
      groups/nm(2). Chemisorption of HPA to the oxide surface occurs mainly via
      tridentate bonding of the deprotonated phosphonate, as determined by (31)P MAS
      NMR, FT-IR, and XPS spectroscopies. The HPA-modified BaTiO(3) (HPA-BaTiO(3))
      nanocrystals possess improved dielectric properties, as demonstrated by decreased
      sensitivity to temperature and frequency for both the dielectric constant and
      dielectric loss. HPA-BaTiO(3) had a much lower dielectric loss than unmodified
      BaTiO(3), which also indicates an improvement in the dielectric quality of the
      material. Such improvements are of potential importance for the fabrication of
      high energy density nanocomposites.

PMID- 20039603
TI  - Enzyme containing redox polymer networks for biosensors or biofuel cells: a
      photochemical approach.
AB  - A photochemical approach to the generation of (microstructured) redox hydrogels
      with incorporated enzymes is presented and evaluated with respect to its
      potential in biosensor and biofuel cell applications. For this,
      poly(dimethylacrylamide) polymers containing both electroactive ferrocene
      moieties and photoreactive benzophenone groups are synthesized and deposited as
      thin films on electrode surfaces. Upon short irradiation with UV light, the
      polymer layer cross links and becomes firmly adhered to the glassy carbon
      electrodes. If glucose oxidase is mixed into the polymer solution prior to
      coating, then glucose-oxidizing electrodes with very high catalytic current
      responses are obtained. The influence of multivalent ions and proteins on the
      performance of the electrocatalytic films is studied. It is found that the
      interaction between bivalent HPO(4)(2-) and the oxidized redox moieties can
      shorten the lifetime of the redox electrodes significantly whereas the same
      electrodes are quite stable in the presence of monovalent ions and the reduced
      form of the mediator. Coating a thin, covalently attached
      poly(dimethylacrylamide) protective layer onto the redox polymer networks can
      greatly reduce the adsorption of proteins onto the surfaces and improve the long
      term stability of the electrodes in physiological environments. Because the
      adsorption of proteins onto unprotected surfaces is one of the major causes of
      bioelectrode failure, this aspect is expected to contribute to the design of more
      biostable sensors and fuel cells.

PMID- 20039604
TI  - Separation and purification of nanoparticles in a single step.
AB  - Reversed-micelle synthesis has been used to generate CTAB-stabilized gold (Au
      NPs) and silver nanoparticles (Ag-NPs). By inducing a phase transition and
      subsequent separation of the background supporting microemulsion, it has been
      possible to extract and purify the NPs from the reaction medium. After addition
      of excess water, the NPs concentrate into an upper octane-rich phase, with
      impurities and reaction debris (in particular CTAB) partitioning into the water
      rich lower phase. UV and (1)H NMR showed that 82% of the original mass of Au-NPs
      can be purified from the excess CTAB and other salt impurities. The concentrated
      and purified NPs can be dried down, by solvent removal, and then redispersed in
      octane. Using the complementary techniques small-angle neutron and X-ray
      scattering (SANS and SAXS), the structures of microemulsions both with and
      without nanoparticles prior to separation, and in both upper and lower phases
      after separation, have been elucidated. The approach has also been applied to the
      synthesis and recovery of silver nanoparticles, but on a larger scale. This new
      approach compares favorably with existing methods as it uses no additional
      organic solvents, has a low-energy demand, and requires no specialist
      surfactants. The new advance here is that by using a colloidal system to prepare
      and support the nanoparticles as a structured solvent, a simple soft purification
      method becomes accessible, which is otherwise impossible with a normal molecular
      solvent.

PMID- 20039605
TI  - In situ time-resolved XAFS study on the formation mechanism of Cu nanoparticles
      using poly(N-vinyl-2-pyrrolidone) as a capping agent.
AB  - The formation mechanism of copper nanoparticles (NPs) using poly(N-vinyl-2
      pyrrolidone) (PVP) as a capping agent was investigated by measurements of X-ray
      diffraction (XRD), transmission electron microscopy (TEM), in situ time-resolved
      X-ray adsorption fine structure (XAFS) analysis, in situ UV-vis spectroscopy, and
      an indicator method. XAFS analyses, in combination with TEM observations and the
      indicator method, revealed that the stable intermediates such as Cu(OH)(2) and
      Cu(+)-PVP intermediate were formed during an induction period of nucleation of Cu
      NPs, which play a critical role in the Cu NP formation. Our results suggest that
      the PVP capping agent is important not only to protect NPs from overgrowth and
      aggregation but also to control the reaction kinetics of NP formation.

PMID- 20039606
TI  - Regioselective synthesis of heterocycles containing nitrogen neighboring an
      aromatic ring by reductive ring expansion using diisobutylaluminum hydride and
      studies on the reaction mechanism.
AB  - A systematic investigation of the reductive ring-expansion reaction of cyclic
      ketoximes fused to aromatic rings with diisobutylaluminum hydride (DIBALH) is
      described. This reaction regioselectively afforded a variety of five- to eight
      membered bicyclic heterocycles or tricyclic heterocycles containing nitrogen
      neighboring an aromatic ring, including indoline, 1,2,3,4,5,6
      hexahydrobenz[b]azocine, 3,4-dihydro-2H-benzo[b][1,4]oxazine, 2,3,4,5
      tetrahydrobenzo[b][1,4]thiazepine, 1,2,3,4,5,6-hexahydroazepino[3,2-b]indole,
      2,3,4,5-tetrahydro-1H-benzothieno[2,3-b]azepine, 2,3,4,5-tetrahydro-1H
      benzothieno[3,2-b]azepine, 5,6-dihydrophenanthridine, and 5,6,11,12
      tetrahydrodibenz[b, f]azocine. The reaction mechanism leading to the
      rearrangement was investigated on the basis of the restricted Becke three
      parameter plus Lee-Yang-Parr (B3LYP) density functional theory (DFT) with the 6
      31G (d) basis set. It was found that the reaction proceeds through a three
      centered transition state via a stepwise mechanism because the potential energy
      curve along the intrinsic reaction coordinate (IRC) had two maxima (saddle
      points; TS1 and TS2) and the partial phenonium cation intermediate C. In addition
      to cyclic ketoximes fused to aromatic rings, the reactions of various cyclic and
      acyclic ketoximes were examined to investigate preference of migrating group. It
      was found that the more electron-rich group migrated preferentially to give the
      corresponding secondary amines.

PMID- 20039607
TI  - Modulation of excited-state intramolecular proton transfer reaction of 1-hydroxy
      2-naphthaldehyde in different supramolecular assemblies.
AB  - The excited-state intramolecular proton transfer (ESIPT) reaction of 1-hydroxy-2
      naphthaldehyde (HN12) has been studied within the interior of the supramolecular
      assemblies of alpha-, beta-, and gamma-cyclodextrins (CD) and biomimicking
      environments of ionic (SDS) and non-ionic (TW-20) micelles. Fluorescence
      measurements are used to investigate the effect of various supramolecular
      assemblies on the ESIPT reaction by monitoring the large Stokes-shifted tautomer
      emission of HN12. Enhanced tautomer emission in the microencapsulated state
      predicts favorable ESIPT reaction in the supramoleuclar assemblies. Benesi
      Hildebrand plots have been employed to ascertain that the stoichiometric ratios
      of the complexes formed between HN12 and CDs are 1:2, 1:1, and 1:1 for alpha-,
      beta-, and gamma-CD, respectively. The binding constants (K(1)) and free-energy
      change (DeltaG) for inclusion complexation are also determined from the
      linearized Benesi-Hildebrand plots. Steady-state fluorescence anisotropy, REES,
      excitation anisotropy, and fluorescence lifetime measurements are in line with
      other experimental findings. Differential action of urea on SDS and TW-20-bound
      probe has also been investigated.

PMID- 20039609
TI  - Intermetallics as novel supports for Pt monolayer O2 reduction electrocatalysts:
      potential for significantly improving properties.
AB  - We report on a new class of core-shell electrocatalysts for the oxygen-reduction
      reaction. These electrocatalysts comprise a Pt monolayer shell and ordered
      intermetallic compounds cores and have enhanced activity and stability compared
      with conventional ones. These advantages are derived from combining the unique
      properties of Pt monolayer catalysts (high activity, low metal content) and of
      the intermetallic compounds (high stability and, possibly, low price). This
      method holds excellent potential for creating efficient fuel cell
      electrocatalysts.

PMID- 20039608
TI  - Understanding organic film behavior on alloy and metal oxides.
AB  - Native oxide surfaces of stainless steel 316L and Nitinol alloys and their
      constituent metal oxides, namely nickel, chromium, molybdenum, manganese, iron,
      and titanium, were modified with long chain organic acids to better understand
      organic film formation. The adhesion and stability of films of
      octadecylphosphonic acid, octadecylhydroxamic acid, octadecylcarboxylic acid, and
      octadecylsulfonic acid on these substrates were examined in this study. The films
      formed on these surfaces were analyzed by diffuse reflectance infrared Fourier
      transform spectroscopy, contact angle goniometry, atomic force microscopy, and
      matrix-assisted laser desorption ionization mass spectrometry. The effect of the
      acidity of the organic moiety and substrate composition on the film
      characteristics and stability is discussed. Interestingly, on the alloy surfaces,
      the presence of less reactive metal sites does not inhibit film formation.

PMID- 20039610
TI  - Persistent, well-defined, monodisperse, pi-conjugated organic nanoparticles via G
      quadruplex self-assembly.
AB  - Several oligo(p-phenylene-vinylene) oligomers capped with a guanosine or a
      guanine moiety have been prepared via a palladium-catalyzed cross-coupling
      reaction. Their self-assembly, in both the absence and presence of alkaline
      salts, has been studied by means of different techniques in solution (NMR, MS, UV
      vis, CD, fluorescence), solid state (X-ray diffraction), and on surfaces (STM,
      AFM). When no salt is added, these pi-conjugated molecules self-associate in a
      mixture of hydrogen-bonded oligomers, among which the G-quartet structure may be
      predominant if the steric hindrance around the guanine base becomes important. In
      contrast, in the presence of sodium or potassium salts, well-defined assemblies
      of eight functional molecules (8mers) can be formed selectively and
      quantitatively. In these assemblies, the pi-conjugated oligomers are maintained
      in a chirally tilted (J-type) stacking arrangement, which is manifested by
      negative Cotton effects, small bathochromic absorption and emission shifts, and
      fluorescence enhancements. Furthermore, these self-assembled organic
      nanostructures, approximately 1.5-2.0 nm high and 8.5 nm wide, exhibit an
      extraordinary stability to temperature or concentration changes in apolar media,
      and they can be transferred and imaged over solid substrates as individual
      nanoparticles, showing no significant dissociation or further aggregation.

PMID- 20039611
TI  - Actinide redox-active ligand complexes: reversible intramolecular electron
      transfer in U(dpp-BIAN)2/U(dpp-BIAN)2(THF).
AB  - Actinide complexes of the redox-active ligand (dpp-BIAN)(2-) (dpp-BIAN = 1,2
      bis(2,6-diisopropylphenylimino)acenaphthylene), U(dpp-BIAN)(2) (1), U(dpp
      BIAN)(2)(THF) (1-THF), and Th(dpp-BIAN)(2)(THF) (2-THF), have been prepared.
      Solid-state magnetic and single-crystal X-ray data for complex 1 indicate a
      ground-state U(IV)-pi*(4) configuration, whereas a (dpp-BIAN)(2-)-to-uranium
      electron transfer occurs for 1-THF, resulting in a U(III)-pi*(3) ground
      configuration. The solid-state magnetic data also indicate that interconversion
      between the two forms of the complex is possible, limited only by the ability of
      tetrahydrofuran (THF) vapor to penetrate the solid upon cooling of the sample. In
      contrast to those in the solid state, spectroscopic data acquired in THF indicate
      only the presence of the U(IV)-pi*(4) form for 1-THF in solution, evidenced by
      electronic absorption spectra and by measurement of the solution magnetic moment
      in THF-d(8) using the Evans method. Also reported is the electrochemistry of the
      complexes collected in CH(2)Cl(2), CF(3)C(6)H(5), and THF. As expected from the
      solution spectroscopic data, only small differences are observed in half-wave
      potentials of ligand-based processes in the presence of THF, consistent with the
      solution U(IV)-pi*(4) configuration of the complexes in all cases. Density
      functional theory calculations were undertaken for complexes 1 and 1-THF to
      determine if intrinsic energetic or structural factors underlie the observed
      charge-transfer process. While the calculated optimized geometries agree well
      with experimental results, it was not possible to arrive at a convergent solution
      for 1-THF in the U(III)-pi*(3) configuration. However, perturbations in the
      orbital energies in 1 versus 1-THF for the U(IV)-pi*(4) configuration do point to
      a diminished highest occupied molecular orbital-lowest unoccupied molecular
      orbital energy gap in 1-THF, consistent with the solid-state magnetic data. These
      results represent the first example of a stable and well-defined, reversible
      intramolecular electron transfer in an actinide complex with redox-active
      ligands.

PMID- 20039612
TI  - A photochemical precursor for carbon monoxide release in aerated aqueous media.
AB  - Interest in therapeutic applications of carbon monoxide release to physiological
      targets has led us to explore a photochemical strategy for such CO delivery.
      Here, we describe the photoactivated carbon monoxide releasing moiety
      (photoCORM), W(CO)(5)(TPPTS)(3-) (1), an air-stable, water-soluble tungsten(0)
      carbonyl complex of the trianionic ligand tris(sulphonatophenyl)phosphine. Near
      UV photolysis of 1 in an aqueous buffer solution leads to the high quantum yield
      release of a single CO, the formation of which has been verified by three
      analytical methodologies. Furthermore, in aerated media, additional CO is slowly
      released from the W(CO)(4)(H(2)O)(TPPTS)(3-) photoproduct owing to autoxidation
      of the tungsten center. Thus, 1 serves as a carbon monoxide releasing moiety both
      in the primary photochemical reaction and in the secondary reactions of the
      initially formed photoproduct. The three methodologies for quantifying CO release
      under these physiologically relevant conditions are also described.

PMID- 20039613
TI  - Thioester hydrolysis promoted by a mononuclear zinc complex.
AB  - The mononuclear zinc complex [(bpta)Zn](ClO(4))(2).0.5H(2)O promotes the
      hydrolysis of the thioester PhCH(OH)C(O)SCD(3) when dissolved in CH(3)CN:H(2)O
      (50:50 buffered at pH 9.0). This reaction results in the formation of a mixture
      of CD(3)SH and a zinc thiolate complex, the latter of which can be protonated to
      generate additional CD(3)SH. Kinetic studies revealed an overall second-order
      reaction with an activation energy that is similar to that found for aqueous OH(
      ) promoted thioester hydrolysis. These studies represent the first investigation
      of chemistry relevant to that occurring in the monozinc-containing form of human
      glyoxalase II.

PMID- 20039614
TI  - Oxazolone cycloadducts as heterocyclic scaffolds for alkaloid construction:
      synthesis of (+/-)-2-epi-pumiliotoxin C.
AB  - Intramolecular Diels-Alder cycloaddition of N-substituted oxazolone triene I
      allows direct entry to the functionalized octahydroquinoline II. Further
      manipulation of this framework by stereo- and regioselective introduction of the
      5-methyl substituent, followed by excision of the carbamate, yields (+/-)-2-epi
      pumiliotoxin C.

PMID- 20039615
TI  - Excited state luminescence of multi-(5-phenyl-1,3,4-oxadiazo-2-yl)benzenes in an
      electron-donating matrix: exciplex or electroplex?
AB  - Multi-(5-phenyl-1,3,4-oxadiazo-2-yl)benzenes show emission in organic solvents
      from ultraviolet to blue (339-447 nm). The reduction potentials E(1/2)(red) cover
      a large range of -2.11 V for 2,5-diphenyl-1,3,4-oxadiazole to -0.76 V for
      1,2,3,4,5,6-hexa(5-phenyl-1,3,4-oxadiazo-2-yl)benzene. An unexpectedly wide
      spectral range of the oxadiazole (OXD) exciplex emissions in PVK is observed,
      ranging from 406 to 603 nm. The OXDs also exhibit similar electroluminescence
      (EL) when blended into polyvinylcarbazole (PVK). A linear correlation between the
      lambda(max) of the electroluminescence and photoluminescence is observed,
      implying that the emission mechanisms in both processes are similar. In addition,
      the linear correlation between the E(1/2)(red) versus lambda(max) of EL (eV)
      reflected that the term of the charge-transfer configuration of the contact
      electron-hole pair plays a major role in the exciplex emission. The exciplex EL
      of 1,2,5-tri(5-phenyl-1,3,4-oxadiazo-2-yl)benzene (5) could be as high as 1.0
      cd/A. Since the exciplex emission usually has a large Stokes shift, this provides
      a window for us to generate duo emissions for near white light EL with high
      efficiency. Among the devices we tried, the device of PVK/2-tert-butylphenyl-5
      biphenyl-1,3,4-oxadiazole/5/2,5,8,11-tetra-tert-butylperylene (100:40:40:4) gave
      EL with good current efficiency of 1.63 cd/A.

PMID- 20039617
TI  - Synthesis of alpha,omega-diarylbutadienes and -hexatrienes via decarboxylative
      coupling of cinnamic acids with vinyl bromides under palladium catalysis.
AB  - Readily available cinnamic acid derivatives such as ferulic acid couple with beta
      bromostyrenes and 1-bromo-4-phenylbutadiene under palladium catalysis accompanied
      by decarboxylation to produce the corresponding alpha,omega-diarylbutadienes and 
      hexatrienes, respectively. Some of the products exhibit solid-state fluorescence.

PMID- 20039616
TI  - Guanine nucleotides: base-centered and phosphate-centered valence-bound radical
      anions in aqueous solution.
AB  - To explore the nature of electron attachment to the guanine-centered DNA
      fragments in the presence of a polarizable medium, theoretical investigation of
      electron attachment to the guanine-related DNA single-strand fragments
      deoxyguanosine-3'-monophosphate (dGp), deoxyguanosine-5'-monophosphate (pdG), and
      deoxyguanosine-3',5'-diphosphate (pdGp) were performed using density functional
      theory with the polarizable continuum model. The electron distributions for the
      radical anions of pdGp in aqueous solution are extraordinarily different from
      those in the gas phase. In solution, the excess electron can covalently bind
      either to the base (forming pdG(*-)p) or to the 3'-phosphate in the radical anion
      (forming pdGp(*-)). The significant electron detachment energies found for these
      radical anions suggest that both pdG(*-)p and pdGp(*-) are electronically stable
      species in aqueous solution and are expected to be initiators in electron
      attachment-induced DNA damage in nature. In the presence of the polarizable
      medium, the base-centered radical anion pdG(*-)p is more stable than the
      phosphate-centered structure. By comparison with electron attachment to the
      monophosphated nucleotide models pdG and dGp, the existence of the phosphate
      centered radical pdGp(*-) in pdGp is attributed to the cooperative influence of
      the two phosphate groups and the polarizable medium.

PMID- 20039618
TI  - Steric control of alpha- and beta-alkylation of azulenone intermediates in a
      guanacastepene a synthesis.
AB  - The origins of different stereoselectivities observed experimentally in the
      alkylations of azulenone precursors in the guanacastepene A synthesis have been
      determined through density functional theory investigations. The optimized
      transition structures of methylation of two different guanacastepene A precursors
      show that steric effects, rather than torsional factors that often determine such
      stereoselectivities, dictate the preferred products observed.

PMID- 20039619
TI  - Temperature dependence of conjugation of amyloid beta protein on the surfaces of
      gold colloidal nanoparticles.
AB  - The absorption spectrum of the amyloid beta 1-40 peptide (Abeta(1-40)) conjugated
      to gold colloidal suspension of 15, 20, 30, and 40 nm size were examined under
      temperature ranging from 5 to 50 degrees C. As the pH was externally altered
      repetitively between pH 4 and 10, Abeta(1-40)-coated 20 nm gold colloid
      nanoparticles exhibited a reversible color change at the entire temperature range
      tested in this study except for 5 +/- 0.2 degrees C. This reversible change may
      be due to the fact that hydrophilic Abeta(1-40) evolves between a three
      dimensional network containing mainly beta-sheet and alpha-helices, and an
      intermediate of this process implies a reversible step reported as initiation of
      the fibrillogenesis in Alzheimer's disease. When other nanosize particles were
      investigated, Abeta(1-40)-coated 30 and 40 nm colloids exhibited the reversible
      color change when temperature was lowered to 18 +/- 0.2 and 6 +/- 0.2 degrees C,
      respectively. This specific and unique size and temperature dependence in
      reversible color change strongly suggests that the noncovalent intrinsic
      intermolecular potential formed between the nanocolloidal surface and each
      Abeta(1-40) monomer conjugated at the surface drives the process.

PMID- 20039620
TI  - Potential of mean force of association of large hydrophobic particles: toward the
      nanoscale limit.
AB  - The potentials of mean force (PMFs) were determined, in both water with the TIP3P
      water model and in vacuo, for systems involving formation of nonpolar dimers
      composed of bicyclooctane, adamantane (both an all-atom model and a sphere with
      the radius of 3.4 A representing adamantane), and fullerene, respectively. A
      series of umbrella-sampling molecular dynamics simulations with the AMBER force
      field were carried out for each pair under both environmental conditions. The
      PMFs were calculated by using the weighted histogram analysis method. The results
      were compared with our previously determined PMF for neopentane. The shape of the
      PMFs for dimers of all four nonpolar molecules is characteristic of hydrophobic
      interactions with contact and solvent-separated minima and desolvation maxima.
      The positions of all these minima and maxima change with the size of the nonpolar
      molecule; for larger molecules they shift toward larger distances. Comparison of
      the PMFs of the bicyclooctane, adamantane, and fullerene dimers in water and in
      vacuo shows that hydrophobic interactions in each dimer are different from that
      for the dimer of neopentane. Interactions in the bicyclooctane, adamantane, and
      fullerene dimers are stronger in vacuo than in water. These dimers cannot be
      treated as classical, spherical, hydrophobic objects. The solvent contribution to
      the PMF was also computed by subtracting the PMF determined in vacuo from that in
      explicit solvent. The solvent contribution to the PMFs of bicyclooctane,
      adamantane, and fullerene is positive, as opposed to that of neopentane. The
      water molecules in the first solvation sphere of both adamantane and neopentane
      dimers are more ordered as compared to bulk water, with their dipole moments
      pointing away from the surface of the dimers. The average number of hydrogen
      bonds per water molecule in the first hydration shell of adamantane is smaller
      compared to that in bulk water, but this shell is thicker for all-atom adamantane
      than for neopentane or a spherical model of adamantane. In the second hydration
      shell, the average number of hydrogen bonds is greater compared to that in bulk
      water only for neopentane and a spherical model of adamantane but not for the all
      atom model. The strength of the hydrophobic interactions shows a linear
      dependence on the number of carbon atoms both in water and in vacuo. Smaller
      nonpolar particles interact more strongly in water than in vacuo. For larger
      molecules, such as bicyclooctane, adamantane and fullerene, the reversed tendency
      is observed.

PMID- 20039621
TI  - Enzyme catalysis by hydrogen bonds: the balance between transition state binding
      and substrate binding in oxyanion holes.
AB  - Oxyanion holes stabilize oxygen anions in transition states. Data have been
      gathered both from enzyme structures and from corresponding structures from the
      Cambridge Crystallographic Database. The two data sets show a striking contrast.
      The small molecule interactions in the Cambridge database optimize hydrogen
      bonding. The enzyme active sites do not. Analyzing the data with the help of DFT
      calculations on theozyme-like models, we conclude that enzymes have not optimized
      binding to the transition state structures in reaction pathways involving
      oxyanion holes, because the best binding arrangement for the anions also
      optimizes binding for the starting materials of the reactions. Instead, enzymes
      arrange the hydrogen bonds so that the oxyanions are stabilized reasonably, but
      suboptimally, in order to avoid overstabilization of the ground state.

PMID- 20039622
TI  - Effects of pressure on the recovery of CO2 by phase transition from a seawater
      system by means of multilayer gas permeable membranes.
AB  - Using seawater doped with sodium bicarbonate and Celgard 2400 gas permeable
      membranes, bicarbonate ion disproportionates to carbon dioxide and carbonate when
      gaseous carbon dioxide is first removed from the seawater solution by diffusion
      through gas permeable membranes at elevated water pressures. The permeability of
      CO(2) by phase transition from bicarbonate solutions at pressures above 100 psi
      is only possible due to the use of multiple gas permeable membrane layers. The
      multiple layers minimize water permeability at pressures below and above the
      Young-Laplace bubble point of single membrane layers, however the gas
      permeability efficiency and rate are greatly decreased.

PMID- 20039623
TI  - Low-energy electron attachment to the dichlorodifluoromethane (CCl2F2) molecule.
AB  - Results from a joint experimental study of electron attachment to
      dichlorodifluoromethane (CCl(2)F(2)) molecules in the gas phase are reported. In
      a high resolution electron beam experiment involving two versions of the laser
      photoelectron attachment method, the relative cross section for formation of the
      dominant anion Cl(-) was measured over the energy range 0.001-1.8 eV at the gas
      temperature T(G) = 300 K. It exhibits cusp structure at thresholds for
      vibrational excitation of the nu(3)(a(1)) mode due to interaction with the
      attachment channels. With reference to the thermal attachment rate coefficient
      k(T = 300 K) = 2.2(8) x 10(-9) cm(3) s(-1) (fitted average from several data), a
      new highly resolved absolute attachment cross section for T(G) = 300 K was
      determined. Partial cross sections for formation of the anions Cl(-), Cl(2)(-),
      F(-), ClF(-), and CCl(2)F(-) were measured over the range 0-12 eV, using three
      different electron beam experiments of medium energy resolution. The dependence
      of the attachment rate coefficient k(T(e);T(G) = 300 K) on electron temperature
      T(e) was calculated over the range 50-15 000 K, based on a newly constructed
      total cross section for anion formation at T(G) = 300 K. R-matrix calculations
      for Cl(-) production have been carried out for comparison with the experimental
      data. The R-matrix results are in line with the main experimental observations
      and predict the dependence of the DEA cross section on the initial vibrational
      level nu(3)() and on the vibrational temperature. Furthermore, the cross section
      for vibrational excitation of the nu(3) mode has been computed.

PMID- 20039624
TI  - DFT study on the factors determining the enantioselectivity of Friedel-Crafts
      reactions of indole with N-acyl and N-tosylimines catalyzed by BINOL-phosphoric
      acid derivatives.
AB  - DFT methods have been used to study the mechanism and the enantioselectivity of
      the Friedel-Crafts reaction of indoles with acyl and tosyl imides catalyzed by
      BINOL-phosphoric acid catalysts. The results are in excellent agreement with the
      experimental enantioselectivities. The energies of the competing transition
      structures and, thus, the enantioselectivity are rationalized from calculations
      on a model system. We propose a simple model to predict the absolute
      configuration of the products.

PMID- 20039625
TI  - Unimolecular HCl and HF elimination reactions of 1,2-dichloroethane, 1,2
      difluoroethane, and 1,2-chlorofluoroethane: assignment of threshold energies.
AB  - The recombination of CH(2)Cl and CH(2)F radicals generates vibrationally excited
      CH(2)ClCH(2)Cl, CH(2)FCH(2)F, and CH(2)ClCH(2)F molecules with about 90 kcal mol(
      1) of energy in a room temperature bath gas. New experimental data for
      CH(2)ClCH(2)F have been obtained that are combined with previously published
      studies for C(2)H(4)Cl(2) and C(2)H(4)F(2) to define reliable rate constants of
      3.0 x 10(8) (C(2)H(4)F(2)), 2.4 x 10(8) (C(2)H(4)Cl(2)), and 1.9 x 10(8)
      (CH(2)ClCH(2)F) s(-1) for HCl and HF elimination. The product branching ratio for
      CH(2)ClCH(2)F is approximately 1. These experimental rate constants are compared
      to calculated statistical rate constants (RRKM) to assign threshold energies for
      HF and HCl elimination. The calculated rate constants are based on transition
      state models obtained from calculations of electronic structures; the energy
      levels of the asymmetric, hindered, internal rotation were directly included in
      the state counting to obtain a more realistic measure for the density of internal
      states for the molecules. The assigned threshold energies for C(2)H(4)F(2) and
      C(2)H(4)Cl(2) are both 63 +/- 2 kcal mol(-1). The threshold energies for
      CH(2)ClCH(2)F are 65 +/- 2 (HCl) and 63 +/- 2 (HF) kcal mol(-1). These threshold
      energies are 5-7 kcal mol(-1) higher than the corresponding values for C(2)H(5)Cl
      or C(2)H(5)F, and beta-substitution of F or Cl atoms raises threshold energies
      for HF or HCl elimination reactions. The treatment presented here for obtaining
      the densities of states and the entropy of activation from models with asymmetric
      internal rotations with high barriers can be used to judge the validity of using
      a symmetric internal-rotor approximation for other cases. Finally, threshold
      energies for the 1,2-fluorochloroethanes are compared to those of the 1,1
      fluorochloroethanes to illustrate substituent effects on the relative energies of
      the isomeric transition states.

PMID- 20039626
TI  - Microwave-assisted palladium-catalyzed phosphonium coupling of 2(1H)-pyrazinones.
AB  - An expedient route for the synthesis of differently substituted 2(1H)-pyrazinones
      applying a microwave-assisted palladium-catalyzed phosphonium coupling procedure
      is reported. The method has also been successfully extended to some other
      tautomerizable heterocycles for efficient C-C cross-coupling.

PMID- 20039627
TI  - Direct observation of the gas phase reaction of the cyclohexyl radical with
      dioxygen using a distonic radical ion approach.
AB  - Alkylperoxyl radicals are intermediates in the oxidation of hydrocarbons. The
      reactive nature of these intermediates, however, has made them elusive to direct
      observation and isolation. We have employed ion trap mass spectrometry to
      synthesize and characterize 4-carboxylatocyclohexyl radical anions (*C(6)H(10)
      CO(2)(-)) and observe their reactivity in the presence of dioxygen. The resulting
      reaction is facile (k = 1.8 x 10(-10) cm(3) molecule(-1) s(-1) or 30% of
      calculated collision rate) and results in (i) the addition of O(2) to form
      stabilized 4-carboxylatocyclohexylperoxyl radical anions (*OO-C(6)H(10)-CO(2)(
      )), providing the first direct observation of a cyclohexylperoxyl radical, and
      (ii) elimination of HO(2)* and HO* radicals consistent with recent laser-induced
      fluorescence studies of the reaction of neutral cyclohexyl radicals with O(2).
      Electronic structure calculations at the B3LYP/6-31+G(d) level of theory reveal
      viable pathways for the observed reactions showing that formation of the peroxyl
      radical is exothermic by 37 kcal mol(-1) with subsequent transition states as low
      as -6.6 kcal mol(-1) (formation of HO(2)*) and -9.1 kcal mol(-1) (formation of
      HO*) with respect to the entrance channel. The combined computational and
      experimental data suggest that the structures of the reaction products correspond
      to cyclohexenes and epoxides from HO(2)* and HO* loss, respectively, while
      alternative pathways leading to cyclohexanone or ring-opened isomers are not
      observed. Activation of the charged peroxyl radical *OO-C(6)H(10)-CO(2)(-) by
      collision induced dissociation also results in the loss of HO(2)* and HO*
      radicals confirming that these products are directly connected to the peroxyl
      radical intermediate.

PMID- 20039628
TI  - Weakly bound carbon-carbon bonds in acenaphthene derivatives and
      hexaphenylethane.
AB  - A class of acenaphthene derivatives is shown to contain weak central carbon
      carbon bonds that may be easily cleaved at high temperatures or even at ambient
      conditions to yield persistent free diradicals. To demonstrate the weak C-C bond
      strength, density functional theory calculations were carried out at several
      levels of theory for both the parent molecules and the diradicals resulting from
      the C-C bond cleavage. To assess the accuracy of the calculations,
      hexaphenylethane was chosen as a model compound due to its similarity with the
      molecules studied here, its great resonance stabilization, and long-standing
      history within the chemistry community. The C-C bond dissociation energy of
      hexaphenylethane was determined to be 11.3 +/- 1.4 kcal/mol using a combination
      of isodesmic reactions and calculations at the M06-2X/6-31+G(d,p) level of
      theory. The types of molecules presented here are proposed as strong
      possibilities for the natural existence of free radicals in young and mature soot
      formed in hydrocarbon combustion.

PMID- 20039631
TI  - DiSpiroXanthene-IndenoFluorene: a new blue emitter for nondoped organic light
      emitting diode applications.
AB  - Through an expedient synthesis, a novel blue emitter, DiSpiroXanthene
      IndenoFluorene (DSX-IF) has been designed and synthesized. DSX-IF possesses good
      morphological and color stability upon heating, has a high quantum yield, and may
      be easily polymerized through anodic oxidation. Small molecule organic light
      emitting diodes (SMOLEDs), using this promising new dixanthene derivative as a
      blue emissive layer, exhibit a maximum luminance of ca. 3800 Cd.m(-2) with a
      luminous efficiency of 1 Cd.A(-1).

PMID- 20039629
TI  - Array-based sensing of normal, cancerous, and metastatic cells using conjugated
      fluorescent polymers.
AB  - A family of conjugated fluorescent polymers was used to create an array for cell
      sensing. Fluorescent conjugated polymers with pendant charged residues provided
      multivalent interactions with cell membranes, allowing the detection of subtle
      differences between different cell types on the basis of cell surface features.
      Highly reproducible characteristic patterns were obtained from different cell
      types as well as from isogenic cell lines, enabling the identification of the
      cell type as well differentiating between normal, cancerous, and metastatic
      isogenic cell types with high accuracy.

PMID- 20039630
TI  - Interconversion between a nonporous nanocluster and a microporous coordination
      polymer showing selective gas adsorption.
AB  - Using reversible polymerization and depolymerization reactions in a single
      crystal state, we achieved a reversible transformation from a nanocluster to a
      coordination polymer. During the interconversion, the structural frameworks
      switched between nonporous hexanuclear clusters and porous double-zigzag chains;
      the magnetic behaviors switched between paramagnetism and metamagnetism,
      respectively. The microporous framework, which had 1D channels 1.9 A x 3.6 A in
      size, exhibited selective gas adsorption of H(2) and CO(2) over N(2).

PMID- 20039632
TI  - Modeling the dissociative hydrolysis of the natural DNA nucleosides.
AB  - Two-dimensional PCM-B3LYP/6-31+G(d) potential energy surfaces for the hydrolysis
      of the four natural 2'-deoxyribonucleosides (2'-deoxyadenosine, 2'
      deoxyguanosine, 2'-deoxycytidine, and thymidine) are characterized using a model
      that includes both implicit (bulk) solvent effects and (three or four) explicit
      water molecules in the optimization routine. For the first time, the
      experimentally predicted dissociative (S(N)1) mechanism is found to be favored
      over the synchronous (S(N)2) pathway for all nucleosides studied. Due to the
      success of our model in stabilizing the charge-separated intermediates along the
      S(N)1 pathway, it is proposed that the new model presented here is the smallest
      system capable of generating the experimentally predicted oxacarbenium cation
      intermediate. We therefore stress that dissociative mechanisms should be studied
      with methodologies that account for the (bulk) environment in the optimization
      routine, where these effects are often only included as a correction to the
      energy in the current literature. In addition to accounting for charge
      stabilization through implicit solvation, nucleophile activation and leaving
      group stabilization should also be explicitly introduced into the model to
      further stabilize the system. Our work also emphasizes the importance of studying
      the Gibbs surface, which in some cases provides a better description of
      chemically important regions of the reaction surface or changes the calculated
      trend in the magnitude of dissociative barriers. In addition, it is proposed that
      the methodology presented in this study can be used to calculate uncatalyzed
      deglycosylation barriers for a range of DNA nucleosides, which when compared to
      the corresponding enzyme-catalyzed reactions, will allow the prediction of the
      rate enhancement (barrier reduction) due to the enzyme.

PMID- 20039634
TI  - Characterization of nucleobase analogue FRET acceptor tCnitro.
AB  - The fluorescent nucleobase analogues of the tricyclic cytosine (tC) family, tC
      and tC(O), possess high fluorescence quantum yields and single fluorescence
      lifetimes, even after incorporation into double-stranded DNA, which make these
      base analogues particularly useful as fluorescence resonance energy transfer
      (FRET) probes. Recently, we reported the first all-nucleobase FRET pair
      consisting of tC(O) as the donor and the novel tC(nitro) as the acceptor. The
      rigid and well-defined position of this FRET pair inside the DNA double helix,
      and consequently excellent control of the orientation factor in the FRET
      efficiency, are very promising features for future studies of nucleic acid
      structures. Here, we provide the necessary spectroscopic and photophysical
      characterization of tC(nitro) needed in order to utilize this probe as a FRET
      acceptor in nucleic acids. The lowest energy absorption band from 375 to 525 nm
      is shown to be the result of a single in-plane polarized electronic transition
      oriented approximately 27 degrees from the molecular long axis. This band
      overlaps the emission bands of both tC and tC(O), and the Forster characteristics
      of these donor-acceptor pairs are calculated for double-stranded DNA scenarios.
      In addition, the UV-vis absorption of tC(nitro) is monitored in a broad pH range
      and the neutral form is found to be totally predominant under physiological
      conditions with a pK(a) of 11.1. The structure and electronic spectrum of
      tC(nitro) is further characterized by density functional theory calculations.

PMID- 20039633
TI  - Matrix metalloproteinase 2 (MMP2) inhibition: DFT and QM/MM studies of the
      deprotonation-initialized ring-opening reaction of the sulfoxide analogue of SB
      3CT.
AB  - (4-Phenoxyphenylsulfonyl)methylthiirane (SB-3CT) is the selective inhibitor of
      matrix metalloproteinase 2 (MMP2). The inhibition mechanism of MMP2 by SB-3CT
      involves C-H deprotonation with concomitant opening of the three-membered
      heterocycle. In this study, the energetics of the deprotonation-induced ring
      opening of (4-phenoxyphenylsulfinyl)methylthiirane, the sulfoxide analogue of SB
      3CT, are examined computationally using DFT and QM/MM calculations. A model
      system, 2-(methylsulfinylmethyl)thiirane, is used to study the stereoelectronic
      and conformational effects of reaction barriers in methanol. For the model system
      in methanol solution (using the polarizable continuum model), the reaction
      barriers range from 17 to 23 kcal/mol with significant stereoelectronic effects.
      However, the lowest barriers of the (R,R) and (S,R) diastereomers are similar.
      Two diastereomers of the sulfoxide analogue of SB-3CT are studied in the active
      site of MMP2 by QM/MM methods with an accurate partial charge fitting procedure.
      The ring-opening reactions of these two diastereomers have similar reaction
      energetics. Both are exothermic from the reactant to the ring-opening product
      (thiolate). The protonation of the thiolate by a water molecule is endothermic in
      both cases. However, the deprotonation/ring-opening barriers in the MMP2 active
      site using QM/MM methods for the (R,R) and (S,R) inhibitions are quite different
      (23.3 and 28.5 kcal/mol, respectively). The TSs identified in QM/MM calculations
      were confirmed by vibrational frequency analysis and following the reaction path.
      The (R,R) diastereomer has a hydrogen bond between the sulfoxide oxygen and the
      backbone NH of Leu191, while the (S,R) has a hydrogen bond between the sulfoxide
      oxygen and a water molecule. The dissimilar strengths of these hydrogen bonds as
      well as minor differences in the TS structures contribute to the difference
      between the barriers. Compared to SB-3CT, both diastereomers of the sulfoxide
      analogue have higher reaction barriers and have less exothermic reaction
      energies. This agrees well with the experiments, where SB-3CT is a more effective
      inhibitor of MMP2 than its sulfoxide analogue.

PMID- 20039636
TI  - Cloning, sequencing, purification, and crystal structure of Grenache (Vitis
      vinifera) polyphenol oxidase.
AB  - The full-length cDNA sequence (P93622_VITVI) of polyphenol oxidase (PPO) cDNA
      from grape Vitis vinifera L., cv Grenache, was found to encode a translated
      protein of 607 amino acids with an expected molecular weight of ca. 67 kDa and a
      predicted pI of 6.83. The translated amino acid sequence was 99%, identical to
      that of a white grape berry PPO (1) (5 out of 607 amino acid potential sequence
      differences). The protein was purified from Grenache grape berries by using
      traditional methods, and it was crystallized with ammonium acetate by the hanging
      drop vapor diffusion method. The crystals were orthorhombic, space group C222(1).
      The structure was obtained at 2.2 A resolution using synchrotron radiation using
      the 39 kDa isozyme of sweet potato PPO (PDB code: 1BT1 ) as a phase donor. The
      basic symmetry of the cell parameters (a, b, and c and alpha, beta, and gamma) as
      well as in the number of asymmetric units in the unit cell of the crystals of
      PPO, differed between the two proteins. The structures of the two enzymes are
      quite similar in overall fold, the location of the helix bundles at the core, and
      the active site in which three histidines bind each of the two catalytic copper
      ions, and one of the histidines is engaged in a thioether linkage with a cysteine
      residue. The possibility that the formation of the Cys-His thioether linkage
      constitutes the activation step is proposed. No evidence of phosphorylation or
      glycoslyation was found in the electron density map. The mass of the crystallized
      protein appears to be only 38.4 kDa, and the processing that occurs in the grape
      berry that leads to this smaller size is discussed.

PMID- 20039635
TI  - Residue depletion and tissue-plasma correlation of methyl-3-quinoxaline-2
      carboxylic acid after dietary administration of olaquindox in pigs.
AB  - A residue depletion study was performed to investigate the tissue kinetics and
      tissue-plasma correlation of methyl-3-quinoxaline-2-carboxylic acid (MQCA), the
      marker residue of olaquindox (OLA), in pigs. Twenty-five pigs were randomly
      divided into a test and a control group. The former group was treated with 100
      mg/kg OLA in its feed for 30 consecutive days, and the latter was given blank
      feed for the same period. One control and four treated animals were slaughtered
      at 0.5, 3, 10, 17, and 28 days post-medication. Muscle, liver, kidney, fat, and
      plasma samples were collected and analyzed using the validated high-performance
      liquid chromatography method (HPLC). Results showed that the tissue concentration
      of MQCA in the liver > kidney > fat > muscle, at almost all time points. The half
      lives of MQCA in the muscle, liver, kidney, fat, and plasma were 12, 8, 15, 8,
      and 6 days, respectively. A withdrawal period of 38 days was calculated using the
      statistical method recommended by the European Medical Evaluation Agency (EMEA).
      Good correlations between tissue and plasma MQCA levels were found in the present
      study with correlation coefficients of more than 0.92. These correlations would
      be helpful in the routine monitoring of OLA in porcine tissues, without
      sacrificing the animals.

PMID- 20039638
TI  - Lewis Acid catalyzed three-component hetero-Diels-alder (povarov) reaction of N
      arylimines with strained norbornene-derived dienophiles.
AB  - Generally, the hetero-Diels-Alder reaction (Povarov reaction) of N-arylimine
      dienes are limited to reaction with activated, electron-rich alkenes. However,
      introduction of ring strain in the dienophile, as with moderately strained
      bicyclo[2.2.1]heptenes (norbornene), enables three-component Povarov reaction
      with in situ formed N-arylimines under Lewis acid catalyzed conditions
      (BF(3).OEt(2)). The reactions proceed efficiently with a diverse set of
      commercially available anilines and benzaldehydes, as well as a variety of
      substituted norbornenes. The corresponding tetrahydroquinolines are formed with
      high complexity in a multicomponent fashion and are obtained in good yield and
      high diastereoselectivity. In addition, more reactive ethyl glyoxylate derived
      imines were utilized to achieve faster, room temperature reactions with
      norbornene. In all cases, attack of the N-arylimine dienes occurred exclusively
      from the exo-face of the norbornene ring, but the relative stereochemistry of the
      substituent alpha to the tetrahydroquinoline nitrogen, as well as the
      regioselectivity of reaction, was shown to depend upon subtle substituent effects
      on the aniline precursors. In most cases, a preference for the formation of exo
      exo diastereomeric adducts was observed, but for reactions of ortho- or meta
      substituted anilines, the formation of exo-endo adducts was also observed. These
      observations may be rationalized by two competing mechanistic models, involving
      either a concerted asynchronous [4 + 2]-like mechanism or a stepwise mechanism.

PMID- 20039637
TI  - Binding of perfluorocarboxylates to serum albumin: a comparison of analytical
      methods.
AB  - Perfluorochemicals are globally pervasive contaminants that are persistent,
      bioaccumulative, and toxic. Perfluorocarboxylic acids (PFCAs) with 8-13 carbons
      accumulate in the liver and blood of aquatic organisms; PFCA-protein interactions
      may explain this accumulation pattern. Here, the interactions between PFCAs with
      8-11 carbons and serum albumin are examined using three experimental approaches:
      surface tension titrations, (19)F NMR spectroscopy, and fluorescence
      spectroscopy. Surface tension titrations indicate complex formation at high (mM)
      PFCA concentrations. Secondary association constants ranging from 10(2) to 10(4)
      M(-1) were determined from (19)F NMR titrations at high PFCA:albumin mole ratios.
      Fluorescence measurements indicate that PFCA-albumin interactions alter the
      protein conformation at low PFCA:albumin mole ratios (up to 5:1) and suggest two
      binding classes with association constants around 10(5) and 10(2) M(-1). While
      (19)F NMR and fluorescence provide both qualitative and quantitative information
      about PFCA-albumin interactions, surface tension provides only qualitative
      information. Limitations associated with instrumentation and methods require high
      PFCA concentrations in both surface tension and (19)F NMR experiments; in
      contrast, fluorescence allows for analysis of a wider range of PFCA
      concentrations and PFCA:albumin mole ratios. Results from this study indicate
      that fluorescence, though an indirect method, offers a more comprehensive picture
      of the nature of PFCA-albumin interactions.

PMID- 20039639
TI  - Steady-state electrochemical determination of lipidic nanotube diameter utilizing
      an artificial cell model.
AB  - By exploiting the capabilities of steady-state electrochemical measurements, we
      have measured the inner diameter of a lipid nanotube using Fick's first law of
      diffusion in conjunction with an imposed linear concentration gradient of
      electroactive molecules over the length of the nanotube. Fick's law has been used
      in this way to provide a direct relationship between the nanotube diameter and
      the measurable experimental parameters Deltai (change in current) and nanotube
      length. Catechol was used to determine the Deltai attributed to its flux out of
      the nanotube. Comparing the nanotube diameter as a function of nanotube length
      revealed that membrane elastic energy was playing an important role in
      determining the size of the nanotube and was different when the tube was
      connected to either end of two vesicles or to a vesicle on one end and a pipet
      tip on the other. We assume that repulsive interaction between neck regions can
      be used to explain the trends observed. This theoretical approach based on
      elastic energy considerations provides a qualitative description consistent with
      experimental data.

PMID- 20039640
TI  - Lanostane triterpenes from the fruiting bodies of Ganoderma lucidum and their
      inhibitory effects on adipocyte differentiation in 3T3-L1 Cells.
AB  - Four new lanostane triterpenes, butyl ganoderate A (1), butyl ganoderate B (2),
      butyl lucidenate N (3), and butyl lucidenate A (4), were isolated from the
      fruiting bodies of Ganoderma lucidum together with 14 known compounds (5-18). The
      structures of the new triterpenes were established by extensive spectroscopic
      studies and chemical evidence. In addition, the inhibitory effect of isolated
      compounds on adipocyte differentiation in 3T3-L1 cells was examined.

PMID- 20039641
TI  - Combining asymmetric catalysis with natural product functionalization through
      enantioselective alpha-fluorination.
AB  - An examination into the derivatization of various natural products using newly
      developed alpha-fluorination methodology is disclosed. An activated ketene
      enolate, generated from an acid chloride, is allowed to react with an
      electrophilic fluorine source (NFSi). Quenching the reaction with a nucleophilic
      natural product produces biologically relevant alpha-fluorinated carbonyl
      derivatives of select chemotherapeutics, antibiotics, and other pharmaceuticals.

PMID- 20039642
TI  - Constituents of Trigonostemon chinensis.
AB  - Phytochemical investigation on the stem bark and wood of Trigonostemon chinensis
      led to the isolation of four new dinorditerpenoids, trigonostemons A-D (1, 3, 5,
      6), a new phenanthrenone, trigonostemon E (7), and a new bisindole alkaloid,
      trigonostemon F (8). The structures were established by extensive spectroscopic
      methods. The absolute configurations of 1-6 were determined by X-ray
      crystallography, circular dichroism, quantum chemical TDDFT calculations, and
      chemical transformations. The relative configuration of 8 was confirmed by X-ray
      diffraction analysis.

PMID- 20039643
TI  - Cytotoxic halogenated metabolites from the Brazilian red alga Laurencia
      catarinensis.
AB  - Seven new (1-7) and seven previously reported (8-14) halogenated metabolites were
      isolated from the organic extract of the Brazilian red alga Laurencia
      catarinensis. The structure elucidation and the assignment of the relative
      configurations of the new natural products were based on detailed NMR and MS
      spectroscopic analyses, whereas the structure of metabolite 6 was confirmed by
      single-crystal X-ray diffraction analysis. The absolute configuration of
      metabolite 1 was determined using the modified Mosher's method. The in vitro
      cytotoxicity of compounds 1-14 was evaluated against HT29, MCF7, and A431 cell
      lines.

PMID- 20039644
TI  - Aryl azides formation under mild conditions: a kinetic study in some ionic liquid
      solutions.
AB  - The kinetics of nucleophilic aromatic substitution of three nitrothiophene
      derivatives in different [1-butyl-3-methylimidazolium][N(3)]/ionic liquid binary
      mixtures was studied spectrophotometrically at 298 K. Ionic liquids differing for
      cation structure (imidazolium or pyrrolidinium) and for size, shape, and
      coordination ability of the anion ([BF(4)(-)], [PF(6)(-)], [SbF(6)(-)], and
      [NTf(2)(-)]) were used. Furthermore, in order to have a comparison with
      conventional organic solvents, the target reaction was also carried out in DMF
      solution at increasing concentration of NaN(3) or [bmim][N(3)]. Data collected
      show that the reaction occurs faster in DMF than in ionic liquid solution.
      Furthermore, as a consequence of the ability of all solvent media to favor the
      leaving group departure, a simple linear dependence of the pseudo-first-order
      kinetic constant from nucleophile concentration was detected. The results of this
      kinetic investigation once more underline that ionic liquids are able to exert
      peculiar effects that can be understood also considering their three-dimensional
      organization.

PMID- 20039645
TI  - O2-dependent aliphatic carbon-carbon bond cleavage reactivity in a Ni(II) enolate
      complex having a hydrogen bond donor microenvironment; comparison with a
      hydrophobic analogue.
AB  - A mononuclear Ni(II) complex having an acireductone type ligand, and supported by
      the bnpapa (N,N-bis((6-neopentylamino-2-pyridyl)methyl)-N-((2
      pyridyl)methyl)amine) ligand, [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4) (14), has
      been prepared and characterized by elemental analysis, (1)H NMR, FTIR, and UV
      vis. To gain insight into the (1)H NMR features of 14, the air stable analogue
      complexes [(bnpapa)Ni(CH(3)C(O)CHC(O)CH(3))]ClO(4) (16) and
      [(bnpapa)Ni(ONHC(O)CH(3))]ClO(4) (17) were prepared and characterized by X-ray
      crystallography, (1)H NMR, FTIR, UV-vis, mass spectrometry, and solution
      conductivity measurements. Compounds 16 and 17 are 1:1 electrolyte species in
      CH(3)CN. (1)H and (2)H NMR studies of 14, 16, and 17 and deuterated analogues
      revealed that the complexes having six-membered chelate rings for the exogenous
      ligand (14 and 16) do not have a plane of symmetry within the solvated cation and
      thus exhibit more complicated (1)H NMR spectra. Compound 17, as well as other
      simple Ni(II) complexes of the bnpapa ligand (e.g.,
      [(bnpapa)Ni(ClO(4))(CH(3)CN)]ClO(4) (18) and [(bnpapaNi)(2)(mu-Cl)(2)](ClO(4))(2)
      (19)), exhibit (1)H NMR spectra consistent with the presence of a plane of
      symmetry within the cation. Treatment of [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4)
      (14) with O(2) results in aliphatic carbon-carbon bond cleavage within the
      acireductone-type ligand and the formation of [(bnpapa)Ni(O(2)CPh)]ClO(4) (9),
      benzoic acid, benzil, and CO. Use of (18)O(2) in the reaction gives high levels
      of incorporation (>80%) of one labeled oxygen atom into 9 and benzoic acid. The
      product mixture and level of (18)O incorporation in this reaction is different
      than that exhibited by the analogue supported the hydrophobic 6-Ph(2)TPA ligand,
      [(6-Ph(2)TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO(4) (2). We propose that this difference is
      due to variations in the reactivity of bnpapa- and 6-Ph(2)TPA-ligated Ni(II)
      complexes with triketone and/or peroxide species produced in the reaction
      pathway.

PMID- 20039647
TI  - From peptides to their alternating ester-urea analogues: synthesis and influence
      of hydrogen bonding motif and stereochemistry on aggregation.
AB  - Peptide-mimicking scaffolds with an incorporated ester-urea motif, replacing two
      adjacent amide residues, were synthesized and their aggregation behavior was
      studied in dependence of hydrogen bonding sites as well as backbone
      stereochemistry. Two oligomer series containing either 50% or 100% ester-urea
      units and either all-(l) or (d)-alt-(l) backbone configuration were prepared via
      ester and amide couplings, using a divergent/convergent exponential growth
      strategy. Their aggregation behavior in organic solution was investigated by
      means of concentration-dependent NMR spectroscopy and compared to the parent
      peptide series. Interestingly, the naturally occurring peptide scaffold exhibits
      the largest tendency to associate in combination with the strongest difference in
      aggregation behavior between all-(l) and (d)-alt-(l) backbone stereochemistry.
      With increasing incorporation of the ester-urea motif the aggregation strength
      decreases and become much less dependent on the backbone configuration. The
      obtained structure-aggregation relationships reveal the importance of the
      commensurability and multivalency of hydrogen bonding sites as well as
      conformational restriction for peptide association and should hence aid the
      design of peptide mimics, such as beta-sheet breakers or gelators.

PMID- 20039646
TI  - Modification of loop 1 affects the nucleotide binding properties of Myo1c, the
      adaptation motor in the inner ear.
AB  - Myo1c is one of eight members of the mammalian myosin I family of actin
      associated molecular motors. In stereocilia of the hair cells in the inner ear,
      Myo1c presumably serves as the adaptation motor, which regulates the opening and
      closing of transduction channels. Although there is conservation of sequence and
      structure among all myosins in the N-terminal motor domain, which contains the
      nucleotide- and actin-binding sites, some differences include the length and
      composition of surface loops, including loop 1, which lies near the nucleotide
      binding domain. To investigate the role of loop 1, we expressed in insect cells
      mutants of a truncated form of Myo1c, Myo1c(1IQ), as well as chimeras of
      Myo1c(1IQ) with the analogous loop from other myosins. We found that replacement
      of the charged residues in loop 1 with alanines or the whole loop with a series
      of alanines did not alter the ATPase activity, transient kinetics properties, or
      Ca(2+) sensitivity of Myo1c(1IQ). Substitution of loop 1 with that of the
      corresponding region from tonic smooth muscle myosin II (Myo1c(1IQ)-tonic) or
      replacement with a single glycine (Myo1c(1IQ)-G) accelerated the release of ADP
      from A.M 2-3-fold in Ca(2+), whereas substitution with loop 1 from phasic muscle
      myosin II (Myo1c(1IQ)-phasic) accelerated the release of ADP 35-fold. Motility
      assays with chimeras containing a single alpha-helix, or SAH, domain showed that
      Myo1c(SAH)-tonic translocated actin in vitro twice as fast as Myo1c(SAH)-WT and 3
      fold faster than Myo1c(SAH)-G. The studies show that changes induced in Myo1c via
      modification of loop 1 showed no resemblance to the behavior of the loop donor
      myosins or to the changes previously observed with similar Myo1b chimeras.

PMID- 20039648
TI  - Oxovanadium(IV) cyclam and bicyclam complexes: potential CXCR4 receptor
      antagonists.
AB  - Metal complexation can have a major influence on the antiviral and coreceptor
      binding properties of cyclam and bicyclam macrocycles. We report the synthesis of
      the vanadyl cyclam complexes [V((IV))O(cyclam)SO(4)] (1) and
      [V((IV))O(cyclam)Cl]Cl (2) and the analogous xylylbicyclam sulfato (3) and
      chlorido (4) complexes. The X-ray crystal structures of 1.1.33CH(3)OH and
      2.CH(3)OH.1.5H(2)O show short V=O bonds (1.6093(19) and 1.599(3) A, respectively)
      with monodentate sulfate H-bonded to ring NH groups for 1, but a long V-Cl bond
      (2.650(12) A) for 2. The solid-state structures of 3 and 4 were compared to those
      of 1 and 2 using vanadium K-edge extended X-ray absorption fine structure (EXAFS)
      data. These suggested that complex 4 was oligomeric and contained bridging
      chlorido ligands. Electron paramagnetic resonance (EPR) studies suggested that
      the SO(4)(2-) (from 1) and Cl(-) (from 2) ligands are readily substituted by
      water in solution, whereas these remain partially bound for the V(IV)
      xylylbicyclam complexes 3 and 4. The vanadyl xylylbicyclam complexes were highly
      active against HIV-1 (III(B)) and HIV-2 (ROD) strains with IC(50) values in the
      range 1-5 microM for 3 and 0.1-0.3 microM for 4; in contrast the vanadyl cyclam
      complexes 1 and 2 were inactive. The factors that contribute to the activity of
      these complexes are discussed. Studies of vanadyl cyclam docked into a model of
      the human CXCR4 coreceptor revealed that the coordination of vanadium to the
      carboxylate of Asp171 may be accompanied by H-bonding to the macrocycle and an
      attractive V=O...H interaction involving the backbone Trp195 alpha-carbon proton
      of CXCR4. In addition, hydrophobic interactions with Trp195 are present. Both
      ring configuration and the xylyl linker may play roles in determining the higher
      activity of the bicyclam complexes.

PMID- 20039649
TI  - Slow relaxation processes and single-ion magnetic behaviors in dysprosium
      containing complexes.
AB  - A series of one-dimensional complexes [Ln(L(1))(3)(HOCH(2)CH(2)OH)](n) (L(1) = 2
      furoate anion; Ln = Nd (1), Sm (2), Gd (3), Tb (4), Dy (5), Er (6)) have been
      synthesized. The complexes were crystallized in the monoclinic space group
      P2(1)/c and show a chain-like structure determined by single-crystal X-ray
      diffraction. Magnetic properties indicate that carboxyl group of 2-furoate
      mediates different magnetic couplings in light and heavy rare earth complexes,
      namely, antiferromagnetic interaction between light rare earth ions and
      ferromagnetic interaction between heavy ones. Noticeably, complex 5 displays a
      strong frequency dependence of alternating current (AC) magnetic properties.
      Further magnetic studies show a distribution of a single relaxation process in 5.
      While 1,10-phenanthroline and phthalate anion (L(2)) were employed,
      [Dy(2)(L(2))(6)(H(2)O)](n) (7) was isolated by hydrothermal reactions and
      characterized magnetically. Research results also show the frequency dependence
      of AC magnetic susceptibilities, although the phthalate anions mediate
      antiferromagnetic coupling between Dy(III) ions. Further magnetic investigation
      of a neutral mononuclear complex with the formula [Dy(TTA)(3)(L(3))] (8) (TTA = 2
      thenoyltrifluoroacetonate; L(3) = 4,5-pinene bipyridine) suggests that the single
      ion magnetic behavior originates the slow relaxation of Dy(III)-containing
      complexes.

PMID- 20039650
TI  - Intramolecular pi-pi stacking interactions in 2-substituted N,N
      dibenzylaziridinium ions and their regioselectivity in nucleophilic ring-opening
      reactions.
AB  - The ring opening of 2-substituted N,N-dibenzylaziridinium ions by bromide is
      known to occur exclusively at the substituted aziridine carbon atom via an S(N)2
      mechanism, whereas the opposite regioselectivity has been observed as the main
      pathway for ring opening by fluoride. Similarly, the hydride-induced ring opening
      of 2-substituted N,N-dibenzylaziridinium ions has been shown to take place solely
      at the less hindered position. To gain insight into the main factors causing this
      difference in regioselectivity, a thorough and detailed computational analysis
      was performed on the hydride- and halide-induced ring openings of 1-benzyl-1
      (alpha-(R)-methylbenzyl)-2(S)-(phenoxymethyl)aziridinium bromide. Intramolecular
      pi-pi stacking interactions in the aziridinium system were investigated at a
      range of levels that enable a proper description of dispersive interactions; a T
      stacking conformer was found to be the most stable. Ring-opening mechanisms were
      investigated with a variety of DFT and high level ab initio methods to test the
      robustness of the energetics along the pathway in terms of the electronic level
      of theory. The necessity to utilize explicit solvent molecules to solvate halide
      ions was clearly shown; the potential energy surfaces for nonsolvated and
      solvated cases differed dramatically. It was shown that in the presence of a
      kinetically viable route, product distribution will be dictated by the
      energetically preferred pathway; this was observed in the case of hard
      nucleophiles (both hydride donors and fluoride). However, for the highly
      polarizable soft nucleophile (bromide), it was shown that in the absence of a
      large energy difference between transition states leading to competing pathways,
      the formation of the thermodynamic product is likely to be the driving force.
      Distortion/interaction analysis on the transition states has shown a considerable
      difference in interaction energies for the solvated fluoride case, pointing to
      the fact that sterics plays a major role in the outcome, whereas for the bromide
      this difference was insignificant, suggesting bromide is less influenced by the
      difference in sterics.

PMID- 20039651
TI  - Anomalous hardening behavior of a calcium phosphate bone cement.
AB  - In this work, an anomalous microscopic and macroscopic behavior during the
      hardening process of a calcium phosphate cement, based on anhydrous dicalcium
      phosphate, was observed. Indeed, the standard compressive strength measurements
      provided completely unexpected results, which encouraged a deeper investigation
      by means of X-ray diffraction, Fourier transform infrared spectroscopy, and
      scanning electron and atomic force microscopies. The energy dispersive X-ray
      diffraction mode was preferred to the conventional angular dispersive one, the
      former being particularly suitable for the real-time studies, allowing us to
      follow the hardening process in situ and to confirm that the investigated cement
      undergoes a long-time crystallization much more complex than expected. Indeed,
      the sequence of diffraction patterns exhibited anomalous intensity modulations
      (corresponding to structural changes taking place upon hardening) being
      consistent, and even in phase, with the variations of the compressive strength.
      These anomalous intensity modulations were confirmed also by the in situ time
      resolved Fourier transform infrared spectroscopy. The explanation of the
      anomalous behavior was given by means of a multiscale approach correlating the
      microscopic (structural) and macroscopic (compressive strength) properties. In
      perspective, this finding may be interesting not only from the fundamental
      materials science point of view, but also for novel applications. For example, it
      might be utilized as an "intrinsic bioreactor", playing the role of stimulator of
      cellular proliferation by exerting stresses due to its alternative contracting
      and expanding internal forces on the tissues.

PMID- 20039652
TI  - Lanthanide phytanates: liquid-crystalline phase behavior, colloidal particle
      dispersions, and potential as medical imaging agents.
AB  - Lanthanide salts of phytanic acid, an isoprenoid-type amphiphile, have been
      synthesized and characterized. Elemental analysis and FTIR spectroscopy were used
      to confirm the formed product and showed that three phytanate anions are
      complexed with one lanthanide cation. The physicochemical properties of the
      lanthanide phytanates were investigated using DSC, XRD, SAXS, and cross-polarized
      optical microscopy. Several of the hydrated salts form a liquid-crystalline
      hexagonal columnar mesophase at room temperature, and samarium(III) phytanate
      forms this phase even in the absence of water. Select lanthanide phytanates were
      dispersed in water, and cryo-TEM images indicate that some structure has been
      retained in the dispersed phase. NMR relaxivity measurements were conducted on
      these systems. It has been shown that a particulate dispersion of gadolinium(III)
      phytanate displays proton relaxivity values comparable to those of a commercial
      contrast agent for magnetic resonance imaging and a colloidal dispersion of
      europium(III) phytanate exhibits the characteristics of a fluorescence imaging
      agent.

PMID- 20039653
TI  - Single chain diffusion of poly(ethylene oxide) in its monolayers before and after
      crystallization.
AB  - Lateral diffusion of single chain related to the crystallization process of
      poly(ethylene oxide) (PEO) in its monolayers on silica surfaces is studied by
      single molecule fluorescence microscopy and single molecule tracking techniques.
      Diffusion of PEO chains is observed in the supercooled state before
      crystallization as well as in the noncrystalline regions after crystallization.
      In the postcrystallization monolayers, the diffusion coefficient of PEO chains is
      an order of magnitude lower than that in the supercooled state before
      crystallization. The origin is attributed to the change of polymer surface
      concentration due to the consumption of polymer molecules in the crystal
      formation. This is supported by the results showing a monotonous decrease of
      diffusion coefficient with the thickness decrease of the monolayer in its
      supercooled state. The PEO chains take a more flattened conformation under lower
      surface concentration and stick stronger to the surface. As a consequence, the
      diffusion rate is reduced. The results clearly demonstrate a strong mutual effect
      between the crystallization process and the mass transportation for the polymer
      crystallization under surface confinement.

PMID- 20039654
TI  - Facile formation of branched titanate nanotubes to grow a three-dimensional
      nanotubular network directly on a solid substrate.
AB  - The hydrothermal formation of branched titanate nanotubes that grow a 3D
      nanotubular network directly onto a titanium substrate is reported. The resultant
      3D nanotubular network exhibits a unique all-dimensional uniform porous
      structure. The inner and outer tubular diameters of branched titanate nanotubes
      were found to be approximately 6 and 12 nm, respectively. For the majority of the
      nanotubes, the wall is formed from three layers of titanate with an approximate
      7.7 A interlayer space. In terms of individual nanotubes, these characteristics
      are quantitatively similar to those of previously reported nonbranched nanotubes.
      However, in terms of how nanotubes are arranged in the film, the all-dimensional
      uniform nanotubular network structure obtained here is distinctively different
      from those of previously reported structures. The 3D nanotubular network
      structure was formed by the jointing of branched nanotubes. In contrast, the
      previously reported nanotubes tend to grow vertically on the substrate, and the
      resultant tubular films are formed by interwoven nonbranched nanotubes. The
      branched titanate nanotubes can be readily formed on titanium substrates but not
      in solution suspension forms. A continuous seed formation-oriented crystal growth
      mechanism was proposed for the branched titanate nanotubular network formation.
      Such a network structure could be useful for applications such as photocatalysis,
      membrane separation, field emission, and photovoltaic devices.

PMID- 20039655
TI  - Morphological control of the electrochemically deposited poly(4
      vinyltriphenylamines) (PVTPAs).
AB  - The morphology of the thin films obtained from electrochemical deposition of
      poly(4-vinyltriphenylamine)s (PVTPAs) on ITO surface varies as their molecular
      weight increases. The SEM studies revealed that while uniform coating could be
      obtained from low molecular weight PVTPAs (approximately 2700), uneven and rough
      coating with numerous cracks on the surface would be formed from high molecular
      weight PVTPAs. These defects could be reduced by using our surface modification
      strategy, in which the ITO surface was first primed with a thin layer of
      electrochemical coating of poly(methylenetriphenylamine) (PMTPA). This coating
      would turn the highly polar ITO surface into a nonpolar conducting surface that
      benefits for the PVTPA deposition. Our electroluminescence test suggested that
      this type of PMTPA/PVTPA composite film is good for hole injection and
      transportation.

PMID- 20039656
TI  - Polarization of nanorods submerged in an electrolyte solution and subjected to an
      ac electrical field.
AB  - Recently, there has been growing interest in utilizing electrical fields to
      position and separate rod-shaped particles such as DNA molecules, actin
      filaments, microtubules, viruses, bacteria, nanotubes, and nanorods. The
      polarization of the electrical double layer, enveloping the rod, plays a critical
      role in determining the magnitude and direction of the rod's dipole moment. We
      consider noninteracting, rod-shaped (spherocylinder) particles and calculate the
      induced dipole moment as a function of the electrical field frequency, the rod's
      aspect ratio (length/radius), the rod's free surface charge, and the double-layer
      thickness. To this end, we solve the Poisson-Nernst-Planck (PNP) equations for
      the ions' migration, diffusion, and convection. When the surface charge is small
      and the rod is short, the dipole moment is negative. As the rod's length
      increases, the dipole moment increases and eventually changes sign from negative
      to positive. The dipole coefficient of a rod, whose length is greater than some
      critical value, increases linearly with length. This latter observation
      simplifies the estimation of the dipole moment of particles with large aspect
      ratios (length/radius). The theoretical predictions are compared and favorably
      agree with experimental data for double-stranded, short DNA molecules.

PMID- 20039657
TI  - Microfluidic fabrication of stable nanoparticle-shelled bubbles.
AB  - We introduce a microfluidic approach to generating monodisperse, stable
      nanoparticle-shelled bubbles using air-in-oil-in-water (A/O/W) compound bubbles
      as templates. The oil phase of the A/O/W compound bubbles comprises a volatile
      organic solvent and a hydrophobic silica nanoparticle. Upon evaporation of the
      organic solvent, the nanoparticles in the oil layer form a stiff shell at the air
      water interface, which drastically enhances the stability of the bubbles against
      dissolution and coarsening. On the basis of this approach, we demonstrate that it
      is also possible to generate functional bubbles stabilized by composite shells
      that are composed of mixtures of hydrophobic materials and nanoparticles with
      unique properties.

PMID- 20039658
TI  - Extreme sensitivity of circular dichroism to long-range excitonic couplings in
      helical supramolecular assemblies.
AB  - Circular dichroism (CD) spectroscopy is an ideal tool for studying the self
      assembly of helical supramolecular assemblies since it is very sensitive to
      extended excitonic couplings between chiral chromophores. We show that the CD
      spectrum retains its high sensitivity to long-range interactions even in the
      presence of extreme disorder and strong interaction with vibrations when
      excitations are mainly localized on individual molecules. We derive a universal
      expression for the first moment of the CD spectrum of helical assemblies in terms
      of a modulated sum over excitonic couplings, which is independent of the strength
      of the energetic disorder, the spatial correlation of the disorder, and the
      strength of the interaction with vibrations. This demonstrates that excitonic
      couplings can be directly extracted from experimental CD spectra without having
      information about the energetic disorder and vibrational interactions. We apply
      our results to helical assemblies of functionalized chiral oligo(p
      phenylenevinylene) molecules and show that existing theoretical values for the
      excitonic couplings should be adapted in order to obtain agreement with the
      experimental CD spectrum.

PMID- 20039659
TI  - Computational studies on response and binding selectivity of fluorescence
      sensors.
AB  - Using a computational strategy based on density functional theory calculations,
      we successfully designed a fluorescent sensor for detecting Zn(2+) [J. Phys.
      Chem. B 2006, 110, 22991-22994]. In this work, we report our further studies on
      the computational design protocol for developing Photoinduced Electron Transfer
      (PET) fluorescence sensors. This protocol was applied to design a PET
      fluorescence sensor for Zn(2+) ions, which consists of anthracene as the
      fluorophore connected to pyridine as the receptor through dimethylethanamine as
      the linker. B3LYP and time-dependent B3LYP calculations were performed with the
      basis set 6-31G(d,p), 6-31+G(d,p), 6-311G(d,p), and 6-311+G(d,p). The calculated
      HOMO and LUMO energies of the fluorophore and receptor using all four basis sets
      show that the relative energy levels remain unchanged. This indicates that any of
      these basis sets can be used in calculating the relative molecular orbital (MO)
      energy levels. Furthermore, the relative MO energies of the independent
      fluorophore and receptor are not altered when they are linked together, which
      suggests that one can calculate the MO energies of these components separately
      and use them as the MO energies of the free sensor. These are promising outcomes
      for the computational design of sensors, though more case studies are needed to
      further confirm these conclusions. The binding selectivity studies indicate that
      the predicted sensor can be used for Zn(2+) even in the presence of the divalent
      cation, Ca(2+).

PMID- 20039660
TI  - Optimization of parameters used in algorithms of ion-mobility calculation for
      conformational analyses.
AB  - Structural information of gaseous ions can be obtained by comparing their
      collision cross sections as determined by ion-mobility experiments with those by
      theoretical modeling. Three theoretical models, the projection approximation
      (PA), the exact hard-sphere scattering (EHSS), and the trajectory (TJ) models,
      have been employed to determine the theoretical cross sections of candidate
      geometries. The accuracy of these models is largely dependent on the empirical
      parameters used for ion-buffer gas interactions. Optimal empirical parameters for
      each model have been determined by comparing the experimental cross sections of
      20 calibrant ions with their theoretical cross sections obtained by using
      geometries sampled by density-functional-theory-based molecular dynamics
      simulations. The maximum absolute deviations of the cross sections of 15.5% (PA),
      20.7% (EHSS), and 11.7% (TJ) obtained from the original parameters are reduced to
      5.6% (PA), 4.6% (EHSS), and 3.4% (TJ) obtained from the new optimized parameters.
      The root-mean-square deviations of the predicted cross sections using the new
      parameters from the experimental values are also drastically reduced to 2.1%
      (PA), 1.9% (EHSS), and 1.6% (TJ). The new parameters are verified on protonated
      triglycine, protonated trialanine, and doubly protonated bradykinin.

PMID- 20039661
TI  - Nanostructure-dependent water-droplet adhesiveness change in superhydrophobic
      anodic aluminum oxide surfaces: from highly adhesive to self-cleanable.
AB  - Water-droplet adhesiveness was freely controlled on a single platform of
      superhydrophobic anodized aluminum oxide (AAO) within the range from highly
      adhesive to self-cleanable. Changing the structure from nanopore to nanopillar
      arrays at the surface caused a dramatic increase in the receding angle and a
      decrease in the hysteresis of water contact angles. The presence of dead-end
      nanopores but not through nanoholes was recognized as one of the main causes of
      the adhesiveness of superhydrophobic surfaces. The adhesiveness-controllable
      superhydrophobic AAO can be an excellent platform on which to elucidate the
      physical nature of the wetting phenomenon related to the nanostructure and has
      promising potential in technological applications.

PMID- 20039662
TI  - Estrogen receptor interactions and dynamics monitored in live cells by
      fluorescence cross-correlation spectroscopy.
AB  - Quantitative characterization of protein interactions in live cells remains one
      of the most important challenges in modern biology. In the present work we have
      used two-photon, two-color, fluorescence cross-correlation spectroscopy (FCCS) in
      transiently transfected COS-7 cells to measure the concentrations and
      interactions of estrogen receptor (ER) subtypes alpha and beta with one of their
      transcriptional coactivator proteins, TIF2, as well as heterodimerization between
      the two ER subtypes. Using this approach in a systematic fashion, we observed a
      strong ligand-dependent modulation of receptor-coactivator complexation, as well
      as strong protein concentration dependence for complex formation in the absence
      of ligand. These quantitative values for protein and complex concentrations
      provide the first estimates for the ER-TIF2 K(d) for the full-length proteins and
      in a cellular context (agonist, < approximately 6 nM; antagonist, > approximately
      3 microM; unliganded, approximately 200 nM). Coexpression of the two ER subtypes
      revealed substantial receptor heterodimer formation. They also provide, for the
      first time, estimated homo- and heterodimerization constants found to be similar
      and in the low nanomolar range. These results underscore the importance of
      receptor and coregulator expression levels and stability in the tissue-dependent
      modulation of receptor function under normal and pathological conditions.

PMID- 20039663
TI  - Effects of the RGTFEGKF inhibitor on the structures of the transmembrane fragment
      70-86 of glycophorin A: an all-atom molecular dynamics study.
AB  - There is experimental evidence that the transmembrane fragment spanning amino
      acids 70-86 of glycophorin A, GpA70-86, forms amyloid fibrils and the inhibitor
      RGTFEGKF prevents GpA70-86 fibril formation at an equimolar ratio. Both the GpA70
      86 and inhibitor peptides contain a GxxxG motif as found in many amyloid proteins
      such as the Alzheimer's amyloid beta-peptide and prion protein. To explore the
      intrinsic, early interaction and inhibition mechanism, we have determined the
      structures of GpA70-86 in the absence and presence of the inhibitor by means of
      extensive molecular dynamics simulations in explicit solvent. Consistent with
      experiments on the fibrils, our simulations show that the two GxxxG motifs
      interact significantly at the monomer level. They go, however, one step beyond by
      indicating that the inhibitor has a significant impact on the global structure of
      GpA70-86, but a limited influence on the conformations of the GxxxG motif.
      Implications of our simulations on amyloid propagation of proteins containing
      GxxxG motifs are discussed.

PMID- 20039664
TI  - Aqueous solvation of p-aminobenzonitrile in the excited states: a molecular level
      theory on density dependence.
AB  - Osawa et al. recently studied density dependence of electronic absorption spectra
      of p-aminobenzonitrile (ABN) in supercritical and subcritical water. They
      reported the peak position exhibits a minimum in a specific density. RISM-SCF
      SEDD, which is a combination method of ab initio electronic structure theory and
      a statistical mechanics for molecular liquids, was applied to address the origin
      of this challenging phenomena. Highly accurate electronic structure theories
      (CASSCF and MCQDPT2) coupled with microscopic description of hydrogen bonding
      were employed over a wide range of density condition. We found that the solvation
      effects on the lower two excited states show different density dependence,
      suggesting that the turnover is attributed to the difference in sensitivity to
      solvent of the two states.

PMID- 20039665
TI  - Aggregation properties of the peptide fragments derived from the 17-29 region of
      the human and rat IAPP: a comparative study with two PEG-conjugated variants of
      the human sequence.
AB  - The amyloidogenic amino acid sequence Ac-VHSSNNFGAILSS-NH(2), corresponding to
      the 17-29 peptide region of human amylin (hIAPP17-29), was modified by grafting a
      hydrophilic PEG chain in order to obtain a novel class of peptides to be used as
      models to study the aggregation process of the full-length IAPP. The amphiphilic
      feature of the pegylated peptide fragment at the N-terminus (PEG-N-hIAPP17-29)
      drives the aggregation process toward stable micellar clusters without
      fibrillogenesis, despite the presence of beta-sheet interaction between peptides
      at pH values higher than 4.0. The hIAPP17-29-C-PEG, in which the PEG moiety is
      linked to the C-terminus, does not possess analogous amphiphilic character and
      the ability of PEG in forming H-bonds with the solvent overcomes that of the
      peptide chain, thereby causing peptide flocculation. The comparison with the
      unmodified hIAPP17-29 and the rat's peptide sequence Ac-VRSSNNLGPGLPP
      NH(2)(rIAPP17-29) revealed the crucial role of hydrogen bonding between peptide
      and solvent in determining the aggregate structure and preventing fibril
      formation, as well as the non-negligible effect of a small amount of organic
      solvent in the aqueous solution which affects the aggregation process and rate.

PMID- 20039666
TI  - Influence of the solvent on the self-assembly of a modified amyloid beta peptide
      fragment. II. NMR and computer simulation investigation.
AB  - The conformation of a model peptide AAKLVFF based on a fragment of the amyloid
      beta peptide Abeta16-20, KLVFF, is investigated in methanol and water via
      solution NMR experiments and molecular dynamics computer simulations. In previous
      work, we have shown that AAKLVFF forms peptide nanotubes in methanol and twisted
      fibrils in water. Chemical shift measurements were used to investigate the
      solubility of the peptide as a function of concentration in methanol and water.
      This enabled the determination of critical aggregation concentrations. The
      solubility was lower in water. In dilute solution, diffusion coefficients
      revealed the presence of intermediate aggregates in concentrated solution,
      coexisting with NMR-silent larger aggregates, presumed to be beta-sheets. In
      water, diffusion coefficients did not change appreciably with concentration,
      indicating the presence mainly of monomers, coexisting with larger aggregates in
      more concentrated solution. Concentration-dependent chemical shift measurements
      indicated a folded conformation for the monomers/intermediate aggregates in
      dilute methanol, with unfolding at higher concentration. In water, an
      antiparallel arrangement of strands was indicated by certain ROESY peak
      correlations. The temperature-dependent solubility of AAKLVFF in methanol was
      well described by a van't Hoff analysis, providing a solubilization enthalpy and
      entropy. This pointed to the importance of solvophobic interactions in the self
      assembly process. Molecular dynamics simulations constrained by NOE values from
      NMR suggested disordered reverse turn structures for the monomer, with an
      antiparallel twisted conformation for dimers. To model the beta-sheet structures
      formed at higher concentration, possible model arrangements of strands into beta
      sheets with parallel and antiparallel configurations and different stacking
      sequences were used as the basis for MD simulations; two particular arrangements
      of antiparallel beta-sheets were found to be stable, one being linear and twisted
      and the other twisted in two directions. These structures were used to simulate
      circular dichroism spectra. The roles of aromatic stacking interactions and
      charge transfer effects were also examined. Simulated spectra were found to be
      similar to those observed experimentally (in water or methanol) which show a
      maximum at 215 or 218 nm due to pi-pi* interactions, when allowance is made for a
      15-18 nm red-shift that may be due to light scattering effects.

PMID- 20039667
TI  - Functional cycloamylose as a polysaccharide-based biomaterial: application in a
      gene delivery system.
AB  - Cycloamylose (CA) exhibits differences in geometry and greater colloidal
      stability compared with amylose. Here we report the synthesis of a cationic CA
      derivative and its application for gene delivery. Cationic CA (catCA) and
      cationic amylose (catAmy) were synthesized by introducing spermine groups. The
      interactions between catCA or catAmy with plasmid DNA encoding firefly luciferase
      was examined by gel electrophoresis, dynamic light scattering, and transmission
      electron microscopy. Activity as a gene delivery system was evaluated by flow
      cytometry and luciferase assays. CatCA formed a condensed pDNA complex (
      approximately 250 nm in size). The catCA complex showed enhanced cellular uptake
      and greater transfection efficiency than the catAmy complex. Hemolysis by
      membrane destabilization and the effects of hydroxychloroquine on transfection
      ability suggest that the formation of a supramolecular complex with CA is
      important for high transfection activity. These results suggested that CA can be
      used as new polysaccharide-based biomaterials.

PMID- 20039668
TI  - Effect of mycorrhizal fungi on the phytoremediation of hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX).
AB  - The objective of this research was to decrease the bioaccumulation of RDX
      (hexahydro-1,3,5-trinitro-1,3,5-triazine) in the leaves of switchgrass (Panicum
      virgatum) and hybrid poplar trees (Populus deltoides x nigra, DN34) by exploiting
      the symbiotic relationship between these plants and mycorrhizal fungi. Prior to
      dosing with uniformly labeled (14)C-RDX, plants were grown for three months to
      establish the symbiosis. Results showed that the presence of mycorrhizal fungi
      does not significantly decrease the concentration of RDX in leaf tissues for
      experimental periods of 30 days. Results also indicated that a radiolabeled
      volatile organic compound was emitted by both plant species. This is the first
      evidence that a whole plant can facilitate the transformation of RDX to a
      volatile organic chemical.

PMID- 20039669
TI  - Influence of size on the rate of mesoporous electrodes for lithium batteries.
AB  - High power rechargeable lithium batteries are a key target for transport and load
      leveling, in order to mitigate CO(2) emissions. It has already been demonstrated
      that mesoporous lithium intercalation compounds (composed of particles containing
      nanometer diameter pores separated by walls of similar size) can deliver high
      rate (power) and high stability on cycling. Here we investigate how the critical
      dimensions of pore size and wall thickness control the rate of intercalation
      (electrode reaction). By using mesoporous beta-MnO(2), the influence of these
      mesodimensions on lithium intercalation via single and two-phase intercalation
      processes has been studied in the same material enabling direct comparison. Pore
      size and wall thickness both influence the rate of single and two-phase
      intercalation mechanisms, but the latter is more sensitive than the former.

PMID- 20039670
TI  - Unexpected CO2 splitting reactions to form CO with N-heterocyclic carbenes as
      organocatalysts and aromatic aldehydes as oxygen acceptors.
AB  - The catalytic reduction of carbon dioxide to carbon monoxide under mild
      conditions using aromatic aldehydes as reductants and NHCs as organocatalysts was
      developed. This carbon dioxide splitting reaction provides a new method for metal
      free carbon dioxide reduction and steps forward in utilizing carbon dioxide as a
      renewable "green" source under mild conditions. On the other hand, this reaction
      also shows a new economical way to oxidize aromatic aldehydes under mild
      conditions with carbon dioxide and could be applied in pharmaceutical synthesis.

PMID- 20039671
TI  - Control over catenation in metal-organic frameworks via rational design of the
      organic building block.
AB  - Metal-organic frameworks (MOFs), a hybrid class of materials comprising inorganic
      nodes and organic struts, have potential application in many areas due to their
      high surface areas and uniform pores and channels. One of the key challenges to
      be overcome in MOF synthesis is the strong propensity for catenation (growth of
      multiple independent networks within a given crystal), as catenation reduces
      cavity sizes and diminishes porosity. Here we demonstrate that rational design of
      organic building blocks, which act as strut-impervious scaffolds, can be
      exploited to generate highly desired noncatenated materials in a controlled
      fashion.

PMID- 20039672
TI  - The HN(COCA)HAHB NMR experiment for the stereospecific assignment of Hbeta
      protons in non-native states of proteins.
AB  - (3)J(H(alpha),H(beta))-coupling constants deliver precious information on the
      population of the three favored chi(1)-rotamers in unfolded states of proteins.
      Here, a novel pulse sequence, tailored toward the NMR analysis of non-native
      states of proteins, the HN(COCA)HAHB experiment, is developed to measure
      (3)J(H(alpha),H(beta)). In four subsequent INEPT steps, magnetization is
      transferred from H(N) to H(alpha). In a COSY-like magnetization transfer step,
      dephasing of magnetization on H(alpha) is quantified to determine the
      (3)J(H(alpha),H(beta))-coupling constants. Analysis of the measured homonuclear
      coupling constants, together with measurement of heteronuclear (3)J(N,C(gamma))-
      and (3)J(C',C(gamma))-coupling constants, allows stereospecific assignment of the
      two diastereotopic H(beta)-protons even in unfolded states of proteins, and the
      derivation of populations according to a Pachler-type analysis.

PMID- 20039673
TI  - Addition of amines and hydroborane to the disilyne RSi[triple bond]SiR (R =
      Si(i)Pr[CH(SiMe3)2]2) giving amino- and boryl-substituted disilenes.
AB  - The reaction of 1,1,4,4-tetrakis[bis(trimethylsilyl)methyl]-1,4
      diisopropyltetrasila-2-yne 1 with diethylamine or diphenylamine produced the
      corresponding amino-substituted disilenes R(R'(2)N)Si=SiHR 2a, b (R =
      Si(i)Pr[CH(SiMe(3))(2)](2), R' = Et (2a), Ph (2b)). The reaction of 1 with 9
      borabicyclo[3.3.1]nonane afforded the boryl-substituted disilene
      R(R''(2)B)Si=SiHR 3 (R''(2)B = 9-borabicyclo[3.3.1]nonan-9-yl). Spectroscopic and
      X-ray crystallographic analyses of 2a, b, and 3 showed that 2a and 3 have a
      coplanar arrangement of the Si=Si double bond and amino or boryl groups, giving
      pi-conjugation between the Si=Si double bond and the lone pair on the nitrogen
      atom or vacant 2p orbital on the boron atom, whereas 2b exhibits no such
      conjugation.

PMID- 20039674
TI  - Single domain antibodies are specially suited for quantitative determination of
      gliadins under denaturing conditions.
AB  - Food intended for celiac patients' consumption must be analyzed for the presence
      of toxic prolamins using high detectability tests. Though 60% ethanol is the most
      commonly used solvent for prolamins extraction, 2-mercaptoethanol (2-ME) and
      guanidinium chloride (GuHCl) can be added to increase protein recovery. However,
      ethanol and denaturing agents interfere with antigen recognition when
      conventional antibodies are used. In the present work, a new method for gliadins
      quantification is shown. The method is based on the selection of llama single
      domain antibody fragments able to operate under denaturing conditions. Six out of
      28 VHH-phages obtained retained their binding capacity in 15% ethanol. Selected
      clones presented a long CDR3 region containing two additional cysteines that
      could be responsible for the higher stability. One of the clones (named VHH26)
      was fully operative in the presence of 15% ethanol, 0.5% 2-ME, and 0.5 M GuHCl.
      Capture ELISA using VHH26 was able to detect gliadins in samples shown as
      negatives by conventional ELISA. Therefore, this new strategy appears as an
      excellent platform for quantitative determination of proteins or any other
      immunogenic compound, in the presence of denaturing agents, when specific
      recognition units with high stability are required.

PMID- 20039675
TI  - The influence of stereochemistry of antioxidants and flavonols on oxidation
      processes in a model wine system: ascorbic acid, erythorbic acid, +-catechin and
      (-)-epicatechin.
AB  - The stereochemical influence of antioxidant and flavanol compounds on oxidation
      processes in a model wine system was studied. The diastereoisomers, ascorbic acid
      and erythorbic acid, were used as antioxidants in a model wine system containing
      either (+)-catechin or (-)-epicatechin as the oxidizable flavanol compound.
      Samples were stored at 45 degrees C for a period of 14 days and analyzed by
      UV/visible spectrometry, CIELab, UPLC-PDA, and LC-MS. The results showed that
      less brown oxidative coloration occurred for samples with erythorbic acid for a
      given flavanol compound, while (+)-catechin provided less yellow coloration for a
      given antioxidant. Although erythorbic acid was degraded faster than ascorbic
      acid, it was associated with less decay in the accompanying flavanol compound.
      Xanthylium cation pigments were identified as the major contributor to color
      development. Furthermore, the production of pigment precursors, previously
      identified as furanone-substituted flavanols, was confirmed in all cases and
      their corresponding xanthylium cation pigments were lower in the presence of
      erythorbic acid than ascorbic acid. The results demonstrate that erythorbic acid
      is more efficient at minimizing oxidative color development than ascorbic acid in
      the model wine system.

PMID- 20039676
TI  - Di-D-fructose dianhydride-enriched products by acid ion-exchange resin-promoted
      caramelization of D-fructose: chemical analyses.
AB  - Caramelization commonly occurs when sugars, or products containing a high
      proportion of sugars, are heated either dry or in concentrated aqueous solutions,
      alone or in the presence of certain additives. Upon thermal treatment of sugars,
      dehydration and self-condensation reactions occur, giving rise to volatiles
      (principally 2-hydroxymethylfurfural, HMF), pigments (melanoidines) and
      oligosaccharidic material, among which di-D-fructose dianhydrides (DFAs) and
      glycosylated DFA derivatives of different degree of polymerization (DP) have been
      identified. This study reports a methodology to produce caramel-like products
      with a high content of DFAs and oligosaccharides thereof from commercial D
      fructose based on the use of acid ion-exchange resins as caramelization
      promotors. The rate of formation of these compounds as a function of D-fructose
      concentration, catalyst proportion, temperature, catalyst nature and particle
      size has been investigated. The use of sulfonic acid resins allows conducting
      caramelization at remarkable low temperatures (70-90 degrees C) to reach
      conversions into DFA derivatives up to 70-80% in 1-2 h, with relative proportions
      of HMF < 2%.The relative abundance of individual DFA structures can be modulated
      by acting on the catalyst nature and reaction conditions, which offers a unique
      opportunity for nutritional studies of DFA-enriched products with well-defined
      compositions.

PMID- 20039677
TI  - In vitro hepatic biotransformation of aspalathin and nothofagin, dihydrochalcones
      of rooibos (Aspalathus linearis), and assessment of metabolite antioxidant
      activity.
AB  - Aspalathin (2',3,4,4',6'-pentahydroxy-3'-C-beta-d-glucopyranosyldihydrochalcone)
      is the major flavonoid present in the South African herbal tea rooibos. In vitro
      metabolism of aspalathin and a structural analogue nothofagin, lacking the A ring
      catechol group, was investigated by monitoring the formation of glucuronyl and
      sulfate conjugates using Aroclor 1254 induced and uninduced rat liver microsomal
      and cytosolic subcellular fractions. Following glucuronidation of both aspalathin
      and nothofagin, HPLC-DAD, LC-MS, and LC-MS/MS analyses indicated the presence of
      two metabolites: one major and one minor. Only one aspalathin metabolite was
      obtained after sulfation, while no metabolites were observed for nothofagin. Two
      likely sites of conjugation for aspalathin are 4-OH or 3-OH on the A-ring. For
      nothofagin, the 4-OH (A-ring) and 6'-OH (B-ring) seem to be involved. The
      glucuronyl conjugates of aspalathin lack any radical scavenging properties in
      online postcolumn DPPH radical and ABTS radical cation assays. Deconjugation
      assays utilizing glucuronidase and sulfatase resulted in the disappearance of the
      metabolites, with the concomitant formation of the unconjugated form in the case
      of the glucuronidated product. The balance between conjugated and unconjugated
      forms of aspalathin could have important implications regarding its role in
      affecting oxidative status in intra- and extracellular environments in vivo.

PMID- 20039678
TI  - Functionality of short chain amylose-lipid complexes in starch-water systems and
      their impact on in vitro starch degradation.
AB  - Monodisperse short-chain amorphous or semicrystalline amylose-glycerol
      monostearate (GMS) complexes, or, as a reference, pure GMS, were added to starch
      dispersions which were gelatinized and allowed to cool. The largest impacts on
      rheological properties were observed when GMS or amorphous GMS complexes were
      added. The controlled release of the short amylose chains of the latter induced
      double helix and, thus, network formation, resulting in higher viscosity
      readings. As the lipid is set free after starch gelatinization, it is assumed
      that it complexes with amylose leached outside the granule, whereas additional
      pure GMS can probably to a greater extent complex inside the granule.
      Semicrystalline complexes could be considered as inert mass in the starch systems
      as their melting temperature exceeded the temperature reached during the
      experiment. The additives also impacted starch's sensitivity to enzymatic
      degradation. GMS addition reduced the resistant starch (RS) content of the gels
      and increased their hydrolysis index (HI). Added amorphous or semicrystalline
      complexes, on the other hand, yielded gels with a higher RS content and a lower
      HI. Addition of amylose-lipid complexes to starch suspensions impacts starch gel
      characteristics and decreases its digestion rate, possibly by releasing short
      amylose chains in a controlled way that then participate in amylose
      crystallization and, hence, RS formation.

PMID- 20039679
TI  - Comparison of electron spin resonance spectroscopy and inductively-coupled plasma
      optical emission spectroscopy for biodistribution analysis of iron-oxide
      nanoparticles.
AB  - Magnetic nanoparticles (MNP) have been widely studied for use in targeted drug
      delivery. Analysis of MNP biodistribution is essential to evaluating the success
      of targeting strategies and the potential for off-target toxicity. This work
      compared the applicability of inductively coupled plasma optical emission
      spectroscopy (ICP-OES) and electron spin resonance (ESR) spectroscopy in
      assessing MNP biodistribution. Biodistribution was evaluated in 9L-glioma bearing
      rats administered with MNP (12-25 mg Fe/kg) under magnetic targeting. Ex vivo
      analysis of MNP in animal tissues was performed with both ICP-OES and ESR. A
      cryogenic method was developed to overcome the technical hurdle of loading tissue
      samples into ESR tubes. Comparison of results from the ICP-OES and ESR
      measurements revealed two distinct relationships for organs accumulating high or
      low levels of MNP. In organs with high MNP accumulation such as the liver and
      spleen, data were strongly correlated (r = 0.97, 0.94 for the liver and spleen,
      respectively), thus validating the equivalency of the two methods in this high
      concentration range (>1000 nmol Fe/g tissue). The two sets of measurements,
      however, differed significantly in organs with lower levels of MNP accumulation
      such as the brain, kidney, and the tumor. Whereas ESR resolved MNP to 10-55 nmol
      Fe/g tissue, ICP-OES failed to detect MNP because of masking by endogenous iron.
      These findings suggest that ESR coupled to cryogenic sample handling is more
      robust than ICP-OES, attaining better sensitivity in analyses. Such advantages
      render ESR the method of choice for accurate profiling of MNP biodistribution
      across tissues with high variability in nanoparticle accumulation.

PMID- 20039680
TI  - Propylammonium nitrate as a solvent for amphiphile self-assembly into micelles,
      lyotropic liquid crystals, and microemulsions.
AB  - The phase behavior and self-assembled microstructures of a range of
      oligo(oxyethylene)-n-alkyl ether (C(i)E(j)) surfactants has been investigated in
      propylammonium nitrate (PAN), a room temperature ionic liquid. Micelles and
      single-phase microemulsions were all found to form at alkyl chain lengths from
      dodecyl to octadecyl, and lyotropic liquid crystals formed with hexadecyl chains
      or longer. Small-angle neutron scattering (SANS) shows that self-assembly occurs
      by solvophobic interactions driving the aggregation of the alkyl chains, but
      several results indicate that these are weaker in PAN than in water or
      ethylammonium nitrate, due chiefly to the hydrophobicity of PAN. Longer alkyl
      chains are needed for lyotropic liquid crystals to form, and higher surfactant
      concentrations are needed to form a single phase microemulsion. Conductivity
      shows these microemulsions to be weakly structured, and relatively insensitive to
      oil or surfactant molecular structure, unlike water-based systems. However, SANS
      contrast variation reveals a nanosegregation of oil from the alkyl tails of
      surfactants within the microemulsion, and may suggest a cosurfactant-like role
      for the propylammonium cation. Molecular areas within microemulsions and lamellar
      phases are larger than corresponding water- or ethylammonium nitrate-based
      systems due to the large molecular volume of the solvating PANs.

PMID- 20039681
TI  - Deconvolution of mixture spectra from ion-trap data-independent-acquisition
      tandem mass spectrometry.
AB  - Data-independent tandem mass spectrometry isolates and fragments all of the
      molecular species within a given mass-to-charge window, regardless of whether a
      precursor ion was detected within the window. For shotgun proteomics on complex
      protein mixtures, data-independent MS/MS offers certain advantages over the
      traditional data-dependent MS/MS: identification of low-abundance peptides with
      insignificant precursor peaks, more direct relative quantification, free of
      biases caused by competing precursors and dynamic exclusion, and faster
      throughput due to simultaneous fragmentation of multiple peptides. However, data
      independent MS/MS, especially on low-resolution ion-trap instruments, strains
      standard peptide identification programs, because of less precise knowledge of
      the peptide precursor mass and large numbers of spectra composed of two or more
      peptides. Here we describe a computer program called DeMux that deconvolves
      mixture spectra and improves the peptide identification rate by approximately
      25%. We compare the number of identifications made by data-independent and data
      dependent MS/MS at the peptide and protein levels: conventional data-dependent
      MS/MS makes a greater number of identifications but is less reproducible from run
      to run.

PMID- 20039682
TI  - Determination of Fab-hinge disulfide connectivity in structural isoforms of a
      recombinant human immunoglobulin G2 antibody.
AB  - The detection and characterization of unexpected disulfide-mediated structural
      variants of human immunoglobulin G2 (IgG2) antibodies was recently the subject of
      two copublications. In this paper, we present data to confirm the previously
      reported structures and elucidate the complete disulfide connectivity of each
      variant through the application of a novel analytical methodology. In this
      manner, the data illustrate the presence of at least five structural variants,
      including the classical structure with independent Fab domains and a hinge
      region. Multiple subvariants of the IgG2-A/B and IgG2-B structures are
      identified; these subvariants of each structure differ through the order of
      attachment of Fab peptides to the sequential hinge cysteines. Furthermore, the
      connectivity of a novel subvariant of IgG2-B containing an intrachain disulfide
      linkage in the lower hinge region is elucidated. The results presented in this
      paper reveal that the population of IgG2 disulfide structural variants is yet
      more complex than recently reported.

PMID- 20039683
TI  - New glucosidase inhibitors from an ayurvedic herbal treatment for type 2
      diabetes: structures and inhibition of human intestinal maltase-glucoamylase with
      compounds from Salacia reticulata.
AB  - An approach to controlling blood glucose levels in individuals with type 2
      diabetes is to target alpha-amylases and intestinal glucosidases using alpha
      glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases
      targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one
      of the four intestinal glycoside hydrolase 31 enzyme activities responsible for
      the hydrolysis of terminal starch products into glucose. Here we present the X
      ray crystallographic studies of ntMGAM in complex with a new class of alpha
      glucosidase inhibitors derived from natural extracts of Salacia reticulata, a
      plant used traditionally in Ayuverdic medicine for the treatment of type 2
      diabetes. Included in these extracts are the active compounds salacinol,
      kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated
      kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03
      microM), some 2000-fold better than the compounds currently used in the clinic,
      and highlights the potential of the salacinol class of inhibitors as future drug
      candidates.

PMID- 20039684
TI  - Molecular dynamics study of the melt morphology of polyethylene chains with
      different branching characteristics adjacent to a clay surface.
AB  - Conformations of model high-density polyethylene (HDPE) and linear low-density
      polyethylene (LLDPE) chains with different intramolecular branch distributions
      adsorbed on a relaxed octahedral surface of kaolinite, a major clay mineral, at
      463 K (190 degrees C) were studied by using classical molecular dynamics (MD)
      simulation. Prior to the MD simulations, first-principle density functional
      theory (DFT) calculations were carried out to relax the inorganic surface that
      was created by cleaving the corresponding kaolinite crystal structure. The high
      temperature MD simulation results showed that an ordered polyethylene region with
      a thickness of about one to three layers of chain segments developed rapidly near
      the clay surface. On the other hand, chain segments in the far field slowly
      evolved into another ordered region with a higher degree of order than the one
      adjacent to the surface. It was observed that the melt morphology in the far
      field depends on the architecture of the chains. Also, in between the two ordered
      regions, a region that contained no apparent order formed. The above observation
      is attributed to the fact that the mobility of chain segments adjacent to the
      surface was greatly reduced as a result of their strong affinity for the surface,
      while those in the far field were not. Despite the fact that the results are for
      the melt state, they suggest that nucleation and lamellar growth of polymer
      chains nearby an inorganic surface may proceed from the chain segments in the
      ordered region in the far field rather than from the organic/inorganic interface.
      This is because chain segments in the three described regions, upon cooling,
      should not have sufficient thermal energy to reorient themselves drastically to
      form a single lamella under normal crystallization conditions. However, it should
      be noted that the above speculation is made based on a rather short equilibration
      time (approximately 10 ns) used in the simulations.

PMID- 20039685
TI  - Thin nanocomposite films of polyaniline/Au nanoparticles by the Langmuir-Blodgett
      technique.
AB  - The Langmuir-Blodgett (LB) method was used to deposit multilayers of polyaniline
      (PANI)- and mercaptoethanesulfonate (MES)-stabilized Au nanoparticles. The
      electrostatic interaction between the negatively charged nanoparticles in the
      subphase and the positively charged PANI at the air-water interface assisted the
      deposition of the nanocomposite film onto a solid support. These PANI/Au-NPs
      films were characterized using cyclic voltammetry, copper under potential
      deposition, scanning electron microscopy, atomic force microscopy, and X-ray
      photoelectron spectroscopy. We found that the nanocomposite layers were uniform
      and reproducible. The density of Au-NPs in the monolayer depended on the acidity
      of the subphase as well as on the nanoparticles concentration. Moreover, the Au
      NPs extrude above the PANI and therefore could be used as nanoelectrodes for the
      underpotential deposition (UPD) of copper.

PMID- 20039686
TI  - Controlled growth/patterning of Ni nanohoneycombs on various desired substrates.
AB  - We report a two-step process for the growth/patterning of Ni honeycomb
      nanostructures on various substrates, such as carbon paper, carbon nanotubes
      (CNTs), silicon wafers, and copper grids, via the combination of a sputter
      coating/patterning technique and a replacement reaction solution method. The
      morphology, crystallinity, and chemical composition of the honeycombs were
      analyzed by SEM, TEM, high-resolution TEM, and EDX. These honeycombs are composed
      of numerous nanocells, several tens of nanometers in diameter and with cell wall
      thickness of approximately 10 nm, randomly connecting to each other. The growth
      process of honeycomb nanostructures has been systematically studied.
      Interestingly, the diameter and wall thickness of the cells could be easily tuned
      by simply adjusting the experimental parameters, such as the concentrations and
      cations of metal salts. Additionally, this simple method has been successfully
      extended to synthesize Co nanostructures with well-controlled morphologies, which
      indicates the great potential of this strategy in the synthesis of other metal
      nanostructures on various desired substrates. These metal-substrate composites,
      especially with desired patterns, are expected to be ideal candidates for wide
      application in modern electronic and optoelectronic devices, sensors, fuel cells,
      and energy storage systems.

PMID- 20039687
TI  - Controlled gating of a hemicarcerand by disulfide-dithiol interchange.
AB  - Introduction of a disulfide unit into the linker of a hemicarcerand creates a new
      way to control the entry and exit of guests. When the disulfide bond is reduced
      to two thiols, the "gate" opens, and guests can freely enter the hydrophobic core
      of the hemicarcerand. However, when the gate is closed, the host must be heated
      in the presense of excess guest in order for complexation to result. Several
      novel hemicarceplexes of this type have been synthesized. Molecular mechanics
      calculations are employed to explore the differing stabilities and ease of
      complexation of these host-guest complexes.

PMID- 20039688
TI  - Structure-properties relationships of lithium electrolytes based on ionic liquid.
AB  - Low-melting ionic liquid, IL, based on small aliphatic quaternary ammonium
      cations ([R(1)R(2)R(3)NR](+), where R(1), R(2), R(3) = CH(3) or C(2)H(5), R =
      C(3)H(7), C(4)H(9), C(6)H(13), C(8)H(17), CF(3)C(3)H(6)) and imide anion were
      prepared and characterized. The physicochemical and electrochemical properties of
      these ILs, including melting point, glass transition, and degradation
      temperatures; viscosity; density; ionic conductivity; diffusion coefficient; and
      electrochemical stability, were determined. Heteronuclear Overhauser NMR
      spectroscopy experiments were also performed to point out the presence of pair
      correlation between the different moieties. The LiTFSI addition effect on the IL
      properties was studied with the same methodology. Some nanoscale organization
      with segregation of polar and apolar domains was observed. ILs with small alkyl
      chain length or fluorinated ammonium exhibit very high electrochemical stability
      in oxidation.

PMID- 20039689
TI  - A theoretical investigation on the mechanism of a palladium-mediated formal 6pi
      electrocyclic synthesis of 9,10-dihydrophenanthrenes.
AB  - Recently, a new method for the palladium-catalyzed synthesis of 9,10
      dihydrophenanthrenes was published. A proposed mechanism indicated that the
      reaction proceeds via a disrotatory 6pi electrocyclic ring closing reaction.
      Although the synthetic methodology is excellent for the preparation of 9,10
      phenanthrenes, we propose an alternative mechanism that occurs through an
      intramolecular Heck reaction. Using theoretical calculations, we have
      investigated both mechanisms and find that the intramolecular Heck mechanism is
      lower in energy by 21.3 kcal/mol than the electrocyclic pathway.

PMID- 20039690
TI  - Synthesis and characterization of K(8-x)(H2)ySi46.
AB  - A hydrogen-containing inorganic clathrate with the nominal composition,
      K(7)(H(2))(3)Si(46), has been prepared in 98% yield by the reaction of K(4)Si(4)
      with NH(4)Br. Rietveld refinement of the powder X-ray diffraction data is
      consistent with the clathrate type I structure. Elemental analysis and (1)H MAS
      NMR confirmed the presence of hydrogen in this material. Type I clathrate
      structure is built up from a Si framework with two types of cages where the guest
      species, in this case K and H(2), can reside: a large cage composed of 24 Si, in
      which the guest resides in the 6d position, and a smaller one composed of 20 Si,
      in which the guest occupies the 2a position (cubic space group Pm3n). Potassium
      occupancy was examined using spherical aberration (Cs) corrected scanning
      transmission electron microscopy (STEM). The high-angle annular dark-field
      (HAADF) STEM experimental and simulated images indicated that the K is deficient
      in both the 2a and the 6d sites. (1)H and (29)Si MAS NMR are consistent with the
      presence of H(2) in a restricted environment and the clathrate I structure,
      respectively. FTIR and (29)Si{(1)H} CP MAS NMR results show no evidence for a Si
      H bond, suggesting that hydrogen is present as H(2) in interstitial sites.
      Thermal gravimetry (TG) mass spectrometry (MS) provide additional confirmation of
      H(2) with hydrogen loss at approximately 400 degrees C.

PMID- 20039691
TI  - Lithium furyl and pyridyl amidinates as building blocks in coordination polymers,
      ladder and cage structures.
AB  - Lithium N,N'-bis(trimethylsilyl)heterocyclic amidinate complexes with 3- and 4
      pyridyl and 3-furyl carbon substituents were prepared by addition of the
      corresponding nitriles to LiN(SiMe(3))(2) (LiNTMS(2)) solution. In the presence
      of N,N,N',N' tetramethylethylene diamine (TMEDA), both pyridyl amidinates
      crystallize as coordination polymers with an amidinate-Li-pyridyl backbone. The 4
      pyridyl derivative (7) creates a linear polymer with amidinate-Li-TMEDA units as
      side chains, whereas the 3-pyridyl polymer (6) has a two-dimensional (2D) network
      structure in which TMEDA serves as a cross-linker. Solvation of the reaction
      mixture of 3-furonitrile and LiNTMS(2) with TMEDA affords the monomeric 3-furyl
      amidinate Li TMEDA complex (3). Crystals of the Li(2)O complex {[3-furyl-C
      (NTMS)(2)Li](4).Li(2)O}.C(7)H(8) (4) are obtained from toluene by partial
      hydrolysis of the unsolvated 3-furyl amidinate (2). Degradation of the polymer
      (7) to monomeric units can be achieved by solvation in toluene or by reaction
      with TMS(2)NLi.TMEDA that affords crystals of the complex {NTMS(2)Li.[4-C(5)H(4)N
      C(NTMS)(2)Li.TMEDA]}(2).(NTMS(2)Li.TMEDA) (8). The formation of these aggregates
      can be rationalized by directed substitution of TMEDA with pyridyl moieties and
      by the laddering principle.

PMID- 20039692
TI  - Effect of ancillary ligands on the DNA interaction of [Cr(diimine)3]3+ complexes
      containing the intercalating dipyridophenazine ligand.
AB  - The synthesis of photoluminescent Cr(III) complexes of the type
      [Cr(diimine)(2)(DPPZ)](3+) are described, where DPPZ is the intercalating
      dipyridophenazine ligand, and diimine corresponds to the ancillary ligands bpy,
      phen, DMP, and TMP (where bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, DMP
      = 5,6-dimethyl-1,10-phenanthroline, and TMP = 3,4,7,8-tetramethyl-1,10
      phenanthroline). For TMP, DMP, and phen as ancillary ligands, the complexes have
      also been resolved into their Lambda and Delta optical isomers. A comparison of
      the photophysical and electrochemical properties reveal similar (2)E(g) -->
      (4)A(2g) (O(h)) emission wavelengths and lifetimes, and a variation of 110 mV in
      the (2)E(g) excited state oxidizing power. A detailed investigation has been
      undertaken of ancillary ligand effects on the DNA binding of these complexes with
      a range of polynucleotides. For all four complexes, emission is quenched by the
      addition of calf thymus B-DNA, with the emission lifetime data yielding
      bimolecular quenching rate constants close to the diffusion controlled limit.
      Equilibrium dialysis studies have established a general predilection for AT base
      binding sites, while companion experiments with added distamycin (a selective
      minor groove binder) provide evidence for a minor groove binding preference. For
      the case of [Cr(TMP)(2)(DPPZ)](3+), concomitant equilibrium dialysis and circular
      dichroism measurements have demonstrated very strong enantioselective binding by
      the Lambda optical isomer. The thermodynamics of DNA binding have also been
      explored via isothermal titration calorimetry (ITC). The ITC data establish that
      the primary binding mode for all four Cr(III) complexes is entropically driven, a
      result that is attributed to the highly favorable free energy contribution
      associated with the hydrophobic transfer of the Cr(III) complexes from solution
      into the DNA binding site.

PMID- 20039693
TI  - Effect of polymer hygroscopicity on the phase behavior of amorphous solid
      dispersions in the presence of moisture.
AB  - It has been previously observed that exposure to high relative humidity (RH) can
      induce amorphous-amorphous phase separation in solid dispersions composed of
      certain hydrophobic drugs and poly(vinylpyrrolidone) (PVP). The objective of this
      study was to investigate if this phenomenon occurred in solid dispersions
      prepared using less hygroscopic polymers. Drug-polymer miscibility was
      investigated before and after exposure to high RH using infrared (IR)
      spectroscopy and differential scanning calorimetry (DSC). PVP,
      poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), and hypromellose acetate
      succinate (HPMCAS) were selected as model polymers, and felodipine, pimozide,
      indomethacin, and quinidine were selected as model drugs. Drug-polymer mixing at
      the molecular level was confirmed for all model systems investigated. Moisture
      induced drug-polymer demixing was observed in felodipine-PVPVA, quinidine-PVP,
      quinidine-PVPVA, pimozide-PVPVA, and pimozide-HPMCAS systems, but was absent in
      the other HPMCAS dispersions and for indomethacin-PVPVA. It is concluded that the
      balance between the thermodynamic factors (enthalpy and entropy of mixing) in a
      ternary water-drug-polymer system is the important factor in determining which
      solid dispersion systems are susceptible to moisture-induced amorphous-amorphous
      phase separation. Systems with strong drug-polymer interactions and a less
      hygroscopic polymer will be less susceptible to moisture-induced phase
      separation, while more hydrophobic drugs will be more susceptible to this
      phenomenon even at low levels of sorbed moisture.

PMID- 20039694
TI  - Can graphene be used as a substrate for Raman enhancement?
AB  - Graphene is a monolayer of carbon atoms packed into a two-dimensional (2D)
      honeycomb crystal structure, which is a special material with many excellent
      properties. In the present study, we will discuss the possibility that graphene
      can be used as a substrate for enhancing Raman signals of adsorbed molecules.
      Here, phthalocyanine (Pc), rhodamine 6G (R6G), protoporphyin IX (PPP), and
      crystal violet (CV), which are popular molecules widely used as a Raman probe,
      are deposited equally on graphene and a SiO(2)/Si substrate using vacuum
      evaporation or solution soaking. By comparing the Raman signals of molecules on
      monolayer graphene and on a SiO(2)/Si substrate, we observed that the intensities
      of the Raman signals on monolayer graphene are much stronger than on a SiO(2)/Si
      substrate, indicating a clear Raman enhancement effect on the surface of
      monolayer graphene. For solution soaking, the Raman signals of the molecules are
      visible even though the concentration is low to 10(-8) mol/L or less. What's more
      interesting, the enhanced efficiencies are quite different on monolayer, few
      layer, multilayer graphene, graphite, and highly ordered pyrolytic graphite
      (HOPG). The Raman signals of molecules on multilayer graphene are even weaker
      than on a SiO(2)/Si substrate, and the signals are even invisible on graphite and
      HOPG. Taking the Raman signals on the SiO(2)/Si substrate as a reference, Raman
      enhancement factors on the surface of monolayer graphene can be obtained using
      Raman intensity ratios. The Raman enhancement factors are quite different for
      different peaks, changing from 2 to 17. Furthermore, we found that the Raman
      enhancement factors can be distinguished through three classes that correspond to
      the symmetry of vibrations of the molecule. We attribute this enhancement to the
      charge transfer between graphene and the molecules, which result in a chemical
      enhancement. This is a new phenomenon for graphene that will expand the
      application of graphene to microanalysis and is good for studying the basic
      properties of both graphene and SERS.

PMID- 20039695
TI  - Self-assembled single-phase perovskite nanocomposite thin films.
AB  - Thin films of perovskite-structured oxides with general formula ABO(3) have great
      potential in electronic devices because of their unique properties, which include
      the high dielectric constant of titanates, (1) high-T(C) superconductivity in
      cuprates, (2) and colossal magnetoresistance in manganites. (3) These properties
      are intimately dependent on, and can therefore be tailored by, the
      microstructure, orientation, and strain state of the film. Here, we demonstrate
      the growth of cubic Sr(Ti,Fe)O(3) (STF) films with an unusual self-assembled
      nanocomposite microstructure consisting of (100) and (110)-oriented crystals,
      both of which grow epitaxially with respect to the Si substrate and which are
      therefore homoepitaxial with each other. These structures differ from previously
      reported self-assembled oxide nanocomposites, which consist either of two
      different materials (4-7) or of single-phase distorted-cubic materials that
      exhibit two or more variants. (8-12) Moreover, an epitaxial nanocomposite
      SrTiO(3) overlayer can be grown on the STF, extending the range of compositions
      over which this microstructure can be formed. This offers the potential for the
      implementation of self-organized optical/ferromagnetic or
      ferromagnetic/ferroelectric hybrid nanostructures integrated on technologically
      important Si substrates with applications in magnetooptical or spintronic
      devices.

PMID- 20039696
TI  - RON receptor tyrosine kinase as a target for delivery of chemodrugs by antibody
      directed pathway for cancer cell cytotoxicity.
AB  - Overexpression of the RON receptor tyrosine kinase exists in various cancers and
      contributes to malignant progression. To validate RON as a targeting moiety for
      delivery of chemoagents for enhanced tumor cytotoxicity, immunoliposomes (IL)
      loaded with doxorubicin (Dox) were formulated followed by postinsertion of
      monoclonal antibodies Zt/g4, Zt/c1, or their Fab fragments specific to the RON
      extracellular domains. Flow cytometry analysis showed that Zt/g4 or Zt/c1-IL
      binds to cancer cells and causes RON internalization as evident in confocal
      analysis of intracellular fluorescence intensity. The antibody-directed IL uptake
      by cancer cells is in both dose and time-dependent manners. Studies of
      cytotoxicity of individual IL in vitro against colon or breast cancer cell lines
      revealed that Zt/g4 directed Dox-IL displayed increased cytotoxic activities with
      a significant reduction of IC(50) values. An average of 8-fold increases in
      cytotoxic efficiency was achieved among four cell lines tested. Moreover, Zt/g4
      directed Dox-IL also displayed the effective killing of cancer cells that are
      insensitive to pegylated liposomal doxorubicin. The effect of Zt/c1-Dox-IL was
      not as strong as Zt/g4-Dox-IL, and only moderate activities were observed. IL
      coupled with the Fab fragments of Zt/g4 or Zt/c1 show moderate activities against
      cancer cells. The ineffectiveness seemed to be related to the weak activities of
      the Fab fragments in the induction of RON internalization, which resulted in
      reduced drug uptakes. We conclude that anti-RON antibody-directed drug delivery
      is effective for increased uptake of cytotoxic drugs. Antibody-based RON
      targeting could be developed into a potential therapeutic for treatment of
      malignant cancers.

PMID- 20039697
TI  - Polymer--cisplatin conjugate nanoparticles for acid-responsive drug delivery.
AB  - We report the synthesis of novel acid-responsive therapeutic nanoparticles (NPs)
      with sub-100 nm size consisting of polymer--cisplatin conjugates. The uniqueness
      of these drug delivery polymeric NPs lies in the covalent conjugation of each
      cisplatin drug to the hydrophobic segment of two biocompatible diblock copolymer
      chains through a hydrazone bond, resulting in highly differential drug release
      profile at different environmental acidity. We demonstrate that the synthesized
      polymer--cisplatin conjugates can readily precipitate to form sub-100 nm NPs in
      aqueous solution due to their very low critical micelle concentration (CMC). The
      resulting NPs show well-controlled cisplatin loading yield, excellent acid
      responsive drug release kinetics, and enhanced in vitro cytotoxicity against
      ovarian cancer cells as compared to free cisplatin. As an environmentally
      sensitive drug delivery vehicle, these NPs can potentially minimize the drug loss
      during NP circulation in the blood, where the pH value is neutral, and trigger
      rapid intracellular drug release after the NPs are endocytosed by the target
      cells. This characteristic drug release profile holds the promise to suppress
      cancer cell chemoresistance by rapidly releasing a high dose of chemotherapy
      drugs inside the tumor cells, thereby improving the therapeutic efficacy of the
      drug payload.

PMID- 20039698
TI  - Synthesis of tetrahydropyrroloiminoquinone alkaloids based on electrochemically
      generated hypervalent iodine oxidative cyclization.
AB  - An approach to the synthesis of the tetrahydropyrroloiminoquinone alkaloids has
      been developed and applied to the preparation of N-1-beta-D
      ribofuranosyltetrahydropyrroloiminoquinones. The strategy utilizes oxidative
      cyclization of aryl-methoxyamides by hypervalent iodine to construct the
      quinoline framework shared by members of this alkaloid family. The hypervalent
      iodine oxidant is generated in situ by anodic oxidation of iodobenzene.

PMID- 20039699
TI  - First application of an efficient and versatile ligand for copper-catalyzed cross
      coupling reactions of vinyl halides with N-heterocycles and phenols.
AB  - 2-Pyridin-2-yl-1H-benzoimidazole L3 is presented as a new, efficient, and
      versatile bidentate N-donor ligand suitable for the copper-catalyzed formation of
      vinyl C-N and C-O bonds. This inexpensive and easily prepared ligand facilitates
      copper-catalyzed cross-coupling reactions of alkenyl bromides and iodides with N
      heterocycles and phenols to afford the desired cross-coupled products in good to
      excellent yields with full retention of stereochemistry. This method is
      particularly noteworthy given its efficiency, that is, mild reaction conditions,
      low catalyst loading, simplicity, versatility, and exceptional level of
      functional group tolerance.

PMID- 20039700
TI  - Activated nickel platform for electrochemical sensing of phosphate.
AB  - We report here a highly selective enzymeless approach for the determination of
      phosphate (PO(4)(3-)) by flow injection analysis (FIA). In this system, the
      activation of barrel plated nickel electrode (Ni-BPE) in alkaline media to form a
      Ni(OH)(2)/NiO(OH) film was found to trigger the adsorption of phosphate at the
      electrode surface. Based on the suppressed current of the electrocatalytic
      oxidation of glucose at the activated Ni-BPE in 0.1 M NaOH solution caused by
      adsorption of phosphate, we develop an FIA detection scheme for the determination
      of phosphate. Under the optimized conditions of flow rate = 300 microL/min and
      detection potential = 0.55 V vs Ag/AgCl with 25 microM glucose in 0.1 M NaOH as
      carrier solution, the calibration curve showed a linear range up to 1 mM.
      Possible interferences from the coexisting ions were also investigated. The
      results demonstrated that sensor could be used for the determination of phosphate
      in the presence of nitrate, chloride, sulfate, acetate, oxalate, carbonate, and
      some anionic species of toxicological and environmental interest, such as
      chlorate, chromate, and arsenate ions. The electrode can be effectively
      regenerated without extra treatment under the hydrodynamic condition. For eight
      continuous injections of 40 microM PO(4)(3-), a relative standard deviation of
      0.28% was obtained, indicating good reproducibility of the proposed method. The
      detection limit (S/N = 3) was calculated as 0.3 microM.

PMID- 20039701
TI  - Design and synthesis of a fluorescent probe for Zn2+, 5,7-bis(N,N
      dimethylaminosulfonyl)-8-hydroxyquinoline-pendant 1,4,7,10-tetraazacyclododecane
      and Zn2+-dependent hydrolytic and Zn2+-independent photochemical reactivation of
      its benzenesulfonyl-caged derivative.
AB  - We previously reported on a 8-quinolinol-pendant cyclen (L(5)) as a Zn(2+)
      fluorophore (cyclen = 1,4,7,10-tetraazacyclododecane) and its caged derivative, 8
      (benzenesulfonyloxy)-5-(N,N-dimethylaminosulfonyl)quinolin-2-ylmethyl-pendant
      cyclen (BS-caged-L(5)), which can be reactivated by hydrolysis of benzenesulfonyl
      group upon complexation with Zn(2+) at neutral pH to give a 1:1 Zn(2+)-L(5)
      complex (Zn(H(-1)L(5))). We report herein on the synthesis of 5,7-bis(N,N
      dimethylaminosulfonyl)-8-hydroxyquinolin-2-ylmethyl-pendant cyclen (L(6)) and its
      caged derivative (BS-caged-L(6)) for more sensitive and more efficient cell
      membrane permeability than those of L(5) and BS-caged-L(5). By potentiometric pH,
      (1)H NMR, and UV-vis spectroscopic titrations, the deprotonation constants pK(a1)
      pK(a6) of H(5)L(6) were determined to be <2, <2, <2, 2.5 +/- 0.1 (for the 8-OH
      group of the quinoline moiety), 9.7 +/- 0.1, and 10.8 +/- 0.1 at 25 degrees C
      with I = 0.1 (NaNO(3)). The results of (1)H NMR, potentiometric pH, UV-vis, and
      fluorescent titrations showed that L(6) rapidly forms a 1:1 complex with Zn(2+)
      (Zn(H(-1)L(6))), the dissociation constant of which is 50 fM at pH 7.4. The
      fluorescent emission of Zn(H(-1)L(6)) at 478 nm is 32 times as large as that of
      L(6) (excitation at 370 nm), and the fluorescent quantum yield of Zn(H(-1)L(6))
      (Phi(F) = 0.41) is much greater than that of Zn(H(-1)L(5)) (Phi(F) = 0.044). The
      BS-caged-L(6) was reactivated by hydrolysis of the benzenesulfonyl moiety more
      rapidly (completes in 30 min at pH 7.4 at 37 degrees C) than BS-caged-L(5),
      presumably enabling the practical detection of Zn(2+) in sample solutions and
      living cells. The photochemical deprotection of BS-caged-L(6) and the cell
      membrane permeability of L(6) and BS-caged-L(6) are also described.

PMID- 20039702
TI  - A two-dimensional metal-organic framework based on a ferromagnetic pentanuclear
      copper(II).
AB  - The hydrothermal reaction of CuSO(4), 1,2-benzenedicarboxylate (phth), and 1,2
      bis(imidazol-1-yl)ethane (bime) yields the two-dimensional metal-organic
      framework {[Cu(5)(bime)(mu(3)-OH)(2)(phth)(4)](H(2)O)(2)}(n) (1), which is based
      on the pentanuclear copper(II) cluster [Cu(5)(mu(3)-OH)(2)(phth)(4)] and shows
      dominant ferromagnetic interactions within the pentanuclear cluster.

PMID- 20039703
TI  - Kinetics of the transfer of ubiquitin from UbcH7 to E6AP.
AB  - Prior to substrate ubiquitination by HECT-E3 ligases, ubiquitin must first be
      activated by E1 and then transferred via a series of transthiolation reactions
      from E1 to E2 and from E2 to E3. We have measured the rate constants and binding
      affinities underlying the transfer of ubiquitin from E2 UbcH7 to the HECT domain
      of E3 E6AP. We show that charged UbcH7 and free UbcH7 bind E6AP with similar
      affinities and that at 37 degrees C the second-order rate constant for the
      reaction (k(cat)/K(m)) equals approximately 2.3 x 10(5) M(-1) s(-1). The measured
      parameters place limits on substrate-E6AP binding lifetimes required for
      processive polyubiquitination.

PMID- 20039706
TI  - Phosphoprotein changes during sperm capacitation.

PMID- 20039705
TI  - Global proteomic analysis of the insoluble, soluble, and supernatant fractions of
      the psychrophilic archaeon Methanococcoides burtonii. Part I: the effect of
      growth temperature.
AB  - The response of the cold-adapted (psychrophilic) methanogenic archaeon
      Methanococcoides burtonii to growth temperature was investigated using
      differential proteomics (postincorporation isobaric labeling) and tandem liquid
      chromatography-mass spectrometry (LC/LC-MS/MS). This is the first proteomic study
      of M. burtonii to include techniques that specifically enrich for both surface
      and membrane proteins and to assess the effects of growth temperature (4 vs 23
      degrees C) and carbon source (trimethylamine vs methanol) on cellular protein
      levels. Numerous surface layer proteins were more abundant at 4 degrees C,
      indicating an extensive remodeling of the cell envelope in response to low
      temperature. Many of these surface proteins contain domains associated with cell
      adhesion. Within the cell, small proteins each composed of a single TRAM domain
      were recovered as important cold adaptation proteins and might serve as RNA
      chaperones, in an analogous manner to Csp proteins (absent from M. burtonii).
      Other proteins that had higher abundances at 4 degrees C can be similarly tied to
      relieving or resolving the adverse affects of cold growth temperature on
      translational capacity and correct protein folding. The proteome of M. burtonii
      grown at 23 degrees C was dominated by oxidative stress proteins, as well as a
      large number of integral membrane proteins of unknown function. This is the first
      truly global proteomic study of a psychrophilic archaeon and greatly expands
      knowledge of the cellular mechanisms underpinning cold adaptation in the Archaea.

PMID- 20039704
TI  - Novel Ser/Thr protein phosphatase 5 (PP5) regulated targets during DNA damage
      identified by proteomics analysis.
AB  - The DNA damage response likely includes a global phosphorylation signaling
      cascade process for sensing the damaged DNA condition and coordinating responses
      to cope with and repair the perturbed cellular state. We utilized a label-free
      liquid chromatography-mass spectrometry approach to evaluate changes in protein
      phosphorylation associated with PP5 activity during the DNA damage response.
      Biological replicate analyses of bleomycin-treated HeLa cells expressing either
      WT-PP5 or mutant inactive PP5 lead to the identification of six potential target
      proteins of PP5 action. Four of these putative targets have been previously
      reported to be involved in DNA damage responses. Using phospho-site specific
      antibodies, we confirmed that phosphorylation of one target, ribosomal protein
      S6, was selectively decreased in cells overexpressing catalytically inactive PP5.
      Our findings also suggest that PP5 may play a role in controlling translation and
      in regulating substrates for proline-directed kinases, such as MAP kinases and
      cyclin-dependent protein kinases that are involved in response to DNA damage.

PMID- 20039707
TI  - Factors controlling alkylbenzene and tetrachloroethene desorption from municipal
      solid waste components.
AB  - Desorption rates of toluene, o-xylene and tetrachloroethene from individual
      municipal solid waste components [high-density polyethylene (HDPE); poly(vinyl
      chloride) (PVC); office paper; newsprint; and rabbit food, a model food and yard
      waste] were determined. Effects of sorbent and sorbate properties, solvent
      composition (ultrapure water, acidogenic and methanogenic leachates), and contact
      time ("aging") on desorption rates were evaluated. Hydrophobic organic
      contaminant (HOC) desorption from PVC and HDPE could be described with a single
      parameter polymer diffusion model. In contrast, a three-parameter, biphasic
      polymer diffusion model was required to describe HOC desorption rates from
      biopolymer composites. In general, HOC desorption rates from plastics were rapid
      for HDPE (D = 10(-10) cm(2)/s), a rubbery polymer, but slower for PVC (D = 10(
      13)-10(-14) cm(2)/s), a glassy polymer. For biopolymer composites, a large
      fraction of sorbed HOCs was rapidly released (D(r) = 10(-9)-10(-10) cm(2)/s)
      while the remaining fraction desorbed slowly (D(s) = 10(-11)-10(-16) cm(2)/s).
      The toluene desorption rate from PVC was 1 order of magnitude faster in
      acidogenic leachate than in either ultrapure water or methanogenic leachate, a
      result that was primarily attributed to the plasticizing effect of volatile fatty
      acids in acidogenic leachate. For biopolymer composites, small increases in the
      slowly desorbing HOC fraction were observed with increasing aging time.

PMID- 20039708
TI  - Levels and seasonal variability of pesticides in the rural atmosphere of Southern
      Ontario.
AB  - Air samples were collected continuously in Egbert, Ontario, which is in a rural
      agricultural area north of Toronto, between March 2006 and September 2007 and
      analyzed for pesticides of both current and historic use. The fungicide
      chlorothalonil was present in highest abundance with levels exceeding 2000 pg x
      m(-3) in the summer. Almost as abundant, with summer time concentrations around
      400 to 600 pg x m(-3), were the herbicides atrazine, alachlor, and metolachlor.
      Other pesticides in current use, such as trifluralin, pendimethalin,
      chlorpyrifos, endosulfan, and disulfoton were consistently present at levels
      approximately 1 order of magnitude lower. Concentrations of banned pesticides
      (chlordanes and hexachlorocyclohexane) were generally below 10 pg x m(-3), except
      for hexachlorobenzene, which was present at the global average of approximately
      50 pg x m(-3). These levels and the fact that they are generally lower than what
      has been reported for the area previously are in agreement with pesticide usage
      data for Ontario. Only the concentrations of chlorothalonil, chlorpyrifos, and
      HCB were correlated with air mass origin, as determined by back trajectory
      analysis. All pesticides had higher levels during the growing season compared to
      those in winter, but the ratio of concentrations during the different seasons is
      much higher for the pesticides in current use. That ratio may aid in
      distinguishing seasonal variability caused by pesticide application during the
      growing season from that caused by temperature-driven revolatilization. Higher
      concentrations of the banned pesticides during 2007 compared to those in 2006 may
      be due to higher volatilization rates caused by higher surface temperatures
      consistent with the El Nino Southern Oscillation.

PMID- 20039709
TI  - Time-resolved fluoroimmunoassay as an advantageous approach for highly efficient
      determination of sulfonamides in environmental waters.
AB  - Using monoclonal antibodies labeled with Eu(3+) chelates, time-resolved
      fluoroimmunoassay (TRFIA) methods were developed for the determination of trace
      sulfamethazine (SMZ), sulfa-methoxazole (SMX), and sulfadiazine (SDZ) in
      environmental waters. Under the optimized conditions, the developed methods
      offered (i) low detection limits (9.8 ng/L SMZ, 6.1 ng/L SMX, and 5.4 ng/L SDZ,
      based on 90% inhibition) which were about 1 order of magnitude lower than that of
      the enzyme-linked immunosorbent assay (ELISA), (ii) high selectivity with no
      cross-reactivity (<0.05%) to similarly structured sulfonamides; (iii) high
      tolerance to variation of the sample pH (6.0-9.0) and salinity (0-100 mM), as
      well as the presence of humic acid (0-100 mg/L DOC) and heavy metals (0-1 mg/L
      concentration each of Cu(2+), Cd(2+), Hg(2+), Pb(2+), and As(V)) in the samples,
      and (iv) direct determination with low cost, high sample throughput, and low
      sample consumption (50-100 microL). The proposed TRFIA procedures were applied to
      determine sulfonamides in a variety of surface water and wastewater samples
      without sample pretreatment other than filtration. The satisfactory recoveries
      (64-127%) and reproducibilities (CV = 0.2-16%) achieved, as well as the good
      agreement with those given by liquid chromatography-tandem mass spectroscopy and
      ELISA methods, demonstrated the applicability of the proposed TRFIA methods for
      routine screening/quantification of sulfonamides in environmental waters.

PMID- 20039710
TI  - Infrared spectrum of the propargyl peroxyl radical, HC[triple bond]C-CH2OO X
      2A''.
AB  - When the propargyl radical, HCCCH(2), and O(2) are codeposited onto a cold argon
      matrix, a chemical reaction ensues; infrared absorption spectra reveal the
      formation of the propargyl peroxyl radical: HC=C-CH(2) X (2)B(1) + O(2) --> trans
      HC=C-CH(2)OO X (2)A. We do not observe the isomeric adduct, CH(2)=C=CHOO X
      (2)A''. The propargyl radicals are produced by a hyperthermal nozzle while a
      second nozzle alternately fires bursts of O(2)/Ar at the 20 K matrix. The
      absorption spectra of the radicals are measured using a Fourier transform
      infrared spectrometer. We observe 13 of the 18 fundamental infrared bands of the
      propargyl peroxyl radical in an Ar matrix at 20 K. The experimental frequencies
      (cm(-1)) of trans-HC[triple bond]C-CH(2)OO X (2)A'' are assigned. The a' modes
      are nu(1) = 3326, nu(2) = 2960, nu(3) = 2148, nu(4) = 1440, nu(5) = 1338, nu(6) =
      1127, nu(7) = 982, nu(8) = 928, nu(9) = 684, and nu(10) = 499 cm(-1), while the
      a'' modes are nu(14) = 1218, nu(15) = 972, and nu(16) = 637 cm(-1). Linear
      dichroism spectra were measured with photo-oriented HCCCH(2)OO radical samples to
      establish the experimental polarizations of several vibrational bands. The
      experimental frequencies (nu) for the propargyl peroxyl radical are compared to
      the anharmonic frequencies (upsilon) resulting from electronic structure
      calculations. We have used CBS-QB3 electronic structure calculations to estimate
      the peroxyl bond energies: DeltaH(298)(trans-HC[triple bond]CCH(2)-OO -->
      CH(2)CCH X (2)B(1) + O(2)) = 19 +/- 1 kcal mol(-1) and DeltaH(298)(trans
      CH(2)=C=CH-OO --> CH(2)CCH X (2)B(1) + O(2)) = 21 +/- 1 kcal mol(-1). The
      experimental thermochemistry for C(3)H(3) reacting with oxygen has been
      reanalyzed as Delta(rxn)H(298)(HCCCH(2) + O(2) --> CH(2)=C=O + HCO) = -83 +/- 3
      kcal mol(-1); Delta(rxn)H(298)(HCCCH(2) + O(2) --> CH(3)CO + CO) = -111 +/- 3
      kcal mol(-1); Delta(rxn)H(298)(HCCCH(2) + O(2) --> CH(2)CHO + CO) = -106 +/- 4
      kcal mol(-1); Delta(rxn)H(298)(HCCCH(2) + O(2) --> HCHO + HCCO) = -67 +/- 4 kcal
      mol(-1); Delta(rxn)H(298)(HCCCH(2) + O(2) --> CH(2)CH + CO(2)) = -105 +/- 3 kcal
      mol(-1).

PMID- 20039711
TI  - Reduction of hydrogen peroxide by glutathione peroxidase mimics: reaction
      mechanism and energetics.
AB  - The reaction mechanism for the reduction of hydrogen peroxide by N,N
      dimethylbenzylamine diselenide, its selenol analogue, and the charged analogues
      of the diselenide and selenol are elucidated using reliable electronic structure
      techniques. It is found that the reaction using the diselenide has a large Gibbs
      energy barrier of 173.5 kJ/mol. The cationic diselenide, with both amines
      protonated, shows a lower barrier of 103.5 kJ/mol. Both diselenide species show
      significant Se-Se bond lengthening upon oxidation. An unusual two-step mechanism
      is found for the selenol with barriers of 136.3 and 141.9 kJ/mol, respectively,
      showing that it is unlikely that the selenol is the active form. The zwitterion,
      selenolate, and protonated amine analogues of the selenol show one-step reactions
      with energy barriers of 82.7, 92.7, and 102.3 kJ/mol, respectively. The
      zwitterion of the selenol shows the most favorable reaction energies, which is in
      good agreement with proposed mechanisms for this reaction.

PMID- 20039712
TI  - Comprehensive study of the hydration and dehydration reactions of carbon dioxide
      in aqueous solution.
AB  - The reversible interactions of dissolved CO(2) with H(2)O and OH(-) to form
      H(2)CO(3) and HCO(3)(-) in aqueous solution have been investigated using
      spectrophotometric stopped-flow measurements. The progress of the reactions was
      monitored via indicators coupled to the pH changes during the reactions. The
      study, involving global analysis of the complete data set, spanned the
      temperature range 6.6-42.8 degrees C and resulted in the evaluation of all rate
      and equilibrium constants as well as activation parameters for the kinetic data
      and the reaction enthalpies and entropies for the equilibrium constants.

PMID- 20039713
TI  - Sources and pathways of polycyclic aromatic hydrocarbons transported to Alert,
      the Canadian High Arctic.
AB  - A probabilistic function (integrated source contribution function, ISCF) based on
      backward air mass trajectory calculation was developed to track sources and
      atmospheric pathways of polycyclic aromatic hydrocarbons (PAHs) to the Canadian
      High Arctic station of Alert. In addition to the movement of air masses, the
      emission intensities at the sources and the major processes of partition,
      indirect photolysis, and deposition occurring on the way to the Arctic were
      incorporated into the ISCF. The predicted temporal trend of PAHs at Alert was
      validated by measured PAH concentrations throughout 2004. The PAH levels in the
      summer are orders of magnitude lower than those in the winter and spring when
      long-range atmospheric transport events occur more frequently. PAHs observed at
      Alert are mostly from East Asia (including Russia Far East), North Europe
      (including European Russia), and North America. These sources account for 25, 45,
      and 27% of PAHs atmospheric level at Alert, respectively. Source regions and
      transport pathways contributing to the PAHs contamination in the Canadian High
      Arctic vary seasonally. In the winter, Russia and Europe are the major sources.
      PAHs from these sources travel eastward and turn to the north at approximately
      120 degrees E before reaching Alert, in conjunction with the well-known Arctic
      haze events. In the spring, PAHs from Russia and Europe first migrate to the west
      and then turn to the north at 60 degrees W toward Alert. The majority of PAHs in
      the summer are from northern Canada where they are carried to Alert via low-level
      transport pathways. In the fall, 70% of PAHs arriving at Alert are delivered from
      North American sources.

PMID- 20039715
TI  - Stereodynamics at the gas-liquid interface: orientation and alignment of CO2
      scattered from perfluorinated liquid surfaces.
AB  - Rotational orientation/alignment dynamics of CO(2) scattered from a
      perfluorinated polyether (PFPE) liquid surface has been investigated via direct
      absorption experimental studies and theoretical molecular dynamics (MD)
      simulations. Experimentally, polarization modulation of a single mode diode laser
      is combined with lock-in detection to measure circular/linear IR polarizance due
      to CO(2) scattering from the surface at theta(inc) = 60 degrees and E(inc) =
      10.6(8) kcal/mol and probed over a series of final scattering angles. The
      differential absorption intensities are related through Fano-Macek theory to the
      three lowest multipole moments (A(0), A(2+), and O(1-)) which describe
      collisionally induced orientation and alignment at the liquid surface. The total
      scattering population reflects both trapping-desorption (TD) and impulsive
      scattering (IS) components, with a strong positive anisotropy in the M(J)
      distribution that indicates preferential CO(2) scattering from the surface with a
      forward (i.e., "topspin") sense of end-over-end tumbling. Theoretical trajectory
      simulations provide 3D CO(2) flux and J state distributions scattering from
      fluorinated self-assembled monolayers (F-SAMs) and are compared with experimental
      results as a function of final rotational state. Specifically, trends in the
      theoretical orientation/alignment moments are in remarkable agreement over the
      full range of J states but with values consistently overpredicted by nearly 2
      fold, which may reflect a higher level of local ordering for F-SAMS vs a gas-PFPE
      liquid interface.

PMID- 20039714
TI  - Efavirenz binding to HIV-1 reverse transcriptase monomers and dimers.
AB  - Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV
      1 reverse transcriptase (RT) used for the treatment of AIDS. RT is a heterodimer
      composed of p66 and p51 subunits; p51 is produced from p66 by C-terminal
      truncation by HIV protease. The monomers can form p66/p66 and p51/p51 homodimers
      as well as the p66/p51 heterodimer. Dimerization and efavirenz binding are
      coupled processes. In the crystal structure of the p66/p51-EFV complex, the drug
      is bound to the p66 subunit. The binding of efavirenz to wild-type and
      dimerization-defective RT proteins was studied by equilibrium dialysis,
      tryptophan fluorescence, and native gel electrophoresis. A 1:1 binding
      stoichiometry was determined for both monomers and homodimers. Equilibrium
      dissociation constants are approximately 2.5 microM for both p66- and p51-EFV
      complexes, 250 nM for the p66/p66-EFV complex, and 7 nM for the p51/p51-EFV
      complex. An equilibrium dissociation constant of 92 nM for the p66/p51-EFV
      complex was calculated from the thermodynamic linkage between dimerization and
      inhibitor binding. Binding and unbinding kinetics monitored by fluorescence were
      slow. Progress curve analyses revealed a one-step, direct binding mechanism with
      association rate constants k(1) of approximately 13.5 M(-1) s(-1) for monomers
      and heterodimer and dissociation rate constants k(-1) of approximately 9 x 10(-5)
      s(-1) for monomers. A conformational selection mechanism is proposed to account
      for the slow association rate. These results show that efavirenz is a slow, tight
      binding inhibitor capable of binding all forms of RT and suggest that the NNRTI
      binding site in monomers and dimers is similar.

PMID- 20039716
TI  - Performance of relativistic effective core potentials in DFT calculations on
      actinide compounds.
AB  - Density functional theory (DFT) calculations using relativistic effective core
      potentials (RECPs) have emerged as a robust and fast method of calculating the
      structural parameters and energy changes of the thermochemical reactions of
      actinide complexes. A comparative investigation of the performance of the
      Stuttgart small-core and large-core RECPs in DFT calculations has been carried
      out. The vibrational frequencies and reaction enthalpy changes of several
      uranium(VI) compounds computed using these RECPs were compared to those obtained
      using DFT and a four-component one-electron scalar relativistic approximation of
      the full Dirac equation with large all-electron basis sets (AE). The relativistic
      AE method is a full solution of the Dirac equation with all spin components
      separated out. This method gives the "correct" answer (with respect to scalar
      relativity) which should be closest to experimental values when an adequate
      density functional is used and in the absence of significant spin-orbit effects.
      The small-core RECP always show better agreement with the four-component scalar-
      relativistic AE method than the large-core RECP. We conclude that the 5s, 5p, and
      5d orbitals are of great importance in determining the chemistry of actinide
      complexes. Instances in which large-core RECPs give better agreement with
      experimental data are attributed to either experimental uncertainties or error
      cancellations.

PMID- 20039717
TI  - Laser spectroscopy of conformationally constrained alpha/beta-peptides: Ac-ACPC
      Phe-NHMe and Ac-Phe-ACPC-NHMe.
AB  - Single-conformation ultraviolet and infrared spectra have been recorded under the
      isolated molecule conditions of a supersonic expansion for three conformationally
      constrained alpha/beta-peptides, Ac-L-Phe-ACPC-NHMe (alpha(L)beta(ACPC)), Ac-ACPC
      L-Phe-NHMe (beta(ACPC)alpha(L)), and Ac-ACPC-D-Phe-NHMe (beta(ACPC)alpha(D)).
      These three molecules are close analogues of the hAla-containing alpha/beta
      peptide counterparts Ac-L-Phe-beta(3)-hAla-NHMe, Ac-beta(3)-hAla-L-Phe-NHMe, and
      Ac-beta(3)-hAla-D-Phe-NHMe, which have been studied recently by James et al. (J.
      Am. Chem. Soc. 2009, 131, 6574). Incorporation of the beta-amino acid trans-2
      aminocyclopentanecarboxylic acid (ACPC) constrains the beta-peptide backbone via
      the cyclopentane ring, producing clear changes in the conformational preferences
      relative to the unconstrained analogues. The conformational control is manifested
      most obviously in the complete absence of C6 H-bonded rings, which were dominant
      in the unconstrained alpha/beta-peptides. The most stable C6 ring structure (C6a)
      in the absence of the ACPC ring cannot be formed in its presence, while a
      secondary C6 ring (C6b) has its energy destabilized by approximately 20 kJ/mol.
      In alpha(L)beta(ACPC), the preference for C5 structures in the N-terminal
      position, combined with the strong preference for C8 structures in the beta
      peptide subunit, leads to the observation of two C5/C8 bifurcated double ring
      conformers. Both C8/C7 sequential double rings and C11 single rings are observed
      in beta(ACPC)alpha(L) and beta(ACPC)alpha(D). Here, the ACPC ring selectively
      stabilizes the C8a ring over other possible C8 structures. Finally, the combined
      evidence from IR and UV spectra lead to tentative assignments for diastereomeric
      pairs, exhibiting small but understandable shifts in the IR and UV spectra
      induced by the change in chirality at the alpha-peptide chiral center.

PMID- 20039718
TI  - Mapping the network of pathways of CO diffusion in myoglobin.
AB  - The pathways of diffusion of a CO molecule inside a myoglobin protein and toward
      the solvent are investigated. Specifically, the three-dimensional potential of
      mean force (PMF or free energy) of the CO molecule position inside the protein is
      calculated by using the single-sweep method in concert with fully resolved
      atomistic simulations in explicit solvent. The results are interpreted under the
      assumption that the diffusion of the ligand can be modeled as a navigation on the
      PMF in which the ligand hops between the PMF local minima following the minimum
      free energy paths (MFEPs) with rates set by the free energy barriers that need to
      be crossed. Here, all the local minima of the PMF, the MFEPs, and the barriers
      along them are calculated. The positions of the local minima are in good
      agreement with all the known binding cavities inside the protein, which indicates
      that these cavities may indeed serve as dynamical traps inside the protein and
      thereby influence the binding process. In addition, the MFEPs connecting the
      local PMF minima show a complicated network of possible pathways of exit of the
      dissociated CO starting from the primary docking site, in which the histidine
      gate is the closest exit from the binding site for the ligand but it is not the
      only possible one.

PMID- 20039719
TI  - Reactive sulfur species: kinetics and mechanism of the oxidation of aryl
      sulfinates with hypochlorous acid.
AB  - The mechanism of oxidation of ArSO(2)(-) (PhSO(2)(-) and 5-sulfinato-2
      nitrobenzoic acid = TNBO(2)(1-/2-)) with HOCl/OCl(-) has been investigated using
      the kinetic method. In contrast to previous reports for PhSO(2)(-) (for which it
      was suggested that OCl(-) and not HOCl was the reactant), the reaction proceeds
      through a conventional pathway: nucleophilic attack by ArSO(2)(-) on HOCl with
      concomitant Cl(+) transfer to give a sulfonyl chloride intermediate (ArSO(2)Cl),
      which we have identified spectrophotometrically. Remarkably, the rate constant
      for the reaction of HOCl with ArSO(2)(-) is on the order of 10(9) M(-1) s(-1),
      larger than the rate constants for corresponding thiolates, and is nearly
      diffusion-controlled. In contrast, the rate constant for the reaction of OCl(-)
      with ArSO(2)(-) is approximately 7 orders of magnitude smaller.

PMID- 20039720
TI  - Structure and hydrogen-bond vibrations of water complexes of azaaromatic
      compounds: 7-(3'-pyridyl)indole.
AB  - Complexes with water have been studied in the regime of supersonic jet isolation
      for 7-(3'-pyridyl)indole, a bifunctional molecule possessing hydrogen bond donor
      and acceptor groups. Two rotameric forms, syn and anti, are possible, of which
      only the former is able to form cyclic hydrogen bonds with protic solvents.
      Infrared-induced ion depletion spectroscopy was used to obtain vibrational
      patterns for 1:1 and 1:2 complexes in the hydrogen bond stretching region. The
      analysis of the spectra, supported by DFT calculations, revealed that for both
      stoichiometries the dominant forms correspond to cyclic, doubly or triply
      hydrogen-bonded species. The frequencies of NH...O, OH...N, and OH...O stretching
      vibrations were compared with the literature data to assess the strength of
      single vs multiple hydrogen bonds. Several new assignments and reassignments were
      proposed.

PMID- 20039721
TI  - Rapid, absolute, and simultaneous quantification of specific pathogenic strain
      and total bacterial cells using an ultrasensitive dual-color flow cytometer.
AB  - This paper describes a rapid and sensitive strategy for the absolute and
      simultaneous quantification of specific pathogenic strain and total bacterial
      cells in a mixture. A laboratory-built compact, high-sensitivity, dual channel
      flow cytometer (HSDCFCM) was modified to enable dual fluorescence detection. A
      bacterial cell mixture comprising heat-killed pathogenic Escherichia coli E. coli
      O157:H7 and harmless E. coli DH5alpha was used as a model system. Pathogenic E.
      coli O157:H7 cells were selectively labeled by red fluorescent probe via antibody
      antigen interaction, and all bacterial cells were stained with membrane-permeable
      nucleic acid dye that fluoresces green. When each individual bacterium passes
      through the interrogating laser beam, E. coli O157:H7 emits both red and green
      fluorescence, while E. coli DH5alpha exhibits only green fluorescence. Because
      the fluorescence burst generated from each individual bacterial cell was easily
      distinguished from the background, accurate enumeration and consequently absolute
      quantification were achieved for both pathogenic and total bacterial cells. By
      using this strategy, accurate counting of bacteria at a density above 1.0 x 10(5)
      cells/mL can be accomplished with 1 min of data acquisition time after
      fluorescent staining. Excellent correlation between the concentrations measured
      by the HSDCFCM and the conventional plate-counting method were obtained for pure
      cultured E. coli O157:H7 (R(2) = 0.9993) and E. coli DH5alpha (R(2) = 0.9998).
      Bacterial cell mixtures with varying proportions of E. coli O157:H7 and E. coli
      DH5alpha were measured with good ratio correspondence. We applied the established
      approach to detecting artificially contaminated drinking water samples; E. coli
      O157:H7 of 1.0 x 10(2) cells/mL were accurately quantified upon sample
      enrichment. It is believed that the proposed method will find wide applications
      in many fields demanding bacterial identification and quantification.

PMID- 20039722
TI  - Cr stable isotopes as indicators of Cr(VI) reduction in groundwater: a detailed
      time-series study of a point-source plume.
AB  - Chromium stable isotope ratios show promise as indicators of Cr(VI) reduction in
      groundwater, but no published study has yet demonstrated that expected
      relationships between (53)Cr/(52)Cr and Cr(VI) concentration, position, and time
      occur in an actual groundwater plume. We present an extensive data set from a
      point-source plume in Berkeley, CA; data extend over 5 years and 14 locations
      covering the entire plume. We interpret the data using a Rayleigh distillation
      model with an effective fractionation factor that incorporates an intrinsic
      fractionation factor determined from incubations of site sediments and accounts
      for reservoir effects in the restricted subsurface zones where Cr(VI) reduction
      is thought to occur. The groundwater (53)Cr/(52)Cr and Cr(VI) concentration data
      are consistent with a scenario where the system has reached a steady state:
      Cr(VI) reduction continues, the extent of reduction at any point is constant over
      time, reduction proceeds to completion at the downgradient edge of the plume, and
      the plume is no longer advancing. The overall consistency of the results with a
      reasonable model for the site supports the use of Cr isotope-based estimates of
      reduction, but we discuss current uncertainties and limitations of the approach
      as well.

PMID- 20039723
TI  - Quantum chemical investigations on intraresidue carbonyl-carbonyl contacts in
      aspartates of high-resolution protein structures.
AB  - The folding and stability of a polypeptide chain are due to many different and
      simultaneous noncovalent interactions. Recent studies have observed several novel
      and counterintuitive contacts in protein structures, and the nature of
      interactions due to such contacts is yet to be fully elucidated. We have
      identified carbonyl-carbonyl intraresidue contacts in 102 Asp residues from a
      data set of high-resolution protein structures. At the outset, it appears that
      such close approach of two carbonyl oxygen atoms is energetically not favorable.
      We have carried out ab initio quantum chemical calculations on 10 representative
      examples of self-contacting Asp residues from different regions of the
      Ramachandran map. Potential energy scan using three levels of theory (HF, B3LYP,
      and MP2) and two basis sets (6-31+G* and 6-31++G**) was performed by varying the
      side-chain dihedral angle chi(1) while keeping all other parameters corresponding
      to that observed in the protein structures. We also calculated interaction
      energies by considering the surrounding interacting residues and water molecules.
      Our results show that the energy difference between a self-contacting Asp residue
      from the crystal structures and the minimum energy conformations is about 10-15
      kcal/mol. This small energy difference is compensated by its interactions with
      the surrounding residues and water molecules as observed in the interaction
      energy analysis. The results are independent of the levels of theory used. The
      contacting carbonyl-carbonyl groups adopt a sheared parallel motif orientation
      which helps to expose both the backbone and side-chain carbonyl oxygen atoms and
      enable them to participate in tertiary interactions. Natural bond orbital
      calculations indicate that carbonyl-carbonyl groups in self-contacting Asp
      residues interact through n --> pi* electron delocalization. The geometry
      analysis and nature of chemical interactions together explain the rationale for
      the existence of such Asp residues in protein structures and their importance in
      the protein stability.

PMID- 20039724
TI  - Energy-efficient photodegradation of azo dyes with TiO(2) nanoparticles based on
      photoisomerization and alternate UV-visible light.
AB  - Herein, we demonstrated a UV-vis light alternate photocatalysis (UVLAP) strategy
      in the photodegradation of azo dyes. The UVLAP of azo dyes over TiO(2) catalysts
      exhibited significantly higher energy efficiency than the conventional UV process
      by 40%, which was attributed to the photoisomerization of azo dyes and the
      resulting diversity of dyes' cis and trans states in interfacial properties,
      including conductance and spatial effects. This UVLAP strategy could contribute
      to the energy-saving photodegradation of azo dyes and other pollutants with
      photoisomerization properties and facilitate the practical application of TiO(2)
      in the environmental remediation.

PMID- 20039726
TI  - Biology meets geology through chemistry.

PMID- 20039725
TI  - Photocytotoxic oxovanadium(IV) complexes showing light-induced DNA and protein
      cleavage activity.
AB  - Oxovanadium(IV) complexes [VO(L)(B)]Cl(2) (1-3), where L is bis(2
      benzimidazolylmethyl)amine and B is 1,10-phenanthroline (phen), dipyrido[3,2
      d:2',3'-f]quinoxaline (dpq) or dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been
      prepared, characterized, and their photo-induced DNA and protein cleavage
      activity studied. The photocytotoxicity of complex 3 has been studied using
      adenocarcinoma A549 cells. The phen complex 1, structurally characterized by
      single-crystal X-ray crystallography, shows the presence of a vanadyl group in
      six-coordinate VON(5) coordination geometry. The ligands L and phen display
      tridentate and bidentate N-donor chelating binding modes, respectively. The
      complexes exhibit a d-d band near 740 nm in 15% DMF-Tris-HCl buffer (pH 7.2). The
      phen and dpq complexes display an irreversible cathodic cyclic voltammetric
      response near -0.8 V in 20% DMF-Tris-HCl buffer having 0.1 M KCl as supporting
      electrolyte. The dppz complex 3 exhibits a quasi-reversible voltammogram near 
      0.6 V (vs SCE) that is assignable to the V(IV)-V(III) couple. The complexes bind
      to calf thymus DNA giving binding constant values in the range of 6.6 x 10(4)-2.9
      x 10(5) M(-1). The binding site size, thermal melting and viscosity binding data
      suggest DNA surface and/or groove binding nature of the complexes. The complexes
      show poor "chemical nuclease" activity in dark in the presence of 3
      mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes are
      efficient photocleavers of plasmid DNA in UV-A light of 365 nm via a mechanistic
      pathway that involves formation of both singlet oxygen and hydroxyl radicals. The
      complexes show significant photocleavage of DNA in near-IR light (>750 nm) via
      hydroxyl radical pathway. Among the three complexes, the dppz complex 3 shows
      significant BSA and lysozyme protein cleavage activity in UV-A light of 365 nm
      via hydroxyl radical pathway. The dppz complex 3 also exhibits photocytotoxicity
      in non-small cell lung carcinoma/human lung adenocarcinoma A549 cells giving
      IC(50) value of 17 microM in visible light (IC(50) = 175 microM in dark).

PMID- 20039727
TI  - How electron flow controls contaminant dynamics.

PMID- 20039729
TI  - From hospital to lab: tracing technetium.
AB  - Researchers move a technique from the hospital to the lab to illuminate a
      radioactive element's travels through soil.

PMID- 20039730
TI  - Energetic constraints on H2-dependent terminal electron accepting processes in
      anoxic environments: a review of observations and model approaches.
AB  - Microbially mediated terminal electron accepting processes (TEAPs) to a large
      extent control the fate of redox reactive elements and associated reactions in
      anoxic soils, sediments, and aquifers. This review focuses on thermodynamic
      controls and regulation of H2-dependent TEAPs, case studies illustrating this
      concept, and the quantitative description of thermodynamic controls in modeling.
      Other electron transfer processes are considered where appropriate. The work
      reviewed shows that thermodynamics and microbial kinetics are connected near
      thermodynamic equilibrium. Free energy thresholds for terminal respiration are
      physiologically based and often near -20 kJ mol(-1), depending on the mechanism
      of ATP generation; more positive free energy values have been reported under
      "starvation conditions" for methanogenesis and lower values for TEAPs that
      provide more energy. H2-dependent methanogenesis and sulfate reduction are under
      direct thermodynamic control in soils and sediments and generally approach
      theoretical minimum energy thresholds. If H2 concentrations are lowered by
      thermodynamically more potent TEAPs, these processes are inhibited. This
      principle is also valid for TEAPS providing more free energy, such as
      denitrification and arsenate reduction, but electron donor concentration cannot
      be lowered so that the processes reach theoretical energy thresholds.
      Thermodynamics and kinetics have been integrated by combining traditional
      descriptions of microbial kinetics with the equilibrium constant K and reaction
      quotient Q of a process, taking into account process-specific threshold energies.
      This approach is dynamically evolving toward a general concept of microbially
      driven electron transfer in anoxic environments and has been used successfully in
      applications ranging from bioreactor regulation to groundwater and sediment
      biogeochemistry.

PMID- 20039731
TI  - Hydrous manganese oxide doped gel probe sampler for measuring in situ reductive
      dissolution rates. 1. Laboratory development.
AB  - Reductive dissolution of redox-sensitive minerals such as manganese (Mn) oxides
      in natural sediments is an important mechanism for trace element mobilization
      into groundwater. A gel probe sampler has been constructed to study in situ
      reductive dissolution of Mn oxides. The gel consists of a polyacrylamide polymer
      matrix doped with hydrous Mn oxide (HMO). Gel slabs are mounted into a probe,
      which is designed to be inserted into the sediments. The amount of Mn released
      from the gel by reductive dissolution is determined by comparing the amount of Mn
      initially embedded into the gel with the amount remaining in the gel after
      exposure to conditions in the sediments or, in laboratory studies, to reducing
      agents. In this laboratory study, the performance of the gel probes was examined
      using the model reductant ascorbate and the Mn-reducing bacteria Shewanella
      oneidensis strain MR-1. In addition, a 1-D model was used to relate the reaction
      rates observed for HMO embedded in gels to those for HMO in suspension. One
      limitation of the HMO-doped gels for assessing microbial reduction rates is that
      the gels prevent direct contact between the microbes and the HMO and hence
      preclude enzymatic reduction at the cell surface. Nonetheless, the HMO-doped gel
      probes offer the possibility to establish a lower bound for Mn-reduction capacity
      in sediments.

PMID- 20039732
TI  - Hydrous manganese oxide doped gel probe sampler for measuring in situ reductive
      dissolution rates. 2. Field deployment.
AB  - In situ rates of reductive dissolution in submerged shoreline sediments at Lake
      Tegel (Berlin, Germany) were measured with a novel hydrous manganese (Mn) oxide
      doped gel probe sampler in concert with equilibrium gel probe and sequential
      extraction measurements. Rates were low in the top 8 cm, then showed a peak from
      8 to 14 cm, with a maximum at 12 cm depth. This rate corresponded with a peak in
      dissolved porewater iron (Fe) at 11 cm depth. Below 14 cm, the reductive
      dissolution rate reached an intermediate steady value. Lower rates at depth
      corresponded with increases in operationally defined fractions of carbonate-bound
      and organic- and sulfide-bound Mn and Fe as detected by sequential extraction.
      Observed rates of reductive dissolution, which reflect a capacity for Mn
      reduction rather than actual rates under ambient conditions, appear to correlate
      with porewater chemistry and sequential extraction fractions as expected in early
      sediment diagenesis, and are consistent with previous measurements of in situ
      reductive dissolution rates. Significant downward advection in this bank
      filtration setting depletes the Mn and Fe oxides in the sediments and enhances
      the transport of dissolved Fe and Mn into the infiltrating water.

PMID- 20039733
TI  - Redox behavior of magnetite: implications for contaminant reduction.
AB  - The factors controlling rates of contaminant reduction by magnetite (Fe3O4) are
      poorly understood. Here, we measured the reduction rates of three ArNO2 compounds
      by magnetite particles ranging from highly oxidized (x = Fe2+/Fe3+ = 0.31) to
      fully stoichiometric (x = 0.50). Rates of ArNO2 reduction became almost 5 orders
      of magnitude faster as the particle stoichiometry increased from x = 0.31 to
      0.50. To evaluate what was controlling the rate of ArNO2 reduction, we measured
      apparent 15N kinetic isotope effects ((15)N-AKIE) values for nitrobenzene and
      magnetite open-circuit potentials (E(OCP)). 15N-AKIE values were greater than
      unity for all magnetite stoichiometries investigated, indicating that mass
      transfer processes are not controlling the rate of ArNO2 reduction by magnetite.
      E(OCP) measurements showed that the E(OCP) for magnetite was linearly related to
      the stoichiometry, with more stoichiometric magnetite having a lower potential.
      Based on these results, we propose that conceptual models that incorporate both
      redox and Fe2+ diffusion processes, rather than those that rely solely on
      diffusion of Fe2+, are more appropriate for understanding contaminant reduction
      by magnetite. Our work indicates that particle stoichiometry should be considered
      when evaluating rates of contaminant reduction by magnetite.

PMID- 20039734
TI  - Connecting observations of hematite (alpha-Fe2O3) growth catalyzed by Fe(II).
AB  - Electron exchange between aqueous Fe(II) and structural Fe(III) in iron oxides
      and oxyhydroxides is important for understanding degradation of environmental
      pollutants through its apparent constitutive role underlying highly reactive
      "sorbed Fe(II)" and by catalyzing phase interconversion among these minerals.
      Although a mechanistic understanding of relationships between interfacial
      Fe(II)(ads)-Fe(III)(oxide) electron transfer, bulk electron conduction, Fe(II)
      release, and phase transformation behavior is emerging, much remains unclear, in
      part due to poorly interconnected investigations. The focus of this study is on
      reconciling two mutually similar observations of Fe(II)-catalyzed hematite growth
      documented spectroscopically and microscopically under substantially different
      chemical conditions. Here, we employ iron isotopic labeling to demonstrate that
      hematite grown on the (001) surface in Fe(II)-oxalate solution at pH 2.10 and 348
      K has magnetic properties that closely correspond to those of hematite grown in
      Fe(II) solution at pH 7.4 and room temperature. The temperature evolution and
      extent of the Morin transition displayed in these two materials strongly suggest
      a mechanistic link involving trace structural Fe(II) incorporation into the
      growing hematite. Our findings indicate that Fe(II) catalyzed growth of hematite
      on hematite can occur under environmentally relevant conditions and may be due to
      bulk electron conduction previously demonstrated for hematite single crystals.

PMID- 20039735
TI  - Outer membrane-associated serine protease involved in adhesion of Shewanella
      oneidensis to Fe(III) oxides.
AB  - The facultative anaerobe Shewanella oneidensis MR-1 respires a variety of
      anaerobic electron acceptors, including insoluble Fe(III) oxides. S. oneidensis
      employs a number of novel strategies for respiration of insoluble Fe(III) oxides,
      including localization of respiratory proteins to the cell outer membrane (OM).
      The molecular mechanism by which S. oneidensis adheres to and respires Fe(III)
      oxides, however, remains poorly understood. In the present study, whole cell
      fractionation and MALDI-TOF-MS/MS techniques were combined to identify a serine
      protease (SO3800) associated with the S. oneidensis OM. SO3800 contained
      predicted structural motifs similar to cell surface-associated serine proteases
      that function as bacterial adhesins in other gram-negative bacteria. The gene
      encoding SO3800 was deleted from the S. oneidensis genome, and the resulting
      mutant strain (DeltaSO3800) was tested for its ability to adhere to and respire
      Fe(III) oxides. DeltaSO3800 was severely impaired in its ability to adhere to
      Fe(III) oxides, yet retained wild-type Fe(III) respiratory capability. Laser
      Doppler velocimetry and cryoetch high-resolution SEM experiments indicated that
      DeltaSO3800 displayed a lower cell surface charge and higher amount of surface
      associated exopolysaccharides. Results of this study indicate that S. oneidensis
      may respire insoluble Fe(III) oxides at a distance, negating the requirement for
      attachment prior to electron transfer.

PMID- 20039736
TI  - Spatial patterns and modeling of reductive ferrihydrite transformation observed
      in artificial soil aggregates.
AB  - Within soils, biogeochemical processes controlling elemental cycling are
      heterogeneously distributed owing, in large part, to the physical complexity of
      the media. Here we quantify how diffusive mass-transfer limitation at the soil
      aggregate scale controls the biogeochemical processes governing ferrihydrite
      reductive dissolution and secondary iron mineral formation. Artificial cm-scale
      aggregates made of ferrihydrite-coated sand inoculated with iron-reducing
      bacteria were placed in flow-through reactors, mimicking macro- and microporous
      soil environments. A reactive transport model was developed to delineate
      diffusively and advectively controlled regions, identify reaction zones and
      estimate kinetic parameters. Simulated iron (Fe) breakthrough-curves show good
      agreement with experimental results for a wide-range of flow rates and input
      lactate concentrations, with only a limited amount (< or =12%) of Fe lost in the
      reactor outflow over a 31 day period. Model simulations show substantial intra
      aggregate, mm-scale radial variations in the secondary iron phase distributions,
      reproducing the trends observed experimentally where only limited transformation
      of ferrihydrite was found near the aggregate surface, whereas extensive formation
      of goethite/lepidocrocite and minor amounts of magnetite and/or siderite were
      observed toward the aggregate center. Our study highlights the important control
      of variations in transport intensities on microbially induced iron transformation
      at the soil aggregate scale.

PMID- 20039737
TI  - Effects of short-term drying and irrigation on electron flow in mesocosms of a
      northern bog and an alpine fen.
AB  - Methane emissions and element mobility in wetlands are controlled by soil
      moisture and redox conditions. We manipulated soil moisture by weekly drying and
      irrigation of mesocosms of peat from a bog and iron and sulfur rich fen. Water
      table changed more strongly in the decomposed fen peat ( approximately 11 cm)
      than in the fibric bog peat ( approximately 5 cm), where impacts on redox
      processes were larger due to larger change in air filled porosity. Methanogenesis
      was partly decoupled from acetogenesis and acetate accumulated up to 5.6 mmol L(
      1) in the fen peat after sulfate was depleted. Irrigation and drying led to rapid
      redox-cycles with sulfate, hydrogen sulfide, nitrate, and methane being produced
      and consumed on the scale of days, contributing substantially to the total
      electron flow and suggesting short-term resilience of the microbial community to
      intermittent aeration. Anaerobic CO2 production was partly balanced by
      methanogenesis (0-34%), acetate fermentation (0-86%), and sulfate reduction (1
      30%) in the bog peat. In the fen peat unknown electron acceptors and
      aerenchymatic oxygen influx apparently drove respiration. The results suggest
      that regular rainfall and subsequent drying may lead to local oxidation-reduction
      cycles that substantially influence electron flow in electron acceptor poor
      wetlands.

PMID- 20039738
TI  - Anaerobic Fe(II)-oxidizing bacteria show as resistance and immobilize as during
      Fe(III) mineral precipitation.
AB  - More than 100 million individuals worldwide are exposed to arsenic-contaminated
      water, making the investigation of arsenic mobility in aquatic systems of utmost
      importance. Iron (hydr)oxides play a key role in preventing arsenic release in
      aquifers and soils due to their strong arsenic sorption and are even used to
      remove arsenic in water treatment. Neutrophilic Fe(II)-oxidizing bacteria produce
      Fe(III) minerals and therefore have the potential to affect arsenic mobility. In
      the present study, we demonstrate that the metabolism of anaerobic nitrate
      reducing and phototrophic Fe(II)-oxidizing bacteria is not significantly affected
      by arsenate concentrations of up to 500 muM (37.5 mg/L). Even in the presence of
      the more toxic arsenic species, arsenite, cell metabolism was significantly
      impaired only at the highest arsenite concentration (500 muM) for one of the
      Fe(II)-oxidizers. All Fe(II)-oxidizing bacteria tested effectively immobilized
      arsenic during Fe(II) oxidation (>96%), lowering the remaining dissolved arsenic
      concentrations to values close to or even lower than the current drinking water
      limit of 10 microg/L. Since the minerals formed by these bacteria included highly
      crystalline Fe(III) minerals that are hardly reducible by Fe(III)-reducing
      bacteria, stimulation of arsenic immobilization by Fe(II)-oxidizing bacteria can
      potentially support water treatment systems or even be applied as an effective
      remediation strategy.

PMID- 20039739
TI  - Redox transformation of arsenic by Fe(II)-activated goethite (alpha-FeOOH).
AB  - The redox state and speciation of the metalloid arsenic (As) determine its
      environmental fate and toxicity. Knowledge about biogeochemical processes
      influencing arsenic redox state is therefore necessary to understand and predict
      its environmental behavior. Here we quantified arsenic redox changes by pH
      neutral goethite [alpha-Fe(III)OOH] mineral suspensions amended with Fe(II) using
      wet-chemical and synchrotron X-ray absorption (XANES) analysis. Goethite itself
      did not oxidize As(III) and, in contrast to thermodynamic predictions, Fe(II)
      goethite systems did not reduce As(V). However, we observed rapid oxidation of
      As(III) to As(V) in Fe(II)-goethite systems. Mossbauer spectroscopy showed
      initial formation of (57)Fe-goethite after (57)Fe(II) addition plus a so far
      unidentified additional Fe(II) phase. No other Fe(III) phase could be detected by
      Mossbauer, EXAFS, SEM, XRD, or HR-TEM. This suggests that reactive Fe(III)
      species form as an intermediate Fe(III) phase upon Fe(II) addition and electron
      transfer into bulk goethite but before crystallization of the newly formed
      Fe(III) as goethite. In summary this study indicates that in the simultaneous
      presence of Fe(III) oxyhydroxides and Fe(II), as commonly observed in
      environments inhabited by iron-reducing microorganisms, As(III) oxidation can
      occur. This potentially explains the presence of As(V) in reduced groundwater
      aquifers.

PMID- 20039740
TI  - Evidence for different surface speciation of arsenite and arsenate on green rust:
      an EXAFS and XANES study.
AB  - The knowledge of arsenic speciation at the surface of green rusts (GRs),
      [Fe(II)((1-x))Fe(III)(x) (OH)(2)](x+) (CO(3), Cl, SO(4))(x-), is environmentally
      relevant because arsenic sorption onto GRs could contribute to arsenic retention
      in anoxic environments (hydromorphic soils, marine sediments, etc.). The nature
      of arsenic adsorption complexes on hydroxychloride green rust 1 (GR1Cl) at near
      neutral pH under anoxic conditions was investigated using extended X-ray
      absorption fine structure (EXAFS) spectroscopy at the As K-edge. Sorption data
      indicate that As(V) sorbs more efficiently than As(III) at the studied As
      loadings (0.27 micromol m(-2) and 2.7 micromol m(-2)). EXAFS results indicate
      that arsenite [As(III)] and arsenate [As(V)] form inner-sphere complexes on the
      surface of GR1Cl at arsenic surface coverages of 0.27 and 2.70 micromol m(-2),
      with distinct types of As(III) and As(V) sorption complexes, which change in
      relative concentration as a function of arsenic loading. For As(V), the EXAFS
      derived As-Fe distances (3.34 +/- 0.02 and 3.49 +/- 0.02 A) suggest the presence
      of binuclear bidentate double-corner complexes ((2)C) and monodentate mononuclear
      corner-sharing complexes ((1)V). For As(III), EXAFS-derived As-As distance (3.32
      +/- 0.02 A) and As-Fe distances (3.49 +/- 0.02 and 4.72 +/- 0.02 A) are
      consistent with the presence of dimers of As(III) pyramids binding to the edges
      of the GR1Cl layers by corner sharing with FeO(6) octahedra. However, (2)C and
      (1)V As(III) complexes cannot be excluded. These results improve our knowledge of
      the mode of As(V) and As(III) inner-sphere adsorption on green rusts, which will
      help to constrain sorption modeling of arsenic in soils, sediments, and aquifers.

PMID- 20039741
TI  - Temperature dependence and coupling of iron and arsenic reduction and release
      during flooding of a contaminated soil.
AB  - Arsenic (As) in soils and sediments is commonly mobilized when anoxic conditions
      promote microbial iron (Fe) and As reduction. Recent laboratory studies and field
      observations have suggested a decoupling between Fe and As reduction and release,
      but the links between these processes are still not well understood. In microcosm
      experiments, we monitored the formation of Fe(II) and As(III) in the porewater
      and in the soil solid-phase during flooding of a contaminated floodplain soil at
      temperatures of 23, 14, and 5 degrees C. At all temperatures, flooding induced
      the development of anoxic conditions and caused increasing concentrations of
      dissolved Fe(II) and As(III). Decreasing the temperature from 23 to 14 and 5
      degrees C strongly slowed down soil reduction and Fe and As release. Speciation
      of As in the soil solid-phase by X-ray absorption spectroscopy (XAS) and
      extraction of the Fe(II) that has formed by reductive Fe(III) (hydr)oxide
      dissolution revealed that less than 3.9% of all As(III) and less than 3.2% of all
      Fe(II) formed during 52 days of flooding at 23 degrees C were released into the
      porewater, although 91% of the initially ascorbate-extractable Fe and 66% of the
      total As were reduced. The amount of total As(III) formed during soil reduction
      was linearly correlated to the amount of total Fe(II) formed, indicating that the
      rate of As(V) reduction was controlled by the rate of microbial Fe(III)
      (hydr)oxide reduction.

PMID- 20039742
TI  - Dissolved organic matter sources and consequences for iron and arsenic
      mobilization in Bangladesh aquifers.
AB  - Iron (Fe) and dissolved organic matter (DOM) cycling have been implicated in
      arsenic mobilization via microbially mediated Fe oxide reduction. To evaluate the
      sources and multiple roles of DOM in Bangladesh aquifers, we conducted
      spectroscopic analyses on various types of surface water and groundwater samples
      from a site representative of aquifer chemistry and hydrology. Surface water
      contained humic substances with oxidized quinone-like moieties and high
      concentrations of labile microbially derived DOM. In contrast, in shallow
      groundwater where dissolved iron and arsenic concentrations were high, the
      quinone-like moieties of humic substances were more reduced, with less abundant
      labile DOM than that of surface water. Instead, DOM at these depths was
      characterized by terrestrial (plant/soil) signatures. A sediment microcosm
      experiment demonstrated that Fe(II) and terrestrially derived DOM were released
      from sediment over time. The results provide new evidence to support a dual role
      of natural DOM in Bangladesh aquifers (1) as a labile substrate for Fe- and humic
      reducing bacteria and (2) as an electron shuttle via humic substances to enhance
      microbial iron reduction. Fluorescence index, amino acid-like fluorescence, and
      redox index may serve as useful indicators of the type of DOM likely to be
      involved in Fe solubilization and potentially As mobilization reactions.

PMID- 20039743
TI  - Microfungal alkylation and volatilization of selenium adsorbed by goethite.
AB  - Selenium adsorbed in the oxyanionic form by Fe-oxides like goethite is considered
      of benefit for long-term stabilization of (79)Se under near field conditions of
      radionuclide waste disposal sites. However, microbe-mediated volatilization of
      the uranium fission product (79)Se has not yet been considered for risk
      assessment based on the use of the water-solid distribution coefficient K(D). We
      have performed incubation experiments in a ternary system selenium-microbe
      goethite and show that mycobiota including the common black microfungi genera
      Alternaria alternata are capable of volatilizing the Se even if immobilized by
      goethite. The microfungi were incubated in a standardized nutrient broth
      suspension with 10 g L(-1) of the oxide target under defined conditions. Volatile
      organic selenium (VOSe) species formed in the head space of the culture flasks
      were sampled and measured directly by a cryotrapping cryofocusing gas
      chromatographic system coupled with ICP-MS detection (CT-CF-GC-ICP-MS). Alkylated
      VOSe species were found at the tens to hundreds ng m(-3) levels dominated by
      dimethyl selenide (DMSe) and dimethyl diselenide (DMDSe). The total amount of
      DMSe released into the 80-mL headspace volume within the 21 days of incubation
      was up to 1.12 +/- 0.17 nmol and 0.48 +/- 0.12 nmol for systems without and with
      goethite amendment, respectively. Alkylation rates of up to 0.1 mumol Se per day
      and g biomass cannot be neglected as a potential fission product mobilization
      pathway, unless the inherent radioactivity is proven to prevent any such
      microbial activity on the long-term. Otherwise it may lead to an onsite
      accumulation of (79)Se through evapoconcentration in the enclosed underground
      caverns.

PMID- 20039744
TI  - Rates of hexavalent chromium reduction in anoxic estuarine sediments: pH effects
      and the role of acid volatile sulfides.
AB  - Rates of Cr(VI) reduction were assessed in batch kinetic experiments using dilute
      suspensions of anoxic sediments collected from the Baltimore Harbor. Rapid and
      complete Cr(VI) reduction occurred on the time scale of minutes (pseudo-first
      order rate constants ranged from 0.01 to 0.40 min(-1) for 1.0 g/L sediment
      suspensions at pH 7.0) via reaction with mineral surfaces. The reaction rate was
      first-order with respect to Cr(VI) concentration and proportional to the
      concentration of sediment acid volatile sulfides (AVS). AVS-normalized rates of
      Cr(VI) reduction decreased by approximately 2 orders of magnitude as the
      suspension pH increased from 5.0 to 8.2. The AVS-normalized rate constant was
      linearly correlated with the fraction of total dissolved Cr(VI) in the protonated
      HCrO(4)(-) form at a given pH (f(HCrO(4))((-))). The following rate law was found
      to describe all the experimental data: d[Cr(VI)]/dt = -k[AVS]f(HCrO(4))((
      ))[Cr(VI)](T), where the AVS- and pH-independent rate constant k = 3.14(+/-0.75)
      x 10(4) M(-1) min(-1). The results of this study suggest the importance of
      reactions between Cr(VI) and solid phase AVS constituents in controlling Cr(VI)
      fate in anoxic estuarine sediments, and indicate that Cr(VI) is unlikely to be a
      toxicological stressor in AVS-containing sediments.

PMID- 20039745
TI  - Role of nitrate in conditioning aquifer sediments for technetium bioreduction.
AB  - Here we examine the bioreduction of technetium-99 in sediment microcosm
      experiments with varying nitrate and carbonate concentrations added to synthetic
      groundwater to assess the influence of pH and nitrate on bioreduction processes.
      The systems studied include unamended-, carbonate buffered-, low nitrate-, and
      high nitrate-groundwaters. During anaerobic incubation, terminal electron
      accepting processes (TEAPs) in the circumneutral pH, carbonate buffered system
      progressed to sulfate reduction, and Tc(VII) was removed from solution during
      Fe(III) reduction. In the high-nitrate system, pH increased during
      denitrification (pH 5.5 to 7.2), then TEAPs progressed to sulfate reduction.
      Again, Tc(VII) removal was associated with Fe(III) reduction. In both systems,
      XAS confirmed reduction to hydrous Tc(IV)O(2) like phases on Tc removal from
      solution. In the unamended and low-nitrate systems, the pH remained low, Fe(III)
      reduction was inhibited, and Tc(VII) remained in solution. Thus, nitrate can have
      complex influences on the development of the metal reducing conditions required
      for radionuclide treatment. High nitrate concentrations stimulated
      denitrification and caused pH neutralization facilitating Fe(III) reduction and
      Tc(VII) removal; acidic, low nitrate systems showed no Fe(III)-reduction. These
      results have implications for Tc-cycling in contaminated environments where
      nitrate has been considered undesirable, but where it may enhance Fe(III)
      reduction via a novel pH "conditioning" step.

PMID- 20039746
TI  - Probing the biogeochemical behavior of technetium using a novel nuclear imaging
      approach.
AB  - Dynamic gamma-camera imaging of radiotracer technetium ((99m)Tc) was used to
      assess the impact of biostimulation of metal-reducing bacteria on technetium
      mobility at 10(-12) mol L(-1) concentrations in sediments. Addition of the
      electron donor acetate was used to stimulate a redox profile in sediment columns,
      from oxic to Fe(III)-reducing conditions. When (99m)Tc was pumped through the
      columns, real-time gamma-camera imaging combined with geochemical analyses showed
      technetium was localized in regions containing biogenic Fe(II). In parallel
      experiments, electron microscopy with energy-dispersive X-ray (EDX) mapping
      confirmed sediment-bound Tc was associated with iron, while X-ray absorption
      spectroscopy (XAS) confirmed reduction of Tc(VII) to poorly soluble Tc(IV).
      Molecular analyses of microbial communities in these experiments supported a
      direct link between biogenic Fe(II) accumulation and Tc(VII) reductive
      precipitation, with Fe(III)-reducing bacteria more abundant in technetium
      immobilization zones. This offers a novel approach to assessing radionuclide
      mobility at ultratrace concentrations in real-time biogeochemical experiments,
      and confirms the effectiveness of biostimulation of Fe(III)-reducing bacteria in
      immobilizing technetium.

PMID- 20039747
TI  - Kinetic and mechanistic constraints on the oxidation of biogenic uraninite by
      ferrihydrite.
AB  - The oxidation state of uranium plays a major role in determining uranium mobility
      in the environment. Under anaerobic conditions, common metal respiring bacteria
      enzymatically reduce soluble U(VI) to U(IV), resulting in the formation of
      sparingly soluble UO(2(bio)) (biogenic uraninite). The stability of biologically
      precipitated uraninite is critical for determining the long-term fate of uranium
      and is not well characterized within soils and sediments. Here, we demonstrate
      that biogenic uraninite oxidation by ferrihydrite, an environmentally ubiquitous,
      disordered Fe(III) (hydr)oxide, appears to proceed through a soluble U(IV)
      intermediate and results in the concomitant production of Fe(II) and dissolved
      U(VI). Uraninite oxidation rates are accelerated under conditions that increase
      its solubility and decrease uraninite surface passivation, which include high
      bicarbonate concentration and pH values deviating from neutrality. Thus, our
      results demonstrate that UO(2(bio)) oxidation by Fe(III) (hydr)oxides is
      controlled by the rate of uraninite dissolution and that this process may limit
      uranium(IV) sequestration in the presence of Fe(III) (hydr)oxides.

PMID- 20039748
TI  - Influence of dynamical conditions on the reduction of U(VI) at the magnetite
      solution interface.
AB  - The heterogeneous reduction of U(VI) to U(IV) by ferrous iron is believed to be a
      key process influencing the fate and transport of U in the environment. The
      reactivity of both sorbed and structural Fe(II) has been studied for numerous
      substrates, including magnetite. Published results from U(VI)-magnetite
      experiments have been variable, ranging from no reduction to clear evidence for
      the formation of U(IV). In this contribution, we used XAS and high resolution (+/
      cryogenic) XPS to study the interaction of U(VI) with nanoparticulate magnetite.
      The results indicated that U(VI) was partially reduced to U(V) with no evidence
      of U(IV). However, thermodynamic calculations indicated that U phases with
      average oxidation states below (V) should have been stable, indicating that the
      system was not in redox equilibrium. A reaction pathway that involves
      incorporation and stabilization of U(V) and U(VI) into secondary phases is
      invoked to explain the observations. The results suggest an important and
      previously unappreciated role of U(V) in the fate and transport of uranium in the
      environment.

PMID- 20039749
TI  - Superoxide decay kinetics in the southern ocean.
AB  - Measurements of superoxide (O(2)(-)) reaction kinetics were made during a
      transect with the research icebreaker Polarstern (ANT24-3) in the Antarctic
      through the Drake Passage in austral autumn 2008. Our sampling strategy was
      designed to investigate the sinks of superoxide in Polar waters; principally
      through reactions with dissolved organic matter (DOM) or metals (copper and
      iron). We modified an existing chemiluminescence flow injection system using
      methyl Cypridina luciferin analog (MCLA) for the detection of O(2)(-) and added
      O(2)(-) using KO(2) as the source. Our results indicate that O(2)(-) in ambient
      seawater had a half-life ranging from 9.3 to 194 s. DTPA additions to seawater,
      to remove the effects of reactions with metals, revealed O(2)(-) decay rates
      consistent with a second order reaction, indicating that the dismutation reaction
      dominated and that reactions with DOM were not significant. Titrations of
      seawater by the addition of nanomolar amounts of iron or copper revealed the
      importance of organic chelation of Fe and/or Cu in controlling the reactivity
      with O(2)(-). Throughout the water column reactions with Cu appeared to be the
      major sink for superoxide in the Southern Ocean. This new strategy suggests an
      alternative approach for speciation measurements of Fe and Cu in seawater.

PMID- 20039750
TI  - Exposures to particulate air pollution and nitro-polycyclic aromatic hydrocarbons
      among taxi drivers in Shenyang, China.
AB  - Exposures to particulate matter (PM) of both 10-2.5 microm (PM(10-2.5)) and below
      2.5 microm (PM(2.5)) were measured for a cohort of taxi drivers in Shenyang,
      China, during August 2007. PM samples were collected inside and outside the taxi
      during the drivers' workshifts, and also inside the drivers' homes when they were
      off-shift. Ambient PM samples were also collected at a stationary location in
      Shenyang. Elemental carbon (EC) and organic carbon (OC) were also measured in PM
      collected on quartz filters inside the taxis as well as at the stationary site.
      Concentrations of three nitro-polycyclic aromatic hydrocarbons (NPAHs), 1
      nitropyrene (1NP), 2-nitropyrene (2NP), and 2-nitrofluoranthene (2NFl), were
      determined in extracts of the PM samples by using a 2D-HPLC-MS/MS method. The 2NP
      and 2NFl concentrations did not change substantially with sampling location, but
      the 1NP concentrations were much higher in samples collected inside and outside
      the taxis as compared with sampling locations that were more removed from
      traffic. Concentration ratios of specific NPAHs were used to assess the
      atmospheric conditions in Shenyang during the sampling period. The relatively
      high ratios of 2NFl/1NP ( approximately 8-50) indicate an important contribution
      from secondary NPAH formation to ambient NPAH levels, especially for the nontaxi
      samples. The ratios of 2NFl/2NP (2.5-4.3) indicate that 2NFl is primarily formed
      via the hydroxyl-initiated reaction.

PMID- 20039751
TI  - Pressure monitoring and characterization of external sources of contamination at
      the site of the payment drinking water epidemiological studies.
AB  - The 1990s epidemiological studies by Payment and colleagues suggested that an
      increase in gastrointestinal illnesses observed in the population consuming tap
      water from a system meeting all water quality regulations might be associated
      with distribution system deficiencies. In the current study, the vulnerability of
      this distribution system to microbial intrusion was assessed by characterizing
      potential sources of contamination near pipelines and monitoring the frequency
      and magnitude of negative pressures. Bacterial indicators of fecal contamination
      were recovered more frequently in the water from flooded air-valve vaults than in
      the soil or water from pipe trenches. The level of fecal contamination in these
      various sources was more similar to levels from river water rather than
      wastewater. Because of its configuration, this distribution system is vulnerable
      to negative pressures when pressure values out of the treatment plant reach or
      drop below 172 kPa (25 psi), which occurred nine times during a monitoring period
      of 17 months. The results from this investigation suggest that this distribution
      system is vulnerable to contamination by intrusion. Comparison of the frequency
      of occurrence of negative pressure events and repair rates with data from other
      distribution systems suggests that the system studied by Payment and colleagues
      is not atypical.

PMID- 20039752
TI  - Operational boundaries for nitrite accumulation in nitrification based on
      minimum/maximum substrate concentrations that include effects of oxygen
      limitation, pH, and free ammonia and free nitrous acid inhibition.
AB  - Recent studies on shortcut biological nitrogen removal (SBNR), which use the
      concept of denitrification from nitrite, have reported the key factors affecting
      nitrite build-up, such as dissolved oxygen (DO) limitation, pH, and free ammonia
      (FA) and free nitrous acid (FNA) inhibition. This study extends the concept of
      the traditional minimum substrate concentration (S(min)) to explain the
      simultaneous effect of those factors. Thus, we introduce the minimum DO
      concentration (DO(min)) and the maximum substrate concentration (S(max)) that are
      needed to support a steady-state biological system. We define all three values as
      the MSC values. The model provides a method to identify good combinations of pH,
      DO, and total ammonium nitrogen (TAN) to support shortcut nitritation. We use MSC
      curves to show that the effect of DO-alone and the effect of DO plus direct pH
      inhibition cannot give strong enough selection against nitrite oxidizing bacteria
      to work in a practical setting. However, adding the FA and FNA effects gives a
      strong selection effect that is accentuated near pH 8. Thus, a generalized
      conclusion is that having pH approximately 8 is favorable in many situations. We
      defined a specific operational boundary to achieve shortcut nitritation coupled
      to anaerobic ammonium oxidation (ANAMMOX), in which the effluent concentrations
      of total nitrite and total ammonium should be approximately equal. Experimental
      results for alkaline and acidic nitrite-accumulating systems match the trends
      from the MSC approach. In particular, acidic systems had to maintain higher total
      ammonium, total nitrite, and DO concentrations. The MSC values are a practical
      tool to define the operational boundaries for selecting ammonium-oxidizing
      bacteria while suppressing nitrite-oxidizing bacteria.

PMID- 20039753
TI  - Remediation of chromium(VI) by a methane-oxidizing bacterium.
AB  - Methane-oxidizing bacteria are ubiquitous in the environment and are globally
      important in oxidizing the potent greenhouse gas methane. It is also well
      recognized that they have wide potential for bioremediation of organic and
      chlorinated organic pollutants, thanks to the wide substrate ranges of the
      methane monooxygenase enzymes that they produce. Here we have demonstrated that
      the well characterized model methanotroph Methylococcus capsulatus (Bath) is able
      to bioremediate chromium(VI) pollution over a wide range of concentrations (1.4
      1000 mg L(-1) of Cr(6+)), thus extending the bioremediation potential of this
      major group of microorganisms to include an important heavy-metal pollutant. The
      chromium(VI) reduction reaction was dependent on the availability of reducing
      equivalents from the growth substrate methane and was partially inhibited by the
      metabolic poison sodium azide. X-ray spectroscopy showed that the cell-associated
      chromium was predominantly in the +3 oxidation state and associated with cell- or
      medium-derived moieties that were most likely phosphate groups. The genome
      sequence of Mc. capsulatus (Bath) suggests at least five candidate genes for the
      chromium(VI) reductase activity in this organism.

PMID- 20039754
TI  - Serial analysis of gene expression in the skeletal muscles of zebrafish fed with
      a methylmercury-contaminated diet.
AB  - Mercury (Hg) is a widespread environmental contaminant and its organic form,
      methylmercury (MeHg), has been known as a potent neurotoxic since the Minamata
      tragedy. In the Amazonian basin, gold mining leads to MeHg biomagnification all
      along the food web, culminating in piscivorous fish, ultimately responsible for
      contamination of human beings through fish consumption. In order to assess the
      biological impact of dietary MeHg on fish at the genome scale, we contaminated
      zebrafish with MeHg-contaminated food for 25 days (13.5 microg of Hg/g of food).
      A serial analysis of gene expression (SAGE) was conducted on the skeletal muscle
      because this tissue does not perform MeHg demethylation, and 19171 SAGE tags were
      sequenced from the control library versus 22 261 from the MeHg-contaminated
      library, corresponding to 5280 different transcripts. Among those identified, 60
      genes appeared up-regulated and 15 down-regulated by more than 2 times. A net
      impact of MeHg was noticed on 14 ribosomal protein genes, indicating a
      perturbation of protein synthesis. Several genes involved in mitochondrial
      metabolism, the electron transport chain, endoplasmic reticulum (ER) function,
      detoxification, and general stress responses were differentially regulated,
      suggesting an onset of oxidative stress and ER stress. Several other genes for
      which expression varied with MeHg contamination could be clustered in various
      compartments of the cell's life, such as lipid metabolism, calcium homeostasis,
      iron metabolism, muscle contraction, and cell cycle regulation. This study
      reveals the effectiveness of the SAGE approach to acquire a better understanding
      of the MeHg global effects. Furthermore, this is the first time that the SAGE was
      used to characterize the effect of a toxicant at the genome scale in an aquatic
      organism.

PMID- 20039755
TI  - Recombinant albumin and transthyretin transport proteins from two gull species
      and human: chlorinated and brominated contaminant binding and thyroid hormones.
AB  - Environmentally relevant concentrations of selected polychlorinated biphenyl
      (PCB) and polybrominated diphenyl ether (PBDE) flame retardant congeners and
      their hydroxylated (OH) and methoxylated (MeO) analogues that can perturb thyroid
      hormone-dependent processes were comparatively examined with respect to
      competitive binding with thyroxine (T(4)) and 3,5,3'-triiodothyronine (T(3))
      thyroid hormones (THs) on recombinant human and gull albumin and transthyretin
      transport proteins. The liver tissue was from glaucous gulls (Larus hyperboreus)
      from Norway and herring gulls (Larus argentatus) from the Great Lakes of North
      America. We isolated, cloned, sequenced, purified, and expressed the cDNA (cDNA)
      of albumin from liver of herring and glaucous gull. Albumin amino acid sequences
      were identical for both gull species. Concentration-dependent, competitive
      binding curves were generated for T(4) and T(3) binding alone and for selected
      substrates using gull and human recombinant albumin (recALB). Human recALB had
      high preference for T(4) relative to T(3), whereas it was reversed for gull
      recALB. Binding assays with recALB and recTTR gull proteins showed that relative
      to 2,2',4,4'-tetrabromoDE (BDE-47) and 2,2',3,4',5,5',6-heptaCB (CB-187) and the
      MeO-substituted (4-MeO-CB187 and 6-MeO-BDE47) analogues, 4-OH-CB187, 6-OH-BDE47,
      and 4'-OH-BDE49 had the greatest binding affinity and potency, and that
      competitive binding was greater for T(3) relative to T(4). These results indicate
      that xenobiotic ligand binding to human ALB or TTR cannot be used as a surrogate
      for gull binding interactions. The combination of TH-like brominated diphenyl
      ether backbone (relative to the chlorinated biphenyl backbone), and the presence
      of OH-group produced a more effective competitive ligand on human and gull recALB
      and recTTR relative to both T(3) and T(4). This suggests the possibility that OH
      substituted organohalogen contaminants may be an exposure concern to the thyroid
      system in free-ranging gulls as well as for humans.

PMID- 20039757
TI  - Referencing strategy for the direct comparison of nuclear magnetic resonance and
      molecular dynamics motional parameters in RNA.
AB  - Nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD)
      simulations are both techniques that can be used to characterize the structural
      dynamics of biomolecules and their underlying time scales. Comparison of
      relaxation parameters obtained through each methodology allows for cross
      validation of techniques and for complementarity in the analysis of dynamics.
      Here we present a combined NMR/MD study of the dynamics of HIV-1 transactivation
      response (TAR) RNA. We compute relaxation constants (R(1), R(2), and NOE) and
      model-free parameters (S(2) and tau) from a 65 ns molecular dynamics (MD)
      trajectory and compare them with the respective parameters measured in a domain
      elongation NMR experiment. Using the elongated domain as the frame of reference
      for all computed parameters allows for a direct comparison between experiment and
      simulation. We see good agreement for many parameters and gain further insight
      into the nature of the local and global dynamics of TAR, which are found to be
      quite complex, spanning multiple time scales. For the few cases where agreement
      is poor, comparison of the dynamical parameters provides insight into the limits
      of each technique. We suggest a frequency-matching procedure that yields an upper
      bound for the time scale of dynamics to which the NMR relaxation experiment is
      sensitive.

PMID- 20039758
TI  - Ag+ and cysteine quantitation based on G-quadruplex-hemin DNAzymes disruption by
      Ag+.
AB  - Some G-quadruplex-hemin complexes are DNAzyme peroxidases that efficiently
      catalyze H(2)O(2)-mediated reactions, such as the oxidation of ABTS (2,2'
      azinobis(3-ethylbenzothiozoline)-6-sulfonic acid) by H(2)O(2). Since Ag(+)
      chelates guanine bases at the binding sites are involved in G-quadruplex
      formation, the presence of Ag(+) may disrupt these structures and inhibit the
      peroxidase activity of G-quadruplex-hemin DNAzymes. On the basis of this
      principle, a highly sensitive and selective Ag(+)-detection method was developed.
      The method allows simple detection of aqueous Ag(+) with a detection limit of 64
      nM and a linear range of 50-3000 nM. Cysteine (Cys) is a strong Ag(+)-binder and
      competes with quadruplex-forming G-rich oligonucleotides for Ag(+)-binding,
      promoting the reformation of G-quadruplexes and increasing their peroxidase
      activity. Therefore, the Ag(+)-sensing system was also developed as a Cys-sensing
      system. This "turn-on" process allowed the detection of Cys at concentrations as
      low as 50 nM using a simple colorimetric technique. The Cys-sensing system could
      also be used for the detection of reduced glutathione (GSH). Neither the Ag(+)
      sensing nor the Cys-sensing systems required labeled oligonucleotides. In
      addition, both gave large changes in absorbance signal that could be observed by
      the naked eye. Thus, a simple visual method for Ag(+)- or Cys-detection was
      developed.

PMID- 20039759
TI  - Concise synthesis of 2, 3-diarylpyrimido[1,2-a]benzimidazole based on
      isoflavones.
AB  - The 2,3-diarylpyrimido[1,2-a]benzimidazole derivatives were prepared by one-step
      cyclocondensation of 2-aminobenzimidazole with isoflavone in methanol. Single
      crystal diffraction analysis was performed for 2-(2-hydroxyl-4-isopropoxy-phenyl)
      3-phenylpyrimido[1,2-a]benzimidazole. The fluorescence properties of the fused 2,
      3-diarylpyrimido[1, 2-a]benzimidazole were evaluated.

PMID- 20039761
TI  - A study of West Nile virus infection in Iranian blood donors.
AB  - BACKGROUND: West Nile virus is a mosquito transmitted virus that can cause
      disease in humans and horses. A majority of people infected with WNV will have no
      symptoms or may only experience mild symptoms, such as headaches. About 20% of
      infected humans develop a flu-like illness characterized by fever; while in the
      elderly and immunocompromised West Nile virus can cause a more serious neurologic
      disease and may be fatal. West Nile virus infection is endemic in the Middle
      East. West Nile virus can also be transmitted by transfusion through infected
      blood components.The objective of this study is to find the West Nile virus-RNA
      incidence and anti-West Nile virus prevalence amongst Iranian blood donors in
      order to determine whether this emerging infection is a possible risk for the
      blood supply in Iran. METHODS: Serum samples from 500 blood donors who donated
      blood at the Tehran Blood Transfusion Center were collected between May and
      October 2005. Serum samples were examined for IgM and IgG antibodies to West Nile
      virus using the ELISA method. The samples were tested for the presence of West
      Nile virus RNA by the real-time RT-polymerase chain reaction assay. All data were
      analyzed statistically using the Chi-Square test. RESULTS: All 500 donors were
      negative for West Nile virus-specific IgM antibody at the time of donation. No
      WNV RNA-positive samples were detected. The percentage of seropositivity of IgG
      antibodies to WNV was 5% at donation. CONCLUSION: No evidence of WNV-specific IgM
      antibody and WNV RNA in blood donor samples was found. In order to increase the
      safety of blood donation, it is essential to continue surveillance of this
      emerging infection in order to protect the blood supply in the future.

PMID- 20039763
TI  - Wound infection incidence in patients with simple and gangrenous or perforated
      appendicitis.
AB  - BACKGROUND: Performing a delayed primary wound closure is often recommended in
      patients with gangrenous or perforated appendicitis who have undergone an
      appendectomy. It can result in increased pain as well as an extended hospital
      stay which, in turn, increases hospital costs. Delayed primary wound closure
      remains controversial. The general policy in our institution is to perform a
      primary wound closure. In this study, we have compared the incidence of wound
      infection in patients with simple appendicitis to those with gangrenous or
      perforated appendicitis whose wounds were primarily closed. METHODS: This is an
      observational study which was carried out on 400 patients with gangrenous or
      perforated (50%) and simple appendicitis (50%). Both groups underwent primary
      wound closure. Patients were followed for wound infection for at least one month
      after surgery. Data including age, sex, operating time, pathologic report and
      wound infection were collected. A comparison between the studied groups was made
      using Student's t-test for continuous variables and 2 test for categorical
      variables. RESULTS: The median age of the patients was 23 years. There were 141
      (35.2%) females and 259 (64.8%) males. The median operating time was 30 minutes.
      Wound infections were observed in 15 patients (3.7%), including 6 cases of simple
      and 9 cases of gangrenous or perforated appendicitis which was not statistically
      significant. CONCLUSION: There was no statistically significant difference in
      wound infection between the simple and gangrenous or perforated appendicitis
      groups.

PMID- 20039762
TI  - A survey of the status of education and research in anaesthesia and intensive
      care medicine at the University Teaching Hospital in Lusaka, Zambia.
AB  - BACKGROUND: Current knowledge of the situation of anaesthesia in developing
      countries is limited. A survey of the status of education and research based on
      hospital records, records of the anaesthesia section, nursing records, personal
      observations as well as personal communication with staff, patients and hospital
      managers was carried out in a 1863-bed university teaching hospital located in
      the capital of a least developed Sub-Saharan African Country. METHODS:
      Classification and evaluation of the data was based on the three aspects of the
      role of university teaching hospitals in Western countries: (I) patient care,
      (II) university teaching and post-graduation training, as well as (III) research
      activities. The section "patient care" was sub-divided into anaesthesia,
      intensive care medicine, emergency medicine, and pain therapy. The Department of
      Anaesthesia at the University Teaching Hospital of Lusaka, Zambia, is organized
      as a subdivision of the surgical department and is not involved in emergency
      medicine or pain therapy. Thirteen out of seventeen operating theatres, one
      recovery room, and a ten bed intensive care unit are serviced by the Department
      of Anaesthesia. RESULTS: Anaesthetic equipment, medical supplies, drugs, and
      consumables are all in limited supply. There are limited statistics on
      perioperative complications and mortality. Anaesthesia at the university teaching
      hospital of a least developed Sub-Saharan African Country is severely short of
      both a workforce and resources. CONCLUSION: We have described strategies which
      may help to reverse this trend, the most important of which is to promote
      anaesthesia as an essential specialty within hospitals in developing countries.

PMID- 20039764
TI  - Trauma research in Iran: a report of the Sina Trauma Data Bank.
AB  - BACKGROUND: Injuries are a major health problem in developing countries.
      Recently, the occurrence of injuries and those related to mortality have
      increased dramatically in Iran. We have conducted this study to report domestic
      research publications in the field of trauma from 2000 to 2006 in Iran. METHODS:
      The contents of 128 biomedical journals were analyzed. Sina Trauma Data Bank
      (STDB) was selected as an indicator of trauma related articles that have been
      published in Iranian biomedical journals. RESULTS: The number of trauma related
      articles in Iran increased during the seven year period (2000 - 2006), but the
      percentage of total publications was not significantly different. The mean number
      of authors per article was 2.7+1.3 (1 to 12) and all first authors were Iranian.
      Females constituted 15.4% (n=156) of first authors. Original articles were the
      most frequently published articles (n=871; 86.2%). Treatment of injuries and
      ensuing complications were the most common topics (42%) followed by war injuries
      (14.1%). Traffic accidents, as the leading cause of trauma death in Iran, were
      investigated in 27 (2.7%) articles. CONCLUSION: According to our results, it
      seems that more attention from researchers and health-policy makers towards
      trauma is necessary in our country. In addition, publishing a journal with the
      main theme of injury and trauma could be an effective means for increasing the
      proportion of trauma related articles.

PMID- 20039765
TI  - Detection of KIT and FLT3 mutations in acute myeloid leukemia with different
      subtypes.
AB  - BACKGROUND: Mutations in KIT and fms-like tyrosine kinase 3 genes lead to
      uncontrolled proliferation of leukemic cells with a poor prognosis. Since, data
      concerning the incidence and associations with patients characteristics vary
      amongst different studies, the aim of the present study is to identify and
      quantify the frequency of mutations in Iranian patients suffering from acute
      myeloid leukemia. METHODS: Internal tandem duplication and D835 mutations in the
      fms-like tyrosine kinase 3 gene of acute myeloid leukemia patients were studied
      through polymerase chain reaction and polymerase chain reaction-RFLP analysis.
      Amplified products for a point mutation in D816 for KIT have also been identified
      through the polymerase chain reaction-RFLP technique. The mutations in exon 8 of
      KIT were detected by using the PCR and the Conformational Sensitive Gel
      Electrophoresis techniques, and amplified products have been confirmed by
      sequencing techniques. RESULTS: Internal tandem duplication and D835 mutations in
      the fms-like tyrosine kinase 3 gene occurred in 18% and 6% of AML patients,
      respectively. Frequencies of mutation were 1.4% and 4.7% in exon 8 and D816 of
      the KIT gene in acute myeloid leukemia patients. These results were substantially
      different for various subclasses of French-American-British classification.
      CONCLUSION: This study revealed that approximately 30% of acute myeloid leukemia
      patients have either KIT or fms-like tyrosine kinase 3 genetic mutations. The
      presence of fms-like tyrosine kinase 3 was significantly associated with M3
      morphology and mutations of KIT were significantly associated with M2 and M4
      subtypes.

PMID- 20039767
TI  - Prevalence of anencephaly in Gorgan, northern Iran.
AB  - BACKGROUND: Anencephaly is a neural tube defect incompatible with life. The aim
      of this prospective study was to determine the prevalence of anencephaly in
      Gorgan, northern Iran. METHODS: During 1998 - 2005, 49,534 newborns at Dezyani
      hospital in Gorgan were screened for neural tube defects. Clinical and
      demographic data of the diagnosed cases were recorded in a pre-designed
      questionnaire for analysis. These data included sex, ethnicity, parental
      consanguinity, and residential area. RESULTS: The overall prevalence of neural
      tube defects and anencephaly were 28 and 12 per 10000 births, respectively. The
      prevalence of anencephaly was 11 and 12 per 10000 births in male and female
      newborns, respectively. Considering the parental ethnicity, the prevalence of
      anencephaly was 12, 16, and 7 per 10000 in Fars, Turkman, and Sistani ethnicity,
      respectively. The prevalence of anencephaly was 13.1/10000 in newborns with
      mothers aged >35 years. Consanguinity was seen in 36% of the parents. The highest
      rate of anencephaly occurred in 1999 (23/10000) and the least was in 2003
      (2/10000). The most prevalent season for the occurrence of anencephaly was winter
      (16/10000). CONCLUSION: The present study indicated that the prevalence of
      anencephaly among Iranian newborns in northern Iran was higher than in the
      European population.

PMID- 20039766
TI  - Potent reducing effects of vitamin D3 on the frequency of apoptosis induced by
      arsenic trioxide in NB4 cell line.
AB  - BACKGROUND: Arsenic trioxide and 1,25-(OH)2D3 (vitamin D3) are used for the
      treatment of lymphocytic leukemia. However, the effects of combined treatment of
      these drugs are controversial. In this study, the combined effects of these drugs
      on the induction of apoptosis in NB4 cells were investigated using the neutral
      comet assay. METHODS: NB4 cells were treated with various doses of arsenic
      trioxide (0.1 - 3 microM) and vitamin D3 (100 - 600 nM (alone or in combination.
      Twenty-four hours after treatment, neutral comet assay was performed and
      apoptotic cells were scored under a fluorescent microscope following staining
      with ethidium bromide. RESULTS: Results show that all doses of arsenic trioxide
      used in this study induced apoptosis in NB4 cells. The frequency of induced
      apoptosis was dose dependent and significantly higher than the controls (P<0.05 -
      0.01). In contrast, vitamin D3 at concentrations of 100 - 600 nM produced no
      significant effect on apoptosis induction compared to the controls. Treatment of
      NB4 cells with a combination of arsenic trioxide and vitamin D3 resulted in
      reduction of apoptosis induced by arsenic trioxide which was not dependent on the
      dose of vitamin D3 (P<0.05). CONCLUSION: Results indicate that arsenic trioxide
      is a potent inducer of apoptosis in NB4 cells and vitamin D3 significantly
      decreased the sensitivity of cells to the induction of apoptosis by arsenic
      trioxide. These findings suggest that 1,25-(OH)2D3 might be involved in anti
      apoptotic processes via reactive oxygen species scavenging or other mechanisms
      not yet known.

PMID- 20039768
TI  - A modification of the Brunt system for scoring liver histology of patients with
      non-alcoholic fatty liver disease.
AB  - BACKGROUND: Nonalcoholic steatohepatitis is a common cause of chronic liver
      disease. It is important to have a uniform and validated method for scoring liver
      histology in these patients. Therefore, we propose a modification of the Brunt
      system by scoring the four histologic features separately and reporting their
      sums as the nonalcoholic steatohepatitis activity index. METHODS: A nonalcoholic
      steatohepatitis activity index was defined which scored the grade of disease
      activity between 0 and 12 according to four histologic features: steatosis,
      hepatocyte ballooning, portal inflammation, and lobular inflammation. Fibrosis
      was separately scored between 0 and 4. A total of 60 liver specimens collected
      from nonalcoholic steatohepatitis patients were scored by two pathologists at the
      time of biopsy and after three months. Liver enzyme levels were also correlated
      with the histologic score. RESULTS: The intra-rater agreement (weighted kappa)
      for various variables of the scoring system was between 0.59 and 0.80 for one
      pathologist and 0.78 to 0.95 for the other. The repeatability of the nonalcoholic
      steatohepatitis activity index was excellent with only 4% of the repeated
      measures out of the acceptable range of agreement. In addition, liver enzyme
      levels strongly correlated with the nonalcoholic steatohepatitis activity index.
      CONCLUSION: This system provides a fine graduation of liver histologic damage in
      nonalcoholic steatohepatitis and is well suited for use in clinical trials or
      natural history studies.

PMID- 20039769
TI  - Carpal tunnel syndrome due to lipofibromatous hamartoma of the median nerve.
AB  - This report describes a rare case of secondary carpal tunnel syndrome due to a
      lipofibromatous hamartoma of the median nerve. Excision of the fibrofatty tissue
      between the nerve fascicles without risking damage to the fascicles was
      impossible. The transverse carpal ligament was incised and an epineurotomy was
      performed. Within six months, the 25-year-old female patient's symptoms were much
      improved.

PMID- 20039770
TI  - Extensive focal epithelial hyperplasia.
AB  - Heck's disease or focal epithelial hyperplasia is a benign contagious disease
      caused by human papillomavirus types 13 or 32. It occurs with low frequency in
      the Iranian population. This condition is characterized by the occurrence of
      multiple, small papules or nodules in the oral cavity, especially on the labial
      and buccal mucosa and tongue. In some populations, up to 39% of children are
      affected. Conservative surgical excision of lesions may be performed for
      diagnostic or aesthetic purposes. The risk of recurrence after this therapy is
      minimal, and there seems to be no malignant transformation potential. In the
      present work, we presented the clinical case of a 12-year-old Iranian girl with
      oral lesions that clinically and histologically correspond to Heck's disease.

PMID- 20039771
TI  - Shrapnel splinter in the common bile duct.
AB  - Obstructive jaundice is infrequently caused by a foreign body. We report a 42
      year-old man who presented with obstructive jaundice by an impacted shrapnel
      splinter in the common bile duct (CBD) 23 years after a combat injury. To our
      knowledge, this is the first case report of this type in Iranian literature,
      although there are a few reports of combat related injuries in other countries.
      This diagnosis should be considered in the assessment of any patient with
      jaundice and abdominal pain who has experienced a previous combat injury.

PMID- 20039772
TI  - Photoclinic. Vagus nerve paraganglioma (glomus vagale).

PMID- 20039773
TI  - Asclepius, Caduceus, and Simurgh as medical symbols, part I.
AB  - This is the first of two articles reviewing the history of medical symbols. In
      this first article I have briefly reviewed the evolution of the Greek god,
      Asclepius, (and his Roman counterpart Aesculapius) with the single serpent
      entwined around a wooden rod as a symbol of western medicine and have alluded to
      the misplaced adoption of the Caduceus of the Greek god Hermes (and his Roman
      counterpart Mercury) with its double entwined serpents as an alternative symbol.
      In the second part of this article (to be published later), I have made a
      tentative suggestion of why the Simorgh might be adopted as an Eastern or an
      Asian symbol for medicine.

PMID- 20039774
TI  - A brief history of smallpox eradication in Iran.
AB  - Smallpox, which currently is only of historical interest, was once one of the
      most terrible illnesses with high mortality and morbidity. In the late 18th
      century, the English physician and naturalist, Edward Jenner (1749 - 1823),
      discovered an efficient preventive technique against smallpox which he termed
      "vaccination". Afterwards, the practice of vaccination gradually became
      widespread when finally in 1979, the World Health Organization formally declared
      the global eradication of this fatal disease.Presented here is a brief account of
      smallpox eradication in Iran which started on a limited scale in the 19th century
      by the order of Abbas Mirza (1789 - 1833), the Crown Prince of Fath Ali Shah
      Qajar (reign from 1797 - 1834), and reinforced in 1848 by Mirza Taghi Khan Amir
      Kabir (1807 - 1852) the Prime Minster of Naser ad-Din Shah, and became more
      popular after the establishment of the Pasteur Institute in Tehran in 1921, where
      considerable doses of smallpox vaccine were produced. In addition, in subsequent
      years, a law that mandated public smallpox vaccination was passed by the Iranian
      parliament (Majles) in 1953 and eventually, the mass vaccination program led to
      the complete eradication of smallpox in Iran in 1978.

PMID- 20039775
TI  - Diabetic kidney disease: act now or pay later.

PMID- 20039776
TI  - Opinion article by Habibzadeh and Yadollahie.

PMID- 20039777
TI  - Pharmacokinetic interaction between telithromycin and metformin in diabetes
      mellitus rats.
AB  - Telithromycin and metformin have been reported to be commonly metabolized via
      hepatic CYP3A1/2 in rats. Community-acquired respiratory tract infection was
      reported to be frequent in patients with diabetes mellitus. Compared with
      controls, hepatic CYP3A1/2 was reported to be increased in male rats with
      diabetes mellitus induced by streptozotocin (DMIS rats). After the intravenous
      administration of both drugs together to male DMIS rats, the time-averaged non
      renal clearance (CL(NR)) of metformin was significantly slower (by 33.1%; 10.3
      versus 15.4 ml min(-1) kg(-1)) than metformin alone due to the inhibition of
      hepatic metabolism of metformin by telithromycin via CYP3A1/2. After the oral
      administration of both drugs together, the total area under the plasma
      concentration-time curve (AUC) of metformin was comparable possibly due to the
      increased intestinal metabolism of metformin by telithromycin.

PMID- 20039778
TI  - A new rat model for diffuse axonal injury using a combination of linear
      acceleration and angular acceleration.
AB  - Diffuse axonal injury (DAI) is a frequent form of traumatic brain injury, and is
      usually associated with long-lasting neurological impairments. A new experimental
      model was developed in the present study to induce DAI in rats by combining low
      linear and angular accelerations. In most clinical scenarios, DAI is caused by
      these two forms of acceleration in combination. In the injury-producing facility
      described here, the rat rotated instantly after it had sustained the impact that
      produced linear acceleration. Rats rotated rapidly 90 degrees in the coronal
      plane at a peak angular acceleration of 137 +/- 12 krad/sec(2) with a duration of
      33.7 +/- 1.2 msec. The linear acceleration was applied to the rat's head by
      dropping a 450 g weight from a height of 0.9 m. Rats exposed to the combined
      accelerations took significantly longer to regain consciousness (11.9 +/- 3.6
      min) than control rats (p < 0.01) or rats subjected to purely angular or linear
      acceleration (p < 0.01). Although macroscopic damage was observed in all brain
      injured animals, axonal damage and hemorrhagic tissue tears were only noted in
      the animals sustaining the combined accelerations. All rats survived the purely
      linear or angular acceleration, whereas the mortality rate reached 21.7%
      following the combined accelerations. These results show that this model is
      capable of reproducing the major histological and neurological changes that are
      associated with DAI, and that the combination of low linear and angular
      accelerations can produce non-linear and synergistic effects to induce
      moderate/severe DAI.

PMID- 20039779
TI  - Pharmacokinetics and metabolism of (R,R)-methoxyfenoterol in rat.
AB  - (R,R)-fenoterol (Fen), a beta(2)-adrenoceptor agonist, is under clinical
      investigation in the treatment of congestive heart disease. The pharmacokinetics
      and metabolism of the 4-methoxyphenyl derivative of (R,R)-Fen, (R,R)-MFen, have
      been determined following intravenous and oral administration to the rat and
      compared with corresponding results obtained with (R,R)-Fen. Results from the
      study suggest that (R,R)-MFen can offer pharmacokinetic and metabolic advantages
      in comparison to an earlier (R,R)-Fen. The oral administration revealed that the
      net exposure of (R,R)-MFen was about three-fold higher than that of (R,R)-Fen
      (7.2 versus 2.3 min x nmol ml(-1)), while intravenous administration proved that
      the clearance was significantly reduced, 48 versus 146 ml min(-1) kg(-1), the
      T(1/2) was significantly longer, 152.9 versus 108.9 min, and the area under the
      curve (AUC) was significantly increased, 300 versus 119 min x nmol ml(-1). (R,R)
      MFen was primarily cleared by glucuronidation associated with significant
      presystemic glucuronidation of the compound. After intravenous and oral
      administration of (R,R)-MFen, (R,R)-Fen and (R,R)-Fen-G were detected in the
      urine samples indicating that (R,R)-MFen was O-demethylated and subsequently
      conjugated to (R,R)-Fen-G. The total (R,R)-Fen and (R,R)-Fen-G as a percentage of
      the dose after intravenous administration was 3.6%, while after oral
      administration was 0.3%, indicating that only a small fraction of the drug
      escaped presystemic glucuronidation and was available for O-demethylation. The
      glucuronidation pattern was confirmed by the results from in vitro studies where
      incubation of (R,R)-MFen with rat hepatocytes produced (R,R)-MFen-G, (R,R)-Fen
      and (R,R)-Fen-G, while incubation with rat intestinal microsomes only resulted in
      the formation of (R,R)-MFen-G.

PMID- 20039780
TI  - Cologenital fistula secondary to diverticulitis.

PMID- 20039781
TI  - Cytokine and autoantibody patterns in acute liver failure.
AB  - The mechanisms of idiosyncratic drug-induced liver injury (IDILI) are still a
      matter of dispute. Some of the characteristics of reactions that have been
      classed as metabolic idiosyncrasy could also be those of an immune-mediated
      reaction with an autoimmune component. Many auto-immune reactions appear to be
      mediated by T(H)17 cells, which are in part characterized by the production of
      interleukin (IL)-17. To test the involvement of T(H)17 cells in IDILI, we
      quantified a number of cytokines, chemokines, and autoantibodies in the serum of
      39 patients with acute liver failure (ALF) due to IDILI and compared the values
      with those from 21 patients with acetaminophen-induced ALF and 10 patients with
      viral hepatitis-induced ALF. The IL-17 levels were elevated in 60% of patients
      with IDILI, but also in a similar number of patients with acetaminophen-induced
      ALF and occasionally in patients with viral hepatitis. Levels of other cytokines,
      such as IL-21, that are also produced by T(H)17 cells were higher in patients
      with IDILI, but again, there was overlap with acetaminophen DILI. Autoantibodies
      were more frequent in patients in the IDILI group but were absent in most
      patients. These data provide a picture of the cytokine/chemokine profile in
      patients with various types of ALF. The pattern varies from patient to patient
      and not specifically by etiology. This suggests that different underlying disease
      mechanisms may be at play in different individuals, even among those
      demonstrating injury from the same drug. Since cytokines may originate from more
      than one type of cell, interpretation of results of cytokine assays remains
      difficult in complex disease settings.

PMID- 20039782
TI  - Production of HIV-1 integrase fusion protein-carrying lentiviral vectors for gene
      therapy and protein transduction.
AB  - Lentiviral vectors have broad target cell tropism and efficient machinery to
      integrate transgenes into the host genome. Modification of these vectors by
      incorporating heterologous proteins into virions has relied mostly on the fusion
      of proteins into the HIV-1 accessory protein Vpr. Vpr expression can be harmful
      for cells and its gene has been deleted from third-generation vector production
      plasmids. We therefore developed a direct integrase fusion protein strategy as an
      alternative way to package heterologous proteins into vectors. The method was
      tested by creating two different integrase fusion proteins, IN-p53 and IN
      mCherry, cloned into the 3' end of pol in the packaging plasmid. Lentiviral
      vectors were produced by conventional methods, using the modified packaging
      plasmids. Vector-incorporated fusion proteins were correctly processed from Gag
      Pol, retained the ability to catalyze transgene integration, and showed fusion
      protein-specific activity by being fluorescent or inducing apoptosis. Functional
      third-generation lentiviral vectors containing IN-fusion proteins can thus be
      produced by standard production protocols independent of Vpr expression. Our
      results suggest that this packaging method is useful for lentiviral vector
      mediated protein transduction, such as intranuclear meganuclease, transposon, or
      zinc finger protein delivery, intracellular imaging of vector particles, and
      generation of modified lentiviral vectors that contain both toxic and nontoxic IN
      fusion proteins.

PMID- 20039783
TI  - Pharmacogenetic testing in the United Kingdom genetics and immunogenetics
      laboratories.
AB  - AIM: For certain drugs, pharmacogenetic tests can reduce adverse drug reactions
      and improve treatment efficacy. However, the adoption of pharmacogenetics into
      clinical practice has been relatively slow. One potential barrier is the capacity
      of laboratories to meet the demands of a clinical pharmacogenetic service. We
      aimed to establish the range, capacity to deliver, and demand for germline
      pharmacogenetic testing in the United Kingdom and Ireland, through an e-survey of
      34 molecular genetics and 28 histocompatibility and immunogenetics (H&I)
      laboratories. RESULTS: Thirty-five percent of molecular genetics laboratories and
      54% of H&I laboratories responded to the survey. The majority of H&I laboratories
      (93%) offered pharmacogenetic testing, whereas only one molecular genetics
      laboratory provided a pharmacogenetic service. HLA-B*5701 was most commonly
      tested to identify those at risk of abacavir hypersensitivity among patients with
      HIV. A number of barriers to testing were identified, including lack of clinician
      knowledge and a lack of scientific evidence. All molecular genetics laboratories
      believed that national coordination of clinical pharmacogenetic services was
      required, whereas only 50% of H&I laboratories supported this view. CONCLUSIONS:
      In the United Kingdom, pharmacogenetic testing is currently being predominantly
      provided through H&I laboratories for a limited number of indications. The number
      of laboratories offering pharmacogenetic tests is increasing and is likely to
      continue to increase over the coming years.

PMID- 20039784
TI  - Six new gap junction beta 1 gene mutations and their phenotypic expression in
      Czech patients with Charcot-Marie-Tooth disease.
AB  - X-linked Charcot-Marie-Tooth (CMTX) disease is a hereditary motor and sensory
      neuropathy caused by mutations in the gap junction beta 1 gene (GJB1 codes for
      connexin 32). In this study we report six novel mutations p.Met1Arg, p.Leu9Phe,
      p.Ser17Tyr, p.Val63Phe, p.Val170Ile, and p.Leu212Phe in GJB1 and their phenotypic
      expression. These mutations affect both intracellular and extracellular parts of
      the GJB1 protein. The screened patients had previously excluded the
      duplication/deletion on 17p11.2 and the male-to-male transfer in the pedigree.
      Except p.Val170Ile, all reported mutations segregated with the CMT phenotype in
      the families and caused CMTX1 neuropathy. Mutations were not found in 200 control
      DNA samples. Additionally, we performed in silico analysis of the novel mutations
      with the program PANTHER. The PANTHER scored five mutations, all but p.Val170Ile,
      as likely deleterious and supported the pathogenicity of the found mutations.
      These results provided evidence that these five mutations are causative for
      CMTX1.

PMID- 20039785
TI  - The protein tyrosine phosphatase, non-receptor type 22 R620W polymorphism does
      not confer susceptibility to psoriasis in the genetic homogeneous population of
      Crete.
AB  - Recent whole-genome and candidate-gene association studies in patients with
      psoriasis (PS) have identified a number of single-nucleotide polymorphisms (SNPs)
      that predispose to disease with moderate risk. Predisposition to PS is known to
      be affected by genetic variation in human leukocyte antigen-C as well as other
      non-human leukocyte antigen genes. We recently reported for the first time as a
      PS-associated SNP the signal transducer and activator of transcription-4 (STAT4)
      rs7574865 polymorphism, which is also associated with several autoimmune
      diseases. The aim of this study was to assess whether the functional R620W
      polymorphism of protein tyrosine phosphatase, non-receptor type 22 (PTPN22) gene
      encoding the lymphoid-specific tyrosine phosphatase, which is known to be
      associated with various autoimmune diseases, also confers increased risk for PS
      in the genetic homogeneous population of Crete. A case-control study was
      performed with 173 PS patients consecutively recruited and 348 healthy controls,
      all of them from the island of Crete. We found that the mutated T allele of the
      PTPN22 1858T SNP was more common in control individuals than in patients with PS
      (odds ratio = 0.39, 95% confidence interval = 0.11-1.04, p = 0.09). No
      considerable difference was observed in terms of sex, age of onset, or clinical
      presentation of psoriatic arthritis. Our results provide evidence that the PTPN22
      1858T allele is not a susceptibility factor for PS in the Cretan population.

PMID- 20039787
TI  - Use of dietary supplements and medication among postmenopausal women with
      vasomotor symptoms.
AB  - OBJECTIVES: To assess how postmenopausal women with severe vasomotor symptoms who
      volunteer for an acupuncture trial (ACUFLASH) differ from the general population
      (the Norwegian Women and Cancer study, NOWAC); and to describe the use of dietary
      supplements and medication during trial intervention and follow-up. METHODS:
      Questionnaire data on postmenopausal women regarding demography and use of
      dietary supplements and medication were compared between the ACUFLASH trial
      (baseline, 2006-2007, n = 267) and the NOWAC study (2004-2005, n = 331).
      Additionally, the trial intervention groups, acupuncture and self-care (n = 134)
      or self-care alone (n = 133), were compared regarding supplements and medication
      use. RESULTS: The prevalence of dietary supplement use was higher among women
      with severe vasomotor symptoms (83.9%) than in the population-based sample
      (74.3%), with particularly extensive use of cod liver oil. The prevalence of
      medication use was 46.4% in ACUFLASH and 55.0% in NOWAC. Trial participants
      reported poorer self-reported health, higher education level and tended to be
      former oral contraceptive users and smokers. At trial baseline, 48.5% of the
      acupuncture group and 60.3% of the self-care group used dietary supplements (p >
      0.05), while 48.5% in the acupuncture group and 45.0% in the self-care group used
      medication (p > 0.05). Use of supplements for vasomotor symptoms increased
      significantly in the self-care group at 12 weeks, while it remained unchanged in
      the acupuncture group. Hormone therapy use increased significantly in both groups
      after intervention. CONCLUSION: Postmenopausal women suffering severe vasomotor
      symptoms used more dietary supplements than the general population. They also had
      poorer self-reported health, but their medication use was similar to that of the
      general population. Acupuncture did not influence use of dietary supplements in
      the randomized intervention.

PMID- 20039788
TI  - Comparative study of the ocular irritation potential of various alkyl
      polyglucoside surfactants.
AB  - In the present work, we assessed the relationship between alkyl carbon chain
      length and ocular irritation potentials using the hen's egg test-chorioallantoic
      membrane (HET-CAM) and bovine corneal opacity and permeability (BCOP) assays
      using 5 commercial alkyl polyglucoside surfactants with different compositions of
      alkyl chain lengths (C(6)-C(16)). With HET-CAM, there was a good correlation
      between the proportion of C(10) alkyl polyglucoside and the eye irritation
      potential Q score (r(2) = 0.912, p = .011). There were no significant differences
      between the proportion of C(10) alkyl polyglucoside and corneal opacity in BCOP
      assays; however, there was a relatively high positive correlation between the
      proportion of C(10) alkyl carbon chain lengths and corneal permeability (r(2) =
      0.736, p = .063).

PMID- 20039789
TI  - Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is
      associated with different molecular characteristics of aggrecan and separated in
      time ex vivo.
AB  - Aggrecan is one of the first proteins to be depleted from articular cartilage in
      early osteoarthritis. We investigated the molecular differences between matrix
      metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a
      consequence of their distinct time-dependent degradation profiles. Cartilage
      degradation was induced by cytokine stimulation in bovine articular cartilage
      explants and quantified by a dye-binding assay and immunoassays. The size of
      degradation fragments was analysed by Western blot. Cytokine stimulation resulted
      in the early release of aggrecanase-mediated aggrecan degradation fragments. In
      contrast, MMP-mediated aggrecan degradation began only at day 16 and continued to
      day 21. Western blot analysis showed that glycosylated high-molecular-weight
      (374)ARGSVI fragments appeared at day 7, in contrast to deglycosylated low
      molecular-weight (342)FFGVG fragments which were detected at day 21. Aggrecan
      degradation may be divided into two different pools, a high-molecular-weight
      aggrecanase-mediated pool, and a low-molecular-weight MMP-mediated pool. This may
      have implications for the development of intervention strategies for OA.

PMID- 20039790
TI  - Through the prism darkly: how do others see psychiatrists?
AB  - OBJECTIVE: With changes in healthcare delivery and public expectations of
      psychiatry and psychiatric services changing, we set out to explore how other
      professions and psychiatrists themselves see their roles. In the UK and the USA,
      recent political imperatives have influenced training and roles of psychiatrists.
      We wanted to explore patient and carer perspectives as well. METHODS: We
      conducted two focus groups with patients and carers to explore their views about
      the roles of the psychiatrist. For occupational therapists and social workers, a
      brief questionnaire was placed on their respective professional organization's
      website. Psychiatric trainees and psychiatrists attending different meetings were
      asked to fill in the questionnaire. RESULTS: Patients and carers wanted to be
      more involved in planning their care. In common with other groups, being
      technically competent, being honest, approachable and being a good listener were
      general characteristics of a good psychiatrist. Occupational therapists saw
      psychiatrists as having a unique expertise and ability to provide leadership and
      also having skills in teaching, research, evaluating evidence and being
      respectful of other professions. Social workers would like psychiatrists to look
      beyond the medical model. CONCLUSIONS: In spite of different methods of
      collecting information, common themes emerge in what stakeholders expect from
      psychiatrists. As a profession, we need to respond to this.

PMID- 20039791
TI  - Clozapine and cardiometabolic health in chronic schizophrenia: correlations and
      consequences in a clinical context.
AB  - OBJECTIVE: The aim of this study was to identify the prevalence of metabolic
      syndrome and its putative precursors in a naturalistic study of non-acute
      inpatients at a psychiatric hospital. METHOD: Anthropometric and biochemical data
      collected from the hospital's annual cardiometabolic survey, along with
      information about prescribed medications, were used to assess the prevalence and
      predictors of physical health problems in patients with schizophrenia. RESULTS:
      Of the 167 patients included in the survey, 52.4% met criteria for metabolic
      syndrome. A shorter duration of hospital admission and clozapine use were
      significant predictors of metabolic syndrome. Age, gender, duration of admission
      and clozapine use were all predictors of individual cardiometabolic risk factors.
      CONCLUSIONS: The findings from this naturalistic study reinforce the high
      prevalence of physical health problems in patients with schizophrenia and the
      important influence that psychiatric treatments can have on physical health. The
      impact of clozapine on cardiometabolic health appears to occur early in the
      course of treatment and emphasizes the need for proactive monitoring and
      interventions from the outset of management.

PMID- 20039792
TI  - Western Australia's mental health court liaison service.
AB  - OBJECTIVE: This article describes the Western Australian mental health court
      liaison service. It examines the outcomes that can be measured to assess mental
      health court liaison services and considers Western Australia's service against
      criteria described in the literature. METHOD: The Western Australian mental
      health court liaison service was reviewed against defined criteria. RESULTS:
      Published criteria to measure effectiveness of mental health court liaison are
      helpful. Western Australia's service was developed to be as effective as it could
      be within the parameters in which it operates. CONCLUSIONS: It is important to
      review the efficacy of a service against criteria over which it has control.
      Outcomes that have specific utility for court liaison are discussed.

PMID- 20039786
TI  - DNA interstrand crosslink repair in mammalian cells: step by step.
AB  - Interstrand DNA crosslinks (ICLs) are formed by natural products of metabolism
      and by chemotherapeutic reagents. Work in E. coli identified a two cycle repair
      scheme involving incisions on one strand on either side of the ICL (unhooking)
      producing a gapped intermediate with the incised oligonucleotide attached to the
      intact strand. The gap is filled by recombinational repair or lesion bypass
      synthesis. The remaining monoadduct is then removed by nucleotide excision repair
      (NER). Despite considerable effort, our understanding of each step in mammalian
      cells is still quite limited. In part this reflects the variety of crosslinking
      compounds, each with distinct structural features, used by different
      investigators. Also, multiple repair pathways are involved, variably operative
      during the cell cycle. G(1) phase repair requires functions from NER, although
      the mechanism of recognition has not been determined. Repair can be initiated by
      encounters with the transcriptional apparatus, or a replication fork. In the case
      of the latter, the reconstruction of a replication fork, stalled or broken by
      collision with an ICL, adds to the complexity of the repair process. The
      enzymology of unhooking, the identity of the lesion bypass polymerases required
      to fill the first repair gap, and the functions involved in the second repair
      cycle are all subjects of active inquiry. Here we will review current
      understanding of each step in ICL repair in mammalian cells.

PMID- 20039793
TI  - Attachment, invasion, and translocation of Campylobacter jejuni in pig small
      intestinal epithelial cells.
AB  - Campylobacters are susceptible to environmental conditions such as starvation,
      temperature, and oxidative stress. Species such as Campylobacter jejuni have
      developed a number of mechanisms for responding to these conditions. We conducted
      a study to investigate whether survival of C. jejuni and pathogen-host cell
      interactions such as adherence, invasiveness, and intraepithelial survival in pig
      small-intestinal (PSI) epithelial cells are altered in response to starvation,
      changes in temperature, and atmospheric oxygen concentration. We assessed the
      ability of C. jejuni to translocate across polarized intestinal epithelial cell
      monolayers by measuring transepithelial electrical resistance (TER). Following
      heat stress, we observed loss of C. jejuni culturability but not viability. Heat
      stressed C. jejuni adhered efficiently to pig intestinal epithelial cells, but
      their invasiveness was significantly impaired when compared with unstressed C.
      jejuni. Prolonged exposure to atmospheric oxygen reduced the ability of C. jejuni
      to adhere to intestinal epithelial cells, whereas brief exposure increased
      invasiveness and intraepithelial survival. By comparison, nutrient limitation
      reduced adherence, invasiveness, and intracellular survival of C. jejuni.
      Adherence of C. jejuni strongly affected the pig intestinal epithelium, as
      reflected by a significant decrease in TER of polarized intestinal epithelial
      cells. No correlation between TER and the translocation capacity of C. jejuni was
      observed. Additionally, campylobacters were detected in the basal chamber of a
      functional small-intestinal epithelial cell model at 3 hours post infection,
      without a significant reduction in the TER value, suggesting transcellular
      transport of C. jejuni into the body.

PMID- 20039794
TI  - Escherichia coli isolates from broiler chicken meat, broiler chickens, pork, and
      pigs share phylogroups and antimicrobial resistance with community-dwelling
      humans and patients with urinary tract infection.
AB  - Escherichia coli is the most common cause of urinary tract infection (UTI).
      Phylogroup B2 and D isolates are associated with UTI. It has been proposed that
      E. coli causing UTI could have an animal origin. The objective of this study was
      to investigate the phylogroups and antimicrobial resistance, and their possible
      associations in E. coli isolates from patients with UTI, community-dwelling
      humans, broiler chicken meat, broiler chickens, pork, and pigs in Denmark. A
      total of 964 geographically and temporally matched E. coli isolates from UTI
      patients (n = 102), community-dwelling humans (n = 109), Danish (n = 197) and
      imported broiler chicken meat (n = 86), Danish broiler chickens (n = 138), Danish
      (n = 177) and imported pork (n = 10), and Danish pigs (n = 145) were tested for
      phylogroups (A, B1, B2, D, and nontypeable [NT] isolates) and antimicrobial
      susceptibility. Phylogroup A, B1, B2, D, and NT isolates were detected among all
      groups of isolates except for imported pork isolates. Antimicrobial resistance to
      three (for B2 isolates) or five antimicrobial agents (for A, B1, D, and NT
      isolates) was shared among isolates regardless of origin. Using cluster analysis
      to investigate antimicrobial resistance data, we found that UTI isolates always
      grouped with isolates from meat and/or animals. We detected B2 and D isolates,
      that are associated to UTI, among isolates from broiler chicken meat, broiler
      chickens, pork, and pigs. Although B2 isolates were found in low prevalences in
      animals and meat, these sources could still pose a risk for acquiring
      uropathogenic E. coli. Further, E. coli from animals and meat were very similar
      to UTI isolates with respect to their antimicrobial resistance phenotype. Thus,
      our study provides support for the hypothesis that a food animal and meat
      reservoir might exist for UTI-causing E. coli.

PMID- 20039795
TI  - Virulotyping and antimicrobial resistance typing of Salmonella enterica serovars
      relevant to human health in Europe.
AB  - The combination of virulence gene and antimicrobial resistance gene typing using
      DNA arrays is a recently developed genomics-based approach to bacterial molecular
      epidemiology. We have now applied this technology to 523 Salmonella enterica
      subsp. enterica strains collected from various host sources and public health and
      veterinary institutes across nine European countries. The strain set included the
      five predominant Salmonella serovars isolated in Europe (Enteritidis,
      Typhimurium, Infantis, Virchow, and Hadar). Initially, these strains were
      screened for 10 potential virulence factors (avrA, ssaQ, mgtC, siiD, sopB, gipA,
      sodC1, sopE1, spvC, and bcfC) by polymerase chain reaction. The results indicated
      that only 14 profiles comprising these genes (virulotypes) were observed
      throughout Europe. Moreover, most of these virulotypes were restricted to only
      one (n = 9) or two (n = 4) serovars. The data also indicated that the virulotype
      did not vary significantly with host source or geographical location.
      Subsequently, a representative subset of 77 strains was investigated using a
      microarray designed to detect 102 virulence and 49 resistance determinants. The
      results confirmed and extended the previous observations using the virulo
      polymerase chain reaction screen. Strains belonging to the same serovar grouped
      together, indicating that the broader virulence-associated gene complement
      corresponded with the serovar. There were, however, some differences in the
      virulence gene profiles between strains belonging to an individual serovar. This
      variation occurred primarily within those virulence genes that were prophage
      encoded, in fimbrial clusters or in the virulence plasmid. It seems likely that
      such changes enable Salmonella to adapt to different environmental conditions,
      which might be reflected in serovar-specific ecology. In this strain subset a
      number of resistance genes were detected and were serovar restricted to a varying
      degree. Once again the profiles of those genes encoding resistance were similar
      or the same for each serovar in all hosts and countries investigated.

PMID- 20039796
TI  - Detection and characterization of extended-spectrum beta-lactamase (TEM-52)
      producing Salmonella serotype Infantis from broilers in Japan.
AB  - During 2004 and 2006, multidrug-resistant Salmonella enterica subspecies enterica
      serovar Infantis (Salmonella Infantis) isolates (n = 120) were recovered from
      broiler cecal samples collected from a meat-processing plant, and the isolates
      were examined. The study was conducted to detect and characterize extended
      spectrum beta-lactamase (ESBL)-producing Salmonella Infantis isolates recovered
      from broiler chickens and determine the mechanisms of transfer of the resistance
      traits. Extended-spectrum cephalosporins-resistant Salmonella Infantis isolates
      producing ESBL TEM-52 were detected. The mutant bla(TEM-52) gene and the wild
      type bla(TEM-1) gene that mediated resistance to ampicillin (an extended-spectrum
      penicillin) and cephalothin (a narrow-spectrum cephalosporin) were located on
      approximately 50-kb conjugative plasmids among beta-lactam-resistant (n = 29)
      isolates. The bla(TEM) genes did not cotransfer with aadA1, sul1 (both associated
      with class 1 integrons), tetA, and dfrA5, signifying a chromosomal location of
      these non-beta-lactam resistance-encoding genes. This is the first report
      describing TEM-52-producing S. enterica from food-producing animals in Japan. An
      emergence of TEM-type ESBL is an important concern to public health because this
      readily transferable resistance mechanism threatens the value of the third
      generation cephalosporins and may reduce the clinical utility of this class of
      antibiotics against pathogenic Gram-negative bacteria.

PMID- 20039797
TI  - Robotic partial cystectomy for bladder cancer: a single-institutional pilot
      study.
AB  - OBJECTIVE: Open partial cystectomy has been used as a curative option for select
      group of patients with bladder cancer. In recent years, the da Vinci Surgical
      Robotic System is being increasingly used to perform complex urologic cancer
      surgeries. We report first on a consecutive cohort of patients undergoing robotic
      partial cystectomy (RPC) for bladder cancer. METHODS: Three consecutive patients
      underwent RPC, two with diagnosis of papillary neoplasm of bladder and one with
      urachal adenocarcinoma at our institution from July 2008 to January 2009.
      Perioperative parameters were prospectively collected and analyzed after
      Institutional Review Board approval. RESULTS: All three patients in the study
      were men with a median age of 50 years (range, 24-70 years). The RPC was
      completed transperitoneally in all three patients without the need for open
      conversion. The operative time, estimated blood loss, and time to hospital
      discharge for the three patients undergoing RPC were 185, 135, and 165 minutes;
      25, 20, and 20 mL; and 5, 2, and 2 days, respectively. The percentage change in
      hematocrit after surgery was within 5% in all patients. There were no
      postoperative complications before discharge; however, one patient was readmitted
      and underwent small bowel resection secondary to bowel obstruction. Final
      pathology demonstrated high-grade carcinoma pT2bNxMx and pTaNxMx papillary
      urothelial carcinoma in two patients and invasive adenocarcinoma of the bladder
      pT3aNxMx in the remaining patient. The median follow-up was 6 months (range, 3-10
      months). All three patients were alive with no signs of recurrent or metastatic
      disease on cystoscopic, cytological, or radiological follow-up. CONCLUSIONS: RPC
      is technically feasible using the da Vinci Surgical Robotic System in select
      patients with bladder cancer without disease recurrence in the short term. A
      larger cohort with long-term follow-up is necessary to validate our results.

PMID- 20039798
TI  - Factors affecting blood loss during percutaneous nephrolithotomy using balloon
      dilation in a large contemporary series.
AB  - OBJECTIVE: Renal hemorrhage is a common and worrisome complication of
      percutaneous nephrolithotomy (PNL). We review factors affecting blood loss and
      transfusion requirements in a large contemporary series of patients undergoing
      PNL utilizing balloon dilation. METHODS: We retrospectively reviewed all patients
      undergoing PNL at one institution from July 2000 to January 2008. Demographics,
      stone parameters, perioperative factors, complications, and stone-free rates were
      evaluated. Hemorrhage was estimated using hematocrit and blood transfusion
      requirement. Various factors were assessed for their association with blood loss
      using univariate models. RESULTS: The 225 patients reviewed had a mean stone size
      of 3.5 +/- 1.8 cm (range, 0.6-9.0 cm), with 54 (23.4%) staghorn and 93 (40.3%)
      partial staghorn calculi. One hundred and seventy-five (75.8%), 173 (74.9%), and
      80 (34.6%) had pelvic, lower pole, and upper pole calculi, respectively. Multiple
      access tracts were used in 12 (5.2%) patients, with overall stone-free and
      complication rates of 80.4% and 14.1%. Complications included postoperative fever
      in 15 patients (6.4%), clinically insignificant pleural effusion in 8 patients
      (3.4%), 2 (0.8%) renal artery pseudoaneurysms requiring angioembolization, and 1
      (0.4%) urinoma requiring stent placement. Mean hematocrit decrease was 6.1 +/-
      4.3%, with three (1.3%) patients receiving blood transfusions. On univariate
      analysis no other statistically significant differences were found between
      hematocrit decrease and stone size or location, presence of partial or complete
      staghorn calculi, diabetes, or number of access tracts. CONCLUSIONS: We report a
      comparable stone-free rate and a lower incidence of blood transfusion among
      patients undergoing PNL using balloon dilation.

PMID- 20039799
TI  - Adaptive value and costs of physiological plasticity to soil moisture limitation
      in recombinant inbred lines of Avena barbata.
AB  - Costs are hypothesized to constrain the evolution of adaptive phenotypic
      plasticity, but they have been difficult to quantify because strong selection
      should eliminate costly genotypes from natural populations. However, recent
      studies suggest that crosses between natural populations can recover these
      genotypes. We determined the adaptive value and costs of, as well as the genetic
      variation for, physiological and morphological plasticity to soil water
      limitation in Avena barbata recombinant inbred lines (RILs) created by crossing
      mesic and xeric ecotypes. All traits were plastic, and plasticity in stomatal
      limitation of photosynthesis and photosynthetic rate before and at reproduction
      was adaptive. However, we detected a significant cost of plasticity only for
      stomatal conductance at reproduction, and the mean cost for all traits of A.
      barbata RILs was at least 50% smaller than costs previously estimated using RILs.
      In addition, heritabilities for plasticity were <0.1 and were significant only
      for photosynthesis at reproduction and leaf mass per unit area. Our results
      suggest that costs are less likely to constrain the evolution of adaptive
      plasticity in A. barbata than genetic variation for plasticity.

PMID- 20039800
TI  - Expanding roles of healthcare epidemiology and infection control in spite of
      limited resources and compensation.
AB  - OBJECTIVE: Data on the resources and staff compensation of hospital epidemiology
      and infection control (HEIC) departments are limited and do not reflect current
      roles and responsibilities, including the public reporting of healthcare
      associated infections. This study aimed to obtain information to assist HEIC
      professionals in negotiating resources. METHODS: A 28-question electronic survey
      was sent via e-mail to all Society for Healthcare Epidemiology of America (SHEA)
      members in October 2006 with the use of enterprise feedback management solution
      software. The survey responses were analyzed using Microsoft Excel. RESULTS:
      Responses were received from 526 (42%) of 1,255 SHEA members. Of the respondents,
      84% were doctors of medicine (MDs) or doctors of osteopathy (DOs), 6% were
      registered nurses, and 21% had a master of public health or master of science
      degree. Sixty-two percent were male (median age range, 50-59 years). Their
      practice locations varied across the United States and internationally. Two
      thirds of respondents practiced in a hospital setting, and 63% were the primary
      or associate hospital epidemiologist. Although 91% provided HEIC services, only
      65% were specifically compensated. In cases of antimicrobial management, patient
      safety, employee health, and emergency preparedness, 75%-80% of respondents
      provided expertise but were compensated in less than 25% of cases. Of the US
      based MD and DO respondents, the median range of earnings was $151,000-$200,000,
      regardless of their region (respondents selected salary ranges instead of
      specifying their exact salaries). Staffing levels varied: the median number of
      physician full-time equivalents (FTEs) was 1.0 (range, 1-5); only about 25% of
      respondents had 3 or more infection control practitioner FTEs. CONCLUSIONS: Most
      professionals working in HEIC have had additional training and provide a wide,
      growing range of services. In general, only traditional HEIC work is compensated
      and at levels much less than the time dedicated to those services. Most HEIC
      departments are understaffed. These data are essential to advocate for needed
      funding and resources as the roles of HEIC departments expand.

PMID- 20039801
TI  - A case of seronegative HIV-1 infection.
AB  - Patients infected with human immunodeficiency virus type 1 (HIV-1) typically
      seroconvert within weeks of primary infection. In rare cases, patients do not
      develop antibodies against HIV-1 despite demonstrable infection. We describe here
      a human leukocyte antigen (HLA)-B*5802-positive individual who presented with
      acquired immune deficiency syndrome despite repeatedly negative HIV-1 antibody
      screening test results. Phylogenetic analysis of env clones revealed little
      sequence diversity, and weak HIV-1-specific CD8(+) T cell responses were present
      to Gag epitopes. The patient seroconverted after immune reconstitution during
      receipt of highly active antiretroviral therapy. Lack of an antibody response to
      HIV-1 is rare and appears to be due to a defect in HIV-1-specific immunity rather
      than infection with attenuated virus.

PMID- 20039802
TI  - Immunological reactivity of blood from healthy humans to the rAls3p-N vaccine
      protein.
AB  - We determined reactivity of human blood to a vaccine based on the recombinant N
      terminus of candidal Als3p (rAls3p-N) in preparation for future clinical trials.
      Healthy donor plasma had high immunoglobulin G titers (median, 1:51,200) and
      lower immunoglobulin A (median, 1:3,200) and immunoglobulin E (median, 1:128)
      titers to rAls3p-N by enzyme-linked immunosorbent assay. rAls3p-N stimulated
      interferon gamma (IFN-gamma) and interleukin (IL)-17, but not IL-4, from donor
      lymphocytes by enzyme-linked immunosorbent spot assay and IL-12 p70, IFN-gamma,
      IL-17, and IL-10 by cytometric bead array. Donors reacted to diverse
      immunodominant epitopes. Thus, facile humoral and cellular assays can monitor
      immune responses to the rAls3p-N vaccine in planned clinical trials.

PMID- 20039803
TI  - Piglet models of acute or chronic Clostridium difficile illness.
AB  - We examined the piglet model of Clostridium difficile illness (CDI) in humans,
      because swine are naturally susceptible to C. difficile. The piglet is a
      reproducible model of acute or chronic CDI with characteristic pseudomembranous
      colitis. Germ-free piglets were consistently and extensively colonized after oral
      challenge with the human strain 027/BI/NAP1, establishing an infectious dose-age
      relationship. This allowed a demarcation between acute fatal and chronic models.
      The clinical manifestations of disease inclusive of gastrointestinal and systemic
      symptoms and characteristic mucosal lesions of the large bowel (including
      pseudomembranous colitis) are described. Additionally, we demonstrate the
      presence of toxins in feces, body fluids, and serum and a significant elevation
      in interleukin 8 levels in animals with severe disease. We conclude that piglets
      infected with C. difficile mimic many of the key characteristics observed in
      humans with CDI and are suitable animals in which to investigate the role played
      by virulence attributes, drug efficacy, and vaccine candidates.

PMID- 20039804
TI  - Risk of myocardial infarction in patients with HIV infection exposed to specific
      individual antiretroviral drugs from the 3 major drug classes: the data
      collection on adverse events of anti-HIV drugs (D:A:D) study.
AB  - BACKGROUND. The risk of myocardial infarction (MI) in patients with human
      immunodeficiency virus (HIV) infection has been assessed in 13 anti-HIV drugs in
      the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. METHODS.
      Poisson regression models were adjusted for cardiovascular risk factors, cohort,
      calendar year, and use of other antiretroviral drugs and assessed the association
      between MI risk and cumulative (per year) or recent (current or in the past 6
      months) use of antiretroviral drugs, with >30,000 person-years of exposure.
      RESULTS. Over 178,835 person-years, 580 patients developed MI. There were no
      associations between use of tenofovir, zalcitabine, zidovudine, stavudine, or
      lamivudine and MI risk. Recent exposure to abacavir or didanosine was associated
      with an increased risk of MI. No association was found between MI risk and
      cumulative exposure to nevirapine, efavirenz, nelfinavir, or saquinavir.
      Cumulative exposure to indinavir and lopinavir-ritonavir was associated with an
      increased risk of MI (relative rate [RR] per year, 1.12 and 1.13, respectively).
      These increased risks were attenuated slightly (RR per year, 1.08 [95% confidence
      interval {CI}, 1.02-1.14] and 1.09 [95% CI, 1.01-1.17], respectively) after
      adjustment for lipids but were not altered further after adjustment for other
      metabolic parameters. CONCLUSIONS. Of the drugs considered, only indinavir,
      lopinavir-ritonavir, didanosine, and abacavir were associated with a
      significantly increased risk of MI. As with any observational study, our findings
      must be interpreted with caution (given the potential for confounding) and in the
      context of the benefits that these drugs provide.

PMID- 20039805
TI  - Cardiac risk: not so simple.

PMID- 20039806
TI  - A novel type of influenza vaccine: safety and immunogenicity of replication
      deficient influenza virus created by deletion of the interferon antagonist NS1.
AB  - BACKGROUND. The nonstructural protein NS1 of influenza virus counteracts the
      interferon-mediated immune response of the host. By deleting the open reading
      frame of NS1, we have generated a novel type of influenza vaccine. We studied the
      safety and immunogenicity of an influenza strain lacking the NS1 gene (DeltaNS1
      H1N1) in healthy volunteers. METHODS. Healthy seronegative adult volunteers were
      randomized to receive either a single intranasal dose of the DeltaNS1-H1N1 A/New
      Caledonia vaccine at 1 of 5 dose levels (6.4, 6.7, 7.0, 7.4, and 7.7 log(10)
      median tissue culture infective dose) (n = 36 recipients) or placebo (n = 12
      recipients). RESULTS. Intranasal vaccination with the replication-deficient
      DeltaNS1-H1N1 vaccine was well tolerated. Rhinitis-like symptoms and headache
      were the most common adverse events identified during the 28-day observation
      period. Adverse events were similarly distributed between the treatment and
      placebo groups. Vaccine-specific local and serum antibodies were induced in a
      dose-dependent manner. In the highest dose group, vaccine-specific antibodies
      were detected in 10 of 12 volunteers. Importantly, the vaccine also induced
      neutralizing antibodies against heterologous drift variants. CONCLUSIONS. We show
      that vaccination with an influenza virus strain lacking the viral interferon
      antagonist NS1 induces statistically significant levels of strain-specific and
      cross-neutralizing antibodies despite the highly attenuated replication-deficient
      phenotype. Further studies are warranted to determine whether these results
      translate into protection from influenza virus infection. TRIAL REGISTRATION.
      ClinicalTrials.gov identifier: NCT00724997 .

PMID- 20039812
TI  - Do lung disease patients need supplemental oxygen at high altitude?
AB  - As medical care and the quality of life for patients with lung disease improve,
      many of these individuals may engage in various forms of travel, including,
      possibly, travel to high altitude. Because the hypobaric hypoxia at high altitude
      may cause severe hypoxemia or impaired exercise tolerance in these patients,
      clinicians may be asked to assess whether they should use supplemental oxygen
      during their planned sojourn. This review considers this question in greater
      detail. After considering how the issue is approached in commercial airplane
      flight, we consider changes in oxygenation in lung disease patients in ambient
      hypoxia, the complications associated with such changes, tools for predicting the
      degree of hypoxemia at high altitude and important logistical issues associated
      with traveling with supplemental oxygen. The review concludes by providing
      tentative recommendations for assessing which patients should travel with
      supplemental oxygen. Patients already on supplemental oxygen at baseline should
      increase their flow rates at high altitude; patients with sufficiently severe
      disease who are not on such therapy should undergo pretravel assessment to
      determine the likely degree of hypoxemia at high altitude, with hypoxia altitude
      simulation testing being the preferred modality for this assessment. Those
      patients who develop symptomatic hypoxemia during such testing should travel with
      supplemental oxygen; those who remain asymptomatic or maintain adequate
      oxygenation may travel without oxygen, but they should have plans to monitor
      symptoms and oxygen saturation following arrival and arrange for oxygen therapy
      if necessary.

PMID- 20039807
TI  - Cytomegalovirus reinfections in healthy seroimmune women.
AB  - Cytomegalovirus (CMV) reinfections have been associated with damaging congenital
      infection and adverse outcomes in transplant recipients. To determine the
      frequency of and risk factors for CMV reinfections, 205 seropositive women were
      followed up prospectively. The appearance of new antibody specificity against 1
      of 4 polymorphic epitopes was considered as evidence of CMV reinfection.
      Approximately one-third of the study participants (59 [29%] of 205) were noted to
      have CMV reinfection during follow-up. None of the exposure factors were
      associated with CMV reinfection. Women with antibodies against at least 1 of the
      4 antigens at baseline had a 63% decreased risk of reinfection, suggesting a
      protective role for strain-specific immunity.

PMID- 20039813
TI  - Blood pressure responses in young adults first exposed to high altitude for 12
      months at 3550 m.
AB  - To determine the changes in blood pressure (BP) and related variables in sea
      level young adults with chronic exposure to high altitude, a longitudinal study
      was performed in male army recruits (n = 346; age 17.9 +/- 0.1 yr; BMI, 22.5 +/-
      0.3 kg/m(2)) first exposed to 3550-m altitude for 12 months. Fifty male recruits
      (age 17.8 +/- 0.6 and BMI 22.6 +/- 0.3 kg/m(2)) never exposed to altitude were
      used as controls. A sustained higher mean diastolic BP (DBP) (82.1 +/- 1.0 mmHg
      at month 3; 81.3 +/- 0.9 mmHg at month 12) was observed, compared to first
      exposure and the control group (p < 0.001). The BP values were always higher than
      those of the sea-level control group (systolic blood pressure (SBP) 109 +/- 2.3
      and DBP 67.4 +/- 0.8; p < 0.001), and a large proportion of subjects steadily
      presented overoptimal values for either systolic BP (SBP) (64%) or DBP (77%) and
      hypertensive DBP values (40%). The higher DBP was associated with lower Sao(2)
      (OR = 0.919; p < 0.05). In addition, the acute mountain sickness (AMS) score
      showed a slight decrease during re-exposure (3.9 +/- 0.3 vs.3.4 +/- 0.3; p <
      0.001) and an inverse association to the before-descending Sao(2) at month 3 (OR
      = 0.906, p < 0.01). These data suggest that BP stabilization can take longer than
      currently thought and that each parameter has a different profile of change.
      Further, a sustained high DBP should be a matter of epidemiological concern and
      emphasizes the need for BP monitoring among young lowlanders exposed to high
      altitude.

PMID- 20039814
TI  - Immobilization and splinting in mountain rescue. Official Recommendations of the
      International Commission for Mountain Emergency Medicine, ICAR MEDCOM, Intended
      for Mountain Rescue First Responders, Physicians, and Rescue Organizations.
AB  - Immobilization and splinting of fractures are essential to reduce morbidity and
      mortality in mountain rescue. Therefore, members of the International Commission
      for Mountain Emergency Medicine (ICAR MEDCOM) debated the results of a literature
      review carried out by the authors. Focusing on common immobilization and
      splinting techniques relevant to mountain rescue, a consensus document was
      formulated. Pain relief of appropriate speed of onset and strength should be
      available on scene. Spinal immobilization is recommended for all casualties that
      have sustained head or spine injury. The preferred method is a vacuum mattress
      with an appropriately sized rigid cervical collar. In such casualties, only those
      in an unsafe environment or with time-critical injuries should be evacuated
      before spinal immobilization is performed. In some casualties, the cervical spine
      may be cleared and a cervical collar may be omitted. In the presence of
      hemodynamic instability and where there is a suspicion of a fractured pelvis, an
      external compression splint should be applied. Splinting of a femoral shaft
      fracture is important to limit pain and life-threatening blood loss. If time
      allows, extremity fractures should be adequately splinted and, if the
      practitioner is skilled, a displaced fracture or joint dislocation should be
      reduced on scene with the use of appropriate analgesia.

PMID- 20039815
TI  - Impact of prolonged high altitude exposure on plasma prolactin in men: effect of
      age and ethnicity.
AB  - Hormonal changes during high-altitude (HA) exposure are important for normal
      adaptation to the new environment in lowlanders. Prolactin (PRL), a stress
      hormone, is involved in the regulation of fertility, immune response, osmotic
      balance, and angiogenesis. However, little is known about the effect of age and
      ethnicity on plasma PRL changes in men during prolonged HA exposure. The aim of
      this research was to examine possible age and ethnic variation in plasma PRL
      levels in men after 3 to 4 weeks of stay at HA (approximately 4500 m) in the
      Indian population. Lowlanders of Rajput (n = 49), Gorkha (n = 70), and South
      Indian (n = 40) ethnicities were studied at sea level (SL). They were taken to an
      altitude of approximately 4500 m where they stayed for 3 to 4 weeks. Another
      group of HA natives (Ladakhi, n = 65) was studied at similar altitude. Subjects
      were between 20 to 50 yr of age. At HA, plasma PRL showed a decrease in Rajputs
      and Gorkhas (p < 0.05), whereas there was an increase (p < 0.05) in South Indians
      when compared to SL. There was no age variation in PRL. PRL levels in HA natives
      were within the SL normal range observed in lowlanders. PRL response to HA stress
      in lowlanders is influenced by ethnicity. The exact cause for such differences in
      PRL secretion under HA stress is not clearly known. Further studies on the
      physiological regulation of PRL at HA are needed.

PMID- 20039816
TI  - Surface water quality along the Central John Muir Trail in the Sierra Nevada
      Mountains: coliforms and algae.
AB  - The John Muir Trail (JMT) in the Sierra Nevada Mountains of California is one of
      the most popular alpine wilderness trails in the United States, where backpackers
      depend on trailside water sources for more than 335 km (208 miles). This study
      addressed the risk of acquiring waterborne disease by analyzing prevalence and
      changes in coliform bacteria and Escherichia coli (E. coli) in lakes and streams
      adjacent to the central JMT. Chlorophyll-a levels were also measured as an
      indicator of high elevation eutrophication. Categories of environmental land use
      which might affect water quality were defined as: Pristine areas rarely traversed
      by humans; Backpack off-trail areas not traversed by pack or stock animals; and
      Multiuse areas with backpacker and animal use. We analyzed surface water at 36
      different sites three separate times over an eight week period in the summer of
      2008. Chlorophyll-a concentration increased significantly in Backpack and
      Multiuse sites over the summer months, but not in Pristine sites. Similar results
      were obtained for coliforms, with prevalence also increasing significantly over
      the summer months in Backpack and Multiuse sites. There was a much higher
      prevalence of E. coli in Multiuse sites compared to Pristine and Backpack sites.
      Our study provides evidence pack and stock animals serve as a source of microbial
      contamination of water along this section of trail.

PMID- 20039817
TI  - Effect of intermittent hypoxia on the reproduction of rats exposed to high
      altitude in the Chilean Altiplano.
AB  - Environmental parameters such as the large day-night temperature differences,
      high light radiation, and low humidity may have a synergistic effect with low
      oxygen pressure. To evaluate the effects of the exposure to intermittent chronic
      hypobaric hypoxia (ICHH) in nature on rat reproduction, a group of rats was
      alternately moved to a location at 3400 meters over sea level (moml) for 7 days
      and returned the subsequent week to sea level; this procedure was repeated six
      times. Hematological and reproductive parameters were measured and analyzed. At
      the end of the experimental protocol, hematocrit and hemoglobin concentrations
      were significantly greater in the ICHH group compared to the control group (Nx)
      (p < 0.05). The diameter of the seminiferous tubule and the height of the
      spermatogenic epithelium in ICHH rats presented a significant decrease in
      relation to Nx rats (p < 0.05). Consequently, the number of epididymal
      spermatozoa in the experimental animals decreased compared to normal rats, with
      no evidence of recovery after 84 days. The offspring of the different matings
      between normal and hypoxic animals decreased proportionally to hypoxia exposure.
      The low oxygen and the changes in testicular temperature homeostasis would
      provide a novel local mechanism to explain the decrease in sperm cell production
      and the reduced number of puppies born. The alterations of the reproductive
      parameters of the hypoxic female, plus testicular injuries and diminished sperm
      in males, result in a significant decrease in the reproductive activity of the
      animals.

PMID- 20039819
TI  - The impact of global warming on Mount Everest.
AB  - Global warming impacts a wide range of human activities and ecosystems. One
      unanticipated consequence of the warming is an increase in barometric pressure
      throughout the troposphere. Mount Everest's extreme height and resulting low
      barometric pressure places humans near its summit in an extreme state of hypoxia.
      Here we quantify the degree with which this warming is increasing the barometric
      pressure near Everest's summit and argue that it is of such a magnitude as to
      make the mountain, over time, easier to climb.

PMID- 20039818
TI  - Upregulation of arginase expression and activity in hypertensive rats exposed to
      chronic intermittent hypobaric hypoxia.
AB  - The aim of this study was to analyze the activity and expression levels of
      arginase I and II and to monitor the cardiovascular and hematological responses
      in tolerant and intolerant rats exposed to chronic intermittent hypobaric hypoxia
      (CIHH). Male Wistar rats (age: 3.0 +/- 0.4 months, weight: 250 +/- 25 g; n = 30)
      were randomly divided into two groups: CIHH2 x 2 (2 days hypoxia, 2 days
      normoxia, n = 20) and NX (normoxia, n = 10). The hypoxia was simulated in a
      hypobaric chamber at 428 torr. Tolerance was determined according to a previous
      protocol. Arginase activity was measured in lung and heart tissues, and the
      expression levels were determined by a (RT-PCR) assay in lung tissue. Results
      showed that the intolerants rats had lower body weight, higher hematocrit (Hct)
      (74 +/- 4% vs. 61 +/- 2%, p < 0.05), higher values of systolic blood pressure
      (SBP) (183 +/- 3.7 mmHg vs. 147 +/- 5.4 mmHg, p < 0.05), and higher arginase
      activity. In addition, RT-PCR analysis from lung tissue showed an overexpression
      of arginase II in the intolerant group (p < 0.01). However, tolerants had similar
      values as the NX group (p = ns). Further, a correlation was found between
      arginase activity and SBP in the heart (r(2) = 0.596, p < 0.001). An upregulation
      of arginase type II could be pivotal in understanding the pathogenesis of
      systolic hypertension and probably other phenomena associated with intermittent
      hypobaric hypoxia. A schematic explanation of these relations is proposed.

PMID- 20039820
TI  - Long-term renal function and stone recurrence after percutaneous nephrolithotomy
      in patients with renal insufficiency.
AB  - PURPOSE: We analyzed long-term results after percutaneous nephrolithotomy (PCNL)
      in patients with impaired renal function. PATIENTS AND METHODS: Nineteen (6.3%)
      of 300 patients who underwent PCNL had serum creatinine values above 1.4 mg/dL
      before surgery and were considered to have impaired renal function. Success rate
      of operation, recurrence rate, and renal functional status were evaluated.
      RESULTS: Mean follow-up time was 51.1 +/- 10.1 months. Sixteen patients completed
      the study, but three patients were lost to follow-up. The results of the
      operation were as follows: stone free in 50%, clinically insignificant residual
      fragments in 25%, and clinically significant residual fragments in 25% of the
      patients. Mean serum creatinine value was 2.30 +/- 0.56 mg/dL before surgery and
      2.67 +/- 1.41 mg/dL at the end of follow-up (p = 0.386). Creatinine values
      decreased to normal range in six patients (37.5%). Six patients (37.5%) had
      stable renal function (creatinine: 1.4-4 mg/dL). Creatinine values increased (>4
      mg/dL) in four patients (25%) who required renal replacement therapy. Three new
      patients progressed to end-stage renal failure. These three had insulin-dependent
      type II diabetes mellitus and one also had solitary kidney and atherosclerosis.
      Two patients (12.5%) had recurrences, one of these had hypercalciuria, and the
      other had infection stone. CONCLUSION: Our results indicated that most patients
      presenting with kidney-stone disease and renal insufficiency experience
      improvement or stabilization of renal function after PCNL. The patients with
      solitary kidney and those with conditions such as diabetes and atherosclerosis
      might be at greater risk for deterioration of renal function. Patients with
      metabolic abnormalities and infection stones might be at higher risk for
      recurrence.

PMID- 20039821
TI  - Percutaneous nephrolithotomy for proximal ureteral calculi with severe
      hydronephrosis: assessment of different lithotriptors.
AB  - PURPOSE: We compared the efficacy and safety of percutaneous nephrolithotomy
      (PCNL) with different intracorporeal lithotriptors for proximal ureteral stones
      in patients with severe hydronephrosis. PATIENTS AND METHODS: We retrospectively
      analyzed the records of 192 patients with proximal ureteral calculi and severe
      hydronephrosis who underwent PCNL between February 2003 and December 2007.
      Calculi were fragmented with a pneumatic lithotriptor in 44 patients (group 1),
      Swiss Lithoclast Master in 54 (group 2), low-power holmium:yttrium-aluminum
      garnet (YAG) laser in 56 (group 3) and high-power holmium:YAG laser in 38 (group
      4). Patients were assessed about 12 months postoperatively with intravenous
      urography and ultrasonography for late complications. Stone size, operative time,
      stone-free rate, and follow-up were analyzed in each group. RESULTS: Mean stone
      size for different groups were 16.2 +/- 2.8 mm, 16.6 +/- 2.1 mm, 16.0 +/- 2.7 mm,
      and 16.4 +/- 1.1 mm, respectively. Average operative time for different groups
      were 118 +/- 17 minutes, 81 +/- 10 minutes, 85 +/- 14 minutes, 110 +/- 16
      minutes, respectively. Group 2 and group 3 showed superior outcomes of shorter
      operative time (P = 0.000). The overall stone-free rate was 86.5%. As stratified
      by lithotriptors, the stone-free rate was 81.8% in group 1, 92.9% in group 2,
      88.9% in group 3, and 78.9% in group 4 (P = 0.190). No significant difference was
      found among the groups in terms of blood loss and postoperative hospital stay.
      Repeated PCNL or shockwave lithotripsy was necessary as an auxiliary procedure in
      26 patients. The overall complication rate was 18.2%; most complications were
      minor and insignificant. During the follow-up, ureteral stricture developed in 10
      patients and new renal stones developed in 4 patients. CONCLUSIONS: PCNL combined
      with Swiss Lithoclast Master or low-power holmium:YAG laser is the preferred
      endourologic modality for the management of proximal ureteral calculi in patients
      with severe hydronephrosis.

PMID- 20039822
TI  - Determination of success by objective scintigraphic criteria after laparoscopic
      pyeloplasty.
AB  - BACKGROUND AND PURPOSE: Laparoscopic pyeloplasty (LP) is a minimally invasive
      technique with high success rates that match open procedures. There are a variety
      of success definitions. We have defined and reported our success rate by
      objective renal scintigraphic criteria. We also compare our scintigraphic success
      with clinical success defined by absence of pain. PATIENTS AND METHODS: We
      reviewed retrospectively 111 adult cases of laparoscopic pyeloplasties. The
      Anderson-Hynes technique was used in 98% of cases. nonprimary pyeloplasties
      represented 12 cases of our series. Renal scintigraphic success rates were
      defined as: strict (T(1/2) <10 min), nonobstructive (T(1/2) <20 min), and
      technical success (improved T(1/2)). Of our patients, 83% had renal scintigraphy
      before and after surgery. RESULTS: Average operative time was 128 +/- 45 minutes,
      blood loss was 52 +/- 168 mL, and median postoperative hospital stay was 3 days.
      After surgery, T(1/2) was decreased by 26 minutes for a median time of 13
      minutes. Strict success was achieved in 61% of cases, while nonobstructive
      success and technical success were achieved in 86% and 93%, respectively. No
      difference in success was observed between primary and nonprimary cases. Clinical
      success (absence of symptoms) was achieved in 95% of LPs. We also show that 75%
      of patients who had obstruction after LP based on scintigraphic criteria were
      asymptomatic, showing a poor correlation between symptoms and obstruction.
      CONCLUSIONS: By defining success with renal scintigraphic criteria, we still
      obtain a high success rate. When using strict criteria, however, the success
      decreases and might identify patients at risk of late recurrence.

PMID- 20039823
TI  - Should percutaneous nephrolithotripsy be considered the primary therapy for lower
      pole stones?
AB  - PURPOSE: The efficacy of percutaneous nephrolithotripsy (PCNL) as a primary
      therapy for the treatment of lower pole caliceal lithiasis was determined.
      MATERIALS AND METHODS: We reviewed 144 consecutive files of patients, over a
      period of 10 years, with noncomplicated lower pole calculi, who underwent PCNL
      after a single unsuccessful session of extracorporeal shockwave lithotripsy
      (SWL). RESULTS: The stone-free rate for stones less than 10 mm was 95%. A 97%
      rate was accomplished for stones between 11 and 20 mm and a 98% rate for stones
      larger than 20 mm. PCNL achieved a mean overall stone-free rate of 96.7% after a
      3-month follow-up, regardless of stone size. PCNL outclasses SWL, when stratified
      by stone burden and lower pole location. No significant postoperative
      complications were encountered. CONCLUSION: PCNL is a safe and effective
      procedure for the management of lower pole caliceal calculi after a single
      unsuccessful SWL session. This procedure should be considered the primary method
      for the treatment of lower pole stones.

PMID- 20039824
TI  - Abnormalities in intracellular processing and expression of interferon-gamma
      receptor in adherent cells from lepromatous leprosy patients.
AB  - Peripheral blood mononuclear cells in lepromatous leprosy (LL) patients produce
      low levels of interferon-gamma (IFN-gamma) and interleukin-12 (IL-12), and these
      cells exhibit partial or complete deficiency in the IL-12 receptor. The behavior
      of the IFN-gamma receptor (IFN-gamma R) has not been described in cells from
      people with leprosy. We found higher levels of mRNA for IFN-gamma R1 and IFN
      gamma R2 in adherent cells stimulated with IFN-gamma and Mycobacterium leprae
      membrane proteins from LL patients compared with healthy subjects. Flow cytometry
      showed no significant difference in IFN-gamma R1 expression between LL patients
      and healthy subjects. Immunoblotting detected only the mature glycosylated form
      of the 61-67 kDa IFN-gamma R2 protein in healthy subjects. In contrast, cells
      from LL patients showed three different expression patterns: (1) the immature
      deglycosylated form of the 34.8 kDa IFN-gamma R2 protein, (2) the mature
      glycosylated 61-67 kDa form, and (3) both forms. Our data indicate the existence
      of abnormalities in the intracellular processing and protein expression of the
      IFN-gamma R in response to specific stimuli such as IFN-gamma and M. leprae
      membrane proteins in adherent cells of LL patients.

PMID- 20039825
TI  - Significant correlation between association of polymorphism in codon 10 of
      transforming growth factor-beta1 T (29) C with type 1 diabetes and patients with
      nephropathy disorder.
AB  - Type 1 diabetes is an autoimmune disease that is caused by destruction of
      pancreatic beta-cells. Type 1 diabetes is a heterogenic disease with
      environmental factors as well as genetic components. It is well established that
      environmental factors can exert their effects only on genetically susceptible
      patients. There is increasing evidence that genes outside the major
      histocompatibility complex (MHC) region contribute to the pathogenesis of type 1
      diabetes. Cytokines, due to their role in immune regulation, seem to play a
      crucial role in the pathogenesis of the disease. In order to investigate the
      immunosuppressive action of transforming growth factor-beta1 (TGF-beta1) in type
      1 diabetes, 388 patients with type 1 diabetes and 229 normal controls were
      genotyped for the TGF-beta1 T (29) C gene polymorphism. The TGF-beta1 T (29) C
      gene polymorphism was amplified using ARMS-PCR. Practical part of this work was
      conducted in Molecular Medicine Research Group, Peninsula Medical School,
      Plymouth, UK. However, statistical analyses were performed in Department of
      pathology, Salmaniya Medical Complex, Kingdom of Bahrain. From three different
      genotypes of TT, TC, and CC of the TGF-beta1 T (29) C, the TC frequency increased
      in patients with type 1 diabetes compared to normal controls, P value = 0.00001.
      The TC frequency was significantly higher in patients with diabetic nephropathy
      (DN) in comparison with diabetic control, P value = 0.007. Further, the CC
      frequency was significantly less in patients compared to healthy normal control
      subjects, P value = 0.005. Genetic variation at the TGF-beta1 gene polymorphism T
      (29) C located in codon 10 is likely to confer significant susceptibility to
      advanced DN in patients with T1D. This is a small case-control study in
      Caucasians to investigate the role of the TGF-beta1 gene polymorphism T (29) C
      located in codon 10 in the genetic predisposition to T1D and DN. To our
      knowledge, this is the first genetic report highlighting the dual effects of TGF
      beta1 in the onset of T1D as well as type 1 DN and can be a good model for
      extensive studies.

PMID- 20039826
TI  - Transvaginal hybrid natural orifice transluminal endoscopic surgery
      retroperitoneoscopy--the first human case report.
AB  - BACKGROUND: Retroperitoneal and transabdominal laparoscopic access to
      retroperitoneal organs became the golden standard for treatment of most adrenal
      and renal diseases. Natural orifice surgery is a promising concept in the
      evolution of minimal access surgery. The possibility of a natural orifice
      transluminal endoscopic surgery (NOTES) transvaginal retroperitoneal access to
      diagnose and perform retroperitoneal surgery was developed in our institution,
      aiming an alternative natural orifice less-invasive approach. METHODS:
      Institutional review board approval was obtained from the institution for
      clinical transvaginal NOTES. A 67-year-old woman (body mass index = 35.6 kg/m(2))
      found to have a large renal cyst situated in the lower pole with compression
      symptoms was subjected to the technique. Transvaginal retroperitoneal access was
      obtained by direct vision open technique, the space was digitally dissected, and
      a flexible two-channel colonoscope progressed the dissection to the left kidney.
      The cyst was dissected using endoscopic instruments, and resection was completed
      with use of two laparoscopic instruments because of peritoneal tear with loss of
      retropneumoperitoneum. RESULTS: NOTES transvaginal retroperitoneoscopy was
      performed, and anatomical landmarks, such as left ureter, inferior mesenteric
      artery (IMA), vena cava, and aorta, were identified. Insufflation and orientation
      were hazardous, because of constitutional fat, and operative time was 210
      minutes. Postoperative course was complicated by postoperative face and neck
      enphysema, which disappeared after few days. Observation was maintained for 4
      postoperative days, and the patient was discharged without other complications.
      Follow-up at 30 days was uneventful. CONCLUSION: This first human procedure using
      flexible transvaginal retroperitoneoscopy showed feasibility of the access, but
      inadequate instruments led to technical difficulties for therapeutical purposes.
      However, the new concept of minimally invasive NOTES retroperitoneoscopy may open
      new therapeutic indications in clinical practice in the near future.

PMID- 20039827
TI  - Robot-assisted laparoscopic radical prostatectomy in patients with previous
      abdominal surgery: a novel laparoscopic adhesiolysis technique.
AB  - PURPOSE: We evaluated the feasibility and outcomes of performing a novel
      laparoscopic adhesiolysis technique before robot-assisted laparoscopic radical
      prostatectomy (RALRP) in patients with previous abdominal surgery. PATIENTS AND
      METHODS: A total of 18 men with incision scars from previous abdominal surgeries
      underwent RALRP. A 12-mm trocar was placed at the lateral lower quadrant away
      from the incision site, and a teaching laparoscope was introduced into the
      peritoneal cavity. Meticulous adhesiolysis was performed through a single trocar
      to subsequently allow safe placement of additional robotic trocars. Age, type of
      previous surgery, total operative time, console time, anastomosis time, estimated
      blood loss, transfusion rate, complications, and conversion rate were recorded.
      RESULTS: All patients had multiple abdominal surgeries. Mean operative time was
      297 minutes, mean console time was 194 minutes, and mean estimated blood loss was
      241 mL. No access-related complication and no conversion to open surgery
      occurred. CONCLUSION: This novel laparoscopic technique of adhesiolysis with a
      teaching laparoscope through a single trocar facilitates safe placement of
      trocars and accomplishment of RALRP in patients with previous abdominal surgery.

PMID- 20039828
TI  - Fever after shockwave lithotripsy--risk factors and indications for prophylactic
      antimicrobial treatment.
AB  - PURPOSE: To identify risk factors for fever after shockwave lithotripsy (SWL) and
      suggest guidelines for prophylactic antimicrobial treatment. PATIENTS AND
      METHODS: Between 1985 and 2007, a total of 15,324 SWL procedures were performed
      in our institution using the Dornier HM3 lithotripter. Because stone analyses
      were not available in the majority of patients, management of stones larger than
      2 cm in diameter were excluded from this analysis to minimize the ratio of
      struvite stones as a possible cause for postprocedural fever. In this analysis,
      11,500 SWL treatments were included. Clinical parameters before, during, and
      after treatments were prospectively registered using a computerized database.
      Potential risk factors for fever after SWL were evaluated. RESULTS: Fever >38.0
      degrees C developed in 161 (1.4%) patients. The risk factors for fever after SWL
      were: A positive urine culture (P < 0.05), an indwelling nephrostomy tube or
      stent during the procedure (P < 0.001), lithotripsy of kidney or upper ureteral
      stones (P < 0.05) and preoperative symptomatic urinary tract infection (UTI) (P <
      0.05) or sepsis (P < 0.05). Lithotripsy of mid and lower ureteral stones, stone
      size, and the use of ureteral catheters during the procedures were not associated
      with increased risk of fever after SWL. CONCLUSIONS: Fever (>38.0 degrees C)
      develops in only 1.4% of the patients undergoing SWL. Therefore, prophylactic
      antibiotic treatment is not indicated in all patients. Selective prophylactic
      treatment is recommended in patients who present with UTI, kidney or upper
      ureteral stones, and those for whom a nephrostomy tube or stent is necessary.

PMID- 20039830
TI  - Refractive and reflective image distortion during lower tract endoscopy--a
      potential cause of misdiagnosis.
AB  - Flexible cystoscopy is well established in urological practice. We present a
      unique image obtained during bladder inspection, illustrating visual refractive
      distortion, which highlights the potential difficulty in optical interpretation.

PMID- 20039829
TI  - Comparative assessment of laparoscopic single-site surgery instruments to
      conventional laparoscopic in laboratory setting.
AB  - INTRODUCTION: Laparoendoscopic single-site surgery (LESS) represents the latest
      innovation in laparoscopic surgery. We compare in dry and animal laboratory the
      efficacy of recently introduced pre-bent instruments with conventional
      laparoscopic and flexible instruments in terms of time requirement,
      maneuverability, and ease of handling. MATERIALS AND METHODS: Participants of
      varying laparoscopic experience were included in the study and divided in groups
      according to their experience. The participants performed predetermined tasks in
      dry laboratory using all sets of instruments. An experienced laparoscopic surgeon
      performed 24 nephrectomies in 12 pigs using all sets of instruments. Single port
      was used for all instrument sets except for the conventional instruments, which
      were inserted through three ports. The time required for the performance of dry
      laboratory tasks and the porcine nephrectomies was recorded. Errors in the
      performance of dry laboratory tasks of each instrument type were also recorded.
      RESULTS: Pre-bent instruments had a significant advantage over flexible
      instruments in terms of time requirement to accomplish tasks and procedures as
      well as maneuverability. Flexible instruments were more time consuming in
      comparison to the conventional laparoscopic instruments during the performance of
      the tasks. There were no significant differences in the time required for the
      accomplishment of dry laboratory tasks or steps of nephrectomy using conventional
      instruments through appropriate number of ports in comparison to pre-bent
      instruments through single port. DISCUSSION: Pre-bent instruments were less time
      consuming and with better maneuverability in comparison to flexible instruments
      in experimental single-port access surgery. Further clinical investigations would
      elucidate the efficacy of pre-bent instruments.

PMID- 20039831
TI  - Incidentally discovered inverted papilloma of the urinary bladder in patients
      with lower urinary tract symptoms.
AB  - BACKGROUND AND PURPOSE: Inverted urothelial papilloma (IP) is an uncommon
      urothelial neoplasm. We aimed to determine the clinicopathologic characteristics
      of IP of the bladder and its association with prostate volume and lower urinary
      tract symptoms (LUTS). PATIENTS AND METHODS: From 1994 to 2008, 53 patients with
      urinary IP underwent transurethral resection of the bladder tumor (TURBT) at our
      institution. We reviewed the clinicopathologic characteristics of IP of the
      bladder and its association with prostate volume and LUTS. RESULTS: The patient
      population consisted of 46 men and 7 women with a mean age of 56 years (male to
      female ratio 6.6:1). The most common presenting symptom was LUTS (33 men and 3
      women). Of the 33 men with LUTS, the mean prostate volume before TURBT was 48.1
      cc (range 21.8-109.3 cc). IP was found incidentally in 14 men on transrectal
      ultrasonography (TRUS) and in 2 men during transurethral prostate resection. In
      IP located on the bladder neck of patients with benign prostatic hyperplasia
      (BPH), significantly higher obstructive symptoms and larger prostate volumes than
      that of other located IP with BPH were observed. CONCLUSIONS: This is the largest
      series of cases of urinary bladder IP reported from Korea. Despite the absence of
      agreement of its etiology, its presenting symptoms were related to LUTS and
      benign prostatic enlargement. TRUS may be helpful, especially in unresponsive
      patients with LUTS despite medical treatment.

PMID- 20039832
TI  - Complete supine percutaneous nephrolithotomy with lung inflation avoids the need
      for a supracostal puncture.
AB  - PURPOSE: The aim of this study was to evaluate the safety and efficacy of
      subcostal upper pole (UP) access in complete supine percutaneous nephrolithotomy
      (csPCNL). MATERIALS AND METHODS: From July 2008 to February 2009, we performed 20
      PCNLs in complete supine position. We present our experience of percutaneous
      approach in complete supine position to the renal superior calix, while insisting
      on renal displacement technique to facilitate the puncture of the superior
      calices and to decrease intrathoracic morbidity. The renal displacement technique
      was carried out with lung inflation. RESULTS: The percutaneous subcostal access
      of the renal UP was performed in 20 cases and no failure occurred. The overall
      stone-free rate was 85%, and the stone-free rate for upper calix was 95%. The
      mean operative time in our study was 102.25 +/- 41.56 minutes. The mean hospital
      stay was 92.4 +/- 30.43 hours. The transfusion rate as a complication was 1 (5%),
      and no intrathoracic complication was noted. CONCLUSIONS: The renal UP
      percutaneous access can be performed using several techniques. The superior calix
      was accessible in csPCNL with the renal displacement technique (lung inflation)
      subcostally while intrathoracic complications may be avoided. UP puncture in
      csPCNL with this technique was associated with minimal morbidity and avoids the
      need for a supracostal puncture, and the stone-free rate appeared to be more.

PMID- 20039833
TI  - Time-course for recovery of renal function after unilateral (single-tract)
      percutaneous access in the pig.
AB  - INTRODUCTION: The immediate (1-5 hours) response to percutaneous renal access
      (PERC) in pigs is vasoconstriction in the treated kidney. The present study
      determined the longer-term (72 hours) consequences of this surgical procedure.
      MATERIALS AND METHODS: Adult female pigs were anesthetized, and bilateral
      glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urine flow
      rate, and sodium excretion rate were measured before and 1 hour after sham PERC
      or unilateral, single-tract PERC using a balloon dilator system. Animals were
      allowed to regain consciousness and were then anesthetized 72 hours later for
      final measurements of bilateral renal hemodynamic and excretory function together
      with renal para-aminohippuric acid (PAH) extraction (a measure of tubular organic
      anion transport efficiency). RESULTS: Bilateral renal hemodynamics were unchanged
      in the sham-PERC-treated pigs over the 72-hour observation period. In contrast,
      both GFR and ERPF were reduced by approximately 55% in the PERC-treated kidney
      within 1 hour of access, and returned to pre-PERC levels within 72 hours. Renal
      hemodynamics were not significantly altered in the opposite, untreated kidney of
      the PERC-treated pigs. Renal PAH extraction was decreased in PERC-treated kidneys
      at 72 hours post-PERC. Both sham-PERC-treated and PERC-treated animals showed
      similar falls in urine flow rate and sodium excretion rate immediately after
      treatment and at 72 hours after PERC. CONCLUSIONS: Renal vasoconstriction
      characterized the acute response of the treated kidney to unilateral PERC,
      whereas impaired tubular function (reduced PAH extraction) with near-normal GFR
      and ERPF characterizes the later (72 hours) response to PERC.

PMID- 20039837
TI  - Wood smoke risk assessment: defining the questions.
AB  - Risk assessment provides a framework for combining and evaluating scientific data
      on source-to-health effects for contaminants that could potentially affect the
      health of human populations. It utilizes an integrated approach to hazard
      identification, dose response, exposure assessment, and risk characterization.
      Since the range of potential exposure scenarios is considerable, given the
      complexity of wood-smoke sources and emissions, there is a need for defining the
      critical characteristics for the key parameters leading to adverse health
      outcomes. During the International Biomass Smoke and Health Effects (IBSHE)
      conference at the University of Montana (August 2007), the breakout group
      entitled "Risk Assessment: Defining the Questions" was tasked with evaluating the
      current state of the science in regard to risk assessment involving biomass smoke
      exposure. As a result of these discussions, important data gaps and future
      research questions were identified that are reported in this article.

PMID- 20039839
TI  - Redox activity within the lysosomal compartment: implications for aging and
      apoptosis.
AB  - The lysosome is a redox-active compartment containing low-mass iron and copper
      liberated by autophagic degradation of metalloproteins. The acidic milieu and
      high concentration of thiols within lysosomes will keep iron in a reduced
      (ferrous) state, which can react with endogenous or exogenous hydrogen peroxide.
      Consequent intralysosomal Fenton reactions may give rise to the formation of
      lipofuscin or "age pigment" that accumulates in long-lived postmitotic cells that
      cannot dilute it by division. Extensive accumulation of lipofuscin seems to
      hinder normal autophagy and may be an important factor behind aging and age
      related pathologies. Enhanced oxidative stress causes lysosomal membrane
      permeabilization, with ensuing relocation to the cytosol of iron and lysosomal
      hydrolytic enzymes, with resulting apoptosis or necrosis. Lysosomal copper is
      normally not redox active because it will form non-redox-active complexes with
      various thiols. However, if cells are exposed to lysosomotropic chelators that do
      not bind all the copper coordinates, highly redox-active complexes may form, with
      ensuing extensive lysosomal Fenton-type reactions and loss of lysosomal
      stability. Because many malignancies seem to have increased amounts of copper
      containing macromolecules that are turned over by autophagy, it is conceivable
      that lysosomotropic copper chelators may be used in the future in ROS-based
      anticancer therapies.

PMID- 20039838
TI  - The hypoxia-inducible factor-2alpha is stabilized by oxidative stress involving
      NOX4.
AB  - The hypoxia-inducible factor-2alpha (HIF-2alpha) contributes to the vascular
      response to hypoxia. Hypoxia inhibits prolyl hydroxylation of the N-terminal
      transactivation domain (N-TAD), thus preventing binding of the von Hippel-Lindau
      protein (pVHL) and proteasomal degradation; additionally, hypoxia inhibits
      asparagyl hydroxylation of the C-TAD, thus diminishing cofactor recruitment.
      Reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) have been shown
      to control vascular functions and to promote vascular remodeling. However,
      whether HIF-2alpha, ROS, and NOXs are linked under such nonhypoxic conditions is
      unclear. We found that activation of NOX4 by thrombin or H(2)O(2) increased HIF
      2alpha protein because of decreased pVHL binding in pulmonary artery smooth
      muscle cells (PASMCs). Thrombin, H(2)O(2), and NOX4 overexpression increased HIF
      2alpha N-TAD and C-TAD activity, which was prevented by ascorbate treatment or
      mutation of the hydroxylation sites in the TADs. HIF-2alpha also mediated
      induction of plasminogen activator inhibitor-1 and the proliferative response to
      thrombin, H(2)O(2), or NOX4 overexpression. Thus, ROS derived from NOX4 in
      response to thrombin stabilize HIF-2alpha by preventing hydroxylation of the N-
      and C-TAD, thus allowing formation of transcriptionally active HIF-2alpha, which
      promotes PASMC proliferation. Together, these findings present the first evidence
      that HIF-2alpha is critically involved in the ROS-regulated vascular remodeling
      processes.

PMID- 20039841
TI  - The ongoing development of community mental health services in Japan: utilizing
      strengths and opportunities.
AB  - OBJECTIVE: The aim of this study was to identify opportunities for the
      development of best practice community mental health care models in Japan using
      key information extracted from the Asia-Pacific Community Mental Health
      Development Project, site visits conducted on community mental health models, and
      discussion on service delivery with mental health leaders in government, clinical
      services and community. CONCLUSION: In terms of hospital-based care, Japan has
      the highest number of psychiatric beds and highest ratio of beds per capita in
      the world. Strategies to address the disproportionate balance of mental health
      service components are clearly needed. While progress and initiatives in
      community-based mental health services are promising, there are significant
      challenges facing the mental health system in Japan. There is a need to expand
      the scope, quantity and distribution of best practice community mental health
      services in Japan. The available funding and human resource could be further
      directed to effective and culturally appropriate community-based services.
      Increased leadership capacity and confidence in the mental health workforce at
      all levels should be addressed effectively.

PMID- 20039840
TI  - The Eating Disorders Outreach Service: enabling clinicians statewide to treat
      eating disorders.
AB  - OBJECTIVE: The aim of this paper is to describe the Eating Disorders Outreach
      Service (EDOS), which supports clinicians in the treatment and management of
      eating disorder patients across Queensland. EDOS's mandate is to facilitate
      intake to the specialist inpatient and outpatient services at the Royal Brisbane
      and Women's Hospital (RBWH) and to provide eating disorders education and
      consultation liaison to clinicians statewide. METHOD: EDOS provides services in
      four key areas: intake facilitation, service development, education and training,
      and consultation liaison. Each area is described in detail. RESULTS: EDOS has
      grown since its inception to currently comprise a full-time team manager and a
      number of specialist clinician positions in psychiatry, nursing, dietetics,
      social work and psychology. The Service has become an integral part of the RBWH
      Adult Eating Disorders Service, providing statewide assessment and treatment
      recommendations, consultation liaison services and specialist intervention
      programs. CONCLUSIONS: EDOS has been successful in facilitating patient access to
      local general medical and psychiatric facilities. EDOS also plays a significant
      leadership role in the development of effective statewide networking forums for
      clinicians and key stakeholders, in inservice delivery and in the provision of
      evidence-based educational opportunities, each of which has contributed to
      improved access to services for eating disorder patients.

PMID- 20039842
TI  - The Queensland Mental Health Clinical Collaborative and the management of
      schizophrenia.
AB  - OBJECTIVE: This paper describes the development of a collaborative group of
      mental health clinicians who have come together to improve practice in adult
      acute mental health settings for the inpatient management of schizophrenia.
      METHOD: Sixteen acute adult mental health inpatient services across Queensland
      worked together to develop clinical indicators related to the inpatient treatment
      of schizophrenia. Data collection was conducted by using information available on
      existing databases and through statewide chart audits using scannable form
      technology. Through a secure intranet site, and statewide forums, clinicians were
      able to access information on clinical indicators enabling them to compare their
      site data to peer and state data. RESULTS: Available data from 15 of the 16 sites
      provided information on clinical indicators including average length of stay, 28
      day readmission rates, antipsychotic prescribing, medication dose and the use of
      multiple antipsychotic medications at discharge. CONCLUSIONS: The formation of
      the Mental Health Clinical Collaborative has brought together clinicians across
      the State to develop clinical indicators and openly discuss ideas to inform and
      improve clinical practice. This process has been effective in improving the
      quality of routinely collected information across the State and in engaging
      clinicians in using health information to drive clinical practice.

PMID- 20039844
TI  - Effects of sevoflurane on collagen production and growth factor expression in
      rats with an excision wound.
AB  - BACKGROUND: Sevoflurane is a widely used inhalation anesthetic, but there are no
      studies on its effect on the wound-healing process. This study was undertaken to
      evaluate the effect of exposure time to sevoflurane on wound healing. METHOD:
      Male Sprague-Dawley rats were used. Two circular full-thickness skin defects 8 mm
      in diameter were made on the dorsum of the rats. The animals were divided into
      six groups according to exposed gas type and time: S1 (sevoflurane, 1 h), S4
      (sevoflurane, 4 h), S8 (sevoflurane, 8 h), O1 (oxygen, 1 h), O4 (oxygen, 4 h),
      and O8 (oxygen, 8 h). The surface area of the wounds was measured 0, 1, 3, and 7
      days after surgery. Separately, the mean blood pressures (MBP) and arterial
      oxygen pressures (PaO(2)) were monitored during the sevoflurane exposure.
      Collagen type I production and transforming growth factor-beta1 (TGF-beta1) and
      basic fibroblast growth factor (bFGF) expression on the wound surface were
      analyzed. Routine histological analysis was also performed. RESULT: Exposure
      duration to sevoflurane had no influence on MBP and PaO(2). The reduction in
      wound size and collagen type I production was delayed in S8. The expression of
      TGF-beta1 and bFGF on the wound surface in S8 was significantly attenuated in S8.
      The histology of the S8 demonstrated a delayed healing status. CONCLUSIONS:
      Prolonged exposure to sevoflurane might alter the inflammatory phase of the wound
      healing process by attenuation of growth factor expression such as TGF-beta1 and
      bFGF and subsequently by reduced collagen production.

PMID- 20039845
TI  - Testing whether the epidural works: too time consuming?
AB  - BACKGROUND: When using epidural anaesthesia (EDA) for pain relief after major
      surgery, a failure rate of 10% is common. A crucial step in improving the care of
      patients with EDA is to define the position of the epidural catheter. The aim of
      this study was to investigate how much time it takes to determine whether the
      block is sufficient by assessing the extent of loss of cold sensation before
      induction of anaesthesia. METHODS: One hundred patients listed for abdominal
      surgery were included in the study. After an epidural catheter had been inserted
      and an intrathecal or an intravenous position had been made unlikely by the use
      of a test dose, the patient was given a bolus dose of local anaesthetic plus an
      opioid in the epidural catheter. The epidural block was tested every 2 min,
      starting at 5 min and ending at 15 min. When at least four segments were blocked
      bilaterally, the testing was stopped, the time was noted and the patient was
      anaesthetised. RESULTS: An epidural block was demonstrated after 5-6 min in 37
      patients, after 7-8 min in 43 additional patients and after 9-10 min in 15
      patients. In one patient, it took 12 min and in three patients, it took 15 min.
      In two patients, no epidural block could be demonstrated. CONCLUSION: Testing an
      epidural anaesthetic before the induction of anaesthesia takes only 5-10 extra
      minutes. Knowing whether the catheter is correctly placed means better quality of
      care, giving the anaesthetist better prerequisites for taking care of the patient
      post-operatively.

PMID- 20039847
TI  - Assessment of functional vision and its rehabilitation.
AB  - This article, based on a report prepared for the International Council of
      Ophthalmology (ICO) and the International Society for Low Vision Research and
      Rehabilitation (ISLRR), explores the assessment of various aspects of visual
      functioning as needed to document the outcomes of vision rehabilitation.
      Documenting patient abilities and functional vision (how the person functions) is
      distinct from the measurement of visual functions (how the eye functions) and
      also from the assessment of quality of life. All three areas are important, but
      their assessment should not be mixed. Observation of task performance offers the
      most objective measure of functional vision, but it is time-consuming and not
      feasible for many tasks. Where possible, timing and error rates provide an easy
      score. Patient response questionnaires provide an alternative. They may save time
      and can cover a wider area, but the responses are subjective and proper scoring
      presents problems. Simple Likert scoring still predominates but Rasch analysis,
      needed to provide better result scales, is gaining ground. Selection of questions
      is another problem. If the range of difficulties does not match the range of
      patient abilities, and if the difficulties are not distributed evenly, the
      results are not optimal. This may be an argument to use different outcome
      questions for different conditions. Generic questionnaires are appropriate for
      the assessment of generic quality of life, but not for specific rehabilitation
      outcomes. Different questionnaires are also needed for screening, intake and
      outcomes. Intake questions must be relevant to actual needs to allow
      prioritization of rehabilitation goals; the activity inventory presents a
      prototype. Outcome questions should be targeted at predefined rehabilitation
      goals. The Appendix cites some promising examples. The Low Vision Intervention
      Trial (LOVIT) is an example of a properly designed randomized control study, and
      has demonstrated the remarkable effectiveness of vision rehabilitation. It is
      hoped that further similar studies will follow.

PMID- 20039848
TI  - The optic nerve head assessed with HRT in 5-16-year-old normal children: normal
      values, repeatability and interocular difference.
AB  - PURPOSE: To investigate the normal values, repeatability and interocular
      difference of the optic nerve head, using Heidelberg retina tomography (HRT), in
      5-16-year-old full-term children with normal birth weights. METHODS: Fifty-six
      children with normal visual acuity and refraction were examined with HRT-II/III.
      Three examinations were performed on each eye. One eye was randomized for
      analyses of normal values and repeatability, and 54 eyes could be evaluated. The
      coefficient of variance and the intraclass correlation (ICC) were calculated, and
      the ISNT rule was noted. The correlation between right and left eyes and the
      limits of difference were determined in 50 pair of eyes. RESULTS: The mean values
      of disc and rim areas were 2.16 (SD 0.47) and 1.75 (SD 0.39) mm(2) respectively.
      The coefficients of variance varied between optic nerve parameters from 1.8% to
      21%, and the ICCs were >0.88. All parameters except retinal nerve fibre layer
      thickness correlated with the disc area. The ISNT rule was fulfilled in 56% of
      the eyes. The interocular difference was large but not statistically significant.
      CONCLUSION: We conclude that HRT can be used in children between 5 and 16 years
      of age, and normal values presented in the study can be used for comparison of
      children with optic nerve diseases. Because the assessment of rim area varied the
      least, it may be the parameter to use for follow-up. The normal large interocular
      difference should be taken into account when comparing eyes in the individual
      child.

PMID- 20039851
TI  - Sturge-Weber syndrome: decrease in intraocular pressure after transpupillary
      thermotherapy for diffuse choroidal haemangioma.
AB  - PURPOSE: To report intraocular pressure (IOP) reduction after selective and
      partial destruction of diffuse choroidal haemangioma (DCH) by transpupillary
      thermotherapy (TTT) using an 810 nm infrared diode laser in two patients with
      Sturge-Weber syndrome (SWS) having late-onset juvenile glaucoma (LOJG). METHODS:
      An interventional small case series. Laser spots (diameter, 1 mm) were applied to
      the tumour surface located outside the posterior pole. Energy level (600-1700 mW)
      and exposure time (1-4 seconds) were increased stepwise until the tumour
      exhibited a greyish discoloration. The treatment was split into 2-4 sessions.
      RESULTS: Before TTT, both patients had uncontrolled LOJG with an IOP of 23 mmHg
      (Case 1) and 45 mmHg (Case 2) in spite of topical medications. In both cases, TTT
      led to normalization of IOP to 15 mmHg and 24 mmHg, respectively, and stopped the
      progression of LOJG during a follow-up period of 6 years (Case 1) and 1 year
      (Case 2). Visual loss or other complications were not observed. CONCLUSIONS: Our
      study highlights the close link that exists between LOJG and DCH in SWS. A single
      treatment modality such as TTT may both reduce IOP in LOJG and help to prevent
      exudative retinal detachment in DCH. We believe that TTT is a good therapeutic
      option for SWS patients who have both DCH and LOJG.

PMID- 20039849
TI  - Timing of uveitis onset in oligoarticular juvenile idiopathic arthritis (JIA) is
      the main predictor of severe course uveitis.
AB  - PURPOSE: Aim of the present study was to validate a statistical model to predict
      a severe course of anterior uveitis (AU) in patients with juvenile idiopathic
      arthritis (JIA). METHODS: Consecutive patients with newly diagnosed uveitis have
      been followed for at least 1 year with a standardized protocol. For each patient,
      demographic, clinical and laboratory characteristics, including time interval
      between arthritis and uveitis onset, alpha(2)-globulins level at arthritis onset,
      number of uveitis relapses/year, ocular complications and therapy and visual
      acuity, have reported. The validation procedure included the assessment of
      sensitivity, specificity and efficiency of previously published statistical model
      (Zulian et al. J Rheumatol 2002; 29: 2446-2453) in a new inception cohort of
      patients during a short length follow-up. RESULTS: Sixty patients with JIA,
      followed at 14 paediatric rheumatology-ophthalmology centres in Italy, entered
      the study. The mean age at arthritis onset was 4.4 years (range 1.2-15.8 years),
      and the mean interval time between arthritis and uveitis onset was 1.8 years
      (range: 0.0-14.2 years). After the first AU, patients, followed for a mean of 3.2
      years, had a mean of 2.9 uveitis relapses. Twenty-two patients (36.7%) presented
      at least one complication. Using a probability cut-off value = 0.7, the
      statistical model revealed 80% sensitivity, 58% specificity and 65% efficiency.
      CONCLUSION: The time interval between arthritis and uveitis onset resulted as the
      main predictor of severe course uveitis in JIA. The statistical model was able to
      predict the development of a severe course in 8 of 10 patients.

PMID- 20039850
TI  - Corneal surface reconstruction using adult mesenchymal stem cells in experimental
      limbal stem cell deficiency in rabbits.
AB  - PURPOSE: To investigate the ability of mesenchymal stem cells (MSC) to
      transdifferentiate to corneal epithelial cells in experimental limbal stem cell
      deficiency in rabbits. METHODS: Total limbal stem cell deficiency was produced in
      21 right eyes of 21 New Zealand rabbits; 6 eyes served as controls (group 1, G1).
      After removal of the conjunctival overgrowth, five eyes received amniotic
      membrane transplantation (AMT; G2). In four eyes, autologous limbal stem cell
      transplantation from the healthy eye was performed with AMT (G3). In another six
      eyes, enriched autologous MSC were injected under the amniotic membrane (AM)
      (G4). Within 280 days, corneoscleral discs were analysed for goblet cells,
      cytokeratin (CK) 3/12, connexin 43, beta(1) -integrin, CK 19, alpha-enolase, p63
      and ATP-binding cassette transporter subtype G-2 (ABCG-2) distribution patterns.
      RESULTS: Cultivated MSC were positive for CK 3/12 and alpha-enolase, but negative
      for ABCG-2, p63 and connexin 43. On rabbit corneas, CK 3/12 was expressed in all
      corneal regions in all groups, but with significantly different intensities.
      Among all other parameters, expression levels of ABCG-2, beta(1) -integrin and
      connexin 43 were significantly different between the transplanted groups and the
      control group. After a mean follow-up time of 172 (47-280) days, goblet cells
      were rarely present in the central cornea (G1-4). CONCLUSION: CK 3/12 is not
      highly specific for differentiated corneal epithelium. Further, goblet cells are
      not a reliable marker for conjunctivalization in rabbits. Expression of ABCG-2,
      beta(1)-integrin and connexin 43 after mesenchymal stem cell transplantation may
      indicate their ability to maintain their stem cell character or to
      transdifferentiate to epithelial progenitor cells.

PMID- 20039852
TI  - Validation of tissue quality parameters for donor corneas, designated for
      emergency cases: corneal graft survival.
AB  - PURPOSE: To validate tissue quality parameters for donor corneas designated for
      emergency grafting for corneal graft survival. METHODS: In a longitudinal cohort
      follow-up study, 131 emergency penetrating grafts were studied. Grafts were
      performed with a pool of organ-cultured donor corneas designated for emergency
      grafting and prepared for immediate use with all safety tests performed.
      Assignation criteria were: corneas with a small superficial stromal opacity but
      meeting all selection criteria for PKP tissue and corneas without stromal
      opacity, but an endothelial cell density from 1800 to 2300 cells/mm(2) or mild
      polymegathism or pleomorphism. Cox multivariate regression analysis, Kaplan-Meier
      survival and log rank test were applied. RESULTS: Of the 131 keratoplasties, 115
      could be followed. One eye was lost during surgery because of an expulsive
      bleeding. In 15 cases, a conjunctival transplantation finished off the
      penetrating graft. Corneal graft survival was not significantly related to the
      presence of PKP quality of the donor endothelium, neither with a cloudy graft nor
      with endothelial decompensation as the cause of failure. Main risk factors for a
      failed graft were vascularization of the host cornea (p=0.0001), the presence of
      a systemic auto immune disease in the recipient (p=0.003) and the disease leading
      to the (imminent) perforation and emergency graft (p=0.021). CONCLUSION: A
      selected pool of donor corneas designated for emergency grafting that does not
      interfere with the scheduled procedures allows more efficient and safe use of
      donor tissue in case of a(n) (imminent) perforation. Corneal graft survival rates
      justify the criteria for selection.

PMID- 20039853
TI  - The outcome of cataract surgery measured with the Catquest-9SF.
AB  - PURPOSE: The purpose of this study was to use the Catquest-9SF to measure
      cataract surgery outcomes, and to use Rasch analysis to test the psychometric
      properties of this questionnaire, including its validity and responsiveness.
      METHODS: Patients were recruited as consecutive cataract surgery patients during
      1 month at six surgical units in Sweden (via the National Cataract Register). The
      patients completed the questionnaire before surgery and 3 months after. The
      Catquest-9SF data were assessed for fit to the Rasch model using version 3.63.2
      of the WINSTEPS software (Winsteps.com, Beaverton, OR, USA). Both preoperative
      and postoperative questionnaires were included in the analysis. The
      responsiveness to cataract surgery was calculated as the effect size. RESULTS:
      Completed questionnaires before and after surgery were received from 846
      patients. The Rasch analysis showed that the category thresholds were ordered.
      All items fit a single overall construct (infit range 0.79-1.40; outfit range
      0.74-1.40). The ability to discriminate different strata of person ability was
      good, with a real patient separation of 2.58 and patient separation reliability
      of 0.87. The questionnaire showed unidimensionality and was largely free from
      differential item functioning. The item difficulty was reasonably well targeted
      to both preoperative and postoperative patient ability. The Catquest-9SF Rasch
      score correlated significantly with visual acuity, and cataract surgery resulted
      in a significant improvement with an effect size of 1.8. CONCLUSION: The Catquest
      9SF shows excellent psychometric properties, as demonstrated by Rasch analysis.
      It is highly responsive to cataract surgery, and its brevity (nine items) makes
      it well suited for use in daily clinical practice.

PMID- 20039854
TI  - Retinal vascular events after intravitreal bevacizumab.
AB  - PURPOSE: To record retinal vascular events following intravitreal bevacizumab
      injection. METHODS: Collaborative multi-centre retrospective case series.
      RESULTS: Eight patients were documented to have central retinal artery occlusion
      (four patients), branch retinal artery occlusion, capillary occlusion, central
      retinal vein occlusion and branch retinal vein occlusion (one patient each)
      within 0-55 days (median 2 weeks) of intravitreal bevacizumab. All patients had
      several ocular and systemic risk factors for retinal vascular events: elevated
      intraocular pressure on discharge (four patients), pre-existent glaucoma (one
      patient), pre-existent ischaemic retinal vascular disorder (four patients),
      systemic hypertension (five patients), diabetes mellitus (three patients),
      coronary artery disease (four patients), carotid disease (three patients),
      smoking (two patients) and migraine (one patient). CONCLUSION: The retinal
      vascular events may be associated with the underlying ocular disease under
      treatment or with the underlying systemic disease, may be related to an increased
      intraocular pressure post-injection constraining further an already poor retinal
      perfusion, the vasoconstrictor effect of bevacizumab, or a combination of all
      three.

PMID- 20039856
TI  - Transient regression of choroidal neovascularization membrane after vitrectomy in
      age-related macular degeneration with vitreomacular traction syndrome.

PMID- 20039855
TI  - Reproducibility of retinal thickness measurements in patients with age-related
      macular degeneration using 3D Fourier-domain optical coherence tomography (OCT)
      (Topcon 3D-OCT 1000).
AB  - PURPOSE: Conventional time-domain optical coherence tomography (OCT) has become
      an important tool for following dry or exudative age-related macular degeneration
      (AMD). Fourier-domain three-dimensional (3D) OCT was recently introduced. This
      study tested the reproducibility of 3D-OCT retinal thickness measurements in
      patients with dry and exudative AMD. METHODS: Ten eyes with dry AMD and 12 eyes
      with exudative AMD were included in the study. Sets of three OCT 6 * 6-mm raster
      scans were taken by one operator. Mean retinal thickness was calculated for 36
      areas. Coefficients of variation (CoV) were calculated for each patient and area.
      For analysis, two separate areas (central and peripheral) were defined.
      Generalized estimating equations (GEEs) were applied to all 36 subfields in order
      to analyse possible differences in CoV and mean retinal thickness between dry and
      exudative AMD. RESULTS: Mean retinal thickness values were significantly larger
      in the central area in exudative AMD (p < 0.001). Mean CoV for exudative AMD was
      3.7% (standard deviation [SD] 1.4%). Mean CoV for dry AMD was 1.8 (SD 0.6%). The
      reproducibility of retinal thickness measurements was significantly less in
      exudative AMD (p = 0.009). CONCLUSIONS: Reproducibility of 3D-OCT retinal
      thickness measurements was good in both groups. However, reproducibility was
      significantly better in dry AMD than in exudative AMD.

PMID- 20039857
TI  - The role of CTGF in the diabetic rat retina and its relationship with VEGF and
      TGF-beta(2) , elucidated by treatment with CTGFsiRNA.
AB  - PURPOSE:  The critical association of connective tissue growth factor (CTGF) with
      diabetic retinopathy (DR) remains to be clarified. We detected alterations in the
      gene and protein expression of CTGF and related cytokines, including vascular
      endothelial growth factor (VEGF) and transforming growth factor-beta(2) (TGF
      beta(2) ), and their response to small interfering RNA (siRNA) targeting the CTGF
      (CTGFsiRNA) in the retina of diabetic rats. The relationships between CTGF, VEGF
      and TGF-beta(2) levels, as well as the degree of apoptosis in the diabetic
      retina, were also investigated. METHODS:   Diabetes was induced in rats by the
      beta-cell toxin streptozotocin (STZ). Retinas were obtained from control and
      diabetic rats and similar animals treated with CTGFsiRNA by intravitreal
      injection. mRNA level and protein expression of CTGF, VEGF and TGF-beta(2) were
      measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blotting, and located by immunohistochemistry. Retinal apoptosis was detected by
      TUNEL staining. RESULTS: The levels of CTGF, VEGF and TGF-beta(2) and the number
      of TUNEL-positive nuclei were significantly higher in diabetic retinas than in
      control retinas (p<0.01). The level of CTGF rose at 8weeks, earlier than levels
      of VEGF and TGF-beta(2) , which rose at 12weeks after the onset of diabetes. The
      difference was significant (p<0.05). siRNA-mediated inhibition of CTGF mRNA
      inhibited retinal VEGF and TGF-beta(2) and also resulted in a significant
      decrease in apoptosis. Significant correlations were found between CTGF and VEGF
      (p=0.009), CTGF and TGF-beta(2) (p=0.01), and apoptosis and these three cytokines
      (p<0.01) in the rat retina early in diabetes. CONCLUSIONS: These results suggest
      that the diabetes-mediated increase in CTGF upregulates VEGF and TGF-beta(2)
      expression and induces apoptosis in the retina. This elevation may be inhibited
      by treatment with CTGFsiRNA. Connective tissue growth factor may serve as a
      potential target for the prevention and treatment of DR.

PMID- 20039858
TI  - The trouble with drink: why ideas matter.
AB  - This paper builds upon the work of previous authors who have explored the
      evolution of ideas in the alcohol arena. With revisions in the relevant sections
      of ICD and DSM forthcoming, such matters are of considerable contemporary
      importance. The focus here will be upon the history of the last 200 years. The
      main themes to be explored include the flux of ideas on what, over time, has
      counted as the trouble with drink, ideas on the cause of the problem and the
      impact of this thinking on public action. Medical authorities of the late
      Enlightenment period made the revolutionary suggestion that habitual drunkenness
      constituted a disease, rather than a vice. The thread of that idea can be traced
      to the present day, but with an alternative perception of drink itself or alcohol
      related problems generally, as cause for concern, also having a lineage. There
      are several inferences to be drawn from this history: the need for vigilance lest
      disease formulations become stalking-horses for moralism and social control, the
      need to integrate awareness of alcohol dependence as a dimensional individual
      level problem, with a public health understanding of the vastly amorphous and at
      least equally important universe of alcohol-related problems; the dangers lurking
      in scientific reductionism when the problems at issue truly require a multi
      disciplinary analysis; and the need for global consensus rather than cultural
      imposition of ideas on what counts as the problem with drink.

PMID- 20039859
TI  - Drug prevention programmes for young people: where have we been and where should
      we be going?
AB  - AIM: Substance use by young people has long been a concern of western society,
      but opinion is mixed as to which prevention approach offers the greatest benefit,
      and whether indeed there is any benefit at all. This paper reviews the nature of
      prevention programmes, the research evidence that underpins these programmes and
      the prevention objectives against which effectiveness is measured. The aim of
      this is to create better understanding of the elements that maximize programme
      effectiveness, what can be achieved by prevention programmes and how programmes
      can be improved. FINDINGS: There is a range of prevention approaches for which
      there is evidence of effectiveness. Some are classroom-based; some focus upon
      parenting; some have substantial whole-of-school and community elements; and some
      target risk and protective factors in early childhood. All, however, are based
      substantially on the social influence model. In an attempt to improve practice
      lists of effective programmes have been developed, but there are concerns about
      the science behind selection. On balance, there is consistent evidence that
      social influence prevention programmes do have a small, positive effect on drug
      use, but this then raises the question as to whether harm, rather than use, would
      be the more worthwhile target for prevention. Prevention that seeks to reduce
      harm has been demonstrably effective, but has found little support in some
      jurisdictions. CONCLUSION: Research has created a progressively better
      understanding of how to optimize programme effectiveness and what can be achieved
      realistically by even the most effective programmes. However, further research is
      required to identify which, if any, particular approach offers greater promise.
      The effectiveness of harm reduction should be compared with more traditional
      abstinence and the additional effects of whole of school, parent and community
      elements need to be measured more accurately. Contemporary social influence
      prevention programmes are flawed, but the approach is still the best way of
      influencing drug use behaviour in young people as a whole. Evidence-based
      refinement is the best option for greater benefit.

PMID- 20039861
TI  - Profile of peripheral blood neutrophil cytokines in diabetes type 1 pregnant
      women and its correlation with selected parameters in the newborns.
AB  - PROBLEM: Interleukin (IL)-12, IL-10, tumor necrosis factor-alpha (TNF-alpha), IL
      6 and IL-8 alter as pregnancy progresses, implying continuous immune regulation
      associated with the maintenance of pregnancy. We aimed to evaluate the peripheral
      blood neutrophil-derived production of these cytokines in the course of pregnancy
      complicated by type 1 diabetes. METHOD: of study These parameters were measured
      in samples from healthy non-pregnant (C), diabetic non-pregnant (D), healthy
      pregnant (P) and pregnant diabetic (PD) women. RESULTS: Neutrophil-derived
      secretion of TNF-alpha and IL-12 increased along with progression of pregnancy in
      PD and P groups. The concentration of IL-10 from lipopolysaccharide (LPS)
      stimulated neutrophils increased during the course of uncomplicated pregnancy but
      decreased in diabetic pregnancy. Concentration of IL-8 decreased with the
      advancing gestational age in P and PD groups. LPS-stimulated neutrophil-derived
      IL-6 concentration increased only in PD patients. CONCLUSION: Our results show
      that diabetes creates pro-inflammatory environment thus potentially influencing
      the outcome of pregnancy. We conclude that neutrophil-derived cytokine production
      could contribute to the complications seen in pregnant women with type 1
      diabetes.

PMID- 20039860
TI  - Exposure to cannabis in popular music and cannabis use among adolescents.
AB  - BACKGROUND: Cannabis use is referenced frequently in American popular music, yet
      it remains uncertain whether exposure to these references is associated with
      actual cannabis use. We aimed to determine if exposure to cannabis in popular
      music is associated independently with current cannabis use in a cohort of urban
      adolescents. METHODS: We surveyed all 9th grade students at three large US urban
      high schools. We estimated participants' exposure to lyrics referent to cannabis
      with overall music exposure and content analyses of their favorite artists'
      songs. Outcomes included current (past 30 days) and ever use of cannabis. We used
      multivariable regression to assess independent associations between exposures and
      outcomes while controlling for important covariates. RESULTS: Each of the 959
      participants was exposed to an estimated 27 cannabis references per day
      [correction added on 19 January 2010, after first online publication: 40 has been
      changed to 27] (standard deviation = 73 [correction added on 19 January 2010,
      after first online publication: 104 has been changed to 73]). Twelve per cent (n
      = 108) were current cannabis users and 32% (n = 286) had ever used cannabis.
      Compared with those in the lowest tertile of total cannabis exposure in music,
      those in the highest tertile of exposure were almost twice as likely to have used
      cannabis in the past 30 days (odds ratio = 1.83; 95% confidence interval = 1.04,
      3.22), even after adjusting for socio-demographic variables, personality
      characteristics and parenting style. As expected, however, there was no
      significant relationship between our cannabis exposure variable and a sham
      outcome variable of alcohol use. CONCLUSIONS: This study supports an independent
      association between exposure to cannabis in popular music and early cannabis use
      among urban American adolescents.

PMID- 20039862
TI  - Tolerance mechanisms in pregnancy: a reappraisal of the role of class I paternal
      MHC antigens.
AB  - PROBLEM: Allogeneic pregnancies have a survival advantage over syngeneic
      pregnancies, and paternal Class I MHC antigens have been implicated. In humans,
      HLA-C and HLA-G and E are expressed by subpopulations of fetal trophoblast. In
      mice, Qa-2, a Class Ib antigen, and classical H-2K antigens have been described.
      However, the mechanism of prevention of embryo demise in utero has not been
      critically assessed, and a number of conflicting ideas have not been addressed.
      The alphabeta T-cell receptor recognizes peptide bound to the groove in Class I
      MHC, and peptides have profound effects on the interaction of KIR receptors on T
      and NK cells with Class I MHC. METHODS: Data on prevention of pregnancy loss
      (abortion) in poly IC-treated mice were reviewed along with information about
      prevention of losses in the abortion-prone CBA x DBA/2 model. This information
      was combined with data on paternal antigen expression at different times in
      pregnancy when key events determining outcome are thought to transpire, and role
      of tolerance signaling molecules such as CD200. Current data on models supporting
      a role for 'true' uterine NK cells (TuNKs) versus blood NK cells in the uterus
      (BuNKs) and role of MHC-KIR interaction were reviewed along with incompatible
      data in the literature. RESULTS: Whilst paternal Class I MHC appears important,
      there is an important role for paternal non-MHC minor antigens (small peptides)
      that bind to the antigen-presenting groove of Class I MHC. BuNKs along with
      CD8(+) T cells and Treg cells appear more important than TuNKs where the role of
      the latter appears primarily to promote angiogenesis. When during pregnancy the
      maternal immune system cells are first exposed to paternal Class I + peptide is
      uncertain, but at the time of implantation, if not earlier, seems likely.
      CONCLUSION: Suppression of pregnancy loss by paternal/embryo Class I MHC depends
      on the presence of paternal peptides. This greatly complicates existing models of
      Class I-KIR interactions in feto-maternal tolerance or rejection. It is important
      to consider all the data when devising explanatory models.

PMID- 20039864
TI  - Anaesthesia for proximal femoral fracture in the UK: first report from the NHS
      Hip Fracture Anaesthesia Network.
AB  - The aim of this audit was to investigate process, personnel and anaesthetic
      factors in relation to mortality among patients with proximal femoral fractures.
      A questionnaire was used to record standardised data about 1195 patients with
      proximal femoral fracture admitted to 22 hospitals contributing to the Hip
      Fracture Anaesthesia Network over a 2-month winter period. Patients were
      demographically similar between hospitals (mean age 81 years, 73% female, median
      ASA grade 3). However, there was wide variation in time from admission to
      operation (24-108 h) and 30-day postoperative mortality (2-25%). Fifty percent of
      hospitals had a mean admission to operation time < 48 h. Forty-two percent of
      operations were delayed: 51% for organisational; 44% for medical; and 4% for
      'anaesthetic' reasons. Regional anaesthesia was administered to 49% of patients
      (by hospital, range = 0-82%), 51% received general anaesthesia and 19% of
      patients received peripheral nerve blockade. Consultants administered 61% of
      anaesthetics (17-100%). Wide national variations in current management of
      patients sustaining proximal femoral fracture reflect a lack of research evidence
      on which to base best practice guidance. Collaborative audits such as this
      provide a robust method of collecting such evidence.

PMID- 20039865
TI  - The changing biological roles of melatonin during evolution: from an antioxidant
      to signals of darkness, sexual selection and fitness.
AB  - Melatonin is a molecule present in a multitude of taxa and may be ubiquitous in
      organisms. It has been found in bacteria, unicellular eukaryotes, macroalgae,
      fungi, plants and animals. A primary biological function of melatonin in
      primitive unicellular organisms is in antioxidant defence to protect against
      toxic free radical damage. During evolution, melatonin has been adopted by
      multicellular organisms to perform many other biological functions. These
      functions likely include the chemical expression of darkness in vertebrates,
      environmental tolerance in fungi and plants, sexual signaling in birds and fish,
      seasonal reproductive regulation in photoperiodic mammals, and immunomodulation
      and anti-inflammatory activity in all vertebrates tested. Moreover, its waning
      production during aging may indicate senescence in terms of a bio-clock in many
      organisms. Conversely, high melatonin levels can serve as a signal of vitality
      and health. The multiple biological functions of melatonin can partially be
      attributed to its unconventional metabolism which is comprised of multi
      enzymatic, pseudo-enzymatic and non-enzymatic pathways. As a result, several
      bioactive metabolites of melatonin are formed during its metabolism and some of
      the presumed biological functions of melatonin reported to date may, in fact, be
      mediated by these metabolites. The changing biological roles of melatonin seem to
      have evolved from its primary function as an antioxidant.

PMID- 20039863
TI  - Can sulfasalazine prevent infection-mediated pre-term birth in a murine model?
AB  - PROBLEM: Sulfasalazine (SASP) blocks activation of nuclear factor-kappa B (NF
      kappaB) in gestational tissues in vitro- one of the earliest signals in the
      inflammatory response. We hypothesized that the administration of SASP would
      reduce the rate of infection-mediated pre-term birth in a murine model. METHOD:
      of study CD-1 mice (n = 40) were assigned on gestational day (gd) 14.5 to 1 of 3
      treatments: (1) Sham infection and vehicle; (2) 10(4) CFU Escherichia coli and
      vehicle; or (3) 10(4) CFU E. coli and SASP (150 mg/Kg daily). Mice were observed
      twice daily and deliveries prior to gd 18.5 were considered pre-term. RESULTS:
      Significantly more mice delivered prior to gd 18.5 when infected with 10(4) CFU
      E. coli than sham-infected mice (P < 0.001) and this effect was significantly
      reduced in mice also treated with SASP (P = 0.002). SASP also tended to increase
      litter size (P = 0.060) and significantly increased weight of pups born to dams
      with intrauterine infections (P = 0.001). CONCLUSION: SASP reduced rates of pre
      term delivery and improved pregnancy outcomes for mice infected with 10(4) CFU E.
      coli. This suggests that SASP has the potential to play a role in strategies to
      prevent pre-term birth in women.

PMID- 20039866
TI  - One for all and all for one: the energetic benefits of huddling in endotherms.
AB  - Huddling can be defined as "an active and close aggregation of animals". It is a
      cooperative group behaviour, permitting individuals involved in social
      thermoregulation to minimize heat loss and thereby lower their energy
      expenditure, and possibly allowing them to reallocate the saved energy to other
      functions such as growth or reproduction. Huddling is especially important in the
      case of animals faced with high heat loss due to a high surface-to-volume ratio,
      poor insulation, or living in cold environments. Although numerous experimental
      studies have focused on the huddling behaviour of a wide range of species, to our
      knowledge, this is the first attempt to review the various implications of this
      widely used behavioural strategy. Huddling allows individuals to maximise energy
      savings by (1) decreasing their cold-exposed body surface area, (2) reducing
      their heat loss through warming of ambient temperatures surrounding the group,
      and (3) eventually lowering their body temperature through physiological
      processes. Huddling provides substantial energy savings and is estimated to
      reduce energy expenditure by between 6 and 53%. Broad variations in the energetic
      benefits of huddling depend on the number of individuals and species involved in
      huddles, the ambient temperatures to which individuals are exposed and the
      density of the aggregations. It has been shown that huddling individuals have
      increased survival, a lower food intake, a decreased body mass loss, increased
      growth rate, reduced water loss, and/or a more constant body temperature together
      with a significant reduction in metabolic rate. Though huddling has been studied
      widely, this review reveals the intricacies of this adaptive behaviour.

PMID- 20039868
TI  - The effect on outcome of peribulbar anaesthesia in conjunction with general
      anesthesia for vitreoretinal surgery.
AB  - The purpose of this study was to evaluate peri-operative outcome after
      vitreoretinal surgery when peribulbar anaesthesia is combined with general
      anaesthesia. Sixty adult patients undergoing elective primary retinal detachment
      surgery with scleral buckling or an encircling procedure received either
      peribulbar anaesthesia in conjunction with general anaesthesia or general
      anaesthesia alone. For peribulbar anaesthesia a single percutaneous injection of
      5-7 ml of local anaesthetic solution (0.75% ropivacaine with hyaluronidase 15
      iu.ml(-1)) was used. The incidence of intra-operative oculocardiac reflex and
      surgical bleeding interfering with the surgical field, postoperative pain and
      analgesia requirements, and postoperative nausea and vomiting were recorded. In
      the block group there was a lower incidence of oculocardiac reflex and surgical
      bleeding intra-operatively. Patients in the block group also had better
      postoperative analgesia and a lower incidence of postoperative nausea and
      vomiting compared with the group without a block. The use of peribulbar
      anaesthesia in conjunction with general anesthesia was superior to general
      anaesthesia alone for vitreoretinal surgery with scleral buckling.

PMID- 20039869
TI  - Predicting renal functional outcomes after surgery for renal cortical tumours: a
      multifactorial analysis.
AB  - OBJECTIVE: To examine the functional outcomes after radical (RN) and partial
      nephrectomy (PN) stratified by variables before and after surgery, using
      estimated glomerular filtration rate (eGFR), as nephrectomy is the standard
      treatment for localized renal tumours, but the risk of developing chronic kidney
      disease (CKD) increases after surgery. PATIENTS AND METHODS: We retrospectively
      analysed patients treated with PN or RN for renal cancer at one institution from
      1988 to 2008. Chronic renal function before and after surgery was measured using
      the eGFR computed using the Modification of Diet in Renal Disease equation. Four
      outcomes were measured: (i) presence of new-onset renal insufficiency (eGFR <60
      mL/min/1.73m(2)); (ii) the percentage change in eGFR; (iii) the change in CKD
      stage; and (iv) the presence of CKD upstaging. Regression models were used to
      determine the effect of surgical procedure (RN vs PN), access technique (open vs
      laparoscopic) and several preoperative characteristics on functional outcomes.
      RESULTS: In all, 276 patients met the inclusion criteria (174 RN and 102 PN) of
      whom 209 had a preoperative eGFR of >60 mL/min/1.73m(2). After >or=3 months from
      surgery, 108/209 (52%) patients developed new-onset eGFR of <60 mL/min/1.73m(2).
      On multivariate analysis, preoperative CKD stage (P < 0.001) and procedure (P=
      0.001) were both independent predictors of all four functional outcomes measured.
      Also, hypertension was an independent predictor of CKD upstaging (P= 0.02).
      Surgical access technique was not an independent predictor of any of the renal
      functional outcomes measured. CONCLUSION: Patients undergoing renal surgery have
      a high rate of new-onset CKD afterward. After controlling for preoperative risk
      factors, patients undergoing RN are at greater risk of a decline in renal
      function. However, surgical access technique was not a significant predictor for
      renal impairment.

PMID- 20039870
TI  - Glucose-regulated protein 78 expression in urothelial carcinoma of the upper
      urinary tract.
AB  - OBJECTIVE: To examine glucose-regulated protein 78 (GRP78; a major molecular
      chaperone at the endoplasmic reticulum, strongly expressed in several tumours)
      expression in urothelial carcinoma (UC) of the upper urinary tract (UUT) and to
      evaluate the diagnostic and progressive importance of GRP78 expression in UC-UUT.
      PATIENTS AND METHODS: We investigated GRP78 expression (using
      immunohistochemistry) in 126 UC-UUTs to assess its relevance to progression.
      GRP78 overexpression was recognised in 23 (18.3%) of tumour samples. RESULTS:
      There was no association between GRP78 overexpression and clinicopathological
      findings, except for an association with low grade in invasive tumours. GRP78
      overexpression significantly improved the disease-free survival rate in all
      patients (according to univariate and multivariate analyses), but did not alter
      the overall survival rate. CONCLUSION: The detection of GRP78 overexpression
      would appear to provide valuable information for the prognosis of UC-UUT.

PMID- 20039871
TI  - Interactions between inducible nitric oxide synthase and cyclooxygenase-2 in
      response to ischaemia-reperfusion of rabbit bladder.
AB  - OBJECTIVE: To investigate the interactions between inducible nitric oxide
      synthase (iNOS) and cyclooxygenase-2 (COX-2) in response to ischaemia-reperfusion
      (I/R) of rabbit bladder. MATERIALS AND METHODS: Rabbit bladders were exposed to 2
      h of ischaemia by bilaterally clamping the major arteries entering the bladder
      and then a subsequent 36 h of reperfusion (I/R) with or without intraperitoneal
      administration of a selective iNOS inhibitor n-(3-(amynomethyl)benzyl)acetamidine
      (1400W) or a selective COX-2 inhibitor NS-398 given 1 h before killing. The
      bladder tissues were processed for isometric tension experiments, enzymatic NOS
      activitiy, tissue contents of nitrite/nitrate (NO(X) ), cyclic guanosine
      monophosphate (cGMP) and COX activity determined by prostaglandin E(2) (PGE(2) )
      production. RESULTS: iNOS and constitutive NOS (cNOS) activities, NO(X) and
      PGE(2) contents in the bladder tissues at 36 h after reperfusion were
      significantly higher than those in the sham group with no significant increase in
      cGMP. Treatment with 1400W abrogated the increases in iNOS activity and NO(X) as
      well as PGE(2) without changing cNOS activity. In the tension experiments, a NOS
      substrate, l-arginine, induced detrusor contraction only in the I/R group, which
      was inhibited by 1400W or NS-398 but not by a selective soluble guanylate cyclase
      inhibitor 1H-[1,2,4] oxadiazole[4,3-a]quinoxalin-1-one (ODQ). 8-Br-cGMP induced
      detrusor relaxation in the sham and I/R groups. Also, l-arginine increased NO(X)
      and PGE(2) in the bladder tissues only in the I/R group, which were inhibited by
      pretreatment with 1400W. While, l-arginine increased cGMP contents in the I/R
      group and this increase was suppressed by ODQ but not by 1400W. CONCLUSION: These
      results show that NO derived from an up-regulation of iNOS after I/R increases
      COX-2-derived PG via a cGMP-independent mechanism. NO-mediated activation of COX
      2 may be an important mechanism for the modulation of bladder function after I/R
      injury.

PMID- 20039872
TI  - An interactive multimedia approach to urological anatomy.

PMID- 20039873
TI  - Progression from laparoscopic to robotic renal surgery: the next frontier.

PMID- 20039874
TI  - What controls polyspermy in mammals, the oviduct or the oocyte?
AB  - A block to polyspermy is required for successful fertilisation and embryo
      survival in mammals. A higher incidence of polyspermy is observed during in vitro
      fertilisation (IVF) compared with the in vivo situation in several species. Two
      groups of mechanisms have traditionally been proposed as contributing to the
      block to polyspermy in mammals: oviduct-based mechanisms, avoiding a massive
      arrival of spermatozoa in the proximity of the oocyte, and egg-based mechanisms,
      including changes in the membrane and zona pellucida (ZP) in reaction to the
      fertilising sperm. Additionally, a mechanism has been described recently which
      involves modifications of the ZP in the oviduct before the oocyte interacts with
      spermatozoa, termed "pre-fertilisation zona pellucida hardening". This mechanism
      is mediated by the oviductal-specific glycoprotein (OVGP1) secreted by the
      oviductal epithelial cells around the time of ovulation, and is reinforced by
      heparin-like glycosaminoglycans (S-GAGs) present in oviductal fluid.
      Identification of the molecules contributing to the ZP modifications in the
      oviduct will improve our knowledge of the mechanisms of sperm-egg interaction and
      could help to increase the success of IVF systems in domestic animals and humans.

PMID- 20039875
TI  - Gender-specific association of methylenetetrahydrofolate reductase genotype and
      haplotype with the aggressiveness and prognosis of clear cell renal cell
      carcinoma in Japanese patients.
AB  - OBJECTIVE: To determine if the two common polymorphisms in the
      methylenetetrahydrofolate reductase (MTHFR) gene, C677T and A1298C, affect tumour
      aggressiveness or prognosis of clear cell renal cell carcinoma (CCRCC) in
      Japanese patients. PATIENTS AND METHODS: MTHFR C677T and A1298C polymorphisms
      have been reported to cause decreased enzyme activity, which reduces the quantity
      of methyl groups available for DNA methylation and leads to mis-incorporation of
      uracil into DNA, resulting in single-strand DNA breaks. These effects might
      induce the accumulation of several genetic changes, leading to the development
      and progression of CCRCC. Therefore, we investigated the associations between
      MTHFR genotypes and haplotypes and the clinicopathological characteristics and
      survival rates in 240 Japanese patients with histopathologically confirmed CCRCC.
      MTHFR C677T and A1298C were genotyped and haplotypes were analysed using
      appropriate software. RESULTS: The variant genotypes of MTHFR A1298C were
      significantly associated with some advanced characteristics of CCRCC in all
      patients, and these associations were stronger among men. However, among women,
      the variant genotypes of MTHFR C677T were associated with some advanced
      characteristics of CCRCC and the C677T variant genotypes or the 677T-1298A
      haplotype was significantly associated with decreased overall survival (P = 0.007
      and P = 0.009, respectively). CONCLUSION: To our knowledge, this is the first
      report on the association between MTHFR polymorphisms and CCRCC aggressiveness or
      prognosis. These results suggest that the MTHFR genotypes and haplotype might be
      useful, in a gender-specific manner, as predictive factors for the clinical
      course of CCRCC. Furthermore, these findings will contribute to the understanding
      of the mechanisms underlying CCRCC progression.

PMID- 20039876
TI  - Blebbistatin inhibits contraction and accelerates migration in mouse hepatic
      stellate cells.
AB  - BACKGROUND AND PURPOSE: Blebbistatin, an inhibitor of myosin-II-specific ATPase,
      has been used to inhibit contraction of invertebrate and mammalian muscle
      preparations containing non-muscle myosin. Activated hepatic stellate cells have
      contractile properties and play an important role in the pathophysiology of liver
      fibrosis and portal hypertension. Therefore, hepatic stellate cells are
      considered as therapeutic target cells. In the present study, we studied the
      effect of blebbistatin during the transition of mouse hepatic stellate cells into
      contractile myofibroblasts. EXPERIMENTAL APPROACH: Effects of blebbistatin on
      cell morphology were evaluated by phase contrast microscopy. Cell stress fibres
      and focal adhesions were investigated by dual immunofluorescence staining and
      visualized using fluorescence microscopy. Contractile force generation was
      examined by silicone wrinkle formation assays and collagen gel contraction
      assays. Intracellular Ca(2+) release in response to endothelin-1 was measured by
      using Fluo-4. Cell migration was measured by wound healing experiments. KEY
      RESULTS: In culture-activated hepatic stellate cells, blebbistatin was found to
      change both cell morphology and function. In the presence of blebbistatin,
      stellate cells became smaller, acquired a dendritic morphology and had less
      myosin IIA-containing stress fibres and vinculin-containing focal adhesions.
      Moreover, blebbistatin impaired silicone wrinkle formation, reduced collagen gel
      contraction and blocked endothelin-1-induced intracellular Ca(2+) release.
      Finally, it promoted wound-induced cell migration. CONCLUSIONS AND IMPLICATIONS:
      By inhibiting myosin II ATPase, blebbistatin has profound effects on the
      morphology and function of activated hepatic stellate cells. Our data suggest
      that myosin II could be a therapeutic target in the treatment of liver fibrosis
      and portal hypertension.

PMID- 20039877
TI  - The chemokine-binding protein encoded by the poxvirus orf virus inhibits
      recruitment of dendritic cells to sites of skin inflammation and migration to
      peripheral lymph nodes.
AB  - Orf virus (ORFV) is a zoonotic parapoxvirus that induces acute pustular skin
      lesions in sheep and humans. ORFV can reinfect its host and the discovery of
      several secreted immune modulatory factors that include a chemokine-binding
      protein (CBP) may explain this phenomenon. Dendritic cells (DC) are professional
      antigen presenting cells that induce adaptive immunity and their recruitment to
      sites of infection in skin and migration to peripheral lymph nodes is critically
      dependent on inflammatory and constitutive chemokine gradients respectively. Here
      we examined whether ORFV-CBP could disable these gradients using mouse models.
      Previously we established that ORFV-CBP bound murine inflammatory chemokines with
      high affinity and here we show that this binding spectrum extends to constitutive
      chemokines CCL19 and CCL21. Using cell-based chemotaxis assays, ORFV-CBP
      inhibited the movement of both immature and mature DC in response to these
      inflammatory and constitutive chemokines respectively. Moreover in C57BL/6 mice,
      intradermally injected CBP potently inhibited the recruitment of blood-derived DC
      to lipopolysaccharide-induced sites of skin inflammation and inhibited the
      migration of ex vivo CpG-activated DC to inguinal lymph nodes. Finally we showed
      that ORFV-CBP completely inhibited T responsiveness in the inguinal lymph nodes
      using intradermally injected DC pulsed with ovalbumin peptide and transfused
      transgenic T cells.

PMID- 20039878
TI  - Penitentiary or penthouse condo: the tuberculous granuloma from the microbe's
      point of view.
AB  - Granuloma formation represents a pivotal point during human infection with
      Mycobacterium tuberculosis, for this structure may limit mycobacterial spread and
      prevent active disease, while at the same time allow for the survival and
      persistence of viable mycobacteria within the host. The current therapeutic
      regimens for treating tuberculosis disease have proven effective in developing
      countries. However, in countries with large populations, limited access to health
      care, and high incidence of HIV co-infection, tuberculosis disease continues to
      represent a major global health emergency. Particularly, the emergence of
      extensively and multi-drug-resistant forms of tuberculosis underscores the need
      develop new treatment strategies. Recent mechanistic studies have identified
      bacterial virulence mechanisms that subvert host responses and lead to an
      inappropriate upregulation of host factors such as tumour necrosis factor-alpha
      (TNF-alpha) and matrix metalloproteinases (MMPs). Paradoxically, then, part of
      the mycobacterial virulence programme may be to promote granuloma development and
      maturation. These observations suggest that together with appropriate anti
      microbials host-based therapeutics directed at TNF-alpha and MMP inhibition may
      counteract the microbial subterfuge, reduce the pro-granulomatous response, and
      offer an enhanced therapeutic effect. Host-directed therapy that alters the
      immune response may offer an alternative approach towards reducing treatment
      duration, the risk of anti-microbial resistance and improving patient outcome.

PMID- 20039879
TI  - EspM2 is a RhoA guanine nucleotide exchange factor.
AB  - We investigated how the type III secretion system WxxxE effectors EspM2 of
      enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and
      SifA of Salmonella enterica serovar Typhimurium, which is involved in
      intracellular survival, modulate Rho GTPases. We identified a direct interaction
      between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance
      Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine
      nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange
      in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none
      of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which
      surround the catalytic loop, affected the stability of EspM2. Substitution of
      Q124, located within the catalytic loop of EspM2, with alanine, greatly
      attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce
      stress fibres upon ectopic expression. These results suggest that binding of SifA
      to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase
      GEF.

PMID- 20039880
TI  - HIF-1alpha mediates the induction of IL-8 and VEGF expression on infection with
      Afa/Dr diffusely adhering E. coli and promotes EMT-like behaviour.
AB  - Microbes regulate a large panel of intracellular signalling events that can
      promote inflammation and/or enhance tumour progression. Indeed, it has been shown
      that infection of human intestinal cells with the Afa/Dr diffusely adhering E.
      coli C1845 strain induces expression of pro-angiogenic and pro-inflammatory
      genes. Here, we demonstrate that exposure of cryptic-like intestinal epithelial
      cells to C1845 bacteria induces HIF-1alpha protein levels. This effect depends on
      the binding of F1845 adhesin to the membrane-associated DAF receptor that
      initiates signalling cascades promoting translational mechanisms. Indeed,
      inhibition of MAPK and PI-3K decreases HIF-1alpha protein levels and blocks C1845
      induced phosphorylation of the ribosomal S6 protein. Using RNA interference we
      show that bacteria-induced HIF-1alpha regulates the expression of IL-8, VEGF and
      Twist1, thereby pointing to a role for HIF-1 in angiogenesis and inflammation. In
      addition, infection correlates with a loss of E-cadherin and cytokeratin 18 and a
      rise in fibronectin, suggesting that bacteria may induce an epithelial to
      mesenchymal transition-like phenotype. Since HIF-1alpha silencing results in
      reversion of bacteria-induced EMT markers, we speculate that HIF-1alpha plays a
      key role linking bacterial infection to angiogenesis, inflammation and some
      aspects of cancer initiation.

PMID- 20039882
TI  - The Plasmodium serine-type SERA proteases display distinct expression patterns
      and non-essential in vivo roles during life cycle progression of the malaria
      parasite.
AB  - Parasite proteases play key roles in several fundamental steps of the Plasmodium
      life cycle, including haemoglobin degradation, host cell invasion and parasite
      egress. Plasmodium exit from infected host cells appears to be mediated by a
      class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs).
      A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an
      atypical active site serine residue instead of a catalytic cysteine. Members of
      this SERAser subfamily are abundantly expressed in asexual blood stages,
      rendering them attractive drug and vaccine targets. In this study, we show by
      antibody localization and in vivo fluorescent tagging with the red fluorescent
      protein mCherry that the two P. berghei serine-type family members, PbSERA1 and
      PbSERA2, display differential expression towards the final stages of merozoite
      formation. Via targeted gene replacement, we generated single and double gene
      knockouts of the P. berghei SERAser genes. These loss-of-function lines
      progressed normally through the parasite life cycle, suggesting a specialized,
      non-vital role for serine-type SERAs in vivo. Parasites lacking PbSERAser showed
      increased expression of the cysteine-type PbSERA3. Compensatory mechanisms
      between distinct SERA subfamilies may thus explain the absence of phenotypical
      defect in SERAser disruptants, and challenge the suitability to develop potent
      antimalarial drugs based on specific inhibitors of Plasmodium serine-type SERAs.

PMID- 20039881
TI  - The innate immune molecule, NOD1, regulates direct killing of Helicobacter pylori
      by antimicrobial peptides.
AB  - The cytosolic innate immune molecule, NOD1, recognizes peptidoglycan (PG)
      delivered to epithelial cells via the Helicobacter pylori cag pathogenicity
      island (cagPAI), and has been implicated in host defence against cagPAI(+)H.
      pylori bacteria. To further clarify the role of NOD1 in host defence, we
      investigated NOD1-dependent regulation of human beta-defensins (DEFBs) in two
      epithelial cell lines. Our findings identify that NOD1 activation, via either
      cagPAI(+) bacteria or internalized PG, was required for DEFB4 and DEFB103
      expression in HEK293 cells. To investigate cell type-specific induction of DEFB4
      and DEFB103, we generated stable NOD1'knockdown' (KD) and control AGS cells.
      Reporter gene assay and RT-PCR analyses revealed that only DEFB4 was induced in
      an NOD1-/cagPAI-dependent fashion in AGS cells. Moreover, culture supernatants
      from AGS control, but not AGS NOD1 KD cells, stimulated with cagPAI(+)H. pylori,
      significantly reduced H. pylori bacterial numbers. siRNA studies confirmed that
      human beta-defensin 2 (hBD-2), but not hBD-3, contributes to the antimicrobial
      activity of AGS cell supernatants against H. pylori. This study demonstrates, for
      the first time, the involvement of NOD1 and hBD-2 in direct killing of H. pylori
      bacteria by epithelial cells and confirms the importance of NOD1 in host defence
      mechanisms against cagPAI(+)H. pylori infection.

PMID- 20039884
TI  - Critical appraisal of a randomized trial: surgery is superior to octreotide LAR
      in newly diagnosed patients with acromegaly.

PMID- 20039885
TI  - d3-GHR genotype does not explain heterogeneity in GH responsiveness in
      hypopituitary adults.
AB  - OBJECTIVE: Heterogeneity in growth hormone (GH) responsiveness in adult
      hypopituitary patients receiving recombinant human GH (rhGH) is poorly
      understood; doses vary up to fourfold between individuals. Deletion of exon 3 in
      the GH receptor (d3-GHR) has been linked to enhanced rhGH responsiveness in
      children. We investigated the role of the d3-GHR polymorphism in determining
      adult rhGH responsiveness. METHODS: One hundred and ninety-four patients treated
      with an identical rhGH dosing protocol in a single centre were genotyped for the
      d3-GHR, and the results correlated with changes in serum IGF-I and clinical
      parameters of GH responsiveness after 6 and 12 months of GH replacement therapy.
      RESULTS: Allele frequencies for homozygous full length (fl/fl), heterozygous d3
      (fl/d3) and homozygous d3 (d3/d3) were 52%, 38.7% and 9.3%, respectively, and
      were in Hardy-Weinberg equilibrium. Baseline IGF-I and DeltaIGF-I at 6 months
      were comparable between groups. DeltaIGF-I at 12 months was significantly greater
      in the d3/d3 group (P = 0.028). No difference was detected between fl/d3 and
      fl/fl groups. Regression analyses of DeltaIGF-I at 12 months and DeltaIGF-I/rhGH
      dose confirmed a significant relationship of d3/d3 genotype on rhGH response.
      There was no difference between groups in maintenance rhGH dose between
      genotypes. CONCLUSION: Homozygosity for d3-GHR confers a marginal increase in GH
      responsiveness at 12 months but without a detectable change in maintenance rhGH
      dose required. Both d3 alleles are required to achieve this response; given that
      only 10% of the population are d3 homozygotes, the d3GHR does not explain the
      marked heterogeneity of GH responsiveness in hypopituitary adults.

PMID- 20039886
TI  - Cerebral cavernoma: an emerging long-term consequence of external beam radiation
      in childhood.
AB  - The long-term effects of cranial external beam radiotherapy are emerging as
      survival rates for cerebral tumours improve. Cerebral cavernoma are a recognized
      consequence of cranial irradiation. Endocrinologists managing the life-long
      complications of hypopituitarism associated with irradiation need to be aware and
      vigilant of the risks of cavernoma formation, in particular in the population
      with a history of childhood irradiation. We present three cases of young patients
      who were diagnosed with cerebral cavernoma many years after childhood irradiation
      treatment and review the current literature on this condition. We discuss
      implications for endocrine practice as rising numbers of patients survive
      childhood cancer and irradiation and are now attending adult endocrine services
      for long-term management of secondary hypopituitarism.

PMID- 20039887
TI  - Increased mortality and morbidity in mild primary hyperparathyroid patients. The
      Parathyroid Epidemiology and Audit Research Study (PEARS).
AB  - OBJECTIVE: To describe mortality and disease-specific morbidities in patients
      with mild primary hyperparathyroidism (PHPT). DESIGN: Retrospective population
      based observational study. SETTING: Tayside, Scotland, from 1997 to 2006.
      PARTICIPANTS: Patients with mild PHPT were selected from a predefined PHPT cohort
      between 1997 and 2006. MAIN OUTCOME MEASURES: Standardised mortality ratios
      (SMRs) were examined for all-cause mortality, as well as cardiovascular and
      cancer mortality. Standardised morbidity ratios and standardised incidence ratios
      were also calculated for eleven observed co-morbidities. RESULTS: In total, there
      were 1683 (69.1% female) patients identified with mild PHPT in Tayside. Patients
      were found to have an increased risk of all-cause mortality and cardiovascular
      mortality (SMR-all cause 2.62, 95% CI 2.39-2.86; SMR-cardiovascular 2.68, 95% CI
      2.34-3.05). Patients with mild PHPT had a significantly increased risk of
      developing cardiovascular and cerebrovascular disease, renal dysfunction and
      fractures compared to the age- and sex-adjusted general population. CONCLUSIONS:
      Mortality and morbidity were increased for patients with mild untreated PHPT,
      which is similar to more severe PHPT.

PMID- 20039888
TI  - How reliably can autoimmune hypophysitis be diagnosed without pituitary biopsy.
AB  - Autoimmune hypophysitis is a rare chronic inflammatory condition of the pituitary
      gland which typically presents with hypopituitarism and a pituitary mass. Cases
      involving anterior pituitary alone (65%) are six times more common in women,
      typically presenting during pregnancy or postpartum (57%). Anterior and posterior
      pituitary involvement (25%) are twice as common in women, and neurohypophysis
      alone (10%) occurs equally in both sexes. It has a prevalence of around 5 per
      million, an annual incidence of 1 in 7 to 9 million and in our experience
      represents the known or suspected cause of 0.5% of cases of hypopituitarism, <1%
      of pituitary masses and 2% of nonfunctioning macro lesions presenting to an
      endocrine clinic. However, 'missed' cases of autoimmune hypophysitis may be the
      aetiology of some other unexplained cases of hypopituitarism. Clinically,
      headache and visual disturbance are common. Anterior hypopituitarism shows a
      characteristic but atypical pattern of deficiency of ACTH followed by TSH,
      gonadotrophins and prolactin deficiency or hyperprolactinaemia. Eighteen percent
      of cases have evidence of another autoimmune condition. On magnetic resonance
      imaging (MRI), autoimmune hypophysitis is typically symmetrical and homogeneous
      with thickened but undisplaced stalk in contrast to typical findings with
      pituitary tumours. Ultimately, the histological diagnosis of autoimmune
      hypophysitis can only be confirmed by surgery but a presumptive diagnosis can
      often be made on the basis of a combination of context and clinical features, and
      pituitary biopsy is not always clinically necessary for effective clinical
      management of the patient.

PMID- 20039890
TI  - Successful therapy of Cushing's disease caused by an extrapituitary parasellar
      adenoma.

PMID- 20039889
TI  - The effect of DPP-4 inhibition with sitagliptin on incretin secretion and on
      fasting and postprandial glucose turnover in subjects with impaired fasting
      glucose.
AB  - OBJECTIVE: Low glucagon-like peptide-1 (GLP-1) concentrations have been observed
      in impaired fasting glucose (IFG). It is uncertain whether these abnormalities
      contribute directly to the pathogenesis of IFG and impaired glucose tolerance.
      Dipeptidyl peptidase-4 (DPP-4) inhibitors raise incretin hormone concentrations
      enabling an examination of their effects on glucose turnover in IFG. RESEARCH
      DESIGN AND METHODS: We studied 22 subjects with IFG using a double-blinded,
      placebo-controlled, parallel-group design. At the time of enrollment, subjects
      ate a standardized meal labelled with [1-(13)C]-glucose. Infused [6-(3)H] glucose
      enabled measurement of systemic meal appearance (MRa). Infused [6,6-(2)H(2)]
      glucose enabled measurement of endogenous glucose production (EGP) and glucose
      disappearance (Rd). Subsequently, subjects were randomized to 100 mg of
      sitagliptin daily or placebo. After an 8-week treatment period, the mixed meal
      was repeated. RESULTS: As expected, subjects with IFG who received placebo did
      not experience any change in glucose concentrations. Despite raising intact GLP-1
      concentrations, treatment with sitagliptin did not alter either fasting or
      postprandial glucose, insulin or C-peptide concentrations. Postprandial EGP (18.1
      +/- 0.7 vs 17.6 +/- 0.8 micromol/kg per min, P = 0.53), Rd (55.6 +/- 4.3 vs 58.9
      +/- 3.3 micromol/kg per min, P = 0.47) and MRa (6639 +/- 377 vs 6581 +/- 316
      micromol/kg per 6 h, P = 0.85) were unchanged. Sitagliptin was associated with
      decreased total GLP-1 implying decreased incretin secretion. CONCLUSIONS: DPP-4
      inhibition did not alter fasting or postprandial glucose turnover in people with
      IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis
      of IFG.

PMID- 20039891
TI  - Failure of rituximab treatment in a case of severe thyroid ophthalmopathy
      unresponsive to steroids.

PMID- 20039892
TI  - Influence of various confounding variables and storage conditions on metanephrine
      and normetanephrine levels in plasma.
AB  - OBJECTIVE: Measurements of plasma free metanephrines have been advocated as first
      line tests for phaeochromocytoma. The aim of the study was to assess the impact
      of potential confounding variables. DESIGN: Comparative study between 2008 and
      2009. SUBJECTS: Hundred and eighty healthy subjects. MEASUREMENTS: The effects of
      age, BMI, gender, menstrual cycle (sampling every 2 days), time of day (sampling
      every 2 h), venepunture (0, 15, 30, 60, 90 and 120 min), physical exercise (0, 15
      and 30 min), coffee (0 and 60 min), breakfast (0 and 60 min) and various body
      positions (standing and supine rest, each 0 and 120 min) were evaluated. In
      addition, whole blood and plasma samples were stored at 4 degrees C or at 22
      degrees C for 0, 1, 3, 24 and 72 h. Plasma free metanephrines were measured using
      radioimmunoassay (LDN). RESULTS: While metanephrine was significantly influenced
      by sex and age, BMI and sex were significant predictors of normetanephrine.
      Coffee (+20%) and food (+8%) elevated normetanephrine significantly (P < 0.05),
      while metanephrine remained stable. Physical exercise increased metanephrine
      (+82%) as well as normetanephrine (+84%) significantly (P < 0.005). Supine rest
      significantly decreased both metanephrine (-34%) and normetanephrine (-19%) when
      compared to standing rest (P < 0.01). Metanephrine and normetanephrine were not
      significantly influenced by time of day, menstrual cycle or venepuncture. When
      plasma samples were stored at 4 degrees C, metanephrine and normetanephrine were
      stable for 72 h. CONCLUSIONS: Physical exercise may lead to relevant changes in
      metanephrine and normetanephrine and should therefore be avoided prior to
      sampling. Although effects of age, sex and BMI were small, these variables should
      be considered when interpreting biochemical results. Blood should be taken in the
      supine position, and samples should be immediately centrifuged and stored at 4
      degrees C to improve stability.

PMID- 20039893
TI  - The metabolic syndrome is associated with subclinical atherosclerosis independent
      of insulin resistance: the Guangzhou Biobank Cohort Study-CVD.
AB  - OBJECTIVE: We examined whether the association of the metabolic syndrome (MetS)
      and subclinical atherosclerosis is independent of insulin resistance in a Chinese
      community sample with no history of type 2 diabetes. METHODS: Five hundred and
      ninety-six men and 526 women from a substudy of the Guangzhou Biobank Cohort
      Study (GBCS-CVD) had carotid intimal-medial thickness (IMT) measured by B-mode
      ultrasonography, and brachial-ankle pulse wave velocity (PWV) and ankle-brachial
      systolic blood pressure index (ABI) measured simultaneously by a noninvasive
      automatic waveform analyser. RESULTS: Fourteen percentage had MetS as defined by
      the International Diabetes Federation. Obesity indices, systolic and diastolic
      blood pressure and pulse pressure, lipids, fasting and postload glucose and
      insulin, homeostatic model assessment of insulin resistance, glycosylated
      haemoglobin A1c, leptin, high-sensitivity C-reactive protein, IMT and PWV
      increased and high-density lipoprotein-cholesterol, adiponectin and ABI decreased
      significantly with increasing number of MetS components after adjusting for age
      and sex (P for trend from 0.004 to <0.001). After adjusting for traditional
      cardiovascular risk factors and insulin resistance, the odds ratios [OR (95% CI)]
      of thicker IMT (> or =1.0 mm), higher PWV (> or =14.0 m/s) and low ABI (< or
      =1.0) for MetS were significantly increased [2.28 (1.19-4.38), 2.17 (1.36-3.46)
      and 1.72 (1.14-2.59), respectively, all P < 0.01] but were lower than the
      adjusted OR for those with three or more MetS components. CONCLUSION: MetS was
      associated with subclinical atherosclerosis independent of insulin resistance.
      The presence of increasing number of MetS risk factors appeared to be more
      important than the diagnosis of MetS in predicting subclinical atherosclerosis.
      Early screening for MetS risk factors might identify those at greater
      cardiovascular risk.

PMID- 20039894
TI  - Predictive value of pentagastrin test for preoperative differential diagnosis
      between C-cell hyperplasia and medullary thyroid carcinoma in patients with
      moderately elevated basal calcitonin levels.
AB  - BACKGROUND AND OBJECTIVES: Medullary thyroid carcinoma (MTC) is a calcitonin (CT)
      secreting neuroendocrine tumour originating from thyroid C cells. Serum CT
      concentrations are helpful in the early detection of MTC, while it is still
      unclear whether they can be used also for the differential diagnosis between MTC
      and C-cell hyperplasia (CCH), a precancerous condition in familial MTCs but with
      unclear clinical significance in sporadic MTCs. Nowadays, surgery is recommended
      in all patients with basal or pentagastrin (PG)-stimulated CT value of 100 pg/ml
      or more, without discriminating if they are affected with MTC or CCH only. The
      objective of this study was to investigate the utility of the PG test for CT in
      distinguishing CCH from MTC before surgery. PATIENTS AND METHODS: Sixteen of 20
      patients with thyroid nodules and basal CT levels between 15 and 100 ng/l had a
      positive PG test (>100 ng/l PG CT peak) and form the basis of the data analysis.
      A diagnosis of MTC was histologically proved on surgical samples in seven
      patients and of CCH in nine other patients. Four patients with neither FNAB nor
      PG test consistent with a diagnosis of MTC did not undergo thyroidectomy.
      RESULTS: A peak of CT of 275 ng/l after PG was able to significantly distinguish
      patients with MTC from patients with CCH, with 100% sensitivity and 89%
      specificity (P = 0.002). PG-stimulated calcitonin levels >275 ng/l had a positive
      predictive value (PPV) value for diagnosis of MTC of 100%, and PG-stimulated
      calcitonin levels <275 had a PPV for the diagnosis of CCH of 89%. CONCLUSIONS: A
      CT cut-off after PG of 275 ng/l is suggested to be highly predictive in
      distinguishing CCH from MTC before surgery, and this may be helpful in selecting
      patients for thyroid surgery.

PMID- 20039895
TI  - Influence of physiological dietary selenium supplementation on the natural course
      of autoimmune thyroiditis.
AB  - OBJECTIVE: Our study aimed to investigate whether physiological doses of selenium
      (Se) influence the natural course of autoimmune thyroiditis (AIT). DESIGN AND
      PATIENTS: A total of 76 consecutive patients (65 F, 11 M, median 43, range 15-75
      years) with AIT, normal or slightly elevated TSH and fT4 within the normal range
      were divided into two groups: Group 0 (30 cases) was given no treatment while
      Group 1 (46 cases) was treated with sodium selenite 80 MUg/day as a single oral
      dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO-Ab; Tg
      Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and
      after 6 and 12 months of follow-up. Thyroid ultrasonography (US) was performed at
      each follow-up point. Echogenicity was measured by histographic analysis of gray
      scale pixels (gsp) ranging from 0 = black to 255 = white. RESULTS: Thyroid
      echogenicity decreased significantly in both groups after 6 months, but after 12
      months, it had changed no more in Group 1, whereas it had dropped further in
      Group 0. No significant variation in TPO-Ab or Tg-Ab levels was observed between
      the two groups after 6 months, but both values decreased significantly after 12
      months in Group 1, and five patients in this group became negative for TPO-Ab.
      TSH and FT4 showed no significant variations in either group. CONCLUSIONS:
      Dietary supplementation with physiological doses of Se seems to be effective in
      preventing a reduction in thyroid echogenicity after 6 months of treatment and in
      reducing TPO-Ab and Tg-Ab after 12 months, but does not modify TSH or FT4.

PMID- 20039897
TI  - The 4-mg intravenous dexamethasone suppression test in the diagnosis of Cushing's
      syndrome.
AB  - OBJECTIVE: Optimal diagnostic criteria for the 4-mg intravenous dexamethasone
      suppression test (IVDST) in patients with Cushing's syndrome (CS), compared with
      normal subjects, have not been established. We evaluated the performance of the 4
      mg IVDST for differentiating CS from normal subjects and to define the responses
      in CS of various aetiologies. DESIGN, SUBJECTS, MEASUREMENTS: Thirty-two control
      subjects [normal and overweight/obese participants with or without type 2
      diabetes) were prospectively studied, and data from 66 patients with Cushing's
      disease (CD), three with ectopic ACTH syndrome (EAS), 14 with adrenal Cushing's
      (AC)] and 15 with low probability of CS (LPC) from three tertiary hospitals were
      retrospectively evaluated. Dexamethasone was infused at 1 mg/h for 4 h. Plasma
      cortisol and ACTH were measured at -60 min (baseline), -5 min, +3 h, +4 h, +5 h
      and at +23 and +23.5 h on Day 2. RESULTS: Control subjects (including those with
      type 2 diabetes) exhibited a marked suppression of cortisol which was maintained
      until Day 2. Two of 15 patients with LPC had Day 2 cortisol results that
      overlapped with CS. Patients with CD demonstrated partial suppression, with
      rebound hypercortisolism on Day 2. Patients with AC and EAS did not suppress
      cortisol levels. Day 2 cortisol level of >130 nmol/l (or >20% of the baseline)
      diagnosed CS with 100% sensitivity and 96% specificity. CONCLUSION: While the
      IVDST allowed complete discrimination between control subjects and CS, 13% of LPC
      overlapped with CS. Given the small number of EAS, no conclusion can be drawn
      regarding the utility of this test in the differential diagnosis of CS.

PMID- 20039896
TI  - A novel de novo germ-line V292M mutation in the extracellular region of RET in a
      patient with phaeochromocytoma and medullary thyroid carcinoma: functional
      characterization.
AB  - CONTEXT: In multiple endocrine neoplasia (MEN), rearranged during transfection
      (RET), gene testing has been extensively exploited to characterize tumour
      aggressiveness and optimize the diagnostic and clinical management. OBJECTIVE: To
      report the underlying genetic alterations in an unusual case of MEN type 2 (MEN
      2A). DESIGN AND PATIENT: Occult medullary thyroid carcinoma (MTC) was diagnosed
      in a 44-year-old man who had presented with unilateral phaeochromcytoma. DNA
      extracted from the blood and tumour tissues was analysed for mutations in RET.
      The transforming potential and mitogenic properties of the identified RET
      mutation were investigated. RESULTS: The patient carried a novel heterozygous
      germ-line RET mutation in exon 5 (Val292Met, GTG>ATG) (V292M/RET) with no
      evidence of additional somatic alterations. The mutation maps to the third
      cadherin-like domain of RET, which is usually not included in RET screening.
      Interestingly, MTC with concomitant phaeochromcytoma has never been associated
      with a RET mutation involving the extracellular cadherin-like domain. V292M/RET
      was absent in the only two relatives examined. In vitro assays indicate that the
      mutant has low-grade transforming potential. CONCLUSIONS: Complete
      characterization and classification of all novel RET mutations are essential for
      extending genetic analysis in clinical practice. Our findings suggest that: (i)
      in all MEN-2 patients negative for RET hot-spot mutations, testing should be
      extended to all coding regions of the gene and (ii) the newly identified
      V292M/RET mutation is characterized by relatively weak in vitro transforming
      ability.

PMID- 20039900
TI  - The cardiac calsequestrin gene (CASQ2) is up-regulated in the thyroid in patients
      with Graves' ophthalmopathy--support for a role of autoimmunity against
      calsequestrin as the triggering event.
AB  - BACKGROUND: Graves' Ophthalmopathy (GO) is a complex eye and orbital disorder
      that is uniquely linked to Graves' Hyperthyroidism (GH) and has traditionally
      been considered a cross-reactive immune response against the thyroid stimulating
      hormone receptor (TSHR) in orbital tissue. However, because there is no direct
      evidence, such as specific TSHR antibodies or T lymphocytes targeting the orbital
      tissues in patients with GO compared to those without eye disease, it is
      important to consider alternative hypotheses for the pathogenesis of GO. The aim
      of this study was to identify differentially expressed genes within the thyroid
      of patients with GO and GH as a possible explanation for a thyroid initiated
      orbital autoimmunity. METHODS: RNA was extracted from thyroid glands of patients
      with GO (n = 10) and GH (n = 8) post-total thyroidectomy. RNA samples were
      arrayed on Illumina(r) Human Ref-8 Expression BeadChipsTM representing 20,589
      genes. Microarray results of selected genes were validated by quantitative PCR
      (qPCR) and levels of protein translation measured by Western blot analysis.
      FINDINGS: Two hundred and ninety-five genes were differentially expressed between
      patients with GO and GH. Of these, the cardiac calsequestrin gene (CASQ2) was the
      most highly expressed gene in GO (2.2-fold increase, P < 0.05). The succinate
      dehydrogenase flavoprotein subunit gene (SDHA) was also significantly up
      regulated in GO (P < 0.05), 1.4-fold, while genes encoding the thyroid antigens
      thyroglobulin, thyroid peroxidase and TSHR were not differentially expressed.
      qPCR verified up-regulation of CASQ2 and down-regulation BMP7, CD80, IGFBP5, and
      MYD88 genes in GO. Western blot analysis showed that the average CASQ/GAPDH
      protein expression ratios for GH and GO were 1.04 and 1.03, respectively. t-Test
      analysis of data generated a P-value of 0.26, therefore no significant difference
      was found for CASQ protein expression in thyroid tissue between GH and GO.
      INTERPRETATION: The skeletal and cardiac calsequestrin proteins share 68.4% amino
      acid homology. Previous work has shown that RNA levels of skeletal muscle
      calsequestrin are 4.7 times higher in extraocular muscle (EOM) than in
      masticatory skeletal muscle (jaw), and cardiac calsequestrin is expressed 2.7
      times more in EOM. We postulate that up-regulation of casq2 gene in the thyroid
      of patients with GH may lead to the production of autoantibodies and sensitized T
      lymphocytes, which cross-react with calsequestrin in the EOM of patients who
      develop ophthalmopathy.

PMID- 20039898
TI  - Outcome of fractionated stereotactic radiotherapy in patients with pituitary
      adenomas resistant to conventional treatments: a 5.25-year follow-up study.
AB  - OBJECTIVE: To investigate the long-term outcome of fractionated stereotactic
      radiotherapy (FSRT) [45 Gy (range 45-54) in 25 fractions] in patients with
      pituitary adenomas characterized by tumour progression or hormonally active
      disease despite surgery and/or medical therapy. DESIGN: This was an observational
      follow-up study of 5.25 years (median; range 1.7-10.4). PATIENTS AND
      MEASUREMENTS: Pituitary tumour volume, visual acuity/fields, hypersecretion,
      hypopituitarism, cerebrovascular disease, second brain tumours and mortality were
      examined at regular intervals after FSRT in 30 patients with pituitary adenomas
      (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been
      operated 1-3 times, 47% had visual field deficits/impaired vision and 50%
      pituitary dysfunction. Progressive disease, stable disease, partial and complete
      tumour response were defined by MRI. RESULTS: Tumour growth control was 100%. At
      the end of follow-up, 30% had stable disease, 60% partial and 10% complete tumour
      response. Visual function was preserved and 36% of patients with prior field
      deficits improved. GH decreased from 4.2 (range, 2.3-6.5) to 1.1 (range, 0.5-1.5)
      microg/l (P < 0.001) in patients with acromegaly, and medical therapy could be
      reduced. In large prolactinomas, partial response or complete tumour response was
      achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33%
      of patients had stable dysfunction, 17% deteriorated further and 23% developed
      new dysfunction. There were no cerebrovascular events, second brain tumours or
      FSRT-related deaths. CONCLUSION: According to this long-term follow-up study,
      FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory
      to conventional treatments.

PMID- 20039899
TI  - Partial growth hormone deficiency is associated with an adverse cardiovascular
      risk profile and increased carotid intima-medial thickness.
AB  - OBJECTIVE: To quantify the relative prevalence of surrogate markers of vascular
      risk in adults with partial GH deficiency (GH insufficiency, GHI). CONTEXT:
      Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular
      mortality and demonstrate clustering of adverse vascular risk factors. The
      vascular risk profile of GHI adults has yet to be comprehensively studied.
      DESIGN: A cross-sectional case controlled study. PATIENTS: Thirty GHD adults, 24
      GHI, and 30 age- and sex-matched controls. GHI adults were defined biochemically
      using two GH stimulation tests (peak GH 3-7 MUg/l). MEASUREMENTS: Serum lipids
      and apolipoproteins, plasminogen activator inhibitor type-I (PAI-I), C-reactive
      protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid
      intima-medial thickness (IMT). RESULTS: IGF-I levels of GHI adults were lower
      than controls (373 +/- 123 vs 295 +/- 104 MUg/l; P < 0.001). Total cholesterol
      (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) values
      were consistently between those of, but not significantly different from, GHD and
      control subjects. GHI adults showed significantly elevated PAI-I levels [80 (13
      98) vs 50.5 (3-98) ng/ml; P = 0.01], although no there were differences in CRP,
      Lp(a), and fibrinogen levels compared with control subjects. No differences in
      systolic or diastolic blood pressure were shown between study groups. In parallel
      with the increased vascular risk profile of GH-insufficient adults, carotid IMT
      was significantly increased (0.503 +/- 0.08 vs 0.578 +/- 0.130 mm; P = 0.02). TC,
      LDL-C, Waist-Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF-I
      levels and GH status. TG, K(ITT), and PAI-I additionally correlated with GH
      status, but not with IGF-I levels. CONCLUSION: GHI adults are at elevated
      vascular risk, reflected by adverse surrogate markers and increased carotid IMT.
      The surrogate risk marker profile parallels GHD adults, but is less divergent
      from that observed in healthy individuals. No data are yet available as to
      whether these anomalies will be reflected in an increased vascular mortality in
      GHI adults.

PMID- 20039901
TI  - Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma.
AB  - OBJECTIVE: Although the strong association between hyperprolactinaemia and
      platelet aggregation is well recognized, there are no studies on changes in
      coagulation and fibrinolytic status in patients with prolactinoma. To our
      knowledge, tissue plasminogen activator inhibitor-1 (PAI-1), plasma tissue factor
      pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI)
      levels in these patients have not been investigated. Therefore, the main purpose
      of this study was to evaluate the markers of endogenous coagulation/fibrinolysis,
      including TFPI and TAFI, and to investigate the relationships between prolactin
      (PRL) and these haemostatic parameters and serum lipid profile in patients with
      prolactinoma. RESEARCH METHODS AND PROCEDURES: Twenty-two patients with
      untreated, newly diagnosed prolactinoma and 20 age-matched healthy controls were
      included in the study. Platelet count, mean platelet volume, prothrombin time,
      activated partial thromboplastin time, fibrinogen, factors V, VII, VIII, IX and X
      activities, von Willebrand factor, antithrombin III (AT-III), protein C, protein
      S, tissue plasminogen activator (t-PA), PAI-1, TFPI and TAFI, as well as common
      lipid variables, were measured. The relationships between serum PRL and these
      haemostatic parameters were evaluated. RESULTS: Compared with the control
      subjects, total cholesterol, low density lipoprotein cholesterol, apolipoprotein
      B, platelet count, fibrinogen, AT-III, PAI-1 and PAI-1/t-PA ratio were
      significantly increased in patients with prolactinoma (P < 0.0001, P < 0.001, P <
      0.05, P < 0.05, P < 0.0001, P < 0.05, P < 0.0001 and P < 0.0001, respectively),
      whereas TFPI levels were significantly decreased (P < 0.01). Plasma TAFI Ag
      levels were not significantly different in patients with prolactinoma compared
      with the controls. In patients with prolactinoma, serum PRL was positively
      correlated with plasma FVII levels and apo B (r: 0.679, P < 0.05; r: 0.548, P <
      0.05, respectively). CONCLUSION: We found some important differences in the
      haemostatic parameters between the patients with prolactinoma and healthy
      controls. Increased platelet count, fibrinogen, PAI-1 and decreased TFPI in
      patients with prolactinoma may represent a potential hypercoagulable and
      hypofibrinolytic state, which might augment the risk for atherosclerotic and
      atherothrombotic complications. Thus, disturbances of the haemostatic system and
      dyslipidaemia may lead to the excess mortality in patients with prolactinoma.

PMID- 20039902
TI  - Immune function in hypopituitarism: time to reconsider?
AB  - Hypopituitarism is not currently considered as a potential cause of immune
      disruption in humans. Accumulating data from in vitro and animal models support a
      role for the pituitary gland in immune regulation. Furthermore, the increased
      mortality risk noted in patients with adult hypopituitarism remains poorly
      explained and immune dysfunction could conceivably contribute to this
      observation. In a recent issue of Clinical & Experimental Immunology, we
      presented new data relating to immune status in adults with treated, severe
      hypopituitarism. We observed humoral immune deficiency in a significant
      proportion, despite stable pituitary replacement, including growth hormone (GH).
      This was especially evident in those with low pretreatment IGF-I levels and
      appeared independent of anticonvulsant use or corticosteroid replacement. These
      observations require substantiation with future studies. In this short review, we
      summarize existing data relating to the effects of pituitary hormones on immune
      function and discuss potential clinical implications surrounding the hypothesis
      of immune dysregulation in severe hypopituitarism.

PMID- 20039914
TI  - Use of reflectance confocal microscopy to monitor response of lentigo maligna to
      nonsurgical treatment.

PMID- 20039915
TI  - Crescent versus rectangle: is it a true negative margin in second and subsequent
      stages of Mohs surgery?
AB  - BACKGROUND: The hallmark of Mohs micrographic surgery is using tangential tissue
      sections that theoretically allow 100% of the tissue margin to be examined, but
      when taking additional layers for second and subsequent Mohs stages, no detailed
      methods have been described to ensure that 100% of the tissue margins are
      analyzed. METHOD: A rectangular or a crescent-shaped layer is often used to take
      second and subsequent stages. Here we compare the two techniques for their
      theoretic advantages and disadvantages. SUMMARY: The advantage of the rectangular
      shape has been ease of processing, as well as built in vertical "nicks" that
      automatically mark the border of the tissue removed, but the rectangular layer
      may not provide 100% evaluation of the tumor margin because the vertical edges of
      the rectangular layer are not always completely analyzed, and thus tumor cells
      cannot be visualized in the vertical margins of these layers. This might result
      in a false-negative margin reading, which can be avoided by using the crescent
      layer. CONCLUSION: We propose taking second and subsequent Mohs layers with only
      a crescent shape, which allows true 100% tissue margin assessment.

PMID- 20039916
TI  - Combined therapy for mycetoma: medical and surgical.

PMID- 20039918
TI  - Hidradenitis suppurativa: successful treatment using carbon dioxide laser
      excision and marsupialization.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a disease associated with
      significant patient morbidity and less-than-ideal therapies. OBJECTIVES: To
      determine the long- and short-term benefits of carbon dioxide (CO(2)) laser
      excision and marsupialization in the management of persisent lesions of HS.
      METHODS: Patients with long-standing lesions of HS were treated using a CO(2)
      laser to excise inflammatory and draining masses. RESULTS: One hundred eighty
      five areas were treated in 61 patients using the CO(2) laser excision and
      marsupialization technique in 154 sessions. Local anesthesia was used for all but
      three sessions. Healing occurred primarily through secondary intention. In follow
      up from 1 to 19 years, acceptable to excellent qualities of healing occurred.
      Recurrence within the treated area occurred in two of 185 sites treated.
      CONCLUSION: CO(2) laser excision and marsupialization appears to be an effective
      therapy for management of persisent or late-stage HS. There was good patient
      comfort during and after treatment, lower costs than with inpatient modalities,
      good healing, and minimal risk of recurrence within the treated areas.

PMID- 20039917
TI  - Chemosurgery for invasive melanoma.

PMID- 20039919
TI  - The value of preoperative biopsy-site photography for identifying cutaneous
      lesions.
AB  - BACKGROUND: Dermatologic surgeons rely on several methods to identify surgical
      sites (patients and their spouses, diagrams of surgical sites, gauze
      dermabrasion, biopsy-site scars, and referring physician identification), but it
      is not uncommon for several weeks to pass before surgery, allowing biopsy sites
      to become inconspicuous with healing. Practicing in a culture in which medical
      lawsuits continue to soar, it is prudent for dermatologists and dermatologic
      surgeons to locate surgical sites precisely using the most accurate and
      irrefutable means to protect themselves against costly lawsuits. OBJECTIVES: To
      determine the value of preoperative biopsy-site photography in accurately
      identifying surgical sites before Mohs micrographic surgery. METHODS: Two hundred
      seventy-one surgical sites were evaluated in the study. Patients with
      preoperative biopsy-site photography of cutaneous malignancies undergoing Mohs
      micrographic surgery were enrolled in the study. The day of the surgery, patients
      and physicians were asked to identify the surgical sites. RESULTS: The patient
      incorrectly identified 45 of 271 surgical sites (16.6%), and the physician
      incorrectly identified 16 of 271 surgical sites (5.9%). The surgeon and the
      patient both incorrectly identified 12 of 271 sites (4.4%). All surgical sites
      were correctly identified with preoperative biopsy-site photography.

PMID- 20039921
TI  - The chin and adjacent fat compartments.
AB  - BACKGROUND: The human face contains numerous subcutaneous compartments of fatty
      tissue, but neither a chin compartment nor a submental compartment have been
      described. Definitions of the jowl compartment vary considerably. OBJECTIVES: To
      investigate the borders between the subcutaneous fat compartments of the chin,
      submental region, and jowls. METHODS AND MATERIALS: Colored gelatin was injected
      into the subcutaneous tissues directly under the skin of 30 human cadaver heads.
      Macroscopic dissection was performed. RESULTS: Distinct chin and submental
      compartments were identified in all cases. The chin compartment is demarcated by
      the mentolabial groove superiorly, the submental ligaments inferiorly, and the
      labiomandibular grooves laterally. The submental compartment is demarcated from
      the chin by the submental ligaments, laterally by the paramedian platysma
      retaining ligaments, and inferiorly by the hyoid ligament. The upper border of
      the jowl compartment is formed by the mandibular ligaments and the platysma
      mandibular ligaments, the anterior border by the paramedian platysma-retaining
      ligaments, and the dorsal boundary by the submandibular platysma retaining
      ligaments. CONCLUSION: The chin compartment is well demarcated from adjacent
      compartments. The limits of the submental compartment vary. The jowl compartment
      is clearly demarcated from adjacent compartments.

PMID- 20039924
TI  - Cosmetic use of poly-l-lactic acid: a retrospective study of 130 patients.
AB  - BACKGROUND: Poly-l-lactic acid (PLLA) is an effective treatment for patients
      seeking to correct volume loss due to aging. Although the Food and Drug
      Administration has approved PLLA for use in people with the human
      immunodeficiency virus (HIV), it is well-suited for patients seeking cosmetic
      treatment. OBJECTIVE: To evaluate the efficacy and incidence of adverse events of
      HIV-negative patients treated with PLLA for volume restoration. MATERIALS AND
      METHODS: This is a retrospective, single-center study of 130 HIV-negative
      patients treated with PLLA from 2003 to 2008. Patient satisfaction and incidence
      of adverse reactions were evaluated. RESULTS: The most common reaction to PLLA
      treatment was the formation of nodules (8.5%). Almost all of the nodules were
      palpable; only one was visible. Treatment areas with the highest incidence of
      post-treatment nodules were the hands (12.5%) and cheeks (7.2%). Overall,
      patients were satisfied, with 55% having good to excellent correction; 75% of
      patients with five or more treatments rated their correction as good to
      excellent. Sixty-eight percent of all patients would repeat the procedure again.
      CONCLUSION: PLLA is a safe, biodegradable volumizer used to reverse the signs of
      aging by gradually correcting volume loss. Patients should be aware of possible
      adverse reactions during the course of treatment. Nodule formation is low, with
      most patients having good to excellent correction.

PMID- 20039920
TI  - Where is it? The utility of biopsy-site photography.
AB  - BACKGROUND: With wrong-site surgery being one of the major causes of medical
      lawsuits in the United States, tools to confirm location are essential. A
      previous survey of 300 Mohs surgeons revealed that 14% of malpractice cases were
      due to wrong-site surgery. In dermatologic surgery, photography is helpful in
      precisely locating biopsy sites. OBJECTIVES: We present a case series of 34
      biopsy-proven cutaneous head and neck malignancies performed in our university
      based dermatology clinic, comparing the reliability of patient and blinded
      dermatologist identification with that of biopsy-site photography. RESULTS: Of 34
      biopsy sites, the patient and the blinded dermatologist incorrectly identified
      four (12%). The patient alone incorrectly identified an additional six biopsy
      sites, resulting in a total of 10 (29%) cases incorrectly identified by the
      patient. There were no instances in which the patient correctly identified the
      biopsy site and the blinded dermatologist incorrectly identified it. CONCLUSION:
      In our current medical environment, in which more than 90% of health care is
      delivered in a clinic setting, wrong-site surgery is certainly underreported. In
      adopting a zero-tolerance policy for wrong-site surgeries, biopsy-site
      photography saves time, money, and potential frustration, hopefully eliminating
      the number of excisions performed on the wrong site.

PMID- 20039922
TI  - Simplified cellular grafting for treatment of vitiligo and piebaldism: the "6
      well plate" technique.
AB  - BACKGROUND: Vitiligo is a disfiguring depigmenting dermatosis that affects
      approximately 0.5% to 1% of the general population regardless of race and sex. In
      patients with stable vitiligo who fail conventional therapies, surgical
      transplant offers a viable alternative. Noncultured cellular grafting offers the
      advantage of repigmenting vitiligo 5 to 10 times the size of the donor skin and
      can be completed on the same day on an outpatient basis. In recent years, ways to
      simplify this procedure have been explored, including the use of commercially
      available kits. OBJECTIVES: To simplify the extraction of epidermal cells from
      donor skin using a 6-well plate and to evaluate the clinical efficacy of this
      simplified technique in repigmenting stable vitiligo and piebaldism. METHODS:
      Four patients with focal or segmental vitiligo and one with piebaldism were
      treated using the simplified noncultured cellular grafting protocol. Percentage
      of repigmentation 6 months after grafting was objectively measured using digital
      contour mapping. RESULTS: Patients with stable segmental or focal vitiligo
      achieved 65% to 92% repigmentation 6 months after grafting; the treated sites
      involved face or limbs. The patient with piebaldism achieved 86% repigmentation.
      One year after grafting, the extent of repigmentation remained for all patients.
      CONCLUSION: This set-up is simple and inexpensive; it reduces cell preparation
      time, amount of reagents used, and costs, and obviates the need of a laboratory
      for extraction of epidermal cells.

PMID- 20039925
TI  - Chicken embryonic stem cells as a non-mammalian embryonic stem cell model.
AB  - Embryonic stem cells (ESCs) were isolated in the early 1980s from mouse and in
      the late 1990s from primate and human. These cells present the unique property of
      self-renewal and the ability to generate differentiated progeny in all embryonic
      lineages both in vitro and in vivo. The mESCs (mouse embryonic stem cells) can
      contribute to both somatic and germinal lineages once re-injected into a
      recipient embryo at the blastocyst stage. In avian species, chicken embryonic
      stem cells (cESCs) have been isolated from the in vitro culture of early chicken
      blastodermal cells (cBCs) taken from stage X embryo (EG&K) These cESCs can be
      maintained under specific culture conditions and have been characterized on the
      basis of their morphology, biochemical features, in vitro differentiation
      potentialities and in vivo morphogenetic properties. The relationship between
      these cESCs and some of the chicken germ cells identified and grown under
      specific culture conditions are still under debate, in particular with the
      identification of the Cvh gene as a key factor for germ cell determination.
      Moreover, by cloning the avian homologue of the Oct4 mammalian gene, we have
      demonstrated that this gene, as well as the chicken Nanog gene, was involved in
      the characterization and maintenance of the chicken pluripotency. These first
      steps toward the understanding of pluripotency control in a non-mammalian species
      opens the way for the development and characterization of putative new cell types
      such as chicken EpiSC and raises the question of the existence of reprogramming
      in avian species. These different points are discussed.

PMID- 20039923
TI  - Squamous cell carcinoma of the scalp in organ transplant recipients: exploring
      mechanisms for recurrence and treatment guidelines.
AB  - BACKGROUND: The scalp is a target for squamous cell carcinoma (SCC) in male organ
      transplant recipients (OTRs) with alopecia. These tumors can behave aggressively
      and are associated with high recurrence, morbidity, and mortality. Treatment
      guidelines are needed for SCC in the scalp of OTRs. OBJECTIVE: To explore the
      clinical and histologic features associated with SCC recurrence and
      aggressiveness in the scalp of OTRs. We review the mechanisms involved as they
      relate to a case. An algorithm for evaluation and treatment is introduced.
      METHODS: An OTR presented with poorly differentiated SCC of the scalp that
      recurred on three occasions after Mohs micrographic surgery (MMS). The final
      recurrence invaded the bone and cranial cavity. We discuss the difficulties
      encountered in evaluating and treating these patients. RESULTS: This patient had
      multiple factors associated with high tumor recurrence and aggressiveness. These
      were explored, and an algorithm was created. CONCLUSION: SCC in the scalp of OTRs
      presents challenges for evaluation and management. We must be vigilant to monitor
      for recurrence, perineural invasion, bone invasion, multiple-field tumors, and
      metastasis. An understanding of the mechanisms of tumor recurrence will assist us
      in preventing morbidity and mortality in this subset of patients.

PMID- 20039927
TI  - Spatially and temporally regulated expression of specific heparan sulfate
      epitopes in the developing mouse olfactory system.
AB  - Heparan sulfate (HS) comprises a structurally diverse group of glycosaminoglycans
      present ubiquitously on cell surfaces and in the extracellular matrix. The
      spatially and temporally regulated expression of specific HS structures is
      essential for various developmental processes in the nervous system but their
      distributions in the mouse olfactory system have not been explored. Here, we
      examined the spatiotemporal distribution of particular HS species in the
      developing mouse olfactory system using three structure-specific monoclonal
      antibodies (HepSS-1, JM403 and NAH46). The major findings were as follows. (i)
      During olfactory bulb morphogenesis, the HepSS-1 epitope was strongly expressed
      in anterior telencephalic cells and coexpressed with fibroblast growth factor
      receptor 1. (ii) In early postnatal glomeruli, the JM403 epitope was expressed at
      different levels among individual glomeruli. The expression pattern and levels of
      the JM403 epitope were both associated with those of ephrin-A3. (iii) In the
      vomeronasal system, the JM403 epitope was expressed in all vomeronasal axons but
      became increasingly restricted to vomeronasal axons terminating in the anterior
      region of the accessory olfactory bulb by 3 weeks of age. Our results demonstrate
      that each HS epitope exhibits a unique expression pattern during the development
      of the mouse olfactory system. Thus, each HS epitope is closely associated with
      particular developmental processes of the olfactory system and might have a
      particular role in developmental events.

PMID- 20039926
TI  - Functional analysis of chick heparan sulfate 6-O-sulfotransferases in limb bud
      development.
AB  - Heparan sulfate (HS) interacts with numerous growth factors, morphogens,
      receptors, and extracellular matrix proteins. Disruption of HS synthetic enzymes
      causes perturbation of growth factor signaling and malformation in vertebrate and
      invertebrate development. Our previous studies show that the O-sulfation patterns
      of HS are essential for the specific binding of growth factors to HS chains, and
      that depletion of O-sulfotransferases results in remarkable developmental defects
      in Drosophila, zebrafish, chick, and mouse. Here, we show that inhibition of
      chick HS-6-O-sulfotransferases (HS6ST-1 and HS6ST-2) in the prospective limb
      region by RNA interference (RNAi) resulted in the truncation of limb buds and
      reduced Fgf-8 and Fgf-10 expressions in the apical ectodermal ridge and in the
      underlying mesenchyme, respectively. HS6ST-2 RNAi resulted in a higher frequency
      of limb truncation and a more marked change in both Fgf-8 and Fgf-10 expressions
      than that achieved with HS6ST-1 RNAi. HS6ST-1 RNAi and HS6ST-2 RNAi caused a
      significant but distinct reduction in the levels of different 6-O-sulfation in
      HS, possibly as a result of their different substrate specificities. Our data
      support a model where proper levels and patterns of 6-O-sulfation of HS play
      essential roles in chick limb bud development.

PMID- 20039928
TI  - Stem cell system in asexual and sexual reproduction of Enchytraeus japonensis
      (Oligochaeta, Annelida).
AB  - Enchytraeus japonensis is a small oligochaete species that proliferates asexually
      via fragmentation and regeneration. As sexual reproduction can also be induced,
      it is a good model system for the study of both regenerative and germline stem
      cells. It has been shown by histological study that putative mesodermal stem
      cells called neoblasts, and dedifferentiated epidermal and endodermal cells are
      involved in blastema formation. Recently, we isolated three region-specific
      marker genes expressed in the digestive tract and showed by in situ hybridization
      that morphallactic as well as epimorphic regulation of the body patterning occurs
      during regeneration. We also cloned two vasa-related genes and analyzed their
      expression during development and in mature worms that undergo sexual
      reproduction. The results arising form these studies suggest that the origin and
      development of germline stem cells and neoblasts may be independent. Furthermore,
      we carried out functional analysis using RNA interference (RNAi) and showed that
      a novel gene termed grimp is required for mesodermal cell proliferation at the
      initial stages of regeneration. These findings indicate that the stem cell system
      in E. japonensis is regulated by both internal and external environmental
      factors.

PMID- 20039929
TI  - Reduced cannabinoid receptor 1 protein in subcutaneous adipose tissue of obese.
AB  - BACKGROUND: Cannabinoid 1 receptors are identified in various tissues involved in
      the internal metabolism including adipose tissue and the endocannabinoid system
      is claimed to be overactive in the obese state. To study the potential
      involvement of cannabinoid receptor 1 in the endocannabinoid system over-activity
      in adipose tissue in the obese state, we investigated the cannabinoid receptor 1
      levels in adipose tissue from different fat depots in lean and obese humans.
      MATERIALS AND METHODS: The adipose tissue samples were analysed by Western blot
      and by RT-PCR. RESULTS: Both the gene expression and the protein of cannabinoid
      receptor 1 were lower in subcutaneous abdominal adipose tissue from obese
      subjects as compared with lean subjects (P < 0.01 and P = 0.058). Moreover, in
      lean subjects, the level of cannabinoid receptor 1 was significantly higher in
      subcutaneous adipose tissue compared with visceral adipose tissue (P < 0.05) for
      both gene expression and protein. The level of cannabinoid receptor 1 was similar
      between the two depots in obese subjects. The expression of cannabinoid receptor
      1 was higher in subcutaneous gluteal adipose tissue as compared with subcutaneous
      abdominal adipose tissue (P < 0.05). CONCLUSION: We found in lean subjects, a
      robust lower level of cannabinoid receptor 1 in visceral adipose tissue compared
      with subcutaneous adipose tissue (both RNA and protein levels), but similar
      levels of cannabinoid receptor 1 between the two depots in obese subjects. Our
      present findings do not indicate that cannabinoid receptor 1 is directly involved
      in the endocannabinoid system over-activity in adipose tissue in obesity.

PMID- 20039933
TI  - The silent gap between epilepsy surgery evaluations and clinical practice
      guidelines.

PMID- 20039936
TI  - Quality of sleep in primary focal dystonia: a case-control study.
AB  - BACKGROUND: Sleep disturbances are common in patients with movement disorders.
      Evaluating quality of sleep is of primary importance because of the effect that
      nocturnal and daytime sleep abnormalities exert on general health status.
      However, quality of sleep has never been addressed in detail in patients with
      dystonia. The aim of this case-control study was to analyse quality of sleep in
      patients with the two most common forms of primary focal dystonia, blepharospasm
      (BSP) and cervical dystonia (CD). METHODS: We evaluated quality of sleep
      (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth
      Sleepiness Scale, ESS) in 98 patients with focal adult-onset dystonia (52 with
      BSP; 46 with CD) and in a group of 56 age-and gender-matched healthy subjects.
      The Beck Depression Inventory (BDI) was used for the evaluation of depressive
      symptomatology. RESULTS: Quality of sleep was impaired (significantly higher PSQI
      scores) in both groups of patients. However, differences in PSQI scores between
      patients with CD and control subjects were partly confounded by BDI scores,
      whereas differences in PSQI scores between patients with BSP and control subjects
      were not influenced by BDI. Excessive daytime sleepiness was not significantly
      more frequent than in control subjects in either patients with BSP or patients
      with CD. CONCLUSIONS: This study suggests that the assessment and treatment of
      insomnia-related complaints should be considered in global management plans of
      patients with focal dystonia, particularly in those affected by BSP.

PMID- 20039934
TI  - Empirical evidence of underutilization of referrals for epilepsy surgery
      evaluation.
AB  - BACKGROUND: Epilepsy surgery is a treatment that can cure patients with
      intractable epilepsy. This study investigates whether referrals for epilepsy
      surgery evaluation are underutilized. METHODS: Patients with epilepsy aged 18-60
      years were identified in a computerized registry held by public health care
      providers in a Swedish county using ICD codes. Clinical data and data on referral
      status for epilepsy surgery were obtained from the patients' medical records.
      Potential candidates for epilepsy surgery evaluation were identified using pre
      specified criteria. Obstacles for referral were analysed by comparing clinical
      data in patients who were considered for referral and those who were not.
      Appropriateness of non-referral was evaluated against recommendations from the
      Swedish Council on Technology in Health Care (SBU). RESULTS: Of 378 patients with
      epilepsy in the registry, 251 agreed to participate. Of 251, 40 were already
      referred patients and 48 patients were identified as potential candidates for
      epilepsy surgery evaluation by study criteria. Referral had been considered but
      not performed in 15 of the potential candidates. Potential candidates not
      considered for referral were less likely to have seen a neurologist, to have had
      an EEG, CT and MRI, and more likely to have cognitive disturbances. Following the
      recommendations by the SBU, 28 of 48 potential candidates were identified as
      inappropriately not referred patients. CONCLUSION: The number of missed referrals
      for epilepsy surgery evaluation was estimated to be 60 per 100,000 inhabitants.
      Several important obstacles were found for not referring patients for epilepsy
      surgery evaluation.

PMID- 20039931
TI  - High-dose tirofiban with enoxaparin and inflammatory markers in high-risk
      percutaneous intervention.
AB  - AIM: The study assessed the benefit of high bolus dose tirofiban (HD-tirofiban)
      with enoxaparin compared with HD-tirofiban with unfractionated heparin (UFH). The
      study examined markers of platelet activation, thrombin generation and
      inflammation. MATERIALS AND METHODS: The study is a prospective single centre
      open-label trial of patients with high-risk acute coronary syndrome treated with
      percutaneous intervention (PCI) who were randomized to anticoagulation with UFH
      or enoxaparin with HD-tirofiban (25 microg kg(-1) bolus). This study measured a
      panel of platelet activation markers, inflammatory biomarkers and thrombus
      generation between the two groups. RESULT: Sixty patients undergoing high-risk
      PCI were enroled in the study. Platelet inhibition as assessed by whole blood
      aggregometry following HD-tirofiban infusion was similar in both the UFH and
      enoxaparin groups. CD40 ligand expression on platelets was significantly reduced
      following PCI with HD-tirofiban and either UFH or enoxaparin. Following PCI,
      there were significant reductions measured in other markers of platelet
      activation including PAC-1, P selectin, factor V/Va, platelet-monocyte aggregates
      and monocyte expression of Mac-1 as determined by analysis of venous blood
      samples using flow cytometry. Prothrombin fragment 1+2, D-dimer, von Willebrand
      factor and high sensitive C-reactive protein levels were significantly less post
      PCI in the enoxaparin group compared with those patients receiving UFH.
      CONCLUSION: The combination of HD tirofiban with enoxaparin resulted in an
      attenuated inflammatory response when compared with that of the combination of HD
      tirofiban with UFH.

PMID- 20039930
TI  - Suppressive effect of COX2 inhibitor on the progression of adipose inflammation
      in high-fat-induced obese rats.
AB  - BACKGROUND: The aim was to examine whether the inhibition of selective
      cyclooxygenase (COX) 2 activation could suppress the development of inflammatory
      reaction in visceral and subcutaneous abdominal fats of high-fat-induced obese
      rats. MATERIALS AND METHODS: The rats were fed separately regular diet (CONT),
      high-fat diet ad libitum or energy-restrictedly (HFr) for 12 weeks. Rats fed high
      fat diet ad libitum were further divided into those co-treated with vehicle
      (HFa), a selective COX2 inhibitor-celecoxib (HFa-Cel) or nimesulide (HFa-Nim).
      Oral glucose tolerance test (OGTT) was performed at the end of weeks 4, 8, 12.
      Another set of rats with similar grouping was divided into those with a 4-, 8- or
      12-week intervention for tissue sampling. RESULTS: Body and epididymal fat
      weights were increased similarly in HFa, HFa-Cel and HFa-Nim. Time-dependent
      increases in plasma insulin, triglyceride, impaired OGTT shown in HFa were
      significantly reversed in HFa-Cel and HFa-Nim. The obese-linked increases in gene
      expressions of COX-2, monocyte chemoattractant protein-1 (MCP-1) and tumour
      necrosis factor-alpha (TNF-alpha) in epididymal and subcutaneous fats (especially
      in the former) were significantly suppressed in HFa-Cel and HFa-Nim. The protein
      contents of MCP-1 and TNF-alpha in epididymal fats were changed consistently with
      their gene expressions. Plasma MCP-1 was increased time-dependently in HFa and
      suppressed in HFa-Cel and HFa-Nim. The increased CD68 positive cells showed in
      both epididymal and subcutaneous fats of HFa were significantly attenuated in HFa
      Cel and HFa-Nim. CONCLUSIONS: Our findings suggest that COX2 activation is
      crucially involved in the development of inflammatory response in adipose tissues
      of high-fat-induced obese rats.

PMID- 20039935
TI  - Cerebrospinal fluid biomarkers and white matter lesions: can we know more?

PMID- 20039938
TI  - Temporal features of magnetic resonance imaging and spectroscopy in non-ketotic
      hyperglycemic chorea-ballism patients.
AB  - BACKGROUND: Non-ketotic hyperglycemic chorea-ballism (NKHCB) had special
      reversible hyperintense on T1-weighted imaging (T1WI) lesion in comparsion to
      gray matter. However, the mechanism accounts for these lesions is still unclear.
      METHODS: Patients diagnosed with NKHCB were recruited from 2002 to 2004. The
      demographic, clinical, magnetic resonance imaging (MRI), and spectroscopy (MRS)
      features were recorded at acute and remission phase. RESULTS: In 18 patients with
      NKHCB, the blood sugar level at onset was significantly higher than that after
      being free from chorea-ballism (419.50 +/- 257.33 vs. 198.22 +/- 53.97 mg/dl, P =
      0.001). The serum osmolality dropped from 318.33 +/- 15.21 mOsm/kg at onset to
      292.50 +/- 7.85 mOsm/kg after recovery (P < 0.001). All patients displayed T1
      hyperintense lesions at contralateral basal ganglia at acute phase. Eight
      patients receiving follow-up MRI at remission phase, all T1 hyperintense lesions
      at the basal ganglia regressed. The ratios between choline-containing compounds
      and creatine at acute and remission phases were significant higher in lesion than
      in normal side, respectively (acute phase: 1.12 +/- 0.23 vs. 0.72 +/- 0.28, P =
      0.038; remission phase: 1.23 +/- 0.47 vs. 0.68 +/- 0.15, P = 0.013). The lactate
      peaks present at 1.3 ppm on the lesion side either in acute or in remission phase
      of most case. CONCLUSIONS: The clinical, MRI, and MRS findings suggest that the
      mechanisms responsible for NKHCB may be a reversible ischaemia insult potentiated
      by hyperglycemia.

PMID- 20039939
TI  - Large differences in levodopa dose requirement in Parkinson's disease: men use
      higher doses than women.
AB  - BACKGROUND AND PURPOSE: The characteristics of levodopa dosing are not well
      described in the literature. The aims were to investigate the use of levodopa in
      a nationwide Swedish survey and to study the characteristics of low-dose and high
      dose patients with Parkinson's disease (PD) in a university hospital. METHODS:
      Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected
      from the prescribed drug register. Daily levodopa doses were estimated. Records
      of 504 patients with PD who visited the neurology clinic at Uppsala University
      Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg
      levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with
      at least 5 years of PD duration. RESULTS: In total, 33 534 levodopa users with >
      or = 1 levodopa purchase were found. Daily levodopa dose range was large; median
      daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half
      (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were
      treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P <
      0.0001). Patients with high dose at 5 years PD duration continuously increased
      their dosage the following years, whereas low-dose patients did not. The
      occurrence of dyskinesias was about the same in both groups despite the large
      difference in levodopa dose. CONCLUSIONS: We conclude that the levodopa
      requirement in PD ranges considerably, and that men use higher levodopa dose than
      women. Levodopa requirement is constant during the progression of the disease in
      low-dose patients but increases in high-dose patients.

PMID- 20039942
TI  - Different responses to interferon beta-1b treatment in patients with
      neuromyelitis optica and multiple sclerosis.
AB  - BACKGROUND: Although the benefit of treatment for relapsing-remitting multiple
      sclerosis (MS) is firmly established, whether interferon beta-1b (IFNB-1b)
      therapy is efficacious for neuromyelitis optica (NMO) has been debated. METHODS:
      We reviewed the responses to IFNB-1b treatment in 18 patients with relapsing NMO
      and compared the results with those from 38 patients with relapsing-remitting MS.
      We compared clinical characteristics, the annualized relapse rate (ARR) and the
      probability of being relapse free before and after IFNB-1b treatment in patients
      with NMO and MS. RESULTS: The proportion of patients with more than 50% increase
      in the ARR after IFNB-1b treatment was much higher in NMO than in MS (P = 0.046).
      ARR was significantly lower in patients with MS after IFNB-1b administration than
      before (P = 0.015), but not in NMO. Kaplan-Meier and log-rank statistical
      analyses revealed that relapse-free rates were lower in NMO than MS after IFNB-1b
      treatment (P = 0.032). The analyses also showed lower relapse-free rates during
      the pre-IFNB-1b treatment period than the post-IFNB-1b treatment period in MS (P
      < 0.001), but not in NMO. CONCLUSION: IFNB-1b treatment does not appear to be
      effective for preventing relapse in NMO likely because of differences between the
      immune-pathogenesis of NMO and MS.

PMID- 20039940
TI  - Synergistic effect of two oxidative stress-related genes (heme oxygenase-1 and
      GSK3beta) on the risk of Parkinson's disease.
AB  - BACKGROUND: Oxidative stress is a central factor in the pathogenesis of
      Parkinson's disease (PD). Heme oxygenase-1 (HO-1) is an antioxidant protein
      expressed in response to oxidative challenge, and its expression levels are
      inversely correlated with glycogen synthase kinase-3beta (GSK3beta) activity.
      Underexpression of HO-1 in concert with an upregulation of GSK3beta would result
      in a less effective antioxidant response and might increase the risk of PD.
      METHODS: We examined two functional polymorphism in the promoter regions of HO-1
      (-413, rs2071746) and GSK3beta (-157, rs6438552) in a group of 251 Spanish
      patients with PD and 234 controls. RESULTS: Subjects carrying both the HO-1 (
      413, rs2071746) TT genotype and the GSK3beta (-157, rs6438552) TT genotype had a
      four times higher risk of developing PD than subjects without these genotypes
      (adjusted by age and sex OR = 4.12; 95% CI = 1.45-11.71; Bonferroni corrected P =
      0.024). CONCLUSIONS: Considering synergistic effects between polymorphisms in
      oxidative stress-related genes may help in determining the risk profile for PD.

PMID- 20039932
TI  - Pim-3 protects against hepatic failure in D-galactosamine (D-GalN)-sensitized
      rats.
AB  - BACKGROUND: Fulminant hepatic failure (FHF) has a high mortality resulted from
      massive hepatic apoptosis and haemorrhage necrosis; it is required to develop a
      valid therapy directed towards hepatocyte protection and regeneration. Pim-3, a
      hepatic growth stimulator, belongs to the serine/threonine kinase Pim-family that
      has been implicated in gp130-mediated induction of cell proliferation, protection
      from apoptosis downstream of Signal transducer and activator of transcription 3
      (STAT3) and vascular endothelial growth factor-A-dependent vasculogenesis and
      angiogenesis, thus is suggested to possibly play a role in the tissue repair of
      FHF. MATERIALS AND METHODS: Male Wistar rats received simultaneous
      intraperitoneal injections of lipopolysaccharide (LPS) (100 microg kg(-1)) and D
      galactosamine (D-GalN) (600 mg kg(-1)). One day prior to LPS/D-GalN
      administration, naked plasmid or Ringer's solution was injected via tail vein by
      hydrodynamics-based procedure. RESULTS: Exogenous Pim-3 gene protected against
      LPS/D-GalN-induced lethality with survival rate of more than 80% and improved the
      hepatic pathomorphism. The fractions of hepatic apoptotic-positive cells and the
      levels of caspase-3 activity were markedly lower in Pim-3-pretreated rats.
      Furthermore, exogenous Pim-3 significantly inhibited expression of tumour
      necrosis factor-alpha and interleukin-1beta in the liver, declined p53 and
      inducible nitric oxide synthase mRNAs levels, but elevated levels of Bcl-2
      protein, an anti-apoptosis member of Bcl-2 family, in the liver. Exogenous Pim-3,
      however, showed little effect on expression of Bax, a pro-apoptosis member of Bcl
      2 family. CONCLUSIONS: Pim-3 gene could protect rats from FHF by inhibiting liver
      apoptosis and improving inflammatory response of liver tissues, which could be
      associated with inhibiting expression of inflammatory mediators and promoting
      expression of anti-apoptosis protein Bcl-2.

PMID- 20039946
TI  - NMDA receptors-dependent plasticity in the phototaxis preference behavior induced
      by visual deprivation in young and adult flies.
AB  - Adult mammals have experience-dependent plasticity in visual system, but it is
      unclear whether adult insects also have this plasticity after the critical period
      of visual development. Here, we have established a modified Y-maze apparatus for
      investigating experience-dependent plasticity in Drosophila. Using this setup we
      demonstrate that flies after the critical period have bidirectional modifications
      of the phototaxis preference behavior (PPB) induced by visual deprivation and
      experience: Visual deprivation decreases the preference of flies for visible
      light, while visual experience exerts the opposite effect. We also found an age
      dependent PPB plasticity induced by visual deprivation. Molecular and cellular
      studies suggest that the N-methyl- d-aspartate receptors (NMDARs) mediate ocular
      dominance plasticity in visual cortex in mammals, but direct behavioral evidence
      is lacking. Here, we used the genetic approaches to demonstrate that NMDAR1,
      which is NMDARs subunit in Drosophila, can mediate PPB plasticity in young and
      adult flies. These findings provide direct behavioral evidence that NMDAR1
      mediates PPB plasticity in Drosophila. Our results suggest that mammals and
      insects have analogous mechanisms for experience-dependent plasticity and its
      regulation by NMDAR signaling.

PMID- 20039947
TI  - Does genetic background moderate the association between parental education and
      school achievement?
AB  - This study was conducted with a purpose to examine whether the T102C polymorphism
      of the serotonin receptor 2A (HTR2A) gene moderates the association between
      parental education and children's school achievement across nine compulsory
      school years. The study was carried out in a population-based sample of Finnish
      students (aged 9, 12 and 15 years, n = 982). It was found that the HTR2A gene was
      not related to the school achievement at any school level, but moderated the
      association between maternal education and the children's grade point averages.
      The T/T genotype carriers benefited most from high-maternal education, and
      suffered from a low one more than the carriers of the other variants of the HTR2A
      gene. The present finding may at least partly answer the important question why
      academic outcomes of environmental interventions vary even at the same
      intelligence levels of the students.

PMID- 20039944
TI  - A genome-wide association study identifies multiple loci associated with
      mathematics ability and disability.
AB  - Numeracy is as important as literacy and exhibits a similar frequency of
      disability. Although its etiology is relatively poorly understood, quantitative
      genetic research has demonstrated mathematical ability to be moderately
      heritable. In this first genome-wide association study (GWAS) of mathematical
      ability and disability, 10 out of 43 single nucleotide polymorphism (SNP)
      associations nominated from two high- vs. low-ability (n = 600 10-year-olds each)
      scans of pooled DNA were validated (P < 0.05) in an individually genotyped sample
      of (*)2356 individuals spanning the entire distribution of mathematical ability,
      as assessed by teacher reports and online tests. Although the effects are of the
      modest sizes now expected for complex traits and require further replication,
      interesting candidate genes are implicated such as NRCAM which encodes a neuronal
      cell adhesion molecule. When combined into a set, the 10 SNPs account for 2.9% (F
      = 56.85; df = 1 and 1881; P = 7.277e-14) of the phenotypic variance. The
      association is linear across the distribution consistent with a quantitative
      trait locus (QTL) hypothesis; the third of children in our sample who harbour 10
      or more of the 20 risk alleles identified are nearly twice as likely (OR = 1.96;
      df = 1; P = 3.696e-07) to be in the lowest performing 15% of the distribution.
      Our results correspond with those of quantitative genetic research in indicating
      that mathematical ability and disability are influenced by many genes generating
      small effects across the entire spectrum of ability, implying that more highly
      powered studies will be needed to detect and replicate these QTL associations.

PMID- 20039949
TI  - DJ-1-deficient mice show less TH-positive neurons in the ventral tegmental area
      and exhibit non-motoric behavioural impairments.
AB  - Loss of function of DJ-1 (PARK7) is associated with autosomal recessive early
      onset Parkinson's disease (PD), one of the major age-related neurological
      diseases. In this study, we extended former studies on DJ-1 knockout mice by
      identifying subtle morphological and behavioural phenotypes. The DJ-1 gene trap
      induced null mutants exhibit less dopamine-producing neurons in the ventral
      tegmental area (VTA). They also exhibit slight changes in behaviour, i.e.
      diminished rearing behaviour and impairments in object recognition. Furthermore,
      we detected subtle phenotypes, which suggest that these animals compensate for
      the loss of DJ-1. First, we found a significant upregulation of mitochondrial
      respiratory enzyme activities, a mechanism known to protect against oxidative
      stress. Second, a close to significant increase in c-Jun N-terminal kinase 1
      phosphorylation in old DJ-1-deficient mice hints at a differential activation of
      neuronal cell survival pathways. Third, as no change in the density of tyrosine
      hydroxylase (TH)-positive terminals in the striatum was observed, the remaining
      dopamine-producing neurons likely compensate by increasing axonal sprouting. In
      summary, the present data suggest that DJ-1 is implicated in major non-motor
      symptoms of PD appearing in the early phases of the disease-such as subtle
      impairments in motivated behaviour and cognition-and that under basal conditions
      the loss of DJ-1 is compensated.

PMID- 20039948
TI  - A genetic study of ADHD and activity level in infancy.
AB  - It is well known that there are strong genetic influences on attention-deficit
      hyperactivity disorder (ADHD), with genetic association studies providing good
      evidence for the involvement of the dopamine neurotransmitter system in its
      aetiology. Developmental origins of ADHD represent an interesting area of
      research to understand the genetics that underlie early appearing individual
      differences. However, understanding the molecular basis of ADHD requires
      accurate, unbiased, heritable measures that can be used for molecular genetic
      association analyses. We take two approaches to examine the genetics of ADHD
      behaviours in infancy. Using quantitative genetic techniques, we explore the
      relationship between objective measures of activity level (AL) in both home and
      laboratory environments as well as with parent ratings of ADHD symptoms in a
      population sample of 2-year-old twins. Molecular association analyses of these
      measures examine candidate genes previously associated with ADHD. We find that
      ADHD symptoms, AL in the home and AL in the lab represent heritable phenotypes in
      2-year-old infants. AL measured in the home has a strong genetic correlation with
      symptoms of ADHD, whereas AL in the lab correlates only modestly with the same
      ADHD measure. Genetic correlations suggest that AL in the home is more comparable
      than AL in the lab to ADHD behaviour and support the separation of all three for
      molecular analyses. There was modest evidence for association between DAT1, NET1
      and ADHD symptom scores, as well as between DAT1 and AL in the lab.

PMID- 20039952
TI  - Simulating seepage into mine shafts and tunnels with MODFLOW.
AB  - In cases when an equivalent porous medium assumption is suitable for simulating
      groundwater flow in bedrock aquifers, estimation of seepage into underground mine
      workings (UMWs) can be achieved by specifying MODFLOW drain nodes at the contact
      between water bearing rock and dewatered mine openings. However, this approach
      results in significant numerical problems when applied to simulate seepage into
      an extensive network of UMWs, which often exist at the mine sites. Numerical
      simulations conducted for individual UMWs, such as a vertical shaft or a
      horizontal drift, showed that accurate prediction of seepage rates can be
      achieved by either applying grid spacing that is much finer than the
      diameter/width of the simulated openings (explicit modeling) or using coarser
      grid with cell sizes exceeding the characteristic width of shafts or drifts by a
      factor of 3. Theoretical insight into this phenomenon is presented, based on the
      so-called well-index theory. It is demonstrated that applying this theory allows
      to minimize numerical errors associated with MODFLOW simulation of seepage into
      UMWs on a relatively coarse Cartesian grid. Presented examples include simulated
      steady-state groundwater flow from homogeneous, heterogeneous, and/or anisotropic
      rock into a vertical shaft, a horizontal drift/cross-cut, a ramp, two parallel
      drifts, and a combined system of a vertical shaft connected to a horizontal
      drift.

PMID- 20039951
TI  - Analytical solutions for flow fields near drain-and-gate reactive barriers.
AB  - Permeable reactive barriers (PRBs) are a popular technology for passive
      contaminant remediation in aquifers through installation of reactive materials in
      the pathway of a plume. Of fundamental importance are the degree of remediation
      inside the reactor (residence time) and the portion of groundwater intercepted by
      a PRB (capture width). Based on a two-dimensional conformal mapping approach
      (previously used in related work), the latter is studied in the present work for
      drain-and-gate (DG) PRBs, which may possess a collector and a distributor drain
      ("full" configuration) or a collector drain only ("simple" configuration).
      Inherent assumptions are a homogeneous unbounded aquifer with a uniform far
      field, in which highly permeable drains establish constant head boundaries.
      Solutions for aquifer flow fields in terms of the complex potential are derived,
      illustrated, and analyzed for doubly symmetric DG configurations and arbitrary
      reactor hydraulic resistance as well as ambient groundwater flow direction. A
      series of practitioner-friendly charts for capture width is given to assist in
      PRB design and optimization without requiring complex mathematics. DG PRBs are
      identified as more susceptible to flow divergence around the reactor than
      configurations using impermeable side structures (e.g., funnel-and-gate), and
      deployment of impermeable walls on drains is seen to mitigate this problem under
      certain circumstances.

PMID- 20039950
TI  - Morphology and ultrastructure of epilithic versus cryptic, microbial growth in
      lower Cambrian phosphorites from the Montagne Noire, France.
AB  - The lower Cambrian grainy phosphorites of the northern Montagne Noire occur
      interbedded with grey to black, laminated to massive shales and limestones
      deposited along the edge of a continental shelf, associated with slope-related
      facies and unstable substrates. The concentration of phosphate took place by
      repeated alternations of low sedimentation rates and condensation (hardgrounds),
      in situ early-diagenetic precipitation of fluorapatite, winnowing and polyphase
      reworking of previously phosphatized skeletons and hardground-derived clasts. The
      succession of repeated cycles of sedimentation, phosphate concentration, and
      reworking led to multi-event phosphate deposits rich in allochthonous particles.
      Phosphogenesis was primarily mediated by microbial activity, which is evidenced
      by the abundance of phosphatized putative microbial remains. These occur as
      smooth and segmented filaments, sheaths, and ovoid-shaped coccoids. These simple
      morphologies commonly form composite frameworks as a result of their aggregation
      and entanglement, leading to the record of biofilms, microbial mats, and complex
      networks. These infested the calcitic skeletonized microfossils that littered the
      substrate. Microbial activity evidences epilithic (anisotropic coatings on
      skeletons), euendolithic (perforating skeletal walls), and cryptoendolithic
      (lining inter- and intraparticulate pores) strategies, the latter dominated by
      bundles of filaments and globular clusters that grew along the cavities of
      helcionellids and hyoliths. According to their epilithic versus cryptic
      strategies, microbial populations that penetrated and dwelled inside hard
      skeletal substrates show different network and colonial morphologies. These early
      Cambrian shell concentrations were the loci of a stepwise colonization made by
      saprophytic to mutualistic, cyanobacterial-fungal consortia. Their euendolithic
      and cryptoendolithic ecological niches provided microbial refugia to manage the
      grazing impact mainly led by metazoans.

PMID- 20039954
TI  - Resolution of menstrually related migraine following aggressive treatment for
      breast cancer.
AB  - Hormonal influences associated with the female menstrual cycle play strong roles
      in both migraine and particular types of breast cancer, but there is limited
      literature on the effects of breast cancer treatment regimens in women with
      migraine. The present case describes resolution of menstrually related migraine
      following aggressive treatment for infiltrating ductal carcinoma (neoadjuvant
      chemotherapy, single radical mastectomy, and locoregional radiation therapy) that
      was maintained with supplemental treatment using tamoxifen, an anti-estrogenic
      agent. This novel case is presented to stimulate further research into the
      hormonal mechanisms underlying migraine.

PMID- 20039953
TI  - Triptan use as a function of cardiovascular risk. A population-based study.
AB  - AIM: To estimate the proportion of individuals with migraine using triptan
      therapy as a function of their cardiovascular (CV) profile and disease severity.
      METHODS: As a part of the American Migraine Prevalence and Prevention study, we
      identified migraineurs representative of the U.S. adult population. Triptan use
      was estimated as a function of presence of CV disease (CVD), of CV risk factors,
      and by level of migraine-related disability. RESULTS: Our sample consists of 6102
      individuals with migraine. Compared with migraineurs without risk factors for
      CVD, triptans were significantly less likely to be used in individuals with
      diabetes (11.5% vs 18.3%, OR = 0.6, 95% CI = 0.5-0.7), hypertension (14.8%, OR =
      0.8, 0.7-0.9) and by smokers (12.9%, OR = 0.7, 0.6-0.8). Similar findings were
      seen for individuals with established CVD. As contrasted to individuals without
      CVD, those with myocardial infarct (8.5% vs 18.5%, OR = 0.4, 0.3-0.7), stroke
      (7%, OR = 0.6, 0.3-0.9) and heart surgery (9.3%, OR = 0.5, 0.4-0.7) were less
      likely to use triptans. Use of triptan increased as a function of disability
      regardless of CVD status or presence of CV risk factors. CONCLUSION: Triptan use
      is lower in those with vs without CV risk, suggesting that doctors and/or
      patients fear using triptans in individuals at risk to CVD. Furthermore, triptan
      use in those with established CVD increases with headache-related disability,
      suggesting that patients and providers balance risks and benefits. Additional and
      analytical data are needed on the safety of triptans in the setting of CVD risk.
      This study has not assessed adequacy of care.

PMID- 20039956
TI  - Cytokines in idiopathic intracranial hypertension CSF.

PMID- 20039957
TI  - Involvement of pro-nociceptive 5-HT2A receptor in the pathogenesis of medication
      overuse headache.
AB  - OBJECTIVES: To determine the involvement of 5-HT(2A) (5-HT(2A)) receptor in the
      process of trigeminal plasticity induced by chronic analgesic exposure and in the
      process of inflammatory-induced thermal hyperalgesia. BACKGROUND: Derangement in
      5-HT(2A) serotonin receptor has been reported to implicate in pathogenesis of
      medication-overuse headache. No clear explanation concerning the precise roles of
      these receptors in the process. METHODS: Wistar rats were daily administered with
      paracetamol (200 mg/kg) for 30 days. On the next day, ketanserin, a 5-HT(2A)
      antagonist, or saline was given prior to cortical spreading depression (CSD)
      induction. Electrocorticogram, cortical blood flow, Fos and 5-HT(2A)
      immunoreactivity in cortex and trigeminal pathway were studied. In the other
      experiment, complete Freund's adjuvant was injected into the rat hind paw to
      induce tissue inflammation. Three days later, ketanserin was given and noxious
      heat was applied to both inflamed and noninflamed paws. The response between 2
      sides was compared by measuring paw withdrawal latency. RESULTS: Chronic
      paracetamol exposure led to an increase in CSD frequency and CSD-evoked Fos
      expression in cerebral cortex indicating the increase in neuronal excitability.
      Prolonged medication exposure also facilitated trigeminal nociception as evident
      by an increase in CSD-evoked Fos expression in trigeminal nucleus caudalis. The
      expression of 5-HT(2A) receptor in cerebral cortex and trigeminal ganglia was
      enhanced by chronic paracetamol administration. Pretreatment with ketanserin
      significantly attenuated these effects. The second experiment showed that
      ketanserin was able to lengthen the paw withdrawal latency in the inflamed side
      but did not alter nociceptive response in the noninflamed side. CONCLUSION: These
      findings suggest that up-regulation of pro-nociceptive 5-HT(2A) receptor is an
      important step in the process of cortical hyper-excitation and nociceptive
      facilitation induced by chronic analgesic exposure.

PMID- 20039958
TI  - A shortened version of the Headache-Specific Locus of Control Scale in Spanish
      population.
AB  - BACKGROUND AND OBJECTIVE: Further questions need to be addressed in the
      evaluation of locus of control (LOC) in headaches, such as reducing scale length
      and adapting them to diverse cultural environments, as in the case of Spain.
      METHODS: We perform a confirmatory factor analysis of the most outstanding items
      contained in the Headache-Specific Locus of Control Scale in the responses of 118
      patients suffering from headaches who received assistance at public health care
      centers in the province of Seville (Spain). RESULTS: The adjustment was positive,
      thus confirming the original structure of 3 factors: internal locus of control
      (LOC-I), health care professionals' LOC, and chance locus of control (LOC-C).
      Scale validation was performed by examining associations both with headache
      clinical parameters and psychological measures. The latter included self
      efficacy, internal language, coping strategies, and pain behaviors. LOC-C results
      deserve special mention, supporting the idea that it seems more important to
      avoid that patients develop LOC-C rather than boosting LOC-I and LOC-P
      expectations. CONCLUSIONS: The so-called Headache-Specific Locus of Control Scale
      Short Form 9 has turned out to be a parsimonious (9 items), valid, and reliable
      measure of headache LOC.

PMID- 20039959
TI  - Prophylactic etoricoxib is effective in preventing Yom Kippur headache: a placebo
      controlled double-blind and randomized trial of prophylaxis for ritual fasting
      headache.
AB  - BACKGROUND: Religious fasting is associated with headache. This has been
      documented as "Yom Kippur Headache" and "First-of-Ramadan Headache." Rofecoxib
      (Vioxx(r)), a cyclooxygenase-2 (Cox-2) inhibitor with a 17-hour half-life, has
      been shown to be effective in preventing fasting headache when taken just prior
      to the 25-hour Yom Kippur fast. Unfortunately for fasters rofecoxib is no longer
      available. We hypothesized that etoricoxib, another Cox-2 inhibitor with a longer
      half-life, would also be effective in preventing fasting headache. METHODS: We
      performed a double-blind randomized prospective trial of etoricoxib 120 mg vs
      placebo, taken just prior to the onset of fasting, Yom Kippur 2008. Healthy
      adults aged 18-65 years were enrolled from the community. Subjects completed a
      demographic data form and questions regarding headache history and a post-fast
      survey on headache during the fast. We compared incidence, time of onset and
      intensity of headache, general ease of fasting, and side effects in control and
      treatment groups. RESULTS: We enrolled 211 patients and 195 completed the post
      fast questionnaire (92%). Of those subjects receiving etoricoxib (n=99), 36 or
      36.4% vs 65 or 67.7% of the placebo group (n=96) developed any headache during
      the fast (P< .0001). Median severity of headache in the treatment group was
      significantly lower for the treatment group (3.0 vs 5.0 on a visual analog scale
      of 10; P= .024). Also, participants in the treatment group reported an easier
      fast than the placebo group, as compared with previous fasting experience (4.0 vs
      3.5 on a scale of 1-5; P< .0001). CONCLUSION: Etoricoxib 120 mg taken prior to a
      25-hour ritual fast decreases incidence of and attenuates fasting headache.

PMID- 20039960
TI  - Electronic momentary assessment of weather changes as a trigger of headaches in
      children.
AB  - BACKGROUND: Variables that are thought to precipitate migraine or tension-type
      headache episodes in children hitherto have only been studied using retrospective
      reports. As such, there is little empirical evidence to support the actual
      predictive association between presumed headache triggers and actual headache
      occurrence in children. OBJECTIVE: The present study sought to determine if
      fluctuations in weather, a commonly reported headache trigger in children,
      predict increased likelihood of headache occurrence when evaluated using rigorous
      prospective methodology ("electronic momentary assessment"). METHODS: Twenty-five
      children (21 girls, 4 boys) between the ages of 8-17 years attending a new
      patient neurology clinic appointment and having a diagnosis of chronic migraine,
      chronic tension-type, or episodic migraine headache (with or without aura)
      participated in the study. Children completed baseline measures on headache
      characteristics, presumed headache triggers, and mood and subsequently were
      trained in the use of electronic diaries to record information on headaches.
      Children then completed thrice daily diaries on handheld computers for a 2-week
      time period (42 assessments per child) while data on weather variables
      (temperature, dew point temperature, barometric pressure, humidity,
      precipitation, and sunlight) in the child's geographic location were recorded
      each time a diary was completed. Data were analyzed using multilevel models.
      RESULTS: Of the weather variables, relative humidity and presence of
      precipitation were significantly predictive of new headache onset, with nearly a
      3-fold increase in probability of headache occurrence during times of
      precipitation or elevated humidity in the child's area, b = 0.38, t(821) = 2.10,
      P = .04, and b = 0.02, t(821) = 2.81, P = .01, respectively. These associations
      remained after accounting for fluctuations in mood, and associations were not
      significantly stronger in children who at baseline thought that weather was a
      headache trigger for them. Changes in temperature, dew point temperature,
      barometric pressure, and sunlight were not significantly predictive of new
      headache episode occurrence in this sample. CONCLUSIONS: Results of the present
      study lend some support to the belief commonly held by children with recurrent
      headaches that weather changes may contribute to headache onset. Although
      electronic momentary assessment methodology was found to be feasible in this
      population and to have the potential to identify specific headache triggers for
      children, it remains to be determined how best (or even whether) to incorporate
      this information into treatment recommendations.

PMID- 20039943
TI  - The hypocretin-orexin system regulates cocaine self-administration via actions on
      the mesolimbic dopamine system.
AB  - Recent evidence suggests that the hypocretin-orexin system participates in the
      regulation of reinforcement processes. The current studies examined the extent to
      which hypocretin neurotransmission regulates behavioral and neurochemical
      responses to cocaine, and behavioral responses to food reinforcement. These
      studies used a combination of fixed ratio, discrete trials, progressive ratio and
      threshold self-administration procedures to assess whether the hypocretin 1
      receptor antagonist, SB-334867, reduces cocaine self-administration in rats.
      Progressive ratio sucrose self-administration procedures were also used to assess
      the extent to which SB-334867 reduces responding to a natural reinforcer in food
      restricted and food-sated rats. Additionally, these studies used microdialysis
      and in vivo voltammetry in rats to examine whether SB-334867 attenuates the
      effects of cocaine on dopamine signaling within the nucleus accumbens core.
      Furthermore, in vitro voltammetry was used to examine whether hypocretin knockout
      mice display attenuated dopamine responses to cocaine. Results indicate that when
      SB-334867 was administered peripherally or within the ventral tegmental area, it
      reduced the motivation to self-administer cocaine and attenuated cocaine-induced
      enhancement of dopamine signaling. SB-334867 also reduced the motivation to self
      administer sucrose in food-sated but not food-restricted rats. Finally,
      hypocretin knockout mice displayed altered baseline dopamine signaling and
      reduced dopamine responses to cocaine. Combined, these studies suggest that
      hypocretin neurotransmission participates in reinforcement processes, likely
      through modulation of the mesolimbic dopamine system. Additionally, the current
      observations suggest that the hypocretin system may provide a target for
      pharmacotherapies to treat cocaine addiction.

PMID- 20039961
TI  - The "repeater" phenomenon in migraine patients: a clinical and psychometric
      study.
AB  - BACKGROUND: Headache is one of the most common symptoms in an emergency
      department (ED), while migraine is the most frequently observed headache in this
      setting. The aim of our study was to evaluate the influence of clinical and
      psychometric variables on the repeater phenomenon, ie, patients who make at least
      3 visits to the ED at least 1 week apart during a 6-month period. METHODS:
      According to the International Classification of Headache Disorders, 2nd edition
      (ICHD-II) criteria, we consecutively recruited Italian-speaking migraine subjects
      who came to the ED or outpatient service. All the patients underwent the Migraine
      Disability Assessment Scale for the evaluation of migraine disability. We also
      administered the Beck Depression Inventory, State and Trait Anxiety Inventory,
      and Toronto Alexithymia Scale-20 for the evaluation of depressive, anxiety, and
      alexithymic symptoms, respectively. A personality profile was also obtained by
      means of the Tridimensional Personality Questionnaire (TPQ). RESULTS: We
      consecutively enrolled 465 migraine patients, diagnosed according to the ICHD-II
      criteria. Seventy (15%) of these patients met the repeater definition. The
      repeater group had more severe disability and was affected to a greater degree by
      chronic migraine, regardless of symptomatic drug overuse, than the non-repeater
      group. As regards the psychometric variables, repeaters were more alexithymic,
      anxious, and depressed than non-repeaters. The personality profile, as measured
      by the TPQ, revealed that the repeater patients scored higher on the harm
      avoidance scale and their subscales than the non-repeater patients. CONCLUSIONS:
      According to the findings of our study, the repeater migraineur is typically
      triptan-naive, more alexithymic, and more depressed than the non-repeater
      migraineur. A clinical and psychometric evaluation of repeater patients who go to
      the ED because of migraine attacks may help to understand this epidemiological
      and clinical phenomenon. From a clinical point of view, these psychometric
      findings may not only shed light on the epidemiology of migraine in the ED, but
      may also help to design a specific therapeutic protocol for this subgroup of
      migraine patients.

PMID- 20039962
TI  - The primary headaches as a reflection of genetic darwinian adaptive behavioral
      responses.
AB  - OBJECTIVE: The objective of this study is to present a view of the primary
      headaches as genetically determined behavioral responses consistent with sickness
      behavior and defense reaction, respectively. BACKGROUND AND DESIGN: A review of
      the literature bearing on the behavioral, humoral, and functional imaging aspects
      of the primary headaches shows that migraine and cluster headache (CH) are pain
      conditions characterized by different behaviors during the attacks. Here it is
      postulated that the behavioral responses to migraine and CH are evolutionary
      conserved reactions consistent with sickness behavior and defense reaction.
      RESULTS: The sickness behavior observed during migraine attacks is a pan
      mammalian adaptive response to internal and external stressors, characterized by
      withdrawal and motor quiescence, sympatho-inhibition and lethargy, in which
      visceral pain signals a homeostatic imbalance of the body and/or brain. In
      contrast, the defense reaction in CH consists of a fight-or-flight reaction, with
      motor restlessness and agitation, in which pain is exteroceptive in kind.
      CONCLUSION: These different behavioral responses are thus specific to different
      kinds of pain, distinguished by the behavioral significance of the pain (visceral
      pain in migraine vs exteroceptive pain in CH), and imply brain matrices involving
      different networks in the brainstem, hypothalamus, and forebrain regions that
      engender evolutionarily conserved adaptive genetic responses. Cytokines play an
      important role in their development. Predictions and limitations of the
      hypothesis are discussed together with implications for genetic studies on
      headaches.

PMID- 20039963
TI  - Headache: what do children and mothers expect from pediatricians?
AB  - BACKGROUND: Headache is a frequent occurrence among children and adolescents, and
      one of the most common causes of medical consultation. While serious conditions
      presenting headache as the chief complaint are not common in the pediatric
      population, enormous sums are invested to perform very expensive and often
      unnecessary diagnostic investigations. Pediatricians should adopt a flexible and
      diversified diagnostic/therapeutic approach and, at the same time, should not
      forget to take into consideration the demands, expectations, and worries of
      children and their parents. OBJECTIVE: The aim of this study was to assess
      simultaneously children's and mothers' expectations from the pediatric
      consultation concerning headache, and pediatricians' opinions about said
      expectations. In addition, we attempted to investigate mothers', children's, and
      pediatricians' opinions about symptomatic and prophylactic treatment of headache.
      METHOD: A total of 100 young headache sufferers, 50 were male and 50 were female,
      from 10 to 16 years of age, were enrolled in this study. Two diversified, self
      administered, ad hoc questionnaires about their expectations from the pediatric
      treatment of headache and about symptomatic and prophylactic treatment were
      delivered to each patient and their mother, to which they responded separately. A
      third self-administered questionnaire was delivered to a sample of 50
      pediatricians. RESULTS: Our study showed that children and their mothers
      sometimes have different expectations about the consultation of the pediatrician
      and of the headache specialist. Frequency of pain was the main reason for
      pediatric consultation for 70% of mothers, whereas only 2% of them (as opposed to
      what pediatricians believed) consulted the pediatrician because they were worried
      about a tumor. Moreover, a high percentage of children and mothers expected from
      the pediatric consultation to be reassured that it is not a serious illness and
      to find out the causes of headache (60% and 47%, and 45% and 62%, respectively).
      A total of 26% of children wanted to know the progression of headache in the
      future, but only 3% of mothers shared the same demand. With regard to their
      expectations, pediatricians agree only in part with children and their mothers.
      On the contrary, the majority of children (68%), mothers (49%), and pediatricians
      (90%) agree that a symptomatic treatment was necessary in the presence of a
      severe pain. In addition, 61% of children, 37% of mothers, and 74% of
      pediatricians believed that a prophylactic treatment was necessary when the pain
      is severe and long-lasting. CONCLUSION: Pediatricians sometimes do not consider
      sufficiently children's and mothers' wishes and expectations and, consequently,
      could limit the outcome of their diagnostic-therapeutic approach. This is
      particularly important because, in the developmental age, an accurate recognition
      of patients' and parents' expectations represents an essential requirement for a
      favorable outcome of the consultation.

PMID- 20039945
TI  - Prefrontal morphology, 5-HTTLPR polymorphism and biased attention for emotional
      stimuli.
AB  - Biased attention for emotional stimuli has been associated with vulnerability to
      psychopathology. This study examines the neural substrates of biased attention.
      Twenty-three adult women completed high-resolution structural imaging followed by
      a standard behavioral measure of biased attention (i.e. spatial cueing task).
      Participants were also genotyped for the serotonin transporter-linked promoter
      region (5-HTTLPR) gene. Results indicated that lateral prefrontal cortex (lPFC)
      morphology was inversely associated with maintained attention for positive and
      negative stimuli, but only among short 5-HTTLPR allele carriers. No such
      associations were observed for the medial prefrontal cortex (mPFC) or the
      amygdala. Results from this study suggest that brain regions involved in
      cognitive control of emotion are also associated with attentional biases for
      emotion stimuli among short 5-HTTLPR allele carriers.

PMID- 20039955
TI  - Medication-overuse headache and personality: a controlled study by means of the
      MMPI-2.
AB  - OBJECTIVE: The main aim of this study involves comparing the personality profiles
      of patients with medication-overuse headache (MOH) and episodic headaches, in
      order to elucidate the role of personality characteristics, according to one of
      the most widely used and validated personality assessment tool: Minnesota
      Multiphasic Personality Inventory (MMPI-2). BACKGROUND: Many studies have
      assessed the personality of headache patients by means of MMPI-2 only using
      clinical and content scales. In this study the supplementary scales were also
      used as they evaluate different aspects of personality, particularly broad
      personality characteristics, generalized emotional distress and behavioral
      dyscontrol. METHODS: We recruited 219 subjects (151 women and 68 men) who were
      grouped in the following categories: MOH group (n = 82); episodic headache group
      (n = 82; 58 migraine aura; 6 migraine with aura; 6 frequent episodic tension-type
      headache; 12 migraine+infrequent episodic tension-type headache) and 1 group of
      55 healthy controls. MMPI-2 was employed. Data were computed with one-way anova
      and post hoc analyses. RESULTS: Medication-overuse headache and episodic headache
      patients (EH) showed a very similar pattern, differentiating each other only in
      the Hypochondriasis (Hs) (P = .007; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD
      5.88] and Health Concerns [HEA]) (P = .005; MOH: mean 14.06 [SD 5.38]; EH: mean
      11.81 [SD 5.59]) scales. Surprisingly, no differences were found between the 3
      groups in the scales measuring dependence-related behavior such as Addiction
      Potential Scale (Aps) and Addiction Admission Scale (Aas). MOH and episodic
      headache patients scored significantly higher in the so-called neurotic scales Hs
      (P < .0001; MOH: mean 14.18 [SD 5.53]; EH: mean 11.93 [SD 5.88]; CONTROLS: mean
      5.91 [SD 3.57]), Depression (D) (P < .0001; MOH: mean 26.44 [SD 7.01]; EH: mean
      26.09 [SD 5.85]; CONTROLS: mean 21.47 [SD 4.90]), and Hysteria (Hy) (P < .0001;
      MOH: mean 27.33 [SD 5.51]; EH: mean 26.81 [SD 5.68]; CONTROLS: mean 21.95 [3.85])
      and in many other scales such as Paranoia (Pa), Psychasthenia (Pt), Schizophrenia
      (Sc) while they scored significantly lower on Ego Strength (Es) and Dominance
      (Do) scales when compared with controls. CONCLUSIONS: Patients with MOH and
      episodic headache showed very similar patterns, differentiating only in the
      Hypochondriasis and Health Concerns scales. Surprisingly, there were no
      significant differences in the scores of the scales measuring dependence-related
      behavior. The clinical role of MMPI-2 in discriminating MOH patients with
      dependency from drugs is discussed, in order to implement a complete tests'
      battery for headache patients' assessment.

PMID- 20039966
TI  - It's not just about heart failure--voices of older people in transition to
      dependence and death.
AB  - This paper explores the experiences of older people living with heart failure and
      their transitions from independence to dependence and for some death. New
      Zealand's ageing population is predicted to increase from 12% in 2001 to 25% by
      the year 2051, similar to the worldwide trend of ageing. A high proportion of
      these people will have one or more chronic illnesses. Associated with the
      increase in survival is a growing body of research examining the needs of the
      older person with heart failure and finding particular problems with end of life
      care. Older people face many challenges in living with their heart failure, in
      particular the transition to dependence. To study the transition a longitudinal
      qualitative study using General Inductive approach was used. Participants were
      interviewed every 3 months for a 12-month period during 2006-2008. A total of 79
      interviews with 25 people were completed. Our findings showed that transition was
      not a simple linear process with the older person moving from one phase to
      another; instead their experiences illustrated the complexity of transitions they
      faced and what helped them to manage these. The older people in this study
      illustrated the importance of trust in health professionals and believed they
      would receive good care. Their fears revealed concerns about being a burden as
      they deteriorate and becoming more dependent. Understanding the complex issues
      related to transition to dependence can provide health professionals with a
      framework for assessment and approaches to providing the support required.

PMID- 20039967
TI  - Developing world class commissioning competencies in care services in England:
      the role of the service improvement agency.
AB  - This article provides an insight into the support needs of health and social care
      commissioners seeking to develop world class commissioning competencies and the
      role of service improvement agencies in meeting these needs. Reporting findings
      from the evaluation of one service improvement agency based in England, we focus
      on the 'improvement supports' (the products and services) that were delivered by
      the 'Care Services Improvement Partnership' through its 'Better Commissioning
      Programme'. In-depth interviews were carried out with 25 care commissioners (n =
      25) exploring how the Programme was used in their day to day work, its perceived
      value and limitations. Given the lack of employer-led training and induction we
      conclude that service improvement agencies play an important role in developing
      commissioners' skills and competencies. However, we suggest that achieving world
      class commissioning may depend on a more fundamental rethink of commissioning
      organisations' approaches to learning and development.

PMID- 20039969
TI  - 'You opened our eyes': care-giving after learning a child's positive HIV status
      in rural South Africa.
AB  - Caregivers of young children identified as HIV positive, residing in Agincourt,
      rural South Africa were advised of their child's status. How was this knowledge
      received, and how did it influence care-giving and support? Interviews were
      conducted in May to June 2008 with caregivers of HIV positive children aged 1-5
      years, 1 year following the child's HIV test and disclosure of status. Drawing on
      data from 31 semi-structured questionnaires and 21 in-depth interviews, we
      describe caregivers' attitudes, reactions, fears and aspirations after learning a
      child's HIV status, the perceived usefulness of the knowledge, barriers to care
      giving and support received. Sociodemographic data collected through the
      questionnaire were analysed using Stata. Qualitative data were coded in NVIVO 8
      and analysed inductively to identify themes and their repetitions and variations.
      Although almost half of the caregivers responded negatively initially, 1 year
      later, almost all had accepted and valued knowing their child's HIV status as
      this had enhanced their competency in care-giving. Counselling from health
      providers and personal spirituality helped caregivers to accept the child's
      status and cope with its implications. Most caregivers had high aspirations for
      the child's future, despite some expressed difficulties associated with care
      giving, including financial constraints, information gaps and barriers to
      healthcare. The results indicate an opportunity for paediatric HIV screening in
      communities with high HIV prevalence. This would facilitate early uptake of
      available interventions, so enhancing the survival of HIV positive children.

PMID- 20039971
TI  - Structural complexity of the testis and PKG I / StAR interaction regulate the
      Leydig cell adaptive response to repeated immobilization stress.
AB  - The role of the structural complexity of the testis and the nitric oxide (NO)
      cyclic guanosine monophosphate (cGMP) signalling pathway was analysed in adult
      male rats exposed to acute and repeated immobilization stress (IMO). In whole
      testis preparations, exposure to acute and repeated IMO caused an increase in NO
      production. In contrast, NO production was inhibited in interstitial cell
      preparations after exposure to all types of stress. In purified Leydig cell
      preparations, NO production was inhibited only after exposure to prolonged IMO.
      These findings indicate that biologically active compounds released from various
      testicular compartments exert both stimulatory and inhibitory effects on NO
      production. TaqMan Low Density Array of rat phosphodiesterases revealed a
      decrease in the expression of cGMP-specific phosphodiesterase 5 (PDE5) in Leydig
      cells of animals exposed to repeated IMO. In contrast, the expression of cGMP
      dependent protein kinase type I (PKG I), total and phosphorylated steroidogenic
      acute regulatory protein (StAR), and PKG I/StAR immunoprecipitated complex was
      increased during repeated exposure to IMO. The increase in both total and
      phosphorylated StAR formation was effectively blocked by inhibition of PKG I in
      vitro. Thus, increased expressions of PKG I and StAR complex, accompanied by
      decreased PDE5 activity, suggest that the NO-cGMP signalling pathway and
      consequent activation of the StAR protein regulate the adaptive response of
      Leydig cells to repeated IMO stress.

PMID- 20039968
TI  - Barriers to dying at home: the impact of poor co-ordination of community service
      provision for patients with cancer.
AB  - For patients dying of cancer, there is an emphasis on giving choice regarding
      preferred location for care, with the option of dying at home, which is integral
      to UK government health initiatives such as the End of Life Care Programme.
      However, patients continue to be admitted to hospital in the terminal phase of
      their illness when they have expressed a desire to die at home. A qualitative
      study, using two audio tape-recorded focus group interviews, with a purposive
      sample of district nurses and community specialist palliative care nurses (19)
      was undertaken across two primary care trusts in the north west of England. Data
      were analysed using a thematic analysis approach. From a service provision
      perspective, the results reveal that poor discharge planning and co-ordination,
      difficulty in establishing additional equipment and services together with
      inadequate out of hours medical provision were all factors contributing to
      hospital admissions for patients with cancer in the last hours and days of life,
      and thus were barriers to dying at home.

PMID- 20039970
TI  - What do women gain from volunteering? The experience of lay Arab and Jewish women
      volunteers in the Women for Women's Health programme in Israel.
AB  - Ambiguous feelings regarding women engaging in formal volunteering and concerns
      about their exploitation might explain the dearth of studies regarding the
      volunteering benefits specifically experienced by low socioeconomic status women.
      The current study examined benefits of volunteering among women participating in
      Women for Women's Health (WWH), a lay health volunteers (LHV) programme
      implemented in Jewish and Arab communities in Israel, and aiming at empowering
      such women to become active volunteers and promote health activities in their
      communities. Two years after the introduction of WWH in each community, all 45
      Jewish and 25 Arab volunteers were contacted by phone and invited to participate
      in the focus group discussions. Five focus group discussions were conducted with
      25/42 Jewish volunteers in 2003 and four with 20/25 Arab volunteers in 2005. The
      other volunteers could not attend the scheduled meetings or became inactive for
      personal reasons. Four benefit categories were identified in both ethnic groups:
      1. Personal benefits of having increased knowledge, feeling self-satisfaction,
      mastering new skills and performing healthy behaviours; 2. Group-social benefits
      of social support and sense of cohesion; 3. Purposive benefits of achieving the
      WWH mission and goals; 4. Sociopolitical benefits of learning to accept the other
      and experiencing increased solidarity. However, the relatively less privileged
      Arab volunteers enumerated more benefits within the personal and purposive
      categories. They also identified the unique sociocultural category of improving
      women's status in the community by creating a legitimate space for women by
      public sphere involvement, traditionally solely a male domain. We conclude that
      volunteering in community-based health promotion programmes can be an empowering
      experience for lay women without being exploitative. Positive volunteering
      benefits will be even more discernable among underprivileged women who enjoy
      fewer opportunities in the personal and public domains. More studies need to
      explore volunteering benefits as reported by LHVs, making these benefits more
      visible and desirable.

PMID- 20039972
TI  - Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed
      after gastric bypass surgery: a prospective randomized controlled trial.
AB  - The effects of weight loss on erectile function and hormones have not been well
      studied. The aim of this study was to measure the degree to which sexual function
      and in particular erectile function and hormonal environment change after
      substantial weight loss, surgically and non-surgically induced in the morbidly
      obese male in a prospective randomized long-term controlled trial. Furthermore,
      how surgery makes a difference when treating morbidly obese men was envisaged in
      this context. We prospectively studied 20 morbidly obese men for 24 months,
      divided into two groups: group A included 10 patients who underwent life style
      modifications (exercise and diet) for 4 months and subsequently gastric bypass,
      and another 10 patients in group B were kept on weekly follow-up. None of the men
      were taking phosphodiesterase type-5 inhibitors. All patients underwent
      International Index of Erectile Function (IIEF)-5 questionnaire, serum
      oestradiol, prolactin (PRL), luteinizing (LH) and follicle-stimulating (FSH)
      hormones, free and total testosterone (FT and TT) at baseline (time 0), surgery -
      4 months latter baseline (time 1) and final evaluation - 24 months (time 2). From
      times 0 to 1, group A presented a mean body mass index (BMI) reduction of 12.6 (p
      < 0.0001), whereas group B, 2.1 (p > 0.05). The BMI reductions between times 0
      and 2 were 24.7 (p < 0.0001) and 0.7 (p > 0.05) for groups A and B respectively.
      BMI average between the two groups was similar at time 0 (p = 0.2142), and
      different at times 1 (p = 0.0033) and 2 (p < 0.0006). Increase in IIEF-5 score (p
      = 0.0469), TT (p = 0.0349) and FSH levels (p = 0.0025), and reduction in PRL
      level (p < 0.0001) were observed in group A from times 0 to 2 and 1 to 2. There
      were no changes from times 0 to 1. Comparing groups A and B at time 2, IIEF-5, TT
      and FT increased significantly in group A (p = 0.0224, 0.0043 and 0.0149
      respectively). Surgery-induced weight loss increased erectile function quality
      measured by IIEF-5 questionnaire, increased TT, FT and FSH and reduced PRL
      levels. The hormonal impact verified could justify the improvement in erectile
      function. Lifestyle modifications impacted BMI without hormonal or sexual impact
      in morbidly obese. New studies are warranted in the field to support our data.

PMID- 20039973
TI  - Differential effect of specific gr/gr deletion subtypes on spermatogenesis in the
      Chinese Han population.
AB  - As a common variation in the azoospermia factor c (AZFc) region of Y chromosome,
      the gr/gr deletion is regarded as a significant risk factor for spermatogenic
      impairment, whereas the association of the deletion's phenotypic expression with
      Y-chromosomal background is still a subject of debate. To further investigate the
      contribution of the deletion to spermatogenic impairment in different Y
      chromosomal haplogroups, the partial AZFc deletion was detected with AZFc
      specific sequence tagged sites, gene dosage and gene copy analyses of deleted in
      azoospermia (DAZ), chromodomain Y1 (CDY1) and basic protein Y2 (BPY2) in 1426
      azoo/oligozoospermic and 672 normozoospermic men from a Chinese population. The
      haplogrouping was performed in 231 deletion carriers with 12 polymorphic loci of
      Y chromosome. As a result, five gr/gr rearrangement types in eight Y haplogroups
      were observed, in which the simple gr/gr deletion was the most common type, and
      its frequency was significantly higher in men with azoo/oligozoospermia relative
      to normozoospermia. Also the distribution of gr/gr-rearranged Y haplogroups was
      significantly different between the two groups, in which gr/gr-deleted
      haplogroups C and DE were more common in men with azoo/oligozoospermia. In the 6
      gr/gr copy deletion haplotypes, the frequencies of DAZ1/DAZ2+CDY1a or CDY1b
      deletion were significantly higher in men with azoo/oligozoospermia, while all
      DAZ3/DAZ4+CDY1b+BPY2.2 or 2.3 deletions were found only in haplogroup Q1 without
      any distribution difference between the azoo/oligozoospermic and normozoospermic
      groups. This study provided further evidence for the existence of multiple
      subtypes of gr/gr deletion and indicates that gr/gr-DAZ1/DAZ2 deletion is a
      significant risk factor. However, the association of the phenotypic variation of
      gr/gr deletion with Y-chromosomal haplogroups is not definite yet, because of the
      limited amounts of the deletions observed in each of the haplogroups and the lack
      of the quantitative trait analyses such as sperm density analysis. The fact that
      a common gr/gr copy deletion haplotype was found exclusively in the Y hgr Q1,
      without pathogenic consequences, implies the importance of haplogrouping and of
      copy deletion typing prior to genetic counselling of deletion carriers of Chinese
      descent.

PMID- 20039974
TI  - Impact of prior or concomitant seasonal influenza vaccination on MF59-adjuvanted
      H1N1v vaccine (Focetria) in adult and elderly subjects.
AB  - BACKGROUND: When H1N1v vaccines become widely available, most elderly subjects
      will have already received their seasonal influenza vaccination. Adults seeking
      H1N1v vaccination may be offered seasonal vaccine as well. We investigated prior
      seasonal vaccination in adult and elderly subjects, and concomitant vaccination
      with seasonal vaccine in adults, on the tolerability and immunogenicity of the
      Novartis MF59-adjuvanted H1N1v vaccine, Focetria. METHODS: A total of 264 adult
      (four groups) and 154 elderly (three groups) subjects were enrolled. The
      licensure study cohorts for plain (Agrippal) and MF59-adjuvanted (Fluad) 2009
      2010 seasonal vaccines were invited to receive Focetria 3 months later, with
      seasonal vaccine-naive controls, and adults who received Focteria and seasonal
      vaccine concomitantly. Immunogenicity of all vaccines was assessed by
      haemagglutination inhibition on Days 1 and 22, safety and reactogenicity were
      monitored using patient diaries. RESULTS: All adult and elderly groups met all
      the European CHMP licensing criteria for H1N1v, as did adults receiving
      concomitant seasonal vaccine for the three seasonal strains. Vaccines were
      generally well tolerated, causing no SAEs, and profiles typical of MF59
      adjuvanted vaccines. Reactions were mainly mild or moderate and transient, and
      unaffected by prior or concomitant seasonal vaccination except for elderly
      subjects previously given MF59-adjuvanted seasonal vaccine, whose reaction rates
      to Focetria were about half those seen in groups receiving their first MF59
      vaccine. CONCLUSION: One dose of MF59-adjuvanted H1N1v vaccine met the licensure
      criteria for adult and elderly subjects 3 months after seasonal vaccination, or
      concomitantly with seasonal vaccine in adults, without impacting the tolerability
      or immunogenicity of either vaccine, thus facilitating mass influenza
      immunisation campaigns.

PMID- 20039975
TI  - STEP: simplified treatment of the enlarged prostate.
AB  - We propose a simple and practical approach to the identification, evaluation and
      treatment of lower urinary tract symptoms (LUTS) resulting from an enlarging and
      obstructive prostate. The proposed Simplified Treatment for Enlarged Prostate
      (STEP) plan is a logical guide to patient management by the primary care provider
      (PCP). Symptoms of enlarged prostate (EP) are common and may frequently progress
      into a condition with profound adverse effects on quality of life. Despite the
      high prevalence, EP is underdiagnosed and undertreated. This situation may result
      from patient- and provider-related issues. Assessment of symptoms of EP should be
      initiated with a discussion of LUTS. Evaluation includes a focused history,
      physical examination and selected laboratory tests. Certain factors put the
      symptomatic patient at risk for disease progression; however, not all factors can
      be readily evaluated in the PCP setting. The serum prostate-specific antigen
      (PSA) level acts both as an indicator of prostatic size and a screening tool for
      prostatic cancer, and thereby provides an important tool for PCPs. The STEP plan
      is a logical guide to patient management. Step 1, watchful waiting, is
      appropriate in patients with symptoms that are not bothersome. If symptoms cause
      bother, the initiation of an alpha-blocker (AB) in step 2, provides relatively
      rapid symptom improvement. Patients with bothersome symptoms and a PSA > or = 1.5
      ng/ml are at risk for progression and consideration should be given to
      combination treatment with an AB and a 5alpha-reductase inhibitor (step 3).
      Patients with refractory symptoms should be referred to a urologist (step 4).
      Identification, evaluation and management of EP are within the domain of the
      primary care setting. The STEP approach provides a simple and practical framework
      for PCPs to manage most men with symptoms of EP.

PMID- 20039976
TI  - Health-related quality of life in men with localized prostate cancer.
AB  - With the established effectiveness of diverse treatments for localized prostate
      cancer, the identification of the physical and psychological consequences of the
      disease and its various treatments has become critical. In the present review, we
      aim to familiarize the reader with the methodologies of health-related quality of
      life (HRQOL) research and to review the recent literature on HRQOL outcomes in
      patients with localized prostate cancer. Studies have shown that prostate cancer
      and its treatment affect both disease-specific HRQOL (i.e. urinary, sexual, and
      bowel function) as well as general HRQOL (i.e. energy/vitality and performance in
      physical and social roles). However, these effects appear to differ according to
      the type of treatment, stage of disease, age of the subjects, time after
      treatment, and, more importantly, race or ethnicity. By including HRQOL in
      clinical decision-making, we can help our patients make more informed treatment
      choices for localized prostate cancer.

PMID- 20039977
TI  - Deep evolutionary roots of strepsirrhine primate labyrinthine morphology.
AB  - The cavity system of the inner ear of mammals is a complex three-dimensional
      structure that houses the organs of equilibrium and hearing. Morphological
      variation of the inner ear across mammals reflects differences in locomotor
      behaviour and hearing performance, and the good preservation of this structure in
      many fossil specimens permits analogous inferences. However, it is less well
      known to what extent the morphology of the bony labyrinth conveys information
      about the evolutionary history of primate taxa. We studied this question in
      strepsirrhine primates with the aim to assess the potential and limitations of
      using the inner ear as a phylogenetic marker. Geometric morphometric analysis
      showed that the labyrinthine morphology of extant strepsirrhines contains a mixed
      locomotor, allometric and phylogenetic signal. Discriminant analysis at the
      family level confirmed that labyrinthine shape is a good taxonomic marker. Our
      results support the hypothesis that evolutionary change in labyrinthine
      morphology is adequately described with a random walk model, i.e. random
      phenotypic dispersal in morphospace. Under this hypothesis, average shapes
      calculated for each node of the phylogenetic tree give an estimate of inner ear
      shapes of the respective last common ancestors (LCAs), and this information can
      be used to infer character state polarity. The labyrinthine morphology of the
      fossil Adapinae is close to the inferred basal morphology of the strepsirrhines.
      The inner ear of Daubentonia, one of the most derived extant strepsirrhines, is
      autapomorphic in many respects, but also presents unique similarities with
      adapine labyrinths.

PMID- 20039978
TI  - Prediction equations for human thoracic and lumbar vertebral morphometry.
AB  - Statistical correlations between anatomical dimensions of human vertebral
      structures have indicated a potential for the prediction of vertebral
      morphometry, which could be applied to the creation of simplified geometrical
      models of the spine excluding the need for preliminary processing of medical
      images. The aim of this study was to perform linear and nonlinear regressions
      with published anatomical data to generate prediction equations for 20 vertebral
      parameters of the human thoracic and lumbar spine as a function of only one given
      parameter that was measured by X-ray. Each parameter was considered individually
      as a potential predictor variable in terms of its correlation with all of the
      other parameters, together with the readiness with which lateral X-rays could be
      obtained. Based on this, the parameter vertebral body height posterior was chosen
      and the statistical analyses described here are related to this parameter. Our
      linear, exponential and logarithmic regressions provided significant predictions
      of anterior vertebral structures. However, third-order polynomial prediction
      equations allowed an improvement on these predictions (P-values < 0.001), e.g.
      endplates and spinal canal (R(2), 0.970-0.995) as well as pedicle heights and the
      spinous process (R(2), 0.811-0.882), in addition to a reasonable prediction of
      the posterior vertebral structures, which have shown a low or no correlation in
      previous studies, e.g. pedicle inclination and transverse process (R(2), 0.514
      0.693) (anova). Comparisons of the theoretical predictions with two other sets of
      experimental data indicated that the predictions generally agree well with the
      experimental data. A time-efficient approach for obtaining anatomical data for
      the description of human thoracic and lumbar geometry was provided by this
      method, which requires the measurement of only one parameter per vertebra
      (vertebral body height posterior) from a lateral X-ray and the set of developed
      prediction equations. Vertebral models based on this type of parameterized
      geometry could be used in biomechanical studies that require geometry variation,
      such as in spinal deformations, including scoliosis.

PMID- 20039979
TI  - Functional anatomy of the forelimb in Promegantereon* ogygia (Felidae,
      Machairodontinae, Smilodontini) from the late miocene of spain and the origins of
      the sabre-toothed felid model.
AB  - We examine the functional anatomy of the forelimb in the primitive sabre-toothed
      cat Promegantereon ogygia in comparison with that of the extant pantherins, other
      felids and canids. The study reveals that this early machairodontine had already
      developed strong forelimbs and a short and robust thumb, a combination that
      probably allowed P. ogygia to exert relatively greater forces than extant
      pantherins. These features can be clearly related to the evolution of the sabre
      toothed cat hunting method, in which the rapid killing of prey was achieved with
      a precise canine shear-bite to the throat. In this early sabre-toothed cat from
      the Late Miocene, the strong forelimbs and thumb were adapted to achieve the
      rapid immobilization of prey, thus decreasing the risk of injury and minimizing
      energy expenditure. We suggest that these were the major evolutionary pressures
      that led to the appearance of the sabre-toothed cat model from the primitive
      forms of the Middle Miocene, rather than the hunting of very large prey, although
      these adaptations reached their highest development in the more advanced sabre
      toothed cats of the Plio-Pleistocene, such as Smilodon and Homotherium. Although
      having very different body proportions, these later animals developed such
      extremely powerful forelimbs that they were probably able to capture relatively
      larger prey than extant pantherins.

PMID- 20039981
TI  - Estimating terrestrial contribution to stream invertebrates and periphyton using
      a gradient-based mixing model for delta13C.
AB  - 1. This paper outlines a gradient-based model that can be used for isotopic
      signature source partitioning, even if source signatures are not distinct, as
      long as their spatial gradients differ. A model of this type is applied to the
      partitioning of autochthonous vs. allochthonous contribution to stream
      invertebrate delta(13)C signatures, which has often been confounded by overlap in
      source signatures. 2. delta(13)C signatures of inorganic carbon and most
      autochthonous production exhibit pronounced gradients along rivers, being
      depleted relative to terrestrial signatures in upstream reaches, and enriched
      downstream. Terrestrial detritus, by contrast, exhibits no gradient. Thus
      terrestrial food consumption reduces downstream signature slopes in proportion to
      the amount of terrestrial food consumed. 3. The gradient-based mixing model
      produces estimates of the proportion of terrestrial consumption (p(T)) from
      signature slopes of consumers; p(T) estimates for invertebrate primary consumers
      were: herbivore/grazers (0.15) <filterers (0.38), collector/gatherers (0.43)
      <shredders (0.85). 4. Periphyton (epilithon), a mixture of attached algae,
      bacteria and detritus, exhibited a weaker downstream slope than attached algae.
      p(T) values calculated for periphyton relative to pure algal signatures were 0.32
      implying approximately 30% allochthonous content. The slope for herbivore/grazers
      calculated relative to periphyton signatures was >1, indicating selective
      assimilation of the autochthonous component from the biofilms.

PMID- 20039982
TI  - Large herbivores facilitate savanna tree establishment via diverse and indirect
      pathways.
AB  - 1. Savanna ecosystems are defined largely by tree-grass mixtures, and tree
      establishment is a key driver of community structure and ecosystem function in
      these systems. The factors controlling savanna tree establishment are
      understudied, but likely involve some combination of seed, microsite and
      predator/fire limitation. In African savannas, suppression and killing of adult
      trees by large mammals like elephants (Loxodonta africana Blumenbach, 1797) and
      giraffes (Giraffa camelopardalis Linnaeus, 1758) can maintain tree-grass co
      dominance, although the impacts of even these conspicuous herbivores on tree
      establishment also are poorly understood. 2. We combined seed addition and
      predator exclusion experiments with a large-scale, long-term field manipulation
      of large herbivores to investigate the relative importance of seeds, microsites
      and predators in limiting establishment of a monodominant tree (Acacia
      drepanolobium Sjostedt) in a Kenyan savanna. 3. Both wild and domestic (i.e.
      cattle; Bos taurus Linnaeus, 1758) large herbivores facilitated tree
      establishment by suppressing abundances of rodents, the most important seed and
      seedling predators. However, this indirect, positive effect of wild herbivores
      was negated by wild herbivores' suppression of seed production. Cattle did not
      have this direct, negative impact; rather, they further assisted tree
      establishment by reducing cover of understorey grasses. Thus, the impacts of both
      groups of large herbivores on tree establishment were largely routed through
      other taxa, with a negligible net effect of wild herbivores and a positive net
      effect of cattle on tree establishment. 4. The distinction between the (positive)
      net effect of cattle and (neutral) net effect of wild herbivores is due to the
      inclusion of browsers and mixed feeders within the assemblage of wild herbivores.
      Browsing by wild herbivores limited seed production, which reduced tree
      recruitment; grazing by cattle was more pronounced than that by wild herbivores,
      and thus promoted germination and subsequent establishment of small trees. 5. Our
      study is the first to link seed fates to tree establishment in savanna ecosystems
      in experimentally-manipulated herbivore communities. Further, our results
      highlight how large herbivores can modify a suite of independent factors - seed
      production, competition with understorey species, and seed and seedling predation
      - to collectively drive tree establishment.

PMID- 20039983
TI  - Anterior aortic reimplantation of anomalous left coronary artery from the
      pulmonary artery (ALCAPA) originating from the nonfacing sinus in an adult.
AB  - We report successful repair of a rare type of anomalous origin left main coronary
      artery from the nonfacing pulmonary artery sinus in an adult patient presenting
      with cardiac arrest as first symptom. Intraoperative findings and surgical
      technique are discussed.

PMID- 20039984
TI  - Double barrel reconstruction of the right ventricular outflow tract.

PMID- 20039985
TI  - Coronary-coronary bypass grafting to reduce the risk of aortic atheroembolism.
AB  - Coronary-coronary bypass grafting refers to making anastomoses between two
      segments of the same coronary artery or between different coronary arteries, and
      provides less "touch" to the aorta, which is important for the patients with
      severely atherosclerotic ascending aorta. In this report we represent a case of a
      patient with extensive atherosclerotic aorta, in whom a saphenous vein graft was
      placed between the acute marginal and the posterior-descending branches of the
      right coronary artery during an off-pump coronary artery bypass grafting surgery.

PMID- 20039986
TI  - Mechanical support for patients with end-stage heart failure during noncardiac
      surgical procedures.

PMID- 20039987
TI  - A case of focal atrial tachycardia from the aortomitral continuity.

PMID- 20039988
TI  - Septal ventricular tachycardia with alternating LBBB-RBBB morphology in isolated
      ventricular noncompaction.
AB  - Knowledge on ventricular tachycardia (VT) in isolated ventricular noncompaction
      (IVNC) is limited. We report on a patient with IVNC who presented with
      cardiogenic shock due to an incessant drug-resistant VT that was cured by
      radiofrequency ablation. The VT had characteristics of a deep septal focal
      arrhythmia, which was distinctive by ablation-induced alternation of the
      rightward and leftward exits, and was difficult to ablate from either side of the
      ventricular septum.

PMID- 20039989
TI  - Use of the Impella microaxial blood pump for ablation of hemodynamically unstable
      ventricular tachycardia.
AB  - Ablation for ventricular tachycardia remains a challenge with suboptimal
      procedural success rates. One of the major causes of difficulty is precipitous
      hypotension when ventricular tachycardia is induced precluding even rapid mapping
      of the arrhythmia. We report the successful use of the Impella microcirculatory
      axial blood flow pump in 3 patients with hemodynamically unstable ventricular
      tachycardia that allowed successful completion of the procedure. In these 3
      patients, there was no evidence of Impella-related valvular disturbance,
      iatrogenic ventricular arrhythmias, or interference with mapping and ablation
      catheter movement.

PMID- 20039990
TI  - On the use of CartoSound for left atrial navigation.
AB  - INTRODUCTION: The utility of "virtual" imaging systems for left atrial (LA)
      navigation has been hampered by inadequate spatial detail, as well as inaccurate
      integration of more detailed preoperative images, such as those generated by
      computed tomography (CT). CartoSound is an intracardiac echocardiography (ICE)
      based technology that promises to ameliorate these problems. Our objective was to
      examine the capabilities and optimal use of CartoSound, both as a stand-alone
      tool and as a facilitator of CT image integration. METHODS AND RESULTS: In 10
      patients, CartoSound models of the LA were generated using each of 4 ICE
      transducer locations: LA, right atrium (RA), coronary sinus (CS), and esophagus
      (ESO). Each of these models was used to register CT-derived LA models into the
      operative workspace. We correlated the comprehensiveness of LA imaging from each
      transducer location with the quality of the CT registration, as well as the
      accuracy of mock circumferential antral ablation guided by the CartoSound model
      alone or by the CT model. The LA transducer location provided the most
      comprehensive rendering of the LA, which was associated with higher quality CT
      registration and greater CT-guided mock ablation accuracy. Mock ablation guided
      by the CartoSound model alone was at least as accurate as CT, although the models
      were less intuitive. CONCLUSIONS: For LA navigation, optimal use of CartoSound
      may require LA transducer location, which is effective for stand-alone use and as
      a facilitator of CT image integration.

PMID- 20039991
TI  - Intraprocedural use of ibutilide to organize and guide ablation of complex
      fractionated atrial electrograms: preliminary assessment of a modified step-wise
      approach to ablation of persistent atrial fibrillation.
AB  - INTRODUCTION: While able to achieve clinical success, the current step-wise
      approach to persistent atrial fibrillation (AF) ablation requires considerable
      "substrate" ablation and frequently mandates multiple procedures to address
      consequent atrial tachycardias (ATs). An alternative strategy minimizing the
      amount of ablation while maintaining clinical success would be desirable. We
      hypothesize that intraprocedural administration of a low-dose antiarrhythmic drug
      (AAD) during AF will organize areas of passive activation and not affect areas
      critical to AF maintenance, thereby potentially minimizing the ablation lesion
      set. METHODS AND RESULTS: Eleven patients (age = 55 +/- 6 years; LA = 48 +/- 15
      mm; median AF duration = 3 years) with persistent AF undergoing catheter ablation
      were enrolled in this exploratory prospective observational study. After
      pulmonary vein (PV) isolation, a mean cycle length (mCL) map was created and
      areas with mCL <120 ms were considered to represent complex fractionated atrial
      electrograms (CFAE). Ibutilide (0.25-1.0 mg) was then administered and a second
      mCL map created. Ablation lesions were placed at CAFE sites identified after
      ibutilide administration. Activation and/or entrainment mapping was employed to
      address ATs. The endpoint of ablation was achieving sinus rhythm. The average LA
      mCL increased (146 vs 165 ms, P = 0.01) and the LA CFAE surface area decreased
      after ibutilide administration. Additional ablation organized AF to either sinus
      rhythm or AT in 10/11 (91%) patients. After a median follow up of 455 days, 8 of
      11 (72%) patients were free from AF. Three patients underwent a repeat ablation
      procedure (average 1.27 ablations/patient). CONCLUSIONS: Ibutilide administration
      may organize atrial activity and facilitate AF termination during ablation while
      minimizing the ablation lesion set.

PMID- 20039992
TI  - Safety and convenience of continuous warfarin strategy during the periprocedural
      period in patients who underwent catheter ablation of atrial fibrillation.
AB  - BACKGROUND: We investigated the efficiency and convenience of a continuous
      warfarinization (CW) strategy during the periprocedural period of radiofrequency
      catheter ablation (RFCA) of atrial fibrillation (AF) in comparison with the
      classic strategy of switching to heparin (SH). METHODS AND RESULTS: We compared
      CW (n = 49) and SH (n = 55, 3 days before RFCA) in 104 patients who underwent
      RFCA of AF (77 males, 55 +/- 12 years old, paroxysmal AF: persistent AF = 63:41).
      During the procedure, the activated clotting time (ACT) was maintained between
      350 and 400 seconds, and a requirement of H, postablation INR, and periprocedural
      complications were compared. Results were as follows: (1) in the CW group, the
      preprocedural INR (1.85 +/- 0.61 vs 1.05 +/- 0.12, P < 0.001) and the proportions
      of INR > 2.0 after RFCA (1st postprocedure day 61.2% vs 5.5%, P < 0.001; 2nd
      postprocedure day 83.3% vs 21.8%, P < 0.005) were higher, and the heparin
      requirement was lower (2012 +/- 998 U/30 minutes vs 2921 +/- 795 U/30 minutes, P
      < 0.001) than in the SH group. (2) The incidences of hemorrhagic complications
      (18.2% vs 18.4%, P = NS) or the major bleeding rates (reduced hemoglobin >or= 4
      g/dL, requiring blood transfusion; 3.6% vs 12.2%, P = NS) were not significantly
      different in the CW group than in the SH group. CONCLUSION: The periprocedural CW
      strategy maintains a more stable INR immediately after AF ablation without
      increasing hemorrhagic complications compared with the classic strategy of SH.
      Simple CW can replace SH in an experienced laboratory with a low risk of
      hemopericardium during AF ablation.

PMID- 20039993
TI  - Linear ablation of right atrial free wall flutter: demonstration of bidirectional
      conduction block as an endpoint associated with long-term success.
AB  - INTRODUCTION: Ablation for atypical atrial flutter (AFL) is often performed
      during tachycardia, with termination or noninducibility of AFL as the endpoint.
      Termination alone is, however, an inadequate endpoint for typical AFL ablation,
      where incomplete isthmus block leads to high recurrence rates. We assessed
      conduction block across a low lateral right atrial (RA) ablation line (LRA) from
      free wall scar to the inferior vena cava (IVC) or tricuspid annulus in 11
      consecutive patients with atypical RA free wall flutter. METHOD AND RESULTS: LRA
      block was assessed following termination of AFL, by pacing from the ablation
      catheter in the low lateral RA posterior to the ablation line and recording the
      sequence and timing of activation anterior to the line with a duodecapole
      catheter, and vice versa for bidirectional block. LRA block resulted in a high to
      low activation pattern on the halo and a mean conduction time of 201 +/- 48 ms to
      distal halo. LRA conduction block was present in only 2 out of 6 patients after
      termination of AFL by ablation. Ablation was performed during sinus rhythm (SR)
      in 9 patients to achieve LRA conduction block. No recurrence of AFL was observed
      at long-term follow-up (22 +/- 12 months); 3 patients developed AF. CONCLUSION:
      Termination of right free wall flutter is often associated with persistent LRA
      conduction and additional radiofrequency ablation (RFA) in SR is usually
      required. Low RA pacing may be used to assess LRA conduction block and offers a
      robust endpoint for atypical RA free wall flutter ablation, which results in a
      high long-term cure rate.

PMID- 20039994
TI  - Correlates of insight among youth with obsessive-compulsive disorder.
AB  - BACKGROUND: Individuals with Obsessive-Compulsive Disorder (OCD) may lack insight
      into the irrational nature of their symptoms. Among adults with OCD, poor insight
      has been linked to greater symptom severity, increased likelihood of comorbid
      symptoms, lower adaptive functioning, and worse treatment outcomes. Parallel work
      regarding insight among children and adolescents, with OCD, is lacking. The aim
      of this research was to examine links between insight and demographic, cognitive,
      and clinical factors among youth with OCD. METHODS: Seventy-one youths with OCD
      (mean age = 11.7; 63% = male) were assessed as part of a larger treatment trial.
      Insight was measured via clinician interview. RESULTS: Youth with low insight had
      poorer intellectual functioning and reported decreased perception of control over
      their environment. Additionally, youth with low insight were more likely to be
      younger, to report higher levels of depressive symptoms, and to report lower
      levels of adaptive functioning. CONCLUSION: This set of cognitive, developmental
      and clinical factors that may predispose youth with OCD to have diminished
      insight. Data provide initial empirical support for diagnostic differences
      between youth and adults with regard to requiring intact insight. Implications
      for treatment are discussed.

PMID- 20039995
TI  - The role of callous and unemotional traits in the diagnosis of conduct disorder.
AB  - BACKGROUND: Callous and unemotional (CU) traits might usefully subtype DSM-IV
      conduct disorder (CD). We investigate this hypothesis in a large, nationally
      representative sample of 5-16-year-olds. We also examine the characteristics of
      children with high CU traits but without CD. METHODS: Data come from the 2004
      British Child and Adolescent Mental Health Survey including 7,977 children, 5,326
      of whom were followed up after 3 years. DSM-IV diagnoses of psychiatric disorder
      were based on parent, teacher and child report. CU traits were assessed by parent
      report. RESULTS: Of the 2% of the sample who were diagnosed with DSM-IV CD, 46.1%
      were high on CU traits. In addition, 2.9% of the sample were high on CU traits
      without CD. Children with CD and CU traits showed more severe behavioural
      disturbance and were at substantially higher risk of CD diagnosis 3 years later.
      Children high on CU traits without CD showed evidence of disturbed functioning.
      CONCLUSIONS: Subtyping CD using CU traits identifies children with more severe
      and persistent psychopathology. Children with high CU traits but no CD diagnosis
      require further investigation.

PMID- 20039996
TI  - Evaluation of documented nursing care plans by the use of nursing-sensitive
      outcome indicators.
AB  - RATIONALE AND AIM: There is a lack of evidence that nursing care plans affect
      patient outcomes. The aim of the present study was to evaluate whether documented
      nursing care plans affect patient outcomes by the use of nursing-sensitive
      outcome indicators. METHOD: A retrospective, cross-sectional design with patients
      surveyed at time of discharge from two hospital units for patients with stroke
      and after 2-3 weeks at home. The control unit (A) did not employ care plans. The
      intervention unit (B) used care plans on a daily basis. Outcome was measured by
      'the National Stroke Register' and the two questionnaires: 'Quality of patients'
      perspective' and 'Euroquol five dimensions'. Data were collected over a 5-month
      period (October 2007-February 2008). RESULTS: In total, 87 patients were included
      in the study. Patient characteristics in the two groups at admission and the
      health-related quality of life 2 to 3 weeks after discharge were similar. The
      patients from unit B were more satisfied with individual care (P = 0.03) and
      participation (P = 0.007). Unit B also had a shorter length of stay (P = 0.004).
      CONCLUSIONS: The effects of documented care plans are difficult to evaluate from
      a patient perspective, as many factors can improve the outcome. However,
      documentation of care plans is a prerequisite for measuring the quality and
      outcome of the care provided. This small study indicates that documented care
      plans may affect patient satisfaction regarding individual care, participation
      and length of hospital stay.

PMID- 20039997
TI  - Exercise parameters in the treatment of clinical depression: a systematic review
      of randomized controlled trials.
AB  - RATIONALE, AIMS AND OBJECTIVES: Previous systematic reviews have concluded that
      exercise programmes are effective in the management of clinical depression. The
      aim of this review was to analyse the parameters of exercise programmes reported
      in the primary research, in order to provide clinicians with evidence-based
      recommendations for exercise prescription for clinical depression. METHODS: A
      systematic review of randomized controlled trials was undertaken. Only trials
      that reported exercise to be effective in treating depression were included and
      our review was limited to adults. Appropriate databases and reference lists were
      searched using established keywords. Data relating to the type, intensity,
      frequency, duration, mode of exercise and mode of application of exercise was
      extracted and collated. RESULTS: A total of 14 randomized controlled trials were
      included in this review and from these trials 20 intervention arms were analysed.
      The majority of trials used an aerobic exercise intervention and were supervised.
      The most common exercise parameters were 60-80% of maximum heart rate for 30
      minutes three times per week for an overall duration of 8 weeks. There is an
      equal volume of evidence supporting group as opposed to individually completed
      exercise programmes and no trends were identified which would support one mode of
      exercise over another. CONCLUSIONS: Currently the primary research on this topic
      supports the use of aerobic exercise which is supervised in some capacity. The
      current evidence base supports a prescription of three 30-minute sessions per
      week of aerobic exercise at 60-80% of maximum heart rate for at least 8 weeks.

PMID- 20039998
TI  - Nonlinear selection and the evolution of variances and covariances for continuous
      characters in an anole.
AB  - The pattern of genetic variances and covariances among characters, summarized in
      the additive genetic variance-covariance matrix, G, determines how a population
      will respond to linear natural selection. However, G itself also evolves in
      response to selection. In particular, we expect that, over time, G will evolve
      correspondence with the pattern of multivariate nonlinear natural selection. In
      this study, we substitute the phenotypic variance-covariance matrix (P) for G to
      determine if the pattern of multivariate nonlinear selection in a natural
      population of Anolis cristatellus, an arboreal lizard from Puerto Rico, has
      influenced the evolution of genetic variances and covariances in this species.
      Although results varied among our estimates of P and fitness, and among our
      analytic techniques, we find significant evidence for congruence between
      nonlinear selection and P, suggesting that natural selection may have influenced
      the evolution of genetic constraint in this species.

PMID- 20039999
TI  - Increased opportunity for sexual conflict promotes harmful males with elevated
      courtship frequencies.
AB  - Mating systems have a profound influence on the probability of conflict occurring
      between the sexes. Promiscuity is predicted to generate sexual conflict, thereby
      driving the evolution of male traits that harm females, whereas monogamy is
      expected to foster reproductive cooperation, thus rendering such traits
      redundant. We tested these predictions using experimentally evolved Drosophila
      pseudoobscura subject to different mating systems. Female survival was not
      influenced by the mating system treatment of her partner. However, females
      continuously housed with males evolving under elevated opportunities for female
      promiscuity produced fewer total progeny, but a relatively greater number of
      progeny early in their lives, than females housed with males evolving under
      obligate monogamy. We also found that promiscuous males courted females more
      frequently than monogamous males. Variation in male courtship frequency and
      progeny production patterns among treatments reinforces the critical importance
      of mating system variation for sexual conflict, during both pre- and post
      copulatory interactions.

PMID- 20040000
TI  - A microsatellite linkage map for Drosophila montana shows large variation in
      recombination rates, and a courtship song trait maps to an area of low
      recombination.
AB  - Current advances in genetic analysis are opening up our knowledge of the genetics
      of species differences, but challenges remain, particularly for out-bred natural
      populations. We constructed a microsatellite-based linkage map for two out-bred
      lines of Drosophila montana derived from divergent populations by taking
      advantage of the Drosophila virilis genome and available cytological maps of both
      species. Although the placement of markers was quite consistent with cytological
      predictions, the map indicated large heterogeneity in recombination rates along
      chromosomes. We also performed a quantitative trait locus (QTL) analysis on a
      courtship song character (carrier frequency), which differs between populations
      and is subject to strong sexual selection. Linkage mapping yielded two
      significant QTLs, which explained 3% and 14% of the variation in carrier
      frequency, respectively. Interestingly, as in other recent studies of traits
      which can influence speciation, the strongest QTL mapped to a genomic region
      partly covered by an inversion polymorphism.

PMID- 20040001
TI  - Mitochondrial haplotype does not affect sperm velocity in the zebra finch
      Taeniopygia guttata.
AB  - Mitochondrial DNA (mtDNA) variation has been suggested as a possible cause of
      variation in male fertility because sperm activity is tightly coupled to
      mitochondrial oxidative phosphorylation and ATP production, both of which are
      sensitive to mtDNA mutations. Since male-specific phenotypes such as sperm have
      no fitness consequences for mitochondria due to maternal mitochondrial (and
      mtDNA) inheritance, mtDNA mutations that are deleterious in males but which have
      negligible or no fitness effect in females can persist in populations. How often
      such mutations arise and persist is virtually unknown. To test whether there were
      associations between mtDNA variation and sperm performance, we haplotyped 250
      zebra finches Taeniopygia guttata from a large pedigreed-population and measured
      sperm velocity using computer-assisted sperm analysis. Using quantitative genetic
      'animal' models, we found no effect of mtDNA haplotype on sperm velocity.
      Therefore, there is no evidence that in this system mitochondrial mutations have
      asymmetric fitness effects on males and females, leading to genetic variation in
      male fertility that is blind to natural selection.

PMID- 20040002
TI  - Hidden cytoplasmic incompatibility alters the dynamics of male-killer/host
      interactions.
AB  - Wolbachia manipulate the reproduction of their arthropod hosts in a variety of
      ways. Recent work has demonstrated that these bacteria may combine phenotypes -
      possessing a 'male killing' phenotype and, where males survive, induce
      cytoplasmic incompatibility (CI). We here develop a mathematical model to
      investigate the extent to which 'hidden' CI may affect the evolutionary dynamics
      of host genes that suppress male-killing activity. We observed that for high
      prevalence infections, CI drives both suppressor and bacterium to higher
      frequency, such that the strain appears to solely exhibit CI. In contrast, for
      low prevalence infections, CI impedes suppressor invasion as surviving infected
      males are incompatible with the majority of females in the population. Our
      results demonstrate that 'hidden' phenotypes as well as observable ones can
      impact on the dynamics of the interaction, and knowledge of these is therefore
      required to predict when suppressor genes will invade, and the consequences of
      their invasion.

PMID- 20040003
TI  - A new stent design for the treatment of true bifurcation lesions: H-side branch
      stents.
AB  - BACKGROUND: There has been much debate for the adequate treatment strategies for
      true bifurcation lesions. The purpose of this study is to introduce and test a
      novel stent design for the treatment of true bifurcation lesions. METHODS: This
      side branch stent is composed of three parts: proximal, connecting, and distal
      parts. The distal part for the side branch vessel has a slope-side stent margin
      for circumferential coverage of the ostium and one radio-opaque marker for
      targeting the carina. The proximal part with two radio-opaque markers operates
      for safe stent delivery and useful guidance for a more precise placement of the
      distal part on the side branch ostium. Results of the in vitro test in the
      acrylic resin-made bifurcation phantom model were evaluated with microcomputer
      tomography. Animal experiments with this new stent platform were also performed
      in five pigs. RESULTS: In vitro test and microcomputer tomography showed complete
      coverage of the side branch ostium circumferentially with stent struts, and the
      absence of stent struts in the main vessel above the side branch ostium level.
      This side branch stents were successfully deployed in all 5 pigs. The results of
      animal experiments were also similar to those of in vitro tests. CONCLUSIONS: In
      vivo and vitro tests demonstrated the effective modality of this side branch
      stent for the treatment of true bifurcation lesions.

PMID- 20040004
TI  - Hemodynamic support using the Impella 2.5 catheter system during high-risk
      percutaneous coronary intervention in a patient with severe aortic stenosis.
AB  - The Impella 2.5 catheter is a percutaneously implanted left ventricular assist
      device cleared by the Food and Drug Administration to provide circulatory support
      for up to 6 hours. The presence of aortic stenosis is deemed to be a
      contraindication to its use, and ongoing clinical trials exclude patients with an
      aortic valve area of 1.5 cm(2) or less. We describe a case of severe aortic
      stenosis with an estimated valve area of 0.9 cm(2) and severe ischemic
      cardiomyopathy in whom the Impella catheter was successfully used for high-risk
      multivessel percutaneous coronary intervention.

PMID- 20040005
TI  - Pharmacokinetic sub-study in the SPIRIT III Randomized and Controlled Trial of
      XIENCE V everolimus eluting coronary stent system.
AB  - BACKGROUND: Drug-eluting stents (DES) are widely used for treatment of coronary
      artery disease with benefit of reduced restenosis compared to bare metal stents.
      The XIENCE VEverolimus Eluting Coronary Stent System is a second-generation DES
      system for better deliverability while maintaining safety and efficacy profiles.
      The present pharmacokinetic sub-study from the SPIRIT III Randomized and
      Controlled Trial (RCT) was to evaluate systemic exposure of patients to
      everolimus and to further demonstrate safety following implantation of XIENCE
      Vstents with everolimus doses ranging from 53 to 181 microg. METHODS AND RESULTS:
      Drug concentrations in whole blood were determined at multiple time points using
      a validated analytical method with a limit of quantification of 0.1 ng/mL.
      Individual C(max) ranged from 0.17 to 2.40 ng/mL and occurred between 0.07 and
      1.88 hours across all dose levels. Both mean and individual C(max) values were
      below the trough blood concentrations of everolimus (Certican) for inhibition of
      organ transplant rejection. The last time point at which drug concentrations
      could be quantified ranged from 12 to 168 hours postimplantation in individual
      patients. In most cases, the blood levels dropped below the limit of
      quantification after 72 hours. CONCLUSIONS: This study confirms that the XIENCE
      Vstent causes a limited and systemic exposure to everolimus. The presumed
      localized and efficient delivery of everolimus to target vessels coupled with
      limited and transient systemic drug exposure contributes to the safety and
      effectiveness of the XIENCE VEECSS in patients of SPIRIT III RCT for longer than
      2 years.

PMID- 20040006
TI  - Radial artery access as an emerging factor for decreasing mortality in
      cardiovascular interventions.
AB  - Transradial access for coronary interventions provides increased patient comfort,
      fewer access site complications, and reduced hospital stay and costs. However,
      the potential benefits favoring transradial access may be even more than these
      apparent advantages. Major bleeding after coronary interventions is an important
      factor contributing to mortality rates and can be dramatically reduced with the
      selection of the radial artery as the access site. Recent evidence suggests that
      the decrease in bleeding complications with transradial access may translate into
      a short- and long-term decrease in mortality in patients undergoing elective or
      urgent coronary interventions. In the era of complex coronary interventions with
      use of multiple antiplatelet and antithrombotic treatment regimens, the simple
      choice of transradial access for increasing patient comfort and decreasing
      bleeding complications and mortality is promising.

PMID- 20040007
TI  - Thrombocytopenia following percutaneous coronary intervention.
AB  - BACKGROUND: Thrombocytopenia following percutaneous coronary intervention (PCI)
      is an underappreciated condition that is often clinically challenging. There are
      no guidelines on the management of patients with this condition. OBJECTIVE: To
      review recent data in etiologies, risk factors, prevention, management, and
      prognostic implications of thrombocytopenia following PCI. EVIDENCE ACQUISITION:
      Search of MEDLINE, EMBASE, the Cochrane Database, and Google Scholar using the
      term thrombocytopenia + PCI and other relevant keywords to identify systematic
      reviews, clinical trials, cohort studies, case series, and case reports. The
      review was limited to English-language articles published between January 1980
      and June 2009. Articles on patients with baseline thrombocytopenia prior to PCI
      were excluded. EVIDENCE SYNTHESIS: Thrombocytopenia is not infrequent following
      PCI. The typical patient with post-PCI thrombocytopenia is on multiple therapies
      that can potentially cause a decrease in the platelet count. Identification of
      the cause is critical because management of the condition varies significantly
      based on the etiology. The severity of the thrombocytopenia also determines the
      clinical management of the patient. Several observational studies have
      demonstrated the adverse prognostic impact of the complication on clinical
      outcomes and have identified risk factors. CONCLUSIONS: Judicious use of
      therapies that can cause thrombocytopenia, efficient detection of the cause of
      the decrease in platelet count, and appropriate management of the condition can
      potentially improve the quality of care and outcomes following PCI. Further
      research into risk factors that predispose post-PCI patients to developing
      thrombocytopenia is warranted.

PMID- 20040008
TI  - Adverse events even after percutaneous coronary intervention: is there any way to
      predict it?
AB  - Since its development, the frequency and indication of percutaneous coronary
      intervention (PCI) have been increasing tremendously. Although generally the
      procedure shows promising results, some patients still develop cardiovascular
      events even after PCI. Some risk prediction models have been developed in order
      to identify this group of patients who possess higher risk of developing
      cardiovascular events after PCI. This article discusses the available risk
      prediction models, the difference between risk prediction models, choosing risk
      prediction models, and also limitations of the available risk prediction models.

PMID- 20040009
TI  - Idiopathic carotid and coronary vasospasm: a new syndrome?
AB  - We present the first case of cerebral infarction due to idiopathic reversible
      vasospasm of the extracranial internal carotid artery without headache or
      identifiable cause in a patient who subsequently suffered acute myocardial
      infarction due to vasospasm of the coronary artery.

PMID- 20040010
TI  - Thrombolysis in anterior versus posterior circulation strokes: timing of
      recanalization, ischemic tolerance, and other differences.
AB  - Previous studies have suggested a greater ischemic tolerance in posterior
      circulation as compared to anterior cerebral circulation. We aimed to investigate
      whether a differential response exists between anterior and posterior circulation
      strokes. Two hundred and four middle cerebral artery (MCA) patients and 28
      basilar artery occlusion (BAO) patients treated with intravenous recombinant
      tissue plasminogen activator were included. Transcranial Doppler assessed
      recanalization at different time points. Patients were divided in three groups:
      total time of ischemia (TTI)<6, 6-24, or>24 hours. We calculated the percentage
      of recovery (admission National Institutes of Health Stroke Scale [NIHSS]-
      discharge NIHSS/admission NIHSS)*100. Mean time to treatment was longer in BAO
      patients (P=.031). Early recanalization was more frequent among MCA occlusions
      (41% vs 29%; P=.039); the rate of persisting occlusion at 24 hours was similar
      (P=.933). Clinical recovery according to TTI was similar in each group: <6 hours:
      BAO 84%/MCA 69%; 6-24 hours: BAO 63%/MCA 61%; >24 hours: BAO -44%/MCA 11%
      (P=.23). For each hour of ischemia MCA patients worsened 1.78% (P=.035) and BAO
      1.76% (P=.421). MCA occlusions compared to BAO were independently associated with
      hemorrhagic transformation (OR: 8.2; P=.043). Our data do not support the theory
      of increased ischemic tolerance in posterior circulation. Despite longer time-to
      treatment, BAO were more resistant to hemorrhagic transformations.

PMID- 20040011
TI  - Diffusion tensor imaging of Guillain-Mollaret triangle in patients with
      hypertrophic olivary degeneration.
AB  - The aim of the study is to analyze diffusion tensor imaging (DTI) characteristics
      of the Guillain-Mollaret triangle (GMT) in patients with hypertrophic olivary
      degeneration (HOD) and to investigate their correlation with previously reported
      histopathology. DTI was performed in 10 patients diagnosed with HOD. Fractional
      anisotropy, apparent diffusion coefficient, axial diffusivity, and radial
      diffusivity were measured in the inferior olivary nucleus (IO), the central
      tegmental tract, the red and the dentate nuclei, and the superior cerebellar
      peduncle of HOD patients and compared to age, sex, and side-matched 10
      neurologically normal population. The prominent finding on DTI in affected IO was
      an increase in radial diffusivity compatible with demyelination. While
      conventional magnetic resonance imaging did not show any sign of involvement in
      the other components of GMT, DTI demonstrated signal changes in all anatomical
      components of the GMT. Main DTI findings in GMT of patients with HOD were an
      increase in radial diffusivity representing demyelination and an increase in
      axial diffusivity that is reflective of neuronal hypertrophy. DTI parameters can
      reflect the spatiotemporal evolution of transneuronal degeneration associated
      with HOD in a manner consistent with the known pathologic stages of HOD.

PMID- 20040012
TI  - A case of cervical spinal cord glioblastoma diagnosed with MR diffusion tensor
      and perfusion imaging.
AB  - Intramedullary glioblastomas in adult patients have rarely been reported. We
      describe magnetic resonance (MR) imaging findings, include findings on diffusion
      tensor imaging (DTI) and dynamic susceptibility contrast perfusion weighted
      imaging (PWI) in a case of autopsy-confirmed glioblastoma in a 72-year-old man.
      Serial MR examinations, DTI and PWI, and positron emission tomography
      examinations were performed. The tumor involved the medulla oblongata and the
      upper cervical spinal cord. Traditional MR imaging findings were unclear with
      regard to the differential diagnosis between intramedullary glioma or a
      tumefactive demyelinating lesion, but an increase in regional cerebral blood
      volume and a decrease in fractional anisotropy of the lesion correctly suggested
      a high-grade glioma. MR PWI and DTI may prove helpful to diagnose glioblastoma of
      the cervical cord when other imaging features are inconclusive.

PMID- 20040013
TI  - Internal border zone lesions as a predictor of early neurological deterioration
      in minor stroke patients with severe arterial steno-occlusion.
AB  - BACKGROUND: Early neurological deterioration (END) of acute ischemic stroke may
      be important because it can predict clinical outcomes. We described several cases
      with similar clinical findings but different outcomes and analyzed the
      characteristics of their imaging studies. We retrospectively analyzed minor
      stroke patients with severe arterial stenosis within 6 hours of stroke onset. We
      defined END as 4 or more deterioration of the National Institutes of Health
      Stroke Scale score. Diffusion-weighted imaging (DWI) lesions were classified as
      lesions of the pial artery (PI), perforating artery (PAI) and border-zone (BZ).
      RESULTS: We consecutively analyzed a total of 12 subjects in this study. The
      patterns of initial DWI lesions were internal BZ (50%), PI (50%), PAI (25%), and
      cortical BZ (16.7%). Among them, the number of subjects with END was 5, and the
      frequency of internal BZ on initial DWI was significantly higher in patients with
      END than in those without. CONCLUSIONS: In conclusion, the results of this study
      suggest that when internal BZ infarcts are detected in patients with acute minor
      strokes accompanied by severe arterial stenosis, close observation and careful
      management should be performed because END can be induced at an early stage.

PMID- 20040014
TI  - Successful recanalization of a septic embolus with a balloon mounted stent after
      failed mechanical thrombectomy.
AB  - Cardiac emboli are a feared complication for patients with left ventricular
      assist devices (LVAD). Septic emboli are rare but carry a poor prognosis in the
      setting of large artery occlusion. We report the case of a 24-year-old woman who
      presents with a left internal carotid artery terminus occlusion secondary to a
      septic emboli from a LVAD. The patient was not a candidate for intravenous
      thrombolytics due to an elevated international normalized ratio, and thus was
      taken for intra-arterial treatment. Initial treatment with mechanical
      thrombectomy and balloon angioplasty was not successful; thus, a balloon-mounted
      coronary stent was placed to achieve successful recanalization. Fragments of
      thrombus on the mechanical thrombectomy device revealed gram-positive bacilli on
      gram stain. Patients with large artery occlusion due to a septic embolus can be
      successfully treated with endovascular therapies in select patients.

PMID- 20040015
TI  - Universal screening for hyperbilirubinemia.

PMID- 20040016
TI  - HPV vaccination for the prevention of cervical cancer.

PMID- 20040017
TI  - Confidentiality in adolescent health care.

PMID- 20040018
TI  - Clinical significance of TC21 overexpression in oral cancer.
AB  - BACKGROUND: In search of novel molecular markers for oral cancer, we reported
      increased levels of TC21/R-Ras2 transcripts in oral squamous cell carcinoma by
      differential display. The aim of this study was to determine the clinical
      significance of TC21 in oral cancer. METHODS: Immunohistochemical analysis of
      TC21 protein expression was carried out in 120 leukoplakias, 83 OSCCs and 30 non
      malignant tissues, confirmed by immunoblotting, and correlated with
      clinicopathological parameters as well as disease prognosis. Co
      immunoprecipitation assays were carried out to identify the interaction partners
      of TC21 protein in oral cancer cells and tissues. RESULTS: TC21 nuclear
      expression increased from normal oral tissues to leukoplakia and frank malignancy
      (P < 0.001). TC21 overexpression was observed in 74.2% leukoplakia with no
      dysplasia, 75.9% dysplasias and 79.5% OSCCs in comparison with normal oral
      tissues. Receiver operating characteristic analysis showed that the area-under
      the curve values were 0.895, 0.885, and 0.919, while the positive predictive
      values were 95.8%, 95.6%, and 97.1%, for nuclear immunostaining for normal versus
      leukoplakia with no dysplasia, leukoplakic lesions with dysplasia, and OSCCs,
      respectively. Immunoblotting confirmed overexpression of TC21 in oral lesions.
      Using co-immunoprecipitation assays, we showed interactions of TC21 with Erk2,
      PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells. CONCLUSION: Our
      findings suggested that alteration in TC21 expression is an early event in oral
      cancer and correlates with poor prognosis of OSCCs. TC21 interactions with Erk2,
      PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells and tissues
      suggests the involvement of TC21 in signaling pathways in oral cancer.

PMID- 20040019
TI  - Oral cancer over four decades: epidemiology, trends, histology, and survival by
      anatomical sites.
AB  - BACKGROUND: Oral cancer is one of the few life-threatening oral diseases. The
      subtypes and different sites of oral cancer has different etiology epidemiology
      and survival rate. Prevalence of the various anatomical oral sites provided
      potential baseline for improvement of clinical approach. METHODS: Incidence and
      survival rates were derived from the Israel National Cancer Registry and included
      all registered data between 1970 and 2006. Oral cancer included the lips, tongue,
      buccal mucosa, gums, vestibulum, floor of the mouth, and palate. RESULTS: Most
      prevalent oral cancer subtype was squamous cell carcinoma (SCC) among men above
      the age of 55 years. Females had a higher incidence of SCC in lateral border of
      tongue, gums and buccal mucosa. Lymphoma and sarcoma were the most prevalent
      under the age of 20. Melanomas and metastatic disease revealed the lowest
      survival rate, while invasive or infiltrating basal cell carcinoma in the lips
      had the highest rate. The highest oral survival rate was for the lip, and the
      lowest was for the tongue and gums. CONCLUSIONS: Early detection of oral cancer
      is important for all the medical health team. Decrease in lip carcinoma may be a
      result of occupational or awareness changes and should be studied. Non-epithelial
      tumors under the age of 20 should be considered as a differential diagnosis. A
      basic oral examination should be included in all routine medical examinations,
      with emphasis on high-risk patients and high-risk oral sites.

PMID- 20040020
TI  - Detection of Notch signaling molecules in cemento-ossifying fibroma of the jaws.
AB  - BACKGROUND: The aim of this study was to evaluate the roles of Notch signaling in
      the oncogenesis and cytodifferentiation of cemento-ossifying fibroma, the
      expressions of Notch receptors and ligands were detected in COF and normal jaw
      bones. MATERIALS AND METHODS: The expressions of Notch1, Notch3, Jagged1, and
      Jagged2 were detected by reverse transcriptase polymerase chain reaction and
      immunohistochemistry respectively in 16 cases of normal bone tissues and 12 cases
      of COF of the jaws. RESULTS: The mRNAs expressions of Notch1, Notch3, Jagged1,
      and Jagged2 were detected in all specimens. The expression levels of mRNAs in COF
      were higher than those in normal bones. In COF, Notch proteins staining were
      showed extensively distribution in fibroblasts and osteoblasts. In normal bone
      tissue, Notch proteins were expressed in osteoblasts, whereas proteins staining
      were weaker than those in COF, but no detection in fibroblast-like bone marrow
      stroma cells. The expressions of Notch receptors and ligands were not detected in
      cementum-like products or bone matrices. CONCLUSION: Our data suggest that Notch
      signaling may participate in controlling cell differentiation and proliferation
      in normal bone and COF of the jaws. Notch signaling disorder may be a molecular
      incident in COF occurrence and development.

PMID- 20040022
TI  - Expression of mitotic checkpoint proteins BUB1B and MAD2L1 in salivary duct
      carcinomas.
AB  - OBJECTIVE: Defects in the mitotic checkpoint lead to aneuploidy and might
      facilitate tumorigenesis. However, the ploidy status in salivary duct carcinoma
      (SDC) has been reported to play limited role in prediction of prognosis. Thus, we
      need more reliable markers to reflect the rapid tumor progression in SDCs. We
      aimed here to investigate the expression of mitotic checkpoint proteins
      benzimidazole 1 homolog beta (BUB1B) and mitosis arrest-deficient 2 like 1
      (MAD2L1) in SDCs and to determine their possible role as surrogate prognostic
      markers. METHODS: We analyzed the clinical courses, pathologic findings and
      immunohistochemical profiles of mitotic checkpoint proteins (BUB1B and MAD2L1) in
      27 pathologically confirmed SDCs. The expression status of BUB1B and MAD2L1 was
      compared with clinicopathologic factors and other molecular markers, such as TGF
      beta, c-erb-B2, androgen receptor, vascular endothelial growth factor, and
      epidermal growth factor receptor, for prognostic significance. RESULTS: High
      BUB1B expression was detected in 25.9% of subjects, and high MAD2L1 expression
      was in 55.6% of subjects. However, survival analysis revealed that mitotic
      checkpoint expression did not have prognostic significance in SDCs, nor did the
      other studied markers. Rather, the clinical variable of N classification at
      diagnosis (in N+ status, hazard ratio 5.19, 95% CI 1.26-21.32 for disease-free
      survival and hazard ratio 7.18, 95% CI 1.09-46.99 for overall survival) was
      strongly associated with survival and prognosis based on the Cox proportional
      hazard model. CONCLUSIONS: Mitotic checkpoint proteins appeared to play a limited
      role in predicting prognosis in SDCs. Further study is required to elucidate the
      exact role of mitotic checkpoint proteins in SDCs.

PMID- 20040021
TI  - Fatty-acid-binding protein 5 promotes cell proliferation and invasion in oral
      squamous cell carcinoma.
AB  - BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most malignant
      neoplasms worldwide, and the molecular mechanism of oral tumorigenesis is still
      unclear. Fatty-acid-binding protein 5 (FABP5) was found in our previous study to
      be upregulated in oral squamous cell carcinomas by proteomic analysis. The
      implications of FABP5 overexpression in oral cancer progression have not yet been
      elucidated. MATERIALS AND METHODS: In this study, the recombinant adeno
      associated virus vectors were used to deliver and increase the expression of
      FABP5 in human OSCC cell lines. U6 promoter-driven short-hairpin RNA (shRNA)
      triggered RNA interference was used to block FABP5 gene expression. Transwell
      Matrigel invasion assay, MTS cell proliferation assay, reverse transcription
      polymerase chain reaction, Western blot, and gelatin zymography analysis were
      used to investigate the effects of FABP5 on cell invasion, growth, and matrix
      metalloproteinase (MMP) production. RESULTS: Overexpression of FABP5 in oral
      cancer cells increased cell proliferation and invasiveness by increasing the
      expression of MMP-9. Silencing FABP5 with shRNA significantly suppressed cell
      proliferation, MMP-9 activities, and invasiveness. CONCLUSION: Our study provides
      the first evidence that FABP5 expression modulated MMP-9 production and the
      invasive behavior of oral cancer cells and suggests that FABP5 may provide novel
      targets for therapeutic intervention.

PMID- 20040023
TI  - Oral Candida colonization and its relation with predisposing factors in HIV
      infected children and their uninfected siblings in Brazil: the era of highly
      active antiretroviral therapy.
AB  - OBJECTIVES: To evaluate predisposing factors such as orofacial manifestations,
      immunosuppression status and antiretroviral therapy in relation to oral
      colonization by Candida spp. in Brazilian HIV-infected children and their
      uninfected siblings in the era of highly active antiretroviral therapy (HAART).
      METHODS: Whole stimulated saliva was collected from 65 HIV-infected children
      (HIV+) and 40 uninfected siblings (HIV-), followed by assessment of orofacial
      manifestation, caries indexes and the number of cavitated dentinal carious teeth
      (CDT). The salivary samples were cultured and the colonies were counted. After
      which they were identified by sugar assimilation and fermentation (API 20C). Data
      was analyzed using chi-square, Mann-Whitney, Spearman tests and logistic
      regression. RESULTS: Regarding positive growth, HIV+ presented 80% (52/65) and
      HIV- 57.5% (23/40) (P = 0.013). Absence of antiretroviral therapy and HAART
      increased the probability of Candida isolation (P < 0.05). Mean CD4%, immune
      status and history of recurrent oral candidiasis (OC) had no influence on Candida
      isolation. Mixed Candida spp. cultures were observed in HIV+ (40%) and HIV-
      (52%): C. albicans was more frequently found in both groups, with a higher
      prevalence in HIV+ (P = 0.05); other non-albicans species were isolated in HIV+
      and HIV-. Low prevalence of orofacial manifestations was observed in HIV+ (10.7%
      of OC). There was an association between means of CDT and Candida growth (P <
      0.05) and a positive correlation between number of CDT and Candida cfu-counts in
      HIV+ and HIV-. Mean CD4% and immune-status had no influence on Candida isolation.
      Absence of antiretroviral therapy and HAART increased the probability of Candida
      isolation (P < 0.05). CONCLUSIONS: The HIV infected children had a significantly
      higher prevalence of oral Candida spp. compared to their uninfected siblings.
      Absence of HAART and presence of dentinal carious teeth increased significantly
      Candida spp. colonization in these children.

PMID- 20040024
TI  - DNA amplification and expression of FADD in oral squamous cell carcinoma.
AB  - BACKGROUND: The Fas-associated death domain-containing protein, FADD, is an
      adaptor for relaying apoptotic signals. However, recent studies have shown that
      FADD also plays an important role in the growth and regulation of the cell cycle.
      The purpose of this study was to elucidate the role of FADD in oral squamous cell
      carcinoma (SCC). METHODS: The DNA amplification of FADD from 30 samples of tongue
      SCC was analyzed using real-time PCR and the protein expression of FADD from 60
      samples of tongue SCC was analyzed using immunohistochemistry. RESULTS: The DNA
      amplifications of FADD were observed in 13 cases (44.3%) and were significantly
      correlated with the histopathological differentiation grade of SCCs (P = 0.009).
      FADD expression levels compared with the matched adjacent epithelium increased
      significantly (P = 0.000). Additionally, the positive expressions of FADD were
      significantly correlated with lymph node metastasis of SCCs (P = 0.029) and the 5
      year disease-specific survival rates (P = 0.049). A positive association between
      FADD expression level and the histopathological differentiation grade was found
      to be limited to T1 SCCs (P = 0.019). DNA amplification was moderately correlated
      (correlation coefficient = 0.406, P = 0.026) with expression of FADD in 30
      samples of tongue SCC. CONCLUSION: In tongue SCCs, the expression of FADD was
      higher when compared with that of adjacent areas, which might be determined via
      genomic amplification in 11q13.3. Thus, SCC cells with the expression of FADD are
      possibly more likely to become metastatic and to worsen survival rates.

PMID- 20040026
TI  - Relationship between pterygomaxillary notches and maxillary anterior teeth.
AB  - PURPOSE: Selection of the appropriate size of maxillary anterior teeth in
      complete dentures may be difficult, as there is no universally accepted method
      that can be used reliably. The aim of this study was to investigate whether there
      is a relationship between the total mesiodistal width of the six maxillary
      anterior teeth and the interpterygomaxillary notch distance. MATERIAL AND
      METHODS: One hundred and ten maxillary impressions were made on dental students
      (67 women, 43 men; 19 to 22 years old) using stock tray and irreversible
      hydrocolloid impression material. The mesiodistal width of the six maxillary
      anterior teeth and the distance of the interpterygomaxillary notch were measured
      by digital caliper on stone casts (on two separate occasions by two independent
      observers). The results were analyzed using correlation regression tests.
      RESULTS: The mean mesiodistal width of the six maxillary anterior teeth was 46.02
      (+/-2.8) mm, and the mean distance of the interpterygomaxillary notch was 42.38
      (+/-3.47) mm. A significant correlation was found between mesiodistal width of
      the maxillary anterior teeth and the interpterygomaxillary notch distance (p=
      0.003; r = 0.28). Standardized coefficient was found to be low (28%) to predict
      the appropriate size of maxillary anterior teeth. CONCLUSION: Total mesiodistal
      width of the maxillary anterior teeth correlated with the distance between
      pterygomaxillary notches; however, measurement of the interpterygomaxillary notch
      could not be used for tooth selection reliably due to the low standardized
      coefficient. Within the limitations of this study, the interpterygomaxillary
      notch distance is not useful for the selection of six maxillary anterior teeth in
      edentulous patients.

PMID- 20040025
TI  - Implant-supported obturator overdenture for extensive maxillary resection
      patient: a clinical report.
AB  - This clinical report presents an implant-retained obturator overdenture solution
      for a Prosthodontic Diagnostic Index Class IV maxillectomy patient with a large
      oronasal communication and severe facial asymmetry, loss of upper lip and
      midfacial support, severe impairment of mastication, deglutition, phonetics, and
      speech intelligibility. Due to insufficient bone support to provide satisfactory
      zygomaticus implant anchorage, conventional implants were placed in the body of
      the left zygomatic arch and in the right maxillary tuberosity. Using a modified
      impression technique, a cobalt-chromium alloy framework with three overdenture
      attachments was constructed to retain a complete maxillary obturator. Patient
      reported functional and quality of life measure outcomes were dramatically
      improved after treatment and at the two-year follow-up.

PMID- 20040027
TI  - Orthodontics using an occlusal splint: a clinical report.
AB  - Careful management of the occlusion is necessary for successful prosthodontic
      treatment. A reorganized occlusal approach requires a more accurate registration
      of the desired jaw position, and where it is difficult to achieve this, an
      occlusal splint is indicated. This clinical report documents a 60-year-old man
      with a Prosthodontic Diagnostic Index Class IV dentition, who prior to a full
      mouth reconstruction, underwent occlusal splint therapy with a Michigan-type
      splint that incorporated z-springs to allow concurrent orthodontic tooth movement
      of two anterior teeth to positions that would allow favorable restorations by
      correcting occlusal and esthetic form.

PMID- 20040028
TI  - Human perception of dental porcelain translucency correlated to
      spectrophotometric measurements.
AB  - PURPOSE: This study evaluated the relationship between instrumental measurements
      and subjective visual assessment of differences in dental porcelain translucency.
      MATERIALS AND METHODS: Unshaded feldspathic porcelain was used with controlled
      amounts of tin oxide to create two groups of 12-mm diameter disks with
      incremental changes in opacity. Contrast ratio (CR = Yb/Yw) was determined with a
      spectrophotometer, and used as a measure of porcelain translucency (Group A =
      0.20 to 0.40; Group B = 0.6-0.8). Within each group, there were 14 specimens with
      11 CRs. Three observer groups (first year dental students, residents, faculty
      with >10 years of shade matching experience) were recruited to assess the
      translucency between porcelain disks under two lighting conditions (reflected
      light, transmitted light). Each subject's ability to distinguish between
      specimens of differing translucency was determined. Descriptive statistics and
      three-way ANOVA followed by a post-hoc Tukey-Kramer test were used to evaluate
      the translucency perception threshold (TPT) of subjects (alpha= 0.05). RESULTS:
      The overall mean TPT (DeltaC) was 0.07, while 50% of the subjects could perceive
      a 0.06 CR difference between porcelain specimens. Three-way ANOVA revealed a
      significant difference in translucency perception among the observer groups (p <
      0.0001), whereas the main effects for porcelain opacity (p= 0.3038) and lighting
      condition (p= 0.0645) were not significant, and no significant interactions were
      found. Post-hoc Tukey-Kramer test indicated that the mean TPT observed in the
      faculty group (DeltaC = 0.04) was significantly lower than those observed in
      student (DeltaC = 0.09) and resident groups (DeltaC = 0.08), while there was no
      significant difference between students and residents. CONCLUSIONS: The overall
      mean TPT of all subjects was 0.07, and 50% of the study population perceived a
      0.06 CR difference in translucency. Increased shade matching experience (> or =10
      years) significantly improved the ability to perceive differences in
      translucency; however, neither the viewing condition nor porcelain opacity
      affected the perceived translucency threshold.

PMID- 20040029
TI  - Alternative pretreatment modalities with a self-adhesive system to promote
      dentin/alloy shear bond strength.
AB  - PURPOSE: The aim of this study was to evaluate alternative pretreatment
      modalities to enhance the dentin/alloy shear bond strength using a self-etch
      adhesive system. MATERIAL AND METHODS: Ninety discs were fabricated and divided
      into three groups (n = 30). The discs of the first group were cast in gold
      palladium (Au-Pd); those of the second group were cast in palladium silver alloy
      (Pd-Ag); the discs of third group were cast in nickel chromium alloy (Ni-Cr).
      Each group was further divided into three subgroups (n = 10) according to the
      dentin pretreatment used to lute the discs. Subgroup U (no pre-treatment): Rely X
      Unicem resin cement. Subgroup GU: G-Bond then Rely X Unicem. Subgroup ZU: Zinc
      Zeolite pretreatment then Rely X Unicem. Shear bond strength was determined using
      a compressive mode of force applied at the dentin/alloy interface using a
      monobevelled chisel-shaped metallic rod. Data were collected and statistically
      analyzed to assess the effect of alloy type, pretreatment modality, and their
      interactions on the shear bond strength. Scanning electron microscopic
      examination (1000x) at the dentin/resin interface was performed. Two-way ANOVA
      was used in testing significance for the effect of pretreatment, alloy, and their
      interaction. Duncan's post hoc test was used for pairwise comparison between the
      means when the ANOVA test was significant. The significance level was set at p<
      or = 0.05. Statistical analysis was performed with SPSS 15.0. RESULTS: Regarding
      the pretreatment modality, the mean shear bond strength and 95% CI of subgroups
      ZU (18.00 MPa; 16.8 to 19.2) and GU (16.91 MPa; 15.4 to 18.4) were significantly
      higher than subgroup U (12.81 MPa; 11.4 to 14.2). Regarding the alloy type, the
      mean shear bond strength and 95% CI of Ni-Cr groups (18.39 MPa; 16.9 to 19.9)
      were significantly higher than Au-Pd (15.33 MPa; 13.8 to 16.8) and Pd-Ag (13.99
      MPa; 12.3 to 15.7). CONCLUSIONS: Pretreatment of dentin with G-Bond and Zinc
      Zeolite improved the dentin/alloy shear bond strength. Base metal alloys provided
      superior bond strength values with any adhesive modality compared to noble
      alloys. Treatment of the dentin surface prior to the application of a self
      adhesive system is of great importance to enhancement of the dentin/alloy bond
      strength.

PMID- 20040030
TI  - Bond strength, microhardness, and core/veneer interface quality of an all-ceramic
      system.
AB  - PURPOSE: This study was designed to evaluate three veneering materials for an all
      ceramic alumina system in terms of bond strength, microhardness, and core/veneer
      interface quality. MATERIALS AND METHODS: Fifteen In-Ceram cores were constructed
      for this study, forming three groups of five specimens each divided by the
      veneering ceramic disc fired on the occlusal surface of the alumina core: Vitadur
      N, Vitadur Alpha, or VM7. The specimens underwent shear bond and microhardness
      testing. Gross examination of debonded discs by SEM and EDAX analysis was
      conducted. Data for shear bond strength (SBS) and microhardness were presented as
      means and standard deviation (SD) values. One-way ANOVA and Duncan's post hoc
      test were used for pairwise comparison between the means when ANOVA test was
      significant. RESULTS: VM7 showed the highest shear bond value and lowest
      microhardness values of the three tested veneering materials. No statistically
      significant difference was evident between the SBSs of Vitadur N and Vitadur
      Alpha to the alumina cores. Vitadur Alpha showed statistically the highest mean
      VHN, followed by Vitadur N, while VM7 showed statistically the lowest mean values
      of VHN. CONCLUSIONS: In-Ceram core/Vitadur N disc debondings appeared to be
      interfacial by complete delaminations, leaving a shiny visible and quite distinct
      area, whereas there appeared to be perfect adhesion between the core and VM7
      veneering material. VM7 appeared to possess ultra-fine texture with intimate
      contact to the core, forming what seemed like a transition zone where the ceramic
      and core appeared to blend for a distance. VM7's finer particle size has improved
      the core/veneer bond strength and decreased micohardness values. This new
      veneering material will probably enhance the performance and esthetics of the In
      Ceram system.

PMID- 20040031
TI  - Conversion degree of indirect resin composites and effect of thermocycling on
      their physical properties.
AB  - PURPOSE: This study evaluated the degree of conversion (DC) of four indirect
      resin composites (IRCs) with various compositions processed in different
      polymerization units and investigated the effect of thermal aging on the flexural
      strength and Vicker's microhardness. MATERIALS AND METHODS: Specimens were
      prepared from four IRC materials, namely Gr 1: Resilab (Wilcos); Gr2: Sinfony (3M
      ESPE); Gr3: VITA VMLC (VITA Zahnfabrik); Gr4: VITA Zeta (VITA Zahnfabrik) using
      special molds for flexural strength test (N = 80, n = 10 per group) (25 x 2 x 2
      mm(3), ISO 4049), for Vicker's microhardness test (N = 80, n = 10 per group) (5 x
      4 mm(2)) and for DC (N = 10) using FT-Raman Spectroscopy. For both flexural
      strength and microhardness tests, half of the specimens were randomly stored in
      distilled water at 37 degrees C for 24 hours (Groups 1 to 4), and the other half
      (Groups 5 to 8) were subjected to thermocycling (5000 cycles, 5 to 55 +/- 1
      degree C, dwell time: 30 seconds). Flexural strength was measured in a universal
      testing machine (crosshead speed: 0.8 mm/min). Microhardness test was performed
      at 50 g. The data were analyzed using one-way and two-way ANOVA and Tukey's test
      (alpha= 0.05). The correlation between flexural strength and microhardness was
      evaluated with Pearson's correlation test (alpha= 0.05). RESULTS: A significant
      effect for the type of IRC and thermocycling was found (p= 0.001, p= 0.001) on
      the flexural strength results, but thermocycling did not significantly affect the
      microhardness results (p= 0.078). The interaction factors were significant for
      both flexural strength and microhardness parameters (p= 0.001 and 0.002,
      respectively). Thermocycling decreased the flexural strength of the three IRCs
      tested significantly (p < 0.05), except for VITA Zeta (106.3 +/- 9.1 to 97.2 +/-
      14 MPa) (p > 0.05) when compared with nonthermocycled groups. Microhardness
      results of only Sinfony were significantly affected by thermocycling (25.1 +/-
      2.1 to 31 +/- 3.3 Kg/mm(2)). DC values ranged between 63% and 81%, and were not
      significantly different between the IRCs (p > 0.05). While a positive correlation
      was found between flexural strength and microhardness without (r = 0.309) and
      with thermocycling (r = 0.100) for VITA VMLC, negative correlations were found
      for Resilab under the same conditions (r =-0.190 and -0.305, respectively)
      (Pearson's correlation coefficient). CONCLUSION: Although all four IRCs presented
      nonsignificant DC values, flexural strength and microhardness values varied
      between materials with and without thermocycling.

PMID- 20040032
TI  - The effect of denture cleansing solutions on the retention of pink Locator
      attachments: an in vitro study.
AB  - PURPOSE: To evaluate the changes in retention of pink Locator attachments after
      exposure to various denture cleansers. MATERIALS AND METHODS: Six groups (20
      pairs each) of pink Locator attachments (3.0 lb. Light Retention replacement
      patrix attachments) were soaked for the equivalent of 6 months of clinical use in
      the following solutions: Water (control), Polident Regular, Efferdent, 6.15%
      sodium hypochlorite (NaOCL, 1:10 dilution), Polident Overnight, and Cool Mint
      Listerine mouthwash. A universal testing machine set at a crosshead speed of 2
      in/min was used to perform one pull. The peak load-to-dislodgement was recorded
      to reflect changes in the retention of the Locator attachments after soaking.
      Data were analyzed by one-way ANOVA followed by Tukey's Honestly Significant
      Difference test. A p< or = 0.05 was considered significant. RESULTS: Denture
      cleansing solutions significantly affected the retentive values of pink Locator
      attachments (F = 344.3, p< or = 0.0001). Cool Mint Listerine mouthwash increased
      the retentive values of the attachments (51.10 +/- 5.31 N) when compared to the
      control group (45.25 +/- 3.49 N). There was no significant difference in the
      retentive values of attachments soaked in Polident Regular or Polident Overnight
      when compared to the control group. Efferdent caused a small reduction in the
      retentive values (40.81 +/- 2.56 N) and most importantly, diluted NaOCl caused a
      large reduction in the retentive values (7.83 +/- 2.50 N) of pink Locator
      attachments. In addition, Cool Mint Listerine mouthwash caused blue discoloration
      of the Locator attachments, and NaOCl caused whitening and softening of the pink
      Locator attachments. CONCLUSION: Cool Mint Listerine and Efferdent's small effect
      on the retentive values of the Locators might be clinically unimportant; however,
      NaOCl caused a large reduction in the retentive values of the attachments.
      Because of their effect on retentive values and on the color of the Locator
      attachments, NaOCl and Cool Mint Listerine are not recommended. These results
      should be interpreted clinically with caution, realizing that different results
      may be obtained when fatigue stress during function and multiple pulls (in vivo)
      are combined with the chemical action of denture cleansers.

PMID- 20040033
TI  - Predoctoral implant education: the Creighton experience at 20 years.
AB  - The landscape of predoctoral implant education has changed dramatically in the
      short span of two decades. Documented success and increased patient demands have
      driven heightened expectations upon the educational community. Predoctoral
      education must play a pivotal role in preparing the profession to meet these new
      opportunities. The evolution of implant education in the predoctoral sector is
      examined, and a typical implant program is described.

PMID- 20040034
TI  - Effect of surface conditioning and taper angle on the retention of IPS e.max
      Press crowns.
AB  - PURPOSE: The objective of this study was to evaluate the retentive strength of
      single-unit crowns with 10 degrees and 26 degrees taper angles cemented using two
      surface conditioning methods. MATERIALS AND METHODS: Thirty-two freshly extracted
      sound human molars were divided into two groups (n = 16) and prepared in a
      standardized manner with 10 degrees and 26 degrees taper angles. All-ceramic (IPS
      e.max Press) single crowns were fabricated for the prepared teeth. The crowns
      were then subdivided into two groups (n = 8), according to type of surface
      conditioning for the intaglio surfaces. Half the groups were HF acid etched and
      silanized, and the other half were conditioned with tribochemical silica coating
      and silanization. The crowns were cemented using adhesive cement (Panavia F 2.0).
      Retentive strength was measured in a universal testing machine. RESULTS: No
      significant difference was found between the mean retention forces for both 10
      degrees and 26 degrees taper angles when the crowns were conditioned either with
      silica coating (613 +/- 190 N and 525 +/- 90 N, respectively), or with
      hydrofluoric (HF) acid etching and silanization (550 +/- 110 N and 490 +/- 130 N
      for 10 degrees and 26 degrees, respectively) (p= 0.32). CONCLUSION: Neither the
      surface conditioning type, nor the taper angle affected the retentive strength of
      IPS e.max Press single-unit crowns when cemented adhesively. Since silica coating
      and silanization did not show significant differences from HF acid gel and
      silanization, the former can be preferred for conditioning intaglio surfaces of
      glass ceramic crowns to avoid the use of the hazardous compound HF acid gel
      chairside.

PMID- 20040035
TI  - Influence of surface treatment on the shear bond strength of ceramics fused to
      cobalt-chromium.
AB  - PURPOSE: To evaluate the influence of surface treatment on the shear bond
      strength between a Co-Cr alloy and two ceramics. MATERIALS AND METHODS: Forty
      eight metal cylinders were made (thickness: 4 mm, height: 3.7 mm) according ISO
      TR 11405. The 48 metallic cylinders were divided into four groups (n = 12),
      according to the veneering ceramic (StarLight Ceram and Duceram Kiss) and surface
      treatments: air-particle abrasion with Al(2)O(3) or tungsten drill (W). Gr1:
      StarLight + Al(2)O(3); Gr2: StarLight + W; Gr3: Duceram + Al(2)O(3); and Gr4:
      Duceram + W. The specimens were aged using thermal cycling (3000x, 5 to 55
      degrees C, dwell time: 30 seconds, transfer time: 2 seconds). The shear test was
      performed with a universal testing machine, using a load cell of 100 kg (speed:
      0.5 mm/min) and a specific device. The bond strength data were analyzed using
      ANOVA and Tukey's test (5%), and the failure modes were analyzed using an optical
      microscope (30x). RESULTS: The means and standard deviations of the shear bond
      strengths were (MPa): G1 (57.97 +/- 11.34); G2 (40.62 +/- 12.96); G3 (47.09 +/-
      13.19); and G4 (36.80 +/- 8.86). Ceramic (p= 0.03252) and surface treatment (p=
      0.0002) significantly affected the mean bond strength values. CONCLUSIONS: Air
      particle abrasion with Al(2)O(3) improved the shear bond strength between metal
      and ceramics used.

PMID- 20040036
TI  - Catastrophizing and symptoms of sleep disturbances in children.
AB  - Catastrophizing about sleeplessness is a cognitive process associated with sleep
      disturbance in adults. This study aimed to (1) examine whether children
      catastrophize about the consequences of not sleeping; (2) define the topics that
      children catastrophize about; (3) assess whether there is a link between
      catastrophizing and sleep disturbance in children; and (4) examine whether an
      association between catastrophizing and sleep in children is mediated by anxiety
      and depression symptoms. Children completed the sleep self-report and a
      catastrophizing interview. Testing took place in two inner-city schools in
      London, UK and participants comprised 123 children aged between 8 and 10 years
      (49% male). Thirty-four (28%) participants reported concerns in response to the
      catastrophizing questionnaire. The main topics being catastrophized were concerns
      about sleep, physiological issues and one's own emotions. Catastrophes predicted
      sleep disturbance after controlling for age and sex (beta = 0.35, P < 0.001) but
      not when controlling additionally for anxiety and depression symptoms (beta =
      0.15, P = 0.106). Symptoms of anxiety (Sobel test = 3.30, P < 0.001) and
      depression (Sobel test = 2.90, P = 0.004) mediated the influence of
      catastrophizing on sleep. A proportion of children catastrophized about the
      consequences of sleeplessness and this was associated with sleep disturbance, an
      association which was mediated through anxiety and depression symptoms.

PMID- 20040037
TI  - Effect of sleep deprivation on multi-unit discharge activity of basal forebrain.
AB  - The basal forebrain (BF) is an important wakefulness/arousal-promoting structure
      involved in homeostatic responses to sleep deprivation (SD). However, the effects
      of SD and subsequent sleep recovery on the BF discharge have not been
      investigated. Multi-unit BF activity was recorded on freely moving rats during 8
      h of baseline (BL) and, on the following day, during 4 h of SD by gentle handling
      followed by 4 h of recovery. The effect of SD on the waking discharge was
      evaluated during the last 10 min of each hour when attentive waking was induced.
      The wakefulness level was defined based on the ratio between theta and delta
      electroencephalogram (EEG) powers, and epochs with ratios >or=1 but <2 (T/D-1)
      and >or=2 but <4 (T/D-2) were analysed separately. During T/D-1 wakefulness, the
      BF multi-unit discharge rate increased significantly during the second and third
      hours of SD and decreased during the third hour of recovery when compared with
      corresponding hours of BL. Non-rapid eye movement sleep discharge rate during
      recovery decreased significantly in the second and third versus the first and
      last hours. The results suggest that maintenance of the level of vigilance
      necessary for adequate performance during SD requires increased activation of BF
      neurones when compared with the BL, whereas the same level of vigilance after
      several hours of recovery can be maintained with lesser activation of BF
      neurones.

PMID- 20040038
TI  - The activation of the inflammatory cytokines in overweight patients with mild
      obstructive sleep apnoea.
AB  - It is widely accepted that obstructive sleep apnoea (OSA) is linked with
      cardiovascular diseases. The relationship is complex and remains still poorly
      understood. The presence of chronic systemic inflammation has been connected with
      pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is
      believed to be a process of many years, little is known about the potential
      impact of the largest OSA subgroup, mild OSA, on the development of
      cardiovascular diseases. The aim of the present study was to assess whether
      untreated mild OSA is associated with an activation of inflammatory cytokine
      system. The adult study population consisted of two groups: 84 patients with mild
      OSA [apnoea-hypopnoea index (AHI) 5-15 h(-1)] and 40 controls (AHI <5 h(-1)).
      Serum concentrations of pro- and anti-inflammatory cytokines were measured before
      any interventions. After adjustments for age, sex, body mass index, fat
      percentage, most important cardiometabolic and inflammatory diseases, and non
      steroidal anti-inflammatory medication, the mean level of tumour necrosis factor
      alpha was significantly elevated (1.54 versus 1.17 pg mL(-1), P = 0.004), whereas
      the level of interleukin-1 beta (IL-1 beta) was reduced (0.19 versus 0.23 pg mL(
      1), P = 0.004) in patients with mild OSA compared with controls. The
      concentrations of the protective anti-inflammatory cytokines, interleukin-10
      (1.28 versus 0.70 pg mL(-1), P < 0.001) and interleukin-1 receptor antagonist
      (478 versus 330 pg mL(-1), P = 0.003) were elevated in the OSA group. The
      concentrations of C-reactive protein increased, but IL-1 beta decreased along
      with the increase of AHI. Mild OSA was found to be associated not only with the
      activation of the pro-inflammatory, but also with the anti-inflammatory systems.

PMID- 20040039
TI  - Vitamin K to reverse the anticoagulant effect of vitamin K antagonists: can you
      teach an old dog new tricks?

PMID- 20040040
TI  - Effect of an increased clopidogrel maintenance dose or lansoprazole co
      administration on the antiplatelet response to clopidogrel in CYP2C19-genotyped
      healthy subjects.

PMID- 20040041
TI  - Comparing consensus guidelines on thromboprophylaxis in orthopedic surgery.
AB  - BACKGROUND: Different guidelines exist regarding the prevention of venous
      thromboembolism (VTE) in orthopedic surgery. OBJECTIVES: We aimed to compare
      (inter)national guidelines and analyse differences. METHODS: MEDLINE, the
      Cochrane Library and the internet were searched for guidelines on the prevention
      of VTE in orthopedic surgery. From these, we constructed a table comparing the
      different antithrombotic regimens during different orthopedic surgical and
      plaster cast treatments. RESULTS: Eleven guidelines from nine different countries
      and one international guideline were included. Few guidelines advise on
      thrombosis prophylaxis after plaster cast immobilization, (prolonged)
      arthroscopic surgery and isolated lower extremity trauma. Different opinions
      exist on the sole use of aspirin and mechanical prophylaxis and on the use of
      vitamin K antagonists after major hip and knee surgery. CONCLUSION: Based on the
      same available literature, different guidelines recommend different
      thromboprophylactic regimens. Ideally, the grade of recommendation should be
      based on the same level of evidence world-wide. Whilst there is no agreement on
      the relevance of different endpoints (e.g. asymptomatic DVT), it is very
      difficult to reach a consensus. Thromboprophylaxis guidelines should be reviewed
      and updated on a regular basis, because the evidence is evolving rapidly.

PMID- 20040042
TI  - Which platelet function test is suitable to monitor clopidogrel responsiveness? A
      pharmacokinetic analysis on the active metabolite of clopidogrel.
AB  - BACKGROUND: Multiple platelet function tests claim to be P2Y12-pathway specific
      and capable of capturing the biological activity of clopidogrel. OBJECTIVES: The
      aim of the present study was to determine which platelet function test provides
      the best reflection of the in vivo plasma levels of the active metabolite of
      clopidogrel (AMC). PATIENTS/METHODS: Clopidogrel-naive patients scheduled for
      elective percutaneous coronary intervention (PCI) received a 600 mg loading dose
      of clopidogrel and 100 mg of aspirin. For pharmacokinetic analysis, blood was
      drawn at 0, 20, 40, 60, 90, 120, 180, 240 and 360 min after clopidogrel loading
      and peak plasma concentrations (C(max)) of the AMC were quantified with liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Platelet function testing was
      performed at baseline and 360 min after the clopidogrel loading. RESULTS: The
      VASP-assay, the VerifyNow P2Y12-assay and 20 micromol L(-1) adenosine diphosphate
      (ADP)-induced light transmittance aggregometry (LTA) showed strong correlations
      with C(max) of the AMC (VASP: R(2) = 0.56, P < 0.001; VerifyNow platelet
      reactivity units (PRU): R(2) = 0.48, P < 0.001; VerifyNow %inhibition: R(2) =
      0.59, P < 0.001; 20 micromol L(-1) ADP-induced LTA: R(2) = 0.47, P < 0.001).
      Agreement with C(max) of the AMC was less evident for 5 micromol L(-1) ADP
      induced LTA or whole blood aggregometry (WBA), whereas the IMPACT-R ADP test did
      not show any correlation with plasma levels of the AMC. CONCLUSION: The flow
      cytometric VASP-assay, the VerifyNow P2Y12 assay and, although to a lesser
      extent, 20 micromol L(-1) ADP-induced LTA correlate best with the maximal plasma
      level of the AMC, suggesting these may be the preferred platelet function tests
      for monitoring the responsiveness to clopidogrel.

PMID- 20040043
TI  - Non-genomic effects of PPARgamma ligands: inhibition of GPVI-stimulated platelet
      activation.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-(gamma) (PPAR(gamma)) is
      expressed in human platelets although in the absence of genomic regulation in
      these cells, its functions are unclear. OBJECTIVE: In the present study, we aimed
      to demonstrate the ability of PPAR(gamma) ligands to modulate collagen-stimulated
      platelet function and suppress activation of the glycoprotein VI (GPVI) signaling
      pathway. METHODS: Washed platelets were stimulated with PPAR(gamma) ligands in
      the presence and absence of PPAR(gamma) antagonist GW9662 and collagen-induced
      aggregation was measured using optical aggregometry. Calcium levels were measured
      by spectrofluorimetry in Fura-2AM-loaded platelets and tyrosine phosphorylation
      levels of receptor-proximal components of the GPVI signaling pathway were
      measured using immunoblot analysis. The role of PPAR(gamma) agonists in thrombus
      formation was assessed using an in vitro model of thrombus formation under
      arterial flow conditions. RESULTS: PPAR(gamma) ligands inhibited collagen
      stimulated platelet aggregation that was accompanied by a reduction in
      intracellular calcium mobilization and P-selectin exposure. PPAR(gamma) ligands
      inhibited thrombus formation under arterial flow conditions. The incorporation of
      GW9662 reversed the inhibitory actions of PPAR(gamma) agonists, implicating
      PPAR(gamma) in the effects observed. Furthermore, PPAR(gamma) ligands were found
      to inhibit tyrosine phosphorylation levels of multiple components of the GPVI
      signaling pathway. PPAR(gamma) was found to associate with Syk and LAT after
      platelet activation. This association was prevented by PPAR(gamma) agonists,
      indicating a potential mechanism for PPAR(gamma) function in collagen-stimulated
      platelet activation. CONCLUSIONS: PPAR(gamma) agonists inhibit the activation of
      collagen-stimulation of platelet function through modulation of early GPVI
      signalling.

PMID- 20040044
TI  - The incidence, risk factors and prognostic implications of venous thromboembolism
      in patients with gastric cancer.
AB  - BACKGROUND: Data on venous thromboembolism (VTE) in gastric cancer (GC) are very
      scarce. OBJECTIVE: To investigate the incidence, risk factors and prognostic
      implications of VTE in Asian GC patients. METHODS: Prospective databases
      containing clinical information on GC patients (n = 2,085) were used. RESULTS:
      The 2-year cumulative incidences of all VTE events were 0.5%, 3.5% and 24.4% in
      stages I, II-IV(M0) and IV(M1), respectively. Advanced stage, older age and no
      major surgery were independent risk factors for developing VTE. When the VTE
      cases were classified into extremity venous thrombosis (EVT), pulmonary
      thromboembolism (PTE) or intra-abdominal venous thrombosis (IVT), IVTs (62%) were
      more common than EVTs (21%) or PTEs (17%). Although peri-operative pharmacologic
      thromboprophylaxis was not routinely administered, the VTE incidence after major
      surgery was only 0.2%. During chemotherapy, EVT/PTE developed more frequently
      than IVT (54% vs. 19%); however, during untreated or treatment-refractory
      periods, IVT developed more frequently than EVT/PTE (69% vs. 36%). In
      multivariate models, the development of EVT/PTE was a significant predictor of
      early death when compared with no occurrence of VTE (P < 0.05). However, IVT did
      not affect survival. CONCLUSION: This is the largest study that specially focused
      on VTE in GC and the VTE incidence in Asian GC patients was first demonstrated.
      Considering the low incidence of post-operative VTE development, the necessity of
      peri-operative pharmacologic thromboprophylaxis should be evaluated separately in
      Asian patients. The clinical situation of the development of EVT/PTE and IVT
      differed. Only EVT/PTE had an adverse effect on survival and IVT had no
      prognostic significance.

PMID- 20040045
TI  - HCV drug discovery aimed at viral eradication.
AB  - Hepatitis C virus (HCV) causes significant morbidity and mortality worldwide with
      nearly 3% of the world population infected by this virus. Fortunately, this virus
      does not establish latency, and hence it may be possible to eradicate it. HCV is
      strongly associated with liver cirrhosis and hepatocellular carcinoma and is
      currently treated with pegylated interferon-alpha (peg-IFN-alpha) and ribavirin.
      Unfortunately, these limited treatment options often produce significant side
      effects, and currently, complete eradication of virus with combined drug
      modalities has not yet been achieved for the majority of chronically HCV-infected
      individuals. Restricted treatment options, lack of a universal cure for HCV and
      the link between chronic infection, liver cirrhosis and hepatocellular carcinoma
      necessitate design of novel drugs and treatment options. Understanding the
      relationship between the immune response, viral clearance and inhibition of viral
      replication with pharmacology-based design can ultimately allow for complete
      eradication of HCV. This review focuses upon significant novel preclinical and
      clinical specifically targeted antiviral therapy (STAT-C) drugs under
      development, highlights their mechanism of action, and discusses their impact on
      systemic viral loads and permanent clearance of infection.

PMID- 20040046
TI  - Recent advances in Hepatitis E virus.
AB  - Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the
      family Hepeviridae. At least four major genotypes of HEV have been recognized:
      genotypes 1 and 2 are restricted to humans and associated with epidemics in
      developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans
      and several other animals in both developing and industrialized countries.
      Besides humans, strains of HEV have been genetically identified from swine,
      chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three
      open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for
      capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and
      ORF3 proteins are translated from a single bicistronic mRNA and overlap each
      other but neither overlaps ORF1. The recent determination of the 3D crystal
      structure of the HEV capsid protein should facilitate the development of vaccines
      and antivirals. The identification and characterization of animal strains of HEV
      from pigs and chickens and the demonstrated ability of cross-species infection by
      swine HEV raise public health concerns for zoonosis. Accumulating evidence
      indicated that hepatitis E is a zoonotic disease and pigs and more likely other
      animal species are reservoirs for HEV. This article provides an overview of the
      recent advances in hepatitis E and its causative agent, including nomenclature
      and genomic organization, gene expression and functions, 3D structure of the
      virions, changing perspectives on higher mortality during pregnancy and chronic
      hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal
      models.

PMID- 20040047
TI  - Treat the bones and get less rejection!

PMID- 20040048
TI  - The spectrum of renal lesions in patients with cirrhosis: a clinicopathological
      study.
AB  - BACKGROUND/OBJECTIVE: Little is known on the morphological changes in the kidneys
      of cirrhotic patients with abnormal urinalysis and/or high serum creatinine
      levels. This retrospective, one-point-in-time study aimed to report the results
      of the analysis of renal biopsy specimens obtained in patients with cirrhosis.
      METHODS: We retrieved information on 65 patients who underwent transvenous renal
      biopsy for proteinuria >0.5 g/day and/or microscopic haematuria and/or
      unexplained renal impairment (defined by serum creatinine levels >1.5 mg/dl).
      RESULTS: Fifty-one per cent of the patients had proteinuria >0.5 g/day, 58% had
      haematuria and 83% had renal impairment. Renal biopsy disclosed injury to
      glomeruli in 77% of the patients, to vessels in 69% and to the tubulointerstitium
      system in 94% (chronic in 77%; acute in 75%). Fibrous endarteritis was the most
      common renal vascular lesion. Injuries to different structures were frequently
      combined. Isolated glomerular alterations were found in only two patients. Acute
      tubular necrosis was significantly more common in patients with fibrous
      endarteritis than in those without. Among 18 patients with renal impairment,
      proteinuria <0.5 mg/day and no haematuria, 10 had glomerular lesions, 13 had
      chronic tubulointerstitial lesions and 12 acute tubulointerstitial lesions.
      CONCLUSION: In patients with cirrhosis, various types of renal injuries are
      frequently combined. Chronic lesions (vascular or tubulointerstitial) may
      influence the outcome, in particular in patients who subsequently undergo liver
      transplantation and receive anticalcineurins. Renal vascular lesions may increase
      the risk of acute tubular necrosis. In patients with renal impairment, the
      absence of significant proteinuria and haematuria do not rule out the presence of
      renal lesions.

PMID- 20040049
TI  - Hepatitis C and diabetes: one treatment for two diseases?
AB  - Abstract Epidemiological data clearly indicate a link between chronic hepatitis C
      (CHC) and disturbed glucose homeostasis. The prevalences of both type 2 diabetes
      mellitus (T2DM) and insulin resistance (IR) are higher among those chronically
      infected with hepatitis C when compared with the general population and those
      with other causes of chronic liver disease. Both IR and diabetes are associated
      with adverse outcomes across all stages of CHC including the liver transplant
      population. The adverse effects that directly influence patient outcome are
      reduced responsiveness to antiviral therapy, more rapid progression of fibrosis
      to cirrhosis and a higher incidence of hepatocellular carcinoma. Although both
      viral and host factors are known to contribute to IR (and therefore the risk of
      T2DM), there is a paucity of evidence to support interventions targeting IR with
      pharmacotherapy or lifestyle intervention. The purpose of this review is to
      examine the impact of abnormalities of glucose homeostasis in CHC, and in so
      doing, to raise a number of questions. How do we identify those at risk of
      diabetes in CHC? Can we reduce the incidence of hepatoma and reduce transplant
      related morbidity and mortality by preventing or treating diabetes? Can we
      improve the response to antiviral therapy by pretreating IR and T2DM in treatment
      candidates? Ultimately, can we cure two diseases, diabetes and CHC, with one
      treatment?

PMID- 20040051
TI  - Models of influence in chronic liver disease.
AB  - BACKGROUND & AIMS: Liver disease is often characterized by an intricate network
      of multiple, simultaneously interacting factors with organ-specific, as well as
      systemic effects. The aim of the present study is to introduce a new mathematical
      model on how to weigh a variety of factors contributing to chronic liver disease
      by the relevance of their influence on the overall disease processes. METHODS:
      Liver disease is modelled as the interaction of multiple internal and external
      factors. Each factor can potentially interact with any of the other factors in
      the model. The strength of interactions is expressed as per cent. The sum of all
      interactions contributing to each individual factor adds up to 100%. This model
      corresponds mathematically to a transposed Markov matrix. The analysis uses the
      two examples of hepatitis C virus (HCV) and autoimmune hepatitis (AIH). RESULTS:
      Impaired liver function is the most influential factor and increases in relevance
      as the degree of hepatic fibrosis increases. The relative importance of treating
      the primary disease process (HCV or AIH) diminishes as fibrosis develops.
      Similarly, psychosocial factors become less important with disease progression.
      Liver transplant is most important for Child's C cirrhosis. It is relatively
      influential for the early phase of AIH but not HCV, reflecting the fact that some
      cases of non-cirrhotic AIH can progress rapidly to acute liver failure.
      CONCLUSION: In a disease process characterized by a large array of multiple
      interacting factors, the decision tool of a transposed Markov chain helps to sort
      the contributing factors by the magnitude of their influence.

PMID- 20040050
TI  - Gene profiling of maternal hepatic adaptations to pregnancy.
AB  - BACKGROUND: Maternal metabolic demands change dramatically during the course of
      gestation and must be co-ordinated with the needs of the developing placenta and
      fetus. The liver is critically involved in metabolism and other important
      functions. However, maternal hepatic adjustments to pregnancy are poorly
      understood. AIM: The aim of the study was to evaluate the influences of pregnancy
      on the maternal liver growth and gene expression profile. METHODS: Holtzman
      Sprague-Dawley rats were mated and sacrificed at various stages of gestation and
      post-partum. The maternal livers were analysed in gravimetric response, DNA
      content by PicoGreen dsDNA quantitation reagent, hepatocyte ploidy by flow
      cytometry and hepatocyte proliferation by ki-67 immunostaining. Gene expression
      profiling of non-pregnant and gestation d18.5 maternal hepatic tissue was
      analysed using a DNA microarray approach and partially verified by northern blot
      or quantitative real-time PCR analysis. RESULTS: During pregnancy, the liver
      exhibited approximately an 80% increase in size, proportional to the increase in
      body weight of the pregnant animals. The pregnancy-induced hepatomegaly was a
      physiological event of liver growth manifested by increases in maternal hepatic
      DNA content and hepatocyte proliferation. Pregnancy did not affect hepatocyte
      polyploidization. Pregnancy-dependent changes in hepatic expression were noted
      for a number of genes, including those associated with cell proliferation,
      cytokine signalling, liver regeneration and metabolism. CONCLUSIONS: The
      metabolic demands of pregnancy cause marked adjustments in maternal liver
      physiology. Central to these adjustments are an expansion in hepatic capacity and
      changes in hepatic gene expression. Our findings provide insights into pregnancy
      dependent hepatic adaptations.

PMID- 20040052
TI  - Cell-mediated immune responses to alpha-fetoprotein and other antigens in
      hepatocellular carcinoma.
AB  - Cell-mediated immune responses play an important role in the control of tumour
      growth. CD4 and CD8 T cells recognise tumour antigens presented via major
      histocompatibility complex molecules of antigen presenting cells and develop into
      effector cells with the ability to identify and kill tumour cells. Here, we re
      examine the adaptive immune response to tumour antigens expressed by
      hepatocellular carcinoma (HCC) and discuss approaches that could be applied in
      future T-cell-based immunotherapy schedules to induce a potent and effective
      antitumour immunity. Moreover, we discuss cytotoxic T lymphocyte and Th1
      responses to tumour antigens in patients with HCC and evaluate the effects of
      conventional treatments on antitumour T-cell responses.

PMID- 20040053
TI  - Association of exogenous insulin or sulphonylurea treatment with an increased
      incidence of hepatoma in patients with hepatitis C virus infection.
AB  - BACKGROUND: Diabetes mellitus is frequently seen in hepatitis C patients and is
      often treated with antidiabetic agents that increase serum insulin levels.
      Because insulin is a growth-promoting hormone, antidiabetic agents could pose a
      risk for hepatocellular carcinoma (HCC). AIM: The aim of this study was to
      investigate an association between antidiabetic therapies and the incidence of
      HCC in hepatitis C patients with diabetes mellitus. METHODS: A nested case
      control study was conducted. Participants were recruited from a cohort study, in
      which patients with hepatitis C were consecutively registered. Participants were
      assigned to an HCC group (n=138) or a non-HCC group (n=103). To identify
      independent factors, variables including use of antidiabetic agents were analysed
      by logistic regression analysis. RESULTS: Besides ageing, being male, cirrhosis
      and hypoalbuminaemia, use of exogenous insulin and a second-generation
      sulphonylurea were significant independent factors associated with an incidence
      of HCC [odds ratio (OR) 2.969, 95% confidence interval (CI) 1.293-6.819, P<0.0103
      and OR 6.831, 95% CI 1.954-23.881, P<0.0026 respectively). In stratified
      analyses, the impact of these antidiabetic agents was more evident in patients
      who were non-cirrhotic than in those who were cirrhotic. CONCLUSIONS: Exogenous
      insulin and a second-generation sulphonylurea were independent variables
      associated with an incidence of HCC in hepatitis C patients with diabetes
      mellitus. This association was evident in patients who were non-cirrhotic. To
      verify a causal relationship between these antidiabetic agents and the
      development of HCC, a prospective cohort study is required.

PMID- 20040054
TI  - Peer mentoring in doctor performance assessment: strategies, obstacles and
      benefits.
AB  - CONTEXT: Mentors are increasingly involved in doctor performance assessments.
      Mentoring seems to be a key determinant in achieving the ultimate goal of those
      assessments, namely, improving doctor performance. Little is known, however,
      about how mentors perceive and fulfil this role. OBJECTIVE: The aim of this paper
      is to expand understanding of the role of mentors in performance assessment.
      METHODS: Thirty-eight mentors undertook formative performance assessments of
      their peers in a pilot study. A mixed-methods design was used, consisting of a
      postal survey (n = 28) and qualitative interviews with a subset of mentors (n =
      11). Individual semi-structured interviews were completed and transcripts were
      analysed by two researchers using a grounded theory approach. RESULTS: The
      results of the survey showed that 89% of mentors intended to continue in their
      mentorship role. Interviews revealed that mentors used several strategies in the
      assessments, including: contrasting and collating information; posing reflective
      questions, and goal setting. Mentors experienced difficulty in disregarding their
      views of the doctors evaluated. Some mentors noticed obstacles with specific
      interview skills such as 'paying attention to their colleagues' strengths' and
      'enabling doctors to find their own solutions'. Mentors reported that they and
      their organisations benefited from the assessments. The perceived benefits
      included: improved interview skills; increased solidarity, and increased mutual
      respect. CONCLUSIONS: The study provides insights into what mentors can do to
      increase the chance that externally derived information is integrated into
      doctors' self-assessments. Mainly, mentors used strategies aimed at effectively
      delivering feedback and encouraging reflection. However, we found that mentors
      who took part in our study appeared to struggle with a number of obstacles
      related to: time investment; familiarity with the doctor assessed, and the
      acquiring of specific interview skills.

PMID- 20040055
TI  - Means of improving medical students' prescribing skills.

PMID- 20040056
TI  - Peer teaching: a randomised controlled trial using student-teachers to teach
      musculoskeletal ultrasound.
AB  - OBJECTIVES: This study (a post-intervention assessment) was designed to assess
      the effectiveness of peer-assisted learning (PAL) using student-teachers (STs)
      with limited training to teach complicated technical skills for interpreting
      ultrasound images of the shoulder. METHODS: Students in Years 3 and 4 of medical
      school were randomly assigned to two groups. In the PAL group (PG), teaching was
      delivered by a group of nine STs from Years 3 and 4, who undertook a 30-minute
      general training and 1 week of self-teaching. In the staff-led group (SG),
      students were taught by a group of three ultrasound-experienced doctors. Exposure
      took place in two separate lessons (each of 120 minutes) and introduced eight
      standard sectional planes (EULAR) using a 10-MHz Nemio XG system (Toshiba Medical
      Systems GmbH). The theoretical and practical learning outcomes were tested using
      a multiple-choice question (MCQ) test and an objective structured clinical
      examination (OSCE). Qualitative differences were evaluated using Likert scale
      based items. RESULTS: Evaluation of differences between the PG (n = 75) and SG (n
      = 76) in the theoretical (MCQ score; P = 0.644) and practical (total OSCE score;
      P = 0.133) outcomes showed no difference between the two groups. However, the STs
      themselves showed significantly better results overall (P < 0.05). Staff members
      were rated more highly than STs, especially on items relating to competence (P <
      0.05). CONCLUSIONS: Complicated technical skills can be adequately taught to
      students using the PAL system by STs with limited training. Self-teaching
      learning strategies are successful in contexts of limited teacher training.
      However, despite positive objective results, STs still face prejudice from
      students with regard to competency.

PMID- 20040057
TI  - The ties that bind: a network approach to creating a programme in faculty
      development.
AB  - CONTEXT: Current trends in medical education reflect the changing health care
      environment. An increasingly large and diverse student population, a move to more
      distributed models of education, greater community involvement and an emphasis on
      social accountability, interprofessional education and student-centred approaches
      to learning necessitate new approaches to faculty development to help faculty
      members respond effectively to this rapidly changing landscape. METHODS: Drawing
      upon the tenets of network theory and the broader organisational literature, we
      propose a 'fishhook' model of faculty development programme formation. The model
      is based on seven key factors which supported the successful formation of a
      centralised programme for faculty development that addressed many of the
      contemporary issues in medical education. These factors include: environmental
      readiness; commitment and vision of a mobiliser; recruitment of key stakeholders
      and leaders to committees; formation of a collaborative network structure;
      accumulation of networking capital; legitimacy, and flexibility. DISCUSSION: Our
      aim in creating this model is to provide a guide for other medical schools to
      consider when developing similar programmes. The model can be adapted to reflect
      the local goals, settings and cultures of other medical education contexts.

PMID- 20040058
TI  - Diverticular disease is associated with an enteric neuropathy as revealed by
      morphometric analysis.
AB  - BACKGROUND: The pathogenesis of diverticular disease (DD) is attributed to
      several aetiological factors (e.g. age, diet, connective tissue disorders) but
      also includes distinct intestinal motor abnormalities. Although the enteric
      nervous system (ENS) is the key-regulator of intestinal motility, data on
      neuropathological alterations are limited. The study aimed to investigate the ENS
      by a systematic morphometric analysis. METHODS: Full-thickness sigmoid specimens
      obtained from patients with symptomatic DD (n = 27) and controls (n = 27) were
      processed for conventional histology and immunohistochemistry using anti-HuC/D as
      pan-neuronal marker. Enteric ganglia, nerve and glial cells were quantified
      separately in the myenteric, external and internal submucosal plexus
      compartments. KEY RESULTS: Compared to controls, patients with DD showed
      significantly (P < 0.05) (i) reduced neuronal density in all enteric nerve
      plexus, (ii) decrease of ganglionic nerve cell content in the myenteric plexus,
      (iii) decreased ganglionic density in the internal submucosal plexus, (iv)
      reduced glial cell density in the myenteric plexus, (v) decrease of ganglionic
      glial cell content in the myenteric plexus and increase in submucosal plexus
      compartments, (vi) increased glia index in all enteric nerve plexus. About 44.4%
      of patients with DD exhibited myenteric ganglia displaying enteric gliosis.
      CONCLUSIONS & INFERENCES: Patients with DD show substantial structural
      alterations of the ENS mainly characterized by myenteric and submucosal oligo
      neuronal hypoganglionosis which may account for intestinal motor abnormalities
      reported in DD. The morphometric data give evidence that DD is associated with
      structural alterations of the ENS which may complement established pathogenetic
      concepts.

PMID- 20040059
TI  - Delayed gastric emptying and disruption of the interstitial cells of Cajal
      network after gastric ischaemia and reperfusion.
AB  - BACKGROUND: Gastrointestinal tract is one of the most susceptible organ systems
      to ischaemia. Not only mucosal injury but also alterations of the intestinal
      motility and loss of interstitial cells of Cajal (ICC) have been reported in
      response to ischaemia and reperfusion (I/R). However, there are few reports on
      the changes in the gastric motility after gastric I/R. The present study was
      designed to investigate the alterations in gastric emptying, the ICC and enteric
      nerves that regulate smooth muscle function in response to gastric I/R. METHODS:
      Seven-week-old male Wistar rats were exposed to gastric I/R, and the gastric
      emptying rates at 12 and 48 h after I/R were evaluated by the phenol red method.
      Expressions of gene product of c-kit receptor tyrosine kinase (c-Kit), a marker
      of ICC, and of neuronal proteins were also examined. KEY RESULTS: Gastric
      emptying was transiently delayed at 12 h after I/R, but returned to normal by 48
      h. Expression of c-Kit protein as assessed by Western blotting and
      immunofluorescent staining of the smooth muscle layer, as well as expression of
      the mRNA of stem cell factor, the ligand for c-Kit, were reduced at both 12 and
      48 h after I/R. The expression of neuronal nitric oxide synthase (nNOS) protein
      as assessed by Western blotting and immunofluorescent staining was also decreased
      at 12 h after I/R, but was restored to normal by 48 h. CONCLUSIONS & INFERENCES:
      Gastric I/R evokes transient gastroparesis with delayed gastric emptying,
      associated with disruption of the ICC network and nNOS-positive neurons.

PMID- 20040060
TI  - Resistance and biomass in Arabidopsis: a new model for salicylic acid perception.
AB  - Salicylic acid (SA) is an essential hormone for plant defence and development. SA
      perception is usually measured by counting the number of pathogens that grow in
      planta upon an exogenous application of the hormone. A biological SA perception
      model based on plant fresh weight reduction caused by disease resistance in
      Arabidopsis thaliana is proposed. This effect is more noticeable when a chemical
      analogue of SA is used, like Benzothiadiazole (BTH). By spraying BTH several
      times, a substantial difference in plant biomass is observed when compared with
      the mock treatment. Such difference is dose-dependent and does not require
      pathogen inoculation. The model is robust and allows for the comparison of
      different Arabidopsis ecotypes, recombinant inbreed lines, and mutants. Our
      results show that two mutants, non-expresser of pathogenesis-related genes 1
      (npr1) and auxin resistant 3 (axr3), fail to lose biomass when BTH is applied to
      them. Further experiments show that axr3 responds to SA and BTH in terms of
      defence induction. NPR1-related genotypes also confirm the pivotal role of NPR1
      in SA perception, and suggest an active program of depletion of resources in the
      infected tissues.

PMID- 20040061
TI  - Increasing inositol (1,4,5)-trisphosphate metabolism affects drought tolerance,
      carbohydrate metabolism and phosphate-sensitive biomass increases in tomato.
AB  - Inositol-(1,4,5)-trisphosphate (InsP(3)) is a second messenger in plants that
      increases in response to many stimuli. The metabolic consequences of this
      signalling pathway are not known. We reduced the basal level of InsP(3) in tomato
      (Solanum lycopersicum cv. Micro-Tom) by expressing the human type I inositol
      polyphosphate 5-phosphatase (InsP 5-ptase) gene. Transgenic lines producing InsP
      5-ptase protein had between 15% and 30% of the basal InsP(3) level of control
      plants. This increased hydrolysis of InsP(3) caused dramatic increases in drought
      tolerance, vegetative biomass and lycopene and hexose concentrations in the
      fruits. Transcript profiling of root, leaf and fruit tissues identified a small
      group of genes, including a cell-wall invertase inhibitor gene, that were
      differentially regulated in all tissues of the InsP 5-ptase expressing plants.
      Significant differences were found in the amounts of carbohydrates and organic
      phosphate in these plants. Plants with increased hydrolysis of InsP(3) in the
      cytosol also showed increased net CO(2)-fixation and sucrose export into sink
      tissue and storage of hexoses in the source leaves. The increase in biomass was
      dependent on the supply of inorganic phosphate in the nutrient medium. Uptake and
      storage of phosphate was increased in the transgene expressing lines. This
      suggests that in tomato, increased flux through the inositol phosphate pathway
      uncoupled phosphate sensing from phosphate metabolism. Altering the second
      messenger, InsP(3), revealed multiple coordinated changes in development and
      metabolism in tomato that have potential for crop improvement.

PMID- 20040062
TI  - The Arabidopsis gene SIGMA FACTOR-BINDING PROTEIN 1 plays a role in the
      salicylate- and jasmonate-mediated defence responses.
AB  - The chloroplast-localized SIB1 protein was previously identified by its
      interaction with SIGMA FACTOR 1 (SIG1), a component of the RNA polymerase
      machinery responsible for transcription of plastid genes. The physiological
      function of SIB1 is little known. We found that expression of SIB1 is induced by
      infection with Pseudomonas syringae, suggesting its possible involvement in the
      defence response. The sib1 loss-of-function mutation compromises induction of
      some defence-related genes triggered by pathogen infection and the treatments
      with salicylic acid (SA) and jasmonic acid (JA), two key signalling molecules in
      the defence response. Conversely, constitutive over-expression of SIB1 causes the
      plants to hyper-activate defence-related genes following pathogen infection or
      the SA and JA treatments, leading to enhanced resistance to infection by P.
      syringae. SIB1 is a member of the large plant-specific VQ motif-containing
      protein family, and might act as a link to connect defence signalling with
      chloroplast function.

PMID- 20040063
TI  - Signal transduction in Mimosa pudica: biologically closed electrical circuits.
AB  - Biologically closed electrical circuits operate over large distances in
      biological tissues. The activation of such circuits can lead to various
      physiological and biophysical responses. Here, we analyse the biologically closed
      electrical circuits of the sensitive plant Mimosa pudica Linn. using
      electrostimulation of a petiole or pulvinus by the charged capacitor method, and
      evaluate the equivalent electrical scheme of electrical signal transduction
      inside the plant. The discharge of a 100 microF capacitor in the pulvinus
      resulted in the downward fall of the petiole in a few seconds, if the capacitor
      was charged beforehand by a 1.5 V power supply. Upon disconnection of the
      capacitor from Ag/AgCl electrodes, the petiole slowly relaxed to the initial
      position. The electrical properties of the M. pudica were investigated, and an
      equivalent electrical circuit was proposed that explains the experimental data.

PMID- 20040064
TI  - Drought and salt tolerances in wild relatives for wheat and barley improvement.
AB  - Drought and salinity are the major abiotic stresses that dramatically threaten
      the food supply in the world. Tribe Triticeae, including wheat and barley,
      possesses tremendous potential for drought and salt tolerance that has been
      extensively and practically identified, tested, and transferred to wheat
      cultivars with proven expression of tolerance in experimental trials. Triticum
      dicoccoides and Hordeum spontaneum, the progenitors of cultivated wheat and
      barley, have adapted to a broad range of environments and developed rich genetic
      diversities for drought and salt tolerances. Drought- and salt-tolerant genes and
      quantitative trait loci (QTLs) have been identified in T. dicoccoides and H.
      spontaneum and have great potential in wheat and barley improvement. Advanced
      backcross QTL analysis, the introgression libraries based on wild wheat and wild
      barley as donors, and positional cloning of natural QTLs will play prevailing
      roles in elucidating the molecular control of drought and salt tolerance.
      Combining tolerant genes and QTLs in crop breeding programs aimed at improving
      tolerance to drought and salinity will be achieved within a multidisciplinary
      context. Wild genetic resistances to drought and salinity will be shifted in the
      future from field experiments to the farmer.

PMID- 20040065
TI  - ACO1, a gene for aminocyclopropane-1-carboxylate oxidase: effects on internode
      elongation at the heading stage in rice.
AB  - Although reports on a gene for 1-amino-cyclopropane-1-carboxylate (ACC) oxidase
      (ACO1) in rice (Oryza sativa L.) suggest that high levels of its transcript are
      associated with internode elongation of deep-water rice during submergence, the
      role of ACO1 in rice development is largely unknown. The tissue-specificity of
      ACO1 expression indicated that its transcript significantly accumulated in lower
      parts of elongating internodes at the heading stage. Histochemical analysis and
      in situ hybridization showed that the ACO1 expression was localized in the basal
      parts of leaf sheaths immediately above nodes or the lower parts of elongating
      internodes. To further examine the role of ACO1, ACO1-deficient (aco1) and
      overexpressing (ACO1-OX) mutants were characterized. The total length of the
      elongated internodes of aco1 mutants was slightly shorter than that of wild-type
      plants and that of ACO1-OX mutants was longer. Interestingly, expression of the
      ACC synthase gene ACS1 and ethylene signalling gene OsEIN2 was up-regulated in
      the aco1 mutants. This study suggests that the ACO1 has a little effect on
      internode elongation at the heading stage, and that up-regulation of the ACS1 and
      OsEIN2 expression may attenuate inhibition of internode elongation.

PMID- 20040066
TI  - Variation in salinity tolerance and shoot sodium accumulation in Arabidopsis
      ecotypes linked to differences in the natural expression levels of transporters
      involved in sodium transport.
AB  - Salinity tolerance can be attributed to three different mechanisms: Na+ exclusion
      from the shoot, Na+ tissue tolerance and osmotic tolerance. Although several key
      ion channels and transporters involved in these processes are known, the
      variation in expression profiles and the effects of these proteins on Na+
      transport in different accessions of the same species are unknown. Here,
      expression profiles of the genes AtHKT1;1, AtSOS1, AtNHX1 and AtAVP1 are
      determined in four ecotypes of Arabidopsis thaliana. Not only are these genes
      differentially regulated between ecotypes, the expression levels of the genes can
      be linked to the concentration of Na+ in the plant. An inverse relationship was
      found between AtSOS1 expression in the root and total plant Na+ accumulation,
      supporting a role for AtSOS1 in Na+ efflux from the plant. Similarly, ecotypes
      with high expression levels of AtHKT1;1 in the root had lower shoot Na+
      concentrations, due to the hypothesized role of AtHKT1;1 in retrieval of Na+ from
      the transpiration stream. The inverse relationship between shoot Na+
      concentration and salinity tolerance typical of most cereal crop plants was not
      demonstrated, but a positive relationship was found between salt tolerance and
      levels of AtAVP1 expression, which may be related to tissue tolerance.

PMID- 20040067
TI  - Determination of de novo and pool emissions of terpenes from four common
      boreal/alpine trees by 13CO2 labelling and PTR-MS analysis.
AB  - Boreal forests emit a large amount of monoterpenes into the atmosphere.
      Traditionally these emissions are assumed to originate as evaporation from large
      storage pools. Thus, their diurnal cycle would depend mostly on temperature.
      However, there is indication that a significant part of the monoterpene emission
      would originate directly from de novo synthesis. By applying 13CO2 fumigation and
      analyzing the isotope fractions with proton transfer reaction mass spectrometry
      (PTR-MS) and classical GC-MS, we determined the fractions of monoterpene
      emissions originating from de novo biosynthesis in Pinus sylvestris (58%), Picea
      abies (33.5%), Larix decidua (9.8%) and Betula pendula (100%). Application of the
      observed split between de novo and pool emissions from P. sylvestris in a hybrid
      emission algorithm resulted in a better description of ecosystem scale
      monoterpene emissions from a boreal Scots pine forest stand.

PMID- 20040068
TI  - Role of aquaporins in root water transport of ectomycorrhizal jack pine (Pinus
      banksiana) seedlings exposed to NaCl and fluoride.
AB  - Effects of ectomycorrhizal (ECM) fungus Suillus tomentosus on water transport
      properties were studied in jack pine (Pinus banksiana) seedlings. The hydraulic
      conductivity of root cortical cells (L(pc)) and of the whole root system (L(pr))
      in ECM plants was higher by twofold to fourfold compared with the non-ECM
      seedlings. HgCl2 had a greater inhibitory effect on L(pc) in ECM compared with
      non-ECM seedlings, suggesting that the mercury-sensitive, aquaporin (AQP)
      mediated water transport was largely responsible for the differences in L(pc)
      between the two groups of plants. L(pc) was rapidly and drastically reduced by
      the 50 mM NaCl treatment. However, in ECM plants, the initial decline in L(pc)
      was followed by a quick recovery to the pre-treatment level, while the reduction
      of L(pc) in non-ECM seedlings progressed over time. Treatments with fluoride
      reduced L(pc) by about twofold in non-ECM seedlings and caused smaller reductions
      of L(pc) in ECM plants. When either 2 mM KF or 2 mM NaF were added to the 50 mM
      NaCl treatment solution, the inhibitory effect of NaCl on L(pc) was rapidly
      reversed in both groups of plants. The results suggest that AQP-mediated water
      transport may be linked to the enhancement of salt stress resistance reported for
      ECM plants.

PMID- 20040069
TI  - Age at onset in 3014 Sardinian bipolar and major depressive disorder patients.
AB  - OBJECTIVE: To test if onset age in major affective illnesses is younger in
      bipolar disorder (BPD) than unipolar-major depressive disorder (UP-MDD), and is a
      useful measure. METHOD: We evaluated onset-age for DSM-IV-TR major illnesses in
      3014 adults (18.5% BP-I, 12.5% BP-II, 69.0% UP-MDD; 64% women) at a mood
      disorders center. RESULTS: Median and interquartile range (IQR) onset-age ranked:
      BP-I = 24 (19-32) < BP-II = 29 (20-40) < UP-MDD = 32 (23-47) years (P < 0.0001),
      and has remained stable since the 1970s. In BP-I patients, onset was latest for
      hypomania, and depression presented earlier than in BP-II or UP-MDD cases.
      Factors associated with younger onset included: i) being unmarried, ii) more
      education, iii) BPD-diagnosis, iv) family-history, v) being employed, vi) ever
      suicidal, vii) substance-abuse and viii) ever-hospitalized. Onset-age
      distinguished BP-I from UP-MDD depressive onsets with weak sensitivity and
      specificity. CONCLUSION: Onset age was younger among BPD than MDD patients, and
      very early onset may distinguish BPD vs. UP-MDD with depressive-onset.

PMID- 20040070
TI  - Sanfilippo B in an elderly female psychiatric patient: a rare but relevant
      diagnosis in presenile dementia.
AB  - OBJECTIVE: Sanfilippo B is a rare autosomal recessive mucopolysaccharidosis (MPS
      IIIB) caused by a deficiency of N-acetyl-alpha-D-glucosaminidase (NAGLU). METHOD:
      A mild mentally retarded elderly female patient is described with a slowly
      progressive dementia who had given birth to a daughter who developed normally.
      RESULTS: Metabolic screening revealed an enhanced concentration of heparan
      sulfate in urine. Enzymatic assay demonstrated deficiency of N-acetyl-alpha-D
      glucosaminidase. Mutations in the NAGLU gene were found. One mentally retarded
      and hospitalized elder brother was also found to have MPS IIIB, whereas a second
      brother, who had died earlier, is suspected to have had the same metabolic
      disorder. Prior to the development of dementia, both the patient and her brother
      showed autistic like features, signs of ideomotor apraxia and weakness in verbal
      comprehension. CONCLUSION: Screening for metabolic disorders, in particular
      MPSes, should always be considered in patients with a history of mental deficit
      and dementia or progressive functional decline.

PMID- 20040071
TI  - Sanfilippo B in an elderly female psychiatric patient: a rare but relevant
      diagnosis in presenile dementia.(Invited comment.

PMID- 20040072
TI  - Feeding infants with CHD with breast milk: Norwegian Mother and Child Cohort
      Study.
AB  - OBJECTIVE: To explore the prevalence of breast milk feeding (BMF) of infants with
      congenital heart defects (CHD) during first 6 months of life, as compared with
      general population. DESIGN: The study is based on a subsample of the Norwegian
      Mother and Child Cohort Study conducted by Norwegian Institute of Public Health.
      A total of 60,600 mothers completed a questionnaire about infant feeding at 6
      months postpartum. Infants with moderate/severe CHD (n = 131) were identified
      using nationwide CHD registry. A group of infants with CHD with comorbidity was
      also defined (n = 65). BMF was classified as predominant, continued, or no BMF.
      Month to month feeding status was analysed by means of Cox regression analyses.
      RESULTS: Between child age 2-6 months, mothers of infants with CHD had a hazard
      ratio (HR) of 1.69 of weaning their child compared with mothers of controls.
      Mothers of infants with CHD with comorbidity weaned at an even faster rate (HR
      3.54). At age 6 months, 9.9% of infants with CHD were fed with breast milk
      predominately, 64.1% continued to receive breast milk, and only 26% were fed no
      breast milk. For infants with CHD with comorbidity, corresponding percentages
      were 7.7%, 43.1% and 49.2%, respectively. CONCLUSIONS: Although CHD alone and
      particularly CHD with comorbidity increased risk that mothers wean earlier, a
      relatively high rate of continued breastfeeding was maintained. Future studies
      should investigate factors that support continued BMF even in the most severely
      affected children with CHD.

PMID- 20040073
TI  - Identifying problematic severe asthma in the individual child--does lung function
      matter?
AB  - AIM: Measures of lung function (usually FEV(1) <80% predicted) are used to
      classify asthma severity in both adults and children, despite evidence that lung
      function impairment is less pronounced in the paediatric asthma population. The
      present study assesses the relevance of lung function measurements as
      discriminators of severe childhood asthma. METHODS: Fifty-one school-aged
      children with problematic severe asthma, 37 mild-to-moderate asthmatics and 29
      healthy controls underwent a comprehensive clinical work-up. Problematic severe
      asthma was defined in patients exhibiting poor asthma control despite high-dose
      inhaled corticosteroid treatment and at least one other asthma controller drug.
      Mild-to-moderate asthmatic children used low-dose inhaled steroids and reported
      minimal asthma symptoms. RESULTS: Baseline FEV(1) values were significantly
      reduced in children with problematic severe asthma, yet FEV(1) <80% predicted
      showed a low sensitivity (41%) for discriminating severe vs. mild-to-moderate
      asthma. Receiver-operated characteristic analysis estimated the optimal cut-off
      of FEV(1) to be 90% predicted in this population (sensitivity 61%, specificity
      83%). Baseline FEV(1)/FVC and FEF(25-75) values were not superior to FEV(1) in
      discriminating problematic severe asthma, and neither exhaled nitric oxide levels
      nor bronchial hyperresponsiveness differentiated between the two asthmatic study
      populations. CONCLUSION: Spirometric measurements are insensitive discriminators
      of problematic severe asthma in childhood.

PMID- 20040075
TI  - Acute metabolic responses to a high-carbohydrate meal in outpatients with type 2
      diabetes treated with a low-carbohydrate diet: a crossover meal tolerance study.
AB  - BACKGROUND: A low-carbohydrate diet (LCD) achieves good glycemic control in type
      2 diabetes (T2DM) compared with a high-carbohydrate diet. With respect to energy
      metabolism, acute metabolic responses to high-carbohydrate meals (HCMs) have not
      been determined in LCD patients with T2DM. SUBJECTS AND METHODS: We enrolled 31
      subjects with T2DM (mean age: 62 yrs, mean hemoglobin A1c level: 6.9%), of whom
      13 were on a strict LCD (26% carbohydrate diet), and 18 a moderate one (44%
      carbohydrate diet). Two isocaloric meals were administered to all subjects in a
      randomized crossover design. The carbohydrate:protein:fat ratios of HCMs and low
      carbohydrate meals (LCMs) were 59:20:21 and 7:20:73, respectively. Serum beta
      hydroxybutyrate, acetoacetate, free fatty acids (FFAs), triglyceride and insulin,
      and plasma glucose concentrations were measured for 120 minutes after the intake
      of each meal. RESULTS: HCMs rapidly decreased postprandial beta-hydroxybutyrate,
      acetoacetate and FFA concentrations within 2 hours in all patients in combination
      with rapid increases in serum insulin and plasma glucose, while LCMs increased or
      did not change beta-hydroxybutyrate, acetoacetate and FFAs (P < 0.001 for all).
      HCMs did not change postprandial triglyceride concentrations over 2 hours, while
      LCMs gradually increased them (P < 0.001). HCMs sharply and rapidly decreased
      postprandial beta-hydroxybutyrate and acetoacetate concentrations in strict LCD
      subjects over 2 hours, but only slightly decreased them in moderate LCD subjects
      (P < 0.001, difference between strict and moderate LCD subjects). The parameter
      Deltaketone bodies (level at 120 minutes - level at baseline) was significantly
      correlated with the insulinogenic index (Spearman's r = 0.503 for beta
      hydroxybutyrate and 0.509 for acetoacetate), but not with total insulin secretory
      capacity. Moreover, HCMs slightly decreased postprandial triglyceride levels in
      strict LCD subjects but somewhat increased them in the moderate LCD subjects (P =
      0.002). The parameter Deltatriglyceride was significantly correlated with
      background dietary %carbohydrate (Spearman's r = 0.484). CONCLUSION: HCMs rapidly
      decreased postprandial ketone body concentrations in T2DM patients treated with a
      LCD. The decreases were more remarkable in strict than in moderate LCD subjects.
      HCMs slightly decreased postprandial triglyceride levels in strict LCD subjects.
      The parameter Deltaketone bodies was significantly correlated with the
      insulinogenic index, as was Deltatriglyceride with background dietary
      %carbohydrate.

PMID- 20040076
TI  - Perspectives from deductible plan enrollees: plan knowledge and anticipated care
      seeking changes.
AB  - BACKGROUND: Consumer directed health care proposes that patients will engage as
      informed consumers of health care services by sharing in more of their medical
      costs, often through deductibles. We examined knowledge of deductible plan
      details among new enrollees, as well as anticipated care-seeking changes in
      response to the deductible. METHODS: In a large integrated delivery system with a
      range of deductible-based health plans which varied in services included or
      exempted from deductible, we conducted a mixed-method, cross-sectional telephone
      interview study. RESULTS: Among 458 adults newly enrolled in a deductible plan
      (71% response rate), 51% knew they had a deductible, 26% knew the deductible
      amount, and 6% knew which medical services were included or exempted from their
      deductible. After adjusting for respondent characteristics, those with more
      deductible-applicable services and those with lower self-reported health status
      were significantly more likely to know they had a deductible. Among those who
      knew of their deductible, half anticipated that it would cause them to delay or
      avoid medical care, including avoiding doctor's office visits and medical tests,
      even services that they believed were medically necessary. Many expressed concern
      about their costs, anticipating the inability to afford care and expressing the
      desire to change plans. CONCLUSION: Early in their experience with a deductible,
      patients had limited awareness of the deductible and little knowledge of the
      details. Many who knew of the deductible reported that it would cause them to
      delay or avoid seeking care and were concerned about their healthcare costs.

PMID- 20040077
TI  - Prevalence of tick-borne encephalitis virus antibodies in dogs from Denmark.
AB  - BACKGROUND: Large regions of central and eastern Europe are recognized as areas
      where tick-borne encephalitis virus (TBEV) is endemic, including countries
      neighbouring Denmark. It is therefore timely and relevant to determine if TBEV
      infections occur in Denmark. This study investigates the presence of antibodies
      against TBEV in a cross-section of the Danish canine population to assess the
      level of exposure to TBEV and possibly identify TBEV microfoci in Denmark.
      METHODS: Blood samples were collected from 125 dogs originating from five regions
      of Denmark between November 2005 and March 2006. Serum was tested by indirect
      ELISA. All positive and borderline samples were re-evaluated by neutralisation
      test (NT). RESULTS: The prevalence of TBEV serocomplex antibodies was 30% by
      ELISA and 4.8% by NT (with 100%-neutralising capacity). The island of Bornholm
      was the only area in Denmark with NT positive samples. CONCLUSIONS: The island of
      Bornholm is an area with a high risk of encountering TBEV microfoci. The presence
      of TBEV serocomplex antibodies in many sentinel animals from other parts of
      Denmark points toward existence of other TBEV microfoci. Discrepancies found
      between ELISA and NT results stress the importance of careful evaluation of
      serological tests, when interpreting results.

PMID- 20040078
TI  - aes, the gene encoding the esterase B in Escherichia coli, is a powerful
      phylogenetic marker of the species.
AB  - BACKGROUND: Previous studies have established a correlation between
      electrophoretic polymorphism of esterase B, and virulence and phylogeny of
      Escherichia coli. Strains belonging to the phylogenetic group B2 are more
      frequently implicated in extraintestinal infections and include esterase B2
      variants, whereas phylogenetic groups A, B1 and D contain less virulent strains
      and include esterase B1 variants. We investigated esterase B as a marker of
      phylogeny and/or virulence, in a thorough analysis of the esterase B-encoding
      gene. RESULTS: We identified the gene encoding esterase B as the acetyl-esterase
      gene (aes) using gene disruption. The analysis of aes nucleotide sequences in a
      panel of 78 reference strains, including the E. coli reference (ECOR) strains,
      demonstrated that the gene is under purifying selection. The phylogenetic tree
      reconstructed from aes sequences showed a strong correlation with the species
      phylogenetic history, based on multi-locus sequence typing using six housekeeping
      genes. The unambiguous distinction between variants B1 and B2 by electrophoresis
      was consistent with Aes amino-acid sequence analysis and protein modelling, which
      showed that substituted amino acids in the two esterase B variants occurred
      mostly at different sites on the protein surface. Studies in an experimental
      mouse model of septicaemia using mutant strains did not reveal a direct link
      between aes and extraintestinal virulence. Moreover, we did not find any genes in
      the chromosomal region of aes to be associated with virulence. CONCLUSION: Our
      findings suggest that aes does not play a direct role in the virulence of E. coli
      extraintestinal infection. However, this gene acts as a powerful marker of
      phylogeny, illustrating the extensive divergence of B2 phylogenetic group strains
      from the rest of the species.

PMID- 20040081
TI  - Persistence of accuracy of genome-wide breeding values over generations when
      including a polygenic effect.
AB  - BACKGROUND: When estimating marker effects in genomic selection, estimates of
      marker effects may simply act as a proxy for pedigree, i.e. their effect may
      partially be attributed to their association with superior parents and not be
      linked to any causative QTL. Hence, these markers mainly explain polygenic
      effects rather than QTL effects. However, if a polygenic effect is included in a
      Bayesian model, it is expected that the estimated effect of these markers will be
      more persistent over generations without having to re-estimate the marker effects
      every generation and will result in increased accuracy and reduced bias. METHODS:
      Genomic selection using the Bayesian method, 'BayesB' was evaluated for different
      marker densities when a polygenic effect is included (GWpEBV) and not included
      (GWEBV) in the model. Linkage disequilibrium and a mutation drift balance were
      obtained by simulating a population with a Ne of 100 over 1,000 generations.
      RESULTS: Accuracy of selection was slightly higher for the model including a
      polygenic effect than for the model not including a polygenic effect whatever the
      marker density. The accuracy decreased in later generations, and this reduction
      was stronger for lower marker densities. However, no significant difference in
      accuracy was observed between the two models. The linear regression of TBV on
      GWEBV and GWpEBV was used as a measure of bias. The regression coefficient was
      more stable over generations when a polygenic effect was included in the model,
      and was always between 0.98 and 1.00 for the highest marker density. The
      regression coefficient decreased more quickly with decreasing marker density.
      CONCLUSIONS: Including a polygenic effect had no impact on the selection
      accuracy, but showed reduced bias, which is especially important when estimates
      of genome-wide markers are used to estimate breeding values over more than one
      generation.

PMID- 20040079
TI  - Comprehensive in silico prediction and analysis of chlamydial outer membrane
      proteins reflects evolution and life style of the Chlamydiae.
AB  - BACKGROUND: Chlamydiae are obligate intracellular bacteria comprising some of the
      most important bacterial pathogens of animals and humans. Although chlamydial
      outer membrane proteins play a key role for attachment to and entry into host
      cells, only few have been described so far. We developed a comprehensive,
      multiphasic in silico approach, including the calculation of clusters of
      orthologues, to predict outer membrane proteins using conservative criteria. We
      tested this approach using Escherichia coli (positive control) and Bacillus
      subtilis (negative control), and applied it to five chlamydial species; Chlamydia
      trachomatis, Chlamydia muridarum, Chlamydia (a.k.a. Chlamydophila) pneumoniae,
      Chlamydia (a.k.a. Chlamydophila) caviae, and Protochlamydia amoebophila. RESULTS:
      In total, 312 chlamydial outer membrane proteins and lipoproteins in 88
      orthologous clusters were identified, including 238 proteins not previously
      recognized to be located in the outer membrane. Analysis of their taxonomic
      distribution revealed an evolutionary conservation among Chlamydiae,
      Verrucomicrobia, Lentisphaerae and Planctomycetes as well as lifestyle-dependent
      conservation of the chlamydial outer membrane protein composition. CONCLUSION:
      This analysis suggested a correlation between the outer membrane protein
      composition and the host range of chlamydiae and revealed a common set of outer
      membrane proteins shared by these intracellular bacteria. The collection of
      predicted chlamydial outer membrane proteins is available at the online database
      pCOMP http://www.microbial-ecology.net/pcomp and might provide future guidance in
      the quest for anti-chlamydial vaccines.

PMID- 20040080
TI  - Plexin-B1, glycodelin and MMP7 expression in the human fallopian tube and in the
      endometrium.
AB  - BACKGROUND: To study the expression of Plexin-B1, Glycodelin, and MMP7 during the
      menstrual cycle in the endometrium and in the fallopian tube. METHODS: The
      research included women undergoing hysterectomy, tubal sterilization or salpingo
      oophoerectomy. Total RNA from endometrial and fallopian tube tissues was
      extracted using a total RNA isolation kit. Semi-quantitative RT-PCR was performed
      to examine mRNA relative expression. RESULTS: Plexin-B1 expression in the
      endometrium was significantly higher on days 19 - 23 compared to days 12 - 14
      (1.166 +/- 0.42 versus 0.523 +/- 0.299), P < 0.005. In the fallopian tube the
      level of plexin-B1 did not change significantly throughout the menstrual cycle.
      Glycodelin expression was significantly higher on days 19 - 23 compared with days
      12-14, both in the endometrium (0.819 +/- 0.564 versus 0.072 +/- 0.343, P < 0.05)
      and the fallopian tube (0.796 +/- 0.196 versus 0.329 +/- 0.398, P < 0.05).
      Although the level of MMP7 secretion was the highest in the secretory phase the
      difference from the proliferative phase did not reach statistical significance,
      neither in the endometrium nor in the fallopian tube. This could result from a
      lack of power. CONCLUSIONS: In the endometrium, both Glycodelin and Plexin-B1 are
      exhibiting a cyclic pattern suggesting a possible steroid regulation and a role
      in endometrial receptivity.

PMID- 20040082
TI  - Reduced Ca2+ transport across sarcolemma but enhanced spontaneous activity in
      cardiomyocytes isolated from left atrium-pulmonary veins tissue of myopathic
      hamster.
AB  - BACKGROUND: Several lines of evidence point to a particularly important role of
      the left atrium (LA) in initiating and maintaining atrial fibrillation (AF). This
      role may be related to the location of pulmonary veins (PVs) in the LA. The aim
      of the present study was to investigate the action potential (AP) and ionic
      currents in LA-PV cardiomyocytes isolated from Bio14.6 myopathic Syrian hamsters
      (36-57 week-old) versus age-matched F1B healthy control hamsters. METHODS AND
      RESULTS: Whole-cell patch-clamp techniques were used to record AP in current
      clamp mode and ionic currents in voltage-clamp mode. The results obtained show
      that in both healthy and myopathic LA-PV tissue spontaneously discharging
      cardiomyocytes can be found, but they are more numerous in myopathic (9/29) than
      in healthy hamsters (4/42, p < 0.05 by chi2 analysis). Myopathic myocytes have
      shorter AP duration (APD) with smaller ICa,L and INCX than the healthy control.
      The currents ITO, IK, IK1 and ICa,T are not significantly different in myopathic
      versus healthy cells. CONCLUSIONS: Our results indicate that in myopathic Syrian
      hamsters LA-PV cardiomyocytes are more prone to automatic rhythms. Also, they
      show altered electrophysiologic properties, which may be due to abnormal Ca2+
      channels and may account for contractile dysfunction.

PMID- 20040083
TI  - Allogeneic blood transfusion and prognosis following total hip replacement: a
      population-based follow up study.
AB  - BACKGROUND: Allogeneic red blood cell transfusion is frequently used in total hip
      replacement surgery (THR). However, data on the prognosis of transfused patients
      are sparse. In this study we compared the risk of complications following THR in
      transfused and non-transfused patients. METHODS: A population-based follow-up
      study was performed using data from medical databases in Denmark. We identified
      28,087 primary THR procedures performed from 1999 to 2007, from which we computed
      a propensity score for red blood cell transfusion based on detailed data on
      patient-, procedure-, and hospital-related characteristics. We were able to match
      2,254 transfused with 2,254 non-transfused THR patients using the propensity
      score. RESULTS: Of the 28,087 THR patients, 9,063 (32.3%) received at least one
      red blood cell transfusion within 8 days of surgery. Transfused patients had
      higher 90-day mortality compared with matched non-transfused patients: the
      adjusted OR was 2.2 (95% confidence interval (CI): 1.2-3.8). Blood transfusion
      was also associated with increased odds of pneumonia (OR 2.1; CI: 1.2-3.8),
      whereas the associations with cardiovascular or cerebrovascular events (OR 1.4;
      CI: 0.9-2.2) and venous thromboembolism (OR 1.2; CI: 0.7-2.1) did not reach
      statistical significance. The adjusted OR of reoperation due to infection was 0.6
      (CI: 0.1-2.9). CONCLUSIONS: Red blood cell transfusion was associated with an
      adverse prognosis following primary THR, in particular with increased odds of
      death and pneumonia. Although the odds estimates may partly reflect unmeasured
      bias due to blood loss, they indicate the need for careful assessment of the risk
      versus benefit of transfusion even in relation to routine THR procedures.

PMID- 20040084
TI  - Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy.
AB  - BACKGROUND: Although 70% (or 2/3) partial hepatectomy (PH) is the most studied
      model for liver regeneration, the hepatic protein expression profile associated
      with lower volume liver resection (such as 50% PH) has not yet been reported.
      Therefore, the aim of this study was to determine the global protein expression
      profile of the regenerating mouse liver following 50% PH by differential
      proteomics, and thereby gaining some insights into the hepatic regeneration
      mechanism(s) under this milder but clinically more relevant condition. RESULTS:
      Proteins from sham-operated mouse livers and livers regenerating for 24 h after
      50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass
      spectrometry. Compared to sham-operated group, there were totally 87
      differentially expressed proteins (with 50 up-regulated and 37 down-regulated
      ones) identified in the regenerating mouse livers, most of which have not been
      previously related to liver regeneration. Remarkably, over 25 differentially
      expressed proteins were located at mitochondria. Several of the mitochondria
      resident proteins which play important roles in citric acid cycle, oxidative
      phosphorylation and ATP production were found to be down-regulated, consistent
      with the recently-proposed model in which the reduction of ATP content in the
      remnant liver gives rise to early stress signals that contribute to the onset of
      liver regeneration. Pathway analysis revealed a central role of c-Myc in the
      regulation of liver regeneration. CONCLUSIONS: Our study provides novel evidence
      for mitochondria as a pivotal organelle that is connected to liver regeneration,
      and lays the foundation for further studies on key factors and pathways involved
      in liver regeneration following 50% PH, a condition frequently used for partial
      liver transplantation and conservative liver resection.

PMID- 20040085
TI  - 3PD: Rapid design of optimal primers for chromosome conformation capture assays.
AB  - BACKGROUND: Higher eukaryotes control the expression of their genes by mechanisms
      that we are just beginning to understand. A complex layer of control is the
      dynamic spatial organization of the nucleus. RESULTS: We present a bioinformatics
      solution (3PD) to support the experimentalist in detecting long-ranging intra or
      inter chromosomal contacts by Chromosome conformation capture (3C) assays. 3C
      assays take a snapshot of chromosomal contacts by a fixation step and quantify
      them by PCR. Our contribution is to rapidly design an optimal primer set for the
      crucial PCR step. Our primer design reduces the level of experimental error as
      primers are highly similar in terms of physical properties and amplicon length.
      All 3C primers are compatible with multiplex PCR reactions. Primer uniqueness is
      checked genome-wide with a suitable index structure. CONCLUSIONS: In summary, our
      software 3PD facilitates genome-wide primer design for 3C experiments in a matter
      of seconds. Our software is available as a web server at:
      http://www.pristionchus.org/3CPrimerDesign/.

PMID- 20040087
TI  - Intensivists' base specialty of training is associated with variations in
      mortality and practice patterns.
AB  - INTRODUCTION: Current evidence regarding whether the staffing of intensive care
      units (ICUs) with a trained Intensivist benefits patient outcomes is discordant.
      We sought to determine whether, among certified Intensivists, base specialty of
      training could contribute to variation in practice patterns and patient outcomes
      in ICUs. METHODS: The records of all patients who were admitted to one of three
      closed multi-system ICUs within tertiary care centers in the Calgary Health
      Region, Alberta, Canada, during a five year period were retrospectively reviewed.
      Outcomes for patients admitted by Intensivists with base training in General
      Internal Medicine, Pulmonary Medicine, or other eligible base specialties
      (Anesthesia, General Surgery, and Emergency Medicine combined) were compared.
      RESULTS: ICU mortality in the entire cohort (n = 9,808) was 17.2% and in-hospital
      mortality was 32.0%. After controlling for potential confounders, ICU mortality
      (odds ratio (OR): 0.69; 95% confidence interval (CI): 0.52 to 0.94) was
      significantly lower for patients admitted by Intensivists with Pulmonary Medicine
      as a base specialty of training, but not ICU length of stay (LOS) (coefficient:
      0.11; -0.20 to 0.42) or hospital mortality (OR: 0.88; 0.68 to 1.13). There was no
      difference in ICU or hospital mortality or length of stay between the three base
      specialty groups for patients who were admitted and managed by a single
      Intensivist for their entire ICU admission (n = 4,612). However, we identified
      significant variation in practice patterns between the three specialty groups for
      the number of invasive procedures performed and decisions to limit life
      sustaining therapies. CONCLUSIONS: Intensivists' base specialty of training is
      associated with practice pattern variations. This may contribute to differences
      in processes and outcomes of patient care.

PMID- 20040086
TI  - Efficacy and safety of 2-hour urokinase regime in acute pulmonary embolism: a
      randomized controlled trial.
AB  - BACKGROUNDS: Urokinase (UK) 2 200 U/kg.h for 12 hours infusion(UK-12 h)is an ACCP
      recommended regimen in treating acute pulmonary embolism (PE). It is unclear
      whether this dose and time can be reduced further. We compared the efficacy and
      safety of 20, 000 U/kg for 2 hours (UK-2 h) with the UK-12 h regime in selected
      PE patients. METHODS: A randomized trial involving 129 patients was conducted.
      Patients with acute PE were randomly assigned to receive either UK-12 h (n = 70),
      or UK-2 h (n = 59). The efficacy was determined by the improvement of right heart
      dysfunction and perfusion defect at 24 h and 14 d post UK treatment. The bleeding
      incidence, death rate and PE recurrence were also evaluated. RESULTS: Similarly
      significant improvements in right heart dysfunction and lung perfusion defects
      were observed in both groups. Overall bleeding incidents were low in both groups.
      Major bleeding directly associated with UK infusion occurred in one patient in
      the UK-2 h group and one in the UK-12 h group. Mortality rates were low, with one
      reported fatal recurrent in the UK-12 h group and none in the UK-2 h group. When
      the rate of bleeding, death and PE recurrence were compared separately in the
      hemodynamic instability and the massive anatomic obstruction subgroups, no
      significant difference was found. CONCLUSIONS: The UK-2 h regimen exhibits
      similar efficacy and safety as the UK-12 h regimen for acute PE.

PMID- 20040088
TI  - Action Plan to enhance self-management and early detection of exacerbations in
      COPD patients; a multicenter RCT.
AB  - BACKGROUND: Early detection of exacerbations by COPD patients initiating prompt
      interventions has shown to be clinically relevant. Until now, research failed to
      identify the effectiveness of a written individualized Action Plan (AP) to
      achieve this. METHODS/DESIGN: The current multicenter, single-blind RCT with a
      follow-up period of 6 months, evaluates the hypothesis that individualized AP's
      reduce exacerbation recovery time. Patients are included from regular respiratory
      nurse clinics and allocated to either usual care or the AP intervention. The AP
      provides individualized treatment prescriptions (pharmaceutical and non
      pharmaceutical) related to a color coded symptom status (reinforcement at 1 and 4
      months). Although usually not possible in self-management trials, we ensured
      blinding of patients, using a modified informed consent procedure in which
      patients give consent to postponed information. Exacerbations in both study arms
      are defined using the Anthonisen symptom diary-card algorithm. The Clinical COPD
      Questionnaire (CCQ) is assessed every 3-days. CCQ-recovery time of an
      exacerbation is the primary study outcome. Additionally, healthcare utilization,
      anxiety, depression, treatment delay, and self-efficacy are assessed at baseline
      and 6 months. We aim at including 245 COPD patients from 7 hospitals and 5
      general practices to capture the a-priori sample size of at least 73
      exacerbations per study arm. DISCUSSION: This RCT identifies if an AP is an
      effective component of self-management in patients with COPD and clearly
      differentiates from existing studies in its design, outcome measures and
      generalizability of the results considering that the study is carried out in
      multiple sites including general practices.

PMID- 20040089
TI  - A reproducible brain tumour model established from human glioblastoma biopsies.
AB  - BACKGROUND: Establishing clinically relevant animal models of glioblastoma
      multiforme (GBM) remains a challenge, and many commonly used cell line-based
      models do not recapitulate the invasive growth patterns of patient GBMs.
      Previously, we have reported the formation of highly invasive tumour xenografts
      in nude rats from human GBMs. However, implementing tumour models based on
      primary tissue requires that these models can be sufficiently standardised with
      consistently high take rates. METHODS: In this work, we collected data on growth
      kinetics from a material of 29 biopsies xenografted in nude rats, and
      characterised this model with an emphasis on neuropathological and radiological
      features. RESULTS: The tumour take rate for xenografted GBM biopsies were 96% and
      remained close to 100% at subsequent passages in vivo, whereas only one of four
      lower grade tumours engrafted. Average time from transplantation to the onset of
      symptoms was 125 days +/- 11.5 SEM. Histologically, the primary xenografts
      recapitulated the invasive features of the parent tumours while endothelial cell
      proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the
      tumours became more vascular with necrotic areas, but also appeared more
      circumscribed. MRI typically revealed changes related to tumour growth, several
      months prior to the onset of symptoms. CONCLUSIONS: In vivo passaging of patient
      GBM biopsies produced tumours representative of the patient tumours, with high
      take rates and a reproducible disease course. The model provides combinations of
      angiogenic and invasive phenotypes and represents a good alternative to in vitro
      propagated cell lines for dissecting mechanisms of brain tumour progression.

PMID- 20040090
TI  - Tuberculosis and HIV co-infection: its impact on quality of life.
AB  - BACKGROUND: Very little is known about the quality of life of tuberculosis (TB)
      and HIV co-infected patients. In this study in Ethiopia, we compared the quality
      of life HIV positive patients with and without TB. METHODS: A cross sectional
      study was conducted from February to April, 2009 in selected hospitals in Oromiya
      Regional state, Ethiopia. The study population consisted of 467 HIV patients and
      124 TB/HIV co-infected patients. Data on quality of life was collected by trained
      nurses through face to face interviews using the short Amharic version of the
      World Health Organization Quality of Life Instrument for HIV clients (WHOQOL
      HIV). Depression was assessed using a validated version of the Kessler scale.
      Data was collected by trained nurses and analyzed using SPSS 15.0 statistical
      software. RESULTS: TB/HIV co-infected patients had a lower quality of life in all
      domains as compared to HIV infected patients without active TB. Depression,
      having a source of income and family support were strongly associated with most
      of the Quality of life domains. In co-infected patients, individuals who had
      depression were 8.8 times more likely to have poor physical health as compared to
      individuals who had no depression, OR = 8.8(95%CI: 3.2, 23). Self-stigma was
      associated with a poor quality of life in the psychological domain. CONCLUSION:
      The TB control program should design strategies to improve the quality of life of
      TB/HIV co-infected patients. Depression and self-stigma should be targeted for
      intervention to improve the quality of life of patients.

PMID- 20040091
TI  - Doubtful outcome of the validation of the Rome II questionnaire: validation of a
      symptom based diagnostic tool.
AB  - BACKGROUND: Questionnaires are used in research and clinical practice. For
      gastrointestinal complaints the Rome II questionnaire is internationally known
      but not validated. The aim of this study was to validate a printed and a
      computerized version of Rome II, translated into Swedish. Results from various
      analyses are reported. METHODS: Volunteers from a population based colonoscopy
      study were included (n = 1011), together with patients seeking general practice
      (n = 45) and patients visiting a gastrointestinal specialists' clinic (n = 67).
      The questionnaire consists of 38 questions concerning gastrointestinal symptoms
      and complaints. Diagnoses are made after a special code. Our validation included
      analyses of the translation, feasibility, predictability, reproducibility and
      reliability. Kappa values and overall agreement were measured. The factor
      structures were confirmed using a principal component analysis and Cronbach's
      alpha was used to test the internal consistency. RESULTS AND DISCUSSION:
      Translation and back translation showed good agreement. The questionnaire was
      easy to understand and use. The reproducibility test showed kappa values of 0.60
      for GERS, 0.52 for FD, and 0.47 for IBS. Kappa values and overall agreement for
      the predictability when the diagnoses by the questionnaire were compared to the
      diagnoses by the clinician were 0.26 and 90% for GERS, 0.18 and 85% for FD, and
      0.49 and 86% for IBS. Corresponding figures for the agreement between the printed
      and the digital version were 0.50 and 92% for GERS, 0.64 and 95% for FD, and 0.76
      and 95% for IBS. Cronbach's alpha coefficient for GERS was 0.75 with a span per
      item of 0.71 to 0.76. For FD the figures were 0.68 and 0.54 to 0.70 and for IBS
      0.61 and 0.56 to 0.66. The Rome II questionnaire has never been thoroughly
      validated before even if diagnoses made by the Rome criteria have been compared
      to diagnoses made in clinical practice. CONCLUSION: The accuracy of the Swedish
      version of the Rome II is of doubtful value for clinical practice and research.
      The results for reproducibility and reliability were acceptable but the outcome
      of the predictability test was poor with IBS as an exception. The agreement
      between the digital and the paper questionnaire was good.

PMID- 20040092
TI  - Gene expression profiling supports the hypothesis that human ovarian surface
      epithelia are multipotent and capable of serving as ovarian cancer initiating
      cells.
AB  - BACKGROUND: Accumulating evidence suggests that somatic stem cells undergo
      mutagenic transformation into cancer initiating cells. The serous subtype of
      ovarian adenocarcinoma in humans has been hypothesized to arise from at least two
      possible classes of progenitor cells: the ovarian surface epithelia (OSE) and/or
      an as yet undefined class of progenitor cells residing in the distal end of the
      fallopian tube. METHODS: Comparative gene expression profiling analyses were
      carried out on OSE removed from the surface of normal human ovaries and ovarian
      cancer epithelial cells (CEPI) isolated by laser capture micro-dissection (LCM)
      from human serous papillary ovarian adenocarcinomas. The results of the gene
      expression analyses were randomly confirmed in paraffin embedded tissues from
      ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using
      immunohistochemistry. Differentially expressed genes were analyzed using gene
      ontology, molecular pathway, and gene set enrichment analysis algorithms.
      RESULTS: Consistent with multipotent capacity, genes in pathways previously
      associated with adult stem cell maintenance are highly expressed in ovarian
      surface epithelia and are not expressed or expressed at very low levels in serous
      ovarian adenocarcinoma. Among the over 2000 genes that are significantly
      differentially expressed, a number of pathways and novel pathway interactions are
      identified that may contribute to ovarian adenocarcinoma development.
      CONCLUSIONS: Our results are consistent with the hypothesis that human ovarian
      surface epithelia are multipotent and capable of serving as the origin of ovarian
      adenocarcinoma. While our findings do not rule out the possibility that ovarian
      cancers may also arise from other sources, they are inconsistent with claims that
      ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating
      cells.

PMID- 20040093
TI  - Prediction of breast self-examination in a sample of Iranian women: an
      application of the Health Belief Model.
AB  - BACKGROUND: Iranian women, many of whom live in small cities, have limited access
      to mammography and clinical breast examinations. Thus, breast self examination
      (BSE) becomes an important and necessary approach to detecting this disease in
      its early stages in order to limit its resultant morbidity and mortality. This
      study examined constructs arising from the Health Belief Model as predictors of
      breast self examination behavior in a sample of women living in Bandar Abbas,
      Iran. METHODS: This study was conducted in eight health centers located in Bandar
      Abbas, Iran. The sample consisted of 240 eligible women who were selected from
      referrals to the centers. The inclusion criteria were as follows: aged 30 years
      and over; and able to read and write Farsi. Women with breast cancer, who were
      pregnant, or breast feeding, were excluded from the study. Data were collected by
      using a self administered questionnaire which included demographic
      characteristics and Champion's Health Belief Model Scale. This instrument
      measures the concepts of disease susceptibility (3 items), seriousness (6 items),
      benefits (4 items), barriers (8 items) and self-efficacy (10 items). RESULTS: The
      subjects' mean age was 37.2 (SD = 6.1) years. Just under a third of the subjects
      (31.7%) had performed BSE in the past and 7.1% of them performed it at least
      monthly. Perceived benefits and perceived self-efficacy of the women who
      performed BSE were significantly higher compared with women who did not practice
      BSE (p < 0.03). Furthermore, perceived barriers were lower among those who had
      performed BSE (p < 0.001). Logistic regression analysis indicated that women who
      perceived fewer barriers (OR: 0.70, 95% CI: 0.63-0.77, p < 0.001) and had higher
      self-efficacy (OR: 1.08, 95% CI: 1.02-1.13, p = 0.003) were more likely to
      perform BSE (R2 = 0.52). CONCLUSION: Findings from this study indicated that
      perceived barriers and perceived self-efficacy could be predictors of BSE
      behavior among the sample of women. Therefore, BSE training programs that
      emphasize self-efficacy and address perceived barriers are recommended.

PMID- 20040094
TI  - Identification and dynamics of a beneficial mutation in a long-term evolution
      experiment with Escherichia coli.
AB  - BACKGROUND: Twelve populations of E. coli were serially propagated for 20,000
      generations in a glucose-supplemented minimal medium in order to study the
      dynamics of evolution. We sought to find and characterize one of the beneficial
      mutations responsible for the adaptation and other phenotypic changes, including
      increased cell size, in one of these populations. RESULTS: We used transposon
      tagging followed by P1-transduction into the ancestor, screening for increased
      cell size and fitness, co-transduction analysis, and DNA sequencing. We
      identified a 1-bp insertion in the BoxG1 region located upstream of glmUS, an
      operon involved in cell-wall biosynthesis. When transduced into the ancestor,
      this mutation increased competitive fitness by about 5%. This mutation spread
      through its population of origin between 500 and 1500 generations. Mutations in
      this region were not found in the other 11 evolving populations, even after
      20,000 generations. CONCLUSION: The 1-bp insertion in the BoxG1 region near glmUS
      was demonstrably beneficial in the environment in which it arose. The absence of
      similar mutations in the other evolved populations suggests that they substituted
      other mutations that rendered this particular mutation unimportant. These results
      show the unpredictability of adaptive evolution, whereas parallel substitutions
      at other loci in these same populations reveal the predictability.

PMID- 20040095
TI  - Autonomous growth potential of leukemia blast cells is associated with poor
      prognosis in human acute leukemias.
AB  - We have described a severe combined immunodeficiency (SCID) mouse model that
      permits the subcutaneous growth of primary human acute leukemia blast cells into
      a measurable subcutaneous nodule which may be followed by the development of
      disseminated disease. Utilizing the SCID mouse model, we examined the growth
      potential of leukemic blasts from 133 patients with acute leukemia, (67 acute
      lymphoblastic leukemia (ALL) and 66 acute myeloid leukemia (AML)) in the animals
      after subcutaneous inoculation without conditioning treatment. The blasts
      displayed three distinct growth patterns: "aggressive", "indolent", or "no tumor
      growth". Out of 133 leukemias, 45 (33.8%) displayed an aggressive growth pattern,
      14 (10.5%) displayed an indolent growth pattern and 74 (55.6%) did not grow in
      SCID mice. The growth probability of leukemias from relapsed and/or refractory
      disease was nearly 3 fold higher than that from patients with newly diagnosed
      disease. Serial observations found that leukemic blasts from the same individual,
      which did not initiate tumor growth at initial presentation and/or at early
      relapse, may engraft and grow in the later stages of disease, suggesting that the
      ability of leukemia cells for engraftment and proliferation was gradually
      acquired following the process of leukemia progression. Nine autonomous growing
      leukemia cell lines were established in vitro. These displayed an aggressive
      proliferation pattern, suggesting a possible correlation between the capacity of
      human leukemia cells for autonomous proliferation in vitro and an aggressive
      growth potential in SCID mice. In addition, we demonstrated that patients whose
      leukemic blasts displayed an aggressive growth and dissemination pattern in SClD
      mice had a poor clinical outcome in patients with ALL as well as AML. Patients
      whose leukemic blasts grew indolently or whose leukemia cells failed to induce
      growth had a significantly longer DFS and more favorable clinical course.

PMID- 20040096
TI  - Cost analyses of a web-based behavioral intervention to enhance fruit and
      vegetable consumption.
AB  - BACKGROUND: The purpose of this paper is to evaluate costs associated with the
      online intervention trial, Making Effective Nutritional Choices for Cancer
      Prevention (MENU), and to connect the findings to the study outcomes. METHODS:
      Using prospective data collected during the MENU development and implementation
      phases, we estimated overall costs per person, incremental costs for the three
      arms of the MENU intervention, and incremental costs per change in fruit and
      vegetable (F&V) consumption across the studied population. The MENU study was
      conducted in five HMO sites of the Cancer Research Network. The number of
      eligible study participants who were enrolled in the study was 2,540. Recruited
      participants were randomized into (1) an untailored website program, (2) tailored
      website program, or (3) tailored web program plus personalized counseling (HOBI)
      via email. The primary measures for these analyses include the total intervention
      costs, average cost per participant, and the average cost per mean change in
      daily intake of F&V, stratified by study arm. RESULTS: The mean change in F&V
      consumption was greater in both the tailored arm and statistically higher in the
      HOBI arm relative to the untailored arm. The untailored arm achieved +2.34
      servings increase vs. the tailored website arm (+2.68) and the HOBI arm (+2.80)
      servings increase. Total intervention costs for MENU participants who completed
      the 12-month follow-up assessment, by study arm, were estimated to be $197,197 or
      $110 respectively. This translates to $69 per participant in the untailored web
      site intervention, $81 per participant in the tailored website intervention, and
      $184 per participant in the HOBI intervention and a cost per average change in
      F&V consumption to be $35, $27 and $61 respectively. CONCLUSIONS: Providing
      personalized "tailored" messages and additional personalized support via email
      generated an additional $12-$115 per participant, over the untailored web
      program. Incremental increases in F&V consumption associated with the email
      support arm were associated with considerable increases in intervention costs,
      suggesting that the most cost effective arm of the MENU study by servings gained
      was the tailored website.

PMID- 20040097
TI  - Molecular mechanism of regulation of OGG1: tuberin deficiency results in
      cytoplasmic redistribution of transcriptional factor NF-YA.
AB  - The tuberous sclerosis complex (TSC) is caused by defects in one of two tumor
      suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved
      in the pathogenesis of kidney tumors, both angiomyolipomas and renal cell
      carcinomas. On the other hand, mice-deficient in the DNA repair enzyme OGG1
      spontaneously develop adenoma and carcinoma. Downregulation of tuberin results in
      a marked decrease of OGG1 and accumulation of oxidative DNA damage, (8-oxodG) in
      cultured cells. In addition, tuberin haploinsufficiency is associated with the
      loss of OGG1 and accumulation of 8-oxodG in rat kidney tumor. Deficiency in
      tuberin results in decreased OGG1 and NF-YA protein expression and increased 8
      oxodG in kidney tumor from TSC patients. In the current study, molecular
      mechanisms by which tuberin regulates OGG1 were explored. The deficiency of
      tuberin was associated with a significant decrease in NF-YA and loss of OGG1 in
      kidney tumors of Eker rat. Downregulation of tuberin by siRNA resulted in a
      marked decrease in NF-YA and OGG1 protein expression in human renal epithelial
      cells. Localization of NF-YA in wild type and tuberin-deficient cells was
      examined by western blot and immunostaining assays. In wild type cells, NF-YA was
      detected in the nucleus while in tuberin deficient cells in the cyotoplasm.
      Introducing adenovirus-expressing tuberin (Ad-TSC2) into tuberin-deficient cells
      restored the nuclear localization of NF-YA. These data define a novel mechanism
      of regulation of OGG1 through tuberin. This mechanism may be important in the
      pathogenesis of kidney tumors in patients with TSC disease.

PMID- 20040098
TI  - A white-box approach to microarray probe response characterization: the BaFL
      pipeline.
AB  - BACKGROUND: Microarrays depend on appropriate probe design to deliver the promise
      of accurate genome-wide measurement. Probe design, ideally, produces a unique
      probe-target match with homogeneous duplex stability over the complete set of
      probes. Much of microarray pre-processing is concerned with adjusting for non
      ideal probes that do not report target concentration accurately. Cross
      hybridizing probes (non-unique), probe composition and structure, as well as
      platform effects such as instrument limitations, have been shown to affect the
      interpretation of signal. Data cleansing pipelines seldom filter specifically for
      these constraints, relying instead on general statistical tests to remove the
      most variable probes from the samples in a study. This adjusts probes
      contributing to ProbeSet (gene) values in a study-specific manner. We refer to
      the complete set of factors as biologically applied filter levels (BaFL) and have
      assembled an analysis pipeline for managing them consistently. The pipeline and
      associated experiments reported here examine the outcome of comprehensively
      excluding probes affected by known factors on inter-experiment target behavior
      consistency. RESULTS: We present here a 'white box' probe filtering and intensity
      transformation protocol that incorporates currently understood factors affecting
      probe and target interactions; the method has been tested on data from the
      Affymetrix human GeneChip HG-U95Av2, using two independent datasets from studies
      of a complex lung adenocarcinoma phenotype. The protocol incorporates probe
      specific effects from SNPs, cross-hybridization and low heteroduplex affinity, as
      well as effects from scanner sensitivity, sample batches, and includes simple
      statistical tests for identifying unresolved biological factors leading to sample
      variability. Subsequent to filtering for these factors, the consistency and
      reliability of the remaining measurements is shown to be markedly improved.
      CONCLUSIONS: The data cleansing protocol yields reproducible estimates of a given
      probe or ProbeSet's (gene's) relative expression that translates across datasets,
      allowing for credible cross-experiment comparisons. We provide supporting
      evidence for the validity of removing several large classes of probes, and for
      our approaches for removing outlying samples. The resulting expression profiles
      demonstrate consistency across the two independent datasets. Finally, we
      demonstrate that, given an appropriate sampling pool, the method enhances the t
      test's statistical power to discriminate significantly different means over
      sample classes.

PMID- 20040099
TI  - Rapid spread of complex change: a case study in inpatient palliative care.
AB  - BACKGROUND: Based on positive findings from a randomized controlled trial, Kaiser
      Permanente's national executive leadership group set an expectation that all
      Kaiser Permanente and partner hospitals would implement a consultative model of
      interdisciplinary, inpatient-based palliative care (IPC). Within one year, the
      number of IPC consultations program-wide increased almost tenfold from baseline,
      and the number of teams nearly doubled. We report here results from a qualitative
      evaluation of the IPC initiative after a year of implementation; our purpose was
      to understand factors supporting or impeding the rapid and consistent spread of a
      complex program. METHODS: Quality improvement study using a case study design and
      qualitative analysis of in-depth semi-structured interviews with 36 national,
      regional, and local leaders. RESULTS: Compelling evidence of impacts on patient
      satisfaction and quality of care generated 'pull' among adopters, expressed as a
      remarkably high degree of conviction about the value of the model. Broad
      leadership agreement gave rise to sponsorship and support that permeated the
      organization. A robust social network promoted knowledge exchange and built on an
      existing network with a strong interest in palliative care. Resource constraints,
      pre-existing programs of a different model, and ambiguous accountability for
      implementation impeded spread. CONCLUSIONS: A complex, hospital-based,
      interdisciplinary intervention in a large health care organization spread rapidly
      due to a synergy between organizational 'push' strategies and grassroots-level
      pull. The combination of push and pull may be especially important when the
      organizational context or the practice to be spread is complex.

PMID- 20040100
TI  - Methodological limitations of psychosocial interventions in patients with an
      implantable cardioverter-defibrillator (ICD) A systematic review.
AB  - BACKGROUND: Despite the potentially life-saving benefits of the implantable
      cardioverter-defibrillator (ICD), a significant group of patients experiences
      emotional distress after ICD implantation. Different psychosocial interventions
      have been employed to improve this condition, but previous reviews have suggested
      that methodological issues may limit the validity of such interventions. AIM: To
      review the methodology of previously published studies of psychosocial
      interventions in ICD patients, according to CONSORT statement guidelines for non
      pharmacological interventions, and provide recommendations for future research.
      METHODS: We electronically searched the PubMed, PsycInfo and Cochrane databases.
      To be included, studies needed to be published in a peer-reviewed journal between
      1980 and 2008, to involve a human population aged 18+ years and to have an
      experimental design. RESULTS: Twelve studies met the eligibility criteria.
      Samples were generally small. Interventions were very heterogeneous; most studies
      used cognitive behavioural therapy (CBT) and exercise programs either as unique
      interventions or as part of a multi-component program. Overall, studies showed a
      favourable effect on anxiety (6/9) and depression (4/8). CBT appeared to be the
      most effective intervention. There was no effect on the number of shocks and
      arrhythmic events, probably because studies were not powered to detect such an
      effect. Physical functioning improved in the three studies evaluating this
      outcome. Lack of information about the indication for ICD implantation (primary
      vs. secondary prevention), limited or no information regarding use of anti
      arrhythmic (9/12) and psychotropic (10/12) treatment, lack of assessments of
      providers' treatment fidelity (12/12) and patients' adherence to the intervention
      (11/12) were the most common methodological limitations. CONCLUSIONS: Overall,
      this review supports preliminary evidence of a positive effect of psychosocial
      interventions on anxiety and physical functioning in ICD patients. However, these
      initial findings must be interpreted cautiously because of important
      methodological limitations. Future studies should be designed as large RCTs,
      whose design takes into account the specific challenges associated with the
      evaluation of behavioural interventions.

PMID- 20040101
TI  - Production and characterization of recombinant pertactin, fimbriae 2 and fimbriae
      3 from Bordetella pertussis.
AB  - BACKGROUND: Bordetella pertussis is a causative agent of pertussis or whooping
      cough in humans. Pertactin (Prn), fimbriae 2 (Fim2) and fimbriae 3 (Fim3) of B.
      pertussis are important virulence factors and immunogens which have been included
      in some acellular pertussis vaccines. In this present study, we cloned, expressed
      and purified Prn, Fim2 and Fim3, respectively. The immunogenicity and protective
      efficacy of the three recombinant proteins (rPrn, rFim2 and rFim3) were
      investigated in mouse model. RESULTS: Three recombinant proteins with amount of
      12 to 25 mg/L were produced. Compared to the control mice only immunized with
      adjuvant, serum IgG antibody responses were significantly induced in the mice
      immunized with rPrn, rFim2 or rFim3 (P < 0.001 for all three proteins).
      Furthermore, T cell responses characteristic of increased production of IL-2 and
      TNF-alpha (only for rPrn) were elicited in the mice immunized with the three
      proteins (P < 0.05 for all three proteins). Immunization with rPrn, but not with
      rFim2 or rFim3, significantly enhanced clearance of bacteria in the lungs of mice
      after intranasal challenge with B. pertussis (P < 0.05). When tested in a lethal
      intracerebral infection model, certain protection was observed in mice immunized
      with rPrn. CONCLUSIONS: We have developed an efficient method to produce large
      amounts of rPrn, rFim2, and rFim3 from B. pertussis. The three recombinant
      proteins induced both humoral and cellular immune responses in mice. Immunization
      with rPrn also conferred protection against pertussis in mouse infection models.
      Our results indicated that the recombinant proteins still retain their
      immunological properties and highlighted the potential of the recombinant
      proteins for the future development of the B. pertussis vaccines.

PMID- 20040102
TI  - Selection of reference genes for quantitative RT-PCR studies in Rhipicephalus
      (Boophilus) microplus and Rhipicephalus appendiculatus ticks and determination of
      the expression profile of Bm86.
AB  - BACKGROUND: For accurate and reliable gene expression analysis, normalization of
      gene expression data against reference genes is essential. In most studies on
      ticks where (semi-)quantitative RT-PCR is employed, normalization occurs with a
      single reference gene, usually beta-actin, without validation of its presumed
      expression stability. The first goal of this study was to evaluate the expression
      stability of commonly used reference genes in Rhipicephalus appendiculatus and
      Rhipicephalus (Boophilus) microplus ticks. To demonstrate the usefulness of these
      results, an unresolved issue in tick vaccine development was examined. Commercial
      vaccines against R. microplus were developed based on the recombinant antigen
      Bm86, but despite a high degree of sequence homology, these vaccines are not
      effective against R. appendiculatus. In fact, Bm86-based vaccines give better
      protection against some tick species with lower Bm86 sequence homology. One
      possible explanation is the variation in Bm86 expression levels between R.
      microplus and R. appendiculatus. The most stable reference genes were therefore
      used for normalization of the Bm86 expression profile in all life stages of both
      species to examine whether antigen abundance plays a role in Bm86 vaccine
      susceptibility. RESULTS: The transcription levels of nine potential reference
      genes: beta-actin (ACTB), beta-tubulin (BTUB), elongation factor 1alpha (ELF1A),
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH), glutathione S-transferase
      (GST), H3 histone family 3A (H3F3A), cyclophilin (PPIA), ribosomal protein L4
      (RPL4) and TATA box binding protein (TBP) were measured in all life stages of R.
      microplus and R. appendiculatus. ELF1A was found to be the most stable expressed
      gene in both species following analysis by both geNorm and Normfinder software
      applications, GST showed the least stability. The expression profile of Bm86 in
      R. appendiculatus and R. microplus revealed a more continuous Bm86 antigen
      abundance in R. microplus throughout its one-host life cycle compared to the
      three-host tick R. appendiculatus where large variations were observed between
      different life stages. CONCLUSION: Based on these results, ELF1A can be proposed
      as an initial reference gene for normalization of quantitative RT-PCR data in
      whole R. microplus and R. appendiculatus ticks. The observed differences in Bm86
      expression profile between the two species alone can not adequately explain the
      lack of a Bm86 vaccination effect in R. appendiculatus.

PMID- 20040103
TI  - Association of DRD4 uVNTR and TP53 codon 72 polymorphisms with schizophrenia: a
      case-control study.
AB  - BACKGROUND: The tumour supressor gene TP53 is thought to be involved in neural
      apoptosis. The polymorphism at codon 72 in TP53 and the long form variants of the
      upstream variable number of tandem repeats (uVNTR) polymorphism in the dopamine
      D4 receptor (DRD4) gene are reported to confer susceptibility to schizophrenia.
      METHODS: We recruited 934 patients with schizophrenia and 433 healthy
      individuals, and genotyped the locus of the TP53 codon 72 and DRD4 uVNTR
      polymorphisms by combining the polymerase chain reaction-restriction fragment
      length polymorphism method (PCR-RFLP) with direct sequencing. RESULTS: No
      significant differences were found in the frequency of the genotype of the TP53
      codon72 polymorphism between patients with schizophrenia and their controls.
      However, the long form alleles (> or = 5 repeats) of the DRD4 uVNTR polymorphism
      were more frequent in patients with schizophrenia than in controls (p = 0.001).
      Hence, this class of alleles might be a risk factor for enhanced vulnerability to
      schizophrenia (odds ratio = 3.189, 95% confidence interval = 1.535-6.622). In the
      logistic regression analysis, the long form variants of the DRD4 polymorphism did
      predict schizophrenia after the contributions of the age and gender of the
      subjects were included (p = 0.036, OR = 2.319), but the CC and GG genotypes of
      the codon 72 polymorphism of TP53 did not. CONCLUSIONS: The long form variants of
      the uVNTR polymorphism in DRD4 were associated with schizophrenia, in a manner
      that was independent of the TP53 codon 72 polymorphism. In addition, given that
      the genetic effect of the TP53 codon 72 polymorphism on the risk of developing
      schizophrenia was very small, this polymorphism is unlikely to be associated with
      schizophrenia. The roles that other single nucleotide polymorphisms (SNPs) in the
      TP53 gene or in other apoptosis-related genes play in the synaptic dysfunction
      involved in the pathogenesis of schizophrenia should be investigated.

PMID- 20040104
TI  - Molecular characterisation of Vibrio cholerae O1 strains carrying an SXT/R391
      like element from cholera outbreaks in Kenya: 1994-2007.
AB  - BACKGROUND: Over the last decade, cholera outbreaks in parts of Kenya have become
      common. Although a number of recent studies describe the epidemiology of cholera
      in Kenya, there is paucity of information concerning the diversity and occurrence
      of mobile genetic elements in Vibrio cholerae strains implicated in these
      outbreaks. A total of 65 Vibrio cholerae O1 El Tor serotype Inaba isolated
      between 1994 and 2007 from various outbreaks in Kenya were investigated for
      mobile genetic elements including integrons, transposons, the integrating
      conjugative elements (ICEs), conjugative plasmids and for their genotypic
      relatedness. RESULTS: All the strains were haemolytic on 5% sheep blood and
      positive for the Vibrio cholerae El Tor-specific haemolysin toxin gene (hylA) by
      PCR. They all contained strB, sulII, floR and the dfrA1 genes encoding resistance
      to streptomycin, sulfamethoxazole, chloramphenicol and trimethoprim respectively.
      These genes, together with an ICE belonging to the SXT/R391 family were
      transferable to the rifampicin-resistant E. coli C600 en bloc. All the strains
      were negative for integron class 1, 2 and 3 and for transposase gene of
      transposon Tn7 but were positive for integron class 4 and the trpM gene of
      transposon Tn21. No plasmids were isolated from any of the 65 strains. All the
      strains were also positive for all V. cholera El Tor pathogenic genes except the
      NAG- specific heat-stable toxin (st) gene. None of the strains were positive for
      virulence genes associated with the V. cholerae classical biotype. All the
      strains were positive for El Tor-specific CTXphi bacteriophage rstrR repressor
      gene (CTXETPhi) but negative for the Classical, Calcutta, and the Environmental
      repressor types. Pulse Field Gel Electrophoresis (PFGE) showed that regardless of
      the year of isolation, all the strains bearing the SXT element were clonally
      related. CONCLUSIONS: This study demonstrates that the V. cholerae O1 strains
      carrying an SXT/R391-like element implicated in recent cholera outbreaks in Kenya
      has not changed significantly between 1994 and 2007 and are clonally related.

PMID- 20040106
TI  - Geocoding police collision report data from California: a comprehensive approach.
AB  - BACKGROUND: Collision geocoding is the process of assigning geographic
      descriptors, usually latitude and longitude coordinates, to a traffic collision
      record. On California police reports, relative collision location is recorded
      using a highway postmile marker or a street intersection. The objective of this
      study was to create a geocoded database of all police-reported, fatal and severe
      injury collisions in the California Statewide Integrated Traffic Records System
      (SWITRS) for years 1997-2006 for use by public agencies. RESULTS: Geocoding was
      completed with a multi-step process. First, pre-processing was performed using a
      scripting language to clean and standardize street name information. A state
      highway network with postmile values was then created using a custom tool written
      in Visual Basic for Applications (VBA) in ArcGIS software. Custom VBA
      functionality was also used to incorporate the offset direction and distance.
      Intersection and address geocoding was performed using ArcGIS, StreetMap Pro 2003
      digital street network, and Google Earth Pro. A total of 142,007 fatal and severe
      injury collisions were identified in SWITRS. The geocoding match rate was 99.8%
      for postmile-coded collisions and 86% for intersection-coded collisions. The
      overall match rate was 91%. CONCLUSIONS: The availability of geocoded collision
      data will be beneficial to clinicians, researchers, policymakers, and
      practitioners in the fields of traffic safety and public health. Potential uses
      of the data include studies of collision clustering on the highway system,
      examinations of the associations between collision occurrence and a variety of
      variables on environmental and social characteristics, including housing and
      personal demographics, alcohol outlets, schools, and parks. The ability to build
      maps may be useful in research planning and conduct and in the delivery of
      information to both technical and non-technical audiences.

PMID- 20040105
TI  - EBNA3C interacts with Gadd34 and counteracts the unfolded protein response.
AB  - EBNA3C is an EBV-encoded nuclear protein, essential for proliferation of EBV
      infected B-lymphocytes. Using EBNA3C amino acids 365-545 in a yeast two hybrid
      screen, we found an interaction with the Growth Arrest and DNA-damage protein,
      Gadd34. When both proteins are overexpressed, Gadd34 can interact with EBNA3C in
      both nuclear and cytoplasmic compartments. Amino acids 483-610 of Gadd34,
      including the two PP1a interaction, and the HSV-1 ICPgamma34.5 homology domains,
      are required for the interaction. Furthermore, interaction is lost with a mutant
      of EBNA3C (509 DVIEVID 515-->AVIAVIA), that abolishes EBNA3C coactivation ability
      as well as SUMO interaction1. In B-cells, Gadd34, and EBNA3C are present in a
      complex with PP1a using microcystin sepharose affinity purification, Using a
      lymphoblastoid cell line in which EBNA3C protein levels are conditional on
      hydroxytamoxifen, surprisingly, we found that (i) EBNA3C maintains
      phosphorylation of eIF2alpha at serine 51, and (ii) protects against ER stress
      induced activation of the unfolded protein response as measured by XBP1 (u)
      versus XBP1(s) protein expression and N-terminal ATF6 cleavage. In reporter
      assays, overexpression of Gadd34 enhances EBNA3C's ability to co-activate EBNA2
      activation of the LMP1 promoter. Collectively the data suggest that EBNA3C
      interacts with Gadd34, activating the upstream component of the UPR (eIF2alpha
      phosphorylation) while preventing downstream UPR events (XBP1 activation and ATF6
      cleavage).

PMID- 20040107
TI  - Maternal anthropometry and feeding behavior toward preschool children:
      association with childhood body mass index in an observational study of Chilean
      families.
AB  - BACKGROUND: A better understanding of the link between eating behavior and
      maternal feeding practices with childhood and maternal weight status is of great
      interest. OBJECTIVE: To assess the association between childhood anthropometric
      measures with mothers' Body Mass Index (BMI) and their feeding practices toward
      preschool children in Chile. METHODS: 1029 children (504 boys, 4.3 +/- 0.3 years)
      and their mothers were selected from public nurseries located in low income
      neighborhoods in Santiago. Mothers' BMI, children's BMI and waist-to-height
      ratios were registered. Maternal feeding practices towards their children's
      nutritional habits were measured using an adapted version of the Child Feeding
      Questionnaire (CFQ). RESULTS: We found a direct correlation (p < 0.001) between
      children's BMI z-score and their mothers' BMI, both in boys (Spearman rho = 0.26)
      and girls (rho = 0.30). A direct association was also found between children's
      BMI z-score with scores of the subscale "concern for child's weight" (Spearman
      rho = 0.26 in boys and rho = 0.37 in girls; p < 0.001) and "food restriction"
      (rho = 0.19 in boys and rho = 0.27 in girls; p < 0.001). A reverse significant
      association was found between children's BMI z-score with scores of "pressure to
      eat" (rho = -0.30 in boys and rho = -0.36 in girls; p < 0.001). Analyses of the
      combined categories of childhood obesity and/or maternal obesity showed an
      important influence of children's weight status on CFQ scores. CONCLUSION:
      Mothers' BMI and children's BMI z-scores are highly correlated. We found
      significant associations between mothers' behaviour subscales and children's BMI
      z-score. It is not possible to establish a causal link between mother's CFQ
      scores and children's nutritional status, given the cross-sectional nature of
      this study and the bidirectional influences that exist between mothers and their
      children.

PMID- 20040108
TI  - Glycosylation-mediated phenylpropanoid partitioning in Populus tremuloides cell
      cultures.
AB  - BACKGROUND: Phenylpropanoid-derived phenolic glycosides (PGs) and condensed
      tannins (CTs) comprise large, multi-purpose non-structural carbon sinks in
      Populus. A negative correlation between PG and CT concentrations has been
      observed in several studies. However, the molecular mechanism underlying the
      relationship is not known. RESULTS: Populus cell cultures produce CTs but not PGs
      under normal conditions. Feeding salicyl alcohol resulted in accumulation of
      salicins, the simplest PG, in the cells, but not higher-order PGs. Salicin
      accrual reflected the stimulation of a glycosylation response which altered a
      number of metabolic activities. We utilized this suspension cell feeding system
      as a model for analyzing the possible role of glycosylation in regulating the
      metabolic competition between PG formation, CT synthesis and growth. Cells
      accumulated salicins in a dose-dependent manner following salicyl alcohol
      feeding. Higher feeding levels led to a decrease in cellular CT concentrations
      (at 5 or 10 mM), and a negative effect on cell growth (at 10 mM). The competition
      between salicin and CT formation was reciprocal, and depended on the metabolic
      status of the cells. We analyzed gene expression changes between controls and
      cells fed with 5 mM salicyl alcohol for 48 hr, a time point when salicin
      accumulation was near maximum and CT synthesis was reduced, with no effect on
      growth. Several stress-responsive genes were up-regulated, suggestive of a
      general stress response in the fed cells. Salicyl alcohol feeding also induced
      expression of genes associated with sucrose catabolism, glycolysis and the Krebs
      cycle. Transcript levels of phenylalanine ammonia lyase and most of the flavonoid
      pathway genes were reduced, consistent with down-regulated CT synthesis.
      CONCLUSIONS: Exogenous salicyl alcohol was readily glycosylated in Populus cell
      cultures, a process that altered sugar utilization and phenolic partitioning in
      the cells. Using this system, we identified candidate genes for
      glycosyltransferases that may mediate the glycosylation, and for transporters
      that mediate the subcellular compartmentalization of sugars and phenolic
      glycosides. The suspension cells appear to represent a facile system for
      dissecting the regulation of phenolic carbon partitioning, and in turn, its
      effects on growth in Populus.

PMID- 20040109
TI  - A bi-dimensional genome scan for prolificacy traits in pigs shows the existence
      of multiple epistatic QTL.
AB  - BACKGROUND: Prolificacy is the most important trait influencing the reproductive
      efficiency of pig production systems. The low heritability and sex-limited
      expression of prolificacy have hindered to some extent the improvement of this
      trait through artificial selection. Moreover, the relative contributions of
      additive, dominant and epistatic QTL to the genetic variance of pig prolificacy
      remain to be defined. In this work, we have undertaken this issue by performing
      one-dimensional and bi-dimensional genome scans for number of piglets born alive
      (NBA) and total number of piglets born (TNB) in a three generation Iberian by
      Meishan F(2) intercross. RESULTS: The one-dimensional genome scan for NBA and TNB
      revealed the existence of two genome-wide highly significant QTL located on SSC13
      (P < 0.001) and SSC17 (P < 0.01) with effects on both traits. This relative
      paucity of significant results contrasted very strongly with the wide array of
      highly significant epistatic QTL that emerged in the bi-dimensional genome-wide
      scan analysis. As much as 18 epistatic QTL were found for NBA (four at P < 0.01
      and five at P < 0.05) and TNB (three at P < 0.01 and six at P < 0.05),
      respectively. These epistatic QTL were distributed in multiple genomic regions,
      which covered 13 of the 18 pig autosomes, and they had small individual effects
      that ranged between 3 to 4% of the phenotypic variance. Different patterns of
      interactions (a x a, a x d, d x a and d x d) were found amongst the epistatic QTL
      pairs identified in the current work. CONCLUSIONS: The complex inheritance of
      prolificacy traits in pigs has been evidenced by identifying multiple additive
      (SSC13 and SSC17), dominant and epistatic QTL in an Iberian x Meishan F(2)
      intercross. Our results demonstrate that a significant fraction of the phenotypic
      variance of swine prolificacy traits can be attributed to first-order gene-by
      gene interactions emphasizing that the phenotypic effects of alleles might be
      strongly modulated by the genetic background where they segregate.

PMID- 20040110
TI  - Support for a tax increase to provide unrestricted access to an Alzheimer's
      disease medication: a survey of the general public in Canada.
AB  - BACKGROUND: Public drug insurance plans provide limited reimbursement for
      Alzheimer's disease (AD) medications in many jurisdictions, including Canada and
      the United Kingdom. This study was conducted to assess Canadians' level of
      support for an increase in annual personal income taxes to fund a public program
      of unrestricted access to AD medications. METHODS: A telephone survey was
      administered to a national sample of 500 adult Canadians. The survey contained
      four scenarios describing a hypothetical, new AD medication. Descriptions varied
      across scenarios: the medication was alternatively described as being capable of
      treating the symptoms of cognitive decline or of halting the progression of
      cognitive decline, with either no probability of adverse effects or a 30%
      probability of primarily gastrointestinal adverse effects. After each scenario,
      participants were asked whether they would support a tax increase to provide
      unrestricted access to the drug. Participants who responded affirmatively were
      asked whether they would pay an additional $75, $150, or $225 per annum in taxes.
      Multivariable logistic regression analysis was conducted to examine the
      determinants of support for a tax increase. RESULTS: Eighty percent of
      participants supported a tax increase for at least one scenario. Support was
      highest (67%) for the most favourable scenario (halt progression - no adverse
      effects) and lowest (49%) for the least favourable scenario (symptom treatment -
      30% chance of adverse effects). The odds of supporting a tax increase under at
      least one scenario were approximately 55% less for participants who attached
      higher ratings to their health state under the assumption that they had moderate
      AD and almost five times greater if participants thought family members or
      friends would somewhat or strongly approve of their decision to support a tax
      increase. A majority of participants would pay an additional $150 per annum in
      taxes, regardless of scenario. Less than 50% would pay $225. CONCLUSIONS: Four
      out of five persons in a sample of adult Canadians reported they would support a
      tax increase to fund unrestricted access to a hypothetical, new AD medication.
      These results signal a willingness to pay for at least some relaxation of
      reimbursement restrictions on AD medications.

PMID- 20040111
TI  - Ocular changes in primary hypothyroidism.
AB  - BACKGROUND: To determine the ocular changes related to hypothyrodism in newly
      diagnosed patients without orbitopathy. FINDINGS: Thirty-three patients diagnosed
      to have primary overt hypothyroidism were enrolled in the study. All subjects
      were assigned to underwent central corneal thickness (CCT), anterior chamber
      volume, depth and angle measurements with the Scheimpflug camera (Pentacam,
      Oculus) and cup to disc ratio (C/D), mean retinal thickness and mean retinal
      nerve fiber layer (RNFL) thickness measurements with optical coherence tomography
      (OCT) in addition to ophthalmological examination preceeding the replacement
      therapy and at the 1(st), 3(rd )and 6(th )months of treatment. The mean age of
      the patients included in the study were 40.58 +/- 1.32 years. The thyroid hormone
      levels return to normal levels in all patients during the follow-up period,
      however the mean intraocular pressure (IOP) revealed no significant change. The
      mean CCT was 538.05 +/- 3.85 mu initially and demonstrated no statistically
      significant change as the anterior chamber volume, depth and angle measurements
      did. The mean C/D ratio was 0.29 +/- 0.03 and the mean retinal thickness was
      255.83 +/- 19.49 mu initially and the treatment did not give rise to any
      significant change. The mean RNFL thickness was also stable during the control
      visits, so no statistically significant change was encountered. CONCLUSIONS:
      Neither hypothyroidism, nor its replacement therapy gave rise to any change of
      IOP, CCT, anterior chamber parameters, RNFL, retinal thickness and C/D ratio.

PMID- 20040112
TI  - Temporal and spatial patterns of bovine Escherichia coli O157 prevalence and
      comparison of temporal changes in the patterns of phage types associated with
      bovine shedding and human E. coli O157 cases in Scotland between 1998-2000 and
      2002-2004.
AB  - BACKGROUND: Escherichia coli O157 is an important cause of acute diarrhoea,
      haemorrhagic colitis and, especially in children, haemolytic uraemic syndrome
      (HUS). Incidence rates for human E. coli O157 infection in Scotland are higher
      than most other United Kingdom, European and North American countries. Cattle are
      considered the main reservoir for E. coli O157. Significant associations between
      livestock related exposures and human infection have been identified in a number
      of studies. RESULTS: Animal Studies: There were no statistically significant
      differences (P = 0.831) in the mean farm-level prevalence between the two studies
      (SEERAD: 0.218 (95%CI: 0.141-0.32); IPRAVE: 0.205 (95%CI: 0.135-0.296)). However,
      the mean pat-level prevalence decreased from 0.089 (95%CI: 0.075-0.105) to 0.040
      (95%CI: 0.028-0.053) between the SEERAD and IPRAVE studies respectively (P <
      0.001). Highly significant (P < 0.001) reductions in mean pat-level prevalence
      were also observed in the spring, in the North East and Central Scotland, and in
      the shedding of phage type (PT) 21/28. Human Cases: Contrasting the same time
      periods, there was a decline in the overall comparative annual reported incidence
      of human cases as well as in all the major PT groups except 'Other' PTs. For both
      cattle and humans, the predominant phage type between 1998 and 2004 was PT21/28
      comprising over 50% of the positive cattle isolates and reported human cases
      respectively. The proportion of PT32, however, was represented by few (<5%) of
      reported human cases despite comprising over 10% of cattle isolates. Across the
      two studies there were differences in the proportion of PTs 21/28, 32 and 'Other'
      PTs in both cattle isolates and reported human cases; however, only differences
      in the cattle isolates were statistically significant (P = 0.002). CONCLUSION:
      There was no significant decrease in the mean farm-level prevalence of E. coli
      O157 between 1998 and 2004 in Scotland, despite significant declines in mean pat
      level prevalence. Although there were declines in the number of human cases
      between the two study periods, there is no statistically significant evidence
      that the overall rate (per 100,000 population) of human E. coli O157 infections
      in Scotland over the last 10 years has altered. Comparable patterns in the
      distribution of PTs 21/28 and 32 between cattle and humans support a hypothesized
      link between the bovine reservoir and human infections. This emphasizes the need
      to apply and improve methods to reduce bovine shedding of E. coli O157 in
      Scotland where rates appear higher in both cattle and human populations, than in
      other countries.

PMID- 20040114
TI  - HIV-1 subtype and viral tropism determination for evaluating antiretroviral
      therapy options: an analysis of archived Kenyan blood samples.
AB  - BACKGROUND: Infection with HIV-1 is characterized by genetic diversity such that
      specific viral subtypes are predominant in specific geographical areas. The
      genetic variation in HIV-1 pol and env genes is responsible for rapid development
      of resistance to current drugs. This variation has influenced disease progression
      among the infected and necessitated the search for alternative drugs with novel
      targets. Though successfully used in developed countries, these novel drugs are
      still limited in resource-poor countries. The aim of this study was to determine
      HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among
      Kenyan patients prior to widespread use of antiretroviral drugs. METHODS: Remnant
      blood samples from consenting sexually transmitted infection (STI) patients in
      Nairobi were collected between February and May 2001 and stored. Polymerase chain
      reaction and cloning of portions of HIV-1 gag, pol and env genes was carried out
      followed by automated DNA sequencing. RESULTS: Twenty HIV-1 positive samples
      (from 11 females and 9 males) were analyzed. The average age of males (32.5
      years) and females (26.5 years) was significantly different (p value < 0.0001).
      Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes:
      12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant
      showing different subtypes in the three regions. Of 19 samples checked for co
      receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while
      three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4
      variants being minor population. CONCLUSION: HIV-1 subtype A accounted for
      majority of the infections. Though perceived to be a high risk population, the
      prevalence of recombination in this sample was low with no dual infections
      detected. Genotypic co-receptor analysis showed that most patients harbored
      viruses that are predicted to use CCR5.

PMID- 20040116
TI  - Effects of hydrogen sulfide on inflammation in caerulein-induced acute
      pancreatitis.
AB  - BACKGROUND: Hydrogen sulfide (H(2)S), a gaseous mediator plays an important role
      in a wide range of physiological and pathological processes. H(2)S has been
      extensively studied for its various roles in cardiovascular and neurological
      disorders. However, the role of H(2)S in inflammation is still controversial. The
      current study was aimed to investigate the therapeutic potential of sodium
      hydrosulfide (NaHS), an H(2)S donor in in vivo model of acute pancreatitis in
      mice. METHODS: Acute pancreatitis was induced in mice by hourly caerulein
      injections (50 mug/kg) for 10 hours. Mice were treated with different dosages of
      NaHS (5 mg/kg, 10 mg/kg or 15 mg/kg) or with vehicle, distilled water (DW). NaHS
      or DW was administered 1 h before induction of pancreatitis. Mice were sacrificed
      1 h after the last caerulein injection. Blood, pancreas and lung tissues were
      collected and were processed to measure the plasma amylase, myeloperoxidase (MPO)
      activities in pancreas and lung and chemokines and adhesion molecules in pancreas
      and lung. RESULTS: It was revealed that significant reduction of inflammation,
      both in pancreas and lung was associated with NaHS 10 mg/kg. Further the anti
      inflammatory effects of NaHS 10 mg/kg were associated with reduction of
      pancreatic and pulmonary inflammatory chemokines and adhesion molecules. NaHS 5
      mg/kg did not cause significant improvement on inflammation in pancreas and
      associated lung injury and NaHS 15 mg/kg did not further enhance the beneficial
      effects seen with NaHS 10 mg/kg. CONCLUSION: In conclusion, these data provide
      evidence for anti-inflammatory effects of H(2)S based on its dosage used.

PMID- 20040115
TI  - Genome-wide loss-of-function analysis of deubiquitylating enzymes for zebrafish
      development.
AB  - BACKGROUND: Deconjugation of ubiquitin and/or ubiquitin-like modified protein
      substrates is essential to modulate protein-protein interactions and, thus,
      signaling processes in cells. Although deubiquitylating (deubiquitinating)
      enzymes (DUBs) play a key role in this process, however, their function and
      regulation remain insufficiently understood. The "loss-of-function" phenotype
      studies can provide important information to elucidate the gene function, and
      zebrafish is an excellent model for this goal. RESULTS: From an in silico genome
      wide search, we found more than 90 putative DUBs encoded in the zebrafish genome
      belonging to six different subclasses. Out of them, 85 from five classical
      subclasses have been tested with morpholino (MO) knockdown experiments and 57 of
      them were found to be important in early development of zebrafish. These DUB
      morphants resulted in a complex and pleiotropic phenotype that, regardless of
      gene target, always affected the notochord. Based on the huC neuronal marker
      expression, we grouped them into five sets (groups I to V). Group I DUBs (otud7b,
      uchl3 and bap1) appear to be involved in the Notch signaling pathway based on the
      neuronal hyperplasia, while group IV DUBs (otud4, usp5, usp15 and usp25) play a
      critical role in dorsoventral patterning through the BMP pathway. CONCLUSION: We
      have identified an exhaustive list of genes in the zebrafish genome belonging to
      the five established classes of DUBs. Additionally, we performed the
      corresponding MO knockdown experiments in zebrafish as well as functional studies
      for a subset of the predicted DUB genes. The screen results in this work will
      stimulate functional follow-up studies of potential DUB genes using the zebrafish
      model system.

PMID- 20040113
TI  - Tuning microbial hosts for membrane protein production.
AB  - The last four years have brought exciting progress in membrane protein research.
      Finally those many efforts that have been put into expression of eukaryotic
      membrane proteins are coming to fruition and enable to solve an ever-growing
      number of high resolution structures. In the past, many skilful optimization
      steps were required to achieve sufficient expression of functional membrane
      proteins. Optimization was performed individually for every membrane protein, but
      provided insight about commonly encountered bottlenecks and, more importantly,
      general guidelines how to alleviate cellular limitations during microbial
      membrane protein expression. Lately, system-wide analyses are emerging as
      powerful means to decipher cellular bottlenecks during heterologous protein
      production and their use in microbial membrane protein expression has grown in
      popularity during the past months.This review covers the most prominent solutions
      and pitfalls in expression of eukaryotic membrane proteins using microbial hosts
      (prokaryotes, yeasts), highlights skilful applications of our basic understanding
      to improve membrane protein production. Omics technologies provide new concepts
      to engineer microbial hosts for membrane protein production.

PMID- 20040117
TI  - Effect of hyperlipidemia on the expression of circadian genes in apolipoprotein E
      knock-out atherosclerotic mice.
AB  - BACKGROUND: Circadian patterns of cardiovascular vulnerability were well
      characterized, with a peak incidence of acute myocardial infarction and stroke
      secondary to atherosclerosis in the morning, which showed the circadian clock may
      take part in the pathological process of atherosclerosis induced by
      hyperlipidemia. Hence, the effect of hyperlipidemia on the expression of
      circadian genes was investigated in atherosclerotic mouse model. RESULTS: In apoE
      /-mice on regular chow or high-fat diet, an atherosclerotic mouse model induced
      by heperlipidemia, we found that the peak concentration of serum lipids was
      showed four or eight hours later in apoE-/- mice, compared to C57BL/6J mice.
      During the artificial light period, a reduce in circulating level of serum lipids
      corresponded with the observed increase of the expression levels of some the
      transcription factors involved in lipid metabolism, such as PPARalpha and
      RXRalpha. Meanwhile, the expression of circadian genes was changed following with
      amplitude reduced or the peak mRNA level delayed. CONCLUSIONS: Our studies
      indicated that heperlipidemia altered both the rhythmicity and expression of
      circadian genes. Diet-induced circadian disruption may affect the process of
      atherosclerosis and some acute cardiovascular disease.

PMID- 20040118
TI  - A novel scoring system for prognostic prediction in d
      galactosamine/lipopolysaccharide-induced fulminant hepatic failure BALB/c mice.
AB  - BACKGROUND: It is frequently important to identify the prognosis of fulminant
      hepatic failure (FHF) patients as this will influence patient management and
      candidacy for liver transplantation. Therefore, a novel scoring system based on
      metabonomics combining with multivariate logistic regression was developed to
      predict the prognosis of FHF mouse model. METHODS: BALB/c mice were used to
      construct FHF model. Parts of plasma were collected at 4, 5, and 6-h time points
      after treatment, respectively, and detected using gas chromatography/time-of
      flight mass spectrometry (GC/TOFMS). The acquired data were processed using
      partial least square discriminant analysis (PLS-DA). The metabolic markers
      identified were used to construct a scoring system by multivariate regression
      analysis. RESULTS: 28 mice of survival group and 28 of dead group were randomly
      selected and analyzed. PLS regression analysis showed that both the PLS models of
      5 h and 6 h after d-galactosamine/lipopolysaccharide treatment demonstrated good
      performances. Loadings plot suggested that phosphate, beta-hydroxybutyrate (HB),
      urea, glucose and lactate concentrations in plasma had the highest weightings on
      the clustering differences at the three time points. By the multivariate logistic
      regression analysis, the death/survival index (DSI) was constructed based on
      relative concentrations of HB, urea and phosphate. It provided general accurate
      rate of prediction of 93.3% in the independent samples. CONCLUSIONS: The novel
      scoring system based on metabonomics combining with multivariate logistic
      regression is accurate in predicting the prognosis of FHF mouse model and may be
      referred in clinical practice as a more useful prognostic tool with other
      available information.

PMID- 20040119
TI  - Aminoguanidine inhibits aortic hydrogen peroxide production, VSMC NOX activity
      and hypercontractility in diabetic mice.
AB  - BACKGROUND: Dysfunctionally uncoupled endothelial nitric oxide synthase (eNOS) is
      involved in producing reactive oxygen species (ROS) in the diabetic endothelium.
      The present study investigated whether anti-diabetes drug Aminoguanidine (AG) has
      any effect on eNOS function and vascular oxidant stress. METHODS AND RESULTS:
      Blood glucose levels were increased to 452.0 +/- 15.1 mg/dl in STZ-treated male
      C57BL/6J mice (148.4 +/- 3.2 mg/dl in untreated controls). Aortic productions of
      NO* and O(2)*- were measured specifically and sensitively using electron spin
      resonance. Diabetic mice had a marked increase in aortic O(2)*- production.
      Aortic hydrogen peroxide (H(2)O(2)) production was also increased in diabetic
      aortas and significantly attenuated by AG. AG however had only a marginal effect
      in reducing aortic O(2)*- production, which corresponded to a minimal effect in
      improving aortic nitric oxide (NO*) bioavailability. The endothelium-dependent
      vasodilatation however was modestly but significantly improved by AG, likely
      consequent to AG-induced reduction in hyper-contractility. NAD(P)H oxidase (NOX)
      dependent O(2)*- production was completely attenuated by AG in endothelium
      denuded diabetic aortas. CONCLUSION: In summary, despite that AG is not an
      effective eNOS recoupling agent presumably consequent to its ineffectiveness in
      preventing endothelial NOX activation, it is inhibitory of aortic H(2)O(2)
      production, VSMC NOX activity, and hypercontractility in diabetes.

PMID- 20040121
TI  - Respiratory care controversies II.

PMID- 20040120
TI  - Physical activity monitoring in obese people in the real life environment.
AB  - BACKGROUND: Obesity is a major problem especially in western countries and
      several studies underline the importance of physical activity to enhance diet.
      Currently there is increasing interest in instruments for monitoring daily
      physical activity. The purpose of this pilot study was to appraise the
      qualitative and quantitative differences in physical activities and gait analysis
      parameters in control and obese subjects by means of an innovative tool for the
      monitoring of physical activity. METHODS: Twenty-six obese patients, 16 women and
      10 men, aged 22 to 69 years with Body Mass Index (BMI) between 30 and 51.4 kg/m2,
      were compared with 15 control subjects, 4 men and 11 women, aged 24 to 69 with
      BMI between 18 and 25 kg/m2 during daily physical activities. The IDEEA device
      (Minisun, Fresno, CA), based on a wearable system of biaxial accelerometers and
      able to continuously record the physical activities and energy expenditure of a
      subject in time was used. Time spent in different physical activities such as
      standing, sitting, walking, lying, reclining, stepping, energy expenditure and
      gait parameters (velocity, stance duration, etc) were measured during a 24-hours
      period. RESULTS: A trend toward a reduced number of steps was present, associated
      to reduced speed, reduced cadence and reduced rate of single and double limb
      support (SLS/DLS). Moreover, obese people spent significant less time stepping,
      less time lying and more time in a sitting or reclined position during the night.
      The energy expenditure during a 24-hours period was higher in the obese compared
      to controls. CONCLUSIONS: The study provided objective parameters to
      differentiate the daily motor activity of obese subjects with respect to
      controls, even a larger population is required to confirm these findings. The
      device used can be of support in programming educational activities for life
      style modification in obese people as well as for monitoring the results of
      various kinds of intervention in these patients concerning weight and physical
      performance.

PMID- 20040122
TI  - Is there a role for screening spirometry?
AB  - In obstructive lung disease, the characteristic change in spirometry is a
      reduction in the forced expiratory volume in the first second (FEV(1)) with
      respect to the vital capacity. Moreover, the severity of the obstruction can be
      graded by referencing spirometric measurements to age, sex, and height predicted
      normal values. Spirometry, however, should be considered a medical test, and not
      simply a vital sign that anyone can perform. Indeed, both technical issues and
      tester skills can profoundly affect the results and interpretations. Properly
      done spirometry can guide therapies and predict outcomes, but using spirometry to
      screen for obstructive lung disease in asymptomatic populations can be
      problematic, and the effects of screening spirometry on outcomes have yet to be
      determined. The value of spirometry is increased when it is of good quality, is
      interpreted properly, and is used in high-risk populations as a case-finding
      rather than a screening tool.

PMID- 20040123
TI  - Are corticosteroids useful in late-stage acute respiratory distress syndrome?
AB  - The acute respiratory distress syndrome (ARDS) is characterized by intense
      inflammation and alveolar-capillary disruption that can progress to a state of
      unresolving inflammation and disordered fibrosis, referred to as
      fibroproliferative, late-stage, or persistent ARDS. These pathophysiologic
      features may be responsive to corticosteroids, but early high-dose, short
      duration therapy was proven ineffective. More recently, several small and one
      moderate-size multicenter randomized controlled trial (RCT) investigated low-to
      moderate-dose prolonged corticosteroid treatment. The RCT and meta-analysis
      consistently demonstrated improved oxygenation and shorter duration of mechanical
      ventilation with methylprednisolone. The largest RCT also revealed less pneumonia
      and shock, and shorter intensive care unit (ICU) stay, but more cases of severe
      myoneuropathy, with methylprednisolone. There were virtually identical 60-day and
      180-day mortality rates for methylprednisolone and placebo in the largest RCT.
      Sub-group analysis of that study showed significantly higher mortality with
      methylprednisolone than with placebo when enrollment occurred > 13 days after
      onset of ARDS, but small sample size and differences in subject characteristics
      probably confound those results. Most meta-analyses demonstrated trends toward
      better survival with methylprednisolone, and, when restricted to patients
      enrolled in RCTs who received prolonged administration of methylprednisolone that
      was initiated within the first 14 days of ARDS, one meta-analysis demonstrated
      better survival with corticosteroids. Importantly, the aforementioned studies
      have methodological limitations, and the number of subjects enrolled was small.
      Experts differ in their recommendations regarding corticosteroids for late-stage
      ARDS, although one consensus group supported a "weak" recommendation of low-to
      moderate-dose corticosteroids for ARDS of < 14 days duration. If corticosteroids
      are administered, infection surveillance, avoidance of neuromuscular blockers,
      and gradual taper of corticosteroids are recommended.

PMID- 20040124
TI  - Should patients be able to follow commands prior to extubation?
AB  - The determination of optimal timing of liberation from mechanical ventilation
      requires a thorough assessment of multiple variables that can result in
      extubation failure. It is estimated that 5-20% of extubations fail. Traditional
      weaning parameters fail to predict extubation failure accurately, and attention
      has thus turned to improvements in extubation decision making through assessment
      of elements that may result in inability to protect the airway, such as excessive
      respiratory secretions, inadequate cough, and depressed mental status. Extubation
      is particularly controversial in patients with depressed mental status and
      inability to follow commands. When looking at univariate analyses, the reported
      studies are relatively evenly divided among those that did and did not find that
      inability to follow commands (ie, abnormal mental status) increases the risk of
      extubation failure. In addition, although extubation failure is a risk factor for
      poor overall outcome in heterogeneous populations, its impact on the patient
      failing with neurologic dysfunction has not been adequately determined. One
      limiting factor in all reported studies is how "inability to follow commands" is
      defined. The majority of studies use the Glasgow coma score, but this is
      difficult to determine in the intubated patient. Moreover, using the cutoff of
      Glasgow coma score >or= 8, favored by many authors, is questionable, as some
      patients with higher scores may be unable to follow commands. Currently it is
      agreed that many patients who are unable to follow commands, but have the ability
      to clear pulmonary secretions, can be safely extubated. A prospective, randomized
      trial using a more specific definition of "following commands" would certainly
      help remove some of the uncertainty in this patient population.

PMID- 20040125
TI  - Are sleep studies appropriately done in the home?
AB  - For many years the greatest barrier to the diagnosis and treatment of obstructive
      sleep apnea (OSA) was recognizing the disease. That obstacle is now fading as
      more physicians of all types are aware of the high prevalence of OSA and the
      consequences of untreated OSA. Sleep-laboratory polysomnography has long been
      considered the accepted standard for OSA diagnosis and has become a lucrative
      practice. This, unfortunately, has led to a concentration on diagnosis rather
      than on management of OSA. Although several brands of portable polysomnograph
      have been approved for home polysomnography, obstacles to reimbursement
      (primarily from government, but also from private payers) have prevented
      widespread home polysomnography. Over the last 2 decades many scientific studies
      have supported a strong correlation between the findings from home
      polysomnography and sleep-laboratory polysomnography. However, limited data are
      available from good outcomes-oriented studies, so controversy surrounds home
      polysomnography in the diagnosis of OSA. We review the evidence and debate
      whether sleep studies are appropriately done in the home.

PMID- 20040126
TI  - Should tracheostomy be performed as early as 72 hours in patients requiring
      prolonged mechanical ventilation?
AB  - Advances in treating the critically ill have resulted in more patients requiring
      prolonged airway intubation and respiratory support. If intubation is projected
      to be longer than several weeks, tracheostomy is often recommended. Tracheostomy
      offers the potential benefits of improved patient comfort, the ability to
      communicate, opportunity for oral feeding, and easier, safer nursing care. In
      addition, less need for sedation and lower airway resistance (than through an
      endotracheal tube) may facilitate the weaning process and shorten intensive care
      unit and hospital stay. By preventing microaspiration of secretions, tracheostomy
      might reduce ventilator-associated pneumonia. There is controversy, however, over
      the optimal timing of the procedure. While there have been many randomized
      controlled trials on tracheostomy timing, most were insufficiently powered to
      detect important differences, and systematic reviews and meta-analyses are
      limited by the heterogeneity of the primary studies. Based on the available data,
      we think it is reasonable to perform early tracheostomy in all patients projected
      to require prolonged mechanical ventilation. Unfortunately, identifying those
      patients can be difficult, and for many patient populations we lack the necessary
      tools to predict prolonged ventilation. We propose an early-tracheostomy decision
      algorithm.

PMID- 20040127
TI  - Should prone positioning be routinely used for lung protection during mechanical
      ventilation?
AB  - Prone positioning has been known for decades to improve oxygenation in animals
      with acute lung injury and in most patients with acute respiratory distress
      syndrome (ARDS). The mechanisms of this improvement include a more uniform
      pleural-pressure gradient, a smaller volume of lung compressed by the heart, and
      more uniform and better-matched ventilation and perfusion. Prone positioning has
      an established niche as an intervention to improve gas exchange in patients with
      severe hypoxemia refractory to standard ventilatory manipulations. Because the
      lung may be more uniformly recruited and the stress of mechanical ventilation
      better distributed, prone positioning has also been proposed as a form of lung
      protective ventilation. However, several randomized trials have failed to show
      improvements in clinical outcomes of ARDS patients, other than consistently
      better oxygenation. Because each of these trials had design problems or early
      termination, prone positioning remains a rescue therapy for patients with acute
      lung injury or ARDS.

PMID- 20040128
TI  - Is obstetric antiphospholipid syndrome a primary nonthrombotic, proinflammatory,
      complement-mediated disorder related to antiphospholipid antibodies?
AB  - Pregnancy loss is the main obstetrical complication of the obstetric
      antiphospholipid syndrome. Classically, such losses have been attributed to
      placental thrombosis and infarcts, although in many cases there is no evidence of
      decidual thrombosis or placental vasculopathy, and instead inflammatory signs are
      present. In addition, the prevalence of systemic thrombosis is low in obstetric
      antiphospholipid syndrome, suggesting an alternative pathogenesis. There is
      evidence that antiphospholipid antibodies, mainly beta2-glycoprotein-I/anti-beta2
      glycoproteina-I complexes, activate both classical and alternative complement
      pathways. Complement proteins may injure trophoblast cells, recruiting and
      activating monocytes and neutrophils. Free radicals and proteolytic enzymes could
      also attack trophoblastic cells, and amplification of the causal loop between
      tissue factor, inflammatory cells, and complement proteins could also be a
      factor. Overall, these diverse mechanisms may explain both inflammatory and
      thrombotic placental alterations. The role played by certain pro-inflammatory
      cytokines, mainly tumor necrosis factor-alpha, and the altered balance between
      angiogenic and anti-angiogenic factors remains to be clarified. In the end,
      obstetric antiphospholipid syndrome seems to be a clinical subset of classical
      APS. In these women, systemic thrombotic risk seems to be low. Current knowledge
      about inflammatory pathway involvement in obstetric antiphospholipid syndrome
      will permit us to modify the time to start heparin treatment, currently
      recommended to begin it as soon as possible after pregnancy confirmation. TARGET
      AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES:
      After completion of this article, the reader will be able to recall
      manifestations of obstetric antiphospholipid syndrome, describe nonthrombotic
      mechanisms that may affect obstetric outcomes in women with antiphospholipid
      syndrome, and predict changes in the evaluation and treatment of obstetric
      patients with antiphospholipid syndrome should inflammatory factors prove to be
      an important feature of antiphospholipid syndrome.

PMID- 20040129
TI  - Nasal bone in prenatal trisomy 21 screening.
AB  - The definitive diagnosis of fetal chromosomal abnormalities is only accomplished
      through tests that sample fetal tissue. These procedures--amniocentesis,
      chorionic villus sampling and cordocentesis--are invasive and carry with them the
      risks of bleeding, rupture of membranes, and even pregnancy loss. Current
      recommendations from the American College of Obstetricians and Gynecologists
      state that all women should be offered screening, regardless of maternal age.
      However, the exact screening test to apply to pregnant women is still a matter of
      debate. The goal of any screening method should be high detection (sensitivity)
      at low screen positive rates. Recent attention has focused on additional
      ultrasound markers to potentially improve the detection rate. Given that mid-face
      hypoplasia and a flattened nose are characteristic features of Down syndrome,
      investigators have tried to utilize its prenatal appearance--or more
      specifically, its absence--to enhance the detection of trisomy 21 (T21). The
      purpose of this document is to review the data on the utility of the nasal bone
      as a marker for T21. Particular attention will focus on its use in the first
      trimester versus second trimester as well as future directions for its potential
      incorporation into screening strategies. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
      article, the reader will be able to relate the prenatal and postnatal nasal
      phenotypes for Down syndrome, identify the potential role and pitfalls of nasal
      bone characteristics in screening for Down syndrome, and describe 3 different
      methods to define fetal nasal bone hypoplasia.

PMID- 20040130
TI  - Infectious disease and reproductive health: a review.
AB  - Human reproduction provides unique opportunities for the transmission of
      infectious agents. Furthermore, the mother and her offspring have distinct
      susceptibilities to infection at each stage of reproduction, from conception and
      gestation to parturition and the neonatal period. The impact of pathogens on
      reproduction can be mitigated or exacerbated depending on timing of acquisition
      during pregnancy. Similarly, factors such as maternal immune response,
      nutritional status, or concurrent infection may modify the effect of an
      infectious agent. In this review, we discuss the evidence--or lack thereof--for
      associations between infectious agents and reproductive problems at each stage of
      reproduction. We focus on well-substantiated associations, and consider several
      emerging or controversial associations. We discuss the challenges, limitations,
      and opportunities related to epidemiologic research on infectious disease and
      reproductive outcomes. TARGET AUDIENCE: Obstetricians & Gynecologists, Family
      Physicians. LEARNING OBJECTIVES: After completion of this article, the reader
      will be able to describe the potential mechanisms by which infectious agents may
      impact productive health, explain the public health impact of infectious diseases
      on reproductive health, and summarize the perinatal risks of infectious disease
      and relate this to treatment and prevention strategies in practice.

PMID- 20040131
TI  - Identification and quantitation of amphetamines, cocaine, opiates, and
      phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.
AB  - Analytical methods for measuring multiple licit and illicit drugs and metabolites
      in oral fluid require high sensitivity, specificity, and accuracy. With the
      limited volume available for testing, comprehensive methodology is needed for
      simultaneous measurement of multiple analytes in a single aliquot. This report
      describes the validation of a semi-automated method for the simultaneous
      extraction, identification, and quantitation of 21 analytes in a single oral
      fluid aliquot. The target compounds included are amphetamine, methamphetamine,
      3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4
      methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine,
      codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone,
      norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone,
      oxymorphone, and phencyclidine. Oral fluid specimens were collected with the
      Intercept device and extracted by solid-phase extraction (SPE). Drug recovery
      from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged
      91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography
      tandem mass spectrometry in the positive electrospray mode using ratios of
      qualifying product ions within +/-25% of calibration standards. Matrix ion
      suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5
      ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was
      demonstrated by testing oral fluid specimens from drug abuse treatment patients.
      Thirty-nine patients tested positive for various combinations of licit and
      illicit drugs and metabolites. In conclusion, this validated method is suitable
      for simultaneous measurement of 21 licit and illicit drugs and metabolites in
      oral fluid.

PMID- 20040132
TI  - High-throughput analysis of amphetamines in blood and urine with online solid
      phase extraction-liquid chromatography-tandem mass spectrometry.
AB  - An automated online solid-phase extraction-liquid chromatography-tandem mass
      spectrometry (SPE-LC-MS-MS) method for the analysis of amphetamines in blood and
      urine was developed and validated. Chromatographic separation was achieved on a
      Nucleodur Sphinx RP column with an LC gradient (a mixture of 10 mM ammonium
      formate buffer and acetonitrile), ensuring the elution of amphetamine,
      methamphetamine, MDMA, MDA, MDEA, PMA, and ephedrine within 11 min. The method
      was fully validated, according to international guidelines, using only 100 and 50
      microL of blood and urine, respectively. The method showed an excellent intra-
      and interassay precision (relative standard deviation < 11.2% and bias < 13%) for
      two external quality control samples (QC) for both matrices and three and two 'in
      house' QCs for blood and urine, respectively. Responses were linear over the
      investigated range (r(2) > 0.99, 2.5-400 microg/L for blood and 25-1000 microg/L
      for urine). Limits of quantification were determined to be 2.5 and 25 microg/L
      for blood and urine, respectively. Limits of detection ranged from 0.05 to 0.5
      microg/L for blood and 0.25 to 2.5 microg/L for urine, depending on the compound.
      Furthermore, the analytes and the processed samples were demonstrated to be
      stable (in the autosampler for at least 72 h and after three freeze/thaw cycles),
      and no disturbing matrix effects were observed for all compounds. Moreover, no
      carryover was observed after the analysis of high concentration samples (15,000
      microg/L). The method was subsequently applied to authentic blood and urine
      samples obtained from forensic cases, which covered a broad range of
      concentrations. The validation results and actual sample analyses demonstrated
      that this method is rugged, precise, accurate, and well-suited for routine
      analysis as more than 72 samples are analyzed non-stop in 24 h with minimum
      sample handling. The combination of the high-throughput online SPE and the well
      known sensitivity and selectivity assured by MS-MS resulted in the elimination of
      the bottleneck associated with the sample preparation requirements and provided
      increased sensitivity, accuracy, and precision.

PMID- 20040133
TI  - Development and validation of a high-performance liquid chromatography-tandem
      mass spectrometry method for the rapid simultaneous quantification of aconitine,
      mesaconitine, and hypaconitine in rat plasma after oral administration of Sini
      decoction.
AB  - A rapid, sensitive, and specific liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS-MS) method was developed and validated for
      simultaneous determination of aconitine (AC), mesaconitine (MA), and hypaconitine
      (HA), the three toxic constituents from Sini decoction (SND) in rat plasma. After
      the addition of citalopram as the internal standard (IS), plasma samples were
      basified with 100 microL 10% ammonium hydroxide, and then extracted with 1 mL
      ethyl acetate. Chromatographic separation was performed on a CN column (250 mm x
      4.6 mm, 5 microm) with a mobile phase of methanol/40 mM ammonium acetate/formic
      acid (950:45:5, v/v/v) at the flow rate of 1.0 mL/min. Analytes were determined
      in a triple-quadrupole mass spectrometer in the selected reaction-monitoring
      (SRM) mode using electrospray source with positive mode. The method was validated
      over the concentration ranges of 0.01-10 ng/mL for AC, MA, and HA. The variation
      coefficients were always < 15% for both intraday and interday precision for each
      analyte. Mean accuracies were also within +/-15%. The method was proved to be
      sensitive, rapid, specific, accurate, and reproducible. It has been successfully
      applied to the pharmacokinetics study on rats after oral administration of SND.

PMID- 20040134
TI  - Synthesis of trans- and cis-4'-hydroxylomustine and development of validated
      analytical method for lomustine and trans- and cis-4'-hydroxylomustine in canine
      plasma.
AB  - In veterinary medicine, lomustine has been successfull used primarily for the
      treatment of resistant lymphoma and also for the treatment of mast cell tumors,
      intracranial meningioma, epitheliotropic lymphoma, and histiocytic sarcoma in
      dogs either alone or in combination with other chemotherapeutic agents. Even
      though lomustine is commonly used in dogs primarily for the treatment of
      resistant lymphoma, there is no pharmacokinetics information available regarding
      this compound in dogs. In the present study, we developed and validated a simple
      high-performance liquid chromatography (HPLC) method with a one-step liquid
      liquid extraction procedure to detect and quantify lomustine and its two
      monohydroxylated metabolites (trans- and cis-4'-hydroxylomustine) in canine
      plasma for future pharmacokinetic studies. The HPLC-diode-array detection method
      reported here readily detects lomustine, cis-4'-hydroxylomustine, and trans-4'
      hydroxylomustine in canine plasma with a limit of detection of lomustine, cis-4'
      hydroxylomustine, and trans-4'-hydroxylomustine in plasma of about 10 ng/120
      microL, 5 ng/120 microL, and 5 ng/120 microL, respectively. The mean extraction
      efficiency values for lomustine, cis-4'-hydroxylomustine, and trans-4'
      hydroxylomustine were 73%, 90%, and 89%, respectively, from canine plasma samples
      on HPLC. The present study also provides stability information about lomustine
      and its two monohydroxylated metabolites in canine plasma and methanol solution
      stored at various conditions.

PMID- 20040135
TI  - Bioanalytical investigation of asarone in connection with Acorus calamus oil
      intoxications.
AB  - Preparations of the plant Acorus calamus (calamus or sweet flag) (A. calamus) are
      available via internet trade and marketed as being hallucinogenic. In 2003-2006,
      the Swedish Poisons Information Centre received inquiries about 30 clinical cases
      of intentional intoxication with A. calamus products. The present investigation
      aimed to identify alpha- and beta-asarone, considered active components of A.
      calamus, and metabolites thereof in urine samples collected in seven of these
      cases. To further aid the identification of asarone biotransformation products, a
      calamus oil preparation was incubated with the fungus Cunninghamella elegans,
      which is used as a microbial model of mammalian drug metabolism. Using gas
      chromatography-mass spectrometry (GC-MS) analysis in selected ion monitoring
      mode, alpha-asarone was detected in five urine samples at concentrations ranging
      between approximately 11 and 1150 microg/L and beta-asarone in four of those at
      approximately 22-220 microg/L. A previously identified asarone metabolite, trans
      2,4,5-trimethoxycinnamic acid (trans-TMC), was detected in the fungus broth by
      liquid chromatography-tandem mass spectrometry whereas cis-TMC was tentatively
      identified in the human urine samples. Using GC-MS, a hydroxylated asarone
      metabolite was identified both in fungus broth and urine samples. However, this
      study demonstrated no evidence for the presence of 2,4,5-trimethoxyamphetamine,
      claimed as a hallucinogenic component of A. calamus. The main clinical symptom
      reported by the patients was prolonged vomiting that sometimes lasted more than
      15 h.

PMID- 20040136
TI  - Short communication: Urinary excretion of 11-nor-9-carboxy-Delta(9)
      tetrahydrocannabinol in a pregnant woman following heavy, chronic cannabis use.
AB  - Differentiating new intake of drugs-of-abuse from residual drug excretion may be
      difficult, especially following chronic drug usage and for drugs with long
      elimination half-lives such as cannabis. In the present case, cannabis was found
      in the urine of a young pregnant woman following heavy and chronic cannabis use.
      She was warned that if she continued using cannabis while pregnant she would be
      forced to be hospitalized. She was subjected to serial urine testing with 2-7-day
      intervals. Urinary 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol (THCCOOH)
      concentrations, measured by liquid chromatography-mass spectrometry, declined
      from 348 to 3.9 ng/mL over a surprisingly long period of 12 weeks (84 days).
      Several algorithms for detecting new drug intake were applied during this time
      course; most indicated that the woman continued to smoke cannabis following the
      first urine test. The woman denied any use after the first specimen collection.
      In retrospect, her THCCOOH excretion profile supports her story. Algorithms for
      detecting new drug intake have been validated for occasional cannabis users only.
      We advise caution when interpreting urine test results from heavy, chronic
      cannabis users, especially when serious consequences are involved.

PMID- 20040137
TI  - Case report: Oxymorphone-involved fatalities: a report of two cases.
AB  - There has been an increased awareness of illicit opiate abusers using the
      narcotic oxymorphone (Opana) by inhalation. Many laboratory screening techniques
      currently in use cannot detect oxymorphone in blood or urine. Consequently,
      biological specimens containing low to moderate concentrations of oxymorphone
      will likely go undetected. The circumstances, pathology findings, and toxicology
      results of two fatalities involving oxymorphone are presented. An opiate
      confirmation gas chromatography-mass spectrometry (GC-MS) procedure, described in
      detail was able to detected, confirm, and quantify oxymorphone in both subjects.
      The blood concentrations were 0.05 mg/L (50 microg/L) and 0.12 mg/L (120
      microg/L).

PMID- 20040138
TI  - Letter to the editor: The possible role of levamisole in illicit cocaine
      preparations.

PMID- 20040140
TI  - The First Pan Pacific Symposium of Stem Cell Research.

PMID- 20040139
TI  - Letter to the editor: Richard Tecwyn Williams (1909-1979): An Appreciation.

PMID- 20040141
TI  - Forever young: how to control the elongation, differentiation, and proliferation
      of cells using nanotechnology.
AB  - Within the emerging field of stem cells there is a need for an environment that
      can regulate cell activity, to slow down differentiation or proliferation, in
      vitro or in vivo while remaining invisible to the immune system. By creating a
      nanoenvironment surrounding PC12 cells, Schwann cells, and neural precursor cells
      (NPCs), we were able to control the proliferation, elongation, differentiation,
      and maturation in vitro. We extended the method, using self-assembling nanofiber
      scaffold (SAPNS), to living animals with implants in the brain and spinal cord.
      Here we show that when cells are placed in a defined system we can delay their
      proliferation, differentiation, and maturation depending on the density of the
      cell population, density of the matrix, and the local environment. A combination
      of SAPNS and young cells can be implanted into the central nervous system (CNS),
      eliminating the need for immunosuppressants.

PMID- 20040144
TI  - Building a research infrastructure.

PMID- 20040145
TI  - Oral health: dental hygienists are key.

PMID- 20040146
TI  - Insurance as a predictor of dental treatment: a pilot study in the Savannah,
      Chatham County area.
AB  - PURPOSE: To assess patient compliance with the treatment prescribed by the
      dentist. METHODS: Data, which included age, gender, insurance status and a tally
      of accepted and rejected procedures by use of CDT (current dental terminology)
      codes, was extracted from a private dental office database. All patient
      identifiers were removed to insure internal reliability. Thirty procedure codes
      were investigated for each patient to determine compliance by individual code and
      categories which included preventative, radiographic and restorative procedures.
      RESULTS: Results indicated that the acceptance rate of dental exams by the
      insured and uninsured was greater than 80%. The comprehensive oral exam was most
      commonly rejected. The insured population had a 90% acceptance rate for, where
      the uninsured population had a 74.6% acceptance rate for the oral prophylaxis
      procedure. Radiographic procedures had an acceptance rate of 8.3% higher by
      insured patients than those uninsured. Crowns, bridges and dentures showed less
      difference in acceptance rates. CONCLUSIONS: A positive correlation exists
      between insurance status and patient acceptance of prescribed treatment.

PMID- 20040147
TI  - Predictors of success in dental hygiene education: a follow-up study.
AB  - PURPOSE: In 2002, a 6 year review of dental hygiene graduates from the Medical
      College of Georgia (1996 through 2001) was conducted to determine which criteria
      were the best predictors of success. Success was defined in terms of National
      Board Dental Hygiene Examination (NBDHE) score and dental hygiene GPA at
      graduation. The purpose of this follow-up study was to determine if a
      relationship exists between predicted success (using 2002 models) and actual
      success of entry-level baccalaureate degree students who graduated from 2002
      through 2007. METHODS: Two probability models of success were developed from a
      previous study of MCG dental hygiene graduates (1996 to 2001). Academic
      information from students (n=156) in the 2002 to 2007 classes was inserted into
      the two 2002 models to determine if there was a correlation between their actual
      and predicted success. RESULTS: Moderate correlation (r=.581, p=.01) was found
      when using the established MODEL 1 to predict dental hygiene GPA at graduation
      and moderate correlation (r=.465, p=.01) was found when using the established
      MODEL 2 to predict NBDHE scores. CONCLUSIONS: The authors concluded incoming GPA
      and total SAT((R)) Program score remain useful in predicting the success of
      students. However, when substituting incoming GPA with dental hygiene GPA at the
      end of the first year, even stronger correlations resulted in MODEL 1 (r=.957,
      p=.01) and in MODEL 2 (r=.694, p=.01). Based on these results, recommendations
      were made to keep current admissions criteria and to implement formal remediation
      for academically weaker students after completing the first year of the dental
      hygiene program.

PMID- 20040148
TI  - Motivational interviewing to decrease parental risk-related behaviors for early
      childhood caries.
AB  - PURPOSE: This small scale study examined if an individualized motivational
      interviewing (MI) approach to oral health education promoted positive changes in
      early childhood caries (ECC) risk-related behaviors of mothers enrolled in a
      Women, Infants and Children (WIC) Program. METHODS: Seventy-two mothers were
      recruited to complete pretest and posttest questionnaires 4 weeks apart. Mothers
      in the treatment group (n=40) experienced a counseling type session (MI) and
      follow-up telephone calls to promote positive oral health behaviors. RESULTS: No
      significant change was found in the 4 constructs measured: valuing dental health,
      permissiveness, convenience and change difficulty or openness to health
      information. Statistically significant positive changes were found in the
      treatment group only in number of times the children's teeth were cleaned or
      brushed (p=0.001) and the use of shared eating utensils (p=0.035). Other
      cariogenic feeding practices and use of sweets to reward or modify behavior were
      not significantly affected (p<0.05). CONCLUSIONS: In this group of WIC mothers,
      MI appeared to have a modest impact on some high-risk parental behaviors that
      contribute to ECC. This approach warrants further investigation to assess impact
      of an extended intervention program, parents from diverse populations and the
      feasibility of use of peer counselors in the public health setting.

PMID- 20040149
TI  - Women's health topics in dental hygiene curricula.
AB  - PURPOSE: Minimal inclusion of women's health topics in dental and dental hygiene
      curricula may not prepare dental health care workers to provide comprehensive
      health care to females. The purposes of these surveys in 2001 and 2007 were to
      investigate United States dental hygiene school curricula regarding inclusion of
      women's health topics in differing degree programs (associate/certificate,
      baccalaureate, associate/baccalaureate) and course status (required or elective).
      The surveys also identified sources used to obtain women's health topics,
      assessed faculty continuing education participation in women's health, determined
      satisfaction with current curricula, questioned if change was anticipated and if
      so in what topics, identified where students apply their knowledge about women's
      health and in what ways and reported progress of dental hygiene curricula over
      the 6 year time period. METHODS: Surveys were sent to dental hygiene program
      directors in 2001 (N=256) and in 2007 (N=288) asking them to complete the
      questionnaire. RESULTS: There was no statistically significant association
      between 2001 and 2007 survey results by degree or program setting. The
      educational issue, women's general health continuing education courses/topics
      completed by dental hygiene faculty in the past 2 years, showed a statistically
      significant difference during that time interval. No statistically significant
      difference existed between the survey years regarding topics on women's general
      health and oral health. Regardless of statistical significance, further details
      investigated percentage differences that may reveal relevant issues. CONCLUSIONS:
      These surveys establish a baseline of women's health topics included in dental
      hygiene curricula in order to assess knowledge of dental hygienists in practice.

PMID- 20040150
TI  - Pressure-sensitive adhesive properties of poly(N-vinyl pyrrolidone)/D,L-lactic
      acid oligomer/glycerol/water blends for TDDS.
AB  - In order to develop a new type of pressure-sensitive adhesive (PSA) for a
      transdermal drug-delivery system (TDDS), a quaternary blend (PDGW) composed of
      poly(N-vinyl pyrrolidone) (PVP), D,L-lactic acid oligomer (DLLAO), glycerol and
      water was prepared, in which glycerol and water were used as plasticizer. The
      effects of the number-average molecular weight (M(n)) of DLLAO and the contents
      of DLLAO and plasticizer on the PSA properties were studied. The results suggest
      that PDGW exhibits excellent PSA properties when M(n) of DLLAO is in the range of
      about 200-400 and the contents of DLLAO, glycerol and water are in the range of 5
      20, 15-25 and 20-35 wt%, respectively. The miscibility between PVP and DLLAO was
      investigated via DSC, TGA and FT-IR, and all results indicate that PVP has good
      miscibility with DLLAO due to strong hydrogen-bond interaction. The storage
      stability of PDGW also was studied and the results show that the PDGW matrix
      possesses stable properties over time. In addition, in vivo skin irritation of
      PDGW was investigated using rabbit as model animal, and the results show that the
      PDGW does not cause irritation to skin after topical application for 120 h.
      Therefore, the PDGW possesses excellent PSA properties and presents potential
      application in TDDS.

PMID- 20040151
TI  - Effects of the surface characteristics of polyhydroxyalkanoates on the metabolic
      activities and morphology of human mesenchymal stem cells.
AB  - Polyhydroxyalkanoates (PHAs) are a newer family of biomaterials for tissue
      engineering applications. The objective of this study is to investigate the
      behavior of human mesenchymal stem cells (hMSCs) grown on various PHA films. The
      surface characteristics of PHA co-polymer films were varied by the content of 3
      hydroxyvalerate (HV) or 3-hydroxyhexanoate (HHx) and by the film preparation
      methods such as compression-molding and solvent-casting. Hyaluronic acid (HA) was
      further applied to modify the surface properties of PHA membranes. As HV content
      increased, the crystallinity and the hydrophobicity of poly(3-hydroxybutyrate-co
      3-hydroxyvalerate) (PHBV) membranes decreased and the metabolic activity of hMSCs
      raised, although the distribution and morphology of hMSCs did not show
      significant variation. Hyaluronic acid (HA) coating on PHA membranes could
      improve the metabolic activity and reduce the death rate of hMSCs. Aggregates and
      spheroidal clusters of hMSCs were found on the surface of cast poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) membranes. The growth of hMSCs
      was remarkably influenced by various surface characteristics of the PHA films.

PMID- 20040152
TI  - Controlled release of stromal-cell-derived factor-1 from gelatin hydrogels
      enhances angiogenesis.
AB  - Controlled release of a chemokine, stromal-cell-derived factor-1 (SDF-1), could
      be achieved with gelatin hydrogels of release carrier. Gelatin was chemically
      derivatized to give it different electric charge and hydrophobicity. Among the
      derivatives, succinylated gelatin (Succ) of an anionic charge was the most
      suitable for preparation of the hydrogel in terms of SDF-1 release. The time
      profile of SDF-1 release from the hydrogel of succinylated gelatin could be
      controlled by changing the water content of hydrogel which could be modified by
      changing the conditions of hydrogel preparation. When evaluated after the
      subcutaneous implantation of Succ hydrogels incorporating SDF-1 or injection of
      SDF-1 solution, significantly stronger angiogenesis by the hydrogel was observed.
      The hydrogel implantation also enhanced the mRNA level of SDF-1 receptor at the
      site implanted. It is possible that the gelatin hydrogel enabled SDF-1 to be
      released locally, resulting in an enhanced angiogenesis at the site implanted.

PMID- 20040153
TI  - Effect of cyclic loading on in vitro degradation of poly(L-lactide-co-glycolide)
      scaffolds.
AB  - The in vitro degradation performance of porous scaffolds is very important in
      tissue engineering, especially the scaffold implanted in the environment
      imitating the repaired tissue. In this paper, the effect of cyclic loading on in
      vitro degradation of porous poly(L-lactide-co-glycolide) (PLGA) scaffolds was
      studied by incubating the samples in phosphate-buffered saline at 37 degrees C
      and pH 7.4 under dynamic conditions (cyclic loading) and static conditions
      (shaking water bath) for 12 weeks. The results showed earlier morphological
      variations and faster reduction in mass, dimensions and relative molecular mass
      of the scaffolds under dynamic conditions. Mechanical properties (the compressive
      modulus and the compressive strength) of the PLGA scaffolds under both conditions
      tended to increase in the first 3 weeks, but showed a decrease tendency
      afterward. The scaffolds under dynamic conditions were too brittle to be further
      characterized after degradation for 6 weeks, while those under static conditions
      endured degradation until week 8. The degradation mechanism of the PLGA scaffolds
      under cyclic loading was clearly explained and a three-stage degradation model
      based on the degradation behaviors of the scaffolds under two conditions was
      presented.

PMID- 20040154
TI  - Peroxidase activity of DNA aptamer-pt complexes prepared with cisplatin.
AB  - DNA aptamers carrying Pt nanoparticles prepared with cisplatin showed peroxidase
      enzymatic activity while retaining the specific binding ability of the aptamers.
      Optimal preparation conditions of DNA-Pt complex prepared with cisplatin were
      investigated on the synthesis at pH 7-11, a reaction time of 1-18 h and 90
      degrees C. The enzymatic reaction of DNA-Pt complex obeyed Michaelis-Menten
      kinetics. K(M) for the DNA-Pt complex was found to be of the same order as K(M)
      for hemin and hemin-DNA complex, but one order of magnitude higher than that of
      horseradish peroxidase. A sandwich type of DNA enzyme-linked aptamer assay (DLAA)
      using DNA-Pt complex successively detected target protein of thrombin. DLAA using
      DNA-Pt complex fractioned by ultrafiltration membranes having a molecular weight
      cut-off of 30 000 and 300 000 showed 1.9-times higher sensitivity than DLAA using
      DNA-Pt complex without fraction. The DNA-Pt complex having specific size was
      effective for the sensitive detection of thrombin in DLAA.

PMID- 20040155
TI  - Design of a matrix for cultured dermal substitute suitable for simultaneous
      transplantation with auto-skin graft: evaluation in animal test.
AB  - This study focused on the design of a matrix for a cultured dermal substitute
      (CDS). Two types of cross-linked spongy matrix were designed. The weight ratio of
      hyaluronic acid (HA) to a cross-linking agent was adjusted to 5:1 (c-5) or 15:1
      (c-15). Each HA spongy matrix was combined with collagen (Col) gel, forming 4
      groups: Group I, c-5 sponge and Col gel; Group II, c-5 sponge and Col gel with
      human fibroblasts; Group III, c-15 sponge and Col gel; and Group IV, c-15 sponge
      and Col gel with human fibroblasts. The physical properties of the matrix depend
      on the cross-linking conditions. In animal tests using T-cell-deficient F344
      rats, materials from Groups I-IV were transplanted onto a full-thickness skin
      defect, followed by auto-skin grafting. Commercially available artificial dermis
      composed of collagen sponge was employed as a control. Grafted skin survival in
      all groups was evaluated according to macroscopic and histological appearances 2
      weeks after transplantation. The take rate of auto-skin was higher in Groups I-IV
      than in control. The take rate of auto-skin was also higher for Groups II and IV
      than for Groups I and III. This finding indicates that CDS containing human
      fibroblasts is able to provide more suitable conditions for rat's auto-skin
      engraftment. The take rate of auto-skin in Group IV was >84%, showing the best
      results. This finding suggests that CDS comprising highly biodegradable matrix is
      acceptable for the engraftment of auto-skin, creating no physical barrier to
      interactions between the wound bed and auto-skin.

PMID- 20040156
TI  - Local delivery of tobramycin from injectable biodegradable polyurethane
      scaffolds.
AB  - Infections often compromise the healing of open fractures. While local antibiotic
      delivery from PMMA beads is an established clinical treatment of infected
      fractures, surgical removal of the beads is required before implanting a bone
      graft. A more ideal therapy would comprise a scaffold and antibiotic delivery
      system administered in one procedure. Biodegradable polyurethane (PUR) scaffolds
      have been shown in previous studies to promote new bone formation in vivo, but
      their potential to control infection through release of antibiotics has not been
      investigated. In this study, injectable PUR scaffolds incorporating tobramycin
      were prepared by reactive liquid molding. Scaffolds had compressive moduli of 15
      115 kPa and porosities ranging from 85-93%. Tobramycin release was characterized
      by a 45-95% burst (tuned by the addition of PEG), followed by up to 2 weeks of
      sustained release, with total release 4-5-times greater than equivalent volumes
      of PMMA beads. Released tobramycin remained biologically active against
      Staphylococcus aureus, as verified by Kirby-Bauer assays. Similar results were
      observed for the antibiotics colistin and tigecycline. The versatility of the
      materials, as well as their potential for injection and controlled release, may
      present promising opportunities for new therapies for healing of infected wounds.

PMID- 20040157
TI  - Mechanical performance and in vivo tests of an acrylic bone cement filled with
      bioactive sepia officinalis cuttlebone.
AB  - To promote osteointegration, bioactive cuttlebone particles containing collagen
      were used to fill an acrylic cement, varying filler concentration (0-50 wt%).
      Cuttlebone was characterized by X-ray diffraction, plasma atomic emission and FT
      IR. Mechanical properties of the filled cement were determined following ASTM
      procedures, included stress-strain, compression, bending, and fracture toughness
      tests. For in vivo tests, three groups of seven adult healthy rabbits were
      prepared to make an implant in the parietal bone of each one. For such groups (I
      III), the amount of filler in the cement was 0, 10 and 30 wt%, respectively.
      Mechanical results for the composites complied with norm requirements. However,
      as mechanical performance for composite with 50 wt% of filler decreased
      significantly, for the in vivo tests, such composite was excluded. In vivo tests
      showed that three implants of group I were loosely attached to the parietal bone,
      whereas all the implants made with cement containing cuttlebone particles (groups
      II and III) were firmly attached to the parietal bone, indicating
      osteointegration. These results clearly show the potential of this type of
      bioactive filler to be used for medical applications.

PMID- 20040158
TI  - Application of polyhydroxyalkanoates nanoparticles as intracellular sustained
      drug-release vectors.
AB  - Polyhydroxybutyrate (PHB), co-polyesters of 3-hydroxybutyrate and 3
      hydroxyhexanoate (PHBHHx), and polylactic acid (PLA) were used to prepare
      nanoparticles with average sizes of 160, 250 and 150 nm, respectively. A lipid
      soluble colorant, rhodamine B isothiocyanate (RBITC), was employed to study drug
      release behaviors from these nanoparticles. A high RBITC drug-loading efficiency
      of over 75% was achieved with all PHA nanoparticles prepared. Macrophage
      endocytosis led to an intracellular RBITC drug sustained release over a period of
      at least 20 days for PHB and PHBHHx nanoparticles, while PLA nanoparticles and
      free drug lasted only 15 days and a week, respectively. Polymer properties and
      particle sizes showed little effect on drug-release behavior. This study showed
      for the first time that PHB and PHBHHx can be used effectively to achieve
      intracellular controlled drug releases.

PMID- 20040159
TI  - Suicide mitigation: time for a more realistic approach.

PMID- 20040161
TI  - Beyond the specific child. What is 'a child's case' in general practice?
AB  - BACKGROUND: Too many abused and neglected children are being overlooked by GPs
      and other professionals who are in contact with the families. Some suggestions
      for a definition of 'a child in need' have been given, but the functionality of
      these definitions has not been tested in general practice. AIM: To describe the
      problems presented by GPs as cases with children in need during supervision, and
      from here to suggest an empirically-based definition of a child in need in
      general practice. DESIGN OF STUDY: A mixed-method evaluation design was used.
      SETTING: Twenty-one GPs, in Denmark, participated in supervision groups
      concerning cases with children in need in general practice. METHOD: The data were
      analysed via field notes and video recordings; case categorisation into sex,
      ethnicity, and developmental stages; thematically using the GPs' own
      descriptions; and a theoretically supported style. RESULTS: Analysis of the data
      led to the suggested definition of a case concerning 'a child in need' in general
      practice as one that directly or indirectly involves problems with a specific
      child, an as-yet unborn child, or one or both parents of a family currently or
      potentially threatening the wellbeing of the family or the child. CONCLUSION:
      Based on this analysis, one suggestion as to why some abused and neglected
      children are overlooked in general practice is that GPs often have to navigate in
      difficult indirect consultations, where there is a high risk of losing the
      overview.

PMID- 20040162
TI  - Child neglect: what does it have to do with general practice?

PMID- 20040163
TI  - NICE work: how NICE decides what we should pay for.

PMID- 20040164
TI  - Cost-effectiveness of shared pharmaceutical care for older patients: RESPECT
      trial findings.
AB  - BACKGROUND: Pharmaceutical care serves as a collaborative model for medication
      review. Its use is advocated for older patients, although its cost-effectiveness
      is unknown. Although the accompanying article on clinical effectiveness from the
      RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the
      Community over Time) trial finds no statistically significant impact on
      prescribing for older patients undergoing pharmaceutical care, economic
      evaluations are based on an estimation, rather than hypothesis testing. AIM: To
      evaluate the cost-effectiveness of pharmaceutical care for older people compared
      with usual care, according to National Institute for Health and Clinical
      Excellence (NICE) reference case standards. METHODS: An economic evaluation was
      undertaken in which NICE reference case standards were applied to data collected
      in the RESPECT trial. RESULTS: On average, pharmaceutical care is estimated to
      cost an incremental 10 000 UK pounds per additional quality-adjusted life year
      (QALY). If the NHS's cost-effectiveness threshold is between 20 000 and 30 000 UK
      pounds per extra QALY, then the results indicate that pharmaceutical care is cost
      effective despite a lack of statistical significance to this effect. However, the
      statistical uncertainty surrounding the estimates implies that the probability
      that pharmaceutical care is not cost-effective lies between 0.22 and 0.19.
      Although results are not sensitive to assumptions about costs, they differ
      between subgroups: in patients aged >75 years pharmaceutical care appears more
      cost-effective for those who are younger or on fewer repeat medications.
      CONCLUSION: Although pharmaceutical care is estimated to be cost-effective in the
      UK, the results are uncertain and further research into its long-term benefits
      may be worthwhile.

PMID- 20040165
TI  - Economic evaluation of nurse practitioners versus GPs in treating common
      conditions.
AB  - BACKGROUND: As studies evaluating substitution of care have revealed only limited
      evidence on cost-effectiveness, a trial was conducted to evaluate nurse
      practitioners as a first point of contact in Dutch general practices. AIM: To
      estimate costs of GP versus nurse practitioner consultations from practice and
      societal perspectives. DESIGN OF STUDY: An economic evaluation was conducted
      alongside a randomised controlled trial between May and October 2006, wherein 12
      nurse practitioners and 50 GPs working in 15 general practices (study practices)
      participated. Consultations by study practices were also compared with an
      external reference group, with 17 GPs working in five general practices without
      the involvement of nurse practitioners. METHOD: Direct costs within the
      healthcare sector included resource use, follow-up consultations, length of
      consultations, and salary costs. Costs outside the healthcare sector were
      productivity losses. Sensitivity analyses were performed. RESULTS: Direct costs
      were lower for nurse practitioner consultations than for GP consultations at
      study practices. This was also the case for direct costs plus costs from a
      societal perspective for patients aged <65 years. Direct costs of consultations
      at study practices were lower than those of reference practices, while practices
      did not differ for direct costs plus costs from a societal perspective for
      patients aged <65 years. Cost differences are mainly caused by the differences in
      salary. CONCLUSION: By involving nurse practitioners, substantial economic
      'savings' could be used for redesigning primary care, to optimise the best skill
      mix, and to cover the full range of primary care activities.

PMID- 20040166
TI  - Nurse staffing and quality of care in UK general practice: cross-sectional study
      using routinely collected data.
AB  - BACKGROUND: In many UK general practices, nurses have been used to deliver
      results against the indicators of the Quality and Outcomes Framework (QOF), a
      'pay for performance' scheme. AIM: To determine the association between the level
      of nurse staffing in general practice and the quality of clinical care as
      measured by the QOF. DESIGN OF THE STUDY: Cross-sectional analysis of routine
      data. SETTING: English general practice in 2005/2006. METHOD: QOF data from 7456
      general practices were linked with a database of practice characteristics, nurse
      staffing data, and census-derived data on population characteristics and measures
      of population density. Multi-level modelling explored the relationship between
      QOF performance and the number of patients per full-time equivalent nurse. The
      outcome measures were achievement of quality of care for eight clinical domains
      as rated by the QOF, and reported achievement of 10 clinical outcome indicators
      derived from it. RESULTS: A high level of nurse staffing (fewer patients per full
      time equivalent practice-employed nurse) was significantly associated with better
      performance in 4/8 clinical domains of the QOF (chronic obstructive pulmonary
      disease, coronary heart disease, diabetes, and hypertension, P = 0.004 to
      P<0.001) and in 4/10 clinical outcome indicators (diabetes: glycosylated
      haemoglobin [HbA(1C)] < or =7.4%, HbA(1C) < or =10% and total cholesterol < or
      =193 mg/dl; and stroke: total cholesterol < or =5 mmol/L, P = 0.0057 to P<0.001).
      CONCLUSION: Practices that employ more nurses perform better in a number of
      clinical domains measured by the QOF. This improved performance includes better
      intermediate clinical outcomes, suggesting real patient benefit may be associated
      with using nurses to deliver care to meet QOF targets.

PMID- 20040167
TI  - Effectiveness of nurse-delivered cardiovascular risk management in primary care:
      a randomised trial.
AB  - BACKGROUND: A substantial part of cardiovascular disease prevention is delivered
      in primary care. Special attention should be paid to the assessment of
      cardiovascular risk factors. According to the Dutch guideline for cardiovascular
      risk management, the heavy workload of cardiovascular risk management for GPs
      could be shared with advanced practice nurses. AIM: To investigate the clinical
      effectiveness of practice nurses acting as substitutes for GPs in cardiovascular
      risk management after 1 year of follow-up. DESIGN OF STUDY: Prospective pragmatic
      randomised trial. SETTING: Primary care in the south of the Netherlands. Six
      centres (25 GPs, six nurses) participated. METHOD: A total of 1626 potentially
      eligible patients at high risk for cardiovascular disease were randomised to a
      practice nurse group (n = 808) or a GP group (n = 818) in 2006. In total, 701
      patients were included in the trial. The Dutch guideline for cardiovascular risk
      management was used as the protocol, with standardised techniques for risk
      assessment. Changes in the following risk factors after 1 year were measured:
      lipids, systolic blood pressure, and body mass index. In addition, patients in
      the GP group received a brief questionnaire. RESULTS: A larger decrease in the
      mean level of risk factors was observed in the practice nurse group compared with
      the GP group. After controlling for confounders, only the larger decrease in
      total cholesterol in the practice nurse group was statistically significant (P =
      0.01, two-sided). CONCLUSION: Advanced practice nurses are achieving results,
      equal to or better than GPs for the management of risk factors. The findings of
      this study support the involvement of practice nurses in cardiovascular risk
      management in Dutch primary care.

PMID- 20040168
TI  - Time trends in preventive drug treatment after myocardial infarction in older
      patients.
AB  - Secondary preventive drug treatment in patients aged > or =60 years with a
      history of myocardial infarction was investigated for age-dependent differences
      in time trends. Sixteen general practices in the Netherlands participated.
      Preventive treatment with at least three of four drugs (antithrombotics, statins,
      beta-blockers, and/or angiotensin-converting enzyme inhibitors) increased
      significantly over time in all three age strata of older patients. Although the
      greatest relative increase (2.2 times greater) took place in patients aged > or
      =80 years, these patients consistently had most room for improvement.

PMID- 20040169
TI  - Does higher usage of low-cost statins correlate with a poorer achievement in
      cholesterol quality markers for secondary prevention?
AB  - There is pressure on primary care trusts, and therefore on GPs, to reach specific
      levels of use of low-cost statins as a proportion of total statin prescribing.
      This simple study looks at some markers of the quality of the results achieved. A
      correlation is found between a higher proportion of low-cost statin prescribing
      and lower achievement raising questions as to whether financial savings may be
      offset by poorer results.

PMID- 20040170
TI  - Quality of life measures.

PMID- 20040171
TI  - Antidepressant prescribing for older adults.

PMID- 20040173
TI  - RCGP autumn conference.

PMID- 20040174
TI  - Do we spend too much time with Nellie the Elephant?

PMID- 20040175
TI  - What about the context in family medicine?

PMID- 20040177
TI  - Circumcision: a religious obligation or 'the cruellest of cuts'?

PMID- 20040178
TI  - Health and wellbeing?

PMID- 20040181
TI  - Turning a blind eye to crime: health professionals and the Sexual Offences Act
      2003.

PMID- 20040179
TI  - Saplings into oaks.

PMID- 20040182
TI  - A stitch in time.

PMID- 20040183
TI  - [Use of Southern Blot/Hybridization technique associated to polymerase chain
      reaction to improve the sensitivity in the diagnosis of hemoplasma infections in
      domestic cats].
AB  - The aim of this study was to determine whether Southern Blot/Hybridization (SB)
      associated to Polymerase Chain Reaction (PCR) improves the sensitivity in the
      detection of hemoplasma DNA in domestic cats (Felis catus). Whole blood was
      collected in tubes containing the anticoagulant ethylenediamine tetra-acetic acid
      and DNA extracted from 149 animals. PCR was performed using species specific
      primers to amplify the 16S ribosomal RNA subunit of Mycoplasma haemofelis and
      'Candidatus M. haemominutum' from these samples. Hybridization was performed
      using a 16S rDNA probes chemically labeled and the results were visualized using
      a chemiluminescent substrate addition followed by autoradiography. Eighteen
      (12.1%) of the 149 tested samples had a positive PCR result for hemoplasma
      species DNA. SB/hybridization technique showed that 24/149 (16.1%) samples were
      positive for hemoplasmas, confirming the 18 PCR-positive results and reveling six
      additional positive animals (p<0.001). SB/hybridization method with specific
      probes was more sensitive than PCR performed alone, being complimentary to this
      technique to diagnose infections caused by feline hemoplasmas.

PMID- 20040184
TI  - [Selection of isolates of entomopathogenic fungus Beauveria bassiana
      (Ascomycetes: Clavicipitaceae) for control of Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae)].
AB  - This study was carried out to select isolates of the entomopathogenic fungus
      Beauveria bassiana with pathogenic potential to control the Rhipicephalus
      (Boophilus) microplus tick. The effectiveness of thirty isolates was first tested
      at a concentration of 5 x 108 conidia.mL(-1). Of these, eight were evaluated
      (IBCB01, IBCB02, IBCB07, IBCB17, IBCB21, IBCB74, IBCB149, IBCB165) and showed an
      effectiveness between 90 and 99%; thirteen (IBCB03, IBCB14, IBCB16, IBCB24,
      IBCB95, IBCB97, IBCB102, IBCB141, IBCB146, IBCB147, IBCB150, IBCB154, IBCB157)
      between 80 and 89,5%; six (IBCB47, IBCB75, IBCB84, IBCB145, IBCB161, IBCB164)
      between 70 and 79%, and only two (IBCB13 and IBCB143) had lower pathogenicity
      (70% or below). In the second step of the study, the five more effective strains
      in the first phase of the experiment (IBCB01, IBCB07, IBCB21, IBCB66, IBCB165)
      were analyzed comparatively. Based on in vitro results, it can be concluded that
      IBCB66 and IBCB21 are the isolates with higher potential for field control of R.
      (B.) microplus. IBCB01, IBCB07, IBCB21, IBCB66 e IBCB165 isolates were submitted
      to a conidial production test using a rice-based substrate. The best mass
      production of the entomopathogenic fungus was obtained with the IBCB66 strain.

PMID- 20040185
TI  - [Dirofilaria immitis (Leidy, 1856) in the neighborhood of a feline case: a study
      about the transmission].
AB  - Dirofilaria immitis preferably infects canids and can, in lower frequency, be
      found in cats (Felis catus Linnaeus, 1758). The parasite may be transmitted by
      various Culicidae species. Motivated by an autochtone feline heartworm case
      diagnosed in the region of Engenho Novo - RJ (S 22 degrees 90' e WO 43 degrees
      27'), the following issues were surveyed: 1) the local Culicidae fauna and; 2)
      the ocurrence of microfilaremic dogs. The mosquito study was conducted from April
      2003 through May 2004, by peri-domiciliary and intra-domiciliary captures. A
      total of 672 mosquitoes (female) of the following species were caught: Aedes
      aegypti (Linnaeus) (561/672-83.5%); Culex quinquefasciatus Say (96/672-14.3%);
      Aedes (Oc.) scapularis (Rondani) (12/672-1.8%) and Aedes albopictus (Skuse)
      (3/672-0.4%). Only A. aegypti and C. quinquefasciatus specimens were captured
      year-round. A total of 235 canine blood samples were collected during the
      Campanha de Vacinacao "Rio Sem Raiva" in October 2003. No microfilaria could be
      found in any of the examined samples (Knott s and NAN techniques), even though
      only 3.4% of the dogs received chemoprophylaxis and the majority of them
      frequently traveled to endemic areas. The presence of vectors associated to a
      possible dog mobility, may have provided the right scenario for the feline D.
      immitis infection to happen in the studied area.

PMID- 20040186
TI  - [Diversity of wild and domestic mammal's intestinal helminths from the Caatinga
      of the Parque Nacional Serra da Capivara, Southeast of Piaui, Brazil].
AB  - Biodiversity studies allow ecosystem assessment and monitoring of environmental
      changes and impacts. Parasite diversity could reflect the host/ parasite
      coevolutionary process and the environment changes that permit the loss, gain or
      maintenance of species. This survey used species/morphotypes of helminths eggs
      found in feces from seven wild mammal species (the groups Dasypodidae and Large
      Cats, and Tamandua tetradactyla, Cebus apella, Alouatta caraya, Cerdocyon thous,
      Pecari tajacu) and from two domestic species (Canis familiaris and Sus scrofa),
      which occur within the Serra da Capivara National Park (PNSC) and surrounding
      areas in order to analise the diversity of mammal intestinal helminths. This work
      used the helminthological fauna findings of wild and domestic mammals, to
      consider a possible helminth flux between these two host groups using Unweighted
      Pair Group Method with Arithmetic Mean (UPGMA) of the hosts based on
      helminthological fauna composition. The results indicate that the region of the
      PNSC still maintains environmental conditions that still keep wild mammal
      helminthological fauna composition different from the one found for domestic
      mammals.

PMID- 20040187
TI  - [Inquiry of antibodies anti-Neospora caninum in dairy cattle, dogs and rural
      workers of the south-west region of Mato Grosso State].
AB  - Considering the importance of neosporosis in the animal health and production,
      the frequency of antibodies to Neospora caninum was evaluated in dairy cattle of
      the Southwestern region of Mato Grosso State, Brazil, in addition to serum
      samples obtained from dogs and humans living in the farms. A total of 1036 serum
      samples were analyzed, from which 932 were from dairy bovine females, 37 from
      dogs and 67 from humans, from 24 farms and examined by the indirect fluorescent
      antibody test (IFAT). Reactive human serum samples were retested by Western-
      blotting to confirm the results. Antibodies to N. caninum were found in 499
      cattle sera (53.5%), with at least one positive in each farm, 25 dog sera (67.6%)
      and seven human sera (10.5%). There was no significant difference in the number
      of positive cattle sera according to age group. The results indicate a wide
      dissemination of N. caninum in the studied region.

PMID- 20040188
TI  - [Determination of LC 90 and LT 90 of IBCB66 Beauveria bassiana (Ascomycetes:
      Clavicipitaceae) isolate for Rhipicephalus (Boophilus) microplus (Acari:
      Ixodidae) control].
AB  - The objective of this research was to evaluate the pathogenicity and the
      virulence of the IBCB66 isolate of Beauveria bassiana on infected larvae of
      Rhipicephalus (Boophilus) microplus. The IBCB66 fungus strain was used as
      standard isolates of B. bassiana against R. (B.) microplus larvae. The larval
      bioassay tests using the IBCB66 isolate were carried out to determine the (Lethal
      Concentration) LC50, LC90, (Lethal Time) LT50 and LT90. The IBCB66 fungus strain
      was tested at six different concentrations (5x10(6), 10(7), 5x10(7), 10(8),
      5x10(8) and 10(9) conidia.mL(-1)) to determine the percentage of larval
      mortality. In addition, a Probit analysis was also performed. Total larval
      mortality was observed eighteen days after the beginning of the test in the group
      treated with 5x10(9) conidia.mL(1). The LC50 and LC90 were 3x10(7) and 5x10(8)
      respectively and the LT50 and LT90 were 10 and 16 days.

PMID- 20040189
TI  - Possible acquired resistance of dogs successively infested by Amblyomma
      cajennense (Fabricius, 1787) (Acari: Ixodidae) nymphs.
AB  - The present study aimed to evaluate the occurrence of immune resistance in dogs
      successively infested with Amblyomma cajennense nymphs. Five animals were
      submitted to four consecutive infestations with A. cajennense nymphs, at fourteen
      day intervals. For each infestation, 50 nymphs were used per animal and data on
      the parasitic and non-parasitic periods were recorded. The average recovering
      rate of engorged nymphs in the successive infestations were 52.0, 29.2, 9.6 and
      12.8%, respectively, with a significant reduction (p<0.05) of this parameter from
      the second infestation onwards. The modal drop-off day of engorged nymphs was Day
      4 of parasitism in all infestations. The average mortality rates of nymphs seen
      on the first, second, third and fourth infestations were 3.6, 3.2, 2.0 and 2.8%,
      respectively, with no significant differences among them (p<0.05). In addition,
      no significant differences were seen among the ecdysis rates for specimens
      recovered from successive parasitic challenges. The study results suggest that
      the acquired resistance of infested dogs had a negative effect on recovery rate
      of A. cajennense nymphs; however, it did not affect the other biological
      parameters evaluated.

PMID- 20040190
TI  - [Anthelmintic activity of aqueous extract of Zanthoxylum rhoifolium Lam. leaves
      (Rutaceae)].
AB  - The study evaluated the anthelmintic activity of aqueous extract of Zanthoxylum
      rhoifolium leaves in two experiments. In vitro test, cultures of goat fecal
      samples were treated with different concentrations of extract (134.5 to 335.0
      mg.mL(-1)). In vivo test was composed of 20 sheep: G1: treated with 0.63 g.kg(
      1), during four days; G2: same dose, for eight days; G3: ivermectin (200
      microg.kg(-1)) and G4 untreated group. In vitro results showed a reduction of
      Haemonchus spp, Trichostrongylus spp. and Oesophagostomum spp. larvae greater
      than 95% in the concentrations between 335.0 and 193.7 mg.mL(-1). Faecal egg
      counting reduction was 51, 56 and 90% in G1, G2 and G3, respectively, while
      immature stages and adults ranged from 0 to 91% in G1 and from 26 to 94% in G2.
      Ivermectin effectiveness was 99% for L4 and L5 of H. contortus and 100% for other
      nematodes species. Clinical and biochemical parameters have remained in the
      normality and histophatologic analyses did not show alteration suggesting absence
      of toxicity. Although the great effectiveness of Z. rhoifolium leaves extract in
      vitro test, it displayed poor efficiency in vivo regarding gastrointestinal
      nematodes reduction.

PMID- 20040191
TI  - [Factors associated the seropositivity for Babesia, Toxoplasma, Neospora e
      Leishmania in dogs attended at nine veterinary clinics in the municipality of
      Lavras, MG].
AB  - The aim of the present study was to determine the frequency and evaluate the
      infuence of age, sex and breed in seropositivity anti-Babesia canis, Toxoplasma
      gondii, Leishmania (L.) chagasi and Neospora caninum, by means of the indirect
      immunofuorescence antibody test (IFAT), in serum samples collected from dogs
      attended in nine private veterinary clinics in municipality of Lavras, Minas
      Gerais, Brazil, from August 2000 to April 2002. Of 300 dogs, 73.3% were
      seropositive (IFAT>or=1:80) to B. canis, and there was a signifcant increase
      (p<0.05) of the reagent in adult animals when compared with young. Only one dog
      (0.3%) from Belo Horizonte there was antibodies anti-L. (L.) chagasi
      (IFAT>or=1:40). T. gondii, of 218 dogs, 60.7% were positive (IFAT>or=1:16). In
      228 serum samples, 3.1% were positive (IFAT>or=1:50) to N. caninum. Infections to
      B. canis and T. gondii occur as endemic form in dogs examined at private
      veterinary clinics in Lavras. Tere is no evidence that there are autochthonous
      cases of canine visceral leishmaniosis in Lavras. Besides this the infection by
      N. caninum is uncommon in dogs breed at the urbane zone of the municipality.

PMID- 20040192
TI  - [In vitro analysis of amitraz efficacy against Rhipicephalus (Boophilus)
      microplus (Canestrini, 1887) populations of southern region of Rio Grande do Sul
      state].
AB  - Commercial formulation of the amitraz is the most used acaricide in the southern
      region of Rio Grande do Sul State, however scientific data about the efficacy of
      these products in this region are sparse. The aim of the present study was to
      evaluate the frequency of R. (B.) microplus populations resistant to amitraz
      acaricides in the Southern region of Rio Grande do Sul State. So, the efficacies
      of five commercial products containing amitraz were compared. Results showed that
      the efficacy of amitraz acaricides was lower than 69% in 23% of studied
      populations. Nearly 29% of the tick samples showed an acaricide efficacy equal to
      zero, suggesting the presence of a high level of resistance to amitraz. Moreover,
      the most used commercial product in the region showed the lowest efficacy index.
      These results alert about the possible spreading of resistant on tick populations
      and justify research directed toward the search for alternative products to
      control this parasite.

PMID- 20040193
TI  - [Comparison of nested-PCR with blood smear examination in detection of Ehrlichia
      canis and Anaplasma platys in dogs].
AB  - The clinical signs of Ehrlichia canis and Anaplasma platys infection are similar,
      and the diagnosis of these pathogens made by stained blood smears is poor due
      sensibility and specificity. On the other hand, the molecular diagnosis is highly
      sensitive and specific and nested-PCR have been optimized for accurate diagnosis
      these pathogens in dogs. At the veterinary teaching hospital, whole-blood samples
      with EDTA were obtained from 100 dogs and smears were made from blood samples for
      evaluation for intracellular parasites. For each sample, DNA was extracted and
      submitted to nPCR analysis for detection of E. canis and A. platys. The results
      of stained blood smears showed 9% of the animals were positive for E. canis and
      21% for A. platys. Regarding of nPCR analysis, 57 and 55% of dogs were positive
      for E. canis and A. platys respectively. As compared to a nested PCR, the stained
      blood smears revealed false-negative results for both E. canis and A. platys. The
      results indicate that the nPCR is highly sensitive and specific for detection of
      both pathogens and the molecular diagnosis could be more useful at veterinary
      hospital.

PMID- 20040194
TI  - [Compatibility of Beauveria bassiana (Ascomycetes: Clavicipitaceae) with
      chemicals acaricides used in the control of cattle tick].
AB  - The purpose of the present study was to assess compatibility between IBCB66 and
      IBCB21 isolates of Beauveria bassiana and acaricides: Flumethrin+Coumaphos,
      Deltamethrin, Dichlorvos+Cypermethrin, Dichlorvos+Chlorpyrifos, Cypermethrin High
      Cis, Dichlorvos+Cypermethrin High Cis, Cypermethrin and Amitraz, utilized on the
      control of Rhipicephalus (Boophilus) microplus in our country. The effect of
      commercial products on the isolates was assayed according to observation of
      vegetative growth, conidia production, and viability of strains of B. bassiana
      fungus. With concerning about IBCB66 isolate, products Deltamethrin, Cypermethrin
      High Cis and Amitraz were compatible, not affecting the entomopathogen
      development. Product Cypermethrin was toxic, and products Flumethrin+Coumaphos,
      Dichlorvos+Cypermethrin, Dichlorvos+Chlorpyrifos and Dichlorvos+Cypermethrin High
      Cis were very toxic. In regard to IBCB21 isolate, products Flumethrin+Coumaphos,
      Dichlorvos+Cypermethrin, Dichlorvos+Chlorpyrifos, Cypermethrin High Cis,
      Dichlorvos+Cypermethrin High Cis and Cypermethrin were very toxic and product
      Amitraz was toxic. From the acaricides evaluated, product Deltamethrin was the
      single agent that did not produce toxic effect on the entomopathogen.

PMID- 20040195
TI  - [Occurrence of anti-Toxoplasma gondii antibodies in ovine from urban and
      periurban areas from Curitiba, Parana State].
AB  - This study evaluated occurrence of the Toxoplasma gondii infection in ovine from
      urban and periurban areas of Curitiba, State of Parana, Southern of Brazil. Blood
      samples from 167 sheep from three farms were collected. ELISA assay was used to
      detect IgG anti-Toxoplasma gondii antibodies. Of 167 ovine samples, 43 (25.75%)
      were positive. The parasite is widespread among sheep from urban and periurban
      areas of Curitiba.

PMID- 20040197
TI  - [Occurrence of Neobenedenia melleni (Monogenea: Capsalidae) in Trichiurus
      lepturus (Perciformes: Trichiuridae), naturally infested of coastal zone of Rio
      de Janeiro, Brazil].
AB  - Neobenedenia melleni (MacCallum, 1927) is a widely spread pathogen in teleost
      maricultures with a very low host specificity. Between July of 2006 to June of
      2007, 120 specimens of Trichiurus lepturus Linnaeus, 1758 were acquired of local
      fishermen in the Guanabara Bay (22 degrees 57' S and 42 degrees 41' W), State of
      Rio de Janeiro, Brazil, to the study of the parasite fauna. The surface of the
      host body was scraped and the monogeneans obtained were identified as N. melleni,
      which showed prevalence of 8.3% and mean intensity of infection 1.2+/-0.42. Data
      about morphology of the specimens collected were included herein. Neobenedenia
      melleni is recorded by the first time parasitizing on a wild host from the
      Brazilian coastal zone.

PMID- 20040196
TI  - [Larval Anisakidae in musculature of Pagrus pagrus from the State of Rio de
      Janeiro, Brazil].
AB  - Musculature of 36 specimens of Pagrus pagrus from the coastal zone of the State
      of Rio de Janeiro were examined to study larval of anisakid nematodes between
      January and May 2008. A total of 24 larval of Anisakis sp., Contracaecum sp.,
      Hysterothylacium sp. and Raphidascaris sp. were collected infecting seven fishes
      (19.4%). Larval Hysterothylacium sp. and Contracaecum sp. showed highest
      prevalence and Hysterothylacium sp. highest parasite abundance. This is the first
      record of larval anisakids in the somatic musculature of P. pagrus.

PMID- 20040198
TI  - First report of Strongyloides sp. (Nematoda, Strongyloididae) in Leopardus
      tigrinus (Carnivora: Felidae) in the municipality of Botucatu, State of Sao
      Paulo, Brazil.
AB  - The present study reports the first case of infection by Strongyloides sp. in
      Leopardus tigrinus in the municipality of Botucatu, State of Sao Paulo, Brazil.
      Feces of the infected L. tigrinus specimen were cultivated in sterilized equine
      feces and a cat (Felis catus domesticus) was experimentally infected with three
      thousand infective L3 subcutaneous route, in order to identify the Strongyloides
      species involved in the parasitism. Parthenogenetic females recovered from the
      experimental animals were analyzed but comparison between the biometric data
      found and the data in the literature did not enable identification of the
      species. This is the first report on the occurrence of Strongyloides sp. in L.
      tigrinus.

PMID- 20040199
TI  - [Struthiolipeurus rheae Harrison, 1916 (Phthiraptera: Philopteridae) infesting
      ostriches (Struthio camelus) in one farming in the Municipality of Tres Rios,
      RJ].
AB  - In Brazil ostriches farming began at the end of 20th Century, to supply the
      international market of meat, feathers and leather. Feathers are economically
      important to industry and artisanal sectors. Lice can cause intense pruritus that
      depending on the intensity of infestation can lead to depreciation of feathers.
      In Rio de Janeiro there are unknown species of lice infesting ostriches. Thus the
      objective of this study was to identify the lice that happen in birds from
      commercial farms in the Municipality of Tres Rios. From 2003 to 2006 ostriches
      were monthly examined for the presence of ectoparasites. When infestations were
      detected some feathers were removed, placed into plastic bags and sent to the
      laboratory for further analysis. After removed from feathers, ectoparasites were
      examined using a stereoscope, followed by clarification in 10% potassium
      hydroxide and dehydrated in ethanol. Permanent slides were mounted in natural
      Canada balsam for observation in optical microscope. Based on observed
      characteristics, it was possible to determine that collected specimens belong to
      the species Struthiolipeurus rheae.

PMID- 20040200
TI  - [In vitro evaluation of nematode predacious fungus Duddingtonia fagrans on
      cyathostomes infective larvae of equines (Nematoda: Cyathostominae)].
AB  - The predatory capacity of one isolate of nematode-trapping fungus Duddingtonia
      flagrans (AC001) on infective larvae of cyathostomes was evaluated in
      laboratorial conditions in medium water-agar 2% (WA 2%). There was significant
      reduction (p<0.01) of 93.64% in the average of infective larvae of cyathostomes
      recovered of medium WA 2% at seven day. These results show that the isolated
      AC001 could be used in the biological control of cyathostomes of horses.

PMID- 20040201
TI  - Prevalence of equine Piroplasmosis and its association with tick infestation in
      the State of Sao Paulo, Brazil.
AB  - Serum samples were collected from 582 horses from 40 stud farms in the State of
      Sao Paulo and tick (Acari: Ixodidae) infestations were evaluated on them. Serum
      samples were subjected to the complement fixation test (CFT) and a competitive
      inhibition ELISA (cELISA) for Babesia caballi and Theileria equi. Logistic
      regression analyses were performed to construct multivariate models that could
      explain the dependent variable (horses positive for B. caballi or T. equi) as a
      function of the independent variables (presence or abundance of each one of the
      tick species found on the farms). A higher overall prevalence of B. caballi
      (54.1%) than of T. equi (21.6%) was found by the two tests. The ticks Dermacentor
      nitens Neumann, 1897, Amblyomma cajennense (Fabricius, 1787) and Rhipicephalus
      (Boophilus) microplus (Canestrini, 1887) were present on horses on 38 (95%), 20
      (50%), and 4 (10%) farms, respectively. Infestations by D. nitens were
      statistically associated with B. caballi-positive horses on the farms by either
      the CFT or cELISA. Infestations by A. cajennense were statistically associated
      with T. equi-positive horses on the farms by either CFT or cELISA.

PMID- 20040202
TI  - Comparison of efficiency and reproductive aptitude indexes between a reference
      and field strains of the cattle tick Rhipicephalus (Boophilus) microplus, in
      Sinaloa, Mexico.
AB  - The objective of this work was to study the reproductive behavior of two strains
      of R. (B.) microplus, one wild-caught (Native) and one reference strain (Media
      Joya) for two years, measuring the reproductive efficiency index (REI) and
      reproductive aptitude index (RAI). Engorged ticks from each strain were collected
      monthly from February 2002 to February 2004. These were weighed and kept in the
      laboratory until egg-laying. Oogenic masses were individually weighed and
      incubated until larvae emergence. REI and RAI were calculated from each sample,
      grouping ticks by weight in 100 mg range classes. An analysis of variance and
      Duncan's multiple rank tests were carried out on the data (P < 0.05). Pearson's
      correlation coefficients were estimated (P < 0.01) in order to determine the
      relationship between engorgement weight and the weight and number of laid and
      hatched eggs. The Native strain showed a higher engorgement weight than Media
      Joya strain. In both strains REI and RAI were similar in all weight classes; with
      a quadratic tendency in Media Joya and linear-quadratic in the Native strain (P <
      0.05). Significant differences where observed when REI and RAI of both strains
      were compared along the duration of the study (P < 0.01) with the Native strain
      performing better in both indexes, including better performance during the dry
      season. All parameters studied showed highly significant correlation; eggs laid
      and eggs hatched were notably highly correlated, 0.94 and 0.91, for Media Joya
      strain and Native strain respectively.

PMID- 20040203
TI  - Diagnosis of Neospora caninum in bovine fetuses by histology,
      immunohistochemistry, and nested-PCR.
AB  - Neospora caninum, a cause of abortion and stillbirth in cattle, was studied by
      histology, immunohistochemistry, and nested-PCR, using primers from the Nc5
      region of the genomic DNA (PCR PLUS) and primers from the ITS1 region of the
      ribosomal DNA (PCR JB). A total of 105 fetal samples sent to the Centro de
      Pesquisa e Desenvolvimento de Sanidade Animal do Instituto Biologico from January
      2006 to May 2008 were examined for evidence of N. caninum. Histological
      examination revealed 71.4% with non-suppurative inflammation in the heart, lung,
      liver, kidney, placenta, and brain. Immunohistochemistry detected infections in
      8.6% of the samples, mainly in the brain, placenta, and heart. Nested-PCR JB
      revealed 6.7% with infections, while nested-PCR PLUS returned 20.9% positive
      results, mainly in brain and placenta, and in the pooled liver and heart. Kappa
      statistics demonstrated little agreement among the three techniques. The three
      methods are complementary, since they have distinct diagnostic characteristics
      and were combined to give a positivity rate of 24.8%.

PMID- 20040204
TI  - Molecular diagnosis of Anaplasmataceae organisms in dogs with clinical and
      microscopical signs of ehrlichiosis.
AB  - Ehrlichioses are important emerging zoonotic tick-borne diseases that can affect
      both animals and humans. Clinical manifestations of ehrlichiosis caused by
      different members of Anaplasmataceae in dogs are similar to each other and to
      other diseases showing systemic manifestation. The observation of inclusions in
      white blood cells and in platelets cannot be used to confirm the Anaplasmataceae
      etiologic agent of the disease. In this work we assessed the presence of
      Anaplasmataceae agents in 51 dogs from two different cities (Jaboticabal and
      Campo Grande) showing clinical and microscopical diagnosis of ehrlichiosis, by
      using molecular techniques. Anaplasmataceae DNA were amplified in 46/51 (90.2%)
      of the blood samples; 22 (40%) samples from Jaboticabal and 10 (18.2%) from Campo
      Grande were positive for E. canis nPCR. Anaplasma platys DNA was amplified in 2
      samples from Jaboticabal and in 11 from Campo Grande. Phylogenetic analysis of E.
      canis and A. platys DNA confirmed the infection agent and showed that PCR is the
      most reliable method to diagnose ehrlichial infection.

PMID- 20040205
TI  - [Ectoparasites and intestinal helminths in Felis catus domesticus from Lages
      city, SC, Brazil and social-economical and cultural aspects of owners of family
      pets].
AB  - The purpose of this research was to determinate the prevalence of ectoparasites
      and gastrointestinal (GI) parasites in domiciliated cats, from central and
      peripheral region, of Lages city, Santa Catarina State and also characterize the
      economic, social and cultural status of families' pet owners. From the period of
      December 2005 to December 2006, 600 questionnaires were distributed to pet owners
      of Lages city and ectoparasites and faeces were collected. The prevalence of
      ectoparasites was 13.8% (28/203) and for GI parasites was 37.8% (42/111). The
      prevalence of parasites in domiciliated cats from the peripheral region were
      bigger than in the central region. The ectoparasites observed were
      Ctenocephalides felis felis, C. canis and Ctenocephalides hybrid (C. felis felis
      x C. canis). The intestinal helminths eggs observed in cats faeces were
      Ancylostoma spp., Toxocara sp., Trichuris sp., Taeniidae family and Oncicola sp.
      In the peripheral region, the largest number of positive animals belonged to
      owners of low-income wage and low education The peripheral region population are
      over exposed to potencial zoonotic agents.

PMID- 20040206
TI  - [Anthelmintic activity of aqueous and ethanolic extracts of Morinda citrifolia
      fruit on Ascaridia galli].
AB  - The anthelmintic activity of aqueous and ethanolic extracts of Morinda citrifolia
      fruit (noni) was evaluated in chicken naturally infected by Ascaridia galli. The
      anthelmintic activity in vitro was determined in adult parasites. The aqueous and
      ethanolic extracts were used in the following concentrations: 1.69; 3.37; 6.74;
      13.48 e 26.96 mg.mL(-1) and 4.17; 8.34; 16.68; 33.36 and 66.72 mg.mL(-1),
      respectively. The anthelmintic activity in vivo was determined by the
      administration of 10 mL.kg(-1) of the aqueous (50.1 mg.mL(-1)) and ethanolic
      (24.6 mg.mL(-1)) extracts during three consecutive days. Later the chickens were
      euthanized and necropsy was performed in order to count the remaining helminths.
      The data were analyzed by the Student-Newman-Keuls test. In the concentrations of
      13.48 and 26.96 mg.mL(-1), the aqueous extract demonstrated mortality of 46.67
      and 50%, respectively, there was a significative difference from the negative
      control (P < 0.05). The ethanolic extract presented statistical difference from
      the negative control (diluent) (P < 0.05) for the concentrations of 33.36 and
      66.72 mg.mL(-1), expressed by a mortality rate of 66.67 and 76.67%, respectively.
      In the in vivo test, the aqueous extract of noni fruit showed 27.08% of
      elimination, deferring statistically from the control group. There was no
      statistical difference between the ethanolic extract treatments and the control
      (P > 0.05). It follows that the anthelmintic activity of noni fruit test showed
      satisfactory results in vitro, there is a need for studies in higher
      concentrations in the in vivo test.

PMID- 20040207
TI  - [Grazing systems, rotenone and parasites control in crossbred calves: effect on
      live weight gain and on parasites burdens].
AB  - Practices for endo and ectoparasite control in beef cattle were evaluated in two
      independent experiments. First, the effects of rotenone on Rhipicephalus
      (Boophilus) microplus ticks were evaluated in vitro and in experimentally
      infected calves. In the second trial, the effects of grazing systems associated
      with endo and ectoparasite treatments on parasite burden and weight gain of
      naturally parasited animals were evaluated. Rotenone showed acaricide action on
      larvae and engorged ticks during in vitro tests and on larvae in experimentally
      infected calves. Three treatments with endectocide decreased (P < .05) the number
      of EPG and ticks and increased (P < .05) the weight gain in the dry season.
      Animals treated with only one application of levamisole showed EPG intermediate
      and different (P < .05) from the groups treated with endectocide (lower) and
      control (higher) in the dry season, but the weight gain obtained with this
      treatment did not differ from the control group. During the raining season the
      animals treated with fipronil were significantly less parasited by horn fly, tick
      and larvae of Dermatobia hominis and the group treated with rotenone were
      significantly less parasited by horn fly in relation to control. Animals under
      rotational grazing showed significantly higher EPG than those under continuous
      grazing. Three treatments with endectocide in the dry season plus three acaricide
      treatments with fipronil in the raining season reduced EPG, tick, and screw worm
      larva counts, and provided a significant increase (23 kg) of live weight gain in
      relation to untreated animals.

PMID- 20040208
TI  - [Plant extracts in control of Rhipicephalus (Boophilus) microplus (Canestrini,
      1887) (Acari: Ixodidae) in laboratory].
AB  - Plant extracts were studied to evaluate its efficiency in the control of
      Rhipicephalus (Boophilus) microplus (Canestrini, 1887) in laboratory. Engorged
      female ticks were collected from the cattle, kept in Petri dishes. Organic
      alcoholic extracts 2% (weight/volume) were used: seeds of Annona muricata L.
      (Annonaceae) (soursop); flowers of Syzygium malaccensis (L.) (Myrtaceae) (iamb),
      leaves of Cymbopogon citratus (DC.) Stapf (Poaceae) (holy grass), leaves of
      Azadirachta indica A. Juss (Meliaceae) (neem) and hexane extract 2%
      (weight/volume) of A. indica (seeds). The control groups consisted of untreated
      females and females treated with distilled water and sterile and
      dimethylsulfoxide (DMSO) a concentration of 1%. The extract of A. muricata (seed)
      had the highest mortality with acaricide activity and 100% efficacy followed by
      extracts of S. malaccensis (75 and 59.24%) and A. indica (65 and 38.49%). The
      seed extract of A. muricata reduced 100% larvae hatch.

PMID- 20040209
TI  - [Parasitic dynamics of gastrointestinal nematode infection in the periparturient
      period of beef cattle in the State of Para].
AB  - The experiment was conducted to investigate the dynamics of infection by
      gastrointestinal nematodes during the periparturition period in cows. One hundred
      and six beef cows were divided into two groups: G1 was formed by 42 cows of one
      and two parturitions, and G2 by 76 cows of three or more parturitions. From the
      120 days pre partum until the 90 days post partum, feces were collected for
      faecal egg counts (EPG) while blood was collected to determine the packed cell
      volume and hemoglobin levels of each animal, with monthly intervals. In the same
      intervals the body condition scores (BCS) were evaluated. The mean values +/-
      standard deviation of the EPG for G1 were equal to 19.4 +/- 42.9, and for G2 31.1
      +/- 68.0. No significant differences were observed between G1 and G2 in relation
      to EPG and hematological parameters, which remained within normal patterns for
      both groups. The two groups had higher counts of EPG in the post partum period
      than in the pre partum period, with averages of 32.5 +/- 55.5 and 51.5 +/- 84.8
      for groups G1 and G2, respectively. A significant difference (p < 0.05) in the
      parameters was observed when comparing the pre and post partum within each group
      studied resulting in declining values of blood and body score and an increase in
      EPG in the post partum. The results suggest that the cows may be more susceptible
      to infection by nematodes from giving birth up to 90 days post partum. However,
      adult cows, when well managed, are not an important factor in the epidemiology of
      gastrointestinal nematodes, even in the post partum period.

PMID- 20040211
TI  - [Comparison of different sampling traps for Dermanyssus gallinae (Acari:
      Dermanyssidae) (de Geer, 1778)].
AB  - This work aims to compare the performance of corrugated paper and "taquaril"
      bamboo (Phyllostachys sp.) straw traps for collecting (in sampling) Dermanyssus
      gallinae in a metal cages battery laying hens. The presence of eggs in the two
      trap models were compared using a Qui-square test and a proportion confidence
      interval test. Total daily values of mobile instars gathered in each type of trap
      were compared using the Wilcoxon's test. The amount of traps containing eggs was
      not different in neither of the traps (p < 0,05). The number of mobile instars
      sampled at every two days per trap model was different (p </= 0,01). Counting in
      the corrugated paper traps showed a Gauss distribution histogram and was superior
      to the values of the bamboo straw traps.

PMID- 20040210
TI  - [Salinomycin and semduramicin in different concentrations on the broilers
      eimeriosis control].
AB  - This study aimed to investigate the association of salinomycin and semduramicin,
      in different doses, against controlled mixed infection of Eimeria acervulina, E.
      maxima and E. tenella in broiler chickens. Eight hundred birds were divided into
      5 groups (T1: not medicated feed; T2: 30 ppm of salinomycin and 12.5 ppm of
      semduramicin; T3: 30 ppm of salinomycin and 15 ppm of semduramicin; T4: 40 ppm of
      salinomycin and 12,5 ppm of semduramicin and T5: 40 ppm of salinomycin and 15 ppm
      of semduramicin) and inoculated at 15 days of age with sporulated oocysts of E.
      acervulina, E. maxima and E. tenella in a mixed suspension, through the feed.
      Performance data and lesion scores were recorded. All treated groups showed
      statistically better cumulative weight gain at 21 days old. At 35 days old only
      the T3 group showed significant difference. Cumulative feed conversion showed
      statistical difference in the groups T4 and T5. The treatment T5 was more
      effective in the coccidiosis control of E. tenella. T3 and T5 achieved
      statistical differences in the average lesion scores of the three analyzed
      species. The association of salinomycin and semduramicin used in lower doses than
      the usual, showed to be an option in the coccidiosis control in this experiment.

PMID- 20040212
TI  - [Pasture contamination with infective larvae of gastrointestinal nematodes after
      grazing by sheep resistant or susceptible to parasitic infection].
AB  - The degree of contamination of herbage with third stage larvae of
      gastrointestinal nematodes was evaluated in paddocks grazed by resistant or
      susceptible ewes. The trial occurred from November 23, 2007 to July 22, 2008.
      Initially, fecal egg counts (FEC) were performed with individual samples of 130
      adult ewes of the Bergamacia breed. Of those animals, nine ewes with the highest
      FEC (susceptible group) and 10 with the lowest counts (resistant group) were
      selected and moved to separate paddocks. The resistant ewes presented lower FEC,
      higher values of packed cell volume, total plasma protein and blood eosinophils
      than the susceptible ewes. The weight was also higher in the resistant group.
      Haemonchus spp., Trichostrongylus spp. and Oesophagostomum spp. third stage
      larvae were recovered from pasture. In average, the amount of Haemonchus spp. and
      Trichostrongylus spp. third stage larvae in the pasture were 2.19 and 2.31 times,
      respectively, higher in the paddocks grazed by susceptible group in comparison
      with those grazed by the resistant animals. Therefore, the susceptible animals
      should be eliminated from the flock in order to reduce pasture contamination and
      optimize the prophylaxis of gastrointestinal nematode infections.

PMID- 20040213
TI  - [Ocurrence of Ornithonyssus bursa (Berlese, 1888) (Acari: Macronyssidae) on
      Megascops choliba (tropical screech-owl) and Pitangus sulphuratus (great
      kiskadee) nestlings in the Rio Grande do Sul State, Brazil].
AB  - The Center for Rehabilitation of Wildlife and Center for Selection of Wild Animal
      of the Federal University of Pelotas has attended two nestlings of Megascops
      choliba (tropical screech-owl) (Strigiformes - Strigidae) and two of Pitangus
      sulphuratus (great kiskadee) (Passeriformes - Tyrannidae) heavily parasitized by
      mites, in May 2005 and December 2006, respectively. The nestlings and the nest of
      P. sulphuratus were collected in the Pelotas urban area after severe storms. The
      mites were removed, clarified in lactofenol, permanently mounted in Hoyer's
      medium and identified as Ornithonyssus bursa (Acari - Macronyssidae). Megascops
      choliba and Pitangus sulphuratus are reported as host of Ornithonyssus bursa in
      Rio Grande do Sul State, Brazil.

PMID- 20040214
TI  - [Poecilancistrium caryophyllum (Diesing, 1850) (Cestoda, Trypanorhyncha),
      parasite of Macrodon ancylodon (Bloch & Schneider, 1801) from the Northern
      littoral of Brazil].
AB  - The aim of this research was to report the presence of Trypanorhyncha cestodes,
      their prevalence and mean intensity in the muscles musculature and abdominal
      serose in commercial fish processed in Belem, Para State. Fifty specimens of M.
      ancylodon were captured in the North Coast of Brazil. The musculature and
      adjacent abdominal serose of fish were analized in a "candling table" after
      filleted. Eight specimens were parasitized by plerocercoids of Poecilancistrium
      caryophyllum, with a prevalence of 16% and mean intensity of infection of one
      plerocercus per fish, varying from the unique site of infection was the
      musculature. The species P. caryophyllum is reported by the first time on M.
      ancylodon.The aim of this research was to report the presence of Trypanorhyncha
      cestodes, their prevalence and mean intensity in the muscles musculature and
      abdominal serose in commercial fish processed in Belem, Para State. Fifty
      specimens of M. ancylodon were captured in the North Coast of Brazil. The
      musculature and adjacent abdominal serose of fish were analized in a "candling
      table" after filleted. Eight specimens were parasitized by plerocercoids of
      Poecilancistrium caryophyllum, with a prevalence of 16% and mean intensity of
      infection of one plerocercus per fish, varying from the unique site of infection
      was the musculature. The species P. caryophyllum is reported by the first time on
      M. ancylodon.

PMID- 20040215
TI  - [Comparative efficacy of two topical formulations containing 10% fipronil on the
      control of Ctenocephalides felis felis on cats].
AB  - The goal of the present study was to evaluate the comparative efficacy of two
      topical formulations containing 10% fipronil on the control of Ctenocephalides
      felis felis on cats. The trial was performed at the Laboratory of Experimental
      Chemotherapy in Veterinary Parasitology from the Department of Animal
      Parasitology of the Institute of Veterinary of the Universidade Federal Rural do
      Rio de Janeiro. Eighteen mixed-breed cats were divided in three groups of six
      animals each. One group remained without treatment (control). The other groups
      received as treatment the two topical formulations, a commercial reference and
      the novel one, both containing 10% fipronil. Treated animals received 0.5 mL of
      product along their cervical region. Cats were infested on days - 2, +5, +12,
      +19, +26 and +33. Evaluations were made using the "comb test". The first one was
      undertaken 4 days after the initial infestation (day +2), and others 48 hours
      after following infestations (days +7, +14, +21, +28 and + 35). Both tested
      formulations had satisfactory efficacy until day + 35. No differences were
      observed comparing the efficacy levels between both formulations throughout the
      experimental period. The novel topical 10% fipronil formulation presented
      desirable efficacy on the control of C. f. felis on cats.

PMID- 20040216
TI  - Implementing the vision and moving forward.

PMID- 20040217
TI  - A shared worldview: mental health and public health at the crossroads.

PMID- 20040219
TI  - Primary care, public health, and mental health.

PMID- 20040218
TI  - Bridging mental health and public health.

PMID- 20040220
TI  - Ensuring the nation's mental health: the role of federal agencies.

PMID- 20040221
TI  - The role of state health departments in advancing a new mental health agenda.

PMID- 20040222
TI  - Familial risk for chronic disease and intent to share family history with a
      health care provider among urban Appalachian women, southwestern Ohio, 2007.
AB  - INTRODUCTION: Family history of certain chronic diseases is a risk factor for
      those diseases. We assessed demographic characteristics associated with familial
      risk for common diseases and whether familial risk was associated with intent to
      share family history with a health care provider among urban Appalachian women.
      METHODS: Urban Appalachian women (N = 88) with less than a college education
      participated in education sessions about family history in health promotion in
      southwest Ohio. Participants used My Family Health Portrait, electronically or on
      paper, to document their level of familial risk. Evaluations completed after each
      session gauged intent to share family history with a health care provider.
      RESULTS: Participants who used the paper version of My Family Health Portrait had
      lower odds of high familial risk for diabetes, heart disease, and stroke. Most
      participants (n = 62, 77%) reported that they intended to share their family
      history with a health care provider. Factors associated with intent to share
      family history included younger age, use of the electronic family history tool,
      and high familial risk of heart disease. CONCLUSION: The large proportion of
      women who intended to share family history with a health care provider may
      reflect the success of the educational component. Since familial risk for chronic
      disease is high among these urban Appalachian women, the need to share family
      history should continue to be promoted.

PMID- 20040223
TI  - Factors predicting glycemic control in middle-aged and older adults with type 2
      diabetes.
AB  - INTRODUCTION: Few studies have prospectively assessed the explanatory effects of
      demographics, clinical conditions, treatment modality, and general lifestyle
      behaviors on glycemic control in large heterogeneous samples of middle-aged and
      older adults with type 2 diabetes. We hierarchically examined these factors,
      focused especially on the effects of modifiable factors (ie, general lifestyle
      behaviors), and compared predictive patterns between middle-aged and older
      adults. METHODS: We used nationally representative data from the 1998 and 2000
      Health and Retirement Study (HRS) and the HRS 2003 Diabetes Study. We analyzed
      data from 379 middle-aged adults (aged 51-64 y) and 430 older adults (aged >or=65
      y) who self-reported having type 2 diabetes at baseline. RESULTS: Among middle
      aged adults, demographic factors and clinical conditions were the strongest
      predictors of hemoglobin A1c (HbA1c) levels. However, among older adults,
      treatment modality (diet only, oral medication, or insulin only or in combination
      with other regimens) significantly affected HbA1c levels. Lifestyle (physical
      activity, smoking, drinking, and body weight control), independent of the effects
      of demographics, clinical conditions, and treatment modality, significantly
      affected HbA1c levels. An increase of 1 healthy behavior was associated with a
      decrease in HbA1c levels of more than 1 percentage point. CONCLUSION: Our
      findings provide support for current diabetes guidelines that recommend a
      lifestyle regimen across the entire span of diabetes care and highlight the need
      to help both sociodemographically and clinically disadvantaged middle-aged adults
      with type 2 diabetes as well as older adults who exhibit poor adherence to
      medication recommendations to achieve better glycemic control.

PMID- 20040224
TI  - Health behaviors and quality of life of cancer survivors in Massachusetts, 2006:
      data use for comprehensive cancer control.
AB  - INTRODUCTION: Nearly 12 million cancer survivors are living in the United States.
      Few state-based studies have examined the health status and health-related
      quality of life (HRQOL) of this growing population. The objective of this study
      was to use Massachusetts Behavioral Risk Factor Surveillance System (BRFSS) data
      to describe cancer survivors' demographics, health behaviors, quality of life,
      use of preventive care services, and influenza vaccination rates. METHODS: The
      demographic characteristics of cancer survivors and respondents without cancer
      were estimated on the basis of responses to questions in the 2006 Massachusetts
      BRFSS. We used multivariate logistic regression to compare health behaviors,
      comorbidities, quality of life, and cancer screening and influenza vaccination
      rates for cancer survivors compared with respondents who did not have cancer.
      RESULTS: Cancer survivors and respondents who did not have cancer had similar
      rates of health behavioral risk factors including smoking, obesity, and physical
      activity. Rates of chronic disease (eg, heart disease, asthma) and disability
      were higher among cancer survivors. Cancer survivors reported higher rates of
      influenza vaccination and breast, colorectal, and cervical cancer screening than
      did respondents who did not have cancer. Survivors' self-reported health status
      and HRQOL (physical and mental health) improved as length of survivorship
      increased. CONCLUSION: This state-based survey allowed Massachusetts to assess
      health-related issues for resident cancer survivors. These findings will help
      state-based public health planners develop interventions to address the long-term
      physical and psychosocial consequences of cancer diagnosis and treatment.

PMID- 20040225
TI  - Optimized probability sampling of study sites to improve generalizability in a
      multisite intervention trial.
AB  - INTRODUCTION: Studies of type 2 translation, the adaption of evidence-based
      interventions to real-world settings, should include representative study sites
      and staff to improve external validity. Sites for such studies are, however,
      often selected by convenience sampling, which limits generalizability. We used an
      optimized probability sampling protocol to select an unbiased, representative
      sample of study sites to prepare for a randomized trial of a weight loss
      intervention. METHODS: We invited North Carolina health departments within 200
      miles of the research center to participate (N = 81). Of the 43 health
      departments that were eligible, 30 were interested in participating. To select a
      representative and feasible sample of 6 health departments that met inclusion
      criteria, we generated all combinations of 6 from the 30 health departments that
      were eligible and interested. From the subset of combinations that met inclusion
      criteria, we selected 1 at random. RESULTS: Of 593,775 possible combinations of 6
      counties, 15,177 (3%) met inclusion criteria. Sites in the selected subset were
      similar to all eligible sites in terms of health department characteristics and
      county demographics. CONCLUSION: Optimized probability sampling improved
      generalizability by ensuring an unbiased and representative sample of study
      sites.

PMID- 20040226
TI  - Prevalence of and susceptibility to cigarette smoking among female students aged
      13 to 15 years in Vietnam, 2007.
AB  - INTRODUCTION: Recent reports show a sharp increase in smoking rates among girls.
      We describe prevalence of cigarette smoking and susceptibility to cigarette
      smoking among female students aged 13 to 15 years in Vietnam and examine the
      associated factors. METHODS: We used data from female secondary school students
      aged 13 to 15 years (grades 8-10) from the 2007 Global Youth Tobacco Survey that
      was conducted in 9 provinces in Vietnam. We used multivariate logistic regression
      analysis to determine associations between independent variables with smoking
      status and susceptibility to smoking. RESULTS: Prevalence of cigarette smoking
      among girls was 1.2% (95% confidence interval [CI], 0.9-1.5), and 1.5% (95% CI,
      1.2-1.9) of girls were susceptible to smoking. Having friends who smoke was the
      strongest predictor of both smoking status and susceptibility to smoking.
      Attendance at school classes that described the harmful effects of smoking had
      significant effects in reducing cigarette smoking. Girls who were exposed to
      billboard cigarette advertising were more likely to be susceptible to smoking
      than were those who had not seen advertisements. CONCLUSION: Our findings
      highlight the need for pursuing school-based intervention programs in Vietnam and
      for countering tobacco advertising and marketing practices that target young
      women.

PMID- 20040227
TI  - The prevalence of multiple sclerosis in 3 US communities.
AB  - INTRODUCTION: We estimated the prevalence of multiple sclerosis (MS) in 3 large
      geographic areas in the southern, middle, and northern United States. METHODS:
      The primary data source was medical records from office visits to private
      neurologists' practices or to neurology departments in tertiary care facilities
      during a 3-year period. Additional data sources included patient advocacy groups,
      nursing homes, and general practitioners. RESULTS: Three-year US age-adjusted
      prevalence estimates for the study areas varied substantially. The prevalence was
      lowest (47.2 per 100,000 population) in the Texas study area (33 degrees 30'
      north latitude), intermediate (86.3 per 100,000 population) in the Missouri study
      area (39 degrees 07' north latitude), and highest (109.5 per 100,000 population)
      in the Ohio study area (41 degrees 24' north latitude). The geographic
      differences remained strong after age-adjustment to the world standard
      population. The inverse association between UV light exposure and MS prevalence
      estimates was consistent with this observed latitude gradient. In all 3 areas, MS
      prevalence was highest among women, people aged 40 to 59 years, and non
      Hispanics. CONCLUSION: These results provide necessary prevalence estimates for
      community cluster investigations and establish baseline estimates for future
      studies to evaluate temporal trends in disease prevalence.

PMID- 20040228
TI  - Ethnic and regional differences in prevalence and correlates of chronic diseases
      and risk factors in northern Canada.
AB  - INTRODUCTION: We investigated ethnic and geographic variations in major chronic
      diseases and risk factors in northern Canada, an area that is undergoing rapid
      changes in its social, cultural, and physical environments. METHODS: Self-report
      data were obtained from the population-based Canadian Community Health Survey in
      2000-2001 and 2005-2006 for Aboriginal and non-Aboriginal respondents from the 3
      regions of northern Canada: Yukon, Northwest Territories, and Nunavut. Crude
      prevalence estimates, adjusted odds ratios (AORs), and confidence intervals were
      calculated for multiple chronic diseases and risk factors. RESULTS: The
      percentage of Aboriginal respondents who reported having any chronic health
      condition increased between the 2 cycles of data collection, but did not change
      for non-Aboriginal respondents. AORs for heart disease, arthritis, and asthma
      varied by ethnicity or region. AORs for overweight, obesity, daily smoking,
      regular and binge drinking, and infrequent physical/leisure activity were also
      substantially different for Aboriginal and non-Aboriginal respondents or among
      respondents from the 3 northern regions. CONCLUSION: The changing profile of
      health in northern Canada suggests a need for action on health policy about the
      delivery of community-based primary prevention interventions and further research
      about the determinants of health and health care use.

PMID- 20040229
TI  - Lay representations of cancer prevention and early detection: associations with
      prevention behaviors.
AB  - INTRODUCTION: The Common Sense Model of illness representations posits that how
      people think about an illness affects how they try to prevent the illness. The
      purpose of this study was to determine whether prevention representations vary by
      cancer type (colon, lung, and skin cancer) and whether representations are
      associated with relevant behaviors. METHODS: We analyzed data from the Health
      Information National Trends Survey (HINTS 2005), a nationally representative
      survey of American adults (N = 5,586) conducted by telephone interview. RESULTS:
      Respondents reported that all 3 types of cancer can be prevented through healthy
      behaviors; however, fewer did so for colon cancer. More respondents reported
      screening as a prevention strategy for colon cancer than did so for lung or skin
      cancer. Representations were associated with colon cancer screening, smoking
      status, and sunscreen use. CONCLUSION: Representations of cancer were associated
      with relevant health behaviors, providing a target for health messages and
      interventions.

PMID- 20040230
TI  - Smoking status and cessation counseling practices among physicians, Guangxi,
      China, 2007.
AB  - INTRODUCTION: We examined Chinese physicians' smoking behavior, knowledge of
      smoking's health effects, and compliance with accepted cessation counseling
      practices. METHODS: We used a structured questionnaire adapted from the Global
      Health Professionals Survey of the World Health Organization to survey Chinese
      physicians based at 5 hospitals in Nanning, Guangxi Province, China. RESULTS: The
      response rate was 85% for a total of 673 completed questionnaires. Of the 673
      respondents, 73% were men, 42% were aged 30 years or younger, and 26% were
      smokers (men, 35%; women, 3%). Only 28% of the smokers were ready to quit
      immediately. A substantial proportion of physicians did not have adequate
      knowledge of smoking-related health hazards or favorable attitudes toward smoking
      cessation counseling. Asking patients whether they smoked and recording smoking
      status in the medical record were significantly associated with being female and
      being very well or somewhat prepared to counsel patients about smoking cessation.
      Advising patients to quit smoking was significantly associated with being female,
      being a nonsmoker, being very well or somewhat prepared to counsel patients about
      smoking cessation, and having read any smoking cessation guidelines. CONCLUSION:
      Our findings suggest that smoking is common among male Chinese physicians and
      that Chinese physicians have inadequate knowledge of smoking's health hazards and
      of how to help smokers quit. Physicians in China and their patients who smoke
      would benefit from widely accessible Chinese clinical practice guidelines on
      smoking cessation, better medical school education about the health risks of
      smoking, and government funding of cessation medications.

PMID- 20040231
TI  - Grading and reporting health and health disparities.
AB  - Report cards are widely used in health for drawing attention to performance
      indicators. We developed a state health report card with separate grades for
      health and health disparities to generate interest in and awareness of
      differences in health across different population subgroups and to identify
      opportunities to improve health. We established grading curves from data for all
      50 states for 2 outcomes (mortality and unhealthy days) and 4 life stages
      (infants, children and young adults, working-age adults, and older adults). We
      assigned grades for health within each life stage by sex, race/ethnicity,
      socioeconomics, and geography. We also assigned a health disparity grade to each
      life stage. Report cards can simplify complex information for lay audiences and
      garner media and policy maker attention. However, their development requires
      methodologic and value choices that may limit their interpretation.

PMID- 20040232
TI  - Public health surveillance for mental health.
AB  - Public health systems have relied on public health surveillance to plan health
      programs, and extensive surveillance systems exist for health behaviors and
      chronic disease. Mental health has used a separate data collection system that
      emphasizes measurement of disease prevalence and health care use. In recent
      years, efforts to integrate these systems have included adding chronic disease
      measures to the Collaborative Psychiatric Epidemiology Surveys and depression
      measures to the Behavioral Risk Factor Surveillance System; other data collection
      systems have been similarly enhanced. Ongoing challenges to integration include
      variations in interview protocols, use of different measures of behavior and
      disease, different interval reference periods, inclusion of substance abuse
      disorders, dichotomous vs continuous variables, and approaches to data
      collection. Future directions can address linking surveillance efforts more
      closely to the needs of state programs, increasing child health measurements in
      surveys, and improving knowledge dissemination from survey analyses.

PMID- 20040233
TI  - Simulating and evaluating local interventions to improve cardiovascular health.
AB  - Numerous local interventions for cardiovascular disease are available, but
      resources to deliver them are limited. Identifying the most effective
      interventions is challenging because cardiovascular risks develop through causal
      pathways and gradual accumulations that defy simple calculation. We created a
      simulation model for evaluating multiple approaches to preventing and managing
      cardiovascular risks. The model incorporates data from many sources to represent
      all US adults who have never had a cardiovascular event. It simulates
      trajectories for the leading direct and indirect risk factors from 1990 to 2040
      and evaluates 19 interventions. The main outcomes are first-time cardiovascular
      events and consequent deaths, as well as total consequence costs, which combine
      medical expenditures and productivity costs associated with cardiovascular events
      and risk factors. We used sensitivity analyses to examine the significance of
      uncertain parameters. A base case scenario shows that population turnover and
      aging strongly influence the future trajectories of several risk factors. At
      least 15 of 19 interventions are potentially cost saving and could reduce deaths
      from first cardiovascular events by approximately 20% and total consequence costs
      by 26%. Some interventions act quickly to reduce deaths, while others more
      gradually reduce costs related to risk factors. Although the model is still
      evolving, the simulated experiments reported here can inform policy and spending
      decisions.

PMID- 20040234
TI  - Evolving definitions of mental illness and wellness.
AB  - Understanding of the definitions of wellness and illness has changed from the mid
      20th century to modern times, moving from a diagnosis-focused to a person-focused
      definition of mental illnesses, and from an "absence of disease" model to one
      that stresses positive psychological function for mental health. Currently,
      wellness refers to the degree to which one feels positive and enthusiastic about
      oneself and life, whereas illness refers to the presence of disease. These
      definitions apply to physical as well as mental illness and wellness. In this
      article, we build on the essential concepts of wellness and illness, discuss how
      these definitions have changed over time, and discuss their importance in the
      context of health reform and health care reform. Health reform refers to efforts
      focused on health, such as health promotion and the development of positive well
      being. Health care reform refers to efforts focused on illness, such as treatment
      of disease and related rehabilitation efforts.

PMID- 20040235
TI  - The role of public health in addressing racial and ethnic disparities in mental
      health and mental illness.
AB  - Racial/ethnic minority populations are underserved in the American mental health
      care system. Disparity in treatment between whites and African Americans has
      increased substantially since the 1990s. Racial/ethnic minorities may be
      disproportionately affected by limited English proficiency, remote geographic
      settings, stigma, fragmented services, cost, comorbidity of mental illness and
      chronic diseases, cultural understanding of health care services, and
      incarceration. We present a model that illustrates how social determinants of
      health, interventions, and outcomes interact to affect mental health and mental
      illness. Public health approaches to these concerns include preventive strategies
      and federal agency collaborations that optimize the resilience of racial/ethnic
      minorities. We recommend strategies such as enhanced surveillance, research,
      evidence-based practice, and public policies that set standards for tracking and
      reducing disparities.

PMID- 20040236
TI  - Garnering partnerships to bridge gaps among mental health, health care, and
      public health.
AB  - Integrating mental health and public health chronic disease programs requires
      partnerships at all government levels. Four examples illustrate this approach: 1)
      a federal partnership to implement mental health and mental illness modules in
      the Behavioral Risk Factor Surveillance System; 2) a state partnership to improve
      diabetes health outcomes for people with mental illness; 3) a community-level
      example of a partnership with local aging and disability agencies to modify a
      home health service to reduce depression and improve quality of life among
      isolated, chronically ill seniors; and 4) a second community-level example of a
      partnership to promote depression screening and management and secure coverage in
      primary care settings. Integration of mental health and chronic disease public
      health programs is a challenging but essential and achievable task in protecting
      Americans' health.

PMID- 20040237
TI  - Developing and implementing the Massachusetts Comprehensive Cancer Control
      Coalition Survivorship Summit.
AB  - Cancer survivors face numerous medical and psychosocial challenges, which the
      medical and public health systems are ill-equipped to deal with. In May 2008, the
      Massachusetts Comprehensive Cancer Control Coalition conducted a Survivorship
      Summit to elicit input from cancer survivors and professionals on developing
      system-level action plans for cancer survivorship issues. We describe how health
      care and public health professionals can implement similar events. Our results
      suggest that a cancer survivorship summit can be a valuable tool for cancer
      coalitions and advocacy organizations in determining survivorship agendas and
      action plans.

PMID- 20040238
TI  - Choropleth map design for cancer incidence, part 1.
AB  - Choropleth maps are commonly used in cancer reports and community discussions
      about cancer rates. Cancer registries increasingly use geographic information
      system techniques. The Centers for Disease Control and Prevention's Division of
      Cancer Prevention and Control convened a Map Work Group to help guide application
      of geographic information systems mapping techniques and to promote choropleth
      mapping of data from central cancer registries supported by the National Program
      of Cancer Registries, especially for planning and evaluation of comprehensive
      cancer control programs. In this 2-part series in this issue of Preventing
      Chronic Disease, we answer frequently asked questions about choropleth map design
      to display cancer incidence data. We recommend that future initiatives consider
      more advanced mapping, spatial analysis, and spatial statistics techniques, and
      include usability testing with representatives of state and local programs and
      other cancer prevention partners.

PMID- 20040239
TI  - Choropleth map design for cancer incidence, part 2.
AB  - Choropleth maps are commonly used in cancer reports and community discussions
      about cancer rates. Cancer registries increasingly use geographic information
      system techniques. The Centers for Disease Control and Prevention's Division of
      Cancer Prevention and Control convened a Map Work Group to help guide application
      of geographic information system mapping techniques and to promote choropleth
      mapping of data from central cancer registries supported by the National Program
      of Cancer Registries, especially for comprehensive cancer control planning and
      evaluation purposes. In this 2-part series, we answer frequently asked questions
      about choropleth map design to display cancer incidence data. We recommend that
      future initiatives consider more advanced mapping, spatial analysis, and spatial
      statistics techniques and include usability testing with representatives of state
      and local programs and other cancer prevention partners.

PMID- 20040240
TI  - Worksite health promotion: principles, resources, and challenges.

PMID- 20040241
TI  - Bioanalytical inaccuracy: a threat to the integrity and efficiency of research.

PMID- 20040242
TI  - The contribution of hypersalience to the "jumping to conclusions" bias associated
      with delusions in schizophrenia.
AB  - BACKGROUND: Previous schizophrenia research involving the "beads task" has
      suggested an association between delusions and 2 reasoning biases: (1) "jumping
      to conclusions" (JTC), whereby early, resolute decisions are formed on the basis
      of little evidence and (2) over-adjustment of probability estimates following a
      single instance of disconfirmatory evidence. In the current study, we used a
      novel JTC-style paradigm to provide new information about a cognitive operation
      common to these 2 reasoning biases. METHODS: Using a task that required
      participants to rate the likelihood that a fisherman was catching a series of
      black or white fish from Lake A and not Lake B, and vice versa, we compared the
      responses of 4 groups (healthy, bipolar, nondelusional schizophrenia and
      delusional schizophrenia) when we manipulated 2 elements of the Bayesian formula:
      incoming data and prior odds. RESULTS: Regardless of our manipulations of the
      Bayesian formula, the delusional schizophrenia group gave significantly higher
      likelihood ratings for the lake that best matched the colour of the presented
      fish, but the ratings for the nonmatching lake did not differ from the other
      groups. LIMITATIONS: The limitations of this study include a small sample size
      for the group of severely delusional patients and a preponderance of men in the
      schizophrenia sample. CONCLUSION: Delusions in schizophrenia are associated with
      hypersalience of evidence-hypothesis matches but normal salience of nonmatches.
      When the colour of the incoming data is uniform (fish of only one colour), this
      manifests as JTC early in a series, and when the colour of incoming data varies
      (both black and white fish), this manifests as an overadjustment midseries. This
      account can provide a unifying explanation for delusion-associated performance
      patterns previously observed in the beads task in schizophrenia.

PMID- 20040244
TI  - Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental
      state for schizophrenia.
AB  - BACKGROUND: Accumulating evidence from postmortem and magnetic resonance imaging
      (MRI) studies suggests that abnormalities of medial temporal lobe structures are
      critically involved in the pathogenesis of schizophrenia. It is still unclear,
      however, whether certain abnormalities are already present in individuals at
      ultra high-risk (UHR) for transition into psychosis. Recent studies involving
      patients at UHR showed contradictory results for hippocampal volume, and only 1
      study reported that amygdalar volume was unchanged between healthy patients and
      those at UHR. Furthermore, no subregions of the hippocampus have been
      investigated in people at UHR. METHODS: We recruited 29 UHR patients, 23 first
      episode patients and 29 age- and sex-matched healthy controls. We measured
      hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually
      trace the regions of interest. The hippocampi were divided in 2 regions: head and
      corpus/tail. RESULTS: Patients at UHR had significantly smaller volumes of the
      hippocampus corpus and tail bilaterally, but not of the head, compared with
      healthy controls. Group differences for the right hippocampus corpus and tail
      volume remained significant after we controlled for whole brain volume and other
      covariates. We found that UHR patients who later developed psychosis had smaller
      right hippocampus corpus and tail volumes than did those who did not develop
      psychosis. First-episode patients had significantly smaller left amygdalar
      volumes than did healthy individuals or those at UHR. LIMITATIONS: Our study had
      a small sample size, and we were unable to control for the effects of medication.
      CONCLUSION: Our findings suggest that parts of the hippocampal-amygdalar complex
      are involved in the pathogenesis of schizophrenia. Reduction of hippocampus
      corpus and tail volumes may be indicative of the prodromal phase of schizophrenia
      and represent risk factors for transition into psychosis. Further investigations
      are needed to determine whether structural changes of the left amygdala play a
      role during transition from the prodromal phase to the first manifest episode of
      schizophrenia.

PMID- 20040243
TI  - Doxycycline inhibits proinflammatory cytokines but not acute cerebral cytogenesis
      after hypoxia-ischemia in neonatal rats.
AB  - BACKGROUND: Neonatal hypoxia-ischemia (HI) is a major cause of perinatal brain
      injury and is associated with a spectrum of neuropsychiatric disorders. Although
      very few treatment options are currently available, doxycycline (DOXY) has been
      reported to be neuroprotective in neontatal HI. Our objective was to investigate
      the effects of DOXY on neonatal brain development in normal and HI rat pups. We
      hypothesized that DOXY would inhibit microglial activation but that
      developmentally important processes, including cytogenesis and trophic responses,
      would not be impaired. METHODS: To investigate the putative neurodevelopmental
      consequences of DOXY administration in a clinically relevant animal model of HI,
      we performed a time-course analysis such that postnatal rat pups received DOXY
      (10mg/kg) or vehicle immediately before HI (n >or= 6). We then assessed
      cytogenesis, proinflammatory cytokines, brain-derived neurotrophic factor (BDNF)
      and matrix metalloproteinases regionally and longitudinally. RESULTS: We found
      that DOXY significantly inhibits neuroinflammation in the frontal cortex,
      striatum and hippocampus; decreases interleukin-1Beta (IL-1Beta) and tumour
      necrosis factor-alpha (TNF-alpha); and augments BDNF following HI. In addition,
      DOXY-treated pups have significantly fewer 2-bromo-5-deoxyuridine (BrdU)-positive
      cells in the subventricular zone 6 hours post-HI. However, DOXY does not
      persistently affect cytogenesis in the subventricular zone or dentate gyrus up to
      7 days post-HI. The BrdU-positive cells not expressing markers for mature neurons
      colabel with nestin, an intermediate filament protein typical of neuronal
      precursors. LIMITATIONS: Our study investigates "acute" neurodevelopment over the
      first 7 days of life after HI injury. Further long-term investigations into
      adulthood are underway. CONCLUSION: Taken together, our results suggest the
      putative clinical potential of DOXY in the management of neonatal cerebral HI
      injury.

PMID- 20040245
TI  - Differential patterns of initial and sustained responses in amygdala and cortical
      regions to emotional stimuli in schizophrenia patients and healthy participants.
AB  - BACKGROUND: We sought to investigate the altered brain responses to emotional
      stimuli in patients with schizophrenia. METHODS: We analyzed data from 14
      patients with schizophrenia and 14 healthy controls who performed an emotional
      face matching task. We evaluated brain activity and connectivity in the amygdala
      and cortical regions during the initial (first 21 seconds of each stimulation
      block) and sustained (last 21 seconds) stages of an emotional processing task,
      and we determined changes in amygdala activity across the emotional processing
      task. RESULTS: The patients with schizophrenia showed similar amygdala activation
      to the controls during the initial stage of processing, but their activation
      decreased during the sustained stage. The controls showed increasing amygdala
      activity across the emotional blocks, whereas activity progressively decreased in
      the schizophrenia group. The patients with schizophrenia showed increased
      cortical activity and interconnectivity in the medial frontal and inferior
      parietal cortex in the initial stage of emotional processing.There was increased
      activity in the superior temporal cortex and greater connectivity with the
      inferior parietal cortex in the sustained stage. Performance accuracy was lower
      in the schizophrenia group in the first part of the block, while their reaction
      time was longer in the latter part of the block. LIMITATIONS: It was not possible
      to specify the moment at which the switch in amygdala response occurred.
      CONCLUSION: Our findings suggest that patients with schizophrenia have an initial
      automatic emotional response but that they need to switch to a compensatory
      cognitive strategy to solve the task.

PMID- 20040246
TI  - Social cognition mediates illness-related and cognitive influences on social
      function in patients with schizophrenia-spectrum disorders.
AB  - BACKGROUND: Although cognition has been studied extensively among patients with
      schizophrenia, social cognition has only recently emerged as an area of interest.
      The objective of the current study was to use structural equation modelling to
      test the hypothesis that the relation between cognitive performance and social
      function is mediated by patients' social cognitive abilities. METHODS: We
      assessed participants who met criteria for a schizophrenia-spectrum disorder,
      with equal distribution among first- and multi-episode participants, and
      nonpsychiatric controls on a range of measures within each of the domains of
      cognition, social cognition and social function. RESULTS: Using structural
      equation modelling, we derived a model that explained 79.7% of the variance in
      social function and demonstrated that the link between cognition and social
      function was fully mediated by social cognition. LIMITATIONS: A limitation of
      this study is that the measures contributing to the structural equation modelling
      analysis were obtained at the same point in time. Thus, the temporal order of
      causation suggested by Model 2 remains theoretically specified. CONCLUSION: This
      study provides some first steps in understanding the complex relation between
      cognition and social function. Such a relation has potential implications for the
      design of remediation strategies.

PMID- 20040247
TI  - Structural abnormality of the substantia nigra in children with attention-deficit
      hyperactivity disorder.
AB  - BACKGROUND: Structural abnormality of the substantia nigra can be detected by
      transcranial sonography in neuropsychiatric disorders such as Parkinson disease
      and restless legs syndrome. We investigated echogenicity of the substantia nigra
      as a potential structural marker for dysfunction of the nigrostriatal dopamine
      system in children with attention-deficit hyperactivity disorder (ADHD). METHODS:
      We used a blinded design and determined echogenicity of the substantia nigra by
      use of transcranial sonography in 22 children with ADHD and 22 healthy controls
      matched for age and sex. RESULTS: The echogenic substantia nigra area was
      significantly larger in ADHD patients than in healthy controls (F(1,42) = 9.298,
      p = 0.004, effect size = 0.92). We found no effects of age or sex. LIMITATIONS:
      Owing to a lack of dimensional assessment, we could not analyze the correlation
      between echogenicity and clinical symptoms. CONCLUSION: Our results support the
      hypothesis that the nigrostriatal dopaminergic system is abnormal in children
      with ADHD.

PMID- 20040248
TI  - Circulating plasmalogen levels and Alzheimer Disease Assessment Scale-Cognitive
      scores in Alzheimer patients.
AB  - BACKGROUND: Plasmalogens, which are key structural phospholipids in brain
      membranes, are decreased in the brain and serum of patients with Alzheimer
      disease (AD). We performed this pilot study to evaluate the relation between the
      levels of circulating plasmalogens and Alzheimer Disease Assessment Scale
      Cognitive (ADAS-Cog) scores in patients with AD. METHODS: We evaluated
      participants' ADAS-Cog scores and serum plasmalogen levels. For the 40 included
      AD patients with an ADAS-Cog score between 20 and 46, were tested their ADAS-Cog
      score 1 year later. The levels of docosahexaenoic acid plasmalogen were measured
      by use of liquid chromatography-tandem mass spectrometry. RESULTS: We found that
      the ADAS-Cog score increased significantly in AD patients with circulating
      plasmalogen levels that were <or= 75% of that of age-matched controls at entry
      into the study. There was no change in score among participants with normal serum
      plasmalogen levels at baseline (> 75%). LIMITATIONS: This was a pilot study with
      40 patients, and the results require validation in a larger population.
      CONCLUSION: Our study demonstrates that decreased levels of plasmalogen
      precursors in the central nervous system correlate with functional decline (as
      measured by ADAS-Cog scores) in AD patients. The use of both ADAS-Cog and serum
      plasmalogen data may be a more accurate way of predicting cognitive decline in AD
      patients, and may be used to decrease the risk of including patients with no
      cognitive decline in the placebo arm of a drug trial.

PMID- 20040250
TI  - Treatment of bipolar disorder with comorbid migraine.

PMID- 20040251
TI  - Symmetrical bilateral Becker melanosis: A rare presentation.
AB  - Becker melanosis, also known as Becker nevus, is a relatively common cutaneous
      hamartoma. The condition is classically characterized by a unilateral,
      hyperpigmented patch with varying degrees of hypertrichosis on a peripubertal
      individual. As Becker nevi are generally singular in a given individual, there
      are very few reported cases of multiple or bilateral lesions. We herein report a
      rare case of bilateral, symmetrical, non-syndromic Becker melanosis and we
      discuss possible pathogenesis and current treatment options.

PMID- 20040252
TI  - Acquired dermal melanocytosis of the hand at the site of treated psoriasis.
AB  - Dermal melanocytosis is a benign phenomenon most commonly noted in people with
      darkly pigmented skin. Multiple entities with dermal melanocytosis are described,
      including Mongolian spot, nevus of Ota, nevus of Ito, nevus of Hori, and acquired
      dermal melanocytosis. We report a case of acquired dermal melanocytosis occurring
      in a 42-year-old Hispanic man with psoriasis treated with infliximab for 9
      months. The patient presented with an isolated pigmented patch on his left dorsal
      hand. Histopathologic examination of the skin revealed numerous dendritic,
      heavily pigmented melanocytes in the papillary and upper reticular dermis. We
      review the literature and discuss the pathogenesis of acquired dermal
      melanocytosis.

PMID- 20040253
TI  - Granuloma faciale: Case report and review.
AB  - Granuloma faciale (GF) is a rare benign chronic inflammatory dermatosis usually
      appearing only on the face. The lesions of GF typically present as single,
      asymptomatic, erythematous, non-changing nodules or plaques. We present an
      illustrative case of GF and briefly review available treatment options.

PMID- 20040254
TI  - Interferon induced sarcoidosis with cutaneous involvement along lines of venous
      drainage in a former intravenous drug user.

PMID- 20040255
TI  - Two pediatric cases of Blau syndrome.

PMID- 20040256
TI  - A case of Kaposi sarcoma mimicking nephrogenic systemic fibrosis.
AB  - Kaposi sarcoma is a neoplasm commonly seen in HIV patients. Cutaneous lesions may
      vary in presentation between patients. In AIDS-associated Kaposi sarcoma, small
      red papules or nodules initially present on the face, especially on the nose, and
      the trunk, that then rapidly spread to other areas. We present an unusual case of
      AIDS-associated Kaposi sarcoma mimicking nephrogenic systemic fibrosis.

PMID- 20040257
TI  - Clinical pearl for the diagnosis of Hansen disease.

PMID- 20040258
TI  - Fluoroquinolone-induced generalized fixed drug eruption.

PMID- 20040259
TI  - Primary cutaneous CD30+ large-cell lymphoma presenting as a scrotal plaque.
AB  - Primary cutaneous CD30+ large-cell lymphoma (CD30+ LCL) is a rare subtype of
      cutaneous T cell lymphoma. We report a patient with a one-year history of an
      enlarging scrotal plaque. Skin biopsy stained positive for CD30, and after
      thorough systemic evaluation, a diagnosis of primary cutaneous CD30+ LCL was
      made. Most commonly CD30+ LCL presents on the extremities and trunk. We present
      the first case to our knowledge of a patient initially presenting with a solitary
      scrotal nodule. When primary cutaneous CD30+ LCL is suspected, it is important to
      conduct a thorough systemic evaluation for systemic LCL and immunohistological
      studies for CD30- types. Ruling these conditions out will prevent unnecessarily
      aggressive treatment for primary cutaneous CD30+ LCL, an indolent disease with a
      favorable prognosis.

PMID- 20040260
TI  - Vogt-Koyanagi-Harada syndrome: Association with alopecia areata.
AB  - Vogt-Koyanagi-Harada (VKH) syndrome is an inflammatory condition characterized by
      bilateral uveitis, vitiligo, poliosis, alopecia, and dysacousia. The syndrome
      results from a T cell mediated autoimmune attack on melanocytes in genetically
      susceptible individuals. We present a case of VKH syndrome and propose that the
      alopecia and poliosis described in the original reports by ophthalmologists could
      instead be alopecia areata with re-growth of white hair.

PMID- 20040261
TI  - Transfer contact dermatitis caused by rosin use in bowling.
AB  - The diagnosis of allergic contact dermatitis due to colophony may be challenging
      as this allergen is found in a number of products and used in a variety of
      settings. Diagnosis becomes more difficult when the distribution of dermatitis
      does not coincide with typical patterns of use of the allergen. We present a case
      of transfer contact dermatitis of the face due to rosin use in bowling.

PMID- 20040262
TI  - Treatment of necrobiosis lipoidica with etanercept and adalimumab.

PMID- 20040263
TI  - Treatment of pityriasis amiantacea with infliximab.

PMID- 20040264
TI  - Two cases of photocontact allergy to the new sun filter octocrylene.
AB  - We report two cases of photocontact allergy to a cinnamate sun filter,
      octocrylene. In the last few years octocrylene has been broadly used in the
      manufacturing of many cosmetics and UV filters, hence the importance of
      octocrylene as an emerging cause of contact and photocontact allergy.

PMID- 20040265
TI  - Persistent cutaneous hyperpigmentation due to hydroxychloroquinone one year after
      therapy discontinuation.
AB  - Hydroxychloroquine (HCQ) was initially indicated for the treatment of malaria,
      but more recently its anti-inflammatory and immune modulating properties have
      been utilized for treatment of multiple dermatologic and rheumatologic diseases.
      Mucocutaneous bluish-gray dyschromia is a rare side effect with HCQ and little
      information exists regarding its duration after drug discontinuation. The few
      existing case reports primarily describe small focal areas of discoloration. More
      extensive dyschromia has very rarely been reported with HCQ. We report a case of
      HCQ induced dyschromia diffusely involving the extremities, with minimal
      resolution one year after treatment discontinuation.

PMID- 20040266
TI  - Promises and drawbacks of targeting cell cycle kinases in cancer.
AB  - The loss of ability in controlling cell cycle leads to aberrant cell growth and
      is a hallmark of cancer cells. Cell cycle regulation and progression mainly rely
      on protein phosphorylation events, therefore cell cycle kinases have long been
      viewed as potential targets for anticancer strategies. Consistently, cell cycle
      kinases are often dysregulated in different types of human cancer. Despite years
      of research and attempts directed at inhibiting cell cycle kinases, none of these
      approaches has been successfully translated to the clinic to halt tumorigenesis.
      Here, we review several currently pursued strategies and highlight both current
      challenges and some recent findings, which might help to develop new, better
      conceived therapeutic approaches based on cell-cycle kinase inhibition.

PMID- 20040267
TI  - Screening for EGFR mutations in lung cancer.
AB  - Certain mutations in the epidermal growth factor receptor (EGFR) gene confer
      hypersensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in
      patients with advanced non-small cell lung cancer. Large-scale screening for EGFR
      mutations in such patients is feasible for predicting response to TKIs and thus
      guiding treatment.

PMID- 20040268
TI  - Therapeutic selectivity and the multi-node drug target.
AB  - Drug combinations are an increasingly favored strategy for increasing therapeutic
      windows for potential drugs, but enthusiasm for this approach is tempered by
      concerns that therapeutic synergy will too often be mirrored by synergistic
      toxicity. Here we review our recent experimental results and numerical
      simulations that establish the context-specificity of synergistic combinations.
      Thus systematic testing of chemical combinations in cell-based disease models can
      preferentially discover synergies with beneficial therapeutic selectivity. For an
      anti-inflammatory combination, we demonstrate how such selective synergy is
      achieved through differential expression of its targets in cells associated with
      therapeutic and toxic effects, and validate the combination's therapeutic
      relevance in animals. The narrower context specificity of synergistic
      combinations creates many new opportunities for such therapeutically relevant
      selectivity, and reinforces the realization that the most useful paradigm for a
      drug target is often a set of biomolecules that cooperate to produce a
      therapeutic response with reduced side effects.

PMID- 20040269
TI  - Cognitive functioning in Tourette syndrome.
AB  - Tourette Syndrome (TS) is characterized by tics, which are thought to reflect
      striatal dysfunction. Changes in functioning of the striatum in TS could lead to
      dysfunction in frontostriatal pathways involving cortical regions such as the
      dorsolateral prefrontal and anterior cingulate cortex. This in turn could result
      in deficits in specific cognitive processes and impairment on particular
      cognitive tasks. The aim of this review is to summarize the major findings of key
      studies of cognitive functioning in TS. The limitations and neurological
      implications of the reported findings are also discussed. Although the
      methodological limitations associated with many studies compel further
      investigation, tentative conclusions may be drawn from the available literature.
      While co-morbidities such as attention deficit-hyperactivity disorder (ADHD) may
      be associated with more significant executive dysfunction, we can conclude that
      patients without co-morbidities exhibit milder deficits in attention and
      inhibition-related processes. These cognitive difficulties are likely to reflect
      dysfunction with frontostriatal pathways involving the anterior cingulate
      circuit.

PMID- 20040270
TI  - Oral anticoagulation with Factor Xa and thrombin inhibitors: Is there an
      alternative to warfarin?
AB  - Vitamin K antagonists (VKA), such as warfarin, have been the only available oral
      anticoagulants despite their many limitations. The greatest medical need is to
      find a replacement for warfarin for long-term therapy, particularly for stroke
      prevention in atrial fibrillation (AF) patients. Emerging oral anticoagulants are
      free from many of warfarin's drawbacks and may offer a convenient alternative.
      Drugs in advanced development target factor Xa (rivaroxaban, apixaban) or
      thrombin (dabigatran etexilate). Recently, the RE-LY phase III study found
      dabigatran etexilate was an effective and convenient alternative to warfarin in
      stroke prevention for AF patients. Within the next two years, similar studies
      comparing rivaroxaban and apixaban versus warfarin in AF patients will become
      available. This paper reviews warfarin's limitations, discusses the
      pharmacokinetics of emerging anticoagulants in advanced development, and
      summarizes trials with an emphasis on head-to-head studies comparing novel
      anticoagulants to warfarin.

PMID- 20040271
TI  - Second and third line treatment in advanced non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths
      worldwide. About 50% of the patients present locally advanced or metastatic
      disease at the time of diagnosis. First line therapy usually consists of a
      combination of cisplatin or carboplatin with a third-generation agent
      (paclitaxel, docetaxel, gemcitabine, or vinorelbine) that results in less than 5%
      5-year survival (Goldstraw et al., 2007). Recently a different approach based on
      histological subtype has been introduced in the first line treatment of NSCLC: in
      the non-squamous histotypes, cisplatin plus pemetrexed, compared to the cisplatin
      plus gemcitabine combination, showed a better outcome, leading to its
      introduction in the first line treatment setting. In recent years advances in the
      second and third line treatments have led to a prognostic improvement. Two
      cytotoxic agents, docetaxel and pemetrexed, are approved as NSCLC second line
      treatment, and a new class of drugs against specific molecular targets --
      tyrosine Kinase inhibitors (TKI) -- has emerged as an alternative to conventional
      treatment. Many trials are ongoing to assess the activity of new drugs, alone or
      in combination with other agents, or new combinations of third-generation
      chemotherapeutic agents.

PMID- 20040272
TI  - Artificial antigen presenting cells that express prevalent HLA alleles: A step
      towards the broad application of antigen-specific adoptive cell therapies.
AB  - The artificial antigen-presenting cells (AAPCs) described in this review were
      generated to facilitate the production of virus-specific T-cells for the
      treatment of infections in patients after bone marrow transplant. These AAPCs
      consist of murine 3T3 cells genetically modified to express critical human
      molecules needed for T-cell stimulation, such as the co-stimulatory molecules
      B7.1, ICAM-1, and LFA-3 and one of a series of 6 common HLA class I alleles. When
      T-cells were sensitized against cytomegalovirus (CMV) using AAPCs that express a
      shared HLA allele or using autologous antigen-presenting cells (APCs) loaded with
      the CMVpp65 antigen, they were activated and expanded to become HLA-restricted
      CMVpp65-specific T-cells. These T-cells demonstrated functional activity in vitro
      against CMV by producing IFN-gamma and inducing CMVpp65-specific cytotoxicity. T
      cells sensitized with AAPCs recognized antigenic epitopes presented by each HLA
      allele known to be immunogenic in Man. Sensitization with AAPCs also permitted
      expansion of IFN-gamma+ cytotoxic T-cells against subdominant epitopes that were
      not effectively recognized by T-cells sensitized with autologous APCs. This panel
      of AAPCs provides a source of immediately accessible, standardizable, and
      replenishable "off the shelf" cellular reagents with the potential to make
      adoptive immunotherapy widely available for the treatment of lethal infections,
      cancer, and autoimmune diseases.

PMID- 20040273
TI  - Immune modulation of blood-derived stem cell as a comprehensive tool for treating
      type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which the patient's immune
      system recognizes their pancreatic islet insulin-producing cells and destroys
      them. To cure T1D in a comprehensive manner, not only must the islet cells be
      replaced, the patient's immune system must also be properly regulated mostly in
      the form of suppression. Blood-derived new stem cells have shown promise in both
      aspects of this treatment.

PMID- 20040274
TI  - Programmed cell death and apoptosis in aging and life span regulation.
AB  - Increasing evidence suggests an important role for programmed cell death (PCD)
      pathways in aging phenotypes across species. PCD is critical to the homeostasis
      of tissues maintained by cell division, for example, the blood and the lining of
      the gut. During aging, accumulated cellular damage and non-optimal systemic
      signaling can cause too little cell death (hyperproliferation and cancer), or too
      much cell death (tissue atrophy and ectopic cell death), thereby limiting tissue
      function and life span. For these reasons PCD pathways are promising targets for
      interventions in aging and aging-related diseases: reactivation of PCD may be
      beneficial in clearing cancerous and senescent cells, whereas inhibiting PCD may
      help prevent muscle atrophy and nervous system degeneration.

PMID- 20040275
TI  - A small step towards personalized medicine for non-small cell lung cancer.
AB  - Treatment outcome for advanced-stage non-small cell lung cancer (NSCLC) is
      limited by empiric administration of cytotoxic chemotherapy. Recent advances in
      molecular genomics have revolutionized cancer management and, specifically,
      epidermal growth factor receptor (EGFR) mutation has become a potent biomarker
      for lung cancer, which predicts tumor response to and prolonged duration of
      disease control by EGFR tyrosine kinase inhibitors (TKI). The Iressa Pan-Asia
      Study (IPASS) is a randomized phase III study comparing gefitinib (EGFR TKI) with
      paclitaxel/carboplatin (standard chemotherapy) in Asian non-/light smokers with
      adenocarcinoma. Progression-free survival (PFS) in EGFR mutation-positive
      patients was longer with gefitinib than with chemotherapy (hazard ratio [HR],
      0.48; 95% confidence interval [CI], 0.36-0.64; p<0.0001); in EGFR mutation
      negative patients, PFS was longer with chemotherapy than with gefitinib (HR 2.85;
      95% CI 2.05-3.98; p<0.0001). The findings are confirmed by one single-arm study
      and three other randomized studies. It has become clear that personalized
      medicine for NSCLC is feasible. This small step towards personalized medicine
      represents a paradigm shift in the management of NSCLC.

PMID- 20040276
TI  - What do we know about chronic tension-type headache?
AB  - In the past few years there has been an increasing body of knowledge about
      etiological mechanisms of chronic tension type headache (CTTH), permitting a
      better understanding of this syndrome. It seems that CTTH diagnostic criteria
      should be modified to improve its differential diagnosis against migraine, since
      CTTH is a syndrome of "featureless" headaches characterized by nothing but pain
      in the head. It has been demonstrated that pressure pain hypersensitivity and
      pericranial muscle tenderness are both consequence and not causative factors of
      CTTH. An updated pain model has suggested that CTTH can be explained by referred
      pain from trigger points (TrPs) in the cranio-cervical muscles, mediated through
      the spinal cord and the trigeminal nerve nucleus caudalis. Different therapeutic
      strategies (pharmacological and non-pharmacological) are generally used for the
      management of these patients. CTTH is generally treated with non-steroidal anti
      inflammatory drugs (NSAIDs), tricyclic antidepressants, and physical therapy,
      although the therapeutic efficacy of these approaches is controversial.

PMID- 20040277
TI  - Role of platelet-derived microparticles in angiogenesis and tumor progression.
AB  - Platelets are key players in hemostasis, but are also involved in fundamental
      processes of vascular biology such as angiogenesis, tissue regeneration, and
      tumor metastasis. Microparticles (MP) are small plasma membrane vesicles shed
      from cells upon their activation or apoptosis. Platelet-derived microparticles
      (PMP) constitute the majority of the pool of MP circulating in the blood. In this
      review we will summarize some possible roles of PMP other than participation in
      blood coagulation. PMP can express and transfer functional receptors from
      platelet membranes, increase expression of adhesion molecules on cells, stimulate
      the release of cytokines, activate intracellular signaling pathways, alter
      vascular reactivity, induce angiogenesis, and are involved in cancer metastasis.
      The role of PMP in cancer development is unknown but a high PMP level is highly
      correlated with aggressive tumors and a poor clinical outcome. It has been
      reported that PMP can stimulate proliferation and adhesion of cancer cells. Given
      their documented association with pathological conditions, PMP may serve as
      biomarkers for disease status or as a possible new target for anti-platelet drugs
      to treat cancer or inflammation. On the other hand, local PMP application may be
      found useful for developing novel therapeutic strategies targeting angiogenesis
      related conditions.

PMID- 20040278
TI  - Frontiers in platelet inhibition.
AB  - Anti-platelet drugs play a key role in cardiovascular medicine since the
      introduction of aspirin as an anti-thrombotic agent some 50 years ago. After many
      years of a "monopoly" of aspirin, ADP receptor P2Y12 inhibitors were introduced
      with a significant improvement in clinical outcome. Nowadays dual anti-platelet
      therapy is the common practice for both acute events and secondary prevention in
      selected groups of patients. The improved efficacy of multiple drug therapy is
      associated with an increased risk of bleeding, which raises the issue of the
      dosing of these drugs. Recently, numerous studies have reported a variable
      laboratory response to aspirin and clopidogrel, which correlates with clinical
      outcome. Several mechanisms for causing this variable response have been
      proposed, including genetic variability, disease burden, and others. A major
      obstacle in this field is the lack of a standardized method for testing these
      responses. New drugs are currently under different stages of development,
      including new P2Y12 receptors inhibitors, thrombaxane receptor blockers, direct
      thrombin inhibitors, and inhibitors for other signaling pathways including oral
      GPIIbIIIa inhibitors. Thus anti-platelet therapy is currently under intensive
      developments toward multiple drug therapy and personal dose adjustment, which may
      improve clinical outcome.

PMID- 20040279
TI  - Glycomimetic drugs--a new source of therapeutic opportunities.
AB  - Carbohydrates are ubiquitous and represent the most abundant class of molecules
      in nature. All cell surfaces are coated with complex carbohydrates where they act
      as recognition molecules for other cells, functional molecules, and pathogens.
      Consequently, they are involved in disease indications as diverse as
      inflammation, cancer, and infectious disease. In general, native carbohydrates
      lack the properties necessary for efficacious drugs and historically have not
      been successful candidates to capitalize on these applications. Understanding the
      bioactive conformation and molecular interactions of functional carbohydrates,
      however, allows the rational design of small molecule glycomimetics that exhibit
      improved drug-like properties such as increased affinity, serum half-life,
      stability, and bioavailability. Recent advances in analytical techniques (i.e.,
      NMR, x-ray crystallization), molecular modeling, and synthetic organic chemistry
      allow the design of potent glycomimetic compounds, which opens the door to a new
      class of therapeutic drugs to target molecular mechanisms that can address many
      of the current unmet needs in the treatment of disease.

PMID- 20040280
TI  - The road to therapeutic RNA interference (RNAi): Tackling the 800 pound siRNA
      delivery gorilla.
AB  - If those of us privileged enough to have the opportunity to work towards curing
      human diseases had the power to design the ideal therapeutic molecule, the
      question would be what selection criteria would we choose? Arguably, at the top
      of the list would be four mandatory properties: specificity, potency,
      tolerability, and universality. So it should come as no surprise the momentum
      associated with the field of small interfering RNA (siRNA)-induced RNA
      Interference (RNAi) therapeutics has gained strength, as these molecules have
      shown exceptional promise in fulfilling all of these requirements. Unfortunately,
      siRNAs are too large, too charged, and too rigid to passively diffuse across the
      cellular membrane and thereby require a delivery system to enter cells. Thus,
      since its conception of working in human cells, siRNA delivery remains The 800
      Pound Gorilla in the room. The main complication yet to overcome is engineering
      delivery systems that are safe and efficient in systemically delivering siRNA
      molecules to the diseased tissue and across the cellular membrane of target
      cells. Currently, encapsulating the siRNA in nanoparticle and liposomal systems
      has risen to become the standard of delivery approaches. While generally speaking
      these delivery platforms offer significant advancements, our laboratory is
      committed to generating alternative siRNA delivery technologies that avoid
      nanoparticle packaging and allow siRNA molecules to be delivered as single,
      soluble entities. This brief review discusses the first of these technologies, a
      Peptide Transduction Domain-dsRNA Binding Domain (PTD-DRBD) fusion protein that
      avidly binds to the siRNA backbone to mask the negative charge and uses the PTD
      for macromolecular cellular delivery.

PMID- 20040305
TI  - Eighth International Symposium on Lysosomal Storage Diseases.

PMID- 20040306
TI  - Disease pathogenesis--basic science.

PMID- 20040307
TI  - The endosomal network.
AB  - Endocytosis is the process by which extracellular molecules are captured by the
      cell surface membrane and then taken up into the cell. Once inside the cell, the
      internalized material is delivered to its final destination via a complex system
      of organelles, termed the endosomal network. These heterogeneous structures play
      a key role in the delivery of extracellular and cellular material towards the
      lysosome for macromolecular degradation. The internalization of mannose-6
      phosphate receptors at the cell surface, and their subsequent delivery to the
      late endosome, is the basis of enzyme replacement therapy in patients with
      lysosomal storage diseases (LSDs). This review describes the characteristics of
      the endosomal network and discusses how disturbances in vesicular trafficking or
      intracellular signaling may be important in the pathology of LSDs.

PMID- 20040308
TI  - Intracellular trafficking of lysosomal proteins and lysosomes.
AB  - In the synthesis and trafficking of precursors of most lysosomal matrix proteins,
      the stages necessary for lysosomal delivery include the addition of
      phosphorylated mannose-rich oligosaccharides, binding of the modified proteins to
      receptors, their segregation from the secretory pathways and delivery to the
      endosomal pathway. Targeting of both internally synthesized and externally
      provided enzymes (as in enzyme replacement therapy) to endosomes is executed by a
      complex machinery of membrane and cytosolic proteins. Recently, the homotypic
      fusion and vacuolar protein sorting (HOPS) complex has been identified in
      lysosomes from human cells. This complex is likely to play an important role in
      the exchange of enzymes between endosomal and lysosomal compartments. The present
      review describes the interactions and functions of proteins that participate in
      delivering lysosomal proteins to different lysosomal compartments. In summary,
      lysosomal trafficking depends on the recognition of many structural signals. It
      delivers soluble and membrane proteins, and can be exploited for therapeutic
      substitution of missing enzymes.

PMID- 20040309
TI  - Disease pathogenesis explained by basic science: lysosomal storage diseases as
      autophagocytic disorders.
AB  - Lysosomal storage diseases (LSDs) are characterized by intra-lysosomal
      accumulation of undegraded metabolites due to the defective activity of lysosomal
      enzymes. There is a paucity of data, however, relating to the mechanisms that
      link this accumulation with disease pathology. Several LSDs can be attributed to
      deficiencies in the activity of sulfatase enzymes. The gene responsible for the
      post-translational modification that activates sulfatases, sulfatase modifying
      factor 1 (SUMF1), is defective in the rare autosomal recessive disorder multiple
      sulfatase deficiency (MSD). A mouse model of MSD (Sumf1 knockout mouse) exhibits
      a similar phenotype to patients with MSD, with marked lysosomal storage of
      undegraded metabolites, and increased expression of inflammatory markers and
      apoptotic markers. Investigation of disease pathology in mouse models of two LSDs
      (MSD and mucopolysaccharidosis (MPS) Type IIIA) has revealed an increased number
      of autophagosomes in these animals compared with wild-type mice. This appears to
      result from impaired autophagosome-lysosome fusion, which may in turn lead to an
      absence of autophagy. The suggestion that LSDs can be defined as disorders of
      autophagy implies that there may be some overlap between pathological mechanisms
      of LSDs and more common neurodegenerative diseases, and this may help provide
      direction for future therapeutic strategies.

PMID- 20040310
TI  - Disease pathogenesis--clinical interpretation.

PMID- 20040312
TI  - The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick
      disease.
AB  - Patients with Niemann-Pick disease (NPD) Types A and B have an inherited
      deficiency of acid sphingomyelinase (ASM) activity. The clinical spectrum of this
      disorder ranges from the infantile neurological form that results in death by 3
      years of age (NPD Type A) to the non-neurological form that is compatible with
      survival into adulthood (NPD Type B). Intermediate cases have also been reported,
      and the disease is best thought of as a single entity with a spectrum of
      phenotypes. ASM deficiency is panethnic, but appears to be more frequent in
      individuals of Middle Eastern and North African descent. Current estimates of the
      disease incidence range from 0.5 to 1 per 100,000 births, although these
      approximations are thought to underestimate the true frequency of the disorder.
      The gene encoding ASM--SMPD1--has been studied extensively, and over 100
      mutations in SMPD1 have been found to cause ASM-deficient NPD. Based on these
      findings, DNA-based carrier screening has been implemented in the Ashkenazi
      Jewish community. ASM-knockout mouse models also have been generated and used to
      investigate disease pathogenesis and treatment with stem cell transplantation,
      gene therapy and enzyme replacement therapy (ERT). Based on these studies,
      clinical trials of ERT are underway in patients with non-neurological ASM
      deficient NPD.

PMID- 20040311
TI  - Autophagy in skeletal muscle: implications for Pompe disease.
AB  - Pompe disease is caused by an inherited deficiency of acid a-glucosidase (GAA), a
      lysosomal enzyme that catalyzes the breakdown of glycogen to glucose. In the
      absence of GAA, enlarged, glycogen-laden lysosomes accumulate in multiple
      tissues, although the major clinical manifestations are seen in cardiac and
      skeletal muscle. For many years, it was believed that the rupture of glycogen
      filled lysosomes was the major cause of the profound muscle damage observed in
      patients with Pompe disease. Here, we present evidence that a failure of
      productive autophagy in muscle tissue contributes strongly to disease pathology
      in both patients with Pompe disease and GAA-knockout mice. In the GAA-knockout
      mouse model, progressive accumulation of autophagic vesicles is restricted to
      Type II-rich muscle fibers. Not only does this build-up of autophagosomes disrupt
      the contractile apparatus in the muscle fibers, it also interferes with enzyme
      replacement therapy by acting as a sink for the recombinant enzyme and preventing
      its efficient delivery to the lysosomes. Our data indicate that a re-examination
      of the presumed pathological mechanism in Pompe disease is necessary, and suggest
      that successful treatment of patients with Pompe disease will require
      consideration of the dramatic failure of autophagy that occurs in this disease.

PMID- 20040313
TI  - Current state of the management of LSDs.

PMID- 20040314
TI  - Enzyme replacement therapy for the management of the mucopolysaccharidoses.
AB  - Enzyme replacement therapy (ERT) is now available for several of the
      mucopolysaccharidosis disorders. This brief review summarizes the role of ERT in
      reducing the burden of peripheral disease in many patients with
      mucopolysaccharidosis disorders, and describes the challenges that remain in
      treating the neurological manifestations of these conditions.

PMID- 20040315
TI  - Anderson-Fabry disease: developments in diagnosis and treatment.
AB  - Anderson-Fabry disease (commonly known as Fabry disease) is an X-linked disorder
      that is caused by deficiency of the lysosomal enzyme a-galactosidase A. The
      resulting accumulation of globotriaosylceramide leads to a wide spectrum of
      clinical signs and symptoms that affect many organs, including the kidneys, heart
      and brain. In recent years, our understanding of the natural history of Fabry
      disease has improved considerably, as have methods of clinical characterization
      and diagnosis. It is now apparent that this disorder may be much more common than
      previously suspected. The long-term efficacy of enzyme replacement therapy (ERT)
      in reducing disease burden in patients with Fabry disease continues to be
      demonstrated in clinical trials and observational studies; however, it is clear
      that ERT has limitations. This review provides an overview of current issues in
      the diagnosis and treatment of patients with Fabry disease and considers what may
      lie ahead in this rapidly evolving therapeutic area.

PMID- 20040316
TI  - Krabbe disease: an overview.
AB  - Krabbe disease (globoid cell leukodystrophy) is a neurodegenerative disorder that
      is caused by deficiency of the lysosomal enzyme galactosylceramidase. The
      resulting accumulation of incompletely metabolized galactocerebroside, which is a
      component of myelin, leads to progressive white matter disease. The severity of
      signs and symptoms is partly influenced by the causal mutations and corresponding
      residual enzyme activity. This review explains how the disease might manifest and
      discusses methods for diagnosis and staging of the disease process. The current
      understanding of the mechanisms underlying Krabbe disease is summarized, and
      therapeutic options--including current and investigational approaches--are
      outlined.

PMID- 20040317
TI  - LSDs and the immune system.

PMID- 20040318
TI  - Perspectives from B cell immunology: fact and fancy.
AB  - In this article, the formation of antibodies during enzyme replacement therapy
      (ERT) for lysosomal storage diseases (LSDs) is reviewed in the light of present
      day immunological concepts of immunogenicity and tolerance. Except in Gaucher
      disease, anti-enzyme antibodies frequently form (mainly immunoglobulin G) in
      patients receiving ERT, though they tend to wane as treatment continues. If the
      therapeutic enzyme is inhibited by antibodies, no significant modification to
      treatment is normally warranted, in clear contrast to therapy of hemophilia with
      clotting factors. The main adverse consequences of ERT, observed in only some
      patients, are sporadic hypersensitivity reactions, which are likely to be
      humorally mediated. Some infusion-related reactions are probably due to
      antibodies. In order to minimize immunogenicity, infused enzymes should be
      deaggregated and administered at low doses. In addition, inadvertent exposure to
      co-stimuli that might activate antigen-specific T or B lymphocytes should be
      avoided. The presence of cross-reacting immunological material, such as in
      patients with low levels or missense mutations of a gene coding for a lysosomal
      enzyme, tends to correlate with immune tolerance to the administered enzyme.
      There is a need for reliable biomarkers for therapeutic efficacy: some directions
      for further exploration are suggested. In animal models of LSDs, gene therapy
      delivered via viral vectors can rectify the lysosomal defect, and regulatory T
      cells that suppress antibody formation can be induced. This is a promising
      strategy that warrants further investigation in patients with LSDs.

PMID- 20040319
TI  - Management of infusion-related reactions to enzyme replacement therapy in a
      cohort of patients with mucopolysaccharidosis disorders.
AB  - OBJECTIVE: Enzyme replacement therapy (ERT) is currently available for the
      treatment of mucopolysaccharidosis (MPS) Type I, MPS II and MPS VI.
      Hypersensitivity reactions have been reported in some patients receiving ERT, but
      these can usually be easily managed. METHODS: In this retrospective study, we
      evaluated the manifestations and management of hypersensitivity reactions in
      patients at a single center who were receiving ERT for either MPS I, MPS II or
      MPS VI between 2002 and 2008. RESULTS: Hypersensitivity reactions were observed
      in 28 (36%) out of 77 patients, and were most common in children with severe
      disease. When an infusion-related reaction occurred, ERT was immediately
      suspended until the patient's symptoms had resolved. Antihistamines and
      antipyretics were administered to treat the acute symptoms of hypersensitivity
      reactions. In some patients, low-dose corticosteroids were administered to
      attenuate late-phase or biphasic reactions. There were no instances in which
      resuscitation was necessary. When ERT was restarted, patients were given
      premedication in the form of antihistamines and antipyretics, and ERT was
      administered at a slower rate. In most cases, this approach overcame the
      hypersensitivity. After gradually increasing the infusion rate, patients were
      generally able to resume a normal infusion schedule without premedication after a
      period ranging from 8 weeks to 3.5 years. CONCLUSION: Close monitoring of
      patients receiving ERT is essential. Use of an adapted ERT infusion regimen with
      premedication resulted in improvement of signs and symptoms of hypersensitivity
      in most of the patients who experienced infusion-related reactions.

PMID- 20040320
TI  - Novel therapies and future perspectives.

PMID- 20040321
TI  - Pharmacological chaperone therapy by active-site-specific chaperones in Fabry
      disease: in vitro and preclinical studies.
AB  - Many genetic disorders are due to protein misfolding and excessive premature
      degradation in the endoplasmic reticulum (ER). When a gene mutation does not
      affect the functionality of the protein, it may still promote the premature
      clearance of the protein by ER-associated degradation (ERAD), resulting in a loss
      of function. Competitive inhibitors are often effective active-site-specific
      chaperones when used at sub-inhibitory concentrations. Active-site-specific
      chaperones assist in the folding of mutant lysosomal enzymes in the ER, thereby
      promoting their escape from ERAD, enhancing trafficking to the lysosome and
      increasing the level of residual enzyme activity. In Fabry disease, degradation
      of various mutant forms of a-galactosidase A (alpha-gal A) has been shown to take
      place in the ER as a result of protein misfolding. One of the most potent
      inhibitors of alpha-gal A, 1-deoxygalactonojirimycin, has also been shown to be
      effective in enhancing residual alpha-gal A activity in cultured fibroblasts and
      lymphoblasts established from patients with Fabry disease caused by a variety of
      missense mutations. Oral administration of 1-deoxygalactonojirimycin to
      transgenic mice expressing a mutant form of human alpha-gal A (R301Q) yielded
      higher alpha-gal A activity in major tissues, compared with untreated transgenic
      mice.

PMID- 20040322
TI  - Delivery of recombinant proteins via the cerebrospinal fluid as a therapy option
      for neurodegenerative lysosomal storage diseases.
AB  - Patients with lysosomal storage diseases (LSDs) have a greatly diminished
      lifespan and reduced quality of life, particularly those with neurological
      manifestations. There are few therapeutic options available to treat the
      neurological signs and symptoms of LSDs. It is, therefore, imperative that
      efficacious and tolerable treatments are developed. Hematopoietic stem cell
      transplantation is carried out in some LSDs in which there is neurological
      involvement. However, this approach is associated with significant morbidity and
      mortality, and not all patients who receive this treatment exhibit improvements
      in cognitive signs and symptoms. A growing body of research in animal models of
      LSDs appears to support the efficacy of repeated delivery of recombinant
      lysosomal proteins via injection into the cerebrospinal fluid (CSF). Studies in
      dogs with mucopolysaccharidosis (MPS) Type 1 have shown that this approach
      enables widespread distribution of the recombinant protein within the brain,
      leading to a reduction in LSD pathology. Subsequent studies in MPS IIIA mice
      revealed that this strategy was also effective in ameliorating neuropathology and
      improving clinical signs in these animals. More recent studies in mice with
      Krabbe disease or a late infantile form of neuronal ceroid lipofuscinosis have
      demonstrated that delivery of recombinant proteins into the CSF may be
      efficacious in reducing disease pathology and neurological signs and symptoms.
      Whilst there are still important issues that need to be addressed, such as
      humoral immune responses to therapeutic protein administration and dose/
      frequency selection, this approach represents a medium-term option for treating
      these devastating conditions. This review summarizes some of the findings and
      challenges ahead.

PMID- 20040323
TI  - Novel treatments and future perspectives: outcomes of intrathecal drug delivery.
AB  - Intrathecal enzyme replacement therapy (ERT) holds promise as a treatment for the
      central nervous system manifestations of lysosomal storage diseases. Treatment
      via the cerebrospinal fluid represents a potential method of delivering
      recombinant enzyme across the blood-brain barrier. Experiments in animal models
      of mucopolysaccharidosis (MPS) Type I, MPS II and MPS IIIA have shown that ERT
      delivered via the intrathecal route distributes throughout the central nervous
      system and penetrates brain tissue, where it promotes clearance of lysosomal
      storage material. Studies are underway to investigate the safety and efficacy of
      intrathecal ERT in patients with MPS I.

PMID- 20040324
TI  - Gene therapy in metachromatic leukodystrophy.
AB  - Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by
      deficiency of the lysosomal enzyme arylsulfatase A. Deficiency of this enzyme
      results in intralysosomal storage of sphingolipid cerebroside 3-sulfates
      (sulfatides), which are abundant in myelin and neurons. A pathological hallmark
      of MLD is demyelination and neurodegeneration, causing various and ultimately
      lethal neurological symptoms. This review discusses the potential therapeutic
      application of hematopoietic stem cell gene therapy and intracerebral gene
      transfer (brain gene therapy) in patients with MLD.

PMID- 20040325
TI  - Clinical neuropathology.

PMID- 20040326
TI  - Malignant transformation in craniopharyngioma after radiation therapy: a case
      report and review of the literature.
AB  - OBJECTIVE: Craniopharyngioma is a benign epithelial tumor that is thought to
      arise from the remnant of the Rathke pouch. Malignant transformation in
      craniopharyngioma is extremely rare. Herein, we report a case of malignant
      transformation in craniopharyngioma after radiation therapy. MATERIALS AND
      METHODS: Histopathological and immunohistochemical analyses were carried out for
      specimens of the suprasellar tumor (from three resections, with the third surgery
      performed after radiation therapy). RESULTS: The resected tumors from the first
      and second surgeries comprised islands of loosely cohesive aggregates of
      epithelial cells, so-called stellate reticulum. At the periphery of the nests,
      palisaded columnar epithelium was observed. Wet keratins were scattered, and few
      mitotic figures were seen. The third surgical specimen was composed of irregular
      large nests of basaloid cells that had large, round to oval nuclei with prominent
      nucleoli, and mitotic figures were frequently seen (21/10 high power fields). In
      the center of the nests, eosinophilic ghost cells, resembling wet keratin, were
      observed. Accordingly, the diagnosis of malignant transformation in
      craniopharyngioma was made. Immunohistochemical studies revealed that the p53
      protein was over-expressed in the malignant component, whereas its expression was
      much lower in the benign component. CONCLUSIONS: Similar to the ten previously
      reported cases of malignant transformation in craniopharyngioma, the present case
      occurred after radiation therapy. p53 protein overexpression was also observed in
      the earlier cases of malignant craniopharyngioma as well as in the present case
      (6/6 cases). We concluded that radiation therapy and p53 mutations could be
      involved in malignant transformation in craniopharyngioma.

PMID- 20040327
TI  - Intracranial extension of salivary gland tumors.
AB  - OBJECTIVE: The aim of this report is to describe 3 cases of salivary gland tumors
      with intracranial extension associated to an extracerebral mass lesion, and to
      discuss the frequence, pathology and treatment of these very rare localizations.
      CLINICAL MATERIAL: The 3 patients were 1 woman and 2 men, aged 44, 53 and 74
      years, respectively. The primary tumors were an adenocarcinoma and a malignant
      oncocytoma of the parotid gland and an adenoid cystic carcinoma of the
      submandibular gland. The location of the intradural extra-axial tumor was the
      middle fossa and temporal region in 2 cases and the cerebellopontine angle in 1.
      Surgical treatment consisted in the seemingly complete removal of 2 tumors with
      middle fossa localization and partial removal of the cerebellopontine angle
      lesion. Radiotherapy was administered in all 3 cases and chemotherapy in 2.
      RESULTS: 1 patient is alive and free of recurrence 32 months after removal of the
      intracranial tumor; 2 other patients died 28 months and 12 months
      postoperatively. CONCLUSIONS: The intracranial extension of salivary gland tumors
      is a very rare event. An aggressive surgical resection followed by radiotherapy
      is justified in cases with significant intracranial mass lesions and scarce bone
      and dural involvement.

PMID- 20040328
TI  - Oncocytic choroid plexus carcinoma: case report.
AB  - Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic
      transformation. A 13-month-old girl presented with acute lethargy which quickly
      progressed to coma. A CT scan of the head revealed impending herniation due to
      hemorrhage within an intracranial tumor. An MRI scan showed a large, partly
      cystic and highly vascular left lateral ventricular mass. A near total resection
      was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma
      with extensive oncocyti c transformation. A minor portion of the moderately to
      poorly differentiated tumor exhibited classical microscopic features of choroid
      plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10
      HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the
      large, eosinophilic, cytologically malignant but granular-appearing oncocytes
      comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity
      and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year
      consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with
      oncocytic transformation has not been previously reported. The remarkable extent
      of this alteration and its clinical significance remains to be determined.

PMID- 20040329
TI  - Primary angioleiomyoma in the sellar region: a case report and literature review.
AB  - OBJECTIVE: Angioleiomyoma (vascular leiomyomas, angiomyoma) is a rare, benign
      soft tissue tumor which consists of a mixture of well-differentiated smooth
      muscle cells and thick-walled vessels. Here we report a case of angioleiomyoma in
      the sellar region, which is the first case report of angioleiomyoma at this
      anatomical location. CLINICAL PRESENTATION: A 53-year-old man was admitted with a
      medical history of three months episodic headache and one month visual
      deterioration, both of which progressed gradually. The neurological examination
      showed nothing remarkable except a slightly decreased adrenocorticotrophic
      hormone (ACTH) level. Preoperative magnetic resonance imaging revealed a
      pituitary apoplexy. Gross total resection of the tumor was then performed.
      PATHOLOGICAL FINDINGS: Histological and immunohistochemical studies showed a
      typical microscopic appearance of an angioleiomyoma present in a rather uncommon
      place. The pertinent literature regarding the features of this tumor was reviewed
      and discussed. CONCLUSIONS: Intracranial angioleiomyoma is a benign soft tissue
      tumor with excellent prognosis. Early diagnosis of this tumor is difficult.

PMID- 20040330
TI  - Lymphocytic hypophysitis with normal pituitary function mimicking a pituitary
      adenoma: a case report and review of literature.
AB  - Lymphocytic hypophysitis (LYH) is a rare autoimmune inflammatory disorder of the
      pituitary gland usually affecting young women, often in pregnancy or post partum
      period. It is rare in non-pregnant females and in men. Patients present with
      symptoms of an expanding pituitary mass and/or varying degrees of pituitary
      dysfunction. We, hereby report a case of lymphocytic hypophysitis in a 28-year
      old non-pregnant female who presented with clinical and radiological features of
      a pituitary tumor with normal pituitary hormones which on histopathological
      examination revealed features of lymphocytic hypophysitis. The case is presented
      here for its rarity and its unique presentation as an expanding pituitary mass
      with normal pituitary function. Peculiar clinical, radiological and
      histopathological features of this uncommon entity are discussed.

PMID- 20040331
TI  - Role of dentate gyrus alterations in mesial temporal sclerosis.
AB  - Drug-resistant chronic temporal lobe epilepsy is the most common type of epilepsy
      that undergoes surgical treatment. To verify if dentate gyrus alterations may
      play a role in patients with mesial temporal sclerosis (MTS), 14 patients,
      submitted to epilepsy surgery, were selected. Only cases with MTS alone were
      included. Granule cell dispersion (GCD) was observed in 7 cases (50%). A
      statistically significant correlation between GCD and the mean number of
      seizures/month was evidenced. The percentage of patients who did not achieve
      seizure relief (i.e. they were not in Engel class 1A) was 57.14% in patients
      without GCD, whereas that percentage dropped to 14.29% in patients with GCD. The
      association between a more favorable postsurgical epileptogenic outcome and
      granule cell pathology in patients with MTS has been observed, thus suggesting
      that dentate gyrus alterations may play a role in drug-resistant TLE.

PMID- 20040332
TI  - Late onset glycogen storage disease type II with reducing body-like inclusions.
AB  - Skeletal muscle tissue from 3 patients with clinical diagnosis of limb girdle
      muscular dystrophy revealed a vacuolar myopathy with glycogen storage and
      lysosomal activity. A diagnosis of late onset GSD Type II was considered. An
      interesting finding was the presence of round to oval eosinophilic inclusions
      which reduced on menadione linked a-glycerophosphate dehydrogenase (MAG). There
      are only two reports in the literature describing similar inclusions in late
      onset GSD II. We report morphological findings of this rare disorder and compare
      the findings with earlier two reports.

PMID- 20040333
TI  - Neuropathological biomarker candidates in brain tumors: key issues for
      translational efficiency.
AB  - Brain tumors comprise a large spectrum of rare malignancies in children and
      adults that are often associated with severe neurological symptoms and fatal
      outcome. Neuropathological tumor typing provides both prognostic and predictive
      tissue information which is the basis for optimal postoperative patient
      management and therapy. Molecular biomarkers may extend and refine prognostic and
      predictive information in a brain tumor case, providing more individualized and
      optimized treatment options. In the recent past a few neuropathological brain
      tumor biomarkers have translated smoothly into clinical use whereas many
      candidates show protracted translation. We investigated the causes of protracted
      translation of candidate brain tumor biomarkers. Considering the research
      environment from personal, social and systemic perspectives we identified eight
      determinants of translational success: methodology, funding, statistics,
      organization, phases of research, cooperation, self-reflection, and scientific
      progeny. Smoothly translating biomarkers are associated with low degrees of
      translational complexity whereas biomarkers with protracted translation are
      associated with high degrees. Key issues for translational efficiency of
      neuropathological brain tumor biomarker research seem to be related to (i) the
      strict orientation to the mission of medical research, that is the improval of
      medical practice as primordial purpose of research, (ii) definition of research
      priorities according to clinical needs, and (iii) absorption of translational
      complexities by means of operatively beneficial standards. To this end, concrete
      actions should comprise adequate scientific education of young investigators, and
      shaping of integrative diagnostics and therapy research both on the local level
      and the level of influential international brain tumor research platforms.

PMID- 20040334
TI  - Phenotyping with sulfasalazine - time dependence and relation to NAT2
      pharmacogenetics.
AB  - OBJECTIVE: N-acetyltransferase 2 (NAT2) genotype-phenotype relation with
      sulfasalazine as probe drug by means of detailed genotype analysis and kinetic
      data evaluation. BACKGROUND: Though phenotype analysis of sulfasalazine
      metabolism has been described before, genotype investigations in this regard are
      scarce. The influence of different single point mutations on the metabolism of
      the sulfasalazine metabolite sulfapyridine (SP) should give more insight into the
      functionality of different alleles especially with those still under discussion.
      METHODS: In two bioavailability studies performed under comparable conditions
      with 24 healthy subjects of both genders equally distributed, plasma levels of SP
      and acetylsulfapyridine (Ac-SP) were determined after oral intake of enteric
      coated formulations of sulfasalazine (500 mg and 1,000 mg, respectively). The
      resulting metabolic ratios were calculated. NAT2 genotype was analyzed in
      parallel for all subjects deducing haplotype set as well as putative functional
      phenotype as (homozygous or heterozygous) rapid acetylator (RA) or slow
      acetylator (SA) and correlated with the PK results. RESULTS AND DISCUSSION: RA
      genotype in the overall study population was seen with 45.5% (including 6.8%
      homozygous wildtype *4/*4) and SA genotype with 54.5%. Compared to RA genotype,
      apparent terminal elimination half-life of SP as well as of Ac-SP was prolonged
      in the SA genotype population, C(max) and AUC values of SP were higher whereas
      average C(max) value of Ac-SP was lower (with AUC only some tendency to lower
      values). In general, phenotype-genotype correlation was good with only few
      exceptions. Strongest functional effect on enzyme activity was noticed in slow
      acetylators carrying the 341T > C mutation, followed by 590G > A mutation whereas
      the influence of 857G > A was considerably less pronounced. Homozygous 803A > G
      mutation (lysine > arginine shift) did not reveal enzyme activity reduction.

PMID- 20040335
TI  - Population pharmacokinetic study of methotrexate in children with acute
      lymphoblastic leukemia.
AB  - A population pharmacokinetic model was developed to describe the factors that may
      affect the pharmacokinetics of methotrexate (MTX) in Chinese child patients with
      acute lymphoid leukemia (ALL) and to predict the individual pharmacokinetic
      parameters in these patients. One hundred and eighteen children with ALL who
      received MTX at the dose of 2 - 3.5 g/m(2) were enrolled in this study. 96
      children were enrolled in the index group and 22 children in the validation
      group. The data were analyzed using nonlinear mixed effect model (NONMEM)
      software. A linear two-compartment model with linear elimination best described
      the data. The forward inclusion-backward elimination method was used to
      investigate the different covariates, including age, body weight, gender, etc.
      The Bayesian method was used to predict the individual pharmacokinetic
      parameters. Validation was applied using an internal and external approach. The
      population pharmacokinetic parameters and 95% confidence interval (CI) were
      obtained as follows: The clearance of central compartment (CL1), apparent volume
      of distribution of central compartment (V1), the clearance between central and
      peripheral compartment (CL2), and apparent volume of distribution of peripheral
      compartment (V2) were 5.04 (3.93 - 6.15) l/min, 16.1 (12.5 - 19.7) l, 0.203
      (0.102 - 0.304) l/min and 7.05 (3.86 - 10.20) l, respectively. The inter
      individual variability of CL1, V1, CL2, and V2 were 49.60%, 29.36%, 137.64%, and
      107.70%, respectively. Gender, body surface area and the amount of alkalinization
      agent during 24 hours before MTX administration had significant effects on CL1. A
      strong relationship was found in this study between CL2 and age, as well as
      between V2 and age. A good correlation was further proved through the validation
      model. Moreover, some secondary pharmacokinetic parameters were estimated: the
      elimination half-life t1/2 was 2.34 h (CV = 36.7%), elimination constant k(e) was
      0.33 h(-1) (CV = 33.2%), and the area under plasma concentration versus time
      curve AUC was 582.92 mg x h x l(-1) (CV = 55.9%). Our model combine Bayesian
      approach enabled a satisfactory estimation of MTX concentration in individual
      patients. The results of this study allowed clinicians to assess the MTX
      pharmacokinetic parameters based on the specific demographic characteristics of
      patients.

PMID- 20040336
TI  - Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid
      secretion via the PPARalpha-MDR3 pathway.
AB  - OBJECTIVE: Bezafibrate (BF) has been used to treat biliary damage, particularly
      in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has
      been demonstrated. The mechanism of action is thought to involve activation of
      the PPARalpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this
      hypothesis in patients with hepatobiliary disease. METHODS: The levels of serum
      gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile
      components were examined before and after BF administration in patients with
      obstructive jaundice undergoing percutaneous transhepatic biliary drainage
      (PTBD). Hepatic expression of PPARalpha and MDR3 was quantified by real-time PCR
      in patients with PBC or non-alcoholic fatty liver disease (NAFLD). RESULTS: In
      patients with obstructive jaundice, BF decreased the serum levels of biliary
      enzymes and increased the bile concentration of PL. In patients with PBC or
      NAFLD, the expression levels of MDR3 were already up-regulated before starting
      the BF treatment. Although BF treatment did not further up-regulate MDR3
      expression in NAFLD patients, PPARalpha expression was significantly increased.
      CONCLUSIONS: BF enhanced the secretion of PL into bile in cholestatic patients
      undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent
      cholesterol overload, MDR3 was already expressed at a high level to compensate
      for bile acids overproduction, and its expression was hardly affected by BF. In
      patients with chronic liver diseases such as PBC, BF may induce clinical effects
      via mechanisms independent of PL secretion.

PMID- 20040337
TI  - Appropriate dosing in patients with impaired renal function on medical wards
      before and after an educational intervention.
AB  - CONTEXT: Whereas in larger hospitals individualized dose adjustment in renal
      insufficiency can be provided by expert systems and pharmacists, these options
      are often not available in smaller hospitals. AIMS: We evaluated whether one
      short educational session for the medical staff of internal wards of a community
      hospital, focusing on creatinine clearance and dosing in renal insufficiency, and
      providing a list of frequently used drugs and their dosing schedule does reduce
      the rate of patients with unadjusted doses. MATERIAL AND METHODS: In patients
      with a creatinine clearance < 60 ml/min, dosing schedules for 92 drugs were
      determined. After a 6-month observation period (Cohort 1), an educational
      intervention and the above mentioned list were delivered to the medical staff.
      This intervention was followed by a further 6-months observation period (Cohort
      2). RESULTS: In Cohort 1, 55/85 patients (median age 79 y) had at least one
      initially inappropriately adjusted medication, and 47/85 remained so at
      discharge, whereas in Cohort 2 (median age 77 y), 28/85 patients had at least one
      initially inappropriately adjusted medication (p = 0.014 compared to Cohort 1)
      and 27/85 remained so at discharge (p = 0.05). In Cohort 1, 46.0% of all
      prescriptions with drugs which need dose adjustment (n = 220) were not adjusted.
      After the intervention (Cohort 2), 25.6% of all prescriptions (n = 176) followed
      an unadjusted dosage (p < 0.001). CONCLUSION: This intervention was on a "low
      key"-level, and no further support e.g. academic detailing was effected. Despite
      this, we found a considerable reduction in the number of inappropriate doses in
      patients with impaired renal function.

PMID- 20040338
TI  - Effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of atorvastatin
      and 2-hydroxyatorvastatin in healthy Korean subjects.
AB  - OBJECTIVE: This study aimed to evaluate the effect of genetic polymorphisms of
      SLCO1B1 and ABCB1 on the pharmacokinetics of atorvastatin and its metabolites.
      METHODS: 290 Koreans were genotyped for SLCO1B1, ABCB1 and CYP3A5, and 28
      subjects were selected for the pharmacokinetic study. Each subject received a
      single oral dose of 20 mg atorvastatin and blood samples were collected up to 48
      hr after dosing. The relationship between the genotypes and atorvastatin
      pharmacokinetics was examined. RESULTS: For SLCO1B1 genotypes, the mean area
      under the concentration-time curve from time 0 to infinity (AUC0-infinity) of
      atorvastatin was 148.2 ng x hr/ml for *15/*15 subjects (n = 3), which was
      significantly larger than for 1a/*15 and *1b/*15 (n = 8) (80.7 ng x hr/ml, p =
      0.0121) and also larger than for *1a/*1a, *1a/*1b and *1b/*1b (n = 17) (66.3 ng x
      hr/ml, p = 0.0018). The mean AUC0-infinity of 2-hydroxyatorvastatin for *15/*15
      was also larger than in *1a/*1a, *1a/*1b and *1b/*1b (p = 0.012). In lactone
      forms, no significant pharmacokinetic difference was found among the genotypes.
      For ABCB1 genotypes, the half-lives of atorvastatin, atorvastatin lactone, 2
      hydroxyatorvastatin and 2-hydroxyatorvastatin lactone were significantly longer
      in c.2677TT-c.3435TT (n = 3) vs. c.2677GG-c.3435CC and c.2677GT-c.3435CT (n =
      10), yielding p = 0.049, 0.007, 0.007 and 0.007, respectively. CONCLUSION: This
      study shows that the SLCO1B1*15 allele may be associated with the individual
      difference in the AUC0-infinity of atorvastatin whereas the ABCB1 TT-TT diplotype
      may affect the elimination half-life of the drug in the Korean population.

PMID- 20040339
TI  - Pharmacokinetics of alogliptin when administered with food, metformin, or
      cimetidine: a two-phase, crossover study in healthy subjects.
AB  - OBJECTIVE: The dipeptidyl peptidase-4 inhibitor alogliptin, under development for
      treatment of Type 2 diabetes, primarily is excreted renally. This study
      investigated (1) the effect of food on alogliptin pharmacokinetics and
      tolerability and (2) pharmacokinetic interactions between alogliptin and
      metformin or cimetidine and tolerability of alogliptin when administered with
      either drug. METHODS: This randomized, open-label, two-phase, crossover study
      recruited healthy adults. In the single-dose phase, 36 subjects received an oral
      dose of alogliptin 100 mg under fed or fasted conditions. In the multiple-dose
      phase, subjects in one arm (n = 17) received 6 days each of alogliptin 100 mg
      once daily (q.d.), metformin 1,000 mg twice daily (b.i.d), and alogliptin q.d. +
      metformin b.i.d; subjects in the other arm (n = 18) received 6 days each of
      alogliptin 100 mg q.d., cimetidine 400 mg q.d., and alogliptin q.d. + cimetidine
      b.i.d. Pharmacokinetic parameters were determined after the last dose in each
      period. Tolerability was assessed through adverse events and clinical findings.
      RESULTS: Food had no effect on alogliptin area under the concentration-time curve
      (AUC) from 0 h to infinity and a small, clinically insignificant effect on
      maximum plasma concentration (C(max)) (fed/fasted least squares (LS) geometric
      mean ratio, 0.856; 90% confidence interval (CI), 0.798 - 0.917). Metformin and
      cimetidine did not affect alogliptin pharmacokinetics. Alogliptin had no effect
      on metformin C(max) and a small, clinically insignificant effect on AUC over the
      dosing interval ((alogliptin + metformin)/metformin LS geometric mean ratio,
      1.19; 90% CI, 1.095 - 1.291). Alogliptin did not affect cimetidine
      pharmacokinetics. Alogliptin tolerability was similar under all conditions.
      CONCLUSION: Alogliptin can be administered without regard to meals and with
      metformin or cimetidine without the need for dose adjustment.

PMID- 20040340
TI  - Storage, utilization and cost of drug products in Palestinian households.
AB  - BACKGROUND AND OBJECTIVE: Appropriate storage and use of medications in
      households may decrease drug wastage and unnecessary hazard. The objective of
      this study was to investigate storage, utilization habits and cost of medications
      in households in Palestine. METHODS: This is a cross sectional, anonymous,
      questionnaire-based study of 465 households in northern Palestine. The drug
      product inventory in the surveyed households was investigated and family members
      were interviewed. RESULTS: A total of 465 households were assessed, 50 were
      excluded. The total number of drug products in the 415 households was 5,505; the
      mean + or - SD was 13.3 + or - 7.8. Level of father's education, presence of
      chronic disease and insurance coverage were the variables that showed a
      significant relationship with the amount of drug products found in the
      households. Most of the drug products (43.4%) were stored in relatively unsafe
      places in the house within the reach of children. Approximately one third (32.5%)
      of the drug products were not in their original container. The percentages of
      unused drug products, expired, or those with no clear expiry date were 32.7%,
      17.7% and 11% respectively. Estimated drug wastage in the 415 households and
      nationwide would be 16,100 and 19 million USD respectively. The most common drug
      categories encountered in households were alimentary, musculoskeletal and anti
      infective agents. The most common individual drugs encountered were: paracetamol
      (8.5%), ibuprofen (4.9%) and diclofenac (3.7%). CONCLUSION: Medications were
      stored in large quantities in Palestinian households, and a large percentage was
      being wasted. Drug-use assessments and a comprehensive evaluation of the current
      national drug policies are warranted to curtail this problem.

PMID- 20040341
TI  - Antihypertensive drug utilization and conformity to guidelines in a sub-Saharan
      African hypertensive population.
AB  - BACKGROUND: Despite availability and usage of wide array of antihypertensive
      drugs, blood pressure has remained poorly controlled in most health care settings
      particularly in Africa. The cost of these drugs among other factors strongly
      determines the prescription and usage pattern which ultimately affects control of
      blood pressure particularly in sub-Saharan Africa. The aim of this study was to
      describe the current utilization pattern of antihypertensive drugs in a tertiary
      hospital in Nigeria in line with the regional and international guidelines for
      hypertension management and to compare with similar studies in other parts of the
      country to generate the national outlook. METHODS: This is a cross sectional
      study of 805 adult hypertensive patients who were on treatment at the Medical Out
      Patient Department of University of Ilorin Teaching Hospital in Nigeria, a
      country with the most populous black hypertensive patients. Data were collated
      from the patients' records and evaluated according to drug classifications.
      RESULTS: 787 patients out of the 805 evaluated were eventually included in the
      analysis. Mean age was 57.88 + or - 12.59 years with 490 (62.3%) females.
      Frequency of use of classes of antihypertensive was: diuretics (D, 84%), calcium
      channel blockers (CCB, 66%), angiotensin converting enzyme inhibitors (ACEI,
      65%), a-methyldopa (ALD, 26%), beta-blockers (BB, 11.9%) and angiotensin receptor
      blockers (3.8%). Proportions of number of drugs usage per patient were: 0 (2.2%),
      1 (9.1%), 2 (37.1%), 3 (35.8%), 4 (15.6%), and 5 (0.1%). The most commonly used
      combinations of drugs were ACEI + CCB + D (21.6%), followed by CCB + D (14.5%),
      ACE + D (11.4%) and ACEI + D + ALD (9.8%). Other recent studies in Nigeria
      revealed diuretics and multiple agents as the prevalent prescription pattern.
      CONCLUSION: Antihypertensive utilization in Ilorin, Nigeria like some parts of
      the country conforms to the guidelines for the management of hypertension in
      blacks with majority of patients on diuretics particularly in combination with
      other agents. Angiotensin converting enzyme inhibitors are increasingly being
      used whereas beta-blockers and angiotensin receptor antagonists are still less
      utilized.

PMID- 20040342
TI  - Sildenafil induced choreoathetosis in men with Parkinson's disease.
AB  - OBJECTIVE: The present report describes a case of choreoathetotic movements which
      were most probably induced by sildenafil in a patient with Parkinson's disease
      (PD) treated with levodopa/carbidopa (LD/CD). CASE SUMMARY: A 56-year-old retired
      man was admitted to hospital because of bizarre, involuntary movements and
      anxiety. Before admission he had taken sildenafil 100 mg. He had a previous
      history of PD for 5 years and during the last 3 years he was stable with long
      acting LD/CD and selegiline. He is in Stage 2 according to Hoehn and Yahr Staging
      of PD. The patient did not have any problems with erectile function and he took
      sildenafil 50 minutes after the last daily dose of LD/CD. The patient was
      discharged from the hospital 12 hours after the admittance without any symptoms
      of choreoathetosis. CONCLUSION: Choreoathetotic dyskinesia is an adverse effect
      which was provoked by sildenafil administration (drug abuse) in a previously
      stabile responder to LD therapy, but probably had a lower threshold for
      dyskinesia. Predisposition for this pharmacokinetic interaction could be a short
      time interval between LD and sildenafil applied in high dosage.

PMID- 20040343
TI  - Protracted deep coma after bromazepam poisoning.
AB  - BACKGROUND: Bromazepam intoxication is very common but surprisingly rarely
      reported. CASE DESCRIPTION: We describe the case of a 73-year-old woman who
      suffered from a prolonged coma after acute self poisoning with bromazepam (serum
      concentration of 2,000 ng/ml at admission, 2 - 10 hours after ingestion of up to
      180 mg) and zolpidem (900 ng/ml at admission). Only the former lasted at toxic
      concentrations. Recovery of consciousness allowed extubation on Day 16. Repeat
      dose activated charcoal (25 g every 6 h from Day 14 to 16) resulted in minimal
      effects on bromazepam grossly estimated kinetics. CONCLUSION: Despite its
      relatively low theoretic half-life, bromazepam may induce a prolonged life
      threatening coma, even in the absence of renal or hepatic failure.

PMID- 20040344
TI  - Metabolic syndrome in mental illness: evidence and way out.

PMID- 20040345
TI  - Effect of statins on erythropoietin responsiveness in type 2-diabetic versus non
      diabetic hemodialysis patients.
AB  - AIMS: This study investigated whether the antiinflammatory effect of statins
      improved erythropoietin responsiveness in hemodialysis patients. We also examined
      if Type 2 diabetes mellitus, which had been shown to increase erythropoietin
      resistance, affected this effect of statins. METHODS: 103 patients were included
      in the cross-sectional study. Patients were stratified into statin and non-statin
      groups, and subgrouped based on the presence of Type 2 diabetes mellitus.
      Demographic, laboratory and other relevant data were analyzed by independent
      sample t-tests. The outcome of interest was erythropoietin dose. Two-way analysis
      of variance was used to determine the interaction between the use of statins and
      the presence of Type 2 diabetes mellitus. RESULTS: Of 103 patients, 34% were on
      statins and 38.8% were diabetic. The mean erythropoietin dose (units/kg per week)
      was significantly lower in the statin group (275.6 +/- 273.2, 449.5 +/- 555.9, p
      < 0.05). 20% of patients in the statin group required erythropoietin dose in
      excess of an epoetin equivalent of 500 units/kg per week, compared to 30.88% in
      the non-statin group. The mean C-reactive protein level (mg/l) was lower in the
      statin group, although there was no statistical significance (1.13 +/- 1.22, 1.77
      +/- 2.43, p = 0.08). The two-way analysis of variance showed no interaction
      between the use of statins and the presence of Type 2 diabetes mellitus on
      erythropoietin dose. CONCLUSIONS: Our study demonstrated that hemodialysis
      patients who were on statins had a significantly lower erythropoietin
      requirement. This association is possibly due to the pleiotropic effect of
      statins.

PMID- 20040346
TI  - Serum-soluble Fas and serum levels of erythropoietin in chronic kidney disease.
AB  - BACKGROUND: Soluble Fas levels (sFas) are increased in the serum of uremic
      patients and are associated with the presence of anemia and recombinant human EPO
      (rHuEPO) dosage in dialysis patients. It is possible that sFas levels are
      associated with an increased need for serum erythropoietin levels (Epo) in
      chronic kidney disease and dialysis patients in order to maintain hematocrit
      (Hct) levels. AIMS: To investigate the relationship between serum sFas levels,
      serum Epo levels and the ratio between Epo levels and Hct in uremic patients.
      METHODS: We studied 52 predialysis chronic kidney disease patients (CKD; 33 M, 57
      +/- 12 years, hematocrit (Hct) = 37 +/- 7%), 29 peritoneal dialysis patients (PD;
      12 M, 54 +/- 14 years, Hct = 36 +/- 7%), 29 hemodialysis patients (HD; 19 M, 47
      +/- 14 years, Hct = 33 +/- 5%) and 29 healthy volunteers (control group 17 M, 50
      +/- 16 years, Hct = 43 +/- 3%). We examined the relationship between Hct and
      serum levels of Epo, sFas, C-reactive protein, IL-6 and iron status. The ratio of
      serum Epo divided by Hct (Epo/Hct) was used as an indicator of Epo
      responsiveness. RESULTS: Compared to normal subjects, the CKD, PD and HD groups
      presented lower Hct levels and higher serum levels of sFas, Epo, Epo/Hct and IL
      6. Serum levels of sFas correlated negatively with albumin (r = -0.24, p = 0.02),
      IL-6 (r = -0.18, p = 0.04) and Epo/Hct (r = -0.37, p < 0.001). In multivariate
      analysis, after adjusting for markers of iron store and inflammation, only sFas
      correlated with Epo/Hct. In the CKD group, there were negative correlations
      between serum levels of sFas and glomerular filtration rate (GFR) (r = -0.45, p <
      0.001) and between Epo/Hct and GFR (r = -0.32; p = 0.02). There was a positive
      correlation between Epo/Hct and serum levels of sFas in the CKD group (r = 0.31,
      p = 0.03) and in the HD groups (r = 0.58, p = 0.001). CONCLUSION: Our findings
      show that serum sFas is associated with higher Epo/Hct ratio, suggesting that
      sFas may be a marker of Epo hyporesponsiveness in uremia. Further studies are
      needed to determine whether sFas is just a marker of Epo hyporesponsiveness or is
      also involved in its pathophysiology.

PMID- 20040347
TI  - The relationship between serum level of N-terminal pro-B-type natriuretic peptide
      and nutritional status, and inflammation in chronic hemodialysis patients.
AB  - BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-pro BNP), a biomarker
      of heart failure, is involved in regulation of the body fluid homeostasis and
      vascular tone. The purpose of this study was to investigate the relationship
      between serum level of NT-pro BNP and nutritional status, inflammation and
      hydration in patients on maintenance hemodialysis (HD). MATERIALS AND METHODS:
      The study involved 97 HD patients (mean age: 65.3 +/- 13.9 years, HD duration:
      36.3 +/- 43.5 months). Blood tests comprised the measurements of serum levels of
      NT-pro BNP, interleukin-6 (IL-6), human soluble tumor necrosis factor receptor I
      (s TNF RI), hemoglobin (Hb), albumin (alb) and urea. Furthermore, normalized
      protein catabolic rate (n PCR), body mass index (BMI), mean arterial blood
      pressure (MAP), adequacy of HD (Kt/V), and interdialytic body weight gain (IBWG)
      were calculated. In addition, NT-pro BNP was measured in a healthy control group
      (CG; n = 24, mean age 49.5 +/- 15.0 years). Hydration status was determined by
      bioimpedance analysis (BIA). RESULTS: Irrespective of gender, NT-pro BNP levels
      were markedly elevated in HD patients compared with CG (15879.2 +/- 14033.3 pg/ml
      vs. 73.45 +/- 23.56 pg/ml; p < 0.00001). NT-pro BNP was unrelated to any measures
      of body fluid compartments. Multivariate regression analysis revealed that only
      four parameters (nPCR, Hb, MAP, and total time on HD) influenced serum NT-pro BNP
      levels. CONCLUSION: While there was only moderate direct association of NT-pro
      BNP with hydration status, it was elevated in patients with intensive catabolism,
      severe anemia, higher MAP and longer total duration of HD.

PMID- 20040348
TI  - B-type natriuretic peptide and severe heart failure at baseline predict overall
      mortality in incident dialysis patients.
AB  - AIMS: The B-type natriuretic peptide (BNP) has become increasingly important as a
      diagnostic and prognostic method for cardiovascular disease or death. To our
      knowledge no prospective studies exist to evaluate the value of baseline BNP and
      baseline heart failure as predictors of overall death in incident rather than
      prevalent hemodialysis patients with end-stage renal disease (ESRD). METHODS: 255
      ESRD patients were included in our observational study with a median observation
      period of 1.11 years. A Kaplan-Meier survival curve was stratified by BNP
      concentration (< 340 pg/ml and > or = 340 pg/ml) to estimate the impact on the
      overall mortality rate. Univariate and multiple Cox regression models were fitted
      for a variety of covariables including severe heart failure (graded according to
      the New York Heart Association) to evaluate the independent predictors of death.
      Association between BNP and four explanatory variables was described in a
      multiple linear regression model. RESULTS: Survival analysis demonstrated a
      significantly higher mortality rate in patients with higher BNP values at
      baseline. The independent predictive value of high BNP concentration at baseline
      could be statistically confirmed by multiple Cox regression analysis. However,
      when including the covariates hemoglobin and severe heart failure, significantly
      associated with BNP, in the same model, severe heart failure rather than BNP
      becomes a significant predictor of overall death. CONCLUSIONS: A higher BNP level
      at baseline may be confirmed as an independent predictor of death in the incident
      dialysis population. However, severe heart failure may affect the impact of BNP
      on the overall survival rate and thus be a stronger predictor of death than BNP.

PMID- 20040349
TI  - Metal ion and vitamin adsorption profiles of phosphate binder ion-exchange
      resins.
AB  - AIMS: To determine the metal ion and vitamin in vitro adsorption profile of
      sevelamer hydrochloride (sevelamer-HCl) and colestilan(INN)/colestimide(JAN), a
      novel ion-exchange resin being developed as a phosphate binder for end-stage
      renal disease (ESRD) patients undergoing hemodialysis, adsorption of metal ions
      (iron, cobalt, copper and zinc) and vitamins (B6, B12, C, K and folic acid)
      essential for hematopoiesis/blood coagulation was assessed. METHODS: Mixtures of
      each resin (colestilan or sevelamer-HCl, 4 mg/ml) and metal ions (Fe(III),
      Fe(II), Co(II), Cu(II), and Zn(II), 1 microg/ml) were adjusted to pH 1.2 or 6.8
      and incubated at 37 degrees C for 1 hour. Metal ions in the recovered filtrate
      were detected by inductively coupled plasma optical emission spectrometry. In
      addition, the mixtures of each resin (4 mg/ml) and vitamins (B6, B12, C, K and
      folic acid, 0.5 - 250 microg/ml) were adjusted to pH 6.8 and incubated at 37
      degrees C for 0.5 hour. The vitamin concentrations in the recovered filtrate were
      quantified by HPLC. RESULTS: Colestilan did not adsorb any metals tested at
      either pH level, whereas sevelamer-HCl adsorbed copper(II) and zinc(II) ion at pH
      6.8 with adsorption ratios of 99% and 38%, respectively. Both resins showed
      almost complete adsorption of vitamin C, vitamin K, and folic acid, but weak
      adsorption of vitamin B6, and no adsorption of vitamin B12. CONCLUSIONS: The
      differing adsorption profiles for metal ions and vitamins between sevelamer-HCl
      and colestilan may be of importance for the individualized management of anemia
      and malnutrition in chronic hemodialysis patients receiving phosphate binding ion
      exchange resins for the control of hyperphosphatemia.

PMID- 20040350
TI  - Emotional symptoms, quality of life and cytokine profile in hemodialysis
      patients.
AB  - BACKGROUND: Mental disorders are frequent in hemodialysis (HD) patients.
      Depression and anxiety along with physical co-morbidity affect quality of life
      (QOL). Uremia is associated with inflammation and release of cytokines by
      lymphomonocytes. Inflammatory cytokines are relevant in depression. The aim of
      this study was to assess the psychological alterations and QOL in HD patients,
      and to correlate them with pattern of cytokine production. METHODS:  PATIENTS: 30
      HD patients and 20 subjects with CKD Stage I-II K-DOQI. Psychometric tests were
      administered: 1) Hospital Anxiety and Depression Scale (HADS) composed of an
      anxiety subscale (HADS-A) and a depression subscale (HADS-D); 2) Kidney Disease
      Quality of Life (KDQOL) modified, including a cognitive function subscale (KDQOL
      CF). Whole blood samples collected at beginning of HD session were diluted with
      RPMI/heparin and incubated for 24 h in presence of lipopolysaccharide (LPS). IL
      1Gamma, IL-6, TNF-alpha and IL-10 were assayed on supernatants and results were
      normalized per number of lymphomonocytes (ng/106 cells). RESULTS: A depressive
      mood was more frequent in HD patients (50%) than controls (20%, p < 0.0001). No
      difference for anxiety (HD = 43%, controls = 45%) was observed. QOL score was
      significantly lower in HD than controls (p = 0.006) and correlated inversely with
      HADS total, HADS-A and HADS-D (p < 0.0001). Albumin, Kt/V and phosphate were
      comparable in patients with or without anxiety or depression. Cytokine production
      was significantly higher in HD patients than controls (IL-1beta p = 0.05; IL-6 p
      = 0.010; TNF-alpha p < 0.0001; IL-10, p = 0.0019). HD patients with the HADS-A
      positive for anxiety showed higher IL-6 production (p = 0.026), while IL-1beta
      levels were not associated with symptoms of depression. KDQOL-CF correlated
      inversely with levels of IL-6, TNF-alpha and IL-10. CONCLUSIONS: HD patients have
      symptoms of depression and anxiety that negatively affect QOL. These symptoms are
      independent of the efficiency of dialysis and nutritional status. On the
      contrary, IL-6 is linked to the presence of psychological discomfort in these
      patients.

PMID- 20040351
TI  - Relation between polymorphisms of receptor for advanced glycation end products
      (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.
AB  - BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE)
      with advanced glycation end products (AGEs) is an important pathogenic mechanism
      of diabetic complications. Three mutations in the promoter region of the RAGE
      gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides)
      were known to have increased transcriptional activities. We investigated the
      relationship between these polymorphisms and the risk of cardiovascular diseases
      in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type
      2 diabetic subjects with nephropathy were recruited. Genotyping of the three
      polymorphisms in the genomic DNA was done by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8
      years for the development of cardiovascular events and survival. RESULTS: The T
      429 C and T-374 A polymorphism had no effect on the event-free survival of the
      subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0%
      and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank
      test, p = 0.034). After adjusting for confounders, the 63 bp deletion
      polymorphism had a marginal effect on event-free survival (adjusted hazard ratio:
      3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the
      three polymorphisms have significantly higher risk of first ischemic heart
      disease than those with any of the three mutations (adjusted hazard ratio: 0.218,
      95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the
      RAGE gene has a marginal benefit on the cardiovascular event-free survival in
      subjects with diabetic nephropathy. Subjects with any of the three mutations have
      a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of
      cardiovascular disease in diabetic patients requires further study.

PMID- 20040352
TI  - Aminothiols and allantoin in chronic dialysis patients: effects of hemodialysis
      sessions.
AB  - BACKGROUND: To investigate the possible relationship between homocysteine and
      allantoin levels in hemodialyzed patients, serum levels of thiols and purine
      compounds were analyzed before and after dialysis sessions. METHODS: 16
      clinically stable non-diabetic patients hemodialyzed on polysulfone membranes
      were compared with 36 control subjects. Serum samples were collected before and
      after hemodialysis sessions. Total homocysteine, cysteine, glutathione,
      cysteinylglycine, uric acid, hypoxanthine, and allantoin were measured by
      capillary electrophoresis. RESULTS: Pre-dialysis homocysteine, allantoin, and
      uric acid were significantly elevated in dialysis patients as compared to
      controls. Cysteine, glutathione, and hypoxanthine levels were similar in both
      groups. Homocysteine significantly decreased, but did not normalize after
      dialysis sessions. Glutathione and cysteinylglycine levels remained unchanged
      after dialysis sessions, whereas cysteine decreased. Uric acid, hypoxanthine, and
      allantoin levels were significantly reduced by dialysis sessions. The
      allantoin/uric acid ratio was higher in dialyzed patients before hemodialysis
      (0.049 +/- 0.023 vs. 0.016 +/- 0.012 in controls; p < 0.001), and became elevated
      after a dialysis session (0.084 +/- 0.033; p = 0.002). CONCLUSIONS: Despite the
      use of biocompatible membranes, homeostasis of thiols and purine compounds is
      disturbed in hemodialysed patients. We suggest that allantoin could be used as a
      marker for oxidative stress in hemodialyzed patients.

PMID- 20040353
TI  - Evolution of Fabry disease in male patients: the Greek experience.
AB  - Fabry disease is a progressive metabolic disorder with a clinical course
      characterized by different phases and a variety of disease manifestations. The
      first symptoms generally appear in childhood or early adolescence and are
      followed by late life-threatening complications involving vascular, renal,
      cardiac, and cerebral systems. We report the clinical and biochemical
      characteristics of 16 male patients from 10 unrelated families who represent
      almost the entire cohort of known Fabry patients in Greece. Despite the presence
      of early symptoms in almost every patient (mean age at onset of symptoms 15.6
      years), the diagnosis was delayed for a mean of about 18 years (mean age of
      diagnosis 36 years). Patients are currently monitored and the majority (15 out 16
      patients) treated with Enzyme Replacement Therapy.

PMID- 20040354
TI  - Tetanus as a cause of rhabdomyolysis and acute renal failure.
AB  - Acute renal failure developed in an elderly woman with a rapidly progressive
      illness characterized by nuchal rigidity, limb spasm, repetitive grunting
      vocalizations without intelligible speech, and risus sardonicus. Eventually she
      developed characteristic findings of increased tone in her masseter muscles
      (trismus) and rigid upper and lower extremities, consistent with generalized
      tetanus. Increasing serum creatinine was temporally associated with rising
      creatine phosphokinase (CPK) and striking elevations of plasma myoglobin. The
      patient had marked lability of blood pressure and pulse. She improved briefly
      after tetanus toxoid and broad-spectrum antibiotics, but died of heart failure
      after 9 days of hospitalization. A necrotic pelvic tumor was believed to be the
      source of infection. Tetanus is a preventable disease, which has not been
      eradicated, even in Western populations. Full-blown tetanus has a high fatality
      rate, and should be considered in the differential diagnosis of acute renal
      failure in the setting of rising CPK and continued release of muscle myoglobin.

PMID- 20040355
TI  - Tonsillectomy and steroid pulse therapy for recurrent IgA nephropathy in renal
      allograft.
AB  - We experienced two cases of steroid pulse therapy combined with tonsillectomy for
      recurrent IgA nephropathy (IgAN) in a renal allograft. We defined recurrent IgAN
      in renal allograft as IgA deposits in glomeruli with persistent proteinuria (>
      0.5 g/ day) and microscopic hematuria in renal transplant recipients with biopsy
      proven IgAN of their native kidneys. We performed steroid pulse therapy following
      tonsillectomy as therapeutic protocol for recurrent IgAN. The first patient was
      diagnosed with recurrent IgAN by allograft biopsy 3 years after renal
      transplantation, and a second patient was diagnosed after one year. The former
      patient's proteinuria disappeared 4 months after treatment and the latter
      patient's proteinuria disappeared after one month. Tonsillectomy combined with
      steroid pulse therapy can induce clinical remission in patients with recurrent
      IgAN after renal transplantation.

PMID- 20040356
TI  - Successful treatment of refractory septic arthritis caused by salmonella and
      staphylococcus aureus with preservation of graft function in a long-term renal
      transplant recipient by total withdrawal of immunosuppressants.
AB  - An 18-year-old female had received a 2 HLA incompatible renal transplant 10 years
      before. She initially presented with septic arthritis and osteomyelitis caused by
      Salmonella enterica co-infected with Staphylococcus aureus of her left knee with
      development of secondary septic arthritis of the right knee and left shoulder.
      This was complicated by a recurrent subcutaneous abscess and intermittent high
      fever. The infection was successfully treated with a combination of a prolonged
      course of antibiotics, twice joint washout and debridement, repeat aspiration,
      hyperbaric oxygen therapy and a total withdrawal of immunosuppressant resulting
      in good joint function and preservation of normal renal graft function. In our
      experience, it was possible to keep stable renal graft function in spite of
      complete withdrawal of immunosuppressants for 12 months in a recipient with 2 HLA
      mismatches.

PMID- 20040357
TI  - Two cases of Weil's disease with acute renal failure in the central Tokyo
      metropolitan area.
AB  - The incidence of leptospirosis, or Weil's disease, in developed countries,
      particularly in temperate regions, has been dramatically decreasing due to recent
      improvements in the hygienic environment. In these areas, physicians rarely face
      this disease and inclusion as a differential diagnosis of acute renal failure
      seems increasingly uncommon. However, we encountered two cases of severe
      leptospirosis requiring hemodialysis in central Tokyo. Both cases showed
      hyperbilirubinemia, thrombocytopenia and mental disturbance in addition to acute
      renal failure. Severe leptospirosis remains associated with high mortality rates,
      and early clinical suspicion and laboratory confirmation of the disease are
      crucial. Detailed history-taking suggested that leptospirosis was caused by
      transmission from rats in both cases. Rodents inhabit most land areas, implying
      that the disease can occur all over the world, even in huge metropoles such as
      Tokyo. These two cases indicate the need for awareness of leptospirosis among
      physicians working even in urban areas of developed countries.

PMID- 20040358
TI  - Placement of dual lumen non-cuffed dialysis catheter into persistent left
      superior vena cava.

PMID- 20040359
TI  - Identification of a novel compound that inhibits iNOS and COX-2 expression in LPS
      stimulated macrophages from Schisandra chinensis.
AB  - A novel alpha-iso-cubebenol, which has anti-inflammatory effects in
      lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, was isolated from the
      fruits of Schisandra chinensis. alpha-iso-cubebenolinhibited LPS-induced nitric
      oxide (NO) and prostaglandin E(2) (PGE(2)) production. Consistent with these
      findings, alpha-iso-cubebenol also reduced the LPS-induced expression of
      inducible nitric oxide synthase and cyclooxygenase-2 at the protein and mRNA
      levels in a concentration-dependent manner. alpha-iso-cubebenol also inhibited
      LPS-induced nuclear translocation of the NF-kappaB p65 subunit. Furthermore,
      alpha-iso-cubebenol suppressed the phosphorylation of ERK, JNK, and p38 kinase
      induced by LPS. Since the novel alpha-iso-cubebenol blocked the production of
      several pro-inflammatory mediators induced by LPS in macrophages, the molecule
      can be useful material for the development of anti-inflammatory agents against
      bacterial infections or endotoxin.

PMID- 20040360
TI  - Silencing MR-1 attenuates inflammatory damage in mice heart induced by AngII.
AB  - Myofibrillogenesis regulator-1(MR-1) can aggravate cardiac hypertrophy induced by
      angiotensin(Ang) II in mice through activation of NF-kappaB signaling pathway,
      and nuclear transcription factor (NF)-kappaB and activator protein-1(AP-1)
      regulate inflammatory and immune responses by increasing the expression of
      specific inflammatory genes in various tissues including heart. Whether
      inhibition of MR-1 expression will attenuate AngII-induced inflammatory injury in
      mice heart has not been explored. Herein, we monitored the activation of NF
      kappaB and AP-1, together with expression of pro-inflammatory of interleukin(IL)
      6, tumor necrosis factor(TNF)-alpha, vascular-cell adhesion molecule (VCAM)-1,
      platelet endothelial cell adhesion molecule (PECAM), and inflammatory cell
      infiltration in heart of mice which are induced firstly by AngII (PBS),then
      received MR-1-siRNA or control-siRNA injecting. We found that the activation of
      NF-kappaB and AP-1 was inhibited significantly, together with the decreased
      expression of IL-6, TNF-alpha, VCAM-1, and PECAM in AngII-induced mice myocardium
      in MR-1-siRNA injection groups compared with control-siRNA injecting groups.
      However, the expression level of MR-1 was not an apparent change in PBS-infused
      groups than in unoperation groups, and MR-1-siRNA do not affect the expression of
      MR-1 in PBS-infused mice. Our findings suggest that silencing MR-1 protected mice
      myocardium against inflammatory injury induced by AngII by suppression of pro
      inflammatory transcription factors NF-kappaB and AP-1 signaling pathway.

PMID- 20040361
TI  - Activation of PPARdelta up-regulates fatty acid oxidation and energy uncoupling
      genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic beta
      cells.
AB  - Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and
      mitochondrial aberrations contribute to the development of insulin resistance and
      type 2 diabetes. The goal of this study was to investigate the effects of
      peroxisome proliferator-activated receptor delta (PPARdelta) activation on lipid
      oxidation, mitochondrial function, and insulin secretion in pancreatic beta
      cells. After HIT-T15 cells (a beta-cell line) were exposed to high concentrations
      of palmitate and GW501516 (GW; a selective agonist of PPARdelta), we found that
      administration of GW increased the expression of PPARdelta mRNA. GW-induced
      activation of PPARdelta up-regulated carnitine palmitoyltransferase 1 (CPT1),
      long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4),
      and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated
      apoptosis; and reduced basal insulin secretion induced by increased palmitate in
      HIT cells. These results suggest that activation of PPARdelta plays an important
      role in protecting pancreatic beta-cells against aberrations caused by
      lipotoxicity in metabolic syndrome and diabetes.

PMID- 20040362
TI  - Amino acid conditions near the GPI anchor attachment site of prion protein for
      the conversion and the GPI anchoring.
AB  - Prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored protein, and
      the C-terminal GPI anchor signal sequence (GPI-SS) of PrP is cleaved before GPI
      anchoring. However, mutations near the GPI anchor attachment site (the omega
      site) in the GPI-SS have been recognized in human genetic prion diseases.
      Moreover, the omega site of PrP has not been identified except hamster, though it
      is known that amino acid restrictions are very severe at the omega and omega+2
      sites in other GPI-anchored proteins. To investigate the effect of mutations near
      the omega site of PrP on the conversion and the GPI anchoring, and to discover
      the omega site of murine PrP, we systematically created mutant murine PrP with
      all possible single amino acid substitutions at every amino acid residue from
      codon 228 to 240. We transfected them into scrapie-infected mouse neuroblastoma
      cells and examined the conversion efficiencies and the GPI anchoring of each
      mutant PrP. Mutations near the omega site altered the conversion efficiencies and
      the GPI anchoring efficiencies. Especially, amino acid restrictions for the
      conversion and the GPI anchoring were severe at codons 230 and 232 in murine PrP,
      though they were less severe than in other GPI-anchored proteins. Only the mutant
      PrPs presented on a cell surface via a GPI anchor were conversion competent. The
      present study shows that mutations in the GPI-SS can affect the GPI anchoring and
      the conversion efficiency of PrP. We clarified for the first time the omega site
      of murine PrP and the amino acid conditions near the omega site for the
      conversion as well as GPI anchoring.

PMID- 20040363
TI  - Detection of erythrocytes influenced by aging and type 2 diabetes using atomic
      force microscope.
AB  - The pathophysiological changes of erythrocytes are detected at the molecular
      scale, which is important to reveal the onset of diseases. Type 2 diabetes is an
      age-related metabolic disorder with high prevalence in elderly (or old) people.
      Up to now, there are no treatments to cure diabetes. Therefore, early detection
      and the ability to monitor the progression of type 2 diabetes are very important
      for developing effective therapies. Type 2 diabetes is associated with high blood
      glucose in the context of insulin resistance and relative insulin deficiency.
      These abnormalities may disturb the architecture and functions of erythrocytes at
      molecular scale. In this study, the aging- and diabetes-induced changes in
      morphological and biomechanical properties of erythrocytes are clearly
      characterized at nanometer scale using atomic force microscope (AFM). The
      structural information and mechanical properties of the cell surface membranes of
      erythrocytes are very important indicators for determining the healthy, diseased
      or aging status. So, AFM may potentially be developed into a powerful tool in
      diagnosing diseases.

PMID- 20040364
TI  - Analysis of supercooling-facilitating (anti-ice nucleation) activity of flavonol
      glycosides.
AB  - Deep supercooling xylem parenchyma cells (XPCs) of katsura tree (Cercidiphyllum
      japonicum) contain four kinds of flavonol glycosides with high supercooling
      facilitating (anti-ice nucleation) activities. These flavonol glycosides have
      very similar structures, but their supercooling-facilitating activities are very
      different. In this study, we analyzed the supercooling-facilitating activities of
      12 kinds of flavonol glycosides in order to determine the chemical structures
      that might affect supercooling-facilitating activity. All of the flavonol
      glycosides tested showed supercooling-facilitating activity, although the
      magnitudes of activity differed among the compounds. It was clear that the
      combination of the position of attachment of the glycosyl moiety, the kind of
      attached glycosyl moiety and the structure of aglycone determined the magnitude
      of anti-ice nucleation activity. However, there is still some ambiguity
      preventing the exact identification of features that affect the magnitude of
      supercooling-facilitating activity.

PMID- 20040365
TI  - Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome
      systems.
AB  - The ubiquitin proteasome system (UPS) and macroautophagy (hereafter called
      autophagy) were, for a long time, regarded as independent degradative pathways
      with few or no points of interaction. This view started to change recently, in
      the light of findings that have suggested that ubiquitylation can target
      substrates for degradation via both pathways. Moreover, perturbations in the flux
      through either pathway have been reported to affect the activity of the other
      system, and a number of mechanisms have been proposed to rationalise the link
      between the UPS and autophagy. Here we critically review these findings and
      outline some outstanding issues that still await clarification.

PMID- 20040366
TI  - Resveratrol preconditioning induces cellular stress proteins and is mediated via
      NMDA and estrogen receptors.
AB  - Resveratrol pretreatment has been shown to provide neuroprotection in models of
      cerebral ischemia. This phenomenon, commonly termed preconditioning, promotes
      ischemic tolerance and may involve mild activation of endoplasmic reticulum
      stress pathways in the affected tissue. Systemic injection of resveratrol (2 x
      10(-3), 2 x 10(-4), 1 x 10(-4) mg/kg) 30 min prior to a 4 h period of right
      middle cerebral artery occlusion significantly reduced infarct area in the
      insular region of rat prefrontal cortex. This affect was blocked when resveratrol
      treatment was combined with a non-selective estrogen receptor antagonist, or
      preceded by intracortical injection of an NMDA receptor antagonist. The
      neuroprotective effect of resveratrol was associated with reduced renal
      sympathetic nerve activity as well as induction of resident endoplasmic reticulum
      chaperone proteins, glucose-regulated proteins 78 and 94. The calcium-sensitive
      chaperone heat shock protein 70 and the cysteine protease m calpain did not
      respond to resveratrol pretreatment. However, a significant induction of heat
      shock protein 70 was observed in the contralateral cortex of resveratrol
      pretreated rats following 4 h of right middle cerebral artery occlusion. These
      data suggest that resveratrol preconditioning promotes ischemic tolerance in the
      short term, in part via effects mediated through activation of estrogen and NMDA
      receptors, as well as through mild activation of cellular stress proteins.

PMID- 20040367
TI  - The forkhead transcription factors, Foxp1 and Foxp2, identify different
      subpopulations of projection neurons in the mouse cerebral cortex.
AB  - Foxp1 and Foxp2, which belong to the forkhead transcription factor family, are
      expressed in the developing and adult mouse brain, including the striatum,
      thalamus, and cerebral cortex. Recent reports suggest that FOXP1 and FOXP2 are
      involved in the development of speech and language in humans. Although both Foxp1
      and Foxp2 are expressed in the neural circuits that mediate speech and language,
      including the corticostriatal circuit, the functions of Foxp1 and Foxp2 in the
      cerebral cortex remain unclear. To gain insight into the functions of Foxp1 and
      Foxp2 in the cerebral cortex, we characterized Foxp1- and Foxp2-expressing cells
      in postnatal and adult mice using immunohistochemistry. In adult mice, Foxp1 was
      expressed in neurons of layers III-VIa in the neocortex, whereas the expression
      of Foxp2 was restricted to dopamine and cyclic adenosine 3',5'-monophosphate
      regulated phosphoprotein, 32 kDa (DARPP-32)(+) neurons of layer VI. In addition,
      Foxp2 was weakly expressed in the neurons of layer V of the motor cortex and
      hindlimb and forelimb regions of the primary somatosensory cortex. Both Foxp1 and
      Foxp2 were expressed in the ionotropic glutamate receptor (GluR) 2/3(+) neurons,
      and colocalized with none of GluR1, gamma-aminobutyric acid, calbindin, and
      parvalbumin, indicating that expression of Foxp1 and Foxp2 is restricted to
      projection neurons. During the postnatal stages, Foxp1 was predominantly
      expressed in Satb2(+)/Ctip2(-) corticocortical projection neurons of layers III-V
      and in Tbr1(+) corticothalamic projection neurons of layer VIa. Although Foxp2
      was also expressed in Tbr1(+) corticothalamic projection neurons of layer VI, no
      colocalization of Foxp1 with Foxp2 was observed from postnatal day (P) 0 to P7.
      These findings suggest that Foxp1 and Foxp2 may be involved in the development of
      different cortical projection neurons during the early postnatal stages in
      addition to the establishment and maintenance of different cortical circuits from
      the late postnatal stage to adulthood.

PMID- 20040368
TI  - Simvastatin enhances hippocampal long-term potentiation in C57BL/6 mice.
AB  - Statins inhibit 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting
      enzyme in the cholesterol biosynthetic pathway, and they are widely used to
      control plasma cholesterol levels and prevent cardiovascular disease. However,
      emerging evidence indicates that the beneficial effects of statins extend to the
      CNS. Statins have been shown to improve the outcome of stroke and traumatic brain
      injury, and statin use has been associated with a reduced prevalence of
      Alzheimer's disease (AD) and dementia. However, prospective studies with statins
      in AD have produced mixed results. Recently, we reported that simvastatin, a
      widely used statin in humans, enhances learning and memory in non-transgenic mice
      as well as in transgenic mice with AD-like pathology on a mixed genetic
      background. However, the cellular and molecular mechanisms underlying the
      beneficial effects of simvastatin on learning and memory remain elusive. The
      present study was undertaken to investigate the effect of acute simvastatin
      treatment on hippocampal long-term potentiation (LTP), a cellular model of
      learning and memory, in brain slices from C57BL/6 mice. Our results demonstrate
      that a prolonged in vitro simvastatin treatment for 2-4 h, but not a short-term
      20-min exposure, significantly increases the magnitude of LTP at CA3-CA1 synapses
      without altering basal synaptic transmission or the paired-pulse facilitation
      ratio in hippocampal slices. Furthermore, we show that phosphorylation of Akt
      (protein kinase B) is increased significantly in the CA1 region following 2-hour
      treatment with simvastatin, and that inhibition of Akt phosphorylation suppresses
      the simvastatin-induced enhancement of LTP. These findings suggest activation of
      Akt as a molecular pathway for augmented hippocampal LTP by simvastatin
      treatment, and implicate enhancement of hippocampal LTP as a potential cellular
      mechanism underlying the beneficial effects of simvastatin on cognitive function.

PMID- 20040369
TI  - Involvement of caspase and MAPK activities in norcantharidin-induced colorectal
      cancer cell apoptosis.
AB  - Norcantharidin exhibits cytotoxicity in many cancer cell lines, including
      colorectal cancer (CRC) cells. Its cytotoxic potency on primary CRC cells and
      other normal constituent cells of the human body remains elusive. This study
      investigates whether norcantharidin differentially exhibits cytotoxicity on
      primarily isolated CRC cells and dermal fibroblasts. The in vitro
      chemosensitivity of norcantharidin was measured using a MTT tetrazolium assay and
      compared with 73 primary tumor cells from surgically excised colorectal tumors,
      six human CRC cell lines and dermal fibroblasts. Observations of cytotoxicity to
      primary tumor cells reveal significant differences among genders and histological
      types; however, drug-induced chemosensitivity was not correlated with age or
      clinical stages of CRC patients. Norcantharidin had a similar cytotoxic effect on
      primary tumor cells and CRC cell lines in a dose-dependent manner. In contrast,
      normal fibroblasts were more resistant to norcantharidin-induced cytotoxicity
      than CRC cells. DAPI staining results demonstrated that norcantharidin caused CRC
      cell apoptosis by nuclear fragmentation and chromatin condensation. The release
      of cytochrome c and the triggering of caspase-3, -8 and -9 activation mediated
      apoptotic induction. Conversely, pretreatment with caspases or mitogen-activated
      protein kinase (MAPK) inhibitors significantly suppressed norcantharidin-induced
      CRC cytotoxicity. These in vitro results suggest that norcantharidin may be a
      safe and effective anti-cancer drug for CRC.

PMID- 20040370
TI  - Protective effects of standardized Thuja orientalis leaves against 6
      hydroxydopamine-induced neurotoxicity in SH-SY5Y cells.
AB  - Although the etiology of Parkinson's disease (PD) remains unknown, recent studies
      have suggested that oxidative stress (OS) and apoptosis, as a result of
      mitochondrial defects, may play important roles in its pathogenesis. 6
      Hydroxydopamine (6-OHDA), a neurotoxin commonly used in models of PD, induces
      selective catecholaminergic cell death, mediated by reactive oxygen species (ROS)
      and mitochondrial defects. This study investigated the protective effect of Thuja
      orientalis leaves (TOFE), a well-known oriental traditional medicine, on 6-OHDA
      induced neurotoxicity in SH-SY5Y cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay and Hoechst staining showed that TOFE
      attenuated the cell damage caused by 6-OHDA stress. TOFE showed strong radical
      scavenging effects in 2,2-diphenyl-2-picrylhydrazyl and 2,2-azinobis-(3-ethyl
      benzthiazoline-6-sulphonic acid) assays, and it reduced the intracellular ROS and
      extracellular nitric oxide production induced by 6-OHDA. Additionally, TOFE
      blocked the reduction in the mitochondrial membrane potential, the release of
      cytochrome c, and the activation of caspase-3. Moreover, TOFE decreased the
      phosphorylation of extracellular signal-regulated kinase (pERK), which has pro
      apoptotic functions. Taken together, TOFE might protect SH-SY5Y cells from 6-OHDA
      through the downregulation of OS and mitochondrial-mediated apoptosis, and
      regulation of pERK.

PMID- 20040371
TI  - Isoliquiritigenin 2'-methyl ether induces growth inhibition and apoptosis in oral
      cancer cells via heme oxygenase-1.
AB  - We previously reported that a chloroform extract of Caesalpinia sappan L. induces
      apoptosis in oral cancer cells but not in normal epithelial cell lines. In the
      present study, we explored the effects of a single compound isolated from C.
      sappan heartwood, isoliquiritigenin 2'-methyl ether (ILME), on cultured primary
      and metastatic oral cancer cell lines using MTT assays, fluorescence microscopy,
      flow cytometry, and Western blotting. ILME inhibited the growth of the oral
      cancer cells in a time- and dose-dependent manner. The major mechanism of growth
      inhibition was apoptosis induction, as shown by flow cytometric analysis of sub
      G(1)-phase arrest and by annexin V-FITC and propidium iodide staining. ILME time
      dependently activated NF-kappaB transcription factors, phospholated the MAP
      kinases JNK (c-Jun N-terminal kinase) and ERK (extracellular signal-regulated
      kinase). Furthermore, ILME treatment upregulated HO-1 expression though
      activation of Nrf2 (NF-E2-related factor 2) pathway, and induced the expression
      of heme oxygenase-1 (HO-1). Tin protoporphyrin, an HO-1 inhibitor, dose
      dependently attenuated the growth-inhibitory effect of ILME and blocked ILME
      induced expression of the p21 and p53 cell cycle-regulatory proteins. These
      results provide the first evidence that the anti-oral cancer effects of ILME may
      involve a mechanism in which HO-1 is upregulated via a pathway involving MAP
      kinases, NF-kappaB, and Nrf2. Thus, ILME could be considered to be a potential
      chemotherapeutic target for anti-oral cancer treatment strategies.

PMID- 20040372
TI  - The mitogen-activated protein kinase p38 is involved in insect defense against
      Cry toxins from Bacillus thuringiensis.
AB  - The insecticidal Cry toxins are pore-forming toxins produced by the bacteria
      Bacillus thuringiensis that disrupt insect-midgut cells. In this work we analyzed
      the response of two different insect orders, the Lepidopteran Manduca sexta and
      Dipteran Aedes aegypti to highly specific Cry toxins, Cry1Ab and Cry11Aa,
      respectively. One pathway activated in different organisms in response to a
      variety of pore-forming toxins is the mitogen-activated protein kinase p38
      pathway (MAPK p38) that activates a complex defense response. We analyzed the
      MAPK p38 activation by immunodetection of its phosphorylated isoform, and the
      induction of p38 by RT-PCR, real-time PCR quantitative assays and
      immunodetection. We show that MAPK p38 is activated at postraductional level
      after Cry toxin intoxication in both insect orders. We detected the p38 induction
      at the transcriptional and traductional level, and observed a different response.
      In these three levels, we found that both insects respond to Cry toxin action but
      M. sexta responses more strongly than A. aegypti. Gene silencing of MAPK p38 in
      vivo, resulted in both insect species becoming hypersensitive to Cry toxin
      action, suggesting that the MAPK p38 pathway is involved in insect defense
      against Bt Cry toxins. This finding may have biotechnological applications for
      enhancing the activity of some Bt Cry toxins against specific insect pests.

PMID- 20040373
TI  - GATA transcription, translation and regulation in Haemaphysalis longicornis tick:
      analysis of the cDNA and an essential role for vitellogenesis.
AB  - Blood feeding tightly regulates the reproductive cycles of ticks. Vitellogenesis
      and nutritional signaling are key events in the tick reproductive cycle. Here we
      report the identification of a GATA factor that is synthesized after a blood meal
      and acts as a transcriptional activator of vitellogenin (Vg), and the
      identification of an S6 kinase that is a transcription regulator of the amino
      acid signaling pathway. Tick GATA mRNA accumulated in the midgut prior to blood
      feeding. However, translation of GATA was activated by blood feeding because the
      GATA protein dramatically increased in the fat body of engorged females. RNA
      interference-mediated knockdown of S6 kinase and GATA factor revealed the
      involvements of S6 kinase in GATA activation and resulted in a significant
      inhibition of the major yolk protein vitellogenin in engorged ticks and
      effectively disrupting egg development after a blood meal. These results indicate
      that the GATA factor, a specific transcriptional activator of Vg gene, represents
      an important molecule for the regulation of tick vitellogenesis and reproduction.

PMID- 20040374
TI  - Catechol 1,2-dioxygenase from the Gram-positive Rhodococcus opacus 1CP:
      quantitative structure/activity relationship and the crystal structures of native
      enzyme and catechols adducts.
AB  - The first crystallographic structures of a catechol 1,2-dioxygenase from a Gram
      positive bacterium Rhodococcus opacus 1CP (Rho 1,2-CTD), a Fe(III) ion containing
      enzyme specialized in the aerobic biodegradation of catechols, and its adducts
      with catechol, 3-methylcatechol, 4-methylcatechol, pyrogallol (benzene-1,2,3
      triol), 3-chlorocatechol, 4-chlorocatechol, 3,5-dichlorocatechol, 4,5
      dichlorocatechol and protocatechuate (3,4-dihydroxybenzoate) have been determined
      and analyzed. This study represents the first extensive characterization of
      catechols adducts of 1,2-CTDs. The structural analyses reveal the diverse modes
      of binding to the active metal iron ion of the tested catechols thus allowing to
      identify the residues selectively involved in recognition of the diverse
      substrates by this class of enzymes. The comparison is further extended to the
      structural and functional characteristics of the other 1,2-CTDs isolated from
      Gram-positive and Gram-negative bacteria. Moreover the high structural homology
      of the present enzyme with the 3-chlorocatechol 1,2-dioxygenase from the same
      bacterium are discussed in terms of their different substrate specificity. The
      catalytic rates for Rho 1,2-CTD conversion of the tested compounds are also
      compared with the calculated energies of the highest occupied molecular orbital
      (E(HOMO)) of the substrates. A quantitative relationship (R=0.966) between the ln
      k(cat) and the calculated electronic parameter E(HOMO) was obtained for catechol,
      3-methylcatechol, 4-methylcatechol, pyrogallol, 3-chlorocatechol, 4
      chlorocatechol. This indicates that for these substrates the rate-limiting step
      of the reaction cycle is dependent on their nucleophilic reactivity. The
      discrepancies observed in the quantitative relationship for 3,5-dichlorocatechol,
      4,5-dichlorocatechol and protocatechuate are ascribed to the sterical hindrances
      leading to the distorted binding of such catechols observed in the corresponding
      structures.

PMID- 20040375
TI  - Hennig's orphans revisited: testing morphological hypotheses in the "Opomyzoidea"
      (Diptera: Schizophora).
AB  - The acalyptrate fly superfamily Opomyzoidea, as currently recognized, is a poorly
      known group of 14 families. The composition of this group and relationships among
      included families have been controversial. Furthermore, the delimitation of two
      opomyzoid families, Aulacigastridae and Periscelididae, has been unstable with
      respect to placement of the genera Stenomicra, Cyamops, and Planinasus. To test
      the monophyly of Opomyzoidea, previously proposed relationships between families,
      and the position of the three problematic genera, we sequenced over 3300bp of
      nucleotide sequence data from the 28S ribosomal DNA and CAD (rudimentary) genes
      from 29 taxa representing all opomyzoid families, as well as 13 outgroup taxa.
      Relationships recovered differed between analyses, and only branches supporting
      well-established monophyletic families were recovered with high support, with a
      few exceptions. Opomyzoidea and its included subgroup, Asteioinea, were found to
      be non-monophyletic. Stenomicra, Cyamops, and Planinasus group consistently with
      Aulacigastridae, contrary to recent classifications. Xenasteiidae and
      Australimyzidae, two small, monogeneric families placed in separate
      superfamilies, were strongly supported as sister groups.

PMID- 20040376
TI  - Molecular phylogenetics of North American phoxinins (Actinopterygii:
      Cypriniformes: Leuciscidae) based on RAG1 and S7 nuclear DNA sequence data.
AB  - Most molecular phylogenetic hypotheses for North American (NA) phoxinins are
      based on mitochondrial DNA sequences (mtDNA) and the resulting hypotheses are
      rather variable, though there is general support for three major lineages of NA
      phoxinins: western, creek chub-plagopterin (CC-P), and open posterior myodome
      (OPM) clades. Support for a monophyletic NA phoxinin group has varied among
      studies. This study utilizes nuclear DNA (nDNA) sequences from the RAG1 (exon 3)
      and S7 (intron 1) gene regions to evaluate the phylogenetic relationships and
      monophyly of NA phoxinins. Results from the nDNA analyses provide overall support
      for the western, CC-P, and OPM clades. The CC-P clade had the best overall
      resolution and support in the individual and combined analyses of the nDNA data.
      Resolution of the western clade was fairly good, with most analyses recovering a
      monophyletic Gila clade. The OPM clade demonstrated the highest degree of
      topological variability among the analyses. The RAG1 analyses failed to recover a
      monophyletic NA phoxinin group by resolving the European leuciscins, inclusive
      Notemigonus crysoleucas, within the NA phoxinin topology. Most analyses recovered
      a strongly supported shiner clade though, similar to several mtDNA studies; there
      was a high degree of topological variability among the results.

PMID- 20040377
TI  - Phylogeny of the bristle worm family Eunicidae (Eunicida, Annelida) and the
      phylogenetic utility of noncongruent 16S, COI and 18S in combined analyses.
AB  - The bristleworm family Eunicidae is distributed worldwide and well-known for the
      large size of many of its species, its hard jaws and its economic importance in
      the bait industry. Monophyly of Eunicidae has been contradicted in previous
      molecular and morphological phylogenetic analyses focusing on Eunicida or on its
      type genus, Eunice. The current study focused on the phylogeny of the family per
      se combining mitochondrial and nuclear genes in different analyses. It recovered
      well-resolved phylogenetic hypotheses supporting the monophyly of Eunicidae and
      Palola, the only monophyletic genus among the genera for which we tested their
      monophyly (Eunice, Marphysa, Palola, Lysidice and Nematonereis). Four other
      stable clades containing the type species of different genera, or species deemed
      very similar to them, were recovered within Eunicidae. These clades may represent
      monophyletic redefinitions of current genera, except for Eunice, and of previous
      synonymized genera. Evolution of the number of peristomial cirri and prostomial
      appendages in Eunicidae happened by independent step-by-step reduction in the
      opposite order of their ontogenetic development, suggestive of sequential
      heterochrony. All three genes were informative, however, at different levels
      within the combined trees. 16S and COI were important in recovering a
      monophyletic Eunicidae and relationships within the family, while 18S was
      important in the resolution of basal eunicidan relationships, monophyly of
      Onuphidae and basal relationships within this family. Moreover, results of
      congruence tests (SH and WRST using PABA) indicate that hidden support is picked
      up in the combined analyses, which is not revealed in the single gene analyses.
      Further supporting the idea that congruence is not a requirement for combining
      different partitions.

PMID- 20040378
TI  - Taxonomic position of Eunapius subterraneus (Porifera, Spongillidae) inferred
      from molecular data--a revised classification needed?
AB  - The freshwater sponge Eunapius subterraneus was described in 1984 on the basis of
      its morphology and unique ecological features. It inhabits caves in the Ogulin
      karst area as the only known stygobitic sponge, and an endangered karst species.
      We used three genetic markers with different evolutionary rates in phylogenetic
      analyses of E. subterraneus. All of the markers exclude this sponge from the
      genus Eunapius. Based on our results, we emphasize the need for revision of the
      taxonomic classification of E. subterraneus as well as the need for a thorough re
      evaluation of freshwater sponge systematics.

PMID- 20040379
TI  - Speciation dynamics in the SE Asian tropics: Putting a time perspective on the
      phylogeny and biogeography of Sundaland tree squirrels, Sundasciurus.
AB  - Tropical rainforests are well known for their extraordinarily high levels of
      biodiversity. The origin of this species richness is still debated. For instance,
      the museum hypothesis states that over evolutionary time more and more species
      will accumulate with relatively few extinctions. In contrast, the Pleistocene
      diversification model argues that during the last 2 million years, climatic
      factors (glaciations) caused environmental changes that drove isolation and
      vicariant speciation events. In this study, we construct a molecular phylogeny of
      the Sundaland (Malay Peninsula, Sumata, Borneo, Palawan) and Greater Mindanao
      (Mindanao, Samar, Leyte) tree squirrels (genus Sundasciurus). Our results show
      that most speciation events in this forest dependent taxon occurred before the
      Pleistocene and that even the timing of intra-specific splits among populations
      from different landmasses are relatively old. Additionally, we found unexpectedly
      high divergence within and between highland populations of S. tenuis on Sumatra
      and the Malay Peninsula, highlighting the importance of Pliocene events in both
      speciation and within species divergences in this region.

PMID- 20040380
TI  - Influence of cholesterol and fish oil dietary intake on nitric oxide-induced
      apoptosis in vascular smooth muscle cells.
AB  - Apoptosis of vascular smooth muscle cells (SMC) is critically involved in the
      progression of atherosclerosis. We previously reported that dietary cholesterol
      intake induces changes in SMC at molecular and gene expression levels. The
      objectives of the present study were to investigate the differential response to
      nitric oxide of vascular SMC obtained from chicks after cholesterol and fish oil
      dietary intake and to examine effects on the main pro-apoptotic and anti
      apoptotic genes. Dietary cholesterol intake reduced the Bcl-2/Bax (anti
      apoptotic/pro-apoptotic) protein ratio in SMC, making them more susceptible to
      apoptosis. When cholesterol was withdrawn and replaced with a fish oil-enriched
      diet, the Bcl-xl/Bax protein ratio significantly increased, reversing the changes
      induced by cholesterol. The decrease in c-myc gene expression after apoptotic
      stimuli and the increase in Bcl-xl/Bax ratio indicate that fish oil has a
      protective role against apoptosis in SMC. Nitroprussiate-like nitric oxide donors
      exerted an intensive action on vascular SMC cultures. However, SMC-C (isolated
      from animals fed with control diet) and SMC-Ch (isolated from animals fed with
      cholesterol-enriched diet) responded differently to nitric oxide, especially in
      their bcl-2 and bcl-xl gene expression. SMC isolated from animals fed with
      cholesterol-enriched and then fish oil-enriched diet (SMC-Ch-FO cultures) showed
      an intermediate apoptosis level (Bcl-2/Bax ratio) between SMC-C and SMC-Ch,
      induction of c-myc expression and elevated p53 expression. These findings
      indicate that fish oil protects SMC against apoptosis.

PMID- 20040381
TI  - Asymmetric dimethylarginine (ADMA) is present in plasma proteins of healthy
      subjects at the low nmol-per-g-level.

PMID- 20040382
TI  - Somatic DNA alterations in lung epithelial barrier cells in COPD patients.
AB  - BACKGROUND: Instability of the Microsatellite DNA Instability (MSI) and Loss of
      Heterozygosity (LOH) have been previously detected in sputum cells of COPD
      patients. However, the particular cell subpopulation exhibiting genetic
      instability in COPD was uncertain. The aim of this study was to determine which
      cell type expresses Microsatellite DNA Instability in sputum and BALF samples
      from COPD patients. METHODS: Thirty-five COPD patients and 30 non-COPD smokers
      were studied. Sputum was induced from 20 COPD patients and 20 non-COPD smokers
      and BALF was obtained from 15 COPD patients and 10 non-COPD smokers. The sputum
      cell pellet and BALF samples were processed using immunomagnetic technology to
      separate antibody-specific cell subpopulations, using CD45+ for leukocytes,
      Epithelial enrich (MACS) for sputum epithelial cells and HEA-human epithelial
      antigen-(Dynal) for BAL epithelial cells. Microsatellite DNA amplification was
      performed using specific primers, namely G29802, D6S2223, D6S344, D6S263, D5S207,
      D13S71, RH70958, and D17S250. The presence of MSI and/or LOH was analyzed with LI
      COR Saga GT Microsatellite Analysis Software. MEASUREMENTS AND MAIN RESULTS: None
      of the non-COPD smokers exhibited any genetic alteration. MSI and LOH were found
      in 15 cases (8 MSI and 7 LOH) in sputum and BAL samples. MSI and/or LOH were
      revealed only in the epithelial barrier cells. LOH was detected in D5S207,
      D6S344, G29802 and D17S250 microsatellite markers, while MSI in D13S71, D5S207
      and D6S344. The entire leukocyte subpopulation exhibited no genetic alteration.
      CONCLUSIONS: Our results support the hypothesis that chronic inflammation and
      oxidative burden in COPD can lead to DNA damage of the lung epithelial barrier
      cells, detected at the Microsatellite DNA level. Further studies are required to
      investigate the significance of these findings in the pathogenesis of COPD.

PMID- 20040383
TI  - Early abnormalities of post-sigh breathing in a mouse model of Rett syndrome.
AB  - Rett syndrome is a neurodevelopmental disease accompanied by complex, disabling
      symptoms, including breathing symptoms. Because Rett syndrome is caused by
      mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2),
      Mecp2-deficient mice have been generated as experimental model. Males of Mecp2
      deficient mice (Mecp2(-/y)) breathe normally at birth but show abnormal
      respiratory responses to hypoxia and hypercapnia from postnatal day 25 (P25).
      After P30, Mecp2(-/y) mice develop breathing symptoms reminiscent of Rett
      syndrome, aggravating until premature death at around P60. Using plethysmography,
      we analyzed the sighs and the post-sigh breathing pattern of unrestrained wild
      type male mice (WT) and Mecp2(-/y) mice from P15 to P60. Sighs are spontaneous
      large inspirations known to prevent lung atelectasis and to improve alveolar
      oxygenation. However, Mecp2(-/y) mice show early abnormalities of post-sigh
      breathing, with long-lasting post-sigh apnoeas, reduced tidal volume when eupnoea
      resumes and lack of post-sigh bradypnoea which develop from P15, aggravate with
      age and possibly contribute to breathing symptoms to come.

PMID- 20040384
TI  - Ionic substitutions in calcium phosphates synthesized at low temperature.
AB  - Ionic substitutions have been proposed as a tool to improve the biological
      performance of calcium phosphate based materials. This review provides an
      overview of the recent results achieved on ion-substituted calcium phosphates
      prepared at low temperature, i.e. by direct synthesis in aqueous medium or
      through hydrolysis of more soluble calcium phosphates. Particular attention is
      focused on several ions, including Si, Sr, Mg, Zn and Mn, which are attracting
      increasing interest for their possible biological role, and on the recent trends
      and developments in the applications of ion-substituted calcium phosphates in the
      biomedical field.

PMID- 20040385
TI  - Biodegradable microgrooved polymeric surfaces obtained by photolithography for
      skeletal muscle cell orientation and myotube development.
AB  - During tissue formation, skeletal muscle precursor cells fuse together to form
      multinucleated myotubes. To understand this mechanism, in vitro systems promoting
      cell alignment need to be developed; for this purpose, micrometer-scale features
      obtained on substrate surfaces by photolithography can be used to control and
      affect cell behaviour. This work was aimed at investigating how differently
      microgrooved polymeric surfaces can affect myoblast alignment, fusion and myotube
      formation in vitro. Microgrooved polymeric films were obtained by solvent casting
      of a biodegradable poly-l-lactide/trimethylene carbonate copolymer (PLLA-TMC)
      onto microgrooved silicon wafers with different groove widths (5, 10, 25, 50,
      100microm) and depths (0.5, 1, 2.5, 5microm), obtained by a standard
      photolithographic technique. The surface topography of wafers and films was
      evaluated by scanning electron microscopy. Cell assays were performed using C2C12
      cells and myotube formation was analysed by immunofluorescence assays. Cell
      alignment and circularity were also evaluated using ImageJ software. The obtained
      results confirm the ability of microgrooved surfaces to influence myotube
      formation and alignment; in addition, they represent a novel further improvement
      to the comprehension of best features to be used. The most encouraging results
      were observed in the case of microstructured PLLA-TMC films with grooves of 2.5
      and 1microm depth, presenting, in particular, a groove width of 50 and 25microm.

PMID- 20040386
TI  - Synthesis of novel celluloses derivatives and investigation of their mitogenic
      activity in the presence and absence of FGF2.
AB  - Novel cellulose sulfates (CS) with a controlled degree of sulfation (DS(S)) were
      synthesized through acetosulfation as well as direct sulfation. CS containing
      carboxyl (CO) or carboxymethyl (CM) groups were prepared by TEMPO oxidation or by
      carboxymethylation with chloroacetic acid. The derivatization was characterized
      by nuclear magnetic resonance and Raman spectroscopy. The derivatives were
      investigated regarding their cytotoxicity and mitogenic activity by modulation of
      3T3 fibroblast proliferation with or without exogenous FGF2. All derivatives were
      non-toxic for 3T3 cells. CS strongly promoted FGF2-induced proliferation, which
      was positively related to overall DS(S). In the absence of FGF2, minute
      quantities of CS with intermediate degrees of sulfation exerted stronger
      mitogenic effects than heparin. No significant promoting effects of CO and CM on
      cell proliferation were found, though the structure of CO shows similarities to
      heparin.

PMID- 20040387
TI  - Effects of crystalline phase on the biological properties of collagen
      hydroxyapatite composites.
AB  - The objective of this study was to investigate the effects of spatial structure
      and crystalline phase on the biological performance of collagen-hydroxyapatite
      (Col-HA) composite prepared by biomineralization crystallization. Two types of
      Col-HA composites were prepared using mineralization crystallization (MC
      composites) and pre-crystallization (PC composites), respectively. Structural
      characteristics were analyzed by scanning electron microscopy and transmission
      electron microscopy. Surface elemental compositions were measured by electron
      spectroscopy for chemical analysis (ESCA). These composites were used in in vivo
      repair of bone defects. The effects of the crystalline phase on the biological
      performance of Col-HA composites were investigated using radionuclide bone scan,
      histopathology and morphological observation. It was observed that in MC
      composites, HA was located on the surface of the collagen fibers and aggregated
      into crystal balls, whereas HA in PC composites was scattered among the collagen
      fibers. ESCA showed that phosphorus and calcium were 8.99% and 17.56% on MC
      composite surface, compared with 4.39% and 5.86% on the PC composite surface. In
      vivo bone defect repair experiments revealed that radionuclide uptake was
      significantly higher in the area implanted with the PC composite than in the
      contralateral area implanted with the MC composite. Throughout the whole repair
      process, the PC composite proved to be superior to the MC composite with regard
      to capillary-forming capacity and the amount of newly formed bone tissue. So it
      could be concluded that HA placement on collagen fibers affected the biological
      performance of Col-HA composites. Pre-crystallization made HA scattered among
      collagen fibers, creating a better structure for bone defect repair in comparison
      with MC Col-HA composites.

PMID- 20040388
TI  - The use of air plasma in surface modification of peripheral nerve conduits.
AB  - Surface modification is a conventional approach in biomaterials development, but
      most of the modification processes are intricate and time inefficient. In this
      study, a convenient open air plasma treatment was employed to modify the surface
      of poly(d,l-lactide) (PLA). Chitosan and fibroblast growth factor 1 (FGF1) were
      sequentially grafted with the assistance of open air plasma treatment onto the
      PLA nerve conduits with designed micropores and surface microgrooves. Grafting of
      these components was verified by electron spectroscopy for chemical analysis. The
      modified nerve conduits showed enhanced ability in the repair of 10-mm sciatic
      nerve transection defects in rats. The sequential air plasma treatment can be a
      convenient way to introduce biocompatible (e.g., chitosan) and bioactive
      components (e.g., growth factors) onto the surface of biomaterials.

PMID- 20040389
TI  - Flavones suppress type I IL-4 receptor signaling by down-regulating the
      expression of common gamma chain.
AB  - Immunoglobulin E (IgE) production is induced by interleukin (IL)-4 signaling
      mediated by type I IL-4 receptor (IL-4R) in B cells. We found that flavones
      inhibited IL-4-induced epsilon germline transcription which is essential for IgE
      class switching, and the phosphorylation of signal transducer and activator of
      transcription 6, janus kinase 3, and IL-4Ralpha, whereas IL-4 signaling mediated
      through type II IL-4R was unaffected by flavones. Furthermore, flavones reduced
      the expression of common gamma chain, a characteristic constituent subunit of
      type I IL-4R, suggesting that flavones suppress type I IL-4R signaling.

PMID- 20040390
TI  - Cerebral phaeohyphomycosis in a green iguana (Iguana iguana).
AB  - Cerebral phaeohyphomycosis was diagnosed in a 4-year-old green iguana (Iguana
      iguana) with paroxysmal spastic paralysis of all limbs and circling motion.
      Formalin-fixed tissues were collected at necropsy examination and submitted for
      evaluation. The left cerebrum and the left ventricle were replaced by a solid
      brown coloured mass. Microscopical examination revealed the presence of
      necrotizing and granulomatous encephalitis affecting the cerebrum, cerebellum and
      brainstem, with severe vasculitis and intralesional dematiaceous fungal hyphae.
      No other lesions or fungi were found in other organs. Fungi were identified as
      Oidiodendron spp. by sequence analysis of the internal transcribed spacer (ITS)
      region 1 extracted from formalin-fixed and paraffin wax-embedded brain tissue.
      This case represents the first report of phaeohyphomycosis with tropism for the
      central nervous system in a reptile. In the absence of fresh tissue, the
      diagnosis in such cases may be assisted by molecular analysis of fixed tissue
      specimens.

PMID- 20040392
TI  - Epidermal growth factor receptor and HER-2/neu status by immunohistochemistry and
      fluorescence in situ hybridization in adenocarcinomas of the biliary tree and
      gallbladder.
AB  - Adenocarcinomas of the biliary tract and gallbladder are aggressive tumors with a
      poor prognosis. Standard chemotherapy often offers minimal benefit. Because
      epidermal growth factor receptor and HER-2/neu antagonists have been successfully
      used in adenocarcinomas from other sites, their use in cholangiocarcinoma can be
      potentially beneficial. This study examines the epidermal growth factor receptor
      and HER-2/neu expression and the epidermal growth factor receptor gene copy
      number in biliary tract adenocarcinomas. Fifty-one formalin-fixed, paraffin
      embedded cases of adenocarcinomas (26 intrahepatic, 19 extrahepatic, 6
      gallbladder) were stained with monoclonal antibodies against epidermal growth
      factor receptor and HER-2/neu. Fluorescence in situ hybridization analysis was
      performed in 37 cases using probes directed against epidermal growth factor
      receptor and centromeric region of chromosome 7. Epidermal growth factor receptor
      expression was present in 41 (80%) cases, with moderate or strong epidermal
      growth factor receptor staining in 30 (59%) cases. HER-2/neu was positive in 2
      (4%) cases. Fluorescence in situ hybridization analysis showed gain in epidermal
      growth factor receptor gene copy number in 17 (46%) tumors. Of the latter, 1
      showed gene amplification, whereas all others showed gain in chromosome 7,
      indicating balanced polysomy. Epidermal growth factor receptor overexpression by
      immunohistochemistry correlated significantly with epidermal growth factor
      receptor copy number by fluorescence in situ hybridization (P = .02). HER2/neu
      expression is uncommon in these tumors.

PMID- 20040391
TI  - Mast cell phenotypes and microvessels in non-small cell lung cancer and its
      prognostic significance.
AB  - The impact of interstitial inflammatory cells, such as mast cells, and
      angiogenesis on the prognosis of cancer patients has been reported in many solid
      tumors, although there is disagreement about their role. We undertook a
      retrospective study with tissue samples from 65 patients with stage I and II non
      small cell lung cancer to assess the clinical pathologic role and prognostic
      significance of mast cells. Mast cell phenotypes were identified by
      immunohistochemistry for tryptase and chymase. In addition, we identified
      microvessels using the endothelial marker CD34. Mast cell and microvessel density
      was quantified by assessing immunopositive cells in the intratumoral and
      peritumoral zones of tumor specimens. Both mast cell and microvessel density was
      higher in the peritumoral zone than the intratumoral zone (P <or= .05). A
      positive correlation between mast cell (tryptase-chymase phenotype) and
      microvessel densities was observed in the intratumoral zone (P <or= .05),
      supporting the involvement of mast cells in the angiogenic process. Regarding
      survival, a subset of stage I patients had a worse prognosis at five years when
      low mast cell (tryptase-chymase phenotype) density was found in the peritumoral
      zone (median survival in months [range]: 27 [1-60] versus 46 [1-60]).
      Multivariate Cox analysis indicated that this parameter may be an independent
      prognostic factor (P <or= .05) useful for selecting candidates for earlier
      treatment.

PMID- 20040393
TI  - Factitial soft tissue pseudotumor due to injection of anabolic steroids: a report
      of 3 cases in 2 patients.
AB  - Traumatically induced inflammation or reactive processes are a relatively well
      known phenomenon in both skin and soft tissue. These include panniculitides, fat
      necrosis, nodular fasciitis, and nonspecific fibrosis. Occasionally, traumatic
      reactions can be associated with factitial injury due to self-induced blunt
      trauma or injection of chemical agents. Factitial pseudotumors of soft tissue
      mimicking neoplasms and occurring in deep-seated locations are rare and not well
      recognized. We have had the opportunity to review a handful of cases over the
      years of soft tissue pseudotumors caused by self injection of steroids for the
      purposes of bodybuilding. Three of these cases in 2 patients are presented here.
      One patient developed a deep lateral thigh mass that was radiologically
      suspicious for sarcoma but upon core biopsy was found to be a lipogranulomatous
      reaction. The second patient had 2 masses occurring in the upper and lower
      extremity with an interval of 1 year between the two. This patient had both
      masses resected. The first had the appearance of a giant cell tumor with no
      immediately discernible foreign material. The second mass was initially presumed
      to be a metastasis from the upper extremity tumor and showed similar areas to the
      first specimen; however, it also had areas of obvious reactive features with
      foreign material. These features were found in the first tumor as well upon
      retrospective review. Both patients admitted to self injection of anabolic
      steroids after further history was sought by the clinicians. Deep soft tissue
      pseudosarcomas caused by injection of steroids are not well documented, and
      patient's reluctance to provide this information leads to difficulty in arriving
      at a correct diagnosis. Recognition of this possibility is important in avoiding
      incorrect diagnoses and unnecessary treatments.

PMID- 20040394
TI  - Enkephalin, its precursor, processing enzymes, and receptor as part of a local
      opioid network throughout the respiratory system of lung cancer patients.
AB  - Evidence is accumulating regarding the local opioid regulation of physiologic
      respiratory functions. However, anatomical evidence for a local opioid network of
      the respiratory system is scarce. In this study, tissue samples from 12 lung
      cancer patients undergoing lobectomy or pneumonectomy were examined
      immunohistochemically for the expression of the opioid network components met
      enkephalin, the respective precursor proenkephalin, the key processing enzymes
      prohormone convertases 1 and 2, carboxypeptidase E, and the delta opioid receptor
      in different areas of human lung. Colocalization of proenkephalin with met
      enkephalin, prohormone convertase 1, prohormone convertase 2, and
      carboxypeptidase E was demonstrated by double-immunofluorescence confocal
      microscopy in alveolar macrophages, submucosal glands, cancerous cells, and
      pulmonary neuroendocrine cells of bronchial epithelium. Corresponding delta
      opioid receptor was identified on cells of all these functionally relevant
      anatomical structures and on substance P-immunoreactive sensory nerve fibers
      arborizing within bronchial epithelium. Our findings provide evidence of a local
      opioid network, that is, the exact anatomical localization of proenkephalin, its
      functionally active peptide met-enkephalin, and the key processing enzymes as
      well as corresponding delta opioid receptor, linked to functionally important
      structures of the respiratory system. These findings encourage future studies to
      examine the functional role of local opioid peptides within the respiratory
      system.

PMID- 20040395
TI  - Fibrocytes are involved in the pathogenesis of human chronic kidney disease.
AB  - The presence of chronic kidney disease in humans is associated with a risk of
      kidney function loss as well as the development of cardiovascular disease.
      Fibrocytes have been shown to contribute to organ fibrosis. In this study, the
      presence of fibrocytes was investigated immunohistochemically in kidney biopsy
      specimens from 100 patients with chronic kidney disease. In addition, 6 patients
      with thin basement membrane disease were studied as a disease control. In
      patients with chronic kidney disease, the infiltration of fibrocytes was observed
      mainly in the interstitium. The number of interstitial fibrocytes in patients
      with chronic kidney disease was higher than that in patients with thin basement
      membrane disease. The number of infiltrated fibrocytes in the interstitium
      correlated well with the severity of tubulointerstitial lesions, such as
      interstitial fibrosis, in patients with chronic kidney disease. In addition,
      there were significant correlations between the number of interstitial fibrocytes
      and the number of CD68-positive macrophages in the interstitium as well as
      urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was
      an inverse correlation between the number of interstitial fibrocytes and kidney
      function at the time of biopsy. Finally, the numbers of interstitial fibrocytes
      and macrophages as well as urinary CCL2 levels were significantly decreased
      during convalescence induced by glucocorticoid therapy. These results suggest
      that fibrocytes may be involved in the pathogenesis of chronic kidney disease
      through the interaction with macrophages as well as CCL2.

PMID- 20040396
TI  - Estimating rainforest biomass stocks and carbon loss from deforestation and
      degradation in Papua New Guinea 1972-2002: Best estimates, uncertainties and
      research needs.
AB  - Reduction of carbon emissions from tropical deforestation and forest degradation
      is being considered a cost-effective way of mitigating the impacts of global
      warming. If such reductions are to be implemented, accurate and repeatable
      measurements of forest cover change and biomass will be required. In Papua New
      Guinea (PNG), which has one of the world's largest remaining areas of tropical
      forest, we used the best available data to estimate rainforest carbon stocks, and
      emissions from deforestation and degradation. We collated all available PNG field
      measurements which could be used to estimate carbon stocks in logged and unlogged
      forest. We extrapolated these plot-level estimates across the forested landscape
      using high-resolution forest mapping. We found the best estimate of forest carbon
      stocks contained in logged and unlogged forest in 2002 to be 4770 Mt (+/-13%).
      Our best estimate of gross forest carbon released through deforestation and
      degradation between 1972 and 2002 was 1178 Mt (+/-18%). By applying a long-term
      forest change model, we estimated that the carbon loss resulting from
      deforestation and degradation in 2001 was 53 Mt (+/-18%), rising from 24 Mt (+/
      15%) in 1972. Forty-one percent of 2001 emissions resulted from logging, rising
      from 21% in 1972. Reducing emissions from logging is therefore a priority for
      PNG. The large uncertainty in our estimates of carbon stocks and fluxes is
      primarily due to the dearth of field measurements in both logged and unlogged
      forest, and the lack of PNG logging damage studies. Research priorities for PNG
      to increase the accuracy of forest carbon stock assessments are the collection of
      field measurements in unlogged forest and more spatially explicit logging damage
      studies.

PMID- 20040397
TI  - Experimental and numerical investigations of vibration characteristics for
      parallel-type and series-type triple-layered piezoceramic bimorphs.
AB  - The dynamic characteristics of parallel-type and series-type piezoelectric
      bimorphs are analyzed in this study. The transverse (out-of-plane) and planar (in
      plane) vibrations for piezoceramic bimorphs in normal and abnormal connections
      are investigated experimentally by 2 noncontact optical techniques and impedance
      analyzer. Electronic speckle pattern interferometry (ESPI) is the major
      experimental technique for measuring the resonant frequency and corresponding
      vibration mode shape. Out-of-plane and in-plane vibrations of piezoelectric
      bimorphs at resonance are obtained by a self-arranged ESPI optical setup. The
      laser Doppler vibrometer (LDV) is a point-wise measurement technique for out-of
      plane displacement and is used to determine the out-of-plane resonant
      frequencies. The impedance analyzer is used to measure the resonant frequencies
      for in-plane motions. It is noted from the experimental results that the out-of
      plane modes are the dominant motion for the normal connection and only symmetric
      vibration mode shapes can be excited. The in-plane motions are large enough to be
      measured using the ESPI method for normal connections. The in-plane resonant
      modes are observed for parallel-type piezoelectric bimorph in parallel
      connections; however, the in-plane mode shapes are similar to the out-of-plane
      mode shapes for the series-type piezoelectric bimorph in series connection.
      Hence, the particle motions of the piezoelectric bimorph at resonance are
      essentially 3-D for the normal connection. It is interesting to note that both
      symmetric and asymmetric out-of-plane vibration mode shapes can be excited with
      large applied voltage but no in-plane motion is observed for the abnormal
      connection. In addition to experimental methods, numerical computations based on
      the finite element method are used to verify the experimental results. Good
      agreements of the resonant frequencies and mode shapes are obtained for
      experimental and numerical results.

PMID- 20040399
TI  - Optimal thresholds of feature tracking for blood velocity and tissue motion
      estimation.
AB  - Feature tracking is an algorithm for estimating blood flow velocity and tissue
      motion using pulse-echo ultrasound. In contrast to cross-correlation speckle
      tracking techniques, feature tracking identifies features at discrete locations
      and corresponds them from frame to frame. Prior studies have demonstrated that
      feature-tracking estimates exhibit lower variance than those obtained by the
      conventional autocorrelation method and require less computational complexity
      than either speckle tracking or autocorrelation. To date, not much attention has
      been paid to the process by which trackable features (normally local maxima) are
      selected from the set of all available features. In the selection process, it is
      desired to minimize flow estimate variance while providing sufficient spatial and
      temporal coverage of flow area. Flow studies were performed with a blood flow
      phantom, 3.5-MHz spherically focused transducer, and a pulser/receiver. Values
      were selected for the amplitude threshold (based on the RMS value) and width
      thresholds (based on the wavelength corresponding to transducer center
      frequency). The performance of this method using different threshold values was
      evaluated by the estimate standard deviation and number of features available to
      track. Results show that an optimal width threshold occurs at about 40 to 45% of
      the transmission wavelength, while a trade-off exists between amplitude
      thresholds and spatial flow field coverage. Both the standard deviation of
      estimated velocities and number of available features decrease with increasing
      threshold (either amplitude or width). This affords a user a method of
      determining optimal feature tracking thresholds depending on the specific flow
      application. Judicious selection of feature thresholds can decrease the estimate
      standard deviation by more than 25%.

PMID- 20040398
TI  - Accelerated focused ultrasound imaging.
AB  - One of the most basic trade-offs in ultrasound imaging involves frame rate,
      depth, and number of lines. Achieving good spatial resolution and coverage
      requires a large number of lines, leading to decreases in frame rate. An even
      more serious imaging challenge occurs with imaging modes involving spatial
      compounding and 3-D/4-D imaging, which are severely limited by the slow speed of
      sound in tissue. The present work can overcome these traditional limitations,
      making ultrasound imaging many-fold faster. By emitting several beams at once,
      and by separating the resulting overlapped signals through spatial and temporal
      processing, spatial resolution and/or coverage can be increased by many-fold
      while leaving frame rates unaffected. The proposed approach can also be extended
      to imaging strategies that do not involve transmit beamforming, such as synthetic
      aperture imaging. Simulated and experimental results are presented where imaging
      speed is improved by up to 32-fold, with little impact on image quality. Object
      complexity has little impact on the method's performance, and data from
      biological systems can readily be handled. The present work may open the door to
      novel multiplexed and/or multidimensional protocols considered impractical today.

PMID- 20040400
TI  - Reconstructive compounding for IVUS palpography.
AB  - This study proposes a novel algorithm for luminal strain reconstruction from
      sparse irregularly sampled strain measurements. It is based on the normalized
      convolution (NC) algorithm. The novel extension comprises the multilevel scheme,
      which takes into account the variable sampling density of the available strain
      measurements during the cardiac cycle. The proposed algorithm was applied to
      restore luminal strain values in intravascular ultrasound (IVUS) palpography. The
      procedure of reconstructing and averaging the strain values acquired during one
      cardiac cycle forms a technique, coined as reconstructive compounding. The
      accuracy of strain reconstruction was initially tested on the luminal strain map,
      computed from 3 in vivo IVUS pullbacks. The high quality of strain restoration
      was observed after systematically removing up to 90% of the initial elastographic
      measurements. The restored distributions accurately reproduced the original
      strain patterns and the error did not exceed 5%. The experimental validation of
      the reconstructed compounding technique was performed on 8 in vivo IVUS
      pullbacks. It demonstrated that the relative decrease in number of invalid strain
      estimates amounts to 92.05 +/- 6.03% and 99.17 +/- 0.92% for the traditional and
      reconstructive strain compounding schemes, respectively. In conclusion,
      implementation of the reconstructive compounding scheme boosts the diagnostic
      value of IVUS palpography.

PMID- 20040402
TI  - Autonomous corrosion detection in gas pipelines: a hybrid-fuzzy classifier
      approach using ultrasonic nondestructive evaluation protocols.
AB  - In this paper, a customized classifier is presented for the industry-practiced
      nondestructive evaluation (NDE) protocols using a hybrid-fuzzy inference system
      (FIS) to classify the corrosion and distinguish it from the geometric defects or
      normal/healthy state of the steel pipes used in the gas/petroleum industry. The
      presented system is hybrid in the sense that it utilizes both soft computing
      through fuzzy set theory, as well as conventional parametric modeling through
      H(infinity) optimization methods. Due to significant uncertainty in the power
      spectral density of the noise in ultrasonic NDE procedures, the use of optimal
      H(2) estimators for defect characterization is not so accurate. A more
      appropriate criterion is the H(infinity) norm of the estimation error spectrum
      which is based on minimization of the magnitude of this spectrum and hence
      produces more robust estimates. A hybrid feature set is developed in this work
      that corresponds to a) geometric features extracted directly from the raw
      ultrasonic A-scan data (which are the ultrasonic echo pulses in 1-Dtraveling
      inside the metal perpendicular to its 2 surfaces) and b) mapped features from the
      impulse response of the estimated model of the defect waveform under study. An
      experimental strategy is first outlined, through which the necessary data are
      collected as A-scans. Then, using the H(infinity) estimation approach, a
      parametric transfer function is obtained for each pulse. In this respect, each A
      scan is treated as output from a defining function when a pure/healthy metal's A
      scan is used as its input. Three defining states are considered in the paper;
      healthy, corroded, and defective, where the defective class represents metal with
      artificial or other defects. The necessary features are then calculated and are
      then supplied to the fuzzy inference system as input to be used in the
      classification. The resulting system has shown excellent corrosion classification
      with very low misclassification and false alarm rates.

PMID- 20040401
TI  - Functional changes in arteries induced by pulsed high-intensity focused
      ultrasound.
AB  - Continuous high-intensity focused ultrasound (HIFU) at various intensities has
      been shown to induce functional changes in arteries. The objective of the current
      study was to investigate the functional changes in arteries when pulsed HIFU is
      used at various acoustic power levels. Sonication was applied at an ultrasound
      frequency of 1 MHz with a burst length of 50 ms and a repetition frequency of 1
      Hz. The duration of the whole sonication was 6 s. The femoral arteries and
      abdominal aortas of Sprague-Dawley rats were surgically exposed and sonicated
      with pulsed HIFU; the pulsed-HIFU beam was aimed using color images of the blood
      flow. The peak systolic velocity (PSV) of the blood flow, as measured by Doppler
      velocimetry, increased in the arteries to which pulsed HIFU had been applied at
      acoustic powers of 15, 30, and 45 W. The increase in PSV was correlated with the
      acoustic power of the pulsed HIFU. The temperatures recorded by the thermocouples
      placed above and below the aorta surfaces did not change significantly during the
      sonication. Furthermore, no histological changes were found and the vessel wall
      showed no obvious temperature rise. Therefore, our results indicate that the
      functional changes induced by pulsed-HIFU exposure are mainly due to mechanical
      effects.

PMID- 20040403
TI  - Evaluation of the damage detection capability of a sparse-array guided-wave SHM
      system applied to a complex structure under varying thermal conditions.
AB  - A sparse-array structural health monitoring (SHM) system based on guided waves
      was applied to the door of a commercial shipping container. The door comprised a
      corrugated steel panel approximately 2.4 m by 2.4 m surrounded by a box beam
      frame and testing was performed in a nonlaboratory environment. A 3-D finite
      element (FE) model of the corrugations was used to predict transmission
      coefficients for the A0 and S0 modes across the corrugations as a function of
      incidence angle. The S0 mode transmission across the corrugations was
      substantially stronger, and this mode was used in the main test series. A sparse
      array with 9 transducers was attached to the structure, and signals from the
      undamaged structure were recorded at periodic intervals over a 3-week period, and
      the resulting signal database was used for temperature compensation of subsequent
      signals. Defects in the form of holes whose diameter was increased incrementally
      from 1 to 10 mm were introduced at 2 different points of the structure, and
      signals were taken for each condition. Direct analysis of subtracted signals
      allowed understanding of the defect detection capability of the system.
      Comparison of signals transmitted between different transducer pairs before and
      after damage was used to give an initial indication of defect detectability.
      Signals from all combinations of transducers were then used in imaging
      algorithms, and good localization of holes with a 5-mm diameter or above was
      possible within the sparse array, which covered half of the area of the
      structure.

PMID- 20040404
TI  - Modeling and experimental study on near-field acoustic levitation by flexural
      mode.
AB  - Near-field acoustic levitation (NFAL) has been used in noncontact handling and
      transportation of small objects to avoid contamination. We have performed a
      theoretical analysis based on nonuniform vibrating surface to quantify the
      levitation force produced by the air film and also conducted experimental tests
      to verify our model. Modal analysis was performed using ANSYS on the flexural
      plate radiator to obtain its natural frequency of desired mode, which is used to
      design the measurement system. Then, the levitation force was calculated as a
      function of levitation distance based on squeeze gas film theory using measured
      amplitude and phase distributions on the vibrator surface. Compared with previous
      fluid-structural analyses using a uniform piston motion, our model based on the
      nonuniform radiating surface of the vibrator is more realistic and fits better
      with experimentally measured levitation force.

PMID- 20040405
TI  - Thermal behavior of BAW filters at high RF power levels.
AB  - The temperature increase of bulk acoustic wave filters at high RF power levels
      has been investigated. Self-heating due to power dissipation in the filter leads
      to a nonuniform frequency shift of the insertion loss. At the right filter skirt,
      self-heating is amplified by the negative temperature coefficient of frequency.
      We demonstrate that at high RF power levels, this can cause thermal instabilities
      resulting in an abrupt step in the insertion loss. A novel frequency
      transformation is introduced to describe the nonuniform frequency shift of the
      insertion loss as well as the thermal instabilities. A condition for the
      occurrence of thermal instabilities is derived. It is argued that because of this
      nonuniform frequency shift at high power levels, accelerated lifetime tests can
      overestimate the lifetime, if the stress frequency is not compensated for self
      heating. Here, the frequency transformation is used to determine the stress
      frequencies at high RF power levels from low-power S-parameter measurements.

PMID- 20040406
TI  - An exact analysis of surface acoustic waves in a plate of functionally graded
      materials.
AB  - Some traditional applications of structures and devices with homogeneous
      materials are being gradually replaced by functionally graded materials (FGM)
      with spatial variation of properties. The analysis of SAW propagating in FGM
      structures will be different primarily due to variations of material properties
      and resulting differential equations with variable coefficients. To provide an
      effective method and accurate results for the analysis of SAWs in FGM structures,
      we employed the Frobenius method as the only available method for a detailed
      analysis of SAW in materials with property variations in a linear pattern.
      Analytical examples are presented to demonstrate the effectiveness of the method
      and the effect of FGM on changes of surface displacements in SAW propagation.

PMID- 20040407
TI  - Micromachined thin film plate acoustic wave resonators (FPAR): Part II.
AB  - Improved performance thin-film plate acoustic wave resonators (FPAR) using the
      lowest order symmetric Lamb wave (S0) propagating in highly textured AlN
      membranes have been previously demonstrated for the first time. In this work, an
      experimental study of the resonators' performance vs. a variety of design
      parameters is performed. Devices operating in the vicinity of the stopband center
      exhibiting a Q-value of up to 3000 at a frequency of around 875 MHz are
      demonstrated. Further, low-loss high-Q micromachined 2-port longitudinally
      coupled thin-film resonators using the S0 mode are demonstrated for the first
      time. For the analysis of the proposed structures, the coupling-of-modes (COM)
      approach is successfully employed. Initially, the COM model is used for the
      extraction of physical parameters from one-port FPAR measurements. Subsequently,
      using the COM model, a satisfactory agreement with the proposed experimental
      frequency characteristics of S0 2-port FPARs has been achieved, and possibilities
      for further improvements in the performance discussed. Finally, the frequency
      spectrum of the one-port devices has been studied and the excited plate modes at
      different frequencies identified and presented with their Q-factors and
      temperature coefficients of frequency (TCF).

PMID- 20040408
TI  - CMUT characterization by interferometric and electric measurements.
AB  - Capacitive micromachined ultrasonic transducers (CMUTs) with 5.7 mum radius,
      realized by wafer bonding, have been characterized by both optical and electrical
      measurements. These measurements are performed by our heterodyne interferometer
      and a network analyzer, respectively. The results from this article will be used
      to improve the fabrication of next-generation CMUTs. We have investigated the
      spread in resonance frequency of different CMUT membranes along the array. Q
      factors have been obtained using both measurement methods, and the results from
      the 2 methods have been numerically compared. The relation between applied dc
      voltage and resonance frequency has been studied. Temperature measurements show
      that increasing temperature leads to a small decrease in the resonance frequency
      of the CMUTs; however, the decrease is small enough to ensure stable operation
      with small variations in room temperature. The heterodyne interferometer is used
      to inspect the vibration pattern of the CMUTs' higher harmonic modes. These modes
      are located at approximately 60 MHz in air. To the authors' knowledge, vibration
      modes at frequencies >40 MHz have not been previously studied.

PMID- 20040409
TI  - Design and experimental study of microcantilever ultrasonic detection
      transducers.
AB  - This paper presents the analysis, design, and experimental study of a
      microcantilever optically-activated ultrasonic detection transducer. An
      analytical model was derived using 1-D cantilever structural dynamics, leading to
      the optimization of the transducer design. Finite element modeling enabled
      dynamic simulation to be performed, with results in good agreement with the
      analytical model. Transducers were fabricated using MEMS (microelectromechanical
      systems) techniques. Experimental results are presented on remote noncontact
      detection of ultrasound using the fabricated transducers; high SNR is achieved
      for the detected signals, even for relatively low ultrasonic amplitudes. Both
      analysis and experimental study show that the transducer has a sensitivity
      approximately 1 to 2 orders of magnitude higher than that of conventional optical
      detection techniques. Furthermore, we show that the dominant factor in the
      increased sensitivity of the transducer is the resonant nature of the finger
      structure.

PMID- 20040410
TI  - Exploitation of capacitive micromachined transducers for nonlinear ultrasound
      imaging.
AB  - Capacitive micromachined ultrasonic transducers (CMUTs) present advantages such
      as wide frequency bandwidth, which could be further developed for nonlinear
      imaging. However, the driving electrostatic force induces a nonlinear behavior of
      the CMUT, thus generating undesirable harmonic components in the generated
      acoustic signal. Consequently, the use of CMUT for harmonic imaging (with or
      without contrast agents) becomes challenging. This paper suggests 2 compensation
      approaches, linear and nonlinear methods, to cancel unwanted nonlinear
      components. Furthermore, nonlinear responses from contrast agent were evaluated
      using CMUT in transmit before and after compensation. The results were compared
      with those obtained using a PZT transducer in transmit. Results showed that CMUT
      nonlinear behavior is highly influenced by the excitation to bias voltage ratio.
      Measurements of output pressure very close to the CMUT surface allow the
      estimation of optimal parameters for each compensation approach. Both methods
      showed a harmonic reduction higher than 20 dB when one element or several
      elements are excited. In addition, the study demonstrates that nonlinear approach
      seems to be more efficient because it is shown to be less sensitive to
      interelement variability and further avoids fundamental component deterioration.
      The results from contrast agent measurements showed that the responses obtained
      using CMUT elements in transmit with compensation were similar to those from PZT
      transducer excitation. This experimental study demonstrates the opportunity to
      use CMUT with traditional harmonic contrast imaging techniques.

PMID- 20040411
TI  - Bilayer piezoelectric/electrostrictive (P/E) dome unimorph.
AB  - We present a new type of actuator named bilayer piezoelectric/electrostrictive
      dome unimorph (BIPEDU), fabricated by attaching a piezoelectric-electrostrictive
      monolithic bilayer composites (PE-MBLC) to a metal plate. Various ratios of
      piezoelectric/electrostrictive (P/E) volume percent were used to form PE-MBLC. It
      was found that d(33)(eff) and K(eff) in PE-MBLC follow the series 2-2 composite
      mixing rule. However, the measured results were slightly lower than those of the
      calculated values because of a large difference in dielectric displacement
      between piezoelectric and electrostrictive layers and because the electrostrictor
      acts as the resistor that impedes the domain switching in piezoelectric layer
      during poling. In addition, we have investigated the field-induced displacement
      in PE-MBLC and BIPEDU actuators. In comparison, the displacement of BIPEDU
      actuators was much higher than that of PE-MBLC actuators. This was attributed to
      the good quality of bonding between ceramic and metal, which contributed to the
      proper stress/force transfer, as well as the metal sheet, which acted as a
      flextentional structure for PE-MBLC to generate more axial displacement in BIPEDU
      actuators. The load dependence of displacement in BIPEDU was obtained. In
      addition, the BIPEDU showed high reliability during the displacement cyclic
      testing.

PMID- 20040412
TI  - Theoretical modeling of frequency-dependent magnetoelectric effects in laminated
      multiferroic plates.
AB  - The recently derived 2-D equations for extensional, flexural, and thickness-shear
      motions of laminated plates of piezoelectric/piezomagnetic layers are employed in
      the analysis of the frequency dependence of magnetoelectric couplings in
      laminated plates of piezoelectric and piezomagnetic layers driven by time
      harmonic magnetic fields. Four structures are analyzed. Two are symmetric about
      the middle plane and are for extensional motions. The other 2 are antisymmetric
      about the middle plane and are for flexural motions. Frequency-dependent
      magnetoelectric effects are calculated and compared. Near resonances, the time
      dependent magnetoelectric coupling coefficients are found to be much larger than
      the static magnetoelectric coupling coefficients.

PMID- 20040413
TI  - Design and fabrication of PIN-PMN-PT single-crystal high-frequency ultrasound
      transducers.
AB  - High-frequency PIN-PMN-PT single crystal ultrasound transducers at center
      frequencies of 35 MHz and 60 MHz were successfully fabricated using lead indium
      niobate-lead magnesium niobate-lead titanate (0.23PIN- 0.5PMN-0.27PT) single
      crystal. The new PIN-PMN-PT single crystal has higher coercivity (6.0 kV/cm) and
      higher Curie temperature (160 degrees C) than PMN-PT crystal. Experimental
      results showed that the PIN-PMN-PT transducers have similar performance but
      better thermal stability compared with the PMN-PT transducers.

PMID- 20040414
TI  - A simple approximate formula for the physical focal length of spherically focused
      transducers.
AB  - A simple approximate formula is presented to describe the relationship between
      the physical focal lengths and the geometric focal lengths of spherically focused
      transducers with ultrasonic fields. This simple expression applies regardless of
      whether the focus strength is strong or weak, and regardless of whether the
      fluids are non-attenuating or attenuating. Analysis results show that the average
      error of the simple approximate formula is certainly less than 2% relative to the
      numerical solution.

PMID- 20040415
TI  - Recursive Bayesian recurrent neural networks for time-series modeling.
AB  - This paper develops a probabilistic approach to recursive second-order training
      of recurrent neural networks (RNNs) for improved time-series modeling. A general
      recursive Bayesian Levenberg-Marquardt algorithm is derived to sequentially
      update the weights and the covariance (Hessian) matrix. The main strengths of the
      approach are a principled handling of the regularization hyperparameters that
      leads to better generalization, and stable numerical performance. The framework
      involves the adaptation of a noise hyperparameter and local weight prior
      hyperparameters, which represent the noise in the data and the uncertainties in
      the model parameters. Experimental investigations using artificial and real-world
      data sets show that RNNs equipped with the proposed approach outperform standard
      real-time recurrent learning and extended Kalman training algorithms for
      recurrent networks, as well as other contemporary nonlinear neural models, on
      time-series modeling.

PMID- 20040416
TI  - Two-dimensional imaging via a narrowband MIMO radar system with two perpendicular
      linear arrays.
AB  - This paper presents a system model and method for the 2-D imaging application via
      a narrowband multiple-input multiple-output (MIMO) radar system with two
      perpendicular linear arrays. Furthermore, the imaging formulation for our method
      is developed through a Fourier integral processing, and the parameters of antenna
      array including the cross-range resolution, required size, and sampling interval
      are also examined. Different from the spatial sequential procedure sampling the
      scattered echoes during multiple snapshot illuminations in inverse synthetic
      aperture radar (ISAR) imaging, the proposed method utilizes a spatial parallel
      procedure to sample the scattered echoes during a single snapshot illumination.
      Consequently, the complex motion compensation in ISAR imaging can be avoided.
      Moreover, in our array configuration, multiple narrowband spectrum-shared
      waveforms coded with orthogonal polyphase sequences are employed. The mainlobes
      of the compressed echoes from the different filter band could be located in the
      same range bin, and thus, the range alignment in classical ISAR imaging is not
      necessary. Numerical simulations based on synthetic data are provided for testing
      our proposed method.

PMID- 20040417
TI  - Rate-distortion optimized bitstream extractor for motion scalability in wavelet
      based scalable video coding.
AB  - Motion scalability is designed to improve the coding efficiency of a scalable
      video coding framework, especially in the medium to low range of decoding bit
      rates and spatial resolutions. In order to fully benefit from the superiority of
      motion scalability, a rate-distortion optimized bitstream extractor, which
      determines the optimal motion quality layer for any specific decoding scenario,
      is required. In this paper, the determination process first starts off with a
      brute force searching algorithm. Although guaranteed by the optimal performance
      within the search domain, it suffers from high computational complexities. Two
      properties, i.e., the monotonically nondecreasing property and the unimodal
      property, are then derived to accurately describe the rate-distortion behavior of
      motion scalability. Based on these two properties, modified searching algorithms
      are proposed to reduce the complexity (up to five times faster) and to achieve
      the global optimality, even for those decoding scenarios outside the search
      domain.

PMID- 20040418
TI  - Object recognition through topo-geometric shape models using error-tolerant
      subgraph isomorphisms.
AB  - We propose a method for 3-D shape recognition based on inexact subgraph
      isomorphisms, by extracting topological and geometric properties of a shape in
      the form of a shape model, referred to as topo-geometric shape model (TGSM). In a
      nutshell, TGSM captures topological information through a rigid transformation
      invariant skeletal graph that is constructed in a Morse theoretic framework with
      distance function as the Morse function. Geometric information is then retained
      by analyzing the geometric profile as viewed through the distance function.
      Modeling the geometric profile through elastic yields a weighted skeletal
      representation, which leads to a complete shape signature. Shape recognition is
      carried out through inexact subgraph isomorphisms by determining a sequence of
      graph edit operations on model graphs to establish subgraph isomorphisms with a
      test graph. Test graph is recognized as a shape that yields the largest subgraph
      isomorphism with minimal cost of edit operations. In this paper, we propose
      various cost assignments for graph edit operations for error correction that
      takes into account any shape variations arising from noise and measurement
      errors.

PMID- 20040419
TI  - Registering a multisensor ensemble of images.
AB  - Many registration scenarios involve aligning more than just two images. These
      image sets-called ensembles-are conventionally registered by choosing one image
      as a template, and every other image is registered to it. This pairwise approach
      is problematic because results depend on which image is chosen as the template.
      The issue is particularly acute for multisensor ensembles because different
      sensors create images with different features. Also, pairwise methods use only a
      fraction of the available data at a time. In this paper, we propose a maximum
      likelihood clustering method that registers all the images in a multisensor
      ensemble simultaneously. Experiments involving rigid-body and affine
      transformations show that the clustering method is more robust and accurate than
      competing pairwise registration methods. Moreover, the clustering results can be
      used to form a rudimentary segmentation of the image ensemble.

PMID- 20040420
TI  - Poisson's ratios of auxetic and other technological materials.
AB  - Poisson's ratio, the relation between lateral contraction of a thin, linearly
      elastic rod when subjected to a longitudinal extension, has a long and
      interesting history. For isotropic bodies, it can theoretically range from +1/2
      to -1; the experimental gamut for anisotropics is even larger. The ratio is
      positive for all combinations of directions in most crystals. But as far back as
      the 1800s, Voigt and others found that negative values were encountered for some
      materials, a property now called auxeticity. Here we examine this property from
      the point of view of crystal stability and compute extrema of the ratio for
      various interesting and technologically important materials. Potential
      applications of the auxetic property are mentioned.

PMID- 20040421
TI  - Change in piezoelectric boundary acoustic wave characteristics with overlay and
      metal grating materials.
AB  - This paper describes how the characteristics of shear-horizontal type
      piezoelectric boundary acoustic waves (PBAWs) change with combination of
      different overlay and metal grating materials. It is shown that PBAWs are
      supported in various structures provided that highly piezoelectric material(s)
      are employed as structural member(s). For verification, numerical simulation of
      different material combinations is done. The results are in good agreement with
      the qualitative prediction. That is, large electromechanical coupling factor K(2)
      is obtainable when materials having small mass densities shear modulus c(44) and
      shear velocity VBS; and materials having extremely large shear modulus c(44) are
      chosen, respectively, for overlay and metallic grating. When YX-LiNbO(3) is
      assumed as a substrate, for example, the best choice seems to be SiO(2) and Au
      for overlay and metallic grating, respectively. Although metals with extremely
      large rho and c(44) such as W and Ta offer large K(2), they may not be acceptable
      for practical PBAW applications because of their large electric resistivity.

PMID- 20040422
TI  - Sputtered SiO2 as low acoustic impedance material for Bragg mirror fabrication in
      BAW resonators.
AB  - In this paper we describe the procedure to sputter low acoustic impedance SiO(2)
      films to be used as a low acoustic impedance layer in Bragg mirrors for BAW
      resonators. The composition and structure of the material are assessed through
      infrared absorption spectroscopy. The acoustic properties of the films (mass
      density and sound velocity) are assessed through X-ray reflectometry and
      picosecond acoustic spectroscopy. A second measurement of the sound velocity is
      achieved through the analysis of the longitudinal lambda/2 resonance that appears
      in these silicon oxide films when used as uppermost layer of an acoustic
      reflector placed under an AlN-based resonator.

PMID- 20040423
TI  - A SAW resonator with two-dimensional reflectors.
AB  - It is known that a part of the loss of leaky SAW resonators is due to radiation
      of acoustic energy in the bus-bars. Many researchers are working on so-called
      phononic crystals. A 2-D grating of very strong reflectors allows these devices
      to fully reflect, for a given frequency band, any incoming wave. A new device
      based on the superposition of a regular SAW resonator and a 2-D periodic grating
      of reflectors is proposed. Several arrangements and geometries of the reflectors
      were studied and compared experimentally on 48 degrees rotated Y-cut lithium
      tantalate. In particular, a very narrow aperture (7.5 lambda) resonator was
      manufactured in the 900 MHz range. Because of its small size, this resonator has
      a resonance Q of only 575 when using the standard technology, whereas a resonance
      Q of 1100 was obtained for the new device without degradation of the other
      characteristics. Because of the narrow aperture, the admittance of the standard
      resonator showed a very strong parasitic above the resonance frequency, whereas
      this effect is drastically reduced for the new device. These results demonstrate
      the feasibility of the new approach.

PMID- 20040424
TI  - Super-high-frequency two-port AlN contour-mode resonators for RF applications.
AB  - This paper reports on the design and experimental verification of a new class of
      thin-film (250 nm) superhigh- frequency laterally-vibrating piezoelectric
      microelectromechanical (MEMS) resonators suitable for the fabrication of narrow
      band MEMS filters operating at frequencies above 3 GHz. The device dimensions
      have been opportunely scaled both in the lateral and vertical dimensions to
      excite a contour-extensional mode of vibration in nanofeatures of an ultra-thin
      (250 nm) AlN film. In this first demonstration, 2-port resonators vibrating up to
      4.5 GHz have been fabricated on the same die and attained electromechanical
      coupling, kt(2), in excess of 1.5%. These devices are employed to synthesize the
      highest frequency MEMS filter (3.7 GHz) based on AlN contour-mode resonator
      technology ever reported.

PMID- 20040425
TI  - Theoretical analysis of SAW propagation characteristics in (100) oriented
      AlN/diamond structure.
AB  - In this study, the finite element method is employed to calculate SAW
      characteristics in (100) AlN/diamond based structures with different electrical
      interfaces; i.e., IDT/ AlN/diamond, AlN/IDT/diamond, IDT/AlN/thin metal film/
      diamond, and thin metal film/AlN/IDT/diamond. The effects of Cu and Al electrodes
      as well as the thickness of electrode on phase velocity, coupling coefficient,
      and reflectivity of SAWs are illustrated. Propagation characteristics of SAWs in
      (002) AlN/diamond-based structures are also presented for comparison. Simulation
      results show that to retain a large reflectivity for the design of RF filters and
      duplexers, the Cu IDT/(100) AlN/diamond structure possesses the highest phase
      velocity and largest coupling coefficient at the smallest AlN film thickness- to
      wavelength ratio.

PMID- 20040426
TI  - Bulk acoustic wave filters synthesis and optimization for multi-standard
      communication terminals.
AB  - This article presents a design methodology for bulk acoustic wave (BAW) filters.
      First, an overview of BAW physical principles, BAW filter synthesis, and the
      modified Butterworth-van Dyke model are addressed. Next, design and optimization
      methodology is presented and applied to a mixed ladder-lattice BAW bandpass
      filter for the Universal Mobile Telecommunications System (UMTS) TX-band at 1.95
      GHz and to ladder and lattice BAW bandpass filters for the DCS1800 TX-band at
      1.75 GHz. In each case, BAW filters are based on AlN resonators. UMTS filter is
      designed with conventional molybdenum electrodes whereas DCS filters electrodes
      are made with innovative iridium.

PMID- 20040427
TI  - High-temperature langatate elastic constants and experimental validation up to
      900 degrees C.
AB  - This paper reports on a set of langatate (LGT) elastic constants extracted from
      room temperature to 1100 degrees C using resonant ultrasound spectroscopy
      techniques and an accompanying assessment of these constants at high temperature.
      The evaluation of the constants employed SAW device measurements from room
      temperature to 900 degrees C along 6 different LGT wafer orientations. Langatate
      parallelepipeds and wafers were aligned, cut, ground, and polished, and acoustic
      wave devices were fabricated at the University of Maine facilities along specific
      orientations for elastic constant extraction and validation. SAW delay lines were
      fabricated on LGT wafers prepared at the University of Maine using 100-nm
      platinumrhodium- zirconia electrodes capable of withstanding temperatures up to
      1000 degrees C. The numerical predictions based on the resonant ultrasound
      spectroscopy high-temperature constants were compared with SAW phase velocity,
      fractional frequency variation, and temperature coefficients of delay extracted
      from SAW delay line frequency response measurements. In particular, the
      difference between measured and predicted fractional frequency variation is less
      than 2% over the 25 degrees C to 900 degrees C temperature range and within the
      calculated and measured discrepancies. Multiple temperature-compensated
      orientations at high temperature were predicted and verified in this paper: 4 of
      the measured orientations had turnover temperatures (temperature coefficient of
      delay = 0) between 200 and 420 degrees C, and 2 had turnover temperatures below
      100 degrees C. In summary, this work reports on extracted high-temperature
      elastic constants for LGT up to 1100 degrees C, confirmed the validity of those
      constants by high-temperature SAW device measurements up to 900 degrees C, and
      predicted and identified temperature-compensated LGT orientations at high
      temperature.

PMID- 20040428
TI  - High-Q X-band distributed Bragg resonator utilizing an aperiodic alumina plate
      arrangement.
AB  - This paper describes a high-Q X-band distributed Bragg resonator that uses an
      aperiodic arrangement of non-lambda/4 low loss alumina plates mounted in a
      cylindrical waveguide. An ABCD parameter waveguide model was developed to
      simulate and optimize the cavity. The dielectric plates and air waveguide
      dimensions were optimized to achieve maximum quality factor by redistributing the
      energy loss within the cavity. An unloaded quality factor (Q(0)) of 196,000 was
      demonstrated at 9.93 GHz.

PMID- 20040429
TI  - The profound impact of negative power law noise on statistical estimation.
AB  - This paper investigates the profound impact of negative power law (neg-p) noise -
      that is, noise with a power spectral density L(p)(f) proportional variant | f
      |(p) for p < 0 - on the ability of practical implementations of statistical
      estimation or fitting techniques, such as a least squares fit (LSQF) or a Kalman
      filter, to generate valid results. It demonstrates that such negp noise behaves
      more like systematic error than conventional noise, because neg-p noise is highly
      correlated, non-stationary, non-mean ergodic, and has an infinite correlation
      time tau(c). It is further demonstrated that stationary but correlated noise will
      also cause invalid estimation behavior when the condition T >> tau(c) is not met,
      where T is the data collection interval for estimation. Thus, it is shown that
      neg-p noise, with its infinite Tau(c), can generate anomalous estimation results
      for all values of T, except in certain circumstances. A covariant theory is
      developed explaining much of this anomalous estimation behavior. However,
      simulations of the estimation behavior of neg-p noise demonstrate that the
      subject cannot be fully understood in terms of covariant theory or mean
      ergodicity. It is finally conjectured that one must investigate the variance
      ergodicity properties of neg-p noise through the use of 4th order correlation
      theory to fully explain such simulated behavior.

PMID- 20040430
TI  - 1.05-GHz CMOS oscillator based on lateral- field-excited piezoelectric AlN
      contour- mode MEMS resonators.
AB  - This paper reports on the first demonstration of a 1.05-GHz
      microelectromechanical (MEMS) oscillator based on lateral-field-excited (LFE)
      piezoelectric AlN contourmode resonators. The oscillator shows a phase noise
      level of -81 dBc/Hz at 1-kHz offset frequency and a phase noise floor of -146
      dBc/Hz, which satisfies the global system for mobile communications (GSM)
      requirements for ultra-high frequency (UHF) local oscillators (LO). The circuit
      was fabricated in the AMI semiconductor (AMIS) 0.5-microm complementary
      metaloxide- semiconductor (CMOS) process, with the oscillator core consuming only
      3.5 mW DC power. The device overall performance has the best figure-of-merit
      (FoM) when compared with other gigahertz oscillators that are based on film bulk
      acoustic resonator (FBAR), surface acoustic wave (SAW), and CMOS on-chip inductor
      and capacitor (CMOS LC) technologies. A simple 2-mask process was used to
      fabricate the LFE AlN resonators operating between 843 MHz and 1.64 GHz with
      simultaneously high Q (up to 2,200) and kt 2 (up to 1.2%). This process further
      relaxes manufacturing tolerances and improves yield. All these advantages make
      these devices suitable for post-CMOS integrated on-chip direct gigahertz
      frequency synthesis in reconfigurable multiband wireless communications.

PMID- 20040431
TI  - Low-phase-noise frequency synthesizer for the trapped atom clock on a chip.
AB  - We report on the realization of a 6.834-GHz synthesis chain for the trapped atom
      clock on a chip (TACC) that is being developed at LNE-SYRTE. The chain is based
      on the frequency multiplication of a 100-MHz reference signal to obtain a signal
      at 6.4 GHz. It uses a comb generator based on a monolithic GaAs nonlinear
      transmission line. This is a novelty in the fabrication of high-stability
      microwave synthesizers. Measurements give a low flicker phase noise of -85
      dBrad(2)/Hz at 1-Hz offset frequency and a white phase noise floor < -115
      dBrad(2)/Hz. Based on these results, we estimate that the performance of the
      synthesizer is at least one order of magnitude better than the stability goal of
      TACC. This ensures that the synthesizer will not be limiting the clock
      performance.

PMID- 20040432
TI  - Black-body radiation shifts and theoretical contributions to atomic clock
      research.
AB  - A review of theoretical calculations of black-body radiation (BBR) shifts in
      various systems of interest to atomic clock research is presented. Calculations
      for monovalent systems, such as Ca(+), Sr(+), and Rb are carried out using a
      relativistic all-order single-double method, where all single and double
      excitations of the Dirac-Fock wave function are included to all orders of
      perturbation theory. A recently developed method for accurate calculations of BBR
      shifts in divalent atoms such as Sr is discussed. This approach combines the
      relativistic allorder method and the configuration interaction method. The
      evaluation of uncertainties in theoretical values of BBR shifts is discussed in
      detail.

PMID- 20040433
TI  - Preliminary results of the trapped atom clock on a chip.
AB  - We present an atomic clock based on the interrogation of magnetically trapped
      (87)Rb atoms. Two photons, in the microwave and radiofrequency domain, excite the
      clock transition. At a magnetic field of 3.23 G the clock transition from |F = 1,
      m(F) = -1> to |F = 2, m(F) = 1> is 1st-order insensitive to magnetic field
      variations. Ramsey interrogation times longer than 2 s can be achieved, leading
      to a projected clock stability in the low 10(-13) at 1 s for a cloud of 10(5)
      atoms. We use an atom chip to cool and trap the atoms. A coplanar waveguide is
      integrated to the chip to carry the Ramsey interrogation signal, making the
      physics package as small as (5 cm)(3). We describe the experimental setup and
      show preliminary Ramsey fringes of line width 1.25 Hz.

PMID- 20040434
TI  - Miniaturized sensors for the viscosity and density of liquids--performance and
      issues.
AB  - This paper reviews our recent work on vibrating sensors for the physical
      properties of fluids, particularly viscosity and density. Several device designs
      and the associated properties, specifically with respect to the sensed
      rheological domain and the onset of non-Newtonian behavior, are discussed.

PMID- 20040435
TI  - Thermal control of a dual mode parametric sapphire transducer.
AB  - We propose a method to control the thermal stability of a sapphire dielectric
      transducer made with 2 dielectric disks separated by a thin gap and resonating in
      the whispering gallery (WG) modes of the electromagnetic field. The simultaneous
      measurement of the frequencies of both a WGH mode and a WGE mode allows one to
      discriminate the frequency shifts due to gap variations from those due to
      temperature instability. A simple model, valid in quasi-equilibrium conditions,
      describes the frequency shift of the 2 modes in terms of 4 tuning parameters. A
      procedure for their direct measurement is presented.

PMID- 20040436
TI  - On-line surveillance of lubricants in bearings by means of surface acoustic
      waves.
AB  - The acoustic wave propagation in bearings filled with lubricants and driven by
      pulsed excitation of surface acoustic waves has been investigated with respect to
      the presence and the distribution of different lubricants. Experimental setups,
      which are based on the mode conversion between surface acoustic waves and
      compression waves at the interface between a solid substrate of the bearing and a
      lubricant are described. The results of preliminary measurements at linear
      friction bearings, rotation ball bearings and axial cylinder roller bearings are
      presented.

PMID- 20040437
TI  - Diffraction in the reflective SAW tags.
AB  - A specific feature of the acoustoelectric scattering of the nonuniform surface
      acoustic wave (SAW) beams by the straight metal strips placed on the
      piezoelectric substrates is discussed. A closed-form solution is obtained to
      describe the influence of diffraction on the reflective delay line with finite
      aperture. The found results allow us to develop the fast simulation and synthesis
      tool that can be applied to evaluate and compensate for the diffraction effect in
      SAW tags of arbitrary architectures. Efficiency of the proposed approach is
      illustrated by example of SAW tag synthesized on 128 degrees -LiNbO(3).

PMID- 20040438
TI  - Algorithms for international atomic time.
AB  - This article reviews the creation and technical evolution of atomic time scales.
      In particular, we focus our attention on the method of calculation and the
      characteristics of International Atomic Time (TAI), and show how it is
      disseminated at the ultimate level of precision.

PMID- 20040439
TI  - The impact of navigation satellite ephemeris error on common-view time transfer.
AB  - The impact of navigation satellite ephemeris error on satellite common-view time
      transfer was analyzed. The impact varies depending on the angle in view of a
      satellite relative to a user (elevation) and the baseline distance between 2
      users. Some extents of the impact were figured out for several elevations and
      different baseline. As an example, results from several common-view time transfer
      links in China via Compass satellite were given.

PMID- 20040440
TI  - Studies and possible improvements on the EAL algorithm.
AB  - A new algorithm for the clock frequency prediction used to calculate the Echelle
      Atomique Libre (EAL) is presented. The mathematical model adopted in the new
      prediction algorithm takes into account the effect of the frequency drift of the
      H-masers. We demonstrate that there is an improvement in long-term stability of
      EAL by using the new prediction algorithm.

PMID- 20040441
TI  - Improving TWSTFT short-term stability by network time transfer.
AB  - Two-way satellite time and frequency transfer (TWSTFT) is one of the major
      techniques to compare the atomic time scales between timing laboratories. As more
      and more TWSTFT measurements have been performed, the large number of point-to
      point 2-way time transfer links has grown to be a complex network. For future
      improvement of the TWSTFT performance, it is important to reduce measurement
      noise of the TWSTFT results. One method is using TWSTFT network time transfer.
      The Asia-Pacific network is an exceptional case of simultaneous TWSTFT
      measurements. Some indirect links through relay stations show better shortterm
      stabilities than the direct link because the measurement noise may be neutralized
      in a simultaneous measurement network. In this paper, the authors propose a
      feasible method to improve the short-term stability by combining the direct and
      indirect links in the network. Through the comparisons of time deviation (TDEV),
      the results of network time transfer exhibit clear improved short-term
      stabilities. For the links used to compare 2 hydrogen masers, the average gain of
      TDEV at averaging times of 1 h is 22%. As TWSTFT short-term stability can be
      improved by network time transfer, the network may allow a larger number of
      simultaneously transmitting stations.

PMID- 20040442
TI  - Coherent microwave transfer over a 204-km telecom fiber link by a cascaded
      system.
AB  - We have demonstrated a microwave transfer over a 204-km noisy urban fiber link by
      a cascaded system with 2 stages, which connected 10-GHz and 1-GHz transfer
      systems in series. A diurnal phase-noise cancellation ratio of 45 dB was obtained
      by use of an electronic phase-noise compensation system. Additionally, the
      stabilities reached 6 x 10(-14) at 1 s and 5 x 10(-17) at one-half day, which
      agreed with the root-sum-square of those of the 10-GHz and 1-GHz transfers. We
      verified for the first time that the transfer stability degrades only square root
      N times in a cascaded system with N stages.

PMID- 20040443
TI  - Phase-coherent frequency comparison of optical clocks using a telecommunication
      fiber link.
AB  - We have explored the performance of 2 "dark fibers" of a commercial
      telecommunication fiber link for a remote comparison of optical clocks. These
      fibers establish a network in Germany that will eventually link optical frequency
      standards at PTB with those at the Institute of Quantum Optics (IQ) at the
      Leibniz University of Hanover, and the Max Planck Institutes in Erlangen (MPL)
      and Garching (MPQ). We demonstrate for the first time that within several minutes
      a phase coherent comparison of clock lasers at the few 10(-15) level can also be
      accomplished when the lasers are more than 100 km apart. Based on the performance
      of the fiber link to the IQ, we estimate the expected stability for the link from
      PTB to MPQ via MPL that bridges a distance of approximately 900 km.

PMID- 20040444
TI  - The dynamic Allan variance II: a fast computational algorithm.
AB  - The stability of an atomic clock can change with time due to several factors,
      such as temperature, humidity, radiations, aging, and sudden breakdowns. The
      dynamic Allan variance, or DAVAR, is a representation of the time-varying
      stability of an atomic clock, and it can be used to monitor the clock behavior.
      Unfortunately, the computational time of the DAVAR grows very quickly with the
      length of the analyzed time series. In this article, we present a fast algorithm
      for the computation of the DAVAR, and we also extend it to the case of missing
      data. Numerical simulations show that the fast algorithm dramatically reduces the
      computational time. The fast algorithm is useful when the analyzed time series is
      long, or when many clocks must be monitored, or when the computational power is
      low, as happens onboard satellites and space probes.

PMID- 20040445
TI  - Ultrasonic probes having three orthogonal polarizations.
AB  - Ultrasonic probes which can simultaneously generate and receive 2 orthogonal
      polarized shear (S(perpendicular) and S(//)) and longitudinal (L) waves in screw
      shape have been presented. Thick piezoelectric films are directly fabricated onto
      the heads of such probes as L wave integrated ultrasonic transducers.
      S(perpendicular) and S(//) waves are obtained using mode conversion method.
      Potential applications of such probes are discussed.

PMID- 20040446
TI  - Microbubble characterization through acoustically induced deflation.
AB  - Ultrasound contrast agents (UCA) populations are typically polydisperse and
      contain microbubbles with radii over a given range. Although the behavior of
      microbubbles of certain sizes might be masked by the behavior of others, the
      acoustic characterization of UCA is typically made on full populations. In this
      paper, we have combined acoustic and optical methods to investigate the response
      of isolated lipid-shelled microbubbles to low-pressure (49 and 62 kPa peak
      negative pressure) ultrasound tone bursts. These bursts induced slow deflation of
      the microbubbles. The experimental setup included a microscope connected to a
      fast camera acquiring one frame per pulse transmitted by a single-element
      transducer. The behavior of each bubble was measured at multiple frequencies, by
      cyclically changing the transmission frequency over the range of 2 to 4 MHz
      during subsequent pulse repetition intervals. The bubble echoes were captured by
      a second transducer and coherently recorded. More than 50 individual microbubbles
      were observed. Microbubbles with radii larger than 3 mum did not experience any
      size reduction. Smaller bubbles slowly deflated, generally until the radius
      reached a value around 1.4 microm, independent of the initial microbubble size.
      The detected pressure amplitude backscattered at 2.5 cm distance was very low,
      decreasing from about 5 Pa down to 1 Pa at 2 MHz as the bubbles deflated. The
      resonant radius was evaluated from the echo amplitude normalized with respect to
      the geometrical cross section. At 2-MHz excitation, deflating microbubbles showed
      highest normalized echo when the radius was 2.2 microm while at higher excitation
      frequencies, the resonant radius was lower. The relative phase shift of the echo
      during the deflation process was also measured. It was found to exceed pi/2 in
      all cases. A heuristic procedure based on the analysis of multiple bubbles of a
      same population was used to estimate the undamped natural frequency. It was found
      that a microbubble of 1.7 microm has an undamped natural frequency of 2 MHz. The
      difference between this size and the resonant radius is discussed as indicative
      of significant damping.

PMID- 20040447
TI  - Assessment of arterial distension based on continuous wave Doppler ultrasound
      with an improved Hilbert-Huang processing.
AB  - A novel approach based on continuous wave (CW) Doppler ultrasound and the Hilbert
      Huang transform with end-effect restraint by mirror extending is proposed to
      assess arterial distension. In the approach, bidirectional Doppler signals were
      first separated using the phasing-filter technique from the mixed quadrature
      Doppler signals, which were produced by bidirectional blood and vessel wall
      movements. Each separated unidirectional signal was decomposed into intrinsic
      mode functions (IMFs) using the empirical mode decomposition with end effect
      restraint by mirror extending algorithm, and then the relevant IMFs that
      contribute to the vessel wall components were identified. Finally, the
      displacement waveforms of the vessel wall were calculated by integrating its
      moving velocity waveforms, which were extracted from the bidirectional Hilbert
      spectrum estimated from the identified wall IMFs. This approach was applied to
      simulated and clinical Doppler signals from normal common carotid arteries
      (CCAs). In the simulation study, the estimated wall moving velocity and
      displacement waveforms were compared with the theoretical ones, respectively. The
      mean and standard deviation of the root-mean-square errors between the estimated
      and theoretical wall distension of the 30 realizations was 4.2 +/- 0.4 microm. In
      the clinical study, peak-to-peak distension was extracted in a subject and then
      averaged over 15 cardiac cycles, resulting in 603 +/- 22 microm. The mean and
      standard deviation of the CCA distension averaged over the experimental
      measurements of 12 healthy subjects gave the result of 620 +/- 154 microm. The
      clinical results were in agreement with those measured by using the multigate
      Doppler ultrasound and echo tracking systems. The results show that based on the
      CW Doppler ultrasound, the proposed approach is practical for extracting arterial
      wall peak-to-peak distension correctly and could be an alternative method for the
      vessel wall distension estimation.

PMID- 20040448
TI  - A model of distributed phase aberration for deblurring phase estimated from
      scattering.
AB  - Correction of aberration in ultrasound imaging uses the response of a point
      reflector or its equivalent to characterize the aberration. Because a point
      reflector is usually unavailable, its equivalent is obtained using statistical
      methods, such as processing reflections from multiple focal regions in a random
      medium. However, the validity of methods that use reflections from multiple
      points is limited to isoplanatic patches for which the aberration is essentially
      the same. In this study, aberration is modeled by an offset phase screen to relax
      the isoplanatic restriction. Methods are developed to determine the depth and
      phase of the screen and to use the model for compensation of aberration as the
      beam is steered. Use of the model to enhance the performance of the noted
      statistical estimation procedure is also described. Experimental results obtained
      with tissue-mimicking phantoms that implement different models and produce
      different amounts of aberration are presented to show the efficacy of these
      methods. The improvement in b-scan resolution realized with the model is
      illustrated. The results show that the isoplanatic patch assumption for
      estimation of aberration can be relaxed and that propagation-path characteristics
      and aberration estimation are closely related.

PMID- 20040449
TI  - Development of dual PZT transducers for reference-free crack detection in thin
      plate structures.
AB  - A new Lamb-wave-based nondestructive testing (NDT) technique, which does not rely
      on previously stored baseline data, is developed for crack monitoring in plate
      structures. Commonly, the presence of damage is identified by comparing "current
      data" measured from a potentially damaged stage of a structure with "baseline
      data" previously obtained at the intact condition of the structure. In practice,
      structural defects typically take place long after collection of the baseline
      data, and the baseline data can be also affected by external loading, temperature
      variations, and changing boundary conditions. To eliminate the dependence on the
      baseline data comparison, the authors previously developed a reference-free NDT
      technique using 2 pairs of collocated lead zirconate titanate (PZT) transducers
      placed on both sides of a plate. This reference-free technique is further
      advanced in the present study by the necessity of attaching transducers only on a
      single surface of a structure for certain applications such as aircraft. To
      achieve this goal, a new design of PZT transducers called dual PZT transducers is
      proposed. Crack formation creates Lamb wave mode conversion due to a sudden
      thickness change of the structure. This crack appearance is instantly detected
      from the measured Lamb wave signals using the dual PZT transducers. This study
      also suggests a reference-free statistical approach that enables damage
      classification using only the currently measured data set. Numerical simulations
      and experiments were conducted using an aluminum plate with uniform thickness and
      fundamental Lamb waves modes to demonstrate the applicability of the proposed
      technique to reference-free crack detection.

PMID- 20040450
TI  - Effect of ultrasonic capillary dynamics on the mechanics of thermosonic ball
      bonding.
AB  - Microelectronic wire bonding is an essential step in today's microchip
      production. It is used to weld (bond) microwires to metallized pads of integrated
      circuits using ultrasound with hundreds of thousands of vibration cycles.
      Thermosonic ball bonding is the most popular variant of the wire bonding process
      and frequently investigated using finite element (FE) models that simplify the
      ultrasonic dynamics of the process with static or quasistatic boundary
      conditions. In this study, the ultrasonic dynamics of the bonding tool
      (capillary), made from Al(2)O(3), is included in a FE model. For more accuracy of
      the FE model, the main material parameters are measured. The density of the
      capillary was measured to be rho(cap) = 3552 +/- 100 kg/m(3). The elastic modulus
      of the capillary, E(cap) = 389 +/- 11 GPa, is found by comparing an auxiliary FE
      model of the free vibrating capillary with measured values. A capillary "nodding
      effect" is identified and found to be essential when describing the ultrasonic
      vibration shape. A main FE model builds on these results and adds bonded ball,
      pad, chip, and die attach components. There is excellent agreement between the
      main model and the ultrasonic force measured at the interface on a test chip with
      stress microsensors. Bonded ball and underpad stress results are reported. When
      adjusted to the same ultrasonic force, a simplified model without ultrasonic
      dynamics and with an infinitely stiff capillary tip is substantially off target
      by -40% for the maximum underpad stress. The compliance of the capillary causes a
      substantial inclination effect at the bonding interface between wire and pad.
      This oscillating inclination effect massively influences the stress fields under
      the pad and is studied in more detail. For more accurate results, it is therefore
      recommended to include ultrasonic dynamics of the bonding tool in mechanical FE
      models of wire bonding.

PMID- 20040451
TI  - An ultrasonic air pump using an acoustic traveling wave along a small air gap.
AB  - An ultrasonic air pump that uses a traveling wave along a small air gap between a
      bending vibrator and a reflector is discussed. The authors investigate ultrasonic
      air pumps that make use of bending vibrators and reflectors and confirm that air
      can be induced to flow by generating an asymmetric acoustic standing wave along
      an air gap. In this paper, we proposed a novel ultrasonic air pump in which a
      traveling wave along an air gap induces acoustic streaming and achieves one-way
      airflow. Two new reflector configurations, stepped and tapered, were designed and
      used to generate traveling waves. To predict airflow generation, sound pressure
      distribution in the air gap was calculated by means of finite element analysis
      (FEA). As a preliminary step, 2 FEA models were compared: one piezoelectric
      structure-acoustic model and one piezoelectric- structure-fluid model, which
      included the viscosity effect of the fluid. The sound pressure distribution in
      the air gap, including fluid viscosity, was calculated by the FEA because it is
      expected to be dominant and thus have a strong effect on the sound pressure field
      in such a thin fluid layer. Based on the FEA results of the stepped and the
      tapered reflectors, it was determined that acoustic traveling waves could
      propagate along the gaps. Experiments were carried out with the designed bending
      vibrator and the reflectors. The acoustic fields in the air gap were measured via
      a fiber optic probe, and it was determined that the sound pressure and the phase
      distribution tendencies corresponded well with the results computed by FEA.
      Through our experiments, one-way airflow generation, in the same direction of the
      traveling wave and with the maximum flow velocity of 5.6 cm/s, was achieved.

PMID- 20040452
TI  - Multilevel nonuniform grid algorithm for acceleration of integral equation-based
      solvers for acoustic scattering.
AB  - A fast algorithm for the evaluation of acoustic fields produced by given source
      distributions is developed with the aim of accelerating iterative boundary
      element method (BEM) solvers. The algorithm is based on field smoothing by phase
      and amplitude compensation, which allows for sampling of the fields radiated by
      finite-size source distributions over coarse nonuniform (spherical) grids (NGs).
      Subsequently, the fields at the desired target points can be obtained by an
      interpolation and phase and amplitude restoration. Combining this approach with
      the divide-and-conquer strategy, the total field is computed via a hierarchical
      decomposition of the source domain. In this computational scheme, the phase and
      amplitude compensated fields produced by neighboring subdomains are gradually
      aggregated through a multilevel process involving interpolation between
      increasingly dense NGs and the scatterer surface. This multilevel NG algorithm is
      used to reduce the computational cost of applying the field evaluation operator
      and its adjoint, as required in each iteration of the conjugate gradient solver
      based on the BEM-discretized integral representation of scattering problems.
      Accuracy and computational efficiency of the NG algorithm are demonstrated on
      representative examples of elongated, quasi-planar, and full 3-D scatterers.

PMID- 20040453
TI  - It is time to deal with latent tuberculosis infection in Taiwan.

PMID- 20040455
TI  - Effects of supplementary private health insurance on physician visits in Korea.
AB  - BACKGROUND/PURPOSE: The coverage of social health insurance has remained limited,
      despite it being compulsory in Korea. Accordingly, Koreans have come to rely upon
      supplementary private health insurance (PHI) to cover their medical costs. We
      examined the effects of supplementary PHI on physician visits in Korea. METHODS:
      This study used individual data from 11,043 respondents who participated in the
      Korean Labor and Income Panel Survey in 2001. We conducted a single probit model
      to identify the relationship between PHI and physician visits, with adjustment
      for the following covariates: demographic characteristics, socioeconomic status,
      health status, and health-related behavior. Finally, we performed a bivariate
      probit model to examine the true effect of PHI on physician visits, with
      adjustment for the above covariates plus unobservable covariates that might
      affect not only physician visit, but also the purchase of PHI. RESULTS: We found
      that about 38% of all respondents had one or more private health plans. Forty
      five percent of all respondents visited one or more physicians, and 49% of those
      who were privately insured had physician visits compared with 42% of the
      uninsured. The single probit model showed that those with PHI were about 14
      percentage points more likely to visit physicians than those who do not have PHI.
      However, this distinction disappears in the bivariate probit model. This result
      might have been a consequence of the nature of private health plans in Korea.
      Private insurance companies pay a fixed amount directly to their enrollees in
      case of illness/injury, and the individuals are responsible subsequently for
      purchasing their own healthcare services. CONCLUSION: This study demonstrated the
      potential of Korean PHI to address the problem of moral hazard. These results
      serve as a reference for policy makers when considering how to finance healthcare
      services, as well as to contain healthcare expenditure.

PMID- 20040454
TI  - Suppression of genomic instabilities caused by chromosome mis-segregation: a
      perspective from studying BubR1 and Sgo1.
AB  - Aneuploidy is a major manifestation of chromosomal instability, which is defined
      as a numerical abnormality of chromosomes in diploid cells. It is highly
      prevalent in a variety of human malignancies. Increased chromosomal instability
      is the major driving force for tumor development and progression. To suppress
      genomic stability during cell division, eukaryotic cells have evolved important
      molecular mechanisms, commonly referred to as checkpoints. The spindle checkpoint
      ensures that cells with defective mitotic spindles or a defective interaction
      between the spindles and kinetochores do not initiate chromosomal segregation
      during mitosis. Extensive studies have identified and characterized more than a
      dozen genes that play important roles in the regulation of the spindle checkpoint
      in mammalian cells. During the past decade, we have carried out extensive
      investigation of the role of BubR1 (Bub1-related kinase) and Sgo1 (shugoshin 1),
      two important gene products that safeguard accurate chromosome segregation during
      mitosis. This mini-review summarizes our studies, as well as those by other
      researchers in the field, on the functions of these two checkpoint proteins and
      their molecular regulation during mitosis. Further elucidation of the molecular
      mechanisms of the spindle checkpoint regulation has the potential to identify
      important mitotic targets for rational anticancer drug design.

PMID- 20040456
TI  - Hyperuricemia associated with rapid renal function decline in elderly Taiwanese
      subjects.
AB  - BACKGROUND/PURPOSE: Hyperuricemia is encountered frequently in patients with
      chronic kidney disease (CKD). We tested the hypothesis that uric acid influences
      glomerular filtration rate (GFR) and is associated with renal function decline in
      elderly Taiwanese subjects. METHODS: We enrolled 800 elderly Taiwanese subjects
      for a health checkup. Estimated GFR (eGFR) was measured using the Modification of
      Diet in Renal Disease Study equation. eGFR < 60 mL/min/1.73 m2 was used to
      analyze the prevalence and incidence of CKD. Significant renal function decline
      was defined as a decrease in eGFR of > or = 3 mL/min/1.73 m2 per year. RESULTS:
      The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid
      level was 6.6 mg/dL in male and 5.6 mg/dL in female subjects, and eGFR was 71.7
      mL/min/1.73 m2. Uric acid levels were associated independently and negatively
      with eGFR after adjusting for conventional factors of renal function decline. One
      hundred and sixty-two individuals (31.2%) had a significant decline in renal
      function. As uric acid level increased by 1 mg/dL, the odds of a significant eGFR
      decline increased by 1.208. CONCLUSION: Serum uric acid level was associated with
      eGFR and decline in renal function in elderly Taiwanese subjects. Whether
      hypouricemic therapy could retard the progression of CKD deserves further in
      depth study.

PMID- 20040457
TI  - Prevalence of Helicobacter pylori infection in high-school students on Lanyu
      Island, Taiwan: risk factor analysis and effect on growth.
AB  - BACKGROUND/PURPOSE: The Yami inhabit Lanyu Island and are the smallest and most
      primitive aboriginal tribe in Taiwan. Lanyu Island is a closed environment and
      little information is available on the prevalence of Helicobacter pylori
      infection there. This study aimed to establish the prevalence of H. pylori
      infection in high-school students on Lanyu Island and its risk factors and effect
      on growth. METHODS: A cross-sectional population-based study was conducted among
      high-school students to determine the prevalence of H. pylori infection by using
      the 13C urea breath test. A questionnaire was administered to the recruited
      population. Relevant personal and socioeconomic data for risk factors of
      infection were collected. Body height and weight of the recruited adolescents in
      relation to H. pylori infection were analyzed. RESULTS: A total of 106 high
      school students (55 boys and 51 girls), with a mean age of 14.3 +/- 1.4 years
      were enrolled. The overall prevalence of H. pylori infection was 54.7%. Those
      residing in Dongcing village had the highest rate of H. pylori infection (73.3%).
      There was no difference in the prevalence of H. pylori infection according to
      sex, ethnicity, socioeconomic level or parental education. Sixty-two students
      (54.8%) were completely asymptomatic and the others had at least one
      gastrointestinal symptom. H. pylori infection was asymptomatic in 56.8% and
      symptomatic in 53.2% of students. There was no significant difference between
      infected and uninfected children with regard to body weight, height and body mass
      index. CONCLUSION: The prevalence of H. pylori infection is high among high
      school students on Lanyu Island. There is no evidence that infection is related
      to growth failure.

PMID- 20040458
TI  - Hearing in noise test in subjects with conductive hearing loss.
AB  - BACKGROUND/PURPOSE: It has been reported that patients with pure conductive
      hearing loss (CHL) have remarked that their hearing is better in the presence of
      background noise. This study investigated the ability for speech discrimination
      under background noise in adult subjects with CHL, using the Mandarin Hearing in
      Noise Test (M-HINT). METHODS: Seventeen subjects with unilateral CHL and 15 with
      bilateral CHL participated in this study. Twenty normal-hearing subjects served
      as controls. During the M-HINT, the sentences and noise were presented in a
      soundproof chamber. Reception threshold for sentences (RTS) in quiet were
      obtained first, and then three more blocks, including noise from the front, right
      and left, were measured for each subject. RESULTS: The RTS in quiet was
      significantly elevated in unilateral and bilateral CHL groups. For the unilateral
      group, regardless of whether noise came from the front, affected side, or normal
      side, the signal-tonoise ratio (SNR) that was needed to reach 50% correction was
      significantly higher than in the control group. For the bilateral group, the SNR
      for noise from the front, left and right was significantly elevated compared with
      that in the unilateral and control groups. The noise composite score was also
      significantly different among these three groups (control < unilateral <
      bilateral). CONCLUSION: There was reduced speech discrimination ability under
      background noise in adult subjects with unilateral or bilateral CHL.

PMID- 20040459
TI  - Frontalis suspension using expanded polytetrafluoroethylene: results of different
      surgical designs.
AB  - BACKGROUND/PURPOSE: Several surgical designs and materials have been proposed for
      frontalis suspension for treating congenital ptosis and ptosis with poor levator
      muscle function. This study evaluated the surgical results of frontalis
      suspension using expanded polytetrafluoroethylene (ePTFE) with two different
      surgical designs (open-type and closed-type). METHODS: We reviewed the medical
      records of 96 patients (68 children and 28 adults) who underwent frontalis
      suspension surgery using ePTFE. Postoperative eyelid position, ptosis recurrence,
      and complications were recorded. RESULTS: Twenty-eight out of 68 children and all
      28 adults underwent closed-type frontalis suspension surgery, and 40 children
      underwent open-type surgery. The recurrence rate was 20% (8 of 40 eyelids) for
      children with closed-type surgery, and 2% (1 of 50 eyelids) for those with open
      type surgery. There was a statistically significant difference in the recurrence
      rate between the two surgical methods in children (p = 0.011). The recurrence
      rate was 5% (2 of 40 eyelids) in adults who underwent the closed-type method. The
      recurrence rate after closed-type surgery was significantly different between the
      child and adult groups (p = 0.04). CONCLUSION: Open-type frontalis suspension
      surgery using ePTFE is preferable to closed-type surgery for children with upper
      eyelid ptosis. Closed-type surgery provides more favorable results in adults than
      in children.

PMID- 20040460
TI  - Botulinum toxin A injection to the bladder neck and urethra for medically
      refractory lower urinary tract symptoms in men without prostatic obstruction.
AB  - BACKGROUND/PURPOSE: Lower urinary tract symptoms (LUTS) in men with small benign
      prostatic hyperplasia (BPH) might not result from prostatic compression. Instead,
      bladder neck and urethral dysfunction could play an important role. We
      investigated the effect of botulinum toxin A (BoNT-A) injection to the bladder
      neck and urethra of men with small BPH and LUTS that were refractory to medical
      treatment. METHODS: We enrolled 30 men with a total prostate volume (TPV) of < 40
      mL, International Prostate Symptom Score (IPSS) > 12, and maximum urinary flow
      rate (Qmax) < 15 mL/second, who were refractory to medical treatment. None had
      bladder outlet obstruction upon videourodynamic study. One hundred units of BoNT
      A dissolved in 10 mL normal saline was injected at 10 sites at the trigone,
      bladder neck, proximal urethra, distal urethra and external sphincter. The values
      for IPSS, quality of life (QoL) index, Qmax, bladder capacity, post-void residual
      (PVR), TPV and global satisfaction at 1, 3 and 6 months after injection were
      compared with baseline. RESULTS: Significant improvements in empty and total IPSS
      were found at 1 and 3 months but not 6 months after treatment. Qmax significantly
      increased at 1 month and was still improved at 6 months. Bladder capacity
      increased and PVR decreased at 1 and 3 months but not at 6 months after
      treatment. QoL index and global satisfaction were improved significantly at all
      time points after treatment. CONCLUSION: Bladder neck and urethral BoNT-A
      injections improved LUTS and increased Qmax in men with a small prostate. Our
      findings suggest that bladder neck and urethral dysfunction may play a role in
      LUTS in men without BPH.

PMID- 20040461
TI  - Pediatric reference intervals for several biochemical analytes in school children
      in Central Taiwan.
AB  - BACKGROUND/PURPOSE: Reference intervals of biochemical tests for screening for
      diabetes mellitus and liver and renal function among school children in Central
      Taiwan have never been documented. Therefore, this study aimed to establish the
      reference intervals for the above mentioned biochemical tests for pediatric
      populations. METHODS: A total of 4326 subjects, including 2029 kindergarten
      children, 1624 elementary-school children, 325 junior-high-school children, and
      348 teachers were selected randomly in Central Taiwan. All serum alanine
      aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (Cr) and glucose
      levels were determined using a Beckman Synchron CX5 analyzer. The reference
      intervals reflected estimates of the 2.5th-97.5th percentiles of non-parametric
      distributions. RESULTS: Adults had significantly higher biochemical analyte
      values [except for BUN/creatinine (B/C) ratio] than children had. Multiple
      logistic regression analysis showed that biochemical analyte values were
      significantly higher in male than in female subjects. The concentrations of
      glucose and Cr increased with age. On the contrary, the B/C ratio decreased with
      age. CONCLUSION: Our study provides new pediatric reference intervals (2.5th
      97.5th percentiles) of 60-99 mg/dL for serum glucose concentrations, 8-38 IU/L
      for ALT, 0.4-1.1 mg/L for Cr, 8.7-18.0 mg/L for BUN, and 10-34 for B/C ratio. The
      B/C ratio in children was higher than those of adults, possibly due to that
      children had a higher intake of protein.

PMID- 20040462
TI  - Eosinophilic cellulitis after honeybee sting.
AB  - Stings by honeybees are not uncommon and most cases cause pain but no significant
      medical problems. Some patients, however, have lethal complications such as acute
      anaphylactic shock. Cellulitis caused by honeybee sting is very rare and can be a
      late complication in some patients. We report a 45-year-old female patient who
      was stung by a honeybee, and whose right forearm showed progressive swelling with
      bullous formation after the sting. She was sent to our emergency department with
      the diagnosis of right hand cellulitis. After treatment with antibiotics for 5
      days, the lesions showed no response. Then, systemic steroid was used and the
      lesion gradually resolved. Diagnosis of Wells syndrome was made according to
      clinical appearance, course and characteristic histopathological findings.

PMID- 20040463
TI  - Ring keratitis associated with topical abuse of a dilute anesthetic after
      refractive surgery.
AB  - Anesthetic toxic keratitis is rare and presents as a ring keratitis, which is
      often misdiagnosed as Acanthamoeba keratitis. Here, we report an unusual case of
      toxic keratitis caused by topical abuse of a dilute anesthetic. A 26-year-old
      woman presented with bilateral corneal edema, ring infiltrates, pigmented keratic
      precipitate, Descemets membrane folding, and strong anterior chamber reactions 2
      weeks after laser subepithelial keratomileusis surgery. Tracing back her medical
      history, topical dilute 0.1% proparacaine was prescribed and frequently used for
      1 month. Toxic keratitis was suspected. After discontinuation of the topical
      anesthetic and initiation of treatment with topical 20% autologous serum,
      complete corneal epithelialization was achieved within 1 week. Corneal
      infiltrates and anterior chamber reaction gradually subsided. Vision improved
      from finger counting to 20/20 in the right eye and 20/25 in the left eye, but
      confocal microscopy showed decreased corneal endothelial cells. Topical abuse of
      a dilute topical anesthetic can cause severe toxic keratitis and endothelial cell
      loss. The physician must be aware of the signs of topical anesthetic abuse and
      should not prescribe even a dilute anesthetic for long-term use. Autologous serum
      can help in the recovery of toxic keratitis.

PMID- 20040464
TI  - Timing and mode of surgery for inflammatory omental cyst questioned.

PMID- 20040466
TI  - Gefitinib as first-line therapy for advanced or metastatic non-small cell lung
      cancer patients in southern Taiwan.
AB  - Gefitinib, a selective epidermal growth factor receptor tyrosine kinase
      inhibitor, is effective in treating patients with non-small cell lung cancer
      (NSCLC) after unsuccessful chemotherapy. However, survival outcomes and
      predictors for its effectiveness in chemotherapy-naive NSCLC patients are still
      not clear. The goal of this study was to investigate the response and survival
      rates and identify the predictive factors for patients with advanced or
      metastatic disease receiving gefitinib as first-line therapy. We retrospectively
      analyzed the response and survival rates of patients with advanced or metastatic
      NSCLC who had received gefitinib as first-line therapy across six medical
      institutes in Southern Taiwan between May 2004 and April 2006. The relationship
      between the response and survival rates to the known predictive factors for
      gefitinib response and survival was also investigated. A total of 97 patients (65
      females and 32 males) were enrolled in this study. Seventy-four patients (76%)
      had never smoked. Eighty-eight patients (91%) had adenocarcinoma or
      bronchioloalveolar cell carcinoma. The objective response rate was 56% and the
      disease control rate (partial response plus stable disease) was 76%. Only poor
      performance status (Eastern Cooperative Oncology Group score, 3-4) was
      statistically significantly associated with overall response in this study. The 1
      year survival rate was 77%. We suggest that first-line gefitinib monotherapy is
      promising in some subgroups of Asian patients with NSCLC. Further randomized
      controlled studies are needed to validate the effectiveness of first-line
      gefitinib therapy.

PMID- 20040467
TI  - Lower plasma neuropeptide Y level in patients with atypical febrile convulsions.
AB  - Febrile convulsion (FC) is the most common neurological disease in children.
      Cases with seizures that persist for more than 15 minutes or recurrent seizures
      within the same febrile illness are considered to be atypical and may have a
      different prognosis. Neuropeptide Y (NPY), an endogenous anticonvulsant that is
      widely distributed throughout the central nervous system, including the
      hippocampus, is known to prevent seizures by increasing the seizure threshold.
      Based on our previously finding that patients with atypical FC have lower
      concentrations of NPY, we hypothesized that the concentration of NPY may play a
      role in the development of atypical FC. To investigate this hypothesis, we used a
      radioimmunoassay to measure the plasma NPY concentration of 60 children with FC
      (typical FC, n = 46; atypical FC, n = 14) and 56 age-matched controls. The
      atypical FC group had significantly lower concentrations of NPY than children
      with typical FC and controls (66.47 +/- 19.11 pmol/L vs. 88.68 +/- 28.50 pmol/L
      and 86.82 +/- 22.66 pmol/L, respectively). Very low NPY levels were found in two
      patients; one patient (NPY level: 44.75 pmol/L) experienced prolonged seizures
      lasting for up to 1 hour and the other had recurrent seizures (three seizures)
      during the same febrile illness (NPY level: 33.53 pmol/L). These results suggest
      that patients with inadequate NPY inhibitory activity are more susceptible to
      atypical FC.

PMID- 20040468
TI  - Correlations between quality of life and psychological factors in patients with
      chronic neck pain.
AB  - The purpose of this study was to investigate health-related quality of life
      (HRQOL) and associated factors in patients with chronic neck pain (CNP). The
      HRQOL of patients with CNP was assessed by the Short Form-36 questionnaire in
      this cross-sectional study. To evaluate the psychological factors related to
      HRQOL, the Eysenck Personality Questionnaire, Chinese Health Questionnaire, and
      Beck Anxiety Inventory were used. The scores for the eight subscales of Short
      Form-36 were all lower than the Taiwanese age-matched normative values (p <
      0.001). The two most strongly affected subscales were the role-physical subscale
      and the bodily pain subscale; both scores were below half the score of the age
      /sex-matched normative values. The physical components summary score, a summary
      measure, was moderately correlated with age (rho = -0.43), education level (rho =
      0.37) and Beck Anxiety Inventory score (rho = -0.36). The mental components
      summary score was moderately to highly correlated with the Chinese Health
      Questionnaire score (rho = -0.72), the neuroticism domain of Eysenck Personality
      Questionnaire (rho = -0.52) and Beck Anxiety Inventory score (rho = -0.41). The
      HRQOL of patients with CNP was worse than that of normal subjects across all
      domains. Furthermore, patients with a neurotic personality, minor psychiatric
      morbidity and higher anxiety status showed poor mental health, as measured by the
      Short Form-36. We found that patients with CNP had multiple physical and mental
      health problems in terms of. The mental health of patients with CNP was strongly
      associated with various psychological factors. Comprehensive assessment of the
      physical and mental functioning of patients with CNP can improve the management
      and care of these patients.

PMID- 20040469
TI  - Quantitative assessment of image quality in 64-slice-computed tomography of
      coronary arteries in subjects undergoing screening for coronary artery disease.
AB  - Accurate and consistent visualization of the entire coronary system with high
      grade imaging quality is crucial for routine applications of multi-detector
      computed tomography (MDCT) coronary angiography. To determine the imaging quality
      of 64-slice-MDCT coronary angiography, we respectively explored the quantitative
      parameters of imaging quality in 105 consecutive subjects (71 men, 34 women; aged
      58.66 +/- 10.62 years) who underwent 64-slice-MDCT coronary angiography to screen
      for coronary disease. The interobserver agreement for semi-quantitative image
      quality, visible length, signal-to-noise ratio (SNR) and contrast-to-noise ratio
      (CNR) of the coronary arteries was good. The SNR and CNR of the proximal segments
      of the coronary arteries were superior to that of the distal segments of coronary
      arteries (p < 0.001). The visible length of the stenosed right coronary artery
      was significantly shorter than that of the non-stenosed right coronary artery (p
      = 0.03). The SNR and CNR of the stenosed and non-stenosed coronary arteries
      revealed no significant difference (p > 0.05). Body weight and body mass index
      were inversely related to the SNR and CNR of the aorta (p < 0.001). In
      conclusion, 64-slice-MDCT coronary angiography can provide excellent imaging
      quality of coronary arteries in subjects undergoing screening for coronary
      disease, although the SNR and CNR were relatively low at the distal segments of
      coronary arteries.

PMID- 20040470
TI  - Congenital seminal vesicle cyst associated with ipsilateral renal agenesis
      mimicking bladder outlet obstruction: a case report and review of the literature.
AB  - Seminal vesicle cysts combined with genitourinary anomalies are uncommon. We
      present a 43-year-old married man who suffered from difficulty in urination and
      irritating voiding symptoms for 3 years. The symptoms worsened in the last 6
      months. Digital rectal examination revealed a palpable large soft mass behind the
      prostate. Diagnostic imaging showed a left seminal vesicle cyst with an
      intravesical protrusion. The ipsilateral kidney and ureter were absent.
      Transrectal aspiration of the cyst was performed, which improved the clinical
      genitourinary symptoms. The maximal and mean urinary flow rates increased from 18
      to 37 mL/s and from 6 to 16 mL/s, respectively.

PMID- 20040471
TI  - Medical treatment of a Salmonella-infected left ventricular pseudoaneurysm: a
      case report.
AB  - Here, we present a case of Salmonella infection in a post-myocardial infarction
      patient with a left ventricular aneurysm and mural thrombus. This is a rare case
      that was successfully treated with medicinal therapy alone. Our experience with
      this case documents the early spontaneous drainage of the myocardial abscess by 8
      weeks of antibiotic therapy under serial two- and three-dimensional
      echocardiography to monitor the clinical outcomes and guide the decision-making
      process. This approach may be a viable alternative for intolerant, high-risk
      surgical aneurysmectomy patients.

PMID- 20040472
TI  - Colonic metastasis from a primary adenocarcinoma of the lung presenting with
      acute abdominal pain: a case report.
AB  - Colonic metastasis from lung cancer is rare and generally asymptomatic. Here, we
      report a case with lung adenocarcinoma that presented with acute abdominal pain
      due to intestinal obstruction caused by the metastatic colon tumor. The patient
      underwent emergency colonoscopy and the pathologic report was adenocarcinoma,
      which was the same as that for a bronchoscopic biopsy from a large lung mass.
      Immunohistochemistry was positive for thyroid transcription factor-1 and
      cytokeratin 7, and negative for cytokeratin 20 and caudal-related homeobox
      transcription factor 2 on both lung biopsy and colon surgical specimens.
      Accordingly, we used immunohistochemistry for thyroid transcription factor-1,
      cytokeratin 7, cytokeratin 20 and caudal-related homeobox transcription factor-2
      to diagnose primary adenocarcinoma of the lung with colonic metastasis.

PMID- 20040473
TI  - Co-existence of posttraumatic empyema thoracis and lung abscess in a child after
      blunt chest trauma: a case report.
AB  - Posttraumatic empyema is a rare complication of trauma with an incidence of 1.6
      2.4% in trauma patients. However, it is rarely reported in children. We report
      the case of a 15-year-old boy who was involved in a traffic accident and
      diagnosed with a pulmonary contusion at a local hospital. Fourteen days after the
      accident, posttraumatic empyema thoracis and lung abscess developed with clinical
      presentations of fever, productive cough and right chest pain. He was
      successfully treated with computed tomography-guided catheter drainage and
      intravenous cefotaxime. We emphasize that posttraumatic empyema thoracis and lung
      abscess are very rare in children, and careful follow-up for posttraumatic lung
      contusion is essential. Image-guided catheter drainage can be an adjunctive tool
      for treating selected patients, although most complicated cases of posttraumatic
      empyema thoracis require decortication therapy.

PMID- 20040474
TI  - Intraoperative fluorescence imaging during surgery for coronary artery fistula.
AB  - A 45-year-old man had a history of myocardial infarction at one month prior to
      admission. Coronary angiography revealed a dilated fistula originating from the
      left anterior descending coronary artery to the pulmonary artery. Two orifices of
      the draining artery were closed through pulmonary arteriotomy. Ligation of the
      fistulous vessels was performed at three places to ensure complete closure of the
      fistula. Before and after the cardiopulmonary bypass, fluorescent dye angiography
      was performed with indocyanine green. Fluorescence imaging revealed complete
      closure of the fistula and no residual shunt flow. Postoperative coronary
      angiography revealed neither a residual fistula nor injury to the coronary
      artery.

PMID- 20040475
TI  - Giant thymoma in the anterior-inferior mediastinum.
AB  - Thymomas are usually found in the superior mediastinum and sternotomy is the
      standard approach for resection. We report a case of a male patient with a giant
      left-sided thymoma, nearly fulfilling the whole hemithorax. Due to the sheer size
      of the tumor and its location in the anterior-inferior mediastinum, we performed
      a lateral approach for thymectomy. On resection the specimen measured 18 x 16 x
      12 cm. Histology revealed a mixed stage I thymoma. The patient is doing well 36
      months after resection and has no signs of recurrence. In literature, a
      significant increase in the risk of recurrence for thymomas >8 cm is reported.

PMID- 20040476
TI  - Unusual primary pleural leiomyoma.
AB  - Primary pleural leiomyoma is extremely rare and has only been described a few
      times. We present a case of a young woman with right pleuritic pain. A computed
      tomography confirmed the existence of a solid right pleural tumor which had
      compressed and displaced the lung, mediastinum and heart. Percutaneous biopsy
      showed a 'proliferation of smooth muscle cells without evidence of malignancy'.
      Surgical excision was done and the tumor was not associated to vascular, broncho
      pulmonary or mediastinal structures. The definitive diagnosis was primary pleural
      leiomyoma. Primary pleural leiomyoma should be included in a differential
      diagnosis of pleural tumors and suspected in asymptomatic patients with
      radiologically-apparent benign tumors and the presence of smooth muscle fibers in
      the biopsy. Complete resection and follow-up is advised because it can grow very
      large and has malignant potential.

PMID- 20040477
TI  - The rupture of descending thoracic aorta due to the necrosis of aortic intimal
      sarcoma.
AB  - Aortic intimal sarcoma is rare and the prognosis is very poor. We experienced a
      case of ruptured aortic intimal sarcoma in the descending aorta. A 69-year-old
      man underwent an emergency operation for the rupture of descending aorta. The
      postoperative course was uneventful. The histological examination of aortic wall
      showed aortic intimal sarcoma. The patient developed a local recurrence and
      abdominal dissemination of the tumor three months after surgery. We report the
      case and discuss about the diagnosis and treatment of thoracic aortic intimal
      sarcoma.

PMID- 20040478
TI  - New approach to reduce allograft tissue immunogenicity. Experimental data.
AB  - OBJECTIVES: Rejection is thought to contribute to the degeneration of valved
      allografts. Most proposed methods of decellularisation allow usage of treated
      valves in pulmonic position. We developed a new protocol of devitalization, which
      provides cell death and suppression of calcification using digitonin and
      ethylenediaminetetraacetic acid. The aim of the study was to evaluate new
      allografts in a chronic canine model. METHODS: Two groups of adult mongrel dogs
      (5 in each) were used for allograft implantation. The cryopreserved viable (group
      1) and devitalized (group 2) heart valve aorta allografts were tested. Allografts
      were implanted as valved patches into the thoracic aorta and explanted after four
      months. Histologic examination and fluorescence microscopy were used to test
      tissue matrix and cells in allografts. Mineralized calcium in the samples was
      detected using absorption spectroscopy. RESULTS: The fluorescence microscopy
      proved that a significant number of cells were viable in the allografts after
      their cryopreservation (group 1) and all the cells were dead after anticalcinosis
      devitalisation (group 2). No damage of tissue matrix was observed in group 2
      after devitalisation. After explantation, the cusps in both groups were either
      stuck to aorta wall of the allografts, or there were thrombus clots between the
      cusps and the wall. Internal surface was covered with neointima. Media of aortic
      wall was acellular. Repopulation of the viable and devitalized tissues with
      recipient cells during a 4-month follow-up period was not observed. In non
      treated allografts, aortic walls had areas of dissection and infiltration of
      lymphoid cells. Devitalized patches were homogenous without dissection areas.
      There was no immune-cell infiltration in devitalized matrix as opposed to
      cryopreserved vital tissue. CONCLUSIONS: The new devitalizing technology seems
      effective in decreasing immune response to homologous tissue. It does not affect
      elasto-mechanic properties and collagenous structure of allografts. The presented
      data stimulate interest to the anticalcinosis devitalisation technology as an
      affective tool for improving biocompatibility of allografts.

PMID- 20040479
TI  - Reopening acutely occluded cavopulmonary connections in infants and children.
AB  - Little is known about the outcome of acute thrombotic occlusion of segments of
      the cavopulmonary connections (CPC) in infants and children with univentricular
      hearts. Early recognition and aggressive therapy may result in successful salvage
      of some of these patients. Five consecutive patients (age range 4-8 months)
      presenting with acute occlusion of a CPC segment underwent emergency cardiac
      catheterization. After angiographic confirmation, the occluded segment was
      crossed using an endhole catheter and guidewire combination. Serial balloon
      dilation and stent implantation (ten stents in total) were undertaken to
      recanalize the occlusion. The stents used were mounted on balloons ranging in
      diameter from 6 mm to 8 mm, depending on the size of the native vessel. The sites
      of occlusion were the left pulmonary artery (n=4), and the left-sided superior
      caval vein (n=3). All occlusions could be successfully recanalized. In three
      patients, early reocclusion necessitated either surgery or repeat catheterization
      and angioplasty. There were two early deaths, due to recurrent thrombotic
      obstruction confirmed either at autopsy or angiography. The remaining patients
      are alive and well; the majority of survivors have undergone completion of the
      Fontan operation. A high index of clinical suspicion combined with aggressive
      therapy can result in successful recanalization in some infants with acutely
      occluded CPC segments, with acceptable long-term outcome.

PMID- 20040480
TI  - Inflammatory myofibroblastic tumour at the pacemaker site.
AB  - Inflammatory myofibroblastic tumour (IMT) or inflammatory pseudotumour is a
      histologically distinctive lesion occurring primarily in the viscera and soft
      tissue of children and young adults. We report an unusual case of IMT which had
      undergone malignant transformation in the chest wall at the pacemaker site. A 64
      year-old male presented with a history of high fever, loss of appetite and weight
      loss of three months duration. He had a dual chamber pacemaker reinserted in the
      left infraclavicular region in the previous year. This was followed by a
      gradually enlarging hard swelling at the insertion site. The CT-scan showed a
      soft tissue mass encasing the pacing box, without intrathoracic extension. The
      trucut biopsy was suspicious of soft tissue sarcoma. A well encapsulated hard
      mass, with pacemaker embedded within it was resected en-bloc ensuring wide
      resection margins. Histology revealed fascicles of spindle cell proliferation
      with prominent inflammatory component, occasional spindle cells with prominent
      nucleoli and scattered atypical mitotic figures, with areas of focal necrosis.
      The lesional cells were negative for CD21, smooth muscle actin, ckit,
      cytokeratins and anaplastic lymphoma kinase 1. A diagnosis of IMT with malignant
      transformation i.e. inflammatory fibrosarcoma was made. He had adjuvant
      radiotherapy and uneventful recovery.

PMID- 20040481
TI  - PKCdelta blues for the beta-cell.

PMID- 20040482
TI  - The final frontier: how does diabetes affect the brain?

PMID- 20040483
TI  - Exhaled nitric oxide in the diagnosis of childhood asthma.

PMID- 20040484
TI  - Medicine and the Media. Thyroxine: anatomy of a health scare.

PMID- 20040485
TI  - Pattern formation in miniature: the female gametophyte of flowering plants.
AB  - Plant reproduction involves gamete production by a haploid generation, the
      gametophyte. For flowering plants, a defining characteristic in the evolution
      from the 'naked-seed' plants, or gymnosperms, is a reduced female gametophyte,
      comprising just seven cells of four different types--a microcosm of pattern
      formation and gamete specification about which only little is known. However,
      several genes involved in the differentiation, fertilization and post
      fertilization functions of the female gametophyte have been identified and,
      recently, the morphogenic activity of the plant hormone auxin has been found to
      mediate patterning and egg cell specification. This article reviews recent
      progress in understanding the pattern formation, maternal effects and evolution
      of this essential unit of plant reproduction.

PMID- 20040486
TI  - Drosophila Hey is a target of Notch in asymmetric divisions during embryonic and
      larval neurogenesis.
AB  - bHLH-O proteins are a subfamily of the basic-helix-loop-helix transcription
      factors characterized by an 'Orange' protein-protein interaction domain. Typical
      members are the Hairy/E(spl), or Hes, proteins, well studied in their ability,
      among others, to suppress neuronal differentiation in both invertebrates and
      vertebrates. Hes proteins are often effectors of Notch signalling. In
      vertebrates, another bHLH-O protein group, the Hey proteins, have also been shown
      to be Notch targets and to interact with Hes. We have studied the single
      Drosophila Hey orthologue. We show that it is primarily expressed in a subset of
      newly born neurons, which receive Notch signalling during their birth. Unlike in
      vertebrates, however, Hey is not expressed in precursor cells and does not block
      neuronal differentiation. It rather promotes one of two alternative fates that
      sibling neurons adopt at birth. Although in the majority of cases Hey is a Notch
      target, it is also expressed independently of Notch in some lineages, most
      notably the larval mushroom body. The availability of Hey as a Notch readout has
      allowed us to study Notch signalling during the genesis of secondary neurons in
      the larval central nervous system.

PMID- 20040488
TI  - A planarian p53 homolog regulates proliferation and self-renewal in adult stem
      cell lineages.
AB  - The functions of adult stem cells and tumor suppressor genes are known to
      intersect. However, when and how tumor suppressors function in the lineages
      produced by adult stem cells is unknown. With a large population of stem cells
      that can be manipulated and studied in vivo, the freshwater planarian is an ideal
      system with which to investigate these questions. Here, we focus on the tumor
      suppressor p53, homologs of which have no known role in stem cell biology in any
      invertebrate examined thus far. Planaria have a single p53 family member, Smed
      p53, which is predominantly expressed in newly made stem cell progeny. When Smed
      p53 is targeted by RNAi, the stem cell population increases at the expense of
      progeny, resulting in hyper-proliferation. However, ultimately the stem cell
      population fails to self-renew. Our results suggest that prior to the
      vertebrates, an ancestral p53-like molecule already had functions in stem cell
      proliferation control and self-renewal.

PMID- 20040487
TI  - Rfx6 is an Ngn3-dependent winged helix transcription factor required for
      pancreatic islet cell development.
AB  - The transcription factor neurogenin 3 (Neurog3 or Ngn3) controls islet cell fate
      specification in multipotent pancreatic progenitor cells in the mouse embryo.
      However, our knowledge of the genetic programs implemented by Ngn3, which control
      generic and islet subtype-specific properties, is still fragmentary. Gene
      expression profiling in isolated Ngn3-positive progenitor cells resulted in the
      identification of the uncharacterized winged helix transcription factor Rfx6.
      Rfx6 is initially expressed broadly in the gut endoderm, notably in Pdx1-positive
      cells in the developing pancreatic buds, and then becomes progressively
      restricted to the endocrine lineage, suggesting a dual function in both endoderm
      development and islet cell differentiation. Rfx6 is found in postmitotic islet
      progenitor cells in the embryo and is maintained in all developing and adult
      islet cell types. Rfx6 is dependent on Ngn3 and acts upstream of or in parallel
      with NeuroD, Pax4 and Arx transcription factors during islet cell
      differentiation. In zebrafish, the Rfx6 ortholog is similarly found in
      progenitors and hormone expressing cells of the islet lineage. Loss-of-function
      studies in zebrafish revealed that rfx6 is required for the differentiation of
      glucagon-, ghrelin- and somatostatin-expressing cells, which, in the absence of
      rfx6, are blocked at the progenitor stage. By contrast, beta cells, whose number
      is only slightly reduced, were no longer clustered in a compact islet. These data
      unveil Rfx6 as a novel regulator of islet cell development.

PMID- 20040489
TI  - Nodal and BMP2/4 pattern the mesoderm and endoderm during development of the sea
      urchin embryo.
AB  - Nodal factors play fundamental roles in induction and patterning of the mesoderm
      and endoderm in vertebrates, but whether this reflects an ancient role or one
      that evolved recently in vertebrates is not known. Here, we report that in
      addition to its primary role in patterning the ectoderm, sea urchin Nodal is
      crucial for patterning of the endoderm and skeletogenic mesoderm through the
      regulation of the expression of key transcription factors and signalling
      molecules, including BMP2/4 and FGFA. In addition, we uncovered an essential role
      for Nodal and BMP2/4 in the formation and patterning of the non-skeletogenic
      mesoderm. By comparing the effects of misexpressing Nodal or an activated Nodal
      receptor in clones of cells, we provide evidence that Nodal acts over a long
      range in the endomesoderm and that its effects on the blastocoelar cell
      precursors are likely to be direct. The activity of Nodal and BMP2/4 are
      antagonistic, and although bmp2/4 is transcribed in the ventral ectoderm
      downstream of Nodal, the BMP2/4 ligand is translocated to the dorsal side, where
      it activates signalling in the dorsal primary mesenchyme cells, the dorsal
      endoderm and in pigment cell precursors. Therefore, correct patterning of the
      endomesoderm depends on a balance between ventralising Nodal signals and
      dorsalising BMP2/4 signals. These experiments confirm that Nodal is a key
      regulator of dorsal-ventral polarity in the sea urchin and support the idea that
      the ventral ectoderm, like the Spemann organiser in vertebrates, is an organising
      centre that is required for patterning all three germ layers of the embryo.

PMID- 20040490
TI  - Regulation of cortical contractility and spindle positioning by the protein
      phosphatase 6 PPH-6 in one-cell stage C. elegans embryos.
AB  - Modulation of the microtubule and the actin cytoskeleton is crucial for proper
      cell division. Protein phosphorylation is known to be an important regulatory
      mechanism modulating these cytoskeletal networks. By contrast, there is a
      relative paucity of information regarding how protein phosphatases contribute to
      such modulation. Here, we characterize the requirements for protein phosphatase
      PPH-6 and its associated subunit SAPS-1 in one-cell stage C. elegans embryos. We
      establish that the complex of PPH-6 and SAPS-1 (PPH-6/SAPS-1) is required for
      contractility of the actomyosin network and proper spindle positioning. Our
      analysis demonstrates that PPH-6/SAPS-1 regulates the organization of cortical
      non-muscle myosin II (NMY-2). Accordingly, we uncover that PPH-6/SAPS-1
      contributes to cytokinesis by stimulating actomyosin contractility. Furthermore,
      we demonstrate that PPH-6/SAPS-1 is required for the proper generation of pulling
      forces on spindle poles during anaphase. Our results indicate that this
      requirement is distinct from the role in organizing the cortical actomyosin
      network. Instead, we uncover that PPH-6/SAPS-1 contributes to the cortical
      localization of two positive regulators of pulling forces, GPR-1/2 and LIN-5. Our
      findings provide the first insights into the role of a member of the PP6 family
      of phosphatases in metazoan development.

PMID- 20040491
TI  - Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation.
AB  - Tgif1 and Tgif2 are transcriptional co-repressors that limit the response to
      TGFbeta signaling and play a role in regulating retinoic-acid-mediated gene
      expression. Mutations in human TGIF1 are associated with holoprosencephaly, but
      it is unclear whether this is a result of deregulation of TGFbeta/Nodal
      signaling, or of effects on other pathways. Surprisingly, mutation of Tgif1 in
      mice results in only relatively mild developmental phenotypes in most strain
      backgrounds. Here, we show that loss-of-function mutations in both Tgif1 and
      Tgif2 result in a failure of gastrulation. By conditionally deleting Tgif1 in the
      epiblast, we demonstrate that a single wild-type allele of Tgif1 in the extra
      embryonic tissue allows the double null embryos to gastrulate and begin
      organogenesis, suggesting that extra-embryonic Tgif function is required for
      patterning the epiblast. Genetically reducing the dose of Nodal in embryos
      lacking all Tgif function results in partial rescue of the gastrulation defects.
      Conditional double null embryos have defects in left-right asymmetry, which are
      also alleviated by reducing the dose of Nodal. Together, these data show that
      Tgif function is required for gastrulation, and provide the first clear evidence
      that Tgifs limit the transcriptional response to Nodal signaling during early
      embryogenesis.

PMID- 20040492
TI  - VEGF is required for dendritogenesis of newly born olfactory bulb interneurons.
AB  - The angiogenic factor vascular endothelial growth factor A (VEGF) has been shown
      to have a role in neurogenesis, but how it affects adult neurogenesis is not
      fully understood. To delineate a role for VEGF in successive stages of olfactory
      bulb (OB) neurogenesis, we used a conditional transgenic system to suppress VEGF
      signaling at the adult mouse sub-ventricular zone (SVZ), rostral migratory stream
      (RMS) and OB, which constitute the respective sites of birth, the migration
      route, and sites where newly born interneurons mature and integrate within the
      existing OB circuitry. Following the development of fluorescently tagged adult
      born neurons, we show that sequestration of VEGF that is constitutively expressed
      by distinct types of resident OB neurons greatly impaired dendrite development in
      incoming SVZ-born neurons. This was evidenced by reduced dendritic spine density
      of granule cells and significantly shorter and less branched dendrites in
      periglomerular neurons. Notably, the vasculature and perfusion of the SVZ, RMS
      and OB were not adversely affected when VEGF suppression was delayed until after
      birth, thus uncoupling the effect of VEGF on dendritogenesis from its known role
      in vascular maintenance. Furthermore, a requirement for VEGF was specific to
      newly born neurons, as already established OB neurons were not damaged by VEGF
      inhibition. This study thus uncovered a surprising perfusion-independent role of
      VEGF in the adult brain, namely, an essential role in the maturation of adult
      born neurons.

PMID- 20040493
TI  - The transcriptional co-factor Chip acts with LIM-homeodomain proteins to set the
      boundary of the eye field in Drosophila.
AB  - Development involves the establishment of boundaries between fields specified to
      differentiate into distinct tissues. The Drosophila larval eye-antennal imaginal
      disc must be subdivided into regions that differentiate into the adult eye,
      antenna and head cuticle. We have found that the transcriptional co-factor Chip
      is required for cells at the ventral eye-antennal disc border to take on a head
      cuticle fate; clones of Chip mutant cells in this region instead form outgrowths
      that differentiate into ectopic eye tissue. Chip acts independently of the
      transcription factor Homothorax, which was previously shown to promote head
      cuticle development in the same region. Chip and its vertebrate CLIM homologues
      have been shown to form complexes with LIM-homeodomain transcription factors, and
      the domain of Chip that mediates these interactions is required for its ability
      to suppress the eye fate. We show that two LIM-homeodomain proteins, Arrowhead
      and Lim1, are expressed in the region of the eye-antennal disc affected in Chip
      mutants, and that both require Chip for their ability to suppress photoreceptor
      differentiation when misexpressed in the eye field. Loss-of-function studies
      support the model that Arrowhead and Lim1 act redundantly, using Chip as a co
      factor, to prevent retinal differentiation in regions of the eye disc destined to
      become ventral head tissue.

PMID- 20040496
TI  - FGF signaling directs a center-to-pole expansion of tubulogenesis in mouse testis
      differentiation.
AB  - In mouse embryogenesis, Sry is transiently activated in a center-to-pole wavelike
      manner along the anteroposterior (AP) axis of developing XY gonads. However, the
      mechanism and significance of the center-to-pole expansion of testis initiation
      pathways downstream of Sry expression remain unclear. Here we demonstrate that
      FGF9 can act as a diffusible conductor for a poleward expansion of tubulogenic
      programs at early phases of testis differentiation. In XY genital ridge cultures
      of anterior, middle and posterior segments at 11.0-11.25 days post-coitum, male
      specific activation of Sry and its target gene, Sox9, was still observed in both
      anterior and posterior pole segments despite their isolation from the central
      domain. However, high-level Sox9 expression was not maintained, resulting in the
      failure of testis cord organization in most pole segments. A reconstruction
      experiment using ROSA:lacZ middle segments showed rescue of the tubulogenic
      defect in the poles without any appreciable contribution of lacZ-positive gonadal
      parenchyma cells. A partition culture assay also showed a possible contribution
      of soluble/diffusible factors secreted from the gonadal center domain to proper
      tubulogenesis in the poles. Among various signaling factors, Fgf9 expression was
      significantly lower in both anterior and posterior pole segments than in the
      central domain. The supportive role of the central domain could be substituted by
      exogenous FGF9 supply, whereas reduction of Wnt4 activity did not rescue the
      tubulogenesis defect in the pole segments. These observations imply that center
      to-pole FGF9 diffusion directs a poleward expansion of testiculogenic programs
      along the AP axis of developing XY gonads.

PMID- 20040494
TI  - Non-cell-autonomous retinoid signaling is crucial for renal development.
AB  - In humans and mice, mutations in the Ret gene result in Hirschsprung's disease
      and renal defects. In the embryonic kidney, binding of Ret to its ligand, Gdnf,
      induces a program of epithelial cell remodeling that controls primary branch
      formation and branching morphogenesis within the kidney. Our previous studies
      showed that transcription factors belonging to the retinoic acid (RA) receptor
      family are crucial for controlling Ret expression in the ureteric bud; however,
      the mechanism by which retinoid-signaling acts has remained unclear. In the
      current study, we show that expression of a dominant-negative RA receptor in
      mouse ureteric bud cells abolishes Ret expression and Ret-dependent functions
      including ureteric bud formation and branching morphogenesis, indicating that RA
      receptor signaling in ureteric bud cells is crucial for renal development.
      Conversely, we find that RA-receptor signaling in ureteric bud cells depends
      mainly on RA generated in nearby stromal cells by retinaldehyde dehydrogenase 2,
      an enzyme required for most fetal RA synthesis. Together, these studies suggest
      that renal development depends on paracrine RA signaling between stromal
      mesenchyme and ureteric bud cells that regulates Ret expression both during
      ureteric bud formation and within the developing collecting duct system.

PMID- 20040495
TI  - Role of Fgf8 signalling in the specification of rostral Cajal-Retzius cells.
AB  - Cajal-Retzius (CR) cells play a key role in the formation of the cerebral cortex.
      These pioneer neurons are distributed throughout the cortical marginal zone in
      distinct graded distributions. Fate mapping and cell lineage tracing studies have
      recently shown that CR cells arise from restricted domains of the pallial
      ventricular zone, which are associated with signalling centres involved in the
      early regionalisation of the telencephalic vesicles. In this study, we identified
      a subpopulation of CR cells in the rostral telencephalon that expresses Er81, a
      downstream target of Fgf8 signalling. We investigated the role of the rostral
      telencephalic patterning centre, which secretes FGF molecules, in the
      specification of these cells. Using pharmacological inhibitors and genetic
      inactivation of Fgf8, we showed that production of Fgf8 by the rostral
      telencephalic signalling centre is required for the specification of the Er81+ CR
      cell population. Moreover, the analysis of Fgf8 gain-of-function in cultivated
      mouse embryos and of Emx2 and Gli3 mutant embryos revealed that ectopic Fgf8
      signalling promotes the generation of CR cells with a rostral phenotype from the
      dorsal pallium. These data showed that Fgf8 signalling is both required and
      sufficient to induce rostral CR cells. Together, our results shed light on the
      mechanisms specifying rostral CR cells and further emphasise the crucial role of
      telencephalic signalling centres in the generation of distinct CR cell
      populations.

PMID- 20040497
TI  - GFAPdelta in radial glia and subventricular zone progenitors in the developing
      human cortex.
AB  - A subpopulation of glial fibrillary acidic protein (GFAP)-expressing cells
      located along the length of the lateral ventricles in the subventricular zone
      (SVZ) have been identified as the multipotent neural stem cells of the adult
      mammalian brain. We have previously found that, in the adult human brain, a
      splice variant of GFAP, termed GFAPdelta, was expressed specifically in these
      cells. To investigate whether GFAPdelta is also present in the precursors of SVZ
      astrocytes during development and whether GFAPdelta could play a role in the
      developmental process, we analyzed GFAPdelta expression in the normal developing
      human cortex and in the cortex of foetuses with the migration disorder
      lissencephaly type II. We demonstrated for the first time that GFAPdelta is
      specifically expressed in radial glia and SVZ neural progenitors during human
      brain development. Expression of GFAPdelta in radial glia starts at around 13
      weeks of pregnancy and disappears before birth. GFAPdelta is continuously
      expressed in the SVZ progenitors at later gestational ages and in the postnatal
      brain. Co-localization with Ki67 proved that these GFAPdelta-expressing cells are
      able to proliferate. Furthermore, we showed that the expression pattern of
      GFAPdelta was disturbed in lissencephaly type II. Overall, these results suggest
      that the adult SVZ is indeed a remnant of the foetal SVZ, which develops from
      radial glia. Furthermore, we provide evidence that GFAPdelta can distinguish
      resting astrocytes from proliferating SVZ progenitors.

PMID- 20040499
TI  - DiSUMO-like DSUL is required for nuclei positioning, cell specification and
      viability during female gametophyte maturation in maize.
AB  - Reversible post-translational modification of numerous proteins by small
      ubiquitin-related modifiers (SUMOs) represents a major regulatory process in
      various eukaryotic cellular and developmental processes. To study the role of
      sumoylation during female gametophyte (FG) development in maize, we identified
      Zea mays genes encoding SUMO (ZmSUMO1a and ZmSUMO1b) and a diSUMO-like protein
      called ZmDSUL that contains two head-to-tail SUMO-like domains. Whereas ZmSUMO1a
      and ZmSUMO1b are almost ubiquitously expressed, ZmDSUL transcripts were detected
      exclusively in the egg apparatus and zygote. ZmDSUL was selected for detailed
      studies. ZmDSUL is processed close to the C-terminus, generating a dimeric
      protein that is similar to animal FAT10 and ISG15, which contain two ubiquitin
      like domains. Whereas GFP fused to the ZmDSUL N-terminus was located in the
      cytoplasm and predominately in the nucleoplasm of some transiently transformed
      maize suspension cells, C-terminal GFP fusions exclusively accumulated at the
      nuclear surface. GFP or ZmDSUL-GFP under control of the ZmDSUL promoter first
      displayed GFP signals in the micropylar-most position of the FG at stage 5/6,
      when migration of polar nuclei and cellularization occurs. Mature FGs displayed
      GFP signals exclusively in the egg cell, but the strongest signals were observed
      shortly after fertilization and disappeared during the first asymmetric zygotic
      division. RNAi silencing of ZmDSUL showed that it is required for FG viability.
      Moreover, nuclei segregation and positioning defects occurred at stage FG 5 after
      mitotic nuclear divisions were completed. In summary, we report a diSUMO-like
      protein that appears to be essential for nuclei segregation and positioning, the
      prerequisite for cell specification during FG maturation.

PMID- 20040498
TI  - Midline crossing by gustatory receptor neuron axons is regulated by fruitless,
      doublesex and the Roundabout receptors.
AB  - Although nervous system sexual dimorphisms are known in many species, relatively
      little is understood about the molecular mechanisms generating these dimorphisms.
      Recent findings in Drosophila provide the tools for dissecting how neurogenesis
      and neuronal differentiation are modulated by the Drosophila sex-determination
      regulatory genes to produce nervous system sexual dimorphisms. Here we report
      studies aimed at illuminating the basis of the sexual dimorphic axonal projection
      patterns of foreleg gustatory receptor neurons (GRNs): only in males do GRN axons
      project across the midline of the ventral nerve cord. We show that the sex
      determination genes fruitless (fru) and doublesex (dsx) both contribute to
      establishing this sexual dimorphism. Male-specific Fru (Fru(M)) acts in foreleg
      GRNs to promote midline crossing by their axons, whereas midline crossing is
      repressed in females by female-specific Dsx (Dsx(F)). In addition, midline
      crossing by these neurons might be promoted in males by male-specific Dsx
      (Dsx(M)). Finally, we (1) demonstrate that the roundabout (robo) paralogs also
      regulate midline crossing by these neurons, and (2) provide evidence that Fru(M)
      exerts its effect on midline crossing by directly or indirectly regulating Robo
      signaling.

PMID- 20040500
TI  - vHNF1 functions in distinct regulatory circuits to control ureteric bud branching
      and early nephrogenesis.
AB  - Mouse metanephric kidney development begins with the induction of the ureteric
      bud (UB) from the caudal portion of the Wolffian duct by metanephric mesenchymal
      signals. While the UB undergoes branching morphogenesis to generate the entire
      urinary collecting system and the ureter, factors secreted by the UB tips induce
      surrounding mesenchymal cells to convert into epithelia and form the nephrons,
      the functional units of the kidney. Epithelial branching morphogenesis and
      nephrogenesis are therefore tightly orchestrated; defects in either of these
      processes lead to severe kidney phenotypes ranging from hypoplasia to complete
      aplasia. However, the underlying regulatory networks have been only partially
      elucidated. Here, we identify the transcription factor vHNF1 (HNF1beta) as a
      crucial regulator of these early developmental events. Initially involved in
      timing outgrowth of the UB and subsequent branching, vHNF1 is also required for
      nephric duct epithelial maintenance, Mullerian duct formation and early
      nephrogenesis. Mosaic analyses further suggest a cell-autonomous requirement for
      vHNF1 in the acquisition of a specialized tip domain and branching morphogenesis.
      vHNF1 exerts these intricate functions at least in part through the direct
      control of key regulatory molecules involved in different aspects of early kidney
      development. Notably, vHNF1 acting directly upstream of Wnt9b appears to
      orchestrate Wnt signaling action in the mesenchymal-epithelial transitions
      underlying the initiation of nephrogenesis. These results demonstrate that vHNF1
      is an essential transcriptional regulator that, in addition to the known later
      functions in normal duct morphogenesis, plays a crucial role during the earliest
      stages of urogenital development and provide novel insights into the regulatory
      circuits controlling events.

PMID- 20040514
TI  - Sedentary lifestyle could be masking serious health problems in children.

PMID- 20040517
TI  - Identification and pharmacological properties of E339-3D6, the first nonpeptidic
      apelin receptor agonist.
AB  - Apelin plays a prominent role in body fluid and cardiovascular homeostasis. To
      explore further upstream the role played by this peptide, nonpeptidic agonists
      and antagonists of the apelin receptor are required. To identify such compounds
      that do not exist to date, we used an original fluorescence resonance energy
      transfer-based assay to screen a G-protein-coupled receptor-focused library of
      fluorescent compounds on the human EGFP-tagged apelin receptor. This led to
      isolated E339-3D6 that displayed a 90 nM affinity and behaved as a partial
      agonist with regard to cAMP production and as a full agonist with regard to
      apelin receptor internalization. Finally, E339-3D6 induced vasorelaxation of rat
      aorta precontracted with noradrenaline and potently inhibited systemic
      vasopressin release in water-deprived mice when intracerebroventricularly
      injected. This compound represents the first nonpeptidic agonist of the apelin
      receptor, the optimization of which will allow development of a new generation of
      vasodilator and aquaretic agents.

PMID- 20040515
TI  - KSHV downregulation of galectin-3 in Kaposi's sarcoma.
AB  - Galectins are a family of proteins that share an affinity for beta-galactoside
      containing glycoconjugates. In prostate, ovarian and breast cancer,
      downregulation of galectin-3 is associated with malignancy and tumor progression.
      Kaposi's sarcoma (KS) is characterized as an angioproliferative tumor of vascular
      endothelial cells and produces rare B cell lymphoproliferative diseases in the
      form of primary effusion lymphomas and some forms of multicentric Castleman's
      disease. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent
      of KS. We found reduced levels of galectin-3 expression in a significant fraction
      of latency-associated nuclear antigen (LANA)-positive spindle cell regions in
      human archival KS tissue and as measured in KS tissue microarrays. Here we
      demonstrate that galectin-3 protein expression is downregulated 10-fold in 10-day
      KSHV-infected dermal microvascular endothelial cells (DMVEC) accompanied by
      downregulation of message. There is loss of galectin-3 staining in KSHV-infected
      DMVEC by dual labeled immunohistochemistry in LANA-positive spindle cells. We
      observed a consistent downregulation of galectin-3 by time-course transcriptional
      analysis. Of the galectins assayed, only galectin-1 was also downregulated in
      KSHV-infected DMVEC. We examined 86 KS tumors; 19 were LANA positive (22%) and 67
      LANA negative (78%). All 86 tumors were found to be galectin-3 positive; 11 of 19
      showed reduced expression of galectin-3 in LANA-positive spindle cell regions.
      Our data suggest that KSHV vFLIP and LANA are the viral genes targeting galectin
      3 downregulation. The contribution of host factors to the pathogenesis of KS is
      essential for early detection and development of innovative therapies for
      treatment.

PMID- 20040516
TI  - Increased superoxide in vivo accelerates age-associated muscle atrophy through
      mitochondrial dysfunction and neuromuscular junction degeneration.
AB  - Oxidative stress has been implicated in the etiology of age-related muscle loss
      (sarcopenia). However, the underlying mechanisms by which oxidative stress
      contributes to sarcopenia have not been thoroughly investigated. To directly
      examine the role of chronic oxidative stress in vivo, we used a mouse model that
      lacks the antioxidant enzyme CuZnSOD (Sod1). Sod1(-/-) mice are characterized by
      high levels of oxidative damage and an acceleration of sarcopenia. In the present
      study, we demonstrate that muscle atrophy in Sod1(-/-) mice is accompanied by a
      progressive decline in mitochondrial bioenergetic function and an elevation of
      mitochondrial generation of reactive oxygen species. In addition, Sod1(-/-)
      muscle exhibits a more rapid induction of mitochondrial-mediated apoptosis and
      loss of myonuclei. Furthermore, aged Sod1(-/-) mice show a striking increase in
      muscle mitochondrial content near the neuromuscular junctions (NMJs). Despite the
      increase in content, the function of mitochondria is significantly impaired, with
      increased denervated NMJs and fragmentation of acetylcholine receptors. As a
      consequence, contractile force in aged Sod1(-/-) muscles is greatly diminished.
      Collectively, we show that Sod1(-/-) mice display characteristics of normal aging
      muscle in an accelerated manner and propose that the superoxide-induced NMJ
      degeneration and mitochondrial dysfunction are potential mechanisms of
      sarcopenia.

PMID- 20040518
TI  - The BRCA-1 binding protein BRAP2 is a novel, negative regulator of nuclear import
      of viral proteins, dependent on phosphorylation flanking the nuclear localization
      signal.
AB  - This study describes for the first time the ability of the novel BRCA1-binding
      protein 2 (BRAP2) to inhibit the nuclear import of specific viral proteins
      dependent on phosphorylation. Ectopic expression of BRAP2 in transfected African
      green monkey kidney COS-7 cells was found to significantly reduce nuclear
      localization signal (NLS)-dependent nuclear accumulation of either simian virus
      SV40 large-tumor antigen (T-ag) or human cytomegalovirus DNA polymerase
      processivity factor ppUL44; this was also observed in HL-60 human promyelocytic
      leukemia cells on induction of BRAP2 expression by vitamin D3 treatment. BRAP2
      inhibition of nuclear accumulation was dependent on phosphorylation sites
      flanking the respective NLSs, where substitution of the cyclin-dependent kinase
      site T124 of T-ag with Ala or Asp prevented or enhanced BRAP2 inhibition of
      nuclear import, respectively. Substitution of T427 within the NLS of ppUL44 gave
      similar results, whereas no effect of BRAP2 was observed on nuclear targeting of
      other viral proteins, such as herpes simplex virus-1 pUL30, which lacks a
      phosphorylation site near its NLS, and the human immunodeficiency virus-1 Tat
      protein. Pulldowns/AlphaScreen assays indicated direct, high-affinity binding of
      BRAP2(442-592) to T-ag(111-135), strictly dependent on negative charge at T124
      and the NLS. All results are consistent with BRAP2 being a novel, phosphorylation
      regulated negative regulator of nuclear import, with potential as an antiviral
      agent.

PMID- 20040519
TI  - A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the
      activated K+ channel voltage sensor.
AB  - The low-dielectric plasma membrane provides an energy barrier hindering
      transmembrane movement of charged particles. The positively charged, voltage
      sensing fourth transmembrane domain (S4) of voltage-gated ion channels must
      surmount this energy barrier to initiate channel activation, typically
      necessitating both membrane depolarization and interaction with membrane lipid
      phospho-head groups (MLPHGs). In contrast, and despite containing S4, the KCNQ1
      K(+) channel alpha subunit exhibits predominantly constitutive activation when in
      complexes with transmembrane beta subunits, MinK-related peptide (MiRP) 1 (KCNE2)
      or MiRP2 (KCNE3). Here, using a 2-electrode voltage clamp and scanning
      mutagenesis of channels heterologously expressed in Xenopus laevis oocytes, we
      discovered that 2 of the 8 MiRP2 extracellular domain acidic residues (D54 and
      D55) are important for KCNQ1-MiRP2 constitutive activation. Double-mutant
      thermodynamic cycle analysis revealed energetic coupling of D54 and D55 to R237
      in KCNQ1 S4 but not to 10 other native or introduced polar residues in KCNQ1 S4
      and surrounding linkers. MiRP2-D54 and KCNQ1-R237 also similarly dictated
      susceptibility to the inhibitory effects of MLPHG hydrolysis, whereas other
      closely situated polar residues did not. Thus, by providing negative charge near
      the plasma membrane extracellular face, MiRP2 uses a lipomimetic mechanism to
      constitutively stabilize the activated KCNQ1 voltage sensor.

PMID- 20040520
TI  - Increased mitochondrial content rescues in vivo muscle oxidative capacity in long
      term high-fat-diet-fed rats.
AB  - Mitochondria are thought to play a crucial role in the etiology of muscle insulin
      resistance (IR). The aim of this study was to gain more insight into the timing
      and nature of mitochondrial adaptations during the development of high-fat-diet
      (HFD)-induced IR. Adult Wistar rats were fed HFD or normal chow for 2.5 and 25
      wk. Intramyocellular lipids (IMCLs) were quantified in vivo using (1)H magnetic
      resonance spectroscopy (MRS). Muscle oxidative capacity was assessed in vivo
      using (31)P MRS and in vitro by measuring mitochondrial DNA copy number and
      oxygen consumption in isolated mitochondria. MRS in tibialis anterior muscle
      revealed 3.3-fold higher IMCL content and 1.2-fold increased oxidative capacity
      after 2.5 wk of HFD feeding. The latter result could be fully accounted for by
      increased mitochondrial content. After 25 wk of HFD, maximal ADP-stimulated
      oxygen consumption in isolated mitochondria oxidizing pyruvate plus malate
      remained unaffected, while IMCL and mitochondrial content had further increased
      compared to controls (5.1-fold and 1.4-fold, respectively). Interestingly, in
      vivo oxidative capacity at this time point was identical to controls. These
      results show that skeletal muscle in HFD-induced IR accompanied by IMCL
      accumulation requires a progressively larger mitochondrial pool size to maintain
      normal oxidative capacity in vivo.

PMID- 20040521
TI  - Environmental inequalities among children in Europe--evaluation of scientific
      evidence and policy implications.
AB  - BACKGROUND: Socio-economic inequalities in the living environment are major
      contributing factors to health inequalities. Consequently, protecting children
      from undesirable environmental exposures by taking socio-economic conditions into
      account has been identified as a policy priority area in Europe. This review aims
      to evaluate the evidence on environmental inequalities among children in Europe
      and to discuss its policy implications. METHODS: A systematic literature search
      was conducted in various literature databases. Further sources for information
      were reviews, international reports and working documents for a WHO expert
      meeting on environmental inequalities in 2009. One major inclusion criterion for
      publications was consideration of socio-economic factors as influencing factors,
      not merely as confounder. RESULTS: The overall pattern based on the available
      fragmentary data is that children living in adverse social circumstances suffer
      from multiple and cumulative exposures. A low socio-economic position is
      associated with an increased exposure of children to traffic-related air
      pollution, noise, lead, environmental tobacco smoke, inadequate housing and
      residential conditions and less opportunities for physical activity. For most
      topics and exposures reviewed here there were no studies investigating the
      modification of the exposure-response function by socio-economic factors. Due to
      a variety of methodological approaches and studies on one hand and lack of data
      for many topics and countries on the other hand it was not possible to quantify
      the magnitude of environmental inequalities. CONCLUSION: Action is needed along
      the whole causal pathway of the social divide in environmental hazards with
      priority to policy measures aiming at removing socially determined differences in
      environmental conditions.

PMID- 20040522
TI  - Migrants' utilization of somatic healthcare services in Europe--a systematic
      review.
AB  - BACKGROUND: Utilization of services is an important aspect of migrants' access to
      healthcare. The aim was to review the European literature on utilization of
      somatic healthcare services related to screening, general practitioner,
      specialist, emergency room and hospital by adult first-generation migrants. Our
      study question was: 'Are there differences in migrants' utilization of somatic
      healthcare services compared to non-migrants?' METHODS: Publications were
      identified by a systematic search of PUBMED and EMBASE. Appropriateness of the
      studies was judged independently by two researchers based on the abstracts.
      Additional searches were conducted via the references of the selected articles.
      The final number of studies included was 21. RESULTS: The results suggested a
      diverging picture regarding utilization of somatic healthcare services by
      migrants compared to non-migrants in Europe. Overall, migrants tended to have
      lower attendance and referral rates to mammography and cervical cancer screening,
      more contacts per patient to general practitioner but less use of consultation by
      telephone, and same or higher level of use of specialist care as compared to non
      migrants. Emergency room utilization showed both higher, equal and lower levels
      of utilization for migrants compared to non-migrants, whereas hospitalization
      rates were higher than or equal to non-migrants. CONCLUSION: Our review
      illustrates lack of appropriate epidemiological data and diversity in the
      categorization of migrants between studies, which makes valid cross-country
      comparisons most challenging. After adjusting for socio-economic factors and
      health status, the existing studies still show systematic variations in somatic
      healthcare utilization between migrants and non-migrants.

PMID- 20040523
TI  - Attenuated combined action of cyclosporine a and hyperlipidemia on atherogenesis
      in rabbits by thymoquinone.
AB  - This descriptive study investigates in a rabbit model of atherosclerosis (i) the
      extent of atherogenesis induced by cyclosporine A (CsA) or hyperlipidemia alone
      or in combination and (ii) whether thymoquinone (TQ), a known herbal antioxidant,
      offers protection against these effects. New Zealand White female rabbits were
      assigned to five groups of six animals each: Group I, control; Group II, CsA [25
      mg kg(-1) day(-1) orally (PO)]; Group III, 1% cholesterol; Group IV, 1%
      cholesterol + CsA (25 mg kg(-1) day(-1) PO); and Group V, 1% cholesterol + CsA
      (25 mg kg(-1) day(-1) PO) + TQ (10 mg kg(-1) day(-1) PO). Lipids and oxidative
      stress parameters [Malondialdehyde (MDA) and protein carbonyl] and aortic
      atherosclerosis were compared. CsA alone did not show a significant effect on
      either serum lipids and did not induce atherosclerosis. High-cholesterol diet
      induced atherosclerosis (45 +/- 11% of the intimal surface of aorta was covered
      with atherosclerotic plaques). CsA and high-cholesterol diet increased
      atherosclerosis severity as measured from intimal and media lesions, but did not
      affect the extent of atherosclerosis. TQ decreased aortic MDA by 83%. It was also
      associated with reduced aortic atherosclerosis extend by 52% compared with Group
      IV. We concluded that (i) CsA aggravates hyperlipidemia-induced atherosclerosis
      and (ii) TQ attenuates the oxidative stress and atherogenesis induced by the
      combined effect of CsA and hyperlipidemia.

PMID- 20040525
TI  - Analysis of 4-year Dutch reimbursement application data of biological therapies
      for psoriatic arthritis.
AB  - OBJECTIVES: To get the approval for reimbursement of biological therapies for
      PsA, patients need to fulfil specific criteria in many countries. The aim of this
      study was to evaluate the 4-year Dutch reimbursement application data, including
      the diagnostic, disease activity and response criteria that were applied for
      treatment of PsA with biologics. METHODS: All initial and follow-up applications
      for approval of treatment with biologics were included for investigation. Data
      were analysed descriptively with regard to application characteristics, patient
      characteristics and response to therapy. RESULTS: In the period studied, 3723
      application forms of 1991 patients were received. This concerned 2118 initial
      treatment applications and 1605 follow-up applications. Of all initial treatment
      applications, 2003 (94.6%) were approved. The major part of all applications
      concerned requests for etanercept (59.1%), followed by adalimumab (38.2%).
      Patients were suffering from polyarthritis in most cases (63.1%). MTX was used by
      nearly all patients, but only 55.8% had used the required dosage of 25 mg/week.
      Approximately 79.4% of all patients met the response criteria after 3 months of
      treatment. The mean number of affected joints declined from 7.7 at first
      application to 1.4 at follow-up. The initial visual analogue scale (VAS) score
      indicated by patients decreased from 71.2 to 24.1 at follow-up. The VAS score
      indicated by physicians decreased from 66.0 to 18.4. CONCLUSIONS: Biologics are
      expensive, but highly effective in the treatment of PsA. Careful compilation of
      treatment and reimbursement criteria is important for patients as well as for
      physicians and health insurance companies.

PMID- 20040524
TI  - RSC96 Schwann Cell Proliferation and Survival Induced by Dilong through PI3K/Akt
      Signaling Mediated by IGF-I.
AB  - Schwann cell proliferation is critical for the regeneration of injured nerves.
      Dilongs are widely used in Chinese herbal medicine to remove stasis and stimulate
      wound-healing functions. Exactly how this Chinese herbal medicine promotes tissue
      survival remains unclear. The aim of the present study was to investigate the
      molecular mechanisms by which Dilong promote neuron regeneration. Our results
      show that treatment with extract of Dilong induces the phosphorylation of the
      insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3
      kinase/serine-threonine kinase (PI3K/Akt) pathway, and activates protein
      expression of cell nuclear antigen (PCNA) in a time-dependent manner. Cell cycle
      analysis showed that G(1) transits into the S phase in 12-16 h, and S transits
      into the G(2) phase 20 h after exposure to earthworm extract. Strong expression
      of cyclin D1, cyclin E and cyclin A occurs in a time-dependent manner. Small
      interfering RNA (siRNA)-mediated knockdown of PI3K significantly reduced PI3K
      protein expression levels, resulting in Bcl(2) survival factor reduction and a
      marked blockage of G(1) to S transition in proliferating cells. These results
      demonstrate that Dilong promotes the proliferation and survival of RSC96 cells
      via IGF-I signaling. The mechanism is mainly dependent on the PI3K protein.

PMID- 20040526
TI  - Effect of the dual endothelin receptor antagonist bosentan on Raynaud's
      phenomenon secondary to systemic sclerosis: a double-blind prospective,
      randomized, placebo-controlled pilot study.
AB  - OBJECTIVE: To investigate the efficacy of the endothelin receptor antagonist,
      bosentan, in patients with RP secondary to SSc without pre-existing digital
      ulcers. METHODS: Single-centre, randomized, prospective, double-blinded
      comparison of bosentan and placebo. Patients received either 62.5 mg bosentan
      twice daily for 4 weeks, followed by 125 mg twice daily for 12 weeks or matching
      doses of placebo. RESULTS: Of the 17 patients enrolled, 16 completed the study
      and 1 withdrew from the study due to the reversible development of peripheral
      oedema. Compared with placebo, bosentan did not improve the frequency, duration,
      pain or severity of RP attacks. However, in contrast to placebo, bosentan
      significantly improved the functional scores. With respect to baseline, the
      scleroderma HAQ disability index changes were in favour of bosentan at Weeks 12
      (P = 0.03) and 20 (P = 0.01), and the United Kingdom functional score changes at
      Weeks 8 (P = 0.038) and 16 (P = 0.039). CONCLUSIONS: Bosentan is not effective in
      SSc-related RP without pre-existing digital ulcers, but it might benefit
      functional impairment in those patients. TRIAL REGISTRATION: European Union Drug
      Regulating Authorities Clinical Trials, https://eudract.emea.europa.eu, EudraCT
      Nr 2004-002686-21.

PMID- 20040527
TI  - Monitoring Achilles enthesitis in ankylosing spondylitis during TNF-alpha
      antagonist therapy: an ultrasound study.
AB  - OBJECTIVE: Enthesitis is considered as the primary anatomical lesion in
      ankylosing spondylitis (AS). Therapeutic effects of TNF-alpha antagonist
      treatments for enthesitis on imaging changes are still limited to case reports or
      small sample-sized trials. We aimed to investigate the potential of
      ultrasonography (US) to detect early changes after TNF-alpha antagonist therapy
      of Achilles enthesis of AS patients. METHODS: Forty-three AS patients with active
      disease, requiring TNF-alpha antagonist therapy, were included. Physical
      examination was performed to detect Achilles enthesitis and/or retrocalcaneal
      bursitis. US of the Achilles tendon was performed bilaterally. Grey-scale (GS)
      and power Doppler (PD) scores on a 0-2 semi-quantitative scale and total additive
      scores (TS) were calculated. Follow-up US examinations were performed 2 months
      after the initiation of therapy. RESULTS: At baseline, 11 patients (26.2%) were
      symptomatic in physical examination for either Achilles enthesitis or
      retrocalcaneal bursitis, whereas 36 (83%) had GS US pathological findings and 10
      (23.3%) had PD signal. GS score and TS decreased significantly [3.6 (3.0) vs 2.3
      (2.2), P < 0.001 and 4.7 (4.9) vs 2.7 (3.3), P < 0.001, respectively], whereas
      the decrease in PD score was not significant after 2 months of follow-up. The
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ESR and CRP levels
      also showed significant improvements. CONCLUSIONS: Subclinical Achilles
      enthesitis, detected only with GS US, is present in a subset of AS patients and a
      significant improvement can be demonstrated after 2 months of TNF-alpha
      antagonist therapy. In addition to standard outcome measures, US might be an
      additional useful tool to monitor therapy in SpA patients with Achilles
      enthesitis.

PMID- 20040528
TI  - Incidence of malignancy in primary Sjogren's syndrome in a Chinese cohort.
AB  - OBJECTIVES: To evaluate the incidence of malignancies in a cohort of Chinese
      patients with primary Sjogren's syndrome (pSS) and to identify the risk factors
      of malignancy in pSS patients. METHODS: A retrospective analysis was carried out
      in 1320 pSS patients who were recruited in Peking Union Medical College Hospital
      from 1990 to 2005 and were followed up for an average of 4.4 years. Among them,
      29 patients developed malignancies. Standardized incidence ratios (SIRs) were
      calculated along with 95% CIs. Clinical characteristics were compared between
      patients with and without malignancies, as well as patients with haematological
      and non-haematological tumours. RESULTS: Of the pSS patients, 2.2% developed
      malignancies during follow-up. Total SIR and SIR for lymphoma were 3.25 and 48.1,
      respectively. Different types of malignancy were observed including eight
      lymphomas, two myeloid myelomas and 19 solid tumours, which consisted of invasive
      thymoma, breast cancer, lung cancer, gastrointestinal adenocarcinoma, hepatoma,
      squamous cell carcinoma of tongue, uterine cervix cancer, renal carcinoma,
      thyroid carcinoma and mucoepidermoid carcinoma of parotid gland. Risk factor
      analysis showed that lymphadenopathy, enlargement of parotid glands, monoclonal
      immunoglobulin and absence of hypergammaglobulinaemia were correlated with
      malignancies. CONCLUSIONS: The current study confirms the increased incidence of
      lymphoma in Chinese patients with pSS, with the majority of B-cell non-Hodgkin's
      lymphoma. Associations between pSS and other malignant tumours such as myeloid
      myeloma, mouth cancer, breast cancer and thymoma need to be further observed.

PMID- 20040529
TI  - Patients' beliefs about the causes of systemic lupus erythematosus.
AB  - OBJECTIVE: Beliefs about the causes of SLE have rarely been investigated. The
      purpose of this study was to explore these beliefs. METHODS: Face-to-face
      interviews were carried out with a total of 33 women with SLE, fulfilling the ACR
      criteria, with a median age of 40 (range 15-65) years. Data were analysed using
      interpretative phenomenological analysis. RESULTS: Women attributed SLE to many
      causes, some of them being not congruent with biomedical models. The most
      frequent beliefs about the causes of SLE related to autoimmunity, psychological
      and familial causes, heredity, magico-religious causes (especially in first- and
      second-generation migrants) and infectious causes. Autoimmunity was often seen as
      a self-destructive process. CONCLUSIONS: Being diagnosed with SLE prompted 'Why
      me?' and 'Why now?' questioning among these women, who attempted to reconstruct
      coherence in their life histories. For clinicians, analysis of the beliefs about
      the causes clarifies what is at stake for the patient. The objective is to allow
      patients to produce narrative to describe their chronic illness experience in
      order to facilitate a long-term treatment alliance. Further studies are required
      to understand relationships between beliefs about causes, psychological distress
      and SLE morbidity.

PMID- 20040530
TI  - Differential effects of anti-TNF-alpha drugs on fibroblast-like synoviocyte
      apoptosis.
AB  - OBJECTIVE: Novel drugs targeting TNF-alpha are available for treatment of RA.
      Fibroblast-like synoviocytes (FLSs) play a fundamental role in RA progression,
      through their expansion caused in part by resistance to cell death induction. The
      aim of our study was to determine the effects of different anti-TNF-alpha agents
      on FLS apoptosis. METHODS: FLS from patients with either RA or OA were co
      cultured with peripheral blood mononuclear cells (PBMCs), and incubated with
      various drugs for 6 days. Subsequently, apoptosis induction was detected by
      Nucleosome ELISA and terminal deoxynucleotidyl transferase dUTP nick end
      labeling. Western blot was used to determine the activation of the phosphatase
      and tensin homologue deleted on chromosome 10 (PTEN)-focal adhesion kinase (FAK)
      pathway as well as Bax and Bcl-2 levels. Immunoprecipitation was used for
      studying phosphorylation of transmembrane TNF-alpha (tmTNF-alpha). RESULTS: All
      the tested drugs induced apoptosis of FLSs in the presence of PBMCs obtained from
      the same patient only when the two cell populations were in direct contact by
      activating the PTEN-FAK pathway and increasing Bax levels. This effect was not
      due to antibody-dependent cell-mediated cytotoxicity. Only the two antibodies
      infliximab and adalimumab were able to up-regulate Bcl-2. CONCLUSIONS: Etanercept
      is more effective in inducing FLS apoptosis compared with the other drugs tested.
      This induction is dependent on the presence of PBMCs, and involves the activation
      of PTEN-FAK pathway. Bcl-2 increase induced by the monoclonal antibodies
      infliximab and adalimumab may play a protective role and thus counteract their
      pro-apoptotic effect on FLSs.

PMID- 20040531
TI  - Re-classifying myositis.

PMID- 20040532
TI  - Low influenza vaccination rate among patients with systemic sclerosis.
AB  - OBJECTIVE: To evaluate the influenza vaccination rate and factors influencing it
      in patients with SSc. METHODS: A total of 177 SSc patients fulfilling the ACR
      and/or LeRoy and Medsger criteria were evaluated during annual meetings of the
      French patient association in 2006 (n = 71) and 2007 (n = 70) or during
      hospitalization in the Internal Medicine Department of Cochin Hospital in 2007 (n
      = 36). Information on influenza vaccination was collected by a standardized form.
      RESULTS: Mean (s.d.) age and disease duration were 58.7 (12.6) and 10.5 (9.5)
      years, respectively. Overall, 69 (39%) patients received an influenza vaccination
      during the previous year. Among the 108 patients who were not vaccinated, 78
      (72.2%) presented at least one indication for vaccination. The most frequent
      reasons for non-vaccination were absence of physician recommendation and fear of
      side effects. Patients who were and were not vaccinated did not differ in
      anxiety, depression, global disability or quality of life. Vaccination rate was
      significantly higher (59%) for patients who remembered receiving a letter from
      the French National Health Insurance Agency encouraging vaccination than among
      those who did not (26%, P = 0.0001). Multivariate analysis revealed the year of
      the last vaccination and age as two independent parameters associated with
      vaccination. CONCLUSIONS: Influenza vaccination coverage is low in SSc patients.
      Lack of information and fear of adverse effects are the most common reasons for
      non-vaccination. Efforts are needed to increase the influenza vaccination
      coverage in this population.

PMID- 20040533
TI  - Are clinical parameters and biomarkers predictive of severity of acute pulmonary
      emboli on CTPA?
AB  - BACKGROUND: Previous studies have shown that findings of computed tomography
      pulmonary angiography (CTPA) relate to outcome in pulmonary embolus (PE). These
      include clot burden as quantified using an obstruction index and markers of
      pressure overload such as right ventricle to left ventricle size ratio (RV/LV
      ratio). Little data exists correlating these findings with clinical presentation
      and biomarkers. AIM: To explore the link between clinical presentation and
      biomarkers with CTPA findings. METHODS: Retrospective case note analysis of
      consecutive cases presenting to a large teaching hospital. An independent
      radiologist reviewed CTPAs and clot burden quantified using an obstruction index.
      RESULTS: One hundred and seventy cases were identified and notes retrieved in 137
      cases. (i) CLINICAL PRESENTATION: correlation was seen between clot burden and
      systolic blood pressure (BP) (r = -0.299, P = 0.0006) and heart rate (r = 0.240,
      P = 0.0056). Median obstruction index was significantly higher in those with a
      presenting BP <90 mmHg [41.25% (95% CI 30-50) vs. 15% (95% CI 12.5-25), (P =
      0.0004)]. Clot burden was significantly higher in patients with temperature of
      >37.5 degrees C [30% (95% CI 25.0-42.5) vs. 15% (95% CI 12.5-28.3), P = 0.02)]
      and (ii)Biomarkers: significant correlation between clot burden and D-dimer was
      seen (r = 0.36, P = 0.0001). Location of thrombus was associated with significant
      differences in D-dimer level. A subgroup of patients had cardiac biomarkers
      measured (n = 24). There was a statistically significant correlation between
      troponin I and clot burden (r = 0.412, P = 0.048) and RV/LV ratio (r = 0.699, P =
      0.0013). DISCUSSION: These findings suggest that clinical parameters and
      biomarkers have a role in predicting the radiological severity of PE. These data
      support the need for further studies of risk stratification in patients
      presenting with acute PE.

PMID- 20040534
TI  - Barriers to targeted HIV testing on an acute admissions unit: evaluation of the
      UK guideline.
AB  - BACKGROUND: One-quarter of people living with human immunodeficiency virus (HIV)
      in the UK are unaware of their infection, leading to late presentation with
      consequent increased morbidity and mortality, as well as ongoing transmission of
      infection. Recent UK guidelines advise HIV testing of patients with 'indicator
      diseases' in secondary care. There are limited seroprevalence data to support
      this recommendation, and acute medical settings present operational difficulties
      that may limit its feasibility. METHODS: We conducted an audit of HIV testing
      rates over a 3-month period in an inner London acute admissions unit. RESULTS:
      Lower respiratory tract infection and fever were the most frequent indicator
      diseases. A total of 14% were known to be HIV positive on admission, indicating a
      high prevalence of HIV infection among patients presenting with indicator
      diseases. Of the remaining 56 patients, 29% were tested for HIV infection, with
      one new positive diagnosis. CONCLUSION: Longer hospital admission and infectious
      disease consult were associated with testing. Introduction of an HIV testing
      protocol based on the UK recommendations had no impact on testing rates. Given
      the high prevalence of HIV infection in these acute hospital settings, more
      intensive strategies are needed to facilitate testing.

PMID- 20040535
TI  - Movement and remodeling of the endoplasmic reticulum in nondividing cells of
      tobacco leaves.
AB  - Using a novel analytical tool, this study investigates the relative roles of
      actin, microtubules, myosin, and Golgi bodies on form and movement of the
      endoplasmic reticulum (ER) in tobacco (Nicotiana tabacum) leaf epidermal cells.
      Expression of a subset of truncated class XI myosins, which interfere with the
      activity of native class XI myosins, and drug-induced actin depolymerization
      produce a more persistent network of ER tubules and larger persistent cisternae.
      The treatments differentially affect two persistent size classes of cortical ER
      cisternae, those >0.3 microm(2) and those smaller, called punctae. The punctae
      are not Golgi, and ER remodeling occurs in the absence of Golgi bodies. The
      treatments diminish the mobile fraction of ER membrane proteins but not the
      diffusive flow of mobile membrane proteins. The results support a model whereby
      ER network remodeling is coupled to the directionality but not the magnitude of
      membrane surface flow, and the punctae are network nodes that act as foci of
      actin polymerization, regulating network remodeling through exploratory tubule
      growth and myosin-mediated shrinkage.

PMID- 20040536
TI  - Cell type-specific chromatin decondensation of a metabolic gene cluster in oats.
AB  - Transcription-related chromatin decondensation has been studied in mammals for
      clusters of structurally and/or functionally related genes that are coordinately
      regulated (e.g., the homeobox locus in mice and the major histocompatability
      complex locus in humans). Plant genes have generally been considered to be
      randomly distributed throughout the genome, although several examples of
      metabolic gene clusters for synthesis of plant defense compounds have recently
      been discovered. Clustering provides for genetic linkage of genes that together
      confer a selective advantage and may also facilitate coordinate regulation of
      gene expression by enabling localized changes in chromatin structure. Here, we
      use cytological methods to investigate components of a metabolic gene cluster for
      synthesis of developmentally regulated defense compounds (avenacins) in diploid
      oat (Avena strigosa). Our experiments reveal that expression of the avenacin gene
      cluster is associated with cell type-specific chromatin decondensation, providing
      new insights into regulation of gene clusters in plants. Importantly, chromatin
      decondensation could be visualized not only at the large-scale level but down to
      the single gene level. We further show that the avenacin and sterol pathways are
      likely to be inversely regulated at the level of transcription.

PMID- 20040537
TI  - DGAT1 and PDAT1 acyltransferases have overlapping functions in Arabidopsis
      triacylglycerol biosynthesis and are essential for normal pollen and seed
      development.
AB  - Triacylglycerol (TAG) biosynthesis is a principal metabolic pathway in most
      organisms, and TAG is the major form of carbon storage in many plant seeds. Acyl
      CoA:diacylglycerol acyltransferase 1 (DGAT1) is the only acyltransferase enzyme
      that has been confirmed to contribute to TAG biosynthesis in Arabidopsis thaliana
      seeds. However, dgat1 null mutants display only a 20 to 40% decrease in seed oil
      content. To determine whether other enzymes contribute to TAG synthesis,
      candidate genes were expressed in TAG-deficient yeast, candidate mutants were
      crossed with the dgat1-1 mutant, and target genes were suppressed by RNA
      interference (RNAi). An in vivo role for phospholipid:diacylglycerol
      acyltransferase 1 (PDAT1; At5g13640) in TAG synthesis was revealed in this study.
      After failing to obtain double homozygous plants from crossing dgat1-1 and pdat1
      2, further investigation showed that the dgat1-1 pdat1-2 double mutation resulted
      in sterile pollen that lacked visible oil bodies. RNAi silencing of PDAT1 in a
      dgat1-1 background or DGAT1 in pdat1-1 background resulted in 70 to 80% decreases
      in oil content per seed and in disruptions of embryo development. These results
      establish in vivo involvement of PDAT1 in TAG biosynthesis, rule out major
      contributions by other candidate enzymes, and indicate that PDAT1 and DGAT1 have
      overlapping functions that are essential for normal pollen and seed development
      of Arabidopsis.

PMID- 20040538
TI  - PIN auxin efflux carrier polarity is regulated by PINOID kinase-mediated
      recruitment into GNOM-independent trafficking in Arabidopsis.
AB  - The phytohormone auxin plays a major role in embryonic and postembryonic plant
      development. The temporal and spatial distribution of auxin largely depends on
      the subcellular polar localization of members of the PIN-FORMED (PIN) auxin
      efflux carrier family. The Ser/Thr protein kinase PINOID (PID) catalyzes PIN
      phosphorylation and crucially contributes to the regulation of apical-basal PIN
      polarity. The GTP exchange factor on ADP-ribosylation factors (ARF-GEF), GNOM
      preferentially mediates PIN recycling at the basal side of the cell. Interference
      with GNOM activity leads to dynamic PIN transcytosis between different sides of
      the cell. Our genetic, pharmacological, and cell biological approaches illustrate
      that PID and GNOM influence PIN polarity and plant development in an antagonistic
      manner and that the PID-dependent PIN phosphorylation results in GNOM-independent
      polar PIN targeting. The data suggest that PID and the protein phosphatase 2A not
      only regulate the static PIN polarity, but also act antagonistically on the rate
      of GNOM-dependent polar PIN transcytosis. We propose a model that includes PID
      dependent PIN phosphorylation at the plasma membrane and the subsequent sorting
      of PIN proteins to a GNOM-independent pathway for polarity alterations during
      developmental processes, such as lateral root formation and leaf vasculature
      development.

PMID- 20040539
TI  - Two types of meiotic crossovers coexist in maize.
AB  - We apply modeling approaches to investigate the distribution of late
      recombination nodules in maize (Zea mays). Such nodules indicate crossover
      positions along the synaptonemal complex. High-quality nodule data were analyzed
      using two different interference models: the "statistical" gamma model and the
      "mechanical" beam film model. For each chromosome, we exclude at a 98%
      significance level the hypothesis that a single pathway underlies the formation
      of all crossovers, pointing to the coexistence of two types of crossing-over in
      maize, as was previously demonstrated in other organisms. We estimate the
      proportion of crossovers coming from the noninterfering pathway to range from 6
      to 23% depending on the chromosome, with a cell average of approximately 15%. The
      mean number of noninterfering crossovers per chromosome is significantly
      correlated with the length of the synaptonemal complex. We also quantify the
      intensity of interference. Finally, we develop inference tools that allow one to
      tackle, without much loss of power, complex crossover interference models such as
      the beam film. The lack of a likelihood function in such models had prevented
      their use for parameter estimation. This advance will allow more realistic
      mechanisms of crossover formation to be modeled in the future.

PMID- 20040540
TI  - PLAZA: a comparative genomics resource to study gene and genome evolution in
      plants.
AB  - The number of sequenced genomes of representatives within the green lineage is
      rapidly increasing. Consequently, comparative sequence analysis has significantly
      altered our view on the complexity of genome organization, gene function, and
      regulatory pathways. To explore all this genome information, a centralized
      infrastructure is required where all data generated by different sequencing
      initiatives is integrated and combined with advanced methods for data mining.
      Here, we describe PLAZA, an online platform for plant comparative genomics
      (http://bioinformatics.psb.ugent.be/plaza/). This resource integrates structural
      and functional annotation of published plant genomes together with a large set of
      interactive tools to study gene function and gene and genome evolution.
      Precomputed data sets cover homologous gene families, multiple sequence
      alignments, phylogenetic trees, intraspecies whole-genome dot plots, and genomic
      colinearity between species. Through the integration of high confidence Gene
      Ontology annotations and tree-based orthology between related species, thousands
      of genes lacking any functional description are functionally annotated. Advanced
      query systems, as well as multiple interactive visualization tools, are available
      through a user-friendly and intuitive Web interface. In addition, detailed
      documentation and tutorials introduce the different tools, while the workbench
      provides an efficient means to analyze user-defined gene sets through PLAZA's
      interface. In conclusion, PLAZA provides a comprehensible and up-to-date research
      environment to aid researchers in the exploration of genome information within
      the green plant lineage.

PMID- 20040541
TI  - Auxin response in Arabidopsis under cold stress: underlying molecular mechanisms.
AB  - To understand the mechanistic basis of cold temperature stress and the role of
      the auxin response, we characterized root growth and gravity response of
      Arabidopsis thaliana after cold stress, finding that 8 to 12 h at 4 degrees C
      inhibited root growth and gravity response by approximately 50%. The auxin
      signaling mutants axr1 and tir1, which show a reduced gravity response, responded
      to cold treatment like the wild type, suggesting that cold stress affects auxin
      transport rather than auxin signaling. Consistently, expression analyses of an
      auxin-responsive marker, IAA2-GUS, and a direct transport assay confirmed that
      cold inhibits root basipetal (shootward) auxin transport. Microscopy of living
      cells revealed that trafficking of the auxin efflux carrier PIN2, which acts in
      basipetal auxin transport, was dramatically reduced by cold. The lateral
      relocalization of PIN3, which has been suggested to mediate the early phase of
      root gravity response, was also inhibited by cold stress. Additionally, cold
      differentially affected various protein trafficking pathways. Furthermore, the
      inhibition of protein trafficking by cold is independent of cellular actin
      organization and membrane fluidity. Taken together, these results suggest that
      the effect of cold stress on auxin is linked to the inhibition of intracellular
      trafficking of auxin efflux carriers.

PMID- 20040543
TI  - The cover. The virgin of Chancellor Rolin.

PMID- 20040544
TI  - A piece of my mind. The heart of the matter.

PMID- 20040542
TI  - Arabidopsis Tic62 and ferredoxin-NADP(H) oxidoreductase form light-regulated
      complexes that are integrated into the chloroplast redox poise.
AB  - Translocation of nuclear-encoded preproteins across the inner envelope of
      chloroplasts is catalyzed by the Tic translocon, consisting of Tic110, Tic40,
      Tic62, Tic55, Tic32, Tic20, and Tic22. Tic62 was proposed to act as a redox
      sensor of the complex because of its redox-dependent shuttling between envelope
      and stroma and its specific interaction with the photosynthetic protein
      ferredoxin-NADP(H) oxidoreductase (FNR). However, the nature of this close
      relationship so far remained enigmatic. A putative additional localization of
      Tic62 at the thylakoids mandated further studies examining how this feature might
      be involved in the respective redox sensing pathway and the interaction with its
      partner protein. Therefore, both the association with FNR and the physiological
      role of the third, thylakoid-bound pool of Tic62 were investigated in detail.
      Coexpression analysis indicates that Tic62 has similar expression patterns as
      genes involved in photosynthetic functions and protein turnover. At the
      thylakoids, Tic62 and FNR form high molecular weight complexes that are not
      involved in photosynthetic electron transfer but are dynamically regulated by
      light signals and the stromal pH. Structural analyses reveal that Tic62 binds to
      FNR in a novel binding mode for flavoproteins, with a major contribution from
      hydrophobic interactions. Moreover, in absence of Tic62, membrane binding and
      stability of FNR are drastically reduced. We conclude that Tic62 represents a
      major FNR interaction partner not only at the envelope and in the stroma, but
      also at the thylakoids of Arabidopsis thaliana and perhaps all flowering plants.
      Association with Tic62 stabilizes FNR and is involved in its dynamic and light
      dependent membrane tethering.

PMID- 20040545
TI  - Scientists target cocaine addiction.

PMID- 20040547
TI  - Adverse events and quadrivalent human papillomavirus recombinant vaccine.

PMID- 20040548
TI  - Efficacy data and HPV vaccination studies.

PMID- 20040549
TI  - Efficacy data and HPV vaccination studies.

PMID- 20040550
TI  - Marketing and the HPV vaccine.

PMID- 20040551
TI  - Marketing and the HPV vaccine.

PMID- 20040552
TI  - Indirect costs of structural interventions.

PMID- 20040553
TI  - Patient registries, predictive models, and optimal care.

PMID- 20040555
TI  - Association of telemedicine for remote monitoring of intensive care patients with
      mortality, complications, and length of stay.
AB  - CONTEXT: Telemedicine technology, which can enable intensivists to simultaneously
      monitor several intensive care units (ICUs) from an off-site location, is
      increasingly common, but there is little evidence to support its use. OBJECTIVE:
      To assess the association of remote monitoring of ICU patients (ICU telemedicine
      [tele-ICU]) with mortality, complications, and length of stay (LOS). DESIGN,
      SETTING, AND PATIENTS: Observational study conducted in 6 ICUs of 5 hospitals in
      a large US health care system to assess the use of tele-ICU. The study included
      2034 patients in the preintervention period (January 2003 to August 2005) and
      2108 patients in the postintervention period (July 2004 to July 2006). MAIN
      OUTCOME MEASURES: Hospital and ICU mortality, complications, and hospital and ICU
      survivors' LOS, with outcomes adjusted for severity of illness. RESULTS: Local
      physicians delegated full treatment authority to the tele-ICU for 655 patients
      (31.1%) and authority to intervene only in life-threatening events for the
      remainder. Observed hospital mortality rates were 12.0% (95% confidence interval
      [CI], 10.6% to 13.5%) in the preintervention period and 9.9% (95% CI, 8.6% to
      11.2%) in the postintervention period (preintervention to postintervention
      decrease, 2.1%; 95% CI, 0.2% to 4.1%; P = .03); observed ICU mortality rates were
      9.2% (95% CI, 8.0% to 10.5%) in the preintervention period and 7.8% (95% CI, 6.7%
      to 9.0%) in the postintervention period (preintervention to postintervention
      decrease, 1.4%; 95% CI, -0.3% to 3.2%; P = .12). After adjustment for severity of
      illness, there were no significant differences associated with the telemedicine
      intervention for hospital mortality (relative risk, 0.85; 95% CI, 0.71 to 1.03)
      or for ICU mortality (relative risk, 0.88; 95% CI, 0.71 to 1.08). There was a
      significant interaction between the tele-ICU intervention and severity of illness
      (P < .001), in which tele-ICU was associated with improved survival in sicker
      patients but with no improvement or worse outcomes in less sick patients. There
      were no significant differences between the preintervention and postintervention
      periods for hospital or ICU LOS. CONCLUSION: Remote monitoring of ICU patients
      was not associated with an overall improvement in mortality or LOS.

PMID- 20040554
TI  - Ginkgo biloba for preventing cognitive decline in older adults: a randomized
      trial.
AB  - CONTEXT: The herbal product Ginkgo biloba is taken frequently with the intention
      of improving cognitive health in aging. However, evidence from adequately powered
      clinical trials is lacking regarding its effect on long-term cognitive
      functioning. OBJECTIVE: To determine whether G. biloba slows the rates of global
      or domain-specific cognitive decline in older adults. DESIGN, SETTING, AND
      PARTICIPANTS: The Ginkgo Evaluation of Memory (GEM) study, a randomized, double
      blind, placebo-controlled clinical trial of 3069 community-dwelling participants
      aged 72 to 96 years, conducted in 6 academic medical centers in the United States
      between 2000 and 2008, with a median follow-up of 6.1 years. INTERVENTION: Twice
      daily dose of 120-mg extract of G. biloba (n = 1545) or identical-appearing
      placebo (n = 1524). MAIN OUTCOME MEASURES: Rates of change over time in the
      Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the
      Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains
      of memory, attention, visual-spatial construction, language, and executive
      functions, based on sums of z scores of individual tests. RESULTS: Annual rates
      of decline in z scores did not differ between G. biloba and placebo groups in any
      domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs
      0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95%
      CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118;
      95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI,
      0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95%
      CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline
      cognitive status (mild cognitive impairment), but there were no differences in
      rates of change between treatment groups (for 3MSE, P = .71; for ADAS-Cog, P =
      .97). There was no significant effect modification of treatment on rate of
      decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive
      impairment (P > .05). CONCLUSION: Compared with placebo, the use of G. biloba,
      120 mg twice daily, did not result in less cognitive decline in older adults with
      normal cognition or with mild cognitive impairment. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00010803.

PMID- 20040556
TI  - Strength of study evidence examined by the FDA in premarket approval of
      cardiovascular devices.
AB  - CONTEXT: Medical devices are common in clinical practice and have important
      effects on morbidity and mortality, yet there has not been a systematic
      examination of evidence used by the US Food and Drug Administration (FDA) for
      device approval. OBJECTIVES: To study premarket approval (PMA)--the most
      stringent FDA review process--of cardiovascular devices and to characterize the
      type and strength of evidence on which it is based. DATA SOURCES AND STUDY
      SELECTION: Systematic review of 78 summaries of safety and effectiveness data for
      78 PMAs for high risk cardiovascular devices that received PMA between January
      2000 and December 2007 [corrected]. DATA EXTRACTION: Examination of the
      methodological characteristics considered essential to minimize confounding and
      bias, as well as the primary end points of the 123 studies supporting the PMAs.
      RESULTS: Thirty-three of 123 studies (27%) used to support recent FDA approval of
      cardiovascular devices were randomized and 17 of 123 (14%) were blinded. Fifty
      one of 78 PMAs (65%) were based on a single study. One hundred eleven of 213
      primary end points (52%) were compared with controls and 34 of 111 controls (31%)
      were retrospective. One hundred eighty-seven of 213 primary end points (88%) were
      surrogate measures and 122 of 157 (78%) had a discrepancy between the number of
      patients enrolled in the study and the number analyzed. CONCLUSION: Premarket
      approval of cardiovascular devices by the FDA is often based on studies that lack
      adequate strength and may be prone to bias.

PMID- 20040557
TI  - Medical care for the final years of life: "When you're 83, it's not going to be
      20 years".
AB  - The case of an 83-year-old man who has had a fall-related injury and continues to
      be the sole caregiver for his wife who has dementia exemplifies a common
      situation that clinicians face--planning for the final years of an elderly
      individual's life. To appropriately focus on the patient's most pressing issues,
      the approach should begin with an assessment of life expectancy and incorporation
      of evidence-based care whenever possible. Short-term issues are focused on
      efforts to restore the patient to his previous state of health. Mid-range issues
      address providing preventive care, identifying geriatric syndromes, and helping
      him cope with the psychosocial needs of being a caregiver. Long-term issues
      relate to planning for his eventual decline and meeting his goals for the end of
      life. Unfortunately, the workload and inefficiencies of primary care practice
      present barriers to providing optimal care for older patients. Systematic
      approaches, including team care, are needed to adequately manage chronic diseases
      and coordinate care.

PMID- 20040558
TI  - Translating intergenerational research on depression into clinical practice.

PMID- 20040559
TI  - Strengthening institutional review board review of highly innovative
      interventions in clinical trials.

PMID- 20040560
TI  - Improving the delivery of preventive services to Medicare beneficiaries.

PMID- 20040561
TI  - Policy for an aging society: a review of systems.

PMID- 20040562
TI  - Clinical care in the aging century--announcing "Care of the aging patient: from
      evidence to action".

PMID- 20040563
TI  - Evaluating telemedicine in the ICU.

PMID- 20040564
TI  - JAMA patient page. Preventive care for older adults.

PMID- 20040565
TI  - More on high street mole checks.

PMID- 20040566
TI  - Management of medication overuse headache.
AB  - Headache is one of the most frequent reasons for medical consultation in both
      general practice and specialist neurology clinics.1 Prescribed and over-the
      counter medications are taken to alleviate headaches, but may be used
      incorrectly.2 In particular, use of some drugs both frequently and regularly can
      have a paradoxical effect, causing headaches rather than relieving them, and
      leading to medication overuse headache (MOH).3 Such overuse is a common cause of
      frequent headache. Here we review MOH and its management.

PMID- 20040567
TI  - Cognitive behavioural therapy for schizophrenia.
AB  - Around 0.7% of the population have schizophrenia. This serious psychotic disorder
      affects psychological and social functioning, and diagnosis can lead to stigma.
      Pharmacological interventions are a key element in management, but are sometimes
      ineffective and nearly half of patients do not adhere to drug treatment.
      Cognitive behavioural therapy (CBT) is now being used as adjunctive treatment in
      the management of patients with schizophrenia. Here we consider this approach.

PMID- 20040568
TI  - Tocilizumab for rheumatoid arthritis.
AB  - Tocilizumab (RoActemra-Roche) is a new biological agent available in the UK for
      the treatment of adults with rheumatoid arthritis.1 Unlike currently available
      biological agents, the drug targets the pro-inflammatory cytokine interleukin-6
      (IL-6). Here, we consider the place of tocilizumab in rheumatoid arthritis and
      whether it offers any advantages over other biological agents.

PMID- 20040569
TI  - Noninvasive brain stimulation with low-intensity electrical currents: putative
      mechanisms of action for direct and alternating current stimulation.
AB  - Transcranial stimulation with weak direct current (DC) has been valuable in
      exploring the effect of cortical modulation on various neural networks. Less
      attention has been given, however, to cranial stimulation with low-intensity
      alternating current (AC). Reviewing and discussing these methods simultaneously
      with special attention to what is known about their mechanisms of action may
      provide new insights for the field of noninvasive brain stimulation. Direct
      current appears to modulate spontaneous neuronal activity in a polarity-dependent
      fashion with site-specific effects that are perpetuated throughout the brain via
      networks of interneuronal circuits, inducing significant effects on high-order
      cortical processes implicated in decision making, language, memory, sensory
      perception, and pain. AC stimulation has also been associated with a significant
      behavioral and clinical impact, but the mechanism of AC stimulation has been
      underinvestigated in comparison with DC stimulation. Even so, preliminary studies
      show that although AC stimulation has only modest effects on cortical
      excitability, it has been shown to induce synchronous changes in brain activity
      as measured by EEG activity. Thus, cranial AC stimulation may render its effects
      not by polarizing brain tissue, but rather via rhythmic stimulation that
      synchronizes and enhances the efficacy of endogenous neurophysiologic activity.
      Alternatively, secondary nonspecific central and peripheral effects may explain
      the clinical outcomes of DC or AC stimulation. Here the authors review what is
      known about DC and AC stimulation, and they discuss features that remain to be
      investigated.

PMID- 20040570
TI  - A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor.
AB  - Chromatin reorganization is essential for transcriptional control by sequence
      specific transcription factors. However, the molecular link between
      transcriptional control and chromatin reconfiguration remains unclear. By
      colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced
      puff in the salivary gland, Drosophila DEK (dDEK) was genetically identified as a
      coactivator of EcR in both insect cells and intact flies. Biochemical
      purification and characterization of the complexes containing fly and human DEKs
      revealed that DEKs serve as histone chaperones via phosphorylation by forming
      complexes with casein kinase 2. Consistent with the preferential association of
      the DEK complex with histones enriched in active epigenetic marks, dDEK
      facilitated H3.3 assembly during puff formation. In some human myeloid leukemia
      patients, DEK was fused to CAN by chromosomal translocation. This mutation
      significantly reduced formation of the DEK complex, which is required for histone
      chaperone activity. Thus, the present study suggests that at least one histone
      chaperone can be categorized as a type of transcriptional coactivator for nuclear
      receptors.

PMID- 20040571
TI  - Regulation of the p53 transcriptional response by structurally diverse core
      promoters.
AB  - p53 target promoters are structurally diverse and display pronounced differences
      in RNA polymerase II (RNAP II) occupancy even in unstressed cells, with higher
      levels observed on cell cycle arrest genes (p21) compared with apoptotic genes
      (Fas/APO1). This occupancy correlates well with their ability to undergo rapid or
      delayed stress induction. To understand the basis for such distinct temporal
      assembly of transcription complexes, we examined the role of core promoter
      structures in this process. We find that the p21 core promoter directs rapid,
      TATA box-dependent assembly of RNAP II preinitiation complexes (PICs), but
      permits few rounds of RNAP II reinitiation. In contrast, PIC formation at the
      Fas/APO1 core promoter is very inefficient but supports multiple rounds of
      transcription. We define a downstream element within the Fas/APO1 core promoter
      that is essential for its activation, and identify nuclear transcription factor Y
      (NF-Y) as its binding partner. NF-Y acts as a bifunctional transcription factor
      that regulates basal expression of Fas/APO1 in vivo. Thus, two critical
      parameters of the stress-induced p53 transcriptional response are the kinetics of
      gene induction and duration of expression through frequent reinitiation. These
      features are intrinsic, DNA-encoded properties of diverse core promoters that may
      be fundamental to anticipatory programming of p53 response genes upon stress.

PMID- 20040572
TI  - Optimization of the hybridization-based method for purification of thermostable
      tRNAs in the presence of tetraalkylammonium salts.
AB  - We found that both tetramethylammonium chloride (TMA-Cl) and tetra-ethylammonium
      chloride (TEA-Cl), which are used as monovalent cations for northern
      hybridization, drastically destabilized the tertiary structures of tRNAs and
      enhanced the formation of tRNA*oligoDNA hybrids. These effects are of great
      advantage for the hybridization-based method for purification of specific tRNAs
      from unfractionated tRNA mixtures through the use of an immobilized oligoDNA
      complementary to the target tRNA. Replacement of NaCl by TMA-Cl or TEA-Cl in the
      hybridization buffer greatly improved the recovery of a specific tRNA, even from
      unfractionated tRNAs derived from a thermophile. Since TEA-Cl destabilized tRNAs
      more strongly than TMA-Cl, it was necessary to lower the hybridization
      temperature at the sacrifice of the purity of the recovered tRNA when using TEA
      Cl. Therefore, we propose two alternative protocols, depending on the desired
      properties of the tRNA to be purified. When the total recovery of the tRNA is
      important, hybridization should be carried out in the presence of TEA-Cl.
      However, if the purity of the recovered tRNA is important, TMA-Cl should be used
      for the hybridization. In principle, this procedure for tRNA purification should
      be applicable to any small-size RNA whose gene sequence is already known.

PMID- 20040573
TI  - A novel function for the Mre11-Rad50-Xrs2 complex in base excision repair.
AB  - The Mre11/Rad50/Xrs2 (MRX) complex in Saccharomyces cerevisiae has well
      characterized functions in DNA double-strand break processing, checkpoint
      activation, telomere length maintenance and meiosis. In this study, we
      demonstrate an involvement of the complex in the base excision repair (BER)
      pathway. We studied the repair of methyl-methanesulfonate-induced heat-labile
      sites in chromosomal DNA in vivo and the in vitro BER capacity for the repair of
      uracil- and 8-oxoG-containing oligonucleotides in MRX-deficient cells. Both
      approaches show a clear BER deficiency for the xrs2 mutant as compared to
      wildtype cells. The in vitro analyses revealed that both subpathways, long-patch
      and short-patch BER, are affected and that all components of the MRX complex are
      similarly important for the new function in BER. The investigation of the
      epistatic relationship of XRS2 to other BER genes suggests a role of the MRX
      complex downstream of the AP-lyases Ntg1 and Ntg2. Analysis of individual steps
      in BER showed that base recognition and strand incision are not affected by the
      MRX complex. Reduced gap-filling activity and the missing effect of aphidicoline
      treatment, an inhibitor for polymerases, on the BER efficiency indicate an
      involvement of the MRX complex in providing efficient polymerase activity.

PMID- 20040574
TI  - The human Holliday junction resolvase GEN1 rescues the meiotic phenotype of a
      Schizosaccharomyces pombe mus81 mutant.
AB  - A key step in meiotic recombination involves the nucleolytic resolution of
      Holliday junctions to generate crossovers. Although the enzyme that performs this
      function in human cells is presently unknown, recent studies led to the
      identification of the XPG-family endonuclease GEN1 that promotes Holliday
      junction resolution in vitro, suggesting that it may perform a related function
      in vivo. Here, we show that ectopic expression of GEN1 in fission yeast
      mus81Delta strains results in Holliday junction resolution and crossover
      formation during meiosis.

PMID- 20040575
TI  - Linear plasmid vector for cloning of repetitive or unstable sequences in
      Escherichia coli.
AB  - Despite recent advances in sequencing, complete finishing of large genomes and
      analysis of novel proteins they encode typically require cloning of specific
      regions. However, many of these fragments are extremely difficult to clone in
      current vectors. Superhelical stress in circular plasmids can generate secondary
      structures that are substrates for deletion, particularly in regions that contain
      numerous tandem or inverted repeats. Common vectors also induce transcription and
      translation of inserted fragments, which can select against recombinant clones
      containing open reading frames or repetitive DNA. Conversely, transcription from
      cloned promoters can interfere with plasmid stability. We have therefore
      developed a novel Escherichia coli cloning vector (termed 'pJAZZ' vector) that is
      maintained as a linear plasmid. Further, it contains transcriptional terminators
      on both sides of the cloning site to minimize transcriptional interference
      between vector and insert. We show that this vector stably maintains a variety of
      inserts that were unclonable in conventional plasmids. These targets include
      short nucleotide repeats, such as those of the expanded Fragile X locus, and
      large AT-rich inserts, such as 20-kb segments of genomic DNA from Pneumocystis,
      Plasmodium, Oxytricha or Tetrahymena. The pJAZZ vector shows decreased size bias
      in cloning, allowing more uniform representation of larger fragments in
      libraries.

PMID- 20040576
TI  - Rearrangement of the RNA polymerase subunit H and the lower jaw in archaeal
      elongation complexes.
AB  - The lower jaws of archaeal RNA polymerase and eukaryotic RNA polymerase II
      include orthologous subunits H and Rpb5, respectively. The tertiary structure of
      H is very similar to the structure of the C-terminal domain of Rpb5, and both
      subunits are proximal to downstream DNA in pre-initiation complexes. Analyses of
      reconstituted euryarchaeal polymerase lacking subunit H revealed that H is
      important for open complex formation and initial transcription. Eukaryotic Rpb5
      rescues activity of the DeltaH enzyme indicating a strong conservation of
      function for this subunit from archaea to eukaryotes. Photochemical cross-linking
      in elongation complexes revealed a striking structural rearrangement of RNA
      polymerase, bringing subunit H near the transcribed DNA strand one helical turn
      downstream of the active center, in contrast to the positioning observed in
      preinitiation complexes. The rearrangement of subunits H and A'' suggest a major
      conformational change in the archaeal RNAP lower jaw upon formation of the
      elongation complex.

PMID- 20040578
TI  - Clarithromycin inhibits type a seasonal influenza virus infection in human airway
      epithelial cells.
AB  - Human influenza viruses attach to sialic acid with an alpha2,6linkage
      (SAalpha2,6Gal) on the airway epithelial cells, and the entry of the viruses into
      the cells and uncoating of the viruses require low pH of endosomes. Bafilomycin
      A(1), a macrolide antibiotic and a specific inhibitor of vacuolar H(+)-ATPase,
      inhibits growth of type A and type B human influenza viruses in Madin-Darby
      canine kidney cells. However, the inhibitory effects of clinically used macrolide
      antibiotics on influenza virus infection in human airways have not been studied.
      To examine the effects of clarithromycin on seasonal human influenza virus
      infection, cultured human tracheal epithelial cells were infected with type A
      influenza virus (H3N2). Influenza virus infection increased viral titers and the
      content of cytokines, including interleukin (IL)-1beta and IL-6, in supernatant
      fluids, and viral RNA in the cells. Clarithromycin reduced viral titers and the
      content of cytokines in supernatant fluids, viral RNA in the cells, and the
      susceptibility to virus infection. Clarithromycin reduced the expression of
      SAalpha2,6Gal, a receptor for human influenza virus, on the mucosal surface of
      human tracheae, and the number and fluorescence intensity of acidic endosomes in
      the cells from which viral ribonucleoproteins enter into the cytoplasm.
      Furthermore, clarithromycin reduced nuclear factor-kappaB (NF-kappaB) proteins,
      including p50 and p65, in the nuclear extracts. These results suggest that
      clarithromycin may inhibit seasonal human influenza virus infection by reducing
      SAalpha2,6Gal partly through the inhibition of NF-kappaB, and increasing pH in
      endosomes in airway epithelial cells. Clarithromycin may modulate airway
      inflammation in influenza virus infection.

PMID- 20040577
TI  - Crystal structure of Tpa1 from Saccharomyces cerevisiae, a component of the
      messenger ribonucleoprotein complex.
AB  - Tpa1 (for termination and polyadenylation) from Saccharomyces cerevisiae is a
      component of a messenger ribonucleoprotein (mRNP) complex at the 3' untranslated
      region of mRNAs. It comprises an N-terminal Fe(II)- and 2-oxoglutarate (2OG)
      dependent dioxygenase domain and a C-terminal domain. The N-terminal dioxygenase
      domain of a homologous Ofd1 protein from Schizosaccharomyces pombe was proposed
      to serve as an oxygen sensor that regulates the activity of the C-terminal
      degradation domain. Members of the Tpa1 family are also present in higher
      eukaryotes including humans. Here we report the crystal structure of S.
      cerevisiae Tpa1 as a representative member of the Tpa1 family. Structures have
      been determined as a binary complex with Fe(III) and as a ternary complex with
      Fe(III) and 2OG. The structures reveal that both domains of Tpa1 have the double
      stranded beta-helix fold and are similar to prolyl 4-hydroxylases. However, the
      binding of Fe(III) and 2OG is observed in the N-terminal domain only. We also
      show that Tpa1 binds to poly(rA), suggesting its direct interaction with mRNA in
      the mRNP complex. The structural and functional data reported in this study
      support a role of the Tpa1 family as a hydroxylase in the mRNP complex and as an
      oxygen sensor.

PMID- 20040579
TI  - Twenty-four-hour exposure to altered blood flow modifies endothelial Ca2+
      activated K+ channels in rat mesenteric arteries.
AB  - We tested the hypothesis that changes in arterial blood flow modify the function
      of endothelial Ca2+-activated K+ channels [calcium-activated K+ channel (K(Ca)),
      small-conductance calcium-activated K+ channel (SK3), and intermediate calcium
      activated K+ channel (IK1)] before arterial structural remodeling. In rats,
      mesenteric arteries were exposed to increased [+90%, high flow (HF)] or reduced
      blood flow [-90%, low flow (LF)] and analyzed 24 h later. There were no
      detectable changes in arterial structure or in expression level of endothelial
      nitric-oxide synthase, SK3, or IK1. Arterial relaxing responses to acetylcholine
      and 3-oxime-6,7-dichlore-1H-indole-2,3-dione (NS309; activator of SK3 and IK1)
      were measured in the absence and presence of endothelium, NO, and prostanoid
      blockers, and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-metheno
      7H-dibenzo [b,n] [1,5,12,16]tetraazacyclotricosine-5,13-diium dibromide (UCL
      1684; inhibitor of SK3) or 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM
      34; inhibitor of IK1). In LF arteries, endothelium-dependent relaxation was
      markedly reduced, due to a reduction in the endothelium-derived hyperpolarizing
      factor (EDHF) response. In HF arteries, the balance between the NO/prostanoid
      versus EDHF response was unaltered. However, the contribution of IK1 to the EDHF
      response was enhanced, as indicated by a larger effect of TRAM-34 and a larger
      residual NS309-induced relaxation in the presence of UCL 1684. Reduction of blood
      flow selectively blunts EDHF relaxation in resistance arteries through inhibition
      of the function of K(Ca) channels. An increase in blood flow leads to a more
      prominent role of IK1 channels in this relaxation.

PMID- 20040580
TI  - Expression, localization, and pharmacological role of Kv7 potassium channels in
      skeletal muscle proliferation, differentiation, and survival after myotoxic
      insults.
AB  - Changes in the expression of potassium channels regulate skeletal muscle
      development. The purpose of this study was to investigate the expression profile
      and pharmacological role of K(v)7 voltage-gated potassium channels in skeletal
      muscle differentiation, proliferation, and survival after myotoxic insults.
      Transcripts for all K(v)7 genes (K(v)7.1-K(v)7.5) were detected by polymerase
      chain reaction (PCR) and/or real-time PCR in murine C(2)C(12) myoblasts; K(v)7.1,
      K(v)7.3, and K(v)7.4 transcripts were up-regulated after myotube formation.
      Western blot experiments confirmed K(v)7.2, K(v)7.3, and K(v)7.4 subunit
      expression, and the up-regulation of K(v)7.3 and K(v)7.4 subunits during in vitro
      differentiation. In adult skeletal muscles from mice and humans, K(v)7.2 and
      K(v)7.3 immunoreactivity was mainly localized at the level of intracellular
      striations positioned between ankyrinG-positive triads, whereas that of K(v)7.4
      subunits was largely restricted to the sarcolemmal membrane. In C(2)C(12) cells,
      retigabine (10 microM), a specific activator of neuronally expressed K(v)7.2 to
      K(v)7.5 subunits, reduced proliferation, accelerated myogenin expression, and
      inhibited the myotoxic effect of mevastatin (IC(50) approximately 7 microM); all
      these effects of retigabine were prevented by the K(v)7 channel blocker 10,10
      bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991) (10 muM). These data
      collectively highlight neural K(v)7 channels as significant pharmacological
      targets to regulate skeletal muscle proliferation, differentiation, and myotoxic
      effects of drugs.

PMID- 20040581
TI  - Cross-species comparison of the metabolism and excretion of zoniporide:
      contribution of aldehyde oxidase to interspecies differences.
AB  - Excretion and metabolism of zoniporide were investigated in humans after
      intravenous infusion of [(14)C]zoniporide at an 80-mg dose. Bile was the primary
      route of excretion because 57% of dose was recovered in the feces after
      intravenous infusion. Zoniporide was primarily cleared via metabolism in humans.
      2-Oxozoniporide (M1) was the major excretory and circulating metabolite in humans
      and was catalyzed by aldehyde oxidase (K(m) of 3.4 microM and V(max) of 74
      pmol/min/mg protein). Metabolites M2 (17% of the dose) and M3 (6.4% of
      circulating radioactivity), in which the guanidine moiety was hydrolyzed to a
      carboxylic acid, were also detected in human feces and plasma, respectively,
      suggesting that hydrolysis was another route of metabolism of zoniporide in
      humans. The metabolism and excretion of [(14)C]zoniporide in rats and dogs were
      also evaluated. As in humans, bile was the primary route of excretion of the
      radiolabeled material in both species, and metabolism was the primary route of
      clearance. A comparison of plasma metabolites showed that for M3, rats had a
      higher concentration than human or dog. M1 was absent in dog and present in human
      and rat plasma at comparable levels, whereas comparison of excreta showed that
      the total body burden of M1 was greater in rat than that in human. No further
      evaluation of M2 was considered because it was detected only in the human fecal
      extracts. Hence, no further toxicological evaluation of the three human
      metabolites was undertaken.

PMID- 20040582
TI  - Polychlorinated biphenyl-mediated decrease in serum thyroxine level in rodents.
AB  - Effects of Kanechlor-500 (KC500), a commercial polychlorinated biphenyl mixture,
      on the levels of serum thyroid hormones such as total thyroxine (T(4)) and
      triiodothyronine were examined in male mice, hamsters, rats, and guinea pigs.
      Four days after a single intraperitoneal injection of KC500, significant
      decreases in the levels of the serum total T(4) and free T(4) occurred in all the
      animals examined, whereas a significant decrease in the level of serum
      triiodothyronine was observed only in guinea pigs among the animals examined. In
      addition, no significant change in the level of serum thyroid-stimulating hormone
      was observed in any of the rodents examined. A significant increase in the
      activity of hepatic T(4)-UDP-glucuronosyltransferase after the KC500
      administration occurred only in guinea pigs, whereas the increase in the amount
      of biliary [(125)I]T(4) glucuronide after an intravenous injection of
      [(125)I]T(4) to the KC500-pretreated animals occurred only in rats. On the other
      hand, in all the rodents examined, KC500-pretreatment promoted the clearance of
      [(125)I]T(4) from the serum and led to a significant increase in the steady-state
      distribution volumes of [(125)I]T(4). Likewise, its pretreatment raised the
      concentration ratio (K(p) value) of the liver to serum and the liver distribution
      of [(125)I]T(4) in all the rodents tested. The present findings indicate that for
      the first time the KC500-mediated decrease in the serum T(4) level in mice,
      hamsters, rats and guinea pigs occurs mainly through an increase in the
      accumulation level of T(4) in the liver.

PMID- 20040583
TI  - High-throughput sequencing of retrotransposon integration provides a saturated
      profile of target activity in Schizosaccharomyces pombe.
AB  - The biological impact of transposons on the physiology of the host depends
      greatly on the frequency and position of integration. Previous studies of Tf1, a
      long terminal repeat retrotransposon in Schizosaccharomyces pombe, showed that
      integration occurs at the promoters of RNA polymerase II (Pol II) transcribed
      genes. To determine whether specific promoters are preferred targets of
      integration, we sequenced large numbers of insertions using high-throughput
      pyrosequencing. In four independent experiments we identified a total of 73,125
      independent integration events. These data provided strong support for the
      conclusion that Pol II promoters are the targets of Tf1 integration. The size and
      number of the integration experiments resulted in reproducible measures of
      integration for each intergenic region and ORF in the S. pombe genome. The
      reproducibility of the integration activity from experiment to experiment
      demonstrates that we have saturated the full set of insertion sites that are
      actively targeted by Tf1. We found Tf1 integration was highly biased in favor of
      a specific set of Pol II promoters. The overwhelming majority (76%) of the
      insertions were distributed in intergenic sequences that contained 31% of the
      promoters of S. pombe. Interestingly, there was no correlation between the amount
      of integration at these promoters and their level of transcription. Instead, we
      found Tf1 had a strong preference for promoters that are induced by conditions of
      stress. This targeting of stress response genes coupled with the ability of Tf1
      to regulate the expression of adjacent genes suggests Tf1 may improve the
      survival of S. pombe when cells are exposed to environmental stress.

PMID- 20040584
TI  - Function and expression pattern of the alpha subunit of the heterotrimeric G
      protein in rice.
AB  - The d1 mutant, which is deficient for the heterotrimeric G-protein alpha subunit
      (Galpha) gene of rice, shows dwarfism and sets small round seeds. To determine
      whether dwarfism in d1 is due to a reduction in cell number or to shortened cell
      length, the cell number of the leaf sheath, the internode, the root and the lemma
      was compared between Nipponbare, a wild-type rice and d1-5, a d1 allele derived
      from Nipponbare. Our results indicate that the cell number was reduced in all
      organs analyzed in d1-5. In addition, cell enlargement was found in roots and
      lemma of d1-5, although the organ length in d1-5 was shorter than that of wild
      type rice. These results suggest that rice Galpha participates in cell
      proliferation in rice. Western blot analyses using anti-Galpha antibody and RT
      PCR analyses indicate that Galpha is mostly expressed in the developing organs.
      Galpha promoter activity studies using the GUS reporter gene confirmed that the
      expression of Galpha was highest in developing organs. We conclude that rice
      Galpha participates in the regulation of cell number in a developmental stage
      dependent manner.

PMID- 20040585
TI  - The bHLH transcription factor SPATULA controls final leaf size in Arabidopsis
      thaliana.
AB  - Leaves possess intrinsic information about their final size, but the
      developmental mechanisms setting the limits of growth are not well characterized.
      By screening enhancer trap lines that show a specific expression pattern in leaf
      primordia, we isolated one line, 576. This line contains a T-DNA insertion
      upstream of the basic helix-loop-helix (bHLH) transcription factor SPATULA (SPT)
      gene, and shows expression in the basal region of young leaves, where cell
      proliferation is active. An spt loss-of-function mutation increased leaf size and
      total cell number within a leaf, while SPT overexpression decreased leaf size and
      total cell number within a leaf. Although spt mutations did not affect cell size,
      SPT overexpression decreased the cell size in fully expanded leaves. Genetic
      analysis suggested that SPT acts independently from another set of cell
      proliferation-dependent organ size regulators ANGUSTIFOLIA3 (AN3) and GROWTH
      REGULATING FACTOR5 (AtGRF5). Detailed analysis of spt leaf development showed
      that the spt mutation enlarged the size of the meristematic region in leaf
      primordia, while overexpression of AtGRF5 promoted cell proliferation without
      affecting the enlargement of the meristematic region. These results suggest that
      SPT functions as a repressor of leaf growth and that meristematic region size in
      young leaf primordia, in terms of proliferative cell number within leaf
      primordia, is another target of leaf size determination, which previously had not
      been identified.

PMID- 20040586
TI  - The HSP terminator of Arabidopsis thaliana increases gene expression in plant
      cells.
AB  - To express a foreign gene in plants effectively, a good expression system is
      required. Here we describe the identification of a transcriptional terminator
      that supports increased levels of expression. The terminators of several
      Arabidopsis genes were examined in transfected Arabidopsis T87 protoplasts. The
      heat shock protein 18.2 (HSP) terminator was the most effective in supporting
      increased levels of expression. The HSP terminator increases mRNA levels of both
      transiently and stably expressed transgenes approximately 2-fold more than the
      NOS (nopaline synthase) terminator. When combined with the HSP terminator, a
      translational enhancer increased gene expression levels approximately 60- to 100
      fold in transgenic plants.

PMID- 20040587
TI  - Mixtures of regression models for time course gene expression data: evaluation of
      initialization and random effects.
AB  - SUMMARY: Finite mixture models are routinely applied to time course microarray
      data. Due to the complexity and size of this type of data, the choice of good
      starting values plays an important role. So far initialization strategies have
      only been investigated for data from a mixture of multivariate normal
      distributions. In this work several initialization procedures are evaluated for
      mixtures of regression models with and without random effects in an extensive
      simulation study on different artificial datasets. Finally, these procedures are
      also applied to a real dataset from Escherichia coli. AVAILABILITY: The latest
      release versions of R packages flexmix, gcExplorer and kernlab are always
      available from CRAN (http://cran.r-project.org/). SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 20040588
TI  - GWAF: an R package for genome-wide association analyses with family data.
AB  - SUMMARY: GWAF, Genome-Wide Association analyses with Family, is an R package
      designed for GWAF. It implements association tests between a batch of genotyped
      or imputed single nucleotide polymorphisms (SNPs) and a binary or continuous
      trait with user specified genetic model, and generates informative results from
      the analyses. In addition, GWAF provides functions to visualize results. We
      evaluated GWAF using a simulated continuous trait and a binary trait dichotomized
      from the simulated continuous trait with real genotype data from the Framingham
      Heart Study's SNP Health Association Resource project.

PMID- 20040589
TI  - Evidence for bacterial origin of heat shock RNA-1.
AB  - The heat shock RNA-1 (HSR1) is a noncoding RNA (ncRNA) reported to be involved in
      mammalian heat shock response. HSR1 was shown to significantly stimulate the heat
      shock factor 1 (HSF1) trimerization and DNA binding. The hamster HSR1 sequence
      was reported to consist of 604 nucleotides (nt) plus a poly(A) tail and to have
      only a 4-nt difference with the human HSR1. In this study, we present highly
      convincing evidence for bacterial origin of the HSR1. No HSR1 sequence was found
      by exhaustive sequence similarity searches of the publicly available eukaryotic
      nucleotide sequence databases at the NCBI, including the expressed sequence tags,
      genome survey sequences, and high-throughput genomic sequences divisions of
      GenBank, as well as the Trace Archive database of whole genome shotgun sequences,
      and genome assemblies. Instead, a putative open reading frame (ORF) of HSR1
      revealed strong similarity to the amino-terminal region of bacterial chloride
      channel proteins. Furthermore, the 5' flanking region of the putative HSR1 ORF
      showed similarity to the 5' upstream regions of the bacterial protein genes. We
      propose that the HSR1 was derived from a bacterial genome fragment either by
      horizontal gene transfer or by bacterial infection of the cells. The most
      probable source organism of the HSR1 is a species belonging to the order
      Burkholderiales.

PMID- 20040590
TI  - Preferential translation of Hsp83 in Leishmania requires a thermosensitive
      polypyrimidine-rich element in the 3' UTR and involves scanning of the 5' UTR.
AB  - Heat shock proteins (HSPs) provide a useful system for studying developmental
      patterns in the digenetic Leishmania parasites, since their expression is induced
      in the mammalian life form. Translation regulation plays a key role in control of
      protein coding genes in trypanosomatids, and is directed exclusively by elements
      in the 3' untranslated region (UTR). Using sequential deletions of the Leishmania
      Hsp83 3' UTR (888 nucleotides [nt]), we mapped a region of 150 nt that was
      required, but not sufficient for preferential translation of a reporter gene at
      mammalian-like temperatures, suggesting that changes in RNA structure could be
      involved. An advanced bioinformatics package for prediction of RNA folding
      (UNAfold) marked the regulatory region on a highly probable structural arm that
      includes a polypyrimidine tract (PPT). Mutagenesis of this PPT abrogated
      completely preferential translation of the fused reporter gene. Furthermore,
      temperature elevation caused the regulatory region to melt more extensively than
      the same region that lacked the PPT. We propose that at elevated temperatures the
      regulatory element in the 3' UTR is more accessible to mediators that promote its
      interaction with the basal translation components at the 5' end during mRNA
      circularization. Translation initiation of Hsp83 at all temperatures appears to
      proceed via scanning of the 5' UTR, since a hairpin structure abolishes
      expression of a fused reporter gene.

PMID- 20040591
TI  - The nuclear experience of CPEB: implications for RNA processing and translational
      control.
AB  - CPEB is a sequence-specific RNA binding protein that promotes polyadenylation
      induced translation in early development, during cell cycle progression and
      cellular senescence, and following neuronal synapse stimulation. It controls
      polyadenylation and translation through other interacting molecules, most notably
      the poly(A) polymerase Gld2, the deadenylating enzyme PARN, and the eIF4E-binding
      protein Maskin. Here, we report that CPEB shuttles between the nucleus and
      cytoplasm and that its export occurs via the CRM1-dependent pathway. In the
      nucleus of Xenopus oocytes, CPEB associates with lampbrush chromosomes and
      several proteins involved in nuclear RNA processing. CPEB also interacts with
      Maskin in the nucleus as well as with CPE-containing mRNAs. Although the CPE does
      not regulate mRNA export, it influences the degree to which mRNAs are
      translationally repressed in the cytoplasm. Moreover, CPEB directly or indirectly
      mediates the alternative splicing of at least one pre-mRNA in mouse embryo
      fibroblasts as well as certain mouse tissues. We propose that CPEB, together with
      Maskin, binds mRNA in the nucleus to ensure tight translational repression upon
      export to the cytoplasm. In addition, we propose that nuclear CPEB regulates
      specific pre-mRNA alternative splicing.

PMID- 20040592
TI  - Neuron-type specific regulation of a 3'UTR through redundant and combinatorially
      acting cis-regulatory elements.
AB  - 3' Untranslated region (UTR)-dependent post-transcriptional regulation has
      emerged as a critical mechanism of controlling gene expression in various
      physiological contexts, including cellular differentiation events. Here, we
      examine the regulation of the 3'UTR of the die-1 transcription factor in a single
      neuron of the nematode C. elegans. This 3'UTR shows the intriguing feature of
      being differentially regulated across the animal's left/right axis. In the left
      gustatory neuron, ASEL, in which DIE-1 protein is normally expressed in adult
      animals, the 3'UTR confers no regulatory information, while in the right
      gustatory neuron, ASER, where DIE-1 is normally not expressed, this 3'UTR confers
      negative regulatory information. Here, we systematically analyze the cis
      regulatory architecture of the die-1 3'UTR using a transgenic, in vivo assay
      system. Through extensive mutagenesis and sequence insertions into heterologous
      3'UTR contexts, we describe three 25-base-pair (bp) sequence elements that are
      both required and sufficient to mediate the ASER-specific down-regulation of the
      die-1 3'UTR. These three 25-bp sequence elements operate in both a redundant and
      combinatorial manner. Moreover, there are not only redundant elements within the
      die-1 3'UTR regulating its left/right asymmetric activity but asymmetric 3'UTR
      regulation is itself redundant with other regulatory mechanisms to achieve
      asymmetric DIE-1 protein expression and function in ASEL versus ASER. The
      features of 3'UTR regulation we describe here may apply to some of the vast
      number of genes in animal genomes whose expression is predicted to be regulated
      through their 3'UTR.

PMID- 20040593
TI  - Application of housekeeping npcRNAs for quantitative expression analysis of human
      transcriptome by real-time PCR.
AB  - In recent years the improvements in high-throughput gene expression analysis have
      led to the discovery of numerous non-protein-coding RNA (npcRNA) molecules. They
      form an abundant class of untranslated RNAs that have shown to play a crucial
      role in different biochemical pathways in the cell. Reverse transcription
      quantitative real-time polymerase chain reaction (RT-qPCR) is an efficient tool
      to measure RNA abundance and gene expression levels in tiny amounts of material.
      Despite its sensitivity, the lack of appropriate internal controls necessary for
      accurate data analysis is a limiting factor for its application in npcRNA
      research. Common internal controls applied are protein-coding reference genes,
      also termed "housekeeping" genes (HKGs). However, their expression levels
      reportedly vary among tissues and different experimental conditions. Moreover,
      application of HKGs as reference in npcRNA expression analyses is questionable,
      due to the differences in biogenesis. To address the issue of optimal RT-qPCR
      normalizers in npcRNA analysis, we performed a systematic evaluation of 18
      npcRNAs along with four common HKGs in 20 different human tissues. To determine
      the most suitable internal control with least expression variance, four
      evaluation strategies, geNORM, NormFinder, BestKeeper, and the comparative delta
      C(q) method, were applied. Our data strongly suggest that five npcRNAs, which we
      term housekeeping RNAs (HKRs), exhibit significantly better constitutive
      expression levels in 20 different human tissues than common HKGs. Determined HKRs
      are ideal candidates for RT-qPCR data normalization in human transcriptome
      analysis, and might also be used as reference genes irrespective of the nature of
      the genes under investigation.

PMID- 20040594
TI  - Cloning and characterization of dihydrofolate reductases from deep-sea bacteria.
AB  - Enzymes from organisms living in deep-sea are thought to have characteristic
      pressure-adaptation mechanisms in structure and function. To better understand
      these mechanisms in dihydrofolate reductase (DHFR), an essential enzyme in living
      cells, we cloned, overexpressed and purified four new DHFRs from the deep-sea
      bacteria Shewanella violacea (svDHFR), Photobacterium profundum (ppDHFR),
      Moritella yayanosii (myDHFR) and Moritella japonica (mjDHFR), and compared their
      structure and function with those of Escherichia coli DHFR (ecDHFR). These deep
      sea DHFRs showed 33-56% primary structure identity to ecDHFR while far
      ultraviolet circular dichroism and fluorescence spectra suggested that their
      secondary and tertiary structures were not largely different. The optimal
      temperature and pH for deep-sea DHFRs activity were lower than those of ecDHFR
      and different from each other. Deep-sea DHFRs kinetic parameters K(m) and k(cat)
      were larger than those of ecDHFR, resulting in 1.5-2.8-fold increase of
      k(cat)/K(m) except for mjDHFR which had a 28-fold decrease. The enzyme activity
      of ppDHFR and mjDHFR (moderate piezophilic bacteria) as well as ecDHFR decreased
      as pressure increased, while svDHFR and myDHFR (piezophilic bacteria) showed a
      significant tolerance to pressure. These results suggest that DHFRs from deep-sea
      bacteria possess specific enzymatic properties adapted to their life under high
      pressure.

PMID- 20040595
TI  - Roles of heterochromatin and telomere proteins in regulation of fission yeast
      telomere recombination and telomerase recruitment.
AB  - When the telomerase catalytic subunit (Trt1/TERT) is deleted, a majority of
      fission yeast cells survives by circularizing chromosomes. Alternatively, a small
      minority survives by maintaining telomeric repeats through recombination among
      telomeres. The recombination-based telomere maintenance in trt1Delta cells is
      inhibited by the telomere protein Taz1. In addition, catalytically inactive full
      length Trt1 (Trt1-CI) and truncated Trt1 lacking the T-motif and reverse
      transcriptase (RT) domain (Trt1-DeltaT/RT) can strongly inhibit recombination
      based survival. Here, we investigated the effects of deleting the heterochromatin
      proteins Swi6 (HP1 ortholog) and Clr4 (Suv39 family of histone
      methyltransferases) and the telomere capping complex subunits Poz1 and Ccq1 on
      Taz1- and Trt1-dependent telomere recombination inhibition. The ability of Taz1
      to inhibit telomere recombination did not require Swi6, Clr4, Poz1, or Ccq1.
      Although Swi6, Clr4, and Poz1 were dispensable for the inhibition of telomere
      recombination by Trt1-CI, Ccq1 was required for efficient telomere recruitment of
      Trt1 and Trt1-CI-dependent inhibition of telomere recombination. We also found
      that Swi6, Clr4, Ccq1, the checkpoint kinase Rad3 (ATR ortholog), and the
      telomerase regulatory subunit Est1 are all required for Trt1-DeltaT/RT to inhibit
      telomere recombination. However, because loss of Swi6, Clr4, Rad3, Ccq1, or Est1
      did not significantly alter the recruitment efficiency of Trt1-DeltaT/RT to
      telomeres, these factors are likely to enhance the ability of Trt1-DeltaT/RT to
      inhibit recombination-based survival by contributing to the negative regulation
      of telomere recombination.

PMID- 20040596
TI  - Appl1 is dispensable for mouse development, and loss of Appl1 has growth factor
      selective effects on Akt signaling in murine embryonic fibroblasts.
AB  - The adaptor protein APPL1 (adaptor protein containing pleckstrin homology (PH),
      phosphotyrosine binding (PTB), and leucine zipper motifs) was first identified as
      a binding protein of AKT2 by yeast two-hybrid screening. APPL1 was subsequently
      found to bind to several membrane-bound receptors and was implicated in their
      signal transduction through AKT and/or MAPK pathways. To determine the
      unambiguous role of Appl1 in vivo, we generated Appl1 knock-out mice. Here we
      report that Appl1 knock-out mice are viable and fertile. Appl1-null mice were
      born at expected Mendelian ratios, without obvious phenotypic abnormalities.
      Moreover, Akt activity in various fetal tissues was unchanged compared with that
      observed in wild-type littermates. Studies of isolated Appl1(-/-) murine
      embryonic fibroblasts (MEFs) showed that Akt activation by epidermal growth
      factor, insulin, or fetal bovine serum was similar to that observed in wild-type
      MEFs, although Akt activation by HGF was diminished in Appl1(-/-) MEFs. To rule
      out a possible redundant role played by the related Appl2, we used small
      interfering RNA to knock down Appl2 expression in Appl1(-/-) MEFs. Unexpectedly,
      cell survival was unaffected under normal culture conditions, and activation of
      Akt was unaltered following epidermal growth factor stimulation, although Akt
      activity did decrease further after HGF stimulation. Furthermore, we found that
      Appl proteins are required for HGF-induced cell survival and migration via
      activation of Akt. Our studies suggest that Appl1 is dispensable for development
      and only participate in Akt signaling under certain conditions.

PMID- 20040597
TI  - Down-regulation of the fetal stem cell factor SOX17 by H33342: a mechanism
      responsible for differential gene expression in breast cancer side population
      cells.
AB  - Human solid tumors contain rare cancer side population (SP) cells, which expel
      the fluorescent dye Hoechst 33342 (H33342) and display cancer stem cell
      characteristics. Transcriptional profiling of cancer SP cells isolated by H33342
      fluorescence analysis is a newly emerging approach to discover cancer stem cell
      markers and aberrant differentiation pathways. Using Affymetrix expression
      microarrays and quantitative reverse transcription-PCR, we investigated
      differential gene expression between SP and non-SP (NSP) cells isolated from
      human mammary carcinoma cell lines. A total of 136 genes were up-regulated in
      breast cancer SP relative to NSP cells, one of which was the fetal stem cell
      factor and Wnt/beta-catenin signaling pathway target SOX17. Strikingly, we
      discovered that SOX17 was down-regulated by H33342 in a dose-dependent manner. In
      SP cells, which expel H33342, down-regulation of SOX17 was less pronounced than
      in NSP cells, which retain H33342. As a result of this, SOX17 displayed a 10-20
      fold overexpression in cancer SP relative to NSP cells. Similar results were
      obtained for further stemness-related genes, namely EPC1 and SPRY1. These
      findings establish a previously unidentified gene-regulatory impact of H33342 as
      a novel mechanism responsible for differential gene expression in cancer SP
      cells. This has significant implications for the future interpretation of cancer
      SP cells.

PMID- 20040598
TI  - Identification and biochemical characterization of molybdenum cofactor-binding
      proteins from Arabidopsis thaliana.
AB  - The molybdenum cofactor (Moco) forms part of the catalytic center in all
      eukaryotic molybdenum enzymes and is synthesized in a highly conserved pathway.
      Among eukaryotes, very little is known about the processes taking place
      subsequent to Moco biosynthesis, i.e. Moco transfer, allocation, and insertion
      into molybdenum enzymes. In the model plant Arabidopsis thaliana, we identified a
      novel protein family consisting of nine members that after recombinant expression
      are able to bind Moco with K(D) values in the low micromolar range and are
      therefore named Moco-binding proteins (MoBP). For two of the nine proteins atomic
      structures are available in the Protein Data Bank. Surprisingly, both crystal
      structures lack electron density for the C terminus, which may indicate a high
      flexibility of this part of the protein. C-terminal truncated MoBPs showed
      significantly decreased Moco binding stoichiometries. Experiments where the MoBP
      C termini were exchanged among MoBPs converted a weak Moco-binding MoBP into a
      strong binding MoBP, thus indicating that the MoBP C terminus, which is encoded
      by a separate exon, is involved in Moco binding. MoBPs were able to enhance Moco
      transfer to apo-nitrate reductase in the Moco-free Neurospora crassa mutant nit
      1. Furthermore, we show that the MoBPs are localized in the cytosol and undergo
      protein-protein contact with both the Moco donor protein Cnx1 and the Moco
      acceptor protein nitrate reductase under in vivo conditions, thus indicating for
      the MoBPs a function in Arabidopsis cellular Moco distribution.

PMID- 20040599
TI  - Regulation of E2F1-induced apoptosis by the nucleolar protein RRP1B.
AB  - Regulation of the E2F family of transcription factors is important in control of
      cellular proliferation; dysregulation of the E2Fs is a hallmark of many cancers.
      One member of the E2F family, E2F1, also has the paradoxical ability to induce
      apoptosis; however, the mechanisms underlying this selectivity are not fully
      understood. We now identify a nucleolar protein, RRP1B, as an E2F1-specific
      transcriptional target. We characterize the RRP1B promoter and demonstrate its
      selective response to E2F1. Consistent with the activation of E2F1 activity upon
      DNA damage, RRP1B is induced by several DNA-damaging agents. Importantly, RRP1B
      is required for the expression of certain E2F1 proapoptotic target genes and the
      induction of apoptosis by DNA-damaging agents. This activity is mediated in part
      by complex formation between RRP1B and E2F1 on selective E2F1 target gene
      promoters. Interaction between RRP1B and E2F1 can be found inside the nucleolus
      and diffuse nucleoplasmic punctates. Thus, E2F1 makes use of its transcriptional
      target RRP1B to activate other genes directly involved in apoptosis. Our data
      also suggest an underappreciated role for nucleolar proteins in transcriptional
      regulation.

PMID- 20040600
TI  - Direct observation and quantitative analysis of Lck exchange between plasma
      membrane and cytosol in living T cells.
AB  - Palmitoylation represents a common motif for anchorage of cytosolic proteins to
      the plasma membrane. Being reversible, it allows for controlled exchange between
      cytosolic and plasma membrane-bound subpopulations. In this study, we present a
      live cell single molecule approach for quantifying the exchange kinetics of
      plasma membrane and cytosolic populations of fluorescently labeled Lck, the key
      Src family kinase involved in early T cell signaling. Total internal reflection
      (TIR) fluorescence microscopy was employed for confining the analysis to membrane
      proximal molecules. Upon photobleaching Lck-YFP in TIR configuration,
      fluorescence recovery proceeds first via the cytosol outside of the evanescent
      field, so that in the early phase fluorescence signal arises predominantly from
      membrane-proximal cytosolic Lck. The diffusion constant of each molecule allowed
      us to distinguish whether the molecule has already associated with the plasma
      membrane or was still freely diffusing in the cytosol. From the number of
      molecules that inserted during the recovery time we quantified the insertion
      kinetics: on average, membrane-proximal molecules within the evanescent field
      needed approximately 400 ms to be inserted. The average lifetime of Lck in the
      plasma membrane was estimated at 50 s; together with the mobility of 0.26
      microm(2)/s this provides sufficient time to explore the surface of the whole T
      cell before dissociation into the cytosol. Experiments on palmitoylation
      deficient Lck mutants yielded similar on-rates, but substantially increased off
      rates. We discuss our findings based on a model for the plasma membrane
      association and dissociation kinetics of Lck, which accounts for reversible
      palmitoylation on cysteine 3 and 5.

PMID- 20040601
TI  - A volume regulatory response can be triggered by nucleosides in human
      erythrocytes, a perfect osmometer no longer.
AB  - Human erythrocytes have been regarded as perfect osmometers, which swell or
      shrink as dictated by their osmotic environment. In contrast, in most other
      cells, swelling elicits a regulatory volume decrease (RVD) modulated by the
      activation of purinic and pyrimidinic receptors (P receptors). For human
      erythrocytes this modulation has not been tested, and we thus investigated
      whether P receptor activation can induce RVD in these cells. Further, because
      ectonucleotidases may scavenge ATP or ADP or act as a source for extracellular
      adenosine and therefore modulate P receptor activation and RVD, we also
      determined their activity in intact erythrocytes. We found relatively low
      ectoATPase but significant ectoADPase and ectoAMPase activities. When
      erythrocytes were exposed to hypotonic medium alone, they swelled as expected for
      an osmometric response and showed no RVD. Activation of P2 receptors by exogenous
      ATP or ADP did not trigger RVD, whereas P1 agonists adenosine and adenosine-5'-N
      ethylcarboxamide induced significant RVD. The effect of adenosine-5'-N
      ethylcarboxamide was dose-dependent (maximal RVD of 27%; apparent K((1/2)) of 1.6
      +/- 1.7 microM). The RVD induced by adenosine was blocked 80% with the non
      selective P1 antagonist 8-(p-sulfophenyl theophylline) or the P1-A(2B) inhibitor
      MRS1754, but not by inhibitors of P1 subtypes A(1), A(2A), and A(3). In addition,
      forskolin (an inducer of intracellular cAMP formation) could mimic the effect of
      adenosine, supporting the idea of P1-A(2B) receptor activation. In conclusion, we
      report a novel P1-A(2B) receptor-mediated RVD activation in mature human
      erythrocytes and thus indicate that these long held perfect osmometers are not so
      perfect after all.

PMID- 20040602
TI  - TDP-43 is a developmentally regulated protein essential for early embryonic
      development.
AB  - TDP-43 is a DNA/RNA-binding protein implicated in multiple steps of
      transcriptional and post-transcriptional regulation of gene expression.
      Alteration of this multifunctional protein is associated with a number of
      neurodegenerative diseases including amyotrophic lateral sclerosis and
      frontotemporal lobar degeneration with ubiquitin positive inclusions. Whereas a
      pathological link to neurodegenerative disorders has been established, the
      cellular and physiological functions of TDP-43 remain unknown. In this study, we
      show that TDP-43 is a nuclear protein with persistent high-level expression
      during embryonic development and with progressively decreased protein levels
      during postnatal development. In mice where the TDP-43 gene (Tardbp) was
      disrupted using a gene trap that carries a beta-galactosidase marker gene,
      heterozygous (Tardbp(+/-)) mice are fertile and healthy, but intercrosses of
      Tardbp(+/-) mice yielded no viable homozygotic null (Tardbp(-/-)) mice. Indeed,
      Tardbp(-/-) embryos die between 3.5 and 8.5 days of development. Tardbp(-/-)
      blastocysts grown in cell culture display abnormal expansion of their inner cell
      mass. The pattern of beta-galactosidase staining at E9.5 Tardbp(+/-) embryos is
      predominantly restricted to the neuroepithelium and remains prominent in neural
      progenitors at E10.5-12.5. TDP-43 is detected in spinal cord progenitors and in
      differentiated motor neurons as well as in the dorsal root ganglia at E12.5. Beta
      galactosidase staining of tissues from adult Tardbp(+/-) mice shows widespread
      expression of TDP-43, including prominent levels in various regions of the
      central nervous system afflicted in neurodegenerative disorders. These results
      indicate that TDP-43 is developmentally regulated and indispensible for early
      embryonic development.

PMID- 20040603
TI  - Preferential KAT1-KAT2 heteromerization determines inward K+ current properties
      in Arabidopsis guard cells.
AB  - Guard cells adjust their volume by changing their ion content due to intense
      fluxes that, for K(+), are believed to flow through inward or outward Shaker
      channels. Because Shaker channels can be homo- or heterotetramers and Arabidopsis
      guard cells express at least five genes encoding inward Shaker subunits,
      including the two major ones, KAT1 and KAT2, the molecular identity of inward
      Shaker channels operating therein is not yet completely elucidated. Here, we
      first addressed the properties of KAT1-KAT2 heteromers by expressing KAT1-KAT2
      tandems in Xenopus oocytes. Then, computer analyses of the data suggested that
      coexpression of free KAT1 and KAT2 subunits resulted mainly in heteromeric
      channels made of two subunits of each type due to some preferential association
      of KAT1-KAT2 heterodimers at the first step of channel assembly. This was further
      supported by the analysis of KAT2 effect on KAT1 targeting in tobacco cells.
      Finally, patch-clamp recordings of native inward channels in wild-type and mutant
      genotypes strongly suggested that this preferential heteromerization occurs in
      planta and that Arabidopsis guard cell inward Shaker channels are mainly
      heteromers of KAT1 and KAT2 subunits.

PMID- 20040604
TI  - Recombinant human collagen XV regulates cell adhesion and migration.
AB  - The C-terminal end of collagen XV, restin, has been the focus of several studies,
      but the functions of full-length collagen XV have remained unknown. We describe
      here studies on the production, purification, and function of collagen XV and the
      production of a monoclonal N-terminal antibody to it. Full-length human collagen
      XV was produced in insect cells using baculoviruses and purified from the cell
      culture medium. The yield was 15 mg/liter of cell culture medium. The collagen XV
      was shown to be trimeric, with disulfide bonds in the collagenous region. Rotary
      shadowing electron microscopy revealed rod-like molecules with a mean length of
      241.8 nm and with a globular domain at one end. The globular domain was verified
      to be the N-terminal end by N-terminal antibody binding. The molecules show
      flexibility in their conformation, presumably due to the many interruptions in
      their collagenous domains. The ability of collagen XV to serve as a substrate for
      cells was tested in cell adhesion assays, and it was shown that cells did not
      bind to collagen XV-coated surfaces. When added to the culture medium of
      fibroblasts and fibrosarcoma cells, however, collagen XV rapidly bound to their
      fibronectin network. Solid phase assays showed that collagen XV binds to
      fibronectin, laminin, and vitronectin and that it binds to the collagen/gelatin
      binding domain of fibronectin. No binding was detected to fibrillar collagens,
      fibril-associated collagens, or decorin. Interestingly, collagen XV was found to
      inhibit the adhesion and migration of fibrosarcoma cells when present in
      fibronectin-containing matrices.

PMID- 20040605
TI  - Measuring the transition readiness of youth with special healthcare needs:
      validation of the TRAQ--Transition Readiness Assessment Questionnaire.
AB  - OBJECTIVE: The aim of this study was to develop the Transition Readiness
      Assessment Questionnaire (TRAQ), a measure of readiness for transition from
      pediatric to adult healthcare for youth with special health care needs (YSHCN).
      METHODS: We administered TRAQ to 192 YSHCN aged 16-26 years in three primary
      diagnostic categories, conducted factor analysis, and assessed differences in
      TRAQ scores by age, gender, race, and primary diagnosis type. RESULTS: Factor
      analysis identified two TRAQ domains with high internal consistency: Skills for
      Self-Management and Skills for Self-Advocacy. Each domain had high internal
      consistency. In multivariate regression models, older age and a primary diagnosis
      of an activity limiting physical condition were associated with higher scores in
      Self-Management, and female gender and a primary diagnosis of an activity
      limiting physical condition were associated with higher scores in Self-Advocacy.
      CONCLUSIONS: Our initial validation study suggests the TRAQ is a useful tool to
      assess transition readiness in YSHCN and to guide educational interventions by
      providers to support transition.

PMID- 20040606
TI  - Brief report: Maternal kangaroo care for neonatal pain relief: a systematic
      narrative review.
AB  - OBJECTIVE: To appraise critically and to synthesize existing Maternal Kangaroo
      Care (MKC) intervention studies for neonatal procedural pain. METHODS: Four
      electronic databases were systematically searched and eligible studies selected
      by two independent reviewers. Of 93 abstracts, 12 studies met the inclusion
      criteria. Findings were extracted and methodology assessed based on best
      synthesis methodology. RESULTS: There is evidence that MKC can significantly
      reduce pain from a single pain procedure in full-term infants and stable preterm
      infants (>26 weeks GA). All 12 MKC studies reported significant reduction in pain
      behavior but measures of heart rate varied. However, current approaches to data
      analysis cannot tell us of the magnitude of treatment effects. CONCLUSIONS:
      Future studies need to clearly define their intervention, provide a guiding
      framework, explain their study methods and analyses and report effect sizes. This
      will help strengthen validity of the intervention and support recommendations for
      clinical application.

PMID- 20040607
TI  - The HIV experience: youth identified barriers for transitioning from pediatric to
      adult care.
AB  - OBJECTIVE: The aim of this study was to explore the experiences of youth living
      with HIV who transitioned from pediatric to adult care. METHODS: Semi-structured
      telephone interviews were conducted with 59 youth (mean age = 22 years) living
      with HIV about the transition experience, demographics, and health status.
      RESULTS: Of youth who transitioned to adult care, immune function (CD4) trended
      downward, 45% found the transition more difficult than anticipated, and 32% could
      not find emotional support services. Youth identified the need for increased
      continuity of care, assistance with logistics, improved communication with
      providers and caregivers, and individualized management of their transition
      process. CONCLUSION: Without adequate preparation, the transition process can be
      compromised with potentially serious health consequences. Youth living with HIV
      seek adult providers that can provide developmentally appropriate transition
      interventions that address loss, disclosure, and sexual behavior along with
      medical needs.

PMID- 20040608
TI  - Extubation of patients with neuromuscular weakness: a new management paradigm.
AB  - BACKGROUND: Successful extubation conventionally necessitates the passing of
      spontaneous breathing trials (SBTs) and ventilator weaning parameters. We report
      successful extubation of patients with neuromuscular disease (NMD) and weakness
      who could not pass them. METHODS: NMD-specific extubation criteria and a new
      extubation protocol were developed. Data were collected on 157 consecutive
      "unweanable" patients, including 83 transferred from other hospitals who refused
      tracheostomies. They could not pass the SBTs before or after extubation. Once the
      pulse oxyhemoglobin saturation (Spo(2)) was maintained at > or = 95% in ambient
      air, patients were extubated to full noninvasive mechanical ventilation (NIV)
      support and aggressive mechanically assisted coughing (MAC). Rather than oxygen,
      NIV and MAC were used to maintain or return the Spo(2) to > or = 95%. Extubation
      success was defined as not requiring reintubation during the hospitalization and
      was considered as a function of diagnosis, preintubation NIV experience, and
      vital capacity and assisted cough peak flows (CPF) at extubation. RESULTS: Before
      hospitalization 96 (61%) patients had no experience with NIV, 41 (26%) used it <
      24 h per day, and 20 (13%) were continuously NIV dependent. The first-attempt
      protocol extubation success rate was 95% (149 patients). All 98 extubation
      attempts on patients with assisted CPF > or = 160 L/m were successful. The
      dependence on continuous NIV and the duration of dependence prior to intubation
      correlated with extubation success (P < .005). Six of eight patients who
      initially failed extubation succeeded on subsequent attempts, so only two with no
      measurable assisted CPF underwent tracheotomy. CONCLUSIONS: Continuous volume
      cycled NIV via oral interfaces and masks and MAC with oximetry feedback in
      ambient air can permit safe extubation of unweanable patients with NMD.

PMID- 20040609
TI  - Coagulopathy does not protect against venous thromboembolism in hospitalized
      patients with chronic liver disease.
AB  - BACKGROUND: It is uncertain whether pathologically prolonged international
      normalized ratio (INR) seen in chronic liver disease (CLD) protects against
      venous thromboembolism (VTE). Previous studies reported VTE incidence of 0.5% to
      1.9% in patients with CLD. We sought to evaluate VTE incidence among hospitalized
      patients with CLD according to INR levels. METHODS: This was a retrospective
      cohort study performed at a tertiary university hospital. We included all adult
      patients admitted with a primary diagnosis of CLD over a 7-year period. The
      primary outcome was the development of VTE during hospital stay. Patients were
      divided into quartiles according to their highest admission INR. VTE events and
      prophylaxis rates were compared among INR quartiles. RESULTS: During the allotted
      7-year period, we included 190 patients. Of these, 12 developed VTE events,
      yielding a VTE incidence of 6.3%. There was no significant difference in the
      incidence of VTE between INR quartiles. Hospital mortality rates were higher in
      the higher INR quartiles than in the lower ones (P < .001), but hospital length
      of stay was not significantly different. Of the patients with documented VTE, one
      (4.2%) was Child-Pugh stage A, three (4.6%) were stage B, and eight (8.0%) were
      stage C (P = .602). VTE prophylaxis was not used in 75% of patients. CONCLUSIONS:
      An elevated INR in the setting of CLD does not appear to protect against the
      development of hospital-acquired VTE. The notion that "auto-anticoagulation"
      protects against VTE is unfounded. Use of DVT prophylaxis was extremely low in
      this population.

PMID- 20040610
TI  - Advantages of endurance treadmill walking compared with cycling to assess
      bronchodilator therapy.
AB  - BACKGROUND: Walking is a familiar daily activity that is generally limited by
      breathlessness, whereas cycling is an uncommon physical effort typically limited
      by leg discomfort. The hypothesis was that patients with COPD would exhibit
      greater improvements in exercise endurance and relief of breathlessness with
      bronchodilator therapy during treadmill walking compared with cycling. METHODS:
      In this randomized, 2 x 2, double-blind, placebo-controlled, crossover trial, 20
      patients with COPD (age, 64 +/- 7 years; FEV(1), 56 +/- 14% predicted) performed
      constant-load endurance exercise on the treadmill and cycle ergometer at 85% of
      capacity after inhaling normal saline (NS) or arformoterol (ARF) (15 microg).
      RESULTS: Increases in endurance times and consistency of responses were greater
      with treadmill walking (Delta: 157 +/- 286 s; P = .024; 80% improved) than with
      cycle exercise (Delta: 110 +/- 219 s; P = .038; 65% improved) with ARF compared
      with NS. However, these changes were not significantly different. The slope of
      breathlessness-time (mean Delta = -29%; P = .007) and the magnitude of oxygen
      desaturation were significantly lower with ARF compared with NS during treadmill,
      but not cycle, exercise. Inspiratory capacity values were similar between modes
      of exercise when comparing the same study medication. CONCLUSIONS: Improved
      endurance times support both constant-load treadmill and cycle exercise to assess
      the efficacy of bronchodilator therapy in patients with COPD. Unique differences
      in physiologic and perceptual responses with bronchodilation demonstrate
      advantages of treadmill walking as an exercise stimulus. TRIAL REGISTRATION:
      clinicaltrials.gov; Identifier: NCT00754546.

PMID- 20040611
TI  - Measurement of COPD severity using a survey-based score: validation in a
      clinically and physiologically characterized cohort.
AB  - BACKGROUND: A comprehensive survey-based COPD severity score has usefulness for
      epidemiologic and health outcomes research. We previously developed and validated
      the survey-based COPD Severity Score without using lung function or other
      physiologic measurements. In this study, we aimed to further validate the
      severity score in a different COPD cohort and using a combination of patient
      reported and objective physiologic measurements. METHODS: Using data from the
      Function, Living, Outcomes, and Work cohort study of COPD, we evaluated the
      concurrent and predictive validity of the COPD Severity Score among 1,202
      subjects. The survey instrument is a 35-point score based on symptoms, medication
      and oxygen use, and prior hospitalization or intubation for COPD. Subjects were
      systemically assessed using structured telephone survey, spirometry, and 6-min
      walk testing. RESULTS: We found evidence to support concurrent validity of the
      score. Higher COPD Severity Score values were associated with poorer FEV(1) (r = 
      0.38), FEV(1)% predicted (r = -0.40), Body mass, Obstruction, Dyspnea, Exercise
      Index (r = 0.57), and distance walked in 6 min (r = -0.43) (P < .0001 in all
      cases). Greater COPD severity was also related to poorer generic physical health
      status (r = -0.49) and disease-specific health-related quality of life (r = 0.57)
      (P < .0001). The score also demonstrated predictive validity. It was also
      associated with a greater prospective risk of acute exacerbation of COPD defined
      as ED visits (hazard ratio [HR], 1.31; 95% CI, 1.24-1.39), hospitalizations (HR,
      1.59; 95% CI, 1.44-1.75), and either measure of hospital-based care for COPD (HR,
      1.34; 95% CI, 1.26-1.41) (P < .0001 in all cases). CONCLUSION: The COPD Severity
      Score is a valid survey-based measure of disease-specific severity, both in terms
      of concurrent and predictive validity. The score is a psychometrically sound
      instrument for use in epidemiologic and outcomes research in COPD.

PMID- 20040612
TI  - Tuberculin skin test and in vitro assays provide complementary measures of
      antimycobacterial immunity in children and adolescents.
AB  - BACKGROUND: Although many studies have compared in vitro TB diagnostic tests with
      the venerable tuberculin skin test (TST), there is little understanding of the
      quantitative relationship between critical measures of antimycobacterial immunity
      used to detect TB infection. We, therefore, decided to determine the degree of
      redundancy between quantitative read-outs of in vivo and in vitro assays of
      antimycobacterial immunity. METHODS: We enrolled 475 healthy HIV-negative
      children and young adults living in a hyperendemic area of TB. We measured in
      vivo TST responses, and a 1:10 diluted 3- or 7-day whole-blood assay was used to
      determine the in vitro antigen-specific interferon (IFN)-gamma cytokine release.
      The frequency of antigen-specific IFN-gamma(+)CD4(+) and IFN-gamma(+)CD8(+) cells
      was tested using intracellular cytokine staining after 1 day incubation. RESULTS:
      In vivo TST responses segregated into two well-separated groups with either no
      measurable response (TST induration < 5 mm; n = 164) or a normally distributed
      group with TST indurations > or = 5 mm with peak at 15 mm (n = 260). In vitro
      assays provided a less pronounced separation of responders and nonresponders.
      Correlation analysis of responses among persons with TST > or = 5 mm demonstrated
      that extent of TST response was poorly correlated with IFN-gamma release
      (coefficients of correlation rho = 0.17-0.22) and frequency of IFN
      gamma(+)CD4(+)/CD8(+) cells (rho = 0.05-0.17) across three stimulating antigens
      (Mycobacterium bovis bacillus Calmette-Guerin, purified protein derivative, early
      secreted antigenic target-6). CONCLUSION: We conclude that in vivo and in vitro
      assays are nonredundant, complementary measures of antimycobacterial immunity.
      Both TST and in vitro assays provided valuable information about
      antimycobacterial immunity and by inference latent TB in the studied high
      incidence TB settings.

PMID- 20040614
TI  - Religious belief as compensatory control.
AB  - The authors review experimental evidence that religious conviction can be a
      defensive source of compensatory control when personal or external sources of
      control are low. They show evidence that (a) belief in religious deities and
      secular institutions can serve as external forms of control that can compensate
      for manipulations that lower personal control and (b) religious conviction can
      also serve as compensatory personal control after experimental manipulations that
      lower other forms of personal or external control. The authors review
      dispositional factors that differentially orient individuals toward external or
      personal varieties of compensatory control and conclude that compensatory
      religious conviction can be a flexible source of personal and external control
      for relief from the anxiety associated with random and uncertain experiences.

PMID- 20040613
TI  - Ageing and endothelial progenitor cell release of proangiogenic cytokines.

PMID- 20040615
TI  - Digital fetal aneuploidy diagnosis by next-generation sequencing.

PMID- 20040616
TI  - High-sensitivity cardiac troponin: hype, help, and reality.

PMID- 20040617
TI  - Implementation of a closed-loop reporting system for critical values and clinical
      communication in compliance with goals of the joint commission.
AB  - BACKGROUND: Current practices of reporting critical laboratory values make it
      challenging to measure and assess the timeliness of receipt by the treating
      physician as required by The Joint Commission's 2008 National Patient Safety
      Goals. METHODS: A multidisciplinary team of laboratorians, clinicians, and
      information technology experts developed an electronic ALERTS system that reports
      critical values via the laboratory and hospital information systems to
      alphanumeric pagers of clinicians and ensures failsafe notification, instant
      documentation, automatic tracking, escalation, and reporting of critical value
      alerts. A method for automated acknowledgment of message receipt was incorporated
      into the system design. RESULTS: The ALERTS system has been applied to inpatients
      and eliminated approximately 9000 phone calls a year made by medical
      technologists. Although a small number of phone calls were still made as a result
      of pages not acknowledged by clinicians within 10 min, they were made by
      telephone operators, who either contacted the same physician who was initially
      paged by the automated system or identified and contacted alternate physicians or
      the patient's nurse. Overall, documentation of physician acknowledgment of
      receipt in the electronic medical record increased to 95% of critical values over
      9 months, while the median time decreased to <3 min. CONCLUSIONS: We improved
      laboratory efficiency and physician communication by developing an electronic
      system for reporting of critical values that is in compliance with The Joint
      Commission's goals.

PMID- 20040618
TI  - Large-scale medical resequencing for X-linked mental retardation.

PMID- 20040619
TI  - Detection of drug-resistant clones in chronic myelogenous leukemia patients
      during dasatinib and nilotinib treatment.
AB  - BACKGROUND: Imatinib effectively inhibits the tyrosine kinase activity conferred
      by the BCR-ABL gene [fusion gene of BCR (breakpoint cluster region) and ABL1 (c
      abl oncogene 1, receptor tyrosine kinase)] and thereby appreciably improves
      outcomes for chronic myelogenous leukemia (CML). A small percentage of patients
      relapse because of the proliferation of escape clones; such relapses can be
      treated with second-generation drugs. Early detection and monitoring of resistant
      clones may provide clinical benefit. We describe the development and testing of a
      new approach for quantitative monitoring of CML resistance. METHODS: We designed
      mutation-specific assays that use hydrolysis probes and an array of allele
      specific primers containing nucleotides mismatched at various positions. All
      assays were tested with plasmids containing corresponding mutant or wild-type
      sequences, allowing identification of optimal assays for specific and effective
      amplification of the target template. Clinical samples were then used to compare
      the results of selected assays with those of standard genotyping. RESULTS: We
      used a modified amplification refractory mutational system approach and testing
      with plasmid constructs to design assays that allowed highly selective detection
      of resistance for all target mutations. By taking advantage of single-step
      performance and high PCR efficiency, we were able to quantitatively track the
      absolute amount of resistance conferred by a specific mutation over 4 orders of
      magnitude. Moreover, we designed an integrated test for dasatinib resistance that
      uses multiple primers simultaneously. CONCLUSIONS: These single-step, closed-tube
      assays specifically target mutations associated with resistance to dasatinib or
      nilotinib. Compared with standard genotyping, such biased genotyping improves the
      detection of resistance or alternative features via quantitative analysis of the
      absolute amount of resistance.

PMID- 20040620
TI  - Newborn screening for cystic fibrosis by use of a multiplex immunoassay.
AB  - BACKGROUND: Since its beginnings, newborn screening for cystic fibrosis (CF)
      using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high
      rate of false-positive results (screen positive, diagnosis negative), despite
      attempts to reduce this rate by use of altered cutoffs and second-tier DNA
      testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely
      aligned with pancreatic disease, including CF. Assay standardization between
      programs is a continuing problem because the IRT assays currently in use
      variously recognize either 1 or both isoforms. Here we report the development of
      a multiplexed assay for both forms of IRT simultaneously. METHODS: Using 2
      different Luminex bead sets, we developed assays for each IRT isoform separately
      and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we
      compared the results with a CF kit currently in use. RESULTS: In a sample set
      consisting of 16 cases confirmed positive for CF, we established a cutoff at >97
      microg/L total IRT. Seven of 8 carriers with 1 CF mutation screen-positive by the
      standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen
      positive by standard IRT, 11 were screen-negative by IRT1+IRT2. None of these 11
      cases had CF mutations identified by the screening program. CONCLUSIONS: These
      data indicate that the multiplex method with specificity for 2 isoforms of IRT
      has performance comparable to that of a standard IRT method and the advantage of
      improved standardization by detection of the 2 isoforms.

PMID- 20040621
TI  - Assessment of vitamin B(12) absorption based on the accumulation of orally
      administered cyanocobalamin on transcobalamin.
AB  - BACKGROUND: Vitamin B(12), or cobalamin (Cbl), is absorbed in the intestine and
      transported to the cells bound to transcobalamin (TC). We hypothesize that
      cyanocobalamin (CNCbl) is absorbed unchanged, thereby allowing measurement of the
      complex of CNCbl bound to TC (TC-CNCbl) to be used for studying the absorption of
      the vitamin. METHODS: TC was immunoprecipitated from serum samples obtained from
      healthy donors at baseline and at 24 h after oral administration of three 9
      microg CNCbl doses over 1 day. Cbl was released by treatment with subtilisin
      Carlsberg. The different forms of Cbl were isolated by HPLC and subsequently
      quantified with an ELISA-based Cbl assay. RESULTS: At baseline, the median TC
      CNCbl concentration was 1 pmol/L (range, 0-10 pmol/L); the intraindividual
      variation (SD) was 1.6 pmol/L (n = 31). After CNCbl administration, the TC-CNCbl
      concentration increased significantly (P = 0.0003, paired t-test), whereas no
      major changes were observed in any of the other Cbl forms bound to TC (n = 10).
      Only a moderate additional increase in TC-CNCbl was observed with prolonged (5
      days) CNCbl administration (n = 10). We designed an absorption test based on
      measuring TC-CNCbl at baseline and 24 h after CNCbl intake and established a
      reference interval for the increase in TC-CNCbl (n = 78). The median absolute
      increase was 23 pmol/L (range, 6-64 pmol/L), and the relative increase was >3
      fold. CONCLUSIONS: Our data demonstrate that CNCbl is absorbed unchanged and
      accumulates on circulating TC. We suggest that measuring TC-CNCbl will improve
      the assessment of vitamin B(12) absorption.

PMID- 20040622
TI  - Proteomics research to discover markers: what can we learn from Netflix?
AB  - BACKGROUND: Research in the field of proteomics to discover markers for detection
      of cancer has produced disappointing results, with few markers gaining US Food
      and Drug Administration approval, and few claims borne out when subsequently
      tested in rigorous studies. What is the role of better mathematical or
      statistical analysis in improving the situation? CONTENT: This article examines
      whether a recent successful Netflix-sponsored competition using mathematical
      analysis to develop a prediction model for movie ratings of individual
      subscribers can serve to improve studies of markers in the field of proteomics.
      Netflix developed a database of movie preferences of individual subscribers using
      a longitudinal cohort research design. Groups of researchers then competed to
      develop better ways to analyze the data. Against this background, the strengths
      and weaknesses of research design are reviewed, contrasting the Netflix design
      with that of studies of biomarkers to detect cancer. Such biomarker studies
      generally have less-strong design, lower numbers of outcomes, and greater
      difficulty in even just measuring predictors and outcomes, so the fundamental
      data that will be used in mathematical analysis tend to be much weaker than in
      other kinds of research. CONCLUSIONS: If the fundamental data that will be
      analyzed are not strong, then better analytic methods have limited use in
      improving the situation. Recognition of this situation is an important first step
      toward improving the quality of clinical research about markers to detect cancer.

PMID- 20040623
TI  - Sharply increased serum free light-chain concentrations after treatment for
      multiple myeloma.

PMID- 20040624
TI  - Commentary.

PMID- 20040625
TI  - Commentary.

PMID- 20040630
TI  - Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat
      lipopolysaccharide model of neuroinflammation.
AB  - Neuroinflammation, caused by 6 days of intracerebroventricular infusion of a low
      dose of lipopolysaccharide (LPS; 0.5 ng/h), stimulates brain arachidonic acid
      (AA) metabolism in rats, but 6 weeks of lithium pretreatment reduces this effect.
      To further understand this action of lithium, we measured concentrations of
      eicosanoids and docosanoids generated from AA and docosahexaenoic acid (DHA),
      respectively, in high-energy microwaved rat brain using LC/MS/MS and two doses of
      LPS. In rats fed a lithium-free diet, low (0.5 ng/h)- or high (250 ng/h)-dose LPS
      compared with artificial cerebrospinal fluid increased brain unesterified AA and
      prostaglandin E(2) concentrations and activities of AA-selective Ca(2+)-dependent
      cytosolic phospholipase A(2) (cPLA(2))-IV and Ca(2+)-dependent secretory sPLA(2).
      LiCl feeding prevented these increments. Lithium had a significant main effect by
      increasing brain concentrations of lipoxygenase-derived AA metabolites, 5-
      hydroxyeicosatetraenoic acid (HETE), 5-oxo-eicosatetranoic acid, and 17-hydroxy
      DHA by 1.8-, 4.3- and 1.9-fold compared with control diet. Lithium also increased
      15-HETE in high-dose LPS-infused rats. Ca(2+)-independent iPLA(2)-VI activity and
      unesterified DHA and docosapentaenoic acid (22:5n-3) concentrations were
      unaffected by LPS or lithium. This study demonstrates, for the first time, that
      lithium can increase brain 17-hydroxy-DHA formation, indicating a new and
      potentially important therapeutic action of lithium.

PMID- 20040632
TI  - Taking action to save lives.

PMID- 20040631
TI  - The gut microbiota modulates host energy and lipid metabolism in mice.
AB  - The gut microbiota has recently been identified as an environmental factor that
      may promote metabolic diseases. To investigate the effect of gut microbiota on
      host energy and lipid metabolism, we compared the serum metabolome and the
      lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R)
      and germ-free mice. The serum metabolome of CONV-R mice was characterized by
      increased levels of energy metabolites, e.g., pyruvic acid, citric acid, fumaric
      acid, and malic acid, while levels of cholesterol and fatty acids were reduced.
      We also showed that the microbiota modified a number of lipid species in the
      serum, adipose tissue, and liver, with its greatest effect on triglyceride and
      phosphatidylcholine species. Triglyceride levels were lower in serum but higher
      in adipose tissue and liver of CONV-R mice, consistent with increased lipid
      clearance. Our findings show that the gut microbiota affects both host energy and
      lipid metabolism and highlights its role in the development of metabolic
      diseases.

PMID- 20040633
TI  - DVT prophylaxis: confronting a public health menace.

PMID- 20040634
TI  - Can the events of early life influence the development of rheumatoid arthritis?

PMID- 20040635
TI  - On anti-tumor necrosis factor-induced systemic lupus erythematosus.

PMID- 20040636
TI  - A novel composite endpoint to evaluate the gastrointestinal effects of NSAID
      through the entire GI tract: introducing CSULGIE.

PMID- 20040637
TI  - Images in rheumatology. Transfusion-related acute lung injury during intravenous
      immunoglobulin treatment.

PMID- 20040638
TI  - Images in rheumatology. Heel enthesopathy of diffuse idiopathic skeletal
      hyperostosis resembling enthesitis of spondyloarthritis.

PMID- 20040639
TI  - Images in rheumatology. Severe adult-onset calcinosis in a patient with a history
      of juvenile dermatomyositis.

PMID- 20040640
TI  - Philip Hench, a Nobel link in the evolution of the Canada Gairdner International
      Awards.

PMID- 20040642
TI  - Risk factors for cardiovascular disease in rheumatoid arthritis: defining
      treatment thresholds.

PMID- 20040643
TI  - Low molecular weight heparin and aspirin for recurrent pregnancy loss: results
      from the HepASA trial.

PMID- 20040644
TI  - Induction of systemic lupus erythematosus with tumor necrosis factor blockers.

PMID- 20040645
TI  - HLA-DRB1 alleles and rheumatoid arthritis-related pulmonary fibrosis.

PMID- 20040646
TI  - Low level (below cutoff) of anti-cyclic citrullinated peptide test results in
      diagnosis of rheumatoid arthritis in a high-risk population.

PMID- 20040647
TI  - Successful use of etanercept in acquired angioedema in a patient with psoriatic
      arthritis.

PMID- 20040648
TI  - Recommended screening strategy for preventing tuberculosis flare in patients with
      inflammatory rheumatic diseases receiving tumor necrosis factor-alpha inhibitors
      in India - followup report.

PMID- 20040649
TI  - Abrupt development of sarcoidosis with a prodromal increase in plasma osteopontin
      in a patient with rheumatoid arthritis during treatment with etanercept.

PMID- 20040650
TI  - Inflammatory arthritis in a patient with primary biliary cirrhosis: B cell
      mediated synovitis.

PMID- 20040651
TI  - Antineutrophil cytoplasmic antibody-positive digital necrosis in a patient with
      limited systemic sclerosis.

PMID- 20040652
TI  - Preconception counseling in women with diabetes: a population-based study in the
      north of England.
AB  - OBJECTIVE To investigate the association of preconception counseling with markers
      of care and maternal characteristics in women with pregestational diabetes.
      RESEARCH DESIGN AND METHODS The study includes data from a regional multi-center
      survey on 588 women with pregestational diabetes who delivered a singleton
      pregnancy between 2001 and 2004. Logistic regression was used to obtain crude and
      adjusted estimates of association. RESULTS Preconception counseling was
      associated with better glycemic control 3 months preconception (odds ratio 1.91,
      95% CI 1.10-3.04) and in the first trimester (2.05, 1.39-3.03), higher
      preconception folic acid intake (4.88, 3.26-7.30), and reduced risk of adverse
      pregnancy outcome (P = 0.027). Uptake of preconception counseling was positively
      associated with type 1 diabetes (1.87, 1.14-3.07) and White British ethnicity
      (2.56, 1.17-5.6) and negatively with deprivation score (0.78, 0.70-0.87).
      CONCLUSIONS Efforts are needed to improve preconception counseling rates. Uptake
      is associated with maternal sociodemographic characteristics.

PMID- 20040654
TI  - Use of the site of subcutaneous insulin administration for the measurement of
      glucose in patients with type 1 diabetes.
AB  - OBJECTIVE To simplify and improve the treatment of patients with type 1 diabetes,
      we ascertained whether the site of subcutaneous insulin infusion can be used for
      the measurement of glucose. RESEARCH DESIGN AND METHODS Three special indwelling
      catheters (24-gauge microperfusion [MP] catheters) were inserted into the
      subcutaneous adipose tissue of subjects with type 1 diabetes (n = 10; all C
      peptide negative). One MP catheter was perfused with short-acting insulin (100
      units/ml, Aspart) and used for insulin delivery and simultaneous glucose sampling
      during an overnight fast and after ingestion of a standard glucose load (75 g).
      As controls, the further two MP catheters were perfused with an insulin-free
      solution (5% mannitol) and used for glucose sampling only. Plasma glucose was
      measured frequently at the bedside. RESULTS Insulin delivery with the MP catheter
      was adequate to achieve and maintain normoglycemia during fasting and after
      glucose ingestion. Tissue glucose concentrations derived with the insulin
      perfused catheter agreed well with plasma glucose levels. Median correlation
      coefficient and median absolute relative difference values were found to be 0.93
      (interquartile range 0.91-0.97) and 10.9%, respectively. Error grid analysis
      indicated that the percentage number of tissue values falling in the clinically
      acceptable range is 99.6%. Comparable analysis results were obtained for the two
      mannitol-perfused catheters. CONCLUSIONS Our data suggest that estimation of
      plasma glucose concentrations from the glucose levels directly observed at the
      site of subcutaneous insulin infusion is feasible and its quality is comparable
      to that of estimating plasma glucose concentrations from glucose levels measured
      in insulin-unexposed subcutaneous tissue.

PMID- 20040653
TI  - Cardiovascular autonomic neuropathy, HDL cholesterol, and smoking correlate with
      arterial stiffness markers determined 18 years later in type 1 diabetes.
AB  - OBJECTIVE To examine the relationship between cardiovascular autonomic neuropathy
      and pulse waveform analysis (PWA) measures of arterial stiffness in a childhood
      onset type 1 diabetes population. RESEARCH DESIGN AND METHODS Cardiac autonomic
      nerve function was measured in the baseline examination of the Pittsburgh
      Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes
      by heart rate variability (R-R interval) during deep breathing and expressed as
      expiration-to-inspiration (E/I) ratio. Other cardiovascular and diabetes factors
      were also assessed. PWA was performed using SphgymoCor Px on 144 participants at
      the 18-year follow-up examination. Univariate and multivariate analyses for
      associations between baseline nerve function and other cardiovascular and
      diabetes-related factors were performed for augmentation index (AIx),
      augmentation pressure (AP), and subendocardial viability ratio (SEVR), a
      surrogate marker of myocardial perfusion. RESULTS E/I ratio correlated negatively
      with both AIx (r = -0.18, P = 0.03) and AP (r = -0.32, P < 0.001) and positively
      with SEVR (r = 0.47, P < 0.001) univariately. Lower baseline E/I ratio, HDL
      cholesterol, and a history of smoking were associated with higher follow-up (18
      years later) AIx and AP and lower SEVR in multivariate analyses. Higher baseline
      HbA(1) was also associated with higher AP and lower SEVR multivariately.
      CONCLUSIONS Cardiovascular autonomic neuropathy is associated with increased
      arterial stiffness measures and decreased estimated myocardial perfusion in those
      with type 1 diabetes some 18 years later. This association persists after
      adjustment for potential confounders as well as for baseline HbA(1), HDL
      cholesterol, and smoking history, which were also associated with these PWA
      measures.

PMID- 20040655
TI  - Prevalence of type 1 diabetes autoantibodies (GADA, IA2, and IAA) in overweight
      and obese children.
AB  - OBJECTIVE: Little is known about the prevalence of beta-cell autoantibodies in
      children with excess body weight. The prevalence of type 1 diabetes
      autoantibodies and its relation with hyperglycemia was analyzed in 686
      overweight/obese children and adolescents. RESEARCH DESIGN AND METHODS: All
      children underwent an oral glucose tolerance test, and anti-GAD, anti-IA2, and
      anti-IAA autoantibodies were measured. Autoantibody prevalence was evaluated in
      107 normal-weight children for comparison. RESULTS: A single autoantibody was
      present in 2.18% of overweight/obese subjects and 1.86% normal-weight subjects (P
      = NS). Postload glycemia was significantly higher in antibody-positive children
      (133 +/- 69.9 vs. 105.4 +/- 17.7 mg/dl, P < 0.0001) compared with autoantibody
      negative subjects. No difference in autoantibody distribution was seen when our
      cohort was stratified by age, sex, SDS-BMI, pubertal stage, and homeostasis model
      assessment-insulin resistance (HOMA-IR). CONCLUSIONS: The 2.18% prevalence of
      type 1 diabetes autoantibodies is similar to that reported in nonobese children.
      This study provided evidence that excess body weight and insulin resistance do
      not influence autoantibody frequency.

PMID- 20040656
TI  - Secondary failure of metformin monotherapy in clinical practice.
AB  - OBJECTIVE We sought to document the secondary failure rate of metformin
      monotherapy in a clinical practice setting and to explore factors that predict
      therapeutic failure. RESEARCH DESIGN AND METHODS We studied 1,799 type 2 diabetic
      patients who, between 2004 and 2006, lowered their A1C to <7% after initiating
      metformin monotherapy as their first-ever anti-hyperglycemic drug. We examined
      all A1C values recorded through 31 December 2008 (2-5 years of follow-up),
      defining secondary failure as a subsequent A1C > or =7.5% or the addition or
      substitution of another anti-hyperglycemic agent. We used logistic regression to
      identify factors associated with the probability of secondary failure. RESULTS Of
      the 1,799 patients studied, 42% (n = 748) experienced secondary failure; the mean
      failure rate was 17% per year. However, patients who initiated metformin within 3
      months of diabetes diagnosis failed at an age-and A1C-adjusted rate of 12.2%
      (10.5-14.4%) per year, and patients who initiated while A1C was <7% failed at an
      adjusted rate of 12.3% per year. An interaction term between duration of
      diagnosed diabetes and A1C was not significant. Age, duration, and A1C at
      initiation were the only factors that predicted secondary failure. CONCLUSIONS
      Although metformin failure may occur more rapidly in clinical practice than in
      clinical trails, initiating it soon after diabetes diagnosis and while A1C is low
      might preserve beta-cell function, prolong the effectiveness of metformin, reduce
      lifetime glycemic burden, and prevent diabetes complications. Our findings
      support the current treatment algorithm for hyperglycemia management that
      recommends metformin initiation when diabetes is first diagnosed.

PMID- 20040657
TI  - Prevalence and timing of postpartum glucose testing and sustained glucose
      dysregulation after gestational diabetes mellitus.
AB  - OBJECTIVE To estimate the prevalence of postpartum glucose testing within 6
      months of pregnancies complicated by gestational diabetes mellitus (GDM), assess
      factors associated with testing and timing of testing after delivery, and report
      the test results among tested women. RESEARCH DESIGN AND METHODS This was a
      retrospective study of 11,825 women who were identified as having GDM using the
      100-g oral glucose tolerance test (OGTT) from 1999 to 2006. Postpartum testing
      (75-g 2-h OGTT or fasting plasma glucose [FPG]) within 6 months of delivery and
      test results from laboratory databases are reported. Postpartum test results are
      categorized as normal, impaired fasting glucose (IFG) and/or impaired glucose
      tolerance (IGT), and provisionally diabetic. RESULTS About half (n = 5,939) the
      women were tested with either a FPG or 75-g OGTT from 7 days to 6 months
      postpartum. Of these women, 46% were tested during the 6- to 12-week postpartum
      period. Odds of testing were independently associated with age, race/ethnicity,
      household income, education, foreign-born status, parity, mode of delivery,
      having a postpartum visit, having GDM coded at discharge, and pharmacotherapy for
      GDM. Of the 5,857 women with test results, 16.3% (n = 956) had IFG/IGT and 1.1%
      (n = 66) had provisional diabetes. After adjustment for demographic and clinical
      factors, abnormal postpartum test results was associated with having required
      insulin, glyburide, or metformin during pregnancy and with longer period from
      delivery to postpartum testing. CONCLUSIONS After a pregnancy complicated by GDM,
      automated orders for postpartum testing with notification to physicians and
      electronically generated telephone and e-mail reminder messages to patients may
      improve the rates of postpartum testing for persistence of glucose intolerance.

PMID- 20040658
TI  - Hyperglycemia during total parenteral nutrition: an important marker of poor
      outcome and mortality in hospitalized patients.
AB  - OBJECTIVE: To determine the effect of total parenteral nutrition (TPN)-induced
      hyperglycemia on hospital outcome. RESEARCH DESIGN AND METHODS: The study
      determined whether blood glucose values before, within 24 h, and during days 2-10
      of TPN are predictive of hospital complications and mortality. RESULTS: Subjects
      included a total of 276 patients receiving TPN for a mean duration of 15 +/- 24
      days (+/-SD). In multiple regression models adjusted for age, sex, and diabetes
      status, mortality was independently predicted by pre-TPN blood glucose of 121-150
      mg/dl (odds ratio [OR] 2.2, 95% CI 1.1-4.4, P = 0.030), 151-180 mg/dl (3.41, 1.3
      8.7, P = 0.01), and >180 mg/dl (2.2, 0.9-5.2, P = 0.077) and by blood glucose
      within 24 h of >180 mg/dl (2.8, 1.2-6.8, P = 0.020). A blood glucose within 24 h
      of >180 mg/dl was associated with increased risk of pneumonia (OR 3.1, 95% CI 1.4
      7.1) and acute renal failure (2.3, 1.1-5.0). CONCLUSIONS: Hyperglycemia is
      associated with increased hospital complications and mortality in patients
      receiving TPN.

PMID- 20040659
TI  - Aspects of insulin treatment.

PMID- 20040660
TI  - Delay in diagnosis of diabetes is not the patient's fault.

PMID- 20040661
TI  - Adiponectin and lipoprotein particle size: response to Weiss et Al.

PMID- 20040663
TI  - Plasma 25-hydroxyvitamin d concentration and metabolic syndrome among middle-aged
      and elderly chinese individuals: response to Lu et al.

PMID- 20040665
TI  - Hypoglycemia unawareness is associated with reduced adherence to therapeutic
      decisions in patients with type 1 diabetes: evidence from a clinical audit:
      response to Smith et al.

PMID- 20040667
TI  - High baseline vitamin C levels do not prevent a positive outcome of a lifestyle
      intervention: response to Thamer et al.

PMID- 20040669
TI  - Sexual dysfunction in women with type 1 diabetes: long-term findings from the
      DCCT/EDIC study cohort: response to Enzlin et al.

PMID- 20040670
TI  - Unbalanced M1/M2 phenotype of peripheral blood monocytes in obese diabetic
      patients: effect of pioglitazone.

PMID- 20040671
TI  - Effects of Qigong on glucose control in type 2 diabetes: a randomized controlled
      pilot study.

PMID- 20040672
TI  - Computer and internet use of urban african americans with type 2 diabetes in
      relation to glycemic control, emergency department use, diabetes-related
      knowledge, and health literacy.

PMID- 20040673
TI  - Incidence of treatment for end-stage renal disease among individuals with
      diabetes in the U.S. continues to decline.
AB  - OBJECTIVE: We examined trends in incidence of treatment for diabetes-related end
      stage renal disease (ESRD) in the U.S. RESEARCH DESIGN AND METHODS: Using the
      U.S. Renal Data System, we obtained the number of individuals having diabetes
      listed as primary diagnosis who initiated ESRD treatment between 1990 and 2006.
      Incidence was calculated using the estimated U.S. population with diabetes from
      the National Health Interview Survey and then was age adjusted based on the 2000
      U.S. standard population. Trends were analyzed using joinpoint regression.
      RESULTS: The number of individuals who began diabetes-related ESRD treatment
      increased from 17,727 in 1990 to 48,215 in 2006. From 1990 to 1996, the age
      adjusted diabetes-related ESRD incidence increased somewhat from 299.0 to 343.2
      per 100,000 diabetic population (P = 0.45). However, from 1996 to 2006, the age
      adjusted diabetes-related ESRD incidence decreased by 3.9% per year (P < 0.01)
      from 343.2 to 197.7 per 100,000 diabetic population. Among individuals with
      diabetes aged <45 years, diabetes-related ESRD incidence decreased by 4.3% per
      year (P < 0.01) from 1990 to 2006. Among older individuals, incidence increased
      during the 1990s but decreased in later years, by 3.9% per year (P < 0.01) among
      individuals aged 45-64, by 3.4% per year (P < 0.01) among individuals aged 65-74
      years, and by 2.1% per year (P = 0.02) among individuals aged > or =75 years.
      CONCLUSIONS: Diabetes-related ESRD incidence in the diabetic population has
      declined in all age-groups, probably because of a reduction in the prevalence of
      ESRD risk factors, improved treatment and care, and other factors.

PMID- 20040674
TI  - Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy.
AB  - OBJECTIVE: Our goal was to ascertain the prevalence of pruritus in diabetic and
      nondiabetic subjects and the relevance of symptoms, signs, and nerve functions of
      diabetic polyneuropathy (DPN) of pruritus. RESEARCH DESIGN AND METHODS: A large
      scale survey of 2,656 diabetic outpatients and 499 nondiabetic subjects was
      performed. In diabetic subjects, the relationship between pruritus and age, sex,
      diabetic duration, A1C, Achilles tendon reflex (ATR), and abnormal sensation in
      legs was evaluated. In 105 diabetic subjects, nerve conduction studies,
      quantitative vibratory threshold (QVT), heart rate variability, and a fall of
      systolic blood pressure at a head-up tilt test (DeltaBP) were performed, and the
      relationships between pruritus and nerve functions were evaluated. RESULTS:
      Although the prevalence of truncal pruritus of unknown origin (TPUO) in diabetic
      subjects was significantly higher than that in age-matched nondiabetic subjects
      (11.3 vs. 2.9%, P = 0.0001), the prevalence of other pruritus was not different
      between the two groups. Multiple logistic regression analysis revealed that
      abnormal sensation and ATR areflexia were independent risk factors for TPUO in
      age, sex, duration of diabetes, and A1C. DeltaBP in diabetic subjects with TPUO
      was significantly impaired compared with that in those without TPUO. Larger
      DeltaBP was identified as a significant risk factor of TPUO independent of other
      nerve dysfunctions by multiple logistic regression analysis. CONCLUSIONS: TPUO is
      significantly more frequent in diabetic than in nondiabetic individuals. TPUO is
      significantly associated with symptoms and signs of DPN, including impaired blood
      pressure response in a head-up tilt test. TPUO, therefore, might be a newly
      recognized symptom of DPN.

PMID- 20040675
TI  - Altered C-fiber function as an indicator of early peripheral neuropathy in
      individuals with impaired glucose tolerance.
AB  - OBJECTIVE: This study explored the importance of glycemic burden compared with
      features of the metabolic syndrome in the pathogenesis of diabetic neuropathy by
      comparing C-fiber function in people with type 1 diabetes to that in people with
      impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: The axon reflex
      elicited flare areas (LDIflares) were measured with a laser Doppler imager (LDI)
      in age-, height-, and BMI-matched groups with IGT (n = 14) and type 1 diabetes (n
      = 16) and in healthy control subjects (n = 16). RESULTS: The flare area was
      reduced in the IGT group compared with the control (2.78 +/- 1.1 vs. 5.23 +/- 1.7
      cm(2), P = 0.0001) and type 1 diabetic (5.16 +/- 2.3 cm(2), P = 0.002) groups,
      whereas the flare area was similar in the type 1 diabetic and control groups.
      CONCLUSIONS: This technique suggests that small-fiber neuropathy is a feature of
      IGT. The absence of similar small-fiber neuropathy in those with longstanding
      type 1 diabetes suggests that glycemia may not be the major determinant of small
      fiber neuropathy in IGT.

PMID- 20040676
TI  - Insulin assay standardization: leading to measures of insulin sensitivity and
      secretion for practical clinical care.

PMID- 20040677
TI  - Neuropathy of impaired glucose tolerance and its measurement.

PMID- 20040678
TI  - Barely scratching the surface.

PMID- 20040679
TI  - Overweight in older children and adolescents: treatment or prevention?

PMID- 20040680
TI  - Family history and adoption in the UK: conflicts of interest in medical
      disclosure.

PMID- 20040682
TI  - Ten year secular declines in the cardiorespiratory fitness of affluent English
      children are largely independent of changes in body mass index.
AB  - Secular changes in body mass index (BMI) and cardiorespiratory fitness (20 m
      shuttle-run test performance) were assessed in 10-year-old children from an
      affluent area of England in 1998 (n = 303; 158 boys and 145 girls) and 2008 (n =
      315; 158 boys and 157 girls). Girls' BMI did not change over the 10 year period.
      There was a significant increase in boys' BMI (p = 0.02). Cardiorespiratory
      fitness declined significantly (p<0.001) in both boys (7%) and girls (9%). This
      study shows a large and worrying decline in cardiorespiratory fitness in children
      from an affluent area of England.

PMID- 20040684
TI  - Retraction.

PMID- 20040683
TI  - Nasal bleeding and non-accidental injury in an infant.
AB  - Bleeding from the nose has been a point of controversy in the field of child
      protection in the UK in recent years. Epistaxis in childhood is common but is
      unusual in the first year of life. Oronasal blood in infancy has been proposed as
      a marker of child abuse in this age group, but despite this widely held belief,
      there is a lack of published evidence in this area. The case is reported of an
      infant who presented at one month of age with serious inflicted injuries, who had
      been seen in the emergency department only 13 days previously with a
      "spontaneous" self-limiting nose bleed.

PMID- 20040686
TI  - Understanding emotional abuse.
AB  - Emotional abuse lacks the public and political profile of physical and sexual
      abuse, despite being at their core and frequently their most damaging dimension.
      Difficulties in recognition, definition and legal proof put children at risk of
      remaining in damaging circumstances. Assessment of the emotional environment is
      necessary when interpreting possible physical or sexual abuse and balancing the
      risks and benefits of intervention. This article considers factors contributing
      to professional difficulty. It is suggested that understanding emotional abuse
      from the first principles of the causes and implications of the dysfunctional
      parent-child relationships it represents can help prevention, recognition and
      timely intervention. It may facilitate the professional communication needed to
      build up a picture of emotional abuse and of the emotional context of physical
      and sexual abuse. Doing so may contribute to the safety of child protection
      practice. The long-term cost of emotional abuse for individuals and society
      should be a powerful incentive for ensuring that development of services and
      clinical research are priorities, and that the false economy of short-term saving
      is avoided.

PMID- 20040687
TI  - Question 1: is room air better than 100% oxygen for the resuscitation of the
      depressed full-term newborn?

PMID- 20040689
TI  - Question 2: do caesarean sections reduce the maternal-fetal transmission rate of
      human papillomavirus infection?

PMID- 20040690
TI  - Question 3: can pneumonia caused by penicillin-resistant Streptococcus pneumoniae
      be treated with penicillin?

PMID- 20040692
TI  - Retraction. Quantification of mitochondrial DNA with the A1555G mutation in deaf
      patients using real time-amplification refractory mutation system-quantitative
      PCR.

PMID- 20040695
TI  - Signaling and biological effects of glucagon-like peptide 1 on the
      differentiation of mesenchymal stem cells from human bone marrow.
AB  - Glucagon-like peptide 1 (GLP-1) functions as an incretin hormone with
      antidiabetogenic properties. However, the role of GLP-1 in human bone marrow
      derived mesenchymal stem cells (hMSCs), if any, remains unknown. The effects of
      GLP-1 on hMSCs were tested with regard to cell proliferation, cytoprotection, and
      cell differentiation into adipocytes. The signaling pathways involved in these
      processes were also analyzed. Cells were characterized with biochemical and
      morphological approaches before and after being induced to differentiate into
      adipocytes. PCNA protein levels were used as a proliferation index, whereas cell
      apoptosis was studied by deprivation of fetal bovine serum. Isolated hMSCs
      expressed stem cell markers as well as mRNA and GLP-1 receptor protein. GLP-1
      increased the proliferation of hMSCs, which decreased when they were induced to
      differentiate into adipocytes. This process produced biochemical and
      morphological changes in cells expressing PPARgamma, C/EBPbeta, AP2, and LPL in a
      time-dependent pattern. Notably, GLP-1 significantly reduced the expression of
      PPARgamma, C/EBPbeta, and LPL. These effects were exerted at least through the
      MEK and PKC signaling pathways. In addition, GLP-1 significantly reduced cell
      apoptosis. Our data indicate that, in hMSCs, GLP-1 promotes cellular
      proliferation and cytoprotection and prevents cell differentiation into
      adipocytes. These latter findings underscore the potential therapeutic role of
      GLP-1 in preventing the adipocyte hyperplasia associated with obesity and,
      additionally, could bolster the maintenance of hMSC stores by promoting the
      proliferation and cytoprotection of undifferentiated hMSC.

PMID- 20040693
TI  - Multiple pathways ensure retinoid delivery to milk: studies in genetically
      modified mice.
AB  - Retinoids are absolutely required for normal growth and development during the
      postnatal period. We studied the delivery of retinoids to milk, availing of mouse
      models modified for proteins thought to be essential for this process. Milk
      retinyl esters were markedly altered in mice lacking the enzyme lecithin:retinol
      acyltransferase (Lrat(-/-)), indicating that this enzyme is normally responsible
      for the majority of retinyl esters incorporated into milk and not an acyl-CoA
      dependent enzyme, as proposed in the literature. Unlike wild-type milk, much of
      the retinoid in Lrat(-/-) milk is unesterified retinol, not retinyl ester. The
      composition of the residual retinyl ester present in Lrat(-/-) milk was altered
      from predominantly retinyl palmitate and stearate to retinyl oleate and medium
      chain retinyl esters. This was accompanied by increased palmitate and decreased
      oleate in Lrat(-/-) milk triglycerides. In other studies, we investigated the
      role of retinol-binding protein in retinoid delivery for milk formation. We found
      that Rbp(-/-) mice maintain milk retinoid concentrations similar to those in
      matched wild-type mice. This appears to arise due to greater postprandial
      delivery of retinoid, a lipoprotein lipase (LPL)-dependent pathway. Importantly,
      LPL also acts to assure delivery of long-chain fatty acids (LCFA) to milk. The
      fatty acid transporter CD36 also facilitated LCFA but not retinoid incorporation
      into milk. Our data show that compensatory pathways for the delivery of retinoids
      ensure their optimal delivery and that LRAT is the most important enzyme for milk
      retinyl ester formation.

PMID- 20040696
TI  - Lofexidine, an {alpha}2-receptor agonist for opioid detoxification.
AB  - OBJECTIVE: To review the pharmacology, toxicology, pharmacokinetics, efficacy,
      adverse effects, drug interactions, and dosage guidelines for lofexidine, an
      alpha(2)-agonist, for opioid detoxification. DATA SOURCES: Primary literature was
      identified through a MEDLINE search (1950-September 2009), EMBASE (1988-July
      2009), International Pharmaceutical Abstracts (1970-September 2009), and the
      Cochrane Library (1996-September 2009) using the key words lofexidine and opioid
      withdrawal. Abstracts were included in the absence of published results of
      studies. STUDY SELECTION AND DATA EXTRACTION: Studies published in English
      language literature reporting on animal and human pharmacology, toxicology, and
      pharmacokinetics were included in addition to clinical trials using lofexidine
      for opioid detoxification in comparison to placebo or active controls. DATA
      SYNTHESIS: Lofexidine is an alpha(2)-agonist structurally related to clonidine.
      It is not an effective antihypertensive agent; however, it decreases the
      sympathetic outflow responsible for many opioid withdrawal symptoms. Nine
      clinical studies were reviewed representing 354 patients receiving lofexidine
      including a recent Phase 3 clinical trial. Eight studies involved comparisons of
      lofexidine to an opioid receptor agonist or clonidine for opioid detoxification.
      In these trials, lofexidine dosing was titrated to a maximum of 1.6-3.2 mg/day in
      divided doses for a total of 5-18 days. The data suggest that lofexidine has
      positive efficacy in reducing opioid withdrawal symptoms and is at least as
      effective as the opioid receptor agonists utilized for detoxification. Not all
      withdrawal symptoms are alleviated by alpha(2)-agonists, with many patients
      complaining of insomnia and aching. The most common adverse event with lofexidine
      in the Phase 3 trial was insomnia. Hypotension was also reported; however, the
      studies comparing clonidine with lofexidine suggest decreased incidence and
      severity of adverse events with lofexidine. CONCLUSIONS: Lofexidine appears to be
      a promising agent for opioid detoxification. If approved, it would be the first
      nonopioid agent approved for this indication. Further large-scale controlled
      studies are needed to identify the safest, most effective dosage regimen required
      to achieve opioid detoxification.

PMID- 20040697
TI  - Evaluation of pharmacy-implemented medication reconciliation directed at
      antiretroviral therapy in hospitalized HIV/AIDS patients.

PMID- 20040698
TI  - Black box warning contraindicated comedications: concordance among three major
      drug interaction screening programs.
AB  - BACKGROUND: Black box warnings represent the strongest safety warning that the
      Food and Drug Administration can issue for a marketed prescription drug. Some
      black box warnings recommend against coadministration of specific medications due
      to an increased risk for serious, perhaps life-threatening, effects. OBJECTIVE:
      To determine the level of agreement in presence, clinical severity scores level
      of documentation ratings, and alert content among 3 leading drug interaction
      screening programs with regard to contraindicated comedications that are
      mentioned in black box warnings. METHODS: We reviewed the prescribing information
      for currently marketed prescription drugs with a black box warning that mentioned
      a contraindicated drug combination. We selected the drug interaction databases
      Facts & Comparisons 4.0, MICROMEDEX DRUG-REAX, and Lexi-Comp Lexi-Interact to
      evaluate the interactions. Discrepancies in the inclusion of interactions and
      level of agreement in clinical severity scores and level of documentation ratings
      for each interaction were assessed, using descriptive statistics, Spearman's
      correlation coefficient, Kendall-Stuart tau-c, and Cronbach's alpha. RESULTS: We
      identified 11 drugs with black box warnings that contained information on 59
      unique contraindicated drug combinations, only 68% of which were covered by any
      source. Lexi-Comp detected the most interactions (n = 29) and DRUG-REAX the least
      (n = 18). Only 3 drug combinations were detected and rated as contraindicated or
      potentially life-threatening in all 3 databases. The severity scores and level of
      documentation ratings varied widely. CONCLUSIONS: There are discrepancies among
      major drug interaction screening programs in the inclusion, severity, and level
      of documentation of contraindicated drug combinations mentioned in black box
      warnings. Further studies could explore the implications of these
      inconsistencies, particularly with regard to the integration of black box warning
      information in clinical practice. Clinicians should consult multiple drug
      resources to maximize the potential for detecting a potentially severe drug
      interaction.

PMID- 20040699
TI  - INR elevation with maitake extract in combination with warfarin.

PMID- 20040700
TI  - Raltegravir-based HAART regimen in a patient with large B-cell lymphoma.
AB  - OBJECTIVE: To describe the antiretroviral management of a patient diagnosed
      simultaneously with HIV/AIDS and diffuse large B-cell lymphoma, focusing on the
      drug-drug interactions between highly active antiretroviral therapy (HAART) and
      concomitant cancer chemotherapy. CASE SUMMARY: A 55-year-old white man was
      recently diagnosed with HIV/AIDS and presented 1 month later with complaints of
      nausea, vomiting, abdominal pain, double vision, right eye discomfort/swelling,
      and a 3.6-kg weight loss. An excisional biopsy of a right inguinal lymph node
      confirmed a new diagnosis of diffuse large B-cell lymphoma. HAART and a
      chemotherapeutic regimen, including cyclophosphamide, doxorubicin, vincristine,
      prednisone (CHOP) with intrathecal methotrexate, was to be initiated. As the
      potential for multiple drug-drug interactions existed, raltegravir, abacavir, and
      lamivudine were chosen for the initial HAART regimen. The patient achieved and
      maintained an undetectable viral load throughout 6 CHOP cycles. DISCUSSION: HAART
      improves the chemotherapeutic response in patients with HIV and lymphoma.
      Multiple drug-drug interactions are possible in patients who are to receive CHOP
      and HAART. Cyclophosphamide and vincristine are metabolized via the CYP3A4
      isoenzyme. Protease inhibitors (PIs) and nonnucleoside reverse transcriptase
      inhibitors both inhibit and induce CYP3A4, with the potential for altered
      chemotherapeutic and cytotoxic effects. When PIs are combined with CHOP,
      mortality is reduced, but increased adverse effects are demonstrated.
      Raltegravir, an integrase inhibitor, is eliminated via glucuronidation and
      results in minimal drug-drug interactions. Raltegravir improves virologic and
      immunologic responses in HAART-naive patients and thus would be a suitable
      alternative for preventing chemotherapeutic-HAART interactions. CONCLUSIONS:
      There is limited information published regarding the potential for interactions
      between HAART and cancer chemotherapy. While further research is necessary, it is
      important for clinicians to consider the potential for drug-drug interactions
      when designing a HAART regimen concurrently with chemotherapy.

PMID- 20040701
TI  - Fluconazole prophylaxis in high-risk neonates.
AB  - OBJECTIVE: To evaluate the literature regarding the use of fluconazole
      prophylaxis in high-risk neonates. DATA SOURCES: Literature was accessed through
      MEDLINE (February 2001-August 2009) using the search terms fluconazole and
      prophylaxis, with limits for age group (ie, birth-18 y). Reference citations from
      identified articles were also reviewed. DATA SELECTION AND DATA EXTRACTION: All
      prospective and retrospective studies in English identified from MEDLINE were
      evaluated. DATA SYNTHESIS: Critically ill neonates possess a number of risk
      factors that predispose them to fungal colonization with Candida spp. In many
      cases, colonization may progress to invasive systemic infections despite efforts
      aimed at early diagnosis and treatment. Because of its success among
      immunocompromised patients, fluconazole prophylaxis has been suggested as a
      possible approach for reducing the rates of both colonization and invasive fungal
      infections among at-risk neonates. To date, 4 prospective randomized controlled
      trials and 8 retrospective cohort studies have examined fluconazole prophylaxis
      in neonates. Although fluconazole prophylaxis appears to reduce the rates of
      colonization and invasive fungal infections, no trial in this review was able to
      demonstrate a significant difference in long-term morbidity or mortality.
      Concerns also remain regarding the adverse effects associated with prolonged
      exposure to fluconazole therapy. Lack of standardized study designs and treatment
      regimens also limit widespread recommendation for the use of fluconazole
      prophylaxis in clinical practice. CONCLUSIONS: While it may be beneficial for
      critically ill neonates with certain predisposing risk factors (eg, central
      venous access, sustained exposure to broad-spectrum antibiotics, or units with
      significantly high incidence of invasive fungal infections), existing research
      does not support the use of fluconazole prophylaxis based on birth weight or
      gestational age alone. Multifactor analysis evaluating the effect of fluconazole
      prophylaxis is necessary to establish which neonates would benefit from this
      practice.

PMID- 20040702
TI  - Integrase inhibitors: a novel class of antiretroviral agents.
AB  - OBJECTIVE: To review the pharmacology, efficacy, safety, and resistance profiles
      of the integrase inhibitors raltegravir and elvitegravir. DATA SOURCES: A search
      of PubMed was conducted (2000-August 2009) using the following key words:
      raltegravir, MK-0518, elvitegravir, and GS-9137. Articles were evaluated for
      content and bibliographies were reviewed. Data available exclusively in abstracts
      from major infectious diseases and HIV conferences were also evaluated for
      inclusion. STUDY SELECTION AND DATA EXTRACTION: Studies included were in vitro
      investigations; Phase 1, 2, and 3 clinical trials; retrospective analyses
      including case reports; and pharmacokinetic and pharmacodynamic evaluations. DATA
      SYNTHESIS: Raltegravir is currently approved by the Food and Drug Administration
      for the management of HIV-1 infection in treatment-naive or-experienced adults as
      part of an optimized combination regimen. When combined with other active agents,
      it has demonstrated similar virologic efficacy after 96 weeks to the combination
      of efavirenz, tenofovir, and emtricitabine in treatment-naive patients. Unlike
      many antiretrovirals, raltegravir does not enter cytochrome P450 metabolism and
      instead undergoes glucuronidation. Elvitegravir is in the late stages of clinical
      development. A Phase 2 study has demonstrated virologic efficacy in treatment
      experienced patients comparable to protease inhibitor-based regimens after 24
      weeks. Boosting of elvitegravir through inhibition of CYP3A4 metabolism has been
      investigated and suggests a pharmacokinetic profile conducive to once-daily
      dosing. Phase 2 and 3 clinical trials evaluating boosted elvitegravir are in
      process. The Phase 2 trial combines elvitegravir with a non-ritonavir boosting
      agent plus tenofovir/emtricitabine given once daily as a "quad-pill" formulation.
      The Phase 3 trial compares once-daily ritonavir-boosted elvitegravir with twice
      daily raltegravir, each given with an optimized background regimen. Both
      integrase inhibitors are well tolerated and raltegravir has few drug-drug
      interactions. Resistance mutations have been identified in patients experiencing
      virologic failure and cross resistance between raltegravir and elvitegravir has
      been confirmed. CONCLUSIONS: The integrase inhibitors provide a novel target for
      antiretroviral therapy and provide an option for patients harboring resistance to
      other antiretrovirals.

PMID- 20040703
TI  - Safety considerations and potential interactions of vitamins: should vitamins be
      considered drugs?
AB  - OBJECTIVE: To examine adverse effects, adverse events, and potential interactions
      of vitamins in light of their current prevalence of use, and to discuss whether
      vitamins should be considered over-the-counter drugs or natural health
      products/dietary supplements. DATA SOURCES: We performed a MEDLINE/PubMed search,
      explored 4 online databases (Medline Plus, Drug Digest, Natural Medicine
      Comprehensive Database, and the database of the University of Maryland), and
      examined reference lists of included studies published from 1966 through October
      2009. STUDY SELECTION AND DATA EXTRACTION: The studies were reviewed, with an
      emphasis on randomized controlled clinical trials. We included articles with the
      most clinically important information with regard to adverse events and
      interactions. DATA SYNTHESIS: Vitamins are used by over one third of the North
      American population. Vitamins have documented adverse effects and toxicities, and
      most have documented interactions with drugs. While some vitamins (biotin,
      pantothenic acid, riboflavin, thiamine, vitamin B(12), vitamin K) have minor and
      reversible adverse effects, others, such as fat-soluble vitamins (A, E, D), can
      cause serious adverse events. Two water-soluble vitamins, folic acid and niacin,
      can also have significant toxicities and adverse events. CONCLUSIONS: Our
      recommendation is that vitamins A, E, D, folic acid, and niacin should be
      categorized as over-the-counter medications. Labeling of vitamins, especially
      those intended for children and other vulnerable groups, should include
      information on possible toxicities, dosing, recommended upper intake limits, and
      concurrent use with other products. Vitamin A should be excluded from
      multivitamin supplements and food fortificants.

PMID- 20040704
TI  - Impact of a pharmaceutical care intervention on blood pressure control in a chain
      pharmacy practice.
AB  - BACKGROUND: Hypertension affects over 50 million Americans, with only 50% of
      patients being adequately controlled. Several pharmacist counseling and
      pharmacist-physician comanagement studies have documented that community
      pharmacist interventions improve blood pressure (BP) management. OBJECTIVE: To
      determine whether community pharmacists can improve clinical endpoints including
      hypertension control, drug therapy dosing, adherence to prescribed regimens,
      adverse drug reaction incidence, patient understanding, response to therapy, and
      quality-of-life. METHODS: The program included the education and training of a
      group of 18 chain community pharmacists in hypertension therapies, monitoring,
      and management. Protocols and documentation tools were based on nationally
      accepted clinical practice guidelines for hypertension in place at the time of
      the study. Pharmaceutical care (PC) was then compared with usual care (UC) over a
      12-month period. RESULTS: The study initially enrolled 180 PC and 196 UC
      patients, with 44% (PC) and 32% (UC) of the patients reporting a final BP
      measurement. A larger proportion (50%) of PC patients who had poorly controlled
      hypertension at baseline (>140/90 mm Hg) were controlled compared with UC
      patients (22%). The average reduction in systolic BP was 9.9 mm Hg in PC patients
      compared with 2.8 mm Hg in UC patients (p < 0.05). Changes in diastolic BP were
      similar in the PC and UC groups. Based on patient self-report, PC patients were
      more likely to say that they take their medicines as prescribed compared with UC
      patients (p < 0.05). The 1- to 6-month antihypertensive adherence rate was higher
      in PC patients (0.91 +/- 0.15) compared to UC patients (0.78 +/- 0.30) (p =
      0.02); there was no significant difference in adherence rate during the 7- to 12
      month period. CONCLUSIONS: Community pharmacists can positively affect patient
      medication adherence during the 6-month period following counseling by a
      pharmacist along with an improvement in patient BP. However, there is much room
      for improvement in PC programs and in the number of patients who properly adhere
      to their medications.

PMID- 20040705
TI  - Integrating type 2 diabetes mellitus and depression treatment among African
      Americans: a randomized controlled pilot trial.
AB  - PURPOSE: The purpose of this study was to examine whether integrating depression
      treatment into care for type 2 diabetes mellitus among older African Americans
      improved medication adherence, glycemic control, and depression outcomes.
      METHODS: Older African Americans prescribed pharmacotherapy for type 2 diabetes
      mellitus and depression from physicians at a large primary care practice in west
      Philadelphia were randomly assigned to an integrated care intervention or usual
      care. Adherence was assessed at baseline, 2, 4, and 6 weeks using the Medication
      Event Monitoring System to assess adherence. Outcomes assessed at baseline and 12
      weeks included standard laboratory tests to measure glycemic control and the
      Center for Epidemiologic Studies Depression Scale (CES-D) to assess depression.
      RESULTS: In all, 58 participants aged 50 to 80 years participated. The proportion
      of participants who had 80% or greater adherence to an oral hypoglycemic
      (intervention 62.1% vs usual care 24.1%) and an antidepressant (intervention
      62.1% vs usual care 10.3%) was greater in the intervention group in comparison
      with the usual care group at 6 weeks. Participants in the integrated care
      intervention had lower levels of glycosylated hemoglobin (intervention 6.7% vs
      usual care 7.9%) and fewer depressive symptoms (CES-D mean scores: intervention
      9.6 vs usual care 16.6) compared with participants in the usual care group at 12
      weeks. CONCLUSION: A pilot randomized controlled trial integrating type 2
      diabetes mellitus treatment and depression was successful in improving outcomes
      among older African Americans. Integrated interventions may be more feasible and
      effective in real-world practices with competing demands for limited resources.

PMID- 20040706
TI  - Self-esteem in pure bullies and bully/victims: a longitudinal analysis.
AB  - Past research on the self-esteem of bullies has produced equivocal results.
      Recent studies have suggested that the inconsistent findings may be due, in part,
      to the failure to account for bully/victims: those children who both bully and
      are victims of bullying. In this longitudinal study, we examined the distinctions
      among pure bullies, pure victims, bully/victims, and noninvolved children in a
      sample of 307 middle school students. Analyses of cross-sectional and
      longitudinal results supported the importance of distinguishing between pure
      bullies and bully/victims. In addition, results revealed some interesting sex
      differences: girls in the pure bully and bully/victim groups reported significant
      increases in self-esteem over time, with girls in the pure bully group reporting
      the greatest increase, whereas boys in these groups reported no significant
      changes in self-esteem over time.

PMID- 20040707
TI  - Individual and relationship factors that differentiate female offenders with and
      without a sexual abuse history.
AB  - The link between prior sexual abuse and female offending is one of the most
      consistent findings within the etiology of female offending. It is not, however,
      part of every female offender's life history. Working from research on the impact
      of abuse on individuals, the current article examines the individual and
      relationship factors that differentiate female offenders (n = 131) with a history
      of sexual abuse and female offenders without a history of sexual abuse. Results
      from chi-square, t test, and logistic regression analyses indicated that
      offenders with a history of sexual abuse were more likely to report their
      household as loving, were more deeply involved in the criminal justice system,
      had more difficulty staying employed, and were more likely to be involved in an
      abusive relationship. Implications of the results are discussed.

PMID- 20040708
TI  - Bounded rationality, retaliation, and the spread of urban violence.
AB  - Drawing from in-depth interviews with 52 active street criminals, this article
      examines the grounded theoretic implications of bounded rationality for
      retaliatory street violence. The bounds on rationality that this article explores
      are anger, uncertainty, and time pressure. These bounds create imperfections in
      the retaliatory decision-making process that, in turn, cause asymmetries in the
      way that reprisal is enacted. Two asymmetries are operative in this regard:
      strike intensity and target choice. Anger produces asymmetries of both types.
      Uncertainty and time pressure produce only target-choice asymmetry. All three
      modalities cause retaliation to be redirected. Redirection promotes the spread of
      urban violence through conflict spirals.

PMID- 20040709
TI  - Computerized aid improves safety decision process for survivors of intimate
      partner violence.
AB  - A computerized safety decision aid was developed and tested with Spanish or
      English-speaking abused women in shelters or domestic violence (DV) support
      groups (n = 90). The decision aid provides feedback about risk for lethal
      violence, options for safety, assistance with setting priorities for safety, and
      a safety plan personalized to the user. Women reported that the decision aid was
      useful and provided much-needed privacy for making safety decisions. The majority
      (69%) reported severe to extreme danger in their relationship as scored by Danger
      Assessment (DA); only 60% reported having made a safety plan. After using the
      safety decision aid, the women felt more supported in their decision (p = .012)
      and had less total decisional conflict (p = .014). The study demonstrated that a
      computerized safety decision aid improved the safety planning process, as
      demonstrated by reduced decisional conflict after only one use in a sample of
      abused women.

PMID- 20040710
TI  - Family conflict and childhood aggression: the role of child anxiety.
AB  - Family conflict and childhood anxiety has been implicated in the development of
      aggressive behaviors, but the nature of these relationships has not been fully
      explored. Thus, the present study examined the role of anxiety in moderating the
      relationship between family conflict and childhood aggression in 50 children aged
      7 to 13 years. Specifically, the study proposed that family conflict would be
      positively related to aggression in the context of higher levels of child
      anxiety. Parents completed self-report instruments examining family conflict and
      aggressive behavior exhibited by their children. Children completed a self-report
      measure of anxiety. The hypothesis was partially supported as family conflict was
      related to increased proactive but not reactive aggression in children with high
      levels of anxiety. Implications of these findings are discussed.

PMID- 20040711
TI  - Coercive sexual experiences, protective behavioral strategies, alcohol
      expectancies and consumption among male and female college students.
AB  - Alcohol use and sexual assault on college campuses are highly prevalent and the
      focus of numerous prevention and intervention efforts. Our goals were to gain a
      greater understanding of the relationship between coercive sexual experiences,
      utilization of protective behavioral strategies and alcohol expectancies and
      consumption among male and female college students. We surveyed 370 college
      students regarding their past year experiences and found that 34% of women and
      31% of men reported unwanted sexual contact, 6% of women and 13% of men reported
      engaging in sexually coercive behavior, and 4% of women and 9% of men reported
      experiencing both unwanted contact and engaging in sexually coercive behavior.
      Findings indicated students who experienced unwanted sexual contact reported
      significant differences in alcohol expectancies. More specifically, those who
      engaged in sexually coercive behaviors had significantly higher sex-related
      alcohol expectancies. In addition, recipients of unwanted contact reported higher
      alcohol consumption, used fewer protective strategies when drinking, and
      experienced more negative consequences due to their alcohol use. Results suggest
      that campus alcohol and sexual assault prevention efforts should include
      information on alcohol expectancies and use of protective strategies.

PMID- 20040712
TI  - An interactional perspective on the relationship of immigration to intimate
      partner violence in a representative sample of help-seeking women.
AB  - This article reports a study of the possible impact of immigration on
      interactional aspects of intimate partner violence (IPV) among help-seeking
      women. Are there differences concerning (a) IPV categories, (b) IPV severity,
      frequency, duration, regularity, and predictability, (c) guilt and shame, (d)
      partners' ethnicity, and (e) children being exposed to interparental IPV,
      adjusted for sociodemographic variables? A representative sample of IPV help
      seeking women (N = 157) recruited from family counseling, police, and shelters in
      Norway were interviewed. Multivariate analyses showed that immigrant women had
      lower income, were less likely to use alcohol and had increased likelihood of
      having an immigrant partner. No differences were found concerning IPV severity,
      frequency, guilt, shame, or victimization pertaining to different IPV categories.
      Immigrant women were better at predicting physical IPV but had an increased risk
      of physical injury related to sexual IPV. Children's risk of being exposed to
      interparental IPV increased if parents were immigrants. Psychosocial consequences
      of being an immigrant such as having a lower sociodemographic rank rather than
      IPV aspects constituted the main difference between ethnic Norwegian and
      immigrant help-seeking women.

PMID- 20040713
TI  - Neighborhood characteristics as predictors of male to female and female to male
      partner violence.
AB  - This article examines the association between neighborhood characteristics at the
      census tract-level, couples' perceived neighborhood social cohesion and informal
      social control, and male-to-female (MFPV) and female-to-male (FMPV) partner
      violence in the United States. Data come from a second wave of interviews (2000)
      with a national sample of couples 18 years of age and older who were first
      interviewed in 1995. The path analysis shows that poverty is associated with
      perceived social cohesion and perceived social control as hypothesized. However,
      there is no significant mediation effect for social control or social cohesion on
      any type of violence. In the path analysis, Black ethnicity is associated with
      social cohesion, which is associated with MFPV. Intimate partner violence (IPV),
      as a form of domestic violence, may not be as concentrated in high-poverty
      neighborhoods as criminal violence. IPV may be more determined by personal and
      dyadic characteristics than criminal violence.

PMID- 20040714
TI  - Risk recognition and intimate partner violence.
AB  - The objective of this study was to determine whether female victims of physical
      forms of intimate partner violence (IPV) displayed deficits in risk recognition,
      or the ability to detect danger, in physically violent dating encounters. A total
      of 182 women watched a video depicting a psychologically and physically
      aggressive encounter between heterosexual dating partners and made repeated
      judgments about the interaction. Results from this study provided evidence for
      the validation of this methodology and found that history of physical forms of
      IPV was associated with risk recognition ability, such that victims of IPV were
      less likely to recognize the danger involved in the video vignette compared to
      nonvictims. Results showed important implications for IPV prevention programs.

PMID- 20040715
TI  - In their own words: sophomore college men describe attitude and behavior changes
      resulting from a rape prevention program 2 years after their participation.
AB  - The study conducted involved assessing students from a Southeastern public
      university during two academic years, after their participation in an all-male
      sexual assault peer education program. The study findings revealed that 79% of
      184 college men reported attitude change, behavior change, or both. Furthermore,
      a multistage inductive analysis revealed that after seeing The Men's Program, men
      intervened to prevent rapes from happening. Participants also modified their
      behavior to avoid committing sexual assault when they or a potential partner were
      under the influence of alcohol. Implications for future research were discussed.

PMID- 20040716
TI  - Traumatic stress symptoms of women exposed to different forms of childhood
      victimization and intimate partner violence.
AB  - Interviews of women with (n = 193) and without (n = 170) recent exposure to
      intimate partner violence (IPV) were used to examine how IPV and past exposure to
      child abuse influence self-reports of posttraumatic stress disorder (PTSD)
      symptoms. The measurement of IPV included assessing psychological, physical,
      escalated physical, and sexual abuse. Women's retrospective accounts of childhood
      victimization included reports of physical abuse, sexual abuse, and witnessing
      domestic violence growing up. Each form of adult IPV showed an independent
      association with PTSD symptoms, as did each form of childhood victimization. In
      regression models including child and adult abuse together, adult IPV and
      childhood sexual abuse were related to PTSD symptoms, and adult IPV mediated the
      association between childhood physical abuse and adult PTSD. Tests of the
      interactions between childhood and adulthood victimization on PTSD symptoms were
      not significant. Findings are discussed within the context of a life-course
      perspective of trauma.

PMID- 20040717
TI  - Links between middle-childhood trajectories of family dysfunction and indirect
      aggression.
AB  - Using data from three waves of a large Canadian data set, this research examined
      the relationship between middle-childhood trajectories of family dysfunction and
      indirect aggression. The authors applied family systems, developmental
      psychopathology, and life-course conceptualizations to meet this objective. The
      data analytic strategy used separate multivariate logits to examine this
      relationship, with and without the extent to which other possible explanations
      (acting as control variables) predict belonging to the highest family dysfunction
      trajectory. These included marital transition, socioeconomic status, family size,
      and depressive symptoms experienced by the adult most knowledgeable about the
      child (mostly mothers). The authors also explored possible interactions between
      indirect aggression and these explanatory variables. Supporting their hypothesis
      for both boys and girls, prolonged-duration high doses of family dysfunction were
      associated with the most extreme developmental trajectories of indirect
      aggression during middle childhood. Results showed gender specificity with
      respect to the influence of the explanatory variables on family dysfunction. For
      girls, the link between family dysfunction and indirect aggression persisted
      above and beyond such contextual influences. For boys, the relationship became
      unimportant once contextual factors were taken into account.

PMID- 20040721
TI  - What have the difference scores not been telling us? A critique of the use of
      self--ideal discrepancy in the assessment of body image and evaluation of an
      alternative data-analytic framework.
AB  - Difference scores are often used as a means of assessing body image satisfaction
      using silhouette scales. Unfortunately, difference scores suffer from numerous
      potential methodological problems, including reduced reliability, ambiguity,
      confounded effects, untested constraints, and dimensional reduction. In this
      article, the methodological problems are outlined and an alternative framework is
      discussed. The alternative consists of a minimum of testing the constraints
      implied by the difference score model, and at most evaluating more exact body
      image hypotheses by incorporating nonlinear terms in a regression and testing
      features of the response surface. Two empirical examples are used to illustrate
      the utility of these methods. The first example uses both polynomial regression
      and response surface methods to examine eating disorder outcomes, whereas the
      second example uses polynomial regression to examine the outcomes related to
      muscle dysmorphia. Directions for future research related to assessment of body
      image are discussed.

PMID- 20040722
TI  - A multitrait--multimethod examination of the reynolds intellectual assessment
      scales in a college sample.
AB  - This study assessed trait validity of the Reynolds Intellectual Assessment
      Scales' (RIAS) Verbal Index (VIX) and Nonverbal Index (NIX) scores in a group of
      college students. Using both observation of patterns and latent variable modeling
      of a multitrait-multimethod correlation/covariance matrix, the results indicate
      that the RIAS VIX scores behaved in a manner predicted from the theory behind
      their construction; namely, they related strongly to other measures of
      crystallized intelligence (Gc) and, together, they formed a salient Gc factor.
      The NIX scores, however, did not behave as predicted-showing as strong, or
      stronger, associations with measures of Gc than measures of fluid intelligence.
      Although more studies of this type are needed across different samples before
      making broad generalizations, the results from the present study support the use
      and interpretation of the RIAS VIX score, but not the NIX score.

PMID- 20040723
TI  - The factor structure and age-related factorial invariance of the Delis-Kaplan
      Executive Function System (D-KEFS).
AB  - There has been an increased interest in the structure of and relations among
      executive functions.The present study examined the factor structure as well as
      age-related factorial invariance of the Delis-Kaplan Executive Function System (D
      KEFS), a widely used inventory aimed at assessing executive functions. Analyses
      were first conducted using data provided in the D-KEFS technical manual and were
      then replicated in an independent sample of male early adolescents aged 11 to 16
      years. Results revealed a three-factor solution best fit the data across groups
      and samples; measurement properties appeared to be invariant across age groups
      for certain loadings and variant for others. The three factors were labeled
      Conceptual Flexibility, Monitoring, and Inhibition. These findings provide better
      understanding of the measurement properties of the D-KEFS and contribute to the
      larger literature on the structure of measures intended to assess executive
      functions.

PMID- 20040724
TI  - Children's attributional style from middle childhood to early adolescence:
      Further validation of the paper-and-pencil versions of the children's
      attributional style interview.
AB  - The psychometric properties of two paper-and-pencil versions of the Children's
      Attributional Style Interview (i.e., CASI-I and CASI-II) were evaluated in a
      sample of 166 third and fourth graders and a sample of 245 sixth and seventh
      graders. The results demonstrated strong internal consistency reliability,
      convergent validity, and a factor structure that was consistent with theory in
      both samples. Furthermore, analyses demonstrated adequate evidence of the
      reliability and validity of several dimensional subscale scores and the composite
      measures of attributional style for both positive and negative events. These
      results suggest the utility of the CASI in research testing specific
      attributional predictions of cognitive theories of depression with the
      dimensional subscale scores. They further add to the literature by demonstrating
      item-level factor analytic support for a children's attributional style measure
      and the feasibility of administration sizes larger than previously tested, which
      add to the utility of the CASI in large-scale research designs.

PMID- 20040725
TI  - Autism spectrum disorders as a qualitatively distinct category from typical
      behavior in a large, clinically ascertained sample.
AB  - The present study evaluated the hypothesis that autism spectrum disorders (ASDs)
      are best represented as a discrete category distinct from typical behavior within
      autism-affected families. The latent structure, categorical versus dimensional,
      of ASDs informs future diagnostic revisions, clinical assessment, and the design
      of future research. Data were obtained from Interactive Autism Network, a
      registry that preferentially recruits families with at least one ASD-affected
      child. Caregivers reported autism symptoms for affected and unaffected children
      using the Social Responsiveness Scale and Social Communication Questionnaire.
      Taxometric and latent variable models examined whether dimensional or categorical
      models best fit the data. Taxometric and latent variable model comparisons
      consistently indicated two-group mixtures for all indicator sets, even in
      participants designated as unaffected by caregivers. The identified category was
      associated with external indicators of disability, supporting its validity.
      Results indicated that ASD is best characterized as a category, distinct from
      typical behavior within ASD-affected families.

PMID- 20040726
TI  - Where do we draw the line? Assigning cases to subsamples for MAMBAC, MAXCOV, and
      MAXEIG taxometric analyses.
AB  - There are several important decisions that must be made when implementing
      taxometric procedures such as mean above minus below a cut (MAMBAC), maximum
      covariance (MAXCOV), and maximum eigenvalue (MAXEIG). A Monte Carlo study was
      performed with 10,000 (5,000 categorical, 5,000 dimensional) samples to examine 5
      ways to locate the first and last MAMBAC cuts and 24 ways to perform MAXCOV and
      MAXEIG. For MAMBAC, there was little difference across conditions, with slightly
      more accurate results obtained when a small, fixed number of cases (n = 10 or 25)
      was located beyond the most extreme cuts. For MAXCOV and MAXEIG, the results were
      more palpable: MAXCOV slightly outperformed MAXEIG, windows achieved
      significantly better results than intervals, and a larger number of cases per
      subsample were associated with more accurate results. Alcohol misuse data
      obtained from a group of male prisoners were used to illustrate relationships
      observed in the Monte Carlo study.

PMID- 20040727
TI  - The validity of the psychopathic personality inventory--revised in a community
      sample.
AB  - Research on the Psychopathic Personality Inventory-Revised (PPI-R) has revealed
      two factors: Fearless Dominance, and Self-Centered Impulsivity. This study
      examined the validity of these PPI-R factors in a community sample (N = 675).
      First, confirmatory factor analyses did not support the two-factor structure.
      Second, the PPI-R factors showed good convergent and discriminant validity with
      two other self-report measures of psychopathy, that is, the Youth Psychopathic
      Traits Inventory and Levenson's Self-Report of Psychopathy. Third, PPI-R factors
      exhibited good external validity in relation to various theoretically relevant
      correlates. The results indicate that the PPI-R factors have good convergent,
      discriminant, and external validity, but confirmatory factor analysis raises
      concerns about the robustness of the two-factor structure.

PMID- 20040729
TI  - Violence risk assessment and facet 4 of the Psychopathy Checklist: predicting
      institutional and community aggression in two forensic samples.
AB  - The Psychopathy Checklist and Psychopathy Checklist-Revised (PCL/PCL-R) were used
      to predict institutional aggression and community violence in two groups of
      forensic patients. Results showed that Facet 4 (Antisocial) of the PCL/PCL-R or
      one of its parcels consistently achieved incremental validity relative to the
      first three facets, whereas the first three facets failed to achieve incremental
      validity relative to Facet 4. One of the two Facet 4 parcels, Parcel G (General
      Acting Out), was the only PCL-R measure to consistently achieve success in
      classifying individual cases using the receiver operating characteristic
      approach. These findings suggest that Facet 4 and its parcels may play a role in
      violence risk assessment, although the generalizability of these findings to
      various forensic settings and contexts requires further study.

PMID- 20040728
TI  - The psychometric properties of the Kentucky Inventory of Mindfulness Skills in
      clinical populations.
AB  - The Kentucky Inventory of Mindfulness Skills (KIMS) is a well-validated
      multidimensional questionnaire measuring dimensions of mindfulness on four
      scales: Observing, Describing, Act With Awareness, and Accept Without Judgment.
      Even though the KIMS has been used in several clinical studies no information is
      available about the psychometric properties in different clinical samples. The
      present study includes two clinical samples: a German sample of people diagnosed
      with borderline personality disorder, posttraumatic stress disorder, or major
      depression and an English sample of people diagnosed with recurrent depression.
      Results of confirmatory factor analysis offer good support for the hypothesized
      model of four correlated factors, whereas the model of one general underlying
      mindfulness factor as a second order construct was not confirmed. Furthermore,
      our analyses revealed that the KIMS scales show high internal consistency and
      that all KIMS scales are sensitive to change in a subsample of participants
      taking part in Mindfulness-Based Cognitive Therapy.

PMID- 20040730
TI  - Depressive personality disorder: a comparison of three self-report measures.
AB  - Depressive personality disorder (DPD) was included in the appendix of the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
      for further study. Questions abound regarding this disorder in terms of its
      distinctiveness from extant diagnostic constructs and clinical significance.This
      study examines the interrelations between three assessments of DPD and their
      relations to pathological personality traits and disorders in a sample of
      undergraduates (N = 182). The DPD indices evinced adequate convergence with each
      other (mean r = .60) and similar pathological personality profiles. The authors
      also tested the incremental validity of the DPD scores in relation to
      psychological functioning, after controlling for depressive symptoms and the DSM
      IV personality disorders (PDs). The DPD scores manifested limited incremental
      validity, mainly in the form of predicting lower levels of positive affectivity.
      Our results suggest that this is not specific to DPD, however, as the official
      PDs also manifested limited incremental validity.

PMID- 20040731
TI  - Depression in adoptive parents: a model of understanding through grounded theory.
AB  - A limited number of studies have explored parental depression in the postadoption
      time periods and these studies frequently lack a social context of the adoptive
      parent experience. The objective of this study is to form a midrange theoretical
      interpretation of parental postadoption depression as shared by adoptive parents
      and experts through a grounded theory approach. Semistructured interviews of
      adoptive parents, who acknowledge being depressed after the child is placed in
      the home, and adoption experts are audiotaped, transcribed, and coded to reveal
      themes. In total, 30 interviews are conducted. Researchers are also participant
      observers during an adoptive parent support group meeting. Data reveal recurrent
      themes in relation to postadoption depression. These themes take into account the
      various contexts of adoption (international and domestic, public and private,
      etc.). Parents express unfulfilled and unrealistic expectations in the domains of
      self, child, family or friends, and society or others. A theoretical model is
      presented to facilitate the understanding of depression reported by adoptive
      parents.

PMID- 20040733
TI  - Grounded theory and feminist inquiry: revitalizing links to the past.
AB  - Grounded theory has served feminist research endeavors since the mid-1990s.
      Researchers from a variety of disciplines claim methodological compatibility and
      incorporate feminist principles into their grounded theory studies. This article
      seeks to demonstrate the epistemological affinity between feminist inquiry and
      grounded theory. Although this relationship is not necessarily unique, the
      authors contend that when combined, it loosens the androcentric moorings of the
      empirical processes underpinning grounded theory, enabling the researchers to
      design inquiry with greater potential to reveal issues particular to the lives
      and experiences of marginalized women. The article begins by retracing the roots
      of grounded theory and feminist inquiry to identify six key areas where the
      underpinnings of GT are enriched by a feminist perspective when working with
      women. In addition, the authors draw on the literature and their experience from
      a 2005 study of peer support and lone mothers' health to demonstrate the
      advantages of combining these theoretical perspectives. Finally, the authors
      recommend that nurse researchers draw on feminist principles to guide their use
      of grounded theory to better serve the interests of women by surfacing issues of
      gender and power that influence the health experience.

PMID- 20040732
TI  - Review of intervention studies promoting physical activity in Hispanic women.
AB  - The objectives of this review are to (a) provide a comprehensive review and
      evaluation of intervention studies designed to promote physical activity among
      Hispanic women and (b) provide recommendations for future research involving
      Hispanic women in physical activity intervention research. Computer and manual
      searches have been conducted of articles in the English-language literature from
      1980 to present. Twelve articles are evaluated that emphasize physical activity
      interventions in Hispanic women. A review of current intervention research
      provides a starting point for determining salient approaches for intervention and
      evaluation, issues related to program implementation, and the strengths and
      limits of existing approaches. During the past 30 years, very few interventions
      have been conducted that examine physical activity among Hispanic women; those
      that include Hispanic women across ages support the need for interventions that
      build on the strengths and address the limitations of this body of research.

PMID- 20040734
TI  - Suicidal ideation in adolescents: an explanatory model using LISREL.
AB  - Suicidal ideation has been reported to be a major factor in attempted and
      completed suicides. The purpose of this study is to test a structural model to
      explain adolescent suicidal ideation. Specifically tested is the relationship
      between the predictor variables of trait anger, anger suppression, entrapment,
      psychosomatic symptoms, depression, and resilience and the dependent variable of
      suicidal ideation. Data are collected from a convenience sample of 11,393
      students from 36 middle schools and 23 high schools in Korea. Trait anger,
      entrapment, psychosomatic symptoms, depression, and resilience have a direct
      effect on suicidal ideation whereas anger suppression shows a significant
      indirect effect on adolescent suicidal ideation. The predictor variables account
      for 39% of the variance in suicidal ideation. The study findings suggest that
      future programs for prevention or alleviation of adolescents' suicidal ideation
      need to use interventions that facilitate their resilience and reduce their
      anger, entrapment feeling, psychosomatic symptoms, and depression.

PMID- 20040735
TI  - Quality of life and sugar and fiber intake in women with irritable bowel
      syndrome.
AB  - The purpose of this study is to examine quality of life (QOL) and dietary
      constituents in three subgroups of women with irritable bowel syndrome (IBS)
      based on the severity of their bloating symptoms. A secondary analysis of data
      from two studies of women with IBS (n = 183), ages 18 to 48, is performed.
      Measures include the Modified Flanagan Quality of Life Scale and a 3-day food
      record ( n = 95) and a daily symptom diary completed over a month. There are no
      differences in QOL and few differences in dietary intake, although women with the
      most severe bloating report less dietary intake of fructose ( p = .035) as
      compared with the women with less severe bloating symptoms. The findings suggest
      that women with IBS who experience moderate to severe bloating symptoms may not
      reduce their dietary intake except fructose.

PMID- 20040736
TI  - Adaptations to achieve physical activity in rural communities.
AB  - This multiple, descriptive, explanatory case study design described and explained
      the perceptions of rural women regarding rural built environments conducive to
      physical activity. Sources of data included women's focus groups, city council
      focus groups, city administrator and clerk interviews, women's verification
      individual interviews, individuals referred to the researcher as individuals with
      perceived power, and analysis of documents. The study involved two rural
      communities with populations of 1,000 or less, and data were collected between
      March 2006 and April 2007. Content analysis of each data source and a combined
      data source analysis for each community was completed using NVivo7. Rural women
      adapted to conditions of built environments, seasonal concerns, wild animals,
      traffic control issues, other people, and personal needs. Adaptation emerged as a
      central theme in the women's focus groups as a way rural women engaged in
      physical activity.

PMID- 20040737
TI  - Curcumin produces an antihyperalgesic effect via antagonism of TRPV1.
AB  - Curcumin has diverse therapeutic effects, such as anti-inflammatory, anti
      oxidant, anti-cancer, and antimicrobial activities. The vanilloid moiety of
      curcumin is considered important for activation of the transient receptor
      potential vanilloid 1 (TRPV1), which plays an important role in nociception.
      However, very little is known about the effects of curcumin on nociception. In
      the present study, we investigated whether the anti-nociceptive effects of
      curcumin are mediated via TRPV1 by using nociceptive behavioral studies and in
      vitro whole-cell patch-clamp recordings in the trigeminal system. Subcutaneous
      injection of capsaicin in the vibrissa pad area of rats induced thermal
      hyperalgesia. Intraperitoneally administered curcumin blocked capsaicin-induced
      thermal hyperalgesia in a dose-dependent manner. Whereas curcumin reduced
      capsaicin-induced currents in a dose-dependent manner in both trigeminal ganglion
      neurons and TRPV1-expressing HEK 293 cells, curcumin did not affect heat-induced
      TRPV1 currents. Taken together, our results indicate that curcumin blocks
      capsaicin-induced TRPV1 activation and thereby inhibits TRPV1-mediated pain
      hypersensitivity.

PMID- 20040738
TI  - Effects of rehydration on dentin strengthened by heating or UV irradiation.
AB  - Type I collagen, the major organic component of human dentin, plays an important
      role in regulating the mechanical strength of dentin. Collagen in dentin can be
      strengthened by heating. We hypothesized that UV irradiation could produce
      similar strengthening effects and might maintain the strength of dentin after
      rehydration. Beam-shaped dentin specimens from the crowns of human third molars
      were subjected to flexural testing. Flexural strengths were two and three times
      greater than those in the control group after 5 minutes' UV irradiation and
      heating to 140 degrees C, respectively. After 30 days of rehydration, the heated
      specimens reverted to their original strength, whereas the UV specimens were 69%
      stronger than the original. Raman spectra of dental collagen were unchanged after
      heating, whereas several peaks, including a C-C bond in a proline ring, were
      amplified by UV irradiation. It is concluded that dentin strengthened by UV
      irradiation retains strength after rehydration because of chemical changes in
      collagen.

PMID- 20040739
TI  - NOD1 and NOD2 mediate sensing of periodontal pathogens.
AB  - In bacterial infection, Nucleotide-binding Oligomerization Domain (NOD) 1 and
      NOD2 induce innate immune responses by recognizing fragments of the bacterial
      component peptidoglycan (PGN). To determine the roles of these receptors in
      detection of periodontal pathogens, we stimulated human embryonic kidney cells
      expressing NOD1 or NOD2 with heat-killed Porphyromonas gingivalis,
      Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum or their
      soluble PGNs (sPGNs). All bacteria and their sPGNs could stimulate activation of
      NF-kappaB. However, there were differences in NOD1- and NOD2-stimulatory
      activities among the species of bacteria. P. gingivalis showed weaker NOD1- and
      NOD2-stimulatory activities than did other bacteria. These differences in
      activities were confirmed by production of interleukin-8 from oral epithelial
      cells stimulated with sPGNs. These findings indicate that both NOD1 and NOD2
      might be involved in the recognition of periodontal pathogens, and that the weak
      NOD-stimulatory property of P. gingivalis might be helpful for survival in the
      periodontal pocket.

PMID- 20040740
TI  - Synergy of TLR2 and H1R on Cox-2 Activation in Pulpal Cells.
AB  - Although pulp fibroblasts are a major cell type in dental pulp, their roles in
      microbial recognition and pulpal inflammation are not well-understood.
      Considering the pivotal role of Toll-like receptors (TLRs) in the recognition of
      micro-organisms, we hypothesized that TLRs on pulp fibroblasts may induce
      inflammatory signals in dental pulp. In human pulp fibroblasts, TLR2, 3, 4, and 5
      were constitutively expressed. Stimulation of TLR2 and 3 induced the expression
      of pro-inflammatory genes such as CXCL10, CCL5, and/or Cox-2 in pulp fibroblasts.
      Interestingly, histamine synergistically activated TLR2-mediated Cox-2 expression
      and PGE(2) production. The synergistic effect of histamine is mediated by
      histamine receptor-1 (H1R). Studies on the intra-cellular signaling pathways
      revealed that p38 activation is required for the synergistic activation of Cox-2
      by TLR2 and histamine. Analysis of these data suggests that TLR2 on pulp
      fibroblasts, in concert with H1R, can induce an inflammatory response during
      microbial infection in dental pulp.

PMID- 20040741
TI  - Periodontal treatment completed before the 35th week of pregnancy appeared to
      have a beneficial effect on birthweight and time of delivery. Letter to the
      editor.

PMID- 20040742
TI  - Zeta-potential and particle size analysis of human amelogenins.
AB  - The developing enamel matrix is a highly dynamic system mainly composed of the
      full-length amelogenin and its proteolytic cleavage products. In this study,
      size, zeta-potential, and the isoelectric points of nanoparticles of the
      recombinant full-length human amelogenin (rH174) and two proteolytic products
      (rH163 and rH146) were analyzed by dynamic light-scattering and electrokinetic
      measurements. We tested the hypothesis that zeta-potential may be used as a
      control parameter in directing the self-assembly of amelogenins. Extensive
      aggregation of amelogenin molecules with the particle size reaching about one
      micron occurred at a mildly acidic to neutral pH, and coincided with the red
      shift of the internal fluorescence. Zeta-potential was between +/- 15 mV in the
      same pH range, indicating that amelogenin aggregation occurred when surface
      potentials were minimal. This suggests that electrostatic interactions may be
      another crucial factor, aside from hydrophobic interaction, in the aggregation
      and hierarchical assembly of spherical particles of amelogenins into
      supramolecular structures of a higher order.

PMID- 20040743
TI  - Exploring the research decision space: the expected value of information for
      sequential research designs.
AB  - PURPOSE: To investigate the expected value of partial perfect information (EVPPI)
      and the research decisions it can address. METHODS: Expected value of information
      (EVI) analysis assesses the expected gain in net benefit from further research.
      Where the expected value of perfect information (EVPI) exceeds the costs of
      additional research, EVPPI can be used to identify parameters that contribute
      most to the EVPI and parameters with no EVPPI that may be disregarded as targets
      for further research. Recently, it was noted that parameters with low EVPPI for a
      one-off RESEARCH DESIGN: may be associated with high EVPPI when considered as
      part of a sequential design. This article examines the characteristics and role
      of conditional and sequential EVPPI in EVI analysis. RESULTS: The calculation of
      EVPPI is demonstrated for single parameters, groups of parameters, and
      conditional and sequential EVPPI. Conditional EVPPI is the value of perfect
      information about one parameter, conditional on having obtained perfect
      information about another. Sequential EVPPI is the value of perfect information
      for a sequential research design to investigate first one parameter, then
      another. Conditional EVPPI differs from the individual EVPPI for a single
      parameter. Sequential EVPPI includes elements from the joint EVPPI for the
      parameters and the EVPPI for the first parameter in sequence. Sequential designs
      allow abandonment of research on the second parameter on the basis of additional
      information obtained on the first. CONCLUSIONS: The research decision space
      addressed by EVI analyses can be widened by incorporating sequential EVPPI to
      assess sequential research designs.

PMID- 20040744
TI  - Implementing regulation policy in Brazilian health care regulation centers.
AB  - The regulation of specialist medical appointments represents one of the
      problematic areas of the Brazilian Public Health System. In this regulation
      process, 2 issues stand out: 1) which patients should have the highest attendance
      priority, and 2) which service suppliers can best resolve the specific health
      problem of a patient? Based on the consideration of the existing Brazilian
      context in the field of medical assistance, this study proposes a model designed
      to aid regulation centers deal with the decisions related to the process of
      allocating specialist medical appointments. The model integrates multicriteria
      decision analysis and linear programming for the specialist medical appointment
      allocation, in which the allocation of patients is defined as a function of the
      relative significance of a set of criteria related to the notion of effectiveness
      of the specialist medical care and the capability of the accredited specialist
      health care units. The integrated model was implemented in a computer-based
      system and validated using cardiology and vein surgery data from the regulation
      center in Porto Alegre, Brazil. The validated computational system was applied to
      mammography services in another regulation center. The system successfully
      implemented a prioritization scheme, decreasing significantly the examination
      waiting time of severe cases.

PMID- 20040746
TI  - Novel morphological traits in the early developmental stages of Temnopleurus
      toreumaticus.
AB  - We have re-observed in detail the development of the sea urchin species
      Temnopleurus toreumaticus, which is considered to be a typical indirect
      developing species with a feeding larval stage. In this re-observation, we
      discovered two new morphological traits in the early embryonic stages of T.
      toreumaticus. The first trait is that, immediately after fertilization, the egg
      enters a stage in which wrinkles form on its surface as a result of actin
      polymerization. The second new trait is that the blastulae form wrinkles; in sea
      urchins, this has previously been known only in direct-developing species that
      have a nonfeeding larval stage and form wrinkles during the blastula stage,
      before hatching. These phenomena indicate that after fertilization, the egg of T.
      toreumaticus undergoes a surface transformation that is unprecedented in
      echinoderms, and that an indirect-developing sea urchin can form a wrinkled
      blastula.

PMID- 20040747
TI  - Analysis of the intermediary metabolism of a reductive chemoautotroph.
AB  - All extant life forms depend, directly or indirectly, on the autotrophic fixation
      of the dominant elements of the biosphere: carbon, hydrogen, nitrogen, oxygen,
      phosphorus, and sulfur. We have earlier presented the canonical network of
      reactions that constitute the anabolism of a reductive chemoautotroph. Separating
      this network into subgraphs reveals several empirical generalizations: (1)
      acetate (acetyl-CoA), pyruvate, phosphoenol pyruvate, oxaloacetate, and 2
      oxoglutarate serve as universal starting points for all pathways leading to the
      universal building blocks-20 amino acids and 4 ribonucleotide triphosphates; (2)
      all pathways are anabolic; (3) all reactions operate by complete utilization of
      outputs with no molecules left behind as waste, ensuring conservation of
      information; (4) the core metabolome of 120 compounds is acidic, consisting of
      compounds containing phosphoric or carboxylic acid or both; and (5) the core
      network is both brittle-vulnerable to a single break-and robust-having persisted
      for 4 billion years. Preliminary analysis of the chemical reactions and resultant
      structures reveals (a) a sparseness among possible molecular structures; (b)
      subdomains in the network; and (c) restriction of anabolism to a small set of
      rudimentary organic reactions with limited diversity in chemical mechanisms.
      These generalizations have implications for biogenesis and trophic ecology.

PMID- 20040748
TI  - Mitochondrial and nuclear DNA analysis of genetic heterogeneity among recruitment
      cohorts of the European flat oyster Ostrea edulis.
AB  - Marine species with high fecundity and high early mortality may also have high
      variance in reproductive success among individuals due to stochastic factors,
      making successful reproduction a "sweepstakes." In some cases, the impact is
      sufficient to reduce the effective number of breeders in wild populations. We
      tested two predictions of the sweepstakes reproductive success hypothesis in a
      French Atlantic population of the European flat oyster, Ostrea edulis, by
      evaluating (1) whether individuals belonging to temporally discrete recruitment
      cohorts within a single reproductive season displayed reduced genetic variation
      relative to the entire adult population, and (2) whether these temporal cohorts
      of recruits were genetically differentiated from each other. We assayed genetic
      variation at four nuclear microsatellites and a 12S mitochondrial fragment in
      four recruitment cohorts. Nuclear markers provided no evidence for
      differentiation between recruitment cohorts and adults or between temporal
      cohorts. However, mitochondrial data indicate that the first temporal cohort
      showed significant differentiation with the last (Fst = 0.052, P < 0.05) and with
      the adult sample (Fst = 0.058, P < 0.05). These differences are most likely due
      to the smaller effective size of the mitochondrial genome-and hence its increased
      sensitivity to drift compared to the nuclear genome. This slight mitochondrial
      signal indicates a certain limitation in the number of contributing female
      parents in this species. The "sweepstakes" phenomenon was therefore limited in
      our case. Hypothetically, this phenomenon may occur or not, with a high variance
      as a result of the interaction between the oyster reproductive biology and
      different environmental conditions.

PMID- 20040749
TI  - Sublethal predation and regeneration in two onuphid polychaetes: patterns and
      implications.
AB  - We examined sublethal predation in the polychaete Diopatra cuprea, an important
      ecosystem engineer of intertidal and shallow subtidal marine sediments in the
      western Atlantic. D. cuprea commonly loses its antennae and portions of its
      anterior to predator attacks; these lost body portions are subsequently
      regenerated. We asked (i) if the intensity of sublethal predation differs for D.
      cuprea populations in Virginia versus Florida, (ii) if sublethal predation varies
      temporally in each region, and (iii) if sublethal predation influences activity
      and tube-building rates. Within Florida, we also drew comparisons between D.
      cuprea and the closely related onuphid Americonuphis magna. Surprisingly, we
      found that sublethal predation is more intense in Virginia than in Florida,
      likely making substantial contributions to secondary productivity. Within
      Florida, A. magna experienced more antennal loss than D. cuprea and is incapable
      of anterior regeneration. D. cuprea activity and tube-building rates are strongly
      influenced by anterior loss, but more subtly influenced by antennal loss. Given
      the observed rates of sublethal predation and population densities in Virginia
      versus Florida, sublethal predation is an important factor influencing D. cuprea
      populations and their associated communities.

PMID- 20040750
TI  - Unusual development of the mitraria larva in the polychaete Owenia collaris.
AB  - Despite the wide variety of larval forms among polychaetes, most are clearly
      derived from the canonical spiralian trochophore. Within the genus Owenia (family
      Oweniidae), however, the mitraria larva lacks the characteristic ciliary bands of
      the trochophore, and those it has are monociliated, typically a deuterostome
      characteristic. Adult Owenia spp. also possess a monociliated epidermis and
      deuterostome-like nephridia. This study is the first detailed account of early
      embryology for any member of the Oweniidae. Light, confocal, and scanning
      electron microscopy were used to investigate organogenesis from fertilization
      through metamorphosis in Owenia collaris. Equal spiral cleavage yields an embryo
      with an unusually large blastocoel for a spiralian. The embryo undergoes
      gastrulation by invagination, and begins swimming 24 h after fertilization. Three
      important events deviate markedly from stereotypical polychaete embryogenesis.
      First, at the 8-cell stage the micromeres are larger than the macromeres, as in
      nemerteans. Second, the blastopore becomes the anus, as in some deuterostomes,
      while the stomodeum may form secondarily. Third, the cells that would form the
      prototroch in a canonical spiralian trochophore (1q(2) descendants) never undergo
      cleavage arrest, and the primary ciliated band of the mitraria never contains
      large, multiciliated cells. The mitraria larva thus represents a mixture of
      protostome and deuterostome developmental traits, suggesting that spiralian
      development is not so rigidly constrained as it might appear.

PMID- 20040751
TI  - Elevated temperature affects development, survivorship, and settlement of the
      elkhorn coral, Acropora palmata (Lamarck 1816).
AB  - Elevated seawater temperatures during the late summer have the potential to
      negatively affect the development and survivorship of the larvae of reef corals
      that are reproductive during that time of year. Acropora palmata, a major
      Caribbean hermatype, reproduces annually during August and September. A. palmata
      populations have severely declined over the past three decades, and recovery will
      require high recruitment rates. Such recruitment will be limited if larval supply
      is reduced by elevated temperatures. The effects of elevated temperatures on
      development, survival, and larval settlement of A. palmata were investigated by
      culturing newly fertilized eggs at temperatures ranging from 27.5 to 31.5 degrees
      C. Development was accelerated and the percentage of developmental abnormalities
      increased at higher temperatures. Embryo mortality peaked during gastrulation,
      indicating that this complex developmental process is particularly sensitive to
      elevated temperatures. Larvae cultured at 30 and 31.5 degrees C experienced as
      much as an 8-fold decrease in survivorship compared to those at 28 degrees C.
      Additionally, settlement was 62% at 28 degrees C compared to 37% at 31.5 degrees
      C. These results indicate that embryos and larvae of A. palmata will be
      negatively affected as sea surface temperatures continue to warm, likely reducing
      recruitment and the recovery potential of A. palmata on Caribbean reefs.

PMID- 20040752
TI  - Functional morphology and fluid interactions during early development of the
      scyphomedusa Aurelia aurita.
AB  - Scyphomedusae undergo a predictable ontogenetic transition from a conserved,
      universal larval form to a diverse array of adult morphologies. This transition
      entails a change in bell morphology from a highly discontinuous ephyral form,
      with deep clefts separating eight discrete lappets, to a continuous solid
      umbrella-like adult form. We used a combination of kinematic, modeling, and flow
      visualization techniques to examine the function of the medusan bell throughout
      the developmental changes of the scyphomedusa Aurelia aurita. We found that flow
      around swimming ephyrae and their lappets was relatively viscous (1 < Re < 10)
      and, as a result, ephyral lappets were surrounded by thick, overlapping boundary
      layers that occluded flow through the gaps between lappets. As medusae grew,
      their fluid environment became increasingly influenced by inertial forces (10 <
      Re < 10,000) and, simultaneously, clefts between the lappets were replaced by
      organic tissue. Hence, although the bell undergoes a structural transition from
      discontinuous (lappets with gaps) to continuous (solid bell) surfaces during
      development, all developmental stages maintain functionally continuous paddling
      surfaces. This developmental pattern enables ephyrae to efficiently allocate
      tissue to bell diameter increase via lappet growth, while minimizing tissue
      allocation to inter-lappet spaces that maintain paddle function due to boundary
      layer overlap.

PMID- 20040753
TI  - Cryptic species differentiated in Conus ebraeus, a widespread tropical marine
      gastropod.
AB  - Anomalous mitochondrial and nuclear gene sequences in individuals of the widely
      distributed tropical marine gastropod Conus ebraeus that were not distinguishable
      by shell shape and color pattern characters suggested the presence of a second,
      cryptic species. We tested this hypothesis by genetic, morphological, and
      ecological comparisons of additional individuals from the site in Okinawa where
      the two forms co-occurred. Radular tooth size and shape, prey type in nature, and
      microhabitats utilized differed markedly between the two forms. Adults with
      typical C. ebraeus DNA and radular teeth preyed primarily on errant polychaetes
      (Eunicidae); those with anomalous DNA and teeth ate mainly sedentary capitellids.
      Juveniles (shell length <13 mm) had more similar teeth and ate primarily syllids.
      Radular teeth of the anomalous form agreed with those of Conus judaeus,
      distinguished from C. ebraeus by Rudolph Bergh in 1895 solely on tooth characters
      of one specimen from the Philippines. Samples from other widely scattered Pacific
      localities revealed only typical C. ebraeus gene sequences. Both forms occurred
      in Seychelles (western Indian Ocean), where their radular teeth and diets were
      consistent with the data from Okinawa, but DNA of available material was
      degraded. Although C. judaeus was long dismissed as an aberrant specimen and
      junior synonym of C. ebraeus, our results support its validity as a distinct
      species. These results highlight the importance of molecular and radular tooth
      characters relative to those of the shell. Moreover, cryptic species could well
      be important components of species richness in Conus specifically and marine
      molluscan biodiversity more generally.

PMID- 20040754
TI  - Methods for karyotyping and for localization of developmentally relevant genes on
      the chromosomes of the purple sea urchin, Strongylocentrotus purpuratus.
AB  - The purple sea urchin, Strongylocentrotus purpuratus, is the only non-chordate
      deuterostome model with a fully sequenced genome. Chromosomal localization of
      individual genes and resulting gene maps are unavailable for this or for any sea
      urchin. As a result, the purple sea urchin genome has not been mapped onto
      specific chromosomes and remains inaccessible to genome-wide approaches
      addressing questions that require positional information for particular genes.
      Here we describe the first successful methods for karyotyping and localizing
      specific gene loci on chromosomes of Strongylocentrotus purpuratus and those of
      the phylogenetically related Strongylocentrotus droebachiensis. Both species have
      42 chromosomes in their diploid genomes (n = 21). There are 2 large, 8 medium,
      and 10 small pairs, plus one putative sex pair. In both species, bindin genes
      were localized to 2 pair of homologous chromosomes by fluorescent in situ
      hybridization. Fluorescently labeled bacterial artificial chromosome clones
      generated from S. purpuratus for the functionally related genes brachyury, foxa,
      and foxb were localized to different chromosomes. Our protocols provide
      previously unavailable tools for developing a gene map for the purple sea urchin
      genome.

PMID- 20040755
TI  - GYRKPPFNGSIFamide (Gly-SIFamide) modulates aggression in the freshwater prawn
      Macrobrachium rosenbergii.
AB  - The freshwater prawn Macrobrachium rosenbergii is a tropical crustacean with
      characteristics similar to those of lobsters and crayfish. Adult males develop
      through three morphological types-small (SC), yellow (YC), and blue claws (BC)
      with each representing a level in the dominance hierarchy of a group, BC males
      being the most dominant. We are interested in understanding the role played by
      neuropeptides in the mechanisms underlying aggressive behavior and the
      establishment of dominance hierarchies in this type of prawn. SIFamides are a
      family of arthropod peptides recently identified in the central nervous system of
      insects and crustaceans, where it has been linked to olfaction, sexual behavior,
      and gut endocrine functions. One of the six SIFamide isoforms, GYRKPPFNGSIFamide
      (Gly-SIFamide), is highly conserved among decapod crustaceans such as crabs and
      crayfish. We wanted to determine whether Gly-SIFamide plays a role in modulating
      aggression and dominant behavior in the prawn. To do this, we performed
      behavioral experiments in which interactions between BC/YC pairs were recorded
      and quantified before and after injecting Gly-SIFamide directly into the
      circulating hemolymph of the living animal. Behavioral data showed that
      aggression among interacting BC/YC prawns was enhanced by injection of Gly
      SIFamide, suggesting that this neuropeptide does have a modulatory role for this
      type of behavior in the prawn.

PMID- 20040757
TI  - CC chemokine receptor 7 and 9 double-deficient hematopoietic progenitors are
      severely impaired in seeding the adult thymus.
AB  - T-cell development depends on recruitment of bone marrow-derived precursor cells
      to the thymus via a multistep adhesion cascade involving the chemokine receptor
      CCR9. However, CCR9 deficiency does not result in complete abrogation of
      progenitor entry into the adult thymus. Therefore, we tested the hypothesis that
      additional chemokine/chemokine receptor systems might play a role in this
      process. To this end, we generated mice deficient in both CCR9 and CCR7.
      Deficiency in both chemokine receptors resulted in severely reduced numbers of
      early T-cell progenitors and in near-complete abrogation of thymus
      reconstitution. Progenitors in bone marrow and peripheral blood remained largely
      unaffected in CCR7(-/-)CCR9(-/-) mice, and direct intrathymic transfer of
      precursors from CCR7(-/-)CCR9(-/-) mice as well as single-mutant mice showed that
      intrathymic differentiation of these precursors remained functional. Thus, our
      data reveal a previously unrecognized role of CCR7 in progenitor seeding of the
      adult thymus, which is largely masked by compensatory effects of CCR9 signals. In
      turn, CCR7 signals can partially compensate for CCR9 signals, thus explaining the
      rather mild phenotype of CCR9(-/-) mice with respect to progenitor seeding.

PMID- 20040758
TI  - Allogeneic T regulatory cell-mediated transplantation tolerance in adoptive
      therapy depends on dominant peripheral suppression and central tolerance.
AB  - T regulatory cells (Tregs) represent agents to mediate tolerance to allografts so
      that the use of immunosuppressive drugs is avoided. In this regard, we previously
      demonstrated that the adoptive transfer of allogeneic Tregs into IL-2Rbeta(-/-)
      mice prevented autoimmunity and led to allograft tolerance. Here, we investigated
      the requirements and mechanisms that favor this long-lasting tolerance. The most
      potent tolerance required exact matching of all alloantigens between the
      adoptively transferred allogeneic Tregs and allogeneic skin grafts, but tolerance
      to such allografts that lacked expression of major histocompatibility complex
      class I or II molecules also occurred. Thus, Tregs are not required to directly
      recognize major histocompatibility complex class II alloantigens to suppress skin
      transplant rejection. Depletion of allogeneic Tregs substantially, but not
      completely, abrogated this form of tolerance. However, thymocytes from allogeneic
      Treg adoptively transferred IL-2Rbeta(-/-) mice did not reject the corresponding
      allogeneic skin graft in secondary Scid recipients. Consistent with a requirement
      for a deletional mechanism in this IL-2Rbeta(-/-) model, a small number of wild
      type T cells readily abrogated the immune tolerant state. Collectively, these
      findings indicate that full tolerance induction is largely dependent on
      substantial Treg-mediated suppression and thymic deletion of alloreactive T cells
      and may represent general conditions for Treg-mediated transplantation tolerance.

PMID- 20040759
TI  - Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO
      classification.
AB  - Acute erythroid leukemia (AEL) is a rare type of acute myeloid leukemia (AML) for
      which diagnostic criteria have been refined in the 2008 World Health Organization
      (WHO) classification of AML. The relationship of AEL to myelodysplastic syndromes
      (MDSs) and to AML with myelodysplasia-related changes (AML-MRC) is not clearly
      defined. We conducted a retrospective, multi-institutional study of patients with
      AEL and compared them with patients with MDS or AML-MRC with erythroid
      hyperplasia (> or = 50% erythroid cells). Among a total of 124 patients with AEL,
      32% had a history of MDS or chronic cytopenia, 32% had therapy-related disease,
      and 35% had de novo disease. Sixty-four percent of patients had unfavorable AML
      risk-group karyotypes. FLT3 and RAS mutations were infrequent, occurring in 6%
      and 2%, respectively. The median overall survival (OS) of all AEL patients was 8
      months, comparable with that of patients with MDS or AML-MRC with erythroid
      hyperplasia. The OS was related to cytogenetic risk group, but not blast count or
      morphologic dysplasia. Our findings suggest that AEL is in the continuum of MDS
      and AML with erythroid hyperplasia, where karyotype rather than an arbitrary
      blast cutoff represents the most important prognostic factor.

PMID- 20040760
TI  - Results and factors influencing outcome after fully haploidentical hematopoietic
      stem cell transplantation in children with very high-risk acute lymphoblastic
      leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and
      Pediatric Disease Working Parties of the European Blood and Marrow Transplant
      group.
AB  - T cell-depleted haploidentical hematopoietic stem cell transplantation
      (haploHSCT) is an option to treat children with very high-risk acute
      lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127
      children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or
      third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia
      free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor
      analysis was performed for patients who underwent transplantation in remission (n
      = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS
      were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased
      RI was observed for children given a graft with higher number of CD34(+) cells
      (adjusted P = .09 and P = .07, respectively). In a multivariate analysis,
      haploHSCT performed in larger centers (performing > or = 231 allotransplantations
      in the studied period) was associated with improved LFS rate and decreased RI
      (adjusted P = .01 and P = .04, respectively), adjusting for different patient-,
      disease-, and transplant-related factors such as number of previous
      autotransplantations, cytomegalovirus serology status, type of T-cell depletion,
      and use of total body irradiation and antithymocyte globulin. In conclusion,
      higher CD34(+) cell dose and better patient selection may improve outcomes of
      children with ALL who undergo a haploHSCT. Transplant centers initiating programs
      on haploHSCT for children may collaborate with more experienced centers.

PMID- 20040761
TI  - SMAD7 controls iron metabolism as a potent inhibitor of hepcidin expression.
AB  - Hepcidin is the master regulatory hormone of systemic iron metabolism. Hepcidin
      deficiency causes common iron overload syndromes whereas its overexpression is
      responsible for microcytic anemias. Hepcidin transcription is activated by the
      bone morphogenetic protein (BMP) and the inflammatory JAK-STAT pathways, whereas
      comparatively little is known about how hepcidin expression is inhibited. By
      using high-throughput siRNA screening we identified SMAD7 as a potent hepcidin
      suppressor. SMAD7 is an inhibitory SMAD protein that mediates a negative feedback
      loop to both transforming growth factor-beta and BMP signaling and that recently
      was shown to be coregulated with hepcidin via SMAD4 in response to altered iron
      availability in vivo. We show that SMAD7 is coregulated with hepcidin by BMPs in
      primary murine hepatocytes and that SMAD7 overexpression completely abolishes
      hepcidin activation by BMPs and transforming growth factor-beta. We identify a
      distinct SMAD regulatory motif (GTCAAGAC) within the hepcidin promoter involved
      in SMAD7-dependent hepcidin suppression, demonstrating that SMAD7 does not simply
      antagonize the previously reported hemojuvelin/BMP-responsive elements. This work
      identifies a potent inhibitory factor for hepcidin expression and uncovers a
      negative feedback pathway for hepcidin regulation, providing insight into a
      mechanism how hepcidin expression may be limited to avoid iron deficiency.

PMID- 20040762
TI  - Intrathymic transplantation of bone marrow-derived progenitors provides long-term
      thymopoiesis.
AB  - The sustained differentiation of T cells in the thymus cannot be maintained by
      resident intrathymic (IT) precursors and requires that progenitors be replenished
      from the bone marrow (BM). In patients with severe combined immunodeficiency
      (SCID) treated by hematopoietic stem cell transplantation, late T-cell
      differentiation defects are thought to be due to an insufficient entry of donor
      BM progenitors into the thymus. Indeed, we find that the intravenous injection of
      BM progenitors into nonconditioned zeta-chain-associated protein kinase 70 (ZAP
      70)-deficient mice with SCID supports short- but not long-term thymopoiesis.
      Remarkably, we now show that the IT administration of these progenitors produces
      a significant level of donor-derived thymopoiesis for more than 6 months after
      transplantation. In contrast to physiologic thymopoiesis, long-term donor
      thymopoiesis was not due to the continued recruitment of progenitors from the BM.
      Rather, IT transplantation resulted in the unique generation of a large
      population of early c-Kit(high) donor precursors within the thymus. These ZAP-70
      deficient mice that received an IT transplant had a significantly increased
      prothymocyte niche compared with their untreated counterparts; this phenotype was
      associated with the generation of a medulla. Thus, IT administration of BM
      progenitors results in the filling of an expanded precursor niche and may
      represent a strategy for enhancing T-cell differentiation in patients with SCID.

PMID- 20040763
TI  - Oxidative stress-specific interaction between FANCD2 and FOXO3a.
AB  - The molecular pathway by which Fanconi anemia (FA) proteins function in oxidative
      stress response has not been defined. Here we report the functional interaction
      of the FA protein Fanconi anemia complementation group D2 (FANCD2) and the
      forkhead transcription factor forkhead box O 3a (FOXO3a). FOXO3a colocalized with
      FANCD2 foci in response to oxidative stress. The FANCD2-FOXO3a complex was not
      detected in cells deficient for the FA core complex component FANCA but could be
      restored in corrected cells. Consistent with this, a nonmonoubiquitinated FANCD2
      mutant failed to bind FOXO3a. Although both mitomycin C and ionizing radiation
      induced FANCD2 monoubiquitination, neither could induce the association of FANCD2
      and FOXO3a. Overexpression of FOXO3a reduced abnormal accumulation of reactive
      oxygen species, enhanced cellular resistance to oxidative stress, and increased
      antioxidant gene expression in corrected but not mutant FA-D2 cells. The novel
      oxidative stress response pathway identified in this study, in which FANCD2 and
      FOXO3a converge, probably contributes to cellular antioxidant defense.

PMID- 20040764
TI  - The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like
      protein 2 and appears to be encoded by an R>Q154 amino acid substitution.
AB  - The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet
      been defined despite evidence that HNA-3a-specific antibodies are particularly
      prone to cause severe, often fatal, transfusion-related lung injury. We used
      genome-wide single nucleotide polymorphism scanning and sequencing of DNA from
      persons of different HNA-3a/b phenotypes to identify a single single nucleotide
      polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid
      substitution in the first extracellular loop of choline transporter-like protein
      2, a member of the choline transporter-like protein family of membrane
      glycoproteins, and correlates perfectly with HNA-3a/b phenotypes (R154 encodes
      HNA-3a; Q154 encodes HNA-3b). Mass spectrometric analysis of proteins
      immunoprecipitated from leukocytes by anti-HNA-3a provided direct evidence that
      anti-HNA-3a recognizes choline transporter-like protein 2. These findings will
      enable large-scale genotyping for HNA-3a/b to identify blood donors at risk to
      have HNA-3a-specific antibodies and should facilitate development of practical
      methods to detect such antibodies and prevent transfusion-related lung injury.

PMID- 20040765
TI  - Placenta growth factor in sickle cell disease: association with hemolysis and
      inflammation.
AB  - Placenta growth factor (PlGF) is released by immature erythrocytes and is
      elevated in sickle cell disease (SCD). Previous data generated in vitro suggest
      that PlGF may play a role in the pathophysiology of SCD-associated pulmonary
      hypertension (PHT) by inducing the release of the vasoconstrictor, endothelin-1.
      In this cross-sectional study of 74 patients with SCD, we confirm that PlGF is
      significantly elevated in SCD compared with healthy control subjects. We found
      significantly higher levels of PlGF in SCD patients with PHT but observed no
      association of PlGF with the frequency of acute pain episodes or history of acute
      chest syndrome. The observed correlation between PlGF and various measures of red
      cell destruction suggests that hemolysis, and the resultant erythropoietic
      response, results in the up-regulation of PlGF. Although relatively specific,
      PlGF, as well as N-terminal pro-brain natriuretic peptide and soluble vascular
      cell adhesion molecule, has low predictive accuracy for the presence of PHT.
      Prospective studies are required to conclusively define the contribution of PlGF
      to the pathogenesis of PHT and other hemolytic complications in SCD.

PMID- 20040766
TI  - Autosomal dominant and sporadic monocytopenia with susceptibility to
      mycobacteria, fungi, papillomaviruses, and myelodysplasia.
AB  - We identified 18 patients with the distinct clinical phenotype of susceptibility
      to disseminated nontuberculous mycobacterial infections, viral infections,
      especially with human papillomaviruses, and fungal infections, primarily
      histoplasmosis, and molds. This syndrome typically had its onset in adulthood
      (age range, 7-60 years; mean, 31.1 years; median, 32 years) and was characterized
      by profound circulating monocytopenia (mean, 13.3 cells/microL; median, 14.5
      cells/microL), B lymphocytopenia (mean, 9.4 cells/microL; median, 4
      cells/microL), and NK lymphocytopenia (mean, 16 cells/microL; median, 5.5
      cells/microL). T lymphocytes were variably affected. Despite these peripheral
      cytopenias, all patients had macrophages and plasma cells at sites of
      inflammation and normal immunoglobulin levels. Ten of these patients developed 1
      or more of the following malignancies: 9 myelodysplasia/leukemia, 1 vulvar
      carcinoma and metastatic melanoma, 1 cervical carcinoma, 1 Bowen disease of the
      vulva, and 1 multiple Epstein-Barr virus(+) leiomyosarcoma. Five patients
      developed pulmonary alveolar proteinosis without mutations in the granulocyte
      macrophage colony-stimulating factor receptor or anti-granulocyte-macrophage
      colony-stimulating factor autoantibodies. Among these 18 patients, 5 families had
      2 generations affected, suggesting autosomal dominant transmission as well as
      sporadic cases. This novel clinical syndrome links susceptibility to
      mycobacterial, viral, and fungal infections with malignancy and can be
      transmitted in an autosomal dominant pattern.

PMID- 20040768
TI  - Retear patterns after arthroscopic rotator cuff repair: single-row versus suture
      bridge technique.
AB  - BACKGROUND: A subset of patients is often seen with an unusual pattern of tendon
      failure after arthroscopic rotator cuff repair using a suture bridge technique.
      PURPOSE: To evaluate retear patterns in cases with structural failure after
      arthroscopic primary repairs of rotator cuff tears. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: Forty-six cases revealing retear on magnetic
      resonance imaging performed at least 6 months after arthroscopic repair for the
      treatment of full-thickness rotator cuff tear were evaluated. A single-row
      technique had been performed in 19 cases and a suture bridge in 27 cases.
      According to retear patterns on postoperative magnetic resonance imaging, cases
      were divided into type 1 (cuff tissue repaired at the insertion site of rotator
      cuff was not observed remaining on the greater tuberosity) and type 2 (remnant
      cuff tissue remained at the insertion site in spite of retear). RESULTS: In the
      single-row group, 14 cases (73.7%) had type 1 and 5 cases (26.3%) type 2 retear.
      In the suture bridge group, 7 cases (25.9%) had type 1 and 20 cases (74.1%) type
      2. There were statistically significant differences between groups (P = .049).
      Extent of fatty degeneration of the rotator cuff did not affect retear patterns
      in the single-row group (P = .160). In the suture bridge group, the percentage of
      type 1 retear increased with severity of fatty degeneration (P = .030). Extent of
      muscle atrophy did not affect retear patterns of the single-row group; in the
      suture bridge group, the percentage of type 1 retear increased with severity of
      muscle atrophy (P = .904 vs .029). CONCLUSION: The suture bridge technique tended
      to better preserve the cuff tissue repaired to the insertion site of the rotator
      cuff than a single-row technique did; the retear in cases with a suture bridge
      technique was mainly in the musculotendinous junction. Direct retear at the
      footprint of the rotator cuff increased with severity of fatty degeneration or
      muscle atrophy in cases with a suture bridge technique.

PMID- 20040767
TI  - Duffy antigen receptor for chemokines (Darc) polymorphism regulates circulating
      concentrations of monocyte chemoattractant protein-1 and other inflammatory
      mediators.
AB  - To identify the genetic basis of circulating concentrations of monocyte
      chemoattractant protein-1 (MCP-1), we conducted genome-wide association analyses
      for MCP-1 in 3 independent cohorts (n = 9598). The strongest association was for
      serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC, the
      gene for Duffy antigen receptor for chemokines, a known vascular reservoir of
      proinflammatory cytokines (minor allele frequency, 45.6%; P < 1.0 * 10(-323)).
      This association was supported by family-based genetic linkage at a locus
      encompassing the DARC gene (genome-wide P = 8.0 * 10(-13)). Asp42Gly accounted
      for approximately 20% of the variability in serum MCP-1 concentrations and also
      was associated with serum concentrations of interleukin-8 and RANTES. While
      exploring a lack of association between this polymorphism and EDTA plasma MCP-1
      concentrations (P = .82), we determined that both clotting and exogenous heparan
      sulfate (unfractionated heparin) released substantial amounts of MCP-1 from Darc.
      Quantitative immunoflow cytometry failed to identify meaningful Asp42Gly
      associated differences in Darc expression, suggesting that a functional change is
      responsible for the differential cytokine binding. We conclude that Asp42Gly is a
      major regulator of erythrocyte Darc-mediated cytokine binding and thereby the
      circulating concentrations of several proinflammatory cytokines. We have also
      identified for the first time 2 mechanisms for the release of reservoir
      chemokines with possible clinical implications.

PMID- 20040769
TI  - Skill level-specific differences in snowboarding-related injuries.
AB  - BACKGROUND: Snowboarding-related injuries have been associated with specific
      snowboarding skill levels, but differences in specific skill level have not been
      identified. HYPOTHESIS: Injury patterns are different among skill levels. STUDY
      DESIGN: Descriptive epidemiology study. METHODS: The subjects were 19 539
      snowboarders from the Oku-Mino region in Gifu Prefecture, Japan, who were
      admitted to our hospital during the 12 snowboarding seasons from 1996 to 2008.
      They were asked to complete a questionnaire regarding age, gender, self-estimated
      skill level, injury location, injury type, mechanism of injury, and protective
      gear. Physicians documented diagnostic variables and injury severity score; these
      variables were compared among the self-estimated skill levels. RESULTS: Of the
      total 19 539 injured snowboarders, 1204 (6.2%) were novices, 6409 (32.8%) were
      beginners, 9260 (47.4%) were intermediates, 1918 (9.8%) were experts, and the
      skill level was not known in 748 (3.8%). Proportions of the trunk and multiple
      injuries increased with increases in skill level; however, the number of
      head/face injuries decreased with increase in skill level. Upper extremity
      injuries also decreased with increase in skill level, except in novices.
      Dislocations and multiple injuries increased with increase in skill level, while
      lacerations/contusions, fractures, and bruises decreased. The mean overall injury
      severity score was 3.28 + or - 0.02, and the value increased significantly with
      increase in skill level. The proportion of collision and isolated fall injuries
      significantly decreased with increase in skill level, but that of jump injuries
      significantly increased. The percentage of protective gear use increased with the
      increase in skill level. CONCLUSION: Prevalence of injury type, injury location,
      mechanism of injury, and percentage of protective gear use varied according to
      skill level, and the severity of the injury increased with increase in skill
      level. On the basis of our observations, we believe that snowboarding injury
      prevention strategies should be formulated according to skill level.

PMID- 20040770
TI  - Sonoelastographic strain index for differentiation of benign and malignant
      nonpalpable breast masses.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic potential of
      the sonoelastographic strain index for differentiation of nonpalpable breast
      masses. METHODS: Ninety-nine nonpalpable breast masses (79 benign and 20
      malignant) in 94 women (mean age, 45 years; range, 21-68 years) who had been
      scheduled for a sonographically guided core biopsy were examined with B-mode
      sonography and sonoelastography. Radiologists who had performed the biopsies
      analyzed the B-mode sonograms and provided American College of Radiology Breast
      Imaging Reporting and Data System categories. The strain index (fat to lesion
      strain ratio) was calculated by dividing the strain value of the subcutaneous fat
      by that of the mass. The histologic result from the sonographically guided core
      biopsy was used as a reference standard. The diagnostic performance of the strain
      index and that of B-mode sonography were compared by receiver operating
      characteristic (ROC) curve analysis. RESULTS: The mean strain index values +/- SD
      were 6.57 +/- 6.62 (range, 1.29-28.69) in malignant masses and 2.63 +/- 4.57
      (range, 0.54-38.76) in benign masses (P = .019). The area under the ROC curve
      values were 0.835 (95% confidence interval [CI], 0.747-0.902) for B-mode
      sonography and 0.879 (95% CI, 0.798-0.936) for the strain index (P = .490). The
      sensitivity, specificity, positive predictive value, and negative predictive
      value were 95% (19 of 20), 75% (59 of 79), 48% (19 of 39), and 98% (59 of 60),
      respectively, when a best cutoff point of 2.24 was used. CONCLUSIONS: The strain
      index based on the fat to lesion strain ratio has diagnostic performance
      comparable with that of B-mode sonography for differentiation of benign and
      malignant breast masses.

PMID- 20040771
TI  - Role of Doppler ultrasonography in the triage of acute scrotum in the emergency
      department.
AB  - OBJECTIVE: The purpose of this study was to examine the triage role of scrotal
      Doppler ultrasonography (DUS) as the primary preoperative diagnostic tool in
      patients presenting to the emergency department (ED) with acute scrotum. METHODS:
      Patients who presented to the ED with acute scrotum and underwent scrotal DUS in
      the ultrasound unit over a 3-year period (2004-2007) were included in the study.
      Patient characteristics, DUS findings, and clinical management were
      retrospectively collected and reviewed. Doppler ultrasonographic diagnoses were
      compared with histopathologic findings for patients who underwent exploration and
      with final diagnoses at the time of discharge for patients undergoing medical
      treatment. RESULTS: A total of 620 consecutive patients with 669 DUS examinations
      were included. The most common scrotal DUS diagnoses were epididymitis,
      hydrocele, varicocele, and orchitis. Scrotal trauma was present in 77 cases.
      Hospitalization followed the initial ED evaluation for 155 patients; 68 underwent
      surgery. Testicular torsion was ultrasonographically suspected in 20 patients and
      confirmed in 18. Scrotal malignancy was incidentally diagnosed in 13 patients and
      testicular hematoma in 8. Doppler ultrasonography for the diagnosis of testicular
      torsion had 94% sensitivity, 96% specificity, 95.5% accuracy, an 89.4% positive
      predictive value (PPV), and a 98% negative predictive value (NPV). Doppler
      ultrasonography for the diagnosis of testicular malignancy had 92% sensitivity,
      95% specificity, 94% accuracy, a 78.5% PPV, and a 98% NPV. CONCLUSIONS: Scrotal
      DUS is a highly sensitive preoperative diagnostic tool, thereby validating its
      routine use in the initial triage of patients with acute scrotum presenting to
      the ED.

PMID- 20040772
TI  - Effect of observer experience in the differentiation between benign and malignant
      liver tumors after ultrasound contrast agent injection.
AB  - OBJECTIVE: The purpose of this study was to assess the impact of the observer
      level of experience on the diagnostic performance of contrast-enhanced ultrasound
      imaging (CEUS) for differentiation between benign and malignant liver tumors.
      METHODS: From a computerized search, we retrospectively identified 286 biopsy
      proven liver tumors (105 hepatocellular carcinomas, 48 metastases, 7 intra
      hepatic cholangiocarcinomas, 33 liver hemangiomas, and 93 nonhemangiomatous
      benign lesions) in 235 patients (140 male and 95 female; mean age +/- SD, 56 +/-
      11 years) who underwent CEUS after sulfur hexafluoride-filled microbubble
      injection. The digital cine clips recorded during the arterial (10-35 seconds
      from injection), portal (50-120 seconds), and late (130-300 seconds) phases were
      analyzed by 6 independent observers without experience (group 1, observers 1-3)
      or with 2 to 10 years of experience in CEUS (group 2, observers 4-6). Specific
      training in the diagnostic and interpretative criteria was provided to the
      inexperienced observers. Each observer used a 5-point scale to grade diagnostic
      confidence: 1, definitely benign; 2, probably benign; 3, indeterminate; 4,
      probably malignant; or 5, definitely malignant on the basis of the enhancement
      pattern during the arterial phase and enhancement degree during the portal and
      late phases compared with the liver (hypoenhancement indicating malignant and
      isoenhancement to hyperenhancement indicating benign). RESULTS: The analysis of
      observer diagnostic confidence revealed higher intragroup (kappa = 0.63-0.83)
      than intergroup (kappa = 0.47-0.63) observer agreement. The experienced observers
      showed higher diagnostic performance in malignancy diagnosis than did
      inexperienced observers (overall accuracy: group 1, 63.3%-72.8%; group 2, 75.9%
      93.1%; P < .05, chi(2) test). CONCLUSIONS: The diagnostic performance of CEUS in
      liver tumor characterization was dependant on the observer's level of experience.

PMID- 20040773
TI  - Correlation between substantia nigra features detected by sonography and
      Parkinson disease symptoms.
AB  - OBJECTIVE: The aim of this study was to assess the correlation between substantia
      nigra (SN) echogenic features and area and the clinical symptoms in patients with
      Parkinson disease (PD). METHODS: Clinical examinations and transcranial
      sonographic evaluations of the SN were performed in 115 consecutive patients with
      PD. The presence of tremors, rigidity, bradykinesia, gait disorders, speech
      disorders, and hypomimia was evaluated according to the motor portion of the
      Unified Parkinson Disease Rating Scale. The Mann-Whitney U test, the Kruskal
      Wallis test, analysis of variance, and multivariate analysis were applied when
      assessing statistical significance. RESULTS: An enlarged and hyperechoic SN
      existed in 84.0% of patients with bilateral rigidity but in only 70.6% of
      patients with unilateral rigidity (P < .05). Similarly, 85.0% of patients with
      bilateral bradykinesia in comparison with 65.7% of patients with unilateral
      bradykinesia had an enlarged and hyperechoic SN (P < .05). A significant
      correlation was shown between the SN echogenicity and area (r = 0.705; P < .01).
      Conclusions. An enlarged and hyperechoic SN seems to be a marker of structural
      involvement of the SN in patients with PD. This structural involvement is
      expressed more in patients with bilateral rigidity and bradykinesia.

PMID- 20040774
TI  - Mitochondrial damage in nasopharyngeal carcinoma cells induced by ultrasound
      radiation in the presence of hypocrellin B.
AB  - OBJECTIVE: The mitochondrion is an important target of ultrasound-induced cell
      death. This study aimed to investigate the mitochondrial damage in nasopharyngeal
      carcinoma (NPC) cells induced by ultrasound radiation in the presence of
      hypocrellin B (HB). METHODS: The NPC cell line CNE2 was used to investigate the
      effect of HB on ultrasonic action with an HB concentration of 2.5 mumol/L and
      ultrasound exposure for 15 seconds at an intensity of 0.65 W/cm(2). Cytotoxicity
      was investigated 24 hours after ultrasound exposure. Mitochondrial structure
      changes were observed by transmission electron microscopy. The mitochondrial
      membrane potential was evaluated by confocal laser-scanning microscopy with
      rhodamine 123 staining. RESULTS: The mean death rates of the CNE2 cells +/- SD
      were 25.14% +/- 1.50% after ultrasound radiation alone and 76.72% +/- 1.13% after
      ultrasound radiation in the presence of HB. Transmission electron microscopy
      showed that slightly enlarging mitochondria were found in the ultrasound-treated
      cells. After treatment with ultrasound and HB together, some cells had seriously
      damaged mitochondria, namely, obvious swollen mitochondria and mitochondria in
      which cristae had almost completely disappeared. The mitochondrial membrane
      potential was more significantly collapsed when the CNE2 cells were exposed to HB
      for 5 hours and then ultrasound at 0.65 mW/cm(2) than with ultrasound radiation
      alone (P < .05). CONCLUSIONS: Hypocrellin B significantly enhanced the
      cytotoxicity of ultrasound radiation in the CNE2 cells. The damage to the
      mitochondrial structure and function might be an important cause of death in the
      CNE2 cells induced by treatment with ultrasound radiation and HB together.

PMID- 20040775
TI  - Role of sonography for implantation and sequential evaluation of a VX2 rabbit
      liver tumor model.
AB  - OBJECTIVE: We investigated the role of sonography in the implantation process of
      a VX2 rabbit liver tumor model and sequential evaluation. METHODS: Fifty rabbits
      were divided into 2 groups. Animals in group I underwent surgical implantation,
      whereas those in group II received percutaneous sonographically guided
      implantation. At 7, 14, 21, and 28 days after implantation, respectively, 5
      rabbits in each group were examined with conventional, color Doppler (CD),
      contrast-enhanced (CE) pulse inversion harmonic (PIH), and CE CD sonography.
      Pathologic examination was performed with hematoxylin-eosin, nicotinamide adenine
      dinucleotide phosphate-diaphorase, and succinic dehydrogenase stains. RESULTS:
      Twenty-one rabbits with tumors survived in group I, and 22 with tumors survived
      in group II. The mean duration of implantation +/- SD in group II was 16.9 +/-
      3.4 minutes, whereas that in group I was 21.5 +/- 4.1 minutes (P < .05). The
      tumor volume measured by conventional sonography increased from 0.28 +/- 0.14
      cm(3) at 7 days to 16.49 +/- 5.50 cm(3) at 28 days in group I and from 0.31 +/-
      0.19 to 19.79 +/- 4.70 cm(3) in group II, whereas no significant difference
      existed between the groups. On CD, CE PIH, and CE CD sonography, most tumors were
      hypervascular before 14 days and after 14 days had peripheral vessels and central
      hypovascular areas, which were shown as necrotic areas by pathologic examination.
      CONCLUSIONS: Sonographically guided implantation achieved a good success rate
      with convenient inoculation performance. Conventional gray scale, CD, CE PIH, and
      CE CD sonography were useful in sequential evaluation of tumor growth and
      characteristic vascularity.

PMID- 20040776
TI  - Antitumor effect of docetaxel-loaded lipid microbubbles combined with ultrasound
      targeted microbubble activation on VX2 rabbit liver tumors.
AB  - OBJECTIVE: The purpose of the study was to explore the antitumor effect of
      docetaxel-loaded lipid microbubbles combined with ultrasound-targeted microbubble
      activation (UTMA) on VX2 rabbit liver tumors. METHODS: Docetaxel-loaded lipid
      microbubbles were made by a mechanical vibration technique. VX2 liver tumor
      models were established in 90 rabbits, which were randomly divided into 6 groups,
      including control, docetaxal-loaded lipid microbubbles alone, docetaxal alone,
      docetaxal combined with ultrasound, pure lipid microbubbles combined with
      ultrasound, and docetaxel-loaded lipid microbubbles combined with ultrasound
      (DOC+MB/US). The tumor volume and inhibition rate (IR) of tumor growth were
      calculated and compared. Apoptosis was detected by terminal deoxyuridine nick end
      labeling. Proliferating cell nuclear antigen and matrix metalloproteinase 2
      (MMP2) protein expression was detected by immunohistochemistry. Caspase 3 and
      MMP2 messenger RNA (mRNA) expression was detected by in situ hybridization
      histochemistry. The tumor metastasis rate and survival time of the animals were
      compared. RESULTS: The IR and apoptotic index of the DOC+MB/US group were the
      highest among all groups, and the proliferating labeling index was the lowest.
      Matrix metalloproteinase 2 protein and mRNA expression in the DOC+MB/US group was
      the lowest among all groups, and caspase 3 mRNA expression in the DOC+MB/US group
      was the highest. The extensive metastasis rate in the DOC+MB/US group was the
      lowest, and the survival time of the animals in the DOC+MB/US group was the
      longest. CONCLUSIONS: Docetaxel-loaded lipid microbubbles combined with UTMA
      could inhibit the growth of VX2 rabbit liver tumors by deferring proliferation
      and promoting apoptosis, which may provide a novel targeted strategy for
      chemotherapy of liver carcinoma.

PMID- 20040777
TI  - Transperineal sonocystography: new standard for assessing anastomotic leaks after
      radical prostatectomy.
AB  - OBJECTIVE: Fluorocystography (FC) is the reference standard for assessing the
      integrity of the vesicourethral anastomosis after radical prostatectomy (RP). We
      describe a new technique, transperineal sonocystography (TPSC), as a cost
      effective alternative and more informative than FC. METHODS: Between May 1, 2007,
      and October 1, 2008, 175 consecutive men underwent open or robotically assisted
      RP. Before Foley catheter removal, all men underwent both TPSC and FC, which were
      performed and interpreted by a single radiologist. Transperineal sonocystography
      was performed first with real-time imaging after gravity filling of the bladder
      with 150 mL of normal saline. Extravasation of saline was calculated by computer
      software after outlining the observed pooling of extravasated saline in the
      transverse and longitudinal views. Fluorocystography was performed after TPSC
      using our standard protocol, with qualitative classification of anastomotic leaks
      as none, slight, moderate, or severe. RESULTS: The mean extravasation volume +/-
      SEM was 16.3 +/- 2.9 mL. Of the 175 patients, 142 (81.2%) showed no anastomotic
      leaks on TPSC. Of the remaining 33 patients (18.8%), TPSC identified 20 (11.4%),
      13 (7.4%), and 0 patients with slight, moderate, and severe leaks, respectively.
      Excellent concordance was shown between TPSC and FC. CONCLUSIONS: Transperineal
      sonocystography was equivalent to FC in detecting anastomotic leaks after RP. It
      provides a safe, inexpensive, and effective alternative to traditional FC for
      evaluating the integrity of the vesicourethral anastomosis after RP.

PMID- 20040778
TI  - Use of sonography for airway assessment: an observational study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of
      sonography in identifying the anatomic structures of the upper airway and to
      describe their appearance on sonography. METHODS: We enrolled 24 healthy
      volunteers, placed them supine with their head extended and neck flexed (the
      "sniffing" position), and performed a systematic sonographic examination of their
      upper airway from the floor of the mouth to the suprasternal notch. RESULTS: We
      were able to visualize all relevant anatomic structures in all of the
      participants using either a linear or curved transducer oriented in 1 of 3
      planes: sagittal, parasagittal, and transverse. Bony structures (eg, the mandible
      and hyoid) were brightly hyperechoic with an underlying hypoechoic acoustic
      shadow. Cartilaginous structures (eg, the epiglottis, thyroid cartilage, cricoid
      cartilage, and tracheal rings) were hypoechoic, and their intraluminal surface
      was outlined by a bright air-mucosa interface. The vocal cords were readily
      visualized through the thyroid cartilage. However, the posterior pharynx,
      posterior commissure, and posterior wall of the trachea could not be visualized
      because of artifacts created by an intraluminal air column. CONCLUSIONS:
      Sonography of the upper airway is capable of providing detailed anatomic
      information and has numerous potential clinical applications.

PMID- 20040779
TI  - Sonographic anatomy of the gastrohepatic ligament.
AB  - OBJECTIVE: The purpose of this presentation is to illustrate anatomic and
      pathologic features of the gastrohepatic ligament (GHL) and to show its
      usefulness for precise localization of abnormalities, particularly in relation to
      the lesser peritoneal cavity and diseases occurring within the confines of the
      ligament itself. METHODS: Cases were selected that illustrate the objectives
      above. RESULTS: Illustrations show various anatomic and pathologic features meant
      to enhance interpretation of left upper quadrant sonograms. CONCLUSIONS:
      Illustrations seen in the sonographic literature vaguely interpret the
      relationships of the GHL. Misunderstanding has led not only to improper
      nomenclature but also to the use of inappropriate indicators of lesser omental
      diseases. With a clear understanding of the anatomy of the GHL and its use as a
      pivotal marker for structures around and within it, one can avoid these pitfalls
      and better evaluate adult and pediatric lesser omental anatomy.

PMID- 20040780
TI  - Three-dimensional ultrasound imaging of mammary ducts in lactating women: a
      feasibility study.
AB  - OBJECTIVE: The main function of the breast is to produce milk for offspring. As
      such, the ductal system, which carries milk from the milk-secreting glands
      (alveoli) to the nipple, is central to the natural function of the breast. The
      ductal system is also the region in which many malignancies originate and spread.
      In this study, we aimed to assess the feasibility of manual mapping of ductal
      systems from 3-dimensional (3D) ultrasound data and to evaluate the structures
      found with respect to conventional understanding of breast anatomy and
      physiology. METHODS: Three-dimensional ultrasound data of the breast were
      acquired using a mechanical system, which captures data in a conical shape
      covering most of the breast without excessive compression. Manual mapping of the
      ductal system was performed using custom software for data from 4 lactating
      volunteers. RESULTS: Observational results are presented for ultrasound data from
      the 4 lactating volunteers. For all volunteers, only a small number of ductal
      structures were engorged with milk, suggesting that the lactiferous activity of
      the breast may be localized. These enlarged ducts were predominantly found in the
      inferior lateral quadrant of each breast. The observation was also made that the
      enlarged, milk-storing parts of the duct were spread throughout the ductal system
      and not directly below the nipple as conventional anatomy suggests. CONCLUSIONS:
      Ultrasound visualization of the 3D structure of milk-laden ducts in an
      uncompressed breast has been shown. Using manual tracing, it was possible to
      track milk-laden ducts of diameters less than 1 mm.

PMID- 20040781
TI  - Sonographic findings of inguinal endometriosis.
AB  - OBJECTIVE: The purpose of this series was to describe the sonographic findings of
      inguinal endometriosis. METHODS: This was a retrospective analysis of 3 cases of
      inguinal endometriosis. The following gray scale and color Doppler sonographic
      features were analyzed: size, shape, echogenicity, and blood flow within inguinal
      endometriosis. RESULTS: The size of inguinal endometriosis ranged from 3.1 to 4.2
      cm (mean, 3.7 cm). All 3 cases were cystic lesions. Two of 3 cases were lesions
      with internal septa. On color Doppler sonography, 1 of the 3 cases showed a few
      flow signals within the lesion, whereas in 2 of the 3 lesions, no blood flow
      could be identified within the lesions. CONCLUSIONS: Although the sonographic
      features of inguinal endometriosis may be variable, endometriosis should be
      included in the differential diagnosis when unilocular and multilocular cystic
      masses are seen on sonography.

PMID- 20040782
TI  - The tortoiseshell pattern in one or both sides of the submandibular glands in
      mucosa-associated lymphoid tissue lymphoma is related to chromosomal aberrations
      and the disease extent.
AB  - OBJECTIVE: Lesions of mucosa-associated lymphoid tissue (MALT) lymphoma in the
      submandibular glands are localized or a part of systemic involvement in
      association with chromosomal aberrations. This series was undertaken to
      investigate the sonographic features of MALT lymphoma in the submandibular glands
      and their relationships with chromosomal aberrations and the disease extent.
      METHODS: A total of 5 patients with MALT lymphoma without Sjogren syndrome in the
      submandibular glands were enrolled in this series. Patients underwent sonography
      of the submandibular glands with a high-resolution transducer before surgical
      biopsy of the main lesion. Sonographic characteristics of the lesions were
      described for their location, presence of a posterior echo, texture, and presence
      of an internal echo. RESULTS: Sonography in all cases showed hypoechoic and solid
      masses with increased posterior echo enhancement. There was an arrangement of
      hypoechoic small compartments demarcated by hyperechoic contour lines, which had
      a tortoiseshell pattern. This pattern was classified into 2 types according to
      its location: a lesion in the right or left side and lesions in both sides of the
      submandibular glands, found in 3 and 2 patients, respectively. The latter 2 cases
      had chromosomal aberrations of t(11;18)(q23;q23) and t(12;18)(q22;q21),
      respectively, and were revealed as secondary organ involvement. CONCLUSIONS: The
      sonographic appearance of MALT lymphoma in the submandibular glands was
      characterized by the tortoiseshell pattern in both primary and secondary lesions.
      Detection of this pattern in both sides of the submandibular glands can be an
      indicator of chromosomal aberrations and systematic involvement of the disease.

PMID- 20040784
TI  - True diverticulum of the gallbladder.

PMID- 20040783
TI  - Appearance of absorbable gelatin compressed sponge on early post-thyroidectomy
      neck sonography: a mimic of locally recurrent or residual thyroid carcinoma.
AB  - OBJECTIVE: Absorbable gelatin compressed sponge (Gelfoam; Pfizer Inc, New York,
      NY), a biodegradable agent prepared from purified porcine skin gelatin, is
      frequently used for intraoperative hemostasis. Its appearance on sonography may
      mimic tumor or residual thyroid when placed in the resection bed after
      thyroidectomy. The purpose of this study was to describe the appearance of
      Gelfoam on early post-thyroidectomy sonography so that an erroneous diagnosis of
      locally recurrent or residual tumor can be avoided. METHODS: We reviewed the
      early postoperative sonographic examinations of 6 patients after thyroidectomy in
      which Gelfoam was used for hemostasis. Screening cervical sonography was
      performed to identify possible lateral compartment adenopathy before completion
      of thyroidectomy or ablation. Sonographic examinations were performed up to 50
      days after resection. Surgical reports confirmed the use of Gelfoam in each
      patient. RESULTS: In all cases, uniform elongated echogenicity was shown within
      the lobectomy bed. In 1 patient, sonographically guided fine-needle aspiration of
      lobectomy bed echogenicity yielded scant red blood cells, multinucleated giant
      cells, and macrophages. Follow-up sonography performed in 1 patient 14 months
      after thyroidectomy confirmed complete Gelfoam absorption. CONCLUSIONS: Gelfoam
      may mimic residual or recurrent thyroid carcinoma on early surveillance
      sonography performed after thyroidectomy. Recognition of its characteristic
      appearance should prompt a search for an appropriate surgical history and, when
      placed in the appropriate clinical context, should prevent an errant diagnosis of
      tumor.

PMID- 20040785
TI  - Vascular steal of the portal vein after orthotopic liver transplant:
      intraoperative sonographic diagnosis.
AB  - Spontaneous splenorenal shunts (SSRSs) are portosystemic connections between the
      splenic vein and the left renal vein (LRV) that develop commonly in patients with
      portal hypertension. (1) They reportedly occur in 18% to 19% of patients
      evaluated for a liver transplant. (2),(3) As the liver become more cirrhotic, a
      major steal phenomenon may occur, whereby blood is shunted from the high
      resistance venous bed of the liver to the lower systemic pressure of the LRV. (4)
      Not infrequently, an SSRS will go undetected during orthotopic liver
      transplantation because dissection is limited to the right upper quadrant. The
      importance of these shunts may be underappreciated preoperatively by the
      radiologist. Usually, if small, these shunts will involute without incident when
      the lower-resistance allograft is implanted. (5),(6) Larger varices, those
      greater than 10 mm at the level of transition into the LRV, are more likely to
      steal blood from the liver, causing allograft failure and possibly death.
      (4),(7),(8) It is therefore important to document on preoperative imaging the
      size and location of portosystemic varices in any patient being evaluated for
      liver transplantation. We present a case in which intraoperative sonography
      showed a large SSRS that impaired hepatic portal inflow after transplantation,
      ultimately resulting in the patient's death.

PMID- 20040786
TI  - Sonography in the identification of calciphylaxis of the breast.

PMID- 20040787
TI  - Serous adenofibroma of the testicle: case report and review of the literature.

PMID- 20040788
TI  - Bilateral intratesticular and extratesticular varicoceles secondary to extensive
      inferior vena cava thrombosis.

PMID- 20040789
TI  - Simultaneous obstruction of both limbs of a bifid ureter by calculi: sonographic
      evaluation.

PMID- 20040790
TI  - Pericardial and intracardiac metastasis of breast cancer.

PMID- 20040791
TI  - AIUM practice guideline for the performance of neurosonography in neonates and
      infants.

PMID- 20040792
TI  - AIUM practice guideline for the performance of obstetric ultrasound examinations.

PMID- 20040794
TI  - The cold hard facts of cryoglobulinaemia.

PMID- 20040793
TI  - AIUM practice guideline for the performance of pelvic ultrasound examinations.

PMID- 20040795
TI  - Apolipoprotein B, diabetes and medical consensus.

PMID- 20040796
TI  - Acute kidney injury: how do we define it?
AB  - Over recent years, there has been welcome increased interest in acute kidney
      injury (AKI) and its association with patient outcome. The term AKI has replaced
      the term acute renal failure (ARF) and encompasses all types of ARF. New
      definitions and staging systems for AKI have been proposed, which have stimulated
      a multitude of different studies to evaluate their clinical utility. These recent
      advances need to be communicated to the wider health care community so that we
      are using a shared nomenclature. In 2009 the National Confidential Enquiry into
      Patient Outcome and Death AKI study ('Adding Insult to Injury') announced its
      findings and recommendations. The report recommended that the detection of AKI
      and its management should be improved. These recommendations along with the
      adoption of the new staging systems will potentially have an impact on clinical
      biochemistry departments and exert an increased demand on resources. Running in
      parallel with these initiatives is the quest to discover novel biomarkers to
      detect AKI, the development and introduction of which will require laboratory
      support.

PMID- 20040797
TI  - Cryoglobulin evaluation: best practice?
AB  - Cryoglobulins are serum immunoglobulins that precipitate at temperatures below 37
      degrees C and re-dissolve on warming. Cryoglobulinaemia leads to variable
      symptoms including characteristic purpura, ischaemia of extremities, renal
      failure, peripheral neuropathy, abdominal pain secondary to intestinal ischaemia
      and arthralgias. Cryoglobulin testing is underutilized in clinical practice. It
      has been neglected in clinical laboratories and by clinicians due to several
      factors, such as the length of time it takes for serum cryoglobulin analysis to
      be performed in the laboratory, the perceived difficulty in getting optimal
      sampling conditions and a failure to appreciate that even apparently low levels
      of cryoglobulin can be associated with severe symptoms in some patients. The most
      important variable confounding standardization of cryoglobulin testing is
      improper sample handling. A recent report critically appraising the current
      practice of cryoglobulin evaluation in 137 laboratories in Europe by United
      Kingdom National External Quality Assurance Scheme (UKNEQAS) illustrated the wide
      variability in practice. Although many clinical laboratories perform cryoglobulin
      evaluation, there are widespread differences in the methodology used and the care
      with which this is carried out and this leads to considerable intralaboratory and
      interlaboratory variability. The most common sources of error are false-negative
      results due to loss of cryoprecipitate during transport and storage. Better
      standardization is needed to avoid missed diagnoses and improve the comparability
      of results. Laboratories should ensure that sample temperature is maintained at
      37 degrees C until the serum is separated. In this article, we briefly review the
      classification and clinical features of cryoglobulins and suggest best practice
      guidelines for laboratory detection and identification of cryoglobulins.

PMID- 20040798
TI  - Review of video-assisted thoracoscopy in children.
AB  - Open thoracotomy is the standard procedure for various thoracic diseases against
      which other procedures are compared. Currently Video Assisted Thoracoscopic
      Surgery (VATS) has gained widespread acceptance in the management of a variety of
      thoracic disorders. It decreases the morbidity and duration of hospital stay. A
      total of 133 children with various thoracic diseases who presented at a
      University Teaching Hospital in the Department of Pediatric Surgery, from June
      2000 to December 2007, were included. Of the 133 patients,116 patients had
      empyema, all of whom were subjected to VATS, and an attempt at
      debridement/decortication and drainage was made. Other thoracic disorders treated
      included lung abscesses, lung biopsies, hydatid cysts, and so on. Patients with
      empyema were treated according to their stage of disease. Of the 116 patients who
      underwent thoracoscopy, 16 had to be converted to open surgery due to various
      reasons. The mean duration for removal of drain was three days and the average
      total duration of hospital stay was six days. Similarly the application of VATS
      was advantageous in other thoracic diseases.

PMID- 20040799
TI  - Video-assisted thoracoscopic surgery in the management of penetrating and blunt
      thoracic trauma.
AB  - BACKGROUND: The role of video-assisted Thoracoscopic Surgery (VATS) is still
      being defined in the management of thoracic trauma. We report our trauma cases
      managed by VATS and review the role of VATS in the management of thoracic trauma.
      MATERIALS AND METHODS: All the trauma patients who underwent VATS from 2000 to
      2007 at Cedars-Sinai Medical Center were retrospectively studied. RESULTS: Twenty
      three trauma patients underwent 25 cases of VATS. The most common indication for
      VATS was retained haemothorax. Thoracotomy was avoided in 21 patients. VATS
      failed in two cases. On an average VATS was performed on trauma day seven (range
      1-26) and the length of hospital stay was 20 days (range 3-58). There was no
      mortality. VATS was performed in an emergency (day 1-2), or in the early (day 2
      7) or late (after day 7) phases of trauma. CONCLUSION: VATS can be performed
      safely for the management of thoracic traumas. VATS can be performed before or
      after thoracotomy and at any stage of trauma. The use of VATS in trauma has a
      trimodal distribution (emergent, early, late), each with different indications.

PMID- 20040800
TI  - Concomitant laparoscopic urological procedures: Does it contribute to morbidity?
AB  - AIM: With advancement in minimal access surgery two laparoscopic procedures can
      be combined together shortening the total hospital stay, decreasing morbidity and
      overall reduced cost. Combining two laparoscopic procedures in a single session
      has been reported in general surgery. Very few articles are available in
      literature with regard to combined urological laparoscopic surgeries. This
      article retrospectively analyses the outcomes of multiple laparoscopic procedures
      performed in a single stage at our centre. MATERIALS AND METHODS: Patients
      undergoing simultaneous procedures from May 2003 to Jan 2009 were included in the
      study. Patients were categorised into three groups according to the primary
      urological organ involved, for better comparison with the control group. Diseases
      involving the adrenals gland were grouped in (group 1), kidney (group 2) and
      renal collecting system/ureter (group 3). All patients had one urological
      procedure for either of the above-mentioned organs combined with another surgical
      procedure. Similarly three control groups were chosen according to the primary
      urological organ involved (group 1c- unilateral laparoscopic adrenalectomy, group
      2c- unilateral laparoscopic radical nephrectomy and group 3c- unilateral
      laparoscopic ureterolithotomy) for comparative study. The operative details,
      hospital stay and complications were analysed. RESULTS: Thirty-two patients
      underwent 64 laparoscopic procedures under single anaesthesia. The most common
      procedure in this series was laparoscopic adrenalectomy (n=34) followed by
      laparoscopic nephrectomy (n=13). Group 1 patients had a prolonged operative time
      ( P=0.012) and hospital stay ( P=0.025) when compared with group 1c. However,
      blood loss was comparable in both the groups. Patients in groups 2 and 3 had
      comparable operative times, blood loss and recovery period with respect to their
      controls. Intraoperatively, the end tidal carbon dioxide levels were within
      permissible limits. All procedures were completed using the laparoscopic
      approach, without any conversion. CONCLUSIONS: Simultaneous laparoscopic
      procedures can be done for urological diseases in selected patients with the
      advantages of single anaesthesia and hospital admission without increasing the
      morbidity.

PMID- 20040801
TI  - Left hepatic vein injury during laparoscopic antireflux surgery for large para
      oesophageal hiatus hernia.
AB  - Although the advent of laparoscopic fundoplication has increased both patient and
      physician acceptance of antireflux surgery, it has become apparent that the
      laparoscopic approach is associated with an increased risk of some complications
      and as well as the occurrence of new complications specific to this approach. One
      such complication occurred in our patient who had intra-operative left hepatic
      vein injury during laparoscopic floppy Nissen fundoplication for large para
      oesophageal rolling hernia. With timely conversion to open procedure, the
      bleeding was controlled and the antireflux and the procedure were completed
      uneventfully. However, this suggests that even with an experience in advanced
      laparoscopy surgery, complications can occur. Clear understanding of the normal
      and pathologic anatomy and its variations facilitates laparoscopic surgery and
      should help the surgeon avoid complications. The incidence of some of these
      complications decreases as surgeons gain experience; however, new complications
      can arise due to the increase in such procedures.

PMID- 20040802
TI  - Laparoscopic approach for very large benign ovarian cyst in young woman.
AB  - Ovarian cysts are the most common cause of pelvic masses in women, and in the
      majority of the cases, women are in their fertile age. Today, the surgical
      treatment has become more conservative and less invasive; hence, a laparoscopic
      approach in the presence of benign cysts has become a gold standard. Herein, we
      report a case of a 21-year-old woman referred to our Surgical Department for an
      abdominal mass, discovered with a computerised tomographic scan, of 20x10 x 25cm
      arising from the left ovary, treated with the laparoscopic approach.

PMID- 20040803
TI  - Laparoscopic splenectomy in a case of blunt abdominal trauma.
AB  - Splenic rupture is a frequent consequence of blunt abdominal trauma. Removal of
      the spleen (splenectomy) or alternative conservative procedures (splenorrhaphy,
      partial splenectomy and haemostatic collagen application) are surgical treatment
      options. Splenectomy was first described in 1910 by Sutherland. Laparoscopic
      splenectomy was first described in 1991 by Delaitre and Maignien. Since then
      significant improvements in instrumentation and technology such as harmonic
      scalpel, endovascular staplers have increased its ease of performance.
      Laparoscopic splenectomy for a ruptured spleen has been reported only in a few
      cases, in which a hand-assisted technique was used. We present the first reported
      case from India (to the best of our knowledge) of a successful removal of a
      ruptured spleen by means of a totally laparoscopic technique.

PMID- 20040804
TI  - Laparoscopic exploration of the common bile duct and removal of dead worm in a
      patient of cholangitis after endoscopic retrograde cholangiopancreatography
      failure.
AB  - We describe a dead ascaris-induced extrahepatic bilary obstruction in a young
      female who presented with acute cholangitis. The dead ascaris was removed by
      laparoscopic exploration of common bile duct after endoscopic retrograde
      cholangiopancreatography failure. Patient had an uneventful hospital course after
      the procedure and was discharged afebrile after 3 days of hospital stay.

PMID- 20040805
TI  - Regional and institutional origin of articles in journal of minimal access
      surgery.

PMID- 20040806
TI  - Laparoscopic approach for irreducible hernia: A consideration.

PMID- 20040807
TI  - Critical care issues in adult liver transplantation.
AB  - Over the last decade, liver transplantation has become an operational reality in
      our part of the world. As a result, clinicians working in an intensive care unit
      are more likely to be exposed to these patients in the immediate postoperative
      period, and thus, it is important that they have a working knowledge of the
      common complications, when they are likely to occur, and how to deal with them.
      The main focus of this review is to address the variety of critical care issues
      in liver transplant recipients and to impress upon the need to provide favorable
      circumstances for the new liver to start functioning and maintain the function of
      other organs to aid in this process.

PMID- 20040808
TI  - Transfusion practice in orthotopic liver transplantation.
AB  - Liver transplant procedures require the most blood components, despite the fact
      that blood use in liver transplantation has declined dramatically over the last
      decade. Liver transplant recipients present unique challenges, not only in terms
      of blood supply, but also requirements for specialized blood components,
      serologic problems, and immunologic effects of transfusion on both the allograft
      and the recipient. The cause of intraoperative blood loss in liver
      transplantation is multifactorial, due to both technical factors and poor
      coagulation control. This procedure carries the risk of massive blood loss, which
      requires massive transfusions and is associated with postoperative infections,
      reduced graft survival, multi-organ dysfunction, and higher risk of mortality.
      Efforts to reduce intraoperative bleeding leading to limitation of blood
      transfusions are desirable to improve results and also to control costs. Method
      of literature search: The name of topic is typed and searched in Google search.
      The name of topic is typed and searched in PubMed search. Related articles were
      also searched. Some standard books in Transfusion Medicine were also referred.

PMID- 20040809
TI  - Amniotic fluid embolism.
AB  - The disastrous entry of amniotic fluid into the maternal circulation leads to
      dramatic sequelae of clinical events, characteristically referred to as Amniotic
      fluid embolism (AFE). The underlying mechanism for AFE is still poorly
      understood. Unfortunately, this situation has very grave maternal and fetal
      consequences. AFE can occur during labor, caesarean section, dilatation and
      evacuation or in the immediate postpartum period. The pathophysiology is believed
      to be immune mediated which affects the respiratory, cardiovascular, neurological
      and hematological systems. Undetected and untreated it culminates into fulminant
      pulmonary edema, intractable convulsions, disseminated intravascular coagulation
      (DIC), malignant arrhythmias and cardiac arrest. Definite diagnosis can be
      confirmed by identification of lanugo, fetal hair and fetal squamous cells
      (squames) in blood aspirated from the right ventricle. Usually the diagnosis is
      made clinically and by exclusion of other causes. The cornerstone of management
      is a multidisciplinary approach with supportive treatment of failing organs
      systems. Despite improved modalities for diagnosing AFE, and better intensive
      care support facilities, the mortality is still high.

PMID- 20040810
TI  - A computer-assisted recording, diagnosis and management of the medically ill
      system for use in the intensive care unit: a preliminary report.
AB  - BACKGROUND: Computerized medical information systems have been popularized over
      the last two decades to improve quality and safety, and for decreasing medical
      errors. AIM: To develop a clinician-friendly computer-based support system in the
      intensive care unit (ICU) that incorporates recording, reminders, alerts,
      checklists and diagnostic differentials for common conditions encountered in
      critical care. MATERIALS AND METHODS: This project was carried out at the Medical
      ICU CMC Hospital, Vellore, in collaboration with the Computer Science Department,
      VIT University. The first phase was to design and develop monitoring and
      medication sheets. Terminologies such as checklists (intervention list that pops
      up at defined times for all patients), reminders (intervention unique to each
      patient) and alerts (time-based, value-based, trend-based) were defined. The
      diagnostic and intervention bundles were characterized in the second phase. The
      accuracy and reliability of the software to generate alerts, reminders and
      diagnoses was tested in the third phase. The fourth phase will be to integrate
      this with the hospital information system and the bedside monitors. RESULTS:
      Alpha testing was performed using six scenarios written by intensivists. The
      software generated real-time alerts and reminders and provided diagnostic
      differentials relevant to critical care. Predefined interventions for each
      diagnostic possibility appeared as pop-ups. Problems identified during alpha
      testing were rectified prior to beta testing. CONCLUSIONS: The use of a computer
      assisted monitoring, recording and diagnostic system appears promising. It is
      envisaged that further software refinements following beta testing would
      facilitate the improvement of quality and safety in the critical care
      environment.

PMID- 20040811
TI  - Role of steroids in septic shock: assessment of knowledge, attitudes and
      practices among intensivists practising in Hyderabad.
AB  - CONTEXT: Use of steroids in septic shock is an issue of contention, more so with
      two major trials reporting conflicting results. AIMS: To assess the current
      knowledge, attitudes and practices (KAP) related to the role of steroids in
      septic shock among intensivists practising in Hyderabad. SETTING, DESIGN,
      MATERIALS AND METHODS: Questionnaires containing 10 questions pertaining to the
      role of steroids in septic shock, were distributed to 76 intensivists during the
      monthly critical care meeting. RESULTS: A great majority of intensivists (82%)
      agreed that the role of steroids is restricted to septic shock not responding to
      vasopressors. There was no clear consensus regarding the role of corticotropin
      stimulation test or the timing of total cortisol level testing, if it has to be
      performed. Hydrocortisone was clearly the choice of steroid for most intensivists
      and intravenous bolus injection being the preferred route of administration.
      There was no agreement regarding the dose of steroids, the role of
      fludrocortisone and whether steroids should be tapered. Most of the respondents
      did not extend the steroid therapy beyond seven days and the most common side
      effect reported was hyperglycemia. CONCLUSION: There is a lot of ambiguity in the
      knowledge, attitudes or practices regarding role of steroids in septic shock
      among intensivists in Hyderabad. Uniform policies and protocols need to be
      devised at institutional level, with multispecialty inputs, and doctors need to
      be familiarized accordingly.

PMID- 20040812
TI  - Antibiotic sensitivity pattern of gram negative bacilli isolated from the lower
      respiratory tract of ventilated patients in the Intensive care unit.
AB  - BACKGROUND: Lower respiratory tract infections (LRTIs) are the most frequent
      infections among patients in Intensive care units (ICUs). AIMS: To know the
      bacterial profile and determine the antibiotic susceptibility pattern of the
      lower respiratory tract isolates from patients admitted to the ICU. SETTINGS AND
      DESIGN: Tertiary care hospital, retrospective study. MATERIALS AND METHODS:
      Transtracheal or bronchial aspirates from 207 patients admitted to the ICU were
      cultured, identified, and antibiotic sensitivity was performed by standard
      methods. STATISTICAL ANALYSIS USED: SPSS software was used for calculation of % R
      of 95% confidence interval (CI). RESULTS: Of 207 specimens, 144 (69.5%) were
      culture positive and 63 (30.4%) showed no growth. From 144 culture positives, 161
      isolates were recovered, of which 154 (95.6%) were Gram negative bacilli (GNB).
      In 17 (11.0%) patients, two isolates per specimen were recovered. The most common
      GNB in order of frequency were Pseudomonas aeruginosa (35%), Acinetobacter
      baumannii (23.6%), and Klebsiella pneumoniae (13.6%). A very high rate of
      resistance (80-100%) was observed among predominant GNB to ciprofloxacin,
      ceftazidime, co-trimoxazole, and amoxycillin/clavulanic acid combination. Least
      resistance was noted to meropenem and doxycycline. CONCLUSION: Nonfermenters are
      the most common etiological agents of LRTIs in ICU. There is an alarmingly high
      rate of resistance to cephalosporin and beta-lactam-beta-lactamase inhibitor
      group of drugs. Meropenem was found to be the most sensitive drug against all
      GNB. Acinetobacter and Klebsiella spp. showed good sensitivity to doxycycline.

PMID- 20040813
TI  - Pattern and outcome of acute poisoning cases in a tertiary care hospital in
      Karnataka, India.
AB  - BACKGROUND AND OBJECTIVE: Acute poisoning is a medical emergency. It is important
      to know the nature, severity and outcome of acute poisoning cases in order to
      take up appropriate planning, prevention and management techniques. This study
      aimed to assess the pattern and outcome of acute poisoning cases in a tertiary
      care hospital in Karnataka. MATERIALS AND METHODS: This is a retrospective
      hospital record-based study conducted in a tertiary care hospital attached to a
      medical institution in Karnataka. The study included 136 cases and data regarding
      age, sex, time elapsed after intake; circumstances of poisoning, name of the
      poisonous substance, chemical type, duration of hospitalization, severity and
      outcome were collected in the prestructured proforma. RESULTS: Incidence was more
      common among males (75.4%) compared to females (24.3). Most cases of acute
      poisoning presented among 20- to 29-year age group (31.2%) followed by 12- to 19
      year age group (30.2%). A majority of poisoning cases (36.0%) were due to
      organophosphorus compound (OPC). Total mortality was found to be 15.4%. Mortality
      rate due to corrosives was significantly high compared with OPC poisoning (chi(2)
      = 4.12, P = 0.04). Of the 56 patients of OPC and carbamate poisoning, 13 patients
      (23.2%) had respiratory arrest and required respiratory support. Time lapse had a
      significant role on the mortality in cases of acute poisoning (chi(2) = 10.9, P =
      0.01). CONCLUSION: Poisoning is more common in young males. The overall mortality
      is substantially high, mainly contributed by self-poisoning with insecticides and
      corrosives. Early care in a tertiary care center may help to reduce mortality in
      India.

PMID- 20040814
TI  - Prevalence and antimicrobial susceptibility pattern of methicillin-resistant
      Staphylococcus aureus in Assam.
AB  - AIMS: Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious
      problem in intensive care units, because of development of multiresistance, and
      also intrinsic resistance to beta-lactam antibiotics. The present study was
      carried out to investigate the prevalence of MRSA and their rate of resistance to
      different antistaphylococcal antibiotics. MATERIALS AND METHODS: Between January
      2007 and February 2008, the clinical specimens submitted at the microbiology
      laboratory were processed and all S. aureus isolates were included in this study.
      All isolates were identified morphologically and biochemically by standard
      laboratory procedures and antibiotic susceptibility pattern was determined by
      modified Kirby Bauer disc diffusion method. RESULTS: Methicillin resistance was
      observed in 34.78% of isolates, of which 37.5% were found to be resistant to all
      commonly used antibiotics. In MRSA isolates, 50% had constitutive resistance,
      9.38% had inducible MLS(B) resistance and 18.75% had MS phenotype. CONCLUSIONS:
      There is a progressive increase in MRSA prevalence in the country but the present
      rate is still low in comparison to values found in some other institutes. The
      rate of inducible MLS(B) resistance was also lower in comparison with findings
      from other parts of the country.

PMID- 20040815
TI  - How correct is the correct length for central venous catheter insertion.
AB  - BACKGROUND AND AIM: Central venous catheters (CVC) are important in the
      management of critically ill patients. Incorrect positioning may lead to many
      serious complications. Chest radiograph is a convenient means of determining the
      correct position of the catheter tip. The present study was designed to evaluate
      the depth of CVC placed through the right and left internal jugular vein (IJV) in
      order to achieve optimum placement of the catheter tip. MATERIALS AND METHODS: A
      total of 107 patients in whom CVCs were put through either the right or left IJV
      through a central approach were included in this prospective study. Catheter tip
      position was observed in the post procedure chest radiograph. It was considered
      correct if the tip was just below the carina in the left-sided catheters and just
      above carina in the right-sided catheters. The catheters were repositioned based
      on the chest radiographs. The catheter depth leading to optimum tip placement was
      noted. RESULTS: In males, catheter repositioning was required in 13 of 58
      patients (22.41%) in the right IJV catheters, whereas in 2 of 13 patients
      (15.38%) in the left IJV catheters. In females, repositioning was required in 12
      of 25 patients (48%) in the right IJV catheters and 2 of 11 patients (18.18%) in
      the left IJV catheters. Repositioning rate was higher in females (14/36) compared
      with males (15/71), which was statistically significant (P = 0.05, 95% CI).
      Repositioning rates were significantly higher in females (12/25) as compared with
      males (13/58) in the right IJV catheters (P = 0.019, 95% CI). CONCLUSION: By
      cannulating the IJV through a central approach, the catheters can be fixed at a
      length of 12-13 cm in males and 11-12 cm in females in the right IJV and at a
      length of 13-14 cm in males and 12-13 cm in females in the left IJV in order to
      achieve correct positioning.

PMID- 20040816
TI  - Concurrent administration of heparin and activated protein C in a patient with
      pulmonary embolism and severe sepsis with positive outcome.
AB  - Results of the PROWESS trial suggested that heparin may reduce the efficacy of
      recombinant human activated protein C (rhAPC) and the XPRESS study also showed
      increased bleeding complications in patients receiving heparin with rhAPC.
      Although it has been shown that heparin prophylaxis may be used along with rhAPC,
      no study has shown the interaction between continuous heparin infusion and rhAPC.
      Here, we report a case of severe sepsis with pulmonary embolism who was
      concurrently administered heparin and rhAPC infusions, with positive results and
      no bleeding complications.

PMID- 20040817
TI  - Vincristine-induced acute life-threatening hyponatremia resulting in seizure and
      coma.
AB  - We report a case of a four-year-old boy with stage 1 Wilms tumour, who developed
      Vincristine-induced acute life- threatening hyponatremia, which presented as
      generalized tonic clonic seizures and coma. He was intubated and mechanically
      ventilated. There were no localizing neurological signs. CSF study showed no
      cells and CSF proteins were 20 mg%. Electrocardiography, chest X-ray,
      echocardiography, CT scan and liver function tests were normal. Evaluation of
      electrolytes and arterial blood gas showed serum sodium of 113 mEq/L with mild
      metabolic acidosis. Serum osmolality was 260 mOsm/L (normal value 285-295 mOsm/L)
      and urine osmolality was 625 mOsm/L (normal range 300-900 mOsm/L), urine sodium
      280 mEq/d (normal range 100-260 mEq/d), serum potassium, blood urea, blood sugars
      were normal. Serial blood cultures showed no bacterial growth. Patient was
      treated with fluid restriction, hypertonic saline (3%) and other supportive care.
      Patient improved clinically over three days and was extubated on the third day
      and shifted to the ward on the fifth day.

PMID- 20040818
TI  - Accidental carbon monoxide poisoning in our homes.
AB  - Carbon monoxide (CO) is a colorless, odorless, tasteless, nonirritating, but
      significantly toxic gas. It is a product of combustion of organic matter in
      presence of insufficient oxygen supply. Symptoms of mild poisoning include
      headaches, vertigo and flu like effects, whereas larger exposures can lead to
      significant toxicity of the central nervous system (CNS), heart, and even death.
      We are reporting two cases that presented to us in the winter months of December
      to January with history, sign, symptoms, and radiological evidence of suspected
      CO poisoning.

PMID- 20040819
TI  - Aluminum phosphide poisoning.

PMID- 20040820
TI  - In this issue/abstract thinking: new findings in developmental research with
      animals.

PMID- 20040821
TI  - How continua converge in nature: cognition, social competence, and autistic
      syndromes.

PMID- 20040822
TI  - Pharmacotherapy of pediatric insomnia.

PMID- 20040823
TI  - Motivational interviewing and adolescent psychopharmacology.

PMID- 20040824
TI  - Safety and tolerability of atomoxetine over 3 to 4 years in children and
      adolescents with ADHD.
AB  - OBJECTIVE: To assess the long-term safety and tolerability of atomoxetine
      hydrochloride in children and adolescents with attention-deficit/hyperactivity
      disorder treated for > or = 3 years. METHOD: Data from 13 double-blind, placebo
      controlled trials and 3 open-label extension studies were pooled. Outcome
      measures were patient-reported treatment-emergent adverse events (AEs);
      discontinuations due to AEs, serious AEs, and changes in body weight, height,
      vital signs, electrocardiogram, and hepatic function tests. RESULTS: In total,
      714 patients were treated with atomoxetine for > or = 3 years (mean follow-up 4.8
      years [SD 1.1 years]), including a subset of 508 treated for > or = 4 years (mean
      follow-up 5.3 years [SD 0.8 years]). Most subjects were younger than 12 years at
      entry (73.8%), male (78.4%), and white (88.9%). The mean final daily dose of
      atomoxetine was 1.35 mg/kg (SD 0.37 mg/kg). No new or unexpected AEs were
      observed compared with acute-phase treatment. Less than 6% of patients exhibited
      aggressive/hostile behaviors, and less than 1.6% reported suicidal
      ideation/behavior. No clinically significant effects were seen on growth rate,
      vital signs, or electrocardiographic parameters, and < or = 2% of patients showed
      potentially clinically significant hepatic changes. CONCLUSION: Atomoxetine was
      safe and well tolerated for children and adolescents with > or = 3 and/or > or =
      4 years of treatment.

PMID- 20040825
TI  - Magnetic resonance simulation is effective in reducing anxiety related to
      magnetic resonance scanning in children.

PMID- 20040826
TI  - Practice parameter for the psychiatric assessment and management of physically
      ill children and adolescents.
AB  - This practice parameter describes the psychiatric assessment and management of
      physically ill children and adolescents. It reviews the epidemiology, clinical
      presentation, assessment, and treatment of psychiatric symptoms in children and
      adolescents with physical illnesses and the environmental and social influences
      that can affect patient outcome.

PMID- 20040828
TI  - Guest editorial: accessible and affordable hearing health care for adults with
      mild to moderate hearing loss.

PMID- 20040829
TI  - The participation of Hans Hinselmann in medical experiments at Auschwitz.
AB  - A medical experiment of precancerous screenings of the cervix with colposcopy
      involving Jewish inmates was conducted in 1943 at Auschwitz by Eduard Wirths, the
      chief camp physician (SS-Standortarzt), his brother, Helmut Wirths, gynecologist
      of Hamburg-Altona with the complicity of the prestigious professor Hans
      Hinselmann who developed the colposcope. This medical experiment illustrates the
      relationships between physicians carrying out experiments at Auschwitz and
      prestigious medical research of the most reputed German universities. Hans
      Hinselmann should be remembered as complicit with atrocities and should not
      continue to be honored. Physicians must know what tortures and atrocities were
      committed for the promotion of the development of colposcopy.

PMID- 20040831
TI  - The optimum organization for the delivery of colposcopy service in Ontario: a
      systematic review.
AB  - OBJECTIVE: To determine the optimum organization for colposcopy service delivery
      in Ontario, Canada. METHODS: A multidisciplinary expert panel was convened to
      develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE,
      CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to
      February 2006 for articles that reported guidance or outcomes relating to
      improved outcomes in colposcopy training, qualifications, accreditation,
      maintenance of competency, the delivery of colposcopy, reducing default from
      colposcopy clinics, and/or strategies to improve patient satisfaction or comfort.
      In addition, an environmental scan identified unpublished documents related to
      the delivery of colposcopy services. RESULTS: Sixteen guidance documents related
      to the delivery of colposcopy services were identified; 5 from the published
      literature and 11 from the environmental scan. These documents were used by the
      panel to inform the systematic review and companion guidelines. CONCLUSIONS:
      Overall, the Ontario Colposcopy Guidelines Development Group believes that the
      benefits associated with the implementation of colposcopy recommendations in
      Ontario will result in greater organization of care and improved patient
      outcomes. In addition, the group anticipates that these recommendations will
      provide useful guidance to regional planning authorities, hospital
      administrators, and Cancer Care Ontario, as well as colposcopists and other
      practitioners, in the planning of integrated regional and provincial cancer
      screening services.

PMID- 20040830
TI  - Digital assessment of the reproductive tract versus colposcopy for directing
      biopsies in women with abnormal Pap smears.
AB  - OBJECTIVE: This study aimed to compare digital camera assessment of the
      reproductive tract (DART) to colposcopy for the evaluation of abnormal Pap
      smears. MATERIALS AND METHODS: Participants included 207 women with abnormal Pap
      smears. Colposcopy and DART were performed on each patient by separate examiners
      with the goal of lesion detection. Analysis was performed per patient and per
      biopsy. RESULTS: Patients had an average of 2.9 biopsies. Forty-two patients and
      81 biopsies were positive for cervical intraepithelial neoplasia 2+. Both DART
      and colposcopy detected 41 (97.6%) of 42 patients (95% CI = 85.9%-99.9%). Digital
      camera assessment of the reproductive tract detected 66/81 (81.4%; CI = 70.7%
      88.9%) and colposcopy detected 69/81 (85.2%; CI = 73.2%-92.4%) of biopsies that
      were cervical intraepithelial neoplasia 2+. CONCLUSIONS: Digital camera
      assessment of the reproductive tract detects high-grade lesions of the cervix
      with similar sensitivity to colposcopy. It holds great promise to expand cervical
      cancer precursor lesion detection in areas with limited resources.

PMID- 20040832
TI  - Lubricant, mucus, and other contaminant materials as a potential source of
      interpretation errors in ThinPrep cervical cytology.
AB  - OBJECTIVE: To investigate the possibility of the occurrence of errors in the
      interpretation of cervical smears in the presence of lubricant, mucus and other
      contaminant particles in ThinPrep (TP) technique (Cytyc Corp., Boxborough, MA)
      liquid-based cervical cytology. MATERIALS AND METHODS: Four thousands sixty-eight
      TP cervical smears were reviewed over a 12-month period. Those cases that
      initially had caused interpretation errors in which lubricant, mucus, and other
      contaminant materials were confused with infectious agents or epithelial
      abnormalities among the primary screening cytotechnologists and pathologists were
      selected for our study. These cases were retrieved from the cytology unit's
      registered logbook. The possibility of these detected lubricant, mucus, and other
      contaminant materials in these cases to cause misinterpretation for randomly
      selected pathologists and cytotechnologists who were blinded for the study was
      further investigated. Three cytotechnologists and 2 pathologists were
      independently asked to give their opinions on each case without their prior
      knowledge of the selected cases. RESULTS: Only 15 cases out of 4068 were found to
      cause interpretation errors. Five different contaminant patterns were detected.
      The main potential misinterpretations included secondary diagnosis that is
      confused mainly with infectious agents. However, other contaminants were even
      misinterpreted as high-grade squamous epithelial abnormalities. CONCLUSIONS: This
      study illustrates the potential of lubricant, mucus, and foreign body contaminant
      materials to cause interpretation errors in TP cervical cytology. Although liquid
      based preparation reduces the obscuring effect of these materials, the unusual
      appearance of some of these particles in TP cervical smears not only can mimic
      infectious microorganisms, but also squamous dyskaryosis. This can lead to
      serious interpretation errors for the inexperienced cytotechnologists and
      pathologists, which subsequently can have an effect on the women's management.

PMID- 20040833
TI  - Incidence and costs of cervical intraepithelial neoplasia in a US commercially
      insured population.
AB  - OBJECTIVE: This study aimed to estimate incidence, cost per episode of care, and
      US population burden of cervical intraepithelial neoplasia (CIN). MATERIALS AND
      METHODS: For women continuously enrolled in a US health plan from January 1, 1999
      to December 31, 2004, medical claims were used to identify potential CIN
      diagnosis. Presence and grade of CIN (CIN 1, CIN 2,3, or no CIN) were verified in
      medical records for a randomly selected subset (n = 254). Incidence, costs, and
      population burden were calculated. RESULTS: Annual incidence for CIN 1 and CIN
      2,3 was 1.6 and 1.2 per 1,000 women, respectively. Incidence was highest among
      women aged 21 to 30 years (3.3 and 3.6 per 1,000) and women aged 31 to 40 years
      (2.9 and 2.7 per 1,000). Costs per episode of care were higher for CIN 2,3
      ($1,634 vs $1,084). Estimated annual burden per 1,000 US women was $1,059 for CIN
      1 and $1,803 for CIN 2,3. CONCLUSIONS: We estimate that 412,000 women in the
      United States are diagnosed with CIN annually, with an associated cost of
      approximately $570 million.

PMID- 20040834
TI  - Depot medroxyprogesterone acetate: a risk factor for cervical stenosis after loop
      electrosurgical excisional procedure management of cervical intraepithelial
      neoplasia?
AB  - OBJECTIVES: In our anecdotal experience and sporadically in the literature,
      gynecologists have observed a connection between patient's use of depot
      medroxyprogesterone acetate (DMPA) and increased occurrence of cervical stenosis
      during follow-up after loop electrosurgical excisional procedure (LEEP). We
      decided to formally examine this association in our clinic population. MATERIALS
      AND METHODS: We performed a chart review, enrolling 257 patients and tabulating
      data on demography, use of hormonal contraceptives, characteristics of the LEEP,
      and presence or absence of cervical stenosis at 1- and 6-month follow-up
      evaluations. Univariate tests of association between the independent variables
      and the dependent variable of cervical stenosis were examined via the chi and
      Student t tests for discrete and continuous variables, respectively. To
      characterize the relative importance of independent variables significantly
      associated with cervical stenosis, logistic regression was performed. RESULTS: Of
      the 257 charts reviewed, 127 patients (49.4%) completed 1 and 6 months after LEEP
      follow-up appointments, providing adequate data for analysis. In this population,
      we observed 25 cases of cervical stenosis, or an overall rate of 19.7%. Of
      patients using DMPA at the time of LEEP or during the follow-up period, 9 (41.0%)
      of 22 developed stenosis, whereas of those who did not use DMPA, 16 (15.2%) of
      105 developed stenosis, indicating a significant difference (odds ratio = 3.85,
      95% CI = 1.41-10.50). CONCLUSIONS: In our clinic population, use of DMPA was
      associated with higher rates of development of cervical stenosis, calling for
      larger studies of the association of DMPA in this LEEP complication.

PMID- 20040835
TI  - Opinions of parents about school-entry mandates for the human papillomavirus
      vaccine.
AB  - OBJECTIVE: To determine parents' opinions about school-entry mandates for the
      human papillomavirus (HPV) vaccine. MATERIALS AND METHODS: During the summer of
      2008, 325 parents, with children 9 to 17 years old, completed a 53-question
      survey that evaluated their opinions about vaccines, HPV and the HPV vaccine, and
      mandatory childhood vaccination programs. Descriptive statistics were calculated
      for all survey items. RESULTS: Although 89% of parents supported mandatory
      vaccination programs in general, only 43% thought that the HPV vaccine should be
      included. The main reasons for nonsupport included that it would infringe on
      their rights (57%), that the vaccine had not been well studied (33%), and that it
      had too many adverse effects (29%). Of all parents, 13% said their children had
      already received the HPV vaccine and 81% wanted their children to receive it.
      CONCLUSIONS: At this point, although most parents want their children to receive
      the HPV vaccine, most do not support it being mandated. The provision of more
      safety data to parents should help improve overall HPV vaccination rates.

PMID- 20040836
TI  - Colposcopic characteristics of high-risk human papillomavirus-related cervical
      lesions.
AB  - OBJECTIVE: Because high-risk human papillomavirus (hrHPV) is the necessary factor
      in the development of high-grade cervical lesions, knowing the colposcopic
      differences between hrHPV-positive and hrHPV-negative lesions could be of value.
      We have evaluated whether there are colposcopic differences between lesions
      testing hrHPV-positive or hrHPV-negative. MATERIALS AND METHODS: This study was
      conducted as a retrospective case-control study. We designed a scoring system for
      colposcopic criteria that might be of relevance to distinguish hrHPV-positive
      from hrHPV-negative lesions. Colposcopic images were analyzed from patients at
      the VU University Medical Center Amsterdam, the Netherlands, in whom a GP5+/6+
      polymerase chain reaction hrHPV test had been performed within a month of the
      colposcopic examination (n = 507). RESULTS: Visibility of the transformation zone
      (corrected for age), a (very) coarse and irregular punctation pattern, and a
      large lesion (>25% of the visible cervix) were more often associated with a
      positive hrHPV test status (p =.001, odds ratio [OR] = 2.29, 95% CI = 1.41-3.73;
      p =.036, OR 2.37, 95% CI = 1.08-5.19; and p =.044, OR = 1.78, 95% CI = 1.08-2.94,
      respectively). After correction for histologic diagnosis, the difference between
      hrHPV-positive and hrHPV-negative lesions for visibility of the transformation
      zone and lesion size remained statistically significant (OR = 2.44, 95% CI = 1.35
      4.41 and OR = 1.92, 95% CI = 1.04-3.54, respectively). CONCLUSIONS: This study
      indicates that visibility of the transformation zone, (very) coarse punctation
      pattern, and larger lesion size were the main colposcopic features associated
      with a hrHPV-positive test status.

PMID- 20040837
TI  - Case series of Zoon vulvitis.
AB  - We report 3 cases of plasma cell vulvitis (Zoon vulvitis) over a 10-year period
      and their management. This series highlights 1 case that was refractory to all
      modalities of treatment and hence had to be managed surgically, which has only
      been reported once before.

PMID- 20040838
TI  - Peripheral neuroectodermal tumor of the vulva: a case report.
AB  - BACKGROUND: Peripheral neuroectodermal tumors arising from vulva are extremely
      rare; only 12 cases have been reported so far. These tumors belong to the Ewing
      sarcoma family of tumors. They occur in bones and variety of soft tissues of
      chest wall, pelvis, paravertebral region, and lower extremities. Being aggressive
      tumors, they have poor prognosis. CASE: We report a case of a 20-year-old woman
      who presented with a 20 x 15 x 10-cm pedunculated mass arising from the right
      labium majus. Judicious use of a panel of markers led to diagnosis of peripheral
      neuroectodermal tumor. The patient died of metastatic disease. CONCLUSIONS:
      Judicious use of a panel of markers and a molecular test, if necessary, helps in
      confirming the diagnosis. Surgery followed by chemotherapy with or without
      radiation is the treatment of choice.

PMID- 20040839
TI  - Chronic lymphocytic leukemia presenting with localized gynecologic symptoms.
AB  - BACKGROUND: Although no cure exists for chronic lymphocytic leukemia (CLL),
      treatment can reduce morbidity and/or improve survival in advanced disease.
      Identification of patients in an early disease state allows monitoring and
      treatment as soon as appropriate. We were unable to find previous reports of
      early CLL disease presenting with gynecologic symptoms. This report seeks to
      alert gynecologists of their potential role in identifying CLL patients. CASE: A
      76-year-old woman presented with rectovaginal pressure. Cervical cone biopsy
      showed a lymphoproliferative process. Peripheral blood flow cytometry confirmed a
      diagnosis of early-stage CLL. The patient remains asymptomatic and is currently
      monitored for disease progression. CONCLUSION: Early CLL can present with
      localized gynecologic symptoms or cervical lesions. The recognition of early
      disease can assure optimal treatment.

PMID- 20040840
TI  - Chronic vulvar fissure--a rare manifestation of mycosis fungoides.
AB  - BACKGROUND: Vulvar fissures are a common cause of vulvar pain and discomfort. The
      differential diagnosis of the underlying process is broad, and some cases remain
      undiagnosed. Mycosis fungoides, the dominant component of cutaneous T-cell
      lymphoma, rarely present as fissures. We report a case of a chronic vulvar
      fissure due to mycosis fungoides. CASE: A 55-year-old woman was referred to the
      vaginitis clinic for evaluation of a chronic vulvar fissure, 6 cm in length,
      located at the left interlabial sulcus. A detailed history and examination for
      other skin lesions revealed an erythematous pruritic patch on left breast that
      had been present for years. Repeat biopsies from both sites showed a dense dermal
      lymphocytic infiltrate composed predominantly of CD3- and CD4-positive T cell
      with minimal epidermotropism. A T-gamma polymerase chain reaction analysis
      demonstrated a clonal T-cell rearrangement. Based on a diagnostic algorithm that
      combines clinical features, histopathology, and molecular biology, a diagnosis of
      mycosis fungoides was confirmed. CONCLUSIONS: Patients presenting with vulvar
      lesions should always be suspected of having an underlying dermatosis, and a
      detailed examination for other skin lesions should be performed. In the presented
      case, once both skin lesions were linked clinically, repeat biopsies of both
      sites led to a confirmed diagnosis of mycosis fungoides.

PMID- 20040841
TI  - Home Study Course: winter 2010.

PMID- 20040842
TI  - Don't stop thinking about tomorrow--yesterday's gone.

PMID- 20040845
TI  - Comparison of the prognostic value of inflammation-based pathologic and
      biochemical criteria in patients undergoing potentially curative resection for
      colorectal cancer.

PMID- 20040846
TI  - Should laparoscopic cholecystectomy be practiced in the developing world?

PMID- 20040849
TI  - Preoperative transarterial chemoembolization for resectable large hepatocellular
      carcinoma.

PMID- 20040850
TI  - Keeping an open (surgery) mind.

PMID- 20040851
TI  - National health care expenditures: addressing the cost of health care in the
      United States.

PMID- 20040852
TI  - Health care reform: are we missing the important issues?

PMID- 20040853
TI  - Evaluation of the cost-effectiveness of cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy (peritonectomy) at the St George Hospital peritoneal
      surface malignancy program.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) are treatment approaches for peritoneal carcinomatosis that
      has demonstrated improved survival outcomes with acceptable complication rates.
      This report aims to measure and describe the survival outcomes and health care
      cost associated with CRS and HIPEC for peritoneal surface malignancies at a
      centralized tertiary institution in Australia. METHODS: The expenditure of
      treatment for 136 consecutive patients who underwent 159 CRS and HIPEC from June
      2002 to June 2008 were obtained. Together with their survival outcomes from
      treatment, a cost-effectiveness analysis was performed. RESULTS: The average cost
      of CRS and HIPEC per patient and per life year for appendix cancer is AUD $88,423
      (range, AUD $23,933-AUD $299,145) and AUD $37,737/LY; for colorectal cancer is
      AUD $66,148 (range, AUD $26,079-AUD $409,666) and AUD $29,757/LY; for
      pseudomyxoma peritonei is AUD $92,308 (range, AUD $11,562-AUD $501,144) and AUD
      $29,559/LY; for peritoneal mesothelioma is AUD $55,062 (range, AUD $23,261-AUD
      $94,104) and AUD $20,521/LY; and for other peritoneal surface malignancies is AUD
      $44,668 (range, AUD $31,592-AUD $70,026) and AUD $22,091/LY. CONCLUSIONS: This
      complex surgical treatment results in significant increases in medical costs with
      a parallel increase in survival for a disease that has been poorly treated, and
      hence may be considered as cost-effective given the observed life years gained.

PMID- 20040854
TI  - The learning curve for the laparoscopic approach to conservative mesorectal
      excision for rectal cancer: lessons drawn from a single institution's experience.
AB  - OBJECTIVES: We aimed to determine the most sensitive markers of the learning
      process for laparoscopic conservative mesorectal excision (LCME) for rectal
      cancer to (1) generate a relevant training program for junior surgeons and (2)
      define appropriate settings for prospective trials. SUMMARY BACKGROUND DATA: The
      learning process for the laparoscopic approach to treating rectal cancer has not
      yet been clearly described. METHODS: Over a 42-month period, 127 patients
      received LCME at our institution. The procedure was performed or supervised by a
      single referent surgeon. The operative time, conversion to open procedure
      postoperative morbidity, microscopic margins, and local recurrence were thought
      to be the most relevant parameters related to the learning process. To give a
      comprehensive view of success, a single hybrid variable was generated. Curves
      were drawn using the moving average method for continuous variables and the CUSUM
      analysis was used for binary variables. RESULTS: A slow but continuous decrease
      in operative time was observed over all the study period. The overall and
      surgical morbidities were the most sensitive markers. The conversion rate and R0
      resection rate remained stable at 14.9% and 91%, respectively. The overall local
      recurrence rate was 4.7% at a median follow-up time of 40 months and was not
      affected by the learning process. The success rate reached a steady state after
      50 patients. CONCLUSION: Despite surgeons' early command of the conversion rate,
      the learning process for LCME affects morbidity for the first 50 patients
      operated on, but does not adversely affect the oncological results. Much emphasis
      should therefore be placed on technical training.

PMID- 20040855
TI  - Algorithm-based coagulation management of catastrophic amniotic fluid embolism.
AB  - Amniotic fluid embolism (AFE) is a rare, but often catastrophic, complication of
      pregnancy and associated with severe coagulopathy. We present an algorithm-based
      approach in managing coagulopathy and hemorrhage in a fatal case of
      histopathologically proven AFE. Thrombelastometry was used for rapid evaluation
      of the coagulation status. Stop of extensive hyperfibrinolysis with tranexamic
      acid, stabilization of initial clot formation with high-dose fibrinogen and
      platelet transfusions, and use of prothrombin complex concentrate together with a
      1: 1 transfusion regimen of red packed cells and fresh frozen plasma was
      successful to control diffuse bleeding and restore clot firmness after
      hysterectomy. Stable clotting situation was maintained despite further clinical
      deterioration and development of multiple organ failure in this patient.

PMID- 20040856
TI  - Low plasma concentrations of coagulation factors II, VII and XI indicate
      increased risk among elderly with symptoms of heart failure.
AB  - Heart failure is a serious condition, and it is, therefore, important to identify
      patients at high risk as early as possible in order to initiate appropriate
      treatment. The condition results in complicated disease mechanisms including
      disturbances in blood coagulation. The aim of the present study was to evaluate
      whether low plasma concentrations of coagulation factors (F) II, VII and XI
      influence cardiovascular mortality in an elderly population with possible heart
      failure. A cardiologist evaluated 450 elderly patients who attended primary
      healthcare because of symptoms associated with heart failure. He recorded new
      patient history, conducted a clinical examination, took blood samples, determined
      concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed
      Doppler echocardiography. The patients were followed over almost a 10-year period
      during which all mortality was registered. In patients with suspected heart
      failure, those with low plasma concentrations of FII, FVII, FXI or all had a
      significantly higher mortality rate during the follow-up period of 10 years as
      compared with those with higher plasma concentrations, in contrast with findings
      in previous reports on patients with acute coronary syndromes. In the group with
      a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or
      all, the risk of cardiovascular mortality increased two to three times.

PMID- 20040857
TI  - Asymptomatic factor VII deficiency: gene analysis and structure-function
      relationships.
AB  - Factor VII Padua is a variant form of factor VII deficiency characterized by a
      prolongation of the prothrombin time (PT), when the assay is performed using
      rabbit brain thromboplastin. The PT is normal when performed using either human
      or ox brain thromboplastin reagents, or a recombinant human tissue factor-based
      thromboplastin. We report a case of an African-American woman with asymptomatic
      factor VII deficiency, who had a prolonged PT and factor VII activity levels of 5
      8% using rabbit brain thromboplastin, but a normal PT and factor VII activity
      levels when measured using recombinant human brain thromboplastin or tissue
      factor. The amino acid substitution (R304Q), which gives rise to factor VII
      Padua, was found in our patient, making this only the fourth African-American
      case described to date with this mutation. Our report emphasizes the importance
      of identifying this benign form of factor VII deficiency in order to avoid
      unnecessary exposure of patients to treatment with either plasma-derived products
      or recombinant activated factor VII.

PMID- 20040858
TI  - Natural anticoagulant protein levels in Turkish patients with inflammatory bowel
      disease.
AB  - Thromboembolism is an important cause of morbidity and mortality in patients with
      inflammatory bowel disease (IBD). The aim of this study was to investigate common
      thrombophilic markers in patients with IBD and to search for a relation between
      these predisposing factors and activity of disease. Seventy-four patients with
      ulcerative colitis, 22 patients with Crohn's disease and 20 healthy volunteers
      were enrolled into the study. Plasma levels of protein C, protein S, antithrombin
      III and activated protein C resistance were determined in patients with IBD and
      healthy controls. Mean values of protein C, protein S and antithrombin III were
      significantly lower in patients with ulcerative colitis and Crohn's disease
      compared with the healthy control group. Patients with active ulcerative colitis
      had lower protein C, protein S and antithrombin III level than patients in
      remission (P < 0.001, P < 0.001, P < 0.001). Levels of protein C, S and
      antithrombin III were also decreased in patients with active Crohn's disease
      compared with those in remission (P < 0.05, P < 0.001, P < 0.05). Differences in
      all natural anticoagulant levels between patients in remission and healthy
      individuals in both ulcerative colitis and Crohn's disease groups were not
      statistically significant (P > 0.05). No significant difference was observed in
      activated protein C resistance (APCR) between patients with active disease, those
      in remission and the control group (P > 0.05). Abnormalities in natural
      anticoagulants are common in patients with IBD during active disease.

PMID- 20040859
TI  - Acquired hemophilia A: three different presentations of the same disease.
AB  - Acquired hemophilia A is a rare disorder characterized by the presence of an
      autoantibody (mainly immunoglobulin G) to the clotting factor VIII with a
      clinical resemblance to hemophilia A. This autoantibody may arise because of
      dysregulation of the immune system. It is associated with various autoimmune or
      dermatologic diseases, pregnancy, or drug ingestion, but in almost 50% patients,
      the cause is unknown. In the present study, we have reported three different
      clinical presentations of acquired hemophilia. In two cases, the underlying
      disorder was the probable respiratory chronic disease (asthma), and in the other,
      it was idiopathic. We reviewed the response to a given treatment. The severity of
      the clinical presentation was different in all the cases, and was taken into
      account when we decided on the best course of treatment. The present report
      presents two patients successfully treated with a tapering course of steroids,
      and one with the anti-CD20 monoclonal antibody not given as first line treatment.

PMID- 20040860
TI  - Selenium and glutamine supplements: where are we heading? A critical care
      perspective.
AB  - PURPOSE OF REVIEW: There is considerable interest in glutamine and selenium in
      critical care as both offer the potential to enhance host defences, through
      different but complimentary mechanisms and may reduce subsequent infections and
      mortality. The SIGNET trial (randomized controlled factorial trial) is the
      largest, critical care study of both supplements. The data have been presented
      publicly, but the data are not published or available for review and will
      therefore not be discussed fully in this update. In the present review I will
      explore the recently available (past 1-2 years) published literature. RECENT
      FINDINGS: The current literature demonstrates that there are currently
      insufficient data to enable confident recommendations on the optimal route,
      timing, duration and dosage of each of these nutritional supplements. The pending
      results of SIGNET, the largest critical care trial of parenteral nutrition
      supplemented by glutamine and or selenium promises to clarify some of the current
      ambiguities and inform future practice. SUMMARY: To be able to confidently
      establish or refute the hypothesis that either glutamine or selenium alone or in
      combination improves outcome in critical care requires a well designed
      prospective randomized controlled trial. To design such a trial we require the
      optimal dose and duration of the nutritional supplement (balancing efficacy and
      toxicity, ease of administration and cost) and then conduct an adequately powered
      trial. Such a trial is still lacking for these two agents. There are some
      supportive data for selenium but the case is less strong for parenteral glutamine
      and weakest for enteral glutamine.

PMID- 20040861
TI  - Metabolic support of the obese intensive care unit patient: a current
      perspective.
AB  - PURPOSE OF REVIEW: Obesity is a widespread condition associated with a variety of
      mechanical, metabolic, and physiologic changes that affect both health outcomes
      and delivery of care. Nutrition support is a key element of management during
      critical illness known to improve outcomes favorably, but is likewise complicated
      in the presence of obesity. This review serves to discuss the challenges unique
      to management of critically ill obese patients and an evidence-based approach to
      nutrition support in this patient population. RECENT FINDINGS: High-protein,
      hypocaloric feeding has emerged as a nutrition support strategy capable of
      reducing hyperglycemia and protein catabolism, while promoting favorable changes
      in body composition and fluid mobilization. Recent data have shown a protective
      effect of mild-moderate obesity (BMI 30-39.9 kg/m2), with improved morbidity and
      mortality outcomes in this subgroup. Therefore, it is unclear whether hypocaloric
      feeding represents an inferior approach in this subgroup in which weight
      maintenance may be preferable. SUMMARY: There are many obstacles that limit
      provision of nutrition support in the obese ICU patient. Calculating energy needs
      accurately is extremely problematic due to a lack of reliable prediction
      equations and a wide variability in body composition among the obese patients.
      Further research is needed to determine a better approach to estimating energy
      needs in this population, in addition to validating hypocaloric feeding as the
      standard approach to nutrition support in the obese patients.

PMID- 20040862
TI  - Comparisons of different insulin infusion protocols: a review of recent
      literature.
AB  - PURPOSE OF REVIEW: To provide an update on the currently available insulin
      infusion protocols for treatment of hyperglycemia in critically ill patients and
      to discuss the major differences and similarities among them. RECENT FINDINGS: We
      identified a total of 26 protocols, 20 of which used manual blood-glucose
      calculations, and six that used computerized algorithms. The major differences
      and similarities among the insulin infusion protocols were in the following
      areas: patient characteristics, target glucose level, time to achieve target
      glucose level, incidence of hypoglycemia, rationale for adjusting the rates of
      insulin infusion, and methods of blood-glucose measurements. Several computerized
      protocols hold promise for safer achievement of glycemic targets. SUMMARY:
      Insulin infusion is the most effective method for controlling hyperglycemia in
      critically ill patients. Clinicians should utilize a validated insulin infusion
      protocol that is well tolerated, and is most appropriate and practical for their
      institution based on the resources that are available.

PMID- 20040863
TI  - STAT3 and its activators in intestinal defense and mucosal homeostasis.
AB  - PURPOSE OF REVIEW: Coordination of innate and adaptive immunity is central to
      effective mucosal immune defense and homeostasis. The review discusses recent
      findings on two cytokines, IL-22 and IL-6, and their common signaling pathway,
      which bridge innate and adaptive immunity in the intestinal tract. RECENT
      FINDINGS: IL-22, a signature product of Th17 cells, is also secreted at
      functionally significant levels by innate immune cells, especially NKp44/NKp46
      expressing natural killer (NK) cells and lymphoid tissue inducer cells after IL
      23 stimulation. IL-22 acts primarily on epithelial cells and is overall
      protective, as its inhibition or loss exacerbates intestinal inflammation.
      Similarly, IL-6, secreted by macrophages, dendritic cells, epithelial cells, and
      T cells protects against mucosal damage, but it is also key in the development of
      Th17 cells, which mediate inflammatory and defensive responses in the intestine.
      Both cytokines activate STAT3 signaling, whose intestinal activities depend on
      the specific cell types involved. STAT3 in epithelial and myeloid cells mediates
      mucosa-protective and anti-inflammatory functions, whereas STAT3 in T cells
      promotes inflammation. SUMMARY: IL-22 and IL-6 are prime examples of cytokines
      that coordinate innate and adaptive immune responses in the intestine. They and
      their common signaling pathway, STAT3 can promote or protect against inflammation
      indicating that pharmacological manipulation for therapeutic purposes in
      intestinal inflammatory conditions may present special challenges.

PMID- 20040864
TI  - Celiac disease.
AB  - PURPOSE OF REVIEW: To summarize recent advances in celiac disease published
      between August 2008 and July 2009. RECENT FINDINGS: Celiac disease affects nearly
      1% of most populations but remains largely unrecognized. In the last year, work
      has shown that the prevalence of celiac disease has increased dramatically, not
      simply due to increased detection. Also, undiagnosed celiac disease may be
      associated with increased mortality. Significant progress has been made in
      understanding how gliadin peptides can cross the intestinal border and access the
      immune system. New genetic loci and candidate genes that may contribute to the
      risk of celiac disease and its overlap with type 1 diabetes mellitus have been
      identified. Novel deamidated gliadin peptides antibodies have better diagnostic
      accuracy over native gliadin-based tests. The inclusion of duodenal bulb biopsy
      specimens may increase the rate of celiac disease detection. The spectrum of
      celiac disease likely includes a minority of patients with mild enteropathy. A
      practical seven-item instrument may facilitate standardized evaluation of gluten
      free diet adherence. Finally, refractory celiac disease, although rare, is
      associated with a poor prognosis. SUMMARY: Celiac disease is a global health
      problem that requires a multidisciplinary and increasingly cooperative
      multinational research effort.

PMID- 20040866
TI  - T lymphocytes: a role in hypertension?
AB  - PURPOSE OF REVIEW: Low-grade inflammation has been shown to play a role in
      cardiovascular disease and specifically in hypertension. Circulating and tissue
      leukocytes and macrophages are a component of the mechanisms leading to
      inflammatory responses. Subsets of T lymphocytes have been implicated in the
      pathogenesis of hypertension and vascular remodeling. This is an area of active
      research and rapid development in cardiovascular and renal disease which offers
      great therapeutic potential. RECENT FINDINGS: Recent data suggest that subsets of
      T lymphocytes, both effector T cells such as T-helper (Th)1 (interferon-gamma
      producing) and Th2 lymphocytes [that produce interleukin (IL)-4], as well as Th17
      (that produce IL-17), and T suppressor lymphocytes including regulatory T cells
      (Treg), which express the transcription factor forkhead box P3 (Foxp3), play
      critical roles in the development of angiotensin II, deoxycorticosterone salt
      sensitive and Dahl salt-sensitive hypertension, and in the progression of
      vascular remodeling. As well, recent evidence suggests that the inflammatory
      response involving T lymphocytes may be triggered by oxidative stress in nuclei
      of the brain and associate with blood pressure elevation. SUMMARY: These new data
      implicating T lymphocytes will eventually allow discovery of new therapeutic
      targets that may improve outcomes in cardiovascular and renal disease in humans.

PMID- 20040867
TI  - Diagnosing chronic kidney disease.
AB  - PURPOSE OF REVIEW: To review the current state-of-the art in diagnosing chronic
      kidney disease (CKD) using classification systems based on estimated glomerular
      filtration rate (eGFR) and kidney damage. RECENT FINDINGS: CKD, as defined by
      current classification systems, has many pitfalls, but the presence and stage of
      CKD has important value in determining prognosis, particularly when the effects
      of albuminuria are added to eGFR SUMMARY: The diagnosis of CKD using current
      classification schema based on eGFR alone needs to be approached with some
      caution, particularly in the elderly without concomitant signs of kidney damage.
      The presence and magnitude of albuminuria has important diagnostic and prognostic
      significance.

PMID- 20040865
TI  - Microbial influences on the small intestinal response to radiation injury.
AB  - PURPOSE OF REVIEW: Injury to the small bowel from ionizing radiation occurs
      commonly in patients undergoing cancer therapy and less commonly in instances of
      accidental radiation overexposure. Several lines of evidence now suggest that
      dynamic interactions between the host's enteric microbiota and innate immune
      system are important in modulating the intestinal response to radiation. Here, we
      will review recent developments in the area of acute radiation enteropathy and
      examine the current state of knowledge regarding the impact of host-microbial
      interactions in the process. RECENT FINDINGS: There is promise in the development
      and testing of new clinical biomarkers including serum citrulline. Toll-like
      receptor agonists and innate immune system signaling pathways including nuclear
      factor-kappa B profoundly alter intestinal epithelial cell apoptosis and crypt
      survival after radiation exposure. Germ-free conditions, probiotics and
      antibiotics are each identified as modifiers of disease development and course. A
      human study suggested that luminal microbiota composition may influence the
      host's intestinal response to radiation and may change in those developing
      postradiation diarrhea. SUMMARY: New knowledge implies that investigations aimed
      at deciphering the microbiome-host interactions before and after small bowl
      radiation injury may eventually allow prediction of disease course and offer
      opportunities for the development of novel therapeutic or prophylactic
      strategies.

PMID- 20040868
TI  - Arterial aging: a journey into subclinical arterial disease.
AB  - PURPOSE OF REVIEW: Age-associated arterial alterations in cells, matrix, and
      biomolecules are the foundation for the initiation and progression of
      cardiovascular diseases in older persons. This review focuses on the latest
      advances on the intertwining of aging and disease within the arterial wall at the
      cell and molecular levels. RECENT FINDINGS: Endothelial dysfunction, vascular
      smooth muscle cell (VSMC) proliferation/invasion/secretion, matrix fragmentation,
      collagenization and glycation are characteristics of an age-associated arterial
      phenotype that creates a microenvironment enriched with reactive oxygen species
      (ROS) for the pathogenesis of arterial disease. This niche creates an age
      associated arterial secretory phenotype (AAASP), which is orchestrated by the
      concerted effects of numerous age-modified angiotensin II signaling molecules.
      Most of these biomolecular, cell, and matrix modifications that constitute the
      AAASP can be elicited by experimental hypertension or atherosclerosis at a
      younger age. The arterial AAASP also shares features of a senescence-associated
      secretory phenotype (SASP) identified in other mesenchymocytes, that is,
      fibroblasts. SUMMARY: A subclinical AAASP evolves during aging. Targeting this
      subclinical AAASP may reduce the incidence and progression of the quintessential
      age-associated arterial diseases, that is, hypertension and atherosclerosis.

PMID- 20040869
TI  - Long-term outcomes of kidney donors.
AB  - PURPOSE OF REVIEW: Partial renal ablation in laboratory animals leads initially
      to compensatory glomerular hyperfiltration and progressive, sclerotic kidney
      disease. In addition, modest declines in kidney function are associated with
      premature mortality in epidemiological studies. Hence, the long-term safety of
      living-kidney donation is an important issue. The purpose of this review was to
      examine existing research on outcomes among living-kidney transplant donors, with
      a focus on longer term outcomes. RECENT FINDINGS: Although studies with sibling
      controls are unavailable, the current evidence base suggests that kidney donors
      have mortality and end-stage renal disease risks that are equivalent to similar
      individuals in the general population. Although findings for albuminuria and
      hypertension vary between studies, risks may be acceptable if donors receive
      optimal follow-up and care. Parenthetically, viewed as an experimental model of
      kidney-function loss, the neutrality of outcomes among donors may have major
      implications for the population at large: the robust associations between modest
      declines in kidney function and mortality seen in the general population suggest
      a confounded relationship and finding these confounders could have major
      implications for future research directions and for public health. SUMMARY: Long
      term outcomes suggest that kidney donation is not a major threat to longevity.

PMID- 20040870
TI  - Role of extracellular matrix in vascular remodeling of hypertension.
AB  - PURPOSE OF REVIEW: Arterial stiffness due to alterations in extracellular matrix
      is one of the mechanisms responsible for increased peripheral resistance in
      hypertension. Recent evidence points to arterial stiffness as an independent
      predictor of cardiovascular events. This review focuses on recent advances in the
      biology of extracellular matrix proteins involved in hypertension-associated
      vascular changes. RECENT FINDINGS: The vascular extracellular matrix is a complex
      heterogeneous tissue comprising collagens, elastin, glycoproteins, and
      proteoglycans. These constituents not only provide mechanical integrity to the
      vessel wall but also possess a repertoire of insoluble ligands that induce cell
      signaling to control proliferation, migration, differentiation, and survival. It
      is now evident that it is not only the quantity but also the quality of the new
      synthesized extracellular matrix that determines changes in vascular stiffness in
      hypertension. Also, the control of cross-linking and the interactions between the
      extracellular matrix and vascular cells seem to be important. SUMMARY: It is now
      evident that some of the currently used antihypertensive therapies can correct
      vascular stiffness and fibrosis. A better understanding of molecular mechanisms
      underlying alterations in extracellular matrix in hypertension will provide
      insights into novel therapies to reduce arterial stiffness and will identify new
      roles of established antihypertensive drugs.

PMID- 20040871
TI  - Descemet's stripping with automated endothelial keratoplasty and glaucoma.
AB  - PURPOSE OF REVIEW: Descemet's stripping with automated endothelial keratoplasty
      (DSAEK) has recently become the preferred surgical procedure replacing
      penetrating keratoplasty (PKP) for corneal endothelial disorders. However, DSAEK
      may also be associated with postprocedure intraocular pressure elevation and
      secondary glaucoma, and presents unique surgical challenges in patients with
      preexisting glaucoma surgeries. RECENT FINDINGS: The relatively high rate of
      glaucoma induction or worsening after PKP has significant implications leading to
      corneal graft failure and irreversible vision loss from glaucomatous optic
      neuropathy. In contrast, DSAEK, in addition to providing excellent visual
      outcomes with faster recovery, may provide advantages over PKP with lower risk of
      serious, vision-threatening glaucoma-related complications. Pupillary block
      glaucoma, steroid-induced intraocular pressure elevation, and less commonly
      peripheral anterior synechiae development have been reported after DSAEK. In
      patients with preexisting glaucoma surgical procedures (trabeculectomy or tube
      shunts), special attention to techniques (which continue to evolve) are required
      to perform DSAEK safely and effectively. SUMMARY: As DSAEK continues to gain
      popularity and advance with more studies performed, our understanding of DSAEK
      associated intraocular pressure elevation and secondary glaucoma-related
      complications will become more complete. Current limited data suggest that DSAEK
      may be a suitable surgical alternative to PKP in patients with corneal
      endothelial disease and coexistent glaucoma with or without prior glaucoma
      procedures with faster recovery and good visual outcomes.

PMID- 20040873
TI  - Glaucoma in Latinos/Hispanics.
AB  - PURPOSE OF REVIEW: Large differences exist in the prevalence of glaucoma among
      different racial and ethnic groups. The purpose of this article is to review the
      findings of the Los Angeles Latino Eye Study (LALES) with respect to the
      prevalence of glaucoma in Latinos and to identify factors associated with the
      development of glaucoma in this population. RECENT FINDINGS: LALES is the largest
      prevalence survey of eye disease in Latinos of Mexican origin to date. This
      review discusses the findings of LALES, including data that demonstrate specific
      risk factors and manifestations of open-angle glaucoma in this rapidly growing
      population. SUMMARY: The LALES data on ocular disease among Latinos of Mexican
      ancestry have crucial implications for effective clinical and public-health
      interventions. Understanding the particular characteristics of glaucoma in the
      Latino population is essential for correct diagnosis and management of this
      potentially blinding condition.

PMID- 20040872
TI  - Review of results from the Tube Versus Trabeculectomy Study.
AB  - PURPOSE OF REVIEW: 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
      unsuccessful glaucoma surgery. This article reviews published results from the
      TVT Study. RECENT FINDINGS: Tube-shunt surgery had a higher success rate than
      trabeculectomy with MMC during the first 3 years of follow-up. Trabeculectomy
      with MMC produced greater intraocular pressure (IOP) reduction in the early
      postoperative period compared with tube-shunt placement, but similar IOPs were
      observed after 3 months. Tube-shunt surgery was associated with greater use of
      adjunctive-medical therapy than trabeculectomy with MMC during the first 2 years
      of the study, but no difference in medication use was seen at 3 years. The
      incidence of postoperative complications was higher after trabeculectomy with MMC
      compared with tube-shunt surgery, but serious complications associated with
      vision loss and/or reoperation developed with similar frequency after both
      surgical procedures. No difference in the rate of vision loss was present
      following trabeculectomy with MMC and tube-shunt surgery after 3 years of follow
      up. Cataract progression was common, but occurred with similar frequency with
      both procedures. SUMMARY: Intermediate-term results of the TVT Study support the
      expanded use of tube shunts beyond refractory glaucomas. Tube-shunt surgery is an
      appropriate surgical option in patients who have undergone prior cataract and/or
      unsuccessful filtering surgery.

PMID- 20040874
TI  - The effect of cataract extraction on intraocular pressure.
AB  - PURPOSE OF REVIEW: To review the current ophthalmic literature regarding the
      impact of modern cataract surgery on intraocular pressure (IOP). RECENT FINDINGS:
      Many articles in the literature demonstrate a modest, long-lasting decrease in
      IOP following phacoemulsification and posterior chamber intraocular lens
      implantation in patients with primary open-angle glaucoma and ocular
      hypertension. The mechanism of this average pressure-lowering effect has yet to
      be elucidated. The IOP reductions obtained in patients with angle closure
      glaucoma are often more pronounced than those seen in patients with open angles.
      Patients with higher levels of preoperative IOP obtain greater average reductions
      in IOP, although this phenomenon may partially be explained by a statistical
      effect known as regression to the mean. SUMMARY: Although it is well recognized
      that phacoemulsification may result in a modest sustained reduction in IOP, there
      are several limitations in the studies that have assessed the magnitude of this
      effect. The implications of such IOP reduction with cataract surgery on the
      medical and surgical algorithms for care in patients with open-angle glaucoma and
      coexistent cataract remain unclear. In contrast, the substantial benefits of
      cataract surgery in patients with acute and chronic angle-closure glaucoma have
      been well studied and are generally widely accepted. An improved understanding of
      the pathophysiological mechanisms of IOP lowering after cataract extraction may
      help us better predict which patients are most likely to benefit from simple
      cataract extraction, obviating the need for combined cataract and glaucoma
      surgical procedures in such circumstances.

PMID- 20040875
TI  - Anti-VEGF therapy for glaucoma.
AB  - PURPOSE OF REVIEW: The role of antivascular endothelial growth factor (anti-VEGF)
      agents in treating various ophthalmic diseases is currently being investigated.
      There have been many advances in the understanding of how anti-VEGF agents work
      and speculation on when to implement them clinically for neovascular glaucoma.
      Recent studies exploring the utility of anti-VEGF agents for wound modulation
      after trabeculectomy reveal promising results. RECENT FINDINGS: Anti-VEGF agents
      have been shown to be beneficial in treating neovascular glaucoma. Their use
      leads to regression of both iris and angle neovascularization, intraocular
      pressure control when the angle remains open and, in many cases, prompts
      symptomatic improvement. In addition, research on the wound modulatory properties
      of anti-VEGF agents has revealed a dose-dependent inhibition of fibroblast
      proliferation. Studies exploring the use of anti-VEGF agents at time of
      trabeculectomy or in bleb revision procedures suggest a beneficial effect on bleb
      survival and subsequent improvement in intraocular pressure control. Prospective
      randomized clinical trials are still needed. SUMMARY: The recent use of anti-VEGF
      agents for neovascular glaucoma as well as wound modulation after trabeculectomy
      has shown great promise. Through future research, the antiangiogenic and
      antifibroblastic properties of anti-VEGF agents may prove to be beneficial in
      patients being treated for various forms of glaucoma.

PMID- 20040876
TI  - Intracranial pressure and glaucoma.
AB  - PURPOSE OF REVIEW: Glaucoma remains a disease with an unclear basic
      pathophysiology. The optic nerve travels through two pressurized regions: the
      intraocular space and the intracranial space. Some authors have suggested that
      the relationship between intraocular pressure and intracranial pressure may play
      a fundamental role in the development of glaucoma. RECENT FINDINGS: Recent
      studies have shown that intracranial pressure is lower in patients with glaucoma
      and normal-tension glaucoma. Conversely, intracranial pressure appears to be
      elevated in patients with ocular hypertension. Early mathematical modeling
      studies have suggested that the counterbalance provided by intracranial pressure
      would be an important factor in the development of glaucoma. SUMMARY: The
      relationship between intraocular pressure and intracranial pressure may play an
      important role in the development of glaucoma.

PMID- 20040877
TI  - Intraocular lens choices for patients with glaucoma.
AB  - PURPOSE OF REVIEW: To discuss the unique functional and structural changes in
      glaucoma and the impact on intraocular lens (IOL) selection. RECENT FINDINGS:
      Glaucoma is a common ocular disease. Functional and structural changes associated
      with glaucoma require special consideration in the patient who is undergoing
      cataract/IOL surgery. Decreased contrast sensitivity found in glaucoma may be
      enhanced by the use of aspheric IOLs. Small pupils and weakened zonules
      necessitate meticulous surgical technique and increase the risk of IOL
      dislocation, as does anterior capsular contraction. Posterior capsular
      opacification is a common postoperative complication and may be related to IOL
      material and design. Both anterior chamber depth and axial length may change in
      patients who have had trabeculectomy and should be considered in the preoperative
      plan. Multifocal IOLs may afford spectacle independence for patients; however,
      there is a paucity of data for their use in concurrent ocular disease. SUMMARY:
      Although there are challenges in performing cataract surgery in patients with
      glaucoma, excellent outcomes may be obtained with proper preoperative planning,
      meticulous intraoperative technique, and appropriate selection of IOL design.

PMID- 20040878
TI  - Under-treatment of cancer pain.
AB  - PURPOSE OF REVIEW: Cancer pain remains inadequately treated, despite
      internationally accepted management guidelines and a myriad of treatment options.
      Risk factors for undertreatment are reviewed, along with possible explanations.
      Recent studies documenting the scope of the problem as well as investigating
      solutions are discussed with clinical-practice recommendations outlined. RECENT
      FINDINGS: Women over 65 years of age representative of a cultural minority, with
      earlier stage disease, cared for at home, and with high-school education or less
      are at highest risk of having uncontrolled cancer pain. Optimal treatment is
      impeded by patients' maladaptive beliefs, nonadherence, underreporting or
      miscommunication with caregivers; from a healthcare provider perspective, it may
      be due to inadequate assessment, documentation, knowledge, and communication.
      Emerging data support the vital influence of lay caregivers on appropriate pain
      management. Although home-education programs may decrease pain and improve
      quality of life, there are also less intensive approaches deliverable by
      individuals to holistically address pain. SUMMARY: Prospective study of barriers
      to both delivery and receipt of adequate pain management is needed, as the
      majority of published literature is based on survey studies. Treatment must be
      individualized based on clinical circumstances and patient wishes, with the goal
      of maximizing function and quality of life.

PMID- 20040879
TI  - Regimen-related gastrointestinal toxicities in cancer patients.
AB  - PURPOSE OF REVIEW: Gastrointestinal toxicities are a common side effect of many
      forms of cytotoxic cancer therapy. Of the gastrointestinal toxicities, mucositis
      is among the most common and results in a range of symptoms that negatively
      impact patients' quality of life, ability to tolerate their cancer therapy, and
      health resource use. The purpose of this review is to describe the scope, risk
      factors, pathobiology, and treatment opportunities for mucositis. RECENT
      FINDINGS: The historical paradigm by which mucositis occurs has been markedly
      revised in the past decade. The pathogenesis of mucositis is now recognized to
      consist of a series of complex biological events that ultimately result in the
      disruption of the integrity of the gastrointestinal tract. Risk factors for
      mucositis have been identified that are associated with its biology. Treatment
      strategies that target mucositis' mechanistic pathways hold significant promise.
      SUMMARY: Mucosal injury induced by radiation or chemotherapy is a common,
      painful, function disrupting toxicity that, currently, has limited treatment
      options. The evolving understanding of the pathobiology of the condition provides
      multiple treatment targets that should ultimately result in amelioration of the
      condition.

PMID- 20040880
TI  - High-intensity aerobic exercise training improves the heart in health and
      disease.
AB  - Regular exercise training confers beneficial effects to the heart as well as to
      the entire body. This occurs partly because exercise training improves skeletal
      muscle work capacity and reduces resistance, thus increasing conductance in the
      peripheral circulation. More directly, exercise training also alters extrinsic
      modulation of the heart and improves the intrinsic pump capacity of the heart.
      Together, these effects allow for improved exercise capacity. Accumulating
      evidence suggests that the magnitude of these benefits increases proportionally
      with the intensity of individual exercise training sessions constituting the
      exercise training program. It has emerged that regular exercise training also
      confers beneficial effects to patients at risk for, or who have, established
      heart dysfunction and disease and, moreover, that exercise training may reduce
      the dysfunction of the heart itself and, at least, partly restore its ability to
      effectively function as a pump. The most recent studies in patients with
      established heart disease suggest that a high relative, yet aerobic, intensity of
      the exercise training improves the intrinsic pump capacity of the myocardium, an
      effect not previously believed to occur with exercise training. However, more and
      larger studies are needed to establish the safety and efficacy of such exercise
      training in patients with heart disease. Here, we consider the nature of the
      intensity dependence of exercise training and the causes of the improved heart
      function.

PMID- 20040881
TI  - Interstitial lung disease and pulmonary rehabilitation.
AB  - Interstitial lung disease (ILD) is a heterogeneous group of lung disorders
      associated with exertional dyspnea, hypoxemia, which is often worse with
      activity, and deconditioning. The majority of evidence supporting the
      effectiveness of pulmonary rehabilitation (PR) comes from studies of persons with
      obstructive disorders such as chronic obstructive pulmonary disease. However,
      growing evidence supports the use of PR as an effective and safe intervention for
      persons with ILD. Despite the lack of clinical guidelines for PR in ILD, several
      recent studies have shown effectiveness of PR in improvement of dyspnea and
      function in patients with ILD. This article reviews the current evidence for PR
      in ILD and suggests an approach to management.

PMID- 20040882
TI  - Cardiovascular rehabilitation in patients with diabetes.
AB  - PURPOSE: The cardiovascular disease risk profile and exercise capacity of
      coronary heart disease patients with type 2 diabetes mellitus (DM) were measured
      and compared with those of nondiabetic (NDM) patients before and after a 6-week
      multidisciplinary cardiac rehabilitation program. METHODS: Subjects included 413
      patients with DM (56.9 +/- 7.9 years) and 614 patients with NDM (56.8 +/- 10.3
      years). RESULTS: At program entry, DM patients had a higher prevalence of risk
      factors (hypertension, hypercholesterolemia, hypertriglyceridemia, obesity,
      excess abdominal fat, and depression), had a lower peak oxygen uptake (14.3 +/-
      4.4 vs 16.6 +/- 5.4 mL . kg . min; P < .001), and covered a shorter distance in
      the 6-minute walk test (404 +/- 117 m vs 445 +/- 116 m; P < .001) than NDM
      patients. At the end of the exercise program, all patients achieved significant
      improvements in physical capacity, which were similar in DM and NDM patients
      (+27.6 +/- 28.2% vs +30.5 +/- 27.7% for peak oxygen uptake and +21.0 +/- 31.5% vs
      +21.3 +/- 53.2% for the 6-minute distance test). CONCLUSION: DM patients with
      coronary heart disease had a higher prevalence of cardiovascular disease risk
      factors as well as lower physical capacity than NDM patients at the beginning of
      rehabilitation. All patients demonstrated improvement in exercise capacity after
      rehabilitation. More importantly, the extent of the improvement was similar in DM
      and NDM patients. This study, which involved a large population, emphasizes the
      capacity of DM patients to fully benefit from a multidisciplinary risk factor
      management program, including exercise training and educational programs.

PMID- 20040883
TI  - Six-minute walk distance in patients with severe end-stage COPD: association with
      survival after inpatient pulmonary rehabilitation.
AB  - PURPOSE: To evaluate the relationship between the 6-minute walk distance (6MWD)
      and survival in a cohort of patients with severe end-stage chronic obstructive
      pulmonary disease (COPD) who received inpatient pulmonary rehabilitation (IPR)
      from 1995 to 2007. METHODS: We retrospectively analyzed 815 patients with severe
      end-stage COPD who received IPR. 6MWDs before and after IPR (pre-6MWD, post-6MWD)
      were compared to assess whether 6MWD was significantly changed after IPR. The
      Kaplan-Meier survival curves were constructed to show the relationship between
      survival and 6MWD. The age- and or comorbidities-adjusted Cox proportional hazard
      model was applied to assess association between the survival and the pre-6MWD,
      post-6MWD, or difference in 6MWD from the pre-6MWD to post-6MWD (Delta6MWD).
      RESULTS: Baseline demographics demonstrated a median age 74.0 years, mostly women
      (60.1%), and white (89.9%) patients with significant comorbid diseases who were
      most recently hospitalized in acute care facilities (95.1%). IPR significantly
      increased the 6MWD (mean distance change: 86.4 m; 95% confidence interval [CI],
      81.5-91.3 m). Pre-6MWD was not significantly associated with survival. However,
      post-6MWD was significantly associated with age- and comorbidity-adjusted
      survival (post-6MWD hazard ratio = 1.336; 95% CI, 1.232-1.449 [post-6MWD x m
      relative to post-6MWD 2x m]), and Delta6MWD was also significantly associated
      with age-, comorbidities-, and pre-6MWD-adjusted survival (Delta6MWD hazard ratio
      = 1.337; 95% CI, 1.227-1.457 [Delta6MWD x m relative to Delta6MWD 2x m]).
      CONCLUSIONS: In patients with severe end-stage COPD, IPR significantly improved
      6MWD, and the post-6MWD and Delta6MWD were positively associated with the length
      of survival.

PMID- 20040884
TI  - Randomized trial assessing the impact of a musculoskeletal intervention for pain
      before participating in a weight management program.
AB  - PURPOSE: Obesity increases the risk of developing physical disability and pain.
      Persons with a body mass index (BMI) of 30 kg/m or more have an increased risk
      for osteoarthritis compared with those with a BMI between 25 and 29 kg/m. The
      purpose of this study was to examine the effect of treatment directed at reducing
      musculoskeletal pain on weight loss in obese subjects prior to participation in a
      6-month weight management (WM) program. METHODS: Subjects (BMI > or = 30 kg/m; n
      = 54, female = 41, male = 13) with musculoskeletal pain, as assessed by a visual
      analog scale score of more than 5, were randomized to a physician musculoskeletal
      evaluation with treatment and physical therapy prior to participation in a 6
      month WM program (intervention) or direct entry into the WM program (control)
      between November 10, 2003, and January 20, 2005. RESULTS: Seventy-six percent of
      subjects completed the study (intervention, n = 18 [67%]; control, n = 23 [85%],
      P = .10). The intervention group demonstrated a significant decrease in visual
      analog scale score after musculoskeletal therapy (2.3 +/- 1.8, P < .0001).
      Despite a reduction in pain levels in the intervention group compared with the
      control group at the start of the WM program, there were no significant
      differences between the groups in percentage weight loss (P = .80), body fat
      composition (P = .20), or BMI (P = .06), all significantly improved in both
      groups. CONCLUSIONS: Musculoskeletal and physical therapy intervention directed
      at decreasing musculoskeletal pain in obese individuals prior to participation in
      a WM program reduces reported musculoskeletal pain for those participants
      completing the program but does not significantly improve weight loss over 6
      months, compared with individuals with comparable musculoskeletal pain who enter
      directly into a WM program.

PMID- 20040885
TI  - Urotensin II activates sarcolemmal Na+/H+ exchanger in adult rat ventricular
      myocytes.
AB  - OBJECTIVES: Our aims in the present study were (1) to determine the effects of
      urotensin II (UT-II) on the sarcolemmal Na/H exchanger (NHE1) activity, and (2)
      to investigate possible kinase pathways for UT-II-mediated NHE1 stimulation.
      METHODS: In single rat ventricular myocytes (n = 5-10/group) loaded with the pH
      sensitive fluoroprobe carboxy-seminaphthorhodafluor-1, acid efflux rates (JH)
      were determined as an index of NHE1 activity by rate of recovery of intracellular
      pH (pHi) from NH4Cl-induced acidosis and the intrinsic buffering power.
      Phosphorylation of extracellular signal-regulated kinase (ERK), a key kinase of
      NHE1 activation, was determined by Western blot analysis. RESULTS: JH increased
      by 31%-71% relative to control in the presence of 100 nmol/L UT-II at pHi range
      of 6.6-7.0. Stimulation of NHE1 activity by UT-II was abolished by inhibitors of
      phospholipase C, protein kinase C, and ERK kinase; 2-nitro-4-carboxyphenil-N,N
      diphenilcarbamate at 100 micromol/L, GF109203X at 300 nmol/L, and PD98059 at 50
      micromol/L, respectively. Moreover, UT-II at 100 nmol/L produced a significant
      increase in cellular ERK1/2 phosphorylation, which was also inhibited by those
      inhibitors. CONCLUSIONS: Our study was the first to demonstrate that UT-II
      activates the cardiac sarcolemmal NHE1 and that the phenomenon may involve, at
      least in part, the phospholipase C-protein kinase C-ERK pathway.

PMID- 20040886
TI  - Microvascular effects of centrally acting antihypertensive drugs in spontaneously
      hypertensive rats.
AB  - We investigated the effects of oral long-term antihypertensive treatment using
      centrally acting sympathoinhibitory drugs on capillary density in the skin,
      skeletal muscle, and heart in the spontaneously hypertensive rat (SHR). Wistar
      Kyoto rats (WKY) were used as normotensive control groups. Functional capillary
      density was assessed using intravital fluorescence videomicroscopy and structural
      capillary density with histochemical analysis. Groups of 10 SHRs were orally
      treated over 28 days with clonidine (0.1 mg x kg x d), rilmenidine (1 mg x kg x
      d), or moxonidine (10 mg x kg x d). A group of WKY was also treated with
      clonidine (0.1 mg x kg x d). Treatment with all antihypertensive drugs induced a
      normalization of arterial pressure accompanied by a reversion of functional
      capillary rarefaction in the skeletal muscle and skin of SHR. Clonidine treatment
      also reduced arterial pressure and increased functional capillary density in the
      skin and skeletal muscle of WKY. Histochemical analysis showed that SHR had a
      lower capillary to fiber ratio in the skeletal muscle (P < 0.0001), which was
      normalized by all treatments. The capillary volume density to fiber volume
      density ratio in the left ventricle of SHR was also significantly reduced (P <
      0.0001). However, myocardial capillary rarefaction was not altered by the
      different treatments. In conclusion, the results showed that long-term
      antihypertensive treatment with centrally acting drugs enhanced tissue perfusion
      and reversed capillary rarefaction in the skeletal muscle of SHRs.

PMID- 20040887
TI  - Inhibition of matrix deposition: a new strategy for prevention of restenosis
      after balloon angioplasty.
AB  - Restenosis after balloon angioplasty or stent placement is characterized by local
      accumulation of mainly vascular smooth muscle cells and the synthesis of
      extracellular matrix molecules (ECM).We hypothesized that inhibition of ECM
      synthesis represents a strategy to prevent trauma-induced neointima formation.
      Rats were treated with pirfenidone (1 g/kg of body weight orally.), an inhibitor
      of growth factor-induced collagen synthesis, and subjected to balloon denudation
      of the carotid artery. Two weeks later, computer-aided morphometry was done and
      compared with untreated controls (each n = 6). Neointimal proliferative activity
      was quantified immunohistochemically by counting PCNA-positive nuclei, and
      collagen deposition was visualized by picrosirius red staining and semi
      quantified by Northern blot. Control-injured animals developed marked neointimal
      thickening within 2 weeks (I/M, mean intima to media ratio: 2.42 +/- 0.15)
      resulting in an 89.2% luminal narrowing. The neointima mainly consisted of
      vascular smooth muscle cells embedded in collagen. Neointima formation was
      strongly reduced when balloon-injured animals had been treated with pirfenidone
      (I/M ratio 0.22 +/- 0.08, P < 0.001), resulting in a minimal residual narrowing
      of the lumen (7.9%). I/M ratio did not further increase even after
      discontinuation of the drug for 14 days (0.35 +/- 0.13). Proliferative activity
      within the neointima was unaffected by the drug, 4.4% versus 4.8% of neointimal
      cells stained positive for PCNA in carotid arteries of treated versus untreated
      animals, respectively. However, picrosirius red staining demonstrated marked
      attenuation of collagen deposition, a finding that was further confirmed by
      Northern blot of homogenized vessels. Pirfenidone, currently being investigated
      clinically for the treatment of various fibrotic diseases, is able to prevent
      neointimal lesion formation most likely through inhibition of local ECM
      deposition. Targeting matrix deposition may have an intriguing potential for the
      prevention of vascular proliferative diseases.

PMID- 20040888
TI  - Sympathoinhibition induced by centrally administered atorvastatin is associated
      with alteration of NAD(P)H and Mn superoxide dismutase activity in rostral
      ventrolateral medulla of stroke-prone spontaneously hypertensive rats.
AB  - Oxidative stress in the rostral ventrolateral medulla (RVLM) increases
      sympathetic nervous system activity (SNA). Oral treatment with atorvastatin
      decreases SNA through antioxidant effects in the RVLM of stroke-prone
      spontaneously hypertensive rats (SHRSP). We aimed to examine whether centrally
      administered atorvastain reduces SNA in SHRSP and, if so, to determine whether it
      is associated with the reduction of oxidative stress induced by alteration of
      activities of nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase and
      superoxide dismutase (SOD) in the RVLM of SHRSP. SHRSP received atorvastatin (S
      ATOR) or vehicle (S-VEH) by continuous intracerebroventricular infusion for 14
      days. Mean blood pressure, heart rate, and SNA were significantly lower in S-ATOR
      than in S-VEH. Oxidative stress, Rac1 activity, NAD(P)H oxidase activity, Rac1,
      gp91(phox) and p22(phox) expression in the membrane fraction, and p47(phox) and
      p40(phox) expression in the cytosolic fraction in the RVLM were significantly
      lower in S-ATOR than in S-VEH. Rac1 expression in the cytosolic fraction and Mn
      SOD activity, however, were significantly higher in S-ATOR than in S-VEH. Our
      findings suggest that centrally administered atorvastatin decreases SNA and is
      associated with decreasing NAD(P)H oxidase activity and upregulation of Mn-SOD
      activity in the RVLM of SHRSP, leading to suppressing oxidative stress.

PMID- 20040889
TI  - Ephedrine controls heart rhythms by activating cardiac I(ks) currents.
AB  - Ephedrine (Eph) is an alkaloid extracted from the Chinese traditional medicine
      plant Ephedra Sinica or Ma huang, which has been known for effects on the central
      nervous system, cardiovascular system, and smooth muscles. However, the
      corresponding molecular mechanism of these effects remains unknown. In this
      study, we investigated the influences of Eph on heart rate, QTc interval in vivo,
      and the slowly activated K channels (IKs) that were composed of both KCNQ1 and
      KCNE1 subunits in vitro. Results demonstrated that Eph, but not pseudoephedrine,
      could increase the heart rate and shorten QTc interval of BALB/c mouse. Besides,
      Eph markedly activated cardiac IKs currents with EC50 = 50 nM and shifted G-V
      curves to left. But pseudoephedrine had no effects on Iks currents. The onset and
      offset time constants of IKs currents activated by Eph at 1 M were tauon = 49
      seconds and tauoff = 400 seconds. A pair of binding sites of Eph on KCNQ1/KCNE1
      channel was also shown to occur at F296 and Y299 in the S5-S6 P-loop of the KCNQ1
      channel. As both amino acids are highly conserved in the KCNQ family, Eph can
      possibly activate other members of the KCNQ family. The mechanism of Iks
      activated by Eph may provide a clue for drug design in the future.

PMID- 20040890
TI  - A population-based study of reduced sleep duration and hypertension: the
      strongest association may be in premenopausal women.
AB  - OBJECTIVES: Recent evidence indicates that reduced sleep duration may be
      associated with an increased risk of hypertension with possibly stronger effects
      among women than men. We therefore examined cross-sectional sex-specific
      associations of sleep duration with hypertension in a large population-based
      sample from the Western New York Health Study (1996<2001). METHODS: Participants
      were 3027 white men (43.5%) and women (56.5%) without prevalent cardiovascular
      disease (median age 56 years). Hypertension was defined as blood pressure at
      least 140 or at least 90&mmHg or regular use of antihypertensive medication.
      Multivariate logistic regression analyses were performed to estimate odds ratios
      (ORs) of hypertension comparing less than 6&h of sleep per night versus the
      reference category (&6&h) while accounting for a number of potential confounders.
      RESULTS: In multivariate analyses, less than 6&h of sleep was associated with a
      significant increased risk of hypertension compared to sleeping at least 6&h per
      night, only among women [OR&=&1.66 (1.09 to 2.53)]. No significant association
      was found among men [OR&=&0.93 (0.62 to 1.41)].In subgroup analyses by menopausal
      status, the effect was stronger among premenopausal women [OR&=&3.25 (1.37 to
      7.76)] than among postmenopausal women [OR&=&1.49 (0.92 to 2.41)]. CONCLUSION:
      Reduced sleep duration, by increasing the risk of hypertension, may produce
      detrimental cardiovascular effects among women. The association is independent of
      socioeconomic status, traditional cardiovascular risk factors, and psychiatric
      comorbidities, and is stronger among premenopausal women. Prospective and
      mechanistic evidence is necessary to support causality.

PMID- 20040891
TI  - Relationship between the 20-m multistage shuttle run test and 2 soccer-specific
      field tests for the assessment of aerobic fitness in adult semi-professional
      soccer players.
AB  - The aim of this study was to examine the relationship of 2 different field tests
      for the assessment of aerobic fitness in soccer players with the multistage 20-m
      test used for the evaluation of maximum oxygen uptake. Nineteen semi-professional
      male soccer players (age: 22.8 +/- 2.5 mean +/- SD) performed, under similar
      conditions, 3 field tests in a counterbalanced order 7 days apart. These tests
      were the multistage 20-m shuttle run test (MSRT), the Bangsbo test, and the Hoff
      test. Heart rate was recorded in all tests with telemetry, and the Borg scale was
      introduced at the end of exercise. Finally, 3-minute post-test lactate
      concentration was determined. Performance was 11.2 +/- 0.9 levels in the MSRT,
      1,658.9 +/- 119.9 m in the Bangsbo test, and 1,798.2 +/- 125.9 m in the Hoff
      test. There was a significant correlation between the Hoff test and performance
      in the MSRT (r = 0.49, p < 0.05). The Bangsbo test was not associated with the
      MSRT score (r = 0.26, p > 0.05). The maximum heart rate achieved in the Bangsbo
      test was significantly lower compared with that in the MSRT and Hoff test
      (Bangsbo: 186.6 +/- 9.6, Hoff: 192 +/- 7.6, MSRT: 190.4 +/- 9.3 beats/min, p <
      0.05). No difference was found in post-test lactate concentration among the 3
      tests. In conclusion, the Hoff test can be used for the assessment of endurance
      in adult semi-professional soccer players. Coaches and teams could benefit from
      using the Hoff test that resembles soccer actions for the assessment of players'
      aerobic fitness.

PMID- 20040892
TI  - Strong relationship between heart rate deflection point and ventilatory threshold
      in trained rowers.
AB  - The purpose of this study was to assess the relationship between heart rate
      deflection point (HRDP) and ventilatory threshold (VT) to the physiological and
      performance variables in a relatively large group of trained men rowers. We
      proposed the hypothesis that physiological and performance variables
      corresponding to HRDP are not significantly different from corresponding
      variables at VT, which would justify the use of HRDP as a simple, affordable, and
      noninvasive method of anaerobic threshold assessment in trained rowers. Eighty
      nine trained men rowers (mean +/- SD: age 21.2 +/- 4.1 years; stature 1.89 +/-
      0.06 m; body mass 89.2 +/- 8.4 kg; VO2max [maximum oxygen uptake] 5.39 +/- 0.62
      L/min-1) completed an incremental rowing ergometer exercise test to exhaustion.
      Three independent, experienced observers determined both HRDP and VT. HRDP was
      determined by visual and computer-aided regression analyses and was evident in
      all rowers. The main findings include (a) there is a strong relationship among
      all observed physiological and performance variables corresponding to HR(HRDP)
      and HR(VT) (r = 0.79-0.96; p < 0.001) and (b) power output, oxygen uptake,
      ventilation, tidal volume and breathing rate corresponding to HR(HRDP) and HR(VT)
      were not significantly different (p >= 0.011), whereas HR(HRDP) was slightly but
      significantly higher than HR(VT) (174.5 vs. 172.8 beats.min-1; p = 0.003). The
      standard error of the estimate in predicting the HR(VT) based on HR(HRDP) was 5.1
      beats.min-1. The subsequent data suggest that, in general, trained rowers may be
      able to periodically assess their aerobic endurance and evaluate the effects of
      training programs using the HRDP method.

PMID- 20040893
TI  - Triaxial modulation of the acceleration induced in the lower extremity during
      whole-body vibration training: a pilot study.
AB  - The purpose of the present study was to quantify vibration transmissibility
      through the lower extremity during exercise on a whole-body vibration (WBV)
      platform. Six healthy adults completed 20 trials of 30-second static squat
      exercise at 30 or 40 degrees of knee flexion angle on a WBV platform working at
      combinations of 5 frequencies (VF: 20, 25, 30, 35, 40 Hz) and 2 amplitudes (VA:
      low, 1.5 mm or high, 3 mm). Accelerations induced by the platform were recorded
      simultaneously at the shank and the thigh using triaxial accelerometers
      positioned at the segmental center of mass. Root-mean-square (RMS) acceleration
      amplitude and transmission ratios between the platform and the leg segments were
      calculated and compared between the experimental conditions. An alpha level of
      0.05 was set to establish significance. Shank vertical acceleration was greatest
      at the lower VF (p = 0.028), higher VA (p = 0.028), and deeper squat (p = 0.048).
      Thigh vertical acceleration was not affected by depth of squat (p = 0.25), but it
      was greatest at higher VA (p = 0.046) and lower VF (p = 0.028). Medial-lateral
      shank acceleration was greatest at higher VF and deeper squat (both p = 0.046)
      and at higher VA (p = 0.028). Medial-lateral thigh acceleration was positively
      related to both VF (p = 0.046) and VA (p = 0.028) but was not affected by knee
      angle (p = 0.46). Anterior-posterior shank acceleration was higher at deeper
      squat (p = 0.046) and at lower VF and higher VA (both p = 0.028). Anterior
      posterior thigh acceleration was related positively to the VA (p = 0.028),
      inversely to the VF (p = 0.028), and not dependent on knee angle (p = 0.75).
      Identification of specific vibration parameters and posture, which underpin WBV
      training efficacy, will enable coaches and athletes to design WBV training
      programs to specifically target shank or thigh muscles for enhanced performance.

PMID- 20040894
TI  - Validity of 2 skinfold calipers in estimating percent body fat of college-aged
      men and women.
AB  - There is a need for cost-effective techniques that accurately predict percent
      body fat (%BF) and require little skill to administer. There are 2 commercially
      available skinfold calipers, 1 digital and the other self-administered, that
      claim to accurately predict %BF. The primary purpose of this study was to
      validate these calipers using dual-energy x-ray absorptiometry (DXA) as a
      reference method in a sample of college-aged men and women. A secondary purpose
      of this study was to compare the validity of these calipers to the validity of
      arm-to-arm bioempedance analysis (BIA) (Omron, Shelton, Connecticut, U.S.A.), leg
      to-leg BIA (Tanita, Arlington Heights, Illinois, U.S.A.), and 3-site skinfold
      equations (SUM3) using DXA as a reference method. Fifty college students (25 men
      and 25 women) from a kinesiology department who ranged in fitness levels
      volunteered to have %BF measured by the digital and self-administered skinfold
      calipers, Omron, Tanita, and SUM3. The digital and self-administered skinfold
      calipers had the poorest group predictive accuracy for the men and women (total
      error ranged from 7.9 to 10.9%BF) when compared to the other field methods. The
      digital skinfold caliper had good individual predictive accuracy in the men (95%
      limits of agreement [LOA] = +/- 6.4%BF) and women (95% LOA = +/- 4.9%BF) when
      compared to the other field methods. However, the self-administered skinfold
      caliper had poor individual predictive accuracy for the men (LOA = +/- 8.6%BF)
      and the women (LOA = +/- 7.5%BF) when compared to the other field methods.
      Compared to DXA, Tanita, Omron, and SUM3, we would not recommend using the
      digital or self-administered skinfold calipers for estimating %BF in college-aged
      men and women with similar body composition as the men and women in this study.
      We recommend using the SUM3 to estimate %BF.

PMID- 20040895
TI  - Effects of various sodium bicarbonate loading protocols on the time-dependent
      extracellular buffering profile.
AB  - Although much research has investigated the types of exercise that are enhanced
      with sodium bicarbonate (NaHCO3) ingestion, to date, there has been limited
      research on the dosage and timing of ingestion that optimizes the associated
      ergogenic effects. This study investigated the effects of various NaHCO3 loading
      protocols on the time-dependent blood-buffering profile. Eight male volunteers
      (age, 22.4 +/- 5.7 yr; height, 179.8 +/- 9.6 cm, body mass, 76.3 +/- 14.1 kg)
      completed Part A, measures of alkalosis throughout 120 minutes after ingestion of
      various single NaHCO3 dosages (0.3 gxkg-1, 0.2 gxkg-1, 0.1 gxkg-1, and placebo);
      and Part B, similar profiles after alternative NaHCO3 loading protocols (single
      morning dosage [SMD], single evening dosage [SED], and dosages ingested on 3
      consecutive evenings [CED]). Results from Part A are as follows. Blood buffering
      in the 0.1 gxkg-1 condition was significantly lower than the 0.2 g.kg-1 and 0.3
      gxkg-1 conditions (p < 0.002), but there was no significant differences between
      the 0.2 gxkg -1and 0.3 g.kg-1 conditions (p = 0.34). Although the blood buffering
      was relatively constant in the 0.1 and 0.2 conditions, it was significantly
      higher at 60 minutes than at 100 minutes and 120 minutes in the 0.3 gxkg-1
      condition (p < 0.05). Results from Part B are as follows. Blood buffering for SMD
      was significantly higher than for SED and CED (p < 0.05). Blood buffering in the
      SMD condition was significantly lower at 17:00 hours than at 11:00 hours (p =
      0.007). The single 0.2 and 0.3 gxkg-1 NaHCO3 dosages appeared to be the most
      effective for increasing blood-buffering capacity. The 0.2 gxkg-1 dosage is best
      ingested 40 to 50 minutes before exercise and the 0.3 gxkg-1 dosage 60 minutes
      before exercise.

PMID- 20040896
TI  - A comparison study of clinicopathologic characteristics of Southern California
      Asian American Non-small Cell Lung Cancer (NSCLC) patients by smoking status.
AB  - BACKGROUND: We previously reported that Asian ethnicity is a favorable prognostic
      factor for overall survival (OS) in non-small cell lung cancer (NSCLC) patients
      independent of smoking status. However, Asian ethnicity represents a diverse and
      heterogeneous population. In this report, we compared the clinicopathologic
      characteristics of Asian American NSCLC patient subgroups by smoking status.
      METHODS: Clinicopathologic characteristics of the five major Asian American NSCLC
      patient subgroups diagnosed between 1991 and 2005 from three Southern California
      counties were analyzed. Prognostic factors for OS were evaluated by Cox
      multivariate analysis. RESULTS: One thousand one hundred twenty-four NSCLC
      patients were analyzed: Filipino American (37.0%), Vietnamese American (32.8%),
      Japanese American (11.8%), Chinese American (11.7%), and Korean American (6.7%).
      A total of 25.7% of these patients were never smokers. With the exception of
      Japanese American, most of Asian American were native born. Median age of never
      smokers was marginally younger than ever smokers (66 years versus 68 years,
      respectively, p = 0.0507). The proportion of never smokers who were women was
      72.7% and ranged from the lowest among Korean American women (66.7%) to the
      highest among Japanese American women (84.2%). Among female patients, Vietnamese
      American patients had the highest proportion of being never smokers (65.5%).
      Significantly more never smokers (60.9%) than ever smokers (47.9%) presented with
      stage 4 disease. There was no statistical significant difference in OS between
      never smokers and ever smokers (11 versus 10 months; p = 0.3040). Tumor-related
      factors (stage and histologic differentiation) and treatment (surgery and
      chemotherapy) were independent prognostic factors for survival. CONCLUSIONS: We
      found no statistical significant difference in clinicopathologic features or
      survival outcome between individual Asian American subgroup when analyzed
      according to smoking status.

PMID- 20040897
TI  - Effect of nevirapine on the steady-state trough concentrations of atazanavir in
      HIV-infected patients receiving atazanavir/ritonavir.
AB  - MATERIAL AND METHODS: To evaluate the influence of nevirapine on atazanavir
      trough concentrations (Ctrough) in a group of HIV-infected patients, we performed
      an open-label pilot study enrolling patients receiving 300/100 mg
      atazanavir/ritonavir once daily for 2 weeks or longer. Nevirapine was added at a
      dose of 200 mg once daily from Days 0 to 14 and 200 mg twice daily from Days 14
      to 28. Atazanavir and nevirapine plasma Ctroughs were determined at Days 0 and
      28. Atazanavir Ctroughs were compared between Days 0 and 28. Atazanavir and
      nevirapine Ctroughs at Day 28 were compared with historical controls receiving
      either 400 mg atazanavir once daily or 200 mg nevirapine twice daily. RESULTS:
      Fourteen patients were enrolled and 11 completed the study. The geometric mean
      (range) atazanavir Ctrough decreased from 0.631 mg/L (range, 0.235-1.87 mg/L) at
      Day 0 to 0.316 mg/L (range, 0.142-1.109 mg/L) at Day 28 to give a geometric mean
      ratio of 0.59 (95% confidence interval, 0.38-0.80; P = 0.026); nonetheless, the
      atazanavir Ctrough remained higher than the minimum effective concentration in
      80% of the participants and higher than the median concentration in the control
      subjects receiving 400 mg atazanavir once daily without ritonavir (geometric mean
      ratio, 3.20; 95% confidence interval, 1.65-6.22; P = 0.001). The nevirapine
      Ctrough at Day 28 was slightly higher than in the historical controls on 200 mg
      nevirapine twice daily without atazanavir (geometric mean ratio, 1.46; 95%
      confidence interval, 1.04-2.06; P = 0.030). CONCLUSION: We conclude that
      coadministration of 300/100 mg atazanavir/ritonavir once daily plus 200 mg
      nevirapine twice daily was safe and well tolerated but resulted in a decrease of
      atazanavir Ctrough by nearly half. Therefore, monitoring atazanavir Ctrough is
      recommended in patients treated with this drug combination, and increasing the
      atazanavir dose might be necessary.

PMID- 20040898
TI  - A validated high-performance liquid chromatography-ultraviolet method for
      quantification of the CCR5 inhibitor maraviroc in plasma of HIV-infected
      patients.
AB  - Maraviroc is the first commercialized CCR5 inhibitor for HIV therapy. A new high
      performance liquid chromatography-ultraviolet method to quantify maraviroc
      concentrations in human plasma was developed and validated. The method is based
      on a protein precipitation procedure, with an acidic solution of acetonitrile
      (trifluoroacetic acid 0.1%) and quinoxaline as internal standard. The analytes
      were eluted using a gradient run in 15 minutes on an analytical C18 Luna column
      (150 mm x 4.6 mm ID) with a particle size of 5 mum. Maraviroc and internal
      standard were detected by UV at 193 nm and 352 nm, respectively. The calibration
      curve was linear up to 2500 ng/mL. The mean recovery of maraviroc was 96%. All
      validation data were in accordance with U.S. Food and Drug Administration
      requirements. The new high-performance liquid chromatography-ultraviolet method
      reported here could be used routinely to monitor plasma concentrations of
      maraviroc in healthy volunteers and HIV-infected patients.

PMID- 20040899
TI  - Hydroxyzine and cetirizine interfere with the PENTINA carbamazepine assay but not
      with the ADVIA CENTEUR carbamazepine assay.
AB  - Because of a published report indicating significant interference of hydroxyzine
      with the particle-enhanced turbidimetric inhibition immunoassay (PENTINA)
      carbamazepine assay, we investigated whether such interference can be avoided by
      using the ADVIA Centaur carbamazepine assay. Both the Dimension Vista analyzer
      and ADVIA Centaur analyzer are available from Siemens Diagnostics. Aliquots of a
      drug-free serum pool were supplemented with various concentrations of hydroxyzine
      or cetirizine (0.05 microg/mL to 20 microg/mL covering therapeutic and toxic
      levels in serum) followed by analysis using both assays. We observed significant
      apparent carbamazepine concentrations using the PENTINA assay but no apparent
      carbamazepine level using the ADVIA Centaur assay. Because crossreactivity should
      be studied in the presence of the primary analyte, we also prepared a serum
      carbamazepine pool from patients receiving carbamazepine and then supplemented
      aliquots of this pool with various amounts of hydroxyzine or cetirizine followed
      by reanalyzing carbamazepine concentration using both assays. We observed falsely
      elevated carbamazepine values using the PENTINA assay but no interference was
      observed using the ADVIA Centaur assay. However, the falsely elevated
      carbamazepine values using the PENTINA assay were clinically significant at
      hydroxyzine or cetirizine concentrations expected in patients with severe
      overdoses with these drugs. We conclude that the ADVIA Centaur carbamazepine
      assay is free from interference of both hydroxyzine and cetirizine.

PMID- 20040902
TI  - Frontline therapy for chronic lymphocytic leukemia patients.

PMID- 20040903
TI  - Improving the staging system in colorectal cancer.

PMID- 20040904
TI  - ALK inhibitors in lung cancer.

PMID- 20040905
TI  - Blood product transfusion and cancer prognosis.

PMID- 20040906
TI  - Anti-angiogenic therapy in renal cell carcinoma: Alone, in combination, or
      sequentially.

PMID- 20040907
TI  - First reported case of aplastic anemia occurring in a patient after acute
      promyelocytic leukemia in remission.

PMID- 20040908
TI  - Aplastic anemia surfacing after treatment of acute promyelocytic leukemia: The
      Dameshek riddle.

PMID- 20040909
TI  - Waldenstrom's macroglobulinemia: Recent advances in biology and therapy.
AB  - Waldenstrom's macroglobulinemia (WM) is a B-cell disorder characterized by bone
      marrow infiltration with clonal lymphoplasmacytic cells (LPCs), along with an
      immunoglobulin M monoclonal gammopathy. Recent studies have led to several
      insights into disease biology as well as the development of an international
      staging system. Patients with asymptomatic macroglobulinemia should be observed
      without therapy. Options for frontline therapy include alkylating agents,
      nucleoside analogs, and rituximab, either as monotherapy or in combination.
      Although objective responses are common, complete remissions are infrequent.
      Several novel agents including proteasome inhibitors and thalidomide, as well as
      high-dose chemotherapy and stem cell transplantation are being incorporated into
      the therapeutic armamentarium in WM and show promising activity. This report
      provides an update on recent advances in biology and treatment of this disease.

PMID- 20040910
TI  - Live dissection of Drosophila embryos: streamlined methods for screening mutant
      collections by antibody staining.
AB  - Drosophila embryos between stages 14 and 17 of embryonic development can be
      readily dissected to generate "fillet" preparations. In these preparations, the
      central nervous system runs down the middle, and is flanked by the body walls.
      Many different phenotypes have been examined using such preparations. In most
      cases, the fillets were generated by dissection of antibody-stained fixed whole
      mount embryos. These "fixed dissections" have some disadvantages, however. They
      are time-consuming to execute, and it is difficult to sort mutant (GFP-negative)
      embryos from stocks in which mutations are maintained over GFP balancer
      chromosomes. Since 2002, our group has been conducting deficiency and ectopic
      expression screens to identify ligands for orphan receptors. In order to do this,
      we developed streamlined protocols for live embryo dissection and antibody
      staining of collections containing hundreds of balanced lines. We have concluded
      that it is considerably more efficient to examine phenotypes in large collections
      of stocks by live dissection than by fixed dissection. Using the protocol
      described here, a single trained individual can screen up to 10 lines per day for
      phenotypes, examining 4-7 mutant embryos from each line under a compound
      microscope. This allows the identification of mutations conferring subtle, low
      penetrance phenotypes, since up to 70 hemisegments per line are scored at high
      magnification with a 40X water-immersion lens.

PMID- 20040911
TI  - Targeting of p53-transcriptional dysfunction by conditionally replicating
      adenovirus is not limited by p53-homologues.
AB  - A hallmark of human tumors is the loss of p53 or its transcriptional functions.
      In this study, we describe the generation of the conditionally replicating
      adenovirus Adp53sensor for the treatment of p53-dysfunctional tumors. p53
      selective attenuation of viral replication was achieved by using p53-dependent
      expression of the transcriptional repressor Gal4-KRAB that was directed against
      the adenoviral E1A locus. Adp53sensor shows efficient replication in p53
      dysfunctional, but not in p53-active cells. In p53-dysfunctional cells, p53
      analogous transcriptional activity by other p53 family members was not sufficient
      to compromise replication of Adp53sensor. In comparison with a genetically
      similar, but p53-insensitive virus, Adp53sensor replication was inhibited after
      systemic infection of p53-wt-mice, but not in p53-ko-mice thus confirming the
      correct function of the chosen approach. Adp53sensor showed efficient lytic and
      replicative properties in all investigated cells with p53-dysfunction and
      successfully inhibited the growth of subcutaneous xenotransplants in vivo. We
      further demonstrated that intravenous injection of Adp53sensor lead to
      significantly reduced liver damage compared to the control virus. Together, our
      data show that Adp53sensor is an oncolytic, p53-selective adenovirus for
      efficient treatment of p53-dysfunctional tumors with a favorable toxicity
      profile. Moreover, Adp53sensor provides a strategy that should be applicable to
      other transcriptionally regulated DNA viruses.

PMID- 20040912
TI  - Immune responses to AAV in canine muscle monitored by cellular assays and
      noninvasive imaging.
AB  - We previously demonstrated that direct intramuscular injection of rAAV2 or rAAV6
      in wild-type dogs resulted in robust T-cell responses to viral capsid proteins,
      and others have shown that cellular immunity to adeno-associated virus (AAV)
      capsid proteins coincided with liver toxicity and elimination of transgene
      expression in a human trial of hemophilia B. Here, we show that the heparin
      binding ability of a given AAV serotype does not determine the induction of T
      cell responses following intramuscular injection in dogs, and identify multiple
      epitopes in the AAV capsid protein that are recognized by T cells elicited by AAV
      injection. We also demonstrate that noninvasive magnetic resonance imaging (MRI)
      can accurately detect local inflammatory responses following intramuscular rAAV
      injection in dogs. These studies suggest that pseudotyping rAAV vectors to remove
      heparin-binding activity will not be sufficient to abrogate immunogenicity, and
      validate the utility of enzyme-linked immunosorbent spot (ELISpot) assay and MRI
      for monitoring immune and inflammatory responses following intramuscular
      injection of rAAV vectors in preclinical studies in dogs. These assays should be
      incorporated into future human clinical trials of AAV gene therapy to monitor
      immune responses.

PMID- 20040913
TI  - Directed evolution of a novel adeno-associated virus (AAV) vector that crosses
      the seizure-compromised blood-brain barrier (BBB).
AB  - DNA shuffling and directed evolution were employed to develop a novel adeno
      associated virus (AAV) vector capable of crossing the seizure-compromised blood
      brain barrier (BBB) and transducing cells in the brain. Capsid DNA from AAV
      serotypes 1-6, 8, and 9 were shuffled and recombined to create a library of
      chimeric AAVs. One day after kainic acid-induced limbic seizure activity in rats,
      the virus library was infused intravenously (i.v.), and 3 days later, neuron-rich
      cells were mechanically dissociated from seizure-sensitive brain sites, collected
      and viral DNA extracted. After three cycles of selection, green fluorescent
      protein (GFP)-packaged clones were administered directly into brain or i.v. 1 day
      after kainic acid-induced seizures. Several clones that were effective after
      intracranial administration did not transduce brain cells after the i.v.
      administration. However, two clones (32 and 83) transduced the cells after direct
      brain infusion and after i.v. administration transduced the cells that were
      localized to the piriform cortex and ventral hippocampus, areas exhibiting a
      seizure-compromised BBB. No transduction occurred in areas devoid of BBB
      compromise. Only one parental serotype (AAV8) exhibited a similar expression
      profile, but the biodistribution of 32 and 83 diverged dramatically from this
      parental serotype. Thus, novel AAV vectors have been created that can selectively
      cross the seizure-compromised BBB and transduce cells.

PMID- 20040914
TI  - Arbaclofen placarbil decreases postprandial reflux in patients with
      gastroesophageal reflux disease.
AB  - OBJECTIVES: Arbaclofen placarbil (AP), previously designated as XP19986, is an
      investigational prodrug of the active R-isomer of baclofen, a gamma-aminobutyric
      acid agonist reflux inhibitor. The aim of this study was to assess the efficacy
      and safety of AP for decreasing meal-induced reflux episodes in patients with
      gastroesophageal reflux disease (GERD). METHODS: We conducted a multicenter,
      randomized, double-blind, crossover study comparing single doses of AP with
      placebo. Different patients were enrolled at each of four escalating AP doses:
      10, 20, 40, and 60 mg. Enrolled patients had GERD symptoms at least three times a
      week and 20 reflux episodes on impedance/pH monitoring over a period of 2 h.
      During study visits separated by periods of 3-7 days, patients received single
      doses of AP or placebo, followed by high-fat meals 2 and 6 h after treatment. The
      primary end point was the number of reflux episodes over 12 h after treatment.
      RESULTS: A total of 50 patients were treated; efficacy analysis included 44
      patients who received both AP and placebo and had technically satisfactory
      impedance/pH data. For the combined data from all dose cohorts, there was a
      statistically significant (P=0.01) decrease in reflux episodes over 12 h after
      treatment with AP compared with placebo. The mean (s.d.) number of reflux
      episodes over 12 h after AP treatment was 50.5 (27.2), with a mean reduction of
      10.4 (23.9) episodes (17%) compared with placebo, for which a mean (s.d.) number
      of 60.9 (35.3) episodes was observed. Heartburn events associated with reflux
      were reduced during treatment with AP compared with placebo. AP seemed to be the
      most efficacious in the 60-mg dose group, and was well tolerated at all dose
      levels. CONCLUSIONS: AP decreased reflux and associated symptoms with good
      tolerability in patients with GERD.

PMID- 20040915
TI  - Non-alcoholic fatty liver disease in liver transplant recipients: another story
      of "seed and soil".
AB  - OBJECTIVES: Fatty liver disease is a potential long-term complication of liver
      transplantation (LT). We therefore aimed to determine the prevalence and risk
      factors of liver steatosis in a large population of adult post-LT patients.
      METHODS: We evaluated the clinical, biological, histological, and evolutive
      features of patients with a diagnosis of steatosis made at liver biopsy
      examination during post-LT follow-up. Risk factors were analyzed by univariate
      and multivariate analysis. RESULTS: In total, 1,596 liver biopsies from 599
      patients were available. Recurrent liver disease was present in 178 patients. A
      histological diagnosis of steatosis was made in 131 (31.1%) of the remaining 421
      patients (51.1% had normal liver tests): 53% had grade 1, 31% grade 2, and 16%
      grade 3 steatosis. Perisinusoidal fibrosis was present in 38 patients (29.0%).
      Histological lesions were consistent with the diagnosis of non-alcoholic
      steatohepatitis (NASH) in 5 patients (3.8%). At the end of follow-up, cirrhosis
      or extensive fibrosis was observed in 3 patients (2.25%). Multivariate analysis
      showed that seven factors (post-LT obesity, tacrolimus-based regimen, diabetes
      mellitus, hyperlipidemia, arterial hypertension, alcoholic cirrhosis as primary
      indication for LT, and pre-transplant liver graft steatosis) were risk factors
      for post-LT steatosis. When zero, one, two, three, four, five, and six factors
      were present, steatosis occurred in 6.0, 12.0, 22.1, 29.9, 65.5, 81.5, and
      100.0%, respectively. CONCLUSIONS: Liver steatosis is a frequent late
      complication of LT; its development depends on a combination of host and graft
      factors. LT is therefore an interesting model to study the natural history and
      the determinants of liver steatosis.

PMID- 20040916
TI  - Breaking the wall: targeting of the endothelium by pathogenic bacteria.
AB  - The endothelium lining blood and lymphatic vessels is a key barrier separating
      body fluids from host tissues and is a major target of pathogenic bacteria.
      Endothelial cells are actively involved in host responses to infectious agents,
      producing inflammatory cytokines, controlling coagulation cascades and regulating
      leukocyte trafficking. In this Review, a range of bacteria and bacterial toxins
      are used to illustrate how pathogens establish intimate interactions with
      endothelial cells, triggering inflammatory responses and coagulation processes
      and modifying endothelial cell plasma membranes and junctions to adhere to their
      surfaces and then invade, cross and even disrupt the endothelial barrier.

PMID- 20040920
TI  - Comorbidity and confounding in end-stage renal disease.
AB  - In the epidemiologic study of end-stage renal disease (ESRD), accurate adjustment
      for comorbidity is essential to controlling bias in the comparison of outcomes
      across groups of patients or dialysis facilities. Liu et al. derive and validate
      a novel comorbidity index using data from the United States Renal Data System.
      This novel index represents an important tool for observational research in ESRD
      but will not by itself overcome the potential problems of residual and unmeasured
      confounding in observational research.

PMID- 20040917
TI  - Model or meal? Farm animal populations as models for infectious diseases of
      humans.
AB  - In recent decades, theory addressing the processes that underlie the dynamics of
      infectious diseases has progressed considerably. Unfortunately, the availability
      of empirical data to evaluate these theories has not grown at the same pace.
      Although laboratory animals have been widely used as models at the organism
      level, they have been less appropriate for addressing issues at the population
      level. However, farm animal populations can provide empirical models to study
      infectious diseases at the population level.

PMID- 20040921
TI  - Hydrogen: another gas with therapeutic potential.
AB  - Cardinal and colleagues describe the use of molecular hydrogen, the most abundant
      molecule in the universe, as a treatment for chronic allograft nephropathy (CAN)
      in a rat model of kidney transplantation. They demonstrate that the addition of
      hydrogen to the drinking water results in a decrease in the severity of CAN and
      increased graft survival, and they provide evidence that the mechanism of action
      could be due to a reduction in reactive oxygen species.

PMID- 20040923
TI  - Regarding 'Calcium channel blocker-induced chylous ascites in peritoneal
      dialysis'.

PMID- 20040924
TI  - Intrathoracic kidney with right Bochdalek's hernia.

PMID- 20040925
TI  - The Case | Best not shaken or stirred! Chronic lymphocytic leukemia and
      hyperkalemia.

PMID- 20040926
TI  - Glial dysfunction in abstinent methamphetamine abusers.
AB  - Persistent neurochemical abnormalities in frontal brain structures are believed
      to result from methamphetamine use. We developed a localized (13)C magnetic
      resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify
      selectively glial metabolic flux rate in frontal brain of normal subjects and a
      cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate
      concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter
      of frontal brain of normal volunteers and recovering methamphetamine-abusing
      subjects (P>0.1). However, glial (13)C-bicarbonate production rate from [1
      (13)C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was
      significantly reduced in frontal brain of abstinent methamphetamine-addicted
      women (methamphetamine 0.04 micromol/g per min (N=5) versus controls 0.11
      micromol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial
      TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises
      10% of total cerebral metabolic rate may impact operation of the neuronal glial
      glutamate cycle and result in accumulation of frontal brain glutamate, as
      observed in these recovering methamphetamine abusers. Although these are the
      first studies to define directly an abnormality in glial metabolism in human
      methamphetamine abuse, sequential studies using analogous (13)C MRS methods may
      determine 'cause and effect' between glial failure and neuronal injury.

PMID- 20040927
TI  - Neurovascular coupling in rat brain operates independent of hemoglobin
      deoxygenation.
AB  - Recently, a universal, simple, and fail-safe mechanism has been proposed by which
      cerebral blood flow (CBF) might be coupled to oxygen metabolism during neuronal
      activation without the need for any tissue-based mechanism. According to this
      concept, vasodilation occurs by local erythrocytic release of nitric oxide or ATP
      wherever and whenever hemoglobin is deoxygenated, directly matching oxygen demand
      and supply in every tissue. For neurovascular coupling in the brain, we present
      experimental evidence challenging this view by applying an experimental regime
      operating without deoxy-hemoglobin. Hyperbaric hyperoxygenation (HBO) allowed us
      to prevent hemoglobin deoxygenation, as the oxygen that was physically dissolved
      in the tissue was sufficient to support oxidative metabolism. Regional CBF and
      regional cerebral blood oxygenation were measured using a cranial window
      preparation in anesthetized rats. Hemodynamic and neuronal responses to
      electrical forepaw stimulation or cortical spreading depression (CSD) were
      analyzed under normobaric normoxia and during HBO up to 4 ATA (standard
      atmospheres absolute). Inconsistent with the proposed mechanism, during HBO, CBF
      responses to functional activation or CSD were unchanged. Our results show that
      activation-induced CBF regulation in the brain does not operate through the
      release of vasoactive mediators on hemoglobin deoxygenation or through a tissue
      based oxygen-sensing mechanism.

PMID- 20040928
TI  - High-affinity dopamine D2/D3 PET radioligands 18F-fallypride and 11C-FLB457: a
      comparison of kinetics in extrastriatal regions using a multiple-injection
      protocol.
AB  - (18)F-Fallypride and (11)C-FLB457 are commonly used PET radioligands for imaging
      extrastriatal dopamine D(2)/D(3) receptors, but differences in their in vivo
      kinetics may affect the sensitivity for measuring subtle changes in receptor
      binding. Focusing on regions of low binding, a direct comparison of the kinetics
      of (18)F-fallypride and (11)C-FLB457 was made using a MI protocol. Injection
      protocols were designed to estimate K(1), k(2), f(ND)k(on), B(max), and k(off) in
      the midbrain and cortical regions of the rhesus monkey. (11)C-FLB457 cleared from
      the arterial plasma faster and yielded a ND space distribution volume (K(1)/k(2))
      that is three times higher than (18)F-fallypride, primarily due to a slower k(2)
      (FAL:FLB; k(2)=0.54 min(-1):0.18 min(-1)). The dissociation rate constant,
      k(off), was slower for (11)C-FLB457, resulting in a lower K(Dapp) than (18)F
      fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D(2)/D(3) binding could be
      detected in the cerebellum for (11)C-FLB457 but not (18)F-fallypride. Both
      radioligands can be used to image extrastriatal D(2)/D(3) receptors, with (11)C
      FLB457 providing greater sensitivity to subtle changes in low-receptor-density
      cortical regions and (18)F-fallypride being more sensitive to endogenous dopamine
      displacement in medium-to-high-receptor-density regions. In the presence of
      specific D(2)/D(3) binding in the cerebellum, reference region analysis methods
      will give a greater bias in BP(ND) with (11)C-FLB457 than with (18)F-fallypride.

PMID- 20040929
TI  - A systematic review and meta-analysis of erythropoietin in experimental stroke.
AB  - Erythropoietin (EPO) has shown promise as a neuroprotectant in animal models of
      ischemic stroke. EPO is thought not only to protect neurons from cell death, but
      also to promote regeneration after stroke. Here, we report a systematic review
      and meta-analysis of the efficacy of EPO in animal models of focal cerebral
      ischemia. Primary outcomes were infarct size and neurobehavioral outcome.
      Nineteen studies involving 346 animals for infarct size and 425 animals for
      neurobehavioral outcome met our inclusion criteria. Erythropoietin improved
      infarct size by 30.0% (95% CI: 21.3 to 38.8) and neurobehavioral outcome by 39.8%
      (33.7 to 45.9). Studies that randomized to treatment group or that blinded
      assessment of outcome showed lower efficacy. Erythropoietin was tested in animals
      with hypertension in no studies reporting infarct size and in 7.5% of the animals
      reporting neurobehavioral outcome. These findings show efficacy for EPO in
      experimental stroke, but when the impact of common sources of bias are
      considered, this efficacy falls, suggesting we may be overestimating its
      potential benefit. As common human co-morbidities may reduce therapeutic
      efficacy, broader testing to delineate the range of circumstances in which EPO
      works best would be beneficial.

PMID- 20040930
TI  - Investigating the American Time Use Survey from an exposure modeling perspective.
AB  - This paper describes an evaluation of the US Bureau of Labor Statistics' American
      Time Use Survey (ATUS) for potential use in modeling human exposures to
      environmental pollutants. The ATUS is a large, on-going, cross-sectional survey
      of where Americans spend time and what activities they undertake in those
      locations. The data are reported as a series of sequential activities over a 24-h
      time period--a "diary day"--starting at 0400 hours. Between 12,000 and 13,000
      surveys are obtained each year and the Bureau has plans to continue ATUS for the
      foreseeable future. The ATUS already has about 73,000 diary days of data, more
      than twice as many as that which currently exists in the US Environmental
      Protection Agency's (EPA) "Consolidated Human Activity Database" (CHAD) that the
      Agency uses for exposure modeling purposes. There are limitations for using ATUS
      in modeling human exposures to environmental pollutants. The ATUS does not report
      the location for a number of activities regarded as "personal." For 2006,
      personal activities with missing location information totaled 572 min/day, on
      average, for survey participants: about 40% of their day. Another limitation is
      that ATUS does not distinguish between indoor and outdoor activities at home, two
      of the traditional locational demarcations used in human exposure modeling. This
      lack of information affects exposure estimates to both indoor and outdoor air
      pollutants and potentially affects non-dietary ingestion estimates for children,
      which can vary widely depending on whether or not a child is indoors. Finally, a
      detailed analysis of the work travel activity in a subsample from ATUS 2006
      indicates that the coding scheme is not fully consistent with a CHAD-based
      exposure modeling approach. For ATUS respondents in this subsample who reported
      work as an activity, roughly 48% of their days were missing work travel at one or
      both ends of the work shift or reported within work-shift travel inconsistently.
      An extensive effort would be needed to recode work travel data from ATUS for
      EPA's exposure modeling purposes.

PMID- 20040931
TI  - Bayesian hierarchical modeling of cardiac response to particulate matter
      exposure.
AB  - Studies have linked increased levels of particulate air pollution to decreased
      autonomic control, as measured by heart rate variability (HRV), particularly in
      susceptible populations such as the elderly. In this study, we use data obtained
      from the 1998 USEPA epidemiology-exposure longitudinal panel study of elderly
      adults in a Baltimore retirement home to examine the relationship between HRV and
      PM2.5 personal exposure. We consider PM2.5 personal exposure in the aggregate and
      personal exposure to the components of PM2.5 as estimated in two ways using
      receptor models. We develop a Bayesian hierarchical model for HRV as a function
      of personal exposure to PM2.5, which integrates HRV measurements and data
      obtained from personal, indoor and outdoor PM2.5 monitoring and meteorological
      data. We found a strong relationship between decreased HRV (HF, LF, r-MSSD and
      SDNN) and total personal exposure to PM2.5 at a lag of 1 day. Using personal
      exposure monitoring (PEM) apportionment results, we examined the relative
      importance of ambient and non-ambient personal PM2.5 exposure to HRV and found
      the effect of internal non-ambient sources of PM2.5 on HRV to be minimal. Using
      the PEM apportionment data, a consistent effect of soil at short time scales (lag
      0) was found across all five HRV measures, and an effect of sulfate on HRV was
      seen for HF and r-MSSD at the moving average of lags 0 and 1 days. Modeling of
      ambient site apportionment data indicated effects of nitrate on HRV at lags of 1
      day, and moving averages of days 0 and 1 and days 0-2 for all but the ratio
      LF/HF. Sulfate had an effect on HRV at a lag of 1 day for four HRV measures (HF,
      LF, r-MSSD, SDNN) and for LF/HF at a moving average of days 0-2.

PMID- 20040933
TI  - Four decades of Indian Journal of Pharmacology: An overview.

PMID- 20040932
TI  - Determinants of polycyclic aromatic hydrocarbon levels in house dust.
AB  - Estimation of human exposures to polycyclic aromatic hydrocarbons (PAHs) is often
      desired for the epidemiological studies of cancer. One way to obtain information
      about indoor levels of PAHs is to measure these chemicals in house dust. In this
      study, we evaluated the predictive value of self-reported and geographic data for
      estimating measured levels of nine PAHs in house dust from 583 households in the
      Northern California Childhood Leukemia Study (NCCLS). Using multivariable linear
      regression models, we evaluated the effects on house-dust PAH concentrations from
      the following covariates: residential heating sources, smoking habits, house
      characteristics, and outdoor emission sources. House dust was collected from 2001
      to 2007, using both high-volume surface samplers and household vacuum cleaners,
      and was analyzed for nine PAHs using gas chromatography-mass spectrometry. All
      nine PAHs were detected in more than 93% of dust samples, with median
      concentrations ranging from 14 to 94 ng/g dust. Statistically significant effects
      on PAH concentrations in house dust were found for gas heating, outdoor PAH
      concentrations, and residence age. Yet, the optimal regression model only
      explained 15% of the variation in PAH levels in house dust. As self-reported data
      and outdoor PAH sources were only marginally predictive of observed PAH levels,
      we recommend that PAH concentrations be measured directly in dust samples for use
      in epidemiological studies.

PMID- 20040934
TI  - Novel immunobiologics for psoriasis.
AB  - Psoriasis is one of the most common human skin diseases and is considered to have
      key genetic contributions. It is characterized by excessive growth and aberrant
      differentiation of keratinocytes, but is reversible with appropriate therapy with
      the possibilities of recurrence. The trigger of the keratinocyte response is
      thought to be the activation of the cellular immune system with T cells,
      dendritic cells and various immune related cytokines and chemokines being
      implicated in pathogenesis. Immunosuppressants like cyclosporine and methotrexate
      were used earlier in the treatment of psoriasis, however their use was associated
      with severe adverse effects due to down regulation of immune system. The most
      recent advances in therapies for psoriasis target specific immune components of
      psoriasis and promise to have high therapeutic efficacy with low adverse effects.
      This review focuses on the novel therapies aimed to specifically modulate the
      dysregulated immune system with minimal adverse effects.

PMID- 20040935
TI  - Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in
      non insulin dependent diabetes mellitus induced rats.
AB  - OBJECTIVE: To study the effect of Trichosanthes cucumerina Linn. on non insulin
      dependent diabetes mellitus induced rats. MATERIALS AND METHODS: Non Insulin
      Dependent Diabetes Mellitus (NIDDM) was induced by administering streptozotocin
      (90 mg/kg, i.p.) in neonatal rat model. NIDDM animals were treated with aqueous
      extract of Trichosanthes cucumerina (100 mg/kg/day) orally for six weeks.
      Parameters such as fasting blood glucose, Oral Glucose Tolerance Test (OGTT) and
      tissue glycogen content were evaluated. RESULTS: Aqueous extract of Trichosanthes
      cucumerina significantly (P<0.01) decreased the elevated blood glucose of NIDDM
      induced rats. OGTT of NIDDM animals showed glucose intolerance. Blood glucose of
      diabetic animals reached peak at 45 min and remains high even after 2h. In case
      of Trichosanthes cucumerina treated group, the blood glucose reached peak level
      at 30 min, followed by decrease in glucose level up to 2h. The drug has
      significantly (P<0.01) reduced the postprandial blood glucose of diabetic
      animals. Glycogen content of insulin dependent tissues such as liver and skeletal
      muscle was found to be improved by 62% and 58.8% respectively with Trichosanthes
      cucumerina as compared to NIDDM control. CONCLUSION: Studies revealed that,
      Trichosanthes cucumerina possess antidiabetic activity. The drug improved the
      oral glucose tolerance of NIDDM subjects. Increase in tissue glycogen content
      indicates the effect of the drug on the uptake of glucose by the peripheral
      tissues to reduce insulin resistance of NIDDM.

PMID- 20040936
TI  - Immunomodulatory effect of Tinospora cordifolia extract in human immuno
      deficiency virus positive patients.
AB  - OBJECTIVES: To assess the safety and efficacy of TCE in human immuno-deficiency
      virus positive patients. MATERIALS AND METHODS: Efficacy of Tinospora cordifolia
      extract (TCE) in HIV positive patients was assessed in randomized double blind
      placebo controlled trial. 68 HIV positive participants were randomly assigned to
      two groups to receive either TCE or placebo for six months. After clinical
      examination TLC, DLC, ESR, platelet count, hemoglobin and CD4 count were done.
      The hematological investigations were repeated at bimonthly intervals and CD4
      count was repeated at the end of the study. Patients were clinically reviewed at
      monthly intervals for compliance, refill and ADR monitoring. The drugs were
      decoded at the end of the trial. RESULTS: TCE treatment caused significant
      reduction in eosinophil count and hemoglobin percentage. 60% patients receiving
      TCE and 20% on placebo reported decrease in the incidence of various symptoms
      associated with disease. Some of the common complaints reported by patients on
      TCE were anorexia, nausea, vomiting and weakness. CONCLUSION: Tinospora
      cordifolia extract, a plant derived immunostimulant, significantly affected the
      symptoms of HIV. This was validated by clinical evaluation. However not all of
      the objective parameters studied by us, back this up. Tinospora cordifolia could
      be used as an adjunct to HIV/AIDS management.

PMID- 20040937
TI  - In vivo antimalarial activity of ethanolic leaf extract of Stachytarpheta
      cayennensis.
AB  - OBJECTIVE: To evaluate the in vivo antiplasmodial activity of the ethanol leaf
      extract of Stachytarpheta cayennensis in the treatment of various ailment in
      Niger Delta region of Nigeria, in Plasmodium berghei infected mice. MATERIALS AND
      METHODS: The ethanolic leaf extract of Stachytarpheta cayennensis (90-270
      mg/kg/day) was screened for blood schizonticidal activity against chloroquine
      sensitive Plasmodium berghei berghei in mice. The schizonticidal effect during
      early and established infections was investigated. RESULT: Stachytarpheta
      cayennensis (90-270 mg/kg/day) exhibited significant (P< 0.05) blood
      schizonticidal activity both in 4-day early infection test and in established
      infection with a considerable mean survival time comparable to that of the
      standard drug, chloroquine, 5 mg/kg/day. CONCLUSION: The leaf extract possesses
      significant (P< 0.05) antiplasmodial activity which confirms it's use in
      folkloric medicine in the treatment of malaria.

PMID- 20040938
TI  - Comparative evaluation of some flavonoids and tocopherol acetate against the
      systemic toxicity induced by sulphur mustard.
AB  - OBJECTIVE: To evaluate the protective value of quercetin, gossypin, Hippophae
      rhamnoides (HR) flavone and tocopherol acetate against the systemic toxicity of
      percutaneously administered sulphur mustard (SM) in mice. MATERIALS AND METHODS:
      Quercetin, gossypin, HR flavone or tocopherol acetate (200 mg/kg, i.p.) were
      administered just before percutaneous administration of SM and protection against
      the SM lethality was evaluated. In another experiment quercetin, gossypin, HR
      flavone or tocopherol acetate were administered against 2 LD(50) SM. The animals
      were sacrificed seven days post SM administration and various biochemical
      parameters were estimated. RESULTS: The protection against the lethality of SM
      was very good with the flavonoids (quercetin = 4.7 folds; gossypin = 6.7 folds
      and HR flavone = 5.6 folds), compared to no protection with tocopherol acetate
      (0.7 fold). SM (2 LD(50)) showed decrease in reduced and oxidised glutathione
      (GSH and GSSG) levels, and an increase in malondialdehyde level (MDA). Oxidative
      stress enzymes like glutathione peroxidase, glutathione reductase and superoxide
      dismutase were significantly decreased. The total antioxidant status was also
      significantly decreased. Additionally, there was a significant increase in red
      blood corpuscles and hemoglobin content. All the flavonoids significantly
      protected the GSH, GSSG and MDA, and also the hematological variables. Tocopherol
      acetate failed to offer any protection in those parameters. Gossypin protected
      glutathione peroxidase, while HR flavone protected both glutathione reductase and
      glutathione peroxidase significantly. The decrease in body weight induced by SM
      and the histological lesions in liver and spleen were also significantly
      protected by the flavonoids but not by tocopherol acetate. CONCLUSION: The
      present study supports that SM induces oxidative stress and flavonoids are
      promising cytoprotectants against this toxic effect.

PMID- 20040939
TI  - Polyamines: Potential anti-inflammatory agents and their possible mechanism of
      action.
AB  - OBJECTIVE: To evaluate the anti-inflammatory activity of exogenously administered
      polyamines on experimentally induced acute and chronic inflammation in wistar
      rats and to elucidate their possible mechanism of action. MATERIALS AND METHODS:
      The in vivo anti-inflammatory activity of polyamines was studied using acute
      (carrageenin paw edema), sub-acute (cotton pellet granuloma) and chronic
      (Freund's adjuvant induced arthritis) models of inflammation. The biochemical
      parameters like liver lipid peroxides, SGOT and SGPT were also measured. RESULTS:
      Polyamines exhibited significant anti-inflammatory activity in acute, sub-acute
      and chronic models of inflammation. Polyamines treatment inhibited the increase
      in lipid peroxides in liver and the serum concentration of marker enzymes
      (glutamate oxaloacetate transferase and glutamate pyruvate transferase) during
      inflammation. CONCLUSION: Polyamines possess anti-inflammatory activity in acute
      and chronic inflammation which can be attributed to their anti-oxidant and /or
      lysosomal stabilization properties.

PMID- 20040940
TI  - Evalution of anti-ulcer activity of Polyalthia longifolia (Sonn.) Thwaites in
      experimental animals.
AB  - OBJECTIVE: To evaluate the anti-ulcer activity of ethanol extract of leaves of
      Polyalthia longifolia (Sonn.) Thwaites. MATERIALS AND METHODS: The ethanol
      extract of Polyalthia longifolia was investigated for its anti-ulcer activity
      against aspirin plus pylorous ligation induced gastric ulcer in rats, HCl 
      Ethanol induced ulcer in mice and water immersion stress induced ulcer in rats at
      300 mg/kg body weight.p.o. RESULTS: A significant (P < 0.01, P < 0.001) anti
      ulcer activity was observed in all the models. Pylorous ligation showed
      significant (P< 0.01) reduction in gastric volume, free acidity and ulcer index
      as compared to control. It also showed 89.71% ulcer inhibition in HCl- Ethanol
      induced ulcer and 95.3% ulcer protection index in stress induced ulcer.
      CONCLUSION: This present study indicates that P. longifolia leaves extract have
      potential anti ulcer activity in the three models tested.

PMID- 20040941
TI  - Evaluation of antidepressant activity of tramadol in mice.
AB  - OBJECTIVE: To evaluate antidepressant like effect of tramadol in mice. MATERIALS
      AND METHODS: Tramadol was administered at three different doses (10,20 and 40
      mg/kg, i.p) once daily for 7 days to Swiss albino mice of either sex. The
      immobility period of control and drug treated mice were recorded in tail
      suspension test (TST).The antidepressant effect of tramadol was compared to that
      of fluoxetine (20 mg/kg, i.p), administered for seven days. RESULTS: Tramadol
      produced significant antidepressant effect at all the doses, as indicated by
      reduction in immobility times as compared to control. The efficacy of tramadol at
      doses of 20 and 40 mg/kg was comparable with that of fluoxetine. Tramadol at 10
      mg/kg dose showed significantly less antidepressant activity compared to
      fluoxetine. CONCLUSION: The results of the present study indicate antidepressant
      like activity of tramadol.

PMID- 20040942
TI  - The concept of personal drugs in the undergraduate pharmacology practical
      curriculum.

PMID- 20040943
TI  - Neglected tropical diseases: Need for sensitization of medical students.

PMID- 20040944
TI  - Writing an effective manuscript: Editor's perspective.

PMID- 20040945
TI  - Role of pharmacogenomics in drug discovery and development.
AB  - Pharmacogenetics and pharmacogenomics are two major emerging trends in medical
      sciences, which influence the success of drug development and therapeutics. In
      current times, though pharmacogenetic studies are being done extensively for
      research, its application for drug development needs to get started on a large
      scale. The major determinants of success of a new drug compound, viz safety and
      efficacy, have become more predictable, with the advent of pharmacogenetic
      studies. There is a need felt for pharmacogenomic studies, where the effects of
      multiple genes are assessed with the study of entire genome.Pharmacogenetic
      studies can be used at various stages of drug development. The effect of drug
      target polymorphisms on drug response can be assessed and identified. In clinical
      studies, pharmacogenetic tests can be used for stratification of patients based
      on their genotype, which corresponds to their metabolizing capacity. This
      prevents the occurrence of severe adverse drug reactions and helps in better
      outcome of clinical trials. This can also reduce attrition of drug compounds.
      Further, the variations in drug response can be better studied with the wider
      application of pharmacogenomic methods like genome wide scans, haplotype analysis
      and candidate gene approaches. The cost of pharmacogenetic testing has become
      very low, with the advent of newer high throughput genotyping systems. However,
      the cost of pharmacogenomic methods continues to be very high. As the treatment
      with several drugs is being more and more pharmacogeneticaly guided (e.g.
      warfarin and irinotecan), the FDA has laid down guidelines for pharmaceutical
      firms regarding submission of pharmacogenetic data for their drug products in
      labelling.

PMID- 20040946
TI  - Burn wound healing property of Cocos nucifera: An appraisal.
AB  - OBJECTIVES: The study was undertaken to evaluate the burn wound healing property
      of oil of Cocos nucifera and to compare the effect of the combination of oil of
      Cocos nucifera and silver sulphadiazine with silver sulphadiazine alone.
      MATERIALS AND METHODS: Partial thickness burn wounds were inflicted upon four
      groups of six rats each. Group I was assigned as control, Group II received the
      standard silver sulphadiazine. Group III was given pure oil of Cocos nucifera ,
      and Group IV received the combination of the oil and the standard. The parameters
      observed were epithelialization period and percentage of wound contraction.
      RESULTS: It was noted that there was significant improvement in burn wound
      contraction in the group treated with the combination of Cocos nucifera and
      silver sulphadiazine. The period of epithelialization also decreased
      significantly in groups III and IV. CONCLUSION: It is concluded that oil of Cocos
      nucifera is an effective burn wound healing agent.

PMID- 20040947
TI  - In vitro antioxidant activity of pet ether extract of black pepper.
AB  - OBJECTIVE: To investigate the in vitro antioxidant activity of different
      fractions (R1, R2 and R3) obtained from pet ether extract of black pepper fruits
      (Piper nigrum Linn.) MATERIALS AND METHODS: The fractions R1, R2 and R3 were
      eluted from pet ether and ethyl acetate in the ratio of 6:4, 5:5 and 4:6,
      respectively. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radical, superoxide anion
      radical, nitric oxide radical, and hydroxyl radical scavenging assays were
      carried out to evaluate the antioxidant potential of the extract. RESULTS: The
      free radical scavenging activity of the different fractions of pet ether extract
      of P. nigrum (PEPN) increased in a concentration dependent manner. The R3 and R2
      fraction of PEPN in 500 microg/ml inhibited the peroxidation of a linoleic acid
      emulsion by 60.48+/-3.33% and 58.89+/-2.51%, respectively. In DPPH free radical
      scavenging assay, the activity of R3 and R2 were found to be almost similar. The
      R3 (100microg/ml) fraction of PEPN inhibited 55.68+/-4.48% nitric oxide radicals
      generated from sodium nitroprusside, whereas curcumin in the same concentration
      inhibited 84.27+/-4.12%. Moreover, PEPN scavenged the superoxide radical
      generated by the Xanthine/Xanthine oxidase system. The fraction R2 and R3 in the
      doses of 1000microg/ml inhibited 61.04+/-5.11% and 63.56+/-4.17%, respectively.
      The hydroxyl radical was generated by Fenton's reaction. The amounts of total
      phenolic compounds were determined and 56.98 microg pyrocatechol phenol
      equivalents were detected in one mg of R3. CONCLUSIONS: P. nigrum could be
      considered as a potential source of natural antioxidant.

PMID- 20040948
TI  - The effect of aqueous extract of Embelia ribes Burm on serum homocysteine, lipids
      and oxidative enzymes in methionine induced hyperhomocysteinemia.
AB  - OBJECTIVE: The present study was designed to evaluate the effect of the aqueous
      extract of Embelia ribes Burm fruits on methionine-induced hyperhomocysteinemia,
      hyperlipidemia and oxidative stress in albino rats. MATERIALS AND METHODS: Adult
      male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100
      and 200 mg/kg, p.o.) for 30 days. Hyperhomocysteinemia was induced by methionine
      treatment (1 g/kg, p.o.) for 30 days and folic acid (100 mg/kg, p.o.) was used as
      a standard drug. The animals were evaluated for various biochemical parameters in
      serum and brain homogenates, followed by histopathological studies at the end of
      the study. RESULTS: Administration of methionine (1 g/kg, p.o.) for 30 days to
      vehicle control rats produced significant increase (P < 0.01) in homocysteine,
      lactate dehydrogenase (LDH), total cholesterol, triglycerides, low density
      lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) levels in serum and
      lipid peroxides (LPO) levels in brain homogenates, with reduction in high density
      lipoprotein (HDL-C) levels in serum, and glutathione (GSH) content in brain
      homogenates, as compared to vehicle control rats. Administration of the aqueous
      extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days, to
      hyperhomocysteinemic rats, significantly (P < 0.01) decreased the levels of
      homocysteine, LDH, total cholesterol, triglycerides, LDL-C and VLDL-C and
      increased the HDL-C levels in serum. In addition, a significant (P < 0.01)
      decrease in LPO levels with increase in GSH content was observed in
      hyperhomocysteinemic rats treated with the aqueous extract of Embelia ribes. The
      results were comparable to those obtained with folic acid, a standard
      antihyperhomocysteinemic drug. CONCLUSION: The present results provide clear
      evidence that the aqueous extract of Embelia ribes treatment enhances the
      antioxidant defense against methionine-induced hyperhomocysteinemia,
      hyperlipidemia and oxidative stress in brain.

PMID- 20040949
TI  - Effect of methomyl on hepatic mixed function oxidases in rats.
AB  - OBJECTIVE: To study the effect of the methomyl on mixed function oxidase system
      in rats. MATERIALS AND METHODS: The effect of the methomyl on mixed function
      oxidase was studied using different dosages, durations and sex. Microsomes were
      isolated using the calcium precipitation method. The levels of cytochrome P(450)
      , and cytochrome b(5) were determined using extinction coefficient of 91 and 85
      mM(-1) respectively. The activities of drug metabolizing enzymes, hemoglobin
      content, liver function enzymes, and serum cholinesterase activity were assayed
      by using standard methods. RESULTS: Intraperitoneal administration of methomyl (4
      mg/kg body weight) showed significant decrease in the level of cytochrome P(450)
      , and the activities of aminopyrine N-demethylase and aniline hydroxylase on the
      third day of the treatment. Methomyl (4 mg/kg) treatment of old male rat and
      adult female rat also showed a decrease in the level of cytochrome P(450) , and
      aminopyrine N-demethylase activity. The serum samples from methomyl treated rats
      (male and female), when analyzed for alanine aminotransferase (SGPT) and
      aspartate aminotransferase (SGOT) as markers of the liver toxicity, showed
      significant increase in the activity. The activities of SGPT and SGOT were
      significantly higher in the treated rats (2 and 4 mg/kg) than in the control
      group. A significant decrease in the level of hemoglobin and serum cholinesterase
      activity was observed, when there was an increase in the dose level. A
      significant increase was observed in alkaline phosphatase activity at all dose
      levels. CONCLUSION: Methomyl influences mixed function oxidase and creates
      abnormality of liver functions in the rats. This effect depends on the dose and
      duration of methomyl.

PMID- 20040950
TI  - Sample purification procedure for confirmation of 3'-hydroxy stanozolol by gas
      chromatography/high resolution mass spectrometry.
AB  - OBJECTIVE: To improve the detection limit of 3'-hydroxy-stanozolol by using the
      double extraction procedure, specific for basic drugs. MATERIALS AND METHODS: The
      urine samples were spiked in four replicates with 3'-hydroxy-stanozolol at
      different concentrations of 1, 2, 5 and 10 ng/mL, processed by two different
      methods and injected into gas chromatography/high resolution mass spectrometry
      (GC-HRMS) instrument. The data was analyzed by comparing the recovery values and
      the ion match criterion of the two procedures. RESULTS: The results show that the
      recovery percentage and ion match criterion of 3'-hydroxy-stanozolol at lower
      concentrations has a significant improvement when Solid phase extraction was
      performed, instead of Liquid-liquid extraction in the second extraction
      procedure. CONCLUSION: The sample preparation procedure using Oasis-MCX
      cartridges allows confirmation of 3'-hydroxy-stanozolol at the minimum required
      performance limit (MRPL) decided by the World Anti Doping Agency. This procedure
      may be used for the confirmation of suspicious samples found in routine testing,
      as it efficiently fulfills the ion-matching criterion laid down by the World Anti
      Doping Agency.

PMID- 20040951
TI  - The effects of topical (gel) astemizole and terfenadine on wound healing.
AB  - OBJECTIVE: To develop topical gel preparations of astemizole and terfenadine and
      to investigate the actions of the gels on the healing of incision and excision
      wounds in male albino rats. MATERIALS AND METHODS: Gels containing 1% astemizole,
      with varying concentrations of carbopol 934 (polymer), were prepared. Similarly,
      1% terfenadine gels were made. The formulations were evaluated for release rate
      and stability. Incision and excision wounds were inflicted on male albino rats
      under ketamine anesthesia, taking aseptic precautions. The animals were divided
      into two groups. They were given a topical application of either astemizole or
      terfenadine gel, at a dose of 100 mg per wound, once daily, for 10 days in the
      case of incision wounds and till the time of complete closure in the case of
      excision wounds. On the 11(th) day, breaking strength of the incision wound was
      measured. In the excision wound model, wound closure rate, epithelization time,
      scar features and hydroxyproline content of scar tissue were studied from the day
      of wounding till the day of the scab falling off, with no residual raw area.
      RESULTS: Gels prepared using 0.8% carbopol 934 and 1% of drug in gel base were
      found to be stable. The gels of astemizole and terfenadine significantly (P <
      0.05) promoted the phases of healing such as collagenation (in incision wounds),
      wound contraction and epithelization (in excision wounds). CONCLUSION: The gels
      of astemizole and terfenadine might play an important role in wound management
      program.

PMID- 20040952
TI  - Evidences for the involvement of monoaminergic and GABAergic systems in
      antidepressant-like activity of garlic extract in mice.
AB  - OBJECTIVES: The present study was undertaken to investigate the effect of the
      ethanolic extract of Allium sativum L. (Family: Lilliaceae), commonly known as
      garlic, on depression in mice. MATERIALS AND METHODS: Ethanolic extract of garlic
      (25, 50 and 100 mg/kg) was administered orally for 14 successive days to young
      Swiss albino mice of either sex and antidepressant-like activity was evaluated
      employing tail suspension test (TST) and forced swim test (FST). The efficacy of
      the extract was compared with standard antidepressant drugs like fluoxetine and
      imipramine. The mechanism of action of the extract was investigated by co
      administration of prazosin (alpha1-adrenoceptor antagonist), sulpiride (selective
      D2-receptor antagonist), baclofen (GABA(B) agonist) and p-CPA (serotonin
      antagonist) separately with the extract and by studying the effect of the extract
      on brain MAO-A and MAO-B levels. RESULTS: Garlic extract (25, 50 and 100 mg/kg)
      significantly decreased immobility time in a dose-dependent manner in both TST
      and FST, indicating significant antidepressant-like activity. The efficacy of the
      extract was found to be comparable to fluoxetine (20 mg/kg p.o.) and imipramine
      (15 mg/kg p.o.) in both TST and FST. The extract did not show any significant
      effect on the locomotor activity of the mice. Prazosin, sulpiride, baclofen and p
      CPA significantly attenuated the extract-induced antidepressant-like effect in
      TST. Garlic extract (100 mg/kg) administered orally for 14 successive days
      significantly decreased brain MAO-A and MAO-B levels, as compared to the control
      group. CONCLUSION: Garlic extract showed significant antidepressant-like activity
      probably by inhibiting MAO-A and MAO-B levels and through interaction with
      adrenergic, dopaminergic, serotonergic and GABAergic systems.

PMID- 20040953
TI  - Intrathecal tramadol added to bupivacaine as spinal anesthetic increases
      analgesic effect of the spinal blockade after major gynecological surgeries.
AB  - The analgesic effect of the centrally acting opioid, tramadol, is well-known. It
      has been shown in clinical studies that using tramadol epidurally can provide
      longer duration of analgesia, without the common side effects of opioids. The
      study was undertaken to evaluate the duration of analgesia and/or pain free
      period produced by intrathecal tramadol added to bupivacaine in patients
      undergoing major gynecological surgery in a randomized double blind placebo
      controlled protocol. Fifty patients ASA I & II scheduled for Wardmayo's operation
      and Fothergill's operation were randomly allocated to two equal groups. Group A
      (n=25) received 3 ml of 0.5% hyperbaric bupivacaine (15 mg) with 0.2 ml of normal
      saline and Group B (n=25) received 3 ml 0.5% hyperbaric bupivacaine and 0.2 ml
      (20 mg) tramadol by intrathecal route at L3-4 inter space. Standard monitoring of
      the vital parameters was done during the study period. Levels of sensory block
      and sedation score were recorded every two minutes for the first 20 minutes, and
      then every ten minutes for the rest of the surgical procedure. Assessment of pain
      was done using Visual Analogue Scale (VAS). The study was concluded when the VAS
      was more than 40 mm, postoperatively. The patient was medicated and the time was
      recorded. Duration of analgesia or pain free period was estimated from the time
      of completion of spinal injection to administration of rescue analgesic or when
      the VAS score was greater than 40 mm. In Group B patients, the VAS score was
      significantly lower, as compared to Group A patients. The duration of analgesia
      was 210 +/- 10.12 min in Group A; whereas, in Group B, it was 380 +/- 11.82 min,
      which was found to be significant.

PMID- 20040954
TI  - Hypoglycemic effect of aqueous extract of Parthenium hysterophorus L. in normal
      and alloxan induced diabetic rats.
AB  - OBJECTIVES: To study the effects of Parthenium hysterophorus L. flower on serum
      glucose level in normal and alloxan induced diabetic rats. MATERIALS AND METHODS:
      Albino rats were divided into six groups of six animals each, three groups of
      normal animals receiving different treatments consisting of vehicle, aqueous
      extract of Parthenium hysterophorus L. flower (100 mg/kg) and the standard
      antidiabetic drug, glibenclamide (0.5 mg/kg). The same treatment was given to the
      other three groups comprising alloxan induced diabetic animals. Fasting blood
      glucose level was estimated using the glucose oxidase method in normal and
      alloxan induced diabetic rats, before and 2 h after the administration of drugs.
      RESULTS: Parthenium hysterophorus L. showed significant reduction in blood
      glucose level in the diabetic (P<0.01) rats. However, the reduction in blood
      glucose level with aqueous extract was less than with the standard drug
      glibenclamide. The extract showed less hypoglycemic effect in fasted normal rats,
      (P<0.05). CONCLUSION: The study reveals that the active fraction of Parthenium
      hysterophorus L. flower extract is very promising for developing standardized
      phytomedicine for diabetes mellitus.

PMID- 20040955
TI  - Ondansetron induced fatal ventricular tachycardia.
AB  - Ondansetron is a serotonin receptor antagonist used widely in the prophylaxis and
      treatment of postoperative nausea and vomiting (PONV) and vomiting associated
      with cancer chemotherapy. The common side effects of ondansetron are fever,
      malaise, diarrhoea, constipation, and allergic reactions. Extra-pyramidal
      reactions are rare and cardiovascular side effects are even rarer. Even though
      its clinical safety has been established in a large number of studies, its
      adverse effects have been reported and these include cardiovascular events like
      acute myocardial ischemia and arrhythmias in adults.([1]) Studies of its adverse
      effects in children are few. We report a rare adverse effect of ondansetron in a
      14-year-old girl, presenting as ventricular tachycardia.

PMID- 20040956
TI  - Early phase studies in India: Are we too early to explore?

PMID- 20040957
TI  - Partial nicotinic acetylcholine (alpha4beta2) agonists as promising new
      medications for smoking cessation.
AB  - OBJECTIVE: To review the pharmacology, clinical efficacy and safety of partial
      agonists of alpha4beta2 nicotinic acetylcholine receptor. DATA SOURCES: Primary
      literature and review articles were obtained via a PUBMED search (1988-August
      2006) using the key terms smoking cessation, partial agonist alpha4beta2
      nicotinic acetylcholine receptor, varenicline, cytisine and SSR591813. Additional
      studies and abstracts were identified from the bibliographies of reviewed
      literature. STUDY SELECTION AND DATA EXTRACTION: Studies and review articles
      related to varenicline, cytisine and the partial agonist alpha4beta2 nicotinic
      acetylcholine receptor were reviewed. DATA SYNTHESIS: Smoking is widely
      recognized as a serious health problem. Smoking cessation has major health
      benefits. According to the US Public Health Services, all patients attempting to
      quit smoking should be encouraged to use one or more effective pharmacotherapy.
      Currently, along with nicotine replacement therapy, bupropion, nortriptyline and
      clonidine, are the mainstay of pharmacotherapy. More than (3/4) of patients
      receiving treatment for smoking cessation return to smoking within the first
      year. Nicotine, through stimulating alpha4beta2 nAChR, releases dopamine in the
      reward pathway. Partial agonist of alpha4beta2 nAChR elicits moderate and
      sustained release of dopamine, which is countered during the cessation attempts;
      it simultaneously blocks the effects of nicotine by binding with alpha4beta2
      receptors during smoking. Recently, varenicline, a partial agonist at alpha4beta2
      nAChR, has been approved by the FDA (Food and Drug Administration) for smoking
      cessation. CONCLUSION: Partial agonist alpha4beta2 nAChR appears to be a
      promising target in smoking cessation. Varenicline of this group is approved for
      treatment of smoking cessation by the FDA in May 2006.

PMID- 20040958
TI  - Recent advances in pharmacotherapy of glaucoma.
AB  - Glaucoma is a slow progressive degeneration of the retinal ganglion cells (RGCs)
      and the optic nerve axons, leading to irreversible blindness if left undiagnosed
      and untreated. Although increased intraocular pressure is a major risk factor of
      glaucoma, other factors include increased glutamate levels, alterations in nitric
      oxide (NO) metabolism, vascular alterations and oxidative damage caused by
      reactive oxygen species. Glaucoma is the second leading cause of blindness
      globally, accounting for 12.3% of the total blindness. Glaucoma has been broadly
      classified as primary or secondary open-angle or angle-closure glaucoma. The
      primary goal in management of glaucoma is to prevent the risk factor, especially
      elevated intraocular pressure (IOP), using medications, laser therapy or
      conventional surgery. The first-line treatment of glaucoma usually begins with
      the use of a topical selective or nonselective blocker or a prostaglandin analog.
      Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase
      inhibitors. Cholinergic agonists are considered third-line treatment options.
      When a single therapy is not sufficient to lower the IOP, a combination therapy
      is indicated. To enhance the patient compliance, drug delivery systems like
      electronic devices, ocular inserts, tansdermal and mechanical drug delivery
      systems have been developed. Use of viscoelastic agents in ophthalmic
      formulations, emulsions and soluble ophthalmic drug inserts (SODI) enhance
      patience compliance and ocular drug delivery in patients in long-term glaucoma
      therapy. For patients who do not respond to antiglaucoma medications, laser
      trabeculoplasty and incisional surgery are recommended. Several nutrients and
      botanicals hold promise for the treatment of glaucoma, but most studies are
      preliminary, and larger, controlled studies are required. Future directions for
      the development of a novel therapy glaucoma may target glutamate inhibition, NMDA
      receptor blockade, exogenously applied neurotrophins, open channel blockers,
      antioxidants, protease inhibitors and gene therapy.

PMID- 20040959
TI  - Antiulcer activity of cod liver oil in rats.
AB  - OBJECTIVE: Cod liver oil is used widely as a dietary supplement. The present
      study was carried out to evaluate the effect of cod liver oil (0.5 g/kg, p.o. and
      1 g/kg, p.o.) on gastric and duodenal ulcers. MATERIALS AND METHODS: The study
      was carried out on different gastric ulcer models such as acetic acid induced
      chronic gastric ulcers, pylorus ligation, indomethacin induced ulcers, stress
      induced ulcers and ethanol induced ulcers. The duodenal ulcers were induced using
      cysteamine hydrochloride (HCl). Ranitidine (50 mg/kg p.o.) and misoprostol (100
      microg/kg, p.o.) were used as standard drugs. RESULTS: Both doses of cod liver
      oil showed gastric ulcer healing effect in acetic acid induced chronic gastric
      ulcers, produced gastric antisecretory effect in pylorus-ligated rats and also
      showed gastric cytoprotective effect in ethanol-induced and indomethacin-induced
      ulcer. Cod liver oil also produced a significant reduction in the development of
      stress induced gastric ulcers and cysteamine induced duodenal ulcer. The high
      dose of cod liver oil (1 g/kg, p.o.) was more effective compared to the low dose
      (0.5 g/kg, p.o.). CONCLUSION: Cod liver oil increases healing of gastric ulcers
      and prevents the development of experimentally induced gastric and duodenal
      ulcers in rats.

PMID- 20040961
TI  - Anti-dopaminergic effect of the methanolic extract of Morus alba L. leaves.
AB  - OBJECTIVE: To evaluate the effect of methanolic extract of Morus alba L. leaves
      on dopaminergic function. MATERIALS AND METHODS: The effect of the methanolic
      extract of Morus alba L. leaves was evaluated on haloperidol and metoclopramide
      induced catalepsy, foot shock-induced aggression, amphetamine-induced stereotyped
      behavior and phenobarbitone induced sleeping in mice. In each of these tests, the
      extract was administered in doses of 50, 100 and 200 mg/kg, i.p., 30 min before
      performing the test in mice. Further, the inhibitory effect of the extract on
      dopamine was studied using isolated rat vas deferens. RESULTS: The extract
      produced significant dose dependent potentiation of haloperidol (1 mg/kg, i.p.)
      and metoclopramide (20 mg/kg, i.p.) induced catalepsy in mice. The extract
      significantly reduced number of fights and increased latency to fights in foot
      shock-induced aggression; it also decreased amphetamine (1 mg/kg, i.p.) induced
      stereotyped behavior in a dose dependent manner. The sleeping time induced by
      phenobarbitone (50 mg/kg, i.p.) too was prolonged. The extract inhibited
      contractions produced by dopamine on isolated rat vas deferens. CONCLUSION: The
      results suggest that the methanolic extract of Morus alba L. possesses
      antidopaminergic activity. Further neurochemical investigation can explore the
      mechanism of action of the plant drug with respect to antidopaminergic functions
      and help to establish the plant as an antipsychotic agent.

PMID- 20040960
TI  - Protective effect of aqueous extract of Embelia ribes Burm fruits in middle
      cerebral artery occlusion-induced focal cerebral ischemia in rats.
AB  - OBJECTIVE: The present study was carried out to evaluate the neuroprotective
      effect of the aqueous extract of Embelia ribes, in focal ischemic brain.
      MATERIALS AND METHODS: Adult male Wistar albino rats were fed with the aqueous
      extract of Embelia ribes (100 and 200 mg/kg, p.o.) for 30 days. After 30 days of
      feeding, all the animals were anaesthetized with chloral hydrate (400 mg/kg,
      i.p.). The right middle cerebral artery was occluded with a 4-0 suture for 2 h.
      The suture was removed after 2 h, to allow reperfusion injury. The animals were
      used for grip strength measurement, biochemical estimation in serum and brain
      tissue (hippocampus and frontal cortex) and cerebral infarct size measurement.
      RESULTS: In the ischemic group, a significant (P < 0.01) alteration in the
      markers of oxidative damage (thiobarbituric acid reactive substances (TBARS);
      reduced glutathione (GSH); glutathione peroxidase (GPx); glutathione reductase
      (GR); and, glutathione-S-transferase (GST)) was observed in the hippocampus and
      frontal cortex, as compared to sham operated rats. We observed that the animals
      treated with the aqueous extract of Embelia ribes had a significant (P < 0.01)
      increase in the poststroke grip strength activity. Further, supplementation with
      aqueous extract of Embelia ribes reversed the levels/activities of the above
      mentioned biochemical parameters significantly (P< 0.01) and also resulted in
      decreased cerebral infarct area, as compared to the ischemic group. CONCLUSION:
      The results of our study, for the first time, provide clear evidence that aqueous
      extract of Embelia ribes pretreatment ameliorates cerebral ischemia/reperfusion
      injury and enhances the antioxidant defense against middle cerebral artery
      occlusion-induced cerebral infarction in rats; it exhibits neuroprotective
      property.

PMID- 20040962
TI  - Preliminary isolation and in vitro antiyeast activity of active fraction from
      crude extract of Gracilaria changii.
AB  - OBJECTIVE: To isolate the active fraction from crude extract of Gracilaria
      changii and to determine its in vitro antifungal activity. MATERIALS AND METHODS:
      The active fraction was isolated from the crude extract of G. changii by various
      purification procedures such as column chromatography, thin layer chromatography,
      bioauthograph etc. The in vitro antifungal activity (Candida albicans) of the
      active fraction (1.00, 0.50, and 0.25 mg/ml) was studied by disc diffusion method
      and the effect of the active fraction on the morphology of yeast was done by
      scanning electron microscope (SEM) studies. RESULTS: An active fraction with
      remarkable antifungal activity was separated from the crude extract. The active
      fraction was effective as a fungicide against C. albicans and showed a dose
      dependent antifungal activity. A Scanning Electron Microscope (SEM) study
      confirmed the fungicidal effect of G. changii active fraction on C. albicans, by
      changing the normal morphology of C. albicans. CONCLUSION: From G. changii crude
      extract, an active fraction with remarkable in vitro antifungal activity has been
      isolated.

PMID- 20040963
TI  - Antibiotic susceptibility patterns of Pseudomonas aeruginosa at a tertiary care
      hospital in Gujarat, India.
AB  - OBJECTIVES: The present study was undertaken to assess the antibiotic
      susceptibility patterns of Pseudomonas aeruginosa at a tertiary care hospital in
      Gujarat, India. Due to significant changes in microbial genetic ecology, as a
      result of indiscriminate use of anti-microbials, the spread of anti-microbial
      resistance is now a global problem. MATERIALS AND METHODS: Out of 276 culture
      positive samples, 56 samples of Pseudomonas aeruginosa were examined and 10
      different types of specimen were collected. Microbial sensitivity testing was
      done using disk diffusion test with Pseudomonas species NCTC 10662, as per CLSI
      guidelines. RESULTS: The highest number of Pseudomonas infections was found in
      urine, followed by pus and sputum. Pseudomonas species demonstrated marked
      resistance against monotherapy of penicillins, cephalosporins, fluoroquinolones,
      tetracyclines and macrolides. Only combination drugs like Ticarcillin +
      Clavulanic acid, Piperacillin + Tazobactum, Cefoperazone + Sulbactum, Cefotaxime
      + Sulbactum, Ceftriaxome + Sulbactum and monotherapy of amikacin showed higher
      sensitivity to Pseudomonas infections; however, the maximum sensitivity was shown
      by the Carbapenems. CONCLUSION: From the present study, we conclude that urinary
      tract infection was the most common hospital acquired infection. Also, co
      administration of beta -lactamase inhibitors markedly expanded the anti-microbial
      sensitivity of semi-synthetic penicillins and cephalosporins. The aminoglycoside
      group of antibiotics - amikacin - demonstrated maximum sensitivity against
      pseudomonas species. Therefore, use of amikacin should be restricted to severe
      nosocomial infections, in order to avoid rapid emergence of resistant strains.
      Periodic susceptibility testing should be carried out over a period of two to
      three years, to detect the resistance trends. Also, a rational strategy on the
      limited and prudent use of anti-Pseudomonal agents is urgently required.

PMID- 20040964
TI  - Effect of fresh Triticum aestivum grass juice on lipid profile of normal rats.
AB  - OBJECTIVE: To study the hypolipidemic activity of fresh grass juice of Triticum
      aestivum in normal rats. MATERIALS AND METHODS: Freshly prepared Triticum
      aestivum grass juice was administered to normal rats at the dose of 5 ml/kg and
      10 ml/kg orally once daily for 21 days. Blood samples were collected after 24
      hours of last administration and used for estimation of lipid profile. Fresh
      grass juice was also subjected to preliminary phytochemical screening. RESULTS:
      Fresh grass juice administration produced dose related significant (P < 0.05)
      reduction in total chloesterol, triglycerides, low density lipoprotein
      cholesterol and very low density lipoprotein-cholesterol levels in normal rats as
      compared to control. Preliminary phytochemical screening revealed presence of
      alkaloids, tannins, saponins and sterols in Triticum aestivum grass. CONCLUSION:
      The results of the present study lndicate hypolipidemic activity of fresh
      Triticum aestivum grass juice.

PMID- 20040965
TI  - Olanzapine induced tardive dystonia.
AB  - Advent of atypical antipsychotics was thought to be a major advancement in the
      psychopharmacology for schizophrenia. It was thought that these drugs would have
      low propensity to induce extrapyramidal symptoms including tardive movements.
      Olanzapine is a thienobenzodiazepine derivative, second generation (atypical)
      antipsychotic agent. Compared to typical antipsychotics, it has a greater
      affinity for serotonin 5-HT2A than dopamine D2 receptors, with preferential
      action at mesolimbic than nigrostriatal dopaminergic pathways. However, only few
      reports of olanzapine induced tardive dystonia (TD) are available in the
      literature. We wish to report another case of TD, in a male patient with
      schizophrenia, which developed after 15 months of treatment with olanzapine.

PMID- 20040966
TI  - Renal effects of environmental and occupational lead exposure.

PMID- 20040967
TI  - Neopterin: Biomarker of cell-mediated immunity and potent usage as biomarker in
      silicosis and other occupational diseases.
AB  - Neopterin is regarded as an early biomarker of the cellular immune response. This
      low molecular mass compound belongs to the class of pteridine and is a metabolite
      of guanosine triphosphate, which is produced by the activated macrophages and
      dendritic cells after stimulation with gamma-interferon. An international group
      acknowledges the fact that the levels of serum neopterin can be used as a marker
      of the effect of exposure to silica and other occupational diseases. The
      determination of neopterin is an innovative tool for monitoring diseases
      associated with the activation of cell-mediated immunity.

PMID- 20040968
TI  - Occupational health hazards in sewage and sanitary workers.
AB  - An estimated 1.2 million scavengers in the country are involved in the sanitation
      of our surroundings. The working conditions of these sanitary workers have
      remained virtually unchanged for over a century. Apart from the social atrocities
      that these workers face, they are exposed to certain health problems by virtue of
      their occupation. These health hazards include exposure to harmful gases such as
      methane and hydrogen sulfide, cardiovascular degeneration, musculoskeletal
      disorders like osteoarthritic changes and intervertebral disc herniation,
      infections like hepatitis, leptospirosis and helicobacter, skin problems,
      respiratory system problems and altered pulmonary function parameters. This can
      be prevented through engineering, medical and legislative measures. While the
      engineering measures will help in protecting against exposures, the medical
      measures will help in early detection of the effects of these exposures. This can
      be partly achieved by developing an effective occupational health service for
      this group of workers. Also, regular awareness programs should be conducted to
      impart education regarding safer work procedures and use of personal protective
      devices.

PMID- 20040969
TI  - Minor heavy metal: A review on occupational and environmental intoxication.
AB  - Heavy metal is widely used in industries and presents as a problematic
      environmental pollution. Some heavy metals, especially lead and mercury, are well
      described for their occupational and environmental intoxication whereas the other
      minor heavy metals are less concerned. In this article, the author will present
      the details of occupational and environmental minor heavy metal intoxication.
      This review focuses mainly on aluminum, tin, copper, manganese, chromium, cadmium
      and nickel.

PMID- 20040970
TI  - Safety in nuclear power plants in India.
AB  - Safety in nuclear power plants (NPPs) in India is a very important topic and it
      is necessary to dissipate correct information to all the readers and the public
      at large. In this article, I have briefly described how the safety in our NPPs is
      maintained. Safety is accorded overriding priority in all the activities. NPPs in
      India are not only safe but are also well regulated, have proper radiological
      protection of workers and the public, regular surveillance, dosimetry, approved
      standard operating and maintenance procedures, a well-defined waste management
      methodology, proper well documented and periodically rehearsed emergency
      preparedness and disaster management plans. The NPPs have occupational health
      policies covering periodic medical examinations, dosimetry and bioassay and are
      backed-up by fully equipped Personnel Decontamination Centers manned by doctors
      qualified in Occupational and Industrial Health. All the operating plants are ISO
      14001 and IS 18001 certified plants. The Nuclear Power Corporation of India
      Limited today has 17 operating plants and five plants under construction, and our
      scientists and engineers are fully geared to take up many more in order to meet
      the national requirements.

PMID- 20040971
TI  - Cost-benefit analysis of installing dust control devices in the agate industry,
      Khambhat (Gujarat).
AB  - It is well known that an exposure to crystalline silica gives rise to silicosis
      and silico-tuberculosis (TB). In the agate industry of Khambhat (Gujarat) not
      only workers but also people staying in the vicinity of the agate-grinding
      facilities are exposed to crystalline silica. To reduce their dust exposure, dust
      control devices were developed. There are approximately 500 grinding machines
      located in Khambhat. A cost-benefit analysis of installing dust control devices
      on all agate-grinding machines was carried out by adding all positive factors and
      benefits and subtracting the negatives and costs. It was concluded that by
      installing dust control devices not only could the prevalence of silicosis and TB
      be reduced but also, in the long run, there could be financial benefits.

PMID- 20040972
TI  - Occupational health risks among the workers employed in leather tanneries at
      Kanpur.
AB  - In a cross-sectional study, a random sample of 197 male workers drawn from
      different sections of 10 leather tanneries in Kanpur were selected for the
      assessment of health risks. A control group comprising of 117 male subjects
      belonging to a similar age group and socioeconomic strata, who never had any
      occupational exposure in the leather tanneries, were also examined for the
      comparison purpose. The findings revealed a significantly higher prevalence of
      morbidity among the exposed workers in contrast to that observed in the controls
      (40.1% vs. 19.6%). The respiratory diseases (16.7%) were mainly responsible for a
      higher morbidity among the exposed workers whereas the gastrointestinal tract
      problems were predominant in the control group. The urinary and blood samples
      collected from the exposed group showed significantly higher levels of chromium,
      thereby reflecting the body burden of Cr in the exposed workers as a result of a
      high concentration of environmental Cr at the work place.

PMID- 20040973
TI  - Retinal damages in turner workers of a factory exposed to intraocular foreign
      bodies.
AB  - Damages caused by an intraocular foreign body (IOFB) to the visual system, mainly
      the retina, mostly occur during certain occupational activities. Turners are
      among the laborers who are mostly exposed to IOFB. The aim of the present work is
      to survey the effect of an IOFB on the visual system, mainly the retina. Fifty
      laborers of a turner factory who were exposed to IOFB were selected.
      Electroretinography (ERG) was recorded in all the laborers. Beside these workers,
      50 laborers with no incidence of IOFB were also selected. They were also tested
      using ERG. The results obtained in the two groups were compared together to
      search for the possible changes in the two groups. The ERG patterns of the case
      groups were found to be changed in comparison to the control group. The changes
      were observed in the area under the b-wave of the ERG pattern in the early stage
      of damage and in the late stages, the latency and amplitude of the ERG b-wave
      were also affected. Finally, from the result of the present study, one can
      conclude that ERG is a suitable technique to search for the retinal changes in
      the laborers exposed to IOFB.

PMID- 20040974
TI  - Poisoning of workers working in small lead-based units.
AB  - BACKGROUND: No data are available with the labor departments among the workers of
      small-scale lead-based units with regard to lead poisoning. One hundred and
      ninety-five workers were investigated for lead exposure and three were found
      exceeding the limit of 80 mg/dL, which required a treatment for lead poisoning.
      AIM: To assess the exposure and health risk in workers working in small lead
      based units. SETTING AND DESIGN: Random sampling is selected from the cross
      sectional medical study. METHODS AND MATERIALS: Medical examination cum
      biochemical/hematological investigations along with blood lead estimation were
      carried out in these workers. STATISTICAL ANALYSIS: Epi-Info and SPSS 16.0 were
      used for statistical analysis. RESULTS AND CONCLUSION: Workers' blood lead levels
      were brought down from 114.4, 110.0 and 120.6 mg/dL with treatment of D
      penicillamine to 40 mg/dL. It may be concluded that lead poisoning is a
      preventable public health problem that particularly affects the industrial
      workers in small lead-based units.

PMID- 20040975
TI  - Emerging public health issues due to climate change.

PMID- 20040976
TI  - India needs a great sanitary awakening.

PMID- 20040977
TI  - Implementation of occupational health legislation at work place, issues and
      concerns.

PMID- 20040978
TI  - Occupational noise-induced hearing loss in India.
AB  - Noise is the insidious of all industrial pollutants, involving every industry and
      causing severe hearing loss in every country in the world. Exposure to excessive
      noise is the major avoidable cause of permanent hearing impairment. Worldwide,
      16% of the disabling hearing loss in adults is attributed to occupational noise,
      ranging from 7 to 21% in the various subregions. The estimated cost of noise to
      developed countries ranges from 0.2 to 2% of the gross domestic product (GDP).
      Noise-induced hearing loss (NIHL) is bilateral and symmetrical, usually affecting
      the higher frequencies (3k, 4k or 6k Hz) and then spreading to the lower
      frequencies (0.5k, 1k or 2k Hz). Other major health effects are lack of
      concentration, irritation, fatigue, headache, sleep disturbances, etc. The major
      industries responsible for excessive noise and exposing workers to hazardous
      levels of noise are textile, printing, saw mills, mining, etc. Hearing protectors
      should be used when engineering controls and work practices are not feasible for
      reducing noise exposure to safe levels. Earmuffs, ear plugs and ear canal caps
      are the main types of hearing protectors. In India, NIHL has been a compensable
      disease since 1948. It is only in 1996 that the first case got compensation.
      Awareness should be created among workers about the harmful effects of noise on
      hearing and other body systems by implementing compulsory education and training
      programs. There are very few published studies of NIHL in India. More extensive
      studies are needed to know the exact prevalence of NIHL among the various
      industries in India.

PMID- 20040979
TI  - Susceptibility and resistance in the genesis of asbestos-related mesothelioma.
AB  - Asbestos is the principal agent in the etiology of malignant mesothelioma.
      However, a small proportion of people exposed to asbestos develop mesothelioma.
      This suggests the role of host factors in the genesis of the tumor. A genetic
      susceptibility is suggested by the occurrence of more mesothelioma cases among
      blood-related members of a single family. Such an occurrence reached about 4% in
      a large mesothelioma series. In some studies, mesothelioma patients showed higher
      prevalences of additional malignancies when compared with controls. This
      indicates a particular vulnerability to cancer in people with mesothelioma. Not
      rarely, very old persons heavily exposed to asbestos remain free from asbestos
      related cancer, a fact indicating an absolute resistance to the oncogenic effects
      of asbestos. A relative resistance may be recognized in people severely exposed
      to asbestos who develop mesothelioma only after 60 years or more since the onset
      of the exposure. The long survivals, rarely observed among mesothelioma patients,
      have been attributed to a high efficiency of immune mechanisms. Mesotheliomas
      have been reported among people with severe immune impairment, such as acquired
      immunodeficiency syndrome patients or organ transplant recipients. The natural
      history of mesothelioma shows that a resistance to the oncogenic effects of
      asbestos does exist. Probably, such a resistance is due to the efficient immune
      mechanisms. To strengthen the defence mechanisms may represent a way for
      preventing mesothelioma among people exposed to asbestos.

PMID- 20040980
TI  - The sick building syndrome.
AB  - The sick building syndrome comprises of various nonspecific symptoms that occur
      in the occupants of a building. This feeling of ill health increases sickness
      absenteeism and causes a decrease in productivity of the workers. As this
      syndrome is increasingly becoming a major occupational hazard, the cause,
      management and prevention of this condition have been discussed in this article.

PMID- 20040981
TI  - E-waste hazard: The impending challenge.
AB  - Electronic waste or e-waste is one of the rapidly growing problems of the world.
      E-waste comprises of a multitude of components, some containing toxic substances
      that can have an adverse impact on human health and the environment if not
      handled properly. In India, e-waste management assumes greater significance not
      only due to the generation of its own e-waste but also because of the dumping of
      e-waste from developed countries. This is coupled with India's lack of
      appropriate infrastructure and procedures for its disposal and recycling. This
      review article provides a concise overview of India's current e-waste scenario,
      namely magnitude of the problem, environmental and health hazards, current
      disposal and recycling operations, existing legal framework, organizations
      working on this issue and recommendations for action.

PMID- 20040982
TI  - Investigation of respirable particulate matter pollutants on air-breathing zone
      workers in the Beam Rolling Mills Factory (Iran National Steel Industrial Group),
      Ahvaz, Iran.
AB  - Workers of iron and steel factories are exposed to a wide range of pollutants
      depending on the particular process, the materials involved, the effectiveness of
      monitoring and the control measures. Adverse effects are determined by the
      physical state and propensities of the pollutant involved, the intensity and
      duration of the exposure, the extent of pollutant accumulation in the body and
      the sensitivity of the individual to its effects. The main aim of this study is
      to assess the levels of the indoor respirable particulate matter (RPM) and to
      compare the health condition of exposed workers, with nonexposed employees group.
      Line 630 has only one furnace of 40 tons and line 650 has two furnaces of 20 and
      40 tons capacity due to which the mean of the RPM concentrations in the breathing
      zone was significantly different (P < 0.05) in line 650 but not in line 630 as
      compared with National Institute for Occupational Safety and Hygiene's (3
      mg/m(3)). The average of the RPM concentrations in production line 650 is higher
      than that of production line 630, with the 95% confidence interval in saw cabin
      station number 1 of production line 650.

PMID- 20040983
TI  - Solid-waste management in Jalandhar city and its impact on community health.
AB  - In this study, solid-waste management practices were evaluated in order to find
      out its link with occurrence of vector-borne disease. Strategies for solid-waste
      management were employed as practical model to solve the problems regarding
      pollution which is originated by solid-waste.

PMID- 20040984
TI  - The role of exhaust ventilation systems in reducing occupational exposure to
      organic solvents in a paint manufacturing factory.
AB  - This paper presents the successful design and implementation of several exhaust
      ventilation systems in a paint manufacturing factory. The ventilation systems
      were designed based on American Conference of Governmental Industrial Hygienists
      recommendations. The duct works, fans, and other parts were made and mounted by
      local manufacturers. The concentrations of toluene and xylene as the common
      solvents used in paint mixing factories were measured to evaluate the role of
      ventilation systems in controlling the organic solvents. Occupational exposure to
      toluene and xylene as the major pollutants was assessed with and without applying
      ventilation systems. For this purpose, samples were taken from breathing zone of
      exposed workers using personal samples. The samples were analyzed using
      Occupational Safety and Health Administration analytical method No.12. The
      samples were quantified using gas chromatography. The results showed that the
      ventilation systems successfully controlled toluene and xylene vapors in
      workplace, air well below the recommended threshold limit value of Iran (44.49
      and 97.73 ppm, respectively). It was also discovered that benzene concentration
      in workplace air was higher than its allowable concentrations. This could be from
      solvents impurities that require more investigations.

PMID- 20040985
TI  - Morbidity profile of steel pipe production workers.
AB  - OBJECTIVE: To study the different morbid conditions among steel pipe producing
      workers. METHODS: The present cross-sectional study has been carried out among
      the workers of one of the steel pipes and tubes manufacturing factory of Gujarat.
      Hundred workers from the four major departments of the steel pipe production
      plant, namely welding, pressing machine, X-ray welding and loading/transportation
      department were covered. The information regarding demographic, occupational,
      clinical characteristics and diagnosis were recorded on a pre-designed proforma.
      Statistical analysis included calculation of percentages and proportions and was
      carried out using the statistical software Epi Info Version 3.3.2. RESULTS: The
      mean age of the study subjects was found to be 38.7+/-7.1 years. The mean
      duration of exposure was found to be 9.0+/-3.4 years. Forty-four percent of the
      subjects had an upper respiratory tract infection, as evidenced by symptoms like
      dry cough, cough with rhinitis and cough with fever. Symptoms suggestive of
      allergic bronchitis were observed in 12% of the subjects while symptoms
      suggestive of heat stress such as prickly heat, dehydration, perspiration and
      pyrexia were observed in 13% of the subjects.

PMID- 20040986
TI  - Indian Association of Occupational Health denies industry influence.

PMID- 20040987
TI  - The Asian brown cloud.

PMID- 20040988
TI  - Global initiatives to prevent climate change.

PMID- 20040989
TI  - Counseling at work place: A proactive human resource initiative.

PMID- 20040990
TI  - Safety and occupational health: challenges and opportunities in emerging
      economies.

PMID- 20040991
TI  - Zinc toxicology following particulate inhalation.
AB  - The current mini-review describes the toxic effects of zinc inhalation
      principally in the workplace and associated complications with breathing and
      respiration. The International Classification of Functioning, Disability and
      Health Criteria were used to specifically select articles. Most of the commercial
      production of zinc involves the galvanizing of iron and the manufacture of brass.
      The recommended daily allowance for adults is 15 mg zinc/day. Metal fume fever
      associated with inhalation of fumes of ZnO is characterized by fatigue, chills,
      fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste and
      salivation. ZnCl(2) inhalation results in edema in the alveolar surface and the
      protein therein the lavage fluid is elevated. Particular pathological changes
      associated with zinc intoxication include: pale mucous membranes; jaundice;
      numerous Heinz bodies; and marked anemia. Adequate ambient air monitors for
      permissible exposure limits, excellent ventilation and extraction systems, and
      approved respirators are all important in providing adequate protection.

PMID- 20040992
TI  - An ergonomic study of women workers in a woolen textile factory for
      identification of health-related problems.
AB  - The observational cross-sectional study conducted on a sample of 100 women
      workers who volunteered, outlines their cardio-respiratory and musculo-skeletal
      profile before, during and at end of work. In addition, information on their
      health status in general was collected in advance.Contrary to expectation, there
      was no significant change in respiratory function. However, the musculo-skeletal
      problems were found to be abundantly present with pain in 91% of the subjects.
      Region-wise mapping of pain revealed that postural pain in low back was present
      in 47% while in neck was 19%. Scapular muscles on the right side were involved in
      stabilizing shoulder, which never went overhead. On the contrary, left shoulder
      was raised as high (>90 degrees) in spinning action, while pulling thread. This
      muscle work involved trapezius, deltoid and triceps action concentrically in
      lifting and while coming to starting position slowly, eccentrically. There was no
      pause since the wheel continued to spin the thread continuously, unless a worker
      opted to stop the work. Accordingly, left wrist and hand were in holding
      contraction while the right wrist and hand holding the handle were also in a
      fixed position with wrist in flexion with supinated forearm. Though the overall
      job was light as per peak HR, there was pain due to fatigue and grip strength
      weakened by around 10%, at the end of the day's work. In conclusion, pain and
      fatigue were found to be the main problems for women in the spinning section of
      the small-scale industry under this study. Women have to take up dual
      responsibility of a full-time job as well as the domestic work. It was considered
      that ergonomic factors such as provision of a backrest and frequent rest periods
      could remediate the musculo-skeletal symptoms.

PMID- 20040993
TI  - Ocular myasis and associated mucopurulent conjuctivitis acquired occupationally:
      A case study.
AB  - Ocular myasis and associated mucopurulent conjunctivitis in human eyes is a rare
      phenomenon. However, if the sheep bot fly abounds and poor hygienic environment
      prevails, the Oestrous ovis deposits its larvae in the conjunctival eye sac of
      human. The present paper reports a case study of ocular myasis among sheep farm
      workers caused by Oestrous ovis. The ocular myasis and the associated
      mucopurulent conjunctivitis are occupationally acquired in these cases. This
      study also suggests the treatment of patients and the recovery of the larvae.

PMID- 20040994
TI  - Noise exposure in oil mills.
AB  - CONTEXT: Noise of machines in various agro-based industries was found to be the
      major occupational hazard for the workers of industries. The predominant noise
      sources need to be identified and the causes of high noise need to be studied to
      undertake the appropriate measures to reduce the noise level in one of the major
      agro-based industries, oil mills. AIMS: To identify the predominant noise sources
      in the workrooms of oil mills. To study the causes of noise in oil mills. To
      measure the extent of noise exposure of oil mill workers. To examine the response
      of workers towards noise, so that appropriate measures can be undertaken to
      minimize the noise exposure. SETTINGS AND DESIGN: A noise survey was conducted in
      the three renowned oil mills of north-eastern region of India. MATERIALS AND
      METHODS: Information like output capacity, size of power source, maintenance
      condition of the machines and workroom configurations of the oil mills was
      collected by personal observations and enquiry with the owner of the mill. Using
      a Sound Level Meter (SLM) (Model-824, Larson and Davis, USA), equivalent SPL was
      measured at operator's ear level in the working zone of the workers near each
      machine of the mills. In order to study the variation of SPL in the workrooms of
      the oil mill throughout its operation, equivalent SPL was measured at two
      appropriate locations of working zone of the workers in each mill. For conducting
      the noise survey, the guidelines of Canadian Centre for Occupational Health and
      Safety (CCOHS) were followed. Grid points were marked on the floor of the
      workroom of the oil mill at a spacing of 1 m x 1 m. SPL at grid points were
      measured at about 1.5 m above the floor. The direction of the SLM was towards the
      nearby noisy source. To increase accuracy, two replications were taken at each
      grid point. All the data were recorded for 30 sec. At the end of the experiment,
      data were downloaded to a personal computer. With the help of utility software of
      Larson and Davis, USA, equivalent SPL and noise spectrum at each reading was
      obtained. Noise survey map of equivalent SPL was drawn for each oil mill by
      drawing contour lines on the sketch of the oil mill between the points of equal
      SPL. The floor area in the oil mill where SPL exceeded 85 dBA was identified from
      the noise survey map of each oil mill to determine the causes of high level of
      noise. Subjective assessment was done during the rest period of workers and it
      was assessed with personal interview with each worker separately. Demographic
      information, nature of work, working hours, rest period, experience of working in
      the mill, degree of noise annoyance, activity interference, and psychological and
      physiological effects of machine noise on the worker were asked during the
      interview. These details were noted in a structured form. STATISTICAL ANALYSIS
      USED: Nil. RESULTS: The noise survey conducted in three renowned oil mills of
      north-eastern region of India revealed that about 26% of the total workers were
      exposed to noise level of more than 85 dBA. Further, 10% to 30% floor areas of
      workrooms, where oil expellers are provided have the SPL of more than 85 dBA. The
      noise in the oil mills was dominated by low frequency noise. The predominant
      noise sources in the oil mills were seed cleaner and power transmission system to
      oil expellers. Poor maintenance of machines and use of bamboo stick to prevent
      the fall of belt from misaligned pulleys were the main reason of high noise.
      Noise emitted by the electric motor, table ghani and oil expellers in all the oil
      mills was well within 85 dBA. Subjective response indicated that about 63% of the
      total workers felt that noise interfered with their conversation. About 16% each
      were of the opinion that noise interfered in their work and harmed their hearing.
      About 5% of workers stated that the workroom noise gave them headaches.
      CONCLUSIONS: The workers engaged in the workrooms of the oil mills are exposed to
      high noise, which will have detrimental effect on their health. The poor
      maintenance of drive system was found to be the main reason for high noise level.

PMID- 20040995
TI  - Monitoring of plasma butyrylcholinesterase activity and hematological parameters
      in pesticide sprayers.
AB  - To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34
      male sprayers in the mango belt of Malihabad, a small town located 27 km from
      Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and
      complete blood count were assessed among sprayers after spraying pesticides and
      the findings obtained were compared with those determined in a reference group (n
      = 18). The most common symptoms observed were burning sensation in the eyes
      (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the
      exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased
      in workers. The results indicated significant decrease in the mean value of
      hemoglobin, hematocrit and platelets count; however, significantly higher count
      of leukocytes was also observed in the exposed group (sprayers) compared to that
      observed in the control group (P < 0.05). Monitoring of PBChE in pesticide
      sprayers could be useful to predict and prevent health hazards of OPs.

PMID- 20040996
TI  - A study on health status of women engaged in a home-based "Papad-making" industry
      in a slum area of Kolkata.
AB  - BACKGROUND: The 'papad-making' industries of India have provided ample
      opportunity of employment for the women workers of low socio-economic class
      although their problems are not much explored. In this study an attempt had been
      made for the same. AIMS: 1. To find out the health status of the women. 2. To
      find out the factors, in the working conditions, influencing their health status.
      3. To assess their felt needs. SETTINGS: A slum area of Kolkata. DESIGN: A cross
      sectional, descriptive type of observational study. METHODS AND MATERIALS: The
      slum was chosen by random sampling method. Following this, complete enumeration
      method was adopted. Data were collected by interview and clinical examination of
      the women engaged in this occupation with a predesigned and pretested schedule.
      STATISTICAL ANALYSIS: Proportions and Chi-square test. RESULTS: 77.5% were in the
      reproductive age group and none were below 14 years. Most of them belonged to
      poor socioeconomic status. Sixty per cent were in this occupation for more than
      10 years and they spent 5 hours for this work daily over and above their
      household job. Musculoskeletal problem was their commonest health problem.
      Pallor, angular stomatitis, pedal edema, chronic energy deficiency were found on
      examination. Personal hygienic measures taken were far from satisfactory. A focus
      group discussion revealed their health and family problems, dissatisfaction about
      their working conditions and wage. Other needs identified were home visits for
      their health care, free medicines and health education. CONCLUSION: Need exists
      for a participatory occupational health programme for this working population.

PMID- 20040997
TI  - Mental stress in the workers exposed to humidity in a cheese processing factory.
AB  - Certain inevitable physical factors in working environment can damage the workers
      in related fields. Sea sickness and white finger due to ship movement and
      vibration respectively are two examples in this regard. Humidity in working area
      can also bring discomfort of the workers in humid area. Cheese processing
      factories are such places where there is high humidity in the working
      space.Mental stress is a psychological complication which can arise due to some
      physical factors in certain occupational activities, therefore an attempt was
      made to have a search on mental stress in the laborers working in a cheese
      factory in Orumieheh, a city in north of Iran, with a cold climate throughout the
      year.For the purpose of the present study, a cheese processing factory with 100
      workers was selected. The workers were divided in to two groups. One group was
      exposed to high humidity and the other exposed to normal humidity level. A
      standard questionnaire was given to two groups to check the mental stress.The
      results obtained from both groups were compared.. The result showed severe mental
      stress in workers exposed to high humidity whereas moderate stress level in other
      workers.The conclusion of the present work is a proof of the adverse effect of
      humidity in working environments which reflect in mental stress in workers which
      will be discussed in detail in full paper.

PMID- 20040998
TI  - Environmental sanitation: An ignored issue in India.

PMID- 20040999
TI  - Awareness regarding global warming: Popular media like films need to contribute.

PMID- 20041001
TI  - A government under an asbestos roof.

PMID- 20041000
TI  - Industry influence on IAOH.

PMID- 20041002
TI  - Debate on industry influence on OH organizations/T.K. Joshi's tantrums!

PMID- 20041003
TI  - Editor's response.

PMID- 20041004
TI  - Progressive Multifocal Leukoencephalopathy in HIV-Infected Children: A Case
      Report and Literature Review.
AB  - We report a case of a perinatally HIV-infected patient aged 9 years, who
      presented with right-sided hemiplegia. His initial CD4 T-cell was of 0.21% (4
      cells/muL) and plasma HIV RNA virus of 185 976 copies/mL (log 5.27). Plasma and
      CSF samples were subsequently positive for JCV. Twelve days after the initiation
      of highly active antiretroviral therapy (HAART), the MRI showed progressive white
      matter lesions with asymmetrical deep and subcortical white matter lesions over
      the left frontotemporoparietal region and the right frontal lobe. Immune
      Reconstitution Inflammatory Syndrome (IRIS) was suspected, and the patient was
      treated with methylprednisolone. His clinical symptoms worsened and despite
      therapy the patient deteriorated.

PMID- 20041005
TI  - Comparative Study of 5-Day and 10-Day Cefditoren Pivoxil Treatments for Recurrent
      Group A beta-Hemolytic Streptococcus pharyngitis in Children.
AB  - Efficacy of short-course therapy with cephalosporins for treatment of group A
      beta-hemolytic streptococcus (GABHS) pharyngitis is still controversial. Subjects
      were 226 children with a history of at least one episode of GABHS pharyngitis.
      Recurrence within the follow-up period (3 weeks after initiation of therapy)
      occurred in 7 of the 77 children in the 5-day treatment group and in 1 of the 149
      children in the 10-day treatment group; the incidence of recurrence being
      significantly higher in the 5-day treatment group. Bacteriologic treatment
      failure (GABHS isolation without overt pharyngitis) at follow-up culture was
      observed in 7 of the 77 children in the 5-day treatment group and 17 of the 149
      children in the 10-day treatment group. There was no statistical difference
      between the two groups. A 5-day course of oral cephalosporins is not always
      recommended for treatment of GABHS pharyngitis in children who have repeated
      episodes of pharyngitis.

PMID- 20041006
TI  - Mechanical Complication with Broviac Repair Kit in a 4-Year-Old Boy with MEN 2a.
AB  - Background. Mechanical complications in the use of indwelling central venous
      catheters (CVCs) such as the Broviac catheter (BC) include kinking, occlusion,
      dislocation or leaking. We report on a mechanical complication after using a
      repair kit for the BC. Method. A 4-year old boy, suffering from multiple
      endocrine neoplasia type 2a (MEN 2a), intestinal aganglionosis (Hirschsprung's
      disease), and short bowel syndrome, required a BC for home parenteral nutrition.
      Result. Due to recurrent leakage of the BC, 5 subsequent repairs were necessary
      within seven months. During one repair a metallic tube belonging to the repair
      kit was found to have migrated proximally to the skin entrance level within the
      BC and requiring surgical removal. Conclusion. To our knowledge, this is the
      first report focusing on such a serious complication using a BC and its repair
      kit. The proximal migration of this metallic tube constitutes a distinct
      theoretical risk of endothoracic foreign body embolization.

PMID- 20041007
TI  - Prevalence of Underweight, Stunting, and Wasting among Children Infected with
      Human Immunodeficiency Virus in South India.
AB  - Background. Growth failure is a common feature of children with human
      immunodeficiency virus (HIV) infection. Malnutrition increases mortality and may
      impair the response to antiretroviral treatment. Objective. Our objective was to
      describe the prevalence of stunting, underweight, and wasting in HIV-infected
      children in south India and to assess the utility of these parameters in
      predicting immune status. Methodology. In this cross-sectional study,
      anthropometric measurements and CD4 counts were performed on 231 HIV-infected
      children. Z scores for height for age, weight for age, and weight for height were
      correlated with CD4 cell counts and receiver operating characteristic curves
      plotted. Results. Prevalence of underweight was 63%, stunting 58%, and wasting
      16%, respectively. 33-45% of children were moderately or severely malnourished
      even at CD4 >25%; sensitivity and specificity of stunting or underweight to
      predict HIV disease severity was low. Conclusions. Undernutrition and stunting
      are common among HIV-infected children at all stages of the disease in India.
      Early and aggressive nutritional intervention is required, if long-term outcomes
      are to be improved.

PMID- 20041008
TI  - Intramural ganglion structures in esophageal atresia: a morphologic and
      immunohistochemical study.
AB  - Introduction and Aim. Disorders of esophageal motility causing dysphagia and
      gastroesophageal reflux are frequent in survivors to esophageal atresia (EA) and
      distal tracheoesophageal fistula (TEF). The aim of the present study was to
      investigate the histologic and immunohistochemical features in both esophageal
      atretic segments to further understand the nature of the motor disorders observed
      in these patients. Material and Methods. Esophageal specimens from 12 newborns
      with EA/TEF and 5 newborns dead of unrelated causes were examined. The specimens
      were fixed in 5% buffered formalin, included in paraffin and cut in 5 micron
      sections that were stained with hematoxilin and eosin (H and E), and
      immunohistochemical stainings for Actin, S-100 protein, Neurofilament, Neuron
      Specific-Enolase, Chromogranin A and Peripherin were evaluated under the
      microscope. Results. In controls, the distribution of the neural elements was
      rather homogenous at both levels of the esophagus. In contrast, the atretic
      segments showed quantitative and qualitative differences between them with
      sparser nervous tissue in the distal one in comparison with the proximal one and
      with controls. Conclusions. These results further support the assumption that
      histomorphological alterations of the muscular and nervous elements within the
      esophageal wall might contribute to esophageal dysmotility in patients surviving
      neonatal operations for EA/TEF.

PMID- 20041009
TI  - Characterization of acute lymphoblastic leukemia subtypes in moroccan children.
AB  - We present the incidence and the immunologic characteristics of acute
      lymphoblastic leukemia (ALL) subsets in Moroccan children. We studied 279
      unselected patients below the age of 18 years with newly diagnosed ALL. Cases
      were classified according to immunophenotype: 216 (77.42%) precursor B-cell
      phenotype (pB-cell), mature B-cell in 4 (1.43%), and T-cell in 59 (21.15%) cases.
      The subclassification using the CD10 antibody revealed 197 cases pB-ALL CD10+
      (91.2%) and 9 cases T-ALL CD10+ (19.2%). The age distribution showed a peak in
      incidence between 3 and 5 years among the pB-cell ALLs subtype. There was a
      significantly higher frequency of males in the T-ALL subset (M/F ratio: 2.93 : 1)
      and more females in the T-ALL CD10+ subset when compared with the T-ALL CD10-
      subset. All tested pB-cell-lineage ALLs expressed CD19, CD79a, and surface CD22,
      terminal deoxynucleotidyl transferase (TdT) was detectable in 89.9% of cases, and
      cells in 74.1% of cases express CD34. All tested T-lineage ALL cells have surface
      CD7 and cytoplasmic CD3 (cCD3) antigens, CD5 was found in 98.2% cases, and 70.5%
      express TdT. CD1a, surface CD3 (sCD3), and CD4 are detected in more than 80% of
      cases; this frequency is higher than the 45% generally observed. Myeloid antigens
      occur more frequently and were expressed in 124 (57.4%) of pB-cell-ALL cases and
      20 (33.9%) of T-cell ALL cases. Our results show that the distribution of ALLs in
      Moroccan children is similar with the general distribution pattern in developed
      countries except for the high frequency of T-ALL phenotype. The phenotypic
      profiles of our patients are close to those reported in literature for B-lineage
      ALLs; for the T-cell ALL subgroup, the blast cells express more CD1a, surface
      CD3, and CD4 while expressing less TdT. The high frequency of CD1a expression
      resulted in an excess of the common thymocyte subtype.

PMID- 20041010
TI  - Child skeletal fluorosis from indoor burning of coal in southwestern China.
AB  - OBJECTIVES: We assess the prevalence and pathogenic stage of skeletal fluorosis
      among children and adolescents residing in a severe coal-burning endemic
      fluorosis area of southwest China. METHODS: We used a cross-sectional design. A
      total of 1,616 students aged between 7 and 16 years in Zhijin County, Guizhou,
      China in late 2004 were selected via a cluster sampling of all 9-year compulsory
      education schools to complete the study questionnaire. Any student lived in a
      household that burned coal, used an open-burning stove, or baked foodstuffs over
      a coal stove was deemed high-risk for skeletal fluorosis. About 23% (370) of
      students (188 boys, 182 girls) were identified as high-risk and further examined
      by X-ray. RESULTS: One-third of the 370 high-risk participants were diagnosed
      with skeletal fluorosis. Overall prevalence of child skeletal fluorosis due to
      indoor burning of coal was 7.5%. Children aged 12-16 years were significantly
      more likely to be diagnosed with skeletal fluorosis than children aged 7-11 years
      (OR = 1.84, 95% CI: 1.17-2.90; P = .0082). Four types of skeletal fluorosis were
      identified: constrictive (60.7%), raritas (15.6%), mixed (16.4%), and soft
      (7.4%). Most diagnosed cases (91%) were mild or moderate in severity. In
      addition, about 97% of 370 high-risk children were identified with dental
      fluorosis. Dental fluorosis was highly correlated with skeletal fluorosis in this
      study. CONCLUSIONS: Skeletal fluorosis among children may contribute to poor
      health and reduced productivity when they reach adulthood. Further efforts to
      reduce fluoride exposure among children in southwestern of China where coal is
      burned indoors are desperately needed.

PMID- 20041011
TI  - Be careful, mom and doc: hepatotoxicity associated with prescribed medications in
      young infants.
AB  - Accidental poisonings in young infants are relatively uncommon, and the careless
      caregiver is usually the culprit. We report two cases of hepatotoxicity due to
      prescribed medications. An infant was given 15 mL instead of 1.5 mL of
      paracetamol by his mother because she omitted the decimal point on the label of
      the drug bottle. The infant became symptomatic, and liver enzyme and clotting
      profile were abnormal, necessitating treatment with N-acetyl cysteine. Another
      infant was prescribed oral ketoconazole for thrush, resulting in elevation of
      liver enzymes. The serum alanine aminotransferase levels were transiently
      elevated but returned to normal, and both infants recovered uneventfully. This
      report serves to alert the doctor to avoid using decimal points in drug labeling
      and to avoid prescribing excessive amount of drug for trivial acute illness.
      Thrush in infancy is common and usually treated with oral nystatin. Other oral
      antifungals such as ketoconazole may be associated with liver derangement and
      should be avoided in infants.

PMID- 20041012
TI  - Total pesticide exposure calculation among vegetable farmers in Benguet,
      Philippines.
AB  - This was a cross-sectional study that investigated pesticide exposure and its
      risk factors targeting vegetable farmers selected through cluster sampling. The
      sampling size calculated with P = .05 was 211 vegetable farmers and 37 farms. The
      mean usage of pesticide was 21.35 liters. Risk factors included damaged backpack
      sprayer (34.7%), spills on hands (31.8%), and spraying against the wind (58%).
      The top 3 pesticides used were pyrethroid (46.4%), organophosphates (24.2%), and
      carbamates (21.3%). Those who were exposed to fungicides and insecticides also
      had higher total pesticide exposure. Furthermore, a farmer who was a pesticide
      applicator, mixer, loader, and who had not been given instructions through
      training was at risk of having higher pesticide exposure. The most prevalent
      symptoms were headache (64.1%), muscle pain (61.1%), cough (45.5%), weakness
      (42.4%), eye pain (39.9%), chest pain (37.4%), and eye redness (33.8%). The data
      can be used for the formulation of an integrated program on safety and health in
      the vegetable industry.

PMID- 20041013
TI  - Maternal psychological problems associated with neonatal intensive care
      admission.
AB  - Background. Mothers of infants admitted to a neonatal intensive care unit (NICU)
      are believed to have heightened distress. The purpose of this paper was to
      determine depression and anxiety symptoms and attachment style in NICU mothers.
      Methods. The NICU group consisted of mothers whose infants were admitted to the
      NICU and the control group consisted of mothers of healthy term infants. The
      psychosocial assessments were done at the first month. Results. The mean
      Edinburgh Postpartum Depression (EPDS) score of NICU mothers was significantly
      higher than that of the control group mothers (9.6 +/- 5.6 versus 7.3 +/- 4.9, P
      = .005). NICU mothers who had high EPDS (>/=13) scores had significantly higher
      anxiety scores and insecure attachment style in comparison to the subgroup of
      NICU mothers who had low EPDS scores. Conclusion. Mothers of NICU babies had
      higher EPDS scores. Mothers who had higher EPDS scores had higher anxiety scores
      as well. These NICU mothers should receive appropriate counseling during the
      hospitalization of their babies.

PMID- 20041014
TI  - OccIDEAS: retrospective occupational exposure assessment in community-based
      studies made easier.
AB  - Assessing occupational exposure in retrospective community-based case-control
      studies is difficult as measured exposure data are very seldom available. The
      expert assessment method is considered the most accurate way to attribute
      exposure but it is a time consuming and expensive process and may be seen as
      subjective, nonreproducible, and nontransparent. In this paper, we describe these
      problems and outline our solutions as operationalized in a web-based software
      application (OccIDEAS). The novel aspects of OccIDEAS are combining all steps in
      the assessment into one software package; enmeshing the process of assessment
      into the development of questionnaires; selecting the exposure(s) of interest;
      specifying rules for exposure assignment; allowing manual or automatic
      assessments; ensuring that circumstances in which exposure is possible for an
      individual are highlighted for review; providing reports to ensure consistency of
      assessment. Development of this application has the potential to make high
      quality occupational assessment more efficient and accessible for epidemiological
      studies.

PMID- 20041015
TI  - Phadiatop infant in the diagnosis of atopy in children with allergy-like
      symptoms.
AB  - Background and Objective. Allergy-like symptoms such as wheezing and eczema are
      common in young children and an early diagnosis is important to initiate correct
      management. The objective of this study was to evaluate the diagnostic
      performance of Phadiatop Infant, an in vitro test for determination of early
      sensitisation to food and inhalant allergens. Patients and Methods. The study was
      conducted, retrospectively, using frozen sera from 122 children (median age 2.7
      years) admitted to the hospital with suspected allergic symptoms. The doctor's
      diagnosis atopic/nonatopic was based on routinely used procedures such as
      clinical evaluation, SPT, total and allergen-specific IgE antibodies. The
      performance of Phadiatop Infant was evaluated in a blinded manner against this
      diagnosis. Results. Eighty-four of the 86 children classified as atopic showed a
      positive Phadiatop Infant test. Thirty-six were classified as nonatopic, 32 of
      who had a negative test. With a prevalence of atopy of 70% in this population,
      this gives a sensitivity of 98%, a specificity of 89%, and a positive and
      negative predictive value of 95% and 94%, respectively. Conclusion. The results
      from the present study suggest that Phadiatop Infant could be recommended as a
      complement to the clinical information in the differential diagnosis on IgE
      mediated disease in young children with allergy-like symptoms.

PMID- 20041016
TI  - Toxicity of xanthene food dyes by inhibition of human drug-metabolizing enzymes
      in a noncompetitive manner.
AB  - The synthetic food dyes studied were rose bengal (RB), phroxine (PL), amaranth,
      erythrosine B (ET), allura red, new coccine, acid red (AR), tartrazine, sunset
      yellow FCF, brilliant blue FCF, and indigo carmine. First, data confirmed that
      these dyes were not substrates for CYP2A6, UGT1A6, and UGT2B7. ET inhibited
      UGT1A6 (glucuronidation of p-nitrophenol) and UGT2B7 (glucuronidation of
      androsterone). We showed the inhibitory effect of xanthene dye on human UGT1A6
      activity. Basic ET, PL, and RB in those food dyes strongly inhibited UGT1A6
      activity, with IC(50) values = 0.05, 0.04, and 0.015 mM, respectively. Meanwhile,
      AR of an acidic xanthene food dye showed no inhibition. Next, we studied the
      inhibition of CYP3A4 of a major phase I drug-metabolizing enzyme and P
      glycoprotein of a major transporter by synthetic food dyes. Human CYP3A4 and P
      glycoprotein were also inhibited by basic xanthene food dyes. The IC(50) values
      of these dyes to inhibit CYP3A4 and P-glycoprotein were the same as the
      inhibition level of UGT1A6 by three halogenated xanthene food dyes (ET, PL, and
      RB) described above, except AR, like the results with UGT1A6 and UGT2B7. We also
      confirmed the noninhibition of CYP3A4 and P-gp by other synthetic food dyes. Part
      of this inhibition depended upon the reaction of (1)O(2) originating on xanthene
      dyes by light irradiation, because inhibition was prevented by (1)O(2) quenchers.
      We studied the influence of superoxide dismutase and catalase on this inhibition
      by dyes and we found prevention of inhibition by superoxide dismutase but not
      catalase. This result suggests that superoxide anions, originating on dyes by
      light irradiation, must attack drug-metabolizing enzymes. It is possible that red
      cosmetics containing phloxine, erythrosine, or rose bengal react with proteins on
      skin under lighting and may lead to rough skin.

PMID- 20041017
TI  - Pediatric migraine.
AB  - Migraine is the most common cause of acute recurrent headaches in children. The
      pathophysiological concepts have evolved from a purely vascular etiology to a
      neuroinflammatory process. Clinical evaluation is the mainstay of diagnosis and
      should also include family history. Investigations help to rule out secondary
      causes. The role of new drugs in treatment of migraine is discussed and trials
      are quoted from literature. Indications for starting prophylaxis should be
      evaluated based on frequency of attacks and influence on quality of life. For
      management of acute attacks of migraine both acetaminophen and ibuprofen are
      recommended for use in children. Many drugs like antiepileptic drugs (AED),
      calcium channel blockers, and antidepressants have been used for prophylaxis of
      migraine in children. The data for use of newer drugs for migraine in children is
      limited, though AEDs are emerging a popular choice. Biofeedback and other
      nonmedicinal therapies are being used with promising results.

PMID- 20041018
TI  - Subjective risk assessment and perception in the Greek and English bakery
      industries.
AB  - Several factors influencing risk perception in the area of occupational health
      and safety are known, but there is still lack of a full understanding of the ways
      in which people characterize risk. This study aimed to provide an insight of
      employee risk assessment and perception in the bakery industry. 87 British and 64
      Greek employees in two comparable bakery companies were asked to estimate and
      evaluate hazards at their workplace. The participants' judgments of 12 hazards
      according to 7 risk aspects-were collected and analyzed. Subjective assessment on
      important occupational hazards included handling heavy loads, repetitiveness,
      high temperatures, high rate of work, stressful deadlines, and noise. Although
      limited in the population involved, our findings revealed strong cross-national
      differences in employee risk perception of specific groups of hazards in the
      bakery industry. Additional interviews revealed evidence that Greek employees'
      risk perception depends mostly on work experience while British employees were
      aware of risks due to company health and safety policy, recognizing that safety
      is the responsibility of both the management and the worker. Cross-national
      (cultural) factors that influence workforce risk perception and attitudes towards
      safety have to be taken into account by technical experts and policy makers in
      the designing of prevention strategies and risk communication.

PMID- 20041019
TI  - Association between Infant Feeding and Early Postpartum Infant Body Composition:
      A Pilot Prospective Study.
AB  - Research studies have produced conflicting results of the impact of breastfeeding
      on overweight/obesity. This study evaluated the impact of infant feeding on
      infant body composition. There were two groups of mother-infant pairs (exclusive
      breastfeeding [EBF; n = 27] and mixed feeding [MF; n = 13]) in this study. At
      baseline, participants were similar in their demographic characteristics except
      prepregnancy weight, where MF mothers tended to be heavier than their EBF
      counterparts (67.3 kg versus 59.9 kg; P = .034). Infant birth weight was slightly
      higher among the MF group than their EBF counterparts (3.5 kg versus 3.4 kg),
      although the differences were not statistically significant. At 3 months
      postpartum, mean infant FMI (4.1 kg/m(2) versus 3.8 kg/m(2)) and percent body fat
      (24.4% versus 23.1%) were slightly higher among EBF infants than MF infants. In
      terms of growth velocity, EBF infants gained weight faster than their MF
      counterparts, although the differences were not statistically significant. The
      findings from this study suggest that EBF may promote faster weight gain and
      increase in both fat mass index (FMI) and percent body fat in the early
      postpartum period in addition to the numerous health benefits enjoyed by the
      infant and the mother who exclusively breastfeeds her newborn.

PMID- 20041020
TI  - Legionella antibodies in a Danish hospital staff with known occupational
      exposure.
AB  - Although legionnaires' disease frequently is acquired in health care
      institutions, little is known about the occupational risk of Legionella infection
      among health care workers. The aim of the present cross-sectional study was to
      analyse antibody levels among exposed hospital workers and to determine the
      correlation between antibodies to Legionella and self-reported symptoms. The
      study included 258 hospital employees and a reference group of 708 healthy blood
      donors. Hospital workers had a higher prevalence of Legionella antibody titres
      (>/=1 : 128) than blood donors (odds ratio 3.4; 95% CI 2.4-4.8). Antibody levels
      were not higher among staff members at risk of frequent aerosol exposure than
      among less exposed employees. There was no consistent association between a
      history of influenza-like symptom complex and the presence of antibodies. The
      results indicate that hospital workers have a higher risk of Legionella
      infections than the general population. However, since no excess morbidity was
      associated with seropositivity, most Legionella infections may be asymptomatic.

PMID- 20041021
TI  - Antibacterial activity of some lactic acid bacteria isolated from an Algerian
      dairy product.
AB  - In the present study, the antibacterial effect of 20 lactic acid bacteria
      isolates from a traditional cheese was investigated. 6 isolates showed
      antibacterial effect against Gram positive bacteria. Streptococcus thermophilus
      T2 strain showed the wide inhibitory spectrum against the Gram positive bacteria.
      Growth and bacteriocin production profiles showed that the maximal bacteriocin
      production, by S. thermophilus T2 cells, was measured by the end of the late-log
      phase (90 AU ml(-1)) with a bacteriocine production rate of 9.3 (AU ml(-1)) h(
      1). In addition, our findings showed that the bacteriocin, produced by S.
      thermophilus T2, was stable over a wide pH range (4-8); this indicates that such
      bacteriocin may be useful in acidic as well as nonacidic food. This preliminarily
      work shows the potential application of autochthonous lactic acid bacteria to
      improve safety of traditional fermented food.

PMID- 20041022
TI  - Role of socioeconomic indicators on development of obesity from a life course
      perspective.
AB  - AIMS: Development of obesity is modified by several factors, including
      socioeconomic ones. We studied the importance of socioeconomic indicators on the
      development of obesity from a life course perspective. METHODS: 2003 people born
      1934-1944 in Helsinki, Finland, participated in clinical examinations in 2001
      2004. Obesity was defined as body mass index (BMI) >30 kg/m(2). RESULTS:
      Prevalence of obesity was 22.3% in men and 27.2% in women. Lower educational
      attainment and lower adult social class were associated with higher BMI in both
      men (P = .03 and P < .01) and women (P < .001 and P = .01). Childhood social
      class was inversely associated with BMI only in men (P < .001); lower household
      income was associated with higher BMI in women only (P < .001). Those men
      belonging to the lowest childhood social class had higher risk of being obese
      than those of the highest childhood social class (OR 1.8 (95% CI: 1.0-3.1)).
      Household income was the strongest predictor of obesity among women. CONCLUSION:
      Overweight and obesity are inversely associated with socioeconomic status. Men
      seem to be more susceptible to adverse childhood socioeconomic circumstances than
      women, while adult socioeconomic indicators were more strongly associated with
      obesity in women.

PMID- 20041023
TI  - The contribution of home, neighbourhood and school environmental factors in
      explaining physical activity among adolescents.
AB  - The present study aimed at investigating the influence of home, neighbourhood and
      school environmental factors on adolescents' engagement in self-reported
      extracurricular physical activity and leisure time sports and on MVPA objectively
      measured by accelerometers. Environmental factors were assessed using
      questionnaires. Gender specific hierarchical regression analyses were conducted,
      with demographic variables entered in the first block, and environmental,
      psychosocial factors and interactions terms entered in the second block.
      Participation in extracurricular activities at school was positively related to
      the number of organized activities and the provision of supervision. Perceived
      accessibility of neighborhood facilities was not related to engagement in leisure
      time sports, whereas the availability of sedentary and physical activity
      equipment was. Findings were generally supportive of ecological theories stating
      that behaviors are influenced by personal and environmental factors that are
      constantly interacting.

PMID- 20041024
TI  - Effect of physical activity and obesity on type 2 diabetes in a middle-aged
      population.
AB  - BACKGROUND: The physical activity has been associated with a reduced risk of type
      2 diabetes. The aim of this study was to examine the effect of physical
      activities such as occupational, household and daily lifestyle activities and
      obesity on the prevalence of type 2 diabetes in middle-aged population. METHODS:
      All people (n = 2053), aged 45-64 years were selected for this study from the
      large sample of population-based cross-sectional data collected in the 1990-1994
      by National Health Survey of Pakistan. The participants completed in-person
      interviews at baseline; the overall response rate was 92.6%. The Cox proportional
      hazards model was used to estimate the risk of developing the type 2 diabetes.
      RESULTS: Stair climbing was found to be inversely associated with the risk of
      diabetes and cycling was also associated with a reduced risk of type 2 diabetes
      (RR = 0.82; 95% CI 0.68-1.00, P = .048). The relationship between physical
      activity and reduced risk of diabetes adjusted for age and body mass index was
      statistically significant only in women (P < .01). CONCLUSIONS: This study
      provides an incentive that physical activity in leisure-time exercise or daily
      activity reduces the risk of type 2 diabetes in a high-risk population.

PMID- 20041025
TI  - Assessment of noise and associated health impacts at selected secondary schools
      in Ibadan, Nigeria.
AB  - BACKGROUND: Most schools in Ibadan, Nigeria, are located near major roads (mobile
      line sources). We conducted an initial assessment of noise levels and adverse
      noise-related health and learning effects. METHODS: For this descriptive, cross
      sectional study, four schools were selected randomly from eight participating in
      overall project. We administered 200 questionnaires, 50 per school, assessing
      health and learning-related outcomes. Noise levels (A-weighted decibels, dBA)
      were measured with calibrated sound level meters. Traffic density was assessed
      for school with the highest measured dBA. Observational checklists assessed noise
      control parameters and building physical attributes. RESULTS: Short-term, cross
      sectional school-day noise levels ranged 68.3-84.7 dBA. Over 60% of respondents
      reported that vehicular traffic was major source of noise, and over 70%
      complained being disturbed by noise. Three schools reported tiredness, and one
      school lack of concentration, as the most prevalent noise-related health
      problems. CONCLUSION: Secondary school occupants in Ibadan, Nigeria were
      potentially affected by exposure to noise from mobile line sources.

PMID- 20041026
TI  - Arthralgia and osteolytic lesions associated with traumatic pancreatitis in a 10
      year-old girl.
AB  - A case of traumatic pancreatitis with subsequent joint pain and osteolytic
      lesions is presented. A 10-year-old girl was admitted to our hospital with
      abdominal pain caused by blunt epigastric injury. She was diagnosed with
      traumatic pancreatitis, and multiple pancreatic pseudocysts subsequently
      developed. Two weeks after admission, she complained of joint pain, and MR
      revealed osteolytic lesions of both knee joints. On the 58th day, endoscopic
      transgastric pseudocyst drainage was performed. Joint pain and osteolytic lesions
      resolved rapidly, in parallel with the decrease in serum amylase level and
      pseudocyst size.

PMID- 20041028
TI  - "Deconstructing" scientific research: a practical and scalable pedagogical tool
      to provide evidence-based science instruction.

PMID- 20041029
TI  - Maternal infection with Trypanosoma cruzi and congenital Chagas disease induce a
      trend to a type 1 polarization of infant immune responses to vaccines.
AB  - BACKGROUND: We previously showed that newborns congenitally infected with
      Trypanosoma cruzi (M+B+) display a strong type 1 parasite-specific T cell immune
      response, whereas uninfected newborns from T. cruzi-infected mothers (M+B-) are
      prone to produce higher levels of proinflammatory cytokines than control neonates
      (M-B-). The purpose of the present study was to determine if such fetal/neonatal
      immunological environments could alter the response to standard vaccines
      administered in early life. METHODOLOGY: Infants (6-7 months old) living in
      Bolivia, an area highly endemic for T. cruzi infection, and having received
      Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus
      vaccines, were enrolled into the M+B+, M+B-, M-B- groups mentioned above. The
      production of IFN-gamma and IL-13, as markers of Th1 and Th2 responses
      respectively, by peripherical blood mononuclear cells stimulated with tuberculin
      purified protein derivative of Mycobacterium tuberculosis (PPD) or the vaccinal
      antigens HBs, diphtheria toxoid (DT) or tetanus toxoid (TT), as well as
      circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in
      infants. Cellular responses to the superantigen SEB were also monitored in M+B+,
      M+B-, M-B-infants and newborns. PRINCIPAL FINDINGS: M+B+ infants developed a
      stronger IFN-gamma response to hepatitis B, diphtheria and tetanus vaccines than
      did M+B- and M-B- groups. They also displayed an enhanced antibody production to
      HBsAg. This was associated with a type 1-biased immune environment at birth,
      since cells of M+B+ newborns produced higher IFN-gamma levels in response to SEB.
      M+B- infants produced more IFN-gamma in response to PPD than the other groups. IL
      13 production remained low and similar in all the three groups, whatever the
      subject's ages or vaccine status. CONCLUSION: These results show that: i) both
      maternal infection with T. cruzi and congenital Chagas disease do not interfere
      with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the
      neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi
      infection in early life is not limited to the development of parasite-specific
      immune responses, but also tends to favour type 1 immune responses to vaccinal
      antigens.

PMID- 20041030
TI  - Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a
      LysR-type transcription regulator.
AB  - Phenotypic variation within an isogenic bacterial population is thought to ensure
      the survival of a subset of cells in adverse conditions. The opportunistic
      pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including
      antibiotic resistance, biofilm formation, and the production of CupA fimbriae.
      Here we describe a previously unidentified bistable switch in P. aeruginosa. This
      switch controls the expression of a diverse set of genes, including aprA, which
      encodes the secreted virulence factor alkaline protease. We present evidence that
      bistable expression of PA2432, herein named bexR (bistable expression regulator),
      which encodes a LysR-type transcription regulator, controls this switch. In
      particular, using DNA microarrays, quantitative RT-PCR analysis, chromatin
      immunoprecipitation, and reporter gene fusions, we identify genes directly under
      the control of BexR and show that these genes are bistably expressed.
      Furthermore, we show that bexR is itself bistably expressed and positively
      autoregulated. Finally, using single-cell analyses of a GFP reporter fusion, we
      present evidence that positive autoregulation of bexR is necessary for bistable
      expression of the BexR regulon. Our findings suggest that a positive feedback
      loop involving a LysR-type transcription regulator serves as the basis for an
      epigenetic switch that controls virulence gene expression in P. aeruginosa.

PMID- 20041033
TI  - Plasma levels of transforming growth factor-beta1 reflect left ventricular
      remodeling in aortic stenosis.
AB  - BACKGROUND: TGF-beta1 is involved in cardiac remodeling through an auto/paracrine
      mechanism. The contribution of TGF-beta1 from plasmatic source to pressure
      overload myocardial remodeling has not been analyzed. We investigated, in
      patients with valvular aortic stenosis (AS), and in mice subjected to transverse
      aortic arch constriction (TAC), whether plasma TGF-beta1 relates with myocardial
      remodeling, reflected by LV transcriptional adaptations of genes linked to
      myocardial hypertrophy and fibrosis, and by heart morphology and function.
      METHODOLOGY/PRINCIPAL FINDINGS: The subjects of the study were: 39 patients
      operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham
      operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-beta1
      was determined by ELISA. Under pressure overload, TGF-beta1 plasma levels were
      significantly increased both in AS patients and TAC mice. In AS patients, plasma
      TGF-beta1 correlated directly with aortic transvalvular gradients and LV mass
      surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF
      beta1 correlated positively with the myocardial expression of genes encoding
      extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin
      light chain-2, beta-myosin heavy chain) remodelling targets of TGF-beta1, in TAC
      mice and in AS patients. CONCLUSIONS/SIGNIFICANCE: A circulating TGF-beta1
      mediated mechanism is involved, in both mice and humans, in the excessive
      deposition of ECM elements and hypertrophic growth of cardiomyocytes under
      pressure overload. The possible value of plasma TGF-beta1 as a marker reflecting
      preoperative myocardial remodeling status in AS patients deserves further
      analysis in larger patient cohorts.

PMID- 20041034
TI  - Discovery of novel proteasome inhibitors using a high-content cell-based
      screening system.
AB  - The regulated degradation of damaged or misfolded proteins, as well as down
      regulation of key signaling proteins, within eukaryotic and bacterial cells is
      catalyzed primarily by large, ATP-dependent multimeric proteolytic complexes,
      termed proteasomes. Inhibition of proteasomal activity affects a wide variety of
      physiological and pathological processes, and was found to be particularly
      effective for cancer therapy. We report here on the development of a novel high
      throughput assay for proteasome inhibition using a unique, highly sensitive live
      cell screening, based on the cytoplasm-to-nucleus translocation of a fluorescent
      proteasome inhibition reporter (PIR) protein, consisting of nuclear localization
      signal-deficient p53 derivative. We further show here that mdm2, a key negative
      regulator of p53 plays a key role in the accumulation of PIR in the nucleus upon
      proteasome inhibition. Using this assay, we have screened the NCI Diversity Set
      library, containing 1,992 low molecular weight synthetic compounds, and
      identified four proteasome inhibitors. The special features of the current
      screen, compared to those of other approaches are discussed.

PMID- 20041035
TI  - ADAPTIVE DATA ANALYSIS OF COMPLEX FLUCTUATIONS IN PHYSIOLOGIC TIME SERIES.
AB  - We introduce a generic framework of dynamical complexity to understand and
      quantify fluctuations of physiologic time series. In particular, we discuss the
      importance of applying adaptive data analysis techniques, such as the empirical
      mode decomposition algorithm, to address the challenges of nonlinearity and
      nonstationarity that are typically exhibited in biological fluctuations.

PMID- 20041036
TI  - HIV Prevention Research: Are We Meeting the Needs of African American Men Who
      Have Sex With Men?
AB  - Two decades of HIV prevention efforts with men who have sex with men (MSM) have
      not eliminated the risk of new HIV infections in this vulnerable population.
      Indeed, current incidence rates in African American MSM are similar to those
      usually only seen in developing countries. A review of the existing literature
      suggests that the prevention research agenda for Black MSM could benefit from
      reframing conceptualization of risk as a function of individual properties to a
      broad consideration of social and interpersonal determinants. Studies that
      investigate dyadic and social-level influences on African American MSM's
      relationships are needed. This includes research explicating the diversity
      existing within the categorizations of Black MSM with respect to perceived
      identity (gay, bisexual, "men on the down low," "homo thugz"), constructions of
      masculinity, sexual scripts, sources of social support, and perceived norms and
      expectations. Recommendations are proposed for a research agenda focusing on
      linkages between interpersonal and social-structural determinants of HIV risk.

PMID- 20041037
TI  - Seasonal population dynamics and behaviour of insects in models of vector-borne
      pathogens.

PMID- 20041038
TI  - Analysis of coupled model uncertainties in source-to-dose modeling of human
      exposures to ambient air pollution: A PM(2.5) case study.
AB  - Quantitative assessment of human exposures and health effects due to air
      pollution involve detailed characterization of impacts of air quality on exposure
      and dose. A key challenge is to integrate these three components on a consistent
      spatial and temporal basis taking into account linkages and feedbacks. The
      current state-of-practice for such assessments is to exercise emission,
      meteorology, air quality, exposure, and dose models separately, and to link them
      together by using the output of one model as input to the subsequent downstream
      model. Quantification of variability and uncertainty has been an important topic
      in the exposure assessment community for a number of years. Variability refers to
      differences in the value of a quantity (e.g., exposure) over time, space, or
      among individuals. Uncertainty refers to lack of knowledge regarding the true
      value of a quantity. An emerging challenge is how to quantify variability and
      uncertainty in integrated assessments over the source-to-dose continuum by
      considering contributions from individual as well as linked components. For a
      case study of fine particulate matter (PM(2.5)) in North Carolina during July
      2002, we characterize variability and uncertainty associated with each of the
      individual concentration, exposure and dose models that are linked, and use a
      conceptual framework to quantify and evaluate the implications of coupled model
      uncertainties. We find that the resulting overall uncertainties due to combined
      effects of both variability and uncertainty are smaller (usually by a factor of 3
      4) than the crudely multiplied model-specific overall uncertainty ratios. Future
      research will need to examine the impact of potential dependencies among the
      model components by conducting a truly coupled modeling analysis.

PMID- 20041039
TI  - Knowledge and Use of Low Vision Services Among Persons with Age-related Macular
      Degeneration.

PMID- 20041040
TI  - 1000 Genomes on the Road to Personalized Medicine.

PMID- 20041041
TI  - Development of an Agrobacterium-mediated transformation protocol for the tree
      legume Leucaena leucocephala using immature zygotic embryos.
AB  - The tree-legume Leucaena leucocephala (leucaena) is used as a perennial fodder
      because of its fast-growing foliage, which is high in protein content. The use of
      leucaena as a fodder is however restricted due to the presence of the toxin
      mimosine. Improvements in the nutritional contents as well as other agronomic
      traits of leucaena can be accomplished through genetic transformation. The
      objective of this research was to develop a transformation protocol for leucaena
      using phosphinothricin resistance as the plant selectable marker. Explants
      obtained from immature zygotic embryos infected with the Agrobacterium
      tumefaciens strain C58C1 containing the binary plasmid pCAMBIA3201 produced four
      putative transformed leucaena plants. Transformation was con- firmed by PCR, RT
      PCR, Southern blot, Western analyses, GUS-specific enzyme activity and herbicide
      leaf spraying assay. A transformation efficiency of 2% was established using this
      protocol.

PMID- 20041043
TI  - Optimal Defaults and Active Decisions.
AB  - Defaults often have a large influence on consumer decisions. We identify an
      overlooked but practical alternative to defaults: requiring individuals to make
      an explicit choice for themselves. We study such "active decisions" in the
      context of 401(k) saving. We find that compelling new hires to make active
      decisions about 401(k) enrollment raises the initial fraction that enroll by 28
      percentage points relative to a standard opt-in enrollment procedure, producing a
      savings distribution three months after hire that would take 30 months to achieve
      under standard enrollment. We also present a model of 401(k) enrollment and
      derive conditions under which the optimal enrollment regime is automatic
      enrollment (i.e., default enrollment), standard enrollment (i.e., default non
      enrollment), or active decisions (i.e., no default and compulsory choice). Active
      decisions are optimal when consumers have a strong propensity to procrastinate
      and savings preferences are highly heterogeneous. Financial illiteracy, however,
      favors default enrollment over active decision enrollment.

PMID- 20041044
TI  - Quality of high-energy X-ray radiotherapy beams: Issues of adequacy of routine
      experimental verification.

PMID- 20041045
TI  - Dosimetric evaluation of rectum and bladder using image-based CT planning and
      orthogonal radiographs with ICRU 38 recommendations in intracavitary
      brachytherapy.
AB  - The purpose is to compare CT-based dosimetry with International Commission on
      Radiation Units and Measurements (ICRU 38) bladder and rectum reference points in
      patients of carcinoma of uterine cervix treated with intracavitary brachytherapy
      (ICA). Twenty-two consecutive patients were evaluated. Orthogonal radiographs and
      CT images were acquired and transferred to PLATO planning system. Bladder and
      rectal reference points were identified according to ICRU 38 recommendations.
      Dosimetry was carried out based on Manchester system. Patient treatment was done
      using (192)Iridium high dose rate (HDR) remote after-loading machine based on the
      conventional radiograph-based dosimetry. ICRU rectal and bladder point doses from
      the radiograph plans were compared with D(2), dose received by 2 cm(3) of the
      organ receiving maximum dose from CT plan. V(2), volume of organ receiving dose
      more than the ICRU reference point, was evaluated. The mean (+/-standard
      deviation) volume of rectum and bladder was 60 (+/-28) cm(3) and 138 (+/-41)
      cm(3) respectively. The mean reference volume in radiograph and CT plan was 105
      (+/-7) cm(3) and 107 (+/-7) cm(3) respectively. It was found that 6 (+/-4) cm(3)
      of rectum and 16 (+/-10) cm(3) of bladder received dose more than the
      prescription dose. V(2) of rectum and bladder was 7 (+/-1.7) cm(3) and 20.8 (+/
      6) cm(3) respectively. Mean D(2) of rectum and bladder was found to be 1.11 (+/
      0.2) and 1.56 (+/-0.6) times the mean ICRU reference points respectively. This
      dosimteric study suggests that comparison of orthogonal X-ray-based and CT-based
      HDR ICA planning is feasible. ICRU rectal point dose correlates well with maximum
      rectal dose, while ICRU bladder point underestimates the maximum bladder dose.

PMID- 20041046
TI  - A new approach to position reconstruction in TOFPET.
AB  - Monte Carlo Simulation (MCS) is a state-of-the-art technique in designing
      sophisticated apparatus for various applications in science and technology. We
      adopted MCS based on GEANT (GEometry ANd Tracking) in order to design a simple
      time-of-flight positron emission tomography (TOFPET). In MCS studies, a new
      method of position reconstruction of positron-electron annihilation points has
      been developed so far. Simulation results show that this technique may not be
      useful for small animal imaging camera but might be practicable in diagnostic
      TOFPET camera. Specific issue of this simulation technique is discussed.

PMID- 20041042
TI  - Translational studies of alcoholism: bridging the gap.
AB  - Human studies are necessary to identify and classify the brain systems
      predisposing individuals to develop alcohol use disorders and those modified by
      alcohol, while animal models of alcoholism are essential for a mechanistic
      understanding of how chronic voluntary alcohol consumption becomes compulsive,
      how brain systems become damaged, and how damage resolves. Our current knowledge
      of the neuroscience of alcohol dependence has evolved from the interchange of
      information gathered from both human alcoholics and animal models of alcoholism.
      Together, studies in humans and animal models have provided support for the
      involvement of specific brain structures over the course of alcohol addiction,
      including the prefrontal cortex, basal ganglia, cerebellum, amygdala,
      hippocampus, and the hypothalamic-pituitary-adrenal axis.

PMID- 20041047
TI  - Dosimetry and treatment planning of Occu-Prosta I-125 seeds for intraocular
      lesions.
AB  - Intraocular malignant lesions are frequently encountered in clinical practice.
      Plaque brachytherapy represents an effective means of treatment for intraocular
      lesions. Recently Radiopharmaceutical Division, BARC, Mumbai, has indigenously
      fabricated reasonable-cost I-125 sources. Here we are presenting the preliminary
      experience of dosimetry of sources, configuration of treatment planning system
      (TPS) and quality assurance (QA) for eye plaque therapy with Occu-Prosta I-125
      seeds, treated in our hospital, for a patient with ocular lesions. I-125 seeds
      were calibrated using well-type chamber. BrachyVision TPS was configured with
      Monte Carlo computed radial dose functions and anisotropy functions for I-125
      sources. Dose calculated by TPS at different points in central axis and off axis
      was compared with manually calculated dose. Eye plaque was fabricated of 17 karat
      pure gold, locally. The seeds were arranged in an outer ring near the edge of the
      plaque and in concentric rings throughout the plaque. The sources were manually
      digitized on the TPS, and dose distribution was calculated in three dimensions.
      Measured activity using cross-calibrated well-type chamber was within +/-10% of
      the activity specified by the supplier. Difference in TPS-calculated dose and
      manually calculated dose was within 5%. Treatment time calculated by TPS was in
      concordance with published data for similar plaque arrangement.

PMID- 20041048
TI  - Application of small-angle X-ray scattering for differentiation among breast
      tumors.
AB  - Small-angle X-ray scattering (SAXS) is an X-ray diffraction-based technique where
      a narrow collimated beam of X-rays is focused onto a sample and the scattered X
      rays recorded by a detector. The pattern of the scattered X-rays carries
      information on the molecular structure of the material. As breast cancer is the
      most widespread cancer in women and differentiation among its tumors is
      important, this project compared the results of coherent X-ray scattering
      measurements obtained from benign and malignant breast tissues. The energy
      dispersive method with a setup including X-ray tube, primary collimator, sample
      holder, secondary collimator and high-purity germanium (HpGe) detector was used.
      One hundred thirty-one breast-tissue samples, including normal, fibrocystic
      changes and carcinoma, were studied at the 6 degrees scattering angle.
      Diffraction profiles (corrected scattered intensity versus momentum transfer) of
      normal, fibrocystic changes and carcinoma were obtained. These profiles showed a
      few peak positions for adipose (1.15 +/- 0.06 nm(-1)), mixed normal (1.15 +/-
      0.06 nm(-1) and 1.4 +/- 0.04 nm(-1)), fibrocystic changes (1.46 +/- 0.05 nm(-1)
      and 1.74 +/- 0.04 nm(-1)) and carcinoma (1.55 +/- 0.04 nm(-1), 1.73 +/- 0.06 nm(
      1), 1.85 +/- 0.05 nm(-1)). We were able to differentiate between normal,
      fibrocystic changes (benign) and carcinoma (malignant) breast tissues by SAXS.
      However, we were unable to differentiate between different types of carcinoma.

PMID- 20041050
TI  - Pediatric radiography entrance doses for some routine procedures in three
      hospitals within eastern Nigeria.
AB  - A survey of the entrance surface doses in the routine radiography of children in
      eastern Nigeria has been carried out in three hospitals, using thermoluminescence
      detectors. Chest, abdomen, lumbar spine, skull and pelvis were covered in this
      study. Findings reveal that doses are higher than the recommended reference
      values elsewhere, as well as values reported for Sudan. The mean percentage
      difference in entrance doses for chest radiography for this study and an earlier
      one carried out for three hospitals in the west of Nigeria is about 44.7%. The
      high doses are traceable to a lack of standardization in procedure, resulting in
      use of low tube voltages and high currents for examination, as well as the status
      of facilities in the area. Recommendations are made for immediate corrective
      measures to lower the doses.

PMID- 20041049
TI  - Solid water phantom heat conduction: Heating and cooling rates.
AB  - Solid water is often the phantom material of choice for dosimetry procedures in
      radiotherapy high-energy X-ray and electron beam radiation calibration and
      quality assurance. This note investigates variation in heat conduction that can
      occur for a common commercially available solid water stack phantom when a
      temperature differential occurs between the phantom and ambient temperature.
      These variations in temperature can then affect radiation measurements and thus
      the accuracy of radiation dosimetry. In this manuscript, we aim to investigate
      the variations in temperature which can occur in radiation measurement
      incorporated (RMI) solid water phantoms, their thermal properties and the effects
      on radiation dosimetry which can occur because of temperature differentials.
      Results have shown that the rate of temperature change at a phantom center is a
      complex function but appears relatively proportional to the surface area of the
      phantom in normal clinical usage. It is also dependent on the thermal
      conductivity of any material in contact with the phantom; and the nature of the
      phantom construction, i.e., the number and thickness of slices within the
      phantom. A thermal time constant of approximately 20 min was measured for a 2-cm
      solid water phantom slice when located on a steel workbench in comparison to 60
      min when located on a wooden workbench (linac couch insert). It is found that for
      larger solid water stack phantoms, a transient (within 1 degrees C) thermal
      equilibrium exists at the center for up to 2 h, before the temperature begins to
      change. This is assumed to be due to the insulating properties of multiple slices
      within the stack, whereby very small air spaces are introduced inhibiting the
      heat conduction through the phantom material. It is therefore recommended that
      the solid water/phantom material is kept within the treatment room for closest
      thermal accuracy conditions or at least placed within the room approximately 10 h
      before dosimetry measurements. If these options are not available, a standard
      linear interpolation method for calculation of temperature should be used to
      minimize uncertainty of temperature measurements.

PMID- 20041051
TI  - Risk factors and surgical treatment for symptomatic adjacent segment degeneration
      after lumbar spine fusion.
AB  - OBJECTIVE: The present study analyzed the risk factors, prevalence and clinical
      results following revision surgery for adjacent segment degeneration (ASD) in
      patients who had undergone lumbar fusion. METHODS: Over an 8-year period, we
      performed posterior lumbar fusion in 81 patients. Patients were followed a
      minimum of 2 years (mean 5.5 years). During that time, 9 patients required
      revision surgery due to ASD development. Four patients underwent autogenous
      posterolateral arthrodesis and extended transpedicle screw fixation, 4 patients
      underwent decompressive laminectomy and interspinous device implantation, and 1
      patient underwent simple decompression. RESULTS: Of the 9 of patients with
      clinical ASD, 33.3% (3 of 9) of patients did not have radiographic ASD on plain
      radiographs. Following revision surgery, the clinical results were excellent or
      good in 8 patients (88.9%). Age > 50 years at primary surgery was a significant
      risk factor for ASD development, while number of fusion levels, initial diagnosis
      and type of fusion were not. CONCLUSION: The incidence of ASD development after
      lumbar surgery was 11.1% (9 of 81) in this study. Age greater than 50 was the
      statistically significant risk factor for ASD development. Similar successful
      clinical outcomes were observed after extended fusion with wide decompression or
      after interspinous device implantation. Given the latter procedure is less
      invasive, the findings suggest it may be considered a treatment alternative in
      selected cases but it needs further study.

PMID- 20041052
TI  - The BioFlex System as a Dynamic Stabilization Device : Does It Preserve Lumbar
      Motion?
AB  - OBJECTIVE: This study examines whether functional motion is present at one or
      more years after Bioflex System placement. BioFlex System is a flexible rod
      system which has been used to preserve motion at the area of implantation. There
      has not been a scientific study showing how much motion is preserved after
      implantation. METHODS: A total of 12 consecutive patients underwent posterior
      dynamic stabilization using the BioFlex System. Six patients were treated using a
      L3-4-5 construct and other six patients using a L4-5-S1 construct. Follow-up
      ranged from 12 to 33 months and standing neutral lateral, extension, flexion and
      posteroanterior (PA) radiographs were obtained at 3, 6, 9, and 12 months and at
      more than 12 months postoperatively. Range of motion (ROM), whole lumbar
      lordosis, and ROMs of motion segments from L2 to S1 were determined. RESULTS:
      Patients with a L3-4-5 construct demonstrated a decrease in mean ROM for whole
      lumbar decreased from 40.08 to 30.77. Mean ROM for L3-4 (6.12 to 2.20) and L4-5
      (6.55 to 1.67) also decreased after one year. Patients with a L4-5-S1 construct
      demonstrated L4-5 (8.75 to 2.70) and L5-S1 (9.97 to 3.25) decrease of mean ROM at
      one year postoperatively. Lumbar lordosis was preserved at both L3-4-5 and L4-5
      S1 constructs. Clinical results showed significant improvements in both study
      groups. CONCLUSION: The present study provides preliminary information regarding
      the BioFlex motion preservation system. We conclude that the BioFlex System
      preserves functional motion to some degree at instrumented levels. However,
      although total lumbar lordosis was preserved, ROMs at implantation segments were
      lower than preoperative values.

PMID- 20041053
TI  - The change of adjacent segment and sagittal balance after thoracolumbar spine
      surgery.
AB  - OBJECTIVE: To characterize perioperative biomechanical changes after thoracic
      spine surgery. METHODS: Fifty-eight patients underwent spinal instrumented
      fusions and simple laminectomies on the thoracolumbar spine from April 2003 to
      October 2008. Patients were allocated to three groups; namely, the laminectomy
      without fusion group (group I, n = 17), the thoracolumbar fusion group (group II,
      n = 27), and the thoracic spine fusion group (group III, n = 14). Sagittal (ADS)
      and coronal (ADC) angles for adjacent segments were measured from two disc spaces
      above lesions at the upper margins, to two disc spaces below lesions at the lower
      margins. Sagittal (TLS) and coronal (TLC) angles of the thoracolumbar junction
      were measured from the lower margin of the 11th thoracic vertebra body to the
      upper margin of the 2nd lumbar vertebra body on plane radiographs. Adjacent
      segment disc heights and disc signal changes were determined using simple spinal
      examinations and by magnetic resonance imaging. Clinical outcome indices were
      determined using a visual analog scale. RESULTS: The three groups demonstrated
      statistically significant differences in terms of angle changes by ANOVA (p <
      0.05). All angles in group I showed significantly smaller angles changes than in
      groups II and III by Turkey's multiple comparison analysis. Coronal Cobb's angles
      of the thoracolumbar spine (TLC) were not significantly different in the three
      groups. CONCLUSION: Postoperative sagittal balance is expected to change in the
      adjacent and thoracolumbar areas after thoracic spine fusion. However, its
      prevalence seems to be higher when the thoracolumbar spine is included in
      instrumented fusion.

PMID- 20041054
TI  - 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  - OBJECTIVE: We estimated the number of Korean adults with back pain and evaluated
      population-based associated factors of back pain from a representative sample
      data from the Fourth Korea National Health and Nutrition Examination Survey.
      METHODS: The number of Korean adults who experienced back pain (experienced
      patients), those who experienced back pain lasting for three or more months
      during the past year (chronic patients), and those who were currently suffering
      from back pain (current patients) were estimated by analyzing the data from the
      fourth Korea National Health and Nutrition Examination Survey conducted in 2007
      using surveyfreq procedure of the SAS statistical package. Population-based odds
      ratios for being experienced, chronic, and current patient according to
      demographic (age and gender), socioeconomic (education and occupation), and
      lifestyle factors (smoking, drinking, and exercise) were estimated using
      surveylogistic procedure. RESULTS: It was estimated that there were 5,554,256
      (proportion, 15.4%; 95% CI, 4,809,466 - 6,299,046) experienced patients,
      2,060,829 (5.7%; 1,557,413-2,564,246) chronic patients, and 3,084,188 (8.5%;
      2,600,197 - 3,568,179) current patients among 36,107,225 Korean adults aged 20-89
      years in 2007. Each of explanatory variables was significantly associated with at
      least one of the response variables for back pain. CONCLUSION: Based on our study
      results, further efforts to investigate epidemiology of back pain, to evaluate
      associated factors, and to improve treatment outcomes are needed.

PMID- 20041055
TI  - A more detailed classification of mild head injury in adults and treatment
      guidelines.
AB  - OBJECTIVE: The purpose of this study was to analyze risk factors that are
      associated with intracranial lesion, and to propose criteria for classification
      of mild head injury (MHI), and appropriate treatment guidelines. METHODS: The
      study was based on 898 patients who were admitted to our hospital with Glasgow
      Coma Scale (GCS) score of 13 to 15 between 2003 and 2007. The patients' initial
      computerized tomography (CT) findings were reviewed and clinical findings that
      were associated with intracranial lesions were analyzed. RESULTS: GCS score, loss
      of consciousness (LOC), age and skull fracture were identified as independent
      risk factors for intracranial lesions. Based on the data analysed in this study,
      MHI patients were divided into four subgroups : very low risk MHI patients are
      those with a GCS score of 15 and without a history of LOC or headache; low risk
      MHI patients have a GCS score of 15 and with LOC and/or headache; medium risk MHI
      patients are those with a GCS score of 15 and with a skull fracture, neurological
      deficits or with one or more of the risk factors; high risk MHI patients are
      those with a GCS score of 15 with abnormal CT findings and GCS score of 14 and
      13. CONCLUSION: A more detailed classification of MHI based on brain CT scan
      findings and clinical risk factors can potentially improve patient diagnosis. In
      light of our findings, high risk MHI patients should be admitted and treated in
      same manner as those with moderate head injury.

PMID- 20041056
TI  - Memory Dysfunctions after Mild and Moderate Traumatic Brain Injury : Comparison
      between Patients with and without Frontal Lobe Injury.
AB  - OBJECTIVE: The purpose of this study was to assess memory dysfunction in patients
      with mild and moderate traumatic brain injury (TBI) with and without frontal lobe
      injury (FLI). METHODS: The subjects were 110 TBI patients, who had recovered from
      the acute clinical phase, and comprised 20 (18.2%) mild TBI (MTBI) patients with
      FLI, 16 (14.5%) MTBI patients without FLI, 51 (46.4%) moderate TBI (MOTBI)
      patients with FLI and 23 (20.9%) MTBI patients without FLI. All patients were
      administrated the Korean version of the Memory Assessment Scale (K-MAS). RESULTS:
      Almost all the Summary Scale scores on the K-MAS failed to show any differences
      between TBI patients with and without FLI, but differences did emerge by types at
      severities. TBI patients with FLI showed higher Global Memory ability than TBI
      patients without FLI if their TBI was only mild, but when their TBI was more
      severe, this finding was reversed, and TBI patients with FLI showed lower Verbal
      and Global Memory abilities than TBI patients without FLI. CONCLUSION: Different
      kinds of assessment tools are needed for the measurement of memory abilities in
      TBI patients with FLI, and that the selection of the appropriate tool depends on
      the severity of the TBI.

PMID- 20041057
TI  - Surgical management and outcome of tethered cord syndrome in school-aged
      children, adolescents, and young adults.
AB  - OBJECTIVE: The adolescent presentation of tethered cord syndrome (TCS) is well
      recognized, but continues to pose significant diagnostic and management
      controversies. The authors conducted a retrospective study of clinical outcomes
      after surgical intervention in 24 school-aged children, adolescents, and young
      adults with TCS. METHODS: All 83 patients with a lipomyelomeningocele (LMMC)
      underwent untethering surgery for caudal cord tethering between 1987 and 2007.
      The clinical charts and follow-up data were reviewed. Of these patients, 24
      school-aged children, adolescents, and young adults with TCS were studied with
      respect to the clinical, radiologic, pathologic features, and surgical outcomes.
      RESULTS: Untethering procedures were performed in 24 patients (age range, 7-25
      years) for TCS of various origins (lipoma, lipomyelomeningocele, and tight filum
      terminale). Specific circumstances involving additional tugging of the already
      tight conus, and direct trauma to the back precipitated the onset of symptom in
      50% of the patients. Diffuse and non-dermatomal leg pain, often referred to the
      anorectal region, was the most common presenting symptom. Progressive
      sensorimotor deficits in the lower extremities, as well as bladder and bowel
      dysfunction, were also common findings, but progressive foot and spinal
      deformities were noted less frequently. The most common tethered lesions were
      intradural lipomas, thickened filum and fibrous band adhesions into the placode
      sac. The surgical outcome was gratifying in relation to pain and motor weakness,
      but disappointing with respect to resolution of bowel and bladder dysfunction. Of
      the 24 patients with TCS, pre-operative deficits improved after surgery in 14
      (58.3%), remained stable in 8 (33.4%), and worsened in 2 (8.3%). CONCLUSION: The
      pathologic lesions of tethered cord syndrome in school-aged children,
      adolescents, and young adults, are mostly intradural lipomas and tight filum. It
      is suggested that the degree of cord traction results in neurologic dysfunction
      in late life due to abnormal tension, aggravated by trauma or repeated tugging of
      the conus during exercise. Early diagnosis and adequate surgical release might be
      the keys to the successful outcome in school-aged children, adolescents, and
      young adults with TCS.

PMID- 20041058
TI  - The effect of hyaluronic Acid on the invasiveness of malignant glioma cells :
      comparison of invasion potential at hyaluronic Acid hydrogel and matrigel.
AB  - OBJECTIVE: Hyaluronidase (HAse), a degrading enzyme of hyaluronic acid (HA), is
      highly expressed in patients with malignant glioma. The purpose of this study was
      to verify whether HAse is related to the invasion of glioma cells. We also
      investigated if glioma cells with higher mobility in 2-dimensioal (2-D) method
      have also higher mobility at 3-dimensional (3-D) environment. METHODS: Malignant
      glioma cell lines (U87MG, U251MG, U343MG-A, and U373MG) were used, and their HAse
      expressions were evaluated by HA zymography. The migration ability was evaluated
      by simple scratch technique. The invasiveness of each cell lines was evaluated by
      Matrigel invasion assay and HA hydrogel invasion assay. In HA hydrogel invasion
      assay, colonies larger than 150 microm were regarded as positive ones and
      counted. Statistical analysis of migration ability and invasion properties of
      each cell lines was performed using t-test. RESULTS: In scratch test to examine
      migration ability of each cell lines, U87MG cells were most motile than others,
      and U343MG-A least motile. The HAse was expressed in U251MG and U343MG-A cell
      lines. However, U87MG and U373MG cell lines did not express HAse activity. In
      Matrigel invasion assay, the cell lines expressing HAse (U251MG and U343MG-A)
      were more invasive in the presence of HA than HAse deficient cell lines (U87MG
      and U373MG). In HA hydrogel invasion assay, the HAse-expressing cell lines formed
      colonies more invasively than HAse-deficient ones. CONCLUSION: Malignant Glioma
      cells expressing HAse were more invasive than HAse-deficient ones in 3
      dimensional environment. Therefore, it might be suggested that invasion of
      malignant gliomas is suppressed by inhibition of HAse expression or HA secretion.
      Additionally, the ability of 2-D migration and 3-D invasion might not be always
      coincident to each other in malignant glioma cells.

PMID- 20041059
TI  - A mouse model of photochemically induced spinal cord injury.
AB  - OBJECTIVE: A mouse model of spinal cord injury (SCI) could further increase our
      basic understanding of the mechanisms involved in injury and repair of the
      nervous system. The purpose of this study was to investigate whether methods used
      to produce and evaluate photochemical graded ischemic SCI in rats, could be
      successfully adapted to mice, in a reliable and reproducible manner. METHODS:
      Thirty female imprinting control region mice (weighting 25-30 g, 8 weeks of age)
      were used in this study. Following intraperitoneal injection of Rose bengal, the
      translucent dorsal surface of the T8-T9 vertebral laminae of the mice were
      illuminated with a fiber optic bundle of a cold light source. The mice were
      divided into three groups; Group 1 (20 mg/kg Rose bengal, 5 minutes
      illumination), Group 2 (20 mg/kg Rose bengal, 10 minutes illumination), and Group
      3 (40 mg/kg Rose bengal, 10 minutes illumination). The locomotor function,
      according to the Basso-Beattie-Bresnahan scale, was assessed at three days after
      the injury and then once per week for four weeks. The animals were sacrificed at
      28 days after the injury, and the histopathology of the lesions was assessed.
      RESULTS: The mice in group 1 had no hindlimb movement until seven days after the
      injury. Most mice had later recovery with movement in more than two joints at 28
      days after injury. There was limited recovery of one joint, with only slight
      movement, for the mice in groups 2 and 3. The histopathology showed that the mice
      in group 1 had a cystic cavity involving the dorsal and partial involvement of
      the dorsolateral funiculi. A larger cavity, involving the dorsal, dorsolateral
      funiculi and the gray matter of the dorsal and ventral horns was found in group
      2. In group 3, most of the spinal cord was destroyed and only a thin rim of
      tissue remained. CONCLUSION: The results of this study show that the
      photochemical graded ischemic SCI model, described in rats, can be successfully
      adapted to mice, in a reliable and reproducible manner. The functional deficits
      are correlated an increase in the irradiation time and, therefore, to the
      severity of the injury. The photothrombotic model of SCI, in mice with 20 mg/kg
      Rose bengal for 5 minutes illumination, provides an effective model that could be
      used in future research. This photochemical model can be used for investigating
      secondary responses associated with traumatic SCI.

PMID- 20041060
TI  - A case of calvarial hemangioma in cranioplasty site.
AB  - It is not uncommon for hemangiomas to occur in the calvarium, accounting for
      about 10% of the benign skull tumors. A 46-year-old man was presented with a
      palpable scalp mass on the left parietal region. Past medical history indicated
      that he had undergone cranioplasty 25 years prior due to a depressed skull
      fracture suffered from a traffic accident. Magnetic resonance imaging revealed
      mixed signal intensity mass on T1 -and T2-weighted images pushing a linear signal
      void lesion outward in the left parietal region. After total surgical removal
      along with cranioplasty, he was discharged without neurological deficits.
      Histological examination of the surgical specimen revealed a cavernous
      hemangioma. A skull hemangioma occurring at the site of a cranioplasty has not
      yet been reported. Therefore, authors report this case in combination with a
      pertinent literature review.

PMID- 20041061
TI  - External carotid artery angioplasty and stenting followed by superficial temporal
      artery to middle cerebral artery anastomosis.
AB  - A 31-year-old man presented with right hemiparesis, and magnetic resonance
      imaging revealed a small infarct at left basal ganglia. Digital subtraction
      angiography showed left cervical internal carotid artery (ICA) occlusion and
      severe stenosis of the ipsilateral external carotid artery (ECA) with collateral
      cerebral circulation fed by ECAs. Based on the results of a functional evaluation
      of cerebral blood flow, we performed preventive ECA angioplasty and stenting for
      advanced ECA stenosis to ensure sufficient blood flow to the superficial temporal
      artery. Eight weeks later, superficial temporal artery to middle cerebral artery
      (STA-MCA) anastomosis was performed. His postoperative course was uneventful and
      no additional transient ischemic attacks have occurred. To our knowledge, this is
      the first report of preventive angioplasty and stenting for advanced narrowing of
      an ECA before STA-MCA anastomosis for ipsilateral ICA occlusion.

PMID- 20041062
TI  - Recurrent subarachnoid hemorrhage after complete obliteration of intracranial
      aneurysm.
AB  - The authors report a case of recurrent subarachnoid hemorrhage (SAH) after
      complete occlusion of an intracranial aneurysm. It is known that regrowth of an
      aneurysm after the complete clipping is a rare event. For detection of
      recurrence, however, it may be necessary to follow up with the patient regularly
      after the initial operation for intracranial aneurysms, because re-rupture of an
      aneurysm can cause a fatal result, and the cumulative risk of a recurrent SAH is
      thought to be not low over time.

PMID- 20041063
TI  - Delayed carotid wallstent shortening resulting in restenosis following successful
      carotid artery angioplasty and stenting.
AB  - Carotid angioplasty and stenting (CAS) for carotid stenosis has been increasingly
      used as an alternative treatment in patients not eligible for surgery. Even
      though CAS can be performed relatively simply in many cases, various
      complications can occur. We report four cases of CAS using the Carotid Wallstent,
      which were complicated by delayed shortening of the stent, resulting in
      restenosis after successful CAS.

PMID- 20041064
TI  - Concomitant dual origin and fenestration of the left vertebral artery resembling
      dissection.
AB  - Dual origin and fenestration of the vertebral artery (VA) are very rare
      anomalies. Understanding of these variations, however, is important because they
      can be misdiagnosed as a VA dissection. A 42-year-old woman presented with motor
      weakness and sensory disturbance of the right upper extremity. Radiologic
      evaluations showed ectatic change in the right VA and an arteriovenous fistula
      between the right VA and the vertebral vein. We decided on endovascular occlusion
      of the proximal right VA and its fistulous portion. During the endovascular
      procedure, we had misunderstood the dual origin and fenestration of the VA as a
      dissection. Thus, failure to recognize these anomalies might result in
      unnecessary anticoagulation or therapeutic intervention. Clinicians should be
      alert to such VA variations when making a diagnosis and when planning any
      intervention or surgery involving the proximal VA.

PMID- 20041065
TI  - Remote cerebellar hemorrhage after lumbar spinal surgery.
AB  - Remote cerebellar hemorrhage (RCH) is rare but potentially lethal as a
      complication of spinal surgery. We recently experienced a case of RCH in a 61
      year-old man who showed mental deterioration after lumbar spinal surgery. There
      was dural tearing with subsequent cerebrospinal fluid (CSF) loss during the
      surgery. Brain computed tomography scan revealed cerebellar hemorrhage, 3rd and
      4th ventricular hemorrhage and pneumocephalus. He underwent suboccipital
      craniectomy and hematoma removal. The most important pathomechanism leading to
      RCH after spinal surgery has been known to be venous bleeding due to caudal
      sagging of cerebellum by rapid leak of large amount of CSF which seems to be
      related with this case. Dural repair and minimizing CSF loss after intraoperative
      dural tearing would be helpful to prevent postoperative RCH.

PMID- 20041066
TI  - Cervical disc herniation as a cause of brown-sequard syndrome.
AB  - The possible causes of Brown-Sequard Syndrome (BSS) have been frequently observed
      with spinal trauma and extramedullary spinal tumors, but the cervical disc
      herniation to cause BSS is rare. The authors present five cases of patients who
      were diagnosed with BSS resulting from cervical disc herniation, and the results
      of the literature in view of their distinctive symptoms and clinical outcomes.
      Postoperatively, the patients showed complete or almost complete recovery from
      their motor and sensory deficits. On the basis of our cases, it is important to
      diagnose it early by cervical magnetic resonance imaging, especially in the
      absence of the typical symptoms of cervical disc herniation or other obvious
      etiology of extremity numbness. Immediate surgical treatment is also essential
      for a favorable functional neurological recovery.

PMID- 20041068
TI  - Transfusion Medicine in the year 2025: Facts or Fantasy?

PMID- 20041067
TI  - Erratum: ERRATUM: Clinical and Radiological Outcomes of Anterior Cervical
      Interbody Fusion Using Hydroxyapatite Spacer.
AB  - [This corrects the article on p. 300 in vol. 46, PMID: 19893716.].

PMID- 20041069
TI  - Distribution of ABO and Rh-D blood groups in the Benin area of Niger-Delta:
      Implication for regional blood transfusion.
AB  - ABO and Rhesus (Rh) blood group antigens are hereditary characters and are useful
      in population genetic studies, in resolving medico-legal issues and more
      importantly in compatibility test in blood transfusion practice. Data on
      frequency distribution of ABO and Rh-D in Niger-Delta region of Nigeria are not
      available; hence we made an attempt to retrospectively analyze the records on the
      blood donors, transfusion recipients and patients attending antenatal care or
      some other medical interventions. Over a twenty-year period between 1986 and
      2005, a total of 160,431 blood samples were grouped for ABO and Rh-D at the blood
      bank of the University of Benin Teaching Hospital, Benin City, Nigeria. Blood
      group distribution among these samples showed phenotypes A, B, AB and O as
      23.72%, 20.09%, 2.97% and 53.22%, respectively. The Rh-D negative phenotype was
      found among 6.01% of the samples tested.

PMID- 20041070
TI  - The pyramid model as a structured way of quality management.
AB  - Three quality systems that can be used in blood establishments are briefly
      explained. The Pyramid model is described as a tool to manage the quality
      systems. Finally, some experiences in other countries are given to prove the
      validity of the system.

PMID- 20041071
TI  - Iron status of regular voluntary blood donors.
AB  - BACKGROUND: Our blood bank is a regional blood transfusion centre, which accepts
      blood only from voluntary donors. AIM: The aim is to study iron status of regular
      voluntary donors who donated their blood at least twice in a year. MATERIALS AND
      METHODS: Prior to blood donation, blood samples of 220 male and 30 female
      voluntary donors were collected. Control included 100 each male and female
      healthy individuals in the 18- to 60-year age group, who never donated blood and
      did not have any chronic infection. In the study and control groups, about 10%
      subjects consumed non-vegetarian diet. After investigation, 85 males and 56
      females having haemoglobin (Hb) levels above 12.5 g/dl were selected as controls.
      Donors were divided into </=10, 11-20, 21-50 and >50 blood donation categories.
      Majority of the donors in >50 donation category donated blood four times in a
      year, whereas the remaining donors donated two to three times per year.
      Haematological parameters were measured on fully automatic haematology analyzer,
      serum iron and total iron-binding capacity (TIBC) by biochemical methods,
      ferritin using ELISA kits and transferrin using immunoturbidometry kits.
      Iron/TIBC ratio x 100 gave percentage of transferrin saturation value.
      STATISTICAL ANALYSIS: Statistical evaluation was done by mean, standard
      deviation, pair t-test, chi(2) and anova (F-test). RESULTS: Preliminary analysis
      revealed that there was no significant difference in the iron profile of
      vegetarian and non-vegetarian subjects or controls and the donors donating <20
      times. Significant increase or decrease was observed in mean values of various
      haematological and iron parameters in donors who donated blood for >20 times (P <
      0.001), compared to controls. Anaemia, iron deficiency and depletion of iron
      stores were more prevalent in female donors (P < 0.05) compared to males and
      especially in those male donors who donated their blood for more than 20 times.
      CONCLUSION: Regular voluntary blood donors should receive iron supplementation to
      prevent iron deficiency and depletion in iron stores.

PMID- 20041072
TI  - Status of blood transfusion services in Iran.

PMID- 20041073
TI  - Emergency therapeutic leukapheresis in a case of acute myeloid leukemia M5.
AB  - Cell separators in India are routinely used for plateletpheresis, peripheral
      blood stem cell collections and therapeutic plasma exchange. Therapeutic
      leukapheresis, particularly as an emergency procedure, has been uncommonly
      performed and reported. Here, a case of a 53-year-old male, diagnosed with acute
      myeloid leukemia subtype M5 (AML M5) with hyperleukocytosis, who underwent
      emergency leukaphereis, is reported. After two procedures, there was a decrease
      of WBC count by 85%, which enabled cytotoxic therapy to be initiated.

PMID- 20041074
TI  - Fatal drug-induced immune hemolytic anemia due to cefotetan; A case study.
AB  - A case is described here of drug-induced immune hemolytic anemia (DIIHA) due to
      cefotetan administered to a post-partum woman who received the drug for infection
      prophylaxis at the time of caesarean section. Renewed fatal hemolysis occurred
      when the drug was given a second time 12 days after the first dose. The initial
      immunohematologic findings included a positive direct antiglobulin test (DAT) due
      to IgG and complement coating of the patient's RBCs as well as an eluate that did
      not react with RBCs in the absence of drug. The antibody was drug-dependent,
      reacting with both drug-coated RBCs as well as when the drug was added to a
      mixture of her serum and donor RBCs. Cefotetan has been a common cause of this
      uncommon problem. The clinical features of cefotetan DIIHA, classification of
      drug-induced antibodies, and the differential diagnosis of a positive DAT are
      briefly discussed.

PMID- 20041075
TI  - Prices of blood units in South East Asia.

PMID- 20041076
TI  - An update of blood donor recruitment and retention in Hong Kong.
AB  - A healthy blood donor pool has to be well maintained in order to achieve self
      sufficiency in blood supply. Not only should new and young donors should be
      attracted and recruited into the pool so as to compensate the loss from drop out
      and deferred donors. At the same time, previous donors should be also actively
      retained to ensure they can come regularly. The status of donor recruitment and
      retention in Hong Kong is reviewed here to highlight the current difficulties in
      coping with increasing blood demand from an ageing population, stringent donor
      eligibility criteria and quality requirement in the blood collection. With a
      systemic analysis of the donation pattern, proposal is put forward to tackle the
      challenging problems.

PMID- 20041077
TI  - Does transfusion of residual cardiopulmonary bypass circuit blood increase
      postoperative bleeding? A prospective randomized study in patients undergoing on
      pump cardiopulmonary bypass.
AB  - OBJECTIVE: Homologous blood transfusion after open heart surgery puts a
      tremendous load on the blood banks. This prospective randomized study evaluates
      the efficacy of infusing back residual cardiopulmonary bypass (CPB) circuit i.e.,
      pump blood as a means to reduce homologous transfusion after coronary artery
      bypass surgery (CABG) and whether its use increases postoperative drainage.
      MATERIALS AND METHODS: Sixty-seven consecutive patients who underwent elective
      CABGs under CPB were randomized into 2 groups: (1) cases where residual pump
      blood was used and (2) controls where residual pump blood was not used. Patients
      were monitored for hourly drainage on the day of surgery and the 1(st)
      postoperative day and the requirements of homologous blood and its products. Data
      were matched regarding change in Hemoglobin, Packed Cell Volume and coagulation
      parameters till 1st postoperative day. All cases were followed up for three
      years. RESULTS: There was a marginal reduction in bleeding pattern in the early
      postoperative period in the cases compared to controls. The requirement of
      homologous blood and its products were also reduced in the cases. CONCLUSIONS:
      The use of CPB circuit blood is safe in the immediate postoperative period. The
      requirement of homologous blood transfusion can come down if strict transfusion
      criteria are maintained.

PMID- 20041078
TI  - Behavior disparities towards blood donation in Sikkim, India.
AB  - BACKGROUND: The aim of the current research was to determine disparities in blood
      donation motives among the general mass of Sikkim. AIMS: To identify the reasons
      for people donating and not donating blood voluntarily. SETTINGS AND DESIGN:
      Population based cross-sectional study in Gangtok, East Sikkim. MATERIALS AND
      METHODS:  PARTICIPANTS: 300 adults by two-stage cluster sampling technique.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: Correlates of attitudes towards blood
      donation. DATA COLLECTION PROCEDURE: The data collection tool used for the study
      was a pre-tested structured interview schedule by which the principal
      investigator collected the data using interview technique. STATISTICAL ANALYSIS
      USED: Percentages and ODDS ratio were used in this study. RESULTS AND
      CONCLUSIONS: Out of 300 respondents, overwhelming majority (78.7%) of the
      respondents in the present study felt that people donate blood to save a friend
      or a relative. On the contrary, minority respondents (46%) were ready to donate
      blood voluntarily. Only 12.7% of the respondents had ever donated blood while
      87.3% had never donated. Among ever donors, gender wise men donors were found to
      be more; 89% were married, half were from the 30 to 39 years age group. As the
      per-capita income or level of education increased, so did the percent of blood
      donors.

PMID- 20041079
TI  - Effect of antifibrinolytic drugs on transfusion requirement and blood loss during
      orthotopic liver transplantation: Results from a single center.
AB  - BACKGROUND: During orthotopic liver transplantation (OLT), activation of the
      fibrinolytic system can contribute significantly to perioperative bleeding.
      Prophylactic administration of antifibrinolytic agents has been shown to reduce
      blood loss and the need for allogenic transfusion. OBJECTIVE: To study the effect
      of antifibrinolytics on requirement of blood components, blood loss and operative
      time during OLT in patients with end stage liver disease, reporting to a single
      centre. MATERIALS AND METHODS: Consecutive patients who underwent OLT at this
      centre during the period February 2003-October 2007 were the subjects of this
      study. Based on the individual anesthesiologist's preference, patients were
      assigned to receive either two million units of aprotinin (AP) as a bolus
      followed by 5,00,000 units/hour or 10 mg/kg tranexamic acid (TA) as a bolus
      followed by 10 mg/kg every six to eight hours, administered from the induction
      till the end of the surgery. Transfusion policy was standardized in all patients.
      Intraoperative red cell salvage was done wherever possible. The effect of these
      two antifibrinolytic drugs on transfusion requirement was evaluated as a whole
      and in a sub group of patients from each treatment group and compared with a
      concurrent control group that did not receive antifibrinolytic drugs. RESULTS:
      Fifty patients (40 M / 10 F, 44 adults, 6 pediatric patients) underwent OLT in
      the study period. Fourteen patients were given AP, 25 patients were given TA and
      11 patients did not receive any of the agents(control group). The median volume
      of total blood components transfused in antifibrinolytic group (n = 39) was 4540
      ml(0-19,200ml), blood loss 5 l(0.7-35l) and operative time 9h (4.5-17h) and that
      of control group(n = 11) was 5700 ml(0-15,500ml), 10 l(0.6-25 l) and 9h (6.4
      15.8h) respectively. The median volume of blood transfusions, blood loss and
      operative time was lesser in AP group(n = 14) than that of TA group(n = 25).
      CONCLUSION: There is definite decrease in transfusion requirement, blood loss and
      operative time in the patients who received antifibrinolytic drugs than that of
      patients who did not receive. Because of the small sample size, comparisons
      carried between different groups did not show statistical significance.
      Prophylactic use of antifibrinolytics during OLT, possibly helps in blood
      conservation.

PMID- 20041080
TI  - Seroprevalence of human immunodeficiency virus in Nepalese blood donors: A study
      from three regional blood transfusion services.
AB  - BACKGROUND AND OBJECTIVE: The likelihood of human immunodeficiency virus (HIV)
      infection occurring in recipients of HIV seropositive blood is close to 100%.
      Transmission during window period is still possible even each unit of blood is
      tested for anti-HIV 1 and 2 antibodies. The possibility of window period
      transmission would be minimized if blood is collected from low risk targeted
      general public. A continuous surveillance data might prove valuable for concerned
      authorities to assess their service and plan for further improvements in
      transfusion safety. Our aim was to determine the seroprevalence of HIV in
      regional blood transfusion services located at three developmental regions of
      Nepal and compare the results. MATERIALS AND METHODS: A total of 16,557 blood
      donors were screened for anti-HIV 1 and 2 antibodies in three blood transfusion
      services viz. 5,351 donors in Morang, 5,211 in Banke, 5,995 in Kaski by using
      rapid anti HIV 1 and 2 Test. The statistical significance of difference in
      seroprevalence was tested by Fisher's Exact Test using the statistical software
      'Winpepi ver 3.8'. RESULTS: The overall seroprevalence of HIV among blood donors
      in the regional blood transfusion services was 0.054% (9/16557) and 100%
      seropositivity was among male donors. The individual seroprevalence in Morang was
      0.019%, in Banke was 0.095% and in Kaski was 0.05%. The HIV seroprevalence was
      not significantly different in regional blood transfusion services of Nepal
      (Fisher Exact Test, P = 0.2096). CONCLUSION: The seroprevalence in the regional
      blood transfusion service of Nepal was quite low and the seroprevalence rate was
      not significantly different.

PMID- 20041081
TI  - Rh antigen expression during erythropoeisis: Comparison of cord and adult derived
      CD34 cells.
AB  - OBJECTIVES: Concentrations of O(2) and CO(2) in the fetal circulation differ to
      that in maternal blood. Previous studies done in algae demonstrate the functional
      role of Rh antigen as CO(2) transporter. As a preliminary study, it was the aim
      of this project to compare the expression of Rh polypeptides on cord and adult
      red blood cell progenitors during ex vivo proliferation and differentiation of
      CD34(+) cells during erythropoeisis. MATERIALS AND METHODS: CD34 positive
      hematopoeitic progenitor cells were isolated from umbilical cord blood and adult
      peripheral blood using an immunomagnetic system and cultured in serum free medium
      containing erythropoietin in order to compel them along the erythroid lineage.
      Cultured cells were analyzed for cell surface marker expression by flow
      cytometry, using monoclonal antibodies to RhAG, Glycophorin A, Rh polypeptides,
      CD47 and Band 3. Cytospin analysis was also done to study the morphology of
      cultured cells. RESULTS: The appearance of cell surface markers analyzed on
      different days of culture varied slightly between samples. There was no evidence
      to suggest that RhAG, GPA, CD47 and Band 3 expression was any different between
      adult and cord derived cells. Nevertheless, the results of Rh antigenic
      expression suggest a reasonable difference between the two groups with adult
      sample derived cells showing higher and earlier expression than cord blood
      derived cells. These preliminary findings require further investigation.
      CONCLUSION: Comparing the expression of cell surface markers especially Rh
      polypeptides between adult and cord blood derived erythroid progenitors might
      assist in discerning their functions and could be valuable in the study of
      erythropoeisis.

PMID- 20041082
TI  - Anti-M: Report of two cases and review of literature.
AB  - Anti-M is a fairly common naturally occurring antibody with rarely causing
      hemolytic transfusion reactions or hemolytic disease of the newborn. Most anti-M
      are not active at 37 degrees C and can generally be ignored in transfusion
      practice. However, we did not find this antibody to be fairly common and detected
      only two cases of anti-M in the past three years. We describe these two cases;
      one 'immunizing' type and other 'naturally occurring' and review the literature.
      The immunizing type was reactive at 37 degrees C as well as AHG phase of testing
      with IgG component, and showing dosage effect while the other was 'naturally
      occurring' reactive well below 37 degrees C. Though rare, sometimes these
      antibodies can be of clinical significance when the antibody detected is reactive
      at 37 degrees C and AHG phase. When the antibody is active at 37 degrees C, M
      antigen negative cross match compatible red cell unit should be given.

PMID- 20041083
TI  - The approach taken to reducing the risk of transfusion related acute lung injury
      in Canada.
AB  - Transfusion related acute lung injury (TRALI) has become a major reported cause
      of severe transfusion reactions and mortality. Over the past four years
      significant changes have been taken in Canada in order both to improve the
      recognition of the risk and to decrease its incidence. An international meeting
      was held in April of 2004 entitled "Towards an Understanding of TRALI". As a
      result of the analysis and recommendations from this meeting, the Canadian Blood
      Services established an ongoing review committee and established a laboratory
      diagnostic facility to identify at risk donors and recipients. A system has been
      developed to identify implicated donors and exclude them from the blood donor
      pool. Other steps have been taken to exclude potentially high risk donors, such
      as previously pregnant females, from the plasma and platelet donor pool. A
      considerable amount of education also has been offered to clinical services in
      the country. This paper summarizes the definitions, categorizations of implicated
      donors, and the ongoing precautionary activities related to plasma products.
      Noted within the article are the methods used for locating and selecting data.
      These were primarily based on the international TRALI conference in 2004, and
      from ongoing discussions and information provided by the Canadian Blood Services
      TRALI Review Committee. No ethics referral or approval was requested, and a
      summary is included in the article.

PMID- 20041084
TI  - The progress of South Korean blood transfusion services (2004-2006).

PMID- 20041085
TI  - Quality issues of laboratory reagents.

PMID- 20041087
TI  - Can there be blood units of high and low quality?

PMID- 20041086
TI  - Reply.

PMID- 20041088
TI  - Studies on the ABH-Iso-Agglutinins in serum, saliva and milk from mothers with
      "Bombay" (Oh) phenotype.
AB  - BACKGROUND: ABO blood group iso-antibodies are naturally occurring antibodies
      found in serum and other body fluids. METHODS: Serum, saliva and milk samples
      from 5 mothers identified as "Bombay" phenotype were tested for ABH-iso
      antibodies by routine serological techniques. RESULTS: All the five mothers
      showed presence of iso-antibodies in the samples tested. Higher titer values in
      milk than their serum were observed on subjects whose samples were collected in
      immediate post-partum phase as compared to those whose samples were collected
      after a lapse of a few months. CONCLUSION: High titer iso-agglutinins against ABH
      antigens were detected in milk samples besides their presence in saliva as well
      as serum.

PMID- 20041089
TI  - Post-splenectomy response in adult patients with immune thrombocytopenic purpura.
AB  - Splenectomy has been the conventional surgical treatment for patients with Immune
      Thrombocytopenic Purpura (ITP). AIM: To define response to surgical therapy, pre
      operative factors influencing outcome and tolerability of surgery in adult
      patients undergoing splenectomy for ITP. METHOD: We analyzed prospectively
      maintained data of 33 patients who were diagnosed as ITP and underwent
      splenectomy over the last 10 years. The age, presenting complaints, bleeding
      manifestations, clinical details and other investigations were noted. Details of
      immediate pre-operative administration of blood transfusions, platelet
      transfusions and other forms of therapy were also recorded. Operative details
      with regards to blood loss and the presence of accessory spleens were obtained.
      Postoperative course in terms of clinical improvement, rates of complications and
      platelet counts was also noted. RESULTS: Skin petechiae and menorhhagia were
      common presenting symptoms in patients (mean age 26.5+/-10.5 yrs) with ITP.
      Eighteen patients underwent splenectomy for failure of therapy and fifteen for
      relapse on medical treatment. Mean platelet bags transfused in immediate pre
      operative period were 2.8+/-0.8. Mean intra-operative blood loss was 205+/-70.5
      ml. Accessory spleens were removed in 1 case (3.03%). The immediate postoperative
      response was complete in 19 cases (57.58%) and partial in 13 cases (39.39%). The
      platelet counts increased significantly from 23142+/-12680/ microL (Microliter)
      (mean +/- SD) preoperatively to 170000+/-66000/microL (Microliter) within 24-48
      hours after splenectomy (P < 0.05). The mean platelet count was
      165000+66000/microL (Microliter) at the end of one month when steroids were
      tapered off gradually. Four patients (12.12%) had complications (one each of
      wound hematoma, wound infection, splenic fossa collection and upper GI
      hemorrhage) in postoperative period but all responded to therapy. One relapsed
      patient was detected with accessory spleen and responded after re-surgery.
      Response to splenectomy was better in young patients and in those patients who
      had higher immediate post-splenectomy thrombocytosis. CONCLUSIONS: Splenectomy is
      safe and effective therapy in ITP patients with no response to steroids and
      relapse after medical therapy. Response to splenectomy was more in young patients
      and in those patients who had higher immediate post-splenectomy thrombocytosis.

PMID- 20041090
TI  - The use of a volatile anesthetic regimen protects against acute normovolemic
      hemodilution induced myocardial depression in patients with coronary artery
      disease.
AB  - BACKGROUND: Previous studies indicated that acute normovolemic hemodilution (ANH)
      was associated with a depression of myocardial function in coronary surgery
      patients with baseline heart rate faster than 90 bpm. It was suggested that this
      phenomenon could be explained by the occurrence of myocardial ischemia. In the
      present study, we hypothesized that the cardioprotective properties of a volatile
      anesthetic regimen might protect against the ANH related myocardial functional
      impairment. MATERIALS AND METHODS: Forty elective coronary surgery patients with
      baseline heart rate faster than 90 bpm were randomly allocated to receive
      different anesthetic regimens. Group A (n = 20) received midazolam-based
      anesthesia. Group B (n = 20) received a sevoflurane-based anesthesia. Five-lead
      electrocardiogram, pulse oximetry, capnography, radial arterial pressure, and
      Swan Ganz continuous thermodilution cardiac output via right internal jugular
      vein were monitored. Measurements were obtained before and after ANH. Data were
      compared using paired t test. All data were expressed as mean +/- SD. Data were
      considered significant if P < 0.05. RESULTS: After ANH, systemic vascular
      resistance was slightly decreased in group A while there was a significant
      decrease in group B. In group A, cardiac output was slightly decreased from
      5.07+/-1.17 l/min to 5.02+/-1.28 l/min after ANH, whereas in group B, cardiac
      output was significantly increased from 4.84+/-1.21 l/min to 6.02+/-1.28 l/min
      after ANH. CONCLUSION: In coronary surgery patients, with baseline heart rate
      faster than 90 bpm, anesthesia with sevoflurane during ANH was associated with an
      improvement in myocardial function after ANH, which was not present in patients
      anesthetized with midazolam.

PMID- 20041091
TI  - Clinical significance of antibody to hepatitis B core antigen in multitransfused
      hemodialysis patients.
AB  - BACKGROUND: In spite of the progress made in the prevention of transfusion
      transmitted infections over the last few years, transmission of HBV infection
      through transfusion of HBsAg negative blood has been documented. OBJECTIVES: To
      assess the frequency and clinical significance of anti-HBc in multitransfused
      hemodialysis patients. MATERIALS AND METHODS: One hundred and forty-three
      hemodialysis patients who had been receiving blood regularly with an average of
      39.4 +/- 7.579 months on hemodialysis were enrolled in this study. HBV markers
      (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy
      controls by the ELISA technique. The following data were obtained for all
      patients: socio demographic data, number of blood transfusions and some
      laboratory investigations. RESULTS: In our patients, anti-HBc was positive in 9%,
      anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%,
      meanwhile no patients were positive for HBsAg alone. In patients with only
      positive anti-HBc, the levels of anti-HBc were significantly related to abnormal
      results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27),
      18 patients had abnormal liver function, and 9 patients had normal liver function
      with no significant difference between them. CONCLUSIONS: This study suggests
      that hepatitis B prevalence in our multitransfused hemodialysis patients is far
      in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg
      in the blood of hemodialyzed patients may not be sufficient to ensure lack of
      circulating HBV, and isolated positivity of anti-HBc may be a possible indicator
      of active hepatitis B infection.

PMID- 20041092
TI  - Current concepts in platelet transfusion.
AB  - This is the era of component therapy. Therefore there is a need for rational use
      of platelet concentrate. Lot of knowledge has been added recently in the field of
      platelet specially about the platelet rich plasma and its application in clinical
      practice. The current review focuses on improvement in preparation of platelet
      rich plasma, the procedure to make the same more safe and its rational use.
      Furthermore newer aspects of platelet concentrate use in surgical practice and
      for regenerative medicine has also been discussed. It also covers some progress
      and hurdles in preparation of platelet substitutes.

PMID- 20041093
TI  - Status report of the blood transfusion services in Myanmar.

PMID- 20041094
TI  - Hyperhemolysis in a patient with beta-thalassemia major.
AB  - A case of hyperhemolysis in a 2-year-old boy with beta thalassemia major was
      noted. After several transfusions, he developed hyperhemolysis with a positive
      (C3d only) direct antiglobulin test (DAT) and no clinically significant RBC allo-
      or auto-antibodies. (There was a weak cold antibody, showing a narrow thermal
      range). Because there was no significant improvement with steroid and
      immunoglobulin infusions, cyclophosphamide therapy was tried with notable
      success.

PMID- 20041095
TI  - Time for global efforts with clinical trials for advanced cervical cancer
      patients.

PMID- 20041096
TI  - Major clinical research advances in gynecologic cancer 2009.
AB  - In this review, we summarized nine major clinical advances in gynecology which
      occurred in 2009. For cervical cancer, the role of human papillomavirus (HPV)
      test as a screening test, the efficacy of HPV vaccine for middle-aged women,
      randomized controlled trial (RCT) regarding concurrent chemoradiation using
      gemcitabine plus cisplatin, and the efficacy of pazopanib for metastatic or
      recurrent disease were chosen. For endometrial cancer, the necessity of
      systematic pelvic lymphadenectomy in early endometrial cancer was reviewed. For
      ovarian cancer, the timing of treatment initiation for recurrent ovarian cancer,
      dose-dense chemotherapy as postoperative adjuvant treatment, the best
      chemotherapy regimen for platinum-sensitive recurrent ovarian cancer, and the
      efficacy of target agents were selected. In addition, the results of RCT testing
      the benefit of ginger in preventing post-chemotherapy nausea were examined.

PMID- 20041097
TI  - Correlation between tumor volume response to radiotherapy and expression of
      biological markers in patients with cervical squamous cell carcinoma.
AB  - OBJECTIVE: To determine the factors associated with tumor volume response to
      radiotherapy (RT) in cervical cancer patients, and the relationship between the
      tumor volume response and alteration of the expression of biological markers
      during RT. METHODS: Twenty consecutive patients with cervical squamous cell
      carcinoma who received definitive RT were enrolled. Tumor volumes were calculated
      by MRI examinations performed at the start of RT (pre-RT), at the fourth week of
      RT (mid-RT), and 1 month after RT completion (post-RT). Two serial punch biopsies
      were performed at pre- and mid-RT, and immunohistochemical staining was performed
      for cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR). RESULTS:
      For the pre-RT evaluation, fourteen (70%) and eleven (55%) patients showed
      positive immunoreactivity for COX-2 and EGFR, respectively. Among the seven
      patients whose median percentage residual tumor at mid-RT (V2R) was greater than
      0.5, seven (100%, p=0.0515) and five (71.4%, p=0.3742) patients showed positive
      immunoreactivity for COX-2 and EGFR, respectively. The logistic regression
      analysis showed that positive immunoreactivity for both COX-2 and EGFR at pre-RT
      were associated with V2R (p=0.0782). For the mid-RT evaluation, eight cases
      showed an interval increase in the distribution of immunoreactivity for COX-2,
      and six out of the eight patients had a V2R greater than 0.5 (p=0.2222).
      CONCLUSION: The poor mid-RT tumor response was associated with the coexpression
      of COX-2 and EGFR.

PMID- 20041098
TI  - Weekly cisplatin or gemcitabine concomitant with radiation in the management of
      locally advanced carcinoma cervix: results from an observational study.
AB  - OBJECTIVE: The use of non-platinum drugs in concurrent chemoradiation in
      carcinoma cervix has not been well explored and hence a two arm study was planned
      to compare the outcome of concomitant cisplatin or gemcitabine in locally
      advanced carcinoma cervix. METHODS: Thirty six patients were evaluated in this
      study for response rates and complications. These patients were divided into two
      arms, sixteen patients in the cisplatin arm and twenty patients in the
      gemcitabine arm. Cisplatin and gemcitabine were given as i.v. infusion at doses
      of 40 mg/m(2) and 150 mg/m(2) respectively for five weeks concomitant with
      radiotherapy. All patients had received pelvic radiotherapy to a dose of 50 Gy/25
      fraction/5 weeks by four field box technique followed by high-dose-rate
      brachytherapy (3 sessions, each of 7.5 Gy to point A). RESULTS: Median follow up
      was of 10.4 months (range, 3 to 36 months) and 10.9 months (range, 2 to 49
      months) in the cisplatin and gemcitabine arms, respectively. At first follow up,
      68.8% in the cisplatin arm and 70% in the gemcitabine arm had achieved complete
      response (p=0.93). Similar response rates were noted in different stages in both
      arms. None of the patients except one developed grade 4 toxicity. Similar
      toxicity profiles were observed in both arms. Local disease control, distant
      disease free survival and overall survival was 68.8% vs. 70%, 93.8% vs. 85%,
      68.8% vs. 60% in the cisplatin and gemcitabine arms, respectively. CONCLUSION:
      Weekly gemcitabine had similar disease control and tolerable toxicity profile
      with cisplatin. Gemcitabine may be used as an alternative to cisplatin in
      patients with compromised renal function.

PMID- 20041099
TI  - Treatment outcomes and prognostic factors in uterine cervical cancer patients
      treated with postoperative extended field radiation therapy.
AB  - OBJECTIVE: To evaluate treatment outcomes and prognostic factors in uterine
      cervical cancer patients treated with postoperative extended field radiation
      therapy (POEFRT) with or without chemotherapy. METHODS: Between 1983 and 2006, 35
      patients with a pathologically confirmed positive para-aortic node (PAN) or
      common iliac node (CIN) who underwent a radical hysterectomy with bilateral
      pelvic lymph node dissection and PAN dissection received POEFRT with (N=23) or
      without (N=12) chemotherapy. Prognostic factors such as age, stage, size,
      parametrium invasion, lymphovascular space invasion, nodal station, depth of
      stromal invasion and use of chemotherapy were analyzed. RESULTS: With a median
      follow-up of 44 months, the 5-year overall survival (OS), disease-free survival
      (DFS), distant failure-free survival (DFFS) and loco-regional failure-free
      survival rates were 51%, 51%, 59% and 93%, respectively. The use of chemotherapy
      significantly improved the 5-year OS rate (61% vs. 48%, p=0.004), the 5-year DFS
      rate (54% vs. 38%, p=0.004) and the 5-year DFFS rate (57% vs. 48%, p=0.009). PAN
      involvement resulted in a compromised 5-year DFS rate (42% vs. 73%, p=0.002) and
      5-year DFFS rate (47% vs. 82%, p=0.004) as compared to CIN involvement. Grade 3
      or higher hematological toxicity was observed more frequently in patients who
      received POEFRT combined with chemotherapy as compared to patients who received
      POEFRT alone (52% vs. 17%, p=0.04). CONCLUSION: The use of POEFRT resulted in an
      excellent loco-regional control rate. The addition of chemotherapy may improve
      outcome in patients who have received POEFRT, but with higher manageable
      toxicity.

PMID- 20041100
TI  - The utility of the human papillomavirus DNA load for the diagnosis and prediction
      of persistent vaginal intraepithelial neoplasia.
AB  - OBJECTIVE: We evaluated the human papillomavirus (HPV) DNA load for the diagnosis
      and prediction of persistent vaginal intraepithelial neoplasia (VAIN). METHODS: A
      retrospective review of the medical records of patients with a pathological
      diagnosis of VAIN was performed. Eligible women (N=48) were followed for cytology
      and HPV DNA test, and colposcopic biopsies were taken at 3- to 6-month intervals.
      Thirty-seven patients were followed for more than 6 months; their HPV DNA test
      results were compared to the cytology results for the prediction of disease
      prognosis. RESULTS: The degree of VAIN was more severe in patients with a high
      initial HPV DNA load (p=0.009). Patients with VAIN 2 and VAIN 3 were older than
      those with VAIN 1 (p=0.005 and 0.008, respectively). In 26 out of 37 patients
      (70.3%), the VAIN resolved. The other patients had persistent lesions with no
      progression to invasive vaginal carcinoma. The last follow-up HPV DNA load was
      significantly higher in the group with persistent VAIN compared to the group with
      resolved VAIN (p<0.0001). Negative cytology was observed in 25 out of 26 patients
      in the VAIN resolved group and in nine out of 11 patients in the VAIN persistent
      group (p=0.205). CONCLUSION: These results suggest that the HPV DNA test,
      especially for viral load, was more effective for the diagnosis and prediction of
      persistent VAIN than cytology.

PMID- 20041101
TI  - A hospital-based case-control study of identifying ovarian cancer using symptom
      index.
AB  - OBJECTIVE: Recently, a symptom index for identification of ovarian cancer, based
      on specific symptoms along with their frequency and duration, was proposed. The
      current study aimed at validation of this index in Korean population. METHODS: A
      case-control study of 116 women with epithelial ovarian cancer and 209 control
      women was conducted using questionnaires on eight symptoms. These included
      pelvic/abdominal pain, urinary urgency/frequency, increased abdominal
      size/bloating, difficulty eating/feeling full. The symptom index was considered
      positive if any of the 8 symptoms present for <1 year that occurred >12 times per
      month. The symptoms were compared between ovarian cancer group and control group
      using chi-square test. Logistic regression analysis was used to determine whether
      the index predicted cancer. Sensitivity and specificity of the symptom index were
      also determined. RESULTS: The symptom index was positive in 65.5% of women with
      ovarian cancer, in 31.1% of women with benign cysts, and in 6.7% of women on
      routine screening (ps<0.001). Significantly higher proportion of ovarian cancer
      patients were positive for each symptom as compared with control group
      (ps<0.001). Results from the logistic regression indicated that the symptom index
      independently predicted cancer (p<0.001; OR, 10.51; 95% CI, 6.14 to 17.98).
      Overall, the sensitivity and specificity of the symptom index were 65.5% and
      84.7%, respectively. Analyses of sensitivity by stage showed that the index was
      positive in 44.8% of patients with stage I/II disease and in 72.9% of patients
      with stage III/IV disease. CONCLUSION: The current study supported previous
      studies suggesting that specific symptoms were useful in identifying women with
      ovarian cancer.

PMID- 20041102
TI  - Epstein-Barr virus-transformation of B-cell lines in ovarian cancer patients:
      feasibility of genomic storage for unlimited use.
AB  - OBJECTIVE: The aim of the current study is to test whether immortalized B
      lymphocyte cell line via Ebstein-Barr virus (EBV) transformation is feasible and
      can be an unlimited source of genome wide study. METHODS: We obtained peripheral
      whole blood from 5 ovarian cancer patients and immortalized the B-cell lines
      using EBV transformation. The success rate was analyzed and the bio-identity of
      the genome was performed using human leukocyte antigen (HLA) identity test.
      RESULTS: EBV transformation was successful in all 5 cases (95% confidence
      interval, 46.3% to 100%). After cryopreservation of EBV-transformed B-cell lines
      and subsequent thawing, we observed that all cell lines were viable and
      proliferative. To check bio-identity, HLA-A, B, and DR were tested between the
      genome of the original samples and the transformed samples. The HLA typing
      revealed that all observed HLA-A, B, and DR type was identical in 5 cases before
      and after EBV-transformation. CONCLUSION: The current results suggest that EBV
      transformation of peripheral blood is an efficient tool in genome banking. The
      EBV-transformed B-cell lines may be a valuable resource of genome in multi-center
      translational research by the Korean Gynecologic Oncology Group.

PMID- 20041103
TI  - Chemotherapy and patient co-morbidity in ventral site hernia development.
AB  - OBJECTIVE: The risk factors associated with early ventral site hernia development
      following cancer surgery are ill defined and associated with an undetermined
      incidence. METHODS: We analyzed 1,391 gynecologic cancer patient charts to
      identify the number of post-operative ventral site hernias over a nearly 6 year
      period. The following study variables were noted for evaluation: patient
      demographics, disease co-morbidity (hypertension, cardiovascular disease,
      diabetes), body mass index (BMI), treatment (e.g., chemotherapy regimen), intra
      operative (e.g., bleeding) and postoperative (e.g., infection) complications,
      time to hernia development and length of hospital stay. RESULTS: Twenty-six
      gynecologic cancer patients who developed a post-operative ventral hernia and
      subsequently underwent herniorrhaphy by our gynecologic oncology service were
      identified. The patient group's overall time to initial hernia development was
      11.23 months. Following a multiple regression analysis, we found that treatment
      (e.g., bevacizumab, liposomal doxorubicin or radiotherapy associated with
      compromised wound healing [p=0.0186] and disease co-morbidity [0.0432]) were
      significant prognostic indicators for an accelerated time to hernia development.
      Moreover, five patients underwent treatment associated with compromised wound
      healing and also had disease co-morbidity. In this sub-group, post-operative
      hernia development occurred more rapidly (3.8 months) than the overall group of
      patients. BMI and age did not impact time to hernia development (p>0.05).
      CONCLUSION: In the present gynecologic cancer patient series, a tendency for
      early post-operative hernia development appeared to coincide with treatment
      associated with compromised wound healing and disease co-morbidity. Gynecologic
      cancer surgeons should anticipate this potential complication and consider
      employing prophylactic intra-operative mesh to potentially prevent this
      condition.

PMID- 20041104
TI  - A case of advanced gynecologic pelvic tumors showing the diagnostic utility of
      HPV analysis.
AB  - Gynecologic malignancies may have similar histological characteristics. This may
      lead to difficulties in determining the origin of the cancer and to distinguish a
      synchronous neoplasm from a metastatic cancer in advanced cases. Recently, we
      treated a 59-year-old patient with adenocarcinoma of the uterine cervix,
      endometrium, fallopian tubes, and ovaries. It was difficult to determine whether
      the cancer was a single origin metastatic cancer or a synchronous neoplasm. The
      patient was finally diagnosed with metastatic cancer that originated from the
      uterine cervix by human papillomavirus (HPV) test. Here we report the case and
      briefly review of the medical literature.

PMID- 20041105
TI  - Pregnancy following vulvar squamous cell carcinoma: a report of two cases.
AB  - Pregnancy following squamous cell carcinoma of the vulvar is rare. Its rarity is
      reflected by a paucity of cases reported in the literature. We report two cases
      of pregnancy following diagnosis and treatment for vulvar squamous cell
      carcinoma, and review eleven prior reported cases. In successfully treated vulvar
      cancer subsequent pregnancy is not shown to increase the risk of disease
      recurrence, and there appears to be no deleterious effects during the antenatal
      period. It is possible, when considering prior reports, that prior vulvectomy may
      increase the likelihood of delivery by caesarean section, though modifications in
      the surgical management of vulvar carcinoma may have decreased this risk.

PMID- 20041106
TI  - A favorable maternal and neonatal outcome following chemotherapy with etoposide,
      bleomycin, and cisplatin for management of grade 3 immature teratoma of the
      ovary.
AB  - Ovarian cancer rarely complicates pregnancy. Usually these malignancies consist
      of germ cell tumors. Preserving maternal safety along with favorable neonatal
      outcome is a subject of debate in the management of ovarian cancer during
      pregnancy. In this report, the authors describe a 25-year-old primigravid woman
      who was diagnosed to with an ovarian immature teratoma which was diagnosed at
      13th weeks of pregnancy during a routine sonography. She underwent oophorectomy
      at week 21 of her gestation. Then she received three cycles of BEP regimen
      (bleomycin, etoposide, and cisplatin) during her pregnancy until week 37 of
      gestation. At 36 weeks she delivered a male baby with mild glandular hypospadia
      who was otherwise normal. Management of immature teratoma after the first
      trimester of pregnancy is similar to non-pregnant patients and is safe for both
      the mother and the fetus.

PMID- 20041107
TI  - The evolutionary history of protein domains viewed by species phylogeny.
AB  - BACKGROUND: Protein structural domains are evolutionary units whose relationships
      can be detected over long evolutionary distances. The evolutionary history of
      protein domains, including the origin of protein domains, the identification of
      domain loss, transfer, duplication and combination with other domains to form new
      proteins, and the formation of the entire protein domain repertoire, are of great
      interest. METHODOLOGY/PRINCIPAL FINDINGS: A methodology is presented for
      providing a parsimonious domain history based on gain, loss, vertical and
      horizontal transfer derived from the complete genomic domain assignments of 1015
      organisms across the tree of life. When mapped to species trees the evolutionary
      history of domains and domain combinations is revealed, and the general
      evolutionary trend of domain and combination is analyzed.
      CONCLUSIONS/SIGNIFICANCE: We show that this approach provides a powerful tool to
      study how new proteins and functions emerged and to study such processes as
      horizontal gene transfer among more distant species.

PMID- 20041108
TI  - Yersiniabactin reduces the respiratory oxidative stress response of innate immune
      cells.
AB  - Enterobacteriaceae that contain the High Pathogenicity Island (HPI), which
      encodes the siderophore yersiniabactin, display increased virulence. This
      increased virulence may be explained by the increased iron scavenging of the
      bacteria, which would both enhance bacterial growth and limit the availability of
      iron to cells of the innate immune system, which require iron to catalyze the
      Haber-Weiss reaction that produces hydroxyl radicals. In this study, we show that
      yersiniabactin increases bacterial growth when iron-saturated lactoferrin is the
      main iron source. This suggests that yersiniabactin provides bacteria with
      additional iron from saturated lactoferrin during infection. Furthermore, the
      production of ROS by polymorphonuclear leukocytes, monocytes, and a mouse
      macrophage cell line is blocked by yersiniabactin, as yersiniabactin reduces iron
      availability to the cells. Importantly, iron functions as a catalyst during the
      Haber-Weiss reaction, which generates hydroxyl radicals. While the physiologic
      role of the Haber-Weiss reaction in the production of hydroxyl radicals has been
      controversial, the siderophores yersiniabactin, aerobactin, and deferoxamine and
      the iron-chelator deferiprone also reduce ROS production in activated innate
      immune cells. This suggests that this reaction takes place under physiological
      conditions. Of the tested iron chelators, yersiniabactin was the most effective
      in reducing the ROS production in the tested innate immune cells. The likely
      decreased bacterial killing by innate immune cells resulting from the reduced
      production of hydroxyl radicals may explain why the HPI-containing
      Enterobacteriaceae are more virulent. This model centered on the reduced killing
      capacity of innate immune cells, which is indirectly caused by yersiniabactin, is
      in agreement with the observation that the highly pathogenic group of Yersinia is
      more lethal than the weakly pathogenic and the non-pathogenic group.

PMID- 20041109
TI  - The influence of recombinant production on the immunologic behavior of birch
      pollen isoallergens.
AB  - BACKGROUND: Allergic reactions towards the birch major pollen allergen Bet v 1
      are among the most common causes of spring pollinosis in the temperate climate
      zone of the Northern hemisphere. Natural Bet v 1 is composed of a complex mixture
      of different isoforms. Detailed analysis of recombinant Bet v 1 isoforms revealed
      striking differences in immunologic as well as allergenic properties of the
      molecules, leading to a classification of Bet v 1 isoforms into high, medium, and
      low IgE binding proteins. Especially low IgE binding Bet v 1 isoforms have been
      described as ideal candidates for desensitizing allergic patients with allergen
      specific immunotherapy (SIT). Since diagnosis and therapy of allergic diseases
      are highly dependent on recombinant proteins, continuous improvement of protein
      production is an absolute necessity. METHODOLOGY: Therefore, two different
      methods for recombinant production of a low IgE binding Bet v 1 isoform were
      applied; one based on published protocols, the other by implementing latest
      innovations in protein production. Both batches of Bet v 1.0401 were extensively
      characterized by an array of physicochemical as well as immunological methods to
      compare protein primary structure, purity, quantity, folding, aggregation state,
      thermal stability, and antibody binding capacity. CONCLUSION: The experiments
      demonstrated that IgE antibody binding properties of recombinant isoallergens can
      be significantly influenced by the production method directly affecting possible
      clinical applications of the molecules.

PMID- 20041110
TI  - Neurological soft signs and their relationships to neurocognitive functions: a re
      visit with the structural equation modeling design.
AB  - BACKGROUND: Neurological soft signs and neurocognitive impairments have long been
      considered important features of schizophrenia. Previous correlational studies
      have suggested that there is a significant relationship between neurological soft
      signs and neurocognitive functions. The purpose of the current study was to
      examine the underlying relationships between these two distinct constructs with
      structural equation modeling (SEM). METHODS: 118 patients with schizophrenia and
      160 healthy controls were recruited for the current study. The abridged version
      of the Cambridge Neurological Inventory (CNI) and a set of neurocognitive
      function tests were administered to all participants. SEM was then conducted
      independently in these two samples to examine the relationships between
      neurological soft signs and neurocognitive functions. RESULTS: Both the
      measurement and structural models showed that the models fit well to the data in
      both patients and healthy controls. The structural equations also showed that
      there were modest to moderate associations among neurological soft signs,
      executive attention, verbal memory, and visual memory, while the healthy controls
      showed more limited associations. CONCLUSIONS: The current findings indicate that
      motor coordination, sensory integration, and disinhibition contribute to the
      latent construct of neurological soft signs, whereas the subset of neurocognitive
      function tests contribute to the latent constructs of executive attention, verbal
      memory, and visual memory in the present sample. Greater evidence of neurological
      soft signs is associated with more severe impairment of executive attention and
      memory functions. Clinical and theoretical implications of the model findings are
      discussed.

PMID- 20041111
TI  - Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands.
AB  - BACKGROUND: The MitoChip v2.0 resequencing array is an array-based technique
      allowing for accurate and complete sequencing of the mitochondrial genome. No
      studies have investigated mitochondrial mutation in salivary gland adenoid cystic
      carcinomas. METHODOLOGY: The entire mitochondrial genome of 22 salivary gland
      adenoid cystic carcinomas (ACC) of salivary glands and matched leukocyte DNA was
      sequenced to determine the frequency and distribution of mitochondrial mutations
      in ACC tumors. PRINCIPAL FINDINGS: Seventeen of 22 ACCs (77%) carried
      mitochondrial mutations, ranging in number from 1 to 37 mutations. A
      disproportionate number of mutations occurred in the D-loop. Twelve of 17 tumors
      (70.6%) carried mutations resulting in amino acid changes of translated proteins.
      Nine of 17 tumors (52.9%) with a mutation carried an amino acid changing mutation
      in the nicotinamide adenine dinucleotide dehydrogenase (NADH) complex.
      CONCLUSIONS/SIGNIFICANCE: Mitochondrial mutation is frequent in salivary ACCs.
      The high incidence of amino acid changing mutations implicates alterations in
      aerobic respiration in ACC carcinogenesis. D-loop mutations are of unclear
      significance, but may be associated with alterations in transcription or
      replication.

PMID- 20041112
TI  - Genetic characterization and linkage disequilibrium estimation of a global maize
      collection using SNP markers.
AB  - A newly developed maize Illumina GoldenGate Assay with 1536 SNPs from 582 loci
      was used to genotype a highly diverse global maize collection of 632 inbred lines
      from temperate, tropical, and subtropical public breeding programs. A total of
      1229 informative SNPs and 1749 haplotypes within 327 loci was used to estimate
      the genetic diversity, population structure, and familial relatedness. Population
      structure identified tropical and temperate subgroups, and complex familial
      relationships were identified within the global collection. Linkage
      disequilibrium (LD) was measured overall and within chromosomes, allelic
      frequency groups, subgroups related by geographic origin, and subgroups of
      different sample sizes. The LD decay distance differed among chromosomes and
      ranged between 1 to 10 kb. The LD distance increased with the increase of minor
      allelic frequency (MAF), and with smaller sample sizes, encouraging caution when
      using too few lines in a study. The LD decay distance was much higher in
      temperate than in tropical and subtropical lines, because tropical and
      subtropical lines are more diverse and contain more rare alleles than temperate
      lines. A core set of inbreds was defined based on haplotypes, and 60 lines
      capture 90% of the haplotype diversity of the entire panel. The defined core sets
      and the entire collection can be used widely for different research targets.

PMID- 20041113
TI  - Within-subject variability of interferon-g assay results for tuberculosis and
      boosting effect of tuberculin skin testing: a systematic review.
AB  - BACKGROUND: Variability in interferon-gamma release assays (IGRAs) results for
      tuberculosis has implications for interpretation of results close to the cut
      point, and for defining thresholds for test conversion and reversion. However,
      little is known about the within-subject variability (reproducibility) of IGRAs.
      Several national guidelines recommend a two-step testing procedure (tuberculin
      skin test [TST] followed by IGRA) for the diagnosis of LTBI. However, the effect
      of a preceding TST on subsequent IGRA results has been reported in studies with
      apparently conflicting results. METHODOLOGY/FINDINGS: We conducted a systematic
      review to synthesize evidence on within-subject variability of IGRA results and
      the potential boosting effect of TST. We searched several databases and reviewed
      citations of previous reviews on IGRAs. We included studies using commercial
      IGRAs, in addition to non-commercial versions of the ELISPOT assay. Four studies,
      fulfilling our predefined criteria, examined within-subject variability and 13
      studies evaluated TST effects on subsequent IGRA responses. Meta-analysis was not
      considered appropriate because of heterogeneity in study methods, assays, and
      populations. Although based on limited data, within-subject variability was
      present in all studies but the magnitude varied (16-80%) across studies. A TST
      induced "boosting" of IGRA responses was demonstrated in several studies and
      although more pronounced in IGRA-positive (i.e. sensitized) individuals, also
      occurred in a smaller but not insignificant proportion of IGRA-negative subjects.
      The TST appeared to affect IGRA responses only after 3 days and may apparently
      persist for several months, but evidence for this is weak.
      CONCLUSIONS/SIGNIFICANCE: Although reproducibility data are scarce, significant
      within person IGRA variability has been reported. If confirmed in more studies,
      this has implications for the interpretation of results close to the cut-point
      and for definition of conversions and reversions. Although the effect of TST on
      IGRA results is likely to be inconsequential in IGRA-positive subjects, in IGRA
      negative subjects, the interpretation of results may be confounded by a preceding
      TST if administered more than 3 days prior to an IGRA.

PMID- 20041114
TI  - Influenza in outpatient ILI case-patients in national hospital-based
      surveillance, Bangladesh, 2007-2008.
AB  - BACKGROUND: Recent population-based estimates in a Dhaka low-income community
      suggest that influenza was prevalent among children. To explore the epidemiology
      and seasonality of influenza throughout the country and among all age groups, we
      established nationally representative hospital-based surveillance necessary to
      guide influenza prevention and control efforts. METHODOLOGY/PRINCIPAL FINDINGS:
      We conducted influenza-like illness and severe acute respiratory illness sentinel
      surveillance in 12 hospitals across Bangladesh during May 2007-December 2008. We
      collected specimens from 3,699 patients, 385 (10%) which were influenza positive
      by real time RT-PCR. Among the sample-positive patients, 192 (51%) were type A
      and 188 (49%) were type B. Hemagglutinin subtyping of type A viruses detected 137
      (71%) A/H1 and 55 (29%) A/H3, but no A/H5 or other novel influenza strains. The
      frequency of influenza cases was highest among children aged under 5 years (44%),
      while the proportions of laboratory confirmed cases was highest among
      participants aged 11-15 (18%). We applied kriging, a geo-statistical technique,
      to explore the spatial and temporal spread of influenza and found that, during
      2008, influenza was first identified in large port cities and then gradually
      spread to other parts of the country. We identified a distinct influenza peak
      during the rainy season (May-September). CONCLUSIONS/SIGNIFICANCE: Our
      surveillance data confirms that influenza is prevalent throughout Bangladesh,
      affecting a wide range of ages and causing considerable morbidity and hospital
      care. A unimodal influenza seasonality may allow Bangladesh to time annual
      influenza prevention messages and vaccination campaigns to reduce the national
      influenza burden. To scale-up such national interventions, we need to quantify
      the national rates of influenza and the economic burden associated with this
      disease through further studies.

PMID- 20041115
TI  - Improving the clinical diagnosis of influenza--a comparative analysis of new
      influenza A (H1N1) cases.
AB  - BACKGROUND: The presentation of new influenza A(H1N1) is broad and evolving as it
      continues to affect different geographic locations and populations. To improve
      the accuracy of predicting influenza infection in an outpatient setting, we
      undertook a comparative analysis of H1N1(2009), seasonal influenza, and persons
      with acute respiratory illness (ARI) in an outpatient setting.
      METHODOLOGY/PRINCIPAL FINDINGS: Comparative analyses of one hundred non-matched
      cases each of PCR confirmed H1N1(2009), seasonal influenza, and ARI cases.
      Multivariate analysis was performed to look for predictors of influenza
      infection. Receiver operating characteristic curves were constructed for various
      combinations of clinical and laboratory case definitions. The initial clinical
      and laboratory features of H1N1(2009) and seasonal influenza were similar. Among
      ARI cases, fever, cough, headache, rhinorrhea, the absence of leukocytosis, and a
      normal chest radiograph positively predict for both PCR-confirmed H1N1-2009 and
      seasonal influenza infection. The sensitivity and specificity of current WHO and
      CDC influenza-like illness (ILI) criteria were modest in predicting influenza
      infection. However, the combination of WHO ILI criteria with the absence of
      leukocytosis greatly improved the accuracy of diagnosing H1N1(2009) and seasonal
      influenza (positive LR of 7.8 (95%CI 3.5-17.5) and 9.2 (95%CI 4.1-20.3)
      respectively). CONCLUSIONS/SIGNIFICANCE: The clinical presentation of H1N1(2009)
      infection is largely indistinguishable from that of seasonal influenza. Among
      patients with acute respiratory illness, features such as a temperature greater
      than 38 degrees C, rhinorrhea, a normal chest radiograph, and the absence of
      leukocytosis or significant gastrointestinal symptoms were all positively
      associated with H1N1(2009) and seasonal influenza infection. An enhanced ILI
      criteria that combines both a symptom complex with the absence of leukocytosis on
      testing can improve the accuracy of predicting both seasonal and H1N1-2009
      influenza infection.

PMID- 20041116
TI  - The lipid profile and mortality risk in elderly type 2 diabetic patients: a ten
      year follow-up study (ZODIAC-13).
AB  - BACKGROUND: The precise relationship between the lipid profile and mortality in
      elderly patients with type 2 diabetes mellitus (T2DM) remains unclear. The aim of
      this study was to investigate the relationship between the lipid profile over
      time, and mortality in elderly patients with T2DM. METHODS AND FINDINGS: In 1998,
      881 primary care patients with T2DM aged 60 years and older participated in the
      ZODIAC study, a prospective observational study. The cohort was divided into two
      age categories: 60-75 years and older than 75 years. Updated means of all lipid
      profile indices were calculated after a median follow-up time of 9.8 years. These
      values were used as time dependent covariates in a Cox proportional hazard model.
      The cholesterol-HDL ratio and LDL-cholesterol were positively related to both all
      cause and cardiovascular mortality in the low age group. In contrast, except for
      the triglyceride level, none of the other lipid profile indices were related to
      all-cause mortality in patients aged over 75 years. The mortality risk decreased
      by 17% (95%CI: 5% to 27%) for each 1 mmol/L higher serum level of triglycerides.
      The relationships between the various lipid profile indices and cardiovascular
      mortality were not significant. However, the results were different after
      stratification for diabetes duration. In the subgroup of elderly patients with a
      diabetes duration of 8 years and longer, higher lipids were predictive of
      increased cardiovascular mortality. The main limitation of this study is its
      observational design, which prevents us drawing conclusions about causality.
      CONCLUSION: Although the lipid profile was not predictive in the overall group of
      elderly patients, higher lipids were related to increased cardiovascular
      mortality in patients with diabetes of long duration. In order to make valid
      recommendations concerning lipid-lowering treatment, a randomized controlled
      trial or a meta-analysis concerning this specific population is mandatory.

PMID- 20041117
TI  - Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal
      weight postmenopausal women.
AB  - With age and menopause there is a shift in adipose distribution from gluteo
      femoral to abdominal depots in women. Associated with this redistribution of fat
      are increased risks of type 2 diabetes and cardiovascular disease.
      Glucocorticoids influence body composition, and 11beta-hydroxysteroid
      dehydrogenase type 1 (11betaHSD1) which converts inert cortisone to active
      cortisol is a putative key mediator of metabolic complications in obesity.
      Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central
      obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and
      activity are up-regulated in the older, postmenopausal women compared to young,
      premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal
      weight women were recruited. The participants underwent a urine collection, a
      subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was
      estimated by the serum cortisol response after an oral dose of cortisone. Urinary
      (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol)/tetrahydrocortisone ratios
      were higher in postmenopausal women versus premenopausal women in luteal phase
      (P<0.05), indicating an increased whole-body 11betaHSD1 activity. Postmenopausal
      women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05). Hepatic
      first pass conversion of oral cortisone to cortisol was also increased in
      postmenopausal women versus premenopausal women in follicular phase of the
      menstrual cycle (P<0.01, at 30 min post cortisone ingestion), suggesting higher
      hepatic 11betaHSD1 activity. In conclusion, our results indicate that
      postmenopausal normal weight women have increased 11betaHSD1 activity in adipose
      tissue and liver. This may contribute to metabolic dysfunctions with menopause
      and ageing in women.

PMID- 20041118
TI  - Conserved usage of alternative 5' untranslated exons of the GATA4 gene.
AB  - BACKGROUND: GATA4 is an essential transcription factor required for the
      development and function of multiple organs. Despite this important role, our
      knowledge of how the GATA4 gene is regulated remains limited. To better
      understand this regulation, we characterized the 5' region of the mouse, rat, and
      human GATA4 genes. METHODOLOGY/PRINCIPAL FINDINGS: Using 5' RACE, we identified
      novel transcription start sites in all three species. GATA4 is expressed as
      multiple transcripts with varying 5' ends encoded by alternative untranslated
      first exons. Two of these non-coding first exons are conserved between species:
      exon 1a located 3.5 kb upstream of the GATA4 ATG site in exon 2, and a second
      first exon (exon 1b) located 28 kb further upstream. Expression of both mRNA
      variants was found in all GATA4-expressing organs but with a preference for the
      exon 1a-containing transcript. The exception was the testis where exon 1a- and 1b
      containing transcripts were similarly expressed. In some tissues such as the
      intestine, alternative transcript expression appears to be regionally regulated.
      Polysome analysis suggests that both mRNA variants contribute to GATA4 protein
      synthesis. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that
      the GATA4 gene closely resembles the other GATA family members in terms of gene
      structure where alternative first exon usage appears to be an important mechanism
      for regulating its tissue- and cell-specific expression.

PMID- 20041119
TI  - Enhancement of the influenza A hemagglutinin (HA)-mediated cell-cell fusion and
      virus entry by the viral neuraminidase (NA).
AB  - BACKGROUND: The major role of the neuraminidase (NA) protein of influenza A virus
      is related to its sialidase activity, which disrupts the interaction between the
      envelope hemagglutinin (HA) protein and the sialic acid receptors expressed at
      the surface of infected cells. This enzymatic activity is known to promote the
      release and spread of progeny viral particles following their production by
      infected cells, but a potential role of NA in earlier steps of the viral life
      cycle has never been clearly demonstrated. In this study we have examined the
      impact of NA expression on influenza HA-mediated viral membrane fusion and virion
      infectivity. METHODOLOGY/PRINCIPAL FINDINGS: The role of NA in the early stages
      of influenza virus replication was examined using a cell-cell fusion assay that
      mimics HA-mediated membrane fusion, and a virion infectivity assay using HIV
      based pseudoparticles expressing influenza HA and/or NA proteins. In the cell
      cell fusion assay, which bypasses the endocytocytosis step that is characteristic
      of influenza virus entry, we found that in proper HA maturation conditions, NA
      clearly enhanced fusion in a dose-dependent manner. Similarly, expression of NA
      at the surface of pseudoparticles significantly enhanced virion infectivity.
      Further experiments using exogenous soluble NA revealed that the most likely
      mechanism for enhancement of fusion and infectivity by NA was related to
      desialylation of virion-expressed HA. CONCLUSION/SIGNIFICANCE: The NA protein of
      influenza A virus is not only required for virion release and spread but also
      plays a critical role in virion infectivity and HA-mediated membrane fusion.

PMID- 20041120
TI  - The global spread of hepatitis C virus 1a and 1b: a phylodynamic and
      phylogeographic analysis.
AB  - BACKGROUND: Hepatitis C virus (HCV) is estimated to affect 130-180 million people
      worldwide. Although its origin is unknown, patterns of viral diversity suggest
      that HCV genotype 1 probably originated from West Africa. Previous attempts to
      estimate the spatiotemporal parameters of the virus, both globally and
      regionally, have suggested that epidemic HCV transmission began in 1900 and grew
      steadily until the late 1980s. However, epidemiological data suggest that the
      expansion of HCV may have occurred after the Second World War. The aim of our
      study was to elucidate the timescale and route of the global spread of HCV.
      METHODS AND FINDINGS: We show that the rarely sequenced HCV region (E2P7NS2) is
      more informative for molecular epidemiology studies than the more commonly used
      NS5B region. We applied phylodynamic methods to a substantial set of new E2P7NS2
      and NS5B sequences, together with all available global HCV sequences with
      information in both of these genomic regions, in order to estimate the timescale
      and nature of the global expansion of the most prevalent HCV subtypes, 1a and 1b.
      We showed that transmission of subtypes 1a and 1b "exploded" between 1940 and
      1980, with the spread of 1b preceding that of 1a by at least 16 y (95% confidence
      interval 15-17). Phylogeographic analysis of all available NS5B sequences
      suggests that HCV subtypes 1a and 1b disseminated from the developed world to the
      developing countries. CONCLUSIONS: The evolutionary rate of HCV appears faster
      than previously suggested. The global spread of HCV coincided with the widespread
      use of transfused blood and blood products and with the expansion of intravenous
      drug use but slowed prior to the wide implementation of anti-HCV screening.
      Differences in the transmission routes associated with subtypes 1a and 1b provide
      an explanation of the relatively earlier expansion of 1b. Our data show that the
      most plausible route of the HCV dispersal was from developed countries to the
      developing world. Please see later in the article for the Editors' Summary.

PMID- 20041121
TI  - School variation in asthma: compositional or contextual?
AB  - BACKGROUND: Childhood asthma prevalence and morbidity have been shown to vary by
      neighborhood. Less is known about between-school variation in asthma prevalence
      and whether it exists beyond what one might expect due to students at higher risk
      of asthma clustering within different schools. Our objective was to determine
      whether between-school variation in asthma prevalence exists and if so, if it is
      related to the differential distribution of individual risk factors for and
      correlates of asthma or to contextual influences of schools. METHODS: Cross
      sectional analysis of 16,640 teens in grades 7-12 in Wave 1 (data collected in
      1994-5) of the National Longitudinal Study of Adolescent Health. Outcome was
      current diagnosis of asthma as reported by respondents' parents. Two-level random
      effects models were used to assess the contribution of schools to the variance in
      asthma prevalence before and after controlling for individual attributes.
      RESULTS: The highest quartile schools had mean asthma prevalence of 21.9%
      compared to the lowest quartile schools with mean asthma prevalence of 7.1%. In
      our null model, the school contributed significantly to the variance in asthma
      (sigma(u0)(2) = 0.27, CI: 0.20, 0.35). Controlling for individual, school and
      neighborhood attributes reduced the between-school variance modestly
      (sigma(u0)(2) = 0.19 CI: 0.13-0.29). CONCLUSION: Significant between-school
      variation in current asthma prevalence exists even after controlling for the
      individual, school and neighborhood factors. This provides evidence for school
      level contextual influences on asthma. Further research is needed to determine
      potential mechanisms through which schools may influence asthma outcomes.

PMID- 20041122
TI  - Steered molecular dynamics simulations reveal the likelier dissociation pathway
      of imatinib from its targeting kinases c-Kit and Abl.
AB  - Development of small molecular kinase inhibitors has recently been the central
      focus in drug discovery. And type II kinase inhibitors that target inactive
      conformation of kinases have attracted particular attention since their potency
      and selectivity are thought to be easier to achieve compared with their
      counterpart type I inhibitors that target active conformation of kinases.
      Although mechanisms underlying the interactions between type II inhibitors and
      their targeting kinases have been widely studied, there are still some
      challenging problems, for example, how type II inhibitors associate with or
      dissociate from their targeting kinases. In this investigation, steered molecular
      dynamics simulations have been carried out to explore the possible dissociation
      pathways of typical type II inhibitor imatinib from its targeting protein kinases
      c-Kit and Abl. The simulation results indicate that the most favorable pathway
      for imatinib dissociation corresponds to the ATP-channel rather than the
      relatively wider allosteric-pocket-channel, which is mainly due to the different
      van der Waals interaction that the ligand suffers during dissociation.
      Nevertheless, the direct reason comes from the fact that the residues composing
      the ATP-channel are more flexible than that forming the allosteric-pocket
      channel. The present investigation suggests that a bulky hydrophobic head is
      unfavorable, but a large polar tail is allowed for a potent type II inhibitor.
      The information obtained here can be used to direct the discovery of type II
      kinase inhibitors.

PMID- 20041123
TI  - AutoEPG: software for the analysis of electrical activity in the microcircuit
      underpinning feeding behaviour of Caenorhabditis elegans.
AB  - BACKGROUND: The pharyngeal microcircuit of the nematode Caenorhabditis elegans
      serves as a model for analysing neural network activity and is amenable to
      electrophysiological recording techniques. One such technique is the
      electropharyngeogram (EPG) which has provided insight into the genetic basis of
      feeding behaviour, neurotransmission and muscle excitability. However, the
      detailed manual analysis of the digital recordings necessary to identify subtle
      differences in activity that reflect modulatory changes within the underlying
      network is time consuming and low throughput. To address this we have developed
      an automated system for the high-throughput and discrete analysis of EPG
      recordings (AutoEPG). METHODOLOGY/PRINCIPAL FINDINGS: AutoEPG employs a tailor
      made signal processing algorithm that automatically detects different features of
      the EPG signal including those that report on the relaxation and contraction of
      the muscle and neuronal activity. Manual verification of the detection algorithm
      has demonstrated AutoEPG is capable of very high levels of accuracy. We have
      further validated the software by analysing existing mutant strains with known
      pharyngeal phenotypes detectable by the EPG. In doing so, we have more precisely
      defined an evolutionarily conserved role for the calcium-dependent potassium
      channel, SLO-1, in modulating the rhythmic activity of neural networks.
      CONCLUSIONS/SIGNIFICANCE: AutoEPG enables the consistent analysis of EPG
      recordings, significantly increases analysis throughput and allows the robust
      identification of subtle changes in the electrical activity of the pharyngeal
      nervous system. It is anticipated that AutoEPG will further add to the
      experimental tractability of the C. elegans pharynx as a model neural circuit.

PMID- 20041124
TI  - A conceptual mathematical model of the dynamic self-organisation of distinct
      cellular organelles.
AB  - Formation, degradation and renewal of cellular organelles is a dynamic process
      based on permanent budding, fusion and inter-organelle traffic of vesicles. These
      processes include many regulatory proteins such as SNAREs, Rabs and coats. Given
      this complex machinery, a controversially debated issue is the definition of a
      minimal set of generic mechanisms necessary to enable the self-organization of
      organelles differing in number, size and chemical composition. We present a
      conceptual mathematical model of dynamic organelle formation based on interacting
      vesicles which carry different types of fusogenic proteins (FP) playing the role
      of characteristic marker proteins. Our simulations (ODEs) show that a de novo
      formation of non-identical organelles, each accumulating a different type of FP,
      requires a certain degree of disproportionation of FPs during budding. More
      importantly however, the fusion kinetics must indispensably exhibit positive
      cooperativity among these FPs, particularly for the formation of larger
      organelles. We compared different types of cooperativity: sequential alignment of
      corresponding FPs on opposite vesicle/organelles during fusion and pre-formation
      of FP-aggregates (equivalent, e.g., to SNARE clusters) prior to fusion described
      by Hill kinetics. This showed that the average organelle size in the system is
      much more sensitive to the disproportionation strength of FPs during budding if
      the vesicular transport system gets along with a fusion mechanism based on
      sequential alignments of FPs. Therefore, pre-formation of FP aggregates within
      the membranes prior to fusion introduce robustness with respect to organelle
      size. Our findings provide a plausible explanation for the evolution of a
      relatively large number of molecules to confer specificity on the fusion
      machinery compared to the relatively small number involved in the budding
      process. Moreover, we could speculate that a specific cooperativity which may be
      described by Hill kinetics (aggregates or Rab/SNARE complex formation) is
      suitable if maturation/identity switching of organelles play a role
      (bistability).

PMID- 20041125
TI  - Contrasting population structures of the genes encoding ten leading vaccine
      candidate antigens of the human malaria parasite, Plasmodium falciparum.
AB  - The extensive diversity of Plasmodium falciparum antigens is a major obstacle to
      a broadly effective malaria vaccine but population genetics has rarely been used
      to guide vaccine design. We have completed a meta-population genetic analysis of
      the genes encoding ten leading P. falciparum vaccine antigens, including the pre
      erythrocytic antigens csp, trap, lsa1 and glurp; the merozoite antigens eba175,
      ama1, msp's 1, 3 and 4, and the gametocyte antigen pfs48/45. A total of 4553
      antigen sequences were assembled from published data and we estimated the range
      and distribution of diversity worldwide using traditional population genetics,
      Bayesian clustering and network analysis. Although a large number of distinct
      haplotypes were identified for each antigen, they were organized into a limited
      number of discrete subgroups. While the non-merozoite antigens showed
      geographically variable levels of diversity and geographic restriction of
      specific subgroups, the merozoite antigens had high levels of diversity globally,
      and a worldwide distribution of each subgroup. This shows that the diversity of
      the non-merozoite antigens is organized by physical or other location-specific
      barriers to gene flow and that of merozoite antigens by features intrinsic to all
      populations, one important possibility being the immune response of the human
      host. We also show that current malaria vaccine formulations are based upon low
      prevalence haplotypes from a single subgroup and thus may represent only a small
      proportion of the global parasite population. This study demonstrates significant
      contrasts in the population structure of P. falciparum vaccine candidates that
      are consistent with the merozoite antigens being under stronger balancing
      selection than non-merozoite antigens and suggesting that unique approaches to
      vaccine design will be required. The results of this study also provide a
      realistic framework for the diversity of these antigens to be incorporated into
      the design of next-generation malaria vaccines.

PMID- 20041126
TI  - Regulation of energy stores and feeding by neuronal and peripheral CREB activity
      in Drosophila.
AB  - The cAMP-responsive transcription factor CREB functions in adipose tissue and
      liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has
      a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully
      understood. Using tissue-specific expression of a dominant-negative form of CREB
      (DN-CREB), we have examined the effect of blocking CREB activity in neurons and
      in the fat body, the primary energy storage depot with functions of adipose
      tissue and the liver in flies, on energy balance, stress resistance and feeding
      behavior. We found that disruption of CREB function in neurons reduced glycogen
      and lipid stores and increased sensitivity to starvation. Expression of DN-CREB
      in the fat body also reduced glycogen levels, while it did not affect starvation
      sensitivity, presumably due to increased lipid levels in these flies.
      Interestingly, blocking CREB activity in the fat body increased food intake.
      These flies did not show a significant change in overall body size, suggesting
      that disruption of CREB activity in the fat body caused an obese-like phenotype.
      Using a transgenic CRE-luciferase reporter, we further demonstrated that
      disruption of the adipokinetic hormone receptor, which is functionally related to
      mammalian glucagon and beta-adrenergic signaling, in the fat body reduced CRE
      mediated transcription in flies. This study demonstrates that CREB activity in
      either neuronal or peripheral tissues regulates energy balance in Drosophila, and
      that the key signaling pathway regulating CREB activity in peripheral tissue is
      evolutionarily conserved.

PMID- 20041127
TI  - Structural basis of chemokine sequestration by a tick chemokine binding protein:
      the crystal structure of the complex between Evasin-1 and CCL3.
AB  - BACKGROUND: Chemokines are a subset of cytokines responsible for controlling the
      cellular migration of inflammatory cells through interaction with seven
      transmembrane G protein-coupled receptors. The blocking of a chemokine-receptor
      interaction results in a reduced inflammatory response, and represents a possible
      anti-inflammatory strategy, a strategy that is already employed by some virus and
      parasites. Anti-chemokine activity has been described in the extracts of tick
      salivary glands, and we have recently described the cloning and characterization
      of such chemokine binding proteins from the salivary glands, which we have named
      Evasins. METHODOLOGY/PRINCIPAL FINDINGS: We have solved the structure of Evasin
      1, a very small and highly selective chemokine-binding protein, by x-ray
      crystallography and report that the structure is novel, with no obvious
      similarity to the previously described structures of viral chemokine binding
      proteins. Moreover it does not possess a known fold. We have also solved the
      structure of the complex of Evasin-1 and its high affinity ligand, CCL3. The
      complex is a 1:1 heterodimer in which the N-terminal region of CCL3 forms
      numerous contacts with Evasin-1, including prominent pi-pi interactions between
      residues Trp89 and Phe14 of the binding protein and Phe29 and Phe13 of the
      chemokine. CONCLUSIONS/SIGNIFICANCE: However, these interactions do not appear to
      be crucial for the selectivity of the binding protein, since these residues are
      found in CCL5, which is not a ligand for Evasin-1. The selectivity of the
      interaction would appear to lie in the N-terminal residues of the chemokine,
      which form the "address" whereas the hydrophobic interactions in the rest of the
      complex would serve primarily to stabilize the complex. A thorough understanding
      of the binding mode of this small protein, and its other family members, could be
      very informative in the design of potent neutralizing molecules of pro
      inflammatory mediators of the immune system, such as chemokines.

PMID- 20041128
TI  - Investigating the effects of statins on cellular lipid metabolism using a yeast
      expression system.
AB  - In humans, defects in lipid metabolism are associated with a number of severe
      diseases such as atherosclerosis, obesity and type II diabetes.
      Hypercholesterolemia is a primary risk factor for coronary artery disease, the
      major cause of premature deaths in developed countries. Statins are inhibitors of
      3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol
      synthesis pathway. Since yeast Saccharomyces cerevisiae harbours many
      counterparts of mammalian enzymes involved in lipid-synthesizing pathways,
      conclusions drawn from research with this single cell eukaryotic organism can be
      readily applied to higher eukaryotes. Using a yeast strain with deletions of both
      HMG1 and HMG2 genes (i.e. completely devoid of HMGR activity) with introduced
      wild-type or mutant form of human HMGR (hHMGR) gene we investigated the effects
      of statins on the lipid metabolism of the cell. The relative quantification of
      mRNA demonstrated a different effect of simvastatin on the expression of the wild
      type and mutated hHMGR gene. GC/MS analyses showed a significant decrease of
      sterols and enhanced conversion of squalene and sterol precursors into
      ergosterol. This was accompanied by the mobilization of ergosterol precursors
      localized in lipid particles in the form of steryl esters visualized by confocal
      microscopy. Changes in the level of ergosterol and its precursors in cells
      treated with simvastatin depend on the mutation in the hHMGR gene. HPLC/MS
      analyses indicated a reduced level of phospholipids not connected with the
      mevalonic acid pathway. We detected two significant phenomena. First, cells
      treated with simvastatin develop an adaptive response compensating the lower
      activity of HMGR. This includes enhanced conversion of sterol precursors into
      ergosterol, mobilization of steryl esters and increased expression of the hHMGR
      gene. Second, statins cause a substantial drop in the level of
      glycerophospholipids.

PMID- 20041130
TI  - When salpingectomy is not salpingectomy-ipsilateral recurrence of tubal
      pregnancy.
AB  - Theoretically, total salpingectomy eliminates the risk of an ipsilateral tubal
      pregnancy. However, total salpingectomy is difficult to achieve using endoloops
      alone. We describe a situation where this resulted in an ipsilateral recurrence
      of tubal pregnancy which required emergency intervention and removal of the tubal
      remnants.

PMID- 20041131
TI  - Mohs micrographic surgery for dermatofibrosarcoma protuberans of the vulva.
AB  - Introduction. Dermatofibrosarcoma Protuberans (DFSP) is a rare cutaneous tumour
      of low/intermediate malignant potential, which occasionally arises on the vulva.
      Historically, the treatment has been wide local excision (WLE). Mohs micrographic
      surgery (MMS) is now recommended to ensure precise margin control. MMS to treat
      DFSP of the trunk and extremities is well documented. However, no report to date
      has described its use in vulval DFSP. Case History. A 39 year old woman presented
      with a longstanding nodule in the left labium majus. Histology after surgical
      removal showed an incompletely excised DFSP. MMS was undertaken with primary
      closure of the defect. Three years following treatment there is no evidence of
      recurrence. Discussion. The local recurrence rate of DFSP after WLE ranges from 0
      75%. Finger-like projections from DFSP into surrounding tissue often results in
      incomplete excision. Representative vertical sections used in WLE assess less
      than 1% of the total tumour margin. MMS uses systematic horizontal sectioning.
      100% of the tumour margin is microscopically examined. MMS is now advocated to
      ensure precise margin control.

PMID- 20041129
TI  - Critical role of arcuate Y4 receptors and the melanocortin system in pancreatic
      polypeptide-induced reduction in food intake in mice.
AB  - BACKGROUND: Pancreatic polypeptide (PP) is a potent anti-obesity agent known to
      inhibit food intake in the absence of nausea, but the mechanism behind this
      process is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that in
      response to i.p. injection of PP in wild type but not in Y4 receptor knockout
      mice, immunostaining for the neuronal activation marker c-Fos is induced
      specifically in neurons of the nucleus tractus solitarius and the area postrema
      in the brainstem, notably in cells also showing immunostaining for tyrosine
      hydroxylase. Importantly, strong c-Fos activation is also detected in the arcuate
      nucleus of the hypothalamus (ARC), particularly in neurons that co-express alpha
      melanocyte stimulating hormone (alpha-MSH), the anorexigenic product of the
      proopiomelanocortin (POMC) gene. Interestingly, other hypothalamic regions such
      as the paraventricular nucleus, the ventromedial nucleus and the lateral
      hypothalamic area also show c-Fos induction after PP injection. In addition to c
      Fos activation, PP injection up-regulates POMC mRNA expression in the ARC as
      detected by in situ hybridization. These effects are a direct consequence of
      local Y4 signaling, since hypothalamus-specific conditional Y4 receptor knockout
      abolishes PP-induced ARC c-Fos activation and blocks the PP-induced increase in
      POMC mRNA expression. Additionally, the hypophagic effect of i.p. PP seen in wild
      type mice is completely absent in melanocortin 4 receptor knockout mice.
      CONCLUSIONS/SIGNIFICANCE: Taken together, these findings show that PP reduces
      food intake predominantly via stimulation of the anorexigenic alpha-MSH signaling
      pathway, and that this effect is mediated by direct action on local Y4 receptors
      within the ARC, highlighting a potential novel avenue for the treatment of
      obesity.

PMID- 20041132
TI  - Intra-Abdominal Bleeding during Pregnancy, Preterm Delivery, and Placental Polyp
      in a Long-Term Survivor of Neuroblastoma: A Case Report.
AB  - Background. There are few reports of pregnancies in long-term survivors of pelvic
      neuroblastoma. Case. A 30-year-old Japanese woman with a history of pelvic
      neuroblastoma in her childhood, which was treated with surgical resection,
      chemotherapy, and radiation. Her pregnancy continued with conservative
      management, but she delivered a 510 g female infant at 23 weeks of gestation due
      to sudden onset of labor pain. She also had a placental polyp and developed
      massive postpartum bleeding. Conclusion. Cancer treatment, especially radiation
      therapy, in childhood may cause adverse outcomes during pregnancy in long-term
      survivors of neuroblastoma.

PMID- 20041133
TI  - Expression of Semaphorin 3F and Its Receptors in Epithelial Ovarian Cancer,
      Fallopian Tubes, and Secondary Mullerian Tissues.
AB  - While semaphorins and their receptors appear to play a role in tumor
      carcinogenesis, little is known about the role of semaphorin 3F (S3F) in
      epithelial ovarian cancer (EOC) development. Therefore, we sought to determine
      the clinical relationship between S3F and its receptors, neuropilin-2 (NP-2) and
      neuropilin-1 (NP-1) with EOC progression. We analyzed the immunohistological
      expression of S3F, NP-2, and NP-1 in clinical specimens of normal ovaries (N),
      benign cystadenomas (Cy), well-differentiated adenocarcinomas (WD), poorly
      differentiated adenocarcinomas (PD), inclusion cysts (IC), paraovarian cysts
      (PC), and fallopian tubes (FT). Tissue sections were evaluated for staining
      intensity and percentage of immunoreactive epithelia. We found that expression of
      S3F and NP-2 decreased while NP-1 expression increased with EOC progression.
      Interestingly, we also found elevated expression of S3F, NP-2, and NP-1 in
      epithelia of ICs, PCs, and FT. Our findings indicate that loss or deregulation of
      semaphorin signaling may play an important role in EOC development.

PMID- 20041134
TI  - Elevated middle cerebral artery peak systolic velocity in a nonanemic fetus with
      alpha-thalassemia trait.
AB  - Background. Elevated middle cerebral artery peak systolic velocity (MCA-PSV) has
      been reported in nonanemic fetuses following fetal transfusion, and has been
      attributed to a major population of red blood cells (RBCs) with an adult mean
      corpuscular volume (MCV) in the fetal circulation. Reported here is an analogous
      case of elevated MCA-PSV with a normal fetal hematocrit and relative fetal
      microcytosis due to fetal alpha-thalassemia trait. Case. Ultrasound findings
      concerning for early hydrops prompted measurement of MCA-PSV, which was elevated.
      Cordocentesis revealed fetal microcytosis with a normal hematocrit which proved
      to be due to fetal alpha-thalassemia trait inherited from the mother. Conclusion.
      This case provides another example of elevated MCA-PSV with normal hematocrit and
      microcytosis, here due to fetal alpha-thalassemia trait. This finding provides
      support for the observation that MCA-PSV may be influenced by hematological
      indices other than the fetal hematocrit.

PMID- 20041135
TI  - Reduced pain and inflammation in juvenile and adult rats fed a ketogenic diet.
AB  - The ketogenic diet is a high-fat, low-carbohydrate regimen that forces ketone
      based rather than glucose-based cellular metabolism. Clinically, maintenance on a
      ketogenic diet has been proven effective in treating pediatric epilepsy and type
      II diabetes, and recent basic research provides evidence that ketogenic
      strategies offer promise in reducing brain injury. Cellular mechanisms
      hypothesized to be mobilized by ketone metabolism and underlying the success of
      ketogenic diet therapy, such as reduced reactive oxygen species and increased
      central adenosine, suggest that the ketolytic metabolism induced by the diet
      could reduce pain and inflammation. To test the effects of a ketone-based
      metabolism on pain and inflammation directly, we fed juvenile and adult rats a
      control diet (standard rodent chow) or ketogenic diet (79% fat) ad libitum for 3
      4 weeks. We then quantified hindpaw thermal nociception as a pain measure and
      complete Freund's adjuvant-induced local hindpaw swelling and plasma
      extravasation (fluid movement from the vasculature) as inflammation measures.
      Independent of age, maintenance on a ketogenic diet reduced the peripheral
      inflammatory response significantly as measured by paw swelling and plasma
      extravasation. The ketogenic diet also induced significant thermal hypoalgesia
      independent of age, shown by increased hindpaw withdrawal latency in the hotplate
      nociception test. Anti-inflammatory and hypoalgesic diet effects were generally
      more robust in juveniles. The ketogenic diet elevated plasma ketones similarly in
      both age groups, but caused slowed body growth only in juveniles. These data
      suggest that applying a ketogenic diet or exploiting cellular mechanisms
      associated with ketone-based metabolism offers new therapeutic opportunities for
      controlling pain and peripheral inflammation, and that such a metabolic strategy
      may offer significant benefits for children and adults.

PMID- 20041136
TI  - A Pleistocene clone of Palmer's oak persisting in Southern California.
AB  - BACKGROUND: The distribution of Palmer's oak (Quercus palmeri Engelm.) includes
      numerous isolated populations that are presumably relicts of a formerly larger
      range that has contracted due to spreading aridity following the end of the
      Pleistocene. PRINCIPAL FINDINGS: We investigated a recently discovered disjunct
      population of Palmer's oak in the Jurupa Mountains of Riverside County,
      California. Patterns of allozyme polymorphism, morphological homogeneity,
      widespread fruit abortion, and evidence of fire resprouting all strongly support
      the hypothesis that the population is a single clone. The size of the clone and
      estimates of annual growth from multiple populations lead us to conclude that the
      clone is in excess of 13,000 years old. CONCLUSIONS: The ancient age of the clone
      implies it originated during the Pleistocene and is a relict of a vanished
      vegetation community. Range contraction after climate change best explains the
      modern disjunct distribution of Q. palmeri and perhaps other plants in
      California.

PMID- 20041137
TI  - Explaining the imperfection of the molecular clock of hominid mitochondria.
AB  - The molecular clock of mitochondrial DNA has been extensively used to date
      various genetic events. However, its substitution rate among humans appears to be
      higher than rates inferred from human-chimpanzee comparisons, limiting the
      potential of interspecies clock calibrations for intraspecific dating. It is not
      well understood how and why the substitution rate accelerates. We have analyzed a
      phylogenetic tree of 3057 publicly available human mitochondrial DNA coding
      region sequences for changes in the ratios of mutations belonging to different
      functional classes. The proportion of non-synonymous and RNA genes substitutions
      has reduced over hundreds of thousands of years. The highest mutation ratios
      corresponding to fast acceleration in the apparent substitution rate of the
      coding sequence have occurred after the end of the Last Ice Age. We recalibrate
      the molecular clock of human mtDNA as 7990 years per synonymous mutation over the
      mitochondrial genome. However, the distribution of substitutions at synonymous
      sites in human data significantly departs from a model assuming a single rate
      parameter and implies at least 3 different subclasses of sites. Neutral model
      with 3 synonymous substitution rates can explain most, if not all, of the
      apparent molecular clock difference between the intra- and interspecies levels.
      Our findings imply the sluggishness of purifying selection in removing the
      slightly deleterious mutations from the human as well as the Neandertal and
      chimpanzee populations. However, for humans, the weakness of purifying selection
      has been further exacerbated by the population expansions associated with the out
      of Africa migration and the end of the Last Ice Age.

PMID- 20041138
TI  - Differential effects of thiazolidinediones on adipocyte growth and recruitment in
      Zucker fatty rats.
AB  - BACKGROUND: Adipose tissue grows by two mechanisms: hyperplasia (cell number
      increase) and hypertrophy (cell size increase). Thiazolidinediones are insulin
      sensitizing peroxisome proliferator-activated receptor gamma agonists that are
      known to affect the morphology of adipose tissue. METHODOLOGY: In this study,
      adipose cell-size probability distributions were measured in six Zucker fa/fa
      rats over a period of 24 days, from four weeks of age, using micro-biopsies to
      obtain subcutaneous (inguinal) fat tissue from the animals. Three of the rats
      were gavaged daily with rosiglitazone, a thiazolidinedione, and three served as
      controls. These longitudinal probability distributions were analyzed to obtain
      the rate of increase in cell-size diameter in rosiglitazone-treated animals, and
      the hyperplasia induced by treatment quantitatively. CONCLUSIONS: We found that
      treatment leads to hypertrophy that leads to an approximately linear rate of cell
      diameter increase (2 m/day), and that the hyperplasia evident in treated animals
      occurs largely within the first eight days of treatment. The availability of
      additional lipid storage due to treatment may alleviate lipotoxicity and thereby
      promote insulin sensitivity. The hypothesis that a TZD regimen involving repeated
      treatments of limited duration may suffice for improvements in insulin
      sensitivity merits further investigation.

PMID- 20041139
TI  - An experiment on prediction markets in science.
AB  - Prediction markets are powerful forecasting tools. They have the potential to
      aggregate private information, to generate and disseminate a consensus among the
      market participants, and to provide incentives for information acquisition. These
      market functionalities can be very valuable for scientific research. Here, we
      report an experiment that examines the compatibility of prediction markets with
      the current practice of scientific publication. We investigated three settings.
      In the first setting, different pieces of information were disclosed to the
      public during the experiment. In the second setting, participants received
      private information. In the third setting, each piece of information was private
      at first, but was subsequently disclosed to the public. An automated, subsidizing
      market maker provided additional incentives for trading and mitigated liquidity
      problems. We find that the third setting combines the advantages of the first and
      second settings. Market performance was as good as in the setting with public
      information, and better than in the setting with private information. In contrast
      to the first setting, participants could benefit from information advantages.
      Thus the publication of information does not detract from the functionality of
      prediction markets. We conclude that for integrating prediction markets into the
      practice of scientific research it is of advantage to use subsidizing market
      makers, and to keep markets aligned with current publication practice.

PMID- 20041140
TI  - Ambulatory-based standardized therapy for multi-drug resistant tuberculosis:
      experience from Nepal, 2005-2006.
AB  - OBJECTIVE: The aim of this study was to describe treatment outcomes for multi
      drug resistant tuberculosis (MDR-TB) outpatients on a standardized regimen in
      Nepal. METHODOLOGY: Data on pulmonary MDR-TB patients enrolled for treatment in
      the Green Light Committee-approved National Programme between 15 September 2005
      and 15 September 2006 were studied. Standardized regimen was used (8Z-Km-Ofx-Eto
      Cs/16Z-Ofx-Eto-Cs) for a maximum of 32 months and follow-up was by smear and
      culture. Drug susceptibility testing (DST) results were not used to modify the
      treatment regimen. MDR-TB therapy was delivered in outpatient facilities for the
      whole course of treatment. Multivariable analysis was used to explain
      bacteriological cure as a function of sex, age, initial body weight, history of
      previous treatment and the region of report. PRINCIPAL FINDINGS: In the first 12
      months, 175 laboratory-confirmed MDR-TB cases (62% males) had outcomes reported.
      Most cases had failed a Category 2 first-line regimen (87%) or a Category 1
      regimen (6%), 2% were previously untreated contacts of MDR-TB cases and 5% were
      unspecified. Cure was reported among 70% of patients (range 38%-93% by Region),
      8% died, 5% failed treatment, and 17% defaulted. Unfavorable outcomes were not
      correlated to the number of resistant drugs at baseline DST. Cases who died had a
      lower mean body weight than those surviving (40.3 kg vs 47.2 kg, p<0.05). Default
      was significantly higher in two regions [Eastern OR = 6.2; 95%CL2.0-18.9; Far
      West OR = 5.0; 95%CL1.0-24.3]. At logistic regression, cure was inversely
      associated with body weight <36 kg [Adj.OR = 0.1; 95%CL0.0-0.3; ref. 55-75 kg]
      and treatment in the Eastern region [Adj.OR = 0.1; 95%CL0.0-0.4; ref. Central
      region]. CONCLUSIONS: The implementation of an ambulatory-based treatment
      programme for MDR-TB based on a fully standardized regimen can yield high cure
      rates even in resource-limited settings. The determinants of unfavorable outcome
      should be investigated thoroughly to maximize likelihood of successful treatment.

PMID- 20041141
TI  - Advancing paternal age is associated with deficits in social and exploratory
      behaviors in the offspring: a mouse model.
AB  - BACKGROUND: Accumulating evidence from epidemiological research has demonstrated
      an association between advanced paternal age and risk for several psychiatric
      disorders including autism, schizophrenia and early-onset bipolar disorder. In
      order to establish causality, this study used an animal model to investigate the
      effects of advanced paternal age on behavioural deficits in the offspring.
      METHODS: C57BL/6J offspring (n = 12 per group) were bred from fathers of two
      different ages, 2 months (young) and 10 months (old), and mothers aged 2 months
      (n = 6 breeding pairs per group). Social and exploratory behaviors were examined
      in the offspring. PRINCIPAL FINDINGS: The offspring of older fathers were found
      to engage in significantly less social (p = 0.02) and exploratory (p = 0.02)
      behaviors than the offspring of younger fathers. There were no significant
      differences in measures of motor activity. CONCLUSIONS: Given the well-controlled
      nature of this study, this provides the strongest evidence for deleterious
      effects of advancing paternal age on social and exploratory behavior. De-novo
      chromosomal changes and/or inherited epigenetic changes are the most plausible
      explanatory factors.

PMID- 20041142
TI  - In vivo dynamical interactions between CD4 Tregs, CD8 Tregs and CD4+ CD25- cells
      in mice.
AB  - BACKGROUND: Regulatory T cells (Tregs) were shown to be central in maintaining
      immunological homeostasis and preventing the development of autoimmune diseases.
      Several subsets of Tregs have been identified to date; however, the dynamics of
      the interactions between these subsets, and their implications on their
      regulatory functions are yet to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: We
      employed a combination of mathematical modeling and frequent in vivo measurements
      of several T cell subsets. Healthy BALB/c mice received a single injection of
      either hCDR1--a tolerogenic peptide previously shown to induce Tregs, a control
      peptide or vehicle alone, and were monitored for 16 days. During this period,
      splenocytes from the treated mice were analyzed for the levels of CD4, CD25, CD8,
      CD28 and Foxp3. The collected data were then fitted to mathematical models, in
      order to test competing hypotheses regarding the interactions between the
      followed T cell subsets. In all 3 treatment groups, a significant, lasting, non
      random perturbation of the immune system could be observed. Our analysis
      predicted the emergence of functional CD4 Tregs based on inverse oscillations of
      the latter and CD4(+)CD25(-) cells. Furthermore, CD4 Tregs seemed to require a
      sufficiently high level of CD8 Tregs in order to become functional, while
      conversion was unlikely to be their major source. Our results indicated in
      addition that Foxp3 is not a sufficient marker for regulatory activity.
      CONCLUSIONS/SIGNIFICANCE: In this work, we unraveled the dynamics of the
      interplay between CD4, CD8 Tregs and effector T cells, using, for the first time,
      a mathematical-mechanistic perspective in the analysis of Treg kinetics.
      Furthermore, the results obtained from this interdisciplinary approach supported
      the notion that CD4 Tregs need to interact with CD8 Tregs in order to become
      functional. Finally, we generated predictions regarding the time-dependent
      function of Tregs, which can be further tested empirically in future work.

PMID- 20041143
TI  - Denial of risk behavior does not exclude asymptomatic anorectal sexually
      transmitted infection in HIV-infected men.
AB  - BACKGROUND: The Centers for Disease Control recommend screening for asymptomatic
      sexually transmitted infection (STI) among HIV-infected men when there is self
      report of unprotected anal-receptive exposure. The study goals were: (1) to
      estimate the validity and usefulness for screening policies of self-reported
      unprotected anal-receptive exposure as a risk indicator for asymptomatic
      anorectal infection with Neisseria gonorrhoeae (GC) and/or Chlamydia trachomatis
      (CT). (2) to estimate the number of infections that would be missed if anal
      diagnostic assays were not performed among patients who denied unprotected
      anorectal exposure in the preceding month. METHODS AND FINDINGS: Retrospective
      analysis in HIV primary care and high resolution anoscopy (HRA) clinics. HIV
      infected adult men were screened for self-reported exposure during the previous
      month at all primary care and HRA appointments. Four sub-cohorts were defined
      based on microbiology methodology (GC culture and CT direct fluorescent antibody
      vs. GC/CT nucleic acid amplification test) and clinical setting (primary care vs.
      HRA). Screening question operating characteristics were estimated using
      contingency table methods and then pooled across subcohorts. Among 803 patients,
      the prevalence of anorectal GC/CT varied from 3.5-20.1% in the 4 sub-cohorts. The
      sensitivity of the screening question for self-reported exposure to predict
      anorectal STI was higher in the primary care than in the HRA clinic, 86-100% vs.
      12-35%, respectively. The negative predictive value of the screening question to
      predict asymptomatic anorectal STI was > or = 90% in all sub-cohorts. In
      sensitivity analyses, the probability of being an unidentified case among those
      denying exposure increased from 0.4-8.1% in the primary care setting, and from
      0.9-18.8% in the HRA setting as the prevalence varied from 1-20%. CONCLUSION: As
      STI prevalence increases, denial of unprotected anal-receptive exposure leads to
      an increasingly unacceptable proportion of unidentified asymptomatic anorectal
      STI if used as a criterion not to obtain microbiologic assays.

PMID- 20041144
TI  - Cholesterol homeostasis in two commonly used human prostate cancer cell-lines,
      LNCaP and PC-3.
AB  - BACKGROUND: Recently, there has been renewed interest in the link between
      cholesterol and prostate cancer. It has been previously reported that in vitro,
      prostate cancer cells lack sterol-mediated feedback regulation of the major
      transcription factor in cholesterol homeostasis, sterol-regulatory element
      binding protein 2 (SREBP-2). This could explain the accumulation of cholesterol
      observed in clinical prostate cancers. Consequently, perturbed feedback
      regulation to increased sterol levels has become a pervasive concept in the
      prostate cancer setting. Here, we aimed to explore this in greater depth.
      METHODOLOGY/PRINCIPAL FINDINGS: After altering the cellular cholesterol status in
      LNCaP and PC-3 prostate cancer cells, we examined SREBP-2 processing, downstream
      effects on promoter activity and expression of SREBP-2 target genes, and
      functional activity (low-density lipoprotein uptake, cholesterol synthesis). In
      doing so, we observed that LNCaP and PC-3 cells were sensitive to increased
      sterol levels. In contrast, lowering cholesterol levels via statin treatment
      generated a greater response in LNCaP cells than PC-3 cells. This highlighted an
      important difference between these cell-lines: basal SREBP-2 activity appeared to
      be higher in PC-3 cells, reducing sensitivity to decreased cholesterol levels.
      CONCLUSION/SIGNIFICANCE: Thus, prostate cancer cells are sensitive to changing
      sterol levels in vitro, but the extent of this regulation differs between
      prostate cancer cell-lines. These results shed new light on the regulation of
      cholesterol metabolism in two commonly used prostate cancer cell-lines, and
      emphasize the importance of establishing whether or not cholesterol homeostasis
      is perturbed in prostate cancer in vivo.

PMID- 20041145
TI  - MiR-155 induction by F. novicida but not the virulent F. tularensis results in
      SHIP down-regulation and enhanced pro-inflammatory cytokine response.
AB  - The intracellular gram-negative bacterium Francisella tularensis causes the
      disease tularemia and is known for its ability to subvert host immune responses.
      Previous work from our laboratory identified the PI3K/Akt pathway and SHIP as
      critical modulators of host resistance to Francisella. Here, we show that SHIP
      expression is strongly down-regulated in monocytes and macrophages following
      infection with F. tularensis novicida (F.n.). To account for this negative
      regulation we explored the possibility that microRNAs (miRs) that target SHIP may
      be induced during infection. There is one miR that is predicted to target SHIP,
      miR-155. We tested for induction and found that F.n. induced miR-155 both in
      primary monocytes/macrophages and in vivo. Using luciferase reporter assays we
      confirmed that miR-155 led to down-regulation of SHIP, showing that it
      specifically targets the SHIP 3'UTR. Further experiments showed that miR-155 and
      BIC, the gene that encodes miR-155, were induced as early as four hours post
      infection in primary human monocytes. This expression was dependent on TLR2/MyD88
      and did not require inflammasome activation. Importantly, miR-155 positively
      regulated pro-inflammatory cytokine release in human monocytes infected with
      Francisella. In sharp contrast, we found that the highly virulent type A SCHU S4
      strain of Francisella tularensis (F.t.) led to a significantly lower miR-155
      response than the less virulent F.n. Hence, F.n. induces miR-155 expression and
      leads to down-regulation of SHIP, resulting in enhanced pro-inflammatory
      responses. However, impaired miR-155 induction by SCHU S4 may help explain the
      lack of both SHIP down-regulation and pro-inflammatory response and may account
      for the virulence of Type A Francisella.

PMID- 20041146
TI  - General epidemiological parameters of viral hepatitis A, B, C, and E in six
      regions of China: a cross-sectional study in 2007.
AB  - BACKGROUND: Viral hepatitis is a serious health burden worldwide. To date, few
      reports have addressed the prevalence of hepatitis A, B, C, and E in China.
      Therefore, the general epidemiological parameters of viral hepatitis remain
      unknown. PRINCIPAL FINDINGS: In this cross-sectional study, we performed a
      serological prevalence analysis of viral hepatitis A, B, C, and E in 8,762
      randomly selected Chinese subjects, which represented six areas of China. The
      overall prevalence of anti-Hepatitis C virus antibody (anti-HCV) was 0.58%, which
      was much lower than was estimated by WHO. The prevalences of Hepatitis B virus
      surface antigen (HBsAg), anti-Hepatitis B virus surface protein antibody (HBsAb),
      and anti-Hepatitis B virus core protein antibody (HBcAb) were 5.84%, 41.31%, and
      35.92%, respectively, whereas in the group of subjects less than 5 years old,
      these prevalences were 1.16%, 46.77%, and 8.69% respectively, which suggests that
      the Hepatitis B virus (HBV)-carrier population is decreasing, and the nationwide
      HBV vaccine program has contributed to the lowered HBV prevalence in the younger
      generation in China. Meanwhile, a large deficit remains in coverage provided by
      the national HBV immune program. In addition, our data suggested the possibility
      that HBsAb may not last long enough to protect people from HBV infection
      throughout life. The overall prevalence of anti-Hepatitis A virus antibody (anti
      HAV) and anti-Hepatitis E virus antibody (anti-HEV) were as high as 72.87% and
      17.66%, respectively. The indices increased with age, which suggests that a large
      proportion of Chinese adults are protected by latent infection. Furthermore, the
      pattern of HEV infection was significantly different among ethnic groups in
      China. CONCLUSIONS: Our study provided much important information concerning
      hepatitis A, B, C, and E prevalence in China and will contribute to worldwide
      oversight of viral hepatitis.

PMID- 20041147
TI  - The ZEB1 transcription factor is a novel repressor of adiposity in female mice.
AB  - BACKGROUND: Four genome-wide association studies mapped an "obesity" gene to
      human chromosome 10p11-12. As the zinc finger E-box binding homeobox 1 (ZEB1)
      transcription factor is encoded by the TCF8 gene located in that region, and as
      it influences the differentiation of various mesodermal lineages, we hypothesized
      that ZEB1 might also modulate adiposity. The goal of these studies was to test
      that hypothesis in mice. METHODOLOGY/PRINCIPAL FINDINGS: To ascertain whether fat
      accumulation affects ZEB1 expression, female C57BL/6 mice were fed a regular chow
      diet (RCD) ad libitum or a 25% calorie-restricted diet from 2.5 to 18.3 months of
      age. ZEB1 mRNA levels in parametrial fat were six to ten times higher in the
      obese mice. To determine directly whether ZEB1 affects adiposity, wild type (WT)
      mice and mice heterozygous for TCF8 (TCF8+/-) were fed an RCD or a high-fat diet
      (HFD) (60% calories from fat). By two months of age on an HFD and three months on
      an RCD, TCF8+/- mice were heavier than WT controls, which was attributed by Echo
      MRI to increased fat mass (at three months on an HFD: 0.517+/-0.081 total
      fat/lean mass versus 0.313+/-0.036; at three months on an RCD: 0.175+/-0.013
      versus 0.124+/-0.012). No differences were observed in food uptake or physical
      activity, suggesting that the genotypes differ in some aspect of their metabolic
      activity. ZEB1 expression also increases during adipogenesis in cell culture.
      CONCLUSION/SIGNIFICANCE: These results show for the first time that the ZEB1
      transcription factor regulates the accumulation of adipose tissue. Furthermore,
      they corroborate the genome-wide association studies that mapped an "obesity"
      gene at chromosome 10p11-12.

PMID- 20041148
TI  - Influence of two vaccination campaigns on genetic diversity of invasive Neisseria
      meningitidis isolates in northern Spain (1997-2008).
AB  - BACKGROUND: Neisseria meningitidis diversifies rapidly, due to its high
      recombination rates. The aim of this study was to analyze the possible impact of
      two vaccination campaigns (a once-off A/C polysaccharide vaccination campaign in
      people aged 18 months to 20 years old in 1997, and a meningococcal C conjugate
      vaccination campaign in children aged < or = 6 years old from 2000 to 2008) on
      diversification of the population of invasive isolates obtained between 1997 and
      2008. All of the 461 available isolates were included (2, 319, 123, 11 and 6
      belonging to serogroups A, B, C, Y and W-135, respectively).
      METHODOLOGY/PRINCIPAL FINDINGS: The isolates were analyzed for diversity using
      multilocus sequence typing, eBURST and the S.T.A.R.T.2 program. One hundred and
      seven sequence types (ST) and 20 clonal complexes were obtained. Five different
      STs (ST11, ST8, ST33, ST1163 and ST3496) included 56.4% of the isolates. With the
      exception of ST11, all other STs were associated with a specific serogroup.
      Epidemic circulation of serogroup C ST8 isolates was detected in 1997-1998, as
      well as epidemic circulation of ST11 isolates (serogroups B and C) in 2002-2004.
      The epidemic behavior of serogroup B ST11 (ST11_B:2a:P1.5) was similar, although
      with lesser intensity, to that of ST11 of serogroup C. Although clonality
      increased during epidemic years, the overall diversity of the meningococcal
      population did not increase throughout the 12 years of the study. CONCLUSION: The
      overall diversity of the meningococcal population, measured by the frequency of
      STs and clonal complexes, numbers of alleles, polymorphic sites, and index of
      association, remained relatively constant throughout the study period,
      contradicting previous findings by other researchers.

PMID- 20041149
TI  - The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in
      a murine model.
AB  - BACKGROUND: The interaction between Mycobacterium tuberculosis (Mtb) and host
      cells is complex and far from being understood. The role of the different
      receptor(s) implicated in the recognition of Mtb in particular remains poorly
      defined, and those that have been found to have activity in vitro were
      subsequently shown to be redundant in vivo. METHODS AND FINDINGS: To identify
      novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA
      library and identified scavenger receptor B class 1 (SR-B1) as a receptor for
      mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which
      mediates both the selective uptake of cholesteryl esters and the efflux of
      cholesterol, and has also recently been implicated in the recognition of other
      pathogens. We show here that mycobacteria can bind directly to SR-B1 on
      transfected cells, and that this interaction could be inhibited in the presence
      of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage
      populations, including alveolar macrophages, that express this receptor, however,
      no differences in the recognition and response to mycobacteria were observed in
      macrophages isolated from SR-B1(-/-) or wild type mice in vitro. Moreover, when
      wild type and SR-B1(-/-) animals were infected with a low dose of Mtb (100
      CFU/mouse) there were no alterations in survival, bacterial burdens, granuloma
      formation or cytokine production in the lung. However, significant reduction in
      the production of TNF, IFNgamma, and IL10 were observed in SR-B1(-/-) mice
      following infection with a high dose of Mtb (1000 CFU/mouse), which marginally
      affected the size of inflammatory foci but did not influence bacterial burdens.
      Deficiency of SR-B1 also had no effect on resistance to disease under conditions
      of varying dietary cholesterol. We did observe, however, that the presence of
      high levels of cholesterol in the diet significantly enhanced the bacterial
      burdens in the lung, but this was independent of SR-B1. CONCLUSION: SR-B1 is
      involved in mycobacterial recognition, but this receptor plays only a minor role
      in anti-mycobacterial immunity in vivo. Like many other receptors for these
      pathogens, the loss of SR-B1 can be functionally compensated for under normal
      conditions.

PMID- 20041150
TI  - Missense mutations in the MEFV gene are associated with fibromyalgia syndrome and
      correlate with elevated IL-1beta plasma levels.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS), a common, chronic, widespread
      musculoskeletal pain disorder found in 2% of the general population and with a
      preponderance of 85% in females, has both genetic and environmental
      contributions. Patients and their parents have high plasma levels of the
      chemokines MCP-1 and eotaxin, providing evidence for both a genetic and an
      immunological/inflammatory origin for the syndrome (Zhang et al., 2008, Exp.
      Biol. Med. 233: 1171-1180). METHODS AND FINDINGS: In a search for a candidate
      gene affecting inflammatory pathways, among five screened in our patient samples
      (100 probands with FMS and their parents), we found 10 rare and one common
      alleles for MEFV, a gene in which various compound heterozygous mutations lead to
      Familial Mediterranean Fever (FMF). A total of 2.63 megabases of genomic sequence
      of the MEFV gene were scanned by direct sequencing. The collection of rare
      missense mutations (all heterozygotes and tested in the aggregate) had a
      significant elevated frequency of transmission to affecteds (p = 0.0085, one
      sided, exact binomial test). Our data provide evidence that rare missense
      variants of the MEFV gene are, collectively, associated with risk of FMS and are
      present in a subset of 15% of FMS patients. This subset had, on average, high
      levels of plasma IL-1beta (p = 0.019) compared to FMS patients without rare
      variants, unaffected family members with or without rare variants, and unrelated
      controls of unknown genotype. IL-1beta is a cytokine associated with the function
      of the MEFV gene and thought to be responsible for its symptoms of fever and
      muscle aches. CONCLUSIONS: Since misregulation of IL-1beta expression has been
      predicted for patients with mutations in the MEFV gene, we conclude that patients
      heterozygous for rare missense variants of this gene may be predisposed to FMS,
      possibly triggered by environmental factors.

PMID- 20041151
TI  - Investigations of a rabbit (Oryctolagus cuniculus) model of systemic lupus
      erythematosus (SLE), BAFF and its receptors.
AB  - B-cell activation factor belonging to the tumor necrosis factor family (BAFF) is
      a major contributor to survival of B lymphocytes during development and
      maturation. A relationship between circulating BAFF levels and disease activity
      has been reported in patients with the autoimmune disease Systemic Lupus
      Erythematosus (SLE). Clinical trials targeting BAFF or its receptors are
      currently in progress. In order to further characterize a rabbit (Oryctolagus
      cuniculus) model of SLE, we investigated the expression of BAFF and its receptors
      in non-inbred, pedigreed rabbits derived from breeding and selection based on
      autoantibody responses. We immunized rabbits related to previous groups that
      developed autoantibodies and inflammatory responses after immunizations with
      peptides synthesized on multiple antigen-branched polylysine backbones. Blood and
      sera collected before immunization and after boosts were used for health
      monitoring, analyses of serum autoantibody responses by ELISA and
      immunofluorescence. Peripheral blood mononuclear cells (PBMC) were studied by
      flow cytometry and were the source of mRNA for quantitative PCR analyses. We
      hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly
      through BAFF receptor binding might increase in autoantibody-producing rabbits.
      Immunized rabbits developed elevated levels of leucocyte populations, anti
      nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC
      decreased and BAFF levels remained low and unchanged in most immunized rabbits.
      By flow cytometry, percentages of BAFF positive cells decreased. Percentages of
      transmembrane activator and CAML interactor (TACI) decreased in most rabbits from
      all the immunized groups. The rabbit is an important model for human autoimmune
      and infectious diseases, and a high quality draft rabbit genome assembly was
      recently completed. Human disease models developed in non-inbred pedigreed
      animals are better able to reflect the complexities of diseases such as SLE with
      familial patterns of inheritance. Although no consistent pattern of elevated
      expression of BAFF mRNA or protein was found in the rabbits studied, the data
      collected and reported here build upon previous data to refine understanding of a
      rabbit model of SLE.

PMID- 20041152
TI  - MEF2C silencing attenuates load-induced left ventricular hypertrophy by
      modulating mTOR/S6K pathway in mice.
AB  - BACKGROUND: The activation of the members of the myocyte enhancer factor-2 family
      (MEF2A, B, C and D) of transcription factors promotes cardiac hypertrophy and
      failure. However, the role of its individual components in the pathogenesis of
      cardiac hypertrophy remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study, we investigated whether MEF2C plays a role in mediating the left
      ventricular hypertrophy by pressure overload in mice. The knockdown of myocardial
      MEF2C induced by specific small interfering RNA (siRNA) has been shown to
      attenuate hypertrophy, interstitial fibrosis and the rise of ANP levels in aortic
      banded mice. We detected that the depletion of MEF2C also results in lowered
      levels of both PGC-1alpha and mitochondrial DNA in the overloaded left ventricle,
      associated with enhanced AMP:ATP ratio. Additionally, MEF2C depletion was
      accompanied by defective activation of S6K in response to pressure overload.
      Treatment with the amino acid leucine stimulated S6K and suppressed the
      attenuation of left ventricular hypertrophy and fibrosis in the aforementioned
      aortic banded mice. CONCLUSION/SIGNIFICANCE: These findings represent new
      evidences that MEF2C depletion attenuates the hypertrophic responses to
      mechanical stress and highlight the potential of MEF2C to be a target for new
      therapies to cardiac hypertrophy and failure.

PMID- 20041153
TI  - A gene expression signature of invasive potential in metastatic melanoma cells.
AB  - BACKGROUND: We are investigating the molecular basis of melanoma by defining
      genomic characteristics that correlate with tumour phenotype in a novel panel of
      metastatic melanoma cell lines. The aim of this study is to identify new
      prognostic markers and therapeutic targets that might aid clinical cancer
      diagnosis and management. PRINCIPAL FINDINGS: Global transcript profiling
      identified a signature featuring decreased expression of developmental and
      lineage specification genes including MITF, EDNRB, DCT, and TYR, and increased
      expression of genes involved in interaction with the extracellular environment,
      such as PLAUR, VCAN, and HIF1a. Migration assays showed that the gene signature
      correlated with the invasive potential of the cell lines, and external validation
      by using publicly available data indicated that tumours with the invasive gene
      signature were less melanocytic and may be more aggressive. The invasion
      signature could be detected in both primary and metastatic tumours suggesting
      that gene expression conferring increased invasive potential in melanoma may
      occur independently of tumour stage. CONCLUSIONS: Our data supports the
      hypothesis that differential developmental gene expression may drive invasive
      potential in metastatic melanoma, and that melanoma heterogeneity may be
      explained by the differing capacity of melanoma cells to both withstand decreased
      expression of lineage specification genes and to respond to the tumour
      microenvironment. The invasion signature may provide new possibilities for
      predicting which primary tumours are more likely to metastasize, and which
      metastatic tumours might show a more aggressive clinical course.

PMID- 20041154
TI  - Identification and developmental expression of Xenopus laevis SUMO proteases.
AB  - SUMO proteins are small ubiquitin-related modifiers. All SUMOs are synthesized as
      propeptides that are post-translationally cleaved prior to conjugation. After
      processing, SUMOs become covalently conjugated to cellular targets through a
      pathway that is similar to ubiquitination. Ubiquitin like protein
      proteases/Sentrin specific proteases (Ulp/SENPs) mediate both processing and
      deconjugation of SUMOs. The action of Ulp/SENPs makes SUMOylation a highly
      dynamic post-translational modification. To investigate how Ulp/SENPs are
      regulated in a developmental context, we isolated and characterized all Ulp/SENPs
      in Xenopus laevis. Xenopus possess homologues of mammalian SENP3, 5, 6 and 7. All
      of these enzymes reacted with HA-tagged vinyl sulfone derivatives of SUMO-2 (HA
      SU2-VS) but not SUMO-1 (HA-SU1-VS), suggesting that they act primarily on SUMO-2
      and -3. In contrast, Xenopus possess a single member of the SENP1/SENP2 subfamily
      of Ulp/SENPs, most closely related to mammalian SENP1. Xenopus SENP1 reacted with
      HA-SU1-VS and HA-SU2-VS, suggesting that it acts on all SUMO paralogues. We
      analyzed the mRNA and protein levels for each of the Ulp/SENPs through
      development; we found that they show distinct patterns of expression that may
      involve both transcriptional and post-transcriptional regulation. Finally, we
      have characterized the developmental function of the most abundant Ulp/SENP found
      within Xenopus eggs, SENP3. Depletion of SENP3 using morpholino antisense
      oligonucleotides (morpholinos) caused accumulation of high molecular weight SUMO
      2/3 conjugated species, defects in developing embryos and changes in the
      expression of some genes regulated by the transforming growth factor beta (TGF
      beta) pathway. These findings collectively indicate that SUMO proteases are both
      highly regulated and essential for normal development.

PMID- 20041155
TI  - Is our self nothing but reward? Neuronal overlap and distinction between reward
      and personal relevance and its relation to human personality.
AB  - BACKGROUND: The attribution of personal relevance, i.e. relating internal and
      external stimuli to establish a sense of belonging, is a common phenomenon in
      daily life. Although previous research demonstrated a relationship between reward
      and personal relevance, their exact neuronal relationship including the impact of
      personality traits remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using
      functional magnetic resonance imaging, we applied an experimental paradigm that
      allowed us to explore the neural response evoked by reward and the attribution of
      personal relevance separately. We observed different brain regions previously
      reported to be active during reward and personal relevance, including the
      bilateral caudate nucleus and the pregenual anterior cingulate cortex (PACC).
      Additional analysis revealed activations in the right and left insula specific
      for the attribution of personal relevance. Furthermore, our results demonstrate a
      negative correlation between signal changes in both the PACC and the left
      anterior insula during the attribution of low personal relevance and the
      personality dimension novelty seeking. CONCLUSION/SIGNIFICANCE: While a set of
      subcortical and cortical regions including the PACC is commonly involved in
      reward and personal relevance, other regions like the bilateral anterior insula
      were recruited specifically during personal relevance. Based on our correlation
      between novelty seeking and signal changes in both regions during personal
      relevance, we assume that the neuronal response to personally relevant stimuli is
      dependent on the personality trait novelty seeking.

PMID- 20041156
TI  - The WD40 domain is required for LRRK2 neurotoxicity.
AB  - BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common
      genetic cause of Parkinson disease (PD). LRRK2 contains an "enzymatic core"
      composed of GTPase and kinase domains that is flanked by leucine-rich repeat
      (LRR) and WD40 protein-protein interaction domains. While kinase activity and GTP
      binding have both been implicated in LRRK2 neurotoxicity, the potential role of
      other LRRK2 domains has not been as extensively explored. PRINCIPAL FINDINGS: We
      demonstrate that LRRK2 normally exists in a dimeric complex, and that removing
      the WD40 domain prevents complex formation and autophosphorylation. Moreover,
      loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD
      mutations. CONCLUSION: These findings suggest that LRRK2 dimerization and
      autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations
      and highlight a potential role for the WD40 domain in the mechanism of LRRK2
      mediated cell death.

PMID- 20041157
TI  - Activation of Wnt/beta-catenin signaling increases insulin sensitivity through a
      reciprocal regulation of Wnt10b and SREBP-1c in skeletal muscle cells.
AB  - BACKGROUND: Intramyocellular lipid accumulation is strongly related to insulin
      resistance in humans, and we have shown that high glucose concentration induced
      de novo lipogenesis and insulin resistance in murin muscle cells. Alterations in
      Wnt signaling impact the balance between myogenic and adipogenic programs in
      myoblasts, partly due to the decrease of Wnt10b protein. As recent studies point
      towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, we
      hypothesized that activation of Wnt signaling could play a crucial role in muscle
      insulin sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that
      SREBP-1c and Wnt10b display inverse expression patterns during muscle ontogenesis
      and regeneration, as well as during satellite cells differentiation. The Wnt/beta
      catenin pathway was reactivated in contracting myotubes using siRNA mediated
      SREBP-1 knockdown, Wnt10b over-expression or inhibition of GSK-3beta, whereas Wnt
      signaling was inhibited in myoblasts through silencing of Wnt10b. SREBP-1
      knockdown was sufficient to induce Wnt10b protein expression in contracting
      myotubes and to activate the Wnt/beta-catenin pathway. Conversely, silencing
      Wnt10b in myoblasts induced SREBP-1c protein expression, suggesting a reciprocal
      regulation. Stimulation of the Wnt/beta-catenin pathway i) drastically decreased
      SREBP-1c protein and intramyocellular lipid deposition in myotubes; ii) increased
      basal glucose transport in both insulin-sensitive and insulin-resistant myotubes
      through a differential activation of Akt and AMPK pathways; iii) restored insulin
      sensitivity in insulin-resistant myotubes. CONCLUSIONS/SIGNIFICANCE: We conclude
      that activation of Wnt/beta-catenin signaling in skeletal muscle cells improved
      insulin sensitivity by i) decreasing intramyocellular lipid deposition through
      downregulation of SREBP-1c; ii) increasing insulin effects through a differential
      activation of the Akt/PKB and AMPK pathways; iii) inhibiting the MAPK pathway. A
      crosstalk between these pathways and Wnt/beta-catenin signaling in skeletal
      muscle opens the exciting possibility that organ-selective modulation of Wnt
      signaling might become an attractive therapeutic target in regenerative medicine
      and to treat obese and diabetic populations.

PMID- 20041158
TI  - Genetics, recombination and clinical features of human rhinovirus species C (HRV
      C) infections; interactions of HRV-C with other respiratory viruses.
AB  - To estimate the frequency, molecular epidemiological and clinical associations of
      infection with the newly described species C variants of human rhinoviruses
      (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in
      Edinburgh were screened using a VP4-encoding region-based selective polymerase
      chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other
      respiratory viruses. HRV-C was the third most frequently detected behind
      respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes
      detected among 1885 subjects over 13 months (7.5%). Infections predominantly
      targeted the very young (median age 6-12 months; 80% of infections in those <2
      years), occurred throughout the year but with peak incidence in early winter
      months. HRV-C was detected significantly more frequently among subjects with
      lower (LRT) and upper respiratory tract (URT) disease than controls without
      respiratory symptoms; HRV-C mono-infections were the second most frequently
      detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all
      cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39
      genotypically defined types, increasing the current total worldwide to 60.
      Through sequence comparisons of the 5'untranslated region (5'UTR), the majority
      grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming
      a phylogenetically distinct 5'UTR group (HRV-Cc). Multiple and bidirectional
      recombination events between HRV-Ca and HRV-Cc variants and with HRV species A
      represents the most parsimonious explanation for their interspersed phylogeny
      relationships in the VP4/VP2-encoding region. No difference in age distribution,
      seasonality or disease associations was identified between HRV-Ca and HRV-Cc
      variants. HRV-C-infected subjects showed markedly reduced detection frequencies
      of RSV and other respiratory viruses, providing evidence for a major interfering
      effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's
      disease associations, its prevalence and evidence for interfering effects on
      other respiratory viruses mandates incorporation of rhinoviruses into future
      diagnostic virology screening.

PMID- 20041159
TI  - Reverse evolution: driving forces behind the loss of acquired photosynthetic
      traits.
AB  - BACKGROUND: The loss of photosynthesis has occurred often in eukaryotic
      evolution, even more than its acquisition, which occurred at least nine times
      independently and which generated the evolution of the supergroups
      Archaeplastida, Rhizaria, Chromalveolata and Excavata. This secondary loss of
      autotrophic capability is essential to explain the evolution of eukaryotes and
      the high diversity of protists, which has been severely underestimated until
      recently. However, the ecological and evolutionary scenarios behind this
      evolutionary "step back" are still largely unknown. METHODOLOGY/PRINCIPAL
      FINDINGS: Using a dynamic model of heterotrophic and mixotrophic flagellates and
      two types of prey, large bacteria and ultramicrobacteria, we examine the
      influence of DOC concentration, mixotroph's photosynthetic growth rate, and
      external limitations of photosynthesis on the coexistence of both types of
      flagellates. Our key premises are: large bacteria grow faster than small ones at
      high DOC concentrations, and vice versa; and heterotrophic flagellates are more
      efficient than the mixotrophs grazing small bacteria (both empirically
      supported). We show that differential efficiency in bacteria grazing, which
      strongly depends on cell size, is a key factor to explain the loss of
      photosynthesis in mixotrophs (which combine photosynthesis and bacterivory)
      leading to purely heterotrophic lineages. Further, we show in what conditions an
      heterotroph mutant can coexist, or even out-compete, its mixotrophic ancestor,
      suggesting that bacterivory and cell size reduction may have been major triggers
      for the diversification of eukaryotes. CONCLUSIONS/SIGNIFICANCE: Our results
      suggest that, provided the mixotroph's photosynthetic advantage is not too large,
      the (small) heterotroph will also dominate in nutrient-poor environments and will
      readily invade a community of mixotrophs and bacteria, due to its higher
      efficiency exploiting the ultramicrobacteria. As carbon-limited conditions were
      presumably widespread throughout Earth history, such a scenario may explain the
      numerous transitions from phototrophy to mixotrophy and further to heterotrophy
      within virtually all major algal lineages. We challenge prevailing concepts that
      affiliated the evolution of phagotrophy with eutrophic or strongly light-limited
      environments only.

PMID- 20041160
TI  - MiR-24 tumor suppressor activity is regulated independent of p53 and through a
      target site polymorphism.
AB  - MicroRNAs (miRNAs) are predicted to regulate approximately 30% of all human
      genes; however, only a few miRNAs have been assigned their targets and specific
      functions. Here we demonstrate that miR-24, a ubiquitously expressed miRNA, has
      an anti-proliferative effect independent of p53 function. Cell lines with
      differential p53 status were used as a model to study the effects of miR-24 on
      cell proliferation, cell cycle control, gene regulation and cellular
      transformation. Overexpression of miR-24 in six different cell lines, independent
      of p53 function, inhibited cell proliferation and resulted in G2/S cell cycle
      arrest. MiR-24 over expression in cells with wt-p53 upregulated TP53 and p21
      protein; however, in p53-null cells miR-24 still induced cell cycle arrest
      without the involvement of p21. We show that miR-24 regulates p53-independent
      cellular proliferation by regulating an S-phase enzyme, dihydrofolate reductase
      (DHFR) a target of the chemotherapeutic drug methotrexate (MTX). Of interest, we
      found that a miR-24 target site polymorphism in DHFR 3' UTR that results in loss
      of miR-24-function and high DHFR levels in the cell imparts a growth advantage to
      immortalized cells and induces neoplastic transformation. Of clinical
      significance, we found that miR-24 is deregulated in human colorectal cancer
      tumors and a subset of tumors has reduced levels of miR-24. A novel function for
      miR-24 as a p53-independent cell cycle inhibitory miRNA is proposed.

PMID- 20041161
TI  - Proteomic detection of non-annotated protein-coding genes in Pseudomonas
      fluorescens Pf0-1.
AB  - Genome sequences are annotated by computational prediction of coding sequences,
      followed by similarity searches such as BLAST, which provide a layer of possible
      functional information. While the existence of processes such as alternative
      splicing complicates matters for eukaryote genomes, the view of bacterial genomes
      as a linear series of closely spaced genes leads to the assumption that
      computational annotations that predict such arrangements completely describe the
      coding capacity of bacterial genomes. We undertook a proteomic study to identify
      proteins expressed by Pseudomonas fluorescens Pf0-1 from genes that were not
      predicted during the genome annotation. Mapping peptides to the Pf0-1 genome
      sequence identified sixteen non-annotated protein-coding regions, of which nine
      were antisense to predicted genes, six were intergenic, and one read in the same
      direction as an annotated gene but in a different frame. The expression of all
      but one of the newly discovered genes was verified by RT-PCR. Few clues as to the
      function of the new genes were gleaned from informatic analyses, but potential
      orthologs in other Pseudomonas genomes were identified for eight of the new
      genes. The 16 newly identified genes improve the quality of the Pf0-1 genome
      annotation, and the detection of antisense protein-coding genes indicates the
      under-appreciated complexity of bacterial genome organization.

PMID- 20041162
TI  - Real-time imaging and quantification of amyloid-beta peptide aggregates by novel
      quantum-dot nanoprobes.
AB  - BACKGROUND: Protein aggregation plays a major role in the pathogenesis of
      neurodegenerative disorders, such as Alzheimer's disease. However, direct real
      time imaging of protein aggregation, including oligomerization and
      fibrillization, has never been achieved. Here we demonstrate the preparation of
      fluorescent semiconductor nanocrystal (quantum dot; QD)-labeled amyloid-beta
      peptide (QDAbeta) and its advanced applications. METHODOLOGY/PRINCIPAL FINDINGS:
      The QDAbeta construct retained Abeta oligomer-forming ability, and the sizes of
      these oligomers could be estimated from the relative fluorescence intensities of
      the imaged spots. Both QDAbeta coaggregation with intact Abeta42 and insertion
      into fibrils were detected by fluorescence microscopy. The coaggregation process
      was observed by real-time 3D imaging using slit-scanning confocal microscopy,
      which showed a typical sigmoid curve with 1.5 h in the lag-time and 12 h until
      saturation. Inhibition of coaggregation using an anti-Abeta antibody can be
      observed as 3D images on a microscopic scale. Microglia ingested monomeric
      QDAbeta more significantly than oligomeric QDAbeta, and the ingested QDAbeta was
      mainly accumulated in the lysosome. CONCLUSIONS/SIGNIFICANCE: These data
      demonstrate that QDAbeta is a novel nanoprobe for studying Abeta oligomerization
      and fibrillization in multiple modalities and may be applicable for high
      throughput drug screening systems.

PMID- 20041163
TI  - Critical early roles for col27a1a and col27a1b in zebrafish notochord
      morphogenesis, vertebral mineralization and post-embryonic axial growth.
AB  - BACKGROUND: Fibrillar collagens are well known for their links to human diseases,
      with which all have been associated except for the two most recently identified
      fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess
      functions and potential disease phenotypes of type XXVII collagen, we examined
      its roles in zebrafish embryonic and post-embryonic development.
      METHODOLOGY/PRINCIPAL FINDINGS: We identified two type XXVII collagen genes in
      zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in
      notochord and cartilage in the embryo and early larva. To determine sites of type
      XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino
      antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with
      col27a1b resulted in curvature of the notochord at early stages and formation of
      scoliotic curves as well as dysmorphic vertebrae at later stages. These defects
      were accompanied by abnormal distributions of cells and protein localization in
      the notochord, as visualized by transmission electron microscopy, as well as
      delayed vertebral mineralization as detected histologically.
      CONCLUSIONS/SIGNIFICANCE: Together, our findings indicate a key role for type
      XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a
      possible human disease phenotype.

PMID- 20041164
TI  - Extraordinary molecular evolution in the PRDM9 fertility gene.
AB  - Recent work indicates that allelic incompatibility in the mouse PRDM9 (Meisetz)
      gene can cause hybrid male sterility, contributing to genetic isolation and
      potentially speciation. The only phenotype of mouse PRDM9 knockouts is a meiosis
      I block that causes sterility in both sexes. The PRDM9 gene encodes a protein
      with histone H3(K4) trimethyltransferase activity, a KRAB domain, and a DNA
      binding domain consisting of multiple tandem C2H2 zinc finger (ZF) domains. We
      have analyzed human coding polymorphism and interspecies evolutionary changes in
      the PRDM9 gene. The ZF domains of PRDM9 are evolving very rapidly, with
      compelling evidence of positive selection in primates. Positively selected amino
      acids are predominantly those known to make nucleotide specific contacts in C2H2
      zinc fingers. These results suggest that PRDM9 is subject to recurrent selection
      to change DNA-binding specificity. The human PRDM9 protein is highly polymorphic
      in its ZF domains and nearly all polymorphisms affect the same nucleotide contact
      residues that are subject to positive selection. ZF domain nucleotide sequences
      are strongly homogenized within species, indicating that interfinger
      recombination contributes to their evolution. PRDM9 has previously been assumed
      to be a transcription factor required to induce meiosis specific genes, a role
      that is inconsistent with its molecular evolution. We suggest instead that PRDM9
      is involved in some aspect of centromere segregation conflict and that rapidly
      evolving centromeric DNA drives changes in PRDM9 DNA-binding domains.

PMID- 20041165
TI  - F11-mediated inhibition of RhoA signalling enhances the spread of vaccinia virus
      in vitro and in vivo in an intranasal mouse model of infection.
AB  - The cortical actin cytoskeleton beneath the plasma membrane represents a physical
      barrier that vaccinia virus has to overcome during its exit from an infected
      cell. Previous observations using overexpression and pharmacological approaches
      suggest that vaccinia enhances its release by modulating the cortical actin
      cytoskeleton by inhibiting RhoA signalling using the viral protein F11. We have
      now examined the role of F11 and its ability to interact with RhoA to inhibit its
      downstream signalling in the spread of vaccinia infection both in vitro and in
      vivo. Live cell imaging over 48 hours reveals that loss of F11 or its ability to
      bind RhoA dramatically reduces the rate of cell-to-cell spread of the virus in a
      cell monolayer. Cells infected with the DeltaF11L virus also maintained their
      cell-to-cell contacts, and did not undergo virus-induced motility as observed
      during wild-type infections. The DeltaF11L virus is also attenuated in intranasal
      mouse models of infection, as it is impaired in its ability to spread from the
      initial sites of infection to the lungs and spleen. Loss of the ability of F11 to
      bind RhoA also reduces viral spread in vivo. Our results clearly establish that
      viral-mediated inhibition of RhoA signalling can enhance the spread of infection
      not only in cell monolayers, but also in vivo.

PMID- 20041166
TI  - Common genetic variation and the control of HIV-1 in humans.
AB  - To extend the understanding of host genetic determinants of HIV-1 control, we
      performed a genome-wide association study in a cohort of 2,554 infected Caucasian
      subjects. The study was powered to detect common genetic variants explaining down
      to 1.3% of the variability in viral load at set point. We provide overwhelming
      confirmation of three associations previously reported in a genome-wide study and
      show further independent effects of both common and rare variants in the Major
      Histocompatibility Complex region (MHC). We also examined the polymorphisms
      reported in previous candidate gene studies and fail to support a role for any
      variant outside of the MHC or the chemokine receptor cluster on chromosome 3. In
      addition, we evaluated functional variants, copy-number polymorphisms, epistatic
      interactions, and biological pathways. This study thus represents a comprehensive
      assessment of common human genetic variation in HIV-1 control in Caucasians.

PMID- 20041167
TI  - Perceptions of tuberculosis patients on provider-initiated HIV testing and
      counseling--a study from south India.
AB  - BACKGROUND: The acceptability and feasibility of provider-initiated HIV testing
      and counseling (PITC) in many settings across Asia with concentrated HIV
      epidemics is not known. A pilot study of the PITC policy undertaken within the
      public health care systems in two districts in India offered the opportunity to
      understand patient's perspectives on the process of referral for HIV testing and
      linking to HIV treatment and care. METHODS: We conducted a cross-sectional study
      of randomly selected TB patients registered by the TB control program between
      July and November 2007 in two districts in south India. Trained interviewers met
      patients shortly after TB diagnosis and administered a structured questionnaire.
      Patients were assessed regarding their experience with HIV status assessment,
      referral for counseling and testing, and for HIV-infected patients the counseling
      itself and subsequent referral for HIV treatment and care. RESULTS: Of the 568
      interviewed TB patients, 455 (80%) reported being referred for HIV testing after
      they presented to the health facility for investigations or treatment for TB.
      Over half the respondents reported having to travel long distances and incurred
      financial difficulties in reaching the Integrated Counselling and Testing Centre
      (ICTC) and two-thirds had to make more than two visits. Only 48% reported having
      been counseled before the test. Of the 110 HIV-infected patients interviewed,
      (including 43 with previously-known positive HIV status and 67 detected by PITC),
      89 (81%) reported being referred for anti-retroviral treatment (ART); 82 patients
      reached the ART centre but only 44 had been initiated on ART. CONCLUSIONS: This
      study provides the first evidence from India that routine, provider-initiated
      voluntary HIV testing of TB patients is acceptable, feasible and can be achieved
      with very high efficiency under programmatic conditions. While PITC is useful in
      identifying new HIV-infected patients so that they can be successfully linked to
      ART, the convenience and proximity of testing centres, quality of HIV counseling,
      and efficiency of ART services need attention.

PMID- 20041168
TI  - The inflammasomes.

PMID- 20041169
TI  - Three dimensional structure of the MqsR:MqsA complex: a novel TA pair comprised
      of a toxin homologous to RelE and an antitoxin with unique properties.
AB  - One mechanism by which bacteria survive environmental stress is through the
      formation of bacterial persisters, a sub-population of genetically identical
      quiescent cells that exhibit multidrug tolerance and are highly enriched in
      bacterial toxins. Recently, the Escherichia coli gene mqsR (b3022) was identified
      as the gene most highly upregulated in persisters. Here, we report multiple
      individual and complex three-dimensional structures of MqsR and its antitoxin
      MqsA (B3021), which reveal that MqsR:MqsA form a novel toxin:antitoxin (TA) pair.
      MqsR adopts an alpha/beta fold that is homologous with the RelE/YoeB family of
      bacterial ribonuclease toxins. MqsA is an elongated dimer that neutralizes MqsR
      toxicity. As expected for a TA pair, MqsA binds its own promoter. Unexpectedly,
      it also binds the promoters of genes important for E. coli physiology (e.g.,
      mcbR, spy). Unlike canonical antitoxins, MqsA is also structured throughout its
      entire sequence, binds zinc and coordinates DNA via its C- and not N-terminal
      domain. These studies reveal that TA systems, especially the antitoxins, are
      significantly more diverse than previously recognized and provide new insights
      into the role of toxins in maintaining the persister state.

PMID- 20041170
TI  - A novel phase variation mechanism in the meningococcus driven by a ligand
      responsive repressor and differential spacing of distal promoter elements.
AB  - Phase variable expression, mediated by high frequency reversible changes in the
      length of simple sequence repeats, facilitates adaptation of bacterial
      populations to changing environments and is frequently important in bacterial
      virulence. Here we elucidate a novel phase variable mechanism for NadA, an
      adhesin and invasin of Neisseria meningitidis. The NadR repressor protein binds
      to operators flanking the phase variable tract and contributes to the
      differential expression levels of phase variant promoters with different numbers
      of repeats likely due to different spacing between operators. We show that IHF
      binds between these operators, and may permit looping of the promoter, allowing
      interaction of NadR at operators located distally or overlapping the promoter.
      The 4-hydroxyphenylacetic acid, a metabolite of aromatic amino acid catabolism
      that is secreted in saliva, induces NadA expression by inhibiting the DNA binding
      activity of the repressor. When induced, only minor differences are evident
      between NadR-independent transcription levels of promoter phase variants and are
      likely due to differential RNA polymerase contacts leading to altered promoter
      activity. Our results suggest that NadA expression is under both stochastic and
      tight environmental-sensing regulatory control, both mediated by the NadR
      repressor, and may be induced during colonization of the oropharynx where it
      plays a major role in the successful adhesion and invasion of the mucosa. Hence,
      simple sequence repeats in promoter regions may be a strategy used by host
      adapted bacterial pathogens to randomly switch between expression states that may
      nonetheless still be induced by appropriate niche-specific signals.

PMID- 20041171
TI  - Order and stochastic dynamics in Drosophila planar cell polarity.
AB  - Cells in the wing blade of Drosophila melanogaster exhibit an in-plane
      polarization causing distal orientation of hairs. Establishment of the Planar
      Cell Polarity (PCP) involves intercellular interactions as well as a global
      orienting signal. Many of the genetic and molecular components underlying this
      process have been experimentally identified and a recently advanced system-level
      model has suggested that the observed mutant phenotypes can be understood in
      terms of intercellular interactions involving asymmetric localization of membrane
      bound proteins. Among key open questions in understanding the emergence of
      ordered polarization is the effect of stochasticity and the role of the global
      orienting signal. These issues relate closely to our understanding of
      ferromagnetism in physical systems. Here we pursue this analogy to understand the
      emergence of PCP order. To this end we develop a semi-phenomenological
      representation of the underlying molecular processes and define a "phase diagram"
      of the model which provides a global view of the dependence of the phenotype on
      parameters. We show that the dynamics of PCP has two regimes: rapid growth in the
      amplitude of local polarization followed by a slower process of alignment which
      progresses from small to large scales. We discuss the response of the tissue to
      various types of orienting signals and show that global PCP order can be achieved
      with a weak orienting signal provided that it acts during the early phase of the
      process. Finally we define and discuss some of the experimental predictions of
      the model.

PMID- 20041172
TI  - Introduction to the quantitative analysis of two-dimensional fluorescence
      microscopy images for cell-based screening.

PMID- 20041173
TI  - A unique role for the host ESCRT proteins in replication of Tomato bushy stunt
      virus.
AB  - Plus-stranded RNA viruses replicate in infected cells by assembling viral
      replicase complexes consisting of viral- and host-coded proteins. Previous genome
      wide screens with Tomato bushy stunt tombusvirus (TBSV) in a yeast model host
      revealed the involvement of seven ESCRT (endosomal sorting complexes required for
      transport) proteins in viral replication. In this paper, we show that the
      expression of dominant negative Vps23p, Vps24p, Snf7p, and Vps4p ESCRT factors
      inhibited virus replication in the plant host, suggesting that tombusviruses co
      opt selected ESCRT proteins for the assembly of the viral replicase complex. We
      also show that TBSV p33 replication protein interacts with Vps23p ESCRT-I and
      Bro1p accessory ESCRT factors. The interaction with p33 leads to the recruitment
      of Vps23p to the peroxisomes, the sites of TBSV replication. The viral replicase
      showed reduced activity and the minus-stranded viral RNA in the replicase became
      more accessible to ribonuclease when derived from vps23Delta or vps24Delta yeast,
      suggesting that the protection of the viral RNA is compromised within the
      replicase complex assembled in the absence of ESCRT proteins. The recruitment of
      ESCRT proteins is needed for the precise assembly of the replicase complex, which
      might help the virus evade recognition by the host defense surveillance system
      and/or prevent viral RNA destruction by the gene silencing machinery.

PMID- 20041175
TI  - Emergent patterns of social affiliation in primates, a model.
AB  - Many patterns of affiliative behaviour have been described for primates, for
      instance: reciprocation and exchange of grooming, grooming others of similar
      rank, reconciliation of fights, and preferential reconciliation with more
      valuable partners. For these patterns several functions and underlying cognitive
      processes have been suggested. It is, however, difficult to imagine how animals
      may combine these diverse considerations in their mind. Although the co-variation
      hypothesis, by limiting the social possibilities an individual has, constrains
      the number of cognitive considerations an individual has to take, it does not
      present an integrated theory of affiliative patterns either. In the present
      paper, after surveying patterns of affiliation in egalitarian and despotic
      macaques, we use an individual-based model with a high potential for self
      organisation as a starting point for such an integrative approach. In our model,
      called GrooFiWorld, individuals group and, upon meeting each other, may perform a
      dominance interaction of which the outcomes of winning and losing are self
      reinforcing. Besides, if individuals think they will be defeated, they consider
      grooming others. Here, the greater their anxiety is, the greater their
      "motivation" to groom others. Our model generates patterns similar to many
      affiliative patterns of empirical data. By merely increasing the intensity of
      aggression, affiliative patterns in the model change from those resembling
      egalitarian macaques to those resembling despotic ones. Our model produces such
      patterns without assuming in the mind of the individual the specific cognitive
      processes that are usually thought to underlie these patterns (such as
      recordkeeping of the acts given and received, a tendency to exchange, memory of
      the former fight, selective attraction to the former opponent, and estimation of
      the value of a relationship). Our model can be used as a null model to increase
      our understanding of affiliative behaviour among primates, in particular
      macaques.

PMID- 20041174
TI  - Th1-Th17 cells mediate protective adaptive immunity against Staphylococcus aureus
      and Candida albicans infection in mice.
AB  - We sought to define protective mechanisms of immunity to Staphylococcus aureus
      and Candida albicans bloodstream infections in mice immunized with the
      recombinant N-terminus of Als3p (rAls3p-N) vaccine plus aluminum hydroxide
      (Al(OH(3)) adjuvant, or adjuvant controls. Deficiency of IFN-gamma but not IL-17A
      enhanced susceptibility of control mice to both infections. However, vaccine
      induced protective immunity against both infections required CD4+ T-cell-derived
      IFN-gamma and IL-17A, and functional phagocytic effectors. Vaccination primed
      Th1, Th17, and Th1/17 lymphocytes, which produced pro-inflammatory cytokines that
      enhanced phagocytic killing of both organisms. Vaccinated, infected mice had
      increased IFN-gamma, IL-17, and KC, increased neutrophil influx, and decreased
      organism burden in tissues. In summary, rAls3p-N vaccination induced a Th1/Th17
      response, resulting in recruitment and activation of phagocytes at sites of
      infection, and more effective clearance of S. aureus and C. albicans from
      tissues. Thus, vaccine-mediated adaptive immunity can protect against both
      infections by targeting microbes for destruction by innate effectors.

PMID- 20041176
TI  - Inducible nucleosome depletion at OREBP-binding-sites by hypertonic stress.
AB  - BACKGROUND: Osmotic Response Element-Binding Protein (OREBP), also known as
      TonEBP or NFAT5, is a unique transcription factor. It is hitherto the only known
      mammalian transcription factor that regulates hypertonic stress-induced gene
      transcription. In addition, unlike other monomeric members of the NFAT family,
      OREBP exists as a homodimer and it is the only transcription factor known to bind
      naked DNA targets by complete encirclement in vitro. Nevertheless, how OREBP
      interacts with target DNA, also known as ORE/TonE, and how it elicits gene
      transcription in vivo, remains unknown. METHODOLOGY: Using hypertonic induction
      of the aldose reductase (AR) gene activation as a model, we showed that OREs
      contained dynamic nucleosomes. Hypertonic stress induced a rapid and reversible
      loss of nucleosome(s) around the OREs. The loss of nucleosome(s) was found to be
      initiated by an OREBP-independent mechanism, but was significantly potentiated in
      the presence of OREBP. Furthermore, hypertonic induction of AR gene was
      associated with an OREBP-dependent hyperacetylation of histones that spanned the
      5' upstream sequences and at least some exons of the gene. Nevertheless,
      nucleosome loss was not regulated by the acetylation status of histone.
      SIGNIFICANCE: Our findings offer novel insights into the mechanism of OREBP
      dependent transcriptional regulation and provide a basis for understanding how
      histone eviction and transcription factor recruitment are coupled.

PMID- 20041177
TI  - Increased light exposure alleviates one form of photoreceptor degeneration marked
      by elevated calcium in the dark.
AB  - BACKGROUND: In one group of gene mutations that cause photoreceptor degeneration
      in human patients, guanylyl cyclase is overactive in the dark. The ensuing excess
      opening of cGMP-gated cation channels causes intracellular calcium to rise to
      toxic levels. The Y99C mutation in guanylate cyclase-activating protein 1 (GCAP1)
      has been shown to act this way. We determined whether prolonged light exposure,
      which lowers cGMP levels through activation of phototransduction, might protect
      photoreceptors in a line of transgenic mice carrying the GCAP1-Y99C.
      METHODOLOGY/PRINCIPAL FINDINGS: We reared cohorts of GCAP1-Y99C transgenic mice
      under standard cyclic, constant dark and constant light conditions. Mouse eyes
      were analyzed by histology and by immunofluorescence for GFAP upregulation, a non
      specific marker for photoreceptor degeneration. Full-field electroretinograms
      (ERGs) were recorded to assess retinal function. Consistent with our hypothesis,
      constant darkness accelerated disease, while continuous lighting arrested
      photoreceptor degeneration. CONCLUSIONS/SIGNIFICANCE: In contrast to most forms
      of retinal degeneration, which are exacerbated by increased exposure to ambient
      light, a subset with mutations that cause overly active guanylyl cyclase and high
      intracellular calcium benefitted from prolonged light exposure. These findings
      may have therapeutic implications for patients with these types of genetic
      defects.

PMID- 20041178
TI  - Universal behavior of extreme price movements in stock markets.
AB  - Many studies assume stock prices follow a random process known as geometric
      Brownian motion. Although approximately correct, this model fails to explain the
      frequent occurrence of extreme price movements, such as stock market crashes.
      Using a large collection of data from three different stock markets, we present
      evidence that a modification to the random model--adding a slow, but significant,
      fluctuation to the standard deviation of the process--accurately explains the
      probability of different-sized price changes, including the relative high
      frequency of extreme movements. Furthermore, we show that this process is similar
      across stocks so that their price fluctuations can be characterized by a single
      curve. Because the behavior of price fluctuations is rooted in the
      characteristics of volatility, we expect our results to bring increased interest
      to stochastic volatility models, and especially to those that can produce the
      properties of volatility reported here.

PMID- 20041179
TI  - Cultivated grapevines represent a symptomless reservoir for the transmission of
      hop stunt viroid to hop crops: 15 years of evolutionary analysis.
AB  - Hop stunt was a mysterious disorder that first emerged in the 1940s in commercial
      hops in Japan. To investigate the origin of this disorder, we infected hops with
      natural Hop stunt viroid (HpSVd) isolates derived from four host species (hop,
      grapevine, plum and citrus), which except for hop represent possible sources of
      the ancestral viroid. These plants were maintained for 15 years, then analyzed
      the HpSVd variants present. Here we show that the variant originally found in
      cultivated grapevines gave rise to various combinations of mutations at positions
      25, 26, 54, 193, and 281. However, upon prolonged infection, these variants
      underwent convergent evolution resulting in a limited number of adapted mutants.
      Some of them showed nucleotide sequences identical to those currently responsible
      for hop stunt epidemics in commercial hops in Japan, China, and the United
      States. Therefore, these results indicate that we have successfully reproduced
      the original process by which a natural HpSVd variant naturally introduced into
      cultivated hops was able to mutate into the HpSVd variants that are currently
      present in commercial hops. Furthermore, and importantly, we have identified
      cultivated grapevines as a symptomless reservoir in which HSVd can evolve and be
      transmitted to hop crops to cause epidemics.

PMID- 20041180
TI  - Dissecting the signaling events that impact classical nuclear import and target
      nuclear transport factors.
AB  - BACKGROUND: Signaling through MEK-->ERK1/2 and PI3 kinases is implicated in many
      aspects of cell physiology, including the survival of oxidant exposure. Oxidants
      play a role in numerous physiological and pathophysiological processes, many of
      which rely on transport in and out of the nucleus. However, how oxidative stress
      impacts nuclear trafficking is not well defined. METHODOLOGY/PRINCIPAL FINDINGS:
      To better understand the effect of stress on nucleocytoplasmic trafficking, we
      exposed cells to the oxidant diethyl maleate. This treatment activated MEK-
      >ERK1/2 as well as PI3 kinase-->Akt cascades and triggered the inhibition of
      classical nuclear import. To define the molecular mechanisms that regulate
      nuclear transport, we examined whether MEK and PI3 kinase signaling affected the
      localization of key transport factors. Using recently developed tools for image
      acquisition and analysis, the subcellular distributions of importin-alpha, CAS,
      and nucleoporins Nup153 and Nup88 were quantified in different cellular
      compartments. These studies identified specific profiles for the localization of
      transport factors in the nucleus and cytoplasm, and at the nuclear envelope. Our
      results demonstrate that MEK and PI3 kinase signaling as well as oxidative stress
      control nuclear trafficking and the localization of transport components.
      Furthermore, stress not only induced changes in transport factor distribution,
      but also upregulated post-translational modification of transport factors. Our
      results are consistent with the idea that the phosphorylation of importin-alpha,
      CAS, Nup153, and Nup88, and the O-GlcNAc modification of Nup153 increase when
      cells are exposed to oxidant. CONCLUSIONS/SIGNIFICANCE: Our studies defined the
      complex regulation of classical nuclear import and identified key transport
      factors that are targeted by stress, MEK, and PI3 kinase signaling.

PMID- 20041181
TI  - Hemozoin (malarial pigment) directly promotes apoptosis of erythroid precursors.
AB  - Severe malarial anemia is the most common syndrome of severe malaria in endemic
      areas. The pathophysiology of chronic malaria is characterised by a striking
      degree of abnormal development of erythroid precursors (dyserythropoiesis) and an
      inadequate erythropoietic response in spite of elevated levels of erythropoietin.
      The cause of dyserythropoiesis is unclear although it has been suggested that
      bone-marrow macrophages release cytokines, chemokines or lipo-peroxides after
      exposure to hemozoin, a crystalloid form of undigested heme moieties from
      malarial infected erythrocytes, and so inhibit erythropoiesis. However, we have
      previously shown that hemozoin may directly inhibit erythroid development in
      vitro and the levels of hemozoin in plasma from patients with malarial anemia and
      hemozoin within the bone marrow was associated with reduced reticulocyte
      response. We hypothesized that macrophages may reduce, not enhance, the
      inhibitory effect of hemozoin on erythropoiesis. In an in vitro model of
      erythropoiesis, we now show that inhibition of erythroid cell development by
      hemozoin isolated from P. falciparum is characterised by delayed expression of
      the erythroid markers and increased apoptosis of progenitor cells. Crucially,
      macrophages appear to protect erythroid cells from hemozoin, consistent with a
      direct contribution of hemozoin to the depression of reticulocyte output from the
      bone marrow in children with malarial anemia. Moreover, hemozoin isolated from P.
      falciparum in vitro inhibits erythroid development independently of inflammatory
      mediators by inducing apoptotic pathways that not only involve activation of
      caspase 8 and cleavage of caspase 3 but also loss of mitochondrial potential.
      Taken together these data are consistent with a direct effect of hemozoin in
      inducing apoptosis in developing erythroid cells in malarial anemia. Accumulation
      of hemozoin in the bone marrow could therefore result in inadequate
      reticulocytosis in children that have adequate levels of circulating
      erythropoietin.

PMID- 20041182
TI  - The calpain, caspase 12, caspase 3 cascade leading to apoptosis is altered in
      F508del-CFTR expressing cells.
AB  - In cystic fibrosis (CF), the most frequent mutant variant of the cystic fibrosis
      transmembrane conductance regulator (CFTR), F508del-CFTR protein, is misfolded
      and retained in the endoplasmic reticulum (ER). We previously showed that the
      unfolded protein response (UPR) may be triggered in CF. Since prolonged UPR
      activation leads to apoptosis via the calcium-calpain-caspase-12-caspase-3
      cascade and because apoptosis is altered in CF, our aim was to compare the ER
      stress-induced apoptosis pathway between wild type (Wt) and F508del-CFTR
      expressing cells. Here we show that the calcium-calpain-caspase-12-caspase-3
      cascade is altered in F508del-CFTR expressing cells. We propose that this
      alteration is involved in the altered apoptosis triggering observed in CF.

PMID- 20041183
TI  - CCL2 responses to Mycobacterium tuberculosis are associated with disease severity
      in tuberculosis.
AB  - BACKGROUND: Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8
      together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a
      central role in the restriction of M. tuberculosis infections, but is unclear
      whether these markers are indicative of tuberculosis disease severity.
      METHODOLOGY: We investigated live M. tuberculosis- and M. bovis BCG-induced
      peripheral blood mononuclear cell responses in patients with tuberculosis (TB)
      and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB,
      n = 34) and extrapulmonary groups, subdivided into those with less severe
      localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n
      = 16). Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2,
      TNFalpha, CCL3 and CXCL8 were determined. RESULTS: M. tuberculosis- and BCG
      induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05,
      p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M.
      tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups.
      M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p
      = 0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005)
      patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p =
      0.04), while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB
      patients (p = 0.036). TNFalpha mRNA expression was raised in PTB as compared with
      L-ETB group in response to M. tuberculosis (p = 0.02) and BCG (p = 0.03).
      Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups.
      CONCLUSIONS: The increased CCL2 and TNFalpha in PTB patients may support
      effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is
      associated with severity of TB, possibly due to increased systemic inflammation
      found in severe disseminated TB or due to increased monocyte infiltration to lung
      parenchyma in pulmonary disease.

PMID- 20041184
TI  - Age at puberty and the emerging obesity epidemic.
AB  - BACKGROUND: Recent studies have shown that puberty starts at younger ages than
      previously. It has been hypothesized that the increasing prevalence of childhood
      obesity is contributing to this trend. The purpose of this study was to analyze
      the association between prepubertal body mass index (BMI) and pubertal timing, as
      assessed by age at onset of pubertal growth spurt (OGS) and at peak height
      velocity (PHV), and the secular trend of pubertal timing given the prepubertal
      BMI. METHODOLOGY/PRINCIPAL FINDINGS: Annual measurements of height and weight
      were available in all children born from 1930 to 1969 who attended primary school
      in the Copenhagen municipality; 156,835 children fulfilled the criteria for
      determining age at OGS and PHV. The effect of prepubertal BMI at age seven on
      these markers of pubertal development within and between birth cohorts was
      analyzed. BMI at seven years was significantly inversely associated with age at
      OGS and PHV. Dividing the children into five levels of prepubertal BMI, we found
      a similar secular trend toward earlier maturation in all BMI groups.
      CONCLUSION/SIGNIFICANCE: The heavier both boys and girls were at age seven, the
      earlier they entered puberty. Irrespective of level of BMI at age seven, there
      was a downward trend in the age at attaining puberty in both boys and girls,
      which suggests that the obesity epidemic is not solely responsible for the trend.

PMID- 20041185
TI  - Fiber mediated receptor masking in non-infected bystander cells restricts
      adenovirus cell killing effect but promotes adenovirus host co-existence.
AB  - The basic concept of conditionally replicating adenoviruses (CRAD) as oncolytic
      agents is that progenies generated from each round of infection will disperse,
      infect and kill new cancer cells. However, CRAD has only inhibited, but not
      eradicated tumor growth in xenograft tumor therapy, and CRAD therapy has had only
      marginal clinical benefit to cancer patients. Here, we found that CRAD
      propagation and cancer cell survival co-existed for long periods of time when
      infection was initiated at low multiplicity of infection (MOI), and cancer cell
      killing was inefficient and slow compared to the assumed cell killing effect upon
      infection at high MOI. Excessive production of fiber molecules from initial CRAD
      infection of only 1 to 2% cancer cells and their release prior to the viral
      particle itself caused a tropism-specific receptor masking in both infected and
      non-infected bystander cells. Consequently, the non-infected bystander cells were
      inefficiently bound and infected by CRAD progenies. Further, fiber overproduction
      with concomitant restriction of adenovirus spread was observed in xenograft
      cancer therapy models. Besides the CAR-binding Ad4, Ad5, and Ad37, infection with
      CD46-binding Ad35 and Ad11 also caused receptor masking. Fiber overproduction and
      its resulting receptor masking thus play a key role in limiting CRAD
      functionality, but potentially promote adenovirus and host cell co-existence.
      These findings also give important clues for understanding mechanisms underlying
      the natural infection course of various adenoviruses.

PMID- 20041186
TI  - A direct phenotypic comparison of siRNA pools and multiple individual duplexes in
      a functional assay.
AB  - BACKGROUND: RNAi is a prominent tool for the identification of novel regulatory
      elements within complex cellular pathways. In invertebrates, RNAi is a relatively
      straightforward process, where large double-stranded RNA molecules initiate
      sequence-specific transcript destruction in target cells. In contrast, RNAi in
      mammalian cell culture assays requires the delivery of short interfering RNA
      duplexes to target cells. Due to concerns over off-target phenotypes and extreme
      variability in duplex efficiency, investigators typically deliver and analyze
      multiple duplexes per target. Currently, duplexes are delivered and analyzed
      either individually or as a pool of several independent duplexes. A choice
      between experiments based on siRNA pools or multiple individual duplexes has
      considerable implications for throughput, reagent requirements and data analysis
      in genome-wide surveys, yet there are relatively few data that directly compare
      the efficiency of the two approaches. METHODOLOGY/PRINCIPAL FINDINGS: To address
      this critical issue, we conducted a direct comparison of siRNA pools and multiple
      single siRNAs that target all human phosphatases in a robust functional assay. We
      determined the frequency with which both approaches uncover loss-of-function
      phenotypes and compared the phenotypic severity for siRNA pools and the
      constituent individual duplexes. CONCLUSIONS/SIGNIFICANCE: Our survey indicates
      that screens with siRNA pools have several significant advantages over identical
      screens with the corresponding individual siRNA duplexes. Of note, we frequently
      observed greater phenotypic penetrance for siRNA pools than for the parental
      individual duplexes. Thus, our data indicate that experiments with siRNA pools
      have a greater likelihood of generating loss-of-function phenotypes than
      individual siRNA duplexes.

PMID- 20041187
TI  - IL-2 regulates SEB induced toxic shock syndrome in BALB/c mice.
AB  - BACKGROUND: Toxic Shock Syndrome (TSS) is characterized by fever, rash,
      hypotension, constitutional symptoms, and multi-organ involvement and is caused
      by Staphylococcus aureus enterotoxins such as Staphylococcal Enterotoxin B (SEB).
      SEB binds to the MHC-IIalpha chain and is recognized by the TCRbeta chain of the
      Vbeta8 TCR(+) T cells. The binding of SEB to Vbeta chain results in rapid
      activation of T cells and production of inflammatory cytokines, such as
      Interleukin-2 (IL-2), Interferon-gamma and Tumor Necrosis Factor-alpha which
      mediate TSS. Although IL2 was originally identified as the T cell growth factor
      and was proposed to contribute to T cell differentiation, its role in TSS remains
      unexplored. METHODOLOGY/PRINCIPAL FINDINGS: Mice were injected with D-Gal (25
      mg/mouse). One hour after D-Galactosamine (D-Gal) injection each mouse was
      injected with SEB (20 microg/mouse. Mice were then observed for 72 hrs and death
      was recorded at different times. We tested Interleukin-12, IFNgamma, and IL-2
      deficient mice (IL-2(-/-)), but only the IL-2 deficient mice were resistant to
      SEB induced toxic shock syndrome. More importantly reconstitution of IL-2 in IL-2
      deficient mice restored the shock. Interestingly, SEB induced IL-2 production
      from T cells was dependent on p38MAPK activation in macrophages as inhibition of
      it in macrophages significantly inhibited IL-2 production from T cells.
      CONCLUSION: This study shows the importance of IL -2 in TSS which has not been
      previously explored and it also shows that regulating macrophages function can
      regulate T cells and TSS.

PMID- 20041188
TI  - CX3CR1 is expressed by human B lymphocytes and mediates [corrected] CX3CL1 driven
      chemotaxis of tonsil centrocytes.
AB  - BACKGROUND: Fractalkine/CX(3)CL1, a surface chemokine, binds to CX(3)CR1
      expressed by different lymphocyte subsets. Since CX(3)CL1 has been detected in
      the germinal centres of secondary lymphoid tissue, in this study we have
      investigated CX(3)CR1 expression and function in human naive, germinal centre and
      memory B cells isolated from tonsil or peripheral blood. METHODOLOGY/PRINCIPAL
      FINDINGS: We demonstrate unambiguously that highly purified human B cells from
      tonsil and peripheral blood expressed CX(3)CR1 at mRNA and protein levels as
      assessed by quantitative PCR, flow cytometry and competition binding assays. In
      particular, naive, germinal centre and memory B cells expressed CX(3)CR1 but only
      germinal centre B cells were attracted by soluble CX(3)CL1 in a transwell assay.
      CX(3)CL1 signalling in germinal centre B cells involved PI3K, Erk1/2, p38, and
      Src phosphorylation, as assessed by Western blot experiments. CX(3)CR1(+)
      germinal centre B cells were devoid of centroblasts and enriched for centrocytes
      that migrated to soluble CX(3)CL1. ELISA assay showed that soluble CX(3)CL1 was
      secreted constitutively by follicular dendritic cells and T follicular helper
      cells, two cell populations homing in the germinal centre light zone as
      centrocytes. At variance with that observed in humans, soluble CX(3)CL1 did not
      attract spleen B cells from wild type mice. OVA immunized CX(3)CR1(-/-) or
      CX(3)CL1(-/-) mice showed significantly decreased specific IgG production
      compared to wild type mice. CONCLUSION/SIGNIFICANCE: We propose a model whereby
      human follicular dendritic cells and T follicular helper cells release in the
      light zone of germinal centre soluble CX(3)CL1 that attracts centrocytes. The
      functional implications of these results warrant further investigation.

PMID- 20041189
TI  - Anti-dsDNA antibodies promote initiation, and acquired loss of renal Dnase1
      promotes progression of lupus nephritis in autoimmune (NZBxNZW)F1 mice.
AB  - BACKGROUND: Lupus nephritis is characterized by deposition of chromatin fragment
      IgG complexes in the mesangial matrix and glomerular basement membranes (GBM).
      The latter defines end-stage disease. METHODOLOGY/PRINCIPALS: In the present
      study we determined the impact of antibodies to dsDNA, renal Dnase1 and matrix
      metalloprotease (MMP) mRNA levels and enzyme activities on early and late events
      in murine lupus nephritis. The major focus was to analyse if these factors were
      interrelated, and if changes in their expression explain basic processes
      accounting for lupus nephritis. FINDINGS: Early phases of nephritis were
      associated with chromatin-IgG complex deposition in the mesangial matrix. A
      striking observation was that this event correlated with appearance of anti-dsDNA
      antibodies and mild or clinically silent nephritis. These events preceded down
      regulation of renal Dnase1. Later, renal Dnase1 mRNA level and enzyme activity
      were reduced, while MMP2 mRNA level and enzyme activity increased. Reduced levels
      of renal Dnase1 were associated in time with deficient fragmentation of chromatin
      from dead cells. Large fragments were retained and accumulated in GBM. Also,
      since chromatin fragments are prone to stimulate Toll-like receptors in e.g.
      dendritic cells, this may in fact explain increased expression of MMPs.
      SIGNIFICANCE: These scenarios may explain the basis for deposition of chromatin
      IgG complexes in glomeruli in early and late stages of nephritis, loss of
      glomerular integrity and finally renal failure.

PMID- 20041190
TI  - Chylomicrons promote intestinal absorption and systemic dissemination of dietary
      antigen (ovalbumin) in mice.
AB  - BACKGROUND: A small fraction of dietary protein survives enzymatic degradation
      and is absorbed in potentially antigenic form. This can trigger inflammatory
      responses in patients with celiac disease or food allergies, but typically
      induces systemic immunological tolerance (oral tolerance). At present it is not
      clear how dietary antigens are absorbed. Most food staples, including those with
      common antigens such as peanuts, eggs, and milk, contain long-chain triglycerides
      (LCT), which stimulate mesenteric lymph flux and postprandial transport of
      chylomicrons through mesenteric lymph nodes (MLN) and blood. Most dietary
      antigens, like ovalbumin (OVA), are emulsifiers, predicting affinity for
      chylomicrons. We hypothesized that chylomicron formation promotes intestinal
      absorption and systemic dissemination of dietary antigens. METHODOLOGY/PRINCIPAL
      FINDINGS: Absorption of OVA into MLN and blood was significantly enhanced when
      OVA was gavaged into fasted mice together with LCT compared with medium-chain
      triglycerides (MCT), which do not stimulate chylomicron formation. The effect of
      LCT was blocked by the addition of an inhibitor of chylomicron secretion,
      Pluronic L-81. Adoptively transferred OVA-specific DO11.10 T-cells proliferated
      more extensively in peripheral lymph nodes when OVA was gavaged with LCT than
      with MCT or LCT plus Pluronic L-81, suggesting that dietary OVA is systemically
      disseminated. Most dietary OVA in plasma was associated with chylomicrons,
      suggesting that these particles mediate systemic antigen dissemination.
      Intestinal-epithelial CaCo-2 cells secreted more cell-associated, exogenous OVA
      when stimulated with oleic-acid than with butyric acid, and the secreted OVA
      appeared to be associated with chylomicrons. CONCLUSIONS/SIGNIFICANCE:
      Postprandial chylomicron formation profoundly affects absorption and systemic
      dissemination of dietary antigens. The fat content of a meal may affect immune
      responses to dietary antigens by modulating antigen absorption and transport.

PMID- 20041191
TI  - Covariation of branch lengths in phylogenies of functionally related genes.
AB  - Recent studies have shown evidence for the coevolution of functionally-related
      genes. This coevolution is a result of constraints to maintain functional
      relationships between interacting proteins. The studies have focused on the
      correlation in gene tree branch lengths of proteins that are directly interacting
      with each other. We here hypothesize that the correlation in branch lengths is
      not limited only to proteins that directly interact, but also to proteins that
      operate within the same pathway. Using generalized linear models as a basis of
      identifying correlation, we attempted to predict the gene ontology (GO) terms of
      a gene based on its gene tree branch lengths. We applied our method to a dataset
      consisting of proteins from ten prokaryotic species. We found that the degree of
      accuracy to which we could predict the function of the proteins from their gene
      tree varied substantially with different GO terms. In particular, our model could
      accurately predict genes involved in translation and certain ribosomal activities
      with the area of the receiver-operator curve of up to 92%. Further analysis
      showed that the similarity between the trees of genes labeled with similar GO
      terms was not limited to genes that physically interacted, but also extended to
      genes functioning within the same pathway. We discuss the relevance of our
      findings as it relates to the use of phylogenetic methods in comparative
      genomics.

PMID- 20041192
TI  - Identification of beta-secretase (BACE1) substrates using quantitative
      proteomics.
AB  - Beta-site APP cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease with
      a lumenal active site that sheds the ectodomains of membrane proteins through
      juxtamembrane proteolysis. BACE1 has been studied principally for its role in
      Alzheimer's disease as the beta-secretase responsible for generating the amyloid
      beta protein. Emerging evidence from mouse models has identified the importance
      of BACE1 in myelination and cognitive performance. However, the substrates that
      BACE1 processes to regulate these functions are unknown, and to date only a few
      beta-secretase substrates have been identified through candidate-based studies.
      Using an unbiased approach to substrate identification, we performed quantitative
      proteomic analysis of two human epithelial cell lines stably expressing BACE1 and
      identified 68 putative beta-secretase substrates, a number of which we validated
      in a cell culture system. The vast majority were of type I transmembrane
      topology, although one was type II and three were GPI-linked proteins.
      Intriguingly, a preponderance of these proteins are involved in contact-dependent
      intercellular communication or serve as receptors and have recognized roles in
      the nervous system and other organs. No consistent sequence motif predicting
      BACE1 cleavage was identified in substrates versus non-substrates. These findings
      expand our understanding of the proteins and cellular processes that BACE1 may
      regulate, and suggest possible mechanisms of toxicity arising from chronic BACE1
      inhibition.

PMID- 20041193
TI  - Severe obesity in young women and reproductive health: the Danish National Birth
      Cohort.
AB  - BACKGROUND: Little is known about reproductive health in severely obese women. In
      this study, we present associations between different levels of severe obesity
      and a wide range of health outcomes in the mother and child. METHODS: From the
      Danish National Birth Cohort, we obtained self-reported information about
      prepregnant body mass index (BMI) for 2451 severely obese women and 2450 randomly
      selected women from the remaining cohort who served as a comparison group.
      Information about maternal and infant outcomes was also self-reported or came
      from registers. Logistic regression was used to estimate the association between
      different levels of severe obesity and reproductive outcomes. PRINCIPAL FINDINGS:
      Subfecundity was more frequent in severely obese women, and during pregnancy,
      they had an excess risk of urinary tract infections, gestational diabetes,
      preeclampsia and other hypertensive disorders which increased with severity of
      obesity. They tended to have a higher risk of both pre- and post-term birth, and
      risk of cesarean and instrumental deliveries increased across obesity categories.
      After birth, severely obese women more often failed to initiate or sustain
      breastfeeding. Risk of weight retention 1.5 years after birth was similar to that
      of other women, but after adjustment for gestational weight gain, the risk was
      increased, especially in women in the lowest obesity category. In infants,
      increasing maternal obesity was associated with decreased risk of a low birth
      weight and increased risk of a high birth weight. Estimates for ponderal index
      showed the same pattern indicating an increasing risk of neonatal fatness with
      severity of obesity. Infant obesity measured one year after birth was also
      increased in children of severely obese mothers. CONCLUSION: Severe obesity is
      correlated with a substantial disease burden in reproductive health. Although the
      causal mechanisms remain elusive, these findings are useful for making
      predictions and planning health care at the individual level.

PMID- 20041194
TI  - Contrasting patterns of transposable element insertions in Drosophila heat-shock
      promoters.
AB  - The proximal promoter regions of heat-shock genes harbor a remarkable number of P
      transposable element (TE) insertions relative to both positive and negative
      control proximal promoter regions in natural populations of Drosophila
      melanogaster. We have screened the sequenced genomes of 12 species of Drosophila
      to test whether this pattern is unique to these populations. In the 12 species'
      genomes, transposable element insertions are no more abundant in promoter regions
      of single-copy heat-shock genes than in promoters with similar or dissimilar
      architecture. Also, insertions appear randomly distributed across the promoter
      region, whereas insertions clustered near the transcription start site in
      promoters of single-copy heat-shock genes in D. melanogaster natural populations.
      Hsp70 promoters exhibit more TE insertions per promoter than all other genesets
      in the 12 species, similarly to in natural populations of D. melanogaster.
      Insertions in the Hsp70 promoter region, however, cluster away from the
      transcription start site in the 12 species, but near it in natural populations of
      D. melanogaster. These results suggest that D. melanogaster heat-shock promoters
      are unique in terms of their interaction with transposable elements, and confirm
      that Hsp70 promoters are distinctive in TE insertions across Drosophila.

PMID- 20041195
TI  - The function of cortactin in the clustering of acetylcholine receptors at the
      vertebrate neuromuscular junction.
AB  - BACKGROUND: Postsynaptic enrichment of acetylcholine receptors (AChRs) at the
      vertebrate neuromuscular junction (NMJ) depends on the activation of the muscle
      receptor tyrosine MuSK by neural agrin. Agrin-stimulation of MuSK is known to
      initiate an intracellular signaling cascade that leads to the clustering of AChRs
      in an actin polymerization-dependent manner, but the molecular steps which link
      MuSK activation to AChR aggregation remain incompletely defined.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study we used biochemical, cell
      biological and molecular assays to investigate a possible role in AChR clustering
      of cortactin, a protein which is a tyrosine kinase substrate and a regulator of F
      actin assembly and which has also been previously localized at AChR clustering
      sites. We report that cortactin was co-enriched at AChR clusters in situ with its
      target the Arp2/3 complex, which is a key stimulator of actin polymerization in
      cells. Cortactin was further preferentially tyrosine phosphorylated at AChR
      clustering sites and treatment of myotubes with agrin significantly enhanced the
      tyrosine phosphorylation of cortactin. Importantly, forced expression in myotubes
      of a tyrosine phosphorylation-defective cortactin mutant (but not wild-type
      cortactin) suppressed agrin-dependent AChR clustering, as did the reduction of
      endogenous cortactin levels using RNA interference, and introduction of the
      mutant cortactin into muscle cells potently inhibited synaptic AChR aggregation
      in response to innervation. CONCLUSION: Our results suggest a novel function of
      phosphorylation-dependent cortactin signaling downstream from agrin/MuSK in
      facilitating AChR clustering at the developing NMJ.

PMID- 20041196
TI  - Increased expression and protein divergence in duplicate genes is associated with
      morphological diversification.
AB  - The differentiation of both gene expression and protein function is thought to be
      important as a mechanism of the functionalization of duplicate genes. However, it
      has not been addressed whether expression or protein divergence of duplicate
      genes is greater in those genes that have undergone functionalization compared
      with those that have not. We examined a total of 492 paralogous gene pairs
      associated with morphological diversification in a plant model organism
      (Arabidopsis thaliana). Classifying these paralogous gene pairs into high, low,
      and no morphological diversification groups, based on knock-out data, we found
      that the divergence rate of both gene expression and protein sequences were
      significantly higher in either high or low morphological diversification groups
      compared with those in the no morphological diversification group. These results
      strongly suggest that the divergence of both expression and protein sequence are
      important sources for morphological diversification of duplicate genes. Although
      both mechanisms are not mutually exclusive, our analysis suggested that changes
      of expression pattern play the minor role (33%-41%) and that changes of protein
      sequence play the major role (59%-67%) in morphological diversification. Finally,
      we examined to what extent duplicate genes are associated with expression or
      protein divergence exerting morphological diversification at the whole-genome
      level. Interestingly, duplicate genes randomly chosen from A. thaliana had not
      experienced expression or protein divergence that resulted in morphological
      diversification. These results indicate that most duplicate genes have
      experienced minor functionalization.

PMID- 20041197
TI  - Genome-wide association data reveal a global map of genetic interactions among
      protein complexes.
AB  - This work demonstrates how gene association studies can be analyzed to map a
      global landscape of genetic interactions among protein complexes and pathways.
      Despite the immense potential of gene association studies, they have been
      challenging to analyze because most traits are complex, involving the combined
      effect of mutations at many different genes. Due to lack of statistical power,
      only the strongest single markers are typically identified. Here, we present an
      integrative approach that greatly increases power through marker clustering and
      projection of marker interactions within and across protein complexes. Applied to
      a recent gene association study in yeast, this approach identifies 2,023 genetic
      interactions which map to 208 functional interactions among protein complexes. We
      show that such interactions are analogous to interactions derived through reverse
      genetic screens and that they provide coverage in areas not yet tested by reverse
      genetic analysis. This work has the potential to transform gene association
      studies, by elevating the analysis from the level of individual markers to global
      maps of genetic interactions. As proof of principle, we use synthetic genetic
      screens to confirm numerous novel genetic interactions for the INO80 chromatin
      remodeling complex.

PMID- 20041199
TI  - Reply to: Austin et al. CytoJournal 2009;6:12 (Unfounded claims mar scientific
      critique).

PMID- 20041198
TI  - The Bifidobacterium dentium Bd1 genome sequence reflects its genetic adaptation
      to the human oral cavity.
AB  - Bifidobacteria, one of the relatively dominant components of the human intestinal
      microbiota, are considered one of the key groups of beneficial intestinal
      bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the
      genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic
      cariogenic pathogen. The genetic basis for the ability of B. dentium to survive
      in the oral cavity and contribute to caries development is not understood. The
      genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to
      completion to uncover a single circular 2,636,368 base pair chromosome with 2,143
      predicted open reading frames. Annotation of the genome sequence revealed
      multiple ways in which B. dentium has adapted to the oral environment through
      specialized nutrient acquisition, defences against antimicrobials, and gene
      products that increase fitness and competitiveness within the oral niche. B.
      dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent
      with genome-based predictions, while colonization and persistence factors
      implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva
      derived compounds were also identified. Global transcriptome analysis
      demonstrated that many of the genes encoding these predicted traits are highly
      expressed under relevant physiological conditions. This is the first report to
      identify, through various genomic approaches, specific genetic adaptations of a
      Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a
      cariogenic microorganism in the oral cavity. In silico analysis and comparative
      genomic hybridization experiments clearly reveal a high level of genome
      conservation among various B. dentium strains. The data indicate that the genome
      of this opportunistic cariogen has evolved through a very limited number of
      horizontal gene acquisition events, highlighting the narrow boundaries that
      separate commensals from opportunistic pathogens.

PMID- 20041200
TI  - Bistability of mitochondrial respiration underlies paradoxical reactive oxygen
      species generation induced by anoxia.
AB  - Increased production of reactive oxygen species (ROS) in mitochondria underlies
      major systemic diseases, and this clinical problem stimulates a great scientific
      interest in the mechanism of ROS generation. However, the mechanism of hypoxia
      induced change in ROS production is not fully understood. To mathematically
      analyze this mechanism in details, taking into consideration all the possible
      redox states formed in the process of electron transport, even for respiratory
      complex III, a system of hundreds of differential equations must be constructed.
      Aimed to facilitate such tasks, we developed a new methodology of modeling, which
      resides in the automated construction of large sets of differential equations.
      The detailed modeling of electron transport in mitochondria allowed for the
      identification of two steady state modes of operation (bistability) of
      respiratory complex III at the same microenvironmental conditions. Various
      perturbations could induce the transition of respiratory chain from one steady
      state to another. While normally complex III is in a low ROS producing mode,
      temporal anoxia could switch it to a high ROS producing state, which persists
      after the return to normal oxygen supply. This prediction, which we qualitatively
      validated experimentally, explains the mechanism of anoxia-induced cell damage.
      Recognition of bistability of complex III operation may enable novel therapeutic
      strategies for oxidative stress and our method of modeling could be widely used
      in systems biology studies.

PMID- 20041201
TI  - A constant light-genetic screen identifies KISMET as a regulator of circadian
      photoresponses.
AB  - Circadian pacemakers are essential to synchronize animal physiology and behavior
      with the dayrationight cycle. They are self-sustained, but the phase of their
      oscillations is determined by environmental cues, particularly light intensity
      and temperature cycles. In Drosophila, light is primarily detected by a dedicated
      blue-light photoreceptor: CRYPTOCHROME (CRY). Upon light activation, CRY binds to
      the pacemaker protein TIMELESS (TIM) and triggers its proteasomal degradation,
      thus resetting the circadian pacemaker. To understand further the CRY input
      pathway, we conducted a misexpression screen under constant light based on the
      observation that flies with a disruption in the CRY input pathway remain robustly
      rhythmic instead of becoming behaviorally arrhythmic. We report the
      identification of more than 20 potential regulators of CRY-dependent light
      responses. We demonstrate that one of them, the chromatin-remodeling enzyme
      KISMET (KIS), is necessary for normal circadian photoresponses, but does not
      affect the circadian pacemaker. KIS genetically interacts with CRY and functions
      in PDF-negative circadian neurons, which play an important role in circadian
      light responses. It also affects daily CRY-dependent TIM oscillations in a
      peripheral tissue: the eyes. We therefore conclude that KIS is a key
      transcriptional regulator of genes that function in the CRY signaling cascade,
      and thus it plays an important role in the synchronization of circadian rhythms
      with the dayrationight cycle.

PMID- 20041202
TI  - Rational mutational analysis of a multidrug MFS transporter CaMdr1p of Candida
      albicans by employing a membrane environment based computational approach.
AB  - CaMdr1p is a multidrug MFS transporter of pathogenic Candida albicans. An over
      expression of the gene encoding this protein is linked to clinically encountered
      azole resistance. In-depth knowledge of the structure and function of CaMdr1p is
      necessary for an effective design of modulators or inhibitors of this efflux
      transporter. Towards this goal, in this study, we have employed a membrane
      environment based computational approach to predict the functionally critical
      residues of CaMdr1p. For this, information theoretic scores which are variants of
      Relative Entropy (Modified Relative Entropy RE(M)) were calculated from Multiple
      Sequence Alignment (MSA) by separately considering distinct physico-chemical
      properties of transmembrane (TM) and inter-TM regions. The residues of CaMdr1p
      with high RE(M) which were predicted to be significantly important were subjected
      to site-directed mutational analysis. Interestingly, heterologous host
      Saccharomyces cerevisiae, over-expressing these mutant variants of CaMdr1p
      wherein these high RE(M) residues were replaced by either alanine or leucine,
      demonstrated increased susceptibility to tested drugs. The hypersensitivity to
      drugs was supported by abrogated substrate efflux mediated by mutant variant
      proteins and was not attributed to their poor expression or surface localization.
      Additionally, by employing a distance plot from a 3D deduced model of CaMdr1p, we
      could also predict the role of these functionally critical residues in
      maintaining apparent inter-helical interactions to provide the desired fold for
      the proper functioning of CaMdr1p. Residues predicted to be critical for function
      across the family were also found to be vital from other previously published
      studies, implying its wider application to other membrane protein families.

PMID- 20041203
TI  - Feedback inhibition in the PhoQ/PhoP signaling system by a membrane peptide.
AB  - The PhoQ/PhoP signaling system responds to low magnesium and the presence of
      certain cationic antimicrobial peptides. It regulates genes important for growth
      under these conditions, as well as additional genes important for virulence in
      many gram-negative pathogens. PhoQ is a sensor kinase that phosphorylates and
      activates the transcription factor PhoP. Since feedback inhibition is a common
      theme in stress-response circuits, we hypothesized that some members of the PhoP
      regulon may play such a role in the PhoQ/PhoP pathway. We therefore screened for
      PhoP-regulated genes that mediate feedback in this system. We found that deletion
      of mgrB (yobG), which encodes a 47 amino acid peptide, results in a potent
      increase in PhoP-regulated transcription. In addition, over-expression of mgrB
      decreased transcription at both high and low concentrations of magnesium.
      Localization and bacterial two-hybrid studies suggest that MgrB resides in the
      inner-membrane and interacts directly with PhoQ. We further show that MgrB
      homologs from Salmonella typhimurium and Yersinia pestis also repress PhoP
      regulated transcription in these organisms. In cell regulatory circuits, feedback
      has been associated with modulating the induction kinetics and/or the cell-to
      cell variability in response to stimulus. Interestingly, we found that
      elimination of MgrB-mediated feedback did not have a significant effect on the
      kinetics of reporter protein production and did not decrease the variability in
      expression among cells. Our results indicate MgrB is a broadly conserved membrane
      peptide that is a critical mediator of negative feedback in the PhoQ/PhoP
      circuit. This new regulator may function as a point of control that integrates
      additional input signals to modulate the activity of this important signaling
      system.

PMID- 20041204
TI  - A stochastic model for microtubule motors describes the in vivo cytoplasmic
      transport of human adenovirus.
AB  - Cytoplasmic transport of organelles, nucleic acids and proteins on microtubules
      is usually bidirectional with dynein and kinesin motors mediating the delivery of
      cargoes in the cytoplasm. Here we combine live cell microscopy, single virus
      tracking and trajectory segmentation to systematically identify the parameters of
      a stochastic computational model of cargo transport by molecular motors on
      microtubules. The model parameters are identified using an evolutionary
      optimization algorithm to minimize the Kullback-Leibler divergence between the in
      silico and the in vivo run length and velocity distributions of the viruses on
      microtubules. The present stochastic model suggests that bidirectional transport
      of human adenoviruses can be explained without explicit motor coordination. The
      model enables the prediction of the number of motors active on the viral cargo
      during microtubule-dependent motions as well as the number of motor binding
      sites, with the protein hexon as the binding site for the motors.

PMID- 20041205
TI  - Bayesian integration and non-linear feedback control in a full-body motor task.
AB  - A large number of experiments have asked to what degree human reaching movements
      can be understood as being close to optimal in a statistical sense. However,
      little is known about whether these principles are relevant for other classes of
      movements. Here we analyzed movement in a task that is similar to surfing or
      snowboarding. Human subjects stand on a force plate that measures their center of
      pressure. This center of pressure affects the acceleration of a cursor that is
      displayed in a noisy fashion (as a cloud of dots) on a projection screen while
      the subject is incentivized to keep the cursor close to a fixed position. We find
      that salient aspects of observed behavior are well-described by optimal control
      models where a Bayesian estimation model (Kalman filter) is combined with an
      optimal controller (either a Linear-Quadratic-Regulator or Bang-bang controller).
      We find evidence that subjects integrate information over time taking into
      account uncertainty. However, behavior in this continuous steering task appears
      to be a highly non-linear function of the visual feedback. While the nervous
      system appears to implement Bayes-like mechanisms for a full-body, dynamic task,
      it may additionally take into account the specific costs and constraints of the
      task.

PMID- 20041206
TI  - Design principles for ligand-sensing, conformation-switching ribozymes.
AB  - Nucleic acid sensor elements are proving increasingly useful in biotechnology and
      biomedical applications. A number of ligand-sensing, conformational-switching
      ribozymes (also known as allosteric ribozymes or aptazymes) have been generated
      by some combination of directed evolution or rational design. Such sensor
      elements typically fuse a molecular recognition domain (aptamer) with a catalytic
      signal generator (ribozyme). Although the rational design of aptazymes has begun
      to be explored, the relationships between the thermodynamics of aptazyme
      conformational changes and aptazyme performance in vitro and in vivo have not
      been examined in a quantitative framework. We have therefore developed a
      quantitative and predictive model for aptazymes as biosensors in vitro and as
      riboswitches in vivo. In the process, we have identified key relationships (or
      dimensionless parameters) that dictate aptazyme performance, and in consequence,
      established equations for precisely engineering aptazyme function. In particular,
      our analysis quantifies the intrinsic trade-off between ligand sensitivity and
      the dynamic range of activity. We were also able to determine how in vivo
      parameters, such as mRNA degradation rates, impact the design and function of
      aptazymes when used as riboswitches. Using this theoretical framework we were
      able to achieve quantitative agreement between our models and published data. In
      consequence, we are able to suggest experimental guidelines for quantitatively
      predicting the performance of aptazyme-based riboswitches. By identifying factors
      that limit the performance of previously published systems we were able to
      generate immediately testable hypotheses for their improvement. The robust
      theoretical framework and identified optimization parameters should now enable
      the precision design of aptazymes for biotechnological and clinical applications.

PMID- 20041207
TI  - Burst-time-dependent plasticity robustly guides ON/OFF segregation in the lateral
      geniculate nucleus.
AB  - Spontaneous retinal activity (known as "waves") remodels synaptic connectivity to
      the lateral geniculate nucleus (LGN) during development. Analysis of retinal
      waves recorded with multielectrode arrays in mouse suggested that a cue for the
      segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs)
      in the LGN may be a desynchronization in their firing, where ON cells precede OFF
      cells by one second. Using the recorded retinal waves as input, with two
      different modeling approaches we explore timing-based plasticity rules for the
      evolution of synaptic weights to identify key features underlying ON/OFF
      segregation. First, we analytically derive a linear model for the evolution of ON
      and OFF weights, to understand how synaptic plasticity rules extract input firing
      properties to guide segregation. Second, we simulate postsynaptic activity with a
      nonlinear integrate-and-fire model to compare findings with the linear model. We
      find that spike-time-dependent plasticity, which modifies synaptic weights based
      on millisecond-long timing and order of pre- and postsynaptic spikes, fails to
      segregate ON and OFF retinal inputs in the absence of normalization. Implementing
      homeostatic mechanisms results in segregation, but only with carefully-tuned
      parameters. Furthermore, extending spike integration timescales to match the
      second-long input correlation timescales always leads to ON segregation because
      ON cells fire before OFF cells. We show that burst-time-dependent plasticity can
      robustly guide ON/OFF segregation in the LGN without normalization, by
      integrating pre- and postsynaptic bursts irrespective of their firing order and
      over second-long timescales. We predict that an LGN neuron will become ON- or OFF
      responsive based on a local competition of the firing patterns of neighboring
      RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF
      segregation in ferret, despite differences in the firing properties of retinal
      waves. Our model suggests that diverse input statistics of retinal waves can be
      robustly interpreted by a burst-based rule, which underlies retinogeniculate
      plasticity across different species.

PMID- 20041208
TI  - Tradeoff between stability and multispecificity in the design of promiscuous
      proteins.
AB  - Natural proteins often partake in several highly specific protein-protein
      interactions. They are thus subject to multiple opposing forces during
      evolutionary selection. To be functional, such multispecific proteins need to be
      stable in complex with each interaction partner, and, at the same time, to
      maintain affinity toward all partners. How is this multispecificity acquired
      through natural evolution? To answer this compelling question, we study a
      prototypical multispecific protein, calmodulin (CaM), which has evolved to
      interact with hundreds of target proteins. Starting from high-resolution
      structures of sixteen CaM-target complexes, we employ state-of-the-art
      computational methods to predict a hundred CaM sequences best suited for
      interaction with each individual CaM target. Then, we design CaM sequences most
      compatible with each possible combination of two, three, and all sixteen targets
      simultaneously, producing almost 70,000 low energy CaM sequences. By comparing
      these sequences and their energies, we gain insight into how nature has managed
      to find the compromise between the need for favorable interaction energies and
      the need for multispecificity. We observe that designing for more partners
      simultaneously yields CaM sequences that better match natural sequence profiles,
      thus emphasizing the importance of such strategies in nature. Furthermore, we
      show that the CaM binding interface can be nicely partitioned into positions that
      are critical for the affinity of all CaM-target complexes and those that are
      molded to provide interaction specificity. We reveal several basic categories of
      sequence-level tradeoffs that enable the compromise necessary for the promiscuity
      of this protein. We also thoroughly quantify the tradeoff between interaction
      energetics and multispecificity and find that facilitating seemingly competing
      interactions requires only a small deviation from optimal energies. We conclude
      that multispecific proteins have been subjected to a rigorous optimization
      process that has fine-tuned their sequences for interactions with a precise set
      of targets, thus conferring their multiple cellular functions.

PMID- 20041209
TI  - The presence of VEGF receptors on the luminal surface of endothelial cells
      affects VEGF distribution and VEGF signaling.
AB  - Vascular endothelial growth factor (VEGF) is a potent cytokine that binds to
      specific receptors on the endothelial cells lining blood vessels. The signaling
      cascade triggered eventually leads to the formation of new capillaries, a process
      called angiogenesis. Distributions of VEGF receptors and VEGF ligands are
      therefore crucial determinants of angiogenic events and, to our knowledge, no
      quantification of abluminal vs. luminal receptors has been performed. We
      formulate a molecular-based compartment model to investigate the VEGF
      distribution in blood and tissue in humans and show that such quantification
      would lead to new insights on angiogenesis and VEGF-dependent diseases. Our
      multiscale model includes two major isoforms of VEGF (VEGF(121) and VEGF(165)),
      as well as their receptors (VEGFR1 and VEGFR2) and the non-signaling co-receptor
      neuropilin-1 (NRP1). VEGF can be transported between tissue and blood via
      transendothelial permeability and the lymphatics. VEGF receptors are located on
      both the luminal and abluminal sides of the endothelial cells. In this study, we
      analyze the effects of the VEGF receptor localization on the endothelial cells as
      well as of the lymphatic transport. We show that the VEGF distribution is
      affected by the luminal receptor density. We predict that the receptor signaling
      occurs mostly on the abluminal endothelial surface, assuming that VEGF is
      secreted by parenchymal cells. However, for a low abluminal but high luminal
      receptor density, VEGF binds predominantly to VEGFR1 on the abluminal surface and
      VEGFR2 on the luminal surface. Such findings would be pertinent to pathological
      conditions and therapies related to VEGF receptor imbalance and overexpression on
      the endothelial cells and will hopefully encourage experimental receptor
      quantification for both luminal and abluminal surfaces on endothelial cells.

PMID- 20041210
TI  - A phenotypic profile of the Candida albicans regulatory network.
AB  - Candida albicans is a normal resident of the gastrointestinal tract and also the
      most prevalent fungal pathogen of humans. It last shared a common ancestor with
      the model yeast Saccharomyces cerevisiae over 300 million years ago. We describe
      a collection of 143 genetically matched strains of C. albicans, each of which has
      been deleted for a specific transcriptional regulator. This collection represents
      a large fraction of the non-essential transcription circuitry. A phenotypic
      profile for each mutant was developed using a screen of 55 growth conditions. The
      results identify the biological roles of many individual transcriptional
      regulators; for many, this work represents the first description of their
      functions. For example, a quarter of the strains showed altered colony formation,
      a phenotype reflecting transitions among yeast, pseudohyphal, and hyphal cell
      forms. These transitions, which have been closely linked to pathogenesis, have
      been extensively studied, yet our work nearly doubles the number of
      transcriptional regulators known to influence them. As a second example, nearly a
      quarter of the knockout strains affected sensitivity to commonly used antifungal
      drugs; although a few transcriptional regulators have previously been implicated
      in susceptibility to these drugs, our work indicates many additional mechanisms
      of sensitivity and resistance. Finally, our results inform how transcriptional
      networks evolve. Comparison with the existing S. cerevisiae data (supplemented by
      additional S. cerevisiae experiments reported here) allows the first systematic
      analysis of phenotypic conservation by orthologous transcriptional regulators
      over a large evolutionary distance. We find that, despite the many specific
      wiring changes documented between these species, the general phenotypes of
      orthologous transcriptional regulator knockouts are largely conserved. These
      observations support the idea that many wiring changes affect the detailed
      architecture of the circuit, but not its overall output.

PMID- 20041211
TI  - Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a
      conserved polyubiquitination machinery within macrophages and protozoa.
AB  - The ability of Legionella pneumophila to proliferate within various protozoa in
      the aquatic environment and in macrophages indicates a remarkable evolution and
      microbial exploitation of evolutionarily conserved eukaryotic processes. Ankyrin
      B (AnkB) of L. pneumophila is a non-canonical F-box-containing protein, and is
      the only known Dot/Icm-translocated effector of L. pneumophila essential for
      intra-vacuolar proliferation within both macrophages and protozoan hosts. We show
      that the F-box domain of AnkB and the (9)L(10)P conserved residues are essential
      for intracellular bacterial proliferation and for rapid acquisition of
      polyubiquitinated proteins by the Legionella-containing vacuole (LCV) within
      macrophages, Dictyostelium discoideum, and Acanthamoeba. Interestingly,
      translocation of AnkB and recruitment of polyubiquitinated proteins in
      macrophages and Acanthamoeba is rapidly triggered by extracellular bacteria
      within 5 min of bacterial attachment. Ectopically expressed AnkB within mammalian
      cells is localized to the periphery of the cell where it co-localizes with host
      SKP1 and recruits polyubiquitinated proteins, which results in restoration of
      intracellular growth to the ankB mutant similar to the parental strain. While an
      ectopically expressed AnkB-(9)L(10)P/AA variant is localized to the cell
      periphery, it does not recruit polyubiquitinated proteins and fails to trans
      rescue the ankB mutant intracellular growth defect. Direct in vivo interaction of
      AnkB but not the AnkB-(9)L(10)P/AA variant with the host SKP1 is demonstrated.
      Importantly, RNAi-mediated silencing of expression of SKP1 renders the cells non
      permissive for intracellular proliferation of L. pneumophila. The role of AnkB in
      exploitation of the polyubiquitination machinery is essential for intrapulmonary
      bacterial proliferation in the mouse model of Legionnaires' disease. Therefore,
      AnkB exhibits a novel molecular and functional mimicry of eukaryotic F-box
      proteins that exploits conserved polyubiquitination machinery for intracellular
      proliferation within evolutionarily distant hosts.

PMID- 20041212
TI  - Expanding the paradigms of plant pathogen life history and evolution of parasitic
      fitness beyond agricultural boundaries.

PMID- 20041213
TI  - Chemokine coreceptor signaling in HIV-1 infection and pathogenesis.
AB  - Binding of the HIV-1 envelope to its chemokine coreceptors mediates two major
      biological events: membrane fusion and signaling transduction. The fusion process
      has been well studied, yet the role of chemokine coreceptor signaling in viral
      infection has remained elusive through the past decade. With the recent
      demonstration of the signaling requirement for HIV latent infection of resting
      CD4 T cells, the issue of coreceptor signaling needs to be thoroughly revisited.
      It is likely that virus-mediated signaling events may facilitate infection in
      various immunologic settings in vivo where cellular conditions need to be primed;
      in other words, HIV may exploit the chemokine signaling network shared among
      immune cells to gain access to downstream cellular components, which can then
      serve as effective tools to break cellular barriers. This virus-hijacked aberrant
      signaling process may in turn facilitate pathogenesis. In this review, we
      summarize past and present studies on HIV coreceptor signaling. We also discuss
      possible roles of coreceptor signaling in facilitating viral infection and
      pathogenesis.

PMID- 20041215
TI  - Decomposition of gene expression state space trajectories.
AB  - Representing and analyzing complex networks remains a roadblock to creating
      dynamic network models of biological processes and pathways. The study of cell
      fate transitions can reveal much about the transcriptional regulatory programs
      that underlie these phenotypic changes and give rise to the coordinated patterns
      in expression changes that we observe. The application of gene expression state
      space trajectories to capture cell fate transitions at the genome-wide level is
      one approach currently used in the literature. In this paper, we analyze the gene
      expression dataset of Huang et al. (2005) which follows the differentiation of
      promyelocytes into neutrophil-like cells in the presence of inducers dimethyl
      sulfoxide and all-trans retinoic acid. Huang et al. (2005) build on the work of
      Kauffman (2004) who raised the attractor hypothesis, stating that cells exist in
      an expression landscape and their expression trajectories converge towards
      attractive sites in this landscape. We propose an alternative interpretation that
      explains this convergent behavior by recognizing that there are two types of
      processes participating in these cell fate transitions-core processes that
      include the specific differentiation pathways of promyelocytes to neutrophils,
      and transient processes that capture those pathways and responses specific to the
      inducer. Using functional enrichment analyses, specific biological examples and
      an analysis of the trajectories and their core and transient components we
      provide a validation of our hypothesis using the Huang et al. (2005) dataset.

PMID- 20041214
TI  - RNA interference and single particle tracking analysis of hepatitis C virus
      endocytosis.
AB  - Hepatitis C virus (HCV) enters hepatocytes following a complex set of receptor
      interactions, culminating in internalization via clathrin-mediated endocytosis.
      However, aside from receptors, little is known about the cellular molecular
      requirements for infectious HCV entry. Therefore, we analyzed a siRNA library
      that targets 140 cellular membrane trafficking genes to identify host genes
      required for infectious HCV production and HCV pseudoparticle entry. This
      approach identified 16 host cofactors of HCV entry that function primarily in
      clathrin-mediated endocytosis, including components of the clathrin endocytosis
      machinery, actin polymerization, receptor internalization and sorting, and
      endosomal acidification. We next developed single particle tracking analysis of
      highly infectious fluorescent HCV particles to examine the co-trafficking of HCV
      virions with cellular cofactors of endocytosis. We observe multiple, sequential
      interactions of HCV virions with the actin cytoskeleton, including retraction
      along filopodia, actin nucleation during internalization, and migration of
      internalized particles along actin stress fibers. HCV co-localizes with clathrin
      and the ubiquitin ligase c-Cbl prior to internalization. Entering HCV particles
      are associated with the receptor molecules CD81 and the tight junction protein,
      claudin-1; however, HCV-claudin-1 interactions were not restricted to Huh-7.5
      cell-cell junctions. Surprisingly, HCV internalization generally occurred outside
      of Huh-7.5 cell-cell junctions, which may reflect the poorly polarized nature of
      current HCV cell culture models. Following internalization, HCV particles
      transport with GFP-Rab5a positive endosomes, which is consistent with trafficking
      to the early endosome. This study presents technical advances for imaging HCV
      entry, in addition to identifying new host cofactors of HCV infection, some of
      which may be antiviral targets.

PMID- 20041216
TI  - Comparative ICE genomics: insights into the evolution of the SXT/R391 family of
      ICEs.
AB  - Integrating and conjugative elements (ICEs) are one of the three principal types
      of self-transmissible mobile genetic elements in bacteria. ICEs, like plasmids,
      transfer via conjugation; but unlike plasmids and similar to many phages, these
      elements integrate into and replicate along with the host chromosome. Members of
      the SXT/R391 family of ICEs have been isolated from several species of gram
      negative bacteria, including Vibrio cholerae, the cause of cholera, where they
      have been important vectors for disseminating genes conferring resistance to
      antibiotics. Here we developed a plasmid-based system to capture and isolate
      SXT/R391 ICEs for sequencing. Comparative analyses of the genomes of 13 SXT/R391
      ICEs derived from diverse hosts and locations revealed that they contain 52
      perfectly syntenic and nearly identical core genes that serve as a scaffold
      capable of mobilizing an array of variable DNA. Furthermore, selection pressure
      to maintain ICE mobility appears to have restricted insertions of variable DNA
      into intergenic sites that do not interrupt core functions. The variable genes
      confer diverse element-specific phenotypes, such as resistance to antibiotics.
      Functional analysis of a set of deletion mutants revealed that less than half of
      the conserved core genes are required for ICE mobility; the functions of most of
      the dispensable core genes are unknown. Several lines of evidence suggest that
      there has been extensive recombination between SXT/R391 ICEs, resulting in re
      assortment of their respective variable gene content. Furthermore, our analyses
      suggest that there may be a network of phylogenetic relationships among sequences
      found in all types of mobile genetic elements.

PMID- 20041217
TI  - TGF-beta Sma/Mab signaling mutations uncouple reproductive aging from somatic
      aging.
AB  - Female reproductive cessation is one of the earliest age-related declines humans
      experience, occurring in mid-adulthood. Similarly, Caenorhabditis elegans'
      reproductive span is short relative to its total life span, with reproduction
      ceasing about a third into its 15-20 day adulthood. All of the known mutations
      and treatments that extend C. elegans' reproductive period also regulate
      longevity, suggesting that reproductive span is normally linked to life span. C.
      elegans has two canonical TGF-beta signaling pathways. We recently found that the
      TGF-beta Dauer pathway regulates longevity through the Insulin/IGF-1 Signaling
      (IIS) pathway; here we show that this pathway has a moderate effect on
      reproductive span. By contrast, TGF-beta Sma/Mab signaling mutants exhibit a
      substantially extended reproductive period, more than doubling reproductive span
      in some cases. Sma/Mab mutations extend reproductive span disproportionately to
      life span and act independently of known regulators of somatic aging, such as
      Insulin/IGF-1 Signaling and Dietary Restriction. This is the first discovery of a
      pathway that regulates reproductive span independently of longevity and the first
      identification of the TGF-beta Sma/Mab pathway as a regulator of reproductive
      aging. Our results suggest that longevity and reproductive span regulation can be
      uncoupled, although they appear to normally be linked through regulatory
      pathways.

PMID- 20041218
TI  - Progressive Purkinje cell degeneration in tambaleante mutant mice is a
      consequence of a missense mutation in HERC1 E3 ubiquitin ligase.
AB  - The HERC gene family encodes proteins with two characteristic domains: HECT and
      RCC1-like. Proteins with HECT domains have been described to function as
      ubiquitin ligases, and those that contain RCC1-like domains have been reported to
      function as GTPases regulators. These two activities are essential in a number of
      important cellular processes such as cell cycle, cell signaling, and membrane
      trafficking. Mutations affecting these domains have been found associated with
      retinitis pigmentosa, amyotrophic lateral sclerosis, and cancer. In humans, six
      HERC genes have been reported which encode two subgroups of HERC proteins: large
      (HERC1-2) and small (HERC3-6). The giant HERC1 protein was the first to be
      identified. It has been involved in membrane trafficking and cell
      proliferation/growth through its interactions with clathrin, M2-pyruvate kinase,
      and TSC2 proteins. Mutations affecting other members of the HERC family have been
      found to be associated with sterility and growth retardation. Here, we report the
      characterization of a recessive mutation named tambaleante, which causes
      progressive Purkinje cell degeneration leading to severe ataxia with reduced
      growth and lifespan in homozygous mice aged over two months. We mapped this
      mutation in mouse chromosome 9 and then performed positional cloning. We found a
      G<-->A transition at position 1448, causing a Gly to Glu substitution (Gly483Glu)
      in the highly conserved N-terminal RCC1-like domain of the HERC1 protein.
      Successful transgenic rescue, with either a mouse BAC containing the normal copy
      of Herc1 or with the human HERC1 cDNA, validated our findings. Histological and
      biochemical studies revealed extensive autophagy associated with an increase of
      the mutant protein level and a decrease of mTOR activity. Our observations
      concerning this first mutation in the Herc1 gene contribute to the functional
      annotation of the encoded E3 ubiquitin ligase and underline the crucial and
      unexpected role of this protein in Purkinje cell physiology.

PMID- 20041219
TI  - Biomedical text mining and its applications.

PMID- 20041220
TI  - Autoimmune disease classification by inverse association with SNP alleles.
AB  - With multiple genome-wide association studies (GWAS) performed across autoimmune
      diseases, there is a great opportunity to study the homogeneity of genetic
      architectures across autoimmune disease. Previous approaches have been limited in
      the scope of their analysis and have failed to properly incorporate the direction
      of allele-specific disease associations for SNPs. In this work, we refine the
      notion of a genetic variation profile for a given disease to capture strength of
      association with multiple SNPs in an allele-specific fashion. We apply this
      method to compare genetic variation profiles of six autoimmune diseases: multiple
      sclerosis (MS), ankylosing spondylitis (AS), autoimmune thyroid disease (ATD),
      rheumatoid arthritis (RA), Crohn's disease (CD), and type 1 diabetes (T1D), as
      well as five non-autoimmune diseases. We quantify pair-wise relationships between
      these diseases and find two broad clusters of autoimmune disease where SNPs that
      make an individual susceptible to one class of autoimmune disease also protect
      from diseases in the other autoimmune class. We find that RA and AS form one such
      class, and MS and ATD another. We identify specific SNPs and genes with opposite
      risk profiles for these two classes. We furthermore explore individual SNPs that
      play an important role in defining similarities and differences between disease
      pairs. We present a novel, systematic, cross-platform approach to identify allele
      specific relationships between disease pairs based on genetic variation as well
      as the individual SNPs which drive the relationships. While recognizing
      similarities between diseases might lead to identifying novel treatment options,
      detecting differences between diseases previously thought to be similar may point
      to key novel disease-specific genes and pathways.

PMID- 20041221
TI  - A quick guide for developing effective bioinformatics programming skills.

PMID- 20041222
TI  - Analysis of FOXP3+ regulatory T cells that display apparent viral antigen
      specificity during chronic hepatitis C virus infection.
AB  - We reported previously that a proportion of natural CD25(+) cells isolated from
      the PBMC of HCV patients can further upregulate CD25 expression in response to
      HCV peptide stimulation in vitro, and proposed that virus-specific regulatory T
      cells (Treg) were primed and expanded during the disease. Here we describe
      epigenetic analysis of the FOXP3 locus in HCV-responsive natural CD25(+) cells
      and show that these cells are not activated conventional T cells expressing
      FOXP3, but hard-wired Treg with a stable FOXP3 phenotype and function. Of
      approximately 46,000 genes analyzed in genome wide transcription profiling, about
      1% were differentially expressed between HCV-responsive Treg, HCV-non-responsive
      natural CD25(+) cells and conventional T cells. Expression profiles, including
      cell death, activation, proliferation and transcriptional regulation, suggest a
      survival advantage of HCV-responsive Treg over the other cell populations. Since
      no Treg-specific activation marker is known, we tested 97 NS3-derived peptides
      for their ability to elicit CD25 response (assuming it is a surrogate marker),
      accompanied by high resolution HLA typing of the patients. Some reactive peptides
      overlapped with previously described effector T cell epitopes. Our data offers
      new insights into HCV immune evasion and tolerance, and highlights the non-self
      specific nature of Treg during infection.

PMID- 20041223
TI  - Identification of amino acids in HA and PB2 critical for the transmission of H5N1
      avian influenza viruses in a mammalian host.
AB  - Since 2003, H5N1 influenza viruses have caused over 400 known cases of human
      infection with a mortality rate greater than 60%. Most of these cases resulted
      from direct contact with virus-contaminated poultry or poultry products. Although
      only limited human-to-human transmission has been reported to date, it is feared
      that efficient human-to-human transmission of H5N1 viruses has the potential to
      cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral
      transmission among humans is largely unknown. In this study, we used guinea pigs
      as a mammalian model to study the transmission of six different H5N1 avian
      influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35)
      and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated
      animals to naive contact animals. Our mutagenesis analysis revealed that the
      amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite
      for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the
      hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at
      158-160, was responsible for HA binding to sialylated glycans and was critical
      for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and
      HA could serve as important molecular markers for assessing the pandemic
      potential of H5N1 field isolates.

PMID- 20041224
TI  - The human retinoblastoma gene is imprinted.
AB  - Genomic imprinting is an epigenetic process leading to parent-of-origin-specific
      DNA methylation and gene expression. To date, approximately 60 imprinted human
      genes are known. Based on genome-wide methylation analysis of a patient with
      multiple imprinting defects, we have identified a differentially methylated CpG
      island in intron 2 of the retinoblastoma (RB1) gene on chromosome 13. The CpG
      island is part of a 5'-truncated, processed pseudogene derived from the KIAA0649
      gene on chromosome 9 and corresponds to two small CpG islands in the open reading
      frame of the ancestral gene. It is methylated on the maternal chromosome 13 and
      acts as a weak promoter for an alternative RB1 transcript on the paternal
      chromosome 13. In four other KIAA0649 pseudogene copies, which are located on
      chromosome 22, the two CpG islands have deteriorated and the CpG dinucleotides
      are fully methylated. By analysing allelic RB1 transcript levels in blood cells,
      as well as in hypermethylated and 5-aza-2'-deoxycytidine-treated lymphoblastoid
      cells, we have found that differential methylation of the CpG island skews RB1
      gene expression in favor of the maternal allele. Thus, RB1 is imprinted in the
      same direction as CDKN1C, which operates upstream of RB1. The imprinting of two
      components of the same pathway indicates that there has been strong evolutionary
      selection for maternal inhibition of cell proliferation.

PMID- 20041226
TI  - Identification and mapping of the leaf stripe resistance gene Rdg1a in Hordeum
      spontaneum.
AB  - Leaf stripe of barley, caused by Pyrenophora graminea, is an important seed-borne
      disease in organically grown as well as in conventionally grown Nordic and
      Mediterranean barley districts. Two barley segregating populations represented by
      103 recombinant inbred lines (RILs) of the cross L94 (susceptible) x Vada
      (resistant) and 194 RILs of the cross Arta (susceptible) x Hordeum spontaneum 41
      1 (resistant) were analysed with two highly virulent leaf stripe isolates, Dg2
      and Dg5, to identify loci for P. graminea resistance. A major gene with its
      positive allele contributed by Vada and H. spontaneum 41-1 was detected in both
      populations and for both pathogen isolates on chromosome 2HL explaining 44.1 and
      91.8% R (2), respectively for Dg2 and Dg5 in L94 x Vada and 97.8 and 96.1% R (2),
      respectively for Dg2 and Dg5 in Arta x H. spontaneum 41-1. Common markers in the
      gene region of the two populations enabled map comparison and highlighted an
      overlapping for the region of the resistance locus. Since the map position of the
      resistance locus identified in this report is the same as that for the leaf
      stripe resistance gene Rdg1a, mapped earlier in Alf and derived from the
      'botanical' barley line H. laevigatum, we propose that leaf stripe resistance in
      Vada and H. spontaneum 41-1 is governed by the same gene, namely by Rdg1a, and
      that Rdg1a resistance could be traced back to H. spontaneum, the progenitor of
      cultivated barley. PCR-based molecular markers that can be used for marker
      assisted selection (MAS) of Rdg1a were identified. An Rdg1a syntenic interval
      with the rice chromosome arm 4L was identified on the basis of rice orthologs of
      EST-based barley markers. Analysis of the rice genes annotated into the syntenic
      interval did not reveal sequences strictly belonging to the major class
      (nucleotide-binding site plus leucine-rich repeat) of the resistance genes.
      Nonetheless, four genes coding for domains that are present in the major disease
      resistance genes, namely receptor-like protein kinase and ATP/GTP-binding
      proteins, were identified together with a homolog of the barley powdery mildew
      resistance gene mlo. Three (out of five) homologs of these genes were mapped in
      the Rdg1a region in barley and the mlo homolog map position was tightly
      associated with the LOD score peak in both populations.

PMID- 20041227
TI  - Evolution of particulate matter and associated metal levels in the urban area of
      Rio de Janeiro, Brazil.
AB  - The levels of total suspended particles and airborne particulate trace metals
      were determined in three locations. Two of these locations are in the
      metropolitan area of Rio de Janeiro, where the main source of pollution is
      vehicular traffic. The remaining location is in a suburban area characterized by
      industrial and vehicular emissions, as well as natural input. Enrichment factors
      found in the downtown area for Zn, Cu, Pb and Cd were in the interval 21-3237,
      indicating an important contribution of anthropogenic sources. In the suburban
      area, Zn levels were unusually high (596.8-5475.4 ng m(-3)) and may be attributed
      to the proximity of a company that produces lubricants and lubricant additives.

PMID- 20041225
TI  - Bacterial effector binding to ribosomal protein s3 subverts NF-kappaB function.
AB  - Enteric bacterial pathogens cause food borne disease, which constitutes an
      enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC)
      causes a severe bloody diarrhea following transmission to humans through various
      means, including contaminated beef and vegetable products, water, or through
      contact with animals. EHEC also causes a potentially fatal kidney disease
      (hemolytic uremic syndrome) for which there is no effective treatment or
      prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli
      (EPEC), Salmonella, Shigella, Yersinia) utilize a type III secretion system
      (T3SS) to inject virulence proteins (effectors) into host cells. While it is
      known that T3SS effectors subvert host cell function to promote diarrheal disease
      and bacterial transmission, in many cases, the mechanisms by which these
      effectors bind to host proteins and disrupt the normal function of intestinal
      epithelial cells have not been completely characterized. In this study, we
      present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS
      effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of
      nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the
      cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2
      was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are
      autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is
      independent of kinase activity. NleH1, but not NleH2, reduced the nuclear
      abundance of RPS3 without altering the p50 or p65 NF-kappaB subunits or affecting
      the phosphorylation state or abundance of the inhibitory NF-kappaB chaperone
      IkappaBalpha NleH1 repressed the transcription of a RPS3/NF-kappaB-dependent
      reporter plasmid, but did not inhibit the transcription of RPS3-independent
      reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well as
      an AP-1-dependent reporter. We identified a region of NleH1 (N40-K45) that is at
      least partially responsible for the inhibitory activity of NleH1 toward RPS3.
      Deleting nleH1 from E. coli O157:H7 produced a hypervirulent phenotype in a
      gnotobiotic piglet model of Shiga toxin-producing E. coli infection. We suggest
      that NleH may disrupt host innate immune responses by binding to a cofactor of
      host transcriptional complexes.

PMID- 20041228
TI  - Polybrominated diphenyl ethers (PBDEs) concentration in sediments located in the
      vicinity of fish plant effluent outfalls in the maritimes.
AB  - Since polybrominated biphenyl ethers (PBDEs) are known to be present in various
      species of fish, it is likely that fish processing effluent would contain
      significant amount of PBDEs. The purpose of this study was to determine the PBDE
      concentrations in sediments located near fish plant effluent outfalls. The range
      of concentrations of PBDEs in marine sediments in Canada published in the
      literature was very similar to the results obtained in this study (0.015-5.12
      ng/g, dry weight). The concentrations measured in this study for all three
      technical mixtures (2.78 x 10(-3), 1.92 x 10(-3) and 2.02 x 10(-3) mg/kg,
      respectively) were all below known toxicity thresholds (0.031, 9.1 and 76 mg/kg,
      respectively).

PMID- 20041230
TI  - Quartz crystal microbalance, a valuable tool for elucidation of interactions
      between apoB-100 peptides and extracellular matrix components.
AB  - Atherosclerosis has received wide attention as a primary cause of premature death
      in developed countries. The retention of low-density lipoprotein (LDL) particles
      in the intima, the inner layer of the capillaries, has been imputed as the main
      cause of the development of atherosclerotic plaques. The entrapment of LDL is
      mainly due to the specific interaction between the lysine-rich site on
      apolipoprotein B-100 (apoB-100), a major apolipoprotein of LDL, and extracellular
      matrix (ECM) components such as collagen, proteoglycans, and glycosaminoglycans
      (GAGs). Although valuable techniques already exist for studies on apoB-100 and
      ECM interactions, there is continued need for miniaturized tools that can
      complement the tools already available and even provide totally new data. This
      work explores the applicability of the quartz crystal microbalance (QCM) for
      interaction studies between apoB-100 peptide fragments and various components of
      the ECM. Two positive peptide fragments, PP and PP(2), and two components of the
      ECM, collagen I and a selected GAG, chondroitin 6-sulfate (C6S), were immobilized
      on polystyrene and carboxyl sensor chips. C6S was injected as analyte for PP- and
      PP(2)-coated surfaces, while PP was the analyte for collagen I and C(6)S
      surfaces. The estimated dissociation constant (K(D)) indicates that the
      interactions occur via the positive residues, lysine and arginine, of apoB-100.
      The continuous-flow QCM system employed in this study is shown to be an excellent
      tool for the elucidation of interactions between these types of biomolecules.

PMID- 20041229
TI  - Chronic clozapine treatment improves prenatal infection-induced working memory
      deficits without influencing adult hippocampal neurogenesis.
AB  - BACKGROUND: Converging evidence indicates that prenatal exposure to immune
      challenge can induce long-term cognitive deficits relevant to schizophrenia. Such
      cognitive impairments may be related to deficient hippocampal neurogenesis at
      adult age. OBJECTIVES: In the present study, we sought evidence for the
      possibility that chronic treatment with the reference atypical antipsychotic drug
      clozapine may improve prenatal infection-induced cognitive dysfunctions by
      stimulating adult hippocampal neurogenesis. METHODS: This hypothesis was tested
      in a well-established mouse model of prenatal immune challenge which is based on
      prenatal administration of the viral mimic, polyriboinosinic-polyribocytidilic
      acid (PolyI:C). RESULTS: We found that maternal PolyI:C (5 mg/kg, i.v.) exposure
      on gestation day 17 led to significant spatial working memory impairment and
      reduced hippocampal neurogenesis in the resulting offspring at adult age. The
      latter effect was apparent in postmortem immunohistochemical analyses of the cell
      proliferation marker bromodeoxyuridine and the microtubule-associated protein
      doublecortin, a marker of newborn neuronal cells. Chronic (3 weeks)
      administration of clozapine (5 mg/kg/day, i.p.) significantly improved the
      prenatal PolyI:C-induced working memory deficits, while at the same time, it
      negatively affected working memory performance in adult offspring born to control
      mothers. These bidirectional cognitive effects of clozapine were not paralleled
      by concomitant effects on adult hippocampal neurogenesis. CONCLUSIONS: Our
      findings do not support the hypothesis that the atypical antipsychotic drug
      clozapine may influence cognitive functions by acting on adult neurogenesis in
      the hippocampus, regardless of whether the drug is administered to subjects with
      or without a neurodevelopmental predisposition to adult neuropathology.

PMID- 20041231
TI  - Evaluation of quantum dots applied as switchable layer in a light-controlled
      electrochemical sensor.
AB  - Gold electrodes with switchable conductance are created by coating the gold
      surface with different colloidal quantum dots. For the quantum dot
      immobilization, a dithiol compound was used. By polarizing the electrode and
      applying a light pointer, local photocurrents were generated. The performance of
      this setup was characterized for a variety of different nanoparticle materials
      regarding drift and signal-to-noise ratio. We varied the following parameters:
      quantum dot materials and immobilization protocol. The results indicate that the
      performance of the sensor strongly depends on how the quantum dots are bound to
      the gold electrode. The best results were obtained by inclusion of an additional
      polyelectrolyte film, which had been fabricated using layer-by-layer assembly.

PMID- 20041232
TI  - Seeing all the obstacles in your way: the effect of visual feedback and visual
      feedback schedule on obstacle avoidance while reaching.
AB  - Human reaching behaviour displays sophisticated obstacle avoidance. Recently, we
      demonstrated that the obstacle avoidance system in normal participants is
      sensitive to both the position and size of obstacles (Chapman and Goodale in Exp
      Brain Res 191:83-97, 2008). A limitation in this previous study was that reaches
      were performed without visual feedback, and were not made to a specific target
      (i.e. the target was a long strip instead of a point). Many studies have shown
      that both the introduction of visual feedback and the order in which the feedback
      is presented (visual feedback schedule) significantly alter performance in simple
      visuomotor tasks (Zelaznik et al. in J Mot Behav 15:217-236, 1983). Thus, the
      present study was designed to compare obstacle avoidance when reaches were made
      to a discrete target with vision (V) and with no vision (NV) under different
      three visual feedback schedules (blocked, random, and alternating). Twenty-four
      right-handed participants performed reaches in the presence of one, two, or no
      obstacles placed mid-reach. In addition to replicating previous work with
      reaching without vision, we showed that robust avoidance behaviour occurred when
      reaches were made to a specific target, when reaching with only one object
      present, and, critically, when vision of the hand was available during the reach.
      Moreover, the visual feedback schedule also had a significant effect on several
      kinematic measures--but only on the NV trials. That is, regardless of its
      predictability or recent availability, vision was used in the same way for all
      reaches. In contrast, performance on blocked-NV trials was markedly different
      from performance on NV trials presented under random or alternating schedules. In
      addition to extending our understanding of obstacle avoidance during reaching,
      our results suggest that, in a complex and more natural reach-to-point task, the
      human visuomotor system is optimized to use visual feedback.

PMID- 20041233
TI  - Goal anticipation during action observation is influenced by synonymous action
      capabilities, a puzzling developmental study.
AB  - Eighteen- and 25-month-old human toddlers' ability to manually solve a puzzle and
      their ability to anticipate the goal during observation of similar actions were
      investigated. Results demonstrate that goal anticipation during action
      observation is dependent on manual ability, both on a group level (only 25-month
      olds solved the manual task and anticipated the goal during observation) and
      individually within the older age group (r (xy) = 0.53). These findings suggests
      a connection between manual ability and the ability to anticipate the goal of
      others' actions in toddlers, in accordance with the direct matching hypothesis.

PMID- 20041234
TI  - Visually mediated eye movements regulate the capture of optic flow in self-motion
      perception.
AB  - Eye movements help capture optic-flow information necessary to perceive visually
      our self motion. Visual and vestibular systems control compensatory eye movements
      that serve to stabilize the retinal images we capture. We examined the role that
      these eye movements may play in generating visual illusions of self motion (or
      vection). Observers viewed radially expanding optic-flow displays while
      performing lateral translational head oscillations at 1 Hz. Simulated viewpoint
      changes in these displays were synchronized with head movements, either in an
      ipsilateral (minimal sensory conflict) or a contralateral (high sensory conflict)
      direction. In control conditions, the observer viewed purely radial displays.
      Vection-onset latency and overall vection strength ratings were recorded, as well
      as horizontal eye movements. Vection onsets and strength ratings were
      significantly greater when the observer's head movements were incorporated into
      the visual displays. However, vection strength ratings were very similar for both
      ipsilateral and contralateral active display oscillation. Surprisingly, the non
      ecological contralateral viewpoint oscillation actually induced vection earlier,
      despite the relatively small eye-in-head rotations coordinating gaze in these
      conditions. Our results support the view that compensatory eye movements are
      controlled through cooperative visual and vestibular interactions, and show that
      linear vection is highly robust against large sensory conflicts.

PMID- 20041235
TI  - Asymmetric perception of radial expansion/contraction in Japanese macaque (Macaca
      fuscata) infants.
AB  - Visual radial expansion/contraction motion provides important visual information
      that is used to control several adaptive actions. We investigated radial motion
      perception in infant Japanese macaque monkeys using an experimental procedure
      previously developed for human infants. We found that the infant monkeys' visual
      preference for the radial expansion pattern was greater than that for the radial
      contraction pattern. This trend towards an "expansion bias" is similar to that
      observed in human infants. These results suggest that asymmetrical radial motion
      processing is a basic visual function common to primates, and that it emerges
      early in life.

PMID- 20041236
TI  - Vestibular and pulse-related modulation of skin sympathetic nerve activity during
      sinusoidal galvanic vestibular stimulation in human subjects.
AB  - We have previously shown that sinusoidal galvanic vestibular stimulation (sGVS),
      a means of a selectively modulating vestibular afferent input without affecting
      other inputs, can cause partial entrainment of muscle sympathetic nerve activity
      (MSNA). Given that motion sickness causes sweating and pallor, we tested the
      hypothesis that sGVS also entrains skin sympathetic nerve activity (SSNA), but
      that the optimal frequencies are closer to those associated with slow postural
      changes (0.2 Hz). SSNA was recorded via tungsten microelectrodes inserted into
      the common peroneal nerve in 11 awake-seated subjects. Bipolar binaural
      sinusoidal GVS (+/-2 mA, 200 cycles) was applied to the mastoid processes at
      frequencies of 0.2, 0.5, 0.8, 1.1, 1.4, 1.7 and 2.0 Hz. All subjects reported
      strong postural illusions of 'rocking in a boat' or 'swaying in a hammock'.
      Sinusoidal GVS caused a marked entrainment of SSNA at all frequencies. Measured
      as the modulation index, vestibular modulation ranged from 81.5 +/- 4.0% at 0.2
      Hz to 76.6 +/- 3.6% at 1.7 Hz; it was significantly weaker at 2.0 Hz (63.2 +/-
      5.4%). Interestingly, pulse-related modulation of SSNA, which is normally weak,
      increased significantly during sGVS but was stronger at 0.8 Hz (86.2 +/- 2.0%)
      than at 0.2 Hz (69.3 +/- 8.3%), the opposite of the pattern seen with vestibular
      modulation of MSNA. We conclude that vestibular inputs can entrain the firing of
      cutaneous sympathetic neurones and increase their normally weak pulse-related
      rhythmicity.

PMID- 20041237
TI  - Serial search for fingers of the same hand but not for fingers of different
      hands.
AB  - In most haptic search tasks, tactile stimuli are presented to the fingers of both
      hands. In such tasks, the search pattern for some object features, such as the
      shape of raised line symbols, has been found to be serial. The question is
      whether this search is serial over all fingers irrespective of the hand, or
      whether it is serial over the fingers of each hand and parallel over the two
      hands. To investigate this issue, we determined the speed of static haptic search
      when two items are presented to two fingers of the same hand and when two items
      are presented to two fingers of different hands. We compared the results with
      predictions for parallel and serial search based on the results of a previous
      study using the same items and a similar task. The results indicate that two
      fingers of the same hand process information in a serial manner, while two
      fingers of two different hands process information in parallel. Thus, considering
      the individual fingers as independent units in haptic search may not be
      justified, because the hand that they belong to matters.

PMID- 20041238
TI  - Regulation of the Ca(2+) channel TRPV6 by the kinases SGK1, PKB/Akt, and PIKfyve.
AB  - The serum- and glucocorticoid-inducible kinase SGK1 and the protein kinase
      PKB/Akt presumably phosphorylate and, by this means, activate the mammalian
      phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3), which has in turn
      been shown to regulate transporters and channels. SGK1-regulated channels include
      the Ca(2+) channel TRPV6, which is expressed in a variety of epithelial and
      nonepithelial cells including tumor cells. SGK1 and protein kinase B PKB/Akt
      foster tumor growth. The present study thus explored whether TRPV6 is regulated
      by PIKfyve. TRPV6 was expressed in Xenopus laevis oocytes with or without
      additional coexpression of constitutively active (S422D)SGK1, constitutively
      active (T308D,S473D)PKB, wild-type PIKfyve, and (S318A)PIKfyve lacking the SGK1
      phosphorylation site. TRPV6 activity was determined from the current (I(Ca))
      resulting from TRPV6-induced Ca(2+) entry and subsequent activation of Ca(2+)
      sensitive endogenous Cl(-) channels. TRPV6 protein abundance in the cell membrane
      was determined utilizing immunohistochemistry and Western blotting. In TRPV6
      expressing oocytes I(H) was increased by coexpression of (S422D)SGK1 and by
      (T308D,S473D)PKB. Coexpression of wild-type PIKfyve further increased I(H) in
      TRPV6 + (S422D)SGK1-expressing oocytes but did not significantly modify I(Ca) in
      oocytes expressing TRPV6 alone. (S318A)PIKfyve failed to significantly modify
      I(Ca) in the presence and absence of (S422D)SGK1. (S422D)SGK1 increased the TRPV6
      protein abundance in the cell membrane, an effect augmented by additional
      expression of wild-type PIKfyve. We conclude that PIKfyve participates in the
      regulation of TRPV6.

PMID- 20041239
TI  - Studying patterns of recent evolution at synonymous sites and intronic sites in
      Drosophila melanogaster.
AB  - Most previous studies of the evolution of codon usage bias (CUB) and intronic GC
      content (iGC) in Drosophila melanogaster were based on between-species
      comparisons, reflecting long-term evolutionary events. However, a complete
      picture of the evolution of CUB and iGC cannot be drawn without knowledge of
      their more recent evolutionary history. Here, we used a polymorphism dataset
      collected from Zimbabwe to study patterns of the recent evolution of CUB and iGC.
      Analyzing coding and intronic data jointly with a model which can simultaneously
      estimate selection, mutational, and demographic parameters, we have found that:
      (1) natural selection is probably acting on synonymous codons; (2) a constant
      population size model seems to be sufficient to explain most of the observed
      synonymous polymorphism patterns; (3) GC is favored over AT in introns. In
      agreement with the long-term evolutionary patterns, ongoing selection acting on X
      linked synonymous codons is stronger than that acting on autosomal codons. The
      selective differences between preferred and unpreferred codons tend to be greater
      than the differences between GC and AT in introns, suggesting that natural
      selection, not just biased gene conversion, may have influenced the evolution of
      CUB. Interestingly, evidence for non-equilibrium evolution comes exclusively from
      the intronic data. However, three different models, an equilibrium model with two
      classes of selected sites and two non-equilibrium models with changes in either
      population size or mutational parameters, fit the intronic data equally well.
      These results show that using inadequate selection (or demographic) models can
      result in incorrect estimates of demographic (or selection) parameters.

PMID- 20041240
TI  - Hitchhiking and the population genetic structure of avian influenza virus.
AB  - Previous studies have revealed a major difference in the phylogenetic structure,
      extent of genetic diversity, and selection pressure between the surface
      glycoproteins and internal gene segments of avian influenza viruses (AIV) sampled
      from wild birds. However, what evolutionary processes are responsible for these
      strikingly different evolutionary patterns is unclear. To address this issue, we
      estimated the rate of evolutionary change and time of origin of each segment of
      AIV sampled globally. Strikingly, the internal segments of the sampled AIV
      strains possess common ancestors that existed less than 200 years ago. Similarly
      recent times of origin were observed for each of the individual subtypes within
      the HA, NA, and NS gene segments. Such a shallow history of genetic diversity
      suggests an evolutionary model in which the genetic structure of AIV is shaped by
      a combination of occasional selective sweeps in the HA and NA (and possibly NS)
      segments, coupled with transient genetic linkage to the internal gene segments.

PMID- 20041241
TI  - Exploring improved endoglucanase expression in Saccharomyces cerevisiae strains.
AB  - The endoglucanase I and II genes (egI or Cel7B and egII or Cel5A) of Trichoderma
      reesei QM6a were successfully cloned and expressed in Saccharomyces cerevisiae
      under the transcriptional control of the yeast ENO1 promoter and terminator
      sequences. Random mutagenesis of the egI-bearing plasmid resulted in a twofold
      increase in extracellular EGI activity. Both endoglucanase genes were co
      expressed with the synthetic, codon-optimised cellobiohydrolase gene (s-cbhI)
      from T. reesei as well as the beta-glucosidase gene (bgl1) from Saccharomycopsis
      fibuligera in S. cerevisiae. Extracellular endoglucanase activity was lower when
      co-expressed with s-cbhI or bgl1. Recombinant strains were able to hydrolyse
      phosphoric acid swollen cellulose, generating mainly cellotriose, cellobiose and
      glucose. Cellobiose accumulated, suggesting the beta-glucosidase activity to be
      the rate-limiting factor. As a consequence, the recombinant strains were unable
      to produce enough glucose for growth on amorphous cellulose. The results of this
      study provide insight into further optimisation of recombinantly expressed
      cellulase combinations for saccharification and fermentation of cellulose to
      ethanol.

PMID- 20041242
TI  - Total shoulder arthroplasty in dislocation arthropathy.
AB  - Follow-up examinations of 45 patients who received shoulder arthroplasty for
      osteoarthritis following shoulder instability were conducted after 44 months. The
      goal of this study was to describe the clinical findings associated with advanced
      glenohumeral arthritis due to shoulder instability and instability repairs and to
      present the clinical results and complications of treating this with shoulder
      arthroplasty. The weighted average Constant score increased significantly from
      49.4 to 81.3 points. There was no significant difference in the type of
      arthroplasty with 35 cases of total shoulder replacements and ten cases of
      hemiarthoplasty. The rate of complications was 40% (18/45 patients) with 20%
      (9/45 patients) requiring an operative revision. Patients with arthritis after
      instability repair showed great improvement in all qualities of the Constant
      score. Nonetheless, further analyses are required to determine why such a
      relatively young group of patients showed high complication rates.

PMID- 20041243
TI  - Oncocytic cell tumors of the thyroid: factors predicting malignancy and
      influencing prognosis, treatment decisions, and outcomes.
AB  - BACKGROUND: The distinction between malignant and benign thyroid oncocytic cell
      tumors (OCTs) before and during surgery still represents a diagnostic challenge.
      We focused on the search for specific factors that predict malignancy and
      influence the prognosis of OCTs, and for their most appropriate management.
      METHODS: From January 1998 to May 2007, 57 patients underwent thyroidectomy in
      our surgical department because of OCT. A cross-sectional study of 28 patients
      with carcinoma and 29 patients with adenoma was performed: demographic data,
      tumor characteristics, diagnostic results, patient management, postoperative, and
      follow-up results were evaluated. RESULTS: The prevalence of malignancy was
      49.1%. The mean tumor size was significantly greater for carcinomas than for
      adenomas (3.0 cm vs. 1.8 cm; p = 0.003). Threshold sizes of more than 3.0 cm and
      4.0 cm were significant for predicting malignancy (p = 0.020 and p = 0.010,
      respectively). Tumor multifocality, microfollicular features, and severe
      cytological atypia also were significantly related to malignancy (p = 0.012 and p
      = 0.025, respectively). Recurrent OCT was observed in three patients with
      carcinoma. One patient with distant metastases died from the disease. Older age,
      tumor size, thyroid capsular invasion, higher TNM stage, and AMES high risk were
      factors significantly related to tumor recurrence. Multivariate analysis showed
      that larger tumor size was the only factor predictive of malignancy and
      influencing recurrence. CONCLUSIONS: All OCTs should be referred to surgery
      because of the high prevalence of malignancy. In the case of OCTs with larger
      tumor size and microfollicular features with severe cytological atypia, total
      thyroidectomy is strongly recommended as initial treatment also in relation with
      the more likely aggressive biological behavior of greater tumors.

PMID- 20041245
TI  - Pancreatic insulinoma: a surgical experience.

PMID- 20041244
TI  - Excellent prognosis of patients with solitary T1N0M0 papillary thyroid carcinoma
      who underwent thyroidectomy and elective lymph node dissection without
      radioiodine therapy.
AB  - BACKGROUND: The extent of surgery for papillary carcinoma significantly differs
      between western countries and Japan. Almost routine total thyroidectomy with
      radioiodine ablation therapy has been performed in western countries, whereas
      limited thyroidectomy has been adopted in Japan, especially for low-risk cases.
      In this study, the prognosis of patients with solitary papillary carcinoma
      measuring 2 cm or less without massive extrathyroid extension, clinically
      apparent lymph node metastasis or distant metastasis at diagnosis (T1N0M0 in the
      UICC TNM classification) was investigated to elucidate the appropriate extent of
      surgery for these patients. METHODS: We investigated the prognosis of 2,638
      patients with solitary T1N0M0 papillary carcinoma who underwent initial surgery
      between 1987 and 2004. Total or near total thyroidectomy was performed for 1,037
      patients and the remaining 1,601 patients underwent more limited thyroidectomy.
      Elective central node dissection was performed for 2,511 patients, accounting for
      96%, and 1,545 (59%) also underwent prophylactic lateral node dissection.
      Radioiodine ablation therapy was performed only for three patients. RESULTS: The
      10-year disease-free survival (DFS) rate of our series was 97%. To date,
      recurrence was observed in 62 patients (2%) and 41 showed recurrence to the
      regional lymph nodes. Seventeen of 1,601 patients who received limited
      thyroidectomy (1%) showed recurrence to the remnant thyroid. Pathological nodal
      positive patients showed a worse DFS, but the 10-year DFS rate was still high at
      96%. Patients with total or near total thyroidectomy had a better DFS, but the
      difference disappeared if recurrence to the remnant thyroid was excluded. A
      number needed to treat (NNT) for total or near total thyroidectomy over
      hemithyroidectomy was 83 to prevent 1 recurrence. CONCLUSIONS: These findings
      suggest that solitary T1N0M0 patients have an excellent prognosis when they
      undergo thyroidectomy and elective lymph node dissection without radioiodine
      therapy. Regarding the extent of thyroidectomy, hemithyroidectomy is adequate for
      these patients, if a 1% risk of recurrence to the remnant thyroid is accepted.

PMID- 20041246
TI  - Pain as the only consistent sign of acute appendicitis: lack of inflammatory
      signs does not exclude the diagnosis.
AB  - BACKGROUND: The clinical diagnosis of acute appendicitis in adults remains
      tricky, but radiological examinations are very helpful to determine the diagnosis
      even when the adult patient presents atypically. This study was designed to
      quantify the proportion of patients with a preoperative diagnosis of acute
      appendicitis that had isolated right lower quadrant pain without biological
      inflammatory signs and then to determine which imaging examination led to the
      determination of the diagnosis. METHODS: In this monocentric study based on
      retrospectively collected data, we analyzed a series of 326 patients with a
      preoperative diagnosis of acute appendicitis and isolated those who were afebrile
      and had isolated right lower quadrant pain and normal white blood cell counts and
      C-reactive protein levels. We determined whether the systematic ultrasonography
      examination was informative enough or a complementary intravenous contrast media
      computed tomography scan was necessary to determine the diagnosis, and whether
      the final pathological diagnosis fit the preoperative one. RESULTS: A total of
      15.6% of the patients with a preoperative diagnosis of acute appendicitis had
      isolated rebound tenderness in the right lower quadrant, i.e., they were afebrile
      and their white blood cell counts and C-reactive protein levels were normal. In
      96.1% of the cases, the ultrasonography examination, sometimes complemented by an
      intravenous contrasted computed tomography scan if the ultrasonography result was
      equivocal, fit the histopathological diagnosis of acute appendicitis.
      CONCLUSIONS: The diagnosis of acute appendicitis cannot be excluded when an adult
      patient presents with isolated rebound tenderness in the right lower quadrant
      even without fever and biological inflammatory signs. In our study,
      ultrasonography and computed tomography were very helpful when making the final
      diagnosis.

PMID- 20041247
TI  - Central lymph node metastasis: is it a reliable indicator of lateral node
      involvement in papillary thyroid carcinoma?
AB  - BACKGROUND: The purpose of the present study was to evaluate the reliability of
      central lymph node metastases in predicting lateral node involvement in papillary
      thyroid carcinoma (PTC). METHODS: This retrospective study consists of 121
      patients with PTC who underwent ipsilateral selective neck dissection. The
      quantitative relationship between central and lateral lymph node metastases (LNM)
      was analyzed. RESULTS: A total of 86 patients (71.1%) had pathologically proven
      LNM; 55 patients had LNM in both the central and lateral compartments, 22
      patients had only central LNM, and 9 patients had skip metastasis to lateral
      nodes. The sensitivity of central node involvement to predict lateral LNM was
      85.9%, the specificity was 61.4%. The presence of two or more positive central
      nodes was associated with a high incidence of lateral LNM (70-93.3%), when
      compared with none (20.5%) or one (47.4%) positive central node. CONCLUSIONS: The
      node status of the central compartment is moderately predictive of that of
      lateral compartment. The presence of two or more positive central nodes may be of
      value in predicting lateral node involvement.

PMID- 20041248
TI  - Expression of vascular endothelial growth factor and presence of angiovascular
      cells in tissues from different thyroid disorders.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is involved in tumor
      angiogenesis and other pathophysiological processes. MATERIALS AND METHODS: We
      studied the localization of VEGF in human thyroid tissues to clarify its
      involvement in proliferative processes in a variety of thyroid disorders.
      Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or
      anti-human CD34 antibody and a streptavidin-biotin peroxidase complex detection
      system was performed on 58 tissue specimens from 53 patients with different
      thyroid disorders and 5 normal thyroid glands. RESULTS: Vascular endothelial
      growth factor was not detected in normal thyroid follicular cells. However, some
      thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18;
      follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11;
      adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter,
      weak expression of VEGF was found in small areas of the tumor, whereas in
      malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF
      was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves'
      disease. Angiovascular cells stained with CD34 antibody in tissues from different
      thyroid disorders reflected statistically significant differences in papillary
      carcinoma, follicular adenoma, and Graves' disease compared with normal thyroids,
      and such cells showed a trend toward increases in medullary carcinoma and
      adenomatous goiter. In contrast, low vascularity was observed in anaplastic
      carcinoma, malignant lymphoma, and follicular carcinoma. CONCLUSIONS: Because
      VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression
      of this mediator, concomitant with hypervascularity, may be induced more strongly
      in malignant thyroid tumors, which need more oxygen to proliferate, than in
      benign follicular tumors. However, neither VEGF nor CD34 was expressed in
      anaplastic thyroid carcinoma, which is an extremely poorly differentiated
      malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid
      tissues of Graves' disease composed of nontransformed cells. Thus, the expression
      of VEGF concomitant with CD34 is suggested to reflect both the transformation and
      differentiation state of malignant tumors.

PMID- 20041249
TI  - Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis.
AB  - BACKGROUND: Antibiotic treatment has been shown to be effective in treating
      selected patients with acute appendicitis, and three randomized controlled trials
      (RCTs) have compared the efficacy of antibiotic therapy alone with that of
      surgery for acute appendicitis. The purpose of this meta-analysis of RCTs was to
      assess the outcomes with these two therapeutic modalities. METHODS: All RCTs
      comparing antibiotic therapy alone with surgery in patients over 18 years of age
      with suspected acute appendicitis were included. Patients with suspected
      perforated appendix or peritonitis, and those with an allergy to antibiotics had
      been excluded in the RCTs. The outcome measures studied were complications,
      length of hospital stay, and readmissions. RESULTS: Meta-analysis of RCTs of
      antibiotic therapy versus surgery showed a trend toward a reduced risk of
      complications in the antibiotic-treated group [RR (95%CI): 0.43 (0.16, 1.18) p =
      0.10], without prolonging the length of hospital stay [mean difference (inverse
      variance, random, 95% CI): 0.11 (-0.22, 0.43) p = 0.53]. Of the 350 patients
      randomized to the antibiotic group, 238 (68%) were treated successfully with
      antibiotics alone and 38 (15%) were readmitted. The remaining 112 (32%) patients
      randomized to antibiotic therapy crossed over to surgery for a variety of
      reasons. At 1 year, 200 patients in the antibiotic group remained asymptomatic.
      CONCLUSIONS: This meta-analysis suggests that although antibiotics may be used as
      primary treatment for selected patients with suspected uncomplicated
      appendicitis, this is unlikely to supersede appendectomy at present. Selection
      bias and crossover to surgery in the RCTs suggest that appendectomy is still the
      gold standard therapy for acute appendicitis.

PMID- 20041250
TI  - Therapeutic efficacy comparison of two surgical procedures to treat middle
      thoracic esophageal carcinoma.
AB  - BACKGROUND: The aim of this study was to evaluate the therapeutic efficacy of two
      surgical procedures used to treat middle thoracic esophageal squamous cell
      carcinoma and compare the results. METHODS: A total of 167 patients with middle
      thoracic esophageal squamous cell carcinoma were included in the study, including
      102 patients who underwent Ivor-Lewis esophagectomy and another 65 who underwent
      dual-incision esophagectomy through the left chest and neck (Dual-incision). The
      Kaplan-Meier method was used to calculate the survival rate, and Cox regression
      analysis was performed to identify prognostic risk factors. RESULTS:
      Perioperative complications occurred in 35 patients (21%). The incidence rate of
      recurrent laryngeal nerve injury and anastomotic leakage was higher in the Dual
      incision group (p < 0.05), and the incidence rate of gastric retention was higher
      in the Ivor-Lewis group. However, there were no statistically significant
      differences. The 3-year local recurrence rate was 37.3% in the Ivor-Lewis group
      and 40% in the Dual-incision group (p > 0.05). The overall 5-year survival rate
      was 34.6%; the rates of the Ivor-Lewis group and the Dual-incision group were
      36.0 and 32.3%, respectively (p > 0.05). The Cox analysis indicated that the pTNM
      staging was an independent prognostic risk factor (p = 0.00, hazard ratio =
      2.69). CONCLUSIONS: Both Ivor-Lewis esophagectomy and Dual-incision esophagectomy
      through the left chest and neck are options for treating middle thoracic
      esophageal squamous cell carcinoma. It is suggested that a patient's individual
      condition be taken into account when choosing the operative approach.

PMID- 20041251
TI  - Addressing the global burden of surgical disease: proceedings from the 2nd annual
      symposium at the American College of Surgeons.
AB  - In the past decade, interest in surgery as a means to improve public health and
      engage in international service has increased significantly. International
      organizations, academic institutions, professional associations, and humanitarian
      aid organizations recognize that disparate access to surgical care affects global
      health and they have recently joined forces to address access to surgical care.
      Current initiatives focus on quantitatively defining surgical disparity,
      prioritizing a surgical agenda, and developing economically sustainable models
      for health care assistance, training, and delivery. The Global Burden of Surgical
      Disease Working Group (GBoSD WG) strives to (1) quantitatively define global
      disparity in surgical care; (2) assess unmet surgical need; (3) identify
      priorities; (4) develop sustainable models for improved health care delivery; and
      (5) advocate for a surgical presence within the global public health agenda. This
      article formally introduces the GBoSD Working Group and papers presented during
      the 2009 Symposium at the American College of Surgeons in Chicago.

PMID- 20041252
TI  - Introducing the plant RNA editing prediction and analysis computer tool PREPACT
      and an update on RNA editing site nomenclature.
AB  - Transcripts in mitochondria and chloroplasts of land plants are modified through
      RNA editing, the exchanges of pyrimidines-a post-transcriptional process that may
      affect more than 1,000 sites in the mitochondrial transcriptomes of some plant
      species. RNA editing mainly acts as a correcting mechanism to re-create
      evolutionary conserved coding sequences on mRNA level and can be reasonably well
      predicted in new plant organelle gene sequence data. Identification and
      annotation of RNA editing sites is cumbersome and error-prone for larger data
      sets or organelle sequences subject to highly frequent RNA editing. We here
      present PREPACT, WWW-accessible at http://www.prepact.de , which allows
      prediction, analysis, annotation and graphical display of RNA editing sites for
      both directions of pyrimidine exchanges, using the recently proposed RNA editing
      nomenclature. PREPACT offers prediction of RNA editing, analysis of partial
      editing in cDNA pools and a BLASTX mode for simultaneous prediction of genes and
      RNA editing sites in novel sequences. Output options include (i) lists and
      annotations of RNA editing sites, (ii) sequence alignments with user-controlled
      color highlighting of editings, (iii) graphical displays of RNA editing in
      sequences and alignments. Finally, binary matrices of editing positions can be
      produced that may be used for downstream (e.g. phylogenetic) analyses.

PMID- 20041253
TI  - Suppression of GhAGP4 gene expression repressed the initiation and elongation of
      cotton fiber.
AB  - Cotton fibers, important natural raw materials for the textile industry, are
      trichomes elongated from epidermal cells of cotton ovules. To date, a number of
      genes have been shown to be critical for fiber development. In this study, the
      roles of genes encoding fasciclin-like arabinoglactan proteins (FLAs) in cotton
      fiber were examined by transforming RNA interfering (RNAi) construct. The RNAi
      according to the sequence of GhAGP4 caused a significant reduction of its mRNA
      level, and the expression of other three FLAs (GhAGP2, GhAGP3, GhFLA1) were also
      partially suppressed. The fiber initiation and fiber elongation were inhibited in
      the transgenic plants. As for the mature fibers of transgenic cotton, the fiber
      length became significantly shorter and the fiber quality became worse. In
      addition, the RNAi of GhAGP4 also affected the cytoskeleton network and the
      cellulose deposition of fiber cells. Through ovule culture, it was found that the
      expression of cotton FLA genes were upregulated by GA(3), especially for GhAGP2
      and GhAGP4. These results indicate that the FLAs are essential for the initiation
      and elongation of cotton fiber development.

PMID- 20041254
TI  - Selection system and co-cultivation medium are important determinants of
      Agrobacterium-mediated transformation of sugarcane.
AB  - A reproducible method for transformation of sugarcane using various strains of
      Agrobacterium tumefaciens (A. tumefaciens) (AGL0, AGL1, EHA105 and LBA4404) has
      been developed. The selection system and co-cultivation medium were the most
      important factors determining the success of transformation and transgenic plant
      regeneration. Plant regeneration at a frequency of 0.8-4.8% occurred only when
      callus was transformed with A. tumefaciens carrying a newly constructed
      superbinary plasmid containing neomycin phosphotransferase (nptII) and beta
      glucuronidase (gusA) genes, both driven by the maize ubiquitin (ubi-1) promoter.
      Regeneration was successful in plants carrying the nptII gene but not the
      hygromycin phosphotransferase (hph) gene. NptII gene selection was imposed at a
      concentration of 150 mg/l paromomycin sulphate and applied either immediately or
      4 days after the co-cultivation period. Co-cultivation on Murashige and Skoog
      (MS)-based medium for a period of 4 days produced the highest number of
      transgenic plants. Over 200 independent transgenic lines were created using this
      protocol. Regenerated plants appeared phenotypically normal and contained both
      gusA and nptII genes. Southern blot analysis revealed 1-3 transgene insertion
      events that were randomly integrated in the majority of the plants produced.

PMID- 20041255
TI  - Platelet activating factor stimulates arachidonic acid release in differentiated
      keratinocytes via arachidonyl non-selective phospholipase A2.
AB  - Platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)
      is known to be present in excess in psoriatic skin, but its exact role is
      uncertain. In the present study we demonstrate for the first time the role of
      group VI PLA(2) in PAF-induced arachidonic acid release in highly differentiated
      human keratinocytes. The group IValpha PLA(2) also participates in the release,
      while secretory PLA(2)s play a minor role. Two anti-inflammatory synthetic fatty
      acids, tetradecylthioacetic acid and tetradecylselenoacetic acid, are shown to
      interfere with signalling events upstream of group IValpha PLA(2) activation. In
      summary, our major novel finding is the involvement of the arachidonyl non
      selective group VI PLA(2) in PAF-induced inflammatory responses.

PMID- 20041256
TI  - Vascular endothelial growth factor +405 C/G polymorphism is highly associated
      with an increased risk of endometriosis in Turkish women.
AB  - OBJECTIVE: Endometriosis is a chronic gynecological disease characterized by the
      growth of hormonally responsive, endometrial tissue outside the uterine cavity.
      The present study aims to analyze two vascular endothelial growth factor (VEGF)
      polymorphisms (-460 C/T and +405 C/G) in Turkish women with and without
      endometriosis. STUDY DESIGN: A case-control study was undertaken at the
      Infertility Department of Zekai Tahir Burak Women's Health Care Education and
      Research Hospital. The single nucleotide polymorphisms, -460 C/T and +405 C/G, in
      the 5'-untranslated region of the VEGF gene were tested in 98 affected women and
      94 women with no laparoscopic evidence of disease. Endometriosis was also
      confirmed histologically. Following genomic extraction of genomic DNA, genotyping
      of the -460 C/T and +405 C/G polymorphisms of the VEGF gene were performed by
      polymerase chain reaction and restriction fragment length polymorphism assay.
      Nominal data were evaluated by Pearson Chi-square or Fisher's Exact test, where
      applicable. Odds ratios and 95% confidence intervals were also calculated. A P
      value less than 0.05 was considered statistically significant. RESULTS:
      Demographic data were similar among groups. The genotype and allele frequencies
      of the -460 C/T polymorphism did not differ significantly between cases and
      controls. In contrast, the genotype (P < 0.001) and allele frequencies (P <
      0.001) of +405 C/G polymorphism showed a significant difference between cases and
      controls. Regardless of the early or advanced stage, women with endometriosis
      showed a higher incidence of the +405 GC genotype and +405G allele when compared
      with the controls. CONCLUSIONS: These data suggest that VEGF +405 GC genotype and
      +405G allele may be associated with the risk of developing early and advanced
      stage endometriosis in the Turkish population.

PMID- 20041257
TI  - Reproductive outcome following hysteroscopic septal resection in patients with
      infertility and recurrent abortions.
AB  - OBJECTIVES: To evaluate the outcome of hysteroscopic septal resection in patients
      with infertility and recurrent abortions. MATERIALS AND METHODS: This was a
      retrospective clinical analysis of 170 patients who underwent hysteroscopic
      septal resection by monopolar electrode (Collin's) knife. A second-look office
      hysteroscopy was performed in all cases within 2 months. The mean follow-up
      period was 28.5 months. RESULTS: The mean age of the patients was 25.6 years. The
      presenting clinical complaint was recurrent abortions in 68.2% patients,
      infertility in 17.6% patients and preterm deliveries in 14.1% patients. Final
      reproductive outcome was assessed for 152 patients, after excluding patients with
      other confounding factors, interfering in pregnancy outcome. There was a
      significant difference in reduction of number of miscarriages (91.5% pre-surgery;
      12.9% post-surgery: p = 0.02) and increase in term deliveries (2.5% pre-surgery;
      79.5% post-surgery: p = 0.01), while the number of preterm deliveries remained
      almost the same (6.1% pre-surgery; 7.5% post-surgery). Thirteen out of 23
      infertile patients (56.5%) conceived after septal resection. The take home baby
      rate was increased from 8.5 to 87.1%. Cumulative first live birth rate revealed
      that 51.2% women had their first live birth within 10-15 months. There was an
      increased incidence (43.2%) of cesarean section in mode of delivery. In 11/170
      patients, repeat hysteroscopy suggested the presence of uterine adhesions which
      needed hysteroscopic adhesiolysis and three patients required repeat septal
      resection. CONCLUSIONS: Hysteroscopic septal resection for women with history of
      recurrent abortions, preterm deliveries and in women with infertility is a safe
      and effective method of choice for improving the obstetric outcome.

PMID- 20041258
TI  - Ultrasound-guided localisation of trachea for surgical tracheostomy.

PMID- 20041260
TI  - Contact allergy to thiurams: multifactorial analysis of clinical surveillance
      data collected by the IVDK network.
AB  - PURPOSE: To analyse the association between occupation (represented by job title)
      and contact allergy to thiuram vulcanising agents based on data of a clinical
      registry (IVDK, www.ivdk.org ). METHODS: Clinical, demographic and allergy patch
      test data of all patients tested between 1992 and 2006 with the thiuram mix (1%
      in petrolatum) as part of the baseline series was analysed (n = 121,051). Poisson
      regression analysis was used to quantify the association between different
      occupations (and other relevant factors) and a positive patch test reaction to
      the thiuram mix. Furthermore, the time trend of sensitisation prevalence was
      analysed in high-risk occupational subgroups identified. RESULTS: In comparison
      to a largely unexposed reference group (office workers and teachers), rubber
      manufacturers had a significantly elevated risk (prevalence ratio (PR): 5.1, 95%
      confidence interval (CI) 2.0-10.5). However, health care workers such as
      physicians and dentists (PR: 3.8, 95% CI: 3.0-4.8) or nursing staff (PR: 3.0, 95%
      CI: 2.5-3.6) as well as meat and fish processors (PR 3.5, 95% CI: 2.2-5.3) and
      cleaners (PR 3.1, 95% CI: 2.5-3.8) were found to have a high sensitisation risk
      as well. In case of health care workers, a significant downward trend during the
      study period was observed; while in food processors and cleaners, sensitisation
      prevalence remained largely stable. CONCLUSION: The adjusted multifactorial
      analysis identified occupations yet unknown to be associated with elevated
      thiuram contact allergy risk, e.g., food processors and cleaners. Thus, (i)
      further in-depth research can be targeted and (ii) efforts to prevent
      sensitisation to thiurams focussed, e.g., by limiting thiuram concentrations in
      products to a residual level which is technically inevitable.

PMID- 20041259
TI  - Olfactory and gustatory function in irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is the most common, functional disorder diagnosed
      by gastroenterologists. It is still unclear whether IBS has a central etiology,
      e.g., hyperreactivity of the brain, or a peripheral etiology, e.g., stimulation
      of olfactory/gustatory receptors on enterochromaffin cells, followed by serotonin
      release and changed gut motility. Testing the odor identification (ID), odor
      discrimination (DIS) and odor threshold (THR) as well as the total taste and the
      taste qualities "sweet", "sour", "salty" and "bitter" should be of help for
      determining the etiology. To our knowledge, this is the first study investigating
      the olfactory/gustatory function in IBS patients. The olfactory/gustatory
      function of 43 patients (32 women, 11 men) suffering from IBS as defined by the
      ROME III criteria was investigated by means of validated tests (Sniffin' Sticks
      and taste strips). Compared to normative data, scores of THR were decreased and
      scores of ID and DIS were increased in IBS patients. Additionally, when compared
      to normative data, there was no difference in the taste function of IBS patients.
      Assuming that THR reflects more the peripheral olfactory function, whereas ID and
      DIS are influenced by central activity, and that taste did not differ in IBS
      patients compared to normative data, this supports the idea of a central etiology
      of IBS.

PMID- 20041261
TI  - A population level computational model of the basal ganglia that generates
      parkinsonian Local Field Potential activity.
AB  - Recordings from the basal ganglia's subthalamic nucleus are acquired via
      microelectrodes immediately prior to the application of Deep Brain Stimulation
      (DBS) treatment for Parkinson's Disease (PD) to assist in the selection of the
      final point for the implantation of the DBS electrode. The acquired recordings
      reveal a persistent characteristic beta band peak in the power spectral density
      function of the Local Field Potential (LFP) signals. This peak is considered to
      lie at the core of the causality-effect relationships of the parkinsonian
      pathophysiology. Based on LFPs acquired from human subjects during DBS for PD, we
      constructed a computational model of the basal ganglia on the population level
      that generates LFPs to identify the critical pathophysiological alterations that
      lead to the expression of the beta band peak. To this end, we used experimental
      data reporting that the strengths of the synaptic connections are modified under
      dopamine depletion. The hypothesis that the altered dopaminergic modulation may
      affect both the amplitude and the time course of the postsynaptic potentials is
      validated by the model. The results suggest a pivotal role of both of these
      parameters to the pathophysiology of PD.

PMID- 20041262
TI  - Independence of the unimodal tuning of firing rate from theta phase precession in
      hippocampal place cells.
AB  - There are two prominent features for place cells in rat hippocampus. The firing
      rate remarkably increases when rat enters the cell's place field and reaches a
      maximum around the center of place field, and it decreases when the animal
      approaches the end of the place field. Simultaneously the spikes gradually and
      monotonically advance to earlier phase relative to hippocampal theta rhythm as
      the rat traverses along the cell's place field, known as temporal coding. In this
      paper, we investigate whether two main characteristics of place cell firing are
      independent or not by mainly focusing on the generation mechanism of the unimodal
      tuning of firing rate by using a reduced CA1 two-compartment neuron model. Based
      on recent evidences, we hypothesize that the coupling of dendritic with the
      somatic compartment is not constant but dynamically regulated as the animal moves
      further along the place field, in contrast to previous two-compartment modeling.
      Simulations show that the regulable coupling is critically responsible for the
      generation of unimodal firing rate profile in place cells, independent of phase
      precession. Predictions of our model accord well with recent observations like
      occurrence of phase precession with very low as well as high firing rate (Huxter
      et al. Nature 425:828-832, 2003) and persistency of phase precession after
      transient silence of hippocampus activity (Zugaro et al. Nat Neurosci 8:67-71,
      2005.

PMID- 20041263
TI  - In vitro hepatic maturation of human embryonic stem cells by using a mesenchymal
      cell line derived from murine fetal livers.
AB  - Hepatocytes derived from human embryonic stem cells (hESCs) are an attractive
      cell source for regenerative medicine. We previously reported the differentiation
      of hESCs into alpha-fetoprotein (AFP)-producing endodermal cells by using
      extracellular matrix and growth factors. We also reported the establishment of
      the MLSgt20 cell line, which was derived from mesenchymal cells residing in
      murine fetal livers and accelerated the hepatic maturation of both murine hepatic
      progenitor cells and murine ESCs. In this study, hESC-derived AFP-producing cells
      were isolated by using a flow cytometer and co-cultured with MLSgt20 cells. The
      co-cultured hESC-derived AFP-producing cells had the immunocytological
      characteristics of hepatocytes, expressed mature hepatocyte markers (as indicated
      by reverse transcription and the polymerase chain reaction), and displayed higher
      hepatocyte functions including ammonia removal, cytochrome P450 3A4/7 activity,
      and the ability to produce and store glycogen. However, the MLSgt20 cells did not
      directly cause undifferentiated hESCs to mature into hepatocyte-like cells. The
      co-culture method was thus successfully shown to induce the differentiation of
      hESC-derived endodermal cells into functional hepatocyte-like cells.

PMID- 20041264
TI  - Surgeon's volume and number of lymph nodes in assessing colorectal cancer surgery
      and multimodal treatment quality.

PMID- 20041265
TI  - Endoscopic submucosal dissection: can it safely expand indications for a
      minimally invasive approach to patients with early gastric cancer?

PMID- 20041266
TI  - Findings at endoscopic retrograde cholangiopancreatography after endoscopic
      treatment of postcholecystectomy bile leaks.
AB  - BACKGROUND: Although the endoscopic management of bile leaks after
      cholecystectomy (CCY) is well established, the yield of a routine endoscopic
      retrograde cholangiogram (ERC) with a bile duct sweep at the time of stent
      removal is unclear. This study aimed to describe the prevalence of abnormal
      findings at follow-up ERC to determine whether upper endoscopy with stent removal
      and without cholangiography would suffice. METHODS: A retrospective cohort
      analysis of all patients referred for initial and follow-up ERC with post-CCY
      bile leak was performed. The rate of abnormal findings was measured including
      choledocholithiasis, biliary strictures, and persistent bile leaks at follow-up
      ERC. Secondarily, the study sought to define the clinical characteristics of
      patients who demonstrated stones or sludge at follow-up assessment. RESULTS:
      Between January, 2003 and April, 2008, 105 patients underwent initial and follow
      up ERC. After a mean interval of 6.9 +/- 2.7 weeks between endoscopies, 29
      (27.6%) of the 105 patients demonstrated one or more abnormalities including
      persistent bile leak (n = 8), common bile duct (CBD) stones (n = 12), and CBD
      sludge alone (n = 9). In the subgroup analysis of the patients who underwent a
      balloon sweep at initial and follow-up ERC, the prevalence of CBD stones or
      sludge at the follow-up ERC was 17.6%. Besides stones during the initial ERC, no
      significant clinical predictors of CBD stones were found at follow-up ERC
      including surgical approach, interval between endoscopies, and location of bile
      leak. CONCLUSION: After endoscopic treatment of a bile leak, the prevalence of
      abnormalities at follow-up ERC is significant. A repeat cholangiogram with a
      balloon sweep is preferred at the time of stent removal.

PMID- 20041267
TI  - Adiponectin but not leptin is involved in early hepatic disease in morbidly obese
      patients.
AB  - BACKGROUND: Pathologic changes in the liver are common in morbidly obese
      patients, and insulin resistance may potentiate the progression of nonalcoholic
      steatohepatitis to fibrosis and cirrhosis. This study investigates the impact of
      leptin and adiponectin in morbidly obese diabetic and nondiabetic patients with
      regard to histopathologic changes in the liver. METHODS: Thirty-seven morbidly
      obese patients who underwent bariatric surgery with liver biopsies were enrolled
      in the study. Fourteen were diabetic and 23 were nondiabetic. Intraoperative
      liver tissue was sent for histopathologic analysis and extraneous intraoperative
      tissue was snap-frozen in liquid nitrogen. Total RNA was extracted and RNA was
      reverse transcribed to cDNA. Real-time quantitative PCR was performed to
      determine relative gene expression levels. The data were analyzed using a
      logarithmic transformation and normalized by 18S ribosome expression. Student's t
      test was used for statistical analysis with p < or = 0.05 as significant.
      RESULTS: Adiponectin expression was downregulated 4.4-fold (p < or = 0.05) in
      liver samples with evidence of inflammation on pathology. When hepatic
      inflammation was evaluated separately, there were no statistically significant
      differences in adiponectin levels between the diabetic and nondiabetic patients.
      However, overall adiponectin levels in hepatic samples of diabetic patients were
      3.8-fold higher than those of nondiabetic patients (p < or = 0.05). There were no
      significant differences in leptin levels regardless of hepatic pathology or
      diabetic status. CONCLUSIONS: This study illustrates that there is a
      downregulation of adiponectin in morbidly obese patients with inflammatory
      infiltrates in the liver. Variations in adiponectin levels could be an indicator
      of disease progression since inflammatory infiltrates are commonly associated
      with nonalcoholic steatohepatitis (NASH) in morbidly obese patients. Currently,
      we are using human myofibroblasts derived from livers of morbidly obese people to
      further investigate the molecular mechanisms involved in the progression of fatty
      liver to fibrosis and cirrhosis.

PMID- 20041268
TI  - Increased mRNA expression of epidermal growth factor receptor, human epidermal
      receptor, and survivin in human gastric cancer after the surgical stress of
      laparotomy versus carbon dioxide pneumoperitoneum in a murine model.
AB  - BACKGROUND: Surgical impact may be associated with enhanced tumor growth and
      chemoresistance. This study aimed to evaluate the effect of surgical impact on
      the mRNA expression of survivin, epidermal growth factor receptor (EGFR), and
      human epidermal receptor (HER2) in tumors after pneumoperitoneum versus
      laparotomy. METHODS: Nude mice were inoculated intraperitoneally with human
      gastric cancer cells (MKN45). Then laparotomy, carbon dioxide (CO(2))
      pneumoperitoneum, and anesthesia alone were performed randomly, after which EGFR,
      HER2, and survivin mRNA expression using reverse transcription-polymerase chain
      reaction (RT-PCR) was evaluated. RESULTS: The expression of EGFR and HER2 mRNA
      increased significantly after the experiment. However, it was higher after
      laparotomy than after CO(2) pneumoperitoneum at almost all examined time points.
      Survivin mRNA expression increased significantly in the first 48 h, then returned
      to the control level. It was higher after laparotomy than after CO(2)
      pneumoperitoneum 48 h after the surgical procedures. CONCLUSION: The expression
      of EGFR, HER2, and survivin increased after each surgical procedure. However it
      was lower after CO(2) pneumoperitoneum than after laparotomy. This might be
      associated with changes in the chemosensitivity of the remnant cancer cells after
      surgery, supporting the use of minimally invasive surgery for cancer.

PMID- 20041269
TI  - Genetic interaction between AINTEGUMENTA (ANT) and the ovule identity genes
      SEEDSTICK (STK), SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2).
AB  - AINTEGUMENTA (ANT) promotes initiation and growth of ovule integuments which cell
      fate is specified by ovule identity factors, such as SEEDSTICK (STK),
      SHATTERPROOF1 (SHP1) and SHATTERPROOF2 (SHP2). To study the genetic interaction
      between ANT and the ovule identity genes, we have obtained a stk shp1 shp2 ant
      quadruple mutant. The molecular and morphological characterization of the
      quadruple mutant and its comparison with the stk shp1 shp2 triple mutant, the
      shp1 shp2 ant triple mutant and the stk ant double mutant are here presented.

PMID- 20041270
TI  - Efficacy and safety of VEPTR instrumentation for progressive spine deformities in
      young children without rib fusions.
AB  - This retrospective study analyses 23 children treated with vertical expandable
      prosthetic titanium rib (VEPTR) for correction of non-congenital early onset
      spine deformities. After the index procedure (IP), the device was lengthened at 6
      month intervals. The average (av) age at the time of IP was 6.5 years (1.11
      10.5). The av follow-up time was 3.6 years (2-5.8). Diagnosis included 1 early
      onset idiopathic scoliosis, 11 neuromuscular, 2 post-thoracotomy scoliosis, 1
      Sprengel deformity, 2 hyperkyphosis, 1 myopathy and 5 syndromic. Surgeries (187)
      included 23 IPs, av 6.5 (4-10) device expansions per patient (149) and 15
      unplanned surgeries. 23 complications (0.13 per surgery) included 10 skin
      sloughs, 5 implant dislocations, 2 rod breakages and 6 infections. Coronal Cobb
      angle was av 68 degrees (11 degrees -111 degrees ), at follow-up av 54 degrees (0
      degrees -105 degrees). Pelvic obliquity was av 33 degrees (13 degrees -60 degrees
      ), at follow-up av 16 degrees (0 degrees -42 degrees ). T1 tilt was av 29 degrees
      (5 degrees -84 degrees ), two remained unchanged, the remainder improved 10
      degrees -68 degrees. Sagittal plane: All but two had stable profiles, two
      hyperkyphosis of 110 degrees /124 degrees improved to 56 degrees /86 degrees.
      Space available for lung ratio was less than 90% in ten before the IP, improved
      in nine and deteriorated in one. Originally designed for thoracic insufficiency
      syndromes related to rib and vertebral anomalies, VEPTR proved to be a valuable
      alternative to dual growing rods for non-congenital early onset spine
      deformities. The complication rate was lower, the control of the sagittal plane
      and the pelvic obliquity was as good, but the correction of the coronal plane
      deformity was less than growing rods. However, VEPTR's spine-sparing approach
      might provoke less spontaneous spinal fusion and ease the final correction at
      maturity.

PMID- 20041271
TI  - The efficacy of rhBMP-2 versus autograft for posterolateral lumbar spine fusion
      in elderly patients.
AB  - Few studies have specifically examined the outcomes following rhBMP-2 usage in
      patients 65 years and older. The purpose of this retrospective study is to
      evaluate the efficacy of rhBMP-2 with allograft versus autograft for
      posterolateral lumbar fusion in patients 65 years and older. One hundred twenty
      seven patients were divided into three groups based on fusion material and age.
      Subjects in group A (n = 34) consisted of patients 65 years and older who
      received rhBMP-2 and allograft. Group B (n = 52) was composed of patients under
      65 years of age with rhBMP-2 and allograft. Subjects in group C (n = 41) were 65
      years and older with autograft use. A comparison was made of fusion rate, fusion
      time (noticed, solid), clinical outcome, VAS, perioperative complications and
      revision rate between each group. The fusion rate and fusion time were similar in
      groups A and C; however, these were lower than that observed in group B. Clinical
      outcomes were similar amongst the groups. There were no significant differences
      in VAS and perioperative complication rate between groups A and C. In patients 65
      years and older, rhBMP-2 with allograft may lead to acceptable fusion rates and
      fusion times, good clinical outcomes and reduced perioperative complications. The
      combination of rhBMP-2 with allograft yields equivalent outcomes as autograft in
      elderly patients undergoing instrumented posterolateral lumbar fusion.
      Additionally, when compared to patients under 65 years of age undergoing
      posterolateral lumbar fusion, the use of rhBMP-2 was not sufficient to overcome
      all aspects of the age-related weakened osteoinductive capacity encountered in
      elderly patients.

PMID- 20041272
TI  - Can uranium follow the iron-acquisition pathway? Interaction of uranyl-loaded
      transferrin with receptor 1.
AB  - Transferrin receptor 1 (R(D)) binds iron-loaded transferrin and allows its
      internalization in the cytoplasm. Human serum transferrin also forms complexes
      with metals other than iron, including uranium in the uranyl form (UO(2)(2+)).
      Can the uranyl-saturated transferrin (TUr(2)) follow the receptor-mediated iron
      acquisition pathway? In cell-free assays, TUr(2) interacts with R(D) in two
      different steps. The first is fast, direct rate constant, k(1) = (5.2 +/- 0.8) x
      10(6) M(-1) s(-1); reverse rate constant, k(-1) = 95 +/- 5 s(-1); and
      dissociation constant K(1) = 18 +/- 6 microM. The second occurs in the 100-s
      range and leads to an increase in the stability of the protein-protein adduct,
      with an average overall dissociation constant K(d) = 6 +/- 2 microM. This kinetic
      analysis implies in the proposed in vitro model possible but weak competition
      between TUr(2) and the C-lobe of iron-loaded transferrin toward the interaction
      with R(D).

PMID- 20041273
TI  - Improving performance of docking-based virtual screening by structural
      filtration.
AB  - In the current study an innovative method of structural filtration of docked
      ligand poses is introduced and applied to improve the virtual screening results.
      The structural filter is defined by a protein-specific set of interactions that
      are a) structurally conserved in available structures of a particular protein
      with its bound ligands, and b) that can be viewed as playing the crucial role in
      protein-ligand binding. The concept was evaluated on a set of 10 diverse
      proteins, for which the corresponding structural filters were developed and
      applied to the results of virtual screening obtained with the Lead Finder
      software. The application of structural filtration resulted in a considerable
      improvement of the enrichment factor ranging from several folds to hundreds folds
      depending on the protein target. It appeared that the structural filtration had
      effectively repaired the deficiencies of the scoring functions that used to
      overestimate decoy binding, resulting into a considerably lower false positive
      rate. In addition, the structural filters were also effective in dealing with
      some deficiencies of the protein structure models that would lead to false
      negative predictions otherwise. The ability of structural filtration to recover
      relatively small but specifically bound molecules creates promises for the
      application of this technology in the fragment-based drug discovery.

PMID- 20041274
TI  - Incidence of cancer among female patients with systemic lupus erythematosus in
      Korea.
AB  - This study aims to ascertain the incidence of cancer in patients with systemic
      lupus erythematosus (SLE) in comparison with that in the general population in
      Korea, and to identify the cancer-types, the organ involvement, and the
      association with immunosuppressive therapy. The study subjects were consecutive
      SLE patients evaluated at Kangnam St. Mary's hospital between 1997 and 2007. The
      incidence rate of cancer was calculated and was analyzed in comparison to that of
      age- and sex-matched cohort obtained from the Korea National Cancer Registry.
      Nine hundred fourteen patients were observed for a total of 5,716 person-years. A
      total of 16 cases of cancer occurred. The average age at the diagnosis of cancer
      and the mean disease duration were 43 years and 11 years, respectively. The
      standardized incidence ratio (SIR) of all cancers was 1.45 (95% CI 0.74-2.16);
      The SIRs for the three most frequent cancers were 3.42 for cervix cancer (CI 0.00
      7.26), 15.37 for non-Hodgkin's lymphoma (NHL; CI 2.90-37.68), and 43.55 for
      bladder cancer (CI 8.21-106.78). There were significant differences in the
      hematologic and renal involvement between SLE patients with cancer and without.
      Cyclophosphamide therapy, especially with cumulative dose more than 6 g (p =
      0.017), seemed to contribute to the increased risk of cancer. Long disease
      duration, damage, and hematologic involvement were associated with increased risk
      of cancer occurrence. SLE patients are at high risk for NHL and bladder cancer.
      Active cancer screening is required in SLE patients with long disease duration
      and damage who are treated with high dose cyclophosphamide.

PMID- 20041275
TI  - Isoform specific phosphorylation of p53 by protein kinase CK1.
AB  - The ability of three isoforms of protein kinase CK1 (alpha, gamma(1), and delta)
      to phosphorylate the N-terminal region of p53 has been assessed using either
      recombinant p53 or a synthetic peptide reproducing its 1-28 sequence. Both
      substrates are readily phosphoylated by CK1delta and CK1alpha, but not by the
      gamma isoform. Affinity of full size p53 for CK1 is 3 orders of magnitude higher
      than that of its N-terminal peptide (K (m) 0.82 muM vs 1.51 mM). The preferred
      target is S20, whose phosphorylation critically relies on E17, while S6 is
      unaffected despite displaying the same consensus (E-x-x-S). Our data support the
      concept that non-primed phosphorylation of p53 by CK1 is an isoform-specific
      reaction preferentially affecting S20 by a mechanism which is grounded both on a
      local consensus and on a remote docking site mapped to the K(221)RQK(224) loop
      according to modeling and mutational analysis.

PMID- 20041276
TI  - The exploration of meditation in the neuroscience of attention and consciousness.
AB  - Many recent behavioral and neuroscientific studies have revealed the importance
      of investigating meditation states and traits to achieve an increased
      understanding of cognitive and affective neuroplasticity, attention and self
      awareness, as well as for their increasingly recognized clinical relevance. The
      investigation of states and traits related to meditation has especially
      pronounced implications for the neuroscience of attention, consciousness, self
      awareness, empathy and theory of mind. In this article we present the main
      features of meditation-based mental training and characterize the current
      scientific approach to meditation states and traits with special reference to
      attention and consciousness, in light of the articles contributed to this issue.

PMID- 20041277
TI  - Cover essay: The fearsome and the fuzzy.

PMID- 20041278
TI  - Correlation of retinal sensitivity with visual acuity and macular thickness in
      eyes with idiopathic epimacular membrane.
AB  - The aim of this study was to analyze macular function by measuring the
      sensitivity of the macula with fundus-related microperimetry and to compare the
      results with the best corrected visual acuity (BCVA) and foveal retinal thickness
      measured by optical coherence tomography (OCT) in patients with idiopathic
      epimacular membrane. We prospectively reviewed 66 eyes with idiopathic epimacular
      membrane and 35 normal healthy eyes in patients who had undergone fundus-related
      microperimetry and OCT. The macular sensitivity was measured using the recently
      introduced fundus-related microperimeter, MP-1. The mean retinal sensitivities in
      the central 10 degrees (central microperimetry, cMP-1) and in the paracentral 10
      20 degrees (paracentral microperimetry, pMP-1) areas were determined and
      correlated with the BCVA and OCT-measured foveal thickness. Eyes with epimacular
      membranes showed significantly lower log MAR BCVA (P < 0.001) and cMP-1
      microperimetry sensitivity (P < 0.001) and significantly higher OCT foveal
      thickness (P < 0.001) than control eyes. There was a significant correlation
      between the BCVA and mean retinal sensitivity in the cMP-1 (r (2) = 0.26, P <
      0.001) and the pMP-1 (r (2) = 0.07, P = 0.008) areas. A significant negative
      correlation was observed between the foveal thickness and the mean retinal
      sensitivity in the cMP-1 (r (2) = 0.13, P < 0.001) area. Retinal sensitivity in
      the central macular area determined by MP-1 microperimetry was significantly
      correlated with BCVA and with foveal thickness. The combination of OCT and
      microperimetry may help a better evaluation of the patients with idiopathic
      epimacular membrane.

PMID- 20041279
TI  - Prediction of Xaa-Pro peptide bond conformation from sequence and chemical
      shifts.
AB  - We present a program, named Promega, to predict the Xaa-Pro peptide bond
      conformation on the basis of backbone chemical shifts and the amino acid
      sequence. Using a chemical shift database of proteins of known structure together
      with the PDB-extracted amino acid preference of cis Xaa-Pro peptide bonds, a
      cis/trans probability score is calculated from the backbone and (13)C(beta)
      chemical shifts of the proline and its neighboring residues. For an arbitrary
      number of input chemical shifts, which may include Pro-(13)C(gamma), Promega
      calculates the statistical probability that a Xaa-Pro peptide bond is cis.
      Besides its potential as a validation tool, Promega is particularly useful for
      studies of larger proteins where Pro-(13)C(gamma) assignments can be challenging,
      and for on-going efforts to determine protein structures exclusively on the basis
      of backbone and (13)C(beta) chemical shifts.

PMID- 20041280
TI  - Fluorescent molecular rotors as dyes to characterize polysorbate-containing IgG
      formulations.
AB  - PURPOSE: The aim was to evaluate fluorescent molecular rotors (DCVJ and CCVJ),
      which are mainly sensitive to viscosity, for the characterization of polysorbate
      containing IgG formulations and compare them to the polarity-sensitive dyes ANS,
      Bis-ANS and Nile Red. METHODS: IgG formulations with polysorbate 20 or 80 were
      stressed below the aggregation temperature and analyzed by steady-state and time
      resolved fluorescence and by HP-SEC with UV and fluorescent dye detection (Bis
      ANS and CCVJ). Furthermore, commercial protein preparations of therapeutic
      proteins (Enbrel 50 mg, Humira 40 mg and MabThera 100 mg) were aggregated
      accordingly and analyzed with CCVJ fluorescence and HP-SEC. RESULTS: Contrarily
      to (Bis-)ANS and Nile Red, the molecular rotors DCVJ and CCVJ showed low
      background fluorescence in polysorbate-containing buffers. Time-resolved
      fluorescence experiments confirmed the steady-state fluorescence data. Both DCVJ
      and CCVJ showed enhanced fluorescence intensity for aggregated IgG formulations
      and were suitable for the characterization of polysorbate-containing IgG
      formulations in steady-state fluorescence and HP-SEC with dye detection (CCVJ).
      CCVJ was capable of detecting thermally induced aggregation in the commercial
      polysorbate-containing products Enbrel 50 mg, Humira 40 mg and MabThera 100 mg.
      CONCLUSION: Fluorescent molecular rotors are suitable probes to detect
      aggregation in polysorbate-containing IgG formulations.

PMID- 20041281
TI  - Challenges in covering health disparities in local news media: an exploratory
      analysis assessing views of journalists.
AB  - News coverage of health topics influences knowledge, attitudes, and behaviors at
      the individual level, and agendas and actions at the institutional and policy
      levels. Because disparities in health often are the result of social inequalities
      that require community-level or policy-level solutions, news stories employing a
      health disparities news frame may contribute to agenda-setting among opinion
      leaders and policymakers and lead to policy efforts aimed at reducing health
      disparities. This study objective was to conduct an exploratory analysis to
      qualitatively describe barriers that health journalists face when covering health
      disparities in local media. Between June and October 2007, 18 journalists from
      television, print, and radio in Boston, Lawrence, and Worcester, Massachusetts,
      were recruited using a purposive sampling technique. In-depth, semi-structured
      interviews were conducted by telephone, and the crystallization/immersion method
      was used to conduct a qualitative analysis of interview transcripts. Our results
      revealed that journalists said that they consider several angles when developing
      health stories, including public impact and personal behavior change. Challenges
      to employing a health disparities frame included inability to translate how
      research findings may impact different socioeconomic groups, and difficulty
      understanding how findings may translate across racial/ethnic groups. Several
      journalists reported that disparities-focused stories are "less palatable" for
      some audiences. This exploratory study offers insights into the challenges that
      local news media face in using health disparities news frames in their routine
      coverage of health news. Public health practitioners may use these findings to
      inform communication efforts with local media in order to advance the public
      dialogue about health disparities.

PMID- 20041282
TI  - Intensive phase non-compliance to anti tubercular treatment in patients with HIV
      TB coinfection: a hospital-based cross-sectional study.
AB  - We aimed to study the prevalence and determinants of non compliance to intensive
      phase anti tubercular treatment (ATT) in 111 HIV-TB coinfection patients,
      attending the APEX Referral Center for HIV/AIDS at Medical College, Kolkata with
      a specially-designed, semi-structured, pre-tested questionnaire. Compliance was
      defined as taking >=95% of the total scheduled doses of anti-TB medicines during
      the intensive phase. Data was collected on socio-demographic parameters, disease
      information, patient's knowledge and barriers to treatment. The prevalence of non
      compliance to ATT in HIV-TB coinfection patients was found to be 40.5% (95% C.I.
      = 30.5, 50.5). Multivariate logistic regression analysis showed that absence of
      proper counseling, lack of knowledge about correct route of TB transmission,
      visiting quacks during ATT and the urge to leave treatment once patient started
      feeling better were the significant determinants of non-compliance. "No
      Counseling" increased chances of non- compliance (adjusted O.R.) 47.12 times (95%
      C.I. = 7.99, 195.27); thereby being the single most influential variable towards
      the outcome. The present study finds an alarmingly high prevalence of non
      compliance to ATT among HIV-TB coinfection patients. The results clearly indicate
      that adequate counseling about this coinfection and the importance of compliance,
      along with better patient-friendly orientation of DOTS programme is urgently
      needed. Collaborative TB-HIV activities are essential to ensure better ATT
      compliance in coinfection patients.

PMID- 20041283
TI  - Subliminal sexual stimuli facilitate genital response in women.
AB  - Visual sexual stimuli (VSS) are believed to undergo an automatic process of
      stimulus appraisal and (genital or subjective) response generation. Consistent
      with this belief, studies have found that subliminal VSS can facilitate responses
      to subsequent sexual stimulus presentations. We tested whether subliminal sexual
      stimuli facilitated a genital response in women and, furthermore, whether this
      genital response could be modulated by both opposite-sex stimuli and same-sex
      stimuli (i.e., whether the genital response to subliminal stimuli is category
      specific or nonspecific). Twenty heterosexual women underwent vaginal
      photoplethysmography while being subliminally (20 ms) exposed to same-sex,
      opposite-sex, and nonsexual slides in a priming experiment. Vaginal pulse
      amplitude was increased when target stimuli were preceded by both opposite-sex
      and same-sex priming stimuli relative to nonsexual priming stimuli. This finding
      suggests that subliminal VSS were subjected to automatic stimulus processing,
      thereby facilitating nonspecific genital response preparation. Results are
      discussed in terms of implicit and explicit memory access and the evolutionary
      benefit of female nonspecific genital response.

PMID- 20041284
TI  - Feederism in a woman.
AB  - Feederism is a fat fetish subculture in which individuals eroticize weight gain
      and feeding. Feeders are individuals who claim to become sexually aroused by
      feeding their partners and encouraging them to gain weight. Conversely, Feedees
      are individuals who claim to become sexually aroused by eating, being fed, and
      the idea or act of gaining weight. Very little is known about this population.
      This report describes a woman who self-identified as a Feedee. It is unclear, at
      present, whether female Feederism represents a unique paraphilia or a thematic
      variation of morphophilia or sexual masochism.

PMID- 20041285
TI  - SPA1 and DET1 act together to control photomorphogenesis throughout plant
      development.
AB  - The COP1/SPA complex and DET1 function to suppress photomorphogenesis in dark
      grown Arabidopsis seedlings. Additionally, they inhibit flowering under non
      inductive short-day conditions. The COP1/SPA complex and DET1, as part of the CDD
      complex, represent distinct high-molecular-weight complexes in Arabidopsis. Here,
      we provide genetic evidence that these complexes co-act in regulating plant
      development. We report the isolation of a spa1 enhancer mutation that represents
      a novel, very weak allele of det1. This det1 ( esp1 ) mutation caused no
      detectable mutant phenotype in the presence of wild-type SPA1, but showed
      strongly synergistic genetic interaction with the spa1 mutation in the control of
      seedling photomorphogenesis, anthocyanin accumulation, plant size as well as
      flowering time. On the biochemical level, the det1 ( esp1 ) spa1 double mutant
      showed higher HY5 protein levels than either single mutant or the wild type. The
      genetic interaction of spa1 and det1 mutations was further confirmed in the spa1
      det1-1 double mutant which carries a strong allele of det1. Taken together, these
      results show that SPA1 and DET1 act together to control photomorphogenesis
      throughout plant development. Hence, this suggests that COP1/SPA complexes and
      the CDD complex co-act in controlling the protein stability of COP1/SPA target
      proteins.

PMID- 20041286
TI  - Efficiency of hyaluronic acid (HA) sperm selection.
AB  - PURPOSE: Hyaluronic Acid (HA) has a role as "physiologic selector" for
      spermatozoa prior to intracytoplasmic sperm injection (ICSI). The objective of
      this study is to analyze the results achievable by the introduction of a routine
      HA-ICSI programme. METHODS: We retrospectively observed 293 couples treated with
      HA-ICSI versus 86 couples treated with conventional PVP-ICSI (historical control
      group). ICSI was performed on a limited number of oocytes per patient (1-3)
      according to Italian IVF law at the time of the study. Main outcome measures
      observed were: fertilization, embryo quality, implantation and pregnancy.
      RESULTS: This study showed that Injection of HA-bound spermatozoa (HA-ICSI)
      significantly improves embryo quality and implantation. CONCLUSIONS: If wider
      multi-center randomized studies will confirm these beneficial effects on ICSI
      outcome, HA could be considered as a routine choice for "physiologic" sperm
      selection prior to ICSI.

PMID- 20041287
TI  - Polymorphisms of TCF7L2 and HHEX genes in Chinese women with polycystic ovary
      syndrome.
AB  - PURPOSE: This study was to evaluate whether polymorphisms of TCF7L2 (rs7903146)
      and HHEX (rs1111875) genes responsible for insulin secretion are associated with
      the polycystic ovary syndrome (PCOS) in Chinese people. METHODS: 326 PCOS
      patients and 290 healthy individuals as controls were studied. Blood samples were
      obtained for DNA analyses and hormone measurements. Genotyping of the TCF7L2
      (rs7903146) and HHEX (rs1111875) genes was carried out by the polymerase chain
      reaction-restriction fragment length polymorphism method. RESULTS: We did not
      find statistically significant differences in the distribution of the TCF7L2
      rs7903146 and HHEX rs1111875 polymorphisms between the Chinese women with PCOS
      and the controls. Levels of hormones such as insulin, FSH, LH, LH/FSH, P, T and
      E2 were also similar between the different genotypes of the genes TCF7L2 and
      HHEX, respectively, which was confirmed within either the PCOS subjects or
      controls. CONCLUSIONS: There was no association of either of the two variants,
      rs7903146 of TCF7L2 and rs1111875 of HHEX, with the occurrence of PCOS in the
      Chinese population.

PMID- 20041288
TI  - Comment on Checa MA et al. J Assist Reprod Genet DOI 10.1007/s10815-009-9328-4.

PMID- 20041289
TI  - Interactions of prion protein with intracellular proteins: so many partners and
      no consequences?
AB  - Prion protein (PrP) plays a key role in the pathogenesis of transmissible
      spongiform encephalopathies (TSEs)--fatal diseases of the central nervous system.
      Its physiological function as well as exact role in neurodegeneration remain
      unclear, hence screens for proteins interacting with PrP seem to be the most
      promising approach to elucidating these issues. PrP is mostly a plasma membrane
      anchored extracellular glycoprotein and only a small fraction resides inside the
      cell, yet the number of identified intracellular partners of PrP is comparable to
      that of its membranal or extracellular interactors. Since some TSEs are
      accompanied by significantly increased levels of cytoplasmic PrP and this
      fraction of the protein has been found to be neurotoxic, it is of particular
      interest to characterize the intracellular interactome of PrP. It seems
      reasonable that at elevated cytoplasmic levels, PrP may exert cytotoxic effect by
      affecting the physiological functions of its intracellular interactors. This
      review is focused on the cytoplasmic partners of PrP along with possible
      consequences of their binding.

PMID- 20041290
TI  - Biological mechanisms of physical activity in preventing cognitive decline.
AB  - In order to guarantee better conditions for competition, the nervous system has
      developed not only mechanisms controlling muscle effectors, but also retrograde
      systems that, starting from peripheral structures, may influence brain functions.
      Under such perspective, physical activity could play an important role in
      influencing cognitive brain functions including learning and memory. The results
      of epidemiological studies (cross-sectional, prospective and retrospective)
      support a positive relationship between cognition and physical activities. Recent
      meta-analysis confirmed a significant effect of exercise on cognitive functions.
      However, the biological mechanisms that underlie such beneficial effects are
      still to be completely elucidated. They include supramolecular mechanisms (e.g.
      neurogenesis, synaptogenesis, and angiogenesis) which, in turn, are controlled by
      molecular mechanisms, such as BDNF, IGF-1, hormone and second messengers.

PMID- 20041291
TI  - The genome-wide expression profile of electroacupuncture in DNP-KLH immunized
      mice.
AB  - Previously, we demonstrated that electoracupuncture (EA) suppressed allergic
      reactions in DNP-KLH immunized mice. In this study, the mechanisms by which EA
      induces immunomodulation in the immunized mice were evaluated by genome-wide
      microarray analysis. The anti-allergic effects of EA in DNP-KLH immunized mice
      were confirmed by analyzing antigen specific IgE using ELISA. Microarray
      analysis, followed by real time RT-PCR validation, revealed that Th1 and Th17
      cytokine-, opioid peptide-, and anti-apoptosis-related genes were up-regulated
      upon treatment with EA. In addition, significant decreases in Th2 cytokine-, MAPK
      signaling pathway-, and apoptosis-related genes were observed following EA
      treatment.

PMID- 20041292
TI  - Cytotoxicity and enzymatic activity inhibition in cell lines treated with novel
      iminosugar derivatives.
AB  - Iminosugars are monosaccharide analogues that have been demonstrated to be
      specific inhibitors for glycosidases and are currently used therapeutically in
      several human disorders. N-alkylated derivatives of D-fagomine and (2R,3S,4R,5S)
      2-(hydroxymethyl)-5-methylpyrrolidine-3,4-diol with aliphatic chains were tested
      in eight human cancer cell lines to analyze their cytotoxicity and the inhibitory
      effect in the activities of specific glycosidases. Results indicate that these
      compounds were more cytotoxic as the length of the alkyl chain increases. N
      dodecyl-D-fagomine inhibited specifically the alpha-D-glucosidase activity in
      cell lysates, whereas no effect was detected in other glycosidases. The N-dodecyl
      derivative of (2R,3S,4R,5S)-2-(Hydroxymethyl)-5-methylpyrrolidine-3,4-diol
      induced specific inhibition against alpha-L-fucosidase in cell lysates. Our
      results indicated that the length of the alkyl chain linked to the iminosugars
      determine their cytotoxicity as well as the inhibitory effect on the enzymatic
      activities of specific glycosidases, in human cancer cell lines.

PMID- 20041293
TI  - Human serotonin transporter expression during megakaryocytic differentiation of
      MEG-01 cells.
AB  - The serotonin (5-HT) transporter (SERT) has been found altered in platelets of
      patients with genetically complex disorders, including mood-anxiety, pain and
      eating disorders. In this study, we used cell cultures of platelet precursors as
      models of investigation on mechanisms of SERT regulation: SERT expression was
      appraised during megakaryocytic differentiation of human megakaryoblastic MEG-01
      cells. Cells were cultured for 8 days with 10(-7)M 4-beta-12-tetradecanoylphorbol
      13-acetate (beta-TPA) in the presence of 10% fetal bovine serum (FBS) and SERT
      was assessed by real time PCR, immunofluorescence microscopy, Western blot and
      [(3)H]5-HT re-uptake. Results revealed that SERT is present in control-untreated
      MEG-01 cells. beta-TPA-differentiating MEG-01 cells showed a redistribution of
      SERT fluorescence, diffuse to cell bodies and blebs along with a 3-fold SERT mRNA
      increase and a moderate raise in SERT protein (1.5/1.4-fold) by immunoblot and re
      uptake assays. In summary, we have shown herein that control megakaryoblasts
      express the SERT protein. SERT is modulated by differentiation events, implying
      that SERT density in platelets is under the control of megakaryocytopoiesis
      stages. Differentiation of MEG-01 cells can provide considerable insight into
      interactions between SERT genetics, transmitter-hormonal/homeostatic mechanisms
      and signaling pathways.

PMID- 20041294
TI  - Predicting miRNA's target from primary structure by the nearest neighbor
      algorithm.
AB  - We used a machine learning method, the nearest neighbor algorithm (NNA), to learn
      the relationship between miRNAs and their target proteins, generating a predictor
      which can then judge whether a new miRNA-target pair is true or not. We acquired
      198 positive (true) miRNA-target pairs from Tarbase and the literature, and
      generated 4,888 negative (false) pairs through random combination. A 0/1 system
      and the frequencies of single nucleotides and di-nucleotides were used to encode
      miRNAs into vectors while various physicochemical parameters were used to encode
      the targets. The NNA was then applied, learning from these data to produce a
      predictor. We implemented minimum redundancy maximum relevance (mRMR) and
      properties forward selection (PFS) to reduce the redundancy of our encoding
      system, obtaining 91 most efficient properties. Finally, via the Jackknife cross
      validation test, we got a positive accuracy of 69.2% and an overall accuracy of
      96.0% with all the 253 properties. Besides, we got a positive accuracy of 83.8%
      and an overall accuracy of 97.2% with the 91 most efficient properties. A web
      server for predictions is also made available at
      http://app3.biosino.org:8080/miRTP/index.jsp.

PMID- 20041295
TI  - Massive gastric dilatation and anuria resolved with naso-gastric tube
      decompression.
AB  - We report for the first time a case of acute kidney injury associated with severe
      gastric distention after a laparoscopic Nissen-Rossetti fundoplication of the
      stomach for hiatal hernia. An abdominal compartment syndrome secondary to intra
      abdominal hypertension was suspected. Naso-gastric tube decompression resulted in
      immediate resaturation of the diuresis and progressive recovery of renal
      function.

PMID- 20041298
TI  - Multiscale time irreversibility of heartbeat at rest and during aerobic exercise.
AB  - The multiscale time irreversibility (MTI) involves the lack of consistency in the
      properties of a time series if one reverses the reading direction along the time.
      To analyze the RR time series at rest and during aerobic exercise through the
      MTI, both in healthy people and cardiac patients. The heartbeat signal was
      recorded beat to beat for 15 min at rest and 15 min while pedalling on a static
      bicycle in 10 healthy and active men (age 26.5 +/- 3.3 years; height 179.3 +/-
      6.6 cm; weight 80.4 +/- 11.8 kg) and 10 cardiac patients (age 61.1 +/- 4.7 years,
      height 165.3 +/- 5.3 cm; weight 86.9 +/- 11.1 kg). The MTI was calculated through
      the asymmetry index (AI), defined as the sum of the values of asymmetry obtained
      for each scale from 1 to 10. The AI decreases significantly in healthy subjects
      from 0.51 +/- 0.28 at rest to 0.28 +/- 0.24 during exercise (P = 0.01) but not in
      cardiac patients (-0.2204 +/- 0.5097 at rest and 0.0848 +/- 0.1200 during
      exercise; P = 0.07). MTI distinguish adequately the four experimental situations
      because it can be considered as an index of the internal property of the signal
      in contrast to linear methods which are highly sensitive to external influences
      over the heart rhythm, particularly sympathetic and parasympathetic stimuli.

PMID- 20041296
TI  - Vascular calcification score on plain radiographs of the feet as a predictor of
      peripheral arterial disease in patients with chronic kidney disease.
AB  - BACKGROUND: The incidence of lower extremity amputation is increasing in patients
      with chronic kidney disease (CKD), but symptoms of peripheral arterial disease
      (PAD) in patients with CKD are uncommon. The aim of the current study was to
      assess the value of the vascular calcification (VC) score on plain radiographs of
      the feet for the prediction of PAD in patients with CKD. METHODS: We recruited
      102 patients with CKD (24 pre-dialysis, 58 hemodialysis [HD], and 20 peritoneal
      dialysis [PD]). We defined the VC score on the plain radiographs of the feet as
      follows: score 0, no calcification; score 1, the length of the VC is <5 cm in a
      single foot or <2 cm in both feet; and score 2, the length of the VC is >5 cm in
      a single foot or >2 cm in both feet. We evaluated the atherosclerotic calcified
      plaques of the femoral or popliteal artery with Doppler ultrasonography and
      compared it with the VC score. RESULTS: Patients with high VC scores showed more
      atherosclerotic calcified plaques in the femoral or popliteal artery (P < 0.01).
      The prevalence of PAD in patients with CKD was closely related with the VC score
      (P < 0.01). PAD was associated with diabetes, a higher hsCRP, and a lower total
      cholesterol level (P < 0.01). The VC score was a significant predictor of the
      presence of PAD (odds ratio: 6.66, P < 0.001). CONCLUSIONS: Asymptomatic CKD
      patients, including those on HD and PD, may have PAD and routine testing by plain
      radiographs of the feet followed by Doppler ultrasonography are of pivotal
      significance, especially if the patients are diabetic.

PMID- 20041299
TI  - Identity with Jesus Christ: the case of Leon Gabor.
AB  - From July 1, 1959 to August 15, 1961, Milton Rokeach studied three male patients
      at Ypsilanti State Hospital who believed that they were Jesus Christ. They met
      regularly together with Rokeach and his research staff, a procedure designed to
      challenge their delusional systems. He believed that Leon Gabor, the youngest of
      the three, would be the most likely to abandon his delusional beliefs. Instead,
      Leon met the challenges that the procedure posed by creative elaborations of his
      delusional system, especially through the adoption of a new name that gave the
      initial appearance of the abandonment of his Christ identity but in fact drew on
      aspects of the real Jesus Christ's identity that were missing from his earlier
      self-representation.

PMID- 20041300
TI  - Sculpturing digit shape by cell death.
AB  - Physiological cell death is a key mechanism that ensures appropriate development
      and maintenance of tissues and organs in multicellular organisms. Most structures
      in the vertebrate embryo exhibit defined areas of cell death at precise stages of
      development. In this regard the areas of interdigital cell death during limb
      development provide a paradigmatic model of massive cell death with an evident
      morphogenetic role in digit morphogenesis. Physiological cell death has been
      proposed to occur by apoptosis, cellular phenomena genetically controlled to
      orchestrate cell suicide following two main pathways, cytochrome C liberation
      from the mitochondria or activation of death receptors. Such pathways converge in
      the activation of cysteine proteases known as caspases, which execute the cell
      death program, leading to typical morphologic changes within the cell, termed
      apoptosis. According to these findings it would be expected that caspases loss of
      function experiments could cause inhibition of interdigital cell death promoting
      syndactyly phenotypes. A syndactyly phenotype is characterized by absence of
      digit freeing during development that, when caused by absence of interdigital
      cell death, is accompanied by the persistence of an interdigital membrane.
      However this situation has not been reported in any of the KO mice or chicken
      loss of function experiments ever performed. Moreover histological analysis of
      dying cells within the interdigit reveals the synchronic occurrence of different
      types of cell death. All these findings are indicative of caspase alternative
      and/or complementary mechanisms responsible for physiological interdigital cell
      death. Characterization of alternative cell death pathways is required to explain
      vertebrate morphogenesis. Today there is great interest in cell death via
      autophagy, which could substitute or act synergistically to the apoptotic
      pathway. Here we discuss what is known about physiological cell death in the
      developing interdigital tissue of vertebrate embryos, paying special attention to
      the avian species.

PMID- 20041301
TI  - Apoptosis in pre-Bilaterians: Hydra as a model.
AB  - Hydra is a member of the ancient metazoan phylum Cnidaria and is an especially
      well investigated model organism for questions of the evolutionary origin of
      metazoan processes. Apoptosis in Hydra is important for the regulation of
      cellular homeostasis under different conditions of nutrient supply. The molecular
      mechanisms leading to apoptosis in Hydra are surprisingly extensive and
      comparable to those in mammals. Genome wide sequence analysis has revealed the
      presence of large caspase and Bcl-2 families, the apoptotic protease activating
      factor (APAF-1), inhibitors of apoptotic proteases (IAPs) and components of a
      putative death receptor pathway. Regulation of apoptosis in Hydra may involve BH
      3 only proteins and survival pathways, possibly including insulin signalling.

PMID- 20041302
TI  - Gender differences in apoptotic signaling in heart failure due to volume
      overload.
AB  - This study examined sex differences in the regulation of pro- and anti-apoptotic
      proteins in cardiac hypertrophy and heart failure due to volume overload induced
      by arteriovenous (AV) shunt in rats. General characteristics and hemodynamic
      assessment revealed the presence of cardiac hypertrophy at 4 weeks of AV shunt in
      male (n = 12) and female (n = 12) rats, whereas heart failure was seen at 16
      weeks in male rats only. Although a decrease in apoptosis was seen in hearts of
      both sexes at 4 weeks, an increase in apoptosis in males and a reduction in the
      female heart were observed at 16 weeks of AV shunt. Unlike females, increases in
      the pro-apoptotic proteins, BAX, caspases 3 and 9 were seen in 16 weeks post-AV
      shunt in male rats. While an increase in phospho-Bad was detected, phospho-Bcl-2
      protein was decreased in males. Females showed an increase in only phospho-Bcl-2
      protein at 16 weeks post-AV shunt. Ovariectomy (n = 12) abolished the increase in
      phospho-Bcl-2 protein, but this was restored by treatment with 17-beta estradiol.
      These data suggest that downregulation of phospho-Bcl-2 and an upregulation of
      BAX may play a major role in cardiomyocyte apoptosis in heart failure due to
      volume overload in male rats. Furthermore, upregulation of phospho-Bcl-2 in the
      heart due to estrogen may confer resistance against cardiomyocyte apoptosis in
      females.

PMID- 20041303
TI  - Cellular responses to etoposide: cell death despite cell cycle arrest and repair
      of DNA damage.
AB  - The topoisomerase IIalpha inhibitor etoposide is a 'broad spectrum' anticancer
      agent and a potent inducer of DNA double strand breaks. DNA damage response of
      mammalian cells usually involves cell cycle arrest and DNA repair or, if
      unsuccessful, cell death. We investigated these processes in the human colon
      cancer cell line HT-29 treated with three different etoposide regimens mimicking
      clinically relevant plasma concentrations of cancer patients. Each involved a
      period of drug-free incubation following etoposide exposure to imitate the
      decline of plasma levels between the cycles of chemotherapy. We found a massive
      induction of double strand breaks that were rapidly and nearly completely fixed
      long before the majority of cells underwent apoptosis or necrosis. An even
      greater percentage of cells lost clonogenicity. The occurrence of double strand
      breaks was accompanied by a decrease in the levels of Ku70, Ku86 and DNA-PK(cs)
      as well as an increase in the level of Rad51 protein. Twenty-four hours after the
      first contact with etoposide we found a pronounced G(2)/M arrest, regardless of
      the duration of drug exposure, the level of double strand breaks and the extent
      of their repair. During the subsequent drug-free incubation period, the loss of
      clonogenicity correlated well with the preceding G(2)/M arrest as well as with
      the amount of cell death found several days after exposure. However, it
      correlated neither with early apoptosis or necrosis nor with any of the other
      investigated parameters. These results suggest that the G(2)/M arrest is an
      important determinant in the cytostatic action of etoposide and that the removal
      of DNA double strand breaks is not sufficient to ensure cell survival.

PMID- 20041304
TI  - Comprehensive evaluation of CT pulmonary angiography for patients suspected of
      having pulmonary embolism.
AB  - Recently, CT pulmonary angiography (CTPA), especially performed with multi
      detector row CT, has become a key imaging modality for pulmonary embolism.
      However, CTPA that was performed under clinical suspicion of pulmonary embolism
      has been shown to lead to high prevalence of alternative diagnosis, up to 25.4%.
      A comprehensive evaluation of pulmonary and extrapulmonary abnormalities
      including cardiovascular lesions is critical in proper diagnosis and patient
      care. Radiologists should be familiar with the comprehensive interpretation of
      CTPA to facilitate differential diagnosis and further treatment decision.

PMID- 20041305
TI  - Sympathetic dysfunction of systemic right ventricle in congenitally corrected
      transposition of the great arteries.
AB  - We evaluate the systemic right ventricle (SRV) failure of congenitally corrected
      transposition of the great arteries using the scintigraphic studies in a case
      with 32-year-old male who improved the heart failure by the use of beta
      adrenergic blockers. The myocardial perfusion sympathetic nervous system activity
      mismatch with preserved coronary flow and wall thickness indicates a distinctive
      feature as SRV cardiomyopathy, suggesting the importance of recovery of SRV
      sympathetic dysfunction for improving the prognosis.

PMID- 20041306
TI  - Predictors of response to cardiac resynchronization therapy: the holy grail of
      electrophysiology.

PMID- 20041307
TI  - The analysis of longitudinal quality of life measures with informative drop-out:
      a pattern mixture approach.
AB  - PURPOSE: The analysis of longitudinal health-related quality of life measures
      (HRQOL) can be seriously hampered due to informative drop-out. Random effects
      models assume Missing At Random and do not take into account informative drop
      out. We therefore aim to correct the bias due to informative drop-out. METHODS:
      Analyses of data from a trial comparing standard-dose and high-dose chemotherapy
      for patients with breast cancer with respect to long-term impact on HRQOL will
      serve as illustration. The subscale Physical Function (PF) of the SF36 will be
      used. A pattern mixture approach is proposed to account for informative drop-out.
      Patterns are defined based on events related to HRQOL, such as death and relapse.
      The results of this pattern mixture approach are compared to the results of the
      commonly used random effects model. RESULTS: The findings of the pattern mixture
      approach are well interpretable, and different courses over time in different
      patterns are distinguished. In terms of estimated differences between standard
      dose and high dose, the results of both approaches are slightly different, but
      have no consequences for the clinical evaluation of both doses. CONCLUSION: Under
      the assumption that drop-out is at random within the patterns, the pattern
      mixture approach adjusts the estimates to a certain degree. This approach
      accounts in a relatively simple way for informative drop-out.

PMID- 20041308
TI  - Identification of the first case of germline duplication of BRCA1 exon 13 in an
      Italian family.
AB  - In this work we report for the first time a family in Italy with the BRCA1
      ins6kbEx13 mutation, a recurrent founder mutation originating from northern
      Britain. After the initial identification of exon 13 duplication by multiplex
      ligation-dependent probe amplification (MLPA assay), we confirmed the identity of
      the alteration with the previously published BRCA1 ins6kbEx13 mutation, by
      mutation specific PCR and RT-PCR assays and by haplotype analysis. As rarely
      reported previously, the MLPA assay was also used to examine DNA from formalin
      fixed paraffin embedded (FFPE) normal tissues of other affected subjects in the
      family and it was the only effective method to perform a complete segregation
      analysis of the BRCA1 ins6kbEx13 mutation in the family. A combination of
      different approaches including MLPA analysis, haplotype analysis and LOH study on
      tumor samples of all the affected members allowed to reassess the maternal
      transmission of the mutation expected by the pedigree analysis. Moreover,
      detailed morphological analysis of breast cancers of BRCA1 ins6kbEx13 mutation
      carriers demonstrated a rare histological variant of breast carcinomas that has
      never been described in patients carrying BRCA1 mutations. Our study confirms the
      MLPA technique as a reliable and effective method for a primary screening for
      BRCA1 rearrangements also by using FFPE tissues and strongly suggests that histo
      pathological, immunonohistochemical and molecular information from FFPE tumor
      tissues should be more often considered and integrated into routine diagnostic
      practice of hereditary tumors.

PMID- 20041309
TI  - Prevalence and incidence of HCV infection among Vietnam heroin users with recent
      onset of injection.
AB  - HCV infection continues to spread at an alarming rate among IDU populations. The
      available evidence suggests that HCV is acquired relatively quickly following
      onset of injection. However, there are few prospective studies of HCV
      acquisition, particularly among IDU populations in resource-poor settings. A
      sample of young male heroin injectors with recent onset of injection (<4 years)
      was recruited in Hanoi, Vietnam for a prospective assessment of the early course
      of injection (n = 179). Both behavioral and biological assessments (including
      detailed retrospective assessment of injection initiation) were conducted at
      baseline and repeated at 6-month intervals for a period of 16 months. Variables
      associated with HCV infection (p value < 0.05) in bivariate analyses were
      considered for inclusion in logistic regression models to identify risk factors
      independently associated with HCV infection. HCV incidence was calculated by
      using the incidence density approach and was expressed in terms of person-years
      of observation. The baseline of prevalence of HCV was 46%. HCV significantly
      increased in relation to time since first injection, from 30% in subjects with
      </=10 months of injection risk to 70% in subjects with >/=30 months injection
      risk (p value = 0.0005). In multivariate logistic regression analysis, increasing
      age, incarceration in a drug detention facility (OR = 2.54; 95%CI 1.05, 6.15),
      and time since first injection remained significantly associated with HCV
      infection. Use of injection as primary mode of administration (OR = 2.56; 95%CI
      0.98, 6.69) achieved marginal significance. After 16 months of follow-up, the
      incidence rate of HCV was 23.35 per 100 person-years and the mean time between
      first injection and first positive HCV test was 1.2 years. HCV is acquired much
      more rapidly among new injector populations than previously recognized,
      demonstrating the need for early behavioral intervention among new heroin-user
      populations. Particularly critical are interventions that target new heroin user
      populations, including interventions that improve understanding of viral
      transmission dynamics, that promote alternative strategies for drug sharing, and
      that delay initiation of injection.

PMID- 20041310
TI  - Increase in intrathoracic volume in pectus excavatum patients after the Nuss
      procedure.
AB  - In this study, we present finite element analysis models to calculate the
      increase in intrathoracic volume of pectus excavatum patients after the Nuss
      procedure. One virtue of our approach is that the measurement of the
      intrathoracic volume has no time difference and is not affected by postoperative
      pain, which cannot be achieved with a 2-year difference between pre- and
      postoperative pulmonary function testing or any other clinical method. The
      calculations show that the intrathoracic volume of pectus excavatum patients
      increased by approximately 2.72-8.88% after the Nuss procedure. The increment
      curve was patient-dependent, although the increment behavior was similar among
      the six patients examined. The curve of the increase became flat when the
      elevating force exceeded 80 N or the displacement of the lower sternal end
      exceeded 2.6 cm in half of our cases.

PMID- 20041311
TI  - Comparison of feature selection and classification methods for a brain-computer
      interface driven by non-motor imagery.
AB  - The aim of this study was to compare methods for feature extraction and
      classification of EEG signals for a brain-computer interface (BCI) driven by
      auditory and spatial navigation imagery. Features were extracted using
      autoregressive modeling and optimized discrete wavelet transform. The features
      were selected with exhaustive search, from the combination of features of two and
      three channels, and with a discriminative measure (r (2)). Moreover, Bayesian
      classifier and support vector machine (SVM) with Gaussian kernel were compared.
      The results showed that the two classifiers provided similar classification
      accuracy. Conversely, the exhaustive search of the optimal combination of
      features from two and three channels significantly improved performance with
      respect to using r(2) for channel selection. With features optimally extracted
      from three channels with optimized scaling filter in the discrete wavelet
      transform, the classification accuracy was on average 72.2%. Thus, the choice of
      features had greater impact on performance than the choice of the classifier for
      discrimination between the two non-motor imagery tasks investigated. The results
      are relevant for the choice of the translation algorithm for an on-line BCI
      system based on non-motor imagery.

PMID- 20041313
TI  - Clinical feasibility of a magnetic resonance tracking system to guide the
      position of the scan plane during physiologic joint motion.
AB  - PURPOSE: Unrestricted physiologic joint motion results in multidirectional
      displacement of the anatomic structures. When performing real-time magnetic
      resonance (MR) imaging of such a joint motion, continuous adjustment of the scan
      plane position may be required. The purpose of this study was to evaluate the
      clinical feasibility of a method to guide the scan plane position during dynamic
      motion MR imaging of freely moving joints. MATERIALS AND METHODS: The location of
      a small tracker device (dedicated hardware) placed on the patient's skin
      overlying a joint was determined by an ultrashort MR sequence and used to
      automatically adjust the scan plane position prior to each dynamic-motion MR
      image. Using a vertically open MR unit, this MR tracking system was applied in
      ten dynamic-motion MR examinations to evaluate flexion/extension manoeuvres in
      the weight-bearing knee joint, and in ten dynamic-motion MR examinations of the
      shoulder joint to evaluate manoeuvres such as internal/external rotation of the
      humerus, stress testing of the glenohumeral joint and abduction/adduction
      manoeuvres. Average number of manoeuvre repetitions, total number of images and
      percentage of useful images per manoeuvre were calculated. Imaging time per scan
      plane for each manoeuvre was recorded. RESULTS: Average repetition of manoeuvres
      varied between 1.6 and 5.8, with an average number of 7 to 18 images per
      manoeuvre. Average percentage of useful images varied between 61% and 89%. Total
      imaging time per scan plane ranged between 1 min 10 s and 4 min 51 s.
      CONCLUSIONS: The MR tracking system to guide the slice position for each
      consecutive dynamic-motion MR image of the freely but slowly moving shoulder or
      knee joint was feasible for clinical use, providing a high percentage of useful
      images for each manoeuvre within a clinically acceptable time frame.

PMID- 20041312
TI  - Interventional navigation systems for treatment of unresectable liver tumor.
AB  - Most patients with liver tumors are not candidates for surgical resection. A
      number of local treatment methods for unresectable liver tumors have recently
      received considerable interests. The major task of these procedures is accurate
      needle placement with the aim of complete tumor removal and minimal damage to
      surrounding normal liver parenchyma. In this article, we review the current
      status of interventional navigation system (INS) for treatment of unresectable
      liver tumors in terms of overall workflow, tracking systems, and research
      development. The conceptual design of INS consists of pre-operative and intra
      operative modules. The tracking system falls into three types: optical,
      electromagnetic, and MR gradient based. The current INS, according to their image
      modalities, can be classified into four categories: MRI based, CT based, U/S
      based, and multimodalities based. The article also discusses the future research
      direction for enhanced performance of INS with real time imaging, high accuracy,
      high resolution, and friendly user-interface.

PMID- 20041314
TI  - The content of selected chemical elements in the hair of young men of the Bantu
      language group from Tanzania versus environmental and social conditioning.
AB  - Research works that would determine the content of chemical elements in black
      population organisms on the basis of hair analysis are not numerous. There are no
      studies referring to black populations living in indigenous environment, like the
      Mafinga region, Iringa District in Tanzania examined by us. The aim of the study
      performed was to analyse the content of chemical elements Fe, Ca, Mg, Zn and Cu
      in easily available biological media like hair. The material was collected in
      October 2005 and March 2006 during anthropological examination, which came from
      young males (n = 91), students of a secondary school. Large Ca concentration
      range was found for the total number of subjects (680.20 to 2,089.70 ug/g d.m.).
      Mean Fe content in hair for the total number of subjects was 11.19 +/- 3.70 ug/g
      d.m., while that of Mg 6.84 +/- 2.02 ug/g d.m. Mean Zn concentration for the
      total number of subjects was 91.06 +/- 39.22 ug/g d.m., being significantly
      higher in younger group than in older one (p = 0.039). Mean Cu concentration in
      hair for the total number of subjects was 7.50 +/- 2.90 ug/g d.m Body mass index
      (BMI = kg/m2) was calculated for the subjects showing that out of 91 men
      participating in the study 15.4% was characterised by mediocre nutrition. No
      statistically significant correlations were found between BMI and the analysed
      chemical elements. The analysis of the content of trace elements in the hair of
      the examined young males showed deficiencies in Zn, Cu, Fe and significantly in
      Mg.

PMID- 20041315
TI  - FRAT1 expression and its correlation with pathologic grade, proliferation, and
      apoptosis in human astrocytomas.
AB  - FRAT1 was originally characterized as a protein frequently rearranged in advanced
      T-cell lymphoma, which inhibits GSK-3-mediated phosphorylation of beta-catenin
      and positively regulates the Wnt signaling pathway. FRAT1 has recently been
      identified as a proto-oncogene involved in tumorigenesis, as elevated expression
      of FRAT1 was detected in several types of human cancers. However, the
      relationship between FRAT1 and human astrocytomas is unclear. In this study, we
      detected the expression of FRAT1 in 76 patients with human astrocytoma by
      immunohistochemistry. The proliferative index (PI) of tumor cells was evaluated
      by Ki-67 staining, and the apoptotic index (AI) was determined by fluorometric
      TdT-mediated dUTP nick end labeling (TUNEL) assay. The results showed that the
      FRAT1 immunoreactivity score (IRS), PI, and AI of astrocytoma were 4.11 +/- 3.86,
      31.92 +/- 20.00%, and 2.66 +/- 1.66%, respectively, and all of them increased
      markedly with the increase of pathologic grade of astrocytomas (P < 0.001 for
      all). The PI in the FRAT1-positive group was significantly higher than that in
      the FRAT1-negative group (P < 0.001). In addition, the PI was positively
      correlated with FRAT1 IRS (P < 0.001). Although there was no significant
      difference between the AI in the FRAT1-positive group and that in the FRAT1
      negative group (P = 0.123), the AI was inversely correlated with FRAT1 IRS (P =
      0.022). In conclusion, FRAT1 may be an important factor in the tumorigenesis and
      progression of astrocytoma, which could be used as a potential biomarker for
      pathological diagnosis of malignancy and a target for biological therapy.

PMID- 20041316
TI  - May metaplastic breast carcinomas be actually basal-like carcinoma? Further
      evidence study with its ultrastructure and survival analysis.
AB  - Metaplastic breast carcinoma (MBC) encompasses a heterogeneous group of tumors.
      Based upon the microarray of MBCs, these tumors showed features of basal-like
      carcinoma and myoepithelial differentiation. However, MBCs entity still remained
      unclear. So we performed a systematic research to explicit metaplastic breast
      carcinomas further. A panel of ER, PR, HER-2, CK5/6, CK14, P63 and EGFR were
      prepared for detection of MBCs, and fluorescence in situ hybridization for HER-2
      gene amplification and ultrastructure observation were also performed.
      Sensitiveness between CK5/6 and other antibodies in diagnosis was analysed, and
      survival analysis was also carried out. ER, PR and HER-2 were negative. CK5/6
      (12/12), CK14 (9/12), EGFR (10/12) and P63 (8/12) were positive. FISH for HER-2
      displayed no amplification (ratio values < 1.8). Ultrastructure showed
      tonofibrils, thin filament and dense body in the cytoplasm. Significant
      statistical differences were detected between groups (F = 8.080, P = 0.000) of
      score of CK5/6, CK14, P63 and EGFR. Significant statistical differences were also
      detected between age and lymph node involvement and survival (chi(2) = 10.835, P
      = 0.004). MBCs may be actually basal-like carcinomas. In the diagnosis of MBCs,
      CK5/6, CK14, P63 and EGFR may be effective and CK5/6 may be more sensitive than
      CK14 and P63. Survival of MBCs may be associated with age and lymph node
      involvement. However, given the limitations of our research accumulated cases,
      prospective clinicopathologic studies are needed to further elucidate MBCs.

PMID- 20041317
TI  - Inhibition of autophagy by 3-MA potentiates cisplatin-induced apoptosis in
      esophageal squamous cell carcinoma cells.
AB  - Cisplatin (DDP)-based adjuvant chemotherapy is widely used for the treatment of
      esophageal cancer. However, DDP resistance has become more common and thus new
      approaches are required to be explored. Cisplatin was used to induce autophagy in
      the human esophageal cancer cell line, EC9706 cells, and the effect of autophagy
      on the survival of EC9706 cells was investigated using an autophagy inhibitor 3
      MA. Cell viability was measured by CCK8 assay. Apoptosis and cell cycle were
      detected by flow cytometry. Monodansylcadaverine (MDC) was used to detect
      autophagy. Western blotting assay was used to investigate the molecular changes
      that occurred in the course of treatment. DDP inhibited cell proliferation,
      induced cell death and cell cycle arrest at S phage. Moreover, autophagy was
      activated through class III PI3K pathway. The expression of autophagy-related
      Beclin1 and LC3-I was up-regulated and part of LC3-I was converted into LC3-II.
      However, after the combination treatment of 3-MA and DDP, the cell inhibitory
      rate increased; the apoptosis rate and the numbers of cells in S phase also
      increased. Furthermore, the accumulation of autophagic vacuoles was decreased;
      the expression of Beclin1 and LC3 was significantly down-regulated and the
      release of cytochrome c was decreased. DDP-induced apoptosis in EC9706 cells can
      be enhanced by the inhibitor of autophagy, 3-MA. Autophagy might play a role as a
      self-protective mechanism in DDP-treated esophageal cancer cells, and its
      inhibition could be a novel strategy for the adjuvant chemotherapy of esophageal
      cancer.

PMID- 20041318
TI  - The impact of trastuzumab on radiation-induced pulmonary fibrosis: results of an
      experimental study.
AB  - There are no data regarding the late toxicity of trastuzumab (T) administration
      with radiotherapy (RT). In this experimental study, we aimed to asses if
      concurrent or sequential administration of T has any impact for the development
      of radiation-induced pulmonary fibrosis in rats. Fifty-four female Wistar-albino
      rats were divided into 6 groups. First group of rats (Group 1; concurrent T) had
      irradiation to whole thoracic region concurrently with T. Second group (Group 2:
      sequential T-RT) received thoracic irradiation, 1 week after T. Third group
      (Group 3: sequential RT-T) had thoracic irradiation first and they had T
      injection 1 week after RT. Fourth group (Group 4: T only) had only T application.
      Fifth group (Group 5: RT) had only RT. The last group (Group 6: sham) of rats
      were observed without any application. A single dose of 12 Gy was given to both
      lungs with an anterior field at 2 cm depth. T dose which was equivalent to 6
      mg/kg adult dose was calculated for each rat, and injected by the tail vein. As
      an end point the extent of pulmonary fibrosis for each field was graded on a
      scale from 0 (normal lung or minimal fibrous thickening) to 4 (total fibrous
      obliteration of the field) at histopathological examination. The mean value of
      fibrosis scores were 1.44, 1.77, 1.75 and 1.62 for Group 1, 2, 3 and 5,
      respectively, without any statistically significant differences among them
      (P>0.05). The mean value of fibrosis scores for Group 4 and 6 were 0.25 and 0.33,
      respectively (P>0.05). When the mean value of fibrosis scores of the groups which
      had RT with or without T, compared with the observation and the T only groups,
      the difference was significant (P<0.05) (one-way ANOVA and Tukey HSD post hoc
      tests) As a conclusion: addition of T to thoracic irradiation either sequentially
      or concomitantly did not increase radiation-induced pulmonary fibrosis in rats.

PMID- 20041319
TI  - Discovery of a set of biomarkers of human lung adenocarcinoma through cell-map
      proteomics and bioinformatics.
AB  - Carcinogenesis of lung adenocarcinoma remains unclear and very few biomarkers
      have been accepted for routine clinical use. In order to explore the pathogenesis
      and screen ideal biomarkers, we conducted cell-map proteomics study in human lung
      adenocarcinoma. Homogeneous lung adenocarcinoma cells were purified by laser
      capture microdissection (LCM). A high performance liquid chromatography (HPLC)
      system was used to separate the total solution proteins. The resulting MS/MS
      spectra were automatically searched for proteins against IPI human protein
      database using the TurboSEQUEST searching engine. Physico-chemical properties of
      the identified proteins, including molecular weight (MW), isoelectric point (PI),
      were described based on various proteomics web server and statistical analysis.
      Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
      were used to analyze function of expressed proteins and screen candidate
      biomarkers according to biological annotation. A total of 843 distinct proteins
      were identified and were categorized as 10 sorts of molecular function and 17
      sorts of biological process based on GO annotation. Further searching against
      KEGG pathways found that six proteins were involved in WNT signaling pathway,
      apoptosis pathway, Erb-2 signaling pathway, p53 signaling pathway, ubiquitin
      mediated proteolysis and were might be hopefully screened as candidate markers of
      lung adenocarcinoma. The present study through LCM and cell-map proteomics showed
      a full view on the expressed protein profiles of lung adenocarcinoma. Several
      candidate markers are hopeful to be used as molecular targets of diagnosis,
      treatment and prognosis of lung adenocarcinoma.

PMID- 20041320
TI  - Biology and pathology of glia: an update.

PMID- 20041322
TI  - Pharmacokinetics of intravenous omeprazole in critically ill paediatric patients.
AB  - The proton pump inhibitors are first-line drugs for the treatment of a number of
      gastrointestinal diseases. These drugs have a good safety profile, making it
      possible to use them in paediatric patients. Although their pharmacokinetics in
      children has not been extensively studied, research performed suggests that the
      dose used should be varied as a function of age, as this factor affects the
      drug's metabolism. Proton pump inhibitors can be used in critically ill children
      for the prophylaxis and treatment of gastrointestinal haemorrhage, although there
      is still little experience with this. The most widely used proton pump inhibitor
      at the present time is omeprazole. As there are specific characteristics of these
      patients that could alter the pharmacokinetics of the drugs, studies need to be
      performed to determine the most suitable dose and dosage interval.

PMID- 20041321
TI  - Ivermectin is a nonselective inhibitor of mammalian P-type ATPases.
AB  - Ivermectin is a large spectrum antiparasitic drug that is very safe at the doses
      actually used. However, as it is being studied for new applications that would
      require higher doses, we should pay attention to its effects at high
      concentrations. As micromolar concentrations of ivermectin have been reported to
      inhibit the sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA), we decided to
      investigate its putative inhibitory effect on other two important P-type ATPases,
      namely the Na(+) , K(+)-ATPase and H(+)/K(+)-ATPase. We first extended the data
      on SERCA, using preparations from rat enriched in SERCA1a (extensor digitorum
      longus) and 1b (heart) isoforms. Secondly, we tested the effect of ivermectin in
      two preparations of rat Na(+), K(+)-ATPase in order to appreciate its putative
      selectivity towards the alpha(1) isoform (kidney) and the alpha(2)/alpha(3)
      isoforms (brain), and in an H(+)/K(+)-ATPase preparation from rat stomach.
      Ivermectin inhibited all these ATPases with similar IC(50) values (6-17 microM).
      With respect to the inhibition of the Na(+), K(+)-ATPase, ivermectin acts by a
      mechanism different from the classical cardiac glycosides, based on selectivity
      towards the isoforms, sensibility to the antagonistic effect of K(+) and to ionic
      conditions favoring different conformations of the enzyme. We conclude that
      ivermectin is a nonselective inhibitor of three important mammalian P-type
      ATPases, which is indicative of putative important adverse effects if this drug
      were used at high doses. As a consequence, we propose that novel analogs of
      ivermectin should be developed and tested both for their parasitic activity and
      in vitro effects on P-type ATPases.

PMID- 20041323
TI  - Morphological response of Typha domingensis to an industrial effluent containing
      heavy metals in a constructed wetland.
AB  - Typha domingensis had become the dominant species after 2 years of operation of a
      wetland constructed for metallurgical effluent treatment. Therefore, the main
      purpose of this study was to investigate its ability to tolerate the effluent and
      to maintain the contaminant removal efficiency of the constructed wetland. Plant,
      sediment, and water at the inlet and outlet of the constructed wetland and in two
      natural wetlands were sampled. Metal concentration (Cr, Ni, and Zn) and total
      phosphorus were significantly higher in tissues of plants growing at the inlet in
      comparison with those from the outlet and natural wetlands. Even though the
      chlorophyll concentration was sensitive to effluent toxicity, biomass and plant
      height at the inlet and outlet were significantly higher than those in the
      natural wetlands. The highest root and stele cross-sectional areas, number of
      vessels, and biomass registered in inlet plants promoted the uptake, transport,
      and accumulation of contaminants in tissues. The modifications recorded accounted
      for the adaptability of T. domingensis to the conditions prevailing in the
      constructed wetland, which allowed this plant to become the dominant species and
      enabled the wetland to maintain a high contaminant retention capacity.

PMID- 20041324
TI  - Measurement and computation of movement of bromide ions and carbofuran in ridged
      humic-sandy soil.
AB  - Water flow and pesticide transport in the soil of fields with ridges and furrows
      may be more complex than in the soil of more level fields. Prior to crop
      emergence, the tracer bromide ion and the insecticide carbofuran were sprayed on
      the humic-sandy soil of a potato field with ridges and furrows. Rainfall was
      supplemented by sprinkler irrigation. The distribution of the substances in the
      soil profile of the ridges and furrows was measured on three dates in the potato
      growing season. Separate ridge and furrow systems were simulated by using the
      pesticide emission assessment at regional and local scales (PEARL) model for
      pesticide behavior in soil-plant systems. The substances travelled deeper in the
      furrow soil than in the ridge soil, because of runoff from the ridges to the
      furrows. At 19 days after application, the peak of the bromide distribution was
      measured to be in the 0.1-0.2 m layer of the ridges, while it was in the 0.3-0.5
      m layer of the furrows. After 65 days, the peak of the carbofuran distribution in
      the ridge soil was still in the 0.1 m top layer, while the pesticide was rather
      evenly distributed in the top 0.6 m of the furrow soil. The wide ranges in
      concentration measured with depth showed that preferential water flow and
      substance transport occurred in the sandy soil. Part of the bromide ion
      distribution was measured to move faster in soil than the computed wave. The
      runoff of water and pesticide from the ridges to the furrows, and the thinner
      root zone in the furrows, are expected to increase the risk of leaching to
      groundwater in ridged fields, in comparison with more level fields.

PMID- 20041325
TI  - Sorafenib plus octreotide is an effective and safe treatment in advanced
      hepatocellular carcinoma: multicenter phase II So.LAR. study.
AB  - PURPOSE: Advanced hepatocellular carcinoma (HCC) not eligible for local therapies
      has limited chances of cure. Sorafenib is a multikinase inhibitor with proven
      activity in advanced HCC. Octreotide is used in this setting with conflicting
      results. Treatment with sorafenib and long-acting octreotide was tested in
      advanced HCC to evaluate safety and activity. METHODS: Fifty patients with
      advanced HCC, Child-Pugh A or B, received sorafenib at a dosage of 800 mg/day for
      28 days with a following week of rest and long-acting octreotide at a dose of 40
      mg, administered every 28 days. RESULTS: All patients were assessable for safety
      and efficacy. Sixteen patients out of 50 (34%) were naive from other therapies,
      while all the others were previously treated with local and/or systemic
      treatments. We achieved 5 partial responses (10%), 33 stable diseases (66%) and
      12 progressions of disease (24%). Median time to progression was 7.0 months (95%
      CI, 3.0-10.9 months), and median overall survival was 12 months (95% CI, 6.3-17.4
      months). Treatment was well tolerated. Diarrhoea (6%) and hypertension (4%) were
      the most frequent grade 3 toxicities. CONCLUSIONS: Our data suggest that the
      combination between sorafenib and long-acting octreotide is active and well
      tolerated in patients with advanced HCC and could represent another efficacious
      chance for the management of this population.

PMID- 20041326
TI  - Efficacy of CR3294, a new benzamidine derivative, in the prevention of 5
      fluorouracil-induced gastrointestinal mucositis and diarrhea in mice.
AB  - PURPOSE: Gastrointestinal mucositis, commonly associated with diarrhea, is a dose
      limiting toxicity of chemotherapy. The new benzamidine derivative CR3294 reduces
      tissue damage in animal models of intestinal inflammation. Thus, we tested
      whether CR3294 had the potential to prevent chemotherapy-induced mucositis.
      METHODS: In tests on isolated cells, reactive oxygen species (ROS) formation and
      cytokine release were measured by chemiluminescence and immunoassays,
      respectively. In studies in vivo, BDF1 mice were given oral CR3294 (2.5-20 mg/kg)
      for 3 days before receiving 5-fluorouracil. Intestinal crypt survival, cell
      apoptosis and proliferation, and diarrhea score were assessed. Additionally, nude
      mice bearing tumor xenografts were treated with CR3294 and/or 5-fluorouracil, and
      tumor growth was monitored. RESULTS: CR3294 significantly inhibited cytokine
      release from stimulated leukocytes at concentrations similar to the IC(50) (2.9
      +/- 0.2 muM) for ROS production by these cells. Consistent with these molecular
      findings, CR3294 dose-dependently protected the intestinal mucosa against 5
      fluorouracil-induced toxicity in a mouse model of mucositis. The number of
      surviving crypts per cross-section in mice receiving 20 mg/kg CR3294 was 2.8-fold
      that in vehicle-treated animals (18.1 +/- 1.9 vs. 6.5 +/- 0.9, P < 0.001).
      Moreover, CR3294 decreased the cumulative diarrhea score by 50%, reduced by
      nearly 70% the incidence of severe episodes, and increased by 3-fold the number
      of mice without diarrhea. CR3294 neither affected the growth of tumor xenografts
      nor protected tumors from the cytotoxic activity of 5-fluorouracil. CONCLUSIONS:
      This study demonstrates that CR3294 acts on key molecular targets to reduce the
      signs of mucositis and the occurrence of diarrhea in mice exposed to the
      chemotherapy drug 5-fluorouracil.

PMID- 20041327
TI  - PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon
      adenocarcinoma-derived cell line.
AB  - PURPOSE: The development of multidrug resistance (MDR) is one of the major
      limitations in the treatment of cancer. Induction of P-glycoprotein (Pgp) has
      been regarded as one of the main mechanisms underlying anticancer drug-induced
      MDR. Since the induction of Pgp is (in part) regulated by the pregnane X receptor
      (PXR), the ability of several widely used anticancer drugs to activate PXR
      mediated Pgp induction was investigated. METHODS: A Pgp-reporter gene assay was
      employed to determine the ability of a panel of widely used anticancer drugs to
      induce Pgp. To further assess whether PXR could be involved in the induction of
      Pgp by anticancer drugs, Pgp protein expression after treatment with the
      anticancer drugs was determined in both wild-type and PXR-knocked down LS180
      cells. Furthermore, the effect of the anticancer drugs on the intracellular
      accumulation of the Pgp-probes rhodamine 123 and doxorubicin was determined.
      RESULTS: Our study showed that vincristine, tamoxifen, vinblastine, docetaxel,
      cyclophosphamide, flutamide, ifosfamide and paclitaxel activate PXR-mediated Pgp
      induction, and were additionally shown to affect the intracellular accumulation
      of the Pgp probe rhodamine 123. Moreover, PXR activation was also shown to reduce
      the cytotoxic activity of the Pgp substrate doxorubicin in colon cancer cells.
      CONCLUSION: Our results indicate that several anticancer drugs can activate PXR
      mediated induction of Pgp and affect the accumulation of Pgp substrates.

PMID- 20041328
TI  - Phase II study of S-1, docetaxel and cisplatin combination chemotherapy in
      patients with unresectable metastatic gastric cancer.
AB  - PURPOSE: We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1
      (DCS) combination chemotherapy in patients with unresectable metastatic gastric
      cancer. METHODS: Patients with histologically proven, unresectable metastatic
      gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy
      were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and
      intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3
      weeks. RESULTS: Thirty-four patients were enrolled between March 2005 and April
      2007. Three patients were considered ineligible and did not receive the DSC
      therapy. Clinical characteristics were as follows: median age, 63 years (range,
      44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well
      differentiated/undifferentiated adenocarcinoma, 10/21. The objective response
      rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%)
      in 31 assessable patients. Four had stable disease (12.9%) but none had
      progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7
      (22.6%) underwent curative surgery. The median survival time and progression-free
      survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days
      (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity
      was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included
      anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved,
      and no toxic deaths were observed. CONCLUSIONS: DCS combination chemotherapy is
      highly active against unresectable metastatic gastric cancer and can be given
      safely with proper management of adverse events. Further studies of this
      combination are warranted.

PMID- 20041329
TI  - Severe aortic regurgitation after percutaneous transcatheter aortic valve
      implantation: on the importance to clarify the underlying pathophysiology.
AB  - Severe symptomatic aortic stenosis in a 90-year-old man was treated with
      percutaneous aortic valve implantation (TAVI) with a 29-mm CoreValve Revalving
      system. Following implantation, severe aortic regurgitation occurred.
      Echocardiography showed a small paravalvular and a huge valvular leakage,
      probably due to one malfunctioning valve leaflet. Concerning this
      pathophysiology, a further TAVI was performed using a second 29-mm CoreValve
      Revalving system, as a "valve-in-valve" implantation.

PMID- 20041330
TI  - Effects of atypical (risperidone) and typical (haloperidol) antipsychotic agents
      on astroglial functions.
AB  - Although classical and atypical antipsychotics may have different neurotoxic
      effects, their underlying mechanisms remain to be elucidated, especially
      regarding neuroglial function. In the present study, we compared the atypical
      antipsychotic risperidone (0.01-10 MUM) with the typical antipsychotic
      haloperidol (0.01-10 MUM) regarding different aspects such as glutamate uptake,
      glutamine synthetase (GS) activity, glutathione (GSH) content, and intracellular
      reactive oxygen species (ROS) production in C6 astroglial cells. Risperidone
      significantly increased glutamate uptake (up to 27%), GS activity (14%), and GSH
      content (up to 17%). In contrast, haloperidol was not able to change any of these
      glial functions. However, at concentration of 10 MUM, haloperidol increased (12%)
      ROS production. Our data contribute to the clarification of different hypothesis
      concerning the putative neural responses after stimulus with different
      antipsychotics, and may establish important insights about how brain rewiring
      could be enhanced.

PMID- 20041331
TI  - Vestibular dysfunction in migraine: effects of associated vertigo and motion
      sickness.
AB  - The mechanisms of vestibular migraine and motion sickness remain unknown. The
      aims of this study were to determine interictal vestibular dysfunction in
      migraineurs according to associated dizziness/vertigo and motion sickness, and to
      find out whether impaired uvulonodular inhibition over the vestibular system
      underlies the vestibular symptoms and signs by measuring tilt suppression of the
      vestibulo-ocular reflex (VOR). One hundred and thirty-one patients with migraine
      [65 with vestibular migraine (MV), 41 with migrainous dizziness (MD), and 25 with
      migraine only (MO)] and 50 normal controls underwent evaluation of vestibular
      function. Motion sickness was assessed using the motion sickness susceptibility
      questionnaire (MSSQ) and subjective scale. Compared with normal controls and MO
      group, patients with MV/MD showed increased VOR time constant (TC) and greater
      suppression of the post-rotatory nystagmus with forward head tilt. The mean MSSQ
      score and subjective scale were highest in MV group, followed by MD, MO, and
      controls (p = 0.002, p < 0.001). Multiple linear regression model analyses
      revealed that motion sickness is an independent factor of TC prolongation (p =
      0.024). Twenty-eight (21.4%) patients with migraine also showed perverted head
      shaking nystagmus and 12 (9.2%) had positional nystagmus. In view of the
      increased tilt suppression of the VOR, we speculate that dysfunction of the
      nodulus/uvula may not account for the prolonged TCs in MD/MV. Instead, innate
      hypersensitivity of the vestibular system may be an underlying mechanism of
      motion sickness and increased TC in MD/MV. The increased tilt suppression may be
      an adaptive cerebellar mechanism to suppress the hyperactive vestibular system in
      migraineurs.

PMID- 20041332
TI  - High expression level of a foot and mouth disease virus epitope in tobacco
      transplastomic plants.
AB  - Chloroplast transformation has an extraordinary potential for antigen production
      in plants because of the capacity to accumulate high levels of recombinant
      proteins and increased biosafety due to maternal plastid inheritance in most
      crops. In this article, we evaluate tobacco chloroplasts transformation for the
      production of a highly immunogenic epitope containing amino acid residues 135-160
      of the structural protein VP1 of the foot and mouth disease virus (FMDV). To
      increase the accumulation levels, the peptide was expressed as a fusion protein
      with the beta-glucuronidase reporter gene (uidA). The recombinant protein
      represented the 51% of the total soluble proteins in mature leaves, a level
      higher than those of the Rubisco large subunit, the most abundant protein in the
      leaf of a wild-type plant. Despite this high accumulation of heterologous
      protein, the transplastomic plants and wild-type tobacco were phenotypically
      indistinguishable. The FMDV epitope expressed in transplastomic plants was
      immunogenic in mice. These results show that transplastomic tobacco express
      efficiently the recombinant protein, and we conclude that this technology allows
      the production of large quantities of immunogenic proteins.

PMID- 20041333
TI  - Inoculation of tomato plants (Solanum lycopersicum) with growth-promoting
      Bacillus subtilis retards whitefly Bemisia tabaci development.
AB  - Root inoculation of tomato (Solanum lycopersicum) plants with a Bacillus subtilis
      strain BEB-DN (BsDN) isolated from the rhizosphere of cultivated potato plants
      was able to promote growth and to generate an induced systemic resistance (ISR)
      response against virus-free Bemisia tabaci. Growth promotion was evident 3 weeks
      after inoculation. No changes in oviposition density, preference and nymphal
      number in the early stages of B. tabaci development were observed between BsDN
      treated plants and control plants inoculated with a non-growth promoting Bs
      strain (PY-79), growth medium or water. However, a long-term ISR response was
      manifested by a significantly reduced number of B. tabaci pupae developing into
      adults in BsDN-treated plants. The observed resistance response appeared to be a
      combination of jasmonic acid (JA) dependent and JA-independent responses, since
      the BsDN-related retardation effect on B. tabaci development was still effective
      in the highly susceptible spr2 tomato mutants with an impaired capacity for JA
      biosynthesis. A screening of 244 genes, 169 of which were previously obtained
      from subtractive-suppressive-hybridization libraries generated from B. tabaci
      infested plants suggested that the BsDN JA-dependent ISR depended on an anti
      nutritive effect produced by the simultaneous expression of genes coding
      principally for proteases and proteinase inhibitors, whereas the JA-independent
      ISR observed in the spr2 background curiously involved the up-regulation of
      several photosynthetic genes, key components of the phenyl-propanoid and
      terpenoid biosynthetic pathways and of the Hsp90 chaperonin, which probably
      mediated pest resistance response(s), in addition to the down-regulation of
      pathogenesis and hypersensitive response genes.

PMID- 20041334
TI  - The maize root stem cell niche: a partnership between two sister cell
      populations.
AB  - Using transcript profile analysis, we explored the nature of the stem cell niche
      in roots of maize (Zea mays). Toward assessing a role for specific genes in the
      establishment and maintenance of the niche, we perturbed the niche and
      simultaneously monitored the spatial expression patterns of genes hypothesized as
      essential. Our results allow us to quantify and localize gene activities to
      specific portions of the niche: to the quiescent center (QC) or the proximal
      meristem (PM), or to both. The data point to molecular, biochemical and
      physiological processes associated with the specification and maintenance of the
      niche, and include reduced expression of metabolism-, redox- and certain cell
      cycle-associated transcripts in the QC, enrichment of auxin-associated
      transcripts within the entire niche, controls for the state of differentiation of
      QC cells, a role for cytokinins specifically in the PM portion of the niche,
      processes (repair machinery) for maintaining DNA integrity and a role for gene
      silencing in niche stabilization. To provide additional support for the
      hypothesized roles of the above-mentioned and other transcripts in niche
      specification, we overexpressed, in Arabidopsis, homologs of representative genes
      (eight) identified as highly enriched or reduced in the maize root QC. We
      conclude that the coordinated changes in expression of auxin-, redox-, cell cycle
      and metabolism-associated genes suggest the linkage of gene networks at the
      level of transcription, thereby providing additional insights into events likely
      associated with root stem cell niche establishment and maintenance.

PMID- 20041335
TI  - Expression of metalloproteases and their inhibitors in primary tumors and in
      local recurrences after mastectomy for breast cancer.
AB  - AIMS: To investigate the expression of matrix metalloproteases (MMPs) and their
      inhibitors (TIMPs) in patients who develop local recurrence (LR) after
      mastectomy. METHODS: We analyzed the expressions of MMP-1, -2, -7, -9, -11, -13, 
      14, TIMP-1, -2, and -3, using immunohistochemical techniques, in primary tumors
      from patients without tumoral recurrence (n = 50), patients who developed distant
      metastasis (n = 50), and from patients who develop LRs (n = 25). LRs of the
      latter group were also analyzed for MMPs expression. All the patients underwent
      mastectomy. RESULTS: Score values for all MMPs and TIMPs were significantly
      higher in primary tumors of patients with distant metastasis. Primary tumors from
      patients with LR have lower expressions of MMPs and TIMPs compared with those
      from patients who developed distant metastasis, and with patients without
      recurrence for some MMPs. Remarkably, however, primary tumors from patients with
      LR showed significantly higher percentage of TIMP-1 and 2 expression in stromal
      cells compared to primary tumors from patients with distant metastasis or primary
      tumors from patients without tumoral progression. Furthermore, LRs had
      significantly higher MMP-9 expression than their corresponding primary tumors.
      CONCLUSIONS: Our data indicate differences in MMPs/TIMPs expression between
      primary tumors of patients with LRs and of those with distant metastasis, both
      after mastectomy for breast cancer.

PMID- 20041337
TI  - Externalizing behaviors in preadolescents: familial risk to externalizing
      behaviors and perceived parenting styles.
AB  - The aim was to investigate the contribution of familial risk to externalizing
      behaviors (FR-EXT), perceived parenting styles, and their interactions to the
      prediction of externalizing behaviors in preadolescents. Participants were
      preadolescents aged 10-12 years who participated in TRAILS, a large prospective
      population-based cohort study in the Netherlands (N = 2,230). Regression analyses
      were used to determine the relative contribution of FR-EXT and perceived
      parenting styles to parent and teacher ratings of externalizing behaviors. FR-EXT
      was based on lifetime parental externalizing psychopathology and the different
      parenting styles (emotional warmth, rejection, and overprotection) were based on
      the child's perspective. We also investigated whether different dimensions of
      perceived parenting styles had different effects on subdomains of externalizing
      behavior. We found main effects for FR-EXT (vs. no FR-EXT), emotional warmth,
      rejection, and overprotection that were fairly consistent across rater and
      outcome measures. More specific, emotional warmth was the most consistent
      predictor of all outcome measures, and rejection was a stronger predictor of
      aggression and delinquency than of inattention. Interaction effects were found
      for FR-EXT and perceived parental rejection and overprotection; other
      interactions between FR-EXT and parenting styles were not significant.
      Correlations between FR-EXT and perceived parenting styles were absent or very
      low and were without clinical significance. Predominantly main effects of FR-EXT
      and perceived parenting styles independently contribute to externalizing
      behaviors in preadolescents, suggesting FR-EXT and parenting styles to be two
      separate areas of causality. The relative lack of gene-environment interactions
      may be due to the epidemiological nature of the study, the preadolescent age of
      the subjects, the measurement level of parenting and the measurement level of FR
      EXT, which might be a consequence of both genetic and environmental factors.

PMID- 20041336
TI  - Effects of season on sleep and skin temperature in the elderly.
AB  - The effects of season on sleep and skin temperature (Tsk) in 19 healthy, elderly
      volunteers were investigated. Measurements were obtained in summer, winter, and
      fall, and activity levels were monitored using a wrist actigraph system for five
      consecutive days. The temperature and humidity of the bedrooms of the subjects'
      homes were measured continuously for five days. During actigraphic measurement,
      Tsk during sleep was measured for two nights. The bedroom temperature and
      humidity significantly increased in summer compared to winter and fall. In
      summer, the total sleep time decreased (mean +/- SE min; summer, 350.8 +/- 15.7;
      winter, 426.5 +/- 14.2; fall, 403.2 +/- 16.4) and wakefulness increased (P <
      0.003) compared to those in fall or winter. The sleep efficiency index that was
      derived from wrist actigraphy was significantly decreased (P < 0.001) in summer
      (81.4 +/- 2.9%) compared with winter (91.6 +/- 1.3%) or fall (90.2 +/- 1.2%). The
      forehead Tsk significantly increased, while the chest and thigh Tsks were
      decreased in summer compared to those in fall or winter. These results suggest
      that, in the elderly, sleep is disturbed in summer more than in other seasons,
      and that this disturbance is related to fluctuations in Tsk.

PMID- 20041338
TI  - Patterns of gene expression in a scleractinian coral undergoing natural
      bleaching.
AB  - Coral bleaching is a major threat to coral reefs worldwide and is predicted to
      intensify with increasing global temperature. This study represents the first
      investigation of gene expression in an Indo-Pacific coral species undergoing
      natural bleaching which involved the loss of algal symbionts. Quantitative real
      time polymerase chain reaction experiments were conducted to select and evaluate
      coral internal control genes (ICGs), and to investigate selected coral genes of
      interest (GOIs) for changes in gene expression in nine colonies of the
      scleractinian coral Acropora millepora undergoing bleaching at Magnetic Island,
      Great Barrier Reef, Australia. Among the six ICGs tested, glyceraldehyde 3
      phosphate dehydrogenase and the ribosomal protein genes S7 and L9 exhibited the
      most constant expression levels between samples from healthy-looking colonies and
      samples from the same colonies when severely bleached a year later. These ICGs
      were therefore utilised for normalisation of expression data for seven selected
      GOIs. Of the seven GOIs, homologues of catalase, C-type lectin and chromoprotein
      genes were significantly up-regulated as a result of bleaching by factors of
      1.81, 1.46 and 1.61 (linear mixed models analysis of variance, P < 0.05),
      respectively. We present these genes as potential coral bleaching response genes.
      In contrast, three genes, including one putative ICG, showed highly variable
      levels of expression between coral colonies. Potential variation in microhabitat,
      gene function unrelated to the stress response and individualised stress
      responses may influence such differences between colonies and need to be better
      understood when designing and interpreting future studies of gene expression in
      natural coral populations.

PMID- 20041339
TI  - A phase I study of S-1 treatment with a 3 week schedule in advanced biliary
      cancer patients with or without hepatic dysfunction.
AB  - PURPOSE: A 3 week treatment schedule consisting of 2 weeks of S-1 therapy and 1
      week of no therapy was introduced to reduce the toxicity and increase the
      convenience of combination chemotherapy. Hepatic dysfunction (HD) is common in
      patients with biliary tract cancer. A phase I study was conducted to assess the
      effects of a 3 week treatment schedule in Asian patients with or without HD.
      METHODS: Forty-six patients were stratified into four groups, according to the HD
      criteria of the National Cancer Institute Organ Dysfunction Working Group. A
      three dose escalation schema was used. RESULTS: In the normal hepatic function
      group, two dose-limiting toxicity (DLT) events occurred among 12 patients at the
      prespecified maximal dose of 100 mg/m2/day. This dose was thereby established as
      the maximal tolerable dose (MTD). No DLT events were observed at the predefined
      maximal dose of 80 mg/m2/day in the mild HD group. In the moderate HD group, two
      DLT events occurred among five patients treated with 80 mg/m2/day, and the MTD
      was defined as 70 mg/m2/day. Two of six subjects in the severe HD group
      experienced DLT events at doses of 60 mg/m2/day and none developed DLT events at
      50 mg/m2/day. CONCLUSIONS: The MTDs for a 3 week schedule of S-1 treatment were
      defined in patients with or without hepatic dysfunction. A 3 week treatment
      regimen of S-1 might be a platform for combination with newer cytotoxic agents or
      biologics.

PMID- 20041340
TI  - Sphingosine-1-phosphate: a potential therapeutic agent against human breast
      cancer.
AB  - Sphingosine-1-phosphate (S1P) is an important regulator of cancer development and
      progression. Its cellular concentration is controlled predominantly by
      sphingosine kinase (SK) and sphingosine-1-phosphate lyase (SPL). In the current
      study we showed that mRNA expressions for both SK and SPL were up-regulated
      throughout all four disease stages in human breast cancer patients. Exogenous
      administration of S1P produced a bell-shaped dose response for apoptosis in
      normal mammary gland MCF12A cells but a sigmoid-shaped apoptotic response in
      breast cancer MCF7 cells. Co-administration of S1P enhanced the cytotoxicity of
      anticancer drug docetaxel against MCF7 cells.

PMID- 20041341
TI  - Isolation of a novel gene encoding a 3,5,6-trichloro-2-pyridinol degrading enzyme
      from a cow rumen metagenomic library.
AB  - 3,5,6-trichloro-2-pyridinol (TCP) is a major metabolite of the insecticide
      chlorpyrifos and is hazardous to human and animal health. A gene encoding a TCP
      degrading enzyme was cloned from a metagenomic library prepared from cow rumen.
      The gene (tcp3A) is 2.5 kb in length, encoding a protein (Tcp3A) of 599 amino
      acid residues. Tcp3A has a potential signal sequence, as well as a putative
      ATP/GTP binding site, and a likely amidation site. The molecular weight of the
      enzyme is 62 kDa by SDS-PAGE. Comparison of Tcp3A with the NCBI database using
      BLASTP revealed homology to amidohydrolase proteins. Recombinant Escherichia coli
      harboring the tcp3A gene could utilize TCP as the sole source of carbon. TLC and
      HPLC revealed that TCP was degraded by recombinant E. coli harboring tcp3A. This
      is the first report of a gene encoding a TCP degrading enzyme.

PMID- 20041342
TI  - A framework for measurement feedback to improve decision-making in mental health.
AB  - The authors present a multi-level framework for conceptualizing and designing
      measurement systems to improve decision-making in the treatment and prevention of
      child and adolescent mental health problems as well as the promotion of well
      being. Also included is a description of the recommended drivers of the
      development and refinement of these measurement systems and the importance of the
      architecture upon which these measurement systems are built. The authors conclude
      with a set of recommendations for the next steps for the field.

PMID- 20041343
TI  - Bioavailable phosphorus transport from a hillslope cropland of purple soil under
      natural and simulated rainfall.
AB  - To further understand the mechanism of bioavailable total P (BAP) and
      bioavailable dissolved P (BDP) transport by overland and subsurface flow, we
      exposed a runoff plot 4.5 m long * 1.5 m wide * 0.6 m deep to simulated and
      natural rainfall in order to study the effects of rainfall type, rainfall
      intensity, and vegetation cover on BAP and BDP transport. The results showed that
      vegetation cover could alleviate the discharge of overland flow and sediment
      transport and enhance subsurface flow. BAP transport significantly increased with
      elevated rainfall intensity. Vegetation cover reduced the BAP transport by
      overland flow and increased it by subsurface flow. BDP transport showed no
      significant relationship with vegetation cover and rainfall type. The
      bioavailable particulate P (BPP) transport by overland flow contributed to no
      less than 90% by weight of total BAP, and the BPP transport by subsurface flow
      contributed to no less than 60% by weight of total BAP. Short-time heavy rainfall
      caused more BAP transport and accelerated non-point source pollution.

PMID- 20041344
TI  - Environmental repercussions of cane-sugar industries on the Chhoti Gandak river
      basin, Ganga Plain, India.
AB  - Chhoti Gandak river basin, situated in the Ganga Plain, is one of India's most
      productive cane-sugar industrial belts. Soil and groundwater samples were
      collected to investigate the impacts of these industries on the environment of
      the Chhoti Gandak river basin with special reference to soil and water. The
      results show that concentration of most metals are affected by industrial
      activities and surrounding agricultural practices. It is evidenced by increased
      heavy metal concentration in the soils as well as in the aquifers. Metals such as
      Pb, Cu, and Zn in the soil around the industrial sets are found significantly
      higher than their normal values in the soil. Metals like Fe and Mn in the
      groundwater are more than the permissible limit prescribed by the World Health
      Organization. In this study, an attempt was made to distinguish between the
      naturally occurring and anthropogenically induced metals in the soil. Analysis of
      geochemical properties, disposal of industrial wastes, inadequate application of
      agrochemicals, and their impact on environment indicate the sustainable
      implementation of integrated wastewater management plan in these industrial sets
      and also in similar situations.

PMID- 20041346
TI  - Assessment of effects of climate change and grazing activity on grassland yield
      in the Three Rivers Headwaters Region of Qinghai-Tibet Plateau, China.
AB  - Inter-annual dynamics of grassland yield of the Three Rivers Headwaters Region of
      Qinghai-Tibet Plateau of China in 1988-2005 was analyzed using the GLO-PEM model,
      and the herbage supply function was evaluated. The results indicate that while
      grassland yield in the region showed marked inter-annual fluctuation there was a
      trend of increased yield over the 18 years of the study. This increase was
      especially marked for Alpine Desert and Alpine Steppe and in the west of the
      region. The inter-annual coefficient of variation of productivity increased from
      the east to the west of the region and from Marsh, Alpine Meadow, Alpine Steppe,
      Temperate Steppe to Alpine Desert grasslands. Climate change, particularly
      increased temperatures in the region during the study period, is suggested to be
      the main cause of increased grassland yield. However, reduced grazing pressure
      and changes to the seasonal pattern of grazing could also have influenced the
      grassland yield trend. These findings indicate the importance of understanding
      the function of the grassland ecosystems in the region and the effect of climate
      change on them especially in regard to their use to supply forage for animal
      production. Reduction of grazing pressure, especially during winter, is indicated
      to be critical for the restoration and sustainable use of grassland ecosystems in
      the region.

PMID- 20041345
TI  - Biomagnifications of mercury and methylmercury in tuna and mackerel.
AB  - Seawater may be contaminated by harmful substances, including toxic elements
      released by human activities. The present study evaluates the total mercury and
      methylmercury concentrations and their correlations to fish body size in longtail
      tuna and short-bodied mackerel from Chendring, Kuantan, at east coast and Kuala
      Perlis at west costs of Peninsular Malaysia during May to November 2007. Total
      mercury and methylmercury in muscle tissue of 69 samples of longtail tuna and
      short-bodied mackerel, ranged from 0.180 to 1.460 MUg/g and 0.0.169-0.973 MUg/g
      and 0.251-1.470 MUg/g and 0.202-1.352, whereas the methylmercury to total mercury
      ratio ranged from 70% to 83%, respectively. Samples of both species from the east
      coast showed higher levels of mercury compared to those from west coast. In all
      of the locations, significant positive correlations were found between fish body
      weight and mercury content (R(2) > 0.470). The estimated weekly intake of total
      mercury and methylmercury from the consumption 66.33 g/week of short-bodied
      mackerel and 18.34 g/week of longtail tuna (based on local dietry survey) was
      found to be lower than the maximum limit of 5 and 1.5 MUg/kg bodyweight
      established by FAO/WHO and codex, respectively.

PMID- 20041347
TI  - Sarcoptic mange infestation in pigs in a hilly region of Meghalaya.
AB  - Skin lesions were collected from 15 adult crossbred pigs maintained at the pig
      farm of ICAR Research Complex for the North-Eastern Hill Region, Umiam, a hilly
      region of the state of Meghalaya, India. Skin scrapings of these 15 animals were
      examined by KOH digestion method. Presence of mites were detected in five animals
      which were indistinguishable from Sarcoptes scabiei var. suis. Infected pigs were
      treated with a single dose of Ivermectin at 200 ug/kg body weight,
      subcutaneously. No mites were recovered from treated pigs after a period of 10
      days of post-treatment. The presence of S. scabiei var. suis in pigs from this
      part of the country has never been reported. This infestation has great
      significance because it affects the growth rate and feed conversion
      significantly, specially to the grower and weaned pigs. It can be concluded that
      S. scabiei var. suis infestation is prevalent in hilly region of Meghalaya. The
      pig producers are generally unaware about the severity of the problem of mite
      infestation, so precaution should be taken to prevent their valuable pigs from S.
      scabiei var. suis infestation.

PMID- 20041348
TI  - Completed suicide and marital status according to the Italian region of origin.
AB  - Completed suicide is associated with marital status; being unmarried is
      associated with a higher suicide rate as compared with being married or living
      with a partner. Moreover, the region of origin may be particularly important when
      trying to explain major inequalities in suicide rates across a country. Data were
      obtained from the Italian Database on Mortality, collected by the Italian Census
      Bureau (ISTAT) and processed by the Italian National Institute of Health
      Statistics Unit. The Italian population in the last Italian census (October 2001)
      was used to estimate age-standardized mortality rates from suicide by marital
      status (ICD-9 revision: E950-959) and "natural" causes (ICD-9 revision: 0-280;
      320-799). Rate Ratios and 95% confidence intervals were calculated using married
      individuals as a reference. All analyses were conducted separately for men and
      women for 2000-2002, the most recent years with data available. Logistic
      regression analysis was used to compare differences by marital status for suicide
      versus death from natural causes. There are major inequalities in suicide rates
      in Italy. The North region has the highest suicide rates both for married and non
      married individuals. Sardinia Island has the highest male suicide rate in Italy
      23.07 per 100,000 per year-compared with the average national male suicide rate
      of 13.80, a difference which is significantly higher by 67% (RR: 1.67; 95%CI =
      1.40-1.99). In contrast, Sardinia has one of the lowest female suicide rates
      among the Italian regions, close to that of the South and the Center regions. The
      North-East is the only region where the suicide rate among divorced men is
      significantly higher than that of married men. In the South, widowers have the
      highest suicide rate, with a rate 6-times that of married men (RR = 5.66; 95%CI =
      4.46-7.18). Major inequalities in suicide rates by region may derive from
      different socio-cultural backgrounds, confirming the notion that suicide is a
      multifaceted phenomenon. The results of the present study indicate that suicide
      prevention must take into account the social and cultural characteristics of
      different communities. Moreover, these findings support the notion that marital
      status may play a central role in influencing suicide.

PMID- 20041349
TI  - Glass-composite prototyping for flow PCR with in situ DNA analysis.
AB  - In this article, low cost microfluidic devices have been used for simultaneous
      amplification and analysis of DNA. Temperature gradient flow PCR was performed,
      during which the unique fluorescence signature of the amplifying product was
      determined. The devices were fabricated using xurography, a fast and highly
      flexible prototype manufacturing method. Each complete iterative design cycle,
      from concept to prototype, was completed in less than 1 h. The resulting devices
      were of a 96% glass composition, thereby possessing a high thermal stability
      during continuous-flow PCR. Volumetric flow rates up to 4 microl/min induced no
      measurable change in the temperature distribution within the microchannel. By
      incorporating a preliminary channel passivation protocol, even the first
      microliters through the system exhibited a high amplification efficiency, thereby
      demonstrating the biocompatibility of this fabrication technique for DNA
      amplification microfluidics. The serpentine microchannel induced 23 temperature
      gradient cycles in 15 min at a 2 microl/min flow rate. Fluorescent images of the
      device were acquired while and/or after the PCR mixture filled the microchannel.
      Because of the relatively high initial concentration of the phage DNA template
      (PhiX174), images taken after 10 min (less than 15 PCR cycles) could be used to
      positively identify the PCR product. A single fluorescent image of a full device
      provided the amplification curve for the entire reaction as well as multiple high
      resolution melting curves of the amplifying sample. In addition, the signal-to
      noise ratio associated with the spatial fluorescence was characterized as a
      function of spatial redundancy and acquisition time.

PMID- 20041350
TI  - EMAP II-based antiangiogenic-antiendothelial in vivo combination therapy of
      pancreatic cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) frequently resists
      conventional cytotoxic therapy. The antitumor effects of endothelial monocyte
      activating polypeptide II (EMAP) have been attributed to its antiendothelial and
      antiangiogenic activities. We tested the hypothesis that a combination of EMAP
      with bevacizumab (Bev) and gemcitabine (Gem) targets different pathways of PDAC
      progression and represents more effective treatment. METHODS: Proliferation of
      PDAC and endothelial cell lines was evaluated in vitro. In vivo tumor growth and
      survival PDAC xenograft experiments were performed with EMAP, Bev, and Gem,
      either alone or in combination. Intratumoral microvessel density and
      proliferative activity were analyzed by immunostaining with PECAM-1 and
      proliferating cell nuclear antigen antibodies, and apoptotic activity was
      measured by the TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end
      labeling) procedure. RESULTS: Compared with controls, net reduction in tumor
      growth in EMAP, Bev, Gem, EMAP + Bev, EMAP + Gem, Bev + Gem, and EMAP + Bev + Gem
      groups was 58, 40, 40, 67, 68, 69, and 96%, respectively. Addition of EMAP to the
      Bev + Gem group statistically significantly improved survival at a median of >8
      days while inducing long-term survival in some animals after maintenance therapy.
      Combination treatment of EMAP with Bev and Gem reduced proliferation of
      endothelial but not of PDAC cells. Addition of EMAP to Bev and Gem statistically
      significantly decreased proliferative activity while maintaining a comparable
      rate of microvessel density and apoptosis. CONCLUSIONS: Addition of
      antiendothelial EMAP to a Bev and Gem regimen improves antitumor effects in a
      xenograft model of PDAC. This multitargeting strategy to prevent PDAC progression
      shows therapeutic promise and may overcome limitations by combinations of Gem
      with anti-vascular endothelial growth factor agents alone.

PMID- 20041351
TI  - Management of recurrent rectal cancer.
AB  - BACKGROUND: Here we present a concise review on the evaluation and management of
      locally recurrent rectal cancer, which despite marked reductions in the rate of
      recurrent rectal cancer remains an important problem. METHODS: This educational
      review discusses the diagnosis, evaluation, and management of recurrent rectal
      cancer. RESULTS: Despite improvements in both the neoadjuvant and surgical
      management of rectal cancer, local recurrence is still an important problem, with
      documented recurrence rates of 4% to 8%. The local management of recurrence
      requires a team of specialist. Accurate detection and diagnosis followed by
      chemoradiotherapy and surgical resection may result in 5-year survival rates of
      up to 35%. CONCLUSIONS: We discuss the diagnosis, evaluation, and management of
      locally recurrent rectal cancer. Locally recurrent rectal cancer can be
      successfully managed with multimodal therapy leading to successful palliation and
      often cure.

PMID- 20041352
TI  - On the robustness of the geometrical model for cell wall deposition.
AB  - All plant cells are provided with the necessary rigidity to withstand the turgor
      by an exterior cell wall. This wall is composed of long crystalline cellulose
      microfibrils embedded in a matrix of other polysaccharides. The cellulose
      microfibrils are deposited by mobile membrane bound protein complexes in
      remarkably ordered lamellar textures. The mechanism by which these ordered
      textures arise, however, is still under debate. The geometrical model for cell
      wall deposition proposed by Emons and Mulder (Proc. Natl. Acad. Sci. 95, 7215
      7219, 1998) provides a detailed approach to the case of cell wall deposition in
      non-growing cells, where there is no evidence for the direct influence of other
      cellular components such as microtubules. The model successfully reproduces even
      the so-called helicoidal wall; the most intricate texture observed. However, a
      number of simplifying assumptions were made in the original calculations. The
      present work addresses the issue of the robustness of the model to relaxation of
      these assumptions, by considering whether the helicoidal solutions survive when
      three aspects of the model are varied. These are: (i) the shape of the insertion
      domain, (ii) the distribution of lifetimes of individual CSCs, and (iii)
      fluctuations and overcrowding. Although details of the solutions do change, we
      find that in all cases the overall character of the helicoidal solutions is
      preserved.

PMID- 20041353
TI  - Multistability in a model for CTL response to HTLV-I infection and its
      implications to HAM/TSP development and prevention.
AB  - Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is a retrovirus that has
      been identified as the causative agent of HTLV-I-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) and other illnesses. HTLV-I infects primarily
      CD4(+) T cells and the transmission occurs through direct cell-to-cell contact.
      HAM/TSP patients harbor higher proviral loads in peripheral blood lymphocytes
      than asymptomatic carriers. Also, HAM/TSP patients exhibit a remarkably high
      number of circulating HTLV-I-specific CD8(+) cytotoxic T lymphocytes (CTLs) in
      the peripheral blood. While CTLs have a protective role by killing the infected
      cells and lowering the proviral load, a high level of CTLs and their cytotoxicity
      are believed to be a main cause of the development of HAM/TSP. A mathematical
      model for HTLV-I infection of CD4(+) T cells that incorporates the CD8(+)
      cytotoxic T-cell (CTL) response is investigated. Our mathematical analysis
      reveals that the system can stabilize at a carrier steady-state with persistent
      viral infection but no CTL response, or at a HAM/TSP steady-state at which both
      the viral infection and CTL response are persistent. We also establish two
      threshold parameters R(0) and R(1), the basic reproduction numbers for viral
      persistence and for CTL response, respectively. We show that the parameter R(1)
      can be used to distinguish asymptomatic carriers from HAM/TSP patients, and as an
      important control parameter for preventing the development of HAM/TSP.

PMID- 20041354
TI  - A multicompartment liver-based pharmacokinetic model for benzene and its
      metabolites in mice.
AB  - Benzene is a highly flammable, colorless liquid. Ubiquitous exposures result from
      its presence in gasoline vapors, cigarette smoke, and industrial processes. After
      uptake into the body, benzene undergoes a series of metabolic transformations to
      multiple metabolites that exert toxic effects on the bone marrow. We developed a
      physiologically based pharmacokinetic model for the uptake and elimination of
      benzene in mice to relate the concentration of inhaled and orally administered
      benzene to the tissue doses of benzene and its key metabolites. This model takes
      into account the zonal distribution of enzymes and metabolism in the liver rather
      than treating the liver as one homogeneous compartment, and considers metabolism
      in tissues other than the liver. Analysis was done to examine the existence and
      uniqueness of solutions of the system. We then formulated an inverse problem to
      obtain estimates for the unknown parameters; data from multiple laboratories and
      experiments were used. Despite the sources of variability, the model simulations
      matched the data reasonably well in most cases. Our study shows that the
      multicompartment metabolism model does improve predictions over the previous
      model (Cole et al. in J. Toxicol. Environ. Health, 439-465, 2001) and that in
      vitro metabolic constants can be successfully extrapolated to predict in vivo
      data for benzene metabolism and dosimetry.

PMID- 20041355
TI  - A rapid-mutation approximation for cell population dynamics.
AB  - Carcinogenesis and cancer progression are often modeled using population dynamics
      equations for a diverse somatic cell population undergoing mutations or other
      alterations that alter the fitness of a cell and its progeny. Usually it is then
      assumed, paralleling standard mathematical approaches to evolution, that such
      alterations are slow compared to selection, i.e., compared to subpopulation
      frequency changes induced by unequal subpopulation proliferation rates. However,
      the alterations can be rapid in some cases. For example, results in our lab on in
      vitro analogues of transformation and progression in carcinogenesis suggest there
      could be periods where rapid alterations triggered by horizontal intercellular
      transfer of genetic material occur and quickly result in marked changes of cell
      population structure.We here initiate a mathematical study of situations where
      alterations are rapid compared to selection. A classic selection-mutation
      formalism is generalized to obtain a "proliferation-alteration" system of
      ordinary differential equations, which we analyze using a rapid-alteration
      approximation. A system-theoretical estimate of the total-population net growth
      rate emerges. This rate characterizes the diverse, interacting cell population
      acting as a single system; it is a weighted average of subpopulation rates, the
      weights being components of the Perron-Frobenius eigenvector for an ergodic
      Markov-process matrix that describes alterations by themselves. We give a
      detailed numerical example to illustrate the rapid-alteration approximation,
      suggest a possible interpretation of the fact that average aneuploidy during
      cancer progression often appears to be comparatively stable in time, and briefly
      discuss possible generalizations as well as weaknesses of our approach.

PMID- 20041356
TI  - Regional anesthesia and prostate cancer recurrence.

PMID- 20041357
TI  - Transjugular intrahepatic portosystemic shunt related paradoxical air embolism
      during orthotopic liver transplantation.

PMID- 20041358
TI  - Anesthesiologists' learning curves for ultrasound assessment of the lumbar spine.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound assessment of the lumbar spine to
      facilitate neuraxial anesthesia has recently received much attention. The
      transfer of knowledge pertaining to this skill has never been studied. The
      purpose of this study was to determine the amount of teaching needed to achieve
      competence in spinal ultrasound. METHODS: Participants were given reading
      material and a link to a video presentation on spinal ultrasound. As well, they
      attended a 45-min lecture followed by a 30-min hands-on workshop. They were then
      assessed individually 1-2 weeks later. The assessment was performed on a live
      model using a low frequency curved ultrasound probe (2-5 mHz). Participants were
      asked to determine, at random lumbar spinal levels, the optimal insertion point
      and the depth to the ligamentum flavum-dura mater unit (up to 20 trials, 2 min
      per trial). Feedback was provided by an expert for each incorrect task. The
      learning curves were constructed, using the cumulative sum method, by comparing
      the participants' results with those of a benchmark established by experts.
      Statistical analysis was performed using STATA 9.2 for Macintosh (College
      Station, TX, USA). RESULTS: A total of 308 anesthesiologists were approached and
      18 anesthesiologists participated in the study. Only five of the 18 participants
      (27%) achieved competence in determining the interspace, with a median number of
      11 attempts (range 8-18). None of the participants achieved competence in
      determining either the insertion point or the depth to the ligamentum flavum-dura
      mater unit. CONCLUSIONS: Under the study conditions, 20 supervised trials plus
      teaching sessions were not enough for the participants to achieve competence in
      different aspects of ultrasound assessment of the lumbar spine. These results may
      well be considered when planning teaching sessions and workshops in the future.

PMID- 20041359
TI  - Effect of gender and type 2 diabetes mellitus on heart rate recovery in patients
      with coronary artery disease after cardiac rehabilitation.
AB  - INTRODUCTION: The purpose of this study was to clarify whether type 2 diabetic
      patients with coronary disease are subject to similar benefits in heart rate
      recovery (HRR) as non-diabetic counterpatrs after cardiac rehabilitation,
      assessing men and women subjects separately. MATERIAL AND METHODS: The data used
      for this analysis were from an eight-week, phase-II cardiac rehabilitation
      including 284 patients with ischaemic heart disease who were managed at Tehran
      Heart Centre between July 2004 and January 2006. The heart rate parameters were
      compared between diabetic and non-diabetic patients before and after cardiac
      rehabilitation. Diabetic and non-diabetic patients had similar age and left
      ventricular ejection fraction. RESULTS: Among men, the non-diabetic patients
      achieved a greater improvement in peak heart rate and heart rate recovery (HRR).
      Additionally, lower resting heart rate was found in nondiabetic men after
      rehabilitation. In the women >or= 50 years old, there was no significant
      difference between diabetic and non-diabetic. The non-diabetic women < 50 years
      old showed significantly higher peak heart rate and HRR compared with diabetic
      women. CONCLUSIONS: These results indicate that the benefit of cardiac
      rehabilitation in HRR is significantly lower in type 2 diabetic men. Improvement
      of HRR is not associated with diabetic status in women >/= 50 years old. The
      response to cardiac rehabilitation in women may appear to be influenced more by
      age at menopause rather than diabetes mellitus.

PMID- 20041360
TI  - Comparison of thyroid volume and goiter measured by means of ultrasonography and
      SPECT with use of 131I and 99m)c in smokers and non-smokers.
AB  - INTRODUCTION: The aim of the study was to estimate the influence of nicotine on
      thyroid volume according to patients' sex. MATERIAL AND METHODS: A group of 160
      patients with thyroid disorders in their past medical history was examined.
      Patients were divided into two groups: Group A contained 50 patients with goiter,
      where the volume of the thyroid was evaluated with use of US and (131)I-SPECT;
      group B contained 50 patients with goiter, where the volume of the thyroid was
      evaluated with use of US and (99m)Tc-SPECT. There were two control groups: Group
      A' contained 30 patients with normal volume of the thyroid gland shown by US and
      (131)I-SPECT, and group B' contained 30 patients with normal volume of the
      thyroid gland shown by US and (99m)Tc-SPECT. The patients from the examined and
      control groups were divided into two subgroups - smokers and non-smokers. US of
      the thyroid gland was made by means of an ALOKA SSD 500 device. SPECT was
      performed by means of a singke-headed gamma camera by Diacam. RESULTS: The
      average volume of thyroid gland measured by (131)I-SPECT and (99m)Tc-SPECT was
      significantly larger according to US in the examined and control groups in
      smokers and non-smokers. We did not show statistically significant correlations
      between levels of iodine uptake and volumes of goiter evaluated by US examination
      together with (131)I scintigraphy. CONCLUSIONS: Significant differences in
      average values of thyroid volume between smokers and non-smokers were not
      observed, which might suggest a lack of goitrogenic activity of tobacco smoke or
      indicates a potential goitrogenic influence not significant enough in the
      examined group.

PMID- 20041361
TI  - Homocysteine, folate, and cobalamin levels in hyperthyroid women before and after
      treatment.
AB  - INTRODUCTION: Hyperhomocysteinaemia is an independent risk factor for premature
      atherosclerotic vascular disease and venous thrombosis. Hypothyroidism is
      associated with mild hyperhomocysteinaemia. The aim of the present study was to
      assess plasma total homocysteine (tHcy) and its determinants (folate, cobalamin)
      in hyperthyroid patients before and after treatment. MATERIAL AND METHODS: Thirty
      hyperthyroid and thirty healthy premenopausal women were studied. The
      hyperthyroid patients were investigated in the untreated state and again after
      restoration of euthyroidism. The levels of homocysteine, folate, cobalamin, and
      thyroid stimulating hormone (TSH), free thyroxine (fT(4)), free triiodothyronine
      (fT(3)), and renal function were measured before and after treatment. RESULTS: In
      hyperthyroidism, tHcy was lower than in the control group. The serum level of
      folate was higher and serum cobalamin was lower in the hyperthyroid state.
      Following antithyroid drug therapy, tHcy significantly increased and folate
      decreased. The level of cobalamin remained unchanged. Univariate analysis in the
      hyperthyroid group indicated that tHcy significantly negatively correlated only
      with fT(3). CONCLUSIONS: Lower homocysteine levels in hyperthyroid state can be
      explained by the influence of thyroid hormone. High level of folate is only
      partially responsible for these changes.

PMID- 20041362
TI  - Iodine concentration in Polish milk - variations due to season and region.
AB  - INTRODUCTION: Iodine concentration was studied in Polish consumer milk. MATERIAL
      AND METHODS: The milk originated from 13 provincial cities and 65 dairy
      cooperatives located in Poland. RESULTS: Milk iodine concentration in the winter
      season of 2007-2008 was 146.8 mg/L, with a standard deviation for the provinces
      of 27.9 mg/L and variation coefficient of 19.0% (n = 66 samples). Iodine
      concentration for provincial cities ranged from 76.3 to 192.0 mg/L. It was
      highest in the milk samples from the Lubelskie province (191.9 mg/L) and lowest
      in the milk samples from Podlasie (113.8 mg/L). In the summer season, milk iodine
      concentration averaged 100.4 mg/L, with a standard deviation of 38.9 ig/L and
      variation coefficient of 38.8% (n = 27 samples). CONCLUSIONS: Iodine
      concentration for provincial cities ranged from 63.8 to 173.7 mg/L. Compared to
      the winter season, milk iodine concentration in the summer season was lower by an
      average of 25.2%, with a standard deviation of 4.3% (Kielce) to 52.2% (Wroclaw).

PMID- 20041363
TI  - [Isolation of pituitary autoantigen by affinity chromatography].
AB  - INTRODUCTION: In sera of pituitary disease patients and other autoimmune
      endocrine disease are detectable pituitary autoantibodies. Until now
      characterization of pituitary antigen is still unknown. The aim of our study was
      isolation and characterization of pituitary autoantigen by affinity
      chromatography. For isolation we have used microsomal fraction of human
      pituitary. MATERIAL AND METHODS: For immunoglobulins isolation have been used
      sera of pituitary disease, Addison disease and Graves-Basedow disease patients
      with detectable pituitary autoantibodies. For pituitary antigen isolation have
      been used microsomal fraction of human pituitary obtained by ultracentrifugation
      and solubilisation. Immunoglobulins isolation was performed on Sepharose 4B
      Protein A. Immunosorbent was performed on CNBr-activated Cl-4B Sepharose.
      Desorbtion was conducting by 0.2 mol/L glicine and 1 mol/L, 3 mol/L guanidine.
      The estimation of isolated proteins was performed by immunoblotting. RESULTS:
      Isolation of immunoglobulins from patients sera was done 12 times receiving from
      8.5 up to 13.5 mg of IgG from 1-1.5 ml of sera. In desorbtion we have received
      from 0.026 up to 0.150 mg of antigen proteins. For molecular weight estimation
      isolated proteins have been labeled by (125)I and run on SDS/PAGE with
      autoradiography. Autoradiography shown us two lines with 67 kDa and 55 kDa and
      low weight protein line. CONCLUSIONS: Isolation of pituitary autoantigen by
      affinity chromatography shown two different antigen proteins with 67 kDa and 55
      kDa.

PMID- 20041364
TI  - [Mood of individuals with Graves-Basedow's disease and Hashimoto's disease].
AB  - INTRODUCTION: Mood can be characterized as subjective, relatively long lasting
      emotional state. The impact of the mood on health can be considered in two
      aspects: mood as an intermediary factor/cause of disease or as its result. The
      aim of following paper was to define the mood of individuals with Graves
      Basedow's disease Hashimoto's disease in comparison to each other and in
      comparison to healthy individuals. MATERIAL AND METHODS: The study group
      consisted of 70 individuals with Graves-Basedow's disease (56 women and 14 men)
      and the same amount of healthy ones. The study group of Hashimoto's disease
      consisted of 54 individuals (46 women and 8 men) and the same amount of healthy
      ones. The patients filled out three psychological methods: Profile of Mood States
      (POMS), University of Wales Institute of Science and Technology Mood Adjective
      Check List (UMACL), a personal survey and an analysis of the medical
      documentation. RESULTS: Results indicate difference between individuals with
      Graves-Basedow's disease and healthy ones taking under consideration mood: anger
      and tension, dejection, embarrassment and vigor. There is no difference between
      individuals with Hashimoto's disease and healthy ones considering mood. There are
      differences between Graves-Basedow's disease and Hashimoto's disease regarding
      tension - anger. No differences have been claimed concerning criterions of health
      such as: time of duration of disease, complications, coexisting other diseases.
      Nevertheless the level of hormones is connected with the mood. CONCLUSIONS: In
      case of Graves-Basedow's disease has been claimed stronger anger, sadness,
      embarrassment and less vigor. Individuals with Hashimoto's disease are regarded
      as similar to the healthy ones, without features of forced depression,
      irritability or embarrassment. To sum up the mood of individuals among testing
      group is a result of disease.

PMID- 20041365
TI  - [The role of osteoprotegerin and vitamin D in thyroid pathology].
AB  - Hormonal dysfunction of thyroid gland manifests, among other, in bone tissue
      disorders. The evaluation of changes in bone is possible not only by using the
      classical markers of bone turnover. Very interesting chemical compounds are
      osteoprotegerin and vitamin D; their serum concentration among patients with
      thyroid disorders can show the range of changes in bone metabolism.
      Osteoprotegerin possess an ability of reduction of bone resorption. Vitamin D has
      several "nonclassical" mechanisms of action, also the possibility of interaction
      with endogenous thyroid hormones. The aim of this study is to review the current
      literature concerning the role of osteoprotegerin and vitamin D in thyroid
      pathology.

PMID- 20041366
TI  - [Metabolic syndrome and bone].
AB  - In recent years an increasing socioeconomic burden of two pressing problems has
      been observed: enormous prevalence of obesity and - along with aging of
      populations - great number of people affected with osteoporosis. Visceral
      obesity, expressed by increased waist circumference, is according to the latest
      guidelines a crucial component of metabolic syndrome (MS). So far the two
      entities have not been linked, as studies have proven beneficial effect of
      increased body weight on bone mineral density (BMD). It has been shown however,
      that adipose tissue is actually an endocrine tissue, secreting numerous
      biologically active substances that influence also bone. Moreover, an adipocyte
      and osteoblast derive from a common precursor cell. There is also increasing
      number of evidence showing common genetic determination of the diseases. Data
      from experimental and epidemiological studies proves that obesity itself as well
      as remaining components of MS might have negative influence on bone. BMD as well
      as fracture risk have been shown to be raised in patients diagnosed with MS. The
      same has been observed for high blood pressure. What's more, contradiction
      between high BMD and - simultaneously - high fracture risk in subjects with type
      2 diabetes has not been convincingly explained. The paper discusses reports and
      controversies on coexistence and interactions between MS and osteoporosis and its
      complications.

PMID- 20041367
TI  - [Difficulties in the diagnosis of ACTH-dependent Cushing's syndrome in a patient
      after left adrenalectomy and treated with glucocorticoids].
AB  - Cushing's syndrome (CS), that is a consequence of chronic excess of
      corticosteroides, is most frequently of iatrogenic origin. Corticotropin
      secreting pituitary adenomas are responsible for most cases of endogenous
      Cushing' s syndrome. Difficulties in the diagnosis and treatment of ACTH
      dependent Cushing's syndrome concern with localization of the source of
      pathological ACTH secretion, particularly when magnetic resonance imaging is
      unable to identify the pituitary microadenoma. In this paper we present the case
      of a patient with symptoms of Cushing's syndrome and describe problems with
      localization of the source of hypercortisolemia. The diagnostic process was
      additionally complicated by the treatment with corticosteroids, occasionally
      applied due to concomitant diseases. This delayed the right diagnosis and
      treatment.

PMID- 20041368
TI  - [Riedel's goitre - rare and difficult to diagnose reason for surgical treatment
      of goiters].
AB  - INTRODUCTION: The paper reports a female patient treated surgically for Riedel's
      goitre. A total of 4775 patients were treated surgically between 1 January 2000
      and 31 December 2007 for various types of goitres. Thyroiditis was diagnosed in
      193 (4.0%) cases. Among them Riedel's goitre was found in one (0.5%). CASE
      REPORT: A 51-year-old woman P.G. (case record No. 1377/2007) was admitted to our
      hospital with considerable dyspnea, both inspiratory and expiratory, accompanied
      by marked stridor and retrosternal goitre, the latter suspected of neoplasmic
      process. Thyroid gland was hard, its left lobe extending behind the sternum. No
      disorders in thyroid hormonal function or high antibody titre against thyroid
      peroxidase were observed. Ultrasonography revealed large thyroid gland with
      mediastinal invasion, nodulated and hypoechogenic. Fineneedle biopsy suggested
      thyroid colloidal tumor. X-ray of the chest and neck revealed wide upper portion
      of the mediastinum and narrow trachea. Laryngological examination confirmed
      paralysis of left vocal fold. The patient was operated under general endotracheal
      anesthesia. Both thyroid lobes were partially resected together with the isthmus,
      and malacic trachea was decompressed. No complications were observed during
      postoperative period. Paraffin histopathological examination confirmed the
      presence of Riedel's goitre. The patient was discharged in general good
      condition. She was under regular follow-up control and died 1.5 year after
      operation from further progress of the disease. CONCLUSIONS: Clinical course of
      Riedel's goitre may cause remarkable diagnostic problems, and requires a
      differentiation with thyroid malignant tumor. Surgical treatment of Riedel's
      goitres helps to quickly obtain correct diagnosis and improve both clinical
      condition and life comfort of the patients.

PMID- 20041369
TI  - [The difficulties in differential diagnosis of primary aldosteronism subtypes in
      women with strokes at a young age].
AB  - In patients with primary aldosteronism (PA), it is fundamental to distinguish
      between subtypes that benefit from different treatment. The authors describe
      difficulties in differential diagnosis in a case of 46 year old women with PA and
      two strokes in the past. Based on high plasma and urine aldosterone
      concentration, low plasma renin activity (PRA), very high aldosterone/PRA ratio
      and unilateral macroadenoma detected in computed tomography, aldosterone
      producing adenoma was diagnosed and the patient was performed unilateral
      adrenalectomy. Despite the surgical treatment the patient still presented with
      clinical and biochemical PA symptoms. Moreover, histological examination
      suggested adrenal hyperplasia, and laboratory tests were typical for
      glucocorticoid-remediable aldosteronism. Unfortunately, we didn't find a chimeric
      CYP 11beta1/CYP 11beta2 gene. Finally, bilateral adrenal hyperplasia was
      diagnosed and medical treatment with aldosterone antagonist was initiated.

PMID- 20041370
TI  - [Osteoporotic fractures].
AB  - The paper presents actual data concerning osteoporotic fractures (definitions,
      causes, epidemiologic and clinical data, consequences, treatment) particulary
      data about the most common fractures (distal forearm, vertebral and proximal hip
      fractures).

PMID- 20041371
TI  - [Peripheral precocious puberty].
AB  - The term precocious puberty is defined as the appearance of secondary sex
      characteristics before the age of 8 in girls and 9 in boys. There are two major
      forms of premature sexual maturation: gonadotrophin-dependent (central, or 'true'
      precocious puberty) and gonadotrophin- independent precocious puberty. The
      latter, also called peripheral precocious puberty, is characterized by increased
      production of sex steroids, causing the typical physical changes of puberty, in
      the absence of reactivation of the hypothalamic-pituitary axis. It may result
      from several different disorders including testotoxicosis, McCune-Albright
      syndrome, congenital adrenal hyperplasia, adrenal and gonadal tumours. The
      accumulation of knowledge regarding the pathogenesis of symptoms and the
      development of safe, effective treatment modalities have led to earlier
      intervention in patients with peripheral precocious puberty to prevent the
      decline in their psychosocial wellbeing, adult height and quality of life. We
      review the ethiopathogenesis, clinical picture, diagnosis and treatment of
      various disorders causing peripheral precocious puberty and provide the reader
      with current recommendations concerning approach to the patient with this health
      problem.

PMID- 20041372
TI  - [34(th) Annual Meeting of the European Thyroid Association, 5th-9th September
      2009, Lisbon Portugal].

PMID- 20041375
TI  - Clinical outcome study and radiological findings of Zweymuller metal on metal
      total hip arthroplasty. a follow-up of 6 to 15 years.
AB  - We report the clinical and radiological outcome of 99 Zweymuller metal on metal
      total hip arthroplasties in 84 patients followed up prospectively for a mean
      period of 9.5 (range, 6-15) years. There were 29 (34.5%) male and 55 (65.5%)
      female patients with a mean age of 62.85 years (range, 50-70 years) at the time
      of surgery. All patients had osteoarthritis. One acetabular component and one
      stem were revised due to aseptic loosening. One femoral stem was revised due to a
      periprosthetic fracture. HHS score improved from a preoperative mean of 62.56
      points (SD 8.87) to a final postoperative follow-up mean of 93.48 (SD 7.7).
      Cumulative success rate for both implants at 13 years, with aseptic loosening as
      the end point, was 97.05%, while for both implants at 13 years, with revision for
      any reason as the end point, it was 91.17%. Satisfactory results were observed
      with the use of this prosthesis.

PMID- 20041376
TI  - Large diameter metal-on-metal total hip arthroplasty for Crowe IV developmental
      dysplasia of the hip.
AB  - The short-term results of middle-aged patients with severe developmental
      dysplasia of the hip treated with subtrochanteric femoral shortening and
      cementless large diameter metal-on-metal total hip arthroplasty were
      retrospectively evaluated. Clinical and radiological results of 15 hips of 13
      patients with Crowe IV developmental dysplasia of the hip were enrolled in this
      study. The average follow-up period was 49 months (36-62 months). The average age
      of patients at the time of surgery was 45.5 years (range, 36-65 years).
      Radiographs were evaluated for component position, subsidence, loosening, and
      osteolysis. Intraoperatively, two patients had a small proximal femoral shaft
      split that was held with a cable wire. The average preoperative Harris hip score
      was 58; at 3 years, 82. Trendelenburg sign was negative in 11 hips at the last
      assessment. Loosening, subsidence, infection, dislocation, hypersensitivity and
      neurovascular complications were not observed. One hip had to be revised 1 year
      after surgery because of nonunion at the osteotomy site. Our study shows that
      large diameter metal-on-metal total hip arthroplasty, incorporating
      subtrochanteric femoral shortening, decreases dislocation rate and provides
      excellent results for the completely dislocated hip.

PMID- 20041377
TI  - Triple pelvic osteotomy for the treatment of residual hip dysplasia. Analysis of
      complications.
AB  - The aim of the paper was to present the results achieved with triple pelvic
      osteotomy in the treatment of residual hip dysplasia, with special interest in
      identifying recurrences and complications and how to avoid them. 60 patients (76
      hips) with developmental dysplasia of the hip (DDH), treated by the triple pelvic
      osteotomy according to Tonnis and modified by Vladimirov, were included in the
      study. Hips were evaluated radiologically with the center-edge (CE) angle, break
      of the Shenton-Menard arch and index of acetabular depth by Heyman-Herndon, and
      functionally using the Harris Hip Score (HHS). The postoperative results showed
      an average increase of the CE angle by a mean of 23.5+/-9.28 degrees, with a
      highly significant difference between the preoperative and final postoperative
      findings (t-test, t=-20.85, p<0.01). The mean HHS significantly improved
      (p<0.01). Total complication rate was 13,1%, divided in: 1,3% (one case) of
      triple nonunion of iliac, pubic and ischial bones, 7,9% (six cases) of double
      nonunion of pubic and ischial bones, 2,6% (two cases) of peroneal palsy and 1,3%
      (one case) of infection. In this study the triple pelvic osteotomy showed to be
      reliable for acetabular dysplasia in adolescent and young adult, alone or in
      association with proximal femoral osteotomy and/or great trochanter distal
      advancement.

PMID- 20041378
TI  - Large ball metal on metal hips obscure cup angle measurement on plain
      radiographs.
AB  - CT when compared to plain radiograph is known to be a more valid measure of
      acetabular component orientation. The validity of plain radiographs may be
      further compromised by large diameter metal femoral heads because of obscuration
      of the acetabular rim. We quantified this effect by measuring acetabular cup
      angles (inclination and version) of 49 metal on metal (MOM) hip resurfacings
      using plain radiographs and 3D CT based measurement. Bland-Altman plots revealed
      poor agreement between plain radiographic and CT based measurement with 2
      standard deviation limits of agreements of: +7 to -15 degrees for cup inclination
      angle; and +16 to -31 degrees for cup version angle. The large differences
      between plain radiographic and CT measurement of cup positions are probably due
      to the large diameter metal femoral head that can obscure the cup margin. We have
      used a metal artefact reduction CT protocol with a 3D imaging software package to
      overcome this problem and measure cup position relative to the Anterior Pelvic
      Plane.

PMID- 20041379
TI  - Changes in whole blood metal ion levels following resurfacing: serial
      measurements in a multi-centre study.
AB  - Seventy-seven patients implanted with unilateral resurfacing prosthesis were
      recruited from four centres. Serial whole blood samples were collected and ion
      levels were analysed. In most cases, the ion levels stabilized by 3 months. The
      24 month median ion levels were 1.49ug/l for chromium and cobalt. In
      approximately 50% of patients the increase in chromium and cobalt level was less
      than 1ug/l. There were 6 patients with abnormally high metal ion levels. Of these
      4 were significant outliers, had high ion levels that became apparent between 12
      and 24 months after implantation, and had a high cup abduction angle. Not all
      patients with high cup abduction angles demonstrated high levels. There were
      differences in ion levels between the four centres that correlated with variation
      in acetabular component placement. Variability in ion levels was seen with the
      same prosthesis, underscoring the importance of surgical technique, longitudinal
      analysis, and multi-centre trials.

PMID- 20041380
TI  - Hip resurfacing through a modified anterolateral approach, as compared with the
      Ganz trochanteric flip osteotomy: a two year follow-up study.
AB  - Hip resurfacing arthroplasty has conventionally been undertaken through the
      posterior approach. There has been evidence in the recently published literature
      to suggest that the posterior approach may compromise the blood supply to the
      femoral head, by disruption of the posterolateral hip capsule. Ganz et al have
      proposed the trochanteric 'flip' osteotomy through a lateral approach, to permit
      surgical dislocation of the hip without damaging the blood supply. The
      disadvantages, however, are that early full weight bearing is not permitted and
      there is an incidence of trochanteric delayed or non-union, which may require
      further treatment. We describe a technique of hip resurfacing through a modified
      anterolateral approach preserving the posterolateral capsular blood supply. We
      describe our experience using this approach, and compare the results with our
      previously used Ganz trochanteric osteotomy. At a mean follow-up of two years,
      the outcome scores were not significantly different, and both groups had similar
      abductor strength. There were two cases of delayed union in the Ganz group, one
      of which required revision; there were no complications in the modified
      anterolateral group.

PMID- 20041381
TI  - Results of total hip arthroplasties in the young patient; further evidence for a
      barrier against articular wear debris by hydroxyapatite coatings.
AB  - We examined the hypothesis that the circumferential osseous apposition around HA
      coated implants forms a protective barrier against articular wear debris. Sixty
      five hydroxyapatite-coated total hip arthroplasties in 57 patients (age <50years)
      with polyethylene-metal articulation were evaluated regarding PE-wear,
      osteolysis, and clinical outcome at a minimum of 10 years follow-up. There was no
      correlation between PE-wear and osteolysis of the femoral zones or cup zones I
      and III. A strong Pearson correlation was found between polyethylene wear and
      osteolysis around cup zone II, where the cup only consisted of polyethylene
      (p<0,01). The aseptic failure rate was 1.5% for the femoral component and 4.5%
      for the cup after 10 years of follow-up. The average Harris Hip Score was 90 and
      the average Engh score for fixation was 23 after 10 years . Around HA-coated
      parts of the prosthesis bone formation remained stable, regardless of the degree
      of polyethylene wear. The average linear polyethylene wear was 0,16 mm/year. The
      circumferential osseous apposition of the HA-coated implants possibly formed a
      protective barrier against articular wear debris. The use of cups with a backside
      gap resulted in PE-wear associated osteolysis in cup zone II and may be
      considered to be best avoided.

PMID- 20041382
TI  - Midterm results of cementless total hip replacement in rapidly destructive
      arthropathy and a review of the literature.
AB  - BACKGROUND AND PURPOSE: Rapidly destructive arthropathy (RDA) of the hip is a
      disease of unknown etiology characterized by a rapid destruction of the
      acetabular and femoral aspects of the hip joint. The purpose of this study was to
      assess the outcome of cementless total hip replacement in this category of
      patients. METHODS: A prospective study was performed of all cases of rapidly
      destructive arthropathy treated by cementless total hip replacement between 1998
      and 2005. There were 6 female patients (8 hips) meeting the criteria of RDA.
      Median age at surgery was 74 years (range 64-83). Using the Paprosky
      classification of acetabular defects, five hips had a type 2B acetabular defect
      and three a type 3A acetabular defect. In all cases a cementless prosthesis was
      used. In two cases a shelf plasty of the acetabulum was added. Radiographic and
      clinical follow-up was performed up to 9 years postoperatively (mean follow-up 69
      months, range 24-104 months). RESULTS: At radiographic follow-up, no signs of
      prosthetic loosening or migration were seen. Harris Hip Score improved from 25.8
      (SD 7.3, range 11-34) preoperatively to 88.3 (SD 9.7, range 71-98) at latest
      follow-up. CONCLUSION: Cementless total hip replacement in patients with rapidly
      destructive arthropathy led to a good result in a series of eight cases at
      midterm follow-up.

PMID- 20041383
TI  - 8-year follow-up after cementless hip arthroplasty with a second generation
      spongy metal total hip replacement.
AB  - We studied a consecutive series of 81 cementless total hip arthroplasties in 80
      patients using the second generation ESKA cementless spongy metal hip
      replacement. The study end-point was implant revision and both function as well
      as satisfaction with treatment outcome were assessed.Mean age at the time of
      surgery was 50.9 years [range 23-73]. No patient was lost to follow-up and 75
      patients (76 hips) could be included in the final analysis at a mean follow-up of
      7.9 years [range 7.0-10.0]. Survival rate without loosening as the end-point was
      100% for the femoral component and 99% for the acetabular component (one cup
      revision). Two cups and one stem had to be revised for recurrent dislocation,
      resulting in a total implant survival at follow-up of 99% for the femoral
      component and 96% for the acetabular component. Very good functional results were
      obtained with a mean Merle d' Aubigne score of 15.5 +/- 2.9 at 7.9 years after
      surgery. Satisfaction with treatment outcome was reported in 88%. 95% of patients
      would recommend the performed procedure to a friend. Peri-operative complications
      without revision occurred in eleven patients (14%).We report excellent survival
      rates of the cementless spongy metal hip arthroplasty at a mean follow-up of
      eight years, particularly considering the young age of many of the patients.

PMID- 20041384
TI  - Early results and patient satisfaction after total hip arthroplasty using a
      minimally invasive anterolateral approach.
AB  - Rehabilitation and patient satisfaction following a modified anterolateral
      approach for implantation of a total hip replacement (THR) were reviewed
      following 72 consecutive cases. The Harris Hip and Merle d'Aubigne Scores were
      recorded at 6 and 12 weeks postoperatively. The patient's satisfaction with
      regard to the surgical result and the need for analgesia for mobilization were
      recorded. Rehabilitation was assessed by postoperative crutch use.Significant
      improvements of the Harris Hip and Merle d'Aubigne scores were demonstrated. All
      patients thought their surgical outcome was good or better. 2 patients needed
      pain medicine on an irregular basis and 4 patients used crutches at 12 weeks.
      This study demonstrates patient satisfaction and satisfactory rehabilitation
      following a modified antero-lateral approach for minimally-invasive implantation
      of THR.

PMID- 20041385
TI  - Surgical repair of chronic tears of the hip abductor mechanism.
AB  - Lateral sided hip pain frequently presents to the orthopaedic clinic. The most
      common cause of this pain is trochanteric bursitis. This usually improves with
      conservative treatment. In a few cases it doesn't settle and warrants further
      investigation and treatment. We present a series of 28 patients who underwent MRI
      scanning for such pain, 16 were found to have a tear of their abductors. All 16
      underwent surgical repair using multiple soft tissue anchors inserted into the
      greater trochanter of the hip to reattach the abductors. There were 15 females
      and 1 male. All patients completed a self-administered questionnaire pre
      operatively and 1 year post-operatively. Data collected included: A visual
      analogue score for hip pain, Charnley modification of the Merle D'Aubigne and
      Postel hip score, Oxford hip score, Kuhfuss score of Trendelenburg and SF36
      scores.Of the 16 patients who underwent surgery 5 had a failure of surgical
      treatment. There were 4 re ruptures, 3 of which were revised and 1 deep infection
      which required debridement. In the remaining 11 patients there were statistically
      significant improvements in hip symptoms. The mean change in visual analogue
      score was 5 out of 10 (p=0.0024) The mean change of Oxford hip score was 20.5
      (p=0.00085). The mean improvement in SF-36 PCS was 8.5 (P=0.0020) and MCS 13.7
      (P=0.134). 6 patients who had a Trendelenburg gait pre-surgery had normal gait 1
      year following surgery.We conclude that hip abductor mechanism tear is a frequent
      cause of recalcitrant trochanteric pain that should be further investigated with
      MRI scanning. Surgical repair is a successful operation for reduction of pain and
      improvement of function. However there is a relatively high failure rate.

PMID- 20041386
TI  - A new radiographic method of measuring femoral offset. The Sundsvall method.
AB  - Restoring femoral offset (FO) is an important factor for the success of total hip
      arthroplasty (THA). However, earlier methods of measuring FO do not take in
      consideration the positioning of the acetabular component. In this study we
      introduce and evaluate a new radiological method of measuring FO as the
      horizontal distance between the femoral axis and the midline of the pelvis, at
      the height of the lateral tip of the greater trochanter.Ten patients operated
      with THA underwent a plain radiographic examination of the pelvis (AP view) and a
      CT scanogram for the pelvis and lower limbs (scout view). The radiological FO
      measurement using the new method was initially compared to FO measurement on CT
      scanogram and subsequently to the traditional radiological method of measuring
      FO. We tested the interobserver reliability and the intraobserver reproducibility
      of the new method.We found an excellent agreement between the new radiological
      method and the CT measurement and between the new radiological method and the
      traditional radiological method. We also found an excellent interobserver
      reliability and an intraobserver reproducibility of the new method. We believe
      the new method is easier than and as reliable as previously described methods.

PMID- 20041387
TI  - Is there an association between epiphyseal scar and osteonecrosis of the femoral
      head?
AB  - PURPOSE: To investigate statistical association between epiphyseal scar and
      osteonecrosis of the femoral head (ONFH) with magnetic resonance (MR) imaging.
      PATIENTS AND METHODS: We retrospectively reviewed 71 consecutive patients who
      underwent MR imaging of bilateral hips that showed nontraumatic ONFH. There were
      110 hips with ONFH and 31 normal hips; one hip received bipolar arthroplasty
      before the MR studies. All cases of ONFH had typical MR findings. The epiphyseal
      scars in the femoral head were classified as type I (a sealed-off scar) or type
      II (a perforated scar). Bone marrow edema, if present, in the proximal femur was
      identified on coronal T2-weighted or STIR MR images. RESULTS: The type of femoral
      epiphyseal scar was clearly delineated in 97 hips. In cases with ONFH, a type I
      scar occurred in 46 hips (64%), and a type II scar in 26 hips (36%). In cases of
      ONFH with bone marrow edema, 69% of hips (24/35) had a type I scar and 31% of
      hips (11/35) had a type II scar. There was no statistical association between the
      type of epiphyseal scar and ONFH, regardless of staging (P=0.29), or the type of
      scar and bone marrow edema (P=0.42). CONCLUSION: There is not a significant
      statistical association between a sealed-off scar and ONFH.

PMID- 20041388
TI  - Femoro-acetabular impingement: can indirect MR arthrography be considered a valid
      method to detect endoarticular damage? A preliminary study.
AB  - To assess the effectiveness of indirect Magnetic Resonance arthrography (i-MRa)
      in the detection of chondral and labral lesions related to femoro-acetabular
      impingement (FAI) a series of 21 hip joints in 17 patients with a clinical
      diagnosis of FAI were examined either with standard MR imaging, i-MRa and direct
      MR arthrography (d-MRa). Sensitivity and accuracy of i-MRa in detecting chondral,
      labral and tardive lesions were calculated and compared with standard MR. The
      agreement in detecting endoarticular damage between i-MRa and d-MRa and the
      interobserver agreement was assessed by K statistic (p<0.05). Finally the
      presence of trocanteric bursitis was evaluated. I-MRa showed higher values of
      both sensivity and accuracy than standard MR in detecting chondral damage, with
      an increase to 92% for the first item and 95% for the second. The same was
      noticed in labrum evaluation with an increase to 88% and 90% respectively. The
      level of agreement between i-MRa and d-MRa in detection of chondral lesions was
      excellent, substantial for the labral damage and absolute for early
      osteoarthritic changes. An excellent interobserver agreement resulted in
      detection of both chondral and labral damages with i-MRa. In 6 hips (28,5%) we
      also found the presence of peri-trochanteric soft tissue inflammation that
      indicated the possibility of extrarticular involvement in FAI. Indirect-MRa can
      be considered a valid method of assessing endoarticular damage related to FAI, in
      comparison to d-MRa. It should be performed instead of standard MR if d-MRa is
      not available.

PMID- 20041389
TI  - Early catastrophic failure of a porous-coated acetabular cup due to bead
      shedding. A case report.
AB  - We present a patient in whom an uncemented porous-coated acetabular cup underwent
      early catastrophic failure due to debonding and was successfully managed with a
      revision total hip arthroplasty. Early bead shedding of an acetabular cup leading
      to a sudden component failure requiring revision surgery is a rare event.

PMID- 20041390
TI  - Dislocation of a total hip arthroplasty following hip arthroscopy.
AB  - Arthroscopy is used increasingly in the diagnosis and treatment of hip disorders
      of both natural and prosthetic hip joints. Complications tend to be transient and
      self-resolving. This is the first report of a hip arthroscopy destabilizing a
      prosthetic hip resulting in dislocation of the joint.

PMID- 20041391
TI  - Late small intestine perforation after cementless total hip arthroplasty.
AB  - We report a case of late small intestine perforation by an acetabular cup
      fixation screw after total hip arthroplasty (THA). A 79-year-old-woman underwent
      THA for hip osteoarthritis 13 years previously at another hospital. Although the
      acetabular cup fixation screw protruded into the pelvis, she had no symptoms. She
      later presented with peritonitis and was admitted to the hospital and prescribed
      antibiotic therapy. Computed tomography showed that the screw was adjacent to the
      intestine and was the likely cause of her peritonitis. After the peritonitis
      healed, she was referred to our hospital for surgical treatment of the screw.
      During laparotomy, we performed a resection of the intra-pelvic portion of the
      screw. The screw perforated the small intestine, so a small intestinal resection
      was also performed. The patient had an uneventful recovery.

PMID- 20041392
TI  - Unusual case of osteosynthesis failure in a hip fracture: side-plate pull-out.
AB  - Osteoporotic hip fractures are common in our setting. Poor bone quality favors
      complications of the osteosynthesis procedures used to treat these patients. Lag
      screw cut-out through the femoral head is not uncommon (2%), but pull-out of side
      plate screws is very unusual. We present the case of a patient with a stable
      osteoporotic fracture treated by osteosynthesis using a four-hole plate, who
      presented with a pull-out following a low-energy fall.

PMID- 20041396
TI  - Double trisomy revisited--a multicenter experience.

PMID- 20041397
TI  - Twin-to-twin transfusion syndrome presenting at early stages: is there still a
      possible role for amnioreduction?
AB  - OBJECTIVE: To assess the rate of resolution or progression after first line
      treatment with amnioreduction and related outcome of pregnancies with twin-to
      twin transfusion syndrome (TTTS) diagnosed at stages I-II. METHOD: Data on 34
      monochorionic diamniotic twin pregnancies presenting with TTTS at stage I-II
      before 26 weeks of gestation were collected retrospectively (1999-2006). All
      patients underwent at least one amnioreduction. The outcome and the results of
      neurological follow-up of surviving twins were analysed in relation to the
      regression or progression of the disease after treatment. RESULTS: Fourteen cases
      (41%) resolved after treatment while 18 cases (53%) progressed. In two patients
      immediate complications occurred within one week after amnioreduction; at least
      one infant survived in 85.3% of cases and there was double survival in 58.8%.
      Double survival was significantly better in cases that regressed (85.7%) compared
      with those cases that progressed (44.4%). None of the surviving infants in the
      group of cases with regression showed major neurological abnormalities.
      CONCLUSION: In our study, one-third of patients with stage I-II TTTS regressed
      after a single amnioreduction, and pregnancies with resolution of TTTS usually
      had a favourable outcome.

PMID- 20041398
TI  - Determination of enoxacin and ofloxacin by capillary electrophoresis with
      electrochemiluminescence detection in biofluids and drugs and its application to
      pharmacokinetics.
AB  - A novel and sensitive method for the simultaneous determination of enoxacin and
      ofloxacin has been established using capillary electrophoresis (CE) coupled with
      electrochemiluminescence (ECL) detection based on the ECL enhancement of tri(2,2
      bipyridyl)ruthenium(II). The conditions for sample solvent type, CE separation
      and ECL detection were investigated systematically. The analytes were well
      separated and detected within 7 min. The limits of detection (S/N = 3) of
      enoxacin and ofloxacin are 9.0 x 10(-9) and 1.6 x 10(-8) mol/L, respectively. The
      precisions (RSD%) of intraday and interday are less than 2.1 and 4.0%,
      respectively. The limits of quantitation (S/N = 10) of enoxacin and ofloxacin are
      3.2 x 10(-7) and 5.4 x 10(-7) mol/L in human urine samples and 4.1 x 10(-7) and
      6.9 x 10(-7) mol/L in human serum samples, respectively. The recoveries of
      enoxacin and ofloxacin at different concentration levels in human urine, serum
      and eye drop samples are between 94.0 and 106.7%. The proposed method was
      successfully applied to the determination of the enoxacin and ofloxacin in human
      urine, serum and eye drop samples and the monitoring of pharmacokinetics of
      ofloxacin in human body.

PMID- 20041399
TI  - Determination of carboplatin in canine plasma by high-performance liquid
      chromatography.
AB  - Carboplatin is an antineoplastic drug administered to treat different tumoral
      conditions in canine oncology. The objective of this study was to validate a high
      performance chromatographic (HPLC) method which could be applied in canine
      pharmacokinetic studies. Following ultrafiltration using a Centrifree device,
      standards, quality controls and plasma samples were separated by isocratic
      reversed-phase HPLC on an Inertsil ODS-2 (250 x 4.6 mm i.d.) analytical column
      and quantified using UV detection at 220 nm. The mobile phase was potassium
      phosphate (pH 4.5), with a flow-rate of 1.0 mL/min. The procedure produced a
      linear curve (r(2) > 0.999) over the concentration range 1-200 microg/mL. The
      lower limit of quantification was 1 microg/mL. The intra-assay and inter-assay
      precision was approximately 90%. The overall recovery was approximately 90%. The
      method was illustrated with a preliminary pharmacokinetic analysis on nine dogs
      treated with carboplatin at our hospital. Carboplatin disposition followed a
      monocompartmental structure in dogs and was characterized by a short half-life
      (50 min).

PMID- 20041400
TI  - A fast, reproducible and low-cost method for sequence deconvolution of 'on-bead'
      peptides via 'on-target' maldi-TOF/TOF mass spectrometry.
AB  - A novel approach to high-throughput sequence deconvolution of on-bead small
      peptides (MW < 2000 Da) using on-target MALDI-TOF/TOF instrumentation is
      presented. Short peptides of pentamer and octamer length, covalently attached to
      TentaGel polystyrene beads through a photolabile linker, were placed onto the
      MALDI target, apportioned with suitable matrix (2,5-dihydroxybenzoic acid) and
      then hit with the instrument laser (Nd : YAG, 355 nm). This induced easy and
      highly reproducible photochemical cleavage, desorption (MS mode) and
      fragmentation (MS/MS mode). Peptide fragments were identified with a mass
      accuracy of 0.1 Da of the expected values. This technique significantly
      accelerates the sequence determination of positive peptide hits obtained from
      random combinatorial libraries when screening against biological targets, paving
      the way for a rapid and efficient method to identify molecular imaging ligands
      specific to pathological targets in cancer and other diseases.

PMID- 20041401
TI  - Molecular signatures of nonalcoholic fatty liver disease: the present and future.

PMID- 20041402
TI  - Bicarbonate secretion of mouse cholangiocytes involves Na(+)-HCO(3)(-)
      cotransport in addition to Na(+)-independent Cl(-)/HCO(3)(-) exchange.
AB  - Bicarbonate secretion from cholangiocytes is required for appropriate adjustment
      of primary canalicular bile along the biliary tract. In human and rat
      cholangiocytes, bicarbonate secretion is mediated by anion exchanger (AE) 2, an
      electroneutral Na(+)-independent Cl(-)/HCO(3) (-) AE also involved in
      intracellular pH (pH(i)) regulation. In Ae2(a,b)-deficient mice, pH(i) is
      increased in lymphocytes and fibroblasts, whereas it is surprisingly normal in
      cholangiocytes. Here, we analyze the mechanisms for HCO(3) (-) secretion in
      cultured Ae2(a,b) (+/+) and Ae2(a,b) (-/-) mouse cholangiocytes by
      microfluorimetric measurement of pH(i) changes upon established perfusion
      maneuvers. Cl(-) withdrawal by isethionate-based perfusions showed that Ae2(a,b)
      (+/+) but not Ae2(a,b) (-/-) mouse cholangiocytes can display Cl(-)/HCO(3) (-)
      exchange, which is therefore entirely mediated by Ae2. Nevertheless, simultaneous
      withdrawal of Cl(-) and Na(+) revealed that mouse cholangiocytes possess an
      additional transport activity for HCO(3) (-) secretion not observed in control
      rat cholangiocytes. Propionate-based maneuvers indicated that this supplemental
      Na(+)-driven HCO(3) (-)-secreting activity is Cl(-)-independent, consistent with
      a Na(+)-HCO(3) (-) cotransport (NBC). NBC activity is greater in Ae2(a,b) (-/-)
      than Ae2(a,b) (+/+) mouse cholangiocytes, and membrane-depolarization experiments
      showed that it is electrogenic. Consistent with the potential role of Slc4a4/Nbc1
      as the involved transporter, Ae2(a,b) (-/-) mouse cholangiocytes exhibit up
      regulated expression of this electrogenic NBC carrier. Whereas Ae2-mediated Cl(
      )/HCO(3) (-) exchange in Ae2(a,b) (+/+) mouse cholangiocytes is stimulated by
      cyclic adenosine monophosphate (cAMP) and acetylcholine, the NBC activity is down
      regulated by cAMP and adenosine triphosphate (ATP) in Ae2(a,b) (-/-) mouse
      cholangiocytes. Polarized Ae2(a,b) (-/-) mouse cholangiocytes placed in Ussing
      chambers show decreased (but not abolished) cAMP-dependent Cl(-) current and
      increased ATP-dependent/Ca(2+)-activated Cl(-) secretion, which run in parallel
      with decreased cystic fibrosis transmembrane conductance regulator messenger RNA
      expression and increased intracellular Ca(2+) levels. CONCLUSION: Bicarbonate
      secretion in mouse cholangiocytes involves two differentially regulated
      activities: Ae2-mediated Cl(-)/HCO(3) (-) exchange and Na(+)-HCO(3) (-)
      cotransport.

PMID- 20041403
TI  - Emergency adult-to-adult living-donor liver transplantation for acute liver
      failure in a hepatitis B virus endemic area.
AB  - The outcomes of patients with acute liver failure (ALF) vary greatly according to
      etiology. Emergency adult-to-adult living-donor liver transplantation (adult
      LDLT) would help address the shortage of available organs for patients with ALF,
      especially in hepatitis B virus (HBV)-endemic areas. We analyzed a prospective
      database of 110 consecutive adult patients with ALF. ALF was defined as sudden
      development of severe coagulopathy and encephalopathy within 26 weeks of onset of
      symptoms. In about 90% of patients, ALF was caused by etiologies that usually
      result in poor outcomes, including HBV infection (37%). Three cases (3%) were
      associated with acetaminophen overdose. Of the 99 patients listed for emergency
      liver transplantation, four (4%) underwent deceased-donor liver transplantation
      (DDLT), and 40 (40%) underwent adult LDLT. The 1-year survival rate of adult LDLT
      patients was 85%. Of the 55 patients listed but not transplanted, 45 (82%) died
      within a median of 7 days (range, 1-90 days). Multivariate analysis showed that
      adult LDLT (hazard ratio [HR] 0.10, P < 0.01) and DDLT (HR 0.12, P = 0.04) were
      associated with decreased mortality, whereas older age (HR 1.03, P = 0.01) and
      higher Model for End-stage Liver Disease (MELD) (HR 1.03, P = 0.04) was
      associated with increased mortality of patients. There was no living donor
      mortality. Eight (17.8%) and three (6.7%) living donors experienced grade 1 and 2
      complications, respectively. CONCLUSION: Emergency adult LDLT can be performed
      expeditiously and safely for patients with ALF, and greatly improves the survival
      rate. As the window during which transplantation is possible is limited,
      emergency adult LDLT should be considered one of the first-line treatment options
      in patients with ALF, especially in regions in which ALFs are caused by
      etiologies associated with poor outcome and the supply of organs is severely
      limited.

PMID- 20041404
TI  - Human immunodeficiency virus and liver disease: conference proceedings.

PMID- 20041405
TI  - Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of
      hepatocellular carcinoma.
AB  - Based on microarray data, we have previously shown a significant down-regulation
      of miR-29 in hepatocellular carcinoma (HCC) tissues. To date, the role of miR-29
      deregulation in hepatocarcinogenesis and the signaling pathways by which miR-29
      exerts its function and modulates the malignant phenotypes of HCC cells remain
      largely unknown. In this study, we confirmed that reduced expression of miR-29
      was a frequent event in HCC tissues using both Northern blot and real-time
      quantitative reverse-transcription polymerase chain reaction. More interestingly,
      we found that miR-29 down-regulation was significantly associated with worse
      disease-free survival of HCC patients. Both gain- and loss-of-function studies
      revealed that miR-29 could sensitize HCC cells to apoptosis that was triggered by
      either serum starvation and hypoxia or chemotherapeutic drugs, which mimicked the
      tumor growth environment in vivo and the clinical treatment. Moreover,
      introduction of miR-29 dramatically repressed the ability of HCC cells to form
      tumor in nude mice. Subsequent investigation characterized two antiapoptotic
      molecules, Bcl-2 and Mcl-1, as direct targets of miR-29. Furthermore, silencing
      of Bcl-2 and Mcl-1 phenocopied the proapoptotic effect of miR-29, whereas
      overexpression of these proteins attenuated the effect of miR-29. In addition,
      enhanced expression of miR-29 resulted in the loss of mitochondrial potential and
      the release of cytochrome c to cytoplasm, suggesting that miR-29 may promote
      apoptosis through a mitochondrial pathway that involves Mcl-1 and Bcl-2.
      CONCLUSION: Our data highlight an important role of miR-29 in the regulation of
      apoptosis and in the molecular etiology of HCC, and implicate the potential
      application of miR-29 in prognosis prediction and in cancer therapy.

PMID- 20041407
TI  - An identification of novel therapy for human hepatocellular carcinoma by using
      human induced pluripotent stem cells.

PMID- 20041406
TI  - Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and
      clinical implications.
AB  - Obesity is associated with an increased risk of nonalcoholic fatty liver disease
      (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of
      hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater
      than the rate of fatty acid oxidation and export (as triglyceride within very low
      density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride
      (IHTG) represents an imbalance between complex interactions of metabolic events.
      The presence of steatosis is associated with a constellation of adverse
      alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that
      abnormalities in fatty acid metabolism, in conjunction with adipose tissue,
      hepatic, and systemic inflammation, are key factors involved in the development
      of insulin resistance, dyslipidemia, and other cardiometabolic risk factors
      associated with NAFLD. However, it is not clear whether NAFLD causes metabolic
      dysfunction or whether metabolic dysfunction is responsible for IHTG
      accumulation, or possibly both. Understanding the precise factors involved in the
      pathogenesis and pathophysiology of NAFLD will provide important insights into
      the mechanisms responsible for the cardiometabolic complications of obesity.

PMID- 20041408
TI  - Loss of hepatocyte nuclear factor 1alpha function in human hepatocellular
      adenomas leads to aberrant activation of signaling pathways involved in
      tumorigenesis.
AB  - Hepatocellular adenomas (HCAs) are benign liver tumors that usually develop in
      women who are taking oral contraceptives. Among these tumors, biallelic
      inactivating mutations of the hepatocyte nuclear factor 1alpha (HNF1A)
      transcription factor have been frequently identified and in rare cases of
      hepatocellular carcinomas developed in noncirrhotic liver. Because HNF1A meets
      the genetic criteria of a tumor suppressor gene, we aimed to elucidate the
      tumorigenic mechanisms related to HNF1alpha inactivation in hepatocytes. We
      searched for signaling pathways aberrantly activated in human HNF1A-mutated HCA
      (H-HCA) using a genome-wide transcriptome analysis comparing five H-HCA with four
      normal livers. We validated the main pathways by quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and western blotting in a large
      series of samples. Then, we assessed the role of HNF1alpha in the observed
      deregulations in hepatocellular cell models (HepG2 and Hep3B) by silencing its
      endogenous expression using small interfering RNA. Along with the previously
      described induction of glycolysis and lipogenesis, H-HCA also displayed
      overexpression of several genes encoding growth factor receptors, components of
      the translation machinery, cell cycle, and angiogenesis regulators, with, in
      particular, activation of the mammalian target of rapamycin (mTOR) pathway.
      Moreover, estradiol detoxification activities were shut down, suggesting a
      hypersensitivity of H-HCA to estrogenic stimulation. In the cell model,
      inhibition of HNF1alpha recapitulated most of these identified transcriptional
      deregulations, demonstrating that they were related to HNF1alpha inhibition.
      CONCLUSION: H-HCA showed a combination of alterations related to HNF1alpha
      inactivation that may cooperate to promote tumor development. Interestingly, mTOR
      appears as a potential new attractive therapeutic target for treatment of this
      group of HCAs.

PMID- 20041409
TI  - Growing old gracefully: caring for the 90-year-old liver in the 40-year-old
      transplant recipient.

PMID- 20041410
TI  - Hepatocellular carcinoma: sorafenib before liver transplantation?

PMID- 20041411
TI  - Serum cytokeratin-18 fragment level: a noninvasive biomarker for not only
      nonalcoholic steatohepatitis, but also alcoholic steatohepatitis.

PMID- 20041412
TI  - Interplay of hepatic and myeloid signal transducer and activator of transcription
      3 in facilitating liver regeneration via tempering innate immunity.
AB  - Liver regeneration triggered by two-thirds partial hepatectomy is accompanied by
      elevated hepatic levels of endotoxin, which contributes to the regenerative
      process, but liver inflammation and apoptosis remain paradoxically limited. Here,
      we show that signal transducer and activator of transcription 3 (STAT3), an
      important anti-inflammatory signal, is activated in myeloid cells after partial
      hepatectomy and its conditional deletion results in an enhanced inflammatory
      response. Surprisingly, this is accompanied by an improved rather than impaired
      regenerative response with increased hepatic STAT3 activation, which may
      contribute to the enhanced liver regeneration. Indeed, conditional deletion of
      STAT3 in both hepatocytes and myeloid cells results in elevated activation of
      STAT1 and apoptosis of hepatocytes, and a dramatic reduction in survival after
      partial hepatectomy, whereas additional global deletion of STAT1 protects against
      these effects. CONCLUSION: An interplay of myeloid and hepatic STAT3 signaling is
      essential to prevent liver failure during liver regeneration through tempering a
      strong innate inflammatory response mediated by STAT1 signaling.

PMID- 20041413
TI  - Modulatory effects of curcumin and resveratrol on lung carcinogenesis in mice.
AB  - The aim of the present study is to explore the chemopreventive potential of
      curcumin and resveratrol during promotional phase of benzo(a)pyrene (BP) induced
      lung carcinogenesis in mice. The mice were segregated into five groups which
      included normal control, BP-treated, BP+curcumin-treated, BP+resveratrol-treated
      and BP+curcumin+resveratrol-treated groups. The BP treatment resulted in a
      significant increase in the levels of lipid peroxidation (LPO). On the other
      hand, reduced glutathione (GSH) levels and the activities of superoxide dismutase
      (SOD) were found to be significantly decreased following BP treatment.
      Administration of curcumin to BP-treated mice decreased the levels of LPO
      significantly. Further, treatment of resveratrol to BP-treated mice significantly
      elevated the activities of SOD. Combined treatment of curcumin and resveratrol,
      kowever, showed significant improvement in LPO and GSH levels as well as in the
      activities of SOD. Histo-architectural studies showed well-differentiated signs
      of lung carcinogenesis following BP administration to mice. Although treatments
      with resveratrol and curcumin given separately to BP-treated mice showed
      appreciable improvement in the histo-architecture of the lung, combined treatment
      resulted in a noticeable improvement in the lung histo-architecture.

PMID- 20041414
TI  - Efficacy of blackcurrant oil soft capsule, a Chinese herbal drug, in
      hyperlipidemia treatment.
AB  - Blackcurrant oil soft capsule (BOSC) is an effective and safe herbal medicine for
      the treatment of hyperlipidemia and has been approved for the market in China. No
      studies have been performed, however, to confirm whether BOSC is effective in
      reducing the serum lipid level in a large-scale ordinary or special patient
      population. In this study, we conducted an observational study at five
      investigative sites that was designed to further investigate the efficacy of BOSC
      on serum lipid level lowering in a large-scale target patient population and
      include a relative factors analysis for the serum lipid decrease. Serum total
      cholesterol (TC), triglycerides (TGs) and high density lipoprotein-cholesterol
      (HDL-C) were measured before and after drug administration. TC and TGs were
      detected by enzymatic analysis, while HDL-C was detected by PTA-Mg(2+)
      precipitation. A total of 2,154 dyslipidemic patients were recruited and took
      BOSC 1.8 g b.i.d. every day for 6 weeks. In terms of serum lipid lowering, the
      overall curative rate was 37.19%, the marked effective rate was 52.28% and the
      effective rate was 79.06%. The corresponding effective rate of TC, TGs and HDL-C
      was 80.98%, 78.28% and 67.07%, respectively. Multivariate analyses with
      adjustment for centers, gender and age indicated that BOSC was almost ineffective
      in patients with a disease course <36 months (OR: 0.467, 95% CI: 0.359-0.607) and
      was effective in mild hyperlipidemia (OR: 3.176, 2.535-3.978) and in subjects
      with lower BMIs (BMI <24: 3.472, 2.171-5.552; BMI between 24 and 28: 2.310, 1.832
      2.911 compared with BMI >or= 28). No serious adverse events were reported during
      the study period. Therefore, we conclude that BOSC is effective in decreasing TC
      and TG levels and in increasing the serum HDL-C level, especially in mildly
      hyperlipidemic patients and those with a lower BMI. Moreover, because it is a
      natural raw material, BOSC may be safer and more effective in the treatment of
      hyperlipidemia.

PMID- 20041415
TI  - Four carotenoids from Pittosporum tobira protect primary cultured rat cortical
      cells from glutamate-induced toxicity.
AB  - We observed that an aqueous extract of this medicinal plant exhibited significant
      neuroprotection against glutamate-induced toxicity in primary cultured rat
      cortical cells from methanol extracts of the seeds of P. tobira. To further
      clarify the underlying neuroprotective mechanism(s) of this observed effect, we
      isolated and identified various active fractions and components. By using such
      fractionation procedures, four known carotenoids compounds--tobiraxanthins A1,
      A2, A3, and B--were isolated from the n-hexane fraction of methanol extracts from
      the seeds of P. tobira. Among these four compounds, tobiraxanthins B exhibited
      significant neuroprotective activity against glutamate-induced neurotoxicity, as
      indicated by a cell viability of approximately 50%, at concentrations ranging
      from 0.1 microM to 10 microM. These findings indicate that, the neuroprotective
      effects of P. tobira might be due to the inhibition of glutamate-induced toxicity
      by carotenoids present in the plant.

PMID- 20041416
TI  - beta-secretase inhibitory effects of furanocoumarins from the root of Angelica
      dahurica.
AB  - In the course of screening antidementia agents from natural products, five beta
      secretase (BACE1) inhibitors were isolated from the root extract of Angelica
      dahurica (Umbelliferae). They were identified as furanocoumarins, isoimperatorin
      (1), imperatorin (2), (+)-oxypeucedanin (3), (+)-byakangelicol (4) and (+)
      byakangelicin (5). Among them, compounds 2 and 4 showed significant inhibitory
      activity against beta-secretase (BACE1) with IC(50) values of 91.8 +/- 7.5 and
      104.9 +/- 2.4 microM, respectively. Compounds 1-5 inhibited BACE1 activity in a
      dose-dependent manner.

PMID- 20041417
TI  - In vitro antiviral activity of neem (Azardirachta indica L.) bark extract against
      herpes simplex virus type-1 infection.
AB  - Herpes simplex virus type 1 (HSV-1) causes significant health problems from
      periodical skin and corneal lesions to encephalitis. We report here that an
      aqueous extract preparation from the barks of neem plant Azardirachta indica acts
      as a potent entry inhibitor against HSV-1 infection into natural target cells.
      The neem bark extract (NBE) significantly blocked HSV-1 entry into cells at
      concentrations ranging from 50 to 100 microg/ml. The blocking activity of NBE was
      observed when the extract was pre-incubated with the virus but not with the
      target cells, suggesting a direct antiHSV-1 property of the neem bark. Further,
      virions treated with NBE failed to bind the cells which implicate a role of NBE
      as an attachment step blocker. Cells treated with NBE also inhibited HSV-1
      glycoprotein-mediated cell-cell fusion and polykaryocytes formation suggesting an
      additional role of NBE at the viral fusion step. These findings open a potential
      new avenue for the development of NBE as a novel antiherpetic microbicide.

PMID- 20041418
TI  - Psychopathology and well-being in civilian survivors of war seeking treatment: a
      follow-up study.
AB  - The goal of the current study was to examine types of exposure to traumatic
      events and affective and anxiety disorders of 81 civilian war survivors seeking
      treatment for war-related stress almost one decade following the war in the area
      of former conflict. Furthermore, the study investigated changes in symptoms of
      mental health and in well-being amongst these individuals during a treatment
      period of 6 months. The results indicated that civilian war survivors seeking
      treatment reported multiple war-related traumatic events and high levels of
      psychiatric morbidity. Individuals assessed at follow-up (n = 67) reported no
      change in post-traumatic stress symptoms or psychological well-being, but
      improvement in symptoms of depression, overall psychiatric distress and quality
      of life. The only significant difference between participants classified as
      achieving clinically significant improvement as compared with those who did not
      achieve such change was in less symptom severity of depression, post-traumatic
      stress, general distress and higher psychological well-being at the time of first
      assessment. Neither the assessment of initial diagnoses nor war or post-war
      trauma types emerged as significantly different amongst the two groups.

PMID- 20041419
TI  - Relating therapy for people who hear voices: perspectives from clients, family
      members, referrers and therapists.
AB  - Current psychological models of voice hearing emphasise the personal meaning that
      individuals attribute to the voice hearing experience. Recent developments in
      theory and research have highlighted the importance of the relationship between
      the hearer and the voice. This study aims to contribute to this area of research,
      by exploring the experience and usefulness of a new form of 'Relating Therapy'
      that aims to modify distressing relationships with voices. Semi-structured
      interviews were conducted with ten participants and explored the experience and
      usefulness of a pilot of Relating Therapy: three therapists, three voice hearers,
      two relatives and two referrers. Interviews were transcribed and analysed using
      Interpretative Phenomenological Analysis. Three themes that emerged from the
      analysis are presented for discussion: engaging with the therapeutic model;
      developing a new relating style; and how change is described and defined by
      participants. This study is consistent with the growing body of theory and
      research that highlights the interpersonal nature of the voice hearing
      experience. It also offers tentative support for a therapeutic framework that
      aims to modify distressing relationships with voices as a means of bringing about
      positive change. Clinical implications and areas for future research are
      outlined. 

PMID- 20041420
TI  - Self-concept and attributions about other women in women with a history of
      childhood sexual abuse.
AB  - Self-concept literature and literature on childhood sexual abuse (CSA) suggests
      that women with a history of CSA may have particular ways of perceiving
      themselves, which, as well as impacting upon relationships within their everyday
      lives, may also have implications for therapy; whether this is on an individual
      basis or within a group. This research investigated self-concept and attributions
      about other women using an adapted version of the self-concept sorting task.
      Three groups of women were compared: women with a history of CSA, women
      experiencing depressed mood but without a history of CSA and a healthy non
      clinical comparison group of hospital staff. To some extent the current findings
      supported previous studies indicating that women attempting to cope with the
      consequences of a history of CSA have a negative self-concept. However, there was
      evidence to suggest that certain self-aspects are protective or protected.
      Similarly, there is some support for previous evidence of difficult relationships
      with mothers. Possible explanations for these findings were discussed and areas
      for future research suggested.

PMID- 20041421
TI  - Is mindfulness-based therapy an effective intervention for obsessive-intrusive
      thoughts: a case series.
AB  - Despite the efficacy of cognitive-behavioural interventions in improving the
      experience of obsessions and compulsions, some people do not benefit from this
      approach. The present research uses a case series design to establish whether
      mindfulness-based therapy could benefit those experiencing obsessive-intrusive
      thoughts by targeting thought-action fusion and thought suppression. Three
      participants received a relaxation control intervention followed by a six-session
      mindfulness-based intervention which emphasized daily practice. Following therapy
      all participants demonstrated reductions in Yale-Brown Obsessive-Compulsive Scale
      scores to below clinical levels, with two participants maintaining this at follow
      up. Qualitative analysis of post-therapy feedback suggested that mindfulness
      skills such as observation, awareness and acceptance were seen as helpful in
      managing thought-action fusion and suppression. Despite being limited by small
      participant numbers, these results suggest that mindfulness may be beneficial to
      some people experiencing intrusive unwanted thoughts and that further research
      could establish the possible efficacy of this approach in larger samples.

PMID- 20041422
TI  - An investigation into the experience of self-conscious emotions in individuals
      with bipolar disorder, unipolar depression and non-psychiatric controls.
AB  - There has been little research into the association of shame and other self
      conscious emotions in bipolar disorder, although there is evidence linking shame
      to various psychopathologies. OBJECTIVES: This research investigates the levels
      of shame in individuals with bipolar disorder. DESIGN AND METHODS: A cross
      sectional design was used to compare 24 individuals with a diagnosis of bipolar
      disorder to a clinical control group of 18 individuals with unipolar depression,
      and 23 age-matched non-psychiatric controls on measures of mood (Beck Depression
      Inventory [BDI] and Self Report Manic Inventory [SRMI]) and of self-conscious
      emotions (Internalized Shame Scale and Test of Self-Conscious Affect). RESULTS:
      Higher levels of trait shame and lower guilt-proneness were found in the bipolar
      group. Higher levels of shame-proneness were found in the unipolar group in
      comparison to the bipolar and control groups. BDI scores positively correlated
      with trait shame and shame-proneness, and accounted for a large proportion of the
      variance in these scores. SRMI scores positively correlated with trait
      (internalized) shame and negatively correlated with guilt-proneness. CONCLUSIONS:
      There was evidence for the presence of shame within bipolar disorder, but this
      differed to the evidence for shame in individuals with unipolar depression.
      Clinical implications are discussed. 

PMID- 20041423
TI  - Propolis immunomodulatory action in vivo on Toll-like receptors 2 and 4
      expression and on pro-inflammatory cytokines production in mice.
AB  - Propolis is a bee product and its immunomodulatory action has been the subject of
      intense investigation lately. The recent discovery and characterization of the
      family of Toll-like receptors (TLR) have triggered a great deal of interest in
      the field of innate immunity due to their crucial role in microbial recognition
      and development of the adaptive immune response. This work aimed to evaluate
      propolis's effect on TLR-2 and TLR-4 expression and on the production of pro
      inflammatory cytokines (IL-1beta and IL-6). Male BALB/c mice were treated with
      propolis (200 mg/kg) for three consecutive days, and TLR-2 and TLR-4 expression
      as well as IL-1beta and IL-6 production were assessed in peritoneal macrophages
      and spleen cells. Basal IL-1beta production and TLR-2 and TLR-4 expression were
      increased in peritoneal macrophages of propolis-treated mice. TLR-2 and TLR-4
      expression and IL-1beta and IL-6 production were also upregulated in the spleen
      cells of propolis-treated mice. One may conclude that propolis activated the
      initial steps of the immune response by upregulating TLRs expression and the
      production of pro-inflammatory cytokines in mice, modulating the mechanisms of
      the innate immunity.

PMID- 20041424
TI  - Protection of human HepG2 cells against oxidative stress by the flavonoid
      epicatechin.
AB  - Flavanols, such as epicatechin (EC), constitute an important part of the human
      diet; they can be found in green tea, grapes and cocoa and possess different
      biological activities such as antioxidant, anti-inflammatory and
      anticarcinogenic. This study investigated the potential chemo-protective effect
      of EC against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on
      human HepG2 cells. Cell viability by lactate dehydrogenase assay and markers of
      oxidative status: reduced glutathione (GSH), malondialdehyde (MDA), reactive
      oxygen species (ROS), glutathione peroxidase (GPx) and glutathione reductase (GR)
      were evaluated. Pretreatment of cells with EC for 20 h prevented the enhanced
      cell damage and GPx and GR activities as well as the decrease in GSH induced by t
      BOOH. The increased ROS generation induced by t-BOOH was also partly prevented by
      a pretreatment for 20 h with EC. In addition, pretreatment of cells with EC for
      20 h recovered the t-BOOH-induced MDA concentration to control values. A
      pretreatment for 2 h with EC did not reduce cell damage but partly recovered GSH,
      reduced ROS levels and muffled the increase of GPx and GR after exposure to t
      BOOH. Treatment of HepG2 cells with concentrations of EC in the micromolar range
      confers a significant protection against oxidative stress.

PMID- 20041425
TI  - Effects of Echinacea extracts on macrophage antiviral activities.
AB  - Type I interferons are a class of cytokines synthesized by leukocytes such as
      macrophages that limit viral replication. We hypothesized that one mechanism
      whereby Echinacea spp. extracts may enhance immunity is through modulating
      interferon-associated macrophage pathways. We used herpes simplex viral infection
      in the murine macrophage cell line RAW264.7 and monitored virus-induced cell
      death, interferon secretion, and two intracellular proteins that indicate
      activation of interferon pathways. Cells were incubated with control media or
      extracts from four different species (E. angustifolia, E. purpurea, E.
      tennesseensis, E. pallida). Cells incubated with extracts prior to infection
      showed very modest enhancement of viability, and no increase in the secretion of
      interferons alpha or beta as compared to control cells. Virus-infected
      macrophages treated with extracts from E. purpurea showed a small (<2-fold)
      induction of guanylate binding protein (GBP) production, but no effect of
      extracts from other species was observed. In virus-infected cells, all the
      extracts increased the amount of inducible nitric oxide synthase (iNOS) protein,
      and this effect varied by type of extraction preparation. Together, these results
      suggest that any potential antiviral activities of Echinacea spp. extracts are
      likely not mediated through large inductions of Type I interferon, but may
      involve iNOS.

PMID- 20041426
TI  - Pharmacological basis for the medicinal use of Zanthoxylum armatum in gut,
      airways and cardiovascular disorders.
AB  - This study describes the gut, airways and cardiovascular modulatory activities of
      Zanthoxylum armatum DC. (Rutaceae) to rationalize some of its medicinal uses. The
      crude extract of Zanthoxylum armatum (Za.Cr) caused concentration-dependent
      relaxation of spontaneous and high K(+) (80 mM)-induced contractions in isolated
      rabbit jejunum, being more effective against K(+) and suggestive of Ca(++)
      antagonist effect, which was confirmed when pretreatment of the tissues with
      Za.Cr shifted Ca(++) concentration-response curves to the right, like that caused
      by verapamil. Za.Cr inhibited the castor-oil-induced diarrhea in mice at 300-1000
      mg/kg. In rabbit tracheal preparations, Za.Cr relaxed the carbachol (1 microM)
      and high K(+)-induced contractions, in a pattern similar to that of verapamil. In
      isolated rabbit aortic rings, Za.Cr exhibited vasodilator effect against
      phenylephrine (1 microM) and K(+)-induced contractions. When tested in guinea pig
      atria, Za.Cr caused inhibition of both atrial force and rate of spontaneous
      contractions, like that caused by verapamil. These results indicate that
      Zanthoxylum armatum exhibits spasmolytic effects, mediated possibly through
      Ca(++) antagonist mechanism, which provides pharmacological base for its
      medicinal use in the gastrointestinal, respiratory and cardiovascular disorders.

PMID- 20041427
TI  - Cornin ameliorates cerebral infarction in rats by antioxidant action and
      stabilization of mitochondrial function.
AB  - This study was conducted to investigate the efficacy of cornin, an iridoid
      glycoside, in an experimental cerebral ischemia induced by middle cerebral artery
      occlusion (MCAO) and reperfusion (I/R), and to elucidate the potential mechanism.
      Adult male Sprague-Dawley rats were subjected to MCAO for 1 h, then reperfusion
      for 23 h. Behavioral tests were used to evaluate the damage to central nervous
      system. The cerebral infarct volume and histopathological damage were assessed to
      evaluate the brain pathophysiological changes. Spectrophotometric assay methods
      were used to determine the activities of superoxide dismutase (SOD) and
      glutathione-peroxidase (GPx). Contents of malondialdehyde (MDA), the generation
      of reactive oxygen species (ROS) as well as respiratory control ratio and
      respiratory enzymes of the brain mitochondria were also determined. The results
      showed that cornin significantly decreased neurological deficit scores, and
      reduced cerebral infarct volume and degenerative neurons. Meanwhile, cornin
      significantly increased the brain ATP content, improved mitochondrial energy
      metabolism, inhibited the elevation of MDA content and ROS generation, and
      attenuated the decrease of SOD and GPx activities in brain mitochondria. These
      findings indicate that cornin has protective potential against cerebral ischemia
      injury and its protective effects may be due to amelioration of cerebral
      mitochondrial function and its antioxidant property.

PMID- 20041428
TI  - Pycnogenol treatment of acute hemorrhoidal episodes.
AB  - We investigated the efficacy of orally and topically applied Pycnogenol for the
      management of acute hemorrhoidal attacks in a controlled, randomized study with
      84 subjects. Within less than 48 h of onset of an acute attack, patients were
      enrolled and signs and symptoms were scored. This evaluation was repeated after
      seven days' treatment and again seven days following treatment cessation. The
      decrease in scores was significantly more pronounced in the Pycnogenol-treated
      groups than in the control group given placebo (p < 0.05), showing the efficacy
      of Pycnogenol for relieving signs and symptoms of acute external hemorrhoids. In
      a group of patients given topical (0.5%) Pycnogenol in addition to oral
      Pycnogenol the improvement in symptoms set in significantly faster and was more
      pronounced. The most prominent symptom, hemorrhoidal bleeding, was completely
      absent in all patients treated with Pycnogenol for seven days and also at the 14
      days follow-up. In contrast, bleedings were still observed in the control group
      during the two weeks follow-up. This study indicates that Pycnogenol, both in
      oral and in topical form, is effective for controlling this common, disabling
      health problem. The application of Pycnogenol eases the management of acute
      hemorrhoidal attacks and help avoid bleedings.

PMID- 20041429
TI  - Crocetin inhibits cell cycle G1/S transition through suppressing cyclin D1 and
      elevating p27kip1 in vascular smooth muscle cells.
AB  - Crocetin is a natural carotenoid compound isolated from Gardenia jasminoids
      Ellis. Our previous study shows that crocetin inhibits angiotensin II (Ang II)
      induced vascular smooth muscle cells (VSMCs) proliferation. To further explore
      the mechanism by which crocetin inhibits VSMCs proliferation, in the present
      study we examined the effect of crocetin on cell cycle progression and cell cycle
      regulatory proteins. Flow cytometry analysis showed that Ang II elicited
      significant increase in the percentage of VSMCs in the S phase, with a
      concomitant decline in the percentage of VSMCs in the G(0)/G(1) phase. However,
      on pretreatment of VSMCs with crocetin, the percentage of VSMCs in the S phase
      decreased, while that in the G(0)/G(1) phase increased significantly. In
      addition, Ang II-induced increase of cell proliferation index was also decreased
      by crocetin. Western blotting analysis indicated that crocetin markedly inhibited
      the protein expression of cyclin D1 but not cyclin E. Crocetin also increased the
      level of cyclin-dependent kinase inhibitor (CDKI) p27(kip1) but not CDKI
      p21(waf1/cip1). In conclusion, our present results suggest that the inhibition of
      cell cycle G(1)/S transition in VSMCs by crocetin can be attributed, at least in
      part, to its suppression of cyclin D1 and elevation of CDKI p27(kip1).

PMID- 20041430
TI  - Pharmacokinetics of bilobalide, ginkgolide A and B after administration of three
      different Ginkgo biloba L. preparations in humans.
AB  - A sensitive LC-ESI-MS method with a solid-phase extraction was established for
      the determination of bilobalide, ginkgolide A and ginkgolide B in human plasma;
      bioavailability and pharmacokinetics of three different Ginkgo biloba L.
      preparations have been investigated. The preparations used in the present single
      dose pharmacokinetic study were different formulations of Ginkgo biloba L.
      extracts (Geriaforce tincture, new Ginkgo fresh plant extract tablets and EGb
      761) with various excipients. The analysis of Ginkgo terpene lactones was
      performed by LC-MS on a Zorbax SB-C18 column. The mobile phase consisted of water
      + 0.1% acetic acid and methanol 68/32 (v/v) to 49/51 (v/v) at a flow rate of 200
      microL/min. Bilobalide, ginkgolide A and ginkgolide B were monitored using the
      selected-ion monitoring (SIM) mode at m/z of 325, 453 and 423, respectively.The
      amounts of the active compounds (terpene lactones) in the administered products
      were in the low-mg range per dose. The assay method was successfully applied to
      the study of the pharmacokinetics and bioavailability of bilobalide, ginkgolide A
      and ginkgolide B in humans. The resulting maximum concentrations (median) of
      bilobalide, ginkgolide A and ginkgolide B in plasma after administration of the
      maximum daily dose of the different Ginkgo products were 3.53, 3.62, and 1.38
      ng/mL respectively after administration of Geriaforce tincture; 11.68, 7.36, and
      4.18 ng/mL, respectively after taking Ginkgo fresh plant extract tablets; and
      26.85, 16.44, 9.99 ng/mL, respectively after administration of EGb 761 tablets.
      These data are relevant to demonstrate relative bioavailabilities of different
      Ginkgo biloba L. preparations (Geriaforce tincture, new Ginkgo fresh plant
      extract tablets and EGb 761).

PMID- 20041431
TI  - Effect of taxifolin glycoside on atopic dermatitis-like skin lesions in NC/Nga
      mice.
AB  - Increased levels of eosinphils, IgE, IL-4, 5, and 13 and pro-inflammatory factors
      (COX-2, iNOS) are observed in patients with atopic dermatitis (AD). Taxifolin 3-O
      beta-D-glucopyranoside (TAX) from the roots of Rhododendron mucronulatum (RM) was
      examined to determine whether its immunomodulatory effect was applicable for
      treating atopic dermatitis.A total of 7 groups of NC/Nga mice with AD were
      treated by topical application or intraperitoneal injection of TAX for 4 weeks.
      Follow-up evaluations were done to assess the changes in clinical observations,
      eosinophil counts, and levels of IgE, cytokines, COX-2 and iNOS.In the clinical
      observation during the experimental period, TAX treatment significantly reduced
      the severity of AD-like lesions induced in NC/Nga mice. Eosinophil and IgE levels
      decreased after treatment of the animals with TAX. TAX may thus be associated
      with improvement of eosinophil-related allergic diseases. The expression of
      cytokines (IL-4, 5 and 13) was significantly inhibited in the TAX-treated group,
      suggesting that TAX might play an immunoregulatory role associated with AD. In RT
      PCR, iNOS and COX-2 expression levels were reduced in the TAX-treated group. In
      western blotting, the expression levels of iNOS and COX-2 were also reduced in
      the TAX-treated group.These findings suggest that TAX is effective for the
      treatment of AD by preventing the production of inflammatory cytokines and by
      reducing skin inflammation.

PMID- 20041432
TI  - Lycopene protects the structure of the small intestine against gamma-radiation
      induced oxidative stress.
AB  - The small intestine displays numerous morphological and functional alterations
      after exposure to ionizing radiations. Oxidative stress and changes in monoamines
      levels may contribute toward some of these alterations. The objective of the
      current work is to evaluate the efficacy of lycopene on radiation-induced damage
      in the small intestine. Lycopene (5 mg/kg BW) was given to male albino rats, via
      gavages for 7 days before whole body exposure to gamma ray (6 Gy). Irradiated
      animals, sacrificed 7 days after irradiation, showed sloughing villi, ulcers, and
      ruptured goblet cells, shrinkage of submucosa layers, more fibers and
      fibroblasts. Histopathological changes were associated with a significant
      increase in thiobarbituric acid reactive substances (TBARS) and alteration in
      xanthine oxidoreductase system (XOR). In parallel, significant decreases in
      reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT)
      activities were recorded. Gamma irradiation has also induced a significant
      decrease in the level of monoamines: serotonin (5-HT), dopamine (DA),
      norepinephrine (NE), and epinephrine (EPI) associated with an increase in
      monoamine-oxidase (MAO) activity. Lycopene pretreatment has significantly
      improved the oxidant/antioxidant status, which was associated with significant
      regeneration of the small intestine, and improved monoamines levels. Based on
      these results, it is concluded that lycopene may protect the small intestine
      against radiation-induced damage.

PMID- 20041433
TI  - Antihepatotoxic activity of Saussurea lappa extract on D-galactosamine and
      lipopolysaccharide-induced hepatitis in mice.
AB  - The effects of aqueous-methanol extract of Saussurea lappa Clarke root (Sl.Cr)
      was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS)
      induced hepatitis in mice. Co-administration of D-GalN (700 mg/kg) and LPS (1
      microg/kg) significantly raised the plasma transaminase levels (ALT/AST) as
      compared to the control group (p < 0.05). Pretreatment of mice with different
      doses of Sl.Cr (150, 300 and 600 mg/kg) significantly prevented the D-GalN and
      LPS-induced rise in plasma levels of ALT and AST in a dose-dependent manner (p <
      0.05). Post-treatment with Sl.Cr (600 mg/kg) significantly restricted the
      progression of hepatic damage induced by D-GalN and LPS (p < 0.05). The
      improvement in plasma enzyme levels was further verified by histopathology of the
      liver, which showed improved architecture, absence of parenchyma congestion,
      decreased cellular swelling and apoptotic cells in treatment groups as compared
      to the toxin group of animals. These data indicate that the Sl.Cr exhibits
      hepatoprotective effect in mice and this study rationalize the traditional use of
      this plant in liver disorders.

PMID- 20041434
TI  - EMF acts on rat bone marrow mesenchymal stem cells to promote differentiation to
      osteoblasts and to inhibit differentiation to adipocytes.
AB  - The use of electromagnetic fields (EMFs) to treat nonunion fractures developed
      from observations in the mid-1900s. Whether EMF directly regulates the bone
      marrow mesenchymal stem cells (MSCs), differentiating into osteoblasts or
      adipocytes, remains unknown. In the present study, we investigated the roles of
      sinusoidal EMF of 15 Hz, 1 mT in differentiation along these separate lineages
      using rat bone marrow MSCs. Our results showed that EMF promoted osteogenic
      differentiation of the stem cells and concurrently inhibited adipocyte formation.
      EMF increased alkaline phosphatase (ALP) activity and mineralized nodule
      formation, and stimulated osteoblast-specific mRNA expression of RUNX2, ALP,
      BMP2, DLX5, and BSP. In contrast, EMF decreased adipogenesis and inhibited
      adipocyte-specific mRNA expression of adipsin, AP-2, and PPARgamma2, and also
      inhibited protein expression of PPARgamma2. These observations suggest that
      commitment of MSCs into osteogenic or adipogenic lineages is influenced by EMF.

PMID- 20041435
TI  - Estimation of whole-body SAR from electromagnetic fields using personal exposure
      meters.
AB  - In this article, personal electromagnetic field measurements are converted into
      whole-body specific absorption rates for exposure of the general public. Whole
      body SAR values calculated from personal exposure meter data are compared for
      different human spheroid phantoms: the highest SAR values (at 950 MHz) are
      obtained for the 1-year-old child (99th percentile of 17.9 microW/kg for electric
      field strength of 0.36 V/m), followed by the 5-year-old child, 10-year-old child,
      average woman, and average man. For the 1-year-old child, whole-body SAR values
      due to 9 different radiofrequency sources (FM, DAB, TETRA, TV, GSM900 DL, GSM1800
      DL, DECT, UMTS DL, WiFi) are determined for 15 different scenarios. An SAR matrix
      for 15 different exposure scenarios and 9 sources is provided with the personal
      field exposure matrix. Highest 95th percentiles of the whole-body SAR are equal
      to 7.9 microW/kg (0.36 V/m, GSM900 DL), 5.8 microW/kg (0.26 V/m, DAB/TV), and 7.1
      microW/kg (0.41 V/m, DECT) for the 1-year-old child, with a maximal total whole
      body SAR of 11.5 microW/kg (0.48 V/m) due to all 9 sources. All values are below
      the basic restriction of 0.08 W/kg for the general public. 95th percentiles of
      whole-body SAR per V/m are equal to 60.1, 87.9, and 42.7 microW/kg for GSM900,
      DAB/TV, and DECT sources, respectively. Functions of the SAR versus measured
      electric fields are provided for the different phantoms and frequencies, enabling
      epidemiological and dosimetric studies to make an analysis in combination with
      both electric field and actual whole-body SAR.

PMID- 20041436
TI  - Sinusoidal ELF magnetic fields affect acetylcholinesterase activity in cerebellum
      synaptosomal membranes.
AB  - The effects of extremely low frequency magnetic fields (ELF-MF) on
      acetylcholinesterase (AChE) activity of synaptosomal membranes were investigated.
      Sinusoidal fields with 50 Hz frequency and different amplitudes caused AChE
      activity to decrease about 27% with a threshold of about 0.74 mT. The decrease in
      enzymatic activity was independent of the time of permanence in the field and was
      completely reversible. Identical results were obtained with exposure to static MF
      of the same amplitudes. Moreover, the inhibitory effects on enzymatic activity
      are spread over frequency windows with different maximal values at 60, 200, 350,
      and 475 Hz. When synaptosomal membranes were solubilized with Triton, ELF-MF did
      not affect AChE activity, suggesting the crucial role of the membrane, as well as
      the lipid linkage of the enzyme, in determining the conditions for inactivation.
      The results are discussed in order to give an interpretation at molecular level
      of the macroscopic effects produced by ELF-MF on biological systems, in
      particular the alterations of embryo development in many organisms due to
      acetylcholine accumulation.

PMID- 20041439
TI  - Cytomegalovirus in intensive care.

PMID- 20041441
TI  - Defective interfering viruses and their potential as antiviral agents.
AB  - Defective interfering (DI) virus is simply defined as a spontaneously generated
      virus mutant from which a critical portion of the virus genome has been deleted.
      At least one essential gene of the virus is deleted, either in its entirety, or
      sufficiently to make it non-functional. The resulting DI genome is then defective
      for replication in the absence of the product(s) of the deleted gene(s), and its
      replication requires the presence of the complete functional virus genome to
      provide the missing functions. In addition to being defective DI virus suppresses
      production of the helper virus in co-infected cells, and this process of
      interference can readily be observed in cultured cells. In some cases, DI virus
      has been observed to attenuate disease in virus-infected animals. In this
      article, we review the properties of DI virus, potential mechanisms of
      interference and progress in using DI virus (in particular that derived from
      influenza A virus) as a novel type of antiviral agent.

PMID- 20041442
TI  - Recognition of viral nucleic acids in innate immunity.
AB  - Viral infections are detected by sensor molecules, which initiate innate
      antiviral responses, including the activation of type I interferons (IFNs) and
      proinflammatory cytokines. These cytokines are responsible for not only
      inhibiting viral replication in infected cells but also regulating the induction
      of adaptive immunity, leading to the swift eradication of viruses. Recent
      advances in the identification of pathogen receptors in the innate immune system
      have revealed that distinct types of sensors play a role in the detection of
      viral nucleic acids in different ways; Toll-like receptors (TLRs), which detect
      viral DNA or RNA in endosomal compartments in immune cells, retinoic acid
      inducible gene-I (RIG-I)-like receptors (RLRs), which recognise viral RNA in the
      cytoplasm, and DNA sensors, which detect cytoplasmic viral DNA. Since these
      sensors have to exclusively recognise viral infections, it is intriguing to
      understand how they distinguish self nucleic acids from foreign viral ones. Here,
      we review the current knowledge of the recognition of viral nucleic acids by
      these sensor molecules and the signal transduction machinery.

PMID- 20041443
TI  - Swine-origin pandemic H1N1 influenza virus-like particles produced in insect
      cells induce hemagglutination inhibiting antibodies in BALB/c mice.
AB  - Recent outbreaks of influenza A highlight the importance of rapid and sufficient
      supply for pandemic and inter-pandemic vaccines. Classical manufacturing methods
      for influenza vaccines fail to satisfy this demand. Alternatively, cell culture
      based production systems and virus-like particle (VLP)-based technologies have
      been established. We developed swine-origin pandemic H1N1 influenza VLPs
      consisting of hemagglutinin (A/California/04/2009) and matrix protein.
      Hemagglutinin and matrix protein were co-expressed in insect cells by the
      baculovirus expression system. VLPs were harvested from infection supernatants,
      purified and used for intraperitoneal immunization of BALB/c mice. Immunization
      induced high serum antibody titers against A/California/04/2009 as well as
      hemagglutination inhibiting antibodies. Additionally, we compared VLP production
      in two different insect cell lines, Sf9 and BTI-TN5B1-4 (High Five). Taken
      together VLPs represent a potential strategy for the fight against new pandemic
      influenza viruses.

PMID- 20041444
TI  - Defense mechanisms against toxic phytochemicals in the diet of domestic animals.
AB  - Plant secondary metabolites (PSMs) are non-nutritional components that occur in
      numerous feed materials and are able to exert toxic effects in animals. The
      current article aims to summarize innate defense strategies developed by
      different animal species to avoid excessive exposure to PSMs. These mechanisms
      include pre-systemic degradation of PSMs by rumen microbiota, the intestinal
      barrier including efflux transporters of monogastric species, as well as pre
      hepatic and intra-hepatic biotransformation processes. These physiological
      barriers determine systemic exposure and ultimately the dose-dependent adverse
      effects in the target animal species. Considering the large number of potentially
      toxic PSMs, which makes an evaluation of all individual PSMs virtually
      impossible, such a mechanism-oriented approach could improve the predictability
      of adverse effects and support the interpretation of clinical field observations.
      Moreover, mechanistic data related to tissue disposition and excretion pathways
      of PSMs for example into milk, could substantially support the assessment of the
      risks for consumers of foods derived from PSM-exposed animals.

PMID- 20041445
TI  - Liquid chromatography with accurate mass measurement on a triple quadrupole mass
      spectrometer for the identification and quantification of N-lactoyl ethanolamine
      in wine.
AB  - In this addendum to the original article [de Rijke, E., Ruisch, B.J., Bouter, N.,
      Konig, T., Liquid chromatography with accurate mass measurement on a triple
      quadrupole mass-spectrometer for the identification and quantification of N
      lactoyl ethanolamine in wine, Mol. Nutr. Food Res., 2006, 50, 351-355] a method
      is described to demonstrate that no potential cross-contamination from the
      reference target molecule had given rise to an incorrect positive identification
      of N-lactoyl ethanolamine in wine.

PMID- 20041446
TI  - The Japanese toxicogenomics project: application of toxicogenomics.
AB  - Biotechnology advances have provided novel methods for the risk assessment of
      chemicals. The application of microarray technologies to toxicology, known as
      toxicogenomics, is becoming an accepted approach for identifying chemicals with
      potential safety problems. Gene expression profiling is expected to identify the
      mechanisms that underlie the potential toxicity of chemicals. This technology has
      also been applied to identify biomarkers of toxicity to predict potential
      hazardous chemicals. Ultimately, toxicogenomics is expected to aid in risk
      assessment. The following discussion explores potential applications and features
      of the Japanese Toxicogenomics Project.

PMID- 20041447
TI  - LC-MS identification of derivatized free fatty acids from adipocere in soil
      samples.
AB  - Free fatty acids were derivatized as amides (DFFA) by reaction with (R)-(+)-1
      phenylethylamine, using a simple, fast and robust reaction scheme. A HPLC method
      with diode array and ESI MS detection was developed for the analysis of the
      derivatized substances. Six fatty acids were used in the method development:
      myristic, linoleic, palmitic, oleic, margaric and stearic acids. Under these
      conditions the elution of the DFFA are well resolved with retention times raging
      from 6.9 to 16.0 min. Fatty acids were extracted from cemetery soil and from
      adipocere formation experimental soils using a Soxhlet extraction, using as
      solvent ether/dichloromethane (1:1). Each DFFA is characterized by three m/z
      peaks: molecular weight of the substance; molecular weight of a dimer of the
      substance; the molecular weight of the dimer plus the atomic mass of sodium. The
      analysis of soil samples detected the six fatty acids used in the method
      developed plus palmitoleic and pentadecanoic. Beside this set of eight fatty
      acids other 13 fatty acids were detected in trace quantities or only in some
      soils and some were tentatively assigned as: 10-hydroxystearic, myristoleic,
      heptadecenoic and arachidic acids.

PMID- 20041449
TI  - Influence of pressure on the retention of sugars in hydrophilic interaction
      chromatography.
AB  - Pressure can influence the retention of analytes in hydrophilic interaction
      chromatography as well as in RP chromatography. We demonstrate that the retention
      of sugars in hydrophilic interaction chromatography decreases with pressure, and
      interpret the observation as a gain in solvation, or more specifically hydration,
      as the sugar molecules enter the water-rich stationary phase.

PMID- 20041448
TI  - Development and optimization of the SPE procedure for determination of
      pharmaceuticals in water samples by HPLC-diode array detection.
AB  - This paper focuses on the investigation of different types of SPE sorbents for
      the preconcentration of eight veterinary pharmaceuticals from water samples. The
      pharmaceuticals studied were sulfamethazine, sulfadiazine, sulfaguanidine,
      trimethoprim, oxytetracycline, enrofloxacin, norfloxacin and penicillin
      G/procaine. Five different SPE materials (Strata-X, Strata-X-C, Strata SDB-L,
      Strata C8 and Strata C18) from Phenomenex were compared with Oasis HLB with a
      view to obtaining the best cartridges for all pharmaceuticals investigated.
      Extraction efficiency was determined by HPLC with diode array detection (DAD).
      HPLC-DAD separation and quantification of the selected pharmaceuticals were
      carried out under gradient elution by a binary mixture of 0.01 M oxalic acid and
      ACN based on cyano modified column (LiChrosphere 100 CN) from Merck. Strata-X
      provided the best results in the preconcentration of 100 mL water samples,
      yielding average pharmaceutical recoveries of higher than 90%, except for
      sulfaguanidine (76.1%). The developed Strata-X-HLPC-DAD method was validated and
      applied, for the efficient investigation of reverse osmosis/nanofiltration
      membranes and for the removal of these eight pharmaceuticals from the production
      wastewater samples. NF90 and XLE membranes were shown to be the best for the
      rejection of all investigated pharmaceuticals.

PMID- 20041450
TI  - Isolation and purification of macrocyclic components from Penicillium
      fermentation broth by high-speed counter-current chromatography.
AB  - In this paper, high-speed counter-current chromatography (HSCCC), assisted with
      ESI-MS, was first successfully applied to the preparative separation of three
      macrolide antibiotics, brefeldin A (12.6 mg, 99.0%), 7'-O-formylbrefeldin A (6.5
      mg, 95.0%) and 7'-O-acetylbrefeldin A (5.0 mg, 92.3%) from the crude extract of
      the microbe Penicillium SHZK-15. Considering the chemical nature and partition
      coefficient (K) values of the three target compounds, a two-step HSCCC isolation
      protocol was developed in order to obtain products with high purity. In the two
      step method, the crude ethyl acetate extract was first fractionated and resulted
      in two peak fractions by HSCCC using solvent system n-hexane/ethyl
      acetate/methanol/water (HEMWat) (3:7:5:5 v/v/v/v), then purified using solvent
      systems HEMWat (3:5:3:5 v/v/v/v) and HEMWat (7:3:5:5 v/v/v/v) for each fraction.
      The purities and structures of the isolated compounds were determined by HPLC, X
      ray crystallography, ESI-MS and NMR. The results demonstrated that HSCCC is a
      fast and efficient technique for systematic isolation of bioactive compounds from
      the microbes.

PMID- 20041451
TI  - Targeted therapy in haematological malignancies.
AB  - The recent and rapid development of molecularly targeted therapy is best
      illustrated by advances in the management of haematological malignancy. In
      myeloid diseases we have seen dramatic improvements in the overall survival and
      quality of life for patients with chronic myeloid leukaemia treated with ABL and
      Src/ABL kinase inhibitors and we are poised to discover whether JAK2 inhibitors
      may offer similar benefit in myeloproliferative diseases. For acute myeloid
      leukaemia, the introduction of ATRA and myelotarg have had major impacts on the
      design of therapy regimens and many novel targeted agents, including farnesyl
      transferase, FLT3 and histone deacetylase inhibitors, are now in clinical trial.
      In lymphoid malignancies the highlight has been the introduction of rituximab,
      with significant improvements in the management of non-Hodgkin lymphoma and
      chronic lymphocytic leukaemia. The last 10 years has experienced a rapidly
      expanding interest and acceptance that leukaemic stem cells, including an
      improved ability to target them, may hold the key to improved response and
      reduced relapse rates across both myeloid and lymphoid disease. We now eagerly
      anticipate an era in which a wealth of preclinical discoveries are progressed to
      the clinic.

PMID- 20041452
TI  - Evaluation of the efficiency of the macrolactonization using MNBA in the
      synthesis of erythromycin A aglycon.
AB  - Various intermediates for the synthesis of erythronolide A, an aglycon of
      erythromycin A, are prepared from the corresponding seco-acids using 2-methyl-6
      nitrobenzoic anhydride (MNBA) in the presence of 4-(dimethylamino)pyridine (DMAP)
      with or without triethylamine. The efficiency of the MNBA lactonization is
      assessed by studying this method and comparing the results with those of the
      other established macrocyclization protocols. It has been finally concluded that
      (i) the conformationally appropriate substrate for the monomeric cyclization gave
      the desired lactone in excellent yield under mild reaction conditions in the
      presence of MNBA and DMAP, (ii) the highly-strained substrate for the cyclization
      also afforded the monomeric lactone in relatively good yield at 100 degrees C in
      toluene, and (iii) the seco-acid having stable linear conformation, which
      preferred dimerizing more than forming the monomeric lactone, provided the
      corresponding diolide in high yield with the constant ratio of the monomer to
      dimeric lactone (approximately 1/5).

PMID- 20041453
TI  - (1)H,(13)C and (19)F NMR data of N-substituted 6-(4-methoxyphenyl)-7H-pyrrolo[2,3
      d]pyrimidin-4-amines in DMSO-d(6).
AB  - Chemical shift assignment of seven N-substituted 6-(4-methoxyphenyl)-7H
      pyrrolo[2, 3-d]pyrimidin-4-amines, six of which are fluorinated, have been
      performed based on (1)H, (13)C, (19)F, and 2D COSY, HMBC and HSQC experiments.

PMID- 20041454
TI  - One-pot synthesis of diarylmethylidenefluorenes and phenanthrenes by palladium
      catalyzed multiple C-H bond functionalization.

PMID- 20041455
TI  - Multi-colour electroluminescence of dendronic antennae containing pyrenes as
      light harvesters.
AB  - Dendronic antennae systems containing pyrene units as energy donors and a
      styrylpyridinium derivative as energy acceptor show efficient energy transfer
      from the green-emitting pyrene excimer to the red-emitting acceptor. For the
      third dendron generation the effective screening of the pyrene units on the
      acceptor provides thin films showing bright red emission. Single-layer light
      emitting diodes prepared by properly balancing the dendrons and donor units
      concentration in polyvinylcarbazole show electroluminescence from the blue, green
      and red components of the monomeric donor, the donor excimer and the acceptor
      when excitons are generated in the polymer and subsequently transferred to the
      molecules by resonant energy transfer.

PMID- 20041456
TI  - Coupling interactions between sulfurous acid and the hydroperoxyl radical.
AB  - Radical-molecule complexes associated with the hydroperoxyl radical (HOO) play an
      important role in atmospheric chemistry. Herein, the nature of the coupling
      interactions between sulfurous acid (H(2)SO(3)) and the HOO radical is
      systematically investigated at the B3LYP/6-311++G(3df,3pd) level of theory in
      combination with the atoms in molecules (AIM) theory, the natural bond orbital
      (NBO) method, and energy decomposition analyses (EDA). Eight stable stationary
      points possessing double H-bonding features were located on the H(2)SO(3)...HOO
      potential energy surface. The largest binding energies of -12.27 and -11.72 kcal
      mol(-1) are observed for the two most stable complexes, where both of them
      possess strong double intermolecular H-bonds of partially covalence. Moreover,
      the characteristics of the IR spectra for the two most stable complexes are
      discussed to provide some help for their possible experimental identification.

PMID- 20041457
TI  - Tuned C-H functionalization to construct aza-podophyllotoxin/aza-conidendrin
      derivatives by means of domino cyclization.
AB  - An efficient domino cyclization method for the construction of aza
      podophyllotoxin/aza-conidendrin derivatives has been established. Reactions of
      different dienes with aryl halides in the presence of a palladium catalytic
      system produced different kinds of podophyllotoxin derivatives through a highly
      regioselective C-H functionalization. Treatment of dienes with aryl halides that
      have electron-withdrawing substituents on the phenyl ring created aza
      podophyllotoxin derivatives by means of the functionalization of the C-H bonds
      ortho to the C-halide bonds of the incoming aryl halides. The reaction of dienes
      with 1-iodobenzene or aryl halides that incorporate electron-donating groups
      produced aza-conidendrin derivatives by means of the functionalization of both
      sp(3) C-H and sp(2) C-H bonds. The regioselective C-H functionalization for the
      formation of different pseudo-podophyllotoxin/-conidendrin derivatives is proven
      by analyses of the (1)H NMR spectra of the products and selective X-ray analyses
      of the structures of the products. Thus, the palladium-catalyzed domino
      cyclization of 1,6-dienes for the preparation of aza-podophyllotoxin/aza
      conidendrin derivatives can be controlled by selectively controlling the C-H
      functionalization.

PMID- 20041458
TI  - Beyond traditional cross couplings: the scope of the cross dehydrogenative
      coupling reaction.
AB  - The development of new and environmentally compatible methods for the synthesis
      of C-C and C-heteroatom bonds is of great significance to researchers. The cross
      dehydrogenative coupling (CDC) is emerging as an important tool for chemists with
      a variety of, often inexpensive, metal catalysts able to perform these reactions
      both regio- and enantioselectively. Perhaps more importantly CDC methodology has
      been shown to be extremely environmentally friendly and facile being able to be
      carried out in aqueous environments under an atmosphere of air. This Focus Review
      intends to give an overview of the most contemporary developments in this
      exciting and emerging area of cross-coupling chemistry.

PMID- 20041459
TI  - Clinical chemistry: challenges for analytical chemistry and the nanosciences from
      medicine.
AB  - Clinical chemistry and laboratory medicine can look back over more than 150 years
      of eventful history. The subject encompasses all the medicinal disciplines as
      well as the remaining natural sciences. Clinical chemistry demonstrates how new
      insights from basic research in biochemical, biological, analytical chemical,
      engineering, and information technology can be transferred into the daily routine
      of medicine to improve diagnosis, therapeutic monitoring, and prevention. This
      Review begins with a presentation of the development of clinical chemistry.
      Individual steps between the drawing of blood and interpretation of laboratory
      data are then illustrated; here not only are pitfalls described, but so are
      quality control systems. The introduction of new methods and trends into
      medicinal analysis is explored, along with opportunities and problems associated
      with personalized medicine.

PMID- 20041460
TI  - Spin-state patterns in surface-grafted beads of iron(II) complexes.

PMID- 20041461
TI  - Direct polymerase synthesis of reactive aldehyde-functionalized DNA and its
      conjugation and staining with hydrazines.

PMID- 20041462
TI  - Saturnene revealed: X-ray crystal structure of D(5d)-C(60)F(20) formed in
      reactions of C(60) with A(x)MF(y) fluorinating agents (A=alkali metal; M=3d
      metal).

PMID- 20041463
TI  - Decarboxylative cross-coupling of aryl tosylates with aromatic carboxylate salts.

PMID- 20041464
TI  - Total synthesis of palau'amine.

PMID- 20041465
TI  - Three-dimensional vizualization of mouse brain by lipid analysis using ambient
      ionization mass spectrometry.

PMID- 20041466
TI  - Gold and organocatalysis combined.

PMID- 20041467
TI  - The role of chemistry in the energy challenge.
AB  - Chemistry with its key targets of providing materials and processes for
      conversion of matter is at the center stage of the energy challenge. Most energy
      conversion systems work on (bio)chemical energy carriers and require for their
      use suitable process and material solutions. The enormous scale of their
      application demands optimization beyond the incremental improvement of empirical
      discoveries. Knowledge-based systematic approaches are mandatory to arrive at
      scalable and sustainable solutions. Chemistry for energy, "ENERCHEM" contributes
      in many ways already today to the use of fossil energy carriers. Optimization of
      these processes exemplified by catalysis for fuels and chemicals production or by
      solid-state lightning can contribute in the near future substantially to the dual
      challenge of energy use and climate protection being in fact two sides of the
      same challenge. The paper focuses on the even greater role that ENERCHEM will
      have to play in the era of renewable energy systems where the storage of solar
      energy in chemical carries and batteries is a key requirement. A
      multidisciplinary and diversified approach is suggested to arrive at a stable and
      sustainable system of energy conversion processes. The timescales for
      transformation of the present energy scenario will be decades and the resources
      will be of global economic dimensions. ENERCHEM will have to provide the reliable
      basis for such technologies based on deep functional understanding.

PMID- 20041468
TI  - Confirmatory analysis for phase III population pharmacokinetics.
AB  - Population pharmacokinetics (POPPK) has many important uses at various stages of
      drug development and approval. At the phase III stage, one of the major uses of
      POPPK is to identify covariate influences on human pharmacokinetics, which is
      important for potential dose adjustment and drug labeling. One common analysis
      approach is nonlinear mixed-effect modeling, which typically involves time
      consuming extensive search for best fits among a large number of possible models.
      We propose that the analysis goal can be better achieved with a more standard
      confirmatory statistical analysis approach, which uses a prespecified primary
      analysis and additional sensitivity analyses. We illustrate this approach using a
      phase III study data set and compare the result with that calculated using the
      common exploratory approach. We argue that the confirmatory approach not only
      substantially reduces analysis time but also yields more accurate and
      interpretable results. Some aspects of this confirmatory approach may also be
      extended to data analysis in earlier stages of clinical drug development, i.e.
      phase II and phase I.

PMID- 20041469
TI  - Immunological detection of viral large T antigen identifies a subset of Merkel
      cell carcinoma tumors with higher viral abundance and better clinical outcome.

PMID- 20041470
TI  - Usefulness of species range polygons for predicting local primate occurrences in
      southeastern Peru.

PMID- 20041471
TI  - Effective primate conservation education: gaps and opportunities.
AB  - Conservation education goals generally include influencing people's conservation
      awareness, attitudes, and behaviors. Effective programs can help foster
      sustainable behavior, improve public support for conservation, reduce vandalism
      and poaching in protected areas, improve compliance with conservation
      regulations, increase recreation carrying capacities, and influence policies and
      decisions that affect the environment. Primate conservation problems cut across
      many disciplines, and primate conservation education must likewise address cross
      disciplinary issues. Conservation educators must incorporate both theoretical and
      practical knowledge and skills to develop effective programs, and the skill set
      must stretch beyond pedagogy. Expertise needed comes from the areas of planning,
      collaboration, psychology, entertainment, and evaluation. Integration of these
      elements can lead to greater program success.

PMID- 20041472
TI  - Missense polymorphisms in three oxidative-stress enzymes (GSTP1, SOD2, and GPX1)
      and dyskinesias in Russian psychiatric inpatients from Siberia.
AB  - Neuronal degeneration due to oxidative stress (OS) has been proposed as a
      mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms
      against OS may involve detoxification enzymes (e.g., glutathione peroxidase-1,
      GPX1; superoxide dismutase-2, SOD2 [also commonly known as MnSOD]; and
      glutathione S-transferase P1, GSTP1). Several pharmacogenetic studies have
      examined TD and OS in different ethnic groups, but not in Russians. Here we
      report the association between orofaciolingual (TDof) and limb-truncal
      dyskinesias (TDlt) and polymorphisms of GSTP1 (Ile105Val), MnSOD (Ala-9Val), and
      GPX1 (Pro197Leu) genes in 146 Russian inpatients from Siberia. We applied AIMS
      instrument to rate dyskinesias. Two-part model analyses, logistic and
      multivariate parametric regressions were applied to assess the effects of
      different variables (e.g., genotype, age, gender, and medication use). Our
      analyses do not suggest that Pro197Leu (GPX1) is associated with TD. However, our
      analyses suggest that the 105Val-allele of Ile105Val (GSTP1) may be associated
      with a lower risk and a severity of TDof and TDlt and that Ile105Val
      pharmacogenetics may be different in Slavonic Caucasians from that in American
      Caucasians. Furthermore, we find evidence for an association between Ala-9Val
      (MnSOD) and TDof, but not TDlt. Subject to further replication, our findings
      extend the available knowledge on the pharmacogenetics of TD and oxidative
      stress.

PMID- 20041473
TI  - Effect of metabolic blockade on the psychoactive effects of dextromethorphan.
AB  - OBJECTIVE: Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the
      pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls
      the production of dextrorphan, an active metabolite, with higher affinity for the
      NMDA receptor than the parent compound. This study examined whether
      pharmacological inhibition of CYP2D6 activity with quinidine would mimic the
      genetic mutation and thus also alter the psychoactive effects of DM. METHODS: In
      a single-blind, within-subjects study, eight healthy volunteers (all homozygous
      for the wild type allele for CYP2D6) received placebo and varying doses of DM,
      both with and without quinidine pre-treatment. Pharmacokinetic and
      pharmacodynamic measures were assessed at baseline and every hour post-drug for 6
      h. RESULTS: Compared to the no quinidine condition, quinidine pre-treatment
      decreased the area under the dose-response curve on subjective measures of
      positively reinforcing effects (e.g., euphoria, p < 0.04; drug liking, p < 0.05),
      and was significantly greater for measures of dysphoria (e.g., unpleasantness, p
      < 0.02). These changes corresponded to increased DM and decreased dextrorphan
      plasma concentrations. CONCLUSIONS: Compared to DM alone, quinidine pre-treatment
      inhibited DM metabolism and changed its subjective effects, demonstrating that
      the psychoactive properties of DM are a function of drug metabolism. These
      results demonstrate the relationship between CYP2D6 activity, plasma drug levels,
      and psychoactive drug effects, and have implications for both the abuse liability
      and therapeutic utility of DM.

PMID- 20041474
TI  - Switching stable patients with schizophrenia from depot and oral antipsychotics
      to long-acting injectable risperidone: reasons for switching and safety.
AB  - OBJECTIVE: An international, non-randomised study evaluated efficacy and safety
      of risperidone long-acting injectable (RLAI) compared to previous treatment. To
      investigate generizability of the European data set to the UK subset safety and
      switching data are reported here. METHODS: Patients with schizophrenia or other
      psychotic disorder, symptomatically stable on antipsychotic medication, received
      intramuscular injections of RLAI 25 mg (to a maximum of 50 mg) every 2 weeks for
      6 months. RESULTS: Of 182 UK patients enrolled, 79% had schizophrenia, 21% other
      psychotic disorders. Insufficient efficacy (43%), side effects (45%), and non
      compliance (25%) were the most common reasons for switching. Sixty-nine per cent
      of patients completed the trial; 8% discontinued due to adverse events (AEs).
      Most frequent treatment-emergent AEs were headache (8.2%), relapse (7.7%) and
      insomnia (7.1%); 8 (4.4%) patients reported injection-related AEs. There were
      significant improvements in extrapyramidal symptom rating scale total and
      subscale (particularly Parkinsonism) scores, regardless of previous medication
      (total cohort, p < or = 0.0001). There was a small but significant increase in
      body weight at endpoint (1.2 kg, p = 0.0023). One patient suffered a myocardial
      infarction and died (not treatment-related). There were no substantial
      differences between the full data set and the UK sub-population CONCLUSION:
      Switch to RLAI was well-tolerated in stable patients over 6 months. The European
      data set is generalizable to the UK patient population.

PMID- 20041475
TI  - Lorazepam modulates orbitofrontal signal changes during emotional processing in
      catatonia.
AB  - OBJECTIVE: Catatonia is a psychomotor syndrome characterized by concomitant
      emotional, behavioural and motor symptoms. In many cases clinical symptoms
      disappear almost immediately with administration of lorazepam, which acts on
      GABA(A) receptors. METHODS: Using functional magnetic resonance imaging (fMRI) we
      investigated prefrontal activation patterns during emotion processing in
      catatonic patients with and without lorazepam in a double-blind study design. For
      emotional stimulation the International Affective Picture System (IAPS) was used.
      BOLD-signals were determined using regions of interest (ROI) and were
      statistically compared between groups. RESULTS: For negative emotional pictures
      lorazepam induced higher signal decreases in the orbitofrontal cortex (OFC) in
      catatonic patients than in healthy subjects resulting in a regularization of
      activity patterns comparable to healthy subjects with placebo. CONCLUSIONS:
      Results indicate disturbances in the functioning of OFC in catatonia. GABAergic
      modified emotion regulation with decreased inhibition of affective stimuli could
      lead to the intense emotions reported by many catatonic patients.

PMID- 20041476
TI  - Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: a
      comprehensive review of their clinical efficacy.
AB  - Anxiety disorders are common psychiatric conditions that typically require long
      term treatment. This review summarizes current knowledge of the pharmacological
      treatment of anxiety disorders with serotonin norepinephrine reuptake inhibitors
      (SNRIs) with specific emphasis on the findings of recent randomized clinical
      trials and relevant neurobiological investigations. It is now well established
      that gabaergic, noradrenergic and serotonergic systems play a critical role in
      the pathophysiology of anxiety disorders, abnormalities in these systems being
      related to structural and functional alterations in specific brain areas such as
      the amygdala, prefrontal cortex, locus coeruleus and hippocampus, as repeatedly
      shown by neuroimaging studies. SNRIs selectively inhibit norepinephrine and
      serotonin reuptake and have shown to be efficacious and generally well tolerated
      treatments in patients with anxiety disorders, with some potential clinical
      advantages over selective serotonin reuptake inhibitors (SSRIs), which are
      considered by many to represent first-line pharmacological treatments in patients
      with anxiety disorders. Anxiety disorders are characterized by a typically
      chronic course, high rates of comorbidity and frequent partial response to
      standard treatments, and the increasing use of SNRIs reflects currently unmet
      clinical need, in terms of overall response, remission rates and treatment
      tolerability.

PMID- 20041477
TI  - Alterations in cortical activity of male methamphetamine abusers performing an
      empathy task: fMRI study.
AB  - OBJECTIVES: We investigate possible differences in neural correlates of empathy
      processing between abstinent methamphetamine (MA) abusers and healthy subjects
      using functional magnetic resonance imaging (fMRI). METHODS: Nineteen abstinent
      MA abusers (mean age of 36.06 years, range 31-52 years) and 19 healthy subjects
      (mean age of 37.05 years, range 33-42 years) participated in this study. A visual
      fMRI activation paradigm was used, comprising a series of cartoons, each
      depicting a short story. There were two categories of stories: empathy (Empathy)
      and Physical causality (Physical). fMRI images were acquired using a 3.0 T whole
      body scanner. All fMRI data were analyzed using MATLAB v. 7.2 and SPM5. RESULTS:
      Both MA subjects and controls exhibited activation in the dorsomedial prefrontal
      cortex. Despite this similarity in activation patterns, we found that the two
      groups differed in the activation of several cortical regions associated with the
      processing of empathy information. Hypoactivations of the orbitofrontal cortex,
      temporal poles, and hippocampus in MA abusers relative to healthy subjects
      suggests that the ability of empathic response could be compromised in abstinent
      MA abusers (p < 0.05, corrected for a small volume). CONCLUSIONS: Functional
      impairments in the empathic neural network caused by MA may contribute to the
      misunderstanding of others and to the erosion of social interactions in MA
      abusers.

PMID- 20041478
TI  - Enhancing medication adherence in patients with bipolar disorder.
AB  - OBJECTIVES: Medication adherence contributes to the efficacy-effectiveness gap of
      treatment in patients with bipolar disorder. This paper aims to examine the
      challenges involved in improving medication adherence in bipolar disorder, and to
      extract some suggestions for future directions from the core psychosocial studies
      that have targeted adherence as a primary or secondary outcome. METHODS: A search
      was conducted for articles that focused on medication adherence in bipolar
      disorder, with emphasis on publications from 1996 to 2008 using Medline, Web of
      Science, CINAHL PLUS, and PsychINFO. The following key words were used:
      adherence, compliance, alliance, adherence assessment, adherence measurement,
      risk factors, psychosocial interventions, and psycho-education. RESULTS: There
      are a number of challenges to understanding non-adherence including the
      difficulty in defining and measuring it and the various risk factors that need to
      be considered when aiming to enhance adherence. Nevertheless, the importance of
      addressing adherence is evidenced by the connection between adherence problems
      and poor outcome. Despite these challenges, a number of small psychosocial
      studies targeting adherence as a primary outcome point to the potential
      usefulness of psycho-education aimed at improving knowledge, attitudes, and
      adherence behavior, but more large scale randomized controlled trials are needed
      in this area. Evidence of improved outcomes from larger randomized controlled
      trials of psychosocial interventions that target medication adherence as a
      secondary outcome suggests that tackling other factors besides medication
      adherence may also be an advantage. While some of these larger studies
      demonstrate an improvement in medication adherence, the translation of these
      interventions into real life settings may not always be practical. A person
      centered approach that considers risk factors for non-adherence and barriers to
      other health behaviors may assist with the development of more targeted briefer
      interventions. Integral to improving medication adherence is the delivery of
      psycho-education, and attention needs to be paid to the implementation, and
      timing of psycho-education. Progress in the understanding of how medicines work
      may add to the credibility of psycho-education in the future. CONCLUSIONS:
      Enhancement of treatment adherence in bipolar patients is a necessary and
      promising management component as an adjunct to pharmacotherapy. The current
      literature on psychosocial interventions that target medication adherence in
      bipolar disorder points to the possibility of refining the concept of non
      adherence and adapting psycho-education to the needs of certain subgroups of
      people with bipolar disorder. Large scale randomized controlled trials of briefer
      or more condensed interventions are needed that can inform clinical practice.

PMID- 20041479
TI  - Proliferation of green Paramecium bursaria: a vision through flow cytometry.

PMID- 20041480
TI  - Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with
      prognosis, endometrial thickness, or bone mineral density in Japanese breast
      cancer patients treated with adjuvant tamoxifen.

PMID- 20041481
TI  - Long-term quality of life after radiotherapy for the treatment of anal cancer.
AB  - BACKGROUND: Radiotherapy is the current standard of care for patients with
      localized squamous cell cancer of the anal canal. The goal of the current study
      was to evaluate long-term quality of life (QoL) in patients after this treatment.
      METHODS: Questionnaires were mailed to 80 patients treated with definitive
      radiotherapy, with or without concurrent chemotherapy, for anal cancer, with a
      minimum 2-year interval after the completion of radiotherapy. The questionnaire
      included the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), the
      Medical Outcomes Study (MOS) Sexual Problems Scale, and questions regarding
      demographic characteristics and comorbidities. RESULTS: A total of 32 (40%)
      patients completed the questionnaire. There were no significant differences noted
      with regard to clinical and demographic characteristics between the survey
      responders and nonresponders. Among the 32 responders, the median dose of
      radiotherapy was 55 Grays (Gy), and 97% had received concurrent chemotherapy. The
      median interval between radiotherapy and survey participation was 5 years (range,
      3-13 years). The median total FACT-C score was 108 (range, 47-128), of a maximum
      (best possible) score of 136. Patients who reported depression or anxiety and
      younger patients were found to have significantly lower total FACT-C scores. The
      median scores on the Physical, Social/Family, Emotional, Functional, and
      Colorectal subscales of the FACT-C were 20, 23, 21, 22, and 21, respectively, of
      maximum (best possible) scores of 28, 28, 24, 28, and 28, respectively. The
      median score on the MOS Sexual Problems Scale was 67 (range, 0-100), of a maximum
      (worst possible) score of 100. CONCLUSIONS: Patients treated with radiotherapy
      for anal cancer reported acceptable overall QoL scores, but poor sexual function
      scores. Investigations are warranted into more modern radiation techniques that
      could potentially reduce late toxicity from radiotherapy.

PMID- 20041482
TI  - Correlation of pretransplant and early post-transplant response assessment with
      outcomes after reduced-intensity allogeneic hematopoietic stem cell
      transplantation for non-Hodgkin's lymphoma.
AB  - BACKGROUND: Chemotherapy sensitivity, defined simply as at least a partial
      response to chemotherapy, is an important outcome predictor for non-Hodgkin
      lymphoma (NHL) patients undergoing reduced-intensity allogeneic hematopoietic
      stem cell transplantation (allo-HCT). The authors hypothesized that further
      differentiation of chemotherapy sensitivity by specific response, complete
      remission (CR) versus partial remission (PR) versus stable disease (SD) versus
      progression of disease (PD), correlates with post-transplant outcomes. METHODS:
      The impact of pretransplant and early (28 days) post-transplant disease response
      on transplant outcomes was analyzed in 63 NHL patients treated with reduced
      intensity allo-HCT. RESULTS: The 3-year event-free survival (EFS) and overall
      survival (OS) (median potential follow-up after reduced-intensity allo-HCT = 58
      months) for all patients was 37% and 47%, respectively. The 3-year EFS based on
      pretransplant response was: CR = 50%; PR = 66%; SD = 18%; no patient with PD
      pretransplant reached 3-year follow-up. The 3-year OS based on pretransplant
      response was: CR = 63%; PR = 69%; SD = 45%. The 3-year EFS based on post
      transplant response was: CR = 57%; PR = 32%; SD = 33%; no patient with PD post
      transplant reached 3-year follow-up. The 3-year OS based on post-transplant
      response was: CR = 65%; PR = 43%; SD = 50%. In multivariate analyses,
      pretransplant response was the best predictor of EFS (P < .0001). Pretransplant
      response (P < .0001) and age (P = .0035) were jointly associated with OS.
      CONCLUSIONS: These data suggest that NHL patients with pretransplant SD,
      generally considered inappropriate candidates, may benefit from reduced-intensity
      allo-HCT, and patients with pretransplant PD should only receive this therapy in
      clinical trials.

PMID- 20041483
TI  - Serum amyloid A: a novel biomarker for endometrial cancer.
AB  - BACKGROUND: The authors investigated the expression of serum amyloid A (SAA) in
      endometrial endometrioid carcinoma and evaluated its potential as a serum
      biomarker. METHODS: SAA gene and protein expression levels were evaluated in
      endometrial endometrioid carcinoma and normal endometrial tissues, by real-time
      polymerase chain reaction (PCR), immunohistochemistry (IHC), and flow cytometry.
      SAA concentration in 194 serum samples from 50 healthy women, 42 women with
      benign diseases, and 102 patients including 49 grade 1, 38 grade 2, and 15 grade
      3 endometrial endometrioid carcinoma was also studied by a sensitive bead-based
      immunoassay. RESULTS: SAA gene expression levels were significantly higher in
      endometrial endometrioid carcinoma when compared with normal endometrial tissues
      (mean copy number by real-time PCR = 182 vs 1.9; P = .001). IHC revealed diffuse
      cytoplasmic SAA protein staining in poorly differentiated endometrial
      endometrioid carcinoma tissues. High intracellular levels of SAA were identified
      in primary endometrial endometrioid carcinoma cell lines evaluated by flow
      cytometry, and SAA was found to be actively secreted in vitro. SAA concentrations
      (microg/mL) had medians of 6.0 in normal healthy women and 6.0 in patients with
      benign disease (P = .92). In contrast, SAA values in the serum of endometrial
      endometrioid carcinoma patients had a median of 23.7, significantly higher than
      those of the healthy group (P = .001) and benign group (P = .001). Patients
      harboring G3 endometrial endometrioid carcinoma were found to have SAA
      concentrations significantly higher than those of G1/G2 patients. CONCLUSIONS:
      SAA is not only a liver-secreted protein, but is also an endometrial endometrioid
      carcinoma cell product. SAA is expressed and actively secreted by G3 endometrial
      endometrioid carcinoma, and it is present in high concentration in the serum of
      endometrial endometrioid carcinoma patients. SAA may represent a novel biomarker
      for endometrial endometrioid carcinoma to monitor disease recurrence and response
      to therapy.

PMID- 20041484
TI  - Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter
      American College of Radiology Imaging Network trial.
AB  - BACKGROUND: The study was conducted to determine whether radiofrequency ablation
      (RFA) can safely reduce pain from osseous metastatic disease. METHODS: The single
      arm prospective trial included patients with a single painful bone metastasis
      with unremitting pain with a score >50 on a pain scale of 0-100. Percutaneous
      computed tomography-guided RFA of the bone metastasis to temperatures >60 degrees
      C was performed. Endpoints were the toxicity and pain effects of RFA before and
      at 2 weeks, 1 month, and 3 months after RFA. RESULTS: Fifty-five patients
      completed RFA. Grade 3 toxicities occurred in 3 of 55 (5%) patients. RFA reduced
      pain at 1 and 3 months for all pain assessment measures. The average increase in
      pain relief from pre-RFA to 1-month follow-up is 26.3 (95% confidence interval
      [CI], 17.7-34.9; P < .0001), and the increase from pre-RFA to 3-month follow-up
      is 16.38 (95% CI, 3.4-29.4; P = .02). The average decrease in pain intensity from
      pre-RFA to 1-month follow-up was 26.9 (P < .0001) and 14.2 for 3-month follow-up
      (P = .02). The odds of lower pain severity at 1-month follow-up were 14.0 (95%
      CI, 2.3-25.7; P < .0001) times higher than at pre-RFA, and the odds at 3-month
      follow-up were 8.0 (95% CI, 0.9-15.2; P < .001) times higher than at pre-RFA. The
      average increase in mood from pre-RFA to 1-month follow-up was 19.9 (P < .0001)
      and 14.9 to 3-month follow-up (P = .005). CONCLUSIONS: This cooperative group
      trial strongly suggests that RFA can safely palliate pain from bone metastases.

PMID- 20041485
TI  - Knowledge of hepatitis C virus screening in long-term pediatric cancer survivors:
      a report from the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Pediatric cancer survivors who were treated before routine hepatitis
      C virus (HCV) screening of blood donors in 1992 have an elevated risk of
      transfusion-acquired HCV. METHODS: To assess long-term pediatric cancer
      survivors' knowledge of HCV testing and blood transfusion history, a
      questionnaire was administered to 9242 participants in the Childhood Cancer
      Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy
      from 1970 to 1986. RESULTS: More than 70% of survivors reported either no prior
      HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting
      prior testing. One half recalled having a treatment-related blood transfusion;
      those who recalled a transfusion were more likely to report HCV testing (39%)
      than those who did not (18%) or were unsure (20%). In multivariate models,
      survivors who reported no prior HCV testing were more likely to be older (odds
      ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and
      to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI,
      1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no
      transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR,
      2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9;
      95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5
      1.0). CONCLUSIONS: Many pediatric cancer survivors at risk for transfusion
      acquired HCV are unaware of their transfusion history and prior testing for HCV
      and would benefit from programs to increase HCV knowledge and screening.

PMID- 20041486
TI  - Ovarian metastases from breast cancer: report of 29 cases.
AB  - BACKGROUND: The objective of this study was to describe the characteristics and
      survival outcomes of patients with breast cancer who had ovarian metastases.
      METHODS: Data from 29 women who underwent surgery were reviewed retrospectively
      (from 1998 to 2007). Patient characteristics, tumor characteristics, and
      treatment data were collected. Pelvic extent of disease was documented using a
      system analogous to the International Federation of Gynecology and Obstetrics
      classification for ovarian cancer. Global survival, disease-free intervals, and
      the distribution to other metastatic sites over time were studied. Outcomes were
      compared between the group who underwent macroscopic resection of lesions and the
      group who did not undergo resection. RESULTS: The data indicated a predominance
      of premenopausal and hormone receptor-positive status and a greater prevalence of
      lobular infiltrating carcinoma, bilateral breast cancer, and predisposing genetic
      factors compared with the global population with breast cancer. Ovarian disease
      was diagnosed at a median of 5 years after breast cancer. Seventy-five percent of
      patients were asymptomatic, and advanced-stage pelvic extent or extra-abdominal
      metastases were observed in 41.5% of patients. The median survival was 3 years,
      and the median follow-up was 2 years. Survival improved significantly when
      optimal debulking surgery was performed. CONCLUSIONS: Breast cancers may be
      associated with ovarian metastases. The current results indicated that surgical
      resection tends to increase survival, which may be long; however, larger series
      would be needed to confirm other prognostic factors. The high rates of hormone
      receptor-positive tumors and premenopausal patients led the authors to suggest
      that the surgical option should consist of at least bilateral oophorectomy, even
      when the contralateral ovary appears to be normal.

PMID- 20041487
TI  - An in-situ fluorescence-based optical extensometry system for imaging
      mechanically loaded bone.
AB  - The application and quantification of well-controlled tissue strains is required
      for investigations into mechanisms of tissue adaptation within the
      musculoskeletal system. Although many commercial and custom extensometry systems
      exist for large biological samples, integrated loading/strain measurement for
      small samples is not as readily available. Advanced imaging modules such as laser
      scanning microscopy provide in situ, minimally invasive tools to probe cellular
      and molecular processes with high spatiotemporal resolution. Currently, a need
      exists to devise loading/strain measurement systems that can be integrated with
      such advanced imaging modules. We describe the development and validation of a
      fluorescence-based, optical extensometry system directly integrated within a
      confocal microscopy platform. This system allows in situ measurement of surface
      strain and is compatible with the direct imaging of cellular processes within
      small bone samples. This optical extensometry system can accurately and
      reproducibly measure physiologically relevant surface strains (200 to 3000
      microstrain) in beams machined from various well-characterized materials,
      including bovine femoral cortex, and in intact murine tibia. This simple system
      provides a powerful tool to further our investigation of the relationships
      between mechanical loading, fluid and solute transport, and mechanosensation
      within the musculoskeletal system.

PMID- 20041488
TI  - Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA
      1 in Met expression.
AB  - Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer
      may have important diagnostic, prognostic, and therapeutic value, but there is no
      data on miRNA expression in chordoma. The purpose of this study was to identify
      the role of miRNAs in human chordoma. We analyzed miRNA expression in chordoma
      derived cell lines and chordoma tissue by using miRNA microarray technology with
      unsupervised hierarchical clustering analysis. The relative expression levels of
      these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot
      analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably
      transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted
      gene Met in chordoma tissues was also studied. We observe that human chordoma
      tissues and cell lines can be distinguished from normal muscle tissue by
      comparing miRNA expression profiles. Several miRNAs were differentially expressed
      in chordoma cell lines compared to controls, and similar expression patterns were
      found in primary chordoma tissues. Importantly, we were able to show for the
      first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two
      miRNAs implicated in a number of other cancer types, were markedly decreased in
      both chordoma tissues and cell lines. When chordoma cell lines were transfected
      with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets
      included Met and HDAC4-two genes that were observed to be overexpressed in
      chordoma. Our results demonstrate that some miRNAs are differentially expressed
      in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma
      tumor pathogenesis.

PMID- 20041489
TI  - Myosin heavy chain isoform profiles remain altered at 7 months if the lacerated
      medial gastrocnemius is poorly reinnervated: a study in rabbits.
AB  - Lacerated skeletal muscles often do not recover full function after repair.
      Denervated muscles with altered myosin heavy chain isoform (MHC) profiles are
      known to result in functional impairment. We studied the functional recovery of
      lacerated muscles, assessing MHC profile changes in association to the
      involvement of the intramuscular nerve (IM). We tested three lacerated models
      using the rabbit's medial gastrocnemius where the IM was either cut (NNR),
      repaired (NR), or preserved intact (NP). Muscles were assessed 7 months after
      repair for muscle atrophy, isometric contraction (by electrical stimulation), and
      fibrosis formation at the lesion site. Changes in myofibrillar actomyosin
      adenosine triphosphatase activity, MHC profile, regenerating myofibers and
      reinnervation were assessed by Western blot, histology, or immunohistology.
      Lacerated muscles with a repaired (NR) or an intact (NP) IM showed good recovery,
      with no significant changes in the MHC profile. Muscles where the IM was not
      repaired (NNR) resulted in significant scar area at the lesion site (p < 0.05),
      muscle atrophy (67%, p < 0.05) and loss in contractile properties (63% of the
      uninjured side, p < 0.05). At 7 months, all muscles were reinnervated. However,
      the NNR had an inappropriate (polyneural) and poorly distributed reinnervation,
      the presence of regenerating myofibers, and demonstrated a fast-to-slow MHC
      transition (71%:29% to 44%:56%, ANOVA, p = 0.018). This was associated to the cut
      IM when the NNR muscle was lacerated. Poor reinnervation in lacerated skeletal
      muscles alters the myosin heavy chain profile permanently. This study provides a
      rationale to also consider biological solutions to improve nerve regeneration and
      reinnervation in the surgical repair of lacerated muscles.

PMID- 20041490
TI  - Action of IL-1beta during fracture healing.
AB  - After bone injury, developmental processes such as endochondral and
      intramembranous ossification are recapitulated as the skeleton regenerates. In
      contrast to development, skeletal healing involves inflammation. During the early
      stages of healing a variety of inflammatory cells infiltrate the injured site,
      debride the wound, and stimulate the repair process. Little is known about the
      inflammatory process during bone repair. In this work, we examined the effect of
      a pro-inflammatory cytokine, Interleukin-1 beta (IL-1beta), on osteoblast and
      stem cell differentiation and on intramembranous and endochondral ossification,
      because IL-1beta exerts effects on skeletal homeostasis and is upregulated in
      response to fracture. We determined that IL-1beta stimulated proliferation of
      osteoblasts and production of mineralized bone matrix, but suppressed
      proliferation and inhibited differentiation of bone marrow derived MSCs. We next
      performed loss- and gain-of-function experiments to determine if altering IL
      1beta signaling affects fracture healing. We did not detect any differences in
      callus, cartilage, and bone matrix production during healing of nonstabilized or
      stabilized fractures in mice that lacked the IL-1beta receptor compared to wild
      type animals. We observed subtle alterations in the healing process after
      administering IL-1beta during the early phases of repair. At day 10 after injury,
      the ratio of cartilage to callus was increased, and by day 14, the proportion of
      cartilage to total callus and to bone was reduced. These changes could reflect a
      slight acceleration of endochondral ossification, or direct effects on cartilage
      and bone formation.

PMID- 20041491
TI  - Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4)
      and death receptor 5 (DR5) in human osteosarcoma cells.
AB  - Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma
      (OS), satisfactory results are still difficult to achieve. Novel therapeutic
      modalities need to be developed for osteosarcoma treatment. The combined effects
      of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and ionizing
      radiation (IR) on human OS cells were investigated. IR and TRAIL treatment
      synergistically decreased the cell viability and enhanced apoptosis in OS cell
      lines. IR pretreatment enhances TRAIL-induced Bid and caspase-3 activations.
      Decreases in the expression levels of the antiapoptotic proteins c-FLIP and XIAP
      also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced
      DR4 and DR5 expressions at the transcription stage. These results can become the
      basic lines of evidence for the future treatment of OS using TRAIL with IR.

PMID- 20041492
TI  - Chondrogenic differentiation of human subchondral progenitor cells is impaired by
      rheumatoid arthritis synovial fluid.
AB  - In microfracture, subchondral progenitors enter the cartilage defect and form
      cartilage repair tissue. We hypothesize that synovial fluid (SF) from rheumatoid
      arthritis (RA) donors affects chondrogenesis of human subchondral progenitors
      stimulated with transforming growth factor-beta3 (TGFB3), whereas SF from normal
      and osteoarthritis (OA) donors do not. Human progenitors from subchondral cortico
      spongious bone (pool of n = 4) were cultured in micromasses under serum-free
      conditions and were stimulated with 10 ng/mL TGFB3 and with 5% SF from normal,
      OA, and RA donors (pool of n = 7, each). Histological staining of proteoglycan
      and immunostaining of type II collagen showed that progenitors stimulated with SF
      from RA donors show significantly reduced cartilage matrix formation compared to
      progenitors treated with TGFB3 or with SF from normal and OA donors (n = 3,
      each). Gene expression analysis of typical chondrocyte marker genes and genes
      encoding matrix modifying enzymes showed that SF from OA and RA donors influence
      the onset of TGFB3-mediated chondrogenesis (pool of 20 micromasses), but had no
      effect on the gene expression profile after prolonged culture in micromasses.
      These results suggest that SF from RA patients may impair the chondrogenic
      development of mesenchymal progenitors in microfracture, whereas osteoarthritic
      SF may has no negative effect on the cartilage matrix formation.

PMID- 20041493
TI  - Early lifestage exposure and potential developmental susceptibility to
      tetrachloroethylene.
AB  - BACKGROUND: Tetrachloroethylene, also known as perchloroethylene or "perc", is a
      highly volatile and lipophilic solvent widely used in dry cleaning, textile
      processing, and metal-cleaning operations. The limited epidemiological and
      toxicological data available for exposure to perc during developmental
      lifestages, as well as the evidence for critical windows of exposure, highlight
      early life as a period of potential susceptibility. METHODS: A literature search
      was performed to identify all peer-reviewed epidemiological and toxicologial
      studies examining outcomes from early lifestage exposure to perc, and reviewed by
      developmental stage for both exposure and outcome. RESULTS: Exposure scenarios to
      perc unique to early lifestages include transplacental and breast milk intake,
      along with inhalation, ingestion, or dermal exposure. Toxicokinetics factors that
      may influence early lifestage susceptibility to perc, along with existing
      physiologically based pharmacokinetic (PBPK) models, are described. Adverse
      outcomes examined include: reproductive outcomes examined prior to conception
      including reduced fertility, adverse effects on sperm, or altered reproductive
      hormones; prenatal outcomes examined after exposure prior to conception or
      prenatally including fetal death, birth defects, and decreased birth weight;
      postnatal outcomes examined after exposure prior to conception, prenatally, or
      during childhood including neurotoxicity, immunotoxicity, cancer, hepatotoxicity,
      congential anomalies and mortality; and adult schizophrenia examined after
      exposure prior to conception. CONCLUSIONS: The limited evidence on early
      lifestage exposure to perc does not provide sufficient evidence of this sensitive
      period as being more or less important than exposure at a later lifestage, such
      as during adulthood. However, there are a number of adverse health effects
      observed uniquely in early lifestages, and increased sensitivity to visual system
      deficits is suggested in children. Other outcomes observed in adults may not have
      been adequately assessed in children to directly compare sensitivity.

PMID- 20041494
TI  - Global media events in India: contests over beauty, gender and nation.

PMID- 20041495
TI  - Some haphazard aphorisms for epidemiology and life.

PMID- 20041496
TI  - [The emergency medical relief system during the Sino-Japanese War: the medical
      relief corps of the Chinese Red Cross in particular].

PMID- 20041497
TI  - Chronic disease or chronic diseases:  is the whole different from the sum of the
      parts?

PMID- 20041498
TI  - From "tact" in Ferenczi to "resonance" in Nicolas Abraham.

PMID- 20041499
TI  - Between memory and desire: from history to psychoanalysis and back.

PMID- 20041500
TI  - Freud, Stekel and the interpretation of dreams: the affinities with existential
      analysis.

PMID- 20041501
TI  - Jeno Varga, the Hungarian Soviet Republic and the development of psychoanalysis
      in the Soviet Union.

PMID- 20041502
TI  - Freud and Jewish dreaming.

PMID- 20041503
TI  - Notes on a controversy: the question of lay analysis.

PMID- 20041504
TI  - [Cavinton in the treatment of cochleovestibular disorders of vascular genesis].

PMID- 20041505
TI  - [Chronic adenoiditis prevention in children with acid-depended stomach
      pathology].

PMID- 20041506
TI  - [Nasopharyngeal teratoma].

PMID- 20041507
TI  - [Febrile conditions in otorhinolaryngology].

PMID- 20041508
TI  - [On certain topical problems of otorhinolaryngology].

PMID- 20041509
TI  - [Programmed staged surgical treatment of polytrauma].

PMID- 20041510
TI  - [Another approach to the Fournier disease in surgical practice].

PMID- 20041511
TI  - [Improvement of surgical training].

PMID- 20041512
TI  - [A case of the disseminated splenosis after splenectomy].

PMID- 20041513
TI  - [Acute occlusion of superior mesenteric artery].

PMID- 20041514
TI  - [Cardio-vascular complications risk assessment by non-cardiac surgical
      operations].

PMID- 20041515
TI  - [The Tietze syndrome].

PMID- 20041516
TI  - [Primary rhinocheiloplasty in comprehensive treatment of children with congenital
      one-sided cleft of upper lip and alveolar process].

PMID- 20041517
TI  - [Implementation of military-medical technologies into surgical service].

PMID- 20041518
TI  - [Sociological study of dental fluorisis].

PMID- 20041519
TI  - [The use of current bandages in the treatment of patients with venous trophic
      ulcers of the skin: clinical and economic aspects].

PMID- 20041520
TI  - [CO(2)-laser in treatment of patients with basal cell face cancer].

PMID- 20041521
TI  - Who's next? Succession planning paves a path to your organization's future.

PMID- 20041522
TI  - [Comparative analysis of Lichtenstein hernioplasty and plasty with prolene
      herniosystem (PHS)].

PMID- 20041523
TI  - [Stomatological status changes in patients with sharp dysentery and
      salmonellosis].

PMID- 20041524
TI  - CE-IT integration from the IT perspective.

PMID- 20041525
TI  - Starting, developing and growing a medical device company.

PMID- 20041526
TI  - Develping a career ladder.

PMID- 20041527
TI  - Speeding up a slow steam generator.

PMID- 20041528
TI  - 'Know your customer' lunches build relationships, goodwill.

PMID- 20041529
TI  - How can you pass the exam? Listen to those who know...

PMID- 20041530
TI  - Biomeds, manufacturers play pivotal roles in infection prevention.

PMID- 20041531
TI  - Sleep studies.

PMID- 20041532
TI  - Auto-provisioning of biomedical devices on a converged IP network.

PMID- 20041533
TI  - A comprehensive X-ray machine inspection program.

PMID- 20041534
TI  - Guidelines for planning and hosting a successful FDA medical device inspection.

PMID- 20041535
TI  - Revisiting To Err Is Human a decade later.

PMID- 20041536
TI  - Hospitals must account for vendors' work.

PMID- 20041538
TI  - Pilot project aims to ease standards comparisons.

PMID- 20041537
TI  - Practical guidance on ST79--what's new in steam sterilization?

PMID- 20041539
TI  - Communication interface and graphic module for audiometry equipment.
AB  - The National Rehabilitation Institute (INR) in Mexico City purchased 12 Madsen
      Orbiter 922 audiometers in 2006. While this audiometer is excellent for
      diagnosing the degree and type of hearing loss, it has presented problems in
      transfering, saving and printing the results of special tests and logoaudiometry
      from audiometer to workstation with the NOAH-3 system. The data are lost when the
      audiometer is turned off or a new patient is captured. There is no database
      storing and, shortly after the results have been printed on the thermal paper,
      the audiograms are erased. This problem was addressed by designing and
      implementing the InterAudio (AAMS) communication and graphical interface. The
      limitations and scope of the Automatic Audiometric Measurement System were
      analyzed, then a search of technical information was performed that included the
      resources for designing, developing and implementing the transfer interface, the
      user's graphical module requirements, and the tools for printing and saving the
      study.

PMID- 20041540
TI  - Sterilization of products contaminated with Pyronema domesticum.
AB  - Product recalls due to non-sterility occurred between 1993 and 1994 among
      manufacturers that were sterilizing cotton products sourced from China using
      ethylene oxide (EO). The primary contaminant was identified as a pyrophilous mold
      from the class Discomycetes, Pyronema domesticum. Multiple references suggest
      this organism has special needs for reproducing and maintaining the two assumed
      resistant stages of this organism (ascospores and sclerotia). Sterilization
      resistance studies were performed using a China-sourced cotton product that was
      naturally contaminated with P. domesticum. These studies showed the organisms to
      have: 1) a low resistance to moist heat sterilization at 250 degrees F (121
      degrees C); a resistance to radiation no greater than that predicted by the
      bioburden-based resistance model (i.e., Population C) used for dose determination
      Method 1 described in ANSI/AAMI/ISO 11137-2:2006--Sterilization of health care
      products--Radiation--Part 2: Establishing the sterilization dose; and 3) a high
      resistance to EO processing.

PMID- 20041541
TI  - Manufacturer recommended PM intervals: is it time for a change?

PMID- 20041542
TI  - [Latest therapeutic techniques applied to the otorhinolaryngological and head and
      neck regions: the head and neck area].

PMID- 20041543
TI  - [Surgical treatment of vertigo].

PMID- 20041544
TI  - [Revision of the law concerning public health nurses, midwives and nurses and an
      overview of public health nursing education (2). A course on community nursing
      necessary for the program of nursing education and the community health course
      needed for the program for public health nursing--the educational content of the
      former and a suggestion for the law specific for nurses].

PMID- 20041545
TI  - [The way of women. Suzanne Bourret, fighter for the soul].

PMID- 20041546
TI  - [Journal at the virtual edge. Electronic portfolio at the University of Moncton].

PMID- 20041547
TI  - [Beds in the age of sun and cancer. Suffering to be beautiful? Not to the point
      of delivering one's skin to ultraviolet rays].

PMID- 20041548
TI  - [Therapeutic honey].

PMID- 20041549
TI  - [Denise St-Cyr Tribble: a career consecrated to the advancement of psychiatric
      nurses].

PMID- 20041550
TI  - [Drug addiction: at the Dollard-Cormier Center, nurses at the heart of the
      combat].

PMID- 20041551
TI  - [Screening for infectious diseases. At Seven Islands, a protocol for prevention
      facilitates the necessary steps for nurses].

PMID- 20041552
TI  - [Breast cancer. Pivotal roles for nurses, oncologic nurses or nurses in research,
      three nursing interventions].

PMID- 20041553
TI  - [Baby tears. Do they hide serious problems? A study of infants unleashes the
      urgency that causes excessive tears].

PMID- 20041554
TI  - [Seat for the child. Until the child is 4 years old, it is better to arrange his
      safety seat in the back of the vehicle].

PMID- 20041555
TI  - [Role of parents in the neonatal unit. Nursing interventions regarding the
      development of feelings of attachment and parental competence].

PMID- 20041556
TI  - [Orthostatic hypotension. Nursing evaluation and interventions].

PMID- 20041557
TI  - [Delirium in the intensive care unit. medication--an underestimated risk factor].

PMID- 20041558
TI  - [The VIP project].

PMID- 20041559
TI  - [Jurisdiction in health. Beyond the financial situation].

PMID- 20041560
TI  - Mitral valve inserted backward-pt. dies: court upholds dismissal. Vivas v.
      Regents of University of California, A 121679 (10/30/2009)-CA.

PMID- 20041561
TI  - Employee manuals may give rights to 'at-will' employees. Case on point: Fennessey
      v. Mt. Carmel Health Sys., Inc., 2009-Ohio-3750 (7/30/2009)-OH.

PMID- 20041562
TI  - FL: RN with hepatitis C wins workers comp.: court held last exposure rule did not
      apply. Fidelity and Guaranty Ins. Co. V. Polk County, 2D08-3377 (8/14/2009)-FL.

PMID- 20041563
TI  - Needle stick suit: judgment for RN & employer upheld. Case on point: Scott V.
      Retz, 49A. 05-0904-CV-192 (11/10/2009)-IN.

PMID- 20041564
TI  - Predicting changes in older adults' interpersonal control strivings.
AB  - People vary in the importance they ascribe to, and efforts they invest in,
      maintaining positive relationships with others. Research has linked such
      variation in interpersonal control strivings to the quality of social exchanges
      experienced, but little work has examined the predictors of interpersonal control
      strivings. Given the importance of close relationships in later life, this study
      examined conditions that might precipitate increases or declines in interpersonal
      control strivings over a 2-year period. Specifically, change in interpersonal
      control strivings was hypothesized to be particularly influenced by the interplay
      of two co-occurring conditions: (1) experiences in the social environment that
      bolster or undermine older adults' motivation to foster satisfying social ties
      and (2) the availability of personal resources to respond to these experiences.
      The findings suggest that a change in older adults' interpersonal control
      strivings over a 2-year period was affected jointly by the frequency with which
      they experienced positive social exchanges and their health status. Features of
      the social environment, therefore, may interact with personal resources to
      influence interpersonal control strivings in later life.

PMID- 20041565
TI  - Predictors of physical functioning trajectories among Chinese oldest old adults:
      rural and urban differences.
AB  - This article examined the differences between rural/urban older adults in their
      trajectories of activities of daily living (ADL) over a 4-year period. The sample
      included 2,490 community dwelling older adults who completed three waves (1998,
      2000, and 2002) of the Chinese Longitudinal Healthy Longevity Survey. Among them,
      63.5% were from rural areas. Hierarchical linear modeling (HLM) was run for the
      whole sample and separately for rural and urban samples. For both rural and urban
      samples, older age and involvement in fewer activities predicted increases in ADL
      difficulties over time. In addition, being female and routinely smoking predicted
      increases in ADL difficulties for the rural sample. Implications for
      interventions to slow down ADL decline were discussed.

PMID- 20041566
TI  - The moderating role of age-group identification and perceived threat on
      stereotype threat among older adults.
AB  - Although research has shown that older adults are negatively affected by aging
      stereotypes, relatively few studies have attempted to identify those older adults
      who may be especially susceptible to these effects. The current research takes
      steps toward identifying older adults most susceptible to the effects of
      stereotype threat and investigates the consequence of stereotype threat on the
      well-being of older adults. Older adults were tested on their recall of a prose
      passage under normal or stereotype threatening conditions. Memory decrements for
      those in the threat condition were moderated by perceived stereotype threat such
      that greater decrements were seen for those who reported greater perceived
      threat. A similar pattern was observed for negative emotion, such that those in
      the threat condition who reported higher perceptions of threat experienced a
      greater decrease in positive emotions. Age group identification also proved to be
      an important factor, with the strongly identified performing worse than the
      weakly identified. As well, high age-group identification buffered some of the
      negative affective consequences associated with stereotype threat, which is
      consistent with some models of coping with stigma.

PMID- 20041568
TI  - The 2009 Gold Medal for Distinguished Service--Dr. Stephen F. Schwartz.

PMID- 20041567
TI  - Caregivers--who copes how?
AB  - Within gerontological caregiving research, there is a major emphasis on stresses
      and burdens of this role. Yet there has been little attention directed toward the
      coping strategies that caregivers engage in to cope with this role and the
      factors that influence their adoption of different coping strategies. This
      article examines coping strategies and change in coping strategy over a 1-year
      period. In particular the differential importance of caregiver capacity (such as
      social support, health, and personality) compared with careload (such as hours of
      caregiving and need of the care recipient) is examined within a path model. Data
      came from a purposive sample of caregivers experiencing heavy demands. Overall,
      problem-focused coping is used more often than emotion-focused coping (either
      positive or negative) or seeking social support, but caregivers use all types
      simultaneously. Caregiver capacity, specifically neuroticism, is the strongest
      predictor of problem-focused coping with those high in neuroticism less likely to
      use this strategy. High neuroticism also predicts less use overall and negative
      emotion-focused coping strategies. Few significant predictors emerge of change;
      those that did were caregiver capacity, not careload variables. The use of all
      coping strategies, except seeking social support which remained stable, decreased
      over a 1-year period.

PMID- 20041569
TI  - A milestone: more than $100 billion for dental services in 1 year--but will it
      last?
AB  - The question of how well prepared were the economics of dentistry for the
      consequences of the current recession are reviewed at the national and state
      levels. Marked variations in the use of dental services, expenditures for care,
      and the sources of funding are considered. The factors are considered as once
      again, the President and the Congress are laboring over proposals for national
      health insurance. What are the potential consequences for the practice of
      dentistry and the patients that are served? Which way should the profession lobby
      -for inclusion or exclusion?

PMID- 20041570
TI  - Epidemiologic survey of erosive tooth wear in San Antonio, Texas.
AB  - OBJECTIVES: To estimate the prevalence of erosive tooth wear in children aged 12
      17 years in the southwest region of San Antonio, Texas, within Bexar County.
      METHODS: A convenience sample of 307 children aged 12-17 years was selected from
      two junior high schools. The population consisted predominantly of Hispanic
      Mexican Americans. The true prevalence of erosive tooth wear within the US is
      known from only one study, and then only for limited sectors of the population.
      The Tooth Wear Index, Screening for Oral Health using the Association of State
      and Territorial Dental Directors (ASTDD) criteria and oral health and dietary
      assessment questionnaires were used as survey parameters. The questionnaire
      included data on detailed dietary habits relating primarily to the consumption of
      acidic beverages and foods. RESULTS: The overall prevalence of erosion within our
      convenience sample was 5.5 percent. All affected children showed erosive tooth
      wear low in severity and confined to the enamel with no exposed dentin. A chi
      square test was performed to test for associations between the presence of
      erosion and consumption level of certain acidic foods at a significance level of
      5 percent. Few significant and consistent associations were found between erosive
      tooth wear and consumption frequency categories of groups of acidic foods and
      beverages using a non-validated food intake questionnaire on purported risk
      foods. Soda drinks were associated. Mexican acidic foods were not. CONCLUSION:
      This study indicated a low prevalence and low severity of dental erosion in a
      convenience sample of children aged 12-17 years in southwest San Antonio, Texas.
      Issues of sampling and response bias preclude these findings being generalized to
      other populations and regions.The results should be viewed with caution. Because
      the local consumption of some purported risk foods appears to be increasing, this
      study provides a base-line for future assessments of erosive tooth wear in this
      population.

PMID- 20041571
TI  - High technology.
AB  - Technology has invaded our dental practices in many areas. Computer software and
      networks manage offices, while equipment now has sophisticated electronics to
      help us treat our patients more effectively. The Internet and cell phones have
      changed the way we communicate with each other, manufacturers, our patients, and
      even how we obtain some continuing education.

PMID- 20041572
TI  - Oral and maxillofacial pathology case of the month. Normal pulp with den
      invaginatus (dens in dente) and periapical cyst.

PMID- 20041573
TI  - Financial advantages. Preventative measures ensure the health of your accounts
      receivable.
AB  - Running a dental practice is no small task; from staying on the leading edge of
      new medical developments and products, to monitoring ever-changing dental
      insurance plans, to simply overseeing the fundamental day-to-day operations. But
      there is one area of your practice that can be streamlined to significantly
      improve your cash flow, minimize delinquencies and optimize fiscal operations.
      Your accounts receivable and collections can be economically and efficiently
      managed by a savvy combination of internal efforts and the partnership of a third
      party resource.

PMID- 20041574
TI  - Unintended consequences of health insurance through employment.

PMID- 20041575
TI  - Teenage driving, rural bugs in urban spaces, web scorecards to set public health
      priorities, and how primary care physicians should be taught.

PMID- 20041576
TI  - Graduated driver licensing policy in the Great Lakes states: current benefits and
      future potential.
AB  - BACKGROUND: Motor vehicle crashes are the leading cause of teenage deaths in the
      United States. Graduated Driver Licensing (GDL) policies effectively decrease
      teenage crash deaths. Emerging research is identifying the most effective
      components of GDL. This study examines GDL policies across 6 Great Lakes states,
      describing the beneficial impact, and investigating how evidence-based policy
      modifications could further reduce teenage driving deaths and injuries. METHODS:
      GDL policies were reviewed in 6 Great Lakes states (Illinois, Indiana, Michigan,
      Minnesota, Ohio, and Wisconsin). Incidence rate ratios for fatal and injury
      crashes for 16-year-old drivers were obtained from the Nationwide Review of GDL
      Study. Ratios were applied to the fatal and injury crashes reported from each
      state between 2002 and 2006 for 16-year-old drivers. The potential impact
      (crashes avoided) for each state was determined based on the state using a 3
      phase GDL policy (a learner and intermediate stage prior to full licensure). In
      addition, the impact on crash reductions for each state if they had employed 5 of
      the recommended GDL components was determined. RESULTS: All 6 states had a 3
      phase GDL policy, resulting in potential avoidance of 124 fatal and more than
      21,000 injury crashes. The 6 states had 1 to 3 of the qualifying GDL components.
      If these states had adopted 5 of the qualifying components, an additional 309
      fatal and more than 27,000 injury crashes could have been avoided. CONCLUSION:
      Three-phase GDL policy is effective at saving the lives of teenage drivers and
      vehicle occupants; evidence-based modification of GDL has the potential to
      further reduce teenage motor vehicle crash deaths and injuries.

PMID- 20041577
TI  - Does the surgical clerkship meet the needs of practicing primary care physicians?
AB  - INTRODUCTION: A substantial amount of medical students enter primary care (PC)
      specialty careers. With the interest in reforming the curriculum to align the
      needs of our students to practice in their chosen specialties, an evaluation of
      our current surgical clerkship was done with the needs of PC practitioners in
      mind. We explored the needs of selected PC physicians in Wisconsin in
      relationship to the surgical clerkship curriculum. METHODS: A survey was mailed
      to 186 PC physicians practicing in Wisconsin. Included in this group were
      internal medicine, family medicine, and pediatric physicians. One follow-up
      mailing and an e-mail were sent to all non-respondents. Respondents rated the
      importance of 10 curricular areas, including the specialties of general,
      orthopaedic, plastic, transplant, vascular, cardiothoracic, and pediatric
      surgery, as well as otolaryngology, neurosurgery, and urology. Respondents also
      rated the importance of exposure to 24 surgical diagnoses and identified office
      procedures important to PC physicians. RESULTS: A total of 84 PC physicians
      responded to the survey. The highest-ranked curricular areas were general
      surgery, orthopaedic surgery, and otolaryngology. The 5 diagnoses that received
      the highest ranking from the PC physicians surveyed were abdominal pain,
      gastrointestinal bleeding, gastroesophageal reflux disease (GERD), biliary
      tract/gallbladder disorders, and breast disease, all of which are included in the
      general surgery curriculum. The 5 most common office procedures important to PC
      physicians were suturing, local anesthetic administration, dressing/wound
      management, wound debridement, and insertion of intravenous cannula. CONCLUSIONS:
      Our survey confirmed the importance of core knowledge of general surgery and
      common general surgical disease processes to PC physicians. The need for
      additional exposure to otolaryngology and orthopaedic surgery was identified, as
      was as the importance of basic procedures. This information may be valuable to
      students interested in PC and inform the surgical clerkship curriculum in order
      to optimally prepare students for their chosen careers.

PMID- 20041578
TI  - The value of a web-based interactive regional health scorecard in setting public
      health priorities.
AB  - INTRODUCTION: Community-based health improvement efforts sometimes focus on
      emerging health issues rather than following a more proactive planning process.
      Although there is an abundance of easily accessible data on state and national
      websites, community leaders frequently don't know where to find data that will
      help them to prioritize local efforts. METHODS: The La Crosse Medical Health
      Science Consortium (LMHSC) is a formal collaborative of the 2 major health care
      providers and 3 higher education institutions in La Crosse, Wisconsin, and covers
      20 counties in western Wisconsin, southeastern Minnesota, and northeastern Iowa.
      To help prioritize regional health improvement efforts, we developed an
      interactive scorecard for each county, which allows for tracking indicators (ie,
      leading causes of death, accidents, cancer, health and behaviors, heart disease,
      infectious diseases, maternal and child health, sexually transmitted infections,
      and substance use/abuse) and monitoring health improvement efforts. The website
      www.communityscorecard.com allows the user to examine a county's statistics over
      time (as far back as 1998) and compare data among LMHSC's 20 counties, the state,
      and the nation as a whole. To aid prioritization, a grading schema allows each
      county to grade itself compared with selected health indicator benchmarks, like
      the Healthy People 2010 goals. RESULTS: Since going public in March 2007, the
      website has received more than 10,500 visits by more than 2300 unique users from
      48 states and 46 countries. CONCLUSIONS: Prioritization and engagement of the
      community in health promotion activities requires quick access to accurate data
      that have been translated into information. We describe the development of a web
      based population health scorecard for this purpose.

PMID- 20041579
TI  - Blastomycosis in urban southeastern Wisconsin.
AB  - PURPOSE: A previous study revealed a non-random distribution of blastomycosis
      cases by home site in urban Milwaukee County. This study was conducted to
      determine the proportion of cases with likely exposures solely in urban areas.
      METHODS: Records of 68 urban southeastern Wisconsin individuals, including 45
      residents of Milwaukee, 19 from suburban Milwaukee County, and 4 from outside
      Milwaukee County, diagnosed with blastomycosis between January 2002 and July 2007
      were studied using medical record reviews, case reports, and telephone
      interviews. Geographic Information Systems (GIS) proximity analysis was then used
      to compare the distance between case and control home sites to environmental risk
      factors. RESULTS: Of patients reporting their exposure history, 41 of 49 (84%)
      participated in outdoor work or leisure activities, and 12 of 47 (26%) engaged in
      fishing, hunting, camping, or hiking. Of the urban cases, 64 occurred among
      Milwaukee County residents; of those, 25 of 49 (51%) denied traveling, which
      suggests local urban exposure, and 8 of 11 (73%) specifically recalled urban
      waterway exposure prior to diagnosis. The 45 Milwaukee cases were concentrated on
      the north side of town and were closer to inland waterways than a random sample
      of 6528 controls (median 690 versus 1170 meters; P=0.003), but not closer to
      parks. CONCLUSION: Southeastern Wisconsin residents may acquire blastomycosis
      solely in their local urban area, sometimes without specific outdoor exposures.
      Proximity to inland waterways is associated with blastomycosis cases in urban
      areas, similar to rural areas of Wisconsin. Clinicians should include
      blastomycosis in appropriate differential diagnoses of symptomatic individuals,
      even in urban residents without travel history or history of significant outdoor
      exposures.

PMID- 20041580
TI  - Ethical considerations in mental health care informed by research.

PMID- 20041581
TI  - Kara Neumann, spiritual healing, and the law.

PMID- 20041582
TI  - MetaStar works with Wisconsin hospitals to decrease MRSA infections.

PMID- 20041583
TI  - Development and trends in the status of public guardianship: highlights of the
      2007 National Public Guardianship Study.

PMID- 20041584
TI  - Getting right with guidelines.

PMID- 20041585
TI  - Is it time to step up to stepped care with our cognitive-behavioral insomnia
      therapies?

PMID- 20041586
TI  - Sleepwalking deja vu.

PMID- 20041587
TI  - Can homemade video recording become more than a screening tool?

PMID- 20041588
TI  - Insomnia and hypertension.

PMID- 20041589
TI  - Narcolepsy and streptococcal infections.

PMID- 20041590
TI  - "Stepped care": a health technology solution for delivering cognitive behavioral
      therapy as a first line insomnia treatment.
AB  - There is a large body of evidence that Cognitive Behavioral Therapy for insomnia
      (CBT) is an effective treatment for persistent insomnia. However, despite two
      decades of research it is still not readily available, and there are no immediate
      signs that this situation is about to change. This paper proposes that a service
      delivery model, based on "stepped care" principles, would enable this relatively
      scarce healthcare expertise to be applied in a cost-effective way to achieve
      optimal development of CBT services and best clinical care. The research evidence
      on methods of delivering CBT, and the associated clinical leadership roles, is
      reviewed. On this basis, self-administered CBT is posited as the "entry level"
      treatment for stepped care, with manualized, small group, CBT delivered by
      nurses, at the next level. Overall, a hierarchy comprising five levels of CBT
      stepped care is suggested. Allocation to a particular level should reflect
      assessed need, which in turn represents increased resource requirement in terms
      of time, cost and expertise. Stepped care models must also be capable of
      "referring" people upstream where there is an incomplete therapeutic response to
      a lower level intervention. Ultimately, the challenge is for CBT to be delivered
      competently and effectively in diversified formats on a whole population basis.
      That is, it needs to become "scalable". This will require a robust approach to
      clinical governance.

PMID- 20041591
TI  - Sleep contribution to motor memory consolidation: a motor imagery study.
AB  - STUDY OBJECTIVES: Sleep is known to enhance performance following physical
      practice (PP) of a new sequence of movements. Apart from a pilot study, it is
      still unknown whether a similar sleep-dependent consolidation effect can be
      observed following motor imagery (MI) and whether this mnemonic process is
      related to MI speed. DESIGN: Counterbalanced within-subject design. SETTING: The
      laboratory. PARTICIPANTS: Thirty-two participants. INTERVENTIONS: PP, real-time
      MI, fast MI, and NoSleep (control) groups. MEASUREMENTS AND RESULTS: Subjects
      practiced an explicitly known sequence of finger movements, and were assigned to
      PP, real-time MI, or fast MI, in which they intentionally imagined the sequence
      at a faster pace. A NoSleep group subjected to real-time MI, but without any
      intervening sleep, was also tested. Performance was evaluated before practice, as
      well as prior to, and after a night of sleep or a similar time interval during
      the daytime. Compared with the NoSleep group, the results revealed offline gains
      in performance after sleep in the PP, real-time MI, and fast MI groups. There was
      no correlation between a measure of underestimation of the time to imagine the
      motor sequence and the actual speed gains after sleep, neither between the
      ease/difficulty to form mental images and performance gains. CONCLUSIONS: These
      results provide evidence that sleep contributes to the consolidation of motor
      sequence learning acquired through MI and further suggests that offline delayed
      gains are not related to the MI content per se. They extend our previous findings
      and strongly confirm that performance enhancement following MI is sleep
      dependent.

PMID- 20041592
TI  - Sleep behaviors and sleep quality in children with autism spectrum disorders.
AB  - STUDY OBJECTIVES: (1) Compare sleep behaviors of children with autism spectrum
      disorders (ASD) with sleep behaviors of typically developing (TD) children using
      the Children's Sleep Habits Questionnaire (CSHQ); (2) compare sleep quality-
      defined as mean activity, sleep latency, number of awakenings, sleep efficiency
      and total sleep time--of the cohort of children with ASD and TD, as measured by
      10 nights of actigraphy; and (3) estimate the prevalence of sleep disturbances in
      the ASD and TD cohorts. DESIGN: Descriptive cross-sectional study. SETTING: The
      Children's Hospital of Philadelphia. PARTICIPANTS: Randomly selected children
      from the Regional Autism Center. The ASD cohort of 59 children, aged 4 to 10
      years, (26 with autism, 21 with pervasive developmental disorder-not otherwise
      specified [PDD-NOS], and 12 with Asperger disorder) were compared with 40 TD
      control subjects. MEASUREMENTS AND RESULTS: The CSHQ, sleep diaries, and 10
      nights of actigraphy using the Sadeh algorithm of children with ASD and TD
      control subjects were compared. CSHQ showed 66.1% of parents of children with ASD
      (62.5% autism, 76.2% PDD-NOS, 58.3% Asperger disorder) and 45% of parents of the
      control subjects reported that their children had sleep problems. Actigraphic
      data showed that 66.7% of children with ASD (75% autism, 52.4% PDD-NOS, 75%
      Asperger disorder) and 45.9% of the control subjects had disturbed sleep.
      CONCLUSIONS: The prevalence estimate of 45% for mild sleep disturbances in the TD
      cohort highlights pediatric sleep debt as a public health problem of concern. The
      prevalence estimate of 66% for moderate sleep disturbances in the ASD cohort
      underscores the significant sleep problems that the families of these children
      face. The predominant sleep disorders in the ASD cohort were behavioral insomnia
      sleep-onset type and insomnia due to PDD.

PMID- 20041593
TI  - Abdominal compression increases upper airway collapsibility during sleep in obese
      male obstructive sleep apnea patients.
AB  - STUDY OBJECTIVES: Abdominal obesity, particularly common in centrally obese
      males, may have a negative impact on upper airway (UA) function during sleep. For
      example, cranial displacement of the diaphragm with raised intra-abdominal
      pressure may reduce axial tension exerted on the UA by intrathoracic structures
      and increase UA collapsibility during sleep. DESIGN: This study aimed to examine
      the effect of abdominal compression on UA function during sleep in obese male
      obstructive sleep apnea patients. SETTING: Participants slept in a sound
      insulated room with physiologic measurements controlled from an adjacent room.
      PARTICIPANTS: Fifteen obese (body mass index: 34.5 +/- 1.1 kg/m2) male
      obstructive sleep apnea patients (apnea-hypopnea index: 58.1 +/- 6.8 events/h)
      aged 50 +/- 2.6 years participated. INTERVENTIONS: Gastric (PGA) and
      transdiaphragmatic pressures (P(DI)), UA closing pressure (UACP), UA airflow
      resistance (R(UA)), and changes in end-expiratory lung volume (EELV) were
      determined during stable stage 2 sleep with and without abdominal compression,
      achieved via inflation of a pneumatic cuff placed around the abdomen. UACP was
      assessed during brief mask occlusions. MEASUREMENTS AND RESULTS: Abdominal
      compression significantly decreased EELV by 0.53 +/- 0.24 L (P=0.045) and
      increased PGA (16.2 +/- 0.8 versus 10.8 +/- 0.7 cm H2O, P < 0.001), P(DI) (11.7
      +/- 0.9 versus 7.6 +/- 1.2 cm H2O, P < 0.001) and UACP (1.4 +/- 0.8 versus 0.9 +/
      0.9 cm H2O, P = 0.039) but not R(UA)(6.5 +/- 1.4 versus 6.9 +/- 1.4 cm H2O x
      L/s, P=0.585). CONCLUSIONS: Abdominal compression negatively impacts on UA
      collapsibility during sleep and this effect may help explain strong associations
      between central obesity and obstructive sleep apnea.

PMID- 20041594
TI  - Obstructive sleep apnea and aldosterone.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a major risk factor for hypertension
      and has been associated with increased risk for cardiovascular morbidity. A
      dysregulated renin-angiotensin-aldosterone system may contribute to excess sodium
      retention and hypertension and may be activated in OSA. We tested the hypothesis
      that serum levels of aldosterone and plasma renin activity (PRA) are increased by
      apneic sleep in subjects without cardiovascular disease, compared to healthy
      control subjects. METHODS AND RESULTS: Plasma aldosterone level was measured in
      21 subjects with moderate to severe OSA and was compared to 19 closely matched
      healthy subjects. Plasma renin activity (PRA) was measured in 19 OSA patients and
      in 20 healthy controls. Aldosterone and PRA were measured before sleep (9 pm),
      after 5 hrs of untreated OSA ( 2am) and in the morning after awakening (6 am).
      There were no baseline (9pm) differences in serum aldosterone levels and PRA
      between the healthy controls and OSA patients (aldosterone: 55.2 +/- 9 vs 56.0 +/
      9 pg/mL; PRA: 0.99 +/- 0.15 vs. 1.15 +/- 0.15 ng/mL/hr). Neither several hours
      of untreated severe OSA nor CPAP treatment affected aldosterone levels and PRA in
      OSA patients. Diurnal variation of both aldosterone and PRA was observed in both
      groups, in that morning renin and aldosterone levels were higher than those
      measured at night before sleep. CONCLUSIONS: Our study shows that patients with
      moderate to severe OSA without co-existing cardiovascular disease have plasma
      aldosterone and renin levels similar to healthy subjects. Neither untreated OSA
      nor CPAP treatment acutely affect plasma aldosterone or renin levels.

PMID- 20041595
TI  - Eszopiclone prevents excitotoxicity and neurodegeneration in the hippocampus
      induced by experimental apnea.
AB  - STUDY OBJECTIVE: This study was designed to determine the effects of eszopiclone
      on apnea-induced excitotoxic synaptic processes and apoptosis in the hippocampus.
      DESIGN: Recurrent periods of apnea, which consisted of a sequence of apnea (75%
      SpO2), followed by ventilation with recovery to normoxia (> 95% SpO2), were
      induced for a period of three hours in anesthetized guinea pigs. The CA3 Schaffer
      collateral pathway in the hippocampus was stimulated and the field excitatory
      postsynaptic potential (fEPSP) response was recorded in CA1. Animals in the
      experimental group received an intravenous injection of eszopiclone (3 mg/kg) 10
      min prior to the initiation of the periods of recurrent apnea, and once every 60
      min thereafter; control animals received comparable injections of vehicle. At the
      end of the 3-h period of recurrent apnea, the animals were perfused, and
      hippocampal sections were immunostained in order to determine the presence of
      apoptosis, i.e., programmed cell death. ANALYSES AND RESULTS: Apnea resulted in a
      persistent increase in synaptic responsiveness of CA1 neurons as determined by
      analyses of the fEPSP. Eszopiclone antagonized the apnea-induced increase in the
      fEPSP. Morphological analyses revealed significant apoptosis of CA1 neurons in
      control animals; however, there was no significant apoptosis in eszopiclone
      treated animals. CONCLUSIONS: Eszopiclone was determined to suppress the apnea
      induced hyperexcitability of hippocampal CA1 neurons, thereby
      reducing/eliminating neurotoxicity. These data lend credence to our hypothesis
      that eszopiclone, exclusive of its hypnotic actions, has the capacity to function
      as a potent neuroprotective agent.

PMID- 20041596
TI  - Sleep and the transition to adolescence: a longitudinal study.
AB  - STUDY OBJECTIVES: To assess the links between sleep and pubertal development
      using a longitudinal design. DESIGN: Three consecutive annual assessments of
      sleep and pubertal development. Sleep was assessed using a week of home
      actigraphy. SETTING: Naturalistic sleep in the home setting of school children,
      Tel Aviv Area, Israel. PARTICIPANTS: A sample of 94 (41 boys) typically
      developing healthy school-age children (age range at first assessment: 9.9-11.2
      years). INTERVENTION: N/A. MEASUREMENTS AND RESULTS: The Petersen's Pubertal
      Development Scale (PDS) and Sexual Maturation Scale (SMS) were used to assess
      pubertal development, and a week of actigraphy served to assess naturalistic
      sleep patterns. The results reflect expected developmental trends: an increase in
      signs of pubertal maturation, delayed sleep onset, and shorter sleep time. After
      controlling for age, significant relationships were found between sleep onset
      time, true sleep time, and number of night wakings at Time 1 and pubertal ratings
      at Time 2, and pubertal changes from Time 1 to Time 2. Delayed and disrupted
      sleep at Time 1 predicted faster pubertal changes from Time 1 to Time 2. These
      results were supported by structural equation modeling. These findings were
      similar in boys and girls. CONCLUSIONS: Based on these longitudinal data, it
      appears that pubertal changes in sleep (delayed sleep phase and disrupted sleep
      patterns) antedate bodily changes associated with puberty. The underlying
      mechanisms explaining these predictive links should be further explored.

PMID- 20041597
TI  - Neonatal maternal separation disrupts regulation of sleep and breathing in adult
      male rats.
AB  - STUDY OBJECTIVES: Neonatal maternal separation (NMS) disrupts development of
      cardiorespiratory regulation. Adult male rats previously subjected to NMS are
      hypertensive and show a hypoxic ventilatory response greater than that of
      controls. These results have been obtained in awake or anesthetised animals, and
      the consequences of NMS on respiratory control during normal sleep are unknown.
      This study tested the following. HYPOTHESES: NMS augments respiratory variability
      across sleep-wake states, and NMS-related enhancement of the hypoxic ventilatory
      response occurs during sleep. METHODS: Two groups of adult rats were used:
      controls (no treatment) and rats subjected to NMS. Ventilatory activity,
      coefficient of variation, and hypoxic ventilatory response were compared between
      groups and across sleep-wake states. SUBJECTS: Male Sprague Dawley rats-NMS:
      n=11; controls: n=10. Pups subjected to NMS were isolated from their mother for 3
      hours per day from postnatal days 3 to 12. Controls were undisturbed.
      MEASUREMENTS AND RESULTS: At adulthood, sleep-wake states were monitored by
      telemetry, and ventilatory activity was measured using whole-body
      plethysmography. Sleep and breathing were measured for 2.5 hours (in the morning)
      while the rats were breathing room air. Data were analysed in 20-second epochs.
      Rats were then exposed to a brief (90-sec) hypoxic episode (nadir = 12% O2) to
      measure the hypoxic ventilatory response. The coefficient of variability for
      tidal volume and breathing frequency decreased during sleep but remained more
      elevated in NMS rats than in controls. During non-rapid eye movement sleep, the
      breathing-frequency response to hypoxia of NMS rats was significantly greater
      than that of controls. CONCLUSION: Neonatal maternal separation results in
      persistent disruption of respiratory control during sleep.

PMID- 20041599
TI  - Dream-enacting behaviors in a normal population.
AB  - STUDY OBJECTIVES: Determine the prevalence and gender distributions of behaviors
      enacted during dreaming ("dream-enacting [DE] behaviors") in a normal population;
      the independence of such behaviors from other parasomnias; and the influence of
      different question wordings, socially desirable responding and personality on
      prevalence. DESIGN: 3-group questionnaire study. SETTING: University classrooms
      PARTICIPANTS: Three undergraduate samples (Ns = 443, 201, 496; mean ages = 19.9
      +/- 3.2 y; 20.1 +/- 3.4 y; 19.1 +/- 1.6 y). INTERVENTIONS: N/A. MEASUREMENTS AND
      RESULTS: Subjects completed questionnaires about DE behaviors and Social
      Desirability. Study 1 employed a nonspecific question about the behaviors, Study
      2 employed the same question with examples, and Study 3 employed 7 questions
      describing specific behavior subtypes (speaking, crying, smiling/laughing, fear,
      anger, movement, sexual arousal). Somnambulism, somniloquy, nightmares, dream
      recall, alexithymia, and absorption were also assessed. Factor analyses were
      conducted to determine relationships among DE behaviors and their independence
      from other parasomnias. Prevalence increased with increasing question specificity
      (35.9%, 76.7%, and 98.2% for the 3 samples). No gender difference obtained for
      the nonspecific question, but robust differences occurred for more specific
      questions. Females reported more speaking, crying, fear and smiling/laughing than
      did males; males reported more sexual arousal. When controlling other parasomnias
      and dream recall frequency, these differences persisted. Factor solutions
      revealed that DE behaviors were independent of other parasomnias and of dream
      recall frequency, except for an association between dream-talking and somniloquy.
      Sexual arousal was related only to age. Behaviors were independent of alexithymia
      but moderately related to absorption. CONCLUSIONS: Dream-enacting behaviors are
      prevalent in healthy subjects and sensitive to question wording but not social
      desirability. Subtypes are related, differ with gender and occur independently of
      other parasomnias.

PMID- 20041598
TI  - Dreamlike mentations during sleepwalking and sleep terrors in adults.
AB  - BACKGROUND: Sleep terrors and sleepwalking are described as arousals from slow
      wave sleep with no or poor mental recollection. OBJECTIVE: To characterize the
      mental content retrospectively associated with sleep terrors or sleepwalking.
      SETTING: University Hospital. DESIGN: Controlled prospective cohort.
      PARTICIPANTS: Forty-three patients referred for severe sleepwalking/sleep terrors
      (age: 26 +/- 7 y, 46% men, 5 with sleep terrors only, 8 with sleepwalking only,
      and 30 with both), matched with 25 healthy control subjects. INTERVENTION: Thirty
      eight of the 43 patients (88%) underwent an interview about the frequency, time,
      behaviors, and mental content associated with the episodes of sleepwalking and
      sleep terrors, whenever they occurred over a lifetime. The mental contents were
      classified for complexity (Orlinski score), and for characters, emotions,
      fortune/misfortune, and social interactions (Hall and Van de Castle categories).
      Patients and control subjects underwent an overnight video-polysomnogram.
      RESULTS: Seventy-one percent of the patients reported at least 1 dreamlike
      mentation associated with the sleepwalking/sleep terrors episode. The dreamlike
      mentation action corresponded with the observed behavior. A total of 106
      dreamlike mentations were collected (mean: 3 +/- 3.4 dreamlike
      mentations/patient, range 0-17). Most (95%) dreamlike mentations consisted of a
      single visual scene. These dreamlike mentations were frequently unpleasant, with
      aggression in 24% (the dreamer being always the victim), misfortune in 54%, and
      apprehension in 84%. The patients with dream mentations reported more severe
      daytime sleepiness. CONCLUSION: Short, unpleasant dreamlike mentations may occur
      during sleepwalking/sleep terrors episodes, suggesting that a complex mental
      activity takes place during slow wave sleep. Sleepwalking may thus represent
      acting out of the corresponding dreamlike mentation.

PMID- 20041600
TI  - NREM arousal parasomnias and their distinction from nocturnal frontal lobe
      epilepsy: a video EEG analysis.
AB  - STUDY OBJECTIVES: To describe the semiological features of NREM arousal
      parasomnias in detail and identify features that can be used to reliably
      distinguish parasomnias from nocturnal frontal lobe epilepsy (NFLE). DESIGN:
      Systematic semiologial evaluation of parasomnias and NFLE seizures recorded on
      video-EEG monitoring. PATIENTS: 120 events (57 parasomnias, 63 NFLE seizures)
      from 44 subjects (14 males). Interventions. The presence or absence of 68
      elemental clinical features was determined in parasomnias and NFLE seizures.
      Qualitative analysis of behavior patterns and ictal EEG was undertaken.
      Statistical analysis was undertaken using established techniques. RESULTS:
      Elemental clinical features strongly favoring parasomnias included: interactive
      behavior, failure to wake after event, and indistinct offset (all P < 0.001).
      Cluster analysis confirmed differences in both the frequency and combination of
      elemental features in parasomnias and NFLE. A diagnostic decision tree generated
      from these data correctly classified 94% of events. While sleep stage at onset
      was discriminatory (82% of seizures occurred during stage 1 or 2 sleep, with 100%
      of parasomnias occurring from stage 3 or 4 sleep), ictal EEG features were less
      useful. Video analysis of parasomnias identified three principal behavioral
      patterns: arousal behavior (92% of events); non-agitated motor behavior (72%);
      distressed emotional behavior (51%). CONCLUSIONS: Our results broadly support the
      concept of confusion arousals, somnambulism and night terrors as prototypical
      behavior patterns of NREM parasomnias, but as a hierarchical continuum rather
      than distinct entities. Our observations provide an evidence base to assist in
      the clinical diagnosis of NREM parasomnias, and their distinction from NFLE
      seizures, on semiological grounds.

PMID- 20041602
TI  - [The clinical value of dynamic posturography in the peripheral vertigo].
AB  - OBJECTIVE: To explore the clinical value of dynamic posturography in the
      diagnosis of peripheral vertigo. METHOD: One hundred and sixty peripheral vertigo
      patients with full clinical documents in vertigo clinic of our hospital from May
      2007 to May 2008 were retrospectively analyzed in this study. All the patients
      firstly underwent the inspection of static and dynamic posturography and then
      were subjected to caloric test using videonystagmography. The results were
      conducted a comparative analysis. Surface of the statokinesigram (SSKG) was
      selected as assessment parameter of static posturography. The result of sensory
      organization test (SOT) were selected as assessment parameters of dynamic
      posturography. The unilateral weakness was selected as assessment parameter of
      caloric test. Twenty normal subjects were selected as control. RESULT: Among the
      160 cases with peripheral vertigo, results of SOT in dynamic posturography were
      abnormal in 144 cases, with a sensitivity of 90.0%; caloric test was abnormal in
      110 cases, with a sensitivity of 68.8%; static posturography was abnormal in 76
      cases, with a sensitivity of 47.5%. There existed a statistically significant
      difference between dynamic posturography and caloric test or static
      posturography. There were 40 patients (25.0%) who had normal caloric test results
      in which dynamic posturography findings were abnormal. Among the 20 cases of
      normal people, results of SOT in dynamic posturography were abnormal in only one
      case (5.0%). CONCLUSION: With its superior sensitivity and specificity, dynamic
      posturography has been an objective and reliable approach in the diagnosis of
      peripheral vertigo. It can help to confirm the presence of abnormalities in some
      peripheral vertigo patients whose caloric results are normal.

PMID- 20041601
TI  - Polysomnographic abnormalities in succinic semialdehyde dehydrogenase (SSADH)
      deficiency.
AB  - OBJECTIVES: Patients with SSADH deficiency, a disorder of chronically elevated
      endogenous GABA and GHB, were studied for sleep symptoms and polysomnography. We
      hypothesized that patients would have excessive daytime somnolence and decreased
      REM sleep. DESIGN: Polysomnography and MSLT were performed on patients enrolled
      for comprehensive clinical studies of SSADH deficiency. SETTING: Sleep studies
      were obtained in the sleep laboratories at CNMC and NIH. PATIENTS: Sleep
      recordings were obtained in 10 patients with confirmed SSADH deficiency.
      INTERVENTIONS: Thirteen overnight polysomnograms were obtained in 10 patients (7
      male, 3 female, ages 11-27 y). Eleven MSLT studies were completed in 8 patients.
      MEASUREMENTS AND RESULTS: Polysomnograms showed prolongation of REM stage latency
      (mean 272 +/- 89 min) and decreased percent stage REM (mean 8.9%, range 0.3% to
      13.8%). Decreased mean sleep latency was present in 6 of 11 MSLTs. CONCLUSIONS:
      SSADH deficiency is associated with prolonged latency to stage REM and decreased
      percent stage REM. This disorder represents a model of chronic GABA and GHB
      accumulation associated with suppression of REM sleep.

PMID- 20041603
TI  - [Construction of GJB2 mutations common in Chinese EGFP fusion protein vectors].
AB  - OBJECTIVE: To construct GJB2 gene mutations common in Chinese EGFP fusion protein
      vectors, and to search for better way to study the mechanism of deletion
      mutations in GJB2 gene. METHOD: Non-fusion protein vectors of 235delC, 299-300
      del AT and 176 del 16 bp were first made by point mutation methods in vitro. Then
      expression part of the upper 3 mutations were amplified by PCR and the PCR
      products were cloned into TA cloning vector. After cutting by restriction enzymes
      EcoRI/BamHI, three deletion mutations were inserted into pEGFP-N1 vector.
      Sequencing was used to verify the validity of the fusion protein vectors. HEK293
      cells were transfected with the recombinant DNA samples by the liposome complex
      method. RESULT: The recombined plasmids were highly expressed in HEK293 cells.
      Green fluorescence signals were distributed uniformly in cytoplasm. CONCLUSION:
      GJB2 mutations common in Chinese EGFP fusion protein vectors were constructed
      successfully. It may provide a better way to explore the reasons of nonsyndromic
      hearing loss common in Chinese.

PMID- 20041604
TI  - [Vestibular testing abnormalities in individuals with motion sickness].
AB  - OBJECTIVE: To evaluate the vestibular function of motion sickness. METHOD: VNG,
      which tests the vestibular function of horizontal semicircular canal, and CPT,
      which tests vestibulospinal reflex and judge proprioceptive, visual and
      vestibular status, were performed in 30 motion sickness patients and 20 healthy
      volunteers (control group). Graybiel score was recorded at the same time. RESULT:
      Two groups' Graybiel score (12.67 +/- 11.78 vs 2.10 +/- 6.23; rank test P<0.05),
      caloric test labyrinth value [(19.02 +/- 8.59) degrees/s vs (13.58 +/- 5.25)
      degrees/s; t test P<0.05], caloric test labyrinth value of three patients in
      motion sickness group exceeded 75 degrees/s. In computerized posturography
      testing (CPT), motion sickness patients were central type (66.7%) and disperse
      type (23.3%); all of control group were central type. There was statistical
      significance in two groups' CTP area, and motion sickness group was obviously
      higher than control group. While stimulating vestibulum in CPT, there was
      abnormality (35%-50%) in motion sickness group and none in control group.
      Generally evaluating CPT, there was only 2 proprioceptive hypofunction, 3 visual
      hypofunction, and no vestibular hypofunction, but none hypofunction in control
      group. CONCLUSION: Motion sickness patients have high vestibular susceptible,
      some with vestibular hyperfunction. In posturography, a large number of motion
      sickness patients are central type but no vestibular hypofunction, but it is hard
      to keep balance when stimulating vestibulum.

PMID- 20041605
TI  - [A study on early hearing impairment with essential hypertension].
AB  - OBJECTIVE: To study the characteristic of hearing loss in essential hypertension.
      METHOD: Sixty-eight cases (136 ears) of patients with essential hypertension were
      divided into two groups, i.e. group A, patients without retinal arteriosclerosis
      (35 cases, 70 ears ) and group B, patients with retinal arteriosclerosis (33
      cases, 66 ears ). The control group consisted of 30 cases (60 ears) of the same
      sex and same age. All people were measured by pure tone audiometry and distortion
      product otoacoustic emissions. RESULT: The pure tone thresholds measured in group
      B hypertensive patients were significantly higher than in the normal controls
      (P<0.05), whereas pure tone thresholds in group A were not different from those
      in the control group (P>0.05). From 1000 to 8000 Hz, DPOAE amplitudes of
      hypertensive group A and group B were lower than that in control group (P<0.01).
      Only on the frequency points of 4000 Hz, the detection rate of DPOAE in group B
      was lower than that in control group (P<0.05). CONCLUSION: Hypertension is a risk
      factor of degeneration of the hearing apparatus. The hearing function of
      hypertensive patients has probability to be impaired, although they do not feel
      hearing loss.

PMID- 20041606
TI  - [Primary study of diagnosis and treatment of huge petrous apex cholesteatoma
      (clinical analysis of 2 cases)].
AB  - OBJECTIVE: To investigate the clinical features, operative approach and method of
      petrous apex cholesteatoma, to improve the effect of operation and to reduce
      surgical complications. METHOD: Two cases of patients with giant petrous apex
      cholesteatoma were treated by trans labyrinth approach, one of which was
      successfully operated with oto-endoscope-assisted surgery. RESULT: No
      cerebrospinal fluid leakage, infection, vertigo or disequilibrium was found in
      the two cases after operation. CONCLUSION: Temporal CT and MRI are of great
      importance in clinical diagnosis and choice of surgical approach. Surgery by
      trans-labyrinth approach paves way for removing cholesteatoma thoroughly, dealing
      with facial nerve and repairing cerebrospinal fluid leakage. Surgery is
      considered to be the only way to cure petrous apex cholesteatoma, while the key
      procedure to prevent recurrence lies in complete removal of lesion, long-time
      strict follow up and regular clearance of the surgical field.

PMID- 20041607
TI  - [Study on multi-area universal newborn hearing screening in countryside of
      China].
AB  - OBJECTIVE: To investigate the feasibility of universal newborn hearing screening
      in countryside in order to provide reliable evidence in launching this program
      all over the countryside of China. METHOD: Subjects were 12,638 infants who were
      born in 9 counties from Jan 2004 to Dec 2005. TEOAE was used for the fast hearing
      screening. Infants were screened on the 2-7 days after the birth. The re
      screening was conducted in 4-6 weeks if failed in the initial screening, and
      follow-up were provided continually if they also failed in the re-screening.
      RESULT: Ten thousand eight hundred and forty-five of 12,638 (85.8%) were screened
      including 9,963 (91.9%) normal newborns and 882 (8.1%) newborns with high-risk.
      Seven thousand four hundred and fifty (68.7%) newborns passed the initial
      screening, and 3,395 (31.3%) people failed. One thousand seven hundred and ninety
      three (14.2%) infants were refused to be screened. Only 2,536 (74.7%) were re
      screened on time, and 859 (25.3%) did not receive re-screening. One hundred and
      twenty were failed in the re-screening or first screening, and 79 (65.8%) of them
      received diagnostic assessment. Among the infants received diagnostic assessment,
      6 (7.6%) cases were found to have profound hearing loss in both ears, 9 (11.4%)
      cases were found to be severe hearing loss (7 in both ears and 2 in single ear),
      11 (13.9%) cases were found to be moderate hearing loss (5 in both ear and 6 in
      single ear), 26 (32.9%) were found to have slight hearing loss (11 in both ear
      and 15 in single ears), and 27 (34.2%) were normal. Fifty-two infants were
      diagnosed as hearing loss with a prevalence of congenital hearing loss (in
      binaural and monaural) of 0.5% (52/10845) and a prevalence of bilateral hearing
      loss of 0.3% (29/10845). A prevalence of congenital hearing loss was 0.2%
      (22/9,963) in well infants and 3.4% (30/882) in high risk infants. Among the 13
      cases of children with severe and profound hearing loss in both ears children, 8
      (61.5%) cases were fitted with hearing aids and 1 (7.7%) case was implanted with
      cochlear implants. CONCLUSION: It is necessary and feasible to conduct hearing
      screening program in the rural area. However, the suitable model to perform the
      program in the countryside needs to be set up as soon as possible in order to get
      more poor infants to participate into the hearing screening program for free and
      increase the screening rate.

PMID- 20041608
TI  - [The complications of traumatic optic neuropathy].
AB  - OBJECTIVE: To investigate the complications of traumatic optic neuropathy and to
      call the surgeons attention to precaution. METHOD: Retrospectively analysis of
      122 cases patients with traumatic optic neuropathy and 3 cases were analyzed in
      detail including 1 case with purulent meningitis, another 1 case with internal
      carotid artery pseudoaneurysm and the other 1 case with internal carotid artery
      cavernous sinus fistula. RESULT: Most of the patients had the complications of
      orbital fracture, maxillofacial fracture, ocular and craniocerebral injury. A few
      of patients had other injuries all over the body. The case with purulent
      meningitis was cured with antibiotics. The case with internal carotid artery
      pseudoaneurysm was cured with neurosurgery. The visual acuity of the both cases
      were improved. The case with internal carotid artery cavernous sinus fistula died
      of severe hemorrhage. CONCLUSION: The patient with traumatic optic neuropathy has
      the possibility of severe cranial disorders, orbital fracture, maxillofacial
      fracture and injuries of viscera or limbs. It should be paid more attention and
      treated accordingly.

PMID- 20041609
TI  - [The characteristics of auditory brainstem response in preterm very low birth
      weight babies].
AB  - OBJECTIVE: To discuss the characteristics of auditory brainstem response in
      preterm very low birth weight (VLBW) babies and to investigate the correlations
      between the ABR and clinical characteristics. METHOD: Fifty-nine VLBW babies (118
      ears) were enrolled in the study and 30 term normal babies as the control group.
      Tympanometry, acoustic reflex, DPOAE, ABR were obtained in all the babies.
      RESULT: The prevalence of hearing loss in VLBW babies was higher than normal term
      babies and babies with perinatal complications higher than those without
      perinatal complications. There was no correlations between ABR threshold and
      gestational age, birth weight, postconceptional age, negative correlations
      between wave I, III and V latencies I - III, III - V and I - V intervals and
      postconceptional age. Wave I and V latencies, I - III and III - V intervals
      differed significantly between the two groups. CONCLUSION: The perinatal
      complications were the most important causes of the hearing loss in preterm VLBW
      babies than the gestational age and birth weight. There was a high prevalence of
      peripheral hearing loss in the preterm VLBW babies. Combining OAE and automated
      ABR should be applied for hearing screening. Regular follow-up was very important
      in all the preterm VLBW neonatal.

PMID- 20041611
TI  - Staff feeling the strain--before winter sets in.

PMID- 20041610
TI  - [Tiapride with the horn of saiga tatarica in the treatment of hemifacial spasm].
AB  - OBJECTIVE: Tiapride has been used effectively in the clinic for the treatment of
      dyskinesias and tic disorders including Tourette syndrome. The purpose of the
      retrospective study is to evaluate the effectiveness of tiapride with the horn of
      saiga tatarica in treatment of hemifacial spasm. METHOD: Twenty-eight patients
      with idiopathic hemifacial spasm, who were previously treated with carbamazepine,
      or acupuncture, or botulinum toxin injection, but refused to continue the
      previous therapies, were treated with tiapride, at a dosage of 50 mg/time once to
      thrice per day, combined with the horn of saiga tatarica at a dosage of 0.15 g to
      0.30 g/time once per day. The dosage of tiapride can been up to 100 mg/time once
      to thrice per day in some cases if necessary. The effectiveness of the therapy
      was evaluated from the time of three months after the beginning of the treatment.
      The main efficacy parameter was the degree of spasm reduction, that is, the
      classification of spasm before versus after the treatment. RESULT: The duration
      of following up is between 3 months and 12 months. Twenty-five cases out of 28
      patients have demonstrated a significant reduction of spasm. Of which, eight
      cases were completely relieved, 12 cases marked relieved and 5 cases partially
      relieved. The effective rate is 89.29%. CONCLUSION: Tiapride combined with the
      horn of saiga tatarica was effective and safe in reducing hemifacial spasm.
      However, further data from blinded trials and long-term following up are required
      before this treatment can be considered to be one of the main medical treatment
      options for hemifacial spasm.

PMID- 20041612
TI  - Metrics enable the profession to take control of nursing quality.

PMID- 20041613
TI  - Following the patient journey to improve medicines management and reduce errors.
AB  - Patient safety is a major concern in the NHS, and medicines management is a vital
      aspect of this. This article describes one patient's journey through healthcare
      from the perspective of how medicines are managed. The patient's journey starts
      with an emergency admission to hospital, followed by a 10 day inpatient stay,
      including a brief stay in the high dependency unit, through to discharge. Adverse
      events or near misses are highlighted, showing key areas where nurses need to
      take action to ensure or improve patient safety.

PMID- 20041614
TI  - Exploring the factors contributing to drug errors and how to improve knowledge.
AB  - Medicines administration is one of the high risk areas for nursing practice and a
      matter of considerable concern for practitioners, policymakers and the public.
      Drug errors can lead to devastating consequences for patients and for nurses'
      careers. It is an integral part of nurses' role, underpinned by legal and
      professional requirements (Nursing and Midwifery Council, 2008a). This article
      reviews the situation and makes suggestions on how to improve knowledge.

PMID- 20041615
TI  - Understanding the role of genetics and genomics in health 2: implications for
      practice.
AB  - This second article in a two part series on genetics and genomics in healthcare
      focuses on the implications for nursing practice. Part 1 examined the progress of
      research in this area and discussed the implications for healthcare. This part
      outlines the nurse's role in supporting the patient pathway, and some of the
      ethical issues and challenges facing nurses as they integrate genomic healthcare
      into practice.

PMID- 20041616
TI  - Adult obesity 2: treatment and management options for weight loss and
      maintenance.
AB  - This second in a two part unit discusses the various management options available
      to treat people who are overweight or obese. Part 1 examined the multifaceted
      causes of obesity, the rising prevalence, consequences and patient assessment.
      This part outlines management options, including dietary change, physical
      activity, pharmacotherapy and surgery. The issue of how to maintain weight once
      lost is also examined.

PMID- 20041617
TI  - There is more to care for the dying than hand-holding.

PMID- 20041618
TI  - An all graduate profession gives nursing new value.

PMID- 20041619
TI  - Creating a safer work environment.
AB  - The perioperative environment is associated with many hazards both for staff and
      patients. Practitioners throughout the world assess the risks and take action to
      mitigate these--an example of this is the many policies and procedures associated
      with infection prevention.

PMID- 20041620
TI  - Boogie woogie bugle boy.

PMID- 20041621
TI  - The Nursing and Midwifery Council make me rant again.

PMID- 20041622
TI  - An unusual hiding place.

PMID- 20041623
TI  - The NHS? ... it makes you sick.

PMID- 20041624
TI  - Who is in your operating theatre?
AB  - The presence of healthcare industry representatives poses a challenge for
      operating department managers. The healthcare industry is taken largely on trust,
      but in an era of clinical governance this is no longer acceptable. Managers need
      to establish criteria against which competencies can be measured to risk manage
      the presence of company personnel in theatre and maintain a safe environment for
      the patient.

PMID- 20041625
TI  - The growth of complementary therapies: and their benefits in the perioperative
      setting.
AB  - Complementary therapies support and enhance the quality of life and people's
      wellbeing. Increasingly, people are seeking out complementary therapies in
      managing their healthcare. Practitioners in the perioperative setting, who are at
      the forefront of healthcare delivery, should be aware of the current
      complementary therapies available to patients, including the potential benefits
      and any contraindications of the therapies.

PMID- 20041626
TI  - Anaesthetic medicines: back to basics.
AB  - Anaesthesia has developed since the first description of curare. Today there are
      a myriad of anaesthetic and analgesic medicines available. This article explores
      the function of medicines in a patient's perioperative journey and describes how
      pharmacokinetics and pharmacodynamics play such a large role. The different
      routes of administration are described and the main categories of anaesthetic
      medicines outlined. The characteristics and precautions associated with the
      different classes of medicines are highlighted.

PMID- 20041627
TI  - Not just a patient that snores. Obstructive sleep apnoea: the perioperative
      concerns through the eye of the anaesthetist.
AB  - Obstructive sleep apnoea (OSA) has life threatening perioperative
      cardiorespiratory implications. As patients present to hospital for incidental
      surgery unaware of their condition, perioperative practitioners need a thorough
      knowledge of OSA to allow optimisation before theatre. Elective cases should be
      delayed for investigation and treatment if OSA is suspected. In theatre
      cardiorespiratory problems should be managed by a senior anaesthetist and a
      perioperative team alert to the risk of post-operative hypoxia.

PMID- 20041628
TI  - Louisa Garrett Anderson: suffragette and First World War military surgeon.

PMID- 20041629
TI  - Molecular transfer printing using block copolymers.
AB  - Soft lithographic techniques augment or enhance the capabilities of traditional
      patterning processes and expand the diversity of materials that can be patterned.
      Realization of robust parallel techniques for creating chemical patterns at the
      nanoscale has been challenging. Here we present a method for creating and
      replicating chemical patterns that uses functionalized homopolymer inks that are
      preferentially segregated into the nanodomains of phase-separated diblock
      copolymer films. The inks are transferred by reaction to substrates that are
      brought into contact with block copolymer films, creating chemical patterns on
      the substrate that mirror the domain structure present at the film surface with
      high fidelity and resolution. In addition to printing from self-assembled domain
      structures, we can also direct the assembly of the block copolymer films from
      which transfer occurs using lithographically defined masters so as to replicate
      and transfer patterns of inks with controlled and well-defined geometries. The
      transferred patterns may be at higher resolution than the lithographically
      defined master, and the process can be repeated to create multiple copies of
      identical replicas. Transfer of one ink from one block of the copolymer is also
      possible, and filling the interspatial regions of the pattern with a second ink
      provides a pathway toward creating patterns with diverse chemical
      functionalities.

PMID- 20041630
TI  - Improved thermoelectric behavior of nanotube-filled polymer composites with
      poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate).
AB  - The thermoelectric properties of carbon nanotube (CNT)-filled polymer composites
      can be enhanced by modifying junctions between CNTs using poly(3,4
      ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), yielding high
      electrical conductivities (up to approximately 40000 S/m) without significantly
      altering thermopower (or Seebeck coefficient). This is because PEDOT:PSS
      particles are decorated on the surface of CNTs, electrically connecting junctions
      between CNTs. On the other hand, thermal transport remains comparable to typical
      polymeric materials due to the dissimilar bonding and vibrational spectra between
      CNT and PEDOT:PSS. This behavior is very different from that of typical
      semiconductors whose thermoelectric properties are strongly correlated. The
      decoupled thermoelectric properties, which is ideal for developing better
      thermoelectric materials, are believed to be due to thermally disconnected and
      electrically connected contact junctions between CNTs. Carrier transport at the
      junction is found to be strongly dependent on the type and concentration of
      stabilizers. The crucial role of stabilizers was revealed by characterizing
      transport characteristics of composites synthesized by electrically conducting
      PEDOT:PSS and insulating gum Arabic (GA) with 1:1-1:4 weight ratios of CNT to
      stabilizers. The influence of composite synthesis temperature and CNT-type and
      concentration on thermoelectric properties has also been studied. Single-walled
      (SW) CNT-filled composites dried at room temperature followed by 80 degrees C
      exhibited the best thermoelectric performance in this study. The highest
      thermoelectric figure of merit (ZT) in this study is estimated to be
      approximately 0.02 at room temperature, which is at least one order of magnitude
      higher than most polymers and higher than that of bulk Si. Further studies with
      various polymers and nanoparticles with high thermoelectric performance may
      result in economical, lightweight, and efficient polymer thermoelectric
      materials.

PMID- 20041631
TI  - P25-graphene composite as a high performance photocatalyst.
AB  - Herein we obtained a chemically bonded TiO(2) (P25)-graphene nanocomposite
      photocatalyst with graphene oxide and P25, using a facile one-step hydrothermal
      method. During the hydrothermal reaction, both of the reduction of graphene oxide
      and loading of P25 were achieved. The as-prepared P25-graphene photocatalyst
      possessed great adsorptivity of dyes, extended light absorption range, and
      efficient charge separation properties simultaneously, which was rarely reported
      in other TiO(2)-carbon photocatalysts. Hence, in the photodegradation of
      methylene blue, a significant enhancement in the reaction rate was observed with
      P25-graphene, compared to the bare P25 and P25-CNTs with the same carbon content.
      Overall, this work could provide new insights into the fabrication of a TiO(2)
      carbon composite as high performance photocatalysts and facilitate their
      application in the environmental protection issues.

PMID- 20041632
TI  - Assembly of nanorods into designer superstructures: the role of templating,
      capillary forces, adhesion, and polymer hydration.
AB  - The assembly mechanism by which hundreds of thousands of two-segment gold
      polypyrrole nanorods are assembled into kinetically controlled shape-directed
      superstructures is examined to predict the range of nanoparticle sizes and
      materials that can be utilized in their formation. Four processes are responsible
      for assembly: templating, capillary force assembly, adhesion, and polymer
      hydration. It is shown that templating, where rods are prepositioned for
      assembly, is scale invariant and that the energy-minimized state after this step
      is highly disordered. In addition, we predict that superstructures can be made
      independently from patterns of rods separated by a distance as small as six times
      the inter-rod spacing. Both modeling and experiment show that adhesion and
      polymer dehydration, which induces curvature in the superstructures, are
      applicable to other materials. However, the high surface energy and low elastic
      modulus of polypyrrole are advantageous toward generating three-dimensional
      structures, inducing curvature at gold/polypyrrole length ratios as large as 7:1.

PMID- 20041633
TI  - Hollow/rattle-type mesoporous nanostructures by a structural difference-based
      selective etching strategy.
AB  - A novel "structural difference-based selective etching" strategy has been
      developed to fabricate hollow/rattle-type mesoporous nanostructures, which was
      achieved by making use of the structural differences, rather than traditional
      compositional differences, between the core and the shell of a silica
      core/mesoporous silica shell structure to create hollow interiors. Highly
      dispersed hollow mesoporous silica spheres with controllable particle/pore sizes
      could be synthesized by this method, which show high loading capacity (1222 mg/g)
      for anticancer drug (doxorubicin). Hemolyticity and cytotoxicity assays of hollow
      mesoporous silica spheres were conducted, and the synthesized hollow mesoporous
      silica spheres with large pores show ultrafast immobilization of protein-based
      biomolecules (hemoglobin). On the basis of this strategy, different kinds of
      heterogeneous rattle-type nanostructures with inorganic nanocrystals, such as Au,
      Fe(2)O(3), and Fe(3)O(4) nanoparticles, as the core and mesoporous silica as the
      shell were also prepared. This strategy could be extended as a general approach
      to synthesize various hollow/rattle-type nanostructures by creating adequate
      structural differences between cores and shells in core/shell structures in
      nanoscale.

PMID- 20041634
TI  - Ultrasensitive, multiplexed detection of cancer biomarkers directly in serum by
      using a quantum dot-based microfluidic protein chip.
AB  - Sensitive and selective detection for cancer biomarkers are critical in cancer
      clinical diagnostics. Here we developed a microfluidic protein chip for an
      ultrasensitive and multiplexed assay of cancer biomarkers. Aqueous-phase
      synthesized CdTe/CdS quantum dots (aqQDs) were employed as fluorescent signal
      amplifiers to improve the detection sensitivity. Secondary antibodies (goat anti
      mouse IgG) were conjugated to luminescent CdTe/CdS QDs to realize a versatile
      fluorescent probe that could be used for multiplexed detection in both sandwich
      and reverse phase immunoassays. We found that our microfluidic protein chip not
      only possessed ultrahigh femtomolar sensitivity for cancer biomarkers, but was
      selective enough to be directly used in serum. This protein chip thus combines
      the high-throughput capabilities of a microfluidic network with the high
      sensitivity and multicolor imaging ability offered by highly fluorescent QDs,
      which can become a promising diagnostic tool in clinical applications.

PMID- 20041636
TI  - Study of enzymatic digestion of cellulose by small angle neutron scattering.
AB  - Small angle neutron scattering (SANS) was used to study the structure of Avicel
      (FD100) microcrystalline cellulose during enzymatic digestion. Digestions were
      performed in either of two modes: a static, quiescent mode or a dynamic mode
      using a stirred suspension recycled through a flow cell. The scattering pattern
      for as-received Avicel in D(2)O buffer is comprised of a low Q power law region
      resulting from the surface fractal character of the microcrystalline fibers and a
      high Q roll-off due to scattering from water-filled nanopores with radii
      approximately 20 A. For digestions in the dynamic mode the high Q roll-off
      decreased in magnitude within approximately 1 h after addition of enzymes,
      whereas in the static digestions no change was observed in the high Q roll-off,
      even after 60 h. These results indicate that only with significant agitation does
      enzyme digestion affect the structure of the nanopores.

PMID- 20041635
TI  - High-level genomic integration, epigenetic changes, and expression of sleeping
      beauty transgene.
AB  - Sleeping Beauty transposon (SB-Tn) has emerged as an important nonviral vector
      for integrating transgenes into mammalian genomes. We report here a novel dual
      fluorescent reporter cis SB-Tn system that permitted nonselective fluorescent
      activated cell sorting for SB-Tn-transduced K562 erythroid cells. Using an
      internal ribosome entry site element, the green fluorescent protein (eGFP) was
      linked to the SB10 transposase gene as an indirect marker for the robust
      expression of SB10 transposase. Flourescence-activated cell sorting (FACS) by
      eGFP resulted in significant enrichment (>60%) of cells exhibiting SB-Tn-mediated
      genomic insertions and long-term expression of a DsRed transgene. The hybrid
      erythroid-specific promoter of DsRed transgene was verified in erythroid or
      megakaryocyte differentiation of K562 cells. Bisulfite-mediated genomic analyses
      identified different DNA methylation patterns between DsRed(+) and DsRed(-) cell
      clones, suggesting a critical role in transgene expression. Moreover, although
      the host genomic copy of the promoter element showed no CpG methylation, the same
      sequence carried by the transgene was markedly hypermethylated. Additional
      evidence also suggested a role for histone deacetylation in the regulation of
      DsRed transgene. The presence of SB transgene affected the expression of
      neighboring host genes at distances >45 kb. Our data suggested that a fluorescent
      reporter cis SB-Tn system can be used to enrich mammalian cells harboring SB
      mediated transgene insertions. The observed epigenetic changes also demonstrated
      that transgenes inserted by SB could be selectively modified by endogenous
      factors. In addition, long-range activation of host genes must now be recognized
      as a potential consequence of an inserted transgene cassette containing enhancer
      elements.

PMID- 20041637
TI  - Bis- and trisindolylmethanes (BIMs and TIMs).

PMID- 20041638
TI  - X-ray absorption and X-ray photoelectron spectroscopic study of arsenic
      mobilization during mackinawite (FeS) oxidation.
AB  - In this study we investigated the speciation of the solid-phase As formed by
      reacting 2 x 10(-4) M As(III) with 1.0 g/L mackinawite and the potential for
      these sorbed species to be mobilized (released into the aqueous phase) upon
      exposure to atmospheric oxygen at pH 4.9, 7.1, and 9.1. Before oxygen exposure, X
      ray absorption spectroscopy (XAS) and X-ray photoelectron spectroscopy (XPS)
      analyses indicated that As(III) was removed from the aqueous phase by forming
      As(0), AsS, and surface precipitates as thioarsenites at pH 4.9 and As(0) and
      thioarsenite surface precipitates at pH 7.1 and 9.1. When oxygen was introduced,
      XAS analysis indicated that As(0) and the surface precipitates were quickly
      transformed, whereas AsS was persistent. During intermediate oxygen exposure
      times, dissolved As increased at pH 4.9 and 7.1 due to the rapid oxidation of
      As(0) and the slow precipitation of iron (oxyhydr)oxides, the oxidation products
      of mackinawite. This indicates that oxidative mobilization is a potential pathway
      for arsenic contamination of water at acidic to neutral pH. The mobilized As was
      eventually resorbed by forming edge-sharing and double-corner-sharing surface
      complexes with iron (oxyhydr)oxides.

PMID- 20041640
TI  - Surface potentials in Langmuir monolayers of unidirectionally oriented alpha
      helical diblock copolypeptides.
AB  - The surface potentials and effective dipole moments of alpha-helical amphiphilic
      diblock copolypeptides during monolayer compression at the air-water interface
      are reported. Amphiphilic diblock copolypeptides (PLGA-b-PMLGSLGs) of poly(alpha
      L-glutamic acid) (PLGA) and poly(gamma-methyl-L-glutamate-ran-gamma-stearyl-L
      glutamate) with 30 mol % of stearyl substituents (PMLGSLG) of various block
      lengths were studied during the double-brush formation process at the water
      surface. Upon monolayer spreading of PLGA-b-PMLGSLGs, surface potentials of
      hundreds of millivolts were recorded, attributed to the dipole moments of water
      molecules reorienting due to interactions with the monolayers. Upon compression,
      the effective dipole moments derived from the surface potentials of the PLGA-b
      PMLGSLG monolayers decrease gradually, most likely as a result of the immersion
      of the hydrophilic block in water and cancellation of the interactions between
      the hydrophobic block and the underlying water molecules. The polypeptide
      macrodipole moment immersed in water was apparently effectively screened out. The
      remaining effective dipole moment of the monolayer contributes mainly to the
      hydrophobic block, and upon tilting away from the water surface toward the
      surface normal, it was found to increase with the hydrophobic block length,
      indicating the gradual formation of unidirectional aligned polypeptide molecules
      in the double-brush monolayer.

PMID- 20041639
TI  - Determination of penetratin secondary structure in live cells with Raman
      microscopy.
AB  - Cell penetrating peptides (CPPs) have attracted recent interest as drug delivery
      tools, although the mechanisms by which CPPs are internalized by cells are not
      well-defined. Here, we report a new experimental approach for the detection and
      secondary structure determination of CPPs in live cells using Raman microscopy
      with heavy isotope labeling of the peptide. As a first demonstration of
      principle, penetratin, a 16-residue CPP derived from the Antennapedia homeodomain
      protein of Drosophila, was measured in single, living melanoma cells. Carbon-13
      labeling of the Phe residue of penetratin was used to shift the intense aromatic
      ring-breathing vibrational mode from 1003 to 967 cm(-1), thereby enabling the
      peptide to be traced in cells. Difference spectroscopy and principal components
      analysis (PCA) were used independently to resolve the Raman spectrum of the
      peptide from the background cellular Raman signals. On the basis of the position
      of the amide I vibrational band in the Raman spectra, the secondary structure of
      the peptide was found to be mainly random coil and beta-strand in the cytoplasm,
      and possibly assembling as beta-sheets in the nucleus. The rapid entry and almost
      uniform cellular distribution of the peptide, as well as the lack of correlation
      between peptide and lipid Raman signatures, indicated that the mechanism of
      internalization under the conditions of study was probably nonendocytotic. This
      experimental approach can be used to study a wide variety of CPPs as well as
      other classes of peptides in living cells.

PMID- 20041643
TI  - Synthesis and reactivity of iron acyl complexes modeling the active site of [Fe]
      hydrogenase.
AB  - A [Fe(II)Fe(II)] dithiolate complex containing acyl and carbonyl ligands was
      synthesized. The diiron complex reacted with phosphine, cyanide, isocyanide, and
      CO to give monomeric Fe(II) complexes reproducing the first coordination sphere
      of the active site of [Fe]-hydrogenase (H(2)-forming methylene
      tetrahydromethanopterin dehydrogenase, Hmd) in various states. All the acyl and
      carbonyl carbons in the diiron complex underwent facile isotopic exchange with
      (13)CO via monomeric Fe tricarbonyl intermediates.

PMID- 20041641
TI  - High-resolution solid-state NMR structure of a 17.6 kDa protein.
AB  - The use of pseudocontact shifts arising from paramagnetic metal ions in a
      microcrystalline protein sample is proposed as a strategy to obtain unambiguous
      signal assignments in solid-state NMR spectra enabling distance extraction for
      protein structure calculation. With this strategy, 777 unambiguous (281
      sequential, 217 medium-range, and 279 long-range) distance restraints could be
      obtained from PDSD, DARR, CHHC, and the recently introduced PAR and PAIN-CP solid
      state experiments for the cobalt(II)-substituted catalytic domain of matrix
      metalloproteinase 12 (159 amino acids, 17.6 kDa). The obtained structure is a
      high resolution one, with backbone rmsd of 1.0 +/- 0.2 A, and is in good
      agreement with the X-ray structure (rmsd to X-ray 1.3 A). The proposed strategy,
      which may be generalized for nonmetalloproteins with the use of paramagnetic
      tags, represents a significant step ahead in protein structure determination
      using solid-state NMR.

PMID- 20041644
TI  - Formation of fumonisin B(1)-glucose reaction product, in vitro cytotoxicity, and
      lipid peroxidation on kidney cells.
AB  - Fumonisin B(1) (FB(1)) content in corn products decreases during the heating
      process in foods containing reducing sugars, mainly because of the formation of N
      (carboxymethyl)fumonisin B(1). In this study, a rapid method has been developed
      for the determination of both compounds in corn products using a high-speed
      blender, Ultra-Turrax, for solvent extraction and liquid chromatography-tandem
      mass spectrometry. The kinetics of FB(1) degradation and the formation of the
      Maillard adduct were studied in a model system constituted by corn bread spiked
      with FB(1) and heated at 160, 180, and 200 degrees C for 3, 6, 10, 15, and 20
      min. FB(1) decreased from 0.96 to 0.3 mg/kg and N-(carboxymethyl)fumonisin B(1)
      increased to 0.1 mg/kg. Cytotoxicity and lipid peroxidation were studied in
      monkey kidney cells (Vero cells). After 24 h exposure, FB(1) revealed an IC(50)
      (median inhibitory concentration) of 55 +/- 7 microM with neutral red uptake, but
      no IC(50) was obtained after N-(carboxymethyl)fumonisin B(1) exposure at the
      studied concentrations. Lipid peroxidation was assessed using the thiobarbituric
      acid reactive substance (TBARS) method for 90 min and 24 and 48 h. FB(1)
      significantly increased the production of malondialdehyde in Vero cells exposed
      to 1 microM FB(1) after 24 h, while malondialdehyde increased after 5 microM N
      (carboxymethyl)fumonisin B(1) exposure. These findings showed that the
      transformation products exhibit lower cytotoxicity than fumonisin B(1) and lipid
      peroxidation may be involved in the cytotoxicity induced by both toxins.

PMID- 20041645
TI  - Jahn-Teller distorted frameworks and magnetic order in the Rb-Mn-P-O system.
AB  - Two previously uncharacterized members of the Rb-Mn-P-O system, RbMnP(2)O(7) and
      beta-RbMnHP(3)O(10), have been synthesized using a phosphoric acid flux synthetic
      route and their crystal and magnetic structures determined using neutron powder
      diffraction. The crystal structure of RbMnP(2)O(7) (space group P2(1)/c, a =
      7.3673(2) A, b = 9.6783(2) A, c = 8.6467(2) A, and beta = 105.487(1) degrees) was
      found to be isostructural with RbFeP(2)O(7). The polymorph beta-RbMnHP(3)O(10)
      was also isolated as a single phase and found to crystallize in the space group
      C2 (a = 12.2066(5) A, b = 8.5243(3) A, c = 8.8530(4) A, beta = 107.233(2)
      degrees). Both structures consist of frameworks of corner-sharing MnO(6)
      octahedra linked together by condensed phosphate anions, with Rb(+) cations
      located in the intersecting channels. In both cases the Mn(3+) octahedra exhibit
      unusual Jahn-Teller distortions indicative of a plasticity effect driven by the
      steric requirements of the condensed phosphate anions, and this causes a strong
      violet coloration similar to that observed in the manganese violet pigment; the
      structure of this has yet to be determined. Magnetic susceptibility measurements
      show that both RbMnP(2)O(7) (T(N) = 20 K) and beta-RbMnHP(3)O(10) (T(N) = 10 K)
      undergo a phase transition at low temperatures to an antiferromagnetically
      ordered state. Low-temperature neutron powder diffraction studies show that the
      magnetic ground states of each of these materials involve both ferromagnetic and
      antiferromagnetic super-superexchange interactions between orbitally ordered
      Mn(3+), which are mediated by PO(4) tetrahedra. These interactions are compared
      and discussed.

PMID- 20041646
TI  - Asymmetric synthesis of functionalized 1,3-diphosphines via chiral palladium
      complex promoted hydrophosphination of activated olefins.
AB  - Aldehyde, ester- and keto-functionalized monophosphine palladium complexes
      containing the ortho-metalated (R)-(1-(dimethylamino)ethyl)naphthalene as the
      chiral auxiliary and reaction promoter were synthesized via hydrophosphination of
      acrolein and the subsequent Wittig reactions in a one-pot process. Under very
      mild conditions, the second-stage hydrophosphination of the monophosphine
      substrates gave the corresponding ester-, keto-, and hydroxyl-functionalized
      chiral 1,3-bis(diphenylphosphino)propane palladium complexes with good yields and
      stereoselectivities. The coordination properties and absolute configurations of
      the novel 1,3-diphosphine complexes were established by single crystal X-ray
      crystallography. The enantiomerically pure functionalized diphosphine ligands
      with ester and keto functionalities could be subsequently liberated
      stereospecifically by treatment of the corresponding dichloro palladium complexes
      with aqueous potassium cyanide in high yields.

PMID- 20041647
TI  - Interconversion of perovskite and fluorite structures in Ce-Sc-O system.
AB  - CeScO(3) was synthesized by a two-step synthesis route involving a combustion
      method followed by vacuum heating at 1100 degrees C in the presence of Zr sponge
      which acts as an oxygen getter. The compound was characterized by various
      techniques such as X-ray diffraction (XRD), high temperature XRD,
      thermogravimetry, diffuse reflectance (DR)-UV visible spectrophotometry, and
      Raman spectroscopy. Fluorite-type (F-type) solid solution with composition
      Ce(0.5)Sc(0.5)O(1.75) was observed as an intermediate during the synthesis of
      CeScO(3). Only by mere redox reaction was a reversible transformation between
      fluorite-type structure and perovskites structure observed. CeScO(3) was found as
      semiconducting oxide with band gap of 3.2 eV arising mainly between O p states in
      the valence band and Sc d and Ce d states in the conduction band with small
      contributions coming from Ce f and Sc p states. First-principles potential plane
      wave-based calculations were performed for the band gap and its origin in
      CeScO(3). Photoluminescence measurement showed that CeScO(3) is a potential host
      material giving broad blue emission. This was further confirmed by demonstrating
      CeScO(3) doped with 2 mol % Tb(3+) compound as an efficient green light emitter.

PMID- 20041649
TI  - Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites
      by humans.
AB  - Following the ingestion of green tea, substantial quantities of flavan-3-ols pass
      from the small to the large intestine (Stalmach et al. Mol. Nutr. Food Res. 2009,
      53, S44-S53; Mol. Nutr. Food Res. 2009, doi: 10.1002/mnfr.200900194). To
      investigate the fate of the flavan-3-ols entering the large intestine, where they
      are subjected to the action of the colonic microflora, (-)-epicatechin, (-)
      epigallocatechin, and (-)-epigallocatechin-3-O-gallate were incubated in vitro
      with fecal slurries and the production of phenolic acid catabolites was
      determined by GC-MS. In addition, urinary excretion of phenolic catabolites was
      investigated over a 24 h period after ingestion of either green tea or water by
      healthy volunteers with a functioning colon. The green tea was also fed to
      ileostomists, and 0-24 h urinary excretion of phenolic acid catabolites was
      monitored. Pathways are proposed for the degradation of green tea flavan-3-ols in
      the colon and further catabolism of phenolic compounds passing into the
      circulatory system from the large intestine, prior to urinary excretion in
      quantities corresponding to ca. 40% of intake compared with ca. 8% absorption of
      flavan-3-ol methyl, glucuronide, and sulfate metabolites in the small intestine.
      The data obtained point to the importance of the colonic microflora in the
      overall bioavailability and potential bioactivity of dietary flavonoids.

PMID- 20041651
TI  - Halogens in the troposphere.
AB  - Although inorganic halogen gases are believed to play key roles in the chemistry
      of the lower atmosphere, many of them have not yet been detected or measured in
      ambient air. This article describes some of the current techniques and future
      needs for inorganic halogens in air. (To listen to a podcast about this feature,
      please go to the Analytical Chemistry multimedia page at
      pubs.acs.org/page/ancham/audio/index.html.).

PMID- 20041650
TI  - Inhibition of hypoxia inducible factor 1-transcription coactivator interaction by
      a hydrogen bond surrogate alpha-helix.
AB  - Designed ligands that inhibit hypoxia-inducible gene expression could offer new
      tools for genomic research and, potentially, drug discovery efforts for the
      treatment of neovascularization in cancers. We report a stabilized alpha-helix
      designed to target the binding interface between the C-terminal transactivation
      domain (C-TAD) of hypoxia-inducible factor 1alpha (HIF-1alpha) and cysteine
      histidine rich region (CH1) of transcriptional coactivator CBP/p300. The
      synthetic helix disrupts the structure and function of this complex, resulting in
      a rapid downregulation of two hypoxia-inducible genes (VEGF and GLUT1) in cell
      culture.

PMID- 20041652
TI  - Identification of cows treated with recombinant bovine somatotropin.
AB  - A method for the specific detection and quantification of recombinant bovine
      somatotropin (rbST) in bovine blood has been validated according to criteria
      described in the EU Commission Decision 2002/657/EC. The method is based on a
      thorough purification procedure followed with the detection by LC-ESI-MS/MS of
      the tryptic N-terminal peptide specific of the rbST. The recombinant equine
      somatotropin (reST) is used as internal standard. Performance of the method was
      assessed based on specificity, linearity, trueness and repeatability. Decision
      limit (CCalpha) and detection capability (CCbeta) were found to be 2.5 ng mL(-1)
      and 6.8 ng mL(-1), respectively. This method was subsequently applied to the
      analysis of serum and plasma collected from two different animals treated with
      500 mg of rbST. No significant variations were observed when analyzing either
      serum or plasma, but an important difference between animals was encountered. In
      all cases, recombinant bovine somatotropin was still detected two weeks after
      administration.

PMID- 20041653
TI  - Effects of illicit dexamethasone upon hepatic drug metabolizing enzymes and
      related transcription factors mRNAs and their potential use as biomarkers in
      cattle.
AB  - In cattle fattening, the illicit use of growth promoters (GPs) represents a major
      problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used,
      alone or in combination with other steroids or beta-agonists. Recently, GPs were
      shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional
      level; therefore, the effects of two illicit protocols containing DEX (alone or
      together with 17beta-estradiol, 17betaE) upon main cattle liver drug metabolizing
      enzymes (DMEs) mRNAs and related transcription factors were investigated by
      quantitative real time RT-PCR. Eleven genes, out of the 18 considered, were
      significantly modulated by GPs. Corticosteroid-responsive genes did not respond
      univocally, whereas retinoic X receptor alpha (RXRalpha) and estrogen receptor
      alpha (ERalpha) were upregulated depending on the illicit protocol used.
      Nowadays, an increasing interest has been noticed toward the detection of
      biomarkers of response (BMRs) to be used in the screening of GPs misuse in cattle
      farming. In the present study, CYP2B6-like, CYP2E1, glutathione S-transferase A1-
      and sulfotransferase A1-like (GSTA1- and SULT1A1-like) mRNAs were significantly
      modulated regardless of the GP, the illicit protocol, and the animal breed,
      representing promising BMRs. The usefulness of these BMRs needs to be
      characterized more in depth.

PMID- 20041654
TI  - Ceramic microsystem incorporating a microreactor with immobilized biocatalyst for
      enzymatic spectrophotometric assays.
AB  - Low-temperature cofired ceramics (LTCC) technology is a versatile fabrication
      technique used to construct microflow systems. It permits the integration of
      several unitary operations (pretreatment, separation, (bio)chemical reaction, and
      detection stage) of an analytical process in a modular or monolithic way.
      Moreover, because of its compatibility with biological material, LTCC is adequate
      for analytical applications based on enzymatic reactions. Here we present the
      design, construction, and evaluation of a LTCC microfluidic system that
      integrates a microreactor (internal volume, 24.28 microL) with an immobilized
      beta-galactosidase from Escherichia coli (0.479 activity units) and an optical
      flow cell to measure the product of the enzymatic reaction. The enzyme was
      immobilized on a glyoxal-agarose support, maintaining its activity along the time
      of the study. As a proof of concept, the LTCC-beta-galactosidase system was
      tested by measuring the conversion of ortho-nitrophenyl beta-D-galactopyranoside,
      the substrate usually employed for activity determinations. Once packed in a
      monolithically integrated microcolumn, the miniaturized flow system was
      characterized, the operational conditions optimized (flow rate and injection
      volume), and its performance successfully evaluated by determining the beta
      galactosidase substrate concentration at the millimolar level.

PMID- 20041655
TI  - Reactivity theory of transition-metal surfaces: a Bronsted-Evans-Polanyi linear
      activation energy-free-energy analysis.

PMID- 20041656
TI  - Porous phosphorescent coordination polymers for oxygen sensing.
AB  - Phosphorescent cyclometalated iridium tris(2-phenylpyridine) derivatives were
      designed and incorporated into coordination polymers as tricarboxylate bridging
      ligands. Three different crystalline coordination polymers were synthesized using
      a solvothermal technique and were characterized using a variety of methods,
      including single-crystal X-ray diffraction, PXRD, TGA, IR spectroscopy, gas
      adsorption measurements, and luminescence measurements. The coordination polymer
      built from Ir[3-(2-pyridyl)benzoate](3), 1, was found to be highly porous with a
      nitrogen BET surface area of 764 m(2)/g, whereas the coordination polymers built
      from Ir[4-(2-pyridyl)benzoate](3), 2 and 3, were nonporous. The (3)MLCT
      phosphorescence of each of the three coordination polymers was quenched in the
      presence of O(2). However, only 1 showed quick and reversible luminescence
      quenching by oxygen, whereas 2 and 3 exhibited gradual and irreversible
      luminescence quenching by oxygen. The high permanent porosity of 1 allows for
      rapid diffusion of oxygen through the open channels, leading to efficient and
      reversible quenching of the (3)MLCT phosphorescence. This work highlights the
      opportunity of designing highly porous and luminescent coordination polymers for
      sensing other important analytes.

PMID- 20041658
TI  - Influence of syringyl to guaiacyl ratio on the structure of natural and synthetic
      lignins.
AB  - Several kinds of natural woods and isolated lignins with various syringyl to
      guaiacyl (S/G) ratios were subjected to thioacidolysis followed by Raney nickel
      desulfuration to elucidate the relationships between the S/G ratio and the
      interunit linkage types of lignin. Furthermore, enzymatic dehydrogenation
      polymers (DHP) were produced by the Zutropf (gradual monolignol addition) method
      from mixtures of various ratios of coniferyl alcohol and sinapyl alcohol. The
      analysis of DHPs and natural wood lignins exhibited basically a similar tendency.
      The existence of both syringyl and guaiacyl units is effective for producing
      higher amounts of beta-O-4 and 4-O-5 structures, but it lowers the total amount
      of cinnamyl alcohol and aldehyde end groups. The relative frequency of the beta
      beta structure increased, whereas that of beta-5 and 5-5 structures decreased
      with increasing syringyl units.

PMID- 20041659
TI  - Improved synthesis of (3E,6Z,9Z)-1,3,6,9-nonadecatetraene, attraction inhibitor
      of bruce spanworm, Operophtera bruceata, to pheromone traps for monitoring winter
      moth, Operophtera brumata.
AB  - The winter moth, Operophtera brumata (Lepidoptera: Geometridae), is an early
      season defoliator that attacks a wide variety of hardwoods and, in some cases,
      conifers. The insect is native to Europe but has become established in at least
      three areas of North America including southeastern New England. The female
      produced sex attractant pheromone of the winter moth was identified as (3Z,6Z,9Z)
      1,3,6,9-nonadecatetraene (1), which also attracts a native congener, the Bruce
      spanworm, Operophtera bruceata . Dissection, or (for certainty) DNA molecular
      testing, is required to differentiate between males of the two species. Thus, a
      trapping method that is selective for winter moth would be desirable. A geometric
      isomer of the pheromone, (3E,6Z,9Z)-1,3,6,9-nonadecatetraene (2), can reportedly
      inhibit attraction of Bruce spanworm to traps without affecting winter moth
      catch, but use of the pheromone and inhibitor together has not been optimized,
      nor has the synthesis of the inhibitor. This paper presents two new syntheses of
      the inhibitor (3E,6Z,9Z)-1,3,6,9-nonadecatetraene based on the intermediate
      (3Z,6Z)-3,6-hexadecadien-1-ol (4), which has also been utilized in the synthesis
      of the pheromone. The syntheses combine traditional acetylenic chemistry and
      Wittig olefination reactions. In one approach, 2 was synthesized in 80% purity
      (20% being pheromone 1), and in the second, tetraene 2 of 96% purity (and free of
      1) was produced in 25% overall yield from dienol 4. The last method benefitted
      from a refined TEMPO-mediated PhI(OAc)(2) oxidation of 4 and a two-carbon
      homologation of the corresponding aldehyde 7.

PMID- 20041657
TI  - Instability of cholesterol clusters in lipid bilayers and the cholesterol's
      Umbrella effect.
AB  - The instability of cholesterol clusters and the Umbrella effect of cholesterol in
      dipalmitoylphosphatidylcholine (DPPC) and dioleoylphosphatidylcholine (DOPC)
      lipid bilayers were investigated via atomistic molecular dynamics (MD)
      simulation. Cholesterol clusters in phosphatidylcholine (PC) bilayers are found
      to be very unstable and to readily disperse into cholesterol monomers. This
      instability results from the difficulty of the bilayer system in preventing water
      exposure to cholesterol's bulky hydrophobic bodies in a cluster. The system
      responds to artificially arranged cholesterol clusters in several interesting
      manners: (i) cholesterol clusters quickly form a "frustum" shape to reduce water
      penetration between cholesterol headgroups; (ii) many clusters bury themselves
      deeper into the bilayer interior, causing bilayer deformation; and (iii)
      cholesterol fluctuates rapidly, both laterally and vertically, to escape
      clusters. These fluctuations result in the disintegration of clusters and, in one
      incidence, a highly unusual flip-flop event of cholesterol across the DOPC
      bilayer. Our results show that cholesterols have a strong tendency to avoid
      forming clusters in lipid bilayers and that the fundamental cholesterol
      cholesterol interaction is unfavorable. Furthermore, the radial distribution
      functions of cholesterol hydroxyl oxygen to various headgroup atoms of PC reveal
      that the PC headgroups surrounding cholesterol have a clear tendency to reorient
      and to extend toward cholesterol. This reorientation has a layered structure that
      extends 2-3 nm from the cholesterol molecule. This study demonstrates that the
      Umbrella hypothesis is valid in both saturated and unsaturated lipid bilayers.

PMID- 20041660
TI  - Substantially enhanced degradation of hexachlorocyclohexane isomers by a
      microbial consortium on acclimation.
AB  - Widespread contamination of the environment, globally, has been caused by
      extensive and indiscriminate use of hexachlorocyclohexane (HCH) as an insecticide
      since the 1940s, threatening the biota including humans, and there is an urgent
      need to eliminate it, preferably through bioremediation technologies. A gamma-HCH
      degrading microbial consortium was isolated by enrichment of a soil sample from a
      sugar cane field having a long history of technical grade HCH application. On
      acclimation the degrading ability improved substantially. The consortium, which
      took 10 days to degrade 25 microg mL(-1) of gamma-HCH, initially could mineralize
      even 300 microg mL(-1) of the substrate within 108 h on acclimation. With 300
      microg mL(-1) substrate, the rate of degradation, as calculated for the early
      exponential phase, was 216 microg mL(-1) day(-1), the highest reported so far. An
      amount of 400 microg mL(-1) of gamma-HCH, however, was mineralized partially with
      only 78% Cl(-) release. No apparent accumulation of intermediary metabolites was
      observed up to 300 microg mL(-1) substrate, indicating a fast rate of
      mineralization. Aeration, mesophilic temperatures (20-35 degrees C), and near
      neutral pH (6.0-8.0) were favorable conditions for degradation. The presence of
      glucose at 1000 microg mL(-1) retarded the degradation, whereas cellulose and
      sawdust at 1600 microg mL(-1) and glucose at 100 microg mL(-1) did not show any
      marked effect. The consortium also mineralized alpha-, beta-, and delta-HCH
      efficiently. The consortium consisted of nine bacterial strains and a fungal
      strain, and individually they were able to degrade 10 microg mL(-1) of gamma-HCH.
      This mixed culture holds high potential for deployment in bioremediation of HCH
      contaminated soils, waste dumpsites, and water bodies.

PMID- 20041661
TI  - Poly(DL-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate): synthesis,
      characterization, micellization behavior in aqueous solutions, and encapsulation
      of the hydrophobic drug dipyridamole.
AB  - We synthesized a series of well-defined poly(dl-lactide)-b-poly(N,N-dimethylamino
      2-ethyl methacrylate) (PDLLA-b-PDMAEMA) amphiphilic diblock copolymers by
      employing a three-step procedure: (a) ring-opening polymerization (ROP) of dl
      lactide using n-decanol and stannous octoate, Sn(Oct)(2), as the initiating
      system, (b) reaction of the PDLLA hydroxyl end groups with bromoisobutyryl
      bromide, and (c) atom transfer radical polymerization, ATRP, of DMAEMA with the
      newly created bromoisobutyryl initiating site. The aggregation behavior of the
      prepared block copolymers was investigated by dynamic light scattering and zeta
      potential measurements at 25 degrees C in aqueous solutions of different pH
      values. The hydrophobic drug dipyridamole was efficiently incorporated into the
      copolymer aggregates in aqueous solutions of pH 7.40. High partition coefficient
      values were determined by fluorescence spectroscopy.

PMID- 20041662
TI  - (13)C/(12)C analysis of ultra-trace amounts of volatile organic contaminants in
      groundwater by vacuum extraction.
AB  - We developed a method for the vacuum extraction (VacEx) of volatile organic
      compounds (VOCs) from water samples for ultratrace determinations of carbon
      isotopic signatures. Our method permits compound-specific stable carbon isotope
      analysis (CSIA) at VOC concentrations as low as 0.03-1.34 microg/L. VacEx was
      developed to extract and preconcentrate VOCs for subsequent carbon-CSIA by the
      standard technique purge-and-trap (P&T) coupled to an isotope-ratio mass
      spectrometer (IRMS). Even without complete extraction, the delta(13)C signatures
      of VOCs determined by VacEx-P&T-IRMS were in good agreement (deviation <1 per
      thousand) with signatures determined by P&T-IRMS. This indicates that VacEx does
      not cause isotopic discrimination. Limits of quantification (LOQs) for delta(13)C
      analysis were: 0.03-0.06 microg/L for benzene, toluene, o-xylene, m-p-xylene and
      ethylbenzene, 0.09 microg/L for methyl tert-butyl ether (MTBE), and 0.18-0.27
      microg/L for trans-DCE, cis-DCE, TCE and PCE. These are the lowest LOQs reported
      to date for continuous-flow isotope-ratio determinations using a commercially
      available and automated system. To our knowledge, analytical protocols adopted
      from noble gas analysis in water were applied for the first time to determine the
      isotope composition of organic contaminants. We applied VacEx in a field study to
      illustrate how the determination of VOC isotopic signatures at very low
      concentrations opens new avenues in the in situ assessment of these priority
      groundwater pollutants.

PMID- 20041663
TI  - Removal of biocolloids suspended in reclaimed wastewater by injection into a
      fractured aquifer model.
AB  - Two pilot-scale fractured aquifer models (FAMs) consisting of horizontal
      limestone slabs were employed to investigate the removal of biocolloids suspended
      in reclaimed wastewater. To better understand the behavior of real fractured
      aquifers, these FAMs intentionally were not "clean". The fracture apertures were
      randomly spread with soil deposits, and both FAMs were preflooded with reclaimed
      wastewater to simulate the field conditions of the Nardo fractured aquifer in the
      Salento area, Italy, where fractures are not clean due to artificial groundwater
      recharge. One of the FAMs was injected with secondary effluent from a wastewater
      treatment plant collected prior to the chlorination step and the other with
      exactly the same effluent, which was further treated in a commercial membrane
      reactor. Consequently, the organic and pathogen concentrations were considerably
      higher in the secondary effluent than in the membrane reactor effluent. Injected
      wastewater was continuously recirculated. Pathogen removal was greater for the
      secondary wastewater than the cleaner membrane reactor effluent. A simple
      mathematical model was developed to describe fracture clogging. The results
      suggest that the hydraulic conductivity of FAMs can be significantly degraded due
      to retention of viable and inactivated biocolloids suspended in reclaimed
      wastewater.

PMID- 20041664
TI  - Synthesis, structures, and multinuclear NMR spectra of tin(II) and lead(II)
      complexes of tellurium-containing imidodiphosphinate ligands: preparation of two
      morphologies of phase-pure PbTe from a single-source precursor.
AB  - Group 14 metal complexes of heavy chalcogen-centered anions,
      M[(TeP(i)Pr(2))(2)N](2) (5, M = Sn; 6, M = Pb) and M(TeP(i)Pr(2)NP(i)Pr(2)Se)(2)
      (7, M = Sn; 8, M = Pb), were synthesized in 64-89% yields by metathesis of alkali
      metal salts of the ligands with group 14 metal dihalides. Crystallographic
      characterization of the complexes revealed that 5, 6, and 8 engage in
      metal...chalcogen secondary bonds to generate dimers, whereas 7 is monomeric in
      the solid state. Multinuclear ((1)H, (31)P, (77)Se, and (125)Te) solution NMR
      data for these homoleptic complexes evinced dynamic behavior leading to the
      equivalence of the two ligand environments. The Pb(II) complex 6 was utilized as
      a single-source precursor to micrometer-scale lead telluride particles via two
      divergent techniques: aerosol-assisted chemical vapor deposition of the complex
      in THF/CH(2)Cl(2) solution onto glass substrates yielded rectangular prisms,
      while solution injection of 6 in tri-n-octylphosphine onto Si/SiO(2)(100)
      substrates heated to 200-220 degrees C resulted in the formation of wires. PXRD
      and EDX analysis of the products confirmed the phase purity of the PbTe
      materials.

PMID- 20041665
TI  - Hot phonons in an electrically biased graphene constriction.
AB  - Phonon-carrier interactions can have significant impact on device performance.
      They can be probed by measuring the phonon lifetime, which reflects the
      interaction strength of a phonon with other quasi-particles, in particular charge
      carriers as well as its companion phonons. The carrier phonon and phonon-phonon
      contributions to the phonon lifetime can be disentangled from temperature
      dependent studies. Here, we address the importance of phonon-carrier interactions
      in Joule-heated graphene constrictions in order to contribute to the
      understanding of energy dissipation in graphene-based electronic devices. We
      demonstrate that gapless graphene grants electron-phonon interactions uncommon
      significance in particular at low carrier density. In conventional
      semiconductors, the band gap usually prevents the decay of phonons through
      electron-hole generation and also in metals or other semimetals the Fermi
      temperature is excessively large to enter the regime where electron-phonon
      coupling plays such a dominant role as in graphene in the investigated phonon
      temperature regime from 300 to 1600 K.

PMID- 20041666
TI  - Structure, growth kinetics, and ledge flow during vapor-solid-solid growth of
      copper-catalyzed silicon nanowires.
AB  - We use real-time observations of the growth of copper-catalyzed silicon nanowires
      to determine the nanowire growth mechanism directly and to quantify the growth
      kinetics of individual wires. Nanowires were grown in a transmission electron
      microscope using chemical vapor deposition on a copper-coated Si substrate. We
      show that the initial reaction is the formation of a silicide, eta'-Cu(3)Si, and
      that this solid silicide remains on the wire tips during growth so that growth is
      by the vapor-solid-solid mechanism. Individual wire directions and growth rates
      are related to the details of orientation relation and catalyst shape, leading to
      a rich morphology compared to vapor-liquid-solid grown nanowires. Furthermore,
      growth occurs by ledge propagation at the silicide/silicon interface, and the
      ledge propagation kinetics suggest that the solubility of precursor atoms in the
      catalyst is small, which is relevant to the fabrication of abrupt heterojunctions
      in nanowires.

PMID- 20041667
TI  - Synthesis and characterization of iodinated tetrahydroquinolines targeting the G
      protein-coupled estrogen receptor GPR30.
AB  - A series of iodo-substituted tetrahydro-3H-cyclopenta[c]quinolines was
      synthesized as potential targeted imaging agents for the G protein-coupled
      estrogen receptor GPR30. The affinity and specificity of binding to GPR30 versus
      the classical estrogen receptors ER alpha/beta and functional responses
      associated with ligand-binding were determined. Selected iodo-substituted
      tetrahydro-3H-cyclopenta[c]quinolines exhibited IC(50) values lower than 20 nM in
      competitive binding studies with GPR30-expressing human endometrial cancer cells.
      These compounds functioned as antagonists of GPR30 and blocked estrogen-induced
      PI3K activation and calcium mobilization. The tributylstannyl precursors of
      selected compounds were radiolabeled with (125)I using the iodogen method. In
      vivo biodistribution studies in female ovariectomized athymic (NCr) nu/nu mice
      bearing GPR30-expressing human endometrial tumors revealed GPR30-mediated uptake
      of the radiotracer ligands in tumor, adrenal, and reproductive organs.
      Biodistribution and quantitative SPECT/CT studies revealed structurally related
      differences in the pharmacokinetic profiles, target tissue uptake, and metabolism
      of the radiolabeled compounds as well as differences in susceptibility to
      deiodination. The high lipophilicity of the compounds adversely affects the in
      vivo biodistribution and clearance of these radioligands and suggests that
      further optimization of this parameter may lead to improved targeting
      characteristics.

PMID- 20041668
TI  - Optimization of a pipemidic acid autotaxin inhibitor.
AB  - Autotaxin (ATX, NPP2) has recently been shown to be the lysophospholipase D
      responsible for synthesis of the bioactive lipid lysophosphatidic acid (LPA). LPA
      has a well-established role in cancer, and the production of LPA is consistent
      with the cancer-promoting actions of ATX. Increased ATX and LPA receptor
      expression have been found in numerous cancer cell types. The current study has
      combined ligand-based computational approaches (binary quantitative structure
      activity relationship), medicinal chemistry, and experimental enzymatic assays to
      optimize a previously identified small molecule ATX inhibitor, H2L 7905958 (1).
      Seventy prospective analogs were analyzed via computational screening, from which
      30 promising compounds were synthesized and screened to assess efficacy, potency,
      and mechanism of inhibition. This approach has identified four analogs as potent
      as or more potent than the lead. The most potent analog displayed an IC(50) of
      900 nM with respect to ATX-mediated FS-3 hydrolysis with a K(i) of 700 nM, making
      this compound approximately 3-fold more potent than the previously described
      lead.

PMID- 20041670
TI  - Ginkgo biloba and ginkgotoxin.
AB  - Products prepared from Ginkgo biloba are top-selling phytopharmaceuticals
      especially in Europe and major botanical dietary supplements in the United
      States. In European medicine, G. biloba medications are used to improve memory,
      to treat neuronal disorders such as tinnitus or intermittent claudication, and to
      improve brain metabolism and peripheral blood flow. The whole array of
      indications is reflected by a number of defined natural product constituents in
      G. biloba. The most well-known ones are flavonoids and terpene lactones, but they
      also include allergenic and toxic compounds such as ginkgotoxin (1).
      Consequently, there are reports attributing beneficial as well as adverse effects
      to G. biloba products. The present paper summarizes recent experiences with G.
      biloba and its derived products and explains why their restricted use is
      recommended.

PMID- 20041669
TI  - Synthesis of dihydrofuroaporphine derivatives: identification of a potent and
      selective serotonin 5-HT 1A receptor agonist.
AB  - A series of new aporphine analogues were synthesized and pharmacologically
      evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19)
      aporphines displayed the highest affinity at the 5-HT(1A) receptor with K(i)
      values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the
      diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer
      (cis-19). [(35)S]GTP gamma S function assays on 5-HT(1A) receptor indicated that
      aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high
      efficacy full antagonist and cis-19 was a full agonist. The agonistic property of
      cis-19 at the 5-HT(1A) receptor was further confirmed in vitro and in vivo. This
      compound may be useful as a potential treatment for anxiety.

PMID- 20041671
TI  - Ambient large-scale template-mediated synthesis of high-aspect ratio single
      crystalline, chemically doped rare-earth phosphate nanowires for bioimaging.
AB  - A simple and effective template-mediated protocol has been developed for the
      large-scale, room-temperature preparation of high-aspect-ratio, single
      crystalline Tb-doped CePO(4) nanowires, measuring approximately 12 nm in diameter
      and over 10 mum in length. Moreover, we also isolated sheaf-like bundles of
      nanostructures. The synthesis mechanism likely involved a crystal splitting step.
      The resulting nanowires demonstrated an intense redox-sensitive green
      photoluminescence, which was exploited, in addition to their inherently high
      biocompatibility and low toxicity, for potential applications in biological
      imaging and labeling of cells.

PMID- 20041672
TI  - Conjugates of desferrioxamine B (DFOB) with derivatives of adamantane or with
      orally available chelators as potential agents for treating iron overload.
AB  - Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3
      hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid,
      adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1
      pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2
      hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (deferasirox) were prepared and
      the integrity of Fe(III) binding of the compounds was established from
      electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of
      intracellular (59)Fe mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic
      acid adduct was 3-fold greater than DFOB alone, and the IC(50) value of this
      adduct was 6- or 15-fold greater than DFOB in two different cell types. The
      relationship between logP and (59)Fe mobilization for the DFOB conjugates showed
      that maximal mobilization of intracellular (59)Fe occurred at a logP value
      approximately 2.3. This parameter, rather than the affinity for Fe(III), appears
      to influence the extent of intracellular (59)Fe mobilization. The low toxicity
      high Fe mobilization efficacy of selected adamantane-based DFOB conjugates
      underscores the potential of these compounds to treat iron overload disease in
      patients with transfusional-dependent disorders such as beta-thalassemia.

PMID- 20041674
TI  - Stochastic resonance in a generalized quantum Kubo oscillator.
AB  - We discuss stochastic resonance in a biased linear quantum system that is subject
      to multiplicative and additive noises. Starting from a microscopic system
      reservoir Hamiltonian, we derive a c-number analogue of the generalized Langevin
      equation. The developed approach puts forth a quantum mechanical generalization
      of the "Kubo type" oscillator which is a linear system. Such a system is often
      used in the literature to study various phenomena in nonequilibrium systems via a
      particular interaction between system and the external noise. Our analytical
      results proposed here have the ability to reveal the role of external noise and
      vis-a-vis the mechanisms and detection of subtle underlying signatures of the
      stochastic resonance behavior in a linear system. In our development, we show
      that only when the external noise possesses a "finite correlation time" the
      quantum effect begins to appear. We observe that the quantum effect enhances the
      resonance in comparison to the classical one.

PMID- 20041673
TI  - Ion selectivity of alpha-hemolysin with a beta-cyclodextrin adapter. I. Single
      ion potential of mean force and diffusion coefficient.
AB  - The alpha-hemolysin (alphaHL) is a self-assembling exotoxin that binds to the
      membrane of a susceptible host cell and causes its death. Experimental studies
      show that electrically neutral beta-cyclodextrin (betaCD) can insert into the
      alphaHL channel and significantly increase its anion selectivity. To understand
      how betaCD can affect ion selectivity, molecular dynamics simulations and
      potential of mean force (PMF) calculations are carried out for different alphaHL
      channels with and without the betaCD adapter. A multiscale approach based on the
      generalized solvent boundary potential is used to reduce the size of the
      simulated system. The PMF profiles reveal that betaCD has no anion selectivity by
      itself but can increase the Cl(-) selectivity of the alphaHL channel when lodged
      into the pore lumen. Analysis shows that betaCD causes a partial desolvation of
      ions and affects the orientation of nearby charged residues. The ion selectivity
      appears to result from increased electrostatic interaction between the ion and
      the channel due to a reduction in dielectric shielding by the solvent. These
      observations suggest a reasonable explanation of the ion selectivity and provide
      important information for further ion channel modification.

PMID- 20041675
TI  - Fusion of nonionic vesicles.
AB  - We present an experimental study of vesicle fusion using light and neutron
      scattering to monitor fusion events. Vesicles are reproducibly formed with an
      extrusion procedure using an single amphiphile triethylene glycol mono-n-decyl
      ether in water. They show long-term stability for temperatures around 20 degrees
      C, but at temperatures above 26 degrees C we observe an increase in the scattered
      intensity due to fusion. The system is unusually well suited for the study of
      basic mechanisms of vesicle fusion. The vesicles are flexible with a bending
      rigidity of only a few k(B)T. The monolayer spontaneous curvature, H(0), depends
      strongly on temperature in a known way and is thus tunable. For temperatures
      where H(0) > 0 vesicles are long-term stable, while in the range H(0) < 0 the
      fusion rate increases the more negative the spontaneous curvature. Through a
      quantitative analysis of the fusion rate we arrive at a barrier to fusion
      changing from 15 k(B)T at T = 26 degrees C to 10 k(B)T at T = 35 degrees C. These
      results are compatible with the theoretical predictions using the stalk model of
      vesicle fusion.

PMID- 20041676
TI  - Protein adsorption on a hydrophobic surface: a molecular dynamics study of
      lysozyme on graphite.
AB  - Adsorption of human lysozyme on hydrophobic graphite is investigated through
      atomistic computer simulations with molecular mechanics (MM) and molecular
      dynamics (MD) techniques. The chosen strategy follows a simulation protocol
      proposed by the authors to model the initial and the final adsorption stage on a
      bare surface. Adopting an implicit solvent and considering 10 starting molecular
      orientations so that all the main sides of the protein can face the surface, we
      first carry out an energy minimization to investigate the initial adsorption
      stage, and then long MD runs of selected arrangements to follow the surface
      spreading of the protein maximizing its adsorption strength. The results are
      discussed in terms of the kinetics of surface spreading, the interaction energy,
      and the molecular size, considering both the footprint and the final thickness of
      the adsorbed protein. The structural implications of the final adsorption
      geometry for surface aggregation and nanoscale structural organization are also
      pointed out. Further MD runs are carried out in explicit water for the native
      structure and the most stable adsorption state to assess the local stability of
      the geometry obtained in implicit solvent, and to calculate the statistical
      distribution of the water molecules around the whole lysozyme and its backbone.

PMID- 20041677
TI  - Uniform patterning of sub-50-nm-scale Au nanostructures on insulating solid
      substrate via dip-pen nanolithography.
AB  - We report a direct deposition strategy for sub-50-nm-scale uniform Au patterns on
      virtually any general insulating substrate via dip-pen nanolithography (DPN). In
      that process, HAuCl(4) molecules were deposited onto bare insulating substrates
      via a molecular diffusion process, in the absence of electrochemical reactions.
      Subsequently, the generated HAuCl(4) molecular patterns were decomposed to leave
      Au-only patterns using a thermal annealing process. Uniform Au patterns with a
      mean diameter of 47.9 +/- 3.1 nm were achieved after the annealing process. The
      strategy allowed us to generate Au patterns on virtually any general insulating
      substrate (e.g., SiO(2), Al(2)O(3), polyimide, etc) without the need for surface
      functionalization or additional electrode structures. This versatile and reliable
      patterning method is expected to be useful in the future development of various
      novel industrial applications (e.g., mask or nanocircuit repair, nanosensors,
      etc.).

PMID- 20041678
TI  - Aerosol-based self-assembly of nanoparticles into solid or hollow mesospheres.
AB  - The ability to manipulate miniature object assemblies with well-defined
      structures in a controllable manner is of both fundamental and applied interests.
      This article presents general strategies, with nanospheres as building blocks, to
      engineer mesoscopic spherical architectures via a process of evaporation-driven
      self-assembly in aerosol droplets. Uniform magnetite iron oxide (Fe(3)O(4),
      approximately 2.5 nm), silica (SiO(2), approximately 15 nm), and cupric oxide
      (CuO, approximately 6 nm) nanoparticles were employed for the structural
      architecture. The method enables microstructural control of the self-assembled
      mesospheres by tuning the competition between solvent evaporation and solute
      diffusion within an aerosol droplet. Furthermore, we have demonstrated it is
      technically feasible to assemble surface-dissimilar binary components, i.e.,
      charge-stabilized hydrophilic SiO(2) and hydrophobic ligand-capped Fe(3)O(4)
      nanoparticles, into hierarchical composite structures, which could be extended
      for preparation of more hierarchically textured materials with desired
      functionalities.

PMID- 20041679
TI  - Study of the pluronic-silica interaction in synthesis of mesoporous silica under
      mild acidic conditions.
AB  - The interaction between silica and poly(ethylene oxide) (PEO) in water may appear
      trivial and it is generally stated that hydrogen bonding is responsible for the
      attraction. However, a literature search shows that there is not a consensus with
      respect to the mechanism behind the attractive interaction. Several papers claim
      that only hydrogen bonding is not sufficient to explain the binding. The silica
      PEO interaction is interesting from an academic perspective and it is also
      exploited in the preparation of mesoporous silica, a material of considerable
      current interest. This study concerns the very early stage of synthesis of
      mesoporous silica under mild acidic conditions, pH 2-5, and the aim is to shed
      light on the interaction between silica and the PEO-containing structure
      directing agent. The synthesis comprises two steps. An organic silica source,
      tetraethylorthosilicate (TEOS), is first hydrolyzed and Pluronic P123, a
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO)
      block copolymer, is subsequently added at different time periods following the
      hydrolysis of TEOS. It is shown that the interaction between the silica and the
      Pluronic is dependent both on the temperature and on the time between onset of
      TEOS hydrolysis and addition of the copolymer. The results show that the
      interaction is mainly driven by entropy. The effect of the synthesis temperature
      and of the time between hydrolysis and addition of the copolymer on the final
      material is also studied. The material with the highest degree of mesoorder was
      obtained when the reaction was performed at 20 degrees C and the copolymer was
      added 40 h after the start of TEOS hydrolysis. It is claimed that the reason for
      the good ordering of the silica is that whereas particle formation under these
      conditions is fast, the rate of silica condensation is relatively low.

PMID- 20041680
TI  - Instability of confined water films between elastic surfaces.
AB  - We investigated the dynamics of nanometer thin water films at controlled ambient
      humidity adsorbed onto two atomically smooth mica sheets upon rapidly bringing
      the surfaces into contact. Using a surface forces apparatus (SFA) in imaging
      mode, we found that the water films break up into a distribution of drops with a
      typical thickness of a few nanometers and a characteristic lateral size and
      spacing of several micrometers. Whereas the characteristic length is found to be
      independent of the ambient humidity, the characteristic time of the breakup
      decreases from approximately 1 to 0.01 s with increasing humidity. The existence
      of characteristic length and time scales shows that this breakup is controlled by
      an instability rather than a conventional nucleation and growth mechanism for SFA
      experiments. These findings cannot be explained by a dispersion-driven
      instability mechanism. In contrast, a model involving the elastic energies for
      the deformation of both the mica sheets and the underlying glue layer correctly
      reproduces the scaling of the characteristic length and time with humidity.

PMID- 20041681
TI  - Controlled flats on spherical polymer colloids.
AB  - Colloidal particles with heterogeneous surfaces offer rich possibilities for
      controlled self-assembly. We have developed a method for preparing micrometer
      sized polystyrene spheres with circular flat spots of controlled radius and
      location. The flats are created by settling the particles onto a flat glass
      substrate and then raising the temperature above the glass-transition temperature
      of the polymer for a controlled time (t). The polymer particle spreads on the
      glass such that the radius of the flat grows with time. We present a scaling
      theory for the hydrodynamics of the flattening process, finding that the radius
      of the flat grows as t(1/3). The model is in good agreement with our experimental
      observations of the flat radius versus spreading time as well as with previous
      studies in the literature for sintering polymer spheres.

PMID- 20041682
TI  - Self-assembled monolayers of aromatic omega-aminothiols on gold: surface
      chemistry and reactivity.
AB  - Amino-terminated self-assembled monolayers on gold substrates were studied by X
      ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure
      (NEXAFS) measurements, and atomic force microscopy (AFM). Two different omega
      amino-4,4'-terphenyl substituted alkanethiols of the general structure H(2)N
      (C(6)H(4))(3)-(CH(2))(n)-SH (ATPn) were used: 2-(4''-amino-1,1':4',1''-terphenyl
      4-yl)ethane-1-thiol (n = 2, ATP2) and 3-(4''-amino-1,1':4',1''-terphenyl-4
      yl)propane-1-thiol (n = 3, ATP3). Moreover, the addressability of amino groups
      within the films was investigated by chemical derivatization of ATPn SAMs with
      3,5-bis(trifluoromethyl)phenyl isothiocyanate (ITC) forming fluorinated thiourea
      ATPn-F films. Evaluation of high-resolution C 1s and N 1s XPS data revealed
      successful derivatization of at least 50% of surface amino species. Furthermore,
      it could be demonstrated by angle-resolved NEXAFS spectroscopy that chemical
      derivatization with ITC has no noticeable influence on the preferential upright
      orientation of the molecules in the SAMs.

PMID- 20041683
TI  - Automatic column coupling system to operate chromatographic supports closer to
      their kinetic performance limit and to enhance method development.
AB  - A new hardware solution is proposed that allows one to automatically change the
      length of a chromatographic bed. The setup is based on the serial coupling of
      chromatographic columns using two rotor-stator valves (with N positions, N + 1
      ports). Despite the use of a prototype setup requiring rather long connection
      tubing, only 9% loss in efficiency is observed for compounds with a retention
      factor above 4 compared to the efficiency expected on the basis of the individual
      column results. It has been demonstrated for a number of isocratic and gradient
      separations that the system allows one to realize considerable analysis time
      savings by adapting the total column length to the specific sample requirements
      and/or to the stage of method development wherein one is working. During method
      development, a separation on a short column length can first be used to rapidly
      gain insight into the composition of the sample, leaving fewer runs to be done on
      a column of maximal length (offering efficiencies that are inaccessible with
      individual column systems). The ease with which information can be obtained on
      columns of different lengths can furthermore be exploited for screening purposes
      to detect coeluting components in a stage wherein they still appear completely
      unresolved (i.e., have a resolution well below R(s) = 0.5).

PMID- 20041684
TI  - Specific nucleic acid detection using photophysical properties of quantum dot
      probes.
AB  - In the present study, we report a novel separation-free method to detect and
      quantify avian influenza virus A (H5N1) nucleic acid without amplification, based
      on the alteration of photophysical parameters of quantum dot (QD) probes after
      hybridization with specific complementary target DNA. The target DNA was
      quantified in a custom-made portable device by simultaneously measuring lifetime
      and quenching of the QD probes. QD probes (25-mer) showed a 30% lifetime
      reduction and 40% fluorescence quenching when hybridized with complementary 25
      mer target DNA. In comparison with a conventional QD-based assay, this assay
      provides a simple quantitation of nucleic acids with a single labeling step.

PMID- 20041685
TI  - Kinetic and thermodynamic investigation of rhodamine B adsorption at
      solid/solvent interfaces by use of evanescent-wave cavity ring-down spectroscopy.
AB  - Evanescent-wave cavity ring-down spectroscopy is applied to investigate the
      adsorption behavior of rhodamine B at three different interfaces. The adsorption
      equilibrium constant (K(ads)) and adsorption free energy of rhodamine B at the
      silica/methanol interface are determined to be (1.5 +/- 0.2) x 10(4) M(-1) and 
      23.8 +/- 0.4 kJ/mol by use of a Langmuir isotherm model. A Langmuir-based kinetic
      model is also developed to determine the corresponding adsorption and desorption
      rate constants of (1.02 +/- 0.03) x 10(2) M(-1) s(-1) and (7.1 +/- 0.2) x 10(-3)
      s(-1), from which K(ads) is obtained to be (1.45 +/- 0.09) x 10(4) M(-1), in
      agreement with the value determined under equilibrium conditions. Similarly, when
      rhodamine B is at the chlorotrimethylsilane-immobilized silica/methanol
      interface, the adsorption and desorption rate constants are determined to be (1.7
      +/- 0.2) x 10(2) M(-1) s(-1) and (5.0 +/- 1.0) x 10(-3) s(-1). The subsequent
      K(ads) is (3.6 +/- 0.4) x 10(4) M(-1), which is larger than that at the
      silica/methanol interface. The former adsorption is dominated by hydrophobic
      interaction, while the latter is subject to electrostatic attraction. When
      rhodamine B is at the silica/water interface, there exist three chemical forms,
      including zwitterion (R(+)B(-)), cation (RBH(+)), and lactone (RBL). A
      combination of double-layer and Langmuir competitive models is used to fit the
      adsorption isotherm as a function of solution pH, yielding K(ads) of (2.5 +/-
      0.2) x 10(4) M(-1) and (1.1 +/- 0.2) x 10(5) M(-1) for R(+)B(-) and RBH(+),
      respectively. RBL is considered to have the same K(ads) value as R(+)B(-).

PMID- 20041686
TI  - Discovery of 3-formyl-tyrosine metabolites from Pseudoalteromonas tunicata
      through heterologous expression.
AB  - Genome mining and identification of natural product gene clusters typically
      relies on the presence of canonical nonribosomal polypeptide synthetase (NRPS) or
      polyketide synthase (PKS) domains. Recently, other condensation enzymes, such as
      the ATP-grasp ligases, have been recognized as important players in natural
      product biosynthesis. In this study, sequence based searching for homologues of
      DdaF, the ATP-grasp amide ligase from dapdiamide biosynthesis, led to the
      identification of a previously unannotated biosynthetic gene cluster in
      Pseudoalteromonas tunicata. Heterologous expression of the cluster in Escherichia
      coli allowed for the production and structure determination of two new 3-formyl
      tyrosine metabolites.

PMID- 20041687
TI  - Imaging different interactions of mercury and silver with live cells by a
      designed fluorescence probe rhodamine B selenolactone.
AB  - Rhodamine B selenolactone has been designed, synthesized, and characterized as a
      new fluorescent probe for imaging both Hg(2+) and Ag(+) in live cells to better
      understand their distinct toxicities to organisms. The probe is designed based on
      the fact that selenium has a strong affinity for mercury and silver, and is
      constructed by incorporating a Se atom into the spirocyclic structure of
      rhodamine. It exhibits a rapid and specific spectroscopic off-on response to
      Hg(2+) and Ag(+) instead of other species, with detection limits of 23 nM Hg(2+)
      and 52 nM Ag(+). Moreover, the probe is membrane-permeable, and can react with
      Ag(+) even in the presence of Cl(-) because of the higher affinity of Se than Cl(
      ) for Ag(+), which makes it of potential use for imaging not only Hg(2+) but also
      Ag(+) in live cells. This applicability has been demonstrated by imaging Hg(2+)
      and Ag(+) in Hela cells. It is observed that the reaction of Ag(+) with the probe
      inside the cells occurs much slower than that of Hg(2+), which is ascribed to the
      high concentration of cellular chloride ions inhibiting the formation of
      sufficient free Ag(+). The present finding is helpful to get an insight into the
      different interaction mechanism of Hg(2+) and Ag(+) with cells, and more
      applications of the probe may be expected for studying the behaviors of Hg(2+)
      and Ag(+) in various biosystems.

PMID- 20041688
TI  - Conformationally gated fragmentations and rearrangements promoted by interception
      of the Bergman cyclization through intramolecular H-abstraction: a possible
      mechanism of auto-resistance to natural enediyne antibiotics?
AB  - A variety of fragmentations and rearrangements can follow Bergman cyclization in
      enediynes equipped with acetal rings mimicking the carbohydrate moiety of natural
      enediyne antibiotics of the esperamicine and calchiamicine families. In the first
      step of all these processes, intramolecular H-atom abstraction efficiently
      intercepts the p-benzyne product of the Bergman cyclization through a six
      membered TS and transforms the p-benzyne into a new more stable radical.
      Depending on the substitution pattern and reaction conditions, this radical
      follows four alternative paths: (a) abstraction of an external hydrogen atom, (b)
      O-neophyl rearrangement which transposes O- and C-atoms of the substituent, (c)
      fragmentation of the O-C bond in the acetal ring, or (d) fragmentation with
      elimination of the appended acetal moiety as a whole. Experiments with varying
      concentrations of external H-atom donor (1,4-cyclohexadiene) were performed to
      gain further insight into the competition between intermolecular H-abstraction
      and the fragmentations. The Thorpe-Ingold effect in gem-dimethyl substituted
      enediynes enhances the efficiency of fragmentation to the extent where it cannot
      be prevented even by a large excess of external H-atom donor. These processes
      provide insight into a possible mechanism of unusual fragmentation of esperamicin
      A(1) upon its Bergman cycloaromatization and lay foundation for a new approach
      for the conformational control of reactivity of these natural antitumor
      antibiotics. Such an approach, in conjunction with supramolecular constraints,
      may provide a plausible mechanism for resistance to enediyne antibiotics by the
      enediyne-producing microorganisms.

PMID- 20041689
TI  - Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases.
AB  - Construction of a genomic DNA library from Pantoea agglomerans strain CU0119 and
      screening against the plant pathogen Erwinia amylovora yielded a new family of
      antibiotics, dapdiamides A-E (1-5). The structures were established through 2D
      NMR experiments and mass spectrometry, as well as the synthesis of dapdiamide A
      (1). Transposon mutagenesis of the active cosmid allowed identification of the
      biosynthetic gene cluster. The dapdiamide family's promiscuous biosynthetic
      pathway contains two unconventional amide ligases that are predicted to couple
      its constituent monomers.

PMID- 20041690
TI  - Prospects for making organometallic compounds with BF ligands: fluoroborylene
      iron carbonyls.
AB  - The fluoroborylene ligand (BF), isoelectronic with CO, was recently (2009)
      realized experimentally by Vidovic and Aldridge in Cp(2)Ru(2)(CO)(4)(mu-BF). In
      this research the related iron carbonyl fluoroborylene complexes Fe(BF)(CO)(n) (n
      = 4, 3), Fe(2)(BF)(CO)(8), and Fe(2)(BF)(2)(CO)(n) (n = 7, 6) are compared with
      the isoelectronic Fe(CO)(n+1) and Fe(2)(CO)(n+2) as well as the thiocarbonyls
      Fe(CS)(CO)(n) and Fe(2)(CS)(2)(CO)(n) using density functional theory. For
      Fe(BF)(CO)(4) the axially and equatorially substituted trigonal bipyramidal
      structures are predicted to be nearly degenerate as is the case for
      Fe(CS)(CO)(4). The lowest energy structures for Fe(BF)(CO)(3) are derived from
      the trigonal bipyramidal Fe(BF)(CO)(4) structures by removal of CO groups. For
      the binuclear derivatives Fe(2)(BF)(CO)(8) and Fe(2)(BF)(2)(CO)(n) (n = 7, 6)
      structures with BF bridges are preferred energetically over structures with CO
      bridges. However, no structures for the unsaturated Fe(2)(BF)(2)(CO)(6) are found
      with four-electron donor eta(2)-mu-BF groups. This differs from the corresponding
      Fe(2)(CS)(2)(CO)(6) where structures with eta(2)-mu-CS groups and formal Fe-Fe
      single bonds are preferred over structures with only two electron donor CO and CS
      groups and formal Fe=Fe double bonds. The lowest energy structure for
      Fe(2)(BF)(2)(CO)(7) is thus predicted to be similar to the well-known triply
      bridged Fe(2)(CO)(9) structure but with two bridging BF groups and one bridging
      CO group. However, the dissociation energy of Fe(2)(BF)(2)(CO)(7) into
      mononuclear fragments is much higher than that of Fe(2)(CO)(9). Removal of the
      bridging CO group from this lowest energy Fe(2)(BF)(2)(CO)(7) structure leads to
      the doubly BF-bridged global minimum structure for Fe(2)(BF)(2)(CO)(6).

PMID- 20041691
TI  - Trends in substrate hydroxylation reactions by heme and nonheme iron(IV)-oxo
      oxidants give correlations between intrinsic properties of the oxidant with
      barrier height.
AB  - Iron(IV)-oxo species have been characterized in several nonheme enzymes and
      biomimetic systems and are efficient oxidants of aliphatic hydroxylation
      reactions. However, there appears to be a large variation in substrate
      hydroxylation ability by different iron(IV)-oxo oxidants due to the effect of the
      ligands bound to the metal. In this work, we have studied these indirect effects
      of ligands perpendicular (cis or equatorial) and opposite (trans or axial) to the
      iron(IV)-oxo group in heme and nonheme oxidants on the oxygenation capability of
      the oxidant. To this end, we have done a series of density functional theory
      calculations on the hydrogen atom abstraction of propene by a range of different
      iron(IV)-oxo oxidants that include heme and nonheme iron(IV)-oxo oxidants. We
      show that the hydrogen atom abstraction barrier of substrate hydroxylation
      correlates linearly with the strength of the Fe(III)O-H bond that is formed,
      i.e., BDE(OH), and that this value ranges by at least 20 kcal mol(-1) dependent
      on the cis- and trans-ligands attached to the metal. Thus, our studies show that
      ligands bound to the metal are noninnocent and influence the catalytic properties
      of the metal-oxo group dramatically due to involvement into the high-lying
      occupied and virtual orbitals. A general valence bond curve crossing model is set
      up that explains how the rate constant of hydrogen atom abstraction is
      proportional to the difference in energy of the C-H bond of the substrate that is
      broken and the O-H bond of the Fe(III)O-H complex that is formed, i.e.,
      proportional to BDE(CH) - BDE(OH) or the reaction enthalpy. In addition, we show
      a correlation between the polarizability change and barrier height for the
      hydrogen atom abstraction reaction.

PMID- 20041692
TI  - Spectroscopic investigation of the multiphoton photolysis reactions of
      bromomethanes (CHBr3, CHBr2Cl, CHBrCl2, and CH2Br2) at near-ultraviolet
      wavelengths.
AB  - Nascent emission and laser-induced dispersed fluorescence spectra of products or
      intermediates from the multiphoton photolysis reaction of bromomethanes (CHBr(3),
      CHBr(2)Cl, CHBrCl(2), and CH(2)Br(2)) at 266 nm were recorded in a slow flow
      cell. Electronically excited species including CH (A(2)Delta, B(2)Sigma(-), and
      C(2)Sigma(+)), C(2) (d(3)Pi(g)), and atomic Br ((4)D(J) and (4)P(J)) were
      observed in the nascent emission spectra. Free radicals such CHBr or CHCl were
      also successfully found using laser-induced dispersed fluorescence spectroscopy.
      The reactive intermediate, CHBr, was seen only in the photolysis of CHBr(3),
      whereas CHCl was only discovered when the precursor was CHBr(2)Cl or CHBrCl(2).
      More experiments including the power dependence and temporal waveform
      measurements were conducted. The present study reports the first direct
      measurements of the intermediate products in the multiphoton photodissociation
      reaction of these bromomethanes at 266 nm. Nascent emission spectra following the
      photolysis at longer near-ultraviolet wavelengths (280 and 355 nm) were also
      acquired. On the bassis of these results, the multiphoton photodissociation
      mechanism of these bromomethanes at 266 nm can be confirmed.

PMID- 20041695
TI  - 6Li diffusion-ordered NMR spectroscopy (DOSY) and applications to organometallic
      complexes.
AB  - The development of (6)Li diffusion-ordered NMR spectroscopy (DOSY) is reported.
      This technique is applied to (6)Li organometallic complexes. (6)Li DOSY provides
      a facile means of identification of peaks in the (6)Li spectrum, as well as
      evidence of mixed aggregates based on relative diffusion coefficients. (6)Li data
      is correlated to (1)H diffusion experiments through (6)Li{(1)H} HOESY and/or
      (1)H{(6)Li} HMBC experiments to obtain formula weight information of Li
      aggregates.

PMID- 20041696
TI  - Selective activation of alkanes by gas-phase metal ions.

PMID- 20041697
TI  - Investigation of complementary reactions of a dipyrromethane with a
      dipyrromethanemonocarbinol leading to a 5-isocorrole.
AB  - Two complementary dipyrromethane + dipyrromethanemonocarbinol routes to a meso
      substituted 5-isocorrole were investigated. While both routes could afford the
      identical 5-isocorrole, self-condensation of the different
      dipyrromethanemonocarbinol precursors could potentially lead to a second
      porphyrinoid of different structure (a porphyrin or a porphodimethene). The two
      reaction routes were examined to compare the distribution of porphyrinoid
      products, probe the effect of key reaction parameters on the product
      distribution, and identify conditions for the efficient preparation of the 5
      isocorrole so that its spectral properties and stability toward light and air
      could be assessed. For each route, a systematic survey of reaction parameters was
      performed via analytical-scale reactions monitored for the yields of the 5
      isocorrole and self-condensation product by HPLC. The two reaction routes were
      found to afford very different product distributions in accordance with the
      anticipated nucleophilicity of the dipyrromethane and dipyrromethanemonocarbinol
      precursors. The most promising reaction condition (InCl(3), 0.32 mM) was
      performed on a preparative-scale providing the 5-isocorrole in an isolated yield
      of 31% (102 mg). Spectroscopic analysis was consistent with the 5-isocorrole
      structure. The stability of the 5-isocorrole in dilute solution upon exposure to
      light and air was assessed by UV-vis spectroscopy and HPLC and was found to be
      excellent.

PMID- 20041693
TI  - Differential phospholipid binding of alpha-synuclein variants implicated in
      Parkinson's disease revealed by solution NMR spectroscopy.
AB  - Three familial variants of the presynaptic protein alpha-synuclein (alphaS),
      A30P, E46K, and A53T, correlate with rare inherited Parkinson's disease (PD),
      while wild-type alphaS is implicated in sporadic PD. The classic manifestation of
      both familiar and sporadic PD is the formation of fibrillar structures of alphaS
      which accumulate as the main component in intraneuronal Lewy bodies. At
      presynaptic termini, the partitioning of alphaS between disordered cytosolic and
      membrane-bound states likely mediates its proposed role in regulation of reserve
      pools of synaptic vesicles. Previously, we reported on multiple distinct
      phospholipid binding modes of alphaS with slow binding kinetics. Here, we report
      the phospholipid binding properties of the disease variants, viewed by solution
      NMR in a residue-specific manner. Our results agree qualitatively with previous
      biophysical studies citing overall decreased lipid affinity for the A30P
      mutation, comparable affinity for A53T, and an increased level of binding of
      E46K, relative to wild-type alphaS. Additionally, our NMR results describe the
      distribution of lipid-bound states for alphaS: the population of the SL1 binding
      mode (residues 3-25 bound as a helix) is augmented by each of the disease
      variants, relative to wild-type alphaS. We propose that the SL1 binding mode,
      which anchors the N-terminus of alphaS in the lipoprotein complex while the
      hydrophobic NAC region remains dynamically disordered, is prone to intermolecular
      interactions which progress toward disease-associated oligomers and fibrils. The
      elevation of the SL1 binding mode, unchecked by a proportionate population of
      binding modes incorporating the full N-terminal domain, may well account for the
      increased toxicity of the A30P, E46K, and A53T disease variants of alphaS.

PMID- 20041698
TI  - Tunable Kondo effect in a single donor atom.
AB  - The Kondo effect has been observed in a single gate-tunable atom. The measurement
      device consists of a single As dopant incorporated in a silicon nanostructure.
      The atomic orbitals of the dopant are tunable by the gate electric field. When
      they are tuned such that the ground state of the atomic system becomes a (nearly)
      degenerate superposition of two of the silicon valleys, an exotic and hitherto
      unobserved valley Kondo effect appears. Together with the "regular" spin Kondo,
      the tunable valley Kondo effect allows for reversible electrical control over the
      symmetry of the Kondo ground state from an SU(2) to an SU(4) configuration.

PMID- 20041699
TI  - A hybrid nanosensor for TNT vapor detection.
AB  - Real-time detection of trace chemicals, such as explosives, in a complex
      environment containing various interferents has been a difficult challenge. We
      describe here a hybrid nanosensor based on the electrochemical reduction of TNT
      and the interaction of the reduction products with conducting polymer
      nanojunctions in an ionic liquid. The sensor simultaneously measures the
      electrochemical current from the reduction of TNT and the conductance change of
      the polymer nanojunction caused from the reduction product. The hybrid detection
      mechanism, together with the unique selective preconcentration capability of the
      ionic liquid, provides a selective, fast, and sensitive detection of TNT. The
      sensor, in its current form, is capable of detecting parts-per-trillion level TNT
      in the presence of various interferents within a few minutes.

PMID- 20041700
TI  - On-chip single plasmon detection.
AB  - Surface plasmon polaritons (plasmons) have the potential to interface electronic
      and optical devices. They could prove extremely useful for integrated quantum
      information processing. Here we demonstrate on-chip electrical detection of
      single plasmons propagating along gold waveguides. The plasmons are excited using
      the single-photon emission of an optically emitting quantum dot. After
      propagating for several micrometers, the plasmons are coupled to a
      superconducting detector in the near-field. Correlation measurements prove that
      single plasmons are being detected.

PMID- 20041701
TI  - Significance of hydrophilic characters of organic dyes in visible-light hydrogen
      generation based on TiO2.
AB  - A series of dyes were synthesized to examine the roles of the hydrophilic
      characteristics of R in sensitized hydrogen generation by dye-grafted Pt/TiO(2)
      under visible light irradiation. The hydrogen-generation efficiencies and optimum
      amounts of the dyes grafted to Pt/TiO(2) were affected substantially by the
      hydrophilic and steric effects of R; moderately hydrophilic DEO1 and DEO2 showed
      higher sensitization activity at a lower loading than hydrophobic D-H.

PMID- 20041702
TI  - O-acetyl oximes as transformable directing groups for Pd-catalyzed C-H bond
      functionalization.
AB  - O-Acetyl oximes serve as effective directing groups for Pd-catalyzed sp(2) and
      sp(3) C-H functionalization reactions. The C-H functionalization products can be
      subsequently transformed into ortho- or beta-functionalized ketones, alcohols,
      amines, and heterocycles.

PMID- 20041703
TI  - Synthesis, fungicidal activity, and structure-activity relationship of spiro
      compounds containing macrolactam (macrolactone) and thiadiazoline rings.
AB  - Two series of novel spiro-compounds containing macrolactam or macrolactone and
      thiadiazoline rings, 1-thia-2-alkylimino-3,4,9-triaza-10-oxospiro[4.15]eicosyl-3
      ene (4F) and 1-thia-2-alkylimino-3,4-diaza-9-oxa-10-oxospiro[4.15]eicosyl-3-ene
      (4G), were synthesized from 12-oxo-1,15-pentadecanlactam and 12-oxo-1,15
      pentadecanlactone, respectively. Their structures were confirmed by elemental
      analysis, (1)H NMR, and (13)C NMR. The conformation of compounds 4F was
      determined via the crystal structure of a representative compound (4F(6)). The
      bioassay showed that compounds 4F have much better fungicidal activity against
      five fungi ( Botrytis cinerea Pers., Sclerotinia sclerotiorum , Rhizoctonia
      solani Kuhn., Phomopsis asparagi Sacc., and Pyricularia oryzae Cav.) than
      compounds 4G. The fact above showed that the presence of a hydrogen-bonding donor
      for the fungicidal activity of macrocyclic compounds is very important. 4F(6)
      showed excellent fungicidal activity against P. oryzae, which is much better than
      the commercial fungicide isoprothiolane, and 4F(13) showed excellent fungicidal
      activity against P. oryzae and good fungicidal activity against P. asparagi.

PMID- 20041704
TI  - Melodinines A-G, monoterpenoid indole alkaloids from Melodinus henryi.
AB  - Nineteen monoterpenoid indole alkaloids including seven new ones, melodinines A-G
      (1-7), were isolated from Melodinus henryi. The structures of the new compounds
      were elucidated using spectroscopic methods, and the structure of compound 4 was
      confirmed by single-crystal X-ray diffraction analysis. The known compounds were
      identified by comparing their spectroscopic data with those reported in the
      literature. All of the compounds were evaluated for cytotoxic activity against
      five human cancer cell lines, and compound 11 exhibited cytotoxicity against HL
      60, SMMC-7721, A-549, and SK-BR-3 cells with IC50 values of 2.0, 16.8, 25.9, and
      24.7 microM, respectively.

PMID- 20041705
TI  - Periodic trends in organic functionalization of group IV semiconductor surfaces.
AB  - Organic functionalization of group IV semiconductor surfaces provides a means to
      precisely control the interfacial properties of some of the most technologically
      important electronic materials in use today. The 2 x 1 reconstructed group IV
      (100) surfaces in ultrahigh vacuum, in particular, have a well-defined surface
      that allows adsorbate-surface interactions to be studied in detail. Surface
      dimers containing a strong sigma- and weak pi-bond form upon reconstruction of
      the group IV (100) surfaces, imparting a rich surface reactivity, which allows
      useful analogies to be made between reactions at the surface and those in classic
      organic chemistry. To date, most studies have focused on single substrates and a
      limited number of adsorbate functional groups. In this Account, we bring together
      experimental and theoretical results from several studies to investigate broader
      trends in thermodynamics and kinetics of organic molecules reacted with group IV
      (100)-2 x 1 surfaces. By rationalizing these trends in terms of simple periodic
      properties, we aim to provide guidelines by which to understand the chemical
      origin of the observed trends and predict how related molecules or
      functionalities will react. Results of experimental and theoretical studies are
      used to show that relative electronegativities and orbital overlap correlate well
      with surface-adsorbate covalent bond strength, while orbital overlap together
      with donor electronegativity and acceptor electron affinity correlate with
      surface-adsorbate dative bond strength. Using such simple properties as
      predictive tools is limited, of course, but theoretical calculations fill in some
      of the gaps. The predictive power inherent in periodic trends may be put to use
      in designing molecules for applications where controlled attachment of organic
      molecules to semiconductor surfaces is needed. Organic functionalization may
      facilitate the semiconductor industry's transition from traditional silicon-based
      architectures to other materials, such as germanium, that offer better electrical
      properties. Potential applications also exist in other fields ranging from
      organic and molecular electronics, where control of interfacial properties may
      allow coupling of traditional semiconductor technology with such developing
      technologies, to biosensors and nanoscale lithography, where the functionality
      imparted to the surface may be used directly. Knowledge of thermodynamic and
      kinetic trends and the fundamental basis of these trends may enable effective
      development of new functionalization strategies for such applications.

PMID- 20041706
TI  - Toward the ultimate limit of phase change in Ge(2)Sb(2)Te(5).
AB  - The limit to which the phase change memory material Ge(2)Sb(2)Te(5) can be scaled
      toward the smallest possible memory cell is investigated using structural and
      optical methodologies. The encapsulation material surrounding the Ge(2)Sb(2)Te(5)
      has an increasingly dominant effect on the material's ability to change phase,
      and a profound increase in the crystallization temperature is observed when the
      Ge(2)Sb(2)Te(5) layer is less than 6 nm thick. We have found that the increased
      crystallization temperature originates from compressive stress exerted from the
      encapsulation material. By minimizing the stress, we have maintained the bulk
      crystallization temperature in Ge(2)Sb(2)Te(5) films just 2 nm thick.

PMID- 20041707
TI  - Stereoselective synthesis of 2-C-acetonyl-2-deoxy-D-galactosides using 1,2
      cyclopropaneacetylated sugar as novel glycosyl donor.
AB  - 1,2-Cyclopropaneacetylated sugar is an effective glycosyl donor, which reacted
      with various glycosyl acceptors including monosaccharides, amino acids and other
      alcohols in the presence of BF(3)*OEt(2) or TMSOTf. The glycosylation is
      stereoselective in favor of beta-anomeric products with BF(3)*OEt(2) as catalyst,
      whereas TMSOTf-catalyzed glycosylation prefers the alpha-anomeric products. 2-C
      Acetonyl-2-deoxy-D-galactosides were obtained in good yields.

PMID- 20041708
TI  - Quantitative profiling and identification of outer membrane proteins of beta
      lactam resistant strain of Acinetobacter baumannii.
AB  - In the recent past, Acinetobacter baumannii in hospitals has become increasingly
      resistant to a number of antibiotics including the latest carbapenems and this is
      of great concern. Here, for the first time, we report 2D-Differential In-Gel
      Electrophoresis (DIGE) analysis of outer membrane proteome of ATCC 19606 and
      carbapenem-resistant strain of A. baumannii. Using biological variance analysis
      (BVA), we identified 25 differentially expressed proteins with a fold difference
      >or=2; confidence >90% and statistical significance p <or= 0.05. By applying
      MALDI TOF/TOF and ESI MS/MS proteomic approach to carbapenem-resistant A.
      baumannii, we identified four porins whose expression was significantly
      downregulated and a large number of upregulated proteins with specific transport
      and enzymatic properties. All the following synergistically give advantage to the
      resistant A. baumannii for survival: (i) high expression of altered CarO isoforms
      with possible low influx efficiency, (ii) elevated levels of CsuA/B with high
      adhesive properties, (iii) overexpression of pivotal nutrient transporters, (iv)
      continued expression of the major OmpAb, and (v) induced production of proteins
      of hypothetical origin. This proteomic study provides a platform to understand
      the complex nature of beta-lactam resistance in A. baumannii.

PMID- 20041709
TI  - Quantitative site-specific (2)H NMR investigation of MTBE: potential for
      assessing contaminant sources and fate.
AB  - Site-specific isotopic values of methyl tertiary butyl ether (MTBE) were measured
      using quantitative site-specific (2)H nuclear magnetic resonance (NMR)
      spectroscopy for seven commercially available MTBE products. The delta(2)H values
      of the methoxy and tertiary butyl groups ranged from -103 per thousand to -171
      per thousand, and from -76 per thousand to -104 per thousand, reflecting their
      production from methanol and isobutene, respectively. Several MTBE products whose
      whole-compound delta(13)C and delta(2)H MTBE values were within error of each
      other, as measured by isotope ratio mass spectrometry (IRMS), had demonstrably
      different delta(2)H values for their methoxy and tertiary butyl groups measured
      by (2)H NMR. Site-specific isotopic variations were large enough to provide proof
      of principle that quantitative site-specific (2)H NMR may provide an additional
      parameter for contaminant sourcing at field sites. Isotopic variations were small
      enough to not bias the comparability of degradation-associated isotopic
      enrichment factors determined using different MTBE products. Calculated delta(2)H
      values for MTBE, derived as weighted averages of (2)H NMR measurements of the two
      functional groups, showed good agreement with IRMS measurements. The ability to
      gain accurate information about the site-specific isotopic ratios of (2)H/(1)H
      within a molecule offers considerable promise as a new environmental tool to
      track the source and fate of environmental contaminants.

PMID- 20041710
TI  - Highly efficient Cu(I)-catalyzed synthesis of N-heterocycles through a
      cyclization-triggered addition of alkynes.
AB  - An aminoalkyne (terminal or internal) and a terminal alkyne furnish
      functionalized five-, six-, and seven-membered N-heterocycles in excellent yields
      via a Cu(I)-catalyzed, one-pot, tandem hydroamination/alkynylation process.

PMID- 20041712
TI  - Tailored single-walled carbon nanotube--CdS nanoparticle hybrids for tunable
      optoelectronic devices.
AB  - The integration of organic and inorganic building blocks into novel nanohybrids
      is an important tool to exploit innovative materials with desirable
      functionalities. For this purpose, carbon nanotube--nanoparticle
      nanoarchitectures are intensively studied. We report here an efficient
      noncovalent chemical route to density-controllably and uniformly assemble single
      walled carbon nanotubes with CdS nanoparticles. The methodology not only promises
      the resulting hybrids will be solution-processable but also endows the hybrids
      with distinct optoelectronic properties including tunable photoresponse mediated
      by amine molecules. On the basis of these merits, reliable thin-film
      photoswitches and light-driven chemical sensors are demonstrated, which
      highlights the potential of tailored hybrids in the development of new tunable
      optoelectronic devices and sensors.

PMID- 20041711
TI  - Black Ge based on crystalline/amorphous core/shell nanoneedle arrays.
AB  - Direct growth of black Ge on low-temperature substrates, including plastics and
      rubber is reported. The material is based on highly dense, crystalline/amorphous
      core/shell Ge nanoneedle arrays with ultrasharp tips ( approximately 4 nm)
      enabled by the Ni catalyzed vapor-solid-solid growth process. Ge nanoneedle
      arrays exhibit remarkable optical properties. Specifically, minimal optical
      reflectance (<1%) is observed, even for high angles of incidence ( approximately
      75 degrees ) and for relatively short nanoneedle lengths ( approximately 1 mum).
      Furthermore, the material exhibits high optical absorption efficiency with an
      effective band gap of approximately 1 eV. The reported black Ge could potentially
      have important practical implications for efficient photovoltaic and
      photodetector applications on nonconventional substrates.

PMID- 20041713
TI  - Complex fluid analysis with the advanced distillation curve approach.
AB  - An improved method for measuring distillation curves reveals the physicochemical
      properties of complex fluids such as fuels.

PMID- 20041714
TI  - Synthesis, crystal structures, and luminescent properties of two series' of new
      lanthanide (III) amino-carboxylate-phosphonates.
AB  - Hydrothermal reactions of lanthanide(III) chlorides with 4-HOOC-C(6)H(4)
      CH(2)NHCH(2)PO(3)H(2) (H(3)L) at different ligand-to-metal (L/M) ratios afforded
      nine new lanthanide(III) carboxylate-phosphonates with two types of 3D network
      structures, namely, LnCl(HL)(H(2)O)(2) (Ln = Sm, 1; Eu, 2; Gd, 3; Tb, 4; Dy, 5;
      Er, 6) and [Ln(2)(HL)(H(2)L)(L)(H(2)O)(2)].4H(2)O (Ln = Nd, 7; Sm, 8; Eu, 9).
      Compounds 1-6 are isostructural and feature a 3D network in which the LnO(7)Cl
      polyhedra are interconnected by bridging CPO(3) tetrahedra into 2D inorganic
      layers parallel to the bc plane. These layers are further cross-linked by organic
      groups of the carboxylate-phosphonate ligands via the coordination of the
      carboxylate groups into a pillared-layered architecture. Compounds 7-9 are also
      isostructural and feature a 3D open-framework composed of 1D lanthanide(III)
      phosphonate inorganic slabs which are further bridged by organic groups of the
      carboxylate-phosphonate liagnds via the coordination of the carboxylate groups,
      forming large 1D tunnels along the b-axis which are filled by lattice water
      molecules. Luminescent measurements indicate that compounds 2, 4, and 5 show
      strong emission bands in red, green, and yellow light region, respectively.
      Magnetic properties of 2, 3, 5, and 7 have also been studied.

PMID- 20041715
TI  - Tailored synthetic polyamines for controlled biomimetic silica formation.
AB  - Organic compounds isolated from diatoms contain long-chain polyamines with a
      propylamine backbone and variable methylation levels and chain lengths. These
      long-chain polyamines are thought to be one of the important classes of molecules
      that are responsible for the formation of the hierarchically structured silica
      based cell walls of diatoms. Here we describe a synthetic route based on solid
      phase peptide synthesis from which well-defined long-chain polyamines with
      different chain lengths, methylation patterns, and subunits can be obtained.
      Quantitative silica precipitation experiments together with structural
      information about the precipitated silica structures gained by scanning and
      transmission electron microscopy revealed a distinct dependence of the amount,
      size, and form of the silica precipitates on the molecular structure of the
      polyamine. Moreover, the influence of the phosphate concentration was elucidated,
      revealing the importance of divalent anions for the precipitation procedure. We
      were able to derive further insights into the precipitation properties of long
      chain polyamines as functions of their hydrophobicity, protonation state, and
      phosphate concentration, which may pave the way for better control of the
      formation of nanostructured silica under ambient conditions.

PMID- 20041716
TI  - Synthesis and insecticidal evaluation of N-tert-butyl-N'-thio[1-(6-chloro-3
      pyridylmethyl)-2-nitroiminoimidazolidine]-N,N'-diacylhydrazines.
AB  - A series of novel N-tert-butyl-N'-thio[1-(6-chloro-3-pyridylmethyl)-2
      nitroiminoimidazolidine]-N,N'-diacylhydrazines were synthesized by the reaction
      of chlorosulfenyl(N-tert-butyl-N,N'-diacylhydrazines) with 1-(6-chloro-3
      pyridylmethyl)-2-nitroiminoimidazolidine (imidacloprid) in the presence of sodium
      hydride. Their larvicidal activities were evaluated. All of them exhibited
      insecticidal activities against Oriental armyworm and bean aphids. Toxicity
      assays indicated that at higher concentrations (200 mg L(-1)) the title compounds
      can kill aphids as fast as the parent imidacloprid in 2 h, whereas at lower
      concentration (10 mg L(-1)), the title compounds can induce a premature, abnormal
      and lethal larval moult after 3 days of treatment, like the parent
      diacylhydrazines.

PMID- 20041717
TI  - Characterization of sirtuin inhibitors in nematodes expressing a muscular
      dystrophy protein reveals muscle cell and behavioral protection by specific
      sirtinol analogues.
AB  - In oculopharyngeal muscular dystrophy (OPMD), a disease caused by polyalanine
      expansion in the nuclear protein PABPN1, the genetic inhibition of sirtuins and
      treatment with sirtuin inhibitors protect from mutant PABPN1 toxicity in
      transgenic nematodes. Here, we tested the SIRT1/2 inhibitors 1-12, bearing
      different degrees of inhibition, for protection against mutant PABPN1 toxicity in
      Caenorhabditis elegans. Compounds 2, 4, and 11 were the most efficient, revealing
      a potential therapeutic application for muscle cell protection in OPMD.

PMID- 20041719
TI  - Engineering double to quintuple stacks of a polarized aromatic in confined
      cavities.
AB  - Discrete, well-defined stacks of the polarized aromatic pyrene-4,5-dione (1) were
      assembled in the cavities of organic-pillared coordination cages (2). The number
      (n) of stacked guests depends on the pillar length, and up to quintuple stacks (n
      = 5) were observed when long (16.5 A) organic pillar ligands were incorporated.
      As previously reported, pyrene-4,5-dione (1) assembles into infinite columnar
      stacks in the solid state, but the present work demonstrates that the polarized 1
      has a strong propensity to stack in layers even in the absence of crystal packing
      effects. For n = 2 and 3 structures, crystallographic studies revealed that 1
      stacks by pi-pi interactions in the cavity in such a way that a net dipole moment
      is canceled. These results emphasize the important role of dipole-dipole
      interactions as well as pi-stacking interactions in the formation of columnar
      stacks of 1.

PMID- 20041718
TI  - Synthesis and anticonvulsant activities of (R)-N-(4'-substituted)benzyl 2
      acetamido-3-methoxypropionamides.
AB  - The structure-activity relationship (SAR) for the N-benzyl group in the clinical
      antiepileptic agent (R)-lacosamide [(R)-N-benzyl 2-acetamido-3
      methoxypropionamide, (R)-3] has been explored. Forty-three compounds were
      prepared and then evaluated at the National Institute of Neurological Disorders
      and Stroke Anticonvulsant Screening Program for seizure protection in the maximal
      electroshock (MES) and subcutaneous Metrazol models. Comparing activities for two
      series of substituted aryl regioisomers (2', 3', 4') showed that 4'-modified
      derivatives had the highest activity. Significantly, structural latitude existed
      at the 4'-site. The SAR indicated that nonbulky 4'-substituted (R)-3 derivatives
      exhibited superb activity, independent of their electronic properties. Activities
      in the MES test of several compounds were comparable with or exceeded that of (R)
      3 and surpassed the activities observed for the traditional antiepileptic agents
      phenytoin, phenobarbital, and valproate.

PMID- 20041720
TI  - Use of information visualization methods eliminating cross talk in multiple
      sensing units investigated for a light-addressable potentiometric sensor.
AB  - The integration of nanostructured films containing biomolecules and silicon-based
      technologies is a promising direction for reaching miniaturized biosensors that
      exhibit high sensitivity and selectivity. A challenge, however, is to avoid cross
      talk among sensing units in an array with multiple sensors located on a small
      area. In this letter, we describe an array of 16 sensing units of a light
      addressable potentiometric sensor (LAPS), which was made with layer-by-layer
      (LbL) films of a poly(amidomine) dendrimer (PAMAM) and single-walled carbon
      nanotubes (SWNTs), coated with a layer of the enzyme penicillinase. A visual
      inspection of the data from constant-current measurements with liquid samples
      containing distinct concentrations of penicillin, glucose, or a buffer indicated
      a possible cross talk between units that contained penicillinase and those that
      did not. With the use of multidimensional data projection techniques, normally
      employed in information visualization methods, we managed to distinguish the
      results from the modified LAPS, even in cases where the units were adjacent to
      each other. Furthermore, the plots generated with the interactive document map
      (IDMAP) projection technique enabled the distinction of the different
      concentrations of penicillin, from 5 mmol L(-1) down to 0.5 mmol L(-1). Data
      visualization also confirmed the enhanced performance of the sensing units
      containing carbon nanotubes, consistent with the analysis of results for LAPS
      sensors. The use of visual analytics, as with projection methods, may be
      essential to handle a large amount of data generated in multiple sensor arrays to
      achieve high performance in miniaturized systems.

PMID- 20041721
TI  - Estimation of migration-time and mobility distributions in organelle capillary
      electrophoresis with statistical-overlap theory.
AB  - The separation of organelles by capillary electrophoresis (CE) produces large
      numbers of narrow peaks, which commonly are assumed to originate from single
      particles. In this paper, we show this is not always true. Here, we use
      established methods to partition simulated and real organelle CEs into regions of
      constant peak density and then use statistical-overlap theory to calculate the
      number of peaks (single particles) in each region. The only required measurements
      are the number of observed peaks (maxima) and peak standard deviation in the
      regions and the durations of the regions. Theory is developed for the precision
      of the estimated peak number and the threshold saturation above which the
      calculation is not advisable due to fluctuation of peak numbers. Theory shows
      that the relative precision is good when the saturation lies between 0.2 and 1.0
      and is optimal when the saturation is slightly greater than 0.5. It also shows
      the threshold saturation depends on the peak standard deviation divided by the
      region's duration. The accuracy and precision of peak numbers estimated in
      different regions of organelle CEs are verified by computer simulations having
      both constant and nonuniform peak densities. The estimates are accurate to 6%.
      The estimated peak numbers in different regions are used to calculate migration
      time and electrophoretic-mobility distributions. These distributions are less
      biased by peak overlap than ones determined by counting maxima and provide more
      correct measures of the organelle properties. The procedure is applied to a
      mitochondrial CE, in which over 20% of peaks are hidden by peak overlap.

PMID- 20041723
TI  - Interaction of hydrophobically end-capped poly(ethylene glycol) with phospholipid
      vesicles: the hydrocarbon end-chain length dependence.
AB  - We have investigated the adsorption of hydrophobically end-capped poly(ethylene
      glycol) (HE-PEG) with carbon number (m) in the hydrocarbon end chain ranging from
      0 to 16 onto phospholipid membrane by use of quartz crystal microbalance with
      dissipation (QCM-D), surface plasmon resonance (SPR) and isothermal titration
      calorimetry (ITC). QCM-D and SPR studies show that the hydrophobic interaction
      between HE-PEG chains and the lipid membrane increases with the hydrocarbon chain
      length. At a low HE-PEG concentration, the adsorption cannot induce a vesicle-to
      bilayer transition until the carbon number is up to 16. However, at a high HE-PEG
      concentration, the adsorption results in a vesicle-to-bilayer transition at m >
      or = 12. ITC measurements demonstrate that enthalpy change (DeltaH) for the
      mixing of lipid vesicles with HE-PEG chains is too small to be detectable when m
      is less than 12. However, DeltaH changes from positive to negative as the carbon
      number increases from 12 to 16, indicating that the HE-PEG insertion increases
      with its hydrocarbon end-chain length. The present study reveals that the
      hydrophobic interaction between the lipid membrane and HE-PEG chains as well as
      the osmotic pressure drive the adsorption and insertion of such polymer chains.

PMID- 20041722
TI  - Characterization of scavengers of gamma-ketoaldehydes that do not inhibit
      prostaglandin biosynthesis.
AB  - Expression of cyclooxygenase-2 (COX-2) is associated with the development of many
      pathologic conditions. The product of COX-2, prostaglandin H(2) (PGH(2)), can
      spontaneously rearrange to form reactive gamma-ketoaldehydes called levuglandins
      (LGs). This gamma-ketoaldehyde structure confers a high degree of reactivity on
      the LGs, which rapidly form covalent adducts with primary amines of protein
      residues. Formation of LG adducts of proteins has been demonstrated in pathologic
      conditions (e.g., increased levels in the hippocampus in Alzheimer's disease) and
      during physiologic function (platelet activation). On the basis of knowledge that
      lipid modification of proteins is known to cause their translocation and to alter
      their function, we hypothesize that modification of proteins by LG could have
      functional consequences. Testing this hypothesis requires an experimental
      approach that discriminates between the effects of protein modification by LG and
      the effects of cyclooxygenase-derived prostanoids acting through their G-protein
      coupled receptors. To achieve this goal, we have synthesized and evaluated a
      series of scavengers that react with LG with a potency more than 2 orders of
      magnitude greater than that with the epsilon-amine of lysine. A subset of these
      scavengers are shown to block the formation of LG adducts of proteins in cells
      without inhibiting the catalytic activity of the cyclooxygenases. Ten of these
      selective scavengers did not produce cytotoxicity. These results demonstrate that
      small molecules can scavenge LGs in cells without interfering with the formation
      of prostaglandins. They also provide a working hypothesis for the development of
      pharmacologic agents that could be used in experimental animals in vivo to assess
      the pathophysiological contribution of levuglandins in diseases associated with
      cyclooxygenase up-regulation.

PMID- 20041724
TI  - Highly diastereoselective addition of alkynylmagnesium chlorides to N-tert
      butanesulfinyl aldimines: a practical and general access to chiral alpha-branched
      amines.
AB  - The addition of alkynylmagnesium chlorides to N-tert-butanesulfinyl imines
      proceeded with a remarkably high diastereoselectivity (dr > 13:1, mostly
      diastereopure), and with a general scope of both reaction partners. The high dr
      translated into simplified purification and higher optical purity for the
      synthesis of a wide array of chiral alpha-branched amines. The alkyne
      functionality also provides a multitude of opportunities for further synthetic
      transformations. The short asymmetric synthesis of (+)-angustureine 7 and (-)
      cuspareine 10 was realized with use of this approach.

PMID- 20041725
TI  - The effect of the preferential affinity of the solvent on the microstructure of
      solution-cast block copolymer thin films.
AB  - We have studied the microstructures of the solvent-cast films of polystyrene
      block-poly(methyl methacrylate) (PS-b-PMMA) diblock copolymer with PMMA cylinder
      forming composition. The casting solvents, 1,1,2-trichloroethane (TCE), toluene
      (Tol) and their binary mixtures, were controlled to evaporate at a certain rate R
      approximately 0.01 mL/h, and the effect of the preferential affinity of the
      solvents for a certain block P2VPng microstructures is investigated. 1,1,2
      Trichloroethane and toluene, with similar volatility, are good solvents for both
      PS and PMMA blocks but having opposite preferential affinity for each block (TCE
      has preferential affinity for the minority PMMA block and Tol has preferential
      affinity for the majority PS block), and the preferential affinity of the
      solvents is modulated by mixing the two solvents. As the preferential affinity of
      the solvents for the majority PS block increases, a series of microstructures
      including perforated lamella with ringlike morphologies, PMMA cylinders, PMMA
      spheres, and PMMA cylinders covered with a layer of PS microdomain have been
      observed. The results are discussed in view of the effective volume fraction of
      each block induced by the solvent preferential affinity and the special
      mechanical strain field brought by the solvent evaporation.

PMID- 20041726
TI  - Organogels from different self-assembling new dendritic peptides: morphology,
      rheology, and structural investigations.
AB  - Three new peptide based dendrimers with different generations were synthesized,
      purified, and characterized. Each of these dendrimers form efficient organogels
      under suitable conditions and these gels were characterized by field emission
      scanning electron microscopy (FE-SEM), high resolution transmission electron
      microscopy (HR-TEM), atomic force microscopy (AFM), Fourier transformed infrared
      (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and rheology. It
      has been observed that gel forming propensity increases from first to second
      generation dendrimer and it decreases from second to third generation. The
      hydrogen bonding interaction is the main driving force for the formation of
      aggregated structure that leads to the formation of a fibrillar network,
      responsible for gelation. The morphology is network type consisting of taped or
      twisted fibrils spanning throughout the space. DSC measurements show the
      thermoreversible first-order phase transition. Rheological studies indicate that
      flow behavior and segmental motion of these gels are different for different
      peptidic gels, obtained from various generations of dendritic peptides.

PMID- 20041727
TI  - Cooperative strengthening of an intramolecular O-H...O hydrogen bond by a weak C
      H...O counterpart: matrix-isolation infrared spectroscopy and quantum chemical
      studies on 3-methyl-1,2-cyclohexanedione.
AB  - Matrix-isolation infrared spectra of 1,2-cyclohexanedione (CD) and 3-methyl-1,2
      cyclohexanedione (3-MeCD) were measured in a nitrogen matrix at 8 K. The spectral
      features reveal that, in the matrix environment, both molecules exist exclusively
      in the monohydroxy tautomeric form, which is stabilized by an intramolecular O
      H...O=C hydrogen bond (HB). The nu(O-H) band of the enol tautomer of 3-MeCD
      appears at a relatively lower frequency and displays a somewhat broader bandwidth
      compared to that of CD, and these spectral differences between the two molecules
      are interpreted as being due to the formation of an interconnected C-H...O HB,
      where the enolic oxygen is the HB acceptor and one of the C-H covalent bonds of
      the methyl group is the HB donor. Electronic structure calculations at the
      B3LYP/6-311++G**, MP2/6-311++G**, and MP2/cc-pVTZ levels predict that this
      tautomer (enol-2) is approximately 3.5 kcal/mol more stable than a second enolic
      form (enol-1) where such interconnected H-bonding is absent. Theoretical analysis
      with a series of molecules having similar functional groups reveals that part of
      the excess stability (approximately 1 kcal/mol) of enol-2 originates from a
      cooperative interaction between the interconnected C-H...O and O-H...O HBs. In
      the IR spectrum, a weak band at 3007 cm(-1) is assigned to nu(C-H) of the methyl
      C-H bond involved in the H-bonded network. The spectra predicted by both harmonic
      and anharmonic calculations reveal that this transition is largely blue-shifted
      compared to the fundamentals of the other two methyl C-H stretching frequencies
      that are not involved in H-bonding. The conclusions are corroborated further by
      natural bond orbital (NBO) analysis.

PMID- 20041728
TI  - QM/MM study on the catalytic mechanism of cellulose hydrolysis catalyzed by
      cellulase Cel5A from Acidothermus cellulolyticus.
AB  - Cellulase Cel5A from Acidothermus cellulolyticus is an endoglucanase which
      features the retention mechanism for the cleavage of the beta-1,4-glycosidic
      bond. In this work, we investigated the detailed catalytic steps in the formation
      of two cellobiose units from the hydrolysis of a cellotetraose molecule using a
      combined QM/MM approach. The understanding of the catalysis process at the
      atomistic level may help further protein engineering research. Molecular
      dynamics, potentials of mean force (PMFs), and reaction path calculations
      confirmed that the hydrolysis of cellotetraose has a retention mechanism via
      oxocarbenium-like transition states for both the glycosylation and
      deglycosylation steps.

PMID- 20041733
TI  - The Einsteinian imperative.

PMID- 20041734
TI  - Measuring systemic inflammatory regulation in older adults: evidence and utility.
AB  - Aging is frequently accompanied by a proinflammatory state with adverse health
      consequences. This state is commonly assessed by markers in serum, either in
      isolation or ad hoc combination. We sought, alternatively, to develop scores
      summarizing multiple markers in accordance with biology on inflammatory
      regulation and evaluate their value added for discriminating functional outcomes
      in older adults. Data came from InCHIANTI (Invecchiare in Chianti; Aging in the
      Chianti Area) study participants age 65 years and older. Serum concentrations of
      seven inflammatory biomediators were subjected to latent variable analysis
      implementing a biological model of counterbalancing up- and down-regulation
      processes. Resulting process constructs were approximated by principal component
      scores; these, and individual markers, were evaluated as predictors of mobility
      impairment and frailty status in regression analyses, adjusting for key
      confounders. The biomediators' interrelationships were well predicted by the
      hypothesized biology. The up-regulation score was independently associated with
      worsened mobility functioning and frailty risk. For mobility, the association was
      stronger than, persisted independently of, and accounted for association with
      each biomediator. The down regulation score was associated with frailty outcomes.
      We conclude that systemic inflammation is relevant to the process that leads to
      functional loss in older persons and can be validly measured through biologically
      informed summary of inflammatory markers.

PMID- 20041735
TI  - Medical bioremediation: a concept moving toward reality.
AB  - Abstract A major driver of aging is catabolic insufficiency, the inability of our
      bodies to break down certain substances that accumulate slowly throughout the
      life span. Even though substance buildup is harmless while we are young, by old
      age the accumulations can reach a toxic threshold and cause disease. This
      includes some of the most prevalent diseases in old age-atherosclerosis and
      macular degeneration. Atherosclerosis is associated with the buildup of
      cholesterol and its oxidized derivatives (particularly 7-ketocholesterol) in the
      artery wall. Age-related macular degeneration is associated with carotenoid
      lipofuscin, primarily the pyridinium bisretinoid A2E. Medical bioremediation is
      the concept of reversing the substance accumulations by using enzymes from
      foreign species to break down the substances into forms that relieve the disease
      related effect. We report on an enzyme discovery project to survey the
      availability of microorganisms and enzymes with these abilities. We found that
      such microorganisms and enzymes exist. We identified numerous bacteria having the
      ability to transform cholesterol and 7-ketocholesterol. Most of these species
      initiate the breakdown by same reaction mechanism as cholesterol oxidase, and we
      have used this enzyme directly to reduce the toxicity of 7-ketocholesterol, the
      major toxic oxysterol, to cultured human cells. We also discovered that soil
      fungi, plants, and some bacteria possess peroxidase and carotenoid cleavage
      oxygenase enzymes that effectively destroy with varied degrees of efficiency and
      selectivity the carotenoid lipofuscin found in macular degeneration.

PMID- 20041736
TI  - Forty percent methionine restriction decreases mitochondrial oxygen radical
      production and leak at complex I during forward electron flow and lowers
      oxidative damage to proteins and mitochondrial DNA in rat kidney and brain
      mitochondria.
AB  - Eighty percent dietary methionine restriction (MetR) in rodents (without calorie
      restriction), like dietary restriction (DR), increases maximum longevity and
      strongly decreases mitochondrial reactive oxygen species (ROS) production and
      oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty
      acid unsaturation in rat liver. Mitochondrial ROS generation and the degree of
      fatty acid unsaturation are the only two known factors linking oxidative stress
      with longevity in vertebrates. However, it is unknown whether 40% MetR, the
      relevant methionine restriction degree to clarify the mechanisms of action of
      standard (40%) DR can reproduce these effects in mitochondria from vital tissues
      of strong relevance for aging. Here we study the effect of 40% MetR on ROS
      production and oxidative stress in rat brain and kidney mitochondria. Male Wistar
      rats were fed during 7 weeks semipurified diets differing only in their
      methionine content: control or 40% MetR diets. It was found that 40% MetR
      decreases mitochondrial ROS production and percent free radical leak (by 62-71%)
      at complex I during forward (but not during reverse) electron flow in both brain
      and kidney mitochondria, increases the oxidative phosphorylation capacity of
      brain mitochondria, lowers oxidative damage to kidney mitochondrial DNA, and
      decreases specific markers of mitochondrial protein oxidation, lipoxidation, and
      glycoxidation in both tissues. Forty percent MetR also decreased the amount of
      respiratory complexes I, III, and IV and apoptosis-inducing factor (AIF) in brain
      mitochondria and complex IV in kidney mitochondria, without changing the degree
      of mitochondrial membrane fatty acid unsaturation. Forty percent MetR, differing
      from 80% MetR, did not inhibit the increase in rat body weight. These changes are
      very similar to the ones previously found during dietary and protein restriction
      in rats. We conclude that methionine is the only dietary factor responsible for
      the decrease in mitochondrial ROS production and oxidative stress, and likely for
      part of the longevity extension effect, occurring in DR.

PMID- 20041737
TI  - Senescing cells share common features with dedifferentiating cells.
AB  - Dedifferentiation signifies the capacity of somatic cells to acquire stem cell
      like properties. This process can be induced during normal development and as a
      response to various stimuli, such as pathogen infection and wounding.
      Dedifferentiation also characterizes the transition of differentiated leaf cells
      into protoplasts (plant cells devoid of cell walls), a transition accompanied by
      widespread chromatin decondensation. Transcriptome profiling of dedifferentiating
      protoplast cells revealed striking similarities with senescing cells; both
      display a large increase in the expression of genes of specific transcription
      factor (TF) families, including ANAC, WRKY, bZIP, and C2H2. Further analysis
      showed that leaves induced to senesce by exposure to dark display characteristic
      features of dedifferentiating cells, including chromatin decondensation,
      disruption of the nucleolus, and condensation of rRNA genes. Considering that
      premature senescence can be induced by various stress conditions both in plant
      and animal cells, our results suggest that the response of plant and also animal
      cells to certain stresses converges on cellular dedifferentiation whereby cells
      first acquire stem cell-like state prior to acquisition of a new cell fate (e.g.,
      reentry into the cell cycle or death).

PMID- 20041739
TI  - Regenerative medicine through a crisis: social perception and the financial
      reality.
AB  - The aim of this perspective piece is to highlight how the "social perception" and
      "financial reality" of regenerative medicine may act to hinder its evolution into
      the principal health-care option for the future. We also consider the role of the
      consumer and the need for increased public awareness. Furthermore, we consider
      the effects of the changing social attitudes toward the field, as well as taking
      into account the influence of current and future political thinking. From a
      financial viewpoint, we analyze the compatibility of the current venture capital
      model with regenerative medicine start-ups and explore approaches to ensure
      sufficient funding and support throughout all stages of product development, for
      example, the modularization of funding.

PMID- 20041741
TI  - Life extension from a Christian point of view.

PMID- 20041738
TI  - Consuming a diet supplemented with resveratrol reduced infection-related
      neuroinflammation and deficits in working memory in aged mice.
AB  - Aged mice treated peripherally with lipopolysaccharide (LPS) show an exaggerated
      neuroinflammatory response and cognitive deficits compared to adults.
      Considerable evidence suggests resveratrol, a polyphenol found in red grapes, has
      potent antiinflammatory effects in the periphery, but its effects on the central
      inflammatory response and cognitive behavior are unknown. Therefore, the current
      study investigated if resveratrol dietary supplementation would inhibit
      neuroinflammation as well as behavioral and cognitive deficits in aged mice given
      LPS to mimic a peripheral infection. In initial studies, adult (3-6 months) and
      aged (22-24 months) mice were provided control or resveratrol-supplemented diet
      for 4 weeks and then injected intraperitoneally (i.p.) with saline or LPS, and
      locomotor activity and spatial working memory were assessed. As anticipated,
      deficits in locomotor activity and spatial working memory indicated aged mice are
      more sensitive to LPS compared to adults. More importantly, the LPS-induced
      deficits in aged animals were mitigated by dietary supplementation of
      resveratrol. In addition, resveratrol consumption reduced LPS-induced interleukin
      1beta (IL-1beta) in plasma and the IL-1beta mRNA in the hippocampus of aged mice.
      Finally, pretreatment of BV-2 microglial cells with resveratrol potently
      inhibited LPS-induced IL-1beta production. These data show that aged mice are
      more sensitive than adult mice to both the inflammatory and cognitive effects of
      peripheral immune stimulation and suggest that resveratrol may be useful for
      attenuating acute cognitive disorders in elderly individuals with an infection.

PMID- 20041742
TI  - Validated supercentenarian cases aged 114 and above.

PMID- 20041743
TI  - Personal profile: interview with James Joseph, Ph.D. Interview by Vicki Glaser.

PMID- 20041745
TI  - Molecular analysis of the microbial communities of Mars analog lakes in Western
      Australia.
AB  - Unique, shallow interdune lakes and groundwaters with extremely low pH and high
      salinity exist in Australia, along with nearby lakes that possess higher pH
      values. These acidic hypersaline environments are possibly the best modern
      terrestrial analogues for past martian environments. However, no previous
      microbiological analyses of these lakes have been conducted. During the
      Australian winter of 2005, water samples were taken from several hypersaline
      lakes located in southern Western Australia that possessed acidic to slightly
      alkaline pH. These samples were subjected to molecular analysis to identify
      bacterial communities. DNA extraction and polymerase chain reaction (PCR)
      amplification of the 16S rRNA gene sequences, by using universal bacterial
      primers, were also performed on the samples. Extracted DNA was amplified with
      1070 forward and 1392 GC-clamped reverse primers and analyzed by using denaturant
      gradient gel electrophoresis (DGGE). In addition, libraries were developed from
      DNA retrieved from four lakes, including a marginal marine neutral lake, an
      inland neutral lake, and two inland acid lakes, and selected clones with distinct
      operational taxonomic units were sequenced. The DGGE profiles and clone sequence
      data indicate that there are distinct, abundant, and diverse microbial
      populations in these Australian hypersaline environments, especially the acidic
      ones. These results are significant for two reasons: (1) they provide the first
      microbiological survey of natural acid saline lakes and (2) they hint at the
      possibility that there could have been a diverse microbial population in acidic
      hypersaline environments on Mars.

PMID- 20041746
TI  - Silica chimneys formed by low-temperature brine spring discharge.
AB  - Vertical pipes comprised of loose silica and lined by chert nodules have been
      observed in the abandoned Mafeking Quarry in central Manitoba, Canada. Discovery
      of microfossils within these features of the same age as the carbonate host rock
      indicates that they are a dissolution/replacement structure rather than infill of
      karst features by younger sediments. These features occur on the low thermal
      maturity edge of the intercratonic Williston Basin, are not associated with any
      known tectonic or hydrothermal activity, and show no sign of localized discharge
      of high-temperature fluids. Modern low-temperature brine springs with silica
      filled discharge channels occur nearby, which suggests the silica chimneys are
      relic spring channels. Geochemical models have shown that dissolution/replacement
      reactions would be expected due to mixing of brine spring water with shallow
      groundwater in the region. Results indicate that silica pipe features in the rock
      record cannot be assumed to be indicative of hydrothermal activity. At the same
      time, results increase the astrobiological significance of low-temperature
      siliceous deposits.

PMID- 20041747
TI  - The fate of amino acids during simulated meteoritic impact.
AB  - Delivery of prebiotic molecules, such as amino acids and peptides, in
      meteoritic/micrometeoritic materials to early Earth during the first 500 million
      years is considered to be one of the main processes by which the building blocks
      of life arrived on Earth. In this context, we present a study in which the
      effects of impact shock on amino acids and a peptide in artificial meteorites
      composed of saponite clay were investigated. The samples were subjected to
      pressures ranging from 12-28.9 GPa, which simulated impact velocities of 2.4-5.8
      km/s for typical silicate-silicate impacts on Earth. Volatilization was
      determined by weight loss measurement, and the amino acid and peptide response
      was analyzed by gas chromatography-mass spectrometry. For all compounds,
      degradation increased with peak pressure. At the highest shock pressures, amino
      acids with an alkyl side chain were more resistant than those with functional
      side chains. The peptide cleaved into its two primary amino acids. Some chiral
      amino acids experienced partial racemization during the course of the experiment.
      Our data indicate that impact shock may act as a selective filter to the delivery
      of extraterrestrial amino acids via carbonaceous chondrites.

PMID- 20041748
TI  - Laser-Induced Fluorescence Emission (L.I.F.E.): searching for Mars organics with
      a UV-enhanced PanCam.
AB  - The European Space Agency will launch the ExoMars mission in 2016 with a primary
      goal of surveying the martian subsurface for evidence of organic material. We
      have recently investigated the utility of including either a 365 nm light
      emitting diode or a 375 nm laser light source in the ExoMars rover panoramic
      camera (PanCam). Such a modification would make it feasible to monitor rover
      drill cuttings optically for the fluorescence signatures of aromatic organic
      molecules and map the distribution of polycyclic aromatic hydrocarbons (PAHs) as
      a function of depth to the 2 m limit of the ExoMars drill. The technique
      described requires no sample preparation, does not consume irreplaceable
      resources, and would allow mission control to prioritize deployment of organic
      detection experiments that require sample destruction, expenditure of non
      replaceable consumables, or both. We report here for the first time laser-induced
      fluorescence emission (L.I.F.E.) imaging detection limits for anthracene, pyrene,
      and perylene targets doped onto a Mars analog granular peridotite with a 375 nm
      Nichia laser diode in optically uncorrected wide-angle mode. Data were collected
      via the Beagle 2 PanCam backup filter wheel fitted with original blue (440 nm),
      green (530 nm), and red (670 nm) filters. All three PAH species can be detected
      with the PanCam green (530 nm) filter. Detection limits in the green band for
      signal-to-noise ratios (S/N) > 10 are 49 parts per million (ppm) for anthracene,
      145 ppm for pyrene, and 20 ppm for perylene. The anthracene detection limit
      improves to 7 ppm with use of the PanCam blue filter. We discuss soil-dependent
      detection limit constraints; use of UV excitation with other rover cameras, which
      provides higher spatial resolution; and the advantages of focused and wide-angle
      laser modes. Finally, we discuss application of L.I.F.E. techniques at multiple
      wavelengths for exploration of Mars analog extreme environments on Earth,
      including Icelandic hydrothermally altered basalts and the ice-covered lakes and
      glaciers of Dronning Maud Land, Antarctica.

PMID- 20041749
TI  - Phyllosilicate emission from protoplanetary disks: is the indirect detection of
      extrasolar water possible?
AB  - Phyllosilicates are hydrous minerals formed by interaction between rock and
      liquid water, and are commonly found in meteorites that originate in the asteroid
      belt. Collisions between asteroids contribute to zodiacal dust, which therefore
      reasonably could include phyllosilicates. Collisions between planetesimals in
      protoplanetary disks may also produce dust that contains phyllosilicates. These
      minerals possess characteristic emission features in the mid-infrared and could
      be detectable in extrasolar protoplanetary disks. We have determined whether
      phyllosilicates in protoplanetary disks are detectable in the infrared, using
      instruments such as those on board the Spitzer Space Telescope and the
      Stratospheric Observatory for Infrared Astronomy (SOFIA). We calculated opacities
      for the phyllosilicates most common in meteorites and, using a two-layer
      radiative transfer model, computed the emission of radiation from a
      protoplanetary disk. We found that phyllosilicates present at the 3% level lead
      to observationally significant differences in disk spectra and should therefore
      be detectable with the use of infrared observations and spectral modeling.
      Detection of phyllosilicates in a protoplanetary disk would be diagnostic of
      liquid water in planetesimals in that disk and would demonstrate similarity to
      our own Solar System. We also discuss use of phyllosilicate emission to test the
      "water worlds" hypothesis, which proposes that liquid water in planetesimals
      should correlate with the inventory of short-lived radionuclides in planetary
      systems, especially (26)Al.

PMID- 20041750
TI  - Chemical evolution of amphiphiles: glycerol monoacyl derivatives stabilize
      plausible prebiotic membranes.
AB  - The self-assembly of simple amphiphiles like fatty acids into cell-like
      membranous structures suggests that such structures were available on prebiotic
      Earth to support the origin of cellular life. However, the composition of
      primitive membranes remains unclear because the physical properties of the
      aqueous environment in which they assembled are relatively unconstrained in terms
      of temperature, pH, and ionic concentrations. It seems likely that early
      membranes were composed of mixtures of various amphiphiles in an aqueous medium
      warmed by geothermal activity prevalent in the Archean era. To better understand
      the properties of mixed bilayers formed by binary mixtures of single-chain
      amphiphiles under these conditions, we conducted stability experiments, using
      membranes composed of various fatty acids having hydrocarbon chain length between
      8 and 18 carbons, in mixtures with their glycerol monoacyl amphiphile derivatives
      (GMAs). The parameters investigated were critical vesicle concentration (CVC),
      encapsulation, and temperature-dependent stability. We found that hydrocarbon
      chain length and the presence of GMAs were major factors related to membrane
      stability. As chain length increased, GMA additions decreased the CVC of the
      mixtures 4- to 9-fold. Encapsulation ability also increased significantly as a
      function of chain length, which reduced permeation of small marker molecules.
      However, long exposures to temperatures in excess of 60 degrees C resulted in a
      total release of encapsulated solutes and extensive mixing of the membrane
      components between vesicles. We conclude that GMAs can significantly increase the
      stability of mixed amphiphile membranes, but further studies are required to
      establish model membranes that are stable at elevated temperatures.

PMID- 20041751
TI  - Environmental controls on photosynthetic microbial mat distribution and
      morphogenesis on a 3.42 Ga clastic-starved platform.
AB  - Three morphotypes of microbial mats are preserved in rocks deposited in shallow
      water facies of the 3.42 Ga Buck Reef chert (BRC). Morphotype alpha consists of
      fine anastomosing and bifurcating carbonaceous laminations, which loosely drape
      underlying detrital grains or form silica-filled lenses. Morphotype beta consists
      of meshes of fine carbonaceous strands intergrown with detrital grains and dark
      laminations, which loosely drape coarse detrital grains. Morphotype gamma
      consists of fine, even carbonaceous laminations that tightly drape underlying
      detrital grains. Preservation of nearly uncompacted mat morphologies and detrital
      grains deposited during mat growth within a well-characterized sedimentary unit
      makes quantitative correlation between morphology and paleoenvironment possible.
      All mats are preserved in the shallowest-water interval of those rocks deposited
      below normal wave base and above storm wave base. This interval is bounded below
      by a transgressive lag formed during regional flooding and above by a small
      condensed section that marks a local relative sea-level maximum. Restriction of
      all mat morphotypes to the shallowest interval of the storm-active layer in the
      BRC ocean reinforces previous interpretations that these mats were constructed
      primarily by photosynthetic organisms. Morphotypes alpha and beta dominate the
      lower half of this interval and grew during deposition of relatively coarse
      detrital carbonaceous grains, while morphotype gamma dominates the upper half and
      grew during deposition of fine detrital carbonaceous grains. The observed mat
      distribution suggests that either light intensity or, more likely, small
      variations in ambient current energy acted as a first-order control on mat
      morphotype distribution. These results demonstrate significant environmental
      control on biological morphogenetic processes independent of influences from
      siliciclastic sedimentation.

PMID- 20041752
TI  - Formation of gas-phase glycine and cyanoacetylene via associative detachment
      reactions.
AB  - The recent discovery of molecular negative ions in the interstellar medium
      suggests that these species may be reactive intermediates in astrochemical
      processes. Our recent studies indicate that these anions, despite their high
      electron binding energies, are reactive with atomic reagents. In this work, we
      report that two species of interstellar interest, glycine (NH(2)CH(2)COOH) and
      cyanoacetylene (HC(3)N), can be readily formed by associative detachment of their
      corresponding deprotonated anions with hydrogen atoms. The reaction rate
      constants for glycine anion (NH(2)CH(2)CO(2)(-)) and cyanoacetylene anion (C(3)N(
      )) with H atom have been measured to be 2.0 +/- 0.5 x10(-10) cm(3) s(-1) and 5.4
      +/- 0.2 x 10(-10) cm(3) s(-1), respectively, where the error bars represent one
      standard deviation of the mean; the estimated total error is +/- 50%. A possible
      reaction mechanism for chemical conversion of species observed in the
      interstellar medium is also described.

PMID- 20041754
TI  - Late residual gamma-H2AX foci in murine skin are dose responsive and predict
      radiosensitivity in vivo.
AB  - Accurate biodosimetry is needed to estimate radiation doses received in vivo from
      accidental or unwarranted radiation exposures. We investigated the use of DNA
      repair foci (e.g. gamma-H2AX) at late times after irradiation in vivo as a
      biodosimeter of initial ionizing radiation dose. Two radiosensitive strains (SCID
      and BALB/c) and two radioresistant strains (C57BL/6 and C3H/HeJ) were used to
      quantify gamma-H2AX foci in a skin tissue microarray after doses of 1 to 10 Gy at
      early and late times after irradiation (1 and 7 days). Using a 3D quantitative
      immunofluorescence microscopy analysis, we observed a dose response for gamma
      H2AX foci for all strains at 30 min, 24 h and 7 days after irradiation. The
      numbers of residual foci were significantly different between each of the four
      strains and reflected the relative radiosensitivity in vivo. In comparing gamma
      H2AX focus and micronucleus formation after irradiation, we also observed
      association between the number of micronuclei and number of foci after 1 and 7
      days between radiosensitive and radioresistant strains. We conclude that 3D image
      analysis of gamma-H2AX in skin can be used to detect relative radiosensitivity
      based on late residual gamma-H2AX foci. This technique may be a useful
      biodosimeter to determine dose at times up to 1 week after accidental or
      catastrophic radiation exposure in vivo.

PMID- 20041755
TI  - Revisiting strain-related differences in radiation sensitivity of the mouse lung:
      recognizing and avoiding the confounding effects of pleural effusions.
AB  - The mouse has been used extensively to model radiation injury to the lung, a
      major dose-limiting organ for radiotherapy. Substantial differences in the timing
      and sensitivity of this tissue between mouse strains have been reported, with
      some strains, including C57BL/6, being designated as "fibrosis-prone". Pleural
      effusions have also been reported to be a prominent problem in many mouse
      strains, but it remains unclear how this affects the lung function and survival
      of the standard C57BL/6 mouse. The purpose of this investigation was to re
      evaluate this strain in comparison with C57L and CBA mice after whole-thorax
      irradiation at doses ranging from 10 to 15 Gy. Breathing rate measurements, micro
      computerized tomography, lung tissue weight, pleural fluid weight and
      histopathology showed that the most prominent features were an early phase of
      pneumonitis (C57L and CBA) followed by a late incidence of massive pleural
      effusions (CBA and C57BL/6). A remarkable difference was seen between the C57
      strains: The C57L mice were exquisitely sensitive to early pneumonitis at 3 to 4
      months while C57BL/6 mice showed a delayed response, with most mice presenting
      with large accumulations of pleural fluid at 6 to 9 months. These results
      therefore caution against the routine use of C57BL/6 mice in radiation lung
      experiments because pleural effusions are rarely observed in patients as a
      consequence of radiotherapy. Future experiments designed to investigate genetic
      determinants of radiation lung damage should focus on the high sensitivity of the
      C57L strain (in comparison with CBA or C3H mice) and the possibility that they
      are more susceptible to pulmonary fibrosis as well as pneumonitis.

PMID- 20041756
TI  - Hypoxia/reoxygenation-induced mutations in mammalian cells detected by the flow
      cytometry mutation assay and characterized by mutant spectrum.
AB  - Under hypoxic conditions, cells are more resistant to cell killing by ionizing
      radiation by a factor of 2.5 to 3, potentially compromising the efficacy of
      radiotherapy. It has been shown recently that hypoxic conditions alone are
      sufficient to generate mutations in vitro and in vivo, likely due to the creation
      of reactive oxygen species (ROS) and a decrease in mismatch and homologous
      recombination DNA repair activity. These factors are known precursors to the
      onset of genetic instability and poor prognosis. We have previously characterized
      the flow cytometry mutation assay and its sensitivity to detect significant
      mutant fractions induced by genotoxic agents that are not detected by other
      mammalian assays. Here we measure the mutant fraction induced by hypoxia. CHO
      A(L) cells cultured at <0.1% O(2) for 24 h generated a significant mutant
      fraction of 120 x 10(-5) and had growth kinetics and survival characteristics
      similar to those obtained with other mutagens. We investigated the role of ROS by
      treating cells with the radical scavenger DMSO, which significantly reduced
      hypoxia toxicity and mutagenesis. Single cells were sorted from the mutant
      population, and the resulting clonal populations were stained for five antigens
      encoded by genes found along chromosome 11 to generate mutant spectra. The
      mutations were primarily large deletions, similar to those in background mutants,
      but the frequency was higher. We have demonstrated that hypoxic conditions alone
      are sufficient to generate mutations in mammalian cells in culture and that the
      spectrum of mutations is similar to background mutations.

PMID- 20041757
TI  - Homologous recombination contributes to the repair of DNA double-strand breaks
      induced by high-energy iron ions.
AB  - To test the contribution of homologous recombinational repair (HRR) in repairing
      DNA damage sites induced by high-energy iron ions, we used (1) HRR-deficient
      rodent cells carrying a deletion in the RAD51D gene and (2) syngeneic human cells
      impaired for HRR by RAD51D or RAD51 knockdown using RNA interference. We found
      that in response to exposure to iron ions, HRR contributed to cell survival in
      rodent cells and that HRR deficiency abrogated RAD51 focus formation.
      Complementation of the HRR defect by human RAD51D rescues both enhanced
      cytotoxicity and RAD51 focus formation. For human cells irradiated with iron
      ions, cell survival was decreased, and in p53 mutant cells, the levels of
      mutagenesis were increased when HRR was impaired. Human cells synchronized in S
      phase exhibited a more pronounced resistance to iron ions compared with cells in
      G(1) phase, and this increase in radioresistance was diminished by RAD51
      knockdown. These results indicate a role for RAD51-mediated DNA repair (i.e. HRR)
      in removing a fraction of clustered lesions induced by charged-particle
      radiation. Our results are the first to directly show the requirement for an
      intact HRR pathway in human cells in ensuring DNA repair and cell survival after
      exposure to high-energy high-LET radiation.

PMID- 20041758
TI  - Cancer and non-cancer risks in normal and cancer-prone Trp53 heterozygous mice
      exposed to high-dose radiation.
AB  - This report tests the hypotheses that cancer proneness elevates risk from a high
      radiation exposure and that the risk response to high doses is qualitatively
      similar to that from low doses. Groups of about 170 female mice heterozygous for
      Trp53 (Trp53(+/-)) and their normal female littermates (Trp53(+/+)) were exposed
      at 7-8 weeks of age to (60)Co gamma-radiation doses of 0, 1, 2, 3 or 4 Gy at a
      high dose rate (0.5 Gy/min) or 4 Gy at a low dose rate (0.5 mGy/min). In the
      absence of radiation exposure, Trp53 heterozygosity reduced life span
      approximately equally for death from either cancer or non-cancer disease.
      Heterozygosity alone produced a 1.5-fold greater shortening of life span than a 4
      Gy acute exposure. Per unit dose, life shortening from cancer or non-cancer
      disease was the same for normal mice and Trp53 heterozygous animals, indicating
      that, contrary to previous reports, Trp53 heterozygosity did not confer radiation
      sensitivity to high doses of gamma rays. In Trp53(+/-) mice with cancer, life
      shortening from acute doses up to 4 Gy was related to both increased tumor
      formation and decreased tumor latency. A similar tumor response was observed in
      normal mice, but only up to 2 Gy, indicating that above 2 Gy, normal Trp53
      function protected against tumor initiation, and further life shortening
      reflected only decreased latency for cancer and non-cancer disease. Dose-rate
      reduction factors were 1.7-3.0 for both genotypes and all end points. We conclude
      that Trp53 gene function influences both cancer and non-cancer mortality in
      unexposed female mice and that Trp53-associated cancer proneness in vivo is not
      correlated with elevated radiation risk. Increased risk from high acute radiation
      doses contrasts with the decreased risk seen previously after low doses of
      radiation in both Trp53 normal and heterozygous female mice.

PMID- 20041760
TI  - G2-phase chromosomal radiosensitivity of primary fibroblasts from hereditary
      retinoblastoma family members and some apparently normal controls.
AB  - We previously described an enhanced sensitivity for cell killing and gamma-H2AX
      focus induction after both high-dose-rate and continuous low-dose-rate gamma
      irradiation in 14 primary fibroblast strains derived from hereditary-type
      retinoblastoma family members (both affected RB1(+/-) probands and unaffected
      RB1(+/+) parents). Here we present G(2)-phase chromosomal radiosensitivity assay
      data for primary fibroblasts derived from these RB family members and five
      Coriell cell bank controls (four apparently normal individuals and one bilateral
      RB patient). The RB family members and two normal Coriell strains had
      significantly higher ( approximately 1.5-fold, P < 0.05) chromatid-type
      aberration frequencies in the first postirradiation mitosis after doses of 50 cGy
      and 1 Gy of (137)Cs gamma radiation compared to the remaining Coriell strains.
      The induction of chromatid-type aberrations by high-dose-rate G(2)-phase gamma
      irradiation is significantly correlated to the proliferative ability of these
      cells exposed to continuous low-dose-rate gamma irradiation (reported in Wilson
      et al., Radiat. Res. 169, 483-494, 2008). Our results suggest that these
      moderately radiosensitive individuals may harbor hypomorphic genetic variants in
      genomic maintenance and/or DNA repair genes or may carry epigenetic changes
      involving genes that more broadly modulate such systems, including G(2)-phase
      specific DNA damage responses.

PMID- 20041761
TI  - Premature chromosome condensation (PCC) assay for dose assessment in mass
      casualty accidents.
AB  - The study was undertaken to establish a dose calibration curve for a practical
      PCC ring assay and to apply it in a simulated mass casualty accident. The PCC
      assay was validated against the conventional dicentric assay. A linear
      relationship was established for PCC rings after (60)Co gamma irradiation with
      doses up to 20 Gy. In the simulated accident experiment, 62 blood samples were
      analyzed with both the PCC ring assay and the conventional dicentric assay,
      applying a triage approach. Samples received various uniform and non-uniform (10
      40% partial-body) irradiations up to doses of 13 Gy. The results indicated that
      both assays yielded good dose estimates for the whole-body exposure scenario,
      although in the lower-dose range (0-6 Gy) dicentric scoring resulted in more
      accurate whole-body estimates, whereas PCC rings were better in the high-dose
      range (>6 Gy). Neither assay was successful in identifying partial-body
      exposures, most likely due to the low numbers of cells scored in the triage mode.
      In conclusion, the study confirmed that the PCC ring assay is suitable for use as
      a biodosimeter after whole-body exposure to high doses of radiation. However,
      there are limitations for its use in the triage of people exposed to high,
      partial-body doses.

PMID- 20041759
TI  - Effects of the AT1 receptor antagonist L-158,809 on microglia and neurogenesis
      after fractionated whole-brain irradiation.
AB  - Cognitive dysfunction develops in approximately 50% of patients who receive
      fractionated whole-brain irradiation and survive 6 months or more. The mechanisms
      underlying these deficits are unknown. A recent study demonstrated that treatment
      with the angiotensin II type 1 receptor antagonist (AT(1)RA) L-158,809 before,
      during and after fractionated whole-brain irradiation prevents or ameliorates
      radiation-induced cognitive deficits in adult rats. Given that (1) AT(1)RAs may
      function as anti-inflammatory drugs, (2) inflammation is thought to contribute to
      radiation injury, and (3) radiation-induced inflammation alters progenitor cell
      populations, we tested whether the cognitive benefits of L-158,809 treatment were
      associated with amelioration of the sustained neuroinflammation and changes in
      neurogenesis that are induced by fractionated whole-brain irradiation. In rats
      examined 28 and 54 weeks after irradiation, L-158,809 treatment did not alter the
      effects of radiation on the number and activation of microglia in the perirhinal
      cortex and hippocampus, nor did it prevent the radiation-induced decrease in
      proliferating cells and immature neurons in the hippocampus. These findings
      suggest that L-158,809 does not prevent or ameliorate radiation-induced cognitive
      deficits by modulation of chronic inflammatory mechanisms, but rather may reduce
      radiation-induced changes that occur earlier in the postirradiation period and
      that lead to cognitive dysfunction.

PMID- 20041762
TI  - The influence of radon exposures on lung cancer mortality in German uranium
      miners, 1946-2003.
AB  - Extensive uranium extraction took place from 1946 until 1990 at the former Wismut
      mining company in East Germany. A total of 58,987 male former employees of this
      company form the largest single uranium miners cohort that has been followed up
      for causes of mortality occurring from the beginning of 1946 to the end of 2003.
      The purpose of this study was to investigate and evaluate different forms of
      models for the radon exposure-related lung cancer mortality risk based on 3,016
      lung cancer deaths and 2 million person years. Other exposure covariables such as
      occupational exposure to external gamma radiation, long-lived radionuclides,
      arsenic, fine dust and silica dust are available. The standardized mortality
      ratio for lung cancer is 2.03 (95% CI: 1.96; 2.10). The simple cohort excess
      relative risk (ERR/WLM) for lung cancer is estimated as 0.0019 (95% CI: 0.0016;
      0.0022). The BEIR VI model produced risks similar to those obtained with a
      selected mathematically continuous ERR model for lung cancer. The continuous
      model is linear in radon exposure with exponential effect modifiers that depend
      on the whole range of age at median exposure, time since median exposure, and
      radon exposure rate. In this model the central estimate of ERR/WLM is 0.0054 (95%
      CI: 0.0040; 0.0068) for an age at median exposure of 30 years, a time since
      median exposure of 20 years, and a mean exposure rate of 3 WL. The ERR decreases
      by 5% for each unit of exposure-rate increase. The ERR decreases by 28% with each
      decade increase in age at median exposure and also decreases by 51% with each
      decade increase in time since median exposure. The method of determination of
      radon exposure (i.e., whether the exposures were estimated or measured) did not
      play an important role in the determination of the ERR. The other exposure
      covariables were found to have only minor confounding influences on the ERR/WLM
      for the finally selected continuous model when included in an additive way.

PMID- 20041763
TI  - Absence of short-term effects of UMTS exposure on the human auditory system.
AB  - The aim of this study, which was performed in the framework of the European
      project EMFnEAR, was to investigate the potential effects of Universal Mobile
      Telecommunications System (UMTS, also known as 3G) exposure at a high specific
      absorption rate (SAR) on the human auditory system. Participants were healthy
      young adults with no hearing or ear disorders. Auditory function was assessed
      immediately before and after exposure to radiofrequency (RF) radiation, and only
      the exposed ear was tested. Tests for the assessment of auditory function were
      hearing threshold level (HTL), distortion product otoacoustic emissions (DPOAE),
      contralateral suppression of transiently evoked otoacoustic emission (CAS effect
      on TEOAE), and auditory evoked potentials (AEP). The exposure consisted of speech
      at a typical conversational level delivered via an earphone to one ear, plus
      genuine or sham RF-radiation exposure obtained by an exposure system based on a
      patch antenna and controlled by software. Results from 73 participants did not
      show any consistent pattern of effects on the auditory system after a 20-min UMTS
      exposure at 1947 MHz at a maximum SAR over 1 g of 1.75 W/kg at a position
      equivalent to the cochlea. Analysis entailed a double-blind comparison of genuine
      and sham exposure. It is concluded that short-term UMTS exposure at this
      relatively high SAR does not cause measurable immediate effects on the human
      auditory system.

PMID- 20041764
TI  - Analysis of the contribution of charge transport in iodine-125-induced DNA
      damage.
AB  - Auger electron emitters like (125)I are the radionuclides of choice for gene
      targeted radiotherapy. The highly localized damage they induce in DNA is produced
      by three mechanisms: direct damage by the emitted Auger electrons, indirect
      damage by diffusible free radicals produced by Auger electrons traveling in
      water, and charge neutralization of the residual, highly positively charged
      tellurium daughter atom by stripping electrons from covalent bonds of neighboring
      residues. The purpose of our work was to determine whether these mechanisms
      proceed through an intermediate energy transfer step along DNA. It was proposed
      that this intermediate step proceeds through the charge transport mechanism in
      DNA. Conventional charge transport has been described as either a hopping
      mechanism initiated by charge injection into DNA and propagated by charge
      migration along the DNA or a tunneling mechanism in which charge moves directly
      from a donor to an acceptor within DNA. Well-known barriers for the hopping
      mechanism were used to probe the role of charge transport in (125)I-induced DNA
      damage. We studied their effect on the distribution of DNA breaks produced by the
      decay of (125)I in samples frozen at -80 degrees C. We found that these barriers
      had no measurable effect on the distribution of (125)I-induced breaks.

PMID- 20041765
TI  - Effect of quadruplex conformation on radiation-induced formation of 8
      hydroxyguanine and unaltered base release in polyguanylic acid.
AB  - The ability of guanine-rich sequences to form quadruplex structures in telomeres
      for example is important in a number of biological processes such as aging,
      carcinogenesis and gene regulation. Ionizing radiation can cause damage to
      guanine moieties that can affect the stability or formation of the guanine
      quadruplex structures. In addition, the mechanisms of formation of these
      radiation damages in quadruplex structures may be different from those that occur
      in single- or double-stranded conformations. We have studied the quantitative
      aspects of the radiation induced formation of 8-hydroxy-2'-guanine base
      modifications and unaltered guanine base release in single-, double- and four
      stranded conformations of polyriboguanylic acid as a model of guanine-rich
      sequences in telomere-like structures. The results show that the strandedness of
      guanine-rich sequences is an important variable in the observed yields of these
      base damages and suggests that telomere-like structures with G-quadruplexes will
      be relatively more radiosensitive than the other regions of duplex DNA. Hydroxyl
      radicals are the major reactive species that produce the DNA damage, although the
      presence of oxygen significantly reduces their radiation yields for all
      conformations of polyriboguanylic acid and changes the proportions of the yields
      of the various damages among the polymer conformations.

PMID- 20041766
TI  - CT guidance is needed to achieve reproducible positioning of the mouse head for
      repeat precision cranial irradiation.
AB  - To study the effects of cranial irradiation, we have constructed an all-plastic
      mouse bed equipped with an immobilizing head holder. The bed integrates with our
      in-house Small Animal Radiation Research Platform (SARRP) for precision focal
      irradiation experiments and cone-beam CT. We assessed the reproducibility of our
      head holder to determine the need for CT-based targeting in cranial irradiation
      studies. To measure the holder's reproducibility, a C57BL/6 mouse was positioned
      and CT-scanned nine times. Image sets were loaded into the Pinnacle(3) radiation
      treatment planning system and were registered to one another by one investigator
      using rigid body alignment of the cranial regions. Rotational and translational
      offsets were measured. The average vector shift between scans was 0.80 +/- 0.49
      mm. Such a shift is too large to selectively treat subregions of the mouse brain.
      In response, we use onboard imaging to guide cranial irradiation applications
      that require sub-millimeter precision.

PMID- 20041768
TI  - An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae
      Carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular
      characterization, epidemiology, and outcomes.
AB  - BACKGROUND: We describe the emergence and spread of Klebsiella pneumoniae
      carbapenemase 2 (KPC-2)-producing K. pneumoniae at a Greek University hospital.
      METHODS: Isolates with a carbapenem minimum inhibitory concentration >1 microg/mL
      and a negative EDTA-imipenem disk synergy test result were submitted to boronic
      acid disk test and to polymerase chain reaction (PCR) for KPC gene and
      sequencing. Records from patients who had KPC-2-producing K. pneumoniae isolated
      were retrospectively reviewed. Clinical isolates were submitted to molecular
      typing using pulsed-field gel electrophoresis, and the beta-lactamase content was
      studied using isoelectric focusing and PCR. RESULTS: From January 2007 through
      December 2008, 50 patients (34 in the intensive care unit [ICU]) were colonized
      (n = 32) or infected (n = 18) by KPC-2-producing K. pneumoniae. Increasing
      prevalence of KPC-2-producing K. pneumoniae coincided with decreasing prevalence
      of metallo-beta lactamase-producing isolates in our ICU. Multidrug resistance
      characterized the studied isolates, with colistin, gentamicin, and fosfomycin
      being the most active agents. Besides KPC-2, clinical isolates encoded TEM-1
      like, SHV-11, SHV-12, CTX-M-15, and LEN-19 enzymes. Four different clonal types
      were detected; the predominant one comprised 41 single patient isolates (82%).
      Sporadic multiclonal cases of KPC-2-producing K. pneumoniae infection were
      identified from September 2007 through May 2008. The outbreak strain was
      introduced in February 2008 and disseminated rapidly by cross-transmission; 38
      patients (76%) were identified after August 2008. Fourteen cases of bacteremia, 2
      surgical site infections, 2 lower respiratory tract infections (1 bacteremic),
      and 1 urinary tract infection were identified. Most patients received a colistin
      containing combination treatment. Crude mortality was 58.8% among ICU patients
      and 37.5% among non-ICU patients, but attributable mortality was 22.2% and 33.3%,
      respectively. CONCLUSIONS: The emergence of KPC-2-producing K. pneumoniae in
      Greek hospitals creates an important challenge for clinicians and hospital
      epidemiologists, because it is added to the already high burden of antimicrobial
      resistance.

PMID- 20041769
TI  - African traditional fermented foods and probiotics.
AB  - African traditional fermented foods remain the main source of nutrition for many
      rural communities in Africa. Although lactic acid bacteria are integral to many
      of these foods, little is known about the specific health benefits they confer or
      the properties of their strains. This mini-review explores the history of some
      African fermented foods and their microbial content and properties within the
      context of probiotic characteristics. Given the recent upsurge in probiotic
      research, recommendations are made on studies that could be performed with
      African fermented foods and their strains, with a view to improving the health of
      people in sub-Saharan Africa.

PMID- 20041770
TI  - Development of a database for government-funded health/functional food research.
AB  - The Korean Health/Functional Food Act of 2002 has led to the promotion of
      research on health/functional foods (HFFs). In order to track government-funded
      studies on HFFs, a free accessible database (National Research & Development on
      Functional Food, NaReaD(ff)) has been established by the Korea Food and Drug
      Administration. About 200 project reports funded by government agencies from 1993
      through 2007 were retrieved, using existing government-wide online databases
      created by the Korea Institute Science and Technology, Evaluation and Planning
      and the Korea Institute of Science and Technology Information. In 2008, the
      database was released with information regarding individual projects and
      technological achievements for individual ingredients with a vision for HFF
      development. Overall, government-funded HFF research has primarily involved
      botanicals including herbs and food plants. The immune system, oxidant stress
      alleviation, and the cardiovascular system are the three leading health systems
      being investigated. With regard to the types of studies performed, the majority
      were in vitro studies and animal studies with limited numbers of human
      intervention studies. Government funds have been fragmented for many different
      ingredients, and this represents a major gap in HFF development. This database is
      most valuable for evaluating trends in government-funded HFF research. It is also
      useful to identify research overlaps and gaps and to help research scientists
      within academia and industry identify potential sources of government funding.

PMID- 20041771
TI  - Proteomic analysis of the protective effects of Platycodi Radix in liver of
      chronically alcoholic rats.
AB  - In this study, we examined the effect of Platycodi Radix (PR) supplementation in
      chronically alcoholic rats. Sprague-Dawley rats were divided into three groups:
      control group (no alcohol), alcohol group (36.8% of total calories), and 0.3% PR
      group. The levels of serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) were increased by alcohol treatment, and PR
      supplementation normalized the AST level. Moreover, alcohol-induced cytochrome
      P450 2E1 was decreased by PR treatment. Proteomic analysis of liver tissues of
      alcohol-exposed rats and PR-supplemented rats revealed that 50 different proteins
      functionally characterized as involved with cytoskeleton regulation, signal
      transduction, cytokine, apoptosis, and reactive oxygen species metabolism showed
      significant quantitative changes. The expression levels of glutathione S
      transferase mu, Bcl-2-like protein, and peroxiredoxin IV were decreased in the
      alcoholic group, whereas the levels of these proteins were increased more than
      threefold in the PR group. However, the expression levels of smooth muscle actin,
      cytochrome P450 2D, mitogen-activated protein kinase 8, and 3alpha-hydroxysteroid
      dehydrogenase were increased in the alcohol group and were decreased in the PR
      group. These data suggest that the antioxidant enzymes may play a protective role
      against alcohol-induced damage via oxidative stress defense mechanisms induced by
      PR supplementation.

PMID- 20041772
TI  - Persimmon oligomeric proanthocyanidins extend life span of senescence-accelerated
      mice.
AB  - The anti-aging activities of persimmon oligomeric proanthocyanidins (POPs),
      reported to improve life span and behavioral characteristics associated with the
      aging process, were investigated using the senescence-accelerated mouse (SAM) P8,
      which is a good model for studies on aging-related behavioral changes as well as
      life span. We demonstrated that the administration of POPs extended the life span
      of SAMP8. In addition, POPs elevated Sirt1 expression, which is recognized as an
      essential factor for life span extension in the brain. On the other hand, the
      administration of POPs did not induce stereotypical behaviors such as rearing,
      jumping, and hanging from the lid of a cage, whereas food restriction increased
      these frequencies without a significant change in motor function. The present
      study suggests a promising role of POPs as anti-aging agents to extend life span,
      although further studies elucidating their anti-aging mechanisms acting are
      needed.

PMID- 20041773
TI  - Active principle of kimchi, 3-(4'-hydroxyl-3',5'-dimethoxyphenyl)propionic acid,
      retards fatty streak formation at aortic sinus of apolipoprotein E knockout mice.
AB  - We examined the beneficial effects of an active principle in kimchi, 3-(4'
      hydroxyl-3',5'-dimethoxyphenyl)propionic acid (HDMPPA), on atherogenesis in
      apolipoprotein E knockout (apoE KO) mice. ApoE KO mice were fed an atherogenic
      diet containing 1% cholesterol (control group) with an intraperitoneal injection
      of chemically synthesized HDMPPA (10 mg/kg/day) (HDMPPA group) for 8 weeks. The
      aortic sinus atherosclerotic lesion size in the HDMPPA group (n = 10) was
      significantly smaller (control vs. HDMPPA, 280,790 vs. 165,409 microm(2), P <
      .001). The level of reactive oxygen species (ROS) in the HDMPPA group was lower
      by 14%, compared with the control group (P < .05). Aortic NADPH oxidase activity
      was significantly lower in the HDMPPA group than in the control group. HDMPPA
      suppressed the mRNA expression of p47phox and rac-1 of NADPH oxidase by 27.2% and
      46.0%, respectively, compared with values of the control group. In conclusion,
      HDMPPA in kimchi may attenuate atherosclerosis in apoE KO mice through
      retardation of ROS generation via down-regulating the mRNA expression of p47phox
      and rac-1, which are the components of NADPH oxidase.

PMID- 20041774
TI  - Anti-inflammatory activities of extracts of Thai spices and herbs with
      lipopolysaccharide-activated RAW 264.7 murine macrophages.
AB  - Nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) play important
      roles in inflammatory processes. This study examined whether 13 spices/herbs
      commonly used in Thai dishes modulate the production of NO and TNF-alpha by the
      RAW 264.7 mouse macrophage cell line pretreated with plant extracts (1-100
      microg/mL) prior to activation by bacterial lipopolysaccharide (LPS). Tested
      plant tissues were extracted with ethanol with the exception of roselle, which
      was extracted with 70% acetone. Eight of the 13 plant extracts inhibited NO and
      TNF-alpha production in a dose-dependent manner without exerting cytotoxicity.
      Extract from Limnophila aromatica (Kyeng) was the most robust suppressor of NO
      production, followed by dill, kaffer lime, chili, Teaw, mint, sweet basil, and
      pea eggplant, respectively (range of 50% inhibitory concentration [IC(50)] = 11.4
      74.6 microg/mL). Kyeng also exhibited the greatest inhibition of TNF-alpha
      production (IC(50) = 10.5 microg/mL). IC(50) values for NO and TNF-alpha
      production in LPS-activated RAW 264.7 cells for these extracts were highly
      correlated (r = 0.772, P = .025). These results suggest that extracts from some
      spices/herbs in the habitual Thai diet possess anti-inflammatory activity.
      Moreover, the results support the use of NO production in LPS-activated RAW 264.7
      cells as a rapid and cost-effective tool for screening the anti-inflammatory
      activity of extracts of spices/herbs.

PMID- 20041775
TI  - Regulation of phase II enzymes by genistein and daidzein in male and female Swiss
      Webster mice.
AB  - The consumption of soy and soy isoflavones has been associated with a decreased
      risk of certain cancers. A factor contributing to this dietary chemoprevention is
      the activity of phase I and II biotransformation enzymes. This study evaluated
      the hypothesis that dietary soy isoflavones will increase hepatic and
      extrahepatic quinone reductase (QR), UDP-glucuronosyltransferase (UGT), and
      glutathione S-transferase (GST) phase II enzyme activities, under short-term
      feeding and basal (non-pharmacologic-induced) conditions. Male and female Swiss
      Webster mice were fed for 1, 3, 5, or 7 days of one of four treatments: control
      (casein AIN-93G) or control supplemented with flavone (positive control),
      genistein, or daidzein aglycones at 1,500 mg/kg of diet. QR activity was
      increased by daidzein in the liver, by both isoflavones in the kidney and small
      intestine, and by genistein in the heart. Genistein and daidzein slightly
      decreased UGT activities in some tissues. Liver GST activity was decreased by
      genistein in females. In contrast, genistein and daidzein increased kidney GST
      activity. In general, the greatest effects of isoflavones on phase II enzymes
      were observed in liver and kidney tissues, occurring at day 3, and peaking at day
      5. Sex effects in the liver and kidney included females exhibiting higher QR
      activities and males exhibiting higher UGT and GST activities. In conclusion,
      individual soy isoflavones modulate phase II enzymes in mice under short-term
      feeding and basal conditions. This study provides insights into the actions of
      isolated isoflavones in mice.

PMID- 20041776
TI  - Antilipogenic and hypolipidemic effects of ethanol extracts from two variants of
      Artemisia princeps Pampanini in obese diabetic mice.
AB  - The objective of this study was to determine the effects of the ethanol extract
      of two variants of Artemisia princeps Pampanini, Sajabalssuk (SB) and Sajuarissuk
      (SS), on lipid metabolism in type 2 diabetic animals. Male C57BL/KsJ-db/db mice
      were divided into control, SB ethanol extract (SBE) (0.171 g/100 g of diet), SS
      ethanol extract (SSE) (0.154 g/100 g of diet), and rosiglitazone (RG) (0.005
      g/100 g of diet) groups. Supplementation of SBE and SSE significantly lowered the
      plasma levels of free fatty acid, triglyceride, and total cholesterol compared to
      the control group. The hepatic triglyceride and cholesterol contents and hepatic
      lipid droplets accumulation were also significantly lower in the SBE- and SSE
      supplemented db/db mice than in the control or RG-supplemented db/db mice.
      Reductions of hepatic triglyceride and cholesterol contents in the SBE and SSE
      groups were related to the suppression of hepatic lipogenic enzyme activities,
      fatty acid synthesis (fatty acid synthase and malic enzyme), triglyceride
      synthesis (phosphatidate phosphohydrolase), and cholesterol synthesis (3-hydroxy
      3-methylglutaryl-coenzyme A reductase) and esterification (acyl-coenzyme
      A:cholesterol acyltransferase). The RG supplement lowered plasma and hepatic
      lipid levels compared to the control group. However, RG significantly increased
      the white and brown adipose tissue weight and epididymal adipocyte size, whereas
      SBE and SSE lowered the brown adipose tissue weight and epididymal adipocyte size
      compared to the RG group. Together, these data suggest that supplementation of
      SBE and SSE partly improves lipid dysregulation and fatty liver in db/db mice by
      suppressing hepatic lipogenic enzyme activities.

PMID- 20041777
TI  - Bioactive properties of wood knot extracts on cultured human cells.
AB  - Not all felled wood is converted to timber or pulp, with the remaining material
      being a rich source of relatively unexplored and unexploited potentially novel
      bioactive compounds. Therefore the potential bioactive effects of two softwood
      knot (the part of the branch encased in the tree stem) extracts--namely, Pinus
      banksiana Lamb. (Jack pine) and Picea sitchensis (Bong.) Carr. (Sitka spruce)-
      were investigated by (1) determining their effects on the viability and
      antioxidant status of human Jurkat T cells, (2) investigating potential
      cytoprotective and genoprotective effects against oxidative stress in cultured
      cells, and (3) assessing their effects on concanavalin A (ConA)-induced
      interleukin-2 (IL-2) production. Initially, both Jack pine knot and Sitka spruce
      knot extracts were shown to possess strong antioxidant activity as determined by
      the ferric reducing antioxidant power assay. When added to Jurkat cells, Jack
      pine knot extract was more toxic compared with Sitka spruce knot extract, with
      concentrations that resulted in 50% cell death of 153.0 microg/mL and 376.1
      microg/mL, respectively. Supplementation of Jurkat cells with wood knot extracts
      did not affect their glutathione content or catalase activity. Pretreatment of
      Jurkat cells with Sitka spruce or Jack pine knot extracts protected against
      H(2)O(2)-induced cell injury. However, none of the extracts protected against
      H(2)O(2)-induced DNA damage. Jack pine knots, at a concentration of 30 microg/mL,
      significantly suppressed ConA-induced IL-2 production. Although total phenol
      content did not differ between the two extracts, gas chromatography analysis did
      show variation in the types of constituents present. Further research is
      warranted to elucidate the selective bioactive properties of these softwood knot
      extracts.

PMID- 20041778
TI  - Red ginseng root extract mixed with Torilus fructus and Corni fructus improves
      facial wrinkles and increases type I procollagen synthesis in human skin: a
      randomized, double-blind, placebo-controlled study.
AB  - Red ginseng contains many bioactive constituents, including various ginsenosides
      that are believed to have antioxidant, immunostimulatory, and anti-aging
      activities. Yet, no controlled human study has explored its effects on photoaged
      skin. This study determined whether long-term intake of a red ginseng extract
      containing Torilus fructus and Corni fructus mixture reduces facial wrinkles and
      increases collagen synthesis in human skin. Healthy female volunteers over 40
      years of age were randomized in a double-blind fashion to receive either red
      ginseng extract-containing herbal mixture at 3 g/day or placebo for 24 weeks.
      Facial wrinkles, elasticity, epidermal water content, erythema, and pigmentation
      were measured objectively. Facial skin samples were taken before and after
      treatment, and real-time polymerase chain reaction and immunohistochemical
      analyses were undertaken for expression of type I procollagen, matrix
      metalloproteinase (MMP)-9, and fibrillin-1, which are wrinkle-related biochemical
      markers. A total of 82 subjects completed the study. Facial wrinkles were
      significantly improved, type I procollagen gene and protein expression was
      increased, MMP-9 gene induction was prevented, and fibrillin-1 fiber length was
      elongated only in the treatment group. No changes were seen in the facial
      elasticity, epidermal water content, facial erythema and pigmentation, and
      epidermal thickness in either group. Thus a red ginseng extract-containing
      Torilus fructus and Corni fructus mixture improves facial wrinkles, a clinical
      sign of photoaging, and this improvement is associated with biochemical and
      histological evidence of increased collagen synthesis in the dermis. These
      results substantiate the alleged beneficial effects of red ginseng on photoaging
      and support its use as an effective "beauty food."

PMID- 20041779
TI  - Effect of isoflavone-enriched milk on bone mass in ovariectomized rats.
AB  - This study examined the effect of isoflavone-enriched milk on bone loss in
      ovariectomized (OVX) rats. Thirty 6-week-old Sprague-Dawley female rats were
      divided into two groups: sham-operated and OVX. The OVX group was subdivided into
      three dietary groups (OVX, non-isoflavone-enriched milk; OVX+Iso, isoflavone
      enriched milk; and OVX+Iso+Vit+Ca, isoflavone-, vitamins D and K-, and Ca
      enriched mik). After 19 weeks of feeding, the food efficiency ratio and body
      weight gain in the sham-operated group were significantly lower compared with
      those in the other groups. The bone alkaline phosphatase and total alkaline
      phosphatase activities were significantly higher in isoflavone-enriched groups
      (OVX+Iso and OVX+Iso+Vit+Ca) when compared with the sham-operated group. Urinary
      excretions of deoxypyridinoline and hydroxyproline were significantly higher with
      ovariectomy, but mostly normalized in the OVX+Iso and OVX+Iso+Vit+Ca groups. The
      rats in the OVX+Iso and OVX+Iso+Vit+Ca groups showed higher femur and tibia
      weights. A significant increase was found in bone density of femur and trabecular
      bone area in the OVX+Iso+Vit+Ca group, which almost reached that of the sham
      operated group, whereas no difference was found among the OVX and OVX+Iso groups.
      The histological areas of the proximal tibia sections showed highly filled
      trabecular bone in both isoflavone-enriched groups (OVX+Iso and OVX+Iso+Vit+Ca).
      The present study indicated that isoflavone-enriched milk may have a partial
      preventive effect on ovariectomy-induced bone loss; however, vitamins D and K and
      Ca enrichment with isoflavone may enhance effectiveness for increasing bone mass
      in OVX rats.

PMID- 20041780
TI  - Carica papaya (Paw-Paw) unripe fruit may be beneficial in ulcer.
AB  - The anti-ulcer potentials of aqueous (AE) and methanol (ME) extracts of whole
      unripe Carica papaya fruit were evaluated using ethanol- and indomethacin-induced
      gastric ulcer models in rats. The effect of the extracts on small intestinal
      propulsion was also investigated. The extracts significantly reduced the ulcer
      index in both experimental models (P < .05) compared to the control group. ME
      showed a better protection against indomethacin-induced ulcers, whereas AE was
      more effective against ethanol-induced gastric ulcers. The extracts also
      significantly (P < .05) inhibited intestinal motility, with ME showing greater
      activity. Oral administration of AE and ME up to 5,000 mg/kg did not produce
      lethality or signs of acute toxicity in mice after 24 hours. The extracts of
      unripe C. papaya contain terpenoids, alkaloids, flavonoids, carbohydrates,
      glycosides, saponins, and steroids. The cytoprotective and antimotility
      properties of the extracts may account for the anti-ulcer property of the unripe
      fruit.

PMID- 20041782
TI  - Chemical composition and anti-stress effects of yeast hydrolysate.
AB  - In the present study, the anti-stress effects of yeast hydrolysate (YH) were
      investigated. The YH consisted of crude carbohydrate (23.6%) and crude protein
      (68.3%) with low contents of crude ash (3.1%) and crude fat (0.3%). Also, acidic
      amino acids (glutamic acid + aspartic acid) were present in large quantities
      (14.2 and 5.0 mol%, respectively). Pronase digestion had little effect on the
      affinity of the YH on 5-hydroxytryptamine (serotonin) and norepinephrine
      transporters, whereas NaIO(4) oxidation of the hydrolysate decreased the affinity
      by about 10% at 1,000 microg/mL, indicating that the periodate-labile
      carbohydrate moiety played a leading role in the affinity effects of the
      carbohydrate in YH. As a result of brain mapping after the administration of the
      YH for 3 days in human subjects, a symmetrical distribution of theta and alpha
      waves in the central and parietal lobes was observed. This brain mapping pattern
      of theta and alpha wave distribution appears in a psychologically stable state.
      The YH groups showed improvements in Beck Depression Inventory and Beck Anxiety
      Inventory scores after YH administration for 2 weeks. Treatment also seemed to
      have a more significant (P < .05) impact on the somatic manifestations of anxiety
      as indexed by the Beck Anxiety Inventory scores. Food materials used as a source
      of YH have been found to be associated with increases in alertness and adaptation
      to stress.

PMID- 20041781
TI  - Identification of Bacillus cereus in a chungkukjang that showed high anticancer
      effects against AGS human gastric adenocarcinoma cells.
AB  - Anticancer effects of chungkukjang (a Korean short-term fermented soy paste) were
      studied in human gastric adenocarcinoma cells, and Bacillus strains from
      chungkukjang were isolated and identified. Before the experiments, six different
      chungkukjang products (K-, M-, Mn-, O-, Os-, and H-chungkukjangs) were purchased
      from a folk village in the Sunchang region, Jeonbuk, Republic of Korea. Based on
      sensory evaluation tests and general chemical and quality studies, K-, H-, and M
      chungkukjangs were selected for the experiments. All chungkukjang samples
      exhibited in vitro anticancer activities; however, K-chungkukjang revealed the
      highest anticancer activity in the previous studies. In this experiment, K
      chungkukjang again showed the highest anticancer effect in the AGS cells. At the
      concentration of 1 mg/mL, K-chungkukjang (87%) showed the highest growth
      inhibitory effect, followed by H-chungkukjang (85%) and MC-chungkukjang (69%) (P
      < .05). K-chungkukjang induced apoptosis as determined by 4,6-diamidino-2
      phenylindole staining and exhibited increased bax and decreased bcl-2 mRNA
      expression. Three representative Bacillus strains from K-chungkukjang were
      isolated and identified by recA gene sequencing as Bacillus cereus, Bacillus
      amyloliquefaciens, and Bacillus subtilis. Identifying B. cereus in the
      chungkukjang means that when chungkukjang is prepared by the traditional method,
      B. cereus, which is a common cause of foodborne disease, can grow during the
      natural fermentation process. All B. cereus strains, of course, are not
      pathogens, but its presence causes food safety concerns. Therefore, using a
      starter culture is safer than the traditional natural fermentation for the
      industrialization of chungkukjang in Korea.

PMID- 20041783
TI  - Royal jelly (honey bee) is a potential antioxidant against cadmium-induced
      genotoxicity and oxidative stress in albino mice.
AB  - Cadmium (Cd) is a highly toxic heavy metal that induces genotoxic damage in the
      body. Besides, Cd induces oxidative damage in various tissues by altering
      antioxidant defence enzymes system. In this study, we investigated the protective
      role of royal jelly (RJ) on Cd-induced genotoxicity and oxidative stress in mice.
      For this aim, the micronucleus (MN) test in erythrocytes and exfoliated cells of
      buccal mucosa and the chromosome aberration (CA) test in bone marrow cells were
      applied. In addition, the levels of reduced glutathione (GSH) and malondialdehyde
      (MDA) were evaluated in the liver and kidneys. Thirty-six animals were divided
      into six groups: the control group received distilled water alone, whereas mice
      in the treatment groups received RJ alone (100 and 250 mg/kg of body weight), Cd
      alone (2 mg/kg of body weight), and RJ+Cd. Cd toxicity resulted in a significant
      (P < .05) increase in CAs, abnormal metaphase number, and MN formation. Cd also
      caused a decrease in mitotic index. Oral administration of RJ at two doses (100
      and 250 mg/kg of body weight) showed significant (P < .05) suppression of
      mutagenic effects of Cd. Moreover, Cd-induced oxidative damage caused a
      significant decrease in GSH level and a significant increase in MDA level in the
      liver and kidneys. Treatment with two doses of RJ caused a significant recovery
      in antioxidant status of GSH and a significant inhibition of MDA production. It
      could be concluded that RJ has a protective role against Cd-induced genotoxicity
      and oxidative stress in mice, due to its antioxidant effects.

PMID- 20041784
TI  - Protective effect of Codonopsis lanceolata root extract against alcoholic fatty
      liver in the rat.
AB  - Alcohol intake remains the most important cause of fatty liver throughout the
      world. The current study was undertaken to determine whether dietary
      supplementation with Codonopsis lanceolata root water extract attenuates the
      development of alcoholic fatty liver in rats and to elucidate the molecular
      mechanism for such an effect. Male Sprague-Dawley rats were fed normal diet (ND),
      ethanol diet (ED) (36% of total energy from ethanol), or 0.5% C. lanceolata root
      extract-supplemented ethanol diet (ED+C) for 8 weeks. C. lanceolata root water
      extract supplemented to rats with chronic alcohol consumption ameliorated the
      ethanol-induced accumulations of hepatic cholesterol and triglyceride. Chronic
      alcohol consumption up-regulated the hepatic expression of genes involved in
      inflammation, fatty acid synthesis, and cholesterol metabolism, including tumor
      necrosis factor alpha (TNFalpha), liver X receptor alpha (LXRalpha), sterol
      regulatory element-binding protein (SREBP)-1c, fatty acid synthase, acetyl
      coenzyme A carboxylase alpha (ACC), stearoyl-coenzyme A desaturase 1, 3-hydroxy-3
      methylglutaryl-coenzyme A reductase (HMGR), and low-density lipoprotein receptor
      (LDLR). The ethanol-induced up-regulations of TNFalpha, LXRalpha, SREBP-1c, HMGR,
      and LDLR genes in the liver were reversed by feeding C. lanceolata root water
      extract for 8 weeks. Moreover, ethanol-induced decreases in the ratio of phospho
      5'-AMP-activated protein kinase (AMPK) alpha/AMPKalpha and phospho-ACC/ACC
      protein levels in the liver were significantly restored (135% and 35% increases,
      respectively, P < .05) by supplementing them with C. lanceolata root water
      extract. In conclusion, C. lanceolata root water extract appears to be protective
      against alcoholic fatty liver through the regulation of SREBP-1c, LXRalpha, HMGR,
      and LDLR genes and by the phosphorylation of AMPKalpha and ACC, which are
      implicated in lipid metabolism.

PMID- 20041785
TI  - Antioxidant properties of raisins (Vitis vinifera L.).
AB  - Currants and sultanas (Vitis vinifera L., Family Vitaceae) are dried vine
      products produced in Greece and used widely in the Mediterranean diet. We
      investigated the polar methanol extracts from the raisins for the antiradical
      activity, polyphenol content, cytotoxicity in peripheral blood mononuclear cells,
      total glutathione (GSH) levels, oxidized glutathione (GSSG) levels, and
      inhibition of low-density lipoprotein (LDL) oxidation. Extracts exhibited 1,1
      diphenyl-2-picrylhydrazyl scavenging activity and inhibited tert
      butylhydroperoxide (tBHP)-induced cytotoxicity, GSH decrease, and LDL oxidation.
      Fluorescence microscopy revealed the characteristic apoptotic patterns with tBHP
      and inhibition with the extracts. Elevated levels of total GSH and unaltered
      levels of GSSG with extract treatment demonstrated the induction of gamma
      glutamylcysteine synthetase. The antioxidant activity was correlated to the
      polyphenolic content. Greek currants and sultanas are suggested as antioxidant
      components of the Mediterranean basin.

PMID- 20041786
TI  - Flavonoid-rich fraction from Sageretia theezans leaves scavenges reactive oxygen
      radical species and increases the resistance of low-density lipoprotein to
      oxidation.
AB  - To explore their bioactive fractions, Sageretia theezans leaves were extracted
      with 60% acetone and then fractionated sequentially with hexane, ethyl acetate,
      and water. Reactive oxygen radical species (ROS) (HOCl, ONOO(-), and O(2)(*-))
      scavenging activity, oxygen radical absorbance capacity (ORAC) value, and total
      phenolic content of each fraction were investigated. The ethyl acetate fraction
      had the largest total phenolic content and ORAC value and displayed the strongest
      ROS scavenging activity. The ethyl acetate fraction at 2 mumol of gallic acid
      equivalents/L prolonged the lag time of low-density lipoprotein oxidation by 260%
      compared to the control. In the ethyl acetate fraction, 7-O-methylmearnsetin 3-O
      rhamnoside and the other nine flavonols were characterized using high-performance
      liquid chromatography with electrochemical detection. The total flavonoid content
      in the ethyl acetate fraction was 460 mg/g. 7-O-Methylmyricetin 3-O-rhamnoside
      and 7-O-methylmearnsetin 3-O-rhamnoside were the predominant flavonoids, making
      up 36% and 17% of the total flavonoid content, respectively.

PMID- 20041787
TI  - Polyphenol composition and antioxidant potential of Hibiscus esculentus L. fruit
      cultivated in Nigeria.
AB  - Consumption of certain fruits and vegetables is now widely associated with
      chemoprevention of degenerative diseases like cancer and cardiovacsular disorders
      because of their antioxidant components. Polyphenols, a heterogeneous group of
      compounds, are one of these constituents. Hibiscus esculentus L. (Family
      Malvaceae), commonly referred to as okro, okra, or lady's finger, is an important
      component of diet in Nigeria and other countries in sub-Saharan Africa. In this
      article, we describe the polyphenol composition and antioxidant potential of H.
      esculentus of Nigerian origin. Quercetin glucoside (quercetrin) and an
      unidentified flavonoid were detected. In vitro antioxidant assay of methanol
      extract of the fruits showed potent antioxidant/radical scavenging activities
      with 50% inhibitory concentration values of 25 and 43 microL when analyzed by the
      xanthine oxidase and 2-deoxyguanosine methods, respectively. These data suggest
      that H. esculentus, popular especially during the rainy season in Nigeria and
      many tropical West, Central, and Eastern African countries, is a good contributor
      to the antioxidant status and disease chemoprevention of people in these
      countries.

PMID- 20041788
TI  - Evaluation of the polyphenol composition and antioxidant activity of African
      variety of Dacryodes edulis (G.Don) H.J Lam fruit.
AB  - Polyphenols are abundant micronutrients in our diet that have been credited with
      chemoprevention of diseases associated with oxidative stress. In this study, we
      investigated the whole ripened fruit of Dacryodes edulis (G.Don) H.J Lam, a
      multipurpose tree growing in West and Central Africa and other countries
      bordering the Gulf of Guinea, for polyphenol content as well as its
      antioxidant/radical scavenging capacity. Analysis of the methanol extract of the
      fruit by high-performance liquid chromatography coupled to an ultraviolet dual
      array detector and mass-selective detector revealed the presence of catechol
      (9.27 mg/kg), gallate (10.40 mg/kg), methylgallate (0.88 mg/kg), ellagic acid
      (3.10 mg/kg), quercetin (0.21 mg/kg), and quercetin rhamnoside (0.76 mg/kg). The
      extract showed very high antioxidant potential (50% inhibitory concentration
      [IC(50)] = 14 microL), but a rather weak radical scavenging activity (IC(50) =
      357 microL), when tested in vitro with the xanthine oxidase and 2-deoxyguanosine
      assay model systems, respectively. These results suggest that consumption of D.
      edulis could contribute to prevention of diseases that are related to oxidative
      stress.

PMID- 20041789
TI  - Protective effect of polyphenols from Glycyrrhiza glabra against oxidative stress
      in Caco-2 cells.
AB  - In the present article, we have investigated the antioxidant properties of
      methanolic liquorice polyphenol extracts (LPE(s)). Polyphenol extraction was
      performed with 60% and 100% methanol. Analysis of LPE(s) by thin-layer
      chromatography revealed that a higher amount of polyphenols was recovered by
      extraction with 60% methanol. Antioxidant activity measurement of the reducing
      power, scavenging effect on 2,2'-diphenyl-1-picrylhydrazyl free radical, and
      hydrogen peroxide scavenging capability have been taken as the parameters for
      assessment of antioxidant potential of LPE(s). Results have been compared with
      both natural and synthetic antioxidants. All experimental data have indicated
      that LPE(s) possess strong antioxidant power proportional to their o-diphenolic
      and total polyphenolic content, independently from the assay used. Therefore, the
      LPE(s) antioxidant property was examined against the cytotoxic effects of
      reactive oxygen species in human colon carcinoma cells. Pretreatment of Caco-2
      cells with liquorice polyphenolic extracts provided a remarkable protection
      against oxidative damage induced by H(2)O(2). The highest oxidative stress
      protection (72% of cell vitality) was measured in cells pretreated with 0.54 mM
      polyphenols. This effect seems to be associated to the antioxidant activity of
      liquorice polyphenolic compounds. Our data suggest that polyphenols from
      Glycyrrhiza glabra could exert a beneficial action in the prevention of
      intestinal pathologies related to production of reactive oxygen species.

PMID- 20041790
TI  - Effect of seasonal variations and collection form on antioxidant activity of
      propolis from San Juan, Argentina.
AB  - Propolis was included in the Argentine Food Code as a functional food. The
      chemical parameters and antioxidant properties of propolis samples from the same
      colonies of Apis mellifera in San Juan (Cuyo region, Western Argentine) were
      compared every month for 1 year using two collection methods. Chemical parameters
      were analyzed by the spectrophotometric method and fingerprinting using high
      performance liquid chromatography with ultraviolet detection. The antioxidant
      activities of propolis samples were measured using model systems including the
      analysis of the scavenging activities for 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and the
      beta-carotene bleaching assay. The results showed that propolis had a higher free
      radical scavenging and lipid peroxidation inhibitory capacity than butylated
      hydroxytoluene and quercetin, antioxidants used in the pharmaceutical and food
      industries. The concentration required to scavenge 50% of free radicals (SC(50))
      values differed depending on the sample collection month. Samples collected in
      November had the highest antioxidant capacity. In all cases, SC(50) values of
      propolis samples obtained by scraping were similar to those collected from a wire
      mesh (5 microg/mL for ABTS and 20-30 microg/mL for DPPH radicals). A significant
      positive correlation was found between the antioxidant capacity and flavonoid
      content of each analyzed extract. The chemical profiles were very similar.
      Galangin (3,5,7-trihydroxyflavone), an antioxidant compound, was detected in all
      samples as a major compound. The chromatographic profile suggests that of
      Baccharis sp., which would be one of the botanical sources of propolis from
      western Argentina, and the content of galangin can be used as a parameter for
      evaluating propolis quality. Our results suggest that Argentine propolis from
      Cuyo is a promising source of bioactive compounds as ingredients for developing
      functional foods with a beneficial impact on oxidative stress.

PMID- 20041791
TI  - Gamma-irradiation improves the color and antioxidant properties of Chaga mushroom
      (Inonotus obliquus) extract.
AB  - The objective of this study was to evaluate the effect of ionizing radiation on
      color and antioxidative properties of Chaga mushroom (Inonotus obliquus) extract
      (CME). CME (10 mg/mL) was gamma-irradiated at 0, 3, 5, 7, and 10 kGy, and color,
      antioxidant activity, and total phenolic compound levels were then determined.
      The lightness and yellowness were increased (P < .05), and the redness was
      decreased (P < .05), as irradiation dose increased. The antioxidant parameters
      such as the 2-diphenyl-1-picrylhydrazyl, superoxide, and hydroxyl radical
      scavenging activities, ferric reducing/antioxidant power, and inhibition of lipid
      peroxidation increased as the irradiation dose increased. Also, the total
      phenolic compound levels of CME were increased (P < .05) by gamma-irradiation.
      These results suggest that gamma-irradiation could be considered a means for
      improving the antioxidant properties and the color of CME.

PMID- 20041792
TI  - HemoHIM improves ovarian morphology and decreases expression of nerve growth
      factor in rats with steroid-induced polycystic ovaries.
AB  - Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the
      anovulation and cystic ovarian morphology. We investigated whether treatment with
      HemoHIM influences the ovarian morphology and the expression of nerve growth
      factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single
      intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling
      rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for
      35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every
      other day after EV injection. Ovarian morphology was almost normalized, and NGF
      was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of
      antral follicles and increased the number of corpora lutea in PCOs. The results
      are consistent with a beneficial effect of HemoHIM in the prevention and
      treatment of PCO syndrome.

PMID- 20041793
TI  - Protective effect of an herbal preparation (HemoHIM) on radiation-induced
      intestinal injury in mice.
AB  - The protective properties of an herbal preparation (HemoHIM) against intestinal
      damage were examined by evaluating its effects on jejunal crypt survival,
      morphological changes, and apoptosis in gamma-irradiated mice. The mice were
      whole-body irradiated with 12 Gy for the examination of jejunal crypt survival
      and any morphological changes and with 2 Gy for the detection of apoptosis and Ki
      67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment
      was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36
      and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a
      dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The
      HemoHIM-treated group displayed a significant increase in survival of jejunal
      crypts, when compared to the irradiation controls. HemoHIM treatment decreased
      intestinal morphological changes such as crypt depth, villus height, mucosal
      length, and basal lamina length of 10 enterocytes after irradiation. Furthermore,
      the administration of HemoHIM protected intestinal cells from irradiation-induced
      apoptosis. These results suggested that HemoHIM may be therapeutically useful to
      reduce intestinal injury following irradiation.

PMID- 20041794
TI  - Effects of a preparation of combined glutathione-enriched yeast and rice
      embryo/soybean extracts on ethanol hangover.
AB  - The effects of a preparation of combined glutathione-enriched yeast (GEY) and
      rice embryo/soybean (RES) extracts (20:1), GEY/RES, on experimentally induced
      ethanol hangover were investigated in male Sprague-Dawley rats. To evaluate the
      preventive effects on hangover, rats were orally administered GEY/RES (50/2.5,
      100/5, or 200/10 mg/kg) for 2 weeks. At 30 minutes after the final treatment,
      they were challenged with 3 mL/kg ethanol (15 mL of 20% in water/kg). The blood
      concentrations of alcohol and acetaldehyde were analyzed up to 7 hours
      postchallenge. Hepatic mRNA expression levels of alcohol-metabolizing enzymes,
      alcohol dehydrogenase (ADH), cytochrome P450 type 2E1 (CYP2E1), and aldehyde
      dehydrogenase (ALDH), were determined by real-time polymerase chain reaction.
      Additional rats were challenged with ethanol and, 60 minutes later, administered
      GEY/RES to evaluate alcohol clearance. Pretreatment with GEY/RES for 2 weeks
      reduced the blood concentrations of alcohol and acetaldehyde in a dose-dependent
      manner, lowering by 29.5% and 54.6% at the highest dose (200/10 mg/kg),
      respectively. The expressions of mRNAs for ADH and ALDH, the major alcohol
      metabolizing enzymes, were markedly increased in the livers of rats administered
      GEY/RES for 2 weeks, whereas CYP2E1 mRNA was suppressed. Postchallenge treatment
      with GEY/RES enhanced the alcohol clearance rate by lowering blood concentrations
      of alcohol and acetaldehyde by 24% and 26.6%, respectively, for the highest dose
      group. GEY/RES remarkably eliminated 2,2-diphenyl-1-picrylhydrazyl hydrate
      radical and FeCl(3)-mediated lipid peroxidation in vitro and attenuated hepatic
      lipid accumulation following ethanol administration in vivo. Therefore, it is
      suggested that GEY/RES reduces the blood concentrations of alcohol and
      acetaldehyde not only by modulating alcohol-metabolizing enzymes, but also by
      exerting its antioxidant activity, and that GEY/RES could be a promising
      candidate for improvements of alcoholic hangover.

PMID- 20041795
TI  - Zinc picolinate in the prevention of leiomyoma in Japanese quail.
AB  - Epidemiologic studies suggest that zinc deficiency may be associated with
      increased risk of cancer. We investigated the effects of zinc picolinate
      supplementation on the development of leiomyomas, malondialdehyde (MDA), 8
      isoprostane, 4-hydroxyalkenal (HAE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)
      levels, and heat shock protein 70 (Hsp70) expression in Japanese quails. One
      hundred fifty quails (6 months old) were assigned to three treatment groups
      consisting of 50 birds in each group. Birds were fed either a basal diet or the
      basal diet supplemented with 30 mg or 60 mg of zinc/kg of diet. The animals were
      sacrificed after 350 days, and the tumors were identified. Zinc picolinate
      supplementation did not affect the number of leiomyomas compared to control birds
      (P > .05). However, the tumors in zinc-fed birds were smaller than those found in
      control birds (P = .01) Serum MDA, 8-isoprostane, and HAE levels were lower in
      the treatment groups than in the control group: MDA, 1.95 versus 0.93 micromol/L;
      8-isoprostane, 108 versus 85 pg/mL; HAE, 1.55 versus 0.96 micromol/L (P = .01 for
      all three parameters). The concentrations of serum 8-OHdG, which is a marker of
      oxidative damage, in the groups were 28.5, 23.6, and 20.1 ng/mL, respectively (P
      = .01). Hsp70 expression was significantly decreased in zinc-treated birds (P <
      .01). The results indicate that dietary zinc picolinate supplementation reduces
      the growth of spontaneously occurring leiomyomas of the oviduct in the Japanese
      quail. Clinical trials should be conducted to investigate the efficacy of zinc
      supplementation in the prevention and treatment of uterine leiomyoma in humans.

PMID- 20041796
TI  - Vitamin A supplementation for different periods alters oxidative parameters in
      lungs of rats.
AB  - Lungs require an adequate supply of vitamin A (retinol) for normal embryonic
      development, postnatal maturation, and maintenance and repair during adult life.
      However, recent intervention studies revealed that supplementation with retinoids
      resulted in higher incidence of lung cancer, although the mechanisms underlying
      this effect are still unknown. Here, we studied the effect of vitamin A
      supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A
      supplementation at either therapeutic (1,000 and 2,500 IU/kg) or excessive (4,500
      and 9,000 IU/kg) doses for 3, 7, or 28 days induced lipid peroxidation, protein
      carbonylation, and oxidation of protein thiol groups, as well as change in
      catalase and superoxide dismutase activity. Together, these results suggest that
      vitamin A supplementation causes significant changes in redox balance, which are
      frequently associated with severe lung dysfunction.

PMID- 20041797
TI  - Antinociceptive effect of the extract of Morus nigra leaves in mice.
AB  - Morus nigra has been used to relieve pain in Brazilian folk medicine. This study
      was conducted to establish the antinociceptive properties of dichloromethane
      extract from leaves of M. nigra. The formalin, hot plate, and tail immersion
      tests as well as acetic acid-induced writhing were used to investigate the
      antinociceptive activity in mice. The extract at test doses of 100 and 300 mg/kg,
      p.o. clearly demonstrated antinociceptive activity in all tests. The extract
      administered at 300 mg/kg, p.o. had a stronger antinociceptive effect than
      indomethacin (5 mg/kg, p.o.) and morphine (10 mg/kg, p.o.), which supports
      previous claims for its traditional use.

PMID- 20041798
TI  - Influence of the target molecule on the oxygen radical absorbance capacity index:
      a comparison between alizarin red- and fluorescein-based methodologies.
AB  - A comparison of alizarin red (AR) and fluorescein (FL) as target molecules in
      oxygen radical absorbance capacity (ORAC)-like methods is reported. Galangin,
      apigenin, ferulic acid, and coumaric acid decreased AR initial consumption rate,
      whereas quercetin, kaempferol, luteolin, caffeic acid, and sinapic acid inhibited
      its consumption through an induction time, associated with a repair mechanism. On
      the other hand, all compounds protected FL with a clear induction time. AR was
      more selective and provides ORAC-AR values considerably smaller for compounds of
      low reactivity. The ORAC-AR value for luteolin was nearly 200 times that of
      coumaric acid. However, the ratio of ORAC-FL values for luteolin and coumaric
      acid was only 1.2. This different selectivity implies that AR provides ORAC
      values more related to reactivity than FL. ORAC-AR values of infusions were
      considerably smaller than the corresponding ORAC-FL values. These differences are
      interpreted in terms of the capacity of FL to generate induction times,
      irrespective of the reactivity of the additive. It is proposed that comparison of
      ORAC-AR and ORAC-FL values could afford a rough estimation of the average
      reactivity of the antioxidants titrated by the ORAC-FL methodology.

PMID- 20041799
TI  - Investigation of the effects of Aloe barbadensis on rat ovaries: a preliminary
      study.
AB  - Effects of Aloe barbadensis, a type of Aloe vera, on ovaries were investigated
      during pregnancy. A. vera gel, a commercial and nontherapeutic form of A.
      barbadensis, was used for this purpose. Three groups (one control and two test
      groups) of female Wistar albino rats with no prior births were studied. Group I
      was administered 25 mg (140 mg/kg) of A. barbadensis/day both orally and through
      gavage. A. barbadensis was contained in capsules with 500 mg of soybean oil;
      therefore Group II was administered 500 mg of soybean oil. Group III was the
      control group. All three groups were given normal food and water ad libitum. The
      substance had been administered for 20 days until birth. Ovaries were examined
      histologically. Vascular increase and the hyperemic form of ovary in the group
      administered A. barbadensis were notable. Decrease in primary follicle numbers,
      increase in secondary follicle numbers, and diminishment of secondary follicle
      diameters occurred in ovaries. The histological changes imply an angiogenesis
      effect of A. barbadensis and an effect like that of follicle-stimulating hormone
      in ovaries.

PMID- 20041800
TI  - Antibacterial and antifungal activities of some Mexican medicinal plants.
AB  - In Mexico about 4,000 plant species have some medicinal use. The aim of this work
      was to evaluate the antimicrobial activity of six Mexican medicinal plants
      against fungi and Gram-positive and Gram-negative bacteria. Methanolic extracts
      were prepared from the Mexican medicinal plants Amphypteringium adstrigens,
      Castella tortuosa, Coutarea latiflora, Ibervillea sonorae, Jatropha cuneata, and
      Selaginella lepidophylla. The antibacterial and antifungal activities of the
      plants were determined by the broth microdilution method and the radial growth
      inhibition assay, respectively. All Mexican plants tested showed antimicrobial
      activity. Among the six plant extracts analyzed, J. cuneata showed the highest
      growth-inhibitory activity against fungi, Gram-positive and Gram-negative
      bacteria (J. cuneata > A. adstrigens > C. latiflora > C. tortuosa > I. sonorae
      approximately S. lepidophylla). Shigella flexneri and Staphylococcus aureus were
      the most susceptible bacteria to plant extracts. Complete inhibition of S.
      flexneri growth was observed with J. cuneata methanolic extract at 90 microg/mL.
      This plant extract also showed the strongest antifungal activity against Fusarium
      verticillioides and Aspergillus niger. Our data suggest that the medicinal plants
      tested have important antimicrobial properties. This is the first report
      describing the antimicrobial activities of several of the Mexican medicinal
      plants used in this study.

PMID- 20041801
TI  - Bisabolol-induced gastroprotection against acute gastric lesions: role of
      prostaglandins, nitric oxide, and KATP+ channels.
AB  - The effects of Matricaria recutita and alpha-bisabolol, a bioactive component
      from Chamomile species, were investigated against gastric damage induced by
      absolute ethanol (96%, 1 mL per animal) in rats. The effects of M. recutita
      extract and alpha-bisabolol on gastric mucosal damage were assessed by
      determination of changes in mean gastric lesion area. Mechanistic studies were
      carried out at with 100 mg=kg alpha-bisabolol. We further examined the possible
      participation of prostaglandins, nitric oxide, and KATP+ channels in its
      mechanism. M. recutita reduced gastric damage in all doses tested. Alpha
      bisabolol at oral doses of 50 and 100 mg=kg markedly attenuated the gastric
      lesions induced by ethanol to the extent of 87% and 96%, respectively.
      Pretreatments with the nitric oxide antagonist N-nitro-l-arginine methyl ester
      (10 mg=kg, i.p.) or with indomethacin, an inhibitor of cyclooxygenase, failed to
      block effectively the gastroprotective effect of alpha-bisabolol. Furthermore,
      the alpha-bisabolol effect was significantly reduced in rats pretreated with
      glibenclamide, an inhibitor of KATP+ channel activation. Thus we provide evidence
      that alpha-bisabolol reduces the gastric damage induced by ethanol, at least in
      part, by the mechanism of activation of KATP+ channels.

PMID- 20041802
TI  - An examination of anthocyanins' and anthocyanidins' affinity for cannabinoid
      receptors.
AB  - A growing body of evidence suggests that anthocyanins and anthocyanidins may
      possess analgesic properties in addition to neuroprotective and anti-inflammatory
      activities. These functionalities suggest a role for the cannabinoid receptor
      (CB) in mediating biological effects. Competitive radioligand binding assays
      identified cyanidin (K(i) = 16.2 microM) and delphinidin (K(i) = 21.3 microM) as
      ligands with moderate affinity to human CB1. For CB2, similar affinities were
      achieved by cyanidin (K(i) = 33.5 microM), delphinidin (K(i) = 34.3 microM), and
      peonidin (K(i) = 46.4 microM). Inhibition constants >50 microM were obtained for
      pelargonidin, malvidin, cyanidin-3,5-di-O-glucoside, cyanidin-3-O-glucoside,
      cyanidin-3-O-galactoside, and cyanidin-3-O-rutinoside for both CB subtypes.

PMID- 20041803
TI  - Gastroprotective effect of Serjania erecta Radlk (Sapindaceae): involvement of
      sensory neurons, endogenous nonprotein sulfhydryls, and nitric oxide.
AB  - The present study reveals the pharmacological action of Serjania erecta Radlk.
      (Family Sapindaceae), an important medicinal plant species used in the Brazilian
      Pantanal against gastric pain. The methanolic (Me) and chloroformic (Se) extracts
      obtained from leaves of S. erecta were challenged by a very strong necrotizing
      agent in rodents, absolute ethanol. Se was also confronted with a nitric oxide
      synthase inhibitor (N(G)-nitro-L-arginine methyl ester), a capsaicin cation
      channel transient receptor potential vanilloid type 1 antagonist (ruthenium red),
      or a sulfhydryl-blocker (N-ethylmaleimide) to evaluate the participation of these
      cytoprotective factors in gastroprotection. In an in vivo experimental model, Me
      and Se presented several degrees of gastroprotective action without signs of
      acute toxicity. The best gastroprotective effect was restricted to all doses of
      Se. The mechanisms involving the gastroprotective action of Se are related to an
      augmented defense mechanism of the gastrointestinal mucosa consisting of sensory
      neurons, nitric oxide, and sulfhydryl groups that prevent and attenuate the ulcer
      process. The presence of polyisoprenoids in the Se explains the potent
      gastroprotective action of this medicinal species. Effective gastroprotective
      action and the absence of acute toxicity indicate this species may be a promising
      herbal drug against gastric disease.

PMID- 20041804
TI  - Percutaneous endoscopic gastrostomy in patients with systemic sclerosis.
AB  - Gastrointestinal (GI) problems are common in patients with systemic sclerosis
      (SSc) and some develop pronounced underweight despite dietary intervention. Two
      patients with SSc were referred to our department because of severe GI symptoms
      and critical underweight. They had lost 24 and 23 kg, respectively, and their
      body mass index (BMI) was only 15 and 17 kg/m(2), respectively. After careful GI
      evaluation, both were treated with percutaneous endoscopic gastrostomy (PEG).
      Eight months later one patient had gained 13 kg (BMI 19 kg/m(2)) and after 5
      months follow-up the other had gained 9 kg (BMI 20 kg/m(2)). Weight was no longer
      critically low and quality of life improved in both. In conclusion, PEG is an
      option in selected patients with severe malnutrition due to SSc. However, we
      advocate that thorough GI evaluation is performed in advance.

PMID- 20041805
TI  - Whole-body inhalation exposure to 1-bromopropane suppresses the IgM response to
      sheep red blood cells in female B6C3F1 mice and Fisher 344/N rats.
AB  - 1-Bromopropane (1-BP) is categorized as a high-production-volume chemical and is
      currently used in the manufacture of pharmaceuticals, pesticides, and other
      chemicals. Its usage is estimated to be around 5 million pounds per year,
      resulting in the potential for widespread exposure in the workplace. Case reports
      and animal studies have suggested exposure to this compound may cause adverse
      reproductive and neurological effects. Using a battery of immunological assays,
      the immunotoxicity of 1-BP after whole body inhalation exposure in both mice and
      rats was evaluated. Significant decreases in the spleen immunoglobulin (Ig) M
      response to sheep red blood cells (SRBC) were observed in both mice (125-500 ppm)
      and rats (1000 ppm) after exposure to 1-BP for 10 wk. In addition, total spleen
      cells and T cells were significantly decreased after approximately 4 wk of 1-BP
      exposure in both mice (125-500 ppm) and rats (1000 ppm). No change in natural
      killer (NK) cell activity was observed. The observed alterations in spleen
      cellularity, phenotypic subsets, and impairment of humoral immune function across
      species raise further concern about human exposure to 1-BP and demonstrate the
      need for additional investigations into potential adverse health effects.

PMID- 20041806
TI  - Public communication in unplanned biomass burning events.
AB  - Public communication related to emergency, unplanned, or "wildfire" biomass
      burning is best understood as a function of the audience for that communication.
      Two enduring communication models, the Health Belief Model and the Stages of
      Change or Transtheoretical Model, are instructive in analyzing and preparing
      differing communication response strategies that are indicated for communities
      with varying degrees of experience in responding to unplanned biomass burning
      smoke events.

PMID- 20041807
TI  - PCAF represses transactivation function of FOXO1 in an acetyltransferase
      independent manner.
AB  - The FOXO transcription factors play a key role in cell cycle control, apoptosis,
      DNA repair, oxidative stress resistance, and longevity. In this study, we
      demonstrated that the acetyltransferase p300/CBP associated factor (PCAF)
      functions as a negative regulator of FOXO1. We showed that PCAF bound to the
      forkhead domain of FOXO1 and acetylated FOXO1 at the K242 and K245 residues.
      However, PCAF repressed FOXO1-induced transcription in an enzymatic activity
      independent manner. In contrast, the transcriptional activity of FOXO1 S253A
      mutant, in which an Akt phosphorylation site is replaced by alanine, was not
      repressed by PCAF. Akt-induced phosphorylation of FOXO1 is required for its
      binding to PCAF, whereas the binding between FOXO1 and CBP is independent on
      FOXO1 S253 phosphorylation. Furthermore, overexpression of PCAF increased nuclear
      accumulation of FOXO1 even in the presence of serum. These results suggest that
      PCAF binds to phosphorylated FOXO1 by Akt and acts as a transcriptional
      corepressor in the nucleus.

PMID- 20041808
TI  - Biomass smoke exposures: toxicology and animal study design.
AB  - The International Biomass Smoke Health Effects (IBSHE) conference was convened in
      Missoula, MT, to define our current knowledge of smoke exposure and the potential
      health effects. In an effort to ascertain the relative health effects of an
      exposure to biomass smoke, numerous studies have utilized either animal or in
      vitro systems. A wide variety of systems that have been employed ranged from more
      mainstream animal models (i.e., rodents) and transformed cell lines to less
      common animal (piglets and dogs) and explant models. The Toxicology and Animal
      Study Design Workgroup at IBSHE was tasked with an analysis of the use of animal
      models in the assessment of the health effects of biomass smoke exposure. The
      present article contains a mini-review of models utilized historically, in
      addition to the adverse health effects assessed, and an overview of the
      discussion within the breakout session. The most common question that arose in
      discussions at the IBSHE conference was from local and federal health
      departments: What level of smoke is unhealthy? The present workgroup determined
      categories of exposure, common health concerns, and the availability of animal
      models to answer key health questions.

PMID- 20041809
TI  - Polyunsaturated fatty acids and human health: a critical appraisal of the
      evidence.

PMID- 20041810
TI  - The role of polyunsaturated fatty acids (PUFA) in the treatment of dyslipidemias.
AB  - Polyunsaturated fatty acids (PUFA) are a family of lipids including some
      subgroups identified by the position of the last double bond in their structure.
      PUFA n-3 include alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and
      docosahexaenoic acid (DHA), while PUFA n-6 include linoleic acid (LA) and
      arachidonic acid (AA). Since PUFA n-3 consumption has been shown to be inversely
      correlated with coronary heart diseases (CHD) incidence, clinical trials have
      been principally conducted by administering fish oil supplements or purified PUFA
      n-3. The relationship between dietary PUFA n-3 and CHD is believed to be only
      partially mediated by their effects on plasma lipoprotein profile. PUFA n-3 have
      shown to reduce only slightly total and LDL cholesterol, probably as they crowd
      saturated fatty acids out of diet. Data on HDL cholesterol suggest that PUFA n-3
      produce only a small increase in this fraction. The effect of PUFA n-3
      supplementation on plasma triglycerides (TG) is much more important, with a
      reduction of about 25% in normolipidemic subjects and about 50% in
      hypertriglyceridemic patients. This effect seems to be mediated by an inhibition
      of hormone-sensitive lipase, and VLDL secretion, and an increase in apo B liver
      degradation. They also increase lipoprotein lipase activity resulting in a
      reduction of post-prandial TG. PUFA n-3 might be used as second line therapy,
      additional or alternative to fibrates and nicotinic acid, in the treatment of
      severe hypertriglyceridemia. Furthermore, the addition of PUFA n-3 to statin
      therapy might contribute to normalize TG levels in patients with combined
      hyperlipidemia.

PMID- 20041811
TI  - Polyunsaturated fatty acids and cardiovascular disease.
AB  - Several observational and experimental studies show the beneficial effects of
      omega-3 poly-unsaturated fatty acids (PUFA) in cardiovascular disease. The
      results from such studies justify supplementation of omega-3 PUFA in primary and
      secondary prevention of several clinical conditions, including coronary heart
      disease, sudden cardiac death and heart failure. Supplementation of omega-3 PUFA
      is also indicated as monotherapy in the treatment of hypertriglyceridemia.
      Analysis of their biological actions suggests a variety of anti-arrhythmic, anti
      thrombotic, anti-atherosclerotic and anti-inflammatory mechanisms underlying
      their clinical benefits.

PMID- 20041812
TI  - Effects of dietary polyunsaturated fatty acids on mitochondria.
AB  - Type and quantity of ingested dietary fat contribute to the onset and progression
      of chronic diseases such as diabetes, obesity or arteriosclerosis. Attention is
      increasingly focussing on effective therapies for these diseases as well as
      functional foods that impede the development of insulin resistance and obesity.
      Studies provided evidence showing polyunsaturated fatty acids of the omega-3 and
      the omega-6 families play beneficial roles in prevention and treatment of
      diseases as diverse as Alzheimer's disease, cancer and cardiovascular diseases
      such as myocardial infarction, arrhythmia, atherosclerosis and hypertension.
      Strongest evidence is derived from in vitro experiments on cultured cells and
      animal-based studies, while the results from clinical studies are inconclusive.
      After ingestion, polyunsaturated fatty acids are distributed to cells and
      enriched in cellular membranes, where they influence cellular metabolism and
      survival. Polyunsaturated fatty acids are involved in various mitochondrial
      processes including mitochondrial calcium homeostasis, gene expression,
      respiratory function, ROS production and mitochondrial apoptosis. Therefore,
      mitochondria play a central role in the mechanisms underlying the protective
      effects of polyunsaturated fatty acids. The complex mechanisms involved in the
      effects of polyunsaturated fatty acid on mitochondrial actions depend on
      structural properties, cellular uptake, shuttling and metabolism, competition
      with intracellular stores as well as inherent properties of fatty acid
      metabolites. This review will summarize recent findings on the effects of various
      types of polyunsaturated fatty acids on mitochondria.

PMID- 20041813
TI  - Fatty acids and obesity.
AB  - Obesity is becoming a major public health problem worldwide. Its prevalence is
      increasing as well as the burden of diet-related chronic diseases including
      hypertension, diabetes, cardiovascular disease, stroke, and certain cancers. The
      link between obesity and chronic diseases is well established. Obese individuals
      are two to three times more likely to die prematurely than their lean
      counterparts, primarily due to the association between obesity and type 2
      diabetes and CHD. Over the past 20 years, there has been an increase in the
      scientific interest in the impact of omega-3 and omega- 6 fatty acids on human
      health. Several epidemiological and experimental studies have been published on
      the cardiovascular (CV) benefits of omega-3 fatty acids. Fish and fish oil are
      rich sources of omega- 3 fatty acids, specifically eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA). Alpha-linolenic acid (ALA) is an omega-3 fatty
      acid present in seeds and oils, green leafy vegetables, and nuts and beans.
      Linoleic acid (LA), an omega-6 fatty acid, is present in grains, meats, and the
      seeds of most plants. In addition, conjugated linoleic acid (CLA), a group of
      positional and geometric isomers of linoleic acid characterized by the presence
      of conjugated dienes, seems to confer specific cardiovascular benefits. The
      potential for unsaturated fatty acids to counteract the negative effects of
      obesity is substantial and deserves further investigation.

PMID- 20041814
TI  - PUFA supplements and type 2 diabetes in the elderly.
AB  - The prevalence of type 2 diabetes is increasing continuously, especially in older
      people. Such a rapidly rising risk has been linked to physical inactivity and
      evolutionary changes in dietary patterns (mainly characterized by a greater
      intake in dietary fat). Increased physical activity in any age group is
      associated with a lower risk of developing type 2 diabetes. Epidemiological
      studies also reported a lower incidence of type 2 diabetes in individuals who
      consumed n-3 polyunsaturated fatty acids (PUFA), while intake of total, saturated
      and/or monounsaturated fat was associated with increased risk of type 2 diabetes
      in glucose-intolerant individuals. Furthermore, the beneficial effects of PUFA
      consumption on cardiovascular disease were mainly attributed to their effects on
      reducing triglyceride levels, increasing high density lipoprotein cholesterol,
      and improving endothelial function through anti-inflammatory mechanisms and
      reduced platelet aggregation. In addition to common diabetic complications such
      as dyslipidemia and cardiovascular disease, elderly people with type 2 diabetes
      are at greater risk of specific geriatric syndromes, such as cognitive decline
      and physical disability. The threats of physical disability, loss of independence
      and loss of cognitive performance which diminish quality of life may ultimately
      be the greatest concern for those with type 2 diabetes. In this review we will
      address: i) specific dietary fat intake patterns and the development of insulin
      resistance and type 2 diabetes, ii) the effects of PUFA supplementation on
      glucose metabolism, diabetic dyslipidemia and cardiovascular disease, iii) the
      potential advantages of PUFA supplementation on cognitive decline and physical
      disability in the elderly.

PMID- 20041815
TI  - Omega-3 polyunsaturated fatty acids and immune-mediated diseases: inflammatory
      bowel disease and rheumatoid arthritis.
AB  - Inflammation is part of the normal host response to infection and injury.
      However, inappropriate inflammation contributes to several diseases, including
      inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Both conditions
      are characterized by the excessive production of inflammatory cytokines,
      arachidonic acid (AA)-derived eicosanoids, and other inflammatory agents (e.g.,
      reactive oxygen species, adhesion molecules). By virtue of their anti
      inflammatory action, omega-3 polyunsaturated fatty acids (PUFA) may be beneficial
      in inflammatory diseases. A large body of evidence supports a protective effect
      of omega-3 PUFA in experimental animal and ex-vivo models of Crohn's disease
      (CD), Ulcerative colitis (UC) and Rheumatoid arthritis (RA). Although fish oil
      supplementation in patients with IBD results in omega-3 PUFA incorporation into
      gut mucosal tissue and modification of inflammatory mediator profiles, the
      evidence of clinical benefits of omega-3 PUFA is weak. On the other hand, more
      convincing data support the efficacy of omega-3 PUFA in reducing pain, number of
      tender joints, duration of morning stiffness, use of non-steroidal anti
      inflammatory drugs and improving physical performance in RA patients. In both IBD
      and RA further clinical trials with large sample size are needed to clarify the
      efficacy of omega-3 PUFA as a treatment.

PMID- 20041817
TI  - The impact of omega-3 fatty acids on osteoporosis.
AB  - The essential polyunsaturated fatty acids (PUFAs) comprise 2 main classes: n-6
      and n-3 fatty acids. The most common source of n-6 fatty acids is linoleic acid
      (LA) which is found in high concentrations in various vegetable oils. Arachidonic
      acid (AA), the 20-carbon n-6 fatty acid, is obtained largely by synthesis from LA
      in the body. The n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic
      (DHA) are found in fish and fish oils. Long-Chain polyunsaturated fatty acids
      (LCPUFAs) and lipid mediators derived from LCPUFAs have critical roles in the
      regulation of a variety of biological processes including bone metabolism. There
      are different mechanisms by which dietary fatty acids affect bone: effect on
      calcium balance, effect on osteoblastogenesis and osteoblast activity, change of
      membrane function, decrease in inflammatory cytokines such as interleukin-1 (IL
      1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha), modulation
      of peroxisome proliferators-activated receptor gamma (PPARgamma). Animal studies
      have shown that a higher dietary omega-3/omega-6 fatty acids ratio is associated
      with beneficial effects on bone health. In spite of increasing evidence of the
      positive effects of dietary fats on bone metabolism from animal and in vitro
      studies, the few studies conducted in humans do not allow us to draw a definitive
      conclusion on their usefulness in clinical practice.

PMID- 20041816
TI  - Omega-3 and renal function in older adults.
AB  - Chronic kidney disease (CKD) is a major public health problem and can result in
      end-stage renal disease with need for dialysis or transplantation. In Europe up
      to 12% of the adult population had some renal impairment, while in the United
      States the end stage of CKD has increased dramatically from 209.000 in 1991 to
      472.000 in 2004. Diabetes and hypertension are major causes of kidney pathology.
      Infection, particularly ascending infection, is more common with increasing age,
      as both immune function declines and associated pathology predisposing to
      infection, such as obstructive uropathy, becomes more common. Most pathological
      changes in the kidney appear to be initiated by oxidative stress, followed by an
      inflammatory reaction. Oxidative stress results from an imbalance between free
      radicals and their detoxification by endogenous and exogenous scavengers,
      including polyunsaturated fatty acids (PUFA). Recent studies showed that PUFA
      supplementation slowed the rate of loss of renal function in patients with IgA
      nephropathy. Then, studies of omega-3 supplementation in dialysis patients
      describe salutary effects on triglyceride levels and dialysis access patency. We
      examined the relationship between total plasma PUFA levels and change in
      creatinine clearance over a three-year follow-up in the older persons enrolled in
      the InCHIANTI study, a population-based epidemiology study conducted in Tuscany,
      Italy. This study showed that older adults with low total plasma PUFA levels have
      a greater decline in creatinine clearance over three years of follow-up. These
      findings suggest that a higher dietary intake of PUFA may be protective against
      progression to chronic kidney disease.

PMID- 20041818
TI  - Omega-3 polyunsaturated fatty acids and depression: a review of the evidence.
AB  - Brain lipids contain a high proportion of polyunsaturated fatty acids (PUFA),
      which are a main component of cell membranes. Omega-3 (omega-3) PUFA
      eicosapentaeoic acid (EPA) and docosahexaenoic acid (DHA) are the most common
      PUFA in the brain. The physiological roles of omega-3 PUFA in the brain include
      regulation of cell membrane fluidity, dopaminergic and serotoninergic
      transmission, membrane-bound enzymes and cellular signal transduction. They are
      also thought to play a role in brain glucose metabolism, eicosanoid synthesis,
      gene expression, cell growth and protection from apoptosis. Increasing evidence
      from animal and human research shows omega-3 PUFA depletion may play an
      etiological role in several inflammatory, autoimmune and neuropsychiatric
      disorders. In particular, an association between omega-3 PUFA and depression was
      repeatedly suggested in observational and experimental studies on populations
      affected by major depression, depressed mood or post-partum depression.
      Consistently, the potential therapeutic role of omega-3 PUFA dietary
      supplementation was tested in clinical trials on depression. The current review
      identifies and evaluates available epidemiological evidence of a negative
      relationship between omega-3 PUFA and depression and examines its biological
      plausibility. Although current evidence increasingly supports an inverse
      association between omega-3 PUFA and depression, the validity of findings from
      observational and experimental research is limited by several methodological
      issues. Further studies with larger sample sizes and more sophisticated design
      are required to provide convincing evidence of a causal relationship between
      omega-3 PUFA and depression.

PMID- 20041819
TI  - PUFA for prevention and treatment of dementia?
AB  - Polyunsaturated fatty acids (PUFA) play a crucial role in cerebral structure and
      function. Omega-3 PUFA is an exciting area of research, with docosahexaenoic acid
      (DHA) emerging as a new potential agent for prevention of cognitive decline and
      treatment of Alzheimer's disease. Preclinical studies suggest that DHA maintains
      membrane fluidity, improves synaptic and neurotransmitter functioning, enhances
      learning and memory performances and displays neuroprotective properties. Several
      epidemiological studies supported the association between Omega-3 PUFA
      consumption and a lower prevalence of dementia. Although data are divergent, a
      growing body of evidence supports the view that regular consumption of dietary
      fish and seafood (which are rich in omega-3 PUFA) prevents cognitive decline.
      Finally, at present, few data are available from randomized clinical trials
      (RCTs). on the association between cognition and Omega-3. Ongoing RCTs that
      assess the effect of Omega-3 might provide new evidence on prevention and
      treatment of dementia. In this review, we summarize preclinical and clinical
      research suggesting that DHA exerts beneficial effects on cognitive function with
      ageing.

PMID- 20041820
TI  - PUFA for human health: diet or supplementation?
AB  - Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) are used to treat several diseases including
      hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from
      food, particularly from fatty fish. This review presents the literature examining
      the differences between omega-3 fatty acid dietary supplementation and prescribed
      omega-3-acid ethyl esters (P-OM3). Reports published between 1995 and 2007
      containing sources, recommended intake, and differences in the various
      formulations of omega-3 fatty acids were sought in PubMed and the Food and Drug
      Administration (FDA) Websites. However, lack of head-to-head clinical trials
      using both P-OM3 and dietary-supplement omega-3 fatty acids is the greatest
      limitation of this review. Although many kinds of omega-3 fatty acid dietary
      supplements are available, the efficacy, quality, and safety of these products
      are questionable because they are beyond any pharmaceutical control. Thus, P-OM3
      is the only FDA approved omega-3 fatty acid product which is available in the
      United States as an adjunct to diet to improve human health.

PMID- 20041821
TI  - Muscle development and regeneration in normal and pathological conditions:
      learning from Drosophila.
AB  - The recent demonstration that, throughout evolution, many molecular mechanisms
      have been highly conserved is fundamental to the advancement of our knowledge on
      muscle development and regeneration. Research has provided new insights into
      genetic cascades governing early steps of embryonic myogenesis and the
      regeneration of adult muscle in normal and pathological conditions, thus
      revealing significant similarity of both processes. Here we provide a current
      view on genetic mechanisms underlying muscle regeneration with a special focus on
      regeneration processes that take place in diseased and aging human muscle.
      Through examples of Drosophila models of human muscular diseases, we discuss
      potential impact they might have on uncovering molecular bases and identifying
      new treatments of muscle disorders. Taking advantage of evolutionarily conserved
      aspects of muscle development and the relative ease by which molecular pathways
      can be uncovered and dissected in a simple animal model, the fruit fly, we
      provide a comprehensive analysis of muscle development in Drosophila.
      Importantly, identification of muscle stem cell like adult muscle precursors in
      Drosophila makes fruit fly an attractive model system for studying muscle stem
      cell biology and muscle regeneration. In support of this assumption, recent
      studies in our laboratory provide arguments that important insights into the
      biology of vertebrate muscle stem cells can be gained from genetic analysis in
      Drosophila.

PMID- 20041822
TI  - Plasticity and physiological role of stem cells derived from skeletal muscle
      interstitium: contribution to muscle fiber hyperplasia and therapeutic use.
AB  - Stem cells other than satellite cells that can give rise to primary myoblasts,
      which are able to form additional new fibers postnatally, are present in the
      interstitial spaces of skeletal muscle. These cells are sorted into CD34(+)/45(-)
      (Sk-34) and CD34(-)/45(-) (Sk-DN) cell fractions, and they are wholly (>99%)
      negative for Pax7 at initial isolation. Colony-forming units of these cells
      typically include non-adherent type myogenic cells, while satellite cells are
      known to be adherent in cell culture. In addition, both Pax7(-) and Pax7(+) cells
      are produced, depending on asymmetric cell division. A large number of myotubes
      are also formed in each colony, thus suggesting that putative Pax7(+) satellite
      cells also present in each colony. Interestingly, interstitial myogenic cells
      show basal lamina formation at early stages of myogenesis in response to various
      types of stimulation in compensatory enlarged muscle, a property that satellite
      cells do not possess in the parent fiber basal lamina cylinder. Basal lamina
      formation and production of satellite cells are essential before muscle fiber
      establishment in vivo. It is therefore likely that myogenic cells in skeletal
      muscle can be divided into two populations: 1) basal lamina-producing myogenic
      cells; and 2) basal lamina-non-producing myogenic cells. The latter population
      may be Pax7(+) satellite cells showing adherent capacity in cell culture, while
      the lamina-producing myogenic population derived from interstitial multipotent
      stem cells, which is predominant among Sk-34 and Sk-DN cells, plays a role in
      primary myoblast generation and shows non-adherent behavior in culture.
      Therefore, the physiological role of interstitial myogenic cells is as a source
      for new postnatal muscle fiber formation, and multinucleated muscle fibers
      (cells) are potentially formed clonally.

PMID- 20041823
TI  - Regeneration of mammalian skeletal muscle. Basic mechanisms and clinical
      implications.
AB  - Mammalian skeletal muscles can regenerate following injury and this response is
      mediated by a specific type of stem cell, the satellite cell. We review here the
      three main phases of muscle regeneration, including i) the initial inflammatory
      response and the dual role of macrophages as both scavengers involved in the
      phagocytosis of necrotic debris and promoters of myogenic differentiation, ii)
      the activation and differentiation of satellite cells and iii) the growth and
      remodeling of the regenerated muscle tissue. Nerve activity is required to
      support the growth of regenerated myofibers and the specification of muscle fiber
      types, in particular the activation of the slow gene program. We discuss the
      regeneration process in two different settings. Chronic degenerative diseases,
      such as muscular dystrophies, are characterized by repeated cycles of segmental
      necrosis and regeneration involving scattered myofibers. In these conditions the
      regenerative capacity of satellite cells becomes exhausted with time and fibrosis
      prevails. Acute traumatic injuries, such as strain injuries common in sport
      medicine, cause the rupture of large myofiber bundles leading to muscle
      regeneration and formation of scar tissue and new myotendinous junctions at the
      level of the rupture. Mechanical loading is essential for muscle regeneration,
      therefore, following initial immobilization to avoid the risk of reruptures,
      early remobilization is required to induce correct growth and orientation of
      regenerated myofibers. Finally, we discuss the causes of age-dependent decline in
      muscle regeneration potential and the possibility of boosting regeneration in
      aging muscle and in muscular dystrophies.

PMID- 20041824
TI  - Echinoderms: potential model systems for studies on muscle regeneration.
AB  - Organisms of the phylum Echinodermata show some of the most impressive
      regenerative feats within the animal kingdom. Following injury or self-induced
      autotomy, species in this phylum can regenerate most tissues and organs, being
      the regeneration of the muscular systems one of the best studied. Even though
      echinoderms are closely related to chordates, they are little known in the
      biomedical field, and therefore their uses to study pharmacological effects on
      muscle formation and/or regeneration have been extremely limited. In order to
      rectify this lack of knowledge, we describe here the echinoderm muscular systems,
      particularly the somatic and visceral muscle components. In addition, we provide
      details of the processes that are known to take place during muscle regeneration,
      namely dedifferentiation, myogenesis and new muscle formation. Finally, we
      provide the available information on molecular and pharmacological studies that
      involve echinoderm muscle regeneration. We expect that by making this information
      accessible, researchers consider the use of echinoderms as model systems for
      pharmacological studies in muscle development and regeneration.

PMID- 20041825
TI  - The leech: a novel invertebrate model for studying muscle regeneration and
      diseases.
AB  - We focused our studies on the leech, Hirudo medicinalis. This invertebrate has a
      relative anatomical simplicity and is a reliable model for studying a variety of
      basic events, such as tissue repair, which has a striking similarity with
      vertebrate responses. Hirudo is also a good invertebrate model to test the
      actions of drugs and gene products, since the responses evoked by the different
      stimuli are clear and easily detectable due to their small size and anatomical
      simplicity. Here we review the use of this invertebrate model to investigate
      muscle regeneration and the role of hematopoietic stem cells in this process. Our
      recent data, summarized in this review, demonstrate that the injection of an
      appropriate combination of the matrigel biopolymer supplemented with Vascular
      Endothelial Growth factor (VEGF) in the leech Hirudo medicinalis is a remarkably
      effective tool for isolating a specific population of hematopoietic/endothelial
      precursor cells, which in turn can differentiate in muscle cells. Thus leeches
      can be considered as a new emerging model for studying endothelial and
      hematopoietic precursors cells involved in muscle post-natal growth and
      regeneration processes.

PMID- 20041826
TI  - Skeletal muscle metabolism in the pathology and treatment of type 1 diabetes.
AB  - Type 1 diabetes is characterised by the absence of circulating insulin due to the
      autoimmune destruction of beta-cells in the pancreas. Patients are traditionally
      treated with multiple daily injections of exogenous insulin analogues. However,
      although these therapies improve quality of life, they are associated with the
      risk of hypoglycemic episodes and do not prevent the development of debilitating
      secondary complications. For these reasons, there is increasing demand for new
      therapies and preventions. One approach is the use of viral or non-viral gene
      therapy to modify skeletal muscle to produce and secrete insulin into the
      circulation and/or to increase muscle glucose uptake. Skeletal muscle is a
      desirable target tissue for the treatment of diabetes not only for its central
      role in whole body metabolism and glucose homeostasis, but also for its
      accessibility and amenability to many potential gene therapy technologies. Here,
      we review the basic metabolic principles of skeletal muscle in the absorptive and
      post-absorptive states at rest and during exercise and discuss how these
      processes are affected in type 1 diabetes. Finally, current viral and non-viral
      strategies for modification of skeletal muscle and their application to the
      treatment of type 1 diabetes are also presented.

PMID- 20041827
TI  - Splice modification to restore functional dystrophin synthesis in Duchenne
      muscular dystrophy.
AB  - In little more than a decade, induced exon skipping as a therapy to treat
      Duchenne muscular dystrophy (DMD) has progressed from a concept tested in vitro,
      to pre-clinical evaluation in mouse and dog models, and recent completion of
      Phase I clinical trials in man. There is no longer any doubt that antisense
      oligomers can redirect dystrophin gene processing and by-pass protein truncating
      mutations after direct injection into muscle. Proof-of-concept has been
      demonstrated in human dystrophic muscle, with trials in Leiden and London showing
      that two different oligomer chemistries can restore the reading-frame in selected
      DMD patients by excising dystrophin exon 51. Systemic delivery of both oligomer
      types into DMD patients has commenced with promising results but it remains to be
      established if this therapy will have measurable clinical benefits. Targeted
      removal of exon 51 will only be directly applicable to about one in ten DMD
      individuals, and the immediate challenges include development of appropriate and
      effective delivery regimens, and extending splice-switching therapies to other
      dystrophin gene lesions. The success of induced exon skipping has spawned a
      number of "fusion therapies", including vector-mediated dystrophin exon skipping
      and ex vivo viral delivery of splice-switching antisense molecules into myogenic
      stem cells, followed by implantation, which may address long term oligomer
      delivery issues. This review summarizes the pivotal events leading to the
      completion of the first proof-of-concept trials and speculates on some of the
      scientific, ethical, regulatory and commercial challenges facing targeted exon
      skipping for the treatment of DMD.

PMID- 20041828
TI  - Muscular dystrophies: histology, immunohistochemistry, molecular genetics and
      management.
AB  - Muscle degeneration and regeneration are two of the most evident pathological
      events characterizing muscular diseases and in particular muscular dystrophies.
      Muscular dystrophies are an heterogeneous group of hereditary diseases affecting
      both children and adults, and are characterized by muscle wasting and weakness.
      Until now at least 30 different genes have been associated with muscular
      dystrophies. They have been divided into several subgroups depending on the
      distribution of the muscle weakness. Thus, the histopathological markers of all
      these forms are dystrophic changes at the muscle biopsy characterized by fiber
      size variability, fibres necrosis, regeneration, inflammation and connective
      tissues deposition. As for now, no effective therapy is available for these
      diseases but new inside has now been expanded in regenerative therapy such as
      cell therapy and gene therapy. This review is focused on muscular dystrophies and
      new acknowledgments in regenerative therapy.

PMID- 20041829
TI  - Skeletal myoblasts for heart regeneration and repair: state of the art and
      perspectives on the mechanisms for functional cardiac benefits.
AB  - Until recently, skeletal myoblasts (SkMBs) have been the most widely used cells
      in basic research and clinical trials of cell based therapy for cardiac repair
      and regeneration. Although SkMB engraftment into the post-infarcted heart has
      been consistently found to improve cardiac contractile function, the underlying
      therapeutic mechanisms remain still a matter of controversy and debate. This is
      basically because SkMBs do not attain a cardiac-like phenotype once homed into
      the diseased heart nor they form a contractile tissue functionally coupled with
      the surrounding viable myocardium. This issue of concern has generated the idea
      that the cardiotropic action of SkMBs may depend on the release of paracrine
      factors. However, the paracrine hypothesis still remains ill-defined,
      particularly concerning the identification of the whole spectrum of cell-derived
      soluble factors and details on their cardiac effects. In this context, the
      possibility to genetically engineering SkMBs to potentate their paracrine
      attitudes appears particularly attractive and is actually raising great
      expectation. Aim of the present review is not to cover all the aspects of cell
      based therapy with SkMBs, as this has been the object of previous exhaustive
      reviews in this field. Rather, we focused on novel aspects underlying the
      interactions between SkMBs and the host cardiac tissues which may be relevant for
      directing the future basic and applied research on SkMB transplantation for post
      ischemic cardiac dysfunction.

PMID- 20041830
TI  - Peganum harmala L. differentially modulates cytochrome P450 gene expression in
      human hepatoma HepG2 cells.
AB  - Peganum harmala L. (Zygophyllaceae) is a common plant in Middle East and it is
      still used traditionally to treat several diseases. The effect of P. harmala
      extract on the expression of different cytochrome P450's (CYP) involved in drug
      metabolism was examined in human HepG2 cells. Therefore, HepG2 cells were
      incubated with increasing concentrations of plant extract and the CYP gene
      expression was determined by real-time PCR. Our results showed that P. harmala
      extract significantly increased the expression of CYP1A2, 2C19, and 3A4 whereas;
      CYP 2B6, 2D6 and 2E1 was significantly decreased. We concluded that care should
      be taken when P. harmala is co-administered with other drugs.

PMID- 20041831
TI  - Cloning, expression, and characterization of CYP3A43 cDNA in cynomolgus macaque
      (Macaca fascicularis).
AB  - Cynomolgus macaques are frequently used in drug metabolism studies due to their
      evolutionary closeness to humans. Despite their importance, genes encoding drug
      metabolizing enzymes have not been fully identified in this species. In this
      study, the cDNA orthologous to human cytochrome P450 3A43 (CYP3A43) was isolated.
      Deduced amino acids of this cDNA had a high sequence identity ( approximately
      95%) to human CYP3A43 cDNA and contained characteristic motifs for CYP3A
      proteins, heme-binding region and substrate recognition sites. Among 10 tissues
      analyzed, cynomolgus CYP3A43 was expressed in liver, adrenal gland, and lung,
      with the highest expression seen in liver. Cynomolgus CYP3A43 protein
      heterologously expressed in Escherichia coli exhibited metabolic activity toward
      midazolam 1'-hydroxylation. These results indicated that cynomolgus CYP3A43 was
      expressed in liver and encoded a functional drug-metabolizing enzyme, and could
      contribute to overall drug metabolism in cynomolgus macaque liver if expressed as
      a protein.

PMID- 20041832
TI  - Prediction of human hepatic clearance using an in vitro plated hepatocyte
      clearance model.
AB  - Previously we have used human hepatocytes in suspension by measuring the parent
      loss for prediction of metabolic clearance according to a 1(st)-order kinetic
      model. In this study, we evaluated a novel integrative approach using plated
      human hepatocytes to include both uptake processes and metabolism in a single
      assay. Test articles were added in the medium, and the intrinsic clearance was
      determined based on the disappearance of the parent compound from the medium.
      Three different methods: direct, well-stirred, and parallel tube were tested for
      scaling purpose. With 30 randomly selected compounds with clinical clearance
      data, the scaled clearance showed reasonable linear correlation with r(2) values
      of 0.67, 0.72, and 0.70 for direct, well-stirred and parallel tube models,
      respectively. When human serum albumin (HSA) was added to the incubation medium a
      shift to lower in vitro clearance was observed for most of the compounds,
      suggesting that protein binding may have an effect on the metabolic clearance. In
      the presence of 4% of HSA, which is equivalent to the albumin concentration in
      the human plasma, the in vitro clearance data have the best prediction of human
      clearance when using the well-stirred method, followed by the parallel tube
      method and direct method. This study demonstrates the utility of using plated
      human hepatocyte as an integrated system for the prediction of human metabolic
      clearance. In addition, evaluation of the protein binding shift in the clearance
      showed that a significant number of compounds may not follow the equilibrium
      assumption according to the well-stirred model.

PMID- 20041833
TI  - Germatranyl substituted organotin (IV) carboxylates: synthesis spectroscopic
      characterization and biological activities.
AB  - Eight new organotin (IV) derivatives of general formula
      [N(CH2CH2O)3GeCH(R1)CH2COO](4-n)SnR(2)n, where n= 2, R(2) = C2H5 (1-5); R(1) =
      CH3 (1); C6H5 (2); p-CH3C6H4 (3); p-FC6H4(4); p-CH3OC6H4 (5) and n = 3, R(2) =
      CH2C6H5 (6-8), R(1) = CH3 (6); C6H5 (7); p-CH3C6H4 (8) have been synthesized by
      the reaction of di- or tri-organotin chloride with the corresponding germatranyl
      (substituted) propionic acid in the appropriate mole ratios using triethylamine
      as a base. The synthesized compounds were characterized by various spectroscopic
      techniques such as IR, multi-nuclear (1H, 13C, 119Sn) NMR, 119mSn Mossbauer,
      along with elemental analyses. They were also screened for in vitro anti
      leishmanial activity against promastigotes of leishmania donovani and found some
      encouraging results.

PMID- 20041834
TI  - Synthesis, cytotoxic evaluation and in silico pharmacokinetic prediction of some
      benzo[a]phenazine-5-sulfonic acid derivatives.
AB  - Cancer is one of the life threatening diseases and the development of novel
      anticancer molecules is limited by many reasons. In the present investigation,
      some novel benzo[a]phenazine-5-sulfonic acid derivatives as DNA intercalator was
      designed with optimized pharmacokinetic features for cancer treatment. The
      compounds with desired pharmacokinetic profile were synthesized and structurally
      characterized. Cytotoxic activity study against HL-60 tumor cell lines shows that
      10-dimethyl carboxamido derivative of benzo[a]phenazine-5-sulfonic acid is found
      to be the most active in the series with cytotoxic activity (IC(50) = 19 microM)
      comparable to cisplatin (IC(50) = 7 microM). The study concluded that the novel
      benzo[a]phenazine-5-sulfonic acid derivatives were found to have enhanced DNA
      binding affinity and exhibited significant activity in vitro against HL-60 cell
      lines. This work will also guide for further development of effective DNA
      intercalators for cancer treatment.

PMID- 20041835
TI  - Effect of polyphenolic compounds from Solanum torvum on plasma lipid
      peroxidation, superoxide anion and cytochrome P450 2E1 in human liver microsomes.
AB  - Previous studies presented evidence that plants contain antioxidants that have
      free radical-scavenging properties. Overproduction of free radicals leads to
      oxidative stress, a factor associated with a variety of diseases, such as
      diabetes. Cytochrome P450 2E1 enzymes (CYP2E1) are involved in drug metabolism in
      the liver and metabolism of DNA-reaction generating intra-mitochondrial ROS,
      which leads to micro- and macro-vascular pathology in diabetes. Plant-based
      chemicals can affect CYP2E1 enzymes and related defense mechanisms, possibly
      leading to protection against oxidative stress. We investigated the effect of
      Solanum torvum (ST) extracts on the inhibition of CYP2E1 activity in human liver
      microsomes. ST extract was analyzed for antioxidant activity by the ABTS method.
      Polyphenolic compounds were measured by the total phenol content using the Folin
      Ciocalteau reagent. Flavonoid and tannin content were analyzed by standard
      methods. Oxidative stress was evaluated by measuring lipid peroxidation by TBARS
      and superoxide anion scavenging levels in plasma from diabetic patients. Results
      showed that 10 mg/ml of ST had CYP2E1 catalytic inhibiting activity (57.16 %).
      The IC50 value of CYP2E1 catalytic inhibiting activity level was 5.14 mg/ml by
      concentration in a dependent manner. One gram of concentrated ST extract had an
      antioxidant activity index of 3.68 mg of trolox and 360.53 mg of ascorbic acid
      equivalent. Effects on free radical-scavenging, as measured by TBARS and
      superoxide anion, showed IC50 values of 20.60 and 10.26 microg/ml, respectively.
      Polyphenolic compounds found included phenol, flavonoid and tannin, measuring
      160.30, 104.36 and 65.91 mg/g, respectively. These results imply that ST is a
      natural source of polyphenolic antioxidants, which have cytochrome P450 2E1
      enzyme inhibiting and free radical scavenging properties, as related to lipid
      peroxidation and superoxide anion activity. ST could potentially be used for
      reducing oxidative stress in diabetes. Study for usage as a conventional
      medicine, including dosage and chronic toxicity in humans, should be pursued.

PMID- 20041836
TI  - Mechanisms involved in the genesis of diabetic nephropathy.
AB  - In recent years, the amount of people suffering from diabetes has increased
      notably. This increase has led to an augmentation in secondary diseases; amongst
      them, diabetic nephropathy (DN) is one of the most relevant pathologies. DN
      provokes a decrease in glomerular filtration rate, which ends up in chronic renal
      failure. In the developed countries, DN is the first cause of chronic renal
      failure needing replacement therapy. Thus, this disease is responsible for a
      remarkable part of the public health costs in the Western countries. All of these
      facts have encouraged many scientists to perform their research on mechanism
      causing DN, improving our knowledge of its pathogenesis. In this review we
      summarize the most relevant facts on the physiopathology of DN.

PMID- 20041837
TI  - A case of ischemic stroke in acute promyelocytic leukemia at initial
      presentation. Relevance of all-trans retinoic acid treatment.
AB  - Acute promyelocytic leukemia (APL) is frequently associated, often from the
      earliest phases, with a life-threatening coagulation/bleeding syndrome;
      disseminated intravascular coagulation (DIC) is described in majority of
      patients. We report a case of 49-year-old male, without cardiovascular risk
      factors, who suddenly developed ischemic stroke and splenic infarction as
      presenting symptoms of APL and related DIC. The patient was immediately treated
      with all-trans retinoic acid (ATRA) and the alterations of hemocoagulation
      parameters promptly returned in normal range. The coagulation/bleeding syndrome
      of the onset of APL is associated with high mortality; both diagnostic and
      therapeutic approaches require special and timely consideration of this
      condition. Treatment with ATRA is essential.

PMID- 20041839
TI  - Cardiovascular disease: what's all the AGE/RAGE about?
AB  - Advanced glycation end-products (AGEs) are involved in mediating the effects of
      hyperglycaemia in diabetes. The most important receptor for AGEs is the receptor
      for advanced glycation end-products (RAGE). Binding of AGEs to RAGE converts
      transient cellular stimulation into sustained cellular dysfunction driven by long
      term activation of the pro-inflammatory transcription factor NF-kB. Different
      splice variants of RAGE exist, including a soluble form that binds to AGEs but
      lacks the intracellular domain and thus fails to induce signal transduction. In
      this context, soluble RAGE may act as a therapeutic agent for AGE-induced
      effects. The balance between the synthesis of sRAGE and full-length RAGE may be
      an important determinant of AGE-induced dysfunction. An increasing amount of
      evidence suggests that AGEs either directly or via their interaction with RAGE
      play a pivotal role in the development and acceleration of atherosclerotic
      cardiovascular disease. These effects will be summarised in this review, together
      with the effects of therapeutic strategies targeting AGE/RAGE interactions. These
      treatments appear to have significant clinical potential, most likely in
      combination with currently used agents such as inhibitors of the renin
      angiotensin system or statins, to reduce the major burden of diabetes, its
      associated cardiovascular disease.

PMID- 20041840
TI  - Clopidogrel-proton pump inhibitor interaction: a primer for clinicians.
AB  - The European Medicines Agency (EMEA) recently issued a public statement on a
      possible interaction between clopidogrel and proton pump inhibitors (PPIs) and
      recommended that the product information for all medicines containing clopidogrel
      be amended to discourage concomitant use of PPIs unless absolutely necessary.
      This follows a prior alert issued by the United States Food and Drug
      Administration (FDA) earlier this year, stating that PPIs might interfere with
      the effectiveness of clopidogrel and that clinicians should reevaluate starting
      or continuing treatment with a PPI in patients taking clopidogrel. However,
      several experts have voiced their concern that the clopidogrel-PPI interaction
      has been given undue importance, given that all clinical studies suggesting this
      problem are observational. In this review, we critically analyze the available
      data and make practical suggestions for the clinician regarding appropriate use
      of PPIs in patients receiving clopidogrel. Based on currently available evidence,
      we suggest that the decision to prescribe a PPI to a patient on clopidogrel must
      be made on an individual patient basis balancing the gastrointestinal risk with
      the possible thrombotic risk and that PPIs should only be used for truly
      appropriate indications.

PMID- 20041841
TI  - Amiodarone - a 'broad spectrum' antiarrhythmic drug.
AB  - Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti
      anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is
      currently one of the most commonly prescribed drugs in US for ventricular and
      atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic
      agent, it also has class I, II, IV actions, making it a unique and effective anti
      arrhythmic agent. Because of its minimal negative inotropic activity and very low
      rate of pro-arrhythmia, it is considered safe in treating arrhythmias in patients
      with Coronary Artery Disease and Left ventricular systolic dysfunction. Despite
      these advantages, long term oral therapy with amiodarone is limited by side
      effect profile involving various organs like thyroid, lung, heart, liver, skin
      etc. Though the side effects can be decreased significantly by keeping the
      maintenance dose at 200 to 300 mg/day, patients on amiodarone should be followed
      closely. Amiodarone interacts with medications such as Warfarin, Digoxin,
      Macrolides, Floroquinolones etc., which share Cytochrome P450 metabolic pathway.
      Hence reducing their doses prior to starting amiodarone is recommended.
      Amiodarone, a category D drug, is contraindicated in pregnant and breast feeding
      women. This review discusses the pharmacokinetics of amiodarone, its evolving
      clinical indications, management of toxicity and drug interactions.

PMID- 20041838
TI  - Risk factors and mediators of the vascular dysfunction associated with
      hypertension in pregnancy.
AB  - Normal pregnancy is associated with significant hemodynamic changes and
      vasodilation in the uterine and systemic circulation in order to meet the
      metabolic demands of the mother and developing fetus. Hypertension in pregnancy
      (HTN-Preg) and preeclampsia (PE) are major complications and life-threatening
      conditions to both the mother and fetus. PE is precipitated by various genetic,
      dietary and environmental factors. Although the initiating events of PE are
      unclear, inadequate invasion of cytotrophoblasts into the uterine artery is
      thought to reduce uteroplacental perfusion pressure and lead to placental
      ischemia/hypoxia. Placental hypoxia induces the release of biologically active
      factors such as growth factor inhibitors, anti-angiogenic proteins, inflammatory
      cytokines, reactive oxygen species, hypoxia-inducible factors, and antibodies to
      vascular angiotensin II receptor. These bioactive factors affect the
      production/activity of various vascular mediators in the endothelium, smooth
      muscle and extracellular matrix, leading to severe vasoconstriction and HTN. As
      an endothelial cell disorder, PE is associated with decreased vasodilator
      mediators such as nitric oxide, prostacyclin and hyperpolarizing factor and
      increased vasoconstrictor mediators such as endothelin, angiotensin II and
      thromboxane A(2). PE also involves enhanced mechanisms of vascular smooth muscle
      contraction including intracellular free Ca(2+) concentration ([Ca(2+)](i)), and
      [Ca(2+)](i) sensitization pathways such as protein kinase C, Rho-kinase and
      mitogen-activated protein kinase. Changes in extracellular matrix composition and
      matrix metalloproteases activity also promote vascular remodeling and further
      vasoconstriction in the uterine and systemic circulation. Characterization of the
      predisposing risk factors, the biologically active factors, and the vascular
      mediators associated with PE holds the promise for early detection, and should
      help design specific genetic and pharmacological tools for the management of the
      vascular dysfunction associated with HTN-Preg.

PMID- 20041842
TI  - Human arylamine N-acetyltransferase 1: a drug-metabolizing enzyme and a drug
      target?
AB  - Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic
      metabolizing enzyme (XME) involved in the biotransformation of many aromatic and
      heterocyclic amines. This XME plays key roles in both the detoxification and/or
      bioactivation of numerous drugs and carcinogens. NAT1 is polymorphic and displays
      a large tissue distribution. NAT1 activity have been extensively studied because
      of its potential role in the biotransformation of important carcinogens. Several
      recent studies suggest that NAT1 may have a role in breast cancer progression.
      Indeed, this XME has been shown to affect the growth and drug resistance of
      breast cancer cells and appears as a marker in human estrogen receptor positive
      breast cancer. In addition, it has been shown that this enzyme is inhibited in
      vivo by cancer drugs such as cisplatin or tamoxifen. Recent published data
      suggest that NAT1 could be of therapeutic interest for cancer. We provide here an
      overview on the putative involvement of NAT1 in cancer and its possible role as a
      drug target.

PMID- 20041843
TI  - The use of major analgesics in patients with renal dysfunction.
AB  - Pain in patients with impaired renal function may be a significant problem
      requiring treatment with opioids. However, pharmacokinetic and metabolic changes
      associated with an impaired renal function may raise some concerns about side
      effects and overdosing associated with opioid agents in this patient's
      population. In order to give recommendations on this issue, we review the
      available evidences on the pharmacokinetics and side effects of most common
      opioids used to treat pain. The results of this review show that the half-life of
      the parent opioid compounds and of their metabolites is increased in the presence
      of renal dysfunction, for which careful monitoring of the patient, dose reduction
      and a longer time interval between doses are recommended. Among opioids, morphine
      and codeine used with very caution and possibly avoided in renal failure/dialysis
      patients; tramadol, hydromorphone and oxycodone can be used with caution and
      close patient's monitoring, whereas transdermal buprenorphine, methadone and
      fentanyl/sufentanil appear to be safe to use in patients with renal failure.

PMID- 20041845
TI  - A device for the simple and rapid transcervical transfer of mouse embryos
      eliminates the need for surgery and potential post-operative complications.
AB  - We describe a novel device that can be used for the transcervical transfer of
      embryos into pseudopregnant female mice. This nonsurgical embryo transfer (NSET)
      device is as efficient as standard surgical embryo transfer in the production of
      transgenic mice, and can also be used for the transfer of embryonic stem cell
      containing chimeric blastocysts and cryopreserved embryos. In addition to the
      elimination of surgery, recipient females do not have to be anesthetized. The
      NSET device eliminates a painful surgical procedure as well as potential
      complications associated with anesthesia/post-operative care, reduces the
      technical expertise and equipment needed for surgical transfer, and represents
      substantial cost savings and regulatory reduction. NSET technology provides an
      easy and rapid alternative to surgical embryo transfer. Address correspondence to
      Brett Spear, Room 210, Combs Building, University of Kentucky College of
      Medicine, 800 Rose Street, Lexington, KY, 40536-0298, USA. email:

PMID- 20041846
TI  - Use and validation of epithelial recognition and fields of view algorithms on
      virtual slides to guide TMA construction.
AB  - While tissue microarrays (TMAs) are a form of high-throughput screening, they
      presently still require manual construction and interpretation. Because of
      predicted increasing demand for TMAs, we investigated whether their construction
      could be automated. We created both epithelial recognition algorithms (ERAs) and
      field of view (FOV) algorithms that could analyze virtual slides and select the
      areas of highest cancer cell density in the tissue block for coring (algorithmic
      TMA) and compared these to the cores manually selected (manual TMA) from the same
      tissue blocks. We also constructed TMAs with TMAker, a robot guided by these
      algorithms (robotic TMA). We compared each of these TMAs to each other. Our
      imaging algorithms produced a grid of hundreds of FOVs, identified cancer cells
      in a stroma background and calculated the epithelial percentage (cancer cell
      density) in each FOV. Those with the highest percentages guided core selection
      and TMA construction. Algorithmic TMA and robotic TMA were overall approximately
      50% greater in cancer cell density compared with Manual TMA. These observations
      held for breast, colon, and lung cancer TMAs. Our digital image algorithms were
      effective in automating TMA construction.

PMID- 20041844
TI  - The role of Notch signaling pathway in epithelial-mesenchymal transition (EMT)
      during development and tumor aggressiveness.
AB  - The Notch signaling pathway maintains a balance between cell proliferation and
      apoptosis, and thus it is believed that Notch signaling pathways may play an
      important role in the development and progression of several malignancies.
      However, the functions of Notch signaling in EMT are largely unknown. This mini
      review describes the role of Notch signaling pathway in EMT, and cataloging how
      its deregulation is involved in EMT and tumor aggressiveness. Further attempts
      have been made to summarize the role of several chemopreventive agents that could
      be useful for targeted inactivation of Notch signaling, and thus it may cause
      reversal of EMT, which could become a novel approach for cancer prevention and
      treatment.

PMID- 20041847
TI  - A quantitative approach to detect and overcome PCR inhibition in ancient DNA
      extracts.
AB  - Inhibition is problematic in many applications of PCR, particularly those
      involving degraded or low amounts of template DNA, when simply diluting the
      extract is undesirable. Two basic approaches to monitoring inhibition in such
      samples using real-time or quantitative PCR (qPCR) have been proposed. The first
      method analyzes the quantification cycle (Cq) deviation of a spiked internal
      positive control. The second method considers variations in reaction efficiency
      based on the slopes of individual amplification plots. In combining these
      methods, we observed increased Cq values together with reduced amplification
      efficiencies in some samples, as expected; however, deviations from this pattern
      in other samples support the use of both measurements. Repeat inhibition testing
      enables optimization of PCR facilitator combinations and sample dilution such
      that DNA yields and/or quantitative accuracy can be maximized in subsequent PCR
      runs. Although some trends were apparent within sample types, differences in
      inhibition levels, optimal reactions conditions, and expected recovery of DNA
      under these conditions suggest that all samples be routinely tested with this
      approach.

PMID- 20041848
TI  - Improved forensic DNA analysis through the use of alternative DNA polymerases and
      statistical modeling of DNA profiles.
AB  - DNA evidence, linking perpetrators to crime scenes, is central to many legal
      proceedings. However, DNA samples from crime scenes often contain PCR-inhibitory
      substances, which may generate blank or incomplete DNA profiles. Extensive DNA
      purification can be required to rid the sample of these inhibitors, although
      these procedures increase the risk of DNA loss. Most forensic laboratories use
      commercial DNA amplification kits (e.g., AmpFlSTR SGM Plus) with the DNA
      polymerase AmpliTaq Gold as the gold standard. Here, we show that alternative DNA
      polymerase-buffer systems can improve the quality of forensic DNA analysis and
      efficiently circumvent PCR inhibition in crime scene samples, without additional
      sample preparation. DNA profiles from 20 of 32 totally or partially inhibited
      crime scene saliva samples were significantly improved using Bio-X-Act Short,
      ExTaq Hot Start, or PicoMaxx High Fidelity instead of AmpliTaq Gold. A
      statistical model for unbiased quality control of forensic DNA profiles was
      developed to quantify the results. Our study demonstrates the importance of
      adjusting the chemistry of the PCR to enhance forensic DNA analysis and
      diagnostic PCR, providing an alternative to laborious sample preparation
      protocols.

PMID- 20041849
TI  - Cytoplasmic injection of circular plasmids allows targeted expression in
      mammalian embryos.
AB  - Injection of linearized DNA constructs into the pronuclei of fertilized mammalian
      eggs is a standard method for producing transgenic embryos and animals. Here, we
      show that injection of covalently closed circular (ccc) plasmids into the
      cytoplasm of fertilized bovine and murine eggs is a highly efficient and simple
      alternative for ectopic expression of foreign DNA in embryos. A broad range of
      plasmids could be successfully expressed in preimplantation stages, including
      plasmids and minicircles with a scaffold/matrix attachment region (S/MAR),
      conventional plasmids, and bacterial artificial chromosomes (BACs). Although the
      foreign DNA plasmids are mainly maintained as episomal entities during
      preimplantation development, they accurately behave like nuclear DNA. Onset of
      transcription of an Oct4 promoter-controlled marker gene coincided with the
      species-specific time points of major embryonic genome activation, and could be
      modulated by in vitro DNA-methylation. This approach allows an experimental
      access to reprogramming events in early mammalian embryos.

PMID- 20041850
TI  - Simplified DGS procedure for large-scale genome structural study.
AB  - Ditag genome scanning (DGS) uses next-generation DNA sequencing to sequence the
      ends of ditag fragments produced by restriction enzymes. These sequences are
      compared to known genome sequences to determine their structure. In order to use
      DGS for large-scale genome structural studies, we have substantially revised the
      original protocol by replacing the in vivo genomic DNA cloning with in vitro
      adaptor ligation, eliminating the ditag concatemerization steps, and replacing
      the 454 sequencer with Solexa or SOLiD sequencers for ditag sequence collection.
      This revised protocol further increases genome coverage and resolution and allows
      DGS to be used to analyze multiple genomes simultaneously.

PMID- 20041851
TI  - A neurite quality index and machine vision software for improved quantification
      of neurodegeneration.
AB  - Current methods to assess neurodegradation in dorsal root ganglion cultures as a
      model for neurodegenerative diseases are imprecise and time-consuming. Here we
      describe two new methods to quantify neuroprotection in these cultures. The
      neurite quality index (NQI) builds upon earlier manual methods, incorporating
      additional morphological events to increase detection sensitivity for the
      detection of early degeneration events. Neurosight is a machine vision-based
      method that recapitulates many of the strengths of NQI while enabling high
      throughput screening applications with decreased costs.

PMID- 20041852
TI  - A transfer-less, multi-well liquid culture feeding system for screening small
      molecules that affect the longevity of Caenorhabditis elegans.
AB  - Agricultural sciences rely almost entirely on chemical assays to screen the
      thousands of crop cultivars generated in a crop improvement program for potential
      human health benefits. This situation exists in part because most animal models
      are expensive to implement, utilize large amounts of plant material, and require
      specialized facilities and technical training. A cost-effective, high-throughput
      animal model to screen crop extracts for small molecules with biological activity
      related to human health benefits would provide a much-needed resource. Here we
      introduce a new, relatively high-throughput method incorporating the microscopic
      Caenorhabditis elegans nematode, which is suitable for screening chemical
      extracts for bioactivity without the need for robotics. This system was chosen
      because longevity extension in C. elegans has been previously associated with
      human health benefits. Through the use of cell culture inserts, C. elegans can be
      exposed to fresh crop extracts daily throughout their lifespan without mechanical
      manipulation of the worm, thus minimizing stress and creating an environment
      suitable for experiments measuring longevity. Additionally, the duration of
      longevity experiments can be reduced by using type II right censoring in
      experimental design and survival analyses.

PMID- 20041853
TI  - Nucleic acid contamination of glycogen used in nucleic acid precipitation and
      assessment of linear polyacrylamide as an alternative co-precipitant.
AB  - Molecular-grade glycogen is widely used to recover nanogram or picogram
      quantities of DNA and RNA across molecular biology applications in the life
      sciences. As a result, its purity is critical to obtain reliable results. Using
      agarose gel electrophoresis, we detected pg/microL (DNA) to ng/microL (RNA)
      concentrations of nucleic acid in two of the nine glycogen samples obtained from
      commercial suppliers. Denaturing gradient gel electrophoresis of 16S rRNA gene
      PCR-amplified products indicated that an additional two samples contained
      detectable contamination. We also tested a synthetic polymer co-precipitant,
      linear polyacrylamide (LPA); none of the four samples tested with LPA were
      detectably contaminated. The partial 16S rRNA gene sequence associated with the
      contaminated samples of the shellfish-derived glycogen was nearly identical to
      the sequence of Actinobacteria lwoffii, which has been isolated from mussels
      previously. By testing the recovery of low-nanogram amounts of DNA with multiple
      precipitants and simulated experimental conditions, we demonstrated that LPA was
      a preferable co-precipitant for sensitive protocols.

PMID- 20041854
TI  - Comparison of multiplex ligation-dependent probe amplification and real-time PCR
      accuracy for gene copy number quantification using the beta-defensin locus.
AB  - The reliable quantification of gene copy number variations is a precondition for
      future investigations regarding their functional relevance. To date, there is no
      generally accepted gold standard method for copy number quantification, and
      methods in current use have given inconsistent results in selected cohorts. In
      this study, we compare two methods for copy number quantification. beta-defensin
      gene copy numbers were determined in parallel in 80 genomic DNA samples by real
      time PCR and multiplex ligation-dependent probe amplification (MLPA). The
      pyrosequencing-based paralog ratio test (PPRT) was used as a standard of
      comparison in 79 out of 80 samples. Realtime PCR and MPLA results confirmed
      concordant DEFB4, DEFB103A, and DEFB104A copy numbers within samples. These two
      methods showed identical results in 32 out of 80 samples; 29 of these 32 samples
      comprised four or fewer copies. The coefficient of variation of MLPA is lower
      compared with PCR. In addition, the consistency between MLPA and PPRT is higher
      than either PCR/MLPA or PCR/PPRT consistency. In summary, these results suggest
      that MLPA is superior to real-time PCR in beta-defensin copy number
      quantification.

PMID- 20041855
TI  - Engineering a novel endopeptidase based on SARS 3CL(pro).
AB  - A 3C-like protease (3CLpro) from the severe acute respiratory syndrome
      coronavirus (SARS-CoV) is required for viral replication, cleaving the replicase
      polyproteins at 11 sites with the conserved Gln [downward arrow](Ser, Ala, Gly)
      sequences. In this study, we developed a mutant 3CLpro (T25G) with an expanded
      S1' space that demonstrates 43.5-fold better k(cat)/K(m) compared with wild-type
      in cleaving substrates with a larger Met at P1' and is suitable for tag removal
      from recombinant fusion proteins. Two vectors for expressing fusion proteins with
      the T25G recognition site (Ala-Val-Leu-Gln [downward arrow]Met) in Escherichia
      coli and yeast were constructed. Identical cloning sites were used in these
      vectors for parallel cloning. PstI was chosen as a 5' cloning site because it
      overlapped the nucleotide sequence encoding the protease site and avoided
      addition of extra amino acids at the N terminus of recombinant proteins. 3CL(pro)
      (T25G) was found to have a 3-fold improvement over TEV(pro) in tag cleavage at
      each respective preferred cleavage site.

PMID- 20041856
TI  - ALISSA: an automated live-cell imaging system for signal transduction analyses.
AB  - Probe photobleaching and a specimen's sensitivity to phototoxicity severely limit
      the number of possible excitation cycles in time-lapse fluorescent microscopy
      experiments. Consequently, when a study of cellular processes requires
      measurements over hours or days, temporal resolution is limited, and spontaneous
      or rapid events may be missed, thus limiting conclusions about transduction
      events. We have developed ALISSA, a design framework and reference implementation
      for an automated live-cell imaging system for signal transduction analysis. It
      allows an adaptation of image modalities and laser resources tailored to the
      biological process, and thereby extends temporal resolution from minutes to
      seconds. The system employs online image analysis to detect cellular events that
      are then used to exercise microscope control. It consists of a reusable image
      analysis software for cell segmentation, tracking, and time series extraction,
      and a measurement-specific process control software that can be easily adapted to
      various biological settings. We have applied the ALISSA framework to the analysis
      of apoptosis as a demonstration case for slow onset and rapid execution
      signaling. The demonstration provides a clear proof-of-concept for ALISSA, and
      offers guidelines for its application in a broad spectrum of signal transduction
      studies.

PMID- 20041857
TI  - Tunable fractionation of nucleic acids.
AB  - We developed a method for selective purification of DNA using the cationic
      detergent, cetyltrimethylammonium bromide (CTAB), accompanied with urea and
      controlled high-salt (NaCl) concentration. This method is effective for rapid
      separation of DNA fragments from artifacts such as PCR primer dimers or ligation
      adapters. The CTAB-associated purification completely removed the short PCR
      artifacts and primers, as well as enzymes and buffer, while recovering a
      sufficient quantity of amplicons for subsequent experiments such as preparation
      of libraries. This method could also be applied to the fractionation of nucleic
      acids generated by other types of reactions.

PMID- 20041858
TI  - Neuroprotective effects of hydrogen sulfide on Parkinson's disease rat models.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a
      progressive loss of dopaminergic neurons in the substantia nigra (SN). The
      present study was designed to examine the therapeutic effect of hydrogen sulfide
      (H(2)S, a novel biological gas) on PD. The endogenous H(2)S level was markedly
      reduced in the SN in a 6-hydroxydopamine (6-OHDA)-induced PD rat model. Systemic
      administration of NaHS (an H(2)S donor) dramatically reversed the progression of
      movement dysfunction, loss of tyrosine-hydroxylase positive neurons in the SN and
      the elevated malondialdehyde level in injured striatum in the 6-OHDA-induced PD
      model. H(2)S specifically inhibited 6-OHDA evoked NADPH oxidase activation and
      oxygen consumption. Similarly, administration of NaHS also prevented the
      development of PD induced by rotenone. NaHS treatment inhibited microglial
      activation in the SN and accumulation of pro-inflammatory factors (e.g. TNF-alpha
      and nitric oxide) in the striatum via NF-kappaB pathway. Moreover, significantly
      less neurotoxicity was found in neurons treated with the conditioned medium from
      microglia incubated with both NaHS and rotenone compared to that with rotenone
      only, suggesting that the therapeutic effect of NaHS was, at least partially,
      secondary to its suppression of microglial activation. In summary, we demonstrate
      for the first time that H(2)S may serve as a neuroprotectant to treat and prevent
      neurotoxin-induced neurodegeneration via multiple mechanisms including anti
      oxidative stress, anti-inflammation and metabolic inhibition and therefore has
      potential therapeutic value for treatment of PD.

PMID- 20041859
TI  - Insights from comparative analyses of aging in birds and mammals.
AB  - Many laboratory models used in aging research are inappropriate for understanding
      senescence in mammals, including humans, because of fundamental differences in
      life history, maintenance in artificial environments, and selection for early
      aging and high reproductive rate. Comparative studies of senescence in birds and
      mammals reveal a broad range in rates of aging among a variety of taxa with
      similar physiology and patterns of development. These comparisons suggest that
      senescence is a shared property of all vertebrates with determinate growth, that
      the rate of senescence has been modified by evolution in response to the
      potential life span allowed by extrinsic mortality factors, and that most
      variation among species in the rate of senescence is independent of commonly
      ascribed causes of aging, such as oxidative damage. Individuals of potentially
      long-lived species, particularly birds, appear to maintain high condition to near
      the end of life. Because most individuals in natural populations of such species
      die of aging-related causes, these populations likely harbor little genetic
      variation for mechanisms that could extend life further, or these mechanisms are
      very costly. This, and the apparent evolutionary conservatism in the rate of
      increase in mortality with age, suggests that variation in the rate of senescence
      reflects fundamental changes in organism structure, likely associated with the
      rate of development, rather than physiological or biochemical processes
      influenced by a few genes. Understanding these evolved differences between long
      lived and short-lived organisms would seem to be an essential foundation for
      designing therapeutic interventions with respect to human aging and longevity.

PMID- 20041860
TI  - Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009.

PMID- 20041861
TI  - In response to: Testa et al. 'Elective surgical patients as living organ donors:
      a clinical and ethical innovation'.

PMID- 20041862
TI  - Impact of thrombocytopenia on survival of baboons with genetically modified pig
      liver transplants: clinical relevance.
AB  - A lack of deceased human donor livers leads to a significant mortality in
      patients with acute-on-chronic or acute (fulminant) liver failure or with primary
      nonfunction of an allograft. Genetically engineered pigs could provide livers
      that might bridge the patient to allotransplantation. Orthotopic liver
      transplantation in baboons using livers from alpha1,3-galactosyltransferase gene
      knockout (GTKO) pigs (n = 2) or from GTKO pigs transgenic for CD46 (n = 8) were
      carried out with a clinically acceptable immunosuppressive regimen. Six of 10
      baboons survived for 4-7 days. In all cases, liver function was adequate, as
      evidenced by tests of detoxification, protein synthesis, complement activity and
      coagulation parameters. The major problem that prevented more prolonged survival
      beyond 7 days was a profound thrombocytopenia that developed within 1 h after
      reperfusion, ultimately resulting in spontaneous hemorrhage at various sites. We
      postulate that this is associated with the expression of tissue factor on
      platelets after contact with pig endothelium, resulting in platelet and platelet
      peripheral blood mononuclear cell(s) aggregation and deposition of aggregates in
      the liver graft, though we were unable to confirm this conclusively. If this
      problem can be resolved, we would anticipate that a pig liver could provide a
      period during which a patient in liver failure could be successfully bridged to
      allotransplantation.

PMID- 20041863
TI  - Diabetes after kidney donation.
AB  - Kidney donors, similar to the general population, are at risk for development of
      type 2 diabetes mellitus (T2DM). The course of donors who develop T2DM has not
      been studied. We surveyed 3777 kidney donors regarding the development of T2DM.
      Of the 2954 who responded, 154 developed T2DM 17.7 +/- 9.0 years after donation.
      The multivariable risk of development of T2DM was associated with type 1 DM in
      the recipient, male gender and body mass index >30 kg/m(2) at time of donation.
      Compared to age, gender, duration after donation and body mass index (BMI)
      matched non-diabetic donor controls; diabetic donors were more likely to have
      hypertension (70.8% vs. 36.2%, p = 0.005), proteinuria (18.8% vs. 3.9%, p <
      0.0001) but had a similar serum creatinine. eGFR change after T2DM development
      was -0.80 +/- 0.94 mL/min/year, -0.70 +/- 0.86 in nondiabetic donors with similar
      duration after donation and -0.61 +/- 0.76 mL/min/year in age, gender, BMI and
      duration after donation matched nondiabetic donor controls. These preliminary and
      short-term data demonstrate that factors associated with T2DM in kidney donors
      are similar to those in the general population and donors screened carefully at
      the time of donation do not appear to have an acceleration of diabetic kidney
      disease.

PMID- 20041864
TI  - Histopathologic clusters differentiate subgroups within the nonspecific diagnoses
      of CAN or CR: preliminary data from the DeKAF study.
AB  - The nonspecific diagnoses 'chronic rejection''CAN', or 'IF/TA' suggest neither
      identifiable pathophysiologic mechanisms nor possible treatments. As a first step
      to developing a more useful taxonomy for causes of new-onset late kidney
      allograft dysfunction, we used cluster analysis of individual Banff score
      components to define subgroups. In this multicenter study, eligibility included
      being transplanted prior to October 1, 2005, having a 'baseline' serum creatinine
      < or =2.0 mg/dL before January 1, 2006, and subsequently developing deterioration
      of graft function leading to a biopsy. Mean time from transplant to biopsy was
      7.5 +/- 6.1 years. Of the 265 biopsies (all with blinded central pathology
      interpretation), 240 grouped into six large (n > 13) clusters. There were no
      major differences between clusters in recipient demographics. The actuarial
      postbiopsy graft survival varied by cluster (p = 0.002). CAN and CNI toxicity
      were common diagnoses in each cluster (and did not differentiate clusters).
      Similarly, C4d and presence of donor specific antibody were frequently observed
      across clusters. We conclude that for recipients with new-onset late graft
      dysfunction, cluster analysis of Banff scores distinguishes meaningful subgroups
      with differing outcomes.

PMID- 20041866
TI  - Composite tissue vasculopathy and degeneration following multiple episodes of
      acute rejection in reconstructive transplantation.
AB  - Transplant vasculopathy has not been systematically investigated in composite
      tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs)
      on long-term graft outcomes in reconstructive transplantation remains unknown.
      This study in a rat hind-limb allotransplantation model systematically analyzes
      vasculopathy and tissue-specific pathological changes secondary to multiple AR
      episodes. LEW rats were transplanted with BN rat hind limbs and treated as
      follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3
      (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in
      Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was
      completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group
      3 animals demonstrated significant vascular lesions along with skin and muscle
      atrophy, upregulation of profibrotic gene expression and fibrosis when compared
      to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to
      malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas
      muscle atrophy with macrophage infiltration was seen early, after only a few AR
      episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue
      specific pathology in CTA. This is the first evidence of 'composite tissue
      vasculopathy and degeneration (CTVD)' in CTA.

PMID- 20041865
TI  - The changed balance of regulatory and naive T cells promotes tolerance after TLI
      and anti-T-cell antibody conditioning.
AB  - The goal of the study was to determine how the changed balance of host naive and
      regulatory T cells observed after conditioning with total lymphoid irradiation
      (TLI) and antithymocyte serum (ATS) promotes tolerance to combined organ and bone
      marrow transplants. Although previous studies showed that tolerance was dependent
      on host natural killer T (NKT) cells, this study shows that there is an
      additional dependence on host CD4(+)CD25(+) Treg cells. Depletion of the latter
      cells before conditioning resulted in rapid rejection of bone marrow and organ
      allografts. The balance of T-cell subsets changed after TLI and ATS with TLI
      favoring mainly NKT cells and ATS favoring mainly Treg cells. Combined modalities
      reduced the conventional naive CD4(+) T cells 2800-fold. The host type Treg cells
      that persisted in the stable chimeras had the capacity to suppress alloreactivity
      to both donor and third party cells in the mixed leukocyte reaction. In
      conclusion, tolerance induction after conditioning in this model depends upon the
      ability of naturally occurring regulatory NKT and Treg cells to suppress the
      residual alloreactive T cells that are capable of rejecting grafts.

PMID- 20041867
TI  - Equivalent outcomes for pediatric heart transplantation recipients: ABO-blood
      group incompatible versus ABO-compatible.
AB  - ABO-blood group incompatible infant heart transplantation has had excellent short
      term outcomes. Uncertainties about long-term outcomes have been a barrier to the
      adoption of this strategy worldwide. We report a nonrandomized comparison of
      clinical outcomes over 10 years of the largest cohort of ABO-incompatible
      recipients. ABO-incompatible (n = 35) and ABO-compatible (n = 45) infant heart
      transplantation recipients (< or =14 months old, 1996-2006) showed no important
      differences in pretransplantation characteristics. There was no difference in
      incidence of and time to moderate acute cellular rejection. Despite either the
      presence (seven patients) or development (eight patients) of donor-specific
      antibodies against blood group antigens, in only two ABO-incompatible patients
      were these antibodies implicated in antibody-mediated rejection (which occurred
      early posttransplantation, was easily managed and did not recur in follow-up).
      Occurrence of graft vasculopathy (11%), malignancy (11%) and freedom from severe
      renal dysfunction were identical in both groups. Survival was identical (74% at 7
      years posttransplantation). ABO-blood group incompatible heart transplantation
      has excellent outcomes that are indistinguishable from those of the ABO
      compatible population and there is no clinical justification for withholding this
      lifesaving strategy from all infants listed for heart transplantation. Further
      studies into observed differing responses in the development of donor-specific
      isohemagglutinins and the implications for graft accommodation are warranted.

PMID- 20041869
TI  - Herpes simplex virus type-2 in Egyptian patients with bladder cancer or cystitis.
AB  - The present study was designed to investigate the prevalence of herpes simplex
      virus type-2 (HSV-2) in Egyptian patients with bladder cancer or cystitis and to
      evaluate the performance of different diagnostic HSV-2 assays. The study included
      50 patients: 27 with bladder cancer (group I), 23 with cystitis (group II) and 20
      subjects as controls (group III). HSV-2 DNA was detected using polymerase chain
      reaction (PCR) on bladder tissue and buffy coat cells (BCC). Electron microscopic
      studies (EMS) on BCC and ELISAs for IgM, IgG and specific glycoprotein G-2 (gG-2)
      IgG were performed. HSV-2 DNA was detected by PCR on bladder tissue biopsies in
      29.6% and 21.7% of group I and II respectively and it was also detected by PCR on
      BCC in 22.2% and 21.7% of group I and II respectively. EMS revealed HSV like
      particles in 16.6% of cases. IgG, specific gG-2 IgG and IgM were detected in 30%,
      16% and 6% of cases respectively. The different assays were evaluated in relation
      to PCR on bladder tissue biopsies. The gG-2-based ELISA and EMS on BCC were found
      to be highly specific (97.3% and 100% respectively), with similar low sensitivity
      of approximately 54%. PCR on BCC was the most sensitive assay. The association of
      HSV-2 with bladder cancer is suggested especially in schistosomal patients.

PMID- 20041870
TI  - Quantification of Chlamydia pneumoniae in cultured human macrophages and HL
      cells: comparison of real-time PCR, immunofluorescence and ELISA methods.
AB  - Chlamydia pneumoniae is an intracellular gram-negative bacterium, which
      replicates only in eukaryotic cells. Quantification of C. pneumoniae in cell
      culture is needed when studying e.g. the effect of drugs or host cell factors on
      infectivity and replication. Conventionally, this has been performed by
      immunofluorescence staining and microscopic counting of chlamydial inclusions.
      However, this method is usable only if the cell numbers do not fluctuate in cell
      culture vials and the inclusions are uniform. In macrophages, inclusions are
      often aberrant, their sizes vary, and multiple inclusions are also seen.
      Therefore, methods are needed to quantify exact amounts of C. pneumoniae in
      cells. Here, we describe a new method based on the real-time PCR quantification
      of chlamydial genomes adjusted to the number of human genomes in cultures. In
      human epithelial (HL) cell cultures, the C. pneumoniae inclusion numbers and the
      ratio of C. pneumonia genomes/human genome (Cpn/Hum) correlated significantly (r
      = 0.978, p < 0.001); thus with HL cells, both methods are usable. However, in
      macrophage cultures, the correlation was weaker (r = 0.133, p = 0.036) and we
      recommend PCR quantification for exact measurements.

PMID- 20041871
TI  - Phosphatase inhibitors with anti-angiogenic effect in vitro.
AB  - Levamisole has previously been identified as an inhibitor of angiogenesis in
      vitro and in vivo, but the mechanism behind the anti-angiogenic behavior has not
      yet been established. However, one known effect of levamisole is the inhibition
      of alkaline phosphatase, and this fact encouraged us to test other phosphatase
      inhibitors for their anti-angiogenic effects by using the same method as used to
      identify levamisole: an ELISA-based co-culture angiogenesis assay giving
      quantitative and qualitative results. Historically, intracellular phosphatases
      have been associated with the downregulation of signaling pathways, and kinases
      with their upregulation, but lately, the phospatases have also been coupled to
      positive signaling, which is why inhibition of phosphatases has become associated
      with anti-tumorigenic and anti-angiogenic effects. The results obtained in this
      work reveal several agents with anti-angiogenic potential and give a strong
      indication that phosphatase inhibition is linked to anti-angiogenic activity. An
      apparent disruption of endothelial tube formation was seen for seven of eight
      phosphatase inhibitors tested in the angiogenesis assay. By looking at the
      morphological results, it was seen that most of the inhibitors impaired
      proliferation and elongation of the endothelial cells, which still had a
      differentiated appearance. One inhibitor, PTP inhibitor IV, seemed to impair
      endothelial cell differentiation and induced the same morphology as when cells
      were treated with levamisole, although at a 200 times lower concentration than
      that of levamisole. Hence, our work points out compounds with a potential that
      may be of use in the search for new medical products for the treatment of
      malignant tumors, or other conditions where angiogenesis plays a central role.

PMID- 20041872
TI  - Comparison of methods of DNA extraction for real-time PCR in a model of pleural
      tuberculosis.
AB  - Molecular methods have been reported to have different sensitivities in the
      diagnosis of pleural tuberculosis and this may in part be caused by the use of
      different methods of DNA extraction. Our study compares nine DNA extraction
      systems in an experimental model of pleural tuberculosis. An inoculum of
      Mycobacterium tuberculosis was added to 23 pleural liquid samples with different
      characteristics. DNA was subsequently extracted using nine different methods
      (seven manual and two automatic) for analysis with real-time PCR. Only two
      methods were able to detect the presence of M. tuberculosis DNA in all the
      samples: extraction using columns (Qiagen) and automated extraction with the TNAI
      system (Roche). The automatic method is more expensive, but requires less time.
      Almost all the false negatives were because of the difficulty involved in
      extracting M. tuberculosis DNA, as in general, all the methods studied are
      capable of eliminating inhibitory substances that block the amplification
      reaction. The method of M. tuberculosis DNA extraction used affects the results
      of the diagnosis of pleural tuberculosis by molecular methods. DNA extraction
      systems that have been shown to be effective in pleural liquid should be used.

PMID- 20041873
TI  - Vancomycin-resistant Enterococcus spp.: validation of susceptibility testing and
      in vitro activity of vancomycin, linezolid, tigecycline and daptomycin.
AB  - Vancomycin-resistant enterococci (VRE) have emerged to become a significant
      nosocomial pathogen. However, detection may be challenging and treatment
      possibilities are limited. Reports of resistance to linezolide, daptomycin and
      tigecycline underline the need for reliable susceptibility testing with respect
      to these compounds. We evaluated the in vitro activity of vancomycin, linezolid,
      daptomycin and tigecycline against a panel of VRE and vancomycin-susceptible
      enterococci by broth microdilution (BMD). Etest for determination of minimum
      inhibitory concentration of these four antibiotics and two disc diffusion assays
      for detecting VRE and for susceptibility testing against tigecycline and
      linezolid were evaluated. Before susceptibility testing, all isolates were
      classified by polymerase chain reaction as vanA or vanB gene positive or vanA/B
      gene negative. Linezolid, daptomycin and tigecycline had excellent in vitro
      activity towards all isolates. For daptomycin and tigecycline, the overall
      agreement between BMD and Etest was suboptimal. For both disc diffusion assays,
      use of current break points was inadequate to detect vancomycin resistance for
      isolates carrying the vanB gene. Inspection of the inhibition zone for a diffuse
      edge, as recommended, accurately predicted presence of the vanB gene.

PMID- 20041874
TI  - A selective broth enrichment combined with real-time nuc-mecA-PCR in the
      exclusion of MRSA.
AB  - We analyzed the performance of a selective enrichment broth combined with Taqman
      based real-time duplex nuc-mecA-PCR to expedite the screening of methicillin
      resistant Staphylococcus aureus (MRSA). We found the broth to be able to select
      MRSA strains (oxacillin MIC range 4-256 microg/ml) from MSSA strains. A total of
      31 MRSA strains were found from 1250 clinical samples screened. The nuc-mecA-PCR
      was positive from all enrichment broths containing MRSA. From the remaining 1219
      samples negative for MRSA on culture/subculture, 138 samples were nuc+/mecA+ in
      PCR. The sensitivity of the test was 93.5%, specificity 88.6%, positive
      predictive value 17.3%, and negative predictive value 99.8% as compared to
      culture. Thus, with this method, the negative MRSA results can be reliably
      reported within 24-48 h from sampling. The method is a practical additional
      alternative to those already described for the same purpose.

PMID- 20041868
TI  - Beta-lactam antibiotics: from antibiosis to resistance and bacteriology.
AB  - This review focuses on the era of antibiosis that led to a better understanding
      of bacterial morphology, in particular the cell wall component peptidoglycan.
      This is an effort to take readers on a tour de force from the concept of
      antibiosis, to the serendipity of antibiotics, evolution of beta-lactam
      development, and the molecular biology of antibiotic resistance. These areas of
      research have culminated in a deeper understanding of microbiology, particularly
      in the area of bacterial cell wall synthesis and recycling. In spite of this
      knowledge, which has enabled design of new even more effective therapeutics to
      combat bacterial infection and has provided new research tools, antibiotic
      resistance remains a worldwide health care problem.

PMID- 20041875
TI  - Frameshift mutation of SIRT1 gene in gastric and colorectal carcinomas with
      microsatellite instability.

PMID- 20041876
TI  - Somatic mutations of EGFR, ERBB2, ERBB3 and ERBB4 in juxtamembrane activating
      domains are rare in non-small cell lung cancers.

PMID- 20041877
TI  - Variability and impact on design of bioequivalence studies.
AB  - In 2008, the European Agency for the Evaluation of Medicinal Products released a
      draft guidance on the investigation of bioequivalence for immediate release
      dosage forms with systemic action to replace the former guidance of a decade ago.
      Revisions of the regulatory guidance are based upon many questions over the past
      years and sometimes continuing scientific discussions on the use of the most
      suitable statistical analysis methods and study designs, particularly for drugs
      and drug products with high within-subject variability. Although high within
      subject variability is usually associated with a coefficient of variation of 30%
      or more, new approaches are available in the literature to allow a gradual
      increase and a levelling off of the bioequivalence limits to some maximum wider
      values (e.g. 75-133%), dependent on the increase in the within-subject
      variability. The two-way, cross-over single dose study measuring parent drug is
      still the design of first choice. A partial replicate design with repeating the
      reference product and scaling the bioequivalence for the reference variability
      are proposed for drugs with high within-subject variability. In case of high
      variability, more regulatory authorities may accept a two-stage or group
      sequential bioequivalence design using appropriately adjusted statistical
      analysis. This review also considers the mechanisms why drugs and drug products
      may exhibit large variability. The physiological complexity of the
      gastrointestinal tract and the interaction with the physicochemical properties of
      drug substances may contribute to the variation in plasma drug concentration-time
      profiles of drugs and drug products and to variability between and within
      subjects. A review of submitted bioequivalence studies at the Food and Drug
      Administration's Office of Generic Drugs over the period 2003-2005 indicated that
      extensive pre-systemic metabolism of the drug substance was the most important
      explanation for consistently high variability drugs, rather than a formulation
      factor. These scientific efforts are expected to further lead to revisions of
      earlier regulatory guidance in other regions as is the current situation in
      Europe.

PMID- 20041878
TI  - Different effects of scopolamine and inhibition of prolyl oligopeptidase on
      mnemonic and motility functions of young and 8- to 9-month-old rats in the radial
      arm maze.
AB  - Prolyl oligopeptidase (POP) has been connected to memory and mood through
      regulation of the brain levels of its biologically active peptide substrates and
      phosphatidylinositol system. This is the first study in a radial-arm maze of the
      effects of a single dose of a novel potent prolyl oligopeptidase inhibitor, KYP
      2047 (5 mg/kg, dissolved in 5% Tween 80), on memory and learning of scopolamine
      treated (0.4 mg/kg, dissolved in saline) rats. Habituated (days 1 and 2) and
      trained (days 3-11) young (3 months) and old (8-9 months) male Wistar rats were
      given (i) saline + Tween, (ii) saline + KYP-2047, (iii) scopolamine + Tween or
      (iv) scopolamine + KYP-2047 30 min. prior to testing their memory. Food rewards
      located in four randomly chosen arms of the maze. The rat had 10 min. to find and
      eat the rewards. Time spent in the maze, visits to each arm and number of eaten
      rewards were measured. Old rats made generally more errors, spent more time and
      visited fewer arms per minute in the maze than young rats. The memory- and
      function-impairing effects of scopolamine were also seen more clearly in old than
      young rats. KYP-2047 had no or only a marginal effect on memory of either age
      group, but when given without scopolamine, it slightly increased the maze
      motility of young rats and decreased the motility of old rats. In a separate
      locomotor activity test, KYP-2047 enhanced the motility of young rats supporting
      a suggested role of POP in motor functions.

PMID- 20041879
TI  - L-carnitine attenuates cardiac remodelling rather than vascular remodelling in
      deoxycorticosterone acetate-salt hypertensive rats.
AB  - L-carnitine is an important co-factor in fatty acid metabolism by mitochondria.
      This study has determined whether oral administration of L-carnitine prevents
      remodelling and the development of impaired cardiovascular function in
      deoxycorticosterone acetate (DOCA)-salt hypertensive rats (n = 6-12; #p < 0.05
      versus DOCA-salt). Uninephrectomized rats administered DOCA (25 mg every 4th day
      s.c.) and 1% NaCl in drinking water for 28 days developed cardiovascular
      remodelling shown as systolic hypertension, left ventricular hypertrophy,
      increased thoracic aortic and left ventricular wall thickness, increased left
      ventricular inflammatory cell infiltration together with increased interstitial
      collagen and increased passive diastolic stiffness and vascular dysfunction with
      increased plasma malondialdehyde concentrations. Treatment with L-carnitine (1.2%
      in food; 0.9 mg/g/day in DOCA-salt rats) decreased blood pressure (DOCA-salt 169
      +/- 2; + L-carnitine 148 +/- 6# mmHg), decreased left ventricular wet weights
      (DOCA-salt 3.02 +/- 0.07; + L-carnitine 2.72 +/- 0.06# mg/g body-wt), decreased
      inflammatory cells in the replacement fibrotic areas, reduced left ventricular
      interstitial collagen content (DOCA-salt 14.4 +/- 0.2; + L-carnitine 8.7 +/- 0.5#
      % area), reduced diastolic stiffness constant (DOCA-salt 26.9 +/- 0.5; + L
      carnitine 23.8 +/- 0.5# dimensionless) and decreased plasma malondialdehyde
      concentrations (DOCA-salt 26.9 +/- 0.8; + L-carnitine 21.2 +/- 0.4# micromol/l)
      without preventing endothelial dysfunction. L-carnitine attenuated the cardiac
      remodelling and improved cardiac function in DOCA-salt hypertension but produced
      minimal changes in aortic wall thickness and vascular function. This study
      suggests that the mitochondrial respiratory chain is a significant source of
      reactive oxygen species in the heart but less so in the vasculature in DOCA-salt
      rats, underlying the relatively selective cardiac responses to L-carnitine
      treatment.

PMID- 20041880
TI  - Induced DNA damage by dental resin monomers in somatic cells.
AB  - The present in vivo study investigated the genotoxicity of four dental resin
      monomers: triethyleneglycoldimethacrylate (TEGDMA), hydroxyethylmethacrylate
      (HEMA), urethanedimethacrylate (UDMA) and bisphenol A-glycidylmethacrylate
      (BisGMA). The Somatic Mutation and Recombination Test (SMART) in Drosophila
      melanogaster was applied to analyse their genotoxicity expressed as homologous
      mitotic recombination, point and chromosomal mutation. SMART detects the loss of
      heterozygosity of marker genes expressed phenotypically on the fly's wings. This
      fruit fly has an extensive genetic homology to mammalians, which makes it a
      suitable model organism for genotoxic investigations. The present findings
      provide evidence that the mechanistic basis underlying the genotoxicity of UDMA
      and TEGDMA is related to homologous recombination and gene/chromosomal mutation.
      A genotoxic pattern can correspondingly be discerned for both UDMA and TEGDMA:
      their genotoxicity is attributed respectively to 49% and 44% of mitotic
      recombination, as well as 51% and 56% of mutational events, including point and
      chromosomal alterations. The monomer UDMA is 1.6 times more active than TEGDMA to
      induce mutant clones per treatment unit. BisGMA and HEMA had no statistically
      significant effect on total spot frequencies - suggesting no genotoxic action in
      the SMART assay. The clinical significance of these observations has to be
      interpreted for data obtained in other bioassays.

PMID- 20041881
TI  - Evaluating the angina plan in patients admitted to hospital with angina: a
      randomized controlled trial.
AB  - The aim of this trial was to evaluate the Angina Plan (AP), a cognitive
      behavioral nurse-facilitated self-help intervention against standard care (SC). A
      randomized controlled trial of 218 patients hospitalized with angina assessed
      participants predischarge and 6 months later. Data were collected during a
      structured interview using validated questionnaires, self-report, and
      physiological measurement to assess between group changes in mood, knowledge and
      misconceptions, cardiovascular risk, symptoms, quality of life, and health
      service utilization. The intention-to-treat (ITT) analysis found no reliable
      effects on anxiety and depression at 6 months. AP participants reported increased
      knowledge, less misconceptions, reduced body mass index (BMI), an increase in
      self-reported exercise, less functional limitation, and improvements in general
      health perceptions and social and leisure activities compared to those receiving
      SC. Sensitivity analysis excluding participants with high baseline depression
      revealed a statistical significant reduction in depression levels in AP compared
      to the SC participants. Analysis excluding participants receiving cardiac surgery
      or angioplasty removed the ITT effects on physical limitation, self-reported
      exercise and general health perceptions and the improvements seen in social and
      leisure activities, while adaptive effects on knowledge, misconceptions and BMI
      remained and between-group changes in depression approached significance.
      Initiating the AP in a secondary care setting for patients with new and existing
      angina produces similar benefits to those reported in newly diagnosed primary
      care patients. Further evaluation is required to examine the extent of observed
      effects in the longer term. 

PMID- 20041882
TI  - Benefits and risks of maintaining normothermia during cardiopulmonary bypass in
      adult cardiac surgery: a systematic review.
AB  - Cardiopulmonary bypass is associated with significant morbidities, and the ideal
      temperature management during cardiopulmonary bypass remains uncertain. This
      review assessed the benefits and risks of maintaining normothermia during
      cardiopulmonary bypass in adult cardiac surgery. A total of 6,731 patients from
      44 randomized controlled trials in 14 countries, comparing normothermic (> 34
      degrees C) and hypothermic (<=34 degrees C) cardiopulmonary bypass in cardiac
      surgery (>18 years of age), were identified from MEDLINE (1966 to August 10,
      2009), EMBASE (1988 to August 10, 2009), and Cochrane controlled trials register
      and subject to meta-analysis. Two investigators examined all studies and
      extracted the data independently. Mortality after normothermic and hypothermic
      bypass was not significantly different (1.4% vs. 1.9% respectively, relative risk
      [RR] 1.38, 95% confidence interval [CI] 0.94-2.04, I(2) = 0%, P = 0.10).
      Hypothermic bypass was, however, associated with an increased risk of allogeneic
      red blood cells (RR 1.19, 95% CI 1.07-1.34, I(2) = 0%, P = 0.002), fresh frozen
      plasma (RR 1.54, 95% CI 1.06-2.24, I(2) = 7.7%, P = 0.02), and platelet
      transfusion (RR 2.53, 95% CI 1.26-5.06, I(2) = 44%, P = 0.009). The risk of
      stroke, cognitive decline, atrial fibrillation, use of inotropic support or intra
      aortic balloon pump, myocardial infarction, all-cause infections, and acute
      kidney injury after cardiac surgery was not significantly different between the
      two groups. The differences in the bypass time and targeted perfusion temperature
      were not significantly related to the risk of mortality and stroke. The current
      evidence suggests that maintaining normothermia during cardiopulmonary bypass in
      adult cardiac surgery is as safe as that of hypothermic surgery, and associated
      with a reduced risk of allogeneic blood transfusion.

PMID- 20041883
TI  - The other side of immunoglobulin G: suppressor of inflammation.
AB  - Immunoglobulin G (IgG) molecules can have two completely opposite functions. On
      one hand, they induce proinflammatory responses and recruit innate immune
      effector cells during infection with pathogenic microorganisms or autoimmune
      disease. On the other hand, intravenous infusion of high doses of pooled IgG
      molecules from thousands of donors [intravenous IG (IVIG) therapy] represents an
      efficient anti-inflammatory treatment for many autoimmune diseases. Whereas our
      understanding of the mechanism of the proinflammatory activity of IgG is quite
      advanced, we are only at the very beginning to comprehend how the anti
      inflammatory activity comes about and what cellular and molecular players are
      involved in this activity. This review will summarize our current knowledge and
      focus upon the two major models of either IVIG-mediated competition for IgG
      triggered effector functions or IVIG-mediated adjustment of cellular activation
      thresholds used to explain the mechanism of the anti-inflammatory activity.

PMID- 20041885
TI  - Clinical and genetic analysis of 18 pancreatic carcinoma/melanoma-prone families.
AB  - Families with both melanoma and pancreatic cancer are extremely rare and some are
      affected with the autosomal dominant inherited familial atypical multiple mole
      melanoma-pancreatic cancer (FAMMM-PC) syndrome. The phenotypic and genotypic
      expressions of such pancreatic cancer-melanoma prone families are not well
      defined. The National Case Collection of Familial Pancreatic Cancer of the
      Deutsche Krebshilfe includes 110 pancreatic cancer families, 18 of which (16%)
      show an association of pancreatic cancer and melanoma. These 18 families were
      analysed regarding their phenotype and the prevalence of germline mutations in
      the candidate genes CDKN2A, BRCA2, CHEK2, NOD2, ARL11 and Palladin (PALLD). There
      were two types of families: five families with the FAMMM-PC phenotype and 13
      PC/melanoma families without the multiple mole phenotypes (PCMS). The prevalences
      of PC and melanoma in the two types of families were similar. The prevalence of
      other tumour types, especially breast carcinoma, was higher (11%) in PCMS- than
      in FAMMM-PC families (2.4%, p = 0.02). CDKN2A mutations were identified in 2 of
      18 (11%) PCMS families. A cosegregating BRCA2 mutation was detected in one PCMS
      family without breast cancer. None of the reported germline mutations in the
      NOD2, Palladin, ARL11 or CHEK2 genes were detected in either type of family. In
      conclusion, families with an accumulation of PC and melanoma show a large variety
      of phenotypic expression, which is not always consistent with the FAMMM-PC
      phenotype. More PC/melanoma-prone families need to be analysed to clarify whether
      such families represent variations of the FAMMM-PC syndrome or two distinct
      hereditary cancer syndromes.

PMID- 20041884
TI  - Economic evaluation of immunoglobulin replacement in patients with primary
      antibody deficiencies.
AB  - Lifelong immunoglobulin replacement is the standard, expensive therapy for severe
      primary antibody deficiencies. This treatment can be administrated either by
      intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered
      at home or in an out-patient setting. This study aims to determine whether SCIG
      is cost-effective compared with IVIG from a French social insurance perspective.
      Because both methods of administration provide similar efficacies, a cost
      minimization analysis was performed. First, costs were calculated through a
      simulation testing different hypothesis on costs drivers. Secondly, costs were
      estimated on the basis of field data collected by a questionnaire completed by a
      population of patients suffering from agammaglobulinaemia and hyper
      immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented.
      Results of the simulation showed that direct medical costs ranged from 19 484
      euro for home-based IVIG to 25 583 euro for hospital-based IVIG, with home-based
      SCIG in between at 24 952 euro per year. Estimations made from field data were
      found to be different, with significantly higher costs for IVIG. This result was
      explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While
      the theoretical model showed very little difference between SCIG and hospital
      based IVIG costs, SCIG appears to be 25% less expensive with field data because
      of lower doses used in SCIG patients. The reality of the dose difference between
      both routes of administration needs to be confirmed by further and more specific
      studies.

PMID- 20041886
TI  - Overlapping syndrome with familial partial lipodystrophy, Dunnigan variety and
      cardiomyopathy due to amino-terminal heterozygous missense lamin A/C mutations.
AB  - Familial partial lipodystrophy, Dunnigan variety (FPLD) is a well-recognized
      autosomal dominant disorder due to heterozygous missense mutations in lamin A/C
      (LMNA) gene. Most of the FPLD patients harbor mutations in the C-terminal of the
      lamin A/C and do not develop cardiomyopathy. On the other hand, affected subjects
      from three FPLD pedigrees with heterozygous R28W, R60G and R62G LMNA mutations in
      the amino-terminal had associated cardiomyopathy presenting as premature onset of
      congestive heart failure, dilated cardiomyopathy and conduction system
      disturbances. We report three new FPLD pedigrees presenting with cardiomyopathy
      associated with heterozygous LMNA mutations in the amino-terminal region. Two of
      them had previously reported R60G and R62G mutations and one has a novel D192V
      mutation. Affected subjects belonging to the pedigree with heterozygous R62G
      mutation had atrial fibrillation and required pacemaker implantation. The
      affected subjects from the other pedigrees with R60G and D192V mutations
      developed severe cardiomyopathy requiring defibrillator implantation and cardiac
      transplantation before 30 years of age in some and premature death in the fourth
      decade in others. Thus, our report provides further evidence of association of a
      multisystem dystrophy syndrome in FPLD patients harboring amino-terminal
      mutations in LMNA. Increased understanding of the genotype-phenotype association
      might help devise clinical strategies aimed at preventing devastating
      manifestations of cardiomyopathy including heart failure, arrhythmias and sudden
      death. Furthermore, the underlying molecular mechanisms by which these amino
      terminal mutations cause lipodystrophy as well as cardiomyopathy remain to be
      understood.

PMID- 20041887
TI  - Comparison of fluorescence in situ hybridisation using peptide nucleic acid
      probes, Gram stain/acridine orange leukocyte cytospin and differential time to
      positivity methods for detection of catheter-related bloodstream infection in
      patients after haematopoietic stem cell transplantation.
AB  - In 46 febrile neutropenic patients who had undergone haematopoietic stem cell
      transplantation, the fluorescence in situ hybridisation using peptide nucleic
      acid probes (PNA FISH), Gram stain/acridine orange leukocyte cytospin
      (Gram/AOLC), and differential time to positivity (DTP) methods were performed for
      detection of catheter-related bloodstream infections (CRBSIs). As compared with
      the DTP method (which detected 11 patients with CRBSI), the PNA FISH and the
      Gram/AOLC methods detected ten of 11 CRBSI patients, resulting in a sensitivity,
      specificity, negative predictive value and positive predictive value of 91%,
      100%, 97% and 100%, respectively, for the PNA FISH method as well as for the
      Gram/AOLC method.

PMID- 20041890
TI  - Capnocytophaga species and preterm birth: case series and review of the
      literature.
AB  - Capnocytophaga, a genus of Gram-negative anaerobes that inhabit the oral cavity,
      has been reported to be an unusual cause of chorioamnionitis and neonatal
      infection. We report five cases of Capnocytophaga spp. infections in preterm
      infants (one proven infection and four probable infections) and review 14
      previously reported cases. We suggest that Capnocytophaga sp. may be responsible
      for some occult causes of chorioamnionitis or preterm birth, and that the
      prevalence of this infection may be higher than previously reported.

PMID- 20041891
TI  - Monitoring of nosocomial invasive aspergillosis and early evidence of an outbreak
      using cumulative sum tests (CUSUM).
AB  - In order to provide a statistically based evaluation of the incidence of invasive
      aspergillosis (IA) over time, we applied the cumulative sums (CUSUM) methodology,
      which was developed for quality control and has already been applied for the
      surveillance of hospital-acquired infections. Cases of IA were recorded during a
      5-year period. Incidence rates of cases assumed to be hospital-acquired, i.e.
      nosocomial IA (NIA), were analysed using CUSUM tests. Relationships between NIA,
      fungal contamination and construction or renovation work were tested using time
      series methods. Between January 2002 and December 2006, 81 cases of NIA were
      recorded. CUSUM analysis of NIA incidence showed no significant deviation from
      the expected monthly number of cases until August 2005, and then the CUSUM
      crossed the decision limit, i.e. identified a significant increase in NIA as
      compared with the reference period (January 2002 to December 2004). Up to April
      2006, the learning-curve CUSUM stayed over its limit, supporting an ongoing
      outbreak involving 24 patients, and then it significantly decreased in May 2006.
      Follow-up after May 2006 indicated no out-of-control situation, supporting a
      return to the baseline situation. In haematology wards, significant links were
      found between NIA incidence and fungal contamination of several sites at each
      ward (mainly unprotected common sites). An environmental source of contamination
      could be suspected, but no significant relationship was found between NIA
      incidence and ongoing construction or renovation. In conclusion, the CUSUM test
      proved to be well suited for real-time monitoring of NIA and for early
      identification and follow-up of an outbreak.

PMID- 20041892
TI  - Impact of immigration on tuberculosis in a low-incidence area of Italy: a
      molecular epidemiological approach.
AB  - The effects that immigration might have on the epidemiology of tuberculosis (TB)
      in a low-incidence area of Italy was investigated by determining, in
      autochthonous and immigrant TB patients, the molecular characteristics of the
      Mycobacterium tuberculosis complex (MTBC) isolates, which may provide information
      on their phylogeographical origin. A total of 1080 MTBC strains, collected during
      a 4- year period in Tuscany from 614 Italian-born and 466 foreign-born patients,
      were genotyped by spoligotyping and assigned to the different phylogeographical
      lineages that constitute the MTBC. The autochthonous Euro-American
      phylogeographical lineage, which includes the spoligotype families T, Haarlem,
      Latin American-Mediterranean (LAM), S and X, was highly prevalent among Italian
      born patients, with a total of 477 cases (77.7%), and foreign-born TB patients,
      with a total of 270 cases (57.9%); 24 Italian-born (3.9%) and 141 foreign- born
      (30.3%) TB cases were due to MTBC genotypic families associated with distant
      geographical areas, i.e. East African-Indian (EAI), Beijing, Central Asian (CAS),
      and Mycobacterium africanum. Strains of Mycobacterium bovis and strains of
      undefined genotype, which are all considered together, as it is not possible to
      assign a specific geographical origin, accounted for 113 (18.4%) Italian cases
      and 55 (11.8%) foreign-born cases. A total of 79 Italian TB cases (12.9%) have
      been attributed to transmission from immigrants to the local population. No
      significant contribution to drug resistance appeared to be associated with
      imported MTBC strains. It is concluded that, at present, the overall impact of
      imported TB on public health in the low-incidence study area is relatively modest
      and of the same order as in other western countries.

PMID- 20041893
TI  - Detection by microneutralization of antibodies against avian influenza virus in
      an endemic avian influenza region.
AB  - Detection by microneutralization of low-titre antibodies (anti-H5 micro-NT titre
      <= 1:80) against avian influenza virus (H5N1) is usually taken to be a false
      positive result. In this prospective study of 242 intensive-care unit patients
      admitted for severe community-acquired pneumonia, the prevalence of low-titre
      anti-H5 micro-NT was 2.4%. Prior exposure to poultry was the sole independent
      risk factor for these low-titre antibodies (adjusted OR 42.41; 95% CI 22.45
      64.51; p <0.001). We suggest that low anti-H5 micro-NT titres be interpreted in
      conjunction with plausible poultry, environmental and human exposure to H5N1.

PMID- 20041894
TI  - Impact of bacterial colonization on the severity, and accompanying airway
      inflammation, of virus-induced wheezing in children.
AB  - It is reported that bacterial colonization of the airway in neonates affects the
      likelihood and severity of subsequent wheezing in childhood. This study aimed to
      explore the impact of bacterial colonization on the severity of virus-induced
      wheezing, and accompanying airway inflammation. Nasopharyngeal aspirates (NPAs)
      from 68 hospitalized children with bronchiolitis and 85 children with recurrent
      wheezing were obtained. Eleven common respiratory viruses were sought by PCR
      and/or direct fluorescence assay. Bacteria were isolated from NPAs by routine
      culture methods. Cell numbers and concentrations of cytokines/chemokines in the
      NPAs were measured, and nucleated cells were characterized. The frequency of
      bacterial colonization in children with recurrent wheezing was significantly
      higher than in children with an initial attack of bronchiolitis. Bacterial
      colonization accompanying virus infection had no effect on clinical
      manifestations, duration of hospitalization, concentrations of
      cytokines/chemokines (except interleukin-10 (IL-10)) or cellularity in the
      children with bronchiolitis; however, among the children with recurrent wheezing,
      those who had coexistent non-invasive bacterial colonization and virus infection
      presented more frequent cyanosis, longer duration of hospitalization, a higher
      concentration of IL-10 and a higher percentage of neutrophils in NPAs than those
      with virus infection but without bacterial colonization. Bacterial colonization
      was common in children with virus-induced wheezing, particularly in the situation
      of recurrent wheezing. To some extent, bacterial colonization accompanying virus
      infection may contribute to the severity of the wheezing because of its impact on
      airway inflammation.

PMID- 20041895
TI  - Nosocomial outbreak of VIM-2 metallo-beta-lactamase-producing Pseudomonas
      aeruginosa associated with retrograde urography.
AB  - Pseudomonas aeruginosa is well adapted to the hospital setting and can cause a
      wide array of nosocomial infections that occasionally culminate in recalcitrant
      outbreaks. In the present study, we describe the first nosocomial outbreak of
      infection caused by bla(VIM-2)-positive P. aeruginosa in Germany. In November and
      December 2007, highly resistant P. aeruginosa isolates were recovered from the
      urine of 11 patients in the Department of Urology of a University Hospital.
      Bacterial isolates were typed by multilocus sequence typing and screened for
      known metallo-beta-lactamase (MBL) genes by PCR. Environmental sources of
      transmission were tested for bacterial contamination using surveillance cultures.
      Furthermore, a matched case-control study was performed in search of medical
      procedures significantly associated with case status. Typing of recovered
      isolates confirmed VIM-2 MBL-producing P. aeruginosa of sequence type 175 in all
      cases. Surveillance cultures did not lead to the identification of an
      environmental source of the outbreak strain. Case-control analysis revealed
      retrograde urography as the only exposure significantly associated with case
      status. The analyses suggest the transmission of a single clone of VIM-2 MBL
      producing P. aeruginosa leading to the infection of 11 patients within 47 days.
      Events in temporal proximity to retrograde urographies appear to have facilitated
      infection in the majority of cases. Department-specific infection control
      measures, including reinforced hygiene procedures during retrograde urography,
      quickly terminated the outbreak.

PMID- 20041896
TI  - High prevalence of mutators among Enterobacter cloacae nosocomial isolates and
      their association with antimicrobial resistance and repetitive detection.
AB  - We determined the mutation frequencies of 59 nosocomial isolates of Enterobacter
      cloacae, and investigated their association with antimicrobial susceptibility,
      genotype, and history of exposure to antimicrobials. The frequencies of mutations
      leading to rifampicin resistance ranged from 5.8 * 10(-9) to 8.0 * 10(-6)
      (median, 5.0 * 10(-8)). Seven of the 59 (12%) isolates were graded as strong
      mutators exhibiting a more than 50-fold increase in the mutation frequency
      relative to that of E. cloacae ATCC 13047, and 30 (52%) were graded as weak
      mutators exhibiting a more than five-fold and not more than 50-fold increase in
      the mutation frequency. The isolates with higher grade of mutation frequency were
      resistant to significantly more antimicrobials (medians of two, one and zero
      agents for strong mutators, weak mutators and non-mutators, respectively; p
      0.0078). The 59 isolates were classified into 36 genotypes, and all of the seven
      strong mutators had distinct genotypes. Mutation frequencies varied more than
      10(2)-fold within a clone. In patient-based, univariate analysis, intensive-care
      unit admission, dense antimicrobial exposure (glycopeptide or multiple classes)
      and repetitive detection of this species were significantly more common among all
      of the four patients from whom strong mutators were obtained. Strong mutators are
      highly prevalent in surgical isolates of E. cloacae. Higher mutation frequency
      was associated with antimicrobial resistance and repetitive detection, and may
      contribute to the adaptability of this species.

PMID- 20041897
TI  - Usefulness of simulated cases for assessing pandemic influenza preparedness
      plans.
AB  - To evaluate compliance with preparedness plans, actors simulating avian influenza
      attended various hospital emergency departments and public health centres during
      the last quarter of 2007. Most centres (89%) did not respond correctly. The
      useful information obtained was sent to the medical and administrative staff who
      were responsible for the preparedness plans. Awareness of these errors and their
      rectification can lead to improvements in the response to any case of influenza
      with pandemic potential and in the capacity to combat any other emergent or re
      emergent community infection.

PMID- 20041898
TI  - Pneumocystis jirovecii pneumonia in renal transplant recipients occurring after
      discontinuation of prophylaxis: a case-control study.
AB  - A case-control study was conducted to identify risk factors for Pneumocystis
      jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP
      were matched with 22 controls. Cases occurred a median of 18 months after
      transplantation, and none of the recipients was receiving prophylaxis. Univariate
      analysis showed that graft rejection, duration of steroid use, use of mammalian
      target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of
      prophylaxis discontinuation were risk factors for PCP. In the multivariate model,
      only graft rejection (OR 8.66, p 0.017) remained significantly associated with
      PCP. In patients with a history of graft rejection, PCP prophylaxis should be
      maintained, especially among those with lymphocytopenia.

PMID- 20041902
TI  - Microbiological investigation of a hospital outbreak of invasive group A
      streptococcal disease in Krakow, Poland.
AB  - The present study reports the epidemiological investigations undertaken in one of
      Krakow's city hospitals regarding the source of infection and the routes of
      transmission of a group A streptococcus (Streptococcus pyogenes), using
      fluorescent in situ hybridization as a rapid method for detecting S. pyogenes
      carriage in the medical personnel involved. Four patients from the gynaecology
      department and two patients from the surgery department presented with clinical
      signs of infection. Characteristics of the S. pyogenes strains isolated from
      patients and from one medical staff member, including the emm gene and
      superantigens encoding genes, are described. All patients (four confirmed and two
      probable cases) survived; the operating theatre aid was identified as an S.
      pyogenes carrier and the source of the infections.

PMID- 20041903
TI  - Secular trends and dynamics of hospital associated methicillin-resistant
      Staphylococcus aureus.
AB  - We performed an 11-year retrospective analysis of consecutive nonduplicate
      methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in two
      neighbouring hospitals in the Paris area. MRSA isolates were classified according
      to resistance (R) to fluoroquinolones (Fq), kanamycin (K), tobramycin (T) and
      gentamicin (G). The yearly number of MRSA isolates (3446 in total) decreased,
      from approximately 350 in 1997-2002 to 212 in 2007. Four patterns (P) were found:
      P1 (KTGFq R, n = 776), P2 [KTFq R; G susceptible (S), n = 1630], P3 (Fq R; KTG S,
      n = 397) and P4 (Fq S; any KTG susceptibility, n = 201). P1 predominated in 1997
      (183 isolates) then dropped sharply (nine in 2007); P2 and P4 remained stable
      over time; and P3 increased from 13 isolates in 1997 to 72 in 2007. Patterns were
      significantly and positively associated with several variables, independently of
      the year of collection: P1, age < 80 years, male gender, intensive care unit
      stay, and hospital onset; P3, age > 80 years and stay in intermediate or long
      term care wards; and P4, age < 40 years, stay in an obstetric ward, and imported
      cases. Molecular typing of 79 isolates in 2005 and 2007 using multilocus sequence
      typing, spa type, and SCCmec showed that P1, P2 and P3 isolates were mainly
      clonal, whereas P4 isolates were more diverse. P1 comprised mainly ST247-I
      isolates, P2 mainly ST8-IVc, and P3 mainly ST8-IVc and ST5-VI. In conclusion, the
      epidemiology of MRSA in Paris is changing rapidly at the local level, with
      phenotypically defined clones being substituted by others, with associations
      existing between changes in specific patient populations or circumstances.

PMID- 20041904
TI  - The search and destroy strategy prevents spread and long-term carriage of
      methicillin-resistant Staphylococcus aureus: results from the follow-up screening
      of a large ST22 (E-MRSA 15) outbreak in Denmark.
AB  - In the aftermath of a methicillin-resistant Staphylococcus aureus (MRSA) ST22
      hospital outbreak, we investigated the prevalence of long-term carriage, the
      efficacy of MRSA decolonization treatment (DT) and the spread of MRSA to
      households of patients and healthcare workers (HCWs). Furthermore, we evaluated
      the efficacy of repeated DT in long-term MRSA carriers. Of 250 index persons (58
      HCWs and 192 patients), 102 persons (19 HCWs and 83 patients) and 67 household
      members agreed to participate. Samples from all 169 persons were taken from the
      nose, throat, wounds and devices/catheters, and urine samples were additionally
      taken from index persons. Samples from companion animals (n = 35) were taken from
      the nostrils and anus. Environmental sites (n = 490) screened were telephone,
      television remote control, toilet flush handle, favourite chair and skirting
      board beside the bed. Sixteen (19%) patients and two household members, but no
      HCWs, were ST22-positive. The throat was the most frequent site of colonization.
      In a multivariate analysis, chronic disease (p <0.001) and pharyngeal carriage (p
      <0.001) were associated with long-term MRSA carriage. MRSA was found in the
      environments of four long-term carriers. All animals tested were negative. MRSA
      positive households were decolonized using nasal mupirocin TID and daily
      chlorhexidine body and hair wash for 5 days. Pharyngeal MRSA carriers also
      received fucidic acid (500 mg TID) combined with rifampicin (600 mg BID) or
      clindamycin (600 mg BID) for 7 days. The home environment was cleaned on days 2
      and 5. At the end of follow-up, ten of 16 long-term carriers and the two
      household contacts were MRSA-negative. In conclusion, decolonization of MRSA
      carriers is possible, but should include treatment of household members and the
      environment.

PMID- 20041905
TI  - Electromyographic tools to assess hemidiaphragm paralysis.
AB  - Non-invasive measurements of the phrenic nerve conduction time (CT) and
      diaphragmatic electromyographic response to voluntary inspiratory efforts may
      help to document an abnormal diaphragmatic function in the presence of
      hemidiaphragm elevation on chest radiographs. Twenty-one patients were addressed
      for the diagnosis of abnormal placement and motion of the right (13) or left (8)
      cupola on chest radiographs. CT was measured by recording the diaphragmatic M
      wave evoked by electrical transcutaneous phrenic nerve stimulation. The
      integrated diaphragmatic surface electromyogram (Edi) was recorded during sniff
      and Muller manoeuvres. Four patients were followed up during the next 8-16
      months. Among the twenty-one patients, five (24%) had a lengthened or absent CT.
      A right-to-left peak Edi asymmetry was measured in fourteen (67%), including
      those having abnormal CT. Agreement between side-related radiographic
      abnormalities and Edi asymmetry was high in the cases of an elevation of the
      right cupola (12/13, 92%) but poor when the left cupola was suspected (1/8, 13%).
      Long-term follow-up of Edi asymmetry showed a partial or total recovery. Thus,
      the combination of measurements of phrenic nerve CT and Edi recordings during
      voluntary inspiratory efforts confirmed 67% of the radiographic suspicion of
      diaphragmatic dysfunction.

PMID- 20041906
TI  - Human microvascular imaging: a review of skin and tongue videomicroscopy
      techniques and analysing variables.
AB  - Imaging techniques are increasingly important in clinical diagnostic work.
      Microcirculation is essential for function and survival of all tissues, but
      imaging techniques for microvascular monitoring of patients have only been used
      to a limited extent in clinical practice. The microcirculation is complex with
      its static and dynamic feature, and only skin and oral mucosa are readily
      accessible for microscopic examination. In addition, there is a no general
      agreement on which microvascular parameters and analysing techniques that could
      be useful. The aim of this article is to give an overview of techniques for human
      intra-vital microscopy and to describe software and variables used to analyse
      pictures and film sequences of human microcirculation. We also present clinical
      examples where microvascular examinations have been shown to be of diagnostic
      value. Improved techniques for assessing microvascular morphology and physiology
      will probably become important tools in clinical work in many disciplines in the
      near future.

PMID- 20041907
TI  - Image quality and myocardial scar size determined with magnetic resonance imaging
      in patients with permanent atrial fibrillation: a comparison of two imaging
      protocols.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of the heart generally requires
      breath holding and a regular rhythm. Single shot 2D steady-state free precession
      (SS_SSFP) is a fast sequence insensitive to arrhythmia as well as breath holding.
      Our purpose was to determine image quality, signal-to-noise (SNR) and contrast-to
      noise (CNR) ratios and infarct size with a fast single shot and a standard
      segmented MRI sequence in patients with permanent atrial fibrillation and chronic
      myocardial infarction. METHODS: Twenty patients with chronic myocardial
      infarction and ongoing atrial fibrillation were examined with inversion recovery
      SS_SSFP and segmented inversion recovery 2D fast gradient echo (IR_FGRE). Image
      quality was assessed in four categories: delineation of infarcted and non
      infarcted myocardium, occurrence of artefacts and overall image quality. SNR and
      CNR were calculated. Myocardial volume (ml) and infarct size, expressed as volume
      (ml) and extent (%), were calculated, and the methodological error was assessed.
      RESULTS: SS_SSFP had significantly better quality scores in all categories (P =
      0.037, P = 0.014, P = 0.021, P = 0.03). SNR(infarct) and SNR(blood) were
      significantly better for IR_FGRE than for SS_SSFP (P = 0.048, P = 0.018). No
      significant difference was found in SNR(myocardium) and CNR. The myocardial
      volume was significantly larger with SS_SSFP (170.7 versus 159.2 ml, P<0.001),
      but no significant difference was found in infarct volume and infarct extent.
      CONCLUSION: SS_SSFP displayed significantly better image quality than IR_FGRE.
      The infarct size and the error in its determination were equal for both
      sequences, and the examination time was shorter with SS_SSFP.

PMID- 20041908
TI  - The role of CYP3A5 genotypes in dose requirements of tacrolimus and everolimus
      after heart transplantation.
AB  - BACKGROUND: tacrolimus and everolimus are immunosuppressive drugs metabolized by
      enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3,
      results in strongly decreased CYP3A5 activity and has been shown to influence
      Tacrolimus blood concentrations, but its role for the pharmacogenetics of
      Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3
      variant in tacrolimus and everolimus dose and drug levels after heart
      transplantation. METHODS: The present study comprised 15 patients with Tacrolimus
      and 30 patients with Everolimus-based maintenance therapy after heart
      transplantation. CYP3A5 genotypes were determined and correlated with clinical
      data. RESULTS: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors
      (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average
      Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared
      to non-expressors. Tacrolimus levels were not significantly different at any
      point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors
      (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither
      Everolimus dose nor levels were significantly different between CYP3A5 expressors
      and non-expressors at any point of time. DISCUSSION: We conclude that in adult
      patients after heart transplantation, CYP3A5 genotypes have a strong influence on
      Tacrolimus, but not Everolimus dose requirement.

PMID- 20041909
TI  - Psychosocial evaluation of Chinese living related kidney donors.
AB  - BACKGROUND: Although living kidney transplantation has numerous advantages over
      cadaveric transplantation, donor apprehension remains a problem. This study
      investigated psychosocial features and quality of life in Chinese living kidney
      donors after transplantation procedures. METHODS: Participants were 84 donors
      interviewed during follow-up after donation. Sociodemographic characteristics
      were evaluated by a 22-item questionnaire. Social support, quality of life,
      depression, and anxiety were objectively measured with the Social Support Rating
      Scale for Chinese, the Short-Form 36 Health Survey, the modified Beck Depression
      Inventory, and the Self-Rating Anxiety Scale questionnaire, respectively.
      RESULTS: All donors volunteered without pressure from families or recipients.
      Altruistic motives were the main impetus for donation, and donors had good social
      support. Living transplantation affected donors' quality of life, with a slight
      negative effect on some physical aspects. There were no major depressive or
      anxiety disorders following donation. CONCLUSIONS: Living kidney donation was a
      generally positive experience without evidence of major psychological
      disturbance. However, considering the limited size and duration of our study, we
      recommend careful follow-up of all donors. We also recommend provision of social
      support services and removal of financial disincentives for donors.

PMID- 20041910
TI  - MR cholangiography in orthotopic liver transplantation: sensitivity and
      specificity in detecting biliary complications.
AB  - BACKGROUND: To assess the diagnostic value of magnetic resonance cholangiography
      (MRC) when evaluating biliary complications in a large series of liver
      transplants. METHODS: One hundred and twenty-nine patients prospectively
      underwent magnetic resonance (MR) imaging and MR cholangiography at 1.5-T device
      after orthotopic liver transplantation (OLT). After the preliminary acquisition
      of axial T1- and T2-weighted images, MRC involved respiratory-triggered, thin
      slab (2 mm), heavily T2-weighted fast spin-echo and breath-hold, thick-slab (10
      50 mm), single-shot T2-weighted sequences. MR images were blindly evaluated by
      two experienced readers in conference to determine the biliary anatomy and the
      presence of complications, whose final diagnosis was based on endoscopic
      retrograde cholangiography, percutaneous trans-hepatic cholangiography, and by
      integrating clinical follow-up with ultrasound and/or MR findings. RESULTS:
      Biliary complications were found in 60 patients (46.5%) and were represented by
      ischemic-type biliary lesions (n=21); anastomotic strictures (n=13); non
      anastomotic strictures (n=5); anastomotic strictures associated to lithiasis
      (n=6); lithiasis (n=6); papillary dysfunctions (n=9). The sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      reviewers for the detection of all types of biliary complications in patients
      with OLT were 98%, 94%, 94%, and 98%, respectively. CONCLUSIONS: MRC is a
      reliable technique for detecting post-OLT biliary complications and should be
      recommended before planning therapeutic interventions.

PMID- 20041911
TI  - A multicenter, placebo-controlled, double-blind, randomized study of efficacy and
      safety of ocinaplon (DOV 273,547) in generalized anxiety disorder.
AB  - Preclinical studies demonstrated that ocinaplon, a positive allosteric modulator
      of GABA(A) receptors, possesses anxiolytic-like actions at doses devoid of the
      side effects typically associated with benzodiazepines. The aim of this study was
      to evaluate the effects of ocinaplon in a multicenter, double-blind proof-of
      concept trial of male and female outpatients who met DSM-IV criteria for GAD with
      no coexisting depression, and had a baseline score of > or =20 on the Hamilton
      Scale for Anxiety (HAM-A). Patients with <20% reduction in HAM-A to placebo in a
      single-blind 7-day run-in period were randomly assigned to treatment with
      ocinaplon 90 mg t.i.d. (n = 31) or placebo for 28 days (n = 29). Ocinaplon was
      more effective than placebo in reducing HAM-A scores (P= 0.009). Patients
      assigned to ocinaplon exhibited a mean improvement of 14.2 points (SE = 2.6) on
      the total score of the HAM-A scale at the conclusion of the trial, while patients
      assigned to placebo obtained a mean improvement of 6.3 points (SE = 2.0). A
      significant (P= 0.023) difference in improvement between ocinaplon and placebo
      was observed beginning at and continuing from 1-week after the initiation of
      dosing. The proportion of patients with treatment-emergent adverse events (TEAE)
      was not statistically significant between ocinaplon and placebo. One serious
      adverse event (SAE) occurred in the ocinaplon group that was considered possibly
      related to study medication (icterus following transaminase elevations). The
      patient had preexisting medical conditions that may have contributed to this SAE.
      A full recovery was observed with no residual effects. The overall safety profile
      revealed no patterns of TEAEs, including those effects typically associated with
      other anxiolytic and/or benzodiazepine compounds, such as sedation. Ocinaplon
      appears to be a well-tolerated and effective treatment for GAD. It produces a
      rapid onset of anxiolytic action absent the side effects (e.g., dizziness,
      sedation) typically reported following anxiolytic doses of benzodiazepines.

PMID- 20041912
TI  - Age at death of patients with colorectal cancer and the effect of lead-time bias
      on survival in elective vs emergency surgery.
AB  - AIM: Colorectal cancer survival depends on stage at presentation, and current
      strategies aim for improvements through early detection. Previous studies have
      demonstrated improved survival from diagnosis but not increased life expectancy.
      While lead-time bias may account for variations in known prognostic indicators
      and also influence screening programmes, only age at death provides a true
      representation of the effectiveness of an intervention. We aimed to compare age
      at death for patients with colorectal cancer presenting on an emergency or
      elective basis. METHOD: Patients presenting with colorectal cancer (2000-2006)
      were entered into a prospective database (analysis 1 December 2008). Fields
      included age at death, emergency/elective presentation, palliative/curative
      intent and disease stage. RESULTS: One thousand six hundred and fifty patients
      (922 men) were identified. Elective patients presented younger than emergency
      patients (67.9 vs 70.6 years; P < 0.005). Dukes B patients presented older than
      Dukes D (P = 0.02). Mortality was 41% at time of analysis; no difference was seen
      in mean age at death between emergency and elective presentation (72.8 vs 72.0
      years; P = 0.379) or palliative and curative intent (72.0 vs 72.5 years; P =
      0.604). CONCLUSION: Colorectal cancer is common in a population where actuarial
      life expectancy is limited. Current colorectal cancer early detection strategies
      may improve cancer-specific survival by increasing lead-time bias but do not
      influence overall life expectancy.

PMID- 20041913
TI  - The 'straight to test' initiative reduces both diagnostic and treatment waiting
      times for colorectal cancer: outcomes after 2 years.
AB  - AIM: This study aimed to determine whether a 'straight to test'(STT) strategy for
      2-week wait (2 wk) referrals for suspected colorectal cancer (CRC) reduced the
      time to diagnosis and treatment for patients with CRC. METHOD: Consecutive 2-week
      referrals for suspected CRC over a period of 2 years from February 2007 were
      analysed. The times to the first diagnostic test and treatment and the cancers
      identified were analysed for those going to STT or the outpatient clinic.
      RESULTS: Of 662 patients having a 2 wk referral, 519 (78.4%) were suitable for
      the hospital colorectal telephone triage service, 121 (18.3%) patients went to
      STT and 502 (75.8%) were seen in the clinic. Of these 401 (79.8%) underwent
      diagnostic tests and 25 (6.2%) had CRC and in 12 (2.9%) patients other cancers
      were detected. In the STT group, 7 (5.8%) patients were diagnosed with CRC. The
      median time to first diagnostic test was 12 days (IQR 9-13) in the STT pathway,
      compared with 23 days (17-31) in those seen in the clinic (P < 0.0001). The
      median time to first treatment was 40 (32-48) days for those via STT, compared to
      46 (28-55) days for those seen in the clinic (P = 0.004). A total of 162 CRC were
      diagnosed during the study period of whom 34 (20.9%) were 2 wk referrals (5.1% of
      all suspected CRC 2 wk referrals), and 14 (2.1%) other cancers were detected via
      this pathway. CONCLUSION: STT speeds up the patient pathway by reducing the time
      to diagnosis and treatment for patients with CRC.

PMID- 20041914
TI  - Autofluorescence imaging colonoscopy for the detection of dysplastic lesions in
      ulcerative colitis: a pilot study.
AB  - AIM: Autofluorescence imaging (AFI) is a novel technology for endoscopy, which
      enhances neoplastic lesions of the gastrointestinal tract. The aim of this
      investigation was to examine whether AFI colonoscopy can identify dysplasia in
      ulcerative colitis. METHOD: We examined 48 patients with ulcerative colitis by
      AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding
      lesions under conventional colonoscopy were observed by AFI. Those target areas
      were classified into low AF and high AF according to the colour under AFI
      colonoscopy. The grade of dysplasia was determined in the specimens obtained from
      the target areas. RESULTS: About 126 sites (35 protruding lesions and 91 flat
      areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas
      and to be low in 84 areas. The positive rate of dysplasia was higher in
      protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive
      dysplasia was not statistically different between lesions determined to be low AF
      (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in
      protruding lesions was significantly higher in low AF than in high AF (45.0%vs
      13.3%, P = 0.043), while the value in flat lesions was not different between low
      AF and high AF (8.2%vs 0%, P = 0.3). CONCLUSIONS: Autofluorescence imaging
      colonoscopy seems to have a role for the detection of dysplaia in ulcerative
      colitis.

PMID- 20041915
TI  - Short-term complications of wide-lumen stapled anastomosis after ileocolic
      resection for Crohn's disease: who is at risk?
AB  - AIM: There is growing evidence that stapled anastomoses are similarly effective
      compared to hand-sewn anastomoses in Crohn's patients. This study was designed to
      assess safety and limitations of wide-lumen stapled ileocolic anastomoses.
      METHOD: All patients with ileocolic resections for Crohn's disease perfomed
      between 1998 and 2006 were studied. A stapled anastomosis was constructed
      whenever possible. Potential risk factors for postoperative complications were
      recorded, retrospectively. Univariate and multivariate analyses were performed.
      RESULTS: In 209 out of 220 cases (95%, 132 primary operations) stapled
      anastomoses were performed. Eleven patients underwent a hand-sewn anastomosis
      owing to massive bowel dilatation (n = 7) or increased wall thickness (n = 4).
      There were 10 major (4.5%; surgical: 8, medical: 2) complications including two
      anastomotic leaks and one anastomotic bleed (all from stapled anastomoses) and
      one death not related to the anastomosis. Minor complications occurred in 25
      patients. In multivariate analysis, major surgical postoperative complications
      were significantly associated with a low level of albumin (P = 0.0113) and
      previous resections for Crohn's disease (P = 0.0144). CONCLUSION: Stapled
      ileocolic anastomosis was safe in the majority of Crohn's patients. The most
      important limitation was technical impracticability. A low level of albumin and a
      history of previous resection increased the risk of postoperative complications.

PMID- 20041916
TI  - Interaction between synchronous bilateral prophylactic oophorectomy and adjuvant
      chemotherapy in female patients with locally advanced colorectal cancer.
AB  - AIM: In this study we explored the prognostic impact of synchronous bilateral
      prophylactic oophorectomy in female patients with primary colorectal cancer
      undergoing radical surgery. METHOD: From 1991 to 2000, 267 female patients with
      stage II or stage III colorectal cancer, who had undergone curative resection,
      were retrospectively reviewed. In 224 patients, the ovaries were preserved. The
      other 43 patients underwent synchronous bilateral prophylactic oophorectomy.
      Univariate and multivariate analyses (Kaplan-Meier and Cox regression,
      respectively) were used to evaluate the effect of prophylactic oophorectomy and
      other clinical factors on the prognosis of patients. RESULTS: Both univariate and
      multivariate analyses showed that tumor stage and adjuvant chemotherapy were the
      only two significant clinical factors that affected the 5-year overall survival
      of patients (P < 0.01). There was no significant difference in the 5-year overall
      survival between patients who had, or had not, undergone prophylactic
      oophorectomy (75%vs 73%, P > 0.05). In the subgroup analysis by adjuvant
      chemotherapy, the 5-year overall survival in patients receiving adjuvant
      chemotherapy was similar between nonoophorectomy and oophorectomy groups.
      However, in patients without adjuvant chemotherapy, the oophorectomy group was
      shown to have a significantly better 5-year overall survival than the
      nonoophorectomy group (76%vs 51%, P = 0.047). CONCLUSION: Prophylactic
      oophorectomy may improve the overall survival of female patients with locally
      advanced colorectal cancer without adjuvant chemotherapy, but its survival
      benefit vanished in patients receiving adjuvant chemotherapy. The role of
      prophylactic oophorectomy may be substituted by adjuvant chemotherapy, which
      makes prophylactic oophorectomy unnecessary during surgery for locally advanced
      colorectal cancer.

PMID- 20041917
TI  - Minimal anatomical disruption in stoma formation: the lateral rectus abdominis
      positioned stoma (LRAPS).
AB  - AIM: Parastomal hernias are difficult to manage and recent attention has focused
      on their prevention including the use of prophylactic mesh at the time of initial
      surgery. METHOD: A novel 'anatomical' approach to stoma formation, the lateral
      rectus abdominis positioned stoma (LRAPS), involving minimal anterior abdominal
      wall disruption is described. RESULTS: LRAPS was carried out electively (n = 25)
      or as an emergency (n = 4) for benign or malignant pathology. Twenty-two had a
      midline laparotomy and all types of stomas were fashioned. There were two early
      and three later deaths from advanced malignancy. No parastomal hernias have been
      detected at a mean follow-up of 13 (range 7-18) months and none detected by CT
      scanning in 20 of 24 patients with colorectal cancer at a mean follow-up of 14
      (range 10-18) months. CONCLUSION: LRAPS reduces the incidence of early stomal
      herniation.

PMID- 20041918
TI  - The colorectal MDT: how we do it at Leicester.

PMID- 20041919
TI  - Diaphragm disease and small bowel enteropathy due to nonsteroidal anti
      inflammatory drugs: a surgical perspective.

PMID- 20041920
TI  - The National Bowel Cancer Audit: the risks and benefits of moving to open
      reporting of clinical outcomes.
AB  - BACKGROUND: The government's proposals to openly report clinical outcomes poses
      challenges to the National Bowel Cancer Audit now funded by the UK department of
      health. AIM: To identify the benefits and risks of open reporting and to propose
      ways the risks might be minimized. METHODS: A review of the literature on
      clinical audit and the consequences of open reporting. RESULTS: There are
      significant potential benefits of a national audit of bowel cancer including
      protecting patients from sub-standard care, providing clinicians with externally
      validated evidence of their performance, outcome data for clinical governance and
      evidence that increases in government expenditure are achieving improvements in
      survival from bowel cancer. These benefits will only be achieved if the audit
      captures most of the cases of bowel cancer in the UK, the data collected is
      complete and accurate, the results are risk adjusted and these are presented to
      the public in a way that is fair, clear and understandable. Involvement of
      clinicians who have confidence in the results of the audit and who actively
      compare their own results against a national standard is essential. It is
      suggested that a staged move to open reporting should minimise the risk of
      falsely identifying an outlying unit. CONCLUSION: The fundamental aim of the
      National Bowel Cancer Audit is the pursuit of excellence by identification and
      adoption of best practice. This could achieve a continuous improvement in the
      care of all patients with bowel cancer in the UK. The ACPGBI suggests a safer way
      of transition to open reporting to avoid at least some of its pitfalls.

PMID- 20041921
TI  - Adult Hirschsprung's disease in Jamaica: operative treatment and outcome.
AB  - AIM: This study reviewed the operative management and outcome of patients with
      adult Hirschsprung's disease treated at the University Hospital of the West
      Indies, Mona, Jamaica. METHOD: The case notes for 11 patients with adult
      Hirschsprung's disease, treated operatively between January 1986 and December
      2007, were reviewed and data on preoperative diagnosis, operative procedures and
      postoperative complications were retrieved. RESULTS: Diagnosis was by open rectal
      biopsy in nine patients and by rectal suction biopsy in two patients. The time
      taken for preoperative bowel preparation ranged from 10 to 35 days, and colostomy
      was required in three patients to facilitate bowel cleansing. The Soave and
      Swenson procedures were used in six and five patients, respectively, leading to
      anastomotic stricture in one patient treated using the Soave procedure and to
      leakage in two patients treated using the Swenson procedure. All procedures took
      longer than 300 min, and 300-800 ml of blood or plasma was transfused.
      CONCLUSION: Therapeutic procedures for adult Hirschsprung's disease may result in
      life-threatening anastamotic complications. A protective colostomy is recommended
      when Swenson's procedure is used.

PMID- 20041922
TI  - E-learning vs lecture: which is the best approach to surgical teaching?
AB  - AIM: Most medical teaching is still delivered by traditional face-to-face
      interaction. E-learning has the potential benefit of instilling deeper learning
      of topics by virtue of repeated and convenient access to content presented in a
      range of media. We aimed to evaluate objectively the benefit of educating medical
      students on a common surgical topic (haemorrhoids), through a website and podcast
      package vs a traditional lecture. METHOD: Baseline knowledge was established by a
      questionnaire given to two different groups of third-year medical students
      starting their first clinical attachment. Group A (n = 73) was given a lecture
      and group B (n = 75) was asked to use a website containing text and pictures
      augmented by a podcast. Students were reassessed using the same preintervention
      questionnaire, and satisfaction was acquired from details given in a feedback
      form. RESULTS: There was no difference in knowledge between the two groups at
      baseline. Both groups demonstrated significant gains in knowledge after
      intervention (P < 0.0001). Group B (Web/podcast) showed a significantly greater
      increase in knowledge (P < 0.05) than group A (lecture). Preintervention
      subjective assessment of knowledge rated by the students showed no difference
      between the groups. Both groups of students were equally satisfied with the
      educational method. CONCLUSION: E-learning supplemented with a podcast results in
      greater knowledge acquisition when compared with a traditional lecture, without a
      loss of satisfaction with teaching. Using augmented Web-based educational tools
      reduces demands on teaching time with no decrease in quality for selected parts
      of the curriculum.

PMID- 20041923
TI  - Lower limb compartment syndrome following laparoscopic colorectal surgery: a
      review.
AB  - AIM:   In spite of recent advances in technology and technique, laparoscopic
      colorectal surgery is associated with increased operating times when compared
      with open surgery. This increases the risk of acute lower limb compartment
      syndrome. The aim of this review was to gain a better understanding of
      postoperative lower limb compartment syndrome following laparoscopic colorectal
      surgery and to suggest strategies to avoid its occurrence. METHOD: A MEDLINE
      search was performed using the keywords 'compartment syndrome', 'laparoscopic
      surgery' and 'Lloyd-Davies position' between 1970 and 2008. All relevant articles
      were retrieved and reviewed. RESULTS: A total of 54 articles were retrieved. Of
      the 30 articles in English, five were reviews, six were original articles and 19
      were case reports, of which only one was following laparoscopic colorectal
      surgery. The remaining 24 were non-English articles. Of these, two were reviews
      and 22 were case reports, of which only one was following laparoscopic colorectal
      surgery. The incidence of acute compartment syndrome following laparoscopic
      colorectal surgery is unknown. The following are believed to be risk factors for
      acute lower limb compartment syndrome: the Lloyd-Davies operating position with
      exaggerated Trendelenburg tilt, prolonged operative times and improper patient
      positioning. Simple strategies are suggested to reduce its occurrence.
      CONCLUSION: Simple preventative measures have been identified which may help to
      reduce the incidence of acute lower limb compartment syndrome. However, if
      suspected, timely surgical intervention with four-compartment fasciotomy remains
      the standard of care.

PMID- 20041924
TI  - Evidence-based colorectal surgery--facts, fiction or wishful thinking.

PMID- 20041925
TI  - Arterio-enteric fistula as a result of typhlitis.

PMID- 20041926
TI  - Management of the asymptomatic primary in the palliative treatment of metastatic
      colorectal cancer.

PMID- 20041927
TI  - Total perineal reconstruction after abdominoperineal excision for rectal cancer:
      long-term results of dynamic graciloplasty with Malone appendicostomy.
AB  - AIM: This study aimed to assess long-term function after total perineal
      reconstruction (TPR) with dynamic graciloplasty (DG) and systematic Malone
      appendicostomy (MA) adjunction after abdominoperineal excision (APR) for rectal
      cancer. METHOD: From 1999 to 2004, TPR using DG and MA was performed in 10
      patients [seven women; median age 40 (range 28-55) years] after APR for rectal
      cancer (cT2 in one patient, cT3 in six patients and cT4 in three patients). We
      prospectively recorded early and late morbidity, mortality, oncological outcome,
      functional results (using the modified Working Party on Anal Sphincter
      Replacement 'WPASR' scoring system) and quality of life (QoL; using the European
      Organisation for Research and Treatment of Cancer 'EORTC' QLQ-C30 and QLQ-CR38
      questionnaires). RESULTS: There was no procedure-related mortality. One patient
      required intra-abdominal re-operation. Nine patients required local and multiple
      revisions [there was one coloperineal anastomosis (CPA) stenosis, five CPA
      mucosal prolapse, three stenosis related to graciloplasty, two MA stenosis and
      one MA reflux]. After a median follow up of 78 months, there was no local
      recurrence and six patients were alive and disease-free. Regarding the functional
      results, the median modified WPASR score, of 8, after a follow up of 78 months,
      was good. The overall QoL scores remained stable over time. CONCLUSION: In
      carefully selected patients who want to avoid definitive abdominal colostomy
      after APR for rectal cancer, reconstruction involving MA and DG after APR for low
      rectal cancer is followed by good long-term function and QoL.

PMID- 20041928
TI  - Current management of locally recurrent rectal cancer.
AB  - AIM: A review of the literature was undertaken to provide an overview of the
      surgical management of locally recurrent rectal cancer (LRRC) after the
      introduction of total mesorectal excision (TME). METHOD: A systematic literature
      search was undertaken using PubMed, Embase, Web of Science and Cochrane
      databases. Only studies on patients having surgery for their primary tumour after
      1995, or if more than half of the patients were operated on after 1995, were
      considered for analysis. Studies concerning only palliative treatments were
      excluded. RESULTS: A total of 19 studies fulfilled the inclusion criteria.
      Locally recurrent rectal cancer still occurred in 5-10% of the patients and was a
      major clinical problem, due to severe symptoms and poor survival. In most
      studies, 40-50% of all patients with LRRC could be expected to undergo surgery
      with a curative intent and of those, 30-45% would have R0 resection. Thus, only
      20-30% of all patients with LRRC would have a potentially curative operation. The
      postoperative complication rate varied considerably, from 15 to 68%. The rate of
      re-recurrence varied from 4 to 54% after curative surgery. The 5-year overall
      survival varied between 9 and 39% and the median survival between 21 and 55
      months. CONCLUSION: Compared with previous studies, the proportion of potentially
      curative resections seems to have increased, probably due to improved staging,
      neoadjuvant treatment and increased surgical experience in dedicated centres,
      which has resulted in a tendency to improved survival.

PMID- 20041929
TI  - An open study of maintenance antibiotic therapy for chronic antibiotic-dependent
      pouchitis: efficacy, complications and outcome.
AB  - AIM: About 5% of restorative proctocolectomy (RPC) patients develop chronic
      antibiotic-dependent pouchitis. These require antibiotic maintenance therapy. We
      report our experience in managing this patient group. METHOD: Patients with RPC
      that was treated with antibiotic maintenance therapy were identified from the
      hospital pouch database. Data including faecal antibiotic sensitivity, functional
      outcome, side effects and Cleveland Global Quality of Life (CGQOL) score were
      recorded. RESULTS: Twenty-five patients were identified. The median length of
      treatment was 15.8 (range 3-62) months. Ten (40%) patients had pouchitis with co
      existing prepouch ileitis. The median frequency of defecation was 7 (range 4
      11)/24 h, the median clinical Pouch Disease Activity Index (PDAI) was 0 (range 0
      1) and the CQGOL score was 0.7 (range 0.5-1.0). Of those who relapsed, three
      (50%) patients had achieved mucosal healing following the induction of remission.
      Failure of mucosal healing did not predict a reduced time to relapse (P = 0.18).
      Prepouch ileitis was associated with an increased risk of developing antibiotic
      resistance (P = 0.023). Treatment of this with alternating antibiotic combination
      therapy was successful in all cases. CONCLUSION: Antibiotic maintenance therapy
      appears safe, well-tolerated and effective for the treatment of chronic
      antibiotic-dependent pouchitis. It results in an improved quality of life and
      function. Prepouch ileitis, but not failure of mucosal healing, is associated
      with an increased risk of developing antibiotic resistance.

PMID- 20041930
TI  - Quality of life after surgery for rectal cancer with special reference to pelvic
      floor dysfunction.
AB  - AIM: Conventional outcomes such as survival, tumour recurrence and complication
      rates after surgery for rectal cancer have been rigorously assessed, but the
      importance of maintaining quality of life (QOL) after surgery for rectal cancer
      has received less attention. The aim of the current study was to analyse QOL and
      the occurrence of pelvic dysfunction after the surgical treatment of rectal
      cancer. METHOD: Between May 2005 and May 2008, 150 patients with rectal cancer
      underwent abdominoperineal resection (APR) or anterior resection (AR). Seventy
      four answered two preoperative questionnaires. At a follow up of 1 year, 65 were
      alive without sign of recurrence and answered the same questionnaires: (a)
      validated RAND 36-item health survey QOL questionnaire; and (b) self-administered
      disease-related questionnaire with special reference to anorectal and urogenital
      function. RESULTS: The postoperative general QOL was similar after surgery, and
      mental functioning was better (P < 0.001). Problems with physical functions were
      associated with anal dysfunction after AR (P < 0.001) and problems with social
      functioning were associated with urinary dysfunction (P = 0.038). At 1 year after
      surgery, urinary incontinence was worse (P = 0.026) after all operations, and the
      incidence of dysuria was higher after APR than AR (P = 0.001). Male sexual
      function also worsened (P = 0.060). Anorectal dysfunction caused more
      inconvenience among patients who underwent AR (P = 0.028). Preoperative radiation
      was associated with postoperative ejaculation problems (P = 0.028) and anal
      incontinence (P = 0.012). CONCLUSION: Factors affecting QOL and pelvic floor
      function should be taken into account when making treatment decisions in rectal
      cancer.

PMID- 20041931
TI  - A meta-analysis of randomized controlled trials comparing antibacterial therapy
      with placebo in Crohn's disease.
AB  - AIM:  BACKGROUND: Antibacterial therapy has been investigated in several
      randomized, clinical trials compared with placebo for the management of Crohn's
      disease. Evidences for the efficacy of intervention are increasingly required.
      OBJECTIVES: To conduct a meta-analysis of randomized trials to compare the
      effects of antibacterial therapy versus placebo in patients with Crohn's disease.
      METHOD:  SEARCH STRATEGY: A systematic literature search of Pubmed, EMBASE,
      Cochrane Library (April 1966 to July 2009) was conducted using specific search
      terms. SELECTION CRITERIA: Eligible studies were randomized controlled trials
      comparing antibacterial (antimycobacterial and broad-spectrum antibiotic) therapy
      with placebo. DATA COLLECTION AND ANALYSIS: Studies were reviewed to determine
      the number of participants, mean follow-up, and the odds ratios (OR) for primary
      end point of clinical remission and clinical response were also abstracted. The
      meta-analysis was performed using a fixed-effects model or a randomized-effects
      model according to the degree of heterogeneity. RESULTS: Eleven randomized
      placebo-controlled clinical trials with 668 participants (364 patients in the
      treatment group and, 304 patients in the placebo group) were identified.
      Antimycobacterial agents were used in four of the trials and broad-spectrum
      antibiotics were used in the other seven trials. Pooled analysis showed no
      significant differences in the rates of clinical remission [OR = 1.28, 95%
      confidence interval (CI): 0.87-1.90, P = 0.214] and clinical response (OR = 1.52,
      95% CI: 0.91-2.55, P = 0.108) after receiving antibacterial treatment for 3
      months or longer. CONCLUSION: In this meta-analysis, no evidence of benefit for
      antibiotics in patients with Crohn's disease was found.

PMID- 20041932
TI  - Assessing patterns of participation and enjoyment in children with spinal cord
      injury.
AB  - AIM: To determine patterns of participation and levels of enjoyment in young
      people with spinal cord injuries (SCI) and to assess how informal and formal
      participation varies across child, injury-related, household, and community
      variables. METHOD: One hundred and ninety-four participants (106 males, 88
      females; mean age 13y 2mo, SD 3y 8mo, range 6-18y) with SCI and their primary
      caregivers completed a demographics questionnaire and a standardized measure of
      participation (the Children's Assessment of Participation and Enjoyment, [CAPE])
      at three pediatric SCI centers in a single hospital system in the United States.
      Their mean age at injury was 7 years 2 months (SD 5y 8mo, range 0-17y); 71% had
      paraplegia, and 58% had complete injuries. RESULTS: Young people participated
      more often in informal activities (t((174))=29.84, p<0.001) and reported higher
      enjoyment with these (t((174))=2.01, p=0.046). However, when engaging in formal
      activities, they participated with a more diverse group (t((174))=-16.26,
      p<0.001) and further from home (t((174))=-16.08, p<0.001). Aspects of informal
      participation were related to the child's age, sex, and injury level, and formal
      participation to the child's age and caregiver education. Caregiver education was
      more critical to formal participation among young people with tetraplegia than
      among those with paraplegia (F((4,151))=2.67, p=0.034). INTERPRETATION: Points of
      intervention include providing more participation opportunities for young people
      with tetraplegia and giving caregivers the resources necessary to enhance their
      children's formal participation.

PMID- 20041933
TI  - The predictive value of early neurological examination in neonatal hypoxic
      ischaemic encephalopathy and neurodevelopmental outcome at 24 months.
AB  - AIM: The clinical and electrographic signs of hypoxic-ischaemic encephalopathy
      (HIE) evolve over the first days of life. We examined the evolution of
      neurological signs over the first 3 days of life, and determined whether serial
      administration of the Amiel-Tison Neurological Assessment at Term (ATNAT) would
      predict neurodevelopmental outcome at 24 months. METHOD: Term (>37 wks'
      gestation) neonates born with suspected HIE between May 2003 and May 2005 in a
      Cork maternity unit were recruited prospectively. Modified Sarnat grading was
      assigned. The ATNAT was administered on days 1, 2, and 3 of life and a discharge
      neurological examination. Time to oral feeding and demographic variables were
      recorded. Developmental status was assessed using the revised Griffiths Mental
      Development Scales at 6, 12, and 24 months. RESULTS: Fifty-seven infants were
      recruited, with 51 (31 males, 20 females) included for follow-up. Neurological
      examination evolved and normalized over the first 3 days of life in many cases.
      At 24 months, 21 children had an adverse outcome, including six deaths.
      Examination at all time points correlated significantly with neurological outcome
      at 24 months. The best correlations were found to be (1) neurological examination
      at discharge (r=0.65, p<0.001), (2) Sarnat grading (r=0.64, p<0.001), and (3)
      ATNAT on day 3 (r=0.46, p<0.001). The best predictive value was seen with
      neurological examination at discharge (positive and negative predictive values of
      86% and 72% respectively). INTERPRETATION: Persistence of abnormal neurological
      signs correlates significantly with adverse outcome. The later a neonatal
      neurological examination was performed, the better its predictive ability.

PMID- 20041934
TI  - Severe childhood encephalopathy with dyskinesia and prolonged cognitive
      disturbances: evidence for anti-N-methyl-D-aspartate receptor encephalitis.
AB  - AIM: We report four cases of acquired severe encephalopathy with massive
      hyperkinesia, marked neurological and cognitive regression, sleep disturbance,
      prolonged mutism, and a remarkably delayed recovery (time to full recovery
      between 5 and 18mo) with an overall good outcome, and its association with anti-N
      methyl-d-aspartate (anti-NMDA) receptor antibodies. METHOD: We reviewed the four
      cases retrospectively and we also reviewed the literature. RESULTS: Anti-NMDA
      receptor antibodies (without ovarian teratoma detected so far) were found in the
      two children tested in this study. INTERPRETATION: The clinical features are
      similar to those first reported in 1992 by Sebire et al.,(1) and rarely
      recognized since. Sleep disturbance was not emphasized as part of the disorder,
      but appears to be an important feature, whereas coma is less certain and
      difficult to evaluate in this setting. The combination of symptoms, evolution
      (mainly seizures at onset), severity, paucity of abnormal laboratory findings,
      very slow recovery, and difficult management justify its recognition as a
      specific entity. The neuropathological substrate may be anatomically close to
      that involved in encephalitis lethargica, in which the same target functions
      (sleep and movement) are affected but in reverse, with hypersomnolence and
      bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis,
      which has been reported in adults and is often paraneoplastic.

PMID- 20041935
TI  - Functional taping: a promising technique for children with cerebral palsy.

PMID- 20041936
TI  - The transition between the phenotypes of Prader-Willi syndrome during infancy and
      early childhood.
AB  - AIM: Prader-Willi syndrome (PWS) is a genetic disorder historically characterized
      by two phenotypic stages. The early phenotype in infants is associated with
      hypotonia, poor suck, and failure to thrive. In later childhood, PWS is
      associated with intellectual disability, hyperphagia, as well as growth and sex
      hormone deficiency. Little is known about the transition between phenotypes. This
      study investigates the nature of the change in infancy and childhood PWS. METHOD:
      Forty-six children (22 females, 24 males; mean age 2 y 9 mo, SD 18.9 mo; range 7
      mo-5 y) with genetically confirmed PWS participated. Information was obtained on
      childhood height and weight, and eating behaviour from case notes and by parental
      interview. RESULTS: Weight standard deviation scores (SDS) started to exceed
      height by the end of the first year. Height SDS appeared to fall from near normal
      at birth until stabilizing below normal around 2 years. Half of the children
      whose body mass index (BMI) was higher than normal at interview had food
      interests greater than that of their peers, and the age at which increased age
      appropriate eating was first noted was later than the increase of BMI SDS.
      INTERPRETATION: Obesity may develop before the increased interest in food,
      suggesting underlying physiological factors independent of appetite control may
      be important.

PMID- 20041937
TI  - Obstetric brachial plexus palsy: a prospective, population-based study of
      incidence, recovery, and residual impairment at 18 months of age.
AB  - AIM: The aim of this investigation was to study the incidence of obstetric
      brachial plexus palsy (OBPP), to prospectively follow the recovery process, to
      assess the functional outcome at 18 months of age, and to find early prognostic
      indicators. METHOD: Of the 38 749 children born between 1999 and 2001 in western
      Sweden, 114 (70 males, 44 females) had an OBPP. Ninety-eight children were
      examined on six occasions at up to 18 months of age. Muscle strength, range of
      motion, hand preference, and functional abilities were noted, and the severity of
      the OBPP was classified. RESULTS: The incidence of OBPP was 2.9 per 1000 live
      births, and the incidence of persisting OBPP was 0.46 per 1000. At 3 months of
      age, the predictive value of regained elbow flexion for complete recovery was
      100%, 99% of shoulder external rotation, and 96% of forearm supination. Most of
      the 18 children with persisting OBPP could perform functional activities but
      asymmetries were noted. Five children had a mild, 11 had a moderate, and two had
      a severe impairment. Three had undergone nerve surgery, one with a mild and two
      with a severe persisting impairment. INTERPRETATION: Most children with an OBPP
      recover completely. Muscle strength at 3 months of age can be used to predict
      outcome.

PMID- 20041938
TI  - Ubiquity of Polynucleobacter necessarius ssp. asymbioticus in lentic freshwater
      habitats of a heterogeneous 2000 km area.
AB  - We present a survey on the distribution and habitat range of Polynucleobacter
      necessarius ssp. asymbioticus (PnecC), a numerically and functionally important
      taxon in the plankton of freshwater systems. We systematically sampled stagnant
      freshwater habitats in a heterogeneous 2000 km(2) area, together with
      ecologically different habitats outside this area. In total, 137 lakes, ponds and
      puddles were investigated, which represent an enormous diversity of habitats
      differing, e.g. in depth (< 10 cm-171 m) and pH (3.9-8.5). PnecC bacteria were
      detected by cultivation-independent methods in all investigated habitats, and
      their presence was confirmed by cultivation of strains from selected habitats
      representing the whole studied ecological range. The determined relative
      abundance of the subspecies ranged from values close to the detection limit of
      FISH (0.2%) to 67% (average 14.5%), and the highest observed absolute abundance
      was 5.3 x 10(6) cells ml(-1). Statistical analyses revealed that the abundance of
      PnecC bacteria was partially controlled by factors linked to concentrations of
      humic substances, which support the hypothesis that these bacteria utilize
      photodegradation products of humic substances. Based on the revealed statistical
      relationships, an average relative abundance of this subspecies of 20% in global
      freshwater habitats was extrapolated. Our study provides important implications
      for the current debate on ubiquity and biogeography in microorganisms.

PMID- 20041939
TI  - Infantile spasms and pigmentary mosaicism.
AB  - We present a 3-year-old boy with pigmentary mosaicism and persistent intractable
      infantile spasms due to mosaicism of chromosome 7. Getting the diagnosis of
      pigmentary mosaicism in a child with infantile spasms may not be easy, as most
      diagnostic work-up is done in infancy, at a time when skin manifestations can be
      subtle. We stress the need for a meticulous search for an etiology in cases of
      infantile spasms. Diagnostic work-up should include a dermatologic evaluation
      with skin biopsies for fibroblast culture (and karyotyping) from abnormal
      pigmented skin areas.

PMID- 20041941
TI  - High-density SNP screen of sodium channel genes by haplotype tagging and DNA
      pooling for association with idiopathic generalized epilepsy.
AB  - We have investigated seven voltage-gated sodium channel genes for association
      with idiopathic generalized epilepsy (IGE). Probands and control DNA were grouped
      into pools and used to screen 85 single-nucleotide polymorphisms (SNPs), mostly
      HapMap SNPs tagging the common variation in these genes. Twelve SNPs exhibiting
      an allele frequency difference between pools were genotyped individually in our
      sample of 232 probands, 313 controls, and 95 parent-proband trios. Two SNPs, in
      SCN1A and SCN8A, were associated by allele and genotype at nominal level of
      significance, but were not significant after Bonferroni correction. Two SCN2A
      SNPs (rs3943809 and rs16850331) were associated by case-control with a subgroup
      with IGE and history of febrile seizures and also by transmission disequilibrium
      test (TDT) in parent-proband trios. Both SNPs are part of a linkage
      disequilibrium (LD) cluster of 38 SNPs, but none are obvious functional variants.
      The association of rs3943809 with the febrile seizure subgroup (p = 0.0004)
      remains significant after the conservative Bonferroni correction for multiple
      testing.

PMID- 20041940
TI  - The natural history of epilepsy in tuberous sclerosis complex.
AB  - BACKGROUND: Although epilepsy affects most patients with tuberous sclerosis
      complex (TSC), little is known about the natural history of epilepsy in this
      genetic disease. METHODS: A retrospective chart review of all patients with TSC
      seen between January 2002 and October 2008. Charts were reviewed for a history of
      infantile spasms (IS), seizure other than IS, refractory epilepsy, Lennox-Gastaut
      syndrome (LGS), anticonvulsant medication use, ages of seizure onset, last
      seizure, last clinic visit, clinical seizure phenotype(s), cognitive impairment,
      and genetic mutation. RESULTS: Two hundred ninety-one patients were included.
      Among these patients, 37.8% had a history of IS; 85.2% had a history of seizure;
      54.1% developed multiple seizure types, not including IS; 63.2% had seizure onset
      in the first year of life; and 12.1% of adults without a seizure history
      developed epilepsy. Of epilepsy patients, 62.5% developed refractory epilepsy and
      33.5% achieved epilepsy remission; 37.5% of these patients achieved medication
      freedom. IS was a risk factor for refractory epilepsy (p<0.0001) and LGS
      (p<0.0001). History of seizure, IS, age at seizure onset, and refractory epilepsy
      each correlated with poor cognitive outcome (p<0.0001). Epilepsy remission
      correlated with better cognitive outcome (p<0.0001). TSC2 was a risk factor for
      IS and epilepsy; patients without an identified mutation were more likely to
      achieve remission. CONCLUSION: Most patients with TSC develop epilepsy and most
      develop multiple seizure types. Onset typically occurs in the first year of life;
      however, adults remain at risk. Although refractory epilepsy is common, many
      patients achieve seizure control. Many features of seizure history are predictive
      of cognitive and epilepsy outcome.

PMID- 20041942
TI  - Successful antiepileptic drug withdrawal in infants with epilepsy and
      cytomegalovirus neuroinfection: longitudinal study.
AB  - PURPOSE: A prospective study estimating antiepileptic and antiviral regimens
      administered to infants with symptomatic epilepsy and human cytomegalovirus
      (HCMV) neuroinfection followed for at least 4 years. METHODS: Thirty-two infants
      (19 female, 13 male) with epileptic seizures and HCMV neuroinfection diagnosed
      during the first year of life. Detection of HCMV DNA by qualitative polymerase
      chain reaction (PCR) method in cerebrospinal fluid (CSF), blood leukocytes, and
      urine confirmed the diagnosis. Infants were treated with intravenous ganciclovir
      (GCV) and different antiepileptic drugs. All had multiple electroencephalographic
      and neuroimaging examinations. Outcome of seizures was assessed using Engel
      classification system in the child's fourth year of life. RESULTS: Cessation of
      seizures was achieved in 19 infants (59.4%). In 11 children (34.4%) it was
      possible to withdraw administration of AEDs after 30-36 months. No infantile
      spasms, generalized tonic-clonic seizures, or polymorphic seizures were observed.
      They remained seizure-free for 1-6 years without relapse and their psychomotor
      development was normal. Four patients with intractable epilepsy (class V) had the
      longest GCV treatment (median 8 weeks). GCV treatment was implemented at the time
      or within 1 month after the onset of epileptic seizures in 10 of 11 infants
      withdrawn from AEDs. CONCLUSION: Early introduction of antiepileptic and
      antiviral GCV regimens in epilepsy and CMV neuroinfection may result in
      discontinuation of antiepileptic treatment and normal psychomotor development in
      infants.

PMID- 20041943
TI  - A long-term follow-up study of Dravet syndrome up to adulthood.
AB  - PURPOSE: We intended to elucidate the whole clinical course of Dravet syndrome
      (DS) comprehensively, from infancy through adulthood. METHODS: Subjects were 31
      patients with DS (14 with typical DS, and 17 with borderline DS) who were
      followed from childhood to at least 18 years of age. Their seizures, abilities,
      and electroencephalography (EEG) findings were investigated and statistically
      analyzed. RESULTS: The clinical findings of the patients with typical DS and
      those with borderline DS became largely similar in adolescence and adulthood.
      Seizures were intractable in childhood in all patients, but suppressed in five
      (16.1%) during follow-up. Thirty-five (87.5%) of the 40 apparently generalized
      convulsive seizures that were captured by ictal EEG recording at 7 years of age
      or later were of focal origin. The seizure-free outcomes were significantly
      correlated with the experience of <3 episodes of convulsive status epilepticus,
      and also with disappearance of spikes on the follow-up EEGs. Mental outcomes
      involving less severe intellectual disability were correlated with the presence
      of occipital alpha rhythms in the background activity of the follow-up EEGs. Mean
      age at the recording of the follow-up EEGs was 23.8 years. DISCUSSION: Prevention
      of the occurrence of convulsive status epilepticus was indicated to be critically
      important for the improvement of seizure prognosis in DS.

PMID- 20041944
TI  - Prevalence of interictal psychiatric disorders in patients with refractory
      temporal and extratemporal lobe epilepsy in Spain. A comparative study.
AB  - We aim to investigate whether temporal origin of epilepsy increases the risk of
      developing a psychiatric disorder and more specifically a major depressive
      disorder. The lack of standardized diagnostic instruments and the methodologic
      differences between studies highlight the fact that this issue warrants further,
      systematic, study. Three-hundred eight patients with complex partial seizures
      were classified according to temporal or extratemporal origin, following the
      Commission on Classification and Terminology of the International League Against
      Epilepsy (ILAE), 1989 localization-related concept. All patients were assessed
      using the Structured Interview for DSM-IV axis I psychiatric disorders (SCID-I).
      Lifetime and previous-year prevalence of psychiatric disorders were compared in
      temporal and extratemporal subgroups, using multivariate analysis. Previous-year
      major depression was significantly associated with temporal lobe origin. Our
      results do not support the hypothesis that patients with temporal lobe epilepsy
      (TLE) have more psychiatric illness in general, although they do suggest a
      specific connection between TLE and major depression.

PMID- 20041945
TI  - Intravenous lacosamide as short-term replacement for oral lacosamide in partial
      onset seizures.
AB  - PURPOSE: Lacosamide is a new antiepileptic drug effective for adjunctive
      treatment of partial-onset seizures. We evaluated the safety and tolerability of
      an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10,
      15, and 30 min as short-term replacement for oral lacosamide in patients with
      partial-onset seizures. METHODS: This multicenter, open-label, inpatient trial
      enrolled 160 patients from ongoing open-label, long-term trials who were taking
      stable doses of oral lacosamide and up to three concomitant antiepileptic drugs
      (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment
      to the same intravenous doses infused over progressively shorter infusion
      durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC)
      reviewed safety data for each cohort. The safety of intravenous lacosamide was
      assessed from adverse events (AEs), laboratory variables, electrocardiography
      findings, and physical/neurologic examinations. RESULTS: A total of 160 patients
      received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400
      800 mg/day doses. The most common AEs (reported by <or=10% of patients) were
      headache, dizziness, and somnolence. There was no increase in frequency or
      severity of AEs with shorter durations of infusion or increased days of exposure.
      AEs were similar, but more frequent, with higher doses (>or=400 mg/day).
      Injection-site events were rare and did not appear to be linked to infusion doses
      or rates. Lacosamide plasma concentrations were linearly related to dose across
      the cohorts. DISCUSSION: This comprehensive evaluation supports the safety of an
      intravenous lacosamide infusion duration as short as 15 min for short-term (2-5
      days) replacement for patients temporarily unable to take oral lacosamide.

PMID- 20041946
TI  - What changes in health-related quality of life matter to multiple myeloma
      patients? A prospective study.
AB  - OBJECTIVE: To determine the clinical significance of changes in quality-of-life
      scores in patients with multiple myeloma (MM), we have estimated the minimal
      important difference (MID) for the health-related quality-of-life instrument, the
      European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The
      MID is the smallest change in a quality-of-life score considered important to
      patients. METHODS: Between 2006 and 2008, 239 patients with MM completed the
      EORTC QLQ-C30 at inclusion (T1) and after 3 months (T2). At T2, a structured
      quality-of-life interview was also performed. MIDs were calculated by using mean
      score changes (T2-T1) for patients who in the interview stated they had improved,
      deteriorated or were unchanged. MIDs were also estimated by the receiver
      operating characteristic (ROC) curve method as well as by calculation effect
      sizes using standard deviations of baseline scores. RESULTS: MIDs varied slightly
      depending on the method used. Patients stating in the interview that they had
      'improved' or 'deteriorated' had a corresponding change in EORTC QLQ-C30 score
      ranging from 6 to15 (improvement) and from 9 to17 (deterioration) (scale range 0
      100). The ROC analysis indicated that changes in score from 7 to17 represent
      clinically important changes to patients. The effect size method suggested 5-6 to
      be a small and 11-15 to be a medium change. CONCLUSION: Calculation of MIDs as
      mean score changes or by ROC analysis suggested that a change in the EORTC QLQ
      C30 score in the range of approximately 6-17 is considered important by patients
      with MM. These MIDs are closer to a medium effect size than to a small effect
      size. Our findings imply that mean score changes smaller than 6 are unlikely to
      be important to the patients, even if these changes are statistically
      significant.

PMID- 20041948
TI  - Plasmodial heat shock proteins: targets for chemotherapy.
AB  - Heat shock proteins act as molecular chaperones, facilitating protein folding in
      cells of living organisms. Their role is particularly important in parasites
      because environmental changes associated with their life cycles place a strain on
      protein homoeostasis. Not surprisingly, some heat shock proteins are essential
      for the survival of the most virulent malaria parasite, Plasmodium falciparum.
      This justifies the need for a greater understanding of the specific roles and
      regulation of malarial heat shock proteins. Furthermore, heat shock proteins play
      a major role during invasion of the host by the parasite and mediate in malaria
      pathogenesis. The identification and development of inhibitor compounds of heat
      shock proteins has recently attracted attention. This is important, given the
      fact that traditional antimalarial drugs are increasingly failing, as a
      consequence of parasite increasing drug resistance. Heat shock protein 90
      (Hsp90), Hsp70/Hsp40 partnerships and small heat shock proteins are major malaria
      drug targets. This review examines the structural and functional features of
      these proteins that render them ideal drug targets and the challenges of
      targeting these proteins towards malaria drug design. The major antimalarial
      compounds that have been used to inhibit heat shock proteins include the
      antibiotic, geldanamycin, deoxyspergualin and pyrimidinones. The proposed
      mechanisms of action of these molecules and the pathways they inhibit are
      discussed.

PMID- 20041947
TI  - A molecular map of chloroquine resistance in Mali.
AB  - Plasmodium falciparum chloroquine resistance (CQR) transporter point mutation
      (PfCRT 76T) is known to be the key determinant of CQR. Molecular detection of
      PfCRT 76T in field samples may be used for the surveillance of CQR in malaria
      endemic countries. The genotype-resistance index (GRI), which is obtained as the
      ratio of the prevalence of PfCRT 76T to the incidence of CQR in a clinical trial,
      was proposed as a simple and practical molecular-based addition to the tools
      currently available for monitoring CQR in the field. In order to validate the GRI
      model across populations, time, and resistance patterns, we compiled data from
      the literature and generated new data from 12 sites across Mali. We found a mean
      PfCRT 76T mutation prevalence of 84.5% (range 60.9-95.1%) across all sites. CQR
      rates predicted from the GRI model were extrapolated onto a map of Mali to show
      the patterns of resistance throughout the participating regions. We present a
      comprehensive map of CQR in Mali, which strongly supports recent changes in drug
      policy away from chloroquine.

PMID- 20041949
TI  - Characterization of nontypeable Haemophilus influenzae collected from respiratory
      infections and invasive disease cases in Manitoba, Canada.
AB  - With the introduction of the Haemophilus influenzae serotype b (Hib) vaccine,
      invasive Hib disease has decreased substantially, but nontypeable H. influenzae
      (NT Hi) disease appears to be increasing. In order to understand the origin of NT
      Hi strains and their relationship with serotypeable strains, we analysed 125 NT
      Hi isolates collected from individual patients with either invasive disease (70
      isolates) or respiratory tract infections (55 isolates). Serotype-specific and
      capsular transport genes were absent by PCR analysis, confirming their
      nonencapsulated status, which also suggested the NT Hi isolates were not
      encapsulated strains that shed their capsules. Multilocus sequence typing
      confirmed the NT Hi isolates did not have the same genetic background as
      serotypeable strains, including Hib. Despite the genetic heterogeneity found, two
      major genetic clusters were identified, both containing invasive and respiratory
      isolates. Fourteen invasive isolates and nine respiratory isolates produced beta
      lactamase and were ampicillin resistant. More invasive (26.8%) than respiratory
      isolates (10.9%) showed decreased susceptibility towards ampicillin by a
      mechanism unrelated to beta-lactamase production. Besides a change in the capsule
      status of invasive Hi strains, the burden of invasive Hi disease, which used to
      be mainly a childhood disease, has now shifted to involve both adults and
      infants.

PMID- 20041950
TI  - Estimation of long-term bacterial respiration and growth efficiency in Lake
      Kinneret.
AB  - Semi-annual averaged values of photosynthetic carbon fixation (PCF), community
      respiration (CR), bacterial productivity (BP) and zooplankton carbon biomass,
      measured biweekly or monthly, were used to obtain long-term estimates of
      bacterial respiration (BR) and bacterial growth efficiency (BGE) in Lake Kinneret
      from 2001 through 2007. We posited that CR=BR+phytoplankton respiration
      (PR)+zooplankton respiration (ZR). Based on the results of independent
      experimental series, PR was estimated as 0.3 x gross primary production (GPP) and
      GPP as 1.5 x PCF. ZR was determined by multiplying zooplankton carbon biomass,
      measured biweekly, with published respiration rates for major zooplankton groups.
      From these data, we calculated BR and consequently BGE, determined as BP/(BR+BP).
      Over the entire study period, BR averaged 49 (+/-10)% of CR and was consistently
      higher during the first half of the year. Semi-annual averaged BGE ranged from
      26% to 53%, mean 39 (+/-9)%. Similar values of BGE were obtained if we did not
      use the measured values for ZR, but estimated BR+ZR from CR-PR and then assumed
      that BR ranged from two to three times ZR. The approach outlined in this paper
      can be useful for determining BGE in aquatic systems where long-term data sets of
      PCF, CR and BP are available.

PMID- 20041951
TI  - Spatial heterogeneity of dechlorinating bacteria and limiting factors for in situ
      trichloroethene dechlorination revealed by analyses of sediment cores from a
      polluted field site.
AB  - Microbiological analyses of sediment samples were conducted to explore potentials
      and limitations for bioremediation of field sites polluted with chlorinated
      ethenes. Intact sediment cores, collected by direct push probing from a 35-ha
      contaminated area, were analyzed in horizontal layers. Cultivation-independent
      PCR revealed Dehalococcoides to be the most abundant 16S rRNA gene phylotype with
      a suspected potential for reductive dechlorination of the major contaminant
      trichloroethene (TCE). In declining abundances, Desulfitobacterium,
      Desulfuromonas and Dehalobacter were also detected. In TCE-amended sediment
      slurry incubations, 66% of 121 sediment samples were dechlorinating, among them
      one-third completely and the rest incompletely (end product cis-1,2
      dichloroethene; cDCE). Both PCR and slurry analyses revealed highly heterogeneous
      horizontal and vertical distributions of the dechlorination potentials in the
      sediments. Complete reductive TCE dechlorination correlated with the presence of
      Dehalococcoides, accompanied by Acetobacterium and a relative of Trichococcus
      pasteurii. Sediment incubations under close to in situ conditions showed that a
      low TCE dechlorination activity could be stimulated by 7 mg L(-1) dissolved
      carbon for cDCE formation and by an additional 36 mg carbon (lactate) L(-1) for
      further dechlorination. The study demonstrates that the highly heterogeneous
      distribution of TCE degraders and their specific requirements for carbon and
      electrons are key issues for TCE degradation in contaminated sites.

PMID- 20041952
TI  - Microbial communities in streambed sediments recovering from desiccation.
AB  - Climate change affects running waters not only by increasing temperatures but
      also by increasing discharge variability as more frequent and severe floods and
      more frequent and longer droughts occur, especially in upper reaches.
      Mediterranean streams are known to experience droughts, but Central European
      headwaters are also beginning to be affected. The development of bacterial
      communities (abundance, composition) and the recovery of microbial functions
      (bacterial production, extracellular enzyme activity) were explored after
      rewetting desiccated streambed sediments via a sediment core perfusion technique.
      The bacterial community composition changed only slightly in the sediments from
      the Central European stream Breitenbach (Germany), but distinctly in the
      Mediterranean Mulargia River (Sardinia, Italy) during 4 days of experimental
      rewetting. Breitenbach sediments probably enabled survival of bacterial
      communities more similar to indigenous streambed communities, because they were
      less dry. High activity of enzymes involved in polymer degradation at the
      beginning of rewetting in both sediments indicated the persistence of
      extracellular enzymes during drought. After 4 days, nearly all microbial
      activities reached a level similar to unaffected sediments for the Breitenbach,
      but not for Mulargia. Here, much more intense drying resulted in a more distinct
      change and reduction of the microbial community, responsible for slower recovery
      of structure and functions.

PMID- 20041953
TI  - A single-nucleotide mutation in the -10 promoter region inactivates the narK2X
      promoter in Mycobacterium bovis and Mycobacterium bovis BCG and has an
      application in diagnosis.
AB  - Nitrate reduction is believed to be vital for the survival of tubercle bacteria
      under hypoxic/anaerobic conditions that are thought to prevail within granulomas.
      Nitrate reductase activity is rapidly induced in Mycobacterium tuberculosis (M.
      tb) under hypoxic conditions and is attributed to the induced expression of the
      nitrate/nitrite transporter gene, narK2. By contrast, Mycobacterium bovis (M.
      bovis) and M. bovis BCG (BCG) do not support the hypoxic induction of either
      nitrate reductase activity or narK2. Here, we show that the induction defect in
      the narK2X operon in M. bovis and BCG is caused by a -6T/C single nucleotide
      polymorphism (SNP) in the -10 promoter element essential for narK2X promoter
      activity. Complementation of M. bovis with both narGHJI and narK2X genes from M.
      tb failed to restore nitrate reductase activity in M. bovis, suggesting the
      involvement of additional genes/regulatory mechanisms for nitrate reduction that
      are absent in M. bovis. The -6T/C promoter-linked SNP enabled clear
      differentiation of M. tb from the other members of the M. tb complex, including
      M. bovis, BCG, Mycobacterium africanum and Mycobacterium microti, through a PCR
      RFLP assay.

PMID- 20041954
TI  - Unexpected oligomeric structure of the FocA formate channel of Escherichia coli :
      a paradigm for the formate-nitrite transporter family of integral membrane
      proteins.
AB  - FocA is a predicted formate channel with a deduced mass of 31 kDa that catalyzes
      the bidirectional movement of formate across the cytoplasmic membrane of
      Escherichia coli and is the archetype of the formate-nitrite transporter (FNT)
      family. Overproduced FocA variants with either an N- or a C-terminal Strep-tag
      increased formate import into anaerobic E. coli cells as determined by the
      enhanced activity of a single-copy formate-dependent fdhF::lacZ fusion. Using
      anti-FocA antibodies, we could show that both FocA variants were integrated into
      the cytoplasmic membrane. Circular dichroism spectroscopy of purified FocA(Strep
      N) revealed a high alpha-helical content of 56% consistent with the predicted six
      transmembrane helices present in the protein. Analysis of the oligomeric state by
      blue-native polyacrylamide gel electrophoresis revealed FocA to have an
      unexpected pentameric quaternary structure. This study reports the first
      isolation of an FNT family member.

PMID- 20041955
TI  - Energy production genes sucB and ubiF are involved in persister survival and
      tolerance to multiple antibiotics and stresses in Escherichia coli.
AB  - Persisters are a small population of slowly growing or nongrowing bacteria that
      are phenotypically resistant to antibiotics, but the mechanisms involved are not
      well understood. The aim of this study is to determine new mechanisms underlying
      antibiotic-tolerant persisters. The Escherichia coli deletion mutant library was
      screened to identify mutants that had a defect in persister survival after
      exposure to ampicillin for 24 h or 5 days. The identified mutants and the parent
      strain were subjected to minimum inhibitory concentration (MIC) and minimum
      bactericidal tests and antibiotic or stress conditions in exposure assays. sucB
      and ubiF mutants deficient in energy production were identified from the mutant
      screens to have defective persister survival as demonstrated by higher
      susceptibility to various antibiotics, including ampicillin, norfloxacin,
      tetracycline and gentamicin, and different stresses such as oxidative stress,
      acid pH and weak acid compared with the parent strain. In addition, both sucB and
      ubiF had a twofold lower MIC than the parent strain. The above sucB and ubiF
      mutant phenotypes could be complemented by their respective functional genes.
      Defective energy production through mutations in sucB and ubiF affects persister
      survival and could serve as new drug targets for persister bacteria.

PMID- 20041956
TI  - Lack of association between schizophrenia and polymorphisms in dopamine
      metabolism and transport genes.
AB  - We investigated the relationship between several functional polymorphisms in
      genes coding for dopamine metabolism and transport enzymes (MAO-A VNTR; MAO-A
      941T>G; DAT VNTR; DAT -67A/T; CYP2D6*3; CYP2D6*4; CYP2D6*5; CYP2D6*6) and the
      frequency of schizophrenia. Participants in the study were 242 subjects diagnosed
      with schizophrenia and related disorders and 290 hospital-based controls. Genomic
      DNA was isolated from whole blood and genotyped by several methods. However,
      there was no association between schizophrenia and the alleles, genotypes or
      diplotypes that were studied or their interactions. Polymorphisms in genes coding
      for dopamine metabolism and transport enzymes did not predispose to or protect
      from schizophrenia and related disorders.

PMID- 20041957
TI  - An improved manufacturing process for Xyntha/ReFacto AF.
AB  - SUMMARY: ReFacto Antihemophilic Factor is a second-generation antihaemophilia A
      product manufactured using a process that includes therapeutic grade human serum
      albumin (HSA) in the cell culture medium, but is formulated without HSA as a
      stabilizer. Even though this second-generation antihaemophilia product has a good
      safety profile, a programme was implemented to eliminate all animal- and human
      derived raw materials from the production process, thus producing a third
      generation product. To that end, HSA has been removed from the master and working
      cell banks and from the culture medium. The hybridoma-derived monoclonal antibody
      formerly used in the purification process has been replaced by a chemically
      synthesized affinity peptide, and a virus-retaining filtration step has been
      added to enhance the clearance of large viruses, such as retroviruses. The
      purification process has been validated for the removal of a panel of model
      viruses and provides significant clearance of all viruses tested. Host cell- and
      process-derived impurity removal validations also were conducted, including host
      cell DNA and protein, in addition to the affinity peptide. Compared with the
      product manufactured according to the original process, these changes had no
      detectable effect on the structural integrity, stability or clinical efficacy of
      this antihaemophilia A product. The product produced by the improved
      manufacturing process is named Xyntha/ReFacto AF.

PMID- 20041958
TI  - How we treat: haematuria in adults with haemophilia.

PMID- 20041959
TI  - Controversies regarding the prophylactic management of adults with severe
      haemophilia A.

PMID- 20041960
TI  - The effects of nocturnal compared with conventional hemodialysis on mineral
      metabolism: A randomized-controlled trial.
AB  - Hyperphosphatemia is common among patients receiving dialysis and is associated
      with increased mortality. Nocturnal hemodialysis (NHD) is a long, slow dialytic
      modality that may improve hyperphosphatemia and disorders of mineral metabolism.
      We performed a randomized-controlled trial of NHD compared with conventional
      hemodialysis (CvHD); in this paper, we report detailed results of mineral
      metabolism outcomes. Prevalent patients were randomized to receive NHD 5 to 6
      nights per week for 6to 10 hours per night or to continue CvHD thrice weekly for
      6 months. Oral phosphate binders and vitamin D analogs were adjusted to maintain
      phosphate, calcium and parathyroid hormone (PTH) levels within recommended
      targets. Compared with CvHD patients, patients in the NHD group had a significant
      decrease in serum phosphate over the course of the study (0.49 mmol/L, 95%
      confidence interval 0.24-0.74; P=0.002) despite a significant reduction in the
      use of phosphate binders. Sixty-one percent of patients in the NHD group compared
      with 20% in the CvHD group had a decline in intact PTH (P=0.003). Nocturnal
      hemodialysis lowers serum phosphate, calcium-phosphate product and requirement
      for phosphate binders. The effects of NHD on PTH are variable. The impact of
      these changes on long-term cardiovascular and bone-related outcomes requires
      further investigation.

PMID- 20041961
TI  - Transcription profiling of eleven cytochrome P450s potentially involved in
      xenobiotic metabolism in the mosquito Aedes aegypti.
AB  - Transcription profiles of 11 Aedes aegypti P450 genes from CYP6 and CYP9
      subfamilies potentially involved in xenobiotic metabolism were investigated. Many
      genes were preferentially transcribed in tissues classically involved in
      xenobiotic metabolism including midgut and Malpighian tubules. Life-stage
      transcription profiling revealed important variations amongst larvae, pupae, and
      adult males and females. Exposure of mosquito larvae to sub-lethal doses of three
      xenobiotics induced the transcription of several genes with an induction peak
      after 48 to 72 h exposure. Several CYP genes were also induced by oxidative
      stress and one gene strongly responded to 20-hydroxyecdysone. Overall, this study
      revealed that these P450s show different transcription profiles according to
      xenobiotic exposures, life stages or sex. Their putative chemoprotective
      functions are discussed.

PMID- 20041962
TI  - Bombyx mori Ras proteins BmRas1, BmRas2 and BmRas3 are neither farnesylated nor
      palmitoylated but are geranylgeranylated.
AB  - The lipid modifications which occur on Bombyx mori Ras proteins BmRas1, BmRas2
      and BmRas3 were studied by metabolic labelling in an insect cell-free protein
      synthesis system and in a baculovirus expression system, using specific
      inhibitors of protein prenylation and protein palmitoylation. In addition, the
      subcellular localization of BmRas proteins was examined using EGFP fusion
      proteins of constitutively active forms of BmRas proteins transiently expressed
      in Sf9 cells. As a result, it was revealed that the three B. mori Ras proteins
      BmRas1, BmRas2 and BmRas3 are neither farnesylated nor palmitoylated but are
      geranylgeranylated for localization to the plasma membrane of insect cells. Thus,
      the mechanism of membrane binding of insect Ras proteins is quite different from
      that reported for mammalian Ras proteins.

PMID- 20041963
TI  - Potential role of CXCL10 in the induction of cell injury and mitochondrial
      dysfunction.
AB  - Chemokines have been known to play a critical role in pathogenesis of chronic
      pancreatitis and acinar cell death. However, the role played by one of the CXC
      chemokines: CXCL10 in regulation of acinar cell death has remained unexplored.
      Hence, this study was designed to assess the role of CXCL10 promoting apoptosis
      in ex vivo cultured acinar cells. Primary human pancreatic acinar cell cultures
      were established and exposed to varying doses of CXCL10 for different time
      intervals. Apoptotic induction was evaluated by both qualitative as well as
      quantitative analyses. Various mediators of apoptosis were also studied by
      Western blotting, membrane potential (Psim) and ATP depletion in acinar cells.
      Analysis of apoptosis via DNA ladder and cell death detection - ELISA
      demonstrated that CXCL10 induced 3.9-fold apoptosis when administrated at an
      optimal dose of 0.1 mug of recombinant CXCL10 for 8 h. Quantitative analysis
      using FACS and dual staining by PI-annexin showed increased apoptosis (48.98 and
      53.78% respectively). The involvement of upstream apoptotic regulators like pJNK,
      p38 and Bax was established on the basis of their increased expression of CXCL10.
      The change of Psim by 50% was observed in the presence of CXCL10 in treated
      acinar cells along with enhanced expression of Cytochrome C, apaf-1 and caspase
      9/3 activation. In addition, ATP depletion was also noticed in CXCL10 stimulated
      acinar cells. CXCL10 induces cell death in human cultured pancreatic cells
      leading to apoptosis and DNA fragmentation via CXCR3 signalling. These signalling
      mechanisms may play an important role in parenchymal cell loss and injury in
      pancreatitis.

PMID- 20041965
TI  - A quantitative study of lung dysfunction following haemorrhagic shock in rats.
AB  - Haemorrhagic shock occasionally causes an episode of lung dysfunction, the
      severity of which appears to correlate with fatal outcome. Our previous study
      indicated that proinflammatory cytokines, such as tumour necrosis factor (TNF)
      alpha and interleukin (IL)-1beta, played a key role in the development of lung
      dysfunction through recruitment of activated neutrophils by causing pulmonary
      endothelial cell damage. Here, we examined this issue quantitatively by grading
      four groups of severity of bleeding in rats. As the amount of bleeding increased,
      the expression of mRNA for TNF-alpha and IL-1beta in the lung tissue and the
      pulmonary serum levels of both cytokines increased progressively up to 5 h, and
      the frequency of activated neutrophils increased likewise. The lung dysfunction
      indices serum lactic dehydrogenase-3 isozyme (LDH-3), partial pressure of
      arterial oxygen (PaO(2)) and alveolar-arterial oxygen tension difference
      (AaDO(2)) in blood deteriorated as the amount of bleeding increased. The
      frequency of activated neutrophils in the lung correlated well with the LDH-3
      level 5 h after haemorrhagic shock. The present results demonstrate that the
      increase of proinflammatory cytokines and the recruitment of activated
      neutrophils into the lung following haemorrhagic shock are quantitatively related
      to progression of lung dysfunction as the amount of bleeding increases.

PMID- 20041964
TI  - Proliferation and apoptotic rates and increased frequency of p63-positive cells
      in the prostate acinar epithelium of alloxan-induced diabetic rats.
AB  - The effects of experimental type 1 diabetes were investigated in the acinar
      epithelium of rat ventral prostate, focusing on the rates of cell proliferation
      and the frequency of apoptosis and p63-positive cells. Type 1 diabetes was
      induced in adult male Wistar rats by a single alloxan administration (42 mg/kg
      b.w.) and its effects were analysed for 1 week and 3 months after the
      establishment of the disease. A group of diabetic rats was treated daily with 5
      IU of insulin during 1 week after diabetes had been diagnosed. Immunocytochemical
      methods for the localization of cell proliferation antigen (PCNA), androgen
      receptor (AR) and p63 protein were carried out, and apoptotic cells were
      identified by TUNEL essay. In diabetic rats, testosterone levels reduced
      drastically after 1 week and in a lower degree after 3 months. In short-term
      diabetic rats, cell proliferation decreased, and in medium-term, epithelial
      apoptotic rates increased. In both periods after the onset of diabetes, the
      frequency of p63-positive cells doubled. Insulin treatment was effective in
      preventing testosterone decrease, p63-positive cell increase and apoptotic rates,
      but did not interfere in cell proliferation. This investigation shows that, soon
      after diabetes onset, there are important modifications in cell proliferation
      within the acinar prostatic epithelium, and in longer term, there is a marked
      impact on kinetics of differentiation and cell death, which may initially be
      attributable to an androgenic fall, but is probably also because of other factors
      related to diabetes, as changes are considerably different from those resulting
      from castration.

PMID- 20041966
TI  - Disorders related with ageing in the gerbil female prostate (Skene's paraurethral
      glands).
AB  - The female organs, which are regulated by steroid hormones, are targets of
      studies especially those related to senescence. However, although the female
      prostate is an organ influenced by hormones and susceptible to lesions, there is
      still little information about its histopathology. Thus, given the
      morphophysiological similarity between the prostate in women and female gerbils,
      the present study aimed to identify the spontaneous histopathological changes in
      this rodent to provide contributions to the understanding of lesions that also
      affect the human female prostate. The structural, ultrastructural,
      immunohistochemical, morphometric-stereological and serological aspects, as well
      as the quantification of the incidence, multiplicity and percentage of acini
      affected by different lesions were analyzed. Benign prostate lesions including
      hyperplasia, prostatitis, microcalculi and calculi; preneoplastic lesions like
      dysplasias; premalignant lesions, such as high grade prostatic intraepithelial
      neoplasia as well as malignant ones, specifically adenocarcinoma, were identified
      in the adult gland, but they were intensified during senescence, which is
      possibly due to the imbalance among steroid hormone levels. Although clinical
      attention focuses on other urogenital organs, the real condition of the
      histopathological injuries in the human female prostate should be considered. A
      serious preventive work regarding the female prostate could be applied in the
      gynaecological context in order to monitor the gland and avoid possible
      disturbances to women's health and consequently provide better quality of life.

PMID- 20041967
TI  - Myelodysplastic syndrome in elderly patients: correlation of CBC with cytogenetic
      and FISH analysis.
AB  - Unexplained anemia in the elderly could represent myelodysplastic syndrome (MDS).
      We assessed the utility of using a fluorescence in situ hybridization (FISH)
      panel for common chromosomal abnormalities seen in MDS. A total of 101 elderly
      outpatients with anemia of unknown etiology were evaluated. Complete blood count,
      bone marrow biopsy, conventional cytogenetic analysis (CC), and FISH panel were
      reviewed. A total of 21 (21%) of the 101 patients had MDS. A combination of CC
      and FISH identified chromosomal abnormalities in 17 (81%) of the patients with
      MDS. The remaining 4 (19%) were diagnosed with MDS based solely on morphologic
      criteria. Except in two cases, FISH did not reveal abnormalities not already
      detected by CC. Furthermore, MDS patients infrequently had isolated anemia (14%)
      as opposed to those without MDS (75%). A MDS FISH panel is not more sensitive
      than CC in elderly outpatients with unexplained anemia. MDS is more likely if in
      addition to anemia, leukopenia and/or thrombocytopenia are also present.

PMID- 20041968
TI  - Under-filled blood collection tubes containing K2EDTA as anticoagulant are
      acceptable for automated complete blood counts, white blood cell differential,
      and reticulocyte count.
AB  - Current laboratory standards from Clinical Laboratory Standards Institute (CLSI)
      and manufacturer's (Becton Dickinson) data indicate that under-filling K(2)EDTA
      blood collection tubes can result in erroneous hematology values. To accommodate
      under-filled tubes and reduce collection volumes while optimizing our automation,
      we explored the acceptable limit of under-filled tubes for hematology values. We
      collected 8.0 ml of blood from 30 normal adult volunteers. Each donation was
      aliquoted in the following volumes: 4.0, 2.0, 1.0, 0.5 ml x 2. These samples were
      analyzed within 1 h of blood collection on Sysmex XE-2100 (Sysmex America Inc.,
      Mundelein, IL, USA) for complete blood count, reticulocyte, and white blood cell
      differentials. Results of the under-filled tubes were compared to those of the
      standard volume. The Deming regression analysis show excellent correlation for
      all parameters between each under-filled blood collection volume compared to a
      standard 4 ml volume. The Bland and Altman analysis shows good agreement between
      both 1.0 and 2.0 ml compared to a 4.0 ml volume. The 0.5 ml compared to a 4.0 ml
      volume, however, shows increased variation on many parameters. In addition all
      three collection volumes show negative bias compared to the standard volume for
      platelet count, but the difference is considered insignificant with a percent
      difference of 5.5%, 3.2%, and 1.5% for 0.5, 1.0, and 2.0 ml collection volume
      respectively. Finally for 0.5 ml collection volume we noticed a low level of
      false positive flagging rate for white blood cell. Acceptable complete blood
      count values of under-filled powdered K(2)EDTA tubes can be obtained with as
      little as 1.0 ml of blood.

PMID- 20041969
TI  - Altered expression of claudin family proteins in Alzheimer's disease and vascular
      dementia brains.
AB  - Claudins (Cls) are a multigene family of transmembrane proteins with different
      tissue distribution, which have an essential role in the formation and sealing
      capacity of tight junctions (TJs). At the level of the blood-brain barrier (BBB),
      TJs are the main molecular structures which separate the neuronal milieu from the
      circulatory space, by a restriction of the paracellular flow of water, ions and
      larger molecules into the brain. Different studies suggested recently significant
      BBB alterations in both vascular and degenerative dementia types. In a previous
      study we found in Alzheimer's disease (AD) and vascular dementia (VaD) brains an
      altered expression of occludin, a molecular partner of Cls in the TJs structure.
      Therefore in this study, using an immunohistochemical approach, we investigated
      the expression of Cl family proteins (Cl-2, Cl-5 and Cl-11) in frontal cortex of
      aged control, AD and VaD brains. To estimate the number of Cl-expressing cells,
      we applied a random systematic sampling and the unbiased optical fractionator
      method. We found selected neurons, astrocytes, oligodendrocytes and endothelial
      cells expressing Cl-2, Cl-5 and Cl-11 at detectable levels in all cases studied.
      We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl
      11 in both AD and VaD as compared to aged controls. The ratio of astrocytes
      expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to
      aged controls. The ratio of oligodendrocytes expressing Cl-11 was significantly
      higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly
      higher in VaD as compared to aged controls. Within the cerebral cortex, Cls were
      selectively expressed by pyramidal neurons, which are the ones responsible for
      cognitive processes and affected by AD pathology. Our findings suggest a new
      function of Cl family proteins which might be linked to response to cellular
      stress.

PMID- 20041970
TI  - Repair of senescent myocardium by mesenchymal stem cells is dependent on the age
      of donor mice.
AB  - Myocardial infarction is one of the leading causes of mortality in aged people.
      Whether age of donors of mesenchymal stem cells (MSCs) affects its ability to
      repair the senescent heart tissue is unknown. In the present study, MSCs from
      young (2 months) and aged (18 months) green fluorescent protein expressing
      C57BL/6 mice were characterized with p16(INK4a) and beta-gal associated
      senescence. Myocardial infarction was produced in 18-month-old wild-type C57BL/6
      mice transplanted with MSCs from young and aged animals in the border of the
      infarct region. Expression of p16(INK4a) in MSCs from aged animals was
      significantly higher (21.5%+/- 1.2, P < 0.05) as compared to those from young
      animals (9.2%+/- 2.8). A decline in the tube-forming ability on Matrigel was also
      observed in aged MSCs as well as down-regulation of insulin-like growth factor-1,
      fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and
      hepatocyte growth factor (HGF) compared to young cells. Mice transplanted with
      young MSCs exhibited significant improvement in their left ventricle (LV)
      systolic and diastolic function as demonstrated by dp/dt(max) , dp/dt(min) ,
      P(max) . Reduction in the LV fibrotic area was concomitant with
      neovascularization as demonstrated by CD31 and smooth muscle actin (SMA)
      expression. Real-time RT-PCR analysis for VEGF, stromal cell derived factor (SDF
      1alpha) and GATA binding factor 4 (GATA-4) genes further confirmed the effect of
      age on MSC differentiation towards cardiac lineages and enhanced angiogenesis.
      These studies lead to the conclusion that repair potential of MSCs is dependent
      on the age of donors and the repair of senescent infarcted myocardium requires
      young healthy MSCs.

PMID- 20041971
TI  - FXR an emerging therapeutic target   for the treatment of atherosclerosis.
AB  - Atherosclerosis is the leading cause of illness and death. Therapeutic strategies
      aimed at reducing cholesterol plasma levels have shown efficacy in either
      reducing progression of atherosclerotic plaques and atherosclerosis-related
      mortality. The farnesoid-X-receptor (FXR) is a member of metabolic nuclear
      receptors (NRs) superfamily activated by bile acids. In entero-hepatic tissues,
      FXR functions as a bile acid sensor regulating bile acid synthesis,
      detoxification and excretion. In the liver FXR induces the expression of an
      atypical NR, the small heterodimer partner, which subsequently inhibits the
      activity of hepatocyte nuclear factor 4alpha repressing the transcription of
      cholesterol 7a-hydroxylase, the critical regulatory gene in bile acid synthesis.
      In the intestine FXR induces the release of fibroblast growth factor 15 (FGF15)
      (or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signalling to
      inhibit bile acid synthesis. In rodents, FXR activation decreases bile acid
      synthesis and lipogenesis and increases lipoprotein clearance, and regulates
      glucose homeostasis by reducing liver gluconeogenesis. FXR exerts counter
      regulatory effects on macrophages, vascular smooth muscle cells and endothelial
      cells. FXR deficiency in mice results in a pro-atherogenetic lipoproteins profile
      and insulin resistance but FXR(-/-) mice fail to develop any detectable plaques
      on high-fat diet. Synthetic FXR agonists protect against development of aortic
      plaques formation in murine models characterized by pro-atherogenetic lipoprotein
      profile and accelerated atherosclerosis, but reduce HDL levels. Because human and
      mouse lipoprotein metabolism is modulated by different regulatory pathways the
      potential drawbacks of FXR ligands on HDL and bile acid synthesis need to
      addressed in relevant clinical settings.

PMID- 20041972
TI  - Molecular characterization and functional properties of cardiomyocytes derived
      from human inducible pluripotent stem cells.
AB  - In view of the therapeutic potential of cardiomyocytes derived from induced
      pluripotent stem (iPS) cells (iPS-derived cardiomyocytes), in the present study
      we investigated in iPS-derived cardiomyocytes, the functional properties related
      to [Ca(2+) ](i) handling and contraction, the contribution of the sarcoplasmic
      reticulum (SR) Ca(2+) release to contraction and the b-adrenergic inotropic
      responsiveness. The two iPS clones investigated here were generated through
      infection of human foreskin fibroblasts (HFF) with retroviruses containing the
      four human genes: OCT4, Sox2, Klf4 and C-Myc. Our major findings showed that iPS
      derived cardiomyocytes: (i) express cardiac specific RNA and proteins; (ii)
      exhibit negative force-frequency relations and mild (compared to adult) post-rest
      potentiation; (iii) respond to ryanodine and caffeine, albeit less than adult
      cardiomyocytes, and express the SR-Ca(2+) handling proteins ryanodine receptor
      and calsequestrin. Hence, this study demonstrates that in our cardiomyocytes
      clones differentiated from HFF-derived iPS, the functional properties related to
      excitation-contraction coupling, resemble in part those of adult cardiomyocytes.

PMID- 20041973
TI  - Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts
      promotes bone regeneration in rats.
AB  - AIM: The aim of the present study was to investigate bone regeneration following
      ex vivo bone morphogenetic protein-2 (BMP-2) gene delivery using human gingival
      fibroblasts (HGFs) in rat calvarial defects. MATERIALS AND METHODS: An 8 mm
      craniotomy defect was created in Sprague-Dawley rats. The animals were divided
      into four groups: (1) non-grafted group, the defect was left empty; (2) collagen
      matrix group, the defect was filled with collagen matrix only; (3) HGF group, the
      defect was filled with non-transduced HGFs on collagen matrix; (4) BMP-2/HGF
      group, the defect was filled with BMP-2 gene-transduced HGFs on collagen matrix.
      Animals were sacrificed at 2 and 4 weeks after surgery, and micro-computed
      tomographic and histologic observations were performed. RESULTS: The BMP-2/HGF
      group showed promoted osseous healing of calvarial defects, as compared with the
      other groups. At both 2 and 4 weeks, regenerated bone area was significantly
      greater in the BMP-2/HGF group than the other three groups. Quite a few number of
      transplanted HGFs were observed within the regenerated bone tissues. CONCLUSIONS:
      The results of this study suggest that ex vivo BMP-2 gene delivery induces
      prominent bone regeneration in vivo and HGFs may be useful as target cells for ex
      vivo gene therapy.

PMID- 20041974
TI  - Masticatory dysfunction is associated with worse functional ability: a population
      based study.
AB  - AIM: Because of the ageing of populations, disability has become an emergent
      problem from the clinical, social, and economic perspectives. Nevertheless, the
      determinants of disability in older subjects are still unclear. We assessed the
      association between self-assessed masticatory dysfunction (MD) and functional
      ability in older subjects. MATERIALS AND METHODS: We analysed data of all 350
      subjects aged 75+ living in Tuscania (Italy). Functional ability was estimated
      using the Katz' activities of daily living (ADLs), and the Lawton and Brody
      instrumental activities of daily living (IADLs) scales. RESULTS: MD was reported
      by 145 (41%) participants. Disability in the ADLs and IADLs was found in 37 (25%)
      and 53 (37%) of participants with MD, respectively, but only in 11 (5%) and 30
      (15%) of the other participants (p<0.001). MD was associated with disability in
      the ADLs [odds ratio (OR)=2.40, 95% confidence interval (CI)=1.05-5.51], and
      IADLs (OR=2.77, 95% CI=1.07-7.16) in logistic regression, after adjusting. The
      association of MD with disability was stronger among subjects aged 80+.
      CONCLUSIONS: MD is independently associated with disability in community-dwelling
      elderly. Further studies are needed to evaluate the impact of early detection and
      correction of MD on the preservation of functional status in older populations.

PMID- 20041975
TI  - A multi-centre and cross-sectional study of dentine hypersensitivity in China.
AB  - AIM: The objective of this study was to establish the prevalence of dentine
      hypersensitivity (DH) in Chinese urban adults and the possible effects of smoking
      on DH. MATERIALS AND METHODS: A total of 2640 subjects were distributed equally
      in 12 communities in Chengdu and Xian City, respectively, and of all age groups
      (10 years for an age group) including the same number of male and female subjects
      in each community. Each subject completed a structured interview and the subjects
      who reported hypersensitivity symptoms were examined with cold air from a dental
      triple syringe in order to confirm the diagnosis of DH. Attachment loss and
      gingival recession of sensitive teeth were measured by a Williams periodontal
      probe. RESULTS: The diagnosis of DH established following a clinical assessment
      yielded an overall prevalence of 25.5%. The 50-59-year-old age group had the
      greatest number of subjects with DH (p<0.05). 78.6% and 31.4% of sensitive teeth
      were associated with attachment loss and gingival loss, respectively. Subjects
      who smoked did not have more sensitive teeth on average than subjects who did not
      smoke (p>0.05). CONCLUSIONS: The prevalence of DH in a selected community
      population was 25.5%.

PMID- 20041976
TI  - The association of Fcgamma receptor IIIb genetic polymorphism and susceptibility
      to periodontitis in Taiwanese individuals.
AB  - AIM: The allelic polymorphism of FcgammaRIIIb, the neutrophil-specific receptor
      involved in the phagocytosis of immunoglobulin G-opsonized bacteria, has
      functionally distinct capacities that are important in host defence mediated by
      neutrophils. The aim of this study was to identify whether the polymorphism of
      FcgammaRIIIb is associated with periodontitis in Taiwanese individuals. MATERIALS
      AND METHODS: This case-control study included of 93 aggressive periodontitis
      (AgP) patients, 372 chronic periodontitis (CP) patients and 158 healthy controls
      (HC). The FcgammaRIIIb genotypes were determined by PCR using allele-specific
      primers. The risk for periodontitis associated with genotypes was calculated as
      the odds ratio (OR). RESULTS: A significant difference was observed in the
      distribution of the FcgammaRIIIb genotype between either AgP and HC, or AgP and
      CP, but not between CP and HC. The OR for carriage of the NA2 allele
      (NA1NA2+NA2NA2 versus NA1NA1) in AgP was 3.27 [95% confidence interval (CI)=1.57
      7.51, p=0.0027] and 2.94 (95% CI=1.49-6.48, p=0.0037), as compared with HC and
      CP. After adjusting for possible confounding factors, the association was still
      significant. CONCLUSIONS: The results of the present study suggest that subjects
      carrying at least one copy of the FcgammaRIIIb-NA2 allele might be associated
      with susceptibility to AgP. However, the clinical implications of the
      FcgammaRIIIb allelic polymorphism should be determined by further studies.

PMID- 20041977
TI  - Association of Toll-like receptor 9 haplotypes with chronic periodontitis in
      Czech population.
AB  - AIM: Toll-like receptors (TLRs) belong to the pattern recognition receptors
      family of signal molecules that recognize conserved microbial structures. The aim
      of this study was to analyse polymorphisms in the TLR genes and their association
      with chronic periodontitis (CP). MATERIAL AND METHODS: Two polymorphisms
      (2408G/A, i.e. Arg753Gln and -16934A/T) in TLR-2 and three variants (-1486C/T, 
      1237C/T and+2848A/G) in the TLR-9 genes were studied in 222 patients with CP and
      259 unrelated controls. All polymorphisms were detected using the polymerase
      chain reaction-restriction fragment length polymorphism methods. Subgingival
      bacterial colonization was investigated by the VariOr Dento test. RESULTS: No
      significant differences were found in allele and genotype frequencies of all
      polymorphisms between patients and controls. Nevertheless, complex analysis
      revealed differences in TLR9 haplotype frequencies between both groups (p=0.001).
      Specifically, the haplotype T(-1486)/T(-1237)/A(2848) was significantly more
      frequent (9.6%versus 2.8%, p<0.000001) and the haplotype T(-1486)/T(-1237)/G
      (2848) of the TLR9 gene was less frequent (35.9%versus 43.3%, p=0.01) in patients
      than in controls. However, no significant relationships between periodontal
      pathogens, TLR polymorphisms and CP were found. CONCLUSIONS: In conclusion,
      although no significant role of the TLR2 gene in periodontitis was found, our
      results indicate that TLR9 haplotypes may be associated with susceptibility to
      CP.

PMID- 20041978
TI  - Visceral fat area-defined obesity and periodontitis among Koreans.
AB  - AIM: Although the association of periodontitis with body mass index (BMI)-defined
      obesity has been studied, it remains controversial. Hence, this study aims to
      determine whether the obesity is associated with periodontitis among Koreans and
      to determine the most significant indicator of the obesity on the link. MATERIALS
      AND METHODS: From the Sihwa-Banwol Environmental Health Cohort, 1046 subjects 15
      years of age or older were cross-sectionally surveyed. All participants underwent
      periodontal and medical health examinations. Age, gender, monthly family income,
      smoking, drinking, frequency of daily teeth brushing and physical activity were
      evaluated through interviews. The community periodontal index (CPI) was used to
      assess periodontitis. BMI, waist circumference (WC), waist hip ratio and visceral
      fat area (VFA) were used to assess obesity. Multivariate linear and logistic
      regression analyses were applied. RESULTS: BMI, WC and VFA had a dose-effect
      relationship with the number of sextants with periodontitis. Although subgroup
      analysis revealed several significant associations between obesity and
      periodontitis (CPI 3-4), the greatest association between VFA and periodontitis
      was found in males, age 45-54 (odds ratio=3.30; 95% confidence interval: 1.53
      7.09). CONCLUSIONS: Obesity was associated with periodontitis. VFA was the most
      suitable indicator of obesity in relation to periodontitis. Obesity may be a
      substantial risk factor for periodontitis.

PMID- 20041979
TI  - Periodontal health in children exposed to passive smoking.
AB  - AIM: To determine (1) the cotinine levels of saliva, urine and gingival
      crevicular fluid (GCF) of children in families with and without smoking members
      and (2) a possible association between the periodontal health of the children and
      exposure to passive smoking. MATERIAL AND METHODS: The study population comprised
      of 109 children in the age range 6-12 years. Children were classified as exposed
      to passive tobacco smoking (PTS-exposed, n=51) and as unexposed controls (PTS
      unexposed, n=58). Plaque index, gingival index, bleeding on probing, probing
      depth and clinical attachment level (CAL) were recorded. GCF, saliva and urine
      samples were also collected. The levels of cotinine in these fluids were
      determined by enzyme-linked immunosorbent assay. RESULTS: The mean salivary
      cotinine concentration was significantly increased in PTS-exposed children
      compared with PTS-unexposed children (p<0.05). Further, in a dose-dependent way,
      the mean salivary concentration was significantly higher in children whose father
      or mother was a smoker (p<0.05) as compared, respectively, with children whose
      fathers and mothers were non-smokers. The mean CAL was significantly less in PTS
      exposed children compared with non-PTS-exposed children (0.09 mm; p<0.05) and
      also in children whose father was a smoker (p<0.05), but not in children whose
      mother was a smoker as compared with non-smoker fathers and mothers,
      respectively. The GCF cotinine levels were below the detection limits with the
      assay method that was used. CONCLUSIONS: We have observed that children who are
      exposed to passive smoking have elevated cotinine levels in their saliva
      concomitant with a lowered CAL.

PMID- 20041981
TI  - Somatostatin actions on rat supraoptic nucleus oxytocin and vasopressin neurones.
AB  - Magnocellular neurones in the supraoptic nucleus (SON) receive major afferent
      inputs from the brainstem that have been implicated in the regulation of oxytocin
      and vasopressin secretion from the posterior pituitary. Notably, at parturition,
      some neurones that project from the nucleus tractus solitarii (NTS) in the
      brainstem directly to the SON are activated. Many of these are noradrenergic and
      regulate oxytocin secretion during parturition, whereas others contain
      somatostatin and their role is unclear. In the present study, we report that, at
      parturition, somatostatin mRNA expression in the NTS is significantly increased
      compared to pregnancy, suggesting an active role for these neurones at that time.
      Intracerebroventricular somatostatin infusion significantly increased plasma
      oxytocin secretion in both virgin female and pregnant rats.
      Intracerebroventricular somatostatin increased SON oxytocin and vasopressin
      neurone firing-rates, and increased Fos expression in the SON and paraventricular
      nucleus and in the subfornical organ. Retrodialysis of somatostatin onto the
      ventrally exposed SON also increased vasopressin neurone firing rate but,
      unexpectedly, decreased oxytocin neurone firing rate. The experiments indicate
      that somatostatin neurones in the NTS are activated during parturition but,
      because the direct effects of somatostatin on oxytocin neurones are inhibitory,
      this direct pathway does not appear to contribute to enhanced oxytocin release at
      this time, although indirect somatostatin effects may do so.

PMID- 20041980
TI  - Significance of Periodontal Risk Assessment in the recurrence of periodontitis
      and tooth loss.
AB  - AIM: To investigate the association of the Periodontal Risk Assessment (PRA)
      model categories with periodontitis recurrence and tooth loss during supportive
      periodontal therapy (SPT) and to explore the role of patient compliance. MATERIAL
      AND METHODS: In a retrospective cohort, PRA was performed for 160 patients after
      active periodontal therapy (APT) and after 9.5 +/- 4.5 years of SPT. The
      recurrence of periodontitis and tooth loss were analysed according to the
      patient's risk profile (low, moderate or high) after APT and compliance with SPT.
      The association of risk factors with tooth loss and recurrence of periodontitis
      was investigated using logistic regression analysis. RESULTS: In 18.2% of
      patients with a low-risk profile, in 42.2% of patients with a moderate-risk
      profile and in 49.2% of patients with a high-risk profile after APT,
      periodontitis recurred. During SPT, 1.61 +/- 2.8 teeth/patient were lost. High
      risk profile patients lost significantly more teeth (2.59 +/- 3.9) than patients
      with moderate- (1.02 +/- 1.8) or low-risk profiles (1.18 +/- 1.9) (Kruskal-Wallis
      test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal
      Wallis test, p=0.0067) more teeth (3.11 +/- 4.5) than patients compliant with SPT
      (1.07 +/- 1.6). CONCLUSIONS: In multivariate logistic regression analysis, a high
      risk patient profile according to the PRA model at the end of APT was associated
      with recurrence of periodontitis. Another significant factor for recurrence of
      periodontitis was an SPT duration of more than 10 years.

PMID- 20041982
TI  - The effects of neurokinin B upon gonadotrophin release in male rodents.
AB  - Growing evidence suggests the tachykinin neurokinin B (NKB) may modulate
      gonadotrophin secretion and play a role in sex-steroid feedback within the
      reproductive axis. NKB signalling has recently been identified as being necessary
      for normal human reproductive function, although the precise mechanisms
      underpinning this role remain to be established. We have used rodents to explore
      further the role of NKB within the reproductive axis. In particular, we have
      studied its interactions with kisspeptin, a neuropeptide essential for
      reproductive function in rodent and human with close anatomical links to NKB
      within the hypothalamus. Intraperitoneal administration of NKB (50 nmol) to male
      mice had no effect on circulating luteinsing hormone (LH) levels and, although
      i.p. kisspeptin (15 nmol) increased LH five-fold, co-administration of NKB and
      kisspeptin was indistinguishable from kisspeptin alone. Intracerebroventricular
      administration of NKB (10 nmol) to male mice also had no effect on LH levels,
      with 1 nmol kisspeptin i.c.v. significantly increasing LH compared to control
      (0.37 +/- 0.18 versus 5.11 +/- 0.28 ng/ml, respectively). Interestingly, i.c.v.
      co-administration of NKB and kisspeptin caused a significant increase in LH
      concentrations compared to kisspeptin alone (8.96 +/- 1.82 versus 5.11 +/- 0.28
      ng/ml respectively). We used hypothalamic explants from rats to assess the effect
      of NKB on gonadotrpohin-releasing hormone (GnRH) secretion ex vivo. Doses of NKB
      up to 1000 nm failed to stimulate GnRH secretion, whereas 100 nm kisspeptin
      robustly increased GnRH secretion. Of note, co-administration of NKB with
      kisspeptin abrogated the effect of kisspeptin, producing no GnRH release above
      basal state. Finally, we analysed the expression of Tac2/Tacr3 (genes encoding
      NKB and NK3R, respectively) within the arcuate nucleus in different nutritional
      states. After a 48-h fast, the expression of both Tac2 and Tacr3 showed a
      significant increase, in contrast to levels of Kiss1 and Kiss1r mRNA, which
      remained unchanged. In male rodent models, NKB and kisspeptin have different
      effects upon gonadotrophin release and appear to interact in a complex manner.

PMID- 20041983
TI  - Gonadotrophin-releasing hormone (GnRH) exerts stimulatory effects on GnRH neurons
      in intact adult male and female mice.
AB  - There is substantial evidence for a role of the neuropeptide gonadotrophin
      releasing hormone (GnRH) in the regulation of GnRH neurone secretion but how this
      is achieved is not understood. We examined here the effects of GnRH on the
      electrical excitability and intracellular calcium concentration ([Ca2+](i)) of
      GnRH neurones in intact adult male and female mice. Perforated-patch
      electrophysiological recordings from GnRH-green fluorescent protein-tagged GnRH
      neurones revealed that 3 nm-3 mum GnRH evoked gradual approximately 3 mV
      depolarisations in membrane potential from up to 50% of GnRH neurones in male and
      female mice. The depolarising effect of GnRH was observed on approximately 50% of
      GnRH neurones throughout the oestrous cycle. However, at pro-oestrus alone, GnRH
      was also found to transiently hyperpolarise approximately 30% of GnRH neurones.
      Both hyperpolarising and depolarising responses were maintained in the presence
      of tetrodotoxin. Calcium imaging studies undertaken in transgenic GnRH-pericam
      mice showed that GnRH suppressed [Ca2+](i) in approximately 50% of GnRH neurones
      in dioestrous and oestrous mice. At pro-oestrus, 25% of GnRH neurones exhibited a
      suppressive [Ca2+](i) response to GnRH, whereas 17% were stimulated. These
      results demonstrate that nm to mum concentrations of GnRH exert depolarising
      actions on approximately 50% of GnRH neurones in males and females throughout the
      oestrous cycle. This is associated with a reduction in [Ca2+](i). At pro-oestrus,
      however, a further population of GnRH neurones exhibit a hyperpolarising response
      to GnRH. Taken together, these studies indicate that GnRH acts predominantly as a
      neuromodulator at the level of the GnRH cell bodies to exert a predominant
      excitatory influence upon GnRH neurones in intact adult male and female mice.

PMID- 20041984
TI  - The effect of betamethasone treatment on neuroactive steroid synthesis in a
      foetal Guinea pig model of growth restriction.
AB  - There are ongoing concerns that antenatal corticosteroids, which are administered
      to women at high risk of delivering preterm to reduce the incidence of
      respiratory distress syndrome, have adverse effects on foetal brain development
      and subsequent effects on behaviour and learning, when administered as repeated
      courses. The present study aimed to examine whether repeated betamethasone
      treatment alters the expression of the key-rate limiting enzyme, 5alpha
      reductase, in the synthetic pathway of the potent neuroactive steroid
      allopregnanolone in the brain and placenta and whether this effect is potentiated
      in growth restricted foetuses. To investigate this, pregnant guinea pigs carrying
      either control (sham surgery) or growth-restricted foetuses were treated with
      vehicle or betamethasone (1 mg/kg/day) for 4 days prior to sacrifice (65d).
      Placental insufficiency was induced by the ablation of uterine artery branches
      supplying each placenta at mid gestation, resulting in foetal growth restriction
      characterised by 'brain sparing'. Real-time reverse transcriptase polymerase
      chain reaction was used to determine relative 5alpha-reductase type 1 and 2 mRNA
      expression in the placenta and brain. Immunohistochemistry was used to examine
      the glial fibrillary acidic protein (GFAP) expression in the subcortical white
      matter, CA1 and dentate regions of the hippocampus. 5alpha-reductase type 2 mRNA
      expression in the brain was markedly reduced by betamethasone treatment in male
      foetuses compared to vehicle-treated controls but not in female foetuses. In
      addition, 5alpha-reductase type 1 expression in the brain was increased by growth
      restriction and/or betamethasone treatment in female foetuses but expression in
      males foetuses did not increase. 5alpha-reductase type 2 expression in the
      placenta was markedly reduced by betamethasone treatment compared to vehicle
      treated control. Intrauterine growth restriction and betamethasone treatment
      reduced GFAP expression in the CA1 region of the hippocampus in the brains of
      male but not female foetuses. These data indicate that betamethasone treatment
      suppresses placental expression and has sexually dimorphic effects on expression
      of neuroactive steroid synthetic enzymes in the brain. These actions may lead to
      adverse effects on the developing brain, particularly in male foetuses, such as
      the observed effects on GFAP expression.

PMID- 20041985
TI  - The nature of the compensatory response to low thyroid hormone in the developing
      brain.
AB  - Thyroid hormone is essential for normal brain development, although the degree to
      which the developing brain is sensitive to small perturbations in serum thyroxin
      is not clear. An important concept related to this is that the developing brain
      possesses potent mechanisms to compensate for low serum thyroid hormone, and this
      concept is routinely employed in discussions concerning clinical treatments or
      public health. However, experimental studies have not directly tested whether (or
      the degree to which) putative compensatory mechanisms can ameliorate the
      consequences of small reductions in serum thyroxin (T(4)). To formally test this
      concept, we employed a model of graded T(4) reductions using doses of
      propylthiouracil (PTU) that were 200- to 67-fold lower than the dose
      traditionally used to produce hypothyroidism in rats. PTU produced a stepwise
      decrease in serum total T(4), and a stepwise increase in serum thyroid
      stimulating hormone (TSH), in type 2 deiodinase mRNA expression and enzyme
      activity in the brain, and in the expression of the mRNA encoding the tri
      iodothyronine (T(3)) transporter MCT8 in the postnatal day (P) 15 cortex.
      However, the mRNA encoding RC3/neurogranin, a direct target of T(3) action,
      exhibited a strong negative linear correlation with serum total T(4) despite
      these adaptive responses. In addition, single-cell analysis of RC3 mRNA levels in
      cortical neurones demonstrated that the co-expression of MCT8 did not alter the
      relationship between RC3 mRNA and serum T(4). These findings do not support the
      currently envisioned concept of the developing brain being capable of
      compensating for low T(4).

PMID- 20041986
TI  - Differential effects of melatonin on amyloid-beta peptide 25-35-induced
      mitochondrial dysfunction in hippocampal neurons at different stages of culture.
AB  - beta-Amyloid (Abeta) is strongly involved in the pathogenesis of Alzheimer's
      disease (AD), and mitochondria play an important role in neurodegenerative
      disorders. To determine whether any different effect of melatonin on cultured
      neurons treated with Abeta in vitro and which may be produced through its
      different action on mitochondria at different stages of culture, we investigated
      the damage of cultured rat hippocampal neurons mitochondrial function induced by
      Abeta in young neurons [days in vitro 10 (DIV 10)] and senescent neurons (DIV 25)
      and the protective effect of melatonin. Rat hippocampal neurons were incubated
      with amyloid-beta peptide 25-35 (Abeta25-35) alone or pretreatment with
      melatonin. Cell viability, mitochondrial membrane potential (Deltapsim), ATP and
      the activity of the respiratory chain complexes were measured. Data showed that
      Abeta25-35 caused a reduction in Deltapsim, inhibited the activity of the
      respiratory chain complexes and led to ATP depletion, melatonin attenuated
      Abeta25-35-induced mitochondrial impairment in young neurons, whereas melatonin
      had no effect on Abeta25-35-induced mitochondrial damage in senescent neurons.
      These results demonstrate that melatonin has differential effect on Abeta25-35
      induced mitochondrial dysfunction at different stages of culture and suggest that
      melatonin is useful for the prevention of AD, rather than treatment.

PMID- 20041987
TI  - Melatonin interactions with blood pressure and vascular function during L-NAME
      induced hypertension.
AB  - The mechanisms responsible for the antihypertensive effect of melatonin are not
      completely understood. To elucidate the possible role of the nitric oxide (NO)
      pathway in the hemodynamic actions of melatonin, the effects of this indolamine
      on vascular function during hypertension induced by the NO-synthase (NOS)
      inhibitor, N(omega)-nitro-L-arginine-methyl ester (L-NAME) were investigated.
      Four groups of male adult Wistar rats were employed: control, L-NAME (40 mg/kg),
      melatonin (10 mg/kg) and L-NAME + melatonin for 5 wks. Systolic and diastolic
      blood pressure were measured invasively in the carotid artery. Conjugated dienes
      concentration (an oxidative load marker), NOS RNA expression and its activity and
      RNA expression of cyclooxygenase-(COX)-1 and COX-2 were determined in the aorta.
      Acetylcholine-induced responses and their NO-mediated component were evaluated in
      femoral and mesenteric artery. Moreover, endothelium-derived constricting factor
      (EDCF)-dependent vasoconstriction and inner diameter were determined in the
      femoral artery. Chronic L-NAME treatment induced hypertension, elevated the
      oxidative load and inhibited NOS activity. Moreover, impaired NO-dependent
      relaxation, augmented EDCF-constriction, increased COX-2 expression and reduced
      arterial inner diameter were observed. Melatonin added to L-NAME treatment
      completely prevented elevation of the oxidative load in the aorta. However,
      melatonin was not able to prevent NOS activity decline, elevation of COX-2
      expression or the impairment of vascular responses (except moderate improvement
      in relaxation of small mesenteric arteries) and it exerted only slight
      antihypertensive effect. In conclusion, in addition to the reduction of the
      oxidative load, the restoration of the NO pathway seems to play an important role
      in the antihypertensive effect of melatonin.

PMID- 20041988
TI  - Melatonin-induced calbindin-D9k expression reduces hydrogen peroxide-mediated
      cell death in rat pituitary GH3 cells.
AB  - In this study, we investigated whether calbindin-D9k (CaBP-9k) expression was
      regulated by melatonin during hydrogen peroxide (H(2)O(2))-induced cell death in
      rat pituitary GH3 cells. CaBP-9k expression was increased by melatonin in a dose-
      and time-dependent manner, indicating that CaBP-9k expression is regulated by
      melatonin. Cell survival was increased approximately 27-30% where H(2)O(2)
      treated cells (0.25 or 0.5 mm) were also incubated with 1 mm melatonin, when
      compared with H(2)O(2) alone or H(2)O(2) plus 0.5 mm melatonin. This result was
      consistent with 4,6-diamidino-2-phenylindole staining. CaBP-9k expression was
      also augmented by co-treatment with H(2)O(2) and 1 mm melatonin, suggesting a
      functional relationship between increased cell death and melatonin-induced CaBP
      9k expression during H(2)O(2)-mediated apoptosis. Bcl-2-associated protein
      expression increased following treatment with H(2)O(2) alone, whereas Bcl-2
      expression was elevated following treatment with melatonin alone, or H(2)O(2)
      plus melatonin. The expression of p53 was depressed by treatment with melatonin
      alone, or co-treatment with H(2)O(2) plus melatonin. These results correlated
      with CaBP-9k expression levels and activation of the mitogen-activated protein
      kinase/extracellular signal-regulated kinase signaling pathway. Knockdown of CaBP
      9k expression using a small inhibitory RNA resulted in an elevation of H(2)O(2)
      induced cell death, whereas cell survival was increased in cells that
      overexpressed CaBP-9k, providing additional evidence that the induction of CaBP
      9k expression may be associated with survival signaling during H(2)O(2)-mediated
      oxidative cell death. CaBP-9k appears to interact with p53, suggesting a possible
      role for this interaction in cell proliferation and cell cycle progression.

PMID- 20041989
TI  - Cryptosporidiosis in people: it's not just about the cows.
AB  - Cryptosporidiosis is one of the most common causes of infectious diarrhea in
      people. Although dairy calves are high-risk hosts, the role of other livestock,
      pets, and humans in the disease should not be underestimated. Some
      Cryptosporidium species and strains are specific to people, others are specific
      to animals while some are zoonotic pathogens. Cryptosporidium hominis is the
      species responsible for the majority of human cases in the United States, Sub
      Saharan Africa, and Asia, while Cryptosporidium parvum accounts for more human
      cases in Europe and particularly in the United Kingdom. A deeper understanding of
      Cryptosporidium host range, reservoirs, and transmission is needed to develop
      preventive strategies to protect the general public.

PMID- 20041990
TI  - Urinary markers in healthy young and aged dogs and dogs with chronic kidney
      disease.
AB  - BACKGROUND: Blood urea nitrogen and serum creatinine concentrations only detect a
      decrease of > 75% of renal functional mass. Therefore, there is a need for
      markers that allow early detection and localization of renal damage. HYPOTHESIS:
      Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein
      (uRBP), and N-acetyl-beta-D-glucosaminidase (uNAG) concentrations are increased
      in dogs with chronic kidney disease (CKD) compared with healthy controls and in
      healthy older dogs compared with young dogs. ANIMALS: Ten dogs with CKD, 10
      healthy young dogs (age 1-3 years), and 10 healthy older dogs (age > 7 years)
      without clinically relevant abnormalities on physical examination, hematology,
      biochemistry, and urinalysis. METHODS: Urinary markers were determined using an
      ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related
      to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test
      were used to compare the different groups of dogs. RESULTS: uALB/c, uRBP/c, and
      uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant
      difference was found for uCRP, which was not detectable in the healthy dogs and
      only in 3 of the CKD dogs. Between the healthy young and older dogs, no
      significant difference was detected for any of the markers. CONCLUSION: The
      urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs
      with CKD compared with healthy controls. Additional studies are needed to
      evaluate the ability of these markers to detect renal disease before the onset of
      azotemia.

PMID- 20041991
TI  - Effects of multiple founder populations on spatial genetic structure of
      reintroduced American martens.
AB  - Reintroductions and translocations are increasingly used to repatriate or
      increase probabilities of persistence for animal and plant species. Genetic and
      demographic characteristics of founding individuals and suitability of habitat at
      release sites are commonly believed to affect the success of these conservation
      programs. Genetic divergence among multiple source populations of American
      martens (Martes americana) and well documented introduction histories permitted
      analyses of post-introduction dispersion from release sites and development of
      genetic clusters in the Upper Peninsula (UP) of Michigan <50 years following
      release. Location and size of spatial genetic clusters and measures of individual
      based autocorrelation were inferred using 11 microsatellite loci. We identified
      three genetic clusters in geographic proximity to original release locations.
      Estimated distances of effective gene flow based on spatial autocorrelation
      varied greatly among genetic clusters (30-90 km). Spatial contiguity of genetic
      clusters has been largely maintained with evidence for admixture primarily in
      localized regions, suggesting recent contact or locally retarded rates of gene
      flow. Data provide guidance for future studies of the effects of permeabilities
      of different land-cover and land-use features to dispersal and of other biotic
      and environmental factors that may contribute to the colonization process and
      development of spatial genetic associations.

PMID- 20041992
TI  - Finding candidate genes under positive selection in Non-model species: examples
      of genes involved in host specialization in pathogens.
AB  - Numerous genes in diverse organisms have been shown to be under positive
      selection, especially genes involved in reproduction, adaptation to contrasting
      environments, hybrid inviability, and host-pathogen interactions. Looking for
      genes under positive selection in pathogens has been a priority in efforts to
      investigate coevolution dynamics and to develop vaccines or drugs. To elucidate
      the functions involved in host specialization, here we aimed at identifying
      candidate sequences that could have evolved under positive selection among
      closely related pathogens specialized on different hosts. For this goal, we
      sequenced c. 17,000-32,000 ESTs from each of four Microbotryum species, which are
      fungal pathogens responsible for anther smut disease on host plants in the
      Caryophyllaceae. Forty-two of the 372 predicted orthologous genes showed
      significant signal of positive selection, which represents a good number of
      candidate genes for further investigation. Sequencing 16 of these genes in 9
      additional Microbotryum species confirmed that they have indeed been rapidly
      evolving in the pathogen species specialized on different hosts. The genes
      showing significant signals of positive selection were putatively involved in
      nutrient uptake from the host, secondary metabolite synthesis and secretion,
      respiration under stressful conditions and stress response, hyphal growth and
      differentiation, and regulation of expression by other genes. Many of these genes
      had transmembrane domains and may therefore also be involved in pathogen
      recognition by the host. Our approach thus revealed fruitful and should be
      feasible for many non-model organisms for which candidate genes for diversifying
      selection are needed.

PMID- 20041993
TI  - Translocator hunt comes full Cir-Col.
AB  - The ability of Escherichia coli to kill other E. coli using protein antibiotics
      known as colicins has been known for many years, but the mechanisms involved
      poorly understood. Recent progress has been rapid, however, particularly
      concerning events on either side of the outer membrane (OM). Structures of
      colicins bound to OM receptors have been determined and we have detailed
      mechanistic information on how colicins subvert the periplasmic complexes of
      TolQRAB/Pal or TonB/ExbB/ExbD to trigger cell entry. In this issue of Molecular
      Microbiology, Jakes and Finkelstein answer a long-standing problem concerning the
      uptake mechanism of the pore-forming colicin ColIa: How does the TonB box of the
      colicin cross the OM following high-affinity binding of ColIa to its primary
      receptor, the siderophore transporter Cir? Through a series of chimeric protein
      constructions tested for their activity against a range of mutants and in cell
      death protection assays, the authors come up with the surprising observation that
      following binding of ColIa to Cir it recruits another Cir protein as its OM
      translocator. Not only does this settle various conundrums in the literature, but
      the translocation mechanism that stems from their study will likely be applicable
      to many TonB-dependent colicins.

PMID- 20041994
TI  - Rhodotorula mucilaginosa catheter-related fungaemia in a patient with multiple
      myeloma.
AB  - To date, there have been several case reports of Rhodotorula infection in
      haematological patients, but none affecting patients with multiple myeloma (MM).
      We describe a 54-year-old man with MM receiving prophylaxis with fluconazole who
      was using a subclavian Port-A-Cath and presented two episodes of fungaemia caused
      by Rhodotorula mucilaginosa. The first episode was resolved with oral
      itraconazole and neutropenia recovery. During the second episode, caspofungin was
      administered without success; however, liposomal amphotericin B and catheter
      withdrawal resolved the fungaemia. As far as we know, this is the first case
      reported of R. mucilaginosa fungaemia in a patient with MM.

PMID- 20041995
TI  - Successful management of invasive aspergillosis presenting as pericarditis in an
      adult patient with chronic granulomatous disease.
AB  - Invasive aspergillosis (IA) is a major cause of death among patients with chronic
      granulomatous disease (CGD). Few cases of cardiac aspergillosis have been
      published on CGD patients. Diagnosis of IA in CGD patients can be hampered by
      lack of characteristic symptoms and clinical signs and the serum galactomannan
      assay is often negative. We report the first CGD patient with IA presenting as
      pericarditis where combined antifungal therapy resulted in a successful outcome.

PMID- 20041996
TI  - Dermatophytes as a cause of epizoonoses in dairy cattle and humans in Iran:
      epidemiological and clinical aspects.
AB  - Zoophilic dermatophytosis is a major public and veterinary health problem
      globally widespread among cattle. To identify the causative agent and
      geographical distribution of dermatophytes involved in cattle ringworm and to
      establish if they would be related to human diseases in Iran, a study was carried
      out on 6789 heads of cows and 130 herdsmen during 2006-2007. Samples were taken
      from 380 cattle and 43 herdsmen with suspected dermatophytosis. The causative
      agents were identified macroscopically and microscopically by KOH examination and
      culture isolation. Only 352 cases of dermatophytosis were identified in cattle
      and Trichophyton verrucosum was the exclusive fungus isolated from animals.
      Moreover, 27 cases of human dermatophytosis were identified and T. verrucosum was
      the prevalent causative agent for dermatophytosis in the body, scalp, foot, nail
      and groin of the patients. The obtained results showed that T. verrucosum was the
      predominant cause of dermatophytosis in livestock and dairy farmers. There is a
      scarcity of information on isolation and identification of the epizoonotic agents
      of dermatophytoses in cattle in Iran. This study showed the occurrence of
      dermatophytosis in humans and cattle and confirms that the dermatozoonoses are
      responsible for predominant forms of the disease in people who were in contact
      with cattle.

PMID- 20041997
TI  - Environmental influences on food security in high-income countries.
AB  - Food security is a fundamental human right yet many people are food insecure,
      even in high-income countries. Reviewed here is the evidence for the physical,
      economic, sociocultural, and political environmental influences on household food
      security in high-income countries. The literature was evaluated using the ANGELO
      framework, which is a lens developed for understanding the environmental factors
      underpinning the obesity pandemic. A review of the literature identified 78
      articles, which mostly reported on cross-sectional or qualitative studies. These
      studies identified a wide range of factors associated with food security.
      Foremost among them was household financial resources, but many other factors
      were identified and the complexity of the issue was highlighted. Few studies were
      prospective and even fewer tested the use of interventions other than the
      supplemental nutrition assistance program to address food security. This
      indicates a solution-oriented research paradigm is required to identify effective
      interventions and policies to enhance food security. In addition, comprehensive
      top-down and bottom-up interventions at the community and national levels are
      urgently needed.

PMID- 20041999
TI  - Modulation of pattern recognition receptor-mediated inflammation and risk of
      chronic diseases by dietary fatty acids.
AB  - Chronic inflammation is known to promote the development of many chronic
      diseases. Pattern recognition receptors (PRRs), Toll-like receptors (TLRs), and
      nucleotide-binding oligomerization domain proteins (NODs) mediate both infection
      induced inflammation and sterile inflammation by recognizing pathogen- associated
      molecular patterns and endogenous molecules, respectively. PRR-mediated
      inflammation is an important determinant in altering the risk of many chronic
      diseases. Saturated fatty acids (SFAs) can activate PRRs, leading to enhanced
      expression of pro-inflammatory target gene products. However, n-3 polyunsaturated
      fatty acids (PUFAs) inhibit agonist-induced activation of PRRs. These results
      suggest that SFAs and n-3 PUFAs can reciprocally modulate PRR-mediated
      inflammation, and that PRRs and their downstream signaling components are
      molecular targets for dietary strategies to reduce chronic inflammation and
      subsequent risk of chronic diseases. This advancement in knowledge provides a new
      paradigm for understanding the mechanism by which different dietary fatty acids
      modify risk of chronic diseases including insulin resistance, atherosclerosis,
      and cancer.

PMID- 20042000
TI  - Perchlorate consumption, iodine status, and thyroid function.
AB  - Perchlorate inhibits the uptake of iodide into the thyroid gland, thereby
      possibly affecting the synthesis of thyroid hormones. Pregnant women and their
      fetuses and newborns have the greatest potential for risk of adverse health
      effects following exposure to perchlorate. Perchlorate is present in some foods
      and in drinking water in certain areas of the United States. Based on the
      available information, the United States Food and Drug Administration (FDA) is
      not recommending that consumers of any age alter their diet or eating habits due
      to perchlorate exposure. If one eats a healthy diet that is consistent with the
      Dietary Guidelines for Americans, taking iodine supplements is not necessary for
      protection against health effects associated with perchlorate at the levels
      present in water and foods.

PMID- 20041998
TI  - Low zinc status: a new risk factor for pneumonia in the elderly?
AB  - Low zinc status may be a risk factor for pneumonia in the elderly. This special
      article reviews the magnitude of the problem of pneumonia (its prevalence,
      morbidity, and mortality) in the elderly, pneumonia's etiology, and the
      dysregulation of the immune system associated with increasing age. In addition,
      recent evidence from the literature is presented demonstrating that low zinc
      status (commonly reported in the elderly) impairs immune function, decreases
      resistance to pathogens, and is associated with increased incidence and duration
      of pneumonia, increased use and duration of antimicrobial treatment, and
      increased overall mortality in the elderly. Inadequate stores of zinc might,
      therefore, be a risk factor for pneumonia in the elderly. Randomized, double
      blind, controlled studies are needed to determine the efficacy of zinc
      supplementation as a potential low-cost intervention to reduce morbidity and
      mortality due to pneumonia in this vulnerable population.

PMID- 20042001
TI  - Retinoic acid activation of peroxisome proliferation-activated receptor delta
      represses obesity and insulin resistance.
AB  - Retinoic acid (RA) was found to be a ligand for peroxisome proliferation
      activated receptor delta (PPARdelta) as well as the classical RA receptor (RAR).
      Carrier proteins that move the RA from the cytosol into the nucleus are the fatty
      acid-binding protein 5 (FABP5), activating PPARdelta, and the cellular retinoic
      acid-binding protein II (CRABPII), activating RAR. The ratio of FABP5/CRABPII
      concentrations determines which receptor is activated. By activating PPARdelta,
      RA was found to induce expression of genes affecting lipid and glucose
      homeostasis, in particular, leading to expression of the insulin-signaling gene
      PDK1 and improvement of insulin action. Hence, RA stimulates lipolysis and
      reduces triglyceride content. In vivo, obesity has led to downregulation of
      adipose PPARdelta expression. RA implantation into obese mice has caused
      upregulation of levels of PPARdelta and consequent weight loss as well as
      increased expression of PPARdelta target genes, including the insulin-signaling
      gene PDK1.

PMID- 20042003
TI  - Granulocytes: effector cells or immunomodulators in the immune response to
      helminth infection?
AB  - Granulocytes are effector cells in defence against helminth infections. We review
      the current evidence for the role of granulocytes in protective immunity against
      different helminth infections and note that for each parasite species the role of
      granulocytes as effector cells can vary. Emerging evidence also points to
      granulocytes as immunomodulatory cells able to produce many cytokines, chemokines
      and modulatory factors which can bias the immune response in a particular
      direction. Thus, the role of granulocytes in an immunomodulatory context is
      discussed including the most recent data that points to an important role for
      basophils under this guise.

PMID- 20042004
TI  - Detection of the Sm31 antigen in sera of Schistosoma mansoni- infected patients
      from a low endemic area.
AB  - Schistosoma mansoni cathepsin B (Sm31) is a major antigen from adult worms that
      circulates in the blood of infected patients (Li et al., Parasitol Res 1996; 82:
      14-18). An analysis of the Sm31 sequence (Klinkert et al., Mol Biochem Parasitol
      1989; 33: 113-122) allowed the prediction of seven hydrophilic regions that were
      confirmed to be exposed on the surface of a 3D model of Sm31; the species
      specificity of these regions was checked using BLAST analysis. The corresponding
      peptides were chemically synthesized in polymerazible forms using the t-Boc
      technique. Rabbits developed a high humoral response against these peptides as
      tested by a multiple antigen blot assay; it recognized native Sm31 in crude S.
      mansoni extracts and as circulating antigen in sera of S. mansoni-infected
      patients by western blot. Relevant antigenic determinants were located at the N-
      and C-terminus sequences. Antibodies against these regions recognized the native
      enzyme in an ELISA-like assay called cysteine protease immuno assay in which the
      immunocaptured enzyme was revealed by the intrinsic cathepsin B hydrolytic
      activity of Sm31. The method successfully and specifically detected Sm31 in sera
      of infected individuals, most of them (83.3%) with light infections, offering a
      rationale for the development of parasite enzyme capture assays using anti
      synthetic peptide antibodies for possible use in the diagnosis of
      schistoso,iasis.

PMID- 20042005
TI  - Experimental infection of chickens with Histomonas meleagridis confirms the
      presence of antibodies in different parts of the intestine.
AB  - Specific pathogen-free chickens were infected with a clonal culture of the
      protozoan parasite, Histomonas meleagridis. Severe lesions were found within the
      caeca of all birds euthanized at 7 and 14 days post-infection (d.p.i.). Following
      necropsy of birds, intestinal samples were taken to establish ex vivo tissue
      cultures to determine the IgG, IgA and IgM antibody levels in the supernatants
      before and after incubation with a recently established ELISA. Presence of
      antibodies was also determined in the sera and first optical density values for
      IgG above the cut-off were detected at 14 d.p.i. IgA levels remained low in the
      serum with a small peak 4 weeks p.i., a phenomenon also found for IgM. The
      intestinal tissue samples showed very strong immunological reactions in the
      parasitized caeca with an initial peak of IgM, high levels of IgG and a
      continuous increase of IgA. In the duodena and jejuna, IgA values reached similar
      high levels as those obtained in the caeca, whereas IgG and IgM increased only
      slightly.

PMID- 20042006
TI  - Nematode challenge induces differential expression of oxidant, antioxidant and
      mucous genes down the longitudinal axis of the sheep gut.
AB  - To characterize the role of a range of oxidant, antioxidant and mucous-related
      genes in the primary response to gastrointestinal nematodes, groups of
      genetically resistant sheep were challenged with either Haemonchus contortus or
      Trichostrongylus colubriformis and necropsied for retrieval of tissue at days 0,
      3, 7, 14 and 21. To determine if the response was localized to the site of
      parasite infection, four different gut tissues were sampled: the abomasum,
      proximal and distal jejunum and ileum. Basal expression patterns of all candidate
      genes were determined using the day 0 (pre-challenge) samples. A conserved innate
      response involving elevated expression of dual oxidase, glutathione peroxidase
      and trefoil factor was initiated within 3 days of challenge and extended out to
      21 days. An increase in host gene expression levels at the preferred site of
      infection (the abomasum for H. contortus and the proximal jejunum for T.
      colubriformis) was also common to both nematodes. However, these increases were
      concomitant with reduced expression in other areas of the gut suggesting a
      compartmentalized response. Other aspects of the response were parasite-specific,
      with T. colubriformis challenge inducing expression peaks at times corresponding
      to nematode life-stage transitions.

PMID- 20042007
TI  - The mucosal response to secondary infection with Ancylostoma ceylanicum in
      hamsters immunized by abbreviated primary infection.
AB  - We assessed the mucosal response of previously infected hamsters to low-dose
      challenge with the hookworm, Ancylostoma ceylanicum. Hamsters were assigned to
      five treatment groups (Groups 1-5, respectively): naive, controls; uninterrupted
      primary infection from day 0; infected, but treated with anthelmintic on day 35
      p.i.; challenge control group given only the second infection on day 63; infected
      initially, cleared of worms and then challenged. Animals were culled on days 73
      and 94 (10 and 31 days after challenge), but additional animals were culled from
      Group 5 on days 80 and 87. The results showed that villus height declined
      markedly and progressively over time after challenge in Group 5, whilst depth of
      the Crypts of Lieberkuhn and number of mitotic figures in the crypts increased.
      Mucosal mast cell numbers were only marginally higher than those in naive
      controls and not as high as those in mice with uninterrupted infections. Goblet
      cell counts showed a major increase, as did eosinophils in relation to naive
      controls. Paneth cells were also elevated, but did not change over the course of
      the experiment. The results also drew attention to the tremendous resilience of
      hookworms, some adult worms surviving throughout, despite highly inflamed
      intestines.

PMID- 20042008
TI  - Helminth infection inhibits airway allergic reaction and dendritic cells are
      involved in the modulation process.
AB  - Several previous studies have demonstrated that some helminth infections can
      inhibit allergic reactions, but the examination on the effect of live Schistosoma
      japonicum (SJ) infection on allergic inflammation remains limited. The aim of
      this study was to examine the effect and mechanism of chronic SJ infection on
      airway allergic inflammation in a murine model. The data showed that chronic SJ
      infection suppressed airway eosinophilia, mucus production and antigen-specific
      IgE responses induced by ovalbumin (OVA) sensitization and challenge. Cytokine
      production analysis showed that chronic SJ infection reduced allergen-driven
      interleukin (IL)-4 and IL-5 production, but had no significant effect on IFN
      gamma production. More importantly, we found that the adoptive transfer of
      dendritic cells (DCs) from SJ-infected mice dramatically decreased airway
      allergic inflammation in the recipients, which was associated with significant
      decrease of IL-4/IL-5 production and increase of IL-10 production. The results
      suggest that SJ infection may inhibit the development of allergy and that DCs may
      be involved in the process of helminth infection-mediated modulation of allergic
      inflammation.

PMID- 20042009
TI  - Different Th1/Th2 responses to Anisakis simplex are related to distinct clinical
      manifestations in sensitized patients.
AB  - Anisakis simplex is a fish parasite capable of inducing inflammatory and allergic
      reactions in humans who eat raw or undercooked fish. The aim of this study was to
      characterize the T helper type 1 (Th1)/Th2 immune response to parasite crude (CE)
      and thermostable (TsE) extracts in A. simplex-sensitized patients. Cytokines were
      quantified by a multiplex flow cytometric method in short-term whole blood
      cultures. Higher concentrations of IL-2, IL-4 and IL-5, measured with the CE and
      TsE, were found in patients than in controls. Patients showing urticaria-angio
      oedema or anaphylaxis (UA/A) had higher total and specific IgE levels than those
      with gastrointestinal symptoms (GI). The UA/A group showed high levels of IL-5
      and IL-4 and low expression of IFN-gamma than the GI group. The GI group had
      significantly higher IFN-gamma/IL4 ratio than the UA/A group. Four patients with
      severe GI symptoms reporting a delayed skin test reaction had very low values of
      specific IgE to A. simplex and higher IFN-gamma/IL4 ratios than that observed in
      other patients belonging to the GI group. This short-term whole blood test can be
      useful for immune response characterization in Anisakis infection and showed that
      heated parasite antigens are still capable of inducing cellular immune response
      in sensitized patients.

PMID- 20042011
TI  - Do helminths cause epilepsy? The case of Onchocerca volvulus.

PMID- 20042010
TI  - Recovery from Strongyloides venezuelensis infection in Lewis rats is associated
      with a strong Th2 response.
AB  - In this study, we investigated the characteristics of the infection and
      subsequent immunity induced by Strongyloides venezuelensis in Lewis rats. Animals
      were infected with 4000 L3 of S. venezuelensis and number of eggs per gram of
      faeces indicated an acute phase around day 8 and a recovery phase around day 32
      after infection. A strong Th2 polarization during recovery phase was ascertained
      by a significant increase in IgG1 and IgE compared with that in the acute period.
      A shift in the cytokine profile confirmed these findings. A predominant
      production of IFN-gamma during the acute phase was followed by IL-10 production
      during recovery. Together these findings show that experimental infection of
      Lewis rats with S. venezuelensis presents a kinetics of parasite establishment
      and immunity similar to that described in other models of helminthic infection.

PMID- 20042012
TI  - Prevalence of hepatic abnormalities in a cohort of Egyptian children with type 1
      diabetes mellitus.
AB  - BACKGROUND AND AIM: Children with type 1 diabetes mellitus (T1DM) are frequently
      investigated for hepatic abnormalities. This study was carried out to report on
      the prevalence of hepatic abnormalities in diabetic children and adolescents and
      to highlight the possible etiology and appropriate management. METHODS: The study
      included 692 children (333 were males) with T1DM attending the Diabetes Unit at
      Cairo University Pediatric Hospital. Their mean age was 9.65 +/- 4.18 yr. All
      children were subjected to clinical examination for hepatomegaly, determination
      of alanine aminotransferase (ALT) and antibodies to hepatitis C virus (anti-HCV),
      and abdominal ultrasonography. All children with clinical, laboratory or
      ultrasound abnormality were counseled about proper glycemic control and followed
      up. If abnormalities persisted, more detailed investigations were carried out.
      HCV RNA was done for anti-HCV positive children. RESULTS: Sixty (8.7%) were found
      to have one or more abnormalities: clinical hepatomegaly in 13 (1.9%), elevated
      ALT in 27 (3.9%), anti-HCV in 25 (3.6%) and abnormal hepatic ultrasound in 31
      (4.5%). Forty percent of anti-HCV positive children were HCV-RNA positive.
      Glycogenic hepatopathy was diagnosed in three cases by liver biopsy.
      Abnormalities were reversible in 37/60 after proper glycemic control. CONCLUSION:
      Although diabetic children are at risk of acquisition of HCV, poor glycemic
      control is the key factor that predisposes to hepatomegaly, elevated ALT and
      abnormal ultrasound findings. A 4 to 8-wk therapeutic trial of proper glycemic
      control is recommended prior to more invasive diagnostic procedures.

PMID- 20042013
TI  - Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes
      mellitus in a family carrying the inactivating ABCC8 E1506K mutation.
AB  - Congenital hyperinsulinism of infancy (CHI) is the most common cause of
      hypoglycemia in newborns and infants. Several molecular mechanisms are involved
      in the development of CHI, but the most common genetic defects are inactivating
      mutations of the ABCC8 or KCNJ11 genes. The classical treatment for CHI has been
      pancreatectomy that eventually leads to diabetes. More recently, conservative
      treatment has been attempted in some cases, with encouraging results. Whether or
      not the patients with heterozygous ABCC8 mutations submitted to conservative
      treatment may spontaneously develop type 2 diabetes in the long run, is a
      controversial issue. Here, we report a family carrying the dominant heterozygous
      germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the
      newborn period and diabetes in adulthood. The mutation occurred as a de novo germ
      line mutation in the mother of the index patient. Her hypoglycemic symptoms as a
      child occurred after the fourth year of life and were very mild, but she
      developed glucose metabolism impairment in adulthood. On the other hand, in her
      daughter, the clinical manifestations of the disease occurred in the neonatal
      period and were more severe, leading to episodes of tonic-clonic seizures that
      were well controlled with octreotide or diazoxide. Our data corroborate the
      hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI,
      predisposes to the development of glucose intolerance and diabetes later in life.

PMID- 20042014
TI  - Autonomy and insulin in adolescents with type 1 diabetes.

PMID- 20042015
TI  - Children draw with rulers: a symbolic sign of post-conflict adjustment?

PMID- 20042016
TI  - H1N1 influenza A 2009 and pediatric transplantation: lessons learned and to be
      learned.

PMID- 20042017
TI  - Idiopathic hypereosinophilic syndrome in a case with ABO-incompatible liver
      transplantation for biliary atresia complicated by portal vein thrombosis.
AB  - Idiopathic HES is characterlized by prolonged eosinophilia without an
      identifiable underlying cause and multiple-organ dysfunction. We report a case of
      a LDLT for a 12-yr-old Japanese girl with BA accompanied by HES. Histological
      examination of the resected liver showed biliary cirrhosis with dense
      eosinophilic infiltration of portal tracts and the lobules of the liver. She
      developed portal vein thrombosis on post-operative day 10 and the
      histopathological findings of the thrombus revealed dense eosinophilic
      deposition, suggesting that HES might have influenced the formation of this
      thrombus. Liver graft biopsies also demonstrated the presence of activated
      eosinophilils with biliary damage. Blood chemistry findings suggested liver
      dysfunction as a result of the eosinophilic infiltrations. Prednisolone treatment
      improved the liver dysfunction. Four years after LDLT, she remains clinically
      well on prednisolone at 0.3 mg/kg/day, with an eosinophil count ranging from 10
      to 15%. A literature review has not shown any previous reports of HES with BA.
      This case demonstrates the possibility of an association between eosinophilic
      infiltration and liver dysfunction during follow-up for BA and after LDLT.

PMID- 20042018
TI  - Piecing together the pigment-type switching puzzle.

PMID- 20042019
TI  - Proteasome activity profiling: a simple, robust and versatile method revealing
      subunit-selective inhibitors and cytoplasmic, defense-induced proteasome
      activities.
AB  - The proteasome plays essential roles in nearly all biological processes in plant
      defense and development, yet simple methods for displaying proteasome activities
      in extracts and living tissues are not available to plant science. Here, we
      introduce an easy and robust method to simultaneously display the activities of
      all three catalytic proteasome subunits in plant extracts or living plant
      tissues. The method is based on a membrane-permeable, small-molecule fluorescent
      probe that irreversibly reacts with the catalytic site of the proteasome
      catalytic subunits in an activity-dependent manner. Activities can be quantified
      from fluorescent protein gels and used to study proteasome activities in vitro
      and in vivo. We demonstrate that proteasome catalytic subunits can be selectively
      inhibited by aldehyde-based inhibitors, including the notorious caspase-3
      inhibitor DEVD. Furthermore, we show that the proteasome activity, but not its
      abundance, is significantly increased in Arabidopsis upon treatment with
      benzothiadiazole (BTH). This upregulation of proteasome activity depends on NPR1,
      and occurs mostly in the cytoplasm. The simplicity, robustness and versatility of
      this method will make this method widely applicable in plant science.

PMID- 20042020
TI  - A novel RNA-binding peptide regulates the establishment of the Medicago
      truncatula-Sinorhizobium meliloti nitrogen-fixing symbiosis.
AB  - Plants use a variety of small peptides for cell to cell communication during
      growth and development. Leguminous plants are characterized by their ability to
      develop nitrogen-fixing nodules via an interaction with symbiotic bacteria.
      During nodule organogenesis, several so-called nodulin genes are induced,
      including large families that encode small peptides. Using a three-hybrid
      approach in yeast cells, we identified two new small nodulins, MtSNARP1 and
      MtSNARP2 (for small nodulin acidic RNA-binding protein), which interact with the
      RNA of MtENOD40, an early induced nodulin gene showing conserved RNA secondary
      structures. The SNARPs are acidic peptides showing single-stranded RNA-binding
      activity in vitro and are encoded by a small gene family in Medicago truncatula.
      These peptides exhibit two new conserved motifs and a putative signal peptide
      that redirects a GFP fusion to the endoplasmic reticulum both in protoplasts and
      during symbiosis, suggesting they are secreted. MtSNARP2 is expressed in the
      differentiating region of the nodule together with several early nodulin genes.
      MtSNARP2 RNA interference (RNAi) transgenic roots showed aberrant early senescent
      nodules where differentiated bacteroids degenerate rapidly. Hence, a functional
      symbiotic interaction may be regulated by secreted RNA-binding peptides.

PMID- 20042021
TI  - Up-regulation of LSB1/GDU3 affects geminivirus infection by activating the
      salicylic acid pathway.
AB  - Geminiviruses include a large number of single-stranded DNA viruses that are
      emerging as useful tools to dissect many fundamental processes in plant hosts.
      However, there have been no reports yet regarding the genetic dissection of the
      geminivirus-plant interaction. Here, a high-throughput approach was developed to
      screen Arabidopsis activation-tagged mutants which are resistant to geminivirus
      Beet severe curly top virus (BSCTV) infection. A mutant, lsb1 (less susceptible
      to BSCTV 1), was identified, in which BSCTV replication was impaired and BSCTV
      infectivity was reduced. We found that the three genes closest to the T-DNA were
      up-regulated in lsb1, and the phenotypes of lsb1 could only be recapitulated by
      the overexpression of GDU3 (GLUTAMINE DUMPER 3), a gene implicated in amino acid
      transport. We further demonstrated that activation of LSB1/GDU3 increased the
      expression of components in the salicylic acid (SA) pathway, which is known to
      counter geminivirus infection, including the upstream regulator ACD6. These data
      indicate that up-regulation of LSB1/GDU3 affects BSCTV infection by activating
      the SA pathway. This study thus provides a new approach to study of the
      geminivirus-host interaction.

PMID- 20042022
TI  - Genes of primary sulfate assimilation are part of the glucosinolate biosynthetic
      network in Arabidopsis thaliana.
AB  - Glucosinolates are plant secondary metabolites involved in responses to biotic
      stress. The final step of their synthesis is the transfer of a sulfo group from
      3'-phosphoadenosine 5'-phosphosulfate (PAPS) onto a desulfo precursor. Thus,
      glucosinolate synthesis is linked to sulfate assimilation. The sulfate donor for
      this reaction is synthesized from sulfate in two steps catalyzed by ATP
      sulfurylase (ATPS) and adenosine 5'-phosphosulfate kinase (APK). Here we
      demonstrate that R2R3-MYB transcription factors, which are known to regulate both
      aliphatic and indolic glucosinolate biosynthesis in Arabidopsis thaliana, also
      control genes of primary sulfate metabolism. Using trans-activation assays we
      found that two isoforms of APK, APK1, and APK2, are regulated by both classes of
      glucosinolate MYB transcription factors; whereas two ATPS genes, ATPS1 and ATPS3,
      are differentially regulated by these two groups of MYB factors. In addition, we
      show that the adenosine 5'-phosphosulfate reductases APR1, APR2, and APR3, which
      participate in primary sulfate reduction, are also activated by the MYB factors.
      These observations were confirmed by analysis of transgenic lines with modulated
      expression levels of the glucosinolate MYB factors. The changes in transcript
      levels also affected enzyme activities, the thiol content and the sulfate
      reduction rate in some of the transgenic plants. Altogether the data revealed
      that the MYB transcription factors regulate genes of primary sulfate metabolism
      and that the genes involved in the synthesis of activated sulfate are part of the
      glucosinolate biosynthesis network.

PMID- 20042023
TI  - Automated tracking of stem cell lineages of Arabidopsis shoot apex using local
      graph matching.
AB  - Shoot apical meristems (SAMs) of higher plants harbor stem-cell niches. The cells
      of the stem-cell niche are organized into spatial domains of distinct function
      and cell behaviors. A coordinated interplay between cell growth dynamics and
      changes in gene expression is critical to ensure stem-cell homeostasis and organ
      differentiation. Exploring the causal relationships between cell growth patterns
      and gene expression dynamics requires quantitative methods to analyze cell
      behaviors from time-lapse imagery. Although technical breakthroughs in live
      imaging methods have revealed spatio-temporal dynamics of SAM-cell growth
      patterns, robust computational methods for cell segmentation and automated
      tracking of cells have not been developed. Here we present a local graph matching
      based method for automated-tracking of cells and cell divisions of SAMs of
      Arabidopsis thaliana. The cells of the SAM are tightly clustered in space which
      poses a unique challenge in computing spatio-temporal correspondences of cells.
      The local graph-matching principle efficiently exploits the geometric structure
      and topology of the relative positions of cells in obtaining spatio-temporal
      correspondences. The tracker integrates information across multiple slices in
      which a cell may be properly imaged, thus providing robustness to cell tracking
      in noisy live-imaging datasets. By relying on the local geometry and topology,
      the method is able to track cells in areas of high curvature such as regions of
      primordial outgrowth. The cell tracker not only computes the correspondences of
      cells across spatio-temporal scale, but it also detects cell division events, and
      identifies daughter cells upon divisions, thus allowing automated estimation of
      cell lineages from images captured over a period of 72 h. The method presented
      here should enable quantitative analysis of cell growth patterns and thus
      facilitating the development of in silico models for SAM growth.

PMID- 20042024
TI  - GERMINATOR: a software package for high-throughput scoring and curve fitting of
      Arabidopsis seed germination.
AB  - Over the past few decades seed physiology research has contributed to many
      important scientific discoveries and has provided valuable tools for the
      production of high quality seeds. An important instrument for this type of
      research is the accurate quantification of germination; however gathering
      cumulative germination data is a very laborious task that is often prohibitive to
      the execution of large experiments. In this paper we present the germinator
      package: a simple, highly cost-efficient and flexible procedure for high
      throughput automatic scoring and evaluation of germination that can be
      implemented without the use of complex robotics. The germinator package contains
      three modules: (i) design of experimental setup with various options to replicate
      and randomize samples; (ii) automatic scoring of germination based on the color
      contrast between the protruding radicle and seed coat on a single image; and
      (iii) curve fitting of cumulative germination data and the extraction, recap and
      visualization of the various germination parameters. The curve-fitting module
      enables analysis of general cumulative germination data and can be used for all
      plant species. We show that the automatic scoring system works for Arabidopsis
      thaliana and Brassica spp. seeds, but is likely to be applicable to other
      species, as well. In this paper we show the accuracy, reproducibility and
      flexibility of the germinator package. We have successfully applied it to
      evaluate natural variation for salt tolerance in a large population of
      recombinant inbred lines and were able to identify several quantitative trait
      loci for salt tolerance. Germinator is a low-cost package that allows the
      monitoring of several thousands of germination tests, several times a day by a
      single person.

PMID- 20042025
TI  - Buffalo (Bubalus bubalis) embryonic stem cell-like cells and preimplantation
      embryos exhibit comparable expression of pluripotency-related antigens.
AB  - In this study, inner cell mass (ICM) cells were isolated from in vitro produced
      buffalo blastocysts and were cultured on mitomycin-C treated buffalo foetal
      fibroblast feeder layer for producing embryonic stem (ES) cells. Among different
      sources (hatched vs expanded blastocysts) or methods (enzymatic vs mechanical),
      mechanical isolation of ICM from hatched blastocysts resulted in the highest
      primary colony formation rate and the maximum passage number up to which ES cells
      survived. Putative ES cells expressed alkaline phosphatase and exhibited a normal
      karyotype up to passage 7. Putative ES cells and embryos at 2- to 4-cell, 8- to
      16-cell, morula and blastocyst stages strongly expressed stage-specific embryonic
      antigen (SSEA)-4 but lacked expressions of SSEA-1 and SSEA-3. Putative ES cells
      also expressed tumour rejection antigen (TRA)-1-60, TRA-1-81 and Oct4. Whereas in
      all early embryonic stages, TRA-1-60 was observed only in the periplasmic space,
      and TRA-1-81 expression was observed as small spots at a few places inside the
      embryos, both these markers were expressed by ICM. Oct4 expression, which was
      observed at all the embryonic stages and also in the trophectoderm, was the
      strongest in the ICM. Buffalo putative ES cells possess a unique pluripotency
      related surface antigen phenotype, which resembles that of the ICM.

PMID- 20042026
TI  - Chemical activation with a combination of ionomycin and dehydroleucodine for
      production of parthenogenetic, ICSI and cloned bovine embryos.
AB  - The aim of this study was to evaluate the potential of dehydroleucodine (DhL), a
      new drug isolated from a medicinal herb used in Argentina, for activation of
      bovine oocyte. Several DhL concentrations and exposure times after ionomycin (Io)
      treatment were tested. The optimal DhL treatment, found for parthenogenetic
      development, was employed to produce bovine embryos by intracytoplasmic sperm
      injection (ICSI) and somatic cell nuclear transfer (SCNT). The best parthenogenic
      embryo developments were observed with 5 MUM Io for 4 min followed by 5 MUM DhL
      concentration and after 3-h exposure time (52.3% cleavage; 17.4% morulae; 7.3%
      blastocyst; n = 109). This treatment generated no significant differences with
      standard Io plus 6-dimethylaminopurine (DMAP) treatment in preimplantation embryo
      development. In our conditions, the embryo development reached after ICSI and
      SCNT assisted by the DhL treatment did not differ in terms of cleavage and
      blastocyst development from activation with standard Io plus DMAP treatment (p >
      0.05). In conclusion, DhL utilization to activate oocytes and induce development
      of parthenogenotes, ICSI-embryos or SCNT-embryos is reported here for first time.

PMID- 20042027
TI  - Therapeutic approaches to pregnancy loss of non-infectious cause during the late
      embryonic/early foetal period in dairy cattle. A review.
AB  - The problem of pregnancy loss during the late embryonic/early foetal period due
      to non-infectious causes in dairy cattle is on the rise, especially in high milk
      producing cows. This review discusses recent therapeutic approaches designed to
      reduce the incidence of early foetal loss. These strategies are based on the fact
      that low plasma concentrations of progesterone are commonly related to foetal
      loss. Progesterone supplementation during the late embryonic/early foetal period
      has proven useful in curtailing losses, mainly in single pregnancies, whereas a
      more positive effect of treatment with GnRH than progesterone has been found in
      twin pregnancies. Therapeutics is not necessary in cows with an additional corpus
      luteum. In practical terms, suggestions include recording the number of embryos
      and corpora lutea on first pregnancy diagnosis and checking for normal pregnancy
      progression on day 60 post-insemination.

PMID- 20042028
TI  - Enduring cognitive dysfunction in unipolar major depression: a test-retest study
      using the Stroop paradigm.
AB  - The aim of the study was to investigate automatic and effortful information
      processing with the Stroop paradigm in a long term perspective in patients with
      major depressive disorder (MDD). Patients were tested at two test occasions: at
      inclusion with a Hamilton Depression Rating Scale (HDRS) score >18, and after 6
      months, when most patients had experienced symptom reduction. The Stroop paradigm
      is considered to measure aspects of attention and executive functioning and
      consists of three conditions/cards: naming the color of the patches (Color),
      reading of the color-words (Word) and naming the ink color of color-words (Color
      Word). The Color-Word condition is proved to be the most cognitive demanding task
      and requires the proband to actively suppress interference and is therefore
      considered to require more effortful information processing, whereas naming the
      color of the patches and reading the color-words are expected to be more
      automatic and less cognitive demanding. A homogenous group of 19 patients with
      unipolar recurrent MDD according to DSM-IV and a HDRS score of >18 were included
      in the study. A control group was individually matched for age, gender and level
      of education. Depressed patients performed equal to the control group on the
      Color and Word cards at both test occasions. However, the patients were impaired
      compared with the control group on the Color-Word card task at both test
      occasions. Thus, the depressed patients showed no improvement of effortful
      attention/executive performance as a function of symptom reduction. The results
      indicate that the depressed patients showed impaired cognitive performance on
      cognitive demanding tasks when symptomatic and that this impairment prevailed
      after 6 months, despite significant improvement in their depressive symptoms.

PMID- 20042029
TI  - Association of stress-related perinatal factors and cord blood unit hematopoietic
      progenitors is dependent on delivery mode.
AB  - BACKGROUND: Perinatal characteristics, variably utilized in cord blood (CB)
      selection for banking, affect CB hematopoietic progenitor cells (HPCs). The
      association between perinatal stress factors and CB unit HPCs was evaluated.
      STUDY DESIGN AND METHODS: Umbilical arterial (UA) pH, absolute and relative birth
      weight (BW) and placental weight (PW), and PW/BW ratio of 167 healthy, full-term
      infants were compared with CB unit prefreeze total nucleated cells (TNCs), total
      CD34+ (TCD34+) cells, and total colony-forming unit (CFU-TOT) number. Cesarean
      section (C-section, n = 104) and vaginal delivery subgroups were also analyzed.
      RESULTS: UA pH (median, 7.28; range, 7.04-7.40) correlated with CB unit CFU-TOT
      number (n = 166; r = -0.32, p < 0.0001), TCD34+ cells (r = -0.31, p < 0.0001),
      and TNCs (r = -0.29, p = 0.0002). Similarly, BW, PW, and PW/BW ratio correlated
      with HPCs. In multiple linear regression analysis, CFU-TOT number was predicted
      by collected CB TNCs and UA pH in vaginal deliveries (R(2) = 0.53), in contrast
      with TNCs, PW, and BW in C-sections (R(2) = 0.37). TCD34+ cells were predicted by
      adding UA pH (vaginal deliveries, R(2) = 0.75) or PW (C-sections, R(2) = 0.36) to
      collected CB TNCs. CONCLUSIONS: Stress-related perinatal factors, particularly UA
      pH, are associated with CB unit HPCs and may improve unit selection. Multiple
      linear regression models may prove useful for predicting HPCs. Mode of delivery
      affects model choice; UA pH has a strong effect on HPCs in vaginal deliveries.

PMID- 20042030
TI  - Increasing the economic efficacy of peripheral blood progenitor cell collections
      by monitoring peripheral blood CD34+ concentrations.
AB  - BACKGROUND: After mobilization, the collection of peripheral blood progenitor
      cells (PBPCs) can either be started a fixed number of days after having passed
      the white blood cell nadir (fixed-day scheme) or be based on monitoring of CD34+
      cells. This study was conducted to compare both approaches and to assess possible
      financial consequences. STUDY DESIGN AND METHODS: For 29 patients daily
      enumeration of CD34+ cells was used to guide leukapheresis timing. In a
      retrospective analysis for the same group of patients, application of a fixed-day
      scheme was assumed. For scenarios of beginning apheresis 2, 3, 4, or 5 days after
      WBC nadir, the number of apheresis days and granulocyte-colony-stimulating factor
      (G-CSF) application days that could be saved was calculated. RESULTS: A total of
      44 apheresis procedures were performed resulting in a mean CD34+ cell content per
      apheresis product of 10.4 x 10(6) (range, 0.1 x 10(6)-49.5 x 10(6))/kg of body
      weight. The smallest number of deviation days compared to a fixed-day scheme was
      found for beginning an apheresis on Day 3. In comparison to this, CD34+
      monitoring reduced the number of G-CSF days by 9 and the number of apheresis
      procedures by 11 overall, resulting in savings of euro;19,965 (US$28,788) in
      comparison to expenses of euro826 (US$1191) for CD34+ monitoring. CONCLUSIONS:
      Measurement of CD34+ cells has reached a precision enabling a prediction of the
      harvest success. In comparison to a fixed-day scheme, daily CD34+ monitoring
      reduces the donor's exposition to G-CSF, enables collection of a sufficient
      number of PBPCs in the least possible number of apheresis sessions, and improves
      the economic efficacy of the institution.

PMID- 20042031
TI  - Meta-analysis of clinical studies of the purported deleterious effects of "old"
      (versus "fresh") red blood cells: are we at equipoise?
AB  - BACKGROUND: A meta-analysis examined whether the available data support an
      adequate suspicion that transfusion of old red blood cells (RBCs) is associated
      with increased mortality, organ failure, infection, prolonged mechanical
      ventilation, and prolonged stay in the hospital or the intensive care unit. Such
      suspicion is required for intentionally exposing patients enrolled in randomized
      controlled trials (RCTs) to the known or probable--but rare--risks of old RBCs,
      to document (and prevent) purported common adverse effects of old RBCs. STUDY
      DESIGN AND METHODS: Observational studies presenting adjusted results were
      eligible for analysis if the adequacy of the adjustment for confounding factors
      could be assessed. Three RCTs and 24 observational studies were retrieved.
      Medically and statistically homogeneous studies were integrated by fixed-effects
      methods. Otherwise homogeneous studies conducted in different clinical settings
      were integrated by random-effects methods. RESULTS: Based on "as-treated"
      analysis, transfusion of old RBCs was associated with a significant reduction in
      mortality (summary odds ratio, 0.38; 95% confidence interval, 0.14-0.99; p <
      0.05) across two small RCTs. Integration of adjusted findings on the same
      outcome, from observational studies conducted in the same setting, produced
      summary results that were either negative (in six analyses) or impossible to
      evaluate owing to uncontrolled confounding by the number of transfused RBCs (in
      two analyses). CONCLUSION: The available data do not support an adequate
      suspicion that old RBCs may be associated with common adverse morbidity and/or
      mortality outcomes, so as to justify exposing experimental subjects to the other
      known or probable--but rare--risks of old RBCs.

PMID- 20042032
TI  - Generation of histo-blood group B transferase by replacing the N-acetyl-D
      galactosamine recognition domain of human A transferase with the galactose
      recognition domain of evolutionarily related murine alpha1,3
      galactosyltransferase.
AB  - BACKGROUND: The alpha1,3-galactosyl epitope (alpha1-3Gal epitope), a major
      xenotransplant antigen, is synthesized by alpha1,3-galactosyltransferase (alpha1
      3Gal transferase), which is evolutionarily related to the histo-blood group A/B
      transferases. STUDY DESIGN AND METHODS: We constructed structural chimeras
      between the human type A and murine alpha1-3Gal transferases and examined their
      activity and specificity. RESULTS: In many instances, a total loss of transferase
      activity was observed. Certain areas could be exchanged, with a potential
      diminishing of activity. With a few constructs, changes in acceptor substrate
      specificity were suspected. Unexpectedly, a functional conversion from A to B
      transferase activity was observed after replacing the short sequence of human A
      transferase with the corresponding sequence from murine alpha1-3Gal transferase.
      CONCLUSION: Because these two paralogous enzymes differ in 16 positions of the 38
      amino acid residues in the replaced region, our finding may suggest that despite
      separate evolution and diversified acceptors, these glycosyltransferases still
      share the three-dimensional domain structure that is responsible for their sugar
      specificity, arguing against the functional requirement of a strong purifying
      selection playing a role in the evolution of the ABO family of genes.

PMID- 20042034
TI  - Scanning electron microscopy and fungal culture of hoof horn from horses
      suffering from onychomycosis.
AB  - Horn samples were taken from the hooves of eight horses with clinical signs of
      equine onychomycosis in at least one hoof capsule. None of the horses had a
      documented mycological history. The predominant alterations of the horn capsules
      were sand cracks, white line disease, brittleness (especially around the nail
      holes), parakeratosis and bruising. The horn samples were stored in sterile tubes
      for transportation and transferred onto Sabouraud Dextrose Agar and dermatophyte
      test agar for mycological examination within 6 h. Fungal cultures were incubated
      for 30 days at room temperature. Fungal identification was based on colonial
      morphology and microscopic examination of conidia. Horn samples were also stored
      at -80 degrees C until used for scanning electron microscopy (SEM). The fungal
      culture revealed that the hoof horn from all eight horses was infected with
      keratinophilic fungi. The keratinopathogenic fungi Trichophyton spp and
      Scopulariopsis brevicaulis were also detected in six horses. SEM revealed severe
      alterations of the horn structure in horn samples infected with
      keratinopathogenic fungi compared to horn samples from a sound hoof. The most
      evident changes were deterioration of the tubular structure of the horn wall,
      disruption of the horny layers, superficial lysis of cornified cells and the
      presence of fungal elements. Samples without dermatophyte or Scopulariopsis
      infection, in contrast, were similar to healthy hoof horn.

PMID- 20042036
TI  - Species distribution and antimicrobial susceptibility of staphylococci isolated
      from canine otitis externa.
AB  - The diversity of species of the genus Staphylococcus sp. and the antimicrobial
      resistance of isolates from 151 unmedicated dogs of both sexes with a clinical
      diagnosis of otitis were recorded. Ninety-one isolates of Staphylococcus spp.
      were identified by biochemical reactions and tested for susceptibility to 15
      antimicrobials. Coagulase-positive species were most common; S. pseudintermedius
      (38.4%), S. schleiferi schleiferi (15.4%), S. aureus (14.3%), S. epidermidis
      (11%), S. simulans (11%), S. schleiferi coagulans (8.8%) and S. saprophyticus
      (1.1%). All the isolates showed resistance to at least one drug and 89% were
      multiresistant. Amoxicillin combined with clavulanic acid and oxacillin were the
      most effective, while resistance was widely observed for neomycin and
      erythromycin. The results highlight the recognition and the potential need for
      bacterial culture with species identification and antimicrobial susceptibility
      tests for appropriate antimicrobial therapy.

PMID- 20042037
TI  - Mapping of the dog skin based on biophysical measurements.
AB  - Trans epidermal water loss (TEWL), skin hydration status and pH were determined
      in 14 skin regions of five healthy male Beagle dogs (2-4 years) both before and
      after anaesthesia. Trans epidermal water loss was highest for the footpad and
      head and lowest for the inguinal region. Skin hydration status was higher in the
      ear but did not vary significantly in other regions. Skin pH was usually alkaline
      with the highest values on the lower back and tail. Following anaesthesia, TEWL
      and skin hydration were significantly lower on the head, upper back and footpad,
      and upper back and elbow respectively, while skin pH was unaffected by this
      procedure. While measurement of pH would seem to be valid anywhere on the body in
      anaesthetized dogs, regional factors should be considered when interpreting TEWL
      and skin hydration values and when treating regional skin diseases in veterinary
      practice.

PMID- 20042038
TI  - Canine inverted papillomas associated with DNA of four different
      papillomaviruses.
AB  - Inverted papillomas are uncommon papillomavirus (PV)-induced canine skin lesions.
      They consist of cup- to dome-shaped dermal nodules with a central pore filled
      with keratin. Histologically they are characterized by endophytic projections of
      the epidermis extending into dermis. Cytopathic effects of PVs infection include
      the presence of clumped keratohyalin granules, koilocytes and intranuclear
      inclusion bodies. Different DNA hybridization studies carried out with a canine
      oral papillomavirus (COPV) probe suggested that a different PV than COPV might
      cause these lesions. Canine papillomavirus 2 (CPV2) was discovered a few years
      ago in inverted papillomas of immunosuppressed beagles. Two other cases,
      presenting with distinct clinical and histological features have also been
      described. This study was carried out on four dogs with clinical and histological
      signs of inverted papillomas. Molecular biological analyses confirmed that PV DNA
      was present in all four lesions but demonstrated that the sequences in each case
      were different. One corresponded to COPV, the second to CPV2, and the third and
      fourth to unknown PVs. These findings suggest that inverted papillomas are not
      caused by one single PV type. Similar observations have also been made in human
      medicine.

PMID- 20042039
TI  - Frequent detection of papillomavirus DNA in clinically normal skin of cats
      infected and noninfected with feline immunodeficiency virus.
AB  - Feline cutaneous squamous cell carcinomas (SCCs) often contain felis domesticus
      papillomavirus type 2 (FdPV-2) DNA. While this may suggest FdPV-2 causes feline
      SCC development, the proportion of cats that are asymptomatically infected by
      this PV is unknown. Infection by feline immunodeficiency virus (FIV) is
      associated with high rates of cutaneous SCC development, possibly due to
      increased PV infection. This study examines the frequency of cutaneous
      asymptomatic FdPV-2 infections in cats and compares the rate of FdPV-2 infection
      in 22 FIV-positive cats with that in 22 FIV-negative cats. FdPV-2 sequences were
      detected in 39% of skin swabs. One or both swabs contained FdPV-2 DNA from 52% of
      the cats. FIV status, age or sex of the cat did not significantly influence FdPV
      2 infection. Cats that shared a household with a PV-infected cat could remain
      uninfected suggesting infection depends more on host factors than exposure to the
      PV. These results indicate that asymptomatic FdPV-2 infections are common in
      cats, but do not provide evidence that FdPV-2 causes feline SCC development.

PMID- 20042040
TI  - Transmission electron microscopy studies in an experimental model of canine
      atopic dermatitis.
AB  - Impairment of skin barrier function has been hypothesized in canine atopic
      dermatitis (AD). In this prospective, controlled study, the ultrastructure of the
      upper epidermal layers was investigated using an experimental model of canine AD.
      Seven atopic Beagles sensitized to Dermatophagoides farinae and four healthy
      Beagles were used as controls. Both normal and atopic dogs were challenged with
      D. farinae for 3 days. Clinical signs were scored and skin biopsies were taken
      from the inguinal area before and 3 days after allergen exposure. Samples were
      processed to enhance lipid visibility and evaluated by Transmission Electron
      Microscopy. Emphasis was placed on evaluation of the lipid lamellae (LL), and
      lamellar bodies (LB) of the stratum corneum.After allergen challenge, atopic
      Beagles developed severe pruritic dermatitis while no skin lesions were noted in
      the controls. Ultrastructurally, before allergen challenge, atopic Beagles
      displayed focally severe abnormalities in LL organization and wider intercellular
      spaces containing abnormal lipid material. In atopic Beagles, LBs were frequently
      found inside corneocytes while this finding was not observed in the controls.
      After allergen challenge, further increase of intercellular spaces was observed
      in the stratum corneum of atopic Beagles while no appreciable changes were
      observed in the normal dogs. Intercellular spaces in atopic Beagles were filled
      with abundant amounts of abnormal lipid material and highly disorganized LL. It
      is concluded that baseline differences in the ultrastructure of the skin exist
      between normal and experimentally sensitized atopic Beagles and that these
      changes are aggravated by allergen challenge and the resulting flare-up of
      dermatitis.

PMID- 20042041
TI  - Nodular granulomatous fungal skin diseases of cats in the United Kingdom: a
      retrospective review.
AB  - IDEXX Laboratories database of cases submitted from the UK between March 2005 and
      February 2008 (36 months) was investigated for feline nodular granulomatous skin
      disease associated with fungal infection. Cytological and/or histological slides
      were reviewed and the diagnosis was based on the microscopic pattern of the
      inflammatory response and morphology of the causative organism. Aetiological
      diagnoses were hyalohyphomycosis (64 of 77 cases), phaeohyphomycosis (five of 77
      cases) and dermatophytic pseudomycetoma (eight of 77 cases). All cases of
      hyalohyphomycosis were suspected to be alternariosis based on common features
      including anatomical distribution of lesions (48 of 64 cases involved the nostril
      and bridge of nose, face and ears), pattern of histological changes, morphology
      of the causative organism and results of fungal culture (Alternaria three of 16
      and 'saprophyte' nine of 16 cases). Cases of phaeohyphomycosis were
      demographically and histologically similar to those of alternariosis, except the
      causative organisms were deeply pigmented brown and had a variety of morphologies
      that were different from Alternaria. Dermatophytic pseudomycetomas had a
      characteristic histological pattern including the presence of fungal
      microcolonies or grains within the tissue. These occurred most often on the trunk
      (five of eight cases) and four of eight cases were in Persian cats. These
      findings indicate that alternariosis is by far the most common nodular fungal
      skin disease of cats in the UK.

PMID- 20042042
TI  - ISBT Guidelines for validation of automated systems in blood establishments.

PMID- 20042043
TI  - Pandemic Swine flu 2009.

PMID- 20042044
TI  - In memoriam - Jonathan S. Allan, DVM (1952-2009).

PMID- 20042046
TI  - Assessment of the potential risk of infection associated with Clostridium
      difficile from porcine xenografts.
AB  - There are numerous concerns over the potential for transfer of pathogens between
      species during clinical xenotransplantation, and although current clinical
      application is limited, porcine xenografts have been previously used to treat
      patients with severe burns. Donor animals providing the xenografts are sourced
      from a healthy commercial herd, however, as pigs are a known source of zoonotic
      agents, a number of diseases are required to be excluded from pigs used for
      xenotransplantation purposes. Many studies have indicated the relevance of viral
      zoonoses, however, little has been done with regard to the potential for transfer
      of pathogens related to health care associated infections. Clostridium difficile
      is a major cause of neonatal enteritis in pigs and an important feature of this
      organism is that pigs can be asymptomatic carriers. This study has examined the
      incidence of C. difficile PCR ribotypes present in healthy donor pigs to
      determine if pig faeces, and in particular, contamination of skin with faecal
      matter, is a potential route for the transfer of C. difficile. Animals were found
      to have human ribotype 017 present in the faecal matter, however, no C. difficile
      was isolated from skin samples taken from the same animals. In addition, due to
      the risk factors associated with C. difficile infection, the antimicrobial
      susceptibility of the C. difficile isolates has been determined.

PMID- 20042047
TI  - Production and characterization of transgenic pigs expressing porcine CTLA4-Ig.
AB  - BACKGROUND: Inhibition of the T-cell-mediated immune response is a necessary
      component of preventing rejection following xenotransplantation with pig alpha1,3
      galactosyltransferase gene-knockout (GTKO) organs. Cytotoxic T lymphocyte
      associated antigen (CTLA4) is a co-stimulatory molecule that inhibits T-cell
      activity and may be useful in prolonging graft rejection. METHODS: An expression
      vector was built containing the extracellular coding region of porcine (p) CTLA4
      fused to the hinge and CH2/CH3 regions of human IgG1 (pCTLA4-Ig). Pigs transgenic
      for pCTLA4-Ig, on either a GTKO or wild-type (WT) genetic background, were
      produced by nuclear transfer and characterized using Western blot analysis,
      immunofluorescence, ELISA, and necropsy. RESULTS: Fifteen pCTLA4-Ig-transgenic
      piglets resulted from five pregnancies produced by nuclear transfer. All
      transgenic pigs exhibited robust expression of the pCTLA4-Ig protein and most
      expressed the transgene in all organs analyzed, with significant levels in the
      blood as well. Despite initial good health, these pigs exhibited diminished
      humoral immunity, and were susceptible to infection, which could be managed for a
      limited time with antibiotics. CONCLUSIONS: Viable pigs exhibiting robust and
      ubiquitous expression of pCTLA4-Ig were produced on both a WT and GTKO
      background. Expression of pCTLA4-Ig resulted in acute susceptibility to
      opportunistic pathogens due at least in part to a significantly compromised
      humoral immune status. As this molecule is known to have immunosuppressive
      activity, high levels of pCTLA4-Ig expression in the blood, as well as defective
      development related to exposure to pCTLA4-Ig in utero, may contribute to this
      reduced immune status. Prophylactic treatment with antibiotics may promote
      survival of disease-free transgenic pigs to a size optimal for organ procurement
      for transplantation. Additional genetic modifications and/or tightly regulated
      expression of pCTLA4Ig may reduce the impact of this transgene on the humoral
      immune system.

PMID- 20042048
TI  - Pigs transgenic for human thrombomodulin have elevated production of activated
      protein C.
AB  - BACKGROUND: The inability of porcine thrombomodulin (TM) to activate human
      anticoagulant protein C after pig-to-human xenotransplantation may lead to an
      aberrant activation of coagulation with microthrombosis and ultimately failure of
      the transplanted organ. Here, we describe the production of triple-transgenic
      pigs expressing hCD59/DAF and human thrombomodulin (hTM) and tested hTM
      transgenic fibroblasts obtained from these pigs for their ability to activate
      human protein C in a new in vitro assay. METHODS: Fibroblast cell cultures were
      established from a hCD59/DAF transgenic pig and transfected with a vector coding
      for hTM under transcriptional control of the CMV promoter. Transfected cells were
      analyzed for integration and expression of the hTM vector by PCR and RT-PCR. One
      cell clone was used as donor for somatic cell nuclear transfer to produce triple
      transgenic (CD59/DAF/hTM) pigs. Pigs were characterized in detail with regard to
      hTM integration and expression by PCR, RT-PCR, Northern blot, Western blot,
      immunostaining, and FACS analysis. Fibroblasts from hTM-transgenic pigs were
      analyzed in a new in vitro hTM coactivity assay to assess the production of
      activated protein C (aPC) and results were compared to those from wild-type
      controls. RESULTS: In total, 1040 cloned transgenic embryos were transferred to
      eight recipients. Five recipients remained pregnant and delivered 22 piglets.
      Expression of hTM was detected in all xenorelavant organs including heart, liver,
      kidney, lung, and pancreas. The lowest levels of expression were found in lung
      and liver while all animals showed a strong, but frequently patchy expression
      pattern of hTM in heart, kidney, and pancreas. The hTM cofactor activity (ranging
      on a scale from 5-18 U/10(5) cells/2h) was significantly higher in fibroblasts of
      hTM-transgenic clones compared to wild-type porcine fibroblasts (1.7 U/10(5)
      cells/2h). CONCLUSIONS: For the first time, healthy hTM-transgenic pigs could be
      successfully generated by somatic cell nuclear transfer. hTM can be expressed in
      porcine organs without perturbation of the porcine coagulation system. hTM
      transgenic porcine fibroblasts showed elevated aPC production in an in vitro hTM
      coactivity assay. These findings warrant further work on the control of the
      xenogenic activation of coagulation by transgenic approaches.

PMID- 20042049
TI  - Reference values of clinical chemistry and hematology parameters in rhesus
      monkeys (Macaca mulatta).
AB  - BACKGROUND: Rhesus monkey models are valuable to the studies of human biology.
      Reference values for clinical chemistry and hematology parameters of rhesus
      monkeys are required for proper data interpretation. METHODS: Whole blood was
      collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex,
      3 to 5 yr old. Routine chemistry and hematology parameters, and some special
      coagulation parameters including thromboelastograph and activities of coagulation
      factors were tested. RESULTS AND CONCLUSION: We presented here the baseline
      values of clinical chemistry and hematology parameters in normal Chinese rhesus
      monkeys. These data may provide valuable information for veterinarians and
      investigators using rhesus monkeys in experimental studies.

PMID- 20042050
TI  - Diabetic rats and mice are resistant to porcine and human insulin: flawed
      experimental models for testing islet xenografts.
AB  - BACKGROUND: Islet transplantation is potentially a promising therapy for the
      restoration of carbohydrate control to diabetic patients. However, the global
      application of islet transplantation requires a ubiquitous source of beta cells.
      The xenotransplantation of porcine islets would provide such a source. Success in
      porcine islet xenografting has been achieved in diabetic primates. However, there
      are few reports of reversal of diabetes with porcine islet xenografts in rodent
      models of diabetes, relative to the number of successful rodent experiments
      performed as allografts. Here we report for the first time the inability of
      porcine (and human) insulin to control blood glucose levels in diabetic rodents
      determined by a series of dose escalating studies. METHODS: Insulin was
      administered intravenously to streptozotocin induced diabetic Lewis rats, Balb/c
      and athymic Balb/c mice (n = 5 per group) at the following doses: Group I
      "physiological dose" (pd) of 0.16 U/kg for a total dose of 40 mU to a 250 g rat.
      Group II received 0.64 U/kg (4xpd), group III 1.6 U/kg (10xpd) and group IV 6.4
      U/kg (40xpd). Blood glucose levels were monitored in each animal at seven time
      points: 0 (pre-injection), 10 min, 20 min, 30 min, 45 min, 1 h, 1.5 h, 2 h and 3
      h post-injection. Serum insulin levels were also determined. RESULTS: Diabetic
      Lewis rats achieved a maximum reduction in blood glucose from 22.1 +/- 1.8mmol/l
      to 8.0 +/- 3.1 mmol/l (a 63.7% reduction), 90 minutes post-injection of 6.4 U/kg
      dose of porcine insulin (40xpd). Human insulin was less effective at reducing
      blood glucose levels in rats than porcine insulin (P < 0.001). Porcine insulin
      reduced blood glucose levels in Balb/c mice from a mean of 18.2 +/- 2.1 mmol/l to
      a hypoglycemic minimum of 1.26 +/- 0.18 mmol/l a reduction of 93.0%, 60 min post
      injection of the maximum dose of 6.4 U/kg. Balb/c mice were significantly more
      responsive to porcine insulin than Lewis rats at doses of 0.64 U/kg (P < 0.001),
      1.6 U/kg (P < 0.05) and 6.4 U/kg (P < 0.001). Athymic Balb/c nude mice reached a
      maximum reduction in blood glucose from 21.6 +/- 1.8 mmol/l to 3.6 +/- 0.9 mmol/l
      (a 83.4% reduction) 120 min post-injection at a dose of 6.4 U/kg. Overall,
      athymic Balb/c nude mice were more resistant to porcine insulin than
      immunocompetent Balb/c mice at doses of 0.64 U/kg (P < 0.001), 1.6 U/kg (P <
      0.001) and 6.4 U/kg (P < 0.05). Insulin diluent alone marginally increased blood
      glucose levels in all animals tested. CONCLUSIONS: Our results suggest that
      restoration of normoglycemia in diabetic rodents is not ideal for testing porcine
      islets xenografts since the reversals of diabetes in these species requires 20 to
      40 times the dose of porcine insulin used in humans.

PMID- 20042052
TI  - Transgenic expression of the human A20 gene in cloned pigs provides protection
      against apoptotic and inflammatory stimuli.
AB  - BACKGROUND: Porcine organs with transgenic expression of anti-apoptotic and anti
      inflammatory genes like the human A20 gene (hA20), a tumor necrosis factor-alpha
      (TNF-alpha)-inducible gene, may control the acute vascular rejection (AVR) of
      porcine xenografts. The human A20 molecule possesses protective features against
      inflammatory and apoptotic stimuli in various cell types including endothelial
      cells, rendering it a promising candidate for transgenic pig production in the
      context of xenotransplantation. Here, we produced pigs transgenic for hA20 and
      investigated whether hA20-transgenic porcine aortic endothelial cells (PAECs)
      were resistant against the induction of apoptosis in vitro and to what extent
      hA20-transgenic porcine hearts were protected against ischemia/reperfusion (I/R)
      injury. METHODS: Porcine fetal fibroblasts (PFFs) were transfected with the
      vector pCAGGSEhA20-IRESNEO containing a chicken beta-actin/rabbit beta-globin
      (CAGGS)-promoter element, known to provide ubiquitous gene expression in both
      mice and pigs. Transfected PFFs were then used in somatic cell nuclear transfer
      (SCNT). Three hA20-transgenic pigs were killed for PAEC isolation and organ mRNA
      and protein expression analysis by reverse transcriptase-polymerase chain
      reaction (RT-PCR), Northern and Western Blotting. PAECs were tested for
      susceptibility to apoptosis after TNF-alpha challenging and triggering of the
      CD95(Fas)/CD95Ligand pathway. Five transgenic and three wild type animals were
      subjected to an I/R experiment followed by measurement of infarct size,
      myeloperoxidase (MPO) activity and subendocardial segmental shortening (SES) to
      assess protective effects of hA20 in the porcine myocardium. RESULTS: The hA20
      transgenic pigs developed normally and expression of hA20 was found in skeletal
      muscle, heart and PAECs. Cultured human A20-transgenic PAECs showed significantly
      reduced apoptosis when compared to their wild type counterparts and were less
      susceptible to the induction of cell death by CD95(Fas)L. Only partial protection
      of hA20-transgenic pig hearts was observed after I/R. While infarct size did not
      differ between the two groups after ischemic assault, hA20-transgenic porcine
      hearts showed significantly lower MPO activity and better hemodynamic performance
      (determined as SES) than their wild type counterparts. CONCLUSIONS: The hA20 gene
      was for the first time functionally expressed in transgenic pigs. Although the
      CAGGS is a ubiquitous promoter element, expression was restricted to heart,
      skeletal muscle and PAECs of transgenic animals. Cultivated hA20-transgenic PAECs
      were protected against TNF-alpha-mediated apoptosis, and partially protected
      against CD95(Fas)L-mediated cell death; cardiomyocytes were partially protected
      in I/R. These findings reveal hA20 as a promising molecule for controlling AVR in
      multi-transgenic pigs for xenotransplantation studies.

PMID- 20042051
TI  - Successful cross-breeding of cloned pigs expressing endo-beta-galactosidase C and
      human decay accelerating factor.
AB  - BACKGROUND: For successful organ xenotransplantation, genetically engineered pigs
      have been actively produced. Our attention has focused on (i) reduction of
      alphaGal expression by its digestion enzyme, endo-beta-galactosidase C
      (EndoGalC), and (ii) inhibition of complement activation by human decay
      accelerating factor (hDAF). Cell sorting and nuclear transfer enabled the
      effective production of cloned pigs expressing transgene at high levels. We
      report the successful cross-breeding of pigs expressing EndoGalC and hDAF.
      METHODS: After hDAF and EndoGalC genes were transfected into pig fibroblasts from
      the fetus of Landrace x Yorkshire and Meishan, respectively, transfected cells
      expressing transgenes effectively were collected using a cell sorter. Cloned pigs
      were produced using the technology of somatic cell nuclear transfer. After cross
      breeding of cloned pigs, kidneys expressing both EndoGalC and hDAF were
      transplanted into baboons to examine the efficacy of gene transduction. RESULTS:
      Well-designed cloned pigs were produced by cross-breeding. alphaGal expression
      levels in cloned pigs were reduced up to 2 to 14%, compared to that in wild-type
      pigs. hDAF expression reached about 10- to 70-fold, compared to that in human
      umbilical vein endothelial cells. No congenital deformity was observed. There was
      no problem of increased stillbirth rate or growth retardation. Hyperacute
      rejection could be avoided in such a cloned pig to baboon kidney transplantation
      without any treatment for anti-pig antibody removal. However, grafts suffered
      from fibrin deposition as early as 1 h after transplantation, and were rejected
      after 1 week. CONCLUSIONS: Using a cell sorting system for effective collection
      of transfected cells, two types of cloned pigs were produced with a very high
      level of hDAF expression and a low level of alphaGal expression. Such genetic
      modification was effective in preventing hyperacute rejection, but there was an
      immediate lapse into procoagulation after transplantation, resulting in acute
      vascular rejection. Effective suppression of antibody binding to the graft would
      be necessary, even if a high level of hDAF is expressed.

PMID- 20042053
TI  - Monitoring of porcine and baboon cytomegalovirus infection in
      xenotransplantation.

PMID- 20042055
TI  - Xenotransplantation literature update: May-October, 2009.

PMID- 20042057
TI  - Vaccination of poultry workers: delivery and uptake of seasonal influenza
      immunization.
AB  - Avian influenza is a highly infectious disease in poultry and although the risk
      of human infection is low, concerns exist that it could evolve into a new human
      strain of pandemic potential if reassortment with a human influenza virus occurs.
      In January 2007, the UK government introduced a programme to vaccinate poultry
      workers to reduce the potential of such an event. This study evaluates the
      delivery, uptake and costs of the programme in three counties of England. A
      questionnaire survey was completed by consultants in public health in all the
      Primary Care Trusts in Norfolk, Suffolk and Cambridgeshire in May 2007. The
      delivery of the programme varied between Primary Care Trusts, including being
      delivered in some cases by clinics in primary care, by general practitioners and
      occupational health services in others. The uptake of vaccination was low ranging
      from 7% to 29% at a cost of L29 to L132 per person vaccinated. Vaccination of
      poultry workers as a public health measure to prevent an influenza pandemic is
      likely to be ineffective with the level of coverage found in this evaluation in
      our region.

PMID- 20042058
TI  - Zoonotic infections of buffalopox in India.
AB  - Four outbreaks of buffalopox in domestic buffaloes, with considerable mortality
      with high case fatality rates in young buffalo calves and high morbidity with
      significant productivity loss in terms of reduction in milk yield in adult
      animals along with severe zoonotic infection in milk attendants were recorded at
      various places in India, during 2006-2008. In buffaloes, the pox lesions were
      confined to udder and teats of the majority of the affected animals, and in few
      animals the lesions were appeared on the hindquarters, indicating generalized
      infection. The overall disease morbidity, mortality and case fatality rate were
      6.8%, 0.7% and 11.4% respectively. Milkers developed pox-like lesions on the
      hands, forearms and forehead accompanied by fever, axillary lymphadenopathy and
      general malaise. The causative agent of the outbreaks, buffalopox virus (BPXV),
      was confirmed upon virus isolation in cell culture, electron microscopy, A-type
      inclusion (ATI) and ankyrin repeat protein (C18L) gene-specific polymerase chain
      reactions (PCR). Further, sequence analysis of the BPXV isolates from human and
      buffalo showed more identity of ATI and C18L genes sequences with that of other
      orthopoxviruses at nucleotide and amino acid levels and confirmed a close
      relationship of BPXV with Vaccinia virus (VACV) or VACV-like viruses. Considering
      the zoonotic impact and productivity losses of buffalopox infection, the control
      measures are imperative in curtailing economic and public health impact of the
      disease.

PMID- 20042059
TI  - Livestock associated methicillin-resistant Staphylococcus aureus (LaMRSA)
      isolated from lesions of pigs at necropsy in northwest Germany between 2004 and
      2007.
AB  - An increasing number of reported detections of methicillin-resistant
      Staphylococcus aureus (MRSA) in food animals since 2007 has led to the assumption
      that there is an emerging zoonotic problem with livestock associated (la)MRSA
      potentially aggravating the MRSA problem in humans. It was the objective of the
      study to investigate, whether MRSA was present in clinical specimens of pigs
      collected at post-mortem since 2004 and to further characterize these isolates.
      We studied 138 isolates of S. aureus collected between 2004 and 2007 from various
      pathological lesions of pigs at necropsy. Potential MRSA were identified by
      growth on selective chromogenic media. Isolates were confirmed as MRSA using
      multiplex PCR. Confirmed isolates were spa- and SCCmec-typed and were tested for
      antimicrobial resistance. Overall, 60 (43%) S. aureus isolates were identified as
      MRSA. The majority (57/60) of the MRSA isolates found in the altered porcine
      tissues were spa-types associated with MRSA ST398. Three MRSA were ST97 isolates,
      a type that has not been described as an MRSA in pigs before. Other clonal
      complexes (ST9, ST30) dominated among the methicillin-sensitive S. aureus. MRSA
      were found in similar frequency in all 4 years. We assume that MRSA in pigs may
      have occurred earlier than 2004 and might be not really 'emerging', but rather
      have been overlooked until recently. The potentially causative role of the MRSA
      in the lesions warrants further investigation.

PMID- 20042060
TI  - Sushi in pregnancy, parasitic diseases - obstetrician survey.
AB  - Parasites from raw fish can lead to a wide range of clinical manifestations and
      can be challenging to treat in pregnancy as result of medication exposure of the
      foetus. We surveyed obstetrician-gynecologists (ob-gyns) in the U.S. to determine
      their knowledge about the consumption of raw fish during pregnancy. In March
      2007, a questionnaire was mailed to members of the American College of
      Obstetricians and Gynecologists (ACOG) randomly selected to represent all
      members. Non-responding physicians were sent two additional mailings. Of the 606
      ACOG members surveyed, 305 (50%) responded. Most (82%) respondents indicated that
      eating raw fish is not safe during pregnancy. However, few (19%) knew that
      thorough freezing kills parasites in fish. Nearly all (94%) respondents thought
      that parasitic infections can be more challenging to treat in pregnancy. U.S. ob
      gyns believe that eating raw fish during pregnancy is not safe; most would
      benefit from information about how to prevent infection and about treatment.

PMID- 20042061
TI  - The European rabbit (Oryctolagus cuniculus), a source of zoonotic
      cryptosporidiosis.
AB  - Cryptosporidium spp. have been found in the faeces of over 150 mammalian host
      species, but the risks to public health from wildlife are poorly understood. In
      summer 2008, the Cryptosporidium sp. rabbit genotype was identified as the
      aetiological agent in an outbreak of waterborne human cryptosporidiosis. The
      source was a wild rabbit that had entered a treated water tank. To establish
      current knowledge about Cryptosporidium spp. infecting lagomorphs, especially the
      host range and biological characteristics of the rabbit genotype, and the
      potential risks to public health that rabbits may pose in the transmission of
      zoonotic cryptosporidiosis, we undertook a literature and data review. The
      literature returned demonstrates that although the European rabbit (Oryctolagus
      cuniculus) has been the most widely studied lagomorph, few large scale studies
      were found. The prevalence of Cryptosporidium spp. in wild rabbit populations in
      the two large scale studies was 0.9% (95%CI 0.2-5.0) and 0.0% (95%CI 0.0-1.6).
      Neither study provided age nor sex profiles nor typing of Cryptosporidium
      isolates. The infecting Cryptosporidium species was confirmed in just four other
      studies of rabbits, all of which showed the rabbit genotype. Human-infectious
      Cryptosporidium species including Cryptosporidium parvum have caused experimental
      infections in rabbits and it is likely that this may also occur naturally. No
      published studies of the host range and biological features of the
      Cryptosporidium rabbit genotype were identified, but information was generated on
      the identification and differentiation of the rabbit genotype at various genetic
      loci. Both pet and wild rabbits are a potential source of human cryptosporidiosis
      and as such, good hygiene practices are recommended during and after handling
      rabbits or exposure to their faeces, or potentially contaminated surfaces. Water
      supplies should be protected against access by wildlife, including rabbits.

PMID- 20042062
TI  - Antimicrobial resistance of enterococci isolated from mastitic bovine milk
      samples in Korea.
AB  - The aim of this study was to determine the antimicrobial resistance of various
      species of enterococci isolated from mastitic bovine milk samples. A total of 105
      enterococci isolates were examined: Enterococcus faecalis (n = 47), Enterococcus
      faecium (n = 39), Enterococcus gallinarum (n = 6), Enterococcus avium (n = 6),
      Enterococcus hirae (n = 5) and Enterococcus durans (n = 2). All the isolates were
      susceptible to ampicillin, gentamicin and vancomycin, and only a single E. hirae
      isolate was resistant to ampicillin. In general, the most frequently observed
      resistance among the enterococcal isolates was to tetracycline (69.5%), followed
      by penicillin (64.7%), erythromycin (57.1%) and cephalothin (44.7%). A similar
      antimicrobial resistance pattern was observed among individual species except E.
      durans, which exhibited only tetracycline resistance. Resistance observed among
      isolates of E. hirae and E. gallinarum was almost as high as E. faecium and E.
      faecalis. Of 105 isolates, only six (5.7%) strains of E. faecium were susceptible
      to all the antimicrobials tested and about 52% (55/105) showed resistance to more
      than three antimicrobials. The most common multiple resistance pattern was
      penicillin, tetracycline and erythromycin, which was observed in 32 of 105
      (30.4%) isolates. This study demonstrates that enterococcal isolates belonging to
      minor species showed antimicrobial resistance rates as high as those of E.
      faecium and E. faecalis, and that monitoring of antimicrobial resistance should
      not be restricted only to those two major species.

PMID- 20042063
TI  - Evaluation of mass vaccination campaign coverage against rabies in dogs in
      Tunisia.
AB  - In Tunisia, rabies continues to be considered as a serious public health concern.
      Very costly mass vaccination of dogs against rabies and expensive post-exposure
      prophylaxis are prerequisites to maintain a low level of human rabies cases. In
      Tunisia, the implementation of mass vaccination campaigns at the national level
      has undoubtedly contributed to the drop of rabies endemicity, but the overall
      outcome is rather suboptimal. In this investigation, we wanted to estimate the
      extent of the vaccination coverage in dogs in three Governorates (Manouba,
      Kassrine and Mednine), by collecting data through questionnaires and interviews
      relevant to 1470 owned dogs. When the campaign is correctly applied, as in
      Manouba, almost all the targeted dog population can be reached by parenteral
      vaccination and an almost elimination of the disease can be evidenced. However,
      in Kasserine and especially in Medenine, where the vaccination coverage is lower
      than 31%, a reservoir for the disease can be maintained. To match the official
      figures of vaccination coverage, we should update the statistics of the size of
      dog population which seems to be bigger than what is assumed. In addition, we
      wanted to assess the level of involvement of the local population with the
      vaccination campaigns by marking vaccinated dogs with necklaces and establishing
      later on the vaccination coverage accordingly. The highest levels of vaccination
      coverage can be reached in the rural regions. Therefore, the low vaccination
      coverage in rural areas, reported at the national level, is more attributable to
      the lack of human and financial resources to reach remote regions. We think that
      rabies control programmes in Tunisia can be successful if vaccination coverage
      can reach 70% in all parts of the country. The achieved vaccination coverage
      should be estimated after random visits in many parts of the country and by
      checking valid vaccination certificates.

PMID- 20042064
TI  - Salmonella serovars and antimicrobial resistance profiles in beef cattle,
      slaughterhouse personnel and slaughterhouse environment in ethiopia.
AB  - The present study was undertaken to determine the occurrence, distribution and
      antimicrobial resistance profiles of Salmonella serovars in slaughter beef
      cattle, slaughterhouse environment and personnel engaged in flaying and
      evisceration during slaughtering process. A total of 800 samples (each sample
      type, n = 100) consisting of swabs from hides, slaughterhouse personnel hands at
      flaying and evisceration, rumen and caecal contents, mesenteric lymph nodes,
      carcasses and holding pens were collected. Of the total 100 beef cattle examined,
      14% were Salmonella positive in caecal content and/or mesenteric lymph nodes. Of
      the various samples analysed, Salmonella was detected in 31% of hides, 19% of
      rumen contents, 8% of mesenteric lymph nodes, 6% of caecal contents, 2% of
      carcass swabs, 9% of palm swabs taken from the hands of personnel in the
      slaughterhouse during flaying (7%) and evisceration (2%), and in 12% of holding
      pen swabs. The Salmonella isolates (n = 87) belonged to eight different serovars
      of which S. Anatum (n = 54) and S. Newport (19) were the major serovars and both
      serovars were detected in all sample sources except in carcass swabs. Eighteen of
      the 87 (20.7%) Salmonella serovars consisting of Newport (n = 14), Anatum (n = 3)
      and Eastbourne (n = 1) were resistant to one or more antimicrobials. Among the
      antimicrobial resistant Salmonella serovars, S. Newport was multidrug resistant
      (15.6%) and exhibited resistance to streptomycin, sulphisoxazole and
      tetracycline.

PMID- 20042065
TI  - Genotyping of Giardia duodenalis among children and dogs in a closed socially
      deprived community from Italy.
AB  - Molecular characterization of Giardia duodenalis cysts from humans and animals
      living in well-defined contexts is useful to study the circulation of isolates
      and represents a tool to evaluate zoonotic infection risk. The presence of
      giardiasis in children living in a disadvantaged and socially deprived small Rom
      community, as well in dogs roaming freely in the same context was carried out by
      microscopic analysis and beta-giardin gene amplification. Five out of 14 children
      were found positive at microscopic examination for G. duodenalis and six positive
      at PCR, while eight out of 14 dogs tested both microscopically and molecularly
      positive for G. duodenalis. Moreover, most of the children and dogs were
      symptomatic. Molecular characterization of Giardia positive samples from children
      and dogs showed 99.5% identity with Giardia Assemblage A1. The dog-specific
      genotypes C and D were not found. The findings of this survey provide the first
      European evidence to support the possible role of dogs in zoonotic transmission
      involving children and stray dogs in a closed context with very low standards of
      hygiene (i.e. Rom community), and these results show the need to monitor the
      health of marginal populations to safeguard ethnic minority groups.

PMID- 20042066
TI  - West Nile virus transmission in 2008 in north-eastern Italy.
AB  - After 10 years, West Nile virus (WNV) re-emerged in Italy in August 2008. As on
      31 December 2008, the infection affected eight Provinces in three Regions (Emilia
      Romagna, Veneto, Lombardy), where a total of 794 cases of WNV infection in 251
      equine stables were detected on the basis of the clinical signs and as a result
      of a serological screening in horses living in the area. Only 4.0% (32/794) of
      the serologically positive animals showed clinical signs, and the 32 clinical
      cases were reported in 18 different farms. The observed case-fatality rate was
      15.6% (5/32). The confirmed clinical cases were detected from end August to mid
      October. Significant levels of positivity by RT-PCR were also observed in magpies
      (Pica pica) (9.1%, 95% confidence levels: 6.1-13.4%), carrion crows (Corvus
      corone) (7.4%, 95% confidence levels: 3.6-14.4%) and rock pigeons (Columba livia)
      (12.9%, 95% confidence levels: 7.6-21.2%).

PMID- 20042067
TI  - Methicillin-resistant Staphylococcus aureus in resident animals of a long-term
      care facility.
AB  - Animals provide benefits to elderly and chronically ill people by decreasing
      loneliness, increasing social interactions, and improving mental health. As a
      result, many hospitals and long-term care facilities allow family pets to visit
      ill or convalescing patients or support animal-assisted therapy programs. These
      include programs that have resident animals in long-term care facilities. Despite
      the benefits, there are concerns about disease transmission between pets and
      patients. Antibiotic-resistant bacteria, such as methicillin-resistant
      Staphylococcus aureus (MRSA), are a recognized problem in healthcare settings
      leading to refractory infections and potentially life-threatening illnesses. MRSA
      has been isolated from numerous animal species, yet few studies are available on
      the carriage of this pathogen in animals residing in long-term care facilities.
      Our objective was to characterize MRSA carriage among resident animals in a long
      term care facility. METHODS: To document MRSA colonization, nasal swabs from 12
      resident animals (one dogs and 11 cats) of a long-term care facility were
      collected weekly for 8 weeks. Staphylococcus isolates were characterized by
      antimicrobial susceptibility and MRSA isolates were further characterized by
      pulsed-field gel electrophoresis (PFGE). PFGE isolate patterns were compared with
      an existing database of MRSA isolate patterns at the Minnesota Department of
      Health. RESULTS: Two of 11 cats were colonized with MRSA. MRSA was recovered from
      five of eight weekly samples in one cat and two of eight weekly samples in the
      other cat. All isolates were classified as USA100 (healthcare-associated
      strains). DISCUSSION: Long-term care resident animals may acquire MRSA. Clonally
      related strains were identified over the 8-week sampling period. It is unclear if
      pets serve as an on-going source of infection to their human companions in long
      term care facilities.

PMID- 20042068
TI  - Virological surveillance and preliminary antigenic characterization of influenza
      viruses in pigs in five European countries from 2006 to 2008.
AB  - This study presents the results of the virological surveillance for swine
      influenza viruses (SIVs) in Belgium, UK, Italy, France and Spain from 2006 to
      2008. Our major aims were to clarify the occurrence of the three SIV subtypes -
      H1N1, H3N2 and H1N2 - at regional levels, to identify novel reassortant viruses
      and to antigenically compare SIVs with human H1N1 and H3N2 influenza viruses.
      Lung tissue and/or nasal swabs from outbreaks of acute respiratory disease in
      pigs were investigated by virus isolation. The hemagglutinin (HA) and
      neuraminidase (NA) subtypes were determined using standard methods. Of the total
      169 viruses, 81 were classified as 'avian-like' H1N1, 36 as human-like H3N2 and
      47 as human-like H1N2. Only five novel reassortant viruses were identified: two
      H1N1 viruses had a human-like HA and three H1N2 viruses an avian-like HA. All
      three SIV subtypes were detected in Belgium, Italy and Spain, while only H1N1 and
      H1N2 viruses were found in UK and Northwestern France. Cross-hemagglutination
      inhibition (HI) tests with hyperimmune sera against selected older and recent
      human influenza viruses showed a strong antigenic relationship between human H1N1
      and H3N2 viruses from the 1980s and H1N2 and H3N2 human-like SIVs, confirming
      their common origin. However, antisera against human viruses isolated during the
      last decade did not react with currently circulating H1 or H3 SIVs, suggesting
      that especially young people may be, to some degree, susceptible to SIV
      infections.

PMID- 20042069
TI  - Evidence of exposure to spotted fever group rickettsiae among Arizona dogs
      outside a previously documented outbreak area.
AB  - Since 2003, two communities in eastern Arizona have experienced a sustained
      outbreak of Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii,
      associated with transmission by Rhipicephalus sanguineus, the brown dog tick; 70
      human cases, including eight deaths, were reported from these communities during
      2003 through 2008. In both of the affected communities, antibodies to spotted
      fever group rickettsiae (SFGR) were present in dogs before the notice of the
      first human cases, suggesting that dogs may serve as useful sentinels for human
      risk of RMSF in this region. During 2005 and 2006, an exploratory serosurvey was
      conducted among stray and relinquished dogs presenting to animal control
      facilities in eastern Arizona located outside the area where human cases had been
      reported. Antibodies to SFGR were detected in 5.7% (14 of 247) dogs assessed
      outside the RMSF outbreak area. Animal shelters located in counties that either
      included or shared large borders with the outbreak area were significantly more
      likely to have seropositive dogs than facilities in more geographically separated
      counties (P = 0.01). In addition, stray dogs were significantly more likely to be
      antibody-positive than relinquished animals (P = 0.01), suggesting that control
      of stray dog populations should be considered as a means of limiting SFGR
      transmission in this region. The findings from this study may be extrapolated to
      suggest that the current risk for human RMSF infection may extend beyond the
      noted outbreak area. Heightened surveillance for human disease is needed in the
      region.

PMID- 20042070
TI  - Effectiveness of electronic guideline-based implementation systems in ambulatory
      care settings - a systematic review.
AB  - BACKGROUND: Electronic guideline-based decision support systems have been
      suggested to successfully deliver the knowledge embedded in clinical practice
      guidelines. A number of studies have already shown positive findings for decision
      support systems such as drug-dosing systems and computer-generated reminder
      systems for preventive care services. METHODS: A systematic literature search
      (1990 to December 2008) of the English literature indexed in the Medline
      database, Embase, the Cochrane Central Register of Controlled Trials, and CRD
      (DARE, HTA and NHS EED databases) was conducted to identify evaluation studies of
      electronic multi-step guideline implementation systems in ambulatory care
      settings. Important inclusion criterions were the multidimensionality of the
      guideline (the guideline needed to consist of several aspects or steps) and real
      time interaction with the system during consultation. Clinical decision support
      systems such as one-time reminders for preventive care for which positive
      findings were shown in earlier reviews were excluded. Two comparisons were
      considered: electronic multidimensional guidelines versus usual care (comparison
      one) and electronic multidimensional guidelines versus other guideline
      implementation methods (comparison two). RESULTS: Twenty-seven publications were
      selected for analysis in this systematic review. Most designs were cluster
      randomized controlled trials investigating process outcomes more than patient
      outcomes. With success defined as at least 50% of the outcome variables being
      significant, none of the studies were successful in improving patient outcomes.
      Only seven of seventeen studies that investigated process outcomes showed
      improvements in process of care variables compared with the usual care group
      (comparison one). No incremental effect of the electronic implementation over the
      distribution of paper versions of the guideline was found, neither for the
      patient outcomes nor for the process outcomes (comparison two). CONCLUSIONS:
      There is little evidence at the moment for the effectiveness of an increasingly
      used and commercialized instrument such as electronic multidimensional
      guidelines. After more than a decade of development of numerous electronic
      systems, research on the most effective implementation strategy for this kind of
      guideline-based decision support systems is still lacking. This conclusion
      implies a considerable risk towards inappropriate investments in ineffective
      implementation interventions and in suboptimal care.

PMID- 20042071
TI  - Achieving high coverage of larval-stage mosquito surveillance: challenges for a
      community-based mosquito control programme in urban Dar es Salaam, Tanzania.
AB  - BACKGROUND: Preventing malaria by controlling mosquitoes in their larval stages
      requires regular sensitive monitoring of vector populations and intervention
      coverage. The study assessed the effectiveness of operational, community-based
      larval habitat surveillance systems within the Urban Malaria Control Programme
      (UMCP) in urban Dar es Salaam, Tanzania. METHODS: Cross-sectional surveys were
      carried out to assess the ability of community-owned resource persons (CORPs) to
      detect mosquito breeding sites and larvae in areas with and without larviciding.
      Potential environmental and programmatic determinants of habitat detection
      coverage and detection sensitivity of mosquito larvae were recorded during guided
      walks with 64 different CORPs to assess the accuracy of data each had collected
      the previous day. RESULTS: CORPs reported the presence of 66.2% of all aquatic
      habitats (1,963/2,965), but only detected Anopheles larvae in 12.6% (29/230) of
      habitats that contained them. Detection sensitivity was particularly low for late
      stage Anopheles (2.7%, 3/111), the most direct programmatic indicator of malaria
      vector productivity. Whether a CORP found a wet habitat or not was associated
      with his/her unfamiliarity with the area (Odds Ratio (OR) [95% confidence
      interval (CI)] = 0.16 [0.130, 0.203], P < 0.001), the habitat type (P < 0.001) or
      a fence around the compound (OR [95%CI] = 0.50 [0.386, 0.646], P < 0.001). The
      majority of mosquito larvae (Anophelines 57.8% (133/230) and Culicines 55.9%
      (461/825) were not reported because their habitats were not found. The only
      factor affecting detection of Anopheline larvae in habitats that were reported by
      CORPs was larviciding, which reduced sensitivity (OR [95%CI] = 0.37 [0.142,
      0.965], P = 0.042). CONCLUSIONS: Accessibility of habitats in urban settings
      presents a major challenge because the majority of compounds are fenced for
      security reasons. Furthermore, CORPs under-reported larvae especially where
      larvicides were applied. This UMCP system for larval surveillance in cities must
      be urgently revised to improve access to enclosed compounds and the sensitivity
      with which habitats are searched for larvae.

PMID- 20042072
TI  - Transcriptional adaptations following exercise in thoroughbred horse skeletal
      muscle highlights molecular mechanisms that lead to muscle hypertrophy.
AB  - BACKGROUND: Selection for exercise-adapted phenotypes in the Thoroughbred
      racehorse has provided a valuable model system to understand molecular responses
      to exercise in skeletal muscle. Exercise stimulates immediate early molecular
      responses as well as delayed responses during recovery, resulting in a return to
      homeostasis and enabling long term adaptation. Global mRNA expression during the
      immediate-response period has not previously been reported in skeletal muscle
      following exercise in any species. Also, global gene expression changes in equine
      skeletal muscle following exercise have not been reported. Therefore, to identify
      novel genes and key regulatory pathways responsible for exercise adaptation we
      have used equine-specific cDNA microarrays to examine global mRNA expression in
      skeletal muscle from a cohort of Thoroughbred horses (n = 8) at three time points
      (before exercise, immediately post-exercise, and four hours post-exercise)
      following a single bout of treadmill exercise. RESULTS: Skeletal muscle biopsies
      were taken from the gluteus medius before (T(0)), immediately after (T(1)) and
      four hours after (T(2)) exercise. Statistically significant differences in mRNA
      abundance between time points (T(0) vs T(1) and T(0) vs T(2)) were determined
      using the empirical Bayes moderated t-test in the Bioconductor package Linear
      Models for Microarray Data (LIMMA) and the expression of a select panel of genes
      was validated using real time quantitative reverse transcription PCR (qRT-PCR).
      While only two genes had increased expression at T(1) (P < 0.05), by T(2) 932
      genes had increased (P < 0.05) and 562 genes had decreased expression (P < 0.05).
      Functional analysis of genes differentially expressed during the recovery phase
      (T(2)) revealed an over-representation of genes localized to the actin
      cytoskeleton and with functions in the MAPK signalling, focal adhesion, insulin
      signalling, mTOR signaling, p53 signaling and Type II diabetes mellitus pathways.
      At T(1), using a less stringent statistical approach, we observed an over
      representation of genes involved in the stress response, metabolism and
      intracellular signaling. These findings suggest that protein synthesis,
      mechanosensation and muscle remodeling contribute to skeletal muscle adaptation
      towards improved integrity and hypertrophy. CONCLUSIONS: This is the first study
      to characterize global mRNA expression profiles in equine skeletal muscle using
      an equine-specific microarray platform. Here we reveal novel genes and mechanisms
      that are temporally expressed following exercise providing new knowledge about
      the early and late molecular responses to exercise in the equine skeletal muscle
      transcriptome.

PMID- 20042073
TI  - The chemokine CXCL13 is a key regulator of B cell recruitment to the
      cerebrospinal fluid in acute Lyme neuroborreliosis.
AB  - BACKGROUND: The chemokine CXCL13 is known to dictate homing and motility of B
      cells in lymphoid tissue and has been implicated in the formation of ectopic
      lymphoid tissue in chronic inflammation. Whether it influences B cell trafficking
      during acute infection, is largely unclear. In previous studies, we showed that
      (I) CXCL13 levels are markedly increased in the B cell-rich cerebrospinal fluid
      (CSF) of patients with acute Lyme neuroborreliosis (LNB), and (II) CXCL13 is
      released by monocytes upon recognition of borrelial outer surface proteins by
      Toll-like receptor 2. Here, we assessed the role of CXCL13--in comparison to
      other chemokines--in the recruitment of B cells to the CSF of patients with acute
      LNB. METHODS: Measurement of chemokines was done by ELISA. B cells were isolated
      from whole blood using magnetic cell separation (MACS). For migration
      experiments, a modified Boyden chamber assay was used and the migrated B cells
      were further analysed by FACS. The migration was inhibited either by
      preincubation of the CSF samples with neutralizing antibodies, heating to 60
      degrees C, removal of proteins >3 kDa, or by pre-treatment of the B cells with
      pertussis toxin. The principal statistical tests used were one-way analysis of
      variance and Bonferroni test (chemokine measurements) as well as paired Student's
      t-test (migration experiments). RESULTS: Measurements of chemokine levels
      revealed an increase in three of the four known major B cell chemoattractants
      CXCL13, CCL19 and CXCL12 in LNB CSF. The CXCL13 CSF:serum ratio, as a measure of
      the chemotactic gradient, was substantially higher than that of CCL19 and CXCL12.
      Moreover, the chemotactic activity of LNB CSF was reduced up to 56% after
      preincubation with a neutralizing CXCL13 antibody, while combined preincubation
      with antibodies against CXCL13, CCL19, and CXCL12 did not lead to further
      reduction. Since treatment with pertussis toxin, heating to 60 degrees C, and
      removal of proteins >3 kDa abrogated the chemotactic activity, further not yet
      identified chemokines seem to be involved in B cell recruitment to LNB CSF.
      CONCLUSION: Combined, our study suggests a key role of CXCL13 in B cell migration
      to sites of infection as shown here for the CSF of LNB patients.

PMID- 20042074
TI  - Molecular evolution of the hyperthermophilic archaea of the Pyrococcus genus:
      analysis of adaptation to different environmental conditions.
AB  - BACKGROUND: Prokaryotic microorganisms are able to survive and proliferate in
      severe environmental conditions. The increasing number of complete sequences of
      prokaryotic genomes has provided the basis for studying the molecular mechanisms
      of their adaptation at the genomic level. We apply here a computer-based approach
      to compare the genomes and proteomes from P. furiosus, P. horikoshii, and P.
      abyssi to identify features of their molecular evolution related to adaptation
      strategy to diverse environmental conditions. RESULTS: Phylogenetic analysis of
      rRNA genes from 26 Pyrococcus strains suggested that the divergence of P.
      furiosus, P. horikoshii and P. abyssi might have occurred from ancestral deep-sea
      organisms. It was demonstrated that the function of genes that have been subject
      to positive Darwinian selection is closely related to abiotic and biotic
      conditions to which archaea managed to become adapted. Divergence of the P.
      furiosus archaea might have been due to loss of some genes involved in cell
      motility or signal transduction, and/or to evolution under positive selection of
      the genes for translation machinery. In the course of P. horikoshii divergence,
      positive selection was found to operate mainly on the transcription machinery;
      divergence of P. abyssi was related with positive selection for the genes mainly
      involved in inorganic ion transport. Analysis of radical amino acid replacement
      rate in evolving P. furiosus, P. horikoshii and P. abyssi showed that the
      fixation rate was higher for radical substitutions relative to the volume of
      amino acid side-chain. CONCLUSIONS: The current results give due credit to the
      important role of hydrostatic pressure as a cause of variability in the P.
      furiosus, P. horikoshii and P. abyssi genomes evolving in different habitats.
      Nevertheless, adaptation to pressure does not appear to be the sole factor
      ensuring adaptation to environment. For example, at the stage of the divergence
      of P. horikoshii and P. abyssi, an essential evolutionary role may be assigned to
      changes in the trophic chain, namely, acquisition of a consumer status at a high
      (P. horikoshii) or low level (P. abyssi).

PMID- 20042075
TI  - A service-oriented architecture for integrating the modeling and formal
      verification of genetic regulatory networks.
AB  - BACKGROUND: The study of biological networks has led to the development of
      increasingly large and detailed models. Computer tools are essential for the
      simulation of the dynamical behavior of the networks from the model. However, as
      the size of the models grows, it becomes infeasible to manually verify the
      predictions against experimental data or identify interesting features in a large
      number of simulation traces. Formal verification based on temporal logic and
      model checking provides promising methods to automate and scale the analysis of
      the models. However, a framework that tightly integrates modeling and simulation
      tools with model checkers is currently missing, on both the conceptual and the
      implementational level. RESULTS: We have developed a generic and modular web
      service, based on a service-oriented architecture, for integrating the modeling
      and formal verification of genetic regulatory networks. The architecture has been
      implemented in the context of the qualitative modeling and simulation tool GNA
      and the model checkers NUSMV and CADP. GNA has been extended with a verification
      module for the specification and checking of biological properties. The
      verification module also allows the display and visual inspection of the
      verification results. CONCLUSIONS: The practical use of the proposed web service
      is illustrated by means of a scenario involving the analysis of a qualitative
      model of the carbon starvation response in E. coli. The service-oriented
      architecture allows modelers to define the model and proceed with the
      specification and formal verification of the biological properties by means of a
      unified graphical user interface. This guarantees a transparent access to formal
      verification technology for modelers of genetic regulatory networks.

PMID- 20042076
TI  - Predicting functional upstream open reading frames in Saccharomyces cerevisiae.
AB  - BACKGROUND: Some upstream open reading frames (uORFs) regulate gene expression
      (i.e., they are functional) and can play key roles in keeping organisms healthy.
      However, how uORFs are involved in gene regulation is not yet fully understood.
      In order to get a complete view of how uORFs are involved in gene regulation, it
      is expected that a large number of experimentally verified functional uORFs are
      needed. Unfortunately, wet-experiments to verify that uORFs are functional are
      expensive. RESULTS: In this paper, a new computational approach to predicting
      functional uORFs in the yeast Saccharomyces cerevisiae is presented. Our approach
      is based on inductive logic programming and makes use of a novel combination of
      knowledge about biological conservation, Gene Ontology annotations and genes'
      responses to different conditions. Our method results in a set of simple and
      informative hypotheses with an estimated sensitivity of 76%. The hypotheses
      predict 301 further genes to have 398 novel functional uORFs. Three (RPC11, TPK1,
      and FOL1) of these 301 genes have been hypothesised, following wet-experiments,
      by a related study to have functional uORFs. A comparison with another related
      study suggests that eleven of the predicted functional uORFs from genes LDB17,
      HEM3, CIN8, BCK2, PMC1, FAS1, APP1, ACC1, CKA2, SUR1, and ATH1 are strong
      candidates for wet-lab experimental studies. CONCLUSIONS: Learning based
      prediction of functional uORFs can be done with a high sensitivity. The
      predictions made in this study can serve as a list of candidates for subsequent
      wet-lab verification and might help to elucidate the regulatory roles of uORFs.

PMID- 20042077
TI  - Genetic determinants of hair and eye colours in the Scottish and Danish
      populations.
AB  - BACKGROUND: Eye and hair colour is highly variable in the European population,
      and is largely genetically determined. Both linkage and association studies have
      previously been used to identify candidate genes underlying this variation. Many
      of the genes found were previously known as underlying mutant mouse phenotypes or
      human genetic disease, but others, previously unsuspected as pigmentation genes,
      have also been discovered. RESULTS: We assayed the hair of a population of
      individuals of Scottish origin using tristimulus colorimetry, in order to produce
      a quantitative measure of hair colour. Cluster analysis of this data defined two
      groups, with overlapping borders, which corresponded to visually assessed dark
      versus red/light hair colour. The Danish population was assigned into categorical
      hair colour groups. Both cohorts were also assessed for eye colour. DNA from the
      Scottish group was genotyped at SNPs in 33 candidate genes, using 384 SNPs
      identified by HapMap as representatives of each gene. Associations found between
      SNPs and colorimetric hair data and eye colour categories were replicated in a
      cohort of the Danish population. The Danish population was also genotyped with
      SNPs in 4 previously described pigmentation genes. We found replicable
      associations of hair colour with the KITLG and OCA2 genes. MC1R variation
      correlated, as expected, with the red dimension of colorimetric hair colour in
      Scots. The Danish analysis excluded those with red hair, and no associations were
      found with MC1R in this group, emphasising that MC1R regulates the colour rather
      than the intensity of pigmentation. A previously unreported association with the
      HPS3 gene was seen in the Scottish population. However, although this replicated
      in the smaller cohort of the Danish population, no association was seen when the
      whole study population was analysed. CONCLUSIONS: We have found novel
      associations with SNPs in known pigmentation genes and colorimetrically assessed
      hair colour in a Scottish and a Danish population.

PMID- 20042078
TI  - Impact of ubiquitous inhibitors on the GUS gene reporter system: evidence from
      the model plants Arabidopsis, tobacco and rice and correction methods for
      quantitative assays of transgenic and endogenous GUS.
AB  - BACKGROUND: The beta-glucuronidase (GUS) gene reporter system is one of the most
      effective and employed techniques in the study of gene regulation in plant
      molecular biology. Improving protocols for GUS assays have rendered the original
      method described by Jefferson amenable to various requirements and conditions,
      but the serious limitation caused by inhibitors of the enzyme activity in plant
      tissues has thus far been underestimated. RESULTS: We report that inhibitors of
      GUS activity are ubiquitous in organ tissues of Arabidopsis, tobacco and rice,
      and significantly bias quantitative assessment of GUS activity in plant
      transformation experiments. Combined with previous literature reports on non
      model species, our findings suggest that inhibitors may be common components of
      plant cells, with variable affinity towards the E. coli enzyme. The reduced
      inhibitory capacity towards the plant endogenous GUS discredits the hypothesis of
      a regulatory role of these compounds in plant cells, and their effect on the
      bacterial enzyme is better interpreted as a side effect due to their interaction
      with GUS during the assay. This is likely to have a bearing also on histochemical
      analyses, leading to inaccurate evaluations of GUS expression. CONCLUSIONS: In
      order to achieve reliable results, inhibitor activity should be routinely tested
      during quantitative GUS assays. Two separate methods to correct the measured
      activity of the transgenic and endogenous GUS are presented.

PMID- 20042079
TI  - Metabolic investigation of host/pathogen interaction using MS2-infected
      Escherichia coli.
AB  - BACKGROUND: RNA viruses are responsible for a variety of illnesses among people,
      including but not limited to the common cold, the flu, HIV, and ebola. Developing
      new drugs and new strategies for treating diseases caused by these viruses can be
      an expensive and time-consuming process. Mathematical modeling may be used to
      elucidate host-pathogen interactions and highlight potential targets for drug
      development, as well providing the basis for optimizing patient treatment
      strategies. The purpose of this work was to determine whether a genome-scale
      modeling approach could be used to understand how metabolism is impacted by the
      host-pathogen interaction during a viral infection. Escherichia coli/MS2 was used
      as the host-pathogen model system as MS2 is easy to work with, harmless to
      humans, but shares many features with eukaryotic viruses. In addition, the genome
      scale metabolic model of E. coli is the most comprehensive model at this time.
      RESULTS: Employing a metabolic modeling strategy known as "flux balance analysis"
      coupled with experimental studies, we were able to predict how viral infection
      would alter bacterial metabolism. Based on our simulations, we predicted that
      cell growth and biosynthesis of the cell wall would be halted. Furthermore, we
      predicted a substantial increase in metabolic activity of the pentose phosphate
      pathway as a means to enhance viral biosynthesis, while a break down in the
      citric acid cycle was predicted. Also, no changes were predicted in the
      glycolytic pathway. CONCLUSIONS: Through our approach, we have developed a
      technique of modeling virus-infected host metabolism and have investigated the
      metabolic effects of viral infection. These studies may provide insight into how
      to design better drugs. They also illustrate the potential of extending such
      metabolic analysis to higher order organisms, including humans.

PMID- 20042080
TI  - Estimating required information size by quantifying diversity in random-effects
      model meta-analyses.
AB  - BACKGROUND: There is increasing awareness that meta-analyses require a
      sufficiently large information size to detect or reject an anticipated
      intervention effect. The required information size in a meta-analysis may be
      calculated from an anticipated a priori intervention effect or from an
      intervention effect suggested by trials with low-risk of bias. METHODS:
      Information size calculations need to consider the total model variance in a meta
      analysis to control type I and type II errors. Here, we derive an adjusting
      factor for the required information size under any random-effects model meta
      analysis. RESULTS: We devise a measure of diversity (D2) in a meta-analysis,
      which is the relative variance reduction when the meta-analysis model is changed
      from a random-effects into a fixed-effect model. D2 is the percentage that the
      between-trial variability constitutes of the sum of the between-trial variability
      and a sampling error estimate considering the required information size. D2 is
      different from the intuitively obvious adjusting factor based on the common
      quantification of heterogeneity, the inconsistency (I2), which may underestimate
      the required information size. Thus, D2 and I2 are compared and interpreted using
      several simulations and clinical examples. In addition we show mathematically
      that diversity is equal to or greater than inconsistency, that is D2 >or= I2, for
      all meta-analyses. CONCLUSION: We conclude that D2 seems a better alternative
      than I2 to consider model variation in any random-effects meta-analysis despite
      the choice of the between trial variance estimator that constitutes the model.
      Furthermore, D2 can readily adjust the required information size in any random
      effects model meta-analysis.

PMID- 20042081
TI  - The powdery mildew resistance gene REN1 co-segregates with an NBS-LRR gene
      cluster in two Central Asian grapevines.
AB  - BACKGROUND: Grape powdery mildew is caused by the North American native pathogen
      Erysiphe necator. Eurasian Vitis vinifera varieties were all believed to be
      susceptible. REN1 is the first resistance gene naturally found in cultivated
      plants of Vitis vinifera. RESULTS: REN1 is present in 'Kishmish vatkana' and
      'Dzhandzhal kara', two grapevines documented in Central Asia since the 1920's.
      These cultivars have a second-degree relationship (half sibs, grandparent
      grandchild, or avuncular), and share by descent the chromosome on which the
      resistance allele REN1 is located. The REN1 interval was restricted to 1.4 cM
      using 38 SSR markers distributed across the locus and the segregation of the
      resistance phenotype in two progenies of collectively 461 offspring, derived from
      either resistant parent. The boundary markers delimit a 1.4-Mbp sequence in the
      PN40024 reference genome, which contains 27 genes with known functions, 2 full
      length coiled-coil NBS-LRR genes, and 9 NBS-LRR pseudogenes. In the REN1 locus of
      PN40024, NBS genes have proliferated through a mixture of segmental duplications,
      tandem gene duplications, and intragenic recombination between paralogues,
      indicating that the REN1 locus has been inherently prone to producing genetic
      variation. Three SSR markers co-segregate with REN1, the outer ones confining the
      908-kb array of NBS-LRR genes. Kinship and clustering analyses based on genetic
      distances with susceptible cultivars representative of Central Asian Vitis
      vinifera indicated that 'Kishmish vatkana' and 'Dzhandzhal kara' fit well into
      local germplasm. 'Kishmish vatkana' also has a parent-offspring relationship with
      the seedless table grape 'Sultanina'. In addition, the distant genetic
      relatedness to rootstocks, some of which are derived from North American species
      resistant to powdery mildew and have been used worldwide to guard against
      phylloxera since the late 1800's, argues against REN1 being infused into Vitis
      vinifera from a recent interspecific hybridisation. CONCLUSION: The REN1 gene
      resides in an NBS-LRR gene cluster tightly delimited by two flanking SSR markers,
      which can assist in the selection of this DNA block in breeding between Vitis
      vinifera cultivars. The REN1 locus has multiple layers of structural complexity
      compared with its two closely related paralogous NBS clusters, which are located
      some 5 Mbp upstream and 4 Mbp downstream of the REN1 interval on the same
      chromosome.

PMID- 20042082
TI  - Tyrosine phosphorylation of the N-Methyl-D-Aspartate receptor 2B subunit in
      spinal cord contributes to remifentanil-induced postoperative hyperalgesia: the
      preventive effect of ketamine.
AB  - BACKGROUND: Experimental and clinical studies showed that intraoperative infusion
      of remifentanil has been associated with postoperative hyperalgesia. Previous
      reports suggested that spinal N-methyl-D-aspartate (NMDA) receptors may
      contribute to the development and maintenance of opioid-induced hyperalgesia. In
      the present study, we used a rat model of postoperative pain to investigate the
      role of tyrosine phosphorylation of NMDA receptor 2B (NR2B) subunit in spinal
      cord in the postoperative hyperalgesia induced by remifentanil and the
      intervention of pretreatment with ketamine. RESULTS: Intraoperative infusion of
      remifentanil (0.04 mg/kg, subcutaneous) significantly enhanced mechanical
      allodynia and thermal hyperalgesia induced by the plantar incision during the
      postoperative period (each lasting between 2 h and 48 h), which was attenuated by
      pretreatment with ketamine (10 mg/kg, subcutaneous). Correlated with the pain
      behavior changes, immunocytochemical and western blotting experiments in our
      study revealed that there was a marked increase in NR2B phosphorylation at
      Tyr1472 in the superficial dorsal horn after intraoperative infusion of
      remifentanil, which was attenuated by pretreatment with ketamine. CONCLUSIONS:
      This study provides direct evidence that tyrosine phosphorylation of the NR2B at
      Tyr1472 in spinal dosal horn contributes to postoperative hyperalgesia induced by
      remifentanil and supports the potential therapeutic value of ketamine for
      improving postoperative hyperalgesia induced by remifentanil.

PMID- 20042083
TI  - Performance of the auxotrophic Saccharomyces cerevisiae BY4741 as host for the
      production of IL-1beta in aerated fed-batch reactor: role of ACA supplementation,
      strain viability, and maintenance energy.
AB  - BACKGROUND: Saccharomyces cerevisiae BY4741 is an auxotrophic commonly used
      strain. In this work it has been used as host for the expression and secretion of
      human interleukin-1beta (IL1beta), using the cell wall protein Pir4 as fusion
      partner. To achieve high cell density and, consequently, high product yield,
      BY4741 [PIR4-IL1beta] was cultured in an aerated fed-batch reactor, using a
      defined mineral medium supplemented with casamino acids as ACA (auxotrophy
      complementing amino acid) source. Also the S. cerevisiae mutant BY4741 Deltayca1
      [PIR4-IL1beta], carrying the deletion of the YCA1 gene coding for a caspase-like
      protein involved in the apoptotic response, was cultured in aerated fed-batch
      reactor and compared to the parental strain, to test the effect of this mutation
      on strain robustness. Viability of the producer strains was examined during the
      runs and a mathematical model, which took into consideration the viable biomass
      present in the reactor and the glucose consumption for both growth and
      maintenance, was developed to describe and explain the time-course evolution of
      the process for both, the BY4741 parental and the BY4741 Deltayca1 mutant strain.
      RESULTS: Our results show that the concentrations of ACA in the feeding solution,
      corresponding to those routinely used in the literature, are limiting for the
      growth of S. cerevisiae BY4741 [PIR4-IL1beta] in fed-batch reactor. Even in the
      presence of a proper ACA supplementation, S. cerevisiae BY4741 [PIR4-IL1beta] did
      not achieve a high cell density. The Deltayca1 deletion did not have a beneficial
      effect on the overall performance of the strain, but it had a clear effect on its
      viability, which was not impaired during fed-batch operations, as shown by the kd
      value (0.0045 h-1), negligible if compared to that of the parental strain (0.028
      h-1). However, independently of their robustness, both the parental and the
      Deltayca1 mutant ceased to grow early during fed-batch runs, both strains using
      most of the available carbon source for maintenance, rather than for further
      proliferation. The mathematical model used evidenced that the energy demand for
      maintenance was even higher in the case of the Deltayca1 mutant, accounting for
      the growth arrest observed despite the fact that cell viability remained
      comparatively high. CONCLUSIONS: The paper points out the relevance of a proper
      ACA formulation for the outcome of a fed-batch reactor growth carried out with S.
      cerevisiae BY4741 [PIR4-IL1beta] strain and shows the sensitivity of this
      commonly used auxotrophic strain to aerated fed-batch operations. A Deltayca1
      disruption was able to reduce the loss of viability, but not to improve the
      overall performance of the process. A mathematical model has been developed that
      is able to describe the behaviour of both the parental and mutant producer strain
      during fed-batch runs, and evidence the role played by the energy demand for
      maintenance in the outcome of the process.

PMID- 20042084
TI  - Polymorphism in the flanking regions of the PbGP43 gene from the human pathogen
      Paracoccidioides brasiliensis: search for protein binding sequences and poly(A)
      cleavage sites.
AB  - BACKGROUND: Paracoccidioides brasiliensis is a thermo-dimorphic fungus that
      causes paracoccidiodomycosis (PCM). Glycoprotein gp43 is the fungal main
      diagnostic antigen, which can also protect against murine PCM and interact with
      extracellular matrix proteins. It is structurally related to glucanases, however
      not active, and whose expression varies considerably. We have presently studied
      polymorphisms in the PbGP43 flanking regions to help understand such variations.
      RESULTS: we tested the protein-binding capacity of oligonucleotides covering the
      PbGP43 proximal 5' flanking region, including overlap and mutated probes. We used
      electrophoretic mobility shift assays and found DNA binding regions between
      positions -134 to -103 and -255 to -215. Only mutation at -230, characteristic of
      P. brasiliensis phylogenetic species PS2, altered binding affinity. Next, we
      cloned and sequenced the 5' intergenic region up to position -2,047 from P.
      brasiliensis Pb339 and observed that it is composed of three tandem repetitive
      regions of about 500 bp preceded upstream by 442 bp. Correspondent PCR fragments
      of about 2,000 bp were found in eight out of fourteen isolates; in PS2 samples
      they were 1,500-bp long due to the absence of one repetitive region, as detected
      in Pb3. We also compared fifty-six PbGP43 3' UTR sequences from ten isolates and
      have not observed polymorphisms; however we detected two main poly(A) clusters
      (1,420 to 1,441 and 1,451 to 1,457) of multiple cleavage sites. In a single
      isolate we found one to seven sites. CONCLUSIONS: We observed that the amount of
      PbGP43 transcripts accumulated in P. brasiliensis Pb339 grown in defined medium
      was about 1,000-fold higher than in Pb18 and 120-fold higher than in Pb3. We have
      described a series of features in the gene flanking regions and differences among
      isolates, including DNA-binding sequences, which might impact gene regulation.
      Little is known about regulatory sequences in thermo-dimorphic fungi. The
      peculiar structure of tandem repetitive fragments in the 5' intergenic region of
      PbGP43, their characteristic sequences, besides the presence of multiple poly(A)
      cleavage sites in the 3' UTR will certainly guide future studies.

PMID- 20042085
TI  - Endothelin receptor antagonist and airway dysfunction in pulmonary arterial
      hypertension.
AB  - BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH), peripheral
      airway obstruction is frequent. This is partially attributed to the mediator
      dysbalance, particularly an excess of endothelin-1 (ET-1), to increased pulmonary
      vascular and airway tonus and to local inflammation. Bosentan (ET-1 receptor
      antagonist) improves pulmonary hemodynamics, exercise limitation, and disease
      severity in IPAH. We hypothesized that bosentan might affect airway obstruction.
      METHODS: In 32 IPAH-patients (19 female, WHO functional class II (n = 10), III (n
      = 22); (data presented as mean +/- standard deviation) pulmonary vascular
      resistance (11 +/- 5 Wood units), lung function, 6 minute walk test (6-MWT; 364
      +/- 363.7 (range 179.0-627.0) m), systolic pulmonary artery pressure, sPAP, 79 +/
      19 mmHg), and NT-proBNP serum levels (1427 +/- 2162.7 (range 59.3-10342.0) ng/L)
      were measured at baseline, after 3 and 12 months of oral bosentan (125 mg twice
      per day). RESULTS AND DISCUSSION: At baseline, maximal expiratory flow at 50 and
      25% vital capacity were reduced to 65 +/- 25 and 45 +/- 24% predicted. Total lung
      capacity was 95.6 +/- 12.5% predicted and residual volume was 109 +/- 21.4%
      predicted. During 3 and 12 months of treatment, 6-MWT increased by 32 +/- 19 and
      53 +/- 69 m, respectively; p < 0.01; whereas sPAP decreased by 7 +/- 14 and 10 +/
      19 mmHg, respectively; p < 0.05. NT-proBNP serum levels tended to be reduced by
      123 +/- 327 and by 529 +/- 1942 ng/L; p = 0.11). There was no difference in
      expiratory flows or lung volumes during 3 and 12 months. CONCLUSION: This study
      gives first evidence in IPAH, that during long-term bosentan, improvement of
      hemodynamics, functional parameters or serum biomarker occur independently from
      persisting peripheral airway obstruction.

PMID- 20042086
TI  - Quantitative analysis of replication-related mutation and selection pressures in
      bacterial chromosomes and plasmids using generalised GC skew index.
AB  - BACKGROUND: Due to their bi-directional replication machinery starting from a
      single finite origin, bacterial genomes show characteristic nucleotide
      compositional bias between the two replichores, which can be visualised through
      GC skew or (C-G)/(C+G). Although this polarisation is used for computational
      prediction of replication origins in many bacterial genomes, the degree of GC
      skew visibility varies widely among different species, necessitating a
      quantitative measurement of GC skew strength in order to provide confidence
      measures for GC skew-based predictions of replication origins. RESULTS: Here we
      discuss a quantitative index for the measurement of GC skew strength, named the
      generalised GC skew index (gGCSI), which is applicable to genomes of any length,
      including bacterial chromosomes and plasmids. We demonstrate that gGCSI is
      independent of the window size and can thus be used to compare genomes with
      different sizes, such as bacterial chromosomes and plasmids. It can suggest the
      existence of different replication mechanisms in archaea and of rolling-circle
      replication in plasmids. Correlation of gGCSI values between plasmids and their
      corresponding host chromosomes suggests that within the same strain, these
      replicons have reproduced using the same replication machinery and thus exhibit
      similar strengths of replication strand skew. CONCLUSIONS: gGCSI can be applied
      to genomes of any length and thus allows comparative study of replication-related
      mutation and selection pressures in genomes of different lengths such as
      bacterial chromosomes and plasmids. Using gGCSI, we showed that replication
      related mutation or selection pressure is similar for replicons with similar
      machinery.

PMID- 20042088
TI  - Immunological mechanisms underlying protection mediated by RTS,S: a review of the
      available data.
AB  - The RTS,S/AS candidate malaria vaccine has demonstrated efficacy against a
      variety of endpoints in Phase IIa and Phase IIb trials over more than a decade. A
      multi-country phase III trial of RTS,S/AS01 is now underway with submission as
      early as 2012, if vaccine safety and efficacy are confirmed. The immunologic
      basis for how the vaccine protects against both infection and disease remains
      uncertain. It is, therefore, timely to review the information currently available
      about the vaccine with regard to how it impacts the human-Plasmodium falciparum
      host-pathogen relationship. In this article, what is known about mechanisms
      involved in partial protection against malaria induced by RTS,S is reviewed.

PMID- 20042087
TI  - Deep RNA sequencing of L. monocytogenes reveals overlapping and extensive
      stationary phase and sigma B-dependent transcriptomes, including multiple highly
      transcribed noncoding RNAs.
AB  - BACKGROUND: Identification of specific genes and gene expression patterns
      important for bacterial survival, transmission and pathogenesis is critically
      needed to enable development of more effective pathogen control strategies. The
      stationary phase stress response transcriptome, including many sigmaB-dependent
      genes, was defined for the human bacterial pathogen Listeria monocytogenes using
      RNA sequencing (RNA-Seq) with the Illumina Genome Analyzer. Specifically,
      bacterial transcriptomes were compared between stationary phase cells of L.
      monocytogenes 10403S and an otherwise isogenic DeltasigB mutant, which does not
      express the alternative sigma factor sigmaB, a major regulator of genes
      contributing to stress response, including stresses encountered upon entry into
      stationary phase. RESULTS: Overall, 83% of all L. monocytogenes genes were
      transcribed in stationary phase cells; 42% of currently annotated L.
      monocytogenes genes showed medium to high transcript levels under these
      conditions. A total of 96 genes had significantly higher transcript levels in
      10403S than in DeltasigB, indicating sigmaB-dependent transcription of these
      genes. RNA-Seq analyses indicate that a total of 67 noncoding RNA molecules
      (ncRNAs) are transcribed in stationary phase L. monocytogenes, including 7
      previously unrecognized putative ncRNAs. Application of a dynamically trained
      Hidden Markov Model, in combination with RNA-Seq data, identified 65 putative
      sigmaB promoters upstream of 82 of the 96 sigmaB-dependent genes and upstream of
      the one sigmaB-dependent ncRNA. The RNA-Seq data also enabled annotation of
      putative operons as well as visualization of 5'- and 3'-UTR regions. CONCLUSIONS:
      The results from these studies provide powerful evidence that RNA-Seq data
      combined with appropriate bioinformatics tools allow quantitative
      characterization of prokaryotic transcriptomes, thus providing exciting new
      strategies for exploring transcriptional regulatory networks in bacteria.

PMID- 20042089
TI  - Methylation associated inactivation of RASSF1A and its synergistic effect with
      activated K-Ras in nasopharyngeal carcinoma.
AB  - BACKGROUND: Epigenetic silencing of tumor suppressor genes associated with
      promoter methylation is considered to be a hallmark of oncogenesis. RASSF1A is a
      candidate tumor suppressor gene which was found to be inactivated in many human
      cancers. Although we have had a preliminary cognition about the function of
      RASSF1A, the exact mechanisms about how RASSF1A functions in human cancers were
      largely unknown. Moreover, the effect of mutated K-Ras gene on the function of
      RASSF1A is lacking. The aim of this study was to investigate the expression
      profile and methylation status of RASSF1A gene, and to explore its concrete
      mechanisms as a tumor suppressor gene in Nasopharyngeal Carcinoma. METHODS: We
      examined the expression profile and methylation status of RASSF1A in two NPC cell
      lines, 38 primary nasopharyngeal carcinoma and 14 normal nasopharyngeal epithelia
      using RT-PCR and methylated specific PCR(MSP) respectively. 5-aza-dC was then
      added to confirm the correlation between hypermethylation status and inactivation
      of RASSF1A. The NPC cell line CNE-2 was transfected with exogenous
      pcDNA3.1(+)/RASSF1A plasmid in the presence or absence of mutated K-Ras by
      liposome-mediated gene transfer method. Flow cytometry was used to examine the
      effect of RASSF1A on cell cycle modulation and apoptosis. Meanwhile, trypan blue
      dye exclusion assays was used to detect the effect of RASSF1A transfection alone
      and the co-transfection of RASSF1A and K-Ras on cell proliferation. RESULTS:
      Promoter methylation of RASSF1A could be detected in 71.05% (27/38) of NPC
      samples, but not in normal nasopharyngeal epithelia. RASSF1A expression in NPC
      primary tumors was lower than that in normal nasopharyngeal epithelial (p <
      0.01). Expression of RASSF1A was down-regulated in two NPC cell lines. Loss of
      RASSF1A expression was greatly restored by the methyltransferase inhibitor 5-aza
      dC in CNE-2. Ectopic expression of RASSF1A in CNE-2 could increase the percentage
      of G0/G1 phase cells (p < 0.01), inhibit cell proliferation and induce apoptosis
      (p < 0.001). Moreover, activated K-Ras could enhance the growth inhibition effect
      induced by RASSF1A in CNE-2 cells (p < 0.01). CONCLUSION: Expression of RASSF1A
      is down-regulated in NPC due to the hypermethylation of promoter. Exogenous
      expression of RASSF1A is able to induce growth inhibition effect and apoptosis in
      tumor cell lines, and this effect could be enhanced by activated K-Ras.

PMID- 20042090
TI  - Policies to improve end-of-life decisions in Flemish hospitals: communication,
      training of health care providers and use of quality assessments.
AB  - BACKGROUND: The prevalence and implementation of institutional end-of-life
      policies has been comprehensively studied in Flanders, Belgium, a country where
      euthanasia was legalised in 2002. Developing end-of-life policies in hospitals is
      a first step towards improving the quality of medical decision-making at the end
      of-life. Implementation of policies through quality assessments, communication
      and the training and education of health care providers is equally important in
      improving actual end-of-life practice. The aim of the present study is to report
      on the existence and nature of end-of-life policy implementation activities in
      Flemish acute hospitals. METHODS: A cross-sectional mail survey was sent to all
      acute hospitals (67 main campuses) in Flanders (Belgium). The questionnaire asked
      about hospital characteristics, the prevalence of policies on five types of end
      of-life decisions: euthanasia, palliative sedation, alleviation of symptoms with
      possible life-shortening effect, do-not-resuscitate decision, and withdrawing or
      withholding of treatment, the internal and external communication of these
      policies, training and education on aspects of end-of-life care, and quality
      assessments of end-of-life care on patient and family level. RESULTS: The
      response rate was 55%. Results show that in 2007 written policies on most types
      of end-of-life decisions were widespread in acute hospitals (euthanasia: 97%, do
      not-resuscitate decisions: 98%, palliative sedation: 79%). While standard
      communication of these policies to health care providers was between 71% and 91%,
      it was much lower to patients and/or family (between 17% and 50%). More than 60%
      of institutions trained and educated their caregivers in different aspects on end
      of-life care. Assessment of the quality of these different aspects at patient and
      family level occurred in 25% to 61% of these hospitals. CONCLUSIONS: Most Flemish
      acute hospitals have developed a policy on end-of-life practices. However,
      communication, training and the education of health care providers about these
      policies is not always provided, and quality assessment tools are used in less
      than half of the hospitals.

PMID- 20042091
TI  - Cancer patients' attitudes towards Chinese medicine: a Hong Kong survey.
AB  - BACKGROUND: This article reports a survey conducted in Hong Kong on the cancer
      patients' attitudes towards Chinese medicine treatment. METHODS: Cancer patients
      from three Chinese medicine clinics and one oncology clinic were interviewed with
      a structured questionnaire. RESULTS: Of a total of 786 participants included in
      the study, 42.9% used Western medicine only; 57.1% used at least one form of
      Chinese medicine; 5 participants used Chinese medicine only; and 56.5% used
      Chinese medicine before/during/after Western medicine treatment. Commonly used
      Western medicine and Chinese medicine treatments included chemotherapy (63.7%),
      radiotherapy (62.0%), surgery (57.6%), Chinese herbal medicine (53.9%) and
      Chinese dietary therapy (9.5%). Participants receiving chemotherapy used Chinese
      medicine (63.3%) more than those receiving any other Western medicine treatments.
      Spearman correlation coefficients showed that the selection of Chinese medicine
      was associated with the cancer type (r(s)= -1.36; P < 0.001), stage (r(s)= 0.178;
      P < 0.001), duration (r(s)= -0.074; P = 0.037), whether receiving chemotherapy
      (r(s)= 0.165; P < 0.001) and palliative therapy (r(s)= 0.087; P = 0.015). Nearly
      two-thirds of the participants (N = 274) did not tell their physicians about
      using Chinese medicine. Over two-thirds of all participants (68.2%) believed that
      integrated Chinese and Western medicine was effective. CONCLUSION: Chinese
      medicine is commonly used among Hong Kong cancer patients. The interviewed cancer
      patients in Hong Kong considered integrative Chinese and Western medicine is an
      effective cancer treatment.

PMID- 20042092
TI  - Design and methods for testing a simple dietary message to improve weight loss
      and dietary quality.
AB  - BACKGROUND: The current food pyramid guidelines have been criticized because of
      their complexity and the knowledge required for users to understand the
      recommendations. Simplification of a dietary message to focus on a single key
      aspect of dietary quality, e.g., fiber intake, may make the message much easier
      to comprehend and adhere, such that respondents can achieve greater weight loss,
      better dietary quality and overall metabolic health. METHODS AND DESIGN: This is
      a randomized controlled clinical trial with two equal sized arms. In total, 240
      obese adults who meet diagnostic criteria for the metabolic syndrome will be
      randomized to one of the two conditions: 1) a high fiber diet and 2) the American
      Heart Association (AHA) diet. In the high fiber diet condition, patients will be
      given instruction only on achieving daily dietary fiber intake of 30 g or more.
      In the AHA diet condition, patients will be instructed to make the several
      dietary changes recommended by the AHA 2006 guidelines. The trial examines
      participant weight loss and dietary quality as well as changes in components of
      the metabolic syndrome, inflammatory biomarkers, low-density lipoprotein
      cholesterol levels, insulin levels, and glycosolated hemoglobin. Potential
      mediators, i.e., diet adherence and perceived ease of the diet, and the
      intervention effect on weight change will also be examined. DISCUSSIONS: The
      purpose of this paper is to outline the study design and methods for testing the
      simple message of increasing dietary fiber. If the simple dietary approach is
      found efficacious for weight loss; and, improves dietary quality, metabolic
      health, and adherence, it might then be used to develop a simple public health
      message. TRIAL REGISTRATION: NCT00911885.

PMID- 20042093
TI  - Skittle: a 2-dimensional genome visualization tool.
AB  - BACKGROUND: It is increasingly evident that there are multiple and overlapping
      patterns within the genome, and that these patterns contain different types of
      information--regarding both genome function and genome history. In order to
      discover additional genomic patterns which may have biological significance,
      novel strategies are required. To partially address this need, we introduce a new
      data visualization tool entitled Skittle. RESULTS: This program first creates a 2
      dimensional nucleotide display by assigning four colors to the four nucleotides,
      and then text-wraps to a user adjustable width. This nucleotide display is
      accompanied by a "repeat map" which comprehensively displays all local repeating
      units, based upon analysis of all possible local alignments. Skittle includes a
      smooth-zooming interface which allows the user to analyze genomic patterns at any
      scale.Skittle is especially useful in identifying and analyzing tandem repeats,
      including repeats not normally detectable by other methods. However, Skittle is
      also more generally useful for analysis of any genomic data, allowing users to
      correlate published annotations and observable visual patterns, and allowing for
      sequence and construct quality control. CONCLUSIONS: Preliminary observations
      using Skittle reveal intriguing genomic patterns not otherwise obvious, including
      structured variations inside tandem repeats. The striking visual patterns
      revealed by Skittle appear to be useful for hypothesis development, and have
      already led the authors to theorize that imperfect tandem repeats could act as
      information carriers, and may form tertiary structures within the interphase
      nucleus.

PMID- 20042094
TI  - Genome-wide dissection of globally emergent multi-drug resistant serotype 19A
      Streptococcus pneumoniae.
AB  - BACKGROUND: Emergence of multi-drug resistant (MDR) serotype 19A Streptococcus
      pneumoniae (SPN) is well-documented but causal factors remain unclear. Canadian
      SPN isolates (1993-2008, n = 11,083) were serotyped and in vitro susceptibility
      tested. A subset of MDR 19A were multi-locus sequence typed (MLST) and
      representative isolates' whole genomes sequenced. RESULTS: MDR 19A increased in
      the post-PCV7 era while 19F, 6B, and 23F concurrently declined. MLST of MDR 19A
      (n = 97) revealed that sequence type (ST) 320 predominated. ST320 was unique
      amongst MDR 19A in that its minimum inhibitory concentration (MIC) values for
      penicillin, amoxicillin, ceftriaxone, and erythromycin were higher than for other
      ST present amongst post-PCV7 MDR 19A. DNA sequencing revealed that alleles at key
      drug resistance loci pbp2a, pbp2x, pbp2b, ermB, mefA/E, and tetM were conserved
      between pre-PCV7 ST 320 19F and post-PCV7 ST 320 19A most likely due to a capsule
      switch recombination event. A genome wide comparison of MDR 19A ST320 with MDR
      19F ST320 identified 822 unique SNPs in 19A, 61 of which were present in
      antimicrobial resistance genes and 100 in virulence factors. CONCLUSIONS: Our
      results suggest a complex genetic picture where high-level drug resistance,
      vaccine selection pressure, and SPN mutational events have created a "perfect
      storm" for the emergence of MDR 19A.

PMID- 20042095
TI  - The Nordic Subpopulation Research Programme: prediction of treatment outcome in
      patients with low back pain treated by chiropractors--does the psychological
      profile matter?
AB  - BACKGROUND: It is clinically important to be able to select patients suitable for
      treatment and to be able to predict with some certainty the outcome for patients
      treated for low back pain (LBP). It is not known to what degree outcome among
      chiropractic patients is affected by psychological factors. OBJECTIVES: To
      investigate if some demographic, psychological, and clinical variables can
      predict outcome with chiropractic care in patients with LBP. METHODS: A
      prospective multi-center practice-based study was carried out, in which
      demographic, clinical and psychological information was collected at base-line.
      Outcome was established at the 4(th )visit and after three months. The predictive
      value was studied for all base-line variables, individually and in a
      multivariable analysis. RESULTS: In all, 55 of 99 invited chiropractors collected
      information on 731 patients. At the 4(th )visit data were available on 626
      patients and on 464 patients after 3 months. Fee subsidization (OR 3.2; 95% CI
      1.9-5.5), total duration of pain in the past year (OR 1.5; 95% CI 1.0-2.2), and
      general health (OR 1.2; 95% CI 1.1-1.4) remained in the final model as predictors
      of treatment outcome at the 4(th )visit. The sensitivity was low (12%), whereas
      the specificity was high (97%). At the three months follow-up, duration of pain
      in the past year (OR 2.1; 95% CI 1.4-3.1), and pain in other parts of the spine
      in the past year (OR1.6; 1.1-2.5) were independently associated with outcome.
      However, both the sensitivity and specificity were relatively low (60% and 50%).
      The addition of the psychological variables did not improve the models and none
      of the psychological variables remained significant in the final analyses. There
      was a positive gradient in relation to the number of positive predictor variables
      and outcome, both at the 4(th )visit and after 3 months. CONCLUSION:
      Psychological factors were not found to be relevant in the prediction of
      treatment outcome in Swedish chiropractic patients with LBP.

PMID- 20042096
TI  - Traits associated with innate and adaptive immunity in pigs: heritability and
      associations with performance under different health status conditions.
AB  - There is a need for genetic markers or biomarkers that can predict resistance
      towards a wide range of infectious diseases, especially within a health
      environment typical of commercial farms. Such markers also need to be heritable
      under these conditions and ideally correlate with commercial performance traits.
      In this study, we estimated the heritabilities of a wide range of immune traits,
      as potential biomarkers, and measured their relationship with performance within
      both specific pathogen-free (SPF) and non-SPF environments. Immune traits were
      measured in 674 SPF pigs and 606 non-SPF pigs, which were subsets of the
      populations for which we had performance measurements (average daily gain), viz.
      1549 SPF pigs and 1093 non-SPF pigs. Immune traits measured included total and
      differential white blood cell counts, peripheral blood mononuclear leucocyte
      (PBML) subsets (CD4+ cells, total CD8alpha+ cells, classical CD8alphabeta+ cells,
      CD11R1+ cells (CD8alpha+ and CD8alpha-), B cells, monocytes and CD16+ cells) and
      acute phase proteins (alpha-1 acid glycoprotein (AGP), haptoglobin, C-reactive
      protein (CRP) and transthyretin). Nearly all traits tested were heritable
      regardless of health status, although the heritability estimate for average daily
      gain was lower under non-SPF conditions. There were also negative genetic
      correlations between performance and the following immune traits: CD11R1+ cells,
      monocytes and the acute phase protein AGP. The strength of the association
      between performance and AGP was not affected by health status. However, negative
      genetic correlations were only apparent between performance and monocytes under
      SPF conditions and between performance and CD11R1+ cells under non-SPF
      conditions. Although we cannot infer causality in these relationships, these
      results suggest a role for using some immune traits, particularly CD11R1+ cells
      or AGP concentrations, as predictors of pig performance under the lower health
      status conditions associated with commercial farms.

PMID- 20042097
TI  - Are the processes recommended by the NHMRC for improving Cardiac Rehabilitation
      (CR) for Aboriginal and Torres Strait Islander people being implemented?: an
      assessment of CR Services across Western Australia.
AB  - BACKGROUND: Cardiovascular disease is the major cause of premature death of
      Indigenous Australians, and despite evidence that cardiac rehabilitation (CR) and
      secondary prevention can reduce recurrent disease and deaths, CR uptake is
      suboptimal. The National Health and Medical Research Council (NHMRC) guidelines
      Strengthening Cardiac Rehabilitation and Secondary Prevention for Aboriginal and
      Torres Strait Islander peoples, published in 2005, provide checklists for
      services to assist them to reduce the service gap for Indigenous people. This
      study describes health professionals' awareness, implementation, and perspectives
      of barriers to implementation of these guidelines based on semi-structured
      interviews conducted between November 2007 and June 2008 with health
      professionals involved in CR within mainstream health services in Western
      Australia (WA). Twenty-four health professionals from 17 services (10 rural, 7
      metropolitan) listed in the WA Directory of CR services were interviewed.
      RESULTS: The majority of respondents reported that they were unfamiliar with the
      NHMRC guidelines and as a consequence implementation of the recommendations was
      minimal and inconsistently applied. Respondents reported that they provided few
      in-patient CR-related services to Indigenous patients, services upon discharge
      were erratic, and they had few Indigenous-specific resources for patients. Issues
      relating to workforce, cultural competence, and service linkages emerged as
      having most impact on design and delivery of CR services for Indigenous people in
      WA. CONCLUSIONS: This study has demonstrated limited awareness and poor
      implementation in WA of the recommendations of the NHMRC Strengthening Cardiac
      Rehabilitation and Secondary Prevention for Aboriginal and Torres Strait Islander
      Peoples: A Guide for Health Professionals. The disproportionate burden of CVD
      morbidity and mortality among Indigenous Australians mandates urgent attention to
      this problem and alternative approaches to CR delivery. Dedicated resources and
      alternative approaches to CR delivery for Indigenous Australians are needed.

PMID- 20042098
TI  - Potential contribution of prescription practices to the emergence and spread of
      chloroquine resistance in south-west Nigeria: caution in the use of artemisinin
      combination therapy.
AB  - BACKGROUND: Prescription practices have been shown to influence the emergence of
      anti-malarial drug resistance. Thus efforts in this study were devoted to
      evaluating the prescribing practices prior to introduction of the artemisinin
      based combination therapy (ACT) in Nigeria and its potential contribution to
      emergence of chloroquine resistant malaria in south-west Nigeria, in order to
      forestall a similar situation with the ACT. METHODS: A retrospective quantitative
      study was designed to examine case records of patients treated for malaria in
      either a government or a private hospital in Ibadan, south-west Nigeria, over a
      20-year period, cutting across three phases of resistance to chloroquine in
      Nigeria: pre-resistance, emerging resistance and dissemination of resistance.
      Patient prescriptions were examined for use of anti-malarial drugs, sub
      therapeutic doses of chloroquine, co-administration of anti-histamines with
      chloroquine. Descriptive statistics of frequency and percentage were used to
      describe trends in the parameters assessed using EPI-info. RESULTS: Case record
      files of 2,529 patients were examined. Chloroquine was the main drug used in
      treatment of malaria throughout the periods studied, with frequency of
      prescription at both sites ranging from 91.4% to 98.3% during the pre-resistance
      years. It was administered as standard doses during the pre resistance years.
      Anti-histamines, especially promethazine, were routinely co-administered with
      chloroquine at this period too. However, the practice of prescribing sub
      therapeutic doses of chloroquine at the private health care facility coincided
      with the latter phase of emerging resistance and phase of dissemination of
      resistance. Frequency of prescription of sub-therapeutic doses increased from
      6.7% in 1983 (pre-resistance years) to 43.6% in 1997 (dissemination of resistance
      phase) at the private health care facility. Frequency of co-administration of
      anti-histamines with chloroquine also reduced during the period of dissemination
      of resistance. CONCLUSION: The results from this study describe a lack of
      adherence to national treatment guidelines, especially in the private sector, and
      a relationship between prescription practices and dissemination of drug resistant
      falciparum malaria. As Nigeria adopts the use of ACT, there is an urgent need to
      improve malaria treatment practices in Nigeria in order to prolong the clinical
      shelf-life of the combination.

PMID- 20042099
TI  - Effects of phone versus mail survey methods on the measurement of health-related
      quality of life and emotional and behavioural problems in adolescents.
AB  - BACKGROUND: Telephone interviews have become established as an alternative to
      traditional mail surveys for collecting epidemiological data in public health
      research. However, the use of telephone and mail surveys raises the question of
      to what extent the results of different data collection methods deviate from one
      another. We therefore set out to study possible differences in using telephone
      and mail survey methods to measure health-related quality of life and emotional
      and behavioural problems in children and adolescents. METHODS: A total of 1700
      German children aged 8-18 years and their parents were interviewed randomly
      either by telephone or by mail. Health-related Quality of Life (HRQoL) and mental
      health problems (MHP) were assessed using the KINDL-R Quality of Life instrument
      and the Strengths and Difficulties Questionnaire (SDQ) children's self-report and
      parent proxy report versions. Mean Differences ("d" effect size) and differences
      in Cronbach alpha were examined across modes of administration. Pearson
      correlation between children's and parents' scores was calculated within a multi
      trait-multi-method (MTMM) analysis and compared across survey modes using Fisher
      Z transformation. RESULTS: Telephone and mail survey methods resulted in similar
      completion rates and similar socio-demographic and socio-economic makeups of the
      samples. Telephone methods resulted in more positive self- and parent proxy
      reports of children's HRQoL (SMD < or = 0.27) and MHP (SMD < or = 0.32) on many
      scales. For the phone administered KINDL, lower Cronbach alpha values (self/proxy
      Total: 0.79/0.84) were observed (mail survey self/proxy Total: 0.84/0.87). KINDL
      MTMM results were weaker for the phone surveys: mono-trait-multi-method mean r =
      0.31 (mail: r = 0.45); multi-trait-mono-method mean (self/parents) r = 0.29/0.36
      (mail: r = 0.34/0.40); multi-trait-multi-method mean r = 0.14 (mail: r = 0.21).
      Weaker MTMM results were also observed for the phone administered SDQ: mono-trait
      multi-method mean r = 0.32 (mail: r = 0.40); multi-trait-mono-method mean
      (self/parents) r = 0.24/0.30 (mail: r = 0.20/0.32); multi-trait-multi-method mean
      r = 0.14 (mail = 0.14). The SDQ classification into borderline and abnormal for
      some scales was affected by the method (OR = 0.36-1.55). CONCLUSIONS: The
      observed differences between phone and mail surveys are small but should be
      regarded as relevant in certain settings. Therefore, while both methods are
      valid, some changes are necessary. The weaker reliability and MTMM validity
      associated with phone methods necessitates improved phone adaptations of paper
      and pencil questionnaires. The effects of phone versus mail survey modes are
      partly different across constructs/measures.

PMID- 20042101
TI  - An asymmetric approach to preserve common intervals while sorting by reversals.
AB  - BACKGROUND: The reversal distance and optimal sequences of reversals to transform
      a genome into another are useful tools to analyse evolutionary scenarios.
      However, the number of sequences is huge and some additional criteria should be
      used to obtain a more accurate analysis. One strategy is searching for sequences
      that respect constraints, such as the common intervals (clusters of co-localised
      genes). Another approach is to explore the whole space of sorting sequences,
      eventually grouping them into classes of equivalence. Recently both strategies
      started to be put together, to restrain the space to the sequences that respect
      constraints. In particular an algorithm has been proposed to list classes whose
      sorting sequences do not break the common intervals detected between the two
      initial genomes A and B. This approach may reduce the space of sequences and is
      symmetric (the result of the analysis sorting A into B can be obtained from the
      analysis sorting B into A). RESULTS: We propose an alternative approach to
      restrain the space of sorting sequences, using progressive instead of initial
      detection of common intervals (the list of common intervals is updated after
      applying each reversal). This may reduce the space of sequences even more, but is
      shown to be asymmetric. CONCLUSIONS: We suggest that our method may be more
      realistic when the relation ancestor-descendant between the analysed genomes is
      clear and we apply it to do a better characterisation of the evolutionary
      scenario of the bacterium Rickettsia felis with respect to one of its ancestors.

PMID- 20042100
TI  - Design and pre-clinical profiling of a Plasmodium falciparum MSP-3 derived
      component for a multi-valent virosomal malaria vaccine.
AB  - BACKGROUND: Clinical profiling of two components for a synthetic peptide-based
      virosomal malaria vaccine has yielded promising results, encouraging the search
      for additional components for inclusion in a final multi-valent vaccine
      formulation. This report describes the immunological characterization of linear
      and cyclized synthetic peptides comprising amino acids 211-237 of Plasmodium
      falciparum merozoite surface protein (MSP-3). METHODS: These peptides were
      coupled to phosphatidylethanolamine (PE); the conjugates were intercalated into
      immunopotentiating reconstituted influenza virosomes (IRIVs) and then used for
      immunizations in mice to evaluate their capacity to elicit P. falciparum cross
      reactive antibodies. RESULTS: While all MSP-3-derived peptides were able to
      elicit parasite-binding antibodies, stabilization of turn structures by
      cyclization had no immune-enhancing effect. Therefore, further pre-clinical
      profiling was focused on FB-12, a PE conjugate of the linear peptide. Consistent
      with the immunological results obtained in mice, all FB-12 immunized rabbits
      tested seroconverted and consistently elicited antibodies that interacted with
      blood stage parasites. It was observed that a dose of 50 microg was superior to a
      dose of 10 microg and that influenza pre-existing immunity improved the
      immunogenicity of FB-12 in rabbits. FB-12 production was successfully up-scaled
      and the immunogenicity of a vaccine formulation, produced according to the rules
      of Good Manufacturing Practice (GMP), was tested in mice and rabbits. All animals
      tested developed parasite-binding antibodies. Comparison of ELISA and IFA titers
      as well as the characterization of a panel of anti-FB-12 monoclonal antibodies
      indicated that at least the majority of antibodies specific for the virosomally
      formulated synthetic peptide were parasite cross-reactive. CONCLUSION: These
      results reconfirm the suitability of IRIVs as a carrier/adjuvant system for the
      induction of strong humoral immune responses against a wide range of synthetic
      peptide antigens. The virosomal formulation of the FB-12 peptidomimetic is
      suitable for use in humans and represents a candidate component for a virosomal
      multi-valent malaria subunit vaccine.

PMID- 20042102
TI  - Luteinizing hormone and androstendione are independent predictors of ovulation
      after laparoscopic ovarian drilling: a retrospective cohort study.
AB  - BACKGROUND: Our objective was to investigate luteinizing hormone, follicle
      stimulating hormone, testosterone, and androstenedione as predicitve markers for
      ovulation after laparoscopic ovarian drilling. METHODS: We retrospectively
      analyzed 100 clompihen-resistant patients with the polycystic ovary syndrome who
      underwent laparoscopic ovarian drilling at our department. The main outcome
      measure was spontaneous postoperative ovulation within three months after
      laparoscopic ovarian drilling. In order to predict spontaneous ovulation, we
      tested the following parameters by use of a univariate followed by a multivariate
      regression model: Preoperative serum levels of LH, FSH, testosterone, and
      androstenedione as well as patients' age and body mass index. In addition, we
      focused on pregnancy and life birth rates. RESULTS: Spontaneous ovulation was
      documented in 71/100 patients (71.0%). In a univariate and multivariate analysis,
      luteinizing hormone (OR 1.58, 95%CI: 1.30-1.92) and androstenedione (OR 3.03,
      95%CI: 1.20-7.67), but not follicle-stimulating hormone and testosterone were
      independent predictors of ovulation. Using a cut-off for luteinizing hormone and
      androstenedione of 12.1 IU/l and 3.26 ng/ml, respectively, spontaneous ovulation
      was observed in 63/70 (90.0%) and 36/42 patients (85.7%) with elevated and in
      8/30 (26.7%) and 35/58 (60.3%) patients with low luteinizing hormone and
      androstenedione levels, respectively. The sensitivity, specificity, positive and
      negative predictive values for luteinizing hormone and androstendione as
      predictors of spontaneous ovulation after ovarian drilling were 88.7% (95%CI:
      79.0-95.0%), 75.9% (95%CI: 56.5-89.7%), 90.0% (95%CI: 80.5-95.8%), and 73.3%
      (95%CI: 54.1-87.7%) for luteinizing hormone, and 50.7% (95%CI: 38.6-62.8%), 79.3%
      (95%CI: 60.3-92.0%), 85.7% (95%CI: 71.5-94.6%), and 39.7% (95%CI: 27.0-53.4%) for
      androstenedione, respectively. Complete one-year follow-up was available for
      74/100 patients (74%). We observed a one-year pregnancy rate and a resulting life
      birth rate of 61% and 51%, respectively. CONCLUSIONS: Luteinizing hormone and
      androstenedione prior to laparoscopic ovarian drilling are independent predictors
      of spontaneous ovulation within three months of surgery. We suggest to
      preferentially performing laparoscopic ovarian drilling in patients with high
      luteinizing hormone and androstenedione levels.

PMID- 20042103
TI  - Transgenic fat-1 mouse as a model to study the pathophysiology of cardiovascular,
      neurological and psychiatric disorders.
AB  - Polyunsaturated fatty acids (PUFAs) form an important constituent of all the cell
      membranes in the body. PUFAs such as arachidonic acid (AA), eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA) form precursors to both pro-inflammatory and
      anti-inflammatory compounds. Low-grade systemic inflammation occurs in clinical
      conditions such as insulin resistance, hypertension, type 2 diabetes mellitus,
      atherosclerosis, coronary heart disease, lupus, schizophrenia, Alzheimer's
      disease, and other dementias, cancer and non-alcoholic fatty liver disease
      (NAFLD) that are also characterized by an alteration in the metabolism of
      essential fatty acids in the form of excess production of pro-inflammatory
      eicosanoids and possibly, decreased synthesis and release of anti-inflammatory
      lipoxins, resolvins, protectins and maresins. We propose that low-grade systemic
      inflammation observed in these clinical conditions is due to an imbalance in the
      metabolism of essential fatty acids that is more in favour of pro-inflammatory
      molecules. In this context, transgenic fat-1 mouse that is designed to convert n
      6 to n-3 fatty acids could form an ideal model to study the altered metabolism of
      essential fatty acids in the above mentioned conditions. It is envisaged that low
      grade systemic inflammatory conditions are much less likely in the fat-1 mouse
      and/or these diseases will run a relatively mild course. Identifying the anti
      inflammatory compounds from n-3 fatty acids that suppress low-grade systemic
      inflammatory conditions and understanding their mechanism(s) of action may lead
      to newer therapeutic strategies.

PMID- 20042104
TI  - Correlating measurements across samples improves accuracy of large-scale
      expression profile experiments.
AB  - Gene expression profiling technologies suffer from poor reproducibility across
      replicate experiments. However, when analyzing large datasets, probe-level
      expression profile correlation can help identify flawed probes and lead to the
      construction of truer probe sets with improved reproducibility. We describe
      methods to eliminate uninformative and flawed probes, account for dependence
      between probes, and address variability due to transcript-isoform mixtures. We
      test and validate our approach on Affymetrix microarrays and outline their future
      adaptation to other technologies.

PMID- 20042105
TI  - Incarceration experiences among a community-recruited sample of injection drug
      users in Bangkok, Thailand.
AB  - BACKGROUND: Since 2003 Thailand has waged an aggressive "war on drugs" campaign
      focused on arresting and incarcerating suspected drug users and dealers. However,
      little is known about incarceration experiences among IDU in the wake of the
      recent war on drugs. Therefore, we sought to examine incarceration experiences
      among IDU in Bangkok, Thailand. METHODS: We examined the prevalence of
      incarceration among community-recruited IDU participating in the Mitsampan
      Community Research Project. Multivariate logistic regression was used to identify
      factors associated with a self-reported history of incarceration. We also
      examined the prevalence of injection drug use and syringe sharing within prisons.
      RESULTS: 252 IDU were recruited in August 2008; 66 (26.2%) were female and the
      median age was 36.5 years. In total, 197 (78.2%) participants reported a history
      of incarceration. In multivariate analyses, reporting a history of incarceration
      was associated with a history of compulsory drug treatment (adjusted odds ratio
      [AOR] = 4.93; 95% confidence interval [CI]: 1.95 - 12.48), non-fatal overdose
      (AOR = 3.69; 95%CI: 1.45 - 9.39), syringe sharing (AOR = 2.20; 95%CI: 1.12 -
      4.32), and female gender (AOR = 0.41; 95%CI: 0.20 - 0.82). Among those who
      reported a history of incarceration, 59 (29.9%) reported injection drug use in
      prison, and 48 (81.4%) of these individuals reported sharing syringes in prison.
      Incarceration was not associated with the number of injections performed in the
      previous week (p = 0.202). CONCLUSION: Over three-quarters of the IDU
      participating in this study reported a history of incarceration, and 30% of these
      individuals reported injection drug use within prison. Further, an alarmingly
      high level of syringe sharing within prison was reported, and incarceration was
      not associated with reductions in drug use. These findings provide further
      evidence of the need for community diversion strategies, as well as harm
      reduction programs, in Thai prisons.

PMID- 20042106
TI  - Fagerstrom test for nicotine dependence vs heavy smoking index in a general
      population survey.
AB  - BACKGROUND: The Fagerstrom Test for Nicotine Dependence (FTND) is used for
      assessing nicotine dependence. A shorter test derived from the FTND used for the
      general population is the Heavy Smoking Index (HSI) (six questions vs. two). The
      objective of this study is to compare the validity of the HSI versus the FTND.
      METHODS: A survey of tobacco use in the general population was carried out in the
      northern Spanish region of Galicia using both the FTND and the HSI to study a
      representative sample of 1655 daily smokers. The HSI was compared with the FTND,
      considered the gold standard. Measures of sensitivity, specificity and predictive
      values were calculated. Concordance between the tests was also established
      (Cohen's kappa). RESULTS: Cohen's kappa showed good agreement between measures
      (Kappa = 0.7); specificity values were also high (Sp = 96.2%). Sensitivity
      analysis in females (Se = 62.3%) did not show good agreement. CONCLUSIONS: The
      HSI can be used as a reasonably good screening test in order to identify daily
      smokers with high nicotine dependence. Nevertheless, for populations or
      subpopulations having low nicotine dependence, such as women, the FTND is more
      reliable.

PMID- 20042107
TI  - Virus infection elevates transcriptional activity of miR164a promoter in plants.
AB  - BACKGROUND: Micro RNAs (miRs) constitute a large group of endogenous small RNAs
      that have crucial roles in many important plant functions. Virus infection and
      transgenic expression of viral proteins alter accumulation and activity of miRs
      and so far, most of the published evidence involves post-transcriptional
      regulations. RESULTS: Using transgenic plants expressing a reporter gene under
      the promoter region of a characterized miR (P-miR164a), we monitored the reporter
      gene expression in different tissues and during Arabidopsis development. Strong
      expression was detected in both vascular tissues and hydathodes. P-miR164a
      activity was developmentally regulated in plants with a maximum expression at
      stages 1.12 to 5.1 (according to Boyes, 2001) along the transition from
      vegetative to reproductive growth. Upon quantification of P-miR164a-derived GUS
      activity after Tobacco mosaic virus Cg or Oilseed rape mosaic virus (ORMV)
      infection and after hormone treatments, we demonstrated that ORMV and gibberellic
      acid elevated P-miR164a activity. Accordingly, total mature miR164, precursor of
      miR164a and CUC1 mRNA (a miR164 target) levels increased after virus infection
      and interestingly the most severe virus (ORMV) produced the strongest promoter
      induction. CONCLUSION: This work shows for the first time that the alteration of
      miR pathways produced by viral infections possesses a transcriptional component.
      In addition, the degree of miR alteration correlates with virus severity since a
      more severe virus produces a stronger P-miR164a induction.

PMID- 20042108
TI  - The acidic domains of the Toc159 chloroplast preprotein receptor family are
      intrinsically disordered protein domains.
AB  - BACKGROUND: The Toc159 family of proteins serve as receptors for chloroplast
      destined preproteins. They directly bind to transit peptides, and exhibit
      preprotein substrate selectivity conferred by an unknown mechanism. The Toc159
      receptors each include three domains: C-terminal membrane, central GTPase, and N
      terminal acidic (A-) domains. Although the function(s) of the A-domain remains
      largely unknown, the amino acid sequences are most variable within these domains,
      suggesting they may contribute to the functional specificity of the receptors.
      RESULTS: The physicochemical properties of the A-domains are characteristic of
      intrinsically disordered proteins (IDPs). Using CD spectroscopy we show that the
      A-domains of two Arabidopsis Toc159 family members (atToc132 and atToc159) are
      disordered at physiological pH and temperature and undergo conformational changes
      at temperature and pH extremes that are characteristic of IDPs. CONCLUSIONS:
      Identification of the A-domains as IDPs will be important for determining their
      precise function(s), and suggests a role in protein-protein interactions, which
      may explain how these proteins serve as receptors for such a wide variety of
      preprotein substrates.

PMID- 20042109
TI  - Classification across gene expression microarray studies.
AB  - BACKGROUND: The increasing number of gene expression microarray studies
      represents an important resource in biomedical research. As a result, gene
      expression based diagnosis has entered clinical practice for patient
      stratification in breast cancer. However, the integration and combined analysis
      of microarray studies remains still a challenge. We assessed the potential
      benefit of data integration on the classification accuracy and systematically
      evaluated the generalization performance of selected methods on four breast
      cancer studies comprising almost 1000 independent samples. To this end, we
      introduced an evaluation framework which aims to establish good statistical
      practice and a graphical way to monitor differences. The classification goal was
      to correctly predict estrogen receptor status (negative/positive) and
      histological grade (low/high) of each tumor sample in an independent study which
      was not used for the training. For the classification we chose support vector
      machines (SVM), predictive analysis of microarrays (PAM), random forest (RF) and
      k-top scoring pairs (kTSP). Guided by considerations relevant for classification
      across studies we developed a generalization of kTSP which we evaluated in
      addition. Our derived version (DV) aims to improve the robustness of the
      intrinsic invariance of kTSP with respect to technologies and preprocessing.
      RESULTS: For each individual study the generalization error was benchmarked via
      complete cross-validation and was found to be similar for all classification
      methods. The misclassification rates were substantially higher in classification
      across studies, when each single study was used as an independent test set while
      all remaining studies were combined for the training of the classifier. However,
      with increasing number of independent microarray studies used in the training,
      the overall classification performance improved. DV performed better than the
      average and showed slightly less variance. In particular, the better predictive
      results of DV in across platform classification indicate higher robustness of the
      classifier when trained on single channel data and applied to gene expression
      ratios. CONCLUSIONS: We present a systematic evaluation of strategies for the
      integration of independent microarray studies in a classification task. Our
      findings in across studies classification may guide further research aiming on
      the construction of more robust and reliable methods for stratification and
      diagnosis in clinical practice.

PMID- 20042110
TI  - A curriculum to teach medical students to care for people with disabilities:
      development and initial implementation.
AB  - BACKGROUND: Lack of knowledge and skills, and negative attitudes towards patients
      with disabilities, may adversely affect the services available to this group and
      negatively affect their health outcomes. The objective of this paper is to
      describe the development and initial implementation of a curriculum for teaching
      medical students to care for patients with disabilities. METHODS: We followed the
      six-step approach for developing curricula for medical education: general needs
      assessment, specific needs assessment, defining goals and objectives, determining
      the educational strategies, planning the implementation, and developing an
      evaluation plan. RESULTS: The curriculum has well defined goals and objectives
      covering knowledge, attitudes and skills. It employs both traditional and non
      traditional teaching strategies. The implementation is planned over the four-year
      medical school curriculum in collaboration with a number of academic departments
      and specialized community-based agencies. The curriculum evaluation includes an
      attitudinal survey which is administered using a controlled design (pre- and post
      exposure to the curriculum). The initial implementation of the curriculum has
      been very successful. CONCLUSION: We have developed a longitudinal curriculum to
      teach medical students to care for people with disabilities. A rigorous
      evaluation of the impact of the curriculum is needed.

PMID- 20042111
TI  - T2 quantification for improved detection of myocardial edema.
AB  - BACKGROUND: T2-Weighted (T2W) magnetic resonance imaging (MRI) pulse sequences
      have been used to detect edema in patients with acute myocardial infarction and
      differentiate acute from chronic infarction. T2W sequences have suffered from
      several problems including (i) signal intensity variability caused by phased
      array coils, (ii) high signal from slow moving ventricular chamber blood that can
      mimic and mask elevated T2 in sub-endocardial myocardium, (iii) motion artifacts,
      and (iv) the subjective nature of T2W image interpretation. In this work we
      demonstrate the advantages of a quantitative T2 mapping technique to accurately
      and reliably detect regions of edematous myocardial tissue without the
      limitations of qualitative T2W imaging. METHODS: Methods of T2 mapping were
      evaluated on phantoms; the best of these protocols was then optimized for in vivo
      imaging. The optimized protocol was used to study the spatial, view-dependent,
      and inter-subject variability and motion sensitivity in healthy subjects. Using
      the insights gained from this, the utility of T2 mapping was demonstrated in a
      porcine model of acute myocardial infarction (AMI) and in three patients with
      AMI. RESULTS: T2-prepared SSFP demonstrated greater accuracy in estimating the T2
      of phantoms than multi-echo turbo spin echo. The T2 of human myocardium was found
      to be 52.18 +/- 3.4 ms (range: 48.96 ms to 55.67 ms), with variability between
      subjects unrelated to heart rate. Unlike T2W images, T2 maps did not show any
      signal variation due to the variable sensitivity of phased array coils and were
      insensitive to cardiac motion. In the three pigs and three patients with AMI, the
      T2 of the infarcted region was significantly higher than that of remote
      myocardium. CONCLUSION: Quantitative T2 mapping addresses the well-known problems
      associated with T2W imaging of the heart and offers the potential for increased
      accuracy in the detection of myocardial edema.

PMID- 20042112
TI  - Retroviral vectors encoding ADA regulatory locus control region provide enhanced
      T-cell-specific transgene expression.
AB  - BACKGROUND: Murine retroviral vectors have been used in several hundred gene
      therapy clinical trials, but have fallen out of favor for a number of reasons.
      One issue is that gene expression from viral or internal promoters is highly
      variable and essentially unregulated. Moreover, with retroviral vectors, gene
      expression is usually silenced over time. Mammalian genes, in contrast, are
      characterized by highly regulated, precise levels of expression in both a
      temporal and a cell-specific manner. To ascertain if recapitulation of endogenous
      adenosine deaminase (ADA) expression can be achieved in a vector construct we
      created a new series of Moloney murine leukemia virus (MuLV) based retroviral
      vector that carry human regulatory elements including combinations of the ADA
      promoter, the ADA locus control region (LCR), ADA introns and human
      polyadenylation sequences in a self-inactivating vector backbone. METHODS: A MuLV
      based retroviral vector with a self-inactivating (SIN) backbone, the
      phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein
      (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed
      from this basic vector by deletion or addition of certain elements. The added
      elements that were assessed are the human ADA promoter, human ADA locus control
      region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth
      hormone polyadenylation signal. Retroviral vector particles were produced by
      transient three-plasmid transfection of 293T cells. Retroviral vectors encoding
      eGFP were titered by transducing 293A cells, and then the proportion of GFP
      positive cells was determined using fluorescence-activated cell sorting (FACS).
      Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI)
      of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis
      using mean fluorescent intensity (MFI) detection. RESULTS: Vectors that contained
      the ADA LCR were preferentially expressed in T-cell lines. Further improvements
      in T-cell specific gene expression were observed with the incorporation of
      additional cis-regulatory elements, such as a human polyadenylation signal and
      intron 7 from the human ADA gene. CONCLUSION: These studies suggest that the
      combination of an authentically regulated ADA gene in a murine retroviral vector,
      together with additional locus-specific regulatory refinements, will yield a
      vector with a safer profile and greater efficacy in terms of high-level,
      therapeutic, regulated gene expression for the treatment of ADA-deficient severe
      combined immunodeficiency.

PMID- 20042113
TI  - MicroRNA and tasiRNA diversity in mature pollen of Arabidopsis thaliana.
AB  - BACKGROUND: New generation sequencing technology has allowed investigation of the
      small RNA populations of flowering plants at great depth. However, little is
      known about small RNAs in their reproductive cells, especially in post-meiotic
      cells of the gametophyte generation. Pollen - the male gametophyte - is the
      specialised haploid structure that generates and delivers the sperm cells to the
      female gametes at fertilisation. Whether development and differentiation of the
      male gametophyte depends on the action of microRNAs and trans-acting siRNAs
      guiding changes in gene expression is largely unknown. Here we have used 454
      sequencing to survey the various small RNA populations present in mature pollen
      of Arabidopsis thaliana. RESULTS: In this study we detected the presence of 33
      different microRNA families in mature pollen and validated the expression levels
      of 17 selected miRNAs by Q-RT-PCR. The majority of the selected miRNAs showed
      pollen-enriched expression compared with leaves. Furthermore, we report for the
      first time the presence of trans-acting siRNAs in pollen. In addition to
      describing new patterns of expression for known small RNAs in each of these
      classes, we identified 7 putative novel microRNAs. One of these, ath-MIR2939,
      targets a pollen-specific F-box transcript and we demonstrate cleavage of its
      target mRNA in mature pollen. CONCLUSIONS: Despite the apparent simplicity of the
      male gametophyte, comprising just two different cell types, pollen not only
      utilises many miRNAs and trans-acting siRNAs expressed in the somatic tissues but
      also expresses novel miRNAs.

PMID- 20042114
TI  - A laser pointer driven microheater for precise local heating and conditional gene
      regulation in vivo. Microheater driven gene regulation in zebrafish.
AB  - BACKGROUND: Tissue heating has been employed to study a variety of biological
      processes, including the study of genes that control embryonic development.
      Conditional regulation of gene expression is a particularly powerful approach for
      understanding gene function. One popular method for mis-expressing a gene of
      interest employs heat-inducible heat shock protein (hsp) promoters. Global heat
      shock of hsp-promoter-containing transgenic animals induces gene expression
      throughout all tissues, but does not allow for spatial control. Local heating
      allows for spatial control of hsp-promoter-driven transgenes, but methods for
      local heating are cumbersome and variably effective. RESULTS: We describe a
      simple, highly controllable, and versatile apparatus for heating biological
      tissue and other materials on the micron-scale. This microheater employs micron
      scale fiber optics and uses an inexpensive laser-pointer as a power source.
      Optical fibers can be pulled on a standard electrode puller to produce tips of
      varying sizes that can then be used to reliably heat 20-100 mum targets. We
      demonstrate precise spatiotemporal control of hsp70l:GFP transgene expression in
      a variety of tissue types in zebrafish embryos and larvae. We also show how this
      system can be employed as part of a new method for lineage tracing that would
      greatly facilitate the study of organogenesis and tissue regulation at any time
      in the life cycle. CONCLUSION: This versatile and simple local heater has broad
      utility for the study of gene function and for lineage tracing. This system could
      be used to control hsp-driven gene expression in any organism simply by bringing
      the fiber optic tip in contact with the tissue of interest. Beyond these uses for
      the study of gene function, this device has wide-ranging utility in materials
      science and could easily be adapted for therapeutic purposes in humans.

PMID- 20042115
TI  - Dynamic maps: a visual-analytic methodology for exploring spatio-temporal disease
      patterns.
AB  - BACKGROUND: Epidemiologic studies are often confounded by the human and
      environmental interactions that are complex and dynamic spatio-temporal
      processes. Hence, it is difficult to discover nuances in the data and generate
      pertinent hypotheses. Dynamic mapping, a method to simultaneously visualize
      temporal and spatial information, was introduced to elucidate such complexities.
      A conceptual framework for dynamic mapping regarding principles and
      implementation methods was proposed. METHODS: The spatio-temporal dynamics of
      Salmonella infections for 2002 in the U.S. elderly were depicted via dynamic
      mapping. Hospitalization records were obtained from the Centers of Medicare and
      Medicaid Services. To visualize the spatial relationship, hospitalization rates
      were computed and superimposed onto maps of environmental exposure factors
      including livestock densities and ambient temperatures. To visualize the temporal
      relationship, the resultant maps were composed into a movie. RESULTS: The dynamic
      maps revealed that the Salmonella infections peaked at specific spatio-temporal
      loci: more clusters were observed in the summer months and higher density of such
      clusters in the South. The peaks were reached when the average temperatures were
      greater than 83.4 degrees F (28.6 degrees C). Although the relationship of
      salmonellosis rates and occurrence of temperature anomalies was non-uniform, a
      strong synchronization was found between high broiler chicken sales and dense
      clusters of cases in the summer. CONCLUSIONS: Dynamic mapping is a practical
      visual-analytic technique for public health practitioners and has an outstanding
      potential in providing insights into spatio-temporal processes such as revealing
      outbreak origins, percolation and travelling waves of the diseases, peak timing
      of seasonal outbreaks, and persistence of disease clusters.

PMID- 20042116
TI  - Selective control of primer usage in multiplex one-step reverse transcription
      PCR.
AB  - BACKGROUND: Multiplex RT-PCR is a valuable technique used for pathogen
      identification, disease detection and relative quantification of gene expression.
      The simplification of this protocol into a one-step procedure saves time and
      reagents. However, intensive PCR optimization is often required to overcome
      competing undesired PCR primer extension during the RT step. RESULTS: Herein, we
      report multiplex one-step RT-PCR experiments in which the PCR primers contain
      thermolabile phosphotriester modification groups. The presence of these groups
      minimizes PCR primer extension during the RT step and allows for control of PCR
      primer extension until the more stringent, elevated temperatures of PCR are
      reached. Results reveal that the use of primers whose extension can be controlled
      in a temperature-mediated way provides improved one-step RT-PCR specificity in
      both singleplex and multiplex reaction formats. CONCLUSIONS: The need for an
      accurate and sensitive technique to quantify mRNA expression levels makes the
      described modified primer technology a promising tool for use in multiplex one
      step RT-PCR. A more accurate representation of the abundances in initial template
      sample is feasible with modified primers, as artifacts of biased PCR are reduced
      because of greater improvements in reaction specificity.

PMID- 20042117
TI  - Translating research into policy: lessons learned from eclampsia treatment and
      malaria control in three southern African countries.
AB  - BACKGROUND: Little is known about the process of knowledge translation in low-
      and middle-income countries. We studied policymaking processes in Mozambique,
      South Africa and Zimbabwe to understand the factors affecting the use of research
      evidence in national policy development, with a particular focus on the findings
      from randomized control trials (RCTs). We examined two cases: the use of
      magnesium sulphate (MgSO(4)) in the treatment of eclampsia in pregnancy (a
      clinical case); and the use of insecticide treated bed nets and indoor residual
      household spraying for malaria vector control (a public health case). METHODS: We
      used a qualitative case-study methodology to explore the policy making process.
      We carried out key informants interviews with a range of research and policy
      stakeholders in each country, reviewed documents and developed timelines of key
      events. Using an iterative approach, we undertook a thematic analysis of the
      data. FINDINGS: Prior experience of particular interventions, local champions,
      stakeholders and international networks, and the involvement of researchers in
      policy development were important in knowledge translation for both case studies.
      Key differences across the two case studies included the nature of the evidence,
      with clear evidence of efficacy for MgSO(4 )and ongoing debate regarding the
      efficacy of bed nets compared with spraying; local researcher involvement in
      international evidence production, which was stronger for MgSO(4 )than for
      malaria vector control; and a long-standing culture of evidence-based health care
      within obstetrics. Other differences were the importance of bureaucratic
      processes for clinical regulatory approval of MgSO(4), and regional networks and
      political interests for malaria control. In contrast to treatment policies for
      eclampsia, a diverse group of stakeholders with varied interests, differing in
      their use and interpretation of evidence, was involved in malaria policy
      decisions in the three countries. CONCLUSION: Translating research knowledge into
      policy is a complex and context sensitive process. Researchers aiming to enhance
      knowledge translation need to be aware of factors influencing the demand for
      different types of research; interact and work closely with key policy
      stakeholders, networks and local champions; and acknowledge the roles of
      important interest groups.

PMID- 20042118
TI  - The roles of EGF and Wnt signaling during patterning of the C. elegans
      Bgamma/delta Equivalence Group.
AB  - BACKGROUND: During development, different signaling pathways interact to specify
      cell fate by regulating transcription factors necessary for fate specification
      and morphogenesis. In Caenorhabditis elegans, the EGF-Ras and Wnt signaling
      pathways have been shown to interact to specify cell fate in three equivalence
      groups: the vulval precursor cells (VPCs), the hook competence group (HCG) and
      P11/12. In the VPCs, HCG and P11/12 pair, EGF and Wnt signaling positively
      regulate different Hox genes, each of which also functions during fate
      specification. In the male, EGF-Ras signaling is required to specify the Bgamma
      fate within the Bgamma/delta equivalence pair, while Notch signaling is required
      for Bdelta fate specification. In addition, TGF-beta signaling by dbl-1/dpp
      controls ceh-13/labial/Hox1 expression in Bgamma. RESULTS: We show that EGF-Ras
      signaling is required for Bgamma expression of ceh-13/labial/Hox1. The
      transcription factors lin-1/ETS and lin-31/Forkhead, functioning downstream of
      the EGF pathway, as well as sur-2/MED23 (a component of the Mediator complex)
      also control ceh-13 expression in Bgamma. In addition, our results indicate that
      lin-44/Wnt, mom-2/Wnt and lin-17/Fz are necessary to maintain the division of
      Bgamma along a longitudinal axis. We also show that dbl-1/dpp acts either in
      parallel or downstream of EGF pathway to regulate ceh-13/Hox1 expression in
      Bgamma. Lastly, we find that a dbl-1/dpp null mutation did not cause any vulval
      or P12 defects and did not enhance vulval and P12 defects of reduction-of
      function mutations of components of the EGF pathway. CONCLUSIONS: ceh
      13/labial/Hox1 expression in Bgamma is regulated by the EGF pathway and
      downstream factors lin-1/ETS lin-31/Forkhead and sur-2/MED23. Wnt signaling is
      required for proper Bgamma division, perhaps to orient the Bgamma mitotic
      spindle. Our results suggest that dbl-1/dpp is not required for VPC and P12
      specification, highlighting another difference among these EGF-dependent
      equivalence groups.

PMID- 20042119
TI  - Multilocus variable-number tandem repeat analysis for molecular typing and
      phylogenetic analysis of Shigella flexneri.
AB  - BACKGROUND: Shigella flexneri is one of the causative agents of shigellosis, a
      major cause of childhood mortality in developing countries. Multilocus variable
      number tandem repeat (VNTR) analysis (MLVA) is a prominent subtyping method to
      resolve closely related bacterial isolates for investigation of disease outbreaks
      and provide information for establishing phylogenetic patterns among isolates.
      The present study aimed to develop an MLVA method for S. flexneri and the VNTR
      loci identified were tested on 242 S. flexneri isolates to evaluate their
      variability in various serotypes. The isolates were also analyzed by pulsed-field
      gel electrophoresis (PFGE) to compare the discriminatory power and to evaluate
      the usefulness of MLVA as a tool for phylogenetic analysis of S. flexneri.
      RESULTS: Thirty-six VNTR loci were identified by exploring the repeat sequence
      loci in genomic sequences of Shigella species and by testing the loci on nine
      isolates of different subserotypes. The VNTR loci in different serotype groups
      differed greatly in their variability. The discriminatory power of an MLVA assay
      based on four most variable VNTR loci was higher, though not significantly, than
      PFGE for the total isolates, a panel of 2a isolates, which were relatively
      diverse, and a panel of 4a/Y isolates, which were closely-related. Phylogenetic
      groupings based on PFGE patterns and MLVA profiles were considerably concordant.
      The genetic relationships among the isolates were correlated with serotypes. The
      phylogenetic trees constructed using PFGE patterns and MLVA profiles presented
      two distinct clusters for the isolates of serotype 3 and one distinct cluster for
      each of the serotype groups, 1a/1b/NT, 2a/2b/X/NT, 4a/Y, and 6. Isolates that had
      different serotypes but had closer genetic relatedness than those with the same
      serotype were observed between serotype Y and subserotype 4a, serotype X and
      subserotype 2b, subserotype 1a and 1b, and subserotype 3a and 3b. CONCLUSIONS:
      The 36 VNTR loci identified exhibited considerably different degrees of
      variability among S. flexneri serotype groups. VNTR locus could be highly
      variable in a serotype but invariable in others. MLVA assay based on four highly
      variable loci could display a comparable resolving power to PFGE in
      discriminating isolates. MLVA is also a prominent molecular tool for phylogenetic
      analysis of S. flexneri; the resulting data are beneficial to establish clear
      clonal patterns among different serotype groups and to discern clonal groups
      among isolates within the same serotype. As highly variable VNTR loci could be
      serotype-specific, a common MLVA protocol that consists of only a small set of
      loci, for example four to eight loci, and that provides high resolving power to
      all S. flexneri serotypes may not be obtainable.

PMID- 20042120
TI  - Effects of chronic low dose rotenone treatment on human microglial cells.
AB  - BACKGROUND: Exposure to toxins/chemicals is considered to be a significant risk
      factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is
      the naturally occurring herbicide rotenone that is now used widely in
      establishing PD models. We, and others, have shown that chronic low dose rotenone
      treatment induces excessive accumulation of Reactive Oxygen Species (ROS),
      inclusion body formation and apoptosis in dopaminergic neurons of animal and
      human origin. Some studies have also suggested that microglia enhance the
      rotenone induced neurotoxicity. While the effects of rotenone on neurons are well
      established, there is little or no information available on the effect of
      rotenone on microglial cells, and especially cells of human origin. The aim of
      the present study was to investigate the effects of chronic low dose rotenone
      treatment on human microglial CHME-5 cells. METHODS: We have shown previously
      that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y
      cells and therefore used these cells as a control for inclusion body formation in
      this study. SH-SY5Y and CHME-5 cells were treated with 5 nM rotenone for four
      weeks. At the end of week 4, both cell types were analysed for the presence of
      inclusion bodies, superoxide dismutases and cell activation (only in CHME-5
      cells) using Haematoxylin and Eosin staining, immunocytochemical and western
      blotting methods. Levels of active caspases and ROS (both extra and intra
      cellular) were measured using biochemical methods. CONCLUSION: The results
      suggest that chronic low dose rotenone treatment activates human microglia (cell
      line) in a manner similar to microglia of animal origin as shown by others.
      However human microglia release excessive amounts of ROS extracellularly, do not
      show excessive amounts of intracellular ROS and active caspases and most
      importantly do not show any protein aggregation or inclusion body formation.
      Human microglia appear to be resistant to rotenone (chronic, low dose) induced
      damage.

PMID- 20042121
TI  - Excitatory and inhibitory effects of prolactin release activated by nerve
      stimulation in rat anterior pituitary.
AB  - BACKGROUND: A series of studies showed the presence of substantial amount of
      nerve fibers and their close relationship with the anterior pituitary gland
      cells. Our previous studies have suggested that aside from the classical theory
      of humoral regulation, the rat anterior pituitary has direct neural regulation on
      adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses
      are found on every type of the hormone-secreting cells, many on lactotrophs. The
      present study was aimed at investigating the physiological significance of this
      synaptic relationship on prolactin release. METHODS: The anterior pituitary of
      rat was sliced and stimulated with electrical field in a self-designed perfusion
      chamber. The perfusate was continuously collected in aliquots and measured by
      radioimmunoassay for prolactin levels. After statistic analysis, differences of
      prolactin concentrations within and between groups were outlined. RESULTS: The
      results showed that stimulation at frequency of 2 Hz caused a quick enhancement
      of prolactin release, when stimulated at 10 Hz, prolactin release was found to be
      inhibited which came slower and lasted longer. The effect of nerve stimulation on
      prolactin release is diphasic and frequency dependent. CONCLUSIONS: The present
      in vitro study offers the first physiological evidence that stimulation of nerve
      fibers can affect prolactin release in rat anterior pituitary. Low frequency
      stimulation enhances prolactin release and high frequency mainly inhibits it.

PMID- 20042122
TI  - Regulation of Akt(ser473) phosphorylation by choline kinase in breast carcinoma
      cells.
AB  - BACKGROUND: The serine/threonine kinase PKB/Akt plays essential role in various
      cellular processes including cell growth and proliferation, metabolism and cell
      survival. The importance of the Akt pathway is highlighted by the mutation of
      various components of the pathway such as the PTEN and PI3-kinase (P110alpha) in
      human cancers. In this paper, we employed an RNA interference library targeting
      all human kinases to screen for kinases involved in the regulation of Akt
      activation, in particular serine 473 phosphorylation. Here, we transfected the
      MDA-MB 468 breast cell line with the human kinome siRNA library and measured Akt
      activation using an antibody specific for phosphoserine 473 of Akt. RESULTS: The
      screen revealed that phosphorylation of Akt(ser473) can be regulated by more than
      90 kinases. Interestingly, phosphorylation of Akt(ser473), but not thr308, can be
      severely reduced by inhibition of Choline kinase activity via siRNA or small
      molecule inhibitors. We show here that the regulation of Akt phosphorylation by
      Choline kinase is PI3K-independent. In addition, xenograft tumors treated with
      Choline kinase inhibitors demonstrated a statistically significant decrease in
      Akt(ser473) phosphorylation. Importantly, the reduction in phosphorylation
      correlates with regression of these xenograft tumors in the mouse model.
      CONCLUSION: High Choline kinase expression and activity has previously been
      implicated in tumor development and metastasis. The mechanism by which Choline
      kinase is involved in tumor formation is still not fully resolved. From our data,
      we proposed that Choline kinase plays a key role in regulating Akt(ser473)
      phosphorylation, thereby promoting cell survival and proliferation.

PMID- 20042124
TI  - 3D-conformal accelerated partial breast irradiation treatment planning: the value
      of surgical clips in the delineation of the lumpectomy cavity.
AB  - BACKGROUND: Accurate localisation of the lumpectomy cavity (LC) volume is one of
      the most critical points in 3D-conformal Partial breast irradiation (3D-APBI)
      treatment planning because the irradiated volume is restricted to a small breast
      volume. Here, we studied the role of the placement of surgical clips at the 4
      cardinal points of the lumpectomy cavity in target delineation. METHODS: Forty CT
      based 3D-APBI plans were retrieved on which a total of 4 radiation oncologists,
      two trainee and two experienced physicians, outlined the lumpectomy cavity. The
      inter-observer variability of LC contouring was assessed when the CTV was defined
      as the delineation that encompassed both surgical clips and remodelled breast
      tissue. RESULTS: The conformity index of tumour bed delineation was significantly
      improved by the placement of surgical clips within the LC (median at 0.65).
      Furthermore, a better conformity index of LC was observed according to the
      experience of the physicians (median CI = 0.55 for trainee physicians vs 0.65 for
      experienced physicians). CONCLUSIONS: The placement of surgical clips improved
      the accuracy of lumpectomy cavity delineation in 3D-APBI. However, a learning
      curve is needed to improve the conformity index of the lumpectomy cavity.

PMID- 20042123
TI  - A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium
      falciparum.
AB  - BACKGROUND: Plasmodium parasites are causative agents of malaria which affects
      >500 million people and claims approximately 2 million lives annually. The
      completion of Plasmodium genome sequencing and availability of PlasmoDB database
      has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA
      synthetases (aaRSs) are pivotal enzymes for protein translation and other vital
      cellular processes. We report an extensive analysis of the Plasmodium falciparum
      genome to identify and classify aaRSs in this organism. RESULTS: Using various
      computational and bioinformatics tools, we have identified 37 aaRSs in P.
      falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs
      in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37
      Pf-aaRS sequences contain signal peptides possibly directing them to different
      cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at
      various life cycle stages of the parasite; (iv) several PfaaRSs posses very
      unusual domain architectures; (v) phylogenetic analyses reveal evolutionary
      relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three
      dimensional structural modelling has provided insights which could be exploited
      in inhibitor discovery against parasite aaRSs. CONCLUSION: We have identified 37
      Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique
      attributes in this protein family. We have annotated all 37 Pf-aaRSs based on
      predicted localization, phylogenetics, domain architectures and their overall
      protein expression profiles. The sets of distinct features elaborated in this
      work will provide a platform for experimental dissection of this family of
      enzymes, possibly for the discovery of novel drugs against malaria.

PMID- 20042127
TI  - Laparoscopic Cholecystectomy in Elderly Patients.
AB  - [no abstract].

PMID- 20042125
TI  - Laparoscopic total extraperitoneal repair in femoral hernia without fixation of
      the mesh.
AB  - BACKGROUND AND OBJECTIVES: We report on laparoscopic total extraperitoneal repair
      without fixation of mesh for femoral hernia in 6 patients. METHODS: During a 3
      year period, laparoscopic total extraperitoneal repair of femoral hernia was
      performed without mesh fixation in 6 patients. The recurrence rate, pain scores,
      hospital stay, and other morbidity parameters were noted. Pain scores were 1=no
      pain, 2=mild pain, 3=moderate pain, 4=severe pain, and 5=intolerable pain.
      RESULTS: All 6 patients were females and had unilateral hernias. Mean age was
      33.8+/-18.6 years, and follow-up ranged from 12 months to 36 months. Four
      patients were operated on while under spinal anesthesia, and 2 patients were
      operated on while under general anesthesia. Mean operating time was 29.2+/-10.7
      minutes. The mean pain scores 24 hours and the first week after operation were,
      respectively, 2.33+/-0.52 and 1.33+/-0.52. Mean hospital stay was 1.17+/-0.41
      days, and mean days to resumption of normal activities were 8.5+/-2.1 days. No
      patient had urinary retention or seroma formation in the postoperative period. At
      follow-up, no hernia had recurred. CONCLUSIONS: Laparoscopic femoral hernia
      repair without fixing the mesh is safe, feasible, and associated with minimal
      morbidity and recurrence rates.

PMID- 20042126
TI  - Aberrant presentation of the gallbladder during laparoscopic cholecystectomy.
AB  - BACKGROUND: Aberrant gallbladder transposed to the left side is a rare congenital
      anomaly that has been seen in as many as 0.7% of the population. These
      gallbladders are situated under the left lobe of the liver between Segment III
      and IV and to the left of the falciform ligament. Many preoperative studies fail
      to identify the anomaly, causing confusion to the surgeon during laparoscopic
      resection. Selective use of intraoperative cholangiography and meticulous
      dissection can aid in safe resection. METHODS: A 61-year-old female was admitted
      with ultrasound confirmation of cholecystitis and subsequently taken to the
      operating room for a laparoscopic cholecystectomy. RESULTS: Evaluation of the
      gallbladder under laparoscopic view revealed an inflamed left aberrant
      gallbladder. An intraoperative cholangiogram was obtained to delineate the
      biliary anatomy that showed the cystic duct entering the common hepatic duct on
      the right side. CONCLUSION: A left aberrant gallbladder is a rare presentation
      that requires awareness of biliary anatomy and selective use of intraoperative
      cholangiography to aid in the safe laparoscopic resection of the gallbladder.

PMID- 20042128
TI  - Laparoscopic transumbilical cholecystectomy: surgical technique.
AB  - BACKGROUND: Laparoscopic cholecystectomy is generally performed using 4 ports by
      transperitoneal access. Recent developments regarding laparoscopic surgery have
      been directed toward reducing the size or number of ports to achieve the goal of
      minimally invasive surgery, by minilaparoscopy, natural orifice access, and the
      transumbilical approach. The aim of this article is to describe our laparoscopic
      transumbilical cholecystectomy technique using conventional laparoscopic
      instruments and ports. METHODS: The Veress needle was placed through the
      umbilicus, which allowed carbon dioxide inflow. A 5-mm trocar was placed in the
      periumbilical site for the laparoscope followed by the placement of 2 additional
      5-mm periumbilical trocars. The entire procedure was performed using conventional
      laparoscopic instruments. At the end of the surgery, trocars were removed, and
      all 3 periumbilical skin incisions were united for specimen retrieval. RESULTS:
      Five transumbilical cholecystectomies were performed following this technique.
      The mean BMI was 26.6 kg/m(2). The mean operative time and blood loss were 46.2
      minutes and 55 mL, respectively. No intraoperative complications occurred.
      Analgesia was performed using dipyrone (1g IV q6h) and ketoprofen (100 mg IV q12
      h). Time to first oral intake was 8 hours. Mean hospital stay was 19.2 hours.
      CONCLUSION: Laparoscopic transumbilical cholecystectomy seems to be feasible even
      using conventional laparoscopic instruments and can be considered a potential
      alternative for traditional laparoscopic cholecystectomy.

PMID- 20042129
TI  - The learning curve for robot-assisted radical cystectomy.
AB  - OBJECTIVE: Robot-assisted radical cystectomy has the potential to cure patients
      from bladder cancer while offering the benefits of minimally invasive surgery. We
      sought to evaluate the learning curve for this technically demanding procedure.
      MATERIALS AND METHODS: Robot-assisted radical cystectomy was attempted in 100
      consecutive patients. An IRB-approved review of our robot-assisted radical
      cystectomy database was conducted. Total operative (OR) time, cystectomy time,
      pelvic lymph node dissection (PLND) time, estimated blood loss (EBL), margin
      positivity, complications, and length of hospital stay were compared among
      patients divided into 4 cohorts of increasing surgical experience. Scattergrams
      and continuous curves were plotted to develop a robotic cystectomy learning
      curve. RESULTS: Overall OR time decreased from 375 minutes in cohort 1 to 352
      minutes in cohort 4, with less than 1% change in OR time after case 16. Time from
      incision to bladder extirpation decreased from 187 minutes in cohort one to 165
      minutes in cohort 4. Time for PLND increased from 44 minutes in cohort 1 to 77
      minutes in cohort 4. Lymph node yield increased from 14 nodes in cohort 1 to 23
      nodes in cohort 4. Positive surgical margins decreased from 4 patients in cohort
      1 to 0 patient in cohort 4. The complication rate had no change from 9 patients
      in cohort 1 to 9 patients in cohort 4. CONCLUSION: Operative results and
      oncologic outcomes for robot-assisted radical cystectomy constantly improve as
      the technique evolves.

PMID- 20042130
TI  - Single access laparoscopic splenectomy.
AB  - BACKGROUND: Laparoscopic splenectomy has been performed in a standard fashion
      with 4 to 5 trocars since the early 1990s. Single access laparoscopy has recently
      gained interest, but single access laparoscopic splenectomy has not been reported
      to date. It has the possible benefits of less pain, faster recovery, better
      cosmesis, with theoretically similar costs to that of traditional trocars.
      METHODS: A case is presented and the surgical technique of single access
      laparoscopic splenectomy is detailed. RESULTS: The patient is an otherwise
      healthy 24-year-old male with medically refractory idiopathic thrombocytopenic
      purpura and a platelet count of 15 000. A splenectomy was performed using a
      single incision laparoscopic technique. The patient was placed in a right lateral
      decubitus position, and a 2.5-cm left upper quadrant incision was made. A multi
      instrument flexible single incision port was used that held 3 trocars. A standard
      splenectomy was performed through this port. A linear stapler was used to
      transect the splenic hilum. The procedure time was just over 2 hours. The patient
      did well, was happy with his incision, and was discharged with a platelet count
      of 108 000. CONCLUSIONS: Single access laparoscopic splenectomy is feasible in
      select patients and may provide a less painful, better cosmetic result.

PMID- 20042131
TI  - [Several controversial problems during treatment of capillary leak syndrome].

PMID- 20042132
TI  - [What shall we do to advance the sepsis guidelines popularization?].

PMID- 20042133
TI  - [Effect of mesenteric lymph duct ligation on coagulability of blood after acute
      loss of blood in rats].
AB  - OBJECTIVE: To observe the effects of mesenteric lymph duct ligation on platelet
      function, thrombus formation in vitro and coagulation function in rats with acute
      loss of blood, and investigate the role of intestinal lymphatic pathway on
      coagulability change during acute loss of blood. METHODS: Twenty male Wistar rats
      were randomly divided into loss of blood group (n=10) and ligation group (n=10).
      The acute loss of blood model was reproduced by withdrawing blood (one fourth of
      body whole blood volume) with an automatic withdrawal-infusion machine through
      right common carotid artery. In ligation group, the mesenteric lymph duct was
      ligated after loss of blood, and in loss of blood group only a thread was passed
      under the mesenteric lymph duct. The rats' survival rate at 24 hours was
      recorded. After 24 hours, surviving rats were anesthetized again, and 6 ml of
      blood was with drew from left common carotid artery rapidly. The platelet
      adhesive rate, platelet aggregation rate, thrombus formation in vitro,
      coagulation function were determined before and after experiment, and the
      cerebral blood flow was measured. RESULTS: There were 6 rats alive in loss of
      blood group (60%), and 9 rats alive in ligation group (90%). The platelet
      adhesive rate, platelet aggregation rate, fibrinogen (Fib) content were increased
      in both groups, and cerebral blood flow was lower compared with before experiment
      significantly. The activated partial thromboplastin time (APTT) in loss of blood
      group, and thrombin time (TT) in both groups were prolonged. And the length of
      wet thrombus, wet weight of thrombus, length of dry thrombus, dry weight of
      thrombus and thrombus formation rate in loss of blood group were significantly
      increased compared with before experiment (P<0.05 or P<0.01). But in ligation
      group, the platelet adhesive rate [(15.02+/-1.24)%], platelet aggregation rate
      (at 1 minute, 3 minutes and max aggregation rate), length of wet thrombus, wet
      weight of thrombus, length of dry thrombus, dry weight of thrombus, thrombus
      formation rate [(46.2+/-6.9)%], APTT [(21.04+/-5.53)s] and Fib content [(433.67+/
      13.97) g/L] were lower, cerebral blood flow [(485.1+/-41.4) ml x kg(-1) x min(
      1)] was higher compared with loss of blood group, respectively [(18.54+/-1.18)%,
      (69.8+/-6.9)%, (26.35+/-6.26)s, (510.96+/-35.59) g/L, (417.8+/-42.2) ml x kg(-1)
      x min(-1), P<0.05 or P<0.01]. CONCLUSION: The results indicate that acute loss of
      blood leads to coagulation and increased thrombosis, and mesenteric lymph duct
      ligation can improve hypercoagulability of blood.

PMID- 20042134
TI  - [Effect of erythropoietin on the caspase-3 subfamily in preventing apoptosis of
      endothelial cell].
AB  - OBJECTIVE: To explore effect of erythropoietin on the caspase-3 subfamily in
      preventing apoptosis of human umbilical vein endothelial cells (HUVECs) induced
      by oxidized-low density lipoprotein (ox-LDL). METHODS: Third-sixth passages of
      HUVECs were used. Two experiments were conducted. In the first experiment, there
      was a blank control group, ox-LDL control group (100 mg/L, incubated for 48
      hours), and low, medium, and high recombinant human erythropoietin (rhEPO) groups
      (6.25, 25.00, 100.00 kU/L rhEPO incubated for 24 hours+100 mg/L ox-LDL incubated
      for 48 hours). Another experimental protocol consisted of groups of the cells
      pretreated with either caspase-3 inhibitor DEVD-CHO, or caspase-8 inhibitor z
      IETD-fmk, or caspase-9 inhibitor z-LEHD-fmk of 25 micromol/L for 24 hours, then
      HUVECs were exposed ox-LDL (100 mg/L) incubated for 48 hours. The activity of
      caspase-3, caspase-8, or caspase 9 was determined by caspase colorimetric assay.
      The cell survival rate was assessed with methyl thiazolyl tetrazolium (MTT)
      method. The positive expression rate of caspase-3 and apoptotic rate were
      measured by flow cytometer. RESULTS: The activity of caspase-3 was significantly
      decreased and cell survival rate was increased in the caspase-3 inhibitor group
      (both P<0.05). The activity of caspase-8 was decreased in the caspase-8 inhibitor
      group (P<0.05), but the cell survival rate was not significantly different from
      that of ox-LDL group (P>0.05). The activity of caspase-3 or caspase-9 was lower
      and cell survival rate was higher in the caspase-9 inhibitor group than that of
      ox-LDL group (all P<0.05). The pretreatment with rhEPO led to decreased activity
      of caspase-3, caspase-9, positive expression rate of caspase-3 and apoptotic rate
      in a dose-dependent manner compared with ox-LDL group (all P<0.05), but the
      activity of caspase-8 showed no significant difference from rhEPO pretreatment
      groups (all P>0.05). CONCLUSION: These results demonstrate that rhEPO can
      significantly inhibit the activity of caspase-3 or caspase-9 in endothelial cell
      apoptosis in a dose-dependent manner. Activation of caspase-3 or caspase-9 is
      involved in ox-LDL-induced HUVECs apoptotic signaling pathway, but caspase-8 is
      not involved.

PMID- 20042135
TI  - [A comparison of severity of illness scoring system for emergency department
      patients with systemic inflammatory response syndrome].
AB  - OBJECTIVE: To evaluate the predictive ability of 3 scoring systems, i.e. acute
      physiology and chronic health evaluation II (APACHE II) score, simplified acute
      physiology score II (SAPS II) and mortality in emergency department sepsis (MEDS)
      score in patients presenting systemic inflammatory response syndrome (SIRS) in
      emergency department. METHODS: Six hundred and twenty-one adult patients with
      SIRS admitted from December 2006 to September 2007 in the emergency department of
      Beijing Chaoyang Hospital were eligible for the study. The first 24-hour
      admission data necessary for the calculation of APACHE II score, SAPS II score,
      MEDS score and basic demographic statistics were collected and the outcomes in 28
      days were recorded. Logistic regression analysis was used to determine the
      independent predictors for 28-day mortality. Discrimination of each scoring
      system was assessed with the areas under the receiver operating characteristics
      (ROC) curve (AUC). RESULTS: A total of 222 patients died in 28 days in a total of
      621 patients. The age and mean levels of 3 scoring systems were predominantly
      higher in nonsurvivors than survivors (73 years vs. 70 years for age, P<0.05; 18
      vs. 14 for APACHE II score, P<0.01; 36 vs. 24 for SAPS II score, P<0.01; 14 vs. 7
      for MEDS score, P<0.01). The independent predictors of 28-day mortality were
      APACHE II score, SAPS II score and MEDS score. The AUCs were 0.715, 0.774 and
      0.965 for APACHE II score, SAPS II score and MEDS score, respectively. There was
      significant difference between MEDS score and APACHE II score in AUC (Z=35.435,
      P<0.01). CONCLUSION: In emergency department patients with SIRS, the MEDS score
      possesses more predictive ability than APACHE II score.

PMID- 20042136
TI  - [Effects of hydrocortisone on myocardial function in early stage of sepsis in
      rabbits].
AB  - OBJECTIVE: To study the effects of different dose of hydrocortisone (HC) on
      myocardial function in early stage of sepsis in rabbits. METHODS: Twenty-four
      male rabbits were randomly divided into three groups: model group (n=8), HC low
      dosage group (10 mg/kg, n=8), HC high dosage group (100 mg/kg, n=8). The model
      was reproduced by cecal ligation and puncture (CLP). The function of the left
      ventricle was monitored and blood was drawn at 5 time points [before CLP, before
      treatment (1 hour after CLP) and 2, 4, 6 hours after the treatment] to determine
      concentrations of cardiac troponin I (cTnI) and nitric oxide (NO). The expression
      of inducible nitric oxide synthase (iNOS) of myocytes was investigated. RESULTS:
      Compared to the basic levels, maximal positive and negative change in filling
      pressure versus time (+/-dp/dt max) decreased significantly, while NO increased
      significantly before treatment in all groups (all P<0.05). At 6 hours after
      treatment, +/-dp/dt max in HC low dosage group was significantly higher than that
      in the other two groups, while cTnI was significantly lower in HC low dosage
      group than that in the other two groups (all P<0.05). NO content in two HC groups
      was significantly lower than that in model group (all P<0.05), and the iNOS
      expressions on myocardial cells was weaker than model group [model group: (81.8+/
      15.8)%, HC low dosage group: (56.7+/-21.2)%, HC high dosage group: (54.6+/
      16.1)%, all P<0.05]. CONCLUSION: Myocardial function is remarkably damaged in
      rabbits with sepsis. HC low dosage group exerts protective effect on myocardial
      cells in early stage of sepsis.

PMID- 20042137
TI  - [A study on the active efflux system in methicillin-resistant Staphylococcus
      aureus].
AB  - OBJECTIVE: To explore the status of methicillin-resistant Staphylococcus aureus
      (MRSA) infection in an intensive care unit (ICU), and investigate the active
      efflux mechanism of MRSA. METHODS: Eighty isolates were identified as MRSA among
      102 strains of Staphylococcus aureus collected, and then the minimal inhibitory
      concentration (MIC) were determined. The 4 primers of active efflux gene were
      designed to amplify the 80 clinical isolates respectively by polymerase chain
      reaction (PCR). The PCR products were analyzed by electrophoresis in order to
      grasp the situation of the existence of the four genes (norA, qacA, qacB and
      qacJ). Omeprazole inhibition test was used to observe the changes in the
      susceptibility of MRSA to antibiotics. RESULTS: The detection rate of MRSA was
      78.4%. The sensitivity rate of MRSA to both vancomycin and teicoplanin was
      100.0%, while to other antibiotics (oxacillin, benzylpenicillin, cefuroxime,
      cefotaxime, ceftazidime, ceftiaxone, cefepime, cefoxitin, imipenem, piperacillin
      and tazobactam, azithromycin, erythromycin, chloramphenicol, clindamycin,
      amikacin, gentamicin, levofloxacin, gatifloxacin, ciprofloxacin) MRSA was multi
      drug resistant. The detection rates of norA, qacA, qacB and qacJ were 67.5%
      (54/80), 15.0% (12/80), 21.2% (17/80) and 11.2% (9/80), respectively. Combined
      use of omeprazole and levofloxacin could lower MIC value. CONCLUSION: The
      infection of MRSA in ICU is serious. MRSA is multi-drug resistant and possesses
      active efflux genes norA, qacA, qacB and qacJ. Omeprazole can inhibit the
      activity of the active efflux genes.

PMID- 20042138
TI  - [Study on apoptosis of splenic lymphocytes in rats with sepsis].
AB  - OBJECTIVE: To observe the change in number of spleen T lymphocytes and B
      lymphocytes and apoptosis of splenocytes in rats with sepsis, and explore the
      mechanism of immune imbalance in sepsis. METHODS: Eighty healthy male Wistar rats
      were randomly divided into two groups: sham operation (n=30) and sepsis model
      (n=50). Sepsis model was reproduced by cecal ligation and puncture (CLP). The
      rats were sacrificed and their spleens were obtained at 6, 12, 24, 48, 96 hours
      after the model was reproduced. The pathological changes in spleen were observed
      by optical microscopy. Immunohistochemistry method was used to examine the
      positive expression of CD4(+)/CD8(+)T lymphocyte and B lymphocyte, Bax and Bcl-2.
      Apoptotic cells of spleen were detected by means of terminal deoxynucleotidyl
      transferase mediated dUTP nick end labeling (TUNEL). RESULTS: By optical
      microscopy, white pulps were atrophied and splenic nodules were destroyed after
      CLP. At 6, 12, 24, 48, 96 hours after CLP, the number of CD(+)T lymphocyte, B
      lymphocyte and Bcl-2 positive expressed cells in sepsis model group were
      obviously reduced as compared with sham operation group (all P<0.01). CD8(+)
      positive lymphocytes were not significant changed (all P>0.05). Apoptotic
      splenocytes and Bax positive cells were obviously increased compared with those
      of sham operation group (all P<0.01). Correlation analysis showed that Bcl-2
      expression and cell apoptosis was negatively correlated (r=-0.659, P<0.01), but
      Bax positive cells and apoptosis showed positive correlation (r=0.522, P<0.01).
      CONCLUSION: Disturbance of immunological function exists in the rats with sepsis
      at 24 hours after CLP. The number of CD4(+) T lymphocyte, B lymphocyte was
      obviously reduced, apoptotic splenocytes were obviously increased. Bax and Bcl-2
      play an important role in apoptosis of splenocytes in sepsis.

PMID- 20042139
TI  - [Isolation of human pluripotent mesenchymal stem cells from second-trimester
      amniotic fluid using two kinds of culture protocol and their differentiation into
      neuron-like cells].
AB  - OBJECTIVE: To isolate mesenchymal stem cells (MSCs) from second-trimester
      amniotic fluid using an improved two-stage culture protocol, and to induce these
      MSCs into neuron-like cells. METHODS: An improved two-stage culture protocol for
      MSCs from amniotic fluid was developed. MSCs from amniotic fluid were induced to
      differentiate with beta-mercaptoethanol into neuron-like cells. Flow cytometry,
      reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry
      were employed for analysis of the phenotypic characteristics of the cultured MSCs
      from amniotic fluid. RESULTS: MSCs from amniotic fluid were successfully
      isolated, cultured and enriched without interfering with the routine process of
      fetal karyotyping. Flow cytometry analysis showed that they were positive for
      CD44, CD29, and CD105, but negative for CD45, CD34, or human leucocyte antigen-DR
      (HLA-DR). Importantly, a subpopulation of transcription factor Oct-4 positive
      cells could be detectable in the cultured MSCs from amniotic fluid. Moreover,
      MSCs from amniotic fluid obtained by two-stage culture protocol showed higher
      proliferation rate [(15.0+/-2.3)% vs. (10.0+/-1.8)%] and higher Oct-4 positive
      cell rate [(1.2+/-0.3)% vs. (0.9+/-0.2)%, both P<0.05]. After the induction, MSCs
      from amniotic fluid displayed processes that formed extensive networks. Positive
      cells for neurone specific enolase (NSE) constituted (54.76+/-3.65)%, and glial
      fibrillary acidic protein (GFAP) (36.28+/-4.27)%, respectively. CONCLUSION: We
      demonstrate that human pluripotent MSCs are present in second-trimester amniotic
      fluid. The two-stage culture protocol could be a kind of simple one with high
      performance and it does not interfere with the routine fetal karyotyping. MSCs
      from amniotic fluid can be induced to differentiate into neuron-like cells in
      vitro by beta-mercaptoethanol in optimal medium.

PMID- 20042140
TI  - [Study on dynamic changes in coagulability and von Willebrand factor and its
      correlation with prognosis of cardiopulmonary resuscitation].
AB  - OBJECTIVE: To investigate dynamic changes in coagulability and von Willebrand
      factor (vWF), and explore their correlation with prognosis of cardiopulmonary
      resuscitation (CPR). METHODS: Fifty CPR patients were divided into three groups
      according to the outcome. A group: 25 patients with successful recovery in the
      initial stage with restoration of spontaneous circulation (ROSC) lasting at least
      for 72 hours, but died ultimately; B group: 10 patients with successful recovery
      and finally survived; C group: the control group, 15 patients who died or ROSC<2
      hours after CPR. In the course of CPR, dynamic changes in prothrombin time (PT),
      activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen
      (Fg), platelet count (PLT), D-dimer, antithrombin III (AT III) and vWF were
      determined at the time of CPR, 24, 48 and 72 hours after ROSC. RESULTS: During
      CPR, the levels of PT, APTT, TT, D-dimer and vWF were higher, and the levels of
      Fg, PLT and AT III were lower in group C compared with groups A and B (all
      P<0.01). There was no significant difference between groups A and B (all P>0.05).
      In groups A and B, the levels of PT, APTT, TT, D-dimer and vWF increased and the
      levels of Fg, PLT, AT III decreased 24 hours after ROSC. The changes in all
      parameters reached peak or valley point at ROSC 48 hours (P<0.05 or P<0.01). At
      ROSC 72 hours all parameters were improved more obviously in group B (all
      P<0.01), but not improved in group A (all P>0.05). The levels of PT, APTT, TT, D
      dimer and vWF were much higher and the levels of Fg, PLT and AT III were much
      lower in group A than in group B (P<0.05 or P<0.01). CONCLUSION: Tissue and
      vascular endothelial injury, endogenous and extrinsic coagulation disorder and
      fibrinolytic dysfunction are found in the patients undergoing CPR. Their dynamic
      changes are observed in the course of CPR, and they are valuable in assessing the
      severity of patients' condition and prognosis.

PMID- 20042141
TI  - [Vicissitude of antibiotic sensitivity of Gram negative bacilli in patients with
      infection in emergency departments in Beijing during 2005 to 2007].
AB  - OBJECTIVE: To investigate changes in antibiotic sensitivity of Gram negative
      bacilli infections among emergency patients in large hospitals in Beijing during
      2005 to 2007. METHODS: Retrospective analysis of all the identified strains of
      Gram negative bacilli, and their sensitivity to antibiotic obtained in the
      emergency departments of 5 top first-class hospitals in Beijing for recent 3
      years. RESULTS: Two thousand two hundred and eighty-five strains of Gram negative
      bacilli had taken 64.62% of all, the priority 5 of which were Pseudomonas
      aeruginosa (23.89%), Escherichia coli (19.91%), Acinetobacter baumanii (17.59%),
      Klebsiella pneumoniae (8.05%) and Staphylococcus maltophilia (3.94%). The
      sensitivity of commonly used antibiotics plummeted greatly in recent 3 years,
      especially carbapenems, cephalosporins and quinolones. The resistance of imipenem
      resistant Pseudomonas aeruginosa was 17.30%, 22.53%, 31.92% respectively. The
      resistance of imipenem-resistant Acinetobacter baumanii was 13.87%, 12.09%,
      23.56% respectively. CONCLUSION: Infectious bacteria in emergency departments in
      Beijing top first-class hospitals tend to show the characteristics of hospital
      infection. In recent years, the sensitivity of bacilli to antibiotic has dropped
      greatly. The situation of antibiotics resistance might be depressed.

PMID- 20042142
TI  - [Clinical observation of early goal-directed therapy in patients with septic
      shock].

PMID- 20042143
TI  - [The protective effect of ulinastatin on the small intestine in rats with sepsis
      and its mechanism].

PMID- 20042144
TI  - [The protective effect of edaravone on the treatment of sepsis in rats].

PMID- 20042146
TI  - [Intensive insulin therapy in critically ill patients: new evaluation and new
      perception].

PMID- 20042147
TI  - [Advances in the study of the mechanism and the treatment for muscle wasting in
      sepsis].

PMID- 20042148
TI  - [Advances in the diagnosis and treatment of invasive candida infection in
      critically ill patients].

PMID- 20042149
TI  - Dental clinic as a health centre for screening of undiagnosed diabetes.

PMID- 20042150
TI  - Diltiazem (2%) versus glyceryl trinitrate cream (0.2%) in the management of
      chronic anal fissure.
AB  - OBJECTIVE: To assess and compare the effectiveness of topical 0.2% glycerl
      trinitrate (GTN) and topical 2% diltiazem (DTZ), in the management of chronic
      anal fissure. STUDY DESIGN: Comparative, descriptive study. PLACE AND DURATION OF
      STUDY: Department of Surgery, Liaquat University of Medical and Health Sciences,
      Jamshoro/Hyderabad from September 2004 to August 2005. METHODOLOGY: Patients with
      chronic anal fissure were treated with topical 0.2% GTN (50 patients) and 2% DTZ
      (47 patients) application for 8 weeks, three times a day at peri anal area.
      Symtoms, recurrence, wound healing and side effects were compared. Data was
      analyzed using SPSS version 10 employing X2 test. A p-value below 0.05 were
      considered statistically significant. RESULTS: There were 53 females and 44 males
      with a mean age of 30 years. Patients who received topical diltiazem (DTZ) showed
      statistically significant difference than those who were prescribed topical
      glycerl trinitrate terms of wound healing and side effects mainly the headaches
      (p=0.02 and 0.003 respectively). Improvement in symptoms (p=0.345) and recurrence
      rates (p=0.612) turned to be statistically insignificant although recurrence rate
      was lower with DTZ. CONCLUSION: Chemical sphincterotomy is an effective first
      line management for chronic anal fissure. Both GTN and DTZ are equally effective
      in managing the chronic anal fissure. DTZ has fewer side effects, a better
      healing response and low recurrence rates.

PMID- 20042151
TI  - Comparison of cephalometric norms of esthetically pleasing faces.
AB  - OBJECTIVE: To establish cephalometric norms of a sample of aesthetically pleasing
      Pakistani faces and to analyze differences and similarities with accepted
      standards for Caucasians. STUDY DESIGN: Analytical cross sectional study. PLACE
      AND DURATION OF STUDY: Carried out at Alvi Dental Hospital, Karachi, from August
      2007 to February 2008. METHODOLOGY: Cephalometric tracings were analyzed on a
      sample of 40 (20 males and 20 females) Pakistani young adults, aged 18-25 years,
      with full complement of permanent teeth, no previous orthodontic treatment and
      pleasing profile. To check the reliability of the measurements, 20 randomly
      selected cephalograms were retraced. None of the measurements showed a
      significant difference. Student's 't' test was applied for overall group
      comparisons. P-value of < 0.05 was considered significant. RESULTS: When compared
      with some classical standards, the results suggest that the Pakistani sample had
      greater cranial lengths (p < 0.001), shorter faces anteriorly (p < 0.001), and
      tended towards bimaxillary dental protrusion with more prominent chin (p <
      0.001). Males had greater antero-posterior, horizontal and vertical measurements
      (p < 0.001). Females showed more dental protrusion (p < 0.01). CONCLUSION:
      Comparisons revealed statistically significant differences in most variables
      between Pakistanis and Caucasians and between Pakistani males and females.
      Pakistanis have distinct cephalometric features, which should be used as a
      reference in treating Pakistani orthodontic and orthognathic surgery patients.

PMID- 20042152
TI  - Carotid artery disease in patients undergoing elective coronary artery bypass
      surgery.
AB  - OBJECTIVE: To determine frequency of carotid artery disease in patients
      undergoing elective coronary artery bypass grafting (CABG) using Doppler
      sonography. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY:
      Radiology Department, The Aga Khan University Hospital, Karachi, from January
      2005 to September 2008. METHODOLOGY: Patients with known cardiovascular disease
      waiting for CABG surgery were enrolled for carotid artery Doppler sonography. A
      predefined data entry form was used for data collection. Coronary angiography
      findings, carotid artery findings and other associated factors were noted from
      medical and radiological records. Frequency and pattern of carotid artery disease
      along with associated risk factors were evaluated. Data was entered and analyzed
      in SPSS version 15. Pearson chi-square for categorical and independent "t" test
      was applied for continuous variables at 95% confidence level. P-value of less
      than 0.05 were considered significant. RESULTS: A total of 176 patients (85%
      male, mean age=65 years) undergoing elective coronary artery bypass grafting were
      evaluated preoperatively for carotid artery disease by neck color Doppler
      sonography. Twenty percent of patients were found to have advanced carotid artery
      disease (> 50% stenosis), 6% had critical stenosis (> 75% stenosis) and 3% had
      complete stenosis. Frequency of atherosclerotic plaques was 50%, more common on
      right side and more prevalent in common carotid artery. Family background of
      carotid or coronary artery disease and history of smoking were significantly
      associated with presence of carotid artery disease (p < 0.05). CONCLUSION: A
      sizeable proportion of patients undergoing elective coronary artery bypass
      grafting surgery for coronary artery disease were found to have coexistant
      carotid artery disease.

PMID- 20042153
TI  - Open extraperitoneal mesh repair for abdominal wall hernias in females.
AB  - OBJECTIVE: To determine the outcome of treatment in terms of infection and
      recurrence using open extraperitoneal mesh repair technique. STUDY DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: The department of General
      Surgery, Combined Military Hospital, Bahawal Nagar Cantonment, from February 2006
      to November 2008. METHODOLOGY: Female patients with abdominal wall hernias with
      defect of 4 cm or more were studied. A history of previous surgery along with
      clinical findings on examination like size of defect and previous scar were
      noted. At surgery, hernial sacs were carefully opened and omental and intestinal
      adhesions were carefully separated. Polypropylene mesh was placed over
      extraperitoneal space and secured with interrupted vicryl 2/0 sutures. Redivac
      drains were placed over the mesh and the fascial repair. The patients were
      discharged on the 3rd - 4th postoperative day and were followed-up at 3 monthly
      intervals for postoperative sequelae like seroma, haematoma, infection and
      recurrence. RESULTS: There were 32 cases with a mean age of 41.25 + or - 10.79
      years. The mean follow-up period was 15.78 + or - 9.02 months. Previous abdominal
      surgical intervention was found in 16 (50%) cases. Out of those, 14 (43.7%) had
      defects through the previous scar. A history of multiple caesarean sections
      alone, or in combination with either hysterectomy or laparotomy in the last 5
      years was present in 7 patients. There were 12 (37.5%) cases of paraumbilical
      hernia, 4 (12.5%) of a recurrent paraumbilical hernia, 5 (15.6%) epigastric
      hernia, 2 (6.2%) mix hernia, 7 (21.8%) incisional hernia and 1 (3.1%) each of
      Spigelian hernia and postlaparoscopic cholecystectomy portal (paraumbilical)
      hernia. The mean size of the defect was 4.9 cm in primary paraumbilical hernias
      and 7.2 cm in recurrent paraumbilical hernias. The mean size of the defect in
      incisional hernias was 9.4 cm, larger than all other types. Superficial wound
      infection was seen in only 1 morbidly obese (BMI > 30) patient. No case of
      seroma, haematoma, deep seated abscess or recurrence was noted in the follow-up
      period. CONCLUSION: Abdominal wall hernias are common in female patients,
      especially those with previous surgical intervention. Open extraperitoneal mesh
      repair with placement of redivac drains is an effective method for the management
      of abdominal wall hernias with a smaller complication rate and less recurrence.

PMID- 20042154
TI  - Frequency of bone marrow involvement in Hodgkin's lymphoma on first presentation.
AB  - OBJECTIVE: To determine the frequency of bone marrow involvement in patients of
      Hodgkin's lymphoma on first presentation at oncology department. STUDY DESIGN:
      Case series. PLACE AND DURATION OF STUDY: The Oncology Department, Combined
      Military Hospital, Rawalpindi, from April 2006 to February 2007. METHODOLOGY:
      Thirty five patients of Hodgkin's lymphoma diagnosed on lymph node biopsy
      presenting for the first time at Oncology Department, Combined Military Hospital,
      Rawalpindi were included. They were admitted in the ward and evaluated with
      history, physical examination and staging investigations. Bone marrow trephine
      biopsy was performed in all patients. Descriptive statistics were used to analyze
      data. RESULTS: On clinical and radiological evaluation, 8 patients (22.9%) had
      clinical stage (CS), 12 (34.3%) had CS II, 9 (25.7%) had CS III and 6 (17.1%) had
      CS IV. The microscopic appearance in bone marrow trephine examination showed
      lymphoma infiltrates in 6 (17.14%) patients and chronic disorder in 29 (82.85%)
      patients. Among patients with bone marrow infiltration, one had CS II disease,
      three had CS III disease and two had CS IV disease. One patient had bone marrow
      infiltration as the only manifestation of disease. CONCLUSION: Bone marrow
      involvement was seen in patients with Hodgkin's lymphoma clinical stage II or
      higher.

PMID- 20042155
TI  - A clinicopathological study of urethritis in males.
AB  - OBJECTIVE: To determine the etiology and frequency of different types of
      urethritis in adult males. STUDY DESIGN: A case series. PLACE AND DURATION OF
      STUDY: The Dermatology Department of PNS Shifa Hospital, Karachi, from June 2004
      to December 2007. METHODOLOGY: One hundred male patients having complaints of
      urethral discharge and dysuria reporting in the skin OPD were included in the
      study. Patients who had received systemic treatment for their complaints and
      those who had other systemic infections were excluded. A detailed history
      including history of sexual contact was taken. Dermatological examination
      including examination of external genitalia was also performed. All these
      patients were subjected to complete physical examination, complete urine
      examination, urethral pus for gram staining and culture, endo-urethral swab with
      urethral loop for seeing Chlamydia antigen by fluorescent microscopy, cultures
      for ureaplasma and Wet mount specimen microscopy for trichomonas along with HIV
      (serum ELISA) test. Non-gonococcal urethritis was diagnosed on the presence of
      more than five polymorphonuclear leucocytes per high power field in at least five
      fields of Gram stained urethral smear, in the absence of Gram negative
      diplococci. RESULTS: The mean age was 29.2 + or - 5.8 years. Seventy (70%) cases
      were diagnosed as gonococcal urethritis and 30 (30%) cases as non-gonococcal
      urethritis (NGU). History of illicit sexual exposure was available in 25 (25%)
      patients. The interval period between initiation of symptoms and reporting of
      patient in gonococcal urethritis was 4 to 30 days (mean 12.8 days) and 4 days to
      2 months (mean 20.7 days) in non-gonococcal urethritis. The patients with
      gonococcal urethritis presented with purulent discharge in 66 (84%) cases, and
      dysuria in 49 (70%) cases. In the NGU group, 25 (80%) cases had mucoid discharge
      and 18 (65%) had dysuria. in 70%, Neisseria gonorrhoeae was isolated, Chlamydia
      trachomatis in 16%, ureaplasma in 8%, and Trichomonas vaginalis in 4%. No
      organism could be detected in 2% cases. HIV test was negative in all cases.
      CONCLUSION: Gonococcal urethritis was the commonest urethritis seen followed by
      Chlamydia infection in the studied group of adult males.

PMID- 20042156
TI  - Anemia and hypoalbuminemia at initiation of hemodialysis as risk factor for
      survival of dialysis patients.
AB  - OBJECTIVE: To determine the survival of patients undergoing chronic maintenance
      hemodialysis by determining the relative risk (RR) of anemia and hypoalbuminemia
      at initiation of dialysis on survival. STUDY DESIGN: Cohort study. PLACE AND
      DURATION OF STUDY: Hemodialysis Unit of Shalamar Hospital, Lahore, from June 2003
      to October 2006. METHODOLOGY: This study was conducted on all patients of end
      stage renal disease who presented in Accident/Emergency Department of the
      hospital for the first time or received calls from other departments in getting
      dialysis. Patients with acute renal failure and those lost to follow-up were
      excluded from the study. At presentation, a history and examination was done and
      recorded. At the same time a blood sample was sent for routine hematological
      parameters (hemoglobin, total leucocyte count (TLC), biochemical (urea,
      creatinine, serum potassium and albumin) and viral markers (anti-HCV and HbsAg).
      Patients were followed up for outcomes. The outcomes of the study were continued
      dialysis, death and renal transplant. Kaplan-Meier and log Rank tests were used
      for determining survival. Relative risk was assessed on medical 9.2. RESULTS: One
      hundred and eighty five patients were studied including 99 (52.8%) males and 86
      (47.2%) females. Major causes of renal failure were Diabetes mellitus in 125
      (67.6%), chronic glomerulonephrotis in 31 (16.8%) and hypertension in 18 (9.7%).
      Most of the patients - 105 (60%) were euvolemic. Sixty percent of patients had
      very high urea (> 200 mg/dl) and creatinine (> 8.0 mg/dl). The mortality of
      haemodialysis patients was seventy four percent per 100 patients per year, 62.24%
      being in the initial 6 months. One hundred and sixty four patients (91.1%) were
      anemic (hemoglobin < 11 gm/dl) and 124 (67%) were hypoalbuminemic (serum albumin
      < 4 gm/dl) on first presentation. Patients with group 1 have hemoglobin less than
      11 gm/dl (7.83 + or - 1.51), group 2 had hemoglobin of equal to more than 11
      gm/dl (11.56 + or - 0.64) which was statistically significant (t = - 9.54, p=
      0.000). The survival freedom in group 2 (Hb > 11 gm/dl) was higher than group 1
      (Hb < 11 gm/dl) which is statistical significant (p = 0.023). On the basis of
      serum albumin (S.Alb), patients were divided into two groups i.e S.Alb less than
      4 (3.15 + or - 0.38 gm/dl) was group 1, and more than or equal to 4 (4.23 + or -
      0.28 gm/dl) was group 2, which were statistically significant (t = - 11.58, p <
      0.001). The overall survival time was significantly shorter in group 1 patients
      than group 2 (p = 0.037). RR for low albumin was 1.27 and for low hemoglobin, it
      was 1.30. CONCLUSION: Mortality of haemodialysis patients was seventy four
      percent per 100 patients per year. Amongst these 62.24% were in the initial 6
      months. The mean survival time was 296 days. Patients with very low hemoglobin
      and albumin are at more risk for early deaths than patients with normal
      hemoglobin and albumin on first presentation for dialysis.

PMID- 20042157
TI  - Near-miss obstetrical events and maternal deaths.
AB  - OBJECTIVE: To determine the frequency of near-miss cases, nature of near-miss
      events and mortality among obstetric patients. STUDY DESIGN: Cross-sectional,
      observational study. PLACE AND DURATION OF STUDY: The study was conducted in the
      Obstetric Unit of Fatima Hospital, Baqai Medical University, from January 2006 to
      December 2006. METHODOLOGY: Near-miss case definition was based on validated
      specific criteria comprising of five diagnostic features: haemorrhage,
      hypertensive disorders in pregnancy, dystocia, infection and anemia. The main
      outcome measures were frequency and characteristics of near-miss cases, total
      hospital stay, high dependency unit/ICU stay and development of multiple organ
      dysfunction. Near-miss events and maternal deaths were described with respect to
      disease profiles. Mortality indices were determined for various disease processes
      to appreciate the standard of care provided for near-miss cases. The maternal
      death to near-miss ratio was calculated. RESULTS: There were 868 deliveries in
      the year 2006, 44 near-miss cases, 47 near-miss events and 6 maternal deaths. The
      maternal death to near-miss ratio was 1:7. The most common type of near-miss
      events were obstetrical haemorrhage, anemia and dystocia responsible for 51%,
      21.2% and 14.8% respectively. Severe hypertensive disorders in pregnancy and
      infections accounted for 8.5% and 4.2% of near-miss events. Postpartum
      haemorrhage was responsible for 83.3% and infection for 16.6% of the maternal
      deaths. The mortality index was higher for infections (33.3%) than for
      haemorrhage (17.2%). Organ system dysfunction/failure was diagnosed in 18.1% of
      near-miss cases. CONCLUSION: This study showed that for every 7 women who
      survived life threatening complications, one died. However, the underlying
      disease processes for near-miss and mortalities were almost same. Evaluation of
      the circumstances surrounding near miss cases could act as proxy for maternal
      deaths in the studied population.

PMID- 20042158
TI  - External Quality Assessment Scheme (IEQAS) in haematology at National Institute
      of Health, Islamabad, Pakistan.
AB  - OBJECTIVE: To document overall performance and improvement, if any, gained
      through participation in an International External Quality Assessment Scheme
      (IEQAS). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The
      Haematology Department, Public Health Laboratories Division, National Institute
      of Health, Islamabad, Pakistan, from January 1996 to December 2006. METHODOLOGY:
      Overall performance of blood parameters and parasite identification were
      analysed. Individual values were assessed against consensus value (mean + or -
      SD) and deviation index (DI) from the mean, whereas coefficients of variation
      (CV) were calculated for years 1996 to 2006. The results are expressed as
      percentage of accurate versus inaccurate results, deviation index (DI) and
      coefficient of variation (%CV). RESULTS: The laboratory achieved 87.74% of values
      within acceptable limits for haemoglobin, 72.03% for white blood count, 69.49%
      for platelet and 77.03% for reticulocyte estimation. Results were satisfactory,
      having DI values less than 3 for all four parameters. %CV values was found to be
      dependent on the type of test performed and varied among different parameters.
      Difficulty has been observed in identifying Plasmodium malariae and ovale.
      CONCLUSION: Participation in External Quality Assessment Schemes is extremely
      beneficial for the improvement of laboratory performance and quality of care.
      Evaluation of the survey results on a regular basis serves as a useful guide to
      assess overall performance of the laboratory. Standardization of analytical
      procedures, equipments and reagents, continuous monitoring of personnel
      competency and thorough investigation of discordant results significantly
      contributes to the delivery of quality diagnostic services.

PMID- 20042159
TI  - Primary percutaneous coronary aspiration of thrombus from infarct related artery.
AB  - We are reporting the case of a 48-year-old man hypertensive, and smoker
      presenting with acute inferoposterior ST elevation myocardial infarction (STEMI)
      with right ventricular infarction. He underwent diagnostic angiogram which
      revealed total occlusion of mid right coronary artery (RCA) by thrombus. Multiple
      runs of aspiration were performed using Export Aspiration Catheter-6F and
      thrombus was aspirated from RCA. Postaspiration stenting was deferred due to
      absence of any significant obstructive lesion. Some thrombus had migrated to
      distal right posteriolateral branch (RPLB). He was started on glycoprotein (GP)
      IIb IIIa inhibitors which had to stopped after a few hours due to upper
      gastrointestinal bleed. After 48 hours a re-look angiogram demonstrated good flow
      in RCA with resolution of the residual thrombus.

PMID- 20042160
TI  - Brucella melitensis presenting as erythema nodosum-like lesions.
AB  - Brucellosis is a chronic granulomatous zoonosis with protean manifestations.
      Cutaneous involvement in Brucellosis is a relatively rare phenomenon. We describe
      a case of Brucella melitensis infection presenting with erythema nodosum like
      skin lesions involving palms and soles in a 70 years old lady.

PMID- 20042161
TI  - Vitiligo appearing in striae distensae as a Koebner phenomenon.
AB  - Koebner phenomenon, the appearance of preexisting skin lesions following trauma
      to previously uninvolved skin, has been seen frequently with vitiligo. The type
      of trauma leading to Koebner phenomenon can vary from scratching, surgical scars,
      radiotherapy, burns, irritation from drug use and laser therapy. Striae distensae
      are a form of injury to the skin and in this particular case resulted from rapid
      increase in body size at puberty and possibly the use of systemic steroids for
      the treatment of vitiligo. The appearance of vitiligo in striae distensae as a
      form of Koebner phenomenon has been reported rarely. We describe a 14-year-old
      boy with vitiligo for the past 2 years, which Koebnerized in the striae
      distensae.

PMID- 20042162
TI  - Acute parapharyngeal abscess secondary to streptococcal mastoiditis.
AB  - A rare case of parapharyngeal abscess caused by Streptococcus pneumoniae
      presenting as neck abscess is reported. The patient had 20 days history of cough,
      fever and swelling behind right ear. He had not responded to multiple antibiotic
      treatments given earlier. On the basis of clinical examination and CT scan
      finding, he was diagnosed as having parapharyngeal abscess pointing in the neck.
      The abscess was drained and the patient was treated with injectable Ceftriaxone,
      due to identification of penicillin - resistant Streptococcus pneumoniae.

PMID- 20042163
TI  - Non-traumatic right hepatic artery pseudoaneurysm: an unusual cause of hemobilia
      and obstructive jaundice.
AB  - Most hepatic artery pseudoaneurysms (HAPA) are post traumatic, and non-traumatic
      pseudoaneurysm is rarely reported. It is a potentially life threatening vascular
      disorder and difficult to diagnose before rupture. Early diagnosis and prompt
      nonoperative intervention of this lesion could be life saving. The authors report
      the case of a patient with hemobilia caused by ruptured right hepatic artery
      pseudoaneurysm and subsequently developed right hepatic duct stricture, which has
      not been reported previously. This patient was successfully treated with
      endovascular stent graft of pseudoaneurysm and endoscopic stenting of right
      hepatic duct stricture.

PMID- 20042164
TI  - Disproportionate short stature with multisystem involvement - Ellis-van Creveld
      syndrome.
AB  - Ellis-van Creveld syndrome is a rare form of mesenchymal - ectodermal dysplasia.
      It is an autosomal recessive disorder characterized by disproportionate short
      stature, postaxial polydactyly, ectodermal dysplasia and congenital heart defect.
      This case report presents two cases with classical clinical findings along with
      some unusual features including rhizomelic limb shortening, global developmental
      delay and bilateral lens subluxation not reported previously.

PMID- 20042165
TI  - Molecular confirmation of the causes of inherited visual impairment in Northern
      Pakistan.
AB  - Families with inherited visual impairment were identified and examined from
      January 2000 to December 2005 and given a clinical diagnosis. Known genes and
      loci were screened for mutations or linkage at Institute of Ophthalmology and
      Neurosciences, University of Leeds, in order to provide molecular confirmation.
      Inherited retinal disease was the most common cause of inherited visual
      impairment in 38 of 57 families (66.6%) with Leber's congenital amaurosis, rod
      cone dystrophy and cone-rod dystrophy being the most common diagnoses in 22, 8
      and 3 families respectively. Anterior segment dysgenesis was diagnosed in 8
      families (14%). Mutations in known genes or linkage to known loci were identified
      in 23 of 57 families (40%). All families had molecular confirmation of autosomal
      recessive inheritance or a pedigree consistent with this mode of inheritance,
      with evidence of first-cousin marriage. Knowledge of carrier status and genetic
      counseling may allow families to make an informed decision regarding marriage,
      and thus begin to plan a way of reducing the incidence of inherited visual
      impairment.

PMID- 20042169
TI  - The incidence of urinary incontinence across Asian, black, and white women in the
      United States.
AB  - OBJECTIVE: We calculated incidence rates of urinary incontinence by incontinence
      frequency and type over 4 years in Asian, black, and white women in the United
      States. STUDY DESIGN: Prospective analyses included 76,724 participants aged 37
      79 years in the Nurses' Health Study cohorts with no incontinence at baseline.
      RESULTS: The 4-year incidence of incontinence at least monthly was higher in
      white women (7.3/100 person-years) compared with Asian (5.7/100 person-years; P =
      .003) and black women (4.8/100 person-years; P < .001). The incidence of at least
      weekly stress incontinence was significantly lower in black compared with white
      women (0.1 vs 0.8 per 100 person-years; P < .001). The difference between black
      and white women in the incidence of any incontinence and stress incontinence
      remained significant after adjusting for known risk factors (P < .001 for both).
      CONCLUSION: Urinary incontinence incidence differs by race. Studies to confirm
      these results and better understand underlying mechanisms are needed.

PMID- 20042170
TI  - Vitamin D "advertisement".

PMID- 20042173
TI  - Experiences in abdominal radical trachelectomy.

PMID- 20042174
TI  - Laparoscopy vs vaginal hysterectomy with culdolaparoscopy oophorectomy.

PMID- 20042175
TI  - Alternatives to management of cervical prolapse in labor.

PMID- 20042176
TI  - Impact of labor at prior cesarean on lower uterine segment thickness in
      subsequent pregnancy.
AB  - OBJECTIVE: The objective of the study was to identify the factors associated with
      sonographic lower uterine segment (LUS) thickness near term in women with prior
      low transverse cesarean. STUDY DESIGN: A prospective cohort study of women with a
      single prior low transverse cesarean was conducted. LUS thickness was quantified
      by transabdominal ultrasound with repeated transvaginal measurement when
      necessary. The thinnest measurement was considered as the dependent variable.
      Potential related factors were evaluated with nonparametric analyses and
      multivariate logistic regressions. RESULTS: Two hundred thirty-five women were
      recruited at a mean gestational age of 36.7 +/- 1.3 weeks. The full LUS was
      thicker in women who had their previous cesarean during the latent phase (2.8 mm;
      interquartile [IQ], 2.0-3.3 mm) or the active phase of labor (3.1 mm; IQ 2.5-3.9
      mm) than in women with previous cesarean prior to labor (2.4 mm; IQ 2.0-3.2 mm).
      The association remained significant after adjustment for potential confounders.
      CONCLUSION: Presence of labor at previous cesarean is associated with a thicker
      LUS in a subsequent pregnancy.

PMID- 20042177
TI  - Protective effect of paraoxonase 1 gene variant Gln192Arg in age-related macular
      degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness
      among older adults, in which oxidative damage may play a pivotal role.
      Paraoxonase 1 (PON1) protects against oxidative damage and has been evaluated for
      its involvement in aging diseases including AMD. This study investigated whether
      PON1 gene polymorphisms associate with AMD. DESIGN: Case-control association
      study. METHODS: We studied 1037 individuals with AMD subcategorized using AREDS
      criteria and 370 control subjects without retinal disease. Participants were
      primarily Caucasian of European descent. All exons of PON1 were evaluated by
      single-strand conformation polymorphism and direct sequence analysis. RESULTS:
      Six missense changes (Leu55Met, Met127Arg, His155Arg, Gln192Arg, Gln192Glu,
      Ala252Gly) were identified in PON1. We observed a weak association of Leu55Met
      with an increased risk of wet AMD (P = .02), but not with dry AMD or when
      combining all patient categories. A significantly higher allele frequency for
      Gln192Arg was detected in controls than in the combined AMD patient population (P
      < .0001), and when category 2, 3, and 4 patients were separately considered (P =
      .004, P = .002, and P < .0001, respectively). For category 4 AMD, the Arg192
      allele was significantly less prevalent in the wet form (P < .0001), but not in
      the dry form (P = .377). CONCLUSION: We report a weak association of PON1
      Leu55Met with an increased risk of wet AMD, replicating previous reports. Our
      findings indicate a protective role for Gln192Arg, particularly for patients with
      the wet form. Gln192Glu warrants consideration, as this variant alters the same
      amino acid as Gln192Arg and was identified only in category 4 AMD patients. We
      believe that Met127Arg, His155Arg, and Ala252Gly play minor roles in AMD
      susceptibility because of their limited frequency and/or location within the PON1
      gene. The functional and biological mechanism by which Gln192Arg is acting to
      decrease AMD susceptibility remains to be determined.

PMID- 20042178
TI  - Mycophenolate mofetil for ocular inflammation.
AB  - PURPOSE: To evaluate mycophenolate mofetil as a single noncorticosteroid
      immunosuppressive treatment for noninfectious ocular inflammatory diseases.
      DESIGN: Retrospective cohort study. METHODS: Characteristics of patients with
      noninfectious ocular inflammation treated with mycophenolate mofetil at 4
      subspecialty clinics from 1995 to 2007 were abstracted by expert reviewers in a
      standardized chart review of every eye at every visit. Main outcomes measured
      were control of inflammation, corticosteroid-sparing effects, and discontinuation
      of mycophenolate mofetil (including the reasons for discontinuation). Survival
      analysis was used to estimate the incidence of outcomes, and to identify risk
      factors for each. RESULTS: Among 236 patients (397 eyes) treated with
      mycophenolate mofetil monotherapy, 20.3%, 11.9%, and 39.8% had anterior uveitis,
      intermediate uveitis, and posterior uveitis or panuveitis respectively; 14% had
      scleritis; 7.6% had mucous membrane pemphigoid; and 6.4% had other ocular
      inflammatory diseases. By Kaplan-Meier estimation, complete control of
      inflammation--sustained over consecutive visits spanning at least 28 days--was
      achieved in 53% and 73% of patients within 6 months and 1 year respectively.
      Systemic corticosteroid dosage was reduced to 10 mg of prednisone or less, while
      maintaining sustained control of inflammation, in 41% and 55% of patients in 6
      months and 1 year respectively. Twelve percent of patients discontinued
      mycophenolate mofetil within the first year because of side effects of therapy.
      CONCLUSIONS: Given sufficient time, mycophenolate mofetil was effective in
      managing ocular inflammation in approximately half of the treated patients.
      Treatment-limiting side effects were observed in 12% of patients and typically
      were reversible.

PMID- 20042179
TI  - Retinal thickness analysis by race, gender, and age using Stratus OCT.
AB  - PURPOSE: To detect differences in retinal thickness among patients of different
      race, gender, and age using Stratus OCT. DESIGN: Cross-sectional study. METHODS:
      In a multicenter, university-based study, 126 patients with no history of ocular
      disease were enrolled (78 diabetics without retinopathy and 48 nondiabetics).
      Optical coherence tomography measurements were performed using Stratus OCT.
      Statistical comparisons of center point foveal thickness and mean foveal
      thickness were made using generalized estimating equations adjusting for diabetic
      status, race, age, and gender. RESULTS: The study population consisted of 36%
      male subjects, 39% Caucasian, 33% African-American, and 28% Hispanic. Mean foveal
      thickness was 191.6 +/- 2.7 microm and 194.5 +/- 2.7 microm for diabetics and
      nondiabetics, respectively (P = .49). Mean foveal thickness in male subjects was
      significantly larger than in female (201.8 +/- 2.7 microm and 186.9 +/- 2.6
      microm, respectively; P < .001). Mean foveal thickness was 200.2 +/- 2.7 microm
      for Caucasian, 181.0 +/- 3.7 microm for African-American, and 194.7 +/- 3.9
      microm for Hispanic subjects. Mean foveal thickness was significantly less for
      African-American than Caucasian (P < .0001) or Hispanic subjects (P = .005).
      Center point foveal thickness and mean foveal thickness showed a significant
      increase with age. CONCLUSIONS: There are statistically significant differences
      in retinal thickness between subjects of different race, gender, and age. When
      compared to Caucasian and Hispanic subjects, African-American race is a predictor
      of decreased mean foveal thickness; and male sex (regardless of race) is a
      significant predictor of increased mean foveal thickness. Mean foveal thickness
      is similar among diabetics and nondiabetics when data are controlled for age,
      race, and sex. These results suggest that studies comparing OCT measurements
      should carefully control for age-based, race-based, and gender-based variations
      in retinal thickness.

PMID- 20042181
TI  - Paretic side/normal side ratios of cross-sectional areas of the superior oblique
      muscle vary largely in idiopathic superior oblique palsy.
AB  - PURPOSE: To search for a new definition of muscle hypoplasia in congenital or
      idiopathic superior oblique muscle palsy. DESIGN: Retrospective case-control
      study. METHODS: Cross-sectional areas of the superior oblique and 4 rectus
      muscles near the eye globe-optic nerve junction were measured by an image
      analysis software on magnetic resonance images of 50 patients with congenital or
      idiopathic superior oblique muscle palsy and 45 patients with other disease
      conditions serving as a control. The paretic side/contralateral normal side
      ratios of the cross-sectional areas and the left side/right side ratios were
      calculated for the superior oblique muscle palsy patients and the control
      patients, respectively. RESULTS: The 95% confidence intervals in paretic
      side/contralateral side ratios of cross-sectional areas of the superior oblique
      muscle were 0.55 to 0.80 in the right-side superior oblique muscle palsy, and
      0.48 to 0.75 in the left-side palsy, while the 95% confidence interval in the
      left side/right side ratios was 0.99 to 1.00 in the control. The 95% confidence
      intervals in the left side/right side ratios of the 4 rectus muscles were 1.00,
      both in the superior oblique muscle palsy and in the control. CONCLUSIONS: The
      muscle hypoplasia could be defined as such when the paretic side/contralateral
      side ratios of cross-sectional areas of the superior oblique muscle on magnetic
      resonance images fell outside the 95% confidence interval of the ratios in normal
      controls.

PMID- 20042180
TI  - One-year results of reduced-fluence photodynamic therapy for polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To report 1-year results of reduced-fluence photodynamic therapy (PDT)
      for polypoidal choroidal vasculopathy (PCV) in Japanese patients. DESIGN:
      Prospective interventional case series. METHODS: In the present study, 28
      treatment-naive eyes of 28 consecutive patients underwent PDT with a reduced
      laser fluence of 25 J/cm(2). Patients were followed up at baseline and 1 week and
      3, 6, 9, and 12 months after PDT. Choroidal perfusion changes were evaluated by
      indocyanine green angiography (ICGA) and leakage from PCV lesions and exudative
      changes by fluorescein angiography and optical coherence tomography. Treatment
      safety was assessed according to visual acuity (VA) and adverse events. The best
      corrected VA (BCVA) obtained by Landolt ring tests was converted into the
      logarithm of the minimal angle of resolution (logMAR). RESULTS: At baseline, the
      mean logMAR BCVA was 0.45 (geometric mean: 7/20). At 12 months, the mean logMAR
      BCVA significantly improved to 0.29 (geometric mean: 10/20) (P = 0.0001). The
      logMAR BCVA was stable or improved by >or=0.2 in 26 eyes (93%) at 1-year follow
      up. In 10 eyes with VA better than 20/40 at baseline, the mean logMAR BCVA was
      significantly improved compared with baseline at 12 months. Although 16 of 28
      eyes (57%) showed mild to moderate nonperfusion of choriocapillaris in early ICGA
      at 1 week, 27 eyes (96%) showed recovery to pretreatment levels at 3 months. Mean
      number of treatment sessions during the 12 months was 1.3. No severe side effects
      related to treatment were encountered. CONCLUSIONS: Reduced-fluence PDT is an
      effective treatment for PCV and could improve vision even in eyes with VA better
      than 20/40.

PMID- 20042182
TI  - The effect of internal and external fields of view on visually induced motion
      sickness.
AB  - Field of view (FOV) is said to affect visually induced motion sickness. FOV,
      however, is characterized by an internal setting used by the graphics generator
      (iFOV) and an external factor determined by screen size and viewing distance
      (eFOV). We hypothesized that especially the incongruence between iFOV and eFOV
      would lead to sickness. To that end we used a computer game environment with
      different iFOV and eFOV settings, and found the opposite effect. We speculate
      that the relative large differences between iFOV and eFOV used in this experiment
      caused the discrepancy, as may be explained by assuming an observer model
      controlling body motion.

PMID- 20042183
TI  - Suppression of murine experimental autoimmune encephalomyelitis by interleukin-2
      receptor targeted fusion toxin, DAB(389)IL-2.
AB  - Previously we have shown that DAB(389)IL-2, a recombinant fusion toxin targeting
      IL-2R bearing cells, suppressed disease in the rat experimental autoimmune
      encephalomyelitis (EAE) model of acute multiple sclerosis (MS). Our present study
      demonstrates that DAB(389)IL-2 can also effectively suppress acute (A)-EAE,
      relapsing (R)-EAE and chronic (C)-EAE in mouse demyelinating models. DAB(389)IL-2
      significantly suppressed mitogenic proliferation of spleen cells while mutant
      fusion proteins DA(glu53)B(389)IL-2 and DAB(389)IL-2(8-10) did not. EAE was
      successfully suppressed when DAB(389)IL-2 was administered in various regimens
      between days 1 and 15 post immunization in all three models. CD4(+)IL-2R(+) cells
      were reduced in the spleen but not in the lymph nodes of DAB(389)IL-2-treated
      mice during A-EAE while the number of CD8(+) cells was unchanged. DAB(389)IL-2
      also significantly reduced the number of CD4(+), CD8(+), CD25(+),
      TCRgammadelta(+) phenotype and CD11b(+) macrophages/microglia within spinal cord
      lesions. These data strongly suggest that DAB(389)IL-2 specifically targeted
      myelin protein-activated CD4(+) T cells and strengthens the argument for the use
      of DAB(389)IL-2 in treatment strategies for MS.

PMID- 20042184
TI  - Creating number semantics through finger movement perception.
AB  - Communication, language and conceptual knowledge related to concrete objects may
      rely on the sensory-motor systems from which they emerge. How abstract concepts
      can emerge from these systems is however still unknown. Here we report a
      functional interaction between a specific meaningful finger movement, such as a
      finger grip closing, and a concept as abstract as numerical magnitude.
      Participants were presented with Arabic digits to recall before or after they
      perceived a biological or non-biological hand movement. The results show that
      perceiving a grip closing slows down the processing of large magnitude numbers.
      Importantly, we show that this motor-to-semantic interaction differs from the
      reverse semantic-to-motor interaction, and that it does not result from a general
      movement amplitude processing as it is only observed for biological hand
      movements. These results demonstrate the functional link between number meaning
      and goal-directed finger movements, and show how abstract concept semantics can
      emerge from the sensory-motor circuits of the brain.

PMID- 20042185
TI  - GaitaBase: Web-based repository system for gait analysis.
AB  - The need to share gait analysis data to improve clinical decision support has
      been recognised since the early 1990s. GaitaBase has been established to provide
      a web-accessible repository system of gait analysis data to improve the sharing
      of data across local and international clinical and research community. It is
      used by several clinical and research groups across the world providing cross
      group access permissions to retrieve and analyse the data. The system is useful
      for bench-marking and quality assurance, clinical consultation, and collaborative
      research. It has the capacity to increase the population sample size and improve
      the quality of 'normative' gait data. In addition the accumulated stored data may
      facilitate clinicians in comparing their own gait data with others, and give a
      valuable insight into how effective specific interventions have been for others.

PMID- 20042186
TI  - A novel indexing architecture for the provision of smart playback functions in
      collaborative telemedicine applications.
AB  - This paper presents a novel indexing architecture to support a range of smart
      playback functions in collaborative telemedicine systems. These functions include
      replaying the session from a specified point in time, replaying all the session
      segments controlled by a particular physician, replaying all the session segments
      relating to a specific medical image, and playing a montage of the entire
      session. Since the contents of telemedicine sessions vary over time depending on
      the particular commands invoked by the physician(s) during the session, when
      executing the smart playback functions, it is necessary to restore the target
      image contents to the appropriate condition before commencing the playback
      routine. In this study, this is achieved by using an indexing scheme designated
      as three-level indexing hierarchy (TIH) to search for the appropriate cut-in
      point in the session and to identify the commands which should be applied to
      restore the current image contents to their original condition at the cut-in
      point. In the proposed indexing scheme, the performance of the cut-in point
      determination process and the content restoration procedure is enhanced by
      maintaining a link between all the changes which take place in the image contents
      over the duration of the session and the commands which induce these changes. The
      evaluation results confirm that TIH outperforms existing scene-based retrieval
      systems in terms of both an improved computational efficiency and a lower storage
      requirement.

PMID- 20042187
TI  - Morbid obesity: pregnancy risks, birth risks and status of the newborn.
AB  - In perinatal medicine, severe obesity of the mother occurs in approximately 1% of
      cases. This is a problem of increasing importance because of the rising
      prevalence of juvenile obesity. Our retrospective cohort study aimed at
      characterising high-risk pregnancies associated with morbid obesity (body mass
      index [BMI]> or =40). This is of interest not only from an epidemiological
      perspective and for developing guidelines for clinical care but also from an
      anthropological point of view. We analysed the German perinatal statistics of the
      years 1998-2000 with data from more than 500,000 pregnancies. Pregnant women with
      coexistent morbid obesity were compared to a normal weight reference sample with
      regard to gestational, perinatal and neonatal risks. Birth weight percentiles
      were used to classify the neonates according to size (hypotrophy if <10th,
      hypertrophy/foetal macrosomia if >90th). The obtained risk profile for morbidly
      obese pregnant women primarily showed pregnancy related diseases, such as
      hypertension, pre-eclampsia and gestational diabetes. Hypertension and signs of
      foetal hypoxaemia occurred at higher frequencies with morbid obesity.
      Hypertrophic neonates were born 3.3 times more often to obese mothers than to
      mothers of the normal weight. At a BMI> or =40 the rates of complications such as
      pre-eclampsia, gestational diabetes, impending foetal hypoxaemia, foetal
      macrosomia, as well as neonatal infections and hyperbilirubinaemia were
      significantly higher. Obesity and maternal comorbidities, accounted for a higher
      rate of caesarean sections of up to 38.4% at a BMI> or =45. All differences were
      highly significant. Preconceptionally, the therapeutic approach should be weight
      reduction.

PMID- 20042188
TI  - Japanese single women have limited knowledge of age-related reproductive time
      limits.

PMID- 20042189
TI  - The genetics of statin-induced myopathy.
AB  - OBJECTIVE: Our goal was to use genetic variants to identify factors contributing
      to the muscular side effects of statins. BACKGROUND: Statins (3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors) are usually well tolerated
      medications, but muscle symptoms, ranging from mild myalgia to clinically
      important rhabdomyolysis are an important side effect of these drugs and a
      leading cause of noncompliance. Recent results suggest that genetic factors
      increase the risk of statin-related muscle complaints. We performed a systematic
      review of the medical literature to determine genetic factors associated with
      statin myopathy. METHODS: We identified English language articles relating statin
      myopathy and genetic diseases and gene variants via a PubMed search. Articles
      pertinent to the topic were reviewed in detail. RESULTS/CONCLUSIONS: Our review
      suggests that some patients are susceptible to statin myopathy because of pre
      existing subclinical inherited muscular disorders, or genetic variation in statin
      uptake proteins encoded by SLCO1B1 or the cytochrome P enzyme system. Variations
      in genes affecting pain perception and polymorphism in vascular receptors may
      also contribute to statin myopathy. None of the variants identified in this
      review suggested novel metabolic mechanisms leading to statin myopathy.

PMID- 20042190
TI  - Increased macrophage cholesterol biosynthesis and decreased cellular paraoxonase
      2 (PON2) expression in Delta6-desaturase knockout (6-DS KO) mice: beneficial
      effects of arachidonic acid.
AB  - OBJECTIVE: To analyze the possible role of arachidonic acid (AA) in macrophage
      cholesterol biosynthesis and in PON2 expression. METHODS AND RESULTS: We used
      peritoneal macrophages (MPM) from the 6-DS KO mice that were fed a diet without
      or with AA. Macrophage cholesterol biosynthesis rate and HMGCoA-reductase mRNA
      levels were substantially increased, by 98% and 67%, respectively, in MPM from 6
      DS KO vs. control (C57BL/6) mice. Furthermore, in the 6-DS KO vs. control mice
      MPM PON2 expression (mRNA and lactonase activity) was substantially decreased. In
      line with the above results, AA supplementation to 6-DS KO mice significantly
      decreased MPM cholesterol biosynthesis rate and HMGCoA-reductase mRNA levels, by
      45% and by 4-fold respectively, and increased MPM PON2 lactonase activity and
      PON2 mRNA, by 119% and 2.3-fold, respectively. Similarly, incubation of control
      mice MPM or J774A.1 with AA, significantly and dose-dependently decreased
      cellular cholesterol biosynthesis rate, and increased PON2 expression. These
      effects were specific for AA since incubation of the cells with docosahexaenoic
      acid (DHA, another product of 6-DS) had no significant effects on cholesterol
      biosynthesis rate, and on PON2 activity. CONCLUSIONS: AA decreased macrophage
      cholesterol biosynthesis rate, and increased PON2 expression. These effects could
      protect the cells from cholesterol accumulation and oxidation, and from foam cell
      formation, the hallmark of early atherogenesis.

PMID- 20042192
TI  - Fluorous media for extraction and transport.
AB  - Selective partitioning can be useful for sample cleanup or the isolation and
      purification of desired compounds. Fluorocarbon solvents and polymers, and
      solvents or polymers with similar properties that are not composed solely of
      carbon and fluorine (so-called 'fluorous' solvents or polymers) have a low
      ability to dissolve or sorb solutes or penetrants. This lack of solvating ability
      can lead to selective extractions. Fluorous phases will solvate, and therefore
      extract or transport, fluorous solutes, or non-fluorous solutes that are
      stabilized in the fluorous phase by non-covalent interactions with a 'host' or
      'receptor' molecule that is in the fluorous phase. In this review, there is a
      brief discussion of molecular recognition as applied to selective extraction.
      Fluorous solvents are introduced, and there is a description of some recent
      applications, chiefly in synthetic organic chemistry. In particular, it is
      important to understand solute partitioning behavior and methods to predict it
      when one of the solvents is fluorous. Fluorous polymers Teflon AF1600 and AF2400
      have been used in separations. Their rather complex and still not completely
      understood properties in separations and transport are described. There is a
      discussion of molecular recognition in fluorous phases as well as a brief
      discussion of efficient methods of carrying out extractions for analytical or
      physicochemical purposes.

PMID- 20042191
TI  - Altering dietary lysine:arginine ratio has little effect on cardiovascular risk
      factors and vascular reactivity in moderately hypercholesterolemic adults.
AB  - BACKGROUND: Information is scarce regarding the effect of dietary protein type,
      with specific focus on the lysine-to-arginine (Lys:Arg) ratio, on cardiovascular
      risk factors and vascular reactivity in humans. OBJECTIVE: Determine the effect
      of dietary Lys:Arg ratio on cardiovascular risk factors and vascular reactivity
      in moderately hypercholesterolemic adults. DESIGN: Randomized cross-over design
      of two 35-day diet phases; thirty adults (21 females and 9 males, >or=50 years,
      LDL cholesterol>or=120 mg/dL). Diets had 20% energy (E) protein, 30%E fat, 50%E
      carbohydrate and were designed to have low (0.7) or high (1.4) Lys:Arg ratio.
      Measures included fasting and postprandial lipid, lipoprotein, apolipoprotein
      concentrations; fasting high sensitivity C-reactive protein (hsCRP), small dense
      LDL (sdLDL) cholesterol, remnant lipoprotein cholesterol (RemLC), glycated
      albumin, adiponectin and immunoreactive insulin concentrations, endogenous
      cholesteryl ester transfer protein (CETP) and lecithin:cholesterol acyl
      transferase (LCAT) activities; cholesterol fractional synthesis rate (FSR); and
      flow mediated dilation (FMD) and peripheral artery tonometry (PAT). RESULTS: No
      differences were observed in fasting and/or postprandial total, LDL, HDL and
      sdLDL cholesterol, RemLC, Lp(a) or apo B concentrations, LCAT and CETP
      activities, FSR, glycated albumin, immunoreactive insulin, FMD or PAT. The low,
      relative to the high, Lys:Arg ratio diet resulted in lower postprandial VLDL
      cholesterol (-24%, P=0.001) and triglycerides (-23%, P=0.001), and small but
      significant differences in fasting (-3%, P=0.003) and postprandial (-3%, P=0.018)
      apo AI, and fasting adiponectin concentrations (+7%, P=0.035). Fasting and
      postprandial hsCRP concentrations were 23% lower after the low Lys:Arg ratio diet
      (P=0.020 for both). CONCLUSIONS: Diets differing in Lys:Arg ratios had no or
      small effects on cardiovascular risk factors and vascular reactivity.

PMID- 20042193
TI  - Influence of surfactant structure on the contribution of micelles to Ostwald
      ripening in oil-in-water emulsions.
AB  - The rate of Ostwald ripening was measured, using light scattering, in 2 wt.% and
      10 wt.% decane-in-water and dodecane-in-water emulsions. Sodium dodecyl sulfate
      and several nonionic ethylene oxide dodecyl ethers--surfactants with tails
      containing 12 carbons, but with various headgroups--were used to form the
      emulsions. Emulsions were formed with sufficient quantities of the surfactant to
      saturate the droplet interfaces. The influence of surfactant micelles in the
      continuous phase was then explored by adding 1-5 wt.% surfactant to the water.
      The increase in the average droplet radius in the absence of micelles was found
      to agree qualitatively with Lifshitz-Slyozov-Wagner theory for the different
      surfactant types. The addition of micelles increased the rate of Ostwald
      ripening, by factors between 2 and 50, depending on the type and concentration of
      surfactant. However, there was no systematic correspondence between the increased
      rate and the equilibrium solubilization capacity of the micelles, nor was the
      rate decreased with increased strength of repulsive interactions between micelle
      and the droplet interface. It is proposed that the complex influence of
      surfactant on Ostwald ripening kinetics may depend on the ability of micelles to
      become supersaturated with oil--i.e., to incorporate solute temporarily above
      their equilibrium solubilization capacity.

PMID- 20042194
TI  - Temperature effects on the hydrophobic interaction of parallel plates in the
      framework of the probabilistic approach to hydrogen bonding.
AB  - Recently, we have proposed a probabilistic approach to examine the effect of
      water-water hydrogen bond networks around two foreign hydrophobic particles
      (immersed in water) on their interaction. Because of the proximity to a particle,
      a water molecule in the first hydration shell around it forms a smaller number of
      hydrogen bonds compared to a bulk molecule. The probabilistic approach allows one
      to analytically evaluate the former number if the latter is known (which is
      usually the case). On the other hand, the former bonds may be slightly
      (energetically) enhanced compared to the latter if at least one of the two bonded
      molecules lie in the first hydration shell and does not form a bond with a
      nearest neighbor site on the particle surface. When two hydrophobic particles are
      sufficiently close to each other, the overlap of boundary water-water hydrogen
      bond networks gives rise to an additional attractive force between them. In this
      paper we use the probabilistic approach to examine the effect of solvent
      temperature on the solvent-mediated interaction of two hydrophobic particles.
      Their hydrophobic attraction is affected by the solvent (water) temperature
      because the density of the solvent, strength of a hydrogen bonds, and number of
      hydrogen bonds per molecule are sensitive thereto (the pressure effects are not
      considered here). The probabilistic approach predicts that the solvent-mediated
      attraction of hydrophobic solutes is driven by the favorable entropic component
      ("-temperature x entropy") of the potential of mean force that dominates the
      unfavorable energetic component. This attraction decreases as the temperature
      increases.

PMID- 20042195
TI  - Identification of equine cutaneous lymphangioma by application of a lymphatic
      endothelial cell marker.
AB  - An adult horse was presented with a mass located within the dermis and subcutis
      of the right forelimb. At post-mortem examination there was a marked increase in
      thickness of the subcutis of the right forelimb extending from the fetlock to the
      pectoral muscles. Microscopically, the dermis and subcutis were diffusely
      infiltrated by endothelial-like cells forming irregular channels and cavernous
      spaces. Immunohistochemical examination revealed the endothelial-like cells to
      express vimentin, factor VIII-related antigen and PROX-1, confirming the identity
      of the tumour as a lymphangioma. Ultrastructural analysis showed that the
      cavernous spaces were lined by a discontinuous endothelium lacking any basement
      membrane.

PMID- 20042196
TI  - Long-term cognitive dynamics of fluent reading development.
AB  - Most theories of reading development assume a shift from slow sequential subword
      decoding to automatic processing of orthographic word forms. We hypothesized that
      this shift should be reflected in a concomitant shift in reading-related
      cognitive functions. The current study investigated the cognitive dynamics
      underlying reading development in a large school sample ranging from beginning to
      experienced readers. The results showed that phonological awareness (PA) and
      rapid automatized naming (RAN) contributed substantially to reading fluency over
      all six primary school grades. However, the relationship between PA and word (but
      not pseudoword) reading fluency decreased as a function of reading experience,
      whereas the relationship between RAN and word reading fluency increased
      gradually. Moreover, this cognitive shift was most pronounced for high-frequency
      words. The results seem to point to the development of one (and only one) reading
      network for all types of words in which processing load or type of processing
      depends on word familiarity and amount of reading experience.

PMID- 20042197
TI  - Spinocerebellar variant of adrenoleukodystrophy with a novel ABCD1 gene mutation.
AB  - X-linked adrenoleukodystrophy (X-ALD) shows a wide range of phenotypic
      expression, and clinical presentation as adult-onset spinocerebellar ataxia has
      been rarely reported. Here, we report a Taiwanese family with X-ALD. The proband,
      a 37-year-old man presented with dysarthria, cerebellar ataxia and mild spastic
      paraparesis, and had atrophy of cerebellum and upper cervical cord on MRI. One of
      his nephews, a 9-year-old boy had a classic childhood cerebral ALD phenotype.
      This family harbors a novel deletion of 1 base pair in exon 8 at nucleotide
      position 2245 (2245delA) in the ABCD1 gene. This is the first report of the
      2245delA mutation presenting with a spinocerebellar variant of X-ALD.

PMID- 20042198
TI  - Sisters with clinically mild encephalopathy with a reversible splenial lesion
      (MERS)-like features; Familial MERS?
AB  - We first report sisters presenting with clinically mild
      encephalitis/encephalopathy with a reversible splenial lesion (MERS)-like
      features, i.e., mild and reversible neurological manifestations, and MRI finding
      of a reversible lesion with transiently reduced diffusion in the corpus callosum
      associated with symmetrical white matter. The distributions of the white matter
      lesions (more extensive) and Na levels (normal) were different from those
      reported for sporadic MERS patients (subcortical white matter close to the
      central sulci, and hyponatremia), which suggested that the pathophysiology of the
      sisters with MERS-like features might be different from that of sporadic MERS.
      Some genetic factors might be involved in MERS, especially in some patients with
      extensive white matter lesions.

PMID- 20042200
TI  - Nonoperative thoracic duct embolization for traumatic thoracic duct leak:
      experience in 109 patients.
AB  - OBJECTIVE: To demonstrate the efficacy of a minimally invasive, nonoperative,
      catheter-based approach to the treatment of traumatic chyle leak. METHODS: A
      retrospective review of 109 patients was conducted to assess the efficacy of
      thoracic duct embolization or interruption for the treatment of high-output chyle
      leak caused by injury to the thoracic duct. RESULTS: A total of 106 patients
      presented with chylothorax, 1 patient presented with chylopericardium, and 2
      patients presented with cervical lymphocele. Twenty patients (18%) had previous
      failed thoracic duct ligation. In 108 of 109 patients, a lymphangiogram was
      successful. Catheterization of the thoracic duct was achieved in 73 patients
      (67%). In 71 of these 73 patients, embolization of the thoracic duct was
      performed. Endovascular coils or liquid embolic agent was used to occlude the
      thoracic duct. In 18 of 33 cases of unsuccessful catheterization, thoracic duct
      needle interruption was attempted below the diaphragm. Resolution of the chyle
      leak was observed in 64 of 71 patients (90%) post-embolization. Needle
      interruption of the thoracic duct was successful in 13 of 18 patients (72%). In
      17 of the 20 patients who had previous attempts at thoracic duct ligation,
      embolization or interruption was attempted and successful in 15 (88%). The
      overall success rate for the entire series was 71% (77/109). There were 3 (3%)
      minor complications. CONCLUSION: Catheter embolization or needle interruption of
      the thoracic duct is safe, feasible, and successful in eliminating a high-output
      chyle leak in the majority (71%) of patients. This minimally invasive, although
      technically challenging, procedure should be the initial approach for the
      treatment of a traumatic chylothorax.

PMID- 20042202
TI  - Preoperative very short-term, high-dose erythropoietin administration diminishes
      blood transfusion rate in off-pump coronary artery bypass: a randomized blind
      controlled study.
AB  - OBJECTIVE: Human recombinant erythropoietin has been used to obtain a rapid
      increase in red blood cells before surgery. Previously, the shortest preparatory
      interval has been 4 days, but at the European Hospital only 2.4 days on average
      separate hospitalization and surgery. We therefore proposed a randomized blind
      trial to test the efficacy of high-dose erythropoietin for very short-term
      administration. METHODS: All patients presenting with a diagnosis of isolated
      coronary vessel disease were randomized to either erythropoietin therapy or a
      control group. Patients with a creatinine level greater than 2 mg/dL or
      hemoglobin level greater than 14.5 g/dL were excluded. Hemoglobin values were
      collected preoperatively and on postoperative days 1 and 4. Blood loss and blood
      transfusion rate were recorded at the time of discharge. RESULTS: We enrolled 320
      consecutive patients in the study. No significant difference was found in
      preoperative parameters, postoperative blood loss, or mean preoperative
      hemoglobin levels. On postoperative day 4, mean hemoglobin was 15.5% higher in
      the erythropoietin group (10.70 +/- 0.72 g/dL vs 9.26 +/- 0.71 g/dL; P < .05).
      This group required 0.33 units of blood per patient, whereas the controls
      required 0.76 units per patient (risk ratio 0.43, P = .008). CONCLUSION: A
      significant reduction in transfusion rate and a significant increase in
      hemoglobin values were observed in the erythropoietin group. No adverse events
      related to erythropoietin administration were recorded. A very short preoperative
      erythropoietin administration seems to be a safe and easy method to reduce the
      need for blood transfusions.

PMID- 20042203
TI  - Free and bound polybrominated diphenyl ethers and tetrabromobisphenol A in
      freshwater sediments.
AB  - Both free and bound fractions of polybrominated diphenyl ethers (PBDEs) and
      tetrabromobisphenol A (TBBPA) in sediment were examined. The free fraction was
      operationally defined as the fraction of each target compound extracted with a
      solvent mixture of hexane/acetone by Soxhlet extraction, while the bound fraction
      was the portion released from the sediments by alkaline hydrolysis following the
      solvent extractions. Tri- to hepta-BDEs and TBBPA were detected in the bound
      fraction. Bound PBDEs accounted for 0.2-2.8% of the total PBDEs and bound TBBPA
      accounted for 6.5-48% of the total TBBPA, in surface sediments. In sediment
      cores, these percentages ranged from 1.8% to 42% for bound PBDEs and 22-92% for
      bound TBBPA. The percentages of bound materials showed an increasing trend with
      the sediment depth. Sequestration of PBDEs and TBBPA within sediments might be an
      important geochemical fate of these brominated flame retardants.

PMID- 20042204
TI  - Metal concentration and structural changes in Corallina elongata (Corallinales,
      Rhodophyta) from hydrothermal vents.
AB  - Shallow-water hydrothermal activity is widely present at Azores archipelago.
      Organisms in such environments present great potential as sentinels of the
      effects derived from chronically exposure to increased temperature, metal
      concentrations and reduced pH. This study aimed to evaluate metal concentration
      in Corallina elongata collected at locations exposed and not exposed to shallow
      water hydrothermal activity and evaluate changes in its calcareous structure.
      Elemental concentration was determined and morphometric analysis was performed by
      scanning electron microscopy. Thicker cell walls and a bleached appearance were
      observed on C. elongata specimens from the hydrothermally active location, as
      well as increased concentrations of elements associated to volcanic activity.
      This study reports on metal accumulation and morphometric changes in the
      calcareous structure of C. elongata from a hydrothermally active location, adding
      new data for further research on such habitats and communities, providing an
      insight on how coralline algae might be affected by ocean acidification.

PMID- 20042205
TI  - [Antifungal prophylaxis in oncohematologic patients: Literature review and
      recommendations].

PMID- 20042206
TI  - [Familial hemophagocytic lymphohistiocytosis: Neuroradiological findings].
AB  - Hemophagocytic lymphohistiocytosis (HL) is a rare syndrome, although more common
      in children, that may be underdiagnosed. The clinical presentation can be
      aggressive, and patients may rapidly develop lethal multiple organ failure....HL
      simulates the presentation of infectious sepsis, although the response to
      treatment and evolution are worse. HL should be suspected in young children with
      persistent fever of unknown origin, general malaise, hepatosplenomegaly,
      cytopenia, elevated triglycerides and ferritin, and decreased fibrinogen. Brain
      MRI shows diffuse leptomeningeal and perivascular enhancement, patchy areas of
      hyperintensity in the white matter of both cerebral hemispheres on T2-weighted
      sequences, and cerebral atrophy. Diffusion-weighted sequences are useful for
      staging the lesions. We present a fatal case of familial HL and review the
      literature about the clinical, histological, and radiological characteristics of
      this disease.

PMID- 20042207
TI  - Cryoablation induces greater inflammatory and coagulative responses than
      radiofrequency ablation or laser induced thermotherapy in a rat liver model.
AB  - BACKGROUND: Cryoablation (CA), radiofrequency ablation (RFA), and laser induced
      thermotherapy (LITT) are alternative therapies for patients with unresectable
      liver tumors. We investigated whether there are different inflammatory and
      coagulative responses between these techniques. METHODS: Livers of 48 rats were
      subjected to either CA, RFA, LITT, or sham operation (n = 12 in each group).
      Blood was withdrawn before, and 1, 3, 6, and 24 h after ablation. Liver enzymes
      as well as inflammatory and coagulation parameters were determined. Whole liver
      sections from the coagulated liver lobe were stained for quantification of
      necrosis and morphologic examination. RESULTS: Histologic examination showed
      similar volume of complete destruction of liver parenchyma after CA, RFA, or
      LITT. Transaminase levels as well as the inflammatory response upon CA, as
      reflected by white blood cell count and cytokine levels, were significantly
      higher than following RFA or LITT. The systemic intravascular procoagulative
      state in rats that underwent CA, as reflected by platelets, and levels of
      sensitive markers for activation of coagulation and fibrinolyis, was also
      significantly higher. CONCLUSION: CA of liver in rats induces greater
      inflammatory and coagulative responses than RFA or LITT. The combined activation
      of inflammation and coagulation may importantly contribute to the higher
      morbidity after CA.

PMID- 20042209
TI  - Accelerated evolution of SIV env within the cerebral compartment in the setting
      of morphine-dependent rapid disease progression.
AB  - Human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV)
      have been shown to compartmentalize within various tissues, including the brain.
      However, the evolution of viral quasispecies in the setting of drug abuse has not
      been characterized. The goal of this study was to examine viral evolution in the
      cerebral compartment of morphine-dependent and control macaques to determine its
      role in rapid disease progression. To address this issue, we analyzed the
      envelope (env) gene from proviral DNA in our SIV/SHIV macaque model of morphine
      dependence and AIDS. Analyses of proviral DNA revealed a direct correlation
      between total genetic changes and survival time. However, the rate of evolution
      during disease progression was higher in morphine-dependent and rapid-progressor
      macaques than was the rate of evolution in the control animals. This study
      provides additional insight into SIV envelope variation in the CNS of morphine
      dependent macaques and genotypes that may have evolved in the brain and
      contributed to disease progression.

PMID- 20042211
TI  - Kinetics and intracellular location of intramolecular disulfide bond formation
      mediated by the cytoplasmic redox system encoded by vaccinia virus.
AB  - Poxviruses encode a redox system for intramolecular disulfide bond formation in
      cytoplasmic domains of viral proteins. Our objectives were to determine the
      kinetics and intracellular location of disulfide bond formation. The vaccinia
      virus L1 myristoylated membrane protein, used as an example, has three
      intramolecular disulfide bonds. Reduced and disulfide-bonded forms of L1 were
      distinguished by electrophoretic mobility and reactivity with monoclonal and
      polyclonal antibodies. Because disulfide bonds formed during 5 min pulse labeling
      with radioactive amino acids, a protocol was devised in which dithiothreitol was
      present at this step. Disulfide bond formation was detected by 2 min after
      removal of reducing agent and was nearly complete in 10 min. When the penultimate
      glycine residue was mutated to prevent myristoylation, L1 was mistargeted to the
      endoplasmic reticulum and disulfide bond formation failed to occur. These data
      suggested that viral membrane association was required for oxidation of L1,
      providing specificity for the process.

PMID- 20042210
TI  - An improved reverse genetics system for mammalian orthoreoviruses.
AB  - Mammalian orthoreoviruses (reoviruses) are highly useful models for studies of
      double-stranded RNA virus replication and pathogenesis. We previously developed a
      strategy to recover prototype reovirus strain T3D from cloned cDNAs transfected
      into murine L929 fibroblast cells. Here, we report the development of a second
      generation reovirus reverse genetics system featuring several major improvements:
      (1) the capacity to rescue prototype reovirus strain T1L, (2) reduction of
      required plasmids from 10 to 4, and (3) isolation of recombinant viruses
      following transfection of baby hamster kidney cells engineered to express
      bacteriophage T7 RNA polymerase. The efficiency of virus rescue using the 4
      plasmid strategy was substantially increased in comparison to the original 10
      plasmid system. We observed full compatibility of T1L and T3D rescue vectors when
      intermixed to produce a panel of T1LxT3D monoreassortant viruses. Improvements to
      the reovirus reverse genetics system enhance its applicability for studies of
      reovirus biology and clinical use.

PMID- 20042212
TI  - Valuing the subsurface pathogen treatment barrier in water recycling via aquifers
      for drinking supplies.
AB  - A quantitative microbial risk assessment (QMRA) was performed at four managed
      aquifer recharge (MAR) sites (Australia, South Africa, Belgium, Mexico) where
      reclaimed wastewater and stormwater is recycled via aquifers for drinking water
      supplies, using the same risk-based approach that is used for public water
      supplies. For each of the sites, the aquifer treatment barrier was assessed for
      its log(10) removal capacity much like for other water treatment technologies.
      This information was then integrated into a broader risk assessment to determine
      the human health burden from the four MAR sites. For the Australian and South
      African cases, managing the aquifer treatment barrier was found to be critical
      for the schemes to have low risk. For the Belgian case study, the large treatment
      trains both in terms of pre- and post-aquifer recharge ensures that the risk is
      always low. In the Mexico case study, the risk was high due to the lack of pre
      treatment and the low residence times of the recharge water in the aquifer. A
      further sensitivity analysis demonstrated that human health risk can be managed
      if aquifers are integrated into a treatment train to attenuate pathogens.
      However, reduction in human health disease burden (as measured in disability
      adjusted life years, DALYs) varied depending upon the number of pathogens in the
      recharge source water. The beta-Poisson dose response curve used for translating
      rotavirus and Cryptosporidium numbers into DALYs coupled with their slow
      environmental decay rates means poor quality injectant leads to aquifers having
      reduced value to reduce DALYs. For these systems, like the Mexican case study,
      longer residence times are required to meet their DALYs guideline for drinking
      water. Nevertheless the results showed that the risks from pathogens can still be
      reduced and recharging via an aquifer is safer than discharging directly into
      surface water bodies.

PMID- 20042213
TI  - Disinfection by-product formation of natural organic matter surrogates and
      treatment by coagulation, MIEX and nanofiltration.
AB  - Potentially the most effective means of controlling disinfection by-products
      (DBPs) is to remove precursors before disinfection. To understand relationships
      between physical properties, treatability and DBP formation, nine natural organic
      matter (NOM) surrogates were studied. Their DBP formation and removal by
      coagulation, MIEX anion exchange resin and two nanofiltration membranes was
      measured. Whereas treatability of NOM surrogates was explained in terms of their
      physicochemical properties, the same was not true of DBP formation. Hence it was
      not possible to selectively remove compounds which generate high amounts of DBPs.
      Instead, precursor removal strategies based upon empirical DBP formation
      potential testing are more apt. Under conditions simulating full-scale
      performance, MIEX did not offer improved performance over coagulation. A
      hydrophobic nanofiltration membrane proved successful for removing neutral,
      hydrophilic surrogates, and hence is also suitable for DBP precursors of this
      character.

PMID- 20042214
TI  - The impact of barley straw conditioning on the inhibition of Scenedesmus using
      chemostats.
AB  - The current paper investigates the role of barley straw conditioning on
      inhibiting the alga Scenedesmus. Fresh, pre-rotted and white rot fungi (WRF)
      augmented straw was tested in a series of chemostat experiments over 15 weeks.
      All three systems were effective at inhibiting the alga with differences observed
      in the lag time before inhibition occurred and the rate of alga decline. Lag
      times of 8, 4 and 1 week(s) were recorded for the fresh, rotted and fungi-treated
      straws, respectively, with a maximum inhibition rate of >7x10(4) cellsweek(-1)
      observed for the fungi pre-treated system. Overall, the results indicate that pre
      treatment is a viable method to enable barley straw to be used in a more reactive
      manner. Explanation is postulated that during pre-treatment no alternative
      sources of nitrogen are available, thereby leading to greater bacterial
      decomposition of straw lignin to release inhibitory substances. The principle of
      utilising an engineered pre-treatment by inoculating barley straw with WRF to
      enhance the impact of the straw on algal inhibition has been clearly
      demonstrated. Further work is required to understand how the straw pre-treatment
      stage can be reduced to minimise its duration while maximising the inhibitory
      effect of adding barley straw.

PMID- 20042215
TI  - Colloid dispersion on the pore scale.
AB  - Dispersion describes the spreading of a tracer or contaminant in an aquifer.
      Detailed knowledge of dispersion is the key to successful risk assessment in case
      of groundwater pollution or groundwater protection. The dispersion of colloids on
      the pore scale is controlled by flow velocity, ionic strength, colloid size,
      colloid concentration, and colloid-matrix interactions. The objective of this
      study was to provide quantitative data and to assess the scale dependency of
      colloid dispersion on the pore scale. The positions of carboxylated polystyrene
      microspheres (1 microm, 0.5 microm) were recorded during transport experiments in
      silicon micromodels with three pore topologies. The positions were combined into
      particle trajectories revealing the flow path of individual colloids. More than
      thousand trajectories were evaluated for each experiment to obtain the
      dispersivity of the colloids for flow distances between 10 and 1000 microm. All
      experiments were run at high Peclet numbers. The pore scale dispersivity was on
      the order of 8-30% of the flow distance with pure water, dependent on the
      heterogeneity of the pore topology. The dispersivity was positively correlated
      with the ionic strength and inversely correlated with the colloid size and the
      flow velocity. A coating of the micromodel surface with humic acid also increased
      dispersivity. The quantitative data set presented here supports the theoretical
      framework for colloid transport and allows to parametrize colloid transport on
      the pore scale.

PMID- 20042216
TI  - Synthesis and evaluation of the platelet antiaggregant properties of phenolic
      antioxidants structurally related to rosmarinic acid.
AB  - Polyphenols, such as rosmarinic acid, are widely distributed natural products
      with relevant antioxidant activity. Oxidative stress plays an important role in
      the pathogenesis of a number of disorders. Here, we report on the synthesis and
      biological effects of the polyphenolic esters hydroxytyrosyl gallate (1),
      hydroxytyrosyl protocatechuate (2) and hydroxytyrosyl caffeate (3), structurally
      related to rosmarinic acid. The three compounds showed a greater free radical
      scavenging activity than their precursors and also than rosmarinic acid. Esters 1
      and 3 significantly reduced thrombin-evoked platelet aggregation, which is likely
      mediated to the attenuation of thrombin-stimulated Ca(2+) release and entry. The
      three compounds reduced the ability of platelets to accumulate Ca(2+) in the
      intracellular stores, probably by enhancing the Ca(2+) leakage rate and reduced
      store-operated Ca(2+) entry in these cells. These observations suggest that the
      structurally-simplified analogs to rosmarinic acid, compounds 1 and 3, might be
      the base of therapeutic strategies to prevent thrombotic complications associated
      to platelet hyperaggregability due to oxidative stress.

PMID- 20042217
TI  - Aerobic biodegradation of cis-1,2-dichloroethene as sole carbon source: Stable
      carbon isotope fractionation and growth characteristics.
AB  - Cis-1,2-dichloroethene (cDCE) is a compound of concern at many chloroethene
      contaminated sites, since it tends to accumulate during reductive dechlorination
      of the higher chlorinated ethenes. Stable carbon isotope fractionation during
      aerobic cDCE biodegradation was observed in groundwater microcosms under varying
      incubation conditions (room temperature/groundwater temperature; with/without
      inorganic nutrients), and resulted in an average stable carbon isotope enrichment
      factor of -15.2+/-0.5 per thousand. A new enrichment culture, obtained from
      groundwater microcosms, degraded cDCE concentrations up to 100mgL(-1), was active
      at temperatures between 4 and 23 degrees C, had a pH optimum of approximately 7,
      and could withstand prolonged periods (250d) of starvation. Microbial growth
      during degradation of cDCE as sole carbon and energy source was demonstrated by
      protein formation in mineral medium not containing any known auxiliary substrate.
      The obtained growth yield was 12.5+/-1.9g of proteinMol(-1) of cDCE, with a
      doubling time of 53+/-2h at 23 degrees C. Aerobic degradation of cDCE as sole
      carbon and energy source appears to be a promising biological process for site
      remediation.

PMID- 20042218
TI  - Sorption of perfluorooctane sulfonate on organo-montmorillonites.
AB  - Perfluorinated compound as one of the emerging pollutants has caused great
      attention in recent years. In this study, the organo-montmorillonites (organo
      Mts) with different amounts and arrangements of hexadecyltrimethylammonium
      bromide (HDTMAB) were prepared as effective sorbents for PFOS removal from water.
      Batch sorption experiments including sorption kinetics, sorption isotherm as well
      as effect of solution pH were studied. The Elovich and pseudo-second-order models
      were selected to fit the kinetic data and the latter described the sorption
      kinetic better. Sorption isotherms showed that the sorption amount of PFOS
      increased with increasing amount of HDTMAB loaded in the montmorillonites,
      indicating that hydrophobic interaction played an important role in the sorption
      process. Comparative sorption of other perfluorinated compounds (PFCs) with
      different length of C-F chains and different functional groups further verified
      that hydrophobic interaction was the main force for the sorption of PFCs on the
      organo-Mts. X-ray diffraction (XRD) analysis demonstrated the significant
      decrease of interlayer distance after PFOS sorption, suggesting that the HDTMAB
      molecules were rearranged in the interlayer of organo-Mts. The PFOS molecules
      first diffused into the organo-Mts via hydrophobic interaction, and then the
      rearrangement occurred through electrostatic interaction between the two
      surfactants, resulting in the microstructure change within the organo-Mts.

PMID- 20042219
TI  - Influence of humic acid type on the oxidation products of pentachlorophenol using
      hybrid catalysts prepared by introducing iron(III)-5,10,15,20-tetrakis(p
      hydroxyphenyl) porphyrin into hydroquinone-derived humic acids.
AB  - An iron(III)-5,10,15,20-tetrakis(p-hydroxyphenyl) porphyrin (FeTHP) was
      introduced into hydroquinone-derived humic acids via formaldehyde
      polycondensation. The influence of humic acid (HA) type on the catalytic
      oxidation of pentachlorophenol (PCP) was investigated using two HAs as follows:
      Shinshinotsu peat (SHA) with a lower carboxylic acid content; Tohro ando soil
      (THA) with a higher carboxylic acid content. The levels of PCP degradation and
      dechlorination for the catalysts prepared using SHA (SHA-FeTHP) and THA (THA
      FeTHP) were significantly higher than those for FeTHP. In terms of oxidation
      products, the more toxic dimer, octachlorodibenzo-p-dioxin (OCDD), was not
      produced in the case of the SHA-FeTHP system, while 4-7% of the PCP was converted
      to OCDD when the FeTHP and THA-FeTHP catalytic systems were used. These results
      indicate that a catalyst prepared using SHA is more active, in terms of the
      detoxification of PCP, than other catalysts. Comparisons of UV-Vis absorption
      spectra before and after the catalytic oxidation showed that the Soret band for
      SHA-FeTHP clearly remained after a 30-min incubation period, while the intensity
      of the majority of Soret bands for FeTHP and THA-FeTHP were rapidly reduced after
      a 5-min incubation period. These results suggest that the SHA-FeTHP is a stable
      catalyst, and this stability results in a more extensive oxidation of the more
      toxic byproducts.

PMID- 20042220
TI  - Low-temperature selective catalytic reduction of NO with NH(3) over Mn-Ce oxides
      supported on TiO2 and Al2O3: a comparative study.
AB  - MnCe oxides were supported on TiO(2) and Al(2)O(3) by an ultrasonic impregnation
      method and used for selective catalytic reduction (SCR) of NO with NH(3) at low
      temperature (80-220 degrees C). MnCe/TiO(2) showed a relatively higher SCR
      activity than MnCe/Al(2)O(3) at the temperature range of 80-150 degrees C. When
      the reaction temperature was higher than 150 degrees C, MnCe/Al(2)O(3) exhibited
      superior SCR activity to MnCe/TiO(2). NH(3) temperature programmed desorption
      study proved that MnCe/TiO(2) was mainly Lewis acidic, while MnCe/Al(2)O(3) could
      provide more Bronsted acid sites. These acid sites play an important role in SCR
      according to in situ diffuse reflectance infrared transform spectroscopy (DRIFT)
      analysis. The main SCR reaction was a typical Eley-Rideal mechanism on
      MnCe/TiO(2), which took place between coordinated NH(3)/NH(4)(+) and gas-phase
      NO. For MnCe/Al(2)O(3), the reaction mainly occurred via another pathway when the
      temperature exceeded 150 degrees C, which commenced with the adsorption and
      oxidation of NO and was followed by reaction between NO(2) or NO(2)-containing
      compounds and NH(3) adspecies. This reaction pathway makes a significant
      contribution to the improved NO conversion for MnCe/Al(2)O(3) at higher
      temperature.

PMID- 20042221
TI  - Comparative analysis of whole sediment and porewater toxicity identification
      evaluation techniques for ammonia and non-polar organic contaminants.
AB  - Porewater and whole sediment toxicity identification evaluations (TIEs) were
      performed on contaminated Illinois River sediment and compared using two
      standardized toxicity-testing organisms (Ceriodaphnia dubia and Hyalella azteca).
      Results suggested that the choice of testing matrix (porewater versus whole
      sediment) significantly influenced characterization of toxicity. The porewater
      TIE suggested that ammonia was the major source of toxicity, while the whole
      sediment TIE indicated that non-polar organics, specifically polycyclic aromatic
      hydrocarbons, were the primary contributor to toxicity, with ammonia being a
      secondary contributor to toxicity. While the choice of test organism may have
      played a smaller role in the discordance between the TIEs, the data suggest that
      this factor alone could play a prevalent role in characterizing toxicity in other
      TIE assessments. Because porewater and whole sediment TIEs examine sediment
      toxicity differently, using both TIE approaches as part of a risk assessment may
      provide a more accurate risk estimate of sediment toxicity.

PMID- 20042222
TI  - Occurrence of organochlorine pesticide residues in eggs, chicken and meat in
      Jordan.
AB  - Organochlorine pesticide (OCP) residues in 519 samples; comprising eggs, chicken
      and meat (lamb and beef), collected from Jordan were determined. All samples were
      analyzed for their residual contents of aldrin, dichlorodiphenyltrichloroethane
      and metabolites (DDTs), dieldrin, endosulfan isomers, endrin,
      hexachlorocyclohexane isomers (HCHs), heptachlor, heptachlor epoxide and
      hexachlorobenzene (HCB). The samples were Soxhlet extracted for 8h in 250mL
      petroleum ether. The cleanup of the samples was performed by Florisil column
      chromatography and analysis was done on a gas chromatography equipped with an
      electron capture detector (GC-ECD). The results indicated that 28% (38/134), 20%
      (23/115) and 49% (131/270) of the examined eggs, chicken and meat samples,
      respectively, were contaminated with OCP residues. HCHs and DDTs are the most
      prominently noticed compounds, as they were detected at a high incidence. On the
      other hand, heptachlor, heptachlor epoxide, HCB, aldrin and endrin compounds were
      only present in less than 7% of the analyzed samples. These residues are present
      despite complete ban on the use of OCPs for agricultural purposes in Jordan. No
      residues of op'-DDD, op'-DDT, dieldrin, alpha-endosulfan and beta-endosulfan were
      detected.

PMID- 20042223
TI  - Bone remodeling of the Homo heidelbergensis mandible; the Atapuerca-SH sample.
AB  - Growth by bone remodeling is one of the key mechanisms responsible for skeletal
      morphology. This mechanism consists of the coordinated activity of two cellular
      groups: osteoblasts and osteoclasts, which are responsible for bone deposition
      and resorption, respectively. Information obtained from the study of these
      remodeling growth fields allows us to understand how species-specific
      craniofacial form is achieved. These data can help to explain the facial growth
      differences among Primates, both extinct and extant. The aim of this study was to
      obtain the distribution of growth remodeling fields of the Homo heidelbergensis
      mandible (Atapuerca-SH sample), and to infer the growth processes responsible for
      its specific morphology. A Reflected Light Microscope (RLM) was used to identify
      the microfeatures of the bone surface related to bone deposition and resorption.
      Results show that H. heidelbergensis presents a specific growth field
      distribution, which differs slightly between immature and adult individuals.
      Interpretation of these maps indicates that the mandible of H. heidelbergensis
      presents noteworthy variability in the symphyseal region. Two distinct patterns
      of growth are seen, one of those unique for this species and the other similar to
      that of Homo sapiens. The lingual side of the mandibular corpus has a resorption
      area found only in this species and one that includes a variable extension in
      immature and adult individuals. Finally, the mandibular ramus is characterized,
      among other aspects, by a large resorption field on its buccal surface.
      Considering the mandible as a whole, the bone remodeling pattern obtained in this
      work shows that lower facial growth in H. heidelbergensis is dominated mainly by
      forward growth, illustrated by the strong inward displacement of the ramus, which
      is in agreement with the Enlow's "V" growth principle.

PMID- 20042224
TI  - 500,000 year old blades from the Kapthurin Formation, Kenya.

PMID- 20042225
TI  - Addressing clinical trials: can the multidisciplinary Tumor Board improve
      participation? A study from an academic women's cancer program.
AB  - OBJECTIVE: The Tumor Board (TB) allows for an interdisciplinary approach to
      cancer treatment designed to encourage evidence-based treatment. However, its
      role in facilitating clinical trial participation has not been reported. We aimed
      to determine whether a prospective TB is an effective strategy for trial
      recruitment and to identify steps within the TB process that facilitate
      discussion of trial eligibility and optimize accrual. METHODS: We conducted a
      retrospective cross-sectional analysis of women presented to Gynecologic Oncology
      TB between March and December 2008. Patient demographics, TB recommendations, and
      post-TB patient discussions were abstracted. These were compared to data derived
      from the Department of Oncology Research to determine research team awareness of
      eligible patients and confirm trial enrollment(s). Data analysis was completed
      with Chi-square test; risk ratios and confidence intervals were calculated as
      summary measures. RESULTS: We reviewed 1213 case presentations involving 916
      women. Overall, 358 TB recommendations (30%) identified eligible patients, of
      which enrollment consisted of 87 (24%) trials (6% therapeutic trials and 18% non
      therapeutic trials). Compared to other types of TB recommendations, those
      involving trials were discussed less frequently at post-TB patient visits (79%
      vs. 44%). Documentation of trial discussion at the post-TB visit was more likely
      to result in trial participation, versus solely relying on the research staff to
      communicate enrollment eligibility with the treating team (RR 2.5, p=0.006).
      CONCLUSIONS: Patients identified by the TB were 2.5-times as likely to enroll in
      a clinical trial, but trials were mentioned only 44% of the time. Interventions
      that facilitate trial discussions during post-TB meetings are needed to improve
      trial participation.

PMID- 20042226
TI  - Does the use of diagnostic PET/CT cause stage migration in patients with primary
      advanced ovarian cancer?
AB  - OBJECTIVE: To investigate if the use of diagnostic FDG-PET/CT leads to stage
      migration in patients with advanced ovarian cancer and to evaluate the prognostic
      significance of FDG-PET/CT. METHODS: From September 2004 to August 2007, 201
      patients with a Risk of Malignancy Index (RMI) >150 based on serum CA-125,
      ultrasound examinations and menopausal state, underwent PET/CT within 2 weeks
      prior to standard surgery/debulking of a pelvic tumor. On 15 August, 2009 overall
      survival and prognostic variables were analysed in 66 ovarian cancer patients (64
      stage III and 2 stage IV). RESULTS: Median follow-up was 30.2 months; median age
      was 62.5 years (range 35-85 years); 97% (64/66) had a performance status <or=2;
      38% (25/66) underwent complete debulking (no macroscopic residual tumor); 51%
      (39/66) was diagnosed with PET/CT stage III and 41% (27/66) was diagnosed with
      PET/CT stage IV. Survival was significantly longer for patients with PET/CT stage
      III than for patients with PET/CT stage IV (P=0.03). Using univariate analysis,
      PET/CT stage III (P=0.03), complete debulking (no macroscopic residual tumor)
      (P=0.002), and GOG performance status <or=2 (P=0.04) were statistically
      significant prognostic variables. Using multivariate Cox regression analysis,
      complete debulking was the only statistically significant independent prognostic
      variable (P=0.02). CONCLUSION: In primary advanced ovarian cancer the use of
      diagnostic FDG-PET/CT leads to stage migration. Adequate staging is the
      foundation for ovarian cancer treatment and advanced imaging for optimal
      evaluation of metastases should be promoted in clinical trials. The strongest
      determinant of patient outcome is residual abdominal tumor after primary surgery.

PMID- 20042228
TI  - Primary immunodeficiencies.
AB  - In the last years, advances in molecular genetics and immunology have resulted in
      the identification of a growing number of genes causing primary
      immunodeficiencies (PIDs) in human subjects and a better understanding of the
      pathophysiology of these disorders. Characterization of the molecular mechanisms
      of PIDs has also facilitated the development of novel diagnostic assays based on
      analysis of the expression of the protein encoded by the PID-specific gene. Pilot
      newborn screening programs for the identification of infants with severe combined
      immunodeficiency have been initiated. Finally, significant advances have been
      made in the treatment of PIDs based on the use of subcutaneous immunoglobulins,
      hematopoietic cell transplantation from unrelated donors and cord blood, and gene
      therapy. In this review we will discuss the pathogenesis, diagnosis, and
      treatment of PIDs, with special attention to recent advances in the field.

PMID- 20042227
TI  - Secondary immunodeficiencies, including HIV infection.
AB  - Extrinsic factors can adversely affect immune responses, producing states of
      secondary immunodeficiency and consequent increased risk of infections. These
      immunodeficiencies, which can be encountered in routine clinical practice, arise
      from a number of conditions, such as treatment with glucocorticoids and
      immunomodulatory drugs, surgery and trauma, extreme environmental conditions, and
      chronic infections, such as those caused by HIV. The most common cause of
      immunodeficiency is malnutrition, affecting many communities around the world
      with restricted access to food resources. Protein-calorie deficiency and
      micronutrient deficiencies have been shown to alter immune responses; of note,
      recent progress has been made in the influence of vitamin D deficiency in causing
      failure of immune activation. Other categories of disease that might present with
      secondary immunodeficiency include metabolic diseases and genetic multisystemic
      syndromes. The immune defects observed in secondary immunodeficiency are usually
      heterogeneous in their clinical presentation, and their prognosis depends on the
      severity of the immune defect. Management of the primary condition often results
      in improvement of the immunodeficiency; however, this is sometimes not possible,
      and the risk of infections can be reduced with prompt antimicrobial treatment and
      prophylaxis.

PMID- 20042229
TI  - Josiah F. Wedgwood (1950-2009).

PMID- 20042231
TI  - Food allergy.
AB  - Adverse immune responses to foods affect approximately 5% of young children and
      3% to 4% of adults in westernized countries and appear to have increased in
      prevalence. Food-induced allergic reactions are responsible for a variety of
      symptoms and disorders involving the skin and gastrointestinal and respiratory
      tracts and can be attributed to IgE-mediated and non-IgE-mediated (cellular)
      mechanisms. Genetic disposition and environmental factors might abrogate oral
      tolerance, leading to food allergy. Disease outcomes are influenced by the
      characteristics of the immune response and of the triggering allergen. Diagnosis
      is complicated by the observation that detection of food-specific IgE
      (sensitization) does not necessarily indicate clinical allergy. Therefore
      diagnosis requires a careful medical history, laboratory studies, and, in many
      cases, an oral food challenge to confirm a diagnosis. Novel diagnostic methods,
      including ones that focus on immune responses to specific food proteins or
      epitopes of specific proteins, are under study. Currently, management of food
      allergies consists of educating the patient to avoid ingesting the responsible
      allergen and to initiate therapy (eg, with injected epinephrine for anaphylaxis)
      in case of an unintended ingestion. Improved therapeutic strategies under study
      include oral and sublingual immunotherapy, Chinese herbal medicine, anti-IgE
      antibodies, and modified vaccines.

PMID- 20042230
TI  - Laboratory evaluation of primary immunodeficiencies.
AB  - Primary immunodeficiencies are congenital disorders caused by defects in
      different elements of the immune system. Affected patients usually present
      clinically with recurrent infections, severe infections, or both, as well as
      autoimmune phenomena that are associated with many of these disorders. Early
      diagnosis is essential for referral to specialized care centers and the prompt
      initiation of appropriate therapy. In this article the authors describe a general
      approach for the investigation of the most common primary immunodeficiencies,
      outlining the typical clinical symptoms and most appropriate laboratory
      investigations.

PMID- 20042232
TI  - The expression of angiogenic growth factors and their receptors in ovarian
      follicles throughout the estrous cycle in the ewe.
AB  - Healthy follicles are highly vascularized whereas those undergoing atresia have
      poor vascularity, suggesting a relationship between follicular vascularization
      and follicular function. Vascularization is regulated by angiogenic factors, and
      among them vascular endothelial growth factor (VEGF) and angiopoietin-Tie (Ang
      Tie) systems are of central importance. The objectives of this study were to
      determine if VEGF, VEGF receptor-2 (VEGFR-2), and components of the Ang-Tie
      system are expressed in ovarian follicles at both the protein and mRNA levels and
      to explore if their expression is related to the stage of the estrous cycle in
      the ewe. Ovaries from cyclic ewes were collected during the luteal phase (n=5) or
      before (n=5), during (n=4), and after (n=4) the preovulatory luteinizing hormone
      (LH) surge. After fixation, ovaries were wax-embedded, serially sectioned, and
      analyzed for both protein and mRNA expression of VEGF, VEGFR-2, angiopoietin-1
      (Ang-1), angiopoietin-2 (Ang-2), Tie-1 (mRNA only), and Tie-2. mRNA was studied
      by in situ hybridization using digoxigenin-11-UTP-labeled ovine riboprobes. A
      similar pattern of expression was observed for mRNA and protein for all of the
      factors. Both mRNA and protein expression of VEGF, VEGFR-2, Ang-1, Ang-2, Tie-1
      (mRNA only), and Tie-2 in the granulosa and theca cells of follicles >or=2mm in
      diameter was significantly different among the stages of the estrous cycle, with
      the highest expression detected at the post-LH surge stage. Theca cells expressed
      significantly greater levels of the six angiogenic factors compared with
      granulosa cells at all stages of the estrous cycle. Expression levels in
      granulosa and theca cells were comparable between small (2.0 to 2.5mm) and medium
      (2.5 to 4.0mm) follicles, but large follicles (>4.0mm) expressed higher mRNA and
      protein levels (all P<0.05) for all factors at all stages of the estrous cycle.
      These data show (i) that VEGF, VEGFR-2, and the Ang-Tie system are present in
      both granulosa and theca cells of the ovarian follicle, (ii) that thecal cells
      consistently express greater levels of all of these factors compared with
      granulosa cells, and (iii) that their levels of expression are related to the
      stage of the estrous cycle and to follicle size.

PMID- 20042233
TI  - Superior temporal activation as a function of linguistic knowledge: insights from
      deaf native signers who speechread.
AB  - Studies of spoken and signed language processing reliably show involvement of the
      posterior superior temporal cortex. This region is also reliably activated by
      observation of meaningless oral and manual actions. In this study we directly
      compared the extent to which activation in posterior superior temporal cortex is
      modulated by linguistic knowledge irrespective of differences in language form.
      We used a novel cross-linguistic approach in two groups of volunteers who
      differed in their language experience. Using fMRI, we compared deaf native
      signers of British Sign Language (BSL), who were also proficient speechreaders of
      English (i.e., two languages) with hearing people who could speechread English,
      but knew no BSL (i.e., one language). Both groups were presented with BSL signs
      and silently spoken English words, and were required to respond to a signed or
      spoken target. The interaction of group and condition revealed activation in the
      superior temporal cortex, bilaterally, focused in the posterior superior temporal
      gyri (pSTG, BA 42/22). In hearing people, these regions were activated more by
      speech than by sign, but in deaf respondents they showed similar levels of
      activation for both language forms - suggesting that posterior superior temporal
      regions are highly sensitive to language knowledge irrespective of the mode of
      delivery of the stimulus material.

PMID- 20042234
TI  - Graft and diblock copolymer multifunctional micelles for cancer chemotherapy and
      imaging.
AB  - Multifunctional mixed micelles that constructed from poly(HEMA-co-histidine)-g
      PLA and diblock copolymer PEG-PLA with functional moiety was developed in this
      study. The mixed micelles had well defined core shell structure which was
      evaluated by TEM. The functional inner core of poly(HEMA-co-histidine)-g-PLA
      exhibited pH stimulate to enable intracellular drug delivery and outer shell of
      PEG-b-PLA with functional moiety Cy5.5 for biodistribution diagnosis and folate
      for cancer specific targeting were synthesized at the end of the polymer chain.
      The graft and diblock copolymer self assembled to nanospheres against water with
      an average diameter below 120 nm without doxorubicin, and an average diameter of
      around 200 nm when loaded with drug. From drug released study, a change in pH
      destroy the inner core to lead a significant doxorubicin(Dox) release from mixed
      micelles. Cellular uptake of folate-micelles was found to be higher than that of
      non-folate-micelles due to the folate-binding effect on the cell membrane,
      thereby providing a similar cytotoxic effect to drug only against the HeLa cell
      line. In vivo study revealed that specific targeting of folate-micelles exhibited
      cancer targeting and efficiency expression on tumor growth, indicating that
      multifunctional micelles prepared from poly(HEA-co-histidine)-g-PLA and folate
      PEG-PLA have great potential in cancer chemotherapy and diagnosis.

PMID- 20042235
TI  - Regeneration of functional nerves within full thickness collagen
      phosphorylcholine corneal substitute implants in guinea pigs.
AB  - Our objective was to evaluate promotion of tissue and nerve regeneration by
      extracellular matrix (ECM) mimics, using corneal implantation as a model system.
      Porcine type I collagen and 2-methacryloyloxyethyl phosphorylcholine (MPC) were
      crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N
      hydroxysuccinimide (NHS) and moulded into appropriate corneal dimensions to serve
      as substitutes for natural corneal ECM. These were implanted as full thickness
      grafts by penetrating keratoplasty into the corneas of guinea pigs after removal
      of the host tissue, and tracked over eight months, by clinical examination, slit
      lamp biomicroscopy, and esthesiometry. Histopathology and ex vivo nerve terminal
      impulse recordings were performed at three months and at eight months. The
      implants promoted regeneration of corneal cells, nerves and the tear film, while
      retaining optical clarity. After three months, electrophysiological recordings
      showed evidence of mechano-nociceptors, and polymodal units inside the implants,
      while cold-sensitive units were present only on the peripheral host cornea.
      Following eight months, the incidence of nerve activity and the frequency of
      spontaneous firing were higher than in control eyes as reported for regenerating
      fibers. Active cold nerve terminals also innervated the implant area. We show
      that ECM mimetic materials can promote regeneration of corneal cells and
      functional nerves. The simplicity in fabrication and demonstrated functionality
      shows potential for ECM substitutes in future clinical applications.

PMID- 20042236
TI  - The attenuation of platelet and monocyte activation in a rabbit model of
      extracorporeal circulation by a nitric oxide releasing polymer.
AB  - Nitric oxide (NO) has been shown to reduce thrombogenicity by decreasing platelet
      and monocyte activation by the surface glycoprotein, P-selectin and the integrin,
      CD11b, respectively. In order to prevent platelet and monocyte activation with
      exposure to an extracorporeal circulation (ECC), a nitric oxide releasing (NORel)
      polymeric coating composed of plasticized polyvinyl chloride (PVC) blended with a
      lipophilic N-diazeniumdiolate was evaluated in a 4 h rabbit thrombogenicity model
      using flow cytometry. The NORel polymer significantly reduced ECC thrombus
      formation compared to polymer control after 4 h blood exposure (2.8 +/- 0.7 NORel
      vs 6.7 +/- 0.4 pixels/cm(2) control). Platelet count (3.4 +/- 0.3 NORel vs 2.3 +/
      0.3 x 10(8)/ml control) and function as measured by aggregometry (71 +/- 3 NORel
      vs 17 +/- 6% control) were preserved after 4 h exposure in NORel versus control
      ECC. Plasma fibrinogen levels significantly decreased in both NORel and control
      groups. Platelet P-selectin mean fluorescence intensity (MFI) as measured by flow
      cytometry was attenuated after 4 h on ECC to ex vivo collagen stimulation (27 +/-
      1 NORel vs 40 +/- 2 MFI control). Monocyte CD11b expression was reduced after 4 h
      on ECC with NORel polymer (87 +/- 14 NORel vs 162 +/- 30 MFI control). These
      results suggest that the NORel polymer coatings attenuate the increase in both
      platelet P-selectin and monocytic CD11b integrin expression in blood exposure to
      ECCs. These NO-mediated platelet and monocytic changes were shown to improve
      thromboresistance of these NORel-polymer-coated ECCs for biomedical devices.

PMID- 20042237
TI  - IFPA Award in Placentology Lecture: Biology of the placental syncytiotrophoblast-
      myths and facts.
AB  - About 15 years ago apoptosis was attributed a role in the development of the
      human placenta. Since then an increasing number of publications has shown that
      programmed cell death plays an essential role in placental growth and
      differentiation, especially in the villous trophoblast. During the last ten years
      a concept was established linking the progress of apoptosis to differentiation of
      cytotrophoblasts and syncytiotrophoblast. Thus, development and maintenance of
      the syncytiotrophoblast depends on the precise orchestration of different
      processes and stages of the apoptosis cascade. This review focuses on the
      maintenance and growth of the syncytiotrophoblast as well as the deportation of
      trophoblast material into the maternal circulation. Nuclear morphology is related
      to transcriptional activity, RNA protection and storage strategies are discussed
      and the differences between syncytial expression rates of RNA and protein are
      highlighted. Moreover, deportation of trophoblast fragments is related to the
      relevant morphological structures (syncytial knots) and to their effects on the
      maternal system. Finally, different modes of release of trophoblast fragments
      such as apoptotic, aponecrotic and necrotic are discussed as being responsible
      for the maternal inflammatory response during pre-eclampsia.

PMID- 20042238
TI  - Gas exchange, antioxidants and foliar injuries in saplings of a tropical woody
      species exposed to ozone.
AB  - Ozone (O(3)) reaches phytotoxical concentrations in the tropics, but the
      sensitivity of tropical plant species to O(3) remains unknown. Visible foliar
      injuries, carbon assimilation (A(sat)), stomatal conductance, superoxide
      dismutase enzyme (SOD) activity and ascorbic acid concentration (AA) were
      evaluated in different-aged leaves of Psidium guajava 'Paluma' saplings. We
      hypothesized that the old leaves are less capable of combating the stress induced
      by O(3) and hence exhibit more severe leaf injuries. Three O(3) exposure
      experiments were performed with 'Paluma' saplings in sites with high O(3)
      concentration and also under filtered air conditions. The exposure experiments
      corresponding to the seasons spring/2006, summer and autumn/2007. The decrease of
      A(sat) was greater in old leaves of saplings exposed to O(3), except in the
      second experiment, when the AA concentrations were more pronounced than in the
      other experiments. In second experiment, O(3) uptake was similar to that of the
      first experiment, but the injuries were less severe, probably due to the high AA
      concentrations. It was not possible to identify a pattern of superoxide dismutase
      enzyme (SOD) activity due to the high variability in the results from O(3)
      exposed and reference saplings. O(3) uptake/A(sat) was higher in leaves
      exhibiting greater injury, suggesting that decrease in A(sat) may have been the
      main feature associated with the visible foliar symptons.

PMID- 20042239
TI  - Psychosocial work environment, interpersonal violence at work and psychotropic
      drug use among correctional officers.
AB  - The aims of this study were to establish the prevalence of psychotropic drug use,
      measure the association between job strain, extrinsic efforts-rewards ratio,
      interpersonal violence and psychotropic drug use among officers working in
      correctional facilities in the province of Quebec in Canada. This study also
      examined if interpersonal violence at work is an intermediate factor in the
      causal chain between psychosocial risk factors at work and psychotropic drug use.
      A cross-sectional study was performed which included 1288 Quebec correctional
      officers. The participants answered a self-administered questionnaire in 2007
      assessing psychological demands, decision latitude, extrinsic efforts, rewards,
      overcommitment, intimidation, psychological harassment, social support in the
      actual job, psychotropic drug use during the month preceding the questionnaire
      and sociodemographic variables. Binomial regressions were performed for the
      principal associations and a bootstrap analysis was performed in order to
      evaluate interpersonal violence as an intermediate factor between psychosocial
      risk factors at work and psychotropic drug use. The prevalence of psychotropic
      drug use among correctional officers was 14.7%. The prevalence ratios (PR) for
      the associations between job strain, extrinsic efforts-rewards ratio, social
      support from colleagues and supervisors, intimidation and psychological
      harassment adjusted for age and gender were respectively 1.4 (95% CI 0.9-2.2),
      1.6 (95% CI 1.2-2.2), 1.7 (95% CI 1.3-2.3), 1.4 (95% CI 0.9-2.4) and 1.5 (95% CI
      1.1-2.0). The value of the indirect effect evaluating psychological harassment as
      an intermediate factor was not statistically significant (value=0.0087, 95% CI 
      0.0033 to 0.0207). An imbalanced extrinsic efforts-rewards ratio, low social
      support from colleagues and supervisors and psychological harassment at work were
      separately associated with psychotropic drug use among correctional officers.
      Psychological harassment was not found to be an intermediate factor.

PMID- 20042241
TI  - Characteristics of hearing impairment in Yemeni children with chronic suppurative
      otitis media: a case-control study.
AB  - BACKGROUND: Chronic suppurative otitis media (CSOM) is a serious disorder
      particularly in low resource settings. It can lead to disabling hearing
      impairment and sometimes life-threatening infective complications. OBJECTIVE: The
      aim of the present study was to describe the characteristics of hearing
      impairment associated with CSOM in Yemeni children. METHODS: A case-control study
      of 75 children with CSOM and 74 healthy controls. Hearing was assessed by
      behavioural testing and audiometry. RESULTS: Cases had lower academic performance
      than controls (OR 15.31, 95% CI 1.99-322.14, p<0.001). Disabling hearing
      impairment >30 dB was present in 51.5% (right ear) and 66.7% (left ear) of
      children with CSOM. CONCLUSION: Disabling hearing impairment was identified as a
      major health problem in these Yemeni children with CSOM. There is a need for
      investment to reduce the burden of CSOM and its complications in these
      communities. Greater attention to the chronic disabling effects of CSOM in
      children is required in poor communities and low resource settings.

PMID- 20042240
TI  - Molecular basis of C-reactive protein binding and modulation of complement
      activation by factor H-related protein 4.
AB  - C-reactive protein (CRP) is a pattern recognition molecule that binds several
      microbial and host ligands. Ligand-bound CRP activates the complement system via
      the classical pathway. Previously, we identified human complement factor H
      related protein 4 (CFHR4), a member of the factor H protein family, as a CRP
      binding protein. Here, we investigated the molecular basis and the functional
      relevance of the interaction of CFHR4 with native CRP. Using recombinantly
      expressed CFHR4 fragments, the CRP binding site was localized to the first short
      consensus repeat (SCR) domain of CFHR4. Peptide arrays identified residues 35-41
      of CFHR4 to be involved in CRP binding. Substitutions of the positively charged
      amino acids of this motif resulted in strongly reduced CRP binding. Sequence
      comparisons revealed that such a motif is not present in the related SCR6 domain
      of factor H, or in the homologous domains of the four other CFHR proteins.
      Homology modelling based on SCR6 of factor H showed that the CRP binding site is
      surface exposed on SCR1 of CFHR4. CFHR4-bound CRP was able to activate
      complement, determined by C3 fragment deposition. Recombinant CFHR4 proteins with
      mutations in the identified binding site showed reduced CRP binding, which in
      turn resulted in reduced complement activation. In summary, these data reveal the
      molecular basis of the specific interaction of CFHR4 with native CRP and suggest
      a role for CFHR4 in enhancing opsonization via CRP binding.

PMID- 20042242
TI  - Qualitative analysis of parents' experience with receiving the news of the
      detection of their child's hearing loss.
AB  - OBJECTIVE: Despite the fact that clinicians are responsible for delivering bad
      news, they have been shown to lack both confidence and skill in performing this
      basic task. The time immediately after the detection of childhood hearing loss is
      perceived as stressful. We conducted a qualitative study to assess parents'
      experiences with receiving the bad news of the detection of their child's hearing
      loss. STUDY DESIGN: Semi-structured interviews were conducted with families of
      children with hearing loss identified during early childhood. SETTING: A
      rehabilitation center treating pre-school children in the north of Israel.
      PATIENTS: 14 families/parents of children diagnosed prior to the implementation
      of a universal screening program. MAIN OUTCOME MEASURE: Parents' perceptions of
      the manner in which the information regarding the detection of their child's
      hearing loss was given, and what their feelings were at the time. RESULTS: 50% of
      parents expressed dissatisfaction with the process of the breaking of the bad
      news. ABR is perceived by parents and health professionals alike as the
      definitive moment of diagnosis. The emotions experienced by parents at the moment
      of the breaking of the bad news were predominantly shock and upset. The meaning
      of the news was perceived differently under different circumstances. Information
      given bluntly, without empathy, was a frequent complaint. Parents repeatedly
      stated the importance of the formulation of a plan for the future. CONCLUSIONS:
      Qualitative enquiry provided valuable information. Effective strategies for the
      breaking of bad news should become an integral part of universal neonatal
      screening programs.

PMID- 20042243
TI  - Saltatory ontogeny of fishes and sensitive early life stages for ecotoxicology
      tests.
AB  - Fish display a wide range of developmental ontogenies. These distinctions have
      taxonomic, evolutionary, and ecological importance in addition to practical
      implications on the use of fish in aquatic toxicity tests. With respect to animal
      welfare, vertebrates are afforded protected or non-protected status in the
      European Union based upon whether they feed endogenously off the yolk or
      exogenously by procurement and ingestion of food. The concept of saltatory
      ontogeny suggests development is not gradual but proceeds in leaps separated by a
      series of stable developmental states. In this context, endogenous/exogenous
      feeding also distinguishes the developmental phases of embryo (egg),
      eleutheroembryo (feeding off the yolk sac) and larvae (exogenous feeding) in
      fish. The recent proposal for the Fish Embryo Test (FET) as an animal alternative
      to the standard fish acute toxicity test (OECD 203 and equivalent tests) puts a
      clear focus on the need to identify the non-protected and protected life
      intervals in test species as well as their sensitivities which coincides with the
      developmental phases identified in saltatory ontogeny. In this paper we described
      a method to quantify embryo, eleutheroembryo, and larva phases in Danio rerio,
      the zebrafish. Danio eleutheroembryos preyed upon 5 different protozoan species
      (Euglena, Euplotes, Paramecium aurelia, Paramecium bursaria and Paramecium
      multimicronucleatum) between 24 and 48hr following hatching (85-95% of fish, n=20
      per species, 25 degrees C). Based upon these data it is recommended that testing
      of developing zebrafish embryos should be terminated between 24 and 48hr after
      hatching in order to be compliant with existing animal welfare legislation within
      Europe.

PMID- 20042244
TI  - Dementia care costs and the patient's quality of life (QoL) in Taiwan: home
      versus institutional care services.
AB  - Organizing optimal care for demented older people is a complex health care issue.
      Controversies of service models for demented patients should be balanced between
      cost of care, placement, and quality of life (QoL). The main purpose of this
      study was to explore the optimal model of dementia care in Taiwan by evaluating
      the care cost, patients' QoL and healthcare settings. Overall, 140 pairs of
      demented patients and their primary informal caregivers were enrolled (89
      community-living and 51 institute-living). Compared to institute-living subjects,
      community-living subjects were significantly better in cognition, physical
      function and QoL. The annual direct cost of institutional care was significantly
      higher than community care (464,193 New Taiwanese Dollar (NTD) vs. 144,047 (NTD),
      p<0.001), but indirect cost was significantly higher in home care (287,904 NTD
      vs. 35,665 NTD, p<0.001). The care cost of home care subjects with low physical
      dependence was significantly lower than institutional care subjects, but the care
      cost of home care subjects with high physical dependence was significantly higher
      than institutional care subjects. Physical dependence was the significant
      determinant of QoL for demented patients in this study. In conclusion, demented
      patients with low physical dependence may be cared in the communities with
      support and those who had high physical dependence may be cared in the institutes
      in terms of the balance of QoL and the care cost.

PMID- 20042245
TI  - Obesity and depressive symptoms in elderly Koreans: evidence for the "Jolly Fat"
      hypothesis from the Ansan Geriatric (AGE) Study.
AB  - The current study is to examine the association between obesity and depressive
      symptoms and to test the validity of "Jolly Fat" hypothesis in elderly Koreans. A
      total of 1229 elderly (60-85 years old) Koreans selected from the Ansan Geriatric
      Study participated in this study. Body mass index (BMI) was calculated from the
      measured weights and heights of subjects. Overweight and obese were defined as
      BMI > or =23 and > or =25, respectively. Depressive symptoms were measured using
      the 30-item Korean version of the Geriatric Depression Scale (K-GDS), with a
      cutoff point of 18. The prevalence of depressive symptoms in elderly Korean women
      was higher than in men (20.9% vs. 9.2%, p<0.001). Among elderly women, higher
      mean values of obesity indexes, such as weight, BMI, waist circumference, waist
      hip ratio, and body fat mass, were found in normal subjects than in those with
      depressive symptoms. No such differences were found in elderly men. Obese elderly
      women were less likely to suffer from depressive symptoms compared to those with
      apparently normal weight (odds ratio (OR)=0.63, 95% CI: 0.41-0.96). This inverse
      association was evident after adjustment for confounders, such as age, education,
      personal expenses, smoking, alcohol consumption, regular exercise, self-perceived
      health, presence of chronic disease, and cognitive function. Our data are
      consistent with the "Jolly Fat" hypothesis being valid only in women, but not in
      men, among elderly Koreans. A causal relationship between obesity and depressive
      symptoms should be evaluated in future studies in elderly Korean women.

PMID- 20042246
TI  - T-wave inversion after a severe head injury without ischemic heart disease.
AB  - Electrocardiographic changes mimicking an acute coronary event with T-wave
      inversion have been reported in the resting electrocardiogram in patients without
      ischemic heart disease but with acute ischemic stroke, or subarachnoid
      hemorrhage, or intracerebral hemorrhage, or a severe head injury. We present a
      case of T-wave inversion in a 73-year-old Italian woman admitted to the Emergency
      Department following a severe head injury. Pericarditis, pericardial effusion,
      and acute coronary event were excluded. Ischemic stroke, subarachnoid hemorrhage,
      and intracerebral hemorrhage were also excluded. Also this case focuses attention
      on T-wave inversion after a severe head injury without ischemic heart disease.

PMID- 20042247
TI  - Relationship between smaller calcifications and lipid-rich plaques on integrated
      backscatter-intravascular ultrasound.
AB  - We evaluated the relationship between coronary calcification and plaque
      characteristics using integrated backscatter-intravascular ultrasound (IB-IVUS),
      focusing on spotty calcification. Seventy-two patients with culprit plaques
      containing spotty calcification were evaluated. The average degree of all the
      spotty calcifications (averaged arc) negatively correlated with the % lipid
      volume (LV) on IB-IVUS. Multivariate analysis showed the averaged arc was an
      independent predictor of % LV. Our observations suggest that smaller plaque
      calcifications are associated with lipid-rich characteristics in patients with a
      spotty calcification pattern.

PMID- 20042248
TI  - Engineering strategies to emulate the stem cell niche.
AB  - The stem cell niche is an anatomical site that contains a reservoir of
      multipotent stem cells (SCs) that can maintain normal tissue, or replenish
      injured or aged cell populations, in response to mechanisms that regulate whether
      they should remain quiescent, undergo self-renewal, or differentiate. The choice
      among these hallmark SC behaviors is governed by intricate soluble and "solid
      phase" signals that are systemic or presented by the local niche cells. In this
      review, we discuss the progress achieved in understanding the mechanisms and
      principles that govern microenvironmental regulation of SC behavior, and focus on
      novel approaches that have been developed to synthesize this basic information to
      engineer creative strategies for harnessing and controlling SCs ex vivo and in
      vivo.

PMID- 20042249
TI  - The relationship between membrane damage, release of protein and loss of
      viability in Escherichia coli exposed to high hydrostatic pressure.
AB  - The aim of this work was to examine a possible association between resistance of
      two Escherichia coli strains to high hydrostatic pressure and the susceptibility
      of their cell membranes to pressure-induced damage. Cells were exposed to
      pressures between 100 and 700 MPa at room temperature (approximately 20 degrees
      C) in phosphate-buffered-saline. In the more pressure-sensitive strain E. coli
      8164, loss of viability occurred at pressures between 100 MPa and 300 MPa and
      coincided with irreversible loss of membrane integrity as indicated by uptake of
      propidium iodide (PI) and leakage of protein of molecular mass between 9 and 78
      kDa from the cells. Protein release increased to a maximum at 400 MPa then
      decreased, possibly due to intracellular aggregation at the higher pressures. In
      the pressure-resistant strain E. coli J1, PI was taken up during pressure
      treatment but not after decompression indicating that cells were able to reseal
      their membranes. Loss of viability in strain J1 coincided with the transient loss
      of membrane integrity between approximately 200 MPa and 600 MPa. In E. coli J1
      leakage of protein occurred before loss of viability and the released protein was
      of low molecular mass, between 8 and 11 kDa and may have been of periplasmic
      origin. In these two strains differences in pressure resistance appeared to be
      related to differences in the ability of their membranes to withstand disruption
      by pressure. However it appears that transient loss of membrane integrity during
      pressure can lead to cell death irrespective of whether cells can reseal their
      membranes afterwards.

PMID- 20042250
TI  - Operator-splitting-based reactive transport models in strong feedback of porosity
      change: The contribution of analytical solutions for accuracy validation and
      estimator improvement.
AB  - Reactive transport is a highly non-linear problem requiring the most efficient
      algorithms to rapidly reach an accurate solution. The non-linearities are
      increased and the resolution is even more demanding and CPU-intensive when
      considering feedback of dissolution or precipitation reactions on hydrodynamic
      flow and transport, commonly referred to as the variable porosity case. This is
      particularly true near clogging, which leads to very stiff systems and therefore
      small time-steps. The operator-splitting approach often cited is a widely use
      method to solve these problems: it consists in solving sequentially the transport
      then the chemistry part of the problem. Operator-splitting appears to be an
      accurate approach, provided that the solution is iteratively improved at each
      time-step. The paper details analytical solutions and test-cases for this class
      of problems. They demonstrate that iterative improvement is then compulsory. They
      also helped develop an improved estimator/corrector method which allows to reach
      convergence faster and to reduce stiffness. The efficiency improvement is
      significant as illustrated by an example of carbonation of a cement paste, a well
      known problem that leads to complete clogging of the interface layer.

PMID- 20042251
TI  - Enzymatic glycosylation, inhibitor design, and synthesis and formation of glyco
      self assembled monolayers for simulation of recognition.
AB  - Glycosyltransferases from the albumen gland of Helix pomatia could be used in
      tandem mode for the chemoenzymatic synthesis of beta,1-3/beta,1-6-linked
      oligogalactans. By employing recombinant trans-sialidase of Trypanosoma cruzi
      (TcTS) the formation of a range of modified Galbeta,1-3GalNAc derivatives could
      be terminally alpha,2-3 sialylated. Biacore studies indicated the binding of
      these modified trisaccharides to myelin-associated glycoprotein (MAG). Using an
      eight-step synthetic route N-acyl-modified sialyl donor structures could be
      obtained. TcTS was used to transfer these structures to an isolactoside, and
      Michaelis constants of the donors indicated the kind and size of modifications
      allowed at the 5-nitrogen site. A number of sialic acid C-glycosides could be
      obtained via the C-allyl sialoside and subsequent metathesis. Biacore
      measurements showed derivatives substituted with aromatic residues to give K(D)
      values in the mM range. Benzaldehyde-functionalized glycosides of mono and
      disaccharides were synthesized by metathesis and could be used for the formation
      of novel glyco-self assembled monolayers (glyco-SAMs) employing various tether
      structures and attached to gold surfaces. Initial experiments were performed with
      concanavalin A and manno-SAMs. By atomic force microscopic measurements of
      tethered glycosides attached to gold-coated tips and surfaces weak forces in the
      nN range could be detected. Structure activity correlation of forces suggested
      rationales for complex interactions of various glycosides including minor
      stereochemical variations.

PMID- 20042252
TI  - Cloning and molecular characterization of the potato RING finger protein gene
      StRFP1 and its function in potato broad-spectrum resistance against Phytophthora
      infestans.
AB  - Really interesting new gene (RING) finger proteins function as ubiquitin ligase
      and play key roles in biotic and abiotic stresses. A new RING-H2 finger protein
      gene, StRFP1, was cloned from Phytophthora infestans-inoculated leaves of potato
      (Solanum tuberosum) clone 386209.10, which is free of R1-R11 genes. The deduced
      amino acid sequence was characterized by an N-terminal transmembrane domain, a
      GLD region and a RING-H2 finger signature. StRFP1 is homologous to the tobacco
      NtACRE132 protein and belongs to the ATL family. The DNA gel blot analysis and
      mapping revealed that StRFP1, an intron-free gene, had one to two copies in the
      potato genome and was located on chromosome 3. RT-PCR assays showed that StRFP1
      was constitutively expressed in potato plants and significantly induced in
      detached potato leaves by P. infestans and plant defense-related signal
      molecules, abscisic acid, salicylic acid and methyl jasmonate. Transient
      expression studies revealed that StRFP1 fused with GFP localized to the plasma
      membrane or out of that in onion epidermal cells. The function of StRFP1 in
      potato resistance against late blight was further investigated by constructing
      overexpression and RNA interference (RNAi) vectors, which were introduced into
      potato cv. E-potato 3, respectively. By challenging the detached leaves with
      mixture races of P. infestans, all of the StRFP1-overexpressing plants displayed
      slower disease development than non-transformed controls in terms of the lesion
      growth rate (LGR). In contrast, StRFP1-silencing plants through RNAi were more
      susceptible to pathogen infection. The present results demonstrate that StRFP1
      contributes to broad-spectrum resistance against P. infestans in potato.

PMID- 20042253
TI  - Nosocomial infections caused by community-associated methicillin-resistant
      Staphylococcus aureus in Colombia.
AB  - BACKGROUND: Community-associated methicillin-resistant Staphylococcus aureus
      strains (CA-MRSA) have emerged as the causative agent of health care-associated
      infections. METHODS: An observational and prospective study was carried out in 5
      hospitals in Bogota, Colombia; severe MRSA infections were identified, and their
      origin led to classification as health care-associated (HA-MRSA), community
      associated, or nosocomial infections. MRSA isolates were analyzed by SCCmec,
      pulsed-field gel electrophoresis, multilocus sequence typing, and virulence
      factors. RESULTS: Twenty-six (10.4%) CA-MRSA nosocomial infection-causing strains
      (eg, USA300) were detected in 250 MRSA infection isolates in mainly primary
      bacteremia and surgical site infections. The mortality related to nosocomial
      infection by CA-MRSA was 27%. CONCLUSION: The presence of nosocomial infection by
      CA-MRSA in Colombia was confirmed.

PMID- 20042254
TI  - Raised emotions: A critique of the Peshkin Approach to Reflection.
AB  - AIMS AND OBJECTIVES: We critique a new approach to reflection in nursing that
      uses thoughts and feelings as the focus of the reflective process. BACKGROUND: We
      have developed the 'Peshkin Approach to Reflection'; so-called because it is
      influenced by the work of Peshkin and his focus on the 'subjective I'. Whereas
      most reflective models used in nursing take an incident as the starting point,
      this new approach focuses on subjective feelings and thoughts. DISCUSSION: We
      offer an overview of the stages of the process: preparation; writing, analysis,
      and application to practice. Central to the paper is a critique of the approach
      with particular emphasis on the issues raised by focusing on emotions as part of
      the reflective process. We show that within the emotional labour of nursing,
      feelings may become repressed. Thus, we suggest that bringing emotions to the
      forefront of reflective practice in an appropriately supportive environment has
      significant benefits. CONCLUSIONS: Emotions are inextricably bound with nursing
      practice. For that reason, we argue that much can be gained from raising emotions
      in a manner that helps nursing students - or indeed nurses and other
      practitioners - gain a deeper self-understanding. In turn, this can enhance
      therapeutic use of self.

PMID- 20042255
TI  - Comparison of methods to assess body fat in non-obese six to seven-year-old
      children.
AB  - BACKGROUND & AIM: Different non-invasive methods exist to evaluate total body fat
      in children. Most methods have shown to be able to confirm a high fat percentage
      in children with overweight and obesity. No data are available on the estimation
      of total body fat in non-obese children. The aim of this study is to compare
      total body fat, assessed by different methods in non-obese children. METHODS: We
      compared total body fat, assessed by isotope dilution, dual energy X-ray,
      skinfold thickness, bioelectrical impedance analysis, combination of these
      methods as well as BMI in 30 six to seven-year-old children. RESULTS: The
      children had a mean BMI of 16.01kg/m(2) (range 13.51-20.32) and five children
      were overweight according to international criteria. Different methods showed
      rather different absolute values for total body fat. Bland-Altman analysis showed
      that the difference between the DEXA method and isotope dilution was dependent on
      the fat percentage. Children with the same BMI show a marked variation in total
      body fat ranging from 8% to 22% as estimated from the isotope dilution method.
      CONCLUSION: Non-invasive methods are presently not suited to assess the absolute
      amount of total body fat in 6-7 years old children.

PMID- 20042256
TI  - A randomized, parallel, open-label study to compare once-daily sevelamer
      carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing
      in CKD patients on hemodialysis.
AB  - BACKGROUND: Sevelamer carbonate powder for oral suspension is a new dosage form
      of sevelamer, which may be suited to once-daily dosing. STUDY DESIGN: Randomized
      parallel open-label study. SETTING & PARTICIPANTS: Hemodialysis patients.
      INTERVENTION: After a 2-week phosphate-binder washout, patients were randomly
      assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer
      hydrochloride tablets. OUTCOMES: Assessment of noninferiority with respect to
      change from baseline in serum phosphorus levels. MEASUREMENTS: Serum phosphorus
      to 24 weeks. RESULTS: After washout, mean serum phosphorus level decreased 2.0 +/
      1.8 mg/dL (from 7.3 +/- 1.3 mg/dL) for sevelamer carbonate and 2.9 +/- 1.3 mg/dL
      (from 7.6 +/- 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper
      CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of
      sevelamer carbonate powder-treated patients and 64% of sevelamer hydrochloride
      tablet-treated patients had serum phosphorus levels within the National Kidney
      Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (> or =3.5
      and < or =5.5 mg/dL). Overall, the percentage of patients with treatment-emergent
      adverse events was similar between groups. However, a greater percentage of
      treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and
      vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In
      addition, 4 (3%) sevelamer carbonate-treated patients experienced stimulation of
      the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer
      carbonate powder. A greater percentage of sevelamer carbonate powder-treated
      patients discontinued treatment because of these treatment-related events or
      consent withdrawal. LIMITATIONS: Study was not blinded. Once-daily dose may not
      have been with the highest phosphate content meal; further exploration of
      alternative dosing schemes is warranted. CONCLUSIONS: Once-daily administration
      of sevelamer carbonate powder was not as effective in decreasing serum phosphorus
      levels as thrice-daily administration of sevelamer hydrochloride tablets.
      Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus
      levels significantly, reaching the KDOQI phosphorus target in most patients.
      Therefore, once-daily dosing of sevelamer carbonate may be a reasonable
      alternative.

PMID- 20042257
TI  - Toxic nephropathies: core curriculum 2010.

PMID- 20042259
TI  - Kidney function and rate of bone loss at the hip and spine: the Canadian
      Multicentre Osteoporosis Study.
AB  - BACKGROUND: The relationship between kidney function and bone loss is unclear.
      STUDY DESIGN: A prospective observational study. SETTING & PARTICIPANTS: 191 men
      and 444 women aged > or = 50 years participating in a population-based
      observational study designed to determine risk factors for bone loss and
      fractures. PREDICTORS: The primary predictor of change in bone mineral density
      (BMD) was estimated creatinine clearance (using the Cockcroft-Gault formula)
      measured at baseline and stratified by quartiles. Our secondary predictor was
      estimated glomerular filtration rate using the Modification of Diet in Renal
      Disease Study equation, also stratified by quartiles. OUTCOMES & MEASUREMENTS:
      Changes in BMD at the lumbar spine, total hip, and femoral neck during 5 years.
      RESULTS: Compared with participants in the first quartile of estimated creatinine
      clearance (>101.2 mL/min), those in remaining quartiles were older (quartile 1,
      50.0 years; quartile 2 [101.2-83.4 mL/min], 54.7 years; quartile 3 [83.4-68.3
      mL/min], 60.5 years; and quartile 4 [<68.3 mL/min], 68.3 years); weighed less;
      reported more sedentary hours; were less likely to report excellent, very good,
      or good self-reported health; consumed less caffeine; and had lower serum calcium
      and phosphate and higher serum parathyroid hormone levels. After adjusting for
      age, weight, sex, baseline BMD, and these differences, compared with those in the
      first quartile, those in the fourth quartile had decreases in BMD of 0.08 g/cm(2)
      (95% CI, 0.04-0.1) at the lumbar spine, 0.08 g/cm(2) (95% CI, 0.06-0.1) at the
      femoral neck, and 0.09 g/cm(2) (95% CI, 0.07-0.1) at the total hip. Bone loss did
      not increase with worsening kidney function (P for trend > 0.05). Results were
      not substantially different using estimated glomerular filtration rate.
      LIMITATIONS: Observational study design and indirect measures of kidney function.
      CONCLUSIONS: Men and women with impaired kidney function are at increased risk of
      bone loss, even with minimal reduction in kidney function.

PMID- 20042260
TI  - Fluid overload and mortality in children receiving continuous renal replacement
      therapy: the prospective pediatric continuous renal replacement therapy registry.
AB  - BACKGROUND: Critically ill children with hemodynamic instability and acute kidney
      injury often develop fluid overload. Continuous renal replacement therapy (CRRT)
      has emerged as a favored modality in the management of such children. This study
      investigated the association between fluid overload and mortality in children
      receiving CRRT. STUDY DESIGN: Prospective observational study. SETTING &
      PARTICIPANTS: 297 children from 13 centers across the United States participating
      in the Prospective Pediatric CRRT Registry. PREDICTOR: Fluid overload from
      intensive care unit (ICU) admission to CRRT initiation, defined as a percentage
      equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%. OUTCOME &
      MEASUREMENTS: The primary outcome was survival to pediatric ICU discharge. Data
      were collected regarding demographics, CRRT parameters, underlying disease
      process, and severity of illness. RESULTS: 153 patients (51.5%) developed < 10%
      fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93
      patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or
      = 20% fluid overload at CRRT initiation had significantly higher mortality
      (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those
      with < 10% fluid overload (45/153; 29.4%). The association between degree of
      fluid overload and mortality remained after adjusting for intergroup differences
      and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05),
      suggesting a 3% increase in mortality for each 1% increase in severity of fluid
      overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients
      with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8
      25.7). LIMITATIONS: This was an observational study; interventions were not
      standardized. The relationship between fluid overload and mortality remains an
      association without definitive evidence of causality. CONCLUSIONS: Critically ill
      children who develop greater fluid overload before initiation of CRRT experience
      higher mortality than those with less fluid overload. Further goal-directed
      research is required to accurately define optimal fluid overload thresholds for
      initiation of CRRT.

PMID- 20042258
TI  - The management of diabetic neuropathy in CKD.

PMID- 20042261
TI  - Is presence of ANCA in crescentic IgA nephropathy a coincidence or novel clinical
      entity? A case series.
AB  - BACKGROUND: There are few anecdotal reports of circulating antineutrophil
      cytoplasmic autoantibodies (ANCAs) in patients with immunoglobulin A (IgA)
      nephropathy. STUDY DESIGN: Retrospective case series. SETTING & PARTICIPANTS: We
      studied 8 patients with crescentic IgA nephropathy associated with ANCAs against
      myeloperoxidase (n = 5) and proteinase 3 (n = 3) followed up for 2.4 +/- 1.7
      years. They were compared with 26 patients with IgA nephropathy with > 10%
      crescentic glomeruli, but negative for ANCAs. OUTCOMES: We analyzed clinical and
      histologic features of patients and their response to treatment. MEASUREMENTS:
      Screening for ANCAs was performed using indirect immunofluorescence, and positive
      results were verified using enzyme-linked immunosorbent assay. RESULTS: All
      patients with crescentic IgA nephropathy and positive for ANCAs, compared with
      only one-third of ANCA-negative patients, presented with the clinical syndrome of
      rapid progressive glomerulonephritis. ANCA-positive patients reached a higher
      peak serum creatinine level within the first 3 months (4.2 +/- 2.2 vs 2.5 +/- 1.9
      mg/dL; estimated glomerular filtration rate, 19.3 +/- 10.2 vs 45.9 +/- 30.1
      mL/min/1.73 m(2)). ANCA-positive patients with IgA nephropathy had a higher
      percentage of crescentic glomeruli (54.3% +/- 18%) compared with ANCA-negative
      patients with crescentic IgA nephropathy (34.5% +/- 26%). ANCA-positive patients
      were treated using cyclophosphamide and corticosteroids. Kidney function improved
      in all these patients: serum creatinine level decreased from the peak of 4.2 +/-
      2.2 to 1.7 +/- 0.7 mg/dL at the end of follow up (estimated glomerular filtration
      rate, 19.3 +/- 10.2 to 44.6 +/- 11.1 mL/min/1.73 m(2)). In contrast, no
      significant improvement was achieved in ANCA-negative patients. CONCLUSION:
      Patients with IgA nephropathy, crescents, and positive for ANCAs represent a
      clinical entity with a diverse more exaggerated clinical and histologic picture.
      However, disease in these patients responded well to aggressive immunosuppressive
      therapy.

PMID- 20042262
TI  - Patients' narrative accounts of open-heart surgery and recovery: authorial voice
      of technology.
AB  - In this narrative inquiry, we examined patients' experiential accounts of
      technology in open-heart surgery and recovery. A convenience sample of sixteen
      individuals was recruited from a preoperative clinic at a regional centre for
      cardiac services in Canada. Each participated in two interviews following
      transfer from cardiovascular intensive care and 4-6 weeks post discharge from the
      hospital. Participants also documented their experiences in journals during the
      first 3-4 weeks following discharge. The focal point of the study's theoretical
      foundations was narrative emplotment, which directs attention to the active
      processes of plot construction and shaping forces of stories. In our narrative
      analysis, we used narrative mapping to document the temporal flow of events. We
      found that technology acted as the authorial voice, or controlling influence,
      over how participants' narratives were shaped and unfolded. Key were the ways in
      which technology as the authorial voice was linked with participants becoming
      background characters and surrendering agency. Problematic and important to
      health care professionals is ensuring that authorial voice shifts back to
      patients so that they become active in shaping their own course of recovery. This
      study underscores the benefits of using literary techniques such as narrative
      analysis in health science research. Examining the narrative structures and
      forces that shape patients' stories sheds light on how health care professionals
      and their technologically-driven practices of care strongly affect the stories'
      content and how they unfold. By focusing on how stories unfolded, we revealed
      ways in which cardiac surgery practices and patients' course of recovery could be
      enhanced.

PMID- 20042263
TI  - Macrosomia is the only reliable predictor of shoulder dystocia in babies weighing
      3.5 kg or more.
AB  - OBJECTIVE: To determine if shoulder dystocia can be predicted in babies born
      weighing 3.5 kg or more. STUDY DESIGN: A case-control study nested in a perinatal
      database of 899 mothers and their babies who weighed 3.5 kg or more. All were
      term pregnancies and delivered vaginally. A case was defined as any baby that
      encountered shoulder dystocia at delivery. Controls were deliveries over the same
      period that were not complicated by shoulder dystocia. A logistic regression
      model was created with macrosomia, parity, previous delivery of more than 3.5 kg,
      diabetes in pregnancy, prolonged labor, prolonged second stage and instrumental
      delivery as the independent variables. The adjusted odds ratio and the receiver
      operator characteristics (ROC) curves were used to see if these variables, both
      individually and as a model, were associated with or were discriminative enough
      to predict shoulder dystocia; an ROC curve of more than 0.7 showing good
      prediction. RESULTS: There were 36 cases of shoulder dystocia during the study
      period, an incidence of 4%. Previous delivery of more than 3.5 kg, prolonged
      labor and prolonged second stage were not associated with shoulder dystocia.
      Although diabetes and instrumental delivery were independently and significantly
      associated with shoulder dystocia their importance as a predictor became relevant
      only in the presence of macrosomia. CONCLUSION: Macrosomia is the only reliable
      predictor of shoulder dystocia.

PMID- 20042264
TI  - Expression of the imprinted IGF2 and H19 genes in the endometrium of cases with
      unexplained infertility.
AB  - OBJECTIVE: As genomic imprinting plays a critical role in the development of the
      placenta, the aim of this study was to detect whether the expression levels of
      the imprinted genes IGF2 and H19 in the endometrium differ between infertile and
      fertile women. STUDY DESIGN: Total RNA was extracted from 30 (15 unexplained
      infertile and 15 fertile) women's endometrial tissue. cDNA was synthesized from
      total RNAs of each sample. IGF2 and H19 mRNA expression levels were measured
      quantitatively using the Real Time PCR method. In order to determine the allelic
      expression of IGF2 and H19, genomic DNA was extracted from endometrial tissues.
      RESULTS: When compared with the control group, increased mRNA expression of IGF2
      was detected (1.5-fold change, P=0.015) in the unexplained infertility group. In
      contrast, H19 expression was lower in the infertility group as compared to the
      control group (4-fold change, P<0.0001). Restriction analysis of cDNA-derived PCR
      product showed that all patients and controls indicated monoallelic expression of
      IGF2 and H19. CONCLUSION: Our results showed that altered expression of these
      imprinted genes might affect implantation and that their timely and appropriate
      activation is important for proper functioning. To understand the molecular
      epigenetic basis of implantation and placental development, genomic imprinted
      genes should be further investigated.

PMID- 20042265
TI  - Guidelines for the management of ovarian cancer during pregnancy.
AB  - Adnexal masses may be detected during prenatal ultrasound, and ovarian cancer may
      be suspected during pregnancy. Even though such masses are rarely malignant
      (1/10,000 to 1/50,000 pregnancies), the possibility of borderline tumour or
      cancer must be considered. It is a common assumption by both patients and
      physicians that if an ovarian cancer is diagnosed during pregnancy, treatment
      necessitates sacrificing the well-being of the fetus. However, in most cases, it
      is possible to offer appropriate treatment to the mother without placing the
      fetus at serious risk. The care of a pregnant woman with cancer involves
      evaluation of sometimes competing maternal and fetal risks and benefits. These
      recommendations attempt to balance these risks and benefits; however, they should
      be considered advisory and should not replace specific interdisciplinary
      consultation with specialists in maternal-fetal medicine, gynecologic oncology
      and pediatrics, as well as imaging and pathology, as needed. Second level
      ultrasound including Doppler is needed. MRI is not often necessary, and CA 125 is
      of low contribution. We suggest surgery be performed after 15 weeks gestation for
      ovarian masses which (1) persist into the second trimester, (2) are greater than
      5-10 cm in diameter, or (3) have solid or mixed solid and cystic ultrasound
      characteristics. During the antepartum period surgical staging and debulking,
      unilateral salpingo-oophorectomy on the side with the tumour, peritoneal cytology
      and exploration are necessary. Women found to have advanced stage epithelial
      ovarian cancer should consider having completion of the debulking of the
      reproductive organs at the conclusion of the pregnancy. If chemotherapy is
      indicated, we recommend delaying administration, if possible, until after the
      delivery or at least after 20 weeks in order to minimize the potential fetal
      toxicity.

PMID- 20042266
TI  - Adsorption of hexavalent chromium from aqueous medium onto carbonaceous
      adsorbents prepared from waste biomass.
AB  - This paper reports the adsorption of Cr(VI) ions from aqueous solution by
      sulphuric acid treated sunflower waste. Two adsorbents, namely SHC and SSC, were
      prepared from sunflower plant head and stem waste. The adsorbents were
      characterized by FT-IR, SEM and EDX. The surface areas of SHC and SSC were 1.17
      and 1.28 m(2)g(-1), respectively. The effect of various process parameters namely
      pH, temperature, initial metal ion concentration, adsorbent dosage and contact
      time has been studied. The optimum conditions for removal of Cr (VI) were found
      to be pH=2, contact time=2h, adsorbent dosage=4.0 g/L, concentration=250 mg/L,
      temperature=25+/-1 degrees C, rpm=180. The percent removal at these optimum
      conditions was found to be 75.7% and 85.4% for SHC and SSC respectively. The
      Freundlich, Langmuir and D-R models were applied for mathematical description of
      adsorption equilibrium. Adsorption data were well described by the Langmuir
      isotherm with maximum adsorption capacities of 53.76 mg/g and 56.49 mg/g for SHC
      and SSC, respectively. Overall, the experimental results suggest that SHC and SSC
      could be used as low cost alternative adsorbents for the treatment of Cr(VI)
      containing wastewater. A comparison of different kinetic models showed that our
      data fitted well to the pseudo-second order model.

PMID- 20042267
TI  - Electrocoagulation of blue reactive, red disperse and mixed dyes, and application
      in treating textile effluent.
AB  - This study investigated the efficiency of electrocoagulation in removing color
      from synthetic and real textile wastewater. Two representative dye molecules were
      selected for the synthetic dye wastewater: a blue reactive dye (Reactive Blue
      140) and a disperse dye (Disperse Red 1). The electrochemical technique showed
      satisfactory color removal efficiency and reliable performance in treating both
      individual and mixed dye types. The removal efficiency and energy consumption
      data showed that, for a given current density, iron was superior to aluminum in
      treating both the reactive dye and the disperse dye. With an initial dye
      concentration of 100 mg L(-1), the energy cost in achieving >95% color removal
      was on the order of 1 kWh m(-3) for both dyes. The effect of changing the initial
      pH of the samples on the removal efficiency and energy consumption was also
      studied. It was found that the design parameters used for the synthetic
      wastewater were less effective for treatment of real textile wastewater, with 1
      in 5 tests on real wastewater failing.

PMID- 20042268
TI  - Assessing relationships among life-cycle environmental impacts with dimension
      reduction techniques.
AB  - Nowadays, there is a trend in many countries towards more environmentally benign
      products and processes. Life-Cycle Assessment (LCA) is a quantitative analysis
      tool developed and utilized for the evaluation of environmental impacts occurring
      throughout the entire life-cycle of a product, process or activity. LCA requires
      a large amount of data in its different phases and can also generate large
      amounts of results which may be hard to interpret. In order to uncover and
      visualize the structure of large multidimensional data sets, Multivariate
      Analysis techniques can help. Hence, in this paper, a methodology using Principal
      Component Analysis and Multi-Dimensional Scaling is proposed and illustrated by
      means of two case studies. The first case study evaluates the operation of
      several wastewater treatment plants. The second case study deals with the
      environmental evaluation of the cultivation, processing and consumption of
      mussels. In both case studies, the redundancy present in the data allowed a
      dimensionality reduction from seven and ten to two dimensions, with a small loss
      of information. Plotting the environmental impact data in these two dimensions
      can help visualize, interpret and communicate them.

PMID- 20042269
TI  - Workload of the emergency room neurologists and the neurological inpatient
      department in a Greek tertiary care hospital.
AB  - BACKGROUND: Data concerning the number of patients presenting to the emergency
      room (ER) and the workload in the departments in the European Union countries are
      scarce. In contrast to most European practice, Greek public hospitals in cities
      with more than one public health facilities are on-call not on a daily, but on a
      rotational basis. Exact data from Greece on the number of patients referred to
      the ER or the number of patients admitted to regular inpatient departments of the
      public hospitals under these conditions is lacking. PATIENTS AND METHODS: From
      February 1st, 2006 to January 31st, 2007, we performed an open prospective study
      on the workload at the ER as well as the inpatient department of the Neurological
      Clinic of Papageorgiou General Hospital in Thessaloniki, Greece. In addition, we
      performed an analysis of the number of inpatient admission to the Department of
      Neurology per trimester from January 1st, 2002 until March 31st, 2008. RESULTS:
      During the study period, a total of 5901 patients required neurological
      examination in the ER (8.75% of all ER patients). In parallel, 2054 patients were
      admitted to the neurological ward for hospitalization exceeding 24h with a mean
      hospitalization of 3.95 days. CONCLUSION: These data suggest that the workload of
      a tertiary care neurological in- and outpatient department is large. More
      research is needed to determine the impact this has on patient outcomes.

PMID- 20042270
TI  - Effect of anticoagulant and antiplatelet therapy in patients with spontaneous
      intra-cerebral hemorrhage: Does medication use predict worse outcome?
AB  - OBJECTIVES: To assess the impact of anticoagulants and antiplatelet agents on the
      severity and outcome of spontaneous non-traumatic intra-cerebral hemorrhage
      (ICH). To evaluate associations between reversal of anticoagulation and
      mortality/morbidity in these patients. METHODS: Data was collected on a
      consecutive cohort of adults presenting with ICH to an academic Emergency
      Department over a 3-year period starting January 2006. RESULTS: The final cohort
      of 245 patients consisted of 125 females (51.1%). The median age of the cohort
      was 73 years [inter-quartile (IQR) range of 59-82 years]. Antiplatelet (AP) use
      was seen in 32.6%, 18.4% were using anticoagulant (AC) and 8.9% patients were on
      both drugs (AC+AP). Patients on AC had significantly higher INR (median 2.3) and
      aPTT (median 31 s) when compared to patients not on AP/AC (median INR 1.0, median
      aPTT 24s; p<0.001). Similarly patients on AC+AP also had higher INR (median 1.9)
      and aPTT (median 30s) when compared to those not on AC/AP (p<0.001). Hemorrhage
      volumes were significantly higher for patients on AC alone (median 64.7 cm(3))
      when compared to those not on either AC/AP (median 27.2 cm(3); p=0.05). The same
      was not found for patients using AP (median volume 20.5 cm(3); p=0.813), or both
      AC+AP (median volume 27.7 cm(3); p=0.619). Patients on AC were 1.43 times higher
      at risk to have intra-ventricular extension of hemorrhage (IVE) as compared to
      patients not on AC/AP (95% CI 1.04-1.98; p=0.035). There was no relationship
      between the use of AC/AP/AC+AP and functional outcome of patients. Patients on AC
      were 1.74 times more likely to die within 7 days (95% CI 1.0-3.03; p=0.05). No
      relationship was found between use of AP or AC+AP use and mortality. Of the 82
      patients with INR>1.0, 52 patients were given reversal (minimum INR 1.4, median
      2.3). Therapy was heterogeneous, with fresh frozen plasma (FFP) being the most
      commonly used agent (86.5% patients, median dose 4U). Vitamin K, activated factor
      VIIa and platelets were the other agents used. Post reversal, INR normalized
      within 24h (median 1.2, IQR 1.1-1.3). There was no association between reversal
      and volume of hemorrhage, IVE, early mortality (death<7 days) or functional
      outcome. CONCLUSIONS: Anticoagulated patients were at 1.7 times higher risk of
      early mortality after ICH. Reversal of INR to normal did not influence mortality
      or functional outcome.

PMID- 20042271
TI  - Targeting aminopeptidase N (APN/CD13) with cyclic-imide peptidomimetics
      derivative CIP-13F inhibits the growth of human ovarian carcinoma cells.
AB  - Aminopeptidase N (APN/CD13) is an essential peptidase involved in the process of
      tumor growth, metastasis and angiogenesis. Inhibition of APN/CD13 may be an
      effective strategy for cancer treatment. CIP-13F is a cyclic-imide
      peptidomimetics compound designed to fit the active pockets S1 and S'1 of
      APN/CD13 that act in tumor proliferation. Our aim in this study was to evaluate
      the efficacy of CIP-13F as a candidate compound for cancer treatment. The
      experiments were performed on the human ovarian carcinoma (OVCA) ES-2 and HRA
      cell lines, which have high and low levels of APN/CD13 respectively. CIP-13F
      significantly blocked APN/CD13 activity on the surface of ES-2 cells as measured
      by quantitating the enzymatic cleavage of the substrate l-leucine-p-nitroanilide.
      CIP-13F effectively inhibited ES-2 cell growth and migration without significant
      cytotoxic effect. In contrast, CIP-13F did not significantly inhibit HRA cell
      growth, indicating that CIP-13F may inhibit ES-2 cell growth via suppression of
      APN/CD13. The suppression of APN/CD13 was also observed by using the assays of
      flow cytometry and Western blot analysis. Further, the inhibitory effects of CIP
      13F on APN/CD13 and on ES-2 proliferation were supported by the induction of ES-2
      apoptosis. CIP-13F-treated ES-2 cells resulted apoptotic characteristics, such as
      induction of externalization of phosphatidylserine and DNA laddering fragment.
      The activation of caspase-3 and poly ADP-ribose polymerase (PARP) was also
      enhanced. The inhibitory effects of CIP-13F on APN/CD13 expression and on ES-2
      proliferation were confirmed in mice bearing ES-2 xenografts. CIP-13F delayed the
      growth of ES-2 xenografts in mice after 2 weeks of vena caudalis injection. These
      results suggest that CIP-13F has a high inhibitory effect on the growth of OVCA
      cells via decreasing the activity and expression of APN/CD13.

PMID- 20042272
TI  - Detection of chronic lymphocytic leukemia cell surface markers using surface
      enhanced Raman scattering gold nanoparticles.
AB  - Selective targeting and detection of a hematologic malignancy, chronic
      lymphocytic leukemia, using surface enhanced Raman scattering (SERS) gold
      nanoparticles is reported. The functional nanoparticles were composed of a gold
      core onto which an optical reporter dye was adsorbed, protected from aggregation
      by grafted polyethyleneglycol, and targeted to CD19 antigen by antibodies. The
      signals were detected by dark-field microscopy and Raman spectrometry. The
      observation that the Raman signals are not disrupted by several traditional
      pathology stains indicates advantages over fluorescence methods.

PMID- 20042273
TI  - p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells.
AB  - Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid
      leukemia (CML). p21(Cip1), initially described as a cell cycle inhibitor, also
      protects from apoptosis in some models. We describe that imatinib down-regulates
      p21(Cip1) expression in CML cells. Using K562 cells with inducible p21 expression
      and transient transfections we found that p21 confers partial resistance to
      imatinib-induced apoptosis. This protection is not related to the G2-arrest
      provoked by p21, a decrease in the imatinib activity against Bcr-Abl or a
      cytoplasmic localization of p21. The results suggest an involvement of p21(Cip1)
      in the response to imatinib in CML.

PMID- 20042275
TI  - Characteristics of polycyclic aromatic hydrocarbons in indoor and outdoor
      atmosphere in the North central part of India.
AB  - Twenty-three polycyclic aromatic hydrocarbons (PAHs) were measured simultaneously
      in indoor and outdoor environment of ten homes at urban and roadside sites in the
      north central part of India during winter season (November 2006 to February
      2007). The average concentration of total PAH (TPAH) was 1946.84 ng/m(3) in
      kitchen, 1666.78 ng/m(3) in living room and 1212.57 ng/m(3) in outdoors at urban
      site, whereas at roadside site it was 2824.87 ng/m(3), 2161.26 ng/m(3)(,) and
      3294.28 ng/m(3) in kitchen, living room and outdoors respectively. The two, three
      and four ring PAHs were predominant in vapour phase, while the five, six ring
      PAHs were primarily associated with the particulate phase. The concentration
      trends of the PAHs in present study were naphthalene>2-methylnaphthalene>1
      methylnaphthalene>biphenyl>acenaphthylene in indoor and outdoor environment of
      both the sites. The spatial trend of total PAHs concentrations in the house
      located at urban sites, was kitchen>living room>outdoors whereas at roadside
      site, the trend was outdoors>kitchen>living room. Correlation analysis has been
      used to identify the sources of PAHs. The correlation between CO(2) and ratio of
      living room/outdoors (L/O) and kitchen/outdoor (K/O) of total PAHs concentration
      for two sites was found to be significant.

PMID- 20042274
TI  - ATM- and ATR-mediated response to DNA damage induced by a novel camptothecin,
      ST1968.
AB  - DNA damage response and checkpoint activation are expected to influence the
      sensitivity to DNA-damaging agents. This study was designed to investigate the
      DNA damage response to the novel camptothecin, ST1968, in two tumor cell lines
      with a different biological background (A2780 and KB), which underwent distinct
      cell cycle perturbations and cell death modalities. Following treatment with the
      camptothecin or ionizing radiation, both inducing double-strand DNA breaks, the
      ovarian carcinoma A2780 cells exhibited activation of the ATM-Chk2 pathway and
      early induction of apoptosis. In contrast, the squamous carcinoma KB cells
      exhibited activation of ATR-Chk1 pathway, a persistent G(2)/M-phase arrest,
      cellular senescence, mitotic catastrophe and delayed apoptosis, suggesting a
      defective ATM pathway. The cellular response to UV-induced DNA damage, which
      activates ATR-Chk1 pathway, was similar in the two cell lines exhibiting early
      apoptosis induction. Inhibition of ATM in A2780 cells, resulting in reduced
      phosphorylation of Chk2, enhanced ST1968-induced apoptosis, but had no effect in
      KB cells. The susceptibility to camptothecin-induced apoptosis of A2780 cells was
      likely p53-dependent but not related to the activation of the ATM pathway. In
      contrast, the inhibition of Chk1 enhanced apoptosis response in KB cell but not
      in A2780. Thus, depending on the biological context, the camptothecin activated
      ATM-Chk2 or ATR-Chk1 pathways, both having a protective role. In conclusion, our
      results are consistent with the interpretation that the modality of cell death
      response is not the critical determinant of sensitivity to camptothecins, and
      support the interest of inhibition of checkpoint kinases to improve the efficacy
      of camptothecins.

PMID- 20042276
TI  - Characterization of carbon cryogel microspheres as adsorbents for VOC.
AB  - Adsorption characteristics of carbon cryogel microspheres (CC microspheres) with
      controlled porous structure composed of mesopores (2 nm<d(p)<50 nm; d(p) is pore
      diameter) and micropores (d(p)<2 nm) were studied to examine their suitability as
      adsorbents for a volatile organic compound (VOC). The amount of toluene, as a
      model VOC, adsorbed on the CC microspheres could be changed by varying either the
      size of the mesopores or the volume of the micropores. The peak temperature of
      the temperature-programmed desorption profiles of toluene from the CC
      microspheres was higher than that from granular activated carbon (GAC) with
      numerous micropores, indicating that toluene is adsorbed more strongly on CC
      microspheres than on GAC. To permit the practical use of CC microspheres, the
      adsorption characteristic of moisture on CC microspheres and GAC were evaluated.
      The effect of adsorption of moisture on the gas permeation property of an
      adsorption module prepared from the CC microspheres was also examined.

PMID- 20042278
TI  - Contamination and congener profiles of polychlorinated biphenyls from different
      agricultural top soils in a county of the Tailake Region, China.
AB  - Hundred topsoil (0-20 cm) samples under different land use types were collected
      from a county in the Tailake Region, China and analyzed for 18 polychlorinated
      biphenyls (PCBs) including five dioxin-like PCBs. The mean concentration of total
      PCBs (SigmaPCBs) for all sites was 1.071 microg kg(-1) dry weight (dw) with a
      range of 0.016 microg kg(-1) to 4.050 microg kg(-1), and the concentration of
      total Dioxin-like PCBs (SigmaDioxin-like PCBs) was 0.352 microg kg(-1) about 33%
      of SigmaPCBs. The concentration of SigmaPCBs in paddy field (PF) soils with a
      mean of 1.63 microg kg(-1) was higher than that in vegetable soil with a mean of
      0.882 microg kg(-1), but the concentration of Dioxin-like PCBs in PF soil was
      lower than that in commercial vegetable production soil. The concentration of
      heavier weighted molecular PCB congeners (> or = penta-PCBs) in vegetable soil
      accounted for 98% of SigmaPCBs, while that in Paddy field soil for 65% of
      SigmaPCBs.

PMID- 20042277
TI  - Phosphorous removal in batch systems using ferric chloride in the presence of
      activated sludges.
AB  - The objectives of this work were: (a) to analyze the effect of alkalinity, pH and
      initial Fe:P molar ratio (Fe(0):P(0)) on the precipitation of orthophosphate
      using ferric chloride in the presence of activated sludge in order to represent
      conditions of simultaneous precipitation, and in exhausted wastewater to simulate
      conditions of post-precipitation, (b) to compare the experimental results with
      predictions obtained from a chemical equilibrium model, and (c) to propose a
      mechanistic model to determine the dose of coagulant required to achieve a given
      orthophosphate removal degree at constant pH. Results showed that the presence of
      biomass did not affect the orthophosphate precipitation; however, addition of
      ferric chloride caused a drop of pH to values not compatible with the normal
      activity of activated sludges. For this reason, the wastewater was supplemented
      with NaHCO(3); when 1gL(-1) NaHCO(3) was added, orthophosphate removals higher
      than 97% and pH above 6.2 were obtained using Fe(0):P(0)=1.9. Precipitation
      assays at constant pH showed that Fe(III) hydrolysis and FePO(4) precipitation
      reaction compete with each other. Calculations using a chemical equilibrium model
      (CHEAQS) predicted that ferric phosphate precipitation should not take place if
      pH is higher than about 7.8. However, experimental results showed that ferric
      phosphate precipitation occurred even at pH 9. For this reason, a mechanistic
      model was proposed to predict orthophosphate concentrations as a function of
      Fe(0):P(0) at constant pH. The model can be applied to calculate the minimum
      Fe(III) concentration required to achieve a given discharge limit for
      orthophosphate as a function of its initial concentration and pH.

PMID- 20042279
TI  - Peat humic substances enriched with nutrients for agricultural applications:
      competition between nutrients and non-essential metals present in tropical soils.
AB  - Improved agricultural productivity, and reduction of environmental impacts,
      require studies of the interactions between different soil components.
      Fertilizers marketed as "organic" or "natural", such as peats or humic substances
      (HS) extracted from peats, are enriched with macro and micronutrients that,
      according to the manufacturers, are released to the plant in accordance with its
      needs. This work investigates the complexation capacity of HS for macro and
      micronutrient metal species, considering the competition, for HS complexation
      sites, between non-essential metals (aluminium and lead), present in the soil,
      and the nutrients. Humic substances were found to possess strong affinities for
      Pb(II) and Al(III), forming stable complexes, with concomitant release of
      complexed nutrients. Although HS are already used commercially as organic
      fertilizers, further studies of methods of HS enrichment, aimed at avoiding
      losses, are highly desirable from environmental and economic perspectives.

PMID- 20042280
TI  - Electro-coagulation-flotation process for algae removal.
AB  - Algae in surface water have been a long-term issue all over the world, due to
      their adverse influence on drinking water treatment process as well as drinking
      water quality. The algae removal by electro-coagulation-flotation (ECF)
      technology was investigated in this paper. The results indicated that aluminum
      was an excellent electrode material for algae removal as compared with iron. The
      optimal parameters determined were: current density=1 mA/cm(2), pH=4-7, water
      temperature=18-36 degrees C, algae density=0.55 x 10(9)-1.55 x 10(9) cells/L.
      Under the optimal conditions, 100% of algae removal was achieved with the energy
      consumption as low as 0.4 kWh/m(3). The ECF performed well in acid and neutral
      conditions. At low initial pH of 4-7, the cell density of algae was effectively
      removed in the ECF, mainly through the charge neutralization mechanism; while the
      algae removal worsened when the pH increased (7-10), and the main mechanism
      shifted to sweeping flocculation and enmeshment. The mechanisms for algae removal
      at different pH were also confirmed by atomic force microscopy (AFM) analysis.
      Furthermore, initial cell density and water temperature could also influence the
      algae removal. Overall, the results indicated that the ECF technology was
      effective for algae removal, from both the technical and economical points of
      view.

PMID- 20042281
TI  - Sorption kinetics and equilibrium for the removal of nickel ions from aqueous
      phase on calcined Bofe bentonite clay.
AB  - In this paper the kinetics and dynamics of nickel adsorption on calcined Bofe
      bentonite clay were studied. The clay was characterized through EDX, surface area
      (BET) and XRD analysis. The influence of parameters (pH, amount of adsorbent,
      adsorbate concentration and temperature) was investigated. Kinetic models were
      evaluated in order to identify potential adsorption process mechanisms. The
      Langmuir and Freundlich models were utilized for the analysis of adsorption
      equilibrium. Thermodynamic parameters were assessed as a function of the process
      temperature. The kinetics data were better represented by the second-order model.
      The process was found to be strongly influenced by the factors studied. The Bofe
      clay removed nickel with maximum adsorption capacity of 1.91 mg metal/g of clay
      (20 degrees C; pH 5.3) and that the thermodynamic data indicated that the
      adsorption reaction is spontaneous and of an exothermal nature. The Langmuir
      model provided the best fit for sorption isotherms.

PMID- 20042282
TI  - Cadmium accumulation and growth responses of a poplar (Populus deltoidsxPopulus
      nigra) in cadmium contaminated purple soil and alluvial soil.
AB  - To characterize the phytoextraction efficiency of a hybrid poplar (Populus
      deltoidsxPopulus nigra) in cadmium contaminated purple soil and alluvial soil, a
      pot experiment in field was carried out in Sichuan basin, western China. After
      one growing period, the poplar accumulated the highest of 541.98+/-19.22 and
      576.75+/-40.55 microg cadmium per plant with 110.77+/-12.68 and 202.54+/-19.12 g
      dry mass in these contaminated purple soil and alluvial soil, respectively.
      Higher phytoextraction efficiency with higher cadmium concentration in tissues
      was observed in poplar growing in purple soil than that in alluvial soil at
      relative lower soil cadmium concentration. The poplar growing in alluvial soil
      had relative higher tolerance ability with lower reduction rates of morphological
      and growth characters than that in purple soil, suggesting that the poplar
      growing in alluvial soil might display the higher phytoextraction ability when
      cadmium contamination level increased. Even so, the poplars exhibited obvious
      cadmium transport from root to shoot in both soils regardless of cadmium
      contamination levels. It implies that this examined poplar can extract more
      cadmium than some hyperaccumulators. The results indicated that metal
      phytoextraction using the poplar can be applied to clean up soils moderately
      contaminated by cadmium in these purple soil and alluvial soil.

PMID- 20042283
TI  - Synthesis of nanocrystalline anatase TiO2 by one-pot two-phase separated
      hydrolysis-solvothermal processes and its high activity for photocatalytic
      degradation of rhodamine B.
AB  - Si-doped and un-doped nanocrystalline TiO(2) samples have been synthesized by
      simple one-pot water-organic two-phase separated hydrolysis-solvothermal (HST)
      processes, and characterized by XRD, BET, TEM, FT-IR, DRS and surface
      photovoltage techniques. The effects of the solvothermal temperature and Si
      doping on the anatase thermal stability, and on the photocatalytic activity for
      degrading rhodamine B were investigated in detail. The results show that, as the
      solvothermal temperature rises, the crystallinity and thermal stability of the
      resulting nano-sized anatase TiO(2) gradually increase. Noticeably, the as
      prepared TiO(2) obtained at appropriate solvothermal temperature (160 degrees C)
      exhibits high photocatalytic activity. Moreover, although Si doping does not
      improve the photocatalytic activity of the as-prepared anatase TiO(2), it greatly
      enhances the anatase thermal stability and inhibits crystallite growth during the
      process of post-thermal treatment. Interestingly, the Si-doped TiO(2) post
      treated at high temperature displays much higher photocatalytic activity than
      commercial P25 TiO(2). It is clearly demonstrated that the joint effects of high
      anatase crystallinity and large surface area lead to high photocatalytic
      activity. This work provides a simple and effective strategy for the synthesis of
      high-performance TiO(2)-based functional nanomaterials.

PMID- 20042284
TI  - Clofibric acid degradation in UV254/H2O2 process: effect of temperature.
AB  - The degradation of clofibric acid (CA) in UV(254)/H(2)O(2) process under three
      temperature ranges, i.e. T1 (9.0-11.5 degrees C), T2 (19.0-21.0 degrees C) and T3
      (29.0-30.0 degrees C) was investigated. The effects of solution constituents
      including NO(3)(-) and HCO(3)(-) anions, and humic acid (HA) on CA degradation
      were evaluated in Milli-Q waters. CA degradation behaviors were simulated with
      the pseudo-first-order kinetic model and the apparent rate constant (k(ap)) and
      half-life time (t(1/2)) were calculated. The results showed that higher
      temperature would favor CA degradation, and CA degradation was taken place mostly
      by indirect oxidation through the formation of OH radicals in UV(254)/H(2)O(2)
      process. In addition, the effects of both NO(3)(-) and HCO(3)(-) anions at two
      selected concentrations (1.0x10(-3) and 0.1 mol L(-1)) and HA (20 mg L(-1)) on CA
      degradation were investigated. The results showed that HA had negative effect on
      CA degradation, and this effect was much more apparent under low temperature
      condition. On the other hand, the inhibitive effect on CA degradation at both
      lower and higher concentrations of bicarbonate was observed, and this inhibitive
      effect was much more apparent at higher bicarbonate concentration and lower
      temperature condition. While, at higher nitrate concentration the inhibitive
      effect on CA degradation under three temperature ranges was observed, and with
      the temperature increase this negative effect was apparently weakened. However,
      at lower nitrate concentration a slightly positive effect on CA degradation was
      found under T2 and T3 conditions. Moreover, when using a real wastewater
      treatment plant (WWTP) effluent spiked with CA over 99% of CA removal could be
      achieved under 30 degrees C within only 15 min compared with 40 and 80 min under
      20 and 10 degrees C respectively, suggesting a significant promotion in CA
      degradation under higher temperature condition. Therefore, it can be concluded
      that temperature plays an important role in CA degradation in UV/H(2)O(2)
      process.

PMID- 20042285
TI  - Decolorization of Acid Red 1 by Fenton-like process using rice husk ash-based
      catalyst.
AB  - The decolorization of Acid Red 1 (AR1) in aqueous solution was investigated by
      Fenton-like process. The effect of different reaction parameters such as
      different iron ions loading on rice husk ash (RHA), dosage of catalyst, initial
      pH, the initial hydrogen peroxide concentration ([H(2)O(2)](o)), the initial
      concentration of AR1 ([AR1](o)) and the reaction temperature on the
      decolorization of AR1 was studied. The optimal reacting conditions were found to
      be 0.070 wt.% of iron (III) oxide loading on RHA, dosage of catalyst=5.0 g L(-1),
      initial pH=2.0, [H(2)O(2)](o)=8 mM, [AR1](o)=50 mg L(-1) at temperature 30
      degrees C. Under optimal condition, 96% decolorization efficiency of AR1 was
      achieved within 120 min of reaction.

PMID- 20042286
TI  - Fenton-like oxidation of reactive black 5 solution using iron-Montmorillonite K10
      catalyst.
AB  - Decolorization of reactive azo dye, reactive black 5 (RB5), was conducted using
      Fe(III) immobilized on Montmorillonite K10 (MK10) as a catalyst in the presence
      of H(2)O(2) using Fenton-like oxidation process. The effect of different
      parameters such as iron ions loading on supported catalyst, catalyst dosage,
      initial pH of dye solution, initial concentration of H(2)O(2) and dye and
      reaction temperature on the decolorization efficiency of the process were
      studied. The results indicated that by using 12 mM of H(2)O(2) and 3.50 g L(-1)
      of the 0.11 wt.% Fe(III) oxide on MK10 catalyst at pH of 2.5, 99% of
      decolorization efficiency was achieved within 150 min in a batch process.

PMID- 20042287
TI  - Development of a new controlled pesticide delivery system based on neem leaf
      powder.
AB  - In order to minimize the agro-environmental pollution and health hazards caused
      by pesticides, in the present study, the neem leaf powder "(NLP)", a bio
      pesticide, has been exploited to develop the pesticide delivery devices. The
      presence of neem in the formulations along with the pesticide may enhance the
      potential of these systems due to its inherent pesticidal activity. We have
      prepared the NLP and alginate based beads by using CaCl(2) as crosslinker. To
      study the effect of composition of the beads on the release dynamics of fungicide
      (thiram), beads were prepared by varying the amount of NLP and crosslinker. The
      beads formed were characterized with Fourier transform infrared spectroscopy
      (FTIR), scanning electron micrograph (SEM), energy dispersion analysis by X-rays
      (EDAX), thermogravimetric analysis and swelling study. Formulation
      characteristics such as entrapment efficiency, bead size, percentage equilibrium
      swelling of the beads and diffusion mechanism for thiram release have been
      evaluated. Maximum (78.33+/-2.89)% swelling has occurred in the beads prepared
      with 1.5% NLP, 2.5% alginate and 0.1M crosslinker solution. In most of the
      formulations the values for the diffusion exponent 'n' have been obtained >1 and
      hence the release of fungicides occurred through Case II diffusion mechanism.

PMID- 20042288
TI  - Industrial dye degradation and detoxification by basidiomycetes belonging to
      different eco-physiological groups.
AB  - Twenty-five basidiomycetes belonging to 17 species and ascribable to different
      eco-physiological groups were screened for their ability to decolorize 9
      commercially important industrial dyes comprising a variety of anthraquinonic,
      azoic and phtalocyanin chromophores. The influence of the culture medium,
      particularly its C:N ratio, on decolourisation capacity was considered on solid
      substrate. Three strains of Bjerkandera adusta performed the highest
      decolourisation yields being able to degrade all dyes on all media and to produce
      a wide spectrum of oxidative enzyme activities. Hence, B. adusta strains were
      selected for further experiments in liquid cultures together with other 6 fungi
      that resulted effective in the decolourisation of the largest number of molecules
      in the broadest spectrum of cultural conditions. Particularly B. adusta MUT 3060
      was found very effective (decolourisation percentage over 90%) in the treatment
      of simulated effluents composed of single and mixed dyes at high concentration
      (1000 mg/l). Peroxidase activity dependent (up to 362 U/l) and independent from
      manganese (up to 57 U/l) were detected during the decolourisation process. The
      Lemna minor toxicity test showed a significant reduction of toxicity after the
      fungal treatment indicating that decolourisation corresponded to an actual
      detoxification of the wastewater.

PMID- 20042289
TI  - Degradation of trichloroethylene (TCE) by nanoscale zero-valent iron (nZVI)
      immobilized in alginate bead.
AB  - Nowadays, many researchers have studied the environmental application of the
      nanoscale zero-valent iron (nZVI) and several field applications for the
      groundwater remediation have been reported. Still, there are many concerns on the
      fate and transport of the nZVI and the corresponding risks. To avoid such
      concerns, it was investigated to immobilize nZVI in a support and then it was
      applied to degrade trichloroethylene (TCE). The nZVI and palladium-doped nZVI
      (Fe(0)- and Fe/Pd-alginate) were immobilized in the alginate bead where ferric
      and barium ions are used as the cross-linking cations of the bead. According to
      TEM (transmission electron microscopy), the size of the immobilized ZVI was as
      small as a few nanometers. From the surface analysis of the Fe/Pd-alginate, it is
      found that the immobilized nZVI has the core-shell structure. The core is
      composed of single crystal Fe(0), while most of irons on the surface are oxidized
      to Fe(3+). When 50 g/L of Fe/Pd-alginate (3.7 g Fe/L) was introduced to the
      aqueous solution, >99.8% of TCE was removed and the release of metal from the
      support was <3% of the loaded iron. The removal of TCE by Fe/Pd-alginate followed
      pseudo-first-order kinetics. The observed pseudo-first-order reaction constant
      (k(obs)) of Fe/Pd-alginate was 6.11 h(-1) and the mass normalized rate constant
      (k(m)) was 1.6 L h(-1) g(-1). The k(m) is the same order of magnitude with that
      of iron nanoparticles. In conclusion, it is considered that Fe/Pd-alginate can be
      used efficiently in the treatment of chlorinated solvent.

PMID- 20042290
TI  - Adsorption of volatile organic compounds onto activated carbon cloths derived
      from a novel regenerated cellulosic precursor.
AB  - Activated carbon cloths (ACC) were prepared from lyocell, a novel regenerated
      cellulose nanofibre fabric, by phosphoric acid activation in inert atmosphere at
      two different final thermal treatment temperatures (864 and 963 degrees C).
      Benzene, toluene and n-hexane isotherms at 298 and 273K were measured in order to
      gain insight into the porous structure of the ACC and to evaluate their
      performance for the removal of volatile organic compounds (VOCs). The Dubinin
      Radushkevich equation was employed to evaluate textural parameters of the ACC.
      The textural characteristics of the ACC were compared with those previously
      determined from nitrogen (77K) and carbon dioxide (273K) adsorption data. The
      samples were essentially microporous. The textural parameters calculated from the
      hydrocarbon isotherms were in good agreement with those evaluated from nitrogen
      isotherms for the ACC with the wider microporosity. Additionally, the Freundlich
      model provided a good description of the experimental isotherms for the three
      volatile organic compounds. The ACC obtained at the higher temperature exhibited
      a larger adsorption capacity. The ACC were also electrically conductive and
      showed potential for regeneration by the Joule effect, as determined from
      macroscopic electrical measurements before and after n-hexane adsorption.

PMID- 20042291
TI  - Removal of lead(II) from aqueous solutions using carbonate hydroxyapatite
      extracted from eggshell waste.
AB  - Carbonate hydroxyapatite (CHAP) synthesized from eggshell waste was used for
      removing lead ion from aqueous solutions. The effects of pH, contact time and
      initial concentration were studied in batch experiments. The maximum uptake of
      lead ion was obtained at pH 6.0. Adsorption equilibrium was established by 60
      min. The pseudo-first order, pseudo-second order and intraparticle diffusion
      kinetic models were applied to study the kinetics of the sorption processes. The
      pseudo-second order kinetic model provided the best correlation (R(2)>0.9991) of
      the used experimental data compared to the pseudo-first order and intraparticle
      diffusion kinetic models. The adsorption of lead ion by CHAP increased as the
      initial concentration of lead ion increased in the medium. The maximum lead ion
      adsorbed was found to be 101 mg g(-1). It was found that the adsorption of Pb(II)
      on CHAP was correlated well (R(2)=0.9995) with the Langmuir equation as compared
      to Freundlich isotherm equation under the concentration range studied. This study
      indicated that CHAP could be used as an efficient adsorbent for removal of lead
      ion from aqueous solution.

PMID- 20042292
TI  - Experimental investigation on influence of smoke venting velocity and vent height
      on mechanical smoke exhaust efficiency.
AB  - A set of burning experiments were conducted to investigate the influence of smoke
      vent height and exhausting velocity on mechanical smoke exhausting efficiency.
      Results have shown that the smoke exhausting process becomes more efficient due
      to the increased smoke vent height and the decreased exhausting velocity, which
      eliminate the plug-holing issue with fewer disturbances on the smoke layer
      interface. For each certain exhausting velocity, there is a critical value of
      distance between the vent and the bottom of the smoke layer. When the distance is
      less than the critical value, the smoke exhausting is inefficient, and the
      efficiency decreases sharply as the distance decreases. Contrarily, when the
      distance is greater than the critical value, a good efficiency can be acquired
      and the exhausted smoke increased relatively slowly as the distance increases. A
      critical Froude number, proposed by Hinkley to predict the onset of plug-holing
      effect in gravity venting systems, was validated in the experiments. However, the
      experimental results indicate that in the tests without the plug-holing, the
      fresh air entrained due to smoke exhausting is up to 48% of the mechanical
      exhausting rate.

PMID- 20042295
TI  - Characterization of the excretory/secretory products of Dermatobia hominis
      larvae, the human bot fly.
AB  - Proteolytic activity in excretory/secretory products (ESP) of first- (L1), second
      (L2) and third-instar (L3) larvae of Dermatobia hominis was analyzed through
      gelatin-gel and colorimetric enzyme assays with the chromogenic substrates
      azocasein and BApNA. The functional characterization of proteases was based on
      inhibition assays including synthetic inhibitors. ESP were obtained from new
      hatched larvae reared in the laboratory and from second- and third-instar larvae
      removed from naturally infested cattle. Gelatin-gel analysis evidenced few bands
      of proteolysis, predominantly of high apparent molecular masses, in ESP of L1,
      whereas in the gel of L2 and L3 ESP there was a wide range of proteolytic
      activity most of them not resolved in a single species. Azocasein assays revealed
      a progressive increase of protease activity from first- to third-instar larvae.
      Protease inhibitor assays revealed a predominance of metalloproteases in L1 ESP
      that could be related to a skin penetration process and to a diversion of host
      immune response. The predominance of serine proteases in L2 and L3 and the great
      tryptic activity presented by L3 ESP were attributed to an increasing trophic
      activity by the growing larvae, since the viability of adult flies strictly
      depends on larval abilities to assimilate nutrients from the host. Taking
      together, these results suggest that Dematobia larvae secrete/excrete different
      proteases that may be related to diverse functions during host penetration and
      infestation, which reinforces the relevance of the study of such proteolytic
      enzymes.

PMID- 20042296
TI  - Acaricidal activity of extracts from Petiveria alliacea (Phytolaccaceae) against
      the cattle tick, Rhipicephalus (Boophilus) microplus (Acari: ixodidae).
AB  - The acaricidal activity of crude extracts and fractions from stems and leaves of
      Petiveria alliacea (Phytolaccaceae) was carried out on larvae and adults of the
      cattle tick Rhipicephalus (Boophilus) microplus using the larval immersion test
      (LIT) and adult immersion test (AIT), respectively. Methanolic extracts of stems
      and leaves of P. alliacea showed 100% mortality on the LIT bioassay. On the other
      hand, methanolic extracts of leaves and stem on the AIT test showed 26% and 86%
      of mortality, respectively, egg laying inhibition of 40% and 91%, respectively
      and hatchability inhibition of 26% and 17%, respectively. Purification of the
      active stem methanolic extract showed that the activity was present in the n
      hexane non-polar fraction. Bioassay-guided purification of the n-hexane fraction
      produced 10 semi-purified fractions; fraction B had the highest activity against
      tick larvae (100% mortality). Gas chromatography-mass spectrometry demonstrated
      that the chemical composition of the active fraction B samples were mainly
      composed of benzyltrisulfide (BTS) and benzyldisulfide (BDS). These metabolites
      might be responsible for the acaricidal activity of stem extract of P. alliacea.
      However, further experiments to evaluate the acaricidal activity of BTS and BDS
      on larvae and adults of R. (B.) microplus are needed. Our results showed that P.
      alliacea is a promising biocontrol candidate as acaricide against R. (B.)
      microplus resistant strains.

PMID- 20042297
TI  - The effect of gonadectomy on prepulse inhibition and fear-potentiated startle in
      adolescent rhesus macaques.
AB  - Sex steroids, such as testosterone, can regulate brain development, cognition and
      modify psychiatric conditions. However, the role of adolescent testosterone in
      the emergence of cognitive deficits relevant to psychiatric illness has not been
      directly studied in primates. We examined whether removing testosterone during
      adolescence in rhesus macaques would affect prepulse inhibition (PPI) and fear
      potentiated startle (FPS), which are translational tests of cognition affected in
      psychiatric disorders. Prepubertal macaques (30 months old) were castrated (n=6)
      or sham operated (n=6), and PPI and (FPS) were tested before the onset of puberty
      (34 months old) and after the pubertal surge in sex hormones 16 months later (50
      months old). As expected there were no differences between the gonadectomized and
      intact groups' level of startle amplitude, PPI or (FPS) before puberty. After
      puberty, the intact group displayed substantially less PPI than the
      gonadectomized group, consistent with evidence that PPI is attenuated by
      endogenous increases in sex hormones. At the end of the study, testosterone among
      the intact monkeys was also correlated with tyrosine hydroxylase levels in the
      putamen, suggesting the attenuation of PPI by gonadal sex hormones may be
      influenced by subcortical dopamine. Thus, puberty involves significant increases
      in sex hormones, which in turn may modulate subcortical dopamine synthesis and
      affect cognitive functions impaired in psychiatric illnesses such as
      schizophrenia.

PMID- 20042298
TI  - Can Epstein-Barr virus infection be the primary etiological factor to
      nasopharyngeal carcinoma?

PMID- 20042300
TI  - dltA gene mutation in the teichoic acids alanylation system of Lactococcus
      garvieae results in diminished proliferation in its natural host.
AB  - The dltABCD cluster is involved in the d-alanylation of teichoic acids in gram
      positive bacteria. In order to determine the role of this alanylation in the
      physiology and virulence of Lactococcus garvieae, a previously isolated dltA
      Delta Tn917 signature tagged mutagenesis (STM) clone was analyzed. RT-PCR results
      revealed that dltABCD genes form an operon. No major differences could be
      established between the parental and mutant strains with respect to growth rate,
      autolytic properties, and susceptibility to acid conditions, lysozyme treatment,
      anionic detergents, or oxidant agents. However, the dltA mutant was more
      susceptible to nisin than the parental strain, with minimum inhibitory
      concentration (MIC) values of 8 and 16 microg/ml, respectively. Less
      proliferation of the mutant was observed in in vivo competence index experiments
      (CI=0.08). Furthermore, the mutant strain had a 50% lethal dose (LD(50)) 3-fold
      that of the parental strain. These results, together with the fact that the dltA
      Delta Tn917 mutant was isolated as a STM clone, reveal that the dltA locus of
      Lactococcus garvieae is required for full growth and pathogenesis on rainbow
      trout.

PMID- 20042299
TI  - Estimating risk of alcohol dependence using alcohol screening scores.
AB  - Brief alcohol counseling interventions can reduce alcohol consumption and related
      morbidity among non-dependent risky drinkers, but more intensive alcohol
      treatment is recommended for persons with alcohol dependence. This study
      evaluated whether scores on common alcohol screening tests could identify
      patients likely to have current alcohol dependence so that more appropriate
      follow-up assessment and/or intervention could be offered. This cross-sectional
      study used secondary data from 392 male and 927 female adult family medicine
      outpatients (1993-1994). Likelihood ratios were used to empirically identify and
      evaluate ranges of scores of the AUDIT, the AUDIT-C, two single-item questions
      about frequency of binge drinking, and the CAGE questionnaire for detecting DSM
      IV past-year alcohol dependence. Based on the prevalence of past-year alcohol
      dependence in this sample (men: 12.2%; women: 5.8%), zones of the AUDIT and AUDIT
      C identified wide variability in the post-screening risk of alcohol dependence in
      men and women, even among those who screened positive for alcohol misuse. Among
      men, AUDIT zones 5-10, 11-14 and 15-40 were associated with post-screening
      probabilities of past-year alcohol dependence ranging from 18 to 87%, and AUDIT-C
      zones 5-6, 7-9 and 10-12 were associated with probabilities ranging from 22 to
      75%. Among women, AUDIT zones 3-4, 5-8, 9-12 and 13-40 were associated with post
      screening probabilities of past-year alcohol dependence ranging from 6 to 94%,
      and AUDIT-C zones 3, 4-6, 7-9 and 10-12 were associated with probabilities
      ranging from 9 to 88%. AUDIT or AUDIT-C scores could be used to estimate the
      probability of past-year alcohol dependence among patients who screen positive
      for alcohol misuse and inform clinical decision-making.

PMID- 20042301
TI  - Milk concentration improves Bluetongue antibody detection by use of an indirect
      ELISA.
AB  - A national Bluetongue antibody surveillance in cattle through bulk milk was
      conducted in Switzerland between July 2007 and June 2008. Using ID Screen
      Bluetongue Milk ELISA (ID VET, Montpellier, France), samples from 15 out of 210
      dairy farms at least once gave a positive result. In only three of these herds
      bluetongue positive animals were found. Therefore, specificity for bulk milk was
      not as good as expected and when individual milk samples were tested, it was even
      lower. As further investigations of positive results were time-consuming and no
      other ELISA was available at that time, we aimed at discriminating false from
      true positive samples with a confirmatory test using a protein precipitation
      method followed by retesting with the same ELISA. Additionally, we examined
      whether testing of single milk samples can reliably be used to assess status of
      cows, and whether sampling at the beginning or at the end of milking, as well as
      freezing and thawing of the milk could influence the performance of the test.
      Screening with ID VET milk ELISA and confirmatory testing after protein
      precipitation yielded a clear increase of specificity without any loss of
      sensitivity in both bulk and single milk samples. This testing scheme allowed
      minimizing follow-up investigations by blood testing. Antibody levels in plasma
      and milk showed a good correlation. Tested by logistic regression, none of the
      possible influencing factors (time point of sample collection, freezing, or milk
      content of the samples) had a significant influence on the test performance.

PMID- 20042302
TI  - Assessing the antimicrobial susceptibility of bacteria obtained from animals.

PMID- 20042303
TI  - Cool-weather activity of the forensically important hairy maggot blow fly
      Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) on carrion in Upstate
      South Carolina, United States.
AB  - The hairy maggot blow fly Chrysomya rufifacies (Macquart) (Diptera:
      Calliphoridae) has expanded its range in the United States since its introduction
      into Texas (ca. 1980) and has been collected in 15 states. We investigated the
      bionomics of immature and adult C. rufifacies collected from carcasses of a
      raccoon Procyon lotor (Linnaeus) and white-tailed deer Odocoileus virginianus
      Zimmerman in Upstate South Carolina during November 2007, and used these insects
      to estimate the minimum period of insect activity. Puparia of C. rufifacies were
      collected from deer carrion; 28% were parasitized by Nasonia vitripennis (Walker)
      (Hymenoptera: Pteromalidae). The mean daily ambient temperature during this study
      was 11.4+/-1.02 degrees C, representing the lowest recorded mean temperature for
      adult activity of C. rufifacies; adults of C. rufifacies were observed flying
      among the carcasses at 9.0 degrees C. Although C. rufifacies is considered a warm
      weather blow fly, researchers should be aware of its activity at suboptimal
      conditions, behavior that might aid its expansion into more northern areas.

PMID- 20042304
TI  - Double reversing Z-plasty with inferiorly widening stomaplasty for the management
      of tracheostomal stenosis.
AB  - OBJECTIVES: To present a surgical technique for the management of tracheostomal
      stenosis: double reversing Z-plasty with inferiorly widening stomaplasty.
      METHODS: This study was a retrospective review of five patients (four males, one
      female) submitted for tracheostomal widening procedure using "double reversing Z
      plasty with inferiorly widening stomaplasty" at our department between May 2003
      and April 2009. Skin incision was made on each lateral side of the stoma. The
      skin flap was elevated, and the subcutaneous and scar tissue at the infrastomal
      area was removed along with the redundant skin. Vertical incision was made on
      each side of the trachea as a mirror image, and the trachea was splayed. The
      inferiorly mobilized trachea was sutured to the new tissue bed inferior to the
      stoma, and both skin flaps were secured to the depths of the tracheal cut (double
      reversing Z-plasty). RESULTS: All five patients showed widened tracheostoma
      without any complications, and their phonatory prostheses functioned well after
      the procedure. In no case was it necessary to keep the tracheal tubes beyond the
      first day after the surgery. CONCLUSION: This technique, "double reversing Z
      plasty with inferiorly widening stomaplasty", provides a safe procedure for
      enlarging the tracheostomal size and easing the excessive tension without
      disturbing the posterosuperior stomal profile and the tracheoesophageal puncture
      for phonatory prosthesis.

PMID- 20042305
TI  - [Valuation of innovation: a new challenge for the structures of care, an
      opportunity for everybody...].

PMID- 20042306
TI  - [Bartonella henselae, an ubiquitous agent of proteiform zoonotic disease].
AB  - Bartonella henselae is the causative agent of cat scratch disease, a human
      infection usually characterized by persistent regional lymphadenopathy. It is
      transmitted to humans by cat scratches or bites. Cats are the major reservoir for
      this bacterium thus B. henselae has a worldwide distribution. The bacterial
      pathogenicity may bay emphasized by the immune status of the infected host.
      Angiomatosis or hepatic peliosis are the most frequent clinical manifestations in
      immunocompromised patients. B. henselae is also responsible for endocarditis in
      patients with valvular diseases, and may induce various clinical presentations
      such as: bacteriemia, retinitis, musculoskeletal disorders, hepatic or splenic
      diseases, encephalitis, or myocarditis. Several diagnostic tools are available;
      they may be combined and adapted to every clinical setting. B. henselae is a
      fastidious bacterium; its diagnosis is mainly made by PCR and blood tests. No
      treatment is required for the benign form of cat scratch disease. For more severe
      clinical presentations, the treatment must be adapted to every clinical
      presentation.

PMID- 20042307
TI  - Quantitative diffusion tensor deterministic and probabilistic fiber tractography
      in relapsing-remitting multiple sclerosis.
AB  - PURPOSE: Our aim was to study the quantitative fiber tractography variations and
      patterns in patients with relapsing-remitting multiple sclerosis (RRMS) and to
      assess the correlation between quantitative fiber tractography and Expanded
      Disability Status Scale (EDSS). MATERIAL AND METHODS: Twenty-eight patients with
      RRMS and 28 age-matched healthy volunteers underwent a diffusion tensor MR
      imaging study. Quantitative deterministic and probabilistic fiber tractography
      were generated in all subjects. And mean numbers of tracked lines and fiber
      density were counted. Paired-samples t tests were used to compare tracked lines
      and fiber density in RRMS patients with those in controls. Bivariate linear
      regression model was used to determine the relationship between quantitative
      fiber tractography and EDSS in RRMS. RESULTS: Both deterministic and
      probabilistic tractography's tracked lines and fiber density in RRMS patients
      were less than those in controls (P<.001). Both deterministic and probabilistic
      tractography's tracked lines and fiber density were found negative correlations
      with EDSS in RRMS (P<.001). The fiber tract disruptions and reductions in RRMS
      were directly visualized on fiber tractography. CONCLUSION: Changes of white
      matter tracts can be detected by quantitative diffusion tensor fiber
      tractography, and correlate with clinical impairment in RRMS.

PMID- 20042308
TI  - Development and validation of a LC-MS/MS method for determination of bivalirudin
      in human plasma: Application to a clinical pharmacokinetic study.
AB  - A simple, sensitive and rapid LC-MS/MS method has been developed and validated
      for the identification and quantification of bivalirudin in human plasma using
      nafarelin as the internal standard. Following protein precipitation with
      methanol, the analytes were separated on a C(18) column interfaced with a triple
      quadrupole tandem mass spectrometer using positive electrospray ionization.
      Quantification of bivalirudin was conducted by multiple reaction monitoring (MRM)
      of the transitions of m/z 1091.4-->(356.4+227.4) for bivalirudin and m/z 662.4-
      >328.5 for IS. The lower limit of quantification was 1.25ng/ml, and the assay
      exhibited a linear range of 1.25-500ng/ml. The developed assay method was
      successfully applied to a pharmacokinetic (PK) study in healthy volunteers after
      intravenous administration of bivalirudin.

PMID- 20042309
TI  - A total laparoscopic technique for endovascular thoracic stent graft deployment.
AB  - BACKGROUND: Limitations of endovascular thoracic aneurysm treatment include
      small, tortuous, or severely calcified iliac arteries. We present our experience
      with a total laparoscopic access to deploy thoracic endografts. METHODS: A total
      laparoscopic left retrocolic approach was used in all cases. A Dacron conduit was
      laparoscopically sutured to either the iliac artery or to the aorta directly. The
      endograft was inserted through this conduit. After graft deployment, the Dacron
      prosthesis was tunneled to the groin and anastomosed with the femoral artery.
      RESULTS: The laparoscopic procedure could successfully be performed in 11
      patients. In six cases, the aorta was used as an access and in five patients, the
      iliac arteries were preferred. In one of these cases, the right iliac artery was
      used for deployment of the endograft. After successful aorto- or ileo-femoral
      bypass grafting, all patients had an improvement of their ankle brachial index
      postoperatively. The mean operative time was almost four hours, including
      laparoscopy, laparoscopic anastomosis, endograft deployment, and femoral artery
      anastomosis or profundaplasty. CONCLUSION: Totally laparoscopic assisted graft
      implantation in aorta or iliac arteries provides a safe and effective access for
      the endovascular delivery system. However, further evaluation and long follow-up
      are necessary to ensure the potential advantages of this technique. It is a less
      invasive option to overcome access-related problems with thoracic endograft
      deployment, giving the patient the advantage of a totally minimal invasive
      procedure.

PMID- 20042310
TI  - A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant
      treatment of patients with locally advanced resectable rectal cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) reduces local tumor recurrence in
      locally advanced rectal cancer (LARC). This phase II study assessed neoadjuvant
      cetuximab with capecitabine-based CRT in LARC. METHODS: Patients with stage
      II/III LARC received capecitabine 1250 mg/m(2) twice daily for 2 weeks followed
      by intravenous cetuximab 400 mg/m(2) at week 3, then weekly intravenous 250
      mg/m(2) cetuximab plus CRT including capecitabine 825 mg/m(2) twice daily
      (including weekends during radiotherapy) with radiotherapy of 45 Gy (25 x 1.8
      Gy), 5 days a week for 5 weeks. Total mesorectal excision was scheduled 4-6 weeks
      following completion of CRT. The primary endpoint was pathological complete
      response (pCR). RESULTS: Thirty-seven patients were eligible for safety and
      efficacy. TMN staging at baseline was: T4N2, 11%; T3N2, 40%; T2N2, 3%; T3N1, 35%;
      T2N1, 3% and T3N0 8%. The most common adverse events included, grade 1/2
      acneiform skin rash (86%), and grade 3 radiodermatitis, (16%), diarrhea (11%) and
      hypersensitivity (5%). pCR was achieved in 3 patients (8%). Overall-, T- and N
      downstaging rates were 73%, 57% and 81% respectively. Total sphincter
      preservation rate was 76%, and 53% in 17 patients whose tumors were located
      within 5 cm from the anal verge. Non-fatal perioperative complications occurred
      in 13 patients (35%) with delayed wound healing occurring in 6 patients (16%).
      One death was recorded due to sepsis following colonic necrosis. CONCLUSION:
      Neoadjuvant cetuximab with capecitabine-based CRT is tolerable in patients with
      resectable LARC. Whilst the pCR rate was similar to recent reports, a high
      pathological downstaging rate was achieved.

PMID- 20042311
TI  - A computer simulation of employee vaccination to mitigate an influenza epidemic.
AB  - BACKGROUND: Better understanding the possible effects of vaccinating employees is
      important and can help policymakers and businesses plan vaccine distribution and
      administration logistics, especially with the current H1N1 influenza vaccine in
      short supply. PURPOSE: This article aims to determine the effects of varying
      vaccine coverage, compliance, administration rates, prioritization, and timing
      among employees during an influenza pandemic. METHODS: As part of the H1N1
      influenza planning efforts of the Models of Infectious Disease Agent Study
      network, an agent-based computer simulation model was developed for the
      Washington DC metropolitan region, encompassing five metropolitan statistical
      areas. Each simulation run involved introducing 100 infectious individuals to
      initiate a 1.3 reproductive-rate (R(0)) epidemic, consistent with H1N1 parameters
      to date. Another set of scenarios represented a R(0)=1.6 epidemic. RESULTS: An
      unmitigated epidemic resulted in substantial productivity losses (a mean of
      $112.6 million for a serologic 15% attack rate and $193.8 million for a serologic
      25% attack rate), even with the relatively low estimated mortality impact of
      H1N1. Although vaccinating Advisory Committee on Immunization Practices-defined
      priority groups resulted in the largest savings, vaccinating all remaining
      workers captured additional savings and, in fact, reduced healthcare workers' and
      critical infrastructure workers' chances of infection. Moreover, although
      employee vaccination compliance affected the epidemic, once 20% compliance was
      achieved, additional increases in compliance provided less incremental benefit.
      Even though a vast majority of the workplaces in the DC metropolitan region had
      fewer than 100 employees, focusing on vaccinating only those in larger firms (>
      or =100 employees) was just as effective in mitigating the epidemic as trying to
      vaccinate employees in all workplaces. CONCLUSIONS: Timely vaccination of at
      least 20% of the large-company workforce can play an important role in epidemic
      mitigation.

PMID- 20042312
TI  - Hypertension, hyperglycemia, and hyperlipemia among adolescents with intellectual
      disabilities.
AB  - The present paper aims to assess the hypertension, hyperglycemia and
      hyperlipidemia prevalence of adolescents with intellectual disabilities, and to
      recognize the health disparities between the study participants and the general
      population. This study conducted a cross-sectional medical chart analysis of 856
      students who participated in school enrolment health examinations in three
      special schools in Taiwan from 2005 to 2007. We found there were 11.7% cases had
      hypertension. The biochemical analyses results showed that the elevated or
      abnormal rates of each exam were the following: triglyceride (9.1%), total
      cholesterol (1.1%), and fasting plasma glucose (0.3%). The study found the
      prevalence of hypertension and elevated triglyceride were significantly higher
      than the general population at the same age, and the body mass index had
      significantly correlated to hypertension and elevated triglyceride tests. Based
      on the study findings, many potential risks for metabolic syndrome in adolescents
      with intellectual disabilities were higher than the general population. The
      present study suggests that it is necessary to monitor and set up a follow-up
      health policy for students with intellectual disabilities in healthcare system.

PMID- 20042313
TI  - Image segmentation by EM-based adaptive pulse coupled neural networks in brain
      magnetic resonance imaging.
AB  - We propose an automatic hybrid image segmentation model that integrates the
      statistical expectation maximization (EM) model and the spatial pulse coupled
      neural network (PCNN) for brain magnetic resonance imaging (MRI) segmentation. In
      addition, an adaptive mechanism is developed to fine tune the PCNN parameters.
      The EM model serves two functions: evaluation of the PCNN image segmentation and
      adaptive adjustment of the PCNN parameters for optimal segmentation. To evaluate
      the performance of the adaptive EM-PCNN, we use it to segment MR brain image into
      gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The
      performance of the adaptive EM-PCNN is compared with that of the non-adaptive EM
      PCNN, EM, and Bias Corrected Fuzzy C-Means (BCFCM) algorithms. The result is four
      sets of boundaries for the GM and the brain parenchyma (GM+WM), the two regions
      of most interest in medical research and clinical applications. Each set of
      boundaries is compared with the golden standard to evaluate the segmentation
      performance. The adaptive EM-PCNN significantly outperforms the non-adaptive EM
      PCNN, EM, and BCFCM algorithms in gray mater segmentation. In brain parenchyma
      segmentation, the adaptive EM-PCNN significantly outperforms the BCFCM only.
      However, the adaptive EM-PCNN is better than the non-adaptive EM-PCNN and EM on
      average. We conclude that of the three approaches, the adaptive EM-PCNN yields
      the best results for gray matter and brain parenchyma segmentation.

PMID- 20042314
TI  - Effects of tobacco smoke on immunity, inflammation and autoimmunity.
AB  - Smoking is a central factor in many pathological conditions. Its role in
      neoplasm, lung and cardiovascular diseases has been well established for years.
      However it is less acknowledged the cigarette smoking affects both the innate and
      adoptive immune arms. Cigarette smoke was shown to augment the production of
      numerous pro-inflammatory cytokines such as TNF-alpha, IL-1, IL-6, IL-8 GM-CSF
      and to decrease the levels of anti-inflammatory cytokines such as IL-10. Tobacco
      smoke via multiple mechanisms leads to elevated IgE concentrations and to the
      subsequent development of atopic diseases and asthma. Cigarette smoke has also
      been shown activate in many ways macrophage and dendritic cell activity. While it
      is better evident how cigarette smoke evokes airway diseases more mechanisms are
      being revealed linking this social hazard to autoimmune disorders, for instance
      via the production of antibodies recognizing citrullinated proteins in rheumatoid
      arthritis or by the elevation of anti-dsDNA titers in systemic lupus
      erythematosus. The current review underlines the importance of smoking prevention
      and eradication not only in respiratory disorders but also in autoimmune
      conditions as well.

PMID- 20042315
TI  - Prevention of thrombosis after microvascular tissue transfer in the head and
      neck. A review of the literature and the state of affairs in Dutch Head and Neck
      Cancer Centers.
AB  - Free vascularized graft or free-flap reconstruction is frequently used in the
      reconstruction of defects in head and neck oncology patients. A common
      complication in free-flap surgery is thrombosis. Thrombosis occurs in 8-14% of
      cases and often leads to flap failure. A review of the literature on this subject
      was carried out and Dutch head and neck cancer centres were asked to share their
      guidelines concerning the prevention of thrombosis after free vascularized graft
      surgery. No consensus in the literature was found on how thrombosis could best be
      prevented. The Dutch Head and Neck Cancer Centers use routine deep venous
      thrombosis prophylaxis to prevent thrombosis in the anastomosis. It was also
      concluded that non-pharmacologic measures for preventing thrombosis, such as
      meticulous microvascular surgery and smoking cessation prior to the operation,
      are thought to play an important role in the prevention of thrombosis in
      microvascular free-flap reconstructions. It has not been determined which pre-
      and postoperative pharmacologic measure can prevent thrombosis most effectively.
      A pharmacologic regimen to prevent thrombosis that is customized to the patient
      is suggested. This should be based on an individual risk profile for the
      development of thrombosis.

PMID- 20042316
TI  - Increased expression of Cathepsin B in oral squamous cell carcinoma.
AB  - Previously, an in vitro cellular carcinogenesis model of oral squamous cell
      carcinoma (OSCC) was established with a line of human immortalized oral
      epithelial cells (HIOECs), a line of cancerous HB96 cells and another type of
      cell (HB56 cells) at the early stage of carcinogenesis. In this study,
      comparative proteomic analysis identified a panel of differentially expressed
      proteins among these cells. Cathepsin B was one of the significantly up-regulated
      proteins accompanying cellular transformation. Cathepsin B was further validated
      for its expression in the three cell lines and in clinical samples of tumour
      tissues and their adjacent normal epithelia from 30 primary OSCC patients.
      Western blot analysis and real-time PCR detected increased Cathepsin B protein
      and mRNA levels in the cancerous HB56 and HB96 cells over HIOECs.
      Immunohistochemistry and real-time PCR showed elevated Cathepsin B protein and
      mRNA levels in the tumour tissues over the adjacent non-malignant epithelia from
      OSCC patients. The results presented here suggest that the expression of
      Cathepsin B increases along with the cancerisation in OSCC both in vitro and in
      vivo, and it may serve as a candidate biomarker of OSCC.

PMID- 20042317
TI  - Changes in nasal structures following orthopaedic and surgically assisted rapid
      maxillary expansion.
AB  - The aim of this study was to investigate and compare changes in the nasomaxillary
      complex substructures following orthopaedic rapid maxillary expansion (RME) and
      surgically assisted RME (SARME). 10 patients received RME, 10 patients received
      SARME, and 10 patients served as an untreated control group. Lateral and
      posteroanterior cephalograms were obtained for each individual at pre
      expansion/pre-control (T1) and post-expansion/post-control (T2). Descriptive
      parameters and transversal measurements on maxillo-mandibular dentoalveolar
      structures and skeletal bases, right and left nasal cavity angles (NC/Lom/VL and
      CN/Lom/VL, respectively), total nasal cavity angle (NC/Lom/CN), nasal cavity
      width (NC-CN) and nasal septum angle (sn/Lom/VL) were also calculated. Paired t
      tests were used to evaluate changes within groups following treatment/control.
      Analysis of variance (ANOVA) and Duncan's tests were used to compare changes
      between groups. With the exception of nasal septum deviation, all nasal
      parameters significantly increased following RME and SARME. The increases in the
      SARME group were greater than in the other groups, but no statistically
      significant differences were recorded between the RME and SARME groups. Neither
      RME nor SARME created positional changes in the nasal septum.

PMID- 20042318
TI  - (+)-UH 232, a partial agonist of the D3 dopamine receptors, attenuates cognitive
      effects of angiotensin IV and des-Phe(6)-angiotensin IV in rats.
AB  - We have recently found that postsynaptic D3 dopamine (DA) receptors appear not to
      participate in the memory enhancing effects of the angiotensin AT4 receptor
      agonists angiotensin IV (Ang IV) and des-Phe(6)-Ang IV. In this study we
      evaluated role of the presynaptic DA D3 receptors in these effects. For that
      purpose effect of (+)-UH 232, a selective D3 DA receptors partial agonist
      preferring presynaptic sites, on the pro-cognitive action of
      intracerebroventricularly (icv) injected Ang IV and des-Phe(6)-Ang IV was
      examined. Male Wistar rats weighing 180-200 g were used. Both peptides given at
      the dose of 1 nmol facilitated recall of a passive avoidance (PA) behaviour,
      improved object recognition (OR), and increased apomorphine-induced stereotype
      behaviour. In the auxiliary tests performed to control for the unspecific
      influence of motor (open field, OF) and emotional ('plus' maze, PM) effects of
      our treatments on the results of the memory tests they had either no (OF) or
      negligible (PM) effects. Intraperitoneal pre-treatment of the animals with an
      ineffective on its own dose (1 mg/kg) of (+)-UH 232 abolished or markedly
      diminished effects of both peptides on PA and OR but did not influence
      enhancement of stereotypy caused by the peptides.

PMID- 20042319
TI  - PEI grafted hyperbranched polymers with polyglycerol as a core for gene delivery.
AB  - Hyperbranched polymers, PG6-PEI25k and PG6-PEI800, were synthesized through
      grafting branched polyethylenimines (PEIs) with molecular weights of 25 kDa and
      800 Da to a polyglycerol core (PG6), respectively. The structure of the polymers
      was characterized by 1H NMR and FTIR. Through agarose gel electrophoresis
      retardation assay, PG6-PEI25k and PG6-PEI800 were demonstrated to have capability
      for DNA binding. PG6-PEI/DNA complexes with different weight ratios were
      characterized by TEM and particle size analysis. The activity of PG6-PEIs to
      mediate transfection of reporter plasmids pEGFP-C1 and pGL3-Luc was evaluated on
      293T and HeLa cell lines. PG6-PEI25k and PG6-PEI800 showed enhanced levels in
      transgene expression and decreased cytotoxicities as compared with PEI25k and
      PEI800, respectively. The results indicated potential applications of PG6-PEIs
      for efficient gene delivery.

PMID- 20042320
TI  - Study of surfactant combinations and development of a novel nanoemulsion for
      minimising variations in bioavailability of ezetimibe.
AB  - The present study aimed at developing an optimal nanoemulsion of ezetimibe and
      evaluating its stability, pharmacodynamic and pharmacokinetic potential.
      Solubility of ezetimibe was determined in various vehicles. Surfactants and
      cosurfactants were grouped in two different combinations to construct
      pseudoternary phase diagrams. Formulations were selected from the o/w
      nanoemulsion region and were subjected to various thermodynamic stability and
      dispersibility tests. Optimized formulations were characterized for their
      percentage transmittance, refractive index, viscosity, droplet size and zeta
      potential. Release rate of optimized formulations was determined using an in
      vitro dissolution test. The formulation used for assessment of lipid lowering
      potential and bioavailability contained Capryol 90 (10%, v/v), Tween 20 (33.33%,
      v/v), PEG 400 (16.67%, v/v), double distilled water (40%, v/v). The release of
      drug from the nanoemulsion formulations was extremely significant (p<0.001) in
      comparison to the drug suspension. More than 60% of the drug was released in the
      initial 1h of the dissolution study in comparison to the drug suspension. The
      value of total cholesterol in the group administered with the formulation PF1 was
      highly significant (p<0.001) with respect to the group administered with the
      suspension of the drug. The plasma concentration time profile of ezetimibe from
      nanoemulsion represented greater improvement of drug absorption than the marketed
      formulation and simple drug suspension. The shelf life of the nanoemulsion was
      found to be 5.94 years at room temperature. The present study established
      nanoemulsion formulation to be one of the possible alternatives to traditional
      oral formulations of ezetimibe to improve its bioavailability.

PMID- 20042321
TI  - Activity modulation and reusability of beta-D-galactosidase confined in sol-gel
      derived porous silicate glass.
AB  - In the present work we applied the sol-gel method to obtain glass lentils
      entrapping beta-D-galactosidase (beta-Gal) (Ebeta-Gal) within a silicate matrix.
      The effect of pH, temperature, polarity and salt concentration on the activity of
      Ebeta-Gal was studied. Apparent kinetic parameters for ortho-nitro-phenyl-beta-D
      galactopyranoside hydrolysis catalyzed by Ebeta-Gal (V'max, K'M) were lower
      compared to the soluble enzyme (Sbeta-Gal), reflecting the solute diffusion
      restriction imposed by the matrix observed in the time curves, a partial protein
      inactivation upon encapsulation, and an improvement in the affinity of Ebeta-Gal
      for the substrate as compared with Sbeta-Gal. At pH<4, Ebeta-Gal stability was
      higher than that of Sbeta-Gal. Ebeta-Gal could be reused after storage at 4
      degrees C for up to 90 days, and retained its activity profile within the range
      of pH=2-10 and saline concentration 0-400 mM. Pre-incubation at 75 degrees C for
      30 min fully inactivated Sbeta-Gal while Ebeta-Gal retained approximately 90% of
      its activity, even in the reused samples. Encapsulation did not introduce
      additional impairments to the reaction rate measured in heterogeneous
      dispersions, beyond those derived from their own particle-crowded environment.
      This reusable Ebeta-Gal was resistant to typical technological conditions applied
      in milk processing that would lead to the unfolding and inactivation of Sbeta
      Gal. The results are discussed from the biophysical viewpoint.

PMID- 20042322
TI  - Osthol regulates hepatic PPAR alpha-mediated lipogenic gene expression in
      alcoholic fatty liver murine.
AB  - Our previous studies found that osthol, an active constituent isolated from
      Cnidium monnieri (L.) Cusson (Apiaceae), could ameliorate the accumulation of
      lipids and decrease the lipid levels in serum and hepatic tissue in alcohol
      induced fatty liver mice and rats. The objective of this study was to investigate
      its possible mechanism of the lipid-lowering effect. A mouse model with alcoholic
      fatty liver was induced by orally feeding 52% erguotou wine by gavage when they
      were simultaneously treated with osthol 10, 20, 40 mg/kg for 4 weeks. The BRL
      cells (rat hepatocyte line) were cultured and treated with osthol at 25, 50, 100,
      200 microg/ml for 24h. The mRNA expressions of peroxisome proliferator-activated
      receptor (PPAR) alpha, diacylglycerol acyltransferase (DGAT), 3-hydroxy-3
      methylglutaryl-CoA (HMG-CoA) reductase and cholesterol 7 alpha-hydroxylase
      (CYP7A) in mouse hepatic tissue or cultured hepatocytes were determined by
      reverse transcription polymerase chain reaction (RT-PCR). After treatment with
      osthol, the PPAR alpha mRNA expression in mouse liver and cultured hepatocytes
      was increased in dose dependent manner, while its related target genes for mRNA
      expression, e.g., DGAT and HMG-CoA reductase, were decreased, the CYP7A was
      inversely increased. And osthol-regulated mRNA expressions of DGAT, HMG-CoA
      reductase and CYP7A in the cultured hepatocytes were abrogated after pretreatment
      with specific inhibitor of PPAR alpha, MK886. It was concluded that osthol might
      regulate the gene expressions of DGAT, HMG-CoA reductase and CYP7A via increasing
      the PPAR alpha mRNA expression.

PMID- 20042323
TI  - Valeriana officinalis root extracts have potent anxiolytic effects in laboratory
      rats.
AB  - Valerian root (Valeriana officinalis) is a popular and widely available herbal
      supplement, primarily used to treat insomnia and anxiety. Until recently, its
      mechanism of action has remained unknown. Neurobiological research has begun to
      show that the herb, with its active valerenic acid, interacts with the GABA(A)
      ergic system, a mechanism of action similar to the benzodiazepine drugs. This
      series of experiments sought to corroborate these findings with behavioral
      measures, compare them to the benzodiazepine diazepam, and to analyze the
      chemical composition of Valeriana officinalis. Rats were administered either
      ethanol (1 ml/kg), diazepam (1mg/kg), valerian root extract (3 ml/kg), valerenic
      acid (3mg/kg), or a solution of valerenic acid and exogenous GABA (75 microg/kg
      and 3.6 microg/kg, respectively) and assessed for the number of entries and time
      spent on the open arms of an elevated plus maze. Results showed that there was a
      significant reduction in anxious behavior when valerian extract or valerenic acid
      exposed subjects were compared to the ethanol control group. The evidence
      supports Valeriana officinalis as a potential alternative to the traditional
      anxiolytics as measured by the elevated plus maze.

PMID- 20042324
TI  - Ecotoxicity of wastes in avoidance tests with Enchytraeus albidus, Enchytraeus
      crypticus and Eisenia fetida (Oligochaeta).
AB  - Contact bioassays are important for testing the ecotoxicity of solid materials.
      However, survival and reproduction tests are often not practical due to their
      duration which may last for several weeks. Avoidance tests with soil
      invertebrates may offer an alternative or extension to the classic test batteries
      due to their short duration (days rather than weeks) and due to a sensitive sub
      acute endpoint (behavior). THE AIMS OF OUR STUDY WERE: (a) to evaluate the
      effects of three solid industrial wastes (incineration ash, contaminated wood
      chips and contaminated soil) on three Oligochaeta species (enchytraeids
      Enchytraeusalbidus, Enchytraeus crypticus and earthworm Eisenia fetida) in
      avoidance tests; (b) to compare the sensitivity among the species and to compare
      results of avoidance test to reproduction tests; (c) to elucidate if measuring
      the weight in the earthworm avoidance test could be reasonable additional
      endpoint. Avoidance mostly increased with the increasing percent of waste in the
      mixture showing a dose-response curve. E. fetida was the most sensitive species
      and E. crypticus the least one. An additional endpoint, (changes in weight after
      two-day exposure) was not found to be more sensitive than avoidance reaction, but
      it confirmed that earthworms staying in the highest concentrations of the waste
      mixture were affected showing apparent weight reduction. Our results indicate
      that avoidance tests with earthworms and enchytraeids are feasible for waste
      testing.

PMID- 20042325
TI  - Seasonal generation and composition of garden waste in Aarhus (Denmark).
AB  - Garden waste generation and composition were studied in Aarhus, Denmark. The
      amount of garden waste generated varied seasonally, from 2.5kgperson(-1)month(-1)
      in winter to 19.4kgperson(-1)month(-1) in summer. Seasonal fractional composition
      and chemical characterization of garden waste were determined by sorting and
      sampling garden waste eight times during 1year. On a yearly basis, the major
      fraction of garden waste was "small stuff" (flowers, grass clippings, hedge
      cuttings and soil) making up more than 90% (wet waste distribution) during the
      summer. The woody fractions (branches, wood) are more significant during the
      winter. Seasonal trends in waste chemical composition were recorded and an
      average annual composition of garden waste was calculated, considering the
      varying monthly generation and material fraction composition: the wet garden
      waste contained 40% water, 30% organic matter (VS) and 30% ash. The ash content
      suggests that the garden waste contains a significant amount of soil. This is in
      particular the case during summer. Of nutrients, the garden waste contained in
      average on a dry matter basis 0.6% N, 0.1% P, and 1.0% K. However, the contents
      varied significantly among the fractions and during the year. The content of
      trace elements (Cd, Cr, Cu, Hg, Ni, Pb, and Zn) was low.

PMID- 20042327
TI  - Palm oil mill effluent treatment using a two-stage microbial fuel cells system
      integrated with immobilized biological aerated filters.
AB  - An integrated system of two-stage microbial fuel cells (MFCs) and immobilized
      biological aerated filters (I-BAFs) was used to treat palm oil mill effluent
      (POME) at laboratory scale. By replacing the conventional two-stage up-flow
      anaerobic sludge blanket (UASB) with a newly proposed upflow membrane-less
      microbial fuel cell (UML-MFC) in the integrated system, significant improvements
      on NH(3)-N removal were observed and direct electricity generation implemented in
      both MFC1 and MFC2. Moreover, the coupled iron-carbon micro-electrolysis in the
      cathode of MFC2 further enhanced treatment efficiency of organic compounds. The I
      BAFs played a major role in further removal of NH(3)-N and COD. For influent COD
      and NH(3)-N of 10,000 and 125 mg/L, respectively, the final effluents COD and
      NH(3)-N were below 350 and 8 mg/L, with removal rates higher than 96.5% and
      93.6%. The GC-MS analysis indicated that most of the contaminants were
      satisfactorily biodegraded by the integrated system.

PMID- 20042328
TI  - Temperature-phased anaerobic digestion (TPAD) to obtain class A biosolids: a semi
      continuous study.
AB  - Regulations regarding the land application of sewage sludge require the
      performance of highly efficient treatments for pathogen reduction, such as
      temperature-phased anaerobic digestion (TPAD). Several semi-continuous
      experiments with different solid residence times (SRTs) have been made to find
      the best combination - TPAD 15/15, TPAD 5/15, TPAD 3/15 or TPAD 3/12. TPAD
      systems showed better performance in terms of VS destruction, gas production,
      sludge dewaterability, and process stability at total SRT of 15 days, compared
      with single-stage mesophilic or thermophilic digestion at the same SRT. Average
      VS reductions (VSR) using the overall TPAD 5/15 (78%), TPAD 3/15 (87%), and TPAD
      3/12 (87%) were significantly higher than mesophilic control operating with an
      SRT of 15 days (40% VSR). The best results were obtained for TPAD 3/15 with 0.62
      LCH(4) g(-1) VS(r), faecal coliform 10(3) MPN/g TS, and Salmonella spp. 1 MPN/4 g
      TS. Although both TPAD 3/15 and TPAD 3/12 were efficient enough to obtain Class A
      biosolids.

PMID- 20042326
TI  - Emerging synergy between nanotechnology and implantable biosensors: a review.
AB  - The development of implantable biosensors for continuous monitoring of
      metabolites is an area of sustained scientific and technological interests. On
      the other hand, nanotechnology, a discipline which deals with the properties of
      materials at the nanoscale, is developing as a potent tool to enhance the
      performance of these biosensors. This article reviews the current state of
      implantable biosensors, highlighting the synergy between nanotechnology and
      sensor performance. Emphasis is placed on the electrochemical method of detection
      in light of its widespread usage and substantial nanotechnology based
      improvements in various aspects of electrochemical biosensor performance.
      Finally, issues regarding toxicity and biocompatibility of nanomaterials, along
      with future prospects for the application of nanotechnology in implantable
      biosensors, are discussed.

PMID- 20042329
TI  - Pretreatment technologies for an efficient bioethanol production process based on
      enzymatic hydrolysis: A review.
AB  - Biofuel produced from lignocellulosic materials, so-called second generation
      bioethanol shows energetic, economic and environmental advantages in comparison
      to bioethanol from starch or sugar. However, physical and chemical barriers
      caused by the close association of the main components of lignocellulosic
      biomass, hinder the hydrolysis of cellulose and hemicellulose to fermentable
      sugars. The main goal of pretreatment is to increase the enzyme accessibility
      improving digestibility of cellulose. Each pretreatment has a specific effect on
      the cellulose, hemicellulose and lignin fraction thus, different pretreatment
      methods and conditions should be chosen according to the process configuration
      selected for the subsequent hydrolysis and fermentation steps. This paper reviews
      the most interesting technologies for ethanol production from lignocellulose and
      it points out several key properties that should be targeted for low-cost and
      advanced pretreatment processes.

PMID- 20042330
TI  - Production of probiotic biomass (Lactobacillus casei) in goat milk whey:
      comparison of batch, continuous and fed-batch cultures.
AB  - This contribution examines the technical feasibility of producing high added
      value probiotic biomass from deproteinized and non-supplemented milk whey. The
      kinetics of growth of Lactobacillus casei in deproteinized goat milk whey was
      analyzed. Experiments in batch, continuous and fed-batch conditions were
      conducted in a 3 L fully instrumented bioreactor. Final substrate and biomass
      concentrations, yields and productivities are reported for different culture
      strategies. A kinetic analysis was conducted to characterize biomass production,
      product inhibition effects, and substrate consumption rates. Due to the strong
      product inhibition, fed-batch cultures at high biomass concentration rendered
      higher productivity (0.45 g L(-1) h(-1)) than batch and continuous cultures (0.11
      g L(-1) h(-1)), complete lactose conversions (<1.0 g of lactose/L at the end of
      each fed-batch cycle), and a product with higher viable cell counts (2 x 10(10)
      cell/g of freeze-dried product). Based on our result, high-cell density fed-batch
      strategies are recommended for commercial production of probiotic L. casei
      biomass.

PMID- 20042331
TI  - Semi-dry mesophilic anaerobic digestion of water sorted organic fraction of
      municipal solid waste (WS-OFMSW).
AB  - An innovative municipal solid waste separation technology - water separation was
      developed in China recently. The purpose of this study was to evaluate the
      feasibility of anaerobic digestion from water sorted organic fraction of
      municipal solid waste (WS-OFMSW) to methane. A group of bench-scale (35 L)
      mesophilic (30 + or - 2 degrees Celsius) batch anaerobic digestions were carried
      out with three total solids in reactor (TSr = 16.0%, 13.5% and 11.0%). The
      biodegradability of WS-OFMSW with VS/TS of 61.6% was better than that of
      mechanically sorted OFMSW but still poor than that of source sorted OFMSW. No
      inhibitions of metal ions, volatile fatty acids and ammonia on anaerobic
      digestion were found. The reactors with TSr 16.0%, 13.5% and 11.0% achieved
      methane yield of 273, 283 and 314 L/kgVS and VS removal rate of 26.1%, 35.8% and
      41.8%, respectively. The average methane content in biogas was about 66% for all
      reactors.

PMID- 20042332
TI  - Lime pretreatment of switchgrass at mild temperatures for ethanol production.
AB  - To improve the enzymatic digestibility of switchgrass at mild temperatures, lime
      pretreatment of switchgrass was explored at 50 and 21 degrees Celsius, and
      compared with that at 121 degrees Celsius. The effects of residence time, lime
      loading, and biomass washing on the sugar production efficiency were
      investigated. Pretreatments were evaluated based on the yields of biomass-derived
      sugars in the subsequent enzymatic hydrolysis. Under the best pretreatment
      conditions (50 degrees Celsius, 24 h, 0.10 g Ca(OH)(2)/g raw biomass, and wash
      intensity of 100 ml water/g raw biomass), the yields of glucose, xylose, and
      total reducing sugars reached 239.6, 127.2, and 433.4 mg/g raw biomass, which
      were respectively 3.15, 5.78, and 3.61 times those of untreated biomass. The
      study on calcium-lignin bonding showed that calcium ions crosslinked lignin
      molecules under alkaline conditions, which substantially decreased lignin
      solubilization during pretreatment, but the resulting high lignin contents of the
      pretreated biomass did not compromise the improvement of enzymatic digestibility.

PMID- 20042333
TI  - Benzimidazole- and indole-substituted 1,3'-bipyrrolidine benzamides as histamine
      H3 receptor antagonists.
AB  - Using a focused screen of biogenic amine compounds we identified a novel series
      of H(3)R antagonists. A preliminary SAR study led to reduction of MW while
      increasing binding affinity and potency. Optimization of the physical properties
      of the series led to (S)-6n, with improved brain to plasma exposure and efficacy
      in both water intake and novel object recognition models.

PMID- 20042334
TI  - Discovery and SAR of small molecule PAR1 antagonists.
AB  - High-throughput screening resulted in the identification of a small molecule
      inhibitor of PAR1. Optimisation of the initial hit led to the discovery of
      compounds 34 and 49, which displayed antithrombotic activity in an arteriovenous
      shunt model in the rat after iv administration.

PMID- 20042335
TI  - [Lys(DOTA)4]BVD15, a novel and potent neuropeptide Y analog designed for Y1
      receptor-targeted breast tumor imaging.
AB  - We substituted a truncated neuropeptide Y (NPY) analog, [Pro(30), Tyr(32),
      Leu(34)]NPY(28-36)NH(2) also called BVD15, at various positions with DOTA
      (1,4,7,10-tetraazacyclododecane-1,4,7-10-tetraacetic acid) and evaluated the
      effect of the coupling position with the binding affinity for NPY Y(1) receptors
      (NPY1R). Our data suggest that [Lys(DOTA)(4)]BVD15 (K(i)=63+/-25 nM vs. K(i)=39+/
      34 nM for BVD15) is a potent NPY analog suitable for radiolabeling with metallo
      positron emitters for PET imaging of breast cancer.

PMID- 20042336
TI  - The course of anxiety and depression over 5 years of follow-up and risk factors
      in women with early breast cancer: results from the UK Standardisation of
      Radiotherapy Trials (START).
AB  - Prospective data are limited on the course of anxiety and depression and their
      determinants in women with early breast cancer. These parameters were assessed
      before adjuvant radiotherapy (RT) and over 5 years follow-up. Of 2208 women
      recruited to the START QOL study, 35% reported clinically relevant levels of
      anxiety and/or depression pre-RT; there was no significant change in these
      proportions over time. However, 75% women with high baseline anxiety recorded
      further high scores over time whilst one in six had high scores at every follow
      up point. Depression showed a similar pattern with lower frequencies at all time
      points; very few with initial normal scores developed clinically relevant anxiety
      or depression over time. Lower educational level predicted worse anxiety and
      depression over time; younger age predicted worse anxiety and chemotherapy
      predicted worse depression. Scores in the borderline or case range for anxiety or
      depression at baseline were both significantly associated with worse mood states
      over 5 years. These findings indicate the course of anxiety and depression in
      women with specific risk factors. This subgroup of patients requires greater
      clinical attention.

PMID- 20042337
TI  - Experimental models of traumatic axonal injury.
AB  - Traumatic brain injury (TBI) is one of the leading causes of death in people
      under 45 years of age worldwide. Such injury is characterized by a wide spectrum
      of mechanisms of injury and pathologies. Traumatic axonal injury (TAI),
      originally described as diffuse axonal injury, is one of the most common
      pathological features of TBI and is thought to be responsible for the long
      lasting neurological impairments following TBI. Since the late 1980s a series of
      in vivo and in vitro experimental models of TAI have been developed to better
      understand the complex mechanisms of axonal injury and to define the relationship
      between mechanical forces and the structural and functional changes of injured
      axons. These models are designed to mimic as closely as possible the clinical
      condition of human TAI and have greatly improved our understanding of different
      aspects of TAI. The present review summarizes the most widely used experimental
      models of TAI. Focusing in particular on in vivo models, this survey aims to
      provide a broad overview of current knowledge and controversies in the
      development and use of the experimental models of TAI.

PMID- 20042338
TI  - Oligodendroglioma presenting with intradural spinal metastases: an unusual cause
      of cauda equina syndrome.
AB  - We report a 37-year-old man with a primary intracranial oligodendroglioma
      presenting later with symptomatic multiple cerebrospinal fluid (CSF) intradural
      drop spinal metastases. This patient initially presented in 2006 with complex
      partial seizures. Initial histology demonstrated World Health Organization (WHO)
      grade 2 oligodendroglioma. The patient had further generalised seizures 7 months
      after initial tumour resection. MRI at that time confirmed tumour recurrence. The
      patient underwent a repeat craniotomy. Histology showed anaplastic transformation
      to a WHO grade 3 oligodendroglioma. About 30 months after his initial
      presentation, the patient developed a focal neurological deficit in the left leg
      with associated retention of urine. MRI of the neuraxis demonstrated widespread
      leptomeningeal metastatic drop deposits within the spinal canal. We discuss the
      mechanisms involved in tumour dissemination throughout the CSF. We also review
      the relevant literature regarding this phenomenon.

PMID- 20042339
TI  - Synthesis and disulfide bond connectivity-activity studies of a kalata B1
      inspired cyclopeptide against dengue NS2B-NS3 protease.
AB  - Kalata B1 is a plant protein with remarkable thermal, chemical and enzymatic
      stability. Its potential applications could be centered on the possibility of
      using its cyclic structure and cystine knot motif as a scaffold for the design of
      stable pharmaceuticals. To discover potent dengue NS2B-NS3 protease inhibitors,
      we have prepared various kalata B1 analogues by varying the amino acid sequence.
      Mass spectrometric and biochemical investigations of these analogues revealed a
      cyclopeptide whose two fully oxidized forms are substrate-competitive inhibitors
      of the dengue viral NS2B-NS3 protease. Both oxidized forms showed potent
      inhibition with K(i) of 1.39+/-0.35 and 3.03+/-0.75 microM, respectively.

PMID- 20042340
TI  - In situ TEM studies of oxygen vacancy migration for electrically induced
      resistance change effect in cerium oxides.
AB  - Oxide materials with resistance hysteresis are very promising for next generation
      memory devices. However, the microscopic dynamic process of the resistance change
      is still elusive. Here, we use in situ transmission electron microscopy method to
      study the role of oxygen vacancies for the resistance switching effect in cerium
      oxides. The structure change during oxygen vacancy migration in CeO(2) induced by
      electric field was in situ imaged inside high-resolution transmission electron
      microscope, which gives a direct evidence for oxygen migration mechanism for the
      microscopic origin of resistance change effect in CeO(2). Our results have
      implications for understanding the nature of resistance change in metal oxides
      with mixed valence cations, such as fluorite, rutile and perovskite oxides.

PMID- 20042341
TI  - Americium behaviour in plastic vessels.
AB  - The adsorption of (241)Am dissolved in water in different plastic storage vessels
      was determined. Three different plastics were investigated with natural and
      distilled waters and the retention of (241)Am by these plastics was studied. The
      same was done by varying vessel agitation time, vessel agitation speed,
      surface/volume ratio of water in the vessels and water pH. Adsorptions were
      measured to be between 0% and 70%. The adsorption of (241)Am is minimized with no
      water agitation, with PET or PVC plastics, and by water acidification.

PMID- 20042342
TI  - Effect of silica fume addition on the PGNAA measurement of chlorine in concrete.
AB  - Pozzolanic materials, such as fly ash (FA), silica fume (SF), and blast furnace
      slag (BFS) are added to Portland cement in concrete to prevent reinforcement
      steel corrosion in concrete. Further preventive measure against reinforcement
      steel corrosion require monitoring of chloride salts concentration in concrete
      using non-destructive techniques, such as the prompt gamma-ray neutron activation
      analysis (PGNAA) technique. Due to interferences between gamma-rays from chlorine
      and calcium in PGNAA technique, detection limit of chlorine in concrete strongly
      depends upon calcium concentration in concrete. SF mainly contains silica and its
      addition to cement concrete reduces overall concentration of calcium in concrete.
      This may result in an improvement in detection limit of chlorine in SF-based
      concrete in PGNAA studies. Particularly for chlorine detection using 6.11 and
      6.62 MeV prompt gamma-rays that strongly interfere with 6.42 MeV prompt gamma
      rays from calcium. In this study, SF was added to Portland cement to prevent
      concrete reinforcement steel from corrosion. The chlorine concentration in SF
      cement concrete specimens containing 0.2-3.0 wt% chlorine was measured through
      yield of 1.16, 1.95, 6.11, 6.62, 7.41, 7.79, and 8.58 MeV chlorine gamma-rays
      using PGNAA technique. An excellent agreement was noted between the experimental
      yield of the prompt gamma-rays and the gamma-ray yield calculated through the
      Monte Carlo simulations. Further the minimum detectable concentration (MDC) of
      chlorine in SF cement concrete was calculated and compared with the MDC values of
      chlorine in plain concrete and concrete mixed with fly ash cement. The MDC of
      chlorine in SF-based concrete through 6.11 MeV, and 6.62 MeV chlorine gamma-rays
      was found to be improved as compared to those in plain concrete and concrete
      mixed with fly ash cement.

PMID- 20042344
TI  - From green to red--To more dead? Autofluorescent proteins as photosensitizers.
AB  - Inactive compounds like autofluorescent proteins can absorb visible daylight
      (around 500-700 nm) and can emit active electrons producing reactive oxygen
      species (ROS) leading to an increase in photokilling processes in bacteria. The
      endogenously originated ROS create single strand breaks in the cells DNA. These
      various types of breaks can be partially repaired by different cellular repair
      systems but a high number of breaks leads to cell death. A dramatic increase in
      cell killing can be observed from green, via yellow to red color emission. This
      was tested by colony forming ability. The generation of ROS and the bacterial
      protection mechanisms are discussed. We outline some possibilities for use the
      protein's properties for treatment of antibiotic multi-resistant and difficult to
      treat bacteria like the methicillin-resistant Staphylococcus aureus (MRSA).

PMID- 20042343
TI  - Primary standardization of 57Co.
AB  - This work describes the method developed by the Nuclear Metrology Laboratory in
      IPEN, Sao Paulo, Brazil, for the standardization of a (57)Co radioactive
      solution. Cobalt-57 is a radionuclide used for calibrating gamma-ray and X-ray
      spectrometers, as well as a gamma reference source for dose calibrators used in
      nuclear medicine services. Two 4pibeta-gamma coincidence systems were used to
      perform the standardization, the first used a 4pi(PC) counter coupled to a pair
      of 76 mm x 76 mm NaI(Tl) scintillators for detecting gamma-rays, the other one
      used a HPGe spectrometer for gamma detection. The measurements were performed by
      selecting a gamma-ray window comprising the (122 keV+136 keV) total absorption
      energy peaks in the NaI(Tl) and selecting the total absorption peak of 122 keV in
      the germanium detector. The electronic system used the TAC method developed at
      LMN for registering the observed events. The methodology recently developed by
      the LMN for simulating all detection processes in a 4pibeta-gamma coincidence
      system, by means of the Monte Carlo technique, was applied and the behavior of
      extrapolation curve compared to experimental data. The final activity obtained by
      the Monte Carlo calculation agrees with the experimental results within the
      experimental uncertainty.

PMID- 20042345
TI  - Proteomic evaluation and location of UVB-induced photo-oxidation in wool.
AB  - Photo-oxidation of proteinaceous fibres correlates directly to lowered appearance
      retention and performance, with particular commercial significance for wool and
      human hair. We here outline the first detailed proteomic evaluation of
      differential photo-oxidation occurring in the cuticle and cortex of wool fibres.
      After exposure of whole wool to UVB irradiation, physical disruption techniques
      designed to minimise further oxidative modification were utilised to prepare
      enriched cuticle and cortex fractions. This was followed by comprehensive redox
      proteomic analyses of photo-oxidation via the location within the fibre
      components of modifications to aromatic residues. An oxidative classification
      system was developed and applied to provide further insight into differential
      photo-oxidation. These results were compared with coloration changes observed
      within the cuticular and cortical components of the fibre. In this study,
      although the cuticle was observed to have a higher level of baseline oxidation,
      the cortex exhibited significantly higher levels of photo-oxidation under UVB
      irradiation. These proteomic results were supported by the observation of
      significantly higher photoyellowing within the cortex than within the cuticle. It
      has been assumed that fibre photo-oxidation was predominantly confined to the
      wool cuticle, and that changes within the cuticle had the greatest effect on
      appearance retention. These results provide new insight into the contribution of
      the cortex to photo-induced discoloration of proteinaceous animal fibres.

PMID- 20042347
TI  - Varying susceptibility of pulmonary cytokine production to lipopolysaccharide in
      mice.
AB  - OBJECTIVES: The lipopolysaccharide (LPS)-induced acute lung injury (ALI) model
      has been widely applied for pathophysiological and pharmacological research. The
      aim of present study is to understand the variation of acute pulmonary
      inflammation between mouse strains. METHODS: The present study investigated the
      susceptibility of acute production of inflammatory mediators, e.g. cytokines,
      chemokines and others, to LPS in C57BL/6J, Balb/cJ, DBA/1J, CD-1, NMRI, DBA/2J,
      A/J, and C3H/HeN mice. RESULTS: The susceptibility to intra-tracheal challenge
      with LPS varied between measured variables, durations and strains. General lung
      hyper-reactive susceptibility to LPS-induced pulmonary production of 6-8
      inflammatory mediators followed the order NMRI, Balb/cJ, C3H/HeN, A/J, C57BL/6J,
      DBA/1J, DBA/2J and CD-1 mice at 4h, and A/J, C3H/HeN, CD-1, NMRI, C57BL/6J,
      Balb/cJ, DBA/2J and DBA/1J mice at 24h. CONCLUSIONS: Our data provide information
      for scientists to consider the proper strain of mice for the measurement of
      specific inflammatory mediators and to select sensitive or resistant mouse
      strains for understanding genetic variation in the pathogenesis and for the
      screening of target-oriented drug development.

PMID- 20042346
TI  - First-line single-agent cetuximab in elderly patients with metastatic colorectal
      cancer. A phase II clinical and molecular study of the Spanish group for
      digestive tumor therapy (TTD).
AB  - PURPOSE: to evaluate the efficacy and safety of first-line single-agent cetuximab
      in fit elderly patients with metastatic colorectal cancer, as well as potential
      molecular predictive factors for efficacy. PATIENTS AND METHODS: patients aged 70
      or older with metastatic CRC without criteria for frailty and no prior treatment
      for advanced disease were treated with single-agent cetuximab 400mg/m(2) followed
      by weekly 250mg/m(2) until disease progression or unacceptable toxicity. RESULTS:
      forty-one patients were included. Two patients achieved a complete response and 4
      patients had a partial response for an overall response rate of 14.6%. Fifteen
      patients (36.6%) remained stable. Median time to progression was 2.9 months and
      median overall survival 11.1 months despite two-third of patients received
      chemotherapy at progression. Forty-five percent of EGFR gene copy number positive
      patients by FISH were progression-free at 12 weeks, in contrast with 12% of FISH
      negative patients (p=0.04). Grade 3 skin toxicity was reported in 5 patients
      (12.2%). Hypersensitivity infusion reactions were not reported and there were no
      toxic deaths. CONCLUSION: cetuximab is a safe monoclonal antibody with moderate
      activity in first-line metastatic colorectal cancer, but the present study does
      not support the use of cetuximab as single-agent in first-line fit elderly
      patients with metastatic CRC.

PMID- 20042348
TI  - International Association for Biologicals Symposium: "Advances in Transfusion
      Safety", Cambridge, UK. Foreword.

PMID- 20042349
TI  - Quadriceps EMG frequency content following isometric lumbar extension exercise.
AB  - A relationship exists between muscles of the lumbar spine and those of the lower
      extremity where the quadriceps become more inhibited after lumbar paraspinal. The
      purpose of this experiment was to compare surface electromyography (sEMG) total
      frequency content after lumbar paraspinal fatiguing exercise. SCOPE: 50 subjects
      performed fatiguing lumbar extension exercise indexed by downward shifts in
      median frequency calculated from lumbar paraspinal sEMG signal. Before and after
      each exercise set we recorded maximal, isometric knee extension torque and
      quadriceps central activation ratio (QI) using the superimposed burst technique
      while recording vastus lateralis sEMG. We calculated total frequency content of
      the sEMG signal (fEMG(TOTAL)) as the area of the quadriceps sEMG frequency
      spectrum. Quadriceps fEMG(TOTAL) decreased from baseline following the first and
      second exercise sets. There was no significant change in quadriceps sEMG median
      frequency among baseline and post-exercise measures. The change in fEMG(TOTAL)
      was correlated with the change in QI following the first (r=-0.41, P=0.003) and
      second (r=-0.32, P=0.02) exercise sets. CONCLUSION: Quadriceps fEMG(TOTAL)
      decreased following fatiguing lumbar extension exercise, in the absence of a
      significant change in quadriceps median frequency.

PMID- 20042350
TI  - Preoperative and intraoperative sonographic visibility of collagen-based breast
      biopsy marker clips.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to determine the sonographic
      visibility of implanted collagen-based breast biopsy marker clips in the clinic
      and operating room. MATERIALS AND METHODS: Female patients aged > or =18 years
      who presented for preoperative surgical evaluation within 4 weeks of ultrasound
      guided breast biopsy and collagen-based marker clip placement were eligible for
      this pilot study. The sonographic visibility of the marker clips was rated from 1
      (not visible) to 5 (clearly visible) by surgeons at the preoperative appointment,
      by radiologists at wire localization, and by surgeons in the operating room.
      Visibility was considered inadequate for values of 1 or 2 and adequate for values
      of 3, 4, or 5. The data were compared using Wilcoxon's signed-rank test for
      paired differences across physician (radiologist vs surgeon), time (preoperative
      visit vs day of surgery), and target (lesion vs clip). RESULTS: Twenty-five
      patients with 26 lesions were enrolled, and 19 patients returned for all imaging
      procedures. The mean lesion size was 12 mm (range, 5-24 mm). Adequate marker clip
      visibility assessed by the surgeons decreased from 80% (20 of 25) at the
      preoperative appointment to 65% (11 of 17) in the operating room, but the
      difference was not significant (P=.27). Visibilities of the lesions and clips
      were similar at the preoperative appointment (P=.61), but the clips were
      significantly less visible on the day of operation (P=.03). CONCLUSION: The
      sonographic visibility of collagen-based marker clips is variable and likely
      decreases over time but may be adequate to guide intraoperative surgical excision
      in many cases.

PMID- 20042351
TI  - Diagnostic performance of a prototype dual-energy chest imaging system ROC
      analysis.
AB  - RATIONALE AND OBJECTIVES: To assess the performance of an experimental prototype
      dual-energy (DE) chest imaging system in comparison to digital radiography (DR)
      in detection and characterization of lung lesions using receiver-operating
      characteristic (ROC) tests. MATERIALS AND METHODS: A cohort of 129 patients (80
      M, 49 F; mean age, 64.8 years) was drawn from a trial of patients referred for
      percutaneous biopsy of a lung lesion. DR and DE images were acquired of each
      patient (posteroanterior view) before biopsy using a prototype system developed
      in our laboratory. The system incorporated a flat-panel detector and previously
      reported imaging techniques optimized such that the total dose for the DE image
      was equivalent to that of a DR acquisition. Each DE image was decomposed to three
      components (soft-tissue, bone, and composite "equivalent radiograph") by log
      subtraction with optimized noise reduction techniques. ROC tests were performed
      to evaluate the diagnostic performance of DR imaging in comparison to DE for
      nodule detection, with 258 left/right "half-chest" images derived from the 129
      cases to give a roughly equal number of disease and normal cases. Five chest
      radiologists scored 258 half-chest DE and 258 half-chest DR (516 in total) images
      on a 5-point scale, and results (including ROC and area under the curve [AUC])
      were analyzed using the ROCkit toolkit. Statistical significance in the observed
      differences was evaluated in terms of P values determined by a z test.
      Performance was analyzed for all cases pooled (258 DE vs. 258 DR images) and by
      retrospective stratification of the data according to nodule size, density,
      gender, lung region, and chest thickness. RESULTS: For results pooled over the
      entire cohort, there was no significant difference in ROC performance between DE
      and DR (AUC(DE) = 0.795 AUC(DR) = 0.789; P = .696). This finding is believed to
      be due to a large portion of lesions that were fairly conspicuous in either
      modality. In retrospective analysis of subgroups, a significant advantage was
      measured for DE imaging of small nodules (<1 cm diameter; AUC(DE) = 0.778;
      AUC(DR) = 0.706; P = .056), for nodules located in the right upper lobe (AUC(DE)
      = 0.836; AUC(DR) = 0.779; P = .003), and nodules located in right lower lobe
      (AUC(DE) = 0.804; AUC(DR) = 0.752; P = .054). DE imaging provided a clinically
      significant differential diagnosis in approximately one third of patients
      (49/158) (ie, disease cases in which the lesion was correctly identified in DE
      [(ROC rating > or =3], but missed in DR [ROC rating < or =2]). DE imaging also
      appeared to provide more definitive diagnosis (ie, a greater proportion of ROC
      ratings = 5 and 1 for identification of disease and normal cases, respectively),
      which presumably translates to increased confidence and a steeper ROC curve (even
      if the AUC are the same). CONCLUSIONS: DE imaging at dose equivalent to DR
      exhibited similar overall ROC performance to DR, although the radiologists noted
      qualitatively improved visualization (eg, improved characterization of lesion
      margins, visibility of calcifications and rib fractures). DE imaging demonstrated
      significant improvement in diagnostic performance for specific subgroups,
      including subcentimeter lung lesions and lesions in the right upper lobe, each of
      which is a potentially important factor in detecting early-stage malignancy.

PMID- 20042352
TI  - T2-weighted MRI of the upper abdomen: comparison of four fat-suppressed T2
      weighted sequences including PROPELLER (BLADE) technique.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to compare four different fat
      suppressed T2-weighted sequences with different techniques with regard to image
      quality and lesion detection in upper abdominal magnetic resonance imaging (MRI)
      scans. MATERIALS AND METHODS: Thirty-two consecutive patients referred for upper
      abdominal MRI for the evaluation of various suspected pathologies were included
      in this study. Different T2-weighted sequences (free-breathing navigator
      triggered turbo spin-echo [TSE], free-breathing navigator-triggered TSE with
      restore pulse (RP), breath-hold TSE with RP, and free-breathing navigator
      triggered TSE with RP using the periodically rotated overlapping parallel lines
      with enhanced reconstruction technique [using BLADE, a Siemens implementation of
      this technique]) were used on all patients. All images were assessed
      independently by two radiologists. Assessments of motion artifacts; the edge
      sharpness of the liver, pancreas, and intrahepatic vessels; depictions of the
      intrahepatic vessels; and overall image quality were performed qualitatively.
      Quantitative analysis was performed by calculation of the signal-to-noise ratios
      for liver tissue and gallbladder as well as contrast-to-noise ratios of liver to
      spleen. RESULTS: Liver and gallbladder signal-to-noise ratios as well as liver to
      spleen contrast-to-noise ratios were significantly higher (P < .05) for the BLADE
      technique compared to all other sequences. In qualitative analysis, the severity
      of motion artifacts was significantly lower with T2-weighted free-breathing
      navigator-triggered BLADE sequences compared to other sequences (P < .01). The
      edge sharpness of the liver, pancreas, and intrahepatic vessels; depictions of
      the intrahepatic vessels; and overall image quality were significantly better
      with the BLADE sequence (P < .05). CONCLUSION: The T2-weighted free-breathing
      navigator-triggered TSE sequence with the BLADE technique is a promising approach
      for reducing motion artifacts and improving image quality in upper abdominal MRI
      scans.

PMID- 20042353
TI  - Pestivirus infection in sheep and goats in West Austria.
AB  - Blood samples from 3112 sheep (185 flocks) and 1196 goats (163 flocks) from the
      Western region of Austria were tested for pestivirus-specific RNA. In this area,
      communal Alpine pasturing of sheep, cattle and goats is an important part of
      farming. The prevalence of sheep persistently-infected (PI) with pestivirus was
      0.32% (10 animals) and the PI animals originated from five flocks (2.7% of those
      investigated). In goats, only one PI animal (0.08%) was detected. Sequence
      analysis of the 5'-end untranslated region (UTR) revealed that the strains of
      Border disease virus (BDV) detected were closely related to genotype 3 but the PI
      animals did not show any clinical signs of Border disease. The goat was PI with
      bovine viral diarrhoea virus-1 (BVDV-1). On one farm a high abortion rate among
      sheep had been observed 1year before the study was carried out but the other
      farms did not show any evidence of reproductive failures. Pestiviruses are
      endemic in small ruminants in some Alpine regions of Austria and PI healthy
      animals as described here have a key epidemiological role. A successful BVDV
      eradication programme in Austria will create highly pestivirus-susceptible cattle
      populations. Sheep and goats present a high risk for the reintroduction of
      pestiviruses to cattle herds because they are less likely to be considered to be
      PI. The results underline the need for the immediate consideration of small
      ruminants in eradication programmes.

PMID- 20042354
TI  - The utility of estimated breeding values for inherited disorders of dogs.

PMID- 20042355
TI  - Echo-time independent signal modulations for strongly coupled systems in triple
      echo localization schemes: an extension of S-PRESS editing.
AB  - The double spin-echo point resolved spectroscopy sequence (PRESS) is a widely
      used method and standard in clinical MR spectroscopy. Existence of important J
      modulations at constant echo times, depending on the temporal delays between the
      rf-pulses, have been demonstrated recently for strongly coupled spin systems and
      were exploited for difference editing, removing singlets from the spectrum
      (strong-coupling PRESS, S-PRESS). A drawback of this method for in vivo
      applications is that large signal modulations needed for difference editing occur
      only at relatively long echo times. In this work we demonstrate that, by simply
      adding a third refocusing pulse (3S-PRESS), difference editing becomes possible
      at substantially shorter echo times while, as applied to citrate, more favorable
      lineshapes can be obtained. For the example of an AB system an analytical
      description of the MR signal, obtained with this triple refocusing sequence (3S
      PRESS), is provided.

PMID- 20042356
TI  - Clinical trials: curing a critical deficiency in metabolic medicine.
AB  - The treatment of rare disorders is often driven by experience and expert opinion
      rather than formal clinical trials because of the significant barriers in place
      to conducting traditional random, placebo controlled, national studies. Dr. Doug
      Kerr graphically illustrates these problems in the treatment of inborn errors of
      mitochondrial oxidative phosphorylation as reviewed elsewhere in this issue. New
      models and additional funding for studying the ultra rare diseases that are the
      purview of metabolic medicine are desperately needed to move the field forward in
      an evidence-based fashion. In this commentary, the challenges associated with
      conducting clinical trials in ultra-rare disorders are discussed and potential
      solutions suggested.

PMID- 20042357
TI  - [Extracorporeal photochemotherapy].
AB  - Photopheresis or extracorporeal photochemotherapy (ECP) is a cellular therapy
      which combines a leukapheresis followed by ex vivo treatment using psoralen and
      ultraviolet A irradiation before reinfusion into the patient. Its mechanisms of
      action remain unclear and selective photodestruction of leukocytes cannot explain
      the long-lasting immunomodulatory effects. Recent studies demonstrated that ECP
      down regulates the immune response and induces tolerance through the maturation
      of dendritic cells and the production of regulatory T cells. Based on these
      effects, ECP is mainly used for treatment of Sezary syndrome, graft-versus-host
      disease, organ graft rejection and autoimmune diseases. However, it is still not
      clear how ECP both activates tumor immunity against cutaneous T-cell lymphoma and
      induces tolerance in autoreactive disorders. In addition, the use of adjuvant
      therapies, the long-term effects and various treatment protocols remain to be
      investigated along with the specific indications.

PMID- 20042358
TI  - Sonochemical stabilization of ultrafine colloidal biocompatible magnetite
      nanoparticles using amino acid, L-arginine, for possible bio applications.
AB  - Materials obtained by the synergistic combination of nanotechnology and
      biomedicine are an important source of drug delivery and other health care
      related applications. The anchoring of amino acids onto the surface of nano-sized
      magnetite is one such example. Herein, we report on the binding of a semi
      essential amino acid, L-arginine, onto the surface of nano magnetite, creating a
      stable aqueous suspension by an in situ one-step method using sonochemical
      synthesis. An ex situ two-step process was also attempted, but was soon discarded
      owing to the relative short duration of the suspension attributed to increase in
      particle size and lower extent of binding. The initial concentration of the amino
      acid was found to play an important role in controlling the particle size and
      also the binding motif. Lower concentrations of arginine were found to favor the
      formation of elongated tubular structures, while at higher concentrations, the
      elongated structures were less prominent and arginine was found to be adsorbed
      onto the surface of the magnetite. This surface-functionalized nanomagnetite with
      amino acids could become a promising vehicle for drug delivery.

PMID- 20042359
TI  - Extrapolating glioma invasion margin in brain magnetic resonance images:
      suggesting new irradiation margins.
AB  - Radiotherapy for brain glioma treatment relies on magnetic resonance (MR) and
      computed tomography (CT) images. These images provide information on the spatial
      extent of the tumor, but can only visualize parts of the tumor where cancerous
      cells are dense enough, masking the low density infiltration. In radiotherapy, a
      2 m constant margin around the tumor is taken to account for this uncertainty.
      This approach however, does not consider the growth dynamics of gliomas,
      particularly the differential motility of tumor cells in the white and in the
      gray matter. In this article, we propose a novel method for estimating the full
      extent of the tumor infiltration starting from its visible mass in the patients'
      MR images. This estimation problem is a time independent problem where we do not
      have information about the temporal evolution of the pathology nor its initial
      conditions. Based on the reaction-diffusion models widely used in the literature,
      we derive a method to solve this extrapolation problem. Later, we use this
      formulation to tailor new tumor specific variable irradiation margins. We perform
      geometrical comparisons between the conventional constant and the proposed
      variable margins through determining the amount of targeted tumor cells and
      healthy tissue in the case of synthetic tumors. Results of these experiments
      suggest that the variable margin could be more effective at targeting cancerous
      cells and preserving healthy tissue.

PMID- 20042360
TI  - Current silicone hydrogel UVR blocking lenses and their associated protection
      factors.
AB  - PURPOSE: Ultraviolet radiation (UVR) blocking contact lenses provides ocular
      protection factors (PF) that vary with lens thickness and the nature of the
      polymer dopant. This study measured the UVR PF of silicone hydrogel lenses
      outdoors and compares this to known methods for determining PF mathematically.
      METHODS: Ambient measurements were taken using an UVA-B radiometer, adapted to
      hold the test lenses over its sensor to quantify their UVR blocking capabilities.
      The UVR blocking silicone hydrogel lenses tested included galyfilcon A,
      senofilcon A, and enfilcon A. The first UVR blocking hydrogel lens, vasurfilcon
      A, and a non-blocking silicone hydrogel lens, lotrafilcon B, served as a
      comparison. Lens transmittance at the centre and periphery was measured and PF
      calculated to predict signal reduction for comparison with field measurements.
      RESULTS: There was a significant range of cut-off wavelengths across the lenses,
      ranging from 370nm for enfilcon A to 390nm for vasurfilcon A, with lotrafilcon B
      transmitting down to 265nm, with a 3nm shift from centre to periphery across the 
      3.00 D UVR blockers. The UVR reduction calculated from the transmittance data
      correlates well with field data, ranging from 90-98% for the UVR blockers to 13%
      for the non-blocker. CONCLUSIONS: The silicone hydrogel lenses showed a wide
      range of transmittance curves with increasing PF from centre to periphery. PF
      calculations work well but do not always compare precisely with measured data due
      to factors such as sensor spectral response and the nature of the incident solar
      spectrum.

PMID- 20042361
TI  - Simultaneous chemiluminescence determination of thebaine and noscapine using
      support vector machine regression.
AB  - In this work, a batch chemiluminescence (CL) method has been proposed for the
      simultaneous determination of two structurally similar alkaloids, noscapine and
      thebaine. The method is based on the kinetic distinction of the CL reactions of
      noscapine and thebaine with Ru(bipy)(3)(2+) and Ce(IV) system in a sulfuric acid
      medium. The least squared support vector machine (LS-SVM) regression was applied
      for relating the concentrations of both compounds to their CL profiles. The
      parameters of the model consisting of sigma(2) and gamma were optimized by
      constructing LS-SVM models with all possible combinations of these two parameters
      to select the model with the minimum root mean squared error of cross validation
      (RMSECV) as the best. The parameters of this model were then selected as
      optimized values. Under the optimized experimental conditions for both compounds,
      the detection limits obtained using the LS-SVM regression were 0.08 and 0.1
      micromo lL(-1) for noscapine and thebaine, respectively. The proposed method was
      utilized for the simultaneous determination of the compounds in pharmaceutical
      formulations and plasma samples with satisfactory results.

PMID- 20042362
TI  - Structural parameters and vibrational spectra of a series of zinc meso
      phenylporphyrins: a DFT and experimental study.
AB  - The influences of meso-phenyl substitution on the geometric structure and
      vibrational spectra have been studied by DFT calculation (B3LYP/6-31G(d)) and
      experiment on a series of zinc porphyrins (ZnTPP: zinc 5,10,15,20
      tetraphenylporphyrin; ZnTrPP: zinc 5,10,15-triphenylporphryin; ZnDPP: zinc 5,15
      dipenylporphyirn; ZnMPP: zinc 5-monophenylporphyrin; ZnP: zinc porphine).
      Calculation indicates that meso-phenyl substitution gives rise to slight out-of
      plane distortion but significant in-plane distortion, especially for the
      configuration around C(m) atom, to zinc porphyrin. The assignment of experimental
      vibrational spectra was proposed mainly on the basis of calculation. Different
      shifting tendency upon meso-phenyl substitution is observed for different
      structure-sensitive bands, such as the shifting of nu(2), nu(3), nu(6), and nu(8)
      modes toward higher frequencies and nu(4) and nu(28) modes toward lower
      frequencies, upon meso-phenyl substitution. This is attributed primarily to in
      plane nuclear reorganization effect (IPNR), though the contribution from out-of
      plane distortion cannot be excluded completely. Analysis on vibrational structure
      reveals that asymmetric meso-phenyl substitution, especially the 5,15-diphenyl
      substitution of ZnDPP, brings about asymmetric vibrational displacement, or even
      splitting of vibrational structure to normal modes involving mainly the motion of
      meso-C(m). This is ascribed to the reduction of symmetry of porphyrin skeleton
      caused by asymmetric meso-phenyl substitution.

PMID- 20042363
TI  - A simple and efficient anionic chromogenic chemosensor based on 2,4
      dinitrodiphenylamine in dimethyl sulfoxide and in dimethyl sulfoxide-water
      mixtures.
AB  - Solutions of 2,4-dinitrodiphenylamine (1) in dimethylsulfoxide (DMSO) are
      colorless but upon deprotonation they become red. Addition of various anionic
      species (HSO(4)(-), H(2)PO(4)(-), NO(3)(-), CN(-), CH(3)COO(-), F(-), Cl(-), Br(
      ), and I(-)) to solutions of 1 revealed that only CN(-), F(-), CH(3)COO(-), and
      H(2)PO(4)(-) led to the appearance of the red color in solution. The presence of
      increasing amounts of water in solutions containing 1 made it progressively
      selective toward CN(-) and the system with the addition of 4.3% (v/v) of water
      was highly selective for CN(-) among all anions studied. The experimental data
      collected indicated that proton transfer from 1 to the anion occurs, and a model
      was used to explain the experimental results, which considers two 1:anion
      stoichiometries, 1:1 and 1:2. For the latter, the data suggest that the anion
      forms firstly a hydrogen-bonded complex with a second anion equivalent necessary
      for the abstraction of the proton, with the formation of a [HA(2)](-) complex.
      The study performed here demonstrates the important role of the environment of
      the anion and 1 for the efficiency of the chromogenic chemosensor. Besides the
      different affinities of each anion for water, the solvation of both the anion and
      1 is responsible for reducing the interaction between these species. In small
      amounts, water or hydrogen-bonded DMSO-water complexes are able to stabilize the
      conjugated base of 1 through hydrogen bonding, making 1 more acidic, which
      explains the change from 1:1 and 1:2 toward 1:1 1:anion stoichiometry upon
      addition of water. In addition, water is able to solvate the anion and also 1,
      which hinders the formation of 1:1 hydrogen-bonded 1:anion complexes prior to the
      abstraction of the proton.

PMID- 20042364
TI  - Determination of lead(II) in fly ash leachate using a newly developed simple
      spectrophotometric method.
AB  - A new simple method for the spectrophotometric determination of Pb(II) in fly ash
      leachates was developed. These leachates tend to contain a large amount of Ca(II)
      and Zn(II); this interferes with spectrophotometric determination of Pb(II) when
      conventional colorimetric agents are used. A copolymer consisting of
      protoporphyrin IX disodium salt and acrylamide was synthesized as a colorimetric
      agent. A measuring reagent containing ethylenediamine-N,N'-dipropionic acid
      (EDDP) as a masking agent for Zn(II) and an appropriate amount of Ca(II) together
      with the copolymer was applied to determine Pb(II). The temporal change in the
      absorption spectrum of the measuring reagent was acquired with a newly developed
      portable spectrophotometer for this method. The composition of EDDP and Ca(II) in
      the measuring reagent was optimized to measure leachates contaminated with Ca(II)
      and Zn(II). The detection limit and relative standard deviation of Pb(II)
      measured using the optimized method were 0.05 mg L(-1) and 2.3%, respectively.
      The tolerance limits for Ca(II) and Zn(II) contaminants, where errors of less
      than 10% were allowed at a concentration of 0.5 mg L(-1) Pb(II), were 4000 and 4
      mg L(-1), respectively. The determination of Pb(II) in various samples of actual
      leachates from incinerator fly ash was examined with this method. The obtained
      values correlated well with those obtained by flame atomic absorption
      spectroscopy.

PMID- 20042365
TI  - IR and NMR spectra, intramolecular hydrogen bonding and conformations of para
      tert-butyl-aminothiacalix[4]arene in solid state and chloroform solution.
AB  - It is demonstrated that dissolution of aminothiacalix[4]arene in chloroform
      results in transformation of 1,3-alternate conformation, adopted in single
      crystal and bulk polycrystalline solids, to the pinched-cone form. This conformer
      is stabilised by the intramolecular hydrogen bonds of two distal amino-groups
      acting as H-donors with another two amino moieties that appear as H-acceptors.
      The H-bonds cause quite small (ca. 10-20 cm(-1)) red shift of the IR bands of the
      NH(2) stretching vibrations, which suggests rather weak NHcdots, three dots,
      centeredN hydrogen bonding. This latter is sufficient to stabilize the pinched
      cone conformation in the chloroform solution, but the energy gap between the
      pinched-cone and other conformations is small, and solid-state intermolecular
      forces easily overcome it, leading to realisation of the 1,3-alternate conformer.
      The comparison of the DFT computed and experimental vibrational and NMR spectra
      demonstrates good quality of present quantum-chemical computations, allows
      complete interpretation of the spectra and reveals simple IR and NMR
      spectroscopic markers of the conformers of aminothiacalix[4]arenes.

PMID- 20042366
TI  - Raman spectroscopic study of the antimony bearing mineral langbanite.
AB  - Raman spectroscopy has been used to characterise the antimonate mineral
      langbanite (Mn, Ca, Fe)(4)(2+)(Mn(3+), Fe(3+))(9)Sb(5+)Si(2)O(24). The mineral is
      characterised by a series of peaks in the 850-1200 cm(-1) region. Raman bands
      observed at 872 and 897cm(-1) are assigned to SbO antisymmetric and symmetric
      stretching vibrations, respectively. Associated with the SbO units are the bands
      at 330, 351 and 386 cm(-1) attributed to OSbO bending modes. Four Raman bands
      observed at 964, 986, 1012 and 1034 cm(-1) are assigned to SiO stretching
      vibrations. The observation of multiple SiO Raman bands provides evidence for the
      non-equivalence of the SiO units in the langbanite structure. Associated with the
      SiO units are the Raman bands at 542, 558, 646 and 671 cm(-1) attributed to OSiO
      bending modes. Low intensity bands are observed at 1130, 1200, 1432, 1718 and
      1947 cm(-1) and are probably associated with delta SbOH deformation modes. Raman
      bands are observed at 3076 and 3476 cm(-1) and are assigned to strongly bonded
      water molecules involved in the langbanite structure. A sharp Raman band at 3680
      cm(-1) are assigned to OH stretching vibrations. Raman spectroscopy provides
      evidence for water and OH units in the structure of langbanite and brings the
      formula of the mineral into question.

PMID- 20042367
TI  - Lymphotropic polyomavirus is detected in peripheral blood from immunocompromised
      and healthy subjects.
AB  - BACKGROUND: Lymphotropic Polyomavirus (LPV) was isolated from a B-lymphoblastoid
      cell line of an African green monkey. This virus shares some characteristics with
      human polyomaviruses, but it is antigenically distinct from BK Virus (BKV) and JC
      Virus (JCV). Seroepidemiological studies revealed that human sera react in the
      presence of LPV antigens, and, recently, the viral genome was amplified in the
      peripheral blood from patients affected with HIV-related leukoencephalopathies.
      OBJECTIVES: The aims of the study were to investigate and compare the presence of
      LPV DNA with that of JCV and BKV in different biological samples and patient
      groups. STUDY DESIGN: LPV, JCV and BKV DNA were searched and quantified in
      peripheral blood and CSF from HIV+ patients and in peripheral blood from healthy
      subjects. RESULTS: The LPV genome was detected in peripheral blood of both HIV+
      patients and healthy subjects, with a prevalence of 7.2% and 4.7% respectively,
      but not in CSF. However, its presence was less frequent than that of JCV and BKV.
      CONCLUSIONS: The amplification of LPV genome from human peripheral blood confirms
      the fact that LPV can infect the human population. LPV DNA was amplified from
      patients affected with HIV-related leukoencephalopathies but also from HIV
      patients without neurological disorders and from healthy subjects. Therefore, the
      results do not support the hypothesis of an association between LPV infection and
      any neurological disease. However, given their high similarity, it is possible
      that LPV, as well as BKV and JCV, could establish latency in humans and cause
      disease only in rare circumstances.

PMID- 20042368
TI  - Antibiotic therapy may improve idiopathic restless legs syndrome: prospective,
      open-label pilot study of rifaximin, a nonsystemic antibiotic.

PMID- 20042369
TI  - A Poisson-based adaptive affinity propagation clustering for SAGE data.
AB  - Serial analysis of gene expression (SAGE) is a powerful tool to obtain gene
      expression profiles. Clustering analysis is a valuable technique for analyzing
      SAGE data. In this paper, we propose an adaptive clustering method for SAGE data
      analysis, namely, PoissonAPS. The method incorporates a novel clustering
      algorithm, Affinity Propagation (AP). While AP algorithm has demonstrated good
      performance on many different data sets, it also faces several limitations.
      PoissonAPS overcomes the limitations of AP using the clustering validation
      measure as a cost function of merging and splitting, and as a result, it can
      automatically cluster SAGE data without user-specified parameters. We evaluated
      PoissonAPS and compared its performance with other methods on several real life
      SAGE datasets. The experimental results show that PoissonAPS can produce
      meaningful and interpretable clusters for SAGE data.

PMID- 20042370
TI  - EEG abnormalities and epilepsy in autistic spectrum disorders: clinical and
      familial correlates.
AB  - Our aim was to examine the characteristics of EEG findings and epilepsy in
      autistic spectrum disorders (ASD) and the associated clinical and familial risk
      factors. Fifty-seven children (86% male) with ASD, mean age 82+/-36.2 months,
      were included in the study. Thirty-nine (68.4%) children had the diagnosis of
      autism, 15 (26.3%) had Pervasive Developmental Disorder Not Otherwise Specified,
      and 3 (5.3%) had high-functioning autism. One hour of sleep and/or awake EEG
      recordings was obtained for each child. All patients were evaluated with respect
      to clinical and familial characteristics and with the Childhood Autism Rating
      Scale, the Autism Behavior Checklist, and the Aberrant Behavior Checklist. The
      frequency of interictal epileptiform EEG abnormalities (IIEAs) was 24.6% (n=14),
      and the frequency of epilepsy was 14.2% (n=8). IIEAs were associated with a
      diagnosis of epilepsy (P=0.0001), Childhood Autism Rating Scale Activity scores
      (P=0.047), and a history of asthma and allergy (P=0.044). Epilepsy was associated
      with a family history of epilepsy (P=0.049) and psychiatric problems in the
      mother during pregnancy (P=0.0026). Future studies with larger samples will help
      to clarify the possible associations of epilepsy/IIEAs with asthma/allergy,
      hyperactivity, and familial factors in ASD.

PMID- 20042371
TI  - Did Vincent van Gogh eat fish?

PMID- 20042372
TI  - Familiarity with, knowledge of, and attitudes toward epilepsy among teachers in
      Korean elementary schools.
AB  - We investigated familiarity with, knowledge of, and attitudes toward epilepsy
      among teachers in elementary schools in Korea, where there is profound prejudice
      against epilepsy. Most of the teachers thought that epilepsy is a genetic
      disease. They agreed that children with epilepsy (CWE) should attend regular
      classes (although with some restriction of school activities) because their
      academic achievement would be comparable to that of children without epilepsy.
      However, half of the teachers opposed having CWE in their own classes because
      they feared a child having a seizure during class and they felt they lacked
      knowledge of first-aid for seizures. Those teachers who had inaccurate clinical
      knowledge of epilepsy also demonstrated negative attitudes toward the marriage
      and employment of persons with epilepsy. We conclude that information about
      epilepsy should be included in teacher training programs so as to increase their
      level of knowledge of epilepsy and correct prejudices against epilepsy.

PMID- 20042374
TI  - An alternative hypothesis for right precordial ST-segment elevation in structural
      heart disease with diminished sodium current.

PMID- 20042373
TI  - Cellular basis for atrial fibrillation in an experimental model of short QT1:
      implications for a pharmacological approach to therapy.
AB  - BACKGROUND: Short QT (SQT) syndrome (SQT) 1 is an inherited sudden death syndrome
      often associated with atrial fibrillation (AF). We examined the cellular basis
      for AF in a newly developed experimental atrial model of SQT1. METHODS: Action
      potentials (APs) were recorded from the pectinate muscle (PM) and crista
      terminalis (CT) regions of coronary-perfused canine right atrial preparations,
      together with a pseudoelectrocardiogram. The I(Kr) agonist PD-118057 (20 microM)
      was used to mimic the gain of function in I(Kr) known to underlie SQT1. RESULTS:
      The I(Kr) agonist significantly abbreviated the AP duration (APD) of CT and PM
      and of the effective refractory period (ERP) measured in PM (n = 28). Spatial
      dispersion of repolarization (SDR), defined as inter-regional differences of APD,
      increased from 27 +/- 17 ms to 51 +/- 32 ms (P = .002; n = 28). AF could be
      induced by a single premature stimulus after but not before exposure to PD-118057
      in 26/28 (93%) preparations. Quinidine (10 microM), which prolonged APD and ERP,
      but not lidocaine (20 microM) or E-4031 (5 microM), which prolonged only ERP or
      APD, respectively, was effective in preventing the PD-118057-mediated AF. In the
      presence of PD-118057, isoproterenol (100 nM) further abbreviated both APD and
      ERP and facilitated induction of sustained AF in five of six preparations.
      CONCLUSIONS: The I(Kr) agonist recapitulates the electrophysiologic and
      arrhythmic manifestations of SQT1. Abbreviation of APD and ERP and amplification
      of SDR predispose to the development of AF by creating the substrate for reentry.
      Quinidine, but not E-4031 or lidocaine, was effective in preventing AF in this
      setting.

PMID- 20042375
TI  - KCNE2 modulation of Kv4.3 current and its potential role in fatal rhythm
      disorders.
AB  - BACKGROUND: The transient outward current I(to) is of critical importance in
      regulating myocardial electrical properties during the very early phase of the
      action potential. The auxiliary beta subunit KCNE2 recently was shown to modulate
      I(to). OBJECTIVE: The purpose of this study was to examine the contributions of
      KCNE2 and its two published variants (M54T, I57T) to I(to). METHODS: The
      functional interaction between Kv4.3 (alpha subunit of human I(to)) and wild-type
      (WT), M54T, and I57T KCNE2, expressed in a heterologous cell line, was studied
      using patch-clamp techniques. RESULTS: Compared to expression of Kv4.3 alone, co
      expression of WT KCNE2 significantly reduced peak current density, slowed the
      rate of inactivation, and caused a positive shift of voltage dependence of steady
      state inactivation curve. These modifications rendered Kv4.3 channels more
      similar to native cardiac I(to). Both M54T and I57T variants significantly
      increased I(to) current density and slowed the inactivation rate compared with WT
      KCNE2. Moreover, both variants accelerated the recovery from inactivation.
      CONCLUSION: The study results suggest that KCNE2 plays a critical role in the
      normal function of the native I(to) channel complex in human heart and that M54T
      and I57T variants lead to a gain of function of I(to), which may contribute to
      generating potential arrhythmogeneity and pathogenesis for inherited fatal rhythm
      disorders.

PMID- 20042376
TI  - Effects of diabetes on expression of glial fibrillary acidic protein and
      neurotrophins in rat colon.
AB  - Diabetes can result in loss of enteric neurons and subsequent gastrointestinal
      complications, but the influence of diabetes on the expression of glial
      fibrillary acidic protein (GFAP) and neurotrophins in gut remains unknown. The
      aim of this study was to determine the changes of GFAP and neurotrophins in the
      colon of diabetic rats. The distribution of the glial marker-GFAP was explored by
      immunofluorescence histochemistry and western blot in colons of streptozotocin
      (STZ)-diabetic and age-matched control rats. And the expression of glia cell
      derived neurotrophic factor (GDNF), neurotrophin 3 (NT-3) and nerve growth factor
      (NGF) was analyzed by real-time PCR and western blot. Studies were carried out at
      4 and 12weeks of diabetes duration. Immunostaining and western blot showed
      diabetes induced a decrease in the intensity of staining of GFAP positive enteric
      glial cells (EGCs) and GFAP protein levels at 4weeks and attenuated GFAP
      expression was more evident at 12weeks. Moreover, mRNA and protein analysis
      indicated that the levels of GDNF, NT-3 and NGF were down-regulated in diabetic
      rats. These findings suggest that the induction of diabetes is associated with a
      reduction in GFAP and neurotrophins expression in the colon, which may affect the
      role of EGCs and neurotrophins in the enteric plexus. This in turn may partly
      contribute to the physiopathologic changes associated with diabetic state in the
      gastrointestinal tract.

PMID- 20042377
TI  - Use of a molecular beacon to track the activity of base excision repair protein
      OGG1 in live cells.
AB  - An abundant form of DNA damage caused by reactive oxygen species is 8-oxo-7,8
      dihydroguanine for which the base excision repair protein 8-oxoguanine-DNA
      glycosylase 1 (OGG1) is a major repair enzyme. To assess the location and
      intracellular activity of the OGG1 protein in response to oxidative stress, we
      have utilised a fluorescence-quench molecular beacon switch containing a 8-oxo
      dG:C base pair and a fluorescent and quencher molecule at opposite ends of a
      hairpin oligonucleotide. Oxidative stress was induced by treatment with potassium
      bromate. Flow cytometry demonstrated a concentration-dependent increase in the
      activity of OGG1 that was detected by the fluorescence produced when the
      oligonucleotide was cleaved in the cells treated with potassium bromate. This
      signal is highly specific and not detectable in OGG1 knock out cells. Induction
      of OGG1 activity is not a result of induction of OGG1 gene expression as assessed
      by qPCR suggesting a role for protein stabilisation or increased OGG1 catalytic
      activity. High resolution confocal microscopy pinpointed the location of the
      fluorescent molecular beacon in live cells to perinuclear regions that were
      identified as mitochondria by co-staining with mitotracker dye. There is no
      evidence of cut beacon within the nuclear compartment of the cell. Control
      experiments with a positive control beacon (G:C base pair and lacking the DAB
      quencher) did not result in mitochondrial localisation of fluorescence signal
      indicating that the dye does not accumulate in mitochondria independent of OGG1
      activity. Furthermore, faint nuclear staining was apparent confirming that the
      beacon structure is able to enter the nucleus. In conclusion, these data indicate
      that the mitochondria are the major site for OGG1 repair activity under
      conditions of oxidative stress.

PMID- 20042378
TI  - Validation of an electrospray ionization LC/MS/MS method for quantitative
      analysis of vincristine in human plasma samples.
AB  - Vincristine is a natural vinca alkaloid widely used in paediatric cancer
      treatment. Vincristine pharmacokinetics has been already studied, but few data
      are available in paediatric populations. A sensitive and specific liquid
      chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for the
      quantification of vincristine in plasma in order to investigate pharmacokinetics
      in a paediatric population. Two hundred microliters of plasma was added to
      vinblastine, used as internal standard. Chromatographic separation was achieved
      on a C8 HPLC column (Phenomenex Luna 50 mm x 2.0 mm, 3.0 microm) with a mobile
      phase gradient at a flow rate of 0.2 ml/min. Quantification was performed using
      the transition of 825.4-->765.4 (m/z) for vincristine and 811.4-->751.4 (m/z) for
      vinblastine. Chromatographic separation was achieved in 8 min. The limit of
      quantification was 0.25 ng/ml with a precision of 10.2% and an accuracy of 99.6%.
      The calibration curve was linear up to 50.0 ng/ml. Intra-day precision and
      accuracy ranged from 6.3% to 10% and from 91.9% to 100.8%, respectively. Inter
      assay precision and accuracy ranged from 3.8% to 9.7% and from 93.5% to 100.5%,
      respectively. No significant matrix effect was observed for vincristine. A rapid,
      specific and sensitive LC/MS/MS method for quantification of vincristine in human
      plasma was developed and is now successfully applied for pharmacokinetic studies
      in paediatric patients.

PMID- 20042379
TI  - Identification of cardiac glycosides in fractions from Periploca forrestii by
      high-performance liquid chromatography/diode-array detection/electrospray
      ionization multi-stage tandem mass spectrometry and liquid chromatography/nuclear
      magnetic resonance.
AB  - Cardiac glycosides are a class of naturally occurring compounds that are
      characterized by some interesting biological activities and are widely
      distributed in the plant kingdom and can also be found in some animals. There is
      an interest in the chemical characterization of these molecules due to their
      toxicity and their use in medicines. In the study reported here, a combination of
      electrospray ionization tandem mass spectrometry with high-performance liquid
      chromatography equipped with diode-array detector (HPLC-DAD/ESI-MS(n)), and
      hyphenation to both liquid chromatography and nuclear magnetic resonance
      spectroscopy (HPLC/NMR) were utilized for the on-line analyses of cardiac
      glycosides from Periploca forrestii. The fragmentation patterns and (1)H NMR
      spectra of nine isolated cardiac glycosides were investigated; their
      fragmentation rules and (1)H NMR spectral characteristics were summarized and
      applied to the structural identification of similar constituents in fractions
      from P. forrestii. As a result, a total of nine trace cardiac glycosides were
      tentatively determined by analyses of accurate molecular masses, representative
      fragment ions and characteristic (1)H NMR signals provided by HPLC/high
      resolution mass spectrometry (HRMS), HPLC-DAD/ESI-MS(n) and HPLC/(1)H NMR
      experiments, respectively. Of these, eight (2-9) are new compounds and one (1) is
      reported from P. forrestii for the first time. Results of the present study can
      benefit the rapid identification and targeted isolation of new cardiac glycosides
      from crude plant extracts.

PMID- 20042380
TI  - Simultaneous determination of quinolones for veterinary use by high-performance
      liquid chromatography with electrochemical detection.
AB  - A selective method based on high-performance liquid chromatography with
      electrochemical detection (HPLC-ECD) has been developed to enable simultaneous
      determination of three fluoroquinolones (FQs), namely danofloxacin (DANO),
      difloxacin (DIFLO) and sarafloxacin (SARA). The fluoroquinolones are separated on
      a Novapack C-18 column and detected in a high sensitivity amperometric cell at a
      potential of +0.8 V. Solid-phase extraction was used for the extraction of the
      analytes in real samples. The range of concentration examined varied from 10 to
      150 ng g(-1) for danofloxacin, from 25 to 100 ng g(-1) for sarafloxacin and from
      50 to 315 ng g(-1) for difloxacin, respectively. The method presents detection
      limits under 10 ng g(-1) and recoveries around 90% for the three analytes have
      been obtained in the experiments with fortified samples. This HPLC-ECD approach
      can be useful in the routine analysis of antibacterial residues being less
      expensive and less complicated than other more powerful tools as hyphenated
      techniques.

PMID- 20042382
TI  - [Nutrition and bone health in children].
AB  - Adequate nutrient intake is an important component of maintaining bone health,
      and should be encouraged in all age groups. Osteoporosis is a disease in which
      the density and quality of bone are reduced, leading to weakness of the skeleton
      and increased risk of fracture, particularly of the spine and hip. Osteoporosis
      is a global public health problem which currently affects a great proportion of
      women and men, and is increasing in significance as the population of the world
      both grows in size and lives longer. Bone loss does not have any symptoms, and
      often the first sign of having osteoporosis is a fracture. Studies in children
      and adolescents have shown that calcium and Vitamin D supplements seems to
      enhance the rate of bone mineral acquisition, and can play a role in osteoporosis
      prevention. In this paper we review some of the more important questions about
      this condition, its pathogenesis, diagnosis, and prevention.

PMID- 20042381
TI  - Measures of the intergenerational transmission of body mass index between mothers
      and their children in the United States, 1981-2004.
AB  - This research provides estimates of the intergenerational persistence of body
      mass index (BMI) between women and their children when both are at similar stages
      of the lifecycle. Using data from the National Longitudinal Survey of Youth 1979
      (NLSY79) and the Young Adults of the NLSY79, associations between the weight
      status of women and their children are measured when both generations are between
      the ages of 16 and 24. In the entire sample, the measured intergenerational
      correlation of BMI is significantly different from zero and equal to 0.35. This
      result differs by gender with a BMI correlation between female children and their
      mothers of 0.38, compared to a significantly lower BMI correlation of 0.32
      between mothers and their sons. Measures of this relationship across the
      distribution of BMI using quantile regression and quadrant dependence techniques
      indicate that the intergenerational persistence of BMI is strongest at higher
      levels of BMI. Strong dependence across generations is found when categorical
      outcomes of obesity and overweight are implemented. These results provide
      evidence of the strong persistence of weight problems across generations which
      may affect economic mobility within families.

PMID- 20042383
TI  - [Charles Robert Darwin: the great founder of scientific evolutionism].
AB  - Today, we celebrated 200 years since Charles Darwin, one of the world's most
      creative and influential thinkers, was born. And there happens to be the 150th
      anniversary of the publication of his famous book, On the Origin of Species. It
      is verified that On the Origin of Species is an immortal classic book and is
      still guiding the study of anagenesis in life science as the development of
      natural science from then on, and even though most of the ideas in the book are
      well-known at the present age. In the article, we recall the brilliance and
      predomination life of Darwin, a great sage with rich scientific achievements,
      review briefly the novel discoveries and theories after him in the field, and
      then elucidate the focal points and perspectiveas in near future study of
      evolution.

PMID- 20042384
TI  - [Regulation of compaction initiation in mouse embryo].
AB  - Developmental events in preimplantation mouse embryos include the first cleavage,
      the activation of the embryonic genome, the compaction of the blastomeres to form
      morula (MO), and the formation of the blastocyst (BL). Compaction, the first cell
      differentiation event in mammalian development, occurs at the late eight-cell
      stage in the mouse and may be described in terms of some types of morphological
      change, which involve reorganization within a cell and intercellular
      reorganization. Surface microvilli became restricted to a few basal sites and to
      an externally facing (apical) pole. Prior to compaction, the blastomeres are
      spherical and lack specialized intercellular junctions. During compaction, the
      cells were flattened against one another, thus maximizing intercellular contact
      and obscuring intercellular boundaries. It is believed that the events of
      compaction have an important influence on the processes involved in blastocyst
      formation, namely the initiation of inner cell mass and trophectoderm
      differentiation. The inner cell mass will form the future embryo proper, whereas
      the trophectoderm cells will form only extraembryonic tissues. Compaction is
      initiated by E-cadherin mediated cell adhesion, which is regulated post
      translationally via protein kinase C. With E-cadherin knock-out, maternal E
      cadherin is able to mediate the compaction process at the morula stage. Initial
      adhesion is mediated by homophilic interactions between E-cadherin extracellular
      domains.In this review, we attempted to describe this process in detail.

PMID- 20042385
TI  - [ALT--alternative lengthening of telomere].
AB  - The maintenance of the length and normal structure of telomeres is highly related
      to the development of senescence and tumorigenesis. The mechanisms of maintaining
      telomere are essential for cell growth and the reactivation of these mechanisms
      is an important step in tumor progression. The mechanism of telomere maintenance
      might be the reactivation of telomerase. In the case of telomerase deficiency,
      the mechanisms for maintaining the lengths of telomeres are referred to as
      alternative lengthening of telomere (ALT). The characteristics of the ALT cells
      include great heterogeneity of telomere size in individual cells, ALT-associated
      PML (promyelocytic leukemia) bodies, and evident homologous recombination. The
      ALT-related proteins and elevated homologous recombination found in ALT cells
      provide a possible mechanism for the alternative lengthening of telomere. The
      study of ALT provides a new view of crosstalk between senescence and
      tumorigenesis.

PMID- 20042386
TI  - [Advances of microarray analysis on plant gene expression under environmental
      stresses].
AB  - Different stressed conditions impair plant growth and further, cause great loss
      of crop yield and even lead to lose production completely. Increasing
      resistance/tolerance of crops under stressed conditions is a major goal of
      numerous plant breeders, and many elegant works are focusing on this area to
      uncover these complicated mechanisms underlying it. However, the traditional
      strategies including physiological and biochemical methods, as well as studies on
      a few genes, can not well understand the overall biological mechanism. Microarray
      analysis opens a door to uncover these cryptic mechanisms, and has the ability of
      detecting gene transcription and regulation at genomic level in different plant
      tissues. And works in association with related methods of proteomics and
      metabolomics. Therefore, it is possible to locate genes in certain key metabolism
      pathways. Through these procedures, it is also possible to look for critical
      genes in the pathway and to well understand the molecular mechanism of
      resistance/tolerance. These results can be as a guidance for increasing the
      resistance/tolerance of stressed conditions using biotechnology methods in
      future. This paper mainly focused on and discussed the advances of microarray
      analysis of stressed conditions-related genes in plants.

PMID- 20042387
TI  - [Advances in mechanism of small RNAs].
AB  - The discovery of RNA interference (RNAi) heralded a revolution in RNA biology.
      Researchers uncovered 'hidden' layers of regulation of gene expression, in which
      many previously unidentified families of small RNAs (consisting of approximately
      20-30 nucleotides) mediate gene silencing in transcriptional and post
      transcriptional levels. In eukaryotes, these small RNAs, including siRNAs,
      miRNAs, piRNAs, scnRNAs, 21U-RNAs, and some others, regulate gene expression,
      helping to control cellular metabolism, growth, and differentiation, to maintain
      genome integrity, to regulate stem cell renewal, and to combat viruses and mobile
      genetic elements. This review summarizes the current advancement in the
      identification and biosynthesis of small RNAs and their roles in gene regulation.

PMID- 20042388
TI  - [The functions of GLI3 and EN1 genes in idiopathic congenital talipes
      equinovarus].
AB  - To investigate the role of gene Gli3 in idiopathic congenital talipes equinovarus
      (ICTEV), we constructed the Gli3 luciferase reporter gene expression vectors to
      analyze the promoter activity of the rat gene Gli3. The regulatory element in the
      promoter region of the rat Gli3 was predicted using P-Match software and further
      verified by ChIP experiment. Meanwhile, the correlation between the rat En1 and
      ICTEV was evaluated by RT-PCR, immunohistochemistry, and Western blotting
      analyses. The result from P-Match software prediction showed that only one of the
      three possible En1 binding sites in Gli3 promoter region was interacted directly
      with En1 in vivo, which was confirmed by ChIP analysis. The results from RT-PCR,
      immunohistochemistry and Western blotting analyses suggested that En1 was down
      regulated in ICTEV model rats compared to the controls. Our results indicated
      that En1 might be the negative regulatory element in the upstream of Gli3. The
      low expression level of EN1 in ICTEV could contribute to the up-regulation of
      GLI3, which led to the genesis of ICTEV.

PMID- 20042389
TI  - [The polymorphism of bovine POMC gene and its association with the growth traits
      of Nanyang cattle].
AB  - Pro-opiomelanocortin (POMC) plays an important role on animal ingestive behavior
      and energy homeostasis. Genetic variation of POMC was detected by PCR-SSCP and
      DNA sequencing techniques in 480 individuals from seven cattle breeds (i.e.,
      Qinchuan, Nanyang, Jiaxian Red cattle, Jinnan, Luxi, Angus, and Chinese
      Holstein), and association analyses were carried out to evaluate the effects of
      genotypes of the candidate genes on growth traits in Nanyang cattle. Three SNPs
      (811845 C>T, 811821 T>C and 811797 A>G, ref. NW_928357) in linkage were detected
      in P3 locus, which were located at the 3' flanking region of bovine POMC gene.
      The body weight at 6-month-old and the average daily gain of 0~6-month-old were
      higher in Nanyang cattle with the genotype BB than with the genotype AA (P<0.05).

PMID- 20042390
TI  - [Studies of effect of prosaposin on cell proliferation, cell apoptosis and its
      possible molecular mechanism].
AB  - pcDNA3.1 in NIH3T3 and Psap-Myc in NIH3T3 cell strains were used as cell models
      in order to study the effect of prosaposin on cell proliferation, cell apoptosis
      and its possible molecular mechanism. MTT assay and Annexin V/PI apoptosis kit
      were used to detect the effect of prosaposin on cell proliferation and cell
      apoptosis induced by se-rum-starvation stress, respectively. Western blotting was
      conducted to detect the phosphorylative level of PI3K/Akt pathway, and real-time
      PCR was carried out to explore the expression of the genes regulated by PI3K/Akt
      pathway. Prosaposin pro-tein was proved to activate the PI3K/Akt signal pathway,
      upregulate the phosphorylative activity of Akt at Serine 473, downregulate the
      expression of P27(Kip1) gene, upregulate the expression of Cyclin D1 gene and
      then promote the G1/S tran-sition, and upregulate the expression of survival
      genes cIAP1 and cIAP2 and then prevent cell apoptosis. These findings suggest
      that the growth promotion and anti-apoptotic activity of prosaposin may be partly
      through the PI3K/Akt signal pathway and its downstream targeted genes.

PMID- 20042391
TI  - [Isolation, phylogenetic analysis and developmental expression parttern of
      AmphiRab23b in amphioxus].
AB  - The hedgehog (Hh) pathway plays an important role during the embryonic
      development and is related to the progression of cancers. Rab23 is a crucial
      functional molecule in Hh pathway. However, there is no report about amphioxus
      Rab23 up to now except the annotations of two isoforms in the genome of Florida
      lancelet (Branchiostoma floridae). Here a 2062 bp full-length cDNA sequence of
      the Rab23, AmphiRab23b, was isolated from Chinese amphioxus (Branchiostoma
      belcheri), which included the UTRs and an open reading frame of 714 bp, encoding
      a protein of 237 amino acids. Phylogenetic analysis suggested that AmphiRab23b
      falled outside the vertebrate clade. But sequence analysis indicated that this
      putative AmphiRab23b protein contained a specific Rab23_lke domain, which implied
      that Rab23 gene was functional conservative during evolution. And its
      developmental expression pattern showed that AmphiRab23b was expressed in the
      differentiating neural plate and alimentary canal, as the same as the expression
      pattern of the homologous vertebrate genes, which suggested that AmphiRab23b may
      function in the development of nervous system and alimentary canal.

PMID- 20042392
TI  - [Chromosomal localization and development of SNP markers of a serine protease
      gene in Farrer's scallop (Chlamys farreri)].
AB  - Disease control is a main objective in the culture of Farrer's scallop (Chalmys
      farreri). Many investigations have focused on the innate immune system of this
      species. Serine proteases amplify signals in many immune-related pathways and
      thus play a crucial role in innate immune system. Recently, studies on serine
      protease in C. farreri were mainly on sequence analysis and expression profile,
      but no study on gene localization was reported. In this study, a BAC clone
      (CFB040H03) that contains a serine protease gene of C. farreri was located on the
      long arms of a pair of homologous chromosomes by BAC-FISH technique. Six SNPs
      were found inside the serine protease gene using direct sequencing of the PCR
      products. The chromosomal localization of serine protease gene would provide
      fundamental support for further research on this gene. The SNPs obtained can be
      mapped to the genetic linkage map and is helpful to the construction of the
      integration map of C. farreri.

PMID- 20042393
TI  - [Analysis of the aminoacyl-tRNA synthetase genes of silkworm (Bombyx mori)].
AB  - For further research on number, type, composition and origin of Bombyx mori
      aminoacyl-tRNA synthetase (BmaaRS) genes, in silico cloning was performed with
      Bombyx mori genomic and EST databases. There might be two different sets of aaRS
      nuclear gene in Bombxy nori genome, which encode mitochondrial BmaaRS and
      cytoplasmic BmaaRS, respectively. Among BmaaRS genes, there were 2 genes encoding
      mitochondrial BmSerRS, but no genes encoding cytoplasmic BmHisRS and
      mitochondrial BmGlnRS, BmLysRS, BmGlyRS, and BmThrRS. The functions of these
      absent genes could be directly replaced by other proteins with similar functions,
      or might undergo their distinct BmaaRS functions based on the alternative splice
      of one certain BmaaRS mRNA. Evidence of EST indicated that BmaaRS performed
      different alternative splicing patterns. The homology comparison and advanced
      structural analysis of BmaaRS demonstrated the existence of extended domains of
      BmaaRS. This is because some different BmaaRSs contained similar domain.
      Moreover, BmaaRSs with similar functions possessed the similar tertiary
      structure. Phylogenetic analysis revealed that BmaaRS encoded by two various
      sources of BmaaRS genes. Mitochondrial and cytoplasmic BmaaRS had different
      origin.

PMID- 20042394
TI  - [Genetic variation of SNP loci based on candidate gene for resistance to soybean
      cyst nematode].
AB  - For clarifying the difference of genetic diversity and linkage disequilibrium
      (LD) level between cultivated (Glycine max (L.) Merr.) and annual wild soybean
      (Glycine soja Sieb. & Zucc.), genetic variation pattern of 8 SNP loci developed
      from soybean cyst nematode resistance candidate genes rhg1 and Rhg4 in soybean
      germplasm were analyzed. The results indicated that G. max population, consisted
      of cultivated soybean mini-core collection and modern cultivars, had a higher LD
      levels (R2 value is 0.216) than G. soja population. Since 100% of pairwise loci
      within a gene and 16.6% of pairwise loci between genes were significant in G. max
      population, two specific LD regions were formed for each gene. A total of 46
      haplotypes were detected in 363 soybean germplasm. The population of G. soja had
      less number of haplotypes and higher haplotype diversity than the population of
      G. max. Among the 31 population-specific haplotypes, 15 haplotypes were specific
      for G. soja population. In addition, the frequency of two major predominant
      haplotypes (Hap_10 and Hap_11) in G. soja population was obviously decreased in
      G. max population, which might indicate that some new haplotypes were formed and
      some old haplotypes were lost during the G. max domesticated from G. soja.

PMID- 20042395
TI  - [Construction of cDNA library of 'Hongyang' kiwifruit and analysis of F3H
      expression].
AB  - The SMART switching mechanism at 5' end of the RNA transcript technique was used
      to construct a cDNA library from inner pericarp of the red flesh kiwifruit
      Actinidia chinesis cv 'Hongyang'. Construction of cDNA library facilitated
      cloning of the genes associated with the secondary metabolism, the specific genes
      in the course of anthocyanin biosynthesis. The titers of the primary library and
      the amplified library were 6.7x104 cfu/mL and 2.72x108 cfu/mL, respectively. The
      recom-bination rate was over 99.8%. The lengths of most cDNAs in the library
      ranged from 700 bp to 1 000 bp. A total of 1 014 clones randomly chosen from the
      cDNA library were sequenced and these expressed sequence tags (ESTs) were
      analyzed. A set of 963 sequences were obtained. Clustering and assembly of these
      cDNA sequences resulted in 632 unigenes, includ-ing 92 contigs and 540
      singletons. Among them, 441 EST unigenes were predicted to have known functions.
      Gene AcF3H, which participated in anthocyanin biosynthesis from sequencing, was
      obtained. The length of the AcF3H cDNA was 1 369 bp (GenBank accession No:
      FJ542819). Bioinformatic analysis showed that AcF3H ORF region was 1 101 bp,
      which en-coded a peptide with 366 amino acids. The amino acid sequences of this
      gene shared extensive homology to Arabidopsis, Vitis, and Eustoma. The expression
      of AcF3H was investigated in inner pericarp of 'Hongyang' at six stages during
      fruit development using RT-PCR. The expression level was high before colour
      changed stage, and then decreased at the primary stage of pigmentation.

PMID- 20042396
TI  - [A preliminary exploration into the inquiring teaching mode of developmental
      biology].
AB  - Modern developmental biology is changing everyday at a fast pace, and it also
      possesses the most application potential. As an important selected course for
      undergraduates, its most up-to-date knowledge challenges the traditional teaching
      method. We discussed the current situation in developmental biology teaching,
      introduced in detail our method of using original papers in each research area,
      especially the classical papers that won the Nobel Prizes, and summarized the
      advantages of combining students' presentation in the classroom and their
      discussion on the web. We proposed some practical strategies to improve
      developmental biology teaching.

PMID- 20042397
TI  - An unusual cause of hypertension and renal failure: a case series of a family
      with Alagille syndrome.
AB  - Alagille Syndrome (OMIM 118450) is a multisystem developmental disorder inherited
      in an autosomal dominant pattern with variable expression. It commonly manifests
      in children with early cholestatic jaundice due to paucity of interlobular
      biliary ducts. Renal involvement is less common but can take various forms
      including renovascular disease, renal agenesis or hypoplasia, cystic renal
      disease, mesangiolipidosis, tubulointerstitial nephritis and renal tubular
      acidosis. We describe a family of Alagille syndrome with JAG 1 mutation running
      through at least two generations, affecting four members with variable phenotypic
      expressions and disease severity. Alagille syndrome should be considered in the
      differential diagnosis of adults with renovascular disease and children with
      agenesis/dysgenesis of kidney and reflux nephropathy even in the absence of
      hepatic disease. Renal transplant can be successful in these patients although
      living related donation may not be appropriate given the high penetrance and
      variable expression of this condition. This syndrome may cause symptomatic
      bradyarrhythmias as described in our series.

PMID- 20042398
TI  - Intrarenal vascular resistance parameters in kidney transplant patients receiving
      calcineurin inhibitor-based or sirolimus-based regimens.
AB  - BACKGROUND: Use of a calcineurin inhibitor (CNI) immunosuppressant following
      kidney transplantation is associated with development of vasomotor
      nephrotoxicity. This study was undertaken to evaluate and compare the influences
      of CNI-based and CNI-free immunosuppressant regimens on two intrarenal vascular
      resistance parameters, the resistive index (RI) and the pulsatility index (PI),
      in renal transplant recipients. METHODS: Forty-nine renal transplant patients who
      received ultrasonography examination between January 2007 and December 2007 were
      enrolled in this case-control study. Thirty-one subjects received a CNI-based
      regimen, and 18 received a CNI-free (sirolimus-based) regimen. RI and PI were
      determined by duplex Doppler ultrasonography. RESULTS: Patients receiving a CNI
      displayed lower cholesterol and triglyceride values and higher RI (mean: 0.7 vs.
      0.6, P = 0.002) and PI values (mean: 1.3 vs. 1.1, P = 0.034). Multivariate
      analyses revealed that advanced age and use of alpha-blockers or diuretics were
      modestly associated with higher RI and PI values. By multivariate analysis, use
      of sirolimus was associated with a lower RI by -0.05 [95% confidence interval
      (CI): -0.085, -0.019; P = 0.003] but not with a lower PI (95% CI: -0.245, 0.001;
      P = 0.053). CONCLUSIONS: Use of sirolimus is only modestly correlated with a
      reduced RI and is not associated with a reduced PI. These observations question
      the superiority of CNI-free over CNI-based regimens with regard to reduction of
      intrarenal vascular resistance post-transplantation. These findings combined with
      those regarding recipient factors also cast doubt on the specificity of
      intrarenal resistance indices for predicting allograft function and/or survival.

PMID- 20042399
TI  - Rapidly progressive glomerulonephritis complicating primary AL amyloidosis and
      multiple myeloma.
AB  - Crescentic glomerulonephritis is a rare complication of AA amyloidosis. There are
      no clinical case reports of this complicating AL amyloidosis. A 67-year-old man
      developed rapidly progressive glomerulonephritis (RPGN) on a background of
      primary AL amyloidosis and IgGkappa multiple myeloma. Investigations for causes
      of glomerulonephritis were negative, and a renal biopsy confirmed crescentic
      glomerulonephritis and amyloid deposition. He progressed to end stage kidney
      disease (ESKD) requiring dialysis after 2 months and died 7 months after
      diagnosis after further treatment of multiple myeloma failed to arrest
      progression. We believe this to be the first clinical case report of RPGN
      complicating primary (AL) renal amyloidosis and multiple myeloma.

PMID- 20042400
TI  - Omacor, n-3 polyunsaturated fatty acid, attenuated albuminuria and renal
      dysfunction with decrease of SREBP-1 expression and triglyceride amount in the
      kidney of type II diabetic animals.
AB  - BACKGROUND: We assumed that n-3 polyunsaturated fatty acid (n-3 PUFA) would
      attenuate the tissue dyslipidemic condition through suppression of sterol
      regulatory element-binding protein (SREBP-1) in the kidney and would prevent
      renal progression in diabetic animals. METHODS: We gavaged Omacor, composed of
      docosahexaenoic acid and eicosapentaenoic acid, to db/db mice for 2 weeks (0.2
      g/100 g/day). We measured the markers of renal function, triglyceride amount and
      expressions of SREBP-1, liver X-activated receptor alpha (LXRalpha), collagen IV
      and TGFbeta-1 in kidney lysate, and performed immunohistochemical staining for
      SREBP-1, desmin and WT-1 in the renal sections. We measured collagen IV in
      primary mesangial cells cultured with high glucose media (25 mM), both with and
      without a transient transfection of small interfering RNA (siRNA) SREBP-1.
      RESULTS: Omacor decreased the concentration of serum free fatty acid, and the
      amount of renal triglyceride, which was associated with decreased expression of
      SREBP-1 in the kidney, albuminuria and renal dysfunction in db/db mice. Omacor
      attenuated the expansion of mesangial matrix and the expression of desmin,
      preserved the WT-1 positive cells, and inhibited the phosphorylation of nuclear
      factor kappaB in renal tissue. In mesangial cells cultured in high glucose media,
      the suppression of SREBP-1 expression decreased the collagen IV in the cells.
      CONCLUSIONS: Our study results demonstrated that n-3 PUFA prevented renal
      progression with attenuation of SREBP-1 and reduction of triglyceride in the
      diabetic kidney. This suggests that the regulation of dyslipidemic signals in the
      kidney could be a possible mechanism by which PUFA preserves renal function in
      the diabetic condition.

PMID- 20042401
TI  - SCUBE1, a novel developmental gene involved in renal regeneration and repair.
AB  - BACKGROUND: We have identified that a novel developmental gene and protein,
      SCUBE1, is expressed in endothelial cells and may play an important role in
      kidney regeneration. METHODS: The temporal and spatial expression of SCUBE1 was
      determined in a mouse model of ischaemia-reperfusion (IR) injury at 3 days and 1,
      3 and 6 weeks post-injury by immunofluorescence microscopy. In vitro analysis was
      used to examine SCUBE1 signalling in endothelial cells under conditions of cell
      stress using quantitative real-time polymerase chain reaction and
      immunofluorescence labelling. The media from cultured endothelial cells following
      SCUBE1 small interfering RNA (siRNA) transfection was used to assess the
      proliferation capacity of epithelial cells. RESULTS: Immunofluorescence confocal
      microscopy demonstrated that the SCUBE1 protein was localized to CD31-positive
      endothelial cells in IR kidneys during the resolution of tissue damage (3 weeks),
      but not in control animals. The peak expression of SCUBE1 following 3 weeks of IR
      injury was confirmed by reverse transcription-polymerase chain reaction. SCUBE1
      mRNA and protein expression were detected in cultured endothelial cells under
      hypoxic conditions or serum starving. Furthermore, there was a significant
      decrease in epithelial cell proliferation following the addition of a supernatant
      derived from cultured endothelial cells following SCUBE1 siRNA gene silencing
      compared to control media. CONCLUSIONS: Our results indicate that SCUBE1 may be
      involved in the regulation of tubular cell proliferation and re-epithelialization
      during the resolution of kidney injury.

PMID- 20042402
TI  - Hypertension after kidney transplantation: still a SECRET?

PMID- 20042403
TI  - A critical review of the literature: engendering the discourse of masculinities
      matter for parenting African refugee men.
AB  - According to the literature on culturally and linguistically diverse parenting,
      refugee parenting practices and styles that are normative in countries of origin
      may not be sanctioned in Australia. In the case of refugee parenting, beliefs,
      practices, and values may be decentered in pre-resettlement contexts where
      survival becomes the primary concern. Engendering the discourse of masculinities
      to reflect a relationship between child protection and the experience of refugee
      parenting for African men in both pre- and post-resettlement contexts will inform
      culturally competent practice, intervention, and community development that is
      inclusive of their gender-specific needs. This article brings an expanded
      masculinities perspective to the ecology of refugee parenting for resettled
      African men resulting from larger research findings with focus group
      participants. Incorporating notions of masculinity into the child protection
      discourse is an attempt not only to reduce existing gender under- and
      misrepresentation among South Australian refugees but also to ensure greater
      visibility and increase the role of refugee men in the process of developing
      culturally relevant and appropriate policies, practices, and services to assist
      successful resettlement transitions while strengthening family well-being. The
      concept of masculinities, this article argues, must be treated as integral to any
      approach to working with refugees, particularly in areas that penetrate and may
      define the quality of their life experiences, expectations, and aspirations.
      Masculinities matter. Exploring refugee male perceptions, interpretations, and
      enactment of masculinity may unmask the differential experiences of refugee women
      from men and ensure the integration and operationalization of these differences
      into child protection services and practice.

PMID- 20042404
TI  - Granulosa cell tumor of the broad ligament: report of a case with emphasis on the
      differential diagnosis with female adnexal tumor of probable Wolffian origin.
AB  - This is a report of a paratubal adult granulosa cell tumor (GCT) located within
      the right broad ligament in a 62-year-old woman. These are rare tumors with only
      8 cases reported so far. Because of an overlap of topographic, morphologic, and
      immunohistochemical features, it is not always possible to differentiate between
      the broad ligament GCT and female adnexal tumor of probable Wolffian origin
      (FATWO). Although nuclear grooving is not an exclusive feature of GCT and can be
      seen in a variety of other neoplasms, in the context of the differential
      diagnosis between broad ligament GCT and FATWO, the presence of this feature may
      be very useful in establishing the diagnosis of broad ligament GCT.

PMID- 20042405
TI  - Florid capsular and pericapsular papillary endothelial proliferation associated
      with poorly differentiated thyroid carcinoma.
AB  - Papillary endothelial hyperplasia (PEH) occurring within or around the capsule of
      thyroid neoplasms is rare. Such Masson-like lesions, which have been attributed
      to fine needle aspiration-induced injury and thrombosis, can mimic tumor
      angioinvasion or vascular neoplasms. This study reports the case of a poorly
      differentiated carcinoma of the thyroid that was accompanied by more than 10 foci
      of pericapsular and peritumoral papillary endothelial hyperplasia, one of which
      contained a tumor embolus. The vessels within the papillary fronds had CD31- and
      CD34-staining blood vessels but were lined by D2-40 staining endothelial cells,
      which were continuous with the lining of the spaces within which PEH had
      developed. This suggests that, in contrast to Masson's lesions that develop
      within blood vessels as a result of thrombosis, pericapsular PEH associated with
      thyroid neoplasms develops within lymphatics, possibly related to lymphangiogenic
      factors secreted by the thyroid neoplasms.

PMID- 20042406
TI  - Can the therapeutic gain of radiotherapy be increased by concurrent
      administration of Asian botanicals?
AB  - Therapeutic gain by radiotherapy can be achieved through improved targeting,
      selectively sensitizing malignant cells, or protecting normal tissue. The
      majority of synthetic chemical radiation sensitizers and normal tissue protectors
      have proved to be too toxic at effective clinical doses. However, Asian
      botanicals (from both Chinese and Ayurvedic medicine) are being evaluated for
      their ability to improve therapeutic gain through the modulation of reactive
      oxygen species. An increase in the efficacy of radiotherapy on tumor tissue
      allows a reduction in the dose applied to normal tissues. In addition, some
      botanicals may selectively protect normal tissue or increase its repair following
      radiation therapy. The results are promising enough to consider clinical trials.

PMID- 20042407
TI  - In this issue: circadian disruption and cancer.

PMID- 20042408
TI  - Circadian disruption in experimental cancer processes.
AB  - The circadian timing system (CTS) coordinated by the suprachiasmatic nuclei (SCN)
      of the hypothalamus regulates daily rhythms of behavior, physiology, as well as
      cellular metabolism and proliferation. Altered circadian rhythms predict for poor
      survival in cancer patients. An increased incidence of several cancers has been
      reported in flight attendants and in shift workers. To explore the contribution
      of the CTS to tumor growth, we developed experimental models of disrupted or
      enhanced circadian coordination through stereotaxic destruction of the SCN,
      modifications of photoperiodic or feeding synchronizers and/or the administration
      of pharmacologic agents. SCN ablation or exposure to experimental chronic jetlag
      (CJL, consisting of an 8-hour advance of the light-dark cycle every 2 days)
      caused alterations in circadian physiology and significantly accelerated tumor
      growth. CJL suppressed or altered the rhythms of clock gene and cell cycle gene
      expression in mouse liver. It increased p53 and decreased c-Myc expression, a
      result in line with the promotion of diethylnitrosamine -initiated
      hepatocarcinogenesis in jet-lagged mice. The accelerating effect of CJL on tumor
      growth was counterbalanced by the regular timing of food access over the 24-h.
      Meal timing prevented the circadian disruption produced by CJL and slowed down
      tumor growth. In synchronized mice, meal timing reinforced host circadian
      coordination, phase-shifted the transcriptional rhythms of clock genes in the
      liver of tumor-bearing mice and slowed down cancer progression. These results
      support the role of the CTS in cancer progression and call for the development of
      therapeutic strategies aimed at preventing or treating circadian clock
      dysfunctions.

PMID- 20042409
TI  - Clock genes and cancer.
AB  - Period genes ( Per2, Per1) are essential circadian clock genes. They also
      function as negative growth regulators. Per2 mutant mice show de novo and
      radiation-induced epithelial hyperplasia, tumors, and an abnormal DNA damage
      response. Human tumors show Period gene mutations or decreased expression. Other
      murine clock gene mutations are not associated with a tumor prone phenotype.
      Shift work and nocturnal light exposure are associated with circadian clock
      disruption and with increased cancer risk. The mechanisms responsible for the
      connection between the circadian clock and cancer are not well defined. We
      propose that circadian disruption per se is not uniformly tumor promoting and the
      mechanisms for tumor promotion by specific circadian clock disturbances will
      differ dependent upon the genes and pathways involved. We propose that Period
      clock gene mutations promote tumorigenesis by unique molecular pathways. Per2 and
      Per1 modulate beta-catenin and cell proliferation in colon and non-colon cancer
      cells. Per2 mutation increases intestinal beta-catenin levels and colon polyp
      formation. Per2 mutation also increases Apc(Min/+)-mediated intestinal and
      colonic polyp formation. Intestinal tumorigenesis per se may also alter clock
      function as a result of increased beta-catenin destabilizing PER2 protein. Levels
      and circadian rhythm of PER2 in Apc(Min/+) mouse intestine are markedly
      decreased, and selective abnormalities in intestinal clock gene and clock
      controlled gene expression are seen. We propose that tumor promotion by loss of
      PERIOD clock proteins is unique to these clock genes as a result of altered beta
      catenin signaling and DNA damage response. PERIOD proteins may offer new targets
      for cancer prevention and control.

PMID- 20042410
TI  - Circadian stage-dependent inhibition of human breast cancer metabolism and growth
      by the nocturnal melatonin signal: consequences of its disruption by light at
      night in rats and women.
AB  - The circadian production of melatonin by the pineal gland during the night
      provides an inhibitory signal to tissue-isolated steroid receptor SR+ and - MCF-7
      human breast cancer xenografts in female nude rats. A pivotal mechanism for
      melatonin's anticancer effects in vivo involves a melatonin receptor-mediated
      inhibition of linoleic acid (LA) uptake and its metabolism to mitogenically
      active 13-hydroxyoctadecadienoic acid (13-HODE). Exposure of (SR-) xenograft
      bearing rats to increasing intensities of polychromatic white light at night
      suppresses melatonin while increasing tumor growth rates, DNA content,
      [3H]thymidine incorporation into DNA, LA uptake, 13-HODE formation, cAMP levels
      and ERK1/2 activation a dose-dependent manner. Similar effects occur in SR- human
      breast cancer xenografts perfused in situ with melatonin-depleted blood from
      healthy female subjects after their exposure to a single bright intensity (2800
      lux) of polychromatic light at night. Additionally, SR- human breast cancer
      xenografts exhibit robust circadian rhythms of LA uptake, 13-HODE formation and
      proliferative activity. Exposure of xenograft-bearing rats to dim light at night
      results in the complete elimination of these rhythms which culminates in
      unfettered, high rates of tumor metabolism and growth. The organization of tumor
      metabolism and growth within circadian time structure by the oncostatic melatonin
      signal helps create a balance between the cancer and its host that is disrupted
      by host exposure to light at night. This biological mechanism may partially
      explain the higher risk of breast and other cancers in women working rotating
      night shifts and possibly others who also experience prolonged exposure to light
      at night.

PMID- 20042411
TI  - Light-mediated perturbations of circadian timing and cancer risk: a mechanistic
      analysis.
AB  - In industrialized countries, certain types of cancer, most notably, breast and
      prostate, are more frequent than in poorly developed nations. This high cancer
      frequency is not explained by any of the conventional causes. Within the past
      decade, numerous reports have appeared that link light at night with an elevated
      cancer risk. The three major consequences of light at night are sleep
      deprivation, chronodisruption, and melatonin suppression. Each of these
      individually or in combination may contribute to the reported rise in certain
      types of cancer. In this article, the potential mechanisms underlying the basis
      of the elevated cancer risk are briefly discussed. Finally, if cancer is a
      consequence of excessive nighttime light, it is likely that other
      diseases/conditions may also be exaggerated by the widespread use of light after
      darkness onset.

PMID- 20042412
TI  - Making circadian cancer therapy practical.
AB  - Practical circadian therapy for the cancer patient involves 3 spheres of
      intervention-improving lifestyle, optimizing internal biochemical milieu, and
      adjusting treatment times. The potential value of improving overall circadian
      functioning is shown in the work of Mormont et al in which pronounced rest
      activity rhythms were associated with better survival in colorectal cancer
      patients receiving chronomodulated chemotherapy. Lifestyle interventions that may
      improve circadian functioning involve diet, physical activity, and mind-body
      therapies. A diet that is anti-inflammatory and has appropriate carbohydrate
      intake, as well as regular meal timing, encourages normal circadian cycles.
      Adequate daytime physical activity encourages restful sleep, and morning light
      exposure during exercise may entrain melatonin rhythms. Meditation and other mind
      body therapies can reduce anxiety and depression that may disrupt sleep. Aspects
      of the biochemical milieu that specifically disrupt circadian functioning are
      inflammation and stress hormones. Inflammation and cytokine disruption can be
      addressed with diet, herbs, and other natural substances. Chronomodulation of
      chemotherapy in a US clinical setting will be discussed. A series of 12 cases
      will be presented of patients who experienced grade 3 to 4 toxicities with
      various chemotherapy regimens for colorectal cancer. When rechallenged with the
      same regimens administered chronotherapeutically, none of the patients
      experienced grade 3 to 4 toxicity. Integrating all the above treatment modalities
      has the potential to improve both the quality of life and disease outcomes in
      cancer patients.

PMID- 20042413
TI  - Nutrition and orthomolecular supplementation in lung cancer patients.
AB  - This article reviews updates and provides some data related to nutritional and
      orthomolecular supplementation in oncology patients with an emphasis on lung
      cancer, a commonly diagnosed tumor with significant nutritional disturbances.
      Cancer and its treatment play a significant role in nutritional imbalance which
      likely has negative impact on the patient both in terms of quality and quantity
      of life. Nutritional supplementation may correct these imbalances with
      significant clinical benefit both physiologically and psychologically. This
      review will help assist in providing clinically useful data to assess the cancer
      patient's nutritional status and to guide nutritional intervention to assist
      these patients' recovery.

PMID- 20042414
TI  - Revisiting the ALA/N (alpha-lipoic acid/low-dose naltrexone) protocol for people
      with metastatic and nonmetastatic pancreatic cancer: a report of 3 new cases.
AB  - The authors, in a previous article, described the long-term survival of a man
      with pancreatic cancer and metastases to the liver, treated with intravenous
      alpha-lipoic acid and oral low-dose naltrexone (ALA/N) without any adverse
      effects. He is alive and well 78 months after initial presentation. Three
      additional pancreatic cancer case studies are presented in this article. At the
      time of this writing, the first patient, GB, is alive and well 39 months after
      presenting with adenocarcinoma of the pancreas with metastases to the liver. The
      second patient, JK, who presented to the clinic with the same diagnosis was
      treated with the ALA/N protocol and after 5 months of therapy, PET scan
      demonstrated no evidence of disease. The third patient, RC, in addition to his
      pancreatic cancer with liver and retroperitoneal metastases, has a history of B
      cell lymphoma and prostate adenocarcinoma. After 4 months of the ALA/N protocol
      his PET scan demonstrated no signs of cancer. In this article, the authors
      discuss the poly activity of ALA: as an agent that reduces oxidative stress, its
      ability to stabilize NF(k)B, its ability to stimulate pro-oxidant apoptosic
      activity, and its discriminative ability to discourage the proliferation of
      malignant cells. In addition, the ability of lowdose naltrexone to modulate an
      endogenous immune response is discussed. This is the second article published on
      the ALA/N protocol and the authors believe the protocol warrants clinical trial.

PMID- 20042415
TI  - Four-year follow-up of endograft repair of traumatic aortic transection in a 10
      year-old.

PMID- 20042416
TI  - Identifying the unauthorized use of examination material.
AB  - Item disclosure is one of the most serious threats to the validity of high stakes
      examinations, and identifying examinees that may have had unauthorized access to
      material is an important step in ensuring the integrity of an examination. A
      procedure was developed to identify examinees that potentially had unauthorized
      prior access to examination content. A standardized difference score is created
      by comparing examinee ability estimates for potentially exposed items to ability
      estimates for unexposed items. Outliers in this distribution are then flagged for
      further review. The steps associated with this procedure are described and
      followed by an example of applying the procedure. In addition, the use of this
      procedure is supported by the results of a simulation that models the use of
      unauthorized access to examination material.

PMID- 20042417
TI  - The role of pharmacists in smoking cessation in Poland.
AB  - In Poland, 38.0% of men and 25.6% of women smoke daily. One method for expanding
      access to smoking cessation services is through community-based pharmacists.
      Surveys were administered in 2007-2008 to (a) current smokers, (b) members of a
      pharmacy association, and (c) pharmacy students in their final year of training.
      Pharmacists were the highest ranked health professionals to whom Polish smokers
      reported they would turn for information about pharmacological support for
      smoking cessation. Most pharmacists (79%) reported their knowledge allowed them
      to provide basic smoking cessation information to their patients. Pharmacy
      students reported being more able to provide information about the health
      consequences of tobacco smoking than to help patients quit smoking (85% vs. 61%).
      In Poland, community-based pharmacists are positioned to provide smoking
      cessation interventions to all segments of the population. To extend and promote
      smoking cessation efforts, comprehensive tobacco cessation training should be a
      required component of the pharmacy school curriculum.

PMID- 20042419
TI  - Specialist nursing framework for New Zealand: a missing link in workforce
      planning.
AB  - The current global nursing shortage challenges the provision of a well qualified
      and sustainable health workforce to meet future population health needs. An
      identified area of concern for New Zealand reaching health policy targets in
      chronic conditions management and primary health care is an adequate specialist
      nurse workforce supply. This article explores the New Zealand context
      underpinning this concern and contends that effective workforce planning would be
      supported by the development of a single unified framework for specialist nursing
      practice in New Zealand. A consistent national framework has the potential to
      support accurate data collection and enable service providers to identify and
      plan transparent and transferable pathways for specialist nursing service
      provision and development. Advanced practice nursing frameworks assist in
      increasing productivity through building an evidence base about advanced
      practice, enhancing consistency and equity of expertise; supporting a reduction
      in role duplication; and enabling succession planning and sustainability.

PMID- 20042418
TI  - Single-institutional 22 years experience on cardiac myxomas.
AB  - Myxomas are the most common benign tumors of the heart. This study presents
      single-institutional 22 years experience on cardiac myxomas. The records of 9756
      consecutive cases of open heart surgery between 1985 and 2007 revealed 0.23%
      myxoma. Age ranged between 12 and 77 years and male to female ratio was 7:17.
      Myxomas originated from the left atrium (15 patients), mitral valve (3 patients),
      right atrium (2 patients), right atrium and right ventricle (2 patients), right
      ventricle (1 patient), and left ventricle (1 patient). Three patients were
      operated for multiple myxomas. Myxomas were resected through right atriotomy,
      right atriotomy and pulmonary arteriotomy, left atriotomy, biatrial approach, or
      left ventriculotomy depending on the tumor location. Mean follow-up time was 11.5
      years. Mortality occurred in 6 patients (1 early, 5 late deaths). No myxoma
      recurrence was detected. Myxomas should be resected leaving no remnant mass,
      without delay when they are diagnosed.

PMID- 20042420
TI  - Atypical takotsubo cardiomyopathy associated with nasal packing for paranasal
      sinus surgery.
AB  - Takotsubo cardiomyopathy (TC) is characterized by reversible left ventricular
      (LV) apical ballooning and no significant coronary artery stenosis. New variants
      of TC with localized wall motion abnormality or inversed pattern with
      hyperdynamic apex have been reported. We present the case of a 24-year-old female
      with atypical presentation of TC occurring in the setting of paranasal sinus
      surgery under local anaesthesia with post-surgical nasal packing. She did not
      demonstrate ST-segment elevation on electrocardiogram, but transient moderate LV
      systolic dysfunction and localized wall motion abnormality affecting basal to mid
      ventricular anterior and anteroseptal wall. She rapidly and completely recovered
      without sequelae.

PMID- 20042421
TI  - Validation of a novel automated border-detection algorithm for rapid and accurate
      quantitation of left ventricular volumes based on three-dimensional
      echocardiography.
AB  - AIMS: To assess the accuracy and reproducibility of a novel automated software
      for left ventricular (LV) volumes and ejection fraction (EF) measurements using
      real-time three-dimensional echocardiography (3DE). METHODS AND RESULTS: A total
      of 103 patients with a wide range of LV volumes were analyzed with both 4D
      AutoLVQ and 4D TomTec software. In 23 patients, a side-by-side comparison of LV
      volume and EF measurements was done between 3DE, 2DE, and cardiac magnetic
      resonance (CMR). Excellent correlation was found between 4D AutoLVQ and 4D TomTec
      [r = 0.98 for end-diastolic volume (EDV), 0.99 for end-systolic volume (ESV), and
      0.97 for EF, P < 0.0001], with small biases and narrow limits of agreement: EDV
      5.2 mL (-14 to 25 mL), ESV 2.9 mL (-10 to 16 mL), EF -0.2% (-7 to 6%). Time of
      analysis was halved using 4D AutoLVQ with manual correction (1 min 52 s+/- 30 s)
      in comparison with 4D TomTec software (3 min 46 s +/- 1 min 24 s). Both softwares
      showed similar accuracy in comparison with CMR (4D AutoLVQ biases -11.0 mL, -9.1
      mL, and 2.9%; 4D TomTec biases -8.3 mL, -7.4 mL, and 2.8% for EDV, ESV, and EF,
      respectively, P = NS for all) and good reproducibility. CONCLUSION: Novel 4D
      AutoLVQ software showed very good agreement with more time-consuming 4D TomTec
      software, having similar accuracy against CMR.

PMID- 20042422
TI  - Usefulness of trans-oesophageal echocardiography using intracardiac echography
      probe in guiding patent foramen ovale percutaneous closure.
AB  - AIMS: To evaluate the use of intracardiac echocardiography probe through
      oesophageal route (ICE-TEE) for the monitoring of percutaneous foramen ovale
      (PFO) closure procedure. METHODS AND RESULTS: The study was conducted in 50
      patients divided into two groups: in group I (n = 24), accuracy of ICE-TEE in
      assessing the inter-atrial septum (IAS) was compared with standard TEE, and in
      group II, we used ICE-TEE to monitor 26 consecutive patients referred for PFO
      closure. In group I, IAS was constantly visualized with a close correlation
      between ICE-TEE and standard TEE for IAS excursion (r = 0.9, P < 0.0001). In
      group II, ICE-TEE allowed to rule out four patients (three without PFO and one
      with septal atrial defect associated) and identified three complications during
      PFO closure procedure (pericardial effusion, inadequate device deployment, and
      cardiac thrombus). Finally, device implantation was successfully performed in the
      22 patients with no residual shunt and thrombus observed after 3 months.
      CONCLUSION: ICE-TEE could be used to monitor PFO closure procedure.

PMID- 20042423
TI  - A new model of home-based telemonitored cardiac rehabilitation in patients with
      heart failure: effectiveness, quality of life, and adherence.
AB  - AIMS: Despite proven benefits of cardiac rehabilitation (CR), currently proposed
      CR models are not acceptable for many heart failure (HF) patients. The purpose of
      this study was to evaluate a new model of home-based telemonitored cardiac
      rehabilitation (HTCR) using walking training compared with an outpatient-based
      standard cardiac rehabilitation (SCR) using interval training on a cycle
      ergometer. METHODS AND RESULTS: The study included 152 HF patients (aged 58.1 +
      or - 10.2 years, NYHA class II and III, ejection fraction < or = 40%) who were
      randomized to HTCR (n = 77) or SCR (n = 75). All patients underwent 8 weeks of
      CR. Both groups were comparable in terms of demographic and clinical
      characteristics and medical therapy. The effectiveness of CR was assessed by
      changes in NYHA class, peak oxygen consumption, 6-min walking test distance, and
      SF-36 score. Cardiac rehabilitation resulted in a significant improvement of all
      parameters in both groups. All patients in the HTCR group completed the 8 weeks
      of CR, whereas 15 patients in the SCR group (20%) discontinued CR. CONCLUSION: In
      patients with HF, HTCR is equally as effective as SCR and provides a similar
      improvement in quality of life. Adherence to CR seems to be better for HTCR. Home
      based telemonitored cardiac rehabilitation may be a useful alternative form of CR
      in patients with HF.

PMID- 20042424
TI  - Bone marrow cell transplantation improves cardiac, autonomic, and functional
      indexes in acute anterior myocardial infarction patients (Cardiac Study).
AB  - AIMS: Bone marrow (BM) stem cells improve cardiac function and outcome after
      acute ST-segment elevation myocardial infarction (MI). In this randomized
      controlled trial, the effects of intracoronary transfer of autologous BM cells on
      left ventricular ejection fraction (LVEF) and volumes (2D-echo and resting
      SPECT), stroke volume [impedance cardiography (ICG)], autonomic control [heart
      rate variability (HRV)], baroreflex sensitivity (BRS), and exercise tolerance
      (cardiopulmonary exercise test) were assessed in post-MI patients. Exercise
      stress SPECT was also performed. METHODS AND RESULTS: After percutaneous coronary
      intervention (PCI), 38 patients with residual LV dysfunction were randomized to
      either the BM group (optimized treatment plus intracoronary transfer of
      autologous BM cells 4 + or - 1 days after PCI, n = 19) or control (C) group
      (optimized treatment only, n = 19). After 12 months, mean LVEF (%) increased 13.1
      + or - 1.9 in the BM patients vs. 5.3 + or - 2.0 in C, with an increase in stroke
      volume (mL, 14.5 + or - 4.0 in BM vs. 1.8 + or - 3.7 in C) associated with
      improved HRV [SD (ms) 62.4 + or - 8.3 in BM vs. 19.0 + or - 7.5 in C), higher BRS
      (ms/mmHg, 8.0 + or - 1.8 in BM vs. -1.9 + or - 1.7 in C), and peak VO(2) (mL/kg
      min(-1), 3.5 + or - 1.0 in BM vs. -0.4 + or - 0.5 in C). Stress SPECT showed
      improvements in perfusion, regional and global LV function scores (P < 0.05 BM
      vs. C groups for all comparisons). Cell transfer did not increase the risk of
      adverse clinical, in-stent restenosis, or proarrhythmic events. CONCLUSION: The
      beneficial effect of autologous BM cells in post-MI patients with depressed LV
      function may be mediated by restoration of autonomic control, and improved
      exercise tolerance.

PMID- 20042425
TI  - Clinical trials update from the Heart Failure Society of America Meeting 2009:
      FAST, IMPROVE-HF, COACH galectin-3 substudy, HF-ACTION nuclear substudy, DAD-HF,
      and MARVEL-1.
AB  - This article presents findings and a commentary on late-breaking trials presented
      during the meeting of the Heart Failure Society of America in September 2009.
      Unpublished reports should be considered as preliminary, since analyses may
      change in the final publication. The FAST trial showed somewhat better
      performance of intrathoracic impedance for prediction of deterioration in
      patients with heart failure (HF) when compared with daily weighing. The IMPROVE
      HF study reported the benefits of education on the management of patients with
      systolic HF. Galectin-3 appeared a useful method for improving risk
      stratification of patients with chronic HF in a substudy of the COACH trial. A
      nuclear substudy of the HF-ACTION trial failed to demonstrate that resting
      myocardial perfusion imaging, a measure of myocardial scar and viability, was
      clinically useful. A small randomized controlled trial (DAD-HF) suggested that
      the use of low-dose dopamine in patients with acutely decompensated HF was
      associated with less deterioration in renal function and less hypokalaemia. The
      MARVEL-1 trial raises further concerns about the safety of myoblast
      transplantation in ischaemic HF.

PMID- 20042426
TI  - Haemodialysis, not ultrafiltration, can correct hyponatraemia in heart failure.

PMID- 20042428
TI  - Acellular dermal matrix seeded with autologous fibroblasts improves wound
      breaking strength in a rodent soft tissue damage model in neoadjuvant settings.
AB  - Soft tissue defects following resectional surgery or trauma often result in
      deadspaces and require free or pedicled flaps. A programmed formation of filling
      tissue with enhanced biomechanical properties could be helpful. This study
      examined the effects on wound healing of acellular dermal matrix (ADM) seeded
      with autologous fibroblasts in a standardized rodent model. As pre- or
      postoperative radiotherapy is standard in many treatments of malignancies, we
      also investigated the effects of additional radiotherapy. Fischer rats were
      randomised and received a standardized unilateral soft tissue defect at the
      buttock. The defect was filled with ADM+fibroblasts or ADM alone. Controls
      received no filling. Either no radiation, adjuvant (postoperative) or neoadjuvant
      (preoperative) radiation was applied to the defect site. Six weeks later the
      defect volume was measured by MR-tomography. Wound breaking strength was examined
      by tensiometry according to German Industrial Standards. Filling of the defect
      side was significantly larger in ADM and ADM+fibroblast treated groups compared
      to the control group in all settings. Wound breaking strength in the unimodal
      setting was significantly improved in the ADM+fibroblasts group compared to the
      ADM group. In the neoadjuvant setting there was no significant difference between
      control and ADM group. However, the ADM+fibroblasts groups showed a significantly
      increased wound breaking strength compared to the control and the ADM-alone
      group. Seeded or unseeded ADM is able to fill deadspace in this rodent model in
      all settings. Implanting non-irradiated, vital, proliferating autologous
      fibroblasts on ADM results in significantly increased wound breaking strength.

PMID- 20042429
TI  - Design and dynamic culture of 3D-scaffolds for cartilage tissue engineering.
AB  - Engineered scaffolds for tissue-engineering should be designed to match the
      stiffness and strength of healthy tissues while maintaining an interconnected
      pore network and a reasonable porosity. In this work, we have used 3D-plotting
      technique to produce poly-L-Lactide macroporous scaffolds with two different pore
      sizes. The ability of these macroporous scaffolds to support chondrocyte
      attachment and viability were compared under static and dynamic loading in vitro.
      Moreover, the 3D-plotting technique was combined with porogen-leaching, leading
      to macro/microporous scaffolds, so as to examine the effect of microporosity on
      the level of cell attachment and viability under similar loading condition.
      Canine chondrocytes' cells were seeded onto the scaffolds with different
      topologies, and the constructs were cultured for up to 2 weeks under static
      conditions or in a bioreactor under dynamic compressive strain of 10% strain, at
      a frequency of 1 Hz. The attachment and cell growth of chondrocytes were examined
      by scanning electron microscopy and by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. A significant difference in cell attachment was
      observed in macroporous scaffolds with different pore sizes after 1, 7, and 14
      days. Cell viability in the scaffolds was enhanced with decreasing pore size and
      increasing microporosity level throughout the culture period. Chondrocyte
      viability in the scaffolds cultured under dynamic loading was significantly
      higher (p<0.05) than the scaffolds cultured statically. Dynamic cell culture of
      the scaffolds improved cell viability and decreased the time of in vitro culture
      when compared to statically cultured constructs. Optimizing the culture
      conditions and scaffold properties could generate optimal tissue/constructs
      combination for cartilage repair.

PMID- 20042427
TI  - Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3 subunit
      associated with a case of idiopathic ventricular fibrillation.
AB  - AIMS: Loss-of-function mutations in the SCN5A-encoded sodium channel SCN5A or
      Nav1.5 have been identified in idiopathic ventricular fibrillation (IVF) in the
      absence of Brugada syndrome phenotype. Nav1.5 is regulated by four sodium channel
      auxiliary beta subunits. Here, we report a case with IVF and a novel mutation in
      the SCN3B-encoded sodium channel beta subunit Navbeta3 that causes a loss of
      function of Nav1.5 channels in vitro. METHODS AND RESULTS: Comprehensive open
      reading frame mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, GPD1L,
      four sodium channel beta subunit genes (SCN1-4B), and targeted scan of RYR2 was
      performed. A novel missense mutation, Navbeta3-V54G, was identified in a 20-year
      old male following witnessed collapse and defibrillation from VF. The ECG
      exhibited epsilon waves, and imaging studies demonstrated a structurally normal
      heart. The mutated residue was highly conserved across species, localized to the
      Navbeta3 extracellular domain, and absent in 800 reference alleles. We found that
      HEK-293 cells had endogenous Navbeta3, but COS cells did not. Co-expression of
      Nav1.5 with Navbeta3-V54G (with or without co-expression of the Navbeta1 subunit)
      in both HEK-293 cells and COS cells revealed a significant decrease in peak
      sodium current and a positive shift of inactivation compared with WT. Co
      immunoprecipitation experiments showed association of Navbeta3 with Nav1.5, and
      immunocytochemistry demonstrated a dramatic decrease in trafficking to the plasma
      membrane when co-expressed with mutant Navbeta3-V54G. CONCLUSION: This study
      provides molecular and cellular evidence implicating mutations in Navbeta3 as a
      cause of IVF.

PMID- 20042430
TI  - Drug release from PLGA microspheres attached to solids using supercritical CO2.
AB  - Functionalization of a porous orthopedic implant with dexamethasone, a widely
      used anti-inflammatory drug, encapsulated within a biodegradable polymer for
      controlled release could help reduce or eliminate the inflammation response by
      the local tissue. In this research, we investigated the possibility of using
      supercritical carbon dioxide (CO2) for attaching dexamethasone-loaded PLGA
      (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous
      delivery of dexamethasone. Supercritical CO2 has been shown to be effective for
      attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached
      microspheres showed similar dexamethasone release profiles but different
      magnitude of burst release. Microspheres attached to the porous alloy samples
      using supercritical CO2 at 10 bar and 40  degrees C for 30 min showed a release
      profile similar to that of the nonattached microspheres. The microsphere
      morphology and the release profiles of microspheres attached to the glass plates
      and to the porous alloy samples suggest that dexamethasone burst release is
      enhanced by PLGA swelling at higher CO2 pressures and better dispersion of
      microspheres. This study shows that microspheres can be incorporated into porous
      solids using supercritical CO2, allowing for a wide variety of drug-biodegradable
      polymer formulations prepared using the proven emulsion/solvent evaporation
      method to be tested.

PMID- 20042431
TI  - Natural radionuclide content and radiological assessment of clay soils collected
      from different sites in Ekiti State, southwestern Nigeria.
AB  - Clay soil samples collected from different sites in Ekiti State, southwestern
      Nigeria were analysed for their natural radionuclide contents, using the gamma
      ray spectrometric method. The overall mean activity concentrations of (226)Ra,
      (232)Th and (40)K obtained in this study were, respectively, 33.6 +/- 5.3, 20.1
      +/- 3.3 and 207.2 +/- 113.0 Bq kg(-1). The radiological hazards incurred from the
      use of the clay soil as a component of building materials were estimated through
      various radiation hazard indices. The results indicate that the values obtained
      fall below the internationally accepted maximum limits and as such, the use of
      clay as a building material does not pose any significant radiation hazard to
      individuals in the study area.

PMID- 20042432
TI  - The principled control of false positives in neuroimaging.
AB  - An incredible amount of data is generated in the course of a functional
      neuroimaging experiment. The quantity of data gives us improved temporal and
      spatial resolution with which to evaluate our results. It also creates a
      staggering multiple testing problem. A number of methods have been created that
      address the multiple testing problem in neuroimaging in a principled fashion.
      These methods place limits on either the familywise error rate (FWER) or the
      false discovery rate (FDR) of the results. These principled approaches are well
      established in the literature and are known to properly limit the amount of false
      positives across the whole brain. However, a minority of papers are still
      published every month using methods that are improperly corrected for the number
      of tests conducted. These latter methods place limits on the voxelwise
      probability of a false positive and yield no information on the global rate of
      false positives in the results. In this commentary, we argue in favor of a
      principled approach to the multiple testing problem--one that places appropriate
      limits on the rate of false positives across the whole brain gives readers the
      information they need to properly evaluate the results.

PMID- 20042433
TI  - The increasing prevalence of listeriosis--what are we missing?

PMID- 20042434
TI  - Diet, lifestyle, and acute myeloid leukemia in the NIH-AARP cohort.
AB  - The relation between diet, lifestyle, and acute myeloid leukemia was assessed in
      a US cohort of 491,163 persons from the NIH-AARP Diet and Health Study (1995
      2003). A total of 338 incident cases of acute myeloid leukemia were ascertained.
      Multivariate Cox models were utilized to estimate hazard ratios and 95%
      confidence intervals. Compared with those for never smokers, hazard ratios were
      1.29 (95% confidence interval: 0.95, 1.75), 1.79 (95% confidence interval: 1.32,
      2.42), 2.42 (95% confidence interval: 1.63, 3.57), and 2.29 (85% confidence
      interval: 1.38, 3.79) for former smokers who smoked < or =1 or >1 pack/day and
      for current smokers who smoked < or =1 or >1 pack/day, respectively. Higher meat
      intake was associated with an increased risk of acute myeloid leukemia (hazard
      ratio = 1.45, 95% confidence interval: 1.02, 2.07 for the fifth vs. first
      quintile; P for trend = 0.06); however, there were no clear effects of meat
      cooking method or doneness level. Individuals who did not drink coffee appeared
      to have a higher risk of acute myeloid leukemia than those who drank various
      quantities of coffee. Neither fruit nor vegetable intake was associated with
      acute myeloid leukemia. This large prospective study identified smoking and meat
      intake as risk factors for acute myeloid leukemia.

PMID- 20042435
TI  - Maternal dietary glycemic intake and the risk of neural tube defects.
AB  - Both maternal diabetes and obesity have been associated with an increased risk of
      neural tube defects (NTD), possibly due to a sustained state of hyperglycemia
      and/or hyperinsulinemia. Data were collected in the Boston University Slone Birth
      Defects Study (a case-control study) from 1988 to 1998. The authors examined
      whether high dietary glycemic index (DGI) and high dietary glycemic load (DGL)
      increased the risk of NTDs in nondiabetic women. Mothers of NTD cases and
      nonmalformed controls were interviewed in person within 6 months after delivery
      about diet and other exposures. Odds ratios and 95% confidence intervals were
      estimated from logistic regression for high DGI (> or =60) and high DGL (> or
      =205), with cutpoints determined by cubic spline. Of 698 case mothers, 25% had
      high DGI and 4% had high DGL. Of 696 control mothers, 15% had high DGI and 2% had
      high DGL. After adjustment for sociodemographic factors and other dietary
      factors, the odds ratio for high DGI was 1.5 (95% confidence interval: 1.1, 2.0);
      for high DGL, it was 1.8 (95% confidence interval: 0.8, 4.0). Diets with
      proportionally high DGI or DGL may put the developing fetus at risk of an NTD,
      adding further evidence that hyperglycemia lies within the pathogenic pathway.

PMID- 20042437
TI  - Dairy intake and the risk of bladder cancer in the Netherlands Cohort Study on
      Diet and Cancer.
AB  - The authors examined the association between the intake of different dairy
      products and the risk of bladder cancer in 120,852 men and women aged 55-69 years
      participating in the Netherlands Cohort Study on Diet and Cancer. Dairy product
      intake was assessed in 1986 by using a 150-item food frequency questionnaire. The
      cohort was followed for 16.3 years, and 1,549 incident cases of bladder cancer
      were analyzed. Cox proportional hazards analysis was applied with a case-cohort
      approach by using the follow-up data of a random subcohort (n = 5,000).
      Multivariate hazard ratio estimates comparing the highest with the lowest
      quintile of total dairy intake were 1.01 (95% confidence interval (CI): 0.81,
      1.27; P(trend) = 0.68). A statistically significant association for fermented
      milk products was found only for the second quintile (median, 12 g/day) (hazard
      ratio = 0.71, 95% CI: 0.56, 0.91). Compared with nonconsumers, women with 25-75
      g/day of butter consumption had a hazard ratio of 1.61 (95% CI: 1.03, 2.50;
      P(trend) < 0.01). No association was found with cheese, calcium, lactose, or
      nonfermented dairy intake. These results provide weak evidence that bladder
      cancer risk is inversely associated with low intake of fermented dairy products
      and suggest a positive association with butter intake in women.

PMID- 20042436
TI  - The relevance of different methods of calculating the ankle-brachial index: the
      multi-ethnic study of atherosclerosis.
AB  - The authors aimed to determine differences in the prevalence of peripheral
      arterial disease (PAD) and its associations with cardiovascular disease (CVD)
      risk factors, using different methods of calculating the ankle-brachial index
      (ABI). Using measurements taken in the bilateral brachial, dorsalis pedis, and
      posterior tibial arteries, the authors calculated ABI in 3 ways: 1) with the
      lowest ankle pressure (dorsalis pedis artery or posterior tibial artery) ("ABI
      LO"), 2) with the highest ankle pressure ("ABI-HI"), and 3) with the mean of the
      ankle pressures ("ABI-MN"). For all 3 methods, the index ABI was the lower of the
      ABIs calculated from the left and right legs. PAD was defined as an ABI less than
      0.90. Among 6,590 subjects from a multiethnic cohort (baseline examination: 2000
      2002), in comparison with ABI-HI, the relative prevalence of PAD was 3.95 times
      higher in women and 2.74 times higher in men when ABI-LO was used. The relative
      magnitudes of the associations were largest between PAD and both subclinical
      atherosclerosis and CVD risk factors when ABI-HI was used, except when risk
      estimates for PAD were less than 1.0, where the largest relative magnitudes of
      association were found using ABI-LO. PAD prevalence and its associations with CVD
      risk factors and subclinical atherosclerosis measures depend on the ankle
      pressure used to compute the ABI.

PMID- 20042438
TI  - How does socioeconomic development affect risk of mortality? An age-period-cohort
      analysis from a recently transitioned population in China.
AB  - During the 20th century, the Hong Kong Chinese population experienced 2 abrupt
      but temporally distinct macroenvironmental changes: The transition from
      essentially preindustrial living conditions to a rapidly developing economy
      through mass migration in the late 1940s was followed by the emergence of an
      infant and childhood adiposity epidemic in the 1960s. The authors aimed to
      delineate the effects of these 2 aspects of economic development on mortality,
      thus providing a sentinel for other rapidly developing economies. Sex-specific
      Poisson models were used to estimate effects of age, calendar period, and birth
      cohort on Hong Kong adult mortality between 1976 and 2005. All-cause and cause
      specific mortality, including mortality from ischemic heart disease (IHD),
      cardiovascular disease excluding IHD, lung cancer, other cancers, and respiratory
      disease, were considered. Male mortality from IHD and female mortality from other
      cancers increased with birth into a more economically developed environment.
      Cardiovascular disease mortality increased with birth after the start of the
      infant and childhood adiposity epidemic, particularly for men. Macroenvironmental
      changes associated with economic development had sex-specific effects over the
      life course, probably originating in early life. The full population health
      consequences of these changes are unlikely to manifest until persons who have
      spent their early lives in such environments reach an age at which they become
      vulnerable to chronic diseases.

PMID- 20042439
TI  - Resistive-heating or forced-air warming for the prevention of redistribution
      hypothermia.
AB  - BACKGROUND: We evaluated the efficacy of resistive-heating or forced-air warming
      versus no prewarming, applied before induction of anesthesia for prevention of
      hypothermia. METHODS: Twenty-seven patients scheduled for laparoscopic colorectal
      surgery were randomized into 1 of 3 groups: no prewarming; 30 minutes of
      prewarming with a carbon fiber total body cover at 42 degrees C; or 30 minutes of
      preoperative forced-air warming at 42 degrees C. The forced-air warming cover
      excluded the shoulders, ankles, and feet. The prewarming period was exactly 30
      minutes. At the 31st minute, a total IV anesthesia technique was initiated, and
      all patients were actively warmed with a lithotomy blanket. Tympanic and distal
      esophageal temperatures were measured. Categorical data were analyzed using
      chi(2) test, and continuous data were analyzed with analysis of variance. P <0.05
      was considered statistically significant. RESULTS: The mean esophageal
      temperatures differed significantly between the control and the carbon fiber
      group from 40 to 90 minutes of anesthesia. After 50 minutes of anesthesia, the
      mean esophageal temperatures in the control, carbon fiber, and forced-air groups
      were 35.9 degrees C +/- 0.3 degrees C, 36.5 degrees C +/- 0.4 degrees C, and 36.2
      degrees C +/- 0.3 degrees C, respectively. No statistically significant
      difference was found between the forced-air and control groups. After 30 minutes
      of prewarming with resistive heating, patients had an esophageal temperature that
      was significantly higher than the control group. CONCLUSIONS: Prewarming should
      be considered part of the anesthetic management when patients are at risk for
      postoperative hypothermia.

PMID- 20042440
TI  - Nocebo-induced hyperalgesia during local anesthetic injection.
AB  - Common practice during local anesthetic injection is to warn the patient using
      words such as: "You will feel a big bee sting; this is the worst part." Our
      hypothesis was that using gentler words for administration of the local
      anesthetic improves pain perception and patient comfort. One hundred forty
      healthy women at term gestation requesting neuraxial analgesia were randomized to
      either a "placebo" ("We are going to give you a local anesthetic that will numb
      the area and you will be comfortable during the procedure") or "nocebo" ("You are
      going to feel a big bee sting; this is the worst part of the procedure") group.
      Pain was assessed immediately after the local anesthetic skin injection using
      verbal analog scale scores of 0 to 10. Median verbal analog scale pain scores
      were lower when reassuring words were used compared with the harsher nocebo words
      (3 [2-4] vs 5 [3-6]; P < 0.001). Our data suggest that using gentler, more
      reassuring words improves the subjective experience during invasive procedures.

PMID- 20042441
TI  - The effects of the phosphodiesterase inhibitor olprinone on global cerebral
      ischemia.
AB  - BACKGROUND: The phosphodiesterase III inhibitor olprinone has been confirmed to
      improve myocardial function and increase cerebral blood flow; therefore, if
      olprinone exerts direct neuroprotective effects against global cerebral ischemia
      to the same degree as cilostazol, olprinone could be useful for cerebral
      resuscitation after cardiac arrest. We examined whether olprinone directly
      protected neuronal cells from global cerebral ischemia both in vivo and in vitro.
      METHODS: In a rat model of 10-minute global cerebral ischemia induced by 4-vessel
      occlusion, 0.3, 3, or 30 microg x kg(-1) x min(-1) olprinone or saline was
      infused for a periischemic period of 40 minutes (n = 6 for each group).
      Hippocampal CA1 neuronal cells were then counted 3 days after reperfusion, and
      the phosphorylation of cyclic adenosine 3'5'-monophosphate response element
      binding protein was examined using Western blotting analyses of specimens
      obtained 15 minutes after reperfusion. In vitro, cultured cerebral neurons were
      exposed to 4 hours of hypoxia and glucose deprivation and then 24 hours of
      recovery in the absence or presence of olprinone (10(-11)-10(-5) mol x L(-1)).
      Cell viability was measured using the Cell Counting Kit-8 (Dojindo Molecular
      Technologies, Gaithersburg, MD). RESULTS: In the rat model of global ischemia,
      the number of surviving CA1 neurons counted under a microscopic field in the 30
      microg x kg(-1) x min(-1) olprinone-treated group (49.9 +/- 9.2) was
      significantly higher than that in the saline infusion control group (7.2 +/-
      3.4), and olprinone treatment increased the phosphorylation of cyclic adenosine
      3'5'-monophosphate response element-binding protein. The survival fraction of the
      neuronal cells cultured in the presence of olprinone was also significantly
      higher than that of cells cultured in the absence of olprinone in a dose
      dependent manner. CONCLUSIONS: Our study successfully demonstrated, for the first
      time, that olprinone had a protective effect on neuronal cells in vitro and in
      vivo, especially against global cerebral ischemia. These results suggest that
      olprinone might be useful for the treatment of patients experiencing global
      cerebral ischemia.

PMID- 20042442
TI  - Resistive-polymer versus forced-air warming: comparable efficacy in orthopedic
      patients.
AB  - BACKGROUND: Several adverse consequences are caused by mild perioperative
      hypothermia. Maintaining normothermia with patient warming systems, today mostly
      with forced air (FA), has thus become a standard procedure during anesthesia.
      Recently, a polymer-based resistive patient warming system was developed. We
      compared the efficacy of a widely distributed FA system with the resistive
      polymer (RP) system in a prospective, randomized clinical study. METHODS: Eighty
      patients scheduled for orthopedic surgery were randomized to either FA warming
      (Bair Hugger warming blanket #522 and blower #750, Arizant, Eden Prairie, MN) or
      RP warming (Hot Dog Multi-Position Blanket and Hot Dog controller, Augustine
      Biomedical, Eden Prairie, MN). Core temperature, skin temperature (head, upper
      and lower arm, chest, abdomen, back, thigh, and calf), and room temperature
      (general and near the patient) were recorded continuously. RESULTS: After an
      initial decrease, core temperatures increased in both groups at comparable rates
      (FA: 0.33 degrees C/h +/- 0.34 degrees C/h; RP: 0.29 degrees C/h +/- 0.35 degrees
      C/h; P = 0.6). There was also no difference in the course of mean skin and mean
      body (core) temperature. FA warming increased the environment close to the
      patient (the workplace of anesthesiologists and surgeons) more than RP warming
      (24.4 degrees C +/- 5.2 degrees C for FA vs 22.6 degrees C +/- 1.9 degrees C for
      RP at 30 minutes; P(AUC) <0.01). CONCLUSION: RP warming performed as efficiently
      as FA warming in patients undergoing orthopedic surgery.

PMID- 20042443
TI  - When blood is not an option: factors affecting survival after the use of a
      hemoglobin-based oxygen carrier in 54 patients with life-threatening anemia.
AB  - BACKGROUND: In consenting Jehovah's Witness patients and others for whom blood is
      contraindicated or not available, hemoglobin-based oxygen carrier (HBOC)-201 may
      enable survival in acutely anemic patients while underlying conditions are
      treated. METHODS: Survival factors were identified in a multicenter, unblinded
      series of severely anemic "compassionate use" patients receiving available
      standard treatment plus consultant-supported HBOC-201 administration by novice
      users. Predictors of outcome were sought and compared between survivors and
      nonsurvivors. A compound variable, hemoglobin-duration deficit product was used
      to describe the interactive clinical effects of severity and duration of anemia.
      Mortality,correlations between patient characteristics, and survival to hospital
      discharge were determined from patient records. RESULTS: Fifty-four patients
      (median age 50 years) with life-threatening anemia (median hemoglobin
      concentration at time of request = 4 g/dL) received 60 to 300 g HBOC-201.Twenty
      three patients (41.8%) were discharged. Intraoperative blood loss (45%),
      malignancy(18%), and acute hemolysis (13%) were the prevailing reasons for
      anemia. Time from onset of anemia (< or = 8 g/dL) to HBOC-201 infusion was
      shorter for survivors than nonsurvivors (3.2 vs 4.4 days, P = 0.027). Mean
      hemoglobin levels before HBOC-201 infusion in survivors and nonsurvivors were 4.5
      and 3.8 g/dL, respectively (P = 0.120). No serious adverse event was attributed
      to HBOC-201. The hemoglobin-duration deficit product separated survivors from
      nonsurvivors. Cancer and renal disease were associated with nonsurvival.
      CONCLUSION: Earlier, compared with later, administration by inexperienced users
      of HBOC-201 to patients with anemia was associated with improved chances of
      survival of acutely bleeding and hemolyzing patients. Survival was more likely if
      the duration and magnitude of low hemoglobin was minimized before treatment with
      HBOC-201.

PMID- 20042444
TI  - A point-of-care assessment of the effects of desmopressin on impaired platelet
      function using multiple electrode whole-blood aggregometry in patients after
      cardiac surgery.
AB  - BACKGROUND: Blood loss after cardiac surgery can be caused by acquired platelet
      dysfunction after cardiopulmonary bypass. Monitoring of platelet function is
      clinically important for the identification of patients experiencing such
      platelet dysfunction. 1-Deamino-8-D-arginine vasopressin (desmopressin acetate,
      DDAVP) has been shown to augment platelet function and to reduce blood loss in
      patients with platelet dysfunction. In this study, we examined the feasibility of
      whole blood multiple electrode aggregometry (MEA) for the detection of
      cardiopulmonary bypass-induced platelet dysfunction and investigated its ability
      to monitor DDAVP treatment. METHODS: Fifty-eight consecutive patients with blood
      loss exceeding 150 mL/h in the first 2 consecutive hours after cardiac surgery
      were screened for suspected isolated platelet dysfunction. Twenty-two patients
      had suspected isolated platelet dysfunction and were enrolled in the study.
      Platelet dysfunction was assumed if conventional coagulation analyses (platelet
      count, activated partial thromboplastin time, international normalized ratio, and
      fibrinogen) did not show abnormal values as defined for transfusion of allogenic
      blood products, and no surgical cause of bleeding was suspected. Eleven patients
      received 0.3 microg/kg DDAVP, and 11 patients received no therapy in a
      nonrandomized manner. MEA was performed after stimulation with thrombin receptor
      activating peptide (TRAPtest, 32 microM), adenosine diphosphate (ADPtest, 6.4
      microM), and arachidonic acid (ASPItest, 0.5 mM) before and 2 hours after
      intervention. Conventional laboratory variables were recorded. The Mann-Whitney
      test was used to detect differences between the groups, and the Wilcoxon test was
      used to detect differences before and after intervention. RESULTS: All enrolled
      patients showed platelet dysfunction that manifested as impaired platelet
      aggregation in MEA before intervention. After the intervention, platelet function
      improved in the DDAVP group (49 U [30/72 U], median [25th/75th percentile]
      postintervention vs 15 U [8/21 U] preintervention for the ASPItest [P < 0.001];
      35 U [24/54 U] vs 14 U [7/28 U] for the ADPtest [P = 0.002]; and 85 U [66/115 U]
      vs 64 U [26/88 U] for the TRAPtest [P = 0.007]). In contrast, MEA remained
      unchanged in the control group (22 U [10/50 U] postintervention vs 33 U [14/57 U]
      preintervention for the ASPItest [P = 0.175]; 17 U [12/20 U] vs 14 U [10/28 U]
      for the ADPtest [P = 0.147]; and 65 U [41/89 U] vs 57 U [30/91 U] for the
      TRAPtest [P = 0.123]). CONCLUSIONS: Impaired platelet function after cardiac
      surgery can be assessed at the bedside using MEA. The effect of DDAVP on impaired
      platelet function can also be detected as significant improvement in platelet
      aggregation to all activators. This device might be helpful for the
      identification of patients who may benefit from DDAVP therapy.

PMID- 20042445
TI  - The role of echocardiography in the management of an embolized atrial septal
      Helex occluder.

PMID- 20042447
TI  - Ebstein anomaly of the tricuspid valve, atrial septal defect, and severe right
      ventricular dysfunction in an adult: transesophageal echocardiographic images.

PMID- 20042446
TI  - Local administration of morphine for analgesia after autogenous anterior or
      posterior iliac crest bone graft harvest for spinal fusion: a prospective,
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Harvesting of iliac crest graft for spinal fusions is associated with
      a number of patients reporting residual or chronic pain at the harvest site.
      Various interventions, including morphine infiltration, have been proposed to
      minimize the associated pain. METHODS: We performed a prospective, double-blind,
      randomized, placebo-controlled study comparing intraoperative infiltration of 5
      mg morphine (treatment) versus saline (placebo) into the iliac crest harvest site
      for patients undergoing elective spinal surgery. Patients with myelopathy,
      excessive perioperative opioid use (60 mg equivalent morphine/d or more), or
      multilevel (>3 levels) spinal surgery were excluded. Postoperative administration
      of morphine (recovery room and patient-controlled analgesia) was standardized.
      Numerical pain scores specific for the iliac crest site were determined in the
      immediate postoperative period and at 3, 6, and 12 months. RESULTS: Of the 54
      patients randomized, 47 (87%) were available for review with a minimum of 1-year
      follow-up. The groups were similar in baseline age, gender, and comorbidities.
      There was no significant difference between groups in total use of postoperative
      morphine during the first 24 hours (P = 0.48). Repeated measures analysis of
      variance demonstrated no interacting effect of group over time for hip pain at
      rest (P = 0.94), hip pain while moving (P = 0.90), spine pain at rest (P = 0.99),
      or spine pain while moving (P = 0.83). The proportion of patients reporting iliac
      crest pain at 1-year follow-up was the same between groups (P = 0.95).
      CONCLUSIONS: This study has demonstrated that there are no additional benefits
      for the use of intraoperative infiltration of morphine into the iliac crest
      harvest site during spinal fusions.

PMID- 20042448
TI  - Overcoming clinical inertia to achieve blood pressure goals: the role of fixed
      dose combination therapy.
AB  - The treatment of hypertension should cause blood pressure (BP) changes that
      reduce the long-term risks of cardiovascular morbidity and mortality. There are
      considerable clinical benefits to be gained by promptly treating patients to
      recognized BP goals, particularly for those at high risk. This may be achieved by
      the use of combination therapy as first-line treatment. However, despite widely
      acknowledged therapeutic guidelines, there are significant gaps between current
      treatment recommendations and their implementation in clinical practice. One
      important explanation for inadequate treatment and subsequent poor BP control is
      clinical inertia. Undertreatment and clinical inertia may sometimes be mistaken
      for treatment-resistant hypertension, as is often the case in specific patient
      populations whose disease is often considered a challenge to treat because of a
      greater risk of cardiovascular complications (e.g. Blacks, obese patients, and
      those with diabetes). The availability of fixed-dose drug combinations may
      address some of the common misconceptions thought to promote clinical inertia.
      Few studies have specifically focused on subpopulations with difficult-to-treat
      hypertension that is uncontrolled on monotherapies. One example is an ongoing 20
      week, multicenter, prospective, blinded endpoint, dose-titration, treat-to-goal
      study evaluating the efficacy and safety of initial fixed-dose combination
      therapy with amlodipine/olmesartan medoxomil, and further up-titration with
      hydrochlorothiazide, in patients with hypertension who are uncontrolled on
      antihypertensive monotherapy. This study may demonstrate the benefits of treating
      patients with hypertension to goal using initial fixed-dose combination therapy,
      even in patients considered to be at a higher risk of cardiovascular
      complications.

PMID- 20042449
TI  - Stem cell-mediated neovascularization in heart repair.
AB  - Accumulating clinical and experimental evidence indicates that stem cells from
      various sources are promising in the treatment of cardiac dysfunction. They may
      be incorporated into neovascular foci and thus contribute to postnatal
      physiological and pathological vasculogenesis and/or produce a variety of growth
      factors for angiogenesis and cytokines that home other stem cells from other
      organs for cardiac regeneration. This review focuses on the neovascularization of
      stem cells from different sources in cardiac repair, with emphasis on adult stem
      cells.

PMID- 20042450
TI  - Individualizing hypertension treatment with impedance cardiography: a meta
      analysis of published trials.
AB  - OBJECTIVE: Hypertension affects 73 million Americans and costs the US healthcare
      system over $73 billion annually. Despite increasing awareness of the
      consequences of uncontrolled hypertension, numerous antihypertensive
      pharmacologic clinical studies and consistent updates to hypertension guidelines,
      control rates are suboptimal and have not met national goals. Among treated
      hypertensives, only 45% of women and 51% of men have reached blood pressure (BP)
      levels below 140/90 mmHg. Individualization of antihypertensive regimens with
      hemodynamic information from impedance cardiography (ICG) has been advocated to
      further improve hypertension control rates. We therefore undertook a quantitative
      analysis of the trials evaluating the role of ICG as an adjunct to therapeutic
      decision-making in the treatment of hypertension and the attainment of BP
      control. METHODS: Five studies comprising a total population of 759 patients met
      the inclusion criteria. Two randomized controlled trials (RCTs) involving a total
      of 268 patients and three single-arm prospective trials with 491 patients were
      evaluated using ICG data to guide therapeutic decision-making in the treatment of
      hypertensive patients. RESULTS: Significant benefit was found in both RCTs for
      ICG-guided BP treatment. The combined odds ratio for the two trials was 2.41 (95%
      CI = 1.44-4.05, p = 0.0008), in favor of ICG treatment, meaning that it was more
      than twice as likely to achieve BP success when using ICG than if ICG was not
      used. Success attainment of goal BP of <140/90 mmHg was 67% in the ICG-guided
      arms of the combined randomized trials. Overall success in the single-arm
      prospective trials of ICG-guided BP treatment was a similar 68%. CONCLUSION: The
      results of this meta-analysis confirm the value of using ICG-derived hemodynamic
      data as an adjunct to therapeutic decision-making in the treatment of
      hypertension. The data reviewed here demonstrate that ICG-based approaches are in
      keeping with previously advocated strategies incorporating patient-individualized
      drug regimens, evidence-based medicine, and practical, easy to apply, cost
      effective principles to further improve hypertension control rates.

PMID- 20042451
TI  - Vibration response imaging (VRI) in lung transplant recipients.
AB  - BACKGROUND: In the first 6 months following lung transplantation, the most
      frequently occurring complications are infection, acute rejection and anastomotic
      dysfunction. The utility of vibration response imaging (VRI) lung images in
      assisting with the detection of these complications was evaluated. OBJECTIVES:
      The study aimed to evaluate if VRI is a good, non-invasive method of detecting
      clinical problems in lung transplant (LTx) recipients during early follow-up.
      METHODS: Between 06/2006 and 03/2007 all LTx patients who received transplants
      during the preceding 6 months at the Hannover Medical School received baseline
      VRI at enrollment with subsequent reassessment in combination with standard
      follow-up at 1, 3 and 6 months thereafter. The resulting images were analysed by
      two blinded reviewers. RESULTS: Fifty-five lung transplant recipients were
      enrolled in the study, with 49 patients successfully completing follow-up. Device
      operability and patient participation occurred without significant problems. High
      numbers of abnormal scans were detected. According to the clinical diagnosis, 29
      patients (59.2 %) were stable at all four visits. Twenty clinical problems
      occurred (e.g., infections, rejections, obstructions, unknown deterioration).
      Agreement with clinical interpretation of rejections and infections was poor.
      Central airway obstruction (CAO) was detected in 80% by both reviewers. Accuracy
      in detecting obstructions was 89%; positive predicted value and negative
      predicted value were 80% and 90%, respectively. CONCLUSION: The VRI system is a
      non-invasive easy-to-use method with technical success and good image quality.
      The high number of abnormal scans makes interpretation following LTx difficult.
      VRI was unable to detect deterioration in graft function with the exception of
      ventilation disorders like central airway complications.

PMID- 20042452
TI  - Seawater gel in allergic rhinitis: entrapment effect and mucociliary clearance
      compared with saline.
AB  - OBJECTIVE: We performed a prospective study to investigate the the efficacy of
      seawater gel in reducing symptoms in patients with mild allergic rhinitis. We
      also aimed to investigate the impact of nasal irrigation on mucociliary clearance
      with seawater gel compared with saline in this patient group. METHODS: The study
      was performed in 100 consecutive adult individuals with a history of allergic
      rhinitis that was not controlled by anti-allergic drugs. Patients were assigned
      to receive seawater gel nasal spray for 10 days. The efficacy of treatment was
      assessed by means of total nasal symptom score and clinical findings. RESULTS: A
      statistically significant difference was found between scores of 'nasal
      discharge, nasal obstruction, sneezing, nasal itching'before and after treatment
      (p < 0.001). Clinical findings evaluation revealed a statistically significant
      decrease in lower turbinate colour rating and turbinate congestion at the end of
      treatment (p< 0.001). Saccharin transit time decreased from baseline in the
      seawater trials by 12% compared with a 4% decrease for saline. The difference
      between the percent changes was statistically significant (t = 2.177; p < 0.05).
      CONCLUSIONS: The present study provides evidence that a four times daily regimen
      of seawater gel can be an adjunctive therapy in the patient with allergic
      rhinitis.

PMID- 20042453
TI  - Short commentary on 'a consensus protocol for the standardization of
      cerebrospinal fluid collection and biobanking'.

PMID- 20042454
TI  - Identification of TOSO/FAIM3 as an Fc receptor for IgM.
AB  - Fc receptors specifically bind to the Fc region of Igs to mediate the unique
      functions to each class of Igs. To identify a novel Fc receptor for IgM, we
      searched expressed sequence tag database for molecules containing Ig domains with
      homology to those of known Fc receptors for IgM, Fcalpha/muR and polymeric Ig
      receptor. As a result, we identified TOSO/Fas apoptotic inhibitory molecule 3
      (FAIM3) as a possible Fc receptor for IgM. HeLa cells transfected with a
      TOSO/FAIM3-expression vector bound to IgM but not IgG and were able to
      internalize IgM-conjugated beads but not IgG-conjugated beads, suggesting that
      TOSO/FAIM3 is indeed a receptor for IgM (FcmuR). FcmuR protein was expressed
      predominantly on B-lineage cells; expression of the Fcmr transcripts was observed
      from the pre-B-cell stage and maintained thereafter during B-cell development.
      These results identify TOSO/FAIM3 as a receptor for IgM and suggest that FcmuR
      may serve as an uptake receptor for IgM-opsonized antigens by B cells.

PMID- 20042455
TI  - IL-6 positively regulates Foxp3+CD8+ T cells in vivo.
AB  - Although recent studies have identified regulatory roles for Foxp3(+)CD8(+) T
      cells, the mechanisms that induce their development and underlie their functions
      in vivo have not been elucidated. Here, we show that IL-6 positively regulates
      the Foxp3(+)CD8(+) T-cell development and function. The Foxp3(+)CD8(+) T cells
      that differentiated in vitro in the presence of IL-6 suppressed autoimmune
      colitis and arthritis in vivo. Moreover, Foxp3(+)CD8(+) T cells that developed in
      vivo in the presence of enhanced IL-6 signaling suppressed the development of a
      spontaneous T(h)17 cell-mediated autoimmune arthritis. Thus, we concluded that
      Foxp3(+)CD8(+) T cells develop in response to IL-6 and regulate chronic
      inflammation in T(h)17 cell-mediated F759 autoimmune arthritis. These results
      suggested that Foxp3(+)CD8(+) T cells may develop in response to IL-6 under
      certain inflammatory conditions in vivo and may regulate some other chronic
      inflammation diseases.

PMID- 20042456
TI  - Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y)
      (Akita) mice.
AB  - Previous studies have shown that Akita mice bearing the Ins2(+/C96Y) mutation
      have significant advantages as a type I diabetes platform for developing models
      of diabetic nephropathy (DN; Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW,
      Coffman TM. Am J Physiol Renal Physiol 290: F214-F222, 2006). In view of the
      critical role for genetic factors in determining susceptibility to DN in humans,
      we investigated the role of genetic background on kidney injury in Akita mice. To
      generate a series of inbred Akita mouse lines, we back-crossed the Ins2(C96Y)
      mutation more than six generations onto the 129/SvEv and DBA/2 backgrounds and
      compared the extent of hyperglycemia and renal disease with the standard C57BL/6
      Ins2(+/C96Y) line. Male mice from all three Akita strains developed marked and
      equivalent hyperglycemia. However, there were significant differences in the
      level of albuminuria among the lines with a hierarchy of DBA/2 > 129/SvEv >
      C57BL/6. Renal and glomerular hypertrophy was seen in all of the lines, but
      significant increases in mesangial matrix compared with baseline nondiabetic
      controls were observed only in the 129 and C57BL/6 backgrounds. In F1(DBA/2 x
      C57BL/6)-Ins2(+/C96Y) mice, the extent of albuminuria was similar to the parental
      DBA/2-Ins2(+/C96Y) line; they also developed marked hyperfiltration. These
      studies identify strong effects of genetic background to modify the renal
      phenotype associated with the Ins2(C96Y) mutation. Identification of these
      naturally occurring strain differences should prove useful for nephropathy
      modeling and may be exploited to allow identification of novel susceptibility
      alleles for albuminuria in diabetes.

PMID- 20042457
TI  - Vasopressin regulates the renal Na+-Cl- cotransporter.

PMID- 20042458
TI  - Angiotensin type 2 receptor actions contribute to angiotensin type 1 receptor
      blocker effects on kidney fibrosis.
AB  - Angiotensin type 1 (AT1) receptor blocker (ARB) ameliorates progression of
      chronic kidney disease. Whether this protection is due solely to blockade of AT1,
      or whether diversion of angiotensin II from the AT1 to the available AT2
      receptor, thus potentially enhancing AT2 receptor effects, is not known. We
      therefore investigated the role of AT2 receptor in ARB-induced treatment effects
      in chronic kidney disease. Adult rats underwent 5/6 nephrectomy.
      Glomerulosclerosis was assessed by renal biopsy 8 wk later, and rats were divided
      into four groups with equivalent glomerulosclerosis: no further treatment, ARB,
      AT2 receptor antagonist, or combination. By week 12 after nephrectomy, systolic
      blood pressure was decreased in all treatment groups, but proteinuria was
      decreased only with ARB. Glomerulosclerosis increased significantly in AT2
      receptor antagonist vs. ARB. Kidney cortical collagen content was decreased in
      ARB, but increased in untreated 5/6 nephrectomy, AT2 receptor antagonist, and
      combined groups. Glomerular cell proliferation increased in both untreated 5/6
      nephrectomy and AT2 receptor antagonist vs. ARB, and phospho-Erk2 was increased
      by AT2 receptor antagonist. Plasminogen activator inhibitor-1 mRNA and protein
      were increased at 12 wk by AT2 receptor antagonist in contrast to decrease with
      ARB. Podocyte injury is a key component of glomerulosclerosis. We therefore
      assessed effects of AT1 vs. AT2 blockade on podocytes and interaction with
      plasminogen activator inhibitor-1. Cultured wild-type podocytes, but not
      plasminogen activator inhibitor-1 knockout, responded to angiotensin II with
      increased collagen, an effect that was completely blocked by ARB with lesser
      effect of AT2 receptor antagonist. We conclude that the benefical effects on
      glomerular injury achieved with ARB are contributed to not only by blockade of
      the AT1 receptor, but also by increasing angiotensin effects transduced through
      the AT2 receptor.

PMID- 20042459
TI  - Role of 5-HT1A receptors in control of lower urinary tract function in
      anesthetized rats.
AB  - The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary
      tract function was examined in urethane-anesthetized female Sprague-Dawley rats.
      Bladder pressure and the external urethral sphincter electromyogram (EUS EMG)
      activity were recorded during continuous-infusion transvesical cystometrograms
      (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which
      prevented voiding and allowed recording of isovolumetric bladder contractions. 8
      Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1A receptor agonist,
      decreased volume threshold (VT) for initiating voiding and increased contraction
      amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT
      prolonged EUS bursting as well as the intrabursting silent periods (SP) during
      voiding. N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]-N-(2
      pyridinyl)cyclohexanecarboxamine trihydrochloride (WAY-100635), a 5-HT1A
      antagonist, increased VT, increased residual volume, markedly decreased voiding
      efficiency, decreased the amplitude of micturition contractions recorded under
      isovolumetric conditions, and decreased the SP of EUS bursting. These results
      indicate that activation of 5-HT1A receptors by endogenous 5-HT lowers the
      threshold for initiating reflex voiding and promotes voiding function by
      enhancing the duration of EUS relaxation, which should reduce urethral outlet
      resistance.

PMID- 20042460
TI  - Hyperfiltration and inner stripe hypertrophy may explain findings by Gamble and
      coworkers.
AB  - Simulations conducted in a mathematical model were used to exemplify the
      hypothesis that elevated solute concentrations and tubular flows at the boundary
      of the renal outer and inner medullas of rats may contribute to increased urine
      osmolalities and urine flow rates. Such elevated quantities at that boundary may
      arise from hyperfiltration and from inner stripe hypertrophy, which are
      correlated with increased concentrating activity (Bankir L, Kriz W. Kidney Int.
      47: 7-24, 1995). The simulations used the region-based model for the rat inner
      medulla that was presented in the companion study (Layton AT, Pannabecker TL,
      Dantzler WH, Layton HE. Am J Physiol Renal Physiol 298: F000-F000, 2010). The
      simulations were suggested by experiments which were conducted in rat by Gamble
      et al. (Gamble JL, McKhann CF, Butler AM, Tuthill E. Am J Physiol 109: 139-154,
      1934) in which the ratio of NaCl to urea in the diet was systematically varied in
      eight successive 5-day intervals. The simulations predict that changes in
      boundary conditions at the boundary of the outer and inner medulla, accompanied
      by plausible modifications in transport properties of the collecting duct system,
      can significantly increase urine osmolality and flow rate. This hyperfiltration
      hypertrophy hypothesis may explain the finding by Gamble et al. that the maximum
      urine osmolality attained from supplemental feeding of urea and NaCl in the eight
      intervals depends on NaCl being the initial predominant solute and on urea being
      the final predominant solute, because urea in sufficient quantity appears to
      stimulate concentrating activity. More generally, the hypothesis suggests that
      high osmolalities and urine flow rates may depend, in large part, on adaptive
      modifications of cortical hemodynamics and on outer medullary structure and not
      entirely on an extraordinary concentrating capability that is intrinsic to the
      inner medulla.

PMID- 20042461
TI  - IL-17A and IL-17F stimulate chemokines via MAPK pathways (ERK1/2 and p38 but not
      JNK) in mouse cultured mesangial cells: synergy with TNF-alpha and IL-1beta.
AB  - We investigated the role of IL-17 family members IL-17A and IL-17F in the
      induction of chemokines in mouse cultured mesangial cells (SV40 MES 13 cells). We
      evaluated the expression of the chemokines monocyte chemoattractant protein-1
      (MCP-1) and macrophage inflammatory protein-2 (MIP-2) by ELISA and real-time RT
      PCR (Q-PCR). Activation of MAPK was assessed by immunoblotting. IL-17RA and IL
      17RC were inhibited by small interfering RNA (siRNA). We found that IL-17A or IL
      17F stimulation of mesangial cells led to both a dose- and time-dependent
      increase in MCP-1 and MIP-2 release. This effect was dependent on mRNA
      transcription and protein translation. Both also enhanced TNF-alpha- and IL-1beta
      mediated MCP-1 and MIP-2 release in the cells. Additionally, we observed that IL
      17A and IL-17F induced MAPK (p38 MAPK, ERK1/2, and JNK) activation and that
      pharmacological inhibitors of p38 MAPK (SB203580) and ERK1/2 (U0126), but not JNK
      (SP600125), blocked the IL-17A/IL-17F-mediated MCP-1 and MIP-2 release. Mesangial
      cells expressed IL-17RA and IL-17RC, and the IL-17A-mediated MCP-1 and MIP-2
      release was significantly blocked by soluble IL-17RA. Furthermore, inhibition of
      either IL-17RA or IL-17RC expression via siRNA led to significant reduction of IL
      17A/IL-17F-stimulated chemokine production. We conclude that IL-17A and IL-17F
      induce the production of chemokines MCP-1 and MIP-2 via MAPK pathways (p38 MAPK
      and ERK1/2), as well as mRNA transcription and protein translation and have
      synergistic effects with TNF-alpha and IL-1beta in cultured mesangial cells.

PMID- 20042462
TI  - Functional SNP of ARHGEF10 confers risk of atherothrombotic stroke.
AB  - Although stroke is a common cause of death and a major cause of disability all
      over the world, genetic components of common forms of ischemic stroke are largely
      unknown. To identify susceptibility genes of atherothrombotic stroke, we
      performed a large case-control association study and a replication study in a
      total of 2775 cases with atherothrombotic stroke and 2839 controls. Through the
      analysis in 860 cases and 860 age- and sex-matched controls, we found that a
      single-nucleotide polymorphism (SNP), rs2280887, in the ARHGEF10 gene was
      significantly associated with atherothrombotic stroke even after the adjustment
      of multiple testing by a permutation test [unadjusted P = 1.2 x 10(-6), odds
      ratio = 1.80, 95% confidence interval (CI) = 1.42-2.28]. This association was
      replicated in independent 1915 cases and 1979 controls. Subsequent fine mapping
      found another three SNPs which showed similar association due to strong linkage
      disequilibrium to rs2280887 (r(2) > 0.95). In the functional analyses of these
      four highly associated SNPs, using luciferase assay and electrophoretic mobility
      shift assay we found that rs4376531 affected ARHGEF10 transcriptional activity
      due to the different Sp1-binding affinity. In small GTPase activity assay, we
      found that a gene product of ARHGEF10 specifically activated RhoA. A population
      based cohort study revealed the subjects with rs4376531 CC or CG to increase the
      incidence of ischemic stroke (P = 0.033, hazard ratio = 1.79, 95% CI = 1.05
      3.04). Our data suggest that the functional SNP of ARHGEF10 confers the
      susceptibility to atherothrombotic stroke.

PMID- 20042463
TI  - Sym1, the yeast ortholog of the MPV17 human disease protein, is a stress-induced
      bioenergetic and morphogenetic mitochondrial modulator.
AB  - A peculiar form of hepatocerebral mtDNA depletion syndrome is caused by mutations
      in the MPV17 gene, which encodes a small hydrophobic protein of unknown function
      located in the mitochondrial inner membrane. In order to define the molecular
      basis of MPV17 variants associated with the human disorder, we have previously
      taken advantage of S. cerevisiae as a model system thanks to the presence of an
      MPV17 ortholog gene, SYM1. We demonstrate here that the SYM1 gene product is
      essential to maintain OXPHOS, glycogen storage, mitochondrial morphology and
      mtDNA stability in stressing conditions such as high temperature and ethanol
      dependent growth. To gain insight into the molecular basis of the Sym1-less
      phenotype, we identified and characterized multicopy suppressor genes and
      metabolic suppressor compounds. Our results suggest that (i) metabolic impairment
      and mtDNA instability occur independently from each other as a consequence of
      SYM1 ablation; (ii) ablation of Sym1 causes depletion of glycogen storage,
      possibly due to defective anaplerotic flux of tricarboxylic acid (TCA) cycle
      intermediates to the cytosol; (iii) flattening of mitochondrial cristae in Sym1
      defective organelles suggests a role for Sym1 in the structural preservation of
      the inner mitochondrial membrane, which could in turn control mtDNA maintenance
      and stability.

PMID- 20042465
TI  - Quantification and identification of culturable airborne bacteria from duck
      houses.
AB  - Employees at agricultural working places are often exposed to complex
      bioaerosols. Investigations of bioaerosols in duck houses revealed concentrations
      of cultivable bacteria between 0.4 and 3 x 10(5) colony forming units (CFU) m(-3)
      on tryptone soy agar, 0.3 and 2 x 10(5) CFU m(-3) on actinomycetes isolation
      agar, and 0.8 and 5 x 10(3) CFU m(-3) on Middlebrook agar, respectively, when
      incubated at 25 degrees C. At an incubation temperature of 37 degrees C, 0.6-3 x
      10(2) CFU m(-3) were counted on MacConkey agar and 0.3-2 x 10(3) CFU m(-3) on
      Middlebrook agar, and the concentrations of bacteria on glycerol-arginine agar
      and oatmeal agar incubated at 50 degrees C varied between 0.1 and 2 x 10(3) and 1
      and 7 x 10(3) CFU m(-3), respectively. In addition, high concentrations of cells
      were observed by fluorescence microscope quantification of cell counts after 4',6
      diamidino-2-phenylindol staining with 3-8 x 10(7) cells m(-3). A total of 213
      colonies with different morphological appearance were selected and the isolated
      pure cultures were identified at the genus level using the 16S rRNA gene sequence
      analyses. In summary, 19 different genera of Actinobacteria, four genera of the
      Firmicutes, one genus of the Bacteroidetes, and five genera of the Proteobacteria
      were identified. Several isolates represent new phylogenetic lineages. Based on
      16S rRNA gene analyses, some isolates were most closely related to
      Cellulosimicrobium funkei, Corynebacterium falsenii, Corynebacterium xerosis,
      Mycobacterium arupense, and Staphylococcus epidermidis, which have been grouped
      into Risk group 2 of biological agents and may cause negative pulmonary health
      effects. These bacterial species were present in high concentrations up to 10(4)
      CFU m(-3). For this reason, we recommend an adequate personal breathing
      protection at these working places.

PMID- 20042464
TI  - The Leber congenital amaurosis protein, AIPL1, is needed for the viability and
      functioning of cone photoreceptor cells.
AB  - Leber congenital amaurosis (LCA) caused by mutations in Aryl hydrocarbon receptor
      interacting protein like-1 (Aipl1) is a severe form of childhood blindness. At 4
      weeks of age, a mouse model of LCA lacking AIPL1 exhibits complete degeneration
      of both rod and cone photoreceptors. Rod cell death occurs due to rapid
      destabilization of rod phosphodiesterase, an enzyme essential for rod survival
      and function. However, little is understood regarding the role of AIPL1 in cone
      photoreceptors. Cone degeneration observed in the absence of AIPL1 could be due
      to an indirect 'bystander effect' caused by rod photoreceptor death or a direct
      role for AIPL1 in cones. To understand the importance of AIPL1 in cone
      photoreceptor cells, we transgenically expressed hAIPL1 exclusively in the rod
      photoreceptors of the Aipl1(-/-) mouse. Transgenic expression of hAIPL1 restored
      rod morphology and the rod-derived electroretinogram response, but cone
      photoreceptors were non-functional in the absence of AIPL1. In addition, the cone
      photoreceptors degenerate, but at a slower rate compared with Aipl1(-/-) mice.
      This degeneration is linked to the highly reduced levels of cone PDE6 observed in
      the hAIPL1 transgenic mice. Our studies demonstrate that AIPL1 is needed for the
      proper functioning and survival of cone photoreceptors. However, rod
      photoreceptors also provide support that partially preserves cone photoreceptors
      from rapid death in the absence of AIPL1.

PMID- 20042466
TI  - Dietary protein intake throughout childhood is associated with the timing of
      puberty.
AB  - Early puberty onset is associated with hormone-related cancers, but whether diet
      in childhood influences pubertal timing is controversial. We examined the
      association of protein intake in early and mid-childhood with the ages at take
      off of the pubertal growth spurt (ATO), peak height velocity (APHV), and menarche
      in girls and voice break in boys using data from the longitudinal Dortmund
      Nutritional and Anthropometric Longitudinally Designed Study. Among participants
      who provided 3-d weighed dietary records at 12 mo, 18-24 mo, 3-4 y, and 5-6 y,
      112 had sufficient anthropometric measurements between 6 and 13 y to allow
      estimation of ATO. Life-course plots were used to identify critical periods of
      total, animal, and vegetable protein intake (percentage of total energy intake)
      for pubertal timing. At these ages, the association between tertiles of protein
      intake (T1-T3) and the outcomes was investigated using multiple linear regression
      analysis. A higher total and animal protein intake at 5-6 y was related to an
      earlier ATO. In the highest tertile of animal protein intake at 5-6 y, ATO
      occurred 0.6 y earlier than in the lowest [(mean, 95% CI) T1: 9.6, 9.4-9.9 vs.
      T2: 9.4, 9.1-9.7 vs. T3: 9.0, 8.7-9.3 y; P-trend = 0.003, adjusted for sex, total
      energy, breast-feeding, birth year, and paternal university degree]. Similar
      findings were seen for APHV (P-trend = 0.001) and the timing of menarche/voice
      break (P-trend = 0.02). Conversely, a higher vegetable protein intake at 3-4 and
      5-6 y was related to later ATO, APHV, and menarche/voice break (P-trend = 0.02
      0.04). These results suggest that animal and vegetable protein intake in mid
      childhood might be differentially related to pubertal timing.

PMID- 20042467
TI  - Distinct populations of metastases-enabling myeloid cells expand in the liver of
      mice harboring invasive and preinvasive intra-abdominal tumor.
AB  - The liver is the most common site of adenocarcinoma metastases, even in patients
      who initially present with early disease. We postulated that immune-suppressive
      cells in the liver of tumor-bearing hosts inhibit anti-tumor T cells, thereby
      accelerating the growth of liver metastases. Using models of early preinvasive
      pancreatic neoplasia and advanced colorectal cancer, aims of this study were to
      determine immune phenotype, stimulus for recruitment, inhibitory effects, and
      tumor-enabling function of immune-suppressive cells in the liver of tumor-bearing
      hosts. We found that in mice with intra-abdominal malignancies, two distinct
      CD11b(+)Gr1(+) populations with divergent phenotypic and functional properties
      accumulate in the liver, becoming the dominant hepatic leukocytes. Their
      expansion is contingent on tumor expression of KC. These cells are distinct from
      CD11b(+)Gr1(+) populations in other tissues of tumor-bearing hosts in terms of
      cellular phenotype and cytokine and chemokine profile. Liver CD11b(+)Gr1(+) cells
      are highly suppressive of T cell activation, proliferation, and cytotoxicity and
      induce the development of Tregs. Moreover, liver myeloid-derived suppressor cells
      accelerate the development of hepatic metastases by inactivation of cytotoxic T
      cells. These findings may explain the propensity of patients with intra-abdominal
      cancers to develop liver metastases and suggest a promising target for
      experimental therapeutics.

PMID- 20042468
TI  - Macrophage polarization and HIV-1 infection.
AB  - Polarization of MP into classically activated (M1) and alternatively activated
      (M2a, M2b, and M2c) macrophages is critical in mediating an effective immune
      response against invading pathogens. However, several pathogens use these
      activation pathways to facilitate dissemination and pathogenesis. Viruses
      generally induce an M1-like phenotype during the acute phase of infection. In
      addition to promoting the development of Th1 responses and IFN production, M1
      macrophages often produce cytokines that drive viral replication and tissue
      damage. As shown for HIV-1, polarization can also alter macrophage susceptibility
      to infection. In vitro polarization into M1 cells prevents HIV-1 infection, and
      M2a polarization inhibits viral replication at a post-integration level. M2a
      cells also express high levels of C-type lectins that can facilitate macrophage
      mediated transmission of HIV-1 to CD4(+) T cells. Macrophages are particularly
      abundant in mucosal membranes and unlike DCs, do not usually migrate to distal
      tissues. As a result, macrophages are likely to contribute to HIV-1 pathogenesis
      in mucosal rather than lymphatic tissues. In vivo polarization of MP is likely to
      span a spectrum of activation phenotypes that may change the permissivity to and
      alter the outcome of HIV-1 and other viral infections.

PMID- 20042469
TI  - c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta
      inhibits c-Maf-induced IL-21 production in CD4+ T cells.
AB  - Previous studies have shown that IL-6 potently induces IL-21 production in CD4(+)
      T cells, whereas TGF-beta inhibits IL-6-induced IL-21 production in CD4(+) T
      cells. In this study, we addressed the mechanisms underlying the transcriptional
      regulation of IL-21 production in CD4(+) T cells. We found that IL-6 induced c
      Maf expression in CD4(+) T cells and that the enforced expression of c-Maf
      induced IL-21 production in CD4(+) T cells without IL-6, IL-4/STAT6 signaling, or
      an autocrine effect of IL-21. Moreover, we found that c-Maf directly bound to and
      activated IL-21P and the CNS-2 enhancer through MARE sites. On the other hand, we
      also found that although TGF-beta up-regulated IL-6-induced c-Maf expression in
      CD4(+) T cells, TGF-beta inhibited c-Maf-induced IL-21 production in CD4(+) T
      cells. Finally, we found that Foxp3 bound to IL-21P and the CNS-2 enhancer and
      inhibited c-Maf-induced IL-21 production modestly but significantly in CD4(+) T
      cells. Taken together, these results suggest that c-Maf induces IL-21 production
      directly in CD4(+) T cells by activating IL-21P and the CNS-2 enhancer and that
      TGF-beta suppresses c-Maf-induced IL-21 production in CD4(+) T cells.

PMID- 20042470
TI  - Mutz-3-derived Langerhans cells are a model to study HIV-1 transmission and
      potential inhibitors.
AB  - Sexual transmission is the primary route of HIV-1 infection, and DC subsets are
      thought to be involved in viral dissemination to T cells. In the genital mucosa,
      two main subsets of DCs are present: epithelial LCs capture and degrade HIV-1
      through C-type lectin Langerin, whereas subepithelial DCs express DC-SIGN, which
      facilitates HIV-1 transmission to T cells. As there is currently no HIV-1 vaccine
      available, microbicides provide an alternative strategy to limit HIV-1 spread.
      However, research into the function of LCs is hampered by the low availability
      and donor differences. Here, we set out to investigate whether LCs derived from
      the Mutz-3 cell line (Mu-LCs) provide a valuable tool to investigate the role of
      LCs in HIV-1 transmission and identify suitable potential microbicides. We
      demonstrate that Mu-LCs phenotypically resemble human primary LCs; Mu-LCs do not
      transmit HIV-1 efficiently, and inhibition of Langerin enhances HIV-1
      transmission to T cells. We show that carbohydrate structures blocking DC-SIGN
      but not Langerin are potential microbicides, as they prevent HIV-1 transmission
      by DCs but do not affect the antiviral function of LCs. Therefore, Mu-LCs are a
      suitable model to investigate the role of LCs in HIV-1 transmission and to screen
      potential microbicides.

PMID- 20042471
TI  - The role of macrophages in the development and progression of AIDS-related non
      Hodgkin lymphoma.
AB  - Despite HAART, patients infected with HIV develop NHL at a significantly higher
      level than the noninfected population. The primary difference between lymphoma in
      non-HIV-infected individuals and those with ARL is that ARL is consistently high
      grade and metastatic. The emergence of ARL is associated with the presence of
      macrophage viral reservoirs, similar to what has been observed for HAD. HIV
      infected macrophages, as seen by histology and HIV p24 staining, are present in
      approximately half of ARLs. Macrophage reservoirs recruit additional immune
      cells, including monocytes/macrophages, through the release of chemoattractants.
      Additionally, TAM are known to promote tumor progression for most cancer types,
      including lymphomas. This review will highlight and discuss the role of
      macrophage viral reservoirs in the development and progression of ARLs and
      hopefully, shed light on this new and interesting field.

PMID- 20042472
TI  - Restricted HIV-1 replication in placental macrophages is caused by inefficient
      viral transcription.
AB  - HIV-infected PM show restricted replication as compared with MDM. We aimed to
      determine at what point in the viral replication cycle this restriction occurs in
      PM as compared with MDM. We performed Alu-LTR PCR for proviral DNA to detect
      differences in HIV integration, real-time RT-PCR to measure env and gag mRNA
      levels, and Western blot analysis to detect differences in viral protein
      expression. PM and MDM were infected with HIV-1 BaL, and DNA was extracted after
      24 h and at 6 days p.i. for real-time PCR studies. At 6 and 12 days p.i., cells
      were lysed for Western blot analyses. We found no difference in viral integration
      between PM and MDM but significantly lower levels of viral protein gp120 in PM
      than in MDM. Real-time RT-PCR analyses revealed 24-fold less env mRNA and tenfold
      less gag mRNA in PM. These results suggest that HIV-1 restriction in PM occurs at
      the level of transcription. This study is significant, as it advances our
      understanding of HIV-1 infection in PM and its contribution to decreased in utero
      vertical transmission.

PMID- 20042473
TI  - Autoregulation of Fox protein expression to produce dominant negative splicing
      factors.
AB  - The Fox proteins are a family of regulators that control the alternative splicing
      of many exons in neurons, muscle, and other tissues. Each of the three mammalian
      paralogs, Fox-1 (A2BP1), Fox-2 (RBM9), and Fox-3 (HRNBP3), produces proteins with
      a single RNA-binding domain (RRM) flanked by N- and C-terminal domains that are
      highly diversified through the use of alternative promoters and alternative
      splicing patterns. These genes also express protein isoforms lacking the second
      half of the RRM (FoxDeltaRRM), due to the skipping of a highly conserved 93-nt
      exon. Fox binding elements overlap the splice sites of these exons in Fox-1 and
      Fox-2, and the Fox proteins themselves inhibit exon inclusion. Unlike other cases
      of splicing autoregulation by RNA-binding proteins, skipping the RRM exon creates
      an in-frame deletion in the mRNA to produce a stable protein. These FoxDeltaRRM
      isoforms expressed from cDNA exhibit highly reduced binding to RNA in vivo.
      However, we show that they can act as repressors of Fox-dependent splicing,
      presumably by competing with full-length Fox isoforms for interaction with other
      splicing factors. Interestingly, the Drosophila Fox homolog contains a nearly
      identical exon in its RRM domain that also has flanking Fox-binding sites. Thus,
      rather than autoregulation of splicing controlling the abundance of the
      regulator, the Fox proteins use a highly conserved mechanism of splicing
      autoregulation to control production of a dominant negative isoform.

PMID- 20042474
TI  - Anti-Argonaute RIP-Chip shows that miRNA transfections alter global patterns of
      mRNA recruitment to microribonucleoprotein complexes.
AB  - MicroRNAs (miRNAs) play key roles in gene expression regulation by guiding
      Argonaute (AGO)-containing microribonucleoprotein (miRNP) effector complexes to
      target polynucleotides. There are still uncertainties about how miRNAs interact
      with mRNAs. Here we employed a biochemical approach to isolate AGO-containing
      miRNPs from human H4 tumor cells by co-immunoprecipitation (co-IP) with a
      previously described anti-AGO antibody. Co-immunoprecipitated (co-IPed) RNAs were
      subjected to downstream Affymetrix Human Gene 1.0 ST microarray analysis. During
      rigorous validation, the "RIP-Chip" assay identified target mRNAs specifically
      associated with AGO complexes. RIP-Chip was performed after transfecting brain
      enriched miRNAs (miR-107, miR-124, miR-128, and miR-320) and nonphysiologic
      control miRNA to identify miRNA targets. As expected, the miRNA transfections
      altered the mRNA content of the miRNPs. Specific mRNA species recruited to miRNPs
      after miRNA transfections were moderately in agreement with computational target
      predictions. In addition to recruiting mRNA targets into miRNPs, miR-107 and to a
      lesser extent miR-128, but not miR-124 or miR-320, caused apparent exclusion of
      some mRNAs that are normally associated with miRNPs. MiR-107 and miR-128
      transfections also result in decreased AGO mRNA and protein levels. However, AGO
      mRNAs were not recruited to miRNPs after either miR-107 or miR-128 transfection,
      confirming that miRNAs may alter gene expression without stable association
      between particular mRNAs and miRNPs. In summary, RIP-Chip assays constitute an
      optimized, validated, direct, and high-throughput biochemical assay that provides
      data about specific miRNA:mRNA interactions, as well as global patterns of
      regulation by miRNAs.

PMID- 20042475
TI  - Effects of magnesium sulphate on intraoperative neuromuscular blocking agent
      requirements and postoperative analgesia in children with cerebral palsy.
AB  - BACKGROUND: In this double-blind, randomized, placebo-controlled study, we
      evaluated the effects of magnesium sulphate on neuromuscular blocking agent
      requirements and analgesia in children with cerebral palsy (CP). METHODS: We
      randomly divided 61 children with CP undergoing orthopaedic surgery into two
      groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg(-1)
      i.v. as a bolus and 15 mg kg(-1) h(-1) by continuous infusion during the
      operation. The control group (Group S) received the same amount of isotonic
      saline. Rocuronium was administered 0.6 mg kg(-1) before intubation and 0.1 mg
      kg(-1) additionally when train-of-four counts were 2 or more. I.V. fentanyl and
      ketorolac were used to control postoperative pain. Total infused analgesic
      volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and
      48 h. RESULTS: The rocuronium requirement of Group M was significantly less than
      that of Group S [0.29 (0.12) vs 0.42 (0.16) mg kg(-1) h(-1), P<0.05]. Cumulative
      analgesic consumption in Group M was significantly less after operation at 24 and
      48 h (P<0.05), and pain scores in Group M were lower than in Group S during the
      entire postoperative period (P<0.05). Serum magnesium concentrations in Group M
      were higher until 24 h after operation (P<0.05). The incidence of postoperative
      nausea and vomiting and rescue drug injections was similar in the two groups. No
      shivering or adverse effects related to hypermagnesaemia were encountered.
      CONCLUSIONS: I.V. magnesium sulphate reduces rocuronium requirements and
      postoperative analgesic consumption in children with CP.

PMID- 20042476
TI  - Confirmation of the ability to ventilate by facemask before administration of
      neuromuscular blocker: a non-instrumental piece of information?
AB  - BACKGROUND: Our aim was to determine whether anaesthetists routinely confirm
      their ability to ventilate a patient's lungs by a facemask before the
      administration of a neuromuscular blocker and the rationale for this practice.
      METHODS: An online survey of trainee and non-trainee anaesthetists working in
      hospitals forming part of the Central London School of Anaesthesia collected 136
      complete data sets over a 3 month period. RESULTS: Seventy-eight of 136 (57%)
      routinely checked they could ventilate by the facemask ('checkers'). The reasons
      given for this varied, though the most common was the ability to 'enable escape
      wake-up'. The practice was most commonly adopted by anaesthetists with less
      experience. In a hypothetical 'cannot ventilate' scenario, the use of
      succinylcholine was advocated by the majority of respondents, both 'checkers' and
      'non-checkers'. CONCLUSIONS: Despite the lack of firm evidence to support the
      practice of confirming the ability to ventilate the lungs before administering a
      neuromuscular blocking drug (NMB), we found strongly held views that supported
      the practice and equally strongly held views that opposed it. However, in a
      hypothetical emergency situation where ventilation by the facemask after
      induction of anaesthesia was impossible, the majority of respondents (including
      'checkers') would administer a neuromuscular blocker. This apparent paradox can
      be explained by well-recognized psychological mechanisms. We suggest that in
      checking the ability to ventilate by the facemask, some anaesthetists are seeking
      information that may be relevant but not instrumental in deciding when to
      administer an NMB.

PMID- 20042477
TI  - Comparison of early cognitive function and recovery after desflurane or
      sevoflurane anaesthesia in the elderly: a double-blinded randomized controlled
      trial.
AB  - BACKGROUND: Postoperative cognitive dysfunction (POCD) is being recognized as a
      complication contributing to perioperative morbidity and mortality of the
      elderly. We hypothesized that the use of the shorter-acting volatile anaesthetic
      desflurane would be associated with less incidence of POCD when compared with
      sevoflurane. METHODS: Approved by the local ethical committee, 80 patients (aged
      65-75 yr) were enrolled in this randomized, double-blinded study. Patients were
      allocated to either the desflurane (n=40) or the sevoflurane (n=40) group. The
      primary outcome was the cognitive Test for Attentional Performance with its
      subtests Alertness, Divided Attention, Visual Scanning, Working Memory, and
      Reaction Change. In addition, Paper-Pencil Tests [Well-being Test BF-S, Recall of
      Digit Span (DST), Digit-Symbol-Substitution Test, Trail Making Tests A and B, and
      Spielberg State-Trait Anxiety Inventory] were measured. After baseline assessment
      12-24 h before operation, patients were followed up 6-8 and 66-72 h after
      operation. Among other outcome parameters, emergence times from anaesthesia and
      modified Aldrete scores were recorded. RESULTS: There was no difference in the
      incidence of POCD. However, according to the Paper-Pencil Tests, significant
      improvements for the desflurane group could be detected (Well-being Test at 6-8
      h, DST at 6-8 h, and Trail Making Test at 66-72 h). Emergence was significantly
      faster in the desflurane group for 'time to open eyes' and 'time to extubation'.
      CONCLUSIONS: The total incidence of POCD showed no differences between the
      desflurane and the sevoflurane groups. However, the tests Well-being scale, DST,
      and Trail Making Test, emergence times, and patients' satisfaction were in favour
      of desflurane.

PMID- 20042478
TI  - Transdermal fentanyl for pain caused by radiotherapy in head and neck cancer
      patients treated in an outpatient setting: a multicenter trial in Taiwan.
AB  - OBJECTIVE: This study evaluated the efficacy and safety of transdermal fentanyl
      in the outpatient treatment of head and neck cancer patients with pain caused by
      radiotherapy. METHODS: Patients with a visual analogue scale score >or=4 were
      invited to participate in the study. The following variables were collected:
      visual analogue scale, the Brief Pain Inventory, concomitant pain medications and
      adverse effects. A total of 163 head and neck cancer patients were enrolled (148
      males and 15 females; median age, 53 years; age range, 21-72 years). Seventy-two
      (44%) patients had a visual analogue scale score >6 at enrollment, despite the
      use of non-steroidal anti-inflammatory drugs or weak opioids. Ninety-four (57.7%)
      patients received concurrent chemotherapy. RESULTS: A total of 88 patients
      completed the study, whereas 55 underwent a drop-out by side effects. The most
      frequently reported adverse events were vomiting (23.9%) and nausea (16.6%).
      Treatment with transdermal fentanyl resulted in a significant decrease in visual
      analogue scale and Brief Pain Inventory scores that persisted during treatment.
      In the overall efficacy evaluation, the pain-alleviating effect, the easiness of
      application and the overall impression of transdermal fentanyl were rated as good
      by 54.5%, 65.9% and 59.1% of the completers, respectively. Effects of transdermal
      fentanyl were rated as good by 64.8% of the investigators. CONCLUSIONS: Our data
      provide evidence that transdermal fentanyl is effective and relatively easy to
      use for outpatient treatment of pain control in head and neck cancer patients
      following radiotherapy in selected patients. Reduction of side effects and
      effective pain management need to be paramount in the management of head and neck
      cancer patients undergoing radiotherapy.

PMID- 20042479
TI  - ALP/Enigma PDZ-LIM domain proteins in the heart.
AB  - Actinin-associated LIM protein (ALP) and Enigma are two subfamilies of
      Postsynaptic density 95, discs large and zonula occludens-1 (PDZ)-Lin-11, Isl1
      and Mec-3 (LIM) domain containing proteins. ALP family members have one PDZ and
      one LIM domain, whereas Enigma proteins contain one PDZ and three LIM domains.
      Four ALP and three Enigma proteins have been identified in mammals, each having
      multiple splice variants and unique expression patterns. Functionally, these
      proteins bind through their PDZ domains to alpha-actinin and bind through their
      LIM domains or other internal protein interaction domains to other proteins,
      including signaling molecules. ALP and Enigma proteins have been implicated in
      cardiac and skeletal muscle structure, function and disease, neuronal function,
      bipolar disorder, tumor growth, platelet and epithelial cell motility and bone
      formation. This review will focus on recent advances in the biological roles of
      ALP/Enigma PDZ-LIM domain proteins in cardiac muscle and provide insights into
      mechanisms by which mutations in these proteins are related to human cardiac
      disease.

PMID- 20042480
TI  - Social modulation of learning in rats.
AB  - It is well known that emotions participate in the regulation of social behaviors
      and that the emotion displayed by a conspecific influences the behavior of other
      animals. In its simplest form, empathy can be characterized as the capacity to be
      affected by and/or share the emotional state of another. However, to date,
      relatively little is known about the mechanisms by which animals that are not in
      direct danger share emotions. In the present study, we used a model of between
      subject transfer of fear to characterize the social interaction during which fear
      is transmitted, as well as the behavioral effects of socially transmitted fear.
      We found that (1) during social interaction with a recently fear-conditioned
      partner, observers and demonstrators exhibit social exploratory behaviors rather
      than aggressive behaviors; (2) learning and memory in a shock-motivated shuttle
      avoidance task are facilitated in rats that underwent a social interaction with a
      partner that had been fear conditioned; and (3) a brief social interaction with a
      recently fear-conditioned partner immediately before fear conditioning increases
      conditioned freezing measured on the next day. The observed effects were not due
      to a stress-induced increase in pain sensitivity or analgesia. Collectively,
      these data suggest that a brief social interaction with a cage mate that has
      undergone an aversive learning experience promotes aversive learning in an
      otherwise naive animal. We argue that socially transferred fear is an adaptation
      that promotes defensive behavior to potentially dangerous situations in the
      environment.

PMID- 20042481
TI  - Endogenous cannabinoids trigger the depolarization-induced suppression of
      excitation in the lateral amygdala.
AB  - The amygdala is a key area of the brain where the emotional memories are stored
      throughout the lifespan. It is well established that synapses in the lateral
      nucleus of amygdala (LA) can undergo long-term potentiation, a putative cellular
      correlate of learning and memory. However, a type of short-term synaptic
      plasticity, known as depolarization-induced suppression of excitation (DSE), has
      not been studied previously in the amygdala in general and in the LA in
      particular. In this study we aimed to prove either the absence or the presence of
      this phenomenon in the LA. Our data demonstrate for the first time that DSE is
      present in the LA and that it modulates the cortical excitatory synaptic input
      into this region. The existence of this type of retrograde neurotransmission in
      glutamatergic pyramidal neurons of the LA suggests that the axonal terminals of
      cortical inputs do possess functional type 1 cannabinoid receptors, and provides
      a novel insight regarding inputs into the LA. Further experiments indeed revealed
      endocannabinoids as the messenger for this retrograde signaling in the LA. In
      conclusion, the DSE may play a functional role in synaptic plasticity and related
      emotional memory processing in the LA.

PMID- 20042483
TI  - Ten steps towards improving prognosis research.

PMID- 20042482
TI  - Nitric oxide and histamine signal attempts to swallow: A component of learning
      that food is inedible in Aplysia.
AB  - Memory that food is inedible in Aplysia arises from training requiring three
      contingent events. Nitric oxide (NO) and histamine are released by a neuron
      responding to one of these events, attempts to swallow food. Since NO release
      during training is necessary for subsequent memory and NO substitutes for
      attempts to swallow, it was suggested that NO functions during training as a
      signal of attempts to swallow. However, it has been shown that NO may also be
      released in other contexts affecting feeding, raising the possibility that its
      role in learning is unrelated to signaling attempts to swallow. We confirmed that
      NO during learning signals attempts to swallow, by showing that a variety of
      behavioral effects on feeding of blocking or adding NO do not affect learning and
      memory that a food is inedible. In addition, histamine had effects similar to NO
      on learning that food is inedible, as expected if the transmitters are released
      together when animals attempt to swallow. Blocking histamine during training
      blocked long-term memory, and exogenous histamine substituted for attempts to
      swallow. NO also substituted for histamine during training. Histamine at
      concentrations relevant to learning activates neuron metacerebral cell (MCC).
      However, MCC activity is not a good monitor of attempts to swallow during
      training, since the neuron responds equally well to other stimuli. These findings
      support and extend the hypothesis that NO and histamine signal efforts to swallow
      during learning, acting on targets other than the MCC that specifically respond
      to attempts to swallow.

PMID- 20042484
TI  - The vomiting baby.

PMID- 20042485
TI  - Working time regulations for trainee doctors. Wendy Reid replies to Roy Pounder.

PMID- 20042486
TI  - Flank pain and haematuria.

PMID- 20042490
TI  - Letting go. Time to rethink CPR.

PMID- 20042491
TI  - Doctors' hours. Consider physicians' training.

PMID- 20042492
TI  - "Greenwash" at the climate change summit in Copenhagen.

PMID- 20042493
TI  - Cervical cancer virus can be transmitted through same sex relationships, report
      warns.

PMID- 20042495
TI  - Epstein-Barr virus-encoded Bcl-2 homologue functions as a survival factor in Wp
      restricted Burkitt lymphoma cell line P3HR-1.
AB  - Burkitt lymphoma (BL) is etiologically associated with Epstein-Barr virus (EBV).
      EBV-positive BL tumors display two latent forms of infection. One is referred to
      as latency I infection, in which EBV expresses the virus genome maintenance
      protein EBNA1 as the only viral protein. The other is referred to as Wp
      restricted latency and was recently identified in a subset of BL tumors. In these
      tumors, EBV expresses EBNA1, EBNA3A, EBNA3B, EBNA3C, a truncated form of EBNA-LP,
      and the viral Bcl-2 homologue BHRF1, all of which are driven by the BamHI W
      promoter (Wp). To investigate the role of EBV in Wp-restricted BL, we
      conditionally expressed a dominant-negative EBNA1 (dnEBNA1) mutant which
      interrupts the virus genome maintenance function of EBNA1 in the P3HR-1 BL cell
      line. Induction of dnEBNA1 expression caused loss of the EBV genome and resulted
      in apoptosis of P3HR-1 cells in the absence of exogenous apoptosis inducers,
      indicating that P3HR-1 cells cannot survive without EBV. Stable transfection of
      the BHRF1 gene into P3HR-1 cells rescued the cells from the apoptosis induced by
      dnEBNA1 expression, whereas stable transfection of truncated EBNA-LP, EBNA3A, or
      EBNA3C did not. Moreover, knockdown of BHRF1 expression in P3HR-1 cells resulted
      in increased cell death. These results indicate that EBV is essential for the
      survival of P3HR-1 cells and that BHRF1 functions as a survival factor. Our
      finding implies a critical contribution of BHRF1 to the pathogenesis of Wp
      restricted BLs.

PMID- 20042496
TI  - The capsid proteins of Aleutian mink disease virus activate caspases and are
      specifically cleaved during infection.
AB  - Aleutian mink disease virus (AMDV) is currently the only known member of the
      genus Amdovirus in the family Parvoviridae. It is the etiological agent of
      Aleutian disease of mink. We have previously shown that a small protein with a
      molecular mass of approximately 26 kDa was present during AMDV infection and
      following transfection of capsid expression constructs (J. Qiu, F. Cheng, L. R.
      Burger, and D. Pintel, J. Virol. 80:654-662, 2006). In this study, we report that
      the capsid proteins were specifically cleaved at aspartic acid residue 420 (D420)
      during virus infection, resulting in the previously observed cleavage product.
      Mutation of a single amino acid residue at D420 abolished the specific cleavage.
      Expression of the capsid proteins alone in Crandell feline kidney (CrFK) cells
      reproduced the cleavage of the capsid proteins in virus infection. More
      importantly, capsid protein expression alone induced active caspases, of which
      caspase-10 was the most active. Active caspases, in turn, cleaved capsid proteins
      in vivo. Our results also showed that active caspase-7 specifically cleaved
      capsid proteins at D420 in vitro. These results suggest that viral capsid
      proteins alone induce caspase activation, resulting in cleavage of capsid
      proteins. We also provide evidence that AMDV mutants resistant to caspase
      mediated capsid cleavage increased virus production approximately 3- to 5-fold in
      CrFK cells compared to that produced from the parent virus AMDV-G at 37 degrees C
      but not at 31.8 degrees C. Collectively, our results indicate that caspase
      activity plays multiple roles in AMDV infection and that cleavage of the capsid
      proteins might have a role in regulating persistent infection of AMDV.

PMID- 20042497
TI  - GLTSCR2/PICT-1, a putative tumor suppressor gene product, induces the nucleolar
      targeting of the Kaposi's sarcoma-associated herpesvirus KS-Bcl-2 protein.
AB  - KS-Bcl-2, encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), is a
      structural and functional homologue of the Bcl-2 family of apoptosis regulators.
      Like several other Bcl-2 family members, KS-Bcl-2 protects cells from apoptosis
      and autophagy. Using a yeast two-hybrid screen and coimmunoprecipitation assays,
      we identified a novel KS-Bcl-2-interacting protein, referred to as protein
      interacting with carboxyl terminus 1 (PICT-1), encoded by a candidate tumor
      suppressor gene, GLTSCR2. Confocal laser scanning microscopy revealed nucleolar
      localization of PICT-1, whereas KS-Bcl-2 was located mostly at the mitochondrial
      membranes with a small fraction in the nucleoli. Ectopic expression of PICT-1
      resulted in a large increase in the nucleolar fraction of KS-Bcl-2, and only a
      minor fraction remained in the cytoplasm. Furthermore, knockdown of endogenous
      PICT-1 abolished the nucleolar localization of KS-Bcl-2. However, ectopically
      expressed PICT-1 did not alter the cellular distribution of human Bcl-2.
      Subsequent analysis mapped the crucial amino acid sequences of both KS-Bcl-2 and
      PICT-1 required for their interaction and for KS-Bcl-2 targeting to the
      nucleolus. Functional studies suggest a correlation between nucleolar targeting
      of KS-Bcl-2 by PICT-1 and reduction of the antiapoptotic activity of KS-Bcl-2.
      Thus, these studies demonstrate a cellular mechanism to sequester KS-Bcl-2 from
      the mitochondria and to downregulate its virally encoded antiapoptotic activity.
      Additional characterization of the interaction of KS-Bcl-2 and PICT-1 is likely
      to shed light on the functions of both proteins.

PMID- 20042498
TI  - Inability of plasmacytoid dendritic cells to directly lyse HIV-infected
      autologous CD4+ T cells despite induction of tumor necrosis factor-related
      apoptosis-inducing ligand.
AB  - The function of plasmacytoid dendritic cells (PDC) in chronic human
      immunodeficiency virus type 1 (HIV-1) infection remains controversial with regard
      to its potential for sustained alpha interferon (IFN-alpha) production and
      induction of PDC-dependent tumor necrosis factor (TNF)-related apoptosis-inducing
      ligand (TRAIL)-mediated cytotoxicity of HIV-infected cells. We address these
      areas by a study of chronically HIV-1-infected subjects followed through
      antiretroviral therapy (ART) interruption and by testing PDC cytolytic function
      against autologous HIV-infected CD4(+) T cells. Rebound in viremia induced by
      therapy interruption showed a positive association between TRAIL and viral load
      or T-cell activation, but comparable levels of plasma IFN-alpha/beta were found
      in viremic ART-treated and control subjects. While PDC from HIV-infected subjects
      expressed less interferon regulator factor 7 (IRF-7) and produced significantly
      less IFN-alpha upon Toll-like receptor 7/9 (TLR7/9) engagement than controls,
      membrane TRAIL expression in PDC from HIV(+) subjects was increased. Moreover, no
      significant increase in death receptor 5 (DR5) expression was seen in CD4(+) T
      cells from viremic HIV(+) subjects compared to controls or following in vitro
      infection/exposure to infectious and noninfectious virus or exogenous IFN-alpha,
      respectively. Although activated PDC killed the DR5-expressing HIV-infected Sup
      T1 cell line, PDC did not lyse primary autologous HIV(+) CD4(+) T cells yet could
      provide accessory help for NK cells in killing HIV-infected autologous CD4(+) T
      cells. Taken together, our data show a lack of sustained high levels of soluble
      IFN-alpha in chronic HIV-1 infection in vivo and document a lack of direct PDC
      cytolytic activity against autologous infected or uninfected CD4(+) T cells.

PMID- 20042499
TI  - Effect of mutations in the human immunodeficiency virus type 1 protease on
      cleavage of the gp41 cytoplasmic tail.
AB  - We previously reported that human immunodeficiency virus type 1 (HIV-1) develops
      resistance to the cholesterol-binding compound amphotericin B methyl ester (AME)
      by acquiring mutations (P203L and S205L) in the cytoplasmic tail of the
      transmembrane envelope glycoprotein gp41 that create cleavage sites for the viral
      protease (PR). In the present study, we observed that a PR inhibitor-resistant
      (PIR) HIV-1 mutant is unable to efficiently cleave the gp41 cytoplasmic tail in
      P203L and S205L virions, resulting in loss of AME resistance. To define the
      pathway to AME resistance in the context of the PIR PR, we selected for
      resistance with an HIV-1 isolate expressing the mutant enzyme. We identified a
      new gp41 mutation, R236L, that results in cleavage of the gp41 tail by the PIR
      PR. These results highlight the central role of gp41 cleavage as the primary
      mechanism of AME resistance.

PMID- 20042500
TI  - Interaction domains of the UL16 and UL21 tegument proteins of herpes simplex
      virus.
AB  - The UL16 protein of herpes simplex virus is capsid associated and was previously
      identified as a binding partner of the membrane-associated UL11 tegument protein
      (J. S. Loomis, R. J. Courtney, and J. W. Wills, J. Virol. 77:11417-11424, 2003).
      In those studies, a less-prominent, approximately 65-kDa binding partner of
      unknown identity was also observed. Mass spectrometry studies have now revealed
      this species to be UL21, a tegument protein that has been implicated in the
      transport of capsids in the cytoplasm. The validity of the mass spectrometry
      results was tested in a variety of coimmunoprecipitation and glutathione S
      transferase pull-down experiments. The data revealed that UL21 and UL16 can form
      a complex in the absence of other viral proteins, even when the assays used
      proteins purified from Escherichia coli. Moreover, UL11 was able to pull down
      UL21 only when UL16 was present, suggesting that all three proteins can form a
      complex. Deletion analyses revealed that the second half of UL21 (residues 268 to
      535) is sufficient for the UL16 interaction and packaging into virions; however,
      attempts to map a subdomain of UL16 were largely unsuccessful, with only the
      first 40 (of 373) residues being found to be dispensable. Nevertheless, it is
      clear that UL16 must have two distinct binding sites, because covalent
      modification of its free cysteines with N-ethylmaleimide blocked binding to UL11
      but not UL21. These findings should prove useful for elucidating the molecular
      machinery used to transmit a signal into a virion when it attaches to cells, a
      recently discovered mechanism in which UL16 is a central player.

PMID- 20042501
TI  - Measles virus infection of alveolar macrophages and dendritic cells precedes
      spread to lymphatic organs in transgenic mice expressing human signaling
      lymphocytic activation molecule (SLAM, CD150).
AB  - Recent studies of primate models suggest that wild-type measles virus (MV)
      infects immune cells located in the airways before spreading systemically, but
      the identity of these cells is unknown. To identify cells supporting primary MV
      infection, we took advantage of mice expressing the MV receptor human signaling
      lymphocyte activation molecule (SLAM, CD150) with human-like tissue specificity.
      We infected these mice intranasally (IN) with a wild-type MV expressing green
      fluorescent protein. One, two, or three days after inoculation, nasal-associated
      lymphoid tissue (NALT), the lungs, several lymph nodes (LNs), the spleen, and the
      thymus were collected and analyzed by microscopy and flow cytometry, and virus
      isolation was attempted. One day after inoculation, MV replication was documented
      only in the airways, in about 2.5% of alveolar macrophages (AM) and 0.5% of
      dendritic cells (DC). These cells expressed human SLAM, and it was observed that
      MV infection temporarily enhanced SLAM expression. Later, MV infected other
      immune cell types, including B and T lymphocytes. Virus was isolated from
      lymphatic tissue as early as 2 days post-IN inoculation; the mediastinal lymph
      node was an early site of replication and supported high levels of infection.
      Three days after intraperitoneal inoculation, 1 to 8% of the mediastinal LN cells
      were infected. Thus, MV infection of alveolar macrophages and subepithelial
      dendritic cells in the airways precedes infection of lymphocytes in lymphatic
      organs of mice expressing human SLAM with human-like tissue specificity.

PMID- 20042502
TI  - Serotype-specific structural differences in the protease-cofactor complexes of
      the dengue virus family.
AB  - With an estimated 40% of the world population at risk, dengue poses a significant
      threat to human health, especially in tropical and subtropical regions.
      Preventative and curative efforts, such as vaccine development and drug
      discovery, face additional challenges due to the occurrence of four antigenically
      distinct serotypes of the causative dengue virus (DEN1 to -4). Complex immune
      responses resulting from repeat assaults by the different serotypes necessitate
      simultaneous targeting of all forms of the virus. One of the promising targets
      for drug development is the highly conserved two-component viral protease NS2B
      NS3, which plays an essential role in viral replication by processing the viral
      precursor polyprotein into functional proteins. In this paper, we report the 2.1
      A crystal structure of the DEN1 NS2B hydrophilic core (residues 49 to 95) in
      complex with the NS3 protease domain (residues 1 to 186) carrying an internal
      deletion in the N terminus (residues 11 to 20). While the overall folds within
      the protease core are similar to those of DEN2 and DEN4 proteases, the
      conformation of the cofactor NS2B is dramatically different from those of other
      flaviviral apoprotease structures. The differences are especially apparent within
      its C-terminal region, implicated in substrate binding. The structure reveals for
      the first time serotype-specific structural elements in the dengue virus family,
      with the reported alternate conformation resulting from a unique metal-binding
      site within the DEN1 sequence. We also report the identification of a 10-residue
      stretch within NS3pro that separates the substrate-binding function from the
      catalytic turnover rate of the enzyme. Implications for broad-spectrum drug
      discovery are discussed.

PMID- 20042503
TI  - Identification of an ICP27-responsive element in the coding region of a herpes
      simplex virus type 1 late gene.
AB  - During productive herpes simplex virus type 1 (HSV-1) infection, a subset of
      viral delayed-early (DE) and late (L) genes require the immediate-early (IE)
      protein ICP27 for their expression. However, the cis-acting regulatory sequences
      in DE and L genes that mediate their specific induction by ICP27 are unknown. One
      viral L gene that is highly dependent on ICP27 is that encoding glycoprotein C
      (gC). We previously demonstrated that this gene is posttranscriptionally
      transactivated by ICP27 in a plasmid cotransfection assay. Based on our past
      results, we hypothesized that the gC gene possesses a cis-acting inhibitory
      sequence and that ICP27 overcomes the effects of this sequence to enable
      efficient gC expression. To test this model, we systematically deleted sequences
      from the body of the gC gene and tested the resulting constructs for expression.
      In so doing, we identified a 258-bp "silencing element" (SE) in the 5' portion of
      the gC coding region. When present, the SE inhibits gC mRNA accumulation from a
      transiently transfected gC gene, unless ICP27 is present. Moreover, the SE can be
      transferred to another HSV-1 gene, where it inhibits mRNA accumulation in the
      absence of ICP27 and confers high-level expression in the presence of ICP27.
      Thus, for the first time, an ICP27-responsive sequence has been identified in a
      physiologically relevant ICP27 target gene. To see if the SE functions during
      viral infection, we engineered HSV-1 recombinants that lack the SE, either in a
      wild-type (WT) or ICP27-null genetic background. In an ICP27-null background,
      deletion of the SE led to ICP27-independent expression of the gC gene,
      demonstrating that the SE functions during viral infection. Surprisingly, the
      ICP27-independent gC expression seen with the mutant occurred even in the absence
      of viral DNA synthesis, indicating that the SE helps to regulate the tight DNA
      replication-dependent expression of gC.

PMID- 20042504
TI  - Evolution of the HIV-1 env gene in the Rag2-/- gammaC-/- humanized mouse model.
AB  - Rag2(-/-) gamma(C)(-/-) mice transplanted with human hematopoietic stem cells
      (DKO-hu-HSC mice) mimic aspects of human infection with human immunodeficiency
      virus type 1 (HIV-1), including sustained viral replication and CD4(+) T-cell
      decline. However, the extent of HIV-1 evolution during long-term infection in
      these humanized mice, a key feature of the natural infection, has not been
      assessed fully. In this study, we examined the types of genotypic and phenotypic
      changes in the viral env gene that occur in the viral populations of DKO-hu-HSC
      mice infected with the CCR5-tropic isolate HIV-1(JRCSF) for up to 44 weeks. The
      mean rate of divergence of viral populations in mice was similar to that observed
      in a cohort of humans during a similar period of infection. Many amino acid
      substitutions were common across mice, including losses of N-linked glycosylation
      sites and substitutions in the CD4 binding site and in CD4-induced epitopes,
      indicating common selective pressures between mice. In addition, env variants
      evolved sensitivity to antibodies directed at V3, suggesting a more open
      conformation for Env. This phenotypic change was associated with increased CD4
      binding efficiency and was attributed to specific amino acid substitutions. In
      one mouse, env variants emerged that exhibited a CXCR4-tropic phenotype. These
      sequences were compartmentalized in the mesenteric lymph node. In summary, viral
      populations in these mice exhibited dynamic behavior that included sequence
      evolution, compartmentalization, and the appearance of distinct phenotypic
      changes. Thus, humanized mice offer a useful model for studying evolutionary
      processes of HIV-1 in a complex host environment.

PMID- 20042505
TI  - Pseudotyping incompatibility between HIV-1 and gibbon ape leukemia virus Env is
      modulated by Vpu.
AB  - The Env protein from gibbon ape leukemia virus (GaLV) has been shown to be
      incompatible with human immunodeficiency virus type 1 (HIV-1) in the production
      of infectious pseudotyped particles. This incompatibility has been mapped to the
      C-terminal cytoplasmic tail of GaLV Env. Surprisingly, we found that the HIV-1
      accessory protein Vpu modulates this incompatibility. The infectivity of HIV-1
      pseudotyped with murine leukemia virus (MLV) Env was not affected by Vpu.
      However, the infectivity of HIV-1 pseudotyped with an MLV Env with the
      cytoplasmic tail from GaLV Env (MLV/GaLV Env) was restricted 50- to 100-fold by
      Vpu. A Vpu mutant containing a scrambled membrane-spanning domain, Vpu(RD), was
      still able to restrict MLV/GaLV Env, but mutation of the serine residues at
      positions 52 and 56 completely alleviated the restriction. Loss of infectivity
      appeared to be caused by reduced MLV/GaLV Env incorporation into viral particles.
      The mechanism of this downmodulation appears to be distinct from Vpu-mediated CD4
      downmodulation because Vpu-expressing cells that failed to produce infectious HIV
      1 particles nonetheless continued to display robust surface MLV/GaLV Env
      expression. In addition, if MLV and HIV-1 were simultaneously introduced into the
      same cells, only the HIV-1 particle infectivity was restricted by Vpu.
      Collectively, these data suggest that Vpu modulates the cellular distribution of
      MLV/GaLV Env, preventing its recruitment to HIV-1 budding sites.

PMID- 20042506
TI  - Evidence for multiple recent host species shifts among the Ranaviruses (family
      Iridoviridae).
AB  - Members of the genus Ranavirus (family Iridoviridae) have been recognized as
      major viral pathogens of cold-blooded vertebrates. Ranaviruses have been
      associated with amphibians, fish, and reptiles. At this time, the relationships
      between ranavirus species are still unclear. Previous studies suggested that
      ranaviruses from salamanders are more closely related to ranaviruses from fish
      than they are to ranaviruses from other amphibians, such as frogs. Therefore, to
      gain a better understanding of the relationships among ranavirus isolates, the
      genome of epizootic hematopoietic necrosis virus (EHNV), an Australian fish
      pathogen, was sequenced. Our findings suggest that the ancestral ranavirus was a
      fish virus and that several recent host shifts have taken place, with subsequent
      speciation of viruses in their new hosts. The data suggesting several recent host
      shifts among ranavirus species increase concern that these pathogens of cold
      blooded vertebrates may have the capacity to cross numerous poikilothermic
      species barriers and the potential to cause devastating disease in their new
      hosts.

PMID- 20042507
TI  - Activation of peroxisome proliferator-activated receptor gamma by human
      cytomegalovirus for de novo replication impairs migration and invasiveness of
      cytotrophoblasts from early placentas.
AB  - Human cytomegalovirus (HCMV) contributes to pathogenic processes in
      immunosuppressed individuals, in fetuses, and in neonates. In the present report,
      by using reporter gene activation assays and confocal microscopy in the presence
      of a specific antagonist, we show for the first time that HCMV infection induces
      peroxisome proliferator-activated receptor gamma (PPARgamma) transcriptional
      activity in infected cells. We demonstrate that the PPARgamma antagonist
      dramatically impairs virus production and that the major immediate-early promoter
      contains PPAR response elements able to bind PPARgamma, as assessed by
      electrophoretic mobility shift and chromatin immunoprecipitation assays. Due to
      the key role of PPARgamma in placentation and its specific trophoblast expression
      within the human placenta, we then provided evidence that by activating PPARgamma
      human cytomegalovirus dramatically impaired early human trophoblast migration and
      invasiveness, as assessed by using well-established in vitro models of invasive
      trophoblast, i.e., primary cultures of extravillous cytotrophoblasts (EVCT)
      isolated from first-trimester placentas and the EVCT-derived cell line HIPEC. Our
      data provide new clues to explain how early infection during pregnancy could
      impair implantation and placentation and therefore embryonic development.

PMID- 20042508
TI  - Rapid dissociation of HIV-1 from cultured cells severely limits infectivity
      assays, causes the inactivation ascribed to entry inhibitors, and masks the
      inherently high level of infectivity of virions.
AB  - By using immunofluorescence microscopy to observe and analyze freshly made HIV-1
      virions adsorbed onto cells, we found that they are inherently highly infectious,
      rather than predominantly defective as previously suggested. Surprisingly,
      polycations enhance titers 20- to 30-fold by stabilizing adsorption and
      preventing a previously undescribed process of rapid dissociation, strongly
      implying that infectivity assays for many viruses are limited not only by
      inefficient virus diffusion onto cells but also by a postattachment race between
      entry and dissociation. This kinetic competition underlies inhibitory effects of
      CCR5 antagonists and explains why adaptive HIV-1 mutations overcome many cell
      entry limitations by accelerating entry.

PMID- 20042509
TI  - Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency
      virus challenge.
AB  - The prophylactic efficacies of several multivalent replication-incompetent
      adenovirus serotype 5 (Ad5) vaccines were examined in rhesus macaques using an
      intrarectal high-dose simian immunodeficiency virus SIVmac239 challenge model.
      Cohorts of Mamu-A*01(+)/B*17(-) Indian rhesus macaques were immunized with one of
      several combinations of Ad5 vectors expressing Gag, Pol, Nef, and Env gp140; for
      comparison, a Mamu-A*01(+) cohort was immunized using the Ad5 vector alone. There
      was no sign of immunological interference between antigens in the immunized
      animals. In general, expansion of the antigen breadth resulted in more favorable
      virological outcomes. In particular, the order of efficacy trended as follows:
      Gag/Pol/Nef/Env approximately Gag/Pol > Gag approximately Gag/Pol/Nef > Nef.
      However, the precision in ranking the vaccines based on the study results may be
      limited by the cohort size, and as such, may warrant additional testing. The
      implications of these results in light of the recent discouraging results of the
      phase IIb study of the trivalent Ad5 HIV-1 vaccine are discussed.

PMID- 20042510
TI  - Gamma interferon signaling in oligodendrocytes is critical for protection from
      neurotropic coronavirus infection.
AB  - Neurotropic coronavirus induces acute encephalomyelitis and demyelination in
      mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma
      interferon (IFN-gamma) receptor specifically in oligodendrocytes was examined to
      determine the influence of IFN-gamma signaling on pathogenesis. Inhibition of IFN
      gamma signaling in oligodendrocytes increased viral load, infection of
      oligodendrocytes, oligodendrocyte loss, demyelination, and axonal damage
      resulting in increased mortality. IFN-gamma levels and the inflammatory response
      were not altered, although the level of tumor necrosis factor (TNF) mRNA was
      increased. These data indicate that IFN-gamma signaling by oligodendroglia
      reduces viral replication but affects both demyelination and tissue destruction
      in a host-specific manner.

PMID- 20042511
TI  - Naturally occurring human monoclonal antibodies neutralize both 1918 and 2009
      pandemic influenza A (H1N1) viruses.
AB  - The 2009 pandemic influenza A (H1N1) virus exhibits hemagglutinin protein
      sequence homology with the 1918 pandemic influenza virus. We found that human
      monoclonal antibodies recognized the Sa antigenic site on the head domains of
      both 1918 and 2009 hemagglutinins, a site that is hypervariable due to immune
      selection. These antibodies exhibited high potency against the 2009 virus in
      vitro, and one exerted a marked therapeutic effect in vivo.

PMID- 20042512
TI  - Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of
      its heavy chain third complementarity-determining region.
AB  - The membrane-proximal external region (MPER) of the HIV-1 gp41 transmembrane
      glycoprotein is the target of the broadly neutralizing antibody 2F5. Prior
      studies have suggested a two-component mechanism for 2F5-mediated neutralization
      involving both structure-specific recognition of a gp41 protein epitope and
      nonspecific interaction with the viral lipid membrane. Here, we mutationally
      alter a hydrophobic patch on the third complementarity-determining region of the
      heavy chain (CDR H3) of the 2F5 antibody and assess the abilities of altered 2F5
      variants to bind gp41 and to neutralize diverse strains of HIV-1. CDR H3
      alterations had little effect on the affinity of 2F5 variants for a peptide
      corresponding to its gp41 epitope. In contrast, strong effects and a high degree
      of correlation (P < 0.0001) were found between virus neutralization and CDR H3
      hydrophobicity, as defined by predicted free energies of transfer from water to a
      lipid bilayer interface or to octanol. The effect of CDR H3 hydrophobicity on
      neutralization was independent of isolate sensitivity to 2F5, and CDR H3 variants
      with tryptophan substitutions were able to neutralize HIV-1 approximately 10-fold
      more potently than unmodified 2F5. A threshold was observed for increased
      hydrophobicity of the 2F5 CDR H3 loop beyond which effects on 2F5-mediated
      neutralization leveled off. Together, the results provide a more complete
      understanding of the 2F5 mechanism of HIV-1 neutralization and indicate ways to
      enhance the potency of MPER-directed antibodies.

PMID- 20042513
TI  - Proteasome subunits relocalize during human cytomegalovirus infection, and
      proteasome activity is necessary for efficient viral gene transcription.
AB  - We have continued studies to further understand the role of the ubiquitin
      proteasome system (UPS) in human cytomegalovirus (HCMV) infection. With specific
      inhibitors of the proteasome, we show that ongoing proteasome activity is
      necessary for facilitating the various stages of the infection. Immediate-early
      protein 2 expression is modestly reduced with addition of proteasome inhibitors
      at the onset of infection; however, both early and late gene expression are
      significantly delayed, even if the inhibitor is removed at 12 h postinfection.
      Adding the inhibitor at later times during the infection blocks the further
      accumulation of viral early and late gene products, the severity of which is
      dependent on when the proteasome is inhibited. This can be attributed primarily
      to a block in viral RNA transcription, although DNA synthesis is also partially
      inhibited. Proteasome activity and expression increase as the infection
      progresses, and this coincides with the relocalization of active proteasomes to
      the periphery of the viral DNA replication center, where there is active RNA
      transcription. Interestingly, one 19S subunit, Rpn2, is specifically recruited
      into the viral DNA replication center. The relocalization of the subunits
      requires viral DNA replication, but their maintenance around or within the
      replication center is not dependent on continued viral DNA synthesis or the
      proteolytic activity of the proteasome. These studies highlight the importance of
      the UPS at all stages of the HCMV infection and support further studies into this
      pathway as a potential antiviral target.

PMID- 20042514
TI  - Canine distemper viruses expressing a hemagglutinin without N-glycans lose
      virulence but retain immunosuppression.
AB  - Paramyxovirus glycoproteins are posttranslationally modified by the addition of N
      linked glycans, which are often necessary for correct folding, processing, and
      cell surface expression. To establish the contribution of N glycosylation to
      morbillivirus attachment (H) protein function and overall virulence, we first
      determined the use of the potential N-glycosylation sites in the canine distemper
      virus (CDV) H proteins. Biochemical characterization revealed that the three
      sites conserved in all strains were N glycosylated, whereas only two of the up to
      five additional sites present in wild-type strains are used. A wild-type virus
      with an H protein reproducing the vaccine strain N-glycosylation pattern remained
      lethal in ferrets but with a prolonged course of disease. In contrast,
      introduction of the vaccine H protein in the wild-type context resulted in
      complete attenuation. To further characterize the role of N glycosylation in CDV
      pathogenesis, the N-glycosylation sites of wild-type H proteins were successively
      deleted, including a nonstandard site, to ultimately generate a nonglycosylated H
      protein. Despite reduced expression levels, this protein remained fully
      functional. Recombinant viruses expressing N-glycan-deficient H proteins no
      longer caused disease, even though their immunosuppressive capacities were
      retained, indicating that reduced N glycosylation contributes to attenuation
      without affecting immunosuppression.

PMID- 20042515
TI  - Role of Rad51 down-regulation and extracellular signal-regulated kinases 1 and 2
      inactivation in emodin and mitomycin C-induced synergistic cytotoxicity in human
      non-small-cell lung cancer cells.
AB  - Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a natural anthraquinone
      derivative found in the roots and rhizomes of numerous plants. It is a tyrosine
      kinase inhibitor and has anticancer effects on lung cancer. Rad51 plays a central
      role in homologous recombination, and high levels of Rad51 expression are
      observed in chemo- or radioresistant carcinomas. Our previous studies have shown
      that the mitogen-activated protein kinase kinase (MKK) 1/2-extracellular signal
      regulated kinase (ERK) 1/2 signal pathway maintains the expression of Rad51.
      Therefore, in this study, we hypothesized that emodin could enhance the effects
      of the antitumor antibiotic mitomycin C (MMC)-mediated cytotoxicity by decreasing
      the expression of Rad51 and the phosphorylation of ERK1/2. Exposure of the human
      non-small-cell lung cancer H1703 or A549 cell lines to emodin decreased the MMC
      elicited phosphorylated ERK1/2 and Rad51 levels. Moreover, emodin significantly
      decreased the MMC-elicited Rad51 mRNA and protein levels by increasing the
      instability of Rad51 mRNA and protein. In emodin- and MMC-cotreated cells, ERK1/2
      phosphorylation was enhanced by constitutively active MKK1/2 (MKK1/2-CA), thus
      increasing Rad51 protein levels and protein stability. The synergistic cytotoxic
      effects induced by emodin combined with MMC were remarkably decreased by MKK1-CA
      mediated enhancement of ERK1/2 activation. Depletion of endogenous Rad51
      expression by small interfering Rad51 RNA transfection significantly enhanced MMC
      induced cell death and cell growth inhibition. In contrast, overexpression of
      Rad51 protects lung cancer cells from the synergistic cytotoxic effects induced
      by emodin and MMC. We conclude that suppression of Rad51 expression or a
      combination of emodin with chemotherapeutic agents may be considered as potential
      therapeutic modalities for lung cancer.

PMID- 20042516
TI  - High seroprevalence of neutralizing capacity against human metapneumovirus in all
      age groups studied in Bonn, Germany.
AB  - Human metapneumovirus (hMPV) infections occur frequently despite high rates of
      perpetual seroprevalence for all age groups. Analyses of approximately 2,000
      archived, randomly selected serum samples demonstrated that neutralizing
      capacities remain high, with a minor decrease for individuals over 69 years of
      age, leading to the hypothesis that reinfections occur because humoral immune
      responses play minor roles in the clearance of hMPV infections.

PMID- 20042517
TI  - Immunogenicity of a heptavalent conjugate pneumococcal vaccine administered
      concurrently with a combination diphtheria, tetanus, five-component acellular
      pertussis, inactivated polio, and Haemophilus influenzae type B vaccine and a
      meningococcal group C conjugate vaccine at 2, 3, and 4 months of age.
AB  - The immunogenicities of conjugate pneumococcal vaccines have been demonstrated
      when they are administered at 2, 3, and 4 months of age. There is a paucity of
      data on the immunogenicity of this vaccine when it is administered concurrently
      with other vaccines in the primary immunization schedule of the United Kingdom.
      We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent
      pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC)
      vaccine, and the diphtheria, tetanus, five-component acellular pertussis,
      inactivated polio, and Haemophilus influenzae type b (DTaP(5)/IPV/Hib-TT)
      vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus
      vaccines were measured at 2, 5, and 12 months of age; and the immune responses to
      PCV7 were measured at 2 and 5 months and then either at 12 months or following a
      4th dose of PCV7. There were increases in the geometric mean concentrations
      (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the
      infants achieved putatively protective levels postimmunization for all vaccine
      antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes
      increased following a 4th dose, although one infant had not reached putative
      levels of protection against serotype 6B. In conclusion, when infants were
      vaccinated according to the schedule described above, they had lower postprimary
      immunization responses to Hib, meningococcus group C capsular polysaccharide, and
      pneumococcal serotype 6B than the responses demonstrated by use of the other
      schedules. Despite this finding, there was a good response following a 4th dose
      of PCV7.

PMID- 20042518
TI  - Discrepancy in dengue virus neutralizing antibody titers between plaque reduction
      neutralizing tests with Fcgamma receptor (FcgammaR)-negative and FcgammaR
      expressing BHK-21 cells.
AB  - Protective immunity against dengue virus (DENV) is best reflected by the presence
      of neutralizing antibodies. The conventional plaque reduction neutralizing test
      (PRNT) is performed using Fcgamma receptor (FcgammaR)-negative cells. Because
      FcgammaR plays a key role in antibody-dependent enhancement, we examined
      neutralizing antibody titers of mouse monoclonal antibodies and human serum
      samples in PRNTs using FcgammaRIIA-negative and FcgammaRIIA-expressing BHK cells.
      There was a discrepancy in dengue virus neutralizing antibody titers between
      PRNTs using FcgammaRIIA-negative versus FcgammaRIIA-expressing BHK cells.
      Neutralizing antibody titers to DENV-1 and DENV-2 tested with monoclonal
      antibodies, and with most of the human serum samples, were higher in assays using
      BHK cells than those using FcgammaRIIA-expressing BHK cells. The results suggest
      that neutralizing antibody titers determined using FcgammaRIIA-expressing cells
      may better reflect the protective capacity of anti-DENV antibodies, as the major
      target cells of DENV infection are FcgammaR-positive cells.

PMID- 20042520
TI  - Evaluation of a rapid serological test for the determination of Mycobacterium
      bovis infection in badgers (Meles meles) found dead.
AB  - Between October 2005 and May 2006, a total of 727 badgers found dead in Wales
      were reported, and 550 were delivered to the Regional Laboratories of the
      Veterinary Laboratories Agency (VLA). Of the 459 carcasses suitable for
      examination, 55 were deemed to be infected with Mycobacterium bovis on the basis
      of culture, spoligotyping, and variable-number tandem repeat typing. Acid-fast
      bacteria were observed histologically in a further six badgers, but these
      bacteria were not confirmed as M. bovis by culture. A rapid serological test
      (BrockTB Stat-Pak) performed on thoracic blood showed a sensitivity of 35% and a
      specificity of 99%. Presence of M. bovis infection was 45 times more likely to be
      confirmed postmortem by culture in BrockTB Stat-Pak-reactive animals than in
      seronegative ones. Using visible carcass lesions as a marker of bovine
      tuberculosis (bTB) infection had a similar sensitivity (38%) but was
      significantly less specific (84%) than serology. The overall accuracy of the
      antibody detection was 93% (346 correct results from 374 tests), whereas the
      accuracy of regarding visible lesions as a marker for bTB infection was 78% (354
      correct from 453 carcasses examined). Culture remains the gold standard method
      for detecting M. bovis infection in badgers. However, where resources are limited
      and/or an instant result is preferred, the BrockTB Stat-Pak could be used in
      field surveillance efforts to identify animals which should be examined further
      by only submitting test-negative animals to more detailed postmortem examination
      and culture.

PMID- 20042519
TI  - Specific IgG responses to recombinant antigen B and em18 in cystic and alveolar
      echinococcosis in china.
AB  - An understanding of the correlation of the specific antibody responses and the
      disease phase is essential in evaluating diagnostic values of immunological tests
      in human echinococcosis. In this study, 422 echinococcosis patients diagnosed by
      ultrasonography, including 246 with cystic echinococcosis (CE), 173 with alveolar
      echinococcosis (AE), and 3 with dual infection, were tested for specific IgG in
      sera against recombinant AgB (rAgB) and recombinant Em18 (rEm18) in an enzyme
      linked immunosorbent assay. As a result, rAgB-specific antibody was detected in
      77.6% of CE and 86.1% of AE patients, while rEm18-specific antibody was present
      in 28.9% of CE and 87.3% of AE patients. Additionally, all three patients with
      dual infection exhibited specific antibodies responding to rAgB and rEm18.
      Further analysis revealed that rAgB-specific antibody was elevated in a
      significantly greater proportion (87.3%) of CE patients with cysts at active or
      transitional stages (CE1, CE2, or CE3), compared to 54.8% of other patients with
      cysts at an early or an inactive stage (CL or CE4 or CE5). Furthermore, rAgB
      specific antibody was detected in 95.6% of CE2 cases, which was statistically
      greater than that (73.7%) in CE1 patients. Although rEm18-specific antibody was
      elevated in 28.9% of CE patients, the positive reaction was much weaker in CE
      than in AE cases. Serum levels and concentrations of rEm18-specific antibody were
      further indicated to be strongly disease phase correlated in AE patients, with
      positive rates of 97.4% in cases with alveolar lesions containing central
      necrosis and 66.7% in patients with early alveolar lesions that measured </=5 cm.

PMID- 20042521
TI  - Genotypes coding for low serum levels of mannose-binding lectin are
      underrepresented among individuals suffering from noninfectious systemic
      inflammatory response syndrome.
AB  - Gene polymorphisms, giving rise to low serum levels of mannose-binding lectin
      (MBL) or MBL-associated protease 2 (MASP2), have been associated with an
      increased risk of infections. The objective of this study was to assess the
      outcome of intensive care unit (ICU) patients with systemic inflammatory response
      syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2
      gene polymorphisms. The study included 243 ICU patients with SIRS admitted to our
      hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single
      nucleotide polymorphisms were genotyped using a sequence-based typing technique.
      No differences were observed regarding the frequencies of low-MBL genotypes (O/O
      and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy
      controls. Interestingly, ICU patients with a noninfectious SIRS had a lower
      frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes
      (A/A and A/XA) than either ICU patients with an infectious SIRS or healthy
      controls. The existence of low- or /high-MBL genotypes or a MASP2 polymorphism
      had no impact on the mortality rates of the included patients. The presence of
      high-MBL-producing genotypes in patients with a noninfectious insult is a risk
      factor for SIRS and ICU admission.

PMID- 20042522
TI  - Diet-dependent acid load, Paleolithic [corrected] nutrition, and evolutionary
      health promotion.

PMID- 20042523
TI  - Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal
      cancer risk.
AB  - BACKGROUND: Isothiocyanates, compounds found primarily in cruciferous vegetables,
      have been shown in laboratory studies to possess anticarcinogenic activity.
      Glutathione S-transferases (GSTs) are involved in the metabolism and elimination
      of isothiocyanates; thus, genetic variations in these enzymes may affect in vivo
      bioavailability and the activity of isothiocyanates. OBJECTIVE: The objective was
      to prospectively evaluate the association between urinary isothiocyanate
      concentrations and colorectal cancer risk as well as the potential modifying
      effect of GST genotypes on the association. DESIGN: A nested case-control study
      of 322 cases and 1251 controls identified from the Shanghai Women's Health Study
      was conducted. RESULTS: Urinary isothiocyanate concentrations were inversely
      associated with colorectal cancer risk; the inverse association was statistically
      significant or nearly significant in the GSTM1-null (P for trend = 0.04) and the
      GSTT1-null (P for trend = 0.07) genotype groups. The strongest inverse
      association was found among individuals with both the GSTM1-null and the GSTT1
      null genotypes, with an adjusted odds ratio of 0.51 (95% CI: 0.27, 0.95), in a
      comparison of the highest with the lowest tertile of urinary isothiocyanates. No
      apparent associations between isothiocyanate concentration and colorectal cancer
      risk were found among individuals who carried either the GSTM1 or GSTT1 gene (P
      for interaction < 0.05). CONCLUSION: This study suggests that isothiocyanate
      exposure may reduce the risk of colorectal cancer, and this protective effect may
      be modified by the GSTM1 and GSTT1 genes.

PMID- 20042524
TI  - Effects of a low-salt diet on idiopathic hypercalciuria in calcium-oxalate stone
      formers: a 3-mo randomized controlled trial.
AB  - BACKGROUND: A direct relation exists between sodium and calcium excretion, but
      randomized studies evaluating the sustained effect of a low-salt diet on
      idiopathic hypercalciuria, one of the main risk factors for calcium-oxalate stone
      formation, are still lacking. OBJECTIVE: Our goal was to evaluate the effect of a
      low-salt diet on urinary calcium excretion in patients affected by idiopathic
      calcium nephrolithiasis. DESIGN: Patients affected by idiopathic calcium stone
      disease and hypercalciuria (>300 mg Ca/d in men and >250 mg Ca/d in women) were
      randomly assigned to receive either water therapy alone (control diet) or water
      therapy and a low-salt diet (low-sodium diet) for 3 mo. Twenty-four-hour urine
      samples were obtained twice from all patients: one sample at baseline on a free
      diet and one sample after 3 mo of treatment. RESULTS: A total of 210 patients
      were randomly assigned to receive a control diet (n = 102) or a low-sodium diet
      (n = 108); 13 patients (2 on the control diet, 11 on the low-sodium diet)
      withdrew from the trial. At the follow-up visit, patients on the low-sodium diet
      had lower urinary sodium (mean +/- SD: 68 +/- 43 mmol/d at 3 mo compared with 228
      +/- 57 mmol/d at baseline; P < 0.001). Concomitant with this change, they showed
      lower urinary calcium (271 +/- 86 mg/d at 3 mo compared with 361 +/- 129 mg/d on
      the control diet, P < 0.001) and lower oxalate excretion (28 +/- 8 mg/d at 3 mo
      compared with 32 +/- 10 mg/d on the control diet, P = 0.001). Urinary calcium was
      within the normal range in 61.9% of the patients on the low-salt diet and in
      34.0% of those on the control diet (difference: +27.9%; 95% CI: +14.4%, +41.3%; P
      < 0.001). CONCLUSION: A low-salt diet can reduce calcium excretion in
      hypercalciuric stone formers. This trial was registered at clinicaltrials.gov as
      NCT01005082.

PMID- 20042526
TI  - Emerging opportunities for monitoring the nutritional content of processed foods.

PMID- 20042525
TI  - Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.
AB  - BACKGROUND: Processed meat and fish have been shown to be associated with the
      risk of advanced prostate cancer, but few studies have examined diet after
      prostate cancer diagnosis and risk of its progression. OBJECTIVE: We examined the
      association between postdiagnostic consumption of processed and unprocessed red
      meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or
      progression. DESIGN: We conducted a prospective study in 1294 men with prostate
      cancer, without recurrence or progression as of 2004-2005, who were participating
      in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were
      followed for an average of 2 y. RESULTS: We observed 127 events (prostate cancer
      death or metastases, elevated prostate-specific antigen concentration, or
      secondary treatment) during 2610 person-years. Intakes of processed and
      unprocessed red meat, fish, total poultry, and skinless poultry were not
      associated with prostate cancer recurrence or progression. Greater consumption of
      eggs and poultry with skin was associated with 2-fold increases in risk in a
      comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10,
      3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P
      for trend = 0.003). An interaction was observed between prognostic risk at
      diagnosis and poultry. Men with high prognostic risk and a high poultry intake
      had a 4-fold increased risk of recurrence or progression compared with men with
      low/intermediate prognostic risk and a low poultry intake (P for interaction =
      0.003). CONCLUSIONS: Our results suggest that the postdiagnostic consumption of
      processed or unprocessed red meat, fish, or skinless poultry is not associated
      with prostate cancer recurrence or progression, whereas consumption of eggs and
      poultry with skin may increase the risk.

PMID- 20042527
TI  - Estimation of the diet-dependent net acid load in 229 worldwide historically
      studied hunter-gatherer societies.
AB  - BACKGROUND: Nutrition scientists are showing growing interest in the diet
      patterns of preagricultural (hunter-gatherer) humans. Retrojected preagricultural
      diets are reportedly predominantly net base producing in contrast to the net acid
      producing modern Western diets. OBJECTIVE: We examined the dietary net acid load
      [net endogenous acid production (NEAP)] for 229 worldwide historically studied
      hunter-gatherer societies to determine how differences in plant-to-animal (P:A)
      dietary subsistence patterns and differences in the percentage of body fat in
      prey animals affect the NEAP. DESIGN: With the use of 1) ethnographic data of
      dietary P:A ratios of hunter-gatherer populations, 2) established computational
      methods, and 3) knowledge that fat densities of animal foods consumed by hunter
      gatherers varied between 3% and 20%, we computed the NEAP for the diets of 229
      populations in 4 different models of animal fat densities (model A, 3%; model B,
      10%; model C, 15%; model D, 20%). RESULTS: As P:A ratios decreased from 85:15 to
      5:95, the NEAP increased from -178 to +181 mEq/d (model A) and from -185 to +120
      mEq/d (models B and C). Approximately 50% of the diets consumed by the 229
      worldwide hunter-gatherer populations were net acid producing (models B and C).
      In model D, 40% of the diets were net acid producing. CONCLUSIONS: Our data
      confirm that the NEAP of hunter-gatherer diets becomes progressively more
      positive as P:A ratios decline. The high reliance on animal-based foods of a
      worldwide sample of historically studied hunter-gatherer populations renders
      their diets net acid producing in approximately 40-60% of subgroups of P:A
      ratios. Only further investigations can show the implications of these findings
      in determining the NEAP of human ancestral diets.

PMID- 20042528
TI  - Effects of price discounts and tailored nutrition education on supermarket
      purchases: a randomized controlled trial.
AB  - BACKGROUND: Traditional methods to improve population diets have largely relied
      on individual responsibility, but there is growing interest in structural
      interventions such as pricing policies. OBJECTIVE: The aim was to evaluate the
      effect of price discounts and tailored nutrition education on supermarket food
      and nutrient purchases. DESIGN: A 2 x 2 factorial randomized controlled trial was
      conducted in 8 New Zealand supermarkets. A total of 1104 shoppers were randomly
      assigned to 1 of the following 4 interventions that were delivered over 6 mo:
      price discounts (12.5%) on healthier foods, tailored nutrition education,
      discounts plus education, or control (no intervention). The primary outcome was
      change in saturated fat purchased at 6 mo. Secondary outcomes were changes in
      other nutrients and foods purchased at 6 and 12 mo. Outcomes were assessed by
      using electronic scanner sales data. RESULTS: At 6 mo, the difference in
      saturated fat purchased for price discounts on healthier foods compared with that
      purchased for no discount on healthier foods was -0.02% (95% CI: -0.40%, 0.36%; P
      = 0.91). The corresponding difference for tailored nutrition education compared
      with that for no education was -0.09% (95% CI: -0.47%, 0.30%; P = 0.66). However,
      those subjects who were randomly assigned to receive price discounts bought
      significantly more predefined healthier foods at 6 mo (11% more; mean difference:
      0.79 kg/wk; 95% CI: 0.43, 1.16; P < 0.001) and 12 mo (5% more; mean difference:
      0.38 kg/wk; 95% CI: 0.01, 0.76; P = 0.045). Education had no effect on food
      purchases. CONCLUSIONS: Neither price discounts nor tailored nutrition education
      had a significant effect on nutrients purchased. However, the significant and
      sustained effect of discounts on food purchases suggests that pricing strategies
      hold promise as a means to improve population diets.

PMID- 20042529
TI  - Estrogen treatment blocks 8-hydroxy-2-dipropylaminotetralin- and apomorphine
      induced disruptions of prepulse inhibition: involvement of dopamine D1 or D2 or
      serotonin 5-HT1A, 5-HT2A, or 5-HT7 receptors.
AB  - Prepulse inhibition (PPI) is a measure of sensorimotor gating and an
      endophenotype of schizophrenia. We have shown previously in rats that estrogen
      treatment prevents disruption of PPI by the 5-HT(1A)/5-HT(7) receptor agonist 8
      hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The aim of the present study was to
      examine the role of dopamine D(1) and D(2) and serotonin 5-HT(1A), 5-HT(2A), and
      5-HT(7) receptors in these effects. Part 1 of this study investigated the ability
      of estrogen treatment to reverse PPI disruption induced by 8-OH-DPAT or the
      dopamine D(1)/D(2) receptor agonist apomorphine. Part 2 of this study compared
      these effects to the ability of various antagonists in reversing the action of 8
      OH-DPAT and apomorphine on PPI. Female Sprague-Dawley rats were ovariectomized
      (OVX), and, where appropriate, they received silastic implants containing either
      a low (E20) or high dose (E100) of estrogen. Two weeks later, PPI was assessed
      using automated startle boxes. The disruption of PPI by either treatment with 8
      OH-DPAT (0.5 mg/kg) or apomorphine (0.3 mg/kg) was similarly prevented by E100
      treatment. 8-OH-DPAT-induced PPI disruption was reversed by pretreatment with the
      5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2
      pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg) and the
      typical antipsychotic and dopamine D(2) receptor antagonist haloperidol (0.25
      mg/kg), but it was not reversed by pretreatment with the dopamine D(1) receptor
      antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3
      benzazepine hydrochloride (SCH 23390; 0.1 mg/kg), the 5-HT(2A/2C) receptor
      antagonist ketanserin (2 mg/kg), or the 5-HT(7) receptor antagonist SB-269970 (10
      mg/kg). Apomorphine-induced disruptions of PPI were reversed by haloperidol and
      SCH 23390 only. Estrogen may prevent disruptions of PPI induced by both 8-OH-DPAT
      and apomorphine by an action on dopamine D(2) receptors downstream of 5-HT(1A)
      receptors.

PMID- 20042530
TI  - Pathogenic importance of cysteinyl leukotrienes in development of gastric lesions
      induced by ischemia/reperfusion in mice.
AB  - We examined the role of cysteinyl leukotrienes (CysLTs) in the gastric
      ulcerogenic response to ischemia/reperfusion (I/R) in mice. Experiments were
      performed in male C57BL/6J mice after 18-h fasting. Under urethane anesthesia,
      the celiac artery was clamped for 30 min, and then reperfusion was achieved by
      removing the clamp. The stomach was examined for lesions 60 min thereafter. The
      severity of I/R-induced gastric damage was reduced by prior administration of
      pranlukast [CysLT receptor type 1 (CysLT(1)R) antagonist] as well as 1-[[5'-(3''
      methoxy-4''-ethoxycarbonyl-oxyphenyl)-2',4'-pentadienoyl]aminoethyl]-4
      diphenylmethoxypiperidine [TMK688; 5-lipoxygenase (5-LOX) inhibitor]. On the
      contrary, these lesions were markedly worsened by pretreatment with indomethacin,
      and this response was abrogated by the coadministration of TMK688 or pranlukast.
      The gene expression of CysLT(1)R but not 5-LOX was up-regulated in the stomach
      after I/R, but both expressions were increased under I/R in the presence of
      indomethacin. I/R slightly increased the mucosal CysLT content of the stomach,
      yet this increase was markedly enhanced when the animals were pretreated with
      indomethacin. The increased CysLT biosynthetic response to indomethacin during
      I/R was attenuated by TMK688. Indomethacin alone caused a slight increase of
      CysLT(1)R expression and markedly up-regulated 5-LOX expression in the stomach.
      We concluded that I/R up-regulated the expression of CysLT(1)R in the stomach;
      CysLTs play a role in the pathogenesis of I/R-induced gastric damage through the
      activation of CysLT(1)R; and the aggravation by indomethacin of these lesions may
      be brought about by the increase of CysLT production and the up-regulation of 5
      LOX expression, in addition to the decreased prostaglandin production.

PMID- 20042531
TI  - Performance of mouse neural stem cells as a screening reagent: characterization
      of PAC1 activity in medium-throughput functional assays.
AB  - The self-renewal and phenotypic properties of neural stem cells make them an
      abundant and more physiologically relevant alternative to recombinant cell lines
      for drug screens to identify ligands acting at neural targets. Here, the authors
      use high-throughput phenotypic and signaling assays to test the ability of neural
      stem cells isolated from postnatal mouse hippocampus (mNSCs) to deliver high
      content and physiologically relevant data on native peptide receptor activity.
      The authors find that mNSCs express PAC1 but not the related VPAC1 and VPAC2
      receptors. PAC1 promotes both the proliferation of mNSCs and their
      differentiation into neuronal-like cells. In addition, the authors show that PAC1
      stimulates markedly different extracellular signal-regulated kinase signals in
      mNSCs than in recombinant CHO-PAC1 cells and is able to couple to Ca(2+)
      elevation only in CHO-PAC1 cells. These data suggest that G-protein coupling in
      CHO-PAC1 cells is nonphysiological, which may affect the ligand binding
      properties of the receptor and thus distort the results of a screen by increasing
      numbers of false positives/negatives. This work reinforces the emerging
      pharmacological theory that recombinant cell lines are often inappropriate models
      of natively expressing primary cells, and the authors conclude that mNSCs are a
      viable and relevant physiological alternative for use in high-throughput drug
      screens.

PMID- 20042532
TI  - Colloid chitin azure is a dispersible, low-cost substrate for chitinase
      measurements in a sensitive, fast, reproducible assay.
AB  - Chitin and its derivatives are widely used as biomedical materials because of
      their versatility and biocompatibility. Chitinases are enzymes that produce chito
      oligosaccharides from chitin. The assay of chitinase activity is difficult
      because few appropriate substrates are available. In this study, the authors
      developed an efficient and low-cost chitinase assay using colloidal chitin azure.
      The assay feasibility is evaluated and compared with traditional assays employing
      colloidal chitin and chitin azure. The authors found that the optimum pH for
      determining chitinase activity using colloid chitin azure was pH 5 or 8. The
      method was sensitive, and the assay was complete within 30 min. When the assay
      was used to measure chitinase activities produced by 2 strains of chitinolytic
      bacteria, BCTS (an Escherichia coli BL21 [DE3] expressing a secretory recombinant
      chitinase) and AS1 (a chitinolytic bacterium with low levels of chitinase), it
      was shown that cultivation in Bushnell-Haas selection medium caused AS1 to
      secrete a higher level of chitinase than was secreted when the bacterium grew in
      other media. In summary, colloid chitin azure is a sensitive, feasible,
      reproducible, and low-cost substrate for the assay of chitinase activity.

PMID- 20042533
TI  - Measuring acceptability of clinical decision rules: validation of the Ottawa
      acceptability of decision rules instrument (OADRI) in four countries.
AB  - BACKGROUND: Clinical decision rules can benefit clinicians, patients, and health
      systems, but they involve considerable up-front development costs and must be
      acceptable to the target audience. No existing instrument measures the
      acceptability of a rule. The current study validated such an instrument. METHODS:
      The authors administered the Ottawa Acceptability of Decision Rules Instrument
      (OADRI) via postal survey to emergency physicians from 4 regions (Australasia,
      Canada, United Kingdom, and United States), in the context of 2 recently
      developed rules, the Canadian C-Spine Rule (C-Spine) and the Canadian CT Head
      Rule (CT-Head). Construct validity of the 12-item instrument was evaluated by
      hypothesis testing. RESULTS: As predicted by a priori hypotheses, OADRI scores
      were 1) higher among rule users than nonusers, 2) higher among those using the
      rule ''all of the time'' v. ''most of the time'' v. ''some of the time,'' and 3)
      higher among rule nonusers who would consider using a rule v. those who would
      not. We also examined explicit reasons given by respondents who said they would
      not use these rules. Items in the OADRI accounted for 85.5% (C- Spine) and 90.2%
      (CT-Head) of the reasons given for not considering a rule acceptable.
      CONCLUSIONS: The OADRI is a simple, 12-item instrument that evaluates rule
      acceptability among clinicians. Potential uses include comparing multiple
      ''protorules'' during development, examining acceptability of a rule to a new
      audience prior to implementation, indicating barriers to rule use addressable by
      knowledge translation interventions, and potentially serving as a proxy measure
      for future rule use.

PMID- 20042534
TI  - Life expectancy in individuals with type 2 diabetes: implications for annuities.
AB  - BACKGROUND: Insurance companies often offer people with diabetes ''enhanced
      impaired life annuity'' at preferential rates, in view of their reduced life
      expectancy. OBJECTIVE: To assess the appropriateness of ''enhanced impaired life
      annuity'' rates for individuals with type 2 diabetes. Patients. There were 4026
      subjects with established type 2 diabetes (but not known cardiovascular or other
      life-threatening diseases) enrolled into the UK Lipids in Diabetes Study.
      Measurements. Estimated individual life expectancy using the United Kingdom
      Prospective Diabetes Study (UKPDS) Outcomes Model. RESULTS: Subjects were a mean
      (SD) age of 60.7 (8.6) years, had a blood pressure of 141/83 (17/10) mm Hg, total
      cholesterol level of 4.5 (0.75) mmol/L, HDL cholesterol level of 1.2 (0.29)
      mmol/L, with median (interquartile range [IQR]) known diabetes duration of 6 (3
      11) years, and HbA(1c) of 8.0% (7.2-9.0). Sixty-five percent were male, 91%
      white, 4% Afro-Caribbean, 5% Indian-Asian, and 15% current smokers. The UKPDS
      Outcomes Model median (IQR) estimated age at death was 76.6 (73.8-79.5) years
      compared with 81.6 (79.4-83.2) years, estimated using the UK Government Actuary's
      Department data for a general population of the same age and gender structure.
      The median (IQR) difference was 4.3 (2.8-6.1) years, a remaining life expectancy
      reduction of almost one quarter. The highest value annuity identified, which
      commences payments immediately for a 60-year-old man with insulin-treated type 2
      diabetes investing 100,000, did not reflect this difference, offering 7.4K per
      year compared with 7.0K per year if not diabetic. CONCLUSIONS: The UK Government
      Actuary's Department data overestimate likely age at death in individuals with
      type 2 diabetes, and at present, ''enhanced impaired life annuity'' rates do not
      provide equity for people with type 2 diabetes. Using a diabetes-specific model
      to estimate life expectancy could provide valuable information to the annuity
      industry and permit more equitable annuity rates for those with type 2 diabetes.

PMID- 20042535
TI  - Controlled ovarian hyperstimulation for in vitro fertilization alters endometrial
      receptivity in humans: protocol effects.
AB  - The impact of gonadotropin-releasing hormone (GnRH) agonist long compared with
      GnRH antagonist protocols, under in vitro fertilization conditions on endometrial
      receptivity, is still debated. Therefore, we compared the effect of both GnRH
      antagonist and agonist long protocols on the endometrial receptivity by
      analyzing, to our knowledge for the first time, the global gene expression
      profile shift during the prereceptive and receptive stages of stimulated cycles
      under the two GnRH analogue protocols compared with natural cycles in the same
      patients. For the same normal-responder patients, endometrial biopsies were
      collected on the day of oocyte retrieval and on the day of embryo transfer after
      human chorionic gonadotropin administration of a stimulated cycle with either
      GnRH agonist long or GnRH antagonist protocols and compared with the prereceptive
      and receptive stages of a natural cycle. Samples were analyzed using DNA
      microarrays. Gene expression profiles and biological pathways involved during the
      prereceptive stage to the receptive endometrial transition of stimulated and
      natural cycles were analyzed and compared for each patient. Both protocols affect
      endometrial receptivity in comparison with their natural cycle in the same
      patients. Major differences in endometrial chemokines and growth factors under
      stimulated cycles in comparison with natural cycles were observed. Such an effect
      has been associated with gene expression alterations of endometrial receptivity.
      However, the endometrial receptivity under the GnRH antagonist protocol was more
      similar to the natural cycle receptivity than that under the GnRH agonist
      protocol.

PMID- 20042536
TI  - Functional deficiencies and a reduced response to calcium in the flagellum of
      mouse sperm lacking SPAG16L.
AB  - The Spag16L gene codes for a protein that is localized to the central apparatus
      which is essential for normal sperm motility and male fertility. Sperm from mice
      homozygous for a targeted deletion of the Spag16L gene were examined to assess
      their flagellar motor functions compared with age- and strain-matched control
      sperm. Sperm were also demembranated with Triton X-100 and examined for their
      ability to respond to free calcium, as well as for their ability to undergo
      microtubule sliding driven by dynein action. In addition, the passive flagella,
      inhibited by sodium metavanadate to disable the dyneins, were examined for
      mechanical abnormalities. Live Spag16L-null sperm exhibited much less bending of
      the flagellum during the beat. The amount of microtubule sliding in the R-bend
      direction of the beat was selectively restricted, which suggests that there is
      limited activation of the dyneins on one side of the axoneme in the live cells.
      This is corroborated by the results on detergent-extracted sperm models. The
      flagellar response to calcium is greatly reduced. The calcium response requires
      the activation of the dyneins on outer doublets 1, 2, 3, and 4. These are the
      same dyneins required for R-bend formation. In axonemes prepared to disintegrate
      by microtubule sliding, we observed little or no extrusion of doublets 1 and 2,
      consistent with a reduced activity of their dyneins. This deficit in motor
      function, and an increased rigidity of the midpiece region which we detected in
      the passive flagella, together can explain the observed motility characteristics
      of the Spag16L-null sperm.

PMID- 20042537
TI  - Uterine vein infusion of interferon tau (IFNT) extends luteal life span in ewes.
AB  - Interferon tau (IFNT) from the ovine conceptus has paracrine actions on the
      endometrium that alter release of prostaglandin F(2alpha) (PGF) and protect the
      corpus luteum (CL). Antiviral activity in uterine vein blood and expression of
      interferon-stimulated genes (ISGs) in CL is greater in pregnant than in
      nonpregnant ewes. We hypothesized that IFNT contributes to antiviral activity in
      uterine vein blood and has endocrine actions on the CL. Preadsorption of IFNT
      with antiserum against recombinant ovine (ro) IFNT revealed that antiviral
      activity in uterine vein blood from pregnant ewes was mediated by IFNT. Endocrine
      actions of IFNT were examined after infusing either roIFNT or bovine serum
      albumin (BSA; 200 microg/24 h; mini-osmotic pump) into the uterine vein of
      nonpregnant ewes from Day 10 to Day 11 postestrus. The abundance of ISG15 mRNA
      and protein was greater in CL (P < 0.05) from ewes receiving 24-h roIFNT infusion
      compared to that from ewes receiving 24-h BSA infusion. Injection of PGF at 12 h
      following insertion of mini-osmotic pumps resulted in a decline in serum
      progesterone concentrations 6 through 12 h later in BSA-infused ewes; however, in
      roIFNT-infused ewes, a similar decline in progesterone concentrations at 6 h was
      followed by recovery to control values at 12 h. Ewes then received infusions (200
      microg/day) of either roIFNT or BSA for 7 days beginning on Day 10 of the estrous
      cycle. All BSA-infused ewes returned to estrus by Day 19, whereas 80% of roIFNT
      infused ewes maintained luteal-phase concentrations of progesterone through Day
      32. In conclusion, IFNT is released from the uterus into the uterine vein and
      acts through an endocrine mechanism to induce ISGs in the CL and delay
      luteolysis.

PMID- 20042540
TI  - 'A life or death decision' for pollen tubes in S-RNase-based self
      incompatibility.
AB  - Mate choice is an essential process during sexual plant reproduction, in which
      self-incompatibility (SI) is widely adopted as an intraspecific reproductive
      barrier to inhibit self-fertilization by many flowering plants. Genetic studies
      show that a single polymorphic S-locus, encoding at least two components from
      both the pollen and pistil sides, controls the discrimination of self and non
      self pollen. In the Solanaceae, Plantaginaceae, and Rosaceae, an S-RNase-based SI
      mechanism is involved in such a discrimination process. Recent studies have
      provided some important clues to how a decision is made to accept cross pollen or
      specifically to reject self pollen. In this review, the molecular features of the
      pistil and pollen S-specificity factors are briefly summarized and then our
      current knowledge of the molecular control of cross-pollen compatibility (CPC)
      and self-pollen incompatibility (SPI) responses, respectively, is presented. The
      possible biochemical mechanisms of the specificity determinant between the pistil
      and pollen S factors are discussed and a hypothetical S-RNase endosome sorting
      model is proposed to illustrate the distinct destinies of pollen tubes following
      compatible and incompatible pollination.

PMID- 20042538
TI  - The annulus of the mouse sperm tail is required to establish a membrane diffusion
      barrier that is engaged during the late steps of spermiogenesis.
AB  - The annulus is a higher order septin cytoskeletal structure located between the
      midpiece and principal piece regions of the sperm tail. The annulus has been
      hypothesized to generate the diffusion barrier that exists between these two
      membrane domains. We tested this premise directly on septin 4 knockout mice,
      whose sperm are viable but lack an annulus, by following the diffusing membrane
      protein basigin. Basigin is normally confined to the principal piece domain on
      testicular and caput sperm, but undergoes relocation into the midpiece during
      sperm epididymal transit. On Sept4(-/-) sperm, domain confinement was lost, and
      basigin localized over the entire plasma membrane. Both immunofluorescence and
      immunoblotting further revealed reduced levels of basigin expression on sperm
      from the knockout. Testicular immunohistochemistry showed similar basigin
      expression and tail targeting in wild-type (WT) and Sept4(-/-) tubules until step
      15 of spermatid development, at which point basigin was redistributed throughout
      the plasma membrane of Sept4(-/-) spermatids. The basigin outside of the tail was
      subsequently lost around the time of sperm release into the lumen. The
      redistribution in the knockout coincides with the time in WT sperm when the
      annulus completes its migration from the neck down to the midpiece-principal
      piece junction. We posit that basigin may not diffuse freely until after the
      annulus arrives at the midpiece-principal piece junction to restrict lateral
      movement. These results are the strongest evidence to date of a mammalian septin
      structure establishing a membrane diffusion barrier.

PMID- 20042539
TI  - A pair of mouse KRAB zinc finger proteins modulates multiple indicators of female
      reproduction.
AB  - Kruppel-associated box-zinc finger proteins (KRAB-ZFPs) are the largest class of
      transcriptional regulators in mammals, yet few have been assigned biological
      roles. Cloning the genes underlying the regulator of sex-limitation (rsl)
      phenotype, in which the normally male-specific sex-limited protein (SLP) is
      expressed in female mice, identified two KRAB-ZFPs, Rsl1 and Rsl2, as influencing
      sexually dimorphic liver gene expression. Combined absence of both repressors in
      rsl mice leads to increased expression in female liver of major urinary proteins
      (MUPs) and certain enzymes of steroid metabolism, as well as SLP. We hypothesized
      that this altered gene expression might affect reproductive physiology in rsl
      females. Urinary MUP (uMUP) concentration varied with the estrous cycle in both
      wt and rsl females but was consistently higher in rsl urine. A behavioral odor
      test revealed that wild-type (wt) males preferred rsl to wt females, possibly due
      to elevated uMUPs providing greater pheromone presentation. To ascribe activity
      to Rsl1, Rsl2, or both, the genes were individually expressed as liver-specific
      transgenes. RSL2 overexpression accentuated uMUP fluctuations across the estrous
      cycle, whereas RSL1 overexpression did not. In addition, puberty onset, as
      indicated by vaginal opening (VO), occurred 2 days earlier in rsl females, and
      excess RSL2, but not RSL1, restored VO timing to wt. Hence, transcriptional
      repression by RSL in liver modifies female mouse reproduction via targets that
      likely impact both hormonal and pheromonal cues. The large and rapidly
      diversifying KRAB-ZFP family may modulate biological processes, including
      reproduction, to confer individual differences that may isolate populations and
      ultimately lead to speciation.

PMID- 20042541
TI  - Exposure to sexist humor and rape proclivity: the moderator effect of
      aversiveness ratings.
AB  - The aim of this study is to explore the effect of exposure to sexist humor about
      women on men's self-reported rape proclivity. Earlier studies have shown that
      exposure to this type of humor increases rape proclivity and that funniness
      responses to jokes are a key element to consider. However, the role of
      aversiveness responses has not been studied. In a between-group design, 109 male
      university students are randomly exposed to sexist or nonsexist jokes.
      Participants are asked to rate the jokes according to their degree of funniness
      and aversiveness. Participants' levels of hostile and benevolent sexism were also
      measured. Results about the relationship between sexist attitudes and sexist
      humor and the relationship between sexist attitudes and rape proclivity are
      consistent with those of earlier studies. However, exposure to sexist humor
      affects rape proclivity only when aversiveness shown to this type of humor is
      low. The results are discussed in the light of the prejudiced norm theory.

PMID- 20042542
TI  - School violence in Taiwan: examining how Western risk factors predict school
      violence in an Asian culture.
AB  - The current study explores whether theorized risk factors in Western countries
      can be used to predict school violence perpetration in an Asian cultural context.
      The study examines the associations between risk factors and school violence
      perpetration in Taiwan. Data were obtained from a nationally representative
      sample of 14,022 students from elementary to high school (Grades 4 to 12) across
      Taiwan. The analysis reported in this study focuses on only junior high school
      students (Grades 7 to 9, N = 3,058). The results of a regression analysis show
      that gender, age, direct victimization, witness victimization, alcohol use,
      smoking, anger traits, lack of impulse control, attitudes toward violence, poor
      quality of student-teacher relationships, and involvement with at-risk peers were
      significantly associated with school violence in Taiwan. The overall results
      suggest strong similarities in risk factors found in the West and school violence
      in Taiwan. They therefore point toward using similar strategies developed in the
      West to enhance students' positive experiences in their personal, family, and
      school lives to decrease school violence.

PMID- 20042543
TI  - Does inhibition of apolipoprotein B synthesis produce foie gras?

PMID- 20042544
TI  - Occurrence risk and structure of depression in Parkinson disease with and without
      dementia: results from the GEPAD Study.
AB  - BACKGROUND: This study examined the age- and gender-specific risk of depression
      in demented and non-demented participants, its symptom structure, and associated
      clinical factors in a nationwide random sample of n = 1449 outpatients with
      Parkinson disease (PD). METHODS: Depression ratings were based on a cross
      sectional clinical assessment including the clinical Montgomery-Asberg Depression
      Rating Scale (MADRS > or = 14). Parkinson disease severity was rated according to
      Hoehn and Yahr (HY) and the Unified Parkinson's Disease Rating Scale. Diagnosis
      of dementia was based on Diagnostic and Statistical Manual of Mental Disorders
      (Fourth Edition; DSM-IV) criteria. RESULTS: 25.2% (CI: 22.8-27.5) of all patients
      met study criteria for depression. Additionally, 8.4% of patients did not exceed
      the MADRS cut-off but were currently being treated with antidepressants, possibly
      suggesting a corrected (upper limit) total prevalence of 33.6%. Females were more
      likely depressive than males (29.3% vs 22.4%). In both genders, depression risk
      was elevated 2- to 4-fold depending on HY stage. Overall, highest rates in non
      demented patients were found in females at stages IV to V (53.7%, CI: 37.7-69.6).
      Demented patients were more likely to meet depression criteria than non-demented
      (up to 76.2%, 95% CI: 60.5-87.9). Depression symptom profiles for demented PD
      patients (as compared to non-demented) revealed no structural differences but
      consistently higher symptom scores. Neither age at onset of PD nor duration of
      disease were significantly linked with depression. CONCLUSIONS: Depression rates
      are already substantially elevated at early PD stages, emphasizing the need for a
      thorough examination of mood disorders in all patients with PD. Depression is
      associated with PD severity and dementia but not with age, age at onset of PD, or
      disease duration. The differential associations with dementia and the statistical
      independence of dementia and depression also suggest that depression could not be
      regarded as a mere demoralisation syndrome.

PMID- 20042545
TI  - Reports of neuropsychiatric symptoms of older care recipients by their family
      members and their foreign home care workers: results from triadic data.
AB  - OBJECTIVES: To evaluate reports of neuropsychiatric symptoms (NPS) per family
      members and round the clock foreign home care workers. DESIGN, SETTING, AND
      PARTICIPANTS: A cross-sectional matched sample of family members, foreign home
      care workers, and care recipients. MEASUREMENTS: Family members and foreign home
      care workers completed a measure of NPS. All 3 stakeholders provided a variety of
      demographic and clinical characteristics. RESULTS: There was a low agreement
      between family members and foreign home care workers with regard to reports of
      depression and disturbing behaviors in care recipient and a good agreement with
      regard to reports of memory problems. In addition to care recipients'
      characteristics, family members' characteristics were primarily correlated with
      family members' reports of NPS and foreign home care workers' characteristics
      were primarily associated with foreign home care workers' reports of NPS.
      CONCLUSIONS: Because much of the evaluation of NPS relies on reports of formal
      (ie, paid) and informal caregivers (ie, unpaid), clinicians should be aware of
      the fact that these reports are based in large part on the subjective perception
      of the caregiver.

PMID- 20042546
TI  - Focal cartilage defects in the knee impair quality of life as much as severe
      osteoarthritis: a comparison of knee injury and osteoarthritis outcome score in 4
      patient categories scheduled for knee surgery.
AB  - BACKGROUND: Patients with focal cartilage defects in the knee may suffer from
      both pain and functional impairment. Treatment options are often insufficient. It
      is not known, however, to what extent their complaints affect quality of life,
      compared with other knee disorders. Knee Injury and Osteoarthritis Outcome Score
      (KOOS) is a validated global knee score suitable for comparison of patients with
      knee complaints attributable to different causes. Hypothesis Complaints because
      of localized cartilage defects in the knee reduce quality of life measured by
      KOOS to a different extent than those due to anterior cruciate ligament
      deficiency and osteoarthritis, when comparing patients within the working
      population scheduled for surgery. STUDY DESIGN: Cross-sectional study; Level of
      evidence, 3. Methods Previously registered KOOS baseline data on patients
      enrolled in different knee treatment studies were included in the present study;
      the patients were 18 to 67 years of age (working population) at data
      registration. The different patient categories were (1) patients with knee
      osteoarthritis enrolled for knee arthroplasty, (2) patients with knee
      osteoarthritis enrolled for osteotomies around the knee, (3) patients with focal
      cartilage lesions enrolled for cartilage repair, and (4) patients with anterior
      cruciate ligament-deficient knees enrolled for anterior cruciate ligament
      reconstruction. The KOOS subscale quality of life was the main parameter for
      comparison of complaints. RESULTS: At preoperative baseline, patients with focal
      cartilage defects in the knee scored 27.5 on the KOOS subscale quality of life,
      not significantly different from the 28.8 and 27.2 in the patients with
      osteoarthritis enrolled for knee osteotomies and arthroplasties, respectively.
      For all the subscales of KOOS, the cartilage patients scored significantly lower
      than the patients with anterior cruciate ligament deficiency. CONCLUSION:
      Patients with focal cartilage lesions have major problems with pain and
      functional impairment. Their complaints are worse than those of patients with
      anterior cruciate ligament-deficient knees, and quality of life is affected to
      the same extent as in patients scheduled for knee replacement.

PMID- 20042547
TI  - Analysis of the static function of the popliteus tendon and evaluation of an
      anatomic reconstruction: the "fifth ligament" of the knee.
AB  - BACKGROUND: The popliteus tendon has important dynamic and static stabilizing
      functions at the knee. Evaluation of its static role as the "fifth ligament" of
      the knee and a subsequent analysis of a popliteus tendon reconstruction has not
      been performed. HYPOTHESIS: In vitro knee stability can be restored to a
      popliteus tendon-deficient knee with an anatomic popliteus tendon reconstruction.
      STUDY DESIGN: Controlled laboratory study. METHODS: Eleven nonpaired cadaveric
      knees were tested under the following popliteus tendon states: intact, sectioned,
      and reconstructed using an autogenous semitendinosus graft. Each knee was
      subjected to 10-N.m varus moments, 5-N.m external and internal torques, and 88-N
      anterior and posterior loads at flexion angles of 0 degrees , 20 degrees , 30
      degrees , 60 degrees , and 90 degrees . A 6 degrees of freedom electromagnetic
      motion tracking system was used to assess motion changes of the tibia with
      respect to the femur. RESULTS: Significant increases in external rotation and
      small but significant increases in internal rotation, varus angulation, and
      anterior translation motion were found after sectioning the popliteus tendon
      compared to the intact state. Significant decreases in external rotation were
      found in the reconstructed state compared with the sectioned state at knee
      flexion angles of 20 degrees , 30 degrees , 60 degrees , and 90 degrees .
      Comparing the reconstructed state to the intact state, there were no significant
      differences at knee flexion angles of 0 degrees and 20 degrees , but significant
      decreases of external rotation were found at knee flexion angles of 30 degrees ,
      60 degrees , and 90 degrees . Additionally, there were small but significant
      differences between the reconstructed and intact state with respect to varus
      angulation at knee flexion angles of 20 degrees , 30 degrees , and 60 degrees ;
      anterior translation at 20 degrees and 30 degrees ; and internal rotation at all
      flexion angles. CONCLUSION: The popliteus tendon has important primary
      stabilization roles at the knee. The authors also found that an anatomic
      popliteus tendon reconstruction significantly reduced the increase in external
      rotation that occurred with sectioning the popliteus tendon; however, differences
      seen with respect to internal rotation, varus angulation, and anterior
      translation were not restored. CLINICAL SIGNIFICANCE: The popliteus tendon
      functions essentially as the fifth major ligament of the knee. An anatomic
      popliteus tendon reconstruction can restore external rotation stability to knees
      with popliteus tendon injury.

PMID- 20042548
TI  - Genetic parameters for intramuscular fatty acid composition and metabolism in
      pigs.
AB  - The aim of this study was to estimate genetic parameters for pork intramuscular
      fatty acid (FA) composition and indices for desaturase and elongase activities
      involved in n-3 and n-6 PUFA metabolism. The LM of 437 slaughter pigs was
      analyzed for FA composition (expressed as g/100 g of FA). Indices for enzyme
      activities were calculated from product to precursor FA ratios. Genetic
      parameters were estimated with single- and multi-trait animal models. The total
      FA content, reflecting the intramuscular fat content, was either included or not
      in the model. Results from the models without total FA content showed relatively
      high heritability estimates, generally above 0.50, for the proportion of the most
      important MUFA and PUFA, compared with much smaller values for the SFA. When
      total FA content was included in the models, heritability values decreased (P <
      0.001) for most individual FA and for all sums of FA groups, except for C18:0,
      C18:3n-6, and C18:3n-3. Heritability estimates for the ratios C20:4n-6/C18:2n-6
      and C22:6n-3/C18:3n-3, reflecting the overall conversion in the n-6 and n-3 PUFA
      pathway, respectively, were 0.29 and 0.35, respectively, with total FA content in
      the model and increased to 0.38 and 0.49, respectively, if total FA content was
      not in the model. Heritabilities for other more specific indices were of the same
      order. Genetic correlations between PUFA proportions and indices for enzyme
      activities with ADG were mostly negative, whereas the correlations with carcass
      lean meat percentage were mostly positive. It was concluded that there is
      meaningful genetic variation for long-chain PUFA metabolism that is only partly
      dependent on the carcass and muscle fat content. This may allow selection for
      improved FA composition of pork.

PMID- 20042549
TI  - Mammalian glutathione peroxidases control acquisition and maintenance of
      spermatozoa integrity.
AB  - In mammals, posttesticular epididymal sperm maturation is considered an essential
      step in the transformation of immature testicular gametes to mature spermatozoa
      capable of fertilization. Reactive oxygen species (ROS) have been shown to be key
      actors in this maturation process, and it is now clear that ROS are central for
      sperm physiology in processes such as sperm maturation and capacitation. However,
      during epididymal maturation and storage and until the onset of fertilization,
      oxidative damage is a threat spermatozoa must face more than any other cells.
      Spermatozoa were found to be extremely sensitive to oxidative attacks correlated
      with lipid peroxidation, DNA damage, and impaired sperm motility, all affecting
      fertilization. To control the quantity of H(2)O(2) in the vicinity of male
      gametes, mammalian epididymis uses a panel of nonenzymatic and enzymatic
      scavengers, among which the glutathione peroxidase (GPx) family is largely
      represented. Among the various GPx proteins expressed in the mammalian
      epididymis, GPx4 and GPx5 occupy unique positions and functions that are reviewed
      in this paper. This paper underlines the importance of the GPx protein family in
      determining the fertilizing potential of mammalian spermatozoa. This is
      particularly relevant in the field of mammalian fertility and infertility as well
      as in the development of assisted medical procreation technologies and male
      gamete preservation techniques that are extensively used in human and animal
      reproduction programs.

PMID- 20042550
TI  - Comparative effects of ractopamine hydrochloride and zilpaterol hydrochloride on
      growth performance, carcass traits, and longissimus tenderness of finishing
      steers.
AB  - Ractopamine hydrochloride (RAC) and zilpaterol hydrochloride (ZH) are beta
      adrenergic agonists that improve growth performance and affect carcass
      characteristics. The objective of this study was to evaluate the comparative
      effects of RAC and ZH when fed to beef steers during the last 33 d of the
      finishing period. Three hundred crossbred beef steers (516 +/- 8 kg) were grouped
      by BW, BCS, and breed type and randomly assigned to 1 of 3 treatments (10 steers
      per pen; 10 pens per treatment). Treatments were control (no beta-agonists
      added), RAC (200 mg of ractopaminexhdx(-1)d(-1), for 33 d), or ZH (75 mg of
      zilpaterolxanimalx(-1)d(-1), for 30 d, removed 3 d for required withdrawal
      period). Steers were slaughtered, carcass characteristics were evaluated, and cut
      out yields were determined. Both RAC and ZH increased final BW, ADG, feed
      efficiency (G:F), and HCW compared with controls (P < 0.05). Compared with RAC,
      ZH decreased ADG, ADFI, and final BW, but increased HCW and dressing percentage
      (P < 0.05). Carcass yield was not affected by RAC in this experiment, whereas ZH
      decreased adjusted fat thickness and KPH, increased ribeye area, improved yield
      grade, and increased cut-out yields, when compared with controls (P < 0.05).
      Marbling, lean maturity, and skeletal maturity were not different between
      treatments (P > 0.05). Steaks from RAC steers had greater (P < 0.05) Warner
      Bratzler shear force (WBSF) values than steaks from control steers at 3 and 7 d
      of aging, but did not differ from controls after 14 d of aging. Steaks from ZH
      steers had greater WBSF values (P < 0.05) than steaks from controls and RAC
      steaks throughout the 21-d postmortem aging period. Although both beta-adrenergic
      agonists were effective at improving feedlot performance, RAC showed no negative
      effect on WBSF after 14 d, whereas WBSF values for ZH steaks were significantly
      greater than controls after 21 d.

PMID- 20042551
TI  - Comparison of 3 tall fescue-based stocker systems.
AB  - A 2-yr production study was conducted to evaluate 3 systems of growing stocker
      calves under rotational stocking. One group of steers was stocked on pasture from
      early April to mid August (spring-stocked steers = SSS), and another group of
      steers was stocked from early July to late October (fall-stocked steers = FSS).
      Steers were stratified by BW (n = 72, BW = 229 +/- 11 kg for SSS; n = 72, BW =
      248 +/- 18 kg for FSS) and randomly assigned to 1 of 3 treatments. The 3
      treatments were 1) rotationally stocked only (control; CON), steers rotated to a
      new paddock as forage availability dropped below acceptable levels in the
      occupied paddock; 2) rotationally stocked with distillers grains (DIST); this was
      the same as CON except steers were supplemented with varying amounts of
      distillers dried grains with solubles (DDGS) based on forage nutritive value; and
      3) rotationally stocked with round-bale silage (SIL); excess forage in spring was
      harvested and stored as round-bale silage and fed back as needed. Total BW
      gain/ha over the entire grazing season did not differ between DIST and SIL (P =
      0.09) steers, but both were greater than CON (P < 0.01). Total BW gain/ha for
      DIST, SIL, and CON was 459 (SEM = 11.5), 402 (SEM = 31.0), and 276 (SEM = 26.2)
      kg, respectively. For ADG, there was a group x year (P < 0.01) and group x
      treatment (P = 0.02) interaction. Steer ADG for SSS did not differ between SIL
      and DIST (P = 0.51), but was greater than the CON (P = 0.01). The ADG for SSS was
      0.79 (SEM = 0.04), 0.81 (SEM = 0.05), and 0.62 (SEM = 0.05) kg for DIST, SIL, and
      CON, respectively. For the FSS, ADG for all 3 treatments was different (P =
      0.02). The FSS ADG was 0.72 (SEM = 0.03), 0.53 (SEM = 0.04), and 0.29 (SEM =
      0.04) kg for DIST, SIL, and CON, respectively. The only treatment with equivalent
      (P = 0.07) ADG between early and late-stocked steers (SSS vs. FSS) was DIST.
      Adjusting the amount of DDGS supplemented to steers based on forage nutritive
      value resulted in consistent BW gains throughout the grazing study, whereas
      steers in the SIL and CON treatments gained less BW during the latter portion of
      the season. Controlling forage maturity by removal in the SIL treatment resulted
      in total BW gains/ha that were not different than the DIST treatment.

PMID- 20042552
TI  - Effect of virginiamycin on the apparent ileal digestibility of amino acids by
      growing pigs.
AB  - The objective of this experiment was to measure the influence of virginiamycin on
      the apparent ileal digestibility (AID) of AA by growing pigs. Fifteen barrows
      were surgically equipped with a T-cannula in the distal ileum and used in the
      experiment (initial BW = 35.0 +/- 2.7 kg). Animals were randomly allotted to 3
      dietary treatments with 5 pigs per treatment during a 6-wk experiment. Dietary
      treatments included 1) a basal corn-soybean meal diet, 2) the basal diet
      supplemented with 11 mg/kg of virginiamycin, and 3) the basal diet supplemented
      with 22 mg/kg of virginiamycin. Pigs were fed their respective treatment diets
      during wk 2, 3, and 4, but during wk 1, 5, and 6, all pigs were fed the basal
      diet. Ileal samples were collected on d 6 and 7 of each week. Results showed that
      the AID of all indispensable AA, except Arg, His, and Ile, increased (P < 0.05)
      during wk 2, 3, and 4 compared with wk 1 in pigs fed the diet containing 11 mg/kg
      of virginiamycin. Pigs fed 22 mg/kg of virginiamycin during wk 2, 3, and 4 had
      increased (P < 0.05) AID of Trp and Val during these weeks compared with the AID
      in wk 1. However, the increased AID of AA did not carry over to wk 5 and 6, when
      virginiamycin was withdrawn from the diet, regardless of the inclusion rate. In
      pooled data from wk 2, 3, and 4, the AID of CP, the mean of all indispensable AA,
      and Ile, Leu, Met, Phe, Trp, and Val increased (linear, P < 0.05) as
      virginiamycin was added to the diets, whereas a tendency (P < 0.10) for a linear
      or quadratic increase was observed for His, Lys, and Thr. These results indicate
      that addition of virginiamycin to corn-soybean meal diets fed to growing pigs
      increases the AID of AA, but this effect is not maintained after the removal of
      virginiamycin from the diet.

PMID- 20042553
TI  - 39-year-old woman with an obscure case of anemia.

PMID- 20042554
TI  - Medical images. Pancreatic adenocarcinoma?

PMID- 20042555
TI  - Delirium: a cognitive cost of the comfort of procedural sedation in elderly
      patients?

PMID- 20042556
TI  - The physiognomy of Mayo Clinic Proceedings, 2010.

PMID- 20042557
TI  - Sedation depth during spinal anesthesia and the development of postoperative
      delirium in elderly patients undergoing hip fracture repair.
AB  - OBJECTIVE: To determine whether limiting intraoperative sedation depth during
      spinal anesthesia for hip fracture repair in elderly patients can decrease the
      prevalence of postoperative delirium. PATIENTS AND METHODS: We performed a double
      blind, randomized controlled trial at an academic medical center of elderly
      patients (>or=65 years) without preoperative delirium or severe dementia who
      underwent hip fracture repair under spinal anesthesia with propofol sedation.
      Sedation depth was titrated using processed electroencephalography with the
      bispectral index (BIS), and patients were randomized to receive either deep (BIS,
      approximately 50) or light (BIS, >or=80) sedation. Postoperative delirium was
      assessed as defined by Diagnostic and Statistical Manual of Mental Disorders
      (Third Edition Revised) criteria using the Confusion Assessment Method beginning
      at any time from the second day after surgery. RESULTS: From April 2, 2005,
      through October 30, 2008, a total of 114 patients were randomized. The prevalence
      of postoperative delirium was significantly lower in the light sedation group
      (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1
      incident of delirium will be prevented for every 4.7 patients treated with light
      sedation. The mean +/- SD number of days of delirium during hospitalization was
      lower in the light sedation group than in the deep sedation group (0.5+/-1.5 days
      vs 1.4+/-4.0 days; P=.01). CONCLUSION: The use of light propofol sedation
      decreased the prevalence of postoperative delirium by 50% compared with deep
      sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe,
      and cost-effective intervention for preventing postoperative delirium in elderly
      patients that could be widely and readily adopted.

PMID- 20042558
TI  - Analysis of guidelines for screening diabetes mellitus in an ambulatory
      population.
AB  - OBJECTIVES: To compare the case-finding ability of current national guidelines
      for screening diabetes mellitus and characterize factors that affect testing
      practices in an ambulatory population. PATIENTS AND METHODS: In this
      retrospective analysis, we reviewed a database of 46,991 nondiabetic patients
      aged 20 years and older who were seen at a large Midwestern academic physician
      practice from January 1, 2005, through December 31, 2007. Patients were included
      in the sample if they were currently being treated by the physician group
      according to Wisconsin Collaborative for Healthcare Quality criteria. Pregnant
      patients, diabetic patients, and patients who died during the study years were
      excluded. The prevalence of patients who met the American Diabetes Association
      (ADA) and/or US Preventive Services Task Force (USPSTF) criteria for diabetes
      screening, percentage of these patients screened, and number of new diabetes
      diagnoses per guideline were evaluated. Screening rates were assessed by number
      of high-risk factors, primary care specialty, and insurance status. RESULTS: A
      total of 33,823 (72.0%) of 46,991 patients met either the ADA or the USPSTF
      screening criteria, and 28,842 (85.3%) of the eligible patients were tested. More
      patients met the ADA criteria than the 2008 USPSTF criteria (30,790 [65.5%] vs
      12,054 [25.6%]), and the 2008 USPSTF guidelines resulted in 460 fewer diagnoses
      of diabetes (33.1%). By single high-risk factor, prediabetes (15.8%) and
      polycystic ovarian syndrome (12.6%) produced the highest rates of diagnosis. The
      number of ADA high-risk factors predicted diabetes, with 6 (23%) of 26 patients
      with 6 risk factors diagnosed as having diabetes. Uninsured patients were tested
      significantly less often than insured patients (54.9% vs 85.4%). CONCLUSION:
      Compared with the ADA recommendations, the new USPSTF guidelines result in a
      lower number of patients eligible for screening and decrease case finding
      significantly. The number and type of risk factors predict diabetes, and lack of
      health insurance decreases testing.

PMID- 20042559
TI  - Relationship between obesity and incident diabetes in middle-aged and older
      Japanese adults: the Ibaraki Prefectural Health Study.
AB  - OBJECTIVE: To investigate the age-specific relationship between body mass index
      (BMI) and risk of diabetes in a Japanese general population. PARTICIPANTS AND
      METHODS: A cohort of Japanese men (N=19,926) and women (N=41,489) (aged 40-79
      years) who under went community-based health checkups in 1993 and were free of
      diabetes was followed up by annual examinations with measurement of blood glucose
      concentrations until the end of 2006. Incident diabetes mellitus was defined as a
      blood glucose concentration of 126 mg/dL or greater under fasting conditions, 200
      mg/dL or greater under nonfasting conditions, or diabetic medication use at
      baseline. Hazard ratios (HRs) for diabetes according to BMI were estimated using
      a Cox proportional hazard model. The model was adjusted for possible confounding
      variables. RESULTS: A total of 4429 participants (7.2%) developed diabetes (2065
      men and 2364 women) during a mean follow-up of 5.5 years. Compared with those
      with a BMI of less than 25.0, the multivariate HRs for diabetes among
      participants with a BMI of 30.0 or greater were 1.40 (95% confidence interval
      [CI], 0.89-2.20) for men aged 40 to 59 years and 1.26 (95% CI, 0.81-1.96) for men
      aged 60 to 79 years (P=.002 for interaction). The HRs were 2.50 (95% CI, 2.01
      3.11) for women aged 40 to 59 years and 1.80 (95% CI, 1.41-2.30) for women aged
      60 to 79 years (P=.04 for interaction). CONCLUSION: The effect of obesity on the
      risk of diabetes is greater for middle-aged than for older adults.

PMID- 20042560
TI  - Association between albuminuria and duration of diabetes and myocardial
      dysfunction and peripheral arterial disease among patients with stable coronary
      artery disease in the BARI 2D study.
AB  - OBJECTIVE: To evaluate the effect of prior duration of diabetes, glycated
      hemoglobin level at study entry, and microalbuminuria or macroalbuminuria on the
      extent and severity of coronary artery disease (CAD) and peripheral arterial
      disease. PATIENTS AND METHODS: We studied baseline characteristics of the 2368
      participants of the BARI 2D (Bypass Angioplasty Revascularization Investigation 2
      Diabetes) study, a randomized clinical trial that evaluates treatment efficacy
      for patients with type 2 diabetes and angiographically documented stable CAD.
      Patients were enrolled from January 1, 2001, through March 31, 2005. Peripheral
      arterial disease was ascertained by an ankle-brachial index (ABI) of 0.9 or less,
      and extent of CAD was measured by presence of multivessel disease, a left
      ventricular ejection fraction (LVEF) of less than 50%, and myocardial jeopardy
      index. RESULTS: Duration of diabetes of 20 or more years was associated with
      increased risk of ABI of 0.9 or less (odds ratio [OR], 1.54; 95% confidence
      interval [CI], 1.04-2.26), intermittent claudication (OR, 1.61; 95% CI, 1.10
      2.35), and LVEF of less than 50% (OR, 2.03; 95% CI, 1.37-3.02). Microalbuminuria
      was associated with intermittent claudication (OR, 1.53; 95% CI, 1.16-2.02) and
      ABI of 0.9 or less (OR, 1.31; 95% CI, 0.98-1.75), whereas macroalbuminuria was
      associated with abnormal ABI, claudication, and LVEF of less than 50%. There was
      a significant association between diabetes duration and extent of CAD as
      manifested by number of coronary lesions, but no other significant associations
      were observed between duration of disease, glycated hemoglobin levels, or albumin
      to-creatinine ratio and other manifestations of CAD. CONCLUSION: Duration of
      diabetes and microalbuminuria or macroalbuminuria are important predictors of
      severity of peripheral arterial disease and left ventricular dysfunction in a
      cohort of patients selected for the presence of CAD.

PMID- 20042561
TI  - Hospitalized patients' understanding of their plan of care.
AB  - OBJECTIVE: To evaluate hospitalized patients' understanding of their plan of
      care. PATIENTS AND METHODS: Interviews of a cross-sectional sample of
      hospitalized patients and their physicians were conducted from June 6 through
      June 26, 2008. Patients were asked whether they knew the name of the physician
      and nurse responsible for their care and specific questions about 6 aspects of
      the plan of care for the day (primary diagnosis, planned tests, planned
      procedures, medication changes, physician services consulted, and the expected
      length of stay). Physicians were interviewed and asked about the plan of care in
      the same fashion as for the patients. Two board-certified internists reviewed
      responses and rated patient-physician agreement on each aspect of the plan of
      care as none, partial, or complete agreement. RESULTS: Of 250 eligible patients,
      241 (96%) agreed to be interviewed. A total of 233 (97%) of 241 physicians
      completed the interview, although sample sizes vary because of missing data
      elements. Of 239 patients, 77 (32%) correctly named at least 1 of their hospital
      physicians, and 143 patients (60%) correctly named their nurses. For each aspect
      of care, patients and physicians lacked agreement on the plan of care in a large
      number of instances. Specifically, there was no agreement between patients and
      physicians on planned tests or procedures for the day in 87 (38%) of 231
      [corrected] instances and in 22 (10%) of 231 [corrected] instances. Complete
      agreement on the anticipated length of stay occurred in only 85 (39%) of 218
      instances. CONCLUSION: A substantial portion of hospitalized patients do not
      understand their plan of care. Patients' limited understanding of their plan of
      care may adversely affect their ability to provide informed consent for hospital
      treatments and to assume their own care after discharge.

PMID- 20042562
TI  - Patient participation: current knowledge and applicability to patient safety.
AB  - Patient participation is increasingly recognized as a key component in the
      redesign of health care processes and is advocated as a means to improve patient
      safety. The concept has been successfully applied to various areas of patient
      care, such as decision making and the management of chronic diseases. We review
      the origins of patient participation, discuss the published evidence on its
      efficacy, and summarize the factors influencing its implementation. Patient
      related factors, such as acceptance of the new patient role, lack of medical
      knowledge, lack of confidence, comorbidity, and various sociodemographic
      parameters, all affect willingness to participate in the health care process.
      Among health care workers, the acceptance and promotion of patient participation
      are influenced by other issues, including the desire to maintain control, lack of
      time, personal beliefs, type of illness, and training in patient-caregiver
      relationships. Social status, specialty, ethnic origin, and the stakes involved
      also influence patient and health care worker acceptance. The London Declaration,
      endorsed by the World Health Organization World Alliance for Patient Safety,
      calls for a greater role for patients to improve the safety of health care
      worldwide. Patient participation in hand hygiene promotion among staff to prevent
      health care-associated infection is discussed as an illustrative example. A
      conceptual model including key factors that influence participation and invite
      patients to contribute to error prevention is proposed. Further research is
      essential to establish key determinants for the success of patient participation
      in reducing medical errors and in improving patient safety.

PMID- 20042564
TI  - Vulvovaginal atrophy.
AB  - Vulvovaginal atrophy (VVA) is a common and underreported condition associated
      with decreased estrogenization of the vaginal tissue. Symptoms include dryness,
      irritation, soreness, and dyspareunia with urinary frequency, urgency, and urge
      incontinence. It can occur at any time in a woman's life cycle, although more
      commonly in the postmenopausal phase, during which the prevalence is close to
      50%. Clinical findings include the presence of pale and dry vulvovaginal mucosa
      with petechiae. Vaginal rugae disappear, and the cervix may become flush with the
      vaginal wall. A vaginal pH of 4.6 or more supports the diagnosis of VVA. Even
      while taking systemic estrogen, 10% to 20% of women may still have residual VVA
      symptoms. Breast cancer treatment increases the prevalence of VVA because the
      surgical, endocrine, and chemotherapeutic agents used in its treatment can cause
      or exacerbate VVA. Local estrogen treatment for this group of women remains
      controversial.

PMID- 20042563
TI  - New developments in the medical management of prostate cancer.
AB  - Prostate cancer is a substantial public health burden and a leading cause of
      cancer-related morbidity and mortality in the United States despite the
      observation that annual prostate cancer-specific mortality rates have been
      declining during the previous decade. Although the reasons for this positive
      development are unclear, a combination of factors may have contributed. This
      update will review ongoing developments and summarize therapeutic advances in
      prostate cancer treatment on the basis of the current understanding of prostate
      cancer biology. Literature for this review was selected in 2009 by searching
      PubMed for the following keywords: prostatic neoplasms, castration, androgen
      receptor, hormonal, and chemotherapy. Emphasis is placed on published clinical
      studies in advanced prostate cancer therapeutics in the past 5 to 10 years. Also
      included in the review are novel hormonal agents targeting the androgen receptor
      currently in development for the treatment of advanced prostate cancer.

PMID- 20042565
TI  - 73-year-old woman with progressive shortness of breath.

PMID- 20042566
TI  - Role of oral agents in improving cardiovascular prognosis in diabetes mellitus.

PMID- 20042567
TI  - Optimal medical management of acute attacks of acquired angioedema.

PMID- 20042568
TI  - Medical images. Flip-flop heart.

PMID- 20042569
TI  - TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88
      independent, whereas MyD88 is required to clear infection.
AB  - Porphyromonas gingivalis is a gram-negative anaerobe considered to be a major
      periodontal pathogen. TLR2 plays a central role in the response to P. gingivalis
      infection in vivo. In its absence there is a weak inflammatory response; however,
      bacteria are cleared rapidly compared with wild-type mice. We examined the role
      of the TLR adaptor proteins MyD88 and TLR/IL-1R-domain-containing adaptor
      inducing IFN-beta in the inflammatory response to P. gingivalis in vivo and in
      the ability to clear the bacterial infection. Proinflammatory cytokine production
      in response to P. gingivalis infection depends on TLR2, but it does not require
      MyD88 or TLR/IL-1R-domain-containing adaptor-inducing IFN-beta. In contrast, the
      generation of intracellular toxic oxygen species and the ultimate clearance of P.
      gingivalis infection depend critically on MyD88, independent of TLR2. Thus,
      robust cytokine production and bacterial clearance are independent events
      mediated by distinct signaling pathways following infection with P. gingivalis.

PMID- 20042571
TI  - Mycolactone suppresses T cell responsiveness by altering both early signaling and
      posttranslational events.
AB  - Mycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the
      causative agent of a necrotizing skin disease referred to as Buruli ulcer.
      Intriguingly, patients with progressive lesions display a systemic suppression of
      Th1 responses that resolves on surgical excision of infected tissues. In this
      study, we examined the effects of mycolactone on the functional biology of T
      cells and identified two mechanisms by which mycolactone suppresses cell
      responsiveness to antigenic stimulation. At noncytotoxic concentrations,
      mycolactone blocked the activation-induced production of cytokines by a
      posttranscriptional, mammalian target of rapamycin, and cellular stress
      independent mechanism. In addition, mycolactone triggered the lipid-raft
      association and activation of the Src-family kinase, Lck. Mycolactone-mediated
      hyperactivation of Lck resulted in the depletion of intracellular calcium stores
      and downregulation of the TCR, leading to impaired T cell responsiveness to
      stimulation. These biochemical alterations were not observed when T cells were
      exposed to other bacterial lipids, or to structurally related immunosuppressors.
      Mycolactone thus constitutes a novel type of T cell immunosuppressive agent, the
      potent activity of which may explain the defective cellular responses in Buruli
      ulcer patients.

PMID- 20042572
TI  - A single TCR alpha-chain with dominant peptide recognition in the allorestricted
      HER2/neu-specific T cell repertoire.
AB  - T cells can recognize tumor cells specifically by their TCR and the transfer of
      TCR-engineered T cells is a promising novel tool in anticancer therapies. We
      isolated and characterized four allorestricted TCRs with specificity for the
      HER2/neu-derived peptide 369 (HER2(369)) demonstrating high peptide specificity.
      PBMCs transduced with especially one TCR, HER2-1, mediated specific tumor
      reactivity after TCR optimization suggesting that this TCR represents a potential
      candidate for targeting HER2 by TCR-transduced effector cells. Another TCR showed
      high-peptide specificity without tumor reactivity. However, the TCR alpha-chain
      of this TCR specifically recognized HER2(369) not only in combination with the
      original beta-chain but also with four other beta-chains of the same variable
      family deriving from TCRs with diverse specificities. Pairing with one beta-chain
      derived from another HER2(369)-specific TCR potentiated the chimeric TCRs in
      regard to functional avidity, CD8 independency, and tumor reactivity. Although
      the frequency of such TCR single chains with dominant peptide recognition is
      currently unknown, they may represent interesting tools for TCR optimization
      resulting in enhanced functionality when paired to novel partner chains. However,
      undirected mispairing with novel partner chains may also result in enhanced cross
      reactivity and self-reactivity. These results may have an important impact on the
      further design of strategies for adoptive transfer using TCR-transduced T cells.

PMID- 20042570
TI  - Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment
      during inflammation.
AB  - Macrophage recruitment to sites of inflammation is an essential step in host
      defense. However, the mechanisms preventing excessive accumulation of macrophages
      remain relatively unknown. The lysophospholipid sphingosine 1-phosphate (S1P)
      promotes T and B cell egress from lymphoid organs by acting on S1P receptor 1
      (S1P(1)R). More recently, S1P(5)R was shown to regulate NK cell mobilization
      during inflammation, raising the possibility that S1P regulates the trafficking
      of other leukocyte lineages. In this study, we show that S1P(2)R inhibits
      macrophage migration in vitro and that S1P(2)R-deficient mice have enhanced
      macrophage recruitment during thioglycollate peritonitis. We identify the
      signaling mechanisms used by S1P(2)R in macrophages, involving the second
      messenger cAMP and inhibition of Akt phosphorylation. In addition, we show that
      the phosphoinositide phosphatase and tensin homolog deleted on chromosome 10,
      which has been suggested to mediate S1P(2)R effects in other cell types, does not
      mediate S1P(2)R inhibition in macrophages. Our results suggest that S1P serves as
      a negative regulator of macrophage recruitment by inhibiting migration in these
      cells and identify an additional facet to the regulation of leukocyte trafficking
      by S1P.

PMID- 20042573
TI  - A recombinant bispecific single-chain fragment variable specific for HLA class II
      and Fc alpha RI (CD89) recruits polymorphonuclear neutrophils for efficient lysis
      of malignant B lymphoid cells.
AB  - Bispecific Abs offer new perspectives for cancer immunotherapy. In this study, we
      describe a recombinant bispecific single-chain fragment variable (bsscFv)
      directed against Fc alpha RI (CD89) on polymorphonuclear neutrophils (PMNs) or
      monocytes/macrophages and HLA class II on lymphoma target cells. Fc alpha RI and
      HLA class II-directed single-chain fragment variable (scFv) fragments were
      isolated from phage display libraries, established from the hybridomas A77 and
      F3.3, respectively. The two scFv molecules were connected with a 20 aa flexible
      linker sequence. After expression in SF21 insect cells and chromatographic
      purification, the bispecific molecule showed specific binding to both Ags at K(D)
      values of 148 +/- 42 nM and 113 +/- 25 nM for the anti-Fc alpha RI and anti-HLA
      class II scFv components in the bsscFv, respectively. In Ab-dependent
      cytotoxicity assays with PMNs as effectors and a series of lymphoma-derived cell
      lines (ARH-77, RAJI, REH, NALM-6, RS4;11), the bsscFv was significantly more
      cytotoxic than the parental murine IgG1 and its chimeric IgG1 derivative. When
      targeting primary tumor cell isolates from six patients with B cell malignancies,
      the killing capacity of the (Fc alphaRI x HLA class II) bsscFv compared favorably
      to conventional HLA class II mAb. Importantly, the cell lines NALM-6 and RS411,
      as well as two primary tumor cell isolates, were exclusively lysed by the bsscFv.
      To our knowledge, this is the first report of an Fc alpha RI-directed bsscFv
      effectively recruiting PMNs for redirected cytotoxicity against human B cell
      malignancies. Our data show that an (Fc alpha RI x HLA class II) bsscFv is an
      interesting candidate for further engineering of small, modular
      immunopharmaceuticals.

PMID- 20042574
TI  - Regulation of Fc epsilon RI expression during murine basophil maturation: the
      interplay between IgE, cell division, and Fc epsilon RI synthetic rate.
AB  - Expression of Fc epsilonRI on basophils and mast cells is modulated by IgE Ab.
      Previous studies have noted in vivo receptor expression dynamics that are
      discordant with expectations derived from in vitro studies. The current study
      presents a formal hypothesis to explain the discordant observations and tests two
      assumptions that underlie a proposed model of receptor dynamics. After first
      showing that a murine model of receptor expression on basophils recapitulates
      observations made using human basophils, the effect of changes in IgE on basophil
      egress rates was examined. In the proposed model, egress rates from bone marrow
      (BM) were assumed to be unaffected by changes in IgE concentration. Egress was
      tested by examining the labeling of BM and peripheral blood (BL) basophils at
      various times after injection of BrdU with and without injection with IgE. The
      IgE Ab did not alter the appearance of BrdU label in peripheral BL basophils. In
      addition, BM and BL basophils were responsive to the elevations in IgE, with
      receptor expression increasing on BM basophils before BL basophils. It was also
      noted that BL basophils expressed approximately 50% of the receptor density of BM
      basophils. There was a 3-fold greater synthetic rate of Fc epsilonRI on BM
      basophils that readily explained the difference. These results provide support
      for the proposed hypothesis of rapid changes in receptor expression being
      controlled by cell replacement. The studies also support a model whereby receptor
      expression is limited by cell division and that basophils, once mature, slow
      their rate of receptor synthesis.

PMID- 20042575
TI  - LL-37 promotes rapid sensing of CpG oligodeoxynucleotides by B lymphocytes and
      plasmacytoid dendritic cells.
AB  - LL-37 is a cationic antimicrobial peptide derived from neutrophils and
      keratinocytes. It plays an important role in protection against bacterial
      infection in the skin and mucosal surfaces. However, its role within the blood
      compartment remains unclear given that serum inhibits its bactericidal property.
      In this study, we show that LL-37 promotes very rapid and highly efficient
      sensing of CpG motifs in bacterial DNA by human B lymphocytes and plasmacytoid
      dendritic cells (pDCs) in serum-containing media and in whole blood. LL-37
      allowed detection of CpG oligodeoxynucleotide (ODN) within minutes of exposure.
      Without LL-37, 20-30 times more CpG was required to produce the same effect. The
      promotion of CpG detection by LL-37 was independent of the backbone of the ODN,
      as the effect was observed not only in ODNs with modified phosphorothioate
      backbone, but also in ODNs with natural phosphodiester backbone, as found in
      genomic DNA. Unmethylated CpG motifs within the phosphodiester ODN and LL-37
      mediated delivery are required for pDCs to respond. In keeping with the above,
      cells responded to CpG-rich bacterial DNA and LL-37, but not to human DNA and LL
      37. The ability of LL-37 to enhance delivery of CpG to stimulate immune cells is
      independent of its amphipathic structure and its bactericidal property. LL-37
      aids the delivery of CpG to B cells and pDCs, but not T cells. These findings are
      pertinent to rapid recognition of microbial DNA and are highly relevant to
      contemporary studies of CpG/TLR9 agonists in vaccines and cancer therapy.

PMID- 20042576
TI  - SHP-1 deficient mast cells are hyperresponsive to stimulation and critical in
      initiating allergic inflammation in the lung.
AB  - Phosphatase Src homology region 2 domain-containing phosphatase 1 (SHP-1)
      deficient mice display an allergic asthma phenotype that is largely IL-13 and
      STAT6 dependent. The cell types responsible for the Th2 phenotype have not been
      identified. We hypothesized that SHP-1 deficiency leads to mast cell
      dysregulation and increased production and release of mediators and Th2
      cytokines, leading to the allergic asthma phenotype. We examined SHP-1 regulation
      of mast cell differentiation, survival, and functional responses to stimulation
      using bone marrow-derived mast cells from viable motheaten (mev) mice. We
      assessed pulmonary phenotypical changes in mev mice on the mast cell-deficient
      Kit(W-Sh) genetic background. The results showed that SHP-1 deficiency led to
      increased differentiation and survival, but reduced proliferation, of mast cells.
      SHP-1-deficient mast cells produced and released increased amounts of mediators
      and Th2 cytokines IL-4 and -13 spontaneously and in response to H(2)O(2), LPS,
      and Fc epsilonI cross-linking, involving c-Kit-dependent and -independent
      processes. The Fc epsilonRI signaling led to binding of SHP-1 to linker for
      activation of T cells 2 and enhanced linker for activation of T cells 2
      phosphorylation in mev bone marrow-derived mast cells. Furthermore, the number of
      mast cells in the lung tissue of mev mice was increased and mast cell production
      and release of Th2 cytokines were distinctly increased upon Fc epsilonRI
      stimulation. When backcrossed to the Kit(W-Sh) background, mev mice had markedly
      reduced pulmonary inflammation and Th2 cytokine production. These findings
      demonstrate that SHP-1 is a critical regulator of mast cell development and
      function and that SHP-1-deficient mast cells are able to produce increased Th2
      cytokines and initiate allergic inflammatory responses in the lung.

PMID- 20042577
TI  - IL-33 induces IL-13-dependent cutaneous fibrosis.
AB  - IL-33 is constitutively expressed in epithelial barrier tissues, such as skin.
      Although increased expression of IL-33/IL-33R has been correlated with fibrotic
      disorders, such as scleroderma and progressive systemic sclerosis, the direct
      consequences of IL-33 release in skin has not been reported. To determine the
      effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and
      monitored its effects at the injection site. Administration of IL-33 resulted in
      IL-33R-dependent accumulation of eosinophils, CD3(+) lymphocytes, F4/80(+)
      mononuclear cells, increased expression of IL-13 mRNA, and the development of
      cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33
      resulted in significant modulation of a number of extracellular matrix-associated
      genes, including collagen VI, collagen III, and tissue inhibitor of
      metalloproteases-1. We establish that IL-33-induced fibrosis requires IL-13 using
      IL-13 knockout mice and eosinophils using Delta dblGATA mice. We show that bone
      marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation,
      suggesting that eosinophil-derived IL-13 may promote IL-33-induced cutaneous
      fibrosis. Collectively, our results identify IL-33 as a previously unrecognized
      profibrotic mediator in skin and highlight the cellular and molecular pathways by
      which this pathology develops.

PMID- 20042578
TI  - IL-10 induction by Bordetella parapertussis limits a protective IFN-gamma
      response.
AB  - Bordetella parapertussis causes the prolonged coughing illness known as pertussis
      or whooping cough, persisting for weeks within the respiratory tracts of infected
      hosts but inducing a very poor T cell response relative to that induced by
      Bordetella pertussis, the more common cause of pertussis. In this study, we
      examine the contributions of cytokines involved in the clearance of B.
      parapertussis and immunomodulation that delays effective clearance. The slow
      elimination of this pathogen from the respiratory tracts of mice coincides with
      the gradual accumulation of CD4(+) T cells in the lungs and B. parapertussis
      responsive IFN-gamma-producing cells in the spleen. IFN-gamma-deficient mice were
      defective in the accumulation of leukocytes in lungs and in clearance of B.
      parapertussis from the lungs. In vitro B. parapertussis-stimulated macrophages
      produced IL-10, which inhibited the generation of the IFN-gamma response that is
      required for protection in vivo. As compared with wild-type mice, IL-10-deficient
      mice produced significantly higher levels of IFN-gamma, had higher numbers of
      leukocytes accumulated in the lungs, and cleared B. parapertussis more rapidly.
      Together, these data indicate that B. parapertussis induces the production of IL
      10, which facilitates its persistence within infected hosts by limiting a
      protective IFN-gamma response.

PMID- 20042579
TI  - Autoimmune disease in Lyn-deficient mice is dependent on an inflammatory
      environment established by IL-6.
AB  - Lyn-deficient mice develop Ab-mediated autoimmune disease resembling systemic
      lupus erythematosus where hyperactive B cells are major contributors to
      pathology. In this study, we show that an inflammatory environment is established
      in Lyn(-/-) mice that perturbs several immune cell compartments and drives
      autoimmune disease. Lyn(-/-) leukocytes, notably B cells, are able to produce IL
      6, which facilitates hyperactivation of B and T cells, enhanced myelopoiesis,
      splenomegaly, and, ultimately, generation of pathogenic autoreactive Abs. Lyn(-/
      ) dendritic cells show increased maturation, but this phenotype is independent of
      autoimmunity as it is reiterated in B cell-deficient Lyn(-/-) mice. Genetic
      deletion of IL-6 on a Lyn-deficient background does not alter B cell development,
      plasma cell accumulation, or dendritic cell hypermaturation, suggesting that
      these characteristics are intrinsic to the loss of Lyn. However, hyperactivation
      of B and T cell compartments, extramedullary hematopoiesis, expansion of the
      myeloid lineage and autoimmune disease are all ameliorated in Lyn(-/-)IL-6(-/-)
      mice. Importantly, our studies show that although Lyn(-/-) B cells may be
      autoreactive, it is the IL-6-dependent inflammatory environment they engender
      that dictates their disease-causing potential. These findings improve our
      understanding of the mode of action of anti-IL-6 and B cell-directed therapies in
      autoimmune and inflammatory disease treatment.

PMID- 20042580
TI  - Regulation of lentivirus neurovirulence by lipopolysaccharide conditioning:
      suppression of CXCL10 in the brain by IL-10.
AB  - Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause
      neurovirulence, which is largely mediated by innate immunity. To investigate the
      interactions between neurovirulence and repeated conditioning by innate immune
      activation, models of lentivirus infection were exposed to LPS. Gene expression
      in HIV-infected (HIV+) and control (HIV-) patient brains was compared by real
      time RT-PCR and immunocytochemistry. Supernatants from mock and HIV-infected
      monocyte-derived macrophages exposed to LPS were applied to human neurons. FIV
      infected (FIV+) and control (FIV-) animals were exposed repeatedly to LPS
      postinfection together with concurrent neurobehavioral testing, viral load, and
      host gene analyses. Brains from HIV+ individuals exhibited induction of
      CD3epsilon, CXCL10, and granzyme A expression (p < 0.05). Supernatants from HIV+
      monocyte-derived macrophages induced CXCL10 expression in neurons, which was
      diminished by IL-10 treatment (p < 0.05). LPS-exposed FIV+ animals demonstrated
      lower plasma and brain viral loads (p < 0.05). Neuronal CXCL10 expression was
      increased in FIV+ animals but was suppressed by LPS exposure, together with
      reduced brain CD3epsilon and granzyme A expression (p < 0.05). In conjunction
      with preserved NeuN-positive neuronal counts in parietal cortex (p < 0.05), FIV+
      animals exposed to LPS also showed less severe neurobehavioral deficits (p <
      0.05). Repeated LPS exposures suppressed CXCL10 in the brain and ensuing T cell
      infiltration with a concomitant reduction in neurovirulence. Thus, innate immune
      chronic conditioning exerted beneficial effects on neurovirulence through
      suppression of a specific chemotactic factor, CXCL10, mediated by IL-10, leading
      to reduced leukocyte infiltration and release of neurotoxic factors.

PMID- 20042581
TI  - Mammalian clock gene Cryptochrome regulates arthritis via proinflammatory
      cytokine TNF-alpha.
AB  - The mammalian clock genes, Period and Cryptochrome (Cry), regulate circadian
      rhythm. We show that circadian rhythmicity and rhythmic expression of Period in
      the nuclei of inflammatory synovial cells and spleen cells are disturbed in mouse
      models of experimental arthritis. Expressions of other clock genes, Bmal1 and
      Dbp, are also disturbed in spleen cells by arthritis induction. Deletion of Cry1
      and Cry2 results in an increase in the number of activated CD3(+) CD69(+) T cells
      and a higher production of TNF-alpha from spleen cells. When arthritis is
      induced, Cry1(-/-)Cry2(-/-) mice develop maximal exacerbation of joint swelling,
      and upregulation of essential mediators of arthritis, including TNF-alpha, IL
      1beta and IL-6, and matrix metalloproteinase-3. Wee-1 kinase is solely
      upregulated in Cry1(-/-)Cry2(-/-) mice, in line with upregulation of c-Fos and
      Wee-1 kinase in human rheumatoid arthritis. The treatment with anti-TNF-alpha Ab
      significantly reduced the severity and halted the progression of the arthritis of
      Cry1(-/-)Cry2(-/-) mice and vice versa, ectopic expression of Cry1 in the mouse
      embryonic fibroblast from Cry1(-/-)Cry2(-/-) mice significantly reduced the trans
      activation of TNF-alpha gene. Thus, the biological clock and arthritis influence
      each other, and this interplay can influence human health and disease.

PMID- 20042582
TI  - Essential roles of IL-6 trans-signaling in colonic epithelial cells, induced by
      the IL-6/soluble-IL-6 receptor derived from lamina propria macrophages, on the
      development of colitis-associated premalignant cancer in a murine model.
AB  - Activation of the IL-6/Stat3 via IL-6 trans-signaling plays an important role in
      the pathogenesis of inflammatory bowel disease. Colitis-associated cancer (CAC)
      is a large bowel cancer and occurs with long-standing inflammatory bowel disease.
      The role of the IL-6/Stat3 in the development of CAC has not been fully
      understood. We investigate whether IL-6 trans-signaling contributes to the
      development of CAC using a mouse colitis-associated premalignant cancer (CApC)
      model. Chronic colitis (CC) was induced in BALB/c mice using dextran sodium
      sulfate. CApC was induced by dextran sodium sulfate treatment to CC-affected
      mice. IL-6 expression was determined by quantitative RT-PCR and
      immunofluorescence staining in colon. Phospho-Stat3 expression was examined by
      Western blotting and immunofluorescence analysis. The expression of IL-6
      receptors (i.e., the IL-6R alpha-chain and gp130) and tumor necrosis factor-alpha
      converting enzyme in the colon was examined by laser-capture microdissection and
      immunofluorescence staining. Soluble IL-6R alpha (sIL-6R alpha) was examined by
      Western blotting of epithelial cell-depleted colonic tissues. We also
      investigated whether a soluble gp130-Fc fusion protein could prevent CApC. IL-6
      expression was increased in the colon of CC- and CApC-affected mice and was
      restricted to lamina propria-macrophages. The expression of IL-6R alpha and tumor
      necrosis factor-alpha converting enzyme was increased in the lamina propria CD11b
      macrophages of CC-affected mice. sIL-6R alpha expression was also increased in
      these tissues. Reduced levels of IL-6R alpha generation were observed in the
      colonic epithelial cells of CC- and CApC-affected mice and were associated with
      the increased expression of gp130 and phospho-Stat3. Treatment with soluble
      gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells
      induced by macrophage-derived IL-6/sIL-6R alpha plays a crucial role in the
      development of CAC.

PMID- 20042583
TI  - Formation of a mast cell synapse: Fc epsilon RI membrane dynamics upon binding
      mobile or immobilized ligands on surfaces.
AB  - Fc epsilonRI on mast cells form a synapse when presented with mobile, bilayer
      incorporated Ag. In this study, we show that receptor reorganization within the
      contacting mast cell membrane is markedly different upon binding of mobile and
      immobilized ligands. Rat basophilic leukemia mast cells primed with fluorescent
      anti-DNP IgE were engaged by surfaces presenting either bilayer-incorporated,
      monovalent DNP-lipid (mobile ligand), or chemically cross-linked, multivalent DNP
      (immobilized ligand). Total internal reflection fluorescence imaging and electron
      microscopy methods were used to visualize receptor reorganization at the contact
      site. The spatial relationships of Fc epsilonRI to other cellular components at
      the synapse, such as actin, cholesterol, and linker for activation of T cells,
      were also analyzed. Stimulation of mast cells with immobilized polyvalent ligand
      resulted in typical levels of degranulation. Remarkably, degranulation also
      followed interaction of mast cells, with bilayers presenting mobile, monovalent
      ligand. Receptors engaged with mobile ligand coalesce into large, cholesterol
      rich clusters that occupy the central portion of the contacting membrane. These
      data indicate that Fc epsilonRI cross-linking is not an obligatory step in
      triggering mast cell signaling and suggest that dense populations of mobile
      receptors are capable of initiating low-level degranulation upon ligand
      recognition.

PMID- 20042584
TI  - T cell-dendritic cell interaction dynamics during the induction of respiratory
      tolerance and immunity.
AB  - Dendritic cells (DCs) residing in the lung are known to acquire inhaled Ag and,
      after migration to the draining bronchial lymph node (brLN), to present it to
      naive T cells in an either tolerogenic or immunogenic context. To visualize
      endogenous lung-derived DCs, we applied fluorescent latex beads (LXs)
      intratracheally, thereby in vivo labeling the majority of phagocytic cells within
      the lung. Of note, LX-bearing cells subsequently arriving in the draining brLN
      were found to represent lung-derived migratory DCs. Imaging explanted brLN by two
      photon laser-scanning microscopy, we quantitatively analyzed the migration and
      interaction behavior of naive CD4(+) T cells and endogenous, lung-derived DC
      presenting airway-delivered Ag under inflammatory or noninflammatory conditions.
      Ag-specific naive CD4(+) T cells engaged in stable as well as transient contacts
      with LX-bearing DCs in both situations and displayed similar overall motility
      kinetics, including a pronounced decrease in motility at 16-20 h after antigenic
      challenge. In contrast, the comparative analysis of T cell-DC cluster sizes as
      well as contact durations strongly suggests that lung-derived migratory DCs and
      naive CD4(+) T cells form more stable, long-lasting contacts under inflammatory
      conditions favoring the induction of respiratory immunity.

PMID- 20042586
TI  - Cutting edge: nucleotide-binding oligomerization domain 1-dependent responses
      account for murine resistance against Trypanosoma cruzi infection.
AB  - An effective innate immune recognition of the intracellular protozoan parasite
      Trypanosoma cruzi is critical for host resistance against Chagas disease, a
      severe and chronic illness that affects millions of people in Latin America. In
      this study, we evaluated the participation of nucleotide-binding oligomerization
      domain (Nod)-like receptor proteins in host response to T. cruzi infection and
      found that Nod1-dependent, but not Nod2-dependent, responses are required for
      host resistance against infection. Bone marrow-derived macrophages from Nod1(-/-)
      mice showed an impaired induction of NF-kappaB-dependent products in response to
      infection and failed to restrict T. cruzi infection in presence of IFN-gamma.
      Despite normal cytokine production in the sera, Nod1(-/-) mice were highly
      susceptible to T. cruzi infection, in a similar manner to MyD88(-/-) and NO
      synthase 2(-/-) mice. These studies indicate that Nod1-dependent responses
      account for host resistance against T. cruzi infection by mechanisms independent
      of cytokine production.

PMID- 20042585
TI  - Matrix metalloproteinase-8 inactivates macrophage inflammatory protein-1 alpha to
      reduce acute lung inflammation and injury in mice.
AB  - To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury
      (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8(-/-)
      mice versus wild-type (WT) mice or subjected the mice to hyperoxia (95% O(2)) and
      measured lung inflammation and injury at intervals. MMP-8(-/-) mice with ALI had
      greater increases in lung polymorphonuclear neutrophils (PMNs) and macrophage
      counts, measures of alveolar capillary barrier injury, lung elastance, and
      mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS
      treated MMP-8(-/-) mice had more MIP-1alpha than BALF from LPS-treated WT mice,
      but similar levels of other pro- and anti-inflammatory mediators. MIP-1alpha(-/-)
      mice with ALI had less acute lung inflammation and injury than WT mice with ALI,
      confirming that MIP-1alpha promotes acute lung inflammation and injury in mice.
      Genetically deleting MIP-1alpha in MMP-8(-/-) mice reduced the increased lung
      inflammation and injury and mortality in MMP-8(-/-) mice with ALI. Soluble MMP-8
      cleaved and inactivated MIP-1alpha in vitro, but membrane-bound MMP-8 on
      activated PMNs had greater MIP-1alpha-degrading activity than soluble MMP-8. High
      levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT
      mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has
      novel roles in restraining lung inflammation and in limiting alveolar capillary
      barrier injury during ALI in mice by inactivating MIP-1alpha. In addition,
      membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive
      form of the enzyme that limits lung inflammation and alveolar capillary barrier
      injury during ALI.

PMID- 20042587
TI  - Promoting immune responses by LIGHT in the face of abundant regulatory T cell
      inhibition.
AB  - CD4(+) regulatory T cell (Treg) populations are believed to play very important
      roles in the suppression of immune responses. Overriding Treg inhibition is
      necessary for initiating primary immune reaction upon inflammatory Ag
      stimulation. LIGHT, TNF superfamily member 14, has been shown to be a
      costimulatory molecule for effector T cells. Overexpression of lymphotoxin
      related inducible ligand that competes for glycoprotein D binding to herpesvirus
      entry mediator on T cells (LIGHT) on T cells induces strong T cell-mediated
      experimental intestinal inflammation. How this process is initiated by LIGHT in
      suppressive intestinal environments remains incompletely understood. In this
      study, we assessed the effect of LIGHT on Tregs. Our results indicate that LIGHT
      can support the expansion and function of Tregs. However, when LIGHT was highly
      expressed, these abundant Tregs failed to suppress the development of T cell
      mediated experimental colitis and antitumor immunity. We showed that this might
      be, in part, due to an ability of LIGHT to promote effector T cell proliferation
      and differentiation even in a Treg-abundant environment. Our data collectively
      suggest that LIGHT might be a critical cytokine involved in the development of
      autoimmune inflammatory diseases and that LIGHT-targeted immunotherapy might be
      useful in the treatment of these diseases.

PMID- 20042588
TI  - Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to
      HIV-1 infection.
AB  - There is limited knowledge on the identity of primary CD4(+) T cell subsets
      selectively targeted by HIV-1 in vivo. In this study, we established a link
      between HIV permissiveness, phenotype/homing potential, and lineage commitment in
      primary CD4(+) T cells. CCR4(+)CCR6(+), CCR4(+)CCR6(-), CXCR3(+)CCR6(+), and
      CXCR3(+)CCR6(-) T cells expressed cytokines and transcription factors specific
      for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4(+)CCR6(+) and
      CXCR3(+)CCR6(+) T cells expressed the HIV coreceptors CCR5 and CXCR4 and were
      permissive to R5 and X4 HIV replication. CCR4(+)CCR6(-) T cells expressed CXCR4
      but not CCR5 and were permissive to X4 HIV only. CXCR3(+)CCR6(-) T cells
      expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro.
      Total CCR6(+) T cells compared with CCR6(-) T cells harbored higher levels of
      integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of
      total CCR6(+) T cells and those of CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells
      were diminished in chronically infected HIV-positive subjects, despite viral
      suppressive therapy. A high-throughput analysis of cytokine profiles identified
      CXCR3(+)CCR6(+) T cells as a major source of TNF-alpha and CCL20 and demonstrated
      a decreased TNF-alpha/IL-10 ratio in CXCR3(+)CCR6(-) T cells. Finally,
      CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells exhibited gut- and lymph node-homing
      potential. Thus, we identified CCR4(+)CCR6(+) and CXCR3(+)CCR6(+) T cells as
      highly permissive to HIV replication, with potential to infiltrate and recruit
      more CCR6(+) T cells into anatomic sites of viral replication. It is necessary
      that new therapeutic strategies against HIV interfere with viral
      replication/persistence in discrete CCR6(+) T cell subsets.

PMID- 20042589
TI  - Critical role of IL-1 receptor-associated kinase-M in regulating chemokine
      dependent deleterious inflammation in murine influenza pneumonia.
AB  - Influenza virus is a common cause of respiratory infection and morbidity, which
      is often due to deleterious host immune responses directed against the pathogen.
      We investigated the role of IL-1 receptor-associated kinase-M (IRAK-M), an
      inhibitor of MyD88-dependent TLR signaling, in modulating the innate inflammatory
      response during influenza pneumonia using a murine model. The intranasal
      administration of influenza resulted in the upregulation of IRAK-M mRNA and
      protein levels in the lungs within 2 d after infectious challenge. Pulmonary
      influenza infection in mice deficient in IRAK-M (IRAK-M(-/-)) resulted in
      substantially increased mortality compared with similarly treated wild-type
      animals. Increased mortality in IRAK-M(-/-) mice was associated with enhanced
      early influx of neutrophils, high permeability edema, apoptosis of lung
      epithelial cells, markedly increased expression of inflammatory
      cytokines/chemokines, and release of neutrophil-derived enzymes, including
      myeloperoxidase and neutrophil elastase. Early viral clearance was not different
      in mutant mice, whereas viral titers in lungs and blood were significantly higher
      in IRAK-M(-/-) mice compared with wild-type animals. Increased lethality observed
      in IRAK-M(-/-) mice after influenza challenge was abrogated by Ab-mediated
      blockade of CXCR2. Collectively, our findings indicate that IRAK-M is critical to
      preventing deleterious neutrophil-dependent lung injury during influenza
      infection of the respiratory tract.

PMID- 20042590
TI  - Critical protective role for MCP-1 in pneumonic Burkholderia mallei infection.
AB  - Burkholderia mallei is a gram-negative bacterial pathogen of domestic equidae and
      humans that can cause severe, rapidly life-threatening pneumonic infections.
      Little is known regarding the role of chemokines and early cellular immune
      responses in protective immunity to pulmonary infection with B. mallei. Although
      the role of MCP-1 in gram-positive bacterial infections has been previously
      investigated, the role of MCP-1 in immunity to acute pneumonia caused by gram
      negative bacteria, such as B. mallei, has not been assessed. In a mouse model of
      pneumonic B. mallei infection, we found that both MCP-1(-/-) mice and CCR2(-/-)
      mice were extremely susceptible to pulmonary infection with B. mallei, compared
      with wild-type (WT) C57Bl/6 mice. Bacterial burden and organ lesions were
      significantly increased in CCR2(-/-) mice, compared with WT animals, following B.
      mallei challenge. Monocyte and dendritic cell recruitment into the lungs of CCR2(
      /-) mice was significantly reduced in comparison with that in WT mice following
      B. mallei infection, whereas neutrophil recruitment was actually increased.
      Depletion of monocytes and macrophages prior to infection also greatly raised the
      susceptibility of WT mice to infection. Production of IL-12 and IFN-gamma in the
      lungs after B. mallei infection was significantly impaired in both MCP-1(-/-) and
      CCR2(-/-) mice, whereas treatment of CCR2(-/-) mice with rIFN-gamma restored
      protection against lethal challenge with B. mallei. Thus, we conclude that MCP-1
      plays a key role in regulating cellular immunity and IFN-gamma production
      following pneumonic infection with B. mallei and therefore may also figure
      importantly in other gram-negative pneumonias.

PMID- 20042591
TI  - TCR beta feedback signals inhibit the coupling of recombinationally accessible V
      beta 14 segments with DJ beta complexes.
AB  - Ag receptor allelic exclusion is thought to occur through monoallelic initiation
      and subsequent feedback inhibition of recombinational accessibility. However, our
      previous analysis of mice containing a V(D)J recombination reporter inserted into
      Vbeta14 (Vbeta14(Rep)) indicated that Vbeta14 chromatin accessibility is
      biallelic. To determine whether Vbeta14 recombinational accessibility is subject
      to feedback inhibition, we analyzed TCRbeta rearrangements in Vbeta14(Rep) mice
      containing a preassembled in-frame transgenic Vbeta8.2Dbeta1Jbeta1.1 or an
      endogenous Vbeta14Dbeta1Jbeta1.4 rearrangement on the homologous chromosome.
      Expression of either preassembled VbetaDJbetaC beta-chain accelerated thymocyte
      development because of enhanced cellular selection, demonstrating that the rate
      limiting step in early alphabeta T cell development is the assembly of an in
      frame VbetaDJbeta rearrangement. Expression of these preassembled VbetaDJbeta
      rearrangements inhibited endogenous Vbeta14-to-DJbeta rearrangements as expected.
      However, in contrast to results predicted by the accepted model of TCRbeta
      feedback inhibition, we found that expression of these preassembled TCR beta
      chains did not downregulate recombinational accessibility of Vbeta14 chromatin.
      Our findings suggest that TCRbeta-mediated feedback inhibition of Vbeta14
      rearrangements depends on inherent properties of Vbeta14, Dbeta, and Jbeta
      recombination signal sequences.

PMID- 20042592
TI  - IL-17 regulates CXCL1 mRNA stability via an AUUUA/tristetraprolin-independent
      sequence.
AB  - IL-17 contributes to inflammatory response in part by promoting enhanced
      expression of chemokines, such as CXCL1, by prolonging the t(1/2) of this
      constitutively unstable mRNA. Although IL-17 is a weak stimulus for transcription
      of the CXCL1 gene, it strongly potentiates message accumulation via stabilization
      when the mRNA is transcribed in cells stimulated with TNF. In myeloid cells, LPS
      induced CXCL1 mRNA stabilization is dependent on AUUUA-containing sequence motifs
      that are recognized by the RNA binding protein tristetraprolin (TTP). Using
      deletion and site-specific mutagenesis, we report that IL-17-mediated
      stabilization of CXCL1 mRNA in nonmyeloid cells depends on a sequence that does
      not contain the AUUUA motif. Furthermore, a specific two-nucleotide mutation
      within this region markedly abrogates sensitivity for IL-17-mediated
      stabilization. Consistent with this finding, the IL-17-sensitive sequence does
      not exhibit increased instability in the presence of TTP, and CXCL1 mRNA remains
      unstable and can be stabilized in response to treatment with IL-17 in embryo
      fibroblasts from mice in which the TTP gene has been deleted. Whereas the RNA
      binding protein KSRP has been shown to participate in regulating the instability
      of human CXCL8 mRNA, inhibitory RNA-based reduction in KSRP does not effect the
      instability mediated by the IL-17-sensitive sequence motif. These findings
      suggest that IL-17-mediated chemokine mRNA stabilization in nonmyeloid cells uses
      a mechanism that is distinct from that operating to control AU-rich mRNA
      stability in myeloid cells.

PMID- 20042593
TI  - Cell type-specific recognition of human metapneumoviruses (HMPVs) by retinoic
      acid-inducible gene I (RIG-I) and TLR7 and viral interference of RIG-I ligand
      recognition by HMPV-B1 phosphoprotein.
AB  - Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that
      contribute to respiratory tract infections in children. No effective treatments
      or vaccines are available. Successful defense against virus infection relies on
      early detection by germ line-encoded pattern recognition receptors and activation
      of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid
      inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we
      investigated the abilities of two prototype strains of HMPV (A1 [NL?1?00] and B1
      [NL?1?99]) to activate RIG-I and induce type I IFNs. Despite the abilities of
      both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells,
      only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The
      failure of the HMPV-B1 strain to elicit type I IFN production was dependent on
      the B1 phosphoprotein, which specifically prevented RIG-I-mediated sensing of
      HMPV viral 5' triphosphate RNA. In contrast to most cell types, plasmacytoid
      dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and
      in this case sensing was via TLR7 rather than RIG-I. Collectively, these data
      reveal differential mechanisms of sensing for two closely related viruses, which
      operate in cell type-specific manners.

PMID- 20042594
TI  - Covalent bond between ligand and receptor required for efficient activation in
      rhodopsin.
AB  - Rhodopsin is an extensively studied member of the G protein-coupled receptors
      (GPCRs). Although rhodopsin shares many features with the other GPCRs, it
      exhibits unique features as a photoreceptor molecule. A hallmark in the molecular
      structure of rhodopsin is the covalently bound chromophore that regulates the
      activity of the receptor acting as an agonist or inverse agonist. Here we show
      the pivotal role of the covalent bond between the retinal chromophore and the
      lysine residue at position 296 in the activation pathway of bovine rhodopsin, by
      use of a rhodopsin mutant K296G reconstituted with retinylidene Schiff bases. Our
      results show that photoreceptive functions of rhodopsin, such as regiospecific
      photoisomerization of the ligand, and its quantum yield were not affected by the
      absence of the covalent bond, whereas the activation mechanism triggered by
      photoisomerization of the retinal was severely affected. Furthermore, our results
      show that an active state similar to the Meta-II intermediate of wild-type
      rhodopsin did not form in the bleaching process of this mutant, although it
      exhibited relatively weak G protein activity after light irradiation because of
      an increased basal activity of the receptor. We propose that the covalent bond is
      required for transmitting structural changes from the photoisomerized agonist to
      the receptor and that the covalent bond forcibly keeps the low affinity agonist
      in the receptor, resulting in a more efficient G protein activation.

PMID- 20042595
TI  - Differentiation of embryonic stem cells 1 (Dies1) is a component of bone
      morphogenetic protein 4 (BMP4) signaling pathway required for proper
      differentiation of mouse embryonic stem cells.
AB  - Embryonic stem cells (ESCs) are pluripotent cells able to grow indefinitely in
      culture and to differentiate into all cell types of embryos upon specific
      stimuli. Molecular mechanisms controlling the unique characteristics of ESCs are
      still largely unknown. We identified Dies1 (Differentiation of ESCs 1), an
      unpublished gene, that encodes a type I membrane protein. ESCs stably transfected
      with Dies1 small hairpin RNAs failed to properly differentiate toward neural and
      cardiac cell fate upon appropriate stimuli and continued to express markers of
      undifferentiated cells, such as the membrane-associated alkaline phosphatase, and
      transcription factors, like Oct3/4 and Nanog, when grown under conditions
      promoting differentiation. Our results demonstrated that Dies1 is required for
      BMP4/Smad1 signaling cascade; in undifferentiated ESCs Dies1 knockdown did not
      affect the expression of leukemia inhibitory factor downstream targets, whereas
      it resulted in a strong decrease of BMP4 signaling, as demonstrated by the
      decrease of Id1, -2, and -3 mRNAs, the decreased activity of Id1 gene promoter,
      and the reduced phospho-Smad1 levels. Dies1 knockdown had no effect in murine
      ESCs when the expression of the BMP4 receptor Alk3 was suppressed. The phenotype
      induced by Dies1 suppression in ESCs is due to the indirect activation of the
      Nodal/Activin pathway, which is a consequence of the BMP4 pathway inhibition and
      is sufficient to support the mESC undifferentiated state in the absence of
      leukemia inhibitory factor.

PMID- 20042596
TI  - Structural basis for the association of the redox-sensitive target of rapamycin
      FATC domain with membrane-mimetic micelles.
AB  - The target of rapamycin (TOR) is a conserved eukaryotic Ser/Thr kinase that
      regulates cellular growth in response to the nutrient and energy state. TOR
      signaling plays an important role in the development of diseases such as cancer,
      obesity, and diabetes and in different redox-sensitive processes (hypoxia,
      apoptosis, and aging). Because TOR has been detected at different cellular
      membranes and in the nucleus, its localization may influence the specific
      signaling readout. To better understand how TOR can associate with different
      membranes, the lipid-binding properties of the redox-sensitive yeast TOR1 FATC
      domain (y1fatc) have been characterized by solution NMR spectroscopy. Binding
      studies with different lipids indicate that y1fatc interacts specifically with a
      membrane-mimetic environment but appears not to recognize a specific lipid
      headgroup. In both, the structures of oxidized and reduced micelle-bound y1fatc,
      residues Ile-2456 to Trp-2470 of the lipid-binding motif form a hydrophobic bulb
      that has a rim of charged residues. The diffusion constants for both micelle
      bound states are consistent with the rotational correlation times from the
      analysis of the (15)N relaxation data. Based on the K(d) values, the oxidized
      form (K(d) approximately 0.31 mm) binds dodecyl phosphocholine micelles slightly
      tighter than the reduced form (K(d) approximately 1.86 mM). Binding studies with
      y1fatc in which one or both tryptophans (Trp-2466 and Trp-2470) were replaced by
      alanine suggest that these residues are important for the exact positioning in
      the membrane and that the other aromatic (His-2462, Tyr-2463, and Phe-2469) and
      aliphatic residues (Ile-2456, Leu-2459, Ile-2464, and Pro-2468) in the lipid
      binding motif contribute significantly to the affinity.

PMID- 20042597
TI  - Identification and functional characterization of the first nucleobase
      transporter in mammals: implication in the species difference in the intestinal
      absorption mechanism of nucleobases and their analogs between higher primates and
      other mammals.
AB  - Nucleobases are important compounds that constitute nucleosides and nucleic
      acids. Although it has long been suggested that specific transporters are
      involved in their intestinal absorption and uptake in other tissues, none of
      their molecular entities have been identified in mammals to date. Here we
      describe identification of rat Slc23a4 as the first sodium-dependent nucleobase
      transporter (rSNBT1). The mRNA of rSNBT1 was expressed highly and only in the
      small intestine. When transiently expressed in HEK293 cells, rSNBT1 could
      transport uracil most efficiently. The transport of uracil mediated by rSNBT1 was
      sodium-dependent and saturable with a Michaelis constant of 21.2 microM. Thymine,
      guanine, hypoxanthine, and xanthine were also transported, but adenine was not.
      It was also suggested by studies of the inhibitory effect on rSNBT1-mediated
      uracil transport that several nucleobase analogs such as 5-fluorouracil are
      recognized by rSNBT1, but cytosine and nucleosides are not or only poorly
      recognized. Furthermore, rSNBT1 fused with green fluorescent protein was mainly
      localized at the apical membrane, when stably expressed in polarized Madin-Darby
      canine kidney II cells. These characteristics of rSNBT1 were almost fully in
      agreement with those of the carrier-mediated transport system involved in
      intestinal uracil uptake. Therefore, it is likely that rSNBT1 is its molecular
      entity or at least in part responsible for that. It was also found that the gene
      orthologous to the rSNBT1 gene is genetically defective in humans. This may have
      a biological and evolutional meaning in the transport and metabolism of
      nucleobases. The present study provides novel insights into the specific
      transport and metabolism of nucleobases and their analogs for therapeutic use.

PMID- 20042598
TI  - Characterization and structural studies of the Plasmodium falciparum ubiquitin
      and Nedd8 hydrolase UCHL3.
AB  - Like their human hosts, Plasmodium falciparum parasites rely on the ubiquitin
      proteasome system for survival. We previously identified PfUCHL3, a
      deubiquitinating enzyme, and here we characterize its activity and changes in
      active site architecture upon binding to ubiquitin. We find strong evidence that
      PfUCHL3 is essential to parasite survival. The crystal structures of both PfUCHL3
      alone and in complex with the ubiquitin-based suicide substrate UbVME suggest a
      rather rigid active site crossover loop that likely plays a role in restricting
      the size of ubiquitin adduct substrates. Molecular dynamics simulations of the
      structures and a model of the PfUCHL3-PfNedd8 complex allowed the identification
      of shared key interactions of ubiquitin and PfNedd8 with PfUCHL3, explaining the
      dual specificity of this enzyme. Distinct differences observed in ubiquitin
      binding between PfUCHL3 and its human counterpart make it likely that the
      parasitic DUB can be selectively targeted while leaving the human enzyme
      unaffected.

PMID- 20042599
TI  - Filling the gap, evolutionarily conserved Omp85 in plastids of chromalveolates.
AB  - Chromalveolates are a diverse group of protists that include many ecologically
      and medically relevant organisms such as diatoms and apicomplexan parasites. They
      possess plastids generally surrounded by four membranes, which evolved by
      engulfment of a red alga. Today, most plastid proteins must be imported, but many
      aspects of protein import into complex plastids are still cryptic. In particular,
      how proteins cross the third outermost membrane has remained unexplained. We
      identified a protein in the third outermost membrane of the diatom Phaeodactylum
      tricornutum with properties comparable to those of the Omp85 family. We
      demonstrate that the targeting route of P. tricornutum Omp85 parallels that of
      the translocation channel of the outer envelope membrane of chloroplasts, Toc75.
      In addition, the electrophysiological properties are similar to those of the
      Omp85 proteins involved in protein translocation. This supports the hypothesis
      that P. tricornutum Omp85 is involved in precursor protein translocation, which
      would close a gap in the fundamental understanding of the evolutionary origin and
      function of protein import in secondary plastids.

PMID- 20042600
TI  - Site-directed mutagenesis of apolipoprotein CII to probe the role of its
      secondary structure for activation of lipoprotein lipase.
AB  - Apolipoprotein CII (apoCII) is a necessary activator for lipoprotein lipase
      (LPL). We had identified four residues (Tyr-63, Ile-66, Asp-69, and Gln-70),
      presumably contained in an alpha-helix, as a potential binding site for LPL. We
      have now used structure prediction, mutagenesis, and functional assays to explore
      the functional role of the secondary structure in this part of apoCII. First,
      mutants were generated by replacements with proline residues to disturb the
      helical structure. Activation by mutant G65P was reduced by 30%, whereas mutant
      S54P retained activation ability. Mutants V71P and L72P should be located outside
      the LPL-binding site, but V71P was totally inactive, whereas activation by L72P
      was reduced by 65%. Insertion of alanine after Tyr-63, changing the position of
      the putative LPL-binding site in relation to the hydrophobic face of the alpha
      helix, also severely impeded the activation ability, and a double mutant
      (Y63A/I66A) was completely inactive. Next, to investigate the importance of
      conserved hydrophobic residues in the C-terminal end of apoCII, Phe-67, Val-71,
      Leu-72, and Leu-75 were exchanged for polar residues. Only F67S showed dramatic
      loss of function. Finally, fragment 39-62, previously claimed to activate LPL,
      was found to be completely inactive. Our data support the view that the helical
      structure close to the C-terminal end of apoCII is important for activation of
      LPL, probably by placing residues 63, 66, 69, and 70 in an optimal steric
      position. The structural requirements for the hydrophobic face on the back side
      of this helix and further out toward the C terminus were less stringent.

PMID- 20042601
TI  - Nickel ions inhibit histone demethylase JMJD1A and DNA repair enzyme ABH2 by
      replacing the ferrous iron in the catalytic centers.
AB  - Iron- and 2-oxoglutarate-dependent dioxygenases are a diverse family of non-heme
      iron enzymes that catalyze various important oxidations in cells. A key
      structural motif of these dioxygenases is a facial triad of 2-histidines-1
      carboxylate that coordinates the Fe(II) at the catalytic site. Using histone
      demethylase JMJD1A and DNA repair enzyme ABH2 as examples, we show that this
      family of dioxygenases is highly sensitive to inhibition by carcinogenic nickel
      ions. We find that, with iron, the 50% inhibitory concentrations of nickel
      (IC(50) [Ni(II)]) are 25 microm for JMJD1A and 7.5 microm for ABH2. Without iron,
      JMJD1A is 10 times more sensitive to nickel inhibition with an IC(50) [Ni(II)] of
      2.5 microm, and approximately one molecule of Ni(II) inhibits one molecule of
      JMJD1A, suggesting that nickel causes inhibition by replacing the iron.
      Furthermore, nickel-bound JMJD1A is not reactivated by excessive iron even up to
      a 2 mm concentration. Using x-ray absorption spectroscopy, we demonstrate that
      nickel binds to the same site in ABH2 as iron, and replacement of the iron by
      nickel does not prevent the binding of the cofactor 2-oxoglutarate. Finally, we
      show that nickel ions target and inhibit JMJD1A in intact cells, and disruption
      of the iron-binding site decreases binding of nickel ions to ABH2 in intact
      cells. Together, our results reveal that the members of this dioxygenase family
      are specific targets for nickel ions in cells. Inhibition of these dioxygenases
      by nickel is likely to have widespread impacts on cells (e.g. impaired epigenetic
      programs and DNA repair) and may eventually lead to cancer development.

PMID- 20042602
TI  - The middle region of an HP1-binding protein, HP1-BP74, associates with linker DNA
      at the entry/exit site of nucleosomal DNA.
AB  - In higher eukaryotic cells, DNA molecules are present as chromatin fibers,
      complexes of DNA with various types of proteins; chromatin fibers are highly
      condensed in metaphase chromosomes during mitosis. Although the formation of the
      metaphase chromosome structure is essential for the equal segregation of
      replicated chromosomal DNA into the daughter cells, the mechanism involved in the
      organization of metaphase chromosomes is poorly understood. To identify proteins
      involved in the formation and/or maintenance of metaphase chromosomes, we
      examined proteins that dissociated from isolated human metaphase chromosomes by
      0.4 m NaCl treatment; this treatment led to significant chromosome
      decondensation, but the structure retained the core histones. One of the proteins
      identified, HP1-BP74 (heterochromatin protein 1-binding protein 74), composed of
      553 amino acid residues, was further characterized. HP1-BP74 middle region
      (BP74Md), composed of 178 amino acid residues (Lys(97)-Lys(274)), formed a
      chromatosome-like structure with reconstituted mononucleosomes and protected the
      linker DNA from micrococcal nuclease digestion by approximately 25 bp. The
      solution structure determined by NMR revealed that the globular domain (Met(153)
      Thr(237)) located within BP74Md possesses a structure similar to that of the
      globular domain of linker histones, which underlies its nucleosome binding
      properties. Moreover, we confirmed that BP74Md and full-length HP1-BP74 directly
      binds to HP1 (heterochromatin protein 1) and identified the exact sites
      responsible for this interaction. Thus, we discovered that HP1-BP74 directly
      binds to HP1, and its middle region associates with linker DNA at the entry/exit
      site of nucleosomal DNA in vitro.

PMID- 20042603
TI  - Toxoplasma gondii actin depolymerizing factor acts primarily to sequester G
      actin.
AB  - Toxoplasma gondii is a protozoan parasite belonging to the phylum Apicomplexa.
      Parasites in this phylum utilize a unique process of motility termed gliding,
      which is dependent on parasite actin filaments. Surprisingly, 98% of parasite
      actin is maintained as G-actin, suggesting that filaments are rapidly assembled
      and turned over. Little is known about the regulated disassembly of filaments in
      the Apicomplexa. In higher eukaryotes, the related actin depolymerizing factor
      (ADF) and cofilin proteins are essential regulators of actin filament turnover.
      ADF is one of the few actin-binding proteins conserved in apicomplexan parasites.
      In this study we examined the mechanism by which T. gondii ADF (TgADF) regulates
      actin filament turnover. Unlike other members of the ADF/cofilin (AC) family,
      apicomplexan ADFs lack key F-actin binding sites. Surprisingly, this promotes
      their enhanced disassembly of actin filaments. Restoration of the C-terminal F
      actin binding site to TgADF stabilized its interaction with filaments but reduced
      its net filament disassembly activity. Analysis of severing activity revealed
      that TgADF is a weak severing protein, requiring much higher concentrations than
      typical AC proteins. Investigation of TgADF interaction with T. gondii actin
      (TgACT) revealed that TgADF disassembled short TgACT oligomers. Kinetic and
      steady-state polymerization assays demonstrated that TgADF has strong monomer
      sequestering activity, inhibiting TgACT polymerization at very low
      concentrations. Collectively these data indicate that TgADF promoted the
      efficient turnover of actin filaments via weak severing of filaments and strong
      sequestering of monomers. This suggests a dual role for TgADF in maintaining high
      G-actin concentrations and effecting rapid filament turnover.

PMID- 20042604
TI  - A conformational switch in the scaffolding protein NHERF1 controls autoinhibition
      and complex formation.
AB  - The mammalian Na(+)/H(+) exchange regulatory factor 1 (NHERF1) is a multidomain
      scaffolding protein essential for regulating the intracellular trafficking and
      macromolecular assembly of transmembrane ion channels and receptors. NHERF1
      consists of tandem PDZ-1, PDZ-2 domains that interact with the cytoplasmic
      domains of membrane proteins and a C-terminal (CT) domain that binds the membrane
      cytoskeleton linker protein ezrin. NHERF1 is held in an autoinhibited state
      through intramolecular interactions between PDZ2 and the CT domain that also
      includes a C-terminal PDZ-binding motif (-SNL). We have determined the structures
      of the isolated and tandem PDZ2CT domains by high resolution NMR using small
      angle x-ray scattering as constraints. The PDZ2CT structure shows weak
      intramolecular interactions between the largely disordered CT domain and the PDZ
      ligand binding site. The structure reveals a novel helix-turn-helix subdomain
      that is allosterically coupled to the putative PDZ2 domain by a network of
      hydrophobic interactions. This helical subdomain increases both the stability and
      the binding affinity of the extended PDZ structure. Using NMR and small angle
      neutron scattering for joint structure refinement, we demonstrate the release of
      intramolecular domain-domain interactions in PDZ2CT upon binding to ezrin. Based
      on the structural information, we show that human disease-causing mutations in
      PDZ2, R153Q and E225K, have significantly reduced protein stability. Loss of
      NHERF1 expressed in cells could result in failure to assemble membrane complexes
      that are important for normal physiological functions.

PMID- 20042605
TI  - Basis for the isoform-specific interaction of myosin phosphatase subunits protein
      phosphatase 1c beta and myosin phosphatase targeting subunit 1.
AB  - Myosin II association with actin, which triggers contraction, is regulated by
      orchestrated waves of phosphorylation/dephosphorylation of the myosin regulatory
      light chain. Blocking myosin regulatory light chain phosphorylation with small
      molecule inhibitors alters the shape, adhesion, and migration of many types of
      smooth muscle and cancer cells. Dephosphorylation is mediated by myosin
      phosphatase (MP), a complex that consists of a catalytic subunit (protein
      phosphatase 1c, PP1c), a large subunit (myosin phosphatase targeting subunit,
      MYPT), and a small subunit of unknown function. MYPT functions by targeting PP1c
      onto its substrate, phosphorylated myosin II. Using RNA interference, we show
      here that stability of PP1c beta and MYPT1 is interdependent; knocking down one
      of the subunits decreases the expression level of the other. Associated changes
      in cell shape also occur, characterized by flattening and spreading accompanied
      by increased cortical actin, and cell numbers decrease secondary to apoptosis. Of
      the three highly conserved isoforms of PP1c, we show that MYPT1 binding is
      restricted to PP1c beta, and, using chimeric analysis and site-directed
      mutations, that the central region of PP1c beta confers the isoform-specific
      binding. This finding was unexpected because the MP crystal structure has been
      solved and was reported to identify the variable, C-terminal domain of PP1c beta
      as being the region key for isoform-specific interaction with MYPT1. These
      findings suggest a potential screening strategy for cardiovascular and cancer
      therapeutic agents based on destabilizing MP complex formation and function.

PMID- 20042606
TI  - Platelet-derived growth factor differentially regulates the expression and post
      translational modification of versican by arterial smooth muscle cells through
      distinct protein kinase C and extracellular signal-regulated kinase pathways.
AB  - The synthesis of proteoglycans involves steps that regulate both protein and
      glycosaminoglycan (GAG) synthesis, but it is unclear whether these two pathways
      are regulated by the same or different signaling pathways. We therefore
      investigated signaling pathways involved in platelet-derived growth factor (PDGF)
      mediated increases in versican core protein and GAG chain synthesis in arterial
      smooth muscle cells (ASMCs). PDGF treatment of ASMCs resulted in increased
      versican core protein synthesis and elongation of GAG chains attached to the
      versican core protein. The effects of PDGF on versican mRNA were blocked by
      inhibiting either protein kinase C (PKC) or the ERK pathways, whereas the GAG
      elongation effect of PDGF was blocked by PKC inhibition but not by ERK
      inhibition. Interestingly, blocking protein synthesis in the presence of
      cycloheximide abolished the PDGF effect, but not in the presence of xyloside,
      indicating that GAG synthesis that results from PKC activation is independent
      from de novo protein synthesis. PDGF also stimulated an increase in the
      chondroitin-6-sulfate to chondroitin-4-sulfate ratio of GAG chains on versican,
      and this effect was blocked by PKC inhibitors. These data show that PKC
      activation is sufficient to cause GAG chain elongation, but both PKC and ERK
      activation are required for versican mRNA core protein expression. These results
      indicate that different signaling pathways control different aspects of PDGF
      stimulated versican biosynthesis by ASMCs. These data will be useful in designing
      strategies to interfere with the synthesis of this proteoglycan in various
      disease states.

PMID- 20042607
TI  - SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase
      2 expression in macrophages.
AB  - SIRT1 (Sirtuin type 1), a mammalian orthologue of yeast SIR2 (silent information
      regulator 2), has been shown to mediate a variety of calorie restriction (CR)
      induced physiological events, such as cell fate regulation via deacetylation of
      the substrate proteins. However, whether SIRT1 deacetylates activator protein-1
      (AP-1) to influence its transcriptional activity and target gene expression is
      still unknown. Here we demonstrate that SIRT1 directly interacts with the basic
      leucine zipper domains of c-Fos and c-Jun, the major components of AP-1, by which
      SIRT1 suppressed the transcriptional activity of AP-1. This process requires the
      deacetylase activity of SIRT1. Notably, SIRT1 reduced the expression of COX-2, a
      typical AP-1 target gene, and decreased prostaglandin E(2) (PGE(2)) production of
      peritoneal macrophages (pMPhis). pMPhis with SIRT1 overexpression displayed
      improved phagocytosis and tumoricidal functions, which are associated with
      depressed PGE(2). Furthermore, SIRT1 protein level was up-regulated in CR mouse
      pMPhis, whereas elevated SIRT1 decreased COX-2 expression and improved PGE(2)
      related macrophage functions that were reversed following inhibition of SIRT1
      deacetylase activity. Thus, our results indicate that SIRT1 may be a mediator of
      CR-induced macrophage regulation, and its deacetylase activity contributes to the
      inhibition of AP-1 transcriptional activity and COX-2 expression leading to
      amelioration of macrophage function.

PMID- 20042608
TI  - Receptor interacting protein 3 suppresses vascular smooth muscle cell growth by
      inhibition of the phosphoinositide 3-kinase-Akt axis.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) is a primary mechanism
      underlying cardiovascular proliferative disorders. Phosphoinositide 3-kinase
      (PI3K)-Akt (or protein kinase B) axis has been assigned at the center of pathways
      that regulate cell proliferation. Here we demonstrate that enhanced PI3K-Akt
      signaling by mitogenic stimulation or arterial injury profoundly elevates
      expression of receptor interacting protein 3 (RIP3) in primary cultured rat VSMCs
      and in vivo and that the up-regulation of RIP3 leads to VSMC growth arrest and
      apoptosis via inhibiting the PI3K-Akt signaling pathway, thereby alleviating
      balloon injury-induced neointimal formation. Specifically, mitogenic stimulation
      with platelet-derived growth factor-BB or angiotensin II leads to a profound
      increase in RIP3 expression, which is abolished by inhibition of PI3K or Akt, and
      increased PI3K-Akt signaling by expression of a constitutively active PI3K mutant
      also elevates RIP3 expression. Importantly, adenoviral overexpression of RIP3 not
      only triggers apoptosis but also causes cell cycle arrest at G(1)/G(0) phases
      that is associated with suppressed Akt activation. In sharp contrast, RIP3 gene
      silencing enhances serum- and platelet-derived growth factor-induced cell
      proliferation and Akt activation. In vivo adenoviral gene delivery of rat RIP3
      (rRIP3) increased apoptosis and reduced VSMC proliferation, thus, effectively
      alleviating balloon injury-induced neointimal formation. The growth-suppressive
      and pro-apoptotic effects are independent of rRIP3 Ser/Thr kinase activity,
      because overexpression of a kinase-inactive mutant of rRIP3, similar to its wild
      type, is sufficient to induce growth arrest and apoptosis. These findings reveal
      a novel growth-suppressive action of RIP3, marking RIP3 as an important factor to
      prevent excessive mitogenic stimulation- or injury-induced vascular smooth muscle
      cells hyperplasia.

PMID- 20042609
TI  - Mechano-transduction in osteoblastic cells involves strain-regulated estrogen
      receptor alpha-mediated control of insulin-like growth factor (IGF) I receptor
      sensitivity to Ambient IGF, leading to phosphatidylinositol 3-kinase/AKT
      dependent Wnt/LRP5 receptor-independent activation of beta-catenin signaling.
AB  - The capacity of bones to adjust their mass and architecture to withstand the
      loads of everyday activity derives from the ability of their resident cells to
      respond appropriately to the strains engendered. To elucidate the mechanisms of
      strain responsiveness in bone cells, we investigated in vitro the responses of
      primary mouse osteoblasts and UMR-106 osteoblast-like cells to a single period of
      dynamic strain. This stimulates a cascade of events, including activation of
      insulin-like growth factor I receptor (IGF-IR), phosphatidylinositol 3-kinase
      mediated phosphorylation of AKT, inhibition of GSK-3beta, increased activation of
      beta-catenin, and associated lymphoid-enhancing factor/T cell factor-mediated
      transcription. Initiation of this pathway does not involve the Wnt/LRP5/Frizzled
      receptor and does not culminate in increased IGF transcription. The effect of
      strain on IGF-IR is mimicked by exogenous des-(1-3)IGF-I and is blocked by the
      IGF-IR inhibitor H1356. Inhibition of strain-related prostanoid and nitric oxide
      production inhibits strain-related (and basal) AKT activity, but their separate
      ectopic administration does not mimic it. Strain-related IGF-IR activation of AKT
      requires estrogen receptor alpha (ERalpha) with which IGF-1R physically
      associates. The ER blocker ICI 182,780 increases the concentration of des-(1
      3)IGF-I necessary to activate this cascade, whereas estrogen inhibits both basal
      AKT activity and its activation by des-(1-3)IGF-I. These data suggest an initial
      cascade of strain-related events in osteoblasts in which strain activates IGF-IR,
      in association with ERalpha, so initiating phosphatidylinositol 3-kinase/AKT
      dependent activation of beta-catenin and altered lymphoid-enhancing factor/T cell
      factor transcription. This cascade requires prostanoid/nitric oxide production
      and is independent of Wnt/LRP5.

PMID- 20042610
TI  - TbPIF1, a Trypanosoma brucei mitochondrial DNA helicase, is essential for
      kinetoplast minicircle replication.
AB  - Kinetoplast DNA, the trypanosome mitochondrial genome, is a network of
      interlocked DNA rings including several thousand minicircles and a few dozen
      maxicircles. Minicircles replicate after release from the network, and their
      progeny reattach. Remarkably, trypanosomes have six mitochondrial DNA helicases
      related to yeast PIF1 helicase. Here we report that one of the six, TbPIF1,
      functions in minicircle replication. RNA interference (RNAi) of TbPIF1 causes a
      growth defect and kinetoplast DNA loss. Minicircle replication intermediates
      decrease during RNAi, and there is an accumulation of multiply interlocked,
      covalently closed minicircle dimers (fraction U). In studying the significance of
      fraction U, we found that this species also accumulates during RNAi of
      mitochondrial topoisomerase II. These data indicate that one function of TbPIF1
      is an involvement, together with topoisomerase II, in the segregation of
      minicircle progeny.

PMID- 20042611
TI  - The C-terminal repeat domain of Spt5 plays an important role in suppression of
      Rad26-independent transcription coupled repair.
AB  - In eukaryotic cells, transcription coupled nucleotide excision repair (TCR) is
      believed to be initiated by RNA polymerase II (Pol II) stalled at a lesion in the
      transcribed strand of a gene. Rad26, the yeast homolog of the human Cockayne
      syndrome group B (CSB) protein, plays an important role in TCR. Spt4, a
      transcription elongation factor that forms a complex with Spt5, has been shown to
      suppress TCR in rad26Delta cells. Here we present evidence that Spt4 indirectly
      suppresses Rad26-independent TCR by protecting Spt5 from degradation and
      stabilizing the interaction of Spt5 with Pol II. We further found that the C
      terminal repeat (CTR) domain of Spt5, which is dispensable for cell viability and
      is not involved in interactions with Spt4 and Pol II, plays an important role in
      the suppression. The Spt5 CTR is phosphorylated by the Bur kinase. Inactivation
      of the Bur kinase partially alleviates TCR in rad26Delta cells. We propose that
      the Spt5 CTR suppresses Rad26-independent TCR by serving as a platform for
      assembly of a multiple protein suppressor complex that is associated with Pol II.
      Phosphorylation of the Spt5 CTR by the Bur kinase may facilitate the assembly of
      the suppressor complex.

PMID- 20042612
TI  - NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by
      deacetylation of the ribosomal protein MRPL10.
AB  - A member of the sirtuin family of NAD(+)-dependent deacetylases, SIRT3, is
      located in mammalian mitochondria and is important for regulation of
      mitochondrial metabolism, cell survival, and longevity. In this study, MRPL10
      (mitochondrial ribosomal protein L10) was identified as the major acetylated
      protein in the mitochondrial ribosome. Ribosome-associated SIRT3 was found to be
      responsible for deacetylation of MRPL10 in an NAD(+)-dependent manner. We mapped
      the acetylated Lys residues by tandem mass spectrometry and determined the role
      of these residues in acetylation of MRPL10 by site-directed mutagenesis.
      Furthermore, we observed that the increased acetylation of MRPL10 led to an
      increase in translational activity of mitochondrial ribosomes in Sirt3(-/-) mice.
      In a similar manner, ectopic expression and knockdown of SIRT3 in C2C12 cells
      resulted in the suppression and enhancement of mitochondrial protein synthesis,
      respectively. Our findings constitute the first evidence for the regulation of
      mitochondrial protein synthesis by the reversible acetylation of the
      mitochondrial ribosome and characterize MRPL10 as a novel substrate of the NAD(+)
      dependent deacetylase, SIRT3.

PMID- 20042613
TI  - StarD7 mediates the intracellular trafficking of phosphatidylcholine to
      mitochondria.
AB  - Steroidogenic acute regulatory protein-related lipid transfer (START) domains,
      found in 15 mammalian proteins termed StarD1-StarD15, are lipid-binding domains
      implicated in the intracellular lipid transport systems. In the present study, we
      analyzed the lipid ligand and function of StarD7. We found two variable forms of
      mammalian StarD7, termed StarD7-I and StarD7-II. Unlike StarD7-II, StarD7-I
      contained a mitochondrial-targeting sequence in its N terminus. Overexpressed
      StarD7-I tagged with V5/His in HEPA-1 cells was mainly observed in the
      mitochondria of cells prepared at low cellular density, but it was distributed in
      the cytoplasm of high density cells. StarD7-II was constantly distributed in the
      cytoplasm at any cellular density. Endogenous StarD7 in HEPA-1 cells and rat
      liver was also distributed in both the cytoplasm and the mitochondria. A protease
      K protection assay indicated that the mitochondrial StarD7 was associated with
      the outer mitochondrial membrane. The purified recombinant StarD7 specifically
      catalyzed the transfer of PC between lipid vesicles in vitro. Furthermore, the
      intracellular transport of fluorescent PC that was exogenously incorporated into
      the mitochondria was increased in cells that overexpressed StarD7-I. These
      results suggest that StarD7 facilitates the delivery of PC to mitochondria in non
      vesicular system.

PMID- 20042614
TI  - Evaluation of a newly developed GenoArray human papillomavirus (HPV) genotyping
      assay and comparison with the Roche Linear Array HPV genotyping assay.
AB  - Persistent infection with high-risk types of human papillomavirus (HPV) is a
      necessary step in the development of cervical cancer. The incorporation of HPV
      detection into cervical screening programs may improve the ability to identify
      women at risk of cervical cancer. We recently evaluated the performance
      characteristics of a newly developed HPV detection assay, the GenoArray (GA)
      genotyping assay, for the detection of HPV infections by comparing it with the
      commercial Roche Linear Array (LA) HPV genotyping assay. The GA assay has an
      analytical sensitivity for the detection of HPV types 16 (HPV-16) and HPV-18 of
      as few as 10 to 50 copies, and its reproducibility is adequate. The GA and LA
      assays showed no significant difference in the rates of detection of genotypes
      detected by both HPV genotyping assays and oncogenic genotypes, and the
      interassay agreement was excellent. The GA and LA assays revealed either
      concordant or compatible genotyping results for 97.5% of the samples and
      discordant results for only eight (2.5%) samples. Compatible results were also
      observed for the detection of single or multiple HPV infections and the detection
      of most of the genotypes. The GA assay also demonstrated good clinical
      performance characteristics when the comparisons were carried out with clinical
      subgroups of samples from patients with normal cytologies, low-grade or high
      grade squamous intraepithelial lesions, and cancers. Therefore, the GA assay
      appears to be highly sensitive and specific for the genotyping of HPV. It has the
      advantage that it specifically detects HPV-52, which overcomes a limitation of
      the LA assay, and hence, it has potential value for use for genotyping,
      especially in regions where HPV-52 has a high prevalence.

PMID- 20042615
TI  - Application of truncated immunodominant polypeptide from hepatitis E virus (HEV)
      ORF2 in an assay to exclude nonspecific binding in detecting anti-HEV
      immunoglobulin M.
AB  - The diagnosis of recent hepatitis E virus (HEV) infection depends on serologic
      testing for anti-HEV IgM; however, false-positive results may occur. In the
      present study, we cloned the ORF2 fragment of genotype 4 HEV and demonstrated
      that a subregion covering amino acids 459 to 607 in ORF2 forms the immunodominant
      B-cell epitopes, as it does in genotype 1 viruses. Truncation of several residues
      from either the N or C terminus of the polypeptide abolished the reactivity of
      anti-HEV from naturally infected persons. By the combination of high reactivity
      of the immunodominant polypeptide and poor reactivity of the truncated
      polypeptide, we established an indirect enzyme-linked immunosorbent assay (ELISA)
      to detect anti-HEV IgM. In this assay, all 37 sera that were HEV RNA positive
      reacted with the immunodominant polypeptide but not with the truncated one, and
      none of 159 sera from healthy persons reacted with either of the polypeptides. In
      retesting of 117 sera that originally tested positive for anti-HEV IgM, using a
      Genelabs kit, only 34 were positive and 83 were negative. Western blot analyses
      and other experiments strongly indicated that these 83 discordant sera were
      negative for anti-HEV IgM. Furthermore, among the 117 sera, 5 reacted with both
      the immunodominant and truncated polypeptides, with comparable optical densities
      at 450 nm. However, their reactivity was demonstrated to result from nonspecific
      binding. Together, the data indicate that the poor reactivity of a truncated ORF2
      polypeptide can be used to exclude nonspecific binding in the detection of anti
      HEV IgM.

PMID- 20042616
TI  - Evidence of emergence of new GGII.4 norovirus variants from gastroenteritis
      outbreak survey in France during the 2007-to-2008 and 2008-to-2009 winter
      seasons.
AB  - Analysis of 316 outbreaks of gastroenteritis in France from September 2007
      through March 2009 showed that genogroup II.4 (GGII.4) noroviruses were
      predominant and mostly belonged to the 2006b variant. However, the new GGII.4
      variants, variant 2008 and the newly discovered Cairo variant from the Middle
      East, were also detected. The epidemiological survey suggests that these new
      variants might become the next predominant strains.

PMID- 20042617
TI  - Italian national survey of blood donors: external quality assessment (EQA) of
      syphilis testing.
AB  - The detection of syphilis among blood donors may reveal high-risk sexual
      behavior, which can go unreported at the time of donor selection and compromise
      the safety of the donated blood. In Italy, blood is collected, tested, and
      distributed by transfusion services (TSs), which also perform outpatient
      transfusions. Although the TSs must screen for syphilis by law, there are no
      indications of the specific type of method to be used, generating discrepancies
      in the results obtained by the different TSs. To determine the proficiency of the
      TSs in screening for syphilis, we performed an external quality assessment (EQA).
      The EQA was based on two shipments of serum panels; 133 and 118 of the 326
      existing TSs participated in the first and second shipments, respectively. Each
      panel consisted of both positive and negative serum samples. The results
      confirmed that the use of a single nontreponemal test (the Venereal Disease
      Research Laboratory [VDRL] and the rapid plasma reagin [RPR] tests) is the least
      sensitive means of identifying samples that are positive for syphilis antibodies.
      We also found that the interpretation of the results of manual techniques, such
      as the RPR test, the VDRL test, the Treponema pallidum hemagglutination (TPHA)
      assay, and the T. pallidum particle agglutination (TPPA) assay, can vary greatly
      among different TSs and operators. Total Ig enzyme immunoassays (EIAs) are the
      most sensitive. However, the determination of syphilis on the basis of the
      results of a single test is not sufficient for an accurate screening; and all
      blood units should thus be assessed by two distinct treponemal tests, that is, a
      total Ig EIA and the TPHA or the TPPA assay.

PMID- 20042618
TI  - Proof of principle for successful characterization of methicillin-resistant
      coagulase-negative staphylococci isolated from skin by use of Raman spectroscopy
      and pulsed-field gel electrophoresis.
AB  - Coagulase-negative staphylococci (CNS) are among the most frequently isolated
      bacterial species in clinical microbiology, and most CNS-related infections are
      hospital acquired. Distinguishing between these frequently multiple-antibiotic
      resistant isolates is important for both treatment and transmission control. In
      this study we used isolates of methicillin-resistant coagulase-negative
      staphylococci (MR-CNS) that were selected from a large surveillance study of the
      direct spread of MR-CNS. This strain collection was used to evaluate (i) Raman
      spectroscopy as a typing tool for MR-CNS isolates and (ii) diversity between
      colonies with identical and different morphologies. Reproducibility was high,
      with 215 of 216 (99.5%) of the replicate samples for 72 isolates ending up in the
      same cluster. The concordance with pulsed-field gel electrophoresis (PFGE)-based
      clusters was 94.4%. We also confirm that the skin of patients can be colonized
      with multiple MR-CNS types at the same time. Morphological differences between
      colonies from a single patient sample correlated with differences in Raman and
      PFGE types. Some morphologically indistinguishable colonies revealed different
      Raman and PFGE types. This indicates that multiple MR-CNS colonies should be
      examined to obtain a complete insight into the prevalence of different types and
      to be able to perform an accurate transmission analysis. Here we show that Raman
      spectroscopy is a reproducible typing system for MR-CNS isolates. It is a tool
      for screening variability within a collection of isolates. Because of the high
      throughput, it enables the analysis of multiple colonies per patient, which will
      enhance the quality of clinical and epidemiological studies.

PMID- 20042620
TI  - MIC quality control guidelines and disk diffusion test optimization for CEM-101,
      a novel fluoroketolide.
AB  - The development of diagnostic susceptibility tests for CEM-101, a new
      fluoroketolide, was addressed by structured studies to determine the optimal disk
      diffusion test concentration and effects of various testing conditions or
      supplements and to establish the quality control (QC) ranges for reference broth
      microdilution tests. The 15-microg CEM-101 disk was selected, and MIC ranges for
      a total of four QC organisms were proposed, with only three doubling dilutions
      each that included 95.6 to 99.7% of values reported from the eight-laboratory
      investigation.

PMID- 20042619
TI  - Clonal distribution of disease-associated and healthy carrier isolates of
      Neisseria meningitidis between 1983 and 2005 in Cuba.
AB  - In response to epidemic levels of serogroup B meningococcal disease in Cuba
      during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the
      National Infant Immunization Program in 1991. Since then the incidence of
      meningococcal disease in Cuba has returned to the low levels recorded before the
      epidemic. A total of 420 Neisseria meningitidis strains collected between 1983
      and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of
      strains comprised 167 isolated from disease cases and 253 obtained from healthy
      carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of
      these were reported to be a new ST. The Cuban isolates were associated with 12
      clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86
      isolates), and ST-41/44 (36 isolates). This study also showed that the
      application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the
      frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine
      serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages
      ST-8 and ST-11 were no longer found during the postvaccination period. 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- 20042621
TI  - Prevalence of the sodC gene in nontypeable Haemophilus influenzae and Haemophilus
      haemolyticus by microarray-based hybridization.
AB  - The sodC gene has been reported to be a useful marker for differentiating
      nontypeable (NT) Haemophilus influenzae from Haemophilus haemolyticus in
      respiratory-tract samples, but discrepancies exist as to the prevalence of sodC
      in NT H. influenzae. Therefore, we used a microarray-based, "library-on-a-slide"
      method to differentiate the species and found that 21 of 169 (12.4%) NT H.
      influenzae strains and all 110 (100%) H. haemolyticus strains possessed the sodC
      gene. Multilocus sequence analysis confirmed that the 21 NT H. influenzae strains
      were H. influenzae and not H. haemolyticus. An inactive sodC gene has been
      reported in encapsulated H. influenzae strains belonging to phylogenetic division
      II. Capsule-specific Southern hybridization and PCR and a lack of copper/zinc
      cofactored superoxide dismutase (CuZnSOD) expression indicated that 6 of the 21
      sodC-containing NT H. influenzae strains in our study were likely capsule
      deficient mutants belonging to phylogenetic division II. DNA sequence comparisons
      of the 21 H. influenzae sodC genes with sodC from H. haemolyticus or encapsulated
      H. influenzae demonstrated that the sodC genes of the six H. influenzae capsule
      deficient mutants were, on average, 99% identical to sodC from encapsulated H.
      influenzae but only 85% identical to sodC from H. haemolyticus. The sodC genes
      from 2/15 NT H. influenzae strains were similarly more closely related to sodC
      from encapsulated strains, while sodC genes from 13 NT H. influenzae strains were
      almost 95% identical to sodC genes from H. haemolyticus, suggesting the
      possibility of interspecies recombination in these strains. In summary, this
      study demonstrates that sodC is not completely absent (9.2%) in true NT H.
      influenzae strains.

PMID- 20042622
TI  - Comparison of the clinical performance of PapilloCheck human papillomavirus
      detection with that of the GP5+/6+-PCR-enzyme immunoassay in population-based
      cervical screening.
AB  - We compared the clinical performance of the PapilloCheck human papillomavirus
      (HPV) assay with that of the GP5+/6+-PCR method with an enzyme immunoassay
      readout (GP5+/6+-PCR-EIA) for the detection of high-risk HPV (hrHPV) types by the
      use of cervical samples originating from women in a population-based by the use
      of cervical screening cohort tested by combined cytology and GP5+/6+-PCR-EIA
      (POBASCAM trial). Specimens from a random sample of 1,437 controls (women ages 40
      to 60 years with normal cytological findings and without evidence of cervical
      intraepithelial neoplasia grade 2 or higher [> or = CIN2] within up to 8 years of
      follow-up) and 192 cases (women ages 30 to 60 years in whom > or = CIN3 was
      detected within up to 3 years of follow-up) were subjected to analysis by the
      PapilloCheck method. When all 17 (probably) hrHPV types were taken into account,
      the PapilloCheck assay had a clinical sensitivity for the detection of > or =
      CIN3 of 96.4% (185/192 samples; 95% confidence interval [CI], 93.7 to 99.7) and a
      clinical specificity for the detection of > or = CIN2 of 96.3% (95% CI, 95.3 to
      97.3). After restriction of the analysis by the PapilloCheck assay to the 14 hr
      HPV types targeted by GP5+/6+-PCR-EIA, the clinical sensitivity and clinical
      specificity values were 95.8% (95% CI, 92.8 to 98.8) and 96.7% (95% CI, 95.7 to
      97.7), respectively. By comparison, these values were 96.4% (95% CI, 93.9 to
      98.9) and 97.7% (95% CI, 96.9 to 98.5), respectively, for the GP5+/6+-PCR-EIA.
      When all 17 (probably) hrHPV types were included in the analysis, noninferiority
      score testing revealed that the clinical sensitivity of the PapilloCheck assay
      for the detection of > or = CIN3 was noninferior to that of the GP5+/6+-PCR-EIA
      (P < 0.0001), but the clinical specificity of the PapilloCheck assay for the
      detection of > or = CIN2 was inferior to that of the GP5+/6+-PCR-EIA (P = 0.08)
      when lower bounds of 90% for sensitivity and 98% for specificity were used. When
      the analysis was restricted to the 14 hrHPV types targeted by the GP5+/6+-PCR
      EIA, both the clinical sensitivity and the clinical specificity of the
      PapilloCheck assay were noninferior to those of the GP5+/6+-PCR-EIA
      (noninferiority score test; P < 0.0001 and P = 0.007, respectively). Thus, when
      the findings obtained for the 14 hrHPV types detectable by the GP5+/6+-PCR-EIA
      are considered, the PapilloCheck assay is clinically compatible with the GP5+/6+
      PCR-EIA.

PMID- 20042623
TI  - Multilocus sequence typing of Clostridium difficile.
AB  - A robust high-throughput multilocus sequence typing (MLST) scheme for Clostridium
      difficile was developed and validated using a diverse collection of 50 reference
      isolates representing 45 different PCR ribotypes and 102 isolates from recent
      clinical samples. A total of 49 PCR ribotypes were represented overall. All
      isolates were typed by MLST and yielded 40 sequence types (STs). A web-accessible
      database was set up (http://pubmlst.org/cdifficile/) to facilitate the
      dissemination and comparison of C. difficile MLST genotyping data among
      laboratories. MLST and PCR ribotyping were similar in discriminatory abilities,
      having indices of discrimination of 0.90 and 0.92, respectively. Some STs
      corresponded to a single PCR ribotype (32/40), other STs corresponded to multiple
      PCR ribotypes (8/40), and, conversely, the PCR ribotype was not always predictive
      of the ST. The total number of variable nucleotide sites in the concatenated MLST
      sequences was 103/3,501 (2.9%). Concatenated MLST sequences were used to
      construct a neighbor-joining tree which identified four phylogenetic groups of
      STs and one outlier (ST-11; PCR ribotype 078). These groups apparently correlate
      with clades identified previously by comparative genomics. The MLST scheme was
      sufficiently robust to allow direct genotyping of C. difficile in total stool DNA
      extracts without isolate culture. The direct (nonculture) MLST approach may prove
      useful as a rapid genotyping method, potentially benefiting individual patients
      and informing hospital infection control.

PMID- 20042624
TI  - Streptococcus pyogenes isolates causing severe infections in Norway in 2006 to
      2007: emm types, multilocus sequence types, and superantigen profiles.
AB  - To investigate the epidemiological patterns and genetic characteristics of
      disease caused by group A Streptococcus (GAS), all available isolates from
      invasive cases in Norway during 2006 to 2007 (262 isolates) were subjected to
      antimicrobial susceptibility testing, T serotyping, emm typing, and multilocus
      sequence typing and screened for known streptococcal pyrogenic exotoxin (Spe)
      genes, smeZ, and ssa. The average incidence rate was 3.1 cases per 100,000
      individuals. The most prevalent sequence types (STs) were STs 52, 28, and 334. In
      association with emm types 28, 77, and 87, the serotype T-28 comprised 24.8% of
      the strains. emm types 28, 1, and 82 were dominating. In 2007, a sharp increase
      in the number of emm-6 strains was noted. All strains were sensitive to
      penicillin and quinupristin-dalfopristin, while 3.4% and 6.1% of the strains were
      resistant to macrolides and tetracycline, respectively. Furthermore, the emm-6
      strains had intermediate susceptibility to ofloxacin. Isolates displayed a wide
      variety of gene profiles, as shown by the presence or absence of the Spe genes,
      smeZ, and ssa, but 48% of the isolates fell into one of three profiles. In most
      cases, an emm type was restricted to one gene profile. Although the incidence
      decreased during this study, invasive GAS disease still has a high endemic rate,
      with involvement of both established and emerging emm types displaying
      variability in virulence gene profiles as well as differences in gender and age
      group preferences.

PMID- 20042625
TI  - Emergence of SCCmec type IV and SCCmec type V methicillin-resistant
      Staphylococcus aureus containing the Panton-Valentine leukocidin genes in a large
      academic teaching hospital in central Switzerland: external invaders or
      persisting circulators?
AB  - The hospital epidemiology of methicillin-resistant Staphylococcus aureus (MRSA)
      has changed in the past few years due to the encroachment of community-associated
      MRSA (CA-MRSA) strains into health care settings. MRSA strains that were isolated
      during a 2-year period from patients of the Luzerner Kantonsspital were analyzed
      to elucidate their epidemiology. Moreover, extended surveillance of individuals
      who were contacts of those patients was carried out for 6 months to identify the
      routes of spread and to assess the quality of the infection control measures used
      in our setting. Patient data were collected to distinguish CA-MRSA strains from
      health care-associated MRSA (HA-MRSA) strains by epidemiological criteria, as
      defined by the Centers for Disease Control and Prevention (CDC). On the basis of
      the CDC definition, the majority of the strains were considered to be HA-MRSA.
      However, 87% of them belonged to staphylococcal cassette chromosome mec (SCCmec)
      types IV and V, which are traditionally associated with CA-MRSA. Surprisingly,
      classical nosocomial SCCmec types I and II represented a minority, whereas SCCmec
      type III was completely absent. By PFGE analysis, four predominant clonal
      lineages and 21 highly variable sporadic genotypes were detected. Twenty-eight
      percent of the MRSA strains studied carried the genes encoding the Panton
      Valentine leukocidin (PVL), of which 21% and 83% were associated with SCCmec
      types IV and V, respectively. Among 289 contact individuals screened for MRSA
      carriage throughout the extended surveillance, a single secondary patient was
      discovered. The possibility of nosocomial transmission could be excluded. The
      high proportions of SCCmec type IV and V strains as well as PVL-positive strains
      suggest strong infiltration of CA-MRSA into our institution. Moreover, the low
      endemic prevalence of MRSA demonstrates that current infection control measures
      are sufficient to limit its spreading and the emergence of large epidemic
      outbreaks.

PMID- 20042626
TI  - The nonserotypeable pneumococcus: phenotypic dynamics in the era of anticapsular
      vaccines.
AB  - Nonserotypeable pneumococci (NSP) are commonly carried by Australian Indigenous
      children in remote communities. The purpose of this study was to characterize
      carriage isolates of NSP from Indigenous children vaccinated with the seven
      valent pneumococcal conjugate vaccine (PCV7) and to use these data to guide
      decisions on reporting of NSP. A total of 182 NSP were characterized by BOX
      typing, antibiogram analysis, and multilocus sequence typing (MLST) of common BOX
      types. NSP positive for the wzg capsule gene were analyzed by a multiplex PCR
      based reverse line blot hybridization assay (mPCR/RLB-H) targeting capsule genes
      to determine the serotype. Among 182 NSP, 49 BOX types were identified. MLST of
      10 representative isolates found 7 STs, including ST448 (which accounted for 11%
      of NSP). Non-penicillin susceptibility was evident in 51% of the isolates.
      Pneumococcal wzg sequences were detected in only 23 (13%) NSP, including 10 that
      contained an approximately 1.2-kb insert in the region. mPCR/RLB-H identified
      serotype 14 wzy sequences in all 10 NSP, and 1 also contained a serotype 3
      specific wze sequence. Among the remaining 13 wzg-positive NSP, few belonged to
      the serotypes represented in PCV7. It appears that most NSP identified in
      Australian Indigenous children are from a true nonencapsulated lineage. Few NSP
      represented serotypes in PCV7 that suppress capsular expression. High rates of
      carriage and penicillin resistance and the occasional presence of capsule genes
      suggest a role for NSP in the maintenance and survival of capsulated pneumococci.
      To avoid the inflation of pneumococcal carriage and antibiotic resistance rates,
      in clinical trials, we recommend separate reporting of rates of capsular strains
      and NSP and the exclusion of data for NSP from primary analyses.

PMID- 20042627
TI  - Further characterization of proteolytic Clostridium botulinum type A5 reveals
      that neurotoxin formation is unaffected by loss of the cntR (botR) promoter sigma
      factor binding site.

PMID- 20042628
TI  - Sequence-based identification of filamentous basidiomycetous fungi from clinical
      specimens: a cautionary note.
AB  - The species-level identification of sterile and/or arthroconidium-forming
      filamentous fungi presumed to be basidiomycetes based upon morphological or
      physiological features alone is usually not possible due to the limited amount of
      hyphal differentiation. Therefore, a reliable molecular approach capable of the
      unambiguous identification of clinical isolates is needed. One hundred sixty
      eight presumptive basidiomycetes were screened by sequence analysis of the
      internal transcribed spacer (ITS) and D1/D2 ribosomal DNA regions in an effort to
      obtain a species identification. Through the use of this approach, identification
      of a basidiomycetous fungus to the species level was obtained for 167/168 of the
      isolates. However, comparison of the BLAST results for each isolate for both
      regions revealed that only 28.6% (48/168) of the isolates had the same species
      identification by use of both the ITS and the D1/D2 regions, regardless of the
      percent identity. At the less stringent genus-only level, the identities for only
      48.8% (82/168) of the isolates agreed for both regions. Investigation of the
      causes for this low level of agreement revealed that 14% of the species lacked an
      ITS region deposit and 16% lacked a D1/D2 region deposit. Few GenBank deposits
      were found to be complete for either region, with only 8% of the isolates having
      a complete ITS region and 10% having a complete D1/D2 region. This study
      demonstrates that while sequence-based identification is a powerful tool for many
      fungi, sequence data derived from filamentous basidiomycetes should be
      interpreted carefully, particularly in the context of missing or incomplete
      GenBank data, and, whenever possible, should be evaluated in light of compatible
      morphological features.

PMID- 20042629
TI  - Results of the Abbott RealTime HIV-1 assay for specimens yielding "target not
      detected" results by the Cobas AmpliPrep/Cobas TaqMan HIV-1 Test.
AB  - No significantly discordant results were observed between the Abbott RealTime HIV
      1 assay and the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (CTM) among 1,190 unique
      clinical plasma specimens obtained from laboratories located in 40 states
      representing all nine U.S. geographic regions and previously yielding "target not
      detected" results by CTM.

PMID- 20042630
TI  - Sodium polyanethole sulfonate as an inhibitor of activation of complement
      function in blood culture systems.
AB  - Sodium polyanethole sulfonate (SPS; trade name, Liquoid) is a constituent in
      culture media used to grow bacteria from blood samples from patients suspected of
      bacteremia. SPS prevents the killing of bacteria by innate cellular and humoral
      factors. We analyzed the effect of SPS on the three complement activation
      pathways: the classical, alternative, and lectin pathways, respectively.
      Inhibition of complement activity by SPS is caused by a blocking of complement
      activation and is not a result of complement consumption. The classical pathway
      is inhibited at SPS concentrations greater than 0.1 mg/ml, and complete
      inhibition is seen at 0.4 mg/ml. An SPS concentration of 0.5 mg/ml completely
      inhibits the binding of C1q and subsequent incorporation of C3, C4, and C9. The
      same was observed for the alternative pathway with an inhibition at SPS
      concentrations from 0.1 mg/ml and a complete inhibition from 0.4 mg/ml. Here,
      properdin binding was completely absent, and no incorporation of C3 and C9 was
      observed. In contrast, the lectin complement pathway remains unaffected at these
      SPS concentrations, and inhibition is first observed from 0.7 mg/ml. A complete
      inhibition required concentrations greater than 1 mg/ml. SPS is used in growth
      media (e.g., BACTEC and BacT/Alert) at concentrations from 0.3 to 0.5 mg/ml. The
      well-known finding that certain bacteria are growth inhibited by blood factors
      could therefore be a consequence of the lectin pathway, which is not inhibited at
      these concentrations. In addition, our findings also open up the possibility of a
      new assay for the assessment of the functional capacity of the lectin complement
      pathway.

PMID- 20042631
TI  - Prevalence and associations of tcpC, a gene encoding a Toll/interleukin-1
      receptor domain-containing protein, among Escherichia coli urinary tract
      infection, skin and soft tissue infection, and commensal isolates.
AB  - TcpC, a new Toll/interleukin-1 receptor domain-containing protein of
      uropathogenic Escherichia coli involved in the suppression of innate immunity,
      was found in 2008. The aim of the present study was to determine the prevalence
      of tcpC and its association with virulence factors and phylogenetic groups among
      strains from a collection of 212 E. coli isolates from urinary tract and skin and
      soft tissue infections and 90 commensal E. coli strains.

PMID- 20042632
TI  - Cytospin-enhanced immunofluorescence and impact of sample quality on detection of
      novel swine origin (H1N1) influenza virus.
AB  - Nasopharyngeal swabs (n = 601) from 278 adult and 323 pediatric patients were
      tested within 24 h of receipt by cytospin-enhanced direct immunofluorescence
      antibody testing (DFA) and real-time reverse transcriptase PCR (RT-PCR) using the
      CDC assay. Cytospin-enhanced DFA detected 230 (84.6%) of 272 swine influenza A
      PCR-positive results overall but 25 (92.6%) of 27 positive results in patients
      less than 5 years old and 208 (96.7%) of 215 positive samples with cycle
      threshold values of <26.

PMID- 20042633
TI  - Computational analysis identifies human adenovirus type 55 as a re-emergent acute
      respiratory disease pathogen.
AB  - Novel human adenoviruses (HAdVs) arise from genome recombination. Analysis of
      HAdV type 55 from an outbreak in China shows a hexon recombination between HAdV
      B11 and HAdV-B14, resulting in a genome that is 97.4% HAdV-B14. Sporadic
      appearances as a re-emergent pathogen and misidentification as "HAdV-B11a" are
      due to this partial hexon.

PMID- 20042634
TI  - Comparison of whole blood, serum, and plasma for early detection of candidemia by
      multiplex-tandem PCR.
AB  - We applied multiplex-tandem PCR (MT-PCR) to 255 EDTA whole-blood specimens, 29
      serum specimens, and 24 plasma specimens from 109 patients with Candida
      bloodstream infection (candidemia) to determine whether a diagnosis could be
      expedited in comparison with the time to diagnosis by the use of standard blood
      culture. Overall, the MT-PCR performed better than blood culture with DNA
      extracted from whole blood from 52/74 (70%) patients, accelerating the time to
      detection (blood culture flagging) and determination of the pathogenic species
      (by use of the API 32C system [bioMerieux, Marcy l'Etoile, France]) by up to 4
      days (mean, 2.2 days; range, 0.5 to 8 days). Candida DNA was detected more often
      in serum (71%) and plasma (75%) than in whole blood (54%), although relatively
      small numbers of serum and plasma specimens were tested. The sensitivity,
      specificity, positive predictive value, and negative predictive value of the
      assay with whole blood were 75%, 97%, 95%, and 85%, respectively. Fungal DNA was
      not detected by MT-PCR in 6/24 (25%) whole-blood samples drawn simultaneously
      with the positive blood culture sample. MT-PCR performed better with whole-blood
      specimens stored at -20 degrees C (75%) and when DNA was extracted within 1 week
      of sampling (66%). The molecular and culture identification results correlated
      for 61 of 66 patients (92%); one discrepant result was due to misidentification
      by culture. All but one sample from 53 patients who were at high risk of
      candidemia but did not have proven disease were negative by MT-PCR. The results
      demonstrate the good potential of MT-PCR to detect candidemia, to provide Candida
      species identification prior to blood culture positivity, and to provide improved
      sensitivity when applied to with serum and plasma specimens.

PMID- 20042635
TI  - ALK5 phosphorylation of the endoglin cytoplasmic domain regulates Smad1/5/8
      signaling and endothelial cell migration.
AB  - Endoglin, an endothelial cell-specific transforming growth factor-beta (TGF-beta)
      superfamily coreceptor, has an essential role in angiogenesis. Endoglin-null mice
      have an embryonic lethal phenotype due to defects in angiogenesis and mutations
      in endoglin result in the vascular disease hereditary hemorrhagic telangiectasia
      type I. Increased endoglin expression in the proliferating endothelium of tumors
      has been correlated with metastasis, tumor grade and decreased survival. Although
      endoglin is thought to regulate TGF-beta superfamily signaling in endothelial
      cells through regulating the balance between two TGF-beta-responsive pathways,
      the activin receptor-like kinase 5 (ALK5)/Smad2/3 pathway and the activin
      receptor-like kinase 1 (ALK1)/Smad1/5/8 pathway, the mechanism by which endoglin
      regulates angiogenesis has not been defined. Here, we investigate the role of the
      cytoplasmic domain of endoglin and its phosphorylation by ALK5 in regulating
      endoglin function in endothelial cells. We demonstrate that the cytoplasmic
      domain of endoglin is basally phosphorylated by ALK5, primarily on serines 646
      and 649, in endothelial cells. Functionally, the loss of phosphorylation at
      serine 646 resulted in a loss of endoglin-mediated inhibition of Smad1/5/8
      signaling in response to TGF-beta and endothelial cell migration, whereas loss of
      phosphorylation at both serines 646 and 649 resulted in a loss of endoglin
      mediated inhibition of Smad1/5/8 signaling in response to bone morphogenetic
      protein-9. Taken together, these results support endoglin phosphorylation by ALK5
      as an important mechanism for regulating TGF-beta superfamily signaling and
      migration in endothelial cells.

PMID- 20042636
TI  - Polymorphisms in fatty-acid-metabolism-related genes are associated with
      colorectal cancer risk.
AB  - Colorectal cancer (CRC) is the third most common malignant tumor and the fourth
      leading cause of cancer death worldwide. The crucial role of fatty acids for a
      number of important biological processes suggests a more in-depth analysis of
      inter-individual differences in fatty acid metabolizing genes as contributing
      factor to colon carcinogenesis. We examined the association between genetic
      variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225
      CRC cases and 2032 controls participating in the European Prospective
      Investigation into Cancer and Nutrition study. Three hundred and ninety two
      single-nucleotide polymorphisms were selected using pairwise tagging with an r(2)
      cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic
      regression models were used to estimate odds ratios and corresponding 95%
      confidence intervals. Haplotype analysis was performed using a generalized linear
      model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15
      (NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential
      vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E
      receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse
      association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG
      and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003,
      respectively) associated with higher risk of CRC. Based on these data, we present
      for the first time the association of HPGD variants with CRC risk. Our results
      support the key role of prostanoid signaling in colon carcinogenesis and suggest
      a relevance of genetic variation in fatty acid metabolism-related genes and CRC
      risk.

PMID- 20042637
TI  - Expression of human papillomavirus type 16 E7 oncoprotein alters keratinocytes
      expression profile in response to tumor necrosis factor-alpha.
AB  - Acute expression of E7 oncogene from human papillomavirus (HPV) 16 or HPV18 is
      sufficient to overcome tumor necrosis factor (TNF)-alpha cytostatic effect on
      primary human keratinocytes. In the present study, we investigated the molecular
      basis of E7-induced TNF resistance through a comparative analysis of the effect
      of this cytokine on the proliferation and global gene expression of normal and E7
      expressing keratinocytes. Using E7 functional mutants, we show that E7-induced
      TNF resistance correlates with its ability to mediate pRb degradation and cell
      transformation. On the other hand, this effect does not depend on E7 sequences
      required to override DNA damage-induced cell cycle arrest or extend keratinocyte
      life span. Furthermore, we identified a group of 66 genes whose expression
      pattern differs between normal and E7-expressing cells upon cytokine treatment.
      These genes are mainly involved in cell cycle regulation suggesting that their
      altered expression may contribute to sustained cell proliferation even in the
      presence of a cytostatic stimulus. Differential expression of TCN1
      (transcobalamin I), IFI44 (Interferon-induced protein 44), HMGB2 (high-mobility
      group box 2) and FUS [Fusion (involved in t(12;16) in malignant liposarcoma)]
      among other genes were further confirmed by western-blot and/or real-time
      polymerase chain reaction. Moreover, FUS upregulation was detected in HPV
      positive cervical high-grade squamous intraepithelial lesions when compared with
      normal cervical tissue. Further evaluation of the role of such genes in TNF
      resistance and HPV-associated disease development is warranted.

PMID- 20042638
TI  - Lysine-specific demethylase 1 (LSD1) is highly expressed in ER-negative breast
      cancers and a biomarker predicting aggressive biology.
AB  - Breast carcinogenesis is a multistep process involving both genetic and
      epigenetic changes. Since epigenetic changes like histone modifications are
      potentially reversible processes, much effort has been directed toward
      understanding this mechanism with the goal of finding novel therapies as well as
      more refined diagnostic and prognostic tools in breast cancer. Lysine-specific
      demethylase 1 (LSD1) plays a key role in the regulation of gene expression by
      removing the methyl groups from methylated lysine 4 of histone H3 and lysine 9 of
      histone H3. LSD1 is essential for mammalian development and involved in many
      biological processes. Considering recent evidence that LSD1 is involved in
      carcinogenesis, we investigated the role of LSD1 in breast cancer. Therefore, we
      developed an enzyme-linked immunosorbent assay to determine LSD1 protein levels
      in tissue specimens of breast cancer and measured very high LSD1 levels in
      estrogen receptor (ER)-negative tumors. Pharmacological LSD1 inhibition resulted
      in growth inhibition of breast cancer cells. Knockdown of LSD1 using small
      interfering RNA approach induced regulation of several proliferation-associated
      genes like p21, ERBB2 and CCNA2. Additionally, we found that LSD1 is recruited to
      the promoters of these genes. In summary, our data indicate that LSD1 may provide
      a predictive marker for aggressive biology and a novel attractive therapeutic
      target for treatment of ER-negative breast cancers.

PMID- 20042639
TI  - The kinase Mirk is a potential therapeutic target in osteosarcoma.
AB  - Osteosarcoma is the most common primary malignant bone tumor affecting children
      and adolescents. The majority of patients are treated by surgery and chemotherapy
      but have limited alternative therapeutic options. Kinases play an important role
      in the growth and survival of tumor cells. We aim to identify specific kinases to
      be vital in the survival of osteosarcoma cells and thus may be a key target in
      creating novel anticancer therapies. A lentiviral short hairpin RNA kinase
      library, screened osteosarcoma cells, identified kinase minibrain-related kinase
      (Mirk) (Dyrk1B) as a potential target. Knockdown Mirk expression could inhibit
      cell growth and induce apoptosis. Chemically synthetic small interfering RNA
      knockdown and complementary DNA rescue assay further confirmed the results from
      the decrease of Mirk gene expression. The relationship between Mirk gene
      expression and the clinical characteristics of patients with osteosarcoma was
      investigated using tissue microarray and immunohistochemistry analysis. The data
      indicate that the overall survival rate of patients with Mirk high staining (high
      levels of Mirk protein expression) is significantly shorter than those with Mirk
      low staining and moderate staining. This highlights Mirk's potential to serve as
      a promising target for molecular therapy in the treatment of osteosarcoma.

PMID- 20042641
TI  - Evaluation of CXCR4 inhibition in the prevention and intervention model of laser
      induced choroidal neovascularization.
AB  - PURPOSE. Endothelial precursor cells (EPCs) derived from hematopoietic stem cells
      (HSCs) have been shown to contribute to choroidal neovascularization by signaling
      through the SDF-1/CXCR4 axis. In a prevention and treatment/intervention modality
      of the laser choroidal neovascularization (CNV) model, the efficacy of CXCR4
      inhibition on reducing choroidal leakage and angiogenesis was evaluated. METHODS.
      CNV in rats was generated by focal rupture of Bruch's membrane with an 810-nm
      diode laser. In the prevention mode, a CXCR4 antagonist (AMD3100) was delivered
      via an osmotic pump 1 day after laser induction. In the intervention mode,
      AMD3100 delivery commenced 14 days after laser induction. Inhibition of CXCR4 was
      determined through leukocyte and SDF-1 actin polymerization blood biomarker
      assays. Leakage was assessed by fluorescein angiography, and CNV lesion size was
      quantified after isolectin B4 endothelial cell staining. SU14813, an anti-VEGFR,
      PDGFR-beta, KIT, and FLT3 inhibitor, was also assessed in an intervention study
      protocol. RESULTS. Inhibition of CXCR4 was demonstrated by an increase in the
      number of blood leukocytes, and diminished SDF-1 induced actin polymerization in
      whole blood. CNV leakage and neovascularization were inhibited when the dose
      regimen was initiated 1 day after laser-induced CNV induction. AMD3100 did not
      show efficacy when administered 14 days after lasering. Treatment with SU14813
      significantly decreased CNV leakage and lesion size in an intervention modality.
      CONCLUSIONS. Inhibition of CXCR4 may be useful in preventing neovascularization
      but does not appear to have an effect on already established angiogenesis. A
      multiple receptor tyrosine kinase (RTK) inhibitor approach shows promise for the
      treatment of wet age-related macular degeneration.

PMID- 20042640
TI  - Hypoxia activates the cyclooxygenase-2-prostaglandin E synthase axis.
AB  - Hypoxia-inducible factors (HIFs), in particular HIF-1alpha, have been implicated
      in tumor biology. However, HIF target genes in the esophageal tumor
      microenvironment remain elusive. Gene expression profiling was performed upon
      hypoxia-exposed non-transformed immortalized human esophageal epithelial cells,
      EPC2-hTERT, and comparing with a gene signature of esophageal squamous cell
      carcinoma (ESCC). In addition to known HIF-1alpha target genes such as carbonic
      anhydrase 9, insulin-like growth factor binding protein-3 (IGFBP3) and
      cyclooxygenase (COX)-2, prostaglandin E synthase (PTGES) was identified as a
      novel target gene among the commonly upregulated genes in ESCC as well as the
      cells exposed to hypoxia. The PTGES induction was augmented upon stabilization of
      HIF-1alpha by hypoxia or cobalt chloride under normoxic conditions and suppressed
      by dominant-negative HIF-1alpha. Whereas PTGES messenger RNA (mRNA) was
      negatively regulated by normoxia, PTGES protein remained stable upon
      reoxygenation. Prostaglandin E(2) (PGE(2)) biosynthesis was documented in
      transformed human esophageal cells by ectopic expression of PTGES as well as RNA
      interference directed against PTGES. Moreover, hypoxia stimulated PGE(2)
      production in a HIF-1alpha-dependent manner. In ESCC, PTGES was overexpressed
      frequently at the mRNA and protein levels. Finally, COX-2 and PTGES were
      colocalized in primary tumors along with HIF-1alpha and IGFBP3. Activation of the
      COX-2-PTGES axis in primary tumors was further corroborated by concomitant
      upregulation of interleukin-1beta and downregulation of hydroxylprostaglandin
      dehydrogenase. Thus, PTGES is a novel HIF-1alpha target gene, involved in
      prostaglandin E biosynthesis in the esophageal tumor hypoxic microenvironment,
      and this has implications in diverse tumors types, especially of squamous origin.

PMID- 20042642
TI  - Blood-retinal barrier glycerol permeability in diabetic macular edema and healthy
      eyes: estimations from macular volume changes after peroral glycerol.
AB  - PURPOSE: To compare the changes in macular volume (MV) between healthy subjects
      and patients with diabetic macular edema (DME) after an osmotic load and to
      determine the glycerol permeability (P(gly)) of the blood-retinal barrier (BRB).
      METHODS: In this unmasked study, 13 patients with DME and 5 healthy control
      subjects ingested a glycerol solution (0.57 g/mL) of 3 mL/kg body weight
      (maximum, 250 mL). Subsequently, the MV determined by the retinal maps provided
      by the optical coherence tomography (OCT) fast macular thickness protocol was
      monitored at 12 time points for 180 minutes. A mathematical model of glycerol and
      osmotic water movements across the BRB was constructed to estimate P(gly).
      RESULTS: Median MV decreased from 7.30 mm(3) (range, 6.68-7.35) to the maximum
      median DeltaMV of -0.30 mm(3) (25%-75% quartile: -0.34 to -0.25) in the healthy
      volunteers and from 7.97 mm(3) (range, 6.85-9.89) to DeltaMV of -0.14 mm(3) (25%
      75% quartile: -0.19 to -0.08) in the diabetic group (intergroup difference: P <
      0.05). P(gly) was 6.1 x 10(-6) (SE 1.8 x 10(-6)) and 74 x 10(-6) (SE 42 x 10(-6))
      cm/s in the healthy and diabetic participants, respectively (P < 0.0001). No
      rebound phenomenon was observed in either group. CONCLUSIONS: The maximum
      reduction in MV was doubled in the healthy group compared with the diabetic
      group, whereas the glycerol permeability was 12 times higher in the diabetic
      participants. These findings confirm the paradigm of BRB breakdown in DME, but
      also suggest a novel procedure for the determination of retinal permeability to
      various agents, which is independent of the vitreous condition
      (ClinicalTrials.gov number, NCT00333671).

PMID- 20042643
TI  - Molecular mechanism of proinflammatory cytokine-mediated squamous metaplasia in
      human corneal epithelial cells.
AB  - PURPOSE: The cornified envelope protein small proline-rich protein 1B (SPRR1B) is
      a biomarker for squamous metaplasia. Proinflammatory cytokines IL-1beta and IFN
      gamma are potent inducers of ocular surface keratinization and SPRR1B expression.
      Here the molecular mechanisms controlling SPRR1B gene expression in response to
      IL-1beta and IFN-gamma are elucidated. METHODS: A 3-kb fragment of the SPRR1B
      gene 5'-flanking region was amplified from human chromosome 1, sequentially
      deleted, and cloned into a luciferase vector. Constructs were transiently
      transfected into human corneal epithelial cells, and activity was assessed in
      response to IL-1beta, IFN-gamma, or basal medium. Functional cis-elements
      responding to IL-1beta and IFN-gamma were characterized by site-directed
      mutagenesis and gel mobility shift assay. Effects of mitogen-activated protein
      kinases p38, ERK, and JNK were assessed using inhibitors and dominant-negative
      mutants. Results were validated by real-time RT-PCR. RESULTS: The first 620 bp of
      the SPRR1B 5'-flanking region regulated constitutive expression and increased
      promoter activity in response to IL-1beta and IFN-gamma. Corresponding cis
      elements for IL-1beta and IFN-gamma were bound by cAMP response element binding
      protein (CREB) and zinc-finger E-box binding homeobox 1 (ZEB1), respectively.
      Inhibition of p38 abolished the stimulatory effects of IL-1beta and IFN-gamma on
      SPRR1B, whereas inhibition of JNK and ERK had no effect. Dominant-negative
      mutants targeting p38alpha and p38beta2 blocked cytokine-induced SPRR1B promoter
      activity and mRNA expression. CONCLUSIONS: SPRR1B is upregulated by the
      proinflammatory cytokines IL-1beta and IFN-gamma via p38 MAPK-mediated signaling
      pathways that lead to the activation of transcription factors CREB and ZEB1,
      respectively. These results identify key intracellular signaling intermediates
      involved in the pathogenesis of immune-mediated ocular surface squamous
      metaplasia.

PMID- 20042644
TI  - Minimal effects of VEGF and anti-VEGF drugs on the permeability or selectivity of
      RPE tight junctions.
AB  - PURPOSE: Bevacizumab and ranibizumab are currently used to treat age-related
      macular degeneration by neutralizing vascular endothelial growth factor (VEGF).
      In this study, the potential side effects on the outer blood-retinal barrier were
      examined. METHODS: Human fetal RPE (hfRPE) cells were used because they are
      highly differentiated in culture. The claudin composition of RPE tight junctions
      was determined by RT-PCR, immunoblot analysis, and immunofluorescence. ELISA
      assays monitored the secretion and trafficking of VEGF and a fluid-phase marker,
      methylpolyethylene glycol (mPEG). Tight junction functions were assessed by the
      conductance of K(+) and Na(+) (derived from the transepithelial electrical
      resistance, TER) and the flux of NaCl and mPEG. RESULTS: Claudin-3, claudin-10,
      and claudin-19 were detected in RPE tight junctions. VEGF was secreted in equal
      amounts across the apical and basolateral membranes, but the apical membrane was
      more active in endocytosing and degrading VEGF. Exogenous VEGF and mPEG crossed
      the RPE monolayer by transcytosis, predominantly in the apical-to-basal
      direction. RPE tight junctions were selective for K(+), but did not discriminate
      between Na(+) and Cl(-). VEGF, bevacizumab, and ranibizumab had minimal effects
      on TER, permeation of mPEG, and selectivity for K(+), Na(+), and Cl(-). They had
      minimal effects on the expression and distribution of the claudins. CONCLUSIONS:
      RPE has mechanisms for maintaining low concentrations of VEGF in the subretinal
      space that include endocytosis and degradation and fluid-phase transcytosis in
      the apical-to-basal direction. RPE tight junctions are selective for K(+) over
      Na(+) and Cl(-). Permeability and selectivity of the junctions are not affected
      by VEGF, bevacizumab, or ranibizumab.

PMID- 20042645
TI  - Muscarinic acetylcholine receptor localization and activation effects on ganglion
      response properties.
AB  - PURPOSE: The activation and blockade of muscarinic acetylcholine receptors
      (mAChRs) affects retinal ganglion cell light responses and firing rates. This
      study was undertaken to identify the full complement of mAChRs expressed in the
      rabbit retina and to assess mAChR distribution and the functional effects of
      mAChR activation and blockade on retinal response properties. METHODS: RT-PCR,
      Western blot analysis, and immunohistochemistry were used to identify the
      complement and distribution of mAChRs in the rabbit retina. Extracellular
      electrophysiology was used to determine the effects of the activation or blockade
      of mAChRs on ganglion cell response properties. RESULTS: RT-PCR of whole neural
      retina resulted in the amplification of mRNA transcripts for the m1 to m5 mAChR
      subtypes. Western blot and immunohistochemical analyses confirmed that all five
      mAChR subtypes were expressed by subpopulations of bipolar, amacrine, and
      ganglion cells in the rabbit retina, including subsets of cells in cholinergic
      and glycinergic circuits. Nonspecific muscarinic activation and blockade resulted
      in the class-specific modulation of maintained ganglion cell firing rates and
      light responses. CONCLUSIONS: The expression of mAChR subtypes on subsets of
      bipolar, amacrine, and ganglion cells provides a substrate for both enhancement
      and suppression of retinal responses via activation by cholinergic agents. Thus,
      the muscarinic cholinergic system in the retina may contribute to the modulation
      of complex stimuli. Understanding the distribution and function of mAChRs in the
      retina has the potential to provide important insights into the visual changes
      that are caused by decreased ACh in the retinas of Alzheimer's patients and the
      potential visual effects of anticholinergic treatments for ocular diseases.

PMID- 20042646
TI  - The effect of the asphericity of myopic laser ablation profiles on the induction
      of wavefront aberrations.
AB  - PURPOSE: To compare the effects of laser profile asphericity on the induction of
      wavefront aberrations, susceptibility to decentration, and depth of focus in a
      polymethylmethacrylate (PMMA) model. METHODS: Four PMMA lenses received an
      excimer laser ablation of -6 D with a 6-mm optical zone and different amounts of
      primary spherical aberration (Z(4)(0)): 0, -0.346, -1.038, and -2.076 microm. The
      curvature of each lens was measured by using surface profilometry, and wavefront
      changes were computed from curvature differences. Changes in optical quality were
      compared by treatment simulation of 13 real myopic eyes. The influence of pupil
      diameter, ablation decentration, and defocus on retinal image quality was
      measured by using the optical transfer function-based visual Strehl ratio
      (VSOTF). RESULTS: Aspheric ablation profiles induced significantly less primary
      but higher secondary spherical aberration (Z(6)(0)) than did the standard
      profile; however, Z(4)(0) compensation was incomplete. Simulated treatments with
      aspheric profiles resulted in significantly better retinal image quality and
      higher decentration tolerance than did the standard profile. Optical depth of
      focus was not affected with a 3-mm pupil, whereas with a 6-mm pupil, there was a
      small but statistically significant decrease in depth of focus. CONCLUSIONS:
      Aspheric laser profiles showed theoretical optical benefits over standard
      ablation profiles for the treatment of myopia, including terms of decentration
      tolerance. However, there remained profound induction and thus, undercorrection
      of Z(4)(0), due to loss of laser ablation efficiency in the lens periphery.

PMID- 20042647
TI  - Genotypic influences on severity of exudative age-related macular degeneration.
AB  - PURPOSE: Major genetic risk factors have recently been identified for age-related
      macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk
      polymorphisms. The study was conducted to establish correlations between the AMD
      genotype and both the phenotype and severity of AMD. METHODS: In a prospective
      cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n
      = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for
      the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the
      at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at
      risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD
      was based on fluorescein angiography. RESULTS: Mean age at presentation was
      significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4
      presented more often with bilateral CNV and fibrovascular scars than did patients
      in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower
      visual acuity (VA) in the first affected eye than did patients in group 1 (P <
      0.02). Patients in group 2 presented with worse VA than did patients in group 3
      (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of
      the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P <
      0.026). CONCLUSIONS: This study demonstrates an association between the at-risk
      allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and
      poor VA. Individuals double homozygous for both at-risk alleles had a higher risk
      of being affected with a severe form of AMD at an earlier age.

PMID- 20042648
TI  - Scotopic electrophysiology of the retina during transient hyperglycemia in type 2
      diabetes.
AB  - PURPOSE: To examine dark-adapted retinal function in subjects with type 2
      diabetes during transient hyperglycemia. METHODS: Twenty-four subjects with type
      2 diabetes and minimal diabetic retinopathy were randomized to an oral glucose
      tolerance test (OGTT) or a fasting regimen. One study eye was kept in the dark
      adapted state at all times. Full-field electroretinography (ffERG) and blood
      glucose measurements were performed at baseline and after 20, 80, 140, and 200
      minutes. RESULTS: Mean capillary glucose had increased 162% from the fasting
      baseline value when the concentration peaked in the OGTT group after 80 minutes
      (P < 0.0001). Concomitantly, rod b-wave amplitude had increased by 34% (P =
      0.0007), whereas the a- and b-wave amplitudes of the standard combined rod-cone
      response had increased by 17% (P = 0.0013 and P = 0.0064). The dark-adapted 30-Hz
      flicker response was unaffected by hyperglycemia. The scotopic ffERG amplitudes
      rose and fell in phase with the glycemia. Implicit times did not change with the
      rise and fall in glycemia. CONCLUSIONS: The change in scotopic signaling
      amplitude in the outer and middle layers of retina in subjects with diabetes was
      proportional to the change in capillary glucose. Cone amplitude was not
      influenced by hyperglycemia in this study.

PMID- 20042649
TI  - Visual experience-independent functional expression of NMDA receptors in the
      developing rabbit retina.
AB  - PURPOSE: Activation of the NMDA glutamate receptors is critical for the
      initiation of synaptic plasticity. In the developing rat retina, NMDA receptor
      function has been associated with visual experience, though the light-dependent
      regulation of the subunit composition of the NMDA receptors is controversial. In
      the present study, the functional expression of NMDA receptors in the developing
      rabbit retina was characterized and the impact of light deprivation on how the
      subunit composition of NMDA receptors is regulated was examined. METHODS:
      Antibodies against NR1 and NR2A/B were used to examine neonatal expression
      patterns of the NMDA receptor subunits. Furthermore, the functional NMDA
      receptors were mapped using the agmatine (AGB) activation assay. RESULTS:
      Although NR1 and NR2A/B subunit immunoreactivity was prominently detectable only
      immediately after birth, AGB activation assay showed that functional NMDA
      receptors could be identified as early as embryonic day 21. No significant
      difference was observed between normal- and dark-reared animals in terms of their
      NR1 and NR2A/B expression. In addition, a comparison of AGB permeation between
      normal- and dark-reared animals showed no difference in functional expression of
      NMDA receptors. CONCLUSIONS: These results indicate that NMDA receptors
      participate in the synaptic maturation of retinal circuits during the early
      stages of development but that the functional NMDA receptors, including their
      subunit composition, in the developing rabbit retina are independent of the
      rabbit's visual experience.

PMID- 20042650
TI  - Presbyopic spectacle coverage, willingness to pay for near correction, and the
      impact of correcting uncorrected presbyopia in adults in Zanzibar, East Africa.
AB  - PURPOSE: To assess presbyopic spectacle coverage, willingness to pay, and the
      impact of correcting uncorrected presbyopia in individuals 40 years of age and
      older in Zanzibar and whether assessment of presbyopia can be incorporated into
      Rapid Assessment of Blindness (RAAB) surveys. METHODS: A cross-sectional,
      population-based survey of presbyopia was incorporated into a RAAB survey. The
      sample size of 400 included individuals older than 50 years (from RAAB survey)
      and those 40 to 50 years old (from the same household) who had a corrected visual
      acuity (VA) of at least 6/18 in either eye. An Ophthalmic Clinical Officer (OCO)
      administered visual function (VF) and quality of life (QOL) questionnaires
      followed by clinical assessment by an optometrist. Participants requiring a
      simple near addition were dispensed free readymade spectacles. The same team
      traced participants 6 months later and readministered the questionnaires. Those
      requiring new spectacles had their near VA measured and were given spectacles.
      RESULTS: Three hundred eighty-one participants were examined. The prevalence of
      presbyopia was 89.2% (340/381) and spectacle coverage was only 17.6%. Barriers to
      accessing services included spectacles not being a priority and lack of money. At
      follow-up, 175 (93.6%) of 187 participants given spectacles still had them. Mean
      satisfaction was high at 89.5%. The mean amount participants were willing to pay
      for spectacles had increased from 2.17 USD at baseline to 3.14 USD at follow-up.
      The impact of correcting presbyopia on VF produced an effect size of 2.90 and
      effect sizes ranging from 1.15 to 3.90 for mean QoL scores. CONCLUSIONS: This
      study highlights the value of correcting presbyopia from the community
      perspective and the necessity of providing affordable, quality, and accessible
      near spectacles at the primary health level.

PMID- 20042651
TI  - The sensitivity of the 2- to 4-month-old human infant accommodation system.
AB  - PURPOSE: The goal of this study was to compare objectively the sensitivity of the
      accommodation system in human infants and adults under binocular and monocular
      viewing conditions. METHODS: Full-term infants from 2 to 4 months of age and pre
      presbyopic adults were presented with a high-contrast cartoon stimulus moving
      sinusoidally in diopters around a mean position of 2 D (50 cm). Three stimulus
      amplitudes were used in one trial (0.25, 0.50, and 0.75 D), with unpredictable
      stimulus motion during each amplitude change. Eccentric photorefraction was used
      to record accommodative responses at 25 Hz. The stimulus was made monocular by
      placing an infrared filter over the right eye, to block visible light but pass
      the near-infrared wavelength of the photorefractor and allow responses to be
      recorded from both eyes. RESULTS: Fourier analysis was used to determine the
      accommodative response at the frequency of the stimulus. Significant signal-to
      noise ratios indicated that, on average, the 2- to 4-month-old infants generated
      an accommodative response to at least the 0.75 D amplitude monocular stimulus and
      the 0.75 and 0.50 D binocular stimuli. Adults responded to the 0.25 D amplitude
      both binocularly and monocularly. CONCLUSIONS: In infants 2 to 4 months of age,
      the developing visual system compensates for small changes in defocus relative to
      the typical amounts of hyperopic refractive error found at that age.

PMID- 20042652
TI  - In search of the identity of the XAP-1 antigen: a protein localized to cone outer
      segments.
AB  - PURPOSE: To determine the identity of the XAP-1 antigen. The XAP-1 antibody has
      been used by many investigators and is recognized as an index of photoreceptor
      outer segment maturity, yet its antigen remains unknown. METHODS: Previous
      studies documented that the XAP-1 antigen is a photoreceptor membrane-associated
      protein. To enrich for this protein, the authors prepared outer segment
      preparations from mouse retinas. Crude membrane and cytoplasmic fractions from
      this preparation were then generated using ultracentrifugation. Proteins were
      solubilized using n-dodecyl beta-D-maltoside and separated using SDS-PAGE.
      Aliquots of the crude membrane fraction were run on multiple lanes of a single
      gel, one lane of which was transferred to PVDF membrane and probed with the XAP-1
      antibody. The remaining lanes were silver-stained. Very careful alignment of the
      Western blot with the silver-stained lanes indicated the presence of a single
      lightly stained band at the same position as the immunopositive band. nanoLC-ESI
      MS/MS analysis was performed on the pooled protein bands. On determining the
      protein identity, confirmatory Western blot analysis and immunohistochemistry
      studies were performed. RESULTS: Western blot analysis performed using the XAP-1
      antibody indicated a single immunoreactive band at approximately 74 kDa in
      lysates from both total outer segment and crude membrane preparations. No
      immunoreactive band was present in the cytoplasmic lysate. MS analysis of pooled
      silver stained bands determined that the XAP-1 antigen is Grp78. Western blot
      analysis and immunohistochemistry both support this identification. CONCLUSIONS:
      Present evidence indicates that the XAP-1 antigen is Grp78, a protein that has
      been previously documented in the interphotoreceptor matrix surrounding cones.

PMID- 20042654
TI  - Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in
      cats.
AB  - PURPOSE: To investigate the effects of acute hyperglycemia on retinal
      microcirculation and endothelial function in cats and removal of superoxide to
      prevent retinal endothelial dysfunction from hyperglycemia. METHODS:
      Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the
      plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to
      measure the vessel diameter (D) and blood velocity (V) simultaneously and
      calculated retinal blood flow (RBF) in second-order retinal arterioles in cats.
      Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium
      independent vasodilator sodium nitroprusside (SNP) were administered into the
      vitreous cavity to evaluate endothelial function in the retinal arterioles. To
      control osmolality, 25% mannitol was administered the same way. Systemic
      hyperoxia was induced to noninvasively examine endothelial function during
      hyperglycemia. To determine the effect of the superoxide on the hyperglycemia
      induced changes in the retinal circulation, 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14
      days before the experiment. RESULTS: The D, V, and RBF increased with acute
      hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V,
      and RBF significantly declined, whereas SNP-induced increases were unattenuated
      during acute hyperglycemia. Return of the decreased RBF to baseline after
      cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute
      hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK
      induced increase in RBF during hyperglycemia. CONCLUSIONS: The results suggest
      that acute hyperglycemia increases RBF via increased osmolality and may cause
      retinal endothelial dysfunction partially via increased oxidative stress.
      Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial
      function during hyperglycemia.

PMID- 20042653
TI  - An ecological correlation study of late age-related macular degeneration and the
      complement factor H Y402H polymorphism.
AB  - PURPOSE: To investigate whether variation in the distribution of the risk allele
      frequency of the Y402H single-nucleotide polymorphism (SNP) across various
      ethnicities and geographic regions reflects differences in the prevalence of late
      age-related macular degeneration (AMD) in those ethnicities. METHODS: Published
      data were obtained via a systematic search. Study samples were grouped into
      clusters by ethnicity and geographic location and the Spearman correlation
      coefficient of the prevalence of late AMD and risk allele frequencies was
      calculated across clusters. RESULTS: Across all ethnicities, AMD prevalence was
      seen to increase with age. Populations of European descent had both higher risk
      allele frequencies and prevalence of late AMD than did Japanese, Chinese, and
      Hispanic descendants. Results for African descendants were anomalous: although
      allele frequency was similar to that in European populations, the age-specific
      prevalence of late AMD was considerably lower. The correlation coefficient for
      the association between allele frequency and AMD prevalence was 0.40 (95%
      confidence interval [CI] = -0.36 to 0.84, P = 0.28) in all populations combined
      and 0.71 (95% CI = 0.02-0.94, P = 0.04) when people of African descent were
      excluded. CONCLUSIONS: Evidence was found at the population level to support a
      positive association between the Y204H risk allele and the prevalence of AMD
      after exclusion of studies undertaken on persons of African ancestry. Data in
      African, Middle Eastern, and South American populations are needed to provide a
      better understanding of the association of late AMD genetic risk across
      ethnicities.

PMID- 20042655
TI  - Regulation of VEGF-A in uveal melanoma.
AB  - PURPOSE: Blood vessels are important constituents of intraocular uveal melanoma
      (UM), but whether angiogenesis is regulated by environmental factors such as
      ischemia or by genetic mechanisms is not known. This study was undertaken to
      examine the regulation of the proangiogenic factor vascular endothelial growth
      factor (VEGF-A). METHODS: Cell lines and primary tumors were tested for
      expression of VEGF-A, under normoxic and hypoxic conditions, using quantitative
      PCR, ELISA, WST-1 viability, and in-cell Western experiments. VEGF-A serum levels
      were determined by ELISA. RESULTS: Hypoxia induced expression of HIF-1alpha and
      VEGF-A in UM cell lines and primary tumor cultures, but it did not influence
      proliferation. VEGF-A expression in primary tumors was variable, demonstrating no
      correlation with specific histologic markers or prognosis. However, VEGF-A levels
      were significantly raised in UM patients with metastases compared with those
      without metastases (P < 0.001). CONCLUSIONS: VEGF-A expression by UM cells is
      mainly controlled by hypoxia and involves the HIF-1alpha pathway, thus indicating
      an important role for the tumor cell environment. Metastases led to increased
      serum VEGF-A levels, indicating that VEGF-A may be involved in the growth of
      metastases.

PMID- 20042656
TI  - Epithelial-mesenchymal transition and proliferation of retinal pigment epithelial
      cells initiated upon loss of cell-cell contact.
AB  - PURPOSE: Molecular mechanisms that initiate epithelial-mesenchymal transition
      (EMT) involved in ocular fibrotic complications remain elusive. Studies were
      conducted to examine the role of cell-cell contact in regulating EMT and
      proliferation of retinal pigment epithelial (RPE) cells. METHODS: Porcine RPE
      cells were isolated as sheets and cultured in vitro on lens capsules. Cell
      morphology was examined by microscopy. Western blot analysis and immunostaining
      were used to follow protein expression. Cell proliferation and RPE function were
      assessed by BrdU incorporation and phagocytosis assay, respectively. RESULTS: RPE
      cells in the center of each sheet maintained cell-cell contacts and retained a
      differentiated phenotype. Disruption of cadherin function in these cells resulted
      in the loss of cell-cell contact and the concomitant induction of mesenchymal
      marker protein expression and cell proliferation. RPE cells at the edge of the
      sheet migrated away from the sheet, underwent EMT, and initiated proliferation,
      which was accompanied by a switch in cadherin expression from P-cadherin to N
      cadherin. Although TGF-beta is thought to be a classic inducer of EMT, it was
      unable to initiate EMT in RPE cells maintaining cell-cell contact. However,
      change to alpha-SMA-positive myofibroblasts was induced by TGF-beta in cells that
      had already undergone EMT. CONCLUSIONS: EMT and the onset of proliferation in RPE
      cells is initiated by loss of cell-cell contact. TGF-beta cannot initiate EMT or
      the proliferation of RPE cells maintaining cell-cell contact but appears to play
      an important secondary role downstream of EMT in inducing transition to a
      myofibroblast phenotype-a phenotype linked to the development of fibrotic
      complications.

PMID- 20042657
TI  - Visual field progression differences between normal-tension and exfoliative high
      tension glaucoma.
AB  - PURPOSE: To compare the pattern, location, and rate of visual field (VF) change
      in normal-tension (NTG) and exfoliative high-tension glaucoma (XHTG). METHODS:
      Records of all patients with glaucoma in the New York Glaucoma Progression Study
      with five or more VF tests were reviewed. Patients were divided into NTG (all
      known IOP < 21 mm Hg) and XHTG (untreated IOP >or= 21 mm Hg) groups. Automated
      pointwise linear regression analysis determined global and localized rates of
      change. RESULTS: There were 139 NTG and 154 XHTG eyes. Patients with XHTG were
      significantly older than those with NTG (mean +/- SD: 72.6 +/- 9.4 years vs. 62.7
      +/- 12.8 years, P < 0.01), had higher mean IOPs (16.5 +/- 3.2 mm Hg vs. 13.3 +/-
      2.0 mm Hg, P < 0.01) and greater central corneal thickness (CCT, 544.0 +/- 35.7
      microm vs. 533.9 +/- 35.9 microm; P = 0.01). During a similar period, XHTG
      progressed globally almost twice as rapidly as did NTG (-0.64 +/- 0.7 dB/y vs. 
      0.35 +/- 0.3 dB/y, P < 0.01), which became nonsignificant after adjustment for
      differences in age, mean IOP, and CCT. In a multivariate model, variables
      significantly associated with progression were higher mean IOP (odds ratio [OR]:
      1.09, P = 0.03) and decreased CCT (OR/40 mum thinner: 1.37, P = 0.03).
      Progression within the paracentral VF was more common in the NTG group (75% vs.
      57.3%, P = 0.04). The most important factor associated with paracentral
      progression among eyes that reached a progression outcome was the diagnosis of
      NTG. CONCLUSIONS: XHTG and NTG eyes progress at a similar global rate after
      adjustment for differences in IOP, CCT, and age. However, NTG eyes progress more
      often in the central VF, independent of other factors. Glaucoma surveillance in
      eyes with open-angle glaucoma and statistically normal IOP should include
      periodic assessment of the central field.

PMID- 20042658
TI  - Intracellular thiol redox status regulates lymphangiogenesis and dictates corneal
      limbal graft survival.
AB  - PURPOSE: Compounds regulating intracellular thiol redox status, such as N,N
      diacetyl-L-cystine dimethylester (NM(2)), were shown to prolong corneal graft
      survival in a penetrating keratoplasty (PKP) model. However, the effect of NM(2)
      on hemangiogenesis and lymphangiogenesis has not been investigated. The effect of
      manipulating ambient thiol redox status on riskier (higher rejection rate)
      transplantation models, such as limbal graft survival and hemangiogenesis and
      lymphangiogenesis in a corneal suture model, were investigated. METHODS: C57BL/10
      mice that received BALB/c corneas were treated by subconjunctival injection of
      NM(2), and limbal graft survival was assessed. Sutured C57BL/6 received daily
      intraperitoneal injections of NM(2), glutathione diethylester (GSH-OEt), or PBS.
      Lymphatic endothelial cell (LEC) and peritoneal mps were treated with NM(2) or
      GSHOEt, and then VEGFR3, neuropilin-2, podoplanin, and LYVE-1 expression were
      analyzed. Supernatants were collected for analysis of TNF-alpha and VEGF-A levels
      by ELISA. RESULTS: Significantly less cellular infiltration was detected in mice
      with corneal limbal transplant-treated NM(2)-treated mice. Hemangiogenesis and
      lymphangiogenesis were suppressed in the NM(2)-treated mice. NM(2) treatment of
      mps led to reduced levels of VEGFR3, neuropilin-2, podoplanin, and LYVE-1
      expression compared with PBS- or GSHOEt- treated mps, lower levels of TNF-alpha,
      and increased secretion of VEGF. Moreover, NM(2)-treated LECs had reduced levels
      of LYVE-1 and Prox-1. CONCLUSIONS: Reduction of ambient redox status reduced
      inflammatory cell infiltrates. Consequently, reduced inflammatory response might
      have contributed to both the observed prolonged corneal limbal graft survival and
      the attenuated hemangiogenesis and lymphangiogenesis in cornea.

PMID- 20042660
TI  - Interrelationship of optical coherence tomography and multifocal visual-evoked
      potentials after optic neuritis.
AB  - PURPOSE: Acute optic neuritis (ON) is often followed by recovery of visual
      function. Although this recovery is mainly attributable to resolution of the
      acute inflammation, the redistribution of ion channels along the demyelinated
      membrane, and subsequent remyelination, part of it may be the result of neural
      plasticity. In the present study, the interrelationship was examined between
      structural (retinal nerve fiber layer [RNFL] thickness) and functional (amplitude
      of multifocal visual evoked potentials [mfVEPs]) measures of the integrity of the
      visual pathway in the postacute stage of ON, to determine whether there was any
      evidence of ongoing neural reorganization. METHODS: Twenty-five subjects with
      acute unilateral ON underwent serial RNFL thickness measurement and mfVEP
      recording. The inter-eye asymmetry of both measures was analyzed. In the period
      between 6 and 12 months, the subjects were considered free of optic disc edema,
      and that period was used to analyze the structure-function relationship. Twenty
      control subjects were also examined. RESULTS: There were significant but opposite
      changes in RNFL thickness and mfVEP amplitude. The average asymmetry of RNFL
      thickness between affected and fellow eyes increased from 17.5 +/- 11.5 to 21.1
      +/- 12.8 microm (P = 0.0003), indicating progressive axonal loss, whereas mfVEP
      amplitude asymmetry decreased from 46.6 +/- 32.4 to 38.3 +/- 31.1 nV (P =
      0.0015), indicating continuous functional recovery. In comparison to the 6-month
      results, the mfVEP amplitude in the ON eye improved by 17.8%, whereas RNFL
      thickness decreased by 20.8%. The result remained unchanged regardless of the
      degree of optic nerve remyelination. CONCLUSIONS: The finding of structural
      functional discrepancy at the postinflammatory stage may support the concept that
      neural plasticity contributes to functional recovery after acute ON.

PMID- 20042661
TI  - Increased sequestration of matrix metalloproteinases in ageing human Bruch's
      membrane: implications for ECM turnover.
AB  - PURPOSE: The ageing of Bruch's membrane is associated with progressive reduction
      in the degradation of the capacity for ECM turnover mediated by the matrix
      metalloproteinase (MMP) system. In this study, the free and bound pools of all
      gelatinase species were quantified to aid in assessing the likelihood of reduced
      availability of pro-MMPs for activation in ageing Bruch's membrane. METHODS:
      Bruch's membrane from macular locations (10 eyes; donor age range, 21-84 years)
      was mounted in Ussing chambers and eluted with phosphate-buffered saline to
      release the free pool of MMPs. Free and bound pools of MMPs were subjected to
      gelatin zymography, and individual gelatinase species were quantified by
      densitometric scans. RESULTS: The zymograms displayed six gelatinase species:
      four corresponding to the pro- and active forms of MMP-2 and -9 and two high
      molecular-weight polymeric forms designated HMW1 and -2, corresponding to
      approximate molecular masses of 195 and 391 kDa, respectively. The ageing of
      Bruch's membrane was associated with an exponential increase in the percentage of
      pro-MMPs bound to the membrane (pro-MMP-2: %age bound = 0.54 exp(0.04 x age), r =
      0.87, P < 0.01; and pro-MMP-9: %age bound = 5.0 exp(0.03 x age), r = 0.8, P <
      0.01). A similar exponential increase was seen in the percentage of bound HMW1
      species (%bound = 11.7 exp(0.018 x age; P < 0.05). The HMW2 species was virtually
      all bound to the membrane, but some release was observed in the very elderly.
      CONCLUSIONS: The ageing of Bruch's membrane was associated with progressive
      sequestration of MMPs reducing the free concentration and potential for
      activation. These changes may underlie the reduction in degradation that leads to
      the age-related increase in the thickness of the membrane.

PMID- 20042659
TI  - Systemic propranolol reduces b-wave amplitude in the ERG and increases IGF-1
      receptor phosphorylation in rat retina.
AB  - PURPOSE: To determine whether systemic application of propranolol, a nonselective
      beta-adrenergic receptor antagonist, with an osmotic pump will decrease the b
      wave amplitude of the electroretinogram (ERG) and increase insulin-like growth
      factor (IGF)-1 receptor signaling. METHODS: Young rats at 8 weeks of age were
      treated with saline, phentolamine, a nonselective alpha-adrenergic receptor
      antagonist, or propranolol, a nonselective beta-adrenergic receptor antagonist,
      delivered by osmotic pumps for 21 days. On the 21st day, all rats underwent
      electroretinographic analyses followed by collection of the retinas for protein
      assessment using Western blot analysis for IGF binding protein 3 (IGFBP3), IGF-1
      receptor (IGF-1R), Akt, extracellular signal-related kinases 1 and 2 (ERK1/2),
      and vascular endothelial cell growth factor (VEGF). RESULTS: Data indicate that
      21 days of propranolol significantly decreased the b-wave amplitude of the ERG.
      The decrease in the b-wave amplitude occurred concurrently with a decrease in
      IGFBP3 levels and an increase in tyrosine phosphorylation of IGF-1 receptor on
      1135/1136. This phosphorylation of IGF-1 receptor led to increased
      phosphorylation of Akt and ERK1/2. VEGF protein levels were also increased.
      CONCLUSIONS: Overall, beta-adrenergic receptor antagonism produced a
      dysfunctional ERG, which occurred with an increase in IGF-1R phosphorylation and
      activation of VEGF. Systemic application of beta-adrenergic receptor antagonists
      may have detrimental effects on the retina.

PMID- 20042662
TI  - Biomechanical properties of keratoconus suspect eyes.
AB  - PURPOSE: Measuring corneal biomechanical properties may help detect keratoconus
      suspect corneas and eliminate the risk of ectasia after LASIK. METHODS: Data of
      504 eyes separated into three groups were retrospectively reviewed: normal (n =
      252), keratoconus suspect (n = 80), and keratoconus (n = 172). Corneal hysteresis
      (CH) and corneal resistance factor (CRF) were measured with an ocular
      biomechanics analyzer. RESULTS: Mean corneal hysteresis was 10.6 +/- 1.4 (SD) mm
      Hg in the normal group, compared with 10.0 +/- 1.6 mm Hg in the keratoconus
      suspect group and 8.1 +/- 1.4 mm Hg in the keratoconus group. The mean CRF was
      10.6 +/- 1.6 mm Hg in the normal group compared with 9.7 +/- 1.7 in the
      keratoconus suspect group and 7.1 +/- 1.6 mm Hg in the keratoconus group. Mean CH
      and CRF were significantly different between the three groups (P < 0.001).
      CONCLUSIONS: CH and CRF alone cannot be used to identify keratoconus suspect
      corneas. Analyzing signal curves obtained with the biomechanics analyzer may
      provide additional valuable information for selecting qualified patients for
      refractive surgery.

PMID- 20042663
TI  - Autosomal recessive retinitis pigmentosa with early macular affectation caused by
      premature truncation in PROM1.
AB  - PURPOSE: To identify the genetic basis of a large consanguineous Spanish pedigree
      affected with autosomal recessive retinitis pigmentosa (arRP) with premature
      macular atrophy and myopia. METHODS: After a high-throughput cosegregation gene
      chip was used to exclude all known RP and Leber congenital amaurosis (LCA)
      candidates, genome-wide screening and linkage analysis were performed. Direct
      mutational screening identified the pathogenic mutation, and primers were
      designed to obtain the RT-PCR products for isoform characterization. RESULTS:
      Mutational analysis detected a novel homozygous PROM1 mutation, c.869delG in exon
      8 cosegregating with the disease. This variant causes a frameshift that
      introduces a premature stop codon, producing truncation of approximately two
      thirds of the protein. Analysis of PROM1 expression in the lymphocytes of
      patients, carriers, and control subjects revealed an aberrant transcript that is
      degraded by the nonsense-mediated decay pathway, suggesting that the disease is
      caused by the absence of the PROM1 protein. Three (s2, s11 and s12) of the seven
      alternatively spliced isoforms reported in humans, accounted for 98% of the
      transcripts in the retina. Given that these three contained exon 8, no PROM1
      isoform is expected in the affected retinas. CONCLUSIONS: A remarkable clinical
      finding in the affected family is early macular atrophy with concentric spared
      areas. The authors propose that the hallmark of PROM1 truncating mutations is
      early and severe progressive degeneration of both rods and cones and highlight
      this gene as a candidate of choice to prioritize in the molecular genetic study
      of patients with noncanonical clinical peripheral and macular affectation.

PMID- 20042664
TI  - The safety of intraocular linezolid in rabbits.
AB  - PURPOSE: Intraocular injection of linezolid, a synthetic oxazolidinone
      antibiotic, was performed in rabbits to assess its safety as a possible treatment
      for endophthalmitis. METHODS: Linezolid, 300 microg/0.1 mL, 200 microg/0.1 mL, or
      100 microg/0.1 mL, was injected into the vitreous of the right eye of 12 rabbits.
      Balanced saline solution was injection into the left eye of each rabbit as a
      control. A standard electroretinogram (ERG) was obtained before injection and
      repeated 2 days and 1 and 4 weeks after injection. Intraocular pressure (IOP) was
      also measured after injection. After the experiment, the rabbits were
      euthanatized and the retinas were examined by light and electron microscopy.
      Differences between the two eyes in the ERGs, IOP, and histopathology were
      recorded. RESULTS: There were no statistically significant differences in the
      electroretinograms obtained between the linezolid-injected eyes and the control
      eyes. Histopathology showed no changes in the study eyes compared with the
      control eyes. CONCLUSIONS: Preservative-free linezolid is nontoxic to the retinas
      of rabbits when injected intravitreally, and this route can therefore be
      considered for the administration of linezolid in the treatment of
      endophthalmitis.

PMID- 20042665
TI  - eNOS knockout mice with advanced diabetic nephropathy have less benefit from
      renin-angiotensin blockade than from aldosterone receptor antagonists.
AB  - While blockade of the renin angiotensin system (RAS) is beneficial in treating
      many patients with diabetic nephropathy, some patients show a poor response. We
      hypothesized that the poor response of RAS blockade is attributed to inability to
      stimulate endothelial nitric oxide. Recently, we reported that diabetic eNOS
      knockout (KO) mice develop advanced diabetic nephropathy similar to human
      disease. Here, we tested the hypothesis that blockade of the RAS would be less
      beneficial in this model than in diabetic wild-type mice. Both enalapril and
      telmisartan were less effective at reducing renal injury in diabetic eNOSKO mice
      compared with diabetic wild-type mice. Blood pressure was only transiently
      reduced by these treatments in diabetic eNOSKO mice and later returned to levels
      similar to that of untreated diabetic eNOSKO mice. Serum aldosterone tended to be
      paradoxically higher with enalapril or telmisartan in diabetic eNOSKO mice,
      whereas these treatments tended to lower aldosterone in diabetic wild-type mice.
      The pathogenic role of aldosterone was demonstrated by the evidence that
      spironolactone significantly reduced blood pressure and prevented renal injury.
      In addition, a higher dose of enalapril also failed to prevent hypertension and
      renal injury in diabetic eNOSKO mice. In conclusion, an impaired endothelial NO
      response could lessen the benefit of RAS inhibition in diabetic renal disease.
      Aldosterone blockade may provide superior protection in this setting.

PMID- 20042666
TI  - A mouse model of lethal synergism between influenza virus and Haemophilus
      influenzae.
AB  - Secondary bacterial infections that follow infection with influenza virus result
      in considerable morbidity and mortality in young children, the elderly, and
      immunocompromised individuals and may also significantly increase mortality in
      normal healthy adults during influenza pandemics. We herein describe a mouse
      model for investigating the interaction between influenza virus and the bacterium
      Haemophilus influenzae. Sequential infection with sublethal doses of influenza
      and H. influenzae resulted in synergy between the two pathogens and caused
      mortality in immunocompetent adult wild-type mice. Lethality was dependent on the
      interval between administration of the bacteria and virus, and bacterial growth
      was prolonged in the lungs of dual-infected mice, although influenza virus titers
      were unaffected. Dual infection induced severe damage to the airway epithelium
      and confluent pneumonia, similar to that observed in victims of the 1918 global
      influenza pandemic. Increased bronchial epithelial cell death was observed as
      early as 1 day after bacterial inoculation in the dual-infected mice. Studies
      using knockout mice indicated that lethality occurs via a mechanism that is not
      dependent on Fas, CCR2, CXCR3, interleukin-6, tumor necrosis factor, or Toll-like
      receptor-4 and does not require T or B cells. This model suggests that infection
      with virulent strains of influenza may predispose even immunocompetent
      individuals to severe illness on secondary infection with H. influenzae by a
      mechanism that involves innate immunity, but does not require tumor necrosis
      factor, interleukin-6, or signaling via Toll-like receptor-4.

PMID- 20042667
TI  - The immunoconjugate "icon" targets aberrantly expressed endothelial tissue factor
      causing regression of endometriosis.
AB  - Endometriosis is a major cause of chronic pain, infertility, medical and surgical
      interventions, and health care expenditures. Tissue factor (TF), the primary
      initiator of coagulation and a modulator of angiogenesis, is not normally
      expressed by the endothelium; however, prior studies have demonstrated that both
      blood vessels in solid tumors and choroidal tissue in macular degeneration
      express endothelial TF. The present study describes the anomalous expression of
      TF by endothelial cells in endometriotic lesions. The immunoconjugate molecule
      (Icon), which binds with high affinity and specificity to this aberrant
      endothelial TF, has been shown to induce a cytolytic immune response that
      eradicates tumor and choroidal blood vessels. Using an athymic mouse model of
      endometriosis, we now report that Icon largely destroys endometriotic implants by
      vascular disruption without apparent toxicity, reduced fertility, or subsequent
      teratogenic effects. Unlike antiangiogenic treatments that can only target
      developing angiogenesis, Icon eliminates pre-existing pathological vessels. Thus,
      Icon could serve as a novel, nontoxic, fertility-preserving, and effective
      treatment for endometriosis.

PMID- 20042668
TI  - Quantitative analysis of three-dimensional human mammary epithelial tissue
      architecture reveals a role for tenascin-C in regulating c-met function.
AB  - Remodeling of the stromal extracellular matrix and elevated expression of
      specific proto-oncogenes within the adjacent epithelium represent cardinal
      features of breast cancer, yet how these events become integrated is not fully
      understood. To address this question, we focused on tenascin-C (TN-C), a stromal
      extracellular matrix glycoprotein whose expression increases with disease
      severity. Initially, nonmalignant human mammary epithelial cells (MCF-10A) were
      cultured within a reconstituted basement membrane (BM) where they formed three
      dimensional (3-D) polarized, growth-attenuated, multicellular acini, enveloped by
      a continuous endogenous BM. In the presence of TN-C, however, acini failed to
      generate a normal BM, and net epithelial cell proliferation increased. To
      quantify how TN-C alters 3-D tissue architecture and function, we developed a
      computational image analysis algorithm, which showed that although TN-C disrupted
      acinar surface structure, it had no effect on their volume. Thus, TN-C promoted
      epithelial cell proliferation leading to luminal filling, a process that we
      hypothesized involved c-met, a proto-oncogene amplified in breast tumors that
      promotes intraluminal filling. Indeed, TN-C increased epithelial c-met expression
      and promoted luminal filling, whereas blockade of c-met function reversed this
      phenotype, resulting in normal BM deposition, proper lumen formation, and
      decreased cell proliferation. Collectively, these studies, combining a novel
      quantitative image analysis tool with 3-D organotypic cultures, demonstrate that
      stromal changes associated with breast cancer can control proto-oncogene
      function.

PMID- 20042669
TI  - Inhibition of PI3K by PX-866 prevents transforming growth factor-alpha-induced
      pulmonary fibrosis.
AB  - Transforming growth factor-alpha (TGFalpha) is a ligand for the epidermal growth
      factor receptor (EGFR). EGFR activation is associated with fibroproliferative
      processes in human lung disease and animal models of pulmonary fibrosis. EGFR
      signaling activates several intracellular signaling pathways including
      phosphatidylinositol 3'-kinase (PI3K). We previously showed that induction of
      lung-specific TGFalpha expression in transgenic mice caused progressive pulmonary
      fibrosis over a 4-week period. The increase in levels of phosphorylated Akt,
      detected after 1 day of doxycycline-induced TGFalpha expression, was blocked by
      treatment with the PI3K inhibitor, PX-866. Daily administration of PX-866 during
      TGFalpha induction prevented increases in lung collagen and airway resistance as
      well as decreases in lung compliance. Treatment of mice with oral PX-866 4 weeks
      after the induction of TGFalpha prevented additional weight loss and further
      increases in total collagen, and attenuated changes in pulmonary mechanics. These
      data show that PI3K is activated in TGFalpha/EGFR-mediated pulmonary fibrosis and
      support further studies to determine the role of PI3K activation in human lung
      fibrotic disease, which could be amenable to targeted therapy.

PMID- 20042670
TI  - Evidence for proteotoxicity in beta cells in type 2 diabetes: toxic islet amyloid
      polypeptide oligomers form intracellularly in the secretory pathway.
AB  - The islet in type 2 diabetes mellitus (T2DM) is characterized by a deficit in
      beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP), a
      protein co-expressed with insulin by beta cells. It is increasingly appreciated
      that the toxic form of amyloidogenic proteins is not amyloid but smaller membrane
      permeant oligomers. Using an antibody specific for toxic oligomers and cryo
      immunogold labeling in human IAPP transgenic mice, human insulinoma and pancreas
      from humans with and without T2DM, we sought to establish the abundance and sites
      of formation of IAPP toxic oligomers. We conclude that IAPP toxic oligomers are
      formed intracellularly within the secretory pathway in T2DM. Most striking, IAPP
      toxic oligomers appear to disrupt membranes of the secretory pathway, and then
      when adjacent to mitochondria, disrupt mitochondrial membranes. Toxic oligomer
      induced secretory pathway and mitochondrial membrane disruption is a novel
      mechanism to account for cellular dysfunction and apoptosis in T2DM.

PMID- 20042671
TI  - Lung chitinolytic activity and chitotriosidase are elevated in chronic
      obstructive pulmonary disease and contribute to lung inflammation.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway
      inflammation and emphysematous alveolar destruction. In this study, we have
      investigated whether chitotriosidase (ChTRase) and acidic mammalian chitinase,
      two chitinases with chitinolytic activity, are selectively augmented in COPD and
      contribute to its pathogenesis. We found that smokers with COPD, but not
      asthmatics, had higher chitinolytic activity and increased levels of ChTRase in
      bronchoalveolar lavage, more ChTRase-positive cells in bronchial biopsies, and an
      elevated proportion of alveolar macrophages expressing ChTRase than smokers
      without COPD or never-smokers. ChTRase accounted for approximately 80% of
      bronchoalveolar lavage chitinolytic activity, while acidic mammalian chitinase
      was undetectable. Bronchoalveolar lavage chitinolytic activity and ChTRase were
      associated with airflow obstruction and emphysema and with the levels of
      interleukin (IL)-1beta, IL-8, tumor-necrosis factor (TNF)-alpha, and its type II
      soluble receptor. Tumor necrosis factor-alpha stimulated ChTRase release only
      from alveolar macrophages from smokers with COPD, and exposure of these cells to
      ChTRase promoted the release of IL-8, monocyte-chemoattractant protein-1, and
      metalloproteinase-9. Finally, ChTRase overexpression in the lung of normal mice
      promoted macrophage recruitment and the synthesis of the murine homologue of IL
      8, keratinocyte-derived cytokine, and of monocyte-chemoattractant protein-1. We
      conclude that pulmonary ChTRase overexpression may represent a novel important
      mechanism involved in COPD onset and progression.

PMID- 20042672
TI  - Plasmacytoid dendritic cells control lung inflammation and monocyte recruitment
      in indirect acute lung injury in mice.
AB  - Indirect acute lung injury (ALI, not caused by a direct insult to the lung)
      represents the first organ dysfunction in trauma patients, with nonpulmonary
      sepsis being the most common cause of indirect ALI. Dendritic cells (DCs) are
      thought to participate in a number of inflammatory lung diseases; however, their
      role in indirect ALI is currently not established. Using a clinically relevant
      model of indirect ALI induced in mice by hemorrhagic shock followed 24 hours
      later by polymicrobial septic challenge, we report that mature DC numbers were
      markedly increased in the lung during indirect ALI. DC depletion induced a
      significant increase in indirect ALI severity, which was associated with enhanced
      lung and plasma proinflammatory cytokine concentration and recruitment of
      proinflammatory CD115(+) monocytes in response to increased lung monocyte
      chemotactic protein-1 production. Among the different DC subpopulations,
      plasmacytoid DCs, which were induced and activated in the lung during indirect
      ALI, were responsible for this effect because their specific depletion reproduced
      the observations made in DC-depleted mice. As the recruitment of monocytes to the
      lung plays a central deleterious role in the pathophysiology of indirect ALI, our
      data therefore position plasmacytoid DCs as important regulators of acute lung
      inflammation.

PMID- 20042673
TI  - Involvement of Wnt signaling in dermal fibroblasts.
AB  - Pachydermoperiostosis (PDP) is a rare disease characterized by unique phenotypes
      of the skin and bone, such as thick skin, implying that it may be caused by
      dysregulation of mesenchymal cells. The aim of this study is to examine the roles
      of dermal fibroblasts in the pathogenesis of pachydermia in association with Wnt
      signaling. The numbers of cultured fibroblasts were compared between healthy
      donors and PDP patients, and mRNA expression profiles in cultured dermal
      fibroblasts were examined by DNA microarray analysis and real-time reverse
      transcription-PCR. DKK1 and beta-catenin protein expressions were also evaluated
      by immunohistochemistry in the skin. To evaluate the in vivo roles of DKK1 in
      mice, DKK1 small interfering RNA was injected to the ears. We found that PDP
      fibroblasts proliferated more than control fibroblasts and that mRNA expression
      of a Wnt signaling antagonist, DKK1, was much lower in PDP fibroblasts than in
      normal ones. Consistently, decreased expression of DKK1 in fibroblasts and
      enhanced expression of beta-catenin were noted in PDP patients. Moreover,
      recombinant human DKK1 protein decreased the proliferation of dermal fibroblasts.
      In accord with the above human studies, intradermal injections of DKK1 small
      interfering RNA into mouse ears increased ear thickness as seen in PDP. Our
      findings suggest that enhanced Wnt signaling contributes to the development of
      pachydermia by enhancing dermal fibroblast functions.

PMID- 20042674
TI  - Chronic morphine administration delays wound healing by inhibiting immune cell
      recruitment to the wound site.
AB  - Patients prescribed morphine for the management of chronic pain, and chronic
      heroin abusers, often present with complications such as increased susceptibility
      to opportunistic infections and inadequate healing of wounds. We investigated the
      effect of morphine on wound-healing events in the presence of an infection in an
      in vivo murine model that mimics the clinical manifestations seen in opioid user
      and abuser populations. We show for the first time that in the presence of an
      inflammatory inducer, lipopolysaccharide, chronic morphine treatment results in a
      marked decrease in wound closure, compromised wound integrity, and increased
      bacterial sepsis. Morphine treatment resulted in a significant delay and
      reduction in both neutrophil and macrophage recruitment to the wound site. The
      delay and reduction in neutrophil reduction was attributed to altered early
      expression of keratinocyte derived cytokine and was independent of macrophage
      inflammatory protein 2 expression, whereas suppression of macrophage infiltration
      was attributed to suppressed levels of the potent macrophage chemoattractant
      monocyte chemotactic protein-1. When the effects of chronic morphine on later
      wound healing events were investigated, a significant suppression in angiogenesis
      and myofibroblast recruitment were observed in animals that received chronic
      morphine administration. Taken together, our findings indicate that morphine
      treatment results in a delay in the recruitment of cellular events following
      wounding, resulting in a lack of bacterial clearance and delayed wound closure.

PMID- 20042675
TI  - Expression of the embryonic stem cell transcription factor SOX2 in human skin:
      relevance to melanocyte and merkel cell biology.
AB  - SOX2 is a gene located on chromosome 3q26.33 that encodes a transcription factor
      important to maintenance of embryonic neural crest stem cell pluripotency. We
      have identified rare SOX2-immunoreactive cells in normal human skin at or near
      the established stem cell niches. Three subsets of SOX2-positive cells were
      defined in these regions: those expressing only SOX2 and those that co-expressed
      SOX2 and either CK20 or microphthalmia-associated transcription factor, which are
      consistent with dichotomous differentiation of SOX2-expressing precursors along
      neuroendocrine (Merkel cell) or melanocytic lines, respectively. Examination of
      Merkel cell carcinomas confirmed nuclear SOX2 expression in this tumor type. In
      human patient melanoma, strong nuclear expression of SOX2 was noted in a subset
      of tumors, and the ability to detect SOX2 in lesional cells significantly
      correlated with primary tumor thickness in a survey cohort. To assess the
      potential role of SOX2 in melanoma growth, an in vivo tumorigenesis assay was
      used. Whereas SOX2 knockdown failed to influence proliferation of cultured
      melanoma cells in vitro, tumor xenografts generated with the SOX2-knockdown cell
      line showed significant decrease in mean tumor volume as compared with controls.
      In aggregate, these findings suggest that SOX2 is a novel biomarker for
      subpopulations of normal skin cells that reside in established stem cell niches
      and that might relate to Merkel cell and melanocyte ontogeny and tumorigenesis.

PMID- 20042676
TI  - Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation
      in clear cell renal cell carcinoma.
AB  - Gremlin1 (GREM1), a bone morphogenetic protein antagonist and putative
      angiogenesis-modulating gene, is silenced by promoter hypermethylation in human
      malignancies. Here we study GREM1 methylation in clear cell renal cell carcinoma
      (ccRCC) and its impact on tumor characteristics and clinical outcome. Three GREM1
      promoter CpG island regions (i, ii, iii) were analyzed by methylation-specific
      PCR and/or bisulfite sequencing in ccRCC cell lines and ccRCCs from two
      independent patient series. Results were correlated with clinicopathological and
      angiogenic parameters. Bisulfite sequencing of ccRCC cell lines showed GREM1
      methylation, associated with absence of GREM1 mRNA. GREM1 methylation prevalence
      in ccRCCs varied between regions: 55%, 24%, and 20% for regions i, ii, and iii,
      respectively. GREM1 region iii methylation was associated with increased tumor
      size (P = 0.02), stage (P = 0.013), grade (P = 0.04), tumor (P = 0.001), and
      endothelial cell (P = 0.0001) proliferation and decreased mean vessel density (P
      = 0.001) in a hospital-based ccRCC series (n = 150). In univariate analysis,
      GREM1 region iii methylated ccRCCs had a significant worse survival when compared
      with unmethylated ccRCCs (hazard ratio [HR] = 2.35, 95% confidence interval
      [CI]:1.29 to 4.28), but not in multivariate analysis (HR = 0.88, 95% CI: 0.45 to
      1.74). In a population-based validation series (n = 185), GREM1 region iii
      methylation was associated with increased Fuhrman grade (P = 0.03) and decreased
      overall survival (P = 0.001) in univariate and multivariate analysis (HR = 2.32,
      95% CI: 1.52 to 3.53 and HR = 2.27, 95% CI: 1.44 to 3.59, respectively). The
      strong correlation between GREM1 region iii promoter methylation and increased
      malignancy and its correlation with active angiogenesis indicates a role for
      GREM1 in ccRCC carcinogenesis and tumor angiogenesis.

PMID- 20042678
TI  - High-resolution ultrasound imaging: a novel technique for the noninvasive in vivo
      analysis of endometriotic lesion and cyst formation in small animal models.
AB  - Endometriosis, the presence of endometrial tissue at ectopic sites, is a highly
      prevalent gynecological disease severely affecting a patient's quality of life.
      To analyze the mechanisms involved in the disease and to identify new molecular
      targets for effective therapies, small animal models are an important approach.
      Herein, we report the first use of high-resolution ultrasound imaging for the in
      vivo analysis of intraperitoneal endometriotic lesions in mice. This noninvasive
      technology allows for the repetitive quantitative analysis of growth, cyst
      development, and adhesion formation of endometriotic lesions with a low intra-
      and interobserver variability. Moreover, it enables one to easily differentiate
      between endometrial cysts and stroma. Accordingly, volume measurements of both
      endometrial cysts and stroma indicated that the initial establishment of
      endometriotic lesions is associated with enhanced cellular proliferation,
      followed by a phase of increased secretory activity of endometrial glands.
      Results of ultrasound analysis correlated well with measurements of lesion
      volumes by caliper and histology. Importantly, ultrasound imaging could be
      performed repetitively and noninvasively and reflected best the in vivo
      situation. The technique could further be demonstrated to successfully monitor
      the significant inhibition of growth of endometriotic lesions after specific
      estrogen receptor destabilizator treatment. Thus, high-resolution ultrasound
      imaging represents an important tool for future preclinical small animal studies,
      which address the pathophysiology of endometriosis and the development of new
      treatment strategies.

PMID- 20042677
TI  - A novel mouse model of inflammatory bowel disease links mammalian target of
      rapamycin-dependent hyperproliferation of colonic epithelium to inflammation
      associated tumorigenesis.
AB  - Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal
      cancer. However, our mechanistic understanding of the link between inflammation
      and tumorigenesis in the colon is limited. Here we established a novel mouse
      model of colitis-associated cancer by genetically inactivating signal transducer
      and activator of transcription 3 (Stat3) in macrophages, with partial deletion in
      other myeloid and lymphoid cells. Inflammation developed in the colon of mutant
      mice spontaneously, and tumor lesions, including invasive carcinoma, arose in the
      inflamed region of the intestine with a frequency similar to that observed in
      human IBD patients. The development of both inflammation and tumors in the mutant
      mice required the presence of microflora. Indeed, inflammation was associated
      with disruption of colonic homeostasis, fulminant epithelial/tumor cell
      proliferation, and activation of the mammalian target of rapamycin (mTOR)-Stat3
      pathway in epithelial and tumor cells. The activation of this pathway was
      essential for both the excess proliferation of epithelial/tumor cells and the
      disruption of colonic homeostasis in the mutant mice. Notably, a similar abnormal
      up-regulation of mTOR-Stat3 signaling was consistently observed in the colonic
      epithelial cells of human IBD patients with active disease. These studies
      demonstrate a novel mouse model of IBD-colorectal cancer progression in which
      disrupted immune regulation, mTOR-Stat3 signaling, and epithelial
      hyperproliferation are integrated and simultaneously linked to the development of
      malignancy.

PMID- 20042679
TI  - Platelet-derived growth factor-B normalizes micromorphology and vessel function
      in vascular endothelial growth factor-A-induced squamous cell carcinomas.
AB  - Vascular endothelial growth factor (VEGF), which is a key regulator of
      angiogenesis, often induces formation of immature vessels with increased
      permeability and reduced vessel functionality. Here, we demonstrate that de novo
      expression of murine (m)VEGF-164 induces malignant and invasive tumor growth of
      HaCaT keratinocytes. However, the mVEGF-164-induced tumors are ulcerated with a
      disorganized epithelium that is interrupted by lacunae with limited basement
      membrane and endothelial cell coverage. Vessel maturation is strongly impaired.
      Tumor and vessel micromorphology are markedly improved by the combined expression
      of human platelet-derived growth factor (hPDGF)-B and mVEGF-164. Although tumor
      size and malignancy are comparable with either mVEGF-164 alone or combined human
      PDGF-B and mVEGF-164 expression, combined hPDGF-B and mVEGF-164 expression leads
      to a more solid and compact tumor tissue with a mature functional tumor
      vasculature and a higher microvessel density, as demonstrated histologically and
      by dynamic contrast-enhanced magnetic resonance imaging. Treatment of the hPDGF-B
      and mVEGF-164-expressing tumors with imatinib mesylate to block PDGF-B signaling
      reverses this effect. In addition, tumor cell invasion of mVEGF-164 transfectants
      and mVEGF-164 plus hPDGF-B transfectants in vivo is associated with a marked
      induction of tumor-derived matrix metalloproteinase-1 and stromal matrix
      metalloproteinase-9 and -13, as was confirmed in three-dimensional organotypic co
      cultures with fibroblasts in vitro. These data clearly demonstrate the need for a
      concerted action of different growth factors in the establishment of solid tumors
      with functional vasculature and emphasize the need for a multifactorial therapy.

PMID- 20042681
TI  - Ectopic T-cell specificity and absence of perforin and granzyme B alleviate
      neural damage in oligodendrocyte mutant mice.
AB  - In transgenic mice overexpressing the major myelin protein of the central nervous
      system, proteolipid protein, CD8+ T-lymphocytes mediate the primarily genetically
      caused myelin and axon damage. In the present study, we investigated the cellular
      and molecular mechanisms underlying this immune-related neural injury. At first,
      we investigated whether T-cell receptors (TCRs) are involved in these processes.
      For this purpose, we transferred bone marrow from mutants carrying TCRs with an
      ectopic specificity to ovalbumin into myelin mutant mice that also lacked normal
      intrinsic T-cells. T-lymphocytes with ovalbumin-specific TCRs entered the mutant
      central nervous system to a similar extent as T-lymphocytes from wild-type mice.
      However, as revealed by histology, electron microscopy and axon- and myelin
      related immunocytochemistry, these T-cells did not cause neural damage in the
      myelin mutants, reflecting the need for specific antigen recognition by cytotoxic
      CD8+ T-cells. By chimerization with bone marrow from perforin- or granzyme B
      (Gzmb)-deficient mice, we demonstrated that absence of these cytotoxic molecules
      resulted in reduced neural damage in myelin mutant mice. Our study strongly
      suggests that pathogenetically relevant immune reactions in proteolipid protein
      overexpressing mice are TCR-dependent and mediated by the classical components of
      CD8+ T-cell cytotoxicity, perforin, and Gzmb. These findings have high relevance
      with regard to our understanding of the pathogenesis of disorders primarily
      caused by genetically mediated oligodendropathy.

PMID- 20042680
TI  - Memantine improves cognition and reduces Alzheimer's-like neuropathology in
      transgenic mice.
AB  - Memantine is an N-methyl-d-aspartate receptor antagonist that is approved for the
      treatment of moderate to severe Alzheimer's disease (AD). In this study, three
      groups of triple-transgenic (3xTg-AD) mice with differing levels of AD-like
      pathology (6, 9, and 15 months of age) were treated for 3 months with doses of
      memantine equivalent to those used in humans. After the treatment, memantine
      treated mice had restored cognition and significantly reduced the levels of
      insoluble amyloid-beta (Abeta), Abeta dodecamers (Abeta*56), prefibrillar soluble
      oligomers, and fibrillar oligomers. The effects on pathology were stronger in
      older, more impaired animals. Memantine treatment also was associated with a
      decline in the levels of total tau and hyperphosphorylated tau. Finally,
      memantine pre-incubation prevented Abeta-induced inhibition of long-term
      potentiation in hippocampal slices of cognitively normal mice. These results
      suggest that the effects of memantine treatment on AD brain include disease
      modification and prevention of synaptic dysfunction.

PMID- 20042682
TI  - Influence of Hoxa5 on p53 tumorigenic outcome in mice.
AB  - Hox genes encode transcription factors of crucial importance in the pattern
      formation of a large spectrum of species. Several studies have now proposed a
      role for these developmental genes in cancer biology. It has been suggested that
      HOXA5 possesses growth-suppressive properties through activation of p53
      expression in human breast tissue. To assess the genetic cooperation that may
      exist between Hoxa5 and p53 in tumorigenesis, we generated Hoxa5/p53 compound
      mutant mice. The presence of Hoxa5 null alleles increased the susceptibility of
      p53(-/-) mice to develop tumors with a high prevalence for thymic lymphoma,
      suggesting that the loss of function of the two genes collaborate in tumor
      formation. To extend our analysis to mammary tumorigenesis, we performed
      Hoxa5/p53 whole mammary gland transplantations into wild-type hosts. In the p53(
      /-) background, the presence of one Hoxa5 mutant allele had no impact on mammary
      tumor formation. In contrast, the complete loss of Hoxa5 function influenced the
      tumorigenic outcome of p53(+/-) mammary glands. However, the collaborative nature
      of this interaction did not depend on the transcriptional regulation of p53 by
      Hoxa5. Altogether, our data establish that Hoxa5 and p53 cooperate in mammary
      tumorigenesis in vivo.

PMID- 20042683
TI  - Blockade of autoantibody-initiated tissue damage by using recombinant fab
      antibody fragments against pathogenic autoantigen.
AB  - Activation of the complement cascade via the classical pathway is required for
      the development of tissue injury in many autoantibody-mediated diseases. It
      therefore makes sense to block the pathological action of autoantibodies by
      preventing complement activation through inhibition of autoantibody binding to
      the corresponding pathogenic autoantigen using targeted Fab antibody fragments.
      To achieve this, we use bullous pemphigoid (BP) as an example of a typical
      autoimmune disease. Recombinant Fabs against the non-collagenous 16th-A domain of
      type XVII collagen, the main pathogenic epitope for autoantibodies in BP, were
      generated from antibody repertoires of BP patients by phage display. Two Fabs,
      Fab-B4 and Fab-19, showed marked ability to inhibit the binding of BP
      autoantibodies and subsequent complement activation in vitro. In the in vivo
      experiments using type XVII collagen humanized BP model mice, these Fabs
      protected mice against BP autoantibody-induced blistering disease. Thus, the
      blocking of pathogenic epitopes using engineered Fabs appears to demonstrate
      efficacy and may lead to disease-specific treatments for antibody-mediated
      autoimmune diseases.

PMID- 20042684
TI  - Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein
      synthesis and hypoxia-inducible factor-1-mediated gene expression.
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential
      role in regulating gene expression in response to hypoxia-ischemia. Ischemia
      causes the tissue not only to be hypoxic but also to be hypothermic because of
      the hypoperfusion under certain circumstances. On the other hand, the induced
      hypothermia is one of the most common therapeutic modalities to extend tolerance
      to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses
      at different organizational levels in the body, little is known about how hypoxia
      induced responses are affected by low temperature. We examined the influence of
      mild hypothermic conditions (28-32 degrees C) on HIF-1 in both in vitro and in
      vivo settings. In vitro experiments adopting cultured cells elucidated that
      hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low
      temperature. In contrast, exposure to the low temperature as long as 24 h
      suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes
      such as VEGF or GLUT-1. HIF-1alpha protein stability in the cell was not affected
      by hypothermic treatment. Furthermore, intracellular ATP content was reduced
      under 1% O(2) conditions but was not largely affected by hypothermic treatment.
      The evidence indicates that reduction of oxygen consumption is not largely
      involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA
      binding activity and HIF-1-dependent gene expressions induced under 10% O(2)
      atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic
      temperature but were inhibited under 5-h treatment. On the other hand, we
      indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity.
      In this report we describe for the first time that persisting low temperature
      significantly reduced HIF-1alpha neosynthesis under hypoxic conditions, leading
      to a decrease in gene expression for adaptation to hypoxia in both in vitro and
      in vivo settings.

PMID- 20042686
TI  - Follicle-stimulating hormone, interleukin-1, and bone density in adult women.
AB  - Recent studies have indicated that follicle-stimulating hormone (FSH) promotes
      bone loss. The present study tested the hypothesis that FSH enhances the activity
      of bone-resorbing cytokines [interleukin (IL)-1beta, tumor necrosis factor (TNF)
      alpha, and IL-6], either by inducing their secretion or by altering their
      receptor expression. Thirty-six women between the ages of 20 and 50 were assessed
      for bone mineral density (BMD), reproductive hormone, cytokine ligand and soluble
      receptor concentrations, and surface expression of cytokine receptors on
      monocytes. In addition, isolated mononuclear cells were incubated in vitro with
      exogenous FSH. Univariate regression analyses indicated that BMD was inversely
      related to serum FSH (r = -0.29 to -0.51, P = 0.03-0.001, depending upon the
      skeletal site). Physical activity and body composition were also identified as
      significant factors by multiple regressions. Exogenous FSH induced isolated cells
      to secrete IL-1beta, TNF-alpha, and IL-6 in proportion to the surface expression
      of FSH receptors on the monocytes. Endogenous (serum) FSH concentrations
      correlated with the circulating concentrations of these cytokines. None of these
      individual cytokines was related to BMD, but the IL-1beta to IL-1 receptor
      antagonist (IL-1Ra) ratio was inversely related to BMD (r = -0.53, P = 0.002) in
      all but the most physically active women, who had significantly lower expression
      of IL-1 type I receptors relative to type II (decoy receptors, P = 0.01).
      Physical activity also correlated positively with secretion of inhibitory soluble
      IL-1 receptors (r = 0.53, P = 0.003). Moreover, IL-1Ra correlated strongly with
      percent body fat (r = 0.66, P < 0.0001). These results indicate that BMD is
      related to FSH concentration, physical activity, and body composition. Although
      each of these factors likely has direct effects on bone, the present study
      suggests that each may also influence BMD by modulating the activity of the
      osteoresorptive cytokine IL-1beta.

PMID- 20042685
TI  - A SLC4-like anion exchanger from renal tubules of the mosquito (Aedes aegypti):
      evidence for a novel role of stellate cells in diuretic fluid secretion.
AB  - Transepithelial fluid secretion across the renal (Malpighian) tubule epithelium
      of the mosquito (Aedes aegypti) is energized by the vacuolar-type (V-type) H(+)
      ATPase and not the Na(+)-K(+)-ATPase. Located at the apical membrane of principal
      cells, the V-type H(+)-ATPase translocates protons from the cytoplasm to the
      tubule lumen. Secreted protons are likely to derive from metabolic H(2)CO(3),
      which raises questions about the handling of HCO(3)(-) by principal cells.
      Accordingly, we tested the hypothesis that a Cl/HCO(3) anion exchanger (AE)
      related to the solute-linked carrier 4 (SLC4) superfamily mediates the extrusion
      of HCO(3)(-) across the basal membrane of principal cells. We began by cloning
      from Aedes Malpighian tubules a full-length cDNA encoding an SLC4-like AE, termed
      AeAE. When expressed heterologously in Xenopus oocytes, AeAE is both N- and O
      glycosylated and mediates Na(+)-independent intracellular pH changes that are
      sensitive to extracellular Cl(-) concentration and to DIDS. In Aedes Malpighian
      tubules, AeAE is expressed as two distinct forms: one is O-glycosylated, and the
      other is N-glycosylated. Significantly, AeAE immunoreactivity localizes to the
      basal regions of stellate cells but not principal cells. Concentrations of DIDS
      that inhibit AeAE activity in Xenopus oocytes have no effects on the unstimulated
      rates of fluid secretion mediated by Malpighian tubules as measured by the Ramsay
      assay. However, in Malpighian tubules stimulated with kinin or calcitonin-like
      diuretic peptides, DIDS reduces the diuretic rates of fluid secretion to basal
      levels. In conclusion, Aedes Malpighian tubules express AeAE in the basal region
      of stellate cells, where this transporter may participate in producing diuretic
      rates of transepithelial fluid secretion.

PMID- 20042687
TI  - High-fat feeding alters the cardiovascular role of the hypothalamic
      paraventricular nucleus.
AB  - Increased sympathetic nerve activity is associated with obesity-related
      hypertension, but the underlying central neural mechanisms are not clear. We
      examined the role of the hypothalamic paraventricular nucleus (PVN) in the
      regulation of sympathetic nerve activity in rats fed a normal chow diet
      (controls) and rats fed a high-fat diet (36% fat) over 12 wk. The effects on
      blood pressure, heart rate, and lumbar sympathetic nerve activity (LSNA) induced
      by microinjection of the GABA(A) receptor agonist muscimol or the antagonist
      bicuculline were monitored in anesthetized rats. Body weight of rats fed the high
      fat diet was not significantly different from controls, but a significant 80%
      increase in epididymal fat mass, significantly elevated fasting blood glucose,
      and significantly impaired glucose tolerance were observed in rats fed the high
      fat diet. Resting blood pressure and heart rate were not significantly different
      between rats fed the high-fat diet and controls. Muscimol microinjected into the
      PVN elicited a greater reduction of blood pressure and LSNA in rats fed the high
      fat diet than controls: -14 +/- 6 vs. -7 +/- 2 mmHg and -35 +/- 6 vs. -10 +/- 9%
      (P < 0.05). Microinjection of bicuculline into the PVN increased blood pressure
      and LSNA, but the responses were similar in rats fed the high-fat diet and
      controls. In conclusion, the role of the paraventricular nucleus in
      cardiovascular regulation can be altered by a diet high in fat, even when
      hypertension and obesity are absent.

PMID- 20042688
TI  - Brain vasopressin V(1) receptors contribute to enhanced cardiovascular responses
      to acute stress in chronically stressed rats and rats with myocardial infarcton.
AB  - The present study was designed to determine the role of central vasopressin 1
      receptors (V(1)R) in the regulation of cardiovascular parameters in chronically
      stressed infarcted rats and sham-operated rats under resting conditions and
      during exposure to acute alarming stress. The experiments were performed on four
      groups of conscious sham-operated and four groups of infarcted rats subjected to
      intraventricular infusion of either vehicle or a V(1)R antagonist (V(1)RANT). Two
      groups of infarcted and two groups of sham-operated rats were subjected to mild
      chronic stressing. Mean arterial blood pressure (MABP) and heart rate (HR) were
      determined under resting conditions and after exposure to acute stress (air jet).
      During vehicle infusion, MABP and HR increases in response to acute stress in the
      infarcted rats not subjected to chronic stress, and in the infarcted and sham
      operated chronically stressed rats, were significantly greater than in the sham
      operated rats not exposed to chronic stress. However, MABP and HR responses to
      acute stress in the chronically stressed infarcted rats and chronically stressed
      sham-operated rats did not differ. V(1)RANT abolished differences in
      cardiovascular responses to acute stress between the experimental groups. Resting
      cardiovascular parameters were not affected by any of the experimental
      treatments. It is concluded that chronic stressing enhances the pressor and
      tachycardic responses to acute stress in the sham-operated rats but does not
      further intensify these responses in infarcted rats.The results provide evidence
      that central V(1)Rs are involved in potentiation of cardiovascular responses to
      acute stress in chronically stressed rats, infarcted rats, and chronically
      stressed infarcted rats.

PMID- 20042689
TI  - Physical exercise accelerates reentrainment of human sleep-wake cycle but not of
      plasma melatonin rhythm to 8-h phase-advanced sleep schedule.
AB  - Effects of timed physical exercise were examined on the reentrainment of sleep
      wake cycle and circadian rhythms to an 8-h phase-advanced sleep schedule.
      Seventeen male adults spent 12 days in a temporal isolation facility with dim
      light conditions (<10 lux). The sleep schedule was phase-advanced by 8 h from
      their habitual sleep times for 4 days, which was followed by a free-run session
      for 6 days, during which the subjects were deprived of time cues. During the
      shift schedule, the exercise group (n = 9) performed physical exercise with a
      bicycle ergometer in the early and middle waking period for 2 h each. The control
      group (n = 8) sat on a chair at those times. Their sleep-wake cycles were
      monitored every day by polysomnography and/or weight sensor equipped with a bed.
      The circadian rhythm in plasma melatonin was measured on the baseline day before
      phase shift: on the 4th day of shift schedule and the 5th day of free-run. As a
      result, the sleep-onset on the first day of free-run in the exercise group was
      significantly phase-advanced from that in the control and from the baseline. On
      the other hand, the circadian melatonin rhythm was significantly phase-delayed in
      the both groups, showing internal desynchronization of the circadian rhythms. The
      sleep-wake cycle resynchronized to the melatonin rhythm by either phase-advance
      or phase-delay shifts in the free-run session. These findings indicate that the
      reentrainment of the sleep-wake cycle to a phase-advanced schedule occurs
      independent of the circadian pacemaker and is accelerated by timed physical
      exercise.

PMID- 20042690
TI  - Cytochrome c oxidase is regulated by modulations in protein expression and
      mitochondrial membrane phospholipid composition in estivating African lungfish.
AB  - We examined some of the potential mechanisms lungfish (Protopterus dolloi) use to
      regulate cytochrome c oxidase (CCO), during metabolic depression. CCO activity
      was reduced by 67% in isolated liver mitochondria of estivating fish. This was
      likely accomplished, in part, by the 46% reduction in CCO subunit I protein
      expression in the liver. No change in the mRNA expression levels of CCO subunits
      I, II, III, and IV were found in the liver, suggesting CCO is under translational
      regulation; however, in the kidney, messenger limitation may be a factor as the
      expression of subunits I and II were depressed ( approximately 10-fold) during
      estivation, suggesting tissue-specific mechanisms of regulation. CCO is
      influenced by mitochondrial membrane phospholipids, particularly cardiolipin
      (CL). In P. dolloi, the phospholipid composition of the liver mitochondrial
      membrane changed during estivation, with a approximately 2.3-fold reduction in
      the amount of CL. Significant positive correlations were found between CCO
      activity and the amount of CL and phosphatidylethanolamine within the
      mitochondrial membrane. It appears CCO activity is regulated through multiple
      mechanisms in P. dolloi, and individual subunits of CCO are regulated
      independently, and in a tissue-specific manner. It is proposed that altering the
      amount of CL within the mitochondrial membrane may be a means of regulating CCO
      activity during metabolical depression in the African lungfish, P. dolloi.

PMID- 20042691
TI  - Influence of indomethacin on ventilatory and cerebrovascular responsiveness to
      CO2 and breathing stability: the influence of PCO2 gradients.
AB  - Indomethacin (INDO), a reversible cyclooxygenase inhibitor, is a useful tool for
      assessing the role of cerebrovascular reactivity on ventilatory control. Despite
      this, the effect of INDO on breathing stability during wakefulness has yet to be
      examined. Although the effect of reductions in cerebrovascular CO(2) reactivity
      on ventilatory CO(2) sensitivity is likely dependent upon the method used, no
      studies have compared the effect of INDO on steady-state and modified rebreathing
      estimates of ventilatory CO(2) sensitivity. The latter method includes the
      influence of PCO(2) gradients and cerebral perfusion, whereas the former does
      not. We examined the hypothesis that INDO-induced reduction in cerebrovascular
      CO(2) reactivity would 1) cause unstable breathing in conscious humans and 2)
      increase ventilatory CO(2) sensitivity during the steady-state method but not
      during rebreathing methods. We measured arterial blood gases, ventilation (VE),
      and middle cerebral artery velocity (MCAv) before and 90 min following INDO
      ingestion (100 mg) or placebo in 12 healthy participants. There were no changes
      in resting arterial blood gases or Ve following either intervention. INDO
      increased the magnitude of Ve variability (index of breathing stability) during
      spontaneous air breathing (+4.3 +/- 5.2 Deltal/min, P = 0.01) and reduced MCAv (
      25 +/- 19%, P < 0.01) and MCAv-CO(2) reactivity during steady-state (-47 +/- 27%,
      P < 0.01) and rebreathing (-32 +/- 25%, P < 0.01). The Ve-CO(2) sensitivity
      during the steady-state method was increased with INDO (+0.5 +/- 0.5 l x min(-1)
      x mmHg(-1), P < 0.01), while no changes were observed during rebreathing (P >
      0.05). These data indicate that the net effect of INDO on ventilatory control is
      an enhanced ventilatory loop gain resulting in increased breathing instability.
      Our findings also highlight important methodological and physiological
      considerations when assessing the effect of INDO on ventilatory CO(2)
      sensitivity, whereby the effect of INDO-induced reduction of cerebrovascular
      CO(2) reactivity on ventilatory CO(2) sensitivity is unmasked with the
      rebreathing method.

PMID- 20042692
TI  - Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension.
AB  - The bone morphogenetic protein (BMP) type 2 receptor ligand, Bmp2, is upregulated
      in the peripheral pulmonary vasculature during hypoxia-induced pulmonary
      hypertension (PH). This contrasts with the expression of Bmp4, which is expressed
      in respiratory epithelia throughout the lung. Unlike heterozygous null Bmp4 mice
      (Bmp4(LacZ/+)), which are protected from the development of hypoxic PH, mice that
      are heterozygous null for Bmp2 (Bmp2(+/-)) develop more severe hypoxic PH than
      their wild-type littermates. This is associated with reduced endothelial nitric
      oxide synthase (eNOS) expression and activity in the pulmonary vasculature of
      hypoxic Bmp2(+/-) but not Bmp4(LacZ/+) mutant mice. Furthermore, exogenous BMP2
      upregulates eNOS expression and activity in intrapulmonary artery and pulmonary
      endothelial cell preparations, indicating that eNOS is a target of Bmp2 signaling
      in the pulmonary vasculature. Together, these data demonstrate that Bmp2 and Bmp4
      exert opposing roles in hypoxic PH and suggest that the protective effects of
      Bmp2 are mediated by increasing eNOS expression and activity in the hypoxic
      pulmonary vasculature.

PMID- 20042693
TI  - Screening for common neurologic diseases among Israeli adolescents.
AB  - Neurologic disorders are the common causes of morbidity among adolescents. The
      estimated prevalence of common neurologic disorders relies on relatively small
      samples. We aimed to identify the prevalence of common neurologic disorders among
      Israeli adolescents. In Israel, all 17-year-old Israeli nationals are required to
      undergo a health-screening examination at the Israel Defense Forces recruiting
      office. Neurology specialists evaluate and classify suspected neurologic
      disorders. The findings included a high prevalence of neurologic morbidity among
      the 94 805 adolescents (61.5% males and 39.5% females) examined in 2001. The most
      prevalent diagnoses were headaches and learning disorders. The frequency of
      chronic headache in this study was relatively low. A significant difference in
      morbidity patterns between male and female adolescents was noted. Overall, we
      found that the prevalence of chronic, frequent headaches among adolescents is
      much lower than that reported previously. Headache, learning disability,
      epilepsy, and infectious or traumatic head injury were the most common diagnoses.

PMID- 20042694
TI  - Acute transient deafness representing a negative epileptic phenomenon.
AB  - We report herein 2 children who presented with acute deafness heralding an
      epileptic event manifesting thereafter by loss of consciousness and tonic
      generalized posturing, possibly reflecting a negative epileptic phenomenon. The
      first previously healthy male had 2 paroxysmal episodes 7 months apart, starting
      with acute deafness lasting for a few minutes followed by loss of consciousness
      and generalized tonic posturing for 10 minutes. Electroencephalography (EEG)
      during the second episodes demonstrated generalized epileptiform discharges. The
      second with previously controlled partial complex seizures presented with
      episodes of complete deafness lasting for a few minutes followed by loss of
      consciousness and focal tonic posturing lasting 10 minutes. Such acute deafness
      represented an aura of a focal seizure substantiated by right focal temporal
      epileptic discharges within the region of the primary auditory cortex. Therefore,
      EEG should be performed in any case of acute transient deafness, even in the
      absence of accompanying overt clinical seizures.

PMID- 20042699
TI  - Long-lasting synaptic potentiation induced by depolarization under conditions
      that eliminate detectable Ca2+ signals.
AB  - Activity-dependent alterations of synaptic transmission important for learning
      and memory are often induced by Ca(2+) signals generated by depolarization. While
      it is widely assumed that Ca(2+) is the essential transducer of depolarization
      into cellular plasticity, little effort has been made to test whether Ca(2+)
      independent responses to depolarization might also induce memory-like
      alterations. It was recently discovered that peripheral axons of nociceptive
      sensory neurons in Aplysia display long-lasting hyperexcitability triggered by
      conditioning depolarization in the absence of Ca(2+) entry (using nominally
      Ca(2+)-free solutions containing EGTA, "0Ca/EGTA") or the absence of detectable
      Ca(2+) transients (adding BAPTA-AM, "0Ca/EGTA/BAPTA-AM"). The current study
      reports that depolarization of central ganglia to approximately 0 mV for 2 min in
      these same solutions induced hyperexcitability lasting >1 h in sensory neuron
      processes near their synapses onto motor neurons. Furthermore, conditioning
      depolarization in these solutions produced a 2.5-fold increase in excitatory
      postsynaptic potential (EPSP) amplitude 1-3 h afterward despite a drop in motor
      neuron input resistance. Depolarization in 0 Ca/EGTA produced long-term
      potentiation (LTP) of the EPSP lasting > or = 1 days without changing
      postsynaptic input resistance. When re-exposed to extracellular Ca(2+) during
      synaptic tests, prior exposure to 0Ca/EGTA or to 0Ca/EGTA/BAPTA-AM decreased
      sensory neuron survival. However, differential effects on neuronal health are
      unlikely to explain the observed potentiation because conditioning depolarization
      in these solutions did not alter survival rates. These findings suggest that
      unrecognized Ca(2+)-independent signals can transduce depolarization into long
      lasting synaptic potentiation, perhaps contributing to persistent synaptic
      alterations following large, sustained depolarizations that occur during
      learning, neural injury, or seizures.

PMID- 20042700
TI  - Plantar cutaneous afferents normalize the reflex modulation patterns during
      stepping in chronic human spinal cord injury.
AB  - Plantar cutaneous afferent transmission is critical for recovery of locomotion in
      spinalized animals, whereas a phase-dependent reflex modulation is apparent
      during fictive or real locomotion. In nine people with a chronic spinal cord
      injury (SCI) the effects of foot sole stimulation on the soleus H-reflex and
      tibialis anterior (TA) flexion reflex modulation patterns during assisted
      stepping were established on different days. The soleus H-reflex was elicited by
      posterior tibial nerve stimulation followed by a supramaximal stimulus 100 ms
      after the test H-reflex to control for movement of recording electrodes. The
      flexion reflex was evoked by sural nerve stimulation with a 30-ms pulse train,
      recorded from the ipsilateral TA muscle, and elicited at 1.2- to twofold the
      reflex threshold. During assisted stepping, spinal reflexes were conditioned by
      percutaneous stimulation of the ipsilateral metatarsals at threefold perceptual
      threshold with a 20-ms pulse train delivered at 9- to 11-ms conditioning-test
      intervals. Stimuli were randomly dispersed across the step cycle, which was
      divided into 16 equal bins. The conditioned soleus H-reflex was significantly
      facilitated at midstance and depressed during midswing when compared with the
      unconditioned soleus H-reflex recorded during stepping. Foot sole stimulation
      induced a significant facilitation of the long-latency TA flexion reflex before,
      during, and after stance-to-swing transition when compared with the unconditioned
      long-latency TA flexion reflex during stepping. This study provides evidence that
      plantar cutaneous afferents remarkably influence the soleus H-reflex and TA
      flexion reflex modulation patterns during stepping and support that actions of
      plantar cutaneous afferents onto spinal interneuronal circuits engaged in
      locomotion are manifested in a phase-dependent manner in chronic SCI subjects.

PMID- 20042701
TI  - Frequency-velocity mismatch: a fundamental abnormality in parkinsonian gait.
AB  - Gait dysfunction and falling are major sources of disability for patients with
      advanced Parkinson's disease (PD). It is presently thought that the fundamental
      defect is an inability to generate normal stride length. Our data suggest,
      however, that the basic problem in PD gait is an impaired ability to match step
      frequency to walking velocity. In this study, foot movements of PD and normal
      subjects were monitored with an OPTOTRAK motion-detection system while they
      walked on a treadmill at different velocities. PD subjects were also paced with
      auditory stimuli at different frequencies. PD gait was characterized by step
      frequencies that were faster and stride lengths that were shorter than those of
      normal controls. At low walking velocities, PD stepping had a reduced or absent
      terminal toe lift, which truncated swing phases, producing shortened steps.
      Auditory pacing was not able to normalize step frequency at these lower
      velocities. Peak forward toe velocities increased with walking velocity and PD
      subjects could initiate appropriate foot dynamics during initial phases of the
      swing. They could not control the foot appropriately in terminal phases, however.
      Increased treadmill velocity, which matched the natural PD step frequency,
      generated a second toe lift, normalizing step size. Levodopa increased the
      bandwidth of step frequencies, but was not as effective as increases in walking
      velocity in normalizing gait. We postulate that the inability to control step
      frequency and adjust swing phase dynamics to slower walking velocities are major
      causes for the gait impairment in PD.

PMID- 20042702
TI  - Mode-locked spike trains in responses of ventral cochlear nucleus chopper and
      onset neurons to periodic stimuli.
AB  - We report evidence of mode-locking to the envelope of a periodic stimulus in
      chopper units of the ventral cochlear nucleus (VCN). Mode-locking is a
      generalized description of how responses in periodically forced nonlinear systems
      can be closely linked to the input envelope, while showing temporal patterns of
      higher order than seen during pure phase-locking. Re-analyzing a previously
      unpublished dataset in response to amplitude modulated tones, we find that of 55%
      of cells (6/11) demonstrated stochastic mode-locking in response to sinusoidally
      amplitude modulated (SAM) pure tones at 50% modulation depth. At 100% modulation
      depth SAM, most units (3/4) showed mode-locking. We use interspike interval (ISI)
      scattergrams to unravel the temporal structure present in chopper mode-locked
      responses. These responses compared well to a leaky integrate-and-fire model
      (LIF) model of chopper units. Thus the timing of spikes in chopper unit responses
      to periodic stimuli can be understood in terms of the complex dynamics of
      periodically forced nonlinear systems. A larger set of onset (33) and chopper
      units (24) of the VCN also shows mode-locked responses to steady-state vowels and
      cosine-phase harmonic complexes. However, while 80% of chopper responses to
      complex stimuli meet our criterion for the presence of mode-locking, only 40% of
      onset cells show similar complex-modes of spike patterns. We found a correlation
      between a unit's regularity and its tendency to display mode-locked spike trains
      as well as a correlation in the number of spikes per cycle and the presence of
      complex-modes of spike patterns. These spiking patterns are sensitive to the
      envelope as well as the fundamental frequency of complex sounds, suggesting that
      complex cell dynamics may play a role in encoding periodic stimuli and envelopes
      in the VCN.

PMID- 20042703
TI  - Utility of transcutaneous electrical nerve stimulation in neurologic pain
      disorders.

PMID- 20042705
TI  - Assessment: efficacy of transcutaneous electric nerve stimulation in the
      treatment of pain in neurologic disorders (an evidence-based review): report of
      the Therapeutics and Technology Assessment Subcommittee of the American Academy
      of Neurology.
AB  - OBJECTIVE: To determine if transcutaneous electric nerve stimulation (TENS) is
      efficacious in the treatment of pain in neurologic disorders. METHODS: We
      performed a systematic literature search of Medline and the Cochrane Library from
      inception to April 2009. RESULTS: There are conflicting reports of TENS compared
      to sham TENS in the treatment of chronic low back pain, with 2 Class II studies
      showing benefit, but 2 Class I studies and another Class II study not showing
      benefit. Because the Class I studies are stronger evidence, TENS is established
      as ineffective for the treatment of chronic low back pain (2 Class I studies).
      TENS is probably effective in treating painful diabetic neuropathy (2 Class II
      studies). RECOMMENDATIONS: Transcutaneous electric nerve stimulation (TENS) is
      not recommended for the treatment of chronic low back pain (Level A). TENS should
      be considered in the treatment of painful diabetic neuropathy (Level B). Further
      research into the mechanism of action of TENS is needed, as well as more rigorous
      studies for determination of efficacy.

PMID- 20042704
TI  - Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization.
AB  - BACKGROUND: Neuroimaging measures and chemical biomarkers may be important
      indices of clinical progression in normal aging and mild cognitive impairment
      (MCI) and need to be evaluated longitudinally. OBJECTIVE: To characterize cross
      sectionally and longitudinally clinical measures in normal controls, subjects
      with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment
      of the utility of neuroimaging and chemical biomarker measures. METHODS: A total
      of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were
      enrolled at baseline and followed for 12 months using standard cognitive and
      functional measures typical of clinical trials. RESULTS: The subjects with MCI
      were more memory impaired than the cognitively normal subjects but not as
      impaired as the subjects with AD. Nonmemory cognitive measures were only
      minimally impaired in the subjects with MCI. The subjects with MCI progressed to
      dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the
      subjects with MCI were on antidementia therapies. There was minimal movement on
      the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal
      control subjects, slight movement for the subjects with MCI of 1.1, and a modest
      change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42
      separated the 3 groups as expected and successfully predicted the 12-month change
      in cognitive measures. CONCLUSION: The Alzheimer's Disease Neuroimaging
      Initiative has successfully recruited cohorts of cognitively normal subjects,
      subjects with mild cognitive impairment (MCI), and subjects with Alzheimer
      disease with anticipated baseline characteristics. The 12-month progression rate
      of MCI was as predicted, and the CSF measures heralded progression of clinical
      measures over 12 months.

PMID- 20042707
TI  - Hyaluronic Acid binding protein 2 is a novel regulator of vascular integrity.
AB  - OBJECTIVE: The disruption of the endothelial cell barrier is a critical feature
      of inflammation and an important contributing factor to acute lung injury (ALI),
      an inflammatory condition that is a major cause of morbidity and mortality in
      critically ill patients. We evaluated the role of the extracellular serine
      protease, hyaluronic acid binding protein 2 (HABP2), in vascular barrier
      regulation. METHODS AND RESULTS: By using immunoblot and immunohistochemical
      analysis, we observed that lipopolysaccharide (LPS) induces HABP2 expression in
      murine lung endothelium in vivo and in human pulmonary microvascular endothelial
      cells (ECs) in vitro. High-molecular-weight hyaluronan (HMW-HA, approximately
      1x10(6) Da) decreased HABP2 protein expression in human pulmonary microvascular
      ECs and decreased purified HABP2 enzymatic activity, whereas low-molecular-weight
      HA (LMW-HA, approximately 2500 Da) increased these activities. The effects of LMW
      HA, but not HMW-HA, on HABP2 activity were inhibited with a peptide of the
      polyanion-binding domain of HABP2. Silencing (small interfering RNA) HABP2
      expression augmented HMW-HA-induced EC barrier enhancement and inhibited LPS and
      LMW-HA-mediated EC barrier disruption, results that were reversed with
      overexpression of HABP2. Silencing protease-activated receptor 1 and 3, RhoA, or
      Rho kinase expression attenuated LPS-, LMW-HA-, and HABP2-mediated EC barrier
      disruption. By using murine models of acute lung injury, we observed that LPS-
      and ventilator-induced pulmonary vascular hyperpermeability was significantly
      reduced with vascular silencing (small interfering RNA) of HABP2. CONCLUSIONS:
      HABP2 negatively regulates vascular integrity via activation of protease
      activated receptor/RhoA/Rho kinase signaling and represents a potentially useful
      therapeutic target for syndromes of increased vascular permeability.

PMID- 20042706
TI  - BMPER is upregulated by statins and modulates endothelial inflammation by
      intercellular adhesion molecule-1.
AB  - OBJECTIVE: In addition to lowering cholesterol, statins exert pleiotropic effects
      on endothelial cells. Bone morphogenetic proteins (BMPs) have recently been
      implicated in vascular inflammation and disease. We set out to investigate the
      effect of statins on BMP endothelial cell precursor-derived regulator (BMPER), a
      novel member of the BMP pathway. METHODS AND RESULTS: Mevastatin enhanced BMPER
      expression in cultured endothelial cells in a time- and concentration-dependent
      manner as determined by immunocytochemistry, RT-PCR, and Western blotting.
      Similar effects were observed in vitro and in vivo using simvastatin. Actinomycin
      D chase analysis and BMPER promoter reporter assays revealed that this is mostly
      a posttranscriptional event resulting in prolonged BMPER RNA half-life. We
      confirmed that the RhoA/Rho-associated coiled-coil containing protein kinase Rho
      kinase (Rock)/actin pathway is involved using the specific pathway activator
      cytotoxic necrotizing factor of Yersinia pseudotuberculosis, which prevented
      upregulation of BMPER expression by mevastatin and pathway inhibitors (C3-toxin,
      RhoAN19 mutant, fasudil, and cytochalasin D) that enhanced BMPER expression.
      Increasing concentrations of BMPER exert antiinflammatory features in endothelial
      cells as reflected by intercellular adhesion molecule-1 downregulation.
      Accordingly, silencing of BMPER enhances intercellular adhesion molecule-1
      expression. Furthermore, mevastatin reduced the expression of proinflammatory
      BMP4, a well-known direct interaction partner of BMPER. CONCLUSIONS: Mevastatin
      modulates the BMP pathway by enhancing BMPER via the RhoA/Rock/actin pathway, as
      well as by reducing BMP4 expression. BMP4 downregulation and BMPER upregulation
      contribute to the antiinflammatory pleiotropic effects of statins.

PMID- 20042708
TI  - Diabetes mellitus induces bone marrow microangiopathy.
AB  - OBJECTIVE: The impact of diabetes on the bone marrow (BM) microenvironment was
      not adequately explored. We investigated whether diabetes induces microvascular
      remodeling with negative consequence for BM homeostasis. METHODS AND RESULTS: We
      found profound structural alterations in BM from mice with type 1 diabetes with
      depletion of the hematopoietic component and fatty degeneration. Blood flow
      (fluorescent microspheres) and microvascular density (immunohistochemistry) were
      remarkably reduced. Flow cytometry verified the depletion of MECA-32(+)
      endothelial cells. Cultured endothelial cells from BM of diabetic mice showed
      higher levels of oxidative stress, increased activity of the senescence marker
      beta-galactosidase, reduced migratory and network-formation capacities, and
      increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry
      analysis of lineage(-) c-Kit(+) Sca-1(+) cell distribution along an in vivo
      Hoechst-33342 dye perfusion gradient documented that diabetes depletes lineage(-)
      c-Kit(+) Sca-1(+) cells predominantly in the low-perfused part of the marrow.
      Cell depletion was associated to increased oxidative stress, DNA damage, and
      activation of apoptosis. Boosting the antioxidative pentose phosphate pathway by
      benfotiamine supplementation prevented microangiopathy, hypoperfusion, and
      lineage(-) c-Kit(+) Sca-1(+) cell depletion. CONCLUSIONS: We provide novel
      evidence for the presence of microangiopathy impinging on the integrity of
      diabetic BM. These discoveries offer the framework for mechanistic solutions of
      BM dysfunction in diabetes.

PMID- 20042709
TI  - Spontaneous adult-onset pulmonary arterial hypertension attributable to increased
      endothelial oxidative stress in a murine model of hereditary hemorrhagic
      telangiectasia.
AB  - OBJECTIVE: Loss-of-function mutations in genes coding for transforming growth
      factor-beta/bone morphogenetic protein receptors and changes in nitric oxide(*)
      (NO(*)) bioavailability are associated with hereditary hemorrhagic telangiectasia
      and some forms of pulmonary arterial hypertension. How these abnormalities lead
      to seemingly disparate pulmonary pathologies remains unknown. Endoglin (Eng), a
      transforming growth factor-beta coreceptor, is mutated in hereditary hemorrhagic
      telangiectasia and involved in regulating endothelial NO(*) synthase (eNOS)
      derived NO(*) production and oxidative stress. Because some patients with
      pulmonary arterial hypertension harbor ENG mutations leading to haplo
      insufficiency, we investigated the pulmonary vasculature of Eng(+/-) mice and the
      potential contribution of abnormal eNOS activation to pulmonary arterial
      hypertension. METHODS AND RESULTS: Hemodynamic, histological, and biochemical
      assessments and x-ray micro-CT imaging of adult Eng(+/-) mice indicated signs of
      pulmonary arterial hypertension including increased right ventricular systolic
      pressure, degeneration of the distal pulmonary vasculature, and muscularization
      of small arteries. These findings were absent in 3-week-old Eng(+/-) mice and
      were attributable to constitutively uncoupled eNOS activity in the pulmonary
      circulation, as evidenced by reduced eNOS/heat shock protein 90 association and
      increased eNOS-derived superoxide ((*)O(2)(-)) production in a BH(4)-independent
      manner. These changes render eNOS unresponsive to regulation by transforming
      growth factor-beta/bone morphogenetic protein and underlie the signs of pulmonary
      arterial hypertension that were prevented by Tempol. CONCLUSIONS: Adult Eng(+/-)
      mice acquire signs of pulmonary arterial hypertension that are attributable to
      uncoupled eNOS activity and increased (*)O(2)(-) production, which can be
      prevented by antioxidant treatment. Eng links transforming growth factor/bone
      morphogenetic protein receptors to the eNOS activation complex, and its reduction
      in the pulmonary vasculature leads to increased oxidative stress and pulmonary
      arterial hypertension.

PMID- 20042710
TI  - Platelets and megakaryocytes contain functional nuclear factor-kappaB.
AB  - OBJECTIVE: To investigate the presence and role of NF-kappaB proteins in
      megakaryocytes and platelets. The nuclear factor-kappaB (NF-kappaB) transcription
      factor family is well known for its role in eliciting inflammation and promoting
      cell survival. We discovered that human megakaryocytes and platelets express the
      majority of NF-kappaB family members, including the regulatory inhibitor-kappaB
      (I-kappaB) and I-kappa kinase (IKK) molecules. METHODS AND RESULTS: Anucleate
      platelets exposed to NF-kappaB inhibitors demonstrated impaired fundamental
      functions involved in repairing vascular injury and thrombus formation.
      Specifically, NF-kappaB inhibition diminished lamellapodia formation, decreased
      clot retraction times, and reduced thrombus stability. Moreover, inhibition of I
      kappaB-alpha phosphorylation (BAY-11-7082) reverted fully spread platelets back
      to a spheroid morphology. Addition of recombinant IKK-beta or I-kappaB-alpha
      protein to BAY inhibitor-treated platelets partially restored platelet spreading
      in I-kappaB-alpha inhibited platelets, and addition of active IKK-beta increased
      endogenous I-kappaB-alpha phosphorylation levels. CONCLUSIONS: These novel
      findings support a crucial and nonclassical role for the NF-kappaB family in
      modulating platelet function and reveal that platelets are sensitive to NF-kappaB
      inhibitors. As NF-kappaB inhibitors are being developed as antiinflammatory and
      anticancer agents, they may have unintended effects on platelets. On the basis of
      these data, NF-kappaB is also identified as a new target to dampen unwanted
      platelet activation.

PMID- 20042711
TI  - Long-term cigarette smoke exposure in a mouse model of ciliated epithelial cell
      function.
AB  - Exposure to cigarette smoke is associated with airway epithelial mucus cell
      hyperplasia and a decrease in cilia and ciliated cells. Few models have addressed
      the long-term effects of chronic cigarette smoke exposure on ciliated epithelial
      cells. Our previous in vitro studies showed that cigarette smoke decreases
      ciliary beat frequency (CBF) via the activation of protein kinase C (PKC). We
      hypothesized that chronic cigarette smoke exposure in an in vivo model would
      decrease airway epithelial cell ciliary beating in a PKC-dependent manner. We
      exposed C57BL/6 mice to whole-body cigarette smoke 2 hours/day, 5 days/week for
      up to 1 year. Tracheal epithelial cell CBF and the number of motile cells were
      measured after necropsy in cut tracheal rings, using high-speed digital video
      microscopy. Tracheal epithelial PKC was assayed according to direct kinase
      activity. At 6 weeks and 3 months of smoke exposure, the baseline CBF was
      slightly elevated (~1 Hz) versus control mice, with no change in beta-agonist
      stimulated CBF between control mice and cigarette smoke-exposed mice. By 6 months
      of smoke exposure, the baseline CBF was significantly decreased (2-3 Hz) versus
      control mice, and a beta-agonist failed to stimulate increased CBF. The loss of
      beta-agonist-increased CBF continued at 9 months and 12 months of smoke exposure,
      and the baseline CBF was significantly decreased to less than one third of the
      control rate. In addition to CBF, ciliated cell numbers significantly decreased
      in response to smoke over time, with a significant loss of tracheal ciliated
      cells occurring between 6 and 12 months. In parallel with the slowing of CBF,
      significant PKC activation from cytosol to the membrane of tracheal epithelial
      cells was detected in mice exposed to smoke for 6-12 months.

PMID- 20042712
TI  - Activation of the cystic fibrosis transmembrane conductance regulator by the
      flavonoid quercetin: potential use as a biomarker of DeltaF508 cystic fibrosis
      transmembrane conductance regulator rescue.
AB  - Therapies to correct the DeltaF508 cystic fibrosis transmembrane conductance
      regulator (CFTR) folding defect require sensitive methods to detect channel
      activity in vivo. The beta2 adrenergic receptor agonists, which provide the CFTR
      stimuli commonly used in nasal potential difference assays, may not overcome the
      channel gating defects seen in DeltaF508 CFTR after plasma membrane localization.
      In this study, we identify an agent, quercetin, that enhances the detection of
      surface DeltaF508 CFTR, and is suitable for nasal perfusion. A screen of
      flavonoids in CFBE41o- cells stably transduced with DeltaF508 CFTR, corrected to
      the cell surface with low temperature growth, revealed that quercetin stimulated
      an increase in the short-circuit current. This increase was dose-dependent in
      both Fisher rat thyroid and CFBE41o- cells. High concentrations inhibited Cl-
      conductance. In CFBE41o- airway cells, quercetin (20 MUg/ml) activated DeltaF508
      CFTR, whereas the beta2 adrenergic receptor agonist isoproterenol did not.
      Quercetin had limited effects on cAMP levels, but did not produce detectable
      phosphorylation of the isolated CFTR R-domain, suggesting an activation
      independent of channel phosphorylation. When perfused in the nares of Cftr(+)
      mice, quercetin (20 MUg/ml) produced a hyperpolarization of the potential
      difference that was absent in Cftr(-/-) mice. Finally, quercetin-induced, dose
      dependent hyperpolarization of the nasal potential difference was also seen in
      normal human subjects. Quercetin activates CFTR-mediated anion transport in
      respiratory epithelia in vitro and in vivo, and may be useful in studies intended
      to detect the rescue of DeltaF508 CFTR by nasal potential difference.

PMID- 20042713
TI  - Reduced viability of mice with lung epithelial-specific knockout of
      glucocorticoid receptor.
AB  - Glucocorticoid (GC)-responsive epithelial-mesenchymal interactions regulate lung
      development. The GC receptor (GR) mediates GC signaling. Mice lacking GR in all
      tissues die at birth of respiratory failure. To determine the specific need for
      epithelial GR in lung development, we bred triple transgenic mice that carry
      SPC/rtTA, tet-O-Cre, and floxed, but not wild-type, GR genes. When exposed to
      doxycycline in utero, triple transgenic (GRepi-) mice exhibit a Cre-mediated
      recombination event that inactivates the floxed GR gene in airway epithelial
      cells. Immunofluorescence confirmed the elimination of GR in Cre-positive airway
      epithelial cells of late gestation GRepi- mice. Embryonic Day 18.5 pups had a
      relatively immature appearance with increased lung cellularity and increased
      pools of glycogen in the epithelium. Postnatal Day 0.5 pups had decreased
      viability. We used quantitative RT-PCR to demonstrate that specific elimination
      of epithelial immunoreactive GR in GRepi- mice is associated with reduced mRNA
      expression for surfactant proteins (SPs) A, B, C, and D; beta- and gamma-ENaC;
      T1alpha; the 10-kD Clara cell protein (CCSP); and aquaporin 5 (AQP5). Western
      blots confirmed reduced levels of AQP5 protein. No reduction in the levels of the
      GR transport protein importin (IPO)-13 was observed. Our findings demonstrate a
      requirement for lung epithelial cell GR in normal lung development. We speculate
      that impaired epithelial differentiation, leading to decreased SPs,
      transepithelial Na, and liquid absorption at birth, may contribute to the reduced
      survival of newborn mice with suppressed lung epithelial GR.

PMID- 20042714
TI  - The loss of tuberin promotes cell invasion through the beta-catenin pathway.
AB  - Mutations in the tumor suppressor tuberin (TSC2) are a common factor in the
      development of lymphangioleiomyomatosis (LAM). LAM is a cystic lung disease that
      is characterized by the infiltration of smooth muscle-like cells into the
      pulmonary parenchyma. The mechanism by which the loss of tuberin promotes the
      development of LAM has yet to be elucidated, although several lines of evidence
      suggest it is due to the metastasis of tuberin-deficient cells. Here we show that
      tuberin-null cells become nonadherent and invasive. These nonadherent cells
      express cleaved forms of beta-catenin. In reporter assays, the beta-catenin
      products are transcriptionally active and promote MMP7 expression. Invasion by
      the tuberin-null cells is mediated by MMP7. Examination of LAM tissues shows the
      expression of cleaved beta-catenin products and MMP7 consistent with a model that
      tuberin-deficient cells acquire invasive properties through a beta-catenin
      dependent mechanism, which may underlie the development of LAM.

PMID- 20042716
TI  - Protection from right- and left-sided colorectal neoplasms after colonoscopy:
      population-based study.
AB  - BACKGROUND: Colonoscopy is used for early detection and prevention of colorectal
      cancer, but evidence on the magnitude of overall protection and protection
      according to anatomical site through colonoscopy performed in the community
      setting is sparse. We assessed whether receiving a colonoscopy in the preceding
      10-year period, compared with no colonoscopy, was associated with prevalence of
      advanced colorectal neoplasms (defined as cancers or advanced adenomas) at
      various anatomical sites. METHODS: A statewide cross-sectional study was
      conducted among 3287 participants in screening colonoscopy between May 1, 2005,
      and December 31, 2007, from the state of Saarland in Germany who were aged 55
      years or older. Prevalence of advanced colorectal neoplasms was ascertained by
      screening colonoscopy and histopathologic examination of any polyps excised.
      Previous colonoscopy history was obtained by standardized questionnaire, and its
      association with prevalence of advanced colorectal neoplasms was estimated, after
      adjustment for potential confounding factors by log-binomial regression. RESULTS:
      Advanced colorectal neoplasms were detected in 308 (11.4%) of the 2701
      participants with no previous colonoscopy compared with 36 (6.1%) of the 586
      participants who had undergone colonoscopy within the preceding 10 years. After
      adjustment, overall and site-specific adjusted prevalence ratios for previous
      colonoscopy in the previous 10-year period were as follows: overall, 0.52 (95%
      confidence interval [CI] = 0.37 to 0.73); cecum and ascending colon, 0.99 (95% CI
      = 0.50 to 1.97); hepatic flexure and transverse colon, 1.21 (95% CI = 0.60 to
      2.42); right-sided colon combined (cecum to transverse colon), 1.05 (95% CI =
      0.63 to 1.76); splenic flexure and descending colon, 0.36 (95% CI = 0.16 to
      0.82); sigmoid colon, 0.29 (95% CI = 0.16 to 0.53); rectum, 0.07 (95% CI = 0.02
      to 0.40); left colon and rectum combined (splenic flexure to rectum, referred to
      as left-sided elsewhere), 0.33 (95% CI = 0.21 to 0.53). CONCLUSION: Prevalence of
      left-sided advanced colorectal neoplasms, but not right-sided advanced neoplasms,
      was strongly reduced within a 10-year period after colonoscopy, even in the
      community setting.

PMID- 20042715
TI  - Assessing lead time of selected ovarian cancer biomarkers: a nested case-control
      study.
AB  - BACKGROUND: CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy
      receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer
      biomarkers. Except for CA125, their behavior in the prediagnostic period has not
      been evaluated. METHODS: Immunoassays were used to determine concentrations of
      CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic
      serum specimens (1-11 samples per participant) that were contributed 0-18 years
      before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with
      advanced-stage serous carcinoma) and during a comparable time interval before the
      reference date from 70 matched control subjects who were participating in the
      Carotene and Retinol Efficacy Trial. Lowess curves were fit to biomarker levels
      in cancer patients and control subjects separately to summarize mean levels over
      time. Receiver operating characteristic curves were plotted, and area-under-the
      curve (AUC) statistics were computed to summarize the discrimination ability of
      these biomarkers by time before diagnosis. RESULTS: Smoothed mean concentrations
      of CA125, HE4, and mesothelin (but not of B7-H4, DcR3, and spondin-2) began to
      increase (visually) in cancer patients relative to control subjects approximately
      3 years before diagnosis but reached detectable elevations only within the final
      year before diagnosis. In descriptive receiver operating characteristic analyses,
      the discriminatory power of these biomarkers was limited (AUC statistics range =
      0.56-0.75) but showed increasing accuracy with time approaching diagnosis (eg,
      AUC statistics for CA125 were 0.57, 0.68, and 0.74 for > or = 4, 2-4, and <2
      years before diagnosis, respectively). CONCLUSION: Serum concentrations of CA125,
      HE4, and mesothelin may provide evidence of ovarian cancer 3 years before
      clinical diagnosis, but the likely lead time associated with these markers
      appears to be less than 1 year.

PMID- 20042717
TI  - Is the effectiveness of colonoscopy "good enough" for population-based screening?

PMID- 20042718
TI  - Designing early detection programs for ovarian cancer.

PMID- 20042719
TI  - Re: Population-based study of peritumoral lymphovascular invasion and outcome
      among patients with operable breast cancer.

PMID- 20042721
TI  - Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor
      acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers?
AB  - Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus
      define common subgroups of B-cell lymphoma but are rare in B-cell precursor acute
      lymphoblastic leukemia (BCP-ALL). Recent fluorescent in situ hybridization and
      molecular cloning studies have identified several novel IGH translocations
      involving genes that play important roles in normal hemopoiesis, including the
      cytokine receptor genes CRLF2 and EPOR, all members of the CCAAT enhancer-binding
      protein gene family, as well as genes not normally expressed in hemopoietic cells
      including inhibitor of DNA binding 4. IGH translocation results in deregulated
      target gene expression because of juxtaposition with IGH transcriptional
      enhancers. However, many genes targeted by IGH translocations are also more
      commonly deregulated in BCP-ALL as a consequence of other genetic or epigenetic
      mechanisms. For example, interstitial genomic deletions also result in
      deregulated CRLF2 expression, whereas EPOR expression is deregulated as a
      consequence of the ETV6-RUNX1 fusion. The possible clinical importance of many of
      the various IGH translocations in BCP-ALL remains to be determined from
      prospective studies, but CRLF2 expression is associated with a poor prognosis.
      Despite their rarity, IGH chromosomal translocations in BCP-ALL therefore define
      not only new mechanisms of B-cell transformation but also clinically important
      subgroups of disease and suggest new targeted therapeutic approaches.

PMID- 20042720
TI  - Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5
      and mediates expression of KLF2 and eNOS.
AB  - Fluid shear stress generated by steady laminar blood flow protects vessels from
      atherosclerosis. Kruppel-like factor 2 (KLF2) and endothelial nitric oxide
      synthase (eNOS) are fluid shear stress-responsive genes and key mediators in flow
      anti-inflammatory and antiatherosclerotic actions. However, the molecular
      mechanisms underlying flow induction of KLF2 and eNOS remain largely unknown.
      Here, we show a novel role of histone deacetylase 5 (HDAC5) in flow-mediated KLF2
      and eNOS expression. We found for the first time that fluid shear stress
      stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through
      a calcium/calmodulin-dependent pathway. Consequently, flow induced the
      dissociation of HDAC5 and myocyte enhancer factor-2 (MEF2) and enhanced MEF2
      transcriptional activity, which leads to expression of KLF2 and eNOS. Adenoviral
      overexpression of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 were
      replaced by Ala259/Ala498, HDAC5-S/A), which shows resistance to flow-induced
      nuclear export, suppressed flow-mediated MEF2 transcriptional activity and
      expression of KLF2 and eNOS. Importantly, HDAC5-S/A attenuated the flow
      inhibitory effect on monocyte adhesion to endothelial cells. Taken together, our
      results reveal that phosphorylation-dependent derepression of HDAC5 mediates flow
      induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest
      that HDAC5 could be a potential therapeutic target for the prevention of
      atherosclerosis.

PMID- 20042722
TI  - Akt1 and Akt2 promote peripheral B-cell maturation and survival.
AB  - Although the 3 isoforms of Akt regulate cell growth, proliferation, and survival
      in a wide variety of cell types, their role in B-cell development is unknown. We
      assessed B-cell maturation in the bone marrow (BM) and periphery in chimeras
      established with fetal liver progenitors lacking Akt1 and/or Akt2. We found that
      the generation of marginal zone (MZ) and B1 B cells, 2 key sources of
      antibacterial antibodies, was highly dependent on the combined expression of Akt1
      and Akt2. In contrast, Akt1/2 deficiency did not negatively affect the generation
      of transitional or mature follicular B cells in the periphery or their precursors
      in the BM. However, Akt1/2-deficient follicular B cells exhibited a profound
      survival defect when forced to compete against wild-type B cells in vivo.
      Altogether, these studies show that Akt signaling plays a key role in peripheral
      B-cell maturation and survival.

PMID- 20042723
TI  - Dengue virus-induced hemorrhage in a nonhuman primate model.
AB  - Lack of a dengue hemorrhagic animal model recapitulating human dengue virus
      infection has been a significant impediment in advancing our understanding of the
      early events involved in the pathogenesis of dengue disease. In efforts to
      address this issue, a group of rhesus macaques were intravenously infected with
      dengue virus serotype 2 (strain 16 681) at 1 x 10(7) PFU/animal. A classic dengue
      hemorrhage developed 3 to 5 days after infection in 6 of 6 animals. Blood
      chemistry appeared to be normal with exception of creatine phosphokinase, which
      peaked at 7 days after infection. A modest thrombocytopenia and noticeable
      neutropenia concomitant with slight decrease of hemoglobin and hematocrit were
      registered. In addition, the concentration of D-dimer was elevated significantly.
      Viremia peaked at 3 to 5 days after infection followed by an inverse relationship
      between T and B lymphocytes and a bimodal pattern for platelet-monocytes and
      platelet-neutrophil aggregates. Dengue virus containing platelets engulfed by
      monocytes was noted at 8 or 9 days after infection. Thus, rhesus macaques
      inoculated intravenously with a high dose of dengue virus produced dengue
      hemorrhage, which may provide a unique platform to define the early events in
      dengue virus infection and help identify which blood components contribute to the
      pathogenesis of dengue disease.

PMID- 20042724
TI  - Molecular characterization of in-frame and out-of-frame alternative splicings in
      coagulation factor XI pre-mRNA.
AB  - Alternative splicing of pre-mRNAs is a central process to the generation of
      proteome complexity. However, many alternative mRNA isoforms carry premature
      termination codons (PTCs) rendering them possible targets for the nonsense
      mediated mRNA decay (NMD) pathway. The F11 gene consists of 15 exons spanning
      approximately 23 kb on chromosome 4q35 and codes for coagulation factor XI (FXI),
      a 160-kDa dimeric zymogen composed of 4 apple domains and a serine protease
      domain. Here, we characterized the F11 splicing pattern in human liver and
      platelets identifying multiple in-frame and out-of-frame splicing events.
      Inhibition of NMD resulted in the up-regulation of all unproductively spliced F11
      transcripts, thus providing evidence that these PTC-containing mRNAs are under
      the control of NMD. Among in-frame alternatively spliced transcripts, the one
      skipping exons 6 and 7 would lead to the synthesis of a FXI protein lacking 1
      apple domain (FXI-Delta6/7). Ex vivo expression in mammalian cells demonstrated
      that FXI-Delta6/7 is mostly retained intracellularly, and secreted only in low
      amounts. Traces of this FXI isoform were detectable in human plasma. Our results
      suggest that the coupling of alternative splicing and NMD may play a role in
      regulating F11 expression, and point to the existence of a novel FXI isoform.

PMID- 20042725
TI  - Induction of tolerance to bone marrow allografts by donor-derived host
      nonreactive ex vivo-induced central memory CD8 T cells.
AB  - Enabling engraftment of allogeneic T cell-depleted bone marrow (TDBM) under
      reduced-intensity conditioning represents a major challenge in bone marrow
      transplantation (BMT). Anti-third-party cytotoxic T lymphocytes (CTLs) were
      previously shown to be endowed with marked ability to delete host antidonor T
      cells in vitro, but were found to be less effective in vivo. This could result
      from diminished lymph node (LN) homing caused by the prolonged activation, which
      induces a CD44(+)CD62L(-) effector phenotype, and thereby prevents effective
      colocalization with, and neutralization of, alloreactive host T cells (HTCs). In
      the present study, LN homing, determined by imaging, was enhanced upon culture
      conditions that favor the acquisition of CD44(+)CD62L(+) central memory cell
      (Tcm) phenotype by anti-third-party CD8(+) cells. These Tcm-like cells displayed
      strong proliferation and prolonged persistence in BM transplant recipients.
      Importantly, adoptively transferred HTCs bearing a transgenic T-cell receptor
      (TCR) with antidonor specificity were efficiently deleted only by donor-type
      Tcms. All these attributes were found to be associated with improved efficacy in
      overcoming T cell-mediated rejection of TDBM, thereby enabling high survival rate
      and long-term donor chimerism, without causing graft-versus-host disease. In
      conclusion, anti-third-party Tcms, which home to recipient LNs and effectively
      delete antidonor T cells, could provide an effective and novel tool for
      overcoming rejection of BM allografts.

PMID- 20042726
TI  - Verification of the susceptibility loci on 7p12.2, 10q21.2, and 14q11.2 in
      precursor B-cell acute lymphoblastic leukemia of childhood.
AB  - Recent genome-wide association data have implicated genetic variation at 7p12.2
      (IKZF1), 10q21.2 (ARIDB5), and 14q11.2 (CEBPE) in the etiology of B-cell
      childhood acute lymphoblastic leukemia (ALL). To verify and further examine the
      relationship between these variants and ALL risk, we genotyped 1384 cases of
      precursor B-cell childhood ALL and 1877 controls from Germany and the United
      Kingdom. The combined data provided statistically significant support for an
      association between genotype at each of these loci and ALL risk; odds ratios
      (OR), 1.69 (P = 7.51 x10(-22)), 1.80 (P = 5.90 x 10(-28)), and 1.27 (P = 4.90 x
      10(-6)), respectively. Furthermore, the risk of ALL increases with an increasing
      numbers of variant alleles for the 3 loci (OR(per-allele) = 1.53, 95% confidence
      interval, 1.44-1.62; P(trend) = 3.49 x 10(-42)), consistent with a polygenic
      model of disease susceptibility. These data provide unambiguous evidence for the
      role of these variants in defining ALL risk underscoring approximately 64% of
      cases.

PMID- 20042727
TI  - Graft-versus-host disease: regulation by microbe-associated molecules and innate
      immune receptors.
AB  - Acute graft-versus-host disease (GVHD) remains the major obstacle to a more
      favorable therapeutic outcome of allogeneic hematopoietic stem cell
      transplantation (HSCT). GVHD is characterized by tissue damage in gut, liver, and
      skin, caused by donor T cells that are critical for antitumor and antimicrobial
      immunity after HSCT. One obstacle in combating GVHD used to be the lack of
      understanding the molecular mechanisms that are involved in the initiation phase
      of this syndrome. Recent research has demonstrated that interactions between
      microbial-associated molecules (pathogen-associated molecular patterns [PAMPs])
      and innate immune receptors (pathogen recognition receptors [PRRs]), such as NOD
      like receptors (NLRs) and Toll-like receptors (TLRs), control adaptive immune
      responses in inflammatory disorders. Polymorphisms of the genes encoding NOD2 and
      TLR4 are associated with a higher incidence of GVHD in HSC transplant recipients.
      Interestingly, NOD2 regulates GVHD through its inhibitory effect on antigen
      presenting cell (APC) function. These insights identify important mechanisms
      regarding the induction of GVHD through the interplay of microbial molecules and
      innate immunity, thus opening a new area for future therapeutic approaches. This
      review covers current knowledge of the role of PAMPs and PRRs in the control of
      adaptive immune responses during inflammatory diseases, particularly GVHD.

PMID- 20042728
TI  - Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem
      cell transplantation recipients.
AB  - Little is known about clinical and virologic manifestations of rhinovirus (HRV)
      and coronavirus (HCoV) infections after hematopoietic cell transplantation (HCT).
      We performed surveillance for 1 year and describe the natural history of these
      infections during the first 100 days after allogeneic HCT, when symptom surveys
      and upper respiratory samples were collected weekly. Samples were tested using RT
      PCR for HRVs and HCoVs (OC43, 229E, HKU1, and NL63). Among 215 patients, 64 (30%)
      patients had 67 infections. Day 100 cumulative incidence estimate was 22.3% for
      HRV and 11.1% for HCoV. Median duration of viral shedding was 3 weeks; prolonged
      shedding of at least 3 months occurred in 6 of 45 patients with HRV and 3 of 22
      with HCoV. Six patients with HRV and 9 with HCoV were asymptomatic. HRV infection
      was associated with rhinorrhea, congestion, postnasal drip, sputum, and cough;
      HCoV infection was not associated with respiratory symptoms or hepatic
      dysfunction. Lower respiratory infection developed in 2 patients with HRV before
      day 100, and 1 each with HRV and HCoV after day 100. HRV and HCoV infections are
      common in the first 100 days after HCT, viral shedding lasts more than 3 weeks in
      half, and lower respiratory infection is rare.

PMID- 20042729
TI  - Accelerated Ca2+ entry by membrane hyperpolarization due to Ca2+-activated K+
      channel activation in response to histamine in chondrocytes.
AB  - In articular cartilage inflammation, histamine release from mast cells is a key
      event. It can enhance cytokine production and matrix synthesis and also promote
      cell proliferation by stimulating chondrocytes. In this study, the functional
      impact of Ca(2+)-activated K(+) (K(Ca)) channels in the regulation of
      intracellular Ca(2+) concentration ([Ca(2+)](i)) in chondrocytes in response to
      histamine was examined using OUMS-27 cells, as a model of chondrocytes derived
      from human chondrosarcoma. Application of histamine induced a significant
      [Ca(2+)](i) rise and also membrane hyperpolarization, and both effects were
      mediated by the stimulation of H(1) receptors. The histamine-induced membrane
      hyperpolarization was attenuated to approximately 50% by large-conductance K(Ca)
      (BK) channel blockers, and further reduced by intermediate (IK) and small
      conductance K(Ca) (SK) channel blockers. The tonic component of histamine-induced
      [Ca(2+)](i) rise strongly depended on the presence of extracellular Ca(2+)
      ([Ca(2+)](o)) and was markedly reduced by La(3+) or Gd(3+) but not by nifedipine.
      It was significantly attenuated by BK channel blockers, and further blocked by
      the cocktail of BK, IK, and SK channel blockers. The K(Ca) blocker cocktail also
      significantly reduced the store-operated Ca(2+) entry (SOCE), which was induced
      by Ca(2+) addition after store-depletion by thapsigargin in [Ca(2+)](o) free
      solution. Our results demonstrate that the histamine-induced membrane
      hyperpolarization in chondrocytes due to K(Ca) channel activation contributes to
      sustained Ca(2+) entry mainly through SOCE channels in OUMS-27 cells. Thus, K(Ca)
      channels appear to play an important role in the positive feedback mechanism of
      [Ca(2+)](i) regulation in chondrocytes in the presence of articular cartilage
      inflammation.

PMID- 20042730
TI  - Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice.
AB  - Rett syndrome caused by mutations in methyl-CpG-binding protein 2 (Mecp2) gene
      shows abnormalities in autonomic functions in which brain stem norepinephrinergic
      systems play an important role. Here we present systematic comparisons of
      intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2(-/Y)
      and wild-type (WT) mice. Whole cell current clamp was performed in brain slices
      of 3- to 4-wk-old mice. Mecp2(-/Y) neurons showed stronger inward rectification
      and had shorter time constant than WT cells. The former was likely due to
      overexpression of inward rectifier K(+) (K(ir))4.1 channel, and the latter was
      attributable to the smaller cell surface area. The action potential duration was
      prolonged in Mecp2(-/Y) cells with an extended rise time. This was associated
      with a significant reduction in the voltage-activated Na(+) current density.
      After action potentials, >60% Mecp2(-/Y) neurons displayed fast and medium
      afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only
      mAHP. The mAHP amplitude was smaller in Mecp2(-/Y) neurons. The firing frequency
      was higher in neurons with mAHP, and the frequency variation was greater in cells
      with both fAHP and mAHP in Mecp2(-/Y) mice. Small but significant differences in
      spike frequency adaptation and delayed excitation were found in Mecp2(-/Y)
      neurons. These results indicate that there are several electrophysiological
      abnormalities in LC neurons of Mecp2(-/Y) mice, which may contribute to the
      dysfunction of the norepinephrine system in Rett syndrome.

PMID- 20042732
TI  - Shear stress-induced ATP-mediated endothelial constitutive nitric oxide synthase
      expression in human lymphatic endothelial cells.
AB  - To clarify the roles of lymphatic endothelial cells (LEC) in the regulation of
      endothelial constitutive nitric oxide synthase (ecNOS) expression, we examined
      the effects of shear stress on ecNOS immunohistochemical staining and mRNA and
      protein expression in human LEC as well as on ATP release from these cells. Shear
      stress at 0.5 or 1.0 dyn/cm(2) increased ecNOS immunohistochemical staining and
      ecNOS mRNA and protein expression in cultured LEC. The same strength of shear
      stress produced a significant release of ATP from the LEC. Exogenous ATP ranging
      in concentration from 10(-9) to 10(-6) M produced a significant increase in ecNOS
      immunohistochemical expression in a dose-dependent manner. The increase in ecNOS
      expression mediated by 10(-6)M ATP was significantly reduced by 10(-5) M suramin.
      Suramin (10(-5) M) caused a significant reduction in the shear stress-mediated
      increases in ecNOS immunohistochemical staining and mRNA expression. The shear
      stress-mediated increases in ecNOS expression were significantly reduced by 3 mM
      tetraethylammonium, 10(-4) M apamin, 10(-9) M iberiotoxin, 10(-5) M 2
      aminoethoxydephenyl borate, or 10(-5)M xestospongin C, but not 10(-5) M
      glybenclamide or 10(-5) M nifedipine. The shear stress-mediated increases in
      ecNOS expression were significantly potentiated by pinacidil or NS1619 in a dose
      dependent manner. The immunohistochemical expression of small- (SK(Ca)) and big
      conductance (BK(Ca)) Ca(2+)-activated K(+) channels was confirmed on the surfaces
      of human LEC. These findings suggest that shear stress produces a significant
      release of ATP from LEC, which activates the purinergic P2X/2Y receptor, thereby
      facilitating ecNOS mRNA and protein expression through inositol 1,4,5
      trisphosphate-mediated release of intracellular Ca(2+) ions and the activation of
      Ca(2+)-activated K(+) channels in LEC.

PMID- 20042731
TI  - Acetylsalicylic acid enhances purinergic receptor-mediated outward currents in
      rat megakaryocytes.
AB  - Purinergic receptor activation increases cytosolic Ca(2+) concentration in a
      fluctuating fashion, triggering oscillatory outward Ca(2+)-activated K(+)
      currents in rat megakaryocytes (MKs). Whole cell and nystatin-perforated patch
      clamp techniques were used to analyze changes in ionic conductance in MK with
      acetylsalicylic acid (ASA), a cyclooxygenase-1 inhibitor and antithrombotic
      agent. MKs are a model for platelet reactivity, particularly in ASA treatment
      failure (ASA resistance). Freshly isolated MKs were incubated 30 min in the
      absence or presence of 1 mM ASA. Using a K(+)-rich internal solution, we recorded
      outward currents in response to 10 microM ATP, 10 microM ADP, and 5 microM 2
      methyl-thio-ADP (2MeSADP) in the voltage-clamp mode. Agonist-induced currents
      decreased in amplitude over time, but this decline was attenuated by ASA in both
      continuous and repeated agonist challenge, indicating increased MK reactivity
      with ASA treatment. In separate experiments, heterologous desensitization was
      observed when MKs were stimulated with ADP after exposure to a thromboxane
      receptor agonist (U46619), indicating cross talk between thromboxane and
      purinergic pathways. Different cells, treated with ASA or MRS2179 (P2Y1 receptor
      antagonist), were stimulated with 2MeSADP. The dose-response curve was shifted to
      the left in both cases, suggesting increased MK reactivity. ASA also caused an
      increased interval between currents (delay). ASA attenuated desensitization of
      purinergic receptors and increased delay, again suggesting cross talk between
      purinergic and thromboxane pathways. These findings may be relevant to ASA
      resistance, because individual variations in sensitivity to the multiple effects
      of ASA on signaling pathways could result in insensitivity to its antiplatelet
      effects in some patients.

PMID- 20042733
TI  - Sphingosine 1-phosphate signaling is involved in skeletal muscle regeneration.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive lipid known to control cell growth
      that was recently shown to act as a trophic factor for skeletal muscle, reducing
      the progress of denervation atrophy. The aim of this work was to investigate
      whether S1P is involved in skeletal muscle fiber recovery (regeneration) after
      myotoxic injury induced by bupivacaine. The postnatal ability of skeletal muscle
      to grow and regenerate is dependent on resident stem cells called satellite
      cells. Immunofluorescence analysis demonstrated that S1P-specific receptors
      S1P(1) and S1P(3) are expressed by quiescent satellite cells. Soleus muscles
      undergoing regeneration following injury induced by intramuscular injection of
      bupivacaine exhibited enhanced expression of S1P(1) receptor, while S1P(3)
      expression progressively decreased to adult levels. S1P(2) receptor was absent in
      quiescent cells but was transiently expressed in the early regenerating phases
      only. Administration of S1P (50 microM) at the moment of myotoxic injury caused a
      significant increase of the mean cross-sectional area of regenerating fibers in
      both rat and mouse. In separate experiments designed to test the trophic effects
      of S1P, neutralization of endogenous circulating S1P by intraperitoneal
      administration of anti-S1P antibody attenuated fiber growth. Use of selective
      modulators of S1P receptors indicated that S1P(1) receptor negatively and S1P(3)
      receptor positively modulate the early phases of regeneration, whereas S1P(2)
      receptor appears to be less important. The present results show that S1P
      signaling participates in the regenerative processes of skeletal muscle.

PMID- 20042734
TI  - Thioredoxin 1 downregulates MCP-1 secretion and expression in human endothelial
      cells by suppressing nuclear translocation of activator protein 1 and redox
      factor-1.
AB  - To know whether thioredoxin 1 (Trx1) works for an antioxidant defense mechanism
      in atherosclerosis, the effect of Trx1 on the release of monocyte chemoattractant
      protein-1 (MCP-1), a potent chemoattractant for recruitment and accumulation of
      monocytes/macrophages in the intima of artery vessel, was investigated in human
      endothelial-like EA.hy 926 cells. It was found that overexpression of Trx1
      suppressed, whereas knockdown of endogenous Trx1 enhanced, oxidized low-density
      lipoprotein (oxLDL)-stimulated MCP-1 release and expression in the cells. It was
      also observed that overexpression of Trx1 suppressed, whereas depletion of
      endogenous Trx1 greatly promoted, nuclear translocation of c-Jun and the redox
      factor-1 (Ref-1). Electrophoretic mobility shift assay showed significantly
      reduced DNA-binding activity of activator protein-1 (AP-1) in Trx1-overexpressing
      cells but apparently enhanced DNA binding activity of AP-1 in Trx1-knockdown
      cells, indicating that nuclear Ref-1 rather than Trx1 itself finally dominates
      the regulation of AP-1 activity, although Trx1 is considered to upregulate AP-1
      activity. It was also observed that Trx1 depressed intracellular generation of
      reactive oxygen species (ROS). Diphenyleneiodonium (DPI), the inhibitor of NADPH
      oxidase, suppressed MCP-1 secretion, whereas transient expression of Nox1
      enhanced transcription of MCP-1 in endothelial cells. Assays with AP-1 and MCP-1
      luciferase reporters further demonstrated that transient expression of Trx1
      significantly depressed the transcriptional activity of c-Jun/c-Fos and
      consequent MCP-1 transcription. This study suggests that Trx1 inherently
      suppresses MCP-1 expression in vascular endothelium and may prevent
      atherosclerosis by depressing MCP-1 release. Besides the suppression of
      intracellular ROS generation, the inhibition of nuclear translocation of AP-1 and
      Ref-1 are mainly responsible for the downregulation of MCP-1 by Trx1.

PMID- 20042735
TI  - Association of ALDH2 genotypes with periodontitis progression.
AB  - The progression of periodontitis may be affected by ALDH2 genotypes with respect
      to the oxidation of acetaldehyde to acetate, which leads to the accumulation of
      acetaldehyde in plasma and potential toxic effects. We examined the prospective
      association of ALDH2 genotypes in terms of alcohol sensitivity between alcohol
      consumption and periodontal disease progression. In 2003, 224 of 256 (87.5%)
      individuals examined at baseline (1999) completed probing pocket depth
      measurements for the evaluation of periodontitis progression. Missing data on
      self-reported questionnaires and blood samples were excluded; therefore, 183
      samples were analyzed. Individuals who consumed > or = 33.0 g/day of alcohol
      exhibited high periodontal disease progression risk (OR = 3.54). ALDH2 *1/*2
      individuals who consumed > or = 33 g/day of alcohol displayed a significant odds
      ratio (OR = 4.28) of periodontitis progression risk, in contrast to ALDH2 *1/*1
      individuals. These results suggested that alcohol consumption as well as alcohol
      sensitivity may be a risk factor for periodontitis progression.

PMID- 20042736
TI  - Effect of gamma irradiation on ultimate tensile strength of enamel and dentin.
AB  - The effect of gamma irradiation therapy on the ultimate tensile strength (UTS) of
      enamel and dentin in relation to prism orientation, dentin tubule orientation,
      and location is unknown. It was hypothesized that tubule and prism orientation,
      location, and irradiation have an effect on the UTS of dental structures. Forty
      human third molars were used, half of which were subjected to 60 Gy of gamma
      irradiation, in daily increments of 2 Gy. The specimens were evaluated by
      microtensile testing. Results showed that irradiation treatment significantly
      decreased the UTS of coronal and radicular dentin and of enamel, regardless of
      tubule or prism orientation. With or without irradiation, enamel was
      significantly stronger when tested parallel to its prismatic orientation. Coronal
      and radicular dentin of non-irradiated specimens presented significantly higher
      UTS when tested perpendicularly to tubule orientation. However, when the teeth
      were irradiated, the influence of tubule orientation disappeared, demonstrating
      that irradiation is more harmful to organic components.

PMID- 20042737
TI  - Autosomal-dominant ankyloglossia and tooth number anomalies.
AB  - Ankyloglossia is a congenital oral anomaly characterized by the presence of a
      hypertrophic lingual frenulum. It frequently accompanies X-linked cleft palate
      and is sometimes seen alone due to mutations in the gene encoding the
      transcription factor TBX22, while knockout of Lgr5 in the mouse results in
      ankyloglossia. The aim of the present study was to characterize the phenotype and
      to verify sequence variations in the LGR5 gene in a Brazilian family with
      ankyloglossia associated with tooth number anomalies. Twelve individuals of three
      generations were submitted to physical, oral, and radiographic examinations and
      molecular analysis. Eight had ankyloglossia with various degrees of severity. Six
      also had hypodontia in the lower incisor region; one had a supernumerary tooth in
      this region, and another had a supernumerary tooth in the lower premolar region.
      The characterization of this family determined an autosomal-dominant inheritance
      and excluded the LGR5 gene mutations as being involved in the pathogenesis of
      this condition.

PMID- 20042738
TI  - New insights into hyperglycemia-induced molecular changes in microvascular cells.
AB  - Hyperglycemia is the most prevalent characteristic of diabetes and plays a
      central role in mediating adverse effects on vascular cells during the
      progression of diabetic vascular complications. In diabetic microangiopathy,
      hyperglycemia induces biochemical and molecular changes in microvascular cells
      that ultimately progress to retinal, renal, and neural complications and extends
      to other complications, including advanced periodontal disease. In this review,
      we describe changes involving basement membrane thickening, tissue remodeling,
      gap junctions, inflammation, cytokines, and transcription factors, and their
      effects on the pathogenesis of diabetic microvascular complications. The majority
      of the changes described relate to retinal microangiopathy, since
      ultrastructural, structural, and biochemical alterations have been well
      characterized in this tissue.

PMID- 20042739
TI  - Hyper-responsive phenotype in localized aggressive periodontitis.
AB  - The 'hyper-responsive' trait is an increased inflammatory response upon
      stimulation of innate immune receptors. Our objective was to determine if a hyper
      reactive trait is present in a cohort diagnosed with aggressive periodontitis
      (LAgP). Peripheral blood was collected from 30 LAgP, 10 healthy unrelated, and 10
      healthy sibling participants and stimulated with lipopolysaccharide (LPS) from E.
      coli and P. gingivalis. Cyto/chemokine response profiles were evaluated and
      analyzed by ANOVA. Elevated levels of pro-inflammatory cyto/chemokines were
      detected in E. coli and P. gingivalis LPS-stimulated LAgP cultures when compared
      with those of healthy unrelated control individuals. Periodontally healthy
      siblings presented with attenuated hyper-inflammatory cyto/chemokine profiles.
      Regression analysis demonstrated the hyper-reactive trait to be concomitant
      expression of pro-inflammatory cyto/chemokines and an absence of anti
      inflammatory mediator expression. Our findings demonstrate hyper-responsive trait
      in a LAgP cohort, along with an attenuated hyper-responsiveness in healthy
      siblings, which can be induced in response to multiple TLR ligations.

PMID- 20042740
TI  - Formation of the tooth-bone interface.
AB  - Not only are teeth essential for mastication, but also missing teeth are
      considered a social handicap due to speech and aesthetic problems, with a
      resulting high impact on emotional well-being. Several treatment procedures are
      currently available for tooth replacement with mostly inert prosthetic materials
      and implants. Natural tooth substitution based on copying the developmental
      process of tooth formation is particularly challenging and creates a rapidly
      developing area of molecular dentistry. In any approach, functional interactions
      among the tooth, the surrounding bone, and the periodontium must be established.
      Therefore, recent research in craniofacial genetics searches for mechanisms
      responsible for correct cell and tissue interactions, not only within a specific
      structure, but also in the context of supporting structures. A tooth crown that
      is not functionally anchored to roots and bone is useless. This review aims to
      summarize the developmental and tissue homeostatic aspects of the tooth-bone
      interface, from the initial patterning toward tooth eruption and lifelong
      interactions between the tooth and its surrounding alveolar bone.

PMID- 20042741
TI  - Finite element analysis of a TMJ implant.
AB  - To determine the causes of failure of an artificial temporomandibular joint
      implant, one must study the magnitude and location of the maximum stresses under
      physiological loading. In this study, we analyzed the stresses in a commercially
      available TMJ implant, the bone (i.e., mandible), and the bone-implant interface
      using a finite element software package. Both titanium and Co-Cr-Mo/Vitallium
      metals as well as bones with various degrees of osteoporosis were studied. The
      results of the analysis showed that the maximum stresses occurred at the location
      of the first screw hole (closest to the condyle) of the implant. In addition, the
      highest microstrains were observed in the bone adjacent to the first screw hole.
      The results of our study have potential clinical benefit in terms of improved
      implant design and hence better performance.

PMID- 20042742
TI  - Specific Lactobacillus/Mutans Streptococcus co-aggregation.
AB  - Selective interaction of mutans streptococci with benign bacteria could present
      an opportunity for their removal from the mouth without disruption of other oral
      flora. This study was conducted to find probiotic lactobacilli that could
      specifically co-aggregate in vitro with mutans streptococci, but not with other
      plaque commensals. A search of 624 lactobacilli among a large culture library
      revealed 6 strains, all classifiable as L. paracasei or L. rhamnosus, which met
      this criterion. Such novel, specific co-aggregation, however, was not a general
      characteristic of these species or the genus Lactobacillus. The co-aggregation by
      these specific lactobacilli was characterized as heat treatment (autoclaving)-
      and protease-resistant, lectin-independent, not inactivated by sugar substitutes,
      operational over a wide pH range, unaffected by whole saliva, but calcium
      dependent. It is thus seen to present a potential strategy for in vivo alteration
      of plaque biofilm and caries.

PMID- 20042743
TI  - Alteration of PTGS2 promoter methylation in chronic periodontitis.
AB  - Levels of prostaglandin E(2) and the prostaglandin-endoperoxide synthase-2
      (PTGS2, or COX-2) increase in actively progressing periodontal lesions, but
      decrease in chronic disease. We hypothesized that chronic inflammation is
      associated with altered DNA methylation levels within the PTGS2 promoter, with
      effects on COX-2 mRNA expression. PTGS2 promoter methylation levels from
      periodontally inflamed gingival biopsies showed a 5.06-fold increase as compared
      with non-inflamed samples (p = 0.03), and the odds of methylation in a CpG site
      in the inflamed gingival group is 4.46 times higher than in the same site in the
      non-inflamed group (p = 0.016). The level of methylation at -458 bp was inversely
      associated with transcriptional levels of PTGS2 (RT-PCR) (p = 0.01). Analysis of
      the data suggests that, in chronically inflamed tissues, there is a
      hypermethylation pattern of the PTGS2 promoter in association with a lower level
      of PTGS2 transcription, consistent with a dampening of COX-2 expression in
      chronic periodontitis. These findings suggest that the chronic persistence of the
      biofilm and inflammation may be associated with epigenetic changes in local
      tissues at the biofilm-gingival interface.

PMID- 20042744
TI  - The amelogenin C-terminus is required for enamel development.
AB  - The abundant amelogenin proteins are responsible for generating proper enamel
      thickness and structure, and most amelogenins include a conserved hydrophilic C
      terminus. To evaluate the importance of the C-terminus, we generated transgenic
      mice that express an amelogenin lacking the C-terminal 13 amino acids (CTRNC).
      MicroCT analysis of TgCTRNC29 teeth (low transgene number) indicated that molar
      enamel density was similar to that of wild-type mice, but TgCTRNC18 molar enamel
      (high transgene number) was deficient, indicating that extra transgene copies
      were associated with a more severe phenotype. When amelogenin-null (KO) and
      TgCTRNC transgenic mice were mated, density and volume of molar enamel from
      TgCTRNCKO offspring were not different from those of KO mice, indicating that
      neither TgCTRNC18 nor TgCTRNC29 rescued enamel's physical characteristics.
      Because transgenic full-length amelogenin partially rescues both density and
      volume of KO molar enamel, it was concluded that the amelogenin C-terminus is
      essential for proper enamel density, volume, and organization.

PMID- 20042745
TI  - Launching HITECH.

PMID- 20042746
TI  - Responses to 2009 H1N1 vaccine in children 3 to 17 years of age.

PMID- 20042747
TI  - Carrots, sticks, and health care reform--problems with wellness incentives.

PMID- 20042748
TI  - "Play-or-pay" insurance reforms for employers--confusion and inequity.

PMID- 20042749
TI  - Implementation and enforcement of health care reform--federal versus state
      government.

PMID- 20042750
TI  - Phytohabitans suffuscus gen. nov., sp. nov., an actinomycete of the family
      Micromonosporaceae isolated from plant roots.
AB  - An actinomycete strain, K07-0523(T), was isolated from the roots of an orchid
      collected in Okinawa prefecture, Japan. 16S rRNA gene sequence analysis indicated
      that the new strain belonged to the family Micromonosporaceae and the similarity
      values between strain K07-0523(T) and the type species of 24 genera in the family
      Micromonosporaceae were 93.3-97.7 %. Strain K07-0523(T) contained D-glutamic
      acid, glycine, D-alanine, meso-diaminopimelic acid, hydroxydiaminopimelic acid
      and L-lysine in the cell wall. The major menaquinones were MK-9(H(6)), MK
      10(H(4)) and MK-10(H(6)). Galactose, glucose, mannose, ribose and xylose were
      present in the whole-cell sugars. The acyl type of the peptidoglycan was
      glycolyl. Major fatty acids were anteiso-C(17 : 0), iso-C(17 : 0), iso-C(16 : 0)
      and iso-C(15 : 0). Phosphatidylethanolamine was detected as the major
      phospholipid and corresponded to phospholipid type II. The G+C content of the
      genomic DNA was 73 mol%. On the basis of phylogenetic and chemotaxonomic data,
      the new strain represents a member of a new genus and novel species, namely
      Phytohabitans suffuscus gen. nov., sp. nov., in the family Micromonosporaceae.
      The type strain of the type species is K07-0523(T) (=DSM 45306(T)=NBRC
      105367(T)).

PMID- 20042751
TI  - Actinomadura scrupuli sp. nov., isolated from rock.
AB  - A novel actinomycete, designated strain R-Ac121(T), was isolated from a small
      stone collected from an agricultural field in Jeju, Republic of Korea. The
      organism formed abundant vegetative mycelium that was branched and twisted. The
      reverse colour of colonies was brownish-yellow. Non-motile, wrinkled arthrospores
      were produced directly on the substrate mycelium. Aerial mycelium and sporangia
      were not observed. A neighbour-joining tree based on 16S rRNA gene sequences
      indicated that the isolate formed a distinct clade within the radiation of the
      family Thermomonosporaceae. The highest 16S rRNA gene sequence identity was found
      with the type strain of Spirillospora rubra (97.3 % sequence similarity) followed
      by those of Actinoallomurus purpureus (97.0 %), Actinomadura alba (96.5 %),
      Actinomadura fibrosa (96.5 %) and Actinomadura echinospora (96.4 %). The cell
      wall contained meso-diaminopimelic acid. The whole-cell sugars were rhamnose,
      glucose, ribose, xylose and arabinose. The polar lipids included
      diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol. The major
      menaquinone was MK-9(H(6)) and the predominant fatty acids were iso-C(16 : 0),
      C(16 : 0), C(17 : 1)omega8c and 10-methyl C(17 : 0). The DNA G+C content was 71.8
      mol%. The combination of morphological, chemotaxonomic and phylogenetic data
      clearly supports the separation of the organism from recognized species of the
      genus Actinomadura and related genera. On the basis of the data presented here,
      strain R-Ac121(T) represents a novel species of the genus Actinomadura, for which
      the name Actinomadura scrupuli sp. nov. is proposed. The type strain is strain R
      Ac121(T) (=KCTC 19488(T) =DSM 45225(T)).

PMID- 20042752
TI  - Images in clinical medicine. Radiation pneumonitis after radiotherapy for breast
      cancer.

PMID- 20042753
TI  - Household transmission of 2009 pandemic influenza A (H1N1) virus in the United
      States.
AB  - BACKGROUND: As of June 11, 2009, a total of 17,855 probable or confirmed cases of
      2009 pandemic influenza A (H1N1) had been reported in the United States. Risk
      factors for transmission remain largely uncharacterized. We characterize the risk
      factors and describe the transmission of the virus within households. METHODS:
      Probable and confirmed cases of infection with the 2009 H1N1 virus in the United
      States were reported to the Centers for Disease Control and Prevention with the
      use of a standardized case form. We investigated transmission of infection in 216
      households--including 216 index patients and their 600 household contacts--in
      which the index patient was the first case patient and complete information on
      symptoms and age was available for all household members. RESULTS: An acute
      respiratory illness developed in 78 of 600 household contacts (13%). In 156
      households (72% of the 216 households), an acute respiratory illness developed in
      none of the household contacts; in 46 households (21%), illness developed in one
      contact; and in 14 households (6%), illness developed in more than one contact.
      The proportion of household contacts in whom acute respiratory illness developed
      decreased with the size of the household, from 28% in two-member households to 9%
      in six-member households. Household contacts 18 years of age or younger were
      twice as susceptible as those 19 to 50 years of age (relative susceptibility,
      1.96; Bayesian 95% credible interval, 1.05 to 3.78; P=0.005), and household
      contacts older than 50 years of age were less susceptible than those who were 19
      to 50 years of age (relative susceptibility, 0.17; 95% credible interval, 0.02 to
      0.92; P=0.03). Infectivity did not vary with age. The mean time between the onset
      of symptoms in a case patient and the onset of symptoms in the household contacts
      infected by that patient was 2.6 days (95% credible interval, 2.2 to 3.5).
      CONCLUSIONS: The transmissibility of the 2009 H1N1 influenza virus in households
      is lower than that seen in past pandemics. Most transmissions occur soon before
      or after the onset of symptoms in a case patient.

PMID- 20042755
TI  - Public reporting of discharge planning and rates of readmissions.
AB  - BACKGROUND: A reduction in hospital readmissions may improve quality and reduce
      costs. The Centers for Medicare and Medicaid Services has initiated a national
      effort to measure and publicly report on the conduct of discharge planning. We
      know little about how U.S. hospitals perform on the current discharge metrics,
      the factors that underlie better performance, and whether better performance is
      related to lower readmission rates. METHODS: We examined hospital performance on
      the basis of two measures of discharge planning: the adequacy of documentation in
      the chart that discharge instructions were provided to patients with congestive
      heart failure, and patient-reported experiences with discharge planning. We
      examined the association between performance on these measures and rates of
      readmission for congestive heart failure and pneumonia. RESULTS: We found a weak
      correlation in performance between the two discharge measures (r=0.05, P<0.001).
      Although larger hospitals performed better on the chart-based measure, smaller
      hospitals and those with higher nurse-staffing levels performed better on the
      patient-reported measure. We found no association between performance on the
      chart-based measure and readmission rates among patients with congestive heart
      failure (readmission rates among hospitals performing in the highest quartile vs.
      the lowest quartile, 23.7% vs. 23.5%; P=0.54) and only a very modest association
      between performance on the patient-reported measure and readmission rates for
      congestive heart failure (readmission rates among hospitals performing in the
      highest quartile vs. the lowest quartile, 22.4% vs. 24.7%; P<0.001) and pneumonia
      (17.5% vs. 19.5%, P<0.001). CONCLUSIONS: Our findings suggest that current
      efforts to collect and publicly report data on discharge planning are unlikely to
      yield large reductions in unnecessary readmissions.

PMID- 20042756
TI  - Activated protein C for sepsis.

PMID- 20042754
TI  - Outbreak of 2009 pandemic influenza A (H1N1) at a New York City school.
AB  - BACKGROUND: In April 2009, an outbreak of novel swine-origin influenza A (2009
      H1N1 influenza) occurred at a high school in Queens, New York. We describe the
      outbreak and characterize the clinical and epidemiologic aspects of this novel
      virus. METHODS: The New York City Department of Health and Mental Hygiene
      characterized the outbreak through laboratory confirmation of the presence of the
      2009 H1N1 virus in nasopharyngeal and oropharyngeal specimens and through
      information obtained from an online survey. Detailed information on exposure and
      the onset of symptoms was used to estimate the incubation period, generation
      time, and within-school reproductive number associated with 2009 H1N1 influenza,
      with the use of established techniques. RESULTS: From April 24 through May 8,
      infection with the 2009 H1N1 virus was confirmed in 124 high-school students and
      employees. In responses to the online questionnaire, more than 800 students and
      employees (35% of student respondents and 10% of employee respondents) reported
      having an influenza-like illness during this period. No persons with confirmed
      2009 H1N1 influenza or with influenza-like illness had severe symptoms. A linkage
      with travel to Mexico was identified. The estimated median incubation period for
      confirmed 2009 H1N1 influenza was 1.4 days (95% confidence interval [CI], 1.0 to
      1.8), with symptoms developing in 95% of cases by 2.2 days (95% CI, 1.7 to 2.6).
      The estimated median generation time was 2.7 days (95% CI, 2.0 to 3.5). We
      estimate that the within-school reproductive number was 3.3. CONCLUSIONS: The
      findings from this investigation suggest that 2009 H1N1 influenza in the high
      school was widespread but did not cause severe illness. The reasons for the rapid
      and extensive spread of influenza-like illnesses are unknown. The natural history
      and transmission of the 2009 H1N1 influenza virus appear to be similar to those
      of previously observed circulating pandemic and interpandemic influenza viruses.

PMID- 20042757
TI  - Images in clinical medicine. Vanishing mediastinal mass.

PMID- 20042758
TI  - Case records of the Massachusetts General Hospital. Case 41-2009. A 16-year-old
      boy with hypothermia and frostbite.

PMID- 20042759
TI  - Aging--lost in translation?

PMID- 20042760
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20042761
TI  - Sex hormone-binding globulin and risk of type 2 diabetes.

PMID- 20042762
TI  - Maternal and neonatal herpes simplex virus infections.

PMID- 20042763
TI  - Human GM-CSF autoantibodies and reproduction of pulmonary alveolar proteinosis.

PMID- 20042764
TI  - Board oversight of patient care quality in community health systems.
AB  - In hospitals and health systems, ensuring that standards for the quality of
      patient care are established and continuous improvement processes are in place
      are among the board's most fundamental responsibilities. A recent survey has
      examined governance oversight of patient care quality at 123 nonprofit community
      health systems and compared their practices with current benchmarks of good
      governance. The findings show that 88% of the boards have established standing
      committees on patient quality and safety, nearly all chief executive officers'
      performance expectations now include targets related to patient quality and
      safety, and 96% of the boards regularly receive formal written reports regarding
      their organizations' performance in relation to quality measures and standards.
      However, there continue to be gaps between present reality and current benchmarks
      of good governance in several areas. These gaps are somewhat greater for
      independent systems than for those affiliated with a larger parent organization.

PMID- 20042765
TI  - Common formats allow uniform collection and reporting of patient safety data by
      patient safety organizations.

PMID- 20042767
TI  - Effect of right ventricular versus biventricular pacing on electrical remodeling
      in the normal heart.
AB  - BACKGROUND: Biventricular (BIV) pacing can improve cardiac function in heart
      failure by altering the mechanical and electric substrates. We investigated the
      effect of BIV versus right ventricular (RV) pacing on the normal heart. METHODS
      AND RESULTS: Male New Zealand White rabbits (n=33) were divided into 3 groups:
      sham-operated (control), RV pacing, and BIV pacing groups. Four weeks after
      surgery, the native QT (P=0.004) interval was significantly shorter in the BIV
      group compared with the RV or sham-operated groups. Also, compared with rabbits
      in the RV group, rabbits in the BIV group had shorter RV effective refractory
      period at all cycle lengths and shorter LV paced QT interval during the drive
      train of stimuli and close to refractoriness (P<0.001 for all comparisons).
      Protein expression of the KVLQT1 was significantly increased in the BIV group
      compared with the RV and control groups, whereas protein expression of SCN5A and
      connexin43 was significantly decreased in the RV compared with the other study
      groups. Erg protein expression was significantly increased in both pacing groups
      compared with the controls. CONCLUSIONS: In this rabbit model, we demonstrate a
      direct effect of BIV but not RV pacing on shortening the native QT interval as
      well as the paced QT interval during burst pacing and close to the ventricular
      effective refractory period. These findings underscore the fact that the effect
      of BIV pacing is partially mediated through direct electric remodeling and may
      have implications as to the effect of BIV pacing on arrhythmia incidence and
      burden.

PMID- 20042768
TI  - Chest compressions cause recurrence of ventricular fibrillation after the first
      successful conversion by defibrillation in out-of-hospital cardiac arrest.
AB  - BACKGROUND: Unlike Resuscitation Guidelines (GL) 2000, GL2005 advise resuming
      cardiopulmonary resuscitation (CPR) immediately after defibrillation. We
      hypothesized that immediate CPR resumption promotes earlier recurrence of
      ventricular fibrillation (VF). METHODS AND RESULTS: This study used data of a
      prospective per-patient randomized controlled trial. Automated external
      defibrillators used by first responders were randomized to either (1) perform
      postshock analysis and prompt rescuers to a pulse check (GL2000), or (2) resume
      CPR immediately after defibrillation (GL2005). Continuous recordings of ECG and
      impedance signals were collected from all patients with an out-of-hospital
      cardiac arrest to whom a randomized automated external defibrillator was applied.
      We included patients with VF as their initial rhythm in whom CPR onset could be
      determined from the ECG and impedance signals. Time intervals are presented as
      median (Q1-to-Q3). Of 361 patients, 136 met the inclusion criteria: 68 were
      randomly assigned to GL2000 and 68 to GL2005. Rescuers resumed CPR 30 (21-to-39)
      and 8 (7-to-9) seconds, respectively, after the first shock that successfully
      terminated VF (P<0.001); VF recurred after 40 (21-to-76) and 21 (10-to-80)
      seconds, respectively (P=0.001). The time interval between start of CPR and VF
      recurrence was 6 (0-to-67) and 8 (3-to-61) seconds, respectively (P=0.88). The
      hazard ratio for VF recurrence in the first 2 seconds of CPR was 15.5 (95%
      confidence interval, 5.63 to 57.7) compared with before CPR resumption. After
      more than 8 seconds of CPR, the hazard of VF recurrence was similar to before CPR
      resumption. CONCLUSIONS: Early CPR resumption after defibrillation causes early
      VF recurrence. Clinical Trial Registration- clinicaltrials.gov Identifier:
      ISRCTN72257677.

PMID- 20042769
TI  - Omega-3 fatty acid supplementation does not reduce risk of atrial fibrillation
      after coronary artery bypass surgery: a randomized, double-blind, placebo
      controlled clinical trial.
AB  - BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to
      reduce the risk of sudden cardiac death presumed to be due to fatal ventricular
      arrhythmias, but their effect on atrial arrhythmias is unclear. METHODS AND
      RESULTS: Patients (n=108) undergoing coronary artery bypass graft surgery were
      randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5
      days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3
      PUFA were measured in serum at study entry and at surgery and in right atrial
      appendage tissue at surgery. Echocardiography was used to assess left ventricular
      function and left atrial dimensions. Postoperative continuous ECG monitoring
      (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a
      daily 12-lead ECG and clinical review if patients remained in the hospital beyond
      5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation
      (AF) > or =30 seconds (primary outcome). Clinical AF, AF burden (% time in AF),
      hospital stay, and intensive care/high dependency care stay were measured as
      secondary outcomes. One hundred three patients completed the study (51 in the
      placebo group and 52 in the n-3 PUFA group). There were no clinically relevant
      differences in baseline characteristics between groups. n-3 PUFA levels were
      higher in serum and right atrial tissue in the active treatment group. There was
      no significant difference between groups in the primary outcome of AF (95%
      confidence interval [CI], -6% to 30%, P=0.28) in any of the secondary outcomes or
      in AF-free survival. CONCLUSIONS: Omega-3 PUFA do not reduce the risk of AF after
      coronary artery bypass graft surgery. Clinical Trial Registration-
      www.ukcrn.org.uk. Identifier: 4437.

PMID- 20042770
TI  - Diabetes Care. Introduction.

PMID- 20042773
TI  - Summary of revisions for the 2010 Clinical Practice Recommendations.

PMID- 20042774
TI  - Executive summary: Standards of medical care in diabetes--2010.

PMID- 20042772
TI  - Standards of medical care in diabetes--2010.

PMID- 20042775
TI  - Diagnosis and classification of diabetes mellitus.

PMID- 20042776
TI  - Diabetes care in the school and day care setting.

PMID- 20042777
TI  - Diabetes management in correctional institutions.

PMID- 20042778
TI  - Diabetes and employment.

PMID- 20042779
TI  - Third-party reimbursement for diabetes care, self-management education, and
      supplies.

PMID- 20042783
TI  - Publishing in the field of brain plasticity, repair and rehabilitation: The 20th
      Anniversary issue of Restorative Neurology and Neuroscience.
AB  - The journal Restorative Neurology and Neuroscience (RNN) now celebrates its 20th
      anniversary. Since 1989 RNN has published scientific findings in the emerging
      fields of brain plasticity, repair and rehabilitation via original scientific
      publications and review papers in basic research (animal experiments, in vitro
      studies) and clinical science. During the last decade RNN had a steady progress
      in reference value and scientific impact, reaching an ISI-impact factor of 1.978
      (2008) and has published a total of 717 papers. The journal's success can be
      explained by different factors: (1) neuroplasticity, regeneration, recovery and
      rehabilitation have developed to main stream subjects with a worldwide increase
      in the number of publications and their citation rate, (2) RNN has published
      numerous special issues which summarize the work of leading experts in
      specialized sub-fields, (3) a dedicated, highly qualified editorial board (4) the
      quality of papers submitted to RNN has increased over time. RNN has now become a
      visible and leading source of original scientific information in the space of
      brain plasticity, rehabilitation and repair.

PMID- 20042784
TI  - Anti-kindling achieved by stimulation targeting slow synaptic dynamics.
AB  - PURPOSE: Different stimulation techniques are introduced which specifically
      modulate the slow synaptic dynamics in a neuronal network model of the
      subthalamic nucleus with activity dependent synaptic plasticity. METHODS: A
      modeling approach is utilized to investigate the effects of the different
      stimulation techniques. In particular, the short-term and long-term outcome is
      studied in a mathematical model for a population of bursting STN neurons subject
      to synaptic plasticity with symmetric spike timing characteristics. In our
      mathematical model in the absence of stimulation synchronized network states with
      strong connectivity (modeling disease states) as well as desynchronized states
      with weak connectivity (modeling healthy states) are stable. RESULTS: We
      demonstrate that different stimulation techniques induce an anti-kindling by
      shifting the target population to a weakly connected, desynchronized state.
      Intriguingly, long-term anti-kindling can even be achieved although during
      stimulus delivery the neuronal synchrony hardly decreases or even slightly
      increases. The therapeutic index and the impact of inhibition, calculated to
      compare the different stimulation techniques, indicate that coordinated rest
      stimulation might be particularly robust and reliable. CONCLUSIONS: The presented
      stimulation strategies and the results of our modeling study might have strong
      implications in the context of deep brain stimulation.

PMID- 20042780
TI  - National standards for diabetes self-management education.

PMID- 20042785
TI  - Embryonic mescencephalon derived neurospheres contain progenitors as well as
      differentiated neurons and glia.
AB  - PURPOSE: Stem cells and progenitor cells in the central nervous system may have
      potential for therapeutic use in patients with degenerative diseases or after
      injury. Neural precursor cells can be grown in culture in the presence of
      mitogens as aggregates termed neurospheres (NSs), as a source of proliferating
      progenitor cells. Withdrawal of mitogen and allowing the NSs to adhere to a
      substrate is the conventional way to study the differentiation potential of the
      progenitor cells propagated in NSs form. Here we asked if differentiation occurs
      within NSs cultured in the normal manner, in the presence of mitogen. METHODS: We
      used non-passaged NSs derived from E13.5 mouse ventral mesencephalon. RESULTS:
      The NSs contained not only progenitor cells but also phenotypically
      differentiated neurons and glia, in the presence of mitogen. Extracellular matrix
      molecules (fibronectin, laminin and collagen type IV) were also detected within
      these NSs, which may aid in the differentiation of progenitors inside the NSs.
      The cell types within NSs were also organized in a way that the differentiated
      cells were found in the inner cell mass while progenitors were found in the outer
      region. Additionally, the proportion of differentiated cell types within the NSs
      was also affected by exposure to different mitogens. Moreover, when placed
      together in to co-culture, dissociated embryonic striatal and mesencephalic cells
      aggregated spontaneously to form mixed NSs, enhancing the eventual
      differentiation into dopaminergic neurons from progenitors within these NSs.
      CONCLUSION: Therefore, the NSs contained progenitor cells and differentiated
      neurons and glial cells. In addition, NS culture system can be used to study
      cellular differentiation in vitro in non-adherent conditions.

PMID- 20042786
TI  - Effect of whole-body vibration on quadriceps spasticity in individuals with
      spastic hypertonia due to spinal cord injury.
AB  - PURPOSE: Individuals with spinal cord injury (SCI) often have involuntary, reflex
      evoked muscle activity resulting in spasticity. Vibration may modulate reflex
      activity thereby decreasing spasticity. This study suggests feasibility of using
      whole-body vibration (WBV) to decrease quadriceps spasticity in individuals with
      SCI. METHODS: Participants were individuals (n=16) with spastic quadriceps
      hypertonia due to chronic SCI (> 1 year). Quadriceps spasticity was measured by
      gravity-provoked stretch (Pendulum Test) before (initial) and after (final) a 3
      day/week, 12-session WBV intervention. In addition, differences between immediate
      (immediate post-WBV) and delayed (delayed post-WBV) within-session effects were
      quantified. Finally, we assessed response differences between subjects who did
      and those who did not use antispastic agents. RESULTS: There was a significant
      reduction in quadriceps spasticity after participation in a WBV intervention that
      persisted for at least eight days. Within a WBV session, spasticity was reduced
      in the delayed post-WBV test compared to the immediate post-WBV test. The WBV
      intervention was associated with similar changes in quadriceps spasticity in
      subjects who did and those who did not use antispastic agents. CONCLUSIONS:
      Vibration may be a useful adjunct to training in those with spasticity. Future
      studies should directly compare the antispastic effects of vibration to those of
      antispastic agents.

PMID- 20042787
TI  - Effects of electrical stimulation and gonadal steroids on rat facial nerve
      regenerative properties.
AB  - PURPOSE: The neurotherapeutic effects of nerve electrical stimulation and gonadal
      steroids have independently been demonstrated. The purpose of this study was to
      investigate the therapeutic potential of a combinatorial treatment strategy of
      electrical stimulation and gonadal steroids on peripheral nerve regeneration.
      METHODS: Following a facial nerve crush axotomy in gonadectomized adult male
      rats, testosterone propionate (TP), dihydrotestosterone (DHT), or estradiol
      (E(2)) was systemically administered with/without daily electrical stimulation of
      the proximal nerve stump. Facial nerve outgrowth was assessed at 4 and 7 days
      post-axotomy using radioactive labeling. RESULTS: Administration of electrical
      stimulation alone reduced the estimated delay in sprout formation but failed to
      accelerate the overall regeneration rate. Conversely, TP treatment alone
      accelerated the regeneration rate by approximately 10% but had no effect on the
      sprouting delay. Combining TP with electrical stimulation, however, maintained
      the enhanced rate and reduced the sprouting delay. DHT treatment alone failed to
      alter the regeneration rate but combining it with electrical stimulation
      increased the rate by 10%. E(2) treatment alone increased the regeneration rate
      by approximately 5% but with electrical stimulation, there was no additional
      effect. CONCLUSIONS: Electrical stimulation and gonadal steroids differentially
      enhanced regenerative properties. TP, an aromatizable androgen, augmented
      regeneration most, suggesting a synergism between androgenic and estrogenic
      effects. Therapeutically, combining electrical stimulation with gonadal steroids
      may boost regenerative properties more than the use of either treatment alone.

PMID- 20042788
TI  - Non-invasive cortical stimulation improves post-stroke attention decline.
AB  - PURPOSE: Attention decline after stroke is common and hampers the rehabilitation
      process, and non-invasive transcranial direct current stimulation (tDCS) has the
      potential to elicit behavioral changes by modulating cortical excitability. The
      authors tested the hypothesis that a single session of non-invasive cortical
      stimulation with excitatory anodal tDCS applied to the left dorsolateral
      prefrontal cortex (DLPFC) can improve attention in stroke patients. METHODS: Ten
      patients with post-stroke cognitive decline (MMSE 25) and 10 age-matched healthy
      controls participated in this double blind, sham-controlled, crossover study
      involving the administration of real (2 mA for 20 min) or sham stimulation (2 mA
      for 1 min) to the left DLPFC. Attention was measured using a computerized Go/No
      Go test before and after intervention. Improvements in accuracy and speed after
      stimulation relative to baseline were compared for real and sham stimulations.
      RESULTS: In healthy controls, no significant improvement in Go/No-Go test was
      observed after either real or sham stimulation. However, in stroke patients, tDCS
      led to a significant improvement in response accuracy at 1 hour post-stimulation
      relative to baseline, and this improvement was maintained until 3 hours post
      stimulation (P< 0.05), whereas sham stimulation did not lead to a significant
      improvement in response accuracy (P> 0.05). Changes in reaction times were
      comparable for the two stimulations (P> 0.05). CONCLUSION: Non invasive anodal
      tDCS applied to the left DLPFC was found to improve attention versus sham
      stimulation in stroke patients, which suggests that non-invasive cortical
      intervention could potentially be used during rehabilitative training to improve
      attention.

PMID- 20042789
TI  - Local administration of DFO-loaded lipid particles improves recovery after end-to
      end reconstruction of rat median nerve.
AB  - PURPOSE: The improvement of regeneration and functional recovery after peripheral
      nerve injury is a major challenge in neurosurgery. Although microsurgical
      techniques for nerve reconstruction have seen great advancements over the last
      years, the clinical outcome with patients is often unsatisfactory. The aim of the
      present study was to investigate if administration of the iron chelator
      Deferroxamine (DFO), can improve postoperative outcome in the rat median nerve
      reconstruction model. METHODS: After complete transection, the right median nerve
      was repaired by end-to-end neurorrhaphy. The suture site was wrapped by a 1-cm
      long external jugular vein segment, either empty or filled with DFO-loaded lipid
      particles (Perineurin or with a vehicle (unloaded lipid particles) alone.
      Functional testing was carried out weekly by means of the grasping test. At the
      time of withdrawal, 12 weeks post-operatively, muscle tropism recovery was
      assessed by weighing flexor digitorum sublimis muscle that is innervated by the
      median nerve only. Before harvesting of the nerve specimens electrophysiological
      analyses were performed with measuring the latency, the threshold and the
      conduction velocity. Finally, the repaired nerves were withdrawn for
      immunocytochemistry with a neurofilament antibody and axon quantitative
      morphology. RESULTS: The comparison between the groups showed that intraoperative
      application of the DFO-loaded lipid particles at the neurorrhaphy site led to a
      significant increase in the density of regenerating axons as well as to an
      accelerated recovery of both muscle tropism and motor function. The
      electrophysiological results demonstrated a decrease of the threshold, a lower
      latency, and a higher conduction velocity in the Perineurin-treated animals.
      CONCLUSIONS: The results of the present study suggest that local administration
      of Perineurin might have a therapeutic potential for improving the postoperative
      outcome after microsurgical nerve reconstruction in patients.

PMID- 20042790
TI  - Rehabilitation of hemispatial neglect: A randomized study using either arm
      activation or visual scanning training.
AB  - PURPOSE: Hemispatial neglect, a failure to orient to the contralateral side of
      the lesion, is a disabling disorder after stroke. Previously arm activation
      combined with visual training or visual scanning training were found effective in
      rehabilitation of hemispatial neglect. The aim of this study was to determine
      whether left arm activation alone could be sufficient to produce a long lasting
      amelioration of neglect comparable to the effect obtained with traditional visual
      scanning training. METHODS: Twelve neglect patients less than six months from
      stroke were randomized either into 20-30 hours of left arm activation training or
      10 hours of traditional visual scanning training as a part of a comprehensive
      rehabilitation program. All patients received 48~hours of therapy during the 3
      week rehabilitation. RESULTS: Visual neglect of the arm activation group
      recovered significantly in the conventional subtests of the Behavioural
      Inattention Test both post-rehabilitation and at 6-months follow-up. The
      improvement of the visual scanning training group was almost significant at the
      end of the rehabilitation and significant by the follow-up. The behavioural
      neglect observed in the Catherine Bergego Scale was alleviated nearly
      significantly at the post-rehabilitation in both groups. The effect was
      maintained in the arm activation group at 6-months. CONCLUSION: The arm
      activation training appears beneficial even without supplementary visual neglect
      rehabilitation, although the traditional visual scanning training may have
      further effects in cognition.

PMID- 20042791
TI  - Comparison of two types of Constraint-Induced Movement Therapy in chronic stroke
      patients: A pilot study.
AB  - Several studies showed that Constraint-Induced Movement Therapy (CIMT) leads to a
      lasting improvement of upper extremity function in chronic stroke patients. The
      original technique includes an intensive 2-week program with 6 hours of daily
      physiotherapy. Due to high expenses it is difficult to implement this concept in
      outpatient care. PURPOSE: The objective of this study was to evaluate the effects
      of a 4-week homebased CIMT program among chronic stroke patients and to compare
      them with a 2-week CIMT program, based on the original technique. METHODS: Seven
      adults with chronic stroke completed a newly developed variant of CIMT, performed
      at patients' homes (group1, CIMThome), supervised by an instructed family member,
      constraint of unaffected hand for a target of 60% of waking hours. The
      intervention was analysed with pre-, post-treatment and 6-month follow-up
      measurements. Effects on improvement in upper extremity function were compared
      with patients treated according to the original protocol (group2, CIMTclassic),
      supervised by a physiotherapist, constraint of unaffected hand for a target of
      90% of waking hours. RESULTS: Patients from both groups showed almost identical
      improvement of their motor function according to scores on the Wolf Motor
      Function Test (WMFT) and the Motor Activity Log (MAL) immediately after the
      treatment period as well as at follow-up after 6 months. CONCLUSIONS: Our study
      suggests that CIMThome is not only feasible but also as effective as CIMTclassic.
      This finding should be replicated in a larger prospective randomized trial to
      perform a non-inferiority analysis.

PMID- 20042792
TI  - Bio-Medical Materials and Engineering. Foreword.

PMID- 20042793
TI  - Platelet-derived growth factors for GMP-compliant propagation of mesenchymal
      stromal cells.
AB  - Stem cell-based therapies are a promising prospect for regenerative medicine.
      Particularly, human multipotent mesenchymal stromal cells (MSCs) are currently in
      focus regarding their regenerative and immune modulating capacities. An
      increasing number of clinical trials investigating MSC efficiency and safety are
      ongoing. Ex vivo propagation of human MSCs is considered to be a prerequisite for
      MSC therapy. The to date standard use of fetal bovine serum in cell culture bears
      risks including xenoimmunization and transmission of pathogens. Alternatively,
      human platelet-derived growth factors have been efficiently implemented into
      routine MSC expansion protocols. In compliance with good manufacturing practice
      we established an effective time- and resource-saving procedure for MSC
      propagation in an animal serum-free system. Bone marrow was seeded without
      manipulation directly in pooled human platelet lysate (pHPL) and L-glutamine
      supplemented minimum essential medium without antibiotics. Clinical scale
      expanded MSCs were harvested already after primary culture. MSC quality,
      identity, purity and function were assessed according to a defined panel of
      release criteria and comparative genomic hybridization was used to determine
      genomic stability. Because various potential risks of MSCs have recently been
      reported, further research is required to prove efficiency and long-term safety
      of human MSCs for cell therapy.

PMID- 20042794
TI  - Autologous bone marrow graft and treatment of delayed and non-unions of long
      bones: technical aspects.
AB  - This article reports the technique of percutaneous autologous bone marrow
      injection as a minimally invasive method alternative to open grafting techniques
      in the treatment of delayed unions and non-unions. Despite continuous advances in
      the treatment of long bone fractures, disturbances of healing processes remain a
      difficult challenge for orthopaedic surgeons. Percutaneous administration of
      substances with osteoinductive and osteogenic properties offers the advantage of
      decreased morbidity associated with the classic open grafting techniques. This
      makes it worth exploring before embarking on more extensive open surgery. The
      authors present the main technical stages of the percutaneous bone marrow
      grafting (bone marrow aspiration, concentration, intra-osseous re-injection and
      post-operative protocol) with a short literature review about this topic.

PMID- 20042795
TI  - Optimization of a culture medium for the differentiation of preadipocytes into
      adipocytes in a monolayer.
AB  - Our objective was to optimize a medium for preadipocyte differentiation into
      adipocytes. METHODS: The differentiation medium contains fixed components as well
      as 7 variable ones. To perform this study, different experiments were designed
      and the study was carried out in 4 stages. The first two stages tested the
      influence of serum, dexamethasone, hydrocortisone and an cAMP activator. In the
      third stage, two new variables were added: rosiglitazone and insulin. In the
      final stage, the medium selected in stage 3 was validated. The differentiation
      selection criteria consisted of the number of mature adipocytes and adiponectin
      secretion. RESULTS: We have shown that each variable was indispensable and that
      positive interactions occurred between some variables. No negative interactions
      were found and it was possible to optimize the concentration of each variable.
      CONCLUSIONS: We selected the following medium, which provides optimal adipocyte
      size and adiponectin secretion: DMEM/HAMF12+10% Foetal Clone Serum (FCS)+2 nM
      triiodothyronine+10 nM hydrocortisone +0.5 mM IsoButyl Methyl Xanthine (IBMX)+500
      nM dexamethasone+1 microM rosiglitazone+0.15 UI/ml insulin+antibiotics.

PMID- 20042796
TI  - Quantification of residual dimethylsulfoxide after washing cryopreserved stem
      cells and thawing tissue grafts.
AB  - Dimethylsulfoxide (DMSO) is a cryoprotective substance often used to allow long
      term storage of stem cells or tissue grafts. However, a high frequency of adverse
      events is associated with the infusion of thawed cells. These events are in part
      due to DMSO, leading many cell therapy facilities to introduce a washing step
      before the delivery of the grafts. The lack of method for evaluating the residual
      quantities of this substance in the reinfused cells led us to develop a
      technique, based on capillary zone electrophoresis for assaying DMSO. The
      cryoprotectant was measured in 55 hematopoietic stem cell grafts, 6 parathyroids
      and 5 blood vessels immediately after thawing and after washing or bathing in a
      saline solution. The results showed that DMSO reduction in stem cell grafts
      reached more than 90% after the washing procedure. Furthermore, this study has
      shown that 2 washing steps significantly improved DMSO elimination as compared to
      1 washing step. For parathyroids and blood vessels, bathing the tissues after
      thawing in a saline solution allowed more than 95% DMSO reduction. This study
      demonstrated that the technique of DMSO measurement used here, is simple and
      feasible on complex matrices such as protein samples after dilution. It is an
      appropriate method for residual quantification of the cryoprotectant before
      graft.

PMID- 20042797
TI  - In vitro initial expansion of mesenchymal stem cells is influenced by the culture
      parameters used in the isolation process.
AB  - In the last years, there were many studies based on the use of human bone marrow
      mesenchymal stem cells (hMSCs) in cell therapy and tissue engineering. Although
      hMSCs can be easily obtained and expanded in culture, a large number of cells are
      often needed. The expansion of hMSCs depends on the culture conditions, such as
      media, cell density or culture flasks. Moreover, growth factors are often added
      to improve cell proliferation. In this study, we compared the effect of two
      culture media (DMEM and alpha-MEM), two culture flasks (75 or 25 cm2) and two
      different mononuclear cell seeding densities (1 x 10(4) or 5 x 10(4) MNC/cm2) on
      the isolation of hMSCs from bone marrow samples and analyzed if the isolation
      conditions affected the expansion of these cells in the first two passages.
      Experiments were performed without the addition of exogenous growth factors. Our
      results showed that alpha-MEM is the optimal culture medium for both, isolation
      and expansion of mesenchymal stem cells. Moreover, the cell seeding density of
      50,000 MNC/cm2 in 25 cm2 culture flasks seems to be the best condition for the
      isolation step.

PMID- 20042798
TI  - Subchondral bone in osteoarthritis physiopathology: state-of-the art and
      perspectives.
AB  - Osteoarthritis (OA) is the most common form of arthritic disease, and it is a
      major cause of disability and impaired quality of life in the elderly. A hallmark
      of the disease is progressive degeneration of articular cartilage and subsequent
      joint space narrowing. However, OA is a complex disease not limited to cartilage
      degeneration, but involving also synovial membrane and subchondral bone, thereby
      presenting alternatives approaches for treatment. In this paper, we propose a
      short review of the recent advances in the understanding of the role played by
      subchondral bone in OA.

PMID- 20042799
TI  - In situ endothelialization potential of a biofunctionalised nanocomposite
      biomaterial-based small diameter bypass graft.
AB  - Endothelial dysfunction or the lack of an endothelium associated with
      cardiovascular grafts is a major cause of graft failure which is linked to
      thrombosis and related complications. This study was aimed to (1)
      biofunctionalise a nanocomposite biomaterial, Polyhedral Oligomeric
      silsesquioxane modified polycarbonate urea-urethane (POSS-PCU), based small
      diameter vascular graft and to (2) induce endothelialization with EPC containing
      monocytes, which were extracted from peripheral blood. (1) Biofunctionalisation
      of the nanocomposite polymer: bioactive RGD peptide, which is a functional domain
      of an extracellular matrix component, fibronectin, was synthesised using fmoc
      chemistry. A lauric acid hydrophobic "tail" was attached to optimise the RGD
      orientation on the biomaterial. The peptide was cross linked to POSS-PCU. The
      presence of RGD on the nanocomposite was tested with water contact angle
      measurements and specificity tests were carried out with the peptide RAD (2)
      Progenitor cells were extracted from peripheral blood of adult healthy volunteers
      and cultured on porous biofunctionalised nanocomposite polymer under static
      conditions. Cells were also introduced to a circuit to which the grafts are
      connected and non static pulsatile flow conditions were introduced after 72 h
      following cell introduction. The degree of cell growth was tested with Alamar
      Blue assay. Endothelialization was confirmed with SEM and by immunostaining for
      endothelial cell markers, CD34, CD31 and eNOS. Water contact angle measurement
      indicated that biofunctionalisation had increased hydrophilicity of the
      nanocomposite polymer. Alamar blue indicated a greater presence of cells on
      biofunctionalised nanocomposite and this relative increase in cell viability was
      specific to RGD as confirmed with RAD peptides. SEM provided evidence for
      endothelial cell morphology and this was confirmed with endothelial cell markers
      with immunostaining. Biofunctionalised nanocomposite polymer-based small diameter
      bypass graft demonstrated the potential for relatively rapid endothelialization
      from cells extracted from peripheral blood.

PMID- 20042800
TI  - Extracellular matrices as advanced scaffolds for vascular tissue engineering.
AB  - An alternative non-vascular extracellular material was obtained by
      decellularisation of porcine urinary bladder and examined for its potential as
      scaffold for vascular tissue engineering. Analysis using Scanning Electron
      Microscopy (SEM), Atomic Force Microscopy (AFM) and Laser Scanning Microscopy
      (LSCM) showed a porous interconnective microarchitecture, an abundance of well
      preserved fibers on the abluminal side and a micropatterned flat luminal surface.
      Uniaxial tensile testing revealed a strength of 1.9+/-0.3 MPa for the rehydrated
      material in a phosphate buffered saline medium for the ECM-UBM sheet and these
      results comparable to those of native artery of a middle aged human.
      Multilamination of the UBM increases the tensile properties in general (9+/-0.45
      MPa for 2 layer, 30+/-0.6 MPa for 4 layers construct), with no effect on
      elongation capacities (38-40%) of the material. Contact-angle measurements
      indicated that the ECM-UBM surface exhibited a hydrophylic characteristic and
      better wettability than any vascular synthetic materials. Comparison of the
      initial adhesion in the multiplayer ECM constructs was evaluated and was found
      not to be altered by the preparation. The HAECs and HSMC shown an excellent
      adherence, spread and proliferation on the ECM-UBM material with the preservation
      of the cell phenotype. The level of MMP-1 and MMP-9 produced by endothelial cells
      was evaluated in this study and provides some data on the remodelling capacity of
      the scaffold. Vascular cell seeded-UBM constructs may also provide a suitable and
      affordable in vitro model for cell-physiology and drug development studies, which
      may elucidate to the mechanisms of vascular disease formation, and its prevention
      and treatment.

PMID- 20042801
TI  - Polyelectrolyte multilayer films promote human cord blood stem cells
      differentiation into mature endothelial cells exhibiting a stable phenotype.
AB  - BACKGROUND: recent studies in bio-engineering have showed the influence of
      Polyelectrolyte Multilayer (PEM) films on endothelial cells (ECs), especially
      poly(sodium-4-styrene-sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH).
      They were tested either with human mature ECs or rabbit immature endothelial
      progenitor cells (EPCs), but never on human EPCs. In view to obtain an EC covered
      surface, human cord blood (HCB) EPCs were cultivated on PSS/PAH films. MATERIAL
      AND METHODS: PEMs were obtained by 7 alternate depositions of cationic PAH and
      anionic PSS layers. HCB mononuclear cells were isolated by centrifugation through
      density gradient. 7 days after seeding on PEM, unattached cells were removed and
      adherent EPCs were cultivated in endothelial specific medium until P6. Appearance
      of CD31 and vWF was evaluated by confocal microscopy. RESULTS: EPCs not only
      successfully adhered on PEM, but also spread and proliferated. Moreover, cells
      differentiated into a typical endothelial cobblestone monolayer within 2 weeks.
      Immunostaining of CD31 and vWF confirmed the formation of an EC-like confluent
      monolayer. Furthermore, these cells showed after 6 passages a good phenotypic
      stability while reseeded on the PEM film. CONCLUSION: these results show an easy
      way to obtain mature ECs from human stem cells, which may open new applications
      for a scaffold cellularization in tissue bio-engineering.

PMID- 20042802
TI  - Arterial and venous thromboembolic events during anti-TNF therapy: a study of 85
      spontaneous reports in the period 2000-2006.
AB  - BACKGROUND: Systemic inflammation such as rheumatoid arthritis (RA) and Crohn's
      disease (CD) may be responsible for vascular comorbidity. TNF-alpha blockade was
      expected to lower these comorbidities but several cases of arterial and venous
      thromboembolic events (TE) have been reported. OBJECTIVES: The aim of this work
      was to study retrospectively the main characteristics of spontaneously notified
      TNF-alpha blockers related TE over a 7-year period. METHODS: TE related to
      infliximab, etanercept and adalimumab spontaneously notified to the French
      adverse drug reporting system database between January 2000 and December 2006
      were analyzed. Separate analysis of arterial TE and venous TE was performed. Risk
      factors for each category of TE were assessed with consensual criteria. RESULTS:
      85 TE were analyzed, representing 4.5% of all the spontaneously notified adverse
      reactions of the 3 TNF-alpha blockers in the database. 42 were arterial events
      and 43 were venous events. The incidence was not significantly different between
      the 3 TNF-alpha blockers. Mean delay of TE onset after treatment initiation was
      10.6 months. It was significantly shorter for etanercept (6.1 months, p=0.001)
      especially for venous TE (2.4 months). 16 among the 42 patients with arterial TE
      had 2 or more risk factors whereas 39 among the 43 patients with venous TE had no
      RF or only one. Most of patients (79/85) received concomitant systemic
      corticosteroids and/or methotrexate and/or COX-2 selective inhibitors. 23
      patients had been investigated for autoimmunity, 13 had antinuclear and/or
      antiphospholipid antibodies. Main limitations of this study were underreporting
      and heterogeneous report contents. CONCLUSION: Despite its limitations, this
      study suggests that venous TE could be favoured by TNF-alpha blockers therapy
      since they occurred in patients with no or few risk factors for venous
      thrombosis. However, this needs to be more evaluated by controlled studies.

PMID- 20042803
TI  - Characterisation of human fibroblasts as keratinocyte feeder layer using p63
      isoforms status.
AB  - Large-scale culture of primary keratinocytes allows the production of large
      epidermal sheet surfaces for the treatment of extensive skin burns. This method
      is dependent upon the capacity to establish cultures of proliferating
      keratinocytes in conditions compatible with their clonal expansion while
      maintaining their capacity to differentiate into the typical squamous pattern of
      human epidermis. Feeder layers are critical in this process because the
      fibroblasts that compose this layer serve as a source of adhesion, growth and
      differentiation factors. In this report, we have characterise the expression
      patterns of p63 isoforms in primary keratinocytes cultured on two different
      feeder layer systems, murine 3T3 and human fibroblasts. We show that with the
      latter, keratinocytes express a higher ratio of Delta N to TAp63 isoform, in
      relation with higher clonogenic potential. These results indicate that human
      fibroblasts represent an adequate feeder layer system to support the culture of
      primary human keratinocytes.

PMID- 20042804
TI  - Regulatory aspects of cellular therapy product in Europe: JACIE accreditation in
      a processing facility.
AB  - In 1997, the Joint Accreditation Committee ISCT & EBMT (JACIE) was created. The
      following year, it approved the first edition of standards for haemopoietic
      progenitor cell collection, processing and transplantation. The purpose of the
      standards is to ensure a minimal level of quality, alertness and homogeneity in
      the implementation of autologous and allogeneic haemopoietic stem cell
      transplantation (HSCT) programme in onco-hematology. The acquisition of
      accreditation is based upon the system of examination by trained medical
      professionals according to countries endorsements with the national regulation
      obligations applicable to HSCT. In 2008, the fourth edition has been launched.
      The range of application of the standards comprises both donors and recipients,
      and all phases of collection, processing, storage and administration of
      haemopoietic progenitor cells. Among the accredited processing facilities, a few
      have been integrated JACIE standards into their existing management quality
      system which is inspected by national health authority. In France, the comparison
      between JACIE standards and the good manufacturing practices of cellular therapy
      product reveals some common points and some differences to apply.

PMID- 20042807
TI  - Accreditation standards of DO- and MD-granting medical schools: an incomplete
      comparison.

PMID- 20042809
TI  - More about the teaching of scientific writing.

PMID- 20042810
TI  - More about the teaching of scientific writing.

PMID- 20042811
TI  - Health advocacy training: now is the time to develop physician leaders.

PMID- 20042812
TI  - Commentary: Conflict of interest policies: an opportunity for the medical
      profession to take the lead.
AB  - Articles in this issue by Steinman and colleagues, Dubovsky and colleagues, and
      Camilleri and Parke illustrate how academic health centers (AHCs) and
      professional membership organizations can take the lead in improving conflict of
      interest (COI) policies. In this commentary, the strategies explored in these
      articles are examined in the context of the Institute of Medicine (IOM) report,
      "Conflict of Interest in Medical Research, Education, and Practice," issued in
      April 2009. The author applauds the empirical research, educational efforts, and
      guidelines development described in the three articles and relates them to
      specific recommendations in the IOM report. Important issues that deserve
      attention are making disclosure of financial relationships more specific and less
      burdensome, developing a model for continuing medical education that provides
      high-quality education without undue influence, addressing institutional
      conflicts of interest, and honoring the educational mission. The author concludes
      that these articles show that physician leaders, AHCs, and professional societies
      can continue to take the lead by developing, implementing, enforcing, evaluating,
      and improving thoughtful and effective COI policies.

PMID- 20042813
TI  - Commentary: CME and its role in the academic medical center: increasing
      integration, adding value.
AB  - Continuing medical education (CME), as it is currently structured, funded, and
      institutionalized, plays a marginal role in the academic medical center (AMC). In
      contrast, several models of more effective, integrated CME exist, and these
      enable the AMC to better achieve its potential in education, research, and health
      care delivery. Examples of such models are presented, emphasizing quality and
      performance improvement; regional, national, and public outreach; faculty and
      staff development; and research and scholarly activity. Although there are many
      reasons to maintain the status quo of CME programs, there are offsetting forces
      for change to be found in accreditation processes, movements toward maintenance
      of certification and licensure, and the need for the AMC to achieve higher
      quality standards. These models may offer a view of the potential of academic CME
      to be a major vehicle for the effective integration in quality, regional, and
      faculty development arenas, and as a scholarly and outcomes-oriented pursuit.
      Sitting at the right table and sufficiently integrated, CME holds real potential
      to help the AMC meet its multiple goals and missions.

PMID- 20042814
TI  - Commentary: Urgently needed: a safe place for self-assessment on the path to
      maintaining competence and improving performance.
AB  - Traditional continuing medical education (CME), necessary for keeping physicians
      current and competent, is insufficient in translating physician practice into
      better patient outcomes. CME, then, must be transformed from a system of episodic
      interventions to a more personalized, contextual, flexible, and targeted process
      within a continuing professional development framework. The core of this
      transformation must be a formal process of physician self-assessment.
      Unfortunately, health care providers tend toward inaccurate self-assessment,
      regardless of training, specialty, or manner of self-assessment. Therefore, the
      development of an external validation system conducted by credible, informal peer
      review in a safe environment is essential. Clinicians must be able to access
      practice and patient data without concerns about accuracy, timeliness,
      confidentiality, attribution, or unintended consequences. New analytical tools
      are also needed to illuminate the data compilations and present them in
      compelling, individualized, and comparative formats. However, such developmental
      work will not be possible without strong community leadership coordinating a
      collaboration of resources and a sharing of data. Ensuring physician competence
      has long been an issue for medical societies, state licensing boards, and others
      invested in improving patient care. Now it's time to get serious. Current efforts
      at massive health care reform provide the perfect opportunity to fully integrate
      physician self-assessment and performance improvement into the larger health care
      system through a continuing professional development model. Practitioners in CME
      have been far too complacent with the current practices. A shift to a focused and
      dedicated sense of urgency must occur to ensure physicians' continuous learning
      and change.

PMID- 20042815
TI  - Commentary: IDSA guidelines for improving the teaching of preclinical medical
      microbiology and infectious diseases.
AB  - Preclinical microbiology and infectious diseases courses too often primarily
      depend on PowerPoint lectures and notes, combined with multiple-choice tests, as
      their primary teaching tools. This strategy sets low expectations for students,
      encouraging short-term memory and discouraging understanding and long-term
      memory. These methods also fail to stimulate active participation, collaborative
      learning, and two-way communication with the professor, and they do not respect
      the students' diverse talents and ways of learning. The Infectious Diseases
      Society of America Preclinical Curriculum Committee proposes a new approach that
      emphasizes active learning and understanding and that addresses all of these
      failures. It consists of five components: (1) "Just-in-time" teaching that
      requires students to e-mail the answers to two general questions as well as any
      areas of misunderstanding to the instructor several hours before each lecture,
      (2) peer instruction or large-group sessions consisting of student teams of four
      who electronically answer a conceptual question before each major section of the
      lecture, (3) teaching from edited textbooks and Internet sources, (4) small-group
      discussions that emphasize pathogenesis and differential diagnosis, and (5) essay
      questions that encourage and test understanding in addition to recognition. A
      national consensus on factual content is proposed, with the goals of reducing
      information overload and minimizing requirements for excessive memorization.
      These strategies promise to enhance learning and rekindle interest in the field
      of infectious diseases. Other subspecialty organizations should create similar
      teaching guidelines that will encourage future medical students to bring a richer
      understanding of clinical and basic science to the bedside.

PMID- 20042816
TI  - Commentary: Mentoring the mentor: executive coaching for clinical departmental
      executive officers.
AB  - Departmental executive officers (DEOs), department chairs, and department heads
      in medical schools are often hired on the basis of their accomplishments in
      research as well as their skills in administration, management, and leadership.
      These individuals are also expected to be expert in multiple areas, including
      negotiation, finance and budgeting, mentoring, and personnel management. At the
      same time, they are expected to maintain and perhaps even enhance their personal
      academic standing for the purposes of raising the level of departmental and
      institutional prestige and for recruiting the next generation of physicians and
      scientists. In the corporate world, employers understand the importance of
      training new leaders in requisite skill enhancement that will lead to success in
      their new positions. These individuals are often provided with extensive
      executive training to develop the necessary competencies to make them successful
      leaders. Among the tools employed for this purpose are the use of personal
      coaches or executive training courses. The authors propose that the use of
      executive coaching in academic medicine may be of benefit for new DEOs.
      Experience using an executive coach suggests that this was a valuable growth
      experience for new leaders in the institution.

PMID- 20042817
TI  - Programs for developing the pipeline of early-career geriatric mental health
      researchers: outcomes and implications for other fields.
AB  - This report summarizes the findings and recommendations of an expert consensus
      workgroup that addressed the endangered pipeline of geriatric mental health (GMH)
      researchers. The workgroup was convened at the Summit on Challenges in
      Recruitment, Retention, and Career Development in Geriatric Mental Health
      Research in late 2007. Major identified challenges included attracting and
      developing early-career investigators into the field of GMH research; a shortfall
      of geriatric clinical providers and researchers; a disproportionate lack of
      minority researchers; inadequate mentoring and career development resources; and
      the loss of promising researchers during the vulnerable period of transition from
      research training to independent research funding. The field of GMH research has
      been at the forefront of developing successful programs that address these issues
      while spanning the spectrum of research career development. These programs serve
      as a model for other fields and disciplines. Core elements of these
      multicomponent programs include summer internships to foster early interest in
      GMH research (Summer Training on Aging Research Topics-Mental Health Program),
      research sponsorships aimed at recruitment into the field of geriatric psychiatry
      (Stepping Stones), research training institutes for early career development
      (Summer Research Institute in Geriatric Psychiatry), mentored intensive programs
      on developing and obtaining a first research grant (Advanced Research Institute
      in Geriatric Psychiatry), targeted development of minority researchers (Institute
      for Research Minority Training on Mental Health and Aging), and a Web-based
      clearinghouse of mentoring seminars and resources (MedEdMentoring.org). This
      report discusses implications of and principles for disseminating these programs,
      including examples of replications in fields besides GMH research.

PMID- 20042818
TI  - Survey of care for the underserved: a control group study of practicing
      physicians who were graduates of The Ohio State University College of Medicine
      premedical postbaccalaureate training program.
AB  - PURPOSE: Multiple publications describe short- term and intermediate outcomes of
      premedical postbaccalaureate programs (PBPs). However, the authors could find no
      control group studies reporting the service provided by graduates of PBPs to
      patients who are medically indigent (e.g., on Medicaid or uninsured) and/or poor.
      The authors explored the relationship between successful completion of a
      midwestern PBP and providing care for the underserved. METHOD: In 2008, the
      authors surveyed 1996-2002 graduates of The Ohio State University College of
      Medicine who had been in practice for at least one year about their current
      practice population. The authors compared two groups: (1) physicians who
      completed the PBP and (2) a stratified random control group of physicians who
      graduated from the same medical school, in the same graduating classes, but did
      not participate in the PBP. RESULTS: The survey return rate was 70.9% (73/103).
      Findings suggest that PBP graduates were more likely to be practicing medicine in
      a federally designated underserved area (29.4% versus 5.1%, P < .009) or
      providing service where 40% or more of the patients were medically indigent or
      poor (67.6% versus 33.3%, P < .003). PBP graduates were also more likely to be
      volunteering their services to patients who were indigent (47.1% versus 10.3%, P
      < .001). CONCLUSIONS: This is likely the first control group study demonstrating
      the increased likelihood of graduates of a PBP providing health care to patients
      who are medically indigent and/or poor.

PMID- 20042819
TI  - Increasing the ranks of academic researchers in mental health: a multisite
      approach to postdoctoral fellowship training.
AB  - This report highlights the use of multisite training for psychiatry and
      psychology postdoctoral fellows developing careers in academic clinical research
      in the field of mental health. The objective is to describe a model of training
      for young investigators to establish independent academic clinical research
      careers, including (1) program structure and eligibility, (2) program goals and
      development of a multisite curriculum, (3) use of technology for implementing the
      program across multiple sites, and (4) advantages and challenges of this
      multisite approach. In 2000, in collaboration with the Veterans Affairs (VA)
      Mental Illness Research, Education and Clinical Centers (MIRECCs), the VA Office
      of Academic Affiliations launched the Special Fellowship Program in Advanced
      Psychiatry and Psychology. Each of the 10 currently participating VA sites across
      the United States is affiliated with a MIRECC and an academic medical
      institution. In the first five years of this fellowship program, 83 fellows (34
      psychiatrists and 49 psychologists) have participated. The success of this
      multisite approach is evidenced by the 58 fellows who have already graduated from
      the program: 70% have entered academic clinical research positions, and over 25
      have obtained independent extramural grant support from the VA or the National
      Institutes of Health. Multisite training results in a greater transfer of
      knowledge and capitalizes on the nationwide availability of experts, creating
      unique networking and learning opportunities for trainees. The VA's multisite
      fellowship program plays a valuable role in preparing substantial numbers of
      psychiatry and psychology trainees for a range of academic clinical research and
      leadership positions in the field of mental health.

PMID- 20042821
TI  - The prevalence and practice of academies of medical educators: a survey of U.S.
      medical schools.
AB  - PURPOSE: Academies of medical educators can be defined as formal organizations of
      academic teaching faculty recognized for excellence in their contributions to
      their school's education mission and who, as a group, serve specific needs of the
      institution. The authors studied the characteristics of academies, including the
      processes for admission, selection, and retention of academy members; the types
      of faculty who are academy members; program goals; benefits offered by academies
      to the individual and to the institution; funding sources and amounts; and the
      rapid increase in academies since 2003. METHOD: In 2008, the authors sent an
      online questionnaire to 127 U.S. medical schools. Responses were analyzed using
      descriptive statistics. To determine differences between groups, multivariate
      analysis of variance was performed. Correlation analysis (Pearson r) was used to
      identify association between variables. Effect size was determined using eta
      squared (eta2). RESULTS: Thirty-six of the 122 responding schools (96% response
      rate) reported having academies; 21 schools had initiated academies since 2003,
      and 33 schools were planning or considering academies. There was a statistically
      significant difference between academies established before 2004 and in 2004
      regarding benefits offered to individuals, membership terms and maintenance
      requirements, and goals. CONCLUSIONS: Rogers' theory of the diffusion of
      innovation may explain the recent spread of academies. When beginning or
      reexamining existing academy programs, institutions should consider goals,
      application process, benefits offered to members as well as the institution,
      expendable resources, and means of support, because the final product depends on
      the choices made at the beginning.

PMID- 20042823
TI  - The mindsets of medical education leaders: how do they conceive of their work?
AB  - PURPOSE: How a leader perceives his or her organization affects that individual's
      decision making and beliefs about the best way to influence it. The goal of this
      study was to understand how medical education leaders conceive of their work.
      METHOD: The first author interviewed 16 medical education leaders in the Faculty
      of Medicine at the University of Toronto from June 2005 until February 2006. The
      sample represented different practice contexts to ensure a diverse overview of
      experiences. Using the theoretical framework of Bolman and Deal, the authors
      examined and described the perceptual frames through which these leaders perceive
      their endeavors. Transcripts were analyzed and then mapped onto Bolman and Deal's
      four cognitive lenses (i.e., frames). RESULTS: Fourteen of the 16 leaders used
      all cognitive frames. The human resource perspective was favored by all
      participants, followed closely by the symbolic (14/16) and political (14/16).
      Although most attended to the structural frame (14/16), only three placed any
      significant emphasis on it. In addition to identifying and describing the
      elements of this typology for medical education leadership, a new frame emerged
      of assessing interpersonal and work style in order to determine how to socially
      situate individuals. CONCLUSIONS: This study uniquely contributes by supporting
      the utility of the Bolman and Deal typology in the medical education context and
      supports the value for leaders to reflect on their organizational work from a
      variety of perspectives (including the frames). Medical education leadership
      development programs need to attend to enhancing the awareness of these
      perspectives.

PMID- 20042824
TI  - Locked-in: listening to save a life.

PMID- 20042825
TI  - Perspective: Physician advocacy: what is it and how do we do it?
AB  - Many medical authors and organizations have called for physician advocacy as a
      core component of medical professionalism. Despite widespread acceptance of
      advocacy as a professional obligation, the concept remains problematic within the
      profession of medicine because it remains undefined in concept, scope, and
      practice. If advocacy is to be a professional imperative, then medical schools
      and graduate education programs must deliberately train physicians as advocates.
      Accrediting bodies must clearly define advocacy competencies, and all physicians
      must meet them at some basic level. Sustaining and fostering physician advocacy
      will require modest changes to both undergraduate and graduate medical education.
      Developing advocacy training and practice opportunities for practicing physicians
      will also be necessary. In this article, as first steps toward building a model
      for competency-based physician advocacy training and delineating physician
      advocacy in common practice, the authors propose a definition and, using the
      biographies of actual physician advocates, describe the spectrum of physician
      advocacy.

PMID- 20042827
TI  - Can academic departments maintain industry relationships while promoting
      physician professionalism?
AB  - The authors describe the development of a comprehensive policy for relationships
      of full-time and volunteer faculty and residents with industry. The underlying
      philosophy was that an academic approach to relations with industry that
      emphasizes objective outcomes and internal change will be more effective than
      rote restrictions on behavior that assume that physicians cannot learn new
      behaviors and that are impossible to enforce. The policy, developed through much
      discussion and debate with stakeholders, involves elimination of industry
      supplied meals, gifts, and favors; integration of industry-sponsored and academic
      research; education of faculty and residents about the ways in which industry
      marketing influences clinical decision making; and comprehensive disclosure by
      faculty, including to patients, of financial interests in industry. At occasional
      points in the psychopharmacology curriculum and at a departmental "pharma
      symposium," industry representatives or industry-sponsored guest speakers are
      allowed to present peer-reviewed articles followed by comments by a faculty
      member with relevant expertise about aspects of the presentation that are
      accurate or misleading and by a general discussion of research and clinical
      implications of the research and the manner in which it is presented. Adherence
      to new protocols has been high because faculty and residents participated in
      developing them and are involved in their implementation. Acceptance by industry
      representatives has been variable. Experience with this approach suggests that it
      is possible to develop a collaborative relationship with industry that maintains
      appropriate boundaries between industry and academia.

PMID- 20042828
TI  - Commercial influence and learner-perceived bias in continuing medical education.
AB  - PURPOSE: To directly examine the relationship between commercial support of
      continuing medical education (CME) and perceived bias in the content of these
      activities. METHOD: Cross-sectional study of 213 accredited live educational
      programs organized by a university provider of CME from 2005 to 2007. A standard
      question from course evaluations was used to determine the degree to which
      attendees believed commercial bias was present. Binomial regression models were
      used to determine the association between course features that may introduce
      commercial bias and the extent of perceived bias at those CME activities.
      RESULTS: Mean response rate for attendee evaluations was 56% (SD 15%). Commercial
      support covered 20%-49% of costs for 45 (21%) educational activities, and > or =
      50% of costs for 46 activities (22%). Few course participants perceived
      commercial bias, with a median of 97% (interquartile range 95%-99%) of
      respondents stating that the activity they attended was free of commercial bias.
      There was no association between extent of commercial support and the degree of
      perceived bias in CME activities. Similarly, perceived bias did not vary for 11
      of 12 event characteristics evaluated as potential sources of commercial bias, or
      by score on a risk index designed to prospectively assess risk of commercial
      bias. CONCLUSIONS: Rates of perceived bias were low for the vast majority of CME
      activities in the sample and did not differ by the degree of industry support or
      other event characteristics. Further study is needed to determine whether
      commercial influence persisted in more subtle forms that were difficult for
      participants to detect.

PMID- 20042829
TI  - The effect of industry support on participants' perceptions of bias in continuing
      medical education.
AB  - PURPOSE: To obtain prospective evidence of whether industry support of continuing
      medical education (CME) affects perceptions of commercial bias in CME activities.
      METHOD: The authors analyzed information from the CME activity database (346 CME
      activities of numerous types; 95,429 participants in 2007) of a large,
      multispecialty academic medical center to determine whether a relationship
      existed among the degree of perceived bias, the type of CME activity, and the
      presence or absence of commercial support. RESULTS: Participants per activity
      ranged from 1 to 3,080 (median: 276). When asked the yes/no question, "Overall,
      was this activity satisfactorily free from commercial bias?" 97.3% to 99.2%
      (mean: 98.4%) of participants answered "yes." In responding on a four-point scale
      to the request, "Please rate the degree to which this activity met the
      Accreditation Council for Continuing Medical Education requirement that CME
      activities must be free of commercial bias for or against a specific product,"
      95.8% to 99.3% (mean: 97.2%) of participants answered "excellent" or "good." When
      analyzed by type of funding relative to commercial support--none (149), single
      source (79), or multiple source (118)--activities were deemed to be free of
      commercial bias by 98% (95% CI: 97.3, 98.8), 98.5% (97.5, 99.5), and 98.3% (97.4,
      99.1) of participants, respectively. None of the comparisons showed statistically
      significant differences. CONCLUSIONS: This large, prospective analysis found no
      evidence that commercial support results in perceived bias in CME activities.
      Bias level seem quite low for all types of CME activities and is not
      significantly higher when commercial support is present.

PMID- 20042830
TI  - Perspective: Conflict of interest and professional organizations: considerations
      and recommendations.
AB  - There are differences in conflicts of interest (COIs) in professional
      organizations compared with academic medical centers. The authors discuss nine
      major questions pertaining to industry relationships of professional
      organizations: (1) What makes COI management different in professional membership
      organizations? (2) What COI challenges are specific to professional
      organizations? (3) What are potential impacts of perceived or real COIs involving
      professional organizations and the management of COIs? (4) Is regulation
      necessary, or should professional organizations proactively resolve COI issues
      independently? (5) Are guidelines portable from academic medical centers to
      professional organizations? (6) What approaches may be considered for managing
      COIs of the organization's leaders? (7) What approaches are reasonable for
      managing COI issues at professional meetings? (8) What approaches are important
      for integrity of educational programs, publications, and products? and (9) What
      approaches are reasonable for managing and enforcing COI guidelines on an ongoing
      basis? Responses to these questions focus on four principles: First, a code of
      ethics governing general behavior of members and safeguarding the interest of
      patients must be in place; second, the monitoring and management of COI for
      leadership, including, in some cases, recusal from certain activities; third, the
      pooling and consistent, transparent management of unrestricted grants from
      corporate sponsors; and, fourth, the management of industry marketing efforts at
      membership meetings to ensure their appropriateness. The perspectives offered are
      intended to encourage individuals and learned bodies to further study and provide
      commentary and recommendations on managing COIs of a professional organization.

PMID- 20042831
TI  - Medicine and the arts. Urging normalcy: Allie (20-year-old male-to-female) and
      former girlfriend. 2008. Commentary.

PMID- 20042833
TI  - Burnout and serious thoughts of dropping out of medical school: a multi
      institutional study.
AB  - PURPOSE: Little is known about students who seriously consider dropping out of
      medical school. The authors assessed the severity of thoughts of dropping out and
      explored the relationship of such thoughts with burnout and other indicators of
      distress. METHOD: The authors surveyed medical students attending five medical
      schools in 2006 and 2007 (prospective cohort) and included two additional medical
      schools in 2007 (cross-sectional cohort). The survey included questions about
      thoughts of dropping out, life events in the previous 12 months, and validated
      instruments evaluating burnout, depression symptoms, and quality of life (QOL).
      RESULTS: Data were provided by 858 (65%) students in the prospective cohort and
      2,248 (52%) in the cross-sectional cohort. Of 2,222 respondents, 243 (11%)
      indicated having serious thoughts of dropping out within the last year. Burnout
      (P < .0001), QOL (P < .003 each domain), and depressive symptoms (P < .0001) at
      baseline predicted serious thoughts of dropping out during the following year.
      Each one-point increase in emotional exhaustion and depersonalization score and
      one-point decrease in personal accomplishment score at baseline was associated
      with a 7% increase in the odds of serious thoughts of dropping out during the
      following year. On subsequent confirmatory multivariable analysis, low scores for
      personal accomplishment, lower mental and physical QOL, and having children were
      independent predictors of students having serious thoughts of dropping out during
      the following year. CONCLUSIONS: Approximately 11% of students have serious
      thoughts of dropping out of medical school each year. Burnout seems to be
      associated with increased likelihood of serious thoughts of dropping out.

PMID- 20042835
TI  - A comprehensive medical student wellness program--design and implementation at
      Vanderbilt School of Medicine.
AB  - Research suggests that student burnout and mental illness are increasing in U.S.
      medical schools. In response, students and administrators developed the
      Vanderbilt Medical Student (VMS) Wellness Program to promote student health and
      well-being through coordination of many new and existing resources. This program
      consists of three core components: The Advisory College Program, The Student
      Wellness Committee, and VMS LIVE. Each of the core components includes separate
      and unique individual programs, but each of these three components collaborates
      with the other two to accomplish the broad wellness goal of maximizing student
      health, happiness, and potential. The VMS Wellness Program has had early success
      with substantial growth and outstanding student buy-in since its inception in
      2005. Preliminary data indicate that nearly every student has participated in at
      least two components of the VMS Wellness Program. In addition to participation,
      student response has been highly satisfactory, as evidenced by their positive
      feedback. The VMS Wellness Program is the first published model of a
      comprehensive medical student wellness initiative. The development and design of
      the program described in this article may serve as a framework for other
      institutions.

PMID- 20042836
TI  - Medical students' experiences of moral distress: development of a web-based
      survey.
AB  - PURPOSE: To develop an instrument for measuring moral distress in medical
      students, measuring the prevalence of moral distress in a cohort of students, and
      identifying the situations most likely to cause it. Moral distress, defined as
      the negative feelings that arise when one knows the morally correct thing to do
      but cannot act because of constraints or hierarchies, has been documented in
      nurses but has not been measured in medical students. METHOD: The authors
      constructed a survey consisting of 55 items describing potentially distressing
      situations. Responders rated the frequency of these situations and the intensity
      of distress that they caused. The survey was administered to 106 fourth-year
      medical students during a three-week period in 2007; the response rate was 60%.
      RESULTS: Each of the situations was experienced by at least some of the 64
      respondents, and each created some degree of moral distress. On average, students
      witnessed almost one-half of the situations at least once, and more than one
      third of the situations caused mild-to-moderate distress. The survey measured
      individual distress (Cronbach alpha = 0.95), which varied among the students.
      Whereas women witnessed potentially distressing situations significantly more
      frequently than did men (P = .04), men tended to become more distressed by each
      event witnessed (P = .057). CONCLUSIONS: Medical students frequently experience
      moral distress. Our survey can be used to measure aspects of the learning
      environment as well as individual responses to the environment. The variation
      found among student responses warrants further investigation to determine whether
      students at either extreme of moral distress are at risk of burnout or erosion of
      professionalism.

PMID- 20042837
TI  - What students learn about professionalism from faculty stories: an "appreciative
      inquiry" approach.
AB  - PURPOSE: To develop a method for teaching professionalism by enabling students
      and faculty members to share positive examples of professionalism in a
      comfortable environment that reflects the authentic experiences of physicians.
      Medical educators struggle with the teaching of professionalism. Professionalism
      definitions can guide what they teach, but they must also consider how they teach
      it, and constructs such as explicit role modeling, situated learning, and
      appreciative inquiry provide appropriate models. METHOD: The project consisted of
      students interviewing faculty members about their experiences with
      professionalism and then reflecting on and writing about the teachers' stories.
      In 2004, 62 students interviewed 33 faculty members, and 193 students observed
      the interviews. Using a project Web site, 36 students wrote 132 narratives based
      on the faculty's stories, and each student offered his or her reflections on one
      narrative. The authors analyzed the content of the narratives and reflections via
      an iterative process of independent coding and discussion to resolve
      disagreements. RESULTS: Results showed that the narratives were rich and
      generally positive; they illustrated a broad range of the principles contained in
      many definitions of professionalism: humanism, accountability, altruism, and
      excellence. The students' reflections demonstrated awareness of the same major
      principles of professionalism that the faculty conveyed. The reflections served
      to spark new ideas about professionalism, reinforce the values of
      professionalism, deepen students' relationships with the faculty, and heighten
      students' commitment to behaving professionally. CONCLUSIONS: Narrative
      storytelling, as a variant of appreciative inquiry, seems to be effective in
      deepening students' understanding and appreciation of professionalism.

PMID- 20042838
TI  - Medical students' professionalism narratives: a window on the informal and hidden
      curriculum.
AB  - PURPOSE: The aim of this study was to use medical students' critical incident
      narratives to deepen understanding of the informal and hidden curricula. METHOD:
      The authors conducted a thematic analysis of 272 stories of events recorded by
      135 third-year medical students that "taught them something about professionalism
      and professional values." Students wrote these narratives in a "professionalism
      journal" during their internal medicine clerkships at Indiana University School
      of Medicine, June through November 2007. RESULTS: The majority of students'
      recorded experiences involved witnessing positive embodiment of professional
      values, rather than breaches. Attending physicians and residents were the central
      figures in the incidents. Analyses revealed two main thematic categories. The
      first focused on medical-clinical interactions, especially on persons who were
      role models interacting with patients, families, coworkers, and colleagues. The
      second focused on events in the teaching-and-learning environment, particularly
      on students' experiences as learners in the clinical setting. CONCLUSIONS: The
      findings strongly suggest that students' reflective narratives are a rich source
      of information about the elements of both the informal and hidden curricula, in
      which medical students learn to become physicians. Experiences with both positive
      and negative behaviors shaped the students' perceptions of the profession and its
      values. In particular, interactions that manifest respect and other qualities of
      good communication with patients, families, and colleagues taught powerfully.

PMID- 20042839
TI  - Observation, reflection, and reinforcement: surgery faculty members' and
      residents' perceptions of how they learned professionalism.
AB  - PURPOSE: To explore perceptions of how professionalism is learned in the current
      academic environment. Professionalism is a core competency in surgery (as in all
      of medical practice), and its presence or absence affects all aspects of clinical
      education and practice, but the ways in which professional values and attitudes
      are best transmitted to developing generations of surgeons have not been well
      defined. METHOD: The authors conducted 34 semistructured interviews of individual
      surgery residents and faculty members at two academic institutions from 2004 to
      2006. Interviews consisted of open-ended questions on how the participants
      learned professionalism and what they perceived as challenges to learning
      professionalism. Two researchers analyzed the interview transcripts for emergent
      themes by using a grounded-theory approach. RESULTS: Faculty members' and
      residents' perceptions of how they learned professionalism reflected four major
      themes: (1) personal values and upbringing, including premedical education
      experiences, (2) learning by example from professional role models, (3) the
      structure of the surgery residency, and (4) formal instruction on
      professionalism. Of these, role modeling was the dominant theme: Participants
      identified observation, reflection, and reinforcement as playing key roles in
      their learning from role models and in distinguishing the sometimes blurred
      boundary between positive and negative role models. CONCLUSIONS: The theoretical
      framework generated out of this study proposes a focus on specific activities to
      improve professional education, including an active approach to role modeling
      through the intentional and explicit demonstration of professional behavior
      during the course of everyday work; structured, reflective self-examination; and
      timely and meaningful evaluation and feedback for reinforcement.

PMID- 20042840
TI  - Impact of peer assessment on the professional development of medical students: a
      qualitative study.
AB  - PURPOSE: Peer assessment can predict future academic performance and provide
      medical students with reliable feedback about professionalism. It is unclear
      whether peer assessment fosters personal growth or transformations in attitudes
      or behaviors. The authors investigated what types of peer feedback students
      remember and what reactions or transformations students experience as a result of
      peer assessment. METHOD: In May 2005, the authors invited medical students from
      the second-year (n = 101) and fourth-year (n = 83) classes to provide narratives
      about how peer assessment affected their personal and professional development.
      All students had participated in peer assessment during required, formative
      comprehensive assessments. The authors analyzed responses using mixed qualitative
      quantitative methods. RESULTS: The 138 responses represented 82% and 69% of
      students from the fourth-year and second-year classes, respectively. Students
      recalled peer assessment content about both positive (e.g., teaching skills) and
      negative (e.g., overconfidence) qualities. Both positive (e.g., appreciation) and
      negative (e.g., anger) emotional reactions were reported. Many (67%) found peer
      assessment helpful, reassuring, or confirming of something they knew; 65%
      reported important transformations in awareness, attitudes, or behaviors because
      of peer assessment. Change was more likely when feedback was specific and
      described an area for improvement. Wholly negative responses to the peer
      assessment process were rare. CONCLUSIONS: Peer assessment can be a powerful tool
      to assess and encourage formation of professional behaviors, particularly the
      interpersonal dimensions. Participants should receive training to provide
      specific, constructive feedback. The institutional culture should emphasize
      safety around feedback, while committing to rewarding excellence and addressing
      concerning behaviors.

PMID- 20042841
TI  - Instructiveness of real patients and simulated patients in undergraduate medical
      education: a randomized experiment.
AB  - PURPOSE: Few studies have compared the instructiveness of real patient contacts
      with simulated patient (SP) contacts. Although most of these studies found no
      difference, students often comment that the instructiveness of both encounters is
      dissimilar. The aims of this study were to evaluate which contact (real patient
      or SP) is perceived as most instructive by students and which variables
      contribute to this. METHOD: The authors performed an experiment involving 163
      first-year medical students, randomized to having a real patient contact (n = 61)
      or SP contact (n = 102). Quantitative (questionnaires) and qualitative (focus
      groups) methods were used to evaluate the perceived instructiveness of the
      contact. RESULTS: The general instructiveness of both real patient contacts and
      SP contacts was marked high. Several differences between the evaluations of real
      patient contacts and SP contacts were found. For example, students considered
      real patient contacts less helpful in practicing communication skills and
      considered the real patients' feedback less relevant. The focus group interviews
      yielded explanations for many of the differences found. Students regarded real
      patients as more authentic. However, SPs were better informed about the purpose
      of the consultation and provided the student with more specific feedback.
      CONCLUSIONS: Students consider authenticity an important advantage of real
      patients. Their difficult recruitment is an important disadvantage, however, SPs
      have important advantages compared with real patients--for example, their
      feedback. The choice of real patient contacts or SP contacts for medical
      education depends on factors like the phase of the curriculum and the aim of the
      encounter.

PMID- 20042842
TI  - Virtual patients: ED-2 band-aid or valuable asset in the learning portfolio?
AB  - The challenge of planning a clinical clerkship curriculum is to create order from
      chaos. Fortunately, the Liaison Committee for Medical Education has thrown
      clerkship directors a lifeline by recognizing simulated learning experiences-
      including virtual patients--as equivalents to real-life clinical encounters for
      accreditation purposes. Although virtual patients offer a more consistent and
      learner-centered curriculum that provides greater practice opportunities and
      reduces the demand for busy clinical preceptors, going virtual does involve
      potential risks. Here, the authors discuss some of the pros and cons of virtual
      patients, especially the concerns that virtual learning experiences may not
      produce effective feedback and that learning may not transfer from the virtual to
      the clinical environment. To match teaching to different learning needs, the
      authors propose "adaptive feedback" whereby learners choose from three levels of
      feedback: seeing the correct diagnosis and patient outcomes, seeing an expert
      "trace," and/or meeting with their preceptor to discuss the case. Medical
      educators can facilitate automatic transfer of learning from the virtual to the
      clinical setting by making all aspects of the learning and retrieval environments
      as similar as possible and by integrating the virtual and clinical environments-
      thus sparing learners the burden of "forward reaching" transfer and providing an
      anchor for virtual learning experiences. Medical educators can promote
      intentional transfer of learning if they make the virtual learning environment
      both the place students practice their skills before clinical encounters and the
      place to which they return after clinical encounters to reflect on and improve
      their skills.

PMID- 20042843
TI  - Perspective: The doctor as performer: a proposal for change based on a
      performance studies paradigm.
AB  - The authors recognize the pressing need for teaching methods that encourage
      empathy in both undergraduate and postgraduate medical curricula. While the
      useful application of theatrical acting techniques in medical education has been
      reported in major medical journals, these reports present an incomplete picture
      of these techniques and their potential importance to physician competence. The
      authors propose a broader understanding of performance theories and practices and
      a more nuanced appreciation of the experience and knowledge acquired through
      working with standardized patients and acting exercises. The academic discipline
      of performance studies offers a paradigm not only for teaching doctors how to
      "act" in a more truly empathetic and compassionate manner but also for analyzing,
      and thus evaluating and improving, human interactions in the medical environment.
      A complex understanding of performance is essential to the development of an
      empathetic imagination, a cognitive faculty that allows physicians to generate
      unique responses to given situations rather than employing reactions learned by
      rote in "communications training." The authors recommend the inclusion of a wide
      range of performance theories and practices alongside the ubiquitous presence, in
      medical schools and other physician education forums, of actors performing as
      standardized patients.

PMID- 20042844
TI  - An informatics-based tool to assist researchers in initiating research at an
      academic medical center: Vanderbilt Customized Action Plan.
AB  - The regulatory review and approval process is a significant part of the workflow
      associated with initiating clinical and translational research projects.
      Ambiguity concerning submission requirements and expected times associated with
      the review process can create additional work for research teams and ultimately
      delay important scientific projects. In an effort to provide assistance to
      investigators, we have developed an online interactive interface which elicits
      basic study characteristics for a single project and subsequently produces a list
      of required administrative applications needed for approval along with clear
      instructions concerning expectations from the research team. This system, the
      Vanderbilt Customized Action Plan (V-CAP), was launched in October 2006 and has
      been well received by researchers. In this article, the authors present (1) the V
      CAP project design, (2) a reference workflow associated with Vanderbilt policies
      and regulations, (3) the V-CAP metrics of use by Vanderbilt research teams, and
      (4) a list of recommendations for other academic centers considering a similar
      systems-based approach for helping researchers efficiently navigate processes
      related to regulatory approval. The informatics-systems-based approach of the V
      CAP is scalable to other academic medical centers and may serve as a useful model
      to help researchers navigate the complexity of the regulatory approvals process.

PMID- 20042845
TI  - Utility of the AAMC's Graduation Questionnaire to study behavioral and social
      sciences domains in undergraduate medical education.
AB  - PURPOSE: The Institute of Medicine (IOM) report on social and behavioral sciences
      (SBS) indicated that 50% of morbidity and mortality in the United States is
      associated with SBS factors, which the report also found were inadequately taught
      in medical school. A multischool collaborative explored whether the Association
      of American Medical Colleges Graduation Questionnaire (GQ) could be used to study
      changes in the six SBS domains identified in the IOM report. METHOD: A content
      analysis conducted with the GQ identified 30 SBS variables, which were narrowed
      to 24 using a modified Delphi approach. Summary data were pooled from nine
      medical schools for 2006 and 2007, representing 1,126 students. Data were
      generated on students' perceptions of curricular experiences, attitudes related
      to SBS curricula, and confidence with relevant clinical knowledge and skills. The
      authors determined the sample sizes required for various effect sizes to assess
      the utility of the GQ. RESULTS: The 24 variables were classified into five of six
      IOM domains representing a total of nine analytic categories with cumulative
      scale means ranging from 60.8 to 93.4. Taking into account the correlations among
      measures over time, and assuming a two-sided test, 80% power, alpha at .05, and
      standard deviation of 4.1, the authors found that 34 medical schools would be
      required for inclusion to attain an estimated effect size of 0.50 (50%). With a
      sample size of nine schools, the ability to detect changes would require a very
      high effect size of 107%. CONCLUSIONS: Detecting SBS changes associated with
      curricular innovations would require a large collaborative of medical schools.
      Using a national measure (the GQ) to assess curricular innovations in most areas
      of SBS is possible if enough medical schools were involved in such an effort.

PMID- 20042846
TI  - AM last page: Increasing workforce diversity.

PMID- 20042847
TI  - Recurrent TB: relapse or reinfection? The effect of HIV in a general population
      cohort in Malawi.
AB  - OBJECTIVE: To estimate rates of recurrent tuberculosis due to reinfection and
      relapse, by HIV status, in a general population. DESIGN: Long-term cohort study
      in Karonga district, rural Malawi. METHODS: All tuberculosis patients with
      culture-proven disease in Karonga district were followed up after treatment. HIV
      testing was offered and all Mycobacterium tuberculosis isolates were
      fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease
      episodes were compared to distinguish relapse and reinfection: a second episode
      was considered a relapse if the fingerprint was identical or differed by only 1-4
      bands and was the first occurrence of that pattern in the population. Rates of
      and risk factors for recurrence, reinfection disease, and relapse were estimated
      using survival analysis and Poisson regression. RESULTS: Five hundred and eighty
      four culture-positive episodes of tuberculosis were diagnosed and treatment was
      completed during 1995-2003 in patients with known HIV status; 53 culture-positive
      recurrences occurred by May 2005. Paired fingerprints were available for 39 of
      these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in
      HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV
      negative individuals. Using multiple imputation to allow for missing fingerprint
      information, the rate of reinfection disease in HIV-positive individuals was
      2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years.
      CONCLUSIONS: HIV increases the rate of recurrent tuberculosis in this setting by
      increasing the rate of reinfection disease, not relapse.

PMID- 20042849
TI  - The high cost of second-line antiretroviral therapy for HIV/AIDS in South Africa.
AB  - OBJECTIVE: The present article estimates the cost and outcomes of second-line
      antiretroviral therapy. The cost of second-line drugs is generally higher than
      that of first-line drugs and it is expected that the absolute number of patients
      on second-line antiretroviral therapy will increase over time. This information
      is crucial for planning and budgeting. METHODS: Resource utilization and outcome
      data were extracted for patients who initiated standard second-line therapy.
      Resource usage was measured from second-line initiation for 12 months and
      outcomes were determined at 12 months. Unit costs were applied to resource usage
      using standard costing techniques. Costs were classified into drug, laboratory,
      visit, and fixed costs. Outcomes at 12 months were determined using attendance
      status, diagnostic results, and treatment status. Average cost per patient and
      average cost per outcome were reported. RESULTS: Of the 293 participants in the
      study cohort, 58% remained in care and responding, 15% were in care but not
      responding, and 26% were no longer in care. During the 12 months following second
      line initiation, the average cost per participant was $1037. Most of the cost per
      patient was attributable to drugs (71%), 13% to laboratory tests, 10% to clinic
      and pharmacy visits, and 6% to infrastructure and other fixed costs. Second-line
      therapy was 2.4 times more expensive per year in care than first-line therapy.
      CONCLUSION: The gradual increase in second-line numbers that can be expected as
      treatment programs mature may cause a meaningful increase in the overall average
      cost per patient treated.

PMID- 20042848
TI  - Male circumcision and risk of male-to-female HIV-1 transmission: a multinational
      prospective study in African HIV-1-serodiscordant couples.
AB  - OBJECTIVE: Male circumcision reduces female-to-male HIV-1 transmission risk by
      approximately 60%. Data assessing the effect of circumcision on male-to-female
      HIV-1 transmission are conflicting, with one observational study among HIV-1
      serodiscordant couples showing reduced transmission but a randomized trial
      suggesting no short-term benefit of circumcision. DESIGN/METHODS: Data collected
      as part of a prospective study among African HIV-1-serodiscordant couples were
      analyzed for the relationship between circumcision status of HIV-1-seropositive
      men and risk of HIV-1 acquisition among their female partners. Circumcision
      status was determined by physical examination. Cox proportional hazards analysis
      was used. RESULTS: A total of 1096 HIV-1-serodiscordant couples in which the male
      partner was HIV-1-infected were followed for a median of 18 months; 374 (34%)
      male partners were circumcised. Sixty-four female partners seroconverted to HIV-1
      (incidence 3.8 per 100 person-years). Circumcision of the male partner was
      associated with a nonstatistically significant approximately 40% lower risk of
      HIV-1 acquisition by the female partner (hazard ratio 0.62, 95% confidence
      interval 0.35-1.10, P = 0.10). The magnitude of this effect was similar when
      restricted to the subset of HIV-1 transmission events confirmed by viral
      sequencing to have occurred within the partnership (n = 50, hazard ratio 0.57, P
      = 0.11), after adjustment for male partner plasma HIV-1 concentrations (hazard
      ratio 0.60, P = 0.13), and when excluding follow-up time for male partners who
      initiated antiretroviral therapy (hazard ratio 0.53, P = 0.07). CONCLUSION: Among
      HIV-1-serodiscordant couples in which the HIV-1-seropositive partner was male, we
      observed no increased risk and potentially decreased risk from circumcision on
      male-to-female transmission of HIV-1.

PMID- 20042850
TI  - Postsplenectomy sclerosing extramedullary hematopoietic tumor with unexpected
      good clinical evolution: morphologic, immunohistochemical, and molecular analysis
      of one case and review of the literature.
AB  - Sclerosing extramedullary hematopoietic tumor has been described as a rare
      manifestation of chronic myeloproliferative neoplasm. The lack of knowledge about
      this entity has caused it to be mistaken for many types of nonhematopoietic and
      hematopoietic tumors. We present the case of a 71-year-old lady with a long
      history of primary myelofibrosis, which developed multiple abdominal sclerosing
      extramedullary hematopoietic tumors with good clinical evolution. Nonchronic
      myeloid leukemia myeloproliferative neoplasm included a JAK2 mutation as part of
      the diagnosis algorithm. Particularly, idiopathic myelofibrosis is related with a
      JAK2 mutation in 50% of the cases with a pejorative prognosis. The absence of
      JAK2 demonstrated in the paraffin samples of the tumors may be related to the
      unusual evolution in this particular case. Morphologically differential diagnoses
      considered in the evaluation of this entity and in our case included sarcomas
      mainly liposarcoma, anaplastic carcinoma, and Hodgkin lymphoma.

PMID- 20042851
TI  - Podoplanin expression in basal and myoepithelial cells: utility and potential
      pitfalls.
AB  - Podoplanin, D2-40, is often used for highlighting lymphatics. However, it has
      been described in a variety of normal and neoplastic tissues. We evaluated the
      expression of D2-40 in breast, salivary gland, skin, and mucosa, all organs rich
      in myoepithelial cells and basal cells. This study assessed the utility of using
      D2-40 to highlight basal/myoepithelial cells and to identify potential pitfalls
      in misinterpretation of lymphatic invasion. Our results showed that myoepithelial
      cells in breast and salivary gland and basal cells in prostate consistently
      demonstrate D2-40 immunoreactivity, but typically less intensely than lymphatics.
      Cutaneous and mucosal-based basal cells also have D2-40 expression, but often in
      a patchy, focal manner. In addition, many salivary gland tumors and squamous cell
      carcinomas had strong D2-40 expression, sometimes making distinction of
      lymphatics versus tumor edge staining difficult. D2-40 is excellent for assessing
      lymphatic invasion in breast, prostate, and cervix as long as the pathologist is
      aware of the expression in myoepithelial cells/basal cells to avoid
      misinterpretation of ductal carcinoma in situ or normal prostate glands or tumor
      stroma retraction as tumor lymphatic invasion. Given the patchy positivity in
      basal cells of skin and mucosa and the reactivity in squamous cell carcinoma, D2
      40 was not helpful in assessing for microinvasion of squamous cell carcinoma.

PMID- 20042852
TI  - Follicular variant of papillary carcinoma: reproducibility of histologic
      diagnosis and utility of HBME-1 immunohistochemistry and BRAF mutational analysis
      as diagnostic adjuncts.
AB  - CONTEXT: Despite the recognition of the follicular variant of papillary carcinoma
      of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic
      category has remained poor. Architectural features have been of variable utility
      as some FVPTC seem encapsulated, whereas others are multifocal and may be
      confused with nodular hyperplasia. Nuclear features are important for diagnosis
      of FVPTC, but some authors have discounted the utility of nuclear grooves and
      inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1)
      have been suggested as markers for FVPTC. OBJECTIVE: To investigate the frequency
      of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the
      diagnosis was established by 100% consensus among a panel of 6 surgical
      pathologists. DESIGN: Twenty-eight specimens with an original diagnosis of FVPTC
      and 10 cases with other diagnoses were obtained from the surgical pathology files
      of the University of Utah School of Medicine. All specimens were independently
      reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15
      mutations and HMBE-1 expression. RESULTS: Complete agreement among pathologists
      for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally
      diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases
      with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously
      diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME
      1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of
      FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of
      papillary carcinoma of the thyroid (classic or follicular variant). CONCLUSIONS:
      Interobserver agreement for the diagnosis of FVPTC is poor and testing for the
      BRAF mutation is only marginally helpful because a minority of FVPTCs possess the
      mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100%
      specificity but low sensitivity for the presence of papillary carcinoma of the
      thyroid including the follicular variant.

PMID- 20042853
TI  - Immunoglobulin light chain immunohistochemistry revisited, with emphasis on
      reactive follicular hyperplasia versus follicular lymphoma.
AB  - The identification of monotypic light chains is an important adjunct to the
      diagnosis of B-cell lymphoma, yet to reliably perform it on formalin-fixed
      paraffin sections is often difficult. We have evaluated a new set of monoclonal
      antibodies to kappa and lambda light chains that are reactive in paraffin
      sections. In reactive lymphoid tissues, polytypic staining was noted in greater
      than 95% of cases, with strong staining of plasma cells, moderate staining of the
      follicular dendritic cell network, and weak staining of mantle zone cells. Strong
      staining of the appropriate light chain was seen in each of the 7 cases of
      multiple myeloma. In a series of 58 cases of B-cell lymphoma, correlation between
      the results of immunohistochemistry and flow cytometry was obtained in 36 cases
      (62%), including 32 cases (21 kappa and 11 lambda) in which a single light chain
      was expressed. Monotypic staining was also seen in 6 additional cases (10%) in
      which flow cytometry was negative. Thirty of 46 cases (65%) of follicular
      lymphoma showed monotypic light chain expression, in contrast to 64 of 67 cases
      (95%) of reactive lymphoid hyperplasia, which showed polytypic light chain
      expression. These antibodies may provide an effective adjunct to the diagnosis of
      B-cell lymphoma in routine diagnostic work.

PMID- 20042854
TI  - Expression of thyroid transcription factor-1 in colorectal carcinoma.
AB  - Thyroid transcription factor-1 (TTF-1) is a member of the homeodomain
      transcription family expressed in epithelial cells of the thyroid and lung.
      Although nuclear TTF-1 is generally considered a specific marker for lung and
      thyroid neoplasms, it has been reported to be positive in other types of tumors
      including colorectal carcinoma (CRC). During metastatic adenocarcinoma workup for
      patients who had a history of CRC, we identified 4 positive TTF-1 cases using
      clone 8G7G3/1. Three of the 4 corresponding primary carcinomas were also positive
      for TTF-1. Therefore, we sought to retrospectively investigate the expression of
      TTF-1 in 100 CRC cases constructed in tissue microarray blocks and whole tissue
      sections of the 4 primary tumors corresponding to the 4 positive metastases. In
      tissue microarray cases, all cases had negative nuclear staining. Our results
      suggest that during immunohistochemical workup for adenocarcinoma, especially
      when the differential diagnosis includes the lung and CRC, TTF-1 results should
      be interpreted with caution as a small percentage of CRC expresses this marker.
      Positive nuclear TTF-1 in a metastatic carcinoma does not rule out CRC primary.
      Clinicopathologic correlation, tumor morphology, and a panel of
      immunohistochemical markers are essential to render the correct diagnosis.

PMID- 20042855
TI  - Ventilator management for hypoxemic respiratory failure attributable to H1N1
      novel swine origin influenza virus.
AB  - Novel H1N1 swine origin influenza virus has led to a worldwide pandemic. During
      the pandemic, a significant number of patients became critically ill primarily
      because of respiratory failure. Most of these patients required intubation and
      mechanical ventilation and were treated with conventional modes of mechanical
      ventilation using a lung-protective strategy with low tidal volumes, plateau
      pressures <30 to 35 cm H2O, and optimal positive end-expiratory pressure. In some
      patients with persistent hypoxemia, alternative modes of ventilation, such as
      high-frequency oscillatory ventilation and airway pressure release ventilation,
      were used. We review the ventilatory management, recruitment maneuvers, prone
      positioning, and goals of ventilatory therapy for hypoxemic respiratory failure
      in general, as well as lessons learned in the management of H1N1-related
      respiratory failure.

PMID- 20042856
TI  - Laboratory diagnosis of 2009 H1N1 influenza A virus.
AB  - The emergence of 2009 pandemic influenza H1N1 has necessarily led to the rapid
      evolution of sensitive, specific, and high-throughput molecular diagnostic assays
      for this virus at the same time that clinical laboratories attempt to cope with
      increasing demands in the setting of resource limitations. This situation has
      given rise to testing algorithms focusing on priority, clinical relevance, and
      appropriate surveillance. We describe the current state of understanding around
      diagnostic testing and laboratory detection of 2009 H1N1 influenza A virus.

PMID- 20042857
TI  - Defibrillation delivered during the upstroke phase of manual chest compression
      improves shock success.
AB  - OBJECTIVE: The current standard of manual chest compression during
      cardiopulmonary resuscitation requires pauses for rhythm analysis and shock
      delivery. However, interruptions of chest compression greatly decrease the
      likelihood of successful defibrillations, and significantly better outcomes are
      reported if this interruption is avoided. We therefore undertook a prospective
      randomized controlled animal study in an electrically induced ventricular
      fibrillation pig model to assess the effects of timing of defibrillation on the
      manual chest compression cycle on the defibrillation threshold. DESIGN:
      Prospective, randomized, controlled animal study. SETTING: University-affiliated
      research laboratory. SUBJECTS: Yorkshire-X domestic pigs (Sus scrofa).
      INTERVENTIONS: In eight domestic male pigs weighing between 24 and 31 kg,
      ventricular fibrillation was electrically induced and untreated for 10 secs.
      Manual chest compression was then performed and continued for 25 secs with the
      protection of an isolation blanket. The depth and frequency of chest compressions
      were guided by a cardiopulmonary resuscitation prompter. Animals were randomized
      to receive a biphasic electrical shock in five different compression phases with
      a predetermined energy setting. A control phase was chosen at a constant 2 secs
      after discontinued chest compression. A grouped up-down defibrillation threshold
      testing protocol was used to compare the success rate at different coupling
      phases. After a recovery interval of 4 mins, the sequence was repeated for a
      total of 60 test shocks for each animal. MEASUREMENTS AND MAIN RESULTS: No
      difference in coronary perfusion pressure before delivering of the shock was
      observed among the six study phases. The defibrillation success rate, however,
      was significantly higher when shocks were delivered in the upstroke phase of
      manual chest compression. CONCLUSION: Defibrillation efficacy is maximal when
      electrical shock is delivered during the upstroke phase of manual chest
      compression.

PMID- 20042858
TI  - Early prediction of Candida glabrata fungemia in nonneutropenic critically ill
      patients.
AB  - OBJECTIVE: Candida species represent the fourth cause of nosocomial bloodstream
      infections worldwide. Because Candida glabrata has become the second most
      frequently identified yeast and because the rate of fluconazole-resistant C.
      glabrata strains reaches 10% to 15%, initial antifungal therapy based on
      fluconazole in nonneutropenic hemodynamically stable patients, as recommended by
      current guidelines, may be an ineffective option. Our aim was to determine easy
      to-identify risk factors for C. glabrata fungemia likely to guide and improve
      initial antifungal therapy. DESIGN: Prospective multicenter cohort study.
      SETTING: Five French intensive care units. PATIENTS: Consecutive nonneutropenic
      patients without known Candida colonization who had blood culture-confirmed
      fungemia over a 4-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      A total of 8206 patients were screened. One hundred fifty-four patients with
      blood culture-confirmed fungemia constituted the cohort, of whom 48 had C.
      glabrata fungemia and 106 had nonglabrata fungemia. Patients' baseline
      characteristics and in-intensive care unit events potentially related to C.
      glabrata fungemia were systematically recorded. Compared with patients with
      nonglabrata fungemia, patients with C. glabrata fungemia were older and more
      severely ill, had received more antibiotics, and were more likely to have
      undergone surgery. The stepwise logistic regression analysis identified six
      independent risk factors for C. glabrata fungemia: age >60 yrs, recent abdominal
      surgery, interval from intensive care unit admission to first positive blood
      culture <or=7 days, recent use of cephalosporins, solid tumor, and absence of
      diabetes mellitus. The model showed satisfying goodness of fit (Hosmer-Lemeshow
      statistic = .26) and discrimination (c statistic = .89). CONCLUSIONS: We found
      six early available and easy-to-identify risk factors for C. glabrata fungemia.
      When these factors are present, alternatives to fluconazole for initial
      antifungal therapy should be considered.

PMID- 20042859
TI  - Genetics of cholestatic liver disease in 2010.
AB  - PURPOSE OF REVIEW: Many of the cholestatic diseases show similar clinical
      features, despite underlying differences in the genetic etiology. The present
      review aims to present recent insight into this etiological heterogeneity. RECENT
      FINDINGS: Mutations in the genes causing progressive familial intrahepatic
      cholestasis are also involved in less severe phenotypes like benign recurrent
      intrahepatic cholestasis, gallstone disease, intrahepatic cholestasis of
      pregnancy and drug-induced cholestasis. This probably represents a continuum of
      severity of the mutations involved, but also complex patterns of inheritance
      ranging from monogenic autosomal recessive disorders to heterozygosity only
      conferring a moderate increase in disease risk, where additional genetic or
      environmental factors are needed to acquire a disease phenotype. Recent genome
      wide association studies in the inflammatory cholestatic diseases primary biliary
      cirrhosis and primary sclerosing cholangitis have revealed susceptibility genes
      involved in autoimmunity and inflammatory bowel disease, whereas the genetic risk
      factors for the biliary preference of these diseases remain unknown. SUMMARY: The
      complexity of the genetic contribution to cholestatic liver disease needs to be
      accounted for to fully understand the pathogenesis of these conditions.

PMID- 20042860
TI  - Food addiction: true or false?
AB  - PURPOSE OF REVIEW: Food addiction has been implicated as a putative causal factor
      in chronic overeating, binge eating, and obesity. The concept of food addiction
      has been controversial historically due to definitional and conceptual
      difficulties and to a lack of rigorous scientific data. RECENT FINDINGS: Support
      for the food addiction hypothesis comes from alterations in neurochemistry
      (dopamine, endogenous opioids), neuroanatomy (limbic system), and self-medication
      behaviors. Foods identified as having potential addictive properties include
      sweets, carbohydrates, fats, sweet/fat combinations, and possibly processed
      and/or high salt foods. Eating topography has been identified as a necessary
      factor in neural pathway changes that promote addiction-like properties in
      response to some foods. A recently developed food addiction scale shows promise
      in identifying food addiction. SUMMARY: Recent findings have strengthened the
      case for food addiction. These findings may serve to validate the perception of
      food addiction in patients and inform psychoeducational, cognitive-behavioral,
      and/or pharmacological treatment for chronic food cravings, compulsive
      overeating, and binge eating that may represent a phenotype of obesity. Screening
      for food addiction has the potential to identify people with eating difficulties
      that seriously compromise weight management efforts. Future research should
      include a focus on human food addiction research; evaluating the impact of
      treatment on underlying neurochemistry; and prevention or reversal of food
      addiction in humans.

PMID- 20042862
TI  - Cardiac MRI reference values for athletes and nonathletes corrected for body
      surface area, training hours/week and sex.
AB  - OBJECTIVES: To establish cardiac MRI reference values for endurance athletes and
      nonathletes, and study the impact of variables related to ventricular volumes and
      wall-mass. METHODS: Three hundred and thirty-six prospectively recruited healthy
      individuals aged 18-39 years (mean age 26+/-6 years, 46% women) underwent cardiac
      MRI: 79 elite athletes (exercising >18 h/week), 143 regular athletes (9-18
      h/week), and 114 matched nonathletes (< or =3 h/week). RESULTS: Body surface area
      corrected right (RV) and left ventricular (LV) end-diastolic volume (EDV ml/m2)
      and wall mass (g/m2) were significantly higher (P<0.0005) in regular/elite
      athletes than in nonathletes (nonathlete/regular-athlete/elite-athlete; men RV
      EDV 111/136/144, RV-wall mass 12/14/15, LV-EDV 101/123/129, LV-wall mass
      48/62/69; women RV-EDV 96/115/118, RV-wall mass 10/13/14, LV-EDV 90/107/107, LV
      wall mass 34/46/50). Male sex, body surface area, and training hours/week
      increase ventricular volume and wall mass. In elite athletes, short-axis RV
      diameter exceeded 50 mm in 49/16% (men/women), and LV diameter exceeded 60 mm in
      55/16% (men/women). Interventricular septal-wall thickness was 13-15 mm in 5%
      regular and 15% elite male athletes. CONCLUSION: Cardiac MRI reference values
      show increased ventricular volumes, diameters, wall mass, and wall thickness for
      endurance athletes compared with nonathletes. High training hours/week and male
      sex result in an increased overlap with standard thresholds for cardiomyopathy.
      To help prevent inconclusive reports, the 95th percentile reference values can be
      used as an alternative to standard upper limits used for the general population.

PMID- 20042863
TI  - Dentists' perspectives on oral cancer: a survey in Northern Germany and a
      comparison with international data.
AB  - The objective of this study was to assess the knowledge on diagnostic procedures
      and risk factors for oral cancer among dentists in Northern Germany by means of a
      standardized questionnaire. A self-administered questionnaire was mailed to all
      dentists in Schleswig-Holstein, Germany, which was composed of 41 items focusing
      on knowledge about diagnostic procedures for oral cancer and its main risk
      factors. Three hundred and six of 2,233 questionnaires were returned and
      analysed. Most dentists correctly agreed that early detection of oral cancer
      improves 5-year survival. Knowledge of the facts that oral cancer is mostly
      diagnosed at an advanced stage and that the floor of the mouth is a common site
      to be affected was higher compared with international data. In contrast,
      knowledge was lower on the appearance of oral cancer and its symptoms in the
      early stages. Dentists were less certain about the role of nonrisk factors (e.g.
      family history) than that of risk factors. Continuous education on oral cancer
      within the past year was the only background factor that significantly
      contributed to a better knowledge onrisk-related and diagnostic factors. Profound
      knowledge about diagnostic procedures and risk factors for oral cancer is
      essential for dentists. This survey was informative with regard to areas of high
      versus low knowledge and will help design appropriate continuing education
      programmes.

PMID- 20042864
TI  - Serum cholesterol level, use of a cholesterol-lowering drug, and breast cancer:
      results from the prospective E3N cohort.
AB  - Metabolic syndrome, including low HDL cholesterol, has been associated with an
      increased breast cancer risk, whereas little is known of the relationship with
      total cholesterol. Cox proportional hazards regression models were performed to
      evaluate the association between self-reported total serum cholesterol,
      cholesterol-lowering drugs, and risk of breast cancer in 69 088 women from the
      French E3N cohort study. A total of 2932 cases of primary invasive breast cancer
      were reported during 12 years of follow-up. Compared with women with low/normal
      serum cholesterol (<6.6 mol/l), users of cholesterol-lowering drugs had a
      significantly decreased breast cancer risk [hazard ratio (HR): 0.79, 95%
      confidence interval (CI): 0.68, 0.93]. There was no variation in HRs according to
      the menopausal status. In strata defined by the hormone receptor status of the
      tumor, the risk reached statistical significance only for the estrogen-positive
      and progesterone-positive receptor subtype (HR: 0.64, 95% CI: 0.50, 0.82). A high
      cholesterol without cholesterol-lowering drug use was not associated with breast
      cancer risk (HR: 0.99, 95% CI: 0.85, 1.15) in the entire population. Our result
      concerning cholesterol-lowering drugs is consistent with studies showing that
      hypolipidemic molecules are effective in inhibiting cancer cell growth
      proliferation. Further studies should investigate whether these findings apply to
      all classes of cholesterol-lowering drugs.

PMID- 20042865
TI  - Wilson's disease: long-term follow-up of a cohort of 24 patients treated with D
      penicillamine.
AB  - BACKGROUND AND STUDY AIMS: Detailed data on long-term effectiveness of various
      drug therapies in Wilson's disease (WD) are lacking. Therefore, we
      retrospectively reviewed our patient cohort treated with D-penicillamine.
      PATIENTS AND METHODS: This study reports on the clinical presentation, the
      diagnostic evaluation, and the disease course in 24 WD patients treated long-term
      (15+/-12 years, between 1969 and 2009) with D-penicillamine. RESULTS: The overall
      survival in our cohort was 91.6%. Twenty-two of 24 patients had liver disease at
      presentation, 17 of 24 patients (71%) had cirrhosis, 11 of whom had complications
      of cirrhosis. Six of 11 of these patients showed hepatological improvement (five
      of six) or stabilization (one of six), three of 11 were transplanted, one of 11
      died, one of 11 discontinued follow-up. In the six of 17 cirrhotic patients
      without complications, improvement (four of six) or stabilization (two of six)
      occurred. Of all other patients (seven of 24), five of seven showed improvement
      (three of five) or stabilization (two of five), hepatological deterioration
      occurred only in one patient due to poor therapy compliance and one of seven
      discontinued follow-up. Neuropsychiatric symptoms were present in 13 of 24 at
      presentation and resolved in one of 13, decreased in seven of 13, stabilized in
      four of 13 and worsened in one of 13 patients (due to poor compliance). In
      general, we observed a favorable hepatological and neurological evolution with D
      penicillamine. CONCLUSION: Despite the presence of liver disease or
      neuropsychiatric symptoms at baseline in all but one of the patients, we report
      beneficial results on liver and neurological disease after very long-term
      treatment with D-penicillamine, thereby adding to its reputation as 'first-line'
      therapy in WD.

PMID- 20042866
TI  - Effect of transcutaneous electrical nerve stimulation on sensation thresholds in
      patients with painful diabetic neuropathy: an observational study.
AB  - Transcutaneous electrical nerve stimulation (TENS) is one of the therapies for
      painful neuropathy. Its analgesic mechanisms probably involve the gate control
      theory, the physiological block and the endogenous pain inhibitory system. The
      aim of the study was to determine whether TENS improves small fibre function
      diminished because of painful diabetic neuropathy. Forty-six patients with
      painful diabetic neuropathy were treated with TENS three consecutive hours a day
      for 3 weeks. Treatment effect was evaluated with cold, warm, cold pain and heat
      pain thresholds, vibration perception thresholds and touch perception thresholds.
      In all patients, thermal-specific and thermal pain sensitivity determination
      showed quantitative and qualitative abnormalities in all the measured spots.
      After the TENS therapy, no statistically significant changes in cold, warm, cold
      pain, heat pain, vibratory perception and touch perception thresholds were
      observed in the stimulated area. TENS did not alter C, Adelta nor Abeta fibre
      mediated perception thresholds. The observed changes at thenar are probably
      because of central mechanisms. In general, analgesic mechanisms of TENS are
      likely to be complex.

PMID- 20042867
TI  - Benefits and harms of sick leave: lack of randomized, controlled trials.
AB  - The aim of this study was to try to identify those randomized controlled trials
      that compare sick leave with no sick leave or a different duration or degree of
      sick leave. A comprehensive, systematic, electronic search of Clinical Evidence,
      the Cochrane Library and PubMed, and a manual search of the Campbell Library and
      a journal supplement was carried out. Only two studies with randomization of sick
      leave were found. Patients, who were suspected of having whiplash injuries
      following a car accident, were randomly assigned to either 14 days on sick leave
      wearing a neck collar, or no neck collar or sick leave, and employees with
      musculoskeletal disorders were randomized to part-time sick leave and work
      adjustments, or full-time sick leave. Over 99% of the studies on sick leave were
      observational. The reason for the scarcity of randomized controlled trials is
      unknown. There is a definite, urgent need for randomized, controlled studies of
      the effects that sick leave has on health issues.

PMID- 20042868
TI  - Undiagnosed HIV infection among New York City jail entrants, 2006: results of a
      blinded serosurvey.
AB  - OBJECTIVE: Since 2004, when all New York City jail entrants began being offered
      rapid testing at medical intake, HIV testing has increased 4-fold. To guide
      further service improvement, we determined HIV prevalence among jail entrants,
      including proportion undiagnosed. METHODS: Remnant serum from routine syphilis
      screening was salvaged for blinded HIV testing in 2006. Using HIV surveillance
      data and electronic clinical data, we ascertained previously diagnosed HIV
      infections before permanently removing identifiers. We defined "undiagnosed" as
      HIV-infected entrants who were unreported to surveillance and denied HIV
      infection. RESULTS: Among the 6411 jail entrants tested (68.9% of admissions),
      HIV prevalence was 5.2% overall (males 4.7%; females: 9.8%). Adjusting for those
      not in the serosurvey, estimated seroprevalence is 8.7% overall (6.5% males, 14%
      females). Overall, 28.1% of HIV infections identified in the serosurvey were
      undiagnosed at jail entry; only 11.5% of these were diagnosed during routine jail
      testing. Few (11.1%) of the undiagnosed inmates reported injection drug use or
      being men who have sex with men. CONCLUSIONS: About 5%-9% of New York City jail
      entrants are HIV infected. Of the infected, 28% are undiagnosed; most of whom
      denied recognized HIV risk factors. To increase inmate's acceptance of routine
      testing, we are working to eliminate the required separate written consent for
      HIV testing to allow implementation of the Centers for Disease Control and
      Prevention-recommended opt out testing model.

PMID- 20042869
TI  - Biography of James L. Achord, MD, MACP, MACG, FASGE.

PMID- 20042871
TI  - Endoscopy in the elderly: a review of the efficacy and safety of colonoscopy,
      esophagogastroduodenoscopy, and endoscopic retrograde cholangiopancreatography.
AB  - Gastrointestinal endoscopy including colonoscopy, esophagogastroduodenoscopy, and
      endoscopic retrograde cholangiopancreatography (ERCP) are safe and efficacious in
      elderly patients. Screening colonoscopies have little efficacy in patients over
      80 years. Colonoscopies performed for bleeding or iron-deficiency anemia have a
      higher yield in elderly patients. Colonic preparations were well tolerated and
      colonoscopic success rates are high in elderly patients. However, poor colonic
      preparation is more likely in these patients. Esophagogastroduodenoscopy is a
      high-yield procedure with no significant increase in adverse events in patients
      over 80 years with symptoms including dyspepsia and dysphagia. ERCP in the
      elderly carries a high degree of success with low complication rates. Elderly
      patients undergoing ERCP carry similar risks of bleeding and perforation and a
      lower risk of pancreatitis compared with younger patients. Advanced age should
      not be regarded as an absolute contraindication to any gastrointestinal endoscopy
      procedure.

PMID- 20042873
TI  - Anal skin tags: an overlooked indicator of Crohn's disease.

PMID- 20042872
TI  - Deamidated gliadin peptide antibodies as a routine test for celiac disease: a
      prospective analysis.
AB  - GOALS: This study was designed to establish whether deamidated gliadin peptide
      antibodies (DGP-AGA) could improve the serologic workup for celiac disease (CD).
      BACKGROUND: The best serologic approach for CD screening is currently based on
      the combined detection of tissue transglutaminase (tTGA), endomysial (EmA), and
      gliadin antibodies (AGA). STUDY: One hundred forty-four consecutive patients with
      gastrointestinal and extraintestinal signs suggestive for CD were investigated
      using serologic tests, that is, IgG and IgA DGP-AGA, IgA tTGA, IgA EmA, and
      duodenal biopsy. RESULTS: Forty-eight out of 144 patients (33%) had CD with
      different severity of villous atrophy. IgA tTGA showed 93.7% sensitivity compared
      with 91.6% for IgA EmA, 84.3% for IgA DGP-AGA, and 82.3% for IgG DGP-AGA. Of the
      3 cases negative for IgA tTGA, IgA EmA, and IgA DGP-AGA, 2 had total IgA
      deficiency, although both were positive for IgG DGP-AGA. IgG DGP-AGA showed a
      very high specificity for CD (98.9%), not only superior to IgA DGP-AGA (79.8%),
      but also to IgA tTGA (96.6%) and very close to IgA EmA (100%). CONCLUSIONS: Our
      prospective study shows that the combined search for IgA tTGA and IgG DGP-AGA
      provides the best diagnostic accuracy for CD, allowing the identification of all
      CD cases---except one---with a very high specificity. The serologic workup for CD
      screening could be significantly improved by the routine introduction of IgG DGP
      AGA together with IgA tTGA, thus reducing the number of tests and with an obvious
      advantage in terms of cost-efficacy.

PMID- 20042874
TI  - Lack of association between insulin-like growth factor-1 or insulin-like growth
      factor-binding protein-3 and left ventricular hypertrophy: results of the Study
      of Health in Pomerania.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is a major cardiac sequel of
      hypertension and a powerful predictor of cardiovascular morbidity and mortality.
      Several nonpopulation-based studies explored the association between insulin-like
      growth factor-1 (IGF-I) and LVH with conflicting results. The aim of the present
      study was to investigate the association of serum IGF-I or IGF-binding protein-3
      (IGFBP-3) levels with LVH in a population-based study. METHODS: From the cross
      sectional Study of Health in Pomerania, 1865 participants aged 45-79 years were
      included. Echocardiography was performed and left ventricular mass index
      calculated. LVH was defined as left ventricular mass index more than 48 g/m for
      men and more than 44 g/m for women. Serum IGF-I and IGFBP-3 levels were
      determined by chemiluminescence immunoassays. Analysis of variance and logistic
      regression were performed. RESULTS: LVH was present in 52.0% of the women and
      50.8% of the men. Our data did not obtain any significant association between
      serum IGF-I levels and left ventricular mass index or LVH in both men and women.
      Regarding IGFBP-3, women with low IGFBP-3 levels had an almost two-fold higher
      odds of LVH [odds ratio 1.76 (95% confidence limit 1.04-2.95)] compared with
      women with moderate IGFBP-3 levels. No such relation became apparent in men.
      CONCLUSION: No association between IGF-I levels and LVH was found. Potential
      hypertrophic effects of free serum IGF-I levels might be mediated by lower IGFBP
      3 levels.

PMID- 20042875
TI  - Trajectories of overweight and body mass index in adulthood and blood pressure at
      age 53: the 1946 British birth cohort study.
AB  - OBJECTIVE: To assess the relationship between patterns of overweight during
      adulthood and systolic (SBP) and diastolic (DBP) blood pressure (BP) at age 53.
      METHOD: Data are from 3035 male and female participants of the 1946 British birth
      cohort study. Body mass index (BMI) was obtained at ages 20, 26, 36, 43 and 53
      years. Censored regression models accounting for medication were used to
      investigate associations of BP at 53 years with overweight (BMI > 25 kg/m) at
      each age, age at first overweight and conditional weight gain. Sex interactions
      were also examined. RESULTS: Overweight at all ages except for 20 years in men
      was positively associated with BP at 53 years. After adjusting for current BMI,
      only overweight at age 43 contained additional information on BP in men. Men who
      were overweight at age 26 had a SBP 8.7 mmHg higher [95% confidence interval (CI)
      4.4-13.0] than those first overweight at 53 years. Similar patterns but smaller
      associations were seen in women [P(interaction) < 0.001). All periods of adult
      weight gain (26-36, 36-43, 43-53 years) were associated with a higher BP. BMI
      tracked strongly through adulthood, the BMI at 53 years in men first overweight
      at 26 was 30.9 kg/m (95% CI 30.5-31.4) compared to 26.4 (95% CI 26.3-26.6) in
      those first overweight at age 53. CONCLUSIONS: Early adult overweight and all
      periods of adult weight gain irrespective of earlier BMI were associated with
      higher BPs. This highlights the importance for later health of preventing
      overweight in early adulthood.

PMID- 20042876
TI  - Variability of mercury in urine among Mexican women residing in a mining area.
AB  - OBJECTIVE: To know the variability of the creatinine-adjusted inorganic mercury
      (HgUCr) levels in women aged >or=12 years to evaluate the impact of residing at a
      site contaminated by mercury in soil. METHODS: A cross-sectional epidemiologic
      study was conducted, in which 122 women participated, in whom, HgUCr was
      determined. Simultaneously, a questionnaire was applied for evaluate the
      different factors of mercury exposure, sociodemographic characteristics, and
      dietary hygiene measures. The environmental exposures were evaluated by measure
      Hg in soil and mining dumps. RESULTS: Women aged >30 years residing in areas
      contaminated by Hg in soil (>625 ppb) had 212% more HgUCr than the women who
      living in areas least contaminated, while women with amalgam dental fillings had
      120% more HgUCr than women without these. CONCLUSION: In conclusion, exposure to
      different physicochemical forms of Hg by environmental mechanisms and factors
      intrinsic to the women are probably responsible for HgUCr-level variability in
      the women.

PMID- 20042877
TI  - Mortality patterns and trends among 49,705 U.S.-based women in a petroleum
      company: update 1979-2000.
AB  - OBJECTIVE: To examine mortality patterns and trends in a cohort of women employed
      in U.S. operating segments of a petroleum company. METHODS: Based on human
      resources databases, we defined a cohort of 49,705 U.S.-based women with at least
      one day of company employment during 1979 to 2000. These data sources provided
      demographic and most work history information. Standardized mortality ratios and
      95% confidence intervals were calculated for 95 causes of death for the total
      cohort and with separate analyses by job type and operating segment when numbers
      allowed. RESULTS: Cohort women have a 25% lower overall death rate than the
      general U.S. female population comparison. This lower rate is expected in light
      of the "healthy worker effect" that influences employee studies. Circulatory
      diseases have a deficit of 40%, and external causes of death and cancer have
      deficits of 13% and 9%, respectively. For analyses by job type, office/clerical
      workers have an elevation in ovarian cancer (standardized mortality ratio = 1.40,
      95% confidence interval = 1.02 to 1.87), based on 46 deaths, with no work-related
      patterns. White-collar groups have generally large overall deficits for noncancer
      causes of death. In contrast, and based on smaller numbers, operators and
      laborers have elevations of motor vehicle accidents and other external causes of
      death, and laborers also have elevations of cerebrovascular disease and chronic
      obstructive pulmonary disease. These variations by job type are probably
      associated with differences in lifestyle factors. CONCLUSIONS: This large
      mortality surveillance study of women in the petroleum industry provides an
      opportunity for meaningful analysis of many causes of death. The study found an
      overall favorable mortality profile and, for a small number of elevations, helped
      identify possible subgroups for health and safety prevention programs and
      interventions.

PMID- 20042878
TI  - Do fear-avoidance beliefs play a role on the association between low back pain
      and sickness absence? A prospective cohort study among female health care
      workers.
AB  - Health care workers have a high prevalence of sickness absence because of low
      back pain (LBP). This study examined whether fear-avoidance beliefs (FAB): 1)
      predicted sickness absence and 2) moderated the association between LBP and
      sickness absence among 1724 newly educated health care workers with LBP >or= day
      during the previous 12 months. High FAB was associated with sickness absence days
      1 year later (relative risk, 1.45, 95% confidence interval = 1.24 to 1.70),
      controlled for LBP, previous sickness absence, and age. When controlling for work
      environmental factors, the association remained significant but decreased.
      Furthermore, the results showed that health care workers with high degree of LBP
      would have more sickness absence days if they also had high FAB. To reduce
      sickness absence, education about pain management must be presumed to be
      beneficial.

PMID- 20042879
TI  - The impact of cost intensive physicians on workers' compensation.
AB  - OBJECTIVE: To identify physicians linked to high-cost workers' compensation
      claims. METHODS: Contrast the cost and duration of claims associated with cost
      intensive physicians (CIPs) and other physicians (OPs) on 5 years of closed
      claims paid by the Louisiana Workers' Compensation Corporation. RESULTS:
      Identified 77 CIPs of 2034 physicians who treated Louisiana Workers' Compensation
      Corporation claimants. CIPs made up 3.8% of physicians but accounted for 72% of
      costs. CIP's treated 16 times more claimants, and their average claim cost was
      four times higher than the OPs ($46,239 vs $11,390, P < 0.01). CIP claims settled
      in 697 versus 278 days for OPs. Adjusted for age, sex, marital status,
      International Classification of Diseases, 9th revision group, and initial
      reserve, the odds ratio of CIP claims with a final cost of >$50,000 was 5.4.
      CONCLUSION: A small group of physicians (<4%) have a profound effect on overall
      workers' compensation costs.

PMID- 20042880
TI  - The cost of poor sleep: workplace productivity loss and associated costs.
AB  - OBJECTIVE: To assess the impact of sleep disturbances on work
      performance/productivity. METHODS: Employees (N = 4188) at four US corporations
      were surveyed about sleep patterns and completed the Work Limitations
      Questionnaire. Respondents were classified into four categories: insomnia,
      insufficient sleep syndrome, at-risk, and good sleep. Employer costs related to
      productivity changes were estimated through the Work Limitations Questionnaire.
      Performance/productivity, safety, and treatment measures were compared using a
      one-way analysis of variance model. RESULTS: Compared with at-risk and good-sleep
      groups, insomnia and insufficient sleep syndrome groups had significantly worse
      productivity, performance, and safety outcomes. The insomnia group had the
      highest rate of sleep medication use. The other groups were more likely to use
      nonmedication treatments. Fatigue-related productivity losses were estimated to
      cost $1967/employee annually. CONCLUSIONS: Sleep disturbances contribute to
      decreased employee productivity at a high cost to employers.

PMID- 20042881
TI  - Toward a climate for work resumption: the nonmedical determinants of return to
      work.
AB  - OBJECTIVE: People who have been on long-term absence from work because of ill
      health usually have reduced chances to resume work again. Nevertheless, little is
      known about its causal factors. The aim of this study is to present and test an
      empirical model to predict return to work of employees who are long-term absent
      for physical- or mental ill health reasons. METHOD: A longitudinal study has been
      performed with a sample of long-term absents in five European countries (N =
      1460). RESULTS: Health improvement is necessary but it alone not sufficient as
      precondition for return to work. Psychological factors (ie, self-efficacy,
      depression) and organizational factors have the highest impact. CONCLUSIONS: A
      climate for work resumption and its implications for personnel management
      practices to reduce/prevent workers to remain in absence leave when the medical
      symptoms have disappeared are discussed.

PMID- 20042882
TI  - A health hazard evaluation of antimony exposure in fire fighters.
AB  - OBJECTIVES: Some firefighter station uniforms contain the flame-retardant,
      antimony trioxide. National Institute for Occupational Safety and Health
      investigated a possible outbreak of antimony toxicity wherein 30 firefighters
      reported elevated antimony levels on hair analyses. METHODS: We surveyed and
      collected urine samples from firefighters not wearing (Fire Department A) and
      wearing (Fire Department B) antimony-containing pants. Urine antimony
      concentrations were measured and adjusted for creatinine. RESULTS: All 20
      participating firefighters from Fire Department A and 41 (97.6%) of 42
      participating firefighters from Fire Department B had urine antimony
      concentrations below or within the national reference range. No differences in
      urine antimony levels between departments were detected. CONCLUSIONS: Wearing
      antimony-containing uniforms does not pose a risk for antimony toxicity. This
      investigation highlights the importance of using validated methods for toxicity
      determination and of accurate, timely risk communication.

PMID- 20042883
TI  - A hospital-based case-control study of non-Hodgkin lymphoid neoplasms in
      Shanghai: analysis of personal characteristics, lifestyle, and environmental risk
      factors by subtypes of the WHO classification.
AB  - OBJECTIVES: To investigate potential risk factors (personal characteristics,
      lifestyle, and environmental factors) of non-Hodgkin lymphoid neoplasms (NHLN),
      including lymphomas and lymphocytic leukemia, according to the World Health
      Organization classification. MATERIALS AND METHODS: The investigation was a
      hospital-based case-control study consisting of 649 confirmed NHLN cases and 1298
      individually gender-age-matched patient controls at 25 hospitals in Shanghai. A
      17-page questionnaire was used to obtain information on demographics, medical
      history, family history, lifestyle risk factors, employment history, residential
      history, and occupational and non-occupational exposures. Risk estimates were
      calculated using conditional logistic regression models. RESULTS: Potential risk
      factors of NHLN (all subtypes combined) or individual subtypes included low-level
      education, home or workplace renovation, living on a farm, planting crops, and
      raising livestock or animals. Some risk factors applied to all or most subtypes
      (such as lowlevel education, living on a farm, and raising livestock or animals),
      whereas others did not (such as the use of traditional Chinese medicines, which
      was associated with a reduced risk). Blood transfusions, hair dyes, or living
      near high-voltage power lines were not associated with an increased risk.
      CONCLUSIONS: The study identified a number of risk factors for NHLN overall and
      specific subtypes. Some risk factors were subtype-specific. The difference in
      risk by subtype underscores the etiologic commonality and heterogeneity of NHLN
      subtypes.

PMID- 20042884
TI  - The association of social support at work and in private life with sleeping
      problems in the Finnish health 2000 study.
AB  - OBJECTIVE: To investigate the associations of social support at work and in
      private life with sleeping problems and use of sleep medication. METHODS: In the
      nationwide Health 2000 Study, with a cohort of 3430 employees, social support at
      work and in private life, and sleep-related issues were assessed with self
      assessment scales. Purchases of sleep medication over a 3-year period were
      collected from the nationwide pharmaceutical register of the Social Insurance
      Institution. RESULTS: Low social support from supervisor was associated with
      tiredness (odds ratio [OR] 1.68, 95% confidence interval [CI] = 1.26 to 2.23) and
      sleeping difficulties within the previous month (OR 1.74, 95% CI = 1.41 to 1.92).
      Low support from coworkers was associated with tiredness (OR 1.55, 95% CI = 1.41
      to 1.92), sleeping difficulties within the previous month (OR 1.77, 95% CI = 1.32
      to 2.36), and only among women, with short sleep duration (OR 2.06, 95% CI = 1.22
      to 3.47). Low private life support was associated with short sleep duration (OR
      1.49, 95% CI = 1.13 to 1.98) and among women, with sleeping difficulties (OR
      1.46, 95% CI = 1.08 to 1.33). CONCLUSIONS: Low social support, especially at
      work, is associated with sleeping-related problems.

PMID- 20042885
TI  - The economic impact of a disability prevention program.
AB  - We evaluated the effect of an employer- and clinic-based intervention on
      indemnity, medical, and workers compensation costs. The intervention was designed
      to improve communication and coordination of employer and physician efforts to
      help employees with work-related injuries to return-to-work. The research design
      was a quasi-experimental comparison of expenditures in treatment and control
      employers and clinics, controlling for differences in baseline expenditures and
      other characteristics of the subjects. We estimated that the employer and clinic
      interventions produced combined savings of $490 per employee per year (21% of
      total health expenditures). Ninety-four percent of savings came from reduced
      medical expenditure. Our findings suggest that relative modest efforts at
      coordinating appropriate medical care with employer accommodation that allow
      early reintegration of injured workers back into the workforce could result in
      substantial reductions of medical expenditures.

PMID- 20042886
TI  - Divergent influence of different type A dimensions on job strain and effort
      reward imbalance.
AB  - BACKGROUND: We examined whether different Type A behavior dimensions have
      divergent influence on work stress. METHODS: The sample comprised 752
      participants from the Cardiovascular Risk in Young Finns Study. Data were
      collected by questionnaires. Type A behavior was reported in subjects'
      adolescence and adulthood, and work stress was reported in adulthood. Work stress
      was measured according to Karasek's job demands-job control model and Siegrist's
      effort-reward imbalance (ERI). RESULTS: High leadership predicted lower job
      strain. High hard-driving predicted higher job strain. High leadership predicted
      lower ERI in 2001 and higher reward at work. High aggression, hard-driving, and
      eagerness-energy predicted ERI. CONCLUSIONS: Leadership predicted low work
      stress, whereas high hard-driving seemed to predispose the employee to work
      stress. The current findings add to the work stress literature by showing a
      divergent influence of different Type A dimensions on work stress.

PMID- 20042887
TI  - Job-related osteoarthritis of the knee, foot, hand, and cervical spine.
AB  - OBJECTIVES: To assess the influence of occupational exposures on risk of site
      specific radiographic osteoarthritis (OA) of the knee, hand, foot, and cervical
      spine. METHODS: Using a cross-sectional design, data collected from men and women
      aged 40 years and older participating in the Clearwater Osteoarthritis Study were
      analyzed (n = 3436). Subjects' occupational exposures were queried using the
      study intake form, including stair climbing, standing on a rigid surface,
      squatting, and jolting. Physical examinations including radiographs of the knee,
      hand, foot, and cervical spine were conducted. The Kellgren and Lawrence ordinal
      scale was used to determine evidence of radiographic OA. RESULTS: Both the
      unadjusted and adjusted odds ratios (ORs) for men and women indicated that age
      and body mass index were associated with OA. There were no other significant odds
      ratios for the cervical spine. Among men, there were significant associations
      with knee OA for stair climbing and jolting of the legs and with foot OA with
      stair climbing. Among women, there was a significant association between standing
      on a rigid surface and knee OA. For hand OA in women, there was a significant
      association for jolting of the hands. CONCLUSIONS: Although the association with
      stair climbing was found in other investigations for knee OA, it was also
      associated with foot OA in this study. In addition, the jolting feature was seen
      in only one other study for men (knees) and novel for women (hands).

PMID- 20042888
TI  - Snoring and obstructive sleep apnea among former World Trade Center rescue
      workers and volunteers.
AB  - BACKGROUND: Snoring is a common symptom among workers with adverse health effects
      from their World Trade Center (WTC) occupational exposures. Rhinitis and upper
      airway disease are highly prevalent among these workers. Rhinitis has been
      associated with snoring and, in some studies, with obstructive sleep apnea (OSA).
      We examined the association of WTC exposure and findings on nocturnal
      polysomnogram, as well as known predictors of OSA in this patient population.
      METHODS: One hundred participants with snoring underwent a polysomnogram to
      exclude OSA. Comorbidities had been previously evaluated and treated. The apnea
      hypopnea index (AHI) defined and categorized the severity of OSA. Age, sex, body
      mass index (BMI), and WTC exposure variables were examined in bivariate and
      multiple regression analyses. RESULTS: Our study sample had a similar prevalence
      of five major disease categories, as we previously reported. OSA was diagnosed in
      62% of the patients and was not associated with any of those disease categories.
      A trend toward increasing AHI with increasing WTC exposure duration failed to
      reach the statistical significance (P = 0.14) in multiple regression analysis. An
      elevated AHI was associated with BMI (P = 0.003) and male sex (P < 0.001).
      CONCLUSIONS: OSA was associated with BMI and male sex but not with occupational
      WTC exposure indicators in this patient population.

PMID- 20042889
TI  - Employment and work impact of chronic migraine and episodic migraine.
AB  - OBJECTIVE: To determine work impact of chronic migraine (CM) versus episodic
      migraine (EM). METHODS: Data were from the 2005 American Migraine Prevalence and
      Prevention study, a longitudinal population survey of more than 11,000
      migraineurs. Lost productive time (LPT) was measured as missed work hours plus
      reduced productivity hour equivalents. RESULTS: Those with CM were 19% less
      likely to be working for pay compared with migraineurs with <or=3 headache
      days/month. On average, those with CM lost 4.6 hours/wk from headache compared
      with 1.1 hours for those with <or=3 headache-days/month. Those with 10 to 14
      headache-days/month or with CM accounted for 9.1% of employed migraineurs, 20.8%
      of work-related LPT, and 35% of the overall lost work time when considering
      medical leave and unemployment. CONCLUSIONS: The work impact of CM and high
      frequency EM will be underestimated if employment status is not measured.

PMID- 20042890
TI  - Immunohistochemical analysis of the S100A1, S100B, CD44 and Bcl-2 antigens and
      the rate of cell proliferation assessed by Ki-67 antibody in benign and malignant
      melanocytic tumours.
AB  - Malignant melanomas usually have an unfavourable prognosis and poor response to
      chemotherapy. Deregulation of cell proliferation, programmed cell death and
      intercellular interactions are among several important mechanisms that might lead
      to malignant transformation of melanocytes and melanoma progression. The S100A1,
      S100B, Bcl-2 and CD44 antigens have all been described as being involved in
      different processes of melanoma progression. The expression of these antigens, as
      well as the rate of cell proliferation, was analyzed retrospectively in
      melanocytic tumours from 126 patients (32 males and 94 females, age ranging from
      11 to 91 years). The series included benign (45 intradermal, 27 compound and
      eight displastic naevi) and malignant (39 primary and 14 metastatic) melanocytic
      tumours. The proliferating rate assessed by Ki-67 staining was lower in naevi
      than in melanomas, with a correlation coefficient of r = 0814. There was no
      overlap for rate of proliferation between benign and malignant tumours. The
      expression of S100A1 was low in benign melanocytic tumours and increased in
      malignant melanomas (r = 0.61). In contrast, a higher percentage of S100B antigen
      positive cells were observed in benign melanocytic lesions than in melanomas
      (Pearson correlation coefficient, 0.627). In addition, positive immunostaining
      for S100B antigen in malignant melanomas corresponded with the areas with
      increased proliferating rate. The expression of Bcl-2 was lower in melanomas than
      in benign melanocytic tumours (r = -0.53). Bcl-2-negative areas within melanomas
      had an increased proliferating rate. The expression of CD44 showed a large
      variation both in benign and malignant melanocytic tumours. CD44 antigen
      expression was higher in melanomas with known metastases than in those without
      metastases, but this difference was not statistically significant.

PMID- 20042891
TI  - Mid-humeral sentinel lymph node dissection in patients with primary cutaneous
      malignant melanoma.
AB  - In rare cases, lymphatic drainage from the malignant melanomas in the upper
      extremity may follow an unpredictable pattern (outside the axillary nodes), and
      these aberrant sentinel nodes may represent the only site of regional lymph node
      metastases. The precise anatomical landmarks and technical aspects of surgical
      exploration of these aberrant sentinel lymph nodes are rarely described in the
      literature, including aberrant sentinel mid-humeral lymph nodes. This report
      describes a step-by-step dissection of the mid-humeral sentinel lymph nodes in
      two patients with a primary malignant melanoma in the upper extremity, identified
      by lymphatic mapping. Recognition of precise regional anatomy and following a
      special surgical technique makes the procedure safe and successful, thus avoiding
      local complications and allowing a prompt recovery.

PMID- 20042893
TI  - Premature menopause is associated with increased risk of cerebral infarction in
      Japanese women.
AB  - OBJECTIVE: : Few epidemiological studies have examined the relationship between
      age at menopause and stroke incidence, and none have done so in Japanese women.
      Here, we investigated the relationship between age at menopause and stroke
      incidence in a large group of Japanese women. METHODS: : The study participants
      were 4,790 postmenopausal women aged 36 to 89 years enrolled in the Jichi Medical
      School Cohort Study, a population-based prospective study. Baseline data were
      obtained by questionnaire and health checkups between April 1992 and July 1995 in
      12 rural areas in Japan. The incidence of all strokes and stroke subtypes was
      monitored. RESULTS: : Mean (SD) participant age was 61.0 (6.7) years, and mean
      (SD) age at menopause was 48.3 (4.8) years. A total of 185 strokes were observed
      during a mean follow-up of 10.8 years. On adjustment for age, systolic blood
      pressure, total cholesterol, body mass index, smoking habits, and alcohol
      drinking habits, hazard ratios (95% CIs) of stroke for women who underwent
      menopause before age 40 years, at 40 to 44 years, at 45 to 49 years, and at 55
      years or after relative to those who underwent menopause at age 50 to 54 years
      were 1.56 (0.78-3.12), 1.59 (1.00-2.51), 1.28 (0.92-1.78), and 0.83 (0.38-1.81),
      respectively. However, hazard ratios (95% CI) of cerebral infarction for women
      who underwent menopause before age 40 years, at 40 to 44 years, at 45 to 49
      years, and at 55 years or after relative to those who underwent menopause at age
      50 to 54 years were 2.57 (1.20-5.49), 1.49 (0.80-2.78), 1.06 (0.67-1.68), and
      1.08 (0.43-2.74), respectively. CONCLUSIONS: : Our data suggest that Japanese
      women who undergo menopause before age 40 years are at an increased risk of
      cerebral infarction. Premature menopause should be considered an indicator of the
      need for more aggressive medical intervention aimed at the prevention of cerebral
      infarction.

PMID- 20042892
TI  - Hot flashes and cardiac vagal control: a link to cardiovascular risk?
AB  - OBJECTIVE: The understanding of the physiology of hot flashes is incomplete. The
      autonomic nervous system has been hypothesized to play a role in hot flashes but
      has received limited empirical attention. Furthermore, emerging research has
      linked hot flashes to cardiovascular risk. Reduced high-frequency heart rate
      variability (HF-HRV), an index of vagal control of heart rate, has been
      associated with cardiovascular events. We hypothesized that decreases in HF-HRV
      would occur during hot flashes relative to periods before and after hot flashes.
      METHODS: Thirty perimenopausal and postmenopausal women aged 40 to 60 years
      reporting four or more hot flashes per day underwent laboratory hot flash
      provocation testing, with electrocardiogram and measurement of sternal skin
      conductance. Hot flashes were reported and identified from sternal skin
      conductance. HF-HRV was estimated using spectral analysis of the heart rate time
      series. The 5-minute interval during the hot flash period was compared with that
      during two nonflash periods before and after the hot flash via mixed-effects
      models. RESULTS: HRV was significantly decreased during hot flashes relative to
      periods before (b = 0.18, SE = 0.05; P = 0.0001) and after (b = 0.16, SE = 0.05;
      P = 0.002) physiologically measured hot flashes, controlling for age, race,
      education, task condition, menopause status, task, hypertension status, diabetes
      status, physical activity, body mass index, smoking, and anxiety. Findings were
      unchanged when considering self-reported hot flashes. CONCLUSIONS: Significant
      decreases in cardiac vagal control occurred during hot flashes, which may help
      shed light on the physiology of hot flashes. The autonomic nervous system may
      deserve greater attention in understanding the mechanisms linking hot flashes to
      cardiovascular risk.

PMID- 20042894
TI  - Impact of gender on left ventricle function in postmenopausal women and age
      matched men: analysis of echocardiographic parameters in healthy participants and
      patients with coronary artery disease.
AB  - OBJECTIVE: Our aim was to evaluate the impact of gender on the diastolic function
      of the left ventricle in healthy men and women and in patients with coronary
      artery disease (CAD) without systolic impairment. METHODS: We examined 67 healthy
      participants (34 men with a mean age of 51 +/- 13 y and ejection fraction [EF] of
      62% +/- 3% and 33 women with a mean age of 53 +/- 11 y and EF of 63% +/- 3%; P =
      NS) and 60 patients with CAD (36 men with a mean age of 57 +/- 10 y and EF of 59%
      +/- 3% and 24 women with a mean age of 59 +/- 10 y and EF of 60% +/- 3%), paired
      with regard to age, heart rate, and medical treatment by transthoracic
      echocardiography with the assessment of mitral and pulmonary vein flow
      parameters, propagation of mitral filling waves, and tissue Doppler variables of
      mitral annulus motion (MAM). The impact of gender was assessed separately for the
      healthy participants and the CAD group. RESULTS: In healthy participants, the
      velocity of mitral inflow early wave and the systolic velocity of the pulmonary
      vein flow were significantly higher in women than in men: 77 +/- 18 versus 65 +/-
      19 cm/second (P < 0.05) and 64 +/- 14 versus 57 +/- 11 cm/second (P < 0.05),
      respectively. On the other hand, velocities of MAM in the atrial and systolic
      phases were higher in men than in women: 13 +/- 2 versus 12 +/- 2 cm/second and
      11 +/- 2 versus 10 +/- 2 cm/second, respectively (P < 0.05). The opposite
      tendency was observed in the CAD group: the ratio of early mitral inflow velocity
      to atrial mitral inflow velocity was significantly higher in male patients (1.1
      +/- 0.5 vs 0.8 +/- 0.2; P = 0.007) and there was a trend toward faster early wave
      propagation in men (40 +/- 9 vs 36 +/- 8 cm/s; P = 0.08). CONCLUSIONS: Our data
      suggest more efficient early diastolic filling in postmenopausal women than in
      age-matched men in healthy participants but an opposite relationship in patients
      with CAD.

PMID- 20042896
TI  - A novel method for olfactory bulbectomy using photochemically induced lesion.
AB  - We present the photochemically induced olfactory bulbectomy (P-bulbectomy) as a
      novel method to ablate the olfactory bulb thus inducing an animal model of
      depression. The photosensitizer Rose Bengal was injected through the tail vein
      and then the cool halogen light illuminated the skull region overlying of the
      olfactory bulb for 10 min. Two weeks after surgery, P-bulbectomy had completely
      removed olfactory bulb uniformly in all animals. P-bulbectomy induced typical
      depression-related behaviors such as hyperactivity in the open field test and an
      enhancement of immobility time and in the forced swimming test. Depression
      related neurohistological phenomenon was also seen; reduction of choline
      acetyltransferase-positive cell numbers in the medial septum and a decline in
      cell proliferation in the dentate gyrus of hippocampus. This study shows that P
      bulbectomy may be a convenient and reproducible experimental method to produce an
      animal model of depression.

PMID- 20042897
TI  - Late phase of L-LTP elicited in isolated CA1 dendrites cannot be transferred by
      synaptic capture.
AB  - In the CA1 region of mouse hippocampal slices, a strong tetanic stimulation
      triggers a long-lasting long-term potentiation (L-LTP), which requires
      transcription for the development of its late phase. Nevertheless, we were able
      to elicit such an L-LTP in CA1 dendrites separated from their somas provided that
      we restricted our investigations to isolated dendrites where a very robust early
      LTP was triggered. This particular type of L-LTP, which relied on translation of
      preexisting messenger RNAs - as it was blocked by anisomycin - could not be
      captured by another pathway activated only by a weak tetanic stimulation. This
      suggests that the plasticity-related proteins resulting from translation of
      messenger RNAs in dendrites cannot pass from the synaptic site where they were
      synthesized to another one.

PMID- 20042895
TI  - History of hot flashes and aortic calcification among postmenopausal women.
AB  - OBJECTIVE: Menopausal hot flashes are considered largely a quality-of-life issue.
      However, emerging research also links hot flashes to cardiovascular risk. In some
      investigations, this risk is particularly apparent among women using hormone
      therapy. The aim of this study was to determine whether a longer history of
      reported hot flashes over the study period was associated with greater aortic and
      coronary artery calcification. Interactions with hormone therapy use were
      examined in an exploratory fashion. METHODS: Participants included 302 women
      participating in the Healthy Women Study, a longitudinal study of cardiovascular
      risk during perimenopause and postmenopause, which was initiated in 1983. Hot
      flashes (any/none) were assessed when women were 1, 2, 5, and 8 years
      postmenopausal. Electron beam tomography measures of coronary artery
      calcification and aortic calcification were completed in 1997-2004. Associations
      between the number of visits with report of hot flashes, divided by the number of
      visits attended, and aortic or coronary artery calcification (transformed) were
      examined in linear regression models. Interactions by hormone therapy use were
      evaluated. RESULTS: Among women using hormone therapy, a longer history of
      reported hot flashes was associated with increased aortic calcification,
      controlling for traditional cardiovascular risk factors (b = 2.87, SE = 1.21, P <
      0.05). There were no significant associations between history of hot flashes and
      coronary artery calcification. CONCLUSIONS: Among postmenopausal women using
      hormone therapy, a longer history of reported hot flashes measured prospectively
      was associated with increased aortic calcification, controlling for traditional
      cardiovascular risk factors. Hot flashes may signal adverse cardiovascular
      changes among certain postmenopausal women.

PMID- 20042898
TI  - Selective increase in motor excitability with intraactive (self) versus
      interactive touch.
AB  - Corticomotor facilitation was investigated using transcranial magnetic
      stimulation in healthy young adults when they actively stroked either their own
      left palm (intraactive) or the experimenter's palm (interactive touch) with their
      right index finger. We predicted, based on the sensory cancellation hypothesis,
      that corticomotor facilitation would be lower with intraactive touch. Motor
      evoked potential amplitude in the right first dorsal interosseous was affected by
      mode of touch, but not by sex. In contrast to our prediction, motor evoked
      potential facilitation was larger (mean 14%) during intraactive touch. The
      present results are in agreement with recent evidence suggesting that self-touch
      represents a unique class of sensorimotor experiences that are critical for the
      elaboration of internal body structure representation.

PMID- 20042899
TI  - Involvement of TRPA1 in ET-1-induced pain-like behavior in mice.
AB  - Transient receptor potential ankyrin subfamily member 1 (TRPA1) is a nonselective
      cation channel known as a noxious cold-activated ion channel. Recent findings
      implicated its involvement in acute and chronic cold nociception processes. Here,
      we investigated whether TRPA1 is involved in endothelin-1 (ET-1)-induced
      spontaneous pain-like behavior in C57BL/6J mice. We found that TRPA1 antagonists,
      HC-030031 and AP18, significantly reduced the pain-like behavior caused by ET-1.
      AP18 also significantly reduced the pain caused by cinnamaldehyde, an agonist of
      TRPA-1. However, AP18 did not alleviate the pain caused by capsaicin. The pain
      like behavior caused by ET-1 was inhibited by phospholipase C inhibitor, but not
      by protein kinase C inhibitor. Low dose of ET-1 could potentiate cinnamaldehyde
      induced nociception. Our results suggested that TRPA1 is involved in ET-1-induced
      spontaneous pain-like behavior in mice.

PMID- 20042900
TI  - Gray matter in amnestic mild cognitive impairment: voxel-based morphometry.
AB  - Multiple regression voxel-based morphometry analyses were used to examine the
      relationship between regional gray matter volumes and neurocognitive performance
      in 10 patients with amnestic mild cognitive impairment and 20 healthy age-matched
      controls. Cognitive functioning was assessed with seven standardized
      neuropsychological tests. Patients with amnestic mild cognitive impairment
      exhibited impaired cognitive performance (on the Mini Mental State Examination,
      tests of verbal fluency, verbal and spatial learning and memory, and visual-motor
      abilities) and reduced gray matter volume in the right temporal pole. Across all
      participants, better performance on several neuropsychological tests was
      associated with higher regional gray matter volumes. Voxel-based morphometry
      provides an operator-unbiased means to investigate volumetric differences, which
      may be related to impaired neuropsychological functioning.

PMID- 20042901
TI  - Magnetoencephalography discriminates modality-specific infraslow signals less
      than 0.1 Hz.
AB  - DC-magnetoencephalography (DC-MEG) technique has been refined and allows to
      record cortical activity in the infraslow frequency range less than 0.1 Hz
      noninvasively. Important questions however, remained, especially, how specific
      these infraslow activations can be recorded and whether different activations,
      for example, motor versus acoustic, can be separated. To clarify these questions,
      in the present DC-MEG study, cortical infraslow activity was investigated
      intraindividually in response to different activation modalities, that is, motor
      versus acoustic: in 13 individuals, 30-s periods of finger movement or listening
      to concert music, were interleaved for 60 min. DC-MEG was capable to resolve
      intermodal differences concerning the relative amplitudes, field patterns, and
      source localizations. These results clarify that DC-MEG allows to identify and to
      discriminate modality-specific infraslow cortical neuronal signals.

PMID- 20042902
TI  - Auditory development in the absence of hearing in infancy.
AB  - The auditory brainstem pathways require stimulation to mature, but do they
      develop in the absence of auditory input? To answer this, peaks of the
      electrically evoked auditory nerve (wave eN1) and brainstem response (eII, eIII,
      and eV) were measured in 117 children with early-onset deafness who had received
      cochlear implants. Data were collected at cochlear implant activation. In the
      absence of significant input, the interpeak latency eN1-eIII decreased over the
      first year of life but remained constant thereafter. Chronic cochlear implant
      stimulation was required to promote significant reduction in eIII-eV interpeak
      latency. Thus, activity-independent changes occurring in infancy are concentrated
      in the caudal auditory brainstem and likely involve the auditory nerve. Changes
      requiring input are most prevalent in rostral brainstem.

PMID- 20042903
TI  - Telemedicine-assisted neurotology in post-Katrina Southeast Louisiana.
AB  - OBJECTIVE: This study evaluates technical requirements, privacy and legal
      constraints, reimbursement considerations, and overall feasibility of a new
      telemedicine neurotologic patient care delivery model in post-Katrina, Southeast
      Louisiana. METHODS: This study is a retrospective review of the first year of a
      telemedicine neurotology practice with limited on-site neurotology physician
      availability (3-days monthly) with a full-time on-site audiologist, a full-time
      specialty-trained nurse practitioner, full-time neurosurgery on-site
      availability, and full-time otolaryngology on-site availability. RESULTS: A
      combined "store-and-forward" and "real-time" telemedicine delivery model was
      implemented for a new neurotology practice. Technical requirements include secure
      data transfer, real-time video-streaming, high-quality video otoscopy and
      microscopy, infrared video eye movement visualization and recording, remote
      visualization of radiologic imaging studies, and formalized diagnostic algorithms
      for patient evaluation. Telemedicine patient evaluations occur with the patient
      in Baton Rouge, LA, while the examining neurotologist is linked through a secure,
      commercially available communication connection in Pittsburgh, PA. Specifically
      designed consent forms and bilocation licensing and liability insurance coverage
      were required. Third-party payers were consulted before implementation to assure
      adherence to local reimbursement requirements. During the first 12 months of
      operation, 450 patient encounters were accomplished purely through telemedicine,
      with an additional 800 on-site patient visits and 150 operative procedures,
      including 24 neurotologic skull base procedures. CONCLUSION: Telemedicine is a
      viable delivery model for neurotology care delivery. Planning and implementation
      of such a model requires systematic considerations of medical, nursing,
      information systems, legal, reimbursement, and management parameters. Although
      the authors' initial motivation for this model was the resource-restricted, post
      Katrina health care environment in South Louisiana, this delivery model has wider
      applicability in otolaryngology, other medical specialties, humanitarian
      outreach, and medical education. Prospective assessment of clinical outcomes and
      patient satisfaction is ongoing for objective validation of this delivery model.

PMID- 20042904
TI  - Third window vibroplasty: an alternative in surgical treatment of
      tympanosclerotic obliteration of the oval and round window niche.
AB  - OBJECTIVE: To describe a new technique in surgical treatment of obliterative
      tympanosclerosis by applying a floating mass transducer (FMT) to a third window.
      PATIENT: A 64-year-old woman with a severe combined hearing loss due to
      tympanosclerosis received a third window vibroplasty. INTERVENTION: A
      mastoidectomy and a posterior tympanotomy via the large facial recess were
      performed. The promontory was exposed by a transcanal approach. The third window
      was performed anterior inferior to the round window. The membranous cochlea was
      left intact. The FMT was gently pushed into the perichondrium-coated cochlear
      window. All other surgical steps were the same as in conventional FMT
      application. RESULTS: Preliminary data of this report reveal that vibroplasty
      with coupling of the FMT directly to a third window leads to similar audiological
      results compared with the conventional coupling of the FMT on the round window
      niche. CONCLUSION: The presented case demonstrates the applicability of a third
      window vibroplasty in obliterative tympanosclerosis. Further studies will show if
      our assumption of a reduced risk for inner ear trauma is justified or not.

PMID- 20042905
TI  - Less than 1% cerebrospinal fluid leakage in 1,803 translabyrinthine vestibular
      schwannoma surgery cases.
AB  - OBJECTIVE: To determine the incidence rate of cerebrospinal fluid (CSF) leak
      after translabyrinthine vestibular schwannoma surgery since the alteration of the
      surgical procedure. To compare with previous series and other series in
      literature. STUDY DESIGN: Database analysis. SETTING: Tertiary referral
      neurotologic private practice. PATIENTS: A series of 1,803 patients who underwent
      translabyrinthine vestibular schwannoma surgery between 1993 and 2009. The result
      of this group was compared with corresponding series. INTERVENTION:
      Translabyrinthine and extended translabyrinthine vestibular schwannoma surgery.
      Literature review and comparison. MAIN OUTCOME MEASURES: Rates of CSF leak in
      this series and historical perspective of the outcome. RESULTS: Fifteen patients
      (0.8%) of 1,803 cases had CSF leaks. The method used since 1993 has shown a
      significant improvement compared with major case series of the last 10 years.
      CONCLUSION: The methods used in translabyrinthine vestibular schwannoma surgery
      in our center can reduce CSF leakage to an absolute minimum. Compared with all
      large series, this could be a new era of translabyrinthine vestibular schwannoma
      surgery.

PMID- 20042906
TI  - Intractable benign paroxysmal positioning vertigo: long-term follow-up and inner
      ear abnormality detected by three-dimensional magnetic resonance imaging.
AB  - OBJECTIVE: To investigate the occurrence rate, prognosis, and inner ear
      abnormality in intractable benign paroxysmal positioning vertigo (BPPV). STUDY
      DESIGN: A prospective study. SETTING: Tertiary referral university hospital.
      PATIENTS: Intractable BPPV was defined in case of either a persistent nystagmus
      or a frequent relapse each lasting more than 1 year after the initial diagnosis.
      INTERVENTION: T2-weighted 3-dimensional fast imaging employing steady-state
      acquisition sequences of magnetic resonance imaging (MRI) were reconstructed 3
      dimensionally for 13 intractable BPPV patients and 14 control volunteers. MAIN
      OUTCOME MEASURE: Transition and relapse of nystagmus were monitored. Semicircular
      canals were evaluated for a stenosis or filling defect (obturation). RESULTS:
      Eighteen patients (4 with posterior canal type, 2 with horizontal canal type with
      geotropic nystagmus, and 12 with apogeotropic nystagmus) fulfilled the above
      criteria for intractability among 495 BPPV patients. The occurrence rate of
      intractable BPPV was 3.6%. Also, the rate of nystagmus transition was
      significantly higher in patients with geotropic nystagmus and the posterior canal
      type (100%) compared with those with apogeotropic nystagmus (33.3%). Of the 13
      intractable BPPV patients who underwent MRI, 11 (84.6%) had a total of 23 canals
      with abnormal appearance (29.5%), showing a significantly higher incidence
      compared with controls. There was no correlation between the affected canal
      diagnosed by MRI and the type of nystagmus. CONCLUSION: The low incidence of
      nystagmus transition in patients with apogeotropic nystagmus suggests a
      difference in pathophysiology between apogeotropic nystagmus and other types of
      BPPV. Stenosis and filling defect (obturation) of canals on MRI, which would
      indicate an innate narrowing and/or an otoconial jam of the semicircular canal,
      may account for the intractability of BPPV.

PMID- 20042907
TI  - Active middle ear implant compared with open-fit hearing aid in sloping high
      frequency sensorineural hearing loss.
AB  - OBJECTIVE: To compare 2 open-ear hearing solutions for sloping high-frequency
      sensorineural hearing loss: open-fit hearing aid (HA) and active middle ear
      implant (AMEI). STUDY DESIGN: Within-subjects prospective design. SETTING:
      Tertiary referral hospital. PATIENTS AND DEVICES: Fourteen patients with sloping,
      high-frequency sensorineural hearing loss were recruited from 39 patients
      previously implanted with an AMEI and 10 agreed to participate, ranging in age
      from 44 to 73 years (mean, 59 yr). Patients were selected because their hearing
      thresholds (500-3,000 Hz) qualified them for both AMEI and open-fit HA use. All
      patients received a Vibrant Soundbridge (Vibrant MED-EL) for an average of 25.1
      months before data collection and used their AMEI on a daily basis. The open-fit
      HA used in this study was the Delta 8000 (Oticon). Both study devices have been
      fit with the specific fitting strategies as recommended by the manufacturer. MAIN
      OUTCOME MEASURES: Sound-field hearing thresholds, Freiburger monosyllabic words
      in quiet, speech reception thresholds for 50% correct recognition for Freiburger
      numbers and for Oldenburg sentences in quiet, and speech reception thresholds for
      50% correct recognition for Oldenburg sentences in noise. RESULTS: Both HA and
      AMEI conditions showed significantly better sound-field thresholds and speech
      recognition on monosyllabic word and sentence tests in quiet and in noise than in
      the unaided condition. A comparison of aided conditions revealed that, in the
      AMEI-aided condition, high-frequency audibility and speech discrimination scores
      in quiet and in noise were significantly better than those in the open-fit HA.
      CONCLUSION: Both open-fit HAs and AMEIs provided audiologic benefit to patients
      with sloping high-frequency sensorineural hearing loss. However, despite
      overlapping indication criteria for the 2 devices, performance with the AMEI was
      significantly better for the AMEI than for the open-fit HA.

PMID- 20042908
TI  - Ceruminous adenocarcinoma.

PMID- 20042909
TI  - Pandemic influenza and pediatric intensive care.
AB  - OBJECTIVE: To assess the adequacy of preparedness planning for an influenza
      pandemic by modeling the pediatric surge capacity of healthcare facility and
      pediatric intensive care unit (PICU) requirements over time. Governments and
      Public Health authorities have planned preparedness activities and training for a
      flu pandemic. PICU facilities will be the limiting factor in healthcare provision
      for children but detailed analyses for needs and demands in PICU care have not
      been published. DESIGN: Based on the Center for Disease Control and Prevention
      and World Health Organization estimates and published models of the expected
      evolution of pandemic flu, we modeled the pediatric surge capacity of healthcare
      facility and PICU requirements over time. Various scenarios with different
      assumptions were explored. We compared these demands with estimates of maximal
      PICU capacity factoring in healthcare worker absenteeism as well as reported and
      more realistic estimates derived from semistructured telephone interviews with
      key stakeholders in ICUs in the study area. SETTING: All hospitals and intensive
      care facilities in the Northern Region in The Netherlands with near 1.7 million
      inhabitants, of whom approximately 25% is <18 yrs. MEASUREMENTS AND MAIN RESULTS:
      Using well-established modeling techniques, evidence-based medicine, and
      incorporating estimates from the Centers for Disease Control and Prevention and
      World Health Organization, we show that PICU capacity may suffice during an
      influenza pandemic. Even during the peak of the pandemic, most children requiring
      PICU admission may be served, even those who have nonflu-related conditions,
      provided that robust indications and decision rules are maintained, both for
      admission, as well as continuation (or discontinuation) of life support.
      CONCLUSIONS: We recommend that a model, with assumptions that can be adapted with
      new information obtained during early stages of the pandemic that is evolving, be
      an integral part of a preparedness plan for a pandemic influenza with new human
      transmissible agent like influenza A virus.

PMID- 20042910
TI  - The nature and characteristics of abdominal injuries sustained during children's
      sports.
AB  - OBJECTIVE: To increase the evidence base by characterizing various features of
      pediatric sports-related abdominal injuries. DESIGN: A review of the trauma
      database at The Children's Hospital at Westmead was undertaken for all abdominal
      injuries presenting to the emergency department between 2001 and 2006. SETTING:
      The Children's Hospital at Westmead is a tertiary-level pediatric trauma center
      servicing Sydney's west. It sees approximately 50,000 patients a year.
      PARTICIPANTS: Only those injuries occurring during an organized sport were
      included for analysis. Thirty-three of the original 513 patients were eligible
      for inclusion. MAIN OUTCOME MEASURES: The data collected included basic
      demographics, mechanism of injury, sport injury, time to presentation, length of
      stay, diagnoses, treatment, and complications. Injury severity scores were
      assigned retrospectively. RESULTS: Males sustained more injuries than females.
      Collisions and falls were the most common modes of injury. Rugby was the most
      common sport for injury. Most patients presented within 12 hours, and most
      presented with musculoskeletal injuries. Injury severity was usually mild;
      treatment, conservative; length of stay, short; and complications, uncommon. When
      characteristics were compared by sex, males had mostly collision injuries in high
      impact/contact sports, with females having more falls in other sports. When
      characteristics were compared by age, the only statistically significant
      difference was in the organ injured: older children had more single solid organ
      injuries, and younger children had more multiple and hollow viscus injuries.
      CONCLUSIONS: Sports-related abdominal injuries in children are mostly minor and
      not as common as other injury mechanisms. Despite this, they can be serious, with
      early diagnosis often delayed because of their subtle nature. Sports-related
      abdominal injuries in children require a high index of suspicion in the part of
      the clinician if they are to be recognized early and managed effectively.

PMID- 20042911
TI  - Potential impact of peripheral intravenous catheter placement on resource use in
      the pediatric emergency department.
AB  - OBJECTIVES: In an era of pediatric emergency department (PED) overcrowding and
      diminishing health care resources, routine peripheral intravenous (PIV) catheter
      placement in the pediatric population requires evaluation because it might
      directly impact PED efficiency. This study aims to determine the utility of
      routine PIV catheter placement during phlebotomy. METHODS: Electronic medical and
      billing records from 2 tertiary care PEDs during 1 year in patients 21 years or
      younger were analyzed. Data on the presence of PIV catheter placement in the PED,
      subsequent PIV catheter usage, chief complaint, and demographics were tabulated
      and analyzed. RESULTS: During the study period, there were 131,003 PED visits
      analyzed and 26,776 PIV catheters placed. Of those placed, 12,475 (47%) were not
      used. The median age of the patients who received a PIV catheter that was not
      subsequently used was 36 months. The frequency of unused PIV catheters correlates
      with lower initial triage acuity. The highest rate of unused PIV catheter was in
      those 1 to 6 months old (63%), followed by that in groups younger than 1 month
      (57%), older than 6 to 24 months (52%), and older than 24 months (41%).
      CONCLUSIONS: Nearly half of the PIV catheters placed in the PED were unused.
      Unused PIV catheters represent an inefficient use of limited resources that could
      be redistributed to improve ED efficiency, flow, and resource use.

PMID- 20042912
TI  - Antibiotic dosing for acute otitis media in children: a weighty issue.
AB  - BACKGROUND: The American Academy of Pediatrics 2004 guidelines on diagnosis and
      management of acute otitis media (OM) recommends use of high-dose amoxicillin for
      the treatment of acute uncomplicated OM. With rising childhood obesity,
      recommended amoxicillin dose of 80 to 90 mg/kg per day often exceed standard
      adult dose of 1500 mg/d. OBJECTIVE: To study prescribing patterns of primary care
      physicians for amoxicillin in the treatment of OM. To assess opinions of American
      Academy of Pediatrics subcommittee members who participated in guideline
      formulation. METHODS: This study had 2 parts. Part 1: Retrospective review of
      medical records of children visiting the hospital between April and June 2008 and
      with a diagnosis of OM and were prescribed amoxicillin. Part 2: Web-based survey
      of 14 members of the OM guidelines subcommittee. RESULTS: Part 1: Three hundred
      fifty-nine children were eligible, with a mean (SD) age of 3.2 (4.0) years and
      185 (51.5%) of whom were males. Children weighing 20 kg or less received higher
      mean daily dose of amoxicillin (74.2 vs 40.4 mg/kg per day, P < 0.00). Part 2:
      Nine (64.3%) subcommittee members responded to the survey. Most (77.8%) affirmed
      that the impact of obesity on high-dose amoxicillin recommendation was not
      discussed during guideline formulation. If a patient's estimated amoxicillin dose
      exceeded the standard adult dose (1500 mg/d), 66.7% members would prescribe the
      standard adult dose whereas 33.3% would prescribe the recommended dose of 80 to
      90 mg/kg per day. CONCLUSIONS: Primary care physicians prescribe a significantly
      lower-than-recommended amoxicillin dose in older children and those in the higher
      weight category. The opinion among subcommittee members regarding maximum dose
      specification of amoxicillin is varied.

PMID- 20042913
TI  - Pediatric metaxalone ingestions reported to Texas poison control centers, 2000
      2007.
AB  - OBJECTIVES: The purpose of this study was to describe the pattern of metaxalone
      ingestions by young children reported to poison control centers. METHODS: Cases
      were all metaxalone ingestions by patients aged 0 to 5 years reported to Texas
      poison control centers during 2000 to 2007. Cases with multiple substance
      ingestions and lack of follow-up were excluded. Cases were analyzed for selected
      demographic and clinical factors. RESULTS: Of 148 total cases, 56.8% were boys.
      The distributions by management site were 56.1% on-site, 22.3% already at/en
      route to a health care facility, and 21.6% referred to a health care facility.
      Final medical outcomes were no effect for 90.5% cases, minor effect for 8.1%,
      moderate effect for 0.7%, and major effect for 0.7%. Specific clinical effects
      reported were drowsiness (11), vomiting (3), agitation (2), rash (1%),
      tachycardia (1), and ataxia (1). CONCLUSIONS: Pediatric metaxalone ingestions
      reported to Texas poison control centers usually resulted in minor or no effect.
      Most ingestions did not require hospitalization.

PMID- 20042914
TI  - Evidence of methamphetamine exposure in children removed from clandestine
      methamphetamine laboratories.
AB  - OBJECTIVE: To determine whether asymptomatic children removed from clandestine
      methamphetamine laboratories have evidence of exposure to methamphetamine.
      METHODS: Retrospective chart review of children removed from law enforcement
      certified clandestine methamphetamine laboratories in the Tulsa area of Oklahoma
      and Sacramento County, California. Exposure was determined by positive urine
      toxicology for methamphetamine. RESULTS: One hundred four children were evaluated
      after removal from clandestine methamphetamine laboratories. Forty-eight children
      (46%) tested positive for methamphetamine. Timed urine results were known for 68
      of 104, with no child testing positive after 6.5 hours from being removed from
      the laboratory. No child required emergency medical treatment at the time urine
      samples were obtained. CONCLUSIONS: Almost half of the children in this sample
      had evidence of exposure to methamphetamine soon after removal from
      methamphetamine manufacturing environments. Further research is indicated to
      determine the health effects of subclinical methamphetamine exposure.

PMID- 20042915
TI  - Patient characteristics and provider practice patterns for emergency
      contraception in a pediatric emergency department.
AB  - OBJECTIVES: To describe epidemiologic and clinical characteristics of patients
      receiving emergency contraception (EC) in a pediatric emergency department (ED),
      practice variations for EC, and ED return visits after EC. METHODS: This single
      site study describes all patients who received oral EC (1.5-mg levonorgestrel) in
      the ED from January 1, 2003 to December 31, 2007. A chart review provided patient
      demographics, history, examination findings, treatment, and ED return visits
      within 7 days. RESULTS: There were 116 patients with a mean age of 13.7 years;
      half were white, and most (69.8%) had Medicaid. The most common presenting
      complaint was nonconsensual sex or sexual assault (87.9%). Most patients (89.6%)
      reported last sexual contact within 72 hours of presentation. Half of the
      patients (50%) received 1.5-mg levonorgestrel in a single dose, and there was a
      significant trend toward single-dose distribution during the study (P < 0.001).
      Patient presentation was most common from 8 pm to midnight (P < 0.001). Most
      received a pregnancy test (98.3%), a pelvic bimanual or speculum examination
      (81.9%), and prophylactic or immediate treatment of a sexually transmitted
      infection (88.8%). No prescriptions for future EC were given. One patient
      returned to the ED 1 day after receiving EC complaining of nausea and blurry
      vision. CONCLUSIONS: Reviewing recipients of EC from a pediatric ED suggests
      education is needed for both health care providers and adolescents. Although
      providers are generally following the most recent dosing guidelines,
      opportunities to prescribe EC to adolescent girls with complaints other than
      sexual assault seem to be missed.

PMID- 20042916
TI  - Make an M-PACT on asthma: rapid identification of persistent asthma symptoms in a
      pediatric emergency department.
AB  - OBJECTIVE: To develop and validate a brief assessment instrument for persistent
      asthma symptoms in a pediatric emergency department (ED) population. METHODS:
      Parents of children aged 1 to 18 years being discharged home after treatment for
      acute asthma in an urban children's hospital completed a 6-item screen for
      persistent symptoms that had been developed from national guidelines and
      previously validated. During a follow-up phone call 4 weeks after the ED visit,
      the instrument was repeated. An 8-item asthma-related quality-of-life (ARQOL)
      instrument was also administered at both times to assess construct validity. Item
      analysis assessed the performance of individual items and their combination
      versus the full instrument. RESULTS: Four hundred thirty-three children were
      enrolled, and 361 patients (83%) had complete data. Sensitivity and predictive
      value were calculated for the full screen and combination of items in detecting
      persistent symptoms at baseline and follow-up. A 3-item version included symptoms
      with activity, symptoms at night, and need for rescue albuterol. This version was
      96% sensitive (95% confidence interval, 92-99) for persistent symptoms compared
      with the 6-item screen, and 69% (95% confidence interval, 62-76) of the
      participants continued to report persistent symptoms 4 weeks after the visit. For
      both screens, subjects with persistent symptoms had significantly worse ARQOL
      score at baseline and follow-up. CONCLUSIONS: A brief screen can identify
      persistent symptoms in pediatric ED patients with good sensitivity compared with
      a longer instrument. Most of these patients will continue to report persistent
      symptoms and reduced ARQOL score 1 month after the ED visit and may be candidates
      for additional interventions in the ED to improve long-term asthma care.

PMID- 20042917
TI  - The Elimination of Haemophilus influenzae type b meningitis following conjugate
      vaccine introduction in Senegal.
AB  - BACKGROUND: Senegal introduced routine infant Haemophilus influenzae type b (Hib)
      conjugate vaccine during 2005. METHODS: We evaluated acute bacterial meningitis
      surveillance data among children 0 to 59 months of age collected during January
      2003 to September 2007 at the major pediatric referral hospital in the Dakar
      Region of Senegal. Hib vaccine effectiveness was assessed using a case-control
      design. RESULTS: A total of 1749 children with suspected bacterial meningitis
      were included in the current study of whom 142 (8%) had Hib identified. Among
      children less than age 1 year, the average annual Hib meningitis incidence
      decreased from 22 to 47 per 100,000 during 2003-2005 to 1.4 per 100,000 during
      2007, while pneumococcal meningitis incidence remained stable. Before vaccine
      introduction, calculated incidences varied over 4-fold between districts within
      the Dakar Region for the years 2003 to 2005. Following use of Hib vaccine,
      pneumococcus has now become the most common etiology of pediatric acute bacterial
      meningitis in Dakar region. CONCLUSIONS: Senegal successfully implemented Hib
      conjugate vaccine into their routine infant immunization program with a resultant
      near elimination of Hib meningitis burden.

PMID- 20042918
TI  - ACTH receptor (MC2R) promoter variants associated with infantile spasms modulate
      MC2R expression and responsiveness to ACTH.
AB  - OBJECTIVE: Adrenocorticotropin hormone (ACTH) has been the standard treatment to
      infantile spasms (IS). However, the mechanism of ACTH therapy is still unclear.
      ACTH exerts the function via melanocortin 2 receptor (MC2R). Our previous study
      showed a common 4-single nucleotide polymorphism (SNP) haplotype TCCT at the MC2R
      promoter was strongly associated with responsiveness to ACTH therapy, where these
      4 SNPs [rs1893219, rs1893220, rs2186944, and a novel SNP (T>C)] were mapped at
      position -853, -759, -7, and -2 bp based on the transcription start site of the
      MC2R gene. In this study, we further elucidated functional significances of the
      TCCT haplotype. METHODS: To evaluate whether the TCCT haplotype influences MC2R
      transcription levels, the luciferase reporter vector was used by a transient
      transfection. Expression of rat MC2R cDNA driven by the TCCT-carrying or TCCC
      carrying promoter was detected by the real-time quantitative reverse
      transcription-PCR. These assays were performed on cell lines cultured in absence
      or presence of ACTH. RESULTS: In the baseline, the light intensity of the
      luciferase reporter assay driven by the TCCT promoter was four times higher than
      that by the TCCC promoter. The intensity was dramatically increased in the pGL3
      TCCT after ACTH stimulation, compared to that in the pGL3-TCCC. MC2R expression
      assay showed a 5-fold increase in the TCCT promoter in presence of ACTH, compared
      with that in absence of ACTH. CONCLUSION: The results showed that the haplotype
      TCCT in MC2R promoter significantly led to increased MC2R expression and strong
      responses to ACTH, providing evidence of the molecular mechanism of ACTH therapy
      in IS.

PMID- 20042919
TI  - Limited sampling strategies for therapeutic drug monitoring of linezolid in
      patients with multidrug-resistant tuberculosis.
AB  - INTRODUCTION: Linezolid is a potential drug for the treatment of multidrug
      resistant tuberculosis but its use is limited because of severe adverse effects
      such as anemia, thrombocytopenia, and peripheral neuropathy. This study aimed to
      develop a model for the prediction of linezolid area under the plasma
      concentration-time curve from 0 to 12 hours (AUC0-12h) by limited sampling
      strategy to enable individualized dosing. PATIENTS AND METHODS: Fourteen patients
      with multidrug-resistant tuberculosis received linezolid twice daily as part of
      their antituberculosis treatment. Linezolid concentrations were determined at
      steady state by high-performance liquid chromatography tandem mass spectrometry
      before and at 1, 2, 4, 8, and 12 hours after dosing. Linezolid AUC0-12h
      population model and limited sampling models were calculated with MWPharm
      software. The correlation between predicted linezolid AUC0-12h and observed
      linezolid AUC0-12h was investigated by Bland-Altman analysis. RESULTS: A total of
      26 pharmacokinetic profiles were obtained. The median AUC0-12h was 51.8
      (interquartile range, 41.8-65.9) mg*h/L at 300 mg and 123.8 (interquartile range,
      100.9-152.5) mg*h/L at 600 mg, both twice daily. The most relevant model
      clinically for prediction of linezolid AUC0-12h used a linezolid trough
      concentration (r = 0.91, prediction bias = -2.9% and root mean square error =
      15%). DISCUSSION: The difference between choosing a trough concentration and two
      to three samples increased the correlation from 0.90 to 0.95 but appeared not
      clinically relevant because it did not result in different dosing advice.
      CONCLUSION: This study showed that linezolid AUC0-12h in patients with multidrug
      resistant tuberculosis could be predicted accurately by a minimal sampling
      strategy and could be used to individualize the dose.

PMID- 20042920
TI  - Investigation of the crossreactivity of mycophenolic acid glucuronide metabolites
      and of mycophenolate mofetil in the Cedia MPA assay.
AB  - The immunosuppressant mycophenolic acid (MPA) used for solid organ
      transplantation is predominantly metabolized to a pharmacologically inactive
      phenolic glucuronide (MPAG) and, to a lesser extent, to the pharmacologically
      active acyl glucuronide (AcMPAG). The recently introduced CEDIA Mycophenolic Acid
      Assay from Microgenics has been reported to overestimate MPA in clinical samples
      and crossreactivity with AcMPAG has been suspected. A detailed investigation of
      the crossreactivity of AcMPAG and the prodrug mycophenolate mofetil (MMF) in the
      CEDIA assay is presented using pure substances. In addition, MPA concentrations
      in plasma were compared with a validated high-performance liquid chromatography
      ultraviolet method. Plasma samples from kidney (KTx, n = 50), heart (HTx, n =
      50), and liver (LTx, n = 50) transplant recipients were analyzed by the CEDIA
      (MPA) and a high-performance liquid chromatography-ultraviolet method (MMF, MPA,
      MPAG, AcMPAG). Crossreactivity of MMF (0.93-46.3 mg/L), MPAG (50-1000 mg/L), and
      AcMPAG (0.5-10 mg/L) was investigated using spiked drug-free plasma. Method
      comparison was performed using Bland & Altman and Passing & Bablok analysis. The
      method bias was correlated to AcMPAG concentrations using Spearman's rank
      correlation. Crossreactivity with AcMPAG and MMF was concentration-dependent and
      reached 215% and 143%, respectively. There was no crossreactivity with MPAG. The
      CEDIA assay showed a mean positive bias of 36.3% in patient samples. The mean
      bias was lowest with HTx samples (15%), 41.7% with KTx samples, and highest with
      LTx samples (52.3%). There was a positive correlation between the method bias and
      AcMPAG concentrations (r = 0.829; P < 0.001). No MMF was detected in patient
      samples. The CEDIA overestimates MPA concentrations on average by 36%. This bias
      is mainly the result of AcMPAG as previously observed with the EMIT MPA assay. It
      should be considered that the putative therapeutic range for MPA with the CEDIA
      assay will be higher than the range using high-performance liquid chromatography.

PMID- 20042921
TI  - Unsuspected prenatal opioid exposure: long-term detection by alternative
      matrices.
AB  - We describe a suspicious case involving a previous heroin addict and her newborn
      child experiencing symptoms suggestive of withdrawal. Therapeutic drug monitoring
      was used to determine whether in utero exposure took place.

PMID- 20042922
TI  - Mycophenolic acid predose concentrations and renal function in a mouse model for
      progressive renal fibrosis.
AB  - Within the scope of this study, the potential antifibrotic effect of
      mycophenolate mofetil (MMF) on COL4A3-deficient mice as an animal model for
      progressive renal fibrosis was investigated regarding kidney function and
      survival. Thirty-five animals were randomly assigned to one of five groups and
      treated with doses of 0, 10, 50, 100, or 150 mg/kg MMF per day, respectively.
      When increasing somnolence was observed, indicating end-stage renal disease, the
      mice were euthanized and blood was obtained. Serum concentrations of creatinine,
      urea nitrogen, total protein, mycophenolic acid (MPA), and mycophenolic acid
      glucuronide (MPAG) were quantified. The kidney histology was examined using
      hematoxylin and eosin as well as trichrome staining. The mean overall survival
      was 65.9 (+/-6.1) days with no significant difference between the treatment
      groups (P > 0.05, Mantel-Cox test). Serum predose concentrations of MPA and MPAG
      showed considerable interindividual variability. There was no correlation between
      survival time and MPA or MPAG concentrations (P > 0.05, Spearman rank
      correlation). However, an apparent decrease in serum creatinine and urea nitrogen
      concentrations was observed at higher doses of MMF, eg, -54% for creatinine in
      the 150-mg/kg/day group compared with placebo. A highly significant reciprocal
      correlation between MPA concentrations and serum creatinine was demonstrated (P <
      0.01, r = -0.655, Spearman rank correlation). In conclusion, MMF may be a
      candidate drug for preserving kidney function in progressive renal fibrosis.

PMID- 20042923
TI  - Flexible nonlinear periodization in a beginner college weight training class.
AB  - McNamara, JM and Stearne, DJ. Flexible nonlinear periodization in a beginner
      college weight training class. J Strength Cond Res 24(1): 17-22, 2010-The purpose
      of this study was to determine the effect of a flexible nonlinear (FNL)
      periodized weight training program compared to a nonlinear (NL) periodized weight
      training program on strength and power. Sixteen beginner weight training students
      were randomly assigned to an FNL group (n = 8) or an NL group (n = 8). The
      exercise program included a combination of machines and free weights completed in
      30 minutes, twice per week, for 12 consecutive weeks. Both groups were assigned
      the same total training volume of 3,680 repetitions and the same total training
      repetition maximum assignments of 10, 15, and 20. The FNL group, however, was
      allowed to choose which day they completed the 10-, 15-, or 20-repetition
      workout. This was the only difference between the groups. Pre- and post-test
      measures included chest press, leg press, and standing long jump. The FNL group
      significantly improved by an average increase of 62 kg (p < 0.05), whereas the NL
      group only increased by an average of 16 kg in the leg press. The FNL group did
      not significantly differ in chest press or standing long jump performance when
      compared to the NL group. The conclusion from this study is that an FNL
      periodization program may be a highly effective method of training for improving
      leg strength. Coaches can immediately implement an FNL program by evaluating the
      readiness of an athlete immediately before his or her training session, then
      adjusting the assigned exercise intensity accordingly.

PMID- 20042924
TI  - Triathlon event distance specialization: training and injury effects.
AB  - We conducted a preliminary, questionnaire-based, retrospective analysis of
      training and injury in British National Squad Olympic distance (OD) and Ironman
      distance (IR) triathletes. The main outcome measures were training duration and
      training frequency and injury frequency and severity. The number of overuse
      injuries sustained over a 5-year period did not differ between OD and IR.
      However, the proportions of OD and IR athletes who were affected by injury to
      particular anatomical sites differed (p < 0.05). Also, fewer OD athletes (16.7
      vs. 36.8%, p < 0.05) reported that their injury recurred. Although OD sustained
      fewer running injuries than IR (1.6 +/- 0.5 vs. 1.9 +/- 0.3, p < 0.05), more
      subsequently stopped running (41.7 vs. 15.8%) and for longer (33.5 +/- 43.0 vs.
      16.7 +/- 16.6 days, p < 0.01). In OD, the number of overuse injuries sustained
      inversely correlated with percentage training time, and number of sessions, doing
      bike hill repetitions (r = -0.44 and -0.39, respectively, both p < 0.05). The IR
      overuse injury number correlated with the amount of intensive sessions done (r =
      0.67, p < 0.01 and r = 0.56, p < 0.05 for duration of "speed run" and "speed
      bike" sessions). Coaches should note that training differences between
      triathletes who specialize in OD or IR competition may lead to their exhibiting
      differential risk for injury to specific anatomical sites. It is also important
      to note that cycle and run training may have a "cumulative stress" influence on
      injury risk. Therefore, the tendency of some triathletes to modify rather than
      stop training when injured-usually by increasing load in another discipline from
      that in which the injury first occurred-may increase both their risk of injury
      recurrence and time to full rehabilitation.

PMID- 20042925
TI  - The effect of oral vs. Intravenous rehydration on circulating myoglobin and
      creatine kinase.
AB  - Physical activity of significant intensity and duration may cause varying degrees
      of skeletal muscle damage, but it is unclear whether mode of rehydration will
      attenuate muscle tissue disruption caused by exercise in the heat. To examine the
      effects of the mode of rehydration on markers of muscle damage (myoglobin and
      creatine kinase [CK]), 11 healthy active men (age = 23 +/- 4 years, body mass =
      80.9 +/- 3.9 kg, height = 180.5 +/- 5.4 cm) completed 4 experimental trials
      consisting of an exercise dehydration protocol (to -4% of baseline body mass),
      followed by a rehydration period (oral, intravenous [IV], oral and IV combined,
      and ad libitum), and finishing with an intense exercise challenge that included
      treadmill running and sprinting and a box lifting protocol. During rehydration,
      subjects returned to -2% of baseline body mass unless completing the ad libitum
      trial during which they consumed fluids as thirst dictated. Myoglobin (Mb) and CK
      were measured during euhydrated rest. Post-exercise blood was drawn at 1 and 24
      hours post exercise challenge for Mb and CK, respectively. Urine was collected
      during euhydrated rest and 1-hour post exercise challenge for measurement of Mb
      clearance. Mb concentrations increased significantly from pre (1.06 +/- 0.20,
      0.88 +/- 0.07, 1.15 +/- 0.25 and 0.92 +/- 0.06 nmol.L) to post (1.52 +/- 0.28,
      1.44 +/- 0.11, 1.71 +/- 0.45 and 1.58 +/- 0.39) for IV, oral, oral and IV
      combined, and ad libitum, respectively, but were not significantly different
      among trials. Serum CK concentrations remained within the normal physiological
      range for all trials. Thus, despite previous research that clearly indicates the
      benefit of ingesting fluids during exercise to attenuate muscle damage, there
      were no significant differences between the modes of rehydration on circulating
      Mb and CK.

PMID- 20042926
TI  - Gastrointestinal temperature increases and hypohydration exists after collegiate
      men's ice hockey participation.
AB  - The cold environments in which ice hockey players participate are
      counterintuitive to the predisposing factors of heat- and hypohydration-related
      illnesses. This population has received little consideration in hypohydration
      related illness risk assessments. Protective equipment, multiple clothing layers,
      and performance intensity may predispose these athletes to significant decreases
      in hydration and increases in core temperature. The purpose of this study was to
      measure hydration status and gastrointestinal temperature (T(GI)) in male ice
      hockey players during practice sessions that focused on pre-season skill
      development and cardiovascular conditioning. The study used a repeated measures
      design. Data were collected in a collegiate ice hockey rink (ambient temperature
      = 6.03 +/- 1.65 degrees C; relative humidity = 40.4 +/- 11.89%). Seventeen ice
      hockey players (age = 20.6 +/- 1.1, height = 180 +/- 5 cm, mass = 85.04 +/- 7.9
      kg) volunteered for this study. Urine-specific gravity (USG) and body weight were
      measured before and after two 110-minute practice sessions. Urine reagent strips
      measured USG. Calibrated CorTemp (HQ, Inc., Palmetto, FL, USA) radiofrequency
      telemetered thermometers collected T(GI) before, during, and after two 110-minute
      practice sessions. Individual participant sweat rates were calculated. Data from
      both sessions were pooled. T(GI) (p < 0.0001), and USG (p < 0.0001) increased
      over the 110-minute session. Post-exercise body weight (83.9 +/- 7.6 kg) was
      statistically lower (p < 0.001) than the pre-exercise weight (85.0 +/- 7.9 kg).
      Sweat rates were calculated to be 0.83 +/- 0.50 L.h(-1). These male ice hockey
      players become hypohydrated during participation potentially predisposing them to
      dehydration-related illnesses. This change in hydration status resulted in a
      gastrointestinal temperature increase and significant weight loss during
      activity. Prevention and rehydration strategies such as those developed by the
      American College of Sports Medicine and National Athletic Trainers' Association
      should be implemented to reduce the possibility of heat-related illness for this
      population.

PMID- 20042927
TI  - Effect of static and dynamic stretching on vertical jump performance in
      collegiate women volleyball players.
AB  - The purpose of this study was to determine the effect of stretching on peak jump
      height during a series of vertical jumps, specifically focusing on a) static
      stretching (SS), b) dynamic stretching (DS) and c) no stretching (NS) performed
      immediately before a series of countermovement vertical jumps (CMJ). Twelve
      female collegiate volleyball players (mean +/- SD; age 19.5 +/- 1.1 yr; height
      1.71 +/- 0.06 m; mass 71.3 +/- 8.54 kg) volunteered for this study. Data
      collection lasted a total of 3 weeks, and each subject performed all 3 stretching
      protocols, 1 session per week, with 1 week between sessions. The order of the
      stretching protocols was randomized for each subject. During each testing
      session, all subjects performed a 5-minute light jog as a warm-up, followed by 8
      minutes of 1 of the stretching protocols. One minute after the completion of each
      protocol, 5 maximal CMJ were performed on a force platform, with each jump
      separated by 1 minute of passive recovery. Jump heights were calculated by
      integrating the vertical force trace. There were no significant differences
      between the SS, DS, and NS conditions for any of the jumps (p > 0.05). Despite
      the lack of significant effects for the group, there were notable individual
      responses to each of the warm-up conditions. Practitioners should be aware of the
      individual responses of their athletes to different types of warm-up protocols
      before athletic performance and the possible impact of prescribing or eliminating
      certain exercises.

PMID- 20042928
TI  - The diagnosis-related group (DRG) system.

PMID- 20042929
TI  - The evolution of diagnosis-related groups (DRGs): from its beginnings in case-mix
      and resource use theory, to its implementation for payment and now for its
      current utilization for quality within and outside the hospital.
AB  - Policymakers are searching for ways to control health care costs and improve
      quality. Diagnosis-related groups (DRGs) are by far the most important cost
      control and quality improvement tool that governments and private payers have
      implemented. This article reviews why DRGs have had this singular success both in
      the hospital sector and, over the past 10 years, in ambulatory and managed care
      settings. Last, the author reviews current trends in the development and
      implementation of tools that have the key ingredients of DRG success: categorical
      clinical model, separation of the clinical model from payment weights, separate
      payment adjustments for nonclinical factors, and outlier payments. Virtually all
      current tools used to manage health care costs and improve quality do not have
      these characteristics. This failure explains a key reason for the failure, for
      example, of the Medicare Advantage program to control health care costs. This
      article concludes with a discussion of future developments for DRG-type models
      outside the hospital sector.

PMID- 20042930
TI  - Change in MS-DRG assignment and hospital reimbursement as a result of Centers for
      Medicare & Medicaid changes in payment for hospital-acquired conditions: is it
      coding or quality?
AB  - CONTEXT: In October 2008, the Centers for Medicare & Medicaid Services reduced
      payments to hospitals for a group of hospital-acquired conditions (HACs) not
      documented as present on admission (POA). It is unknown what proportion of
      Medicare severity diagnosis related group (MS-DRG) assignments will change when
      the International Classification of Disease, 9th Revision, Clinical Modification
      (ICD-9-CM) diagnosis code for the HAC is not taken into account even before
      considering the POA status. OBJECTIVES: The primary objectives were to estimate
      the proportion of cases that change MS-DRG assignment when HACs are removed from
      the calculation, the subsequent changes in reimbursement to hospitals, and the
      attenuation in changes in MS-DRG assignment after factoring in those that may be
      POA. Last, we explored the effect of the numbers of ICD-9-CM diagnosis codes on
      MS-DRG assignment. METHODS: We obtained 2 years of discharge data from academic
      medical centers that were members of the University Health System Consortium and
      identified all cases with 1 of 7 HACs coded through ICD-9-CM diagnosis codes. We
      calculated the MS-DRG for each case with and without the HAC and, hence, the
      proportion where MS-DRG assignment changed. Next, we used a bootstrap method to
      calculate the range in the proportion of cases changing assignment to account for
      POA status. Changes in reimbursement were estimated by using the 2008 MS-DRG
      weights payment formula. RESULTS: Of 184,932 cases with at least 1 HAC, 27.6% (n
      = 52,272) would experience a change in MS-DRG assignment without the HAC factored
      into the assignment. After taking into account those conditions that were
      potentially POA, 7.5% (n = 14,176) of the original cases would change MS-DRG
      assignment, with an average loss in reimbursement per case ranging from $1548
      with a catheter-associated urinary tract infection to $7310 for a surgical site
      infection. These reductions would translate into a total reimbursement loss of
      $50 261,692 (range: $38 330,747-$62 344,360) for the 86 academic medical centers.
      Those cases, for all conditions, with reductions in payment also have fewer
      additional ICD-9-CM codes associated. CONCLUSIONS: Removing HACs from MS-DRG
      assignment may result in significant cost savings for the Centers for Medicare &
      Medicaid Services through reduced payment to hospitals. As more conditions are
      added, the negative impact on hospital reimbursement may become greater. However,
      it is possible that variation in coding practice may affect cost savings and not
      reflect true differences in quality of care.

PMID- 20042931
TI  - Propensity score matching in the evaluation of drug therapy management programs:
      an illustrative analysis of a program for patients with hepatitis C virus.
AB  - This retrospective cohort analysis demonstrates the application of propensity
      score methods in the Be In Charge (BIC) program, a drug therapy management
      program for patients with hepatitis C. Data were drawn from BIC participant
      records and program utilization and from a longitudinal database of
      administrative claims for pharmacy and medical services. Eligible patients must
      have received peginterferon alfa-2b (PEG-IFN alfa-2b) and ribavirin, but analyses
      evaluated only PEG-IFN alfa-2b use; BIC enrollees were matched with patients not
      enrolled in BIC (controls). Adherence was measured on the basis of the number of
      injections dispensed and the proportion of patients for whom an average of at
      least 1 injection per week was dispensed during follow-up. BIC subjects refilled
      1.2 more injections than did controls (P < .001) within 12 weeks, 2.7 more (P <
      .001) within 24 weeks, and 6.7 more (P < .001) within 48 weeks. BIC enrollees
      were more likely than controls to refill the indicated dose (1 injection per
      week) within 12 weeks (72% vs 64%, P < .001), 24 weeks (52% vs 41%, P < .001),
      and 48 weeks (22% vs 13%, P = .002) of initiation. These data suggest that the
      BIC program may significantly improve adherence to PEG-IFN alfa-2b.

PMID- 20042932
TI  - Knowledge sharing and organizational learning in the context of hospital
      infection prevention.
AB  - Recently, hospitals that have been successful in preventing infections have
      labeled their improvement approaches as either the Toyota Production System (TPS)
      approach or the Positive Deviance (PD) approach. PD has been distinguished from
      TPS as being a bottom-up approach to improvement, as against top-down. Facilities
      that have employed both approaches have suggested that PD may be more effective
      than TPS for infection prevention. This article integrates organizational
      learning, institutional, and knowledge network theories to develop a theoretical
      framework for understanding the structure and evolution of effective knowledge
      sharing networks in health care organizations, that is, networks most conducive
      to learning and improvement. Contrary to arguments put forth by hospital success
      stories, the framework suggests that networks rich in brokerage and hierarchy
      (ie, top-down, "TPS-like" structures) may be more effective for learning and
      improvement in health care organizations, compared with a networks rich in
      density (ie, bottom-up, "PD-like" structures). The theoretical framework and
      ensuing analysis help identify several gaps in the literature related to
      organization learning and improvement in the infection prevention context. This,
      in turn, helps put forth recommendations for health management research and
      practice.

PMID- 20042933
TI  - Evaluating the quality of acute rehabilitation care for patients with spinal cord
      injury: an extended Donabedian model.
AB  - OBJECTIVE: In this study, the researchers examined the quality of rehabilitation
      care for patients with spinal cord injury (SCI), using an extension of
      Donabedian's structure, process, outcome model that included environmental and
      patient characteristic. METHODS: Cluster analysis, univariate variance analysis,
      and multilevel analysis were used to examine the quality of care for patients
      with SCI (N = 1974) enrolled in SCI Model Systems between 2000 and 2004. RESULTS:
      Patients were classified into low-, intermediate-, and high-functioning groups on
      the basis of admission functional status profiles as measured by the Functional
      Independence Measure (FIM). Patient profiles and therapy received were found to
      be related to outcomes measured by FIM gain. Care structure measured by patient
      volume was found to be negatively associated with outcomes, but facility-level
      therapist-bed ratios were not related to FIM gain. Medicare Inpatient
      Rehabilitation Facility Prospective Payment System (IRF PPS) interacted with
      patient profiles influencing FIM gain. CONCLUSION: The results from this study
      indicated a clear disconnection between the number of therapists and the amount
      of therapy delivered. This would suggest that potential inefficiency of therapy
      delivery due to the deployment and allocation of therapy services could be
      addressed by further consideration of patient profiles that reflect their
      specific needs and characteristics.

PMID- 20042934
TI  - Impact of online counseling on drug use: a pilot study.
AB  - PURPOSE: To examine the effect of online counseling abuse counseling on drug use
      among underserved patients. METHODS: Subjects were recruited from an Indian
      Reservation in Eagle Butte, South Dakota; a family court in Newark, New Jersey; a
      probation office in Alexandria, Virginia; and a co-occurring disorders treatment
      clinic in Washington, District of Columbia. Subjects were predominantly poor,
      undereducated, unemployed, court involved, or diagnosed with co-occurring
      psychiatric disorders. A total of 79 subjects volunteered to participate in the
      project. Subjects were randomly assigned to either a control group or an
      experimental group. The control and experimental groups were both issued an
      Internet-ready computer and 1 year of Internet service. Only the experimental
      group had access to online counseling intervention. Drug use was measured using a
      combination of self-usage reporting and supervised urine tests. RESULTS: Urine
      tests were available for 37% of subjects. Exit surveys containing self-reported
      usage were obtained from 54% of the subjects. Self-usage reports or urine test
      results were available from 70% of subjects. The difference of the rates of drug
      use in the control and experimental groups (as calculated from urine tests or
      through self-report) was not significantly different from zero, suggesting that
      online counseling had not led to a reduction in substance use. It is possible
      that the study lacked sufficient power to detect small differences in the rate of
      drug use in the experimental and control groups. CONCLUSIONS: Additional research
      is needed to establish the efficacy of online counseling in hard-to-reach
      populations.

PMID- 20042935
TI  - Routine assessment of patient-reported outcomes in behavioral health: room for
      improvement.
AB  - Outcomes assessment has become an important tool in assessing the quality of
      health care. To date, most quality initiatives have focused on adverse events,
      clinical processes, and/or cost variables. Considerably less attention has been
      paid to indices of clinical improvement, especially from a patient's perspective
      and in behavioral health settings. The relative inattention given to clinical
      improvement is attributable to a number of reasons, including (but not limited
      to) a lack of consensus regarding measures of improvement, few simple methods for
      data collection and analysis, and an inability to provide timely feedback. In
      this article, the authors describe a Web-based system designed to routinely
      collect quality-of-life ratings from patients in outpatient behavioral health
      clinics, allowing for real-time feedback at the patient levels regarding clinical
      improvement. The system also allows for administrative evaluation of overall
      clinic performance. The costs and benefits of this system are discussed.

PMID- 20042936
TI  - Patient satisfaction with the services of a pediatric digestive tract endoscopy
      unit: validation and application of a questionnaire.
AB  - Global satisfaction is the result of satisfaction with sequential connected
      caregiving activities administered according to current quality standards. We
      assessed patients' satisfaction with diagnostic digestive endoscopy via a
      questionnaire, asking for the state of information, organizational issues,
      anxiety, pain and discomfort, and medication side effects. A total of 157
      patients completed the questionnaire before and after the procedure, and the
      endoscopy nurse filled it during the procedure. Despite a high rate of global
      satisfaction, the questionnaire disclosed several items to improve: Patient
      information on medication intake before digestive endoscopy was insufficient.
      Patients would have appreciated more detailed description on the type of sedation
      during the procedure. While the amnesic effect of our sedation was good, the
      analgesic effect was less optimal. These results suggest that the questionnaire
      is a valid tool to assess both patients' satisfaction and quality of care in a
      pediatric endoscopy unit and that patient satisfaction does not necessarily
      reflect quality of care.

PMID- 20042937
TI  - A tutorial on activity-based costing of electronic health records.
AB  - As the American Recovery and Restoration Act of 2009 allocates $19 billion to
      health information technology, it will be useful for health care managers to
      project the true cost of implementing an electronic health record (EHR). This
      study presents a step-by-step guide for using activity-based costing (ABC) to
      estimate the cost of an EHR. ABC is a cost accounting method with a "top-down"
      approach for estimating the cost of a project or service within an organization.
      The total cost to implement an EHR includes obvious costs, such as licensing
      fees, and hidden costs, such as impact on productivity. Unlike other methods, ABC
      includes all of the organization's expenditures and is less likely to miss hidden
      costs. Although ABC is used considerably in manufacturing and other industries,
      it is a relatively new phenomenon in health care. ABC is a comprehensive approach
      that the health care field can use to analyze the cost-effectiveness of
      implementing EHRs. In this article, ABC is applied to a health clinic that
      recently implemented an EHR, and the clinic is found to be more productive after
      EHR implementation. This methodology can help health care administrators assess
      the impact of a stimulus investment on organizational performance.

PMID- 20042938
TI  - Reducing room turnaround time at a regional hospital.
AB  - Room turnaround time is a vital measure of performance for a number of service
      industries. For hospitals, reducing the room turnaround time leads to increased
      revenues as well as increased patient satisfaction. If a room is ready sooner, a
      waiting patient is required to spend less time in the emergency department. This
      article explores one hospital's approach to reduce room turnaround time. Process
      mapping techniques as well as heuristic approaches integrated into an existing
      bed-tracking system are examined. The article also explores the practical steps
      the hospital took to improve room turnaround time. Infection control is a
      requirement for any hospital; therefore, an examination of the current room
      cleaning procedures is included to verify that the improved room turnaround time
      did not come at the expense of infection control. Using initial data from 2004
      and current data from 2008, the magnitude of the reduction in room turnaround
      time is analyzed.

PMID- 20042941
TI  - Kinematics of sagittal spine and lower limb movement in healthy older adults
      during sit-to-stand from two seat heights.
AB  - STUDY DESIGN: A cross-sectional study to examine the sagittal kinematics of spine
      and lower limb movement during sit-to-stand (STS). OBJECTIVE: To describe the
      sagittal kinematics of the spine and lower limb in healthy older adults during
      STS from 2 seat heights. SUMMARY OF BACKGROUND DATA: Older adults with age
      related changes in the neuromusculoskeletal system are likely to have difficulty
      in STS. However, little is known about movement of the spinal regions and their
      interaction with the lower limb during STS, and the effect of seat height.
      METHODS: Thirty-two healthy older adults aged over 60 years were videotaped
      performing STS from 2 seat heights. A 2-dimensional video motion analysis system
      with a revised sagittal model was used to measure angular displacement and
      velocity for the cervical, thoracic, lumbar spine, and the lower limb joints.
      RESULTS: Concurrent flexion in the hip joint and lumbar spine was accompanied by
      extension in the thoracic, lower, and upper cervical spine as the trunk leaned
      forward. After the buttocks lifted off (LO) the chair, the movement interaction
      in the spine and hip joint was reversed. Some significant age-related changes
      during STS included downward head tilt at LO, decreased lumbar range of motion,
      and a large between-participant variation in the movement ratios. Statistically
      significant differences in the temporal parameters, angular displacement, and
      velocity were also found when standing from a lower chair. CONCLUSION: This study
      provides a detailed description of STS in healthy older adults, which has
      implications for rehabilitation of elderly patients who have difficulty with this
      activity. Clinicians need to be aware of the concurrent contribution of the hip
      joint and lumbar spine to trunk forward lean, the importance of thoracic
      extension during the pre-LO phase and the downward gaze at LO in healthy older
      adults.

PMID- 20042942
TI  - Psychological factors in the use of the neck disability index in chronic whiplash
      patients.
AB  - STUDY DESIGN: Cross-sectional clinical study. OBJECTIVE: Determine if
      psychological factors "fear avoidance behavior" and "pain amplification," along
      with age, gender, duration, and pain severity correlate with scores of self-rated
      disability in chronic whiplash sufferers. SUMMARY OF BACKGROUND DATA: The Fear
      Avoidance Model has gained acceptance in the understanding of whiplash-associate
      disorders (WAD). While the variables important in this model have been studied in
      acute/subacute samples and some small chronic samples, no study has explicitly
      investigated the role these and other psychosocial variables play in the self
      ratings of neck-related disability in chronic WAD sufferers. METHODS: Chronic WAD
      sufferers (>3 months) were recruited from private practice. No WAD IV subjects
      were included. Subjects completed a Neck Disability Index (NDI), Tampa Scale for
      Kinesiophobia (TSK), pain visual analogue scale, and pain diagram. Clinical and
      demographic data were also obtained. Univariate correlations were obtained with
      the Spearman rank correlation coefficient. Items achieving statistical
      significance on univariate analysis were loaded in a step-wise linear regression
      analysis. RESULTS: One hundred seven subjects were investigated (54 females),
      with a mean age of 45.4 (17) years and a mean duration of 13.4 (14.6) months.
      Fair to moderately strong correlations were obtained between the NDI and the TSK,
      pain visual analogue scale and pain drawing scores, but not with "duration." The
      Pain Diagram correlated with NDI scores and pain severity. A multivariate model
      accounting for 31% of the variance of the NDI scores (P < 0.001) was obtained
      with the TSK, pain severity, and pain drawing. CONCLUSION: It appears that
      important psychological factors (fear avoidance beliefs and pain amplification)
      do have some influence on self-ratings of disability in chronic WAD sufferers.
      This does not appear to be larger than that found in studies of acute/subacute
      subjects. The influence of these factors may plateau fairly early in the post-WAD
      period. There is some evidence that the Pain Diagram may provide insight into
      nonorganic pain behavior.

PMID- 20042943
TI  - Cauda equina syndrome in an eleven-month-old infant following sacrococcygeal
      teratoma tumor resection and coccyx excision: case report.
AB  - STUDY DESIGN: A case report of cauda equina syndrome (CES) in an 11-month-old
      infant, following sacrococcygeal teratoma tumor resection and coccyx excision
      leading to a spinal epidural hematoma (SEH). OBJECTIVE: To illustrate a rare case
      of CES and SEH in an infant, and discuss the need for sealing access to the
      spinal canal after sacrococcygeal surgical resection and reconstruction. SUMMARY
      OF BACKGROUND DATA: To the authors' knowledge, this is the youngest patient
      reported to develop a SEH and CES, and the only patient reported in the
      literature to develop a SEH after coccyx excision. METHODS: Seventeen days after
      undergoing sacrococcygeal tumor resection and coccyx excision, the patient
      presented to the emergency room with a large distended bladder, loss of rectal
      tone, and significant weakness in the lower extremities. Magnetic resonance
      imaging of the thoracic and lumbar spine showed a large lesion in the dorsal
      epidural space extending from T12 to the tip of the communicating with the prior
      operative site by means of the previous coccyx resection. The infant was
      emergently brought to the operating room for decompression. RESULTS: The patient
      was discharged 6 days later with diminished neurologic function, but demonstrated
      significant improvement over the next 18 months and currently remains disease
      free and neurologically normal at age 7. CONCLUSION: This case demonstrates the
      need for future examination of sacrococcygeal surgical resection and subsequent
      reconstruction of excised structures to decrease the risk of communication with
      the epidural space.

PMID- 20042944
TI  - Postoperative cervical cord compression induced by hydrogel (DuraSeal): a
      possible complication.
AB  - STUDY DESIGN: A retrospective case report. OBJECTIVE: To raise the issue of
      DuraSeal for dural tear repair; to raise the issue of the potential for fatal
      consequences, if not considered to be an issue around and after surgery; and to
      illustrate this with a case. SUMMARY OF BACKGROUND DATA: Cerebrospinal fluid leak
      is a potential complication of spinal, and posterior fossa surgery. Leakage may
      be caused by inadvertent dural tears during decompressive laminectomy or
      extradural spinal approaches, for spinal surgery. We present the case of a
      complication as a result of repair for dural tear with hydrogel. METHODS:
      History, focused neurologic examination with pre- and postoperative magnetic
      resonance scan images. RESULTS: C5-C6 anterior cervical discectomy, and fusion
      with a standard commercial PEEK space cage. Intraoperatively there was a small
      cerebrospinal leak when excising the posterior longitudinal ligament. Surgicel
      and DuraSeal were used to seal this. The patient developed a quadriparesis after
      surgery which was a result of expansion of the hydrogel seen on MRI and at re
      exploration. CONCLUSION: Hydrogel is now described for the second time to cause
      potentially fatal expansion.

PMID- 20042945
TI  - Brown-Sequard syndrome caused by type III odontoid fracture: a case report and
      review of the literature.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To present the second case of Brown-Sequard
      syndrome (BSS) produced by type III odontoid fracture managed by conservative
      treatment. SUMMARY OF BACKGROUND DATA: The occurrence of BSS due to odontoid
      fracture is scarce. So far 6 cases have been reported, and only 1 is produced by
      type III odontoid fracture. The possible pathophysiology, clinical course and
      treatment outcome have been rarely discussed. METHODS: A 39-year-old man
      presented with weakness of his left arm and leg, mild neck pain, and impaired
      proprioceptive and light touch sensations below the left C2 dermatome. There were
      decreased pain and temperature sensations below the right C4 dermatome too.
      Computerized tomography showed odontoid type III fracture with posterior
      displacement at that level. Magnetic resonance imaging presented focal
      hyperintensity around the C2 vertebral level. High dose of prednisolone, close
      reduction with Gardner-Wells tong skull traction, following external
      stabilization by Halo-Vest and rehabilitation therapy were applied. RESULTS:
      Complete resolution of neck pain and significant improvement of motor and sensory
      functions, i.e., light touch and proprioception, were shown 2 months after spinal
      injury. Impaired temperature discrimination persisted, however. CONCLUSION: BSS
      is rarely caused by type III odontoid fracture and this is the second report.
      Conservative intervention is advantageous for both type III odontoid fracture and
      BSS which is consistent with previous results.

PMID- 20042947
TI  - Langerhans cell histiocytosis of the cervical spine: a single Chinese institution
      experience with thirty cases.
AB  - STUDY DESIGN: A retrospective study of cervical Langerhans cell histiocytosis
      (LCH). OBJECTIVE: To evaluate the safety and efficiency of the present diagnosis
      and treatment strategy. SUMMARY OF BACKGROUND DATA: The diagnosis and treatment
      protocols are still controversial for the rarity of cervical LCH. METHODS: Thirty
      patients with cervical LCH were diagnosed in the past 10 years. Biopsy was
      routinely performed to establish the final diagnosis before treatment.
      Immobilization was usually the first choice. Low-dose radiotherapy was suggested
      for cases with solitary marked bony erosion and/or soft tissue extension, and
      chemotherapy for cases with multiple lesions. Surgery was preserved for suspected
      malignancy, neurologic deficits, severe deformity, and/or instability. RESULTS:
      The mean age at diagnosis was 14.2 (range: 1.5-41) years old. Neck pain (96.7%)
      was the most common symptom, followed by restricted motion (70%), neurologic
      symptoms (36.7%), and torticollis (30%). Four cases had multiple lesions.
      Fourteen cases had atlantoaxial lesion and 16 cases were subaxial. The lesion
      extended to paravertebral soft tissue in 40% cases, to epidural space in 30%, to
      pedicle and/or transverse process in 56.3%. One case had endplate destruction.
      The accuracy of percutaneous needle biopsy under CT guidance was 91.2%. Eighteen
      patients had conservative treatment and 12 underwent operation. Three cases
      involving C2 vertebral body had fixed atlantoaxial anterior dislocation. Another
      3 cases with atlantoaxial lateral mass destruction had spontaneous fusion.
      Eighteen patients had conservative treatment (1 only by immobilization, 13 by
      radiotherapy, 2 by chemotherapy, and 2 by combined chemotherapy and radiotherapy)
      and 12 underwent operation. All the initial symptoms were resolved, and there was
      no recurrence. From retrospective view, the surgical procedure might be avoided
      in 60% cases. Twenty-five cases had an average 61.6-month follow-up. In cases
      with severe bony collapse, the vertebral height ratio increased from 20.0% to
      44.9% and the lateral mass height ratio from 22.2% to 56.8%. CONCLUSION: Cervical
      LCH lesions often extend to paravertebral soft tissue, epidural space, pedicles,
      and even to the endplate and lamina. Needle biopsy under CT guidance is safe and
      effective. The prognosis of cervical LCH is generally fair. Conservative
      treatment is usually enough and surgery should be reserved for major neurologic
      defects like myelopathy or monoparesis.

PMID- 20042946
TI  - A rare anesthetic complication involving central line access during lumbar spine
      surgery: a case report and review.
AB  - STUDY DESIGN: A case report describing a rare perioperative complication
      involving the intrathoracic placement of a central venous catheter during spine
      surgery leading to hemodynamic instability. OBJECTIVE: To review the efficacy of
      central line use in perioperative spine patients and to describe the diagnosis,
      emergent treatment, and postoperative care of a unique case of intrathoracic
      extravasation of propofol. SUMMARY OF BACKGROUND DATA: Although placement of
      central line access is a safe procedure, complications can occur. A case in which
      a venous catheter delivering propofol into the thorax has never been documented.
      METHODS: A 48-year-old woman presented for revision spine surgery, and a central
      line was placed. After placement of spinal instrumentation, she became
      hemodynamically unstable secondary to mediastinal compression caused by pressure
      from intraoperative propofol and fluid insufflation. RESULTS: A chest tube was
      placed, and with aggressive pulmonary toilet and physical therapy, she did well
      and was discharged without noted symptoms. CONCLUSION: The efficacy of central
      line use should be carefully considered in perioperative spine surgery, and in
      patients with significant risk factors, placement of central venous access should
      be radiographically confirmed.

PMID- 20042949
TI  - Where is the wisdom in healthcare?: the "wizard of oz": heart, brain, and
      courage.

PMID- 20042950
TI  - Cartilage oligomeric matrix protein in canine spinal cord appears in the
      cerebrospinal fluid associated with intervertebral disc herniation.
AB  - STUDY DESIGN: Cerebrospinal fluid (CSF) from dogs with intervertebral disc
      herniation (IVDH) were analyzed using a specific antibody against cartilage
      oligomeric matrix protein (COMP). Immunolocalization and genetic expression of
      COMP were also examined in the spinal cords of mouse, rat, and dog. OBJECTIVE: To
      investigate the hypothesis that COMP is present in CSF of dogs with IVDH, and the
      clinical relevance of COMP expression in CSF as a potential biomarker of spinal
      cord injury. SUMMARY OF BACKGROUND DATA: In dog IVDH, diagnostic imaging is
      useful for determining the spinal cord compression, but less useful for
      assessment of traumatic degeneration. Aggrecan, a well-known component of
      cartilage matrix, is increased in CSF from cases of neural damage and
      inflammation of the spinal cord. METHODS: CSF from the cisterna magna (C-CSF) and
      the lumbar spine (L-CSF) of 19 dogs with IVDH and 5 normal dogs were analyzed
      using inhibition enzyme-linked immunosorbent assay (ELISA) and immunoblotting
      with an antibody cross-reactive with dog COMP. Samples of normal spinal cord from
      mouse, rat, and dog were also prepared for immunohistochemistry and in situ
      hybridization. RESULTS: ELISA values were significantly higher for L-CSF than for
      C-CSF in dogs with IVDH, whereas there was no significant difference between them
      in normal dogs. Immunoblots of L-CSF samples revealed positive bands of
      approximately 500 kDa in 6 cases of IVDH (positive cases), but no signal in
      negative cases. ELISA values were significantly higher in the positive cases than
      in the negative cases. Both COMP protein and mRNA were present at high levels in
      the gray matter of the spinal cord in all species. CONCLUSION: In dog IVDH,
      release of COMP from the spinal cord in association with injury may lead to COMP
      accumulation in L-CSF posterior to the site of disc extrusion, and therefore
      might be a predictive marker of spinal cord injury.

PMID- 20042951
TI  - The reactions of glial cells and endoneurial macrophages in the dorsal root
      ganglion and their contribution to pain-related behavior after application of
      nucleus pulposus onto the nerve root in rats.
AB  - STUDY DESIGN: Controlled, interventional, animal study. OBJECTIVE: To observe the
      reaction of glial cells and endoneurial macrophages in the dorsal root ganglion
      (DRG) after application of nucleus pulposus (NP) and investigate whether
      activated DRG glial cells play a role in the pathogenesis of neuropathic pain.
      SUMMARY OF BACKGROUND DATA: Peripheral nerve injury activated DRG and spinal cord
      glial cells and several cytokines and neurotrophins released from these activated
      glial cells might induce pain hypersensitivity. METHODS: Adult male Sprague
      Dawley rats were used. NP harvested from the tail was applied to the left L5 DRG.
      Behavioral testing was performed to investigate the mechanical withdrawal
      threshold. The numbers of activated satellite glial cells and endoneurial
      macrophages were counted, and the expressions of tumor necrosis factor-alpha (TNF
      alpha) and glial cell-line derived neurotrophic factor (GDNF) were examined by
      double-labeled immunohistochemistry and immunoblotting. RESULTS: The mechanical
      withdrawal threshold was significantly decreased for 28 days and then gradually
      recovered (P < 0.05). Long-term activation of endoneurial macrophages and
      satellite glial cells in the DRG was observed, and the reactions of these cells
      correlated well with pain-related behavior. TNF-alpha was expressed in both
      endoneurial macrophages and activated satellite glial cells, and TNF-alpha
      expression was significantly increased in the early stage (P < 0.05). Activated
      satellite glial cells also expressed GDNF, and its expression was significantly
      increased and persisted for 28 days (P < 0.05). CONCLUSION: Activation of DRG
      glial cells and endoneurial macrophages plays an important role in the
      pathogenesis of the neuropathic pain state. TNF-alpha actively released from
      activated glial cells and endoneurial macrophages in the DRG might initiate and
      maintain the neuropathic pain together with TNF-alpha derived from the applied
      NP. In the recovery phase, persistent expression of GDNF from activated satellite
      glial cells might play an important role to restore the function of damaged
      neurons and recover from neuropathic pain.

PMID- 20042952
TI  - Computed tomographic validation of the porcine model for thoracic scoliosis.
AB  - STUDY DESIGN: Computed Tomographic Analysis of the Porcine Scoliosis Model.
      OBJECTIVE: To describe the spinal and rib cage modifications using computed
      tomography (CT). SUMMARY OF BACKGROUND DATA: Optimal development of nonfusion
      techniques for treatment of adolescent idiopathic scoliosis (AIS) requires a
      reliable large animal model that achieves spinal and rib cage modifications
      similar to AIS. Previous work has described the global 3-dimensional nature of
      the progressive deformity. METHODS: This IACUC-approved study includes 11
      extracted scoliotic spines from a previous investigation. Scoliosis was induced
      through unilateral posterior ligament tethering of the spine via pedicle screw
      fixation, and ipsilateral rib cage tethering. CT analysis was used to quantify
      rib cage asymmetry, axial rotation, and wedging of the apical functional unit (2
      vertebrae and intervening disc) for each specimen. RESULTS: The mean coronal Cobb
      angle was 55.7 degrees (n = 11). Vertebral and intervertebral heights of the
      apical functional unit demonstrated convex heights (untethered) were always
      larger than concave (tethered) heights (P < 0.05). Axial rotation was maximal
      (mean, 20 degrees ) at 1 to 2 levels distal to the coronal apex. Maximal rib cage
      asymmetry was demonstrated at the transverse apex with significant coupling of
      the rotational and rib cage modifications (r = 0.82). A large initial Cobb index
      (tether tension) was significantly correlated with vertebral and intervertebral
      wedging and coronal curve progression. CONCLUSION: The present study has used CT
      analysis to analyze spinal and rib cage modifications in the Porcine Scoliosis
      Model. Placement of a unilateral ligamentous spinal tether combined with concave
      rib cage ligament tethering during the rapid growth stage of the Yorkshire pig
      results in significant apical vertebral and intervertebral wedging and rotational
      and rib cage modifications. The porcine model is a reliable and duplicable model
      for scoliosis, which bears significant similarities to AIS.

PMID- 20042953
TI  - Biomechanical evaluation of the kinematics of the cadaver lumbar spine following
      disc replacement with the ProDisc-L prosthesis.
AB  - STUDY DESIGN: Biomechanical study of the ProDisc-L in a cadaveric model under
      pure moment loading. OBJECTIVE.: To determine the kinematic properties of a
      lumbar spine motion segment and the adjacent level following ProDisc-L disc
      replacement in the cadaveric spine. SUMMARY OF BACKGROUND DATA: Total disc
      replacement is intended to preserve native motion, in an attempt to prevent
      accelerated adjacent segment degeneration. The quality and quantity of the motion
      following TDR may have important consequences on the facet joints of the same
      motion segment, as well as the motion at the prosthetic component interface.
      METHODS: Ten cadaveric lumbar spines were radiographed (L3-L5) and tested under
      pure moments (+10 Nm to -10 Nm) with an applied follower load (200 N). Load
      deformation was tested in flexion/extension, lateral bending (LB), and axial
      rotation (AR). Range of Motion (ROM) data were recorded. Superior adjacent disc
      pressure (L3-L4) was measured using subminiature pressure transducers. The L4-L5
      disc was subsequently instrumented with a ProDisc-L. Radiographs and
      biomechanical tests were repeated. RESULTS: Disc replacement significantly
      reduced extension (ROM 2.2 degrees +/- 0.5 degrees before and 1.2 degrees +/- 0.7
      degrees after instrumentation) (P = 0.001), but not flexion (ROM 5.6 degrees +/-
      3.1 degrees before and 6.2 degrees +/- 1.2 degrees after) (P = 0.34). Combined
      flexion/extension motion was marginally reduced (P = 0.517). LB ROM (7.4 degrees
      +/- 2.0 degrees ) was marginally reduced (P = 0.072) following instrumentation
      (6.2 degrees +/- 2.5 degrees ), while ROM in AR (3.4 degrees +/- 1.1 degrees )
      was significantly increased (4.4 degrees +/- 1.2 degrees ) (P = 0.001). Superior
      adjacent segment ROM was preserved.No significant differences in disc pressure
      were observed at the adjacent motion segment before (199 kPa at maximum flexion
      and 171 kPa at maximum extension) or after disc replacement (252 kPa and 208 kPa,
      respectively). CONCLUSION: In cadaveric spines, ROM of operated and adjacent
      motion segments was preserved following ProDisc-L insertion. Excision of the
      anterior anulus may increase laxity, which is taken up by the restoration of disc
      height and lordosis, at the cost of a moderate loss of flexion/extension motion.
      Adjacent segment kinematics were unaffected following TDR.

PMID- 20042954
TI  - A new performance test for cervical myelopathy: the triangle step test.
AB  - STUDY DESIGN: Our original performance test for evaluating the severity of
      cervical myelopathy, the triangle step test (TST), was introduced along with an
      assessment of its validity. OBJECTIVE: The TST was designed to evaluate the lower
      extremity motor function objectively and quantitatively. This study aimed to
      assess the validity of the test by analyzing the relation to the other analytic
      methods. SUMMARY OF BACKGROUND DATA: Several rating scales and performance tests
      have been proposed to evaluate the severity of cervical myelopathy. Simple
      walking test is useful; however, the test is limited for the patients who can
      walk safely. METHODS: Each subject sitting on a chair was instructed to step on
      marks at each apex of a triangular board and the number of steps in 10 seconds
      was counted for each foot. The subjects were 270 cervical myelopathy patients who
      had visited our hospital since 2002. As a control group, 60 healthy adults also
      underwent this test. All subjects were simultaneously evaluated by the Nurick
      score, the Japan Orthopedic Association score and the finger grip and release
      test. An assessment of the effect of surgery was analyzed for 94 patients who
      underwent surgical treatments. RESULTS: The mean of the lower count for each
      subject (TST score) in the control group was 25.4 +/- 3.7 steps, which was
      superior to 18.4 +/- 5.2 steps for myelopathy patients. TST score significantly
      correlated to the other analytic measures for cervical myelopathy. Regarding the
      effect of surgery, a performance of 16.7 +/- 4.5 steps before surgery improved to
      21.2 +/- 4.9 steps at follow-up. Patients who could step more than 20 times
      before surgery, showed greater neurologic recovery. CONCLUSION: TST score
      correlated with other analytic methods for cervical myelopathy. This test is very
      useful to quantitatively evaluate lower extremity function and its improvement
      following surgical intervention.

PMID- 20042955
TI  - Short segment coronal plane deformity after two-level lumbar total disc
      replacement.
AB  - STUDY DESIGN: Case series of 2-level lumbar disc arthroplasties treated by the
      authors. OBJECTIVE: Identify a potentially significant failure rate of 2-level
      disc arthroplasty due to coronal plane instability. SUMMARY OF BACKGROUND DATA:
      Arthrodesis remains the standard for surgical treatment of degenerative disc
      disease, despite concerns about adjacent level degeneration and persistent
      postoperative pain in some patients. Total disc arthroplasty has been proposed as
      a way to reduce these problems. Intermediate follow-up of 1-level procedures
      demonstrates promising safety and improved pain scores. Some surgeons are
      expanding the surgical indications to more challenging settings, including
      multilevel disease. METHODS: We report here our experience with 4 cases of failed
      2-level disc arthroplasty. RESULTS: We have seen 4 patients with failed 2-level
      lumbar arthroplasty, of those 2 performed in Germany and 2 performed in our state
      by 2 different experienced spine surgeons. The 2 local cases represent 29% (2/7)
      of all 2-level CHARITE arthroplasties performed within our state. All 4 patients
      presented within 11 to 13 months of implantation with increased back pain and
      radicular symptoms. The mechanism of failure was coronal instability due to small
      deviations of the prostheses from a midline position in all 4 cases. CONCLUSION:
      Disc arthroplasty appears to be a safe and effective treatment for 1-level lumbar
      degenerative disc disease. Although promising biomechanical reports of 2-level
      models are emerging, we are concerned by the rate of failures of 2-level
      arthroplasty that we are seeing. It appears that the potential for coronal plane
      instability increases as the number of levels increases. Given the costs and
      risks associated with these procedures, we feel that this issue deserves the
      attention of the spine surgery community despite the limited numbers in this
      report.

PMID- 20042956
TI  - Prevalence, distribution, and morphology of ossification of the ligamentum
      flavum: a population study of one thousand seven hundred thirty-six magnetic
      resonance imaging scans.
AB  - STUDY DESIGN: Large scale, cross-sectional imaging study of a general population.
      OBJECTIVES: To evaluate the prevalence, morphology, and distribution of
      ossification of the ligamentum flavum (OLF) in a population, and synthesize the
      scientific literature on the prevalence of OLF and some factors associated with
      its occurrence. SUMMARY OF BACKGROUND DATA: OLF is a rare disease in which the
      pathogenesis has not been conclusively established. Little is known about its
      epidemiology. To date, there is no study that comprehensively assessed the
      distribution and prevalence of OLF in the whole spine using magnetic resonance
      imaging (MRI). METHODS: A total of 1736 southern Chinese volunteers (1068 women;
      668 men) between 8 and 88 years of age (mean, 38 years) were recruited by open
      invitation. MRI was administered to all the participants. T2-weighted, 5-mm spin
      echo MRI sequences of the whole spine were obtained. Presence of OLF was
      identified as an area of low signal intensity in the T2 sagittal sequence located
      in the posterior part of the spinal canal, and subsequently confirmed by computed
      tomography scans showing areas of ossification within the ligamentum flavum. The
      distribution of OLF was classified into 3 types: the isolated type, continuous
      type, and noncontinuous type. While the morphology of the lesion was classified
      into triangular, round, and beak shapes based on the pattern of ossification on
      T2-weighted sagittal MRIs. RESULTS: OLF was identified in a total of 66 subjects
      or 3.8% of the population (52 women and 14 men). In 45(68.2%) cases, OLF was
      present at a single-level (isolated type), whereas in 21 (31.8%) cases OLF was
      present at multiple levels. The isolated type was found in 45 (68.2%) cases,
      continuous type in 11 (16.7%), and noncontinuous type in 10 (15.2%). The most
      common site of involvement is the lower thoracic spine, but they can also occur
      in the upper thoracic spine. The majority of the segments had a round morphology
      (n = 75: 81.5%), while 17 (18.5%) segments were triangular in shape. A literature
      review of the past 26 years showed only 4 reports on the prevalence of OLF, all
      were in special patient groups. CONCLUSION: Case reports have described
      postoperative paraplegia from failure to identify and decompress all stenotic
      segments of OLF. This study demonstrated that OLF is not uncommon, and that some
      15% of the lesions are noncontinuous, and therefore could be missed. The authors
      recommend that for patients undergoing surgical decompression for 1 level of OLF,
      the whole spine should be routinely screened for other stenotic segments. Failure
      to do so could result in paraplegia from the nondecompressed levels.

PMID- 20042957
TI  - Adolescent idiopathic scoliosis treated with open instrumented anterior spinal
      fusion: five-year follow-up.
AB  - STUDY DESIGN: A multicenter prospective database was queried for patients who
      underwent open instrumented anterior spinal fusion (OASF) for treatment of
      primary thoracic (Lenke 1) adolescent idiopathic scoliosis (AIS). OBJECTIVES: To
      present the intermediate radiographic and pulmonary function testing (PFT) data
      from patients who underwent OASF using modern, rigid instrumentation. SUMMARY OF
      BACKGROUND DATA: Anterior spinal fusion is an excellent method to correct the 3
      dimensional deformity produced by AIS. Modern instrumentation consisting of
      stronger metals, unthreaded rods, and dual rod systems should theoretically
      decrease the incidence of rod breakage, pseudarthrosis, and loss of correction
      seen in earlier OASF studies. The paucity of intermediate and long-term data
      prevents surgeons and patients from making an informed decision regarding the
      true incidence of these complications. METHODS: Of 101 potential patients who
      underwent OASF with a minimum 5-year follow-up, 85 (85%) were studied. Standing
      radiographs were analyzed before surgery and at first standing erect, 2-year, and
      5-year follow-up. PFT data were collected before surgery and at 5 years after
      surgery. RESULTS: Complete 5-year follow-up was obtained in 85 patients. Five
      years after surgery, the mean coronal correction was 26 degrees (51%; P < 0.05)
      and the thoracolumbar/lumbar curve improved 16 degrees (51%). There was a 9
      degree (P < 0.001) increase in kyphosis, and there were 9 patients (11%) in whom
      the C7 plumb line translated >2 cm. There was a 6.7% decrease in predicted FEV1
      over the 5-year period, from 75.5% +/- 13% before surgery to 68.8% +/- 2% at 5
      year follow-up (P = 0.007); however, there was no significant change in FVC.
      There were 3 significant adverse events: 1 implant breakage requiring reoperation
      and 2 cases of progression of the main thoracic curve requiring reoperation.
      CONCLUSION: OASF is a reproducible and safe method to treat thoracic AIS. It
      provides good coronal and sagittal correction of the main thoracic and
      compensatory thoracolumbar/lumbar curves that is maintained with intermediate
      term follow-up. In skeletally immature children, this technique can cause an
      increase in kyphosis beyond normal values, and less correction of kyphosis should
      be considered during instrumentation. As with any procedure that employs a
      thoracotomy, pulmonary function is mildly decreased at final follow-up.

PMID- 20042958
TI  - A variability study of computerized sagittal sacral radiologic measures.
AB  - STUDY DESIGN: A radiographic study was conducted to investigate the accuracy of
      computer-assisted measurement of sacral morphology in a population with
      developmental L5-S1 spondylolisthesis. OBJECTIVE: The purpose of this study was
      to evaluate the inter- and intraobserver variability of computer measurements of
      sacral morphology. SUMMARY AND BACKGROUND DATA: Recent studies have shown
      differences in sacral morphology among patients with spondylolisthesis. The
      sacral table angle (STA) is a fundamental sacral anatomic parameter that is
      specific and constant to each individual, while the S1 superior and S2 inferior
      angles are defined as anatomic measures specific to S1 and S2. Sacral kyphosis
      measured by Ferguson or Cobb method has also been used to evaluate the sagittal
      shape of the sacrum. Currently, computerized measures are gaining popularity for
      the study of sagittal balance, but their reliability especially in sacral
      morphology has never been properly evaluated. METHODS: The standing lateral
      radiographs of 30 adolescents were randomly selected from the radiographic
      database of our institution: 10 radiographs of asymptomatic individuals, 10 of
      subjects with low grade L5-S1 spondylolisthesis and 10 with high grade L5-S1
      developmental spondylolisthesis. Three surgeons measured sacral morphologic
      variables on the 30 radiographs at 2 occasions, with a 15 days interval between
      the 2 sessions, using a computer assisted technique. Intraclass correlation
      coefficients (ICCs) were used for statistical analysis. RESULTS: The ICC values
      measured within observers varied between 0.951 to 0.995, whereas the ICC measured
      between observers varied between 0.957 to 0.995. There was a slight decrease of
      the ICC measured in the high grade L5-S1 spondylolisthesis group compared to the
      normal subjects. However, the difference was not statistically significant.
      CONCLUSION: These results confirm the reliability and repeatability of computer
      assisted angular measurement of sacral morphology in subjects with L5-S1
      spondylolisthesis, even in the presence of lumbosacral junction dysplasia. The
      use of computerized measurements can be recommended for the evaluation of the
      sagittal sacral anatomy in future clinical and research studies.

PMID- 20042959
TI  - Morphometric analysis of neurocentral synchondrosis using magnetic resonance
      imaging in the normal skeletally immature spine.
AB  - STUDY DESIGN: Morphometric analysis of the neurocentral synchondrosis (NCS) using
      magnetic resonance imaging in the normal infantile and juvenile patients.
      OBJECTIVES: To assess the developmental stages of the neurocentral synchondrosis
      (NCS) by determining the age at which closure of the NCS occurs at specific
      levels of the spine and to evaluate whether symmetric growth of the NCS occurs
      during the different developmental stages in normal immature spine. SUMMARY OF
      BACKGROUND DATA: The function and developmental stage of the NCS are
      controversial because of a lack of agreement on the exact age of closure. To
      date, most authors believe that the NCS is actively open at a very early age, but
      the reported age of closure of the NCS varies from age 3 to 16 years. This
      various closure age of the NCS has resulted in some confusion about the role of
      the NCS in the normal spinal growth or the development of spinal deformity.
      METHODS: A total of 34 normal pediatric patients who had axial magnetic resonance
      images from first thoracic vertebra to fifth lumbar vertebra were assigned into
      following 3 groups: infantile group (n = 11), 0 to 3 years of age; juvenile-young
      group (n = 16), 4 to 7 years of age; and juvenile-old group (n = 7), 8 to 10
      years of age. T2-weighted axial magnetic resonance images were used to analyze
      the NCS developmental stages using a custom 6-point scale (0: actively open with
      0% closure; 5: 100% NCS closure). For the stage 0 closure NCS, the width and
      thickness of the NCS were measured. RESULTS: The NCS was actively open without
      closure for all less than 4-year-old patients at all levels. The NCS had
      approximate 75% closure in the lumbar region at 4 years of age while the thoracic
      NCS remained nearly open. After 5 years of age, the middle-lower thoracic NCS
      began to close with closure rate less than 25%. At the 10 years of age, the NCS
      in the lumbar region had near 100% closure, whereas the thoracic NCS demonstrated
      approximate 50% closure. For the NCS without closure, the average width and
      thickness were 7.6 x 1.3 mm on the left and 7.9 x 1.3 mm on the right, which was
      not significantly different. For the NCS with closure, the left and right NCS
      closure rates were not significantly different. CONCLUSION: The NCS developmental
      stage is age- and vertebral level-dependent. The NCS closes from the lumbar and
      proximal thoracic spine to the middle-distal thoracic spine and times from very
      early juvenile to the adolescent. The NCS symmetry bilaterally occurred not only
      during the active open, but also the long closure period. The NCS symmetric open
      and/or closure may be important to maintain the normal spine alignment.

PMID- 20042960
TI  - Complications of spinal fusion for scheuermann kyphosis: a report of the
      scoliosis research society morbidity and mortality committee.
AB  - STUDY DESIGN: Retrospective review of a prospectively collected, multicentered
      database from the Scoliosis Research Society. OBJECTIVES: To evaluate incidences
      of complications in a series of spinal fusions for Scheuermann kyphosis (SK) and
      to assess whether the incidence of complications is associated with patient age
      and surgical approach. SUMMARY OF BACKGROUND DATA: Although there is some
      evidence that adolescents have lower complication rates for spinal deformity
      surgery, this has not been well-documented for SK. Moreover, there is a lack of
      consensus on surgical approach for the management of SK. METHODS: The Scoliosis
      Research Society morbidity and mortality database was queried to identify cases
      of SK from 2001 to 2004. Complications rates were analyzed based on patient age
      and surgical approach. Pediatric and adult patients were defined as <or=19 and
      >19 year old, respectively. RESULTS: A total of 683 procedures involving spinal
      fusion for SK were identified. Mean patient age was 21 years (range: 5-75 years),
      with the majority (73%) of patients <or=19 years old. Procedures included 338
      (49%) posterior spinal fusions (PSF), 73 (11%) anterior spinal fusions (ASF), and
      272 (40%) same-day ASF and PSF. Ninety-nine complications were reported (14%).
      The most common complication was wound infection (3.8%). The acute neurologic
      complication rate was 1.9%, including 4 spinal cord injuries (0.6%). The
      mortality rate was 0.6%. Complications were more common among adult (22%)
      compared with pediatric patients (12%) (P = 0.002). The overall incidence of
      complications did not differ significantly between the PSF (14.8%) and same-day
      ASF/PSF (16.9%) procedures (P = 0.5). CONCLUSION: The incidence of complications
      associated with spinal fusion for SK in adults is significantly greater than in
      pediatric patients. There were no significant differences in complication rates
      between PSF and same-day ASF/PSF procedures. These data may be used to counsel
      patients regarding complications associated with spinal fusion for SK in the
      hands of experienced spinal deformity surgeons.

PMID- 20042961
TI  - Incidence of spinal and spinal cord injuries and their surgical treatment in
      children and adolescents: a population-based study.
AB  - STUDY DESIGN: A population based, epidemiological study. OBJECTIVE: To
      investigate incidence of spinal and spinal cord injuries and their surgical
      treatment in children and adolescents in Finland. SUMMARY OF BACKGROUND DATA:
      Epidemiological data on spinal injuries and their treatment in children is
      sparse. METHODS: All spinal and spinal cord injuries in children under 18 years
      of age treated in hospital between 1997 and 2006 in Finland were included. The
      data on injuries, hospitalizations, and surgical treatment were collected from
      the National Hospital Discharge Register which includes all in-patient treatment
      episodes. Fatal spinal injuries were derived from the Official Cause-of-Death
      Statistics of Finland. RESULTS: The overall incidence of spinal injuries remained
      stable during the follow-up period, averaging 66 per 10 of the reference
      population aged below 18 years. The proportions of cervical, thoracic, and lumbar
      spine injuries altered with age: 64% of spinal injuries in children below 8 years
      of age were cervical, while in the older children lumbar (42%) and thoracic spine
      injuries (33%) were more common than cervical. The incidence of spinal cord
      injuries averaged 1.9 per 10 children. Thirty percent of the children with spinal
      injury underwent surgery. The annual incidence of fatal spinal injury averaged
      2.4 per 10 children. CONCLUSION: Pediatric spinal and spinal cord injuries are
      rare. In contrast to previous literature, the most commonly affected area is
      lumbar spine. One-third of the children with spinal injury underwent surgery.

PMID- 20042962
TI  - In the eye of the beholder: preferences of patients, family physicians, and
      surgeons for lumbar spinal surgery.
AB  - STUDY DESIGN: Survey to all orthopedic and neurosurgeons, a random sample of
      family physicians (FPs) and patients in Ontario, Canada. OBJECTIVE: To identify
      the dominant clinical factors influencing patient and physician preferences for
      lumbar spinal surgery. SUMMARY OF BACKGROUND DATA: Surgery on the degenerative
      lumbar spine offers significant benefit for patients with moderate-severe
      symptoms failing nonoperative treatment. Referring FPs have little appreciation
      of factors that identify the ideal surgical candidate. Differences in preferences
      may lead to wide variation in referrals and impedes the shared decision-making
      process. METHODS: We used conjoint analysis, a rigorous method for eliciting
      preferences, to determine the importance that respondents place on decisions for
      lumbar spinal surgery. We identified 6 clinical factors (walking tolerance, pain
      duration, severity, neurologic symptoms, typical onset, and dominant location of
      pain) and presented hypothetical vignettes to participants who rated their
      preference for surgery. Data were analyzed using random-effects ordered probit
      regression models and the importance of each clinical factor relative to the
      others was determined. RESULTS: We obtained responses from 131 surgeons, 202 FPs,
      and 164 patients. We found that FPs had the highest overall preferences for
      surgery and surgeons had the lowest. Surgeons placed the highest importance on
      the location of pain. FPs considered neurologic symptoms, walking tolerance, and
      severity to be of similar importance. Pain severity, walking tolerance, and
      duration of pain were the most important factors for patients in deciding for
      surgery. Orthopedic (over neurosurgical) surgeons had a lower preference for
      surgery (P < 0.05). Older patients (P < 0.03) and previous surgical consultation
      (P < 0.03) had greater patient preferences for surgery. CONCLUSION: Different
      preferences for surgery exist between surgeons, FPs, and patients. FPs may reduce
      over- and under-referrals by appreciating surgeons' importance on location of
      pain (leg vs. back). Surgeons and FPs may improve the shared decision-making
      process by understanding that patients place high importance on quality of life
      symptoms.

PMID- 20042964
TI  - Surgery significantly improves survival in patients with chordoma.
AB  - STUDY DESIGN: Retrospective database review using Surveillance, Epidemiology, and
      End Results database, National Cancer Institute. OBJECTIVE: To determine current
      treatment outcomes and demographic characteristics and to define the prognostic
      factors and impact of surgery on survival. SUMMARY OF THE BACKGROUND DATA: Rarity
      of the disease has limited the number of population-based studies addressing the
      issues of prognostic factors and the current treatment outcomes. METHODS: A total
      of 962 patients with chordoma, diagnosed between 1973 and 2005, were identified
      in the Surveillance, Epidemiology, and End Results database. Patient demographics
      and clinical characteristics, incidence, year of diagnosis, location, size and
      stage at diagnosis, treatment(s), and survival were extracted. Kaplan-Meier, log
      rank, and Cox regression were used to analyze the significance of prognostic
      factors. RESULTS: Race specific incidence per 100,000 persons in 2005 shows
      whites to have the highest (0.473) incidence, followed by Asians/Pacific
      Islanders (0.091), and Afro-Americans (zero), respectively. The incidence
      difference between whites and Afro-Americans over time is statistically
      significant (P < 0.001). The age adjusted incidence reveals a peak in eighth
      decade of life. Survival was not impacted by race. Age category <59, Hispanic
      ethnicity, size <8 cm, and surgical resection were all independent predictors of
      better overall survival. Analysis revealed that survival outcomes were very
      similar in patients with "in-operable disease" and those in which "surgery was
      recommended but not performed" suggesting that benefits of resection cannot be
      solely attributed to selection bias. CONCLUSION: With high local recurrence rates
      and the significant functional morbidity associated with surgical resections,
      clinicians are left wondering if surgery constitutes an appropriate treatment
      option. Our study clearly demonstrates that surgery significantly improves the
      overall survival for patients with chordoma. We have further identified age <59
      and size of primary tumor <8 cm as important prognostic factors determining the
      outcome with substantial statistical significance.

PMID- 20042967
TI  - Re: Szalay EA, Bosch P, Schwend RM, et al. Adolescents with idiopathic scoliosis
      are not osteoporotic. Spine 2008;33:802-6.

PMID- 20042965
TI  - Instrumented one and two level posterolateral fusions with recombinant human bone
      morphogenetic protein-2 and allograft: a computed tomography study.
AB  - STUDY DESIGN: Prospective analysis of patients fused with freeze-dried
      corticancellous allograft, local bone graft, and recombinant human bone
      morphogenetic protein (rhBMP-2) (Infuse) studied for a minimum follow-up of 24
      months. OBJECTIVES: To assess the fusion rates of the allograft and Infuse using
      plain radiographs and reconstructed computed tomography (CT) scans. Outcome
      measures included Oswestry Disability Index, Verbal Rating Pain Scale for back
      and leg pain, and SF-36 Health Survey as well as complications. SUMMARY OF
      BACKGROUND DATA: The "gold standard" for arthrodesis of the lumbar spine includes
      the use of autogenous iliac crest bone graft. Morbidity associated with this
      harvest is well established. Alternatives to autogenous iliac crest bone graft
      harvest are being sought both to improve and match arthrodesis rate and
      secondarily to decrease donor site morbidity. METHODS: A prospective consecutive
      series of 36 patients treated for lumbar acquired spinal stenosis and
      degenerative disc disease leading to instrumented 1 and 2 level fusions were
      studied. These patients were arthrodesed with rhBMP-2 and freeze-dried
      corticancellous allograft and limited amounts of local autogenous bone graft.
      RESULTS: Fusion by reconstructed coronal and saggittal CT analysis occurred in
      97.2% of the cases. The Oswestry Disability Index, Verbal Rating Pain Scale, and
      SF-36 Health Survey were statistically improved (P < 0.05) from preoperative to
      final postoperative values. Complications were limited and unrelated to rhBMP-2
      and the absorbable collagen sponge. CONCLUSION: rhBMP-2 (Infuse) at a dose of 12
      mg/1.5 mg/mL combined with freeze-dried corticancellous allograft and local
      autogenous spinous process and lamina bone resulted in new bone formation
      (fusion) as determined by CT scan. In this preliminary study, fusion rates were
      97.2% with consistent posterolateral bone formation. Outcomes and complications
      are consistent with other studies of this type.

PMID- 20042968
TI  - Re: Myran R, Kvistad KA, Nygaard OP, et al. Magnetic resonance imaging assessment
      of the alar ligaments in whiplash injuries: a case-control study. Spine
      2008;33:2012-6.

PMID- 20042970
TI  - Age has no significant impact on overall survival and on treatment tolerability
      in relapsed stage IV cutaneous malignant melanoma patients receiving Cisplatin,
      Gemcitabine, and Treosulfan.
AB  - OBJECTIVES: We compared the efficacy and tolerability of cisplatin, gemcitabine,
      and treosulfan (CGT) therapy in younger patients (age, <60 years) and in elderly
      patients (age, >=60 years) with pretreated relapsed American Joint Committee on
      Cancer stage IV cutaneous malignant melanoma. PATIENTS AND METHODS: A total of 91
      patients at the age of 18 to 80 years, in relapse after first-, second-, or third
      line therapy received 40 mg/m intravenous (i.v.) cisplatin, 1000 mg/m i.v.
      gemcitabine, and 2500 mg/m i.v. treosulfan on days 1 and 8. CGT-therapy was
      repeated every 5 weeks until progression of disease occurred. RESULTS: Younger (n
      = 49) and elderly (n = 42) patients showed a significant difference in disease
      stabilization in 25% versus 7% (P <= 0.05), as opposed to 69% versus 91% patients
      exhibiting disease progression. In contrast, the overall median survival
      probability was not significantly different (P = 0.8153). Neither treatment
      related toxicity nor toxicity-associated dose reduction showed substantial
      differences. CONCLUSIONS: Our results demonstrated that CGT therapy could be
      safely administered to a patient up to age 80 years.

PMID- 20042969
TI  - Brain metastases from melanoma: is there a role for concurrent temozolomide in
      addition to whole brain radiation therapy?
AB  - OBJECTIVES: This study was performed to evaluate the addition of temozolomide
      (TMZ) to whole brain radiotherapy (WBRT) for brain metastases from melanoma.
      METHODS: Seven patients with brain metastases from melanoma were treated on a
      North Central Cancer Treatment Group (NCCTG) trial (N0274) of TMZ plus WBRT. TMZ
      was given orally in doses of 200 mg/m2 for 5 days every 4 weeks for up to 8
      cycles. WBRT was started on the first day of TMZ and included the delivery of
      3750 cGy in 15 fractions. In addition, separately analyzed was a cohort of 53
      patients treated at the Mayo Clinic who received WBRT alone (39 patients) or WBRT
      plus TMZ (14 patients). RESULTS: The median survival of the 7 patients treated on
      N0274 was 3.6 months with 2 of 7 (29%) failing in brain and 5 of 7 (71%) failing
      elsewhere. For the other cohort of 53 patients, the median survival was 3.8
      months with WBRT alone compared 4.3 months for WBRT plus TMZ (P = 0.5).
      CONCLUSIONS: Patients did not appear to benefit from the addition of TMZ to WBRT
      for the treatment of their brain metastases. Further improvements in outcome will
      require research to discover more effective systemic therapy and RT techniques.

PMID- 20042971
TI  - A phase II study of irinotecan, continuous 5-fluorouracil, and leucovorin
      (FOLFIRI) combination chemotherapy for patients with recurrent or metastatic
      gastric cancer previously treated with a fluoropyrimidine-based regimen.
AB  - OBJECTIVES: A phase II study was carried out to assess the efficacy and toxicity
      of combination chemotherapy with irinotecan, 5-fluorouracil (5-FU), and
      leucovorin (FOLFIRI) for the treatment of patients with metastatic or recurring
      gastric cancer previously treated with fluoropyrimidine-based chemotherapy.
      METHODS: Eligible patients were those who had metastatic gastric cancer
      previously treated with a fluoropyrimidine-based chemotherapy regimen or had
      disease recurrence within 6 months of completing adjuvant fluoropyrimidine
      containing chemotherapy. Participants received irinotecan (150 mg/m2 on day 1)
      and leucovorin (LV; 20 mg/m2 on days 1-2) followed by continuous infusion of 5-FU
      (1500 mg/m2 on days 1-2), every 2 weeks. RESULTS: Between April 2006 and March
      2008, 33 patients were enrolled in the study. FOLFIRI served as a second-line
      treatment in 27 patients, third-line treatment in 4 patients, and fourth-line
      treatment in 2 patients. The patients had a median age of 60 years (range, 40-75)
      and underwent 132 cycles of chemotherapy, with a median of 3 cycles (range, 1-15)
      per patient. The response rate was 18.2%, and the disease control rate was 36%.
      Median overall survival was 5.1 months (95% confidence interval, 3.74-6.45), and
      median time to progression was 2.3 months (95% confidence interval, 1.81-2.78).
      The major grade 3-4 toxicity was neutropenia (45.4%). CONCLUSION: Combination
      chemotherapy with irinotecan, 5-FU, and LV is feasible in gastric cancer patients
      previously treated with fluoropyrimidine-based chemotherapy.

PMID- 20042972
TI  - Phase II trial of dose dense docetaxel followed by FEC100 as neoadjuvant
      chemotherapy in patients with operable breast cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy and safety profile
      of 4 dose-dense cycles of docetaxel followed by 3 cycles of FEC100 neoadjuvant
      chemotherapy in patients with operable advanced breast cancer. METHODS: Women
      were treated by 4 cycles of 100 mg/m2 docetaxel every 2 weeks, followed by 3
      cycles of FEC100 given every 3 weeks. The primary end point was pathologic
      complete response. RESULTS: Forty-five patients were treated. Ninety-three
      percent of the patients completed the planned 7 chemotherapy courses. The median
      relative dose intensity for docetaxel, 5-fluorouracil, epirubicin, and
      cyclophosphamide were 0.98, 0.97, 0.96, and 0.97, respectively. There were no
      therapy-related deaths. Two patients stopped chemotherapy because of cutaneous
      toxicity. During the docetaxel sequence, the most common grade 3-4 toxicities
      were (% pts): neutropenia (13.3), grade 3: cutaneous (24.4), myalgia and
      arthralgia (6.7). No clinical cardiac toxicity was observed. The pathologic
      complete response rate was 21.4% and 26.2% using Sataloff and Chevallier
      classifications, respectively. The conservative surgery rate was 62.2%. The
      median follow-up was 38.5 months. Two and 3-year disease-free survival rates were
      79% and 64%, respectively. Two- and 3-year overall survival rate were 93% and
      88%, respectively. CONCLUSIONS: This trial confirms the feasibility and efficacy
      of this dose dense docetaxel neoadjuvant regimen.

PMID- 20042973
TI  - A multicenter phase II clinical trial of lapatinib (GW572016) in hormonally
      untreated advanced prostate cancer.
AB  - OBJECTIVES: Lapatinib (GW572016) is a selective and potent dual tyrosine kinase
      inhibitor of the epidermal growth factor 1 (EGFR) and 2 (HER2), approved in the
      treatment of HER2 positive breast cancer. Since EGFR and HER2 overexpression has
      also been seen in prostate cancer and appears to correlate with a worse clinical
      outcome, Lapatinib may represent a novel therapeutic strategy in prostate cancer.
      This Phase II multicenter clinical trial is the first to evaluate Lapatinib in
      early stage, hormonally untreated recurrent or metastatic prostate cancer.
      METHODS: Eligible patients received lapatinib 1500 mg PO daily until progression.
      The primary end point was prostate specific antigen (PSA) response. Archival
      tumor tissue was collected for EGFR and HER2 analysis. RESULTS: A total of 23
      patients, median age 67, ECOG PS 0-2, mean baseline PSA 7.5, were evaluable for
      response. In total, 125 cycles were administered. The most frequent adverse
      events were lymphopenia, fatigue, rash, dyspepsia, and diarrhea. Grade 3+
      increased alanine aminotransferase (ALT) was reported in 2 patients, and grade 4
      blurry vision in 1 patient. No PSA responses were seen. Median time to
      progression (TTP) was 4.6 months and 6 months progression-free estimate was
      44.5%. CONCLUSIONS: Lapatinib was well tolerated but like other EGFR- and HER2
      targeted agents in advanced HRPC failed to show significant antitumor activity
      even in this very early stage hormonally untreated population.

PMID- 20042974
TI  - Management of the airway in multitrauma.
AB  - PURPOSE OF REVIEW: The primary purpose of this article is to highlight the latest
      airway research in multitrauma. RECENT FINDINGS: Management of the airway in
      multitrauma patients is a critical resuscitation task. Prehospital airway
      management is difficult with a high risk of failure, complications, or both. In
      hospital performed conventional oral intubation with manual in-line
      stabilization, cricoid pressure, and a backup plan for a surgical airway is still
      the most efficient and effective approach for early airway control in multitrauma
      patients. Selective utilization of airway maintenance, instead of ultimate airway
      control in the field, has been suggested as a primary prehospital strategy.
      Properties of videolaryngoscopes complement standard laryngoscopes. When compared
      with a Macintosh laryngoscope, the Airtraq and Airwayscope diminish cervical
      spine motion during elective orotracheal intubation. Penetrating neck injuries
      are the most frequent indication for awake intubation, whereas patients with
      maxillofacial injuries have the highest rate of initial surgical airway. SUMMARY:
      Risks and benefits of ultimate prehospital airway control is a controversial
      topic. Utilization of videolaryngoscopes in multitrauma remains open for
      research. Standardization of training requirements, equipment, and development of
      prehospital and in-hospital airway algorithms are needed to improve outcomes.
      Rational utilization of available airway devices, development of new devices, or
      both may help to promote this goal.

PMID- 20042975
TI  - Demodex and skin infection: fact or fiction.

PMID- 20042976
TI  - Can we slow the progression of chronic kidney disease?
AB  - PURPOSE OF REVIEW: Childhood chronic kidney disease usually progresses towards
      end-stage renal failure once a critical impairment of renal function has
      occurred. This process is largely independent of the underlying renal disease.
      Recent clinical trials have provided evidence that the progressive course of
      chronic kidney disease can be slowed substantially by pharmacological
      intervention. RECENT FINDINGS: Hypertension and proteinuria are the most
      important independent risk factors for renal disease progression in both adult
      and pediatric nephropathies. Pharmacological blockade of the renin-angiotensin
      system provides efficient control of blood pressure and proteinuria, and superior
      long-term renoprotection compared with other antihypertensive agents. Recent
      pediatric evidence supports the renoprotective efficacy of tight blood pressure
      control aiming for the low-normal range. In addition, promising preliminary
      findings suggest an additional renoprotective potential by correction of
      metabolic acidosis and hyperuricemia and by administration of antiproliferative
      and antioxidative drugs. SUMMARY: Pharmacological renoprotection currently
      focuses on antihypertensive and antiproteinuric treatment by blockade of the
      renin-angiotensin system. Intensified blood pressure control can improve 5-year
      renal survival by 35% in children with chronic kidney disease. Additional
      complementary strategies under current clinical evaluation bear potential to
      improve renal survival even further.

PMID- 20042977
TI  - Coexisting chronic obstructive pulmonary disease and heart failure: implications
      for treatment, course and mortality.
AB  - PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) and heart failure
      are prevalent comorbidities affecting a huge proportion of the world population,
      responsible for significant morbidity and mortality. Their coexistence is more
      frequent than previously recognized and poses important diagnostic and
      therapeutic challenges. Prognosis of patients with concurrent heart failure and
      COPD has not been comprehensively addressed. With this review, we intend to
      emphasize the diagnosis and prognosis implications of the two coexisting
      conditions and to highlight the therapeutic constraints posed by the combination.
      RECENT FINDINGS: Progressively, more attention has been given to the interplay
      between COPD and heart failure. The combination is frequent, but largely
      unrecognized due to overlapping clinical manifestations. Patients presenting with
      both conditions seem to have an ominous course. Despite the overwhelming evidence
      supporting cardioselective beta-blockade safety and tolerability in COPD
      patients, beta-blockers are underprescribed to heart failure patients with
      concomitant COPD. SUMMARY: COPD and heart failure coexistence is often
      overlooked. COPD diagnosis can remain unsuspected in heart failure patients due
      to similar symptoms. Although beta-blockers are well tolerated in COPD patients,
      they are overall less prescribed in this challenging population. COPD, at least
      at severe degrees of airflow obstruction, predicts a worse prognosis in heart
      failure patients.

PMID- 20042978
TI  - Robot-assisted radical prostatectomy: advances since 2005.
AB  - PURPOSE OF REVIEW: To provide an update of recent studies relevant to robot
      assisted radical prostatectomy, highlighting technical modifications and
      associated functional outcomes, mid-term oncologic results and patient perception
      and satisfaction. RECENT FINDINGS: Several recent studies have investigated
      methods of further reducing the morbidities associated with prostatectomy, namely
      erectile dysfunction and incontinence. These studies provide important anatomic
      insights into additional mechanisms responsible for potency and incontinence and
      measures for preserving both. Mid-term oncologic outcomes have also been
      reported; further substantiating the role of robotics in the treatment of
      clinically localized prostate cancer. SUMMARY: The technique of robotic
      prostatectomy has evolved over the last decade with significant efforts in
      improving functional outcomes following surgery. However, aggressive-marketing
      campaigns and lack of regulation of hospital websites may be contributing to
      unrealistic expectations in patients who choose to undergo robotic prostatectomy,
      resulting in dissatisfaction for some patients. National interests in this topic
      will likely result in the mandate for more stringent studies to assess the
      comparative effectiveness of robot-assisted prostatectomy with other competing
      therapies for clinically localized prostate cancer.

PMID- 20042979
TI  - Force exertion capacity measurements in haptic virtual environments.
AB  - An objective test for evaluating functional status of the upper limbs (ULs) in
      patients with muscular distrophy (MD) is presented. The method allows for
      quantitative assessment of the UL functional state with an emphasis on force
      exertion capacity. The experimental measurement setup and the methodology for the
      assessment of maximal exertable force utilizing the Phantom 1.5 haptic interface
      has been developed. The measurement setup consists of a powerful virtual reality
      simulator, capable of providing haptic, visual and audio feedback. The patient's
      task in the virtual environment is goal oriented and includes stretching a
      virtual spring in six different directions. The Phantom 1.5 haptic interface
      serves as a kinematic measuring device and as a force feedback generator. By
      moving the haptic interface control stick the patient exerts the force in six
      radial directions to the best of his or her abilities. The new test offers
      numerical as well as graphic results. The method has been applied to 32 MD
      patients. Several typical force exertion capacity characteristics, affected by
      neuro-muscular disorders are shown in a quantitative manner. Data mining was used
      to demonstrate good content validity of the proposed test. The method allows for
      a quick, accurate, repeatable and objective measurements of the UL force exertion
      capability.

PMID- 20042980
TI  - Outcome assessment in traumatic brain injury clinical trials and prognostic
      studies.
AB  - Large numbers of investigations have sought to evaluate prediction of outcome
      after traumatic brain injury (TBI) and the effectiveness of interventions
      designed to address post-TBI deficits. Unfortunately, failure to attend to key
      issues in experimental design regarding outcome assessment has limited the
      utility of these investigations. Increased attention to 5 issues in outcome
      assessment will increase the evidence base for TBI prognosis and treatment and
      increase the relevance of findings to end users of research such as other
      investigators, rehabilitation providers, policy makers, persons with TBI, and
      family members of persons with TBI. These 5 issues are (1) masking of outcome
      examiners, (2) retention of study participants, (3) use of surrogate informants
      to capture data from a wider range of study participants, (4) relevance of study
      outcomes to stakeholders, and (5) cultural considerations in outcome assessment.

PMID- 20042981
TI  - Participant-proxy agreement on objective and subjective aspects of societal
      participation following traumatic brain injury.
AB  - OBJECTIVE: To examine congruence between participant (P) and significant other
      (SO) reports on societal participation in 3 objective domains (economic,
      community, and social activities) and subjective satisfaction with participation
      at 1 year after traumatic brain injury (TBI). PARTICIPANTS: Ninety-seven persons
      with moderate to severe TBI and their SOs (27 spouses/partners, 47 parents, 23
      other relatives/friends). MAIN OUTCOME MEASURE: Community Participation
      Indicators questionnaire, divided into Objective (Economic, Community, Social)
      and Subjective (Satisfaction) subscales. DESIGN: Prospective correlational study.
      RESULTS: P-SO congruence differed by domain of participation, with Economic and
      Community indicators showing higher agreement than Social and Satisfaction items.
      Congruence was not affected by P-SO relationship or whether the pair lived
      together. However, pairs who spent at least daily time together had significantly
      higher agreement on Satisfaction items than pairs who were together less often.
      Congruence was not predicted by SOs' self-reported degree of awareness of Ps'
      concerns. Severity of TBI, within the range represented in this sample, had no
      effect on P-SO congruence in any domain. CONCLUSION: In research on participation
      after TBI, proxy report may be an acceptable substitute for missing participant
      report on productivity and community activity outcomes. However, proxy responses
      should be used with caution for questions about social activities and degree of
      satisfaction with participation.

PMID- 20042982
TI  - Traumatic brain injury, posttraumatic stress disorder, and postconcussive symptom
      reporting among troops returning from iraq.
AB  - OBJECTIVES: Analyze the contribution of mild traumatic brain injury (mTBI) and/or
      posttraumatic stress disorder (PTSD) to the endorsement of postconcussive (PC)
      symptoms during Post Deployment Health Assessment. Determine whether a
      combination of mTBI and PTSD was more strongly associated with symptoms than
      either condition alone. METHODS: Cross-sectional study design where both the
      exposure, mTBI and/or PTSD, and the outcomes of interest, PC symptoms, were
      ascertained after return from deployment. Subjects were injured soldiers (n =
      1247) from one Fort Carson Brigade Combat Team (n = 3973). MAIN OUTCOME MEASURES:
      Positive history of PC symptoms. RESULTS: PTSD and mTBI together were more
      strongly associated with having PC symptoms (adjusted prevalence ratio 6.27; 95%
      CI: 4.13-9.43) than either mTBI alone (adjusted prevalence ratio = 4.03; 95% CI:
      2.67-6.07) or PTSD alone (adjusted prevalence ratio = 2.74; 95% CI: 1.58-4.74)
      after adjusting for age, gender, education, rank, and Military Occupational
      Specialty. CONCLUSIONS: In soldiers with histories of physical injury, mTBI and
      PTSD were independently associated with PC symptom reporting. Those with both
      conditions were at greater risk for PC symptoms than those with either PTSD,
      mTBI, or neither. Findings support the importance of continued screening for both
      conditions with the aim of early identification and intervention.

PMID- 20042983
TI  - Predictors of psychiatric disorders following traumatic brain injury.
AB  - OBJECTIVE: To investigate predictors of posttraumatic brain injury psychiatric
      disorders. DESIGN: Retrospective, cross-sectional design with stratified random
      sampling of groups of patients on average 1 to 5 years postinjury. DSM-based
      diagnostic interviews of both traumatic brain injury (TBI) participant and
      informant. PARTICIPANTS: One hundred community-based participants, aged 19-74
      years, with traumatic brain injury sustained 0.05-5.5 years previously. SETTING:
      Community-based patients previously treated at a rehabilitation hospital. MAIN
      MEASURE: The Structured Clinical Interview for DSM-IV diagnosis. RESULTS: A
      psychiatric history was a high-risk factor for having the same disorder
      postinjury. However, the majority of cases of depression and anxiety were novel,
      suggesting that significant factors other than pre-TBI psychiatric status
      contribute to post-TBI psychiatric outcome. Female gender, lower education, and
      pain were also associated with postinjury depression and unemployment and older
      age with anxiety. CONCLUSION: Findings suggest that long-term screening and
      support are important for individuals with TBI, regardless of preinjury
      psychiatric status.

PMID- 20042984
TI  - Reducing macrophages to improve bone marrow stromal cell survival in the contused
      spinal cord.
AB  - We tested whether reducing macrophage infiltration would improve the survival of
      allogeneic bone marrow stromal cells (BMSC) transplanted in the contused adult
      rat thoracic spinal cord. Treatment with cyclosporine, minocycline, or
      methylprednisolone all resulted in a significant decrease in macrophage
      infiltration at 3 days postinjury. However, when BMSC were injected at that time
      point, survival 7 days later was similar between treatment groups and saline
      injected controls. In fact, we found that the presence of BMSC resulted in a
      significant increase in macrophage infiltration into the contusion.

PMID- 20042985
TI  - Red blood cell transfusion is associated with infection and extracerebral
      complications after subarachnoid hemorrhage.
AB  - OBJECTIVE: Red blood cell transfusion (RBCT) is associated with medical
      complications in general medical and surgical patients. We examined the
      hypothesis that RBCT during intensive care unit (ICU) care is associated with
      medical complications after subarachnoid hemorrhage (SAH). METHODS: We
      retrospectively analyzed a prospective observational database containing 421
      patients with SAH (mean age, 51.5 years; standard deviation, 14.6 years).
      Logistic regression models were used to adjust for age, admission hemoglobin
      (Hgb), clinical grade, average ICU Hgb, and symptomatic vasospasm. RESULTS: Two
      hundred fourteen patients received an RBCT during their ICU stay. Medical
      complications were identified in 156 patients and were more common in those who
      received blood (46%) than in those who did not (29.8%) (P < .001). Major medical
      complications (cardiac, pulmonary, renal, or hepatic) occurred in 111 patients,
      and minor complications (eg, skin rash, deep vein thrombosis) occurred in 45
      patients. Any non-central nervous system infection (n = 183; P < .001), including
      pneumonia (n = 103; P < .001) or septicemia (n = 36; P = .02), was more common
      with RBCT. Central nervous system infections (meningitis, cranial wound, n = 15)
      also were associated with RBCT (P = .03). Mechanically ventilated patients (n =
      259) were more likely to have received an RBCT than those who did not (P < .001).
      When logistic regression was used to control for age, admission clinical grade
      and Hgb, average ICU Hgb, symptomatic vasospasm, and other admission variables
      associated with outcome, the following factors (odds ratio; 95% confidence
      interval) were associated with RBCT: any medical complication (1.8; 1.1-3.0),
      major medical complications (2.1; 1.2-3.7), any infection (2.8; 1.7-4.5),
      pneumonia (2.6; 1.5-4.7), septicemia (2.9; 1.2-6.8), and need for mechanical
      ventilation (2.8; 1.5-5.1). CONCLUSION: These data suggest that RBCTs are
      associated with medical complications after SAH. However, the data do not infer
      causation, and further study is necessary to better define the indications for
      transfusion after SAH.

PMID- 20042986
TI  - Bone morphogenetic proteins and cancer: review of the literature.
AB  - OBJECTIVE: In addition to their well-known osteogenic properties, bone
      morphogenetic proteins (BMPs) have developmental and regenerative roles that may
      impact tumorigenesis and promote tumor spread. Given that the most common site of
      tumor metastases to bone is the spine, determining whether BMPs can be linked to
      cancer is of particular relevance to surgeons treating primary or metastatic
      spinal disease. This article reviews the basic scientific and clinical background
      of BMPs and their potential role in promoting cancer. METHODS: A literature
      review to identify studies relating to BMP and tumorigenesis was conducted.
      Databases evaluated included MEDLINE and EMBASE as well as the Cochrane
      Controlled Trials Register through 2008. RESULTS: Bone morphogenetic proteins are
      a diverse class of molecules belonging to the transforming growth factor-beta
      superfamily that serve a variety of biologic functions. Bone morphogenetic
      proteins have critical roles in stem and progenitor cell biology as regulators of
      cellular expansion and differentiation. Transforming growth factor-beta and
      related cell signaling pathways as well as stem and progenitor cell signaling
      have been linked to cancer. Multiple in vitro and in vivo studies suggest a
      significant role of BMPs in promoting tumorigenesis and metastasis. However,
      there are also comparable studies that imply that BMPs may have a negative effect
      on cancer. CONCLUSION: There is no definitive association between BMPs and the
      promotion of tumorigenesis or metastasis. However, given the relatively large
      number of studies reporting a positive effect of BMPs on tumorigenesis or
      metastasis, the use of BMPs in patients with primary or metastatic spinal tumors
      should be carefully considered.

PMID- 20042987
TI  - Supracerebellar infratentorial approach to cavernous malformations of the
      brainstem: surgical variants and clinical experience with 45 patients.
AB  - OBJECTIVE: The supracerebellar infratentorial (SCIT) approach can be performed at
      the midline (median variant), lateral to the midline (paramedian variant), or at
      the level of the angle formed by the transverse and sigmoid sinuses (extreme
      lateral variant). We analyzed our experience with SCIT approaches for the
      surgical treatment of cavernous malformations of the brainstem (CMBs). METHODS:
      Demographic, clinical, radiologic, and surgical data from 45 patients (20 males
      and 25 females; mean age, 36.2 years) with CMBs surgically removed through SCIT
      approaches were reviewed retrospectively. Anatomic information was explored using
      cadaver head dissection. RESULTS: Twenty-three lesions were in the midbrain, 3
      were at the midbrain and extended to the thalamus, 9 were at the
      pontomesencephalic junction, and 10 were in the upper pons. All patients
      presented with hemorrhage. The median variant was used in 13 patients, the
      paramedian variant in 9, and the extreme lateral variant in 23. Intraoperatively,
      all CMBs were associated with a developmental venous anomaly. At last follow-up,
      88% of the patients were the same or better. After a mean follow-up of 20 months,
      their mean Glasgow Outcome Scale score was 4.1. CONCLUSION: SCIT approaches
      provide excellent exposure to CMBs located at the posterior incisural space, not
      only in the midline but also in the posterolateral surface of the upper pons and
      midbrain. Careful preoperative planning and neuronavigational assistance are
      needed to determine the best angle of attack and trajectory for SCIT approaches.
      Refined microsurgical techniques are paramount to achieve safe surgical removal
      of CMBs with good outcomes.

PMID- 20042988
TI  - Long-term outcome of total and near-total resection of spinal cord lipomas and
      radical reconstruction of the neural placode, part II: outcome analysis and
      preoperative profiling.
AB  - OBJECTIVE: To show the long-term benefits of total and near-total resection of
      complex spinal cord lipomas and reconstruction of the neural placode. METHODS: We
      analyzed 238 patients with dorsal, transitional, and chaotic lipomas who had
      total resection as described in part I for overall progression-free survival
      probability (PFS, Kaplan-Meier analysis) over 16 years. We also analyzed subgroup
      proportional recurrence hazard (Cox analysis) of 6 outcome predictors of sex,
      lipoma type, age, preoperative symptoms, previous surgery, and postoperative cord
      sac ratio. These results were compared with an age-matched, lesion-matched series
      of 116 patients followed for 11 years after partial lipoma resection and with the
      Parisian series of nonsurgical treatment. RESULTS: The immediate effects of
      surgery were similar between total and partial resection: both achieved greater
      than 95% symptom stabilization or improvement rate. The neuro-urologic
      complication rates for the groups were also similar, 4.2% and 5.2% for total and
      partial resection, respectively. The combined cerebrospinal fluid leakage and
      wound complication rate of total resection was much lower at 2.5% than the 6.9%
      for partial resection, but both were better than published rates. The overall PFS
      for total resection was 82.8% at 16 years, comparing much more favorably with
      34.6% for partial resection at 10.5 years (P < .0001). Culling only the
      asymptomatic patients with virgin (previously unoperated) lipomas to match the
      patient profile of the Parisian series, the PFS for prophylactic total resection
      for this subgroup increased to 98.4% at 16 years, versus 67% at 9 years for no
      surgery and 43.3% at 10.5 years for our own partial resection series, with a
      remarkable statistical difference between total and partial resection (P =
      .00001). Subgroup analyses showed that sex and lipoma type did not affect
      outcome. For the other predictor variables, while univariate analyses showed that
      young age, absence of symptom, and virgin lipomas correlated with better
      statistical PFS than older age, symptoms, and redo lipomas, these effects
      vanished with multivariate analyses. Cord-sac ratio stood alone as the only
      influential outcome predictor in multivariate analysis, with a 96.6% PFS for a
      low ratio of <30% and an 80.6% progression-free probability for a high ratio of
      >50%, and a 3-fold increase in recurrence hazard for high ratios (P = .0009).
      This suggested that all the individual effects of the other predictor variables
      could be reduced to whether a low cord-sac ratio could be achieved with total
      lipoma resection and placode reconstruction. Cord-sac ratio was the obvious
      factor that differentiated the outcomes between total and partial resection, the
      latter associated with a >90% chance of having a high cord-sac ratio. CONCLUSION:
      Total and near-total resection of lipomas and complete reconstruction of the
      neural placode produced a much better long-term progression-free probability than
      partial resection and nonsurgical treatment. The perioperative complications for
      total resection were low and compared favorably with published results. A low
      postoperative cord-sac ratio and well-executed placode neurulation were strongly
      correlated with good outcome. The ideal preoperative patient profile with early
      disease stabilization and the best recurrence-free probability is an asymptomatic
      child less than 2 years without previous lipoma surgery. There are strong
      indications that partial resection in many cases produces worse scarring on the
      neural placode and worse prognosis than no surgery.

PMID- 20042989
TI  - Comparative utility of gated myocardial perfusion imaging and transthoracic
      coronary flow reserve for the assessment of coronary artery disease in patients
      with left bundle branch block.
AB  - OBJECTIVES: To compare the diagnostic utility of gated single-photon emission
      computed tomography (SPECT) methoxy isobutyl isonitrile (MIBI) myocardial
      perfusion imaging and transthoracic Doppler echocardiography (TTDE) coronary flow
      reserve (CFR) to coronary angiography for detecting coronary artery disease (CAD)
      in patients with left bundle branch block (LBBB). METHOD: Forty-three patients
      with complete LBBB and an intermediate pretest probability for CAD underwent
      dipyridamole stress TTDE and gated SPECT MIBI during the same session and
      coronary angiography within a month. The parameters of myocardial perfusion
      (summed stress score, summed difference scores) regional wall function (wall
      motion score, wall thickening score) and ejection fraction were derived using the
      17-segment model and 4D-MSPECT software. TTDE variables included peak flow
      velocity at rest and during hyperemia in left anterior descending artery (LAD),
      based on which CFR was calculated (normal>2). RESULTS: Perfusion ischemic scores
      were significantly higher in group 1 with angiographic evidence of greater than
      50% LAD stenosis compared with group 2 with less than 50% LAD stenosis (summed
      stress score 12.4+/-5.5 vs. 8.3+/-3.5, P<0.05, summed difference score 3.7+/-1.2
      vs. 1.1+/-0.3, P<0.01, respectively). Left ventricular regional wall function and
      ejection fraction were not different between the two groups. CFR was
      significantly lower in group 1 than in group 2 (1.65+/-0.21 vs. 2.31+/-0.28,
      P<0.001). Gated SPECT MIBI and CFR had similar sensitivity (88 vs. 88%),
      specificity (80 vs. 84%), and accuracy (84 vs. 86%) for detecting CAD in patients
      with LBBB. The agreement between the two methods was 85%. CONCLUSION: Our results
      show comparable diagnostic utility and high agreement between gated SPECT MIBI
      perfusion imaging and TTDE CFR assessment for detecting CAD in patients with
      LBBB. The advantage of gated SPECT MIBI over TTDE CFR measurements is the ability
      to assess the perfusion abnormalities in multiple vascular territories during the
      same procedure, which is convenient for detecting multi-vessel disease in
      patients with LBBB.

PMID- 20042990
TI  - Round window surgery.

PMID- 20042991
TI  - Pediatric malignant peripheral nerve sheath tumor in auricula.

PMID- 20042992
TI  - Type III tympanoplasty with titanium total ossicular replacement prosthesis:
      anatomic and functional results.
AB  - OBJECTIVE: To evaluate anatomical and functional results using titanium
      prostheses in cartilage palisade tympanoplasties. STUDY DESIGN: Retrospective
      clinical study. Data were collected from patients' charts and clinical review.
      SETTING: Tertiary referral center. INTERVENTION: Cartilage tympanoplasty with
      titanium total ossicular replacement prosthesis after tympanoplasty or
      tympanomastoidectomy in patients operated on between July 1998 and February 2006.
      MAIN OUTCOME MEASURES: Anatomical results (closure of the perforation, rate of
      retraction pockets, recurrent cholesteatoma, and extrusion and re-perforation
      rates) were clinically evaluated. Pure-tone averages of air and bone conduction
      were analyzed. A postoperative air-bone gap (ABG) of 20 dB or less was taken to
      represent successful hearing.The hearing outcomes of canal wall up (CWU), canal
      wall down (CWD), primary and revision surgeries, and 2 groups of a short-term
      (<12 mo) or long-term (>24 mo) follow-up (f-u) were assessed and compared.
      RESULTS: Ninety-four cases were observed during the visiting period: 43 (45.7%)
      underwent primary procedures and 51 (54.3%) underwent revision surgeries. Closure
      of the tympanic membrane was achieved in 98.9%.Postoperative ABG was 20 dB or
      lower in 62 (66%) of 93 cases, between 11 and 20 dB in 33 cases (35%), and 10 dB
      or lower in 29 cases (31%).All cases undergoing CWU had a mean +/- SD
      postoperative ABG of 14.59 +/- 11.28 dB. There were no statistically significant
      differences (independent-samples t test, p = 0.5) between these patients and
      those receiving CWD surgery (15.95 +/- 10 dB).Thirty-eight (68%) of 56 CWD and 24
      (64%) of 37 CWU cases achieved a postoperative ABG between 0 and 20 dB (chi =
      0.08, p = 0.7, correlation = 0.031).Thirty-three (64.7%) of 51 who underwent
      revision surgeries and 29 (69%) of 42 who underwent primary procedures had a
      postoperative ABG between 0 and 20 dB. The difference between the groups was not
      significant (chi = 0.3, correlation = 0.058, p = 0.5).The mean ABG in the short f
      u group was 12.38 +/- 7.34. There was no significant difference regarding long
      term f-u after 24 months (11.76 +/- 8.9; Wilcoxon signed-rank test, p = 0.7).We
      compared the mean postoperative ABG in low hearing frequencies (500 and 1,000 Hz)
      and high hearing frequencies (2,000 and 4,000 Hz). A better sound transmission
      was achieved in high frequencies (10.32 +/- 10.6 versus 20.61 +/- 13.73 dB,
      respectively); the difference was statistically significant (p < 0.001, paired
      samples t test). CONCLUSION: Our results suggest that tympanoplasty with titanium
      total ossicular replacement prosthesis reconstruction offers a stable improvement
      of the ABG less than 20 dB in 66% of cases, in both short-term and long-term f-u.
      There were no differences in the results between CWU and CWD or between primary
      and revision surgery. The titanium prosthesis achieves the best acoustical
      results for sound transmission at high frequencies (2,000 and 4,000 Hz).

PMID- 20042993
TI  - Objective method of assessing and presenting the House-Brackmann and regional
      grades of facial palsy by production of a facogram.
AB  - OBJECTIVE: To produce a reliable objective method of assessing the House
      Brackmann (H-B) and regional grades of facial palsy with the results produced and
      presented in a time and manner suitable for a routine clinical setting. STUDY
      DESIGN: Analysis of video pixel data using artificial neural networks (ANNs).
      SETTING: Tertiary-referral neuro-otologic center. SUBJECTS: Subjects with varying
      degrees of unilateral facial palsy. METHOD: Clinicians assessed videos of
      subjects with varying degrees of facial palsy performing prescribed movements.
      The results of their overall and regional assessments were used to train ANNs.
      These were then tested for consistency, accuracy, and ability to identify
      clinical changes in grading. RESULTS: A group of subjects had their objective
      computer assessment repeated, and consistent H-B and regional grades were
      obtained. A second group had both subjective clinical and objective computer
      assessments performed. The program gave results that were within the expected
      level of agreement with the subjective clinical assessment for both H-B and
      regional grades. A third group had repeated clinical and computer assessments
      from the time of onset to recovery of facial function. The changes in the
      computer results both for H-B and regional grades tracked the clinical change.
      CONCLUSION: It is possible to measure consistently and objectively the H-B and
      regional grades of facial palsy using trained ANNs to analysis video pixel data,
      and this can be done in a routine clinical environment by a technician. The
      results from each region of the face are presented as a Facogram along with the H
      B grade.

PMID- 20042997
TI  - A practical approach to genetic inducible fate mapping: a visual guide to mark
      and track cells in vivo.
AB  - Fate maps are generated by marking and tracking cells in vivo to determine how
      progenitors contribute to specific structures and cell types in developing and
      adult tissue. An advance in this concept is Genetic Inducible Fate Mapping
      (GIFM), linking gene expression, cell fate, and cell behaviors in vivo, to create
      fate maps based on genetic lineage. GIFM exploits X-CreER lines where X is a gene
      or set of gene regulatory elements that confers spatial expression of a modified
      bacteriophage protein, Cre recombinase (CreER(T)). CreER(T) contains a modified
      estrogen receptor ligand binding domain which renders CreER(T) sequestered in the
      cytoplasm in the absence of the drug tamoxifen. The binding of tamoxifen releases
      CreER(T), which translocates to the nucleus and mediates recombination between
      DNA sequences flanked by loxP sites. In GIFM, recombination typically occurs
      between a loxP flanked Stop cassette preceding a reporter gene such as GFP. Mice
      are bred to contain either a region- or cell type-specific CreER and a
      conditional reporter allele. Untreated mice will not have marking because the
      Stop cassette in the reporter prevents further transcription of the reporter
      gene. We administer tamoxifen by oral gavage to timed-pregnant females, which
      provides temporal control of CreER(T) release and subsequent translocation to the
      nucleus removing the Stop cassette from the reporter. Following recombination,
      the reporter allele is constitutively and heritably expressed. This series of
      events marks cells such that their genetic history is indelibly recorded. The
      recombined reporter thus serves as a high fidelity genetic lineage tracer that,
      once on, is uncoupled from the gene expression initially used to drive CreER(T).
      We apply GIFM in mouse to study normal development and ascertain the contribution
      of genetic lineages to adult cell types and tissues. We also use GIFM to follow
      cells on mutant genetic backgrounds to better understand complex phenotypes that
      mimic salient features of human genetic disorders. This video article guides
      researchers through experimental methods to successfully apply GIFM. We
      demonstrate the method using our well characterized Wnt1-CreER(T);mGFP mice by
      administering tamoxifen at embryonic day (E)8.5 via oral gavage followed by
      dissection at E12.5 and analysis by epifluorescence stereomicroscopy. We also
      demonstrate how to micro-dissect fate mapped domains for explant preparation or
      FACS analysis and dissect adult fate-mapped brains for whole mount fluorescent
      imaging. Collectively, these procedures allow researchers to address critical
      questions in developmental biology and disease models.

PMID- 20042998
TI  - Commonly used surrogates for baseline renal function affect the classification
      and prognosis of acute kidney injury.
AB  - Studies of acute kidney injury usually lack data on pre-admission kidney function
      and often substitute an inpatient or imputed serum creatinine as an estimate for
      baseline renal function. In this study, we compared the potential error
      introduced by using surrogates such as (1) an estimated glomerular filtration
      rate of 75 ml/min per 1.73 m(2) (suggested by the Acute Dialysis Quality
      Initiative), (2) a minimum inpatient serum creatinine value, and (3) the first
      admission serum creatinine value, with values computed using pre-admission renal
      function. The study covered a 12-month period and included a cohort of 4863
      adults admitted to the Vanderbilt University Hospital. Use of both imputed and
      minimum baseline serum creatinine values significantly inflated the incidence of
      acute kidney injury by about half, producing low specificities of 77-80%. In
      contrast, use of the admission serum creatinine value as baseline significantly
      underestimated the incidence by about a third, yielding a low sensitivity of 39%.
      Application of any surrogate marker led to frequent misclassification of patient
      deaths after acute kidney injury and differences in both in-hospital and 60-day
      mortality rates. Our study found that commonly used surrogates for baseline serum
      creatinine result in bi-directional misclassification of the incidence and
      prognosis of acute kidney injury in a hospital setting.

PMID- 20042999
TI  - BDNF Val66Met is associated with introversion and interacts with 5-HTTLPR to
      influence neuroticism.
AB  - Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and
      neurotransmission, and has been linked to neuroticism, a major risk factor for
      psychiatric disorders. A recent genome-wide association (GWA) scan, however,
      found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but
      not with neuroticism. In this study, we examine the links between BDNF and
      personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI
      R), in a sample from SardiNIA (n=1560) and the Baltimore Longitudinal Study of
      Aging (BLSA; n=1131). Consistent with GWA results, we found that BDNF Met
      carriers were more introverted. By contrast, in both samples and in a meta
      analysis inclusive of published data (n=15251), we found no evidence for a main
      effect of BDNF Val66Met on neuroticism. Finally, on the basis of recent reports
      of an epistatic effect between BDNF and the serotonin transporter, we explored a
      Val66Met x 5-HTTLPR interaction in a larger SardiNIA sample (n=2333). We found
      that 5-HTTLPR LL carriers scored lower on neuroticism in the presence of the BDNF
      Val variant, but scored higher on neuroticism in the presence of the BDNF Met
      variant. Our findings support the association between the BDNF Met variant and
      introversion and suggest that BDNF interacts with the serotonin transporter gene
      to influence neuroticism.

PMID- 20043000
TI  - Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume
      shrinkage in alcoholics.
AB  - Chronic alcoholism leads to gray matter shrinkage and induces the formation of
      superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial
      superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide.
      An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain
      volumes of 76 treatment-seeking alcohol-dependent individuals were measured with
      a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal
      sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were
      estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a
      second haplotype tagging SNP, rs10370, were genotyped. The q-value package was
      used to correct for multiple comparisons. In the alcoholics, cerebrospinal fluid
      and intra-cranial volumes showed significant differences across the six diplotype
      categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was
      associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence
      of one or two copies of the low activity Ala16 allele was a risk factor for lower
      gray matter volume in alcoholics below the median alcohol consumption (p=0.03)
      but not in alcoholics above this level. White matter ratio was associated with
      sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with
      diplotypes. In this exploratory analysis, a putative functional missense variant
      of SOD2 appears to influence gray matter loss in alcoholics. This may be due to
      impaired clearance of reactive oxygen species formed as a result of alcohol
      exposure. The risk/protective effect was observed in alcoholics with lower levels
      of lifetime alcohol consumption. Highest levels of exposure may overwhelm the
      protective action of the SOD2 enzyme.

PMID- 20043001
TI  - Risk-taking behavior in a gambling task associated with variations in the
      tryptophan hydroxylase 2 gene: relevance to psychiatric disorders.
AB  - Decision making, choosing the best option from the possible outcomes, is impaired
      in many psychiatric conditions including affective disorders. We tested the
      hypothesis that variations in serotonergic genes (TPH2, TPH1, SLC6A4, HTR1A),
      which influence serotonin availability, affect choice behavior in a probabilistic
      gambling task. A population cohort (N=1035) completed a paper-and-pencil gambling
      task, filled out personality and symptom questionnaires and gave consent for the
      use of their DNA in a genetic association study. A subgroup of subjects (N=69)
      also completed a computer version of the task. The gambling task was designed to
      estimate an individual's tendency to take a risk when choosing between a smaller
      but more certain 'win' and a larger, less probable one. We genotyped seven
      haplotype tagging SNPs in the TPH2 gene, and previously reported functional
      polymorphisms from the other genes (rs1800532, 5HTTLPR, and rs6295). Carriers of
      the more prevalent TPH2 haplotype, which was previously associated with less
      active enzyme variant, showed reduced risk taking on both tasks compared with
      subjects not carrying the common haplotype. The effect of TPH2 haplotypes on risk
      taking was independent of current depression and anxiety symptoms, neuroticism
      and impulsiveness scores. We did not find an association between functional
      polymorphisms in the TPH1, SLC6A4, HTR1A genes and risk-taking behavior. In
      conclusion, our study demonstrates the role of the TPH2 gene and the serotonin
      system in risk taking and suggests that TPH2 gene may contribute to the
      expression of psychiatric phenotypes through altered decision making.

PMID- 20043002
TI  - Ambiguous-cue interpretation is biased under stress- and depression-like states
      in rats.
AB  - Negative cognitive bias-the tendency to interpret ambiguous situations
      pessimistically-is a central feature of stress-related disorders such as
      depression. The underlying neurobiology of this bias, however, remains unclear,
      not least because of a lack of translational tools. We established a new
      ambiguous-cue interpretation paradigm and, with respect to the etiology of
      depression, evaluated if environmental and genetic factors contribute to a
      negative bias. Rats were trained to press a lever to receive a food reward
      contingent to one tone and to press another lever in response to a different tone
      to avoid punishment by electric foot-shock. In the ambiguous-cue test, the lever
      press responses to tones with frequencies intermediate to the trained tones were
      taken as indicators for the rats' expectation of a positive or negative event. A
      negative response bias because of decreased positive and increased negative
      responding was found in congenitally helpless rats, a genetic animal model of
      depression. Moreover, treatment with a combined noradrenergic-glucocorticoid
      challenge, mimicking stress-related changes in endogenous neuromodulation, biased
      rats away from positive responding. This response shift was accompanied by
      neuronal activation in dentate gyrus and amygdala. Thus, environmental and
      genetic risk factors for depression induce a response bias, which resembles the
      pessimistic bias of patients suffering from depression. The behavioral paradigm
      described constitutes a useful tool to study the neuronal basis of decision
      making under ambiguous conditions and may promote innovative pharmaco- and
      psychotherapy for depression.

PMID- 20043003
TI  - A sensitive period of mice inhibitory system to neonatal GABA enhancement by
      vigabatrin is brain region dependent.
AB  - Neurodevelopmental disorders, such as schizophrenia and autism, have been
      associated with disturbances of the GABAergic system in the brain. We examined
      immediate and long-lasting influences of exposure to the GABA-potentiating drug
      vigabatrin (GVG) on the GABAergic system in the hippocampus and cerebral cortex,
      before and during the developmental switch in GABA function (postnatal days P1-7
      and P4-14). GVG induced a transient elevation of GABA levels. A feedback response
      to GABA enhancement was evident by a short-term decrease in glutamate
      decarboxylase (GAD) 65 and 67 levels. However, the number of GAD65/67
      immunoreactive (IR) cells was greater in 2-week-old GVG-treated mice. A long-term
      increase in GAD65 and GAD67 levels was dependent on brain region and treatment
      period. Vesicular GABA transporter was insensitive to GVG. The overall effect of
      GVG on the Cl(-) co-transporters NKCC1 and KCC2 was an enhancement of their
      synthesis, which was dependent on the treatment period and brain region studied.
      In addition, a short-term increase was followed by a long-term decrease in KCC2
      oligomerization in the cell membrane of P4-14 hippocampi and cerebral cortices.
      Analysis of the Ca(2+) binding proteins expressed in subpopulations of GABAergic
      cells, parvalbumin and calbindin, showed region-specific effects of GVG during P4
      14 on parvalbumin-IR cell density. Moreover, calbindin levels were elevated in
      GVG mice compared to controls during this period. Cumulatively, these results
      suggest a particular susceptibility of the hippocampus to GVG when exposed during
      days P4-14. In conclusion, our studies have identified modifications of key
      components in the inhibitory system during a critical developmental period. These
      findings provide novel insights into the deleterious consequences observed in
      children following prenatal and neonatal exposure to GABA-potentiating drugs.

PMID- 20043004
TI  - R7BP complexes with RGS9-2 and RGS7 in the striatum differentially control motor
      learning and locomotor responses to cocaine.
AB  - In the striatum, signaling through G protein-coupled dopamine receptors mediates
      motor and reward behavior, and underlies the effects of addictive drugs. The
      extent of receptor responses is determined by RGS9-2/Gbeta5 complexes, a
      striatally enriched regulator that limits the lifetime of activated G proteins.
      Recent studies suggest that the function of RGS9-2/Gbeta5 is controlled by the
      association with an additional subunit, R7BP, making elucidation of its
      contribution to striatal signaling essential for understanding molecular
      mechanisms of behaviors mediated by the striatum. In this study, we report that
      elimination of R7BP in mice results in motor coordination deficits and greater
      locomotor response to morphine administration, consistent with the essential role
      of R7BP in maintaining RGS9-2 expression in the striatum. However, in contrast to
      previously reported observations with RGS9-2 knockouts, mice lacking R7BP do not
      show higher sensitivity to locomotor-stimulating effects of cocaine. Using a
      striatum-specific knockdown approach, we show that the sensitivity of motor
      stimulation to cocaine is instead dependent on RGS7, whose complex formation with
      R7BP is dictated by RGS9-2 expression. These results indicate that dopamine
      signaling in the striatum is controlled by concerted interplay between two RGS
      proteins, RGS7 and RGS9-2, which are balanced by a common subunit, R7BP.

PMID- 20043005
TI  - Neurochemical alterations in methamphetamine-dependent patients treated with
      cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance
      spectroscopy study.
AB  - Cytidine-5'-diphosphate choline (CDP-choline), as an important intermediate for
      major membrane phospholipids, may exert neuroprotective effects in various
      neurodegenerative disorders. This longitudinal proton magnetic resonance
      spectroscopy ((1)H-MRS) study aimed to examine whether a 4-week CDP-choline
      treatment could alter neurometabolite levels in patients with methamphetamine
      (MA) dependence and to investigate whether changes in neurometabolite levels
      would be associated with MA use. We hypothesized that the prefrontal levels of N
      acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho),
      which are related to membrane turnover, would increase with CDP-choline treatment
      in MA-dependent patients. We further hypothesized that this increase would
      correlate with the total number of negative urine results. Thirty-one treatment
      seekers with MA dependence were randomly assigned to receive CDP-choline (n=16)
      or placebo (n=15) for 4 weeks. Prefrontal NAA and Cho levels were examined using
      (1)H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized
      estimating equation regression analyses showed that the rate of change in
      prefrontal NAA (p=0.005) and Cho (p=0.03) levels were greater with CDP-choline
      treatment than with placebo. In the CDP-choline-treated patients, changes in
      prefrontal NAA levels were positively associated with the total number of
      negative urine results (p=0.03). Changes in the prefrontal Cho levels, however,
      were not associated with the total number of negative urine results. These
      preliminary findings suggest that CDP-choline treatment may exert potential
      neuroprotective effects directly or indirectly because of reductions in drug use
      by the MA-dependent patients. Further studies with a larger sample size of MA
      dependent patients are warranted to confirm a long-term efficacy of CDP-choline
      in neuroprotection and abstinence.

PMID- 20043006
TI  - Familial risk for mood disorder and the personality risk factor, neuroticism,
      interact in their association with frontolimbic serotonin 2A receptor binding.
AB  - Life stress is a robust risk factor for later development of mood disorders,
      particularly for individuals at familial risk. Likewise, scoring high on the
      personality trait neuroticism is associated with an increased risk for mood
      disorders. Neuroticism partly reflects stress vulnerability and is positively
      correlated to frontolimbic serotonin 2A (5-HT(2A)) receptor binding. Here, we
      investigate whether neuroticism interacts with familial risk in relation to
      frontolimbic 5-HT(2A) receptor binding. Twenty-one healthy twins with a co-twin
      history of mood disorder and 16 healthy twins without a co-twin history of mood
      disorder were included. They answered self-report personality questionnaires and
      underwent [(18)F]altanserin positron emission tomography. We found a significant
      interaction between neuroticism and familial risk in predicting the frontolimbic
      5-HT(2A) receptor binding (p=0.026) in an analysis adjusting for age and body
      mass index. Within the high-risk group only, neuroticism and frontolimbic 5
      HT(2A) receptor binding was positively associated (p=0.0037). In conclusion, our
      data indicate that familial risk and neuroticism interact in their relation to
      frontolimbic 5-HT(2A) receptor binding. These findings point at a plausible
      neurobiological link between genetic and personality risk factors and
      vulnerability to developing mood disorders. It contributes to our understanding
      of why some people at high risk develop mood disorders while others do not. We
      speculate that an increased stress reactivity in individuals at high familial
      risk for mood disorders might enhance the effect of neuroticism in shaping the
      impact of potential environmental stress and thereby influence serotonergic
      neurotransmission.

PMID- 20043008
TI  - Advances in mast cell biology: new understanding of heterogeneity and function.
AB  - Mast cells are classically viewed as effector cells of IgE-mediated allergic
      diseases. However, over the last decade our understanding has been enriched about
      their roles in host defense, innate and adaptive immune responses, and in
      homeostatic responses, angiogenesis, wound healing, tissue remodeling, and
      immunoregulation. Despite impressive progress, there are large gaps in our
      understanding of their phenotypic heterogeneity, regulatory mechanisms involved,
      and functional significance. This review summarizes our knowledge of mast cells
      in innate and acquired immunity, allergic inflammation and tissue homeostasis, as
      well as some of the regulatory mechanisms that control mast cell development,
      phenotypic determination, and function, particularly in the context of mucosal
      surfaces.

PMID- 20043007
TI  - Previous stress attenuates the susceptibility to Midazolam's disruptive effect on
      fear memory reconsolidation: influence of pre-reactivation D-cycloserine
      administration.
AB  - It is well known that, under certain boundary conditions, the retrieval of a
      stable consolidated memory results into a labile one. During this unstable phase,
      memory can be vulnerable to interference by a number of pharmacological agents,
      including benzodiazepines. One of the goals of this study was to evaluate the
      vulnerability to midazolam (MDZ) after reactivation of recent and remote
      contextual fear memories in animals that experienced a stressful situation before
      learning. Animals were subjected to a restraint session and trained in a
      contextual fear paradigm the following day; consolidated memories were
      reactivated at different times after learning and different MDZ doses (1.5, 3.0
      mg/kg) were administered to rats after reactivation. Our results show that MDZ
      did not affect memory reconsolidation in older-than-one-day memories of stressed
      animals, even after the administration of a higher MDZ dose and a longer
      reactivation session (5 min). In contrast, MDZ was effective in blocking
      reconsolidation at all memory ages in unstressed animals. In addition, the
      current research investigated whether activating NMDA sites before reactivation
      promotes the destabilization of resistant memories such as those of stressed
      animals. We tested the influence of pre-reactivation D-cycloserine (DCS), a
      partial NMDA agonist, on MDZ's effect on fear memory reconsolidation in stressed
      animals. Our findings indicate that DCS before reactivation promotes retrieval
      induced lability in resistant memory traces, as MDZ-induced memory impairment in
      stressed rats became evident with pre-reactivation DCS but not after pre
      reactivation sterile isotonic saline.

PMID- 20043010
TI  - NICU medication errors: identifying a risk profile for medication errors in the
      neonatal intensive care unit.
AB  - OBJECTIVE: To identify a risk profile for harmful medication errors in the
      neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective cross
      sectional study on NICU medication error reports submitted to MEDMARX between 1
      January 1999, and 31 December 2005. The Rao-Scott modified chi(2) test was used
      for analysis. RESULT: 6749 NICU medication error reports were submitted by 163
      health-care facilities. Administering errors accounted for approximately one half
      of errors, and human factors were the most frequently cited cause of error.
      Patient age was not associated with an increased likelihood of an error being
      harmful (P=0.11). Error reports involving Institute for Safe Medication Practices
      (ISMP) High-Alert Medications, occurring in the prescribing phase of medication
      processing, or involving equipment/delivery device failures were more likely to
      be harmful (P< or =0.05). CONCLUSION: Risk factors for harmful medication error
      reports include use of ISMP High-Alert Medications, the prescribing phase of the
      medication use process, and failure of equipment/delivery devices.

PMID- 20043009
TI  - Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic
      enhancer without anti-HIV activity.
AB  - GS-9350 is a new chemical entity under development as a potent, mechanism-based
      inhibitor of human cytochrome P450 3A (CYP3A) isoforms. Its intended use is to
      increase the systemic exposure of coadministered agents that are metabolized by
      CYP3A enzymes. Unlike ritonavir, which is in current clinical use for this
      purpose, GS-9350 is devoid of anti-HIV activity. The pharmacokinetics of GS-9350
      and its efficacy in increasing systemic exposure of the probe CYP3A substrate
      midazolam were examined in a study involving single- and multiple-dose
      escalations of GS-9350 from 50 to 400 mg. Single-dose escalation from 50 to 400
      mg resulted in a 164-fold increase in GS-9350 exposure, whereas multiple-dose
      escalation in the dosage range of 50-300 mg resulted in a 47-fold increase in
      exposure. GS-9350 potently inhibited midazolam apparent clearance (95%
      reduction), similar in effect to ritonavir 100 mg. GS-9350 was generally well
      tolerated at all doses, and there was no evidence of dose-limiting toxicity.
      Establishing proof-of-concept, GS-9350 is currently under phase II development as
      a potential alternative to ritonavir for use with antiretroviral agents
      (including the HIV integrase inhibitor elvitegravir) that are often prescribed
      along with a "booster" drug.

PMID- 20043011
TI  - Effect of ampicillin on the bleeding time of neonatal intensive care unit
      patients.
AB  - OBJECTIVE: Studies in adults indicate that ampicillin, in a dose-dependent
      manner, impairs platelet function and moderately prolongs the bleeding time
      (generally by 60 to 90 s). Unlike aspirin, the inhibition induced by ampicillin
      involves both reversible and irreversible mechanisms and is not observed
      immediately after initial dosing (generally requiring approximately 24 h).
      Ampicillin is administered commonly to neonatal intensive care unit (NICU)
      patients, but its effect on bleeding time in this population has not been
      reported earlier. STUDY DESIGN: We performed neonatal template bleeding times and
      platelet function analyzer (PFA)-100 tests on 15 NICU patients before and at
      various intervals after intravenous ampicillin dosing. RESULT: Neonates were only
      studied if no beta-lactam antibiotics were administered to their mother during
      labor, and if they had ampicillin ordered by the clinician at a dose of 50 to 100
      mg kg(-1) every 12 h. Subjects ranged from 33 to 41 weeks gestation and weighed
      1760 to 3835 g. Bleeding times before the first ampicillin dose (n=15) averaged
      134 s (95% confidence interval (CI), 120 to 148 s) and PFA-100 times averaged 123
      s (95% CI, 96 to 149 s). After the first dose of ampicillin (n=5), bleeding times
      and PFA-100 times did not increase, but after the third (n=5) and fourth doses
      (n=4) bleeding times lengthened by an average of 60 s (95% CI, 37 to 83 s,
      P<0.001) and PFA-100 times lengthened by an average of 20 s (95% CI, -20 to 60 s,
      P=0.15). CONCLUSION: Ampicillin administered intravenously to NICU patients
      prolongs the bleeding time, with a magnitude-of-effect and time-to-effect similar
      to that shown earlier in adults.

PMID- 20043013
TI  - Corticotropin-releasing hormone stimulates the in situ generation of mast cells
      from precursors in the human hair follicle mesenchyme.
AB  - Hair follicles (HFs) maintain a peripheral, functional equivalent of the
      hypothalamic-pituitary-adrenal (HPA) axis, whose most proximal element is
      corticotropin-releasing hormone (CRH). The mast cell (MC)-rich connective-tissue
      sheath (CTS) of mouse vibrissa HFs harbors MC precursors. Differentiation of
      these MC precursors into mature MCs can be induced by stem cell factor (SCF). We
      have investigated whether the MC progenitors of normal human scalp HF CTS respond
      to stimulation with CRH. Microdissected anagen HFs and full-thickness scalp skin
      were treated with CRH (10(-7) M). CRH treatment induced the degranulation of CTS
      MCs, in addition to increasing the number of CTS MCs in full-thickness skin and
      HF organ cultures in situ. In the latter, cells with characteristic MC features
      emigrated from the CTS. CRH-receptor protein expression in the CTS was
      colocalized with Kit expression on some CTS MCs in situ. CRH treatment
      upregulated SCF mRNA and protein expression within the HF epithelium. In skin
      organ culture, CRH-induced degranulation of CTS MCs was abolished by anti-SCF
      antibody. We demonstrate that human skin is an extramedullary reservoir for MC
      precursors, and we have identified a regulatory loop between CRH and SCF
      signaling. This highlights a previously unpublished finding about neuroendocrine
      control of human MC biology.

PMID- 20043012
TI  - Association of prediagnostic serum vitamin D levels with the development of basal
      cell carcinoma.
AB  - We investigated the association between serum 25-hydroxyvitamin D (25(OH)D)
      levels and basal cell carcinoma (BCC) risk in a nested case-control study at
      Kaiser Permanente Northern California (KPNC). A total of 220 case patients with
      BCC diagnosed after serum collection were matched to 220 control subjects. We
      estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional
      logistic regression. Fully adjusted models included body mass index (BMI),
      smoking, education, sun-exposure variables, X-ray exposure, and personal history
      of cancer. For each measure of serum 25(OH)D (continuous, clinically relevant
      tertiles, quintiles), we found an increased risk of BCC in unadjusted models
      (OR=1.03, 95% CI 1.00-1.05, P<0.05; OR=3.98, 95% CI: 1.31-12.31, deficient vs.
      sufficient, test for trend P-value <0.01; OR=2.32, 95% CI: 1.20-4.50, 1st vs. 5th
      quintile, test for trend P-value 0.03). In fully adjusted models, the values
      attenuated slightly (OR=1.02, 95% CI 1.00-1.05, P<0.05; OR=3.61, 95% CI: 1.00
      13.10, deficient vs. sufficient, t-trend P=0.03; OR=2.09 1st vs. 5th quintile,
      95% CI: 0.95-4.58, t-trend P=0.11). Our findings suggest that higher
      prediagnostic serum 25(OH)D levels may be associated with increased risk of
      subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and
      serum 25(OH)D levels may be warranted.

PMID- 20043014
TI  - How good are clinical severity and outcome measures for psoriasis?: quantitative
      evaluation in a systematic review.
AB  - A large number of clinical measures of psoriasis are used in clinical trials and
      daily practice. These measures lack uniformity and validation. However, valid
      outcome and severity measures for psoriasis are a prerequisite for fully
      informative clinical research and evidence-based medicine. The purpose of this
      study was to identify all clinical measures of psoriasis severity and outcome in
      use and to evaluate the quality of these measures using clinimetric criteria; we
      identified 53 separate clinical measures, which were regrouped into 11 measures
      for quality analysis. No measure could be scored on all items used in the
      clinimetric analysis. The Lattice System Physician's Global Assessment and
      Physician's Global Assessment were most highly noted. We conclude that none of
      the psoriasis measures is adequately validated. The Psoriasis Area and Severity
      Index is the most commonly used clinical measure in research, but it has
      substantial limitations such as low response distribution, no consensus on
      interpretability, and low responsiveness in mild disease. Nevertheless, because
      of its widespread use the Psoriasis Area and Severity Index permits some degree
      of comparison of results among clinical trials. Overall, no best instrument was
      identified, and different situations may call for different measures.

PMID- 20043015
TI  - Relationship between germline MC1R variants and BRAF-mutant melanoma in a North
      Carolina population-based study.

PMID- 20043016
TI  - Real-time monitoring of membrane cholesterol reveals new insights into epidermal
      differentiation.
AB  - Cholesterol is organized in distinctive liquid-ordered micro-domains within
      biological membranes called lipid rafts. These micro-domains direct multiple
      physiological functions in mammalian cells by modulating signaling processes.
      Recent findings suggest a role for lipid rafts in cellular processes in human
      keratinocytes such as early differentiation and apoptosis. However, research of
      lipid rafts is hindered by technological limitations in visualizing dynamic
      cholesterol organization in plasma membranes. This study addresses a real-time,
      non-invasive method for the long-term observation of cholesterol reorganization
      in plasma membranes. In addition, this study also addresses the dynamic process
      of cholesterol depletion and repletion in primary human keratinocytes.
      Cholesterol reorganization was measured by observed changes in cellular
      impedance. Disruption of lipid rafts with low concentrations of methyl-beta
      cyclodextrin (MbetaCD) resulted in an increase in the proliferative capacity of
      keratinocytes, which was assessed using real-time proliferation curves and
      adenosine triphosphate (ATP)-based proliferation assays. Quantitative PCR showed
      a concomitant decrease in messenger RNA (mRNA) expression of the early
      differentiation markers keratins 1 and 10. Conversely, specific cholesterol
      reintegration led to a 4.5-fold increase in keratin 2 mRNA expression, a marker
      for late keratinocyte differentiation, whereas depletion resulted in a
      significant downregulation. These findings imply a strictly controlled mechanism
      for the regulation of membrane cholesterol composition in both early and terminal
      keratinocyte differentiation. The impedance-based method that this study
      addresses further enhances our understanding of how physiological processes in
      keratinocytes are controlled by membrane cholesterol.

PMID- 20043017
TI  - Progressive macular hypomelanosis is associated with a putative Propionibacterium
      species.

PMID- 20043018
TI  - 2009 in reflection.

PMID- 20043020
TI  - Deal watch : BMS acquires rights for IL-6 inhibitor.

PMID- 20043021
TI  - Trial watch: Antisense agent reduces LDL-cholesterol levels in high-risk
      patients.

PMID- 20043022
TI  - Market watch: upcoming market catalysts in Q1 of 2010.

PMID- 20043023
TI  - Patent watch: EPO rejects reach through claims.

PMID- 20043024
TI  - An audience with...Marc Cluzel.
AB  - Executive Vice President, R&D, Sanofi-Aventis, Paris, France. In November 2009,
      Marc Cluzel was appointed executive Vice President (VP) of R&D at Sanofi-Aventis.
      He has a medical and biochemical education from the university of Montpellier,
      France, and was a Visiting Assistant Professor at the Johns Hopkins University,
      Baltimore, USA, then a Research Associate at Guy's Hospital in London, UK, before
      joining Sanofi-Aventis in 1991. He was appointed VP of International Development
      in 2001, Senior VP of International Development in 2005 and Senior VP of R&D in
      January 2007.

PMID- 20043025
TI  - Respiratory syncytial virus market.

PMID- 20043026
TI  - Pazopanib.
AB  - In October 2009, pazopanib (Votrient; GlaxoSmithKline)--a multikinase inhibitor
      with targets that include vascular endothelial growth factor receptors--was
      approved by the US FDA for the treatment of advanced renal cell carcinoma.

PMID- 20043027
TI  - Subcellular targeting strategies for drug design and delivery.
AB  - Many drug targets are localized to particular subcellular compartments, yet
      current drug design strategies are focused on bioavailability and tissue
      targeting and rarely address drug delivery to specific intracellular
      compartments. Insights into how the cell traffics its constituents to these
      different cellular locations could improve drug design. In this Review, we
      explore the fundamentals of membrane trafficking and subcellular organization, as
      well as strategies used by pathogens to appropriate these mechanisms and the
      implications for drug design and delivery.

PMID- 20043028
TI  - Recognizing and avoiding siRNA off-target effects for target identification and
      therapeutic application.
AB  - Small interfering RNAs (siRNAs) are widely used to study gene function owing to
      the ease with which they silence target genes, and there is considerable interest
      in their potential for therapeutic applications. In a remarkably short time since
      their discovery, siRNAs have entered human clinical trials in various disease
      areas. However, rapid acceptance of the use of siRNAs has been accompanied by
      recognition of several hurdles for the technology, including a lack of
      specificity. Off-target activity can complicate the interpretation of phenotypic
      effects in gene-silencing experiments and can potentially lead to unwanted
      toxicities. Here, we describe the types of off-target effects of siRNAs and
      methods to mitigate them, to help enable effective application of this exciting
      technology.

PMID- 20043030
TI  - Broadening access to electronic healthcare databases.

PMID- 20043029
TI  - Key factors in the discovery and development of new antiepileptic drugs.
AB  - Since the early 1990s, many new antiepileptic drugs (AEDs) that offer appreciable
      advantages in terms of their favourable pharmacokinetics, improved tolerability
      and lower potential for drug-drug interactions have entered the market. However,
      despite the therapeutic arsenal of old and new AEDs, approximately 30% of
      patients with epilepsy still suffer from seizures. Thus, there remains a
      substantial need for the development of more efficacious AEDs for patients with
      refractory seizures. Here, we briefly review the emerging knowledge on the
      pathological basis of epilepsy and how it might best be used in the design of new
      therapeutics. We also discuss the current approach to AED discovery and highlight
      some of the unique features of newer models of pharmacoresistance and
      epileptogenesis that have emerged in recent years.

PMID- 20043031
TI  - Orphan products: an emerging trend in drug approvals.

PMID- 20043032
TI  - Is a Mass Immunization Program for Pandemic (H1N1) 2009 Good Value for Money?
      Early Evidence from the Canadian Experience.
AB  - This work contributes informed estimates to the current debate about the pandemic
      (H1N1) 2009 mass immunization program's economic merits. We performed a cost
      utility analysis of the (H1N1) 2009 mass immunization program in Ontario,
      Canada's most populous province. The analysis is based on a simulation model of a
      pandemic (H1N1) 2009 outbreak, surveillance data, and administrative data. We
      consider no immunization versus mass immunization reaching 30% of the population.
      Immunization program costs are expected to be $118 million in Ontario. Our
      analysis indicates this program will reduce influenza cases by 50%, preventing 35
      deaths, and cutting treatment costs in half. A pandemic (H1N1) 2009 immunization
      program is likely to be highly cost-effective.

PMID- 20043033
TI  - Epidemiological characteristics and low case fatality rate of pandemic (H1N1)
      2009 in Japan.
AB  - Pandemic (H1N1) 2009 has been causing large outbreaks in Japan. Yet, the case
      fatality rate (CFR) remains low and only 85 deaths have been confirmed as of
      December 17, 2009. Surveillance data was analyzed to define epidemiological
      characteristics of pandemic (H1N1) 2009 in Japan. It was shown that most of the
      reported influenza-like illness cases and hospitalizations have occurred in those
      aged 5-9 years and 10-14 years, in whom CFR is extremely low. However, CFRs are
      higher in small children (<5 years) and adults. The transmission to these age
      groups may possibly have been minimized through aggressive suspension of classes
      in schools.

PMID- 20043034
TI  - Symptomatic infections less frequent with H1N1pdm than with seasonal strains:
      Antoine Flahault, Xavier de Lamballerie, Camille Pelat, Nicolas Salez, Thomas
      Hanslik.
AB  - A serosurvey conducted in a sample of first quarter pregnant women in France at
      week 48-49 of 2009 exhibit a seroprevalence level of 10.6%. It has been
      extrapolated in male and female population living in France mainland, aged 20-39
      yr, that 1,712,000, 95%CI (1,112,700 - 2,311,300) people were recently infected
      by H1N1pdm (recently vaccinated women were excluded from analysis). From week 36
      to 46-47 of 2009, 336,288, 95%CI (207,303-421,299) patients visited their general
      practitioners with clinical influenza in France, mainland. We then extrapolated
      the proportion of symptomatic H1N1pdm influenza in both males and females aged 20
      39 yr who visited their GP to be 19.6%.

PMID- 20043035
TI  - Alpha-lipoic Acid and diabetic neuropathy.
AB  - Diabetic neuropathy presents a major public health problem. It is defined by the
      symptoms and signs of peripheral nerve dysfunction in diabetic patients, in whom
      other causes of neuropathy have been excluded. Pathogenetic mechanisms that have
      been implicated in diabetic neuropathy are: a) increased flux through the polyol
      pathway, leading to accumulation of sorbitol, a reduction in myo-inositol, and an
      associated reduced Na+-K+-ATPase activity, and b) endoneurial microvascular
      damage and hypoxia due to nitric oxide inactivation by increased oxygen free
      radical activity. Alpha-lipoic acid seems to delay or reverse peripheral diabetic
      neuropathy through its multiple antioxidant properties. Treatment with alpha
      lipoic acid increases reduced glutathione, an important endogenous antioxidant.
      In clinical trials, 600 mg alpha-lipoic acid has been shown to improve
      neuropathic deficits. This review focuses on the relationship of alpha-lipoic
      acid and auto-oxidative glycosylation. It discusses the impact of alpha-lipoic
      acid on hyperglycemia-induced oxidative stress, and examines the role of alpha
      lipoic acid in preventing glycation process and nerve hypoxia.

PMID- 20043036
TI  - Mitochondrial DNA variants in the pathogenesis of type 2 diabetes - relevance of
      asian population studies.
AB  - Mitochondrial dysfunction involves defective insulin secretion by pancreatic beta
      cells, and insulin resistance in insulin-sensitive tissues such as muscle and
      adipose tissue. Mitochondria are recognized as the most important cellular source
      of energy, and the major generator of intracellular reactive oxygen species
      (ROS). Intracellular antioxidative systems have been developed to cope with
      increased oxidative damage. In case of minor oxidative stress, the cells may
      increase the number of mitochondria to produce more energy. A mechanism called
      mitochondrial biogenesis, involving several transcription factors and regulators,
      controls the quantity of mitochondria. When oxidative damage is advanced beyond
      the repair capacity of antioxidative systems, then oxidative stress can lead to
      cell death. Therefore, this organelle is central to cell life or death. Available
      evidence increasingly shows genetic linkage between mitochondrial DNA (mtDNA)
      alterations and type 2 diabetes (T2D). Based on previous studies, the mtDNA 16189
      variant is associated with metabolic syndrome, higher fasting insulin
      concentration, insulin resistance index and lacunar cerebral infarction. These
      data support the involvement of mitochondrial genetic variation in the
      pathogenesis of T2D. Importantly, phylogeographic studies of the human mtDNAs
      have revealed that the human mtDNA tree is rooted in Africa and radiates into
      different geographic regions and can be grouped as haplogroups. The Asian
      populations carry very different mtDNA haplogroups as compared to European
      populations. Therefore, it is critically important to determine the role of mtDNA
      polymorphisms in T2D.

PMID- 20043037
TI  - Preclinical and Clinical Data on Extraglycemic Effects of GLP-1 Receptor
      Agonists.
AB  - The diverse actions of the incretin hormone glucagon-like peptide (GLP)-1 include
      insulinotropic, beta-cell preservative, cardioprotective and vasodilatory
      effects. This spectrum makes GLP-1 an appealing therapeutic option for patients
      with type 2 diabetes. However, its rapid metabolism by the enzyme dipeptidyl
      peptidase (DPP)-4 renders it impractical. Incretin-based analogues have been
      developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to
      hamper its degradation (DPP-4 inhibitors). Evidence suggests that GLP-1 receptor
      agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic
      effects. For example, GLP-1 receptor agonists deliver supraphysiologic levels of
      GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4
      inhibition conserves native GLP-1 resulting in concentrations within the
      physiologic range. Furthermore, GLP-1 receptor agonists induce glucose-dependent
      insulin secretion, beta-cell protection, and other extraglycemic benefits such as
      weight loss and improvement in markers of cardiovascular risk. In contrast, DPP-4
      inhibitors are weight neutral and have modest effects on glucose control. DPP-4
      inhibition is dependent on the availability of endogenous GLP-1, which appears to
      be adversely affected by type 2 diabetes and its progression. Therefore, DPP-4
      inhibitors may be better suited for patients with mild hyperglycemia without
      comorbidities. This review examines the present understanding of the pancreatic
      effects of endogenous GLP-1, and the extrapancreatic actions it exerts on human
      bodily systems. Also, it analyzes available preclinical and clinical data on
      incretin therapies with respect to glycemia, lipids, blood pressure, and weight.

PMID- 20043038
TI  - Mesenchymal stem cells derived from bone marrow of diabetic patients portrait
      unique markers influenced by the diabetic microenvironment.
AB  - Cellular microenvironment is known to play a critical role in the maintenance of
      human bone marrow-derived mesenchymal stem cells (BM-MSCs). It was uncertain
      whether BM-MSCs obtained from a 'diabetic milieu' (dBM-MSCs) offer the same
      regenerative potential as those obtained from healthy (non-diabetic) individuals
      (hBM-MSCs). To investigate the effect of diabetic microenvironment on human BM
      MSCs, we isolated and characterized these cells from diabetic patients (dBM
      MSCs). We found that dBM-MSCs expressed mesenchymal markers such as vimentin,
      smooth muscle actin, nestin, fibronectin, CD29, CD44, CD73, CD90, and CD105.
      These cells also exhibited multilineage differentiation potential, as evident
      from the generation of adipocytes, osteocytes, and chondrocytes when exposed to
      lineage specific differentiation media. Although the cells were similar to hBM
      MSCs, 6% (3/54) of dBM-MSCs expressed proinsulin/C-peptide. Emanating from the
      diabetic microenvironmental milieu, we analyzed whether in vitro reprogramming
      could afford the maturation of the islet-like clusters (ICAs) derived from dBM
      MSCs. Upon mimicking the diabetic hyperglycemic niche and the supplementation of
      fetal pancreatic extract, to differentiate dBM-MSCs into pancreatic lineage in
      vitro, we observed rapid differentiation and maturation of dBM-MSCs into islet
      like cell aggregates. Thus, our study demonstrated that diabetic hyperglycemic
      microenvironmental milieu plays a major role in inducing the differentiation of
      human BM-MSCs in vivo and in vitro.

PMID- 20043039
TI  - Physical activity and reported barriers to activity among type 2 diabetic
      patients in the United arab emirates.
AB  - OBJECTIVES: This study was designed to assess the physical activity practice
      among type 2 diabetic patients in the United Arab Emirates (UAE). METHODS: This
      is a cross-sectional study of type 2 diabetic patients who participated in the
      outpatient clinics in Al-Ain District, during 2006. The patients completed an
      interviewer-administered questionnaire, and measurements of blood pressure, body
      mass index, body fat, abdominal circumference, glycemic control (HbA1c), and
      fasting lipid profile. RESULTS: Of the 390 patients recruited, only 25% reported
      an increase in their physical activity levels following the diagnosis of
      diabetes, and only 3% reported physical activity levels that meet the recommended
      guidelines. More than half of the study subjects had uncontrolled hypertension
      (53%) and unacceptable lipid profiles; 71% had a high low-density lipoprotein
      (LDL), 73% had low high-density lipoprotein (HDL), and 59% had
      hypertriglyceridemia. Forty-four percent were obese and a further 34% were
      overweight. Abdominal obesity was also common (59%). Only 32% had an acceptable
      glycemic control. CONCLUSIONS: The physical activity practice of type 2 diabetic
      patients in the UAE is largely inadequate to meet the recommended level necessary
      to prevent or ameliorate diabetic complications. Interventions aiming at
      overcoming the barriers to physical activity are urgently needed.

PMID- 20043040
TI  - Imaging Pancreatic Beta-Cells: Update from the 4th Workshop of the National
      Institutes of Health, Washington DC, April 2009.
AB  - There is a crucial need for developing clinically useful approaches to measure
      pancreatic islet mass and function. Islets represent a small percentage of the
      tissue located in the abdominal cavity. They remain difficult to study in vivo by
      non-invasive techniques due to the lack of a specific probe. Also, it is
      difficult to correlate imaging signals and changes in beta-cell mass. Development
      of new and reliable cell markers are currently in progress. A major issue for the
      immediate future, is to gain a better understanding of the mechanisms leading to
      diabetes, and to increase the possibilities for studying islet function in vivo.
      Once diabetes occurs, islet transplantation is an option. However, the fate of
      the graft over time remains difficult to follow, due to the lack of tools to
      monitor rejection and inflammation before islet graft loss. The aim of this
      workshop was to gather the current knowledge on beta-cell imaging, including
      cross-linking to other field as oncology and neuroimaging.

PMID- 20043041
TI  - c-myb activates CXCL12 transcription in T47D and MCF7 breast cancer cells.
AB  - Chemokine C-X-C motif ligand 12 (CXCL12) is a potent chemotactic and angiogenic
      factor that has been proposed to play a role in organ-specific metastasis and
      angiogenic activity in several malignancies. In this study, we found that the
      overexpression of c-myb could elevate CXCL12 mRNA level and CXCL12 promoter
      activity in human T47D and MCF-7 breast cancer cells. Chromatin
      immunoprecipitation assay demonstrated that c-myb could bind to the CXCL12
      promoter in the cells transfected with cmyb expression vector. c-myb siRNA
      attenuated CXCL12 promoter activity and the binding of c-myb to the CXCL12
      promoter in T47D and MCF-7 cells. These results indicated that c-myb could
      activate CXCL12 promoter transcription.

PMID- 20043042
TI  - Evaluation of Ca2+ permeability of nicotinic acetylcholine receptors in
      hypothalamic histaminergic neurons.
AB  - Hypothalamic histaminergic tuberomammillary (TM) neurons express nicotinic
      acetylcholine receptors (nAChRs) with kinetic and pharmacological properties
      resembling those of highly Ca(2+) permeable alpha7 nAChRs. However, the Ca(2+)
      permeability of TM nAChR channels has not been determined. To directly evaluate
      the Ca(2+) permeability of TM nAChRs, patch-clamp recordings were conducted using
      non-cultured acutely dissociated TM neurons and external solutions containing low
      (2 mM) and high (20 mM) concentrations of Ca(2+). A shift in the reversal
      potentials was determined from the current-voltage relationships and the
      permeability ratio, P(Ca)/P(Na), was estimated within the Goldman-Hodgkin-Katz
      constant field approximation. TM nAChRs were found to be highly Ca(2+) permeable
      with the permeability ratio, P(Ca)/P(Na)(nAChR) being approximately 5.9 and the
      fractional Ca(2+) current, P(f)(nAChR) being approximately 10.1% at -60 mV. As a
      positive control for the applied methods and analysis, the permeability ratio,
      P(Ca)/P(Na)(NMDAR) being approximately 8.3 and the fractional Ca(2+) current,
      P(f)(NMDAR) being approximately 13.6% at -60 mV for NMDA receptors were
      determined using non-cultured acutely dissociated hippocampal pyramidal neurons
      and found similar to previously reported values. Therefore, these results
      demonstrate that native TM nAChRs are highly Ca(2+) permeable, but approximately
      1.4 fold less permeable to Ca(2+) than native hippocampal pyramidal NMDA
      receptors.

PMID- 20043043
TI  - Expression, identification and biological effects of a novel VPAC2-specific
      agonist with high stability and bioactivity.
AB  - The development of rBAY, a recombinant peptide with the similar sequence of
      synthetic BAY55-9837, as a potential peptide therapeutic for type 2 diabetes is
      still a challenge mainly because of its poor stability in aqueous solution. To
      improve the peptide stability and bioactivity and investigate its biological
      effects for VPAC2-specific activation, RBAYL with 31 aa was designed based on
      sequence alignments of pituitary adenylate cyclase-activating peptides (PACAPs),
      vasoactive intestinal peptide (VIP), and related analogs and generated through
      sitedirected mutagenesis. Stability analysis showed that the prepared RBAYL with
      three mutations (N9Q, V17L, and N28K) were much more stable than rBAY. rRBAYL
      (the recombinant RBAYL) was expressed and purified by gene-recombination
      technology via native thiol ligation on solid beads. As much as 27.7 mg rRBAYL
      peptide with purity over 98% was obtained from 1 L of LB medium without expensive
      high-performance liquid chromatography refinements. The bioactivity assay of
      rRBAYL showed that it displaced [(125)I]PACAP38 and [(125)I]VIP from VPAC2 with a
      half-maximal inhibitory concentration of 51+/-6 and 50+/-4 nM, respectively,
      which were similar to those of the chemically synthesized RBAYL (sRBAYL) and
      lower than those of Ro25-1553, an established VPAC2 agonist. rRBAYL enhances the
      cAMP accumulation in CHO cells expressing human VPAC2 with a half-maximal
      stimulatory concentration (EC50) of 0.91 nM, whereas the receptor potency of
      rRBAYL at human VPAC1 (EC50 of 719 nM) was only 1/790 of that at human VPAC2, and
      rRBAYL had no activity toward human PAC1 receptor. Western-blot assay for glucose
      transporter 4 (GLUT4) indicated that the rRBAYL could significantly induce GLUT4
      expression more efficiently than rBAY or Ro25-1553 in adipocytes. Compared with
      rBAY, rRBAYL can more efficiently promote insulin release and decrease plasma
      glucose level in ICR mice. Our results suggested that rRBAYL is a novel
      recombinant VPAC2-specific agonist with high stability and bioactivity.

PMID- 20043044
TI  - Structural and functional alterations of two multidomain oxidoreductases induced
      by guanidine hydrochloride.
AB  - The unfolding and refolding of two multidomain oxidoreductases, bovine liver
      catalase and flavoprotein bovine milk xanthine oxidase (XO), have been analyzed
      by fluorescence spectroscopy, circular dichroism, and activity measurements. Two
      intermediates, a partially folded active dimer disassembled from the native
      tetramer and a partially folded inactivated monomer, are found to exist in the
      conformational changes of catalase induced by guanidine hydrochloride (GdnHCl).
      Similarly, two intermediates, an active, compacted intermediate bound by flavin
      adenine dinucleotide (FAD) partially and an inactive flexible intermediate with
      FAD completely dissociated, exist in the conformational changes of XO induced by
      GdnHCl. The activity regains completely and an enhancement in activity compared
      with the native catalase or native XO is observed by dilution of catalase or XO
      incubated with GdnHCl at concentrations not >0.5 or 1.8 M into the refolding
      buffer, but the yield of reactivation for catalase or XO is zero when the
      concentration of GdnHCl is >1.5 or 3.0 M. The addition of FAD provides a
      remarkable protection against the inactivation of XO by GdnHCl under mild
      denaturing conditions, and the conformational change of XO is irreversible after
      FAD has been removed in the presence of a strong denaturing agent. These findings
      provide impetus for exploring the influences of cofactors such as FAD on the
      structure-function relationship of xanthine oxidoreductases.

PMID- 20043045
TI  - Analysis of serum cardiac biomarkers and treadmill exercise test
      electrocardiogram for the diagnosis of coronary heart disease in suspected
      patients.
AB  - The serum proteins creatine kinase isoenzyme MB (CKMB) and cardiac troponin T are
      classic biomarkers of cardiac ischemic damage in clinical practice, which can
      sensitively detect myocardial necrosis, while other two serum proteins, ischemia
      modified albumin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have
      been recently identified as novel biomarkers of myocardial ischemia. In this
      study, the four biomarkers were detected in sera from 44 eligible patients with
      suspected coronary heart disease (CHD) before and after treadmill exercise test
      (TET), electrocardiogram (ECG) was measured during TET (TET-ECG) and invasive
      examination of coronary angiography (CAG), which is the 'gold standard' of CHD
      diagnosis, was also performed. For CAG, 25 patients were positive and 19 were
      negative, whereas for TET-ECG the numbers were 19 and 25, respectively. Among
      these four biomarkers, the NT-proBNP level in CAG positive group was much higher
      than those in CAG negative group both before and after TET, with statistical
      significance before TET (P=0.008). Furthermore, according to receiver operating
      characteristic (ROC) curve, the serum biomarker NTproBNP showed diagnostic effect
      of CHD and its cutoff value was 67 pg/ml, thus 30 of the patients in this study
      were NT-proBNP positive and 14 were negative. And it was found that NT-proBNP
      obviously enhanced the sensitivity of examinations whether analyzed alone or in
      combination with TET-ECG. More importantly, all the patients who were negative in
      both NT-proBNP and TET-ECG tests turned out to be CAG negative, which means that
      the combination of these two non-invasive examinations might take the place of
      invasive examination of CAG for CHD diagnosis. Further studies with more patients
      are warranted to validate the findings in this paper.

PMID- 20043046
TI  - Low-frequency ultrasound increases non-viral gene transfer to the mouse lung.
AB  - The aim of the study was to assess if low-frequency ultrasound (US), in the range
      of 30-35 kHz, increases non-viral gene transfer to the mouse lung. US is greatly
      attenuated in the lung due to large energy losses at the air/tissue interfaces.
      The advantages of low-frequency US, compared with high-frequency US are: (i)
      increased cavitation (responsible for the formation of transient pores in the
      cell membrane) and (ii) reduced energy losses during lung penetration. Cationic
      lipid GL67/plasmid DNA (pDNA), polyethylenimine (PEI)/pDNA and naked pDNA were
      delivered via intranasal instillation and the animals were then exposed to US
      (sonoporation) at 0.07 or 0.1 MPa for 10 min. Under these conditions, US did not
      enhance GL67 or PEI-mediated transfection. It did, however, increase naked pDNA
      gene transfer by approximately 4 folds. Importantly, this was achieved in the
      absence of microbubbles, which are crucial for the commonly used high-frequency
      (1 MHz) sonoporation but may not be able to withstand nebulization in a
      clinically relevant setup. Lung hemorrhage was also assessed and shown to
      increase with US pressure in a dose-dependent manner. We have thus, established
      that low-frequency US can enhance lung gene transfer with naked pDNA and this
      enhancement is more effective than the previously reported 1 MHz US.

PMID- 20043047
TI  - shRNA targeting HDGF suppressed cell growth and invasion of squamous cell lung
      cancer.
AB  - Hepatoma-derived growth factor (HDGF), a nuclear protein with both mitogenic and
      angiogenic activity, has been reported to be mainly involved in tumorigenesis and
      the progression of non-small cell lung cancer. In this study, the HDGF expression
      was knocked down by specific-shRNA with lentivirus expression vector targeting
      HDGF in lung squamous cell carcinoma 520 cells. HDGF knocked down by shRNA
      suppressed the cell proliferation significantly both in vitro and in vivo as
      indicated by MTT, plate clone and transplanted tumor model assays. In addition,
      the knocked-down expression of HDGF also inhibited cell migration and invasion as
      shown in transwell and Boyden experiments. We concluded that HDGF acts as an
      oncogene participating in the pathogenesis of squamous cell lung cancer, and HDGF
      may be a key therapeutic target for non-small cell lung cancer.

PMID- 20043048
TI  - Mycobacterium tuberculosis FtsZ requires at least one arginine residue at the C
      terminal end for polymerization in vitro.
AB  - We examined whether C-terminal residues of soluble recombinant FtsZ of
      Mycobacterium tuberculosis (MtFtsZ) have any role in MtFtsZ polymerization in
      vitro. MtFtsZ-deltaC1, which lacks C-terminal extreme Arg residue (underlined in
      the C-terminal extreme stretch of 13 residues, DDDDVDVPPFMRR), but retaining the
      penultimate Arg residue (DDDDVDVPPFMR), polymerizes like full-length MtFtsZ in
      vitro. However, MtFtsZ-deltaC2 that lacks both the Arg residues at the C-terminus
      (DDDDVDVPPFM), neither polymerizes at pH 6.5 nor forms even single- or double
      stranded filaments at pH 7.7 in the presence of 10 mM CaCl(2). Neither
      replacement of the penultimate Arg residue, in the C-terminal Arg deletion mutant
      DDDDVDVPPFMR, with Lys or His or Ala or Asp (DDDDVDVPPFMK/H/A/D) enabled
      polymerization. Although MtFtsZ-deltaC2 showed secondary and tertiary structural
      changes, which might have affected polymerization, GTPase activity of MtFtsZ
      deltaC2 was comparable to that of MtFtsZ. These data suggest that MtFtsZ requires
      an Arg residue as the extreme C-terminal residue for polymerization in vitro. The
      polypeptide segment containing C-terminal 67 residues, whose coordinates were
      absent from MtFtsZ crystal structure, was modeled on tubulin and MtFtsZ dimers.
      Possibilities for the influence of the C-terminal Arg residues on the stability
      of the dimer and thereby on MtFtsZ polymerization have been discussed.

PMID- 20043049
TI  - OmpA-like protein Loa22 from Leptospira interrogans serovar Lai is cytotoxic to
      cultured rat renal cells and promotes inflammatory responses.
AB  - Leptospirosis renal disease is one of the common clinical manifestations of
      leptospirosis, including acute renal failure and tubulointerstitial nephritis.
      Outer membrane protein A-like protein Loa22 is a lipoprotein from Leptospira
      interrogans and has been suggested to be a corresponding virulence factor.
      However, the role of Loa22 in leptospiral nephropathy is not yet understood. In
      the present study, we constructed a vector and artificially expressed Loa22 in
      Escherichia coli BL21(DE)pLysS cells. After extensive purification, along with a
      GST tag protein control, Loa22 protein was used to test the cytotoxicity in
      cultured rat proximal tubule cells (NRK52E) and examine its effects on the
      induction of inflammatory responses. Using morphological examination, 2,3-bis(2
      methoxy-4- nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazoium hydrixide
      absorbance, lactate dehydrogenase assays and an analysis of apoptosis via flow
      cytometry, it was found that Loa22 protein mediates a direct cytotoxic effect on
      NRK52E cells in a dose-dependent manner. Using real-time PCR, western blotting
      and immunofluorescence, it was found that Loa22 protein upregulates the
      expression of toll-like receptor 2 (TLR2), induces nitric oxide synthase and
      promotes the production of nitric oxide (NO) and monocyte chemoattractant protein
      1 (MCP-1) by NRK52E cells. Additionally, using a TLR2 blocking antibody, it was
      found that enhanced NO and MCP-1 production by NRK52E cells after Loa22
      stimulation requires the activation of TLR2. Collectively, our data suggested
      that Loa22 is a critical virulence factor of L. interrogans and is involved in
      the leptospiral nephropathy through mediating direct cytotoxicity and enhancing
      inflammatory responses.

PMID- 20043051
TI  - Citation analysis of Acta Dermatovenerologica Alpina, Pannonica et Adriatica 1992
      2008.

PMID- 20043050
TI  - Apoptotic mechanism of MCF-7 breast cells in vivo and in vitro induced by
      photodynamic therapy with C-phycocyanin.
AB  - The aim of this study was to investigate the pro-apoptotic mechanism of C
      phycocyanin (C-PC)-mediated photodynamic therapy (PDT) in a murine tumor model
      and cultured MCF-7 cells. The mice were divided into four groups: control, He-Ne
      laser radiation, C-PC treatment, and C-PC treatment + He-Ne laser radiation. The
      effects of C-PC and/or laser on immune organs, immunocyte proliferation, tumor
      genesis, and apoptosis-related proteins expressions were investigated by
      immunohistochemistry, in situ hybridization, MTT, electron microscope, western
      blot, and immunofluorescence assay. The results showed that He-Ne laser treatment
      alone showed marginal effects. In C-PC-treated mice, the weight of immune organs,
      proliferation of immunocytes, and expression of pro-apoptotic Fas protein were
      increased, whereas the tumor weight and the expressions of anti-apoptotic
      proteins (NF-kappaB and P53) and CD44 mRNA were comparatively decreased. In
      vitro, C-PC was able to inhibit MCF-7 cell proliferation and cause
      ultrastructural changes including microvilli loss, formation of membrane blebs,
      and chromatin condensation. Moreover, C-PC treatment could activate caspase-9
      expression, induce cytochrome c release, and downregulate Bcl-2 expression. When
      combined with He-Ne laser irradiation, the effects of C-PC treatment were further
      enhanced. Facilitating the apoptosis signals transduction and finally leading to
      the apoptosis of MCF-7 cells may be the mechanism of the anti-tumor activities of
      C-PC-mediated PDT.

PMID- 20043052
TI  - Low prevalence of hepatitis B and C infections among HIV-infected individuals in
      Slovenia: a nation-wide study, 1986-2008.
AB  - BACKGROUND: With the increased lifespan of HIV-1 infected patients, mostly due to
      highly active antiretroviral therapy, hepatitis C virus (HCV) and hepatitis B
      virus (HBV) have recently emerged as important pathogens in these patients. HIV-1
      infection has an important negative impact on the natural history of HCV and HBV
      infections, which has consequently caused increased liverassociated and overall
      morbidity and mortality in HIV-1 infected patients. Thus, liver disease is
      currently the second leading cause of death in HIV-infected persons in Europe.
      OBJECTIVE: To determine the prevalence of HBV and HCV infection in HIV-infected
      individuals in Slovenia. METHODS AND RESULTS: 356 out of 409 Slovenian
      individuals, confirmed as HIV positive by the end of 2008, were tested for the
      presence of HBV and HCV infection. Evidence of prior and current HBV infection
      was found in 77 (21.6%) and 14 (3.9%) of HIV-positive patients, respectively. 38
      of 356 (10.7%) HIV-infected individuals were confirmed as anti-HCV positive, and
      26 of them (68.4%) were also HCV RNA positive. Concomitant active HBV and HCV
      infection was found in only two HIV-positive individuals. CONCLUSION: In a study
      carried out on the highest proportion per entire population of HIV-infected
      individuals from a certain country or geographical region, Slovenia was
      identified as the country with the lowest prevalence of HCV infection among HIV
      infected individuals.

PMID- 20043053
TI  - Assessment of general health and quality of life in patients with acne using a
      validated generic questionnaire.
AB  - OBJECTIVES: The study was designed to utilize the SF-36, a validated generic
      questionnaire, to assess acne patients' view of their general health and quality
      of life. METHODS: The subjects were 454 acne patients (237 males, 217 females)
      visiting an outpatient clinic at Qassim University. An Arabic translation of the
      SF-36 questionnaire, culturally adapted and validated, was used to assess eight
      life-quality dimensions. Data regarding demographics, disease grade, duration,
      and treatment were also included in the questionnaire. The internal consistency
      reliability of the multi-item scales was assessed using Cronbach's coefficient
      alpha. Descriptive statistics were conducted with independent and paired-sample t
      tests as well as one-way ANOVA for metric variables; and Xi(2) and Fisher's exact
      tests were used for categorical variables. Spearman's rank correlation was used
      for associations. All tests were two-sided, and the level of significance was set
      at phi < 0.05. RESULTS: The scores for physical functioning, role physical, role
      emotional, and vitality dimensions were below 60%. About 81.5% of respondents
      rated their health as either "fair" or "poor", and only 25% said their general
      health was better than the previous year. Females were more likely to report
      better general health than males (phi = 0.001). Education level negatively
      correlated with mental health, role emotional, social functioning, general
      health, and bodily pain. Rural patients showed better general health (phi =
      0.003). Married persons rated their general health better than single patients
      (phi = 0.002). Mild and shorter-duration acne was associated with a better
      general health score compared to the previous year (phi = 0.01 and 0.001,
      respectively). Patients that had received treatment were significantly better
      regarding role physical, vitality, and mental health dimensions, whereas topical
      treatment was significantly better in the vitality dimension than oral therapy.
      The patients treated also rated their general health better than the previous
      year (phi = 0.0001). CONCLUSIONS: The presence of acne vulgaris per se is the
      most significant factor underlying patients' low perception of their general
      health. Patients' education about the disease and social support play a
      considerable role in better disease perception and can improve patients' quality
      of life.

PMID- 20043054
TI  - Hidradenitis suppurativa: a disease with male predominance in Tunisia.
AB  - BACKGROUND: hidradenitis suppurativa (HS) is a chronic inflammatory, suppurating,
      fistulizing, and scar-producing disease of apocrine gland-bearing skin. The
      diagnosis is primarily clinical, based on the presence of both sinus tracts and
      abscesses with a characteristic distribution. OBJECTIVE: Review of
      epidemiological, clinical, and prognostic characteristics of HS and discussion of
      the etiopathogenic aspects of this chronic problem. PATIENTS AND METHODS: We
      retrospectively report all cases of HS followed at the Department of Dermatology
      between January 1985 and December 2008. RESULTS: Eleven patients (10 male and 1
      female), with a mean age of 35.2 years (range 21 dash, vertical53 years) at HS
      diagnosis were followed for HS. The average age of disease onset was 23.9 years.
      The median delay between onset of symptoms and diagnosis was 144 months (range 1
      dash, vertical408 months). Clinical features showed inflamed discharging papules
      or nodules, painful tender erythematous nodules, and double-ended comedones. The
      disease mainly affected the axillary, anal, perineal, and genital areas.
      Histologically, dermal features showed active folliculitis or abscess, sinus
      tract formation, fibrosis, and granuloma formation. Pathological associations
      (Darier's disease and Down syndrome) were noted in two patients. Treatment
      consisted of antibiotics in eight patients, retinoids (1 mg/kg/ day) in three
      patients, and surgery in three patients. The mean follow-up was 13 months (range
      2 dash, vertical30 months). Recurrence of lesions was observed in all patients
      approximately 1 month after treatment withdrawal. The Down syndrome patient
      developed vaginal hydrocele of the testis as a complication of his staphylococcic
      ulcers. In all cases healing occurred with substantial scarring. DISCUSSION: An
      obvious male predominance was noted in our patients as well as a delay in the
      diagnosis of HS, which could be explained by non-recognition of the disease by
      non-specialists that see the patients at the primary-care level.

PMID- 20043055
TI  - A large hymenal polyp in a 21-year-old virgin.
AB  - Pathological conditions of the hymen are rare in everyday medical practice. They
      are usually encountered in the pediatric patient population and are sometimes a
      matter of forensic interest. We report an interesting case of a large hymenal
      polyp in an adolescent virgin that presented only a cosmetic problem. The polyp
      was excised, the hymenal ring was preserved, and the sample was histologically
      verified.

PMID- 20043056
TI  - Oral submucous fibrosis in a young patient.
AB  - A seventeen-year-old male presented with a restriction in the oral cavity. The
      oral mucosa was white and he could not protrude his tongue. For 4 years he had
      habitually held a powdery material containing betel nut in the oral vestibule for
      several minutes a day. A biopsy of the labial mucosa was carried out and a
      diagnosis of oral submucous fibrosis was confirmed. This is a premalignant
      condition. Oral submucous fibrosis is very rare in young patients.

PMID- 20043057
TI  - Zosteriform lymphangioma circumscriptum.
AB  - Lymphangioma circumscriptum (LC) is a form of lymphangioma involving skin and
      subcutaneous tissue. It is evident as translucent vesicles of varying size,
      though commonly 2 to 4 mm, and of a pink, red, or black hue. It is localized to
      the dermis, frequently extending deeply and laterally. LC may resemble other
      entities, such as metastatic carcinoma of the skin, lymphangiectasis, or herpes
      zoster. We report an unusual verruciform, zosteriform form of LC.

PMID- 20043058
TI  - Skin manifestations in familial heterozygous hypercholesterolemia.
AB  - Familial hypercholesterolemia, a form of primary hyperlipoproteinemia, is an
      autosomal dominant disorder characterized by an increase in serum LDL cholesterol
      concentrations. Multiple types of xanthomas occur, such as tendinous, tuberous,
      subperiosteal, and xanthelasma. Intertriginous xanthomas are rare, but if present
      are pathognomonic in this disorder. We report a patient with multiple xanthomas
      including the very rare intertriginous variety.

PMID- 20043059
TI  - Cutaneous horn: a potentially malignant entity.
AB  - A cutaneous horn is a conical, dense, hyperkeratotic protrusion that often
      appears similar to the horn of an animal. It is a morphologic designation
      referring to an unusually cohesive keratinized material, not a true pathologic
      diagnosis. Cutaneous horns occur in association with, or as a response to, a wide
      variety of underlying benign, pre-malignant, and malignant cutaneous diseases.
      The most important common concern is distinguishing a hyperkeratotic actinic
      keratosis from a cutaneous squamous cell carcinoma. Keratoacanthoma is another
      cause, as illustrated herein as a projective cutaneous tumor with a fingernail
      like appearance. The treatment of choice for cutaneous horns is shave excision
      with subsequent histopathologic evaluation to rule out underlying malignancy and
      to guide potential further therapy.

PMID- 20043060
TI  - Bacillus Calmette-Guerin vaccine- induced lupus vulgaris in a child.
AB  - Lupus vulgaris (LV) is a rare form of cutaneous mycobacterial infection in
      children. Most cases follow hematogenous or lymphatic seeding, and more rarely
      from exposure to bacillus Calmette- Guerin (BCG) vaccine. We report a child that
      received BCG vaccination and developed LV 2 months later.

PMID- 20043061
TI  - Further clarification of scientific misconduct in Acta Dermatovenerologica
      Alpina, Pannonica et Adriatica.

PMID- 20043062
TI  - High-resolution magic angle spinning magnetic resonance spectroscopy detects
      glycine as a biomarker in brain tumors.
AB  - The non-essential amino acid neurotransmitter glycine (Gly) may serve as a
      biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12
      glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3
      pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3
      adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients
      undergoing surgery for epilepsy, we tested the hypothesis that the presence of
      glycine may distinguish among these brain tumor types. Using high-resolution
      magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we
      determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly
      signals from overlapping myo-inositol (Myo) signals and tested our methodology in
      phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly
      in tumor biopsies (all combined) relative to controls; Gly levels were
      significantly elevated in LG, MT and GBM biopsies (P<or=0.05). Residual Myo
      levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control
      levels). We observed higher levels of Gly in GBM as compared to LG tumors
      (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ
      significantly from each other, the Gly:Myo ratio did distinguish GBM from MT
      (P<0.003) and from all other groups, a distinction that has not been adequately
      made previously. We conclude from these findings that Gly can serve as a
      biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for
      brain tumor classification.

PMID- 20043063
TI  - New aspects on chromosomal instability: chromosomal break-points in Fanconi
      anemia patients co-localize on the molecular level with fragile sites.
AB  - Within cytogenetic preparations chromosomal breaks can be observed in patients
      suffering from Fanconi anemia (FA), a recessively inherited syndrome with an
      extremely elevated cancer risk, but also in healthy individuals as so-called
      fragile sites (FS). It is known that FS cytogenetically co-localize with tumor-
      and evolutionary-conserved chromosomal break-points. The also suggested co
      localization of FS and FA associated break-points (FA-bp) was studied here for
      the first time systematically by molecular cytogenetics. Metaphase chromosomes
      were obtained from lymphocytes of two FA patients (FANC-A and FANC-C,
      respectively). Overall 50.58% of the investigated FA-bp correspond to cytogenetic
      regions with known FS. A detailed molecular cytogenetic study applying FS
      spanning probes revealed that 24/29 (82.8%) of analyzed FS are in concordance
      with FA-bp. Notably, FA-bp show a distribution pattern deviating from that of
      Aphidicolin induced FS. FA-bp appear more frequently within GTG-light bands and
      additionally, a yet unreported correlation was observed between break rate and
      chromosomal banding level. In future, FA-bp might serve as model for the mapping
      and analysis of otherwise rarely observable FS.

PMID- 20043064
TI  - Talaporfin-mediated photodynamic therapy for peritoneal metastasis of gastric
      cancer in an in vivo mouse model: drug distribution and efficacy studies.
AB  - Photodynamic therapy (PDT) is a potential treatment for the peritoneal
      dissemination of gastric cancer, because its cytotoxicity is limited to
      superficial lesions. We examined the accumulation of talaporfin in peritoneal
      metastatic nodules and determined the optimal laser condition for these nodules.
      We also evaluated the pathological response after therapy. We created a
      peritoneal metastasis model in nude mice using the MKN-45 EGFP cell line. We
      evaluated the accumulation of talaporfin in peritoneal metastatic nodules and
      normal organs by spectrophotometric analysis 2-8 h after i.p. talaporfin. To
      determine optimal PDT conditions, we treated metastatic nodules and the small
      intestine using multiple laser doses (2, 5, and 10 J/cm2, respectively).
      Accumulation of talaporfin was detected in metastatic nodules in higher
      intensities than in the small intestine. The fluorescent intensity of the
      peritoneal metastatic nodules gradually decreased dependent on the time interval
      between the laser treatment and talaporfin administration. Fluorescent intensity
      in the small intestine decreased more than in the metastatic nodules. The
      pathological response rates by dose were 52.5% at 2 J/cm2, 43.2% at 5 J/cm2, and
      64.4% at 10 J/cm2, respectively, when the laser treatment was used 2 h after
      talaporfin administration, whereas at 4 h, they were 20.8, 25.5, and 26.2%,
      respectively. Finally, the recommended treatment conditions were considered to be
      a 2 J/cm2 laser dose and a 4-h interval in terms of toxicity. Talaporfin-mediated
      PDT may be an effective treatment modality for patients with advanced gastric
      adenocarcinoma and metastatic peritoneal nodules.

PMID- 20043065
TI  - Forkhead box A1 transcriptional pathway in KRT7-expressing esophageal squamous
      cell carcinomas with extensive lymph node metastasis.
AB  - Prognosis of cancers with lymph node metastasis is known to be very poor;
      however, it is still controversial whether metastatic potential can be evaluated
      by expression profiles of primary tumors. Therefore, to address this issue, we
      compared gene expression profiles of 24 esophageal squamous cell carcinomas
      (ESCCs) with extensive lymph node metastasis and 11 ESCCs with no metastatic
      lymph node. However, there was no gene cluster distinguishing these two groups,
      suggesting that lymph node metastasis-associated genes are varied depending on
      cases or subgroups. Therefore, we applied a recently developed filtering method
      (S2N') to identify such genes, and successfully extracted 209 genes associated
      with node status. Among them, over-expression of CALB1, KRT7/CK7, MUC1 and
      CEA/CEACAM5 in poor prognostic cases with metastatic lymph nodes was confirmed in
      two sets of ESCCs by RT-PCR. Each often seemed to have glandular cell type
      characteristics in both the gene expression and morphology. It was also revealed
      that FOXA1 siRNA treatment of esophageal cancer cells reduced the mRNA level of
      both KRT7 and a stabilizer of epithelial-mesenchymal transition (EMT) regulator
      LOXL2, and that both FOXA1 and LOXL2 siRNAs reduced invasion and migration of
      ESCC cells. In 15 KRT7-expressing ESCCs with metastatic lymph nodes, 60%
      expressed FOXA1 and 33% expressed both FOXA1 and LOXL2. These results suggest
      that FOXA1 induces not only KRT7 but also LOXL2 in a subset of poor prognostic
      ESCCs with metastatic lymph nodes, and it is also plausible, that other FOXA1
      downstream genes could be therapeutic targets of poor prognostic ESCCs.

PMID- 20043066
TI  - Expression of fibroblast growth factor receptor 2 IIIc in human uterine cervical
      intraepithelial neoplasia and cervical cancer.
AB  - Fibroblast growth factor receptors (FGFRs) 1-3 have IIIb and IIIc isoforms, and
      we reported that FGFR2 IIIb is highly expressed in cervical keratinizing squamous
      cell carcinoma (SCC). In this study, we determined the expression and roles of
      FGFR2 IIIc in cervical intraepithelial neoplasia (CIN) and cervical cancer. In
      CINs 1 and 2, FGFR2 IIIc was found to be localized at the basal to lower two
      thirds of the squamous epithelium, whereas it was localized in most of the
      squamous epithelium, except for the superficial layer in CIN 3. In situ
      hybridization (ISH) analysis showed that the expression patterns of FGFR2 IIIc
      mRNA are similar to those of FGFR2 IIIc protein in CINs. The FGFR2 IIIc protein
      was detected in all invasive cervical cancer patients (29 cases) and its mRNA was
      found to be strongly expressed in the invasive front of cancer cell nests. FGFR2
      IIIc cDNA was stably transfected into CaSki cells, which are derived from a
      cervical SCC. The growth rates of the CaSki cells were higher than those of Mock
      cells in vitro, and the CaSki cells tended to form larger subcutaneous tumors in
      nude mice. These findings suggest that FGFR2 IIIc plays important roles in
      carcinogenesis and growth of cervical cancer cells. Anti-FGFR2 IIIc therapies may
      represent therapeutic strategies for inhibiting the growth of CIN and cervical
      cancer.

PMID- 20043067
TI  - Tranilast strongly sensitizes pancreatic cancer cells to gemcitabine via
      decreasing protein expression of ribonucleotide reductase 1.
AB  - Gemcitabine (Gem) is a dFdC analogue with activity against several solid tumors.
      Gem is intracellularly phosphorylated by dCK, leading to the production of the
      metabolite dFdCDP. dFdCDP exhibits the cytotoxic effect by inactivating
      ribonucleotide reductase larger subunit 1 (RRM1), which is a rate limiting enzyme
      for de novo DNA synthesis. To date, RRM1 expression is believed to determine
      sensitivity to Gem in pancreatic and non-small cell lung cancer. In the present
      study, we found that an anti-allergic drug, tranilast strongly enhanced the
      sensitivity of pancreatic cancer cell line KP4 to Gem. In growth inhibition
      assay, 100 microM of tranilast plus 1 microM of Gem more strongly suppressed the
      growth of KP4 at 12.7-fold in IC50 than single Gem treatment, while this compound
      no longer affected the sensitivity to other drugs such as 5-fluorouracil,
      irinotecan or paclitaxel. FACS and TUNEL analysis demonstrated the increased
      apoptotic population in KP4 cells under tranilast plus Gem, compared with single
      Gem treatment. In Western blot analysis, tranilast treatment decreased RRM1
      expression at protein level with dose-dependency in KP4 cells. Proteasome
      inhibitor MG132 disturbed the reduction of RRM1 expression in tranilast treated
      KP4 cells, indicating protein degradation by the activated proteasome.
      Transfection using siRNA against RRM1 increased the sensitivity of KP4 to Gem,
      suggesting that RRM1 suppression is an important step in increasing Gem efficacy.
      Finally, we demonstrated that tranilast reduced RRM1 protein and increased Gem
      efficacy in 4 other pancreatic cell lines. In a future, a novel chemotherapeutic
      strategy by Gem along with tranilast might improve Gem efficacy against
      pancreatic cancer.

PMID- 20043068
TI  - Expression of dipeptidyl peptidase-IV activity and/or structure homologs in human
      meningiomas.
AB  - Meningiomas are tumors derived from arachnoid cap cells that represent
      approximately 30% of all intracranial tumors. In this study, we investigated 22
      human meningiomas for the expression of dipeptidyl peptidase (DPP)-IV activity
      and/or structure homologs (DASH), including canonical DPP-IV/CD26, fibroblast
      activation protein-alpha (FAPalpha), DPP8 and DPP9. DPP-IV-like enzymatic
      activity, including all enzymatically-active DASH molecules, was found in all 18
      benign meningiomas WHO grade I and IV atypical meningiomas WHO grade II by
      continuous rate fluorimetric assay in tissue homogenates and catalytic enzyme
      histochemistry in situ. In atypical meningiomas, this activity was significantly
      higher and was associated with higher cell proliferation as detected by Ki67
      antigen immunohistochemistry. The expression of DPP-IV/CD26 and FAPalpha
      demonstrated by real-time RT-PCR and immunohistochemistry was low. As shown
      histochemically, it occurred most often on the surface of fibrous bundles and
      whorls rich in extracellular matrix. Compared to DPP-IV/CD26 and FAPalpha, the
      expression of DPP8 and DPP9 was higher and, in addition, it was present also in
      the cells inside these structures. Expression of CXCR4, the receptor of pro
      proliferative chemokine stromal cell-derived factor-1alpha (SDF-1alpha), DPP-IV
      substrate, was found in all tumors, suggesting higher values in atypical grade II
      samples. This is the first report on the expression status of dipeptidyl
      peptidase-IV and related molecules in meningiomas. It shows that DPP8 and DPP9
      prevail over canonical DPP-IV/CD26 and FAPalpha in all examined patients. In
      addition, the study suggests an increase of DPP-IV-like enzymatic activity in
      these tumors of WHO grade II.

PMID- 20043069
TI  - Silencing the Peroxiredoxin III gene inhibits cell proliferation in breast
      cancer.
AB  - Peroxiredoxin III (Prx III), an antioxidant protein found in mitochondria, plays
      an essential role in mitochondrial homeostasis. Aberrant expression of Prx III
      has been implicated in the tumorigenesis of various cancers. In this study, we
      evaluated the expression of Prx III in breast cancer tissues and elucidated its
      role in cell proliferation, a hallmark of cancer. Breast tissue microarrays
      comprising 106 breast cancer sections were stained with Prx III antibody using
      immunohistochemisty and correlated with proliferating cell nuclear antigen (PCNA)
      immunostaining. To validate the role of Prx III in cell proliferation, expression
      of Prx III was analyzed at the mRNA and protein levels by real-time RT-PCR,
      Western blotting and immunofluorescence in vitro. siRNA mediated silencing of Prx
      III in MDA-MB-231 breast cancer cells was performed and the effect on the cell
      cycle was examined. Prx III expression in patient tissue microarray samples was
      found to be positively associated with PCNA immunostaining, a proliferative
      marker. Prx III was expressed in both MCF-7 and MDA-MB-231 breast cancer cell
      lines and transient transfection with siPrx III in MDA-MB-231 cells induced
      inhibition of cell proliferation and cell cycle arrest. The data suggests that
      Prx III has a significant role in cell cycle regulation and could be a potential
      proliferation marker in breast cancer.

PMID- 20043070
TI  - Immunotherapy of breast cancer by single delivery with rAAV2-mediated interleukin
      15 expression.
AB  - Recombinant adenovirus-associated vector serotype 2 (rAAV2) is one of the most
      promising gene transfer vectors due to its advantage of causing non-pathogenic
      infection, low immunogenicity, and long-term gene expression in human clinical
      trials. Human interleukin 15 (hIL15) has been implicated in modulation of
      antitumor activity of lymphokine-activated killer (LAK) cells, including T cells
      and NK cells. In this study, the rAAV2-hIL15 vector was produced and subjected
      for treatment with xenograft JC breast cancer model. Results showed that tumor
      onset was significantly delayed, the tumor growth was suppressed, and the
      lifespan of tumor-bearing mice were prolonged by rAAV2-hIL15. In addition, rAAV2
      hIL15 was able to produce a substantial expression of IL15 protein that
      ultimately activated the cytotoxic activity of LAK cells. Furthermore, prominent
      apoptosis was observed in tumor lesions following injection of rAAV2-hIL15. Taken
      together, our results suggested that rAAV2-hIL15 appears as a new potential
      therapeutic tool for breast cancer immunotherapy.

PMID- 20043071
TI  - Combined external and intracavitary irradiation in treatment of advanced cervical
      carcinomas: predictive factors for local tumor control and early recurrences.
AB  - In a series of 131 primary cervical carcinomas in FIGO stages I-IV suitable for
      combined external pelvic and intraluminal cervical-vaginal brachytherapy
      predictive and prognostic factors were analyzed with regard to locoregional tumor
      control, recurrences and survival data. Patients with prior surgery or patients
      treated with external beam therapy alone were excluded from this series.
      Concomitant chemotherapy was given to 47 patients (36%). The external beam
      therapy was given with a four-field technique (50-60 Gy) and brachytherapy with
      high dose-rate (Ir-192) using a ring applicator set. The dose (18-30 Gy) was
      specified according to the rules in ICRU 38 (a minimum dose to the surface of the
      target volume). Three or five fractions were given once a week in parallel with
      external beam irradiation. A CT-based 3-D dose-planning system (TMS) was used for
      the external beam therapy and for the brachytherapy planning (PLATO). The mean
      age of the patients was 65 years. One hundred and seven tumors were squamous cell
      carcinomas (82%) and 24 adenocarcinomas or adenosquamous carcinomas. One hundred
      and eight tumors were in FIGO stages I-II and 23 tumors in stages III-IV. The
      mean tumor diameter was 44 mm. Most tumors (92%) were moderately well or poorly
      differentiated. The primary cure rate of the complete series was 92% and 98%
      after chemoradiotherapy. Squamous cell carcinomas had complete remission in 96%
      and adenocarcinomas in 81% (Pearson Chi-square; P=0.00002). Tumor size was also
      highly significantly associated with local tumor control. The brachytherapy dose,
      the combined external and brachytherapy dose and the number of days of
      interruption (delay) of external irradiation were all significant predictive
      factors of local tumor control. In the complete series 39 recurrences (30%) were
      recorded. A lower FIGO stage, chemoradiotherapy, squamous cell histology, diploid
      DNA-profile, a higher brachytherapy dose, more brachytherapy fractions and a
      higher total combined irradiation dose were favorable factors with regard to the
      risk of tumor recurrences. The overall survival rate was 50% and the cancer
      specific survival rate 65%. Tumor size was the strongest individual prognostic
      factor in multivariate analysis. Chemoradiotherapy therapy versus radiotherapy
      alone and squamous cell carcinomas versus adenocarcinomas were associated with
      improved survival rates. Early radiation reactions were recorded in 58% (mostly
      grade 1) and serious late radiation reactions (grade 3-4) in 11%.

PMID- 20043072
TI  - Rho GDP dissociation inhibitor alpha expression correlates with the outcome of
      CMF treatment in invasive ductal breast cancer.
AB  - Rho-GDIalpha is an inhibitor of Rho-GTPases, which is involved in cancer
      progression. Little is known about its role in breast cancer progression. There
      is evidence, that Rho-GDIalpha may modulate drug resistance of breast cancer
      cells. To assess the importance of Rho-GDIalpha as a risk factor in invasive
      ductal breast cancer, cancer specimens of three groups of patients were analyzed
      for Rho-GDIalpha RNA (group 1, N=72 and group 2, N=73) or protein expression
      (group 3, N=90). In group 1, patients did not receive any adjuvant treatment,
      whereas, in groups 2 and 3, patients were treated with anti-estrogens and/or with
      chemotherapeutical drugs. Rho-GDIalpha RNA levels, measured by RT-PCR from fresh
      frozen material, did not correlate with relapse-free survival in Kaplan-Meier
      analysis, except in a subgroup of CMF-only treated patients. In this subgroup,
      higher Rho-GDIalpha RNA levels were significantly associated with more favorable
      prognosis. Immunohistochemical analysis (group 3) confirmed the link between
      higher Rho-GDIalpha expression and better outcome. This was again particularly
      true for the CMF-only treated patients. Cox regression analysis revealed that
      high Rho-GDIalpha protein expression reduced the risk for a relapse by
      approximately 3-fold, even if adjusted for grading, tumor size, nodal and
      estrogen receptor (ER) status. The data suggest that Rho-GDIalpha is beneficial
      to patients who received adjuvant chemotherapy. Rho-GDIalpha is possibly a useful
      biomarker to predict the response of breast cancer patients to CMF treatment.

PMID- 20043073
TI  - Implication of PI3K-dependent HSP27 and p53 expression in mild heat shock
      triggered switch of metabolic stress-induced necrosis to apoptosis in A549 cells.
AB  - Previously, we showed that mild heat shock modulates patterns of cell death in
      response to glucose deprivation (GD), a common characteristic of the tumor
      microenvironment, by switching necrosis to apoptosis through ERK-dependent
      suppression of reactive oxygen species production in A549 cells. In the present
      study, we further examined the molecular mechanism underlying mild heat shock
      induced necrosis-to-apoptosis switch. We examined the possible implication of p53
      and heat shock proteins (HSPs) in the mechanism. Inhibition of p53 by pifithrin
      alpha or p53 siRNA markedly suppressed apoptosis induced by heat shock/GD. On the
      other hand, silencing of HSP27, but not of HSP70, reversed heat shock/GD-induced
      apoptosis to necrosis, and HSP27 overexpression suppressed GD-induced necrosis.
      We further demonstrate that mild heat shock activated AKT and ERK1/2 through
      phosphorylation. Prevention of PI3K by LY294002 blocked heat shock/GD-induced
      apoptosis without reversing the cell death mode to necrosis, while inhibition of
      MEK1/2 by U0126 reversed heat shock/GD-induced apoptosis to necrosis, indicating
      a different role(s) of PI3K and ERK1/2 in heat shock/GD-induced cell death mode
      determination. We also found that mild heat shock increased HSP27 and p53 protein
      levels dependent on PI3K and suppressed the GD-induced increase in RIPA-insoluble
      HSP27 and p53 protein levels dependent on PI3K and ERK1/2. In conclusion, these
      results indicate that PI3K-dependent HSP27 and p53 induction and PI3K- and ERK1/2
      dependent inhibition of the GD-induced increase in RIPA-insoluble HSP27 and p53
      protein levels by heat play a key role(s) in heat shock-mediated switch of GD
      induced necrosis to apoptosis.

PMID- 20043074
TI  - Cytotoxic effects of ultra-diluted remedies on breast cancer cells.
AB  - The use of ultra-diluted natural products in the management of disease and
      treatment of cancer has generated a lot of interest and controversy. We conducted
      an in vitro study to determine if products prescribed by a clinic in India have
      any effect on breast cancer cell lines. We studied four ultra-diluted remedies
      (Carcinosin, Phytolacca, Conium and Thuja) against two human breast
      adenocarcinoma cell lines (MCF-7 and MDA-MB-231) and a cell line derived from
      immortalized normal human mammary epithelial cells (HMLE). The remedies exerted
      preferential cytotoxic effects against the two breast cancer cell lines, causing
      cell cycle delay/arrest and apoptosis. These effects were accompanied by altered
      expression of the cell cycle regulatory proteins, including downregulation of
      phosphorylated Rb and upregulation of the CDK inhibitor p27, which were likely
      responsible for the cell cycle delay/arrest as well as induction of the apoptotic
      cascade that manifested in the activation of caspase 7 and cleavage of PARP in
      the treated cells. The findings demonstrate biological activity of these natural
      products when presented at ultra-diluted doses. Further in-depth studies with
      additional cell lines and animal models are warranted to explore the clinical
      applicability of these agents.

PMID- 20043075
TI  - An 8-gene signature, including methylated and down-regulated glutathione
      peroxidase 3, of gastric cancer.
AB  - We have identified an 8-gene signature with significant expression differences
      between gastric cancer and normal gastric tissues. This 8-gene set can predict
      the normal and cancer status of gastric tissues with more than 96% accuracy in a
      totally independent microarray dataset. The 8 genes are composed of down
      regulated KLF4, GPX3, SST and LIPF, together with up-regulated SERPINH1, THY1 and
      INHBA in gastric cancer. To corroborate the differential gene expression pattern,
      we chose GPX3 and examined its expression pattern in detail. A comparison of GPX3
      expression pattern shows a broader down-regulated pattern in multiple types of
      cancers, including cervical, thyroid, head and neck, lung cancers and melanoma
      than in healthy controls. An immuno-histostaining analysis in tissue microarrays
      confirms GPX3 down-regulation in gastric cancer. Mechanism-wise GPX3 down
      regulation in gastric cancer is due to promoter hypermethylation. Collectively,
      these results show a correct identification of 8 genes as gastric cancer
      biomarkers.

PMID- 20043076
TI  - Integrative genomic analyses of CXCR4: transcriptional regulation of CXCR4 based
      on TGFbeta, Nodal, Activin signaling and POU5F1, FOXA2, FOXC2, FOXH1, SOX17, and
      GFI1 transcription factors.
AB  - CXCR4, CD133, CD44 and ABCG2 are representative transmembrane proteins expressed
      on the surfaces of normal and/or cancer stem cells. CXCR4 is co-expressed with
      POU5F1 in endodermal precursors and adult-tissue stem cells. CXCR4 is expressed
      in a variety of human tumors, such as breast cancer, prostate cancer, pancreatic
      cancer, and gastric cancer. CXCR4 is a G protein-coupled receptor (GPCR) for
      CXCL12 (SDF1) chemokine, and the CXCL12-CXCR4 signaling axis is involved in
      proliferation, survival, migration, and homing of cancer cells. Integrative
      genomic analyses of CXCR4 gene were carried out to elucidate the mechanisms of
      CXCR4 expression in stem cells, because CXCR4 is a key molecule occupying the
      crossroads of oncology, immunology, gerontology and regenerative medicine. Human
      CXCR4 promoter region with binding sites for HIF1alpha, ETS1, NF-kappaB and GLI
      was not conserved in mouse and rat Cxcr4 orthologs. Proximal enhancer region with
      palindromic Smad-binding sites, FOX-binding site, POU-binding site, triple SOX17
      binding sites, bHLH-binding site, TCF/LEF-binding site, and double GFI1-binding
      sites was almost completely conserved among human, chimpanzee, mouse, and rat
      CXCR4 orthologs. TGFbeta, Nodal, and Activin signals induce CXCR4 upregulation
      based on Smad2/3 and FOX family members, such as FOXA2, FOXC2, and FOXH1. CXCR4
      is expressed in endodermal precursors due to the existence of triple SOX17
      binding sites around the POU-binding site instead of the POU5F1-SOX2 joint motif.
      Because CXCR4 is downregulated by p53-GFI1 signaling axis, p53 mutation in cancer
      stem cells leads to CXCR4 upregulation. CXCR4 is also upregulated by TGFbeta and
      Hedgehog signals in tumor cells at the invasion front. Small molecule compound or
      human antibody targeted to CXCR4 will be applied for cancer therapeutics focusing
      on cancer stem cells at the primary lesion as well as metastasis or recurrence
      niches, such as bone marrow and peritoneal cavity.

PMID- 20043077
TI  - Punicic acid is an omega-5 fatty acid capable of inhibiting breast cancer
      proliferation.
AB  - Pomegranate extracts have been used as anticancer agents and they contain a large
      number of potentially bioactive substances. Punicic acid is an omega-5 long chain
      polyunsaturated fatty acid found in Punica granatum (pomegranate) seed oil. A
      number of long chain fatty acids have been reported to have cancer preventive
      actions. Here we investigated the potential ability of punicic acid to affect
      growth of both an estrogen insensitive breast cancer cell line (MDA-MB-231) and
      an estrogen sensitive cell line developed from the MDA-MB-231 cells (MDA
      ERalpha7). Proliferation was inhibited 92 and 96% for MDA-MB-231 and MDA-ERalpha7
      cells, respectively compared to untreated cells by 40 microM punicic acid.
      Furthermore, punicic acid induced apoptosis in the MDA-MB-231 and MDA-ERalpha7
      cells by 86 and 91%, respectively compared to untreated control cells and
      disrupted cellular mitochondrial membrane potential. We also investigated whether
      lipid oxidation was required for the function of punicic acid by adding 20 microM
      of the antioxidant tocotrienol to the assays. This resulted in reversal of the
      effects of punicic acid on proliferation inhibition, apoptosis and disruption of
      the mitochondrial membrane potential. Finally, we evaluated the role of PKC
      signaling in the anti-cancer effects of punicic acid by performing proliferation
      assays in the presence of the PKC inhibitor bisindolymaleimide I. Proliferation
      inhibition by punicic acid was partially blocked in both the MDA-MB-231 and MDA
      ERalpha7 cells. These results suggest that punicic acid has breast cancer
      inhibitor properties that are dependent on lipid peroxidation and the PKC
      pathway.

PMID- 20043078
TI  - A kelch family protein Nd1-L functions as a metastasis suppressor in cancer cells
      via Rho family proteins mediated mechanism.
AB  - The BTB-kelch protein Nd1-L acts as an actin cytoskeleton stabilizer expressed
      ubiquitously in mouse tissues. We examined the effect of Nd1-L on cancer cell
      invasion and metastasis. Over-expression of Nd1-L in murine colon carcinoma cell
      line Colon 26 and murine melanoma cell line B16 resulted in suppression of
      pulmonary and liver metastasis after inoculation of these cells to syngeneric
      mice and in increased survival in an animal model. On the other hand, knock down
      of Nd1-L by RNA interference promoted metastasis ability of these cells.
      Increased expression of Nd1-L inhibited migration and Matrigel invasion capacity
      of cancer cell lines in vitro. Thus, Nd1-L expression inversely correlated with
      invasive and metastasis capacity of cancer cells. Furthermore, increased
      expression of Nd1-L in NIH3T3 cells inhibited growth factor induced activation of
      Rho family small GTPases such as Rho, Rac and cdc42. These results suggest that
      Nd1-L is involved in invasion and metastasis of cancer cells by regulating the
      actin cytoskeleton and Rho family proteins.

PMID- 20043079
TI  - Xanthohumol, a prenylated chalcone derived from hops, inhibits proliferation,
      migration and interleukin-8 expression of hepatocellular carcinoma cells.
AB  - Xanthohumol, the major prenylated chalcone found in hops, is well known to exert
      anti-cancer effects, but information regarding the impact on hepatocellular
      carcinoma (HCC) cells and potential adverse effects on non-tumorous hepatocytes
      is limited. Here, we show that xanthohumol at a concentration of 25 microM
      induced apoptosis in two HCC cell lines (HepG2 and Huh7). Furthermore,
      xanthohumol repressed proliferation and migration, as well as TNF induced NF
      kappaB activity and interleukin-8 expression in both cell lines at even lower
      concentrations. In contrast, xanthohumol concentrations up to 100 microM did not
      affect viability of primary human hepatocytes in vitro. In summary, our data
      showed that xanthohumol can ameliorate different pro-tumorigenic mechanisms known
      to promote HCC progression, indicating its potential as promising therapeutic
      agent that selectively affects cancer cells.

PMID- 20043080
TI  - Androgen regulated TRPM8 expression: a potential mRNA marker for metastatic
      prostate cancer detection in body fluids.
AB  - Identification of sensitive and specific biomarkers for early detection and
      prognosis of prostate cancer is essential for timely and appropriate treatment of
      the disease in individual patients. We identified an RNA transcript with sequence
      homology to TRPM8 (melastatin-related transient receptor potential member 8) that
      was overexpressed in tumor vs. patient-matched non-tumor prostate tissues by RT
      PCR differential display (DD). Semi-quantitative RT-PCR analysis revealed that
      TRPM8 levels were higher in tumor than in non-tumor tissue from 31 of 40 (>75%)
      patients examined. Overexpression of TRPM8 was independent of changes in androgen
      receptor (AR) mRNA levels in tumor tissue. However, in studies with established
      cell lines, TRPM8 expression was detectable only in AR-positive, but not in AR
      negative cells, and it was suppressed by steroid deprivation or anti-androgen
      bicalutamide (Casodex) treatment, suggesting the requirement of AR activity for
      TRPM8 expression in prostate cancer cells. TRPM8 mRNA was also detected in body
      fluids of men. Most importantly, its levels were significantly higher (p<0.001,
      n=18) in urine and blood of patients with metastatic disease than in those of
      healthy men. However, there was no significant difference (p>0.05, n=10) in its
      levels between prostate cancer patients with localized disease and healthy men.
      Together, these studies demonstrate that TRPM8 expression is androgen regulated
      in prostate cancer cells and that, while tissue TRPM8 mRNA levels can be used for
      detection of prostate cancer, urine and blood TRPM8 mRNA levels may prove to be
      useful for distinguishing metastatic disease from clinically localized prostate
      cancer at the time of diagnosis.

PMID- 20043081
TI  - Expression of estrogen receptor alpha with a Tet-off adenoviral system induces
      G0/G1 cell cycle arrest in SKBr3 breast cancer cells.
AB  - Endocrine therapies targeting estrogen action are pivotal for the prevention and
      treatment of ER-positive breast cancers. Previous studies sought to recreate
      hormone responsiveness by the stable expression of ERalpha in the ER-negative MDA
      MB-231 breast cancer cells. Paradoxically, estrogen inhibits breast cancer cell
      growth when an exogenous ERalpha is expressed. In this study, we have built on
      previous studies by developing a Tet-off adenoviral system to express ERalpha in
      the ER-negative SKBr3 breast cancer cells that over-express both EGFR and HER2.
      This system efficiently delivers ERalpha and the expression level of ERalpha is
      controlled by doxycycline in a concentration-dependent manner. The growth of
      SKBr3 was inhibited by ERalpha expression and further inhibited in the presence
      of 1 nM 17beta-estradiol. SKBr3 cells were arrested at G0/G1 cell cycle upon
      ERalpha expression, which corresponded to an increase of p21Cip1/Waf1, hypo
      phosphorylation of pRb and decrease of E2F1. Estrogen also reduced EGFR and HER2
      expression in SKBr3 cells after ERalpha was expressed. Given that estrogen
      induced increase of p21Cip1/Waf1 and decrease of E2F1 was also observed in MDA-MB
      231 cells stably transfected with ERalpha, our results suggest that a common
      pathway might be shared by different breast cancer cell lines whose growth is
      suppressed by ectopic ERalpha and estrogen.

PMID- 20043082
TI  - Regulation of heat shock protein 70-1 expression by androgen receptor and its
      signaling in human prostate cancer cells.
AB  - Heat shock protein (hsp) 70-1 (hsp70-1) is overexpressed in human prostate cancer
      cells and may play important roles in prostate cancer resistance to conventional
      therapies. The purpose of this study was to investigate whether androgen receptor
      (AR) and its signaling regulate hsp70-1 expression. Several lines of AR-positive
      (LNCaP, LAPC-4, and 22Rv1) and -negative (PC-3, DU145, WPE1-NB14 and WPE1-NB-26)
      human prostatic cells were used in the study. Dihydrotestosterone (DHT) enhanced
      hsp70-1 expression in LNCaP cells. Expression of hsp70-1 in LNCaP cells was
      downregulated by the anti-androgens bicalutamide (Bic), and flutamide (Flut), and
      a newly identified AR signaling antagonist DL3. The downregulation of hsp70-1 by
      DL3 was also observed in LAPC-4 and 22Rv1 cells, but not in the four lines of AR
      negative cells examined. Expression of hsp70-1 was also reduced by DL3 in PC-3
      cells engineered with AR. On the other hand, knocking down AR in LNCaP cells by
      siRNA moderately reduced hsp70-1 level and abolished effects of DL3 on hsp70-1
      expression. DL3 reduced hsp70-1 mRNA synthesis in cells and its in vitro gene
      transcription but did not significantly alter the stabilities of hsp70-1 mRNA and
      protein. Chromatin-immunoprecipitation (ChIP) assay showed that AR bound to the
      promoter region of HSPA1B gene, which was reduced in cells treated with DL3 or
      Bic. These data suggest that AR and its signaling regulate hsp70-1 expression in
      prostate cancer cells and that HSPA1B could be an AR target gene.

PMID- 20043083
TI  - Receptor and enzyme expression for prostanoid metabolism in colorectal cancer
      related to tumor tissue PGE2.
AB  - Prostaglandins support progression of colorectal cancer by several mechanisms.
      This conclusion is based on epidemiological and drug intervention long-term
      studies or retrieved from animal and cell culture experiments. The aim of the
      present study was to map receptor and enzyme expression for prostanoid metabolism
      in the presence of high or low PGE2 content within colon cancer tissue at primary
      tumor operation and after short-term preoperative provision of non-steroidal anti
      inflammatory drug (NSAID). Twenty-three unselected patients with colon cancer
      were randomly selected to receive indomethacin (NSAID) or sham treatment for 3
      days before surgery. Normal colon and tumor tissue were collected at operation
      for RNA extraction. Tissue PGE2 levels were measured by radioimmunoassay. Gene
      expression was quantified by microarray and real-time PCR. COX-1 expression
      increased proportionally to COX-2 expression in colon cancer tissue from
      untreated patients. Indomethacin reduced PGE2 content in normal and tumor tissue
      with subsequently decreased IP, HPGD and PPARgamma receptor expression in both
      tumor and normal colon tissue, while subtype EP1-4 receptors were not
      significantly influenced by indomethacin treatment. MPGES-1 expression was not
      related to overall PGE2 content in tumor and colon tissue, but decreased
      significantly in normal tissue during indomethacin exposure. Reduction of tumor
      tissue PGE2 was related to significant alteration in expression of several
      hundred genes indicating decreased cell cycling and increased apoptosis during
      indomethacin treatment, probably related to upregulation of acute phase reactants
      in tumor tissue. Increased prostanoid activity in colon cancer tissue is related
      to cross-talk between tumor and stroma cells.

PMID- 20043084
TI  - FBXL16 is a novel E2F1-regulated gene commonly upregulated in p16INK4A- and
      p14ARF-silenced HeLa cells.
AB  - Two crucial cell cycle regulators, p16INK4A and p14ARF, are produced from the
      cyclin-dependent kinase inhibitor 2A (CDKN2A) gene locus by alternative reading
      frames; these regulators act as tumor suppressors during tumorigenesis. However,
      the molecular events incidental to the acute functional loss of CDKN2A remain a
      critical issue. Two pivotal regulatory pathways of cell fate determination
      involving p16INK4A/retinoblastoma protein (pRb)/E2F1 and p14ARF/p53 interact
      tightly with each other; however, novel factors with an integral or overlapping
      role in these two pathways remain incompletely defined. To this end, we
      specifically decreased the expression of p16INK4A or p14ARF proteins using RNA
      interference (RNAi) in HeLa cells. Using a DNA microarray approach, we showed
      that several genes are commonly regulated in both p16INK4A and p14ARF knockdown
      cells, compared with control RNA-treated cells. We focused on the FBXL16 (F-box
      and leucine-rich repeat protein 16) gene, the expression of which was
      reproducibly upregulated in p16INK4A and p14ARF knockdown cells, as evaluated
      using RT-PCR. Interestingly, the promoter region of FBXL16 was shown to be
      upregulated by activator E2Fs. Finally, RNAi-mediated knockdown of FBXL16
      increased the cell proliferation rate of HeLa cells. Together, our results
      illustrate a unique aspect of the interdependence between the p16INK4A/pRb/E2F1
      and p14ARF/p53 pathways at a molecular level.

PMID- 20043085
TI  - Inhibition of glutathione-S-transferase as a treatment strategy for multidrug
      resistance in childhood rhabdomyosarcoma.
AB  - Multidrug resistance (MDR) is a common problem in the treatment of childhood
      rhabdomyosarcoma (RMS). A complete reversal of MDR is currently not possible. The
      aim of this study was to investigate the role of glutathione-S-transferase (GST)
      as mechanism of MDR in childhood RMS and to analyze possible reversal strategies.
      Female athymic mice underwent xenotransplantation with embryonal or alveolar RMS
      cells and were treated with vincristine. Gene expression analysis using
      Affymetrix HU-Gene 1.0 arrays revealed 2314 differentially expressed genes
      between the groups in alveolar RMS and 1387 in embryonal RMS. Ingenuity pathway
      analysis revealed a cluster of 5 overexpressed genes of the GST family in animals
      treated with vincristine, putative mediating the development of MDR. In order to
      analyze possible GST activity after chemotherapy with other commonly used drugs
      (doxorubicin, topotecan), cell culture experiments with alveolar and embryonal
      RMS cells were carried out. Specific GST activity was quantified using the
      clorodinitrobenzol conjugation with glutathione. Increased GST activity was found
      after incubation with cytotoxic agents in all cell lines. Highest induction of
      GST activity was found in embryonal RMS (up to 12-fold). After incubation with
      the GST inhibitors, tumor cell viability was decreased depending on the type of
      tumor cell and inhibitor used. We detected a novel mechanism for MDR in childhood
      RMS mediated via genes and proteins of the GST family. Reversal of these effects
      may be achieved by GST inhibitors in part. The GST family represents a promising
      target for further treatment strategies in childhood RMS.

PMID- 20043086
TI  - ErbB2-enhanced invasiveness of H-Ras MCF10A breast cells requires MMP-13 and uPA
      upregulation via p38 MAPK signaling.
AB  - Overexpression of ErbB2 has been frequently found in mammary carcinoma. We have
      previously shown that the aberrant activation of H-Ras induces human breast cell
      invasion and migration. The present study was aimed at investigating the effect
      of ErbB2 overexpression on H-Ras-induced breast cell invasion and to elucidate
      the underlying mechanisms. Herein, we show that overexpression of ErbB2 promotes
      invasive and migratory abilities of H-Ras-activated MCF10A human breast
      epithelial cells through upregulation of matrix metalloproteinase (MMP)-13 and
      urokinase-type plasminogen activator (uPA). We also demonstrate that the p38 MAPK
      is an important signaling molecule in the ErbB2-induced upregulation of MMP-13
      and uPA and invasion/migration of H-Ras MCF10A cells overexpressing ErbB2. The
      present study elucidating the molecular mechanism underlying ErbB2-induced
      promotion of H-Ras MCF10A cell invasion may provide invaluable information for
      understanding breast cancer progression and establishing therapeutic
      interventions for breast cancer.

PMID- 20043087
TI  - Overexpression of Cdx2 inhibits progression of gastric cancer in vitro.
AB  - The caudal-type homeobox gene Cdx2 encodes a transcription factor which in adult
      mammals is expressed in the cells of the intestinal epithelium and is thought to
      play an important role in their proliferation and differentiation. Cdx2 mediates
      apoptosis and suppresses tumorigenesis in many tissue types, but there are few
      data available on Cdx2 expression and its relationship to tumor kinetics in
      gastric cancer. To gain better insight into the involvement of Cdx2 in the
      biological characteristics of gastric cancer, we investigated the effect of Cdx2
      overexpression on the progression of gastric carcinoma cells. A gastric cancer
      cell line stably overexpressing Cdx2 (MGC-803/Cdx2) was established. The
      influence of Cdx2 overexpression on in vitro cell growth was assessed by
      measuring cell survival, colony formation and cell cycle progression. The results
      clearly showed that overexpression of Cdx2 significantly inhibited cell growth
      and proliferation, blocking entry into the S phase of the cell cycle. MGC
      803/Cdx2 cells also had a higher apoptotic rate than control cells. In addition,
      Cdx2 reduced the motility and invasion of gastric cancer cells. In summary, Cdx2
      overexpression can effectively inhibit gastric cancer progression and may be used
      as a potent therapy.

PMID- 20043088
TI  - Elevated expression of Ki-67 identifies aggressive prostate cancers but does not
      distinguish BRCA1 or BRCA2 mutation carriers.
AB  - Prostate cancers in men with germline BRCA1 and BRCA2 mutations are more
      aggressive than morphologically similar cancers in men without these mutations.
      This study was performed to test the hypothesis that enhanced expression of Ki
      67, as a surrogate of cell proliferation, is a characteristic feature of prostate
      cancers occurring in BRCA1 or BRCA2 mutation carriers. The study cohort comprised
      20 cases of prostate cancer in mutation carriers and 126 control sporadic
      prostate cancers. Of the combined sample cohort, 65.7% stained only within
      malignant tissues while 0.7% stained in both malignant and benign tissues
      (p<0.001). Significantly increased expression of Ki-67 occurred in prostate
      cancers with higher Gleason score (p<0.001). Elevated Ki-67 expression was
      identified in 71% of prostate cancers in BRCA1 or BRCA2 mutation carriers and in
      67% of the sporadic controls (p>0.5). Similar results were obtained when the data
      were analysed using a threshold set at 3.5 and 7.1%. This study shows that
      elevated expression of Ki-67 is associated both with aggressive prostate cancers
      and with high Gleason score irrespective of whether their occurrence is against a
      background of BRCA1 or BRCA2 mutations or as sporadic disease. The data suggest
      that, since elevated Ki-67 does not distinguish prostate cancers occurring in
      BRCA1 or BRCA2 mutation carriers from sporadic prostatic malignancies, the
      effects of these genetic mutations are probably independent. While all prostate
      cancers occurring in the presence of BRCA germline mutations are clinically
      aggressive, their potentially different phenotypes consistently involve maximal
      rates of cell proliferation.

PMID- 20043089
TI  - Aurora-A gene is frequently amplified in basal-like breast cancer.
AB  - Aurora-A is a serine-threonine kinase having vital cellular functions in mitosis
      and is a promising target for therapy in treating patients with cancer. This
      study assesses the clinicopathological associations of AURKA gene amplification
      in clinical breast tumors and association of gene copy number with its mRNA and
      protein expression in breast cancer cell lines. In this pilot study, we examined
      Aurora-A gene (AURKA) amplification in 126 clinical breast tumors by chromogenic
      in situ hybridisation (CISH). AURKA amplification (found in 21%) showed an
      association with basal-like tumor phenotype (p=0.046). A separate series of basal
      like breast tumors (n=26) provided further evidence of the importance of AURKA in
      these tumors. AURKA amplification status was associated with
      immunohistochemically detectable Aurora-A protein expression (p<0.0001). In
      breast cancer cell lines, gene amplification was strongly associated with high
      mRNA expression (p<0.0001). JIMT-1 cell line was found as a possible in vitro
      model system for testing Aurora-A inhibitors, since it has been classified as
      basal-like breast cancer and here it showed both AURKA gene amplification and
      elevated mRNA expression. AURKA gene amplification is a common genetic aberration
      in breast cancer, especially in tumors displaying basal-like phenotype. Thus,
      these patients might be suitable candidates for future targeted therapies with
      Aurora-A inhibitors.

PMID- 20043090
TI  - Concomitant expression of epithelial-mesenchymal transition biomarkers in breast
      ductal carcinoma: association with progression.
AB  - Epithelial to mesenchymal transition (EMT) is a process implicated in cancer
      progression in which the underlying cellular changes have been identified mainly
      using in vitro models. We determined the expression of some putative EMT
      biomarkers including E-cadherin, beta-catenin, zinc finger factor Snail (Snail),
      transforming growth factor beta1 (TGFbeta1), TGFbeta type II receptor (TBRII) and
      the HGF receptor (c-met) and their possible correlation to progression and
      overall survival in a series of breast ductal carcinoma in situ (DCIS) and
      invasive ductal carcinomas (IDC). Biomarkers were immunohistochemically
      determined in 55 IDC specimens from which 21 had lymph node metastases and in 95
      DCIS specimens, 46 of these cases associated to invasive carcinoma, in a tissue
      microarray (TMA). Positive cytoplasmic staining of TGFbeta1 (78.2%), c-met
      (43.6%), Snail (34.5%), TBRII (100%), membranous E-cadherin (74.5%) and
      membranous/cytoplasmic beta-catenin (71%) were detected in the IDC samples.
      Metastatic lymph node samples displayed similar frequencies. A significant
      increase of c-met and TGFbeta1 positivity along DCIS to IDC progression was noted
      but only TGFbeta1 positivity was associated with presence of lymph node
      metastases and advanced stages in IDC. The evaluation of the other EMT markers in
      DCIS did not show differences in positivity rate as compared to invasive
      carcinomas. DCIS either pure or associated to IDC showed similar expression of
      the analyzed biomarkers. All the carcinomas exhibited positive expression of
      TBRII. Associations between the markers, determined by Spearman's correlation
      coefficient, showed a significant association between TGFbeta1 and respectively E
      cadherin, beta-catenin and c-met in DCIS cases, but in invasive carcinomas only
      cadherin and catenin were positively correlated. Kaplan-Meier survival curves
      revealed that none of the EMT biomarkers analyzed were correlated with survival,
      which was significantly determined only by clinical and hormone receptor
      parameters.

PMID- 20043091
TI  - Expression and prognostic value of Id protein family in human breast carcinoma.
AB  - Inhibitors of DNA binding/inhibitors of differentiation (Id) protein family (Id
      1, -2, -3 and -4) of helix-loop-helix proteins have been shown to be involved in
      carcinogenesis and are regarded as prognostic markers in several types of human
      cancers. However, the roles of Id proteins during breast carcinoma progression
      remain unclear. The objective was to study the effects of Id proteins in breast
      cancer. The expression of Id-1, Id-2, Id-3 and Id-4 proteins was examined in 122
      dissected female human breast carcinoma tissues and 22 normal female breast
      specimens by immunohistochemical assay and the relationship between Id staining
      and clinical pathological characteristics of breast cancer was also analyzed. The
      over-expressed Id-1 and down-regulated Id-4 proteins were found both correlated
      with poorer differentiation and more aggressive behavior of the tumor. Id-1
      protein could be termed as a negative prognostic marker while Id-4 protein as a
      positive marker for patients with breast carcinoma. Although the differentially
      expressed Id-2 and -3 may be correlated with some clinical parameters, they could
      not be used as independent prognostic factors in human breast cancer.

PMID- 20043092
TI  - Nuclear 8-hydroxy-2'-deoxyguanosine as survival biomarker in patients with
      cutaneous melanoma.
AB  - 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the main mutagenic modifications
      induced in DNA by oxidative stress. Elevated levels of 8-OHdG have been regarded
      as an independent prognostic factor in different types of cancer. Various
      enzymes, such as human 8-oxoguanine DNA-glycosylase 1 (hOGG1) and glucose-6
      phosphate dehydrogenase (G6PD), act as protection against oxidative stress. The
      low activity of such enzymes has been consistently associated with increased risk
      of progression in several tumor types. The aim of this study was to investigate
      whether 8-OHdG, hOGG1 and G6PD expression in tumor tissues might be a predictor
      of survival in melanoma patients. The expression of 8-OHdG, hOGG1 and G6PD was
      immunohistochemically investigated in primary cutaneous melanoma and the effect
      on survival was analyzed. Furthermore, the immunostaining for p53 and survivin
      was evaluated and the relationship among 8-OHdG, hOGG1, G6PD, p53 and survivin
      expression was analyzed. Kaplan-Meier analysis demonstrated that patients with
      low expression of nuclear 8-OHdG had significantly longer survival time compared
      with those with a high expression (P=0.032), whereas cancer-specific survival of
      patients was not associated with hOGG1 or G6PD expression. These results suggest
      an involvement of oxidative DNA damage in the process of melanoma pathogenesis
      and demonstrate that 8-OHdG expression in nuclei of tumor cells could be useful
      as an early independent prognostic marker in patients with primary cutaneous
      melanoma.

PMID- 20043093
TI  - Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4
      nitroquinoline 1-oxide.
AB  - Transgenic rats carrying human c-Ha-ras proto-oncogene (Hras128 rats) have been
      shown to be highly susceptible to induction of tumors. We have found an early
      induction of tongue tumors in Hras128 rats treated with 4-nitroquinoline 1-oxide
      (4NQO). 4NQO was administered to the Hras128 and wild-type Sprague-Dawley (SD)
      rats for 4 and 8 weeks, respectively. The experiment was terminated at 14
      (Hras128 rats) and 28 (SD rats) weeks. Either during or after treatment with
      4NQO, dysplastic hyperplasia, papilloma and squamous cell carcinoma were found on
      the tongue of both Hras128 and wild-type rats, with a higher incidence and
      multiplicity in Hras128 rats. Treatment of the Hras128 rats with 4NQO
      significantly increased cell proliferation in the tumor compared to the control
      rats. In the tongue tumors of the Hras128 rats, there was a significant increase
      in the mRNA expression levels of cyclin D1 and COX2. To examine whether this
      experimental system is useful for screening of the candidate agents for cancer
      preventive effect, nimesulide, a selective COX2 inhibitor, was tested in the
      present model. Nimesulide significantly decreased total multiplicity of tongue
      lesions compared to the control rats. Treatment of Hras128 rats with nimesulide
      caused a significant decrease in the levels of mRNA expression of cyclin D1 and
      COX2 in the tumor. Therefore, the current 4NQO-induced Hras128 rat tongue
      carcinogenesis model provides a simple and rapid system for investigating
      carcinogenesis process and evaluating the effect of possible cancer preventive
      agents for human tongue cancer.

PMID- 20043094
TI  - STAT3 blockade with shRNA enhances radiosensitivity in Hep-2 human laryngeal
      squamous carcinoma cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is an oncogene
      aberrantly activated in many human tumors. We studied whether radiation combined
      with STAT3 siRNA enhances radiosensitivity of Hep-2 human laryngeal squamous
      carcinoma cells (Hep-2 cells). Firstly, STAT3 targeting recombinant plasmid was
      constructed. Hep-2 cells were transfected with expression vector of STAT3 siRNA
      using Lipofectamine 2000. Semiquantitive RT-PCR detected effective STAT3 mRNA
      down-regulation by STAT3 siRNA. Secondly, Hep-2 cells were radiated with
      different doses of gamma-rays after transfection with STAT3 small interference
      RNA (siRNA). MTT assay showed cell proliferation decreased significantly (P<0.05)
      after STAT3 siRNA transfection combined with radiation. Thirdly, flow cytometry
      (FCM) demonstrated that cell apoptosis of combined treatment group increased
      significantly (P<0.05) and exhibited time dependency after 6 Gy irradiation
      (P<0.05). Simultaneously, STAT3, p-STAT3, Bcl-2, VEGF, p53 protein levels
      decreased in Hep-2 cells, with positive correlations between level of p-STAT3 and
      levels of Bcl-2, VEGF, p53, respectively (r=0.974, 0.988, 0.976, all P<0.01).
      Above all, specific siRNA targeting STAT3 gene is able to enhance the
      radiosensitivity in Hep-2 cells by regulating expression of Bcl-2, VEGF and p53
      proteins.

PMID- 20043095
TI  - Antitumor effects of telomelysin in combination with paclitaxel or cisplatin on
      head and neck squamous cell carcinoma.
AB  - Telomelysin (OBP-301) is a telomerase-specific replication-component adenovirus.
      Telomelysin has a human telomerase reverse transcriptase (hTERT) promoter element
      which efficiently kills human cancer cells, but not normal cells. The present
      study investigated the correlation between the antitumor effect of telomelysin
      and mRNA expression of hTERT and coxsackievirus and adenovirus receptor (CAR) in
      head and neck squamous cell carcinoma (HNSCC) in vitro and whether telomelysin
      enhances the antitumor effect of paclitaxel or cisplatin, in vivo using a HNSCC
      xenograft model. We also determined the optimal order for combining telomelysin
      treatment and chemotherapy as concurrent treatment, telomelysin treatment first
      and chemotherapy later, chemotherapy first and telomelysin treatment later for
      achieving the best anticancer effect. The mRNA expression of hTERT and CAR genes
      was examined by quantitative RT-PCR in 17 HNSCC cell lines. There was no
      significant correlation between the growth inhibition of telomelysin (ID50 for
      day 3, 5 and 7) in vitro and mRNA expression levels of hTERT and CAR. Regarding
      the correlation between CAR expression and telomelysin ID50 for day 3, all cell
      lines that showed a relative amount of CAR/beta-actin mRNA >0.4 had a low
      telomelysin ID50. This may indicate that CAR expression contributes to the
      efficacy of adenovirus infection and the antitumor activity of telomelysin in
      early stages of treatment. In our in vivo study, combining telomelysin and
      paclitaxel had an additive effect regardless of treatment order. On the other
      hand, combining telomelysin and cisplatin had additive effect only when cisplatin
      treatment preceded telomelysin treatment. These results suggest that paclitaxel
      is considered innocuous for replication of telomelysin, however cisplatin may
      influence replication of telomelysin.

PMID- 20043096
TI  - Pancreatic cancer therapy with a novel pump for controlled drug release.
AB  - Enhancing antitumor activity and minimizing treatment side effects are important
      issues in cancer therapy. One method to deal with these issues is the utilization
      of a drug delivery system (DDS). In this study, we developed a novel drug
      administration pump, a mechanically controlled DDS (M-DDS). The antitumor
      activity of 5-fluorouracil (5-FU) (15 or 30 mg/kg/day) was evaluated in
      comparison with systemic intraperitoneal (i.p.) administration for 7 days in a
      rat model of human pancreatic cancer. The M-DDS was superior to i.p.
      administration in enhancing antitumor activity and also prolonging median
      survival from 69 to 85 days at the lower drug dose (15 mg/kg/day). In addition,
      toxicities in liver, kidney and spleen were found in animals receiving i.p.
      administration, whereas rats receiving M-DDS treatment did not show these
      toxicities. The concentration of 5-FU in tumors 1 day after the completion of
      treatment was considerably higher in rats receiving M-DDS treatment. These
      results suggest that this novel M-DDS may be a powerful tool for the treatment of
      pancreatic cancer in combination with conventional chemotherapeutic drugs,
      offering strong antitumor activity with fewer toxicities. This novel M-DDS,
      consisting of a control circuit and drug reservoir/pump unit, may be a useful
      tool for the treatment not only of pancreatic cancer but also of various other
      accessible cancers for which there is no effective treatment, such as bile-duct
      and brain tumors.

PMID- 20043097
TI  - Proteolipid protein 2 is associated with melanoma metastasis.
AB  - The metastasis of malignant tumor cells from the primary tumor to distant sites
      in the body is a complex process. To identify genes that may be essential for
      metastasis, we established poorly metastatic mouse melanoma cells, namely Y925F
      mutated FAK-transfected cells (Y925F cells), from the highly metastatic mouse
      melanoma cell line B16F10, and performed expression analyses. The expression of
      phospholipid protein 2 (PLP2) was markedly down-regulated in the Y925F cells. To
      elucidate the function of PLP2, we established melanoma cells overexpressing
      PLP2. We found that PLP2 enhanced proliferation, adhesion, invasion, and MMP-2
      secretion in vitro, and tumor metastasis in vivo. These results suggest that PLP2
      aids metastasis. Furthermore, we showed that PLP2 binds specifically to PI3K,
      thus activating Akt.

PMID- 20043098
TI  - Fibroblasts from Werner syndrome patients: cancer cells derived by experimental
      introduction of oncogenes maintain malignant properties despite entering crisis.
AB  - Werner syndrome (WS) results from defects in the gene encoding WRN RecQ helicase.
      WS fibroblasts undergo premature senescence in culture. Because cellular
      senescence is a tumor suppressor mechanism, we examined whether WS fibroblasts
      exhibited reduced tumorigenicity, in comparison to control cells, in a model of
      experimental conversion of normal human cells to cancer cells. The combination of
      oncogenic Ras (Ha-Ras(V12G)) and SV40 large T antigen (SV40 LT) causes human
      cells to acquire neoplastic properties in the absence of telomerase. We found
      that WS cells could also be converted to a tumorigenic state by these oncogenes,
      as evidenced by invasion and metastasis of cells implanted in immunodeficient
      mice. Ras/SV40 LT-expressing cells retained invasiveness and malignant properties
      even when cells reached crisis in tumors in vivo. High levels of gelatinase were
      found by an in situ assay in Ras/SV40 LT-expressing cells undergoing crisis. We
      conclude that, despite evidence of accelerated senescence in WS cells, there is
      no evidence that the absence of active WRN acts as a barrier to neoplastic
      transformation. Moreover, we find that tumorigenic human cells retain malignant
      properties of the cells as they approach and reach crisis.

PMID- 20043099
TI  - The cell toxicity effect of secalonic acid D on GH3 cells and the related
      mechanisms.
AB  - To investigate the anti-pituitary adenoma effect of secalonic acid D (SAD)
      extracting from marine microorganisms, we used MTT colorimetric method to
      evaluate the proliferation of GH3 cells treated by SAD, the time- and dose
      dependent effects and the value of IC50 were recorded. Hoechst staining, Tunel
      and flow cytometry methods were used to analyze the apoptosis rate of GH3 cells
      treated by SAD. Western blotting, RT-PCR and caspase inhibitor (Z-VAD-FMK) were
      used to investigate the possible mechanism of SAD induced apoptosis and the
      expression of growth hormone (GH). The results showed that SAD has a time- and
      dose-dependent effect on GH3 cells and the cytotoxic effect was mainly through
      apoptosis. The mechanisms were partly through the activity of caspase family and
      also G1/S phase block. In addition, SAD also can suppress the expression levels
      of growth hormone in GH3 cells, however, the RT-PCR results showed that the
      mechanism was not through changing the expression of GH mRNA. We concluded that
      SAD may be a potential anti-pituitary tumor drug and further in vivo studies
      should be performed.

PMID- 20043100
TI  - Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a
      reactive oxygen species-dependent mitochondrial signaling pathway.
AB  - Several studies have shown that curcumin can induce apoptosis and inhibit growth
      in human A549 lung adenocarcinoma cells. However, the mechanism is not completely
      understood yet. The present study was designed to investigate the effects of
      curcumin on A549 cells to better understand its apoptosis and apoptosis-related
      factors in vitro. The apoptosis induction, intracellular reactive oxygen species
      (ROS) and mitochondrial membrane potential (MMP) were examined by confocal
      fluorescence microscope and flow cytometry. The MAPK protein expression was
      examined by Western blot analysis. After treatment with curcumin, apoptosis were
      observed. Curcumin-induced apoptosis was accompanied by an increase of
      intracellular ROS level and a loss of MMP. In addition, induction of apoptosis
      was also accompanied by sustained phosphorylation and activation of JNK, p38 and
      ERK. However, pretreatment with MAPK inhibitors had no effect upon curcumin
      induced apoptosis. GSH and NAC, an anti-oxidant agent, blocked the curcumin
      induced ROS production, MMP loss and rescued cells from curcumin-induced
      apoptosis. Our results indicated that curcumin induced apoptosis in A549 cells
      through a reactive oxygen species-dependent mitochondrial signaling pathway and
      independent of MAPK signaling pathway.

PMID- 20043101
TI  - Phosphoproteomic profiling of arsenite-treated human small airway epithelial
      cells.
AB  - Arsenic is well documented as a chemotherapeutic agent capable of inducing cell
      death; however, it is also considered as a human carcinogen. Although it has
      recently been shown that arsenite exposure can potentiate genotoxicity, little is
      known about its global effects exerted in cells at the proteome level.
      Immortalized human small airway epithelial cells exposed to arsenite were used to
      identify phosphoproteins of two major signaling cascades, such as the human
      phospho-receptor tyrosine kinase (Phospho-RTK) and the mitogen-activated protein
      kinases (MAPKs). These two arrays included several phosphoproteins, such as EGFR,
      ErbB2, ErbB4, InsulinR, Flt-3, extracellular signal-regulated kinases (ERK1/2),
      intracellular kinases such as AKT, GSK-3, c-Jun N-terminal kinases (JNK1-3) and
      different p38 isoforms (alpha/beta/delta/gamma). In arsenite-treated cells,
      phosphorylation of EGFR, InsulinR and Flt3R showed an increase when compared to
      their non-arsenite treated counterparts. Inhibitors of these proteins further
      confirmed the involvement of such proteins in the neoplasm transformation of
      arsenite-treated human small airway epithelial cells as seen in changes in
      plating efficiency, anchorage-independent growth and proliferation rate. It can
      be concluded that analysis of phosphoprotein by using phosphoproteomic profiling
      can be very useful to understand the mechanism of arsenite-induced
      carcinogenesis.

PMID- 20043102
TI  - Chrysanthemum indicum ethanolic extract inhibits invasion of hepatocellular
      carcinoma via regulation of MMP/TIMP balance as therapeutic target.
AB  - Hepatocellular carcinoma (HCC) is an aggressive cancer with a dismal outcome
      largely due to metastasis and postsurgical recurrence. Thus, the inhibition of
      invasion and metastasis is of great importance in its therapies. Medicinal plants
      or ethnopharmacology used in folklore medicine continue to be an important source
      of discovery and development of novel or potential therapeutic agents for
      treatment of cancer. Chrysanthemum indicum, one of the medicinal plants or
      ethnopharmacology, is being used for treatment of many diseases including cancer.
      However, this plant molecular mechanisms underlining the anti-metastatic effects
      have not been well documented. In this study, Chrysanthemum indicum ethanolic
      extract (CIE) significantly suppressed proliferation and invasion of MHCC97H
      cells, one of the HCC cell lines with high metastatic potential, in a dose
      dependent manner. CIE markedly decreased MMP-2 and MMP-9 expression, increased
      simultaneously TIMP-1, and TIMP-2 expression further restoring their balance in
      the cancer cells. The present study indicates that CIE reduced MHCC97H cell
      metastatic capability, in part at least, through decrease of the MMP expression,
      simultaneous increase of the TIMP expression, further restoring their balance as
      therapeutic target in HCC. It is suggested that Chrysanthemum indicum is a
      potential novel therapeutic medicinal plant for treatment of HCC or cancer
      invasion and metastasis.

PMID- 20043103
TI  - Quantitative determination of HER2 expression by confocal microscopy assay in
      CTCs of breast cancer.
AB  - HER2 analysis in circulating tumor cells (CTCs) may have clinical significance
      for HER2-targeted therapy as HER2-positive CTCs and disseminated tumor cells can
      be detected in patients with HER2-negative primary tumors who currently do not
      have access to HER2-targeted therapy. In this study, we performed quantitative
      analysis by confocal microscopy assay for evaluation of HER2 expression in
      individual tumor cells. HER2 testing by confocal microscopy assay exhibited high
      concordance with results of real-time PCR, Western blot analysis and FISH
      analysis. We found that there was a significant positive correlation between HER2
      overexpression and gene amplification in individual CTCs, which provided
      validation of confocal microscopy assay for HER2 expression in CTCs. By using
      subsets of 10 consecutive cells (bins), we conclude that HER2 expression (3+) in
      CTCs predicts HER2 overexpression of tumor with high probability in breast cancer
      patients. These results may provide interpretive guidelines for HER2 status assay
      in CTCs and raise great opportunities for using CTCs as non-invasive and 'real
      time' biopsy to examine and monitor the status of tumor markers.

PMID- 20043104
TI  - Expression of alpha-, beta- and gamma-synuclein in colorectal cancer, and
      potential clinical significance in progression of the disease.
AB  - The synucleins (alpha-, beta- and gamma-synuclein) are a small, soluble, highly
      conserved group of neuronal proteins that attracted considerable attention due to
      their involvement in both neurodegenerative diseases and cancer. In this study,
      we examined the synuclein exprsssion in colorectal cancer (CRC) tissues, tumor
      matched non-neoplastic adjacent tissues (NNAT), and CRC cell lines, and then
      investigated clinical significance of synucleins. By using semi-quantitative RT
      PCR, synuclein mRNA expression was detected in eight CRC cell lines. It was much
      higher in CRC samples than in NNAT samples (P<0.05). The results of western
      blotting showed that the levels of synucleins protein expression in CRC cells
      approximately corresponded to the levels of synuclein mRNA expression.
      Immunohistochemical staining revealed that gamma-synuclein protein expression was
      up-regulated in CRC samples compared to NNAT samples (P=0.022), and was
      significantly correlated with clinical stage and lymph node involvement of CRC
      (P<0.05). Although, there was no significant difference in either alpha- or beta
      synuclein protein expression between tumor and normal samples (P>0.05), often
      more than one form of synuclein was expressed in a tumor sample. More ratios of
      later stage and lymph node-positive tumors expressed a least one type of
      synuclein protein, and more ratios showed positive for either alpha or gamma
      synuclein expression, as well as positive either for beta or gamma-synuclein in
      more ratios of lymph node-positive tumors. These results show that alpha-, beta-
      and gamma-synuclein are expressed in a high percentage of CRC. gamma-synuclein
      protein is valuable for evaluation of progression of CRC, and it is more
      sensitive to predict advanced stage and lymph node invasion by detection of gamma
      synuclein protein combined with either alpha- or beta-synuclein protein or both
      than by detection of gamma-synuclein only.

PMID- 20043105
TI  - Gastrointestinal stromal tumor and other primary metachronous or synchronous
      neoplasms as a suspicion criterion for syndromic setting.
AB  - Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although
      KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic
      and inherited GISTs, a small subset of GISTs are negative for both. Besides the
      classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic
      disease. The present study was designed to analyze the synchronous and
      metachronous tumors developed among GIST patients assessed by our institution for
      GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and
      64 women) were recruited between 1988 and 2007 and their clinical and
      pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR
      genes was performed on somatic and peripheral blood DNA. GISTs occurred
      associated with other primary malignancies in 46 of 141 (32.6%) patients. The
      most common neoplasms were gastrointestinal and genitourinary. A novel exon 6
      germline large deletion of NF1 was identified in the NF1/GIST kindred. The
      development of GIST associated with other neoplasms is common and diagnosis of
      peculiar benign associated-neoplasms warrants the search for familial cancer
      susceptibility. In particular, syndromic or familial settings have to be
      suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA
      negative GIST patients.

PMID- 20043106
TI  - Analysis of loss of heterozygosity on chromosome 4q in hepatocellular carcinoma
      using high-throughput SNP array.
AB  - To identify tumour suppressor genes (TSGs) associated with hepatocellular
      carcinoma (HCC) on chromosome 4q using a high-throughput single nucleotide
      polymorphism (SNP) array, we first scanned for loss of heterozygosity (LOH) of 40
      SNPs on chromosome 4q and discovered 2 hot regions: 4q24-26 and 4q34.3-35. We
      then further scanned for LOH of 338 SNPs in genes around 4q34.3-35 and discovered
      3 genes with the most frequent LOH: nei endonuclease VIII-like 3 (NEIL3),
      interferon regulatory factor 2 (IRF2) and inhibitor of growth family member 2
      (ING2). A review of the literature indicates only ING2 might be a TSG associated
      with HCC.

PMID- 20043107
TI  - Expression of endothelin receptor subtypes in bronchial tumors.
AB  - The importance of endothelin-1 (ET-1) in cell growth, migration and stimulation
      of angiogenesis suggests that ET-1 may play a role in tumor progression. The
      expression of the ET-1 receptors ETA (ET(A)R) and ETB (ET(B)R) was analyzed by
      immunohistochemistry in fragments of human lung carcinomas. Samples were obtained
      from 11 patients with adenocarcinoma (ADK), 12 with squamous cell carcinoma (SCC)
      and 8 patients with small cell carcinoma (SCLC). Morphologically normal airway
      areas adjacent to the tumors served as controls. ADK and SCC samples had ET(A)R
      and ET(B)R levels similar to normal tissues; however, the ET(A)R/ET(B)R ratio was
      higher in ADK than in SCC. We also observed the presence of endothelin receptors
      in SCLC, although the ET(A)R levels and the ratio ET(A)R/ET(B)R were lower than
      in normal tissue and in other carcinomas. In conclusion, both ET(A)R and ET(B)R
      are present in lung carcinomas but at different levels, according to the
      histological type of tumor.

PMID- 20043108
TI  - Primary prostate cancer cultures are models for androgen-independent transit
      amplifying cells.
AB  - Numerous efforts exist for developing primary prostate cancer cultures for
      studying the biology of this tumor entity and for evaluation of the effectiveness
      of novel therapies. However, there is doubt if cultures that represent the fully
      differentiated phenotype can be established. The aim of the present study was to
      characterize primary outgrowing prostate epithelial cells due to their basal or
      luminal characteristics and their potential for serving as androgen-responsible
      model. From fresh prostate cancer radical prostatectomy specimens, pieces of
      approximately 2-4 mm diameter were placed on top of transwell culture chambers,
      which were coated with matrigel and cultured in prostate epithelial selection
      medium with 10% fetal calf serum. The monolayer of outgrowing cells was incubated
      with a physiological concentration of 1 nM dihydrotestosterone (DHT). One group
      was additionally cultivated without DHT and another group was treated with the 5
      alpha-reductase-inbitors MK-368 and MK-905. From the monolayer of the outgrowing
      cells, RNA was isolated and the expression of androgen receptor (AR), prostate
      specific antigen (PSA), Kallikrein 2 (KlK2), prostate-specific membrane antigen
      (PSMA), and prostate stem cell antigen (PSCA), cytokeratin (CK)5, and CK18 was
      determined by realtime quantitative PCR. The outgrowing cells from the prostate
      cancer tissue pieces could be characterized as epithelial cells with basal and
      transit amplifying characteristics as shown by co-expression of CK5 and CK18. In
      all cultures, a very low expression of the luminal cell marker genes AR, PSA and
      KLK2 was measured. The levels of PSCA were clearly higher with a broad variation.
      Upon cultivation without DHT or treatment with alpha-reductase inhibitors no
      regulation of AR, PSA and KlK2 was found. Due to the co-expression of basal and
      luminal marker genes, primary prostate cancer cultures can be charaterized as
      models of transit amplifying cells of the prostatic epithelium. They do not
      represent the differentiated secretory androgen-responsive cell phenotype.

PMID- 20043109
TI  - Is the resistance of gemcitabine for pancreatic cancer settled only by
      overexpression of deoxycytidine kinase?
AB  - The prognosis of pancreatic cancer remains poor, and the standard first-line
      chemotherapy with gemcitabine (GEM) has a response rate of less than 20%. Since
      expression of deoxycytidine kinase (dCK) seems important for improvement of GEM
      sensitivity, overexpression of dCK was investigated using pancreatic cancer cell
      lines (Panc-1, MIAPaCa-2 and BxPC-3). dCK gene was introduced into the cell lines
      by retrovirus and changes in IC50 were examined. Sensitivity of two pancreatic
      cancer cell lines to GEM elevated dramatically in comparison with control cells,
      but change of sensitivity remained at 1.8 times in BxPC-3. Since addition of
      tetrahydro uridine (THU), an inhibitor of deoxycytidine deaminase (CDA),
      increased the sensitivity 54-fold, overexpression of CDA seems to be the
      mechanism for improvement of the sensitivity. In conclusion, dCK is a key enzyme
      of GEM, but resistance of GEM is not improved in all pancreatic cancer cells by
      overexpression of dCK. Combination treatment based on expression of GEM
      metabolism-related gene may become an effective therapy in the future.

PMID- 20043110
TI  - Induction of apoptosis by the angucyclinone antibiotic chemomicin in human tumor
      cells.
AB  - Chemomicin (CHM), an angucyclinone antibiotic extracted from the fermentation
      broth of Nocardia Mediterranei subsp. Kanglensis 1747-64, shows immunosuppressive
      activity. However, whether it can inhibit growth of tumor cells remains elusive.
      In the present study, we show that CHM potently inhibited the proliferations of
      eight various types of human tumor cell lines and non-cross resistant to
      multidrug-resistant cells. In contrast to action of doxorubicin, the generation
      of reactive oxygen species was observed as early as 30 min after addition of CHM
      and its process did not involve iron. The apoptotic cells with chromatin
      condensation and Annexin V staining markedly increased after the human hepatoma
      HepG2 was exposed to 1, or 2 microg/ml CHM for 24 h. In the CHM-induced
      apoptosis, robust increment of p53 expression, activation of caspase-3, -7, -8, 
      9, cleavage of PARP and the phosphorylation of p38 and JNK, were detected by
      Western blot analysis. Further investigation revealed the disruption of
      mitochondrial membrane potential in the cells with CHM incubation for 4 h. Taken
      together, the results demonstrated that potent proliferation inhibitory effect of
      CHM on tumor cells is due to activation of the apoptotic pathway.

PMID- 20043111
TI  - Expression of neural stem cell markers in malignant rhabdoid tumor cell lines.
AB  - Malignant rhabdoid tumor (MRT) is considered to display multi-phenotypic
      characteristics but the true origin of this tumor remains unknown. In recent
      years, the concept of the cancer stem cell (CSC) has drawn great attention. In
      the present study we investigated six MRT cell lines (TM87-16, STM91-01, TTC642,
      TTC549, YAM-RTK-1 and TTC1240), for CD133, nestin and Musashi-1 (Msi-1), which
      are considered to be CSC as well as neural stem cell (NSC) markers, using assays
      for cell viability and apoptosis, reverse transcriptional polymerase chain
      reaction (RT-PCR), semi-quantitative PCR and Western blot analysis before and
      after differentiation-induction with N-(4-hydroxyphenyl) retinamid (4-HPR).
      Before differentiation-induction with 4-HPR, CD133 was detected in three MRT cell
      lines, nestin in three cell lines and Msi-1 in five cell lines. In TTC549 after
      differentiation-induction with 4-HPR, nestin and Msi-1 were down-regulated in a
      time-dependent manner. Similar down-regulation of Msi-1 was recognized in YAM-RTK
      1. In STM91-01, CD133 was gradually down-regulated and Msi-1 was down-regulated
      after a transient increase. Results from our study indicated that 4-HPR might be
      effective in some MRTs. Expression of NSC markers showed that some MRTs contain a
      subpopulation of NSC and down-regulation of NSC markers in MRT cells provides
      supportive evidence that many MRTs could be considered of neuroectodermal origin.

PMID- 20043112
TI  - Modified technique for determining therapeutic response to radiofrequency
      ablation therapy for hepatocellular carcinoma using US-volume system.
AB  - In radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), microbubbles
      appearing during the procedure make it difficult to determine effectiveness with
      ultrasonography (US) imaging. We developed a modified US-volume system and
      evaluated its efficacy for demonstrating response to therapeutic RFA. Our US
      volume system displays multiplanar reconstruction (MPR) images providing a
      synchronized view with a US image along with past US-volume data in real-time
      side-by-side on a personal computer. Seventy-eight patients (94 nodules) were
      enrolled, of whom 35 (47 nodules) were evaluated using this system (US-volume
      group) and compared to the other 43 (47 nodules) examined before development of
      our system (control group). All nodules were clearly depicted by US. If the
      shortage of margin was predicted with US-volume system, we performed additional
      needle insertion. Tumor necrosis following RFA was graded by dynamic computed
      tomography as follows: Grade A, necrotic area surrounded in all directions with
      an adequate margin (>or=5 mm); Grade B, necrotic area surrounded in all
      directions, though some margin areas <5 mm; and Grade C, residual tumor or
      necrotic area smaller than the target tumor. In the US-volume group, the average
      tumor size was not smaller than that in the control (15.9+/-4.9 vs. 16.0+/-4.3
      mm) and adequate margins were obtained (Grade A, B, C, 45/1/1 vs. 35/8/4;
      P<0.01). Further, there was a significant reduction in numbers of RFA sessions as
      compared to the control (1.03+/-0.17 vs. 1.12+/-0.32; P<0.01). In HCC patients
      undergoing RFA, our modified US-volume system accurately demonstrated therapeutic
      response, which led to a reduced number of RFA sessions.

PMID- 20043113
TI  - A new high-performance liquid chromatography method determines low production of
      9-beta-D-arabinofuranosylguanine triphosphate, an active metabolite of
      nelarabine, in adult T-cell leukemia cells.
AB  - The 9-beta-D-arabinofuranosylguanine (ara-G), an active compound of nelarabine,
      demonstrates potent cytotoxicity specifically on T-cell malignancies. In cells,
      ara-G is phosphorylated to ara-G triphosphate (ara-GTP), which is subsequently
      incorporated into DNA, thereby inhibiting DNA synthesis. Because ara-GTP is
      crucial to ara-G's cytotoxicity, the determination of ara-GTP production in
      cancer cells is informative for optimizing nelarabine administration. Here, we
      developed a new, sensitive isocratic-elution HPLC method for quantifying ara-GTP.
      Samples were eluted isocratically by using phosphate buffer at a constant flow
      rate. Ara-GTP was clearly separated from other nucleotides by using an anion
      exchange column and it was quantitated by its peak area at 254 nm. The standard
      curve was linear with low variability and a sensitive detection limit (10 pmol).
      Furthermore, due to ara-G's specificity to T-cells we hypothesized that
      nelarabine might be effective against adult T-cell leukemia (ATL). The ara-GTP
      production was compared between T-lymphoblastic leukemia CCRF-CEM and ATL cell
      lines in vitro. When CEM cells were incubated with ara-G, the ara-GTP production
      increased in a concentration- and time-dependent manner. In contrast, 5 ATL cell
      lines accumulated lower ara-GTP in the same condition. While ara-G inhibited the
      growth of CEM cells with a 50% growth inhibition concentration of 2 microM, the
      inhibitory-concentration values were >1 mM in 8 of the 12 ATL cell lines. This
      ineffectiveness appeared to correspond with the low ara-GTP production. The
      present study is the first to evaluate the potential of ara-G against ATL cells;
      our results suggest that nelarabine would not be effective against ATL.

PMID- 20043114
TI  - ATP11A is a novel predictive marker for metachronous metastasis of colorectal
      cancer.
AB  - The adenosine triphosphate-binding cassette transporter-homologous gene ATP11A
      belongs to an extended family of adenosine triphosphate-binding cassette
      transporters. We analysed the ATP11A gene in 7 colorectal cancer cell lines and
      95 paired cases of colorectal cancer and non-cancerous regions to demonstrate the
      importance of ATP11A expression in colorectal cancer prognosis. ATP11A was
      expressed in the 7 colorectal cancer cell lines. ATP11A mRNA expression was
      higher in colorectal cancer tissue than in corresponding normal tissue (P<0.001).
      Patients with high ATP11A expression showed a poorer disease-free survival rate
      compared to those with low expression (P<0.001), thus indicating that increase in
      ATP11A expression was an independent predictor of metachronous metastasis of
      colorectal cancer. The present study suggests that ATP11A is a useful predictive
      marker of metastasis in colorectal cancer patients.

PMID- 20043115
TI  - Long-term administration of aspirin inhibits tumour formation and triggers anti
      neoplastic molecular changes in a pre-clinical model of colon carcinogenesis.
AB  - Despite numerous studies aimed at verifying the anti-tumour activity of aspirin
      on colon carcinogenesis little is known on the molecular targets involved in the
      anti-carcinogenic properties of this drug. We investigated the long-term
      administration of low dose of aspirin in a model of experimental colon
      carcinogenesis in rats. Adult Wistar rats received an intraperitoneal injection
      of azoxymethane (AOM) once a week for two weeks in order to initiate colon
      carcinogenesis. One week after AOM injection, rats received daily 0.01% aspirin
      (6 mg/kg body weight) in drinking water for 10 months. Compared to AOM control
      rats, aspirin treatment for 10 months caused a 50% reduction of the number of
      aberrant crypt foci associated with a 50% reduction of prostaglandin E2 (PGE2)
      concentration and suppressed by 80% tumour formation in the colon. RT-PCR
      quantitative analysis showed that aspirin treatment reduced significantly
      (P<0.01) the AOM-triggered increase in mRNA levels of soluble inflammatory
      mediators (TNFalpha and IL-1beta) and metalloproteinases (MMP3 and MMP7).
      Conversely, we detected an increased expression level of alpha-defensin-5 (Rd-5,
      2 fold) and lipocalin-2 (LCN2, 4 fold), two markers of the innate immunity
      system. The expression of apoptosis-related genes such as death receptors and
      their ligands were reduced by aspirin and the Bcl-2/Bax transcript ratio droped,
      Bcl-2 expression being reduced to the level found in saline control rats. The
      present study identifies new molecular targets triggered by aspirin in the
      colonic mucosa and may support the use of non-toxic low dose of aspirin in long
      term treatments as a prophylactic approach against colon carcinogenesis.

PMID- 20043116
TI  - Identification of a 0.4 Kb deletion region in 10q26 associated with endometrial
      carcinoma.
AB  - We have identified an allelic deletion common region in the q26 region of
      chromosome 10 in endometrial carcinomas, which has been reported previously as a
      potential target of genetic alterations related to this neoplasia. An
      allelotyping analysis of 19 pairs of tumoral and non-tumoral samples was
      accomplished using seven microsatellite polymorphic markers mapping in the 10q26
      chromosomal region. Loss of heterozygosity for one or more loci was detected in
      29% of the endometrial carcinoma samples. The observed pattern of loss enabled
      the identification of a 3.5 Mb common deleted region located between the D10S587
      and D10S186 markers. An additional result from an endometrial sample with
      evidence of a RER phenotype may suggest a more centromeric region of loss within
      the above-mentioned interval. This 401.84 Kb interval flanked by the D10S587 and
      D10S216 markers may be a plausible location for a putative suppressor gene
      involved in early stage endometrial carcinogenesis.

PMID- 20043117
TI  - The SNAIL family member SCRATCH1 is not expressed in human tumors.
AB  - The SNAIL and SLUG transcription factors play important roles in embryogenesis
      owing to their anti-apoptotic properties and their ability to promote
      morphogenetic changes by inducing epithelial-mesenchymal transitions (EMT). These
      characteristics provide many of the proteins in these families with oncogenic and
      pro-metastatic capabilities when reactivated in cancers. The SCRATCH subgroup of
      the SNAIL superfamily, including SCRATCH1 and SCRATCH2, display distinct
      embryonic functions and diverge early in evolution. Despite the described
      overexpression of SCRT1 (encoding for SCRATCH1) in a small subset of human lung
      cancers, there is little data supporting a role of SCRATCH proteins in
      tumorigenesis. To further explore this possibility, we assessed SNAI1 (SNAIL),
      SNAI2 (SLUG) and SCRT1 (SCRATCH1) expression in a wide panel of human and murine
      tumors encompassing 151 primary tumors and 6 different cancer types, including
      melanomas and multiple different carcinomas. Whereas SNAI1 and SNAI2 are widely
      expressed in human and murine tumors, our results reveal that SCRT1 transcripts
      are undetectable in nearly all of the examined tumors suggesting that SCRATCH1
      plays a minor role, if any, in tumorigenesis. Our data therefore suggest that
      oncogenic properties are not shared by all SNAIL superfamily members but instead
      are specifically allotted to the SNAIL subgroup supporting the conclusions that
      SNAIL and SCRATCH subgroups are functionally divergent and strengthening the
      hypothesis that the oncogenic potential of SNAIL and SLUG proteins relies on the
      hijacking of their embryonic functions.

PMID- 20043118
TI  - Mitochondrial NADH-dehydrogenase polymorphisms as sporadic breast cancer risk
      factor.
AB  - Breast cancer is the most frequently diagnosed female cancer all over the world.
      Although the molecular genetics of this disease has been the focus of many
      projects for over 20 years, the number of prognostic markers used in clinics is
      still unsatisfactory. Mitochondrial DNA mutations have been reported in many
      breast cancer studies. To investigate the possible role of mitochondrial
      inherited polymorphisms in breast cancer development we analyzed the sequence of
      NADH-dehydrogenase genes in cancer samples and their corresponding normal
      tissues. We detected increased incidence of mtDNA polymorphisms, in particular
      very rare polymorphisms such as A4727G, G9947A, A10044G, A10283G, T11233C, and
      C11503T. Our report supports the notion that mtDNA polymorphisms establish a
      specific genetic background for breast cancer development and that mtDNA analysis
      may help in selection of cohorts that should undergo intensive screening and
      early detection programs.

PMID- 20043119
TI  - PGF isoforms, PLGF-1 and PGF-2 and the PGF receptor, neuropilin, in human breast
      cancer: prognostic significance.
AB  - Placenta growth factor (PLGF) is a member of the vascular endothelial growth
      factor (VEGF) family, a group of angiogenic growth factors. Recently, isoforms
      have been identified. This study examined PLGF-1, PGF-2 and its receptor
      neuropilin-1 levels in human breast cancer in relation to patient's clinical
      parameters and how changes in expression may be linked to prognosis of the
      disease. PLGF-1, PGF-2 and neuropilin-1 transcript expression and distribution
      were examined quantitatively using real-time quantitative polymerase chain
      reaction (Q-PCR) on a cohort of human breast cancer (n=114) and background breast
      tissue (n=30) with a 10-year follow-up. Protein expression was assessed by an
      immunohistochemical method. We demonstrate that PLGF-1 transcript levels were
      significantly elevated when comparing tumours from patients with poor outcome and
      patients who remained disease-free (P=0.03), indicating a potential prognostic
      value. Immunohistochemistry demonstrated a marked increased in PGF-2 expression
      in tumour section compared with normal tissues (P<0.05). PGF-2 transcripts,
      showed little change in expression between tumour and background. High levels of
      PLGF-1 and PGF-2 were seen in ERbeta-negative breast tumour tissues. Neuropilin
      transcript was below detection in substantial portion of the samples and was more
      frequently detected in high grade tumours (P=0.008 vs. low grade) and in tumours
      from patients who died of breast cancer (P<0.001 vs. those who remained disease
      free). Our study shows that PLGF isoforms PLGF-1 and PGF-2 and indeed their
      receptor neuopilin, have an aberrant pattern of expression and that high levels
      of the PLGF-1 and neuropilin are linked to a poor prognosis.

PMID- 20043121
TI  - Microsatellite instability at tetranucleotide repeats in sporadic colorectal
      cancer in Japan.
AB  - Most tumors of patients with Lynch syndrome and a fraction of sporadic colorectal
      cancers (CRCs) exhibit high levels of microsatellite instability (MSI) at mono-
      and dinucleotide repeat loci. A different type of instability, elevated
      microsatellite alterations at selected tetranucleotide repeats (EMAST) has been
      found in non-colonic cancers. Our previous study demonstrated that EMAST is
      common in sporadic CRC. Here, we focused on the relationships between EMAST and
      other genomic instability parameters or clinicopathological features in an
      unselected series of 88 sporadic CRCs. Of the tumors in the sample, 4 (4.5%) were
      MSI-high (MSI-H), 9 (10.2%) were MSI-low (MSI-L) and 75 (85.2%) were
      microsatellite stable. EMAST status was determined using 7 EMAST markers. Fifty
      three (60.2%) tumors without MSI-H showed instability at >or=1 EMAST loci. All 4
      MSI-H tumors showed instability at several EMAST loci. Instability profiles of
      MSI-H tumors at EMAST loci were more complex than those of non-MSI-H tumors. A
      tendency of positive association was observed between MSI-L and EMAST (P=0.023).
      The frequency of loss of heterozygosity (LOH) for the 14 loci in EMAST-positive
      tumors was significantly higher than negative tumors (P=0.048). Among the
      clinicopathological parameters, only tumor location at the distal colon was
      associated with EMAST-negative tumors (P=0.0084, one-tailed). A relatively higher
      frequency of well-differentiated adenocarcinomas was observed in EMAST tumors as
      opposed to non-EMAST tumors, though the survival rate was similar. These results
      suggest that overlapping mechanisms that cause MSI-L, EMAST and LOH in CRCs may
      exist.

PMID- 20043120
TI  - Fusion induced reversal of dendritic cell maturation: an altered expression of
      inflammatory chemokine and chemokine receptors in dendritomas.
AB  - Dendritic cell-mediated cancer immunotherapy employs several ways to engage tumor
      antigens. We have demonstrated in both pre-clinical animal studies and early
      clinical trials that dendritomas, highly purified hybrids between dendritic cells
      (DC) and tumor cells, are superior activators of anti-tumor immunity. It has been
      argued, however, that DC vaccines may be dysfunctional in lymph node migration.
      In the present study we examined inflammatory chemokine and chemokine receptor
      expression as well as other maturation induced genes in dendritomas produced from
      either immature or mature DCs in order to shed light on their capacity to migrate
      from injection sites to draining lymph nodes and elicit an appropriate immune
      response. RNA microarray analysis was used to identify gene expression profiles
      for inflammatory chemokines and receptors and other maturation induced genes
      within dendritomas, lysate-pulsed dendritic cells, immature DCs and mature DCs.
      Gene regulation was confirmed with relative quantification, real-time RT-PCR in a
      separate experiment. We found that fusion of immature DCs to tumor cells
      initiates maturation with respect to inflammatory chemokines, chemokine receptors
      and other maturation induced genes in a similar pattern as LPS matured DCs.
      Interestingly, we saw a reversed gene profile when mature DCs were fused to tumor
      cells. LPS matured DCs displayed the chemokine repertoire expected with DC
      maturation; however, once fused to tumor cells, these chemokines and other
      maturation induced genes reverted to levels comparable to immature DCs. It
      appears that mature DCs used for dendritoma production result in a de-mature
      genotype. Our results indicate that dendritomas from immature DC/tumor cell
      fusions may be more effective in migration from injection site to draining lymph
      nodes and, therefore, would be more effective in stimulating anti-tumor immunity.

PMID- 20043122
TI  - EphA1 receptor silencing by small interfering RNA has antiangiogenic and
      antitumor efficacy in hepatocellular carcinoma.
AB  - The Eph family of receptor tyrosine kinases has emerged as one of the pivotal
      regulators of tumor angiogenesis. EphA1, the first identified member of the Eph
      receptor family, has been found to be overexpressed in several types of human
      tumors. A recent report indicated that EphA1 was overexpressed in hepatocellular
      carcinoma (HCC) and that elevated expression of EphA1 can promote proliferation
      of HCC cells through stimulation by exogenous Ephrin-A1. To investigate the role
      of EphA1 in angiogenesis and progression of HCC, we down-regulated EphA1 by RNA
      interference (RNAi) technology, in an HCC-derived cell line with a high level of
      EphA1 expression. We established a stable knockdown clone named SiEphA1/Huh-7.
      The knockdown resulted in decreased proliferation of Huh-7 cells, as well as
      decreased motility and invasion capability in vitro. siRNA-based EphA1 knockdown
      also down-regulated the expression of vascular endothelial growth factor (VEGF)
      and matrix metalloproteinase (MMP)-2 and -9. Interestingly, the suppression of
      EphA1 expression in Huh-7 cells reduced their outgrowth when inoculated in the
      subcutaneous space in the flank of nude mice, presumably through angiogenesis
      inhibition since microvessel density was found to be inhibited.

PMID- 20043123
TI  - Prediction of late normal tissue complications in RT treated gynaecological
      cancer patients: potential of the gamma-H2AX foci assay and association with
      chromosomal radiosensitivity.
AB  - In the present study, the gamma-H2AX assay was investigated as a predictive test
      for the development of late normal tissue complications. Therefore,
      phosphorylated histone H2AX (gamma-H2AX) foci were scored in peripheral blood T
      lymphocytes of gynaecological radiotherapy patients, irradiated in vitro with a
      high dose rate (HDR) and a low dose rate (LDR) protocol. The G2 chromatid break
      assay was used to compare chromosomal radiation sensitivity with DNA double
      strand-break (DSB) repair capacity. Late normal tissue reactions were scored
      according to the Common Terminology Criteria for Adverse Events (CTCAE) version
      3.0 scale. In our analyses, no differences in foci kinetics were found between
      the non to mild and moderate to severe patient groups after HDR irradiation.
      Furthermore, no relation was observed between the level of residual gamma-H2AX
      foci and CTC score after LDR irradiation. On the contrary, the number of
      chromatid breaks was associated with late clinical radiation sensitivity.
      Comparison of G2 chromatid break assay data with the residual number of radiation
      induced foci after LDR irradiation and repair times after HDR irradiation showed
      no relationship between the assays. From this study we can conclude that scoring
      of gamma-H2AX foci after in vitro irradiation of isolated T-lymphocytes of
      patients is not predictive for late radiotoxicity. This applies as well to the
      assessment of the repair kinetics after an HDR dose as to the determination of
      the number of residual foci after a LDR dose.

PMID- 20043124
TI  - Prognostic value of CA 125 in ovarian cyst fluid of patients with epithelial
      ovarian cancer.
AB  - Most ovarian tumors contain ovarian cyst fluid (oCF) which can be easily obtained
      during surgery. This is the first study that explored if CA 125 in oCF could be
      of prognostic value for patients with epithelial ovarian cancer (EOC). Of 54
      patients with primary EOC, oCF and preoperative serum were collected and
      clinicopathological data were retrospectively obtained. CA 125 was measured with
      the commercially available CA 125 assay. CA 125 in oCF (n=54, median: 55,500
      U/ml, range: 590-10,200,000 U/ml) was always higher than in the corresponding
      serum (n=51, median: 179 U/ml, range: 13-11,000 U/ml) (p<0.001) and values were
      moderately correlated (R=0.337, p=0.016). CA 125 in oCF was associated with
      histology (p<0.001) and tumor grade (p=0.038). High levels of oCF CA 125
      (>median) were significantly associated with a poor disease-free survival (DFS)
      (log-rank p=0.002 and p=0.005 univariate Cox-regression). Other factors
      associated with a poor DFS in univariate analysis were advanced FIGO stage,
      suboptimal debulking (both p<0.001), high tumor grade (p=0.025), serous histology
      (p=0.003) and high serum (>media) CA 125 (p=0.009). In multivariate analysis,
      only FIGO stage was of independent predictive value. These findings indicate
      that, although high levels of oCF CA 125 were significantly associated with a
      poor survival of EOC patients, CA 125 in oCF was not of independent predictive
      value and might therefore not be useful as a prognostic biomarker for EOC.

PMID- 20043125
TI  - (-)-Epigallocatechin-3-gallate inhibits invasion and migration of salivary gland
      adenocarcinoma cells.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) has inhibitory effect on a variety of
      cancers by inducing apoptosis and cell cycle arrest or inhibiting angiogenesis
      and metastasis. EGCG has been found to induce apoptosis in salivary gland
      carcinoma cells, however, it is not known whether EGCG affects invasion and
      migration. Thus, this study was performed to clarify whether EGCG affects
      invasion and migration of salivary gland tumors. Matrigel invasion assay, wound
      scratch assay and migration assay using commercial kit were performed. beta1
      integrin expression and activation of its downstream molecules such as focal
      adhesion kinase (FAK), AKT and extracellular signal-regulated kinase (ERK) were
      examined by Western blot. Enzymatic activity of matrix metalloprotease (MMP)-2
      and MMP-9 was examined by gelatin zymography. EGCG inhibited effectively invasion
      and migration of SGT cells in a dose-dependent manner. EGCG also inhibited the
      activation of beta1 integrin-downstream molecules such as FAK, AKT and ERK as
      well as the expression of beta1 integrin itself. Moreover, MMP-2 and MMP-9
      expression and their enzymatic activity were reduced by EGCG in a dose-dependent
      manner. These results indicate that EGCG may effectively suppress salivary gland
      tumors by inhibiting metastasis through beta1 integrin-mediated signaling.

PMID- 20043126
TI  - Long-term feeding of a synthetic diet rich in disaccharides induces hepatic
      fibrosis in nonalcoholic fatty liver disease in Zucker rats.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease, and is
      commonly observed in patients with obesity or type 2 diabetes. The pathogenesis
      of hepatic fibrosis is clinically important to the outcome of NAFLD, however, is
      not well understood. Since dietary habits are often considered to be responsible
      for NAFLD, we used a synthetic diet rich in disaccharides (12.1% calorie sucrose
      and lactose), which can be considered for human consumption. We examined the long
      term (24 weeks) effect of this diet on the liver of Zucker (fa/fa) rats. The
      synthetic diet-fed Zucker (fa/fa) rats showed hepatic fibrosis during the
      development of NAFLD with no apparent infiltration of inflammatory cells. They
      showed significantly elevated hepatic mRNA levels of proinflammatory and
      profibrogenic cytokines. These findings suggest that excess long-term feeding of
      a diet similar to the synthetic diet used in our study leads to hepatic fibrosis
      during the development of NAFLD in patients with obesity or type 2 diabetes. Our
      results were different from NAFLD accompanied by infiltration of inflammatory
      cells. However, they also suggest that long-term feeding of this synthetic diet
      to Zucker (fa/fa) rats is useful for studying the hepatic fibrogenesis during the
      pathogenesis of NAFLD.

PMID- 20043127
TI  - Pancreatic acellular matrix supports islet survival and function in a synthetic
      tubular device: in vitro and in vivo studies.
AB  - Increasing pancreatic islet survival and function is a starting point for
      obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes.
      In this context, decellularized matrices, obtained after the removal of tissue
      cellular part, are known to support in vitro adhesion, growth, and function of
      several cell types. We demonstrate that a homologous acellular pancreatic matrix
      is a suitable scaffold for rat islet cultures maintaining their long-term
      viability and function. Islets adhered to the pancreatic matrix showed a constant
      glucose-induced insulin release during long-term in vitro incubation, while
      islets cultured without a matrix or on the liver matrix showed a progressive
      reduction. In order to obtain implantable devices, acellular matrix/islet
      cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol)
      (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an
      in vitro constant insulin release was detected. The devices were then implanted
      into diabetic rats where reduced insulin requirement was noted suggesting insulin
      secretory activity of islets contained in the device. Indeed, immunofluorescence
      confirmed the presence of insulin- and glucagon-producing cells into the
      explanted devices. These data show that PVA/PEG semi-permeable membrane can
      obtain devices that restore, at least in part, insulin secretion.

PMID- 20043128
TI  - Proteus mirabilis sp. intestinal microflora grow in a dextran sulfate sodium-rich
      environment.
AB  - The pathogenic mechanisms responsible for inflammatory bowel disease, especially
      ulcerative colitis (UC), are poorly understood. As an animal model, the oral
      administration of dextran sulfate sodium (DSS) induces colitis, which exhibits
      several clinical and histological features similar to UC. However, the pathogenic
      factors responsible for DSS-induced colitis and above all, the intestinal
      microflora in this colitis remain unclear. Therefore, we investigated the
      relationships between DSS and the intestinal microflora in this study. First, the
      depolymerization of DSS in mouse feces was analyzed using a pyridylamino-labeling
      (PA-DSS) and HPLC system. Next, a bacteriological study of the fecal contents
      using DSS-rich media and subsequently a classification using 16S rRNA were
      performed. Surprisingly, DSS was depolymerized in mouse feces under aerobic
      conditions, not under anaerobic conditions. Several kinds of microflora were
      suggested to be involved in this depolymerization. In particular, Proteus
      mirabilis can grow in DSS-rich media and has an ability to desulfonate and
      depolymerize DSS. Then, we produced chemically-modified Mr 2500 DSS from native
      Mr 5000 DSS. This depolymerized Mr 2500 DSS was administered orally to mice and
      the colitis was evaluated histologically. The cytotoxicity of Mr 2500 DSS on Caco
      2 cells was also investigated. Mr 2500 DSS induced weaker colitis in mice and
      weak cytotoxicity on Caco-2 cells as compared to Mr 5000 DSS. These findings give
      insight into the mechanisms responsible for DSS-induced colitis, especially with
      respect to the molecular mass of DSS.

PMID- 20043129
TI  - Bispecific anti-HER2 and CD16 single-chain antibody production prolongs the use
      of stem cell-like cell transplantation against HER2-overexpressing cancer.
AB  - Humanized antibodies vary and have certain effects, but they are expensive and
      require repeated administration. We developed cells which constantly express a
      humanized antibody, and we performed anticancer humanized antibody therapy
      involving cell transplantation. Genes with the same amino acid sequence as that
      of the variable region of trastuzumab (Herceptin) as the humanized anti-HER2
      monoclonal antibody were produced by overlap-PCR and were connected to the anti
      human CD16 antibody [anti-HER2+anti-CD16 single-chain antibody (anti-HER2+CD16
      scAb)]. For transplantation, stem cell-like cells that are immunologically
      tolerant and do not transform into cancer [mouse embryo fibroblast cell line
      C3H10T1/2 (10T1/2)] were used. The antibody was incorporated into 10T1/2
      (antibody-expressing cells) using the pMX-IRES-EGFP retroviral vector. Cell
      supernatants and human monocytes were exposed to the human breast cancer strain
      HTB131 expressing HER2, and the in vitro antibody-dependent cell-mediated
      cytotoxicity (ADCC) effects were evaluated. After the transplantation of antibody
      expressing and HTB131 cells into SCID mice, human monocytes were intermittently
      administered, and the in vivo ADCC effects were evaluated. We found that the ex
      vivo dead cell rate was 15.4% for Herceptin, 5.6% for anti-HER2+CD16 scAb, 1.5%
      for anti-CD16 scAb, and 2.1% for the control, demonstrating the antitumor effects
      of anti-HER2+CD16 scAb. In an antibody-expressing cell transplantation model, the
      inhibitory effects of this antibody on HTB131 cell establishment were observed.
      In conclusion, the establishment of breast cancer cells in the peritoneum was
      inhibited by the transplantation of antibody-expressing cells. Since this method
      requires cell transplantation only once, the drug cost may be reduced.

PMID- 20043130
TI  - Impact of combinatory growth factor application on rabbit Achilles tendon injury
      with operative versus conservative treatment: a pilot study.
AB  - Acute Achilles tendon (AT) rupture is a common injury with a comparatively high
      complication rate. Presently, surgical treatments compete with nonoperative
      treatment modalities. The aim of this study was to elucidate the possible
      beneficial effects of short-term combinatory application of growth factors on
      tendon healing during operative or conservative treatment. In this controlled
      laboratory study, the left ATs of 40 adult New Zealand White rabbits were
      transected and either sutured or treated conservatively. Half of the animals from
      each treatment modality group repetitively received a mixture of VEGF165, bFGF,
      and rPDGF which was administered peritendineally. The left legs were immobilized
      with external fixateurs for 6 weeks. The ATs were harvested 3 months after
      intervention. Tensile strength tests revealed no significant differences between
      operative and conservative treatments. Compared to the normal right ATs, 60% of
      the average breaking strength was reached 3 months after surgery. Growth factor
      application did not result in significant improvements. Only a tendency towards
      higher blood vessel densities was noted in the groups treated with the factors.
      Collagen type I/III ratios also displayed no significant differences. This study
      indicates that there is no difference in the biomechanical outcome of
      conservative versus operative AT rupture treatment and only a marginal impact of
      short-term combinatory growth and angiogenesis factor application.

PMID- 20043131
TI  - Sema4A induces cell morphological changes through B-type plexin-mediated
      signaling.
AB  - Semaphorins are a family of secreted and membrane-bound proteins known as axonal
      pathfinders. Sema4A, a member of class 4 semaphorins, induces growth cone
      collapse of hippocampal neurons. The binding of Sema4A to growth cones indicates
      the presence of receptors transmitting signals through the intracellular
      effectors to induce growth cone collapse in hippocampal neurons. Transfection
      experiments of the candidate receptor genes into COS-7 cells demonstrated that
      Sema4A binds to axonal guidance receptors Plexin-B1, -B2 and -B3. To identify the
      functional Sema4A receptor and the signal transduction machinery, COS-7 cell
      contraction assay was performed, in which intracellular signal transmission
      induced by Sema4A triggered cell contraction. Expression vectors encoding plexins
      and Rnd1, a Rho family GTPase, were transfected into COS-7 cells, and a
      proportion of contracted cells among the transfectants was determined after
      incubation with Sema4A. The results demonstrated that the combination of Rnd1 and
      Plexin-B1, -B2 or -B3 induced significant cell contraction, indicating that B
      type plexins transmit an intracellular signal of Sema4A through Rnd1. To further
      study the mechanism of B-type plexin-mediated signaling in Sema4A-induced growth
      cone collapse, mouse hippocampal neurons transfected with a control or expression
      plasmid encoding a constitutively active mutant of R-Ras (R-RasQL) were
      stimulated with Sema4A, followed by the assessment of growth cone collapse.
      Expression of R-RasQL significantly blocked Sema4A-induced growth cone collapse
      in the hippocampal neurons compared with the control plasmid. Sema4A thus induces
      growth cone collapse through the down-regulation of R-Ras activity in mouse
      hippocampal neurons.

PMID- 20043132
TI  - Tanshinone IIA induces apoptosis in human lung cancer A549 cells through the
      induction of reactive oxygen species and decreasing the mitochondrial membrane
      potential.
AB  - Tanshinone IIA (Tan-IIA) is extracted from Danshen and known to inhibit
      proliferation and induce apoptosis in many cancer cells. We aimed to elucidate
      its anticancer activity and molecular mechanism in human lung cancer A549 cells.
      The cytotoxicity of Tan-IIA in A549 cells were measured by the MTT assay. The
      effects of Tan-IIA on the cell cycle, mitochondrial membrane potential (MMP),
      calcium and reactive oxygen species (ROS) released in A549 cells were detected by
      flow cytometry. The protein expressions of p53, Bax, Bcl-2 and beta-actin in A549
      cells were tested by Western blotting. The proliferative rates of A549 cells were
      obviously inhibited by Tan-IIA in a dose- and time-dependent manner. The results
      of FACS showed that the sub-G1 phase was increased when A549 cells were cultured
      with various concentrations of Tan-IIA (control, 2.5, 5 and 10 microg/ml) for 48
      h. Tan-IIA induced the production of ROS, Ca+2 and decreased MMP. The outcome of
      Western blotting showed that protein expressions of p53 and bax were increased,
      but proto-oncogene bcl-2 was notably decreased, after culturing with Tan-IIA (5
      microg/ml) for 6, 12 and 24 h. Tan-IIA inhibited the proliferation of non-small
      cell lung cancer A549 cells, possibly by decreasing the MMP and inducing
      apoptosis due to the induction of a higher ratio of Bax/Bcl-2.

PMID- 20043133
TI  - Proteomics approach to study the mechanism of action of grape seed
      proanthocyanidin extracts on arterial remodeling in diabetic rats.
AB  - Arterial remodeling is the change in structural properties of vessel in diabetes
      mellitus and contributes to the development of vascular complications. To prevent
      this development and to improve diabetic vascular complications, effective
      therapies directed toward the key molecular target are required. Grape seed
      proanthocyanidin extracts (GSPE) have been reported to be effective in treating
      arteriosclerosis, while little is known about the functional protein changes. We
      used streptozocin to induce diabetic rats. GSPE (250 mg/kg body weight/day) were
      administrated to diabetic rats for 24 weeks. Consequently, 2-D difference gel
      electrophoresis and mass spectrometry were used to investigate aortic protein
      profiles among the control, untreated and GSPE- treated diabetic rats. The
      expression of 23 proteins was found either up-regulated or down-regulated in the
      aorta of untreated diabetic rats. Only the expression of 15 proteins was found
      either down-regulated or up-regulated in the aorta of GSPE- treated diabetic
      rats. Our findings might help to better understand the mechanism of diabetic
      macrovascular complications and provide novel targets for evaluating the effects
      of GSPE therapy.

PMID- 20043134
TI  - Visualization of the melanosome transfer-inhibition in a mouse epidermal cell co
      culture model.
AB  - Transfer of melanin-containing melanosomes from melanocytes to neighboring
      keratinocytes results in skin pigmentation. To provide a more practical method of
      visualizing melanosomes in melanocytes as well as in keratinocytes, we attempted
      to use murine cell lines instead of human primary cells. We generated various
      fluorescent fusion proteins of tyrosinase, a melanin synthesis enzyme located in
      the melanosome, by using green fluorescent protein and red fluorescent protein.
      The intracellular localization of tyrosinase was then examined by fluorescence
      and confocal microscopy. Co-culture of murine melanocytes and keratinocytes was
      optimized and melanosome transfer was either stimulated with alphaMSH or
      partially inhibited by niacinamide. To the best of our knowledge, this is the
      first study showing that a murine co-culture model, in addition to human primary
      cell co-culture, can be a good tool for depigmenting agent screening by
      monitoring melanosome transfer.

PMID- 20043135
TI  - Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by
      suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells.
AB  - Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix
      (ECM), plays an important role in breast cancer cell invasion. NF-kappaB and AP-1
      are known to induce MMP-9 expression. We investigated whether cordycepin, an NF
      kappaB or AP-1 inhibitor, can modulate MMP-9 expression and cell invasion in MCF
      7 cells. Toxicity of cordycepin was determined by 3-(4,5-dimethyl-thiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay. MMP-9 expression was determined by
      real-time PCR, Zymography, and Western blot analysis. AP-1 activation was assayed
      by electrophoretic mobility shift assay (EMSA). MAPK signaling was evaluated by
      Western blotting with specific p-ERK, and ERK, p-p38, p38, p-JNK, JNK antibodies.
      Cordycepin suppressed AP-1 activation, but not NF-kappaB activation in 12-O
      tetradecanoylpho-bol-13-acetate (TPA)-treated MCF-7 cells. Cordycepin inhibits
      TPA-induced MMP-9 expression and cell invasion by suppressing AP-1 activation.
      Also, cordycepin suppressed the MAPK signaling pathway. Cordycepin is a potent
      inhibitor of TPA-induced MMP-9 expression and blocks strongly the ability of AP-1
      activation via MAPK signaling pathway in MCF-7 cells.

PMID- 20043136
TI  - A PET study examining pharmacokinetics and dopamine transporter occupancy of two
      long-acting formulations of methylphenidate in adults.
AB  - The delivery systems of two long-acting formulations of methylphenidate (MPH)
      were designed for different durations. Diffucaps bead-delivery system (DBDS)-MPH
      was designed to last 8 h and osmotically controlled-release oral delivery system
      (OROS)-MPH was designed to last 12 h. While the plasma pharmacokinetics and
      timing of efficacy have been studied, the corresponding central nervous system
      dopamine transporter (DAT) occupancies are unknown. In this study, 21 healthy
      volunteers underwent PET imaging with 11C Altropane before and after
      administration of oral doses of DBDS-MPH and OROS-MPH. Each subject received 40
      mg DBDS-MPH and 36 mg OROS-MPH on different days. PET imaging occurred at 10 h
      after dosing. Each subject was injected with 5 mCi of 11C Altropane and serial
      images of the brain were acquired over 60 min with a Siemens HR+ PET camera.
      Binding potentials (BP, k3/k4) were calculated from time-activity curves using
      the simplified reference region method with cerebellum as reference. Transporter
      occupancy was calculated by standard methods. At 10 h, plasma d-MPH levels were
      lower (3.8+/-1.2 vs. 5.2+/-2.0) and brain DAT occupancy was lower (34.8+/-12.9
      vs. 44.3+/-11.8) for DBDS-MPH than OROS-MPH. Across the range of values, for each
      unit of change in plasma d-MPH level there was a larger change in DAT occupancy
      with the DBDS-MPH formulation than with the OROS-MPH formulation. As predicted
      from previous pharmacokinetic and efficacy data, the average plasma level and DAT
      occupancy of 36 mg OROS-MPH was >40 mg DBDS-MPH at 10 h. Moreover, a relatively
      small difference in plasma levels (1.4 ng/ml at 10 h) was associated with a more
      impressive difference in DAT occupancy ( approximately 10% at 10 h).

PMID- 20043137
TI  - Degradation and destabilization of abnormal prion protein using alkaline
      detergents and proteases.
AB  - There is a limited number of reports regarding detergents and proteases
      inactivating, degrading, or destabilizing abnormal prion protein (PrPSc). In the
      present study, the effect of alkaline detergents and proteases on the breakdown
      of PrPSc in the absence of proteinase K (PK) (degradation) and the presence of PK
      (destabilization) was investigated. PrPSc from brain homogenate of terminally
      diseased mice infected with the Chandler strain of scrapie was used as a
      substrate. A surfactant-free alkaline detergent (pH 11.9, 1% aqueous solution)
      with potassium hydroxide as the main ingredient and an alkaline detergent (pH
      11.9, 1% aqueous solution) containing about 1% surfactant as well as two
      commercially available alkaline proteases had a destabilizing effect on PrPSc.
      All these detergents and proteases showed degradative effects on PrPSc under
      appropriate conditions. These results demonstrate the usefulness of alkaline
      detergents and proteases for the degradation or destabilization of PrPSc.

PMID- 20043138
TI  - Influence of LOX/COX inhibitors on cell differentiation induced by all-trans
      retinoic acid in neuroblastoma cell lines.
AB  - We investigated the possible modulation by LOX/ COX inhibitors of all-trans
      retinoic acid (ATRA)-induced cell differentiation in two established
      neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Caffeic acid, as an inhibitor
      of 5-lipoxygenase, and celecoxib, as an inhibitor of cyclooxygenase-2, were
      chosen for this study. The effects of the combined treatment with ATRA and
      LOX/COX inhibitors on neuroblastoma cells were studied using cell morphology
      assessment, detection of differentiation markers by immunoblotting, measurement
      of proliferation activity, and cell cycle analysis and apoptosis detection by
      flow cytometry. The results clearly demonstrated the potential of caffeic acid to
      enhance ATRA-induced cell differentiation, especially in the SK-N-BE(2) cell
      line, whereas application of celecoxib alone or with ATRA led predominantly to
      cytotoxic effects in both cell lines. Moreover, the higher sensitivity of the SK
      N-BE(2) cell line to combined treatment with ATRA and LOX/COX inhibitors suggests
      that cancer stem cells are a main target for this therapeutic approach.
      Nevertheless, further detailed study of the phenomenon of enhanced cell
      differentiation by expression profiling is needed.

PMID- 20043139
TI  - Association of genetic variants with ischemic stroke in Japanese individuals with
      or without metabolic syndrome.
AB  - Although metabolic syndrome has been recognized as a risk factor for ischemic
      stroke, genetic factors associated with ischemic stroke in individuals with
      metabolic syndrome remain unknown. We examined an association of genetic variants
      with ischemic stroke among individuals with or without metabolic syndrome. The
      study population comprised 4,387 unrelated Japanese individuals, including 1,884
      individuals with metabolic syndrome (240 subjects with ischemic stroke and 1,644
      controls) and 2,503 individuals without metabolic syndrome (280 subjects with
      ischemic stroke and 2,223 controls). The 150 polymorphisms examined in the
      present study were selected by genome-wide association studies of ischemic stroke
      and myocardial infarction with the use of the GeneChip Human Mapping 500K Array
      Set (Affymetrix). The initial chi-square test revealed that the Cright curved
      arrow T polymorphism (rs9925481) of CLEC16A and the Aright curved arrow G
      polymorphism (rs4923918) of SPTBN5 were significantly (P<0.005) associated with
      ischemic stroke among individuals with metabolic syndrome. No polymorphism was
      significantly associated with ischemic stroke among individuals without metabolic
      syndrome. Multivariable logistic regression analysis with adjustment for
      covariates and a stepwise forward selection procedure revealed that the Aright
      curved arrow G polymorphism (rs4923918) of SPTBN5 was significantly (P<0.005),
      and the Cright curved arrow T polymorphism (rs9925481) of CLEC16A was almost
      significantly, associated with ischemic stroke in individuals with metabolic
      syndrome. Genetic variants that confer susceptibility to ischemic stroke may
      differ among individuals with or without metabolic syndrome. Stratification of
      subjects according to the presence or absence of metabolic syndrome may thus be
      important for personalized prevention of ischemic stroke based on genetic
      information.

PMID- 20043140
TI  - Partially purified Asiasari radix inhibits melanogenesis through extracellular
      signal-regulated kinase signaling in B16F10 cells.
AB  - The active fraction of the extract of Asiasari radix, the 60% methanol
      chromatographic fraction from the ethyl acetate layer (PPAR), was used to
      investigate the melanogenesis signal pathway in B16F10 melanoma cells. PPAR led
      to significantly decreased melanin synthesis and tyrosinase activity in a dose
      dependent manner. PPAR also reduced the expression of melanogenesis-related
      proteins including microphthalmia-associated transcription factor (MITF),
      tyrosinase, and tyrosinase-related protein (TRP)s while down-regulating the
      expression of mRNA of MITF and tyrosinase. Melanogenesis-regulating signals, such
      as mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase
      (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and p38 mitogen-activated protein
      kinase (MAPK) were evaluated, and ERK was activated by PPAR. The selective
      inhibitor of MEK/ERK, PD98059, abrogated all suppressive activities of PPAR on
      melanin biosynthesis, tyrosinase activation and expression of melanogenesis
      related proteins. These results suggest that ERK activation by PPAR contributes
      to reduced melanin synthesis via ERK signal pathway-mediated suppression of MITF
      and its downstream signal pathway.

PMID- 20043141
TI  - Anti-carcinogenic effect of a new analogue 4'-chloroflavanone from flavanone in
      human breast cancer cells.
AB  - We investigated the antiproliferative effects of synthetic flavanone derivatives
      using an MTT assay in MCF-7 and MDA-MB-453 cells. When cells were treated with
      synthetic flavanone derivatives in concentrations ranging from 1 to 200 microM
      for 48 h, cell growth decreased at concentrations >50 microM. 4'-Chloroflavanone
      is more potent than flavanone among the synthetic flavanone derivatives. Exposure
      to 4'-chloroflavanone at 50 microM for 48 h caused cell cycle arrest in both MCF
      7 and MDA-MB-453 cells. In addition, when 4'-chloroflavanone caused G1/S phase
      arrest, a decrease in CDK4 and cyclin D, together with an increase in p21Cip1,
      was observed in the cells. The p21Cip1 is a downstream target of p53 that may be
      affected by the activation of p53 by 4'-chloroflavanone. These results indicate
      that activation of p53 played some role in 4'-chloroflavanone-induced cell cycle
      arrest of human breast cancer cells. 4'-Chloroflavanone increased cytochrome c
      expression and decreased the expression of caspase-3, but did not change the
      expression of Bcl-2 and Bax. Activation of cytochrome c and its downstream
      target, caspase-3, is suggested to be an important inducer of the apoptosis
      process by 4'-chloroflavanone. 4'-Chloroflavanone inhibits cell proliferation
      through G1/S phase disruption and may induce apoptosis. Based on our findings, we
      propose that 4'-chloro-flavanone is useful as an anticancer drug.

PMID- 20043142
TI  - Integrative genomic analyses on interferon-lambdas and their roles in cancer
      prediction.
AB  - Interferon (IFN)-lambdas, including IFN-lambda1, IFN-lambda2, and IFN-lambda3,
      are a newly described group of cytokines distantly related to the type I IFNs and
      IL-10 family members. Besides the antiviral activity, IFN-lambdas were reported
      to inhibit various tumor growths in vitro and in vivo. Herein, we identified IFN
      lambda genes from the genome sequences of the human, chimpanzee, macaque,
      orangutan, mouse, rat and dog, and found that the locations and copy of a
      specific IFN-lambda varied in different genomes, not just the copy of IFN
      lambdas. We found human IFN-lambdas were expressed in fetal retina, fetal brain
      and T cells by ESTs search. Moreover, IFN-lambdas were also found to express in
      bladder cancer, blood cancer, breast cancer, glioma, head and neck cancer and
      lung cancer tissues. Three tumor-related transcriptional factors (steroidogenic
      factor-1, Wilms tumor 1 and P53) binding sites were identified within the 1.0-kb
      regions upstream of the transcriptional start site of human IFN-lambdas. Meta
      analysis of the prognostic value of IFN-lambda genes in various cancers showed
      that the expression of IFN-lambdas are indeed related to the cancer prognosis in
      certain types of cancer. It can be predicted that IFN-lambdas take part in the
      cancer development by the regulation of expression of IFN-lambdas related to the
      SF-1, P53 and WT-1.

PMID- 20043143
TI  - Biguanides and thiazolidinediones inhibit stimulated lipolysis in human
      adipocytes through activation of AMP-activated protein kinase.
AB  - AIMS/HYPOTHESIS: In rodent adipocytes, activated AMP-activated protein kinase
      reduces the lipolytic rate. As the hypoglycaemic drugs metformin and
      thiazolidinediones activate this enzyme in rodents, we tested the hypothesis that
      in addition to their known actions they could have an anti-lipolytic effect in
      human adipocytes. METHODS: Adipose tissue was obtained from individuals
      undergoing plastic surgery. Adipocytes were isolated and incubated with lipolytic
      agents (isoprenaline, atrial natriuretic peptide) and biguanides or
      thiazolidinediones. Lipolysis was quantified by the glycerol released in the
      medium. AMP-activated protein kinase activity and phosphorylation state were
      determined using standard procedures. RESULTS: In human adipocytes, isoprenaline
      and atrial natriuretic peptide stimulated the lipolytic rate three- to fourfold.
      Biguanides and thiazolidinediones activated AMP-activated protein kinase and
      inhibited lipolysis by 30-40%, at least in part by inhibiting hormone-sensitive
      lipase translocation to the lipid droplet. Inhibition of AMP-activated protein
      kinase by compound C precluded this inhibitory effect on lipolysis. Stimulation
      of lipolysis also induced an activation of AMP-activated protein kinase
      concomitant with a drop in ATP concentration. CONCLUSIONS/INTERPRETATION: We show
      for the first time in human adipocytes that biguanides and thiazolidinediones
      activate AMP-activated protein kinase, thus counteracting lipolysis induced by
      lipolytic agents. In addition, beta-agonist- or ANP-stimulated lipolysis
      increases AMP-activated protein kinase activity. This is because of an increase
      in the AMP/ATP ratio, linked to activation of some of the released fatty acids
      into acyl-CoA. AMP-activated protein kinase activation could represent a
      physiological means of avoiding a deleterious drain of energy during lipolysis
      but could be used to restrain pharmacological release of fatty acids.

PMID- 20043144
TI  - Life-course weight characteristics and the risk of gestational diabetes.
AB  - AIMS/HYPOTHESIS: We prospectively determined the risk of gestational diabetes
      mellitus in association with life-course weight characteristics and adult
      abdominal adiposity. METHODS: We investigated the joint and independent impact of
      birthweight, childhood size by somatotypes, adolescent and adult BMI, and
      abdominal adiposity on gestational diabetes mellitus risk among the 21,647 women
      in the Nurses' Health Study II who reported a singleton pregnancy between 1989
      and 2001. A total of 1,386 incident cases of gestational diabetes mellitus were
      reported. Relative risk was estimated by pooled logistic regression adjusting for
      age, prematurity, race, smoking status, parental history of diabetes, age of
      first birth, parity and physical activity. RESULTS: Birthweight was inversely
      associated with gestational diabetes mellitus risk (p = 0.02 for trend).
      Childhood somatotypes at ages 5 and 10 years were not associated with risk. U
      shaped associations were found for BMI at age 18 years and somatotype at age 20
      years. Weight gain between adolescence and adulthood, pre-gravid BMI and
      abdominal adiposity were positively associated with risk (p < 0.01 for all
      trends). Multivariate adjusted RRs for gestational diabetes from lowest to
      highest quintile of WHR were 1.00, 1.50, 1.51, 2.03, 2.12 (p = 0.0003 for trend).
      Lower birthweight (<7 lb) without adulthood overweight (BMI > 25 kg/m(2)) was
      associated with a 20% increased risk (95% CI 1.02-1.41). However, adulthood
      overweight alone was related to a 2.36 times greater risk (95% CI 2.12-3.77).
      CONCLUSIONS/INTERPRETATION: Although lower birthweight is an independent risk
      factor for gestational diabetes mellitus, weight gain since early adulthood, and
      overall and central obesity in adulthood were more strongly associated with
      elevated risk of the condition independently of other known risk factors.

PMID- 20043145
TI  - Improvements in glucose homeostasis in response to regular exercise are
      influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study.
AB  - AIMS/HYPOTHESIS: Exercise training improves glucose homeostasis, but large inter
      individual differences are reported, suggesting a role of genetic factors. We
      investigated whether variants either confirmed or newly identified as diabetes
      susceptibility variants through genome-wide association studies (GWAS) modulate
      changes in phenotypes derived from an IVGTT in response to an endurance training
      programme. METHODS: We analysed eight polymorphisms in seven type 2 diabetes
      genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX
      rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2
      rs7903146) in a maximum of 481 sedentary, non-diabetic white individuals, who
      participated in a 20-week endurance training programme. Associations were tested
      between the variants and changes in IVGTT-derived phenotypes. RESULTS: The only
      evidence of association with training response was found with PPARG rs1801282
      (Pro12Ala). We observed that Ala carriers experienced greater increase in overall
      glucose tolerance (Deltaglucose disappearance index Ala/Ala 0.22 +/- 0.22,
      Pro/Ala 0.14 +/- 0.06, Pro/Pro 0.004 +/- 0.03; p = 0.0008), glucose effectiveness
      (Ala/Ala 0.28 +/- 0.41, Pro/Ala 0.44 +/- 0.14, Pro/Pro 0.09 +/- 0.06; p = 0.004),
      acute insulin response to glucose (Ala/Ala 64.21 +/- 37.73, Pro/Ala -11.92 +/-
      40.30, Pro/Pro -46.30 +/- 14.70; p = 0.03) and disposition index (Ala/Ala 551.8
      +/- 448.5, Pro/Ala 534.6 +/- 218.3, Pro/Pro -7.44 +/- 88.18; p = 0.003).
      CONCLUSIONS/INTERPRETATION: Compared with Pro/Pro individuals, PPARG Ala carriers
      experienced greater improvements in glucose and insulin metabolism in response to
      regular endurance training. However, we did not find evidence of association
      between type 2 diabetes susceptibility variants recently identified through GWAS
      and glucose homeostasis response to exercise. Our results extend those of
      previous studies showing that Ala carriers appear to be more responsive to
      beneficial health effects of lifestyle interventions.

PMID- 20043146
TI  - The association between substance misuse and first-episode psychosis in a defined
      UK geographical area during the 1990s.
AB  - OBJECTIVE: The aim of this study was to examine the prevalence of all substance
      use disorders (SUD) and cannabis-specific SUDs reported in two first-episode
      epidemiological studies, conducted in the same catchment area, 5 years apart.
      METHODS: The prevalence of schizophrenia in Nottingham and Aetiology and
      Ethnicity of Schizophrenia and Other Psychoses studies included all people with a
      first-episode of psychosis between 1992 and 1994 and 1997 and 1999, respectively.
      Those individuals with a comorbid diagnosis of a SUD (ICD-10 harmful use or
      dependence) were identified. RESULTS: An upward (but not statistically
      significant) trend in all SUDs was found for the first-episode study population
      as a whole, between the two cohorts (11.9-18.2%). When analysed by age, a
      significant increase in cannabis-specific SUDs was observed for all first-episode
      cases aged 16-29 between cohorts (3.2-10.6%). When analysed by age and gender, a
      significant increase in all SUDs was apparent for female first-episode patients
      aged 16-29 between cohorts (6.1-24.2%), this same increase was not seen in male
      patients. CONCLUSIONS: Illegal drug misuse is common in patients with a first
      episode of psychosis. However, most concerning is that when both age and gender
      are considered, females with a first-episode of psychosis aged 16-29 show a
      highly significant rise in the prevalence of all SUDs over the 1990s. More recent
      drug use data from England and Wales shows that the prevalence of drug use in the
      21st century is declining; further epidemiological studies are required to
      determine whether this is also the case in young female first-episode psychosis
      populations.

PMID- 20043147
TI  - Evaluation of combined toxicity of phenols and lead to Photobacterium phosphoreum
      and quantitative structure-activity relationships.
AB  - The combined toxicity of lead (Pb) and nine phenols were measured. The result
      indicated that the combined toxicity is not only dependent on the Pb
      concentrations but also on the positions of substituted groups of phenols.
      Quantitative structure-activity relationship equations were built from the
      combined toxicity and physico-chemical descriptors of phenols in the different Pb
      concentrations. The combined toxicity was related to water solubility and the
      third order molecular connectivity index ((3)X) in low Pb concentration, to
      solute excess molar refractivity (E) and ionization constant (pKa) in medium Pb
      concentration and to dipolarity/polarizability (S) in high Pb concentration.

PMID- 20043148
TI  - Manipulation of a fragile object.
AB  - We investigated strategies of adjustments in kinetic and kinematic patterns, and
      in multi-digit synergies during quick vertical transport of an instrumented
      handle that collapsed when the grasping force exceeded a certain magnitude
      (quantified with a fragility index). The collapse threshold of the object was set
      using a novel electromagnetic device. Moving a fragile object is viewed as a task
      with two constraints on the grip force defined by the slipping and crushing
      thresholds. When moving more fragile objects, subjects decreased object peak
      acceleration, increased movement time, showed a drop in the safety margin (SM)
      (extra force over the slipping threshold), and showed a tendency toward violating
      the minimum-jerk criterion. Linear regression analysis of grip force against load
      force has shown tight coupling between the two with a decline in the coefficient
      of determination with increased fragility index. The SM was lower in bimanual
      tasks, compared to unimanual tasks, for both fragile and non-fragile objects. Two
      novel indices have been introduced and studied, the SM due to fragility and the
      drop-crush index. Both indices showed a decrease with increased object fragility.
      Changes in the drop-crush index showed that the subjects would rather crush the
      fragile objects as opposed to dropping them, possibly reflecting the particular
      experimental procedure. We did not find differences between the performance
      indices of the dominant and non-dominant hand thus failing to support the
      recently formulated dominance hypothesis. The synergies stabilizing grip force
      were quantified at two levels of an assumed two-level control hierarchy using co
      variation indices between elemental variables across trials. There were strong
      synergies at the upper level of the hierarchy (the task is shared between the
      opposing groups of digits) that weakened with an increase in object fragility. At
      the lower level (action of an effector is shared among the four fingers), higher
      fragility led to higher synergy indices. Analysis of force variance showed that
      an increase in object fragility was accompanied by exploring a smaller range of
      equivalent combinations of elemental variables. The additional constraint imposed
      by high fragility facilitated synergies at the lower level of the hierarchy,
      while there was evidence for a trade-off between synergies at the two levels.

PMID- 20043150
TI  - Characterization of beta-glucosidase from a strain of Penicillium purpurogenum
      KJS506.
AB  - A novel beta-glucosidase (BGL)-producing strain was isolated and identified as
      Penicillium purpurogenum KJS506 based on its morphology and internal transcribed
      spacer (ITS) rDNA gene sequence. When rice straw and corn steep powder were used
      as carbon and nitrogen sources, respectively, the maximal BGL activity of 12.3 U
      ml(-1), one of the highest levels among BGL-producing microorganisms was
      observed. The optimum temperature and pH for BGL production were 32 degrees C and
      4, respectively. An extracellular BGL was purified to homogeneity by sequential
      chromatography of P. purpurogenum culture supernatants, and the purified BGL
      showed higher activity (V (max) = 934 U mg protein(-1)) than most BGLs from other
      sources. The complete ORF of bgl3 was cloned from P. purpurogenum by a modified
      thermal asymmetric interlaced polymerase chain reaction. The bgl3 gene consists
      of a 2,571-bp ORF and encodes a putative protein containing 856 amino acids with
      a calculated molecular mass of 89,624 Da. The putative gene product was
      identified as a member of glycoside hydrolase family 3. The present results
      should contribute to improved industrial production of BGL by P. purpurogenum
      KJS506.

PMID- 20043149
TI  - O-GlcNAc modification of proteins affects volume regulation in Jurkat cells.
AB  - An increasing amount of recent research has demonstrated that the hexosamine
      biosynthesis pathway (HBP) plays a significant role in the modulation of
      intracellular signaling transduction pathways, and affects cellular processes via
      modification of protein by O-linked beta-N-acetylglucosamine (O-GlcNAc). Besides
      the many known and postulated effects of protein O-GlcNAc modifications, there is
      little available data on the role of O-GlcNAc in cellular volume regulation. Our
      objective was to test the effect of increased O-GlcNAc levels on hypotonia
      induced volume changes in Jurkat cells. We pretreated Jurkat cells for 1 h with
      glucosamine (GlcN), PUGNAc (O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N
      phenylcarbamate) an inhibitor of O-GlcNAcase, or a high level of glucose to
      induce elevated levels of O-GlcNAc. We found that the response of Jurkat cells to
      hypotonic stress was significantly altered. The hypotonia induced cell-swelling
      was augmented in both GlcN and PUGNAc-treated cells and, to a lesser extent, in
      high glucose concentration-treated cells. Evaluated by NMR measurements, GlcN and
      PUGNAc treatment also significantly reduced intracellular water diffusion. Taken
      together, increased cell swelling and reduced water diffusion caused by elevated
      O-GlcNAc show notable analogy to the regulatory volume changes seen by magnetic
      resonance methods in nervous and other tissues in different pathological states.
      In conclusion, we demonstrate for the first time that protein O-GlcNAc could
      modulate cell volume regulation.

PMID- 20043152
TI  - Treatment of axillary hyperhidrosis/bromidrosis using VASER ultrasound.

PMID- 20043151
TI  - Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial
      cultures from sediments.
AB  - Nonylphenol (NP) is an estrogenic pollutant which is widely present in the
      aquatic environment. Biodegradation of NP can reduce the toxicological risk. In
      this study, aerobic biodegradation of NP in river sediment was investigated. The
      sediment used for the microcosm experiments was aged polluted with NP. The
      biodegradation of NP in the sediment occurred within 8 days with a lag phase of 2
      days at 30 degrees C. During the biodegradation, nitro-nonylphenol metabolites
      were formed, which were further degraded to unknown compounds. The attached nitro
      group originated from the ammonium in the medium. Five subsequent transfers were
      performed from original sediment and yielded a final stable population. In this
      NP-degrading culture, the microorganisms possibly involved in the
      biotransformation of NP to nitro-nonylphenol were related to ammonium-oxidizing
      bacteria. Besides the degradation of NP via nitro-nonylphenol, bacteria related
      to phenol-degrading species, which degrade phenol via ring cleavage, are
      abundantly present.

PMID- 20043153
TI  - Capsular flaps for the management of malpositioned implants after augmentation
      mammoplasty.
AB  - Among the reasons for reoperation after augmentation mammaplasty is the
      malpositioned implant, especially a lowered inframammary fold or symmastia, which
      is difficult to repair. The peri-implant capsule, a physiologic response to a
      foreign body, is naturally formed and suitable for use as a flap because of its
      high vascularity. In addition, it is sufficiently tough for suspension of the
      implant. The authors introduce the idea that the capsular flap is very useful for
      the correction of symmastia or a lowered inframammary fold. In such situations,
      the capsular flaps are used to prevent migration of the implant after raising of
      the inframammary fold or defining of the midline with capsulorrhaphy. This
      technique successfully corrected the malpositioned implants in this study, and
      all the patients were satisfied. There was no recurrence of a lowered
      inframammary fold or symmastia. These findings suggest that the capsular flap
      should be considered a safe and effective option for the management of
      malpositioned implants.

PMID- 20043154
TI  - Techniques for labia minora reduction: an algorithmic approach.
AB  - BACKGROUND: Aesthetic reduction of the labia minora has gained popularity, and a
      number of different techniques have been described. Each procedure has its own
      set of advantages and disadvantages. However, no algorithm has been defined for
      pairing the degree of deformity with the optimal surgical procedure. METHODS:
      Patients were stratified into one of four groups based on labial size. The
      surgeon chose one of three reduction techniques based on the degree of labial
      hypertrophy and the patient's aesthetic preferences for labial edge color and
      contour. Three reduction techniques were used including the edge excision
      technique, the inferior wedge resection technique, and deepithelialization
      reduction labioplasty. The success of aesthetic reduction was evaluated, as was
      symptomatic relief. RESULTS: The 12 procedures performed included five
      deepithelialization techniques, four edge excision techniques, and three inferior
      wedge resection techniques. As reported, 92% of the patients were "very
      satisfied" with their aesthetic and functional results. The complications were
      minimal, with three patients experiencing minor wound healing difficulties that
      resolved spontaneously. One patient who underwent the edge excision technique was
      "not satisfied" and complained of overreduction. CONCLUSION: The authors found
      all three techniques for labia minora reduction to be useful in different
      clinical situations. A novel algorithm is described for matching the optimal
      surgical technique for each patient based on her degree of hypertrophy and
      aesthetic goals.

PMID- 20043155
TI  - The use of quilting suture in abdominoplasty does not require aspiratory drainage
      for prevention of seroma.
AB  - BACKGROUND: The formation of seromas after abdominoplasty is a highly prevalent
      complication that disturbs both the patient and the surgeon. Aspiratory drainage
      and adhesion sutures (Baroudi suture) are widely used to prevent this
      complication. This study evaluated the effectiveness of drains in preventing
      seromas. METHODS: This retrospective study investigated women submitted to
      classic abdominoplasty with adhesion sutures. The women were divided into two
      groups. Group 1 comprised 28 individuals who received no drains, and group 2
      consisted of 32 patients that had drains placed. Clinical evaluation of the
      patients was performed 7 days, 14 days, 1 month, 2 months, 4 months, and 6 months
      postoperatively. Statistical analysis was accomplished via Fisher's exact test.
      RESULTS: Group 1 had one case of seroma (3.5%), clinically detected between the
      first and second postoperative months, whereas group 2 had one case (3.12%)
      detected 14 days postoperatively. Fisher's test showed a P value of 1.000 (not
      statistically significant), for a 95% confidence interval of 0.05 to 14.08 and an
      odds ratio of 0.8387. Clinical evaluation showed no statistical difference in the
      incidence of seromas after abdominoplasty with adhesion sutures between the
      patients who received drains and those who did not. CONCLUSION: The use of
      adhesion sutures is an effective measure for preventing seromas with no need for
      additional surgical measures.

PMID- 20043157
TI  - A new technique for gluteal lifting using deepithelialized dermal flaps.
AB  - BACKGROUND: Gluteal ptosis may result from sagging of redundant skin and fat
      below the infragluteal fold. The correction of gluteal ptosis and the definition
      of gluteal prominence can be obtained by several gluteal lifting techniques. We
      present a new technique to correct gluteal ptosis using deepithelialized dermal
      flaps. METHODS: Eight female patients (39 + or - 4 years old) with gluteal ptosis
      were included in the study. Six patients had been previously operated on
      elsewhere (liposuction, body lift). Gluteal lifting is performed using a crescent
      shaped deepithelialized flap. The cranial two-thirds of the flap is sutured to
      the gluteal fascia, thus creating the new gluteal curvature and the position of
      the new infragluteal fold. The lower third of the flap is then sutured back
      toward the two-thirds flap within the first suture line, resulting in a doubling
      of the deepithelialized area. RESULTS: The mean operating time was 100 + or - 20
      min (range = 75-110 min). There were no complications in the study group. An
      analysis of postoperative results revealed a very good aesthetic aspect in all
      patients. All patients showed an improved definition of the infragluteal fold,
      with a symmetric shape of the gluteal region. All patients judged the outcome as
      very good. CONCLUSION: The use of a deepithelialized double dermal flap is a safe
      and new way to obtain excellent results in rejuvenation of the gluteal region.
      Our technique allows for the creation of a stable and long-lasting infragluteal
      fold with an aesthetic buttock curvature and a defined border to the thigh
      region.

PMID- 20043158
TI  - Trapezoid excision upper blepharoplasty for Chinese women with severe laxity of
      pretarsal skin.

PMID- 20043156
TI  - Skin-reducing subcutaneous mastectomy using a dermal barrier flap and immediate
      breast reconstruction with an implant: a new surgical design for reconstruction
      of early-stage breast cancer.
AB  - BACKGROUND: The development of skin-sparing mastectomy techniques for early-stage
      breast cancer has opened a new era in reconstructive breast surgery. Because of
      improved early diagnoses, the demand for skin-sparing techniques continues to
      increase more than ever. METHODS: Between March 2006 and April 2008, skin
      reducing subcutaneous mastectomy (SRSM) using the dermal barrier flap technique
      and simultaneous breast reconstruction with silicone implants was performed for
      15 patients (a total of 26 breasts) who had either a diagnosis of early-stage
      breast cancer or indications for prophylactic mastectomy. Of the 15 patients, 11
      underwent bilateral reconstruction. The remaining four patients underwent
      unilateral reconstruction using SRSM with the dermal barrier flap technique.
      RESULTS: The average age of the patients who underwent SRSM with the dermal
      barrier flap was 45.7 years. All the patients were discharged from the hospital
      on postoperative day 1. The mean follow-up period was 12 months, and the recovery
      time was 35 days. Excellent aesthetic results and uneventful healing were
      obtained for 23 breasts. Partial nipple-areola necrosis occurred in two breasts.
      Total skin necrosis in the bilateral nipple-areola and central breast region
      occurred for one patient who underwent bilateral SRSM. Prosthesis exposure was
      not observed for any of these patients. CONCLUSIONS: The authors present their
      early results with SRSM using the dermal barrier flap and silicone implants for
      early-stage breast cancer. The dermal barrier flap became a reliable procedure by
      providing a decreased breast envelope, eliminating the risk of implant exposure,
      and forming a double layer of dermal tissue at the incision line.

PMID- 20043160
TI  - Simultaneous augmentation and periareolar mastopexy: selecting the correct
      implant.
AB  - BACKGROUND: Periareolar mastopexy is a well-described technique for cosmetic
      improvement of breasts classified as Regnault ptosis grades 1 and 2. However,
      this technique is used less frequently for cases of grade 3 ptosis. METHODS:
      Grades 2 and 3 ptosis were corrected for selected patients using a combination of
      augmentation with Style 410 shaped, form-stable, highly cohesive, silicone gel
      implants and periareolar mastopexy. RESULTS: In this study, 17 patients were
      treated. The Style 410 implants used included four different devices: FX (full
      height, extra-full projection, n = 4), MX (medium height, extra-full projection,
      n = 1), MF (medium height, full projection, n = 8), and FF (full height, full
      projection, n = 4). No complications occurred immediately after surgery, and only
      two cases of capsular contracture Baker grade 2 cases with implant palpability
      occurred during a mean follow-up period of 18 months. All 17 women were very
      satisfied with the improvement in their clothed appearance, and 16 were very
      satisfied overall with their surgery and body image improvements. CONCLUSIONS:
      With proper selection of patients and Style 410 breast implants, cases of grade 3
      breast ptosis can be managed successfully by the periareolar approach, thus
      extending the range of cases suitable for this technique. The different shapes of
      the Style 410 form-stable, silicone gel implants help to recreate the desired
      natural-looking breast, achieving stable results with minimal complications.

PMID- 20043161
TI  - Transposition of the malpositioned nipple-areola complex in breast reconstruction
      with implants.
AB  - BACKGROUND: The goal of breast reconstruction after breast cancer is to obtain
      symmetrical breasts, including the nipple-areola complex. However, in some cases
      the nipple-areola complex may not be symmetrical even though a symmetrical breast
      shape has been created. In such cases the nipple-areola complex has been
      transpositioned, leaving a scar to close the wound or skin graft in the original
      position. METHODS: To treat this problem, skin surrounding the areola is removed
      and two pedicles are created to bear the nipple-areola complex. The nipple-areola
      complex is then moved to the proposed position and the surrounding circular edge
      of the skin is closed using a purse-string suture. RESULTS: The author performed
      this technique in three nipple-areolae of two patients. All the nipple-areolae
      were transposed to the proposed position to create symmetrical breasts without
      any complications. CONCLUSION: This technique can be used when the malpositioned
      nipple-areola complex is not too far from the proposed position. The nipple
      areola complex can be moved without leaving any scar at the original position of
      the complex.

PMID- 20043162
TI  - Hypo- and hypernatraemia in surgical patients: is there room for improvement?
AB  - BACKGROUND: Up to 30% of surgical inpatients develop complications related to
      fluid and electrolyte therapy. We sought to study the occurrence of hypo- and
      hypernatraemia in these patients to inform current standards of care. METHODS:
      This prospective audit took place over 80 days in a university hospital. Patients
      with a serum sodium concentration less than 130 or greater than 150 mmol/l were
      included. Daily intakes of Na(+), K(+) and Cl(-), and fluid balance were recorded
      before and after development of dysnatraemia. Fluid balance charts were assessed,
      as was the presence of documented patient weights. Patients were followed up
      until one of these milestones was reached: normonatraemia, death, or hospital
      discharge. RESULTS: During the study period 55 (4%) of the 1,383 surgical
      admissions met the inclusion criteria. Fifteen patients had hypernatraemia, 13
      (87%) of whom were identified on ICU/HDU. In the days preceding the
      hypernatraemia, patients received (in mmol/day) a median (IQR) of 157 (76-344)
      Na(+), 38 (6-65) K(+), 157 (72-310) Cl(-), and 1.96 (1.13-2.96) L water. In the
      days preceding the hyponatraemia, patients received 50 (0-189) Na(+), 0 (0-10)
      K(+), 56 (0-188) Cl(-), and 1.45 (0-2.60) L water. Before the dysnatraemias only
      28% of fluid balance charts were completed accurately. During the audit 42% of
      patients were not weighed. Dysnatraemic patients had a higher hospital mortality
      rate than those who did not develop dysnatraemia (12.7 vs. 2.3%, P < 0.001).
      CONCLUSIONS: Four percent of surgical inpatients developed dysnatraemias, which
      were associated with increased mortality. Fluid balance documentation was
      suboptimal and daily weights were not measured routinely, even in patients with
      severe electrolyte derangements.

PMID- 20043163
TI  - The middle thyroid vein: anatomical and surgical aspects.
AB  - BACKGROUND: An issue that has been overlooked in medical literature concerns the
      prevalence and topographic relationships of the middle thyroid vein (MTV), which
      have been studied, with a prospective approach, in patients with various thyroid
      diseases. METHODS: MTV prevalence has been investigated in 394 consecutive lobes
      and a number of different variables (age, gender, thyroid pathology, gland
      weight) have been considered. Moreover, in cooperation with our Human Morphology
      Department, we brought to completion a dedicated anatomy report, with the clear
      objective of providing a detailed anatomic description of MTV. RESULTS: The
      prevalence of MTV was 38% of the dissected lobes and 62% of operated patients.
      Most veins arise from the mid region of the thyroid lobe (80%): B, 3, and 2
      positions in accordance with our scheme. As far as thyroid pathology is
      concerned, we found that the presence of MTV was more frequent in hyperthyroidism
      and large goiters (p < 0.05). CONCLUSIONS: A better understanding of the anatomic
      variability in MTV may be useful not only to minimize the risk of bleeding, but
      it also can help to perform a more accurate dissection with the goal of
      preserving the laryngeal nerves and parathyroid glands, especially because of its
      location and relationships with other adjacent structures.

PMID- 20043164
TI  - How surgery taught me about media.

PMID- 20043166
TI  - Sunitinib in combination with docetaxel in patients with advanced solid tumors: a
      phase I dose-escalation study.
AB  - PURPOSE: Sunitinib in combination with docetaxel enhances antitumor activity in
      xenograft models of human breast and non-small cell lung cancer. We assessed the
      maximum tolerated doses (MTDs), safety, pharmacokinetic profiles, and preliminary
      efficacy of sunitinib plus docetaxel in patients with advanced solid tumors.
      METHODS: In this phase I study, successive patient cohorts received sunitinib 25,
      37.5, or 50 mg/day for 4 weeks of a 6-week cycle (Schedule 4/2, 4 weeks on, 2
      weeks off) or for 2 weeks of a 3-week cycle (Schedule 2/1, 2 weeks on, 1 week
      off) with docetaxel 60 or 75 mg/m(2) IV q21d to determine the MTDs of this
      treatment combination. RESULTS: Fifty patients enrolled: 10 on Schedule 4/2 and
      40 on Schedule 2/1. MTDs were established as sunitinib 25 mg on Schedule 4/2 with
      docetaxel 60 mg/m(2) q21d, and as sunitinib 37.5 mg on Schedule 2/1 with
      docetaxel 75 mg/m(2) q21d. On Schedule 2/1, the most frequent dose-limiting
      toxicity was neutropenia (+/-fever; grade [G]3/4, n = 5) and the most common G3/4
      non-hematologic adverse event (AE) was fatigue (G3, n = 8). Hematologic AEs were
      managed with growth factor support in 11 of 23 (48%) patients treated at Schedule
      2/1 MTD. Three patients achieved a partial response at the Schedule 2/1 MTD.
      There were no pharmacokinetic drug-drug interactions with either schedule.
      CONCLUSIONS: Oral sunitinib 37.5 mg/day on Schedule 2/1 with docetaxel 75 mg/m(2)
      IV q21d is a clinically feasible regimen with a manageable safety profile, no
      pharmacokinetic drug-drug interactions, and shows antitumor activity in patients
      with advanced solid tumors.

PMID- 20043167
TI  - Phenotypic and genetic characteristics of macrolide and lincosamide resistant
      Ureaplasma urealyticum isolated in Guangzhou, China.
AB  - The phenotypic and genetic characteristics of resistance to macrolides and
      lincosamides among 72 Ureaplasma urealyticum clinical strains isolated in
      Guangzhou, China were investigated in this study. Strains were studied by
      resistance phenotyping, detection of resistance genes (ermB, msrA, msrB, msrC,
      and msrD), and determining the significance of an association between the
      presence of resistance genes and the int-Tn gene (a genetic marker of
      transposon). The ermB, msrA, msrB, msrC, and msrD genes were obtained in 21, 1,
      12, 0, and 24 strains, respectively. The msrB and msrD genes were detected in
      strains of macrolides (M) or macrolides-streptogramin B (MS) resistance
      phenotype, and the ermB gene was detected in strains of M or macrolide
      lincosamide (ML) phenotype in U. urealyticum. Statistical analysis revealed that
      only the ermB gene was closely associated with the int-Tn gene. It was concluded
      that U. urealyticum harbored the ermB, msrA, msrB, and msrD genes which confer
      resistance to macrolides and (or) lincosamides. The ermB gene may be located in
      the U. urealyticum transposon.

PMID- 20043168
TI  - Deregulation of EZH2 expression in human spermatogenic disorders and testicular
      germ cell tumors.
AB  - INTRODUCTION: Enhancer of Zeste 2 (EZH2) is an epigenetic transcriptional
      repressor involved in cell cycle control and cell fate decisions. Since these
      processes play key roles during intact spermatogenesis, deregulation of EZH2
      expression may contribute to the development and progression of benign and
      malignant testicular diseases. The objective of this study was to investigate the
      expression profile of EZH2 in testicular germ cell tumors (TGCT) and
      spermatogenic defects. MATERIAL AND METHODS: Real-time RT-PCR was applied to
      quantify the m-RNA expression of EZH2 in 64 seminomas 36 non-seminomas, 4
      carcinomas in situ (CIS), 40 samples harboring impaired spermatogenesis and 24
      normal testicular reference biopsies. RESULTS: EZH2 was expressed in 99% of TGCT
      samples and in all biopsies with intact spermatogenesis. Its expression levels
      were highest in normal testicular tissue, and continuously decreased with
      malignant transformation to CIS and further progression to invasive TGCT (P <
      0.001). EZH2 tumor levels were not related to the histological TGCT subtype or
      clinical tumor stage. Comparison of distinct stages of spermatogenic failure
      revealed an inverse association of EZH2 levels to the severity of the
      spermatogenic defect (P < 0.001). CONCLUSION: Our data strongly suggest that in
      TGCT EZH2 does not exert its often assumed oncogenic properties during malignant
      transformation and progression. High EZH2 levels in normal testicular tissue and
      the inverse association of its expression levels with the severity of
      spermatogenic failure point to its potential value as a molecular marker for
      spermatogenic defects and may indicate an important physiological role of EZH2
      during intact spermatogenesis.

PMID- 20043169
TI  - Temporal lobe herniation of developmental origin: a novel radiological
      association with open spina bifida and Chiari II malformation.

PMID- 20043170
TI  - Effects of glycerol on human skin damaged by acute sodium lauryl sulphate
      treatment.
AB  - Glycerol, widely used as humectant, is known to protect against irritants and to
      accelerate recovery of irritated skin. However, most studies were done with
      topical formulations (i.e. emulsions) containing glycerol in relatively high
      amounts, preventing drawing conclusions from direct effects. In this study, acute
      chemical irritations were performed on the forearm with application of a 10%
      sodium lauryl sulphate (SLS) aqueous solution under occlusion for 3 h. Then,
      glycerol aqueous solutions from 1 to 10% were applied under occlusion for 3 h.
      After elimination of moist excess consecutive to occlusive condition, in ambient
      air for 15 and 30 min, skin barrier function was investigated by dual measurement
      of skin hydration and transepidermal water loss (TEWL). Treatments with SLS
      solution under occlusion significantly increased TEWL and decreased skin
      hydration as assessed by capacitance measurements. The SLS irritant property was
      raised by the occlusion and the water barrier function as well as water content
      appeared impaired. Recovery with glycerol at low doses was remarkable through a
      mechanism that implies its hygroscopic properties and which is saturable. This
      precocious effect acts through skin rehydration by enhancing water-holding
      capacity of stratum corneum that would facilitate the late physiological repair
      of impaired skin barrier. Thus, glycerol appears to substitute for natural
      moisturizing factors that have been washed out by the detergent action of SLS,
      enhancing skin hydration but without restoring skin barrier function as depicted
      by TEWL values that remained high. Thus, irritant contact dermatitis treated with
      glycerol application compensate for skin dehydration, favouring physiological
      process to restore water barrier function of the impaired skin. Empirical use of
      glycerol added topical formulations onto detergent altered skin was substantiated
      in the present physicochemical approach.

PMID- 20043171
TI  - Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in
      cultured sebocytes.
AB  - Acne is a complex, chronic and common skin disorder of pilosebaceous units.
      Hyperkeratinization of keratinocytes, increased sebum excretion from sebocytes
      via androgen stimulation and inflammatory cytokines are the major factors
      involved in the pathophysiology of acne. In addition, it is known that
      keratinocytes play an important role in acne synthesizing a number of
      inflammatory cytokines. However, the nature of the association between
      inflammatory cytokines and sebocytes in acne remains unclear. Culture of
      sebocytes provides a new insight into the participation of dihydrotestosterone
      (DHT) in the production of inflammatory cytokines in acne. To examine the
      possible involvement of DHT in the production of inflammatory cytokines in the
      cultured sebocytes, we used immunohistochemistry and RT-PCR to compare the
      expression of interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF
      alpha). Upregulation of IL-6 and TNF-alpha in immunohistochemistry, and increase
      in RNA amplification for IL-6 and TNF-alpha were observed after addition of DHT
      compared with the control. This study suggests that DHT may not only be involved
      in sebum production but also in production of proinflammatory cytokines in acne.

PMID- 20043172
TI  - Primary peritoneal carcinoma: a diagnostic dilemma.

PMID- 20043173
TI  - Chemosensory function in Wegener's granulomatosis: a preliminary report.
AB  - Despite the fact that Wegener's granulomatosis affects the nasal and paranasal
      cavities and the cranial nerves regularly, chemosensory impairments have not been
      reported. The objective of this study is to test the three chemosensory systems,
      olfaction, taste, and intranasal trigeminal function in Wegener disease patients.
      We tested olfactory, gustatory, and intranasal trigeminal function in nine
      patients (5 women, 4 men, mean age 57 years) with confirmed Wegener's
      granulomatosis. Olfaction was tested with the Sniffin'Sticks, gustatory function
      with the "Taste strips" and intranasal trigeminal function with a lateralization
      task. One patient had anosmia (11%), four patients had hyposmia (44%) and four
      patients were normosmic (45%). Gustatory testing function showed pathological
      taste strip results in five patients (55%) and normal results in three patients
      (33%). One patient did not undergo taste testing. Intranasal trigeminal function
      was lowered in five patients (56%) and normal in four patients (44%). Neither
      previous nasal surgery status nor endoscopic status was associated to a higher
      frequency in pathological scores for any of the three chemical senses. In
      conclusion, these preliminary results suggest a consistent affection in
      chemosensory functions in Wegener's granulomatosis patients.

PMID- 20043175
TI  - Influence of stimulus--response assignment on the joint-action correspondence
      effect.
AB  - Sebanz et al. (Cognition 88:B11-B21, 2003) have shown that spatial correspondence
      effects are observed even when the two-choice reaction time task is distributed
      between two people, such that each person is assigned only one of two possible
      stimulus-response (S-R) pairings. The effect is similar to when one person is
      assigned and responds to both S-R pairings. These results have been taken to
      suggest that two people performing a complementary task co-represent each other's
      response alternatives. In our experiment, we examined performance when paired
      participants responded to the same S-R alternative. We reasoned that co
      representation would be of little advantage as the task alternatives would be the
      same for both participants. Correspondence effects were absent when paired
      participants responded to the same S-R alternative but emerged when they
      responded to different alternatives.

PMID- 20043174
TI  - A genomics resource for investigating regulation of essential oil production in
      Lavandula angustifolia.
AB  - We are developing Lavandula angustifolia (lavender) as a model system for
      investigating molecular regulation of essential oil (a mixture of mono- and
      sesquiterpenes) production in plants. As an initial step toward building the
      necessary 'genomics toolbox' for this species, we constructed two cDNA libraries
      from lavender leaves and flowers, and obtained sequence information for 14,213
      high-quality expressed sequence tags (ESTs). Based on homology to sequences
      present in GenBank, our EST collection contains orthologs for genes involved in
      the 1-deoxy-D: -xylulose-5-phosphate (DXP) and the mevalonic acid (MVA) pathways
      of terpenoid biosynthesis, and for known terpene synthases and prenyl
      transferases. To gain insight into the regulation of terpene metabolism in
      lavender flowers, we evaluated the transcriptional activity of the genes encoding
      for 1-deoxy-D: -xylulose-5-phosphate synthase (DXS) and HMG-CoA reductase (HMGR),
      which represent regulatory steps of the DXP and MVA pathways, respectively, in
      glandular trichomes (oil glands) by real-time PCR. While HMGR transcripts were
      barely detectable, DXS was heavily expressed in this tissue, indicating that
      essential oil constituents are predominantly produced through the DXP pathway in
      lavender glandular trichomes. As anticipated, the linalool synthase (LinS)-the
      gene responsible for the production of linalool, a major constituent of lavender
      essential oil-was also strongly expressed in glands. Surprisingly, the most
      abundant transcript in floral glandular trichomes corresponded to a sesquiterpene
      synthase (cadinene synthase, CadS), although sesquiterpenes are minor
      constituents of lavender essential oils. This result, coupled to the weak
      activity of the MVA pathway (the main route for sesquiterpene production) in
      trichomes, indicates that precursor supply may represent a bottleneck in the
      biosynthesis of sesquiterpenes in lavender flowers.

PMID- 20043177
TI  - Ectoparasites, uropygial glands and hatching success in birds.
AB  - The uropygial gland of birds secretes wax that is applied to the plumage, where
      the secretions are hypothesized to eliminate fungi and bacteria, thereby
      potentially providing important benefits in terms of plumage maintenance. We
      analyzed variation in size of the uropygial gland in 212 species of birds to
      determine the function and the ecological correlates of variation in gland size.
      Bird species with larger uropygial glands had more genera of chewing lice of the
      sub-order Amblycera, but not of the sub-order Ischnocera, and more feather mites.
      There was a fitness advantage associated with relatively large uropygial glands
      because such species had higher hatching success. These findings are consistent
      with the hypothesis that the uropygial gland functions to manage the community of
      microorganisms, and that certain taxa of chewing lice have diverged as a
      consequence of these defenses.

PMID- 20043176
TI  - Molecular mechanisms of secondary imatinib resistance in patients with
      gastrointestinal stromal tumors.
AB  - AIMS AND BACKGROUND: Most gastrointestinal stromal tumor (GIST) patients respond
      to KIT inhibition therapy of imatinib, but eventually become resistant with a
      median time to progression of 2 years. The mechanism of acquired resistance to
      imatinib and oncogenic KIT signal transduction in GISTs has not been well
      defined. We sought to investigate the spectrum of molecular and genomic changes
      in imatinib-resistant GIST patients. METHODS: KIT and PDGFRA mutations were
      evaluated in 48 samples obtained from 32 GIST patients who underwent surgery
      after imatinib treatment. KIT downstream signaling profiles were also
      investigated in eight specimens of five patients who were clinically responsive
      or resistant to imatinib therapy. Biochemical inhibition of KIT, mitogen
      activated protein kinase (MAPK), mammalian target of rapamycin (MTOR), AKT,
      proliferating cell nuclear antigen (PCNA) and BCL-2 were determined by western
      blotting for protein activation. RESULTS: In all 32 GIST patients, activating
      mutations in the KIT gene were seen in 26 (81.3%) patients, PDGFRA gene mutations
      were seen in 2 (6.2%) patients and no primary mutations were found in 4 (12.5%)
      patients. Secondary KIT mutations were identified in 11/14 (78.6%) imatinib
      acquired-resistance patients, with nine patients in KIT gene exon17, and the
      other two in exon 13. The expressions of p-KIT, p-AKT, PCNA and BCL-2 were higher
      in the samples of imatinib-resistant GISTs than those of imatinib-responsive
      ones. P-KIT, p-AKT expressions were higher in imatinib acquired-resistance GISTs
      with secondary KIT mutations than imatinib-responsive ones with primary mutation.
      Total KIT, MAPK, p-MAPK, p-MTOR expressions were comparable in all varied GISTs.
      CONCLUSIONS: Novel additional mutations of KIT gene exon 13 or exon 17 indicate
      the likely mechanism of secondary resistance to imatinib. The PI3-K/AKT pathway
      might be more relevant than MEK/MAPK for therapeutic targeting in imatinib
      resistant GIST patients with secondary mutation.

PMID- 20043178
TI  - Temporal differences in food abundance promote coexistence between two congeneric
      passerines.
AB  - Many related species share the same environment and utilize similar resources.
      This is surprising because based on the principle of competitive exclusion one
      would predict that the superior competitor would drive the other species to
      extinction; coexistence is only predicted if interspecific competition is weaker
      than intraspecific competition. Interspecific competition is frequently reduced
      by differential resource use, resulting in habitat segregation. In this paper, we
      use the closely related collared and pied flycatcher to assess the potential of
      habitat differences to affect interspecific competition through a different
      mechanism, namely by generating temporal differences in availability of similar
      food resources between the two species. We found that the tree species
      composition of the breeding territories of the two species differed, mainly by a
      higher abundance of coniferous species around nest-boxes occupied by pied
      flycatchers. The temporal availability of caterpillars was measured using frass
      traps under four deciduous and two coniferous tree species. Deciduous tree
      species showed an early and narrow peak in abundance, which contrasted with the
      steady increase in caterpillar abundance in the coniferous tree species through
      the season. We subsequently calculated the predicted total caterpillar biomass
      available in each flycatcher territory. This differed between the species, with
      biomass decreasing more slowly in pied flycatcher territories. Caterpillar
      biomass is strongly correlated with the reproductive success of collared
      flycatchers, but much less so with pied flycatchers. However, caterpillar
      availability can only partly explain the differences in seasonal decline of
      reproductive success between the two species; we discuss additional factors that
      may contribute to this species difference. Overall, our results are consistent
      with the suggestion that minor habitat differences between these two species may
      contribute to promoting their coexistence.

PMID- 20043179
TI  - Bias and uncertainty of delta13CO 2 isotopic mixing models.
AB  - Patterns in the isotopic signal (stable C isotope composition; delta(13)C) of
      respiration (delta(13)C(R)) have led to important gains in understanding the C
      metabolism of many systems. Contained within delta(13)C(R) is a record of the C
      source mineralized, the metabolic pathway of C and the environmental conditions
      during which respiration occurred. Because gas samples used for analysis of
      delta(13)C(R) contain a mixture of CO(2) from respiration and from the
      atmosphere, two-component mixing models are used to identify delta(13)C(R).
      Measurement of ecosystem delta(13)C(R), using canopy airspace gas samples, was
      one of the first applications of mixing models in ecosystem ecology, and thus
      recommendations and guidelines are based primarily on findings from these
      studies. However, as mixing models are applied to other experimental conditions
      these approaches may not be appropriate. For example, the range in [CO(2)]
      obtained in gas samples from canopy air is generally less than 100 micromol mol(
      1), whereas in studies of respiration from soil, foliage or tree stems, the range
      can span as much as 10,000 micromol mol(-1) and greater. Does this larger range
      in [CO(2)] influence the precision and accuracy of delta(13)C(R) estimates
      derived from mixing models? Does the outcome from using different regression
      approaches and mixing models vary depending on the range of [CO(2)]? Our research
      addressed these questions using a simulation approach. We found that it is
      important to distinguish between large (>1,000 micromol mol(-1)) and small (<100
      micromol mol(-1)) ranges of CO(2) when applying a mixing model (Keeling plot or
      Miller-Tans) and regression approach (ordinary least squares or geometric mean
      regression) combination to isotopic data. The combination of geometric mean
      regression and the Miller-Tans mixing model provided the most accurate and
      precise estimate of delta(13)C(R) when the range of CO(2) is >or=1,000 micromol
      mol(-1).

PMID- 20043180
TI  - Consistently inconsistent: commercially available starch-based dysphagia
      products.
AB  - Individuals with dysphagia may be prescribed thickened fluids to promote a safer
      and more successful swallow. Starch-based thickening agents are often employed;
      however, these exhibit great variation in consistency. The aim of this study was
      to compare viscosity and the rheological profile parameters complex (G*), viscous
      (G"), and elastic modulus (G') over a range of physiological shear rates. UK
      commercially available dysphagia products at "custard" consistency were examined.
      Commercially available starch-based dysphagia products were prepared according to
      manufacturers' instructions; the viscosity and rheological parameters were tested
      on a CVOR Rheometer. At a measured shear rate of 50 s(-1), all products fell
      within the viscosity limits defined according to the National Dysphagia Diet Task
      Force guidelines. However, at lower shear rates, large variations in viscosity
      were observed. Rheological parameters G*, G', and G" also demonstrated
      considerable differences in both overall strength and rheological behavior
      between different batches of the same product and different product types. The
      large range in consistency and changes in the overall structure of the starch
      based products over a range of physiological shear rates show that patients could
      be receiving fluids with very different characteristics from that advised. This
      could have detrimental effects on their ability to swallow.

PMID- 20043182
TI  - Capillary dimension measured by computer-based digitalized image correlated with
      plasma endothelin-1 levels in patients with systemic sclerosis.
AB  - Endothelial and vascular damage are main leading disability in systemic sclerosis
      (SSc). Raynaud's phenomenon is the early symptom that presents vascular damage.
      Nailfold capillaroscopy (NFC) is an easily accessible diagnostic tool in
      secondary Raynaud's phenomenon. Considering the endothelial damage, clinical
      manifestations, and plasma cytokines was compared with traditionally used NFC
      parameter for, which to observe the number of capillaries, deletions in 3 mm,
      apical limb width and the capillary width itself. We hypothesize that a computer
      based NFC system can generate a new powerful parameter which predicts the
      capillary dimension. We investigated the relationship among the plasma endothelin
      1 (ET-1), clinical manifestations and quantitative analysis of computerized NFC,
      and to assess the optimal method in SSc. The level of ET-1 in 60 SSc patients, 30
      healthy, and 23 disease controls were measured by enzyme-linked immunosorbent
      assay (ELISA) kit. We present a significant difference in all parameters of NFC
      between SSc patients and control groups. ET-1 level was increased in patients
      with SSc. In SSc group, capillary dimension and loss of capillaries were strongly
      associated with digital ulceration (p < 0.01) and pulmonary hypertension (p <
      0.05). Capillary dimension and ET-1 level was in correlation with skin-hardening
      grade, and was higher in SSc patients with pulmonary hypertension or digital
      ulcer. Capillary dimension showed strong correlation with the endothelin-1 in
      SSc, healthy and disease control groups. (Rs = 0.31/p < 0.05, Rs = 0.82/p <
      0.001, Rs = 0.83/p < 0.001). The results suggest that computer-based microscopic
      analysis of NFC is a useful method that potentially provides information on organ
      involvement and plasma ET-1. Capillary dimension maybe a powerful parameter
      possibly applicable in outpatient clinic for assessing SSc patients.

PMID- 20043183
TI  - Catestatin, an endogenous chromogranin A-derived peptide, inhibits in vitro
      growth of Plasmodium falciparum.
AB  - Catestatin, an endogenous peptide derived from bovine chromogranin A, and its
      active domain cateslytin display powerful antimicrobial activities. We have
      tested the activities of catestatin and other related peptides on the growth of
      Plasmodium falciparum in vitro. Catestatin inhibits growth of the chloroquine
      sensitive strain of P. falciparum 3D7, exhibiting 88% inhibition at 20 microM. A
      similar partial inhibition of parasite growth was observed for the chloroquine
      resistant strain, 7G8 (64%,) and the multidrug-resistant strain, W2 (62%). In the
      presence of parasite-specific lactate dehydrogenase, a specific protein-protein
      interaction between catestatin and plasmepsin II precursor was demonstrated. In
      addition, catestatin partially inhibited the parasite-specific proteases
      plasmepsin in vitro. A specific interaction between catestatin and plasmepsins II
      and IV from P. falciparum and plasmepsin IV from the three remaining species of
      Plasmodium known to infect man was observed, suggesting a catestatin-induced
      reduction in availability of nutrients for protein synthesis in the parasite.

PMID- 20043184
TI  - Timing is everything: the regulation of type III secretion.
AB  - Type Three Secretion Systems (T3SSs) are essential virulence determinants of many
      Gram-negative bacteria. The T3SS is an injection device that can transfer
      bacterial virulence proteins directly into host cells. The apparatus is made up
      of a basal body that spans both bacterial membranes and an extracellular needle
      that possesses a channel that is thought to act as a conduit for protein
      secretion. Contact with a host-cell membrane triggers the insertion of a pore
      into the target membrane, and effectors are translocated through this pore into
      the host cell. To assemble a functional T3SS, specific substrates must be
      targeted to the apparatus in the correct order. Recently, there have been many
      developments in our structural and functional understanding of the proteins
      involved in the regulation of secretion. Here we review the current understanding
      of protein components of the system thought to be involved in switching between
      different stages of secretion.

PMID- 20043186
TI  - Vegetative state: efforts to curb misdiagnosis.
AB  - Media reports on the case of Rom Houben have constituted a new reminder of the
      risks of misdiagnosis with cases with apparent vegetative state, particularly
      when following the clinical consensus of the care team as diagnostic criterion.
      Systematic use of behavioral and non-behavioral assessment strategies (e.g.,
      behavioral scales, event-related potentials, and neuro-imaging) may help reduce
      the aforementioned risks. A new learning assessment strategy could also be
      considered part of the assessment to extend the evaluation process. Signs of
      learning might be viewed as forms of concrete knowledge representing a basic
      level of non-reflective consciousness.

PMID- 20043187
TI  - Working memory components in survey and route spatial text processing.

PMID- 20043188
TI  - A comparison of multifocal ERG and frequency domain OCT changes in patients with
      abnormalities of the retina.
AB  - To compare the ability of the multifocal electroretinogram (mfERG) and frequency
      domain optical coherence tomography (fdOCT) to detect retinal abnormalities. A
      total of 198 eyes (100 patients) were referred by neuro-ophthalmologists to rule
      out a retinal etiology of visual impairment. All patients were evaluated with
      static automated perimetry (SAP) (Humphrey Visual Field Analyzer; Zeiss Meditec),
      mfERG (Veris, EDI) and fdOCT (3D-OCT 1000, Topcon). The mfERG was performed with
      103 scaled hexagons and procedures conforming to ISCEV standards (Hood DC et al.
      (2008) Doc Ophthalmol 116(1):1-11). The fdOCT imaging included horizontal and
      vertical line scans through the fovea. Local mfERG and fdOCT abnormalities were
      compared to local regions of visual field sensitivity loss measured with SAP and
      categorized as normal/inconclusive or abnormal. 146 eyes were categorized as
      normal retina on both fdOCT and mfERG. The retina of 52 eyes (36 patients) was
      categorized as abnormal based upon mfERG and/or fdOCT. Of this group, 25 eyes (20
      patients) were abnormal on both tests. However, 20 eyes (13 patients) were
      abnormal on mfERG, while the fdOCT was normal/inconclusive; and 7 eyes (7
      patients) had normal or inconclusive mfERG, but abnormal fdOCT. Considerable
      disagreement exists between these two methods for detection of retinal
      abnormalities. The mfERG tends to miss small local abnormalities that are
      detectable on the fdOCT. On the other hand, the fdOCT can appear normal in the
      face of clearly abnormal mfERG and SAP results. While improved imaging and
      analysis may show fdOCT abnormalities in some cases, in others early damage may
      not appear on structural tests.

PMID- 20043185
TI  - From protein sequences to 3D-structures and beyond: the example of the UniProt
      knowledgebase.
AB  - With the dramatic increase in the volume of experimental results in every domain
      of life sciences, assembling pertinent data and combining information from
      different fields has become a challenge. Information is dispersed over numerous
      specialized databases and is presented in many different formats. Rapid access to
      experiment-based information about well-characterized proteins helps predict the
      function of uncharacterized proteins identified by large-scale sequencing. In
      this context, universal knowledgebases play essential roles in providing access
      to data from complementary types of experiments and serving as hubs with cross
      references to many specialized databases. This review outlines how the value of
      experimental data is optimized by combining high-quality protein sequences with
      complementary experimental results, including information derived from protein 3D
      structures, using as an example the UniProt knowledgebase (UniProtKB) and the
      tools and links provided on its website ( http://www.uniprot.org/ ). It also
      evokes precautions that are necessary for successful predictions and
      extrapolations.

PMID- 20043189
TI  - Secondary fibrosarcoma of the brain stem treated with cyclophosphamide and
      Imatinib.
AB  - Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which
      is associated with poor prognosis. We present the case of a 48-year old man with
      brainstem fibrosarcoma 20 years following radiation therapy received for a
      pituitary tumor. We discuss this case in the context of the diagnostic criteria
      for these tumors, and previous reports of secondary and primary sarcomas of the
      central nervous system.

PMID- 20043190
TI  - Prognostic factors in pediatric high-grade astrocytoma: the importance of
      accurate pathologic diagnosis.
AB  - To characterize a population of pediatric high-grade astrocytoma (HGA) patients
      by confirming the proportion with a correct diagnosis, and determine prognostic
      factors for survival in a subset diagnosed with uniform pathologic criteria.
      Sixty-three children diagnosed with HGA were treated at the Johns Hopkins
      Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all
      available histologic samples (n = 48). Log-rank analysis was used to compare
      survival by patient, tumor, and treatment factors. Median follow-up was 16 months
      for all patients and 155 months (minimum 54 months) for surviving patients.
      Median survival for all patients (n = 63) was 14 months with 10 long-term
      survivors (survival >48 months). At initial diagnosis, 27 patients were grade III
      (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available
      for review, including seven of ten long-term surviving patients. Four patients
      had non-HGA pathology, all of whom were long term survivors. The remaining 44
      patients with confirmed HGG had a median survival of 14 months and prognostic
      analysis was confined to these patients. On multivariate analysis, five factors
      were associated with inferior survival: performance status (Lansky) <80% (13 vs.
      15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16
      months), resection less than gross total (13 vs. 22 months), and radiotherapy
      dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five
      adverse factors (n = 27), median survival and proportion of long-term survivors
      were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1
      adverse factors (n = 17). In an historical cohort of children with HGA, the
      potential for long term survival was confined to the subset with less than two of
      the following adverse prognostic factors: low performance status, bilaterality,
      parietal lobe site, less than gross total resection, and radiotherapy dose <50
      Gy. Pathologic misdiagnosis should be suspected in patients who are long term
      survivors of a pediatric high grade astrocytoma.

PMID- 20043191
TI  - Overexpression of Trpp5 contributes to cell proliferation and apoptosis probably
      through involving calcium homeostasis.
AB  - Trpp5 is one member of the polycystic kidney disease (PKD) family, which belongs
      to transient receptor potential (TRP) superfamily. Our previous study has shown
      that Trpp5 is developmentally expressed in mouse testis and overexpression of
      Trpp5 increases intracellular free calcium concentration in MDCK cells. However,
      the roles of this protein in cellular processes are largely unknown. Here, we
      demonstrated that Trpp5 resided in both cytoplasm and cell membrane of HEK293
      cells. We found that overexpression of Trpp5 slightly increased the calcium
      current amplitude of HEK293 cells and shifted the reversal potential to a more
      negative value. Meanwhile, overexpression of Trpp5 suppressed proliferation of
      Hela cells via inhibiting DNA replication and induced apoptosis of Hela cells
      with morphological changes and accumulation of fragmented DNA. Collectively,
      these findings suggest that Trpp5 might involve calcium homeostasis contributing
      to cell proliferation and apoptosis.

PMID- 20043192
TI  - Involvement of the residues of GSKIP, AxinGID, and FRATtide in their binding with
      GSK3beta to unravel a novel C-terminal scaffold-binding region.
AB  - The specificity and regulation of GSK3beta are thought to involve in the docking
      interactions at core kinase domain because of the particular amino acid residues.
      Recent X-ray diffraction studies illuminated the relative binding residues on
      AxinGID and FRATtide for GSK3beta docking and appeared that GSK3beta Val267Gly
      (V267G) and Tyr288Phe (Y288F) could distinguish the direct interaction between
      AxinGID and FRATtide. In order to explore the mode that involved the binding of
      GSKIP to GSK3beta and compare it with that of AxinGID and FRATtide, we pinpointed
      the binding sites of GSKIP to GSK3beta through the single-point mutation of four
      corresponding sites within GSK3beta (residues 260-300) as scaffold-binding region
      I (designated SBR-I(260-300)). Our data showed that these three binding proteins
      shared similar binding sites on GSK3beta. We also found that the binding of
      GSK3beta V267G mutant to GSKIP and AxinGID, but not that of Y288F mutant (effect
      on FRATtide), was affected. Further, based on the simulation data, the electron
      density map of GSKIPtide bore closer similarity to the map AxinGID than to that
      of FRATtide. Interestingly, many C-terminal helix region point-mutants of
      GSK3beta L359P, F362A, E366K, and L367P were able to eliminate the binding with
      FRATtide, but not AxinGID or GSKIP. In addition, CABYR exhibited a unique mode in
      binding to C-terminal helix region of GSK3beta. Taken together, our data revealed
      that in addition to the core kinase domain, SBR-I(260-300), another novel C
      terminus helix region, designated SBR-II(339-383), also appeared to participate
      in the recognition and specificity of GSK3beta in binding to other specific
      proteins.

PMID- 20043193
TI  - Bioactive long-term release from biodegradable microspheres preserves implanted
      ALG-PLO-ALG microcapsules from in vivo response to purified alginate.
AB  - PURPOSE: To assess whether prevention of unexpected in vivo adverse inflammatory
      and immune responses to biohybrid organ grafts for the treatment of Type I
      Diabetes Mellitus (T1DM) is possible by superoxide dismutase and ketoprofen
      controlled release. METHODS: Superoxide dismutase and ketoprofen-loaded polyester
      microspheres were prepared by W/O/W and O/W methods, embodied into purified
      alginate-poly-L-ornithine-alginate microcapsules and intraperitoneally implanted
      into CD1 mice. The microspheres were characterized for morphology, size,
      encapsulation efficiency, enzyme activity and in vitro release. Purified alginate
      contaminants were assayed, and the obtained microcapsules were investigated for
      size and morphology before and after implantation over 30 days. Cell pericapsular
      overgrowth and expression were evaluated by optical microscopy and flow
      cytometry. RESULTS: Superoxide dismutase and ketoprofen sustained release reduced
      cell pericapsular overgrowth in comparison to the control. Superoxide dismutase
      release allowed preserving the microcapsules over 30 days. Ketoprofen-loaded
      microspheres showed some effect in the immediate post-grafting period. A higher
      macrophage and T-cell expression was observed for the control group. CONCLUSIONS:
      Microspheres containing superoxide dismutase and ketoprofen may represent novel
      tools to limit or prevent unpredictable adverse in vivo response to alginate,
      thus contributing to improve cell transplantation success rates in T1DM
      treatment.

PMID- 20043194
TI  - 'Bad' boys and 'sad' girls? Examining internalizing and externalizing effects on
      parasuicides among youth.
AB  - Suicide and parasuicides (i.e. suicidal ideation and suicidal attempt) have long
      been recognized as serious social problems, especially among youth. A series of
      logistic regression models were developed incorporating various internalizing and
      externalizing risk factors experienced by young people with the goal of
      predicting parasuicides among Canadian youth. The main objective of the research
      is to determine whether or not there are significant sex differences between
      these internalizing and externalizing influences on suicidal behavior. Data were
      used from the National Longitudinal Study of Children and Youth-Waves 3 through
      6, for a total sample of 2,499 15-year olds (48.9% male). Results show that both
      suicidal ideation and attempt are more frequent for girls compared to boys.
      Contrary to expectations, externalizing problems had a greater impact on girls
      and internalizing problems had a marginally greater impact on boys. This casts
      doubt on the notion that "bad boys" and "sad girls" are at greater risk for
      suicidal behavior. These results are discussed in light of their substantive
      importance, policy implications, and suggestions for future research.

PMID- 20043195
TI  - Sequence characterization of cotton leaf curl virus from Rajasthan: phylogenetic
      relationship with other members of geminiviruses and detection of recombination.
AB  - Diseased cotton plants showing typical leaf curl symptoms were collected from
      experimental plot of Agriculture Research Station-Sriganganagar, Rajasthan.
      Complete DNA-A component from samples taken from two areas were amplified through
      rolling circle amplification (RCA) using templiphi kit (GE Healthcare) and
      characterized. DNA-A of one isolate consists of 2751 nucleotides and second
      isolate of 2759 nucleotide. Both sequences comprised six ORF's. Genome
      organization of DNA-A of one isolate shows high sequence similarity with other
      characterized local begomovirus isolates of Rajasthan, while other isolate shows
      high sequence similarity with CLCuV reported from Pakistan. The maximum
      similarity of first isolate, CLCuV-SG01, shows highest sequence identity with
      Cotton leaf curl Abohar (Rajasthan) virus, and second isolate, CLCuV-SG02, shows
      highest sequence identity with cotton leaf curl virus from Pakistan. Both
      isolates showed 85% similarities with each other. The sequence data revealed
      probable infiltration of some strains of Cotton leaf curl virus from Pakistan to
      India, or co-existence of different isolates under similar geographical
      conditions. While CLCuV-SG01 shows highest nt sequence similarity with CLCuV
      Rajasthan (Abohar), nt identity of V1 ORF (encoding coat protein) of SG01 shows
      the highest nt identity (100%) with CLCuV Multan (Bhatinda) and Abohar virus
      while AC1 region also showed difference. Complete nucleotide sequence of SG01
      shows only 86% similarity with CLCuV Multan virus. Similarity search revealed
      significant difference in AV1 and AC1 regions with respect to DNA-A suggesting an
      evolutionary history of recombination. Computer based analysis, recombination
      detection Program (RDP) supports the recombination hypothesis, indicated that
      recombination with other begomoviruses had taken place within V1 ORF and AC1 ORF
      of CLCuV-SG01 and AC1 ORF of CLCuV-SG02 and also in noncoding intergenic region
      (IR).

PMID- 20043196
TI  - Genetic analysis of porcine circovirus type 2 (PCV2) strains isolated between
      2001 and 2009: genotype PCV2b predominate in postweaning multisystemic wasting
      syndrome occurrences in eastern China.
AB  - Porcine circovirus type 2 (PCV2) is the essential infectious agent of postweaning
      multisystemic wasting syndrome (PMWS). In the present study, we obtained
      sequences of 31 PCV2 isolates from different farms of 11 provinces of eastern
      China and analyzed the genetic characterization of 136 eastern China-derivate
      PCV2 isolated during 2001-2009. The results showed that these PCV2 isolates could
      be divided into two groups, PCV2b (108 of 1A/1B, 19 of 1C) and PCV2a (1 of 2A, 2
      of 2D, 6 of 2E). Among the 9 PCV2a isolates, eight were found before the year
      2005. Meanwhile, three major heterogenic regions were observed in amino acid
      positions 53-91, 121-151, and 190-210; a few specific substitution patterns were
      found in each subgroup and several variant or conserved epitopes were also
      observed in the Cap protein. It indicated that PCV2b predominated in PMWS
      occurrences in eastern China and a few recombinants of different genotypes
      existed in nature.

PMID- 20043197
TI  - Molecular and biological characterization of a Marek's disease virus field strain
      with reticuloendotheliosis virus LTR insert.
AB  - A Marek's disease virus (MDV) field strain designated GX0101 was isolated from a
      layer flock and confirmed to be a recombinant virus with an insert of a long
      terminal repeat (LTR) from the reticuloendotheliosis virus (REV). A chimeric
      molecule containing an REV-LTR insert of 539 bp and its flanking sequences from
      MDV was amplified and sequenced. An REV-LTR downstream from the Internal Repeat
      Short (IRS) region has 77.4-98.6% homology to seven REV field strains isolated
      from different avian species in different parts of the world. The insertion site
      is located downstream of SORF 1 and upstream of SORF2 in the IRS region near the
      junction with the Unique Short (US) region in the MDV serotype 1 genome. Chicken
      experiments were conducted to determine the oncogenicity of the recombinant
      GX0101 virus and its transmissibility to contact chickens. Dot blot hybridization
      was used to detect the presence of the pp38 gene in feather tips from GX0101 or
      Md5 infected and contact birds. The pp38 was detected in GX0101 contact birds
      about 1-2 weeks earlier than in Md5 birds when both groups were vaccinated with
      HVT vaccine. Long term pathogenicity tests in specific pathogen free (SPF)
      chickens reveal that the recombinant GX0101 has a higher virulence than GA, but
      less virulence than Md5, the very virulent pathotype of MDV. This is the first
      report on an oncogenic serotype 1 MDV field strain with LTR insert and its
      pathogenicity.

PMID- 20043198
TI  - Phylogenetic and pathogenic analysis of Newcastle disease virus isolated from
      house sparrow (Passer domesticus) living around poultry farm in southern China.
AB  - House sparrow (Passer domesticus) is one of the most widely distributed wild
      birds in China. Five Newcastle disease virus (NDV) strains were isolated from
      house sparrows living around the poultry farms in southern China. These isolates
      were characterized by pathogenic assays and phylogenetic analysis. The results
      showed that all NDV isolates except one were velogenic and virulent for chickens.
      These four virulent strains for chickens possess the amino acid sequence (112)R/K
      R-Q-K/R-R-F(117) in the F(0) cleavage site which is typical of velogenic NDV.
      Phylogenetic analysis indicated that these isolates belong to genotype VII and
      were closely related to the strains which were isolated from NDV outbreaks in
      chickens since 2000. One isolate of NDV from house sparrow belong to genotype II
      and was proved to be vaccine strain (Chicken/U.S./LaSota/46). The result of this
      study proved that house sparrow can carry the virulent NDV strains and the same
      genotype of viruses that are circulating in poultry are existing in house
      sparrows living around poultry farm in southern China.

PMID- 20043199
TI  - Are females more responsive to emotional stimuli? A neurophysiological study
      across arousal and valence dimensions.
AB  - Men and women seem to process emotions and react to them differently. Yet, few
      neurophysiological studies have systematically investigated gender differences in
      emotional processing. Here, we studied gender differences using Event Related
      Potentials (ERPs) and Skin Conductance Responses (SCR) recorded from participants
      who passively viewed emotional pictures selected from the International Affective
      Picture System (IAPS). The arousal and valence dimension of the stimuli were
      manipulated orthogonally. The peak amplitude and peak latency of ERP components
      and SCR were analyzed separately, and the scalp topographies of significant ERP
      differences were documented. Females responded with enhanced negative components
      (N100 and N200), in comparison to males, especially to the unpleasant visual
      stimuli, whereas both genders responded faster to high arousing or unpleasant
      stimuli. Scalp topographies revealed more pronounced gender differences on
      central and left hemisphere areas. Our results suggest a difference in the way
      emotional stimuli are processed by genders: unpleasant and high arousing stimuli
      evoke greater ERP amplitudes in women relatively to men. It also seems that
      unpleasant or high arousing stimuli are temporally prioritized during visual
      processing by both genders.

PMID- 20043200
TI  - Predictors of unrecognized HIV infection among poor and ethnic men who have sex
      with men in Los Angeles.
AB  - This study evaluates associations between unrecognized HIV infection and
      demographic factors, internalized homonegativity, drug use, and sexual behaviors
      among HIV positive men who have sex with men (MSM). We analyzed data from 347 HIV
      positive participants from the Los Angeles site for NIDA's Sexual Acquisition and
      Transmission of HIV-Cooperative Agreement Program. Participants were HIV positive
      MSM and MSM/W and predominantly African American (36.0%) or Latino (38.7%), and
      unemployed (82.8%). Results from a multivariate logistic regression suggest that,
      compared to HIV positive participants who correctly reported their HIV positive
      status, being African-American (OR: 9.81, CI: 1.2-77.9) or Latino (OR: 10.92, CI:
      1.3-88.4) rather than White, MSM/W rather than MSM (OR: 3.24, CI: 1.09-9.62), and
      having higher homonegativity scores (OR: 1.22, CI: 1.02-1.4) is associated with
      unrecognized HIV infection, controlling for age, education, and homelessness.
      Findings provide some immediate evidence to help craft HIV prevention
      interventions.

PMID- 20043201
TI  - Weight change patterns among breast cancer survivors: results from the Shanghai
      breast cancer survival study.
AB  - In a population-based cohort study of 5,014 women with stage 0-III breast cancer,
      we evaluated weight change patterns from diagnosis to 6, 18, and 36 months post
      diagnosis. Patients were recruited to the study approximately 6 months after
      cancer diagnosis between 2002 and 2006 and followed through 36 months post
      diagnosis. The medians of weight change from diagnosis to 6, 18, and 36 months
      post-diagnosis were 1.0, 2.0, and 1.0 kg, respectively. Approximately, 26% of
      survivors gained > or =5% of their at-diagnosis body weight during the first 6
      months after diagnosis, while 37% and 33% of women gained the same percentage of
      weight at 18 and 36 months post-diagnosis. More weight gain was observed among
      women who had a more advanced disease stage, were younger, had lower body mass
      index at diagnosis, were premenopausal, or received chemotherapy or radiotherapy
      during the first 6 months after cancer diagnosis. Multivariate analyses indicated
      that age at diagnosis, body size, comorbidity, and disease stage independently
      predicted weight gain from diagnosis to 36 months post-diagnosis. In summary,
      weight gain is common over the first 3 years after breast cancer diagnosis among
      Chinese women. More research is needed to investigate measures to prevent weight
      gain in breast cancer survivors.

PMID- 20043202
TI  - Minerals and vitamins and the risk of bladder cancer: results from the New
      Hampshire Study.
AB  - OBJECTIVE: Although the effect of fruit and vegetables on the risk of bladder
      cancer has been widely studied, little is known about their micronutrient
      components. Our aim was to investigate associations between minerals and vitamins
      and bladder cancer. METHODS: A case-control study was conducted in New Hampshire,
      USA. Dietary data were collected from 322 cases and 239 controls using a 121-item
      food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated using logistic regression adjusting for sex, age, smoking
      characteristics, and energy intake. RESULTS: The ORs (95% CI) for highest
      quartile versus lowest quartile for total intake of vitamin E was 0.66 (0.36
      1.20; p trend = 0.09) and 0.49 (0.21-1.17; p trend = 0.13) for dietary
      phosphorus. The odds of bladder cancer for heavy smokers with the highest total
      intake of vitamin E, carotenoids, and niacin were 0.58 (0.34-0.99), 0.62 (0.36
      1.09), and 0.66 (0.39-1.14), respectively. Higher total intakes of carotenoids,
      vitamin D, thiamin, niacin, and vitamin E were inversely related to bladder
      cancer risk among older individuals. CONCLUSION: Our findings suggest further
      investigation of the effect of vitamin E, carotenoids, vitamin D, thiamin, and
      niacin on bladder cancer risk may be warranted. Future studies should focus on
      high risk groups such as heavy smokers and older individuals.

PMID- 20043203
TI  - Timeliness and follow-up patterns of cervical cancer detection in a cohort of
      medically underserved California women.
AB  - INTRODUCTION: This study examines factors associated with timely follow-up after
      Pap test in a program providing cervical cancer detection services to medically
      underserved California women. METHODS: Data between 01 January 1992 and 30 June
      2007 were analyzed. Cox proportional hazard regression was used to identify
      subgroups of women with delayed time to diagnosis or treatment scheduling. The
      probability of being scheduled for final diagnosis and treatment was assessed
      using logistic regression analysis. Demographic and clinical characteristics of
      the women lost to follow up were examined. RESULTS: Time from screening to final
      diagnosis scheduling differed according to age group, race/ethnicity, and Pap
      test result. Race/ethnicity and age were associated with whether treatment was
      scheduled or not. While loss to follow up among those scheduled for final
      diagnosis was associated with certain patients' characteristics, no such
      association was found among those who were scheduled for treatment. CONCLUSIONS:
      Patient's demographic characteristics determine the odds of being scheduled for
      final diagnosis and treatment as well as timeliness of follow-up from screening
      to final diagnosis. Findings suggest that the dual goal of reducing health
      disparities and cost-effective detection and treatment of precancerous disease to
      prevent cervical cancers cannot be achieved without consideration of
      racial/ethnic differences and needs.

PMID- 20043204
TI  - Divalproex sodium-ER in outpatients with disruptive behavior disorders: a three
      month open label study.
AB  - This aim of this clinical trial was to study the effects of divalproex sodium
      (DVPX) in reducing Reactive/Affective/ Defensive/ Impulsive Aggression (RADI) in
      youth with Disruptive Behavior Disorders (DBD) in an outpatient clinic over a
      period of 3 months. We recruited forty participants with Oppositional Defiant
      Disorder or Conduct Disorder. Twenty participants received 12 weeks of openly
      titrated DVPX, whereas twenty participants served as a comparison control group.
      Primary efficacy measures were the Clinical Global Improvement-Severity (CGI-S)
      and CGI-C (Change) scales; secondary efficacy measures included standardized
      measures of aggression. Based on the CGI-S and CGI-C ratings, the DVPX group
      showed significant improvement by the last observation. Attrition rates were
      notably high, which is not surprising given the clinical population studied. This
      study provides further support for the efficacy of DVPX in decreasing RADI
      aggression in the context of DBD. These results are particularly noteworthy
      because the sociotherapeutic structures supporting patients in previous trials
      were not present.

PMID- 20043205
TI  - Lack of an association between a functional polymorphism in the interleukin-6
      gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects.
AB  - The association between a single-nucleotide polymorphism (SNP) -174G > C
      (rs1800795) located in the IL-6 gene promoter and breast cancer risk is still
      controversial and ambiguous. We performed in this study a more precise estimation
      of the relationship by meta-analyzing the currently available evidence from
      literature. A total of 11 publications containing 12 studies including 10,137
      cases and 15,566 controls were identified. Crude odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of association in the
      codominant model, dominant model, and recessive model. When all the studies were
      pooled into the meta-analysis, there was no evidence showing a significant
      association between -174G > C and breast cancer risk (for CC vs. GG: OR = 1.024,
      95% CI: 0.935-1.121; for GC vs. GG: OR = 1.008, 95% CI: 0.946-1.073; for dominant
      model: OR = 0.980, 95% CI: 0.857-1.121; and for recessive model: OR = 1.027, 95%
      CI: 0.944-1.117). In the subgroup analyses by ethnicity, no significant
      associations were observed in any genetic models. In summary, the present meta
      analysis suggests that the functional polymorphism -174G > C within the IL-6 gene
      promoter is not associated with breast cancer risk. Identifying a unique SNP as a
      breast cancer risk predictor remains a very challenging task.

PMID- 20043206
TI  - Factors influencing the association between CYP17 T34C polymorphism and the risk
      of breast cancer: meta-regression and subgroup analysis.
AB  - A number of studies have been investigated the association between CYP17 T34C
      polymorphism and the risk of breast cancer; the results of these studies are
      inconsistent, however. This fact implies that the effect of CYP17 T34C
      polymorphism on susceptibility to breast cancer may be modified by other risk
      factors. In order to provide a more definitive conclusion, a full meta-analysis
      combining and summarizing 24 studies was first performed. Both traditional method
      and Bayesian approach were applied. Odds ratio was estimated using a dominant
      mode of inheritance after a biological justification for the choice of genetic
      model. The results of homogeneity analysis (H = 1.16, I (2) = 25.4%, and P =
      0.127) suggested the presence of heterogeneity across the studies. Thus, random
      effects models simulated by the DerSimonian-Laird method were employed. The
      capability of a Bayesian approach was highlighted in the estimation of a pooled
      odds ratio and 95% confidence interval. The results of meta-analysis (OR = 1.001,
      CI = 0.832-1.208) suggest no significant association in the combined populations.
      Furthermore, Bayesian meta-regression and subgroup analysis were conducted to
      investigate the sources of heterogeneity. The risk factors evaluated in the study
      were menopausal status, ethnicity, age at menarche, age at first birth, parity,
      use of oral contraceptives, body mass index (BMI), and use of hormone repair
      therapy (HRT). After these population stratifications, there was evidence
      indicating that a possible impact of menopausal status, age at menarche, and BMI
      on the association between CYP17 T34C polymorphism and the risk of breast cancer.

PMID- 20043207
TI  - Detection, expression and quantitation of the biodegradative genes in Antarctic
      microorganisms using PCR.
AB  - In this study, 28 hydrocarbon-degrading bacterial isolates from oil-contaminated
      Antarctic soils were screened for the presence of biodegradative genes such as
      alkane hydroxylase (alks), the ISPalpha subunit of naphthalene dioxygenase
      (ndoB), catechol 2,3-dioxygenase (C23DO) and toluene/biphenyl dioxygenase
      (todC1/bphA1) by using polymerase chain reaction (PCR) methods. All naphthalene
      degrading bacterial isolates exhibited the presence of a 648 bp amplicon that
      shared 97% identity to a known ndoB sequence from Pseudomonas putida. Twenty-two
      out of the twenty-eight isolates screened were positive for one, two or all three
      different regions of the C23DO gene. For alkane hydroxylase, all 6 Rhodococcus
      isolates were PCR-positive for a 194 bp and a 552 bp segment of the alkB gene,
      but exhibited variable results with primers located at different segments of this
      gene. Three Pseudomonas spp. 4/101, 19/1, 30/3 amplified 552 bp segment of alkB.
      Only two Pseudomonas sp. 7/156 and 4/101 amplified a segment of alkB exhibiting
      89-94% nucleotide sequence identity with the existing sequence of alkB in the
      GenBank sequence database. Transcripts of three genes, alkB2, C23DO and ndoB,
      that were amplified by DNA-PCR in three different bacterial isolates also
      exhibited positive amplification by reverse transcriptase PCR (RT-PCR) method
      confirming that these genes are functional. A competitive PCR (cPCR) method was
      developed for a quantitative estimation of ndoB from pure cultures of the
      naphthalene-degrading Pseudomonas sp. 30/2. A minimum of 1 x 10(7) copies of the
      ndoB gene was detected based on the comparison of the intensities of the
      competitor and target DNA bands. It is expected that the identification and
      characterization of the biodegradative genes will provide a better understanding
      of the catabolic pathways in Antarctic psychrotolerant bacteria, and thereby help
      support bioremediation strategies for oil-contaminated Antarctic soils.

PMID- 20043208
TI  - Predictors of follow-up completion among runaway substance-abusing adolescents
      and their primary caretakers.
AB  - Follow-up rates reported among longitudinal studies that focus on runaway
      adolescents and their families are relatively low. Identifying factors associated
      with follow-up completion might be useful for improving follow-up rates and
      therefore study validity. The present study explored how individual- and family
      level constructs, as well as research project activities, influence the follow-up
      completion rate among runaway adolescents (N = 140) and their primary caregiver.
      Results showed that follow-up completion rates decreased as the number of
      research assistants (RA) assigned to each case increased and as participants'
      address changes increased. Additionally, among adolescents, more frequent alcohol
      use was associated with lower follow-up rates. The current findings suggest that
      researchers should (1) design their research so that one RA is assigned to each
      specific case, and (2) adjust their retention strategies to account for the
      differences in follow-up rates based upon the participants' drug of choice and
      residential stability.

PMID- 20043209
TI  - Clinical significance of genotypes and precore/basal core promoter mutations in
      HBV related chronic liver disease patients in North India.
AB  - PURPOSE: Data on genotypes, basal core promoter (BCP) and precore mutants of
      hepatitis B virus and their association with different HBV related liver disease
      have been studied inadequately and are controversial. Thus, the aim of this study
      was to determine the incidence of BCP and precore HBV mutants and their
      relationship with HBV genotype and different stages of HBV related liver disease
      in North Indian patients. METHODS: A total 273 patients with different stages of
      HBV related liver diseases were enrolled. Nested polymerase chain reaction (PCR)
      was used to amplify the BCP/PC regions. RFLP and direct sequencing were performed
      to validate the mutations identified in these regions. HBV genotyping was
      accomplished by multiplex PCR. RESULTS: Genotype D was the predominant genotype
      found in each of the various HBV related liver diseases. The BCP mutation was
      found significantly more often in inactive carriers and compensated cirrhosis as
      compared to the other groups. The BCP mutation was present in 29.1% of patients
      with genotype D versus 17.1% with genotype A (P = 0.001). The precore mutation
      was also more frequently observed with genotype D compared with genotype A (36.9
      vs. 4.8%, P = 0.0007). CONCLUSION: Genotype D is predominant in North Indian
      patients. The BCP and precore mutations occur in one-third of HBV positive
      patients in association with the genotype D. We did not find any correlation with
      severity of liver disease with genotypes and mutations.

PMID- 20043210
TI  - Idiom comprehension in Mandarin-speaking children.
AB  - This study examines the effect of familiarity, context, and linguistic convention
      on idiom comprehension in Mandarin speaking children. Two experiments (a
      comprehension task followed by a comprehension task coupled with a metapragmatic
      task) were administered to test participants in three age groups (6 and 9-year
      olds, and an adult control group). Laval (Journal of Pragmatics 35(2):723-739,
      2003) showed that familiarity had an effect on idiom comprehension for French 9
      year-olds. However, our finding showed that familiarity was important for 6-year
      old Chinese children when a context was not given. Abkarian et al. (Journal of
      Speech and Hearing Research 35:580-587, 1992) claimed that context has little or
      no effect on comprehension for children under 6. Our results show that context
      has an effect on 6-year-old children's understanding of idioms in a different
      way. Overall, our major research findings are: (1) Familiarity first appeared in
      responses at age 6. (2) Context played an important role in idiom comprehension
      and had different effects on different age groups. (3) Linguistic convention
      starts from age 6 on, and a significant effect took place at the age of 9. (4)
      Metapragmatic knowledge showed at the age of 6 and could surface even younger. As
      context and linguistic convention have a substantial effect on the comprehension
      of idioms, it is necessary to take them into account to explain language
      functioning and communicative situations.

PMID- 20043211
TI  - English vowel spaces produced by Japanese speakers: the smaller point vowels' and
      the greater schwas'.
AB  - This study investigated how Japanese-speaking learners of English pronounce the
      three point vowels /i/, /u/, and /a/ appearing in the first and second
      monosyllabic words of English noun phrases, and the schwa /e/ appearing in
      English disyllabic words. First and second formant (F1 and F2) values were
      measured for four Japanese speakers and two American English speakers. The
      hypothesis that the area encompassed by the point vowels in the F1-F2 vowel space
      tends to be smaller for the Japanese speakers than for the English speakers was
      verified. The hypothesis that the area formed by the three schwas in chicke_n,
      spoonfu_l, and Tarza_n is greater for the Japanese speakers than for the English
      speakers and its related hypothesis were largely upheld. Implications for further
      research are briefly discussed.

PMID- 20043213
TI  - On the irreducible individuality of the person and the fullness of life: simon
      gray's smoking diaries.
AB  - This article aims to challenge and expand notions of health, health care and
      health promotion, particularly in relation to smoking, via a consideration of the
      autobiographical literary work of the English playwright, Simon Gray. Gray died
      in 2008, having written a series of reflective autobiographical books, The
      Smoking Diaries. Gray was a lifelong smoker, perpetually trying to give up his
      habit. This article introduces Gray's diaries and their reflections on life,
      death, health care and smoking. It then enquires what can be learned about
      contemporary health care practices and assumptions from Gray's work. Finally, it
      reflects on the limits of views of health and health promotion when considered in
      the light of a fully lived life. In the life under consideration, health care
      risks are very differently understood to those prevalent in the medical
      community. Literary approaches to thinking about smoking are thus seen to place
      health and health care in broader, richer, and less instrumental perspectives
      than those that are common amongst contemporary health professionals and
      institutions.

PMID- 20043212
TI  - Mechanisms of apoptosis in Crustacea: What conditions induce versus suppress cell
      death?
AB  - Arthropoda is the largest of all animal phyla and includes about 90% of extant
      species. Our knowledge about regulation of apoptosis in this phylum is largely
      based on findings for the fruit fly Drosophila melanogaster. Recent work with
      crustaceans shows that apoptotic proteins, and presumably mechanisms of cell
      death regulation, are more diverse in arthropods than appreciated based solely on
      the excellent work with fruit flies. Crustacean homologs exist for many major
      proteins in the apoptotic networks of mammals and D. melanogaster, but
      integration of these proteins into the physiology and pathophysiology of
      crustaceans is far from complete. Whether apoptosis in crustaceans is mainly
      transcriptionally regulated as in D. melanogaster (e.g., RHG 'killer' proteins),
      or rather is controlled by pro- and anti-apoptotic Bcl-2 family proteins as in
      vertebrates needs to be clarified. Some phenomena like the calcium-induced
      opening of the mitochondrial permeability transition pore (MPTP) are apparently
      lacking in crustaceans and may represent a vertebrate invention. We speculate
      that differences in regulation of the intrinsic pathway of crustacean apoptosis
      might represent a prerequisite for some species to survive harsh environmental
      insults. Pro-apoptotic stimuli described for crustaceans include UV radiation,
      environmental toxins, and a diatom-produced chemical that promotes apoptosis in
      offspring of a copepod. Mechanisms that serve to depress apoptosis include the
      inhibition of caspase activity by high potassium in energetically healthy cells,
      alterations in nucleotide abundance during energy-limited states like diapause
      and anoxia, resistance to opening of the calcium-induced MPTP, and viral
      accommodation during persistent viral infection. Characterization of the players,
      pathways, and their significance in the core machinery of crustacean apoptosis is
      revealing new insights for the field of cell death.

PMID- 20043214
TI  - Factors associated with colorectal cancer screening among a low-income,
      multiethnic, highly insured population: does provider's understanding of the
      patient's social context matter?
AB  - The primary aim of this paper was to explore whether provider's understanding of
      patient's social context is associated with screening uptake, independent of
      provider's recommendation. Baseline data were collected in 2004-2005 from a
      cluster randomized control trial in 12 low-income housing sites. Participants
      included 695 low-income, multiethnic adults aged 50 years and over who were
      primarily insured (97%). Provider's recommendation was significantly associated
      with current adherence to colorectal cancer (CRC) screening. Provider's
      understanding of patient's social context, as operationalized by how well
      participants felt that their provider knew (a) their responsibilities at work,
      home, or school; (b) their worries about health; and (c) them as a person and
      their values and beliefs, was also significantly associated with current
      adherence to screening, independent of provider's recommendation. Participants
      who reported that their provider knew them well on two or three items were
      significantly more likely to be current with CRC screening compared to those who
      reported their provider knew them well on only one or none of the items (odds
      ratio = 1.56; 95% confidence interval = 1.06, 2.29). Our findings indicate that
      provider's understanding of patient's social context, independent of provider's
      recommendation for CRC screening, contributed to adherence to CRC screening in
      this low-income, multiethnic population.

PMID- 20043215
TI  - A survey of prognostic value of serum factors in multiple myeloma patients before
      treatment: macrophage-colony stimulating factor (M-CSF) is a powerful predictor
      of survival.
AB  - Cytokines are involved in the pathogenesis of multiple myeloma (MM) and other
      cancers. The aim of this study was to evaluate a range of cytokines of diverse
      activity in patients with multiple myeloma for a possible prognostic value.
      Concentrations of the following cytokines and cytokine receptors were measured by
      ELISA in the sera of 64 untreated MM patients: IL-6, IL-8, IL-10, TNFalpha, sTNF
      R I and II, sIL-2Ralpha, IL-1ra, M-CSF, G-CSF, VEGF, and bFGF. Serum levels of
      sTNF RI, IL-6, and bFGF were elevated in over 50% of patients. There was an
      inverse relationship between sTNF RII, TNFalpha, IL-1ra, and albumin levels.
      There was no significant relationship between cytokines/cytokine receptors and
      other serum correlates of myeloma. In a univariate survival analysis, beta2
      microglobulin, LDH, sIL-2Ralpha, sTNF RI, and M-CSF were significant variables.
      In a multivariate analysis, only M-CSF and beta2-microglobulin retained a
      significant influence on survival. Serum M-CSF may be considered another
      independent and clinically useful prognostic factor in multiple myeloma.

PMID- 20043216
TI  - Experience with sorafenib and the elderly patient.
AB  - Renal cell carcinoma primarily affects older individuals. Approximately half of
      all new renal cell carcinoma diagnoses are made in persons 65 years of age or
      older. Devising a treatment plan for the elderly patient population requires
      special consideration. Age-related physiological, cognitive, and social
      characteristics of elderly patients may influence each stage of patient care.
      Until recently, treatment options were limited for elderly patients with renal
      cell carcinoma. Sorafenib is the first multikinase inhibitor approved for use in
      renal cell carcinoma in the United States and Europe. In the phase III Treatment
      Approaches in Renal Cell Cancer Global Evaluation Trial, sorafenib significantly
      extended progression-free survival in patients with advanced renal cell
      carcinoma, regardless of age. Incidence rates of adverse events were not
      significantly higher in elderly patients receiving sorafenib than in younger
      patients. Thus, sorafenib represents an important treatment option for elderly
      patients with renal cell carcinoma. This report describes particular
      considerations for physicians to be aware of when choosing a treatment regimen
      for their elderly patients with renal cell carcinoma and offers recommendations
      on how to integrate specific management strategies into clinical practice that
      will optimize the use of sorafenib in the elderly. The strategies focus on
      patient selection, assessment of quality of life, management of adverse events,
      and appropriate dose modifications. The goal of these recommendations is to
      maximize the clinical benefit of sorafenib in the elderly patient population
      through appropriate use.

PMID- 20043217
TI  - A new feature of the stress response: increase in endocytosis mediated by Hsp70.
AB  - The expression of heat shock proteins (HSP) is a conserved cellular response to a
      variety of stresses. These proteins have been found to refold denatured
      polypeptides and stabilize critical cellular processes. In this study, we
      introduce a new component of the stress response: the increase of receptor
      mediated uptake of macromolecules from the external environment. We observed that
      endocytosis of transferrin, which is involved in the delivery of iron to the
      cell, was increased after stress induced by heat shock or after incubation with
      inhibitors of Hsp90 function. In both cases, the increase in endocytosis was
      reverted by inhibition of transcription, suggesting that gene expression is
      required. Transfection of cells with Hsp70 gene or inhibition of its expression
      by siRNA confirmed the role of this HSP in the increase of endocytosis. The
      mechanism for the enhancement of transferrin uptake was related to an accelerated
      internalization of the ligand-receptor complex as well as an increase in receptor
      recycling. These observations constitute a new paradigm for the cellular
      protection induced by HSP.

PMID- 20043218
TI  - Ondansetron-induced headache in a parturient mimicking postdural puncture
      headache.

PMID- 20043219
TI  - Best evidence in critical care medicine. Intensive vs conventional blood glucose
      control in critically ill patients.

PMID- 20043220
TI  - Development and validation of a rapid method for the detection of latrunculol A
      in plasma.
AB  - Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin
      inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than
      latrunculin A against both murine and human colon tumor cell lines in vitro.
      Currently, there are no reports regarding the bioavailability of latrunculol A in
      vivo. This study was undertaken as a prelude to pharmacokinetic assessments and
      it is the first work where bioavailability of latrunculol A was studied. In the
      present work, a simple plasma preparation and a rapid HPLC method have been
      developed. Mouse plasma containing latrunculol A was first treated by
      acetonitrile and then centrifuged at 14,000 rpm at 4  degrees C for 25 min. The
      supernatant was injected in an HPLC system comprising a Waters Symmetry NH(2)
      column, a mobile phase of acetonitrile/water (95/5, v/v), a flow rate of 1.0
      mL/min, at 220 nm. The method was validated by parameters including a good linear
      correlation, a limit of quantification of 9 ng/mL, and a good precision with a
      coefficient variation of 1.65, 1.86, and 1.26% for 20, 400, and 800 ng/mL,
      respectively. With this simple method, excellent separation and sensitivity of
      latrunculol A are achieved, thus allowing a rapid analysis of the plasma samples
      for absorption, distribution, and metabolism studies.

PMID- 20043221
TI  - MALDI-TOF MS stability study of model poly(p-phenylene terephthalamide)s.
AB  - In the present study, we address the possibility of matrix-assisted laser
      desorption/ionization (MALDI)-time-of-flight MS analysis-induced chain
      fragmentation in poly(p-phenylene terephthalamide) (PPD-T) by considering two
      possible sources: (1) grinding-induced fragmentation resulting from the
      evaporation-grinding MALDI sample preparation method (E-G method) and (2) in
      source/metastable fragmentation induced by the MALDI laser. An analysis of
      variance (ANOVA) statistical study found, with a high probability, that obtaining
      MALDI spectra with the effective laser area as large as possible (the "fanned
      out" setting) did not cause any chain fragmentation due to the E-G MALDI sample
      preparation method, even when three additional grinding steps were used. However,
      the effect of laser fluence was less clear. A significant effect of laser fluence
      was observed for lower mass oligomers (<1,400 Da), but there was essentially no
      effect for higher mass species up to our limit of ANOVA measurement
      (approximately 2,300 Da). Plausible explanations are presented to explain these
      observations. The most likely scenario is that "unexpected" end-group
      modifications occur during PPD-T synthesis, producing small quantities of low
      mass species, which are amplified by the MALDI-EG extraction procedure.

PMID- 20043222
TI  - Clinical and immunological responses in metastatic melanoma patients vaccinated
      with a high-dose poly-epitope vaccine.
AB  - BACKGROUND: Safety and cellular immunogenicity of rising doses and varying
      regimens of a poly-epitope vaccine were evaluated in advanced metastatic
      melanoma. The vaccine comprised plasmid DNA and recombinant modified vaccinia
      virus Ankara (MVA) both expressing a string (Mel3) of seven HLA.A2/A1 epitopes
      from five melanoma antigens. METHODS: Forty-one HLA-A2 positive patients with
      stage III/IV melanoma were enrolled. Patient groups received one or two doses of
      DNA.Mel3 followed by escalating doses of MVA.Mel3. Immunisations then continued
      eight weekly in the absence of disease progression. Epitope-specific CD8+ T cell
      responses were evaluated using ex-vivo tetramer and IFN-gamma ELISPOT assays.
      Safety and clinical responses were monitored. RESULTS: Prime-boost DNA/MVA
      induced Melan-A-specific CD8+ T cell responses in 22/31 (71%) patients detected
      by tetramer assay. ELISPOT detected a response to at least one epitope in 10/31
      (32%) patients. T cell responder rates were <50% with low-dose DNA/MVA, or MVA
      alone, rising to 91% with high-dose DNA/MVA. Among eight patients showing
      evidence of clinical benefit-one PR (24 months+), five SD (5 months+) and two
      mixed responses-seven had associated immune responses. Melan-A-tetramer+ immunity
      was associated with a median 8-week increase in time-to-progression (P = 0.037)
      and 71 week increase in survival (P = 0.0002) compared to non-immunity. High-dose
      vaccine was well tolerated. The only significant toxicities were flu-like
      symptoms and injection-site reactions. CONCLUSIONS: DNA.Mel3 and MVA.Mel3 in a
      prime-boost protocol generated high rates of immune response to melanoma antigen
      epitopes. The treatment was well tolerated and the correlation of immune
      responses with patient outcomes encourages further investigation.

PMID- 20043223
TI  - Circulating tumour-derived microvesicles in plasma of gastric cancer patients.
AB  - Cell membrane microfragments called microvesicles (MV) originating from different
      cells are circulating in the blood of healthy subjects and their elevated numbers
      are found in different diseases, including cancer. This study was designed to
      characterise MV present in plasma of gastric cancer patients. Since majority of
      MV in blood are platelets-derived (PMV), plasma samples deprived of PMV were
      used. In comparison to control, the number of MV in patients was significantly
      elevated in all stages, higher in more advanced disease. Patients' MV showed an
      increased membrane expression of CCR6 and HER-2/neu. The proportion of MV
      carrying some leucocyte determinants was low and similar in patients and control.
      Transmission electron microscopy showed their substantial heterogeneity in size
      and shape. The size determined by dynamic light scattering analysis confirmed
      this heterogeneity. The MV size distribution in patients was broader within the
      range of 10-800 nm, while in control MV showed 3-mode distribution within the
      range of 10-400 nm. Atomic force microscopy confirmed MV size heterogeneity with
      implication that larger objects represented aggregates of smaller microparticles.
      Patients' MV exhibited increased absolute values of zeta potential, indicating a
      higher surface charge. Tumour markers HER-2/neu, MAGE-1, c-MET and EMMPRIN were
      detected both in control and patients' samples with stronger expression in the
      latter. Significantly higher expression of MAGE-1 and HER-2/neu mRNA was observed
      in individual patients. All together, it suggests that at least some MV in plasma
      of gastric cancer patients are tumour-derived. However, their role in cancer
      requires further studies.

PMID- 20043224
TI  - Successful intra-arterial chemotherapy for extramammary Paget's disease of the
      axilla in a patient with Parkinson's disease.
AB  - Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm occurring
      less frequently in men and even more rarely in the axilla. A 59-year-old man with
      severe Parkinson's disease presented with axillary EMPD. The neurological
      comorbidity made treatment of the EMPD problematical and prompted us to propose
      locoregional intra-arterial chemotherapy in single short sessions. Two innovative
      chemotherapeutic macrocomplexes were used: doxorubicin incorporated in large
      liposomes and the taxane paclitaxel incorporated in albumin nanoparticles. A
      therapeutic response was seen right from the first treatment and was
      macroscopically close to complete after four cycles. Five months after the end of
      treatment the patient had minimal visible disease and had enjoyed a distinct
      improvement in quality of life, with no noteworthy complications related to the
      intra-arterial chemotherapy with percutaneous transfemoral catheterization.

PMID- 20043225
TI  - AoxA is a major peroxisomal long chain fatty acyl-CoA oxidase required for beta
      oxidation in A. nidulans.
AB  - Filamentous fungi can use a variety of fatty acids (FA) as sole carbon and energy
      sources. Aspergillus nidulans has been shown to possess both peroxisomal and
      mitochondrial beta-oxidation pathways. In these studies, the major peroxisomal
      long chain fatty acyl coenzyme A oxidase AoxA was identified. AoxA was shown to
      be localised to peroxisomes and deletion of the aoxA gene leads to reduced growth
      on long chain FA, but not on short chain FA. AoxA is predicted to be part of the
      same peroxisomal beta-oxidation pathway as the bifunctional protein FoxA. In
      addition, an aoxA(p)lacZ reporter gene construct is induced by short and long
      chain FA and the induction is dependent on the transcriptional regulators FarA,
      FarB and ScfA with FarA being required for the induction by short chain as well
      as long chain FA and FarB and ScfA being required for induction of aoxA by short
      chain FA. It is proposed that there are additional peroxisomal beta-oxidation
      pathways in A. nidulans, which include fatty acyl-CoA dehydrogenases with a
      partially overlapping substrate range and include a pathway for short chain FA.

PMID- 20043226
TI  - Genomic analysis of severe hypersensitivity to hygromycin B reveals linkage to
      vacuolar defects and new vacuolar gene functions in Saccharomyces cerevisiae.
AB  - The vacuole of Saccharomyces cerevisiae has been a seminal model for studies of
      lysosomal trafficking, biogenesis, and function. Several yeast mutants defective
      in such vacuolar events have been unable to grow at low levels of hygromycin B,
      an aminoglycoside antibiotic. We hypothesized that such severe hypersensitivity
      to hygromycin B (hhy) is linked to vacuolar defects and performed a genomic
      screen for the phenotype using a haploid deletion strain library of non-essential
      genes. Fourteen HHY genes were initially identified and were subjected to
      bioinformatics analyses. The uncovered hhy mutants were experimentally
      characterized with respect to vesicular trafficking, vacuole morphology, and
      growth under various stress and drug conditions. The combination of
      bioinformatics analyses and phenotypic characterizations implicate defects in
      vesicular trafficking, vacuole fusion/fission, or vacuole function in all hhy
      mutants. The collection was enriched for sensitivity to monensin, indicative of
      vacuolar trafficking defects. Additionally, all hhy mutants showed severe
      sensitivities to rapamycin and caffeine, suggestive of TOR kinase pathway
      defects. Our experimental results also establish a new role in vacuolar and
      vesicular functions for two genes: PAF1, encoding a RNAP II-associated protein
      required for expression of cell cycle-regulated genes, and TPD3, encoding the
      regulatory subunit of protein phosphatase 2A. Thus, our results support linkage
      between severe hypersensitivity to hygromycin B and vacuolar defects.

PMID- 20043227
TI  - The carboxy-terminal fragment of alpha(1A) calcium channel preferentially
      aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje
      cells.
AB  - Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative
      disease caused by a small polyglutamine (polyQ) expansion (control: 4-20Q; SCA6:
      20-33Q) in the carboxyl(C)-terminal cytoplasmic domain of the alpha(1A) voltage
      dependent calcium channel (Ca(v)2.1). Although a 75-85-kDa Ca(v)2.1 C-terminal
      fragment (CTF) is toxic in cultured cells, its existence in human brains and its
      role in SCA6 pathogenesis remains unknown. Here, we investigated whether the
      small polyQ expansion alters the expression pattern and intracellular
      distribution of Ca(v)2.1 in human SCA6 brains. New antibodies against the
      Ca(v)2.1 C-terminus were used in immunoblotting and immunohistochemistry. In the
      cerebella of six control individuals, the CTF was detected in sucrose- and SDS
      soluble cytosolic fractions; in the cerebella of two SCA6 patients, it was
      additionally detected in SDS-insoluble cytosolic and sucrose-soluble nuclear
      fractions. In contrast, however, the CTF was not detected either in the nuclear
      fraction or in the SDS-insoluble cytosolic fraction of SCA6 extracerebellar
      tissues, indicating that the CTF being insoluble in the cytoplasm or mislocalized
      to the nucleus only in the SCA6 cerebellum. Immunohistochemistry revealed
      abundant aggregates in cell bodies and dendrites of SCA6 Purkinje cells (seven
      patients) but not in controls (n = 6). Recombinant CTF with a small polyQ
      expansion (rCTF-Q28) aggregated in cultured PC12 cells, but neither rCTF-Q13
      (normal-length polyQ) nor full-length Ca(v)2.1 with Q28 did. We conclude that
      SCA6 pathogenesis may be associated with the CTF, normally found in the
      cytoplasm, being aggregated in the cytoplasm and additionally distributed in the
      nucleus.

PMID- 20043228
TI  - Evaluation of the Oxycon Mobile metabolic system against the Douglas bag method.
AB  - The aim of this study was to evaluate two versions of the Oxycon Mobile portable
      metabolic system (OMPS1 and OMPS2) in a wide range of oxygen uptake, using the
      Douglas bag method (DBM) as criterion method. The metabolic variables VO2, VCO2
      respiratory exchange ratio and VE were measured during submaximal and maximal
      cycle ergometer exercise with sedentary, moderately trained individuals and
      athletes as participants. Test-retest reliability was investigated using the
      OMPS1. The coefficients of variation varied between 2 and 7% for the metabolic
      parameters measured at different work rates and resembled those obtained with the
      DBM. With the OMPS1, systematic errors were found in the determination of VO2 and
      VCO2 At submaximal work rates VO2 was 6-14% and VCO2 5-9% higher than with the
      DBM. At VO2(max) both VO2 and VCO2 were slightly lower as compared to DBM (-4.1
      and -2.8% respectively). With OMPS2, VO2 was determined accurately within a wide
      measurement range (about 1-5.5 L min(-1)), while VCO2 was overestimated (3-7%).
      VE was accurate at submaximal work rates with both OMPS1 and OMPS2, whereas
      underestimations (4-8%) were noted at VO2(max). The present study is the first to
      demonstrate that a wide range of VO2 can be measured accurately with the Oxycon
      Mobile portable metabolic system (second generation). Future investigations are
      suggested to clarify reasons for the small errors noted for VE and VCO2 versus
      the Douglas bag measurements, and also to gain knowledge of the performance of
      the device under applied and non-laboratory conditions.

PMID- 20043229
TI  - Single-nucleotide polymorphisms in vascular Ca2+-activated K+-channel genes and
      cardiovascular disease.
AB  - In the cardiovascular system, Ca2+-activated K+-channels (KCa) are considered
      crucial mediators in the control of vascular tone and blood pressure by
      modulating the membrane potential and shaping Ca2+-dependent contraction.
      Vascular smooth muscle cells express the BKCa channel which fine-tunes
      contractility by providing a negative feedback on Ca2+-elevations. BKCa channel's
      ion-conducting alpha-subunit is encoded by the KCa1.1 gene, and the accessory and
      Ca2+-sensitivity modulating beta1-subunit is encoded by the KCNMB1 gene. Vascular
      endothelial cells express the calmodulin-gated KCa channels IKCa (encoded by the
      KCa3.1 gene) and SKCa (encoded by the KCa2.3 gene). These two channels mediate
      endothelial hyperpolarization and initiate the endothelium-derived
      hyperpolarizing factor-dilator response. Considering these essential roles of KCa
      in arterial function, mutations in KCa genes have been suspected to contribute to
      cardiovascular disease in humans. So far, DNA sequence analysis in the population
      and patient cohorts has identified single-nucleotide polymorphisms (SNPs) in the
      BKCa beta1-subunit gene as well as in the alpha-subunit gene (KCa1.1). Some of
      these SNPs produce amino acid exchanges and evoke alterations of channel
      functions ("gain-of-function" as well as "loss-of-function"). Moreover, the
      epidemiological studies showed that the presence of the E65K polymorphism in,
      e.g., BKCa beta1-subunit gene (producing a "gain-of-function") lowers the
      prevalence for severe hypertension and myocardial infarction. Other SNPs in the
      BKCa alpha-subunit gene and also in the KCa3.1 gene expressed in the endothelium
      have been suggested to increase the risk of cardiovascular disease. These
      findings from sequence analysis of human KCa genes, and epidemiological studies
      thus provide evidence that genetic variations and mutations in KCa channel genes
      contribute to human cardiovascular disease.

PMID- 20043231
TI  - The chemically synthesized human relaxin-2 analog, B-R13/17K H2, is an RXFP1
      antagonist.
AB  - Relaxin is a pleiotropic hormone which exerts its biological functions through
      its G-protein coupled receptor, RXFP1. While relaxin is well known for its
      reproductive and antifibrotic roles, recent studies suggest that it is produced
      by cancer cells and acts on RXFP1 to induce growth and metastasis. Furthermore,
      more recently Silvertown et al. demonstrated that lentiviral production of a
      human gene-2 (H2) relaxin analog reduced the growth of prostate xenograft tumors.
      The authors proposed that the lentivirally produced peptide was an RXFP1
      antagonist; however, the processed form of the peptide produced was not
      demonstrated. In this study, we have chemically synthesized the H2 relaxin
      analog, B-R13/17K H2 relaxin, and subjected it to detailed chemical
      characterization by HPLC, MALDI-TOF mass spectrometry, and amino acid analysis.
      The biological activity of the synthetic peptide was then tested in three
      different cell lines. It was found to bind with 500-fold lower affinity than H2
      relaxin to RXFP1 receptors over-expressed in HEK-293T cells where it acted as a
      partial agonist. However, in cells which natively express the RXFP1 receptor, rat
      renal myofibroblasts and MCF-7 cancer cells, it acted as a full antagonist.
      Importantly, it was able to significantly inhibit cell invasion induced by H2
      relaxin in MCF-7 cells consistent with the results of the lentiviral-driven
      expression in prostate cancer cells. The relaxin analog, B-R13/17K H2, can now be
      used as a tool to further understand RXFP1 function, and serve as a template for
      drug design for a therapeutic to treat prostate and other cancers.

PMID- 20043230
TI  - Molecular evolution of SPARC: absence of the acidic module and expression in the
      endoderm of the starlet sea anemone, Nematostella vectensis.
AB  - The matricellular glycoprotein SPARC is composed of three functional domains that
      are evolutionarily conserved in organisms ranging from nematodes to mammals: a
      Ca(2+)-binding glutamic acid-rich acidic domain at the N-terminus (domain I), a
      follistatin-like module (domain II), and an extracellular Ca(2+)-binding (EC)
      module that contains two EF-hands and two collagen-binding epitopes (domain III).
      We report that four SPARC orthologs (designated nvSPARC1-4) are expressed by the
      genome of the starlet anemone Nematostella vectensis, a diploblastic basal
      cnidarian composed of an ectoderm and endoderm separated by collagen-based
      mesoglea. We also report that domain I is absent from all N. vectensis SPARC
      orthologs. In situ hybridization data indicate that N. vectensis SPARC mRNAs are
      restricted to the endoderm during post-gastrula development. The absence of the
      Ca(2+)-binding N-terminal domain in cnidarians and conservation of collagen
      binding epitopes suggests that SPARC first evolved as a collagen-binding
      matricellular glycoprotein, an interaction likely to be dependent on the binding
      of Ca(2+)-ions to the two EF-hands in the EC domain. We propose that further
      Ca(2+)-dependent activities emerged with the acquisition of an acidic N-terminal
      module in triplobastic organisms.

PMID- 20043232
TI  - Protective effects of emodin combined with danshensu on experimental severe acute
      pancreatitis.
AB  - OBJECTIVE AND DESIGN: In the present experiment, we aimed to determine the
      feasibility and curative effects of emodin combined with danshensu on
      experimental severe acute pancreatitis (SAP) and the mutual benefit of this
      synergistic strategy by a prospective animal study. MATERIAL: Eighty Wistar rats
      were randomly divided into four groups (n = 20). TREATMENT: SAP was elicited by a
      retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct.
      SAP rats in each group received no further intervention, emodin alone, danshensu
      (DSS) alone, and emodin combined with DSS (EDSS), respectively. METHODS: 48 h
      after SAP induction, all surviving animals were sacrificed to collect blood and
      tissue samples for the following measurements: serum levels of amylase, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D
      lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA),
      myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation
      as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified
      and the severity of pancreatic damage was analyzed by pathological grading and
      scoring. RESULTS: Compared with the SAP group, the emodin, DSS and EDSS groups
      had significant differences in every index. Furthermore, EDSS obviously improved
      all the parameters mentioned above so as to counteract inflammatory response and
      oxidative stress, as well as most effectively abating pancreatic and intestinal
      barrier injury. CONCLUSIONS: EDSS exerted protective effects on SAP rats and
      remarkably alleviated the severity of experimental SAP. Mechanisms that might
      account for the beneficial effects include protecting the intestinal barrier,
      inhibiting over-inflammatory reaction and abating oxidative stress. The combined
      strategy proved to be more effective than either emodin or DSS alone and may
      cause synergistic effects in combination in the early stage of SAP. Broad
      potential for future clinical practice is foreseeable.

PMID- 20043233
TI  - A composite transcriptional signature differentiates responses towards closely
      related herbicides in Arabidopsis thaliana and Brassica napus.
AB  - In this study, genome-wide expression profiling based on Affymetrix ATH1 arrays
      was used to identify discriminating responses of Arabidopsis thaliana to five
      herbicides, which contain active ingredients targeting two different branches of
      amino acid biosynthesis. One herbicide contained glyphosate, which targets 5
      enolpyruvylshikimate-3-phosphate synthase (EPSPS), while the other four
      herbicides contain different acetolactate synthase (ALS) inhibiting compounds. In
      contrast to the herbicide containing glyphosate, which affected only a few
      transcripts, many effects of the ALS inhibiting herbicides were revealed based on
      transcriptional changes related to ribosome biogenesis and translation, secondary
      metabolism, cell wall modification and growth. The expression pattern of a set of
      101 genes provided a specific, composite signature that was distinct from other
      major stress responses and differentiated among herbicides targeting the same
      enzyme (ALS) or containing the same chemical class of active ingredient
      (sulfonylurea). A set of homologous genes could be identified in Brassica napus
      that exhibited a similar expression pattern and correctly distinguished exposure
      to the five herbicides. Our results show the ability of a limited number of genes
      to classify and differentiate responses to closely related herbicides in A.
      thaliana and B. napus and the transferability of a complex transcriptional
      signature across species.

PMID- 20043234
TI  - Involvement of auxin signaling mediated by IAA14 and ARF7/19 in membrane lipid
      remodeling during phosphate starvation.
AB  - In higher plants, phosphate (Pi) deficiency induces the replacement of
      phospholipids with the nonphosphorous glycolipids digalactosyldiacylglycerol
      (DGDG) and sulfoquinovosyldiacylglycerol (SQDG). Genes involved in membrane lipid
      remodeling are coactivated in response to Pi starvation, but the mechanisms that
      guide this response are largely unknown. Previously, we reported the importance
      of auxin transport for DGDG accumulation during Pi starvation. To understand the
      role of auxin signaling in Arabidopsis membrane lipid remodeling, we analyzed slr
      1, a gain-of-function mutant of IAA14 (a repressor of auxin signaling), and
      arf7arf19, a loss-of-function mutant of auxin response factors ARF7 and ARF19. In
      slr-1 and arf7arf19, Pi stress-induced accumulation of DGDG and SQDG was
      suppressed. Reduced upregulation of glycolipid synthase and phospholipase genes
      in these mutants under Pi-deficient conditions indicates that IAA14 and ARF7/19
      affect membrane lipid remodeling at the level of transcription. Pi stress
      dependent induction of a non-protein-coding gene, IPS1, was also lower in slr-1
      and arf7arf19, whereas expression of At4 (another Pi stress-inducible non-protein
      coding gene), anthocyanin accumulation, and phosphodiesterase induction were not
      reduced in the shoot. High free Pi content was observed in slr-1 and arf7arf19
      even under Pi-deficient conditions, suggesting that Pi homeostasis during Pi
      starvation is altered in these mutants. These results demonstrate a requirement
      of auxin signaling mediated by IAA14 and ARF7/19 for low-Pi adaptation in
      Arabidopsis.

PMID- 20043235
TI  - In situ expression of ribosomal protein L21 in developing tooth germ of the mouse
      lower first molar.
AB  - We previously performed cDNA subtraction between the mouse mandibles at embryonic
      day 10.5 (E10.5) in the pre-initiation stage of the odontogenesis and E12.0 in
      the late initiation stage to investigate the key regulator genes in
      odontogenesis. Ribosomal protein L21 (Rpl21) is one of differentially expressed
      genes in the E12.0 mandible. This study examined the precise expression pattern
      of Rpl21 mRNA in the mouse mandibular first molar by in situ hybridization. Rpl21
      mRNA was expressed in the presumptive dental epithelium and the underlying
      mesenchyme at E10.5, and in the thickened dental epithelium at E12.0. Strong in
      situ signals were observed in the epithelial bud at E14.0, and in the enamel
      organ at E15.0. However, either no (E14.0) or only a weak (E15.0) in situ signal
      was found in the primary enamel knot at these gestational days. Rpl21 was
      strongly expressed in the inner enamel epithelium, cervical loop and dental
      lamina from E16.0 to E18.0. In addition, Rpl21 mRNA was also demonstrated in
      various developing cranio-facial organs. These results suggest that Rpl21
      participates in the synthesis of various polypeptides which might be related to
      the initiation and the development of such tooth germ, and also in the synthesis
      of enamel components in the presecretory stage of the ameloblast. Rpl21 for
      protein synthesis might also be related to the morphogenesis of the developing
      cranio-facial organs.

PMID- 20043236
TI  - Astrocytes express Mxi2, a splice isoform of p38MAPK.
AB  - Mitogen-activated protein kinases (MAPKs) are a superfamily of cytoplasmic
      serine/threonine kinases that transduce many types of extracellular stimuli into
      cellular responses. p38MAPK is a member of this family with its active form in a
      diphosphorylated state (p38MAPKdiP). Two strong anti-p38MAPKdiP immunoreactive
      bands (apparent molecular weight 38 and 34 kDa) were detected by Western blotting
      in cultured astrocytes. Using a specific antibody and employing
      immunoprecipitation procedures and SELDI-TOF analysis, the 34 kDa band was found
      to correspond to Mxi2, a splice variant of p38MAPK; cultured astrocytes therefore
      express Mxi2. Separate protein extractions of different subcellular fractions,
      and fluorescent immunovisualisation employing confocal microscopy, showed Mxi2 to
      have a non-nuclear, cytosolic distribution in the studied cells. ERK1/2, protein
      whose intracellular distribution is influenced by Mxi2, showed the same
      cytoplasmic pattern than Mxi2.

PMID- 20043237
TI  - Morphological damages of a glyphosate-treated human keratinocyte cell line
      revealed by a micro- to nanoscale microscopic investigation.
AB  - Among the molecules to which the human skin is exposed, glyphosate is used as an
      herbicide. Glyphosate has been shown to induce in vitro cutaneous cytotoxic
      effects, concomitant with oxidative disorders. In this following study, we
      focused on dynamic events of the loss of HaCaT cell integrity appearing after a
      glyphosate treatment. In these conditions, we showed that glyphosate is able to
      disrupt HaCaT cells and to induce intracellular oxidative cascade. In this aim,
      we optimized the conditions of cell treatment playing on exposure time (from 24 h
      to 30 min), which directly modify the cell viability profile (glyphosate 50%
      inhibition concentration from 28 to 53 mM) and allow to track cells along the
      treatment as an "induction and visualization" process. The combination of atomic
      force and fluorescence microscopic approaches offered opportunities to lead in
      parallel an investigation of the membrane surface and of the intracellular
      disorders, through cytoskeleton, nuclear, and oxidative stress marker targeting.
      The originality of our approach relies on monitoring all events derived from
      oxidative stress in process and performed by simultaneous cytotoxic induction and
      nanoscale cell visualization. We revealed a transition from spread and globular
      to elongated cell morphology, with a drastic cell size reduction, after a dose-
      and time-dependent glyphosate treatment; a redistribution of cell surface
      protrusions was also pointed out. All these membrane damages, added to
      observations of disorganized cytoskeleton, condensed chromatin, and
      overproduction of oxidative reactive species, lead us to conclude that glyphosate
      acts in induction of apoptotic process.

PMID- 20043238
TI  - Integrating TMS with EEG: How and what for?

PMID- 20043239
TI  - TDP-43 dimerizes in human cells in culture.
AB  - TAR DNA-binding protein-43 (TDP-43) is a 43-kDa nuclear protein involved in
      regulation of gene expression. Abnormally, phosphorylated, ubiquitinated, and
      aggregated TDP-43 constitute a principal component of neuronal and glial
      cytoplasmic and nuclear inclusions in the brains of frontotemporal lobar
      degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral
      sclerosis (ALS), although the molecular mechanism that triggers aggregate
      formation remains unknown. By Western blot analysis using anti-TDP-43 antibodies,
      we identified a band with an apparent molecular mass of 86-kDa in HEK293, HeLa,
      and SK-N-SH cells in culture. It was labeled with both N-terminal-specific and C
      terminal-specific TDP-43 antibodies, enriched in the cytosolic fraction, and the
      expression levels were reduced by TDP-43 siRNA but unaltered by treatment with MG
      132 or by expression of ubiqulin-1 or casein kinase-1. By immunoprecipitation
      analysis, we found the interaction between the endogenous full-length TDP-43 and
      the exogenous Flag-tagged TDP-43, and identified the N-terminal half of TDP-43
      spanning amino acid residues 3-183 as an intermolecular interaction domain. When
      the tagged 86-kDa tandemly connected dimer of TDP-43 was overexpressed in HEK293,
      it was sequestered in the cytoplasm and promoted an accumulation of high
      molecular-mass TDP-43-immunoreactive proteins. Furthermore, the 86-kDa band was
      identified in the immunoblot of human brain tissues, including those of ALS.
      These results suggest that the 86-kDa band represents dimerized TDP-43 expressed
      constitutively in normal cells under physiological conditions.

PMID- 20043240
TI  - Effect of jaggery on the quality and intake levels of maize silage.
AB  - Silage, which is anaerobically fermented green fodder, is valued throughout the
      world as a source of animal feed during lean months. Several farms in India use
      carbohydrate sources like jaggery or molasses at 2% for preparation of silage,
      and this increases cost of production. The present study was undertaken to assess
      the effect of jaggery on quality and intake of maize silage, with an objective to
      find out whether additional carbohydrate source is essential in preparation of
      silage using green maize. Three silage types, one without jaggery (A), the second
      with 1% jaggery (B), and the third with 2% jaggery (C) were prepared in
      cylindrical bins under similar conditions. They were compared for colour, pH,
      lactic acid bacteria count, lactic acid content, proximate composition and silage
      intake by sheep. Silage type C with 2% jaggery was significantly different from
      the other two types with values of 3.98 and 805.66 g for pH and mean silage
      intake, respectively. Even though the values of pH and dry matter intake for all
      three silage types were within normal levels, silage type C was significantly
      superior in terms of fermentation and palatability. The method of preparation
      followed could be ideal for small holder farmers requiring less quantity of
      silage.

PMID- 20043241
TI  - "It's just routine." A qualitative study of medicine-taking amongst older people
      in New Zealand.
AB  - AIM: To explore how New Zealanders aged 65 years and older manage their medicines
      in their own homes, and determine the problems and concerns they might have with
      taking them. SETTING: Urban setting, Dunedin (population 120,000), New Zealand.
      METHODS: Twenty in-depth semi-structured interviews were undertaken of community
      dwelling people 65 years and older. Sixty people, from a random sample of 80 from
      the electoral roll, met the recruitment criteria and were invited to participate.
      The first ten men and ten women agreeing to participate were interviewed.
      Interviews were taped and transcribed verbatim. Transcriptions were thematically
      coded and analysed using grounded theory and constant comparison. MAIN OUTCOME
      MEASURES: Emerging themes were explored under the topics: accessing medicines,
      remembering to take medicines, following instructions, practical problems,
      adverse effects, concerns about medicines, and beliefs about medicines. RESULTS:
      Ten of thirteen men and 10/20 women contacted (61%) agreed to participate. The
      men were aged 71, 67-82 years (median, range) and women 77, 69-87 years. They
      were using 140 prescription medicines (median 7, range 3-16) and 34 non
      prescription medicines (1, 0-6); mainly for the nervous system (28%), or the
      cardiovascular system (22%). Participants felt that they had good access to
      medicines, could afford them, managed them well, and had systems and routines to
      help them remember to take them. Occasional doses were missed following a change
      in routine. Practical problems were found such as difficulty swallowing or
      halving tablets. Three-quarters of participants had experienced adverse effects
      during their lives. These were managed by dose or drug changes or by taking
      practical measures. People were worried about adverse effects occurring whether
      or not they had experienced them previously. Beliefs about medicines were mainly
      positive, although some people disliked taking them. CONCLUSION: The people 65
      years and over in this study felt that they could access, afford and manage their
      medicines well. Although many participants had experienced adverse effects, their
      beliefs about medicines were mainly positive. Practical problems and concerns
      should be routinely inquired about and addressed, and prescribing and monitoring
      optimised to minimise adverse effects, in order to assist older people take their
      medicines.

PMID- 20043242
TI  - Is size really all that matters? Remarks on size and necrotic core content of
      atherosclerotic plaques.

PMID- 20043243
TI  - Alterations in intracellular calcium ion concentrations in cerebellar granule
      cells of the CACNA1A mutant mouse, leaner, during postnatal development.
AB  - Maintaining calcium ion (Ca2+) homeostasis is crucial for normal neuronal
      function. Altered Ca2+ homeostasis interferes with Ca2+ signaling processes and
      affects neuronal survival. In this study, we used homozygous leaner and tottering
      mutant mice, which carry autosomal recessive mutations in the gene coding for the
      alpha(1A) pore forming subunit of Ca(V)2.1 (P/Q-type) voltage-gated calcium
      channels (VGCC). Leaner mice show severe ataxia and epilepsy, while tottering
      mice are less severely affected. Leaner cerebellar granule cells (CGC) show
      extensive apoptotic cell death that peaks at postnatal (P) day 20 and continues
      into adulthood. Intracellular Ca2+ ([Ca2+](i)) concentrations in leaner and
      tottering mouse Purkinje cells have been described, but [Ca2+](i) concentrations
      have not been reported for granule cells, the largest neuronal population of the
      cerebellum. Using the ratiometric dye, Fura-2 AM, we investigated the role of
      Ca2+ homeostasis in CGC death during postnatal development by demonstrating basal
      [Ca2+](i), depolarization induced Ca2+ transients, and Ca2+ transients after
      completely blocking Ca(V)2.1 VGCC. From P20 onward, basal [Ca2+](i) levels in
      leaner CGC were significantly lower compared to age-matched wild-type CGC. We
      also compared basal [Ca2+](i) levels in leaner and wild-type CGC to basal
      [Ca2+](i) in tottering CGC. Potassium chloride induced depolarization revealed no
      significant difference in Ca2+ transients between leaner and wild-type CGC,
      indicating that even though leaner CGC have dysfunctional P/Q-type VGCC, Ca2+
      transients after depolarization are the same. This suggests that other VGCC are
      compensating for the dysfunctional P/Q channels. This finding was further
      confirmed by completely blocking Ca(V)2.1 VGCC using omega-Agatoxin IV-A.

PMID- 20043245
TI  - A computer device to deliver behavioral interventions for insomnia.
AB  - An automated program for delivering stimulus control and sleep restriction
      strategies was developed and implemented on a handheld computer and compared to a
      self-help manual program in 90 chronic primary insomnia participants at 6 and 12
      weeks. The computerized program was generally well accepted and utilized. No
      significant differences between conditions were found on questionnaire and sleep
      diary measures, but subsequent exploratory analyses revealed greater percentages
      of participants in the computer condition compared to the self-help condition who
      were classified as without clinically significant insomnia at 6 weeks based on
      Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) criteria.
      Further research is needed on the efficacy of computerized behavioral approaches
      for insomnia, but the results of this study indicate that computerized delivery
      of stimulus control and sleep restriction is feasible and sufficiently promising
      to warrant further study.

PMID- 20043246
TI  - A comparison of actigraphy and parental report of sleep habits in typically
      developing children aged 6 to 11 years.
AB  - There are limited published data comparing the information provided by parental
      reports of sleep habits with actigraphic information. This study compares
      parental report of sleep habits using the Children's Sleep Habits Questionnaire
      with actigraphic data in 91 typically developing children aged 6 to 11 years. The
      study found that sleep duration (as measured using actigraphy [ACT]) was longer
      in children whose parents rated their child as having enough sleep. Parental
      reports of night wakings did not correspond with ACT measures of night wakings.
      The findings show that ACT and parental reports provide differing, but
      complimentary, information about a child's sleep habits.

PMID- 20043247
TI  - Cognitive-behavioral factors associated with sleep quality in chronic pain
      patients.
AB  - People with chronic pain commonly complain of sleep disturbance. This study
      reports the characteristics of the pain and sleep of a large sample of patients
      with chronic pain (n = 160). This study compared subgroups of good sleepers with
      pain (n = 48) and poor sleepers with pain (n = 108). Poor sleepers with pain were
      younger and reported more pain, pain-related disability, depression, pain-related
      anxiety, and dysfunctional beliefs about sleep. Using simultaneous regression
      analysis, this study examined the roles of pain, dysfunctional beliefs about
      sleep, pain-related disability, depression, and pain-related anxiety in
      predicting concurrent sleep quality. The findings are relevant to the development
      of models of sleep disturbance comorbid with chronic pain.

PMID- 20043248
TI  - Effects of two types of ambient sound during sleep.
AB  - This field study investigated whether either of two ambient sounds would improve
      objective sleep (via actigraphy), subjective sleep report, or morning psychomotor
      performance among 28 adults with self-described disturbed sleep. Nights 1 and 4
      were soundless baseline and washout, respectively. On Nights 2 and 3 and 5 and 6,
      participants listened to double-blind counterbalanced paired nights of novel
      Sound A and a commercially available Sound B. Compared to baseline and washout,
      participants reported fewer awakenings during both Sound A and Sound B;
      actigraphically measured sleep was affected by Sound B but not Sound A.
      "Improvements" in sleep during the second exposure night probably reflect an
      increase in homeostatic sleep drive from sleep disturbance on the first exposure
      night. Differences between sounds were accounted for by user volume settings.
      Neither sound led to differences in psychomotor performance.

PMID- 20043250
TI  - Confabulation and delusion: a common monitoring framework.
AB  - Confabulations and delusions both involve the production of false claims.
      Although they may have different types of content, they share several
      characteristics. For example, they are often held with considerable conviction
      and are resistant to counter evidence, they may be acted upon, and they may be
      accompanied by a lack of concern about the false claim or its implications.
      Confabulations and delusions may initially arise from failures in different
      systems (e.g., mnemonic vs. perceptual or affective). However, their shared
      characteristics raise the possibility that the monitoring deficits involved might
      be the same, resulting in failure to reject the confabulatory or delusional
      ideas. In this paper we will focus on the nature of these common monitoring
      deficits. Critically, we argue that monitoring in confabulation and delusion
      involves both unconscious and conscious processes. We propose that an unconscious
      process is responsible for tagging suspect content which needs to be checked for
      veracity by a separate set of conscious evaluative processes. Failure of these
      monitoring processes would allow ideas which ought to be checked and rejected to
      instead be uncritically accepted: This would result in the production of
      confabulations or delusions. Importantly, inclusion of both unconscious and
      conscious monitoring stages allows the model to account for both "endorsement"
      and "explanation" delusions, and both "primary" and "secondary" confabulations.
      Our hope is that this model may provide a theoretical framework to guide
      empirical investigation of the commonalities and differences between the
      conditions.

PMID- 20043249
TI  - Restless legs syndrome risk factors, behaviors, and diagnoses in persons with
      early to moderate dementia and sleep disturbance.
AB  - In this study, restless legs syndrome (RLS) risk factors, RLS-associated
      behaviors, and the ability to understand and answer an RLS diagnostic interview
      were investigated. In 23 older adults with early to moderate dementia and
      nighttime sleep disturbance, the most common risk factors for RLS were a periodic
      leg movement sleep index > 15 (54.55%), based on polysomnography, and use of
      selective serotonin reuptake inhibitors (SSRIs) (34.78%). The most common RLS
      associated behaviors were repetitious mannerisms (56.52%) and general
      restlessness (34.78%), according to direct observation from research assistants.
      Finally, older adults with early to moderate dementia were unable to understand
      and reliably answer the RLS diagnostic interview. Older persons with mild to
      moderate dementia and sleep disturbance may require objective diagnostics to
      identify RLS.

PMID- 20043251
TI  - Delusion and confabulation: overlapping or distinct distortions of reality?
AB  - Delusion is commonly defined as a false belief and associated with psychiatric
      illness like schizophrenia, whereas confabulation is typically described as a
      false memory and associated with neurological disorder like amnesia. Yet delusion
      and confabulation both involve the endorsement of distorted representations of
      reality, whether about the present or the personal past. Moreover, differences in
      aetiology need not dictate mutual exclusivity with regard to underlying cognitive
      mechanisms. In response to the growing interest in commonalities and differences
      between delusion and confabulation, this Special Issue brings together
      contributors from diverse fields to consider the relations between these two
      symptoms. Although approaches and opinions differ, all of our contributors share
      common aims of clarifying theoretical conceptions and exploring boundaries so as
      to advance understanding of the cognitive neuropsychiatry of both delusion and
      confabulation. After introducing each contribution, we highlight some common
      themes and unanswered questions.

PMID- 20043252
TI  - Conservation of species, volume, and belief in patients with Alzheimer's disease:
      the issue of domain specificity and conceptual impairment.
AB  - Two studies investigated whether patients with Alzheimer's disease (AD) suffer
      high-level and category-specific impairment in the conceptual domain of living
      things. In Experiment 1, AD patients and healthy young and healthy elderly
      controls took part in three tasks: the conservation of species, volume, and
      belief. All 3 tasks required tracking an object's identity in the face of
      irrelevant but salient transformations. Healthy young and elderly controls
      performed at or near ceiling on all tasks. AD patients were at or near ceiling on
      the volume and belief tasks, but only about half succeeded on the species task.
      Experiment 2 demonstrated that the results were not due to simple task demands.
      AD patients' failure to conserve species indicates that they are impaired in
      their theoretical understanding of living things, and their success on the volume
      and belief tasks suggests that the impairment is domain-specific. Two hypotheses
      are put forward to explain the phenomenon: The first, a category-specific
      account, holds that the intuitive theory of biology undergoes pervasive
      degradation; the second, a hybrid domain-general/domain-specific account, holds
      that impairment to domain-general processes such as executive function interacts
      with core cognition, the primitive elements that are the foundation of domain
      specific knowledge.

PMID- 20043253
TI  - Sexual assault histories and evening drinking among young american men in a high
      risk drinking environment.
AB  - This study surveyed young American men traveling to Tijuana, Mexico from San
      Diego, California for a weekend night out, collecting responses both southbound
      at the outset of the evening and northbound upon return at the end of the
      evening. Among 650 males, we examined the relationship between sexual histories
      and attitudes and alcohol use, both historically and on their night in Tijuana.
      Respondents with a history of coercing sex drank more in Tijuana and were more
      likely to binge drink. Although estimating sexual assaults committed by these
      males on the evening in question was not possible, this research establishes the
      link between a history of sexual assault and the blood alcohol concentration of
      young men resulting from an evening in a timeout environment.

PMID- 20043254
TI  - Assessing maladaptive responses to the stress of being at risk of HIV Infection
      among HIV-negative gay men in New York City.
AB  - The aim of this study was to examine the psychometric properties and preliminary
      validity of a newly developed 16-item measure to assess maladaptive responses to
      the stress of being at risk for HIV infection among HIV-negative gay men. The
      measure consisted of three factors: (a) fatalistic beliefs about maintaining an
      HIV-negative serostatus, (b) reduced perceived severity of HIV infection due to
      advances in medical treatment of HIV and AIDS, and (c) negative affective states
      associated with the risk of HIV infection. A total of 285 HIV-negative gay men at
      a counseling program in New York City participated in the study. Confirmatory
      factor analyses supported the three-factor model as an acceptable model fit: non
      normed fit index = .91, comparative fit index = .92, goodness-of-fit index = .90,
      and root mean square error of approximation = .07. The measure and its subscales
      obtained in this sample achieved adequate internal consistency coefficients.
      Construct validity was supported by significant and positive associations with
      internalized homophobia, depression, self-justifications for the last unprotected
      anal intercourse (UAI), and actual UAI with casual sex partners. Understanding
      the dynamics of maladaptive responses to the epidemic and intense anxieties
      elicited by HIV risk among HIV-negative gay men living in a place of high
      seroprevalence provides useful information to guide psychosocial interventions in
      the population.

PMID- 20043255
TI  - Natural phenolic compounds from medicinal herbs and dietary plants: potential use
      for cancer prevention.
AB  - Natural phenolic compounds play an important role in cancer prevention and
      treatment. Phenolic compounds from medicinal herbs and dietary plants include
      phenolic acids, flavonoids, tannins, stilbenes, curcuminoids, coumarins, lignans,
      quinones, and others. Various bioactivities of phenolic compounds are responsible
      for their chemopreventive properties (e.g., antioxidant, anticarcinogenic, or
      antimutagenic and anti-inflammatory effects) and also contribute to their
      inducing apoptosis by arresting cell cycle, regulating carcinogen metabolism and
      ontogenesis expression, inhibiting DNA binding and cell adhesion, migration,
      proliferation or differentiation, and blocking signaling pathways. This review
      covers the most recent literature to summarize structural categories and
      molecular anticancer mechanisms of phenolic compounds from medicinal herbs and
      dietary plants.

PMID- 20043256
TI  - Coffee intake and risk of colorectal cancer among Chinese in Singapore: the
      Singapore Chinese Health Study.
AB  - We prospectively investigated whether coffee consumption was associated with
      decreased risk of colorectal cancer and whether cigarette smoking and stage of
      disease modify the association in the Singapore Chinese Health Study. During the
      first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort
      of over 60,000 middle-aged or older Chinese men and women living in Singapore.
      Baseline dietary exposures were assessed through in-person interviews using a
      validated food frequency questionnaire. The relation between coffee consumption
      and colorectal cancer risk was assessed by proportional hazards (Cox) regression.
      No overall association between coffee intake and colorectal cancer was observed.
      However, in analysis by subsite and stage restricted to ever smokers, the coffee
      colon cancer association became statistically significant for advanced disease (P
      for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35
      0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared
      with those who drank no coffee or less than 1 cup per day. Although there is a
      null association between coffee intake and risk of colorectal cancer overall,
      coffee may protect against smoking related advanced colon cancer.

PMID- 20043257
TI  - Fruits and vegetables in relation to prostate cancer in Japanese men: the Japan
      Public Health Center-Based Prospective Study.
AB  - Although dietary risk factors may differ between localized and advanced prostate
      cancer, data on associations between the consumption of fruits and vegetables and
      risk of localized and advanced cancers are limited. We examined associations
      between fruit and vegetable consumption and risk of prostate cancer in a Japanese
      population. During 1995-1998, a validated food frequency questionnaire was
      administered to 43,475 men aged 45-74 yr. During 321,061 person-years of follow
      up until the end of 2004, 339 cases of prostate cancer were identified.
      Consumption of fruits or total vegetables was not associated with a decreased
      risk of total prostate cancer, with corresponding multivariate hazard ratios of
      the highest vs. lowest quartiles of 1.09 (95% CI = 0.77-1.53; trend P = 0.39) for
      fruits and 1.33 (95% CI = 0.93-1.91; trend P = 0.52) for total vegetables. Also,
      no association was observed for intake of either fruits or vegetables (total or
      any subtype) with localized or advanced prostate cancer. This prospective cohort
      study suggests that consumption of fruits or vegetables may not be associated
      with the risk of either localized or advanced prostate cancer in Japanese men.
      However, the possibility of confounding by detection bias on the risk of
      localized cancer could not be totally ruled out.

PMID- 20043259
TI  - The effects of storage time and sampling season on the stability of serum 25
      hydroxy vitamin D and androstenedione.
AB  - Knowledge of the stability of serum samples stored in large biobanks is pivotal
      for reliable assessment of hormone-dependent disease risks. We studied the
      effects of sample storage time and season of serum sampling on the stability of
      25-hydroxy vitamin D (25-OHD) and androstenedione in a stratified random sample
      of 402 women, using paired sera from the Finnish Maternity Cohort. Serum samples
      selected were donated between 6 and 24 yr ago. The storage time did not affect
      serum 25-OHD and androstenedione levels. However, there was a significant mean
      difference in the 25-OHD levels of sera withdrawn during winter (first sample)
      vs. during summer (second sample; -18.4 nmol/l, P <or= 0.001). Also at the
      individual level, there were significant differences in average 25-OHD levels
      between individuals with the paired sera taken at winter-winter compared with
      other alternatives (summer-winter, winter-summer, and summer-summer). The
      androstenedione levels showed no such differences. Long-term storage does not
      affect serum 25-OHD and androstenedione levels, but sampling season is an
      important determinant of 25-OHD levels. Stored serum samples can be used to study
      disease associations with both hormones. However, sampling season needs to be
      taken into account for 25-OHD by considering matching and stratification and, if
      possible, serial sampling.

PMID- 20043258
TI  - Dietary iron intake and risk of endometrial cancer: a population-based case
      control study in Shanghai, China.
AB  - Dietary red meat and animal fat have been linked to endometrial cancer (EC) risk,
      but the impact of bioavailable iron in animal-derived foods has been less well
      studied. Our objective was to investigate the effects of iron and fats on the
      risk of EC in a large, population-based, case-control study. The Shanghai
      Endometrial Cancer Study enrolled 1,204 EC cases and 1,212 controls who completed
      in-person interviews, including a food frequency questionnaire. Animal-derived
      iron and fat intakes were calculated from dietary intakes and food composition
      tables. Logistic regression models were used to evaluate independent and joint
      effects of iron and fat on EC risk. Animal-derived iron intake was positively
      associated with EC risk [adjusted OR = 1.9; 95% CI = 1.4-2.7, P(trend) < 0.01,
      highest vs. lowest quartile], predominantly after menopause (OR = 2.2; 95%CI =
      1.4-3.4, P(trend) < 0.01) and in women with BMI >or= 25 kg/m(2)(OR = 3.2; 95% CI
      = 1.4-7.5 in postmenopausal obese women, P(trend) < 0.01). Animal-derived fat was
      also associated with postmenopausal EC risk (OR = 1.7; 95% CI = 1.2-2.5, P(trend)
      < 0.01). Multiplicative interactions between animal-derived iron and BMI or
      animal-derived fat intake were not observed. Animal-derived iron intake is
      associated with increased risk of EC after menopause and among obese women.
      Avoidance of animal-derived (heme) iron may reduce the risk of EC in these women.

PMID- 20043260
TI  - Effects of beta-ionone on mammary carcinogenesis and antioxidant status in rats
      treated with DMBA.
AB  - Recent chemopreventive studies from our group showed that dietary beta -ionone
      inhibited 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis by
      the inhibition of cell proliferation and apoptosis initiation. In this study, we
      examined the chemopreventive effects of varied doses of dietary beta -ionone on
      the development and growth of DMBA-induced rat mammary tumors as well as plasma
      antioxidant status. beta -ionone treatment groups were given 9, 18, and 36
      mmol/kg in the AIN76A diet starting 2 wk prior to DMBA administration and
      continuing for the 24 wk. Results showed that tumor incidence was dose
      dependently reduced by 35.4, 68.3, and 87.8%, respectively, compared to the
      positive control. Tumor sizes were dose dependently smaller, and tumor weight was
      less in each group, each rat, and each tumor compared to the positive control (P
      < 0.05). A significant decrease in lipid peroxidation was observed in the tumor
      induced rats treated with dietary beta -ionone, whereas the plasma activities of
      antioxidant enzymes such as glutathione peroxidase, glutathione reductase,
      superoxide dismutase, and the nonenzymatic antioxidant glutathione were increased
      in the beta -ionone treated rats when compared to control. The levels of catalase
      and lactate dehydrogenase were remarkably decreased in the beta -ionone treated
      groups compared to the positive control group. These results suggest that dietary
      beta -ionone has biologically relevant antioxidant activity and plays a
      chemopreventive role against DMBA induced mammary gland tumors.

PMID- 20043261
TI  - Selenium decreases thyroid cancer cell growth by increasing expression of GADD153
      and GADD34.
AB  - Selenium (Se) supplementation is reported to decrease the incidence and total
      mortality of cancer. Whereas in vitro and in vivo studies have shown a decrease
      in prostate, lung, and liver cancers, this has not been shown in thyroid cancer.
      ARO (anaplastic), NPA (BRAF positive papillary), WRO (BRAF negative papillary),
      and FRO (follicular) cells treated with 150 microM seleno-l-methionine (SM) were
      assessed for viability at 24, 48, and 72 h. Treated FRO cells were examined for
      cell cycle using flow cytometry, for apoptosis using terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL) assay, and for gene
      expression using microarray. Genes identified as upregulated were confirmed by
      real-time PCR (RT-PCR) and proteins by Western blot analysis. SM treatment
      significantly decreased the proliferation of all cell lines. TUNEL assay showed
      no evidence of apoptosis, and flow cytometry showed a significant cell-cycle
      arrest in S (271% increase, P = 0.006) and G2/M (61% increase, P = 0.002)
      compared to control. Microarray revealed 21 differentially expressed genes with
      greater than twofold change. A relative overexpression of growth arrest and DNA
      damage inducible (GADD)34 and GADD153 in treated cells was confirmed with RT-PCR
      and Western blot. SM inhibits thyroid cancer cell proliferation through a time
      dependent upregulation of the GADD family of genes and arrest in S and G2/M
      phases of the cell cycle. This is the first report of selenium induced inhibition
      of thyroid cancer cell growth.

PMID- 20043262
TI  - Chemomodulatory effect of Trachyspermum ammi on murine skin and forestomach
      papillomagenesis.
AB  - Trachyspermum ammi seed consumed worldwide as a spice ingredient is much valued
      for its medicinal properties. However, it has not been investigated for its
      cancer chemopreventive efficacy. Herein, the chemopreventive effect of different
      doses (2%, 4%, and 6%) of test diets of Trachyspermum ammi seeds were examined on
      DMBA-induced skin and B(a)P-induced forestomach papillomagenesis, inducibility of
      drug metabolizing phase I and phase II enzymes, antioxidant enzymes(catalase,
      superoxide dismutase, glutathione peroxidase, glyoxalase I), reduced glutathione
      content, and peroxidative damage. Results exhibited a significant reduction in
      the skin as well as the forestomach tumor multiplicity with respect to all doses
      of test diet as compared to the control group. Biochemical assays revealed a
      significant increase in the activities of phase I enzymes especially with 6% test
      diet. A concomitant increase in the activities of the phase II enzymes and
      antioxidant enzymes were observed in Trachyspermum ammi treated groups. The
      content of reduced glutathione was significantly elevated, whereas the
      peroxidative damage along with lactate dehydrogenase activity exhibited a
      significant reduction with all the three doses of test diet. These findings were
      indicative of chemopreventive potential of Trachyspermum ammi seeds against
      carcinogenesis.

PMID- 20043263
TI  - Deoxycholic acid and selenium metabolite methylselenol exert common and distinct
      effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon
      cancer cells.
AB  - The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause
      compensatory hyperproliferation of colonic epithelial cells and consequently
      increase colon cancer risk. On the other hand, there is increasing evidence for
      the efficacy of certain forms of selenium (Se) as anticancer nutrients.
      Methylselenol has been hypothesized to be a critical Se metabolite for anticancer
      activity in vivo. In this study, we demonstrated that both DCA (75-300
      micromol/l) and submicromolar methylselenol inhibited colon cancer cell
      proliferation by up to 64% and 63%, respectively. In addition, DCA and
      methylselenol each increased colon cancer cell apoptosis rate by up to twofold.
      Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction
      with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an
      increase in the G1 and G2 fractions with a concomitant drop only in the S-phase.
      Although both DCA and methylselenol significantly promoted apoptosis and
      inhibited cell growth, examination of mitogen-activated protein kinase (MAPK)
      pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2,
      p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the
      molecular basis for opposite effects of methylselenol and DCA on colon
      tumorigenesis.

PMID- 20043264
TI  - Effect of black raspberry extract in inhibiting NFkappa B dependent
      radioprotection in human breast cancer cells.
AB  - Black raspberry extracts (RSE) have been shown to inhibit cancer cell growth and
      stimulate apoptosis. Also, studies have demonstrated that RSE inhibits
      transcriptional regulators including NFkappa B. Accordingly, we investigated the
      effect of RSE in inhibiting radiation (IR) induced NFkappa B mediated
      radioprotection in breast adenocarcinoma cells. MCF-7 cells were exposed to IR
      (2Gy), treated with RSE (0.5, 1.0, 2.0 micro g/ml) or treated with RSE (1.0 micro
      g/ml) followed by IR exposure, and harvested after 1, 3, 6, 24, 48, and 72 h.
      NFkappa B DNA-binding activity was measured by EMSA and phosphorylated Ikappa
      Balpha by immunoblotting. Expression of IAP1, IAP2, XIAP and survivin were
      measured by QPCR and immunoblotting. Cell survival was measured using MTT assay
      and cell death using Caspase-3/7 activity. Effect of RSE on IR induced MnSOD,
      TNFalpha, IL-1alpha and MnSOD activity was also determined. RSE inhibited NFkappa
      B activity in a dose-dependent manner. Also, RSE inhibited IR-induced sustained
      activation of NFkappa B, and NFkappa B regulated IAP1, IAP2, XIAP, and survivin.
      In addition, RSE inhibited IR-induced TNFalpha, IL-1alpha, and MnSOD levels and
      MnSOD activity. RSE suppressed cell survival and enhanced cell death. These
      results suggest that RSE may act as a potent radiosensitizer by overcoming the
      effects of NFkappa B mediated radioprotection in human breast cancer cells.

PMID- 20043265
TI  - Differential antineoplastic effects of butyrate in cells with and without a
      functioning DNA mismatch repair.
AB  - The aim of this study was to investigate the differential antineoplastic effects
      of butyrate in cells with and without a functional mismatch repair and to
      determine the molecular mechanisms underlying these effects. SW48 colon cancer
      cells in which the MLH1 gene is silenced by promoter hypermethylation and
      demethylated SW48 cells in which the MLH1 gene is reexpressed were treated with
      butyrate (0-5mM) for 8 days and the effects on cell number, MLH1 gene promoter
      methylation, and expression of two cell cycle regulatory genes, CDK4 and GADD45A,
      were assessed. Butyrate suppressed viable cell number (P < 0.001) and reduced
      MLH1 promoter methylation (P < 0.05) in SW48 cells. However, in demethylated SW48
      cells, butyrate caused an increase in viable cells (P < 0.05) and promoter
      methylation (P < 0.05). CDK4 expression was downregulated by butyrate exposure,
      but the effect was significantly greater for demethylated SW48 cells (P = 0.025).
      Butyrate treatment caused upregulation of GADD45A expression in SW48 cells but
      downregulation of GADD45A expression in demethylated SW48 cells (P = 0.045). This
      study supports the hypothesis that butyrate has more potent antineoplastic
      effects on colon cancer cells with MLH1 dysfunction. Differential expression of
      key cell cycle regulatory genes may explain some of the molecular mechanisms
      underlying these effects.

PMID- 20043266
TI  - The 10t,12c isomer of conjugated linoleic acid inhibits fatty acid synthase
      expression and enzyme activity in human breast, colon, and prostate cancer cells.
AB  - The objective of this study was to determine whether downregulation of fatty acid
      synthase (FAS) expression and/or inhibition of its activity by the two major CLA
      isomers, 10t,12c and 9c,11t CLA, could contribute to their inhibitory effect on
      the growth of human breast (MCF-7), colon (HT-29) and prostate (LNCaP) cancer
      cell lines. We first confirmed and extended the results of others showing that
      the inhibitory action of CLA on proliferation is dependent on the cell type as
      well as the structure of the isomer, the 10,12 isomer being a more potent
      inhibitor than the 9,11 isomer in the concentration range 25-100 microM. By
      Western analysis, we showed that 10,12 CLA downregulated FAS expression in all of
      the cell lines in a concentration-dependent manner, but the 9,11 isomer had no
      effect. Both isomers inhibited FAS enzyme activity, but 10,12 CLA was again more
      potent than the 9,11 isomer. Our results suggest that downregulation of FAS by
      10,12 CLA, but not by the 9,11 isomer, as well as inhibition of FAS enzyme
      activity by both isomers, may contribute to growth inhibition of cancer cells but
      only at relatively high concentrations.

PMID- 20043267
TI  - Effects of nutrition relevant mixtures of phytoestrogens on steroidogenesis,
      aromatase, estrogen, and androgen activity.
AB  - Phytoestrogens (PEs) are naturally occurring plant components produced in a large
      range of plants. They can induce biologic responses in vertebrates by mimicking
      or modulating the action or production of endogenous hormones. This study
      examined mixtures of 12 food relevant PEs for effects on steroid hormone
      production, aromatase activity, estrogenic activity, and for interaction with the
      androgen receptor. The results show that a mixture of all tested PEs increased
      estradiol production and decreased testosterone production in H295R human adrenal
      corticocarcinoma cells, indicating an induced aromatase activity. Furthermore,
      exposure of the H295R cells to isoflavonoids caused a decrease in testosterone
      production, and various mixtures of PEs significantly stimulated MCF-7 human
      breast adenocarcinoma cell growth and induced aromatase activity in JEG-3
      choriocarcinoma cells. The estrogenic effect in the MCF7 cells of the
      isoflavonoid mixture and coumestrol was supported by an observed increase in
      progesterone receptor protein expression as well as a decreased ERalpha
      expression. Overall, the results support that nutrition-relevant concentrations
      of PEs both alone and in mixtures possess various endocrine disrupting effects,
      all of which need to be considered when assessing the effects on human health.

PMID- 20043268
TI  - Effects of population policy and economic reform on the trend in fertility in
      Guangdong province, China, 1975-2005.
AB  - An analysis of data mainly from China's 1990 and 2000 censuses and 2005 mini
      census shows how fertility decline between 1975 and 2005 in the province of
      Guangdong has been influenced by both fertility policy and economic and social
      development. Guangdong's development since 1975 has been very rapid and has
      attracted huge numbers of migrants from other provinces. The analysis of the
      province's fertility trend from 1975 shows clearly the influence of fertility
      policy on the trend. The analysis also shows that economic development has
      brought about large changes in population composition by urban/rural residence,
      education, occupation, and migration status, which, together with large fertility
      differentials by these characteristics, have contributed substantially to
      Guangdong's fertility decline, in large part through changes in proportions
      currently married.

PMID- 20043269
TI  - Subreplacement fertility in the West before the baby boom: past and current
      perspectives.
AB  - Between 1920 and 1940, fertility dropped below replacement level in many Western
      countries. In today's scholarly literature, the drop is usually explained as a
      temporary reaction to the exceptional conditions of the inter-war period. This
      paper confronts that interpretation with the interpretations offered by scholars
      writing between the wars. According to leading demographers of the time, low
      fertility was due not to war or economic crisis, but rather to processes that now
      tend to be associated with the Second Demographic Transition, including
      secularization, individualization, rising consumerism, and women's emancipation.
      Since these were seen as structural features of modernization, most inter-war
      scholars argued that subreplacement fertility would remain an obstinate feature
      of modern society for an extended period of time.

PMID- 20043270
TI  - Across-task long-term priming: interaction of task readiness and automatic
      retrieval.
AB  - When humans carry out actions in response to external stimulation, they acquire
      associations between the stimulus and the action it triggered. When the same
      stimulus is used in two different tasks, the retrieval of associations compiled
      in the competing task hampers current performance. Previous research suggests
      that this across-task priming depends on the task set for the preceding task
      remaining active across the switch of tasks and, thus, competing with the
      activations needed for the new task. We present two experiments investigating
      this notion. Participants switched between two semantic classification tasks. In
      Experiment 1, participants switched between short runs of the two tasks. Across
      task priming was observed on switch and repeat trials. In Experiment 2,
      participants switched between longer runs of the two tasks. Across-task priming
      was markedly reduced on repeat trials. The data suggest that whether or not
      across-task priming affects behaviour after the switch trial depends, amongst
      others, on whether the task set necessary for the previous task spills into the
      repeat trials. The implications of these findings for mechanisms of cognitive and
      mnemonic control are discussed.

PMID- 20043271
TI  - Effects of viewing time, fixations, and viewing strategies on visual memory for
      briefly presented natural objects.
AB  - We investigated the impact of viewing time and fixations on visual memory for
      briefly presented natural objects. Participants saw a display of eight natural
      objects arranged in a circle and used a partial report procedure to assign one
      object to the position it previously occupied during stimulus presentation. At
      the longest viewing time of 7,000 ms or 10 fixations, memory performance was
      significantly higher than at the shorter times. This increase was accompanied by
      a primacy effect, suggesting a contribution of another memory component-for
      example, visual long-term memory (VLTM). We found a very limited beneficial
      effect of fixations on objects; fixated objects were only remembered better at
      the shortest viewing times. Our results revealed an intriguing difference between
      the use of a blocked versus an interleaved experimental design. When trial length
      was predictable, in the blocked design, target fixation durations increased with
      longer viewing times. When trial length was unpredictable, fixation durations
      stayed the same for all viewing lengths. Memory performance was not affected by
      this design manipulation, thus also supporting the idea that the number and
      duration of fixations are not closely coupled to memory performance.

PMID- 20043272
TI  - Metacognitive monitoring and strategic behaviour in working memory performance.
AB  - Research indicates that cognitive age differences can be influenced by
      metacognitive factors. This research has generally focused on simple memory
      tasks. Age differences in working memory (WM) performance are pronounced, but are
      typically attributed to basic cognitive deficits rather than metacognitive
      factors. However, WM performance can be influenced by strategic behaviour that
      might be driven by metacognitive monitoring. In the current project, we attempted
      to connect these lines of research by examining age differences in metacognitive
      WM monitoring and strategies. In Experiment 1, younger and older adult
      participants completed a computerized operation span task in conditions that
      either required or did not require monitoring reports. Participants in the
      monitoring condition predicted and postdicted global performance for each block
      and rated their responses following each trial within a block. In Experiment 2,
      participants also reported their trial-level strategic approach. In contrast to
      the age equivalence typically found for simple memory monitoring, results
      demonstrated age differences in WM monitoring accuracy. Overall age differences
      in strategy use were not found, but using effective strategies benefited older
      adults' performance more than younger adults'. Furthermore, age-related
      differences in the WM task appear to be mediated by the accuracy of performance
      monitoring.

PMID- 20043273
TI  - Two measures of task-specific inhibition.
AB  - Inhibition has been implicated as an important mechanism for task-set control,
      ensuring the efficient selection of the to-be-performed task over alternative
      possibilities. Across three experiments we demonstrated the effects of two
      potentially different types of task inhibition. The first is the inhibition of a
      task that concurrently affords an incongruent response, which is labelled
      dimension inhibition (Goschke, 2000). Using targets that afford three tasks, we
      demonstrated that this only occurs when a single alternative task affords an
      incongruent response, with the inhibition being specific to that task. The second
      type of inhibition that we observed was backwards inhibition-the suppression of a
      recently abandoned task-set (Mayr & Keele, 2000). Unlike dimension inhibition,
      backwards inhibition was not triggered by the response incongruence of the
      unperformed tasks, or even whether the target afforded responses via the
      unperformed tasks. These two purported types of inhibition did not co-occur, and
      neither did the factors of response congruence and whether that task was recently
      abandoned interact. We therefore suggest that task-specific inhibition can be
      applied/triggered differently depending upon the paradigm, perhaps depending upon
      the extent to which alternative tasks, and therefore potentially other responses,
      are triggered by the target.

PMID- 20043274
TI  - A large-scale comparison of prospective and retrospective memory development from
      childhood to middle age.
AB  - We present the first large-scale comparison of prospective memory (PM) and
      retrospective memory (RM) from 8 to 50 years of age (N = 318,614). Participants
      in an Internet study were asked to remember to click on a smiley face (single
      trial event-based PM test) and to indicate whether/where a picture had changed
      from study to test (single-trial RM test), in both cases after retention
      intervals filled with working-memory tests and questionnaires. Both PM and RM
      improved during childhood; however, whereas maximal PM was reached by teenagers,
      with approximately linear decline through the 20s-40s, RM continued to improve
      through the 20s and 30s. On both tests, females outperformed males and achieved
      maximal success at earlier ages. Strikingly, 10-11-year-old girls performed
      significantly better than females in their late 20s on the PM test. The presence
      of the smiley face at encoding and temporal uncertainty (expecting it "later"
      rather than at the "end" of the test) both benefited PM; these effects decreased
      and increased, respectively, from childhood to middle age. The findings
      demonstrate that in a cross-sectional study (a) developmental trajectories are
      qualitatively different between PM and RM, and (b) the relative influence of PM
      cues differs between younger and older ages.

PMID- 20043275
TI  - Advancing deep inferior epigastric artery perforator flap breast reconstruction
      through multidetector row computed tomography: an evolution in preoperative
      imaging.
AB  - Perforator flaps have become increasingly popular tools in microvascular breast
      reconstruction. Previous criticism of these techniques, particularly deep
      inferior epigastric artery perforator (DIEAP) flap, have included the variability
      in the path of the perforators through the rectus muscle, the tedious and time
      consuming need to look for and to clamp various perforators to determine the
      "dominant" perforator, and uncertainty whether adequate perforators exist
      following previous abdominal surgery. Preoperative imaging has contributed
      significantly to the reliability, speed, and minimal donor site morbidity of
      these procedures. A major evolution in preoperative imaging has been the
      introduction of multidetector row computed tomography (MDCT) as a replacement for
      color duplex imaging. There are multiple advantages to MDCT with few
      disadvantages, and so it has become the gold standard for the preoperative
      planning of DIEAP flap breast reconstruction in the practices of both authors,
      completely eliminating the use of color duplex. Improvements in the preoperative
      understanding of the anatomy of each perforator from its branching pattern in the
      subcutaneous fat, to its perforation through the anterior rectus sheath and
      rectus muscle toward the groin facilitate this type of surgery in a manner only
      possible with MDCT and not duplex imaging.

PMID- 20043276
TI  - On the bumpy road towards 'personalized medicine'.

PMID- 20043278
TI  - Dose and context dependent effects of Myc on epidermal stem cell proliferation
      and differentiation.
AB  - Myc is activated in many tumours, yet, paradoxically, stimulates differentiation
      in mammalian epidermis. To test whether the epidermis responds differently to
      different levels of Myc, we treated K14MycER transgenic mice with a range of
      concentrations of the inducing agent, 4-hydroxy-tamoxifen (4OHT). Proliferation
      was stimulated at all levels of Myc activity; sebocyte differentiation was
      stimulated at low and intermediate levels; and interfollicular epidermal
      differentiation at intermediate and high levels. Mutational inactivation of the
      Myc p21 activated kinase 2 (PAK2) phosphorylation sites increased Myc activity
      and further enhanced epidermal differentiation. We conclude that Myc induced
      differentiation acts as a fail-safe device to prevent uncontrolled proliferation
      and neoplastic conversion of epidermal stem cells expressing high levels of Myc.

PMID- 20043279
TI  - ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the
      channel-activating protease 1.
AB  - Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar
      epithelial cells (AEC) provides the driving force for removal of fluid from the
      alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8)
      activates ENaC in vitro in various expression systems. To study the role of
      CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we
      generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional
      Cre-loxP-mediated recombination. Deficiency of CAP1/Prss8 in AEC induced in vitro
      a 40% decrease in ENaC-mediated sodium currents. Sodium-driven alveolar fluid
      clearance (AFC) was reduced in CAP1/Prss8-deficient mice, due to a 48% decrease
      in amiloride-sensitive clearance, and was less sensitive to beta(2)-agonist
      treatment. Intra-alveolar treatment with neutrophil elastase, a soluble serine
      protease activating ENaC at the cell surface, fully restored basal AFC and the
      stimulation by beta(2)-agonists. Finally, acute volume-overload increased
      alveolar lining fluid volume in CAP1/Prss8-deficient mice. This study reveals
      that CAP1 plays a crucial role in the regulation of ENaC-mediated alveolar sodium
      and water transport and in mouse lung fluid balance.

PMID- 20043280
TI  - Decoding the evolution of a breast cancer genome.
AB  - Shah et al have recently reported the first successful sequencing of the entire
      genome of a solid tumour (Shah et al, 2009). Philippe Bedard and Christos
      Sotiriou analyse their findings as well as the challenges of applying the study
      of cancer genomes to clinical cancer care.

PMID- 20043282
TI  - Tuning afferent synapses of hippocampal interneurons by neuropeptide Y.
AB  - Cholecystokinin (CCK)-expressing basket cells encompass a subclass of inhibitory
      GABAergic interneurons that regulate memory-forming oscillatory network activity
      of the hippocampal formation in accordance to the emotional and motivational
      state of the animal, conveyed onto these cells by respective extrahippocampal
      afferents. Various excitatory and inhibitory afferent and efferent synapses of
      the hippocampal CCK basket cells express serotoninergic, cholinergic,
      cannabinoid, and benzodiazepine sensitive receptors, all contributing to their
      functional plasticity. We explored whether CCK basket cells are modulated by
      neuropeptide Y (NPY), one of the major local neuropeptides that strongly inhibits
      hippocampal excitability and has significant effect on its memory function. Here,
      using GAD65-GFP transgenic mice for prospective identification of CCK basket
      cells and whole-cell patch-clamp recordings, we show for the first time that
      excitatory and inhibitory inputs onto CCK basket cells in the dentate gyrus of
      the hippocampus are modulated by NPY through activation of NPY Y2 receptors. The
      frequency of spontaneous and miniature EPSCs, as well as the amplitudes of
      stimulation-evoked EPSCs were decreased. Similarly, the frequency of both
      spontaneous and miniature IPSCs, and the amplitudes of stimulation-evoked IPSCs
      were decreased after NPY application. Most of the effects of NPY could be
      attributed to a presynaptic site of action. Our data provide the first evidence
      that the excitatory and inhibitory inputs onto the CCK basket cells could be
      modulated by local levels of NPY, and may change the way these cells process
      extrahippocampal afferent information, influencing hippocampal function and its
      network excitability during normal and pathological oscillatory activities.

PMID- 20043281
TI  - ConteXt of change--X inactivation and disease.
AB  - Epigenetic regulation is important for stable maintenance of cell identity. For
      continued function of organs and tissues, illegitimate changes in cell identity
      must be avoided. Failure to do so can trigger tumour development and disease. How
      epigenetic patterns are established during cell differentiation has been explored
      by studying model systems such as X inactivation. Mammals balance the X-linked
      gene dosage between the sexes by silencing of one of the two X chromosomes in
      females. This is initiated by expression of the non-coding X-inactive specific
      transcript (Xist) RNA and depends on specific cellular contexts, in which
      essential silencing factors are expressed. Normally X inactivation is initiated
      in early embryogenesis, but recent reports identified instances where Xist is
      expressed and can initiate gene repression. Here we describe the features that
      characterize the cellular permissivity to initiation of X inactivation and note
      that these can also occur in cancer cells and in specific haematopoietic
      progenitors. We propose that embryonic pathways for epigenetic regulation are re
      established in adult progenitor cells and tumour cells. Understanding their
      reactivation will deepen our understanding of tumourigenesis and may be exploited
      for cancer therapy.

PMID- 20043283
TI  - Differential regulation of synaptic plasticity of the hippocampal and the
      hypothalamic inputs to the anterior thalamus.
AB  - The hippocampus projects to the anterior thalamic nuclei both directly and
      indirectly via the mammillary bodies, but little is known about the
      electrophysiological properties of these convergent pathways. Here we
      demonstrate, for the first time, the presence of long-term plasticity in anterior
      thalamic nuclei synapses in response to high- and low-frequency stimulation (LFS)
      in urethane-anesthetized rats. We compared the synaptic changes evoked via the
      direct vs. the indirect hippocampal pathways to the anterior thalamus, and found
      that long-term potentiation (LTP) of the thalamic field response is induced
      predominantly through the direct hippocampal projections. Furthermore, we have
      estimated that that long-term depression (LTD) can be induced only after
      stimulation of the indirect connections carried by the mammillothalamic tract.
      Interestingly, basal synaptic transmission mediated by the mammillothalamic tract
      undergoes use-dependent, BDNF-mediated potentiation, revealing a distinct form of
      plasticity specific to the diencephalic region. Our data indicate that the
      thalamus does not passively relay incoming information, but rather acts as a
      synaptic network, where the ability to integrate hippocampal and mammillary body
      inputs is dynamically modified as a result of previous activity in the circuit.
      The complementary properties of these two parallel pathways upon anterior
      thalamic activity reveal that they do not have duplicate functions.

PMID- 20043284
TI  - Matrix metalloproteinase-9 reversibly affects the time course of NMDA-induced
      currents in cultured rat hippocampal neurons.
AB  - Matrix Metalloproteinase 9 (MMP-9) has been demonstrated to play a crucial role
      in maintenance of NMDA receptor-dependent LTP and in lateral mobility of these
      receptors. However, the effect of MMP-9 on NMDA receptor (NMDAR) functional
      properties is unknown. For this purpose we have investigated the impact of
      recombinant MMP-9 on the whole-cell NMDAR-mediated current responses in cultured
      hippocampal neurons. Treatment with MMP-9 induced a reversible acceleration of
      desensitization and deactivation kinetics but had no effect on current amplitude.
      Interestingly, phorbol ester, a PKC activator known to enhance NMDAR lateral
      mobility, induced kinetic changes of currents similar to those produced by MMP-9.
      In conclusion, our results show that MMP-9 reversibly modulates the NMDAR
      kinetics and raise a possibility that this modulation could be related to the
      lateral mobility of these receptors.

PMID- 20043285
TI  - Acute stress disrupts paired pulse facilitation and long-term potentiation in rat
      dorsal hippocampus through activation of glucocorticoid receptors.
AB  - Cognitive functions such as learning and memory are widely believed to depend on
      patterns of short- and long-term synaptic plasticity. Factors, such as acute
      stress, which affect learning and memory, may do so by altering patterns of
      synaptic plasticity in distinct neural circuits. Numerous studies have examined
      the effects of acute stress on long-term synaptic plasticity; however, few have
      examined its influence on short-term plasticity. The present experiments directly
      assessed the effects of acute stress on short-term synaptic plasticity as
      measured by paired pulse facilitation (PPF) of excitatory postsynaptic potentials
      recorded from rat dorsal hippocampus (dHip) in vivo. Long-term potentiation (LTP)
      was also examined. Acute stress induced by exposure to an elevated platform
      impaired PPF and LTP in the dHip. Pretreatment of rats exposed to stress with
      mifepristone (RU38486; 10 mg kg-1) blocked the stress-induced impairment of both
      PPF and LTP. These data demonstrate that activation of glucocorticoid receptors
      during acute stress disrupts normal patterns of both PPF and LTP in the dHip.

PMID- 20043286
TI  - Covalently linked wall proteins in ascomycetous fungi.
AB  - The covalently linked wall proteins of Saccharomyces cerevisiae and Candida
      albicans and to a lesser extent of Candida glabrata have been extensively
      studied. Here we describe some of their main structural features and discuss
      their conservation in other ascomycetous fungi. We also discuss the hybrid nature
      of many wall proteins and the frequent occurrence of families of wall proteins
      with a common multi-domain structure. Finally, some quantitative data regarding
      wall proteins are presented.

PMID- 20043287
TI  - Dried blood spot for hepatitis C virus serology and molecular testing.
AB  - We investigated the performance of dried blood spots (DBS) in hepatitis C virus
      (HCV) diagnosis using modified commercial tests. Paired DBS and serum samples
      were collected from 200 patients: 100 patients with anti-HCV antibodies (anti
      HCV), including 62 patients with detectable serum HCV RNA, and 100 patients
      without anti-HCV. The DBS sample consisted of three drops of approximately 50
      microL of whole blood applied to a paper card, which was then stored at -20
      degrees C within 48 hours of collection. Using the Ortho HCV 3.0 enzyme-linked
      immunosorbent assay kit on DBS, we observed both a specificity and sensitivity of
      99% in detecting anti-HCV. HCV RNA was detected on DBS in 60/62 (97%) patients
      with detectable serum HCV RNA, which was then successfully quantified in 55
      samples (89%) using the Cobas TaqMan HCV test. A good correlation was observed
      between the DBS HCV RNA concentration and the serum level (r(2) = 0.95; P <
      0.001). HCV genotyping was successfully performed on DBS samples, with a full
      concordance between the 14 paired DBS and serum samples (genotypes 1-4).
      CONCLUSION: This study presents DBS as a reliable alternative to serum specimens
      for detecting anti-HCV, quantifying HCV RNA and genotyping HCV. DBS may increase
      the opportunities for HCV testing and treatment follow-up in hard-to-reach
      individuals.

PMID- 20043290
TI  - Mast cells in innate and adaptive immunity to infection.
AB  - In June 2009, the National Institute of Allergy and Infectious Diseases (NIAID),
      Division of Allergy, Immunology and Transplantation (DAIT), sponsored a workshop
      entitled Mast Cells in Innate and Adaptive Immunity. International experts in
      mast cell biology discussed recent advances in the field and future areas of
      research aimed at advancing our understanding of the importance of mast cells in
      shaping nonallergic, adaptive immunity to infection.

PMID- 20043295
TI  - Evaluations of Bayesian and maximum likelihood methods in PK models with below
      quantification-limit data.
AB  - Pharmacokinetic (PK) data often contain concentration measurements below the
      quantification limit (BQL). While specific values cannot be assigned to these
      observations, nevertheless these observed BQL data are informative and generally
      known to be lower than the lower limit of quantification (LLQ). Setting BQLs as
      missing data violates the usual missing at random (MAR) assumption applied to the
      statistical methods, and therefore leads to biased or less precise parameter
      estimation. By definition, these data lie within the interval [0, LLQ], and can
      be considered as censored observations. Statistical methods that handle censored
      data, such as maximum likelihood and Bayesian methods, are thus useful in the
      modelling of such data sets. The main aim of this work was to investigate the
      impact of the amount of BQL observations on the bias and precision of parameter
      estimates in population PK models (non-linear mixed effects models in general)
      under maximum likelihood method as implemented in SAS and NONMEM, and a Bayesian
      approach using Markov chain Monte Carlo (MCMC) as applied in WinBUGS. A second
      aim was to compare these different methods in dealing with BQL or censored data
      in a practical situation. The evaluation was illustrated by simulation based on a
      simple PK model, where a number of data sets were simulated from a one
      compartment first-order elimination PK model. Several quantification limits were
      applied to each of the simulated data to generate data sets with certain amounts
      of BQL data. The average percentage of BQL ranged from 25% to 75%. Their
      influence on the bias and precision of all population PK model parameters such as
      clearance and volume distribution under each estimation approach was explored and
      compared.

PMID- 20043296
TI  - Short-term in-home intervention reduces depressive symptoms in Early Head Start
      Latina mothers of infants and toddlers.
AB  - Depressive symptoms may compromise the ability of low-income Latina mothers with
      limited English language proficiency to parent their infants or toddlers. Eighty
      Early Head Start Latina mothers with limited English language proficiency were
      randomized to an advanced practice nurse-delivered, culturally tailored, in-home
      psychotherapy intervention, or to usual care. Repeated measures regression
      analysis showed a significantly greater decrease in depressive symptoms for
      intervention mothers compared to the usual care group at 22 and 26 weeks (4 weeks
      post intervention). Intervention mothers' reports of their child's aggression
      diminished significantly from T1 to T4 compared to usual care mothers (p = .03).
      Self-efficacy appeared to only partially mediate the intervention effect, and
      maternal health moderated the intervention impact. Results indicate that the
      intervention reduced depressive symptoms and, compared to previous studies in
      this population, retention of mothers in both intervention and control conditions
      was improved.

PMID- 20043297
TI  - Telomerase enzyme inhibition (TEI) and cytolytic therapy in the management of
      androgen independent osseous metastatic prostate cancer.
AB  - BACKGROUND: Recurrent prostate cancer can be osseous, androgen independent and
      lethal. The purpose is to discern the efficacy of synthetic small molecule
      telomerase enzyme inhibitors (TEI) alone or in combination with other cytotoxic
      therapies in controlling metastatic osseous prostate cancer. METHODS: C4-2B was
      pre-treated with a match or mismatch TEI for 6 weeks and then inoculated into
      nude mice subcutaneously or intraosseously. In a separate experiment, untreated
      C4-2B was injected into femur of nude mice. The mice were divided into seven
      systemic "combination" treatment groups of control, Ad-BSP-E1a virus, docetaxel,
      mismatch and match TEI. Serum PSA was followed longitudinally. Histology analyses
      and histomorphometry were performed. Repeated measure analysis was applied for
      statistical analysis and Bonferroni method was used in multiple comparisons.
      RESULTS: In the pre-treated study, the PSA of match treated cells in subcutaneous
      or intraosseous model was significantly lower than mismatch TEI or PBS treated
      group (P < 0.05). Histology revealed increased fibrosis, apoptosis and decreased
      PSA staining in the match TEI treated subcutaneous xenografts. In the combination
      treatment study, the PSA was significantly lower in single/double treatment and
      triple treatment than control (P < 0.05). Histology revealed that triple therapy
      mice had normal femur architecture. Histomorphometrics revealed that the area of
      femur tumor and woven bone was significantly positively correlated (P = 0.007).
      CONCLUSIONS: Multiple lines of data point toward the efficacy of systemically
      administered telomerase inhibitors. Combining cytotoxic regimens with telomerase
      inhibitors could be beneficial in controlling prostate cancer. Clinical trials
      are warranted to explore the efficacy of TEI in prostate cancer.

PMID- 20043298
TI  - Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing
      oxidative stress and inflammation and by inducing apoptosis.
AB  - The present study was designed to investigate the protective efficacy of eugenol
      against skin cancer and probe into the mechanistic aspects. Skin tumors were
      initiated by applying 160 nmol DMBA and promoted by twice weekly applications of
      8.5 nmol TPA for 28 wk. All mice developed tumors by 13 wk of promotion. However,
      in mice pretreated with 30 microL eugenol, no tumors were detected until 8 wk
      (following anti-initiation protocol) and until 14 wk (following antipromotion
      protocol) of tumor promotion. PCNA and TUNEL immunohistochemistry of tumors
      revealed eugenol to ameliorate cell proliferation and elevate apoptosis
      respectively. The effect of eugenol was assessed on specific stages of
      carcinogenesis. Initiation with DMBA led to a significant upregulation of p53
      expression with a concomitant increase in p21(WAF1) levels in epidermal cells
      indicating induction of damage to the DNA. However, pretreatment with eugenol led
      to overexpression of these genes, which probably helped stimulate apoptosis of
      the initiated cells. To ascertain the molecular mechanisms implicated in the
      antitumor promoting activity of eugenol, its effect was investigated on markers
      of tumor promotion and inflammation: ODC activity and iNOS and COX-2 expression,
      and on levels of proinflammatory cytokines (IL-6, TNF-alpha, and PGE(2)). Eugenol
      markedly inhibited all. Eugenol also inhibited the upstream signaling molecule:
      NF-kappaB, which regulates the expression of these genes. TPA-induced depletion
      of cutaneous GSH and antioxidant enzymes armory was also precluded by eugenol.
      From these results, it could be concluded that eugenol markedly protects against
      chemically induced skin cancer and acts possibly by virtue of its
      antiproliferative, anti-inflammatory, and antioxidant activities.

PMID- 20043300
TI  - PROTEOMICS: ten years in the field.

PMID- 20043299
TI  - Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D
      receptor FokI polymorphism collectively modulate beta-catenin activity in colon
      cancer cells.
AB  - The activity of beta-catenin, commonly dysregulated in human colon cancers, is
      inhibited by the vitamin D receptor (VDR), and this mechanism is postulated to
      explain the putative anti-cancer activity of vitamin D metabolites in the colon.
      We investigated the effect of a common FokI restriction site polymorphism (F/f)
      in the human VDR gene as well as the effect of anti-tumorigenic 1,25
      dihydroxyvitamin D(3) (1,25D) and pro-tumorigenic lithocholic acid (LCA) VDR
      ligands on beta-catenin transcriptional activity. Furthermore, the influence of a
      major regulatory protein of beta-catenin, the APC tumor suppressor gene, on VDR
      dependent inhibition of beta-catenin activity was examined. We report herein that
      beta-catenin-mediated transcription is most effectively suppressed by the VDR
      FokI variant F/M4 when 1,25D is limiting. Using Caco-2 colorectal cancer (CRC)
      cells, it was observed that VDR ligands, 1,25D and LCA, both suppress beta
      catenin transcriptional activity, though 1,25D exhibited significantly greater
      inhibition. Moreover, 1,25D, but not LCA, suppressed endogenous expression of the
      beta-catenin target gene DKK-4 independent of VDR DNA-binding activity. These
      results support beta-catenin sequestration away from endogenous gene targets by
      1,25D-VDR. This activity is most efficiently mediated by the FokI gene variant
      F/M4, a VDR allele previously associated with protection against CRC.
      Interestingly, we found the inhibition of beta-catenin activity by 1,25D-VDR was
      significantly enhanced by wild-type APC. These results reveal a previously
      unrecognized role for 1,25D-VDR in APC/beta-catenin cross talk. Collectively,
      these findings strengthen evidence favoring a direct effect on the Wnt-signaling
      molecule beta-catenin as one anti-cancer target of 1,25D-VDR action in the
      colorectum.

PMID- 20043303
TI  - Activation of allylic C-F bonds: palladium-catalyzed allylic amination of 3,3
      difluoropropenes.

PMID- 20043304
TI  - NMR spectra of terminal oxo gold and platinum complexes: relativistic DFT
      predictions.

PMID- 20043305
TI  - A practical heterogeneous catalyst for the Suzuki, Sonogashira, and Stille
      coupling reactions of unreactive aryl chlorides.

PMID- 20043306
TI  - The biosynthesis of liposidomycin-like A-90289 antibiotics featuring a new type
      of sulfotransferase.

PMID- 20043307
TI  - Preparation of biomolecule microstructures and microarrays by thiol-ene
      photoimmobilization.
AB  - A mild, fast and flexible method for photoimmobilization of biomolecules based on
      the light-initiated thiol-ene reaction has been developed. After investigation
      and optimization of various surface materials, surface chemistries and reaction
      parameters, microstructures and microarrays of biotin, oligonucleotides,
      peptides, and MUC1 tandem repeat glycopeptides were prepared with this
      photoimmobilization method. Furthermore, MUC1 tandem repeat glycopeptide
      microarrays were successfully used to probe antibodies in mouse serum obtained
      from vaccinated mice. Dimensions of biomolecule microstructures were shown to be
      freely controllable through photolithographic techniques, and features down to 5
      microm in size covering an area of up to 75x25 mm were created. Use of a confocal
      laser microscope with a UV laser as UV-light source enabled further reduction of
      biotin feature size opening access to nanostructured biochips.

PMID- 20043308
TI  - Pathways and substrate specificity of DMSP catabolism in marine bacteria of the
      Roseobacter clade.
AB  - The volatiles released by Phaeobacter gallaeciensis, Oceanibulbus indolifex and
      Dinoroseobacter shibae have been investigated by GC-MS, and several MeSH-derived
      sulfur volatiles have been identified. An important sulfur source in the oceans
      is the algal metabolite dimethylsulfoniopropionate (DMSP). Labelled [2H6]DMSP was
      fed to the bacteria to investigate the production of volatiles from this compound
      through the lysis pathway to [2H6]dimethylsulfide or the demethylation pathway to
      [2H3]-3-(methylmercapto)propionic acid and lysis to [2H3]MeSH. [2H6]DMSP was
      efficiently converted to [2H3]MeSH by all three species. Several DMSP derivatives
      were synthesised and used in feeding experiments. Strong dealkylation activity
      was observed for the methylated ethyl methyl sulfoniopropionate and
      dimethylseleniopropionate, as indicated by the formation of EtSH- and MeSeH
      derived volatiles, whereas no volatiles were formed from
      dimethyltelluriopropionate. In contrast, the dealkylation activity for
      diethylsulfoniopropionate was strongly reduced, resulting in only small amounts
      of EtSH-derived volatiles accompanied by diethyl sulfide in P. gallaeciensis and
      O. indolifex, while D. shibae produced the related oxidation product diethyl
      sulfone. The formation of diethyl sulfide and diethyl sulfone requires the lysis
      pathway, which is not active for [2H6]DMSP. These observations can be explained
      by a shifted distribution between the two competing pathways due to a blocked
      dealkylation of ethylated substrates.

PMID- 20043309
TI  - Jewels in the pearl.

PMID- 20043310
TI  - Coadsorption of hydrogen and CO on hydrogen pre-covered PtRu/Ru(0001) surface
      alloys.
AB  - The influence of pre-adsorbed hydrogen on the adsorption of CO on well-defined
      PtRu/Ru(0001) surface alloys and the modification of the adsorption properties of
      both adsorbate species due to coadsorption was studied by a combination of
      temperature-programmed desorption and infrared spectroscopic measurements. The
      hydrogen binding strength is weakened both by surface alloy formation and by CO
      coadsorption. In the densely packed coadsorbate layers, which can be formed after
      CO post-adsorption, the adsorption properties of the adsorbed CO molecules are
      also affected significantly. Depending on the Pt surface concentration, the CO
      adsorption process on hydrogen pre-covered surfaces is blocked to a different
      extent with a decreasing blocking tendency for Pt-rich alloys.

PMID- 20043311
TI  - Angle-independent structural color in colloidal amorphous arrays.

PMID- 20043313
TI  - Exploring chemical modifications for siRNA therapeutics: a structural and
      functional outlook.
AB  - RNA interference (RNAi) is a post-transcriptional gene silencing mechanism
      induced by small interfering RNAs (siRNAs) and micro-RNAs (miRNAs), and has
      proved to be one of the most important scientific discoveries made in the last
      century. The robustness of RNAi has opened up new avenues in the development of
      siRNAs as therapeutic agents against various diseases including cancer and HIV.
      However, there had remained a lack of a clear mechanistic understanding of
      messenger RNA (mRNA) cleavage mediated by Argonaute2 of the RNA-induced silencing
      complex (RISC), due to inadequate structural data. The X-ray crystal structures
      of the Argonaute (Ago)-DNA-RNA complexes reported recently have proven to be a
      breakthrough in this field, and the structural details can provide guidelines for
      the design of the next generation of siRNA therapeutics. To harness siRNAs as
      therapeutic agents, the prudent use of various chemical modifications is
      warranted to enhance nuclease resistance, prevent immune activation, decrease off
      target effects, and to improve pharmacokinetic and pharmacodynamic properties.
      The focus of this review is to interpret the tolerance of various chemical
      modifications employed in siRNAs toward RNAi by taking into account the crystal
      structures and biochemical studies of Ago-RNA complexes. Moreover, the challenges
      and recent progress in imparting druglike properties to siRNAs along with their
      delivery strategies are discussed.

PMID- 20043312
TI  - Semisynthetic latrunculin derivatives as inhibitors of metastatic breast cancer:
      biological evaluations, preliminary structure-activity relationship and molecular
      modeling studies.
AB  - The microfilament cytoskeleton protein actin plays an important role in cell
      biology and affects cytokinesis, morphogenesis, and cell migration. These
      functions usually fail and become abnormal in cancer cells. The marine-derived
      macrolides latrunculins A and B, from the Red Sea sponge Negombata magnifica, are
      known to reversibly bind actin monomers, forming 1:1 stoichiometric complexes
      with G-actin, disrupting its polymerization. To identify novel therapeutic agents
      for effective treatment of metastatic breast cancer, several semisynthetic
      derivatives of latrunculin A with diverse steric, electrostatic, and hydrogen
      bond donor and acceptor properties were rationally prepared. Analogues were
      designed to modulate the binding affinity toward G-actin. Examples of these
      reactions are esterification, acetylation, and N-alkylation. Semisynthetic
      latrunculins were then tested for their ability to inhibit pyrene-conjugated
      actin polymerization, and subsequently assayed for their antiproliferative and
      anti-invasive properties against MCF7 and MDA-MB-231 cells using MTT and invasion
      assays, respectively.

PMID- 20043314
TI  - Phenyl-oxazoles, a new family of inverse agonists at the H(3) histamine receptor.

PMID- 20043315
TI  - From machine learning to natural product derivatives that selectively activate
      transcription factor PPARgamma.

PMID- 20043316
TI  - Recovery and reuse of nanoparticles by tuning solvent quality.

PMID- 20043317
TI  - ALDH(+)/CD44(+)/CD24(-) expression in cells from body cavity fluids.
AB  - BACKGROUND: Enhanced expression of aldehyde dehydrogenase 1 (ALDH1) and
      phenotypic markers (CD44(+)/CD24(-)) in stem cells from breast tumors has been
      reported. This study was undertaken to monitor expression of these markers in
      cells from body cavity fluids of female patients suspected to have a malignancy.
      METHODS: Cells from peritoneal and pleural fluids of 100 female patients were
      examined by diagnostic cytology and analyzed by laser flow cytometry for enhanced
      ALDH1 expression. Cells from 36 body cavity fluids with ALDH1(bright)
      fluorescence were then analyzed for the expression of CD44 and CD24 markers.
      RESULTS: In samples positive for malignancy, ALDH1(bright) cells with both
      SSC(low) and SSC(high) were seen. In 15 body cavity fluids positive for
      malignancy, the percentage of ALDH1(bright) cells ranged from 0.26 to 6.34% of
      the total cells. The percentage of ALDH1(bright) cells with CD44(+)/CD24(-)
      expression in these samples ranged from 0.02 to 3.66%. ALDH1(bright) cells with
      CD44(+)/CD24(-) expression were also present in body cavity fluids of patients in
      whom diagnostic cytology could not detect any malignancy. However, the percentage
      of ALDH1(bright) and CD44(+)/CD24(-) cells amongst the 21 body cavity fluids with
      negative cytology was lower than that of samples with malignancy. CONCLUSIONS:
      Expression of ALDH1(bright) and the CD44(+)/CD24(-) phenotype in body cavity
      fluids in which diagnostic cytology could not find any malignant cells suggests
      that this phenotype may not be restricted to the putative breast tumor stem
      cells. It is possible that only subsets of cells with this phenotype are the
      putative breast tumor stem cells.

PMID- 20043318
TI  - Expression pattern of acetylated alpha-tubulin in porcine spermatogonia.
AB  - Mammalian spermatogonial stem cells reside on the basement membrane of the
      seminiferous tubules. The mechanisms responsible for maintenance of spermatogonia
      at the basement membrane are unclear. Since acetylated alpha-tubulin (Ac-alpha
      Tu) is a component of long-lived, stable microtubules and deacetylation of alpha
      tubulin enhances cell motility, we hypothesized that acetylation of alpha-tubulin
      might be associated with positioning of spermatogonia at the basement membrane.
      The expression pattern of Ac-alpha-Tu at different stages of testis development
      was characterized by immunohistochemistry for Ac-alpha-Tu and spermatogonia
      specific proteins (PGP 9.5, DAZL). In immature pig testes, Ac-alpha-Tu was
      present exclusively in gonocytes at 1 week of age, and in a subset of
      spermatogonia at 10 weeks of age. At this age, spermatogonia are migrating toward
      the tubule periphery and Ac-alpha-Tu appeared polarized toward the basement
      membrane. In adult pig testes, Ac-alpha-Tu was detected in few single or paired
      spermatogonia at the basement membrane as well as in spermatids and spermatozoa.
      Only undifferentiated (DAZL-), proliferating (determined by BrdU incorporation)
      spermatogonia expressed high levels of Ac-alpha-Tu. Comparison with the
      expression pattern of beta-tubulin and tyrosinated alpha-tubulin confirmed that
      only Ac-alpha-Tu is specific to germ cells. The unique pattern of Ac-alpha-Tu in
      undifferentiated germ cells during postnatal development suggests that
      posttranslational modifications of microtubules may play an important role in
      recruiting and anchoring spermatogonia at the basement membrane. Mol. Reprod.
      Dev. 77: 348-352, 2010. (c) 2009 Wiley-Liss, Inc.

PMID- 20043320
TI  - Hepatitis C virus-induced up-regulation of protein phosphatase 2A inhibits
      histone modification and DNA damage repair.
AB  - The molecular mechanisms underlying hepatocarcinogenesis in chronic viral
      hepatitis are poorly understood. A potential tumorigenic pathway could involve
      protein phosphatase 2A (PP2A) and protein arginine methyltransferase 1 (PRMT1),
      because both enzymes are dysregulated in chronic hepatitis C, and both enzymes
      have been involved in chromatin remodeling and DNA damage repair. We used cell
      lines that allow the inducible expression of hepatitis C virus proteins
      (UHCV57.3) and of the catalytic subunit of PP2A (UPP2A-C8) as well as Huh7.5
      cells infected with recombinant cell culture-derived hepatitis C virus (HCVcc) to
      study epigenetic histone modifications and DNA damage repair. The induction of
      viral proteins, the overexpression of PP2Ac, or the infection of Huh7.5 cells
      with HCVcc resulted in an inhibition of histone H4 methylation/acetylation and
      histone H2AX phosphorylation, in a significantly changed expression of genes
      important for hepatocarcinogenesis, and inhibited DNA damage repair.
      Overexpression of PP2Ac in NIH-3T3 cells increased anchorage-independent growth.
      These changes were partially reversed by the treatment of cells with the methyl
      group donor S-adenosyl-L-methionine (SAMe). CONCLUSION: Hepatitis C virus-induced
      overexpression of PP2Ac contributes to hepatocarcinogenesis through dysregulation
      of epigenetic histone modifications. The correction of defective histone
      modifications by S-adenosyl-L-methionine makes this drug a candidate for
      chemopreventive therapies in patients with chronic hepatitis C who are at risk
      for developing hepatocellular carcinoma.

PMID- 20043319
TI  - Growth hormone and gene expression of in vitro-matured rhesus macaque oocytes.
AB  - Growth hormone (GH) in rhesus macaque in vitro oocyte maturation (IVM) has been
      shown to increase cumulus expansion and development of embryos to the 9-16 cell
      stage in response to 100 ng/ml recombinant human GH (r-hGH) supplementation
      during IVM. Although developmental endpoints for metaphase II (MII) oocytes and
      embryos are limited in the macaque, gene expression analysis can provide a
      mechanism to explore GH action on IVM. In addition, gene expression analysis may
      allow molecular events associated with improved cytoplasmic maturation to be
      detected. In this study, gene expression of specific mRNAs in MII oocytes and
      cumulus cells that have or have not been exposed to r-hGH during IVM was
      compared. In addition, mRNA expression was compared between in vitro and in vivo
      matured metaphase II (MII) oocytes and germinal vesicle (GV)-stage oocytes. Only
      2 of 17 genes, insulin-like growth factor 2 (IGF2) and steroidogenic acute
      regulator (STAR), showed increased mRNA expression in MII oocytes from the 100
      ng/ml r-hGH treatment group compared with other IVM treatment groups, implicating
      insulin-like growth factor (IGF) and steroidogenesis pathways in the oocyte
      response to GH. The importance of IGF2 is notable, as expression of IGF1 was not
      detected in macaque GV-stage or MII oocytes or cumulus cells.

PMID- 20043321
TI  - Technological progresses in monoclonal antibody production systems.
AB  - Monoclonal antibodies (mAbs) have become vitally important to modern medicine and
      are currently one of the major biopharmaceutical products in development.
      However, the high clinical dose requirements of mAbs demand a greater
      biomanufacturing capacity, leading to the development of new technologies for
      their large-scale production, with mammalian cell culture dominating the
      scenario. Although some companies have tried to meet these demands by creating
      bioreactors of increased capacity, the optimization of cell culture productivity
      in normal bioreactors appears as a better strategy. This review describes the
      main technological progresses made with this intent, presenting the advantages
      and limitations of each production system, as well as suggestions for
      improvements. New and upgraded bioreactors have emerged both for adherent and
      suspension cell culture, with disposable reactors attracting increased interest
      in the last years. Furthermore, the strategies and technologies used to control
      culture parameters are in constant evolution, aiming at the on-line
      multiparameter monitoring and considering now parameters not seen as relevant for
      process optimization in the past. All progresses being made have as primary goal
      the development of highly productive and economic mAb manufacturing processes
      that will allow the rapid introduction of the product in the biopharmaceutical
      market at more accessible prices.

PMID- 20043322
TI  - Estrogen stimulates female biliary epithelial cell interleukin-6 expression in
      mice and humans.
AB  - Females are more susceptible than males to several biliary tract diseases.
      Interleukin-6 (IL-6) is critical to triggering autoimmune reactions and
      contributes substantially to biliary epithelial cell (BEC) barrier function and
      wound repair, and estrogen differentially regulates IL-6 expression in various
      cell types. We hypothesized that estrogen might stimulate BEC IL-6 production.
      Exposure to physiologic levels of estradiol, in vitro, increased female mouse BEC
      (mBEC) IL-6 messenger RNA (mRNA) and protein expression, but either inhibited or
      had no effect on male mBECs. Female mBECs expressed higher concentrations of
      estrogen receptor-alpha (ERalpha) mRNA and protein and were also more dependent
      on estradiol for survival, in vitro. In vivo, elevated estrogen during estrous
      cycling in mice, and estrogen treatment of mice harboring an ERalpha(+) human
      cholangiocarcinoma resulted in increased BEC IL-6 mRNA and tumor viability,
      respectively. Both responses could be blocked by an ERalpha antagonist. Human
      cholangiocarcinoma cell lines differentially expressing ERalpha were treated with
      specific ERalpha and ERbeta agonists/antagonists to further test the relationship
      between estrogen stimulation, ERalpha expression, and IL-6 production. Results
      show that ERalpha, and not the underlying BEC sex, was responsible for estrogen
      induced IL-6 production. Estrogen-induced proliferation of ERalpha-expressing
      cholangiocarcinoma was blocked by anti-IL-6 antibodies, indicating that at least
      some of the estrogen-trophic effects are mediated via IL-6. Finally, an
      association between ERalpha, IL-6, and phosphorylated signal transducer and
      activator of transcription 3 (pSTAT3) signaling was shown in female-predominant
      polycystic livers using immunohistochemical analyses, including multiplex quantum
      dot labeling. CONCLUSION: Estrogens stimulate IL-6 production in non-neoplastic
      female BECs and in neoplastic BECs expressing ERalpha. An association between
      these signaling pathways was demonstrated for female-predominant polycystic
      livers and might also influence autoimmune hepatitis, primary biliary cirrhosis,
      and cholangiocarcinogenesis.

PMID- 20043323
TI  - Changes in the expression of methionine adenosyltransferase genes and S
      adenosylmethionine homeostasis during hepatic stellate cell activation.
AB  - Hepatic stellate cell (HSC) activation is an essential event during liver
      fibrogenesis. Methionine adenosyltransferase (MAT) catalyzes biosynthesis of S
      adenosylmethionine (SAMe), the principle methyl donor. SAMe metabolism generates
      two methylation inhibitors, methylthioadenosine (MTA) and S-adenosylhomocysteine
      (SAH). Liver cell proliferation is associated with induction of two nonliver
      specific MATs: MAT2A, which encodes the catalytic subunit alpha2, and MAT2beta,
      which encodes a regulatory subunit beta that modulates the activity of the MAT2A
      encoded isoenzyme MATII. We reported that MAT2A and MAT2beta genes are required
      for liver cancer cell growth that is induced by the profibrogenic factor leptin.
      Also, MAT2beta regulates leptin signaling. The strong association of MAT genes
      with proliferation and leptin signaling in liver cells led us to examine the role
      of these genes during HSC activation. MAT2A and MAT2beta are induced in culture
      activated primary rat HSCs and HSCs from 10-day bile duct ligated (BDL) rat
      livers. HSC activation led to a decline in intracellular SAMe and MTA levels, a
      drop in the SAMe/SAH ratio, and global DNA hypomethylation. The decrease in SAMe
      levels was associated with lower MATII activity during activation. MAT2A
      silencing in primary HSCs and MAT2A or MAT2beta silencing in the human stellate
      cell line LX-2 resulted in decreased collagen and alpha-smooth muscle actin
      (alpha-SMA) expression and cell growth and increased apoptosis. MAT2A knockdown
      decreased intracellular SAMe levels in LX-2 cells. Activation of extracellular
      signal-regulated kinase and phosphatidylinositol-3-kinase signaling in LX-2 cells
      required the expression of MAT2beta but not that of MAT2A. CONCLUSION: MAT2A and
      MAT2beta genes are induced during HSC activation and are essential for this
      process. The SAMe level falls, resulting in global DNA hypomethylation.

PMID- 20043324
TI  - Primary lymphoma of bone in adult patients.
AB  - BACKGROUND: The low incidence of primary lymphoma of bone (PLB) has led to
      discrepancies in classification as well as difficulty in prognostication. The
      authors of this report used the Surveillance, Epidemiology, and End Results
      (SEER) database to analyze a large, population-based cohort of adult patients
      with this disease. The database provides a standardized classification and
      documentation of outcomes and enables a meaningful evaluation of prognostic
      factors. METHODS: The SEER database was used to identify all patients who were
      diagnosed with PLB from 1973 through 2005. Survival was analyzed with the Kaplan
      Meier method, and the influence of clinical parameters on survival was analyzed
      with the log-rank test. A Cox proportional hazards model was used for
      multivariate analysis. RESULTS: Fifteen hundred adult patients with PLB were
      analyzed. The 5-year and 10-year survival rates for adult patients were 58% and
      45%, respectively. Multivariate analysis revealed that younger age and localized
      disease were independent predictors of survival. It is noteworthy that the
      incidence of disease, as determined by the annual percentage change, increased
      during the study period (P < .05). CONCLUSIONS: This analysis of a large cohort
      of adults with PLB indicated that the only identifiable prognostic indicators
      were localized disease and younger age. The authors concluded that future
      treatment for patients with PLB need to be based on strict staging criteria and
      adherence to successful published protocols using collaborative clinical trials.

PMID- 20043325
TI  - Gene-environment interplay.

PMID- 20043327
TI  - Pancreatic cysts: preoperative diagnosis and clinical management.
AB  - Preoperative diagnosis of pancreatic cysts benefits from integrating the
      clinical, radiological, and cytological features. As patient management
      algorithms evolve to increasingly nonsurgical options, accuracy in distinguishing
      mucinous from nonmucinous and benign from malignant mucinous cysts is important.
      This review focuses on pseudocysts, serous cystadenomas, intraductal papillary
      mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Patients with
      pseudocysts almost always present with pancreatitis and are usually medically
      managed. Radiological studies reveal a unilocular cyst mostly in the pancreatic
      tail. Cyst fluid is thin, with high amylase but low carcinoembryonic antigen
      (CEA) levels. DNA mutations are absent. Serous cystadenomas are benign and do not
      require resection. Patients are usually asymptomatic and have microcystic or
      macrocystic masses anywhere in the pancreas. Cytology is frequently
      nondiagnostic. CEA and amylase levels are low. DNA analysis may reveal loss of
      heterozygosity (LOH) at 3p if associated with Von Hippel-Lindau disease.
      Neoplastic mucinous cysts are highly variable in their presentation. Most are
      resected. Mucinous cystic neoplasms typically arise in the body or tail of the
      pancreas of middle-aged women and demonstrate a septated cyst without dilatation
      of the main pancreatic duct. Branch duct IPMNs are more common in the pancreatic
      head of elderly men. Main duct dilatation correlates with main duct or combined
      type IPMN. Both types of mucinous cysts produce variable amounts of mucin.
      Cytologically nonmalignant but atypical epithelial cells, even when scant, are an
      indication of a high risk for malignancy. High CEA level supports a mucinous
      cyst, as do KRAS mutation and good quality DNA levels. KRAS mutation and multiple
      LOH support malignancy.

PMID- 20043328
TI  - Drink, drugs, and the QT interval.
AB  - The effects of several prescription and illicitly-used drugs on
      electrocardiographic repolarization are well documented, most frequently
      manifested as prolongation of the corrected QT (QTc) interval. The combination of
      multiple repolarization-modulating drugs taken in high dosage can occasionally
      lead to extreme abnormalities of the QTc interval and ST-segment on the surface
      ECG, which can lead to the erroneous diagnosis of underlying myocardial ischemia
      and inappropriate treatment. We report on one such case in which the acute
      management of a syncopal patient was detrimentally influenced by
      misinterpretation of a very unusual ECG.

PMID- 20043329
TI  - Serum cardiac troponin I is related to increased left ventricular wall thickness,
      left ventricular dysfunction, and male gender in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Serum cardiac troponin I (cTnI) is a sensitive and specific marker of
      myocardial injury. However, a systematic evaluation of cTnI in hypertrophic
      cardiomyopathy (HCM) patients has not been performed. HYPOTHESIS: The purpose of
      this study is to evaluate cTnI and determine its relationship to clinical
      features in HCM. METHODS: We studied serum cTnI in 162 consecutive HCM patients.
      RESULTS: Serum cTnI ranged from 0.01 to 0.83 ng/mL (mean, 0.068 +/- 0.100 ng/mL)
      and was higher in male patients (P < .001), those with atrial fibrillation (P =
      .033), and left ventricular (LV) systolic dysfunction (P = .046). Serum cTnI
      values were also correlated with maximum LV wall thickness (r = 0.30, P < .001),
      LV end-systolic diameter (r = 0.20, P = .012), and E/Ea (peak early transmitral
      filling velocity/early diastolic mitral annulus velocity; r = 0.24, P = .004).
      Serum cTnI levels were not significantly different among New York Heart
      Association (NYHA) functional class and there was no difference between patients
      with or without LV outflow tract obstruction; although B-type natriuretic peptide
      (BNP) levels showed significant difference in those variables. Serum cTnI had
      very weak correlation with BNP values (r = 0.18, P = .023). Multivariate analysis
      revealed an independent relationship between cTnI and maximum LV wall thickness,
      E/Ea, and male gender. CONCLUSIONS: In patients with HCM, serum cTnI was
      associated with important clinical indices such as maximum LV wall thickness, LV
      dysfunction, and male gender. Serum cTnI seemed to have clinical significance
      different from that of BNP and may not be reflecting cardiac load but the LV
      remodeling process in HCM.

PMID- 20043330
TI  - Heparin-induced thrombocytopenia associated with pulmonary embolism.
AB  - Type II heparin-induced thrombocytopenia (HIT) is a potentially severe adverse
      effect of heparin treatment triggered by an immune response. Although most cases
      occur in patients receiving unfractioned heparin, HIT can also arise after low
      molecular-weight heparin (LMWH). We report a case of HIT in a postoperative
      orthopedic 75-year-old woman in treatment with LMWH (nadroparin) complicated by
      pulmonary embolism and treated successfully with recombinant hirudin. Early
      recognition and proper treatment are fundamental for the management of this life
      threatening disorder.

PMID- 20043331
TI  - Multi-plane mechanical dyssynchrony in cardiac resynchronization therapy.
AB  - BACKGROUND: The aims of this study were to assess the ability of several echo
      measures of dyssynchrony to predict CRT response and to characterize the global
      effect of CRT. HYPOTHESIS: We hypothesized that after CRT there would be
      significant reductions in mechanical dyssynchrony in all 3 orthogonal planes of
      cardiac motion and that those patients with significant dyssynchrony prior to
      implant would have the best echocardiographic response. METHODS: Standard
      echocardiograms were performed pre-CRT and post-CRT (138 +/- 63d) in 70 heart
      failure patients. Longitudinal dyssynchrony was calculated as the standard
      deviation (SD) of time to peak systolic displacement and velocity of 12 segments
      from 3 apical views. Using midventricular short axis views and speckle-tracking
      methods, the SD of time to peak radial and circumferential strain in 6 segments
      were calculated. Cardiac resynchronization therapy echo response was defined as >
      or = 15% decrease in left ventricular end-systolic volume. RESULTS: Cardiac
      resynchronization therapy significantly improved systolic function in the
      longitudinal, radial, and circumferential planes. The CRT echo response rate was
      57%. Echo responders (CRT(R)) had significantly (P < .05) more dyssynchrony at
      baseline as compared to nonresponders (CRT(NR)). Cardiac resynchronization
      therapy significantly (P < .05) reduced longitudinal and radial, but not
      circumferential, dyssynchrony in CRT(R). Dyssynchrony was unchanged in CRT(NR).
      Receiver-operator characteristic (ROC) curve analysis indicated significant, but
      modest sensitivity and specificity for longitudinal and radial intraventricular
      dyssynchrony and for interventricular dyssynchrony. Combining radial and
      longitudinal dyssynchrony measures improved positive prediction of CRT response.
      CONCLUSIONS: Cardiac resynchronization therapy improves left ventricular function
      in 3 orthogonal planes of motion. Longitudinal, radial, and interventricular
      dyssynchrony modestly predict reverse remodeling.

PMID- 20043332
TI  - Images in cardiology. Macrovolt T-wave alternans.

PMID- 20043333
TI  - Slow heart-slow brain: consequence of short-term occupational exposure to toluene
      in a young woman: what is the real mechanism?
AB  - Herein we describe a case of acute occupational exposure to toluene in a 27-year
      old female patient, presented to the emergency department of our institute. On
      admission she had electrocardiographic signs of profound sinus bradycardia with
      sinus arrhythmia and low amplitude slow wave activity recorded on her
      electroencephalogram (EEG). The mechanisms underlying the cerebral and cardiac
      effects of toluene are also discussed.

PMID- 20043334
TI  - Myocardial perfusion profile in a young population with and without known
      coronary artery disease: comparison by gender.
AB  - BACKGROUND: More and more young people are being referred for evaluation or
      screening for coronary artery disease (CAD). However, the value of myocardial
      perfusion imaging (MPI) in this population is unclear, especially in the absence
      of symptoms. METHODS: The study sample included 1765 consecutive patients less
      than 51 years old who were referred to a major medical center for stress/rest MPI
      study. Clinical and MPI variables were compared between patients with and without
      known CAD, by gender. RESULTS: There were 1346 (76%) men and 419 (24%) women of
      mean age 44 +/- 6 years; 461 (26%) had known CAD. Stress-induced ischemia was
      detected in 321 patients (18.2%) and significant ischemia in 131 (7.4%); there
      was no difference in the rate or severity of ischemia by presence of symptoms.
      Among those without known CAD, the rate of stress-induced ischemia by MPI was
      significantly lower in women than men. On logistic regression analysis, the
      independent predictors of ischemia in men were high cholesterol, diabetes, angina
      during stress testing, ST depression, and smoking (P<.0001); and in women, the
      independent predictors were diabetes and high cholesterol. CONCLUSION: Known CAD
      and stress-induced ischemia are significantly more prevalent in young men than in
      young women, irrespective of risk factors. The independent predictors of ischemia
      differ between men and women.

PMID- 20043335
TI  - Irreversible end-stage heart failure in a young patient due to severe chronic
      hypocalcemia associated with primary hypoparathyroidism and celiac disease.
AB  - BACKGROUND: Chronic hypocalcemia may cause electrocardiographic (ECG) changes and
      mimic acute myocardial infarction. It has also been associated with reversible
      cardiac dysfunction. On the other hand cardiomyopathy and heart failure have been
      reported in patients with idiopathic hypoparathyroidism or celiac disease.
      CLINICAL CASE: A 39-year-old male was admitted to the emergency room with acute
      retrosternal pain and dyspnea. He exhibited severe hypocalcemia and acute renal
      failure. High creatine kinase (CK) levels did not correlate with biomarkers of
      myocardial necrosis (negative troponin test, heart type creatine kinase isoenzyme
      (CK-MB) < 1% of CK value). The ECG showed an extremely long QT interval (0.6 sec)
      and T-wave inversions on V(4) through V(6). The left ventricular ejection
      fraction (LVEF) was as low as 25%, while coronary angiography was normal.
      Investigation of the hypocalcemia revealed primary hypoparathyroidism
      (Parathyroid hormone (PTH) < 3 pg/ml) and concomitant celiac disease with
      positive antigliadin and endomysial antibodies. The cardiovascular episodes and
      the dilated heart failure were attributed to the chronic hypocalcemia since no
      other cause was found. The correction of hypocalcemia has not been sufficient to
      reverse the end-stage heart failure after more than 6 months of treatment, even
      though ECG abnormalities have receded, implying permanent cardiac impairment.
      CONCLUSION: This case demonstrates an unusual clinical condition where 2 calcium
      homeostasis disorders led to severe hypocalcemia with clinical manifestations of
      end-stage heart failure. The severe cardiac failure appeared to be nonreversible
      after calcium repletion suggesting permanent cardiac muscle dysfunction due to
      associated cardiomyopathy.

PMID- 20043336
TI  - Epidemiological association between uric acid concentration in plasma,
      lipoprotein(a), and the traditional lipid profile.
AB  - BACKGROUND: Elevated levels of uric acid in serum (SUA) or plasma (PUA) are
      increasingly related to cardiovascular disease. It is unclear whether they are
      independent risk factors or simply markers, reflecting association with other
      traditional risk factors. METHODS: We retrospectively assessed results of a lipid
      profile, including total cholesterol, low-density lipoprotein cholesterol (LDL
      C), high-density lipoprotein cholesterol (HDL-C), triglycerides, total
      cholesterol to HDL-C ratio (TC/HDL-C), the atherogenic index of plasma (AIP), and
      lipoprotein(a) (Lp[a]), in a large cohort of unselected adult outpatients.
      RESULTS: Hyperuricemic men displayed significantly increased values of
      triglycerides and AIP when compared with men with normal PUA levels. In
      hyperuricemic women, significant differences were observed for HDL-C,
      triglycerides, TC/HDL-C, and AIP compared with women with normal PUA levels. The
      percentage of patients with unfavorable values was statistically higher for
      triglycerides and AIP in hyperuricemic men; for HDL-C, triglycerides, TC/HDL-C,
      and AIP in hyperuricemic women. In multivariable linear regression analysis
      triglycerides, AIP, and TC/HDL-C were independently associated with PUA in women,
      whereas no significant association was observed in men. CONCLUSION: PUA
      measurement might be advisable in patients to identify those at increased risk of
      cardiovascular disease (CVD) who might benefit from further triage and
      intervention.

PMID- 20043337
TI  - Gender-related differences in coronary artery dimensions: a volumetric analysis.
AB  - BACKGROUND: Women consistently have poorer revascularization outcomes and more
      coronary vascular complications compared to men. This has been attributed to
      smaller coronary arteries, though limited data exist to support this assumption.
      HYPOTHESIS: By using volumetric data obtained from multidetector cardiovascular
      computed tomography (CCT), we sought to determine to what extent gender
      influences coronary artery dimensions and test the hypothesis that women would
      have smaller coronary dimensions even after normalizing for body surface area and
      cardiac mass. METHODS: CCT examinations completed on a 64-slice scanner were
      identified from a university cardiovascular database. Data sets from 50 women and
      44 men without coronary artery disease were selected for analysis. Cross
      sectional areas of proximal and distal segments of the left anterior descending
      (LAD), circumflex (LCx), and right coronary artery (RCA) were measured, blinded
      to patient gender. Measurements were compared using 2-sample t tests and linear
      regression analysis techniques accounting for body surface area (BSA) and left
      ventricular (LV) mass. RESULTS: Analysis of cross-sectional coronary artery
      areas, unadjusted for BSA and LV mass showed smaller coronary artery size in
      women compared to men in the proximal portion of both the LAD (P = .01) and RCA
      (P = .002), but no significant difference in the remaining coronary segments.
      CONCLUSION: Gender significantly impacts proximal LAD and RCA size. Differences
      in coronary artery dimensions may explain some, but not all excess gender-related
      risk with coronary artery revascularization, underscoring the importance of
      considering multiple contributing factors.

PMID- 20043338
TI  - The efficacy of statin therapy in patients with acute coronary syndromes and
      concomitant carotid disease.
AB  - BACKGROUND: Statins prevent recurrent ischemic coronary events after acute
      coronary syndrome (ACS) and improve cardiovascular outcome of patients with
      peripheral artery disease. AIM: We sought to evaluate the interrelationship
      between statin use, phenotype of carotid plaques as assessed by ultrasound, and
      outcome of patients with ACS and concomitant carotid disease. METHODS: A total of
      337 consecutive patients with ACS were assessed by coronary angiography and
      Doppler ultrasound of the carotid arteries and followed up for a median period of
      19 months. RESULTS: Carotid plaques were detected in 144 (42%) patients. Of these
      patients, 99 (69%) had echogenic carotid plaques and 45 (31%) had echolucent
      plaques. The groups did not differ significantly with regard to the lipid
      profiles, the prevalence of risk factors, and 1-vessel, 2-vessel, or 3-vessel
      coronary artery disease. During follow-up, 227 (67%) patients were receiving
      statins. We observed 14 cardiac deaths and 17 myocardial infarctions. After
      adjustment for treatment strategy (medical therapy or myocardial
      revascularization), patients with echolucent carotid plaques receiving statin
      therapy (n = 32, 71%) showed a better event-free survival than did patients with
      echolucent plaques not treated with statins (log-rank P = .038). In patients with
      echogenic carotid plaques, the benefit of statin therapy on event-free survival
      was less evident (log-rank P = .56). CONCLUSION: In patients with ACS and
      echolucent carotid plaques, statin therapy is associated with better event-free
      survival, while in patients with ACS and echogenic carotid plaques no clear
      benefit of statins is observed.

PMID- 20043339
TI  - A novel noninvasive ultrasonic cardiac output monitor: comparison with cardiac
      magnetic resonance.
AB  - BACKGROUND: USCOM, a novel continuous wave Doppler (CWD) device, has been
      introduced for noninvasive determination of cardiac output (CO). The present
      study aimed to compare the accuracy and reproducibility of the new device, using
      cardiovascular magnetic resonance imaging (CMR) as the noninvasive gold standard.
      METHODS AND RESULTS: The CO of 56 consecutive patients was prospectively
      determined by CWD either before or after CMR imaging. The CWD probe was placed in
      the suprasternal or supraclavicular notch aiming at the aortic valve. Valid CWD
      signals could be obtained in 45 patients yielding a CO of 5.3+/-1.1 L/min (range,
      3.0-7.5 L/min) by CMR and 4.7+/-1.1 L/min by CWD (2.5-8.0 L/min, P = .004),
      respectively. CWD measurements showed an acceptable agreement with CMR (bias:
      0.6+/-1.1 L/min) and a high reproducibility (bias: 0.1+/-0.4 L/min). Higher CO
      and body mass index (BMI) were identified as sources of inaccuracy in univariate
      analysis. By multivariate analysis, only CO(CMR) was found to be independently
      associated with larger variation. Estimated diameters of the left ventricular
      outflow tract (LVOT), a prerequisite for CO measurement by CWD, correlated only
      weakly with those measured by CMR. CONCLUSIONS: Continuous wave Doppler is a
      feasible technique for measuring cardiac function. Although the overall agreement
      with CMR was acceptable, CWD showed a trend to underestimate CO. The estimated
      LVOT diameter by CWD is likely to be an important source of error. Nevertheless,
      the CWD device could be of clinical use especially for detection of
      intraindividual hemodynamic changes since a high reproducibility could be
      demonstrated.

PMID- 20043340
TI  - Rest myocardial perfusion imaging in a patient with atypical chest pain and a
      nondiagnostic electrocardiogram.
AB  - ACC/AHA guidelines assign a class I indication for use of myocardial perfusion
      imaging (MPI) for the evaluation of chest pain in patients with acute coronary
      syndromes and a nondiagnostic ECG. However, MPI is not a widely used modality for
      the evaluation of patients who present to the ER with chest pain and an
      intermediate pretest probability for coronary artery disease.We report a case in
      which resting MPI was pivotal in diagnosing acute myocardial infarction and
      expedited the appropriate reperfusion strategy.

PMID- 20043341
TI  - Heart rate recovery and tissue Doppler echocardiography in heart failure.
AB  - BACKGROUND: Previous research has demonstrated the prognostic value of
      echocardiography with tissue Doppler imaging (TDI) in the heart failure (HF)
      population. Heart rate recovery (HRR) has also recently shown promise as a
      prognostic marker. HYPOTHESIS: We hypothesize echocardiography with TDI and HRR
      will be significantly correlated and both will provide prognostic information.
      METHODS: A total of 243 subjects underwent echocardiography with TDI and maximal
      exercise testing to determine: (1) the ratio between mitral early (E) to mitral
      annular (E') and E to mitral late (A) velocity; (2) left ventricular ejection
      fraction (LVEF); (3) left ventricular (LV) mass; (4) LV end-systolic volume
      (LVESV); and (5) HRR at 1 minute postexercise (HRR(1)). RESULTS: HRR(1) was
      significantly correlated with LVEF (r = 0.14, P = .03), LV mass (r = - 0.30, P
      <.001), E/A (r = - 0.22, P = .001), and E/E' (r = - 0.49, P <.001). Multivariate
      Cox regression analysis revealed HRR(1) was the strongest predictor of cardiac
      mortality (chi(2): 55.5, P <.001); LV mass (residual chi(2): 13.1, P <.001), E/E'
      (residual chi(2): 11.2, P = .001), and LVESV (residual chi(2): 5.9, P = .015) all
      added significant prognostic value and were retained in the regression while LVEF
      was removed (residual chi(2): 0.008, P = .93). CONCLUSIONS: To our knowledge,
      this is the first investigation demonstrating an association between HRR and
      variables obtained from echocardiography with TDI in subjects with HF. The
      combination of both assessment techniques provides improved prognostic
      discrimination.

PMID- 20043342
TI  - Congenital complete absence of the left pericardium: a rare cause of chest pain
      or pseudo-right heart overload.
AB  - BACKGROUND: Congenital defects of the pericardium are rare and poorly known
      cardiac malformations. Most of them are left-sided and asymptomatic and are
      usually incidentally diagnosed. AIMS: To describe the clinical,
      electrocardiographic, and imaging features of total absence of the left
      pericardium. METHODS AND RESULTS: We report the cases of 3 patients who have been
      seen in our institution with a diagnosis of total congenital absence of the
      pericardium. All of them complained of precordial pain; one of them experienced
      disabling symptoms that justified surgical intervention. All of them had
      previously been suspected to have an atrial septal defect because of the
      echocardiographic appearance of right ventricular volume overload.
      Electrocardiogram, chest x-ray, echocardiography, and magnetic resonance imaging
      of the heart consistently showed remarkably similar features including leftward
      displacement, increased mobility, and interposition of lung tissue between the
      heart and other intrathoracic structures. CONCLUSION: Congenital absence of the
      left pericardium should be known by clinicians as a possible differential
      diagnosis of chest pain or pseudo-right heart overload.

PMID- 20043343
TI  - Native valve Brucella endocarditis.
AB  - OBJECTIVE: Brucellosis is frequently seen in Mediterranean and Middle East
      countries, including Turkey. We report the medical and surgical management of 31
      cases of native endocarditis. MATERIAL AND METHOD: Thirty-one patients were
      admitted to our clinic with suspected Brucella Endocarditis. The diagnosis was
      established by either isolation of Brucella species, or the presence of
      antibodies. Following preoperative antibiotic therapy patients underwent valve
      replacement with excessive tissue debridement. Patients were followed up with
      Brucella titers, blood cultures, and echocardiography. RESULTS: On admission all
      patients were febrile and mostly dyspneic (NYHA Class 3 or 4). The blood tests
      were normal except for elevated ESR, CRP and serological tests. The aortic valve
      was involved in 19 patients, mitral valve in 7 patients, and both valves in 5.
      After serological confirmation of BE, antibiotic therapy was maintained. Twenty
      five of the patients received rifampicine, doxycycline, and cotrimaxozole; 2 of
      them received a combination of rifampicine, streptomycin, and doxycycline; and 4
      of them received rifampicine, tetracycline, and cotrimaxozole. Tissue loss in
      most of the affected leaflets and vegetations were presenting all patients. Valve
      replacements were performed with mechanical and biologic prostheses. All the
      patients were afebrile at discharge but received the antibiotics for 101, 2+/-16,
      9 days. The follow-up was 37, 1+/-9, 2 months. DISCUSSION: In our retrospective
      study, combination of adequate medical and surgical therapy resulted in declined
      morbidity and mortality rate. The valve replacement with aggressive debridement
      is the most important part of the treatment, which should be supported with
      efficient preoperative and long term postoperative medical treatment.

PMID- 20043344
TI  - Sleep disordered breathing is associated with appropriate implantable
      cardioverter defibrillator therapy in congestive heart failure patients.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) are increasingly
      employed in patients affected by congestive heart failure (CHF) and sleep
      disordered breathing (SDB) is frequent in this population. HYPOTHESIS: To
      investigate SDB prevalence and influence on appropriate ICD discharges in CHF
      patients. METHODS: A total of 22 consecutive ICD patients with systolic CHF (left
      ventricular ejection fraction [LVEF]< 45%) were studied by polysomnography.
      RESULTS: A total of 17 (77.2%) showed SDB (apnea-hypopnea index [AHI]_ 10
      events/hour). After controlling for LVEF and New York Heart Association (NYHA)
      class, AHI and severity of hypoxia during sleep results correlated to appropriate
      ICD discharges (r = 0.718; P < .001, r = - 0.619; P = .003, respectively).
      CONCLUSIONS: Sleep disordered breathing is frequent in ICD recipients due to left
      systolic ventricular dysfunction and may increase the risk of ventricular
      arrhythmia and appropriate ICD discharges.

PMID- 20043345
TI  - Fractionated evaluation of immunohistochemical hormone receptor expression
      enhances prognostic prediction in breast cancer patients treated with tamoxifen
      as adjuvant therapy.
AB  - OBJECTIVE: To compare the prognostic prediction between dichotomized and
      fractionated evaluations of hormone receptor expressions. METHODS: Patients with
      stages I-III breast cancers, who received adjuvant tamoxifen, were enrolled. The
      expression of estrogen receptor (ER) and progesterone receptor (PR) was evaluated
      by immunohistochemistry (IHC). A fractionated score (F score), the percentage of
      positive-staining nuclei (0=none, 1=1%-10%, 2=11%-30%, 3=31%-50%, 4=51%-70%, and
      5=71%-100%), was assigned to each case. The dichotomized scoring method defines
      an F score >1 as positive. The prognostic values of both scores were compared by
      multiple Cox's proportional hazard models of disease-free survival (DFS) and
      overall survival (OS). RESULTS: Four hundred and sixteen patients with a median
      follow-up of 78.0 months were included. F scores for ER and PR correlated
      directly with DFS and OS. Although both the dichotomized and fractionated ER and
      PR scores were significantly associated with DFS and OS in univariate analyses,
      only fractionated ER and PR scores remained as independent prognostic factors of
      DFS and OS in the final multiple Cox's proportional hazard models. CONCLUSION:
      Fractionated IHC hormone receptor expression evaluation enhances the prognostic
      prediction compared with a dichotomized assessment.

PMID- 20043346
TI  - Cytocompatibility of regenerated silk fibroin film: a medical biomaterial
      applicable to wound healing.
AB  - OBJECTIVE: To explore the feasibility of using regenerated silk fibroin membrane
      to construct artificial skin substitutes for wound healing, it is necessary to
      evaluate its cytocompatibility. METHODS: The effects of regenerated silk fibroin
      film on cytotoxicity, adhesion, cell cycle, and apoptosis of L929 cells, growth
      and vascular endothelial growth factor (VEGF) expression of ECV304 cells, and
      VEGF, angiopoietin-1 (Ang-1), platelet-derived growth factor (PDGF) and
      fibroblast growth factor 2 (FGF2) expression of WI-38 cells were assessed by 3
      (4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, viable
      cell counting, flow cytometry (FCM), and enzyme-linked immunosorbant assay
      (ELISA). RESULTS: We showed that the regenerated silk fibroin film was not
      cytotoxic to L929 cells and had no adverse influence on their adhesion, cell
      cycle or apoptosis; it had no adverse influence on the growth and VEGF secretion
      of ECV304 cells and no effect on the secretion of VEGF, Ang-1, PDGF and FGF2 by
      WI-38 cells. CONCLUSION: The regenerated silk fibroin film should be an excellent
      biomaterial with good cytocompatibility, providing a framework for reparation
      after trauma in clinical applications.

PMID- 20043347
TI  - Surgical intervention of severe post-ERCP-pancreatitis accompanied with duodenum
      perforation.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure widely used
      to diagnose and treat conditions of biliary or pancreatic ductal system. The post
      ERCP severe acute pancreatitis (SAP) accompanied with duodenum perforation is
      rare but serious, remaining a challenge in clinic. In this study we report two
      such cases. Two Chinese women were treated for clinical suspicion of bile duct
      obstruction and underwent ERCP after admission. Both developed duodenum
      perforation and SAP after ERCP, and were managed in the intensive care unit (ICU)
      and required an organ-failure support. The surgical intervention of the peri
      pancreatic debridement with lumber-abdominal compound incisions and postoperative
      washing and drainage was performed, and the two patients recovered well. The
      therapeutic effect of the peri-pancreatic debridement with lumber-abdominal
      compound incisions combined with postoperative washing and drainage in the
      patients of severe post-ERCP-pancreatitis (PEP) and duodenum perforation is
      satisfactory.

PMID- 20043348
TI  - Pancreatic somatostatinoma with obscure inhibitory syndrome and mixed
      pathological pattern.
AB  - Somatostatinoma is a very rare neuroendocrine tumor that originates from D cells
      and accounts for less than 1% of all gastrointestinal endocrine tumors. The
      duodenum is the most frequent site for this tumor, followed by the pancreas. We
      here describe a 46-year-old Chinese woman who developed pancreatic
      somatostatinoma presenting with the characteristic "inhibitory" syndrome, but the
      symptoms were obscure and seemingly uncorrelated. This case is also unique for
      its large tumor size and mixed pathological pattern. Distal pancreatectomy was
      performed, and the patient has remained well since operation. As the syndromes of
      somatostatinoma may be obscure and atypical, clinicians should review all
      clinical findings to obtain an accurate diagnosis. Aggressive surgery is
      preferred to improve the survival.

PMID- 20043349
TI  - Quantification of Helicobacter pylori levels in soil samples from public
      playgrounds in Spain.
AB  - Helicobacter pylori are ubiquitous Gram-negative bacteria with a high estimated
      level of infection in the world populations, but a majority of the infected
      persons are asymptomatic. This pathogen has been classified by the World Health
      Organization as a class I carcinogen and recognized as the causal agent of most
      peptic ulcers and chronic gastritis that might lead to stomach cancer. Although
      not all the transmission pathways of these bacteria into humans have been
      properly identified, enough data have suggested that the oral-oral or fecal-oral
      ones are the main infection routes. Helicobacter pylori have been detected in non
      treated water and in drinking water, which suggested that water might be an
      important infection source. As childhood is the critical period of infection, the
      aim of the present work was to examine the presence of Helicobacter pylori in
      soil samples from public playing areas of Spanish parks.

PMID- 20043350
TI  - Viral infection of tobacco plants improves performance of Bemisia tabaci but more
      so for an invasive than for an indigenous biotype of the whitefly.
AB  - The ecological effects of plant-virus-vector interactions on invasion of alien
      plant viral vectors have been rarely investigated. We examined the transmission
      of Tomato yellow leaf curl China virus (TYLCCNV) by the invasive Q biotype and
      the indigenous ZHJ2 biotype of the whitefly Bemisia tabaci, a plant viral vector,
      as well as the influence of TYLCCNV-infection of plants on the performance of the
      two whitefly biotypes. Both whitefly biotypes were able to acquire viruses from
      infected plants and retained them in their bodies, but were unable to transmit
      them to either tobacco or tomato plants. However, when the Q biotype fed on
      tobacco plants infected with TYLCCNV, its fecundity and longevity were increased
      by 7- and 1-fold, respectively, compared to those of the Q biotype fed on
      uninfected tobacco plants. When the ZHJ2 biotype fed on virus-infected plants,
      its fecundity and longevity were increased by only 2- and 0.5-fold, respectively.
      These data show that the Q biotype acquired higher beneficial effects from
      TYLCCNV-infection of tobacco plants than the ZHJ2 biotype. Thus, the Q biotype
      whitefly may have advantages in its invasion and displacement of the indigenous
      ZHJ2 biotype.

PMID- 20043351
TI  - A food-grade industrial arming yeast expressing beta-1,3-1,4-glucanase with
      enhanced thermal stability.
AB  - The aim of this work was to construct a novel food-grade industrial arming yeast
      displaying beta-1,3-1,4-glucanase and to evaluate the thermal stability of the
      glucanase for practical application. For this purpose, a bi-directional vector
      containing galactokinase (GAL1) and phosphoglycerate kinase 1 (PGK1) promoters in
      different orientations was constructed. The beta-1,3-1,4-glucanase gene from
      Bacillus subtilis was fused to alpha-agglutinin and expressed under the control
      of the GAL1 promoter. alpha-galactosidase induced by the constitutive PGK1
      promoter was used as a food-grade selection marker. The feasibility of the alpha
      galactosidase marker was confirmed by the growth of transformants harboring the
      constructed vector on a medium containing melibiose as a sole carbon source, and
      by the clear halo around the transformants in Congo-red plates owing to the
      expression of beta-1,3-1,4-glucanase. The analysis of beta-1,3-1,4-glucanase
      activity in cell pellets and in the supernatant of the recombinant yeast strain
      revealed that beta-1,3-1,4-glucanase was successfully displayed on the cell
      surface of the yeast. The displayed beta-1,3-1,4-glucanase activity in the
      recombinant yeast cells increased immediately after the addition of galactose and
      reached 45.1 U/ml after 32-h induction. The thermal stability of beta-1,3-1,4
      glucanase displayed in the recombinant yeast cells was enhanced compared with the
      free enzyme. These results suggest that the constructed food-grade yeast has the
      potential to improve the brewing properties of beer.

PMID- 20043352
TI  - Monoclonal antibody-based ELISA and colloidal gold-based immunochromatographic
      assay for streptomycin residue detection in milk and swine urine.
AB  - A protein conjugate of streptomycin (streptomycin-bovine serum albumin (BSA)
      conjugate) was prepared and used as immunogen to produce monoclonal antibodies
      (MAb). One hybridoma secreting anti-streptomycin MAb was obtained and then used
      to produce MAb. The MAb named 13H5 showed the 50% maximal inhibitory
      concentration (IC(50)) value of 4.65 ng/ml and the IC(20) value of 0.21 ng/ml in
      phosphate buffered saline (PBS). At optimum conditions, an indirect competitive
      enzyme-linked immunosorbent assay (ELISA) and a colloidal gold-based
      immunochromatographic assay (CGIA) were developed and applied to detect
      streptomycin residues in milk and swine urine samples. The developed ELISA showed
      that the minimum detection limit was 2.0 and 1.9 ng/ml for milk and swine urine
      samples, respectively, without obvious cross-reactivity to other tested
      antibiotics except dihydrostreptomycin which gave a 118.32% cross reaction value.
      Milk and swine urine samples spiked with streptomycin at 10, 50, 100 and 200
      ng/ml were analyzed by the established ELISA. The mean recovery of streptomycin
      was from 81.9% to 105.5% and from 84.3% to 92.2% for milk and swine urine,
      respectively. The optimized CGIA showed that the minimum detection limit was 20.0
      ng/ml for milk and swine urine samples. The results of spiked analysis and
      specific analysis demonstrate that the CGIA could be applicable for screening
      milk and swine urine samples for the presence of streptomycin residues on-site.
      The established ELISA and CGIA allow the rapid, low-cost, and sensitive
      determination of streptomycin residues in food samples.

PMID- 20043353
TI  - Identification of Colletotrichum spp. isolated from strawberry in Zhejiang
      Province and Shanghai City, China.
AB  - Strawberry anthracnose, caused by Colletotrichum spp., is a major disease of
      cultivated strawberry. This study identifies 31 isolates of Colletotrichum spp.
      which cause strawberry anthracnose in Zhejiang Province and Shanghai City, China.
      Eleven isolates were identified as C. acutatum, 10 as C. gloeosporioides and 10
      as C. fragariae based on morphological characteristics, phylogenetic and sequence
      analyses. Species-specific polymerase chain reaction (PCR) and enzyme digestion
      further confirmed the identification of the Colletotrichum spp., demonstrating
      that these three species are currently the causal agents of strawberry
      anthracnose in the studied regions. Based on analysis of rDNA internal
      transcribed spacers (ITS) sequences, sequences of all C. acutatum were identical,
      and little genetic variability was observed between C. fragariae and C.
      gloeosporioides. However, the conservative nature of the MvnI specific site from
      isolates of C. gloeosporioides was confirmed, and this site could be used to
      differentiate C. gloeosporioides from C. fragariae.

PMID- 20043354
TI  - Discrimination of rice panicles by hyperspectral reflectance data based on
      principal component analysis and support vector classification.
AB  - Detection of crop health conditions plays an important role in making control
      strategies of crop disease and insect damage and gaining high-quality production
      at late growth stages. In this study, hyperspectral reflectance of rice panicles
      was measured at the visible and near-infrared regions. The panicles were divided
      into three groups according to health conditions: healthy panicles, empty
      panicles caused by Nilaparvata lugens Stal, and panicles infected with
      Ustilaginoidea virens. Low order derivative spectra, namely, the first and second
      orders, were obtained using different techniques. Principal component analysis
      (PCA) was performed to obtain the principal component spectra (PCS) of the
      foregoing derivative and raw spectra to reduce the reflectance spectral
      dimension. Support vector classification (SVC) was employed to discriminate the
      healthy, empty, and infected panicles, with the front three PCS as the
      independent variables. The overall accuracy and kappa coefficient were used to
      assess the classification accuracy of SVC. The overall accuracies of SVC with PCS
      derived from the raw, first, and second reflectance spectra for the testing
      dataset were 96.55%, 99.14%, and 96.55%, and the kappa coefficients were 94.81%,
      98.71%, and 94.82%, respectively. Our results demonstrated that it is feasible to
      use visible and near-infrared spectroscopy to discriminate health conditions of
      rice panicles.

PMID- 20043355
TI  - Dreaming and cinematographic consciousness.

PMID- 20043356
TI  - Gluttony and power in Iurii Olesha's "Envy".

PMID- 20043357
TI  - Practice improvement in cervical screening and management (PICSM): symposium on
      management of cervical abnormalities in adolescents and young women.

PMID- 20043358
TI  - [The administration of military households and their disputes over military
      service in the Jiangxi guards and battalions during the Ming and Qing periods].

PMID- 20043359
TI  - [Desire and the body in 18th-century Chinese society: carnival beyond "civil"
      society].

PMID- 20043360
TI  - Retracted surgical forum abstracts.

PMID- 20043361
TI  - [Political science and history: Eduardo Cruz-Coke and the welfare state in Chile,
      1937-38].

PMID- 20043363
TI  - Building on today's standard of care. Abstracts of the 1st European Gaucher
      Leadership Forum. Milan, Italy. May 14-15, 2009.

PMID- 20043362
TI  - [Sports in black Africa: developing research into sports institutions, practices,
      and facilities].

PMID- 20043364
TI  - [Where are Rwandans living today? Rupture, reconstruction, and continuity in the
      distribution of population since 1994].

PMID- 20043365
TI  - "Playing at public health": the search for control in South Durban, 1860-1932.

PMID- 20043366
TI  - Implants and endodontics: from facts and myths to beneficial synergisms.
AB  - Osseointegrated implants have affected the decision-making process for
      prosthodontic, periodontic, and endodontic treatment planning. As a result, the
      traditional endodontic care model has undergone a paradigm shift. As with any
      emerging technology, there is concern that the initial enthusiasm surrounding
      implants could supersede quality of patient care issues, especially since there
      is no consensus about whether it is better to restore or replace a compromised
      tooth. The results of a number of meta-analyses show no statistical difference in
      terms of the long-term outcomes for single -tooth implants and endodontically
      treated teeth. Obviously, the decision to treat a tooth endodontically or replace
      it with a single-tooth implant should be based on other criteria. This article
      compares how certain variables affect the outcome of cases in which teeth are
      treated using either root canal treatment or single-tooth implants and explores
      the beneficial synergistic relationship between these two viable alternatives.

PMID- 20043367
TI  - Making the H1N1 (Swine) flu vaccine mandatory for hospital employees.

PMID- 20043368
TI  - One person's food: how and why fish avoidance may affect the settlement and
      subsistence patterns of hunter-gatherers.

PMID- 20043369
TI  - An integrative approach to mortuary analysis: social and symbolic dimensions of
      Chumash burial practices.
AB  - Although most archaeologists recognize that valuable information about the social
      lives of ancient people can be obtained through the study of burial practices, it
      is clear that the symbolic nature of burial rituals makes interpreting their
      social significance a hazardous enterprise. These analytical difficulties can be
      greatly reduced using a research strategy that draws upon the strengths of a
      broad range of conceptually and methodologically independent data sources. We
      illustrate this approach by using archaeological data from cemeteries at Malibu,
      California, to explore an issue over which researchers are sharply divided: when
      did the simple chiefdoms of the Chumash Indians first appear in the Santa Barbara
      Channel area? First we establish the social correlates of Chumash burial
      practices through the comparison of historic-period cemetery data, ethnohistoric
      records, and ethnographic accounts. The resulting understanding of mortuary
      symbolism is then used to generate hypotheses about the social significance of
      prehistoric-period Malibu burial patterns. Finally, bioarchaeological data on
      genetic relationships, health status, and activity are used to independently test
      artifact-based hypotheses about prehistoric Chumash social organization.
      Together, these independent data sources constitute strong evidence for the
      existence of a ranked society with a hereditary elite during the late Middle
      period in the Santa Barbara Channel area.

PMID- 20043370
TI  - A zooarchaeological signature for meat storage: re-thinking the drying utility
      index.
AB  - Although the practice of food storage is important to many questions addressed by
      archaeologists, demonstrating its presence in archaeological contexts can be
      difficult or impossible. One potentially useful approach to meat storage is the
      concept of the Drying Utility Index, introduced by Lewis Binford (1978) to
      predict which carcass portions, with attached bone, will be selected for storage
      by drying. However, this index has not been widely used by zooarchaeologists, at
      least in part because the calculations involved in its derivation are extremely
      complex. This paper presents a new, simplified index, the Meat Drying Index,
      which is easier to calculate and more transparent than the Drying Utility Index,
      yet which retains all of its key attributes. This new index is applied to caribou
      bone samples from two regions: Binford's (1978) Nunamiut data from northern
      Alaska, and the contents of three caches from the Barren Grounds of Canada, near
      Baker Lake, Nunavut. In both cases, the Meat Drying Index correlates with the
      observed element frequencies as well as, or better than, the original Drying
      Utility Index. As a result, the new index may prove applicable to element
      distributions from a wide range of archaeological contexts in which storage of
      meat by drying is suspected.

PMID- 20043371
TI  - Estimating the minimum number of skeletal elements (MNE) in zooarchaeology: a
      review and a new image-analysis GIS approach.
AB  - Most zooarchaeologists employ some type of derived measure of skeletal element
      abundance in their analyses of faunal data. The minimum number of individuals
      (MNI) and the minimum number of animal units (MAU) are two of the most popular
      derived measurements, and each is based on a prior estimate of the minimum number
      of elements (MNE). Thus, the estimate of MNE from fragmented faunal fragments is
      the essential foundation for all inferences emanating from MNI and MAU estimates
      of skeletal element abundance. Estimating the MNE represented by a sample of
      faunal fragments is a complicated procedure that involves various assumptions,
      possible mathematical manipulations, and subjectivity. Unfortunately, the
      reasoning and methods underlying this procedure are unstandardized in
      zooarchaeology, and even worse, rarely made explicit. We review the scarce
      literature on this topic and identify two different approaches: the fraction
      summation approach and the overlap approach. We identify strengths and weaknesses
      in both approaches. We then present a new method that is based on using image
      analysis GIS software to count overlapping fragments that have been converted to
      pixel images. This method maintains the strengths of the other methods while
      overcoming most of their weaknesses. It promises numerous powerful analytical
      capabilities that go far beyond the routines available in spreadsheets and
      databases. It also offers nearly boundless flexibility in database recoding and
      extremely complete information storage. Perhaps its greatest strength is that it
      is based on very intuitive reasoning.

PMID- 20043372
TI  - How many frogs does it take to leap around the Americas? Comments on Anderson and
      Gillam.
AB  - In modeling the colonization of the Americas, Anderson and Gillam (2000) employ
      size estimates for vanguard forager bands that are of dubious reproductive
      viability in light of human incest prohibitions and variable sex ratios at birth.

PMID- 20043373
TI  - Paleoindian interaction and mating networks: reply to Moore and Moseley.
AB  - How early human populations in North America maintained reproductive viability is
      a question that has shaped our research for over a decade. The concept of staging
      areas, mechanisms for band-macroband interaction, and an examination of how
      interaction networks could have formed and evolved over the course of the
      Paleoindian era are all solutions that we have presented.

PMID- 20043374
TI  - Archaeological politics and public interest in paleoamerican studies: lessons
      from Gordon Creek Woman and Kennewick Man.
AB  - This paper discusses the Kennewick lawsuit as it relates to the intended purposes
      of NAGPRA. It also reflects upon comments made by Swedlund and Anderson (1999) in
      a recent American Antiquity Forum, which conceptually linked two ancient
      skeletons, Gordon Creek Woman and Kennewick Man. Their assertions indicate the
      need for clarifying specific issues and events pertaining to the case. We comment
      on how times have changed with the passage of NAGPRA, how differently these two
      skeletons have been treated by the media and the scientists interested in them,
      and show how discussions of biological affiliation have relevance. There is still
      much to be learned from Kennewick Man and Gordon Creek Woman. But attempts to
      bring the concept of race or racial typing into the picture show misunderstanding
      regarding the use of morphological data in tracing population historical
      relationships, not to mention obfuscating the scientific issues they raise.

PMID- 20043375
TI  - Paleocoastal marine fishing on the Pacific Coast of the Americas: perspectives
      from Daisy Cave, California.
AB  - Analysis of over 27,000 fish bones from strata at Daisy Cave dated between about
      11,500 and 8500 cal B.P. suggests that early Channel Islanders fished relatively
      intensively in a variety of habitats using a number of distinct technologies,
      including boats and the earliest evidence for hook-and-line fishing on the
      Pacific Coast of the Americas. The abundance of fish remains and fishing-related
      artifacts supports dietary reconstructions that suggest fish provided more than
      50 percent of the edible meat represented in faunal samples from the early
      Holocene site strata. The abundance and economic importance of fish at Daisy
      Cave, unprecedented among early sites along the Pacific Coast of North America,
      suggest that early maritime capabilities on the Channel Islands were both more
      advanced and more variable than previously believed. When combined with a survey
      of fish remains from several other early Pacific Coast sites, these data suggest
      that early New World peoples effectively used watercraft, captured a diverse
      array of fish, and exploited a variety of marine habitats and resources.

PMID- 20043376
TI  - Grief and burial in the American Southwest: the role of evolutionary theory in
      the interpretation of mortuary remains.
AB  - Evolutionary theory, in consort with Marxism and processualism, provides new
      insights into the interpretation of grave-good variation. Processual
      interpretations of burial sites in the American Southwest cite age, sex, or
      social rank as the main determinants of burial-good variation. Marxist theorists
      suggest that mortuary ritual mediates social tension between an egalitarian
      mindset and an existing social inequality. Evolutionary theory provides a
      supplementary explanatory framework. Recent studies guided by kin-selection
      theory suggest that humans grieve more for individuals of high reproductive value
      and genetic relatedness. Ethnographic examples also show that individuals mourn
      more intensively and, thus, place more social emphasis on burials of individuals
      of highest reproductive value (young adults). Analysis of grave goods from La
      Ciudad, a Hohokam site in the American Southwest, supports the hypothesis that
      labor value, reproductive value, and grief contributed to grave-good
      differentiation. At La Ciudad, individuals between the ages of 10 and 20
      possessed more and higher-quality grave goods on average than any other age
      group. Grief at the loss of a young adult of high reproductive and labor value
      may facilitate explanation of mortuary variation at La Ciudad, as well as other
      sites in the greater Southwest and beyond.

PMID- 20043377
TI  - Invited Commentary. Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy with severe factor XII deficiency.

PMID- 20043378
TI  - New world data.

PMID- 20043380
TI  - [38-year-old athlete. Stabbing pain in the calf during training].

PMID- 20043379
TI  - Role of epidermal growth factor receptor in ovine fetal pulmonary vascular
      remodeling following exposure to high altitude long-term hypoxia.
AB  - High altitude long-term hypoxia (LTH) in the fetus may result in pulmonary
      vascular smooth muscle cell (PVSMC) proliferation and pulmonary vascular
      remodeling. Our objective was to determine if epidermal growth factor receptor
      (EGFR) is involved in hypoxia induced PVSMC proliferation or in pulmonary
      vascular remodeling in ovine fetuses exposed to high altitude LTH. Fetuses of
      pregnant ewes that were held at 3820-m altitude from *30 to 140 days (LTH)
      gestation and sea level control pregnant ewes were delivered near term.
      Morphometric analyses and immunohistochemistry were done on fetal lung sections.
      Pulmonary arteries of LTH fetuses exhibited medial wall thickening and distal
      muscularization. Western blot analyses done on protein isolated from pulmonary
      arteries demonstrated an upregulation of EGFR. This upregulation was attributed
      in part to PVSMC in the medial wall by immunohistochemistry.Proliferation of
      fetal ovine PVSMC after 24 h of hypoxia (2% O2) was attenuated by inhibition of
      EGFR with 250 nmol tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline
      (AG1478), a specific EGFR protein tyrosine kinase inhibitor, when measured by
      [3H]-thymidine incorporation. Our data indicate that EGFR plays a role in fetal
      ovine pulmonary vascular remodeling following long-term fetal hypoxia and that
      inhibition of EGFR signaling may ameliorate hypoxia-induced pulmonary vascular
      remodeling.

PMID- 20043381
TI  - [Underestimated tiny particles. How dangerous are nanoparticles? (interview by
      Dr. Thomas Meissner)].

PMID- 20043382
TI  - [Patient with phlegmasia coerulea dolens. No compression bandage was applied?].

PMID- 20043383
TI  - [Family physician centered model of AOK. Higher fees, fewer administration
      costs].

PMID- 20043384
TI  - [H1N1 vaccination and therapy. Document expenditures!]].

PMID- 20043385
TI  - [Controversies in therapy of diverticulosis. When refer to a surgeon?].

PMID- 20043386
TI  - [Difficult differential diagnosis. Appendicitis or right quadrant
      diverticulitis?].

PMID- 20043387
TI  - [Hypertensive emergency in a 65-year-old patient. Noncompliance in taking
      antihypertensive drugs].

PMID- 20043388
TI  - [Vaccines, molecular scissors, fusion inhibitors. What does HIV therapy of the
      future look like?].

PMID- 20043389
TI  - [Well protected on vacation. East of the Oder and south of Alps threaten
      hepatitis A and polio].

PMID- 20043390
TI  - [Mistletoe therapy in cancer treatment: pros and cons].

PMID- 20043391
TI  - [New treatment strategies for the management of hypertension].

PMID- 20043392
TI  - [Acute ischemia of the extremities].

PMID- 20043393
TI  - [Differential diagnosis of plantar dermatosis].

PMID- 20043394
TI  - [Back pain in adolescents].

PMID- 20043395
TI  - [Big gaps in coronary heart disease prevention. Statins are not enough in
      dyslipidemia].

PMID- 20043396
TI  - [It can't be more compatible. Omega-3 fatty acids in addition to statin provide
      optimal lipid management].

PMID- 20043397
TI  - Investigational use of metomidate hydrochloride as a shipping additive for two
      ornamental fishes.
AB  - During shipping, ornamental fish can be stressed due to handling, high stocking
      densities, and deteriorating water quality. Adding sedatives, such as metomidate
      hydrochloride, to shipping water may improve fish survival rates and the
      percentage of fish in saleable condition. Although the effects of metomidate
      hydrochloride on the stress response in fish have been studied, its application
      as a shipping additive has not been well investigated, particularly for tropical
      ornamental fishes shipped under industry conditions. Convict cichlids Cichlasoma
      nigrofasciatum and black mollies Poecilia sphenops were evaluated for 7 d after a
      24-h period of exposure (including ground and air transport) to one of four
      metomidate hydrochloride concentrations: 0.0, 0.2, 0.5, and 1.0 mg/L. Immediate
      posttransport and cumulative mortality data, as well as 12-h and 7-d
      posttransport appearance and behavior scores, were generated. In convict
      cichlids, the highest dose of metomidate hydrochloride (1.0 mg/L) reduced
      mortality (0% compared with cumulative means of 5.5-9.2% in other groups) and
      increased the percentage of saleable fish (91.7% were immediately saleable
      compared with 12.5-50% in other groups). No effect was detected in black mollies
      at any concentration tested. Metomidate hydrochloride showed promise as a
      shipping additive for convict cichlids, but further studies are warranted to
      evaluate species-specific responses in other ornamental species.

PMID- 20043398
TI  - Attenuation of the fish pathogen Francisella sp. by mutation of the iglC* gene.
AB  - Fish francisellosis is an emergent disease caused by gram-negative facultative
      intracellular bacteria of the genus Francisella. Different strains of the
      bacterium have caused high mortalities in warmwater and coldwater fish species.
      Francisella sp. isolates from fish have been found to share more than 97%
      identity to the human pathogen Francisella tularensis upon 16S ribosomal RNA
      sequence comparison. Homologue genes of the F. tularensis intracellular growth
      locus (iglA*, iglB*, iglC*, and iglD*) were identified from LADL 07-285A, a
      clinical isolate obtained from diseased Nile tilapia Oreochromis niloticus. The
      iglABCD operon DNA sequence comparison revealed that Francisella LADL 07-285A had
      94% identity with F. philomiragia subsp. philomiragia and 83% identity with F.
      tularensis subsp. novicida U112. The functions of the conserved proteins
      corresponding to the genes are elusive but appear to be essential for the ability
      of Francisella sp. to survive within macrophages and cause disease. An insertion
      mutation was made in the iglC* gene of LADL 07-285A by allelic exchange, and the
      iglC* mutant was found to be attenuated after intraperitoneal and immersion
      challenges in Nile tilapia. Laboratory challenge methods for inducing
      francisellosis in Nile tilapia were evaluated by intraperitoneal injection and
      immersion with serial dilutions of Francisella LADL 07-285A. The dose lethal to
      50% of test fish at 40 d postchallenge was 10(-5.3) (about 1.2 X 10(3) colony
      forming units/fish) by intraperitoneal injection and was 10(-1) (2.3 X 10(7)
      colony-forming units/mL of tank water) by immersion.

PMID- 20043399
TI  - Identification of Vibrio harveyi isolated from diseased Asian seabass Lates
      calcarifer by use of 16S ribosomal DNA sequencing.
AB  - The grow out of Asian seabass Lates calcarifer in marine net-cages is a popular
      aquaculture activity in Malaysia. Production of this species is greatly affected
      by the occurrence of vibriosis, which causes heavy mortality. Generally, young
      fish are more susceptible; they exhibit anorexia and skin darkening, followed by
      heavy mortality. The acutely affected older fish may also exhibit bloody lesions
      around the anus and the base of the fins. Twenty-one bacterial isolates obtained
      from internal organs (kidney, heart, spleen and liver) of the affected specimens
      were subjected to phenotypic characterization, testing for antibiotic
      susceptibility, and 16S ribosomal DNA sequencing. The sequencing result showed
      that all of the bacterial isolates belonged to Vibrio harveyi. The phenotypic
      characterization, however, identified 4 of the bacterial isolates as V. harveyi,
      16 as V. parahaemolyticus, and 1 as V. alginolyticus. These findings suggest that
      biochemical features alone cannot be reliably used to identify bacterial
      pathogens, including V. harveyi, in aquaculture. Antibiotic susceptibility assays
      showed that some antibiotics, including oxytetracycline, nitrofurantoin,
      furazolidone, streptomycin, sulfamethoxazole, chloramphenicol, nalidixic acid,
      and oxolinic acid were effective against V. harveyi. Considering the side effects
      of these antibiotics, however, their use is not recommended in the aquaculture of
      Asian seabass.

PMID- 20043400
TI  - Evaluation of dairy-yeast prebiotic supplementation in the diet of juvenile
      goldfish in the presence or absence of phytoplankton and zooplankton.
AB  - Prebiotics recently have been shown to increase immune responses and disease
      resistance in certain fish species; therefore, the current study was conducted to
      evaluate the commercially available dairy-yeast prebiotic, GroBiotic-A, for use
      with juvenile goldfish Carassius auratus. The study consisted of two 10-week
      feeding trials in which juvenile goldfish were fed practical diets that were
      either unsupplemented or supplemented with the dairy-yeast prebiotic at 2% by dry
      weight. Juvenile fish were sorted by size and stocked into 12 units within each
      of two culture systems: one indoor system supplied with recirculated well water
      and one system located outdoors with a continuous flow of pond water to provide a
      source of phytoplankton and zooplankton. Both diets were fed to fish in six units
      within each system at the same fixed percentage of body weight twice daily.
      Culture system (i.e., presence or absence of phytoplankton and zooplankton) was
      the primary factor influencing (P < 0.0001) percent weight gain, feed efficiency,
      and survival of goldfish during the feeding trials. No dietary effect was
      detected, although there was a significant (P < 0.05) interaction between culture
      system and diet, with supplementation of the dairy-yeast prebiotic tending to
      improve weight gain and feed efficiency of fish in the presence of
      phytoplankton/zooplankton. During a controlled disease challenge with an
      intraperitoneally administered dose of Aeromonas hydrophila that was equivalent
      to a predetermined LD50 (dose lethal to 50% of test fish), average survival
      values ranged between 67% and 83% for fish that previously had access to
      phytoplankton/zooplankton compared with 17-33% for fish that had no access to
      phytoplankton/zooplankton. The dairy-yeast prebiotic, however, did not enhance
      resistance of goldfish to the bacterial pathogen and did not greatly alter
      microbiota of the anterior or posterior gastrointestinal tract based on
      denaturing gradient gel electrophoresis analysis. In conclusion, the dairy-yeast
      prebiotic did not improve feed efficiency in goldfish or resistance to a
      bacterial pathogen as previously observed in golden shiners Notemigonus
      crysoleucas and hybrid bass (white bass Morone chrysops X striped bass M.
      saxatilis).

PMID- 20043401
TI  - Occurrence of Glugea pimephales in planktonic larvae of fathead minnow in
      Algonquin Park, Ontario.
AB  - The microsporidian Glugea pimephales was found parasitizing larval fathead minnow
      Pimephales promelas in Scott Lake, Algonquin Park, Ontario. These fish were
      estimated to be 2-3 weeks posthatch and, given the development time of the
      parasite, must have acquired infection soon after commencement of exogenous
      feeding. Histological sections revealed that the parasite typically developed in
      loose connective tissue between the peritoneum and the dermis of the abdominal
      cavity, with protruding xenomas of up to 2.6 mm in diameter forming near the
      vent. Prevalence was estimated at 1% by divers performing snorkel surveys along
      the lake shoreline. Divers following schools of fathead minnow consistently
      reported that larvae with the obvious cysts wobbled during swimming and that
      infected fish were typically located at the back of the dispersing school. This
      case history joins a growing list of studies suggesting that fish can become
      infected with parasites soon after hatch, the potential importance of which has
      not been critically studied.

PMID- 20043402
TI  - Development and validation of a short-time cell culture and multiplex reverse
      transcriptase polymerase chain reaction assay for infectious pancreatic necrosis
      virus in Mexican farm-sampled rainbow trout.
AB  - The infectious pancreatic necrosis virus (IPNV) affects several species of
      freshwater and marine fish. In Mexico, IPNV has an important impact on farming of
      rainbow trout Oncorhynchus mykiss; however, IPNV distribution in Mexico is
      unclear. The diagnosis of IPNV is laborious; usually it is based on isolation
      tests in cell culture followed by immunological identification using techniques
      of serum neutralization, immunofluorescence, or enzyme-linked immunosorbent
      assay. It has recently been demonstrated that reverse transcriptase polymerase
      chain reaction (RT-PCR) is an adequate method for the detection of aquatic
      birnaviruses. However, its diagnostic use is still limited because very low
      titers of viable virus cannot be easily detected. In this study, a combination of
      short-time cell culture and multiplex RT-PCR was established for the diagnosis of
      IPNV in rainbow trout obtained from farms in the state of Mexico. Three primer
      sets were used in a single reaction in the multiplex RT-PCR to increase the
      probability of identifying all serotypes of IPNV serogroup A as well as to help
      prevent a false-negative result. This approach was able to identify samples with
      an IPNV concentration of just 0.01 tissue culture infective dose with 50%
      endpoint (TCID50)/mL, and it identified more infected fish than RT-PCR alone or
      first-passage cell culture alone. Moreover, this technique made the same
      identifications as second-passage cell culture but in approximately 30% of the
      time needed for second-passage cell culture. Consequently, the time and cost
      efficiency of IPNV diagnosis were greatly reduced.

PMID- 20043403
TI  - Studies on the possibility of vertical transmission of Norwegian salmonid
      Alphavirus in production of Atlantic salmon in Norway.
AB  - Disease associated with salmonid Alphavirus (SAV) infection is a significant
      problem for farm production of salmonids in Europe. The SAV subtype 3 (SAV3) is a
      Norwegian subtype present exclusively in production systems for Atlantic salmon
      Salmo salar and rainbow trout Oncorhynchus mykiss in western Norway. It has been
      suggested that SAV3 is transmitted through smolt transport from the main area for
      SAV disease in western Norway to as far as northern Norway. One explanation for
      this type of spread is that SAV is present at freshwater production sites for
      Atlantic salmon smolts. The present study confirms this, showing that SAV3 is
      present at smolt production sites in Norway. At two sites in northern Norway that
      had received eggs from broodfish companies in Hordaland County, western Norway, 2
      4-g fry were positive for SAV3. Hence, it cannot be excluded that vertical
      transmission could have contributed to the presence of SAV3 in northern Norway.
      In the present study, we followed the normal production cycle for Atlantic salmon
      in a fish farming company in Hordaland County. Twelve of 353 broodfish in study 1
      and 28 of 31 broodfish in study 2 were found to be carriers of SAV3. In the same
      two studies, SAV was also detected in eggs (1 of 220), eyed eggs (3 of 270), and
      fry (6 of 600). The SAV was not detected in parr, smolts, or postsmolts, but
      after a year at sea the fish developed SAV disease. Given the difficulties in
      tracing the virus through the production cycle until development of SAV disease
      in the marine farm, we cannot draw any firm conclusions about whether vertical
      transmission occurs in Norwegian salmon production, and we cannot exclude the
      possibility that the development of SAV after 1 year at sea was caused by
      horizontal transmission rather than vertical transmission.

PMID- 20043404
TI  - Expanded range and new host species of Mycobacterium shottsii and M.
      pseudoshottsii.
AB  - Mycobacterium shottsii and M. pseudoshottsii are recently described mycobacteria
      commonly isolated from Chesapeake Bay striped bass Morone saxatilis. However,
      their distribution in striped bass outside of the Chesapeake region and their
      ability to infect alternative hosts have not been described. Mycobacteria
      identified as M. shottsii (based on fatty acid methyl ester analysis and
      multigene sequencing) were isolated from striped bass collected in Albemarle
      Sound, North Carolina, and white perch Morone americana in the Rhode River,
      Maryland, and detected in striped bass from the New York Bight off Long Island,
      New York. Mycobacterium pseudoshottsii were isolated from white perch in the
      Rhode and Corsica rivers, Maryland, and detected in striped bass in the New York
      Bight. This work demonstrates that these mycobacteria can be found outside of the
      Chesapeake Bay as well as in hosts other than striped bass.

PMID- 20043405
TI  - Pathogenicity of Streptococcus ictaluri to channel catfish.
AB  - The pathogenicity of a Streptococcus ictaluri isolate in channel catfish
      Ictalurus punctatus at the fry (0.5 g), fingerling (15 g), and juvenile (55 g)
      stages was determined by experimental bath immersion and injection experiments.
      Channel catfish were exposed in 1-L immersion baths containing 10(8), 10(9),
      10(10), 10(11) or 10(12) colony-forming units (cfu) of S. ictaluri. Fish were
      also injected intraperitoneally with 0.1 mL of bacterial solution for final doses
      of 10(4), 10(5), 10(6), 10(7), or 10(8) cfu of S. ictaluri per fish.
      Streptococcus ictaluri caused mortality in fry, fingerling, and juvenile channel
      catfish within 21 d postinfection. When mortalities were calculated based on size
      and challenge route, the cumulative percent mortalities were 11% for fry and 0%
      for fingerlings by the bath immersion route and 14% for fingerlings and 6% for
      juveniles by the injection route. Isolation of S. ictaluri from moribund and dead
      catfish was confirmed by the newly established BIOLOG profile (MicroLog3 system).
      The results indicate that channel catfish were only susceptible to high
      concentrations of S. ictaluri and that juvenile channel catfish were less
      susceptible, possibly explaining why little mortality has been attributed to S.
      ictaluri infection in catfish aquaculture.

PMID- 20043406
TI  - Outbreaks of Ichthyophthirius multifiliis in redtail barbs Barbus haasi in a
      Mediterranean stream during drought.
AB  - In 2008, inland waterways in Catalonia (northeast Iberian Peninsula, Spain)
      experienced one of the worst droughts recorded in this region in recent decades.
      During this period, an epizootic of Ichthyophthirius multifiliis was detected for
      the first time in a Mediterranean stream, with 21% prevalence in a population of
      redtail barbs Barbus haasi. Environmental features and the fish population in
      this stream were compared during 2007-2009. Fish density and the average fish
      size were reduced significantly after the outbreak of I. multifiliis in this
      population. During 2008, parasitized fish were significantly larger than
      nonparasitized fish. In addition, a significant, positive correlation was found
      between parasite load and fish size. The origin of I. multifiliis is unknown, but
      an introduced species detected in April 2007 may have carried it. The combination
      of stress to the redtail barbs due to suboptimal conditions and favorable
      environmental conditions for parasite multiplication (e.g., suitable water
      temperature and low water flow) could have enhanced fish susceptibility to the
      parasite in April 2008. Further studies are needed to establish the incidence of
      freshwater fish diseases in Mediterranean watersheds, and water management
      policies should be reviewed to improve the conservation of native fish fauna.

PMID- 20043407
TI  - Flow cytometric characterization of freshwater crayfish hemocytes for the
      examination of physiological status in wild and captive animals.
AB  - Enumeration of invertebrate hemocytes is a potentially powerful tool for the
      determination of physiological effects of extrinsic stressors, such as hypoxia,
      disease, and toxicant exposure. A detailed flow cytometric method of broad
      application was developed for the objective characterization and enumeration of
      the hemocytes of New Zealand freshwater crayfish Paranephrops planifrons for the
      purpose of physiological health assessment. Hemocyte populations were isolated by
      flow cytometric sorting based on differential light scatter properties followed
      by morphological characterization via light microscopy and software image
      analysis. Cells were identified as hyaline, semigranular, and granular hemocytes
      based on established invertebrate hemocyte classification. A characteristic
      decrease in nuclear size, an increase in granularity between the hyaline and
      granular cells, and the eccentric location of nuclei in granular cells were also
      observed. The granulocyte subpopulations were observed to possess varying degrees
      of granularity. The developed methodology was used to perform total and
      differential hemocyte counts from three lake populations and between wild and
      captive crayfish specimens. Differences in total and differential hemocyte counts
      were not observed among the wild populations. However, specimens held in
      captivity for 14 d exhibited a significant 63% reduction in total hemocyte count,
      whereas the relative hemocyte proportions remained the same. These results
      demonstrate the utility of this method for the investigation of subacute stressor
      effects in selected decapod crustaceans.

PMID- 20043408
TI  - Findings from the 2009 EBRI/MGA Consumer Engagement in Health Care Survey.
AB  - FIFTH ANNUAL SURVEY: This Issue Brief presents findings from the 2009 EBRI/MGA
      Consumer Engagement in Health Care Survey, which provides nationally
      representative data regarding the growth of consumer-driven health plans (CDHPs)
      and high-deductible health plans (HDHPs), and the impact of these plans and
      consumer engagement more generally on the behavior and attitudes of adults with
      private health insurance coverage. Findings from this survey are compared with
      four earlier annual surveys. ENROLLMENT LOW BUT GROWING: In 2009, 4 percent of
      the population was enrolled in a CDHP, up from 3 percent in 2008. Enrollment in
      HDHPs increased from 11 percent in 2008 to 13 percent in 2009. The 4 percent of
      the population with a CDHP represents 5 million adults ages 21-64 with private
      insurance, while the 13 percent with a HDHP represents 16.2 million people. Among
      the 16.2 million individuals with an HDHP, 38 percent (or 6.2 million) reported
      that they were eligible for a health savings account (HSA) but did not have such
      an account. Overall, 11.2 million adults ages 21-64 with private insurance,
      representing 8.9 percent of that market, were either in a CDHP or were in an HDHP
      that was eligible for an HSA, but had not opened the account. MORE COST-CONSCIOUS
      BEHAVIOR: Individuals in CDHPs were more likely than those with traditional
      coverage to exhibit a number of cost-conscious behaviors. They were more likely
      to say that they had checked whether the plan would cover care; asked for a
      generic drug instead of a brand name; talked to their doctor about prescription
      drug options, other treatments, and costs; asked their doctor to recommend a less
      costly prescription drug; developed a budget to manage health care expenses;
      checked prices before getting care; and used an online cost-tracking tool. CDHP
      MORE ENGAGED IN WELLNESS PROGRAMS: CDHP enrollees were more likely than
      traditional plan enrollees to report that they had the opportunity to fill out a
      health risk assessment, whereas they were equally likely to report that they had
      access to a health promotion program. CDHP enrollees were more likely than
      traditional plan enrollees to participate when a program was offered. Among those
      not participating, they did not participate because they could make changes on
      their own; they lacked time; and they were already healthy. FINANCIAL INCENTIVES
      MATTER: Financial incentives for healthy behavior mattered more to CDHP enrollees
      than traditional plan enrollees. Financial incentives were a larger factor for
      CDHP enrollees than for traditional plan enrollees when it came to participating
      in wellness programs, choice of doctor, and the use of health information
      technology, as well as patient engagement using e-mail and the Web. HEALTH STATUS
      IS BETTER, INCOME HIGHER: Adults in CDHPs were significantly less likely to have
      a health problem than were adults in HDHPs or traditional plans. Adults in CDHPs
      and HDHPs were significantly less likely to smoke than were adults in traditional
      plans, and were significantly more likely to exercise. People in CDHPs were also
      less likely to be obese compared with adults enrolled in a traditional health
      plan. Adults in CDHPs were significantly more likely than those with traditional
      health coverage to have a high household income. CDHP and HDHP enrollees were
      also more likely than traditional plan enrollees to be highly educated.

PMID- 20043409
TI  - The most critical 16 minutes in marketing.

PMID- 20043410
TI  - Scanning a new horizon. Hospital CEOs need to learn more about the Web's
      possibilities.

PMID- 20043411
TI  - Healthcare's best-kept secret. The most valuable research tool is the one you
      might not be using.

PMID- 20043412
TI  - The new era of connected care. Marketing and IT find common ground at last.

PMID- 20043413
TI  - Keeping tabs. How personal health records are changing the face of healthcare.

PMID- 20043414
TI  - Lines in the sand. Companies can't afford to ignore the benefits of integrated
      marketing.

PMID- 20043415
TI  - Through thick and thin. Client-agency relationships are changing. Is your company
      prepared?

PMID- 20043416
TI  - Marketers must focus on patient satisfaction.

PMID- 20043417
TI  - Permission to thrive. Interview by Gilgoff Dan.

PMID- 20043418
TI  - Success is... Real-life victory stories.

PMID- 20043419
TI  - From lizard to lab to you.

PMID- 20043420
TI  - Sharing the love.

PMID- 20043421
TI  - Leadership from the start.

PMID- 20043424
TI  - Ibuprofen and warfarin.

PMID- 20043423
TI  - Acute coronary syndrome.

PMID- 20043425
TI  - Right information at the right time.

PMID- 20043426
TI  - Effective teamwork in trauma management.
AB  - The emergency department (ED) education team at the Queen's Medical Centre,
      Nottingham, has developed a process to promote effective teamwork in major trauma
      management. To introduce this process to ED staff, the team developed a
      multiprofessional education and training programme. This article describes the
      development process, explains how and why it was undertaken, and provides details
      of the education and training programme. It also highlights the challenges met by
      the education team during implementation.

PMID- 20043427
TI  - Taking services to the streets over the party season.
AB  - Christmas and New Year festivities notoriously result in increased attendance at
      emergency departments (EDs). The knock-on effect of this in Solihull, in the West
      Midlands, is that, when ambulance staff and police accompany patients to
      hospital, the locality is temporarily under-resourced by these services. To
      address this problem, a collaborative project was implemented to enable advanced
      clinical practitioners, with consultant support, to assess, treat and potentially
      discharge patients from a specially constructed emergency facility situated in
      Solihull town centre. This has reduced the number of ED admissions and transfers,
      and resulted in significant cost and time savings for the ambulance service.

PMID- 20043428
TI  - Nurse interventions in ambulance command-and-control centres.
AB  - As a result of a merger between NHS Direct in Wales and the Welsh Ambulance
      Services NHS Trust, an initiative in which nurses assess the presenting symptoms
      of people who call for emergency services has been launched. This article
      describes how the initiative has ensured that patients receive the services they
      need, reduced the number of inappropriate ambulance call-outs and helped the
      nurses involved to improve their practice.

PMID- 20043429
TI  - Irrigation of the eye after alkaline and acidic burns.
AB  - Chemical eye injury is considered an emergency that needs immediate nursing
      intervention because prognoses depend, not only on severity of injury, but also
      on the promptness and effectiveness of eye irrigation. Many nurse practitioners
      working in emergency care settings have limited knowledge of chemical eye
      injuries and may understand only partially what course of action to take. This
      article explains briefly the effects of chemicals on ocular tissues and how to
      carry out an irrigation procedure before referring patients to ophthalmologists.

PMID- 20043430
TI  - Agenda for change in emergency care settings.
AB  - In 2004, the NHS Knowledge and Skills Framework (Department of Health 2004) was
      launched as part of Agenda for Change, the new terms and conditions for most NHS
      staff. Five years on, it has been introduced across the U.K. with varying degrees
      of success. This article describes the fundamentals of the KSF appraisal system,
      its use as a staff-assessment tool and its application in emergency care
      settings.

PMID- 20043431
TI  - Emergency care for young people who have used cocaine.
AB  - Government figures suggest that there has been an increase in the number of young
      people using cocaine. Emergency and minor injury unit nurses are therefore
      increasingly likely to care for these people. This article describes the
      presenting symptoms and management of a patient who had an adverse reaction to
      cocaine, briefly examines the issues of 'adolescent consent' and discusses
      cocaine use among young people.

PMID- 20043432
TI  - When and why Filipino mothers of term low birth weight infants interrupted
      breastfeeding exclusively.
AB  - This paper makes use of data collected in a randomised controlled trial that was
      designed to test the efficacy of postpartum breastfeeding counselling to increase
      exclusive breastfeeding among term low birth weight infants in Manila during the
      first six months. Mothers were randomised to a control group or one of two home
      visit interventions: by trained breastfeeding counsellors or child care
      counsellors without breastfeeding support training. Sixty mothers received peer
      breastfeeding counselling while a further 119 mothers did not. The median
      duration of exclusive breastfeeding among mothers who received counselling was
      five weeks versus two weeks among those who received no counselling (p<0.001).
      Exclusive breastfeeding was interrupted to offer infants water, traditional
      herbal extracts or artificial baby milk. Mothers who interrupted exclusive
      breastfeeding claimed they had insufficient milk or that their infants had slow
      weight gain. Early and sustained breastfeeding support will enable mothers to
      exclusively breastfeed low birth weight infants for the first six months.

PMID- 20043433
TI  - A study of in-hospital midwifery practices that affect breastfeeding outcomes.
AB  - Whilst breastfeeding is undoubtedly best for both mother and baby, many factors
      influence a woman's decision about whether to start and when to cease feeding.
      This study sought to determine which variables, influenced by midwifery practice,
      may influence the length of breastfeeding. Mothers who had given birth to a live
      baby at a Perth private hospital were invited to complete a validated, anonymous
      questionnaire asking about their breastfeeding experience, both in hospital and
      following discharge. The response rate was 50% (n=266). Although 94% of women
      were breastfeeding on discharge from hospital, this rate reduced to 59% at 6
      months and 21% at 12 months. The mean duration of breastfeeding was 7.4 months
      (SD +/- 4.1). Of five variables thought to be associated with an increased length
      of breastfeeding, only two were found to be statistically significant: whether a
      mother could independently attach the baby on discharge (p=0.003) and whether or
      not artificial baby milk was administered in hospital (p<0.001). In order to
      improve breastfeeding rates, education for both mothers and midwives must be
      targeted towards ensuring mothers are able to independently attach their baby on
      discharge from hospital. The findings also support the discouragement of
      artificial feeding unless there is a medical indication or the mother has made an
      informed request.

PMID- 20043434
TI  - Psychological stress and breast diseases during lactation.
AB  - Termination of breastfeeding in the first six months after childbirth is
      frequently caused by breastfeeding-related diseases and problems of the breast
      such as pain, milk stasis or mastitis. The aim of this study was to evaluate the
      relationship between psychological stress and the occurrence of breastfeeding
      associated disorders. In a prospective cohort study of 379 primiparous women
      without breast anomalies or diseases, psychometric data were collected from
      participants between the confirmation of the pregnancy and one year post-partum.
      Primarily, standardised questionnaires (PSQ, WHO QoL and F-SOZU K22) were used
      for data analysis while additional data was gathered in follow-up interviews. The
      subgroup analysis showed a significant relationship between stress and
      breastfeeding-related diseases. Women with pain, cracked nipples, milk stasis or
      mastitis reported a higher stress level than women without breast problems.
      Additionally, the majority of women with breast problems and increased
      psychological stress gave up breastfeeding sooner and, in contrast to the group
      without problems, indicated significantly more frequently that the milk quantity
      was insufficient. Breast diseases during lactation are associated with higher
      levels of psychological stress. Further studies are needed to examine the causes
      of the higher stress in order to develop strategies to prolong breastfeeding
      duration.

PMID- 20043435
TI  - Valuing nurses' psychological skills.

PMID- 20043438
TI  - The angry manager's course--better bullying through science.

PMID- 20043439
TI  - Language barriers hinder diabetes prevention.

PMID- 20043440
TI  - What competencies do nurse educators need?

PMID- 20043441
TI  - Extolling the benefit of postgraduate education.

PMID- 20043442
TI  - Combatting negative images of nursing.

PMID- 20043443
TI  - Improving quality care in emergency departments.

PMID- 20043444
TI  - Taking the issue of bullying seriously.

PMID- 20043445
TI  - Assessing practice through clinical conversations.

PMID- 20043446
TI  - Marketing nursing to secure the profession's future.

PMID- 20043447
TI  - Education empowers.

PMID- 20043448
TI  - Te Poari meets.

PMID- 20043449
TI  - Valuing leadership.

PMID- 20043450
TI  - Army dentistry in Hawaii.

PMID- 20043451
TI  - History of Navy dental care in Hawaii.

PMID- 20043452
TI  - Navy dentistry.

PMID- 20043453
TI  - Dentistry in the Marine Corps.

PMID- 20043454
TI  - Dentistry on the frontier.

PMID- 20043455
TI  - Military dental readiness & you.

PMID- 20043456
TI  - Dealing with employment issues.

PMID- 20043457
TI  - Professional courtesy please.

PMID- 20043458
TI  - Providers collaborate on quality initiatives. Two new reports show heartening
      progress in quality achievements.

PMID- 20043459
TI  - Cultural competence counts. A Minnesota provider illustrates how awareness and
      education can bridge gaps and improve quality of life for minority populations.

PMID- 20043460
TI  - A shift in the HIT spending curve. A provider develops a road map with
      implementation strategies.

PMID- 20043461
TI  - Histologic subtype in NSCLC: does it matter?
AB  - Platinum-based doublet chemotherapy remains the cornerstone of therapy in the
      first-line setting in advanced non-small-cell lung cancer (NSCLC) for patients
      with good performance status. However, this paradigm has recently been challenged
      by the results of a study that showed a survival benefit with the addition of
      bevacizumab to carboplatin and paclitaxel in bevacizumab-eligible patients and by
      the superior efficacy of gefitinib and erlotinib compared to chemotherapy in
      epidermal growth factor receptor (EGFR) gene mutation-positive tumors (mainly
      adenocarcinomas). In addition, histology has been recently recognized as a
      potential predictive factor in advanced NSCLC patients treated with chemotherapy.
      Prospective data from a preplanned subgroup analysis of a phase III study and
      retrospective reviews consistently reported a significant interaction between
      treatment by histology and response/survival in nonsquamous NSCLCs treated with
      pemetrexed, compared to squamous cell carcinoma (SCC). Thymidylate synthase, the
      main target of pemetrexed, was found to be differentially expressed among the
      histotypes of lung cancer, being lower in adenocarcinoma and higher in SCC and
      small-cell lung cancer. Thus, the availability of adequate amounts of tissue from
      biopsies to allow accurate pathologic subclassifications at diagnosis will be
      critical to help the oncologist select the most appropriate chemotherapy regimen
      as we move toward an individualized molecularly based approach.

PMID- 20043462
TI  - Histology... For want of anything better?

PMID- 20043463
TI  - Subdividing NSCLC: reflections on the past, present, and future of lung cancer
      therapy.

PMID- 20043464
TI  - Peripheral T-cell lymphomas: their time has come.

PMID- 20043465
TI  - Current management of primary cutaneous CD30+ T-cell lymphoproliferative
      disorders.
AB  - Primary cutaneous CD30+ T-cell lymphoproliferative disorders (PCLPDs) are the
      second most common type of cutaneous T-cell lymphoma. These disorders comprise a
      spectrum of clinically benign lymphomatoidpapulosis (LyP) and primary cutaneous
      anaplastic large-cell lymphoma (ALCL). The peak incidence of LyP is in the 5th
      decade of life, and the incidence of primary cutaneous ALCL peaks in the 6th
      decade, but children are also affected. Both LyP and primary cutaneous ALCL have
      an excellent prognosis. However, LyP is associated with development of malignant
      lymphoma (mycosis fungoides, Hodgkin lymphoma, or ALCL) in 20% of cases, and also
      with an increased risk of non-lymphoid cancers. The diagnosis of LyP is difficult
      and often delayed. Primary cutaneous ALCL must be distinguished from secondary
      skin lesions in systemic ALCL, which confer a poor prognosis. Correlation of
      clinical findings with histopathology and immunopathology (stains for ALK kinase,
      epithelial membrane antigen, and cutaneous lymphocyte antigen) are important to
      achieve a correct diagnosis. When a diagnosis of CD30+ PCLPD is established,
      minimal clinical staging is required. Low-dose methotrexate (10-25 mg weekly) is
      the most effective therapy for PCLPD but is usually reserved for aggressive cases
      of LyP and multifocal lesions of cutaneous ALCL Many patients with LyP can be
      followed expectantly, with special attention to changes in character of the skin
      lesions or development of lymphadenopathy. Patients with localized cutaneous ALCL
      can be treated with irradiation. Extracutaneous spread of disease is an
      indication for multiagent chemotherapy. Other treatment alternatives are
      discussed.

PMID- 20043466
TI  - Diagnostic and therapeutic challenges of primary cutaneous lymphomas.

PMID- 20043467
TI  - The importance of accurately characterizing lymphoproliferative disease.

PMID- 20043468
TI  - Eltrombopag for the treatment of chronic immune (idiopathic) thrombocytopenic
      purpura.
AB  - PURPOSE: On November 20, 2008, eltrombopag (Promacta) received approval from the
      US Food and Drug Administration (FDA) for the treatment of thrombocytopenia in
      patients with chronic immune thrombocytopenic purpura (ITP) who have had an
      insufficient response to corticosteroids, immunoglobulins, or splenectomy. This
      report summarizes the FDA analyses of the clinical data supporting this approval.
      EXPERIMENTAL DESIGN: The FDA reviewed data from two double-blind, placebo
      controlled clinical studies, an uncontrolled extension study, and exploratory
      supportive studies. One study randomized patients among placebo or one of three
      daily doses of eltrombopag (30, 50, or 75 mg). The other study randomized
      patients between placebo or eltrombopag, 50 mg daily. Study drugs were
      administered for 6 weeks. The primary endpoint was response rate. Patients who
      completed these and other studies were eligible to enroll in the extension study.
      RESULTS: Overall, 231 patients were randomized within the two controlled studies
      (67 to placebo; 164 to eltrombopag). A platelet response was observed among 59%
      and 70% of the patients receiving eltrombopag, 50 mg daily. Corresponding placebo
      response rates were 16% and 11%, respectively. Serious hemorrhages occurred among
      two patients receiving eltrombopag and one patient receiving placebo, and among
      five patients following discontinuation of eltrombopag. In the extension study,
      eltrombopag was administered to 109 patients; median platelet counts were > 50 x
      10(9)/L throughout the study's quarterly follow-up points. Major safety findings
      pertained to a risk for hepatotoxicity, worsened thrombocytopenia with hemorrhage
      following eltrombopag discontinuation, and bone marrow reticulin formation.
      CONCLUSIONS: The US FDA approved eltrombopag for use among certain patients with
      chronic ITP based upon demonstration of a favorable risk-to-benefit profile,
      where the major benefit pertained to demonstration of a clinically important
      increase in blood platelets among a population of patients relatively refractory
      to prior therapies.

PMID- 20043469
TI  - Update on eltrombopag for ITP.

PMID- 20043470
TI  - Oxygen therapies.
AB  - Oxygen therapies are unproven alternatives promoted as a cure for cancer,
      acquired immune deficiency syndrome (AIDS), and other degenerative diseases.
      These "therapies" are offered at clinics in Mexico, the United States, and
      Europe. Proponents claim that many diseases, including cancer, are caused by
      oxygen deficiency and that oxygenation can restore health by destroying cancer
      cells, eliminating pathogens, stimulating metabolism, and by producing "oxidative
      detoxification." There is no scientific evidence to support any of these claims.
      Oxygen therapies include: (1) hydrogen peroxide therapy involving intravenous
      infusion, ingestion, colonic administration, or soaking in hydrogen peroxide
      solution; (2) ozone colonies and ozone autohemotherapy, in which blood is
      withdrawn and treated with ozone before reinfusion, and (3) "oxygenated" water,
      pills, and solutions. The use of oxygen therapies has resulted in serious adverse
      events and several deaths. Oxygen therapies should not be confused with those
      commonly used in respiratory care.

PMID- 20043471
TI  - Floored. New floor-covering provides hospital with many benefits.

PMID- 20043472
TI  - All better. Striking children's hospital key to campus renewal.

PMID- 20043473
TI  - Lost + found: making the right choice in equipment location systems.

PMID- 20043474
TI  - Value as a virtue. Designing attractive health care spaces on a budget.

PMID- 20043475
TI  - Green ops. Auditing facilities for environmental performance.

PMID- 20043476
TI  - Imaging experience. Technology is only part of the design equation.

PMID- 20043477
TI  - Clean and green. Achieving sustainability in the ES department.

PMID- 20043478
TI  - Drug diversion in the OR: how can you keep it from happening?

PMID- 20043479
TI  - DNV offers a new accreditation choice.

PMID- 20043480
TI  - OR leaders hear about culture of safety.

PMID- 20043481
TI  - Pendulum swings on glucose control.

PMID- 20043482
TI  - Bringing evidence to the OR supply chain.

PMID- 20043483
TI  - CMS clarifies use of flash for ASCs.

PMID- 20043484
TI  - Building a strong ASC QI program.

PMID- 20043485
TI  - IT leaders: prepare for personalized medicine. PM is a disruptive force in
      medical practice that has been evolving rapidly over the last few years.

PMID- 20043486
TI  - Prospective payment and the new perspective.

PMID- 20043487
TI  - Organized security. To address compliance and IT security, Piedmont Healthcare
      chose to establish baseline metrics for it security risk.

PMID- 20043488
TI  - Keep patients on track in the ED. Electronic health-record implementation
      provides dramatic productivity improvements, $600,000 in annual savings, and a
      return on investment of slightly more than two years.

PMID- 20043489
TI  - Telehealth network connects rural Nebraska. Wireless mobile-computing
      workstations are instrumental in bringing three dialysis facilities together for
      videoconferencing.

PMID- 20043490
TI  - The future of patient monitoring.

PMID- 20043491
TI  - Wisconsin HIE optimizes community care. Communication among ED clinicians and
      federally qualified health centers in the Milwaukee area was improved, including
      real-time access to patient historical-encounter data.

PMID- 20043492
TI  - The bottom-up approach to HIEs. Bypassing third-party governance allows Spectrum
      Health to meet physician-practice needs across three hospital systems.

PMID- 20043493
TI  - Healthcare reform--the impact on IT.

PMID- 20043494
TI  - John M. Eisenberg Patient Safety and Quality Awards.
AB  - The Joint Commission Journal on Quality and Patient Safety is honored to publish
      articles on the recipients of the annual John M. Eisenberg Patient Safety and
      Quality Awards. This year, a new category was created: individual achievement at
      the international level.

PMID- 20043495
TI  - An interview with Gary Kaplan. Interviewed by Cathie Furman.

PMID- 20043496
TI  - An interview with Tejal Gandhi. Interviewed by David W. Bates.

PMID- 20043497
TI  - An interview with Noreen Zafar. Interviewed by Steven Berman.

PMID- 20043498
TI  - Preventing central line-associated bloodstream infections and improving safety
      culture: a statewide experience.

PMID- 20043499
TI  - Use of the Modified Early Warning Score decreases code blue events.

PMID- 20043500
TI  - Empowering frontline nurses: a structured intervention enables nurses to improve
      medication administration accuracy.
AB  - BACKGROUND: Seven hospitals from the San Francisco Bay Area participated in an 18
      month-long Integrated Nurse Leadership Program, which was designed to improve the
      reliability of medication administration by developing and deploying nurse
      leadership and process improvement skills on one medical/surgical inpatient unit.
      METHODS: Each hospital formed a nurse-led project team that worked on six safety
      processes to improve the accuracy of medication administration: Compare
      medication to the medication administration record, keep medication labeled from
      preparation to administration, check two forms of patient identification, explain
      drug to patient (if applicable), chart immediately after administration, and
      protect process from distractions and interruptions. RESULTS: For the six
      hospitals included in the analysis, the accuracy of medication administration (as
      measured by the percent of correct doses administered) improved from 85% in the
      baseline period to 92% six months after the intervention and 96% 18 months after
      the intervention. The sum of the six safety processes completed also improved
      significantly, from 4.8 on a 0-6 scale at baseline to 5.6 at 6 months to 5.75 at
      18 months. DISCUSSION: This study suggests that frontline nurses and other
      hospital-based staff, if given the training, resources, and authority, are well
      positioned to improve patient care and safety processes on hospital patient
      units. Frontline clinicians have the unique opportunity to see what is and is not
      working in the direct provision of patient care. To address the sustainability of
      the program's changes after the official project ended, each team was required to
      develop a sustainability plan entailing monitoring of progress, actions to ensure
      the improvements are built into the organizational infrastructure, and staff's
      interaction with leaders to ensure that the work could continue.

PMID- 20043501
TI  - Improving inpatients' identification of their doctors: use of FACE cards.
AB  - BACKGROUND: Improving patients' ability to identify their inpatient physicians
      and understand their roles is vital to safe patient care. Picture cards were
      designed to facilitate physician introductions. The effect of Feedback Care and
      Evaluation (FACE) cards on patients' ability to correctly identify their
      inpatient physicians and on patients understanding of physicians roles was
      assessed. METHODS: In October 2006, team members introduced themselves with FACE
      cards, which included a photo and an explanation of their roles. During an
      inpatient interview, research assistants asked patients to name their inpatient
      physicians and trainees and to rate their understanding of their physicians'
      roles. RESULTS: Of 2,100 eligible patients, 1,686 (80%) patients participated in
      the baseline period, and 857 (67%) of the 1,278 patients in the intervention
      period participated in the evaluation. With the FACE intervention, patients were
      significantly more likely to correctly identify at least one inpatient physician
      (attending, resident, or intern; baseline 12.5% versus intervention 21.1%; p <
      .001). Of the 181 patients who were able to correctly identify at least one
      inpatient physician in the intervention period, research assistants noted that
      59% (107) had FACE cards visible in their rooms. Surprisingly, fewer patients
      rated their understanding of their physicians' roles as excellent or very good in
      the intervention period (45.6%) compared with the baseline period (55.3%; p <
      .001). DISCUSSION: Although FACE cards improved patients ability to identify
      their inpatient physicians, many patients still could not identify their
      inpatient doctors. FACE cards may have served as a reminder to physicians to
      introduce themselves to their patients. The FACE cards also served to highlight
      patients' misunderstanding of their physicians' roles.

PMID- 20043502
TI  - Postdischarge adverse events in children: a cause for concern.

PMID- 20043503
TI  - A strategy for real-time identification of hospitalized patients with heart
      failure.

PMID- 20043504
TI  - NICE updates guidance on tackling depression.

PMID- 20043505
TI  - Obstructive sleep apnoea increases risk of CVD.
AB  - In OSA, the patient suffers repeated episodes of apnoea caused by narrowing or
      closure of the pharyngeal airway during sleep. The degree of closure of the
      airway leads to periods of either apnoea (complete) or hypopnoea (partial)
      obstruction. Population-based surveys estimate that 2-4% of the middle-aged
      population have OSA, which is similar to the prevalence of diabetes and asthma.
      Although understanding of the condition has improved considerably, it is
      estimated that 85-90% of sufferers still remain undiagnosed. OSA is not only a
      cause of excessive daytime somnolence leading to an increased risk of accidents
      on the road and poor work performance, but also a major cause of social
      dysfunction, reduced quality of life related to poor health, and mood disorders.
      Untreated OSA predicts a substantially increased risk of hypertension,
      cardiovascular disease, cerebrovascular disease, depression, and mortality.
      Wherever OSA is considered, the following questions should be asked: Is this
      patient falling asleep regularly against their will? Is this patient often sleepy
      while driving? Is this patient experiencing difficulty at work because of
      excessive sleepiness? Is sleep refreshing? Is surgery for snoring being
      considered (OSA should be excluded first)? The gold standard for investigation of
      OSA is polysomnography. It is possible to diagnose almost 90% of OSA patients
      from limited sleep studies often conducted on a domiciliary basis with portable
      diagnostic equipment.

PMID- 20043506
TI  - Managing LRTI in adults in the community.
AB  - When considering a diagnosis of LRTI the main differentiation to make is between
      pneumonia and non-pneumonic LRTI. It is more difficult to make this distinction
      in the community because of access constraints to chest radiography and the lack
      of a quick, simple marker to identify patients with true pneumonia accurately.
      The diagnosis of pneumonia in the community, without a chest radiograph, is
      suggested by symptoms that include: cough; (purulent) sputum production;
      breathlessness; pleurisy; occasional haemoptysis along with new focal signs on
      chest examination (e.g. crepitations, bronchial breathing, and dullness to
      percussion); at least one systemic feature (e.g. sweating, fevers, shivers, aches
      and pains and/or temperature >38 degrees C); and no other explanation for the
      symptoms. A recent observational study of around 150,000 patients with LRTI in
      the UK found that the following factors were associated with increased
      respiratory infection-related mortality: increasing age; smoking; increasing
      Charlson co-morbidity index; prior antibiotic prescribing; frequent consultation
      and prior specialist referral or admission. Acute adult LRTI presenting to GPs is
      a predominantly viral illness most commonly caused by rhinoviruses and influenza
      viruses. The most common bacterial cause of pneumonia is Streptococcus pneumoniae
      but frequently no organism is identified. In patients where you suspect non
      pneumonic LRTI, the evidence suggests that chest radiography and blood tests for
      CRP are not helpful in their management in the community. The BTS guidelines
      recommend that GPs, particularly those working in out-of-hours and emergency
      assessment centres, should consider using pulse oximeters. The CRB-65 is a
      helpful tool in the community. Patients scoring 0 or 1 have the lowest mortality
      risk, however, a score of 2 or more should be a cause for concern and the patient
      may need to be admitted to hospital for assessment.

PMID- 20043507
TI  - HIV testing in primary care will help improve early diagnosis.
AB  - HIV is now a treatable medical condition and the majority of those diagnosed with
      the virus remain fit and well on treatment. Patients living with HIV may well now
      have a near-normal life expectancy with antiretroviral treatment. In all, 77,000
      people are known to be infected with HIV in the UK. However, 28% are unaware of
      their infection and are therefore unable to access treatment. Late diagnosis is
      the most important factor associated with HIV-related morbidity and mortality in
      the UK. The RCP guidelines recommend that GPs should offer an HIV test to
      patients: from communities or geographical locations where HIV is common; who
      present with a medical condition in which HIV might be implicated; with a medical
      condition compatible with AIDS or with any HIV indicator disease. GPs should also
      consider offering an HIV test to new patients who register with the practice in
      areas where diagnosed HIV prevalence in the local population (PCT/LA) exceeds 2
      in 1,000. The pre-test discussion should cover: an explanation of why the test is
      recommended; the benefits of testing to the individual; details of how the result
      will be given; confidentiality and informed consent. The need for a repeat HIV
      test, if the patient is still within the window after a specific exposure, should
      be discussed.

PMID- 20043508
TI  - Adulteration of food. 1909.

PMID- 20043509
TI  - Fungal infections.

PMID- 20043511
TI  - PEComas: a review with emphasis on cutaneous lesions.
AB  - The connection between angiomyolipoma (AML) of the kidney, clear cell sugar tumor
      (CCST) of the lung, and pulmonary lymphangioleiomyoma (LAM), was progressively
      discovered because of the histologic and immunophenotypic similarities between
      the three tumors and their frequent association with tuberous sclerosis complex
      (TSC). Morphologically, analogous lesions found in other locations are composed
      of the unifying cell, the perivascular epithelioid cell (PEC). PEC tumors (or
      PEComas), other than AML, CCST, and LAM, are not associated with TSC and
      typically occur in middle-aged adult females. These neoplasms are composed of
      nests and fascicles of clear to granular epithelioid and/or spindled cells with a
      consistent arrangement around blood vessels. Characteristically, the cells
      express both melanocytic (usually HMB45) and myogenic (typically actin) markers.
      Although the most common sites are the gastrointestinal and genitourinary tracts,
      approximately 23 cases, to date, of PEComas arising in the skin have been
      reported. Primary cutaneous PEComas also have a predilection for adult females
      and most often present as a painless mass on the extremities. In contrast to
      other sites, the myogenic marker most commonly expressed in PEComas of the skin
      is desmin. Most reported cutaneous PEComas follow a benign course, however, a
      malignant case has been reported. Surgical excision is currently the mainstay of
      treatment.

PMID- 20043512
TI  - Cutaneous CD30 lymphoproliferative disorders and similar conditions: a clinical
      and pathologic prospective on a complex issue.
AB  - We elaborate on the diagnosis of CD30 positive cutaneous lymphoproliferative
      conditions including the various clinical and pathological presentations, our
      understanding of its pathomechanisms and prognostic implications. The most common
      reactive conditions that can simulate CD30 lymphoproliferative conditions,
      including arthropod bite reactions, various viral infections, pityriasis
      lichenoides and lymphocytic papules in myelodysplastic syndrome, are discussed in
      detail.

PMID- 20043513
TI  - Postradiation cutaneous vascular tumors of the breast: a review.
AB  - Postradiation vascular tumors fall into two categories: (1) postradiation
      cutaneous angiosarcoma, malignant vascular neoplasms with significant morbidity
      and mortality; and (2) atypical vascular lesions (AVL), vascular tumors that
      reportedly behave in a benign manner. Postradiation vascular tumors not only
      present a therapeutic problem for clinicians, but they present an increasingly
      common diagnostic dilemma for pathologists. Although first described separately
      15 years ago, the relationship between postradiation cutaneous angiosarcoma and
      AVL remains controversial. It appears that, in at least some cases, angiosarcoma
      can arise in the context of AVL, suggesting that these lesions are part of a
      spectrum of the same disease process. This latter view point is supported by the
      significant clinical and histologic overlap found between both tumors. Herein, we
      will discuss the evolution of this topic while reviewing the various clinical,
      histopathologic, and prognostic characteristics of postradiation cutaneous
      angiosarcoma and AVL.

PMID- 20043515
TI  - Fueling cultural change.

PMID- 20043514
TI  - Keratoacanthoma: hyperplasia, benign neoplasm, or a type of squamous cell
      carcinoma?
AB  - Keratoacanthomas are common self limited squamous proliferations. They have been
      considered a benign neoplasm with involution and complete resolution within few
      months. Although considered the prototypical example of cutaneous
      pseudomalignancy, some believe that these tumors are squamous cell carcinomas and
      through the years there have been sporadic reports of "metastasizing
      keratoacanthomas". The question has been raised as to whether keratoacanthoma is
      an unreliable histological diagnosis or these tumors have a latent, albeit rare,
      malignant potential. To date, just a handful of "metastasizing keratoacanthomas"
      have been reported. Since a benign lesion is incapable of metastasis, some other
      explanation must be considered; the most likely one being a misdiagnosis. While
      it is clear that in some cases, the histological and cytological features of
      squamous cell carcinoma and keratoacanthoma are difficult to distinguish by
      current techniques, these occasional limitations in diagnosis do not make
      keratoacanthomas a carcinoma. We believe the evidence supports that
      keratoacanthomas are benign squamous proliferations. The diagnosis can be made
      with confidence in appropriate biopsies and using well established
      clinicopathological criteria.

PMID- 20043516
TI  - Combustible dust raises explosive issues.

PMID- 20043517
TI  - The next AED?

PMID- 20043518
TI  - Move big loads safely.

PMID- 20043519
TI  - The future of safety: 2010 and beyond.

PMID- 20043520
TI  - Contemporary issues in process hazard analysis.

PMID- 20043522
TI  - Flexibly equipped.

PMID- 20043521
TI  - Faster detection adds safety.

PMID- 20043523
TI  - Bronchial asthma--patient expectations and the role in asthma care.

PMID- 20043524
TI  - High genetic diversity in human immunodeficiency virus-type 1 in Jamaica.
AB  - The subtypes of the human immunodeficiency virus - type 1 (HIV-1) strains from 54
      HIV-1 - infected persons including 44 strains which were typed previously by
      heteroduplex mobility assay (HMA) were determined by DNA sequencing and
      phylogenetic analysis. Of 54 HIV- infected persons, 92.5% were infected with HIV
      1 subtype B and 7.5% with other HIV-1 subtypes including subtypes D (3.7%), A
      (1.9%) and J (1.9%). In the phylogenetic analysis, the subtype A virus found in
      the sample clustered with subtype A reference strains and a circulating
      recombinant form (CRF) reference strain which originates in Central Africa and is
      circulating in Cuba indicating a close relationship between these viruses. There
      was 86% concordance between HMA and DNA sequencing in assigning subtype B
      viruses. For the non-B subtype viruses, there was less concordance between the
      two methods (67%). The results confirm the predominance of HIV-1 subtype B
      strains and the high genetic diversity of HIV-1 strains in circulation in
      Jamaica. The efficacies and some limitations of the HMA as a method of HIV-1
      subtyping also were noted. It is important that the HIV/AIDS epidemic in Jamaica
      be monitored meticulously for possible expansions in non-B subtypes and the
      emergence of inter-subtype recombinant forms. We recommend that the more
      expensive DNA sequencing and phylogenetic analysis, including HIV-1 genotyping
      for antiretroviral drug resistance testing, be used as an adjunct to the more
      cost-effective HMA to track the HIV/AIDS epidemic in Jamaica.

PMID- 20043525
TI  - A randomized comparison of rectal misoprostol with syntometrine on blood loss in
      the third stage of labour.
AB  - OBJECTIVES: a) To compare the clinical effect of rectal misoprostol with
      intramuscular syntometrine in reducing blood loss in the third stage of labour b)
      to determine the severity and incidence of side effects of both drugs and c) to
      measure blood loss, patient tolerance and acceptance of rectal misoprostol.
      METHODS: One hundred and forty parturients were randomly allocated to receive
      intramuscular syntometrine (syntocinon 10 IU + ergometrine 0.5 mg) or rectal
      misoprostol 400 microg within five minutes of the delivery of the anterior
      shoulder Blood loss was measured by the use of a plastic collection drape.
      Additional oxytocic therapy was instituted for uterine atony or if blood loss was
      in excess of one litre. RESULTS: There was no significant difference in patient
      demographics of each treatment group (Table 1). There was no difference in mean
      duration of the third stage of labour (8.4 +/- 14 min vs 7.8 +/- 6.6 min). The
      mean blood loss from those parturients receiving misoprostol (180.1 +/- 120 mls)
      was not significantly different (p = 0.5) from those receiving syntometrine (197
      +/- 176.97 mls) for the active management of the third stage of labour Treatment
      with syntometrine was associated with a significant elevation of post-partum
      systolic blood pressure compared with misoprostol treatment (mean increase 0.57
      +/- 18.79 mmHg vs -1.43 +/- 14.17 mmHg, (mean +/- SD), p < 0.04). Rectal
      misoprostol was well tolerated in 88.5% of participants, 11.4% reported that
      insertion was uncomfortable, of which 2.8% reported that they would have
      preferred parenteral drug administration. CONCLUSION: The clinical effect of
      rectal misoprostol and intramuscular syntometrine were not different at the doses
      used in the active management of the third stage of labour in this study. Rectal
      misoprostol was well tolerated by the patients and had a low side effect profile.
      Blood loss assessment using the blood collection drape is of invaluable benefit
      in resource-poor settings.

PMID- 20043526
TI  - Imipramine induced elevation of prolactin levels in patients with HIV/AIDS
      improved their immune status.
AB  - Prolactin is known to have significant immunomodulatory properties. Imipramine, a
      monoamine oxidase inhibitor stimulates prolactin production because it decreases
      dopamine which inhibits secretion of prolactin. The study objective was to
      determine if use of imipramine can result in immunological benefits for HIV
      positive patients by restoration and preservation of immunological function. A
      cohort of 19 retroviral positive patients was identified for the prospective
      study which continued for a 28-week period. Three patients dropped out before the
      study began. Inclusion criteria accepted only patients on the same highly active
      antiretroviral therapy (HAART) regimen for a nine-month period and who had
      reached a plateau with respect to the CD4 cell count and also had no prior
      history of antidepressant use for a 12-month period. This study had a "before and
      after" design, patients serving as their own control. The study drug imipramine
      was prescribed for a 12-week period up to visit 4, and then discontinued for 4
      weeks (washout period) at which time blood investigations were done at visit 5.
      Finally, patients were prescribed the study drug for a further 12-week period to
      the end of the trial (visit 7). At the 95 per cent probability level, significant
      differences in average prolactin and CD4 levels from visit 4 to the end of the
      trial period were recorded. Results showed a trend of prolactin levels decreasing
      after washout (p = 0.015) and increasing by the end of the trial period once
      imipramine dispensation had recommenced (p = 0.006). With respect to the CD4 cell
      count, there was a significant increase after wash-out (p = 0.022). These results
      indicate a trend to immune boosting in HIV-positive patients who had obtained the
      maximum response from HAART.

PMID- 20043527
TI  - Evaluation of asthma control using patient based measures and peak expiratory
      flow rate.
AB  - OBJECTIVE: Asthma control has not been formally evaluated in the Caribbean. This
      study evaluated disease control on The Asthma Control Test (ACT), The Royal
      College of Physicians "Three questions" for Assessing Asthma Control (RCP), peak
      expiratory flow rate (PEFR) and patients' self-assessment of control. SUBJECTS
      AND METHODS: Asthma control was examined in a cross-section of 205 asthmatics
      above 16 years of age using the ACT, RCP and on the PEFR % predicted. Scores
      below 20 and equal to or above 1 on the ACT and RCP respectively, and PEFR below
      80% predicted indicated uncontrolled asthma. Patients stated whether they
      perceived their asthma was controlled or uncontrolled. RESULTS: Overall there
      were more females (63.9%, p < 0.001) than males (36.1%). Males aged between 17-30
      years predominated (60.8%, p < 0.001) with gender reversal beyond 30 years of age
      (33.2%, p < 0.002) years. Self-assessed control was higher (69.3%, p < 0.001)
      than control evaluated by the ACT and RCP tests, which were comparable (p >
      0.05). Fewer patients (13.2%) achieved control on PEFR > 80% predicted than on
      the ACT (22.4%) and RCP (18%). The Kappa statistic indicated good reproducibility
      of the RCP and ACT and concordance between the PEFR and RCP (0.63) and the PEFR
      and ACT (0.56). Higher education was associated with control on the ACT (p <
      0.0005) and RCP (p < 0.002) but not on PEFR or self-assessment (p > 0.05).
      CONCLUSION: Approximately 80% of study asthmatics were uncontrolled, and patients
      tended to overestimate their disease control. The ACT and RCP instruments were
      comparable with the PEFR. Efforts to study their validity and formal evaluation
      of asthma control in Trinidad are recommended.

PMID- 20043528
TI  - Cardiovascular risk profile in Caribbean youth with diabetes mellitus.
AB  - OBJECTIVE: To assess the effect of diabetes mellitus type on conventional and
      novel cardiovascular risk factors in patients, diagnosed with diabetes from two
      major referral hospitals in Jamaica, before age 25 years and with diabetes
      duration < 6 years. METHODS: Participants were classified based on the presence
      of GAD-65 and IA-2 autoantibodies, C-peptide, leptin and clinical phenotype.
      Trained observers obtained anthropometric measurements and sitting blood
      pressure. Fasting blood was taken for glucose, A1c, lipids, high sensitivity C
      reactive protein and lipoprotein profile. RESULTS: Fifty-eight participants (21M;
      37F age 20 +/- 8 [Mean +/- SD] years, diabetes duration 2.6 +/- 2 years) were
      enrolled. Thirty-six had Type 1 diabetes (T1D), thirteen Type 2 diabetes (T2D),
      six were not typed and three had lipoatrophic diabetes. Patients with Type 2
      diabetes (T2D) were more obese with a higher systolic blood pressure but a lower
      A1c than those with Type 1 diabetes (T1D). Total cholesterol, LDL-cholesterol,
      triglycerides, VLDL, LDL and HDL particle numbers were similar in patients with
      T1D and T2D. HDL-cholesterol and LDL and HDL particle sizes were lower in
      patients with T2D but differences were no longer significant after adjusting for
      BMI. CONCLUSIONS: Risk factors for cardiovascular disease are common in patients
      with all forms of youth onset diabetes. Clinicians should therefore investigate
      these risk factors in their patients regardless of diabetes type.

PMID- 20043529
TI  - Cutaneous drug reactions in patients admitted to the dermatology unit at the
      University Hospital of the West Indies, Kingston, Jamaica.
AB  - OBJECTIVE: Cutaneous reactions are among the most common adverse reactions to
      drugs. The purpose of this study is to examine the aetiology and outcome of
      cutaneous drug reactions among patients admitted to the Dermatology Ward at the
      University Hospital of the West Indies. SUBJECTS AND METHODS: This was a
      retrospective study looking at all patients who were admitted with a diagnosis of
      a cutaneous drug eruption from January 1, 1997 to December 31, 2005. Data
      included patient demographics, date of admission to hospital, duration of
      hospitalization and a detailed drug history including any previous episodes of
      drug sensitivity. All drugs reportedly ingested by the patients up to three
      months prior to their cutaneous reaction were documented and the period of time
      between drug ingestion and the appearance of skin lesions was also noted.
      Clinical diagnosis, co-morbidities, histopathological diagnosis, final outcome
      and all ensuing disabilities were noted. The data retrieved were collated and
      analyzed using SPSS 12.0. RESULTS: The results showed a female to male ratio of
      2.2:1. The categories of drugs most commonly implicated were antimicrobials
      followed by anti-epileptic drugs and nonsteroidal anti-inflammatory drugs. The
      most common form of drug eruption requiring admission was the exanthematous drug
      eruption followed by erythema multiforme, toxic epidermal necrolysis and Stevens
      Johnson syndrome. CONCLUSION: In general, the causative agents identified and the
      types of drug eruptions were similar to those found in previous studies. However
      the anti-epileptic drugs, phenytoin and carbamazepine, ranked among the most
      commonly implicated drugs which differ significantly from other studies.

PMID- 20043530
TI  - Chronic renal failure in Jamaican children--an update (2001-2006).
AB  - OBJECTIVE: This study evaluated the incidence, epidemiology, aetiology and
      outcome of chronic renal failure (CRF) in Jamaican children < 12 years old
      between 2001 and 2006. METHODS: The required data on all children who fulfilled
      inclusion criteria were obtained from their medical records at the University
      Hospital of the West Indies, Bustamante Hospital for Children and from
      practitioners in hospitals serving children islandwide. RESULTS: Eighteen new
      children (72.2% male) presented with CRF. The cumulative annual incidence was
      4.61/million child population under age 12 years or 1.14/million total
      population. Congenital urological disease (44.5%) was the commonest cause of CRF,
      followed by glomerulonephritis (33.3%). Half of the cases of glomerulonephritis
      were secondary to HIV-associated nephropathy. Although all children with
      posterior urethral valves were diagnosed before age 6 months and promptly
      treated, renal failure present at birth proved irreversible. The mean age at
      diagnosis of CRF was 6.72 years. Ten children (55.6%) were already in CRF at
      first presentation with renal disease. Of these, the five with non-urological
      disease were already in End Stage Renal Disease (ESRD). Mortality was 44.4%. Five
      children died in ESRD without the benefit of dialysis. CONCLUSION: The incidence
      of CRF has increased from the 1985-2000 local study and is mainly due to
      urological pathology which progresses despite early diagnosis and treatment. Non
      urological renal disease is presenting too late for therapeutic intervention.
      Greater public awareness of symptoms of renal disease is needed. Children's
      access to dialysis is unpredictable. A paediatric dialysis and transplantation
      programme is needed.

PMID- 20043531
TI  - Quality of life in end stage renal disease: a multicentre comparative study.
AB  - BACKGROUND: Quality of Life (QOL) in patients with End Stage Renal Disease (ESRD)
      is an important measure of dialysis adequacy. Health related QOL is an
      independent risk factor for mortality in ESRD. The Kidney Disease QOL
      questionnaire is a highly validated disease targeted instrument with global
      application. We sought to document QOL and the predictive factors in a cohort of
      patients with ESRD in Jamaica and Panama. METHODS: Two hundred patients were
      recruited consecutively from November 2006 - November 2007. Seventy patients were
      from a tertiary hospital based outpatient dialysis centre, the University
      Hospital of the West Indies (UHWI), and 40 patients from a private centre,
      Diabetes Association Renal Unit (DARU) both in Kingston, Jamaica. Ninety patients
      were consecutively recruited from a tertiary hospital based outpatient dialysis
      centre in Panama City, Panama. The Kidney Disease Quality of Life - Short Form
      Questionnaire was administered. Each QOL domain was scored from 0 - 100 with
      higher scores representing better rating. RESULTS: Mean age was 50 +/- 4 years,
      with no difference between the cohorts. Panama, however, had significantly higher
      parameters than the Jamaican cohorts: mean haemoglobin (Hb) 12.4g/dL (p = 0.004),
      mean serum albumin 45g/dL (p = 0.03) and Urea Reduction Ratio (URR) 78% (p =
      0.004). Diabetes Association Renal Unit recorded mean Hb 11.4 +/- 1.3g/dL, mean
      serum albumin 42.1 +/- 2.3g/dL and URR 72%. The University Hospital of the West
      Indies documented mean Hb 11.2 +/- 2.4g/dL, mean serum albumin 41 +/- 4.5g/dL and
      URR 68%. All three cohorts had good overall QOL scores when compared with the
      reference population. Patients from Panama had higher overall QOL scores than
      Jamaican patients (p = 0.02). By centre, UHWI had higher overall QOL scores than
      DARU (p = 0.04). Burden of Kidney Disease domain recorded the lowest overall
      scores (Reference Population 49, DARU 19.0 (p = 0.001), UHWI 24.0 (p = 0.002),
      Panama 32.9 (p = 0.03). Patient Satisfaction scores were also significantly
      reduced across all cohorts (Reference population 72, DARU 52, UHWI 54, Panama
      58). The University Hospital of the West Indies had significantly decreased
      dialysis staff encouragement (p = 0.003). The Diabetes Association Renal Unit
      noted significant reductions in general health (p = 0.04), physical functioning
      (p = 0.001), physical role (p = 0.001) and emotional role (p = 0.005) domains.
      Panama had the lowest overall physical functioning (p = 0.01), pain (p = 0.01)
      and social support (p = 0.04) scores. In the Panamanian cohort, age< 65 years (p
      = 0.0004). Hb > 11.1 g/dL (p = 0.01), albumin > 40g/dL (p = 0.01), URR > 65% (p =
      0.03), race (p = 0.04), at least high school educational attainment (p = 0.01)
      and household yearly salaries > US$5000 (p = 0.002) predicted good QOL scores.
      These accounted for 55% of the variance. In the Jamaican cohort, however, younger
      age (p = 0.02), race (p = 0.001), higher URR (p = 0.01) and higher serum
      haemoglobin (p = 0.001) predicted higher QOL scores, accounting for only 40% of
      the variance. By modality, haemodialysis patients had significantly higher
      haemoglobin (p = 0.003) and albumin (p = 0.002) levels and ultimately higher
      overall QOL scores (p = 0.01). CONCLUSION: Overall, QOL is good in patients with
      ESRD. Domains of highest concern include Burden of Kidney Disease and Patient
      Satisfaction. The role of spirituality, depression and nutritional markers (eg
      prealbumin) needs to be assessed. Quality of Life must therefore be routinely
      documented in ESRD patients and targeted interventions implemented.

PMID- 20043532
TI  - Venous thromboembolism in Jamaican women: experience in a university hospital in
      Kingston.
AB  - OBJECTIVE: To review cases of venous thromboembolism (VTE) at UHWI from 1999
      2004, to identify methods of diagnosis, risk factors and to evaluate differences
      between survivors and fatalities. METHODS: Patients coded with the diagnosis of
      thromboembolism at the University Hospital of the West Indies (UHWI) from 1999
      2004 were identified. The medical records were reviewed to determine the
      prevalence of thromboembolism and possible variables associated with this
      diagnosis. In addition, variables associated with fatality were examined by
      evaluating cases diagnosed at autopsy RESULTS: There were 959 patients coded for
      thromboembolism between 1999-2004 at UHWI. Of these, 657 (68.5%) were females and
      302 were males (31.5%). During that period, 65,657 women and 40,826 men were
      admitted to hospital with prevalence rates for thromboembolism of 1% in women and
      0.7% in men. Of the 657 females, 520 case notes were located (case identification
      80%). Of this, 435 were analysed as confirmed thromboembolism. The median age was
      51 years with a range of 2-95 years. Common associations were obesity, 53.5%; age
      over 50 years, 52.5%; hypertension, 44.7%; immobilisation, 36.3%; cardiac
      disease, 26%; diabetes, 19.4%; fibroids, 16.3%; surgery, 15.8% and cancer 14%.
      Recurrent venous thromboembolism occurred in 12.8% and 15.8 % of women (66) died,
      diagnosed with PE at post-mortem. Using logistic regression analysis, leading
      risk factors in fatalities compared to survivors were hypertension and increased
      age. Obesity and surgery were significantly more likely in survivors. CONCLUSION:
      Venous thromboembolism was common in this cohort of women and avoidance of risk
      factors and institution of prophylaxis in high risk women is important to
      decrease morbidity and mortality.

PMID- 20043533
TI  - Quality of life in Caribbean youth with diabetes.
AB  - BACKGROUND: As the prevalence of youth onset diabetes in Jamaica increases, the
      impact of this disease on Health Related Quality of life (QOL) needs to be
      evaluated. METHODS: Patients from two major referral hospitals had QOL assessed
      using a modified diabetes-39 questionnaire administered by a trained interviewer.
      Subscale scores were transformed to standard scale scores ranging from 0 (lowest
      impact) to 100 (highest impact) and the impact of socio-demographic factors,
      treatment and medical history on QOL examined. RESULTS: Fifty-seven participants
      (21M, 36F, mean age 19.0 +/- 5.1 years, diabetes duration 2.7 +/- 2.2 years, 96%
      black) had QOL assessed. Anxiety and worry had the greatest impact (median score
      = 41) and sexual functioning, the lowest impact (median Score = 0) on QOL. Older
      age, later age of onset, longer diabetes duration, better glucose control and not
      using insulin were associated with a higher anxiety and worry score. Multiple
      regression analysis was conducted to determine which of these were associated
      with the anxiety and worry score after controlling for age. Anxiety and worry
      increased with age (regression coefficient (SE); 2.05[0.68]) and was higher in
      those on oral agents compared to those using insulin (-27.9 [10.9]). CONCLUSION:
      Measures to address anxiety and worry in Jamaican youth with diabetes need to be
      implemented to minimize the impact the disease may have on their QOL.

PMID- 20043534
TI  - Descriptive epidemiology of cases of acute myocardial infarction in Tobago.
AB  - OBJECTIVES: The goal of this study is to identify co-morbidities associated with
      acute myocardial infarction in Tobago. METHODS: This was a longitudinal
      retrospective study of myocardial infarction at the Tobago Regional Hospital in
      two selected periods: January 2007 to April 2007 and January 2008 to April 2008.
      Data were retrieved from the patients' medical records. These included co-morbid
      conditions eg hypertension, diabetes mellitus, dyslipidaemia, ESRD, whether
      history of smoking or cocaine use and if any prior care. In the former period, 11
      cases were confirmed as having myocardial infarction and 27 cases in the latter
      period. RESULTS: In 2007 and 2008, all cases had dyslipidaemia (LDL > 100 mg/dL)
      and were hypertensive. There were 36.4% of cases in 2007 that had diabetes
      mellitus, compared to 33.3% cases in 2008 and 9.1% had chronic kidney disease in
      2007, compared to 25.9% in 2008. CONCLUSION: The most common co-morbidities
      associated with acute myocardial infarction in Tobago are dyslipidaemia,
      hypertension and diabetes mellitus, with ESRD, smoking and cocaine use less so.
      Many of these patients had never received prior care.

PMID- 20043535
TI  - Stroke subtypes on imaging in a Jamaican population: a hospital-based study.
AB  - OBJECTIVE: To examine the pattern of stroke subtypes found on Computed Tomography
      (CT), Magnetic Resonance Imaging (MRI) at the University Hospital of the West
      Indies (UHWI), Kingston, Jamaica. METHOD: A retrospective review was conducted
      for all patients diagnosed with stroke and who were subjected to CT or MRI
      evaluation at UHWI between January 2001 and December 2004. Data were collected
      for patient age and gender and type of stroke. RESULTS: Four hundred and thirty
      three patients were identified and classified as having cerebral infarct, intra
      parenchymal haemorrhage or subarachnoid haemorrhage. There were 414 patients who
      had CT scans and 19 had MRI scans. Within and across genders, over 80% suffered
      infarcts with no significant statistical difference between male and female
      patients. Subarachnoid haemorrhage was the least frequent subtype and occurred in
      younger patients. CONCLUSION: The pattern of stroke subtypes seen in this
      population was similar to that of Australian and European cohorts of patients but
      differed from that reported in Asians. Ischaemic infarct was the most frequent
      stroke subtype followed by intra- parenchymal haemorrhage and subarachnoid
      haemorrhage. There was no gender predilection for any specific type of stroke.

PMID- 20043536
TI  - Renal histological findings in adults in Jamaica.
AB  - BACKGROUND: In 2006, it was reported that Focal and Segmental Glomerulosclerosis
      (FSGS), Minimal Change Disease (MCD) and Membranous Glomerulonephritis (MGN) were
      the commonest primary glomerular diseases identified from percutaneous kidney
      biopsies done in Jamaica for that year (n = 76). The sample size was thought to
      be small and might have affected the reported findings. So a three-year review of
      percutaneous kidney biopsies in Jamaica was carried out. METHODS: Histology
      reports and clinical data were reviewed for percutaneous kidney biopsies
      performed from January 2005 to December 2007. Demographic data (age, gender),
      laboratory investigations such as serum urea, serum creatinine, proteinuria,
      haematuria, 24-hour urinary protein, and creatinine clearance, and clinical
      diagnosis were collected from the histology requisition form. RESULTS: There was
      a total of 224 native kidney biopsies performed. There were 91 males (40.6%) and
      133females (59.4%). Age distribution showed a total number of 25 paediatric cases
      (11.2%) and 199 adult cases (88.8%). Proteinuria was present in 171 cases (76.3%)
      and haematuria in 86 cases (38.4%). Of the total biopsies done, 78 cases (39.2%)
      had primary glomerular diseases, 110 cases (55.3%) had secondary glomerular
      diseases and 11 (5.5%) biopsies were reported as either normal or inadequate for
      histological diagnosis. The most common reasons indicated for percutaneous kidney
      biopsy were proteinuria, haematuria and staging of lupus nephritis. Most common
      histological findings for primary glomerular disease after percutaneous kidney
      biopsy were FSGS (n = 34), MGN (n = 15) and MCD (n = 12). In secondary glomerular
      diseases (n = 110), there were more females (70.8%) than males. Systemic lupus
      erythematosus was present in 63.3%. Histology of lupus nephritis according to the
      International Society of Nephrologists classification shows Membranous Lupus
      Nephritis [MLN] (40.20%), Diffuse Lupus Nephritis [DLN] (19.5%) and Minimal
      Mesangial Lupus Nephritis [MMLN] (14.3%) as the common histological types.
      CONCLUSIONS: The most common histological finding for primary glomerular disease
      following percutaneous kidney biopsy was FSGS, MCD and MGN. Membranous Lupus
      Nephritis was the commonest histological type for lupus nephritis in this series.

PMID- 20043537
TI  - Importance of a renal biopsy.

PMID- 20043538
TI  - Hepatocellular cancer.

PMID- 20043539
TI  - Microbicides: a possible prevention approach to HIV transmission among African
      women.
AB  - Poverty, cultural belief and refusal to use condoms are some of the factors that
      contribute to the spread of HIV infection among African communities. There is a
      dire need to pursue research into the development, provision and the use of
      microbicides for African women. This review paper provides information and
      recommendations on the possible use of microbicides to prevent HIV infection
      among African women.

PMID- 20043540
TI  - An unusual case of bilateral visual loss from metastatic lung cancer.

PMID- 20043541
TI  - Isolated sphenoid aspergilloma: a differential diagnosis for solitary abducens
      nerve palsy.

PMID- 20043542
TI  - Validity, reliability and reproducibility of three methods used to measure tooth
      widths for bolton analyses.
AB  - BACKGROUND: Vernier calipers have traditionally been used as the 'gold-standard'
      for tooth width measurements. New digital methods may prove to be as valid,
      reliable and reproducible as caliper measurements. AIMS: To determine the
      validity, reliability and reproducibility of mesiodistal crown measurements made
      with calipers, using the DigiModel method and on digital photographs, and to
      determine the validity, reliability and reproducibility when the measurements are
      employed in Bolton tooth size analyses. METHODS: Twenty-five consecutive study
      models were used. The maximum mesiodistal crown widths of 12 teeth in each arch
      (first molar to first molar) were measured with digital calipers, using the
      DigiModel software (OrthoProof, Caulfield South, Victoria, Australia) and on
      standardised digital photographs of the models by eight examiners. One examiner
      measured all models three times using the three measurement methods, two
      examiners measured all models once using the three measurement methods and five
      examiners measured all models once using the calipers only. Validity for the
      widths of individual teeth, the mean tooth width and the Bolton ratios were
      assessed using a general linear model two-way analysis of variance and pair-wise
      comparisons between the two digital methods and the calipers. Reliability was
      assessed with Cronbach's alpha and reproducibility with the intra-class
      correlation coefficient. RESULTS: There were statistically significant
      differences between the tooth widths measured with DigiModel and the calipers (p
      < 0.001) and with the calipers and digital photographs (p < 0.001). However these
      discrepancies were judged not to be clinically significant. The Cronbach's alpha
      scores for all methods were classified as 'excellent'. The intra-class
      correlation coefficient values exceeded 0.75 for the digital calipers, 0.79 for
      DigiModel and 0.54 for the digital photographs. CONCLUSIONS: The validities of
      DigiModel and digital photographs for tooth width measurements and Bolton
      analyses are clinically acceptable. The reliability of both methods is also
      excellent. However, DigiModel software provided more accurate Bolton's ratios and
      demonstrated greater reproducibility than the digital photographs.

PMID- 20043543
TI  - Stresses around a miniscrew. 3-D analysis with the finite element method (FEM).
AB  - BACKGROUND: Miniscrews used for absolute anchorage may induce stresses in the
      surrounding tissues that are dependent on their proximity to the miniscrew. AIMS:
      To determine the stresses in the buccal walls of the sockets of lower molars
      adjacent to a miniscrew under load when the position and angulation of the
      miniscrew are changed. METHODS: Five 3-D FEM models containing the first and
      second lower molars, their periodontal ligaments and the surrounding spongy and
      cortical bone, were modelled in SolidWorks 2006 (SolidWorks, Concord, MA, USA)
      and transferred to the ANSYS Workbench (ANSYS Inc., Southpointe, Canonsburg, PA,
      U.S.A.). A tensile force of 2 N, decomposed in 3-D space, was applied to a
      miniscrew inserted between the lower first and second molars. The von Mises
      (equivalent) stresses along the buccal walls of the sockets of the first and
      second molars were derived following changes in miniscrew position and
      angulation. No direct force was applied to the molars. RESULTS: When the
      miniscrew was inserted at right angles to the bone and midway between the molars
      the stress in the crestal area was 0.093 MPa. This stress increased
      proportionally in the first molar socket as the miniscrew was moved towards the
      first molar and declined when the miniscrew was tipped towards the second molar.
      Stresses also decreased in the crestal area of the second molar as the miniscrew
      was moved towards the first molar, but increased when it was tipped towards the
      second molar. A 30-55 per cent increase in crestal stress in the first molar
      socket was detected. CONCLUSION: Stress occurred in the tissues surrounding a
      miniscrew subjected to a force vector. Changes in the position or angulation of a
      miniscrew can affect the stress in the socket walls of adjacent teeth.

PMID- 20043544
TI  - Perception of pain and discomfort during tooth separation.
AB  - OBJECTIVES: To evaluate patients' perceptions of pain and discomfort during tooth
      separation and to compare the effectiveness of brass wire and elastomeric
      separators. METHODS: The participants were 87 adults with a mean age of 22.1 +/-
      1.9 years. Elastomeric and brass wire separators were inserted mesial and distal
      to upper right (elastomeric separators) and upper left first molars (brass wire
      separators) in each subject. After seven days, the amount of tooth separation was
      measured with a leaf gauge, and pain perception and discomfort were evaluated
      with a visual analogue scale and questionnaire. RESULTS: The elastomeric
      separators produced significantly more separation than the wire separators. There
      was a statistically significant difference in the subjects' perceptions of pain
      and discomfort at rest and during chewing between the different separators (p <
      0.001). In general, the brass wire separators caused the greatest pain and
      discomfort immediately after insertion. Pain from the wire separators subsided
      over seven days, whereas elastomeric separators caused the greatest pain on the
      first two days after insertion. Eating was negatively influenced by the
      separation in 61 per cent of the subjects on the first day. On the other hand,
      other daily activities were affected minimally. CONCLUSIONS: The different levels
      of pain and discomfort caused by these separators, together with their advantages
      and disadvantages, can help the clinician to choose an appropriate separator.
      Patients should be warned that pain due to separation may affect their chewing,
      social life, school work and sleeping. Analgesics and soft food are recommended
      following placement of separators.

PMID- 20043545
TI  - Changes in soft tissue profile and electromyographic activity after activator
      treatment.
AB  - BACKGROUND: To date, few studies have correlated the changes in muscle activity
      and specific soft tissue variables in adolescents with malocclusions. OBJECTIVE:
      To determine associations between the soft tissue profile and electromyographic
      activities in temporalis, masseter and orbicularis oris muscles in children with
      Class II division 1 malocclusions treated with activators. METHODS: For this
      prospective study, 25 subjects with Class II division 1 malocclusions were
      randomly assigned to either a Treatment group (N=15) or a Control group (N=10).
      The mean skeletal ages of the subjects in the Treatment and Control groups were
      11.3 +/- 1.1 and 11.0 +/- 1.3 years, respectively. The subjects in the Treatment
      group were treated with activators and the subjects in the Control group were
      untreated. Lateral cephalometric radiographs and EMG recordings of the anterior
      temporalis and masseter muscles during clenching, chewing and swallowing and the
      orbicularis oris muscle during whistling were obtained at the start of the study
      and 12 months later. Changes in the soft tissue profile were correlated with
      changes in the EMG activities in anterior temporalis, superficial masseter and
      orbicularis oris muscles. RESULTS: The upper lip to E line distance (UL-E)
      decreased more in the Treatment group than the Control group (p < 0.05) and the H
      angle decreased in the Treatment group, but increased in the Control group (p <
      0.01). The EMG activities of temporalis and masseter muscles increased
      significantly in both groups. All between-group EMG differences were
      statistically significant with the exception of the activities in the temporalis
      and masseter muscles during swallowing. In the Treatment group, a significant
      positive correlation (r = .57) was found between the changes in UL-E and anterior
      temporalis activity during swallowing, and significant negative correlations were
      observed between the EMG activity of masseter muscle during swallowing and
      changes in LL-E (r = -.54), OLp-UL (r = -.55) and OLp-LL (r = -.67). CONCLUSIONS:
      Activator therapy is accompanied by changes in the lips and temporalis and
      masseter activities during swallowing.

PMID- 20043546
TI  - Effect of in vivo aging on the shear bond strength of an orthodontic adhesive.
AB  - AIMS: To assess the effect of intra-oral aging on the shear bond strength of a
      composite resin orthodontic adhesive (Transbond XT, 3M Unitek, Monrovia, CA, USA)
      after 6 months in the oral cavity and to compare it with control specimens not
      subjected to intra-oral aging. METHODS: The sample consisted of patients aged 13
      36 years, in need of premolar extractions for orthodontic purposes. Ten premolars
      were bonded with Transbond XT. After 6 months in vivo, the teeth were carefully
      extracted, sectioned at the amelo-cemental junction, mounted in cold cure acrylic
      resin cylinders and subjected to shear bond strength testing using a universal
      testing machine. The debonded bracket base surfaces were then studied under light
      microscope, photographed digitally and analysed with SigmaScan Image Measurement
      Software (Jandel GmbH, Erkrath, Germany) for the percentage of coverage of the
      debonded brackets with the orthodontic adhesive. The same procedure was followed
      for 14 premolars from the same patients bonded in vitro with the same adhesive.
      RESULTS: No statistically significant differences were found in the shear bond
      strength between the two groups of composite resin adhesive systems (with and
      without clinical aging) or in the adhesive remnant coverage following debonding.
      No significant correlation was detected between the shear bond strength and the
      adhesive remnant coverage in the test specimens with and without aging.
      CONCLUSIONS: Laboratory studies of shear bond strength appear to be clinically
      relevant.

PMID- 20043547
TI  - Bond failure in clinical practice.
AB  - BACKGROUND: It has been suggested that the small bonding pads and prominent
      profiles of self-ligating brackets may lead to high failure rates when compared
      with conventional edgewise brackets. AIMS: To compare the bond failure rates of a
      self-ligating bracket (Speed, Strite Industries, Cambridge, Canada) and a twin
      edgewise bracket (Mini-Diamond, Ormco, Orange, CA, U.S.A.) bonded with different
      adhesives (Sequence, Ormco, Orange, CA, U.S.A.; Transbond XT, 3M Unitek,
      Monrovia, CA, U.S.A.); to compare the bond failure rates of a self-ligating
      bracket bonded with different adhesives (Enlight, Ormco, Orange, CA, U.S.A.;
      Lightbond, Reliance, Itasca, IL, U.S.A.); and to compare the bond failure rates
      of molar attachments (Speed, Strite Industries, Cambridge, Canada) using
      different adhesives (Enlight, Ormco, Orange, CA, U.S.A.; Lightbond, Reliance,
      Itasca, IL, U.S.A.; Sequence, Ormco, Orange, CA, U.S.A.; Transbond XT, 3M Unitek,
      Monrovia, CA, USA). METHODS: This retrospective study covered 17 years. Study A
      (1991-99): Speed and Mini-Diamond brackets were bonded in both arches with either
      Sequence (Group 1) or Transbond-XT (Group 2) adhesives and the number of bond
      failures compared. Study B (2000-07): Speed brackets were bonded with either
      Lightbond (Group 3) or Enlight (Group 4) adhesives and the total number of bond
      failures (first-time and re-failures) compared. In Study C (1991-2007) Speed
      upper molar mini-brackets, upper molar tubes or ER brackets were used in the
      upper arch, and Speed lower buccal tubes were used in the lower arch. The failure
      rates of the molar attachments were compared. RESULTS: In Study A the failure
      rates with Sequence adhesive were: Speed 7.3 per cent, Mini-Diamond 11.9 per cent
      (p = 0.05). With Transbond XT adhesive the failure rates were: Speed 5.9 per
      cent, Mini-Diamond 6.4 per cent (p > 0.05). The teeth with the highest failure
      rates (central incisors and second premolars) were similar for both appliances.
      In Study B the failure rates were: Group 3 (Speed/Lightbond) 4.2 per cent; Group
      4 (Speed/Enlight) 6.9 per cent; Group 3 vs Group 4, p = 0.05. In Study C the
      failure rate of Speed upper molar mini-brackets was markedly higher than the
      failure rates of the molar tubes. CONCLUSIONS: The failure rates of the Speed
      brackets reduced over time, possibly because of improvements in the adhesives.
      The small bonding pads and prominent profiles of Speed brackets did not result in
      high failure rates.

PMID- 20043548
TI  - Static frictional resistance with the slide low-friction elastomeric ligature
      system.
AB  - AIM: This ex-vivo study compared the static frictional resistance of a low
      friction ligation system against a conventional elastomeric module, and studied
      the effect of storage in a simulated oral environment on the static frictional
      resistance of both ligation systems. METHODS: Eighty stainless steel brackets
      were tested by sliding along straight lengths of 0.018 inch round and 0.019 x
      0.025 inch rectangular stainless steel wires ligated with either conventional
      elastomerics or the Slide system (Leone, Florence, Italy). During the tests the
      brackets and wires were lubricated with artificial saliva. A specially
      constructed jig assembly was used to hold the bracket and archwire securely. The
      jig was clamped in an Instron universal load testing machine. Crosshead speed was
      controlled via a microcomputer connected to the Instron machine. The static
      frictional forces at 0 degree bracket/wire angulation were measured for both
      systems, fresh from the pack and after storage in artificial saliva at 37 degrees
      C for 24 hours. RESULTS: The results of this investigation demonstrated that the
      Slide ligatures produced significantly lower static frictional resistance than
      conventional elastomeric modules in the fresh condition and after 24 hours of
      storage in a simulated oral environment (p < 0.001). Storage for 24 hours in
      artificial saliva had no effect on the static frictional resistance of
      conventional elastomeric modules and the Slide system (p = 0.525). CONCLUSIONS:
      The claim by the manufacturer that the Slide system produces lower frictional
      resistance than conventional elastomeric modules is upheld.

PMID- 20043549
TI  - Gingival health and relapse tendency: a prospective study of two types of lower
      fixed retainers.
AB  - BACKGROUND: Different types and diameters of wire are used in bonded lingual
      retainers. Some clinicians bond a small diameter multistrand wire to each tooth,
      while other clinicians bond a large diameter wire to the lingual surfaces of the
      lower canines. AIM: To compare the gingival health, plaque accumulation, tooth
      stability and integrity of multistrand wire and round wire bonded lingual
      retainers. METHODS: Sixty-two subjects, who had completed treatment and who
      required fixed retention for the lower anterior segment, were assigned to either
      the Round wire retainer group or the Multistrand wire retainer group. In the
      Round wire retainer group, a 0.036 inch round, stainless steel wire was bonded to
      the lingual surfaces of both lower canines. The Multistrand retainer group had a
      0.015 inch multistrand wire bonded to the lingual surfaces of all lower anterior
      teeth. At least 12 months after debonding, the subjects were recalled and the
      following variables were recorded: Oral Hygiene Index (OHI), Plaque Index (PI) of
      the lower anterior teeth, Gingival Index (GI) of the lower anterior teeth,
      Irregularity Index (IRI) of the lower anterior teeth, and the number of broken
      retainers. RESULTS: There were no significant differences between the PI (p =
      0.165) and GI (p = 0.150) of the two groups. More plaque was found on the distal
      surfaces of the lower anterior teeth in the group with multistrand wire retainers
      (p = 0.02). The lower anterior teeth were significantly more irregular in the
      group with round wire retainers compared to the group with multistrand wire
      retainers (p = 0.002). Although the multistrand wire retainers fractured more
      frequently than the round wire retainers the difference was not statistically
      significant (p = 0.325). CONCLUSION: More plaque accumulated on the distal
      surfaces of the lower anterior teeth in subjects with multistrand wire retainers
      than in subjects with round wire retainers. Multistrand wire retainers were
      better at maintaining incisor alignment than single span, round wire retainers.

PMID- 20043550
TI  - Clinical investigation of periodontal ligament distraction osteogenesis for rapid
      orthodontic canine retraction.
AB  - AIMS: To investigate rapid canine distalisation by periodontal ligament
      distraction and to determine the effects of periodontal ligament distraction on
      the canine root and pulpal vitality. METHODS: The sample consisted of 16 upper
      canines in eight patients who required first premolar extractions. The upper
      first premolars were extracted and the interseptal bone distal to each canine was
      thinned and undermined surgically. Custom-built distractors were placed and
      activated immediately to distract the canines into the extraction spaces.
      Radiographs were taken before canine distraction and at regular intervals
      thereafter. The upper canine pulps were tested with an electronic pulp tester
      before and after the distraction and the canines were examined on the post
      distraction radiographs for evidence of apical and lateral root resorption.
      RESULTS: The canines were retracted to proximal contact with the second premolars
      in 20.33 +/- 1.87 days. The average amount of retraction was 5.25 mm and the
      canines tipped distally 15.33 degrees. Although the upper molars did not move
      mesially, they extruded almost 1 mm. Root resorption was minimal and there was no
      deterioration in pulp vitality. CONCLUSION: Canines can be rapidly retracted by
      periodontal ligament distraction without complications. However, the efficacy of
      the method depends upon the surgical procedure, which is technique sensitive.
      Resistance offered by the interseptal bone distal to the apex of the canine was
      thought to be the reason for the canine tipping during distraction.

PMID- 20043551
TI  - Changes in shear bond strength of ceramic and stainless steel brackets with
      different visible light curing times and directions.
AB  - BACKGROUND: Selection of the appropriate curing time and light direction may
      enable the appropriate shear bond strength to be obtained and avoid enamel
      fracture during debonding. AIMS: To determine the effects of different curing
      times and light directions on the shear bond strengths of ceramic and stainless
      steel brackets. METHOD: Ninety-two recently extracted, upper premolars were
      randomly assigned to six groups. Either stainless steel or ceramic brackets were
      bonded to the buccal surfaces of the teeth. Group I, stainless steel brackets
      cured for 40 seconds from buccal surface; Group II, stainless steel brackets
      cured for 40 seconds from palatal surface; Group III, stainless steel brackets
      cured for 80 seconds from palatal surface; Group IV, ceramic brackets cured for
      40 seconds from the buccal surface; Group V, ceramic brackets cured for 40
      seconds from the palatal surface; Group VI, ceramic brackets cured for 80 seconds
      from the palatal surface. The shear bond strength was measured with a universal
      testing machine and the resin remaining after debonding scored with the Adhesive
      Remnant Index (ARI). The data were analysed with the oneway ANOVA, Tukey's HSD
      test and the Kruskal-Wallis test. Associations between the ARI and shear bond
      strength were determined with Pearson's correlation coefficient. RESULTS: Group
      IV (ceramic brackets cured for 40 seconds from buccal surface) had the highest
      shear bond strength (21.26 MPa) and Group II (metal brackets cured for 40 seconds
      from palatal surface) had the lowest shear bond strength (6.95 MPa).There was no
      significant difference in ARI scores among the groups. The association between
      the ARI scores and bond strength values was not statistically significant.
      CONCLUSIONS: Curing from the buccal surface for 40 seconds gave unacceptably high
      shear bond strength values for both stainless steel and ceramic brackets. Lower
      shear bond strengths occurred when the light was directed from the palatal
      surface, but a shorter curing time is more likely to be preferred by clinicians.
      Future studies should investigate the possibility of reducing the curing time for
      both brackets.

PMID- 20043552
TI  - Facial asymmetry in subjects with class III malocclusion.
AB  - BACKGROUND: Facial skeletal asymmetries in Class III subjects seeking
      orthognathic surgery may complicate subsequent treatment. OBJECTIVE: The purpose
      of this study was to investigate facial asymmetry in orthognathic surgery
      patients with Class III malocclusion. METHODS: The Class III group consisted of
      29 orthognathic surgery patients 114 female, 15 male; Mean age: 21.44 years) with
      Class III malocclusions. The Control group consisted of 32 subjects (16 female,
      16 male; Mean age: 19.20 years) with excellent Class I occlusal relationships.
      Facial skeletal asymmetry, based on the skeletal midline, was measured on
      posteroanterior radiographs. In the Class III group, the chin point deviated to
      the ipsilateral side. The side-to-side and between group differences were
      compared. RESULTS: In the Class III group, the antegonial notch--skeletal midline
      distance was significantly larger (p < 0.05) and menton-antegonial notch distance
      was significantly different (p < 0.05). There were no statistically significant
      differences between the right and left side measurements in the Control group.
      Between-group comparisons showed that subjects in the Class III group had greater
      skeletal asymmetries in lower face. In 78 per cent of the subjects in the Class
      III group the chin point was displaced more than 2 mm to one side. CONCLUSIONS:
      Subjects with Class III malocclusion may have facial skeletal asymmetries,
      predominantly in the lower face. Frontal asymmetries should be considered during
      diagnosis and treatment planning.

PMID- 20043553
TI  - Variations in tooth size and arch dimensions in Malay schoolchildren.
AB  - AIMS: To compare the mesio-distal tooth sizes and dental arch dimensions in Malay
      boys and girls with Class I, Class II and Class III malocclusions. METHODS: The
      dental casts of 150 subjects (78 boys, 72 girls), between 12 and 16 years of age,
      with Class I, Class II and Class III malocclusions were used. Each group
      consisted of 50 subjects. An electronic digital caliper was used to measure the
      mesio-distal tooth sizes of the upper and lower permanent teeth (first molar to
      first molar), the intercanine and intermolar widths. The arch lengths and arch
      perimeters were measured with AutoCAD software (Autodesk Inc., San Rafael, CA,
      U.S.A.). RESULTS: The mesio-distal dimensions of the upper lateral incisors and
      canines in the Class I malocclusion group were significantly smaller than the
      corresponding teeth in the Class III and Class II groups, respectively. The lower
      canines and first molars were significantly smaller in the Class I group than the
      corresponding teeth in the Class II group. The lower intercanine width was
      significantly smaller in the Class II group as compared with the Class I group,
      and the upper intermolar width was significantly larger in Class III group as
      compared with the Class II group. There were no significant differences in the
      arch perimeters or arch lengths. The boys had significantly wider teeth than the
      girls, except for the left lower second premolar. The boys also had larger upper
      and lower intermolar widths and lower intercanine width than the girls.
      CONCLUSION: Small, but statistically significant, differences in tooth sizes are
      not necessarily accompanied by significant arch width, arch length or arch
      perimeter differences. Generally, boys have wider teeth, larger lower intercanine
      width and upper and lower intermolar widths than girls.

PMID- 20043554
TI  - The interaction of function and stability in the dentition.

PMID- 20043555
TI  - Clinical correlates of pain with second-trimester genetic amniocentesis.
AB  - OBJECTIVE: To determine the correlation of clinical factors and maternal
      perceptions of pain with genetic amniocentesis. MATERIAL AND METHOD: This
      prospective study of midtrimester, singleton pregnancies was conducted between
      February 2007 and March 2008. Study variables included patient dermographics,
      previous amniocentesis, previous abdominal surgery, maternal anxiety score,
      abdominal wall thickness, needle insertion through placenta and the depth of
      needle insertion. Maternal pain with performing amniocentesis was subjectively
      quantified with the Thai short-form McGill Pain Questionnaire. The independent T
      test, one way ANOVA and linear regression were used for analysis, a probability
      value of < 0.05 was considered significant. RESULTS: One hundred and twenty-five
      pregnant women participated in the present study: 18.4% reported no pain, 69.6%
      described the pain as mild, 11.2% described the pain as discomforting and 0.8%
      described the pain as horrible. Mean intensity of pain was 2.1 +/- 1.9 (on a
      scale 0-10). Pain was most often described as fearful, shooting, throbbing and
      sharp. Parity, gestational age, maternal BMI, anxiety score, previous surgery,
      needle insertion through the placenta, abdominal wall thickness and the depth of
      needle insertion were not correlated with perceived pain. CONCLUSION: Most of the
      women reported no pain or mild or discomfort with genetic amniocentesis. Clinical
      factors were not associated with maternal perceptions of pain.

PMID- 20043556
TI  - Comparison of success rate and complications of contour-loop excision of the
      transformation zone (C-LETZ) with cold knife conization (CKC) in high grade
      lesion (HGL) from colposcopic impression.
AB  - OBJECTIVE: To compare the complications and success rate of Contour-Loop Excision
      of the Transformation Zone (C-LETZ) with Cold Knife Conization (CKC) in High
      Grade Lesion (HGL). MATERIAL AND METHOD: Between April 1st, 2007 and November
      30th, 2007, forty-five C-LETZs were performed in patients who had Pap smear
      result of High grade Squamous Intraepithelial Lesion (HSIL) or Squamous Cell
      Carcinoma (SCC) combined with colposcopic impression of satisfactory HGL by using
      the "See and Treat" approach. Success rate, tissue size, operating time, blood
      loss, intra-operative, and post-operative complications (2 weeks) were recorded
      to compare with the retrospective results from therapeutic CKC. RESULTS: Forty
      five cases of C-LETZ and 50 cases of CKC were compared. Using the "See and Treat"
      approach, the over-treatment rate was 6.7% (3/45). The success rate and tissue
      size were not different between both groups. The operating time, blood loss, and
      post-operative infection were significantly less in the C-LETZ group. CONCLUSION:
      The authors compared CKC with C-LETZ, which is a new method for the management
      ofHGL of the cervix and found C-LETZ to be a favorable method with comparable
      efficacy but with significantly less morbidity, and suitable as a "See and Treat"
      method in a hospital outpatient clinic.

PMID- 20043557
TI  - Fractional thigh volume by three-dimensional ultrasonography for birth weight
      prediction.
AB  - OBJECTIVE: To determine the correlation between actual birthweight (BW) and fetal
      weight calculated from fractional thigh volume (ThiV). MATERIAL AND METHOD: The
      authors have conducted a prospective, cross-sectional study of normal Thai fetal
      thigh volume. There were 176 eligible pregnant women who met the criteria of
      singleton with no fetal anomaly were recruited into the present study. Prior to
      the present study, 3 operators had been trained and standardized for fractional
      ThiV measurement by an expert for the first 20 cases. To generate the fetal
      weight calculating formula, fetal ThiV data from the first 100 cases were
      employed Then, the authors' new prediction formula was compared and validated
      with the Hadlock's and the Tongsong formula in 56 normal late-third-trimester
      fetuses. All patients were assessed for 2D fetal biometry and 3D fractional ThiV
      within one week before delivery. RESULTS: A total of 176 fetuses underwent
      ultrasound at the gestational age of 38.5 +/- 2.1 weeks. The reproducibility of
      fractional ThiV measurement technique showned very good correlation in both inter
      and intra-observer reliability as observed by the high intraclass correlation
      (0.971-0.994). By using the regression model, fractional ThiV presents a superior
      correlation to actual BW (r = 0.965). The fitting formula is characterized by
      predicted fetal BW (g) = 774.744 + 32.658 x fractional ThiV (ml). The presented
      new formula shows the smallest absolute percentage error (APE) for BW estimation
      when compared to that of Hadlock's and Tongsong's. CONCLUSION: Fetal 3D
      fractional ThiV is consistent with actual BW The measurement of fractional ThiV
      can improve the accuracy of fetal weight prediction especially in some eventful
      conditions.

PMID- 20043558
TI  - Risk factors for primary postpartum hemorrhage in Bhumibol Adulyadej Hospital.
AB  - BACKGROUND: Postpartum hemorrhage remains one of the main causes of maternal
      morbidity and mortality in both developed and developing countries. Hemorrhages
      account for 28%of all direct maternal deaths and remain the most common cause of
      direct maternal deaths worldwide. OBJECTIVE: To study the incidence and risk
      factors for postpartum hemorrhage (PPH) in Bhunibol Adulyadej Hospital. MATERIAL
      AND METHOD: Retrospective cohort study of 19,429 patients who gave birth between
      P' January 2004 and 31st December 2007 at Bhumibol Adulyadej Hospital. One
      thousand five hundred and thirty women were enrolled in the present study, three
      hundred and eighty five women had postpartum hemorrhage and one thousand one
      hundred and forty-five had no postpartum hemorrhage. The present study analyzed
      one postpartum hemorrhage woman compared to three women who gave birth in nearly
      the same period and had no postpartum hemorrhage both vaginal deliveries and
      cesarean section. RESULTS: The PPH rate in Bhumibol Adulyadej Hospital was 1.98%.
      Maternal age, height and fetal birth weight were not different between the PPH
      group and no PPH group. The strongest risk factors for postpartum hemorrhage in
      the present study were prolonged 3rd stage of labor, retained placenta,
      lacerations of birth passage, and placenta previa. CONCLUSION: The strongest risk
      factors for postpartum hemorrhage in the present study were prolonged 3rd stage
      of labor, retained placenta, lacerations of birth passage, and placenta previa.

PMID- 20043559
TI  - Feasibility and safety of intra-coronary bone marrow mononuclear cell
      transplantation in ST elevation myocardial infarction patients.
AB  - BACKGROUND: Stem cell transplantation is a potential treatment to improve left
      ventricular ejection fraction (LVEF) after ST elevation myocardial infarction
      (STEMI). However technique and mode of transplantation, type of cells, number of
      cells, and when to transplant are still unknown. OBJECTIVE: To determine the
      feasibility and safety of bone marrow mononuclear cell (BMC) intra-coronary
      transplantation and 6-months results in patients with STEMI. MATERIAL AND METHOD:
      After successful percutaneous coronary intervention (PCI) in STEMI patients who
      did not have flow re-established within 12 hours and poor LVEF (less than 50%) by
      echocardiography were enrolled Bone marrow aspiration of 100 cc was performed in
      the morning. After cell processing for 3 hours, the suspension of BMC about 10 cc
      were infused to infarcted area using standard PCI technique. Balloon occlusion
      for 3 minutes was performed during cell infusion. Cardiac magnetic resonance
      imaging was used to determine LVEF scar volume and LV volume before and 6 months
      after transplantation. RESULTS: Five patients were enrolled between May and
      August 2006. Duration of STEMI before transplantation ranged from 18 days to 14
      years. Total amount of BMC ranged from 67 x 10(6) to 335 x 10(6). Number of CD 34
      and CD 133+ cells were approximation to be 0.7 x 10(6) to 7.7 x 10(6) and 0.01 x
      10(6) to 3.04 x 10(6). LVEF was increased from 36.4 at baseline to 43.3 at 6
      month. NT pro-BNP level was decreased from 1105 ng/ml at baseline to 288 pg/ml at
      6-month. No complications such as chest pain, no re-flow phenomenon, ventricular
      arrhythmia, or hypotension was detected during the procedure. CONCLUSION: Intra
      coronary BMC transplantation in patients with STEMI in our center is feasible and
      safe. LVEF was slightly improved; however, a randomized controlled study is
      needed.

PMID- 20043560
TI  - Prevalence of CYP2C9 and VKORC1 mutation in patients with valvular heart disease
      in northern Thailand.
AB  - BACKGROUND: Warfarin has been widely used for the prevention and treatment of
      thromboembolism. Warfarin therapy depends on interaction between physiological,
      environmental, and genetic factors. Vitamin K epoxide reductase (VKORC1) and
      cytochrome P450 2C9 (CYP2C9) enzyme conjointly determine the warfarin maintenance
      dose. The prevalence of CYP2C9 and VKORC1 variants varies among ethnic groups.
      The purpose of the present study was to investigate the prevalence of CYP2C and
      VKORC1 in the Northern Thai population. MATERIAL AND METHOD: Patients with
      valvular heart disease who regularly took a steady maintenance warfarin dose for
      at least one month were recruited into the present study. Patients who had taken
      amiodarone or an anti-inflammatory drug were excluded Clinical data were obtained
      from medical records. Five milliliters of whole blood was drawn from each patient
      for gene analysis and prothrombin time with international normalized ratio (INR)
      measurement. RESULTS: From 242 patients, CYP2C9 *1/*1 was found in 230 patients
      (95%) and CYP2C9 *1/*3 was found in 12 patients (5%). Neither mutant CYP2C9*2
      allele nor individuals homozygous for CYP2C9*3 were observed. Regarding VKORC1,
      haplotype AB was found in 83 patients (34.3%) and haplotype AA was found in 154
      patients (63.6%). Haplotype BB (wild type) was found in five patients (2.1%).
      CONCLUSION: The prevalence of CYP2C9 *1/*1 is high while the prevalence of
      CYP2C9*2 and CYP2C9*3 is very low. VKORC1 haplotype AA is the most common among
      the Northern Thai population. Further study regarding pharmacogenetic and non
      genetic factors to develop warfarin-dosing algorithm is warranted

PMID- 20043561
TI  - The quality of life of stroke outpatients at Srinagarind Hospital.
AB  - BACKGROUND: Stroke, a disease of the cerebral blood vessels, is known as
      paralysis disease in Thailand and is a major public health problem. Stroke is a
      chronic disease with a lengthy development, leading to a paralytic state in which
      the patient faces obstacles doing his/her daily routine and needs to depend upon
      others. Expenses are for both in hospital treatment and homecare. A study on the
      quality of life of stroke outpatients was conducted in order to plan assistance
      to patients, both at the family and health service unit level. The present study
      represents the first of its kind performed at Srinagarind Hospital. OBJECTIVE: To
      study the quality of life of stroke outpatients at Srinagarind Hospital. STUDY
      DESIGN: Descriptive research. MATERIAL AND METHOD: A questionnaire was
      constructed by the researchers, the content and methodology of which was checked
      by experts. The first section collects personal information and the second the
      quality of life using the SF-36 rating scale, which has been used on many chronic
      patients in ten different countries and both the English and Thai versions who
      have undergone validity testing. RESULTS: The stroke outpatients were between 20
      and 91 years of age (mean, 64 +/- 12.8). Most (31.6%) were diagnosed with
      cerebral infarction, with a Modified Rankin Score of 1. Concurrent diseases
      included hypertension, dyslipidemia and diabetes, respectively. The quality of
      life was relatively good in all tested aspects. The highest scoring category was
      mental health and role emotional, which accounted for 69.5 and 68.0 percentage,
      respectively. The worst two categories reported were vitality and general health,
      both accounting for 60.0%, which had an impact on self esteem, exacerbated if the
      patients felt tired, exhausted and/or believed their lives were becoming worse.
      CONCLUSION: The present study can be used to improve the management of stroke out
      patient services. It is recommended that a healthcare team be set up at the
      hospital clinic to provide assistance for dealing with both feelings and
      emotions.

PMID- 20043562
TI  - A comparison of early postoperative results between urgent closed
      hemorrhoidectomy for prolapsed thrombosed hemorrhoids and elective closed
      hemorrhoidectomy.
AB  - OBJECTIVE: To compare the perioperative complications, analgesics requirement,
      and length of hospital stay between patients undergoing urgent closed
      hemorrhoidectomy for prolapsed thrombosed hemorrhoid and elective closed
      hemorrhoidectomy. RESEARCH DESIGN: Retrospective, comparative study. MATERIAL AND
      METHOD: All records of the patients who underwent urgent and elective
      hemorrhoidectomy between January 2000 and December 2005 were reviewed.
      Perioperative complications (bleeding, urinary retention, post-operative
      thrombosis, and wound dehiscence), analgesic requirement, and length of hospital
      stay were analyzed. STATISTICS: Chi-Square Test and Mann-Whitney U Test. RESULTS:
      From 1440 patients, 1184 patients met the inclusion criteria. All were done with
      closed technique. The indication for urgent hemorrhoidectomy was prolapsed
      thrombosed hemorrhoid in 416 patients (group 1). The indication for elective
      hemorrhoidectomy were grade 3 and 4 internal hemorrhoid, external hemorrhoid or
      combined hemorrhoid in 768 patients (group 2). There was no statistically
      significant difference in urinary retention and bleeding complication between two
      groups; 31 patients (7.5%) in group 1 and 69 patients (8.9%) in group 2
      experienced urinary retention p = 0.426, five patients (1.2%) in group 1 and 10
      patients (1.3%) in group 2 had postoperative bleeding, p = 1.000). On the second
      postoperative week, wound dehiscence was found in nine patients (2.2%) from group
      1 and 15 patients (2%) from group 2. On the fourth week, all the wounds were
      completely healed without granulation or stricture formation. Post-operative
      meperidine requirement was significantly lower in the urgent hemorrhoidectomy
      group (0.84 +/- 0.71 vs. 0.99 + 0.81 mg/kg, p < 0.001). Post-operative length of
      hospital stay were not statistically different (1.017 +/- 0.129 vs. 1.016 +/-
      0.124, p = 0.107). CONCLUSION: Urgent closed hemorrhoidectomy for prolapsed
      thrombosed hemorrhoids may be a preferable option for patients suffering from
      this condition.

PMID- 20043563
TI  - Effect of bowel preparation with oral sodium phosphate on serum potassium level
      in patients undergoing colonoscopy under IV anesthesia.
AB  - OBJECTIVE: To determine the effect of oral sodium phosphate solution, as a colon
      preparation agent, on the serum potassium level in patients undergoing
      colonoscopy under IV anesthesia. MATERIAL AND METHOD: Patients set to undergo
      elective colonoscopy under IV anesthesia (propofol infusion) were recruited to
      participate in the present study during the period between October 2008 and
      January 2009. All patients had normal serum potassium level prior to colon
      preparation, and all ingested 90 ml of sodium phosphate solution one day before
      colonoscopy. Blood samples for post preparation potassium level determination
      were taken immediately before administering IV propofol. Baseline data including
      age, gender, diagnosis, indication for colonoscopy, underlying illness,
      concurrent medications and serum potassium and creatinine levels were recorded
      The serum potassium levels were compared before and after colon preparation, and
      potentially important baseline risk factors for low potassium levels after colon
      preparation were determined. RESULTS: In 48 patients, there was a 0.57 mmol/L
      (from 4.11 to 3.54 mmol/L) average reduction in the serum potassium level after
      colon preparation. There were no significant adverse events during colonoscopy.
      No significant risk factors were identified on multivariable linear regression
      analysis. CONCLUSION: There was a mild reduction in serum potassium level after
      colon preparation with oral sodium phosphate solution, which was probably not
      clinically significant. Prophylactic potassium supplement or routine serum
      potassium monitoring after oral sodium phosphate colon preparation did not seem
      to be necessary for this group of patients.

PMID- 20043564
TI  - Reduction in bacteremia rates after rectum sterilization before transrectal,
      ultrasound-guided prostate biopsy: a randomized controlled trial.
AB  - OBJECTIVE: To determine the efficacy of rectum sterilization before TRUS guided
      prostate biopsy in order to decrease bacteremia rate and sepsis complication.
      MATERIAL AND METHOD: From August 2008 to March 2009, 100 volunteers who had an
      indication for prostate biopsy were recruited into the present study in a
      randomized controlled trial. The present study was approved by the Ethics
      Committee on Human Experimentation of Ramathibodi Hospital Faculty of Medicine,
      Mahidol University. The volunteers received unison enema one day before and
      Ciprofloxacin 500 mg 0.5-1 hr before the procedure. These 100 volunteers were
      divided into two groups; 50 were randomly assigned in the group of rectum
      cleaning with 10% povidone-iodine, whereas the other 50 volunteers were placed in
      the control group. Twelve cores of TRUS guided prostate biopsy were performed
      After the procedure, peripheral blood samples were taken for cultures for aerobic
      and anaerobic bacteria. A clinical follow-up at 48-72 hrs after the procedure was
      done via telephone. RESULTS: Hemocultures were positive for 9 cases in the rectum
      cleaning group and 2 cases in the control group (p = 0.025). Three volunteers
      (one in the rectum cleaning group and two in the control group) had a
      postoperative fever but it spontaneously resolved. Two volunteers in the control
      group came back to the hospital because of urinary tract infections and rectal
      bleeding. None of the volunteers had clinical sepsis or went to other hospitals.
      CONCLUSION: Sterilization of the rectum before TRUS guided prostate biopsy was
      found to reduce postoperative bacteremia and might reduce clinical infections.

PMID- 20043565
TI  - The impact of closed ICU model on mortality in general surgical intensive care
      unit.
AB  - BACKGROUND: A closed model oflCU (intensive care unit) care is associated with
      improved outcomes and less resource utilization in mixed medical and surgical
      ICUs as well as traumatic ICUs. However most of ICUs in developing countries use
      an opened model especially in surgical ICUs due to lack of specialized physician.
      The aims of the present are to compare the effects of closed and opened model on
      ICU mortality and length of ICU stay. MATERIAL AND METHOD: The authors conducted
      a retrospective study to compare mortality between two periods of time. First
      period was between July 2002 and June 2004, and used open model. The second
      period was between July 2004 and June 2006, and followed by closed model. The
      closed model was defined as an ICU service led and managed by an intensivist. The
      open model was an ICU service where critically ill surgical patients were managed
      by host surgeons individually. RESULT: Two thousand two hundred and sixty nine
      patients were included in the present (Open vs. Close, 1038 vs. 1231). The
      overall ICU mortality rate was decreased with statistical significance in closed
      model (27.4% vs. 23.4%; p = 0.03). This effect was obvious in patients admitted
      to ICU longer than 48 hours (22.7% vs. 13.9%; p < 0.01). After adjusting for
      differences in baseline characteristics and case-mix factor, the risk of death in
      closed ICU model was also statistically significant less than opened model [RR =
      0.85 (0.74-0.98); p = 0.02]. The effect was explicit in patients admitted to
      ICUlonger than 48 hours [RR = 0.60 (0.47-0. 76); p < 0.01]. However, risk of
      death in non-traumatic patients and elderly patients older than 65 years of age
      tend to be lower in closed model [RR = 0.81 (0.64-1.01); p = 0.06 and RR = 0.81
      (0.64-1.01); p = 0.07 respectively]. In addition, closed model ICU has shorter
      length of ICU stay (5.4 +/- 7.1 vs. 4.6 +/- 6.1 days; p < 0.01) and adjusted
      length of ICU stay was lowered about 0.80 day [-0.80 day (-1.34 to -0.25); p <
      0.01] in closed model with statistical significance when compare to open model.
      CONCLUSION: The closed model, led and managed by an intensivist, is associated
      with reduction in overall ICU mortality and has greatest effect in patients
      admitted longer than 48 hours. Furthermore, this model shortens ICU length ofstay

PMID- 20043566
TI  - Pediatric renal transplantation: a single-center experience in northeast
      Thailand.
AB  - OBJECTIVE: To clarify the demographic data, outcomes and complications of renal
      transplantation in children at Srinagarind (university) Hospital. MATERIAL AND
      METHOD: The authors reviewed the medical records of children with end-stage renal
      disease (ESRD) who received renal transplantation at Srinagarind Hospital, Khon
      Kaen, between August 2001 and July 2008. RESULTS: Eight male and seven female
      patients were identified Their mean age was 12.8 +/- 3.2 years (range, 5.0-17.6).
      The major cause of ESRD was a congenital anomaly of the kidneys (53%). All of the
      children received cadaveric transplantations and none received induction therapy.
      Triple immunosuppressive drugs comprising cyclosporine, prednisolone and
      mycophenolate mofetil were administered to 12 patients. Tacrolimus, instead of
      cyclosporine, was given to three patients who had received a renal transplant
      since January 2008. The median follow-up time was 15 months (3 to 82 months). The
      most frequent complication was urinary tract infection (40%). Acute graft loss
      was found in one patient (6.7%) due to graft infarction. Other complications
      included herpes viral infection, chronic rejection, acute rejection, severe
      gingival hyperplasia, myopathy, lymphocele and transitional cell carcinoma of the
      bladder. Two patients returned to dialysis due to graft infarction and chronic
      rejection, respectively. The mean serum creatinine at the last follow-up of the
      remaining cases was 1.2 +/- 0.5 mg/dL (range, 0.6-2.3). All of the patients
      survived. The 1- and 5-year graft survival rates were 93.3% and 86.7%,
      respectively. CONCLUSION: The present study demonstrates the potential for
      successful outcomes of pediatric renal transplantation in this resource-limited
      area.

PMID- 20043567
TI  - Parents' satisfaction with pediatric ambulatory anesthesia in northeast of
      Thailand.
AB  - OBJECTIVE: Study the satisfaction of parents with ambulatory anesthesia and
      associated factors, including characteristics of the patients and their parents.
      MATERIAL AND METHOD: This was a prospective, descriptive, observation study. The
      authors included children who were scheduled for ambulatory anesthetic service
      between birth and 14 years of age and attended at Srinagarind Hospital, Khon
      Kaen, Thailand. The authors excluded patients whose parents could not be reached
      by telephone. Before anesthesia, the authors recorded the patients and parents'
      characteristics, level of information perception (pre-, peri- and post-anesthesia
      and complications). After anesthesia, the anesthesia technique and any
      complications were recorded. The day after anesthesia, the authors made phone
      calls to the patients to record the parents' satisfaction score (viz, of overall,
      pre-, peri- and post-anesthesia care, and information about the level of patient
      care at home), and any anesthesia related complications. RESULTS: Ninety-two
      patients and their parents were included in the present study. Overall parents
      'satisfaction with the anesthesia service was 96.7% (i.e., 89/92) (95% CI 90.8
      99.3). Parents' satisfaction with pre- and peri-anesthesia care was 100% (95% CI
      96.1-100) and 97.9% (95% CI 92.4-99.7), respectively. Parents' satisfaction with
      the PACU care and information of patient care at home was 96.7% (95% CI 90.8
      99.3) and 91.3% (95% CI 83.6-96.2), respectively. Associated factors where
      parents were dissatisfied included PACU care satisfaction (i.e., relative risk
      22.5 (95% CI 3.2-158)) and patient care information at home (i.e., relative risk
      13.3 (95% CI 1.3-136.0)). CONCLUSION: The present study showed a high level of
      parents' satisfaction. Parents' dissatisfaction associated with PACU care and
      information about post anesthesia care at home. Additionally information on
      parents' characteristics provides invaluable data for improving pediatric
      ambulatory anesthesia in Srinagarind Hospital.

PMID- 20043568
TI  - Success of probing for congenital nasolacrimal duct obstruction in children under
      10 years of age.
AB  - OBJECTIVE: To determine the success of probing for congenital nasolacrimal duct
      obstruction in children aged under 10 years. DESIGN: A retrospective study.
      MATERIAL AND METHOD: The medical records of all children aged under 10 years
      diagnosed with congenital nasolacrimal duct obstruction between 1997 and 2007 who
      underwent probing and irrigation under general anesthesia were reviewed.
      Successful probing was defined as absence of tearing and eye discharge in the
      affected eye at one month or more after treatment. Data obtained included age at
      first visit, gender laterality of the eyes, history of previous probing, age at
      probing time, number of probing, and treatment outcomes. Patients were
      categorized into four groups according to age at treatment (0-1 year, 1-2 years,
      2-3 years and 3-10 years). RESULTS: Forty-four patients were seen during the
      study period, 19 males and 25females, with 29 right eyes and 30 left eyes
      undergoing treatments of 29 unilateral probing and 15 bilateral probing. The age
      at probing ranged from 10 months to 9.6 years (mean +/- SD, 2.51 +/- 1.82 years).
      Successful probing were identified in 47 out of 59 eyes (80%, 95% CI = 67 to
      89%). Most successful eyes required only one probing and only two eyes needed a
      second probing. The success rates were 80% (8/10 eyes) in patients 0-1 year of
      age, 86% (18/21 eyes) in patients 1-2 years of age, 75% (12/16 eyes) in patients
      2-3 years of age, and 75% (9/12 eyes) in patients 3-10 years of age. CONCLUSION:
      The success rate of probing for treatment of congenital nasolacrimal duct
      obstruction varies, depending on the age of the child at treatment. It was higher
      in children under 2 years than in older children.

PMID- 20043569
TI  - Accuracy of 64 sliced multi-detector computed tomography in diagnosis of small
      bowel obstruction.
AB  - OBJECTIVE: The purpose of the present study was to determine the accuracy of 64
      sliced multi-detector computed tomography (MDCT) in the diagnosis of patients
      with suspected small bowel obstruction (SBO) and identify the definite cause of
      SBO for further investigation or treatment. MATERIAL AND METHOD: A retrospective
      study was performed on 35 patients with suspected SBO who underwent 64 sliced
      MDCT to establish the diagnosis and cause of SBO. The patients were enrolled from
      January 1, 2005 to June 30, 2007. The MDCT scan of whole abdomen from patients
      with suspected SBO were retrospectively evaluated by two gastrointestinal
      radiologists without knowledge of the patients history determined the presence or
      absence of SBO, cause, location, small-bowel feces sign, complication (sign of
      associated bowel strangulation), and confident on a five-point scale. Sensitivity
      and specificity estimates with confidence intervals were calculated. Weighted
      kappa statistics were used to estimate agreement between readers. RESULTS: Twenty
      five patients ultimately proved to have SBO, and ten patients had no evidence of
      SBO. The overall sensitivity, specificity, and accuracy of 64 sliced MDCT to
      establish the diagnosis of SBO were 96%, 100%, and 97%, respectively. The final
      diagnosis was established either by surgery (13 patients) or by the clinical
      evolution (12 patients). Causes of SBO included adhesions (n=10), metastases
      (n=4), post-radiative enteropathy (n=1), internal hernia (n=3), ileitis (n=2),
      inguinal hernia (n=1), submucosal hemorrhage (n=1), benign stricture secondary to
      chronic pancreatitis (n=1), midgut volvulus (n=1), and SMA syndrome (n=1). When
      obstructions were classified into low and high grade obstruction, CT results
      could be used to identify correctly 100% (13 of 13) of high grade SBO and 58% (7
      of 12) of low grade SBO. The 64 sliced MDCT yielded one false-negative for
      patients with partial SBO due to adhesion band Small-bowel feces sign was
      detected in 4 of 25 patients, who were diagnosed as SBO. CONCLUSION: The 64
      sliced MDCT is a highly sensitivity and specificity method to diagnose SBO and
      cause of obstruction. The ability of MDCT to show the cause of SBO makes CT an
      important additional diagnostic tool when specific management issues must be
      addressed.

PMID- 20043570
TI  - Three-Tesla MRI diagnosis of meniscal tears of the knee.
AB  - OBJECTIVE: To study and diagnose meniscal tear of the knee using 3-Tesla (3-T)
      magnetic resonance imaging (MRI) compared with arthroscopy. MATERIAL AND METHOD:
      One hundred twenty eight consecutive patients who underwent MRI of the knee using
      a 3-T magnet between April 2007 and Nov 2008 were included in this study. The
      inclusion criteria were the patients who had (i) subsequent knee arthroscopy,
      (ii) available medical records, and (iii) no history of meniscal surgery. Their
      MR images were retrospectively reviewed by two radiologists with consensus
      agreement. The diagnostic values for diagnosing meniscal tears were evaluated and
      compared to the arthroscopic results. RESULTS: Thirty-two patients (64 menisci)
      were included; 26 males and 6 females, mean age was 36.4 years (range 19-62). The
      mean interval between MRI and arthroscopy was 93 days. To diagnose tear of
      medial, lateral, and both menisci; the sensitivity was 100%, 90%, 100%; the
      specificity was 77%, 73%, 50%; the accuracy was 91%, 78%, 84%; the positive
      predictive value (PPV) was 86%, 60%, 81%; and the negative predictive value (NPV)
      was 100%, 94%, 100%, respectively. False positive MR findings were found
      predominantly at the posterior horn and at the peripheral third of the menisci.
      By dividing the patients into 2 groups according to the mean MRI-arthroscopy
      interval (< 93 and > 93 days): increased sensitivity and NPV of detecting lateral
      meniscal tear; increased specificity, accuracy, and PPV of both meniscal tear was
      observed in the longer duration group, but there was no statistical significance
      in the present study. CONCLUSION: The present results with 3-T MRI revealed high
      sensitivity and NP V comparable to the literature, thus supporting previous
      studies that if a meniscal tear is not seen on 3-T MRI, it is highly unlikely to
      be present. False positive MR findings found predominantly at the posterior horn
      and at the peripheral third of the menisci. The longer the MRI-arthroscopy
      interval yielded increased diagnosing values of meniscal tear but there is no
      statistical significance in the present study

PMID- 20043571
TI  - Preliminary study of suprascapular nerve block (SSNB) in hemiplegic shoulder
      pain.
AB  - OBJECTIVE: To study the effectiveness of suprascapular nerve block in hemiplegic
      shoulder pain for reducing pain and increasing range of motion, and compare them
      to treatments with therapeutic ultrasound. STUDY DESIGN: Randomized controlled
      trial study. SETTING: Thai Red Cross Rehabilitation Center. MATERIAL AND METHOD:
      Stroke patients with hemiplegic shoulder pain who met the inclusion criteria were
      included into the present study and allocated to the suprascapular nerve block
      (SSNB) and ultrasound groups by block of four-randomization technique. Patients
      of the SSNB group were done the nerve block twice, after pre-assessment on the
      first day and the next week of follow-up. For the ultrasound group, patients were
      treated 5 days a week. During four weeks of study, all of the patients were given
      the same standard program of range of motion exercise and were evaluated the VAS
      score of pain and range of motion every week until four weeks. RESULTS: Ten
      stroke patients were equally allocated to SSNB and US groups. There were
      significant improvements of VAS score at the 2nd and 4th week in the SSNB group
      with mean decreasing VAS scores of 40.6 +/- 25.4 and 51.0 +/- 20.7 respectively.
      For ROM outcome of the SSNB group, the increase offlexion at the 2nd and 4th week
      was 17.0 +/- 6.3 and 25.4 +/- 10.4 and abduction was 13.2 +/- 11.3 and 20.6 +/-
      12.5, respectively. Statistically significant increase was detected at the 4th
      week inflexion motion (p = 0.026). SSNB produced a faster relief of pain than the
      ultrasound but there was no significant difference for restoration of ROM There
      was no complication observed during the present study. CONCLUSION: The present
      study suggests that suprascapular nerve block is a safe and effective treatment
      for hemiplegic shoulder pain. It was more rapid and effective than therapeutic
      ultrasound in reducing pain score but there is a similar result for improvement
      of ROM.

PMID- 20043572
TI  - Drug metabolizing enzyme CYP1A2 status in pediatric patients with hemoglobin E
      beta thalassemia.
AB  - OBJECTIVE: To evaluate the drug metabolizing enzyme CYP1A2 activity in pediatric
      hemoglobin E-beta-thalassemia patients, since CYP1A2 is responsible for the
      metabolism of a number of drugs. Alteration of its activity may have clinical
      consequences. MATERIAL AND METHOD: Twenty-three hemoglobin E-beta thalassemia
      pediatric patients and 24 age-matched controls were recruited in the present
      study. Caffeine in the form of a soft drink was orally administered as a test
      probe for CYP1A2 activity. Plasma collected at pre-dose and 6 hr after intake was
      analyzed for the levels of caffeine and paraxanthine, its major metabolite to
      represent the activity of CYPIA2. RESULTS: Biochemical markers, including blood
      glutathione and urinary lipid hydroperoxides indicated that patients were in an
      oxidant stress state. The plasma ratio of paraxanthine to caffeine was unchanged
      between patients and controls. Multiple regression analysis revealed that gender
      and the liver enzyme were the significant determinants of CYP1A2 activity
      (adjusted r2 = 0.48, p < 0.001). Male gender was associated with higher activity
      of CYP1A2 activity. CONCLUSION: The CYP1A2 activity is not apparently changed in
      thalassemia patients despite the presence of an oxidative stress state.

PMID- 20043573
TI  - Quality of cold storage drugs transportation and delivery to Thai hospitals.
AB  - BACKGROUND: In Thailand there is no regulation and standard guideline to control
      the quality of drug transportation, including cold storage drugs. OBJECTIVE: To
      explore the condition of cold storage drugs transportation and delivery to
      general public hospitals, community hospitals and private hospitals. MATERIAL AND
      METHOD: This is a cross-sectional survey research. There were 301 questionnaires
      returned from 720 questionnaires sent (41.8% response rate) RESULTS: The serious
      problems of cold storage drugs on delivery were (1) Cold storage drugs (2 degrees
      C - 8 degrees C) were delivered to the hospitals without controlled temperature
      boxes, was found in private, public and community hospitals at the rate of 46.7%,
      48.3% and 72.9% respectively. (2) Cold storage drugs (-20 "C), i.e., polio
      vaccine came to the hospitals with a temperature higher than 8C or ice melting in
      the box, was found in private, public and community hospitals at the rate of
      22.9%, 12.7% and 35.0% respectively. CONCLUSION: There are differences in quality
      of cold storage drug transportation and delivery among types of hospitals. It is
      highly recommended that Thai FDA should develop a standard and implement the
      control system for logistics management of cold storage drugs.

PMID- 20043574
TI  - Female genital tract tumors and gastrointestinal lesions in the Peutz-Jeghers
      syndrome.
AB  - BACKGROUND: Peutz-Jeghers Syndrome (PJS) is a rare genetic disorder characterized
      by mucocutaneous melanin deposition, and intestinal hamartomatous polyps, with an
      increased risk of breast, gastrointestinal, and female genital tract cancers.
      CASE REPORT: Multiple genital tract neoplasms in a 52-year-old northern Thai
      woman with PJS are described. The patient presented with abdominal distention. A
      pelvic ultrasound scan showed a left adnexal mass, diagnosed as mucinous cyst. An
      ovarian microscopic cystadenoma was diagnosed together with a minimal deviation
      mucinous adenocarcinoma (MDA) of the uterine cervix and mucinous metaplasia in
      tubal mucosa and endometrium. Pathological findings warranted a search for
      evidence of PJS Typical pigmentation at the hard palate and colonoscopic finding
      of hamartomatous polyps established the diagnosis of PJS. At four-year follow-up,
      the patient still showed no evidence of tumor recurrence. CONCLUSION: A case of
      PJS complicated by multiple and contemporaneous genital tract tumors with rare
      histological findings is presented. The presented case suggests MDA and mucinous
      metaplasia warrant a search for PJS.

PMID- 20043575
TI  - Phrenic nerve stimulation for diaphragmatic pacing in a patient with high
      cervical spinal cord injury.
AB  - BACKGROUND: Phrenic nerve stimulation is a therapeutic option for patients with
      central hypoventilation syndrome due to brain stem and high cervical spinal cord
      dysfunction. CASE REPORT: A 28-year-old woman with high cervical spinal cord
      injury at the level of C2 had chronic central hypoventilation syndrome, requiring
      long-term use of a home ventilator Preoperative end tidal CO2 and tidal volume
      during spontaneous breathing indicated hypoventilation syndrome. Bilateral
      phrenic nerve stimulation for diaphragmatic pacing was performed with spinal cord
      stimulators used for chronic pain. The end tidal CO2 pressure (ETCO2), tidal
      volume, and spontaneous breathing time have improved up to 29 months of
      postoperative follow-up period. CONCLUSION: Phrenic nerve stimulation for
      diaphragmatic pacing can reduce all-time requirement of ventilatory support in
      patients with high cervical spinal cord injury.

PMID- 20043576
TI  - [Alterations of metalloproteinases and their inhibitors concentrations in
      peripheral blood in children with congenital heart disease undergoing cardiac
      surgery with cardiopulmonary bypass].
AB  - Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital
      heart disease induces neutrophil activation, degranulation and systemic
      inflammatory response. Matrix metalloproteinase-9 (MMP-9) and matrix
      metalloproteinase-2 (MMP-2) are enzymes involved in degranulation and leukocyte
      extravasation. These are secreted as a pro-enzyme in response to several
      inflammatory mediators and are inhibited by tissue inhibitor of metalloproteinase
      1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2). To explore
      metalloproteinase activation during cardiac surgery we investigated MMP-9, MMP-2,
      TIMP-1 and TIPM-2 levels in young children during and after surgery. We measured
      the dynamics of these enzyme concentrations in peripheral blood. Additionally we
      measured CD11b and CD66b molecule expression on neutrophils. These investigations
      were carried out in 39 children, aged 5-38 months who were undergoing
      cardiacsurgery with cardiopulmonary bypass (CPB). Serum concentrations of MMPs
      and their inhibitors, CD11b and CD66b expression on neutrophils were sequentially
      measured before induction of anesthesia, at the initiation of CPB, after 30
      minutes of CPB, at the end of CPB, 4 and 48 hours after CPB. MMP-9 concentration
      increased at the end of CPB and remained elevated for a period of 48 hours. The
      concentration of MMP-9 detected at the end of CPB positively correlated with time
      of CPB (r=0.68, p=0.0045). TIMP-1 concentration decreased significantly after 30
      minutes of CPB, remained lowered to the end of CPB, and returned to the start of
      CPB level after 48 hours. CD11b and CD66b expression on neutrophils increased at
      the initiation of CPB. Our data confirm that MMPs play an important role in
      inflammatory complications after cardiac surgery in children. These findings
      suggest that kinetics of MMPs concentrations in serum after cardiac surgery
      appear to depend on many factors. We demonstrated the link between CPB duration
      and the MMP-9 concentration. Future studies will determine whether inhibition of
      MMPs activity diminishes morbidity in children after cardiac surgery.

PMID- 20043577
TI  - [The plasma levels and diagnostic utility of granulocyte-colony stimulating
      factor (G-CSF) and granulocyte-macrophage - colony stimulating factor (GM-CSF) in
      patients with I and II stage of breast cancer].
AB  - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) and granulocyte
      macrophage - colony stimulating factor (GM-CSF) belong to hematopoetic growth
      factors (HGFs). Few clinical investigation have shown their autologous production
      both in vitro by human cell lines and in vivo by tumors, for example in breast
      cancer. We have investigated the plasma levels of G-CSF, GM-CSF and commonly
      accepted tumor marker (CA 15-3) before treatment of breast cancer patients in
      relation to the healthy controls. Additionally, the diagnostic criteria:
      sensitivity, specificity, the predictive value of positive and negative results
      were defined. MATERIAL AND METHODS: Tested group--50 patients with breast cancer,
      control group--30 healthy women. G-CSF and GM-CSF were determined using ELISA
      method, CA 15-3--was measured by chemilumunescence immunoassay (CMIA) (ABBOTT).
      RESULTS: Median values of G-CSF, GM-CSF and CA 15-3 plasma levels were
      significantly higher in the II stage of breast cancer patients before surgery
      compared to the control group. The diagnostic sensitivity of G-CSF and GM-CSF was
      slightly lower than CA 15-3. The higher range of the diagnostic sensitivity of
      tested cytokines and CA 15-3 in more advanced breast stages was observed. The
      combined use of both cytokines and CA 15-3 analysis resulted also in the
      increased sensitivity range (69%). The diagnostic specificities of tested
      cytokines were high for both cytokines (equal 90%) and CA 15-3 (95%). The
      positive and negative predictive values were high for all tested parameters and
      were higher in more advanced tumor stage. CONCLUSIONS: This study suggests that
      tested cytokines, especially G-CSF, can be clinically useful in diagnostics of
      breast cancer patients, but further investigation and confirmation by a
      prospective study are necessary.

PMID- 20043578
TI  - [Coeliac disease and other autoimmunological disorders coexistance].
AB  - Coeliac disease (gluten enteropathy) is a chronic inflammatory disease of the
      gastrointestinal (GI) tract of autoimmune etiology in genetically predisposed
      individuals. It is the most frequent enteropathy with frequency of 1/100 and
      1/300 in the adult population in America and Europe respectively. Typical form of
      celiac disease including abdominal pain, weight loss, nausea is quite rare in
      adults. In some coeliac patients, symptoms persist in spite of strict gluten free
      diet. One of the reasons of this is interference of the autoimmune diseases.
      Results of our studies revealed in the group of 110 patients with diagnosed
      gluten enteropathy, coexistence of autoimmune disease, such as diabetes mellitus
      type 1 in 7.2% cases, hyperthyreosis on 1.8% of cases, vitiligo in 0.9% of cases,
      primary biliary cirrhosis in 2% of cases and rheumatoidal arthritis in 0,9 of
      cases. In the group of 80 ulcerative colitis patients, coexistence of celiac
      disease basing on serological histopatological investigation was found in 4
      patients (5%). CONCLUSIONS: Coexistence of coeliac disease with other autoimmune
      diseases is quite frequent. Gluten enteropathy symptoms may be interpreted as
      originating from other autoimmune disease. It can delay the diagnosis of celiac
      disease and introduction of gluten free diet, which improves the quality of life
      and protects from dangerous GI complications.

PMID- 20043579
TI  - [Bacteriological spectrum of periodontal pocket in patients with coronary heart
      disease and myocardial infarction].
AB  - INTRODUCTION: In the last years literature has paid attention to positive
      correlation between periodontitis and coronary heart disease, acute coronary
      events, including myocardial infarction. Mechanisms of this relationship are not
      completely known. One of the research trends for elucidation of these problems
      are bacteriological studies. The aim of this study was qualitative and
      quantitative evaluation of bacterial flora of the periodontal pocket in patients
      with coronary heart disease and myocardial infarction, with co-existing
      periodontitis. MATERIAL AND METHODS: The research included 40 patients,
      hospitalised in 1st Clinic of Cardiology, Medical University in Gdansk. Group 1
      included 20 patients after myocardial infarction, group 2 of 20 patients with
      diagnosed coronary heart disease, with many years duration without acute events.
      Control group encompassed 20 patients of Chair and Department of Periodontology
      and Oral Mucosa Diseases, Medical University in Gdansk, without cardiovascular
      diseases. Inclusion criterion for the study was diagnosed chronic periodontitis
      in all patients. In clinical evaluation indices: API, SBI, PD and CAL were used.
      The material for bacteriological research was taken in each patient from 4
      periodontal pockets, minimum 5 mm depth. The culture and identification were
      performed with present principles. Based on the litearture data about potential
      pathogenicity for periodontium and cardiovascular system, species for analyse
      were chosen. RESULTS: Statistical analyse proved equality of evaluated groups and
      control group in gender, age and estimated clinical indices. In periodontal
      pockets all patients anaerobic flora dominated, however without significiant
      differences in species range. Among microaerophilia and streptococci statistical
      analyse showed significiant differences in frequency of isolation of
      Actinobacillus actinomycetescomitans and Streptococcus sanguis in group 1 in
      comparision to group 2 and control group. Quantitative analyse showed no
      significiant differences between groups for all bacteria species. CONCLUSIONS:
      Clinical evaluation showed comparable values of periodontal parameters. The
      bacteria species Porphyromonas gingivalis, Actinobacillus actinomycetescomitans
      and Streptococcus sanguis were more often isolated from periodontal pockets in
      persons after myocardial infarction, statistically significant for A.a. and S.s.

PMID- 20043580
TI  - [Postinfarction cardiac remodeling--clinical consequences].
AB  - Despite the considerable progress in the setting of invasive and pharmacological
      treatment still in about 20-30% patients with myocardial infarction in long-term
      observation an unfavourable post-infarction remodeling along with development of
      LV dilatation is to be seen. The heart forms the structural and functional unity,
      thus morphological changes due to cardiac post-infarction remodeling process are
      accompanied by systolic and diastolic myocardial dysfunction, which in
      consequence may lead to appearance of heart failure. In recent years our
      knowledge regarding causative factors of post-infarction cardiac remodeling has
      been remarkably widening and in the light of accumulating data indicating the
      possibility of LV remodeling regression, elaboration of the new specific
      orientated methods of counteracting its uneventful consequenses is a matter of
      time.

PMID- 20043581
TI  - [Physical training as immunomodulatory treatment in chronic heart failure].
AB  - Exercise training is an established method of treatment in patients with chronic
      heart failure (CHF), which is still underused in Poland. It has been shown to
      improve exercise tolerance, physical fitness, clinical status and probably
      prognosis. Mechanism of it's beneficial effects is under investigation, to answer
      the question, whether exercise training just reverses changes caused by decrease
      in physical activity or interferes with the catabolic factors involved in the
      pathogenesis of myopathy. According to "cytokine theory", progression of CHF is
      at least partly due to the inflammatory process with cytokines in it's center. In
      this context it is investigated whether exercise training has immunomodulatory
      effects. This paper reviews the role of inflammation in the pathogenesis of CHF.
      It is stressed that intensive exercise increases inflammation. In this context
      immunomodulatory effects of exercise training are discussed. Papers review
      effects of physical training, taken into consideration different forms of
      training, it's influence of different stages of inflammation and clinical status
      of patients. It is emphasized, that probably there are differences in training
      effects in relation to etiology of CHF. There are not many studies concerning
      these problems. It seems, based on their results that improvement of exercise
      capacity and clinical status after exercise training may be, at least partly,
      explained by decrease in inflammatory reaction. These papers contributes to
      better understanding of the role of inflammation in CHF and open a new scope of
      investigation asking new questions.

PMID- 20043582
TI  - [Could oral antidiabetic agents be useful in the management of different types of
      diabetes and syndromes of insulin resistance in children and adolescents?].
AB  - Various pharmacological approaches can be used to improve glucose homeostasis.
      These pharmacological treatments may be used individually for certain types of
      patients, or may be combined to provide a more ideal glycaemic control. Metformin
      is widely used in pediatric patients and is considered to be the most effective
      oral agent. Addition of metformin to insulin in pediatric patients with type 1
      diabetes mellitus improves metabolic control. Metformin acts by promoting glucose
      utilization and reducing hepatic glucose production. In many patients with type 2
      diabetes, hyperglycemia can be reduced with appropriate changes in diet and
      exercise, however, some patients with type 2 diabetes and insulin resistance
      syndromes need pharmacological therapy to improve their metabolic control. The
      first oral agent used should be metformin. More severe pancreatic beta-cell
      dysfunction in the group of children requires insulin therapy. Some forms of
      monogenic diabetes can be successfully managed by sulphonylurea agents.

PMID- 20043583
TI  - [Feto-placental blood flow--practical remarks].
AB  - Pregnancy is a physiological state which still needs close observation from the
      very beginning till the delivery to decrease the potential risk of complications
      for the mother and her baby. The finding of pathology is possible thanks to
      advanced diagnostic technology--cardiotocograph and ultrasonography, especially
      Doppler technique. Monitoring of the fetus is based not only on the routine
      obstetric examination, but also on the observation and analysis of the fetal
      heart rate, biometry measurements with expected fetus weight, as well as
      assessment of blood flow in the fetal, the umbilical and uterine vessels.
      Assuming that pathology in fetal heart rate can predict intrauterine discomfort,
      early examination and appropriate reaction to the situation is essential. Early
      identification of intrauterine growth restriction enables intensive treatment
      which improves the outcome and reduces perinatal mortality. Information
      concerning biophysical monitoring of a fetus and basic rules of test result
      interpretations of are presented in this article.

PMID- 20043584
TI  - [Influence of anticoagulants on the appearance of chronic subdural hematoma].
AB  - In recent years in the Department of Neurotraumatology in Cracow it has been
      noticed the frequent connection between appearance of chronic subdural hematoma
      (CSDH) and treatment by anticoagulant medications. The aim of this study is to
      draw attention to the problem of insufficient control of anticoagulants
      consumption, especially by patients treated for cardiovascular system diseases
      that increases the risk of bleeding and CSDH development. The paper is based on
      data from questionnaires that was sent to patients with CSDH, cured in the
      Department of Neurotraumatology form 2004 to 2005. Analyzed was the group of 51
      patients with chronic subdural hematoma; 37 individuals (72.5%) confirmed taking
      acetylsalicylic acid in the period of 3 months before admission to the
      Department, 9 (17.6%) patients answered that they were taking low-molecular
      weight heparin. One patient (1.9%) was taking chronically derivative of cumarin.
      The authors would inform that anticoagulant treatment might favour increase of
      chronic subdural hematoma incidence. It's especially important, because the
      average life expectancy has been prolonged in Poland and there are more people
      taking acetylsalicylic acid. This can be an epidemiological problem in future.

PMID- 20043585
TI  - [Case report of live threatening complications due to self insertion of foreign
      body into the vagina for masturbation purpose].
AB  - Authors have reported a case report of life threatening complications due to
      insertion of foreign bodies into the vagina, because of masturbation purpose. In
      this case subsequently came to perforation of the urinary bladder by the huge
      calculus that developed over the foreign body, and next to the peritoneum with
      development peritonitis and acute renal insufficiency with the need of
      dialysotherapy. After a number of surgical operations, the patient with a
      definitive percutaneous nephrostomy was discharged.

PMID- 20043586
TI  - [Venous thrombosis as a barrier in cardiac resynchronization therapy--case
      report].
AB  - According to results of several international clinical trials, Cardiac
      Resynchronisation Therapy (CRT) among patients with moderately or severely
      damaged heart's pumping capacity improves quality of life along with reduction of
      combined morbidity and hospitalisation measures. The procedure involves placing
      leads in both ventricles and as all complicated heart catheter procedures can be
      disturbed in many ways. In order to present possible difficulties occurring
      during the procedure, we investigate one case of ineffective CRT device
      implantation. We report a patient with permanent ventricular pacing treated in
      the Department of Electrocardiology, John Paul II Hospital in Krakow, who was
      admitted with signs of circulatory decompensation and consequently qualified for
      CRT. Although the patient was remaining in permanently controlled coumarine
      therapy, the massive thrombosis made the CRT impossible. In this rare condition
      following procedures are under consideration: implanting the electrode from the
      left side and connecting it to the right side located pacemaker (unless there is
      no thrombosis on this side), microthoracotomy with Hunter electrode epicardial
      placement to restore the proper heart stimulation. This case report highlights
      the importance of considering potential difficulties occurring during various
      electrocardiological procedures in patients with impaired pacemaker function.

PMID- 20043587
TI  - Gastric emptying in patients with gastroesophageal reflux disease and
      postprandial distress syndrome--preliminary results.
AB  - BACKGROUND: Gastric motor disturbances are observed in patients with both
      Gastroesophageal Reflux Disease (GERD) forms - with (ERD) and without (NERD)
      esophageal inflammatory changes, and in Functional Dyspepsia (FD) patients,
      particularly in those with Postprandial Distress Syndrome (PDS). Gastric
      Helicobacter pylori (Hp) infection is often present in these entities. We tried
      to evaluate if there is any influence of Hp on gastric emptying (GE) in reflux
      and dyspeptic patients. MATERIAL AND METHODS: 25 GERD patients aged 45.7+/-13.1
      yrs (10 NERD; 5 Hp+ and 5 Hp- and 15 ERD with grade A esophagitis according to
      Los Angeles classification; 5 Hp+ and 10 Hp-) and 15 PDS patients (5 Hp+ and 10
      Hp-) aged 47.9+/-14.0 yrs participated in our study. All patients underwent upper
      gastrointestinal tract endoscopy, Hp status verification, stationary esopageal
      manometry, 24-hour ambulatory pH-metry and gastric scintigraphy with a liquid
      test meal. RESULTS: In general, both GERD groups and PDS patients had prolonged
      GE (T1/2 - NERD-54.9 +/- 6.3 [min], ERD-41.7 +/- 14.8 [min] and PDS-54.3 +/- 24.8
      [min] vs. 35.2 +/- 13.9 [min] in control; p<0,05). According to Hp infection, we
      found in both NERD and PDS groups prolonged GE in Hp+ subjects in comparison to
      Hp-ones (respectively: T 1/2 - 66.5 +/- 21.2 [min] vs. 43.8 +/- 11.4 [min] in
      NERD; p<0.05; 63.5 +/- 29.0 [min] vs. 48.0 +/- 27.7 [min] in PDS; p<0.05). These
      differences were less pronounced in ERD subjects: 44.5 +/- 17.7 [min] Hp+ vs.
      37.4 +/- 15.2 [min] in Hp- ERD; p>0.05). CONCLUSIONS: Both NERD and PDS patients
      had more decreased GE half-time compared to those with inflammatory esophageal
      changes. In particular groups, Hp infection was associated with slower GE rate
      and elongated T 1/2 in NERD and PDS group but with no effect in ERD patients.

PMID- 20043588
TI  - [Radiofrequency catheter ablation in the treatment of arrhythmias in children-
      efficacy, safety of the method, predictors of the procedural course and acute
      success].
AB  - BACKGROUND: Radiofrequency current ablation (RFCA) is a safe and efficient method
      of treatment in adult patients with symptomatic arrhythmias. Recently RFCA is
      being also used in the treatment of children with cardiac arrhythmias, however
      its value in this set of patients is poorly documented. Aims of our study were to
      assess the feasibility and safety of RFCA procedures in children with symptomatic
      supraventricular and ventricular arrhythmias, and to identify the parameters
      which influence the probability of acute success and RFCA course. METHODS:
      Consecutive 110 patients aged less than 18, who underwent RFCA due to the
      symptomatic arrhythmias at our center were included into a retrospective
      analysis. The patients presented mainly with the preexcitation syndrome (57%),
      13.6% had ectopic ventricular arrhythmias, in 17.3% nodal reentrant tachycardia,
      in 8.2% intraatrial reentry tachycardia (IART), whereas in 5.4% ectopic atrial
      tachycardia (EAT) was diagnosed. Three patients had multiple arrhythmias. In ten
      subjects congenital heart defect was diagnosed in the past, which was treated
      surgically in 8. Analyzed parameters included: RFCA success-rate, procedure
      duration, fluoroscopy-time, perioperative complications and arrhythmia recurrence
      rate during 6 months follow-up. RESULTS: Ablation was successful in 101 (91.8%)
      patients and abolished 104 out of 113 (92%) treated arrhythmias. Out of 9
      patients with unsuccessful RFCA, three had congenital heart defect. Two
      complications occurred intra-operatively in two patients: in one patient
      pneumothorax was observed following jugular vein puncture, which resolved
      spontaneously without the need of drainage, in the second patient transient
      atrioventricular conduction block occurred during radiofrequency current
      application. Mean procedure duration in the studied population was 118.9 +/- 46
      min, fluoroscopy exposure equaled 22.3 +/- 17min. In twelve patients (10.9%)
      arrhythmia recurred during the follow-up period. The longest procedure duration
      was observed in patients with EAT and IART, the longest fluoroscopy-time in
      subjects with IART, whereas the shortest fluoroscopy was observed in patients
      with the ventricular ectopic arrhythmias. Success-rates, complications, and
      recurrence-rates did not differ irrespectively from arrhythmia treated. The only
      independent predictor of unsuccessful RFCA was the presence of congenital cardiac
      defect (adjusted OR 0.15, p<0.05). The presence of cardiac defect, procedure
      performed without electroanatomic mapping system and less experienced operators
      were the parameters associated with longer fluoroscopic exposure. CONCLUSIONS:
      Radiofrequency current ablation is a safe and efficient method of treatment in
      children with arrhythmias. The presence of congenital heart defect was a factor
      influencing unfavorably the probability of successful RFCA. Procedural course was
      related to the experience of electrophysiology team, the use of advanced mapping
      systems and presence of cardiac defect.

PMID- 20043589
TI  - [Prognostic value of laboratory factors of performance status in lung cancer
      patients].
AB  - Clinical observations indicate that the utility of classical prognostic factors
      in the assessment of probability of disease free or overall survival of lung
      cancer patients is not completely satisfactory. This is the cause for search of
      indices which results would contribute to optimization of this estimation. Of
      potential value in this aspect may also be the results of laboratory
      determinations which characterize patient's performance status. Dependencies
      between the times of overall survival in respect to chosen hematological and
      biochemical factors from the pretreatment period were analyzed in a group of 233
      patients with lung cancer (adenocarcinoma - 44, squamous cell lung cancer - 156,
      small cell lung cancer - 33 patients) in different stages of disease. Apart from
      stage of disease and histological type of tumor, independent prognostic factors
      turned out to be the actual ideal body mass ratio and the number of leucocytes.
      In patients with less advanced stages of disease, such independent factors, apart
      from histological type are alpha-1 globulin and gamma globulin.

PMID- 20043590
TI  - [The plasma level of sL-selectin, myeloperoxidase (MPO) and granulocyte-colony
      stimulating factor (G-CSF) in breast cancer patients after surgery].
AB  - G-CSF is a stimulatory factor of granulocyte colony formation. In vitro and in
      vivo G-CSF enhances functions of mature cells. Indirect evidence of this might be
      the increase of the activity of granulocyte enzymes participating in phagocytosis
      and killing tumor cells. The purpose of this investigation was to evaluate in the
      plasma of breast cancer patients the level of adhesion molecule - sL-selection,
      as a measure of mature granulocyte activity and MPO, granulocyte enzyme
      responsible for the cytotoxicity. Additionally we have investigated the plasma
      level of G-CSF which can increase in breast cancer. We tested 16 patients with I
      stage breast cancer and 15 patients with II stage breast cancer. Plasma samples
      were drawn before and 30 days after operation. The control group consisted of 10
      healthy women. The plasma levels of sL-selectin, MPO and G-CSF were measured
      using breast cancer patients (I and II stage) before and after operation of sL
      selection concentration was increased in comparison to the control group, but
      myeloperoxidase concentration was similar to the control group. These results
      suggest that levels of sL-selectin and MPO correlate with G-CSF concentration.

PMID- 20043591
TI  - [Application of computer aided diagnosis (CAD) in clinical imaging. Presentation
      of the value and current directions in CAD development in various imaging
      techniques based on literature review].
AB  - Computer aided diagnosis (CAD) is a currently applied computerized analysis of
      medical images and is widely used as a tool in detection and differential
      diagnosis of abnormalities in medical imaging. In clinical practice CAD became a
      very useful implement in various imaging techniques such as mammography,
      radiography, CT, MRI or diagnostic ultrasound. CAD became also a major research
      subject in clinical radiology e.g. in detection of pulmonary nodules in chest CT
      or breast cancer on mammograms. CAD concept, unlike known from 1960s automated
      computer diagnosis concept (ACD), which is based on computer algorithms only
      takes into account equally the roles of physician and computer. Current
      directions in CAD development focus on continuous improvement of overall
      performance in detection of pathological lesions and assembling CAD schemes as
      packages implemented as a part of PACS system. The aim of this article is
      presentation of the concept of computer aided diagnosis, current opportunities of
      adopting CAD systems into various imaging techniques and new directions in CAD
      development.

PMID- 20043592
TI  - [Homocysteine and asymmetric dimethylarginine (ADMA) in epilepsy].
AB  - Homocysteine (Hcy) is a thyol amino acid resulting from demethylation of
      methionine. It is metabolized through two pathways: remethylation and
      trassulfuration, which use as cofactors folate, vitamin B6 and vitamin B12.
      Hyperhomocysteinemia (hHcy) is a risk factor for cerebrovascular disease,
      dementia, inborn defects, impaired cognitive function. Several drugs may change
      metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. HHcy
      has been documented in epileptic patients after chronic treatment with
      antiepileptic drugs (carbamazepine, valproate). HHcy may lead to increase of the
      level of asymmetric dimethylarginine (ADMA). ADMA has been identified as a
      potential risk factor for cardiovascular disease and endothelial dysfunction.
      ADMA is a product of methylation of L-arginine and endogenous nitric oxide (NO)
      synthase inhibitor, and regulator of NO production. NO plays a role in the
      convulsant effect. Supplementation of B vitamins, folate and L-arginine is a
      strategy to reduce Hcy levels in patients with epilepsy treatment antiepileptic
      drugs.

PMID- 20043593
TI  - [Characteristic of adverse reactions after blood components transfusion].
AB  - The adverse transfusion reaction is usually defined as an unwanted reaction
      occurring in a recipient during or after a blood transfusion or its components.
      Adverse reaction can occur even in 10% of recipients. The after transfusion
      reactions can be divided with regard to its causes: infectious and non
      infectious, of immunologic and non-immunologic. Blood component transfusions can
      be related to unfavorable transfusion reaction of early or delayed character.

PMID- 20043595
TI  - [Poisoning with weever fish venom: a case report].
AB  - Poland's access to the EU causes that there is the risk of poisoning from sources
      outside Poland. This is confirmed by the case reported below. The Weeverfish
      Trachinus draco lives in the coastal waters of West Africa and Europe (including
      those of the Mediterranean Sea) and belongs to the most poisonous fish species.
      The venom of Trachinus draco contains proteins that cause cellular membrane
      depolarisation, and haemolysis. A 35-yr. man was admitted to the Toxicological
      Department of the Nofer Institute of Occupational Medicine for symptoms, such as:
      a strong pain, swelling and reddening of the left leg, that had appeared after
      contact with an unidentified fish when he had been enjoying a bath in the
      Mediterranean Sea. In the additional examinations, slight abnormalities were
      detected only in the results of blood agglutination test. The patient was
      discharged from the hospital 7 days later in good condition.

PMID- 20043594
TI  - [IgA multiple myeloma with adverse prognostic factors--a case report].
AB  - IgA multiple myeloma is the second most frequent variant of multiple myeloma. The
      median survival is about 3 years and depends on presence, or not, certain
      prognostic factors. Cytogenetic status has become the most important of them. The
      presence of the chromosome 13 deletion is an independent adverse prognostic
      marker in multiple myeloma and is associated with specific biological features.
      Patients with the chromosome 13 alterations are less likely to respond to
      treatment and have a shorter median overall survival. We present a case of IgA
      multiple myeloma, which was even resistant to new therapeutic strategies
      (thalidomide, bortezomib).

PMID- 20043596
TI  - [Celiac disease and other immunomediated diseases coexistance and influence of
      clinical course. Case report].
AB  - Celiac disease (gluten enteropathy) is chronic immunomediated disorder of
      gastrointestinal tract in genetically predisposed patients. We present the case
      of 46 years old man, with already diagnosed several autoimmune disorders, such
      as: diabetes mellitus LADA type, Graves-Basedow disease and vitiligo. Despite
      treatment of the above diseases, diarrhea and persistent abdominal pain was
      observed. Diagnosis of gluten enteropathy based on serology and histological
      evaluation of biopsies from distal part of duodenum enabled us to introduce
      gluten free diet, which contributed to attenuation of symptoms and better control
      of glucose serum levels. We think, that celiac disease should be taken into the
      consideration in differential diagnosis of chronic diarrhea and persistent
      abdominal pain, especially in patients with coexisting autoimmune diseases.

PMID- 20043597
TI  - [Nurses and doctors--prognosis for the future].
AB  - Mutual cooperation between medical doctor and nurses are presented, while
      analizing new trends in the European Union. Nurse family practice and specialist
      training are discussed as well as new specializations, i.e. Study nurse trained
      for participation in clinical trials.

PMID- 20043598
TI  - Trachoma surveillance annual report, 2008. A report by the National Trachoma
      Surveillance and Reporting Unit.
AB  - The National Trachoma Surveillance and Reporting Unit has reported data for
      trachoma endemic regions and communities in the Northern Territory, South
      Australia and Western Australia for 2006 to 2008. Aboriginal children aged 1-9
      years were examined using the World Health Organization grading criteria.
      Screening in the Northern Territory was conducted by the primary health care
      staff from the Healthy School Age Kids program, the Australian Government
      Emergency Intervention and Aboriginal Community Controlled Health Services. Forty
      three of 92 communities in 6 regions were screened and reported data (2,462
      children). In South Australia, the Eye Health and Chronic Disease Specialist
      Support Program and a team of eye specialists visited 11 of 72 communities in
      regions serviced by 6 Aboriginal Community Controlled Health Services (365
      children). In Western Australia, population health unit and primary health care
      staff screened and reported data for 67 of 123 communities in 4 regions (1,823
      children). Prevalence rates of active trachoma varied between the regions with
      reported prevalence ranging from 4%-67% in the Northern Territory, 0%-13% in
      South Australia and 8%-25% in Western Australia. Statistical comparisons must be
      viewed with caution due to the year-to-year variation in the coverage of children
      examined and the small numbers. Comparisons of 2006, 2007 and 2008 regional
      prevalence of active trachoma showed that many communities had no change in
      prevalence, though there were a few statistically significant increases and
      decreases (P<0.05). The number of communities screened and the number of children
      examined has improved but still remains low for some regions. The implementation
      of the World Health Organization Surgery (for trichiasis), Antibiotics (with
      azithromycin), Facial cleanliness and Environmental improvement (SAFE) strategy
      has been variable. Few data continue to be reported for the surgery and
      environmental improvement components. In general, the availability of the
      community programs for surgery, antibiotic treatment, and facial cleanliness has
      improved. Reporting of antibiotic treatment has improved from 2006 to 2008. No
      significant changes were noted in bacterial resistance reported by pathology
      services from 2007 to 2008; these rates are comparable to national data collected
      by the Advisory Group on Antibiotic Resistance in 2005.

PMID- 20043599
TI  - Annual report of the Australian National Poliovirus Reference Laboratory, 2008.
AB  - The Australian National Poliovirus Reference Laboratory (NPRL) is accredited by
      the World Health Organization (WHO) for the testing of stool specimens from cases
      of acute flaccid paralysis (AFP), a major clinical presentation of poliovirus
      infection. The NPRL, in collaboration with the Australian Paediatric Surveillance
      Unit, co-ordinates surveillance for cases of AFP in children in Australia,
      according to criteria recommended by the WHO. Clinical specimens are referred
      from AFP cases in children and suspected case of poliomyelitis in persons of any
      age. The WHO AFP surveillance performance indicator for a polio-free country such
      as Australia, is 1 non-polio AFP case per 100,000 children less than 15 years of
      age. In 2008, the Polio Expert Committee (PEC) classified 62 cases as non-polio
      AFP, or 1.51 non-polio AFP cases per 100,000 children aged less than 15 years.
      Poliovirus infection is confirmed by virus culture of stool specimens from AFP
      cases as other conditions that present with acute paralysis can mimic polio.
      While no poliovirus was reported in Australia from any source in 2008, the non
      polio enteroviruses echovirus 25, coxsackievirus B2 and echovirus 11 were
      isolated from stool specimens of AFP cases. The last report of a wild poliovirus
      in Australia was due to an importation from Pakistan in 2007. With 4 countries
      remaining endemic for poliomyelitis--Afghanistan, India, Nigeria and Pakistan-
      and more than 1,600 confirmed cases of wild poliovirus infection in 18 countries
      in 2008, Australia continues to be at risk of further importation events.

PMID- 20043600
TI  - Tuberculosis in Australia: bacteriologically confirmed cases and drug resistance,
      2007. A report of the Australian Mycobacterium Reference Laboratory Network.
AB  - The Australian Mycobacterium Reference Laboratory Network collects and analyses
      laboratory data on new cases of disease caused by the Mycobacterium tuberculosis
      complex. In 2007, a total of 872 cases were identified by bacteriology; an annual
      reporting rate of 4.1 cases per 100,000 population. Isolates were identified as
      M. tuberculosis (n=867), M. africanum (n=4) and M. bovis (n=1). Fifteen children
      aged under 10 years had bacteriologically-confirmed tuberculosis. Results of in
      vitro drug susceptibility testing were available for 871 of 872 isolates for
      isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z). A total of
      98 (11.3%) isolates of M. tuberculosis were resistant to at least one of these
      anti-tuberculosis agents. Resistance to at least H and R (defined as multi-drug
      resistance, MDR) was detected in 24 (2.8%) isolates, all from overseas-born
      patients; 17 were from the respiratory tract (sputum n=16, endotracheal aspirate
      n=1). Thirteen patients with MDR-TB were from the Papua New Guinea-Torres Strait
      Islands zone. Of the 98 M. tuberculosis isolates resistant to at least one of the
      standard drugs, 54 (55.1%) were from new cases, 9 (9.2%) from previously treated
      cases, and no information was available on the remaining 35 cases. Seven were
      Australian-born, 90 were overseas- born, and the country of birth of 1 was
      unknown. Of the 90 overseas-born persons with drug resistant disease, 66 (73.3%)
      were from 5 countries: India (n=16); Papua New Guinea (n=15); the Philippines
      (n=12); Vietnam (n=12); and China (n=11). No XDR-TB was detected in 2007.

PMID- 20043601
TI  - Tuberculosis notifications in Australia, 2007.
AB  - The National Notifiable Diseases Surveillance System received 1,135 tuberculosis
      (TB) notifications in 2007, of which 1,086 were new cases and 48 were relapsed
      cases. The incidence of TB in Australia in 2007 was 5.4 cases per 100,000
      population, similar to rates since 1986. In 2007, 86.4% of cases occurred in the
      overseas-born population. The incidence in the Indigenous Australian population
      was 6.6 cases per 100,000 population. By contrast, the incidence of TB in the non
      Indigenous population was 0.9 cases per 100,000 population. Household or other
      close contact with TB or past residence in a high risk country were the most
      commonly reported risk factors for TB infection. In 2007, 31 cases of TB were
      reported in health care workers, 29 of which were in health care workers born
      overseas. There were no reports of TB transmission in Australian health care
      settings. Outcome data of the 2006 TB cohort indicate that treatment success was
      attained in more than 95% of cases. As Australia continues to contribute to
      global TB control it is important to maintain good centralised reporting of TB to
      identify populations at risk and for early detection of reversal in trends in TB.

PMID- 20043602
TI  - Flutracking: a weekly Australian community online survey of influenza-like
      illness in 2006, 2007 and 2008.
AB  - Surveillance for influenza is an important public health function as it allows
      initiation and evaluation of public health measures. Flutracking is a weekly
      online survey of influenza-like illness (ILI) completed by community members that
      has been trialled in the 2006, 2007, and 2008 winter influenza seasons. The
      online survey allows participants to record their past and current influenza
      immunisation status and they receive a weekly email prompt to answer questions on
      the previous week's experience of cough, fever and time absent from normal
      activities. The weekly survey takes participants less than 15 seconds to
      complete. Symptom rates of Flutracking participants were compared by influenza
      vaccination status to estimate the incidence and severity of influenza and the
      field effectiveness of influenza vaccine. Participation rates increased from 394
      in 2006 to 982 in 2007 and 4,827 in 2008. In 2008, 56% of participants were from
      New South Wales and 26% were from Tasmania. Greater than 70% of respondents
      replied within 24 hours of the survey being sent in 2007 and 2008. The 2008
      influenza season appeared milder than 2007 with the peak weekly rate of cough and
      fever among all unvaccinated participants at 7% in 2008 compared with 15% in
      2007. The peak week of influenza activity detected by Flutracking in 2008 was the
      week ending 31 August, which was contemporaneous with the peak week in other
      syndromic and laboratory influenza surveillance systems. Participation in the
      survey continues to grow and appears sustainable. A more balanced recruitment
      across jurisdictions will provide a more national perspective.

PMID- 20043603
TI  - Flutracking surveillance: comparing 2007 New South Wales results with laboratory
      confirmed influenza notifications.
AB  - General practice and hospital surveillance for influenza-like illness (ILI) and
      laboratory influenza surveillance provide useful but incomplete information on
      influenza incidence. Flutracking is an Australian pilot of an Internet-based
      community ILI syndromic surveillance system designed to detect inter-pandemic
      and, potentially, pandemic influenza. Presence of fever and/or cough and absence
      from normal duties are collected weekly. Influenza vaccination status of
      respondents is recorded. New South Wales Flutracking data for 2007 were compared
      with New South Wales laboratory notifications for confirmed influenza to validate
      it's ability to provide alerts of influenza activity. Symptom rates amongst
      vaccinated and unvaccinated Flutracking respondents were compared using a variety
      of case definitions, with New South Wales laboratory influenza notifications.
      Time series methods were used to estimate the degree of correlation between each
      Flutracking case definition and the laboratory data. For the unvaccinated group,
      the correlations between all Flutracking case definitions and laboratory data
      were statistically significant, while for the vaccinated group no case
      definitions were significantly correlated with laboratory data. Thus Flutracking
      ILI data amongst unvaccinated participants correlated well with influenza
      laboratory surveillance.

PMID- 20043604
TI  - High proportion of influenza B characterises the 2008 influenza season in
      Victoria.
AB  - The 2008 influenza season in Victoria was distinctive because of the increased
      proportion of influenza-like illness (ILI) cases due to influenza B infection and
      the lateness of the season compared with preceding years. Influenza activity fell
      within the bounds of normal seasonal activity thresholds. The average rate of ILI
      reported by general practitioners participating in sentinel surveillance was 5.5
      cases per 1,000 consultations, peaking at 13.4 cases per 1,000 consultations. The
      average ILI rate reported by the Melbourne Medical Deputising Service was 5.1
      cases per 1,000 consultations over the season peaking at 16.2 cases per 1,000
      consultations at the same time as peak rates were reported by rural geneal
      practitioners (GPs), with a secondary peak observed 2 weeks later (10.9 cases per
      1,000 consultations). Metro GP rates peaked in week 35 (week beginning 25 August)
      at 15.2 cases per 1,000 consultations. Influenza B cases notified directly to the
      Victorian Department of Human Services (DHS) from other sources peaked in the 1st
      week of September with peak numbers of influenza A notifications occurring the
      following week. Overall 56% of notifications of laboratory confirmed influenza to
      DHS and 56% of influenza positive swabs from sentinel surveillance were influenza
      type B.

PMID- 20043606
TI  - Communicable diseases surveillance.

PMID- 20043605
TI  - Rotavirus vaccination one year on...
AB  - The rotavirus vaccine was incorporated into the Australian National Immunisation
      Program from 1 July 2007. To measure early impact of the vaccine on rotavirus
      disease and the burden of gastroenteritis in young children, we examined 2
      surveillance data sources, rotavirus isolates from selected New South Wales
      laboratories, and New South Wales Emergency Department (ED) visits assigned a
      gastroenteritis-related diagnosis. Between 2001 and 2008, weekly time series were
      prepared for 2 age groups representing children young enough to have been offered
      vaccination prior to the 2008 seasonal epidemic (< 15 months) and older children
      (15 months to 5 years). In 2008, the seasonal increase in laboratory confirmed
      rotavirus infection and gastroenteritis related ED visits declined substantially
      in both age groups compared with earlier years. These data provide preliminary
      evidence of the effectiveness of the rotavirus vaccination program in New South
      Wales. Immunising the most susceptible population group, infants, against
      rotavirus may limit wider circulation of the virus in older children.

PMID- 20043607
TI  - Health reform and the legislative process.

PMID- 20043608
TI  - Use of enhanced counterpulsation in the treatment of refractory angina pectoris
      and congestive heart failure.
AB  - Enhanced external counterpulsation (EECP) is a Food and Drug Administration
      approved non-pharmacological treatment for angina pectoris refractory to medical
      management and for use in the treatment of congestive heart failure. EECP
      improves quality of life, symptoms and exercise duration in these patients.

PMID- 20043609
TI  - Hemoptysis: diagnosis and treatment.
AB  - Hemoptysis is the expectoration of blood or blood tinged sputum from the bronchi,
      larynx, trachea or lungs. The etiology of hemoptysis is best categorized from the
      various system or site of bleeding. The management of hemoptysis begins with an
      initial assessment of gas exchange and hemodynamic stability followed by an
      identification of the cause by means of fiberoptic bronchoscopy, and chest
      imaging studies to attain cessation of bleeding and to prevent future recurrence.

PMID- 20043610
TI  - Parasympathetic nervous system and chronic facial dermatitis.
AB  - Recognizing the focal role of the CNS and stress in the pathogenesis of chronic
      facial dermatitis, the author hypothesized that the main responsibility for the
      persistence of CFD lies in the parasympathetic portion of the CNS. The validity
      of this hypothesis is challenged with organ specific treatments, leading to the
      resolution of parasympathetic stress and CFD.

PMID- 20043611
TI  - Diabetes--a silent disorder.
AB  - The earliest diagnosis of diabetes is a mandate to arrest the worldwide epidemic
      of diabetes. The insulin assay with the oral glucose tolerance provides the
      earliest diagnosis. The pathology of diabetes occurs in those with normal blood
      sugars. With earliest diagnosis, the 'diabetes epidemic' can be arrested and then
      reversed.

PMID- 20043612
TI  - Eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the
      esophagus characterized by abnormal infiltration of eosinophils. The incidence of
      the disease that occurs in children and adults has been rapidly increasing in the
      last decade. Diagnosis and management of EoE warrants consultation with an
      allergist and a gastroenterologist.

PMID- 20043613
TI  - The emerging role of highly sensitive troponin in the evaluation of acute
      coronary syndrome.
AB  - Cardiac troponin is the biomarker of choice for the serological diagnosis of
      acute myocardial infarction. With the development of "highly sensitive" troponin
      assays, it is now possible to measure levels of this marker at and below the
      current 99th percentile of a healthy population; high sensitive troponin assays
      show great potential in earlier detection of acute myocardial infarction and
      better risk prediction in patients with acute coronary syndrome.

PMID- 20043614
TI  - Hypersensitivity pneumonitis: evaluation and management.
AB  - Hypersensitivity pneumonitis consists of a group of diseases resulting from
      inhalation of organic particles causing an immunopathological reaction of the
      lungs in susceptible individuals. The diagnosis requires a detailed and careful
      history that would include social, environmental, and occupational status,
      pulmonary function tests, serum precipitins, bronchoalveolar lavage, imaging, and
      lung biopsy. Early recognition and avoidance of the causative agent is important
      although the use of corticosteroids hastens improvement of symptoms.

PMID- 20043615
TI  - Treatment of patients with supraventricular tachyarrhythmias in a medical
      intensive care unit.
AB  - Direct-current cardioversion has a higher success rate than does medical therapy
      in converting supraventricular tachyarrhythmias to sinus rhythm and should be
      performed immediately in patients with hemodynamic instability. Hemodynamically
      stable patients with atrial fibrillation or atrial flutter, a rapid ventricular
      rate and without preexcitation syndrome should be treated with intravenous beta
      adrenergic blocking drugs, amiodarone, verapamil, or diltiazem. In
      hemodynamically unstable patients with supraventricular tachycardia, intravenous
      adenosine is the drug of choice.

PMID- 20043616
TI  - ANCA-associated small vessel vasculitis (AASV) presenting as anemia and acute
      renal dysfunction.
AB  - AASV is an autoimmune disease with multiple-system involvement, which if
      untreated, carries a poor prognosis. The kidneys are the most common involved
      organ in these vasculitides. We present a case of AASV who presented with severe
      anemia and acute renal failure that was treated with steroids and
      cyclophosphamide.

PMID- 20043617
TI  - Hemoptysis in a patient with tracheopathia osteochondroplasia.
AB  - Tracheopathia osteochondroplasia is a rare slowly progressive benign disease of
      unknown etiology characterized by submucosal nodules protruding in the airway.
      Most patients are asymptomatic but with progression of disease, symptoms of
      cough, hemoptysis, dyspnea, wheezing, hoarseness, and rarely airway compromise
      have been reported. Management is symptomatic with control of cough, prophylaxis
      with antibiotics, and rarely surgery.

PMID- 20043619
TI  - Respiratory protection-preparing for H1N1 influenza.
AB  - This article alerts occupational health nurses to the issuance of new guidance
      from the Centers for Disease Control and Protection regarding respiratory
      protection when in contact with patients with confirmed or suspected H1N1 virus
      infection. Additionally, guidance from the Occupational Safety and Health
      Administration is provided for situations in which employers are unable to obtain
      sufficient supplies of disposable N95 respirators for which their personnel have
      been fit-tested.

PMID- 20043618
TI  - Nandrolone decanoate for the treatment of erythropoietin refractory anemia: a
      case series.
AB  - Erythropoietin refractory anemias represent a continuing and increasing burden on
      the healthcare system. The current practice of providing these patients with
      rHuEPO does not seem to be working. Fewer than 50% of patients respond in some
      studies. We demonstrate that androgens have multiple benefits in this population.
      They control anemia and stop transfusion dependence and improve nutritional
      parameters. In some patients, they also have a salutary effect on both white
      blood cell and platelet counts.

PMID- 20043620
TI  - An effective office ergonomic assessment and intervention program.
AB  - A significant portion of U.S. employees are office based and their work is
      sedentary. Office ergonomics is relevant to this population of employees to
      minimize the deleterious effects of static or sustained postures. Occupational
      health nurses currently conduct ergonomic assessments and provide interventions
      to decrease physical stressors. This article describes a straightforward process
      occupational health nurses can use to augment their ergonomic assessment and
      evaluation activities.

PMID- 20043621
TI  - Results of examinations conducted at a Japanese newspaper company and evaluation
      of changes in metabolic syndrome and lifestyle habits.
AB  - For purposes of developing effective occupational health nursing interventions,
      the authors clarified the long-term changes in health care data of employees in
      different departments at Company A, a Japanese newspaper company. Company A's
      clerical, sales, editing, and computer departments did not receive special
      occupational health activities; rather, health management centered on tertiary
      prevention provided through clinics. In this research, metabolic syndrome
      diagnostic standards were applied to all employees and changes in lifestyle risk
      factors over a period of 10 years were compared. The changes from 1998 to 2007
      were analyzed for each occupation, and a comparison between the 1998 and 2007
      groups was made using a paired t-test. Body mass index, the most significant
      indicator in the data, significantly increased in all departments. The
      researchers concluded it is essential to effectively manage employee health based
      on each occupation's work hours, tasks, and other work characteristics.

PMID- 20043622
TI  - Effects of extended work shifts and shift work on patient safety, productivity,
      and employee health.
AB  - It is estimated 1.3 million health care errors occur each year and of those
      errors 48,000 to 98,000 result in the deaths of patients (Barger et al., 2006).
      Errors occur for a variety of reasons, including the effects of extended work
      hours and shift work. The need for around-the-clock staff coverage has resulted
      in creative ways to maintain quality patient care, keep health care errors or
      adverse events to a minimum, and still meet the needs of the organization. One
      way organizations have attempted to alleviate staff shortages is to create
      extended work shifts. Instead of the standard 8-hour shift, workers are now
      working 10, 12, 16, or more hours to provide continuous patient care. Although
      literature does support these staffing patterns, it cannot be denied that shifts
      beyond the traditional 8 hours increase staff fatigue, health care errors, and
      adverse events and outcomes and decrease alertness and productivity. This article
      includes a review of current literature on shift work, the definition of shift
      work, error rates and adverse outcomes related to shift work, health effects on
      shift workers, shift work effects on older workers, recommended optimal shift
      length, positive and negative effects of shift work on the shift worker, hazards
      associated with driving after extended shifts, and implications for occupational
      health nurses.

PMID- 20043623
TI  - Gestational weight gain to promote optimal outcomes.
AB  - How much weight women gain during pregnancy, and their weight at conception, can
      affect their health and that of their babies.

PMID- 20043624
TI  - Copper(II)/copper(I)-catalyzed aza-Michael addition/click reaction of in situ
      generated alpha-azidohydrazones: synthesis of novel pyrazolone-triazole
      framework.
AB  - A one-pot Cu(II)-catalyzed aza-Michael addition of trimethylsilyl azide to 1,2
      diaza-1,3-dienes and Cu(I)-catalyzed 1,3-dipolar cycloaddition of in situ
      generated alpha-azidohydrazones with alkynes is reported. This process combining
      two consecutive steps with recycling of the catalyst (Cu(OAc)(2).H(2)O)
      represents a useful protocol for the smooth synthesis of novel pyrazolone
      triazole derivatives.

PMID- 20043625
TI  - Novel optical/electrochemical selective 1,2,3-triazole ring-appended chemosensor
      for the Al3+ ion.
AB  - A chemosensor (1) bearing a 1,2,3-triazole ring spacer was synthesized for the
      selective detection of Al(3+) with respect to dual optical and electrochemical
      changing events. The addition of Al(3+) ions to 1 induced a significant change in
      fluorescence intensity, attributable to ICT and CHEF effects from the 1,2,3
      triazole ring. The electrochemical behavior of 1 in the presence of the Al(3+)
      ion was significantly altered compared with those of the other metal cations
      tested.

PMID- 20043626
TI  - Anionic amino acid [closo-1-CB9H8-1-COO-10-NH3]- and dinitrogen acid [closo-1
      CB9H8-1-COOH-10-N2] as key precursors to advanced materials: synthesis and
      reactivity.
AB  - Amino acid [closo-1-CB(9)H(8)-1-COO-10-NH(3)](-) (4) was prepared by amination of
      iodo acid [closo-1-CB(9)H(8)-1-COOH-10-I](-) (1) with LiHMDS in a practical and
      reproducible manner. The apparent dissociation constants, pK(2) = 5.6 and pK(1) >
      11, were measured for 4[NMe(4)] in 50% aq. EtOH. Diazotization of 4 with
      NO(+)PF(6)(-) under mildly basic conditions afforded stable dinitrogen acid
      [closo-1-CB(9)H(8)-1-COOH-10-N(2)] (5). Activation parameters (DeltaH(++) = 33.9
      +/- 1.4 kcal mol(-1) and DeltaS(++) = 10 +/- 3.5 cal mol(-1) K(-1)) for
      thermolysis of its methyl ester [closo-1-CB(9)H(8)-1-COOMe-10-N(2)] (11) in PhCN
      were established, and the heterolysis of the B-N bond is believed to be the rate
      determining step. Electrochemical analysis showed a partially reversible
      reduction process for 11 (E(1/2)(red) = -1.03 V) and 5(-) (E(1/2)(red) = -1.21
      V), which are more cathodic than reduction of [closo-1-CB(9)H(9)-1-N(2)] (17).
      The dinitrogen acid 5 was reacted with pyridine and N,N-dimethylthioformamide, to
      form pyridine acid 6 and protected mercapto acid 7, respectively, through a
      boronium ylide intermediate 18. Compound 7 was converted to sulfonium acid 8. The
      molecular and crystal structures for 5 [C(2)H(9)B(9)N(2)O(2) monoclinic, P2(1)/n,
      a = 7.022(2) A, b = 11.389(4) A, c = 12.815(4) A, beta = 96.212(5) degrees ; V =
      1018.8(6) A(3), Z = 4,], 6 [C(7)H(14)B(9)NO(2), monoclinic, P2(1)/n, a =
      14.275(4) A, b = 12.184(3) A, c = 30.538(8) A, beta = 95.377(4) degrees ; V =
      5288(3) A(3), Z = 16], and 8 [C(7)H(19)B(9)O(2)S, monoclinic, P2(1)/c, a =
      15.988(5) A, b = 19.377(6) A, c = 9.655(3) A, beta = 98.348(5) degrees; V =
      2959.4(16) A(3), Z = 8] were determined by X-ray crystallography and compared
      with results of density functional theory (DFT) and MP2 calculations. Electronic
      structures of 5, 6, and related species were elucidated with electronic
      spectroscopy and assessed computationally at the B3LYP/6-31G(d,p), MP2/6
      31G(d,p), and ZINDO//MP2 levels of theory.

PMID- 20043627
TI  - Synthesis and highly selective bromination of Azacalix[4]pyrimidine macrocycles.
AB  - A number of N-substituted azacalix[4]pyrimidines were synthesized by two methods.
      While straightforward condensation reaction between 4,6-dichloropyrimidine and
      4,6-bis(alkylamino)pyrimidines gave identically N-substituted
      azacalix[4]pyrimidines in low yields, a general and moderate-to-high yielding 1 +
      3 macrocyclic fragment coupling reaction afforded azacalix[4]pyrimidines that
      contained either the same or different N-substituents. Upon treatment with N
      bromosuccinimide (NBS) under controlled conditions, methylazacalix[4]pyrimidine
      was selectively brominated at lower rim to produce mono-, di-, and tribrominated
      azacalix[4]pyrimidines in good yields. While azacalix[4]pyrimidine derivatives
      adopted 1,3-alternate conformation in the solid state, the synthesized
      macrocycles were fluxional in solution, and the interconversion of various
      conformational structures was rapid relative to the NMR time scale.

PMID- 20043628
TI  - Multigram-scale synthesis of short peptides via a simplified repetitive solution
      phase procedure.
AB  - A rapid repetitive solution-phase synthesis of peptides is described. The
      procedure involves coupling of amino acids and peptide acids, instead of the
      usual amino esters and peptide esters, to slight excesses of pentafluorophenyl
      active esters in a THF/water solvent mixture. Due to their poor solubility,
      peptide acid intermediates are easily isolated in high purity by acidification
      under controlled conditions and removal of excess active esters by selective
      extraction. Contrary to modern repetitive solution-phase peptide synthesis
      procedures, our approach does not require time-consuming neutralization reactions
      and reduces significantly the number of operation units that are necessary to
      obtain peptide intermediates. Efficiency of the method was demonstrated by the
      rapid synthesis of short hydrophobic and hydrophilic peptides, the antimalarial
      cycloheptapeptide mahafacyclin B, and a protected form of the hydrophilic
      pentapeptide GRGDS.

PMID- 20043629
TI  - One-pot electrosynthesis of substituted imidazolinium and tetrahydropyrimidinium
      salts from secondary alkyldiamines: an electrochemical route toward ionic
      liquids.
AB  - A one-pot electrosynthetic procedure has been developed to afford imidazolium and
      tetrahydropyrimidinium cationic derivatives from secondary alkyl diamines in
      neutral media. To this end, electrochemical oxidation of a series of aliphatic
      diamines (1-9) has been investigated. Mechanistic information is provided from
      analysis of the cyclic voltammetry data and identification of intermediate
      species and final products. The coexistence of two first-order chemical
      reactions, C(alpha)-H and C(alpha)-C(beta), at the radical cation level leading
      to identical final products is suggested to justify not only the nature but also
      the yields of the salts obtained.

PMID- 20043630
TI  - Unique diastereoselectivity trends in aminyl radical cyclizations onto silyl enol
      ethers.
AB  - The cyclization of nitrogen-centered radicals onto silyl enol ethers is an
      efficient method for the synthesis of polyhydroxylated alkaloids as the 2
      hydroxymethylpyrrolidine core can be readily accessed from a linear precursor.
      During our studies on the synthesis of polyhydroxylated alkaloid CYB-3, we found
      that the diastereoselectivity of the cyclization was dependent on a complex
      combination of sterics and olefin geometry. A more thorough understanding of the
      factors that lead to high diastereoselectivites would greatly expand the utility
      of this methodology in complex natural product synthesis. We have found that
      cyclization diastereoselectivities of substrates with alkyl or aryl substitution
      were excellent regardless of olefin geometry or substitution pattern. When
      electronegative substituents were introduced adjacent to the silyl enol ether,
      only Z-silyl enol ethers provide high diastereoselectivites. Temperature, steric
      size of the silyl group, and sterics and electronics of the metal hydride
      affected the selectivity to a lesser extent.

PMID- 20043631
TI  - Relationship of granule size distribution and amylopectin structure with pasting,
      thermal, and retrogradation properties in wheat starch.
AB  - Starches separated from 18 Indian wheat varieties were evaluated to see
      relationship of granule size distribution and amylopectin structure with pasting,
      thermal, and retrogradation properties. Average diameter of A-, B-, and C
      granules among different starches varied between 23.0 and 28.5, 10.0 and 12.0,
      and 2.3 and 2.7 mum, respectively. Amylopectin chain length distribution varied
      significantly, short length chains (DP 6-12) and long length chains (DP > 24)
      ranged between 44.5 and 52.4% and 3.7 and 6.5%, respectively, whereas amylose
      content ranged between 18.2 and 28.8%. Short length chains of amylopectin had
      inverse relationship with starch gelatinization temperatures T(o), T(p), and
      T(c). Starches with higher crystallinity had higher enthalpy of gelatinization
      and lower swelling power. Paste characteristics were mainly dependent upon
      granule type and all pasting parameters except pasting temperature, showed
      significant positive correlations with A-granules and negative with the
      proportion of B- and C-granule.

PMID- 20043632
TI  - Generation of free amino acids and gamma-aminobutyric acid in water-soaked
      soybean by high-hydrostatic pressure processing.
AB  - The effects of high-hydrostatic pressure processing (HPP) on soybean cotyledon as
      a cellular biological material were investigated from the viewpoints of the cell
      structure and enzyme reaction system. Damage to cell structure was evaluated by
      measuring dielectric properties using the Cole-Cole arc, the radius of which
      decreased as pressure level increased. Results suggested that cell structure was
      damaged by HPP. The distribution of free amino acids was measured after HPP (200
      MPa) of soybean soaked in water or sodium glutamate (Glu) solution. HPP resulted
      in high accumulation of free amino acids in water-soaked soybean, due to
      proteolysis. HPP of soybean in Glu solution caused higher accumulation of gamma
      aminobutyric acid, suggesting that both proteolysis and specific Glu metabolism
      were accelerated by HPP. We concluded that HPP partially degraded cell structure
      and accelerated biochemical reactions by allowing enzyme activities to remain.
      These events can be considered "high-pressure induced transformation" of soybean.

PMID- 20043633
TI  - Hydride, hydrogen, proton, and electron affinities of imines and their reaction
      intermediates in acetonitrile and construction of thermodynamic characteristic
      graphs (TCGs) of imines as a "molecule ID card".
AB  - A series of 61 imines with various typical structures were synthesized, and the
      thermodynamic affinities (defined as enthalpy changes or redox potentials in this
      work) of the imines to abstract hydride anions, hydrogen atoms, and electrons,
      the thermodynamic affinities of the radical anions of the imines to abstract
      hydrogen atoms and protons, and the thermodynamic affinities of the hydrogen
      adducts of the imines to abstract electrons in acetonitrile were determined by
      using titration calorimetry and electrochemical methods. The pure heterolytic and
      homolytic dissociation energies of the C=N pi-bond in the imines were estimated.
      The polarity of the C=N double bond in the imines was examined using a linear
      free-energy relationship. The idea of a thermodynamic characteristic graph (TCG)
      of imines as an efficient "Molecule ID Card" was introduced. The TCG can be used
      to quantitatively diagnose and predict the characteristic chemical properties of
      imines and their various reaction intermediates as well as the reduction
      mechanism of the imines. The information disclosed in this work could not only
      supply a gap of thermodynamics for the chemistry of imines but also strongly
      promote the fast development of the applications of imines.

PMID- 20043635
TI  - Alternative reaction mechanism for the cross-linking of gelatin with
      glutaraldehyde.
AB  - FT-IR, in combination with residual amino group determination using a
      fluorescence technique, has been used to investigate the chemical functional
      groups involved in the cross-linking reaction between glutaraldehyde and gelatin
      molecules. The results suggest that, at high pH values (i.e., close to the pK(a)
      of lysine), the cross-linking reaction is mainly governed by the well-known
      Schiff base formation, whereas at low pH (i.e., when the amino groups of lysine
      are protonated), the reaction may also involve the -OH groups of hydroxyproline
      and hydroxylysine, leading to the formation of hemiacetals.

PMID- 20043634
TI  - Bioinspired materials for controlling stem cell fate.
AB  - Although researchers currently have limited ability to mimic the natural stem
      cell microenvironment, recent work at the interface of stem biology and
      biomaterials science has demonstrated that control over stem cell behavior with
      artificial microenvironments is quite advanced. Embryonic and adult stem cells
      are potentially useful platforms for tissue regeneration, cell-based
      therapeutics, and disease-in-a-dish models for drug screening. The major
      challenge in this field is to reliably control stem cell behavior outside the
      body. Common biological control schemes often ignore physicochemical parameters
      that materials scientists and engineers commonly manipulate, such as substrate
      topography and mechanical and rheological properties. However, with appropriate
      attention to these parameters, researchers have designed novel synthetic
      microenvironments to control stem cell behavior in rather unnatural ways. In this
      Account, we review synthetic microenvironments that aim to overcome the
      limitations of natural niches rather than to mimic them. A biomimetic stem cell
      control strategy is often limited by an incomplete understanding of the complex
      signaling pathways that drive stem cell behavior from early embryogenesis to late
      adulthood. The stem cell extracellular environment presents a miscellany of
      competing biological signals that keep the cell in a state of unstable
      equilibrium. Using synthetic polymers, researchers have designed synthetic
      microenvironments with an uncluttered array of cell signals, both specific and
      nonspecific, that are motivated by rather than modeled after biology. These have
      proven useful in maintaining cell potency, studying asymmetric cell division, and
      controlling cellular differentiation. We discuss recent research that highlights
      important biomaterials properties for controlling stem cell behavior, as well as
      advanced processes for selecting those materials, such as combinatorial and high
      throughput screening. Much of this work has utilized micro- and nanoscale
      fabrication tools for controlling material properties and generating diversity in
      both two and three dimensions. Because of their ease of synthesis and similarity
      to biological soft matter, hydrogels have become a biomaterial of choice for
      generating 3D microenvironments. In presenting these efforts within the framework
      of synthetic biology, we anticipate that future researchers may exploit synthetic
      polymers to create microenvironments that control stem cell behavior in
      clinically relevant ways.

PMID- 20043636
TI  - Functional characteristics of egg white proteins within wheat, rye, and
      germinated-rye sourdoughs.
AB  - Egg white (EW) proteins are functional proteins, which possess certain biological
      activities (antimicrobial, antigenic, and peptidase-inhibitory) that may
      influence the food processing or vice versa can be affected by processing. This
      study investigated the behavior of EW proteins within sourdough systems with
      respect to proteolysis and fermentation parameters, and the ability of EW to
      build foam structures with sourdoughs. Of the EW proteins, ovotransferrin was
      hydrolyzed in all sourdoughs (wheat, rye, and germinated-rye), whereas the
      breakdown of ovalbumin was specific for germinated-rye sourdoughs, with the
      cysteine endopeptidases being responsible for the hydrolysis. The presence of EW
      in sourdough fermentations had no influence on the prolamin hydrolysis or the
      growth of starter culture, indicating that the peptidase-inhibitory and
      antimicrobial properties of EW play no important role in sourdoughs. EW foams,
      however, appeared as potential structure builders in sourdough applications and
      could serve as alternative structural agents in the production of baked goods
      with low gluten content.

PMID- 20043637
TI  - Quantification of branched chain fatty acids in polar and neutral lipids of
      cheese and fish samples.
AB  - Branched chain fatty acids (iso- and anteiso-fatty acids) are common minor
      compounds of the lipids found in dairy products and fish (<1-3%) and major fatty
      acids of Gram-positive bacteria. Their presence in food has been associated with
      bacterial sources. Bacterial lipids usually consist of polar lipids and virtually
      no triacylglycerides while food lipids are predominantly composed of
      triacylglycerides. In this study, we examined the difference in the iso- or
      anteiso-fatty acid content and composition of neutral and polar lipids in fish
      and cheese samples. Neutral lipids (triacylglycerides) were separated from the
      polar lipids (phospholipids) by means of solid-phase extraction (SPE). Deuterium
      labeled internal standards were used to verify the successful performance of the
      accelerated solvent extraction and particularly the SPE. The separated lipid
      fractions were transformed into their corresponding fatty acid methyl esters, and
      the concentrations of seven iso- and anteiso-fatty acids were determined by means
      of gas chromatography coupled to electron ionization mass spectrometry operated
      in the selected ion monitoring mode (GC/EI-MS-SIM). No coelutions of branched
      chain fatty acids with other fatty acids were obtained on the medium polar column
      used for quantification. The branched chain fatty acid content of 17 cheese and 7
      fish samples ranged between 0.2% and 1.9% in polar lipids and between 0.1% and
      1.7% in neutral lipids. The concentration of total branched chain fatty acids in
      fish was 2-10 times lower than that found in cheeses, and the relative
      distribution of iso-17:0 and iso-15:0 increased compared to their anteiso
      homologues. While branched chain fatty acids in polar lipids of cheese
      constituted only approximately 1% of the content in total lipids, their
      contribution in fish was significantly higher (6% to >30%).

PMID- 20043638
TI  - Synthesis and structure-activity relationships of azamacrocyclic C-X-C chemokine
      receptor 4 antagonists: analogues containing a single azamacrocyclic ring are
      potent inhibitors of T-cell tropic (X4) HIV-1 replication.
AB  - Bis-tetraazamacrocycles such as the bicyclam AMD3100 (1) are a class of potent
      and selective anti-HIV-1 agents that inhibit virus replication by binding to the
      chemokine receptor CXCR4, the coreceptor for entry of X4 viruses. By sequential
      replacement and/or deletion of the amino groups within the azamacrocyclic ring
      systems, we have determined the minimum structural features required for potent
      antiviral activity in this class of compounds. All eight amino groups are not
      required for activity, the critical amino groups on a per ring basis are
      nonidentical, and the overall charge at physiological pH can be reduced without
      compromising potency. This approach led to the identification of several single
      ring azamacrocyclic analogues such as AMD3465 (3d), 36, and 40, which exhibit
      EC(50)'s against the cytopathic effects of HIV-1 of 9.0, 1.0, and 4.0 nM,
      respectively, antiviral potencies that are comparable to 1 (EC(50) against HIV-1
      of 4.0 nM). More importantly, however, the key structural elements of 1 required
      for antiviral activity may facilitate the design of nonmacrocyclic CXCR4
      antagonists suitable for HIV treatment via oral administration.

PMID- 20043639
TI  - Kinetics of electron transfer reactions of H2-evolving cobalt diglyoxime
      catalysts.
AB  - Co-diglyoxime complexes catalyze H(2) evolution from protic solutions at modest
      overpotentials. Upon reduction to Co(I), a Co(III)-hydride is formed by reaction
      with a proton donor. Two pathways for H(2) production are analyzed: one is a
      heterolytic route involving protonation of the hydride to release H(2) and
      generate Co(III); the other is a homoytic pathway requiring association of two
      Co(III)-hydrides. Rate constants and reorganization parameters were estimated
      from analyses of laser flash-quench kinetics experiments (Co(III)-Co(II) self
      exchange k = 9.5 x 10(-8) - 2.6 x 10(-5) M(-1) s(-1); lambda = 3.9 (+/-0.3) eV:
      Co(II)-Co(I) self-exchange k = 1.2 (+/-0.5) x 10(5) M(-1) s(-1); lambda = 1.4 (+/
      0.05) eV). Examination of both the barriers and driving forces associated with
      the two pathways indicates that the homolytic reaction (Co(III)H + Co(III)H --> 2
      Co(II) + H(2)) is favored over the route that goes through a Co(III) intermediate
      (Co(III)H + H(+) --> Co(III) + H(2)).

PMID- 20043641
TI  - Facile cyclization of terphenyl to triphenylene: a new chemodosimeter for
      fluoride ions.
AB  - Terphenyl derivatives 3 and 4 having OTBS groups have been synthesized via a
      Suzuki-Miyura coupling reaction. These compounds undergo unprecedented
      irreversible cyclization to symmetrically/unsymmetrically substituted
      triphenylenes while carrying out the deprotection of OTBS groups using
      tetrabutylammonium fluoride. Terphenyl 3 also serves as a new chemodosimeter for
      fluoride ions.

PMID- 20043640
TI  - Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide
      nanoparticle through iron doping.
AB  - The establishment of verifiably safe nanotechnology requires the development of
      assessment tools to identify hazardous nanomaterial properties that could be
      modified to improve nanomaterial safety. While there is a lot of debate of what
      constitutes appropriate safety screening methods, one approach is to use the
      assessment of cellular injury pathways to collect knowledge about hazardous
      material properties that could lead to harm to humans and the environment. We
      demonstrate the use of a multiparameter cytotoxicity assay that evaluates toxic
      oxidative stress to compare the effects of titanium dioxide (TiO(2)), cerium
      oxide (CeO(2)), and zinc oxide (ZnO) nanoparticles in bronchial epithelial and
      macrophage cell lines. The nanoparticles were chosen on the basis of their volume
      of production and likelihood of spread to the environment. Among the materials,
      dissolution of ZnO nanoparticles and Zn(2+) release were capable of ROS
      generation and activation of an integrated cytotoxic pathway that includes
      intracellular calcium flux, mitochondrial depolarization, and plasma membrane
      leakage. These responses were chosen on the basis of the compatibility of the
      fluorescent dyes that contemporaneously assess their response characteristics by
      a semiautomated epifluorescence procedure. Purposeful reduction of ZnO
      cytotoxicity was achieved by iron doping, which changed the material matrix to
      slow Zn(2+) release. In summary, we demonstrate the utility of a rapid
      throughput, integrated biological oxidative stress response pathway to perform
      hazard ranking of a small batch of metal oxide nanoparticles, in addition to
      showing how this assay can be used to improve nanosafety by decreasing ZnO
      dissolution through Fe doping.

PMID- 20043642
TI  - Switching the chemoselectivity in the amination of 4-chloroquinazolines with
      aminopyrazoles.
AB  - The chemoselectivity in the amination of 4-chloroquinazolines with 3-amino-1H
      pyrazoles was studied. Under the conditions of Pd(2)(dba)(3)/Xantphos/Na(2)CO(3),
      4-chloroquinazolines underwent selective amination with the cyclic secondary
      amino group of 3-amino-1H-pyrazoles, whereas 4-chloroquinazolines were
      exclusively aminated with the primary amino group of 3-amino-1H-pyrazoles via
      S(N)Ar substitution in the presence of HCl.

PMID- 20043643
TI  - Label-free femtomolar detection of target DNA by impedimetric DNA sensor based on
      poly(pyrrole-nitrilotriacetic acid) film.
AB  - An ultrahigh performance impedimetric DNA sensor is presented showing detection
      limits in the femtomolar range. This electrochemical setup was constructed
      initially by electrogeneration of poly(11-pyrrol-1-yl-undecanoic acid
      N(alpha'),N(alpha)-bis(carboxymethyl)-L-lysine amide) (poly(pyrrole-NTA)) film.
      The latter was then modified by the coordination of Cu(2+) ions onto the
      chelating NTA centers followed by the immobilization of the ssHIV-DNA previously
      modified by a polyhistidine tag by affinity binding. The immobilization of the
      DNA probe and hybridization with the complementary target ssHIV-DNA were
      investigated using fluorescence microscopy and quantified with quartz crystal
      microbalance experiments leading to DNA probe and duplex coverage of 1.7 x 10(
      11) and 7.7 x 10(-12) mol cm(-2), respectively. The duplex formation was
      corroborated by amperometric measurements through the duplex labeling by a
      glucose oxidase. In the presence of hydroquinone as redox indicator, the DNA
      sensor was applied to the impedimetric detection of target DNA without a labeling
      step. A linear quantification of the HIV DNA target was carried out in the range
      10(-15) to 10(-8) mol L(-1).

PMID- 20043644
TI  - Ruthenium catalyzed directing group-free C2-selective carbenoid functionalization
      of indoles by alpha-aryldiazoesters.
AB  - A directing group-free approach for C2-selective carbenoid functionalization of
      NH-indoles is presented. Using [RuCl(2)(p-cymene)](2) as catalyst and alpha
      aryldiazoesters as carbenoid source, 2-alkylated indoles were obtained in up to
      96% isolated yield. Similarly, a regioselective carbenoid functionalization of NH
      pyrroles was also achieved.

PMID- 20043645
TI  - Identification of furan metabolites derived from cysteine-cis-2-butene-1,4-dial
      lysine cross-links.
AB  - Furan is a rodent hepatotoxicant and carcinogen. Because this compound is an
      important industrial intermediate and has been detected in heat-processed foods
      and smoke, humans are likely exposed to this toxic compound. Characterization of
      urinary metabolites of furan will lead to the development of biomarkers to assess
      human health risks associated with furan exposure. Previous studies indicate that
      furan is oxidized to a reactive alpha,beta-unsaturated dialdehyde, cis-2-butene
      1,4-dial (BDA), in a reaction catalyzed by cytochrome P450. Five previously
      characterized metabolites are derived from the reaction of BDA with cellular
      nucleophiles such as glutathione and protein. They include the monoglutathione
      reaction product, N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-l
      cysteinylglycine cyclic sulfide, and its downstream metabolite, S-[1-(1,3
      dicarboxypropyl)-1H-pyrrol-3-yl]methylthiol, as well as (R)-2-acetylamino-6-(2,5
      dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid and N-acetyl-S-[1-(5-acetylamino-5
      carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine and its sulfoxide. The last two
      compounds are downstream metabolites of a BDA-derived cysteine-lysine cross-link,
      S-[1-(5-amino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine. In this report, we
      present the characterization of seven additional urinary furan metabolites, all
      of which are derived from this cross-link. The cysteinyl residue is subject to
      several biotransformation reactions, including N-acetylation and S-oxidation.
      Alternatively, it can undergo beta-elimination followed by S-methylation to a
      methylthiol intermediate that is further oxidized to a sulfoxide. The lysine
      portion of the cross-link either is N-acetylated or undergoes a transamination
      reaction to generate an alpha-ketoacid metabolite that undergoes oxidative
      decarboxylation. Some of these metabolites are among the most abundant furan
      metabolites present in urine as judged by LC-MS/MS analysis, indicating that the
      oxidation of furan to BDA and BDA's subsequent reaction with cellular cysteine
      and lysine residues may represent a significant in vivo pathway of furan
      biotransformation. Because they are derived from cellular BDA reaction products,
      these metabolites are markers of furan exposure and bioactivation and could be
      explored as potential biomarkers in human studies.

PMID- 20043646
TI  - Site-specific protein adducts of 4-hydroxy-2(E)-nonenal in human THP-1 monocytic
      cells: protein carbonylation is diminished by ascorbic acid.
AB  - The protein targets and sites of modification by 4-hydroxy-2(E)-nonenal (HNE) in
      human monocytic THP-1 cells after exogenous exposure to HNE were examined using a
      multipronged proteomic approach involving electrophoretic, immunoblotting, and
      mass spectrometric methods. Immunoblot analysis using monoclonal anti-HNE
      antibodies showed several proteins as targets of HNE adduction. Pretreatment of
      THP-1 cells with ascorbic acid resulted in reduced levels of HNE-protein adducts.
      Biotinylation of Michael-type HNE adducts using an aldehyde-reactive
      hydroxylamine-functionalized probe (aldehyde-reactive probe, ARP) and subsequent
      enrichment facilitated the identification and site-specific assignment of the
      modifications by LC-MS/MS analysis. Sixteen proteins were unequivocally
      identified as targets of HNE adduction, and eighteen sites of HNE modification at
      Cys and His residues were assigned. HNE exposure of THP-1 cells resulted in the
      modification of proteins involved in cytoskeleton organization and regulation,
      proteins associated with stress responses, and enzymes of the glycolytic and
      other metabolic pathways. This study yielded the first evidence of site-specific
      adduction of HNE to Cys-295 in tubulin alpha-1B chain, Cys-351 and Cys-499 in
      alpha-actinin-4, Cys-328 in vimentin, Cys-369 in D-3-phosphoglycerate
      dehydrogenase, and His-246 in aldolase A.

PMID- 20043648
TI  - Solid-solid phase transitions in DL-norvaline studied by differential scanning
      calorimetry and Raman spectroscopy.
AB  - The structural modifications of the amino acid DL-Norvaline have been studied
      using differential scanning calorimetry (DSC) and Raman spectroscopy. DSC results
      showed that this amino acid undergoes two solid-solid phase transitions at -116.9
      and -76.1 degrees C in the temperature range -130 to +300 degrees C. Raman
      spectroscopy was applied to complement DSC results. The combination of the two
      methodologies point out that the observed phase transitions correspond to an
      increment of disordering in the aliphatic side chain of amino acid, an
      augmentation of the rotational motion of the amino group and a decrease of the
      strength of the intramolecular hydrogen bonding of the initial dimers at low
      temperatures. The observed phase transitions of DL-norvaline are compared with
      those found in DL-norleucine.

PMID- 20043647
TI  - Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density
      lipoprotein.
AB  - Accumulation of low-density lipoprotein (LDL)-derived cholesterol by artery wall
      macrophages triggers atherosclerosis, the leading cause of cardiovascular
      disease. Conversely, high-density lipoprotein (HDL) retards atherosclerosis by
      promoting cholesterol efflux from macrophages by the membrane-associated ATP
      binding cassette transporter A1 (ABCA1) pathway. HDL has been proposed to lose
      its cardioprotective effects in subjects with atherosclerosis, but the underlying
      mechanisms are poorly understood. One potential pathway involves oxidative damage
      by myeloperoxidase (MPO), a heme enzyme secreted by human artery wall
      macrophages. We used mass spectrometry to demonstrate that HDL isolated from
      patients with established cardiovascular disease contains elevated levels of 3
      chlorotyrosine and 3-nitrotyrosine, two characteristic products of MPO. When
      apolipoprotein A-I (apoA-I), the major HDL protein, was oxidized by MPO, its
      ability to promote cellular cholesterol efflux by ABCA1 was impaired. Moreover,
      oxidized apoA-I was unable to activate lecithin:cholesterol acyltransferase
      (LCAT), which rapidly converts free cholesterol to cholesteryl ester, a critical
      step in HDL maturation. Biochemical studies implicated tyrosine chlorination and
      methionine oxygenation in the loss of ABCA1 and LCAT activity by oxidized apoA-I.
      Oxidation of specific residues in apoA-I inhibited two key steps in cholesterol
      efflux from macrophages, raising the possibility that MPO initiates a pathway for
      generating dysfunctional HDL in humans.

PMID- 20043649
TI  - Theory and normal-mode analysis of change in protein vibrational dynamics on
      ligand binding.
AB  - The change of protein vibrations on ligand binding is of functional and
      thermodynamic importance. Here, this process is characterized using a simple
      analytical "ball-and-spring" model and all-atom normal-mode analysis (NMA) of the
      binding of the cancer drug, methotrexate (MTX) to its target, dihydrofolate
      reductase (DHFR). The analytical model predicts that the coupling between protein
      vibrations and ligand external motion generates entropy-rich, low-frequency
      vibrations in the complex. This is consistent with the atomistic NMA which
      reveals vibrational softening in forming the DHFR-MTX complex, a result also in
      qualitative agreement with neutron-scattering experiments. Energy minimization of
      the atomistic bound-state (B) structure while gradually decreasing the ligand
      interaction to zero allows the generation of a hypothetical "intermediate" (I)
      state, without the ligand force field but with a structure similar to that of B.
      In going from I to B, it is found that the vibrational entropies of both the
      protein and MTX decrease while the complex structure becomes enthalpically
      stabilized. However, the relatively weak DHFR:MTX interaction energy results in
      the net entropy gain arising from coupling between the protein and MTX external
      motion being larger than the loss of vibrational entropy on complex formation.
      This, together with the I structure being more flexible than the unbound
      structure, results in the observed vibrational softening on ligand binding.

PMID- 20043650
TI  - Photoinduced control over the self-organized orientation of amorphous molecular
      materials using polarized light.
AB  - Novel chiral amorphous molecular materials containing photoresponsive azobenzene
      moieties were designed and synthesized. These materials led to the formation of
      smooth and uniform thin films without grain boundaries. Photoirradiation of the
      thin film with linearly and elliptically polarized light caused trans-cis
      photoisomerization of the azobenzene moieties and resulted in an anisotropic
      orientation of the materials. Maximum change in a value of birefringence, Deltan,
      after irradiation of the linearly polarized light is about 0.08 with a response
      time of 10 s. However, when irradiation was ceased after photoinduced
      orientation, the value of Deltan decreased due to relaxation of the azobenzene
      moieties. Furthermore, these materials exhibited a high efficiency of a
      photoinduced polarization rotation over 30 deg mum(-1) after irradiation with the
      elliptically polarized light for 60 s. We also found that the efficiency depends
      on ellipticity of the incident light and on the thickness of the sample. The
      origin of the large change in the molecular orientation is the anisotropic
      arrangement of the azobenzenes in the terminal groups upon irradiation with the
      linearly and elliptically polarized light.

PMID- 20043651
TI  - Real-time partitioning of octadecyl rhodamine B into bead-supported lipid bilayer
      membranes revealing quantitative differences in saturable binding sites in DOPC
      and 1:1:1 DOPC/SM/cholesterol membranes.
AB  - Quantitative analysis of the staining of cell membranes with the cationic
      amphiphile, octadecyl rhodamine B (R18), is confounded by probe aggregation and
      changes to the probes' absorption cross section and emission quantum yield. In
      this paper, flow cytometry, quantum-dot-based fluorescence calibration beads, and
      FRET were used to examine real-time transfer of R18 from water to two limiting
      models of the cellular plasma membrane, namely, a single-component disordered
      membrane, dioleoyl-L-alpha-phosphatidylcholine (DOPC), and a ternary mixture of
      DOPC, cholesterol, and sphingomyelin (DSC) membranes, reconstituted on spherical
      and monodisperse glass beads (lipobeads). The quenching of R18 was analyzed as
      the probe concentration was raised from 0 to 10 mol % in membranes. The data show
      a > 2-fold enhancement in the quenching level of the probes that were
      reconstituted in DSC relative to DOPC membranes at the highest concentration of
      R18. We have parametrized the propagation of concentration-dependent quenching as
      a function of real-time binding of R18 to lipobeads. In this way,
      phenomenological kinetics of serum-albumin-mediated transfer of R18 from the
      aqueous phase to DOPC and DSC membranes could be evaluated under optimal
      conditions where the critical aggregation concentration (CAC) of the probe is
      defined as 14 nM. The mass action kinetics of association of R18 with DOPC and
      DSC lipobeads are shown to be similar. However, the saturable capacity for
      accepting exogenous probes is found to be 37% higher in DOPC relative to that for
      DSC membranes. The difference is comparable to the disparity in the average
      molecular areas of DOPC and DSC membranes. Finally, this analysis shows little
      difference in the spectral overlap integrals of the emission spectrum of a
      fluorescein derivative donor and the absorption spectrum of either monomeric or
      simulated spectrum of dimeric R18. This approach represents a first step toward a
      nanoscale probing of membrane heterogeneity in living cells by analyzing
      differential local FRET among sites of unique receptor expression in living
      cells.

PMID- 20043653
TI  - On the denaturation mechanisms of the ligand binding domain of thyroid hormone
      receptors.
AB  - The ligand binding domain (LBD) of nuclear hormone receptors adopts a very
      compact, mostly alpha-helical structure that binds specific ligands with very
      high affinity. We use circular dichroism spectroscopy and high-temperature
      molecular dynamics simulations to investigate unfolding of the LBDs of thyroid
      hormone receptors (TRs). A molecular description of the denaturation mechanisms
      is obtained by molecular dynamics simulations of the TRalpha and TRbeta LBDs in
      the absence and in the presence of the natural ligand Triac. The simulations show
      that the thermal unfolding of the LBD starts with the loss of native contacts and
      secondary structure elements, while the structure remains essentially compact,
      resembling a molten globule state. This differs from most protein denaturation
      simulations reported to date and suggests that the folding mechanism may start
      with the hydrophobic collapse of the TR LBDs. Our results reveal that the
      stabilities of the LBDs of the TRalpha and TRbeta subtypes are affected to
      different degrees by the binding of the isoform selective ligand Triac and that
      ligand binding confers protection against thermal denaturation and unfolding in a
      subtype specific manner. Our simulations indicate two mechanisms by which the
      ligand stabilizes the LBD: (1) by enhancing the interactions between H8 and H11,
      and the interaction of the region between H1 and the Omega-loop with the core of
      the LBD, and (2) by shielding the hydrophobic H6 from hydration.

PMID- 20043652
TI  - A simple and mild synthesis of 1H-isochromenes and (Z)-1-alkylidene-1,3
      dihydroisobenzofurans by the iodocyclization of 2-(1-alkynyl)benzylic alcohols.
AB  - A variety of iodo-substituted isochromenes, dihydroisobenzofurans, and
      pyranopyridines are readily prepared in good to excellent yields under mild
      conditions by the iodocyclization of readily available 2-(1-alkynyl)benzylic
      alcohols or 2-(1-alkynyl)-3-(hydroxymethyl)pyridines. Reactions are carried out
      in MeCN at 25 degrees C with 3 equiv of I(2) as the iodine source and NaHCO(3) (3
      equiv) as the base. The regiochemical outcome of the reaction strongly depends on
      the substitution pattern of the starting material. In particular, the 5-exo-dig
      cyclization mode, leading to dihydroisobenzofurans, is observed in the case of
      substrates bearing a tertiary alcoholic group, owing to the gem-dialkyl effect,
      while the 6-endo-dig cyclization mode, leading to isochromene or pyranopyridines,
      is the usually preferred pathway in the case of substrates bearing a primary or
      secondary alcoholic group.

PMID- 20043654
TI  - Conformational sampling of influenza fusion peptide in membrane bilayers as a
      function of termini and protonation states.
AB  - Influenza fusion peptide is critical for mediating the fusion of viral and host
      cell membranes during viral entry. The interaction of monomeric influenza fusion
      peptide with membranes is studied with replica exchange molecular dynamics
      simulations using a new implicit membrane model to effectively reach microsecond
      to millisecond time scales. The conformational sampling of the fusion peptide was
      studied as a function of different N- and C-termini, including an experimental
      construct with an additional C-terminal tag, as well as a function of protonation
      of acidic residues. It is found that the influenza fusion peptide mostly adopts
      helical structures with a pronounced kink at residues 11-13 with both N-terminal
      and C-terminal helices oriented mostly parallel to the membrane surface. A
      charged C-terminus and the presence of a charge C-terminal tag significantly
      alters the conformational sampling of the fusion peptide and results in more
      diverse conformational ensembles that include obliquely inserted N-terminal
      peptide structures. Protonation of acidic residues also affects the
      conformational sampling, however, based on pK(a) shift estimates the overall
      effect of pH = 5 on the conformational sampling of the influenza fusion peptide
      appears to be only minor.

PMID- 20043655
TI  - Enhanced gold nanoparticle based ELISA for a breast cancer biomarker.
AB  - In this work, we developed an optical enzyme-linked immunosorbent assay (ELISA)
      immunoassay for the analysis of CA15-3 antigen, an important biomarker present in
      blood samples and useful for the follow-up of the medical treatment of breast
      cancer. Gold nanoparticles (AuNPs) were used as carriers of the signaling
      antibody anti-CA15-3-HRP (horseradish peroxidase) in order to achieve an
      amplification of the optical signal. In the range between 0 and 60 U/mL, the
      assay adopting AuNPs as an enhancer resulted in higher sensitivity and shorter
      assay time when compared to classical ELISA procedures. The application of AuNPs
      to the commercially available ELISA test can be useful to improve important
      immunoanalysis procedures where a more confident result is needed.

PMID- 20043656
TI  - C60+ secondary ion microscopy using a delay line detector.
AB  - Buckminsterfullerene (C(60)) as a primary ion for secondary ion mass spectrometry
      (SIMS) has shown many benefits over classical SIMS sources in the analysis of
      large organic molecules including many of biological significance. One constraint
      has been the limited focusing capabilities of the C(60)(+) beam. Although this
      could be circumvented by using beam size limiting apertures at the cost of beam
      current, high-resolution imaging using conventional time-of-flight (TOF)
      instruments has been challenging and time-consuming. We present a method in which
      we combine the use of an unfocused C(60)(+) beam with an ion optical microscope.
      A delay line detector is used to obtain fully resolved hyperspectral data sets
      that contain both the full mass spectral and the localization information. The
      obtained image resolving power is 4 microm at a pixel size of 250 nm. Microscope
      mode C(60)(+) imaging was shown to resolve micrometer-scale features in a
      combined polymer-tissue sample. Our new approach demonstrates high-quality SIMS
      imaging using the full C(60)(+) beam current. This results in equal or better
      resolving power at reduced acquisition speed.

PMID- 20043657
TI  - Computational studies of structural, electronic, spectroscopic, and thermodynamic
      properties of methylmercury-amino acid complexes and their Se analogues.
AB  - Quantum chemical calculations have been carried out to study the structural,
      electronic, spectroscopic, and thermodynamic properties of five methylmercury
      amino acid complexes and their selenium analogues. The structural properties of
      methylmercury-amino acids are very similar to their Se analogues except for those
      properties that are directly related to the Se atom which has a larger covalent
      radius. Characteristic stretching frequencies are observed for Hg-S/Se and Hg-C
      bonds. Electronic properties of both methylmercury-amino acids and their Se
      analogues are different from each other, with the S complexes showing stronger
      electrostatic attractions which leads to stronger bonds to mercury. The
      methylmercury complexes with selenoamino complexes, however, are
      thermodynamically more favorable (DeltaG of formation from suitable model
      reactants) than those of the corresponding amino acid complexes. This can be
      traced to the lower stability of the reactant selenoamino acids. Such different
      stability and favorability of formation might be responsible for the different
      physiological activity in biological systems such as the Hg-Se antagonism.

PMID- 20043658
TI  - Substituent effects in ion-pi interactions: fine-tuning via the ethynyl group.
AB  - In this work, we report a high level theoretical study (RI-MP2(full)/aug-cc-pVDZ)
      that deals with the effect of electron-withdrawing substituents on cation-pi and
      anion-pi interactions in the absence/presence of triple bonds between the
      substituent and the aromatic ring. The ethynyl group is able to finely tune the
      interaction energy of the complexes. Interestingly, for the cation-pi complexes,
      it reduces the effect of the electron withdrawing groups (EWG), improving the
      interaction. For anion-pi complexes, it boosts the effect of the EWG, improving
      the interaction as well. This dual behavior has been studied by examining the
      geometric and energetic features of the complexes, "atoms-in-molecules" analysis
      and charge transfer effects.

PMID- 20043659
TI  - Ultrafast dynamics in helium nanodroplets probed by femtosecond time-resolved EUV
      photoelectron imaging.
AB  - The dynamics of electronically excited helium nanodroplets are studied by
      femtosecond time-resolved photoelectron imaging. EUV excitation into a broad
      absorption band centered around 23.8 eV leads to an indirect photoemission
      process that generates ultraslow photoelectrons. A 1.58 eV probe pulse
      transiently depletes the indirect photoemission signal for pump-probe time delays
      <200 fs and enhances the signal beyond this delay. The depletion is due to
      suppression of the indirect ionization process by the probe photon, which
      generates a broad, isotropically emitted photoelectron band. Similar time scales
      in the decay of the high energy photoelectron signal and the enhancement of the
      indirect photoemission signal suggest an internal relaxation process that
      populates states in the range of a lower energy droplet absorption band located
      just below the droplet ionization potential (IP approximately 23.0 eV). A nearly
      70% enhancement of the ultraslow photoelectron signal indicates that interband
      relaxation plays a more dominant role for the droplet de-excitation mechanism
      than photoemission.

PMID- 20043660
TI  - Van der waals interactions in molecular assemblies from first-principles
      calculations.
AB  - We investigated intermolecular interactions in weakly bonded molecular assemblies
      from first principles, by combining exact exchange energies (EXX) with
      correlation energies defined by the adiabatic connection fluctuation-dissipation
      theorem, within the random phase approximation (RPA). We considered three
      different types of molecular systems: the benzene crystal, the methane crystal,
      and self-assembled monolayers of phenylenediisocyanide, which involve aromatic
      rings, sp(3)-hybridized C-H bonds, and isocyanide triple bonds, respectively. We
      describe in detail how computed equilibrium lattice constants and cohesive
      energies may be affected by the input ground state wave functions and orbital
      energies, by the geometries of molecular monomers in the assemblies, and by the
      inclusion of zero-point energy contribution to the total energy. We find that the
      EXX/RPA perturbative approach provides an overall satisfactory, first-principles
      description of dispersion forces. However, binding energies tend to be
      underestimated, and possible reasons for this discrepancy are discussed.

PMID- 20043661
TI  - Collective fluorescence blinking in linear J-aggregates assisted by long-distance
      exciton migration.
AB  - Fluorescence blinking corresponding to collective quenching of up to 100 dye
      monomers is reported for individual J-aggregates of a perylene bisimide (PBI)
      dye. This implies an exciton diffusion length up to 70 nm in these one
      dimensional assemblies. The number of quenched monomers was directly measured by
      comparing the fluorescence brightness of the J-aggregates with that of noncoupled
      PBI molecules. This brightness analysis technique is useful for unraveling
      photophysical parameters of any individual fluorescent nanosystem.

PMID- 20043662
TI  - Shape effect of carbon nanovectors on angiogenesis.
AB  - Physically diverse carbon nanostructures are increasingly being studied for
      potential applications in cancer chemotherapy. However, limited knowledge exists
      on the effect of their shape in tuning the biological outcomes when used as
      nanovectors for drug delivery. In this study, we evaluated the effect of
      doxorubicin-conjugated single walled carbon nanotubes (CNT-Dox) and doxorubicin
      conjugated spherical polyhydroxylated fullerenes or fullerenols (Ful-Dox) on
      angiogenesis. We report that CNTs exert a pro-angiogenic effect in vitro and in
      vivo. In contrast, the fullerenols or doxorubicin-conjugated fullerenols exerted
      a dramatically opposite antiangiogenic activity in zebrafish and murine tumor
      angiogenesis models. Dissecting the angiogenic phenotype into discrete cellular
      steps revealed that fullerenols inhibited endothelial cell proliferation, while
      CNTs attenuated the cytotoxic effect of doxorubicin on the endothelial cells.
      Interestingly, CNT promoted endothelial tubulogenesis, a late step during
      angiogenesis. Further, mechanistic studies revealed that CNTs, but not
      fullerenols, induced integrin clustering and activated focal adhesion kinase and
      downstream phosphoinositide-3-kinase (PI3K) signaling in endothelial cells, which
      can explain the distinct angiogenic outcomes. The results of the study highlight
      the function of physical parameters of nanoparticles in determining their
      activity in biological settings.

PMID- 20043663
TI  - Structural examination of easel paintings with optical coherence tomography.
AB  - Identification of the order, thickness, composition, and possibly the origin of
      the paint layers forming the structure of a painting, that is, its stratigraphy,
      is important in confirming its attribution and history as well as planning
      conservation treatments. The most common method of examination is analysis of a
      sample collected from the art object, both visually with a microscope and
      instrumentally through a variety of sophisticated, modern analytical tools.
      Because of its invasiveness, however, sampling is less than ideally compatible
      with conservation ethics; it is severely restricted with respect to the amount of
      material extirpated from the artwork. Sampling is also rather limited in that it
      provides only very local information. There is, therefore, a great need for a
      noninvasive method with sufficient in-depth resolution for resolving the
      stratigraphy of works of art. Optical coherence tomography (OCT) is a
      noninvasive, noncontact method of optical sectioning of partially transparent
      objects, with micrometer-level axial resolution. The method utilizes near
      infrared light of low intensity (a few milliwatts) to obtain cross-sectional
      images of various objects; it has been mostly used in medical diagnostics.
      Through the serial collection of many such images, volume information may be
      extracted. The application of OCT to the examination of art objects has been in
      development since 2003. In this Account, we present a short introduction to the
      technique, briefly discuss the apparatus we use, and provide a paradigm for
      reading OCT tomograms. Unlike the majority of papers published previously, this
      Account focuses on one, very specific, use of OCT. We then consider two examples
      of successful, practical application of the technique. At the request of a
      conservation studio, the characteristics of inscriptions on two oil paintings,
      originating from the 18th and 19th centuries, were analyzed. In the first case,
      it was possible to resolve some questions concerning the history of the work.
      From an analysis of the positions of the paint layers involved in three
      inscriptions in relation to other strata of the painting, the order of events in
      its history was resolved. It was evident that the original text had been
      overpainted and that the other inscriptions were added later, thus providing
      convincing evidence as to the painting's true date of creation. In the second
      example, a painting was analyzed with the aim of confirming the possibility of
      forgery of the artist's signature, and evidence strongly supporting this
      supposition is presented. These two specific examples of successful use of the
      technique on paintings further demonstrate how OCT may be readily adaptable to
      other similar tasks, such as in the fields of forensic or materials science. In a
      synergistic approach, in which information is obtained with a variety of
      noninvasive techniques, OCT is demonstrably effective and offers great potential
      for further development.

PMID- 20043664
TI  - Electron energy transfer rate coefficients of carbon dioxide.
AB  - An extensive set of integral cross sections (ICSs) for electron impact
      vibrational excitation of the CO(2) molecule has been used to calculate electron
      energy transfer rate coefficients. The ICSs for electron impact symmetric stretch
      vibrational excitation are measured by using a high resolution double trochoidal
      electron spectrometer, while ICSs for the bending and asymmetric vibrations have
      been adopted from previous publications. Calculations of the energy transfer rate
      coefficients are performed for the equilibrium conditions in the mean electron
      energy range from 0 to 11 eV. By use of extended Monte Carlo simulations,
      electron energy distribution functions (EEDFs) and electron energy transfer rate
      coefficients are determined in the nonequilibrium conditions, for low and
      moderate values of the electric field over gas number density ratios, E/N, up to
      150 Td. Contributions of higher vibrational levels are emphasized. The results
      are compared with the data available in the literature.

PMID- 20043665
TI  - Reactions of the CN radical with benzene and toluene: product detection and low
      temperature kinetics.
AB  - Low-temperature rate coefficients are measured for the CN + benzene and CN +
      toluene reactions using the pulsed Laval nozzle expansion technique coupled with
      laser-induced fluorescence detection. The CN + benzene reaction rate coefficient
      at 105, 165, and 295 K is found to be relatively constant over this temperature
      range, (3.9-4.9) x 10(-10) cm(3) molecule(-1) s(-1). These rapid kinetics, along
      with the observed negligible temperature dependence, are consistent with a
      barrierless reaction entrance channel and reaction efficiencies approaching
      unity. The CN + toluene reaction is measured to have a rate coefficient of 1.3 x
      10(-10) cm(3) molecule(-1) s(-1) at 105 K. At room temperature, nonexponential
      decay profiles are observed for this reaction that may suggest significant back
      dissociation of intermediate complexes. In separate experiments, the products of
      these reactions are probed at room temperature using synchrotron VUV
      photoionization mass spectrometry. For CN + benzene, cyanobenzene (C(6)H(5)CN) is
      the only product recorded with no detectable evidence for a C(6)H(5) + HCN
      product channel. In the case of CN + toluene, cyanotoluene (NCC(6)H(4)CH(3))
      constitutes the only detected product. It is not possible to differentiate among
      the ortho, meta, and para isomers of cyanotoluene because of their similar
      ionization energies and the approximately 40 meV photon energy resolution of the
      experiment. There is no significant detection of benzyl radicals (C(6)H(5)CH(2))
      that would suggest a H-abstraction or a HCN elimination channel is prominent at
      these conditions. As both reactions are measured to be rapid at 105 K, appearing
      to have barrierless entrance channels, it follows that they will proceed
      efficiently at the temperatures of Saturn's moon Titan ( approximately 100 K) and
      are also likely to proceed at the temperature of interstellar clouds (10-20 K).

PMID- 20043666
TI  - Controlled synthesis of dendritic gold nanostructures assisted by supramolecular
      complexes of surfactant with cyclodextrin.
AB  - Controlled synthesis of well-defined planar Au nanodendrites with a symmetric
      single-crystalline structure consisting of trunks and side branches grown along
      the 211 directions was realized by reducing chloroauric acid in aqueous mixed
      solutions of dodecyltrimethylammonium bromide (DTAB) and beta-cyclodextrin (beta
      CD). It has been revealed that the formation of the supramolecular complexes of
      DTAB with beta-CD due to host-guest interaction is indispensable for the
      fabrication of these unique planar Au nanodendrites, and a proper CD-to-DTAB
      molar ratio is essential to their exclusive formation. A variety of Au
      nanostructures, such as branched particles consisting of rodlike branches and
      flowerlike particles consisting of platelike petals, could be readily obtained by
      simply changing the CD-to-DTAB molar ratio. Moreover, the obtained Au
      nanodendrites exhibited both a good electrocatalytic activity toward the
      oxidation of methanol and a good surface-enhanced Raman scattering (SERS)
      sensitivity for detecting p-aminothiophenol (PATP) molecules, indicating their
      potential applications including catalysis, biosensing, and nanodevices.

PMID- 20043667
TI  - Copenhagen Accord: what if it's broken?

PMID- 20043668
TI  - Successful stabilization of the elusive species {FeNO}8 in a heme model.
AB  - Nitroxyl (HNO/NO(-)) heme-adducts have been postulated as intermediates in a
      variety of catalytic processes carried out by different metalloenzymes. Hence,
      there is growing interest in obtaining and characterizing heme model nitroxyl
      complexes. The one-electron chemical reduction of the {FeNO}(7) nitrosyl
      derivative of Fe(III)(TFPPBr(8))Cl, Fe(II)(TFPPBr(8))NO (1) (TFPPBr(8) =
      2,3,7,8,12,13,17,18-octabromo-5,10,15,20-[Tetrakis-(pentafluorophenyl)]porphyrin)
      with cobaltocene yields the significantly stable {FeNO}(8) complex,
      [Co(C(5)H(5))(2)](+)[Fe(TFPPBr(8))NO](-) (2). Complex 2 was isolated and
      characterized by UV-vis, FTIR, (1)H and (15)N NMR spectroscopies. In addition,
      DFT calculations were performed to get more insight into the structure of 2.
      According to the spectroscopic and DFT results, we can state unequivocally that
      the surprisingly stable complex 2 is the elusive {FeNO}(8) species. Both
      experimental and computational data allow to assign the electronic structure of 2
      as intermediate between Fe(II)NO(-) and Fe(I)NO, which is contrasted with the
      predominant Fe(II)NO(-) character of known nonheme {FeNO}(8) complexes. The
      enhanced stability achieved for a heme model {FeNO}(8) is expected to allow
      further studies related to the reactivity of this elusive species.

PMID- 20043669
TI  - Ligand-controlled polytypism of thick-shell CdSe/CdS nanocrystals.
AB  - We report the synthesis of CdSe/CdS semiconductor core/shell nanocrystals with
      very thick (5 nm) CdS shells. As in the case of core CdSe nanocrystals, we show
      that a thick-shell CdSe/CdS core/shell structure can be synthesized in either a
      pure wurtzite (W) or a zinc-blende (ZB) crystal structure. While the growth of
      thick-shell wurtzite CdSe/CdS is quite straightforward, we observe that the
      growth of a CdS shell on zinc-blende CdSe cores is more difficult and leads to
      wurtzite/zinc-blende polytypism when primary amines are present during the shell
      formation. Using absorption spectra analysis to differentiate zinc blende from
      wurtzite CdSe, we show that primary amines can induce a nearly complete
      structural transformation of CdSe ZB cores into W cores. This better
      understanding of the CdSe ligand-dependent crystal structural evolution during
      shell growth is further used to grow large (10 nm)-diameter perfect zinc-blende
      CdSe core crystals emitting above 700 nm, and perfect ZB thick-shell CdSe/CdS
      nanocrystals. We observed that all thick-shell CdSe/CdS QDs have extremely
      reduced blinking events compared to thin-shell QDs, without any significant
      influence of crystalline structure and polytypism.

PMID- 20043670
TI  - Chemical control of the photoluminescence of CdSe quantum dot-organic complexes
      with a series of para-substituted aniline ligands.
AB  - Replacement of the native (as-synthesized) ligands of colloidal CdSe QDs with
      varying concentrations of a series of para-substituted anilines (R-An), where R
      ranges from strongly electron-withdrawing to strongly electron-donating,
      decreases the PL of the QDs. The molar ratio of R-An to QD ([R-An]:[QD]) at which
      the PL decreases by 50% shifts by 4 orders of magnitude over the series R-An. The
      model employed to describe the data combines a Freundlich binding isotherm (which
      reflects the dependence of the binding affinity of the amine headgroups of R-An
      on the substituent R) with a function that describes the response of the PL to R
      An ligands once they are bound at their equilibrium surface coverage. The latter
      function includes as a parameter the rate constant, k(nr), for nonradiative decay
      of the exciton at a site to which an R-An ligand is coordinated. The value of
      this parameter reveals that the predominant mechanism of QD-ligand interaction is
      passivation of Cd(2+) surface sites through sigma-donation for R-An ligands with
      R = H, Br, OCF(3), and reductive quenching through photoinduced hole transfer for
      R = MeO, (Me)(2)N.

PMID- 20043672
TI  - Extended O6-methylguanine methyltransferase promoter hypermethylation following n
      butylidenephthalide combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on
      inhibition of human hepatocellular carcinoma cell growth.
AB  - Epigenetic alteration of DNA methylation plays an important role in the
      regulation of gene expression associated with chemosensitivity of human
      hepatocellular (HCC) carcinoma cells. With the aim of improving the
      chemotherapeutic efficacy for HCC, the effect of the naturally occurring compound
      n-butylidenephthalide (BP), which is isolated from a chloroform extract of
      Angelica sinensis, was investigated. In both HepG2 and J5 HCC cell lines, a
      synergistic antiproliferative effect was observed when a low dosage of BP was
      combined with the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea
      (BCNU). BCNU is an alkylating agent, and it prompts us to examine one of DNA
      repair genes, O(6)-methylguanine methyltransferase (MGMT). It was evident from
      methylation-specific polymerase chain reaction (PCR) analysis that BP/BCNU
      combined treatment caused a time- and concentration-dependent enhancement of MGMT
      promoter methylation. Overexpression of MGMT could abolish BP-induced growth
      inhibition in the J5 tumor cell line as measured by colony formation assay. When
      BP was combined with BCNU and administered, it showed significant antitumor
      effects in both HepG2 and J5 xenograft tumors as compared with the use of only
      one of these drugs. The BCNU-induced apoptosis and inhibited MGMT protein
      expression in HCC cells, both in vitro and in vivo, resulting from the
      combination treatment of BP and BCNU suggest a potential clinical use of this
      compound for improving the prognosis for HCCs.

PMID- 20043671
TI  - A substructure combination strategy to create potent and selective transthyretin
      kinetic stabilizers that prevent amyloidogenesis and cytotoxicity.
AB  - Transthyretin aggregation-associated proteotoxicity appears to cause several
      human amyloid diseases. Rate-limiting tetramer dissociation and monomer
      misfolding of transthyretin (TTR) occur before its aggregation into cross-beta
      sheet amyloid fibrils. Small molecule binding to and preferential stabilization
      of the tetrameric state of TTR over the dissociative transition state raises the
      kinetic barrier for dissociation, imposing kinetic stabilization on TTR and
      preventing aggregation. This is an effective strategy to halt neurodegeneration
      associated with polyneuropathy, according to recent placebo-controlled clinical
      trial results. In three recent papers, we systematically ranked possibilities for
      the three substructures composing a typical TTR kinetic stabilizer, using fibril
      inhibition potency and plasma TTR binding selectivity data. Herein, we have
      successfully employed a substructure combination strategy to use these data to
      develop potent and selective TTR kinetic stabilizers that rescue cells from the
      cytotoxic effects of TTR amyloidogenesis. Of the 92 stilbene and dihydrostilbene
      analogues synthesized, nearly all potently inhibit TTR fibril formation.
      Seventeen of these exhibit a binding stoichiometry of >1.5 of a maximum of 2 to
      plasma TTR, while displaying minimal binding to the thyroid hormone receptor
      (<20%). Six analogues were definitively categorized as kinetic stabilizers by
      evaluating dissociation time-courses. High-resolution TTR.(kinetic stabilizer)(2)
      crystal structures (1.31-1.70 A) confirmed the anticipated binding orientation of
      the 3,5-dibromo-4-hydroxyphenyl substructure and revealed a strong preference of
      the isosteric 3,5-dibromo-4-aminophenyl substructure to bind to the inner
      thyroxine binding pocket of TTR.

PMID- 20043673
TI  - Cyclic tetrathiophenes planarized by silicon and sulfur bridges bearing
      antiaromatic cyclooctatetraene core: syntheses, structures, and properties.
AB  - Cyclic tetrathiophenes 1, 2, and 3 planarized by dimethylsilyl, sulfur, and
      sulfone bridges bearing an antiaromatic cycloocatatetraene (COT) core were
      designed and synthesized to investigate the relationship among the bent angle,
      paratropicity, and HOMO-LUMO gap of the COT ring. The bent angles of the central
      COT rings of 1-3 were theoretically estimated and experimentally determined, and
      it was found that the planarity of the COT ring was finely adjusted in the order
      of 2 > 3 > 1 by using the small differences in the bond lengths between the
      bridging units and thiophene rings. From the comparisons of NICS values and
      calculated HOMO-LUMO gaps of cyclooctatetraene at various bent angles as well as
      the optimized structures of cyclic tetrathiophenes 1-3, similar enhancement of
      the paratropicity and narrowing of the HOMO-LUMO gap with decreasing bent angle
      of the COT rings were shown in both cyclooctatetraene and cyclic tetrathiophenes
      1-3. Such predictions were experimentally proved for the first time by means of
      (1)H NMR and UV-vis measurements of 1-3. In comparison of the (1)H NMR chemical
      shifts of 1-3 with those of the corresponding precursors, upfield shifts due to a
      paratropic ring current in the COT ring were observed and the degree of shift
      increased with increasing planarity of the COT ring. Furthermore the colors of
      the solutions of 1 (lambda(max) = 483 nm), 2b (lambda(max) = 618 nm), and 3b
      (lambda(max) = 575 nm) were orange, purple, and red in CH(2)Cl(2), respectively,
      indicating that the HOMO-LUMO gaps of 1-3 become increasingly narrow with
      increasing planarity of the COT ring. Reflecting these electronic properties, CV
      measurements demonstrated the amphoteric redox properties of 1 and 2b, and the
      radical cation 1(*+), radical anion 1(*-), and dianion 1(2-) were chemically
      generated and successfully characterized by means of UV-vis, ESR, and NMR
      spectroscopies.

PMID- 20043674
TI  - Probing donor-acceptor interactions and co-conformational changes in redox active
      desymmetrized [2]catenanes.
AB  - We describe the synthesis and characterization of a series of desymmetrized donor
      acceptor [2]catenanes where different donor and acceptor units are assembled
      within a confined catenated geometry. Remarkable translational selectivity is
      maintained in all cases, including two fully desymmetrized [2]catenanes where
      both donors and acceptors are different, as revealed by X-ray crystallography in
      the solid state, and by (1)H NMR spectroscopy and electrochemistry in solution.
      In all desymmetrized [2]catenanes the co-conformation is dominated by the
      strongest donor and acceptor pairs, whose charge-transfer interactions also
      determine the visible absorption properties. Voltammetric and
      spectroelectrochemical experiments show that the catenanes can be reversibly
      switched among as many as seven states, characterized by distinct electronic and
      optical properties, by electrochemical stimulation in a relatively narrow and
      easily accessible potential window. Moreover in some of these compounds the
      oxidation of the electron donor units or the reduction of the electron acceptor
      ones causes the circumrotation of one molecular ring with respect to the other.
      These features make these compounds appealing for the development of molecular
      electronic devices and mechanical machines.

PMID- 20043675
TI  - Metabolism of (-)-epigallocatechin gallate by rat intestinal flora.
AB  - Anaerobic metabolism of (-)-epigallocatechin gallate (EGCg) by rat intestinal
      bacteria was investigated in vitro. First, intestinal bacteria which are capable
      of hydrolyzing EGCg to (-)-epigallocatechin (EGC) and gallic acid (2) were
      screened with 169 strains of enteric bacteria. As a result, Enterobacter
      aerogenes, Raoultella planticola, Klebsiella pneumoniae susp. pneumoniae, and
      Bifidobacterium longum subsp. infantis were found to hydrolyze EGCg. Subsequent
      steps of EGCg metabolism are degradation of EGC (1) by intestinal bacteria. Then,
      EGC was incubated with rat intestinal bacteria in 0.1 M phosphate buffer (pH 7.1)
      and the degradation products were analyzed with time by HPLC or LC-MS. Further,
      the products formed from EGC were isolated and identified by LC-MS and NMR
      analyses. The results revealed that EGC was converted first to 1-(3',4',5'
      trihydroxyphenyl)-3-(2'',4'',6''-trihydroxyphenyl)propan-2-ol (3) by reductive
      cleavage between 1 and 2 positions of EGC, and subsequently metabolite 3 was
      converted to 1-(3',5'-dihydroxyphenyl)-3-(2'',4'',6''-trihydroxyphenyl)propan-2
      ol (4) followed by the conversion to 5-(3,5-dihydroxyphenyl)-4-hydroxyvaleric
      acid (5) by decomposition of the phloroglucinol ring in metabolite 4. This
      degradation pathway was considered to be the major route of EGCg metabolism in
      the in vitro study, but two minor routes were also found. In addition to the in
      vitro experiments, metabolites 3, 4, 5, and 6 were detected as the metabolites
      after direct injection of EGC into rat cecum. When EGCg was administered orally
      to the rats, metabolites 4, 5, 6, 11, and 12 were found in the feces. Among the
      metabolites detected, metabolite 5 was dominant both in the cecal contents and
      feces. These findings suggested that the metabolic pathway of EGCg found in the
      in vitro study may be regarded as reflecting its metabolism in vivo.

PMID- 20043676
TI  - Synthesis of dispersible Pd@CeO(2) core-shell nanostructures by self-assembly.
AB  - A methodology is described for the preparation of Pd@CeO(2) core-shell
      nanostructures that are easily dispersible in common organic solvents. The method
      involves the synthesis of Pd nanoparticles protected by a monolayer of 11
      mercaptoundecanoic acid (MUA). The carboxylic groups on the nanoparticle surfaces
      are used to direct the self-assembly of a cerium(IV) alkoxide around the metal
      particles, followed by the controlled hydrolysis to form CeO(2). The
      characterization of the nanostructures by means of different techniques, in
      particular by electron microscopy, allowed us to demonstrate the nature of core
      shell systems, with CeO(2) nanocrystals forming a shell around the MUA-protected
      Pd core. Finally, an example of the use of these nanostructures as flexible
      precursors for the preparation of heterogeneous catalysts is reported by
      investigating the reactivity of Pd@CeO(2)/Al(2)O(3) nanocomposites toward CO
      oxidation, water-gas shift (WGS), and methanol steam reforming reactions.
      Together with CO adsorption data, these observations suggest the accessibility of
      the Pd phase in the nanocomposites.

PMID- 20043677
TI  - Effect of selective solvent addition rate on the pathways for spontaneous vesicle
      formation of ABA amphiphilic triblock copolymers.
AB  - In this study, the kinetics of vesicle formation of ABA amphiphilic triblock
      copolymers from an initially homogeneous state was theoretically and
      experimentally investigated by adding a selective solvent into the system. The
      pathway of spontaneous vesicle formation depended greatly on the selective
      solvent addition rate. At a slow addition rate, the pathway followed three
      stages: (1) the amphiphilic triblock copolymer combined into a large irregular
      aggregation; (2) the large irregular aggregation broke into big irregular
      spheres; and (3) some hydrophilic molecules in the big irregular spheres diffused
      toward the surface, and some hydrophilic molecules diffused toward the center,
      forming vesicles. However, at a fast addition rate, the pathway was as follows:
      (1) the amphiphilic triblock copolymer aggregated into many small spheres; (2)
      the small spheres merged to form rod-like micelles first and then oblate
      membranes; and (3) the oblate membranes closed up to form vesicles. This pathway
      difference for vesicle formation can be attributed to the existence of many
      metastable states in the system. This finding not only provides new insight into
      the origins of vesicles but also provides further understanding on the self
      assembly kinetics of amphiphilic block copolymers in a selective solvent.

PMID- 20043679
TI  - Budget analysis of Escherichia coli at a Southern Lake Michigan Beach.
AB  - Escherichia coli (EC) concentrations at two beaches impacted by river plume
      dynamics in southern Lake Michigan were analyzed using three-dimensional
      hydrodynamic and transport models. The relative importance of various physical
      and biological processes influencing the fate and transport of EC were examined
      via budget analysis and a first-order sensitivity analysis of model parameters.
      The along-shore advective flux of EC (CFU/m(2).s) was found to be higher compared
      to its cross-shore counterpart; however, the sum of diffusive and advective
      components was of a comparable magnitude in both directions showing the
      importance of cross-shore exchange in EC transport. Examination of individual
      terms in the EC mass balance equation showed that vertical turbulent mixing in
      the water column dominated the overall EC transport for the summer conditions
      simulated. Dilution due to advection and diffusion accounted for a large portion
      of the total EC budget in the nearshore, and the net EC loss rate within the
      water column (CFU/m(3).s) was an order of magnitude smaller compared to the
      horizontal and vertical transport rates. This result has important implications
      for modeling EC at recreational beaches; however, the assessment of the magnitude
      of EC loss rate is complicated due to the strong coupling between vertical
      exchange and depth-dependent EC loss processes such as sunlight inactivation and
      settling. Sensitivity analysis indicated that solar inactivation has the greatest
      impact on EC loss rates. Although these results are site-specific, they clearly
      bring out the relative importance of various processes involved.

PMID- 20043680
TI  - Urotensin-II receptor modulators as potential drugs.

PMID- 20043678
TI  - Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane
      (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the
      treatment of cognitive disorders in schizophrenia: synthesis, SAR development,
      and in vivo efficacy in cognition models.
AB  - A novel alpha 7 nAChR agonist, 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4
      diazabicyclo[3.2.2]nonane (24, CP-810,123), has been identified as a potential
      treatment for cognitive deficits associated with psychiatric or neurological
      conditions including schizophrenia and Alzheimer's disease. Compound 24 is a
      potent and selective compound with excellent pharmaceutical properties. In
      rodent, the compound displays high oral bioavailability and excellent brain
      penetration affording high levels of receptor occupancy and in vivo efficacy in
      auditory sensory gating and novel object recognition. The structural diversity of
      this compound and its preclinical in vitro and in vivo package support the
      hypothesis that alpha 7 nAChR agonists may have potential as a pharmacotherapy
      for the treatment of cognitive deficits in schizophrenia.

PMID- 20043681
TI  - Mechanism of heterolysis of H2 by an unsaturated d8 nickel center: via
      tetravalent nickel?
AB  - Collision of H(2) with the unusual nickel complex, (PNP)Ni(+), where PNP =
      ((t)Bu(2)PCH(2)SiMe(2))(2)N, forms a rare dihydrogen complex of the d(8)
      configuration which then rearranges to heterolytically cleave the H-H bond.
      Experimental studies support a short H/H distance in the coordinated diatomic,
      and DFT calculations show that the transition state for heterolysis, in spite of
      the fact that this involves an amide nitrogen located trans to the H(2), has the
      H/H bond fully split, and has all the geometric features of Ni(IV), but this is a
      local maximum, not a minimum.

PMID- 20043682
TI  - Proteomic analysis of human U937 cell line activation mediated by Haemophilus
      influenzae type b P2 porin and its surface-exposed loop 7.
AB  - The virulence of Haemophilus influenzae type b (Hib) has been attributed to a
      variety of potential factors associated with its cell surface, including
      lipopolysaccharides (LPS) and major outer membrane proteins (OMPs). P2 porin, one
      of the best-characterized porins in terms of its functional characteristics, is
      the most abundant OMP in Hib and has also been shown to possess proinflammatory
      activity. To characterize the role played by bacterial surface components in
      disease onset and development, the proteomic profiling of human U937 cell line
      activated by H. influenzae type b P2 porin and its most active surface-exposed
      loop (L7) was performed by means of two-dimensional electrophoresis and mass
      spectrometry. The study provided a list of candidate proteins with potential
      relevance in the host immune and inflammatory response. Most of the
      differentially expressed proteins are involved in metabolic processes,
      remodelling of cytoskeleton, stress response and signal transduction pathways.
      The results constitute the basis for dissecting signal transduction cascades
      activated by P2 stimulation and gain insights into the molecular events involved
      in the modulation of pathogen-host cell interactions.

PMID- 20043683
TI  - Resonance electron capture by serine.
AB  - Formation of negative ions via dissociative electron attachment (DEA) to the
      amino acid serine in the gas phase was studied using two different crossed
      electron/molecular beam techniques and quantum chemical calculations. Resonance
      electron capture mass spectrum and effective ion yield curves of 16 negative ions
      were measured over the electron energy range from close to 0 to 11 eV. The
      negative ions from serine were detected from resonance states in the vicinity of
      0, 1.3, 5, and 8 eV. The dominant reaction channel at low electron energies was
      (M-H)(-). The relative cross section for this ion exceeds more than 20 times that
      of any other fragment negative ions. A high-resolution experiment was applied to
      study fine structures in (M-H)(-) cross section. We have found that the second OH
      group influences some dissociative channels. Quantum chemical calculations were
      applied to interpret products of the DEA reaction channels.

PMID- 20043684
TI  - Neutral dissociation of superexcited oxygen molecules in intense laser fields.
AB  - Superexcited states (SESs) of oxygen molecules and their neutral dissociation
      processes have been studied both experimentally and theoretically using intense
      femtosecond laser. We find that at the laser intensity of approximately 2 x
      10(14) W/cm(2), ultrashort laser pulse causes neutral dissociation of oxygen
      molecule by way of SESs. The dissociation products are the excited neutral oxygen
      atoms, which are observed through fluorescence spectroscopy. Laser power
      dependence of the fluorescence intensity shows that each molecule effectively
      absorbs an average of ten laser photons. The total energy absorbed is sufficient
      to stimulate the molecule to many of the SESs. The effect is equivalent to single
      photon excitation in the extreme-ultraviolet (XUV) region by synchrotron
      radiation (SR). Morse potential energy curves (PECs) are constructed for the SESs
      of O(2) molecules. In light of the PECs, predissociation mechanism is proposed
      for the neutral dissociation. Quasi-classical trajectory (QCT) calculations show
      that the predissociation time is as short as 100 fs, which is consistent with our
      experimental measurement using ultrafast pump-probe technique.

PMID- 20043685
TI  - Platinum-assisted isomerization of 1-methylenehydrazine into 1-carbenehydrazine.
AB  - This theoretical study addresses the experimentally known fact that the ligand
      system 1-(2-(diphenylphosphino)benzylidene)-2-phenylhydrazine (L) coordinates to
      palladium centers via the N atom as a 1-methylenehydrazine ligand. In the case of
      platinum, a 1,2-H shift occurs, and a coordination via the C atom of the newly
      formed 1-carbenehydrazine ligand is observed. DFT calculations show that the free
      1-methylenehydrazine ligand is favored over the free 1-carbenehydrazine ligand by
      ca. 42 kcal mol(-1). Coordination to a metal center, however, lowers this energy
      difference to ca. 8-14 kcal mol(-1) in the case of Pd and to essentially zero for
      Pt.

PMID- 20043686
TI  - Photoinduced antiferromagnetic to ferromagnetic crossover in organic systems.
AB  - Magnetization reversal is important for different technological applications.
      Photoinduced magnetization reversal is easier to implement than conventional
      reversal methods. Here, we theoretically design and investigate the photomagnetic
      property of azobenzene based diradical systems, where trans isomers convert into
      corresponding cis forms upon irradiation with light of appropriate wavelength.
      The coupling constant values have been estimated using the broken symmetry
      approach in the density functional theory framework. In each case, the trans
      isomer is found to be antiferromagnetic, while the cis form is ferromagnetic in
      nature. Therefore, photoinduced magnetic crossover from antiferromagnetic to
      ferromagnetic regime would be observed. This is a new observation in case of the
      systems of organic origin. Importance of such systems for photomagnetic switches,
      sensors, high density data storage, spin valves, and semiconductor spintronic
      materials have also been discussed with support from density of state analysis,
      singly occupied molecular orbital-singly occupied molecular orbital energy gaps
      and spin density plots.

PMID- 20043687
TI  - Intramolecular charge transfer with fluorazene and N-phenylpyrrole.
AB  - The reaction from the initially prepared locally excited (LE) precursor to the
      intramolecular charge transfer (ICT) state of the planarized fluorazene (FPP) is
      investigated and compared with its flexible counterpart N-phenylpyrrole (PP). The
      fluorescence spectra of FPP and PP at 25 degrees C in solvents of different
      polarity reveal that the onset of a LE --> ICT reaction occurs at lower polarity
      (tetrahydrofuran, epsilon = 7.39) for FPP than for PP (1,2-dichloroethane,
      epsilon = 10.4). In accordance with this observation, the ICT reaction enthalpy 
      DeltaH is larger for FPP than for PP, 16.7 versus 6.7 kJ/mol in ethyl cyanide
      (EtCN). The larger ICT efficiency of FPP is related to the smaller energy gap
      between the two lowest excited singlet states DeltaE(S(1),S(2)): 3680 cm(-1) for
      FPP and 4070 cm(-1) for PP in n-hexane, as would be expected in the context of
      the PICT model. From picosecond fluorescence decays in EtCN at -45 degrees C it
      is found that the LE --> ICT reaction rate constant k(a) of FPP is with 9.8 x
      10(10) s(-1) considerably larger than that of PP with 3.9 x 10(10) s(-1). From
      femtosecond transient absorption spectra in acetonitrile (MeCN) at 22 degrees C,
      an ICT reaction time of 1.6 ps is obtained for FPP, shorter than the 4.0 ps
      determined for PP. The results show that a perpendicular twist of the pyrrole and
      phenyl subgroups is not required for an efficient ICT reaction with PP, the
      planarization of FPP even making this reaction faster. The similarity of the ESA
      spectra of FPP with those of PP in MeCN, with ICT absorption maxima at 365 nm
      (FPP) and 370 nm (PP), leads to the conclusion that both ICT states have a planar
      structure.

PMID- 20043688
TI  - Preparation of poly(acrylic acid) particles by dispersion polymerization in an
      ionic liquid.
AB  - Poly(acrylic acid) (PAA) particles were successfully prepared by dispersion
      polymerization of acrylic acid in ionic liquid, N,N-diethyl-N-methyl-N-(2
      methoxyethyl)ammonium bis(trifluoro-methanesulfonyl)amide ([DEME][TFSA]) at 70
      degrees C with low hydrolysis grade (35.4%) poly(vinyl alcohol) as stabilizer.
      Interestingly, the PAA particles were easily extracted as particle state with
      water. Thus, the PAA particles had a cross-linked structure during the
      polymerization without cross-linker. Moreover, it was also noted that the cross
      linking density of the PAA particles could be controlled by thermal treatment at
      various temperatures in [DEME][TFSA] utilizing the advantages of nonvolatility
      and high thermal stability of the ionic liquid.

PMID- 20043689
TI  - A DFT and ab initio benchmarking study of metal-alkane interactions and the
      activation of carbon-hydrogen bonds.
AB  - Density functional theory and ab initio methods have been used to calculate the
      structures and energies of minima and transition states for the reactions of
      methane coordinated to a transition metal. The reactions studied are reversible C
      H bond activation of the coordinated methane ligand to form a transition metal
      methyl hydride complex and dissociation of the coordinated methane ligand. The
      reaction sequence can be summarized as L(x)M(CH(3))H <==> L(x)M(CH(4)) <==> L(x)M
      + CH(4), where L(x)M is the osmium-containing fragment
      (C(5)H(5))Os(R(2)PCH(2)PR(2))(+) and R is H or CH(3). Three-center metal-carbon
      hydrogen interactions play an important role in this system. Both basis sets and
      functionals have been benchmarked in this work, including new correlation
      consistent basis sets for a third transition series element, osmium. Double zeta
      quality correlation consistent basis sets yield energies close to those from
      calculations with quadruple-zeta basis sets, with variations that are smaller
      than the differences between functionals. The energies of important species on
      the potential energy surface, calculated by using 10 DFT functionals, are
      compared both to experimental values and to CCSD(T) single point calculations.
      Kohn-Sham natural bond orbital descriptions are used to understand the
      differences between functionals. Older functionals favor electrostatic
      interactions over weak donor-acceptor interactions and, therefore, are not
      particularly well suited for describing systems--such as sigma-complexes--in
      which the latter are dominant. Newer kinetic and dispersion-corrected functionals
      such as MPW1K and M05-2X provide significantly better descriptions of the bonding
      interactions, as judged by their ability to predict energies closer to CCSD(T)
      values. Kohn-Sham and natural bond orbitals are used to differentiate between
      bonding descriptions. Our evaluations of these basis sets and DFT functionals
      lead us to recommend the use of dispersion corrected functionals in conjunction
      with double-zeta or larger basis sets with polarization functions for
      calculations involving weak interactions, such as those found in sigma-complexes
      with transition metals.

PMID- 20043690
TI  - Tetratungsten oxide clusters W4O(n)(-/0) (n = 10-13): structural evolution and
      chemical bonding.
AB  - Density functional theory (DFT) calculations are carried out to investigate the
      electronic and structural properties of a series of tetratungsten oxide clusters,
      W(4)O(n)(-/0) (n = 10-13). Generalized Koopmans' theorem is applied to predict
      the vertical detachment energies and simulate the photoelectron spectra (PES). A
      large energy gap (approximately 2.9 eV) is observed for the stoichiometric
      W(4)O(12) cluster, which reaches the bulk value. The calculations suggest that
      W(4)O(12)(-/0) have the planar eight-membered ring structures, in which each
      tungsten atom is tetrahedrally coordinated with two bridging O atoms and two
      terminal O atoms. W(4)O(10)(-/0) and W(4)O(11)(-) can be viewed as removing two
      and one terminal O atoms from W(4)O(12)(-/0), respectively. The W(4)O(11) neutral
      is an interesting species, which possesses the pentabridged structure. We show
      that W(4)O(11)(-) contains a localized W(3+) site, which can readily react with
      O(2) to form the W(4)O(13)(-) cluster, whereas the corresponding neutral
      W(4)O(13) can be viewed as replacing a terminal oxygen in W(4)O(12) by a peroxo
      O(2) unit. Molecular orbital analyses are performed to analyze the chemical
      bonding in the tetratungsten oxide clusters and to elucidate their electronic and
      structural evolution.

PMID- 20043691
TI  - Direct and simple fluorescence detection method for oxidized lipoproteins.
AB  - The quantification of low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) is currently one of the most important clinical measurements for
      characterizing metabolic syndrome. However, recent studies have revealed
      additional factors that may be more strongly associated with the coronary heart
      disease than simple measurement of LDL or HDL levels, such as small dense (sd)
      LDL particles and oxidized LDL or HDL particles. Although several methods using
      enzyme-antibody detection systems or fluorescent probes have been devised to
      characterize these factors, such methods are expensive to implement for clinical
      measurements. Here, we present a straightforward analytical method for direct
      quantitation of oxidized lipoproteins by fluorescence spectrometry, with
      excitation in the UV (365 +/- 10 nm) or visible (470 +/- 10 nm) range and
      emission detected at 450 +/- 30 nm or 535 +/- 15 nm. This method can be readily
      applied for clinical measurement in patients with dyslipidemia using only 1
      microL of 1 mg/mL of lipoprotein and without the need for any expensive detection
      antibodies. Using this new technique, biological samples from patients with
      dyslipidemia showed higher fluorescence intensities than samples from normal
      subjects when detecting oxidized LDL and light HDL (d = 1.063-1.125 g/mL),
      whereas samples from patients with dyslipidemia showed lower fluorescence
      intensities than samples from normal subjects when measuring oxidized heavy HDL
      (d = 1.125-1.210 g/mL) levels.

PMID- 20043692
TI  - Electronic structures of the CdSe/CdS core-shell nanorods.
AB  - The electronic structures of the CdSe/CdS core-shell nanorods are systemically
      investigated by large-scale first-principles quality calculations. The effects of
      band alignment, quantum confinement, piezoelectric field, and dipole moments are
      analyzed and delineated by comparing the results of systems with or without some
      of these attributes. We found complicated interplays between these effects in
      determining the nanorod band gap and electron hole wave function localizations.
      The hole wave function is found to be localized inside the CdSe core, while the
      electron wave function is localized in the CdS shell, with its distance to the
      CdSe core depending on the surface passivation. The permanent dipole moment
      induced by different surface passivations can change the electron hole
      separation, while the piezoelectric effect plays a relatively minor role.
      Finally, we demonstrate that it is straightforward to manipulate the nanorod
      electronic structure by changing its CdSe core position.

PMID- 20043693
TI  - NOR and AND logic gates based on supramolecular porphyrin-fullerene conjugates.
AB  - Supramolecular porphyrin-fullerene conjugates are employed to build NOR and AND
      logic gates. A crown ether appended zinc porphyrin and an imidazole or an alkyl
      ammonium functionalized fullerene are utilized. Quenching of zinc porphyrin
      fluorescence upon addition of binding-site-selective fullerene inputs forms the
      design basis of the NOR logic gate, while replacing the fullerene entities from
      the porphyrin-fullerene conjugate and restoring the original fluorescence by
      chemical inputs form the design basis of the AND logic gate.

PMID- 20043694
TI  - Hydrophobic peptide channels and encapsulated water wires.
AB  - Peptide nanotubes with filled and empty pores and close-packed structures are
      formed in closely related pentapeptides. Enantiomorphic sequences, Boc-(D)Pro-Aib
      Xxx-Aib-Val-OMe (Xxx = Leu, 1; Val, 2; Ala, 3; Phe, 4) and Boc-Pro-Aib-(D)Xxx-Aib
      (D)Val-OMe ((D)Xxx = (D)Leu, 5; (D)Val, 6; (D)Ala, 7; (D)Phe, 8), yield molecular
      structures with a very similar backbone conformation but varied packing patterns
      in crystals. Peptides 1, 2, 5, and 6 show tubular structures with the molecules
      self-assembling along the crystallographic six-fold axis (c-axis) and revealing a
      honeycomb arrangement laterally (ab plane). Two forms of entrapped water wires
      have been characterized in 2: 2a with d(O...O) = 2.6 A and 2b with d(O...O) = 3.5
      A. The latter is observed in 6 (6a) also. A polymorphic form of 6 (6b), grown
      from a solution of methanol-water, was observed to crystallize in a monoclinic
      system as a close-packed structure. Single-file water wire arrangements
      encapsulated inside hydrophobic channels formed by peptide nanotubes could be
      established by modeling the published structures in the cases of a cyclic peptide
      and a dipeptide. In all the entrapped water wires, each water molecule is
      involved in a hydrogen bond with a previous and succeeding water molecule. The O
      H group of the water not involved in any hydrogen bond does not seem to be
      involved in an energetically significant interaction with the nanotube interior,
      a general feature of the one-dimensional water wires encapsulated in hydrophobic
      environments. Water wires in hydrophobic channels are contrasted with the single
      file arrangements in amphipathic channels formed by aquaporins.

PMID- 20043695
TI  - High yield access to silylene RSiCl (R = PhC(NtBu)2) and its reactivity toward
      alkyne: synthesis of stable disilacyclobutene.
AB  - Two new approaches for synthesizing RSiCl, (R = PhC(NtBu)(2)) are reported by the
      reaction of RSiHCl(2) with bis-trimethyl silyl lithium amide and N-heterocyclic
      carbene respectively. In the former method silylene is produced in 90% yield. The
      silylene was treated with biphenyl alkyne to afford the disilacyclobutene system.
      This is a rare example of two five-coordinate silicon centers arranged adjacent
      to each other in a four-membered ring. Furthermore, we fluorinated the four
      membered ring by trimethyltin fluoride to obtain the fluoro substituted
      disilacyclobutene.

PMID- 20043696
TI  - Discovery of cyclic acylguanidines as highly potent and selective beta-site
      amyloid cleaving enzyme (BACE) inhibitors: Part I--inhibitor design and
      validation.
AB  - A number of novel amidine containing heterocycles were designed to reproduce the
      unique interaction pattern, revealed by X-ray crystallography, between the BACE-1
      catalytic diad and a weak NMR screening hit (3), with special attention paid to
      maintaining the appropriate basicity and limiting the number of H-bonding donors
      of these scaffolds. The iminohydantoin cores (10 and 23) were examined first and
      found to interact with the catalytic diad in one of two binding modes (A and B),
      each with the iminohydantoin core flipped 180 degrees in relation to the other.
      The amidine structural motif within each core forms a bidentate interaction with
      a different aspartic acid of the catalytic diad. Both modes reproduced a highly
      conserved interaction pattern between the inhibitors and the catalytic
      aspartates, as revealed by 3. Potent iminohydantoin BACE-1 inhibitors have been
      obtained, validating the molecular design as aspartyl protease catalytic site
      inhibitors. Brain penetrant small molecule BACE inhibitors with high ligand
      efficiencies have been discovered, enabling multiple strategies for further
      development of these inhibitors into highly potent, selective and in vivo
      efficacious BACE inhibitors.

PMID- 20043697
TI  - External and internal guest binding of a highly charged supramolecular host in
      water: deconvoluting the very different thermodynamics.
AB  - NMR, UV-vis, and isothermal titration calorimetry (ITC) measurements probe
      different aspects of competing host-guest equilibria as simple alkylammonium
      guest molecules interact with both the exterior (ion-association) and interior
      (encapsulation) of the [Ga(4)L(6)](12-) supramolecular assembly in water. Data
      obtained by each independent technique measure different components of the host
      guest equilibria and only when analyzed together does a complete picture of the
      solution thermodynamics emerge. Striking differences between the internal and
      external guest binding are found. External binding is enthalpy driven and mainly
      due to attractive interactions between the guests and the exterior surface of the
      assembly while encapsulation is entropy driven as a result of desolvation and
      release of solvent molecules from the host cavity.

PMID- 20043698
TI  - Monitoring phase behavior of sub- and supercritical CO2 confined in porous
      fractal silica with 85% porosity.
AB  - Phase behavior of CO(2) confined in porous fractal silica with volume fraction of
      SiO(2) phi(s) = 0.15 was investigated using small-angle neutron scattering (SANS)
      and ultrasmall-angle neutron scattering (USANS) techniques. The range of fluid
      densities (0 < (rho(CO(2)))(bulk) < 0.977 g/cm(3)) and temperatures (T = 22
      degrees C, 35 and 60 degrees C) corresponded to gaseous, liquid, near critical
      and supercritical conditions of the bulk fluid. The results revealed formation of
      a dense adsorbed phase in small pores with sizes D < 40 A at all temperatures. At
      low pressure (P < 55 bar, (rho(CO(2)))(bulk) < 0.2 g/cm(3)) the average fluid
      density in pores may exceed the density of bulk fluid by a factor up to 6.5 at T
      = 22 degrees C. This "enrichment factor" gradually decreases with temperature,
      however significant fluid densification in small pores still exists at
      temperature T = 60 degrees C, i.e., far above the liquid-gas critical temperature
      of bulk CO(2) (T(C) = 31.1 degrees C). Larger pores are only partially filled
      with liquid-like adsorbed layer which coexists with unadsorbed fluid in the pore
      core. With increasing pressure, all pores become uniformly filled with the fluid,
      showing no measurable enrichment or depletion of the porous matrix with CO(2).

PMID- 20043699
TI  - Total synthesis of the N,C-coupled naphthylisoquinoline alkaloids
      ancistrocladinium A and B and related analogues.
AB  - The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and
      B (4), which possess an unprecedented iminium-aryl axis and show high in vitro
      antileishmanial activities, have been synthesized via a short sequence of eight
      linear steps, without the need of protecting groups. Key steps were a Buchwald
      Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading
      to the naturally predominant M-atropo-diastereomer in the case of 3, while the
      N,C-axis is configurationally semistable in 4. The highly convergent first access
      to this type of alkaloids will now facilitate the preparation of structural
      analogues for structure-activity relationship studies. Its general applicability
      was shown by the preparation of the sterically even more congested, as yet
      unnatural N,3'- and N,1'-coupled analogues, ancistrocladinium C (5) and D (6).

PMID- 20043700
TI  - Application of fragment-based NMR screening, X-ray crystallography, structure
      based design, and focused chemical library design to identify novel microM leads
      for the development of nM BACE-1 (beta-site APP cleaving enzyme 1) inhibitors.
AB  - Fragment-based NMR screening, X-ray crystallography, structure-based design, and
      focused chemical library design were used to identify novel inhibitors for BACE
      1. A rapid optimization of an initial NMR hit was achieved by a combination of
      NMR and a functional assay, resulting in the identification of an isothiourea hit
      with a K(d) of 15 microM for BACE-1. NMR data and the crystal structure revealed
      that this hit makes H-bond interactions with the two catalytic aspartates,
      occupies the nonprime side region of the active site of BACE-1, and extends
      toward the S3 subpocket (S3sp). A focused NMR-based search for heterocyclic
      isothiourea isosteres resulted in several distinct classes of BACE-1 active site
      directed compounds with improved chemical stability and physicochemical
      properties. The strategy for optimization of the 2-aminopyridine lead series to
      potent inhibitors of BACE-1 was demonstrated. The structure-based design of a
      cyclic acylguanidine lead series and its optimization into nanomolar BACE-1
      inhibitors are the subject of the companion paper

PMID- 20043701
TI  - NIH conference on the future of telehealth: essential tools and technologies for
      clinical research and care--a summary. June 25-26, 2009 Bethesda, Maryland.
AB  - Major government efforts to widen the use of health information technology and
      speed the translation of biomedical research discoveries into clinical practice
      are converging with the rapid growth of the Internet to create unprecedented
      opportunities to use telehealth networks to broaden access to high-quality
      healthcare and expand the scope and reach of clinical and translational research.
      Recognizing the dual potential of telehealth networks to improve health outcomes
      and reduce barriers to participation in research, particularly in medically
      underserved communities, the National Center for Research Resources (NCRR), part
      of the National Institutes of Health (NIH), convened a national conference at the
      NIH on June 25-26, 2009, titled "Future of Telehealth: Essential Tools and
      Technologies for Clinical Research and Care," in collaboration with experts from
      the Health Resources and Services Administration, the Indian Health Service, the
      Department of Veterans Affairs, Internet2, and the NIH National Library of
      Medicine, National Institute of Biomedical Imaging and Bioengineering, and
      National Center for Minority Health and Health Disparities. The conference
      brought together over 400 subject matter experts from government, academia, and
      industry to discuss a wide range of issues in telehealth research and
      development. Its primary outcome is a set of short papers reporting on
      recommendations from thematic breakout sessions and some overarching
      recommendations that can, taken together, stimulate and help guide further
      research through new multi-agency, interdisciplinary collaborations.

PMID- 20043702
TI  - Innovation networks for improving access and quality across the healthcare
      ecosystem.
AB  - Partnerships between patient communities, healthcare providers, and academic
      researchers are key to stepping up the pace and public health impact of clinical
      and translational research supported by the National Institutes of Health. With
      emphasis shifting toward community engagement and faster translation of research
      advances into clinical practice, academic researchers have a vital stake in
      widening the use of health information technology systems and telehealth networks
      to support collaboration and innovation. However, limited interaction between
      academic institutions and healthcare providers hinders the ability to form and
      sustain the integrated networks that are needed to conduct meaningful community
      engaged research that improves public health outcomes. Healthcare providers,
      especially those affiliated with smaller practices, will need sustainable
      infrastructure and real incentives to utilize such networks, as well as training
      and additional resources for ongoing technical assistance.

PMID- 20043703
TI  - Telehealth tools for public health, emergency, or disaster preparedness and
      response: a summary report.
AB  - Rapid advances in telehealth development and adoption are increasing the spectrum
      of information and communication technologies that can be applied not only to
      individual patient care but more broadly to population health as well.
      Participants in this breakout session were asked to address, from their diverse
      perspectives, a series of questions relating to the current and potential uses of
      telehealth applications and networks for public health and emergency/disaster
      preparedness and response systems. Participants identified several gaps in
      current understanding and research emphasis. There is a clear need for more and
      larger outcome studies to assess the impact and cost benefit of telehealth
      applications in terms of improving public health at the population and community
      levels. In addition, more research is needed to demonstrate the ability of
      telehealth tools and technologies to facilitate and extend the reach of major
      national clinical and public health research initiatives. Perhaps most
      importantly, the National Institutes of Health should develop and/or strengthen
      strategic partnerships with other funding agencies with overlapping or
      complementary interests to accelerate interdisciplinary research in this rapidly
      evolving but relatively understudied and complex field.

PMID- 20043704
TI  - Toward the development of national telehealth services: the role of Veterans
      Health Administration and future directions for research.
AB  - The Veterans Health Administration (VHA) in the Department of Veteran Affairs
      (VA) has emerged as a national and international leader in the delivery and
      research of telehealth-based treatment. Several unique characteristics of care in
      VA settings intersect to create an ideal environment for telehealth modalities
      and research. However, the value of telehealth experience and initiatives in VA
      settings is limited if telehealth strategies cannot be widely exported to other
      public or private systems. Whereas a hierarchical organization, such as VA, can
      innovate and fund change relatively quickly based on provider and patient
      preferences and a growing knowledge base, other health provider organizations and
      third-party payers may likely require replicable scientific findings over time
      before incremental investments will be made to create infrastructure, reform
      regulatory barriers, and amend laws to accommodate expansion of telehealth
      modalities. Accordingly, large-scale scientifically rigorous telehealth research
      in VHA settings is essential not only to investigate the efficacy of existing and
      future telehealth practices in VHA, but also to hasten the development of
      telehealth infrastructure in private and other public health settings. We propose
      an expanded partnership between the VA, NIH, and other funding agencies to
      investigate creative and pragmatic uses of telehealth technology. To this end, we
      identify six specific areas of research we believe to be particularly relevant to
      the efficient development of telehealth modalities in civilian and military
      contexts outside VHA.

PMID- 20043705
TI  - A randomized controlled trial of telephone peer support's influence on
      breastfeeding duration in adolescent mothers.
AB  - PURPOSE: Adolescent mothers breastfeed less often and for a shorter duration than
      adult mothers. This randomized controlled trial was designed to evaluate the
      effect of telephone peer support on breastfeeding duration among adolescents.
      METHODS: Five adolescents who had previously breastfed were trained to provide
      peer support. Seventy-eight breastfeeding mothers were randomly assigned to an
      intervention group that received telephone calls from the peer support persons (n
      = 38) or to a control group that did not receive support (n = 40). An independent
      interviewer telephoned all new mothers weekly to document feeding patterns. Peer
      support persons, subjects, and the interviewer were all blinded to the research
      hypothesis and to group assignment. The primary outcome variable was "any
      breastfeeding" duration, i.e., the age at complete breastfeeding cessation. A
      secondary outcome variable was exclusive breastfeeding, i.e., the age at first
      introduction of any supplement. RESULTS: "Any breastfeeding" duration did not
      differ significantly between the groups (median 75 days in the intervention group
      vs. 35 days in the control group, p = 0.26). Among the 13 intervention and 11
      control mothers who were exclusively breastfeeding at the time of hospital
      discharge, the duration of exclusive breastfeeding was increased in the
      intervention group (median 35 days vs. 10 days, p = 0.004). CONCLUSIONS: This
      study did not demonstrate a significant effect of peer support on "any
      breastfeeding" duration. In contrast, exclusive breastfeeding duration appeared
      to be extended by peer support. This latter finding would benefit from
      confirmation in future studies. However, unless better methods are developed for
      retaining peers, this is likely to be a labor-intensive approach to extending
      exclusive breastfeeding duration among adolescent mothers.

PMID- 20043706
TI  - What do pregnant low-income women say about breastfeeding?
AB  - BACKGROUND: Although low socioeconomic status and African-American race have been
      shown to be risk factors for low rates of breastfeeding, maternal reasons for
      selection of infant feeding method are not well understood in these populations.
      METHODS: Healthy women > or =15 years of age receiving routine obstetrical care
      from nurses and nurse midwives at the outpatient clinic of MacDonald Women's
      Hospital, Case Medical Center, Cleveland, OH were surveyed using a questionnaire
      interview including Likert-scaled and open-ended questions. All responses to the
      six open-ended queries were transcribed. Content analysis was used to categorize
      these responses into three to seven descriptive themes for each question. The
      authors and two other clinically experienced reviewers participated in theme
      development, which involved categorization by individual reviewers and then by
      the group; a full consensus was achieved at each stage. University Hospitals
      Institutional Review Board approved the study. RESULTS: Of 186 eligible women,
      179 (96%) consented, and 176 (95%) were interviewed. Median age was 22 years
      (range, 15-41 years), 68 (41%) had greater than a high school education, 167
      (95%) were African-American, 167 (non-identical 95%) were unmarried, and 87 (49%)
      were multiparous. When interviewees were asked, "What is the biggest reason you
      want to breastfeed?," responses included maternal reasons, infant-related
      reasons, and advice of others. When women were asked, "What would stop you from
      breastfeeding?," responses included lifestyle reasons, pain-related reasons,
      lactation process issues, hypothetical medical reasons, and maternal reluctance.
      CONCLUSIONS: Expectant low-income African-American inner-city women appear well
      informed about the benefits of breastfeeding. Obstacles to breastfeeding that may
      be susceptible to intervention include fear of pain, lifestyle issues, and
      lactation process concerns. "I want to breastfeed because I don't want to get up
      in the middle of the night." "I wouldn't breastfeed if it hurt." "He [the father
      of my baby] does not want me to breastfeed because the baby might want to suck on
      his nipples."

PMID- 20043707
TI  - Comfort with the idea of formula feeding helps explain ethnic disparity in
      breastfeeding intentions among expectant first-time mothers.
AB  - OBJECTIVES: Little is known regarding modifiable factors that may explain
      sociodemographic disparities in breastfeeding rates among women in the United
      States. Using a mediation model approach, we examined the relative contributions
      of breastfeeding and formula feeding psychosocial factors in explaining
      disparities in breastfeeding intentions. METHODS: We interviewed 532 expectant
      first-time mothers regarding exposure to breastfeeding by others (breastfeeding
      exposure), comfort with ideas of breastfeeding (breastfeeding comfort) and
      formula feeding (formula feeding comfort), and breastfeeding self-efficacy. We
      used logistic regression to evaluate the independent and mediating effects of
      these variables on strength of intention to fully breastfeed for 6 months
      (breastfeeding intention). RESULTS: The ethnic distribution of the sample was 41%
      white, non-Hispanic; 27% Hispanic; 14% African-American; 12% Asian; and 6% mixed
      or other ethnicity. In the overall sample, formula feeding comfort, breastfeeding
      comfort, and breastfeeding self-efficacy all independently predicted
      breastfeeding intention (p < 0.0001), but formula feeding comfort had the largest
      effect: adjusted odds of stronger breastfeeding intention increased threefold for
      each 1-level decrease (among four levels) in formula feeding comfort. The
      unadjusted odds (95% confidence interval) of stronger breastfeeding intention
      were 0.37 (0.24-0.58) for African-American versus non-African-American women;
      African-American women had higher formula feeding comfort (2.08 [1.32-3.29]) but
      similar breastfeeding comfort, breastfeeding self-efficacy, and breastfeeding
      exposure. Formula feeding comfort mediated 37% of the disparity in breastfeeding
      intentions between African-American and non-African-American women. CONCLUSIONS:
      Formula feeding comfort strongly predicted and substantially mediated ethnic
      disparity in breastfeeding intention. These results suggest that research and
      public health efforts aimed at increasing exclusive breastfeeding rates should
      include consideration of formula feeding attitudes.

PMID- 20043708
TI  - Breastfeeding advocacy day, June 10, 2009, Washington, DC.

PMID- 20043709
TI  - Palliative medicine: politics and policy.

PMID- 20043710
TI  - Xenogeneic liver models for gene therapy.

PMID- 20043711
TI  - Developing next-generation telehealth tools and technologies: patients, systems,
      and data perspectives.
AB  - The major goals of telemedicine today are to develop next-generation telehealth
      tools and technologies to enhance healthcare delivery to medically underserved
      populations using telecommunication technology, to increase access to medical
      specialty services while decreasing healthcare costs, and to provide training of
      healthcare providers, clinical trainees, and students in health-related fields.
      Key drivers for these tools and technologies are the need and interest to
      collaborate among telehealth stakeholders, including patients, patient
      communities, research funders, researchers, healthcare services providers,
      professional societies, industry, healthcare management/economists, and
      healthcare policy makers. In the development, marketing, adoption, and
      implementation of these tools and technologies, communication, training, cultural
      sensitivity, and end-user customization are critical pieces to the process. Next
      generation tools and technologies are vehicles toward personalized medicine,
      extending the telemedicine model to include cell phones and Internet-based
      telecommunications tools for remote and home health management with video
      assessment, remote bedside monitoring, and patient-specific care tools with event
      logs, patient electronic profile, and physician note-writing capability.
      Telehealth is ultimately a system of systems in scale and complexity. To cover
      the full spectrum of dynamic and evolving needs of end-users, we must appreciate
      system complexity as telehealth moves toward increasing functionality,
      integration, interoperability, outreach, and quality of service. Toward that end,
      our group addressed three overarching questions: (1) What are the high-impact
      topics? (2) What are the barriers to progress? and (3) What roles can the
      National Institutes of Health and its various institutes and centers play in
      fostering the future development of telehealth?

PMID- 20043712
TI  - Utah Population Database: a tool to study the hereditary element of nonsyndromic
      neurosurgical diseases.
AB  - Understanding the genetic alterations that contribute to the development of
      different disease states is key to the ability to screen and treat patients
      afflicted with these diseases and may someday enable us to prevent their
      development. The high degree of morbidity and mortality associated with
      neurosurgical diseases makes this understanding particularly important.
      Mechanisms for early diagnosis, followed by appropriate treatment in these
      patients, could significantly alter the morbidity and mortality rates in patients
      with neurosurgical diseases. The Utah Population Database (UPDB) is a unique
      resource that allows population-based analysis of the familial nature of diseases
      with the identification of high-risk pedigrees and predisposition genes. The UPDB
      was initially used to study the hereditary element of cancer, but its application
      is now expanding to include the neurogenomics of neurosurgical diseases.
      Specifically, the familial and genetic contribution to intracranial aneurysms and
      nonsyndromic intracranial malignant diseases has been reported in the literature.
      The UPDB identifies the familial contribution by examining genealogical records
      that have been linked with clinical, demographic, and diagnostic data compiled in
      state records. From this information, one can identify possible genetic targets
      for future therapies.

PMID- 20043713
TI  - Introduction: neurogenomics and neuroproteomics.

PMID- 20043715
TI  - Is an endothelial nitric oxide synthase gene mutation a risk factor in the origin
      of intraventricular hemorrhage?
AB  - OBJECT: Studies have shown decreased levels of nitric oxide (NO), the product of
      endothelial NO synthase (eNOS) gene activity, in infants with respiratory
      conditions and intraventricular hemorrhage (IVH). The authors evaluated the
      association of the eNOS gene promoter polymorphism T-786C with the cause of these
      conditions (respiratory conditions and IVH) in premature infants. METHODS: Blood
      samples from 124 African American premature infants were studied. The DNA was
      isolated and microplate polymerase chain reaction-restriction fragment length
      polymorphism assay was performed. Genotypes were scored as: TT homozygotes with
      140 bp and 40 bp; CC homozygotes with 90 bp, 50 bp, and 40 bp; and TC
      heterozygotes with 140 bp, 90 bp, 50 bp, and 40 bp. Genotypes were stratified
      according to ethnicity, preterm status, and prematurity conditions. RESULTS: The
      mutant allele -786C was present in 15.3% of premature infants with respiratory
      distress syndrome, bronchopulmonary dysplasia, and IVH, compared with 7.25% in
      those premature infants without these conditions. A significant 2-fold increase
      of the mutant allele in patients compared with controls (p = 0.04, OR 2.3)
      reveals that the eNOS -786C allele could be a significant risk factor in the
      origin of respiratory conditions and IVH in premature infants. CONCLUSIONS: These
      results suggest that the mutant eNOS -786C allele is a significant risk factor in
      the origin of respiratory and IVH diseases, probably mediating an insufficient
      supply of endogenous NO in premature infants.

PMID- 20043716
TI  - Using ex vivo proton magnetic resonance spectroscopy to reveal associations
      between biochemical and biological features of meningiomas.
AB  - OBJECT: The goal in this study was to determine if proton ((1)H) MR spectroscopy
      can differentiate meningioma grade and is associated with interpretations of
      biological behavior; the study was performed using ex vivo high-resolution
      spectra indicating metabolic characteristics. METHODS: Sixty-eight resected
      tissue samples of meningiomas were examined using ex vivo (1)H MR spectroscopy.
      Of these meningiomas, 46 were WHO Grade I, 14 were WHO Grade II, and 8 were WHO
      Grade III. Fifty-nine were primary meningiomas and 9 were recurrences. Invasion
      of adjacent tissue (dura mater, bone, venous sinus, brain) was found in 32 cases.
      Thirty-nine meningiomas did not rapidly recur (as defined by expansion on MR
      imaging within a 5-year follow-up period), whereas rapid recurrence was confirmed
      in 24 meningiomas, and follow-up status was unknown in 5 cases. RESULTS: The
      absolute concentrations of total alanine and creatine were decreased in high
      grade compared with low-grade meningiomas, as was the ratio of glycine to alanine
      (all p < 0.05). Additionally, alanine and the glycine/alanine ratio distinguished
      between primary and recurrent meningiomas (all p < 0.05). Finally, the absolute
      concentrations of alanine and creatine, and the glycine/alanine and
      choline/glutamate ratios were associated with rapid recurrence (p < 0.05).
      CONCLUSIONS: These data indicate that meningioma tissue can be characterized by
      metabolic parameters that are not typically identified by histopathological
      analysis alone. Creatine, glycine, and alanine may be used as markers of
      meningioma grade, recurrence, and the likelihood of rapid recurrence. These data
      validate a previous study of a separate group of Grade I meningiomas.

PMID- 20043714
TI  - Elucidating novel mechanisms of brain injury following subarachnoid hemorrhage:
      an emerging role for neuroproteomics.
AB  - Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated
      with significant patient morbidity and death. Since the first demonstration of
      cerebral vasospasm nearly 60 years ago, the preponderance of research has focused
      on strategies to limit arterial narrowing and delayed cerebral ischemia following
      SAH. However, recent clinical and preclinical data indicate a functional
      dissociation between cerebral vasospasm and neurological outcome, signaling the
      need for a paradigm shift in the study of brain injury following SAH. Early brain
      injury may contribute to poor outcome and early death following SAH. However,
      elucidation of the complex cellular mechanisms underlying early brain injury
      remains a major challenge. The advent of modern neuroproteomics has rapidly
      advanced scientific discovery by allowing proteome-wide screening in an
      objective, nonbiased manner, providing novel mechanisms of brain physiology and
      injury. In the context of neurosurgery, proteomic analysis of patient-derived CSF
      will permit the identification of biomarkers and/or novel drug targets that may
      not be intuitively linked with any particular disease. In the present report, the
      authors discuss the utility of neuroproteomics with a focus on the roles for this
      technology in understanding SAH. The authors also provide data from our
      laboratory that identifies high-mobility group box protein-1 as a potential
      biomarker of neurological outcome following SAH in humans.

PMID- 20043717
TI  - Genome-wide association studies: a powerful tool for neurogenomics.
AB  - As their power and utility increase, genome-wide association (GWA) studies are
      poised to become an important element of the neurosurgeon's toolkit for
      diagnosing and treating disease. In this paper, the authors review recent
      findings and discuss issues associated with gathering and analyzing GWA data for
      the study of neurological diseases and disorders, including those of
      neurosurgical importance. Their goal is to provide neurosurgeons and other
      clinicians with a better understanding of the practical and theoretical issues
      associated with this line of research. A modern GWA study involves testing
      hundreds of thousands of genetic markers across an entire genome, often in
      thousands of individuals, for any significant association with a particular
      disease. The number of markers assayed in a study presents several practical and
      theoretical issues that must be considered when planning the study. Genome-wide
      association studies show great promise in our understanding of the genes
      underlying common neurological diseases and disorders, as well as in leading to a
      new generation of genetic tests for clinicians.

PMID- 20043718
TI  - The many roles of microRNAs in brain tumor biology.
AB  - MicroRNAs (miRNAs) are now recognized as the primary RNAs involved in the
      purposeful silencing of the cell's own message. In addition to the established
      role of miRNAs as developmental regulators of normal cellular function, they have
      recently been shown to be important players in pathological states such as
      cancer. The authors review the literature on the role of miRNAs in the formation
      and propagation of gliomas and medulloblastomas, highlighting the potential of
      these molecules and their inhibitors as therapeutics.

PMID- 20043719
TI  - Functional genomic analysis of glioblastoma multiforme through short interfering
      RNA screening: a paradigm for therapeutic development.
AB  - Glioblastoma multiforme (GBM) is a high-grade brain malignancy arising from
      astrocytes. Despite aggressive surgical approaches, optimized radiation therapy
      regimens, and the application of cytotoxic chemotherapies, the median survival of
      patients with GBM from time of diagnosis remains less than 15 months, having
      changed little in decades. Approaches that target genes and biological pathways
      responsible for tumorigenesis or potentiate the activity of current therapeutic
      modalities could improve treatment efficacy. In this regard, several genomic and
      proteomic strategies promise to impact significantly on the drug discovery
      process. High-throughput genome-wide screening with short interfering RNA (siRNA)
      is one strategy for systematically exploring possible therapeutically relevant
      targets in GBM. Statistical methods and protein-protein interaction network
      databases can also be applied to the screening data to explore the genes and
      pathways that underlie the pathological basis and development of GBM. In this
      study, we highlight several genome-wide siRNA screens and implement these
      experimental concepts in the T98G GBM cell line to uncover the genes and pathways
      that regulate GBM cell death and survival. These studies will ultimately
      influence the development of a new avenue of neurosurgical therapy by placing the
      drug discovery process in the context of the entire biological system.

PMID- 20043720
TI  - Functional genomics to explore cancer cell vulnerabilities.
AB  - Our understanding of glioblastoma multiforme (GBM), the most common form of
      primary brain cancer, has been significantly advanced by recent efforts to
      characterize the cancer genome using unbiased high-throughput sequencing
      analyses. While these studies have documented hundreds of mutations, gene copy
      alterations, and chromosomal abnormalities, only a subset of these alterations
      are likely to impact tumor initiation or maintenance. Furthermore, genes that are
      not altered at the genomic level may play essential roles in tumor initiation and
      maintenance. Identification of these genes is critical for therapeutic
      development and investigative methodologies that afford insight into biological
      function. This requirement has largely been fulfilled with the emergence of RNA
      interference (RNAi) and high-throughput screening technology. In this article,
      the authors discuss the application of genome-wide, high-throughput RNAi-based
      genetic screening as a powerful tool for the rapid and cost-effective
      identification of genes essential for cancer proliferation and survival. They
      describe how these technologies have been used to identify genes that are
      themselves selectively lethal to cancer cells, or synthetically lethal with other
      oncogenic mutations. The article is intended to provide a platform for how RNAi
      libraries might contribute to uncovering glioma cell vulnerabilities and provide
      information that is highly complementary to the structural characterization of
      the glioblastoma genome. The authors emphasize that unbiased, systems-level
      structural and functional genetic approaches are complementary efforts that
      should facilitate the identification of genes involved in the pathogenesis of GBM
      and permit the identification of novel drug targets.

PMID- 20043721
TI  - Genomics of medulloblastoma: from Giemsa-banding to next-generation sequencing in
      20 years.
AB  - Advances in the field of genomics have recently enabled the unprecedented
      characterization of the cancer genome, providing novel insight into the molecular
      mechanisms underlying malignancies in humans. The application of high-resolution
      microarray platforms to the study of medulloblastoma has revealed new oncogenes
      and tumor suppressors and has implicated changes in DNA copy number, gene
      expression, and methylation state in its etiology. Additionally, the integration
      of medulloblastoma genomics with patient clinical data has confirmed molecular
      markers of prognostic significance and highlighted the potential utility of
      molecular disease stratification. The advent of next-generation sequencing
      technologies promises to greatly transform our understanding of medulloblastoma
      pathogenesis in the next few years, permitting comprehensive analyses of all
      aspects of the genome and increasing the likelihood that genomic medicine will
      become part of the routine diagnosis and treatment of medulloblastoma.

PMID- 20043722
TI  - Genetic basis of Parkinson disease.
AB  - Over the past few years, considerable progress has been made in understanding the
      molecular mechanisms of Parkinson disease (PD). Mutations in certain genes are
      found to cause monogenic forms of the disorder, with autosomal dominant or
      autosomal recessive inheritance. These genes include alpha-synuclein, parkin,
      PINK1, DJ-1, LRRK2, and ATP13A2. The monogenic variants are important tools in
      identifying cellular pathways that shed light on the pathogenesis of this
      disease. Certain common genetic variants are also likely to modulate the risk of
      PD. International collaborative studies and meta-analyses have identified common
      variants as genetic susceptibility risk/protective factors for sporadic PD.

PMID- 20043723
TI  - Neurofibromatosis Type 1 and tumorigenesis: molecular mechanisms and therapeutic
      implications.
AB  - Neurofibromatosis Type 1 (NF1) is a common autosomal dominant disease
      characterized by complex and multicellular neurofibroma tumors, and less
      frequently by malignant peripheral nerve sheath tumors (MPNSTs) and optic nerve
      gliomas. Significant advances have been made in elucidating the cellular,
      genetic, and molecular biology involved in tumor formation in NF1.
      Neurofibromatosis Type 1 is caused by germline mutations of the NF1 tumor
      suppressor gene, which generally result in decreased intracellular neurofibromin
      protein levels, leading to increased cascade Ras signaling to its downstream
      effectors. Multiple key pathways are involved with the development of tumors in
      NF1, including Ras/mitogen-activated protein kinase (MAPK) and Akt/mammalian
      target of rapamycin (mTOR). Interestingly, recent studies demonstrate that
      multiple other developmental syndromes (in addition to NF1) share phenotypic
      features resulting from germline mutations in genes responsible for components of
      the Ras/MAPK pathway. In general, a somatic loss of the second NF1 allele, also
      referred to as loss of heterozygosity, in the progenitor cell, either the Schwann
      cell or its precursor, combined with haploinsufficiency in multiple supporting
      cells is required for tumor formation. Importantly, a complex series of
      interactions with these other cell types in neurofibroma tumorigenesis is
      mediated by abnormal expression of growth factors and their receptors and
      modification of gene expression, a key example of which is the process of
      recruitment and involvement of the NF1(+/-) heterozygous mast cell. In general,
      for malignant transformation to occur, there must be accumulation of additional
      mutations of multiple genes including INK4A/ARF and P53, with resulting
      abnormalities of their respective signal cascades. Further, abnormalities of the
      NF1 gene and molecular cascade described above have been implicated in the
      tumorigenesis of NF1 and some sporadically occurring gliomas, and thus, these
      treatment options may have wider applicability. Finally, increased knowledge of
      molecular and cellular mechanisms involved with NF1 tumorigenesis has led to
      multiple preclinical and clinical studies of targeted therapy, including the mTOR
      inhibitor rapamycin, which is demonstrating promising preclinical results for
      treatment of MPNSTs and gliomas.

PMID- 20043724
TI  - Genetic association studies in patients with traumatic brain injury.
AB  - Traumatic brain injury (TBI) constitutes a major cause of mortality and
      disability worldwide, especially among young individuals. It is estimated that
      despite all the recent advances in the management of TBI, approximately half of
      the patients suffering head injuries still have unfavorable outcomes, which
      represents a substantial health care, social, and economic burden to societies.
      Considerable variability exists in the clinical outcome after TBI, which is only
      partially explained by known factors. Accumulating evidence has implicated
      various genetic elements in the pathophysiology of brain trauma. The extent of
      brain injury after TBI seems to be modulated to some degree by genetic variants.
      The authors' current review focuses on the up-to-date state of knowledge
      regarding genetic association studies in patients sustaining TBI, with particular
      emphasis on the mechanisms underlying the implication of genes in the
      pathophysiology of TBI.

PMID- 20043725
TI  - Survival after cerebral herniation.

PMID- 20043726
TI  - Venous anomaly.

PMID- 20043727
TI  - Traumatic brain injury outcome.

PMID- 20043728
TI  - Multidrug-resistant Acinetobacter baumannii brain abscess.

PMID- 20043729
TI  - History of detachable coils: the backdrop.

PMID- 20043730
TI  - Antisiphon device.

PMID- 20043731
TI  - Prevention of ventricular catheter obstruction and slit ventricle syndrome by the
      prophylactic use of the Integra antisiphon device in shunt therapy for pediatric
      hypertensive hydrocephalus: a 25-year follow-up study.
AB  - OBJECT: This 25-year follow-up study was performed on 120 children with
      hypertensive hydrocephalus to evaluate the influence of the early prophylactic
      implantation of the Integra antisiphon device (ASD, Integra Neurosciences Ltd.)
      on the rate of proximal shunt obstructions and the frequency of symptomatic slit
      ventricle syndrome (SVS). The adaptability of the ASD to growth, proper
      positioning of the ASD as a necessity for its successful performance, and the 3
      phases of SVS development are discussed. METHOD: Since 1978, the ASD has
      consistently been implanted either at the time of primary shunt insertion (66
      neonates, mean follow-up 11 years) or during revisions of preexisting shunts (54
      children, mean follow-up 11.8 years). The complication rate among the 54 children
      before ASD implantation (mean follow-up 8.3 years) was compared with that among
      all 120 patients once an ASD had been inserted. Shunt complications were
      documented as ventricular catheter, distal catheter, and infectious
      complications. RESULTS: The study revealed a significant long-term reduction in
      ventricular catheter obstructions and hospitalizations due to intermittent
      intracranial hypertension symptoms (symptomatic SVS) after both primary and
      secondary ASD implantation. Data in the study suggest that the high rate of
      ventricular catheter obstruction in pediatric shunt therapy is caused by
      hydrostatic suction induced by differential-pressure valve shunts during
      mobilization of the patient and that the development of a SVS can be traced back
      to this constant suction, which causes chronic CSF overdrainage and ventricular
      noncompliance. Recurrent ventricular catheter obstruction and SVS can be
      prevented by prophylactic supplementation of every shunt system with an ASD.
      CONCLUSIONS: To inhibit chronic hydrostatic suction, to prevent overdrainage and
      proximal shunt obstruction, and to avoid SVS and thus improve the patient's
      quality of life, the prophylactic implantation of an ASD in every pediatric
      hydrocephalus shunt is recommended.

PMID- 20043732
TI  - Hyperemic hydrocephalus.

PMID- 20043733
TI  - Hyperemic hydrocephalus: a new form of childhood hydrocephalus analogous to
      hyperemic intracranial hypertension in adults.
AB  - OBJECT: In the majority of adults with idiopathic intracranial hypertension
      (IIH), there is an elevation in venous pressure associated with a venous outflow
      stenosis. In about 15% of IIH patients the elevated venous pressure is associated
      with an elevation in blood flow but little or no evidence of a stenosis.
      Venostenotic IIH and idiopathic hydrocephalus in children with a normal blood
      inflow have been shown to be equivalent. The aim of this study was to test
      whether children with hydrocephalus and an elevated arterial inflow have a
      vascular pathophysiology that is analogous to the hyperemic form of IIH in
      adults. METHODS: Nine children with idiopathic hydrocephalus underwent MR imaging
      with flow quantification and were found to have arterial inflows 2 SDs above the
      mean for normal controls. Measurements of the head circumference, ventricular
      enlargement, total blood inflow, superior sagittal sinus (SSS)/straight sinus
      (SS) outflow, and the degree of collateral venous flow were performed. The
      results were compared with findings in 14 age-matched controls. RESULTS: In
      hyperemic hydrocephalus the cerebral blood inflow was elevated but the SSS and SS
      outflows were in the normal range. The sinus outflow as a percentage of the
      inflow was reduced by 8 percentage points in the SSS territory and 5 percentage
      points in the SS territory compared with findings in the controls (p = 0.04, p =
      0.003, respectively), suggesting blood was returning via collateral channels.
      CONCLUSIONS: Similar to patients with hyperemic IIH, children with hyperemic
      hydrocephalus show a significant elevation in collateral venous flow, indicating
      that the same venous pathophysiology may be operating in both conditions.

PMID- 20043734
TI  - Craniopharyngioma.

PMID- 20043735
TI  - Efficacy and safety of radical resection of primary and recurrent
      craniopharyngiomas in 86 children.
AB  - OBJECT: Optimal treatment of primary and recurrent craniopharyngiomas remains
      controversial. Radical resection and limited resection plus radiation therapy
      yield similar rates of disease control and overall survival. The data are much
      less clear for recurrent tumors. The authors report their experience with radical
      resection of both primary and recurrent craniopharyngiomas in children and
      compare the outcomes between the 2 groups. METHODS: A retrospective analysis was
      performed in 86 children younger than 21 years of age who underwent a total of
      103 operations for craniopharyngioma between 1986 and 2008; these were performed
      by the senior author. The goal was resection with curative intent in all
      patients. Two patients were lost to follow-up and were excluded from analysis.
      The mean age at the time of surgery was 9.6 years, and the mean follow-up was 9.0
      years. RESULTS: All 57 children with primary tumors underwent gross-total
      resection (GTR). A GTR was achieved in significantly fewer children with
      recurrent tumors (18 [62%] of 29). There were 3 perioperative deaths (3%). Tumor
      recurred after GTR in 14 (20%) of 71 patients. Overall survival and progression
      free survival were significantly better in patients with primary tumors at time
      of presentation to the authors' institution. There were no significant
      differences in the neurological, endocrinological, visual, or functional outcomes
      between patients with primary and those with recurrent tumors. Factors negatively
      affecting overall survival and progression-free survival include subtotal
      resection (recurrent tumors only), tumor size >or= 5 cm, or presence of
      hydrocephalus or a ventriculoperitoneal shunt. Prior radiation therapy and
      increasing tumor size were both risk factors for incomplete resection at
      reoperation. CONCLUSIONS: In the hands of surgeons with experience with
      craniopharyngiomas, the authors believe that radical resection at presentation
      offers the best chance of disease control and potential cure with acceptable
      morbidity. While GTR does not preclude recurrence and is more difficult to
      achieve in recurrent tumors, especially large and previously irradiated tumors,
      radical resection is still possible in patients with recurrent craniopharyngiomas
      with morbidity similar to that of primary tumors.

PMID- 20043736
TI  - The transsphenoidal resection of pediatric craniopharyngiomas: a case series.
AB  - OBJECT: The majority of pediatric craniopharyngiomas are treated using a
      transcranial approach. Although there is an increasing acceptance of
      transsphenoidal resection in adults, there are few reports describing this
      approach in the pediatric population. The purpose of this study is to report the
      outcomes after transsphenoidal surgery in a consecutive series of pediatric
      patients with craniopharyngiomas treated at a single institution with the goal of
      gross-total resection (GTR). METHODS: Twenty-three patients with pathologically
      proven craniopharyngiomas were identified who were 18 years of age or less at the
      time of surgery. The medical records and imaging studies of the patients were
      retrospectively reviewed. One patient who was lost to follow-up after surgery was
      excluded. RESULTS: Among the 22 patients included in the study, 11 underwent
      transsphenoidal surgery as the primary procedure and 11 underwent transsphenoidal
      surgery as a secondary procedure after a previous procedure. All patients had at
      least some sellar component to their tumor and all had either anterior or
      posterior pituitary dysfunction at presentation. In the entire cohort, a GTR was
      achieved in 15 (68%) of 22 patients, a radical subtotal resection in 4 (18%) of
      22 patients, a subtotal resection in 1 patient, and a partial resection in 2
      patients. The degree of resection was higher in the primary transsphenoidal
      group. After a mean follow-up of 82 months, 4 patients (18%) experienced
      recurrence. Recurrence occurred in 13% after GTR compared with 28.5% after all
      other degrees of resection. Tumor recurred in 9% of the primary transsphenoidal
      group and in 30% of patients who had undergone other therapies prior to the
      transsphenoidal operation. No patient who had panhypopituitarism experienced a
      gain of function postoperatively, 67% developed new panhypopituitarism, and 56%
      experienced new diabetes insipidus. Vision improved or normalized in 9 (64%) of
      14 patients presenting with visual loss. Complications included 1 death 3 weeks
      postoperatively, 2 CSF leaks, and new obesity in 37%. CONCLUSIONS:
      Transsphenoidal resection of pediatric craniopharyngiomas results in a high rate
      of both visual improvement and GTR with a low associated risk of recurrence. The
      transsphenoidal approach should be considered in selected pediatric patients with
      craniopharyngioma, especially those with infradiaphragmatic origin.

PMID- 20043737
TI  - Subarachnoid dissemination of intraventricular tumors following simultaneous
      endoscopic biopsy and third ventriculostomy.
AB  - OBJECT: Endoscopic biopsy with concomitant third ventriculostomy (ETV) is a well
      established diagnostic and therapeutic maneuver in patients presenting with
      noncommunicating hydrocephalus resulting from a tumor of the pineal region or
      posterior third ventricle. Fenestration of the floor of the third ventricle
      theoretically provides a conduit for the subarachnoid dissemination of an
      intraventricular tumor. The aim of this study was to ascertain the rate of
      leptomeningeal dissemination following this surgical procedure. METHODS: The
      authors conducted a review of all patients for whom an ETV and simultaneous
      endoscopic biopsy procedure or tumor resection had been performed at their
      institutions between 1995 and 2008. Patients were divided into high or low risk
      groups by leptomeningeal metastatic potential based on pathology. All available
      postoperative clinical and radiographic data, including MR imaging of the brain
      and spinal cord, as well as CSF sampling were evaluated when available. A review
      of the literature was then conducted to establish rates of distant leptomeningeal
      dissemination for comparative purposes. RESULTS: Thirty-two patients satisfied
      the criteria for study inclusion. Pathology revealed that 22 had a high risk for
      leptomeningeal dissemination. New leptomeningeal disease (1 yolk sac tumor and 1
      pineoblastoma) occurred in 2 patients. The median clinical and brain MR imaging
      follow-ups overall were 34 (range 2-103 months) and 38 months (range 1-94
      months), respectively. Follow-up MR imaging of the spine was performed in 12
      patients (median 7 months postoperation), and CSF was analyzed in 15 patients
      (median 1 month postoperation). A Kaplan-Meier survival analysis predicted a 2
      year metastasis-free survival of 94.7% for high-risk patients. Baseline rates of
      dissemination when ETV was not performed were in general between 8 and 24% for
      various high-risk pathologies according to a literature review. CONCLUSIONS: The
      rate of leptomeningeal metastasis of tumors in this biopsy and ETV study was not
      increased when compared with rates from large series in the literature.

PMID- 20043738
TI  - Endoscopic third ventriculostomy: outcome analysis in 368 procedures.
AB  - OBJECT: Although endoscopic third ventriculostomy (ETV) has been accepted as a
      procedure of choice for the treatment of obstructive hydrocephalus, the outcome
      of this treatment remains controversial with regard to age, cause, and long-term
      follow-up results. The goal of this study was to assess the risk of failure
      associated with these factors in a retrospective cohort study. METHODS: Between
      1999 and 2007, 368 ETVs were performed in 350 patients (165 patients < 18 years
      of age) with hydrocephalus at the University Hospital of Toulouse. Failure of ETV
      was defined as cases requiring any subsequent surgical procedure for CSF
      diversion or death related to hydrocephalus management. RESULTS: Tumors (53%),
      primary aqueductal stenosis (18%), and intracranial hemorrhage (13%) were the
      most common causes of hydrocephalus. The median follow-up period was 47 months
      (range 6-106 months), and the overall success rate was 68.5% (252 of the 368
      procedures). Patients < 6 months of age had a 5-fold increased risk of ETV
      failure than older patients (adjusted hazard ratio [HRa] 5.0; 95% CI 2.4-10.4; p
      < 0.001). Hemorrhage-related (HRa 4.0; 95% CI 1.9-8.5; p < 0.001) and idiopathic
      chronic hydrocephalus (HRa 6.3, 95% CI 2.5-15.0, p < 0.001) had a higher risk of
      failure than other causes. Most failures (97%) occurred within 2 months of the
      initial procedure. The overall morbidity rate was 10%, although most
      complications were minor. Finally, the introduction of ETV in the authors'
      department reduced the number of shunt insertions and hospital admissions for
      shunt failures by half and was a source of cost savings. CONCLUSIONS: Endoscopic
      third ventriculostomy is a safe procedure and an effective treatment option for
      hydrocephalus. Factors indicating potential poor ETV outcome seem to be very
      young children and hemorrhage-related and chronic hydrocephalus in adults.

PMID- 20043739
TI  - Surgical treatment of a clival-C2 atypical teratoid/rhabdoid tumor.
AB  - The authors present the case of en bloc resection of a clival-C2 atypical
      teratoid/rhabdoid tumor. These aggressive lesions of early childhood generally
      occur in the cerebellum or cerebral hemispheres. This 7-year-old boy presented
      with pain on turning his head and was found to have a clival-C2 mass. A
      metastatic workup was negative for disseminated disease. A transoral biopsy
      procedure revealed an atypical teratoid/rhabdoid tumor on histological
      examination. The tumor was resected via a transoral approach, and the patient's
      spine was stabilized with posterior instrumented fusion from the occiput to C-5.
      Postoperatively, the patient underwent 16 months of chemotherapy along with 6
      weeks of overlapping radiation therapy. Twenty-seven months after the initial
      surgery he presented with leg pain and was found to have a solitary metastatic
      lesion at the conus medullaris. There was no local recurrence at the clivus. The
      conus tumor was resected and found to be consistent with the primary tumor.
      Several months later the patient presented with disseminated intrathecal disease
      and ultimately died 42 months after the initial resection.

PMID- 20043740
TI  - Anterior encephaloceles in children of Assamese tea workers.
AB  - OBJECT: Anterior encephaloceles are rare congenital malformations. Most of the
      cases in the literature are reported from Southeast Asia. In India it is seen
      more frequently among manual laborers in the tea gardens of Assam. A brief
      background of the patients, clinical presentation, operative treatment, and
      outcome are discussed, with a review of the relevant literature. The causes and
      pathogenesis of anterior encephaloceles are discussed. The authors' surgical
      approach to repair of the defect, postoperative complications, and results are
      described. METHODS: Twenty-eight patients (mean age 38 months, range 1 month-12
      years) with anterior encephaloceles who presented between 1998 and 2007 are
      included in the study. Patients were assessed for physical and psychological
      growth and development; any associated anomalies were noted. A detailed history
      of the patient's family, including the prenatal history, was obtained. Lesions
      were classified with the help of neuroimaging studies (skull x-ray, CT,
      ultrasonography, and MR imaging studies) and confirmed at surgery. RESULTS:
      Sixteen patients had nasofrontal, 9 had nasoethmoidal, and 3 had nasoorbital
      encephaloceles, and 12 patients had associated hydrocephalus. The modes of
      presentation were nasofrontal swelling, watering from the eyes, CSF leakage,
      fever, and vomiting. Parents of all the patients were ethnic tea garden workers.
      The average parental age at the time of marriage was 24 years for men and 18
      years for women. Consanguinity was present in 6 patients. Alcohol consumption and
      tobacco chewing were a common practice in both parents. A total of 42 surgical
      procedures were done in 16 patients, one of whom died of postoperative
      meningitis. The mean follow-up duration was 38 months (1-92 months). CONCLUSIONS:
      Anterior encephaloceles are rare in Western countries and other states in India,
      but this defect is more commonly seen among the ethnic tea garden workers in
      Assam. Transcranial repair is the treatment of choice. Unlike encephaloceles in
      other locations, anterior encephaloceles have a better clinical outcome after
      surgery.

PMID- 20043741
TI  - Mobile spinal ependymoma.
AB  - Mobile spinal tumors have been reported previously in the literature, with
      schwannomas as the most common form. A discrepancy between the location of the
      tumor in preoperative imaging and its actual position intraoperatively may lead
      to confusion. The authors present an unusual case of a mobile cauda equina
      ependymoma. Resection was complicated by cephalad migration of the tumor upon
      durotomy. Visualization was made possible by engaging a Valsalva maneuver in the
      patient under anesthesia, at which point the tumor was observed to migrate
      caudally into the operative field. Observation of this unique pathology is
      presented as potentially important knowledge for surgeons that might help prevent
      other unnecessary procedures such as a multilevel laminectomy.

PMID- 20043742
TI  - Solitary spinal epidural cavernous angiomas in children presenting with acute
      neurological symptoms caused by hemorrhage.
AB  - Spinal solitary epidural cavernous angiomas are rare benign vascular
      malformations, which occur even less frequently in children than in adults. It is
      uncommon to find such lesions without adjacent vertebral involvement.
      Occasionally, these lesions can lead to neurological symptoms through growth or
      due to intralesional hemorrhage. In this report the authors describe 2 children
      presenting with acute symptoms and neurological deficits caused by hemorrhage
      within solitary spinal epidural cavernous angiomas. A 13-year-old girl and a 9
      year-old girl, previously healthy, were admitted to the authors' department due
      to acute radicular pain and neurological deficits. In both cases MR imaging
      revealed a solitary epidural mass with signs of bleeding and compression of the
      spinal cord. Complete resection of the lesion via a dorsal approach was performed
      in both patients. The histological examination of the lesions revealed the
      characteristic structures of a cavernous angioma with hemosiderin deposits and
      acute hemorrhage. Both patients recovered fully after surgical removal of the
      lesions. Review of the literature confirmed that spinal epidural cavernous
      angiomas are extremely rare in the pediatric patient population, described
      currently in only 2 instances, but without acute hemorrhage. These cases suggest
      that epidural cavernous angiomas also have to be considered in the pediatric
      patient population in the differential diagnosis of intraspinal lesions with
      acute or progressive neurological symptoms. Microsurgical resection of these
      cavernous malformations is an effective and curative treatment option.

PMID- 20043743
TI  - Primary T-cell lymphoblastic lymphoma of the cavernous sinus.
AB  - The rare occurrence of T-cell lymphoblastic lymphoma as a primary tumor in the
      cavernous sinus is described. The patient, a 17-year-old girl, presented with
      right-sided ophthalmic and maxillary neuropathy and diplopia due to neuropathies
      of cranial nerves III and VI. An enhancing mass in the cavernous sinus was
      identified on MR imaging. Dexamethasone was prescribed but did not provide
      symptomatic relief. Rapid progression of symptoms led to open biopsy, and a
      diagnosis of T-cell lymphoblastic lymphoma was made. The patient promptly
      underwent aggressive chemotherapy in which a modified hyper-cyclophosphamide,
      vincristine, and dexamethasone without doxorubicin regimen with concurrent
      radiotherapy was used. The patient achieved complete remission and is currently
      completing the 2-year maintenance phase of chemotherapy.

PMID- 20043744
TI  - Rosette-forming glioneuronal tumors of the posterior fossa.
AB  - Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare,
      recently described WHO Grade I neoplasm. The authors report 6 examples of RGNT
      arising primarily from the cerebellar vermis. All the patients were female, and
      the mean age of presentation was 24.8 years. The original diagnoses included
      pilocytic astrocytoma, ependymoma, cerebellar dysembryoplastic neuroepithelial
      tumor (DNT), and oligodendroglioma. The cases showed classic pathological
      characteristics, although in 2 cases the lesions included DNT-like "floating
      neurons" involving Purkinje cells, a feature which has not been previously
      reported to the authors' knowledge. The clinical outcome was excellent with no
      recurrences after complete resection. These cases expand the known clinical and
      histological spectrum of this rare tumor type. Given the lack of fourth ventricle
      involvement in most of these cases, the authors suggest revising the name to RGNT
      of the posterior fossa.

PMID- 20043745
TI  - Simultaneous choroid plexus carcinoma and pilocytic astrocytoma in a pediatric
      patient.
AB  - Simultaneous primary brain tumors in pediatric patients without prior
      chemotherapy or radiotherapy, phacomatosis, or known familial history are a rare
      occurrence. The authors report the case of a 4-year-old boy with simultaneous
      choroid plexus carcinoma and pilocytic astrocytoma with features of
      oligodendroglioma. Magnetic resonance imaging studies revealed diffuse
      heterogeneously enhancing left intraventricular and posterior fossa tumors
      initially believed most consistent with multicentric choroid plexus carcinomas. A
      multiple staged resection was carried out for each tumor and gross-total
      resection was achieved. Upon gross inspection intraoperatively as well as
      postoperative histological analysis, 2 distinct simultaneous tumors were
      identified: choroid plexus carcinoma and pilocytic astrocytoma. To the authors'
      knowledge this is the first case report published identifying 2 distinct tumor
      types with similar radiological appearances in a pediatric patient with no prior
      history of radiotherapy, chemotherapy, or phacomatosis.

PMID- 20043746
TI  - Noninvasive localization of epileptogenic zones with ictal high-frequency
      neuromagnetic signals.
AB  - OBJECT: Recent reports suggest that high-frequency epileptic activity is highly
      localized to epileptogenic zones. The goal of the present study was to
      investigate the potential usefulness of noninvasive localization of high
      frequency epileptic activity for epilepsy surgery. METHODS: Data obtained in 4
      patients, who had seizures during routine magnetoencephalography (MEG) tests,
      were retrospectively studied. The MEG data were digitized at 4000 Hz, and 3D MR
      images were obtained. The magnetic sources were volumetrically localized with
      wavelet-based beamformer. The MEG results were subsequently compared with
      clinical data. RESULTS: The 4 patients had 1-4 high-frequency neuromagnetic
      components (110-910 Hz) in ictal and interictal activities. The loci of high
      frequency activities were concordant with intracranial recordings therein 3
      patients, who underwent presurgical evaluation. The loci of high-frequency ictal
      activities were in line with semiology and neuroimaging in all 4 of the patients.
      High-frequency epileptic activity was highly localized to the epileptogenic
      zones. CONCLUSIONS: High-frequency epileptic activity can be volumetrically
      localized with MEG. Source analysis of high-frequency neuromagnetic signals has
      the potential to determine epileptogenic zones noninvasively and preoperatively
      for epilepsy surgery.

PMID- 20043747
TI  - Seizure control outcomes after resection of dysembryoplastic neuroepithelial
      tumor in 50 patients.
AB  - OBJECT: Dysembryoplastic neuroepithelial tumors (DNETs) are a subset of
      relatively rare glioneuronal tumors that typically present with epilepsy during
      childhood. The authors' aim was to identify factors that predict seizure control
      following excision. METHODS: The authors reviewed the cases of 50 patients who
      underwent resection of DNETs at the University of California, San Francisco,
      between 1990 and 2006. Demographic, seizure history, radiographic, and
      histopathological data were collected and analyzed for statistical association
      with postoperative seizure control. RESULTS: Of the 50 patients, 86% presented
      with intractable epilepsy. The median age at surgery was 21 years (range 4-46
      years; 40% were < 18 years old at time of surgery), with a median duration of 8
      years from onset of seizures (24% were adult-onset seizures). Fifty-two percent
      of the cases were associated with adjacent focal cortical dysplasia. Complete
      resection was achieved in 78% of cases. Intraoperative electrocorticography in 23
      patients identified extralesional interictal activity in 16 cases, which led to
      extended lesionectomy or lobectomy. The remaining patients underwent lesionectomy
      alone. The median follow-up was 5.6 years, during which time tumor progression
      occurred after subtotal resection. The proportional estimates of seizure freedom
      (Engel Class I outcome) were 0.86 at 1 year and 0.85 at 5 years. Seizure freedom
      was predicted by complete or extended resection (OR 1.68, 95% CI 1.39-2.03; p <
      0.0001) and extratemporal location (OR 1.20, 95% CI 1.02-1.42; p = 0.03) on
      multivariate analysis. Secondary analysis for intraoperative electrocorticography
      cases demonstrated that seizure outcome was better when extralesional spiking
      foci were detected (94% seizure free) compared with when they were absent (43%
      seizure free). CONCLUSIONS: Excision of DNETs and, when present, adjacent
      dysplastic cortex was highly effective for seizure control. Excellent seizure
      free outcomes and tumor control were seen with lesionectomy alone in most cases.
      Electrocorticography with extended resection was useful for patients with
      pharmacoresistant epilepsy.

PMID- 20043748
TI  - A single-center experience with symptomatic postoperative calvarial growth
      restriction after extended strip craniectomy for sagittal craniosynostosis.
AB  - OBJECT: Sagittal synostosis accounts for the most common form of
      craniosynostosis, occurring with an incidence of 1 in 2000-5000 live births. In
      most cases of single-suture, nonsyndromic sagittal synostosis, a single operation
      is all that is required to achieve a reasonable cosmetic result. However, there
      are a number of patients who may experience symptomatic postoperative calvarial
      growth restriction secondary to fibrosis of newly formed bone and pericranium
      that replace the surgically removed sagittal suture, or due to fusion of other
      previously open sutures leading to increased intracranial pressure, necessitating
      a second operation. METHODS: A retrospective review was conducted of all cases
      involving infants who had undergone an extended sagittal strip craniectomy with
      bilateral parietal wedge osteotomies at our institution between 1990 and 2006 for
      single-suture, nonsyndromic sagittal craniosynostosis. The frequency with which
      subsequent operations were required for cranial growth restriction was then
      defined. RESULTS: There were a total of 164 patients with single-suture
      nonsyndromic sagittal synostosis. Follow-up data were available for 143 of these
      patients. The average age at time of initial operation was 5.25 months, and the
      mean duration of follow-up was 43.85 months. There were 2 patients (1.5%) who
      required a second operation for symptomatic postoperative calvarial growth
      restriction. CONCLUSIONS: Recurrence of synostosis with resultant increased
      intracranial pressure in cases of single-suture, nonsyndromic sagittal
      craniosynostosis is an uncommon event, but does occur sporadically and
      unpredictably. Therefore, we recommend routine neurosurgical follow up for at
      least 5 years, with regular ophthalmological examinations to assess for
      papilledema.

PMID- 20043749
TI  - Recurrence of fibrous hamartoma of infancy excised 14 years after the primary
      surgery.
AB  - Fibrous hamartoma of infancy is a rare, benign, superficial soft-tissue mass. It
      usually occurs within the first 2 years of life at the axial regions, upper arms,
      and external genital areas. There have been some recurrences within the 1st year
      of the surgery, although no cases have been reported to recur after 1 year. The
      authors present a recurrent case of fibrous hamartoma of infancy 14 years after
      the primary surgery, and they show the clinical and histopathological findings.

PMID- 20043750
TI  - Pontine gliomas.

PMID- 20043751
TI  - Induction of type 2 responses by schistosome worms during prepatent infection.
AB  - During natural schistosome infection, the induction of T helper type 2 (Th2)
      responses has been ascribed to parasite eggs, because exposure of the host to
      this life-cycle stage elicits a polarized Th2 response to egg antigens. In the
      present study, we show that schistosome worms also elicit systemic, antigen
      specific type 2 responses during prepatent infection, before egg deposition
      begins. CD4(+) T cells producing interleukin (IL)-4 were induced by both male and
      female worms during single-sex infections, demonstrating that this response is
      independent of exposure to eggs. The Th2 response was accompanied by production
      of immunoglobulin E and the sensitization of circulating basophils to produce
      additional IL-4 in response to schistosome antigens. Together, our data show that
      schistosome worms establish an immunologic milieu where CD4(+) T cells and
      basophils are both primed to produce IL-4 before eggs are laid, suggesting that
      worms play a role in establishment of the Th2 response that is critical for host
      survival and parasite transmission.

PMID- 20043753
TI  - Comparative accuracy of 3 monoclonal stool tests for diagnosis of Helicobacter
      pylori infection among patients with dyspepsia.
AB  - BACKGROUND: Well-devised studies comparing new but different monoclonal fecal
      tests for diagnosing Helicobacter pylori infection are scarce. The objective of
      this study was to compare the diagnostic accuracy of 3 monoclonal stool tests: 2
      rapid in-office tools-RAPID Hp StAR and ImmunoCard STAT! HpSA-and an enzyme
      immunoassay test-Amplified IDEIA Hp StAR-for diagnosing H. pylori infection prior
      to eradication treatment. METHODS: Diagnostic reliability was evaluated in 199
      untreated consecutive patients with dyspeptic symptoms. The gold standard for
      diagnosing H. pylori infection was defined as the concordance of the rapid urease
      test, histopathology, and urea breath test. Readings of immunochromatographic
      tests were performed by 2 different observers. Sensitivity, specificity, positive
      and negative predictive values, and 95% confidence intervals were calculated.
      Sensitivity and specificity were compared using the McNemar test. RESULTS: The
      sensitivity and specificity of Amplified IDEIA Hp StAR were 90% and 89%,
      respectively. This enzyme immunoassay test was significantly more sensitive than
      ImmunoCard STAT! HpSA and more specific than RAPID Hp StAR. The sensitivity and
      specificity of RAPID Hp StAR were 91% and 80%, respectively, according to
      observer 1, and 92% and 76%, respectively, according to observer 2. It was
      significantly more sensitive and less specific than ImmunoCard STAT! HpSA. The
      sensitivity and specificity of ImmunoCard STAT! HpSA were 69% and 90%,
      respectively, according to observer 1, and 74% and 89%, respectively, according
      to observer 2. CONCLUSIONS: Amplified IDEIA Hp StAR seems to be the most accurate
      stool test for diagnosing H. pylori for patients with dyspeptic symptoms. The
      currently available in-office tests obtain slightly less reliable results.

PMID- 20043752
TI  - Cost-effectiveness of tenofovir as first-line antiretroviral therapy in India.
AB  - BACKGROUND: World Health Organization guidelines for antiretroviral treatment
      (ART) in resource-limited settings recommend either stavudine or tenofovir as
      part of initial therapy. We evaluated the clinical outcomes and cost
      effectiveness of first-line ART using tenofovir in India, compared with current
      practice using stavudine or zidovudine. METHODS: We used a state-transition model
      of human immunodeficiency virus (HIV) disease to examine strategies using
      different nucleoside reverse-transcriptase inhibitors, combined with lamivudine
      and nevirapine, compared with no ART: (1) stavudine, (2) stavudine with
      substitution by zidovudine after 6 months, (3) zidovudine, and (4) tenofovir.
      Data were from the Y. R. Gaitonde Centre for AIDS Research and Education in
      Chennai, India, and published studies. Results. Discounted mean per person
      survival was 36.9 months (40.2 months undiscounted) with no ART, 115.5 months
      (145.3) with stavudine-containing ART, 115.7 months (145.6) with stavudine and 6
      month zidovudine substitution, 115.8 months (145.6) with zidovudine-containing
      ART, and 125.8 months (162.0) with initial tenofovir. Discounted lifetime medical
      costs were $610 with no ART and ranged from $5580 with stavudine-containing ART
      to $5720 with zidovudine-containing ART. Initial tenofovir had an incremental
      cost-effectiveness ratio of $670 per year of life saved, compared with no ART,
      and was more economically efficient than the other regimens. RESULTS: were most
      sensitive to variations in the costs of first-line tenofovir, access to
      additional ART after treatment failure, and quality of life adjustment.
      CONCLUSIONS: Using tenofovir as part of first-line ART in India will improve
      survival, is cost-effective by international standards, and should be considered
      for initial therapy for HIV-infected patients in India.

PMID- 20043754
TI  - Ca2+ and cAMP signaling in human embryonic stem cell-derived dopamine neurons.
AB  - Human embryonic stem (hES) cell differentiation into dopamine neurons is
      considered a promising strategy for cell replacement therapy in Parkinson's
      disease, yet the functional properties of hES cell-derived dopamine neurons
      remain poorly defined. The objective of this study was to characterize
      intracellular calcium (Ca(2+)) and sub-plasma membrane cyclic AMP-signaling
      properties in hES cell-derived dopamine neurons. We found that hES cell-derived
      dopamine neurons and neural progenitors raised Ca(2+) from intra- and
      extracellular compartments in response to depolarization, glutamate, ATP, and
      dopamine D(2) receptor activation, while undifferentiated hES cells only
      mobilized Ca(2+) from intracellular stores in response to ATP and D(2) receptor
      induced activation. Interestingly, we also found that hES cell-derived dopamine
      neurons in addition to primary ventral midbrain dopamine neurons were more prone
      to release Ca(2+) from intracellular stores than non-dopamine neurons following
      treatment with the neuropeptide neurotensin. Furthermore, hES cell-derived
      dopamine neurons showed cAMP elevations in response to forskolin and 3-isobutyl
      methylxanthine, similar to primary dopamine neurons. Taken together, these
      results unravel the temporal sequence by which hES cells acquire Ca(2+) and cAMP
      signaling competence during dopamine differentiation.

PMID- 20043755
TI  - Anterior fixation of odontoid fractures in an elderly population.
AB  - OBJECT: Fractures of the odontoid process are the most common fractures of the
      cervical spine in patients over the age of 70 years. The incidence of fracture
      nonunion in this population has been estimated to be 20-fold greater than that in
      patients under the age of 50 years if surgical stabilization is not used.
      Anterior and posterior approaches have both been advocated, with excellent
      results reported, but surgeons should understand the drawbacks of the various
      techniques before employing them in clinical practice. METHODS: A retrospective
      review was undertaken to identify patients who had direct fixation of an odontoid
      fracture at a single institution from 1991 to 2006. Patients were followed up
      using flexion-extension radiographs, and stability was evaluated as bone union,
      fibrous union, or nonunion. Patients with bone or fibrous union were classified
      as stable. In addition, the incidence of procedure- and nonprocedure-related
      complications was extracted from the medical record. RESULTS: Of the 57 patients
      over age 70 who underwent placement of an odontoid screw, 42 underwent follow-up
      from 3 to 62 months (mean 15 months). Stability was confirmed in 81% of these
      patients. In patients with fixation using 2 screws, 96% demonstrated stability on
      radiographs at final follow-up. Only 56% of patients with fixation using a single
      screw demonstrated stability on radiographs. In the immediate postoperative
      period, 25% of patients required a feeding tube and 19% had aspiration pneumonia
      that required antibiotic treatment. CONCLUSIONS: Direct fixation of Type II
      odontoid fractures showed stability rates > 80% in this challenging population.
      Significantly higher stabilization rates were achieved when 2 screws were placed.
      The anterior approach was associated with a relatively high dysphagia rate, and
      patients must be counseled about this risk before surgery.

PMID- 20043756
TI  - Symptomatic occipitocervical paracondylar process.
AB  - A paracondylar process is a bony exostosis that arises from the skull base
      lateral to the occipital condyle and extends inferiorly toward the transverse
      process of the atlas. This congenital anomaly can vary in size from a small
      protuberance to an elongated process articulating with an epitransverse process
      arising from C-1. Typically, a paracondylar process is an incidental finding
      described in anatomical studies. The authors report on a patient with a
      symptomatic paracondylar process articulating with an epitransverse process that
      caused occipitocervical pain. Resection of the paracondylar and epitransverse
      processes completely relieved the patient's pain.

PMID- 20043757
TI  - Transoral robotic surgery of craniocervical junction and atlantoaxial spine: a
      cadaveric study.
AB  - OBJECT: The goal of this study was to determine the potential role and current
      limitations of the da Vinci surgical robot in transoral decompression of
      craniocervical junction (CCJ). METHODS: The da Vinci Surgical System was used in
      2 cadaver heads with neck and clavicles intact. Both neurosurgeons and
      otolaryngologists familiar with the open microscopic procedure, as well as the
      transoral robotic surgical procedure, undertook dissection and decompression of
      the CCJ. RESULTS: The robotic system provided superb illumination and 3D depth
      perception even several centimeters deep to the posterior oropharyngeal mucosa.
      The 30 degrees endoscope improved cephalad visualization, eliminating the need to
      split the soft palate for exposure of the lower clivus. The "intuitive" nature of
      the da Vinci surgical robot arms provided an advantage in allowing the ability to
      suture the dura mater in a deep, dark corridor. Because visualization was
      excellent, tremor-free closure was possible. CONCLUSIONS: The authors' findings
      suggest that transoral robotic surgery, with the da Vinci robot system, holds
      great potential for decompression of the CCJ as well as resection of both extra-
      and intradural tumors of this region. Further instrument development is necessary
      and continued investigation is warranted.

PMID- 20043758
TI  - Cruciate paralysis secondary to traumatic atlantooccipital dislocation.
AB  - Cruciate paralysis is a clinical phenomenon thought to result from injury to
      decussating pyramidal tract fibers at the cervicomedullary junction, producing
      clinical findings of upper-extremity weakness out of proportion to the lower
      extremities. The authors present, to their knowledge, the first reported case of
      cruciate paralysis resulting from atlantooccipital dislocation.

PMID- 20043759
TI  - Surgical challenges associated with the morphology of the spinal accessory nerve
      in the posterior cervical triangle: functional or structural?
AB  - OBJECT: The spinal accessory nerve (SAN) has been reported to have a distinctly
      coiled appearance in its course through the posterior cervical triangle of the
      neck. As this is unusual compared with other peripheral nerves including the
      cranial nerves, the present histological analysis was performed to further
      elucidate the reason for this anatomy with potential application in nerve injury
      and repair. METHODS: Ten adult cadavers underwent dissection of the neck. The SAN
      was harvested proximally and within the posterior cervical triangle. For
      comparison with other cranial nerves within the neck, the cervical vagus and
      hypoglossal nerves were also harvested. All nerves underwent histological
      analysis. Additionally, 2 human fetuses (11 and 20 weeks' gestation) underwent
      examination of the SAN in the posterior cervical triangle, and 3 randomly
      selected specimens were submitted for electromicroscopy. RESULTS: All SANs were
      found to have a straight gross configuration proximal to the posterior triangle
      and a coiled appearance within this geometrical area. Histologically, no
      differences were identified for the SAN in these 2 locations (that is, proximal
      to and within the posterior cervical triangle). The histology of the SAN both
      with routine analysis and electron microscopy was similar in both regions and to
      nerves used as controls (for example, vagus and hypoglossal nerves).
      Interestingly, both fetal specimens were found to have coiled SANs in the
      posterior cervical triangle. CONCLUSIONS: Based on this study, it appears that
      the tortuous course of the SAN in the posterior triangle arises from functional
      as opposed to structural forces. It is hoped that this analysis will provide some
      insight into the nature behind the morphology observed in the SAN within the
      posterior cervical triangle and aid in future investigations regarding its
      injury. Moreover, such a coiled nature of this nerve may assist the neurosurgeon
      in identifying it during, for example, neurotization procedures.

PMID- 20043760
TI  - A safe approach to explore/identify the V(2) segment of the vertebral artery
      during anterior approaches to cervical spine and/or arterial repairs: anatomical
      study.
AB  - OBJECT: The purpose of this study was to find a landmark according to which the
      surgeon can dissect the cervical spine safely, with the lowest possibility of
      damaging the vertebral artery (VA) during anterior approaches to the cervical
      spine or the VA. METHODS: The "safe zone" for each level of the cervical spine
      was described as an area where the surgeon can start from the midline in that
      zone and dissect the soft tissue laterally to end up on the transverse process
      and cross the VA while still on the transverse process. In other words, safe zone
      signifies the narrowest width of the transverse process at each level. In such an
      approach, the VA is protected from the inadvertent deep penetration of the
      instruments by the transverse process. The surgical safe zone for each level was
      the common area among at least 95% of the safe zones for that level. For the
      purpose of defining the upper and lower borders of the safe zone for each level,
      the line passing from the upper vertebral border perpendicular to the midline
      (upper vertebral border line) was used as a reference. Cervical spines of 64
      formalin-fixed cadavers were dissected. The soft tissue in front of the
      transverse process and intertransverse space was removed. Digital pictures of the
      specimens were taken before and after removal of the transverse processes, and
      the distance to the upper and lower border of the safe zone from the upper
      vertebral border line was measured on the digital pictures with Image J software.
      The VA diameter and distance from the midline at each level were also measured.
      To compare the means, the authors used t-test and ANOVA. RESULTS: The surgical
      safe zone lies between 1 mm above and 1 mm below the upper vertebral border at
      the fourth vertebra, 2 mm above and 1 mm below the upper vertebral border at the
      fifth vertebra, and 1 mm above and 2 mm below the upper vertebral border of the
      sixth vertebra. The VA was observed to be tortuous in 13% of the intertransverse
      spaces. There is a positive association between disc degeneration and tortuosity
      of the VA at each level (p < 0.001). The artery becomes closer to the midline (p
      < 0.001) and moves posteriorly during its ascent. CONCLUSIONS: Dissection of the
      soft tissue off the bone along the surgical safe zone and removal of the
      transverse process afterward can be a practical and safe approach to avoid artery
      lacerations. The findings in the present study can be used in anterior approaches
      to the cervical spine, especially when the tortuosity of the artery mandates
      exposure of the VA prior to uncinate process resection, tumor excision, or VA
      repair.

PMID- 20043761
TI  - "Skip" corpectomy in the treatment of multilevel cervical spondylotic myelopathy
      and ossified posterior longitudinal ligament.
AB  - OBJECT: The authors reviewed the results of "skip" corpectomy in 29 patients with
      multilevel cervical spondylotic myelopathy (CSM) and ossified posterior
      longitudinal ligament (OPLL). METHODS: The skip corpectomy technique, which is
      characterized by C-4 and C-6 corpectomy, C-5 osteophytectomy, and C-5 vertebral
      body preservation, was used for decompression in patients with multilevel CSM and
      OPLL. All patients underwent spinal fixation using C4-5 and C5-6 grafts, and
      anterior cervical plates were fixated at C-3, C-5, and C-7. RESULTS: The mean
      preoperative Japanese Orthopaedic Association score increased from 13.44 +/- 2.81
      to 16.16 +/- 2.19 after surgery (p < 0.05). The cervical lordosis improved from
      1.16 +/- 11.74 degrees to 14.36 +/- 7.85 degrees after surgery (p < 0.05). The
      complications included temporary hoarseness in 3 cases, dysphagia in 1 case, C-5
      nerve palsy in 1 case, and C-7 screw pullout in 1 case. The mean follow-up was
      23.2 months. The final plain radiographs showed improved cervical lordosis and
      fusion in all cases. CONCLUSIONS: The authors conclude that the preservation of
      the C-5 vertebral body provided an additional screw purchase and strengthened the
      construct. The results of the current study demonstrated effectiveness and safety
      of the skip corpectomy in patients with multilevel CSM and OPLL.

PMID- 20043762
TI  - Ectopic bone.

PMID- 20043763
TI  - Symptomatic ectopic bone formation after off-label use of recombinant human bone
      morphogenetic protein-2 in transforaminal lumbar interbody fusion.
AB  - OBJECT: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been
      approved for use in the lumbar spine in conjunction with the lumbar tapered cage.
      However, off-label use of this osteoinductive agent is observed with anterior
      fusion applications as well as with both posterior lumbar interbody fusion and
      transforaminal lumbar interbody fusion (TLIF). Complications using rhBMP-2 in the
      cervical spine have been reported. Although radiographic evidence of ectopic bone
      in the lumbar spine has been described following rhBMP-2 use, this finding was
      not previously believed to be of clinical relevance. METHODS: This study was a
      retrospective review of 4 patients who underwent minimally invasive spinal TLIF
      (MIS-TLIF) in which bone fusion was augmented with rhBMP-2 applied to an
      absorbable collagen sponge. Case presentations, operative findings, imaging data,
      and follow-up findings were reviewed. RESULTS: Four cases with delayed
      symptomatic neural compression following the off-label use of rhBMP-2 with MIS
      TLIF were identified. CONCLUSIONS: Although previously believed to be only a
      radiographic finding, the development of ectopic bone following rhBMP-2 use in
      lumbar fusion can be clinically significant. This paper describes 4 cases of
      delayed neural compression following MIS-TLIF. The reader should be aware of this
      potential complication following the off-label use of rhBMP-2 in the lumbar
      spine.

PMID- 20043764
TI  - Sagittal whole-spine magnetic resonance imaging in 750 consecutive outpatients:
      accurate determination of the number of lumbar vertebral bodies.
AB  - OBJECT: When the number of lumbar and sacral vertebrae is being assessed,
      variations from typical lumbosacral anatomy may confuse the practitioner,
      potentially leading to significant clinical errors. In this study, the authors
      describe the statistical variation in lumbar spine anatomy in an outpatient
      imaging setting, evaluate the potential implications for clinical practice based
      on the variation in the number of lumbar-type vertebrae identified, and recommend
      a method for rapidly determining the number of lumbar spine vertebral bodies
      (VBs) in outpatients referred for lumbar spine MR imaging. METHODS: A total of
      762 patients (male and female) who presented with low back-related medical
      conditions underwent whole-spine MR imaging in an outpatient setting. RESULTS:
      The high-speed whole-spine evaluation was successful for determining the number
      of lumbar-type VBs in 750 (98%) of 762 consecutive patients. The sagittal whole
      spine 3-T MR imaging system images obtained between the beginning of January 2005
      and the end of February 2007 were reviewed. The VBs were counted successively
      from the level of C-2 inferiorly to the intervertebral disc below the most
      inferior lumbar-type VB. Numbers of disc herniations were also evaluated in the
      context of the number of VBs. CONCLUSIONS: One in 5 of these outpatients did not
      have 5 lumbar-type vertebrae: 14.5% had 6; 5.3% had 4; and 1 (0.13%) had the rare
      finding of 3 lumbar-type vertebrae. Two-thirds of the individuals with 6 lumbar
      type vertebrae were male and two-thirds of the individuals with 4 lumbar-type
      vertebrae were female. Sagittal whole-spine MR imaging can be performed rapidly
      and efficiently in the majority of patients (98%), and provides improved accuracy
      for the determination of the number of lumbar-type VBs. A supplementary coronal
      MR, Ferguson view radiograph or intraoperative fluoroscopic determination for the
      presence of lumbosacral transitional vertebrae may add additional information
      when indicated for clinical treatment or surgical planning.

PMID- 20043765
TI  - Magnetic resonance imaging and outcome.

PMID- 20043766
TI  - Long-term surgical outcome and risk factors in patients with cervical myelopathy
      and a change in signal intensity of intramedullary spinal cord on Magnetic
      Resonance imaging.
AB  - OBJECT: The goal of this study was to determine the long-term clinical
      significance of and the risk factors for intramedullary signal intensity change
      on MR images in patients with cervical compression myelopathy (CCM), an entity
      most commonly seen with cervical spondylotic myelopathy and ossification of the
      posterior longitudinal ligament (OPLL). METHODS: One hundred seventy-four
      patients with CCM but without cervical disc herniation, severe OPLL (in which the
      cervical canal is < 10 mm due to OPLL), or severe kyphotic deformity (> 15
      degrees of cervical kyphosis) who underwent surgery were initially selected. One
      hundred eight of these patients were followed for > 36 months, and the 71
      patients who agreed to MR imaging examinations both pre- and postsurgery were
      enrolled in the study (the mean follow-up duration was 60.6 months). All patients
      underwent cervical laminoplasty. The authors used the Japanese Orthopaedic
      Association (JOA) score and recovery ratio for evaluation of pre- and
      postoperative outcomes. The multifactorial effects of variables such as age, sex,
      a history of smoking, diabetes mellitus, duration of symptoms, postoperative
      expansion of the high signal intensity area of the spinal cord on MR imaging,
      sagittal arrangement of the cervical spine, presence of ventral spinal cord
      compression, and presence of an unstable cervical spine were studied. RESULTS:
      Change in intramedullary signal intensity was observed in 50 of the 71 patients
      preoperatively. The pre- and postoperative JOA scores and the recovery ratio were
      significantly lower in the patients with signal intensity change. The mean JOA
      score of the upper extremities was also significantly lower in these patients.
      Twenty-one patients showed hypointensity in their T1-weighted images, and a
      nonsignificant correlation was observed between intensity in the T1-weighted
      image and the mean JOA score and recovery ratio. The risk factors for signal
      intensity change were instability of the cervical spine (OR 8.255, p = 0.037) and
      ventral spinal cord compression (OR 5.502, p < 0.01). Among these patients, 16
      had postoperative expansion of the high signal intensity area of the spinal cord.
      The mean JOA score and the recovery ratio at the final follow-up were
      significantly lower in these patients. The risk factor for postoperative
      expansion of the high signal intensity area was instability of the cervical spine
      (OR 5.509, p = 0.022). No significant correlation was observed between signal
      intensity on T1-weighted MR images and postoperative expansion of the
      intramedullary high signal intensity area on T2-weighted MR images. CONCLUSIONS:
      Long-term clinical outcome was significantly worse in patients with
      intramedullary signal intensity changes on MR images. The risk factors were
      instability of the cervical spine and severe ventral spinal compression. The long
      term clinical outcome was also significantly worse in patients with postoperative
      expansion of the high signal intensity area. The fact that cervical instability
      was a risk factor for the postoperative expansion of the high signal intensity
      indicates that this high signal intensity area occurred, not only from necrosis
      secondary to ischemia of the anterior spinal artery, but also from the repeated
      minor traumas inflicted on the spinal cord from an unstable cervical spine. The
      long-term neurological outcome found in the preliminary study of patients with
      CCM who had cervical instability and intramedullary signal intensity changes on
      MR images suggests that surgical treatment should include posterior fixation
      along with cervical laminoplasty or anterior spinal fusion.

PMID- 20043767
TI  - Catheter-tip mass mimicking a spinal epidural hematoma.
AB  - As > 95,000 spinal drug-delivery devices have been implanted since their
      inception in the 1980s, the recognition of associated adverse effects is
      essential. Since 1985, numerous reports have described the presence of catheter
      tip granulomas. In the current case, the authors describe a less frequent
      complication of epidural bupivacaine precipitation. Regardless of origin, these
      unusual lesions have been increasingly recognized as a rare but potentially
      devastating complication of intrathecal infusions. A 34-year-old woman with an
      intrathecal pain-pump delivering fentanyl, bupivacaine, and clonidine for
      thoracic outlet syndrome presented with rapidly progressive neurological deficits
      and increasing neck and upper-extremity pain. Neuroimaging disclosed a C7-T1 mass
      that was thought to be a hematoma that occurred after a recent epidural steroid
      injection. On emergency surgical decompression by laminectomy, a chalky mass
      containing viscous fluid was identified surrounding an epidurally located
      catheter. Histopathological examination revealed a proteinaceous mass consistent
      with drug precipitate enveloped by fibrosis and mild inflammation.
      Postoperatively, the patient recovered with minimal neurological deficit. The
      presentation and clinical relevance are discussed in conjunction with a review of
      the pertinent literature. Catheter-tip masses are a rare complication of
      implantable drug-delivery devices occurring in < 3% of all patients with
      intrathecal catheters. Regardless of the anatomical site, the most common
      presenting features are neurological deficits, worsening pain, and increasing
      requirements for pain medication. Expedient diagnosis and management are
      essential for physicians treating patients with spinal infusion devices to
      prevent significant neurological sequelae. Further investigation is warranted
      regarding the use of bupivacaine as an adjunct in permanent spinal infusion
      systems.

PMID- 20043768
TI  - Posterior decompression surgery for extraforaminal entrapment of the fifth lumbar
      spinal nerve at the lumbosacral junction.
AB  - OBJECT: In this paper, the authors' goal was to elucidate the clinical features
      and results of decompression surgery for extraforaminal stenosis at the
      lumbosacral junction. METHODS: Twenty-eight patients with severe leg pain caused
      by extraforaminal stenosis at the lumbosacral junction (18 men and 10 women; mean
      age 68.2 +/- 8.9 years) were treated by posterior decompression without fusion
      using a microendoscope in 19 patients and a surgical microscope or loupe in 9
      patients. The decompression procedures consisted of partial resection of the
      sacral ala, the L-5 transverse process, and the L5-S1 facet joint along the L-5
      spinal nerve. The following items were investigated: 1) preoperative neurological
      findings; 2) preoperative radiological findings, including plain radiographs, CT
      scans, selective radiculography of L-5; 3) surgical outcome as evaluated using
      the Japanese Orthopaedic Association scale for low-back pain (JOA score); and 4)
      need for revision surgery. RESULTS: All patients presented with neurological
      deficits compatible with a diagnosis of L-5 radiculopathy such as weakness of the
      extensor hallucis longus muscle and sensory disturbance in the L-5 area together
      with neurogenic claudication. On plain radiographs, 21 patients (75%) and 17
      patients (60.7%) exhibited lumbar scoliosis (>or= 5 degrees) and wedging of the
      L5-S1 intervertebral space (>or= 3 degrees), respectively. The CT scans
      demonstrated marked osteophyte formation at the posterolateral margin of the L5
      S1 vertebral bodies, and a selective L-5 nerve root block was effective in all
      patients. All patients reported pain relief immediately after surgery. The mean
      JOA scores were 11.3 +/- 3.8 before surgery and 24.3 +/- 3.4 at the time of the
      final follow-up examination; the recovery rate was 68.6 +/- 16.5%. The mean
      estimated blood loss was 66.6 +/- 98.6 ml, and the mean surgical time was 135.3
      +/- 46.5 minutes. No significant difference in the recovery rate of the JOA
      scores or in the surgical time and blood loss was observed between the 2 surgical
      approaches. Four patients underwent revision posterior interbody fusion for the
      recurrence of radicular pain as a result of intraforaminal stenosis in 3 patients
      and insufficient decompression of the extraforaminal area in the remaining
      patient at an average of 19.5 months after surgery. CONCLUSIONS: Extraforaminal
      stenosis at the lumbosacral junction is a rare but distinct pathological
      condition causing L-5 radiculopathy. Decompression surgery without fusion using a
      microendoscope or a surgical microscope/loupe is a feasible and less invasive
      surgical option for elderly patients with extraforaminal stenosis at the
      lumbosacral junction.

PMID- 20043769
TI  - Revision of transforaminal lumbar interbody fusion using anterior lumbar
      interbody fusion: a biomechanical study in nonosteoporotic bone.
AB  - OBJECT: Transforaminal lumbar interbody fusion (TLIF) is a popular fusion
      technique for treating chronic low-back pain. In cases of interbody nonfusion,
      revision techniques for TLIF include anterior lumbar interbody fusion (ALIF)
      approaches. Biomechanical data of the revision techniques are not available. The
      purpose of this study was to compare the immediate construct stability, in terms
      of range of motion (ROM) and neutral zone (NZ), of a revision ALIF procedure for
      an unsuccessful TLIF. An in vitro biomechanical comparison of TLIF and its ALIF
      revision procedure was conducted on cadaveric nonosteoporotic human spine
      segments. METHODS: Twelve cadaveric lumbar motion segments with normal bone
      mineral density were loaded in unconstrained axial torsion, lateral bending, and
      flexion-extension under 0.05 Hz and +/- 6-nm sinusoidal waveform. The specimens
      underwent TLIF (with posterior pedicle fixation) and anterior ALIF (with intact
      posterior fixation). Multidirectional flexibility testing was conducted following
      each step. The ROM and NZ data were measured and calculated for each test.
      RESULTS: Globally, the TLIF and revision ALIF procedures significantly reduced
      ROM and NZ compared with that of the intact condition. The revision ALIF
      procedures achieved similar ROM as the TLIF procedure. CONCLUSIONS: Revision ALIF
      maintained biomechanical stability of TLIF in nonosteoporotic spines. Revision
      ALIF can be performed without sacrificing spinal stability in cases of intact
      posterior instrumentation.

PMID- 20043770
TI  - Smaller facet effusion in association with restabilization at the time of
      operation in Japanese patients with lumbar degenerative spondylolisthesis.
AB  - OBJECT: The objective of this study was to assess, in patients with degenerative
      lumbar spondylolisthesis, which factors determine whether the involved disc
      levels were restabilized or remained unstable at the time of operation using
      multifactorial analysis. METHODS: A total of 195 consecutive patients who had
      received laminectomy with or without fusion at our hospital between 2003 and 2007
      for progressed degenerative spondylolisthesis (slip percentage > 10% at lateral
      flexion position) with spinal canal stenosis participated in this study. Sagittal
      plane unstable motion was defined according to the criteria that translatory
      displacement was > 4 mm (translatory hypermobility) or rotatory displacement was
      > 10 degrees (rotatory hypermobility). There were 52 unstable cases (including 23
      translatory and 43 rotatory hypermobility cases) and 143 stable cases. Nine
      parameters were investigated retrospectively as candidate factors: age, sex, body
      mass index, disc level, grade of disc degeneration, grade of disc spur formation,
      facet effusion size, length of facet spur formation, and angle between facets.
      The differences in the candidate factors between the unstable and stable group,
      together with the association between translatory or rotatory displacements and
      factors other than sex and disc level, were investigated. Multivariate logistic
      regression analysis was also used to determine independent factors for the
      presence of unstable motion at the time of operation. RESULTS: The unstable group
      had significantly greater facet effusion size (p < 0.001) than the stable group.
      There were no significant differences between the 2 groups in age, sex, body mass
      index, disc level, grade of disc degeneration, grade of disc spur formation,
      length of facet spur formation, or angle between facets. Multiple regression
      analysis for all candidate factors (except for sex and disc level) indicated that
      translatory displacement significantly correlated with facet effusion size
      positively (p < 0.001), and that rotatory displacement significantly correlated
      with facet effusion size positively (p < 0.001) and with age (p = -0.042) and
      grade of disc degeneration (p = -0.033) negatively. Logistic regression analysis
      for all candidate factors demonstrated that increased facet effusion size (OR
      1.656, 95% CI 1.182-2.321) was the only independent factor for the presence of
      unstable motion at the time of operation. Facet effusion size had high negative
      but low positive predictive value in determining unstable motion at the time of
      operation. One of the reasons for the low positive predictive value was the
      association between facet spur formation and restabilization of the segments in
      the patients with greater facet effusion. CONCLUSIONS: Facet effusion size was
      associated with the determination of whether the affected disc was stabilized or
      remained unstable at the time of operation. In particular, a smaller facet
      effusion size strongly suggested that the affected disc had been restabilized in
      the patients with lumbar degenerative spondylolisthesis.

PMID- 20043771
TI  - Evidence that atypical juxtafacet cysts are joint derived.
AB  - OBJECT: Juxtafacet cysts (JFCs) in usual locations have recently been shown to
      have joint connections. The pathogenesis of JFCs in unusual locations has
      remained obscure. The authors hypothesize that all JFCs, including atypical ones,
      are joint derived. METHODS: In this study the authors sought to explain the
      occurrence and formation of clinical outliers of spinal JFCs. In Part I, they
      performed an extensive literature search to identify case reports of spinal
      intraneural cysts that have been unappreciated despite the fact that they should
      occur. In Part II, they studied far-lateral (extraforaminal) cysts treated at
      their institution and reported in the literature. The presence of a joint
      connection was specifically looked for since this finding has not been widely
      appreciated. RESULTS: In Part I, 3 isolated case reports of spinal intraneural
      JFCs without reported joint connections were identified: 2 involving L-5 and 1, C
      8. In Part II, 6 cases involving patients with far-lateral JFCs treated at the
      authors' institution were reviewed and all 6 had joint connections. Two of these
      cases had been previously published, although their joint connections were not
      appreciated. In 2 of the newly reported cases, arthrography confirmed a
      communication between the facet and the cyst. Only 1 of 5 cases in the literature
      had a recognized joint connection. CONCLUSIONS: The authors believe that all JFCs
      are joint derived. This explanation for intraneural and extraneural JFCs in
      typical locations would be consistent with the unified articular (synovial)
      theory and the pathogenesis for intraneural and extraneural ganglion cyst
      formation in the limbs. Facet joints appear no different from other synovial
      joints occurring elsewhere. Understanding the pathogenesis of these cysts will
      help target treatment to the joint, improve surgical outcomes, and decrease
      recurrences.

PMID- 20043772
TI  - Meralgia paresthetica secondary to lipoma.
AB  - Meralgia paresthetica (MP) consists of pain or dysthesia in the lateral thigh
      caused by entrapment of the lateral femoral cutaneous nerve (LFCN) underneath the
      inguinal ligament. The causes include iliac crest bone graft harvesting, seat
      belt injury associated with motor vehicle accident, diabetes mellitus, and
      trauma. The authors present the case of a 50-year-old woman who had a 1-year
      history of right-sided MP. The patient's history and the results of physical and
      radiological examinations were otherwise unremarkable except for the finding of a
      lipoma over the surface of the right sartorius muscle. Electrophysiological
      studies were interpreted as demonstrating peripheral neuropathy only.
      Conservative treatment, including heat or ice packing and local anesthetic and
      steroid injections, failed to control the patient's symptoms. Although sectioning
      or neurolysis of the LFCN appears to offer good-to-excellent results, the patient
      underwent excision of the lipoma. The symptoms resolved completely. To the best
      of the authors' knowledge this is the first case of MP associated with
      compression caused by a lipoma. The authors conclude that lipoma compression can
      cause MP, and in such cases, total excision of the lipoma may resolve the
      condition.

PMID- 20043773
TI  - Early functional outcomes and histological analysis after spinal cord compression
      injury in rats.
AB  - OBJECT: Neuroprotective and repair strategies in spinal cord injuries (SCIs) have
      been so far largely unsuccessful. One of the prerequisites is the use of
      appropriate preclinical models to decipher pathophysiological mechanisms; another
      is the identification of optimal time windows for therapeutic interventions. The
      authors undertook this study to characterize early motor, sensory, autonomic, and
      histological outcomes after balloon compression of the spinal cord at the T8-9
      level in adult rats. METHODS: A total of 91 rats were used in this study. Spinal
      cord balloon compression was performed at T8-9 in adult rats by inflation of a 2
      Fr Fogarty catheter into the epidural space. The authors first characterized
      early motor, sensory, and autonomic outcomes of 2 volumes of compression (10 and
      15 microl) using behavioral tests and then examined histological outcomes in the
      spinal cord using Luxol fast blue staining. To further substantiate the
      characterization of the epidural balloon-compression model, they used a
      noncompetitive N-methyl-D-aspartate antagonist, GK11, and demonstrated the
      involvement of excitotoxicity in this model. RESULTS: Proportional and
      reproducible functional impairment resulted from compression caused by balloon
      inflation with either 10 or 15 microl of water and corresponded to the extent of
      the lesion. Indeed, during the early phase following SCI (1 week postinjury),
      recovery of locomotor function and bladder control correlated with the volume of
      inflation, whereas outcomes with respect to sensory function and reflexes were
      independent of compression severity. Treatment with GK11 significantly improved
      motor function in all groups of rats 1 week after injury and bladder voiding in
      the 10-microl injured rats compared to the 15-microl injured rats. CONCLUSIONS:
      The results of this study demonstrate that spinal balloon-compression injury in
      the rat is a well-characterized, reproducible, and predictable model to analyze
      early events following SCI.

PMID- 20043775
TI  - Evaluation of a real-time, continuous monitor of glucose concentration in healthy
      dogs during anesthesia.
AB  - OBJECTIVE: To evaluate the accuracy of a real-time, continuous glucose monitoring
      system (CGMS) in healthy dogs undergoing anesthesia for elective
      ovariohysterectomy or orchiectomy. ANIMALS: 10 healthy dogs undergoing routine
      elective surgery. PROCEDURES: A CGMS was placed and used to obtain calculated
      glucose measurements before, during, and after anesthesia in each dog.
      Periodically, CGMS measurements were compared with concurrent measurements of
      glucose concentration in peripheral venous blood obtained with a portable
      chemistry analyzer (PCA). RESULTS: CGMS-calculated glucose measurements were
      significantly different from PCA blood glucose measurements during most of the
      anesthetic period. The CGMS values differed from PCA values by > 20% in 54 of 126
      (42.9%) paired measurements obtained during the anesthetic period. Hypoglycemia
      was evident in CGMS measurements 25 of 126 (19.8%) times during anesthesia. By
      comparison, only 1 incident of hypoglycemia was detected with the PCA during the
      same period. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the CGMS for routine
      monitoring of interstitial glucose concentration as an indicator of blood glucose
      concentration during anesthesia cannot be recommended. Additional investigation
      is necessary to elucidate the cause of discrepancy between CGMS results and PCA
      data during anesthesia.

PMID- 20043776
TI  - Evaluation of segmental dorsolumbar epidural analgesia with ketamine
      hydrochloride administered by use of nonstyletted multiple-port catheters via the
      caudal approach in cattle.
AB  - OBJECTIVE: To evaluate use of nonstyletted multiple-port catheters for epidural
      administration of ketamine hydrochloride via the caudal approach to induce
      analgesia of the paralumbar fossa (flank) in cattle. ANIMALS: 6 healthy bulls.
      PROCEDURES: 1 week before experiments began, a multiple-port catheter was
      inserted by use of a Tuohy needle in all cattle via the caudal approach (between
      the first and second coccygeal vertebrae); the tip was threaded approximately 48
      cm cranial into the dorsolumbar region. Each bull was administered ketamine (0.3,
      0.5, or 0.7 mg/kg) at time 0. Heart rate, blood pressures, respiratory rate,
      rectal temperature, analgesia, sedation, and ataxia were determined before
      treatment (baseline [time 0]); at 5, 10, 15, 30, 45, 60, 75, and 90 minutes; and
      every 30 minutes thereafter until end of analgesia. RESULTS: All multiple-port
      catheters were threaded with negligible resistance into the dorsolumbar region in
      all bulls. All doses of ketamine were effective for inducing analgesia of the
      flank region of bulls in a standing position. Total analgesia time was dose
      dependent (35, 50, and 80 minutes for 0.3, 0.5, and 0.7 mg/kg, respectively). All
      doses of ketamine induced mild or moderate ataxia. Heart rate changes were within
      acceptable limits. CONCLUSIONS AND CLINICAL RELEVANCE: Segmental dorsolumbar
      epidural analgesia with ketamine administered via multiple-port catheters by use
      of the caudal approach in cattle was feasible, and the cattle remained standing
      with minimal adverse effects. Further studies are necessary to determine whether
      this technique provides optimal conditions to allow surgery in standing cattle.

PMID- 20043777
TI  - Effects of hypercapnia, hypocapnia, and hyperoxemia on blood oxygenation level
      dependent signal intensity determined by use of susceptibility-weighted magnetic
      resonance imaging in isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To assess the effects of alterations in PaCO(2) and PaO(2) on blood
      oxygenation level-dependent (BOLD) signal intensity determined by use of
      susceptibility-weighted magnetic resonance imaging in brains of isoflurane
      anesthetized dogs. ANIMALS: 6 healthy dogs. PROCEDURES: In each dog, anesthesia
      was induced with propofol (6 to 8 mg/kg, IV) and maintained with isoflurane
      (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). During 1 magnetic resonance
      imaging session in each dog, targeted values of PaCO(2) (20, 40, or 80 mm Hg) and
      PaO(2) (100 or 500 mm Hg) were combined to establish 6 experimental conditions,
      including a control condition (PaCO(2), 40 mm Hg; PaO(2), 100 mm Hg). Dogs were
      randomly assigned to different sequences of conditions. Each condition was
      established for a period of >or= 5 minutes before susceptibility-weighted imaging
      was performed. Signal intensity was measured in 6 regions of interest in the
      brain, and data were analyzed by use of an ANCOVA and post hoc Tukey-Kramer
      adjustments. RESULTS: Compared with control condition findings, BOLD signal
      intensity did not differ significantly in any region of interest. However, signal
      intensities in the thalamus and diencephalic gray matter decreased significantly
      during both hypocapnic conditions, compared with all other conditions except for
      the control condition. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane
      anesthetized dogs, certain regions of gray matter appeared to have greater
      cerebrovascular responses to changes in PaCO(2) and PaO(2) than did others. Both
      PaO(2) and PaCO(2) should be controlled during magnetic resonance imaging
      procedures that involve BOLD signaling and taken into account when interpreting
      findings.

PMID- 20043778
TI  - Effect of exercise and osteochondral injury on synovial fluid and serum
      concentrations of carboxy-terminal telopeptide fragments of type II collagen in
      racehorses.
AB  - OBJECTIVE: To investigate the effects of exercise and osteochondral injury on
      concentrations of carboxy-terminal telopeptide fragments of type II collagen (CTX
      II) in synovial fluid (SF) and serum of Thoroughbred racehorses and to compare
      findings with radiographic and arthroscopic scores of joint injury severity.
      ANIMALS: 78 Thoroughbreds with (n = 38) and without (40) osteochondral injury.
      PROCEDURES: Serum and metacarpophalangeal or carpal joint SF samples were
      collected from noninjured horses before and at the end of 5 to 6 months of race
      training (pre- and postexercise samples, respectively) and from horses with
      osteochondral injury (1 joint assessed/horse). Synovial fluid and serum CTX-II
      concentrations were determined by use of an ELISA. Radiographic and arthroscopic
      scores of joint injury severity were determined for the injured horses. RESULTS:
      The CTX-II concentrations in SF and SF:serum CTX-II ratio were significantly
      higher for horses with joint injuries, compared with pre- and postexercise
      findings in noninjured horses. Serum CTX-II concentrations in postexercise and
      injured-horse samples were significantly lower than values in pre-exercise
      samples. On the basis of serum and SF CTX-II concentrations and SF:serum CTX-II
      ratio, 64% to 93% of serum and SF samples were correctly classified into their
      appropriate group (pre-exercise, postexercise, or injured-joint samples). In
      horses with joint injuries, arthroscopic scores were positively correlated with
      radiographic scores, but neither score correlated with SF or serum CTX-II
      concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that serum
      and SF CTX-II concentrations and SF:serum CTX-II ratio may be used to detect
      cartilage degradation in horses with joint injury.

PMID- 20043779
TI  - Comparison of bone mineral density in medial coronoid processes of dogs with and
      without medial coronoid process fragmentation.
AB  - OBJECTIVE: To quantify bone mineral density (BMD) in the medial coronoid process
      (MCP) of dogs with and without fragmented medial coronoid processes (FMCPs) by
      use of dualenergy x-ray absorptiometry. SAMPLE POPULATION: 50 osteochondral
      samples from 31 dogs that underwent subtotal coronoid ostectomy for unilateral or
      bilateral FMCP and 10 control osteochondral samples of the MCP collected from
      forelimbs of 5 cadaveric Greyhounds. PROCEDURES: Each sample was mounted in
      proximodistal and mediolateral orientations for BMD determinations via dual
      energy x-ray absorptiometry, and area-of-interest data (0.03-cm(2) increments)
      were obtained. Values of BMD were compared between left and right limb control
      samples, between control and FMCP samples, and between axial and abaxial regions
      of the control or FMCP samples. RESULTS: The BMD in control and FMCP samples in
      both proximodistal and mediolateral orientations differed significantly. Mean BMD
      throughout the MCP was decreased in FMCP samples, compared with control sample
      findings. In both control and FMCP samples, BMD of the abaxial half of the MCP
      was 50% higher than that of the axial portion. CONCLUSIONS AND CLINICAL
      RELEVANCE: The similar pattern of BMD in osteochondral samples of the MCP in dogs
      with and without FMCP indicated that the MCP was eccentrically loaded during
      weight bearing. Topographic variation in BMD in the MCP, and hence tolerance to
      compressive loading, suggested that the abaxial portion of the MCP in dogs was
      more resistant to compressive load than was the axial edge. This difference may
      predispose the coronoid process to microcrack formation and fragmentation at that
      juxtaposition.

PMID- 20043780
TI  - Association between clinical signs and histopathologic changes in the synovium of
      the tarsocrural joint of horses with osteochondritis dissecans of the tibia.
AB  - OBJECTIVE: To develop a scoring system for histopathologic changes in the
      synovium of tarsocrural joints (TCJs) of horses with osteochondritis dissecans
      (OCD) and to test for association between histopathologic changes and joint
      effusion or lameness. ANIMALS: 93 horses with OCD of the intermediate ridge of
      the tibia of 1 or both TCJs (134 joints) and 38 control horses without disease of
      TCJs (38 joints). PROCEDURES: For OCD-affected horses, pretreatment lameness, TCJ
      effusion, and results of pelvic limb flexion test were scored. Synovial biopsy
      specimens were obtained from TCJs of OCD-affected horses during arthroscopy, and
      similar postmortem tissue specimens were obtained from control horses through a
      small arthrotomy. Histologic signs of synovitis in 172 biopsy specimens were
      scored by 2 pathologists (A and B) by use of 2 criteria: synoviocyte
      proliferation and cellular infiltration. RESULTS: Analysis of scoring revealed
      good to very good intraobserver agreement within pathologist A (weighted kappa
      [WK], 0.76 to 0.81), and moderate to good agreement within pathologist B (WK,
      0.56 to 0.63). Interobserver agreement for synoviocyte proliferation (WK, 0.34 to
      0.52) and cellular infiltration (WK, 0.38 to 0.48) scores was fair to moderate.
      Joint effusion and synoviocyte proliferation were significantly associated, as
      were joint effusion and cellular infiltration. There was no association between
      histopathologic changes and the other clinical signs evaluated. CONCLUSIONS AND
      CLINICAL RELEVANCE: The scoring system was helpful for evaluating synovial
      inflammation caused by OCD of the intermediate ridge of the tibia in horses.
      Histopathologic signs of synovial inflammation were associated with effusion but
      not with lameness.

PMID- 20043781
TI  - Measurement of plasma cardiac troponin I concentration by use of a point-of-care
      analyzer in clinically normal horses and horses with experimentally induced
      cardiac disease.
AB  - OBJECTIVE: To compare cardiac troponin I (cTnI) concentrations determined by use
      of a point-of-care analyzer with values determined by use of a bench-top
      immunoassay in plasma samples obtained from clinically normal horses with and
      without experimentally induced cardiac disease, and to establish a reference
      range for plasma equine cTnI concentration determined by use of the point-of-care
      analyzer. ANIMALS: 83 clinically normal horses, 6 of which were administered
      monensin to induce cardiac disease. PROCEDURES: A blood sample was collected from
      each of the 83 clinically normal horses to provide plasma for analysis by use of
      the point-of-care analyzer; some of the same samples were also analyzed by use of
      the immunoassay. All 83 samples were used to establish an analyzer-specific
      reference range for plasma cTnI concentration in clinically normal horses. In 6
      horses, blood samples were also collected at various time points after
      administration of a single dose of monensin (1.0 to 1.5 mg/kg) via nasogastric
      intubation; plasma cTnI concentration in those samples was assessed by use of
      both methods. RESULTS: The analyzer-specific reference range for plasma cTnI
      concentration in clinically normal horses was 0.0 to 0.06 ng/mL. Following
      monensin treatment in 5 horses, increases in plasma cTnI concentration determined
      by use of the 2 methods were highly correlated (Pearson correlation, 0.83). Peak
      analyzer-determined plasma cTnI concentrations in monensin-treated horses ranged
      from 0.08 to 3.68 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with and
      without experimentally induced cardiac disease, the point-of-care analyzer and
      bench-top immunoassay provided similar values of plasma cTnI concentration.

PMID- 20043782
TI  - Effects of pretreatment with dexamethasone or levothyroxine sodium on endotoxin
      induced alterations in glucose and insulin dynamics in horses.
AB  - OBJECTIVE: To investigate the effects of dexamethasone or levothyroxine sodium on
      endotoxin-induced alterations in glucose and insulin dynamics. ANIMALS: 24
      horses. PROCEDURES: Horses were randomly allocated to 3 treatment groups and
      received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone
      plus oats, or oats alone (control) for 15 days, followed by IV infusion of
      lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently
      sampled IV glucose tolerance tests were performed prior to pretreatment, after
      pretreatment, and 20 hours after lipopolysaccharide administration. Area under
      the curve for plasma glucose and serum insulin concentrations was calculated, and
      minimal model analyses were performed. RESULTS: Significant treatment-by-time
      effects were detected for insulin sensitivity (SI) and area under the curve for
      glucose and insulin in the 15-day pretreatment period. Insulin sensitivity
      significantly decreased over time in all treatment groups, with the largest
      decrease detected in the dexamethasone group. Administration of
      lipopolysaccharide further decreased mean SI by 71% and 63% in the dexamethasone
      and control groups, respectively, but did not affect horses in the levothyroxine
      group. Mean SI was the lowest in the dexamethasone group, but percentage
      reduction was the same for dexamethasone and control groups. CONCLUSIONS AND
      CLINICAL RELEVANCE: Insulin sensitivity decreased during the pretreatment period
      in all 3 groups, indicating that hospitalization affected glucose and insulin
      dynamics. Dexamethasone significantly lowered SI, and endotoxemia further
      exacerbated insulin resistance. In contrast, there was no additional effect of
      endotoxemia on SI in horses pretreated with levothyroxine, suggesting that this
      treatment prevented endotoxemia-induced insulin resistance.

PMID- 20043785
TI  - Assessment of reproductive tract disease in cats at risk for Tritrichomonas
      foetus infection.
AB  - OBJECTIVE: To determine whether Tritrichomonas foetus infection resides in
      reproductive tract tissues from cats housed for breeding and for which a high
      prevalence of colonic T foetus infection has been reported. ANIMALS: 61 purebred
      cats in 36 catteries undergoing elective ovariohysterectomy or castration and for
      which reproductive tract tissues, feces, and a reproductive history were
      obtained. PROCEDURES: Reproductive tract tissues were examined for T foetus via
      light microscopy, immunohistochemical analysis, and PCR assay. History of
      reproductive tract disease was examined to detect statistical associations with
      identified or reported exposure to colonic T foetus infection. RESULTS: 15 of 61
      (25%) cats and 22 of 33 (67%) catteries were identified with active or reported T
      foetus infection. Light microscopic, immunohistochemical, or molecular evidence
      of T foetus infection of the reproductive tract was not detected in any cats,
      including 15 cats with colonic T foetus infection, 29 cats residing in a cattery
      in which T foetus-infected cats were identified, and 8 cats for which gross or
      light microscopic evidence of reproductive tract disease was identified. There
      were no differences in total number of litters, number of litters per breeding,
      kitten mortality rate, or birth defects between cats or catteries infected with T
      foetus and those for which T foetus infection was not identified. CONCLUSIONS AND
      CLINICAL RELEVANCE: No evidence of reproductive tract colonization by T foetus
      was detected in this study. Accordingly, it is unlikely that reproductive tract
      infection with T foetus plays an important role in overall disease transmission.

PMID- 20043783
TI  - Anti-inflammatory effects of intra-articular administration of morphine in horses
      with experimentally induced synovitis.
AB  - OBJECTIVE: To compare the effects of intra-articular (IA) versus IV
      administration of morphine on local and systemic inflammatory responses in horses
      with experimentally induced acute synovitis. ANIMALS: 8 horses. PROCEDURES: Each
      horse received the following 2 treatments 4 hours after synovitis was induced: IA
      administration of morphine (0.05 mg/kg) with IV administration of 1 mL of saline
      (0.9% NaCl) solution/100 kg, and IA administration of 1 mL of saline solution/100
      kg with IV administration of morphine (0.05 mg/kg). Treatments were administered
      in randomized order with a washout period of 3 weeks between treatments. Before
      each treatment, aseptic synovitis was induced by injection of lipopolysaccharide
      into a radiocarpal joint. For the second treatment, the contralateral radiocarpal
      joint was selected. Joint swelling and skin temperature over the treated joints
      were recorded. Clinical examinations were performed, and blood WBC count, serum
      amyloid A (SAA) concentration, serum cortisol concentration, synovial fluid WBC
      count, synovial fluid total protein (TP) concentration, and synovial fluid SAA
      concentration were measured before and repeatedly during each of the two 168-hour
      study periods. Data were analyzed by use of ANOVA with repeated measures.
      RESULTS: IA administration of morphine resulted in significantly less joint
      swelling and lower synovial fluid TP and serum and synovial fluid SAA
      concentrations, and blood WBC count than did IV administration of morphine.
      CONCLUSIONS AND CLINICAL RELEVANCE: IA administration of morphine exerted anti
      inflammatory properties in horses with experimentally induced acute synovitis,
      supporting its use as a part of a balanced analgesic protocol.

PMID- 20043786
TI  - Potential impact of introduction of foot-and-mouth disease from wild pigs into
      commercial livestock premises in California.
AB  - OBJECTIVE: To estimate potential spread of foot-and-mouth disease (FMD) if
      introduced from wild pigs in California and to evaluate efficacies of various
      control strategies. SAMPLE POPULATION: Data for California livestock and from
      hunter surveys on wild pigs in California. PROCEDURES: A spatial, stochastic
      simulation model was used to simulate FMD epidemics that might occur if a dairy
      or beef herd were infected from contact with a wild pig. Index herd location and
      type were examined, in addition to different statewide movement ban (SWMB)
      durations, to determine their effect on extent of the epidemic. RESULTS:
      Duration, number of infected premises, size of simulated outbreak, number of
      culled animals, and spatial distribution of infected herds resulting from the
      simulated outbreaks varied considerably among geographic regions, depending on
      index case type and location. Outbreaks beginning in the southern region of
      California were consistently longest, whereas those beginning in the northern
      region were shortest. The largest outbreaks resulted from index cases located in
      the southern and valley regions, whereas outbreaks were smallest when originating
      in the Sonoma or northern regions. For all regions, when the index herd was a
      dairy herd, size and duration of the outbreak were consistently reduced with
      implementation of an SWMB >or= 3 days. CONCLUSIONS AND CLINICAL RELEVANCE:
      Introduction of FMDV from wild pigs into a dairy or beef herd could result in a
      large and rapidly spreading outbreak, potentially affecting large numbers of
      herds. Size and duration of the outbreak might be reduced with an SWMB; however,
      the impact is highly dependent on the index herd type and location.

PMID- 20043787
TI  - Evaluation of the protective effects of all-trans-astaxanthin on canine
      osteosarcoma cell lines.
AB  - OBJECTIVE: To determine the effects of the antioxidant astaxanthin on growth of
      canine osteosarcoma cells with and without concurrent chemotherapeutic or
      irradiation insult. SAMPLE POPULATION: Cells from 3 established canine
      osteosarcoma cell lines (D17, OS 2.4, and HMPOS). PROCEDURES: Growth-curve
      kinetics and cell cytotoxic effects were assessed by means of various treatment
      combinations and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. Western blotting was performed to examine previously identified signaling
      pathways that astaxanthin reportedly affects. Additionally, cell-cycle kinetic
      evaluations, soft agar colony-forming assays, and antioxidant assays were
      performed to better understand the effect of astaxanthin on cell growth and
      function. RESULTS: Exposure to astaxanthin alone resulted in a mild to pronounced
      attenuation of cell proliferation in vitro, depending on the cell line, and did
      not interfere with the cell-death response to doxorubicin, irradiation, or
      peroxide-mediated insult. In some instances, astaxanthin acted in an additive
      fashion to augment cell death. Astaxanthin exposure increased the antioxidant
      potential of cells, whereas peroxide-mediated cell stress increased the
      antioxidant potential to the same degree as astaxanthin exposure or greater. No
      dramatic changes in phosphorylation of protein kinase B or upregulation of
      connexin 43 were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested
      that astaxanthin administration may be beneficial in treatment of dogs for
      osteosarcoma. Its actions as an antioxidant did not improve osteosarcoma cell
      survival during chemotherapeutic or irradiation insults, warranting further
      research into this natural compound as an adjuvant, antiproliferative treatment
      for osteosarcoma in dogs.

PMID- 20043788
TI  - Evaluation of a behavioral method for objective vision testing and identification
      of achromatopsia in dogs.
AB  - OBJECTIVE: To develop a quantifiable behavioral test for identification of
      achromatopsic dogs based on visual performance. ANIMALS: 14 dogs. PROCEDURES: A
      3.6-m-long obstacle-avoidance course with 6 obstacle panels was developed from a
      preliminary 2.4-m-long course. Achromatopsic and visually normal control dogs
      were run through the course at 4 ambient light intensities (from dim to bright:
      0.2, 25, 65, and 646 lux). Completion of 4 runs ranging from dimmest to brightest
      light intensity constituted 1 complete trial. Each dog underwent 3 trials.
      Transit times were measured and compared between dog groups and between light
      intensities by use of a generalized linear model and ANOVA. RESULTS: At the 3
      highest light intensities, the achromatopsic dogs needed significantly more time
      to pass through the obstacle course than the control animals. Compared with the
      mean transit time at the lowest light intensity, mean transit times were 2.6
      times as long at 25 lux, 3.2 times as long at 65 lux, and 5.7 times as long at
      646 lux. The achromatopsic dogs had signs of increasing difficulty navigating
      around the obstacle panels with increasing light intensities; this was not the
      situation for the control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: A 3.6-m-long
      obstacle-avoidance course with 6 movable obstacle panels allowed identification
      of achromatopsic dogs at ambient light intensities >or= 25 lux based on transit
      times. This test could be helpful in the evaluation of new cone photoreceptor
      specific treatments.

PMID- 20043790
TI  - Evaluation of the safety of spinosad and milbemycin 5-oxime orally administered
      to Collies with the MDR1 gene mutation.
AB  - OBJECTIVE: To determine whether signs of avermectin (AVM)-milbemycin (MB)
      toxicosis would be evident in AVM-MB-sensitive Collies after treatment with an
      experimental formulation of spinosad alone or spinosad combined with MB 5-oxime
      (MBO) at doses up to 5 and 10 times the MBO maximum label dose. ANIMALS: 20 adult
      Collies homozygous or heterozygous for the MDR1 gene mutation that had signs of
      toxicosis after oral administration of ivermectin. PROCEDURES: On the basis of
      AVM-MB sensitivity score, each dog was assigned in a randomized block design to 1
      of 5 treatment groups (control group, 300 mg of spinosad/kg [5 times maximum
      label dose], 180 mg of spinosad/kg with 3 mg of MBO/kg [3 times maximum MBO label
      dose], 300 mg of spinosad/kg with 5 mg of MBO/kg, and 300 mg of spinosad/kg with
      10 mg of MBO/kg). Treatments were administered orally as a sequence of single
      doses during 5 consecutive days. After a 28-day washout period, treatment
      sequences were repeated. Posttreatment observation and scoring by blinded
      observers were conducted to specifically include neurologic abnormalities typical
      of AVM-MB toxicosis, such as signs of depression, ataxia, mydriasis, and
      hypersalivation. RESULTS: No signs of AVM-MB toxicosis were attributed to
      treatment in any dog during the study. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that oral administration of spinosad at 300 mg/kg alone or in
      combination with MBO at doses up to 10 mg/kg did not cause signs of AVM-MB
      toxicosis in AVM-MB-sensitive dogs with the MDR1 gene mutation.

PMID- 20043789
TI  - Evaluation of early cellular influences of bone morphogenetic proteins 12 and 2
      on equine superficial digital flexor tenocytes and bone marrow-derived
      mesenchymal stem cells in vitro.
AB  - OBJECTIVE: To evaluate early cellular influences of bone morphogenetic protein
      (BMP)12 and BMP2 on equine superficial digital flexor tenocytes (SDFTNs) and
      equine bone marrow-derived mesenchymal stem cells (BMDMSCs). ANIMALS: 9 adult
      clinically normal horses. PROCEDURES: BMDMSCs and SDFTNs were cultured in
      monolayer, either untreated or transduced with adenovirus encoding green
      fluorescent protein, adenovirus encoding BMP12, or adenovirus encoding BMP2.
      Cytomorphologic, cytochemical, immunocytochemical, and reverse transcriptase
      quantitative PCR (RT-qPCR) analyses were performed on days 3 and 6. Genetic
      profiling for effects of BMP12 was evaluated by use of an equine gene expression
      microarray on day 6. RESULTS: BMDMSCs and SDFTNs had high BMP12 gene expression
      and remained viable and healthy for at least 6 days. Type l collagen
      immunocytochemical staining for SDFTNs and tenocyte-like morphology for SDFTNs
      and BMDMSCs were greatest in BMP12 cells. Cartilage oligomeric matrix protein, as
      determined via RT-qPCR assay, and chondroitin sulfate, as determined via gene
      expression microarray analysis, were upregulated relative to control groups in
      SDFTN-BMP12 cells. The BMDMSCs and SDFTNs became mineralized with BMP2, but not
      BMP12. Superficial digital flexor tenocytes responded to BMP12 with upregulation
      of genes relevant to tendon healing and without mineralization as seen with BMP2.
      CONCLUSIONS AND CLINICAL RELEVANCE: Targeted equine SDFTNs may respond to BMP12
      with improved tenocyte morphology and without mineralization, as seen with BMP2.
      Bone marrow-derived mesenchymal stem cells may be able to serve as a cell
      delivery method for BMP12.

PMID- 20043791
TI  - Effect of changes in number of doses and anatomic location for administration of
      an Escherichia coli bacterin on serum IgG1 and IgG2 concentrations in dairy cows.
AB  - OBJECTIVE: To determine effects of injection site on antibody response to J5
      Escherichia coli bacterin. ANIMALS: 28 adult Holstein cows. PROCEDURES: Cows were
      randomly assigned as control cattle (n = 4 cows), not administered J5 E coli
      bacterin; 3X (8), administered 3 doses of bacterin SC in the left side of the
      neck; 5XN (8), administered 5 doses of bacterin SC in the left side of the neck;
      or 5XSR (8), administered 5 doses of bacterin SC sequentially in the left side of
      the neck, right side of the neck, right side of the thorax, left side of the
      thorax, and left side of the neck. Blood samples were collected from the cows to
      determine anti-J5 E coli IgG1 and IgG2 concentrations. RESULTS: Vaccinated cows
      had higher mean serum anti-J5 E coli IgG1 concentrations than did control cows.
      The 5XN and 5XSR cows had higher mean serum anti-J5 E coli IgG1 concentrations
      than did 3X cows. Additionally, 5XSR cows had higher mean serum anti-J5 E coli
      IgG1 concentrations than did 5XN cows. Vaccinated cows had higher mean serum anti
      J5 E coli IgG2 concentrations than did control cows. The 5XN and 5XSR cows had
      higher mean serum anti-J5 E coli IgG2 concentrations than did 3X cows. The 5XSR
      cows had higher mean serum anti-J5 E coli IgG2 concentrations than did all other
      groups at 84 days after the fifth vaccination. CONCLUSIONS AND CLINICAL
      RELEVANCE: Sequential doses of core-antigen bacterins administered at different
      anatomic locations may improve antibody response in dairy cattle.

PMID- 20043793
TI  - AVMA to seek congressional resolution honoring veterinary anniversary.

PMID- 20043794
TI  - What is your diagnosis? Abscess.

PMID- 20043795
TI  - What is your diagnosis? Unilateral congential ankylosis.

PMID- 20043796
TI  - Diagnostic imaging in veterinary dental practice. Endodontic disease.

PMID- 20043797
TI  - Pathology in practice. Enteritis.

PMID- 20043798
TI  - ECG of the Month. Atrial flutter.

PMID- 20043799
TI  - What is the evidence? How accurate are noninvasive transmission pulse oximeters
      in dogs?

PMID- 20043800
TI  - Multicenter veterinary practice assessment of the effects of omega-3 fatty acids
      on osteoarthritis in dogs.
AB  - OBJECTIVE: To assess the effect of food containing high concentrations of fish
      oil omega-3 fatty acids and a low omega-6-omega-3 fatty acid ratio on clinical
      signs of osteoarthritis in dogs. DESIGN: Randomized, double-blinded, controlled
      clinical trial. ANIMALS: 127 client-owned dogs with osteoarthritis in 1 or more
      joints from 18 privately owned veterinary clinics. PROCEDURES: Dogs were randomly
      assigned to be fed for 6 months with a typical commercial food or a test food
      containing a 31-fold increase in total omega-3 fatty acid content and a 34-fold
      decrease in omega-6-omega-3 ratio, compared with the control food. Dog owners
      completed a questionnaire about their dog's arthritic condition, and
      investigators performed a physical examination and collected samples for a CBC
      and serum biochemical analyses (including measurement of fatty acids
      concentration) at the onset of the study and at 6, 12, and 24 weeks afterward.
      RESULTS: Dogs fed the test food had a significantly higher serum concentration of
      total omega-3 fatty acids and a significantly lower serum concentration of
      arachidonic acid at 6, 12, and 24 weeks. According to owners, dogs fed the test
      food had a significantly improved ability to rise from a resting position and
      play at 6 weeks and improved ability to walk at 12 and 24 weeks, compared with
      control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Ingestion of the test food
      raised blood concentrations of omega-3 fatty acids and appeared to improve the
      arthritic condition in pet dogs with osteoarthritis.

PMID- 20043803
TI  - Evaluation of calorie density and feeding directions for commercially available
      diets designed for weight loss in dogs and cats.
AB  - OBJECTIVE: To determine range of calorie density and feeding directions for
      commercially available diets designed for weight management in dogs and cats.
      DESIGN: Cross-sectional study. SAMPLE POPULATION: 93 diets (44 canine diets and
      49 feline diets) that had a weight management claim with feeding directions for
      weight loss or implied weight management claims. PROCEDURES: Calorie density was
      collected from product labels or by contacting manufacturers. Recommended feeding
      directions for weight loss were compared with resting energy requirement (RER)
      for current body weight by use of a standard body weight (36.4 kg [80 lb] for
      canine diets and 5.5 kg [12 lb] for feline diets). RESULTS: Calorie density for
      the 44 canine diets ranged from 217 to 440 kcal/cup (median, 301 kcal/cup) and
      from 189 to 398 kcal/can (median, 310 kcal/can) for dry and canned diets,
      respectively. Calorie density for the 49 feline diets ranged from 235 to 480
      kcal/cup (median, 342 kcal/cup) and from 78 to 172 kcal/can (median, 146
      kcal/can) for dry and canned diets, respectively. Recommended calorie intake for
      weight loss in dogs ranged from 0.73 to 1.47 x RER (median, 1.00 x RER) and for
      weight loss in cats ranged from 0.67 to 1.55 x RER (median, 1.00 x RER). Diets
      ranged from $0.04 to $1.11/100 kcal of diet (median, $0.15/100 kcal of diet).
      CONCLUSIONS AND CLINICAL RELEVANCE: Wide variation existed in recommended calorie
      intake, kilocalories, and cost for diets marketed for weight loss in pets. This
      variability could contribute to challenges of achieving successful weight loss in
      pets.

PMID- 20043801
TI  - Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty
      acids on weight bearing in dogs with osteoarthritis.
AB  - OBJECTIVE: To evaluate the effects of a food supplemented with fish oil omega-3
      fatty acids on weight bearing in dogs with osteoarthritis. DESIGN: Randomized,
      double-blinded, controlled clinical trial. ANIMALS: 38 client-owned dogs with
      osteoarthritis examined at 2 university veterinary clinics. PROCEDURES: Dogs were
      randomly assigned to receive a typical commercial food (n = 16) or a test food
      (22) containing 3.5% fish oil omega-3 fatty acids. On day 0 (before the trial
      began) and days 45 and 90 after the trial began, investigators conducted
      orthopedic evaluations and force-plate analyses of the most severely affected
      limb of each dog, and owners completed questionnaires to characterize their dogs'
      arthritis signs. RESULTS: The change in mean peak vertical force between days 90
      and 0 was significant for the test-food group (5.6%) but not for the control-food
      group (0.4%). Improvement in peak vertical force values was evident in 82% of the
      dogs in the test-food group, compared with 38% of the dogs in the control-food
      group. In addition, according to investigators' subjective evaluations, dogs fed
      the test food had significant improvements in lameness and weight bearing on day
      90, compared with measurements obtained on day 0. CONCLUSIONS AND CLINICAL
      RELEVANCE: At least in the short term, dietary supplementation with fish oil
      omega-3 fatty acids resulted in an improvement in weight bearing in dogs with
      osteoarthritis.

PMID- 20043804
TI  - Evaluation of the diagnostic value of an implantable loop recorder in dogs with
      unexplained syncope.
AB  - OBJECTIVE: To evaluate the diagnostic value of an implantable loop recorder (ILR)
      in dogs with unexplained syncope. DESIGN: Prospective case series. ANIMALS: 12
      dogs with recurrent unexplained syncope. PROCEDURES: An ILR was surgically
      inserted in a pocket created in the subcutaneous tissues of the left hemithorax
      of each dog. The ILRs were programmed for manual and automatic activation, and
      event analysis and programming were performed at 3-month intervals and after each
      syncopal episode. RESULTS: The ILR was manually activated in 7 of 12 dogs at
      least once within 45 to 218 days (median, 120 days) after implantation. Four dogs
      had syncopal episodes associated with sinus tachycardia followed by sinus
      bradycardia and asystolic pauses. Two dogs had ventricular tachycardia, and 1 dog
      had sinus node dysfunction with prolonged sinus arrest that coincided with loss
      of consciousness and falling. Four dogs had no additional syncopal episodes after
      implantation of the ILR. In the remaining dog, the owner was unable to activate
      the ILR during the only syncopal episode observed for that dog after ILR
      implantation. In all 12 dogs, analysis of ECG traces after automatic activation
      of recording revealed normal cardiac rhythms. CONCLUSIONS AND CLINICAL RELEVANCE:
      Data gained after manual activation of an ILR provided valuable diagnostic and
      prognostic information in almost all dogs with unexplained syncopal episodes by
      confirming or disproving an association between syncope and arrhythmias. However,
      detection of disturbances in cardiac rhythm after automatic activation did not
      appear to improve the diagnostic value for an ILR implanted in dogs.

PMID- 20043806
TI  - Association between outcome and organ system dysfunction in dogs with sepsis: 114
      cases (2003-2007).
AB  - OBJECTIVE: To determine whether multiple organ dysfunction syndrome (MODS) could
      be identified in dogs with sepsis secondary to gastrointestinal tract leakage,
      and whether the number of affected organ systems was significantly associated
      with mortality rate. DESIGN: Multicenter retrospective case series. ANIMALS: 114
      dogs. PROCEDURES: Medical records for dogs treated surgically because of sepsis
      secondary to gastrointestinal tract leakage between 2003 and 2007 were reviewed.
      Sepsis was diagnosed on the basis of results of bacterial culture of peritoneal
      fluid, gross evidence of gastrointestinal tract leakage at surgery, or both.
      Renal dysfunction was defined as a > or = 0.5 mg/dL increase in serum creatinine
      concentration after surgery. Cardiovascular dysfunction was defined as
      hypotension requiring vasopressor treatment. Respiratory dysfunction was defined
      as a need for supplemental oxygen administration or mechanical ventilation.
      Hepatic dysfunction was defined as a serum bilirubin concentration > 0.5 mg/dL.
      Dysfunction of coagulation was defined as prolonged prothrombin time, prolonged
      partial thromboplastin time, or platelet count < or = 100,000/microL. RESULTS: 89
      (78%) dogs had dysfunction of 1 or more organ systems, and 57 (50%) dogs had
      MODS. Mortality rate increased as the number of dysfunctional organ systems
      increased. Mortality rate was 70% (40/57) for dogs with MODS and 25% (14/57) for
      dogs without. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that MODS,
      defined as dysfunction of at least 2 organ systems, can be identified in dogs
      with sepsis and that organ system dysfunction increased the odds of death.

PMID- 20043807
TI  - Risk factors for surgical site infection-inflammation in dogs undergoing surgery
      for rupture of the cranial cruciate ligament: 902 cases (2005-2006).
AB  - OBJECTIVE: To evaluate the incidence of and potential risk factors associated
      with development of postoperative infection-inflammation in a large number of
      dogs with rupture of the cranial cruciate ligament (CCL) that were treated via
      elective surgery. DESIGN: Retrospective case series. ANIMALS: 808 dogs that
      underwent surgery (902 procedures) for rupture of the CCL. PROCEDURES: Medical
      records of dogs that underwent extracapsular lateral suture (ECLS) stabilization
      or tibial plateau leveling osteotomy (TPLO) between January 1, 2005, and December
      31, 2006, were reviewed. Data regarding development of postoperative infection
      inflammation were obtained. Potential risk factors were identified and recorded.
      RESULTS: 496 ECLS surgeries were performed, and 406 TPLO surgeries were
      performed. Infection-inflammation developed in 55 of 902 (6.1%) surgeries within
      6 months after surgery. There was a significant difference in infection
      inflammation rate after the ECLS surgeries (21/496 [4.2%]), compared with rate
      after the TPLO surgeries (34/406 [8.4%]). Factors associated with a significantly
      lower rate of infection-inflammation included the use of suture material other
      than stainless-steel staples for skin closure and postoperative oral
      administration of antimicrobials. CONCLUSIONS AND CLINICAL RELEVANCE: TPLO was
      associated with a significantly higher rate of infection-inflammation than the
      infection-inflammation rate after ECLS stabilization. The use of suture material
      other than staples for skin closure and postoperative oral administration of
      antimicrobials may be protective in minimizing infection-inflammation in dogs
      with rupture of the CCL that are treated via ECLS or TPLO.

PMID- 20043808
TI  - Modulation of amyloid beta peptide(1-42) cytotoxicity and aggregation in vitro by
      glucose and chondroitin sulfate.
AB  - One mechanism leading to neurodegeneration during Alzheimer's disease (AD) is
      amyloid beta peptide (Abeta)-induced neurotoxicity. Among the factors proposed to
      potentiate Abeta toxicity is its covalent modification through carbohydrate
      derived advanced glycation endproducts (AGEs). Other experimental evidence,
      though, indicates that certain polymeric carbohydrates like the glycosaminoglycan
      (GAG) chains found in proteoglycan molecules attenuate the neurotoxic effect of
      Abeta in primary neuronal cultures. Pretreatment of the 42-residue Abeta fragment
      (Abeta1-42) with the ubiquitous brain carbohydrates, glucose, fructose, and the
      GAG chondroitin sulfate B (CSB) inhibits Abeta1-42-induced apoptosis and reduces
      the peptide neurotoxicity on neuroblastoma cells, a cytoprotective effect that is
      partially reverted by AGE inhibitors such as pyridoxamine and L-carnosine.
      Thioflavin T fluorescence measurements indicate that at concentrations close to
      physiological, only CSB promotes the formation of Abeta amyloid fibril structure.
      Atomic force microscopy imaging and Western blot analysis suggest that glucose
      favours the formation of globular oligomeric structures derived from aggregated
      species. Our data suggest that at short times carbohydrates reduce Abeta1-42
      toxicity through different mechanisms both dependent and independent of AGE
      formation.

PMID- 20043809
TI  - Effect of synthetic cannabinoid HU210 on memory deficits and neuropathology in
      Alzheimer's disease mouse model.
AB  - Cannabinoids have been shown to increase neurogenesis in adult brain, as well as
      protect neurons from excitotoxicity, calcium influx, inflammation, and ischemia.
      Recent studies have shown that synthetic cannabinoids can alleviate water maze
      impairments in rats treated with intracranial amyloid beta protein (Abeta);
      however it is unknown whether this effect is due to the cannabinoids' anti
      inflammatory properties or whether it affects Abeta processing. Here we
      investigate whether cannabinoids have any effect on Alzheimer's disease in vivo.
      We found that HU210, a potent synthetic cannabinoid, did not improve water maze
      performance or a contextual fear conditioning task in an APP23/PS45 double
      transgenic mouse model of AD. HU210 had no effect on APP processing and Abeta
      generation, as well as neuritic plaque formation in the brains of AD transgenic
      mice. Our study showed that synthetic cannabinoid HU210 had no beneficial effects
      on AD neuropathology and behavioral deficits of AD model mice, which advises
      caution of such drug's application in AD therapies.

PMID- 20043810
TI  - Amyloid beta oligomers decrease hippocampal spontaneous network activity in an
      age-dependent manner.
AB  - Soluble amyloid beta (Abeta) oligomers might trigger early cognitive impairment
      in Alzheimer's Disease (AD) through the impairment of proper neuronal network
      function. We have recently shown that the short sequence Abeta(25-35) affects the
      spontaneous activity in hippocampal slices, when was added to the bath, at high
      nanomolar concentrations. In the present study, we aimed to characterize the
      effects of the oligomerized full length sequence Abeta(1-42) on the spontaneous
      network activity in the CA1 hippocampal area testing whether such effects are age
      dependent. By performing extracellular field recordings of spontaneous network
      activity of hippocampal slices, we found that an oligomerized solution of Abeta(1
      42) (osAbeta) potently inhibit, in a dose-dependent manner, the spontaneous
      hippocampal network activity with an IC(50) of 0.4 +/- 3.2 nM and a maximal
      effect reached around 10 nM. While spontaneous hippocampal network activity is
      unaffected by age, the sensitivity of spontaneous hippocampal network activity to
      osAbeta (10 nM) appears to be increased in slices from older animals. Moreover,
      to see a significant reduction in spontaneous network activity in slices from
      animals in their second week of life 100nM osAbeta was needed. The osAbeta
      induced reduction in hippocampal network activity is accompanied by a presynaptic
      reduction in both spontaneous and miniature synaptic potentials. Finally, we
      demonstrated that the effect produced by osAbeta on spontaneous network activity
      was specific, reversible and unrelated with cell death. In conclusion, our data
      show that osAbeta alters hippocampal network activity at concentrations commonly
      observed in AD patients and that such effect of osAbeta increase with age.

PMID- 20043811
TI  - The serum protein and lipid oxidation marker levels in Alzheimer's disease and
      effects of cholinesterase inhibitors and antipsychotic drugs therapy.
AB  - Oxidative stress plays an important role in the pathogenesis of Alzheimer's
      disease (AD). The aim of this study was to evaluate the serum oxidation marker
      levels in patients with AD. Both untreated patients (n: 15) and patients who
      received treatment (n: 62) had higher Malondialdehyde (p<0.01 and p<0.001),
      Oxidized LDL (ox-LDL; p<0.0001 and p<0.0001), F(2)-isoprostane (p<0.0001 and
      p<0.001), and Nitric oxide (NOx; p<0.0001 and p<0.0001) levels compared with
      those of age-matched controls (n: 15). Protein Carbonyl and Asymmetrical Dimethyl
      L-Arginine levels in Alzheimer patients were not found to be different from the
      controls. Short-term cholinesterase inhibitor (ChEIs) therapy (7, 5 +/-1, 5
      months, n: 12) resulted in a reduction in ox-LDL and NOx levels (p<0.05 and
      p<0.01) from baseline. Long-term ChEI- therapy group (50, 4+/- 30, 5 months, n:
      33) has higher ox-LDL, NOx and F(2)-isoprostane levels than short-term treated
      group (p<0.01, p<0.001 and p<0.05, respectively). Ox-LDL levels were also found
      to be lower in ChEI patients who were given antipsychotic treatment (n: 15) than
      in the group who were ChEIs-alone treatment group (p<0.0001). MMSE scores showed
      negative correlation with both NOx (p<0.05) and ox-LDL (p<0.05) levels. There was
      positive correlation between NOx and both MDA (p<0.05) and ox-LDL (p<0.05), and
      between F(2)-isoprostane and 3-NT (p<0.05). In conclusion, our results suggest
      that serum NOx-induced lipid oxidation levels were increased in AD and use of
      antipsychotic drugs may cause lower ox-LDL levels in patients having combination
      therapy with ChEi's. However, it is required further studies for the
      determination of clinical importance of these markers.

PMID- 20043812
TI  - The cerebrospinal fluid amyloid beta42/40 ratio in the differentiation of
      Alzheimer's disease from non-Alzheimer's dementia.
AB  - BACKGROUND: Amyloid beta(40) (Abeta(40)) is the most abundant Abeta peptide in
      the brain. The cerebrospinal fluid (CSF) level of Abeta(40) might therefore be
      considered to most closely reflect the total Abeta load in the brain. Both in
      Alzheimer's disease (AD) and in normal aging the Abeta load in the brain has a
      large inter-individual variability. Relating Abeta(42) to Abeta(40) levels might
      consequently provide a more valid measure for reflecting the change in Abeta
      metabolism in dementia patients than the CSF Abeta(42) concentrations alone. This
      measure may also improve differential diagnosis between AD and other dementia
      syndromes, such as vascular dementia (VaD), dementia with Lewy bodies (DLB), and
      frontotemporal dementia (FTD). OBJECTIVE: To investigate the diagnostic value of
      the CSF Abeta(42)/Abeta(40) ratio in differentiating AD from controls, VaD, DLB
      and FTD. METHODS: We analysed the CSF Abeta(42)/Abeta(40) ratio, phosphorylated
      tau(181) and total tau in 69 patients with AD, 26 patients with VaD, 16 patients
      with DLB, 27 patients with FTD, and 47 controls. RESULTS: Mean Abeta(40) levels
      were 2850 pg/ml in VaD and 2830 pg/ml in DLB patients, both significantly lower
      than in AD patients (3698 pg/ml; p<0.01). Abeta(40) levels in AD patients were
      not significantly different from those in controls (4035 pg/ml; p=0.384). The
      Abeta(42)/Abeta(40) ratio was significantly lower in AD patients than in all
      other groups (p <0.001, ANCOVA). Differentiating AD from VaD, DLB and non-AD
      dementia improved when the Abeta(42)/Abeta(40) ratio was used instead of
      Abeta(42) concentrations alone (p<0.01) The Abeta(42)/Abeta(40) ratio performed
      equally well as the combination of Abeta(42), phosphorylated tau(181) and total
      tau in differentiating AD from FTD and non-AD dementia. The diagnostic
      performance of the latter combination was not improved when the
      Abeta(42)/Abeta(40) ratio was used instead of Abeta(42) alone. CONCLUSION: The
      CSF Abeta42/Abeta40 ratio improves differentiation of AD patients from VaD, DLB
      and non-AD dementia patients, when compared to Abeta42 alone, and is a more
      easily interpretable alternative to the combination of Abeta42, p-tau and t-tau
      when differentiating AD from either FTD or non-AD dementia.

PMID- 20043813
TI  - Oral health in Alzheimer's disease: a review.
AB  - The main data on oral health and dental pathologies affecting Alzheimer's disease
      (AD) patients were reviewed. Oral health declines and dental pathologies increase
      with progression of AD. Poor oral hygiene, difficulty in wearing dentures, and
      the inability to self-care, including carrying out oral hygiene procedures are
      the most probable cause of impaired oral health in AD. Collection of information
      on oral/dental conditions from AD patients or their caregivers/relatives is often
      difficult and scientific literature on the topic is sparse . The majority of data
      on the subject consist in retrospective studies affected to some extent by
      subjective views of dental professionals involved. Appropriate dental
      interventions in adult-onset dementia disorders will decrease pain and oral
      pathology and consequently could contribute to maintain enough oral and
      nutritional health in these patients. Dental treatment in early stages of the
      disease are important and should be finalized at producing a stable oral
      condition. This could improve the quality of life and contribute to decrease
      worsening of oral situations in the later stages of the disease when dental
      treatment may be difficult. The problem of awareness of good oral health for
      keeping quality of life more acceptable in adult-onset dementia disorders is
      discussed.

PMID- 20043814
TI  - Up-regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-target genes in
      cortical neurons by the novel multifunctional iron chelator anti-Alzheimer drug,
      M30.
AB  - Based on a multimodal drug design paradigm, we have synthesized a multifunctional
      non-toxic, brain permeable iron chelator, M30, possessing the neuroprotective
      propargylamine moiety of the anti-Parkinsonian drug, rasagiline (Azilect) and
      antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of our iron
      chelator, VK28. M30 was recently found to confer potential neuroprotective
      effects in vitro and in various preclinical neurodegenerative models and regulate
      the levels and processing of the Alzheimer's amyloid precursor protein and its
      toxic amyloidogenic derivative, Abeta. Here, we show that M30 activates the
      hypoxia-inducible factor (HIF)-1alpha signaling pathway, thus promoting HIF
      1alpha mRNA and protein expression levels, as well as increasing transcription of
      HIF-1alpha-dependent genes, including vascular endothelial growth factor,
      erythropoietin, enolase-1, p21 and tyrosine hydroxylase in rat primary cortical
      cells. In addition, M30 also increased the expression levels of the transcripts
      of brain derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP
      43). Regarding aspects of relevance to Alzheimer's disease (AD), western blotting
      analysis of glycogen synthase kinase- 3beta (GSK-3beta) signaling pathway
      revealed that M30 enhanced the levels of phospho-AKT (Ser473) and phospho- GSK
      3beta (Ser9) and attenuated Tau phosphorylation. M30 was also shown to protect
      cultured cortical neurons against Abeta(25-35) toxicity. All these multimodal
      pharmacological activities of M30 might be beneficial for its potent efficacy in
      the prevention and treatment of neurodegenerative conditions, such as Parkinson's
      disease and AD in which oxidative stress and iron-mediated toxicity are involved.

PMID- 20043815
TI  - Waveform analysis of non-oscillatory independent components in single-trial
      auditory event-related activity in healthy subjects and Alzheimer's disease
      patients.
AB  - The objective was to characterize the non-oscillatory independent components
      (ICs) of the auditory event-related potential (ERP) waveform of an oddball task
      for normal and newly diagnosed Alzheimer's disease (AD) subjects, and to seek
      biomarkers for AD. Single trial ERP waveforms were analysed using independent
      components analysis (ICA) and k-means clustering. Two stages of clustering
      depended upon the magnitudes and latencies, and the scalp topographies of the non
      oscillatory back-projected ICs (BICs) at electrode Cz. The electrical current
      dipole sources of the BICs were located using Low Resolution Electromagnetic
      Tomography (LORETA). Generally 3-10 BICs, of different latencies and polarities,
      occurred in each trial. Each peak was associated with positive and negative BICs.
      The trial-to-trial variations in their relative numbers and magnitudes may
      explain the variations in the averaged ERP reported, and the delay in the
      averaged P300 for AD patients. The BIC latencies, topographies and electrical
      current density maximum locations varied from trial-to-trial. Voltage foci in the
      BIC topographies identify the BIC source locations. Since statistical differences
      were found between the BICs in healthy and AD subjects, the method might provide
      reliable biomarkers for AD, if these findings are reproduced in a larger study,
      independently of other factors influencing the comparison of the two populations.
      The method can extract artefact- and EEG-free single trial ERP waveforms, offers
      improved ERP averages by selecting the trials on the basis of their BICs, and is
      applicable to other evoked potentials, conditions and diseases.

PMID- 20043816
TI  - Double-blind, controlled phase II study of a 5-HT6 receptor antagonist, SB
      742457, in Alzheimer's disease.
AB  - BACKGROUND: This randomized, double-blind, placebo-controlled study investigated
      the efficacy and tolerability of the 5-HT6 receptor antagonist, SB-742457, in
      subjects with mild-to-moderate probable Alzheimer's disease (AD). METHODS:
      Participating subjects had a Mini-Mental State Examination (MMSE) score of 12 to
      26 after a 4-week, single-blind, placebo run-in phase, and were randomized
      (2:1:1:2) to receive placebo, SB-742457 5 mg, 15 mg, or 35 mg once daily for 24
      weeks. Coprimary efficacy endpoints were the Clinician's Interview-Based
      Impression of Change with caregiver input (CIBIC+) score and change from baseline
      in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) score at
      Week 24, in the intent-to-treat (ITT) population. A model-based design provided
      90% power to detect a linear trend in treatment response across increasing doses
      and > or =90% power to compare SB-742457 35 mg with placebo. RESULTS: 371
      subjects were randomized. In the ITT population (n=357), linear trend analysis at
      Week 24 suggested a dose response for CIBIC+ with a mean slope of -0.05 points/5
      mg dose increase (95% confidence interval [CI]: -0.09, -0.01; p=0.016). The dose
      response slope for change from baseline in ADAS-Cog was -0.22 points/5-mg dose
      increase (95% CI: -0.45, 0.01; p=0.059). The adjusted mean treatment difference
      from placebo at Week 24 for SB-742457 35 mg (-0.31) was significant on CIBIC+
      (95% CI: -0.62, -0.00; p=0.047) but non-significant on ADAS-Cog (-1.28 [95% CI: 
      2.96, 0.40]; p=0.135). Adverse events occurred in 24-37% in the SB-742457 groups
      vs 29% for placebo; 11-16% discontinued SB-742457 vs 15% for placebo. COMMENTS:
      SB-742457 was generally safe and well tolerated and may be efficacious in AD.

PMID- 20043817
TI  - Synchronized communication between people with dementia and their volunteer
      caregivers. A video-based explorative study on temporal aspects of interaction
      and the transfer to education.
AB  - Processes of demographic change are leading to decreasing human resources in
      professional as well as lay care; this decrease necessitates new concepts of
      care, especially for the growing number of people with dementia (p.w.d.). Since
      the amendment to the German Care Insurance Law (2002), family carers have been
      entitled to regular weekly relief, provided by volunteers who have been given a
      thirty-hour-training. As difficulties in information processing in p.w.d. form an
      important part of the symptoms in dementia sufferers--with a high impact on
      communication as well as competent functioning in activities associated with
      daily life, we wanted to establish how much awareness and sensitivity voluntary
      attendants show in "tuning in" to the p.w.d. and her/his individual capacity to
      interact. In an exploratory study the authors analyzed videotaped interactions
      between volunteer caregivers and dementia-sufferers which were recorded in
      everyday situations during the process of ongoing care. Using methods of Video
      Interaction Analysis and Grounded Theory, we developed categories which describe
      how in tune the helpers are with the timing skills--or lack of them--of p.w.d..
      We think that understanding the different ways in which p.w.d. structure their
      time can improve their communication and interaction. The categories --"speed and
      adjustment of speed", "mutuality" and "time control"--seemed crucial in
      understanding the subsequent course of the interactions. In a second step, these
      categories have recently been used by students and staff of the Lausitz
      University of Applied Sciences to provide training that sensitizes volunteer
      attendants to the topic and to learn about volunteers; judgement on the
      importance of continuing education in this field.

PMID- 20043818
TI  - Quantum dots improve peptide detection in MALDI MS in a size dependent manner.
AB  - Laser Desorption Ionization Mass Spectrometry employs matrix which is co
      crystallised with the analyte to achieve "soft ionization" that is the formation
      of ions without fragmentation. A variety of matrix-free and matrix-assisted LDI
      techniques and matrices have been reported to date. LDI has been achieved using
      ultra fine metal powders (UFMPs), desorption ionisation on silicon (DIOS), sol
      gel assisted laser desorption/ionization (SGALDI), as well as with common MALDI
      matrices such as 2,5-dihydroxy benzoic acid (DHB), 3,5-dimethoxy-4
      hydroxycinnamic acid (SA), alpha-cyano-4-hydroxycinnamic acid (CHCA) to name a
      few. A variety of matrix additives have been shown to improve matrix assisted
      desorption, including silicon nanowires (SiNW), carbon nanotubes (CNT), metal
      nanoparticles and nanodots. To our knowledge no evidence exists for the
      application of highly fluorescent CdSe/ZnS quantum dots to enhance MALDI
      desorption of biological samples. Here we report that although CdSe/ZnS quantum
      dots on their own can not substitute matrix in MALDI-MS, their presence has a
      moderately positive effect on MALDI desorption, improves the signal-to-noise
      ratio, peak quality and increases the number of detected peptides and the overall
      sequence coverage.

PMID- 20043819
TI  - Clarifying "never events and introducing "always events".

PMID- 20043820
TI  - Benefits of global partnerships to facilitate access to medicines in developing
      countries: a multi-country analysis of patients and patient outcomes in GIPAP.
AB  - BACKGROUND: Access to medicines in developing countries continues to be a
      significant problem due to lack of insurance and lack of affordability. Chronic
      Myeloid Leukemia (CML), a rare disease, can be treated effectively, but the
      pharmaceutical treatment available (imatinib) is costly and unaffordable by most
      patients. GIPAP, is a programme set up between a manufacturer and an NGO to
      provide free treatment to eligible CML patients in 80 countries worldwide.
      OBJECTIVES: To discuss the socio-economic and demographic characteristics of
      patients participating in GIPAP; to research the impact GIPAP is having on health
      outcomes (survival) of assistance-eligible CML patients; and to discuss the
      determinants of such outcomes and whether there are any variations according to
      socio-economic, demographic, or geographical criteria. METHODS: Data for 13,568
      patients across 15 countries, available quarterly, were analysed over the 2005
      2007 period. Ordered Probit panel data analysis was used to analyze the
      determinants of a patient's progress in terms of participation in the programme.
      Four waves of patients entering quarterly in 2005 were used to evaluate patient
      survival over the sample period. RESULTS: All patients in the sample are eligible
      to receive treatment provided they report to a facility quarterly. 62.3% of
      patients were male and 37.7% female. The majority (84.4%) entered during the
      chronic phase of the disease and their average age was 38.4 years. Having
      controlled for age, location and occupation, the analysis showed that patients
      were significantly much more likely to move towards a better health state after
      receiving treatment irrespective of their disease stage at the point of entry to
      the program (OR = 30.5, alpha = 1%); and that the larger the gap between
      diagnosis and approval for participation in the program, the more likely it is
      that patients' condition deteriorates (OR = 0.995, alpha = 1%), due to absence of
      treatment. Regressions to account for the effect of large countries (India,
      China, Pakistan) did not show any important differences when compared to the
      remaining countries in the sample. Survival analysis shows that at least 66
      percent of all patients that entered the program in 2005 were alive and active by
      the end of 2007. CONCLUSIONS: GIPAP has a significant positive effect on patient
      access to important medicines for a life threatening condition such as CML. It
      impacts both the progress and phase of the disease and leads to a high survival
      rate. Overall, it sets a good example for access to treatment in developing
      countries, where such programmes can substitute or complement local efforts to
      provide care to eligible patients.

PMID- 20043821
TI  - Evaluating NAT2PRED for inferring the individual acetylation status from unphased
      genotype data.
AB  - BACKGROUND: Genetically determined differences in N-acetylation capacity have
      proved to be important determinants of both the effectiveness of therapeutic
      response and the development of adverse drug reactions and toxicity during drug
      treatment. NAT2PRED is a web-server that allows a fast determination of NAT2
      acetylation phenotype from genotype data without taking the extra step of
      reconstructing haplotypes for each individual (publicly available at
      http://nat2pred.rit.albany.edu). However, the classification accuracy of NAT2PRED
      needs to be assessed before its application can be advocated at a large scale.
      METHODS: The ability of NAT2PRED to classify individuals according to their
      acetylation status (slow, intermediate and rapid acetylators) was evaluated in a
      worldwide dataset composed of 56 population samples (8,489 individuals) from four
      continental regions. RESULTS: NAT2PRED correctly identified slow acetylators with
      a sensitivity above 99% for all populations outside sub-Saharan Africa.
      Nevertheless, NAT2PRED showed a poor ability to distinguish between intermediate
      and rapid acetylators, with a classification error rate reaching up to 10% in the
      non-African samples. CONCLUSION: NAT2PRED is an excellent tool to infer the
      individual acetylation status from NAT2 genotype data when the main interest is
      to distinguish slow acetylators from the others. This should facilitate the
      determination of the individual acetylation status in routine clinical practice
      and lead to better monitoring of risks associated with cancer and adverse drug
      reactions.

PMID- 20043822
TI  - Giant cell tumor-like lesion of the urinary bladder: a report of two cases and
      literature review; giant cell tumor or undifferentiated carcinoma?
AB  - Giant cell tumor, excluding its prototype in bone, is usually a benign but local
      aggressive neoplasm originating from tendon sheath or soft tissue. Malignant
      behavior is uncommon. Visceral organ involvement including urinary bladder is
      rare. Giant cell tumors in visceral organs usually accompany epithelial tumors
      and the clinical behavior of giant cell tumor in urinary bladder is similar to
      its bone counterpart. Here, we report two cases of giant cell tumor located in
      urinary bladder in comparison with nine reported cases in the English literature.
      Concurrent noninvasive urothelial carcinoma was also described in all these
      previous reports and only one patient with follow-up died of disease. One of the
      two cases we present had no concurrent urothelial tumor at the time of diagnosis
      but had a history of a low grade noninvasive urothelial carcinoma with three
      recurrences. The histology of these two cases was similar to the giant cell tumor
      of bone and composed of oval to spindle mononuclear cells with evenly spaced
      osteoclast-like giant cells. Immunohistochemically, the giant cells showed
      staining with osteoclastic markers including CD68, TRAP, and LCA.
      Immunohistochemical expression of vimentin, CD68, LCA, and smooth muscle actin in
      mononuclear cells supported a mesenchymal origin with histiocytic lineage. The
      histologic and immunohistochemical properties in our cases as well as their
      clinical courses were consistent with a giant cell tumor. Consequently, tumors in
      urinary bladder showing features of giant cell tumor of bone may also be
      considered and termed "giant cell tumor".

PMID- 20043823
TI  - AtPIN: Arabidopsis thaliana protein interaction network.
AB  - BACKGROUND: Protein-protein interactions (PPIs) constitute one of the most
      crucial conditions to sustain life in living organisms. To study PPI in
      Arabidopsis thaliana we have developed AtPIN, a database and web interface for
      searching and building interaction networks based on publicly available protein
      protein interaction datasets. DESCRIPTION: All interactions were divided into
      experimentally demonstrated or predicted. The PPIs in the AtPIN database present
      a cellular compartment classification (C3) which divides the PPI into 4 classes
      according to its interaction evidence and subcellular localization. It has been
      shown in the literature that a pair of genuine interacting proteins are generally
      expected to have a common cellular role and proteins that have common interaction
      partners have a high chance of sharing a common function. In AtPIN, due to its
      integrative profile, the reliability index for a reported PPI can be postulated
      in terms of the proportion of interaction partners that two proteins have in
      common. For this, we implement the Functional Similarity Weight (FSW) calculation
      for all first level interactions present in AtPIN database. In order to identify
      target proteins of cytosolic glutamyl-tRNA synthetase (Cyt-gluRS) (AT5G26710) we
      combined two approaches, AtPIN search and yeast two-hybrid screening.
      Interestingly, the proteins glutamine synthetase (AT5G35630), a disease
      resistance protein (AT3G50950) and a zinc finger protein (AT5G24930), which has
      been predicted as target proteins for Cyt-gluRS by AtPIN, were also detected in
      the experimental screening. CONCLUSIONS: AtPIN is a friendly and easy-to-use tool
      that aggregates information on Arabidopsis thaliana PPIs, ontology, and sub
      cellular localization, and might be a useful and reliable strategy to map protein
      protein interactions in Arabidopsis. AtPIN can be accessed at
      http://bioinfo.esalq.usp.br/atpin.

PMID- 20043824
TI  - Evidence-based practice implementation: the impact of public versus private
      sector organization type on organizational support, provider attitudes, and
      adoption of evidence-based practice.
AB  - BACKGROUND: The goal of this study is to extend research on evidence-based
      practice (EBP) implementation by examining the impact of organizational type
      (public versus private) and organizational support for EBP on provider attitudes
      toward EBP and EBP use. Both organization theory and theory of innovation uptake
      and individual adoption of EBP guide the approach and analyses in this study. We
      anticipated that private sector organizations would provide greater levels of
      organizational support for EBPs leading to more positive provider attitudes
      towards EBPs and EBP use. We also expected attitudes toward EBPs to mediate the
      association of organizational support and EBP use. METHODS: Participants were
      mental health service providers from 17 communities in 16 states in the United
      States (n = 170). Path analyses were conducted to compare three theoretical
      models of the impact of organization type on organizational support for EBP and
      of organizational support on provider attitudes toward EBP and EBP use. RESULTS:
      Consistent with our predictions, private agencies provided greater support for
      EBP implementation, and staff working for private agencies reported more positive
      attitudes toward adopting EBPs. Organizational support for EBP partially mediated
      the association of organization type on provider attitudes toward EBP.
      Organizational support was significantly positively associated with attitudes
      toward EBP and EBP use in practice. CONCLUSION: This study offers further support
      for the importance of organizational context as an influence on organizational
      support for EBP and provider attitudes toward adopting EBP. The study
      demonstrates the role organizational support in provider use of EBP in practice.
      This study also suggests that organizational support for innovation is a
      malleable factor in supporting use of EBP. Greater attention should be paid to
      organizational influences that can facilitate the dissemination and
      implementation of EBPs in community settings.

PMID- 20043825
TI  - Estrogen and inflammation modulate estrogen receptor alpha expression in specific
      tissues of the temporomandibular joint.
AB  - BACKGROUND: Estrogen is known to play role in temporomandibular joint (TMJ)
      disorders and estrogen effects can be mediated by estrogen receptor (ER) alpha
      present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in
      the temporomandibular joint (TMJ) but changes in expression due to estrogen and
      inflammation have not been characterized. In this study, ERalpha protein content
      and the number of cells expressing ERalpha was measured in 17 beta-estradiol
      treated rats after inflammation was induced in the TMJ. METHODS: Sixteen
      ovariectomized female rats were divided into two groups such that one group
      received 17 beta estradiol (E2) and the other was given vehicle (VEH). Groups
      were then subdivided further, one received injections of saline and the other
      received Complete Freund's adjuvant (CFA) within the superior joint space of the
      TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA.
      After treatment, the rats were sacrificed, and the TMJ anterior, disc,
      retrodiscal and synovial tissues were analyzed by western blot and
      immunocytochemistry. Positive stained cells were counted using a Nikon
      epifluorescent microscope. RESULTS: The western blot showed that ERalpha protein
      significantly decreased with inflammation. The number of ERalpha-positive cells
      in the TMJ was not affected by inflammation or 17 beta-estradiol with exception
      of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol
      significantly decreased the number of ERalpha-positive cells but only in a non
      inflamed joint. CONCLUSIONS: In conclusion, inflammation and 17 beta-estradiol
      can modulate ERalpha expression in the TMJ but the effects are tissue specific.

PMID- 20043826
TI  - The chlamydial functional homolog of KsgA confers kasugamycin sensitivity to
      Chlamydia trachomatis and impacts bacterial fitness.
AB  - BACKGROUND: rRNA adenine dimethyltransferases, represented by the Escherichia
      coli KsgA protein, are highly conserved phylogenetically and are generally not
      essential for growth. They are responsible for the post-transcriptional transfer
      of two methyl groups to two universally conserved adenosines located near the
      3'end of the small subunit rRNA and participate in ribosome maturation. All
      sequenced genomes of Chlamydia reveal a ksgA homolog in each species, including
      C. trachomatis. Yet absence of a S-adenosyl-methionine synthetase in Chlamydia,
      the conserved enzyme involved in the synthesis of the methyl donor S-adenosyl-L
      methionine, raises a doubt concerning the activity of the KsgA homolog in these
      organisms. RESULTS: Lack of the dimethylated adenosines following ksgA
      inactivation confers resistance to kasugamycin (KSM) in E. coli. Expression of
      the C. trachomatis L2 KsgA ortholog restored KSM sensitivity to the E. coli ksgA
      mutant, suggesting that the chlamydial KsgA homolog has specific rRNA dimethylase
      activity. C. trachomatis growth was sensitive to KSM and we were able to isolate
      a KSM resistant mutant of C. trachomatis containing a frameshift mutation in
      ksgA, which led to the formation of a shorter protein with no activity. Growth of
      the C. trachomatis ksgA mutant was negatively affected in cell culture
      highlighting the importance of the methylase in the development of these obligate
      intracellular and as yet genetically intractable pathogens. CONCLUSION: The
      presence of a functional rRNA dimethylase enzyme belonging to the KsgA family in
      Chlamydia presents an excellent chemotherapeutic target with real potential. It
      also confirms the existence of S-adenosyl-methionine--dependent methylation
      reactions in Chlamydia raising the question of how these organisms acquire this
      cofactor.

PMID- 20043827
TI  - Deregressing estimated breeding values and weighting information for genomic
      regression analyses.
AB  - BACKGROUND: Genomic prediction of breeding values involves a so-called training
      analysis that predicts the influence of small genomic regions by regression of
      observed information on marker genotypes for a given population of individuals.
      Available observations may take the form of individual phenotypes, repeated
      observations, records on close family members such as progeny, estimated breeding
      values (EBV) or their deregressed counterparts from genetic evaluations. The
      literature indicates that researchers are inconsistent in their approach to using
      EBV or deregressed data, and as to using the appropriate methods for weighting
      some data sources to account for heterogeneous variance. METHODS: A logical
      approach to using information for genomic prediction is introduced, which
      demonstrates the appropriate weights for analyzing observations with
      heterogeneous variance and explains the need for and the manner in which EBV
      should have parent average effects removed, be deregressed and weighted. RESULTS:
      An appropriate deregression for genomic regression analyses is EBV/r2 where EBV
      excludes parent information and r2 is the reliability of that EBV. The
      appropriate weights for deregressed breeding values are neither the reliability
      nor the prediction error variance, two alternatives that have been used in
      published studies, but the ratio (1 - h2)/[(c + (1 - r2)/r2)h2] where c > 0 is
      the fraction of genetic variance not explained by markers. CONCLUSIONS:
      Phenotypic information on some individuals and deregressed data on others can be
      combined in genomic analyses using appropriate weighting.

PMID- 20043828
TI  - Microdialysis assessment of peripheral metabolism in critical limb ischemia after
      endovascular revascularization.
AB  - BACKGROUND: Critical limb ischemia is a chronic pathologic condition defined by
      the lack of blood flow in peripheral circulation. Microdialysis is a well-known
      and sensitive method for the early detection of tissue ischemia. The aim of the
      present study was to use microdialysis in order to analyse cellular metabolism
      changes after peripheral endovascular revascularization. METHODS: Ten patients
      diagnosed with critical limb ischemia was enrolled. CMA 60 (CMA-Solna, Sweden)
      catheter with a 20 kDa cut-off was placed subcutaneously on the anterior aspect
      of the foot of both limbs. Samples were collected starting 12-hours before
      surgery and throughout the following 72-hours, using a CMA 600 (CMA-Solna,
      Sweden) microdialysis analyser. RESULTS: Technical revascularization was
      successful in all cases. The cannulation was well tolerated in all patients. The
      site of catheter insertion healed easily in few days without infective
      complications in any case. Two patients underwent major amputation. After
      revascularization, glucose showed a strong increase (mean, 5.86 +/- 1.52 mMol/L,
      p = .008). No restoration of the circadian rhythm was noted in patients who
      underwent major amputation. Glycerol concentration curves were not deductibles in
      both the ischemic and the control limbs (mean, 148.43 +/- 42.13 mMol/L vs 178.44
      +/- 75.93 mMol/L, p = .348). Within the first 24-hours after revascularization,
      lactate concentration raised strongly (6.58 +/- 1.56 mMol/L, p = .002):
      thereafter, it immediately decreased to a concentration similar to the control
      level (1.71 +/- 1.69 mMol/L). In both patients who underwent major amputation,
      lactate did not show the typical peak of the successful revascularization. The
      trend of the lactate/pyruvate ratio after a brief initial decrease of the ratio
      increased again in both the patients who finally underwent amputation.
      CONCLUSIONS: Restoration of glucose and glycerol circadian rhythm, coupled with
      low lactate concentration and lactate/pyruvate ratio seemed to be linked to good
      surgical outcome.

PMID- 20043829
TI  - Treatment of psychotic symptoms in bipolar disorder with aripiprazole
      monotherapy: a meta-analysis.
AB  - BACKGROUND: We present a systematic review and meta-analysis of the available
      clinical trials concerning the usefulness of aripiprazole in the treatment of the
      psychotic symptoms in bipolar disorder. METHODS: A systematic MEDLINE and
      repository search concerning clinical trials for aripiprazole in bipolar disorder
      was conducted. RESULTS: The meta-analysis of four randomised controlled trials
      (RCTs) on acute mania suggests that the effect size of aripiprazole versus
      placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for
      the total Positive and Negative Syndrome Scale (PANSS) score. The effect was
      higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24)
      and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale
      (0.12). No data on the depressive phase of bipolar illness exist, while there are
      some data in favour of aripiprazole concerning the maintenance phase, where at
      week 26 all except the total PANSS score showed a significant superiority of
      aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and
      d = 0.71 for the hostility subscales) and at week 100 the results were similar (d
      = 0.42, 0.63 and 0.48, respectively). CONCLUSION: The data analysed for the
      current study support the usefulness of aripiprazole against psychotic symptoms
      during the acute manic and maintenance phases of bipolar illness.

PMID- 20043830
TI  - Determining and addressing obstacles to the effective use of long-lasting
      insecticide-impregnated nets in rural Tanzania.
AB  - BACKGROUND: The objective of this project was to achieve high, sustainable levels
      of net coverage in a village in rural Tanzania by combining free distribution of
      long-lasting insecticide-impregnated nets (LLINs) with community-tailored
      education. In Tanzania, malaria is the leading cause of morbidity and mortality.
      Although malaria bed nets have a well-established role in reducing disease
      burden, few rural households have access to nets, and effective use depends on
      personal practices and attitudes. METHODS: Five practices and attitudes
      inconsistent with effective LLIN use were identified from household interviews (n
      = 10). A randomized survey of villagers (n = 132) verified local prevalence of
      these practices and attitudes. Community leaders held an educational session for
      two members of every household addressing these practice and attitudes,
      demonstrating proper LLIN use, and emphasizing behaviour modification. Attendees
      received one or two LLINs per household. Surveys distributed three weeks (n =
      104) and 15 months (n = 104) post-intervention assessed corrected practices and
      attitudes. Project efficacy was defined by correction of baseline practices and
      attitudes as well as high rates of reported daily net use, with statistical
      significance determined by chi-square test. RESULTS: Baseline interviews and
      surveys revealed incorrect practices and attitudes regarding 1) use of nets in
      dry season, 2) need to retreat LLINs, 3) children napping under nets, 4) need to
      repair nets, and 5) net procurement as a priority, with 53- 88.6% incorrect
      responses (11.4-47% correct responses). A three-week follow-up demonstrated 83
      95% correct responses. Fifteen-month follow-up showed statistically significant
      (p < 0.01) corrections from baseline in all five practice and attitudes (39.4
      93.3% correct answers). 89.4% of respondents reported using their nets every
      night, and 93.3% affirmed purchase of nets as a financial priority. CONCLUSIONS:
      Results suggest that addressing community-specific practices and attitudes prior
      to LLIN distribution promotes consistent and correct use, and helps change
      attitudes towards bed nets as a preventative health measure. Future LLIN
      distributions can learn from the paradigm established in this project.

PMID- 20043831
TI  - The effectiveness of physical activity monitoring and distance counselling in an
      occupational health setting--a research protocol for a randomised controlled
      trial (CoAct).
AB  - BACKGROUND: The CoAct (Cocreating Activity) study is investigating a novel
      lifestyle intervention, aimed at the working population, with daily activity
      monitoring and distance counselling via telephone and secure web messages. The
      main purpose of this study is to evaluate the effectiveness of lifestyle
      counselling on the level of physical activity in an occupational health setting.
      The purposes include also analysing the potential effects of changes in physical
      activity on productivity at work and sickness absence, and healthcare costs. This
      article describes the design of the study and the participant flow until and
      including randomization. METHODS/DESIGN: CoAct is a randomised controlled trial
      with two arms: a control group and intervention group with daily activity
      monitoring and distance counselling. The intervention focuses on lifestyle
      modification and takes 12 months. The study population consists of volunteers
      from 1100 eligible employees of a Finnish insurance company. The primary outcomes
      of this study are change in physical activity measured in MET minutes per week,
      work productivity and sickness absence, and healthcare utilisation. Secondary
      outcomes include various physiological measures. Cost-effectiveness analysis will
      also be performed. The outcomes will be measured by questionnaires at baseline,
      after 6, 12, and 24 months, and sickness absence will be obtained from the
      employer's registers. DISCUSSION: No trials are yet available that have evaluated
      the effectiveness of daily physical activity monitoring and distance counselling
      in an occupational health setting over a 12 month period and no data on cost
      effectiveness of such intervention are available. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00994565.

PMID- 20043832
TI  - Anomalous constitutive Src kinase activity promotes B lymphoma survival and
      growth.
AB  - BACKGROUND: Previously we have shown that B cell receptor (BCR) expression and B
      cell receptor signaling pathways are important for the basal growth of B lymphoma
      cells. In particular we have shown that the activation of Syk, a non-src family
      protein tyrosine kinase and the mitogen activated protein kinases (MAPK), ERK and
      JNK that mediate BCR signals are required for the constitutive growth of B
      lymphoma cells. Since src family protein tyrosine kinases (SFKs) like Lyn are
      known to be needed for the phosphorylation of BCR co-receptors, Ig-alpha and Ig
      beta, we hypothesized that one or more SFKs will be constitutively activated in B
      lymphoma cells and may be necessary for B lymphoma growth. RESULTS: Src kinase
      activity was found to be constitutively high in many murine and human B lymphoma
      cell lines and primary lymphoma samples. The specific pharmacological inhibitors
      of SFKs, PP1 and PP2 inhibited the proliferation of a number of both murine and
      human B lymphomas in a dose-dependent manner. Importantly, dasatinib (BMS
      354825), an oral dual BCR-ABL and SFK specific inhibitor inhibited the growth of
      B lymphomas in the nanomolar range in vitro and strongly inhibited a mouse
      lymphoma growth in vivo. Among the SFKs, Lyn is predominantly phosphorylated and
      Lyn-specific small interfering RNA inhibited the growth of B lymphomas,
      supporting an important role for Lyn in B lymphoma growth. Suppression of SFK
      activity blocks BCR mediated signaling pathways. PMA or CpG can partially reverse
      the growth inhibition induced by SFK inhibition. Although blocking SFK activity
      inhibited the growth of a number of B lymphomas, some lymphomas such as SudHL-4,
      SudHL-6, OCI-Ly3 and OCI-Ly10 are more resistant due to an increased expression
      of the anti-apoptotic proteins Bcl-2 and Bcl-xL. CONCLUSIONS: These studies
      further support our concept that BCR signaling pathways are important for the
      continued growth of established B lymphoma cells. Some of the intermediates in
      this BCR pathway are potential immunotherapeutic targets. In particular,
      inhibition of SFK activity alone or in synergy with inhibition of the prosurvival
      Bcl-2 proteins holds promise in developing more effective treatments for B
      lymphoma patients.

PMID- 20043833
TI  - Magnetic resonance flow velocity and temperature mapping of a shape memory
      polymer foam device.
AB  - BACKGROUND: Interventional medical devices based on thermally responsive shape
      memory polymer (SMP) are under development to treat stroke victims. The goals of
      these catheter-delivered devices include re-establishing blood flow in occluded
      arteries and preventing aneurysm rupture. Because these devices alter the
      hemodynamics and dissipate thermal energy during the therapeutic procedure, a
      first step in the device development process is to investigate fluid velocity and
      temperature changes following device deployment. METHODS: A laser-heated SMP foam
      device was deployed in a simplified in vitro vascular model. Magnetic resonance
      imaging (MRI) techniques were used to assess the fluid dynamics and thermal
      changes associated with device deployment. RESULTS: Spatial maps of the steady
      state fluid velocity and temperature change inside and outside the laser-heated
      SMP foam device were acquired. CONCLUSIONS: Though non-physiological conditions
      were used in this initial study, the utility of MRI in the development of a
      thermally-activated SMP foam device has been demonstrated.

PMID- 20043834
TI  - Proteomic analysis of honeybee worker (Apis mellifera) hypopharyngeal gland
      development.
AB  - BACKGROUND: Hypopharyngeal glands (HG) of honeybee workers play an important role
      in honeybee nutrition and caste differentiation. Previous research mainly focused
      on age-dependent morphological, physiological, biochemical and genomic characters
      of the HG. Here proteomics and biochemical network analysis were used to follow
      protein changes during the HG development. RESULTS: A total of 87, 76, 85, 74,
      71, and 55 proteins were unambiguously identified on day 1, 3, 6, 12, 15 and 20,
      respectively. These proteins were major royal jelly proteins (MRJPs), metabolism
      of carbohydrates, lipids and proteins, cytoskeleton, development regulation,
      antioxidant, molecule transporter, regulation of transcription/translation,
      proteins with folding functions. The most interesting is that MRJP's that have
      been detected in the HG of the newly emerged worker bees. The MRJP's expression
      is at peak level from 6-12 days, was validated by western blot analysis of MRJP1,
      2 and 3. Moreover, 35 key node proteins were found in the biochemical networks of
      the HG. CONCLUSIONS: HG secretes RJ at peak level within 6-12 days, but the
      worker bee can secrete royal jelly (RJ) since birth, which is a new finding.
      Several key node proteins play an important role in the biochemical networks of
      the developing HG. This provides us some target proteins when genetically
      manipulating honeybees.

PMID- 20043835
TI  - A comparison of five methods to predict genomic breeding values of dairy bulls
      from genome-wide SNP markers.
AB  - BACKGROUND: Genomic selection (GS) uses molecular breeding values (MBV) derived
      from dense markers across the entire genome for selection of young animals. The
      accuracy of MBV prediction is important for a successful application of GS.
      Recently, several methods have been proposed to estimate MBV. Initial simulation
      studies have shown that these methods can accurately predict MBV. In this study
      we compared the accuracies and possible bias of five different regression methods
      in an empirical application in dairy cattle. METHODS: Genotypes of 7,372 SNP and
      highly accurate EBV of 1,945 dairy bulls were used to predict MBV for protein
      percentage (PPT) and a profit index (Australian Selection Index, ASI). Marker
      effects were estimated by least squares regression (FR-LS), Bayesian regression
      (Bayes-R), random regression best linear unbiased prediction (RR-BLUP), partial
      least squares regression (PLSR) and nonparametric support vector regression (SVR)
      in a training set of 1,239 bulls. Accuracy and bias of MBV prediction were
      calculated from cross-validation of the training set and tested against a test
      team of 706 young bulls. RESULTS: For both traits, FR-LS using a subset of SNP
      was significantly less accurate than all other methods which used all SNP.
      Accuracies obtained by Bayes-R, RR-BLUP, PLSR and SVR were very similar for ASI
      (0.39-0.45) and for PPT (0.55-0.61). Overall, SVR gave the highest accuracy.All
      methods resulted in biased MBV predictions for ASI, for PPT only RR-BLUP and SVR
      predictions were unbiased. A significant decrease in accuracy of prediction of
      ASI was seen in young test cohorts of bulls compared to the accuracy derived from
      cross-validation of the training set. This reduction was not apparent for PPT.
      Combining MBV predictions with pedigree based predictions gave 1.05 - 1.34 times
      higher accuracies compared to predictions based on pedigree alone. Some methods
      have largely different computational requirements, with PLSR and RR-BLUP
      requiring the least computing time. CONCLUSIONS: The four methods which use
      information from all SNP namely RR-BLUP, Bayes-R, PLSR and SVR generate similar
      accuracies of MBV prediction for genomic selection, and their use in the
      selection of immediate future generations in dairy cattle will be comparable. The
      use of FR-LS in genomic selection is not recommended.

PMID- 20043836
TI  - Relationship between carotid intima-media thickness and coronary angiographic
      findings: a prospective study.
AB  - BACKGROUND: Since cardiovascular diseases are associated with high mortality and
      generally undiagnosed before the onset of clinical findings, there is a need for
      a reliable tool for early diagnosis. Carotid intima-media thickness (CIMT) is a
      non-invasive marker of coronary artery disease (CAD) and is widely used in
      practice as an inexpensive, reliable, and reproducible method. In the current
      study, we aimed to investigate prospectively the relationship of CIMT with the
      presence and extent of significant coronary artery narrowing in patients
      evaluated by coronary angiography for stable angina pectoris. METHODS: One
      hundred consecutive patients with stable angina pectoris and documented ischemia
      on a stress test were included in the study. The patients were divided into two
      groups according to the result of the coronary angiography: group 1 (39 patients)
      without a noncritical coronary lesion, and group 2 (61 patients) having at least
      one lesion more than 50% within the main branches of the coronary arteries. All
      of the patients underwent carotid Doppler ultrasound examination for measurement
      of the CIMT by a radiologist blinded to the angiographic data. RESULTS: The mean
      CIMT was 0.78 +/- 0.21 mm in Group 1, while it was 1.48 +/- 0.28 mm in Group 2 (p
      = 0.001). The mean CIMT in patients with single vessel disease, multi-vessel
      disease, and left main coronary artery disease were significantly higher compared
      to Group 1 (1.2 +/- 0.34 mm, p = 0.02; 1.6 +/- 0.32 mm, p = 0.001; and 1.8 +/-
      0.31 mm, p = 0.0001, respectively). Logistic regression analysis identified CIMT
      (OR 4.3, p < 0.001) and hypertension (OR 2.4, p = 0.04) as the most important
      factors for predicting CAD. CONCLUSIONS: The findings of this study show that
      increase in CIMT is associated with the presence and extent of CAD. In
      conclusion, we demonstrated the usefulness of carotid intima-media thickness in
      predicting coronary artery disease but large-scale studies are required to define
      its role in clinical practice.

PMID- 20043837
TI  - A semiparametric cluster detection method--a comprehensive power comparison with
      Kulldorff's method.
AB  - BACKGROUND: A semiparametric density ratio method which borrows strength from two
      or more samples can be applied to moving window of variable size in cluster
      detection. The method requires neither the prior knowledge of the underlying
      distribution nor the number of cases before scanning. In this paper, the
      semiparametric cluster detection procedure is combined with Storey's q-value, a
      type of controlling false discovery rate (FDR) method, to take into account the
      multiple testing problem induced by the overlapping scanning windows. RESULTS: It
      is shown by simulations that for binary data, using Kulldorff's Northeastern
      benchmark data, the semiparametric method and Kulldorff's method performs
      similarly well. When the data are not binary, the semiparametric methodology
      still works in many cases, but Kulldorff's method requires the choices of a
      correct probability model, namely the correct scan statistic, in order to achieve
      comparable power as the semiparametric method achieves. Kulldorff's method with
      an inappropriate probability model may lose power. CONCLUSIONS: The
      semiparametric method proposed in the paper can achieve good power when detecting
      localized cluster. The method does not require a specific distributional
      assumption other than the tilt function. In addition, it is possible to adapt
      other scan schemes (e.g., elliptic spatial scan, flexible shape scan) to search
      for clusters as well.

PMID- 20043838
TI  - Organizational factors and depression management in community-based primary care
      settings.
AB  - BACKGROUND: Evidence-based quality improvement models for depression have not
      been fully implemented in routine primary care settings. To date, few studies
      have examined the organizational factors associated with depression management in
      real-world primary care practice. To successfully implement quality improvement
      models for depression, there must be a better understanding of the relevant
      organizational structure and processes of the primary care setting. The objective
      of this study is to describe these organizational features of routine primary
      care practice, and the organization of depression care, using survey questions
      derived from an evidence-based framework. METHODS: We used this framework to
      implement a survey of 27 practices comprised of 49 unique offices within a large
      primary care practice network in western Pennsylvania. Survey questions addressed
      practice structure (e.g., human resources, leadership, information technology
      (IT) infrastructure, and external incentives) and process features (e.g., staff
      performance, degree of integrated depression care, and IT performance). RESULTS:
      The results of our survey demonstrated substantial variation across the practice
      network of organizational factors pertinent to implementation of evidence-based
      depression management. Notably, quality improvement capability and IT
      infrastructure were widespread, but specific application to depression care
      differed between practices, as did coordination and communication tasks
      surrounding depression treatment. CONCLUSIONS: The primary care practices in the
      network that we surveyed are at differing stages in their organization and
      implementation of evidence-based depression management. Practical surveys such as
      this may serve to better direct implementation of these quality improvement
      strategies for depression by improving understanding of the organizational
      barriers and facilitators that exist within both practices and practice networks.
      In addition, survey information can inform efforts of individual primary care
      practices in customizing intervention strategies to improve depression
      management.

PMID- 20043839
TI  - Toxicity risk of non-target organs at risk receiving low-dose radiation: case
      report.
AB  - The spine is the most common site for bone metastases. Radiation therapy is a
      common treatment for palliation of pain and for prevention or treatment of spinal
      cord compression. Helical tomotherapy (HT), a new image-guided intensity
      modulated radiotherapy (IMRT), delivers highly conformal dose distributions and
      provides an impressive ability to spare adjacent organs at risk, thus increasing
      the local control of spinal column metastases and decreasing the potential risk
      of critical organs under treatment. However, there are a lot of non-target organs
      at risk (OARs) occupied by low dose with underestimate in this modern rotational
      IMRT treatment. Herein, we report a case of a pathologic compression fracture of
      the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient
      underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom
      relief. Two weeks after the radiotherapy had been completed, the first course of
      chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was
      administered. After two weeks of chemotherapy, however, the patient developed
      progressive dyspnea. A computed tomography scan of the chest revealed an
      interstitial pattern with traction bronchiectasis, diffuse ground-glass
      opacities, and cystic change with fibrosis. Acute radiation pneumonitis was
      diagnosed. Oncologists should be alert to the potential risk of radiation
      toxicities caused by low dose off-targets and abscopal effects even with highly
      conformal radiotherapy.

PMID- 20043840
TI  - In vitro modeling of host-parasite interactions: the 'subgingival' biofilm
      challenge of primary human epithelial cells.
AB  - BACKGROUND: Microbial biofilms are known to cause an increasing number of chronic
      inflammatory and infectious conditions. A classical example is chronic
      periodontal disease, a condition initiated by the subgingival dental plaque
      biofilm on gingival epithelial tissues. We describe here a new model that permits
      the examination of interactions between the bacterial biofilm and host cells in
      general. We use primary human gingival epithelial cells (HGEC) and an in vitro
      grown biofilm, comprising nine frequently studied and representative subgingival
      plaque bacteria. RESULTS: We describe the growth of a mature 'subgingival' in
      vitro biofilm, its composition during development, its ability to adapt to
      aerobic conditions and how we expose in vitro a HGEC monolayer to this biofilm.
      Challenging the host derived HGEC with the biofilm invoked apoptosis in the
      epithelial cells, triggered release of pro-inflammatory cytokines and in parallel
      induced rapid degradation of the cytokines by biofilm-generated enzymes.
      CONCLUSION: We developed an experimental in vitro model to study processes taking
      place in the gingival crevice during the initiation of inflammation. The new
      model takes into account that the microbial challenge derives from a biofilm
      community and not from planktonically cultured bacterial strains. It will
      facilitate easily the introduction of additional host cells such as neutrophils
      for future biofilm:host cell challenge studies. Our methodology may generate
      particular interest, as it should be widely applicable to other biofilm-related
      chronic inflammatory diseases.

PMID- 20043841
TI  - Identification of four novel phosphorylation sites in estrogen receptor alpha:
      impact on receptor-dependent gene expression and phosphorylation by protein
      kinase CK2.
AB  - BACKGROUND: Estrogen receptor alpha (ERalpha) phosphorylation is important for
      estrogen-dependent transcription of ER-dependent genes, ligand-independent
      receptor activation and endocrine therapy response in breast cancer. However
      ERalpha phosphorylation at the previously identified sites does not fully account
      for these receptor functions. To determine if additional ERalpha phosphorylation
      sites exist, COS-1 cells expressing human ERalpha were labeled with [32P]H3PO4 in
      vivo and ERalpha tryptic phosphopeptides were isolated to identify
      phosphorylation sites. RESULTS: Previously uncharacterized phosphorylation sites
      at serines 46/47, 282, 294, and 559 were identified by manual Edman degradation
      and phosphoamino acid analysis and confirmed by mutagenesis and phospho-specific
      antibodies. Antibodies detected phosphorylation of endogenous ERalpha in MCF-7,
      MCF-7-LCC2, and Ishikawa cancer cell lines by immunoblot. Mutation of Ser-282 and
      Ser-559 to alanine (S282A, S559A) resulted in ligand independent activation of
      ERalpha as determined by both ERE-driven reporter gene assays and endogenous pS2
      gene expression in transiently transfected HeLa cells. Mutation of Ser-46/47 or
      Ser-294 to alanine markedly reduced estradiol dependent reporter activation.
      Additionally protein kinase CK2 was identified as a kinase that phosphorylated
      ERalpha at S282 and S559 using motif analysis, in vitro kinase assays, and
      incubation of cells with CK2 kinase inhibitor. CONCLUSION: These novel ERalpha
      phosphorylation sites represent new means for modulation of ERalpha activity.
      S559 represents the first phosphorylation site identified in the extreme C
      terminus (F domain) of a steroid receptor.

PMID- 20043842
TI  - Cost-effectiveness analysis of PCR for the rapid diagnosis of pulmonary
      tuberculosis.
AB  - BACKGROUND: Tuberculosis is one of the most prominent health problems in the
      world, causing 1.75 million deaths each year. Rapid clinical diagnosis is
      important in patients who have co-morbidities such as Human Immunodeficiency
      Virus (HIV) infection. Direct microscopy has low sensitivity and culture takes 3
      to 6 weeks 123. Therefore, new tools for TB diagnosis are necessary, especially
      in health settings with a high prevalence of HIV/TB co-infection. METHODS: In a
      public reference TB/HIV hospital in Brazil, we compared the cost-effectiveness of
      diagnostic strategies for diagnosis of pulmonary TB: Acid fast bacilli smear
      microscopy by Ziehl-Neelsen staining (AFB smear) plus culture and AFB smear plus
      colorimetric test (PCR dot-blot).From May 2003 to May 2004, sputum was collected
      consecutively from PTB suspects attending the Parthenon Reference Hospital.
      Sputum samples were examined by AFB smear, culture, and PCR dot-blot. The gold
      standard was a positive culture combined with the definition of clinical PTB.
      Cost analysis included health services and patient costs. RESULTS: The AFB smear
      plus PCR dot-blot require the lowest laboratory investment for equipment (US$
      20,000). The total screening costs are 3.8 times for AFB smear plus culture
      versus for AFB smear plus PCR dot blot costs (US$ 5,635,760 versus US$ 1,498,
      660). Costs per correctly diagnosed case were US$ 50,773 and US$ 13,749 for AFB
      smear plus culture and AFB smear plus PCR dot-blot, respectively. AFB smear plus
      PCR dot-blot was more cost-effective than AFB smear plus culture, when the cost
      of treating all correctly diagnosed cases was considered. The cost of returning
      patients, which are not treated due to a negative result, to the health service,
      was higher in AFB smear plus culture than for AFB smear plus PCR dot-blot, US$
      374,778,045 and US$ 110,849,055, respectively. CONCLUSION: AFB smear associated
      with PCR dot-blot associated has the potential to be a cost-effective tool in the
      fight against PTB for patients attended in the TB/HIV reference hospital.

PMID- 20043843
TI  - Organization-wide adoption of computerized provider order entry systems: a study
      based on diffusion of innovations theory.
AB  - BACKGROUND: Computerized provider order entry (CPOE) systems have been introduced
      to reduce medication errors, increase safety, improve work-flow efficiency, and
      increase medical service quality at the moment of prescription. Making the impact
      of CPOE systems more observable may facilitate their adoption by users. We set
      out to examine factors associated with the adoption of a CPOE system for inter
      organizational and intra-organizational care. METHODS: The diffusion of
      innovation theory was used to understand physicians' and nurses' attitudes and
      thoughts about implementation and use of the CPOE system. Two online survey
      questionnaires were distributed to all physicians and nurses using a CPOE system
      in county-wide healthcare organizations. The number of complete questionnaires
      analyzed was 134 from 200 nurses (67.0%) and 176 from 741 physicians (23.8%).
      Data were analyzed using descriptive-analytical statistical methods. RESULTS:
      More nurses (56.7%) than physicians (31.3%) stated that the CPOE system
      introduction had worked well in their clinical setting (P < 0.001). Similarly,
      more physicians (73.9%) than nurses (50.7%) reported that they found the system
      not adapted to their specific professional practice (P = < 0.001). Also more
      physicians (25.0%) than nurses (13.4%) stated that they did want to return to the
      previous system (P = 0.041). We found that in particular the received relative
      advantages of the CPOE system were estimated to be significantly (P < 0.001)
      higher among nurses (39.6%) than physicians (16.5%). However, physicians'
      agreements with the compatibility of the CPOE and with its complexity were
      significantly higher than the nurses (P < 0.001). CONCLUSIONS: Qualifications for
      CPOE adoption as defined by three attributes of diffusion of innovation theory
      were not satisfied in the study setting. CPOE systems are introduced as a
      response to the present limitations in paper-based systems. In consequence, user
      expectations are often high on their relative advantages as well as on a low
      level of complexity. Building CPOE systems therefore requires designs that can
      provide rather important additional advantages, e.g. by preventing prescription
      errors and ultimately improving patient safety and safety of clinical work. The
      decision-making process leading to the implementation and use of CPOE systems in
      healthcare therefore has to be improved. As any change in health service settings
      usually faces resistance, we emphasize that CPOE system designers and healthcare
      decision-makers should continually collect users' feedback about the systems,
      while not forgetting that it also is necessary to inform the users about the
      potential benefits involved.

PMID- 20043844
TI  - Particle length-dependent titanium dioxide nanomaterials toxicity and
      bioactivity.
AB  - BACKGROUND: Titanium dioxide (TiO(2)) nanomaterials have considerable beneficial
      uses as photocatalysts and solar cells. It has been established for many years
      that pigment-grade TiO(2 )(200 nm sphere) is relatively inert when internalized
      into a biological model system (in vivo or in vitro). For this reason, TiO(2
      )nanomaterials are considered an attractive alternative in applications where
      biological exposures will occur. Unfortunately, metal oxides on the nanoscale
      (one dimension < 100 nm) may or may not exhibit the same toxic potential as the
      original material. A further complicating issue is the effect of modifying or
      engineering of the nanomaterial to be structurally and geometrically different
      from the original material. RESULTS: TiO(2 )nanospheres, short (< 5 mum) and long
      (> 15 mum) nanobelts were synthesized, characterized and tested for biological
      activity using primary murine alveolar macrophages and in vivo in mice. This
      study demonstrates that alteration of anatase TiO(2 )nanomaterial into a fibre
      structure of greater than 15 mum creates a highly toxic particle and initiates an
      inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials
      induced inflammasome activation and release of inflammatory cytokines through a
      cathepsin B-mediated mechanism. Consequently, long TiO(2 )nanobelts interact with
      lung macrophages in a manner very similar to asbestos or silica. CONCLUSIONS:
      These observations suggest that any modification of a nanomaterial, resulting in
      a wire, fibre, belt or tube, be tested for pathogenic potential. As this study
      demonstrates, toxicity and pathogenic potential change dramatically as the shape
      of the material is altered into one that a phagocytic cell has difficulty
      processing, resulting in lysosomal disruption.

PMID- 20043845
TI  - Understanding communication networks in the emergency department.
AB  - BACKGROUND: Emergency departments (EDs) are high pressure health care settings
      involving complex interactions between staff members in providing and organising
      patient care. Without good communication and cooperation amongst members of the
      ED team, quality of care is at risk. This study examined the problem-solving,
      medication advice-seeking and socialising networks of staff working in an
      Australian hospital ED. METHODS: A social network survey (Response Rate = 94%)
      was administered to all ED staff (n = 109) including doctors, nurses, allied
      health professionals, administrative staff and ward assistants. Analysis of the
      network characteristics was carried out by applying measures of density (the
      extent participants are concentrated), connectedness (how related they are),
      isolates (how segregated), degree centrality (who has most connections measured
      in two ways, in-degree, the number of ties directed to an individual and out
      degree, the number of ties directed from an individual), betweenness centrality
      (who is important or powerful), degree of separation (how many ties lie between
      people) and reciprocity (how bi-directional are interactions). RESULTS: In all
      three networks, individuals were more closely connected to colleagues from within
      their respective professional groups. The problem-solving network was the most
      densely connected network, followed by the medication advice network, and the
      loosely connected socialising network. ED staff relied on each other for help to
      solve work-related problems, but some senior doctors, some junior doctors and a
      senior nurse were important sources of medication advice for their ED colleagues.
      CONCLUSIONS: Network analyses provide useful ways to assess social structures in
      clinical settings by allowing us to understand how ED staff relate within their
      social and professional structures. This can provide insights of potential
      benefit to ED staff, their leaders, policymakers and researchers.

PMID- 20043846
TI  - Exhaled nitric oxide and airway hyperresponsiveness in workers: a preliminary
      study in lifeguards.
AB  - BACKGROUND: Airway inflammation and airway hyperresponsiveness (AHR) are two
      characteristic features of asthma. Fractional exhaled nitric oxide (FENO) has
      shown good correlation with AHR in asthmatics. Less information is available
      about FENO as a marker of inflammation from work exposures. We thus examined the
      relation between FENO and AHR in lifeguards undergoing exposure to chloramines in
      indoor pools. METHODS: 39 lifeguards at six indoor pools were given a respiratory
      health questionnaire, FENO measurements, spirometry, and a methacholine bronchial
      challenge (MBC) test. Subjects were labeled MBC+ if the forced expiratory volume
      (FEV1) fell by 20% or more. The normalized linear dose-response slope (NDRS) was
      calculated as the percentage fall in FEV1 at the last dose divided by the total
      dose given. The relation between MBC and FENO was assessed using logistic
      regression adjusting on confounding factors. The association between NDRS and log
      transformed values of FENO was tested in a multiple linear regression model.
      RESULTS: The prevalence of lifeguards MBC+ was 37.5%. In reactors, the median
      FENO was 18.9 ppb (90% of the predicted value) vs. 12.5 ppb (73% predicted) in
      non-reactors. FENO values >or= 60% of predicted values were 80% sensitive and 42%
      specific to identify subjects MBC+. In the logistic regression model no other
      factor had an effect on MBC after adjusting for FENO. In the linear regression
      model, NDRS was significantly predicted by log FENO. CONCLUSIONS: In lifeguards
      working in indoor swimming pools, elevated FENO levels are associated with
      increased airway responsiveness.

PMID- 20043847
TI  - Clinical presentation, demographics and outcome of tuberculosis (TB) in a low
      incidence area: a 4-year study in Geneva, Switzerland.
AB  - BACKGROUND: The incidence of tuberculosis (TB) in developed countries has
      decreased since the 1990s, reflecting worldwide efforts to identify and treat TB
      according to WHO recommendations. However TB remains an important public health
      problem in industrialized countries with a high proportion of cases occurring
      among subjects originating from high prevalence countries. The aim of this study
      was to describe clinical and social characteristics of patients with TB and their
      outcome in a low incidence area with a high immigration rate. METHODS: Four-year
      retrospective study based on a computerized database and subsequent review of
      medical records of all patients with TB followed at the outpatient section of the
      Division of Pulmonary Diseases, Geneva University Hospital, Switzerland. RESULTS:
      252 patients (84% foreigners, 25% asylum seekers) aged 38 +/- 19 yrs were studied
      (11% co-infected with HIV). TB was intrapulmonary (TBP) in 158 cases (63%),
      extrapulmonary (TBE) in 137 (54%), and both in 43 cases (17%). TBP was smear
      (S)+/culture (C)+ in 59%, S-/C+ in 37%, S-/C- in 4%. Smoking was significantly
      associated with cavitary disease.Time from onset of symptoms to diagnosis was 2.1
      +/- 3.1 months. Initially, 10% were asymptomatic; 35% had no general symptoms.
      Despite systematic sputum analysis (induced or spontaneous), TBP was confirmed
      only by bronchoscopy in 38 subjects (24% of TBP). Side effects requiring changes
      in treatment occurred in 38 cases (11%).Treatment was completed in 210 (83%)
      patients. In 42 cases, follow up was unsuccessful; causes were: failure (n = 2;
      0.8%), defaulters (n = 8; 3%), transfer out (n = 28; 11%) and death (n = 4;
      1.6%). Relapse rate was 0.24 per 100 patient-years. Considering S+ TBP only,
      success rate was 87%. CONCLUSION: TB in our area is predominantly a disease of
      young foreign-born subjects. Smoking appears as a possible risk factor for
      cavitary TBP. Time to diagnosis remains long. Compliance to treatment is
      satisfactory. Success rate for S+ TBP is within WHO objectives.

PMID- 20043848
TI  - Integrative approaches to the prediction of protein functions based on the
      feature selection.
AB  - BACKGROUND: Protein function prediction has been one of the most important issues
      in functional genomics. With the current availability of various genomic data
      sets, many researchers have attempted to develop integration models that combine
      all available genomic data for protein function prediction. These efforts have
      resulted in the improvement of prediction quality and the extension of prediction
      coverage. However, it has also been observed that integrating more data sources
      does not always increase the prediction quality. Therefore, selecting data
      sources that highly contribute to the protein function prediction has become an
      important issue. RESULTS: We present systematic feature selection methods that
      assess the contribution of genome-wide data sets to predict protein functions and
      then investigate the relationship between genomic data sources and protein
      functions. In this study, we use ten different genomic data sources in Mus
      musculus, including: protein-domains, protein-protein interactions, gene
      expressions, phenotype ontology, phylogenetic profiles and disease data sources
      to predict protein functions that are labelled with Gene Ontology (GO) terms. We
      then apply two approaches to feature selection: exhaustive search feature
      selection using a kernel based logistic regression (KLR), and a kernel based L1
      norm regularized logistic regression (KL1LR). In the first approach, we
      exhaustively measure the contribution of each data set for each function based on
      its prediction quality. In the second approach, we use the estimated coefficients
      of features as measures of contribution of data sources. Our results show that
      the proposed methods improve the prediction quality compared to the full
      integration of all data sources and other filter-based feature selection methods.
      We also show that contributing data sources can differ depending on the protein
      function. Furthermore, we observe that highly contributing data sets can be
      similar among a group of protein functions that have the same parent in the GO
      hierarchy. CONCLUSIONS: In contrast to previous integration methods, our
      approaches not only increase the prediction quality but also gather information
      about highly contributing data sources for each protein function. This
      information can help researchers collect relevant data sources for annotating
      protein functions.

PMID- 20043849
TI  - Effect of temperature and water activity on the production of fumonisins by
      Aspergillus niger and different Fusarium species.
AB  - BACKGROUND: Fumonisins are economically important mycotoxins which until recently
      were considered to originate from only a few Fusarium species. However recently a
      putative fumonisin gene cluster was discovered in two different Aspergillus niger
      strains followed by detection of an actual fumonisin B2 (FB2) production in four
      strains of this biotechnologically important workhorse. RESULTS: In the present
      study, a screening of 5 A. niger strains and 25 assumed fumonisin producing
      Fusarium strains from 6 species, showed that all 5 A. niger strains produced FB2
      and 23 of 25 Fusarium produced fumonisin B1 and other isoforms (fumonisin B2 and
      B3). Five A. niger and five Fusarium spp. were incubated at six different
      temperatures from 15-42 degrees C on Czapek Yeast Agar +5% salt or Potato
      Dextrose Agar. A. niger had the highest production of FB2 at 25-30 degrees C
      whereas Fusarium spp. had the maximal production of FB1 and FB2 at 20-25 degrees
      C. Addition of 2.5-5% NaCl, or 10-20% sucrose increased the FB2 production of A.
      niger, whereas addition of glycerol reduced FB2 production. All three water
      activity lowering solutes reduced the fumonisin production of the Fusarium
      species. CONCLUSION: The present study shows that the regulation of fumonisin
      production is very different in A. niger and Fusarium, and that food and feeds
      preserved by addition of sugar or salts may be good substrates for fumonisin B2
      production by A. niger.

PMID- 20043850
TI  - Differentially expressed alternatively spliced genes in malignant pleural
      mesothelioma identified using massively parallel transcriptome sequencing.
AB  - BACKGROUND: Analyses of Expressed Sequence Tags (ESTs) databases suggest that
      most human genes have multiple alternative splice variants. The alternative
      splicing of pre-mRNA is tightly regulated during development and in different
      tissue types. Changes in splicing patterns have been described in disease states.
      Recently, we used whole-transcriptome shotgun pryrosequencing to characterize 4
      malignant pleural mesothelioma (MPM) tumors, 1 lung adenocarcinoma and 1 normal
      lung. We hypothesized that alternative splicing profiles might be detected in the
      sequencing data for the expressed genes in these samples. METHODS: We developed a
      software pipeline to map the transcriptome read sequences of the 4 MPM samples
      and 1 normal lung sample onto known exon junction sequences in the comprehensive
      AceView database of expressed sequences and to count how many reads map to each
      junction. 13,274,187 transcriptome reads generated by the Roche/454 sequencing
      platform for 5 samples were compared with 151,486 exon junctions from the AceView
      database. The exon junction expression index (EJEI) was calculated for each exon
      junction in each sample to measure the differential expression of alternative
      splicing events. Top ten exon junctions with the largest EJEI difference between
      the 4 mesothelioma and the normal lung sample were then examined for differential
      expression using Quantitative Real Time PCR (qRT-PCR) in the 5 sequenced samples.
      Two of the differentially expressed exon junctions (ACTG2.aAug05 and CDK4.aAug05)
      were further examined with qRT-PCR in additional 18 MPM and 18 normal lung
      specimens. RESULTS: We found 70,953 exon junctions covered by at least one
      sequence read in at least one of the 5 samples. All 10 identified most
      differentially expressed exon junctions were validated as present by RT-PCR, and
      8 were differentially expressed exactly as predicted by the sequence analysis.
      The differential expression of the AceView exon junctions for the ACTG2 and CDK4
      genes were also observed to be statistically significant in an additional 18 MPM
      and 18 normal lung samples examined using qRT-PCR. The differential expression of
      these two junctions was shown to successfully classify these mesothelioma and
      normal lung specimens with high sensitivity (89% and 78%, respectively).
      CONCLUSION: Whole-transcriptome shotgun sequencing, combined with a downstream
      bioinformatics pipeline, provides powerful tools for the identification of
      differentially expressed exon junctions resulting from alternative splice
      variants. The alternatively spliced genes discovered in the study could serve as
      useful diagnostic markers as well as potential therapeutic targets for MPM.

PMID- 20043851
TI  - Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors.
AB  - BACKGROUND: The Fanconi anemia (FA) pathway is a multigene DNA damage response
      network implicated in the repair of DNA lesions that arise during replication or
      after exogenous DNA damage. The FA pathway displays synthetic lethal relationship
      with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are
      frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation
      (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in
      ATM through synthetic lethal interaction. Curcumin was previously identified as a
      weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of
      curcumin with better activity and specificity. RESULTS: Using a replication-free
      assay in Xenopus extracts, we screened monoketone analogs of curcumin for
      inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor.
      Mechanistic studies suggest that EF24 targets the FA pathway through inhibition
      of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24
      inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent
      manner. Survival assays revealed that EF24 specifically sensitizes FA-competent
      cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast
      with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than
      matched wild-type cells, consistent with a synthetic lethal effect between FA
      pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a
      compound structurally related to EF24 that displays similar activity in egg
      extracts and in cells. CONCLUSIONS: These results suggest that monoketone analogs
      of curcumin are potent inhibitors of the FA pathway and constitute a promising
      new class of targeted anticancer compounds.

PMID- 20043852
TI  - Significant weight loss in breastfed term infants readmitted for
      hyperbilirubinemia.
AB  - BACKGROUND: Weight loss of greater than 7% from birth weight indicates possible
      feeding problems. Inadequate oral intake causes weight loss and increases the
      bilirubin enterohepatic circulation. The objective of this study was to describe
      the association between total serum bilirubin (TSB) levels and weight loss in
      healthy term infants readmitted for hyperbilirubinemia after birth
      hospitalization. METHODS: We reviewed medical records of breastfed term infants
      who received phototherapy according to TSB levels readmitted to Caja Petrolera de
      Salud Clinic in La Paz, Bolivia during January 2005 through October 2008.
      RESULTS: Seventy-nine infants were studied (64.6% were males). The
      hyperbilirubinemia readmission rate was 5% among breastfed infants. Term infants
      were readmitted at a median age of 4 days. Mean TSB level was 18.6 +/- 3 mg/dL.
      Thirty (38%) had significant weight loss. A weak correlation between TSB levels
      and percent of weight loss was identified (r = 0.20; p < 0.05). The frequency of
      severe hyperbilirubinemia (> 20 mg/dL) was notably higher among infants with
      significant weight loss (46.7% vs. 18.4%; p < 0.05). The risk of having severe
      hyperbilirubinemia was approximately 4 times greater for infants with significant
      weight loss (OR: 3.9; 95% CI: 1.4-10.8; p < 0.05). CONCLUSIONS: Significant
      weight loss could be a useful parameter to identify breastfed term infants at
      risk of severe hyperbilirubinemia either during birth hospitalization or
      outpatient follow-up visits in settings where routine pre-discharge TSB levels
      have not been implemented yet.

PMID- 20043853
TI  - Prioritizing genes for follow-up from genome wide association studies using
      information on gene expression in tissues relevant for type 2 diabetes mellitus.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have emerged as a powerful
      approach for identifying susceptibility loci associated with polygenetic diseases
      such as type 2 diabetes mellitus (T2DM). However, it is still a daunting task to
      prioritize single nucleotide polymorphisms (SNPs) from GWAS for further
      replication in different population. Several recent studies have shown that
      genetic variation often affects gene-expression at proximal (cis) as well as
      distal (trans) genomic locations by different mechanisms such as altering rate of
      transcription or splicing or transcript stability. METHODS: To prioritize SNPs
      from GWAS, we combined results from two GWAS related to T2DM, the Diabetes
      Genetics Initiative (DGI) and the Wellcome Trust Case Control Consortium (WTCCC),
      with genome-wide expression data from pancreas, adipose tissue, liver and
      skeletal muscle of individuals with or without T2DM or animal models thereof to
      identify T2DM susceptibility loci. RESULTS: We identified 1,170 SNPs associated
      with T2DM with P < 0.05 in both GWAS and 243 genes that were located in the
      vicinity of these SNPs. Out of these 243 genes, we identified 115 differentially
      expressed in publicly available gene expression profiling data. Notably five of
      them, IGF2BP2, KCNJ11, NOTCH2, TCF7L2 and TSPAN8, have subsequently been shown to
      be associated with T2DM in different populations. To provide further validation
      of our approach, we reversed the approach and started with 26 known SNPs
      associated with T2DM and related traits. We could show that 12 (57%) (HHEX,
      HNF1B, IGF2BP2, IRS1, KCNJ11, KCNQ1, NOTCH2, PPARG, TCF7L2, THADA, TSPAN8 and
      WFS1) out of 21 genes located in vicinity of these SNPs were showing aberrant
      expression in T2DM from the gene expression profiling studies. CONCLUSIONS:
      Utilizing of gene expression profiling data from different tissues of individuals
      with or without T2DM or animal models thereof is a powerful tool for prioritizing
      SNPs from WGAS for further replication studies.

PMID- 20043854
TI  - A computational approach to resolve cell level contributions to early glandular
      epithelial cancer progression.
AB  - BACKGROUND: Three-dimensional (3D) embedded cell cultures provide an appropriate
      physiological environment to reconstruct features of early glandular epithelial
      cancer. Although these are orders of magnitude simpler than tissues, they too are
      complex systems that have proven challenging to understand. We used agent-based,
      discrete event simulation modeling methods to build working hypotheses of
      mechanisms of epithelial 3D culture phenotype and early cancer progression.
      Starting with an earlier software analogue, we validated an improved in silico
      epithelial analogue (ISEA) for cardinal features of a normally developed MDCK
      cyst. A set of axiomatic operating principles defined simulated cell actions. We
      explored selective disruption of individual simulated cell actions. New framework
      features enabled recording detailed measures of ISEA cell activities and
      morphology. RESULTS: Enabled by a small set of cell operating principles, ISEA
      cells multiplied and self-organized into cyst-like structures that mimicked those
      of MDCK cells in a 3D embedded cell culture. Selective disruption of "anoikis" or
      directional cell division caused the ISEA to develop phenotypic features
      resembling those of in vitro tumor reconstruction models and cancerous tissues in
      vivo. Disrupting either process, or both, altered cell activity patterns that
      resulted in morphologically similar outcomes. Increased disruption led to a
      prolonged presence of intraluminal cells. CONCLUSIONS: ISEA mechanisms,
      behaviors, and morphological properties may have biological counterparts. To the
      extent that in silico-to-in vitro mappings are valid, the results suggest
      plausible, additional mechanisms of in vitro cancer reconstruction or reversion,
      and raise potentially significant implications for early cancer diagnosis based
      on histology. Further ISEA development and use are expected to provide a viable
      platform to complement in vitro methods for unraveling the mechanistic basis of
      epithelial morphogenesis and cancer progression.

PMID- 20043855
TI  - Conservation of intron and intein insertion sites: implications for life
      histories of parasitic genetic elements.
AB  - BACKGROUND: Inteins and introns are genetic elements that are removed from
      proteins and RNA after translation or transcription, respectively. Previous
      studies have suggested that these genetic elements are found in conserved parts
      of the host protein. To our knowledge this type of analysis has not been done for
      group II introns residing within a gene. Here we provide quantitative statistical
      support from an analyses of proteins that host inteins, group I introns, group II
      introns and spliceosomal introns across all three domains of life. RESULTS: To
      determine whether or not inteins, group I, group II, and spliceosomal introns are
      found preferentially in conserved regions of their respective host protein,
      conservation profiles were generated and intein and intron positions were mapped
      to the profiles. Fisher's combined probability test was used to determine the
      significance of the distribution of insertion sites across the conservation
      profile for each protein. For a subset of studied proteins, the conservation
      profile and insertion positions were mapped to protein structures to determine if
      the insertion sites correlate to regions of functional activity. All inteins and
      most group I introns were found to be preferentially located within conserved
      regions; in contrast, a bacterial intein-like protein, group II and spliceosomal
      introns did not show a preference for conserved sites. CONCLUSIONS: These
      findings demonstrate that inteins and group I introns are found preferentially in
      conserved regions of their respective host proteins. Homing endonucleases are
      often located within inteins and group I introns and these may facilitate
      mobility to conserved regions. Insertion at these conserved positions decreases
      the chance of elimination, and slows deletion of the elements, since removal of
      the elements has to be precise as not to disrupt the function of the protein.
      Furthermore, functional constrains on the targeted site make it more difficult
      for hosts to evolve immunity to the homing endonuclease. Therefore, these
      elements will better survive and propagate as molecular parasites in conserved
      sites. In contrast, spliceosomal introns and group II introns do not show
      significant preference for conserved sites and appear to have adopted a different
      strategy to evade loss.

PMID- 20043856
TI  - The influence of coughing on cerebrospinal fluid pressure in an in vitro
      syringomyelia model with spinal subarachnoid space stenosis.
AB  - BACKGROUND: The influence of coughing, on the biomechanical environment in the
      spinal subarachnoid space (SAS) in the presence of a cerebrospinal fluid flow
      stenosis, is thought to be an important etiological factor in craniospinal
      disorders, including syringomyelia (SM), Chiari I malformation, and
      hydrocephalus. The aim of this study was to investigate SAS and syrinx pressures
      during simulated coughing using in vitro models and to provide information for
      the understanding of the craniospinal fluid system dynamics to help develop
      better computational models. METHODS: Four in vitro models were constructed to be
      simplified representations of: 1) non-communicating SM with spinal SAS stenosis;
      2) non-communicating SM due to spinal SAS stenosis with a distensible spinal
      column; 3) non-communicating SM post surgical removal of a spinal SAS stenosis;
      and 4) a spinal SAS stenosis due to spinal trauma. All of the models had a
      flexible spinal cord. To simulate coughing conditions, an abrupt CSF pressure
      pulse (~ 5 ms) was imposed at the caudal end of the spinal SAS by a computer
      controlled pump. Pressure measurements were obtained at 4 cm intervals along the
      spinal SAS and syrinx using catheter tip transducers. RESULTS: Pressure
      measurements during a simulated cough, showed that removal of the stenosis was a
      key factor in reducing pressure gradients in the spinal SAS. The presence of a
      stenosis resulted in a caudocranial pressure drop in the SAS, whereas pressure
      within the syrinx cavity varied little caudocranially. A stenosis in the SAS
      caused the syrinx to balloon outward at the rostral end and be compressed at the
      caudal end. A >90% SAS stenosis did not result in a significant Venturi effect.
      Increasing compliance of the spinal column reduced forces acting on the spinal
      cord. The presence of a syrinx in the cord when there was a stenosis in the SAS,
      reduced pressure forces in the SAS. Longitudinal pressure dissociation acted to
      suck fluid and tissue caudocranially in the SAS with a stenosis. CONCLUSIONS:
      Pressures in the spinal SAS during a simulated cough in vitro had similar peak,
      transmural, and longitudinal pressures to in vivo measurements reported in the
      literature. The pressure wave velocities and pressure gradients during coughing
      (longitudinal pressure dissociation and transmural pressure) were impacted by
      alterations in geometry, compliance, and the presence of a syrinx and/or
      stenosis.

PMID- 20043857
TI  - Improving the efficiency of genomic loci capture using oligonucleotide arrays for
      high throughput resequencing.
AB  - BACKGROUND: The emergence of next-generation sequencing technology presents
      tremendous opportunities to accelerate the discovery of rare variants or
      mutations that underlie human genetic disorders. Although the complete sequencing
      of the affected individuals' genomes would be the most powerful approach to
      finding such variants, the cost of such efforts make it impractical for routine
      use in disease gene research. In cases where candidate genes or loci can be
      defined by linkage, association, or phenotypic studies, the practical sequencing
      target can be made much smaller than the whole genome, and it becomes critical to
      have capture methods that can be used to purify the desired portion of the genome
      for shotgun short-read sequencing without biasing allelic representation or
      coverage. One major approach is array-based capture which relies on the ability
      to create a custom in-situ synthesized oligonucleotide microarray for use as a
      collection of hybridization capture probes. This approach is being used by our
      group and others routinely and we are continuing to improve its performance.
      RESULTS: Here, we provide a complete protocol optimized for large aggregate
      sequence intervals and demonstrate its utility with the capture of all predicted
      amino acid coding sequence from 3,038 human genes using 241,700 60-mer
      oligonucleotides. Further, we demonstrate two techniques by which the efficiency
      of the capture can be increased: by introducing a step to block cross
      hybridization mediated by common adapter sequences used in sequencing library
      construction, and by repeating the hybridization capture step. These improvements
      can boost the targeting efficiency to the point where over 85% of the mapped
      sequence reads fall within 100 bases of the targeted regions. CONCLUSIONS: The
      complete protocol introduced in this paper enables researchers to perform
      practical capture experiments, and includes two novel methods for increasing the
      targeting efficiency. Coupled with the new massively parallel sequencing
      technologies, this provides a powerful approach to identifying disease-causing
      genetic variants that can be localized within the genome by traditional methods.

PMID- 20043858
TI  - Attitude and use of herbal medicines among pregnant women in Nigeria.
AB  - BACKGROUND: The use of herbal medicines among pregnant women in Nigeria has not
      been widely studied. METHODS: Opinion of 595 pregnant women in three geopolitical
      zones in Nigeria on the use of herbal medicines, safety on usage, knowledge of
      potential effects of herbal remedies on the fetus and potential benefits or harms
      that may be derived from combining herbal remedies with conventional therapies
      were obtained using a structured questionnaire between September 2007 and March
      2008. Descriptive statistics and Fisher's exact tests were used at 95% confidence
      level to evaluate the data obtained. Level of significance was set at p<0.05.
      RESULTS: More than two-third of respondents [67.5%] had used herbal medicines in
      crude forms or as pharmaceutical prepackaged dosage forms, with 74.3% preferring
      self-prepared formulations. Almost 30% who were using herbal medicine at the time
      of the study believed that the use of herbal medicines during pregnancy is safe.
      Respondents' reasons for taking herbal medications were varied and included
      reasons such as herbs having better efficacy than conventional medicines [22.4%],
      herbs being natural, are safer to use during pregnancy than conventional
      medicines [21.1%], low efficacy of conventional medicines [19.7%], easier access
      to herbal medicines [11.2%], traditional and cultural belief in herbal medicines
      to cure many illnesses [12.5%], and comparatively low cost of herbal medicines
      [5.9%]. Over half the respondents, 56.6% did not support combining herbal
      medicines with conventional drugs to forestall drug-herb interaction. About 33.4%
      respondents believed herbal medicines possess no adverse effects while 181
      [30.4%] were of the opinion that adverse/side effects of some herbal medicines
      could be dangerous. Marital status, geopolitical zones, and educational
      qualification of respondents had statistically significant effects on respondents
      views on side effects of herbal medicines [p<0.05)] while only geopolitical zones
      and educational qualifications seemed to have influence on respondents' opinion
      on the harmful effects of herbal medicines to the fetus [p<0.05]. CONCLUSION: The
      study emphasized the wide spread use of herbal medicines by pregnant women in
      Nigeria highlighting an urgent need for health care practitioners and other
      health care givers to be aware of this practice and make efforts in obtaining
      information about herb use during ante-natal care. This will help forestall
      possible interaction between herbal and conventional medicines.

PMID- 20043860
TI  - Detection of gene pathways with predictive power for breast cancer prognosis.
AB  - BACKGROUND: Prognosis is of critical interest in breast cancer research.
      Biomedical studies suggest that genomic measurements may have independent
      predictive power for prognosis. Gene profiling studies have been conducted to
      search for predictive genomic measurements. Genes have the inherent pathway
      structure, where pathways are composed of multiple genes with coordinated
      functions. The goal of this study is to identify gene pathways with predictive
      power for breast cancer prognosis. Since our goal is fundamentally different from
      that of existing studies, a new pathway analysis method is proposed. RESULTS: The
      new method advances beyond existing alternatives along the following aspects.
      First, it can assess the predictive power of gene pathways, whereas existing
      methods tend to focus on model fitting accuracy only. Second, it can account for
      the joint effects of multiple genes in a pathway, whereas existing methods tend
      to focus on the marginal effects of genes. Third, it can accommodate multiple
      heterogeneous datasets, whereas existing methods analyze a single dataset only.
      We analyze four breast cancer prognosis studies and identify 97 pathways with
      significant predictive power for prognosis. Important pathways missed by
      alternative methods are identified. CONCLUSIONS: The proposed method provides a
      useful alternative to existing pathway analysis methods. Identified pathways can
      provide further insights into breast cancer prognosis.

PMID- 20043859
TI  - Multimodal surface-based morphometry reveals diffuse cortical atrophy in
      traumatic brain injury.
AB  - BACKGROUND: Patients with traumatic brain injury (TBI) often present with
      significant cognitive deficits without corresponding evidence of cortical damage
      on neuroradiological examinations. One explanation for this puzzling observation
      is that the diffuse cortical abnormalities that characterize TBI are difficult to
      detect with standard imaging procedures. Here we investigated a patient with
      severe TBI-related cognitive impairments whose scan was interpreted as normal by
      a board-certified radiologist in order to determine if quantitative neuroimaging
      could detect cortical abnormalities not evident with standard neuroimaging
      procedures. METHODS: Cortical abnormalities were quantified using multimodal
      surfaced-based morphometry (MSBM) that statistically combined information from
      high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values
      of cortical anatomy and cortical and pericortical DTI properties were quantified
      in a population of 43 healthy control subjects. Corresponding measures from the
      patient were obtained in two independent imaging sessions. These data were
      quantified using both the average values for each lobe and the measurements from
      each point on the cortical surface. The results were statistically analyzed as z
      scores from the mean with a p < 0.05 criterion, corrected for multiple
      comparisons. False positive rates were verified by comparing the data from each
      control subject with the data from the remaining control population using
      identical statistical procedures. RESULTS: The TBI patient showed significant
      regional abnormalities in cortical thickness, gray matter diffusivity and
      pericortical white matter integrity that replicated across imaging sessions.
      Consistent with the patient's impaired performance on neuropsychological tests of
      executive function, cortical abnormalities were most pronounced in the frontal
      lobes. CONCLUSIONS: MSBM is a promising tool for detecting subtle cortical
      abnormalities with high sensitivity and selectivity. MSBM may be particularly
      useful in evaluating cortical structure in TBI and other neurological conditions
      that produce diffuse abnormalities in both cortical structure and tissue
      properties.

PMID- 20043861
TI  - No association of the polymorphisms of the frizzled-related protein gene with
      peak bone mineral density in Chinese nuclear families.
AB  - BACKGROUND: The Wnt/beta-catenin signaling pathway plays an important role in
      skeletal development. Polymorphisms of frizzled-related protein (FRZB), an
      antagonist of this pathway, may generate variations in bone mineral density
      (BMD). In this study, we analyzed the association between FRZB genotypes and peak
      BMD variation in the spines and hips of two relatively large samples of Chinese
      female-offspring and male-offspring nuclear families. METHODS: We recruited 1,260
      subjects from 401 female-offspring nuclear families and 1,296 subjects from 427
      male-offspring nuclear families and genotyped four tagging single nucleotide
      polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning
      the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip
      osteoarthritis, were not selected in this study because of their low minor allele
      frequencies (MAFs) in Chinese people. The quantitative transmission
      disequilibrium test (QTDT) was used to analyze the association between each SNP
      and haplotype with peak BMD in female- and male-offspring nuclear families.
      RESULTS: In the female-offspring nuclear families, we found no evidence of an
      association between either single SNPs or haplotypes and peak BMD in the spine or
      hip. In the male-offspring nuclear families, no within-family association was
      observed for either SNPs or haplotypes, although a significant total association
      was found between rs4666865 and spine BMD (P = 0.0299). CONCLUSION: Our results
      suggest that natural variation in FRZB is not a major contributor to the observed
      variability in peak BMD in either Chinese females or males. Because ethnic
      differences in the FRZB genotypes may exist, other studies in different
      population are required to confirm such results.

PMID- 20043862
TI  - Status of implementation of Framework Convention on Tobacco Control (FCTC) in
      Ghana: a qualitative study.
AB  - BACKGROUND: The Framework Convention on Tobacco Control (FCTC), a World Health
      Organization treaty, has now been ratified by over 165 countries. However there
      are concerns that implementing the Articles of the treaty may prove difficult,
      particularly in the developing world. In this study we have used qualitative
      methods to explore the extent to which the FCTC has been implemented in Ghana, a
      developing country that was 39th to ratify the FCTC, and identify barriers to
      effective FCTC implementation in low income countries. METHODS: Semi-structured
      interviews with 20 members of the national steering committee for tobacco control
      in Ghana, the official multi-disciplinary team with responsibility for tobacco
      control advocacy and policy formulation, were conducted. The Framework method for
      analysis and NVivo software were used to identify key issues relating to the
      awareness of the FCTC and the key challenges and achievements in Ghana to date.
      RESULTS: Interviewees had good knowledge of the content of the FCTC, and reported
      that although Ghana had no explicitly written policy on tobacco control, the
      Ministry of Health had issued several tobacco control directives before and since
      ratification. A national tobacco control bill has been drafted but has not been
      implemented. Challenges identified included the absence of a legal framework for
      implementing the FCTC, and a lack of adequate resources and prioritisation of
      tobacco control efforts, leading to slow implementation of the treaty.
      CONCLUSION: Whilst Ghana has ratified the FCTC, there is an urgent need for
      action to pass a national tobacco control bill into law to enable it to implement
      the treaty, sustain tobacco control efforts and prevent Ghana's further
      involvement in the global tobacco epidemic.

PMID- 20043863
TI  - Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured
      with PCR genotyping of the merozoite surface protein 1 and 2.
AB  - BACKGROUND: The genetic diversity of Plasmodium falciparum has been extensively
      studied in various parts of the world. However, limited data are available from
      Pakistan. This study aimed to establish molecular characterization of P.
      falciparum field isolates in Pakistan measured with two highly polymorphic
      genetic markers, i.e. the merozoite surface protein 1 (msp-1)and 2 (msp-2).
      METHODS: Between October 2005 and October 2007, 244 blood samples from patients
      with symptomatic blood-slide confirmed P. falciparum mono-infections attending
      the Aga Khan University Hospital, Karachi, or its collection units located in
      Sindh and Baluchistan provinces, Pakistan were collected. The genetic diversity
      of P. falciparum was analysed by length polymorphism following gel
      electrophoresis of DNA products from nested polymerase chain reactions (PCR)
      targeting block 2 of msp-1 and block 3 of msp-2, including their respective
      allelic families KI, MAD 20, RO33, and FC27, 3D7/IC. RESULTS: A total of 238/244
      (98%) patients had a positive PCR outcome in at least one genetic marker; the
      remaining six were excluded from analysis. A majority of patients had monoclonal
      infections. Only 56/231 (24%) and 51/236 (22%) carried multiple P. falciparum
      genotypes in msp-1 and msp-2, respectively. The estimated total number of
      genotypes was 25 msp-1 (12 KI; 8 MAD20; 5 RO33) and 33 msp-2 (14 FC27; 19
      3D7/IC). CONCLUSIONS: This is the first report on molecular characterization of
      P. falciparum field isolates in Pakistan with regards to multiplicity of
      infection. The genetic diversity and allelic distribution found in this study is
      similar to previous reports from India and Southeast Asian countries with low
      malaria endemicity.

PMID- 20043864
TI  - Enhancing ATP-based bacteria and biofilm detection by enzymatic pyrophosphate
      regeneration.
AB  - The manufacturing processes of many electronic and medical products demand the
      use of high-quality water. Hence the water supply systems for these processes are
      required to be examined regularly for the presence of microorganisms and
      microbial biofilms. Among commonly used bacteria detection approaches, the ATP
      luminescence assay is a rapid, sensitive, and easy to perform method. The aim of
      this study is to investigate whether ATP regeneration from inorganic
      pyrophosphate, a product of the ATP luminescence assay, can stabilize the
      bioluminescence signals in ATP detection. ADPglc pyrophosphorylase (AGPPase),
      which catalyzes the synthesis of ATP from PP(i) in the presence of ADPglc, was
      selected because the system yields much lower luminescence background than the
      commercially available ATP sulfurylase/adenosine 5'-phosphosulfate (APS) system
      which was broadly used in pyrosequencing technology. The AGPPase-based assay
      could be used to measure both PP(i) and ATP quantitatively and shows 1.5- to 4.0
      fold slight increases in a 10-min assay. The method could also be used to
      stabilize the luminescence signals in detection of Escherichia coli, Pseudomonas
      aeruginosa, and Bacillus cereus in either broth or biofilm. These findings
      suggest that the AGPPase-based ATP regeneration system will find many practical
      applications such as detection of bacterial biofilm in water pipelines.

PMID- 20043865
TI  - Linoleate 9R-dioxygenase and allene oxide synthase activities of Aspergillus
      terreus.
AB  - Oxygenation of linoleic acid by Aspergillus terreus was studied with LC-MS/MS.
      9(R)-Hydroperoxy-10(E),12(Z)-octadecadienoic acid (9R-HpODE) was identified along
      with 10(R)-hydroxy-8(E),12(Z)-octadecadienoic acid and variable amounts of 8(R)
      hydroxy-9(Z),12(Z)-octadecadienoic acid. 9R-HpODE was formed from [11S-2H]18:2n-6
      with loss of the deuterium label, suggesting antarafacial hydrogen abstraction
      and oxygenation. Two polar metabolites were identified as 9-hydroxy-10-oxo-12(Z)
      octadecenoic acid (alpha-ketol) and 13-hydroxy-10-oxo-11(E)-octadecenoic acid
      (gamma-ketol), likely formed by spontaneous hydrolysis of an unstable allene
      oxide, 9(R),10-epoxy-10,12(Z)-octadecadienoic acid. alpha-Linolenic acid and
      20:2n-6 were oxidized to hydroperoxy fatty acids at C-9 and C-11, respectively,
      but alpha- and gamma-ketols of these fatty acids could not be detected. The
      genome of A. terreus lacks lipoxygenases, but contains genes homologous to 5,8
      linoleate diol synthases and linoleate 10R-dioxygenases of aspergilli. Our
      results demonstrate that linoleate 9R-dioxygenase linked to allene oxide synthase
      activities can be expressed in fungi.

PMID- 20043866
TI  - Role of loop 9 on the function of neuronal nicotinic receptors.
AB  - We have studied the role of loop 9 in the function of neuronal nicotinic
      receptors. By systematically mutating the residues in the loop we have determined
      that the most important amino acids determining the coupling of binding to gating
      are the ones closer to the transmembrane region. Single mutations at location
      E173 in homomeric alpha7 receptors destroyed their function by completely
      abolishing the current while preserving the expression at the membrane. In
      contrast, heteromeric receptor alpha3beta4 with the same mutations retained some
      function. We conclude that loop 9 has a different role in the function of
      homomeric and heteromeric receptors.

PMID- 20043867
TI  - The in vivo performance of bioartificial pancreas in bone marrow cavity: a case
      report of a spontaneous diabetic feline.
AB  - Recent studies reported that bone marrow cavity offers a widely distributed and
      well-vascularized microenvironment which is a considerable implantation site for
      bioartificial pancreas (BAP). In this study, the in vivo performance of BAPs in
      bone marrow was further demonstrated in a spontaneous diabetes animal. Mouse
      insulinoma cells encapsulating in agarose gel were enclosed in a calcium
      phosphate cement chamber to create a BAP. Ten BAPs were implanted into the femur
      bone marrow cavity of a diabetic feline. The preprandial blood glucose level, 2 h
      glucose curve, serum C-peptide level and physiological conditions of the
      recipient were recorded perioperatively. Results showed that the cat still
      suffered from hyperglycemia postoperatively. However, the physiological
      conditions of feline were improved with an increase of serum C-peptide level. The
      peak point of 2 h glucose curve decreased from 400 to 165-290 mg/dl. The
      efficiency of exogenous insulin extended from 2 to 10-14 h postoperatively which
      reveals that the implanted BAPs had partial function. This case report revealed
      that BAPs implanted in the bone marrow cavity for the spontaneous diabetic is
      effective. The implanted BAPs provided therapeutic benefit despite sustained
      hyperglycemia. Further study shall be considered to improve the outcomes of BAPs
      transplantation.

PMID- 20043868
TI  - Stabilization and translocation of p53 to mitochondria is linked to Bax
      translocation to mitochondria in simvastatin-induced apoptosis.
AB  - Statins are cholesterol-lowing drugs with pleiotropic effects including
      cytotoxicity to cancer cells. In this study, we investigated the signaling
      pathways leading to apoptosis by simvastatin. Simvastatin induced cardinal
      features of apoptosis including increased DNA fragmentation, disruption of
      mitochondrial membrane potential (MMP), and increased caspase-3 activity by
      depleting isoprenoids in MethA fibrosarcoma cells. Interestingly, the simvastatin
      induced apoptosis was accompanied by p53 stabilization involving Mdm2
      degradation. The apoptosis was ameliorated in p53 knockdown clones of MethA cells
      as well as p53(-/-) HCT116 cells. The stabilized p53 protein translocated to
      mitochondria with Bax, and cytochrome c was released into cytosol. Moreover,
      knockdown or deficiency of p53 expression reduced both Bax translocation to
      mitochondria and MMP disruption in simvastatin-induced apoptosis. Taken together,
      these all indicate that stabilization and translocation of p53 to mitochondria is
      involved in Bax translocation to mitochondria in simvastatin-induced apoptosis.

PMID- 20043869
TI  - Negative charge of the glutamic acid 417 residue is crucial for isomerohydrolase
      activity of RPE65.
AB  - RPE65 is the isomerohydrolase essential for regeneration of 11-cis retinal, the
      chromophore of visual pigments. Here we compared the impacts of two mutations in
      RPE65, E417Q identified in patients with Leber congenital amaurosis (LCA), and
      E417D on isomerohydrolase activity. Although both mutations decreased the
      stability of RPE65 and altered its sub-cellular localization, E417Q abolished
      isomerohydrolase activity whereas the E417D mutant retained partial enzymatic
      activity suggesting that the negative charge of E417 is important for RPE65
      catalytic activity. Loss of charge at this position may represent a mechanism by
      which the E417Q mutation causes blindness in LCA patients.

PMID- 20043870
TI  - Induction of TAp63 by histone deacetylase inhibitors.
AB  - TAp63 belongs to the p53-tumour suppressor family and is capable of
      transactivating a set of target genes to induce cell cycle arrest and apoptosis.
      We showed that treatment of cancer cells with chemo-therapeutic drugs or the
      histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) results in induction of
      TAp63 expression, which is in turn related with chemosensitivity. Indeed,
      induction of TAp63 by TSA affects sensitivity to chemo-therapeutic drugs via the
      cleavage of the trans-inhibitory domain of TAp63 by active caspases, resulting in
      generation of a transcriptionally hyper-active TAp63 fragment. Therefore
      therapeutic approaches that enhance TAp63 expression may offer an improvement in
      the management of chemoresistant tumours. In this study we tested the abilities
      of different HDAC inhibitors to induce TAp63 expression. We discovered that two
      HDAC inhibitors belonging to the hydroxamate group, namely TSA and LBH589, are
      the most efficient inducers of TAp63 expression. Finally, we found that induction
      of TAp63 expression in HCT116 cells depends on p53, as p53-negative HCT116 cells
      failed to induce significant TAp63 expression following treatment with different
      HDAC inhibitors.

PMID- 20043871
TI  - Tumor necrosis factor-alpha accelerates apoptosis of steatotic hepatocytes from a
      murine model of non-alcoholic fatty liver disease.
AB  - Non-alcoholic steatohepatitis (NASH) develops in a subset of patients with non
      alcoholic fatty liver disease (NAFLD), but the exact mechanisms involved in the
      progression of NAFLD to NASH remain poorly understood. We investigated the role
      of tumor necrosis factor-alpha (TNF-alpha) in the apoptosis of hepatocytes that
      is related to the severity of NASH. We separated primary hepatocytes from the
      NAFLD liver caused by a high-fat diet. The production of intracellular reactive
      oxygen species was increased in steatotic hepatocytes, which were also sensitive
      to TNF-alpha. This factor induced significant apoptosis through the signal
      regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) pathway. We describe
      here a novel culture model of steatotic hepatocytes separated from the NAFLD
      liver, and demonstrate that TNF-alpha induces their apoptosis in vitro.

PMID- 20043872
TI  - The acute phase response stimulates the expression of angiopoietin like protein
      4.
AB  - The acute phase response is characterized by elevations in serum triglyceride
      levels due to both an increase in hepatic VLDL production and a delay in the
      clearance of triglyceride rich lipoproteins secondary to a decrease in
      lipoprotein lipase (LPL) activity. Recently there has been a marked increase in
      our understanding of factors that regulate LPL activity. GPIHBP1 facilitates the
      interaction of LPL and lipoproteins thereby allowing lipolysis to occur.
      Angiopoietin like proteins (ANGPTL) 3 and 4 inhibit LPL activity. In the present
      study, treatment of mice with LPS, an activator of TLR4 and a model of Gram
      negative infections, did not alter the expression of GPIHBP1 in heart or adipose
      tissue. However, LPS decreased the expression of ANGPTL3 in liver and increased
      the expression of ANGPTL4 in heart, muscle, and adipose tissue. Serum ANGPTL4
      protein levels were markedly increased at 8 and 16h following LPS treatment.
      Administration of zymosan, an activator of TLR2 and a model of fungal infections,
      also increased serum ANGPTL4 protein and mRNA levels in liver, heart, muscle, and
      adipose tissue. Finally, treatment of 3T3-L1 adipocytes with LPS or cytokines
      (TNF alpha, IL-1 beta, and interferon gamma) stimulated ANGPTL4 expression. These
      studies demonstrate that ANGPTL4 is a positive acute phase protein and the
      increase in ANGPTL4 could contribute to the hypertriglyceridemia that
      characteristically occurs during the acute phase response by inhibiting LPL
      activity.

PMID- 20043873
TI  - Muscle cells enhance resistance to pro-inflammatory cytokine-induced cartilage
      destruction.
AB  - Pro-inflammatory cytokines IL-1beta and TNFalpha play important roles in the
      manifestation of arthritis by disrupting the anabolic and catabolic activities of
      the chondrocytes. We observed a novel mechanism of cartilage regulation by which
      muscle cells diminish the response of chondrocytes to IL-1beta and TNFalpha. We
      found that chondrocytes cocultured with muscle cells or cultured in muscle cell
      conditioned medium significantly enhanced the expression of cartilage matrix
      proteins (collagen II and collagen IX) and resisted IL-1beta and TNFalpha-induced
      cartilage damage. Our data suggest that this effect is achieved by inhibiting the
      expression of key components of the signaling pathways of pro-inflammatory
      cytokines (including NFkappaB, ESE-1, Cox-2, and GADD45beta), leading to
      attenuated expression of cartilage-degrading enzymes (MMPs and ADAMTS4).
      Therefore, our work unveils a potential role of muscle in regulating cartilage
      homeostasis and response to pro-inflammatory stimuli, and provides insights on
      designing treatment strategies for joint degenerative diseases such as arthritis.

PMID- 20043874
TI  - Sclerostin binds and regulates the activity of cysteine-rich protein 61.
AB  - Sclerostin, a secreted glycoprotein, regulates osteoblast function. Using yeast
      two-hybrid and direct protein interaction analyses, we demonstrate that
      sclerostin binds the Wnt-modulating and Wnt-modulated, extracellular matrix
      protein, cysteine-rich protein 61 (Cyr61, CCN1), which regulates mesenchymal stem
      cell proliferation and differentiation, osteoblast and osteoclast function, and
      angiogenesis. Sclerostin was shown to inhibit Cyr61-mediated fibroblast
      attachment, and Cyr61 together with sclerostin increases vascular endothelial
      cell migration and increases osteoblast cell division. The data show that
      sclerostin binds to and influences the activity of Cyr61.

PMID- 20043875
TI  - Fyn kinase controls FcepsilonRI receptor-operated calcium entry necessary for
      full degranulation in mast cells.
AB  - IgE-antigen-dependent crosslinking of the high affinity IgE receptor
      (FcepsilonRI) on mast cells leads to degranulation, leukotriene synthesis and
      cytokine production. Calcium (Ca(2+)) mobilization is a sine qua non requisite
      for degranulation, allowing the rapid secretion of stored pro-inflammatory
      mediators responsible for allergy symptoms. Fyn is a Src-family kinase that
      positively controls FcepsilonRI-induced mast cell degranulation. However, our
      understanding of the mechanism connecting Fyn activation to secretion of pre
      synthesized mediators is very limited. We analyzed FcepsilonRI-dependent Ca(2+)
      mobilization in bone marrow-derived mast cells (BMMCs) differentiated from WT and
      Fyn -/- knock out mice. Fyn -/- BMMCs showed a marked defect in extracellular
      Ca(2+) influx after FcepsilonRI crosslinking but not after thapsigargin addition.
      High concentrations of Gadolinium (Gd(3+)) partially blocked FcepsilonRI-induced
      Ca(2+) influx in WT cells but, in contrast, completely inhibited Ca(2+)
      mobilization in Fyn -/- cells. Low concentrations of an inhibitor of the
      canonical transient receptor potential (TRPC) Ca(2+) channels (2
      aminoethoxyphenyl-borane, 2-APB) blocked FcepsilonRI-induced maximal Ca(2+) rise
      in WT but not in Fyn -/- cells. Ca(2+) entry through Fyn-controlled, 2-APB
      sensitive channels was found to be important for full degranulation and IL-2 mRNA
      accumulation in WT cells. Immunoprecipitation assays showed that Fyn kinase
      interacts with TRPC 3/6/7 channels after IgE-antigen stimulation, but its
      association is not related to protein tyrosine phosphorylation. Results indicate
      Fyn kinase mediates the receptor-dependent activation of TRPC channels that
      contribute to degranulation in FcepsilonRI-stimulated mast cells.

PMID- 20043876
TI  - Identification of a Protein Kinase C-dependent phosphorylation site involved in
      sensitization of TRPV4 channel.
AB  - Transient Receptor Potential (TRP) proteins are non-selective cation channels
      performing diverse cellular functions. TRPV1 and TRPV4, two calcium-permeable
      channels of the vanilloid subfamily of TRP proteins, are activated by various
      physical and chemical stimuli, including noxious heat and mechanical stress,
      respectively. These channels are also required for exaggerated sensation of
      painful stimuli, condition referred to as hyperalgesia, which is frequently
      associated with inflammation. Phosphorylation of TRPV1, involving Protein Kinase
      C (PKC) and Protein Kinase A (PKA), appears to be the predominant mechanism for
      channel sensitization and development of heat hyperalgesia. PKC and PKA pathways
      have also been implicated in the sensitization of TRPV4, but the respective
      phosphorylation sites remain unknown. Using mass spectrometry, we report now that
      TRPV4 is phosphorylated on serine 824 by the PKC-activating phorbol 12-myristate
      13-acetate. This phosphorylation is prevented by a PKC inhibitor, confirming the
      involvement of PKC. Ser824, located in the carboxy-terminal cytosolic tail of
      TRPV4, is also phosphorylated after activation of the PKA pathway by forskolin,
      albeit less potently. Substitution of Ser824 with aspartic acid, mimicking
      phosphorylation at this site, increased TRPV4-mediated calcium influx in resting
      and in stimulated cells, underlining the importance of this residue in TRPV4
      regulation. Thus PKC, and possibly PKA, phosphorylate TRPV4 at Ser824 leading to
      the enhancement of TRPV4 channel function. Our findings suggest an important role
      of this phosphorylation in TRPV4 sensitization and the development of
      hyperalgesia.

PMID- 20043877
TI  - Structural characterization of the bifunctional glucanase-xylanase CelM2 reveals
      the metal effect and substrate-binding moiety.
AB  - The bifunctional glycoside hydrolase enzyme, CelM2, is able to hydrolyze glucan
      and xylan effectively. The crystal structure of this protein has been determined,
      providing useful sequential and structural information [K.H. Nam, S.J. Kim, K.Y.
      Hwang, Crystal structure of CelM2, a bifunctional glucanase-xylanase protein from
      a metagenome library, Biochem. Biophys. Res. Commun. 383 (2009) 183-186]. In
      addition, this protein is a good model for understanding bifunctional enzymes,
      and it will provide information relevant for genetic engineering that will be
      useful in the design of bifunctional proteins. However, previous structural
      characterization was not sufficient to develop an understanding of the metal ion
      and substrate-binding moiety. Herein, we determined the metal-binding site of
      CelM2 using zinc ions. Our results revealed that the zinc ions participate in the
      crystallographic packing and enzyme folding of the external region of the TIM
      like barrel domain. Based on our structure, zinc ions induce the passive form of
      the CAP region at the catalytic cleft of the CelM2 protein. Moreover, glucose was
      bound to the CelM2 structure at the catalytic site. This structure provides the
      binding moiety that binds to the hydroxyl group of substrates such as cellulose.
      In addition, a structural comparison of celM2 with Cel44 provides a good model of
      the binding mode of CelM2. Thus, our study represents a novel structural
      characterization of the metal-binding site and the structure of the complex
      formed between CelM2 and its substrate.

PMID- 20043878
TI  - Identification of a new secretory factor, CCDC3/Favine, in adipocytes and
      endothelial cells.
AB  - The vascular system secretes many bioactive factors. In a gene chip database, we
      searched for novel genes with signal sequences that are specifically expressed in
      murine aorta, and focused on one gene previously named CCDC3 (NCBI nucleotide
      entry NM_028804), and we designated as Favine (fat/vessel-derived secretory
      protein). Northern blot analysis revealed that CCDC3 was expressed abundantly in
      the aorta and adipose tissues. The mRNA levels of CCDC3 were higher in adipose
      tissues of obese db/db mice than control mice, and induced during differentiation
      of rat primary adipocytes. In differentiated adipocytes, CCDC3 mRNA expression
      was enhanced by insulin and pioglitazone, a PPARgamma agonist, and suppressed by
      TNF-alpha, isoproterenol and norepinephrine. Transient expression experiments
      followed by N-terminal amino acid sequence analysis revealed secretion of CCDC3
      protein into the culture medium, which was dose-dependently reduced by brefeldin
      A, an inhibitor of Golgi-mediated secretory pathway. When expressed in COS-7
      cells, CCDC3 protein was post-transcriptionally modified with N-glycosylation,
      and formed a dimer complex. These results indicate that CCDC3 is a protein
      secreted by adipocytes and endothelial cells, and that its level is regulated
      both hormonally and nutritionally.

PMID- 20043879
TI  - Probing the roles of conserved arginine-44 of Escherichia coli dihydrofolate
      reductase in its function and stability by systematic sequence perturbation
      analysis.
AB  - Sequence perturbation analysis is a powerful method to reveal roles of an amino
      acid residue in function and stability of a protein. By using and improving this
      method, we studied roles of highly conserved Arg44 of Escherichia coli
      dihydrofolate reductase (DHFR) in its function and stability. Here, we introduced
      systematic amino acid substitutions at this position and found that all 19 kinds
      of amino acid substitutions were tolerated, but the mutations significantly
      reduced the enzymatic activity and the binding affinity toward the cofactor
      NADPH. Moreover, the mutational effects on the cofactor binding affinity were
      well correlated with those on the catalytic activity, indicating that the R44X
      mutations affect the catalytic activity mainly by modulating the cofactor binding
      affinity. On the other hand, thermal denaturation measurements showed that most
      mutations stabilized the protein. Comparison between the mutational effects and
      various amino acid indices taken from the AAindex database indicated that
      hydrophobicity and polarity are key determinants of amino acids favorable at this
      position. These results suggest that through electrostatic interactions Arg44
      plays a functional role in retaining the cofactor binding affinity at the cost of
      the protein stability.

PMID- 20043880
TI  - Methylation analyses on promoters of mPer1, mPer2, and mCry1 during perinatal
      development.
AB  - Recent studies revealed dramatic changes in circadian clock genes' expression
      during the perinatal period. In this study, we characterized DNA methylation for
      three clock genes mPer1, mPer2, and mCry1 at their selected promoter regions
      during development. Results for the suprachiasmatic nucleus (SCN) and liver (at
      embryonic day 19, postnatal day 1 and postnatal day 7) were compared to those of
      sperm. Few methylations were detected for the mPer2 and mCry1 promoters. The 3rd
      E-box region of the mPer1 promoter exhibited methylation only in sperm.
      Significant demethylation was observed in the 4th E-box region of the mPer1
      promoter between E19 and P1 in the SCN but not in liver tissue. This
      demethylation state was maintained at P7 for the SCN. Luciferase reporter assays
      using in vitro methylated promoters revealed an inhibitory effect of promoter
      methylation on mPer1 expression. The results suggested that epigenetic mechanisms
      such as DNA methylation might contribute to the developmental expression of clock
      genes.

PMID- 20043881
TI  - Cell-penetrating DNA-binding protein as a safe and efficient naked DNA delivery
      carrier in vitro and in vivo.
AB  - Non-viral gene delivery is a safe and suitable alternative to viral vector
      mediated delivery to overcome the immunogenicity and tumorigenesis associated
      with viral vectors. Using the novel, human-origin Hph-1 protein transduction
      domain that can facilitate the transduction of protein into cells, we developed a
      new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery
      system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced
      green fluorescent protein (EGFP) reporter plasmid that includes the five repeats
      of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex
      with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and
      delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully
      delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in
      mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2)
      plant cells. When 10 microg of pEGFP DNA was intranasally administered to mice
      using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout
      the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA
      delivery strategy may be an useful non-viral DNA delivery system for gene therapy
      and DNA vaccines.

PMID- 20043883
TI  - Histone H3 methylation at lysine 4 on the SLC2A5 gene in intestinal Caco-2 cells
      is involved in SLC2A5 expression.
AB  - Histone H3 methylation at lysine 4 (K4) is associated with euchromatic regions
      and is thought to be important for the transcriptional activation of genes during
      differentiation. In this study, we found that di- and tri-methylation of histone
      H3 at K4 and acetylation of histones H3 and H4 from the promoter/enhancer to the
      transcribed region close to the transcription initiation site of the solute
      carrier family 2, member 5 (SLC2A5) gene, and its expression, were induced by
      differentiation of intestine-like Caco-2 cells. These effects were accompanied by
      contact inhibition of cell growth of these cells. Furthermore, these
      modifications were induced by co-treatment with a synthetic glucocorticoid
      hormone dexamethasone and a p44/42 mitogen-activated protein kinase inhibitor
      PD89059. Our results suggest that methylation of histone H3 at K4 and acetylation
      of histones H3 and H4 are involved in SLC2A5 gene induction associated with
      intestinal differentiation of Caco-2 cells.

PMID- 20043882
TI  - The death effector domain-containing DEDD forms a complex with Akt and Hsp90, and
      supports their stability.
AB  - Insulin secretion and glucose transport are the major mechanisms to balance
      glucose homeostasis. Recently, we found that the death effector domain-containing
      DEDD inhibits cyclin-dependent kinase-1 (Cdk1) function, thereby preventing Cdk1
      dependent inhibitory phosphorylation of S6 kinase-1 (S6K1), downstream of
      phosphatidylinositol 3-kinase (PI3K), which overall results in maintenance of
      S6K1 activity. Here we newly show that DEDD forms a complex with Akt and heat
      shock protein 90 (Hsp90), and supports the stability of both proteins. Hence, in
      DEDD(-/-) mice, Akt protein levels are diminished in skeletal muscles and adipose
      tissues, which interferes with the translocation of glucose-transporter 4 (GLUT4)
      upon insulin stimulation, leading to inefficient incorporation of glucose in
      these organs. Interestingly, as for the activation of S6K1, suppression of Cdk1
      is involved in the stabilization of Akt protein by DEDD, since diminishment of
      Cdk1 in DEDD(-/-) cells via siRNA expression or treatment with a Cdk1-inhibitor,
      increases both Akt and Hsp90 protein levels. Such multifaceted involvement of
      DEDD in glucose homeostasis by supporting both insulin secretion (via maintenance
      of S6K1 activity) and glucose uptake (via stabilizing Akt protein), may suggest
      an association of DEDD-deficiency with the pathogenesis of type 2 diabetes
      mellitus.

PMID- 20043884
TI  - Antagonistic crosstalk of Wnt/beta-catenin/Bmp signaling within the Apical
      Ectodermal Ridge (AER) regulates interdigit formation.
AB  - Digit and interdigit (D/ID) development is one of the important research fields
      in molecular developmental biology. Interdigital cell death (ICD) is a
      morphogenetic event which has been considered as an essential process for D/ID
      formation. Although some growth factors including Bmp and Fgf signaling can
      modulate ICD, growth factor crosstalk regulating ICD is poorly understood. Wnt
      canonical pathway and Bmp signal crosstalk has been considered as the essential
      growth factor crosstalk in organogenesis. To elucidate the crosstalk to regulate
      the D/ID formation, we analyzed conditional mutant mice with limb bud ectoderm
      expressing constitutively activated beta-catenin signaling. We showed that
      modulation of Wnt/beta-catenin signal in the limb ectoderm including the AER
      regulates ID apoptosis. We also demonstrated that Wnt/beta-catenin signaling in
      the ectoderm can positively regulate Fgf8 possibly antagonizing the epithelial
      derived Bmp signaling. Human birth defects for digit abnormalities have been
      known to be affected by multiple parameters. Elucidation of the potential
      mechanisms underlying such D/ID development is an urgent medical issue to be
      solved. This work would be one of the first studies showing essential growth
      factor cascades in the D/ID formation.

PMID- 20043885
TI  - Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane
      permeabilization and cathepsin L activity.
AB  - Lipotoxicity, which is triggered when cells are exposed to elevated levels of
      free fatty acids, involves cell dysfunction and apoptosis and is emerging as an
      underlying factor contributing to various pathological conditions including
      disorders of the central nervous system and diabetes. We have shown that palmitic
      acid (PA)-induced lipotoxicity (PA-LTx) in nerve growth factor-differentiated
      PC12 (NGFDPC12) cells is linked to an augmented state of cellular oxidative
      stress (ASCOS) and apoptosis and that these events are inhibited by
      docosahexanoic acid (DHA). The mechanisms of PA-LTx in nerve cells are not well
      understood, but our previous findings indicate that it involves ROS generation,
      mitochondrial membrane permeabilization (MMP), and caspase activation. The
      present study used nerve growth factor differentiated PC12 cells (NGFDPC12 cells)
      and found that lysosomal membrane permeabilization (LMP) is an early event during
      PA-induced lipotoxicity that precedes MMP and apoptosis. Cathepsin L, but not
      cathepsin B, is an important contributor in this process since its
      pharmacological inhibition significantly attenuated LMP, MMP, and apoptosis. In
      addition, co-treatment of NGFDPC12 cells undergoing lipotoxicity with DHA
      significantly reduced LMP, suggesting that DHA acts by antagonizing upstream
      signals leading to lysosomal dysfunction. These results suggest that LMP is a key
      early mediator of lipotoxicity and underscore the value of interventions
      targeting upstream signals leading to LMP for the treatment of pathological
      conditions associated with lipotoxicity.

PMID- 20043886
TI  - Bursts of 15-30 Hz oscillations following noxious laser stimulus originate in
      posterior cingulate cortex.
AB  - Previous EEG studies reported the presence of synchronised 15-30 Hz oscillations
      in vertex electrodes following innocuous somatosensory stimulation and noxious
      laser stimulation. The purpose of the present study was to analyse the sources of
      poststimulus increases of 15-30 Hz oscillations during noxious laser stimulation
      of four different body regions and to compare the sources of the poststimulus
      synchronisation with the sources of the N2 component of laser-evoked potential
      (LEP). In 10 healthy subjects, moderately painful laser stimuli were applied to
      the dorsum of the right hand, dorsum of the right foot, right groin, and right
      side of the face. EEG data, recorded from 111 scalp sites, were analysed using
      event-related desynchronisation method and source dipole analysis. A profound
      amplitude increase of 15-30 Hz oscillations peaking 1-2 s after noxious laser
      stimulation was found during stimulation of each body part. The sources of these
      oscillations were located in the dorsal posterior cingulate cortex and showed no
      somatotopic arrangement. The sources of the N2-LEP component were located in the
      anterior mid-cingulate cortex 25-30 mm rostral to the sources of 15-30 Hz
      oscillations. The amplitude of the poststimulus synchronisation of 15-30 Hz
      oscillations correlated (P<0.05) with the amplitude of N2-LEP component. Results
      show that noxious laser stimuli induce bursts of 15-30 Hz oscillations in the
      posterior cingulate cortex. The poststimulus increases of 15-30 Hz oscillations
      may stand for transient cortical inhibition possibly aiding temporary suppression
      of motor programs that have been primed by noxious stimulation.

PMID- 20043887
TI  - Spinogenesis and pruning in the primary auditory cortex of the macaque monkey
      (Macaca fascicularis): an intracellular injection study of layer III pyramidal
      cells.
AB  - Recently we demonstrated that neocortical pyramidal cells in visual, visual
      association and prefrontal cortex of the macaque monkey are characterised by
      different growth, branching, spinogenesis and pruning during development. Some
      neurons, such as those in the primary visual area, prune more spines than they
      grow following sensory onset, while others such as those in area TE grow more
      than they prune. To what extent these different neuronal growth profiles may vary
      among cortical areas remains to be determined. To better comprehend the nature
      and extent of these regional differences in pyramidal cell growth profiles we
      expanded the bases for comparison by studying neurons in the primary auditory
      cortex (A1). We found that pyramidal cells in A1 continue to grow their basal
      dendritic trees beyond the peak period of spinogenesis (3(1)/(2) months) up until
      at least 7 months of age. Likewise, the most prolific branching patterns were
      observed in the dendritic trees of pyramidal cells at 7 months of age. These data
      reveal that the basal dendritic trees of cells in A1 continue to grow for a much
      longer period, and attain almost double the number of spines, as compared with
      those in V1. Such differences in the growth profiles of neocortical pyramidal
      cells among cortical areas may influence therapeutic outcomes when applying new
      technologies such as neurotrophic delivery devices or stem cell therapy.

PMID- 20043888
TI  - Monosodium glutamate neonatal treatment as a seizure and excitotoxic model.
AB  - Monosodium glutamate (MSG) subcutaneously administrated to neonatal rats induces
      several neurochemical alterations in the brain, which have been associated with
      an excitotoxic process triggered by an over activation of glutamate receptors;
      however there are few systematic studies about initial changes in
      intracerebroventricular (i.c.v.) Glu levels produced by MSG in the brain. Thus,
      to characterize these changes, rat pups were injected with a MSG solution at 1,
      3, 5 and 7 postnatal days (PD), and i.c.v. Glu levels and hippocampal total
      content of related amino acids (Asp, Glu, Gln, Gly, Tau, Ala and GABA) were
      estimated before, immediately and after each injection. Behavioral and EEG
      responses were also monitored after MSG administrations. Significant rise in
      i.c.v. Glu levels were found, mainly in response to the first and second
      injection. Moreover, the total content of all amino acids evaluated also
      increased during the first hour after the first MSG administration but only Glu
      and GABA remained elevated after 24 h. These biochemical modifications were
      accompanied with behavioral alterations characterized by: screeching, tail
      stiffness, head nodding, emprosthotonic flexion episodes and generalized tonic
      clonic convulsions, which were associated with electroencephalographic pattern
      alterations. Altered behavior found in animals treated with MSG suggests an
      initial seizure situation. Although four MSG administrations were used, the most
      relevant findings were observed after the first and second administrations at PD1
      and PD3, suggesting that only two MSG injections could be sufficient to resemble
      a seizure and/or excitotoxic model.

PMID- 20043889
TI  - Tanshinone II A down-regulates HMGB1, RAGE, TLR4, NF-kappaB expression,
      ameliorates BBB permeability and endothelial cell function, and protects rat
      brains against focal ischemia.
AB  - Inflammatory damage plays an important role in cerebral ischemic pathogenesis.
      HMGB1-induced NF-kappaB activation pathway has been gaining recognition as a key
      contributor to the proinflammatory response. Tanshinone II A (Tan II A) has been
      proved to elicit a series of biologic effects through its antiinflammatory
      property. But the mechanism underlying is poorly understood. This study evaluated
      the Tan II A's protective role in cerebral ischemia and its potential mechanism.
      Male Sprague-Dawley rats were subjected to pMCAO. Experiment 1 was used to
      evaluate the longitudinal expression of HMGB1, RAGE and TLR4 and NF-kappaB in the
      cerebral ischemia. Experiment 2 was used to detect Tan II A's neuroprotection. At
      24 h after pMCAO, neurologic deficit, brain water content and infarct size were
      measured. Immunohistochemistry, RT-PCR, Western blot and confocal microscope were
      used to analyze the expression of HMGB1, RAGE, TLR4 and NF-kappaB. Experiment 3
      was used to detect Tan II A's influence on BBB. The expressions of HMGB1, TLR4,
      RAGE and NF-kappaB were up-regulated in ischemic brain. Compared with pMCAO
      group, the expressions of these factors significantly decreased in Tan II A-H
      group, the neurologic deficit, infarct volume and brain water content were
      alleviated (P<0.05) and claudin-5 was predominantly expressed in brain
      capillaries. Tan II A protected the brain from damage caused by pMCAO; this
      effect may be through down-regulation of HMGB1, RAGE and TLR4, NF-kappaB and up
      regulation claudin-5 expression.

PMID- 20043890
TI  - A long-term observation of olfactory ensheathing cells transplantation to repair
      white matter and functional recovery in a focal ischemia model in rat.
AB  - Trials of neuroprotection in ischemic stroke mainly concern gray matter
      protection, with little information on white matter damage. Olfactory ensheathing
      cells (OECs) are capable of providing continuous neurotrophic factor and of
      promoting growth and remyelination of damaged axons. We evaluated OECs for the
      repair of white matter after transplantation in middle cerebral artery occlusion
      (MCAO) rat. OECs were cultured from the olfactory bulbs of adult green
      fluorescent protein (GFP)-expressing transgenic rats and transplanted into peri
      infarct basal ganglia imminently after reperfusion. The mortality, neurological
      score, and function were record everyday until 56 days. At 24 h and 56 days, the
      infarction volume, the Luxol-fast blue (LFB) staining, and Neurofilament (NF)
      immunohistochemistry and Western blot were performed to assess the demyelination
      and remyelination in white matter. OECs transplantation reduced the infarct
      volume, decreased mortality, and improved neurological deficits in 56 days after
      MCAO. LFB marked myelin, NF-positive immunohistochemistry, and Western blot
      indicated that the remyelination and axon regeneration in OEC transplanted rat
      were significant. In conclusion, OECs can protect the white matter from ischemic
      injury, but the potential mechanisms of transplanted OEC-mediated recovery need
      further studies to identify.

PMID- 20043892
TI  - Different striatal D2-like receptor function in an early stage after unilateral
      striatal lesion and medial forebrain bundle lesion in rats.
AB  - Unilateral striatal lesion and complete medial forebrain bundle (MFB) lesion by 6
      hydroxydopamine in rats have been widely used as Parkinson disease (PD) models.
      However, the difference of pre- and post-synaptic dopamine (DA) system in these
      two models are not well concerned. In order to investigate the pathophysiologic
      difference between the MFB lesion rats and striatal lesion rats, we studied the
      variation of pre-synaptic DA transporter and post-synaptic D(2)-like receptor in
      nigrostriatal DA system using binding assay, behavioral test and a small animal
      PET. Our data showed that there was a same tendency of the striatal DA
      transporter decrease both in MFB lesion rats and striatal lesion rats 4 weeks
      after lesion, however, it showed increase (up-regulation) of D(2)-like receptor
      in the MFB lesion rats, whereas showed decrease (down-regulation) in the striatal
      lesion rat. This finding strongly indicated the different dynamic
      pathophysiologic process between the MFB lesion model and striatal lesion model.
      MFB lesion model mimics an early stage of PD, whereas striatal lesion model
      mimics Parkinson syndrome, such as vascular Parkinson syndrome. Such difference
      should be taken into account in the selection of these model systems.

PMID- 20043893
TI  - Actions of bis(7)-tacrine and tacrine on transient potassium current in rat DRG
      neurons and potassium current mediated by K(V)4.2 expressed in Xenopus oocyte.
AB  - Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] is a dimeric AChE inhibitor derived
      from tacrine with a potential to treat Alzheimer's disease. Actions of bis(7)
      tacrine on ligand-gated ion channels and voltage-gated cation channels have been
      identified on neurons of both central and peripheral nervous systems. In the
      present study, the effect of bis(7)-tacrine was investigated on the K(V)4.2
      encoded potassium currents expressed in Xenopus oocytes and the transient A-type
      potassium current (I(K(A))) on rat DRG neurons. Bis(7)-tacrine suppressed
      recombinant Kv4.2 potassium channels in a concentration-dependent manner, with
      IC(50) value of 0.53+/-0.13 muM. Tacrine also inhibited Kv4.2 channels, but with
      a much lower potency (IC(50) 74+/-15 muM).The possible mechanisms underlying the
      inhibition on potassium currents by bis(7)-tacrine/tacrine could be that
      inactivation of the transient potassium currents was accelerated and recovery of
      the native or Kv4.2 expressed potassium currents was suppressed by bis(7)
      tacrine/tacrine.

PMID- 20043894
TI  - Restraint stress alters the secretory activity of neurons co-expressing urocortin
      1, cocaine- and amphetamine-regulated transcript peptide and nesfatin-1 in the
      mouse Edinger-Westphal nucleus.
AB  - Central stress regulatory pathways utilize various neuropeptides, such as
      urocortin-1 (Ucn1) and cocaine- and amphetamine-regulated transcript peptide
      (CART). Ucn1 is most abundantly expressed in the non-preganglionic Edinger
      Westphal nucleus (npEW). In addition to Ucn1, CART and nesfatin-1 are highly
      expressed in neurons of the npEW, but the way these three neuropeptides act
      together in response to acute stress is not known. We hypothesized that Ucn1,
      CART and nesfatin-1 are colocalized in npEW neurons and that these neurons are
      recruited by acute stress. Using quantitative immunocytochemistry and the reverse
      transcriptase polymerase chain reaction (RT-PCR), we support this hypothesis, by
      showing in B6C3F1/Crl mice that Ucn1, CART and nesfatin-1 occur in the same
      neurons of the npEW nucleus. More specifically, Ucn1 and CART revealed a complete
      colocalization in the same perikarya, while 90% of these neurons are also
      nesfatin-1-immunoreactive. Furthermore, acute (restraint) stress stimulates the
      general secretory activity of these npEW neurons (increased presence of Fos) and
      the production of Ucn1, CART and nesfatin-1: Ucn1, CART and nesfatin-1(NUCB2)
      mRNAs have been increased compared to controls by x1.8, x2.0 and x2.6,
      respectively (p<0.01). We conclude that Ucn1, CART and nesfatin-1/NUCB2 are
      specifically involved in the response of npEW neurons to acute stress in the
      mouse.

PMID- 20043891
TI  - Ethanol self-administration modulation of NMDA receptor subunit and related
      synaptic protein mRNA expression in prefrontal cortical fields in cynomolgus
      monkeys.
AB  - BACKGROUND: Functional impairment of the orbital and medial prefrontal cortex
      underlies deficits in executive control that characterize addictive disorders,
      including alcohol addiction. Previous studies indicate that alcohol alters
      glutamate neurotransmission and one substrate of these effects may be through the
      reconfiguration of the subunits constituting ionotropic glutamate receptor
      (iGluR) complexes. Glutamatergic transmission is integral to cortico-cortical and
      cortico-subcortical communication, and alcohol-induced changes in the abundance
      of the receptor subunits and/or their splice variants may result in critical
      functional impairments of prefrontal cortex in the alcohol-addicted state.
      METHODS AND RESULTS: The effects of chronic ethanol self-administration on
      glutamate receptor ionotropic NMDA (GRIN), as well as GRIN1 splice variant mRNA
      expression was studied in the orbitofrontal cortex (OFC; Area 13), dorsolateral
      prefrontal cortex (DLPFC; Area 46) and anterior cingulate cortex (ACC; Area 24)
      of male cynomolgus monkeys. Chronic ethanol self-administration resulted in
      significant changes in the expression of NMDA subunit mRNA expression in the
      DLPFC and OFC, but not the ACC. In DLPFC, the overall expression of NMDA subunits
      was significantly decreased in ethanol treated monkeys. Slight but significant
      changes were observed for synaptic associated protein 102 kD (SAP102) and
      neuronal nitric oxide synthase (nNOS) mRNAs. In OFC, the NMDAR1 variant GRIN1-1
      was reduced while GRIN1-2 was increased. Furthermore, no significant changes in
      GFAP protein levels were observed in either the DLPFC or OFC. CONCLUSION: Results
      from these studies provide the first demonstration of posttranscriptional
      regulation of iGluR subunits in the primate brain following long-term ethanol
      self-administration. Furthermore, changes in these transcripts do not appear to
      reflect changes in glial activation or loss. Further studies examining the
      expression and cellular localization of subunit proteins and receptor
      pharmacology would shed more light on the findings reported here.

PMID- 20043895
TI  - Progressive vestibular mutation leads to elevated anxiety.
AB  - Anxiety disorders are among the most common mental disorders, and are comorbid
      with balance disorders in a significant proportion of these individuals.
      Presently, it is unclear whether anxiety and balance disorders are causally
      related, and what direction this causality may take. We argue that balance
      disorders may predispose an individual to anxiety and that demonstration of such
      causality may be informative to the development of preferred treatment for such
      individuals. To demonstrate that balance disorders may predispose to anxiety, we
      studied headbanger (Hdb) mutant mice in which the balance disorder is due to
      progressive vestibular impairment and wildtype (Wt) mice. Balance was assessed by
      swim and tail-hang tests that demonstrated clear behavioral balance deficits in
      the Hdb mice. Anxiety was assessed by open-field and elevated plus-maze tests,
      which confirmed elevated anxiety in the Hdb mice. These findings demonstrate that
      congenital vestibular genotype predisposes the animal to elevated levels of
      anxiety in space-related tests. Similar causality in clinics may redirect
      treatment strategies in afflicted patients.

PMID- 20043897
TI  - Development of a multiplex ligation-dependent probe amplification (MLPA) assay
      for quantification of the OCRL1 gene.
AB  - OBJECTIVES: To develop and evaluate the efficacy of Multiplex Ligation-dependent
      Probe Amplification (MLPA) technique in detection of genomic rearrangements of
      the OCRL1 gene associated with Oculocerebrorenal syndrome of Lowe (OCRL). DESIGN
      AND METHODS: Four synthetic MLPA probe sets have been designed to measure exons
      copy number in OCRL1 gene. After OCRL1 MLPA probe sets validation in 7 OCRL1
      deleted patients, we screened 5 female patients to asses their carrier status and
      15 patients with suspected OCRL, previously diagnosed as sequence-negative.
      RESULTS: MLPA was able to detect all the known deletions. Two of five females
      were detected as carrier for the family mutation. Neither mosaic deletion nor
      duplication was found in the 15 patients suspected of having Lowe syndrome.
      CONCLUSIONS: Our MLPA allows rapid and precise OCRL1 gene quantification.
      Moreover this study provides no further evidence for the hypothesis that
      duplications and deletion somatic mosaic deletions account for the fraction of
      patients who have no detectible mutation after the usual screening procedures.

PMID- 20043896
TI  - Impaired spine formation and learning in GPCR kinase 2 interacting protein-1
      (GIT1) knockout mice.
AB  - The G-protein coupled receptor (GPCR)-kinase interacting proteins 1 and 2 (GIT1
      and GIT2) are scaffold proteins with ADP-ribosylating factor GTPase activity.
      GIT1 and GIT2 control numerous cellular functions and are highly expressed in
      neurons, endothelial cells and vascular smooth muscle cells. GIT1 promotes
      dendritic spine formation, growth and motility in cultured neurons, but its role
      in brain in vivo is unknown. By using global GIT1 knockout mice (GIT1 KO), we
      show that compared to WT controls, deletion of GIT1 results in markedly reduced
      dendritic length and spine density in the hippocampus by 36.7% (p<0.0106) and
      35.1% (p<0.0028), respectively. This correlated with their poor adaptation to new
      environments as shown by impaired performance on tasks dependent on learning. We
      also studied the effect of GIT1 gene deletion on brain microcirculation. In
      contrast to findings in systemic circulation, GIT1 KO mice had an intact blood
      brain barrier and normal regional cerebral blood flow as determined with
      radiotracers. Thus, our data suggest that GIT1 plays an important role in brain
      in vivo by regulating spine density involved in synaptic plasticity that is
      required for processes involved in learning.

PMID- 20043898
TI  - Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the
      neurogenic and non-neurogenic domains in the chick otic placode.
AB  - The development of neural tissue starts with the activation of early neural genes
      such as the SoxB1 transcription factors, which are expressed in response to
      signaling molecules. Neural progenitors in the inner ear are only generated in
      the anterior placodal domain, but the mechanisms that determine when and how otic
      neural fate is acquired are still unknown. Here, we show that Sox3 expression
      becomes restricted to the anterior territory of the chick otic field and that
      misexpression of Sox3 induces Sox2 and Delta1 in the non-neurogenic otic
      territory. This suggests that Sox3 plays a central role in the establishment of
      an otic neural fate. Furthermore, Sox3 down-regulates the expression of Lmx1b, a
      marker of the posterior non-neurogenic otic epithelium. The expression of Sox3 is
      maintained by the positive action of FGF8 derived from the otic ectoderm. On the
      contrary, BMP signaling does not have a major influence on neural commitment but
      instead regulates Lmx1b expression in the otic placode. Together, the data
      support the notion that Sox3 is critical for the development of the neural
      elements of the inner ear, and they highlight the importance of localized
      signaling from the ectoderm in establishing the neurogenic vs. non-neurogenic
      anteroposterior asymmetry that characterizes the early otic placode.

PMID- 20043900
TI  - Analysis of Cyp26b1/Rarg compound-null mice reveals two genetically separable
      effects of retinoic acid on limb outgrowth.
AB  - The role of retinoic acid (RA) in limb development is unclear, although it has
      been suggested to be a proximalizing factor which plays a morphogenetic role in
      pattern formation. Exogenous RA produces a teratogenic effect on limb morphology;
      similarly, changes in the endogenous distribution of RA following genetic
      ablation of the RA-metabolizing enzyme, CYP26B1, result in phocomelia accompanied
      by changes in expression of proximo-distal (P-D) patterning genes, increased cell
      death, and delayed chondrocyte maturation. Here we show that disruption of RA
      receptor (RAR) gamma in a Cyp26b1(-/-) background is able to partially rescue
      limb skeletal morphology without restoring normal expression of proximo-distal
      patterning genes. We further show that embryos deficient in CYP26B1 exhibit early
      localized domains of mesenchymal cell death, which are reduced in compound-null
      animals. This model reveals two genetically separable effects of RA in the limb:
      an apoptotic effect mediated by RARgamma in the presence of ectopic RA, and a P-D
      patterning defect which is uncovered following the loss of both CYP26B1 and
      RARgamma. These data provide genetic evidence to clarify the roles of both RA and
      CYP26B1 in limb outgrowth and proximo-distal patterning.

PMID- 20043899
TI  - Evidence for an early role for BMP4 signaling in thymus and parathyroid
      morphogenesis.
AB  - The thymus and parathyroids are pharyngeal endoderm-derived organs that develop
      from common organ primordia, which undergo a series of morphological events
      resulting in separate organs in distinct locations in the embryo. Previous gene
      expression and functional analyses have suggested a role for BMP4 signaling in
      early thymus organogenesis. We have used conditional deletion of Bmp4 or Alk3
      from the pharyngeal endoderm and/or the surrounding mesenchyme using Foxg1-Cre,
      Wnt1-Cre or Foxn1-Cre. Deleting Bmp4 from both neural crest cells (NCC) and early
      endoderm-derived epithelial cells in Foxg1-Cre;Bmp4 conditional mutants resulted
      in defects in thymus-parathyroid morphogenesis. Defects included reduced
      condensation of mesenchymal cells around the epithelium, partial absence of the
      thymic capsule, a delay in thymus and parathyroid separation, and failed or
      dramatically reduced organ migration. Patterning of the primordia and initial
      organ differentiation were not affected in any of the mutants. Deleting Bmp4 from
      NCC-derived mesenchyme or differentiating thymic epithelial cells (TECs) had no
      effects on thymus-parathyroid development, while loss of Alk3 from either neural
      crest cells or TECs resulted in only a mild thymic hypoplasia. these results show
      that the processes of cell specification and morphogenesis during thymus
      parathyroid development are independently controlled, and suggest a specific
      temporal and spatial role for BMP4-mediated epithelial-mesenchymal interactions
      during early thymus and parathyroid morphogenesis.

PMID- 20043901
TI  - Pivotal role of hmx2 and hmx3 in zebrafish inner ear and lateral line
      development.
AB  - hmx2 (nkx5.2) and hmx3 (nkx5.1) are highly conserved homeobox transcription
      factors required for mouse inner ear development. We have identified four hmx
      genes that are expressed in developing mechanosensory organs in zebrafish.
      Knockdown of both hmx2 and hmx3 disrupts formation of the mechanosensory
      neuromasts and also leads to impaired vestibular function in which utricular
      maculae fail to develop and the utricular otolith gradually fuses with the
      saccular otolith. We demonstrate that pax5, known to be required for development
      of the utricular maculae, is expressed downstream of hmx2 and hmx3. In addition,
      we show that FGF signaling regulates expression of hmx2 and hmx3 in the otic
      vesicle, and conversely, hmx2 and hmx3 maintain the expression of fgf ligands,
      thus revealing a novel tissue-specific feedback mechanism. Our data suggest that
      hmx2 and hmx3 act as cell autonomous factors required redundantly for cell fate
      specification and differentiation during inner ear and lateral line development.

PMID- 20043902
TI  - Cdx2 regulates patterning of the intestinal epithelium.
AB  - Cdx1, Cdx2 and Cdx4 encode homeodomain transcription factors that are involved in
      vertebral anterior-posterior (AP) patterning. Cdx1 and Cdx2 are also expressed in
      the intestinal epithelium during development, suggesting a role in this tissue.
      Intestinal defects have not been reported in Cdx1 null mutants, while Cdx2 null
      mutants die at embryonic day 3.5 (E3.5), thus precluding assessment of the null
      phenotype at later stages. To circumvent this latter shortcoming, we have used a
      conditional Cre-lox strategy to inactivate Cdx2 in the intestinal epithelium.
      Using this approach, we found that ablation of Cdx2 at E13.5 led to a
      transformation of the small intestine to a pyloric stomach-like identity,
      although the molecular nature of the underlying mesenchyme remained unchanged.
      Further analysis of Cdx1-Cdx2 double mutants suggests that Cdx1 does not play a
      critical role in the development of the small intestine, at least after E13.5.

PMID- 20043903
TI  - Locally available heparin modulates inflammatory cell recruitment in a manner
      independent of anticoagulant activity.
AB  - Heparin is known to possess anti-inflammatory properties that in many cases
      appear to be separable from its anticoagulant activity. Mast cells, located in
      tissue, are the sole source of endogenous heparin, which may be involved in
      control of the inflammatory response. The majority of studies of the effects of
      heparin on the inflammatory response, carried out to date, have involved systemic
      administration and the potential influence of heparin in the site of inflammation
      has been less clear. In the present study, the effects of locally administered
      heparin and a non-anticoagulant derivative were investigated on leucocyte
      accumulation in the inflamed peritoneal cavity and leucocyte-endothelial
      interactions in the mesenteric microcirculation of the rat. Heparin and non
      anticoagulant heparin inhibited the influx of neutrophils to the site of
      inflammation, as well as leucocyte rolling and adhesion in post-capillary
      venules. These effects were apparent only while heparin was present in the
      peritoneal cavity and plasma and may reflect, in part, an action on resident
      peritoneal cells, as the heparins tested were found also to inhibit the
      expression of endothelial adhesion molecules in response to products of activated
      mononuclear cells, in vitro. Our data show that locally administered heparin has
      anti-inflammatory effects in an in vivo model of peritoneal inflammation whilst
      present at the site of inflammation. These non-anticoagulant properties may
      involve interaction with cells in the site of inflammation, in addition to
      inhibiting cell adhesion at the level of the microcirculation.

PMID- 20043904
TI  - Identification of a fibronectin interaction site in the extracellular matrix
      protein ameloblastin.
AB  - Mammalian teeth are composed of hydroxyapatite crystals that are embedded in a
      rich extracellular matrix. This matrix is produced by only two cell types, the
      mesenchymal odontoblasts and the ectodermal ameloblasts. Ameloblasts secrete the
      enamel proteins amelogenin, ameloblastin, enamelin and amelotin. Odontoblasts
      secrete collagen type I and several calcium-binding phosphoproteins including
      dentin sialophosphoprotein, dentin matrix protein, bone sialoprotein and
      osteopontin. The latter four proteins have recently been grouped in the family of
      the SIBLINGs (small integrin-binding ligand, N-linked glycoproteins) because they
      display similar gene structures and because they contain an RGD tripeptide
      sequence that binds to integrin receptors and thus mediates cell adhesion. We
      have prepared all the other tooth-specific proteins in recombinant form and
      examined whether they might also promote cell adhesion similar to the SIBLINGs.
      We found that only ameloblastin consistently mediated adhesion of osteoblastic
      and fibroblastic cells to plastic or titanium surfaces. The activity was
      dependent on the intact three-dimensional structure of ameloblastin and required
      de novo protein synthesis of the adhering cells. By deletion analysis and in
      vitro mutagenesis, the active site could be narrowed down to a sequence of 13
      amino acid residues (VPIMDFADPQFPT) derived from exon 7 of the rat ameloblastin
      gene or exons 7-9 of the human gene. Kinetic studies and RNA interference
      experiments further demonstrated that this sequence does not directly bind to a
      cell surface receptor but that it interacts with cellular fibronectin, which in
      turn binds to integrin receptors. The identification of a fibronectin-binding
      domain in ameloblastin might permit interesting applications for dental
      implantology. Implants could be coated with peptides containing the active
      sequence, which in turn would recruit fibronectin from the patient's blood. The
      recruited fibronectin should then promote cell adhesion on the implant surface,
      thereby accelerating osseointegration of the implant.

PMID- 20043905
TI  - S-phase and DNA damage activated establishment of sister chromatid cohesion-
      importance for DNA repair.
AB  - By holding sister chromatids together from the moment of their formation until
      their separation at anaphase, the multi subunit protein complex Cohesin
      guarantees correct chromosome segregation. This S-phase established chromatid
      cohesion is also essential for repair of DNA double strand breaks (DSB) in
      postreplicative cells. In addition, Cohesin has to be recruited to a DSB, and new
      cohesion has to form in response to the damage for repair. When it became clear
      that cohesion is created de novo in response to DNA breaks, the term "damage
      induced cohesion" (DI-cohesion) was coined. It is now established that certain
      factors are needed for establishment of both S-phase and DI-cohesion, while
      others have been found to be unique for respective process. In addition, post
      translational modifications of Cohesin components that are functionally important
      for cohesion formation, either during S-phase or in response to damage, have
      recently been identified. Here, we present and discuss the current models for
      establishment of S-phase and DI-cohesion in the context of their involvement in
      DSB repair.

PMID- 20043906
TI  - In vivo assessment of brain monoamine systems in parkin gene carriers: a PET
      study.
AB  - PET studies in parkin-linked parkinsonism have generally been performed to assess
      striatal dopaminergic dysfunction and very little is known about the involvement
      of other monoaminergic structures in these patients. Measurements of (18)F-dopa
      uptake into serotonergic and noradrenergic structures provide an indication of
      the functional integrity of these nerve terminals. We used (18)F-dopa PET to
      assess changes in brain monoaminergic function associated with parkin mutations.
      Twelve patients with parkin-linked parkinsonism and 12 asymptomatic parkin
      heterozygotes were included in the study. Eleven healthy controls, 12 patients
      with idiopathic Parkinson's disease (IPD), and four patients with PINK1 mutations
      were also investigated for comparison. parkin patients and IPD patients were
      matched for striatal dopaminergic dysfunction, as measured by (18)F-dopa uptake.
      Compared to controls, parkin patients showed significant (18)F-dopa reductions in
      the caudate, putamen, ventral striatum, locus coeruleus, midbrain raphe, and
      pallidum. The same structures showed reduced uptake in IPD patients, who
      additionally had significant reductions in hypothalamus, ventral anterior
      thalamus, and pineal gland. Direct comparison of parkin with IPD patients showed
      that hypothalamus was targeted in IPD and midbrain raphe in parkin disease.
      Patients with PINK1 mutation and several parkin heterozygotes also showed
      monoaminergic dysfunction. These findings suggest that parkin patients and IPD
      patients with similar striatal dysfunction have different patterns of
      monoaminergic involvement, with more widespread dysfunction in IPD.

PMID- 20043907
TI  - Abeta(25-35) as proxyholder for amyloidogenic peptides: in vivo evidence.

PMID- 20043909
TI  - Transbilayer (flip-flop) lipid motion and lipid scrambling in membranes.
AB  - This paper reviews the current knowledge on the various mechanisms for
      transbilayer, or flip-flop, lipid motion in model and cell membranes, enzyme
      assisted lipid transfer by flippases, floppases and scramblases is briefly
      discussed, while non-catalyzed lipid flip-flop is reviewed in more detail.
      Transbilayer lipid motion may occur as a result of the insertion of foreign
      molecules (detergents, lipids, or even proteins) in one of the membrane leaflets.
      It may also be the result of the enzymatic generation of lipids, e.g.
      diacylglycerol or ceramide, at one side of the membrane. Transbilayer motion
      rates decrease in the order diacylglycerol>>ceramide>>phospholipids. Ceramide,
      but not diacylglycerol, can induce transbilayer motion of other lipids, and
      bilayer scrambling. Transbilayer lipid diffusion and bilayer scrambling are
      defined as two conceptually and mechanistically different processes. The
      mechanism of scrambling appears to be related to local instabilities caused by
      the non-lamellar ceramide molecule, or by other molecules that exhibit a
      relatively slow flip-flop rate, when asymmetrically inserted or generated in one
      of the monolayers in a cell or model membrane.

PMID- 20043908
TI  - Cough following low thoracic hemisection in the cat.
AB  - A function of the abdominal expiratory muscles is the generation of cough, a
      critical respiratory defense mechanism that is often disrupted following spinal
      cord injury. We assessed the effects of a lateral T9/10 hemisection on cough
      production at 4, 13 and 21 weeks post-injury in cats receiving extensive
      locomotor training. The magnitudes of esophageal pressure as well as of bilateral
      rectus abdominis electromyogram activity during cough were not significantly
      different from pre-injury values at all time points evaluated. The results show
      that despite considerable interruption of the descending pre-motor drive from the
      brainstem to the expiratory motoneuron pools, the cough motor system shows a
      significant function by 4 weeks following incomplete thoracic injury.

PMID- 20043910
TI  - RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling
      components of the IkappaB kinase complex.
AB  - RKIP was first identified as an inhibitor of the Raf-MEK-ERK signaling pathway.
      RKIP was also found to play an important role in the NF-kappaB pathway. Genetic
      and biochemical studies demonstrated that RKIP functioned as a scaffold protein
      facilitating the phosphorylation of IkappaB by upstream kinases. However,
      contrary to what one would expect of a scaffold protein, our results show that
      RKIP has an overall inhibitory effect on the NF-kappaB transcriptional
      activities. Since NF-kappaB target gene expression is subject to negative
      regulation involving the optimal induction of negative regulators, our data
      support a hypothesis that RKIP inhibits NF-kappaB activity via the auto
      regulatory feedback loop by rapidly inducing the expression and synthesis of
      inhibitors of NF-kappaB activation.

PMID- 20043911
TI  - The glucagon receptor antagonist BI-32169 constitutes a new class of lasso
      peptides.
AB  - The glucagon receptor antagonist BI-32169, recently isolated from Streptomyces
      sp., was described as a bicyclic peptide, although its primary structure
      comprises conserved elements of class I and class II lasso peptides. Tandem mass
      spectrometric and nuclear magnetic resonance spectroscopic studies revealed that
      BI-32169 is a lasso-structured peptide constituting the new class III of lasso
      peptides. The determined lasso fold opens new avenues to improve the promising
      biological activity of BI-32169.

PMID- 20043912
TI  - Structural and functional evidence for a substrate exclusion mechanism in
      mammalian tolloid like-1 (TLL-1) proteinase.
AB  - Bone morphogenetic protein-1 (BMP-1)/tolloid proteinases are fundamental to
      regulating dorsal ventral patterning and extracellular matrix deposition. In
      mammals there are four proteinases, the splice variants BMP-1 and mammalian
      tolloid (mTLD), and tolloid like-1 and -2 (TLL-1/2). BMP-1 has the highest
      catalytic activity and lacks three non-catalytic domains. We demonstrate that TLL
      1, which has intermediate activity, forms a calcium-ion dependent dimer with
      monomers stacked side-by-side. In contrast, truncated TLL-1 molecules having the
      same shorter structure as BMP-1 are monomers and have improved activity towards
      their substrate chordin. The increased activity exceeds not only that of full
      length TLL-1 but also BMP-1.

PMID- 20043914
TI  - Cloning and characterization of a Gasp homolog from the spruce budworm,
      Choristoneura fumiferana, and its putative role in cuticle formation.
AB  - Proteins that are capable of binding chitin play essential roles in the synthesis
      and structural integrity of the insect cuticle and peritrophic matrix. In the
      course of developing expressed sequence tag (EST) libraries for the eastern
      spruce budworm, Choristoneura fumiferana, we identified an abundant cDNA encoding
      a homolog of the Drosophila "gasp" gene (Gene Analogous to Small Peritrophins).
      For the present work, we undertook the characterization of this new homolog,
      CfGasp, in an effort to identify its role during larval development. As shown for
      DmGasp, the C. fumiferana homolog was found to contain three type-2 chitin
      binding domains (CBDs), which were also found in Gasp orthologs retrieved from
      GenBank. In a phylogenetic analysis, these Gasp proteins formed a tight cluster,
      distinct from the midgut-specific peritrophins with which they share the cysteine
      containing CBDs so far considered absent from cuticular proteins. However, unlike
      what has been shown for peritrophins, CfGasp transcript levels were low in larval
      midguts and most abundant in epidermis, while they were low in trachea and
      ovaries. Transcript levels increased during larval molts in a pattern similar to
      that observed for exocuticular proteins in other insects. In addition, the
      recombinant protein was shown to be capable of binding chitin. Altogether, these
      results suggest a structural role for CfGasp in exocuticle formation.

PMID- 20043913
TI  - A novel class of bacterial translation factor RF3 mutations suggests specific
      structural domains for premature peptidyl-tRNA drop-off.
AB  - The bacterial translation factor RF3 promotes translation termination by
      recycling the tRNA-mimicking release factors, RF1 and RF2, after mature
      polypeptide release. RF3 also enhances the premature peptidyl-tRNA drop-off
      reaction in the presence of RRF and EF-G. Despite the recently resolved X-ray
      crystal structure of RF3, the molecular details of the bimodal functionality of
      RF3 remain obscure. In this report, we demonstrate a novel class of RF3 mutations
      specifically defective in the tRNA drop-off reaction. These mutations suggest
      differential molecular pathways closely related to the guanine nucleotide modes
      of RF3.

PMID- 20043915
TI  - Expression of HSP60 and HSP70 in white shrimp, Litopenaeus vannamei in response
      to bacterial challenge.
AB  - In the present study, cDNA encoding a heat shock protein 60 (LvHSP60) gene in
      Litopenaeus vannamei was cloned using a combination of homology and rapid
      amplification of cDNA end (RACE) methods. The full length of the LvHSP60 cDNA was
      found to be 2379bp, with a 1737bp open reading frame. The translated amino acid
      sequence consisted of 579 residues with a calculated molecular mass of 60.8kD and
      an isoelectronic point (pI) of 5.97. Comparison of the deduced amino acid
      sequence showed that it has high identity (85-89%) with HSP60/chaperonins from
      insects and mammals. Quantitative real-time PCR and Western blot analysis were
      carried out to investigate the expression patterns and distribution profiles of
      LvHSP60 before and after stimulation with the Gram-positive bacterium
      Staphylococcus aureus and the Gram-negative bacterium Vibrio alginolyticus.
      LvHSP60 mRNA was found to be both constitutive and inducible, and was highly
      expressed in haemocytes and almost all tissues examined, including muscle,
      stomach, heart, hepatopancreas and gill tissue, but it was less strongly
      expressed in the intestine. The expression analysis revealed that LvHSP60 was
      significantly up-regulated in the gills, hepatopancreas and haemocytes after
      bacterial challenge. Transcription of LvHSP70 was also induced in haemocytes and
      the hepatopancreas after different bacteria injection. Subsequent flow cytometry
      analysis showed that the concentration of Ca(2+) ions increased significantly
      within bacteria-challenged haemocytes by 1.5h after injection. The results
      indicate that LvHSP60 and LvHSP70 may play important roles in mediating the
      immune responses of L. vannamei to bacterial challenge, and that the Ca(2+)
      signalling transduction pathway may be involved in the initiation of the shrimp's
      immune responses in early stages of infection.

PMID- 20043917
TI  - Energetic frustration of apomyoglobin folding: role of the B helix.
AB  - Apomyoglobin folds by a sequential mechanism in which the A, G, and H helix
      regions undergo rapid collapse to form a compact intermediate onto which the
      central portion of the B helix subsequently docks. To investigate the factors
      that frustrate folding, we have made mutations in the N-terminus of the B helix
      to stabilize helical structure (in the mutant G23A/G25A) and to promote native
      like hydrophobic packing interactions with helix G (in the mutant H24L/H119F).
      The kinetic and equilibrium intermediates of G23A/G25A and H24L/H119F were
      studied by hydrogen exchange pulse labeling and interrupted hydrogen/deuterium
      exchange combined with NMR. For both mutants, stabilization of helical structure
      in the N-terminal region of the B helix is confirmed by increased exchange
      protection in the equilibrium molten globule states near pH 4. Increased
      protection is also observed in the GH turn region in the G23A/G25A mutant,
      suggesting that stabilization of the B helix facilitates native-like interactions
      with the C-terminal region of helix G. These interactions are further enhanced in
      H24L/H119F. The kinetic burst phase intermediates of both mutants show increased
      protection, relative to wild-type protein, of amides in the N-terminus of the B
      helix and in part of the E helix. Stabilization of the E helix in the
      intermediate is attributed to direct interactions between E helix residues and
      the newly stabilized N-terminus of helix B. Stabilization of native packing
      between the B and G helices in H24L/H119F also favors formation of native-like
      interactions in the GH turn and between the G and H helices in the ensemble of
      burst phase intermediates. We conclude that instability at the N-terminus of the
      B helix of apomyoglobin contributes to the energetic frustration of folding by
      preventing docking and stabilization of the E helix.

PMID- 20043916
TI  - Helix dynamics in LacY: helices II and IV.
AB  - Biochemical and biophysical studies based upon crystal structures of both a
      mutant and wild-type lactose permease from Escherichia coli (LacY) in an inward
      facing conformation have led to a model for the symport mechanism in which both
      sugar and H+ binding sites are alternatively accessible to both sides of the
      membrane. Previous findings indicate that the face of helix II with Asp68 is
      important for the conformational changes that occur during turnover. As shown
      here, replacement of Asp68 at the cytoplasmic end of helix II, particularly with
      Glu, abolishes active transport but the mutants retain the ability to bind
      galactopyranoside. In the x-ray structure, Asp68 and Lys131 (helix IV) lie within
      approximately 4.2 A of each other. Although a double mutant with Cys replacements
      at both position 68 and position 131 cross-links efficiently, single replacements
      for Lys131 exhibit very significant transport activity. Site-directed alkylation
      studies show that sugar binding by the Asp68 mutants causes closure of the
      cytoplasmic cavity, similar to wild-type LacY; however, strikingly, the
      probability of opening the periplasmic pathway upon sugar binding is markedly
      reduced. Taken together with results from previous mutagenesis and cross-linking
      studies, these findings lead to a model in which replacement of Asp68 blocks a
      conformational transition involving helices II and IV that is important for
      opening the periplasmic cavity. Evidence suggesting that movements of helices II
      and IV are coupled functionally with movements in the pseudo-symmetrically paired
      helices VIII and X is also presented.

PMID- 20043918
TI  - Substitution of Glu122 by glutamine revealed the function of the second water
      molecule as a proton donor in the binuclear metal enzyme creatininase.
AB  - Creatininase is a binuclear zinc enzyme and catalyzes the reversible conversion
      of creatinine to creatine. It exhibits an open-closed conformational change upon
      substrate binding, and the differences in the conformations of Tyr121, Trp154,
      and the loop region containing Trp174 were evident in the enzyme-creatine complex
      when compared to those in the ligand-free enzyme. We have determined the crystal
      structure of the enzyme complexed with a 1-methylguanidine. All subunits in the
      complex existed as the closed form, and the binding mode of creatinine was
      estimated. Site-directed mutagenesis revealed that the hydrophobic residues that
      show conformational change upon substrate binding are important for the enzyme
      activity. We propose a catalytic mechanism of creatininase in which two water
      molecules have significant roles. The first molecule is a hydroxide ion (Wat1)
      that is bound as a bridge between the two metal ions and attacks the carbonyl
      carbon of the substrate. The second molecule is a water molecule (Wat2) that is
      bound to the carboxyl group of Glu122 and functions as a proton donor in
      catalysis. The activity of the E122Q mutant was very low and it was only
      partially restored by the addition of ZnCl(2) or MnCl(2). In the E122Q mutant,
      k(cat) is drastically decreased, indicating that Glu122 is important for
      catalysis. X-ray crystallographic study and the atomic absorption spectrometry
      analysis of the E122Q mutant-substrate complex revealed that the drastic decrease
      of the activity of the E122Q was caused by not only the loss of one Zn ion at the
      Metal1 site but also a critical function of Glu122, which most likely exists for
      a proton transfer step through Wat2.

PMID- 20043919
TI  - The humanness of macaque antibody sequences.
AB  - Chimeric, humanized and human antibodies have successively been exploited as
      therapeutics because their increasing human ('self') character is expected to
      correspond with decreased immunogenicity, which is critical for their clinical
      development. Thus, humanness has been inferred to predict antibody
      immunogenicity. Humanness of antibody variable regions (V-regions) has recently
      been studied using a parameter (here referred to as the H-score) that evaluates
      similarity to expressed human sequences. Macaque (Macaca fascicularis) antibody
      sequences are of particular interest because they have been suggested to have
      extremely human-like character and, recently, macaque single-chain variable
      fragments with very high affinity for various antigens have been isolated. In
      this study, the H-scores of all macaque antibody V-regions available in sequence
      data banks were compared with those of their human counterparts using statistical
      tests. The results were found to be influenced by the relative size of the human
      families to which the macaque V-regions are related. As the relevance of families
      to immunogenicity is suspected but unproven, a new parameter (the 'G-score') was
      derived from the H-score to avoid this influence, and macaque V-region sequences
      were reanalyzed using the G-score. Both parameters show that these regions cannot
      be regarded as human when they derive from heavy chains, but the humanness of
      light chains is variable. It was shown that 'germline humanization' of a macaque
      V-region favourably influenced its humanness, as evaluated by both H-score and G
      score. In addition, the humanness of macaque sequences presented in patents has
      been analyzed. The H-score and G-score define objectively the humanness of
      antibody V-regions, and their use is exemplified here.

PMID- 20043920
TI  - Slowing bacterial translation speed enhances eukaryotic protein folding
      efficiency.
AB  - The mechanisms for de novo protein folding differ significantly between bacteria
      and eukaryotes, as evidenced by the often observed poor yields of native
      eukaryotic proteins upon recombinant production in bacterial systems. Polypeptide
      synthesis rates are faster in bacteria than in eukaryotes, but the effects of
      general variations in translation rates on protein folding efficiency have
      remained largely unexplored. By employing Escherichia coli cells with mutant
      ribosomes whose translation speed can be modulated, we show here that reducing
      polypeptide elongation rates leads to enhanced folding of diverse proteins of
      eukaryotic origin. These results suggest that in eukaryotes, protein folding
      necessitates slow translation rates. In contrast, folding in bacteria appears to
      be uncoupled from protein synthesis, explaining our findings that a generalized
      reduction in translation speed does not adversely impact the folding of the
      endogenous bacterial proteome. Utilization of this strategy has allowed the
      production of a native eukaryotic multidomain protein that has been previously
      unattainable in bacterial systems and may constitute a general alternative to the
      production of aggregation-prone recombinant proteins.

PMID- 20043921
TI  - Mathematical study of feedback control roles and relevance in stress
      erythropoiesis.
AB  - This work is devoted to mathematical modelling of erythropoiesis. We propose a
      new multi-scale model, in which we bring together erythroid progenitor dynamics
      and intracellular regulatory network that determines erythroid cell fate. All
      erythroid progenitors are divided into several sub-populations according to their
      maturity. Two intracellular proteins, Erk and Fas, are supposed to be determinant
      for regulation of self-renewal, differentiation and apoptosis. We consider two
      growth factors, erythropoietin and glucocorticoids, and describe their dynamics.
      Several feedback controls are introduced in the model. We carry out computer
      simulations of anaemia and compare the obtained results with available
      experimental data on induced anaemia in mice. The main objective of this work is
      to evaluate the roles of the feedback controls in order to provide more insights
      into the regulation of erythropoiesis. Feedback by Epo on apoptosis is shown to
      be determinant in the early stages of the response to anaemia, whereas regulation
      through intracellular regulatory network, based on Erk and Fas, appears to
      operate on a long-term scale.

PMID- 20043922
TI  - Rate-variation need not defeat phylogenetic inference through pairwise sequence
      comparisons.

PMID- 20043923
TI  - Alternative splicing regulatory network reconstruction from exon array data.
AB  - Pre-mRNA alternative splicing (AS) allows individual genes to produce multiple
      types of mRNA and associated protein isoforms. While AS regulation enables the
      production of the hundreds of thousands of types of proteins needed for the
      normal functioning of the human cell, it also presents many opportunities for the
      onset of cancer and other diseases. The AS process is known to be regulated by a
      group of serine/arginine rich (SR) proteins, heterogeneous nuclear
      ribonucleoproteins (hnRNPs), and small nuclear ribonucleoprotein (snRNP)
      particles through a complex assembly. Each gene-exon is regulated by one or
      multiple splicing regulators, from which one may hypothesize the existence of an
      alternative splicing regulatory network (SRN). The SRN contains a list of gene
      exons, for each of which the factors that up/down regulate them are provided.
      Since defects in the SRN play key roles in human disease, a reconstruction of
      human SRN could be used to facilitate the design of diagnostic and therapeutic
      strategies. In this paper, we present a methodology to automate genome-wide SRN
      reconstruction. We construct SRN based on an extensive correlation analysis of
      human exon expression microarray data, conventional gene expression microarray
      profiles, and an experimentally verified AS and transcriptional regulatory
      interaction training set. This SRN reconstruction methodology is demonstrated and
      software (AutoNet) that automates the reconstruction of SRN is developed. A
      genome-wide SRN was constructed for normal human cells and an assessment of the
      reliability of each predicted interaction is provided. Human SRN we constructed
      are free available from our web portal:
      https://ruby.chem.indiana.edu/scorenfl/srn_results/lookup0.php.

PMID- 20043924
TI  - A mechanomolecular model for the movement of chromosomes during mitosis driven by
      a minimal kinetochore bicyclic cascade.
AB  - During mitosis chromosomes use a complex network of dynamic microtubules to find
      the cell equator in preparation for division signals. The roles of cellular
      chemical signals in mechanisms driving mitotic chromosomal movements are not well
      understood. In this paper we propose a mathematical model of this process which
      incorporates a molecular scale model of kinetochore-microtubule interactions into
      a negative feedback loop between spindle forces and local kinetochore biochemical
      reactions. This system allows kinetochore biochemical reactions to control and
      coordinate chromosome movement thus providing a direct connection between
      mechanical signals and mitosis chemical species. Our feedback control model can
      recreate chromosome movement from prometaphase to anaphase in good agreement with
      experimental data.

PMID- 20043925
TI  - Mathematical modeling of thrombus growth in mesenteric vessels.
AB  - Richardson's phenomenological mathematical model of the thrombi growth in
      microvessels is extended to describe the realistic features of the phenomenon.
      The main directions of the generalization of Richardson's model are: (1) the
      dependence of platelet activation time on the distance from the injured vessel
      wall; (2) the non-homogeneity of the platelet distribution in blood flow in the
      vicinity of the vessel wall; (3) the adequate choice of the phenomenological
      function describing the dependence of blood velocity on the thrombus size. The
      generalization of the model corresponds to the main experimental results and
      theoretical considerations concerning thrombus formation obtained in recent
      years. The extended model permits to achieve qualitative agreement between model
      and experimental data.

PMID- 20043926
TI  - Cost-effective control of chronic viral diseases: finding the optimal level of
      screening and contact tracing.
AB  - Chronic viral diseases such as human immunodeficiency virus (HIV) and hepatitis B
      virus (HBV) afflict millions of people worldwide. A key public health challenge
      in managing such diseases is identifying infected, asymptomatic individuals so
      that they can receive antiviral treatment. Such treatment can benefit both the
      treated individual (by improving quality and length of life) and the population
      as a whole (through reduced transmission). We develop a compartmental model of a
      chronic, treatable infectious disease and use it to evaluate the cost and
      effectiveness of different levels of screening and contact tracing. We show that:
      (1) the optimal strategy is to get infected individuals into treatment at the
      maximal rate until the incremental health benefits balance the incremental cost
      of controlling the disease; (2) as one reduces the disease prevalence by moving
      people into treatment (which decreases the chance that they will infect others),
      one should increase the level of contact tracing to compensate for the decreased
      effectiveness of screening; (3) as the disease becomes less prevalent, it is
      optimal to spend more per case identified; and (4) the relative mix of screening
      and contact tracing at any level of disease prevalence is such that the marginal
      efficiency of contact tracing (cost per infected person found) equals that of
      screening if possible (e.g., when capacity limitations are not binding). We also
      show how to determine the cost-effective equilibrium level of disease prevalence
      (among untreated individuals), and we develop an approximation of the path of the
      optimal prevalence over time. Using this, one can obtain a close approximation of
      the optimal solution without having to solve an optimal control problem. We apply
      our methods to an example of hepatitis B virus.

PMID- 20043927
TI  - Variability order of the latent and the infectious periods in a deterministic
      SEIR epidemic model and evaluation of control effectiveness.
AB  - We use distribution theory and ordering of non-negative random variables to study
      the Susceptible-Exposed-Infectious-Removed (SEIR) model with two control
      measures, quarantine and isolation, to reduce the spread of an infectious
      disease. We identify that the probability distributions of the latent period and
      the infectious period are primary features of the SEIR model to formulate the
      epidemic threshold and to evaluate the effectiveness of the intervention
      measures. If the primary features are changed, the conclusions will be altered in
      an importantly different way. For the latent and infectious periods with known
      mean values, it is the dilation, a generalization of variance, of their
      distributions that ranks the effectiveness of these control measures. We further
      propose ways to set quarantine and isolation targets to reduce the controlled
      reproduction number below the threshold using observed initial growth rate from
      outbreak data. If both quarantine and isolation are 100% effective, one can
      directly use the observed growth rate for setting control targets. If they are
      not 100% effective, some further knowledge of the distributions is required.

PMID- 20043928
TI  - A multigroup model for a heterosexually transmitted disease.
AB  - A multigroup model is considered for a disease transmitted heterosexually in
      which there is a core group that has higher sexual activity than other groups. In
      order to develop control strategies to eradicate the disease, type reproduction
      numbers are determined. A graph-theoretic interpretation of type reproduction
      numbers for a star network with a core group at the center is established. Using
      these general formulas for the star network, a two-group model consisting of a
      core and a non-core group is considered. If disease can persist in the core group
      in isolation, then the amount of increase of treatment or decrease of the contact
      rate of infectious males (or females) in the core group that is required to
      eradicate the disease is expressed in terms of model parameters. If disease can
      persist but not in either group in isolation, then the amount of reduction of the
      connection between the two groups needed to eradicate the disease is determined.
      These two cases are illustrated with parameters applicable to gonorrhea in the
      US.

PMID- 20043929
TI  - Application of a two-phenotype color-shift model with heterogeneous growth to a
      rat hepatocarcinogenesis experiment.
AB  - The color-shift model (CSM) was introduced by Kopp-Schneider et al. [1] to
      describe formation and progression of foci of altered hepatocytes (FAH). It
      incorporates the field-effect hypothesis which postulates that entire colonies of
      altered hepatocytes simultaneously alter their phenotype. In the original CSM,
      FAH grow with deterministic growth rate and change their phenotype after an
      exponentially distributed waiting time. A modification of the original color
      shift model (CSM beta) is presented here in which the growth rate varies from
      focus to focus according to a beta distribution. The concept of an exponentially
      distributed waiting time to phenotype change is modified to the concept of a
      random radius at which phenotype changes and this radius is modelled as beta
      distributed. The original and the modified CSM are applied to data from an
      initiation-promotion rat hepatocarcinogenesis experiment with
      diethylnitrosomorpholine (DEN) and N-nitrosomorpholine (NNM), in which two
      phenotypes of FAH were observed in hematoxilin/eosin (H&E) stained liver
      sections. The Cramer-von-Mises Distance is used as a measure for the discrepancy
      between empirical and theoretical size distributions. Comparisons of model fit
      show that considerable improvement is obtained for CSM beta compared to the
      original CSM.

PMID- 20043930
TI  - Endothelial progenitor cells--an evolving story.
AB  - The first description of endothelial progenitor cells (EPC) in 1997 led rapidly
      to substantial changes in our understanding of angiogenesis, and within 5 years
      to the first clinical studies in humans using bone marrow derived EPC to enhance
      coronary neovascularisation and cardiac function after myocardial ischemia.
      However, to improve the success of this therapy a clearer understanding of the
      biology of EPC is needed. This article summarises recent data indicating that
      most EPC are not, in fact, endothelial progenitors but can be better described as
      angiogenic monocytes, and explores the implications this has for their future
      therapeutic use.

PMID- 20043931
TI  - Alpha1-adrenoceptors modulate citalopram-induced serotonin release.
AB  - Previous studies suggest that noradrenaline may regulate serotonergic (5-HT)
      neurotransmission at the serotonin cell body and noradrenaline nerve terminal.
      Using microdialysis coupled to HPLC, we investigated the effects of alpha1
      adrenoceptor manipulation on extracellular serotonin levels - in the ventral
      hippocampus, prefrontal cortex, and raphe nuclei - in the presence or absence of
      the serotonin reuptake inhibitor (SSRI), citalopram. Extracellular 5-HT levels
      from prefrontal cortex, ventral hippocampus and raphe nuclei were markedly
      increased following citalopram administration (3.0 mg/kg s.c.). In the prefrontal
      cortex and ventral hippocampus, local blockade of the alpha1-adrenoceptor (3.0
      microM prazosin infusion) significantly decreased this citalopram-induced
      increase in serotonin, while cirazoline (alpha1-adrenoceptor agonist) and
      reboxetine (noradrenaline reuptake inhibitor) further increased extracellular
      serotonin levels when administered systemically (0.02 mg/kg i.p. and 5.0 mg/kg
      s.c. respectively) or locally infused (10.0 microM and 1.0 microM respectively).
      Moreover, prazosin pre-infusion into terminal areas prevented the increase in
      citalopram-induced increase in serotonin levels with systemic cirazoline or
      reboxetine administration. Prazosin also decreased the citalopram-induced
      increase in serotonin levels in the raphe nuclei; however no enhancement of the
      SSRI response was observed with systemic or local administration of cirazoline or
      reboxetine, suggesting that alpha1-adrenoceptors may already be maximally
      activated under these conditions. These data provide strong evidence that after
      acute citalopram administration, the alpha1-adrenoceptor exerts a modulatory role
      on serotonin levels.

PMID- 20043932
TI  - Right-sided spatial difficulties in ADHD demonstrated in continuous movement
      control.
AB  - Children with Attention Deficit Hyperactivity Disorder (ADHD) often show spatial
      attentional deficits, exhibiting a subtle rightwards bias, possibly due to
      dysfunction within the right hemisphere fronto-parietal network. Approximately
      50% of children with ADHD also show signs of movement dysfunction. The nature of
      this movement dysfunction and possible interactions with spatial attention
      difficulties has not been clearly described. This study compared 31 children with
      and 31 children without ADHD on a movement kinematic task that tested hand
      drawing movement precision. Participants used an electronic pen on a digitizing
      tablet. The pen tip position was sampled as X and Y coordinates at 200Hz. The
      task was to join targets of either 10 or 20mm diameter that were separated by a
      distance of 62.5 or 125 mm. Constant error in the X and Y planes, peak absolute
      velocity and acceleration, movement time, the number of pauses and pause time
      were analysed. Apart from a significantly increased rate of acceleration across
      all conditions, the children with ADHD demonstrated no temporal difficulties with
      the task; rather they showed subtle spatial difficulties, possibly suggestive of
      cerebellar involvement. The children with ADHD showed difficulties in accuracy of
      movement towards the right. They were less accurate in the X plane when moving
      towards the right-sided targets over the long distance. Greater variability in
      target accuracy was shown when moving towards the small target on the right side.
      The children with ADHD made significantly more pauses on the left target, when
      preparing the right movement, than the control group. These results suggest that
      the subtle spatial bias towards the right that has been demonstrated in ADHD in
      spatial attention also extends into the continuous movement domain.

PMID- 20043933
TI  - Dual effects of daidzein on chicken hepatic vitellogenin II expression and
      estrogen receptor-mediated transactivation in vitro.
AB  - Two in vitro systems were employed to delineate the estrogenic activity of
      daidzein (Da), alone or in combination with high or low concentrations of
      estrogen in two cell types possessing different estrogen-receptor (ER) isoforms,
      ERalpha and/or ERbeta: (1) vitellogenin II (VTG), the egg yolk precursor protein
      and the endpoint biomarker for estrogenicity, in chicken primary hepatocytes, and
      (2) CHO-K1 cells transiently co-transfected with ERalpha or ERbeta and estrogen
      response elements (ERE) linked to a luciferase reporter gene. Da (100 microM)
      alone induced VTG mRNA expression in chicken hepatocytes, albeit with much less
      potency compared to estradiol (E(2)). Da exhibited different effects in the
      presence of 1 microM and 10 microM E(2). At a concentration of 100 microM, Da
      enhanced 1 microM E(2)-induced VTG transcription by 2.4-fold, but significantly
      inhibited 10 microM E(2)-induced VTG mRNA expression in a dose-dependent fashion
      from 1 to 100 microM. Tamoxifen completely blocked the estrogenic effect of
      daidzein, alone or in combination with 1 microM of E(2), but did not influence
      its anti-estrogenic effect on 10 microM E(2)-induced VTG mRNA expression.
      Furthermore, neither E(2) nor daidzein, alone or in combination, affected ERalpha
      mRNA expression, yet all the treatments significantly up-regulated ERbeta mRNA
      expression in chicken hepatocytes. E(2) effectively triggered estrogen-response
      elements (ERE)-driven reporter gene transactivation in CHO-K1 cells expressing
      ERalpha or ERbeta and showed much greater potency with ERalpha than with ERbeta.
      In contrast, daidzein was 1000 times more powerful in stimulating ERbeta- over
      ERalpha-mediated transactivation. Daidzein, in concentrations ranging from 5 nM
      to 50 microM, did not affect ERbeta-mediated transactivation induced by 1 nM
      E(2), but it significantly inhibited ERbeta-mediated transactivation induced by
      10 nM E(2) at 500 nM. Despite the tremendous difference in sensitivity between
      the two in vitro systems, daidzein exhibited greater potency as an estrogen
      antagonist for ERbeta-mediated activity.

PMID- 20043934
TI  - Zinc protects human peripheral blood lymphocytes from Cr(III)(phenanthroline)3
      induced apoptosis.
AB  - We have studied the effect of Cr(III)(phen)3 [(tris(1,10-phenanthroline)
      chromium(III) chloride)] on lymphocytes in order to find out if metallothioneins
      (MTs) are produced in the process. We also investigated whether zinc pretreatment
      is able to protect cells from apoptosis reported to occur for this compound. Our
      results indicate that MT synthesis is induced by Cr(III)(phen)3, and it has been
      identified as the MT-3 isoform through RT-PCR which has not been reported
      earlier. By zinc pretreatment, this apoptosis is reversed as inferred from
      cytotoxicity studies, Annexin-V/PI staining, ethidium bromide/acridine orange
      staining and DNA fragmentation pattern and ultrastructural investigations using
      TEM and SEM. The zinc pretreatment reduces the amount of ROS produced by
      Cr(III)(phen)3. The MT-1a and 1b synthesized by zinc (also evidenced through RT
      PCR experiments) is possibly able to scavenge ROS which is one of the early
      signaling molecules that lead to apoptosis. Zinc pretreatment also reverses the
      changes in downstream signaling events such as mitochondrial membrane potential,
      ATP levels and the activation of caspase-3. This is the first report on the
      induction of MT-3 in lymphocytes due to a metal stress or any other stimuli. Even
      though MT-3 is synthesized here, apoptosis still occurs due to ROS production on
      Cr(III)(phen)3 exposure when the cells have not been primed with zinc.

PMID- 20043935
TI  - Poisoning of goats by the pods of Luetzelburgia auriculata.
AB  - Farmers report that the pods of Luetzelburgia auriculata cause digestive signs
      and death when ingested by goats. To demonstrate the toxicity of the pods of this
      plant 12 goats were divided into 4 groups of 3 goats each. Groups 1, 2, 3 and 4
      were administered 2.5, 1, 0.5 and nil g of pods per kg body weight, respectively.
      Goats in Groups 1 and 2 developed decreased ruminal movements followed by
      anorexia, depression and soft feces or diarrhea. Goats in Group 1 died 59-106 h
      after first showing clinical signs. Goats in Group 2 also regurgitated rumen
      content, but all recovered 65-90 h after first showing clinical signs. The only
      clinical sign shown by goats in Group 3 was regurgitation of rumen content, and
      all goats recovered 5.5-24 h after first regurgitating. All goats in Group 4
      remained normal. The goats that died were necropsied and found to have a reddish
      mucosa of the forestomachs that detached easily from the underlying tissues.
      Other lesions included diffuse reddening of the mucosa of the abomasum and
      intestine. Histological examination of the mucosa of the forestomachs showed
      diffuse ballooning degeneration of keratinocytes, with necrosis and vesicle and
      pustule formation in the epithelium. In some areas there was sloughing of the
      ruminal epithelium. These results demonstrate that the pods of L. auriculata are
      toxic and responsible for field outbreaks of poisoning in goats in the state of
      Piaui.

PMID- 20043936
TI  - Identification of a benthic microcystin-producing filamentous cyanobacterium
      (Oscillatoriales) associated with a dog poisoning in New Zealand.
AB  - In November 2008 a dog died soon after ingesting benthic "algal" mat material
      from the Waitaki River, New Zealand. Based on a morphological examination of
      environmental material, the causative organism was putatively identified as the
      filamentous cyanobacterium Phormidium sp. Two strains (VUW25 and CYN61) were
      isolated and cultured to enable further taxonomic and cyanotoxin
      characterisation. Phylogenetic analyses based on a region of the 16S rRNA gene
      sequence, intergenic spacer (ITS) region and the mcyE gene demonstrated that the
      species was likely to be a new Planktothrix species that is either benthic or has
      a biphasic life cycle. Using liquid chromatography-mass spectrometry (LC-MS),
      microcystin-LR, [D-Asp(3), Dha(7)] microcystin-LR, [D-Asp(3)] microcystin-LR, and
      minor proportions of [D-Asp(3), ADMAdda(5)] microcystin-LhR were identified. This
      is the first report of [D-Asp(3)] microcystin-LR, [D-Asp(3), Dha(7)] microcystin
      LR and an ADMAadda variant in New Zealand. No cylindrospermopsins, saxitoxins or
      anatoxins were detected. Dog deaths caused by the consumption of cyanobacterial
      mats containing anatoxins have previously been reported in New Zealand. To our
      knowledge, however, this is the first instance of a benthic microcystin-producing
      species causing an animal death in New Zealand.

PMID- 20043937
TI  - Distribution of homologous proteins to puffer fish saxitoxin and tetrodotoxin
      binding protein in the plasma of puffer fish and among the tissues of Fugu
      pardalis examined by Western blot analysis.
AB  - Puffer fish saxitoxin and tetrodotoxin binding protein (PSTBP) is a glycoprotein
      (200 kDa as a dimer) that we previously isolated from the plasma of Fugu pardalis
      (Yotsu-Yamashita et al., 2001). For the study on functions of PSTBP, here we
      examined distribution of homologous proteins to PSTBP in the plasma of seven
      species of puffer fish, and among the tissues of F. pardalis by Western blot
      analysis probed with a polyclonal IgG against unglycosylated PSTBP1 expressed in
      Echelichia coli. One or two major positive broad bands were detected at 105-140
      kDa molecular weight range in the plasma (0.5 microg protein) of all species of
      puffer fish tested, while no band was detected in the plasma (5 microg protein)
      of fish other than puffer fish. Glycopeptidase F treated plasma of all species of
      puffer fish tested commonly showed the bands at approximately 42 kDa that was
      consistent to the molecular weight of unglycosylated PSTBP. These data suggest
      that puffer fish commonly possess glycoproteins homologous to PSTBP, but the
      sizes of N-glycan are specific to the species. Among soluble protein extracts (5
      microg protein) from the tissues of F. pardalis, PSTBP was detected in all
      tissues examined, most prominently in heart, skin, and gall.

PMID- 20043938
TI  - A combinatorial study of pose effects in unfamiliar face recognition.
AB  - The face inversion effect, evidence that humans possess a specialized system for
      face processing, and the (3/4) view advantage, evidence that a canonical
      viewpoint exists from which faces may be optimally recognized, are two commonly
      cited findings in the face processing literature. In this paper, the interaction
      of these effects is examined in a sequential matching paradigm in which
      unfamiliar faces are combinatorially randomized in pose across two dimensions
      (roll and yaw). Using large numbers of poses, trials and face stimuli, two
      experiments were conducted in which pose was either jointly or independently
      randomized between intervals. Results include that performance was modulated in a
      continuous fashion as each dimension was manipulated, that an offset-specific
      (3/4) advantage exists, that both specific study and test pose affect
      recognition, and that, for like offset, yaw rotation is more deleterious to
      performance than roll rotation. Response bias effects included that matched or
      reflective yaw led observers to employ a more liberal criterion.

PMID- 20043939
TI  - Specificity of fast perceptual learning in shape localisation tasks based on
      detection versus form discrimination.
AB  - Perceptual learning is defined as a long-lasting improvement of perception as a
      result of experience. Here we examined the role of task on fast perceptual
      learning for shape localisation either in simple detection or based on form
      discrimination in different visual submodalities, using identical stimulus
      position and stimulus types for both tasks. Thresholds for each submodality were
      identified by four-alternative-forced-choice tasks. Fast perceptual learning
      occurred for shape detection-based on luminance, motion and color differences but
      not for texture differences. In contradistinction, fast perceptual learning was
      not evident in shape localisation based on discrimination. Thresholds of all
      submodalities were stable across days. Fast perceptual learning seems to differ
      not only between different visual submodalities, but also across different tasks
      within the same visual submodality.

PMID- 20043941
TI  - Effects of cyclosporin A induced T-lymphocyte depletion on the course of avian
      Metapneumovirus (aMPV) infection in turkeys.
AB  - The avian Metapneumovirus (aMPV) causes an economically important acute
      respiratory disease in turkeys (turkey rhinotracheitis, TRT). While antibodies
      were shown to be insufficient for protection against aMPV-infection, the role of
      T-lymphocytes in the control of aMPV-infection is not clear. In this study we
      investigated the role of T-lymphocytes in aMPV-pathogenesis in a T-cell
      suppression model in turkeys. T-cell-intact turkeys and turkeys partly depleted
      of functional CD4(+) and CD8(+) T-lymphocytes by Cyclosporin A (CsA) treatment
      were inoculated with the virulent aMPV subtype A strain BUT 8544. CsA-treatment
      resulted in a significant reduction of absolute numbers of circulating CD4(+) and
      CD8alpha(+) T-lymphocytes by up to 82 and 65%, respectively (P<0.05). Proportions
      of proliferating T-cells within mitogen-stimulated peripheral blood mononuclear
      cells were reduced by similar levels in CsA-treated birds compared to untreated
      controls (P<0.05). CsA-treated turkeys showed delayed recovery from aMPV-induced
      clinical signs and histopathological lesions and a prolonged detection of aMPV in
      choanal swabs. The results of this study show that T-lymphocytes play an
      important role in the control of primary aMPV-infection in turkeys.

PMID- 20043940
TI  - Activation of immune-associated phospholipase A2 is functionally linked to
      Toll/Imd signal pathways in the red flour beetle, Tribolium castaneum.
AB  - Bacterial challenge enhances phospholipase A(2) (PLA(2)) activity, which in turn
      induces biosynthesis of various eicosanoids that mediate non-self recognition
      signal to immune effectors in insects. But, there is little information on how
      PLA(2) activity is controlled after the non-self recognition. A recent genome
      analysis of the red flour beetle, Tribolium castaneum, has annotated both Toll
      and Imd signal pathways that are presumably considered to specifically respond to
      different microbial infections to express specific antimicrobial peptides (AMPs).
      This study set up a hypothesis that PLA(2) activation is linked to Toll and Imd
      pathways in T. castaneum. Bacterial challenge to the larvae of T. castaneum
      induced expressions of Toll and Imd genes. Different AMP genes were induced in
      larvae infected with Gram-positive or -negative bacteria. RNA interference using
      double-stranded RNAs (dsRNAs) specific to different Toll and Imd genes showed
      differential inhibition of these AMP expressions, indicating that the Toll and
      Imd pathways play critical roles in the production of AMPs by specifically
      responding to various bacterial challenges in T. castaneum. These Toll and Imd
      immune signals are also linked to the activation of PLA(2) in T. castaneum.
      Activation of PLA(2) was significantly induced in response to bacterial
      challenge, but was inhibited by dsRNAs specific to different Toll and Imd genes.
      The activation of PLA(2) via Toll and Imd pathways could be explained by
      induction of PLA(2) gene expression because the dsRNA treatments of Toll and Imd
      genes suppressed the gene expression of PLA(2) in response to bacterial
      challenge. The functional links were further supported by an immunofluorescence
      assay of PLA(2) intracellular translocation. Upon bacterial challenge, hemocytes
      from control larvae showed intracellular translocation of their PLA(2)s near to
      cell membrane, but hemocytes from larvae treated with dsRNAs of the Toll and Imd
      genes did not show the translocation, at which the PLA(2)s appeared to be evenly
      spread in the cytoplasm. These results suggest that recognition of bacterial
      challenge initiates Toll and Imd pathways in T. castaneum, which subsequently
      induces the activation of immune-associated PLA(2)s as well as gene expression of
      various AMPs.

PMID- 20043942
TI  - Identification of key cytosolic kinases containing evolutionarily conserved
      kinase tyrosine-based inhibitory motifs (KTIMs).
AB  - We previously reported that SHP-1 regulates IRAK-1 activity by binding to an ITIM
      like motif found within its kinase domain, which we named kinase tyrosine-based
      inhibitory motif (KTIM). Herein, we further investigated the presence, number,
      location, and evolutionary time of emergence of potential KTIMs in many cytosolic
      kinases, all known to play important roles in the signalling and function of
      immune cells. We unveil that several kinases contain potential KTIMs, mostly
      located within their kinase domain and appearing predominantly at the level of
      early vertebrates becoming highly conserved thereafter. Regarding the KTIMs that
      were found conserved in both vertebrates and invertebrates, we provide
      experimental data suggesting that such motifs may have constituted readily
      available sites that performed new regulatory functions as soon as their binding
      partners (e.g. SHP-1) appeared in vertebrates. We thus propose KTIMs as novel
      regulatory motifs in kinases that function through binding to SH2 domain
      containing proteins such as SHP-1.

PMID- 20043943
TI  - Protective effect of rofecoxib and nimesulide against intra-striatal quinolinic
      acid-induced behavioral, oxidative stress and mitochondrial dysfunctions in rats.
AB  - Role of cyclooxygenase (COX) enzyme has been well documented in both
      physiological and pathological conditions. COX-1 and COX-2 converts arachidonic
      acid into prostaglandins. Non-selective inhibition of COXs produces undesirable
      effects, whereas selective COX-2 inhibition produces protective effects in
      various inflammatory diseases. Recently, cyclooxygenase (COX) inhibitors have
      been implicated as a neuroprotectant in the treatment of various
      neurodegenerative diseases. Quinolinic acid is an endogenous excitotoxin that
      causes neurotoxicity in diverse areas of the brain and produces motor
      dysfunction. Present study is an attempt to investigate the possible role of COX
      inhibitors (selective COX-2 inhibitor and preferential COX-2 inhibitors) against
      quinolinic acid-induced behavioral, oxidative stress and mitochondrial enzyme
      complex alterations in rats. Intra-striatal administration of quinolinic acid
      (300 nmol) caused significant reduction in body weight (9%), motor in
      coordination, oxidative damage [increased MDA (100%), nitrite concentration
      (195%), depleted SOD (71%), catalase levels (70%)] and alteration in
      mitochondrial enzyme complex activity (decreased complex I (50%), II (50%) and
      IV(62%)) as compared to sham operated animals. Chronic treatment with rofecoxib
      (10 and 20 mg/kg, p.o.) and nimesulide (10 and 20mg/kg, p.o.) significantly
      attenuated quinolinic acid-induced behavioral and biochemical alterations as
      compared to quinolinic acid 300 nmol treated group. Further, rofecoxib (10, 20
      mg/kg) and nimesulide (20 mg/kg) significantly restored mitochondrial enzyme
      complex activities in striatum as compared to quinolinic acid 300 nmol treated
      group. Present study highlights the therapeutic potential of cyclooxygenase
      inhibitors against quinolinic acid induced neurotoxicity.

PMID- 20043945
TI  - Acyl-coenzyme A binding domain containing 3 (ACBD3; PAP7; GCP60): an emerging
      signaling molecule.
AB  - Golgi body-mediated signaling has been linked to its fragmentation and
      regeneration during the mitotic cycle of the cell. During this process, Golgi
      resident proteins are released to the cytosol and interact with other signaling
      molecules to regulate various cellular processes. Acyl-coenzyme A binding domain
      containing 3 protein (ACBD3) is a Golgi protein involved in several signaling
      events. ACBD3 protein was previously known as peripheral-type benzodiazepine
      receptor and cAMP-dependent protein kinase associated protein 7 (PAP7), Golgi
      complex-associated protein of 60kDa (GCP60), Golgi complex-associated protein 1
      (GOCAP1), and Golgi phosphoprotein 1 (GOLPH1). In this review, we present the
      gene ontology of ACBD3, its relations to other Acyl-coenzyme A binding domain
      containing (ACBD) proteins, and its biological function in steroidogenesis,
      apoptosis, neurogenesis, and embryogenesis. We also discuss the role of ACBD3 in
      asymmetric cell division and cancer. New findings about ACBD3 may help understand
      this newly characterized signaling molecule and stimulate further research into
      its role in molecular endocrinology, neurology, and stem cell biology.

PMID- 20043947
TI  - Detection of brain-derived neurotrophic factor (BDNF) in rat blood and brain
      preparations using ELISA: pitfalls and solutions.
AB  - Quantification of endogenous brain-derived neurotrophic factor (BDNF) can be
      performed with an enzyme-linked immunosorbent assay (ELISA). Although BDNF has
      been determined in blood and brain preparations in numerous studies with ELISA
      kits, the methodological issues regarding measurements of BDNF concentrations in
      the blood and particularly in the brain have only been superficially
      investigated. We aimed at validating and optimizing the BDNF ELISA kit with
      respect to measurements in rat blood and brain samples. We found that the pre
      analytical conditions were critical for plasma samples, but not serum or whole
      blood samples. The intra- and inter-assay variation and the accuracy and yield of
      the BDNF ELISA kit in rat serum and brain tissue were conducted with the optimal
      dilutions of frontal cortex and hippocampus extract. The optimal dilutions of
      frontal cortex and hippocampus extracts were determined to be 20 and 120 times,
      and we established that the intra-assay coefficient of variation (CV%) was 8 in
      hippocampus and 2 in frontal cortex and serum. The inter-assay variation was also
      low with a CV% of 11 or less in hippocampus, frontal cortex, and serum. Finally,
      we found that the accuracy and yield of the BDNF measurements were high in serum
      and low in hippocampus and frontal cortex. We conclude that the BDNF ELISA kit
      determines serum BDNF accurately and with high reproducibility. Furthermore it
      can be used for measurement of BDNF in rat brain preparations when particular
      precautions are taken and in particular with care regarding the dilution of the
      brain tissue samples.

PMID- 20043944
TI  - Phosphoinositide phosphatases in cell biology and disease.
AB  - Phosphoinositides are essential signaling molecules linked to a diverse array of
      cellular processes in eukaryotic cells. The metabolic interconversions of these
      phospholipids are subject to exquisite spatial and temporal regulation executed
      by arrays of phosphatidylinositol (PtdIns) and phosphoinositide-metabolizing
      enzymes. These include PtdIns- and phosphoinositide-kinases that drive
      phosphoinositide synthesis, and phospholipases and phosphatases that regulate
      phosphoinositide degradation. In the past decade, phosphoinositide phosphatases
      have emerged as topics of particular interest. This interest is driven by the
      recent appreciation that these enzymes represent primary mechanisms for
      phosphoinositide degradation, and because of their ever-increasing connections
      with human diseases. Herein, we review the biochemical properties of six major
      phosphoinositide phosphatases, the functional involvements of these enzymes in
      regulating phosphoinositide metabolism, the pathologies that arise from
      functional derangements of individual phosphatases, and recent ideas concerning
      the involvements of phosphoinositide phosphatases in membrane traffic control.

PMID- 20043946
TI  - NG2 cells: Properties, progeny and origin.
AB  - The NG2 proteoglycan is a type 1-transmembrane protein expressed by a range of
      cell types within and outside the mammalian nervous system. NG2-expressing (NG2)
      cells are found in grey and white matter tracts of the developing and adult CNS
      and have previously been assumed to represent oligodendrocyte precursor cells:
      new work using transgenic mice has shown that NG2 cells generate
      oligodendrocytes, protoplasmic astrocytes and in some instances neurons in vivo.
      NG2 cells express GABAA receptors and the AMPA subtype of glutamate receptors.
      They make intimate contact to neurons prior to myelinating axons and also form
      electron-dense synaptic specialisations with axons in the cerebellum, cortex and
      hippocampus and with non-myelinated axons in the corpus callosum. These synaptic
      NG2 cells respond to neuronal release of glutamate and GABA. This neuron-glia
      interaction may thus regulate the differentiation and proliferation of NG2 cells.
      The C-terminal PDZ-binding motif of the NG2 protein binds several PDZ proteins
      including Mupp1, Syntenin and the Glutamate Receptor Interacting Protein (GRIP).
      Since GRIP can bind subunits of the AMPA receptors expressed by NG2 cells, the
      interaction between GRIP and NG2 may orientate the glial AMPA receptors towards
      sites of neuronal glutamate release. The origin, heterogeneity and function of
      NG2 cells as modulators of the neuronal network are important incompletely
      resolved questions.

PMID- 20043948
TI  - A novel decalcification method for adult rodent bone for histological analysis of
      peripheral-central nervous system connections.
AB  - Histological analysis of bone encased tissue is severely hampered by technical
      difficulties associated with sectioning calcified tissue. Cryosectioning of bone
      is possible but requires significant technical adaptation and expensive materials
      and is often time-consuming. Some decalcifying reagents in common use result in
      successful cryosectioning in less time but the integrity of the soft tissue of
      the spinal column is often compromised during processing. This can result in
      significant loss of cellular detail. In order to find a method that would allow
      cryosectioning of the bone without loss of structural integrity of the underlying
      soft tissue we assessed the efficacy of four different decalcifying reagents with
      respect to their effects on the cellular structure of the myelin of the grey and
      white matter of the spinal cord. The antigenic integrity of the spinal cord white
      matter was evaluated using tissue structural integrity and quality of myelin
      basic protein immunostaining. The result of this research shows that 6% TCA not
      only decalcifies intact spinal column suitably for cryosectioning but does so
      without compromising the antigenic integrity of the tissue. The ease of
      application, speed of processing and a favorable cost-effective profile were
      secondary benefits noted with the use of the 6% TCA decalcifying solution. The
      ability to utilize a decalcifying solution that allows for both histomorphometry
      and immunohistochemistry in the same spinal column segment represents a novel
      technique that will provide new insights into pathophysiological aspects and
      therapeutic approaches ispinal cord damage or disease.

PMID- 20043950
TI  - Increased serum concentration of immune cell derived microparticles in
      polymyositis/dermatomyositis.
AB  - Microparticles are recently recognized players of intercellular communication.
      They are involved in signal transduction, cell activation and apoptosis. Their
      importance is also suggested in autoimmune diseases such as rheumatoid arthritis
      and systemic sclerosis. We investigated the role of microparticles in
      polymyositis/dermatomyositis, a group of rare autoimmune diseases, characterized
      by specific skin lesions and muscle weakness. The plasma concentration of
      monocyte and lymphocyte derived microparticles of 20 patients with
      polymyositis/dermatomyositis and 20 healthy controls were determined by flow
      cytometry. The structure of microparticles was visualized by electron microscopy.
      Significantly elevated numbers of monocyte (CD14 positive), T-lymphocyte (CD3
      positive) and B-lymphocyte (CD19 positive) derived microparticles were found in
      the plasma samples of polymyositis/dermatomyositis patients, compared to healthy
      controls (p=0.001, 0.01 and 0.006, respectively). Furthermore, the plasma levels
      of monocyte and B-lymphocyte derived microparticles correlated with the manual
      muscle strength test (r=0.497, p=0.027; r=0.508, p=0.023; respectively). Patients
      with anti-Jo-1 antibody and lung involvement had significantly higher numbers of
      T- and B-lymphocyte and monocyte derived MPs (p=0.006, 0.012 and 0.007,
      respectively, for anti-Jo-1; p=0.013, 0.016 and 0.025, respectively, for lung
      involvement). After ultracentrifugation, CK activity could be detected only in
      traces in the resuspended pellet containing microparticles of healthy and
      diseased individuals. The electron microscopy revealed slightly different
      microparticles in the samples of patients with polymyositis/dermatomyositis.
      These results suggest that immune cell derived microparticles may contribute to
      the inflammatory process in polymyositis/dermatomyositis, however, CK-positive,
      possibly muscle derived microparticles do not seem to be present in the blood of
      patients with polymyositis/dermatomyositis.

PMID- 20043949
TI  - A 3D multi-modal and multi-dimensional digital brain model as a framework for
      data sharing.
AB  - Computer based three-dimensional reconstruction and co-registration of
      experimental data provide powerful tools for integration of observation derived
      from various technical approaches leading to better understanding of brain
      functions. Here we describe a method to build a 3D multi-modal and multi
      dimensional model of brain structures providing framework for data sharing. All
      image processing, registration and 3D reconstruction were performed using open
      source software IMOD package software and ImageJ. The reconstruction procedure is
      based on series of AChE and Nissl stained sections aligned to blockface pictures.
      Integration of experimental data into the reference model is achieved by co
      registration of Nissl sections of experimental brain cases by positioning
      landmarks on corresponding anatomical structures. To overcome the challenge of
      comparing for experimental sections with those of the reference model, adjustment
      of experimental model to the brain model was done section by section and limited
      to the structures of interest. For this adjustment we stress the use of
      cytoarchitectural criteria for accurate registration of anatomical structures and
      co-registration procedures.

PMID- 20043951
TI  - Performance of enterovirus genotyping targeting the VP1 and VP2 regions on non
      typeable isolates and patient specimens.
AB  - Culture and serotyping of human enteroviruses are time-consuming and labor
      intensive. Targeted nucleic acid sequencing has emerged as a powerful alternative
      to conventional methods. Many published genotyping assays use two-step reverse
      transcription and polymerase chain reaction (RT-PCR), nested PCR protocols,
      and/or reflexive testing algorithms. The performance of a one-step RT-PCR
      protocol, a more clinically practical approach, was evaluated. The VP1 and/or VP2
      region of archived enterovirus isolates (n=36, representing 32 serotypes),
      patient enterovirus isolates not typeable by immunofluorescence antibodies
      (n=50), and enterovirus from direct patient specimens (48 cerebrospinal fluid, 2
      plasma/serum, 1 blood) were amplified and sequenced for genotype identification.
      The analytical sensitivity of the genotyping assays was 100-fold less than
      detection by RT-PCR of the 5'-untranslated region. Thirty-four of 36 archived
      isolates could be genotyped by combining results of VP1 and VP2 target
      sequencing. Non-typeable isolates included 17 echovirus 18, 6 enterovirus 68, 6
      rhinovirus, and 7 which could not be classified further. From clinical specimens,
      23 of 51 (45%) could be identified using VP2 typing and the most common types
      were coxsackievirus B1, echovirus 30, and echovirus 6. Using a one-step RT-PCR
      without nesting, most enterovirus isolates and a subset of clinical samples with
      high viral titer could be genotyped.

PMID- 20043952
TI  - Sensitivity of 8 CE (European Community)-approved rapid disposable tests for anti
      HIV antibody detection during and after seroconversion.
AB  - We evaluated the sensitivity for the anti-HIV antibody detection of the 8 rapid
      disposable tests (RDTs) EC approved in 2008. METHODS: A panel of 100 native serum
      samples collected from HIV-1 subtype B or non-B, HIV-1 group O or HIV-2-infected
      patient and 3 commercial seroconversion panels were tested. 50 sera from HIV
      negative patients were included to blind reading and RDT specificity. RESULTS:
      All native samples HIV-1 subtype B were reactive; an HIV-1 non-B subtype gave
      false-negative results with 3 of the 8 tests. False-negative results on HIV-1
      group O samples were observed with one RDT. All the HIV-2 samples were detected.
      Seroconversion sample reactivity ranged from 60 to 86.7% according to the tests.
      CONCLUSION: Despite their lower performances relative to ELISA tests during the
      HIV seroconversion period, RDT may be of interest in case of chronic infection.

PMID- 20043953
TI  - Identification of hepatitis C virus genotype 2a replicon variants with reduced
      susceptibility to ribavirin.
AB  - Ribavirin (RBV), a nucleoside analogue, is used in the treatment of hepatitis C
      virus (HCV) infection in combination with interferons. However, potential
      mechanisms of RBV resistance during HCV replication remain poorly understood.
      Serial passage of cells harboring HCV genotype 2a replicon in the presence of RBV
      resulted in the reduced susceptibility of the replicon to RBV. Transfection of
      fresh cells with RNA from RBV-resistant replicon cells demonstrated that the RBV
      resistance observed is largely replicon-derived. Four major amino acid
      substitutions: T1134S in NS3, P1969S in NS4B, V2405A in NS5A, and Y2471H in NS5B
      region, were identified. Site-directed mutagenesis of these mutations into the
      replicon indicated that Y2471H plays a role in the reduced susceptibility to RBV
      and leads to decrease in replication fitness. The results, in addition to
      analysis of sequence database, suggest that HCV variants with reduced
      susceptibility to RBV identified are preferential to genotype 2a.

PMID- 20043954
TI  - TNF-NF-kappaB signaling mediates excessive somnolence in hemiparkinsonian rats.
AB  - Daytime somnolence is common in patients with Parkinson's disease (PD); however
      there is a lack of understanding of the cellular mechanisms involved in mediating
      these effects. It has been hypothesized that microglial activation and the
      subsequent increase of pro-inflammatory cytokines play an important role in the
      pathogenesis of PD. Because some cytokines are involved in the regulation of
      sleep, this study was designed to determine if tumor necrosis factor (TNF) and
      interleukin-1beta (IL-1beta), mediate daytime somnolence in the proteasome
      inhibitor (MG-132)-induced hemiparkinsonian rat model. Our results indicated that
      microglial activation caused the loss of dopaminergic neurons in the substantia
      nigra, and the expression of TNF-alpha, but not IL-1beta, increased in the
      midbrain and hypothalamus in MG-132-induced hemiparkinsonian rats. Slow-wave
      sleep (SWS) increased after the induction of hemiparkinsonism, but rapid eye
      movement (REM) sleep was not consistently altered. Application of the TNF
      receptor fragment (TNFRF) blocked hemiparkinsonism-induced SWS alteration,
      whereas the IL-1 receptor antagonist (IL-1ra) exhibited no effect. Increased
      nuclear translocation of NF-kappaB in the midbrain, and the blockade of SWS
      enhancement in MG-132-induced hemiparkinsonian rats by an inhibitor of NF-kappaB
      activation indicate that the TNF-NF-kappaB cascade is a critical mediator of MG
      132 hemiparkinsonian-induced sleep alteration. This observation suggests
      potential therapeutic interventions to target the excessive daytime somnolence in
      patients with PD.

PMID- 20043955
TI  - Latent learning in zebrafish (Danio rerio).
AB  - The zebrafish may represent an excellent compromise between system complexity and
      practical simplicity for behavioral brain research. It may be particularly
      appropriate for large scale screening studies whose aim is to identify mutants
      with altered phenotypes or novel compounds with particular efficacy. For example,
      the zebrafish may have utility in the analysis of the biological mechanisms of
      learning and memory. Although learning and memory have been extensively studied
      and hundreds of underlying molecular mechanisms have been identified, this number
      may represent only the fraction of genes involved in these complex brain
      functions. Thus large scale mutagenesis screens may have utility. In order for
      such screens to succeed, appropriate screening paradigms must be developed. The
      first step in this research is the characterization of learning and memory
      capabilities of zebrafish and the development of automatable tasks. Here we show
      that zebrafish is capable of latent learning, i.e. can acquire memory of their
      environment after being allowed to explore it. For example, we found experimental
      zebrafish that experienced an open left tunnel or an open right tunnel of a maze
      during the unrewarded exploration phase of the test to show the appropriate side
      bias during a probe trial when they had to swim to a group of conspecifics (the
      reward). Given that exploration of the maze does not require the presence of the
      experimenter and the probe trial, during which the subjects are video-recorded
      and their memory is tested, is short, we argue that the paradigm has utility in
      high-throughput screening.

PMID- 20043956
TI  - Characterization of the sleep architecture in two species of fruit bat.
AB  - Bats (Chiroptera) are the second-most abundant mammalian order in the world,
      occupying a diverse range of habitats and exhibiting many different life history
      traits. In order to contribute to this highly underrepresented group we describe
      the sleep architecture of two species of frugivorous bat, the greater short-nosed
      fruit bat (Cynopterus sphinx) and the lesser dawn fruit bat (Eonycteris spelaea).
      Electroencephalogram (EEG) and electromyogram (EMG) data were recorded from
      multiple individuals (>or=5) by telemetry over a 72-h period in a laboratory
      setting with light/dark cycles equivalent to those found in the wild. Our results
      show that over a 24-h period both species spent more time asleep than awake (mean
      15 h), less than previous reported for Chiroptera (20 h). C. sphinx spent
      significantly more of its non-rapid eye movement sleep (NREM) and rapid eye
      movement sleep (REM) quotas during the light phase, while E. spelaea divided its
      sleep-wake architecture equally between both light and dark phases. Comparing the
      sleep patterns of the two species found that C. sphinx had significantly fewer
      NREM and REM episodes than E. spelaea but each episode lasted for a significantly
      longer period of time. Potential hypotheses to explain the differences in the
      sleep architecture of C. sphinx with E. spelaea, including risk of predation and
      social interaction are discussed.

PMID- 20043957
TI  - Tryptophan depletion impairs object-recognition memory in the rat: reversal by
      risperidone.
AB  - Tryptophan depletion techniques are effective in reducing central serotonergic
      function and have been used to investigate its role in mood and cognition. In the
      present study a tryptophan-free diet was fed to Lister-hooded male rats
      chronically for 21 days to investigate the effect of lowering central serotonin
      concentration on cognition using the novel object-recognition paradigm.
      Chronically tryptophan-depleted rats had impaired object-recognition memory; this
      was accompanied by a reduction in central serotonin of 40-50% in the hippocampus,
      frontal cortex and striatum. In a subsequent experiment, the atypical
      antipsychotic, risperidone (0.2 mg/kg), but not the typical antipsychotic,
      haloperidol (0.1 mg/kg), administered i.p. 30 min prior to the retention test,
      significantly attenuated the chronic tryptophan depletion impairment. These data
      show that chronic lowering of central serotonin is associated with impaired
      cognitive performance, and that this can be reversed by the atypical
      antipsychotic, risperidone.

PMID- 20043958
TI  - Proteasomal inhibition upregulates the endogenous MAPK deactivator MKP-1 in human
      airway smooth muscle: mechanism of action and effect on cytokine secretion.
AB  - Asthma is a chronic inflammatory condition. Inhibition of the ubiquitin
      proteasome system offers promise as a anti-inflammatory strategy, being
      responsible for the degradation of key proteins involved in crucial cellular
      functions, including gene expression in inflammation (e.g. inhibitory IkappaB
      alpha and the endogenous MAPK deactivator - MKP-1). As MKP-1 inhibits MAPK
      mediated pro-remodeling functions in human airway smooth muscle (ASM; a pivotal
      immunomodulatory cell in asthma) in this study we investigate the effect of the
      proteasome inhibitor MG-132 on MKP-1 and evaluate the anti-inflammatory effect of
      MG-132 on cytokine secretion from ASM cells. Examining the time-course of
      induction of MKP-1 mRNA and protein by MG-132 (10microM) we show that MKP-1 mRNA
      was first detected at 30min, increased to significant levels by 4h, resulting in
      a 12.6+/-1.5-fold increase in MKP-1 mRNA expression by 24h (P<0.05). MKP-1
      protein levels corroborate the mRNA results. Investigating the effect of MG-132
      on secretion of the cytokine IL-6 we show that while short-term pretreatment with
      MG-132 (30min) partially reduced TNFalpha-induced IL-6 via inhibition of IkappaB
      alpha degradation and the NF-kappaB pathway, longer-term proteasome inhibition
      (up to 24h) robustly upregulated MKP-1 and was temporally correlated with
      repression of p38-mediated IL-6 secretion from ASM cells. Moreover, utilizing a
      cytokine array we show that MG-132 represses the secretion of multiple cytokines
      implicated in asthma. Taken together, our results demonstrate that MG-132
      upregulates MKP-1 and represses cytokine secretion from ASM and highlight the
      potential of the proteasome as a therapeutic target in asthma.

PMID- 20043959
TI  - Polyplex nanomicelle promotes hydrodynamic gene introduction to skeletal muscle.
AB  - Skeletal muscle is an interesting target for gene therapy. To achieve effective
      gene introduction in skeletal muscle, a hydrodynamic approach by intravenous
      injection of plasmid DNA (pDNA) with transient isolation of the limb has
      attracted attention. In this study, we demonstrated that polyplex nanomicelle,
      composed of poly(ethyleneglycol) (PEG)-block-polycation and pDNA, showed
      excellent capacity of gene introduction to skeletal muscle. The evaluation of
      luciferase expression in the muscle revealed that the nanomicelle provided higher
      and sustained profiles of transgene expression compared with naked pDNA. Real
      time in vivo imaging using a video-rate confocal imaging system suggested that
      the nanomicelle showed tolerability in the intracellular environment, resulting
      in the slow but sustained transgene expression. The nanomicelle induced less
      TNFalpha induction in the muscle than naked pDNA, indicating the safety of
      nanomicelle-based gene delivery into the skeletal muscle. Moreover, the
      nanomicelle showed significant tumor growth suppression for almost a month by
      introducing a pDNA expressing a soluble form of vascular endothelial growth
      factor (VEGF) receptor-1 (sFlt-1) to skeletal muscle to obtain anti-angiogenic
      effect on tumor growth. This feature of sustained effect gives an important
      advantage of gene therapy, especially on the points of cost effectiveness and
      high compliance. These results suggest that the hydrodynamic gene introduction to
      skeletal muscle using polyplex nanomicelle system possesses the potential for
      effective gene therapy.

PMID- 20043960
TI  - Novel fibrillar insulin formulations for oral administration: Formulation and in
      vivo studies in diabetic mice.
AB  - The advantages of oral insulin are well-recognized, yet such formulations are
      still unavailable. Towards that goal we developed, and evaluated in diabetic ICR
      mice, two novel insulin microparticles for oral delivery. Although different in
      structure and shape, both microparticle formulations share: (i) hyaluronan on
      their surface (ii) fibrillar insulin, loaded at 50-100% efficiency over the
      insulin range of 1-10mg/ml and (iii) high retention of insulin loads in simulated
      gastro-intestinal environments. BGL values in diabetic ICR mice were tested over
      a time span of 8h, following a single oral dose of each formulation, using two
      protocols: the conventional (12h pre-fasting and 8h fasting); our revised
      protocol (no pre-fasting, meal at t=4h). In both protocols, initial blood glucose
      levels (BGL) were 400-600 mg/dL and the novel formulations generated a continuous
      reduction of BGL. Results in the revised protocol, that mimics human eating
      habits, were more pronounced, providing stable (over several hours) glucose
      reductions approaching non-diabetic BGL values. These two fibrillar insulin
      formulations, and the fibrillar form for therapeutic proteins, merit further
      studies.

PMID- 20043961
TI  - Threshold size for optimal passive pulmonary targeting and retention of rigid
      microparticles in rats.
AB  - The relationship between microparticle (MP) size and lung targeting efficiency,
      intra-lung distribution and retention time was systematically studied after
      intravenous administration of rigid fluorescent polystyrene MPs of various sizes
      (2, 3, 6 and 10 microm) to Sprague Dawley rats. Total fluorescence was assessed
      and it was found that 2 microm and 3 microm MPs readily passed through the lung
      to the liver and spleen while 10 microm MPs were completely entrapped in the lung
      for the one-week duration of the study. Approximately 84% of 6 microm MPs that
      were initially entrapped in the lung were cleared over the next 2 days and 15%
      were cleared over the remaining 5 days. A Caliper IVIS 100 small animal imaging
      system confirmed that 3 microm MPs were not retained in the lung but that 6
      microm and 10 microm MPs were widely distributed throughout the lung. Moreover,
      histologic examination showed MP entrapment in capillaries but not arterioles.
      These studies suggest that for rigid MPs the optimal size range required to
      achieve transient but highly efficiently targeting to pulmonary capillaries after
      IV injection is >6 microm but <10 microm in rats and that systemic administration
      of optimally sized MPs may be an efficient alternative to currently used
      inhalation-based delivery to the lung.

PMID- 20043962
TI  - Endocytic uptake of a large array of HPMA copolymers: Elucidation into the
      dependence on the physicochemical characteristics.
AB  - Endocytic uptake and subcellular trafficking of a large array of HPMA (N-(2
      hydroxypropyl)methacrylamide) based copolymers possessing positively or
      negatively charged residues, or hydrophobic groups were evaluated by flow
      cytometry and living cell confocal microscopy in cultured prostate cancer cells.
      The degrees of cellular uptake of various copolymer fractions with narrow
      polydispersities were quantified. The copolymer charge was the predominant
      physicochemical feature in terms of cellular uptake. Fast and efficient uptake
      occurred in positively charged copolymers due to non-specific adsorptive
      endocytosis, whereas slow uptake of negatively charged copolymers was observed.
      The uptake of copolymers was also molecular weight dependent. The copolymers were
      internalized into the cells through multiple endocytic pathways: positively
      charged copolymers robustly engaged clathrin-mediated endocytosis,
      macropinocytosis and dynamin-dependent endocytosis, while weakly negatively
      charged copolymers weakly employed these pathways; strongly negatively charged
      copolymers only mobilized macropinocytosis. HPMA copolymer possessing 4 mol% of
      moderately hydrophobic functional groups did not show preferential uptake. All
      copolymers ultimately localized in late endosomes/lysosomes via early endosomes;
      with varying kinetics among the copolymers. This study indicates that cell entry
      and subsequent intracellular trafficking of polymeric drug carriers are strongly
      dependent on the physicochemical characteristics of the nanocarrier, such as
      charge and molecular weight.

PMID- 20043963
TI  - High dietary supplement intakes among Flemish preschoolers.
AB  - The aim of this study was to determine the prevalence of dietary supplement use
      among Flemish preschoolers and to investigate associations between dietary
      supplement use and socio-economic variables of the parents. Parentally reported 3
      day estimated dietary records (n=696) were used to calculate mean daily nutrient
      intakes, using Software for Intake Distribution Estimation (Cside). Socio
      demographic information and frequency of dietary supplement use were collected
      via parental questionnaires, including a food frequency questionnaire (FFQ)
      (n=1847). The results from the FFQ revealed that more than 30% of the children
      used dietary supplements in the past month. Children of more highly educated
      parents and children of non-smokers were significantly more likely to use
      supplements than their counterparts. The types most frequently used were multi
      vitamin/mineral supplements. Except for vitamin D, mean dietary intakes derived
      from foods alone was higher than the minimum recommendations for both supplement
      and non-supplement users. The youngest group of supplement users even exceeded
      the tolerable upper intake level for zinc (7 mg). However, for vitamin D, dietary
      supplements could help meet dietary recommendations for this micronutrient. In
      conclusion, the results indicated that dietary supplement use by healthy children
      who typically achieve their micronutrient requirements by foods alone could cause
      excessive intakes. Future studies should investigate potential harms and benefits
      of dietary supplementation use among preschoolers.

PMID- 20043964
TI  - Confirmatory factor analysis of the Child Feeding Questionnaire among low-income
      African American families of preschool children.
AB  - This study examined the factor structure for three of the Child Feeding
      Questionnaire (CFQ) subscales, a widely used measure of parental feeding
      practices, among 296 low-income parents of African American preschool children.
      Confirmatory factor analysis showed an overall poor fit among CFQ subscales;
      Restriction, Pressure to Eat, and Concern about Child Weight, (chi(2),
      (df=87=300.249, CFI=1.00, NNFI=1.07, RMSEA=.091). Additionally, Cronbach's Alpha
      coefficients for 2 of the three subscales were below acceptable recommendations
      (Restriction=0.69; Pressure to Eat=0.58). These results suggest further
      psychometric clarification is needed to understand commonly reported feeding
      practice constructs among low-income African American mothers of preschool aged
      children.

PMID- 20043965
TI  - Temptations elicit compensatory intentions.
AB  - The compensatory beliefs model proposes that when faced with temptation, people
      form intentions to behaviourally compensate for indulgence. By creating a
      scenario in which female dieters were either faced with a tempting, high caloric
      food choice or not, this experiment tested the hypotheses that (1) dieters form
      compensatory intentions when experiencing the mental conflict of wanting to lose
      weight but also desiring to eat, and that (2) forming compensatory intentions
      results in the decision to indulge. Results supported the hypotheses, providing
      foundational validation for the compensatory beliefs model.

PMID- 20043966
TI  - Neuronal differentiation by analogs of staurosporine.
AB  - RGC-5 cells are transformed cells that express several surface markers
      characteristic of neuronal precursor cells, but resemble glial cells
      morphologically and divide in culture. When treated with the apoptosis-inducing
      agent staurosporine, RGC-5 cells assume a neuronal morphology, extend neurites,
      stop dividing, and express ion channels without acute signs of apoptosis. This
      differentiation with staurosporine is similar to what has been described for
      certain other neuronal cell lines, and occurs by a mechanism not yet understood.
      Inhibition of several kinases known to be inhibited by staurosporine fails to
      differentiate RGC-5 cells, and examination of the kinome associated with
      staurosporine-dependent differentiation has been unhelpful so far. To better
      understand the mechanism of staurosporine-mediated differentiation of neuronal
      precursor cells, we studied the effects of the following structurally similar
      molecules on differentiation of neuronal and non-neuronal cell lines, comparing
      them to staurosporine: 9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4
      i][1,6]benzodiazocine-10-carboxylic acid, 2,3,9,10,11,12-hexahydro-10-hydroxy-9
      methyl-1-oxo-, methyl ester, (9S,10R,12R)-(K252a), (5R,6S,8S)-6-hydroxy-5-methyl
      13-oxo-6,7,8,13,14,15-hexahydro-5H-16-oxa-4b,8a,14-triaza-5,8
      methanodibenzo[b,h]cycloocta[jkl]cyclopenta[e]-as-indacene-6-carboxylic acid
      (K252b), staurosporine aglycone (K252c), 7-hydroxystaurosporine (UCN-01), and 4'
      N-benzoylstaurosporine (PKC-412). Morphological differentiation, indicated by
      neurite extension and somal rounding, was quantitatively assessed with NeuronJ.
      We found that the critical structural component for differentiation in RGC-5
      cells is a basic amine adjacent to an accessible methoxy group at the 3' carbon.
      Given that UCN-01 and similar compounds are potent anti-cancer drugs, examination
      of molecules that share similar structural features may yield insights into the
      design of other drugs for differentiation.

PMID- 20043967
TI  - Metabotropic glutamate receptor 5, but not 1, modulates NMDA receptor-mediated
      activation of neuronal nitric oxide synthase.
AB  - In cerebellar neurons in culture, activation of group I metabotropic glutamate
      receptors (mGluRs) prevents glutamate and NMDA-induced neuronal death, indicating
      that it interferes with the excitotoxic mechanisms leading to death. However, it
      is not known which step of these mechanisms is affected by mGluRs. The aims of
      this work were to assess: (a) whether activation of group I mGluRs (mGluR1 or
      mGluR5) impairs NMDA-induced activation of the glutamate-nitric oxide-cGMP
      pathway; (b) which mGluR (1 or 5) is responsible for this impairment and (c)
      whether impairment of the pathway occurs at the level of activation of soluble
      guanylate cyclase by nitric oxide or of activation of neuronal nitric oxide
      synthase (nNOS) by NMDA. It is shown that activation of mGluR1 enhances the
      function of the glutamate-nitric oxide-cGMP pathway by increasing activation of
      soluble guanylate cyclase by nitric oxide. In contrast, mGluR5 activation
      inhibits the glutamate-nitric oxide-cGMP pathway by reducing NMDA-induced
      activation of nNOS. This is due to reduced NMDA-induced increase in cAMP, reduced
      activation of Akt by cAMP and of nNOS by Akt. The impairment of activation of the
      glutamate-NO-cGMP pathway by activation of mGluR5 would contribute to its
      neuroprotective effect against excitotoxicity in cerebellar neurons in culture.

PMID- 20043968
TI  - Protein kinase G type-Ialpha phosphorylates the apoptosis-regulating protein Bad
      at serine 155 and protects against apoptosis in N1E-115 cells.
AB  - Previous studies from our laboratory have shown that the cGMP/protein kinase G
      (PKG) signaling pathway plays an essential role in preventing spontaneous
      apoptosis in neural cells; however, the mechanism is not understood. A potential
      downstream target of PKG is the apoptosis-regulating protein Bad, which contains
      a sequence around its serine 155 (ser155 in mouse Bad, equivalent to ser118 in
      human Bad) predicted to be a consensus motif for PKG-catalyzed phosphorylation.
      Using both in vitro and cell-based experiments, we determined if PKG
      phosphorylates Bad at ser155 and if blocking/stimulating PKG-catalyzed Bad
      phosphorylation causes pro-apoptotic/anti-apoptotic responses. Recombinant PKG
      type-Ialpha (PKG-Ialpha) was found to directly phosphorylate recombinant Bad at
      ser155 in vitro. In N1E-115 mouse neural cells, which naturally express PKG
      Ialpha as the predominant PKG isoform, addition of 8-Br-cGMP (0.1-1.0 mM), a cell
      permeable direct PKG-Ialpha activator, increased ser155 phosphorylation of Bad.
      ODQ (50 microM), a soluble guanylyl cyclase inhibitor that lowers cGMP/PKG
      activity, decreased serum-induced ser155 phosphorylation of Bad and induced
      apoptosis in N1E-115 cells. Treatment with DT-2 and DT-3, selective PKG-Ialpha
      inhibitors, both decreased Bad ser155 phosphorylation and induced apoptosis. The
      data indicate that PKG-Ialpha directly phosphorylates Bad at ser155, which may
      participate in cGMP/PKG-induced anti-apoptotic/cytoprotective effects in neural
      cells.

PMID- 20043969
TI  - Safety evaluation of amylomaltase from Thermus aquaticus.
AB  - A recombinant amylomaltase, MQ-01, obtained by cultivation of Bacillus subtilis
      expressing the amylomaltase gene from Thermus aquaticus is to be used in the
      production of enzymatically-synthesized glycogen; which is intended for use as a
      food ingredient. In order to establish the safety of MQ-01, the enzyme was
      subjected to standard toxicological testing. In a battery of standard Salmonella
      typhimurium strains (TA98, TA100, TA1535, and TA1537) and in Escherichia coli WP2
      uvrA, both with and without metabolic activation, MQ-01 failed to exhibit
      mutagenic activity. Similarly, MQ-01 did not display clastogenic properties in
      Chinese hamster lung fibroblast cells (CHL/IU), in an in vitro chromosomal
      aberration assay. In a 13-week subchronic toxicity study in rats, oral
      administration of MQ-01 at doses of up to 15 mL/kg body weight/day (corresponding
      to approximately 1230 mg/kg body weight/day) did not produce compound-related
      clinical signs or toxicity, changes in body weight gain, food consumption,
      hematology, clinical chemistry, urinalysis, organ weights, or in any gross and
      microscopic findings. The results of this study support the safety of MQ-01 in
      food production.

PMID- 20043971
TI  - An alternative interpretation of, "A lifetime cancer bioassay of quinacrine
      administered into the uterine horns of female rats".
AB  - This companion article offers an alternative interpretation for the quinacrine
      induced uterine tumors observed in a 2-year bioassay in rats (CaBio, Cancel et
      al., 2010), and provides additional data from two new experiments that support a
      different interpretation and analysis. Our major premise is that the design of
      the Cancel et al. bioassay was flawed, particularly regarding dose selection that
      allowed for misinterpretation of carcinogenic activity. We feel the totality of
      the information provided herein dictates that the doses (70/70, 70/250 and 70/350
      mg/kg quinacrine) causing uterine tumors in their study clearly exceeded the
      maximum tolerated dose (MTD) typically administered in chronic cancer studies.
      Our new data support this conclusion and serve to explain the development of
      lesions, especially the uterine tumors, they have reported. We argue that the rat
      uterus is not a valid surrogate for the human fallopian tube. Further, we
      maintain that quinacrine is not genotoxic in vivo, as suggested in their paper.
      In summary, we believe that quinacrine is not carcinogenic in rats at doses that
      do not exceed the MTD.

PMID- 20043970
TI  - Toxicological evaluation of a dietary supplement formulated for male sexual
      health prior to market release.
AB  - The dietary supplement, 112 Degrees, was formulated with the goal of supporting
      sexual functioning in men. Due to rampant problems with drug adulteration for
      this category of products, a comprehensive screening for active pharmaceutical
      agents, with an emphasis on drugs prescribed for erectile dysfunction such as
      type 5 phosphodiesterase (PDE-5) inhibitors, and known unapproved PDE-5 drug
      analogues, was performed along with preclinical toxicology studies prior to the
      introduction of this product into the marketplace. 112 Degrees was found to be
      free of all pharmaceutical adulterants tested, and was not mutagenic,
      clastogenic, or genotoxic as demonstrated by the Ames test, chromosomal
      aberration assay, and mouse micronucleus assay, respectively. The LD(50) in the
      14-day acute oral toxicity study was greater than 5000 mg/kg, the highest dose
      tested.

PMID- 20043972
TI  - Development of TEFs for PCB congeners by using an alternative biomarker--thyroid
      hormone levels.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous toxic contaminants. Health risk
      assessment for this class of chemicals is complex: the current toxic equivalency
      factor (TEF) method covers dioxin-like (DL-) PCBs, dibenzofurans, and dioxins,
      but excludes non-DL-PCBs. To address this deficiency, we evaluated published data
      for several PCB congeners to determine common biomarkers of effect. We found that
      the most sensitive biomarkers for DL-non-ortho-PCB 77 and PCB 126 are liver
      enzyme (e.g., ethoxyresorufin-O-deethylase, EROD) induction, circulating
      thyroxine (T4) decrease, and brain dopamine (DA) elevation. For DL-ortho-PCB 118
      and non-DL-ortho-PCB 28 and PCB 153, the most sensitive biomarkers are brain DA
      decrease and circulating T4 decrease. The only consistent biomarker for both DL-
      and non-DL-PCBs is circulating T4 decrease. The calculated TEF-(TH), based on the
      effective dose to decrease T4 by 30% (ED(30)) with reference to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), is identical to both TEF-(WHO98) and TEF
      (WHO05) for TCDD and DL-PCBs (correlation coefficients are r=1.00, P<0.001; and
      r=0.99, P<0.001, respectively). We conclude that T4 decrease is a prospective
      biomarker for generating a new TEF scheme which includes some non-DL-congeners.
      The new TEF-(TH) parallels the TEF-(WHO) for DL-PCBs and, most importantly, is
      useful for non-DL-PCBs in risk assessment to address thyroid endocrine disruption
      and potentially the neurotoxic effects of PCBs.

PMID- 20043973
TI  - Setting of commercial glass ionomer cement Fuji IX by (27)Al and (19)F MAS-NMR.
AB  - OBJECTIVES: To investigate the long term setting reaction in the glass ionomer
      restorative, Fuji IX, by monitoring the structural evolution of aluminium and
      fluorine species using (27)Al and (19)F MAS-NMR spectroscopy. METHODS: Fuji IX
      cements aged from 5min up to 3 months were prepared according to the manufacturer
      instructions from the commercial material. The (27)Al and (19)F MAS-NMR studies
      were carried out on powders made after terminating the setting reaction. RESULTS:
      (27)Al MAS-NMR results show conversion of aluminium from the glass phase, where
      it has coordination number four, Al(IV), into the cement matrix where it has a
      coordination number of six, Al(VI). At least two different Al(VI) species were
      detected at short ageing time cements. Assignment of these species is discussed
      and compared with the data from other sources. The possibility for a condensed
      aluminium species [Al(13)(OH)(24)(H(2)O)(12)](7+) to form is considered. The
      ratio of aluminium in the cement, Al(VI), to the remaining unreacted in glass has
      been evaluated by deconvolution of the spectra. Various theoretical ratios of
      aluminium species in the cement matrix to the unreacted ones remaining in glass
      have been estimated. The (19)F MAS-NMR spectra are identical for the glass and
      cements at the early times and contain a dominant signal assigned to Al-F-Sr(n).
      CONCLUSIONS: The data confirms that the conversion of aluminium is a diffusion
      controlled process at early stage less than 1h and it is largely complete between
      1 and 6h. The comparison with the experimental data shows that the majority of
      aluminium cations do not form tricarboxylates but are coordinated with one or two
      carboxylic groups and other ligands. Insufficient amount of water and excess of
      glass in this cement formulation affect glass degradation mechanism.

PMID- 20043974
TI  - Depression-like state in maternal rats induced by repeated separation of pups is
      accompanied by a decrease of cell proliferation and an increase of apoptosis in
      the hippocampus.
AB  - Stressful experiences, such as an unsatisfactory mother-infant relationship after
      delivery, can induce depressive disorders, and it is well-known that stressors
      impair memory function. The hippocampus plays a crucial role in memory processes.
      In the present study, we determined whether a depressed-like state induced by
      repeated separation of pups affects the memory capability of the maternal rats.
      We also determined the effects of repeated separation from pups on cell
      proliferation, apoptosis, and serotonin expression in the brains of maternal
      rats. In the present results, the immobility time in the forced swim test was
      increased and the climbing time was decreased in the mothers separated from their
      pups. The latency in the step-down avoidance task was increased in the mothers
      separated from their pups. Also, the expressions of serotonin (5
      hydroxytryptamine) and tryptophan hydroxylase in the dorsal raphe were decreased
      in the mothers separated from their pups. The number of Ki-67-positive cells was
      decreased, while the number of terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL)-positive cells in the hippocampal dentate gyrus
      was increased in the mothers separated from their pups. Based on the present
      results, it is suggested that separation of pups might induce a depressed-like
      state in the maternal rats with reduced cell proliferation and increased
      apoptosis in the hippocampus, resulting in memory impairment of maternal rats.

PMID- 20043975
TI  - Apoptosis is directly related to intracellular amyloid accumulation in a cell
      line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of
      Down syndrome.
AB  - Human Down syndrome (DS) represents the most frequent cause of mental retardation
      associated to a genetic condition. DS also exhibits a characteristic early onset
      of neuropathology indistinguishable from that observed in Alzheimer's disease
      (AD), namely the deposition of the beta-amyloid peptide. Early endosomal
      dysfunction has been described in individuals with DS and AD, suggesting an
      important role of this subcellular compartment in the onset and progression of
      the pathology. On the other hand, cholesterol activates the amyloidogenic
      processing pathway for the amyloid precursor protein, and the lipoprotein
      receptor-related peptide interacts with the beta-amyloid peptide. In the present
      work, using cell lines derived from the cortex of both normal and trisomy 16 mice
      (Ts16), an animal model of DS, we showed that the application of exogenous beta
      amyloid has cytotoxic effects, expressed in decreased viability and increased
      apoptosis. Supplementation of the culture media with cholesterol associated to
      lipoprotein increased cell viability in both cell lines, but apoptosis decreased
      only in the normal cell line. Further, intracellular beta-amyloid content was
      elevated in trisomic cells following cholesterol treatment, with higher values in
      the trisomic cell line. Immunocytochemical detection showed intracellular
      accumulation of exogenous beta-amyloid in Rab4-positive compartments, which are
      known to be associated to endosomal recycling. The results suggest that the
      intracellular beta-amyloid pool plays a central role in apoptosis-mediated cell
      death in the trisomic condition.

PMID- 20043976
TI  - Pulpar tooth injury induces plastic changes in S100B positive astroglial cells in
      the trigeminal subnucleus caudalis.
AB  - Pain in humans constitutes a complex perception that involves peripheral tissues,
      nerves and the central nervous system. The glia is thought to be involved in the
      propagation and modulation of painful stimuli, as well as for the
      neurotransmission and plastic changes. In this work, an intermediate inflammatory
      nociceptive stimulus was generated after the exposure of the pulp in the left
      mandibular first molar. We analyzed the relationship between this tooth injury
      and the S100B expression in the trigeminal subnucleus caudalis. A significant
      difference of S100B immunoreactivity between the ipsilateral and the
      contralateral side could be observed at the 4th postoperative day. Besides, S100B
      positive-astrocytes located in the ipsilateral side showed an increase in their
      arborization, but not in the level of expression of the S100B protein. Our
      findings suggest that a unilateral peripheral nociceptive stimulus produces
      modifications in S100B positive-astrocytes in both sides of the trigeminal
      subnucleus caudalis.

PMID- 20043977
TI  - Possible involvement of NO/NOS signaling in hippocampal amyloid-beta production
      induced by transient focal cerebral ischemia in aged rats.
AB  - In the present study, to define the roles of nitric oxide (NO) signaling in
      amyloid-beta (A beta) production after transient cerebral ischemia, extracellular
      levels of NO and A beta were monitored by intracerebral microdialysis in the
      hippocampus of aged rats exposed to transient middle cerebral artery occlusion
      and reperfusion (MCAO/R). The results indicated that 1-h MCAO significantly
      upregulated hippocampal NO and A beta levels. In addition, the NO elevation
      preceded the A beta changes. The Western blotting suggested that acute
      hypoperfusion could increase the expression of beta-secretase 1 (BACE1) but not
      BACE2. The enhanced NO concentration in acute stage of MCAO/R was coincident with
      increased eNOS expression, while in subacute stage was coincident with increased
      iNOS and nNOS. Our results also indicated that pretreatment of L-NAME, one non
      selective NOS inhibitor could decrease the BACE1 expression, reverse both NO and
      A beta changes and rescue the delayed neuronal death. These preliminary findings
      indicated that activation of NOS/NO signaling system could trigger A beta
      production through BACE1 pathway during acute ischemic episode. The present data
      may be important in understanding, at least in part, the pathological role of
      NO/NOS system involved in hippocampal A beta production and neuronal damage
      induced by transient cerebral ischemia.

PMID- 20043978
TI  - Fasudil, a Rho-kinase inhibitor, attenuates induction and progression of cerebral
      aneurysms: experimental study in rats using vascular corrosion casts.
AB  - Fasudil (a Rho-kinase inhibitor) has been shown to attenuate abdominal aortic
      aneurysm development, but any preventive effect against development of cerebral
      aneurysms is unclear. The effect of fasudil on the development of cerebral
      aneurysms was investigated in 55 female Sprague-Dawley rats divided into 4
      groups: Group 1 (n=10) was the control group without treatment. Groups 2-4 (n=15
      each) were subjected to cerebral aneurysm induction procedures plus 1% NaCl in
      the drinking water. Groups 3 and 4 were also treated with 0.5 or 1.0mg/mL of
      fasudil in the drinking water, respectively. Vascular corrosion casts of the
      cerebral arteries were prepared and examined using a scanning electron microscope
      after 2 months. No significant differences were observed in the degree of induced
      hypertension between Groups 2, 3 and 4. No aneurysms were found in Group 1.
      Examination of the left anterior cerebral-olfactory artery junction, which is the
      most susceptible site for aneurysm development, found significantly fewer
      aneurysmal lesions in Groups 3 (60%) and 4 (53%) compared to Group 2 (100%)
      (P<0.02). This study suggests that fasudil attenuated induction of cerebral
      aneurysms in the rat model.

PMID- 20043979
TI  - Acupuncture suppresses morphine self-administration through the GABA receptors.
AB  - The neurobiological substrate for morphine self-administration in animals is
      believed to involve the dopamine system of the nucleus accumbens. Our previous
      study has shown that acupuncture at the acupoint Shenmen (HT7) reduced dopamine
      release in the nucleus accumbens and behavioral hyperactivity induced by systemic
      administration of morphine. Here we investigated the effect of acupuncture on
      morphine self-administration and potential roles of GABA receptors in the
      mechanisms behind acupuncture. Male Sprague-Dawley rats were trained to self
      administer morphine (0.1 mg/kg per infusion) during daily 1-h session under fixed
      ratio 1 schedule. Following the stable responding on morphine self
      administration, acupuncture was applied to HT7 points bilaterally (1 min) prior
      to the testing session. Another groups of rats were given the GABA(B) receptor
      antagonist SCH 50911 (3.0 mg/kg, i.p.), the GABA(A) receptor antagonist
      bicuculline (1.0 mg/kg, i.p.) or saline 30 min prior to the acupuncture
      treatment. We have found that acupuncture at the acupoint HT7, but not at the
      control point Yangxi (LI5), significantly decreased morphine self-administration.
      Moreover, either SCH 50911 or bicuculline blocked the inhibitory effects of
      acupuncture on morphine self-administration. Taken together, the current results
      suggest that acupuncture at specific HT7 points regulates the reinforcing effects
      of morphine via regulation of GABA receptors.

PMID- 20043980
TI  - The contribution of calcium/calmodulin-dependent protein-kinase II (CaMKII) to
      short-term plasticity at the neuromuscular junction.
AB  - Calcium/calmodulin-dependent protein-kinase II (CaMKII) is a ubiquitous
      intracellular enzyme, which is implicated in learning and memory mechanisms in
      the central nervous system, however its contribution to peripheral cholinergic
      neurotransmission is not well characterized. This study evaluated the impact of
      CaMKII on the function of frog neuromuscular synapse using electrophysiological
      recordings. Application of the selective CaMKII inhibitor KN-93 (5 microM) did
      not significantly alter the parameters of evoked and spontaneous quantal
      acetylcholine release under low-frequency stimulation (0.03 Hz). KN-93, on the
      other hand, produced pronounced changes in short-term synaptic plasticity:
      particularly, KN-93 inhibits the second component of paired-pulse facilitation
      (interpulse intervals of 100 ms and longer) and strengthens the depression of
      synaptic transmission under high-frequency stimulation (50 Hz). These results
      imply that CaMKII plays an important role in presynaptic functions at the frog
      neuromuscular junction, and potentiates quantal acetylcholine release under high
      frequency activity.

PMID- 20043981
TI  - Evaluation of droplet velocity and size from nasal spray devices using phase
      Doppler anemometry (PDA).
AB  - To determine aerosol deposition during the inhalation drug delivery, it is
      important to understand the combination of velocity and droplet size together. In
      this study, phase Doppler anemometry (PDA) was used to simultaneously
      characterize the aerosol velocity and droplet size distribution (DSD) of three
      nasal spray pumps filled with water. Thirteen sampling positions were located in
      the horizontal cross-sectional area of the nasal spray plumes at a distance of
      3cm from the pump orifice. The results showed droplet velocities near the center
      of the spray plume were higher and more consistent than those near the edge. The
      pumps examined showed significant differences in their aerosol velocity at the
      center of the spray plume, which suggest that this metric might be used as a
      discriminating parameter for in vitro testing of nasal sprays. Droplet size
      measurements performed using PDA were compared with results from laser light
      scattering measurements. The ability of PDA to provide simultaneous measurements
      of aerosol velocity and size makes it a powerful tool for the detailed
      investigation of nasal spray plume characteristics.

PMID- 20043982
TI  - A novel method for the production of crystalline micronised particles.
AB  - The aim of this study was to develop a method for converting an amorphous drug to
      a crystalline form to enhance its stability and inhalation performance. Spray
      dried amorphous salbutamol sulphate powder was conditioned with supercritical
      carbon dioxide (scCO(2)) modified with menthol. The effect of menthol
      concentration, pressure, temperature and time on the characteristics of the
      resulting salbutamol sulphate powder was investigated. Pure scCO(2) had no effect
      on the physical properties of amorphous salbutamol sulphate; however, scCO(2)
      modified with menthol at 150bar and 50 degrees C was efficient in converting
      amorphous drug to crystalline form after 12h of conditioning. The average
      particle size of powders decreased slightly after the conditioning process
      because of reducing agglomeration between particles by increasing surface
      roughness. Emitted dose measured by the fine particle fraction (FPF(emitted)) of
      amorphous salbutamol sulphate was enhanced from 32% to 43% after conditioning
      with scCO(2)+menthol and its water uptake was significantly decreased. This study
      demonstrates the potential of scCO(2)+menthol for converting amorphous forms of
      powders to crystalline, while preserving the particle size.

PMID- 20043984
TI  - The anatomy of the Gottingen minipig hypothalamus.
AB  - The microscopic organization of the Gottingen minipig (sus scrofa) hypothalamus
      was studied using Nissl stain, acetylcholinesterase histochemistry, and
      immunohistochemical staining for calretinin, tyrosin hydroxylase, oxytocin,
      vasopressin, and orexin A. Mediolaterally the minipig hypothalamus can be divided
      into three cytoarchitectonic distinct longitudinal zones. The periventricular
      longitudinal zone comprises the supraoptic, paraventricular, median preoptic,
      anteroventral periventricular, suprachiasmatic and arcuate nuclei. The medial
      longitudinal zone includes the prominent medial preoptic, ventromedial,
      dorsomedial and medial mammillary nuclei. Together with the anterior hypothalamic
      area, they can be further divided into distinct subregions. The dorsal and
      posterior hypothalamic areas and the retromammillary and lateral mammillary
      nuclei are cyto- and chemoarchitectonically distinct but cannot be further
      divided into subregions. The cell sparse, fiber rich lateral longitudinal zone
      comprises the lateral preoptic and lateral hypothalamic area as well as the
      perifornical, lateral tuberal and tuberomammillary nuclei. The findings presented
      here indicate that the cyto- and chemoarchitecture of the Gottingen minipig
      hypothalamus is comparable to that of rat, landrace pig, monkey, and human and
      that the Gottingen minipig may be well suited for future, non-primate, large
      mammal, hypothalamic research.

PMID- 20043983
TI  - Inflammation and social experience: an inflammatory challenge induces feelings of
      social disconnection in addition to depressed mood.
AB  - Although research has established links between feelings of social isolation and
      inflammation, the direction of these effects is unclear. Based on the role that
      proinflammatory cytokines play in initiating "sickness behavior," which includes
      symptoms such as social withdrawal, it is possible that inflammatory processes
      heighten feelings of 'social disconnection.' Here, we examined whether exposure
      to an inflammatory challenge increased self-reported feelings of social
      disconnection. In addition, because both inflammatory processes and feelings of
      social disconnection contribute to depressive symptoms, we also explored whether
      increases in feelings of social disconnection played a role in the link between
      inflammation and depressed mood. Participants were randomly assigned to either
      receive endotoxin, an inflammatory challenge, or placebo. Proinflammatory
      cytokines (IL-6, TNF-alpha) were collected at baseline and then hourly for 6h.
      Participants completed self-reports of sickness symptoms ("fatigue"), social
      disconnection ("I feel disconnected from others"), and depressed mood ("unhappy")
      hourly. Results revealed that endotoxin led to significant increases (from
      baseline) in IL-6 and TNF-alpha levels as well as feelings of social
      disconnection and depressed mood. Moreover, controlling for increases in social
      disconnection eliminated the relationship between exposure to inflammatory
      challenge and depressed mood. This study demonstrates that inflammation can have
      social psychological consequences, which may play a role in cytokine-related
      depressive symptoms.

PMID- 20043985
TI  - Carnosine protects against permanent cerebral ischemia in histidine decarboxylase
      knockout mice by reducing glutamate excitotoxicity.
AB  - Recently, we showed that carnosine protects against NMDA-induced excitotoxicity
      in differentiated PC12 cells through a histaminergic pathway. However, whether
      the protective effect of the carnosine metabolic pathway also occurs in ischemic
      brain is unknown. Utilizing the model of permanent middle cerebral artery
      occlusion (pMCAO) in mice, we found that carnosine significantly improved
      neurological function and decreased infarct size in both histidine decarboxylase
      knockout and the corresponding wild-type mice to the same extent. Carnosine
      decreased the glutamate levels and preserved the expression of glutamate
      transporter-1 (GLT-1) but not the glutamate/aspartate transporter in astrocytes
      exposed to ischemia in vivo and in vitro. It suppressed the dissipation of Delta
      Psi(m) and generation of mitochondrial reactive oxygen species (ROS) induced by
      oxygen-glucose deprivation in astrocytes. Furthermore, carnosine also decreased
      the mitochondrial ROS and reversed the decrease in GLT-1 induced by rotenone.
      These findings are the first to demonstrate that the mechanism of carnosine
      action in pMCAO may not be mediated by the histaminergic pathway, but by reducing
      glutamate excitotoxicity through the effective regulation of the expression of
      GLT-1 in astrocytes due to improved mitochondrial function. Thus, our study
      reveals a novel antiexcitotoxic agent in ischemic injury.

PMID- 20043986
TI  - Oxidative modification sensitizes mitochondrial apoptosis-inducing factor to
      calpain-mediated processing.
AB  - Although processing of mitochondrial apoptosis-inducing factor (AIF) is essential
      for its function during apoptosis in most cell types, the detailed mechanisms of
      AIF cleavage remain elusive. Recent findings indicate that the proteolytic
      process is Ca(2+)-dependent and that it is mediated by a calpain located in the
      mitochondrial intermembrane space. We can now report that, in addition to a
      sustained intracellular Ca(2+) elevation, enhanced formation of reactive oxygen
      species (ROS) is a prerequisite step for AIF to be cleaved and released from
      mitochondria in staurosporine-treated cells. These events occurred independent of
      the redox state of the mitochondria and were not influenced by binding of
      pyridine nucleotides to AIF. Chelation of cytosolic Ca(2+) by BAPTA/AM suppressed
      the elevation of both Ca(2+) and ROS, suggesting that the Ca(2+) rise was the
      most upstream signal required for AIF processing. We could further show that the
      stimulated ROS production leads to oxidative modification (carbonylation) of AIF,
      which markedly increases its rate of cleavage by calpain. Accordingly,
      pretreatment of the cells with antioxidants blocked AIF carbonylation, as well as
      its subsequent cleavage and release from the mitochondria. Combined, our data
      provide evidence that ROS-mediated, posttranslational modification of AIF is
      critical for its cleavage by calpain and thus for AIF-mediated cell death.

PMID- 20043987
TI  - Nitric oxide synthase-2 regulates mitochondrial Hsp60 chaperone function during
      bacterial peritonitis in mice.
AB  - Nitric oxide synthase-2 (NOS2) plays a critical role in reactive nitrogen species
      generation and cysteine modifications that influence mitochondrial function and
      signaling during inflammation. Here, we investigated the role of NOS2 in hepatic
      mitochondrial biogenesis during Escherichia coli peritonitis in mice. NOS2(-/-)
      mice displayed smaller mitochondrial biogenesis responses than Wt mice during E.
      coli infection according to differences in mRNA levels for the PGC-1 alpha
      coactivator, nuclear respiratory factor-1, mitochondrial transcription factor-A
      (Tfam), and mtDNA polymerase (Pol gamma). NOS2(-/-) mice did not significantly
      increase mitochondrial Tfam and Pol gamma protein levels during infection in
      conjunction with impaired mitochondrial DNA (mtDNA) transcription, loss of mtDNA
      copy number, and lower State 3 respiration rates. NOS2 blockade in mitochondrial
      GFP reporter mice disrupted Hsp60 localization to mitochondria after E. coli
      exposure. Mechanistically, biotin-switch and immunoprecipitation studies
      demonstrated NOS2 binding to and S-nitros(yl)ation of Hsp60 and Hsp70.
      Specifically, NOS2 promoted Tfam accumulation in mitochondria by regulation of
      Hsp60-Tfam binding via S-nitros(yl)ation. In hepatocytes, site-directed
      mutagenesis identified (237)Cys as a critical residue for Hsp60 S
      nitros(yl)ation. Thus, the role of NOS2 in inflammation-induced mitochondrial
      biogenesis involves both optimal gene expression for nuclear-encoded mtDNA
      binding proteins and functional regulation of the Hsp60 chaperone that enables
      their importation for mtDNA transcription and replication.

PMID- 20043988
TI  - Regulation of phagocyte NADPH oxidase by hydrogen peroxide through a Ca(2+)/c-Abl
      signaling pathway.
AB  - The importance of H(2)O(2) as a cellular signaling molecule has been demonstrated
      in a number of cell types and pathways. Here we explore a positive feedback
      mechanism of H(2)O(2)-mediated regulation of the phagocyte respiratory burst
      NADPH oxidase (NOX2). H(2)O(2) induced a dose-dependent stimulation of superoxide
      production in human neutrophils, as well as in K562 leukemia cells overexpressing
      NOX2 system components. Stimulation was abrogated by the addition of catalase,
      the extracellular Ca(2+) chelator BAPTA, the T-type Ca(2+) channel inhibitor
      mibefradil, the PKCdelta inhibitor rottlerin, or the c-Abl nonreceptor tyrosine
      kinase inhibitor imatinib mesylate or by overexpression of a dominant-negative
      form of c-Abl. H(2)O(2) induced phosphorylation of tyrosine 311 on PKCdelta and
      this activating phosphorylation was blocked by treatment with rottlerin, imatinib
      mesylate, or BAPTA. Rac GTPase activation in response to H(2)O(2) was abrogated
      by BAPTA, imatinib mesylate, or rottlerin. In conclusion, H(2)O(2) stimulates
      NOX2-mediated superoxide generation in neutrophils and K562/NOX2 cells via a
      signaling pathway involving Ca(2+) influx and c-Abl tyrosine kinase acting
      upstream of PKCdelta. This positive feedback regulatory pathway has important
      implications for amplifying the innate immune response and contributing to
      oxidative stress in inflammatory disorders.

PMID- 20043989
TI  - Chronic in utero buprenorphine exposure causes prolonged respiratory effects in
      the guinea pig neonate.
AB  - Our laboratory studies the effects of in utero opioid exposure on the neonate. In
      this work we test the effects of chronic in utero exposure to buprenorphine on
      the neonate. Buprenorphine is a promising candidate for treatment of opioid
      addiction during pregnancy and it has been suggested to decrease the neonatal
      abstinence syndrome in human infants. In our guinea pig model, we focused not
      only on the respiratory effects of in utero exposure on the neonate, but also
      studied withdrawal signs in the neonate, a major concern of all opioid treatment
      during pregnancy. Pregnant guinea pigs were treated with daily subcutaneous
      injections of 0.1mg/kg buprenorphine during the second half of gestation. We
      measured weight, locomotor activity and respiratory function in pups of ages 3 to
      14 days. Respiratory response was recorded using a two-chamber plethysmograph,
      while pups were breathing either room air or 5% CO(2). Our results show that
      chronic in utero exposure to buprenorphine induces respiratory effects up to day
      14 after birth, while earlier studies have shown that effects of either in utero
      methadone or morphine only persist in the first week after birth in the guinea
      pig model. These data provide important information for clinical trials of
      buprenorphine treatment suggesting that duration and severity of respiratory
      effects of in utero buprenorphine exposure should be monitored.

PMID- 20043990
TI  - Agonist-dependent mu-opioid receptor signaling can lead to heterologous
      desensitization.
AB  - Desensitization of the micro-opioid receptor (MOR) has been implicated as an
      important regulatory process in the development of tolerance to opiates.
      Monitoring the release of intracellular Ca(2+) ([Ca(2+)](i)), we reported that [D
      Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO)-induced receptor
      desensitization requires receptor phosphorylation and recruitment of beta
      arrestins (betaArrs), while morphine-induced receptor desensitization does not.
      In current studies, we established that morphine-induced MOR desensitization is
      protein kinase C (PKC)-dependent. By using RNA interference techniques and
      subtype specific inhibitors, PKCepsilon was shown to be the PKC subtype activated
      by morphine and the subtype responsible for morphine-induced desensitization. In
      contrast, DAMGO did not increase PKCepsilon activity and DAMGO-induced MOR
      desensitization was not affected by modulating PKCepsilon activity. Among the
      various proteins within the receptor signaling complex, Galphai2 was
      phosphorylated by morphine-activated PKCepsilon. Moreover, mutating three
      putative PKC phosphorylation sites, Ser(44), Ser(144) and Ser(302) on Galphai2 to
      Ala attenuated morphine-induced, but not DAMGO-induced desensitization. In
      addition, pretreatment with morphine desensitized cannabinoid receptor CB1
      agonist WIN 55212-2-induced [Ca(2+)](i) release, and this desensitization could
      be reversed by pretreating the cells with PKCepsilon inhibitor or overexpressing
      Galphai2 with the putative PKC phosphorylation sites mutated. Thus, depending on
      the agonist, activation of MOR could lead to heterologous desensitization and
      probable crosstalk between MOR and other Galphai-coupled receptors, such as the
      CB1.

PMID- 20043992
TI  - Structural insights into interferon regulatory factor activation.
AB  - The interferon regulatory factors (IRFs) play important roles in development of
      the immune system and host defense. Recent crystallographic and biochemical
      studies have provided insights into the mechanism of activation of IRFs by
      phosphorylation. The activation of a latent closed conformation of IRF in the
      cytoplasm is triggered by phosphorylation of Ser/Thr residues in a C-terminal
      region. Phosphorylation stimulates the C-terminal autoinhibitory domain to attain
      a highly extended conformation triggering dimerization through extensive contacts
      to a second subunit. Dimers are then transported into the nucleus and assemble
      with the coactivator CBP/p300 to activate transcription of type I interferons and
      other target genes. The advances made in understanding the release of inhibition
      after IRF dimerization have generated a detailed structural model of how IRFs
      signaling pathways are activated.

PMID- 20043991
TI  - Viagra for your synapses: Enhancement of hippocampal long-term potentiation by
      activation of beta-adrenergic receptors.
AB  - Beta-adrenergic receptors (beta-ARs) critically modulate long-lasting synaptic
      plasticity and long-term memory storage in the mammalian brain. Synaptic
      plasticity is widely believed to mediate memory storage at the cellular level.
      Long-term potentiation (LTP) is one type of synaptic plasticity that has been
      linked to memory storage. Activation of beta-ARs can enhance LTP and facilitate
      long-term memory storage. Interestingly, many of the molecular signaling pathways
      that are critical for beta-adrenergic modulation of LTP mirror those required for
      the persistence of memory. In this article, we review the roles of signaling
      cascades and translation regulation in enabling beta-ARs to control expression of
      long-lasting LTP in the rodent hippocampus. These include the cyclic-AMP/protein
      kinase-A (cAMP-PKA) and extracellular signal-regulated protein kinase cascades,
      two key pathways known to link transmitter receptors with translation regulation.
      Future research directions are discussed, with emphasis on defining the roles of
      signaling complexes (e.g. PSD-95) and glutamatergic receptors in controlling the
      efficacy of beta-AR modulation of LTP.

PMID- 20043994
TI  - VANGL1 rare variants associated with neural tube defects affect convergent
      extension in zebrafish.
AB  - In humans, rare non-synonymous variants in the planar cell polarity gene VANGL1
      are associated with neural tube defects (NTDs). These variants were hypothesized
      to be pathogenic based mainly on genetic studies in a large cohort of NTD
      patients. In this study, we validate the potential pathogenic effect of these
      mutations in vivo by investigating their effect on convergent extension in
      zebrafish. Knocking down the expression of tri, the ortholog of Vangl2, using an
      antisense morpholino (MO), as shown previously, led to a defective convergent
      extension (CE) manifested by a shortened body axis and widened somites. Co
      injection of the human VANGL1 with the tri-MO was able to partially rescue the
      tri-MO induced phenotype in zebrafish. In contrast, co-injection of two human
      VANGL1 variants, p.Val239Ile and p.Met328Thr, failed to rescue this phenotype. We
      next carried out overexpression studies where we measured the ability of the
      human VANGL1 alleles to induce a CE phenotype when injected at high doses in
      zebrafish embryos. While overexpressing the wild-type allele led to a severely
      defective CE, overexpression of either p.Val239Ile or p.Met328Thr variant failed
      to do so. Results from both tri-MO knockdown/rescue results and overexpression
      assays suggest that these two variants most likely represent "loss-of-function"
      alleles that affect protein function during embryonic development. Our study
      demonstrates a high degree of functional conservation of VANGL genes across
      evolution and provides a model system for studying potential variants identified
      in human NTDs.

PMID- 20043995
TI  - pH effects on the hyaluronan hydrolysis catalysed by hyaluronidase in the
      presence of proteins: Part I. Dual aspect of the pH-dependence.
AB  - Hyaluronan (HA) hydrolysis catalysed by hyaluronidase (HAase) is strongly
      inhibited when performed at a low ratio of HAase to HA concentrations and at low
      ionic strength. This is because long HA chains can form non-active complexes with
      HAase. Bovine serum albumin (BSA) is able to compete with HAase to form
      electrostatic complexes with HA so freeing HAase which then recovers its
      catalytic activity. This BSA-dependence is characterised by two main domains
      separated by the optimal BSA concentration: below this concentration the HAase
      activity increases when the BSA concentration is increased, above this
      concentration the HAase activity decreases. This occurs provided that HA is
      negatively charged and BSA is positively charged, i.e. in a pH range from 3 to
      5.25. The higher the pH value the higher the optimal BSA concentration. Other
      proteins can also modulate HAase activity. Lysozyme, which has a pI higher than
      that of BSA, is also able to compete with HAase to form electrostatic complexes
      with HA and liberate HAase. This occurs over a wider pH range that extends from 3
      to 9. These results mean that HAase can form complexes with HA and recover its
      enzymatic activity at pH as high as 9, consistent with HAase having either a high
      pI value or positively charged patches on its surface at high pH. Finally, the pH
      dependence of HAase activity, which results from the influence of pH on both the
      intrinsic HAase activity and the formation of complexes between HAase and HA,
      shows a maximum at pH 4 and a significant activity up to pH 9.

PMID- 20043993
TI  - Downregulated expression of the secreted glycoprotein follistatin-like 1 (Fstl1)
      is a robust hallmark of preadipocyte to adipocyte conversion.
AB  - Obesity is a public health crisis in the United States. Targeting preadipocyte to
      adipocyte conversion may be an effective approach to regulate adipose mass. Using
      differential screening we identified Fstl1, a secreted glycoprotein with roles in
      immunomodulation, cell growth, cardioprotection, and vascularization, as a
      "preadipokine". Fstl1 is highly expressed in 3T3-L1 preadipocytes and
      dramatically downregulated early in their differentiation to adipocytes. Northern
      blot analysis of murine tissues reveals white adipose tissue (WAT), lung and
      heart as primary sites of Fstl1 transcript expression. In WAT, Fstl1 transcript
      is restricted to the preadipocyte-containing stromal-vascular cell population.
      Time course studies in multiple adipogenesis models reveal downregulation of
      Fstl1 is a hallmark of white and brown adipocyte conversion. By Western blot, we
      show culture media of 3T3-L1 preadipocytes contains high levels of Fstl1 protein
      that rapidly decline in adipocyte conversion. Moreover, we observe a correlation
      between preadipocyte phenotype and Fstl1 expression in that TNFalpha-mediated de
      differentiation of 3T3-L1 adipocytes is accompanied by re-expression of Fstl1
      transcript and protein. Treatment of 3T3-L1 preadipocytes with a panel of 18
      hormones and other agents revealed the demethylating agent 5-aza-cytidine
      decreases Fstl1 transcript and protein levels by approximately 90%. Furthermore,
      of 10 additional preadipocyte-expressed genes analyzed we find Pref-1, Col1A1,
      Sca-1/Ly6a, Lox and Thbs2, are also downregulated by 5-aza-cytidine. Using
      luciferase reporter constructs containing 791 or 3922 bp of the Fstl1 5' flanking
      region, we determine negative transcriptional regulation by Kruppel-like factor
      15. Together, our data suggest downregulation of Fstl1 expression may be an
      important feature of preadipocyte to adipocyte conversion.

PMID- 20043996
TI  - Plasma 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol concentrations
      are decreased in hind limb unloaded Dahl salt-sensitive female rats.
AB  - Plasma 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentration was shown to
      decrease during bed rest in several studies when baseline plasma 25
      hydroxyvitamin D (25-OHD) concentration was sub-optimal. Dahl salt-sensitive
      female (S) rats, but not Dahl salt-resistant female (R) rats, demonstrated a 50%
      decrease in plasma 1,25-dihydroxycholecalciferol (1,25-(OH)(2)D(3)) concentration
      after 28 days of hind limb unloading (HU, disuse model) during low salt intake
      (0.3%). We tested the vitamin D endocrine system response of female S rats to
      hind limb unloading during high salt intake (2%, twice that of standard rat chow
      to mimic salt intake in the USA). Hind limb unloading resulted in lower plasma 25
      OHD(3) concentrations in S-HU rats than in R-HU rats (P<0.05) and greater urinary
      loss of 25-OHD(3) by S-HU rats than by S rats (P<0.05). Plasma 1,25-(OH)(2)D(3)
      concentration of S-HU rats was half that of S rats, but was unchanged in R-HU
      rats. The association of low plasma 25-OHD concentration with decrease in plasma
      1,25-(OH)(2)D concentration of hind limb unloaded rats and of bed rest
      participants (published studies) suggests that low vitamin D status might be a
      risk factor for decrease in plasma vitamin D hormone concentration during long
      term immobilization or bed rest.

PMID- 20043997
TI  - A single amino acid residue, Ala 105, confers 16alpha-hydroxylase activity to
      human cytochrome P450 17alpha-hydroxylase/17,20 lyase.
AB  - In adrenal steroidogenesis, CYP17 catalyses the 17alpha-hydroxylation of
      pregnenolone and progesterone and the subsequent 17,20-lyase reaction, yielding
      adrenal androgens. The enzyme exhibits distinctly different selectivities towards
      these substrates in various species. CYP17 has also been shown to exhibit 16alpha
      hydroxylase activity towards progesterone in some species, with only human and
      chimp CYP17 catalysing the biosynthesis of substantial amounts of 16
      OHprogesterone. The 16alpha-hydroxylase activity was investigated by introducing
      an Ala105Leu substitution into human CYP17. The converse mutation, Leu105Ala was
      introduced into the baboon, goat and pig enzymes. Wt human CYP17 converted
      approximately 30% progesterone to 16-OHprogesterone while the Ala105Leu mutant
      converted negligible amounts to 16-OHprogesterone ( approximately 9%), comparable
      to wt CYP17 of the other three species when expressed in COS-1 cells. The ratio
      of 17-hydroxylated products to 16-OHprogesterone of human CYP17 was 2.7 and that
      of the mutant human construct 10.5. Similar ratios were observed for human and
      goat CYP17 with the corresponding Ala or Leu residues. Although the Leu105Ala
      mutation of both baboon and pig CYP17 exhibited the same trend regarding the
      ratios, the rate of progesterone conversion was reduced. Coexpression with
      cytochrome b(5) significantly decreased the ratio of 17-hydroxylated products to
      16-OHprogesterone in the Leu105 constructs, while effects were negligible with
      Ala at this position. Homology models show that Ala105 faces towards the active
      pocket in the predicted B'-C domain of CYP17. The smaller residue allows more
      flexibility of movement in the active pocket than Leu, presenting both the C16
      and C17 of progesterone to the iron-oxy complex.

PMID- 20043998
TI  - In vitro characterization of ZK 230211--A type III progesterone receptor
      antagonist with enhanced antiproliferative properties.
AB  - The progesterone receptor (PR) is a key regulator of female reproductive
      functions. Compounds with progesterone inhibiting effects (PR antagonists) have
      found numerous utilities in female reproductive health, ranging from
      contraception to potential treatment of progesterone-dependent diseases like
      uterine leiomyomas. Based on in vitro characteristics such as DNA binding
      activity and partial agonistic transcriptional behavior in the presence of
      protein kinase A activators (cyclic-AMP), three types of PR modulators with
      antagonistic properties have been defined. In this study, we analyzed the in
      vitro characteristics of the PR antagonist ZK 230211 in comparison to the
      classical antagonists onapristone and mifepristone. We focused on PR actions in
      genomic signaling pathways, including DNA binding activity, nuclear localization
      and association with the nuclear receptor corepressor (NCoR) as well as actions
      in non-genomic signaling, such as the activation of c-Src kinase signaling and
      cyclin D1 gene promoter activity. ZK 230211 represents a type of PR antagonist
      with increased inhibitory properties in comparison to mifepristone and
      onapristone. When liganded to the progesterone receptor, ZK 230211 induces a
      strong and persistent binding to its target response element (PRE) and increases
      NCoR recruitment in CV-1 cells. Furthermore, ZK 230211 displays less agonistic
      properties with regard to the association of PR isoform B and the cytoplasmic c
      Src kinase in HeLa cells. It represses T47D cell cycle progression, in particular
      estradiol-induced S phase entry. In summary, our studies demonstrate ZK 230211 to
      be a type III progesterone receptor antagonist which is characterized by very
      strong DNA binding activity and strong antiproliferative effects in the cancer
      cell lines HeLa and T47D.

PMID- 20043999
TI  - Molecular and functional characterization of an acetyl-CoA acetyltransferase from
      the adzuki bean borer moth Ostrinia scapulalis (Lepidoptera: Crambidae).
AB  - Two types of thiolases are involved in the synthesis and catabolism of fatty
      acids; acetyl-CoA acetyltransferase (AT) which catalyzes the formation of
      acetoacetyl-CoA from acetyl-CoA by transferring an acetyl group from one acetyl
      CoA molecule to another, and 3-ketoacyl-CoA thiolase which catalyzes a reversible
      thiolytic cleavage of 3-ketoacyl-CoA into acetyl-CoA and acyl-CoA. Although many
      mammalian thiolases have been characterized in detail, no thiolases from insects
      have been functionally characterized to date. Here we report first
      characterization of an insect AT gene, Osat1, from the pheromone gland of the
      adzuki bean borer moth Ostrinia scapulalis (Lepidoptera; Crambidae). Osat1
      encodes a 41.2 kDa protein comprising 396 amino acid residues (OsAT1), which
      possesses structural features of the thiolase family. An Osat1 homologue of
      Bombyx mori (Bmat1) was cloned through exploration of an EST library of the
      silkworm. Subsequent survey of the genome database revealed that B. mori has at
      least six Osat1 homologues, among which Bmat1 was most closely related to Osat1.
      We expressed recombinant OsAT1 using a baculovirus expression system, and
      verified that OsAT1 catalyzes the formation of acetoacetyl-CoA from acetyl-CoA.
      Osat1 was expressed in all adult tissues examined. These results indicate that
      OsAT1 is a functional AT ubiquitously expressed in O. scapulalis tissues.

PMID- 20044000
TI  - Broadly and narrowly tuned odorant receptors are involved in female sex pheromone
      reception in Ostrinia moths.
AB  - Mate-finding communication in many moths is mediated by sex pheromones produced
      by females. Since the differentiation of sex pheromones is often associated with
      speciation, it is intriguing to elucidate how the changes in sex pheromones are
      tracked by the pheromone recognition system of the males. Moths of the genus
      Ostrinia, which show distinct differentiation in female sex pheromones, are good
      models to study this. The present study was initiated with the aim of identifying
      ORs from Ostrinia scapulalis that respond to its own pheromone components, (E)-11
      and (Z)-11-tetradecenyl acetates. We isolated six OR gene candidates (OscaOR3-8)
      from O. scapulalis. The same set of genes homologous to OscaOR3-8 were conserved
      in all (eight) Ostrinia species examined in addition to the previously reported
      OscaOR1 (tuned to (E)-11-tetradecenol) and the Or83b homologue OscaOR2. OscaOR3
      not only responded to (E)-11- and (Z)-11-tetradecenyl acetates, but also to the
      pheromone components of the congeners, (Z)-9-, (E)-12-, and (Z)-12-tetradecenyl
      acetates. OscaOR4 responded with a relatively high specificity to (E)-11
      tetradecenyl acetate. While OscaOR5 responded only marginally to a few pheromone
      components, OscaOR6-8 did not respond to any of the compounds tested. A few
      conserved ORs, including a unique one with very broad responsiveness, appear to
      be involved in the sex pheromone reception in O. scapulalis. The findings of the
      present study are discussed with reference to knowledge on electrophysiological
      response profiles of olfactory receptor neurons in Ostrinia moths.

PMID- 20044001
TI  - Chronic psychosocial stress triggers cognitive impairment in a novel at-risk
      model of Alzheimer's disease.
AB  - Although it is generally accepted that Abeta contributes to the pathogenesis of
      Alzheimer's disease (AD), other factors that impact the severity and time of
      onset of the disease are not well known. Aside from genetic factors,
      environmental factors such as stress may also play a critical role in the
      manifestation of AD. The present study examined the effect of chronic
      psychosocial stress in an at-risk, subthreshold Abeta (subAbeta) rat model of AD
      by three approaches: learning and memory tests in the radial arm water maze,
      electrophysiological recordings of long-term potentiation (LTP) in anesthetized
      rats, and immunoblot analysis of learning- and memory-related signaling
      molecules. Chronic psychosocial stress was induced using a rat intruder model.
      The subAbeta rat model of AD was induced by continuous i.c.v. infusion of 160
      pmol/day Abeta(1-42) via a 14-day osmotic pump. Behavioral tests and
      electrophysiological recordings showed that subAbeta rats were not significantly
      different from control rats. However, chronically stressed subAbeta rats showed
      more significant impairment of cognitive functions and early-phase LTP (E-LTP)
      than that caused by stress alone. Molecular analysis of essential signaling
      molecules after induction of E-LTP revealed an increase in the levels of p-CaMKII
      in control as well as subAbeta infused rats, but not in stressed or stressed at
      risk rats. In addition, compared to unstimulated control, the levels of both
      total CaMKII and calcineurin were increased in all stimulated animals groups
      after HFS. These findings suggest that the stress-induced alterations may
      accelerate the impairment of cognition and synaptic plasticity in individuals "at
      risk" for AD.

PMID- 20044003
TI  - Apoptosis of peripheral blood lymphocytes in Parkinson patients.
AB  - Neuronal cell death by apoptosis is a mechanism involved in Parkinson's disease
      and indirect signs of apoptosis have been found in brain neurons and blood
      lymphocytes. The present study was aimed to directly assess the presence of
      enhanced apoptosis in lymphocytes from 89 idiopathic Parkinson's disease
      patients, 33 untreated and 56 treated, compared with 33 healthy individuals. The
      study of both spontaneous and activation-induced apoptosis of T-lymphocyte
      subsets by annexin-V binding and flow cytometry showed that Parkinson patients
      increased the expression of Fas in circulating CD4(+) T cells, mainly "naive,"
      that correlated with the decrease of these cells in blood. Spontaneous and
      activation-induced apoptosis of CD4(+) T-cell subsets were also significantly
      increased. Thus, in Parkinson patients, peripheral blood CD4(+) T cells have an
      increased susceptibility to apoptosis with Fas involvement. This fact explains
      the decrease in the number of CD4(+) T-cell subsets observed in Parkinson and
      could be related to the neurodegenerative process.

PMID- 20044004
TI  - From iron oxide nanoparticles towards advanced iron-based inorganic materials
      designed for biomedical applications.
AB  - In the last decade the progress achieved on the synthesis of inorganic
      nanostructures has been accompanied by the parallel exploitation of these systems
      in various fields, among them are biology and medicine. We provide here an
      overview of the iron-based inorganic nanostructured materials that have been
      developed and tested in these fields. We will highlight the major concepts on the
      preparation, physical properties and applications of such nanostructures,
      starting from the most investigated iron oxide nanoparticles. We will describe
      then the new generation of inorganic hybrid nanostructures, which are structures
      that integrate in each nano-object multiple inorganic nanocrystals of different
      materials. In our discussion we will focus on those works that have provided a
      sound proof of concept on the potential of the various systems as diagnostic and
      therapeutic agents.

PMID- 20044002
TI  - HIV-1 neuroimmunity in the era of antiretroviral therapy.
AB  - Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders
      (HAND) can affect up to 50% of infected people during the disease course. While
      antiretroviral therapies have substantively increased the quality of life and
      reduced HIV-1-associated dementia, less severe minor cognitive and motor deficits
      continue. Trafficking of HIV-1 into the central nervous system (CNS), peripheral
      immune activation, dysregulated glial immunity, and diminished homeostatic
      responses are the disease-linked pathobiologic events. Monocyte-macrophage
      passage into the CNS remains an underlying force for disease severity. Monocyte
      phenotypes may change at an early stage of cell maturation and immune activation
      of hematopoietic stem cells. Activated monocytes are pulled into the brain in
      response to chemokines made as a result of glial inflammatory processes, which in
      turn, cause secondary functional deficits in neurons. Current therapeutic
      approaches are focused on adjunctive and brain-penetrating antiretroviral
      therapies. These may attenuate virus-associated neuroinflammatory activities
      thereby decreasing the severity and frequency of HAND.

PMID- 20044006
TI  - Preparation of stable isotope-labeled peripheral cannabinoid receptor CB2 by
      bacterial fermentation.
AB  - We developed a bacterial fermentation protocol for production of a stable isotope
      labeled cannabinoid receptor CB2 for subsequent structural studies of this
      protein by nuclear magnetic resonance spectroscopy. The human peripheral
      cannabinoid receptor was expressed in Escherichia coli as a fusion with maltose
      binding protein and two affinity tags. The fermentation was performed in defined
      media comprised of mineral salts, glucose and (15)N(2)-L-tryptophan to afford
      incorporation of the labeled amino acid into the protein. Medium, growth and
      expression conditions were optimized so that the fermentation process produced
      about 2mg of purified, labeled CB2/L of culture medium. By performing a mass
      spectroscopic characterization of the purified CB2, we determined that one of the
      two (15)N atoms in tryptophan was incorporated into the recombinant protein. NMR
      analysis of (15)N chemical shifts strongly suggests that the (15)N atoms are
      located in Trp-indole rings. Importantly, analysis of the peptides derived from
      the CNBr cleavage of the purified protein confirmed a minimum of 95%
      incorporation of the labeled tryptophan into the CB2 sequence. The labeled CB2,
      purified and reconstituted into liposomes at a protein-to-lipid molar ratio of
      1:500, was functional as confirmed by activation of cognate G proteins in an in
      vitro coupled assay. To our knowledge, this is the first reported production of a
      biologically active, stable isotope-labeled G protein-coupled receptor by
      bacterial fermentation.

PMID- 20044005
TI  - A role for 2-arachidonoylglycerol and endocannabinoid signaling in the locomotor
      response to novelty induced by olfactory bulbectomy.
AB  - Bilateral olfactory bulbectomy (OBX) in rodents produces behavioral and
      neurochemical changes associated clinically with depression and schizophrenia.
      Most notably, OBX induces hyperlocomotion in response to the stress of exposure
      to a novel environment. We examined the role of the endocannabinoid system in
      regulating this locomotor response in OBX and sham-operated rats. In our study,
      OBX-induced hyperactivity was restricted to the first 3 min of the open field
      test, demonstrating the presence of novelty (0-3 min) and habituation (3-30 min)
      phases of the open field locomotor response. Levels of the endocannabinoids 2
      arachidonoylglycerol (2-AG) and anandamide were decreased in the ventral
      striatum, a brain region deafferented by OBX, whereas cannabinoid receptor
      densities were unaltered. In sham-operated rats, 2-AG levels in the ventral
      striatum were negatively correlated with distance traveled during the novelty
      phase. Thus, low levels of 2-AG are reflected in a hyperactive open field
      response. This correlation was not observed in OBX rats. Conversely, 2-AG levels
      in endocannabinoid-compromised OBX rats correlated with distance traveled during
      the habituation phase. In OBX rats, pharmacological blockade of cannabinoid CB(1)
      receptors with either AM251 (1 mg kg(-1) i.p.) or rimonabant (1 mg kg(-1) i.p.)
      increased distance traveled during the habituation phase. Thus, blockade of
      endocannabinoid signaling impairs habituation of the hyperlocomotor response in
      OBX, but not sham-operated, rats. By contrast, in sham-operated rats, effects of
      CB(1) antagonism were restricted to the novelty phase. These findings suggest
      that dysregulation in the endocannabinoid system, and 2-AG in particular, is
      implicated in the hyperactive locomotor response induced by OBX. Our studies
      suggest that drugs that enhance 2-AG signaling, such as 2-AG degradation
      inhibitors, might be useful in human brain disorders modeled by OBX.

PMID- 20044008
TI  - The blind, the lame, and the poor signals of brain function--a comment on Sirotin
      and Das (2009).
AB  - Last year, a study appeared that questioned the generally held assumption of a
      generic coupling between electrical and hemodynamic signs of neural activity
      (Sirotin and Das, 2009). Although the findings of that study can barely surprise
      the specialists in the field, it has caused a considerable confusion in the
      nonspecialist community due to the unwarranted claim of having discovered a
      "hitherto unknown signal." According to this claim, functional magnetic resonance
      imaging (fMRI) would pick up not only signals that reflect electrical brain
      activity but also purely hemodynamic signals that are not linked to neural
      activity. Here, we show that that study's failure to obtain significant
      electrophysiological responses to task structure is easily understood on the
      basis of findings reported for related functional paradigms. Ironically and
      counter its intention, the study by Sirotin and Das reminds us of the exquisite
      sensitivity of spatially pooled hemodynamic signals and the limitations of
      recording only very local samples of electrical activity by microelectrodes. We
      suggest that this sensitivity of hemodynamic signals should be converted into
      spatial resolution. In other words, hemodynamic signals should be used to create
      maps. Further, we suggest that electrical recordings should be obtained at
      systematically varying functional positions across these maps. And we speculate
      that under such appropriate experimental and analytical circumstances
      correspondence between the two modalities would be retrieved-at the expense of a
      novel signal lost in oblivion.

PMID- 20044007
TI  - Perceptual shape sensitivity to upright and inverted faces is reflected in
      neuronal adaptation.
AB  - Using an fMR-adaptation paradigm for different face morphing levels we have
      recently demonstrated a narrow neuronal tuning to faces even at the sub-exemplar
      level which was tightly related to perceptual discrimination (Gilaie-Dotan and
      Malach, 2007). However, it is unclear whether this relationship is unique to
      faces or is a general property of object representations including unfamiliar
      objects, and whether the adaptation tuning is due to physical changes in the
      stimulus or to changes in perceptual discrimination. Here we compared the same
      face-morph paradigm for upright and inverted faces, thus modulating familiarity
      and perceptual discrimination effects while equating all low-level features. We
      found, as expected, a perceptual "inversion effect", i.e. a significant reduction
      in inverted face discrimination. Importantly, the fMR-adaptation tuning in the
      fusiform face area (FFA) changed in accordance with the different perceptual
      sensitivity both for upright and inverted faces. Additional object selective
      regions displayed differential tuning widths to the two categories. Our results
      are compatible with a model by which the ability of human observers to
      discriminate objects depends on the shape tuning properties of individual
      neurons.

PMID- 20044009
TI  - Looking for neuronal currents using MRI: an EEG-fMRI investigation of fast MR
      signal changes time-locked to frequent focal epileptic discharges.
AB  - RATIONALE: Reproducible direct measurement of neuronal electrical activity using
      MRI signal changes due to local magnetic field perturbations would represent a
      step change in neuroimaging methods. While some previous studies using
      experiments based on evoked and spontaneous activity provided encouraging results
      no clear demonstration of neuronal current-related MR changes in the human brain
      has emerged to date. The availability of simultaneously acquired EEG-fMRI in
      patients with frequent interictal epileptic discharges (IED), which have
      significantly greater amplitude than evoked potentials, offers the opportunity to
      further investigate the phenomenon. METHODS: We re-analysed simultaneously
      acquired EEG-fMRI data in 6 epilepsy patients with very frequent focal IED and a
      well-localised generator. A model of MRI signal changes due to fast activity and
      BOLD signal changes was used to identify fast MR signal changes, potentially
      directly reflecting neuronal activity. Simultaneously-acquired EEG allowed the
      comparison of electrical source localisation (ESI), clinical epilepsy
      localisation and BOLD signal changes with the fast MR signal changes. RESULTS:
      Clusters of IED-related fast MR signal change were observed in all cases. Spatial
      correspondence between the IED-related fast MR, BOLD, ESI clusters and irritative
      zone (IZ) was observed in one slice of a single dataset. The other IED-related
      fast MR clusters were remote from electro-clinically determined generators of
      interictal activity. The sign and magnitude of the fast MR signal changes varied
      across regions and subjects. CONCLUSION: The observed fast MR changes cannot be
      confidently attributed to the direct effect of neuronal currents due to lack of
      spatial concordance with generators of interictal activity, IED-related BOLD
      clusters and ESI estimates.

PMID- 20044010
TI  - Troubleshooting PEG-hGH detection supporting pharmacokinetic evaluation in growth
      hormone deficient patients.
AB  - INTRODUCTION: The ability to quantify systemic concentrations of protein
      therapeutics is complicated by the presence of endogenous analyte, specific
      binding proteins, and nonspecific matrix components in biological matrices (Lee &
      Ma, 2007). Further complications can be introduced following pegylation whereby
      polyethylene glycol (PEG) impedes epitope recognition. Due to substantial
      interference from high affinity binding proteins and the inability to measure
      systemic drug concentrations under normal conditions, acid dissociation was
      implemented to facilitate the pharmacokinetic evaluation of clinical samples
      containing pegylated human growth hormone (PEG-hGH). METHODS: A sandwich
      electrochemiluminescent immunosorbent assay (ECLA) was employed using an anti-PEG
      capture, anti-hGH detection format, thereby eliminating cross-reactivity with
      endogenous compound. Samples were acid treated with glycine buffered hydrochloric
      acid (approximately pH 2.0) to dissociate PEG-hGH from serum resident growth
      hormone binding protein (GHBP; 3). After neutralization with a HEPES-based
      neutralizing buffer, samples were diluted in a casein-based assay buffer
      containing 0.2% I-block, 0.1% Tween-20, 2M NaCl, and 10% normal mouse serum to
      eliminate nonspecific matrix effects. Meso Scale Discovery (MSD) technology was
      employed to achieve sensitivity requirements. RESULTS: The drug detection assay
      was validated in the presence and absence of acid dissociation. Validation
      parameters included: intra- and inter-assay accuracy and precision, selectivity
      (>60 lots of normal and growth hormone deficient human serum), cross
      reactivity/specificity (Genotropin, hemoglobin, lipid, and bilirubin), dilutional
      linearity and stability (DeSilva et al., 2003; Shah et al., 1992; Smolec et al.,
      2005 Viswanathan et al., 2007; Food and Drug Administration, 2001). A 10-fold
      molar excess of GHBP was found to decrease PEG-hGH detection by >90% while acid
      dissociation was shown to recover >80% of the analyte. PEG-hGH clinical
      pharmacokinetic samples were analyzed with and without acid treatment. Only 38%
      of the mid-dose samples were quantifiable without acid treatment while 92% were
      quantifiable after acid dissociation. DISCUSSION: The implementation of acid
      dissociation was found to substantially increase the number of quantifiable
      pharmacokinetic samples over the drug exposure time course and contributed
      significantly to the robustness of pharmacokinetic evaluation.

PMID- 20044011
TI  - Bactericidal activity of telavancin, vancomycin and metronidazole against
      Clostridium difficile.
AB  - We compared the time-kill activities of telavancin, vancomycin and metronidazole
      at concentrations of 2 times, 4 times, and 8 times their respective MICs against
      five Clostridium difficile strains including REA type BI, using inocula that
      contained predominantly either vegetative cells or spores. Telavancin MICs (0.125
      0.25 microg/ml) were 2-8-fold lower than those of vancomycin. Telavancin was
      bacteriostatic, reducing the inoculum by 1-2.5 log(10) after 24 h. No major
      differences occurred with the different inoculum forms or the REA types. Although
      telavancin MICs were 2-8 times lower than vancomycin, both demonstrated similar
      bacteriostatic activity against C. difficile while metronidazole was
      bactericidal.

PMID- 20044012
TI  - Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell
      immunoglobulin-like receptors/HLA-ligand mismatched patients following
      hematopoietic cell transplantation.
AB  - The prognosis after hematopoietic cell transplantation (HCT) for the treatment of
      leukemia or lymphoma in humans is influenced by donor-derived natural killer (NK)
      cells, which enhance the graft-versus-leukemia (GVL) effect. Such alloreactive
      killer cells can be generated in vivo after HCT if the donor expresses killer
      cell immunoglobulin-like receptors (KIRs), such as KIR2DL1, KIR2DL2/3, or
      KIR3DL1, for which the recipient lacks HLA class I ligands. We studied effector
      cells from 22 KIR/HLA-ligand mismatched and 14 KIR/HLA-ligand matched, primarily
      HLA-matched patient-donor pairs after allogeneic HCT. A novel 8-color flow
      cytometry panel allowed us to characterize effector-cell populations without
      "broadly reactive" inhibitory receptors such as CD94/NKG2A or LIR1. The numbers
      of such NKG2A(-) LIR1(-) NK cells increased following HCT in patients
      transplanted by KIR/HLA-ligand mismatched grafts, compared to KIR/HLA-ligand
      matched grafts, and in patients transplanted from donors of the A/B, compared to
      A/A, KIR haplotypes. NKG2A(-)LIR1(-) NK cells expressing only those inhibitory
      KIRs for which the patient had no HLA class I ligands could be stimulated by HLA
      class I-deficient cells to express CD107a. Thus, NKG2A(-)LIR1(-) NK cells may be
      important GVL effector cells following HCT, even in patients transplanted from
      HLA-matched donors.

PMID- 20044013
TI  - The dynamic plant chondriome.
AB  - The higher plant chondriome is highly dynamic both in terms of the morphology and
      velocity of individual mitochondria within any given cell. Plant mitochondrial
      dynamics is a relatively new area of research, but one that has developed
      considerably over the early years of this century due to the generation of
      mitochondrially targeted fluorescent protein constructs and stably transformed
      lines. Several putative members of the plant mitochondrial division apparatus
      have been identified, but no genes have been identified as being involved in
      mitochondrial fusion. Despite the highly dynamic nature of plant mitochondria
      there is little specific scientific evidence linking mitochondrial dynamics to
      organelle and cell function. Two exceptions to this are the changes in
      mitochondrial dynamics that are early events during the induction of cell death
      programmes, and the extensive mitochondrial fusion that occurs before
      cytokinesis, although in both cases the role(s) of these events are a matter for
      conjecture.

PMID- 20044014
TI  - ER quality control in the biogenesis of MHC class I molecules.
AB  - Class I molecules of the major histocompatibility complex play a vital role in
      cellular immunity, reporting on the presence of viral or tumor-associated
      antigens by binding peptide fragments of these proteins and presenting them to
      cytotoxic T cells at the cell surface. The folding and assembly of class I
      molecules is assisted by molecular chaperones and folding catalysts that comprise
      the general ER quality control system which also monitors the integrity of the
      process, disposing of misfolded class I molecules through ER associated
      degradation (ERAD). Interwoven with general ER quality control are class I
      specific components such as the peptide transporter TAP and the tapasin-ERp57
      chaperone complex that supply peptides and monitor their loading onto class I
      molecules. This ensures that at the cell surface class I molecules will possess
      mainly optimal peptides with a long half-life. In this review we discuss these
      processes as well as a number of strategies that viruses have evolved to subvert
      normal class I assembly within the ER and thereby evade immune recognition by
      cytotoxic T cells.

PMID- 20044015
TI  - Characterizing the role of the microtubule binding protein Bim1 in Cryptococcus
      neoformans.
AB  - During sexual development the human fungal pathogen Cryptococcus neoformans
      undergoes a developmental transition from yeast-form growth to filamentous
      growth. This transition requires cellular restructuring to form a filamentous
      dikaryon. Dikaryotic growth also requires tightly controlled nuclear migration to
      ensure faithful replication and dissemination of genetic material to spore
      progeny. Although the gross morphological changes that take place during
      dikaryotic growth are largely known, the molecular underpinnings that control
      this process are uncharacterized. Here we identify and characterize a C.
      neoformans homolog of the Saccharomyces cerevisiae BIM1 gene, and establish the
      importance of BIM1 for proper filamentous growth of C. neoformans. Deletion of
      BIM1 leads to truncated sexual development filaments, a severe defect in diploid
      formation, and a block in monokaryotic fruiting. Our findings lead to a model
      consistent with a critical role for BIM1 in both filament integrity and nuclear
      congression that is mediated through the microtubule cytoskeleton.

PMID- 20044017
TI  - Relationships between circulating leucocytes and Leucocytozoon simondi in
      mallard, Anas platyrhynchos, ducklings.
AB  - Leucocytozoon simondi is an apicomplexan blood parasite of waterfowl that
      frequently causes significant mortality, and thus is expected to provoke a
      significant immune response in hosts. Using blood smears collected in consecutive
      weeks from 30 wild-stock mallard, Anas platyrhynchos, ducklings, we tested with
      repeated measures analyses for associations between leucocyte profiles and L.
      simondi infection intensities. With each of the five weeks of leucocyte profiles
      as response variables, we found evidence of fewer circulating heterophils and
      more circulating lymphocytes in the third week of infection associated with more
      intense L. simondi infections from the second week, but no significant
      relationships between leucocytes and the other four weeks of L. simondi
      infection. With each of the five weeks of L. simondi infection intensities as
      response variables, we found no associations with leucocyte profiles.
      Collectively, our results did not reveal tight links between leucocyte profiles
      and parasitism by L. simondi. Our data suggest that L. simondi was relatively
      benign to our wild ducks.

PMID- 20044016
TI  - Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall.
AB  - Nitric oxide (NO) is an important regulator of a variety of biological functions,
      and also has a role in the pathogenesis of cellular injury. It had been generally
      accepted that NO is solely generated in biological tissues by specific nitric
      oxide synthases (NOS) which metabolize arginine to citrulline with the formation
      of NO. However, over the last 15 years, nitrite-mediated NO production has been
      shown to be an important mechanism of NO formation in the heart and
      cardiovascular system. Now numerous studies have demonstrated that nitrite can be
      an important source rather than simply a product of NO in mammalian cells and
      tissues and can be a potential vasodilator drug for cardiovascular diseases.
      There are a variety of mechanisms of nitrite reduction to NO and it is now
      appreciated that this process, while enhanced under hypoxic conditions, also
      occurs under normoxia. Several methods, including electron paramagnetic
      resonance, chemiluminescence NO analyzer, and NO electrode have been utilized to
      measure, quantitate, and image nitrite-mediated NO formation. Results reveal that
      nitrite-dependent NO generation plays critical physiological and pathological
      roles, and is controlled by oxygen tension, pH, reducing substrates and nitrite
      levels. In this manuscript, we review the mechanisms of nitrite-mediated NO
      formation and the effects of oxygen on this process with a focus on how this
      occurs in the heart and vessels.

PMID- 20044018
TI  - Effects of cold-exposure and subsequent recovery on cellular proliferation with
      influence of 20-hydroxyecdysone in a lepidopteran cell line (IAL-PID2).
AB  - In developing insects, the peak level of 20-hydroxyecdysone (20E) initiates a
      decrease in cyclin expression, which subsequently triggers an arrest of cellular
      proliferation and the start of differentiation, finally culminating in the moult.
      We investigated the impact of cold-exposure (4 degrees C) and recovery (26
      degrees C) on the cell cycle activity of the Plodia interpunctella Lepidoptera
      cell line IAL-PID2 and on the expression of B-type cyclin (PcycB), ecdysone
      receptor (B1-isoform; PiEcR-B1), and Hsc70 (PiHsc70) mRNA. Cold-exposure
      significantly reduced expression of these mRNAs, while their levels increased to
      above control values during subsequent recovery at the normal growth temperature.
      When cold-exposed cells were returned to 26 degrees C, cell cycle activity
      restarted, but apoptosis was strongly increased. The presence of 20E appeared to
      increase this apoptotic phenomenon. This result is consistent with the described
      protective role of 20E against a variety of stressors and with the capacity of
      20E to induce cell death in different situations. Here, we illustrate for the
      first time a connection between 20E treatment and Hsc70 expression during cold
      exposure and subsequent recovery in insect cells. Combined with the 20E-induced
      apoptotic response, our results suggest that regulation of Hsc70 expression by
      20E could act in synergy with the control of apoptotic cell death in order to
      optimize the survival of specific cell populations after a period of cold
      exposure.

PMID- 20044019
TI  - The anatomy of the respiratory system in Platysternon megacephalum Gray, 1831
      (Testudines: Cryptodira) and related species, and its phylogenetic implications.
AB  - We discuss the morphology of the respiratory system regarding the phylogenetic
      relation among selected Testudines (Tetrapoda: Amniota). Lung structure and the
      associated coelomic organization are compared in Platysternon megacephalum and in
      representatives of the most-likely closely related taxa Chelydridae and
      Testudinoidea (Emydidae+Testudinidae). P. megacephalum shows horizontal
      intrapulmonary septation in the medial chambers, dividing them into dorsal and
      ventral lobes. This structure is found only in Platysternon and in the Emydidae,
      and is interpreted as a possible synapomorphy for these two taxa. In addition to
      further suggested synapomorphies for Platysternon and the Testudinoidea, we found
      - in contrast to previous reports - a small post-pulmonary septum (PPS) and
      incomplete coelomic compartmentalization in the Chelydridae. Thus, all major taxa
      of Testudines possess a PPS. Since this structure is also present in mammals,
      archosaurs and some lepidosaurs, the plesiomorphy of a coelomic
      compartmentalization by the PPS in amniotes in general should be considered.
      These preliminary results indicate that further comparative study of the
      respiratory apparatus might help resolve the phylogenetic relationships among the
      Testudines, as well as to shed light on its evolution among the Amniota.

PMID- 20044020
TI  - Metal accumulation and metallothionein induction in the spotted dogfish
      Scyliorhinus canicula.
AB  - Recent studies indicate that elasmobranch fish respond differently to metal
      exposure than marine teleosts. Accumulation rates can be high, which despite the
      fact that normal background levels for metals in the marine environment are low,
      is worrying due to the long life span and late fecundity of most shark. The goals
      of the present study were to examine differences in accumulation rates and
      toxicity of a range of metals at equimolar concentrations (10microM) in the
      Mediterranean or spotted dogfish, Scyliorhinus canicula. For this purpose, we
      exposed the dogfish to Ni (587microg/L), Cd (1124microg/L), Pb (2072microg/L), Cu
      (635microg/L), and Ag (1079microg/L and two additional exposures at 10microg/L
      and 1microg/L) for one week and measured total metal accumulation,
      metallothionein induction, and parameters related to osmoregulation. Our study
      confirms the high toxicity and accumulation rates of Ag for elasmobranch fish,
      even at levels 100 to 1000 times lower than exposure levels of other metals. Also
      Pb accumulated readily in all organs, but did not cause any osmoregulatory
      disturbance at the exposure levels used. Ni and Cd seem to accumulate primarily
      in the kidney while Cu mainly accumulated in liver. In contrast to Ni and Cd, the
      three other metals Ag, Cu and Pb accumulated in the rectal gland, an important
      organ for osmoregulation and possible target organ for metal toxicity. Only Cu
      succeeded in initiating a protective response by inducing MT synthesis in liver
      and gills.

PMID- 20044021
TI  - Molecular cloning and characterization of prohormone convertase 1 gene in abalone
      (Haliotis diversicolor supertexta).
AB  - Prohormone convertases (PCs) are calcium-dependent serine endoproteases of the
      subtilisin family that play a key role in the posttranslational processing of
      precursors for bioactive peptides. In this study, the cDNA of PC1 from abalone
      (Haliotis diversicolor supertexta) was cloned and sequenced. The PC1 cDNA
      consisted of 2216 bp with an open reading frame of 2010 bp encoding a 670 amino
      acid peptide. Comparative structural analysis revealed that abalone PC1 shared
      high similarity and identity with most PC counterparts. The profile of deduced
      peptide of PC1 was composed of an N-terminal signal peptide, a prosegment domain,
      a catalytic domain and a P domain, which were common in many species. Sequence
      analysis indicated that the abalone PC1 was highly conserved in catalytic domain,
      including three conserved serine catalytic signatures that comprised a catalytic
      triad active center. Also conserved were the potential cleavage site for release
      of the mature peptide, a cognate integrin binding site RGD in P domain, and four
      cysteine residues involved in forming an intrachain disulfide bridge. To further
      investigate the functions of PC1 in abalone, real-time quantitative PCR was
      performed to determine the expression level of this gene at three different
      reproduction stages (i.e. pre-, during- and post-breeding). Results indicated
      that PC1 was expressed throughout the three stages but the expression levels
      varied with the timepoints and different tissues in abalone. The expression
      levels of PC1 in digestive gland were much higher than those of the gonad. In
      female abalone, the expression of PC1 was higher at pre-breeding and during
      breeding stages (P<0.05), and the expression declined at the subsequent stage.
      Whereas, the level of PC1 in male individual did not exhibit a significant
      difference in various reproduction stages. Also, the natural enzyme activity of
      PC1 partially exhibited a similar tendency with the mRNA expression. According to
      the results, it can be concluded that PC1 gene is involved in the abalone
      reproduction process (e.g. spawning or sperming). PC1 is a potential prohormone
      processing enzyme and it may play a critical role in abalone physiological
      processes related to reproduction.

PMID- 20044022
TI  - Effect of plant-based feed ingredients on osmoregulation in the Atlantic salmon
      lens.
AB  - Lenses of adult Atlantic salmon fed with a plant oil and plant protein-based diet
      (plant diet) were compared to lenses of fish fed a diet based on traditional
      marine ingredients (marine diet) with respect to biochemical composition and
      functionality ex vivo. After 12 months of feeding, plant diet-fed fish had
      smaller lenses with higher water contents and lower concentrations of histidine
      (His) and N-acetylhistidine (NAH) than fish fed with the marine diet. Cataract
      development in both dietary groups was minimal and no differences between the
      groups were observed. Lens fatty acid and lipid class composition differed
      minimally, although a significant increase in linoleic acid was observed. The
      lenses were examined for their ability to withstand osmotic disturbances ex vivo.
      Culture in hypoosmotic and hyperosmotic media led to increase and decrease of
      lens volume, respectively. Lenses from plant diet-fed fish were less resistant to
      swelling and shrinking, released less NAH into the culture medium, and
      accumulated His and NAH at higher rates than lenses from marine diet-fed fish.
      Culture in hypoosmotic medium resulted in higher cataract scores than in control
      and hyperosmotic medium. mRNA expression of selected genes, including glutathione
      peroxidase 4 and SPARC (secreted protein acidic and rich in cysteine), was
      affected by diet and osmotic treatment. It can be concluded that lenses of farmed
      Atlantic salmon are affected by the diet composition, both in biochemical
      composition and physiological functionality in relation to osmoregulation.

PMID- 20044023
TI  - Oxidized phosphatidylcholine stimulates activity of secretory phospholipase A2
      group IIA and abolishes sphingomyelin-induced inhibition of the enzyme.
AB  - We have shown recently that oxidized but not native lipoproteins stimulate the
      activity of secretory phospholipase A2 group IIA (sPLA(2)(IIA)). Since oxidized
      lipoproteins potentially contain considerable amounts of oxidized
      phosphatidylcholine, we examined the effect of oxidized palmitoyl arachidonyl
      phosphatidylcholine (oxPC) and the competitive effects of oxPC and sphingomyelin
      (SM) on sPLA(2)(IIA) activity. OxPC either added to the assay medium as separated
      liposomes or incorporated in varied amounts into LDL progressively enhanced the
      activity of purified human sPLA(2)(IIA) and abolished the inhibitory effect of
      LDL-incorporated SM on the enzyme activity. OxPC completely abolished the
      inhibitory effect of SM at the oxPC/SM concentration ratio 1/2. On the other
      hand, SM suppressed the activating effect of oxPC in a dose-dependent manner,
      abolishing it almost completely at a concentration 8 times as high as that of
      oxPC. Thus, changes in the oxPC/SM concentration ratio in LDL may affect the
      regulatory mechanisms of sPLA(2)(IIA) activity in human blood, inducing
      stimulation or inhibition of the enzyme. Influence on regulation of sPLA(2)(IIA)
      activity can be useful in the development of new therapeutic approaches to the
      treatment of cardiovascular diseases.

PMID- 20044024
TI  - Prostaglandin A2 activates intrinsic apoptotic pathway by direct interaction with
      mitochondria in HL-60 cells.
AB  - HL-60 cells treated by prostaglandin (PG) A(2) showed characteristics of
      apoptosis such as accumulation of hypodiploid and annexin V positive cells,
      condensed and fragmented nuclei, cytochrome c (Cyt C) release from mitochondria
      and activation of caspase-1, -2, -3, -7 and -9. PGA(2)-induced cell death was
      rescued by inhibitors of caspase-9 and -3, but PGA(2)-induced Cyt C release was
      not prevented by caspase inhibitors. During Cyt C release by PGA(2),
      mitochondrial transmembrane potential was maintained and mitochondrial
      permeability transition pore was not formed. In addition, anti-apoptotic BCL-2
      family proteins like BCL-2 and BCL-XL, and ROS scavengers including ascorbic acid
      and 2,2,6,6-tetramethyl-1-piperidinyloxy were not able to inhibit Cyt C release
      as well as apoptosis by PGA(2). Finally, it was shown that PGA(2)-induced Cyt C
      release in vitro from purified mitochondria in the absence of cytosolic
      components. Furthermore, thiol-containing compounds such as N-acetylcysteine, l
      cysteine and monothioglycerol prevented Cyt C release, and hence induction of
      apoptosis. Taken together, these results suggest that PGA(2) activates intrinsic
      apoptotic pathway by directly stimulating mitochondrial outer membrane
      permeabilization to release Cyt C, in which thiol-reactivity of PGA(2) plays a
      pivotal role.

PMID- 20044025
TI  - Annexin A6-regulator of the EGFR/Ras signalling pathway and cholesterol
      homeostasis.
AB  - Annexin A6 (AnxA6) belongs to the highly conserved annexin protein family. Like
      other annexins, the function of AnxA6 is linked to its ability to bind
      phospholipids in a Ca(2+)-dependent manner, thereby interacting with cellular
      membranes in a dynamic, reversible and regulated fashion. Upon cell activation,
      AnxA6 is recruited to the plasma membrane, endosomes and caveolae/membrane rafts
      to interact with signalling proteins, the endocytic machinery and actin
      cytoskeleton to inhibit epidermal growth factor receptor and Ras signalling. In
      addition, AnxA6 associates with late endosomes to regulate cholesterol export
      leading to reduced cytoplasmic phospholipase A2 activity and caveolae formation.
      Accordingly, AnxA6 may function as an organizer of membrane domains (i) to create
      a scaffold for the formation of multifactorial signalling complexes, (ii) to
      regulate transient membrane-actin interactions during endocytic transport, and
      (iii) to modulate intracellular cholesterol homeostasis. Altogether, this will
      regulate critical physiological processes including proliferation,
      differentiation, inflammation and cell migration.

PMID- 20044026
TI  - Adiponectin--it's all about the modifications.
AB  - Adiponectin is an adipokine (adipocyte-derived hormone) with multiple salutary
      effects. It is secreted into the circulation as low molecular weight (LMW) and
      high molecular weight (HMW) multimers with the latter being more metabolically
      active. Extensive post-translational modifications (PTMs) are required for
      efficient adiponectin multimerisation and secretion. Recent studies have
      identified novel PTMs that contribute to the efficacy of adiponectin production
      and clearance. Thiol-mediated retention of adiponectin occurs during transit
      through the ER, via direct interactions with chaperones including ERp44 and DsbA
      L, and facilitates multimerisation and secretion. Interestingly, this appears to
      be in direct competition with adiponectin succination. Adiponectin is also
      subject to O-glycosylation/sialylation which affects clearance from the
      circulation. In contrast to most adipokines, reduced adiponectin levels,
      particularly HMW, contribute to the aetiology of obesity-related diseases such as
      type 2 diabetes and cardiovascular disease. Strategies that modulate processes
      governing PTM of adiponectin represent attractive therapeutic approaches.

PMID- 20044027
TI  - Phosphatidylethanolamine synthesized by four different pathways is supplied to
      the plasma membrane of the yeast Saccharomyces cerevisiae.
AB  - In this study, we examined the contribution of the four different pathways of
      phosphatidylethanolamine (PE) synthesis in the yeast Saccharomyces cerevisiae to
      the supply of this phospholipid to the plasma membrane. These pathways of PE
      formation are decarboxylation of phosphatidylserine (PS) by (i)
      phosphatidylserine decarboxylase 1 (Psd1p) in mitochondria and (ii)
      phosphatidylserine decarboxylase 2 (Psd2p) in a Golgi/vacuolar compartment, (iii)
      incorporation of exogenous ethanolamine and ethanolamine phosphate derived from
      sphingolipid catabolism via the CDP-ethanolamine pathway in the endoplasmic
      reticulum (ER), and (iv) synthesis of PE through acylation of lyso-PE catalyzed
      by the acyl-CoA-dependent acyltransferase Ale1p in the mitochondria associated
      endoplasmic reticulum membrane (MAM). Deletion of PSD1 and/or PSD2 led to
      depletion of total cellular and plasma membrane PE level, whereas mutation in the
      other pathways had practically no effect. Analysis of wild type and mutants,
      however, revealed that all four routes of PE synthesis contributed not only to PE
      formation but also to the supply of PE to the plasma membrane. Pulse-chase
      labeling experiments with L[(3)H(G)]serine and [(14)C]ethanolamine confirmed the
      latter finding. Fatty acid profiling demonstrated a rather balanced incorporation
      of PE species into the plasma membrane irrespective of mutations suggesting that
      all four pathways of PE synthesis provide at least a basic portion of "correct"
      PE species required for plasma membrane biogenesis. In summary, the PE level in
      the plasma membrane is strongly influenced by total cellular PE synthesis, but
      fine tuned by selective assembly mechanisms.

PMID- 20044029
TI  - Hyperforin induces Ca(2+)-independent arachidonic acid release in human platelets
      by facilitating cytosolic phospholipase A(2) activation through select
      phospholipid interactions.
AB  - Here, we investigated the modulation of cytosolic phospholipase A(2) (cPLA(2))
      mediated arachidonic acid (AA) release by the polyprenylated acylphloroglucinol
      hyperforin. Hyperforin increased AA release from human platelets up to 2.6 fold
      (maximal effect at 10microM) versus unstimulated cells, which was blocked by
      cPLA(2)alpha-inhibition, and induced translocation of cPLA(2) to a membrane
      compartment. Interestingly, these stimulatory effects of hyperforin were even
      more pronounced after depletion of intracellular Ca(2+) by EDTA plus BAPTA/AM.
      Hyperforin induced phosphorylation of cPLA(2) at Ser505 and activated p38 mitogen
      activated protein kinase (MAPK), and inhibition of p38 MAPK by SB203580 prevented
      cPLA(2) phosphorylation. However, neither AA release nor translocation of cPLA(2)
      was abrogated by SB203580. In cell-free assays using liposomes prepared from
      different lipids, hyperforin failed to stimulate phospholipid hydrolysis by
      isolated cPLA(2) in the presence of Ca(2+). However, when Ca(2+) was omitted,
      hyperforin caused a prominent increase in cPLA(2) activity using liposomes
      composed of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphoethanolamine but not of
      1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine (PAPC) unless the PAPC
      liposomes were enriched in cholesterol (20 to 50%). Finally, two-dimensional (1)H
      MAS-NMR analysis visualized the directed insertion of hyperforin into POPC
      liposomes. Together, hyperforin, through insertion into phospholipids, may
      facilitate cPLA(2) activation by enabling its access towards select lipid
      membranes independent of Ca(2+) ions. Such Ca(2+)- and phosphorylation
      independent mechanism of cPLA(2) activation may apply also to other membrane
      interfering molecules.

PMID- 20044028
TI  - alpha(1)-fetoprotein transcription factor (FTF)/liver receptor homolog-1 (LRH-1)
      is an essential lipogenic regulator.
AB  - alpha(1)-Fetoprotein transcription factor (FTF), also known as liver receptor
      homolog 1 (LRH-1) is highly expressed in the liver and intestine, where it is
      implicated in the regulation of cholesterol, bile acid and steroid hormone
      homeostasis. FTF is an important regulator of bile acid metabolism. We show here
      that FTF plays a key regulatory role in lipid homeostasis including triglyceride
      and cholesterol homeostasis. FTF deficient mice developed lower levels of serum
      triglyceride and cholesterol as a result of lower expression of several hepatic
      FTF target genes. Chenodeoxycholic acid repressed FTF expression resulting in a
      decrease in serum triglyceride in wild-type mice. The absence of chenodeoxycholic
      acid-mediated repression in FTF(+/-) mice demonstrated the essential role of FTF
      in triglyceride metabolism. Taken together, our results identify the nuclear
      receptor FTF as a central regulator of lipid metabolism.

PMID- 20044030
TI  - Primary structures of skin antimicrobial peptides indicate a close, but not
      conspecific, phylogenetic relationship between the leopard frogs Lithobates onca
      and Lithobates yavapaiensis (Ranidae).
AB  - The phylogenetic relationship between the relict leopard frog Lithobates (Rana)
      onca (Cope, 1875) and the lowland leopard frog Lithobates (Rana) yavapaiensis
      (Platz and Frost, 1984) is unclear. Chromatographic analysis of norepinephrine
      stimulated skin secretions from L. onca led to the identification of six peptides
      with antimicrobial activity. Determination of their primary structures indicated
      that four of the peptides were identical to brevinin-1Ya, brevinin-1Yb, brevinin
      1Yc and ranatuerin-2Ya previously isolated from skin secretions of L.
      yavapaiensis. However, a peptide belonging to the temporin family (temporin-ONa:
      FLPTFGKILSGLF.NH(2)) and an atypical member of the ranatuerin-2 family containing
      a C-terminal cyclic heptapeptide domain (ranatuerin-2ONa:
      GLMDTVKNAAKNLAGQMLDKLKCKITGSC) were isolated from the L. onca secretions but were
      not present in the L. yavapaiensis secretions. Ranatuerin-2ONa inhibited the
      growth of Escherichia coli (MIC=50muM) and Candida albicans (MIC=100muM ) and
      showed hemolytic activity (LC(50)=90muM) but was inactive against Staphylococcus
      aureus. The data indicate a close phylogenetic relationship between L. onca and
      L. yavapaiensis but suggest that they are not conspecific species.

PMID- 20044031
TI  - Metallothionein and superoxide dismutase responses to sublethal cadmium exposure
      in the clam Mactra veneriformis.
AB  - The objective of this study was to identify the relationship between cadmium (Cd)
      and stress responses in the clam Mactra veneriformis. Metallothionein (MT) and Cu
      Zn superoxide dismutase (SOD) cDNAs from the clam were isolated and
      characterized. The full-length cDNA of MvMT and MvSOD contained 830 and 689
      nucleotides encoding 59 and 159 amino acids, respectively. Multiple alignments
      indicated that deduced amino acid sequences of MvMT and MvSOD shared high
      homology with MT and SOD sequences of other mollusks. Clams were exposed to 0,
      50, 100, and 200microg/L Cd for 21days. The mRNA transcripts of the two genes, MT
      protein content and SOD activity in the digestive gland were examined. Cd
      treatment significantly elevated MvMT and MvSOD mRNA expression in a dose
      dependent manner and MT protein level in a dose- and time-dependent manner. SOD
      activity significantly increased at the start of Cd exposure, then decreased and
      finally returned to the normal level. These results indicate that MT and SOD play
      an important role in maintaining cellular metabolism homeostasis and protecting
      M. veneriformis from Cd toxicity. MT and SOD could be used as biomarkers of Cd
      pollution in aquatic environment for the studied species.

PMID- 20044032
TI  - Detection sensitivity of lymph nodes of various sizes using USPIO nanoparticles
      in magnetic resonance imaging.
AB  - Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles-based magnetic
      resonance imaging (MRI) have offered new promise for early detection of lymph
      nodes and their metastases. These nanoparticles are taken up by macrophages in
      normal lymph nodes and produce signal changes based on susceptibility artifact
      and dipolar relaxation. The effects of MR protocols and their parameters on
      artifact size and detection sensitivity have been studied before. In this study
      USPIO nanoparticles were used as MRI contrast agent, and their detection
      sensitivity in axillary lymph nodes was evaluated using earlier defined pulse
      sequences. The minimum amount (dose) of USPIO nanoparticles that delineates lymph
      nodes of various sizes using susceptibility-based gradient echo pulse sequences
      was also determined. It was found that a dose administration of as low as 0.028
      mg iron (Fe)/kg for subcutaneous injection and 0.16 mg Fe/kg for intravenous
      injection can be used to visualize axillary lymph nodes when a sensitive MR
      protocol is employed. FROM THE CLINICAL EDITOR: Ultrasmall superparamagnetic iron
      oxide (USPIO) nanoparticles are taken up by macrophages and have been shown to be
      promising negative contrast agents in the early detection of metastases in lymph
      nodes. In this study, their detection sensitivity in axillary lymph nodes was
      evaluated using previously defined MRI pulse sequences. The minimum dose of USPIO
      to delineate lymph nodes using gradient echo-based optimized pulse sequences was
      0.028 mgFe/kg for subcutaneous and 0.16 mgFe/kg for intravenous injection.

PMID- 20044033
TI  - Dendrosome-based delivery of siRNA against E6 and E7 oncogenes in cervical
      cancer.
AB  - Although small interfering RNA (siRNA) treatment holds great promise for the
      treatment of cancers, the field has been held back by the availability of
      suitable delivery vehicles. For cervical cancer the E6 and E7 oncogenes are ideal
      siRNA targets for treatment. The purpose of the present study was to explore the
      potential of dendrosomes for the delivery of siRNA targeting E6 and E7 proteins
      of cervical cancer cells in vitro. Optimization of dendrimer generation and
      nitrogen-to-phosphate (N/P) ratio was carried out using dendrimer-fluorescein
      isothiocyanate oligo complexes. The optimized N/P ratios were used in formulating
      complexes between dendrimers and siRNA targeting green fluorescence protein
      (siGFP). Although formulation 4D100 (dendrimer-siRNA complex) displayed the
      highest GFP knockdown, it was also found to be highly toxic to cells. In the
      final formulation 4D100 was encapsulated into dendrosomes so as to mask these
      toxic effects. The optimized dendrosomal formulation (DF), DF3 was found to
      possess a siGFP-entrapment efficiency of 49.76% +/- 1.62%, vesicle size of 154 +/
      1.73 nm, and zeta potential of +3.21 +/- 0.07 mV. The GFP knockdown efficiency
      of DF3 (dendrosome) was found to be almost identical to that of 4D100, but the
      former was completely nontoxic to the cells. DF3 containing siRNA against E6 and
      E7 was found to knock down the target genes considerably, as compared with the
      other formulations tested. Our results imply that dendrosomes hold potential for
      the delivery of siRNA and that a suitable targeting strategy could be useful for
      applications in vivo. FROM THE CLINICAL EDITOR: siRNA treatment holds great
      promise for the treatment of cancers, but overall, the availability of suitable
      delivery vehicles remains a major issue. The purpose of this study was to explore
      the potential of dendrosomes for the delivery of siRNA targeting specific
      proteins in cervical cancer cells in vitro. The results suggest that dendrosomes
      hold potential for the delivery of siRNA and a suitable targeting strategy could
      be useful for applications in vivo.

PMID- 20044034
TI  - Release dynamics of ciprofloxacin from swellable nanocarriers of poly(2
      hydroxyethyl methacrylate): an in vitro study.
AB  - Swellable polymeric nanosystems have emerged as promising materials in drug
      release technologies. Such systems have shown potential in releasing antibiotic
      drugs and to do so controllably. In the present investigation poly(2-hydroxyethyl
      methacrylate) nanoparticles were synthesized by suspension polymerization of 2
      hydroxyethyl methacrylate and characterized by various techniques such as Fourier
      transform-infrared spectrometry, scanning electron microscopy, particle size
      analysis, and surface charge measurements. The synthesized nanoparticles were
      swellable in water and showed promise to function as a swelling controlled
      release system. The release kinetics of drug-loaded particles was studied in
      phosphate-buffered saline (PBS) using ciprofloxacin as a model antibacterial
      drug. The chemical stability of the pure and released drug was also assessed in
      PBS (pH 7.4), acidic (pH 1.8), and alkaline (pH 8.6) solutions. The in vitro
      blood compatibility of nanoparticles was also investigated in terms of hemolysis
      tests. The drug-loaded nanoparticles were also examined for their antibacterial
      and blood-compatible behaviors. FROM THE CLINICAL EDITOR: Swellable polymeric
      nanosystems have emerged as promising materials in drug release technologies. In
      this paper, the release kinetics, antimicrobial properties and in vitro "blood
      compatibility" is reported for a specific swellable polymeric nanosystem.

PMID- 20044035
TI  - Singlet oxygen-induced apoptosis of cancer cells using upconversion fluorescent
      nanoparticles as a carrier of photosensitizer.
AB  - The photodynamic effect of upconversion nanoparticles loaded with a
      photosensitizer was studied on murine bladder cancer cells (MB49). Mesoporous
      silica was coated onto sodium yttrium fluoride upconversion nanocrystals to form
      a core-shell structure and then loaded with the photosensitizer zinc (II)
      phthalocyanine into the porous silica. The nanoparticles displayed a uniform
      spherical shape with an average diameter of about 50 nm and showed good
      dispersibility in water. Intracellular uptake study in MB49 cells revealed a time
      and concentration-dependent accumulation of these nanoparticles. Upon
      irradiation with 980-nm near-infrared light, their efficiency in activating the
      loaded zinc (II)-phthalocyanine to generate singlet oxygen molecules was
      confirmed in live cells. The cytotoxic effect of the released singlet oxygen from
      the nanoplatform was proven by cell viability assay, confocal microscopy, DNA
      agarose gel electrophoresis, cytochrome c-releasing assay, and prostate-specific
      antigen-enzyme-linked immunosorbent assay, all of which showed a strong
      photodynamic effect of the nanoparticles on MB49 cells. This suggests the
      efficacy of sodium yttrium fluoride upconversion nanoparticles as a carrier for
      photosensitizers and their use in photodynamic therapy of cancer and some other
      diseases. FROM THE CLINICAL EDITOR: In this study, the photodynamic effect of
      upconversion nanoparticles loaded with a photosensitizer was investigated on
      murine bladder cancer cells, with strongly positive results, which may pave its
      way to future clinical use in malignant tumors and potentially other diseases.

PMID- 20044036
TI  - FGFR3 expression in Xenopus laevis.
AB  - We studied the expression of FGF receptor 3 (FGFR3) mRNA throughout early
      development of Xenopus laevis by RT-PCR and in situ hybridization. RT-PCR shows
      that FGFR3 mRNA is localized within the gastrula; regionalized staining is
      detected by the neural plate stage and continues throughout embryonic
      development. Strong expression is seen in developing neural structures,
      especially in the forebrain and hindbrain, including the developing eyes, and in
      lateral mesoderm. Comparison of these data with previous reports of FGF
      expression in this species suggests possible FGF-FGFR3 interactions. The pattern
      of FGFR3 expression appears to be strongly conserved among vertebrate embryos.

PMID- 20044037
TI  - RHAMM mRNA expression in proliferating and migrating cells of the developing
      central nervous system.
AB  - Extracellular matrix components can influence cell behaviour by modulating a wide
      variety of events. In particular, the glycosaminoglycan hyaluronan is involved in
      many processes of the normal and pathological adult cells and it is essential for
      embryonic development. Two main HA receptors have been characterized in
      vertebrate developing embryos: CD44 and RHAMM. These receptors display completely
      different characteristics apart from their ability to bind hyaluronan. RHAMM is
      still the most mysterious hyaluronan receptor as it can act as cell surface
      receptor but it can also be localized in the cytoplasm or in the cell nucleus,
      displaying both hyaluronan dependent and independent functions. In particular,
      the role of RHAMM during embryogenesis is still largely unclear. We reported a
      detailed gene expression analysis of RHAMM during Xenopus laevis development
      comparing its mRNA distribution with that of the hyaluronan synthases and CD44
      genes, in order to provide a first insight into the possible role of RHAMM during
      vertebrate embryogenesis. Our findings point out that RHAMM mRNA displays a
      specific distribution in proliferating regions of the developing neural tube and
      retina where synthesis of hyaluronan is not detected. On the contrary, RHAMM
      expression correlates with the expression of hyaluronan synthase-1 and hyaluronan
      receptor CD44 gene expression in migrating cranial neural crest. These results
      suggest that during the central nervous system development RHAMM could be
      involved in cell proliferation and migration processes both in a hyaluronan
      independent and dependent manner.

PMID- 20044038
TI  - Nestin expression in glial and neuronal progenitors of the developing human
      spinal ganglia.
AB  - Expression of the neural crest marker nestin was studied in glial and neuronal
      progenitors of developing human spinal ganglia using immunohistochemistry in 10
      conceptuses, 5-10 weeks old. Quantification was performed by counting the ratio
      of positive cells in the total cell number, expressed as mean + or - SD and by
      the Mann-Whitney test. Strong expression of nestin in the 5th-6th developmental
      week (56%) decreased to 49% in the foetal period. During the same period, number
      of PGP9.5-positive cells increased from 38% to 42%. At earliest stages, the
      number of cells expressing GFAP was two folds higher (21%) than S100 (11%).
      During further development, their number nearly levelled (23% and 28%,
      respectively), and finally reached level of 25% for GFAP and 40% for S100. While
      expression of nestin was constantly higher in the dorsal parts of spinal ganglia,
      number of PGP9.5-, GFAP- and S100-positive cells was higher in their ventral
      parts, thus indicating ventral to dorsal direction of spinal ganglia
      differentiation. Co-localization of nestin and GFAP or nestin and S100 was
      observed during the whole investigate period, while PGP9.5 did not co-localize
      with nestin. Some ganglion cells simultaneously co-expressing GFAP and S100 might
      be satellite cells and immature Schwann cells. We suggest that some nestin
      positive cells might be capable to differentiate into neurons during the earliest
      stages of development. Gangliogenesis seems to be important process during the
      whole ganglion development. Continuous presence of neural crest cells during
      development might be important in regenerative processes following damage of the
      spinal ganglia.

PMID- 20044039
TI  - The molecular and clinical rationale of extracorporeal photochemotherapy in
      autoimmune diseases, malignancies and transplantation.
AB  - Extracorporeal photochemotherapy, or photopheresis is a low-risk therapeutical
      intervention, which has been introduced in a variety of hematological
      malignancies, autoimmune conditions and transplantation. The mode of action of
      photopheresis encompasses apoptosis-induction and modifications of
      immunoregulatory processes, leading to the elimination of malignant cells, as
      well as the down-modulation of harmful immune responses. Although the beneficial
      effects of the therapy have been depicted in numerous studies, little is known
      about the exact benefits and the molecular mechanisms behind. The aim of the
      present review was to portray some aspects of the molecular and clinical
      rationale of extracorporeal photochemotherapy in autoimmune diseases,
      malignancies and transplantation, and to provide an overview of the treatment in
      the modern clinical management of these diseases.

PMID- 20044040
TI  - Switching TNF-alpha antagonists in rheumatoid arthritis: the experience of the
      LORHEN registry.
AB  - New biologic agents have changed the paradigm of rheumatoid arthritis treatment,
      leading to improvement in managing patients' refractory to classical DMARDs. Anti
      TNF-alpha is used as first-line treatment in patients failing to respond to
      classical DMARDs. However, up to 50% of patients fail to respond to these drugs
      or develop adverse events leading to treatment discontinuation: in these cases
      the optimal treatment strategy is still a matter of debate even if trying with a
      second anti-TNF-alpha is considered a good option. We report data of patients
      switching from a first to a second anti-TNF-alpha from an Italian registry of
      patients with rheumatoid arthritis, showing that switching is valuable in
      patients stopping a first anti-TNFalpha drug. The patients with higher disease
      activity levels and those stopping the first anti-TNFalpha treatment because of a
      lack of efficacy are very likely to respond to the second treatment.

PMID- 20044041
TI  - Rescue of F508del-CFTR by RXR motif inactivation triggers proteome modulation
      associated with the unfolded protein response.
AB  - F508del-CFTR, the most common mutation of the cystic fibrosis transmembrane
      conductance regulator (CFTR) protein, disrupts intracellular trafficking leading
      to cystic fibrosis (CF). The trafficking defect of F508del-CFTR can be rescued by
      simultaneous inactivation of its four RXR motifs (4RK). Proteins involved in the
      F508del-CFTR trafficking defect and/or rescue are therefore potential CF
      therapeutic targets. We sought to identify these proteins by investigating
      differential proteome modulation in BHK cells over-expressing wt-CFTR, F508del
      CFTR or the revertant F508del/4RK-CFTR. By 2-dimensional electrophoresis-based
      proteomics and western blot approaches we demonstrated that over-expression of
      F508del/4RK-CFTR modulates the expression of a large number of proteins, many of
      which are reported interactors of CFTR and/or 14-3-3 with potential roles in CFTR
      trafficking. GRP78/BiP, a marker of ER stress and unfolded protein response
      (UPR), is up-regulated in cells over-expressing either F508del-CFTR or
      F598del/4RK-CFTR. However, over-expression of F508del/4RK-CFTR induces the up
      regulation of many other UPR-associated proteins (e.g. GRP94, PDI,
      GRP75/mortalin) and, interestingly, the down-regulation of proteasome components
      associated with CFTR degradation, such as the proteasome activator PA28 (PSME2)
      and COP9 signalosome (COPS5/CSN5). Moreover, the F508del-CFTR-induced
      proteostasis imbalance, which involves some heat shock chaperones (e.g.
      HSP72/Hpa2), ER-EF-hand Ca(2+)-binding proteins (calumenin) and the proteasome
      activator PA28 (PSME2), tends to be 'restored', i.e., in BHK cells over
      expressing F508del/4RK-CFTR those proteins tend to have expression levels similar
      to the wild-type ones. These findings indicate that a particular cellular
      environment orchestrated by the UPR contributes to and/or is compatible with
      F508del/4RK-CFTR rescue.

PMID- 20044042
TI  - Inhibitors of protein kinases.

PMID- 20044043
TI  - Craniosynostosis: A rare complication of pycnodysostosis.
AB  - Uncommon features of rare genetic disorders are often poorly known, as the
      likelihood of having them reported is low. We describe a 7-year-old boy with
      clinical and radiological diagnosis of pycnodysostosis, and c.436G>C (p.G146R)
      mutation in CSTK). He developed intracranial hypertension that required surgical
      decompression. Despite patent fontanels, the cause of the intracranial
      hypertension was identified to be a combination of coronal and metopic
      craniosynostoses. Intracranial hypertension and craniosynostosis have only been
      reported once in pycnodysostosis, which is on the contrary characterized by
      delayed closure of the sutures and persistence of open fontanels. Our observation
      confirms that intracranial hypertension represents a rare but life-threatening
      complication of pycnodysostosis. We strongly suggest including systematic
      examination of fundus oculi and monitoring of OFC in the systematic clinical
      follow-up of these patients.

PMID- 20044044
TI  - Finite element analysis performed on radius and tibia HR-pQCT images and
      fragility fractures at all sites in postmenopausal women.
AB  - Assessment of bone strength at the radius by micro-finite element analysis
      (muFEA) has already been associated with wrist fractures. In this study, the
      analysis has been extended to the distal tibia, and to a larger group of subjects
      to examine the association with several types of fragility fractures. We have
      compared muFEA based on in vivo HR-pQCT measurements of BMD and microarchitecture
      at the radius and tibia, in a case-control study involving 101 women with
      prevalent fragility fracture and 101 age-matched controls, from the OFELY cohort.
      Areal BMD was measured by DXA at the radius and the hip. All parameters were
      analyzed in a principal component (PC) analysis (PCA), and associations between
      PCs and fractures were computed as odds ratios (OR [95% CI]) per SD change.
      Radius (tibia) PCA revealed three independent components explaining 76% (77%) of
      the total variability of bone characteristics. The first PC describing bone
      strength and quantity, explained 50% (46%) of variance with an OR=1.84 [1.27
      2.67] (2.92 [1.73-4.93]). The second PC including trabecular microarchitecture,
      explained 16% (10%) of variance, with OR=1.29 [0.90-1.87] (1.11 [0.82-1.52]). The
      third PC related to load distribution explained 10% (20%) of variance, with
      OR=1.54 [1.06-2.24] (1.32 [0.89-1.96]). Moreover, at the radius, vertebral
      fractures were associated with trabecular microarchitecture PC with OR=1.86 [1.14
      3.03], whereas nonvertebral fractures were associated with bone strength and
      quantity PC with OR=2.03 [1.36-3.02]. At the tibia, both vertebral (OR=2.92 [1.61
      5.28]) and nonvertebral fracture (2.64 [1.63-4.27]) were associated to bone
      strength and quantity PC. In conclusion, muFEA parameters at the radius and tibia
      were associated with all types of fragility fractures. We have also shown that
      muFEA parameters obtained with distal tibia data were associated with prevalent
      fractures with a similar magnitude that with parameters obtained at the radius.

PMID- 20044045
TI  - Prospective bone ultrasound patterns during childhood acute lymphoblastic
      leukemia treatment.
AB  - OBJECTIVE: Bone impairment is a well-known complication in childhood acute
      lymphoblastic leukemia (ALL) survivors but less is known about bone dynamics
      during ALL therapy. We longitudinally assessed by Quantitative Ultrasound (QUS)
      skeletal modifications during this treatment. MATERIALS AND METHODS: Forty-four
      newly diagnosed ALL children underwent bone measurement by QUS parameters BTT
      (Bone Transmission Time) and AD-SoS (Amplitude-Dependent Speed of Sound), mainly
      reliant on bone density and cortical thickness, respectively. Measurements were
      performed at diagnosis, and 6, 12, and 24 months thereafter. The occurrence of
      skeletal complications such as fractures, vertebral collapse, osteonecrosis, and
      osteopenia was related to measurement outcome. RESULTS: A rapid deterioration of
      bone properties measured by BTT and AD-SoS was evident in the first semester of
      therapy (p<0.001). Subsequently, the next measurements were characterized by
      progressive uncoupling of the two QUS parameters (p<0.001). These were both
      significantly reduced at the end of therapy (p<0.001). Twelve subjects with in
      treatment skeletal complications displayed an almost two-fold decrease of both
      parameters (p<0.001). BTT decreasing more than 1 Standard Deviation (SD) over 6
      months of therapy was able to predict skeletal complication occurrence (p<0.001).
      CONCLUSION: This report represents the largest longitudinal cohort systematically
      submitted to bone condition assessment from the beginning to the end of therapy
      for childhood ALL. Bone deterioration occurs early and persists throughout
      therapy, consistent with bone properties uncoupling. This pattern possibly
      reflects an initial impairment of both mineral density and cortical thickness
      with a subsequent recovery of this latter. QUS permits an early detection of bone
      deterioration and related skeletal complications in childhood ALL.

PMID- 20044047
TI  - Static pressure drives proliferation of vascular smooth muscle cells via caveolin
      1/ERK1/2 pathway.
AB  - Intimal hyperplasia plays an important role in various types of vascular
      remodeling. Mechanical forces derived from blood flow are associated with the
      proliferation of vascular smooth muscle cells (VSMC). This contributes to many
      vascular disorders such as hypertension, atherosclerosis and restenosis after
      percutaneous transluminal angioplasty (PTA). In this study, we show that static
      pressure induces the proliferation of VSMC and activates its related signal
      pathway. VSMC from a rat aorta were treated with different pressures (0, 60, 90,
      120, 150 and 180 mm Hg) in a custom-made pressure incubator for 24h. The most
      active proliferation of VSMC was detected at a pressure of 120 mm Hg. VSMC was
      also incubated under a static pressure of 120 mm Hg for different time intervals
      (0, 2, 4, 8, 12 and 24h). We found that static pressure significantly stimulates
      VSMC proliferation. Extracellular signal-regulated kinases 1/2 (ERK1/2)
      activation showed a peak at the pressure of 120 mm Hg at 4-h time point.
      Moreover, caveolin-1 expression was significantly inhibited by rising static
      pressure. Downregulation of VSMC proliferation could be found after PD98059
      (ERK1/2 phosphorylation inhibitor) treatment. Our data also showed that a siRNA
      mediated caveolin-1 knock down increased ERK1/2 phosphorylation and VSMC
      proliferation. These results demonstrate that static pressure promotes VSMC
      proliferation via the Caveolin-1/ERK1/2 pathway.

PMID- 20044046
TI  - Decreased osteoclastogenesis and high bone mass in mice with impaired insulin
      clearance due to liver-specific inactivation to CEACAM1.
AB  - Type 2 diabetes is associated with normal-to-higher bone mineral density (BMD)
      and increased rate of fracture. Hyperinsulinemia and hyperglycemia may affect
      bone mass and quality in the diabetic skeleton. In order to dissect the effect of
      hyperinsulinemia from the hyperglycemic impact on bone homeostasis, we have
      analyzed L-SACC1 mice, a murine model of impaired insulin clearance in liver
      causing hyperinsulinemia and insulin resistance without fasting hyperglycemia.
      Adult L-SACC1 mice exhibit significantly higher trabecular and cortical bone
      mass, attenuated bone formation as measured by dynamic histomorphometry, and
      reduced number of osteoclasts. Serum levels of bone formation (BALP) and bone
      resorption markers (TRAP5b and CTX) are decreased by approximately 50%. The L
      SACC1 mutation in the liver affects myeloid cell lineage allocation in the bone
      marrow: the (CD3(-)CD11b(-)CD45R(-)) population of osteoclast progenitors is
      decreased by 40% and the number of (CD3(-)CD11b(-)CD45R(+)) B-cell progenitors is
      increased by 60%. L-SACC1 osteoclasts express lower levels of c-fos and RANK and
      their differentiation is impaired. In vitro analysis corroborated a negative
      effect of insulin on osteoclast recruitment, maturation and the expression levels
      of c-fos and RANK transcripts. Although bone formation is decreased in L-SACC1
      mice, the differentiation potential and expression of the osteoblast-specific
      gene markers in L-SACC1-derived mesenchymal stem cells (MSC) remain unchanged as
      compared to the WT. Interestingly, however, MSC from L-SACC1 mice exhibit
      increased PPARgamma2 and decreased IGF-1 transcript levels. These data suggest
      that high bone mass in L-SACC1 animals results, at least in part, from a negative
      regulatory effect of insulin on bone resorption and formation, which leads to
      decreased bone turnover. Because low bone turnover contributes to decreased bone
      quality and an increased incidence of fractures, studies on L-SACC1 mice may
      advance our understanding of altered bone homeostasis in type 2 diabetes.

PMID- 20044048
TI  - Development of a nasal adenovirus-based vaccine: Effect of concentration and
      formulation on adenovirus stability and infectious titer during actuation from
      two delivery devices.
AB  - A nasal adenovirus-based vaccine is under development. To determine if
      aggregation occurs during vaccination, infectious titer (limiting dilution) and
      capsid integrity (dynamic light scattering) were assessed after extrusion of a
      model vector from two intranasal delivery devices. Preparations of 2.5x10(12) and
      1.25x10(11) virus particles (vp)/ml were studied. Virus aggregated (
      approximately 10%) in the multi-dose vessel. Virus titer dropped by one log.
      Virus in the unit-dose device aggregated ( approximately 1%). Titer remained
      unchanged. Aggregation was concentration dependent. Formulations prevented
      aggregation during actuation, freeze-thaw and long-term storage. The device,
      formulation and dose may significantly influence aggregation and potency of any
      nasal adenovirus 5-based vaccine.

PMID- 20044049
TI  - Cognitive factors and willingness to participate in an HIV vaccine trial among
      HIV-negative injection drug users.
AB  - This cross-sectional study involving a cohort of injection drug users (IDU)
      examined the relationship between cognitive factors (HIV treatment optimism, self
      efficacy and knowledge of vaccine trial concepts) as well as risk factors for
      seroconversion, and willingness to participate (WTP) in a preventive phase 3 HIV
      vaccine trial. Willingness to participate overall was 56%. In a multivariate
      analysis, for a 20-unit increase in a 100-point composite scale, self-efficacy
      was positively related to WTP (adjusted odds ratio [AOR]=1.95, 95% CI=1.40-2.70).
      HIV treatment optimism and knowledge of vaccine trial concepts were unrelated to
      WTP. Aboriginal ethnicity (AOR=3.47, 95% CI=1.68-7.18) and a higher educational
      level (>or=high school) (AOR=1.96, 95% CI=1.07-3.59) were positively related to
      WTP. This study provides information on WTP for an HIV vaccine trial. Limitations
      and future directions are also discussed.

PMID- 20044050
TI  - The effect of routine vaccination on invasive pneumococcal infections in Canadian
      children, Immunization Monitoring Program, Active 2000-2007.
AB  - Active surveillance was conducted by the 12 centers of the Canadian Immunization
      Monitoring Program, Active from 2000-2007 in children 16 years of age and younger
      to determine the influence of 7-valent pneumococcal conjugate immunization
      programs on the prevalence, serotype and antibiotic resistance patterns of
      invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. The
      absolute number of reported IPD cases decreased 48% (p<0.01) over the 8-year
      period and 56% (p<0.01) in children 0-4 years of age. The absolute number of
      reported IPD cases caused by serotypes in the conjugate vaccine decreased 87.5%
      (p<0.01) overall and 92% (p<0.01) in children 0-4 years. Although 6 non-vaccine
      serotypes increased over time, only serotype 19A increased significantly
      (p<0.01). Overall, the proportion of penicillin resistant isolates remained
      unchanged at 17%. Cefotaxime/ceftriaxone resistance remained unchanged at 2% of
      isolates annually. Universal pneumococcal conjugate infant immunization programs
      have dramatically decreased cases of invasive pneumococcal disease.

PMID- 20044051
TI  - Cost-effectiveness of hepatitis A vaccination for individuals with chronic
      hepatitis C.
AB  - The incidence of hepatitis A infection in the United States has decreased
      dramatically in recent years because of childhood immunization programs. A
      decision analysis of the cost-effectiveness of hepatitis A vaccination for adults
      with hepatitis C was conducted. No vaccination strategy is cost-effective for
      adults with hepatitis C using the recent lower anticipated hepatitis A incidence,
      private sector costs, and a cost-effectiveness criterion of $100,000/QALY.
      Vaccination is cost-effective only for individuals who have cleared the hepatitis
      C virus when Department of Veterans Affairs costs are used. The recommendation to
      vaccinate adults with hepatitis C against hepatitis A should be reconsidered.

PMID- 20044052
TI  - A high dosage influenza vaccine induced significantly more neuraminidase antibody
      than standard vaccine among elderly subjects.
AB  - Antibody to the neuraminidase (NA) antigen of influenza viruses has been shown to
      correlate with immunity to influenza in humans and animal models. In a previous
      report, we showed that an inactivated influenza vaccine containing 60microg of
      the hemagglutinin (HA) of each strain induced significantly more serum anti-HA
      antibody among elderly persons than did the standard vaccine containing 15microg
      of the HA of each component. We developed a lectin-based assay for anti-NA
      antibody and used it to measure anti-NA antibody responses among subjects who had
      participated in that study. The high dosage vaccine contained eight times as much
      NA activity as the standard vaccine and induced a significantly higher frequency
      of antibody responses and higher mean postvaccination anti-NA titers to the N1
      and N2 of the A/H1N1 and A/H3N2 viruses in the vaccines than did the standard
      vaccine. Ensuring an increased antibody response to the NA antigen in inactivated
      influenza virus vaccines should increase the protection against influenza. An
      increased quantity of the NA antigen in the vaccine will ensure an increased
      response.

PMID- 20044053
TI  - Induction of HIV-1-specific cellular and humoral immune responses following
      immunization with HIV-DNA adjuvanted with activated apoptotic lymphocytes.
AB  - Delivery of DNA encoding foreign antigens into mammalian cells can induce
      adaptive immune responses. There are currently many DNA-based vaccines in
      clinical trials against infectious diseases and cancer but there is a lack of
      adjuvants for improvement of responses to DNA-based vaccines. Here, we show
      augmented systemic and mucosa-associated B cell responses after immunization with
      a cocktail of seven different plasmids (3 env, 2 gag, 1 rev, 1 RT) combined with
      mitogen activated apoptotic syngeneic lymphocytes in mice. In addition we show
      that apoptotic cells can function as adjuvant for induction of cellular immune
      responses in a magnitude comparable to the cytokine adjuvant GM-CSF in mice.
      These data suggest that activated apoptotic lymphocytes can act independent as
      adjuvants to improve antigen-specific DNA vaccines.

PMID- 20044054
TI  - The role of emerging manufacturers in access to innovative vaccines of public
      health importance.
AB  - The role of developing country manufacturers in assuring global access to
      innovative vaccines was compared to the situation in 2005. These producers now
      supply over 60% of traditional vaccines doses globally and an increasing value
      (up to 15% in 2007) of innovative products. More suppliers are now strong players
      in global market, and an even larger group has potential to do so. These
      manufacturers are not a homogeneous group and most of them are now at a
      crossroads. Decisions made by their management and governments as well as by the
      international community will have a large impact on their existence and future
      and their ability to manufacture innovative vaccines at affordable prices.

PMID- 20044055
TI  - Meningococcal conjugate vaccination among adolescents aged 13-17 years, United
      States, 2007.
AB  - BACKGROUND: An estimated 1000-2000 cases of invasive meningococcal diseases occur
      annually in the United States. In 2005, a new quadrivalent meningococcal
      conjugate vaccine (MCV4) was approved and, because of supply constraints, was
      recommended for routine vaccination of some groups of adolescents. In August
      2007, vaccination recommendations were expanded for all adolescents 11-18 years.
      METHODS: We analyzed data from the 2007 National Immunization Survey-Teen (NIS
      Teen), a nationally representative random digit dialed telephone survey.
      Estimates of MCV4 coverage were assessed from provider-reported vaccination
      histories. A multivariable logistic regression analysis and predictive marginal
      model were performed to identify factors independently associated with MCV4
      vaccination. RESULTS: Provider-reported vaccination histories were available for
      2947 adolescents aged 13-17 years with a response rate of 55.9%. Overall, MCV4
      coverage was 32.4% (95% confidence interval (CI)=30.2-34.7%) in 2007. Vaccination
      coverage was similar among adolescents aged 13-14 years compared to those aged 15
      17 years (32.1% vs. 32.6%, respectively). Coverage was 30.6% for non-Hispanic
      whites, 35.9% for non-Hispanic blacks, and 36.1% for Hispanics; however, these
      variations were not statistically significant. Characteristics independently
      associated with a higher likelihood of MCV4 vaccination included having > or =2
      physician contacts in the past year, having a well child visit at age 11-12
      years, and ever having a doctor recommendation for meningitis vaccination of the
      adolescent. CONCLUSIONS: In 2007, MCV4 coverage among 13-17 years old increased
      20.7 percentage points from 2006. Achieving high vaccination coverage among
      adolescents will be challenging. Targeting adolescents with no health insurance
      and no recent healthcare provider visits may be important to increase coverage.

PMID- 20044057
TI  - Re: Hepatitis A and E: Update on prevention and epidemiology.

PMID- 20044056
TI  - Frequency of factor H-binding protein modular groups and susceptibility to cross
      reactive bactericidal activity in invasive meningococcal isolates.
AB  - Meningococcal factor H-binding protein (fHbp) is a promising vaccine candidate
      that elicits serum bactericidal antibodies in humans. Based on sequence
      variability of the entire protein, fHbp has been divided into three variant
      groups or two sub-families. We recently reported that the fHbp architecture was
      modular, consisting of five variable segments, each encoded by genes from one of
      two lineages. Based on combinations of segments from different lineages, all 70
      known fHbp sequence variants could be classified into one of six modular groups.
      In this study, we analyzed sequences of 172 new fHbp variants that were available
      from public databases. All but three variants could be classified into one of the
      six previously described modular groups. Among systematically collected invasive
      group B isolates from the U.S. and Europe, modular group I overall was most
      common (60%) but group IV (natural chimeras) accounted for 23% of UK isolates and
      <1% of U.S. isolates (P<0.0001). Mouse antisera to recombinant fHbp from each of
      the modular groups showed modular group-specific bactericidal activity against
      strains with low fHbp expression but had broader activity against strains with
      higher fHbp expression. Thus both modular group and relative expression of fHbp
      affected strain susceptibility to anti-fHbp bactericidal activity. The results
      confirmed the modular architecture of fHbp and underscored its importance for the
      design of broadly protective group B vaccines in different regions.

PMID- 20044058
TI  - Expected and unexpected adverse effects H1N1 vaccination for health care workers
      in a university hospital.

PMID- 20044060
TI  - Mothers' preferences and willingness to pay for vaccinating daughters against
      human papillomavirus.
AB  - A choice-format, conjoint-analysis survey was developed and fielded to estimate
      how features of human papillomavirus (HPV) vaccines affect mothers' perceived
      benefit and stated vaccine uptake for daughters. Data were collected from a
      national sample of 307 U.S. mothers of girls aged 13-17 years who had not yet
      received an HPV vaccine. Preferences for four features of HPV vaccines were
      evaluated: protection against cervical cancer, protection against genital warts,
      duration of protection, and cost. We estimate that mean maximum willingness-to
      pay (WTP)-an economic measure of the total benefits to consumers-for current HPV
      vaccine technology ranges between $560 and $660. All vaccine features were
      statistically significant determinants of WTP and uptake. Mothers were willing to
      pay $238 more for a vaccine that provides 90% protection for genital warts
      relative to a vaccine that provides no protection against warts. WTP for lifetime
      protection vs. 10 years protection was $245. Mothers strongly valued greater
      cervical cancer efficacy, with 100% protection against cervical cancers the most
      desired feature overall. Adding a second HPV vaccine choice to U.S. consumers'
      alternatives is predicted to increase stated uptake by 16%. Several features were
      significantly associated with stated choices and uptake: age of mother,
      race/ethnicity, household income, and concern about HPV risks. These findings
      provide new data on how HPV vaccines are viewed and valued by mothers, and how
      uptake may change in the context of evolving vaccine technology and as new data
      are reported on duration and efficacy.

PMID- 20044059
TI  - Identification of immunodominant antigens of Chlamydia trachomatis using proteome
      microarrays.
AB  - Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen
      in the world. In order to control this infection there is an urgent need to
      formulate a vaccine. Identification of protective antigens is required to
      implement a subunit vaccine. To identify potential antigen vaccine candidates,
      three strains of mice, BALB/c, C3H/HeN and C57BL/6, were inoculated with live and
      inactivated C. trachomatis mouse pneumonitis (MoPn) by different routes of
      immunization. Using a protein microarray, serum samples collected after
      immunization were tested for the presence of antibodies against specific
      chlamydial antigens. A total of 225 open reading frames (ORF) of the C.
      trachomatis genome were cloned, expressed, and printed in the microarray. Using
      this protein microarray, a total of seven C. trachomatis dominant antigens were
      identified (TC0052, TC0189, TC0582, TC0660, TC0726, TC0816 and, TC0828) as
      recognized by IgG antibodies from all three strains of animals after
      immunization. In addition, the microarray was probed to determine if the antibody
      response exhibited a Th1 or Th2 bias. Animals immunized with live organisms
      mounted a predominant Th1 response against most of the chlamydial antigens while
      mice immunized with inactivated Chlamydia mounted a Th2-biased response. In
      conclusion, using a high throughput protein microarray we have identified a set
      of novel proteins that can be tested for their ability to protect against a
      chlamydial infection.

PMID- 20044061
TI  - LAIV efficacy in military recruits.

PMID- 20044063
TI  - Detecting intra- and inter-categorical structure in semantic concepts using
      HICLAS.
AB  - In this paper, we investigate the hypothesis that people use feature correlations
      to detect inter- and intra-categorical structure. More specifically, we study
      whether it is plausible that people strategically look for a particular type of
      feature co-occurrence that can be represented in terms of rectangular patterns of
      1s and 0s in a binary feature by exemplar matrix. Analyzing data from the Animal
      and Artifact domains, we show that the HICLAS model, which looks for such
      rectangular structure and which therefore models a cognitive capacity of
      detecting feature co-occurence in large data bases of features characterizing
      exemplars, succeeds rather well in predicting inter- and intra-categorical
      structure.

PMID- 20044064
TI  - Social inhibition of return.
AB  - Responses to a target stimulus can be slower when it appears in the same rather
      than a different location to a previous event, an effect known as inhibition of
      return (IOR). Recently, it has been shown that when two people alternate
      responses to a target, one person's responses are slower when they are directed
      to the same locations as their partner's previous response. The present study
      sought to investigate this highly novel effect, which we term social IOR (SIOR),
      in relation to what is known of IOR in individuals performing alone. We found
      that only a real conspecific can induce SIOR in another person, whereas an
      animated conspecific cannot. Additionally, SIOR emerges at locations to which a
      conspecific has been inferred to respond, even when direct observation of his/her
      responses is prevented. Finally, SIOR can be induced without the abrupt visual
      transients normally associated with the generation of IOR. These findings suggest
      that SIOR is the result of stronger activations of IOR mechanisms, or that it is
      subserved by entirely separate inhibitory processes.

PMID- 20044062
TI  - The multifunctional choroid.
AB  - The choroid of the eye is primarily a vascular structure supplying the outer
      retina. It has several unusual features: It contains large membrane-lined
      lacunae, which, at least in birds, function as part of the lymphatic drainage of
      the eye and which can change their volume dramatically, thereby changing the
      thickness of the choroid as much as four-fold over a few days (much less in
      primates). It contains non-vascular smooth muscle cells, especially behind the
      fovea, the contraction of which may thin the choroid, thereby opposing the
      thickening caused by expansion of the lacunae. It has intrinsic choroidal
      neurons, also mostly behind the central retina, which may control these muscles
      and may modulate choroidal blood flow as well. These neurons receive sympathetic,
      parasympathetic and nitrergic innervation. The choroid has several functions: Its
      vasculature is the major supply for the outer retina; impairment of the flow of
      oxygen from choroid to retina may cause Age-Related Macular Degeneration. The
      choroidal blood flow, which is as great as in any other organ, may also cool and
      warm the retina. In addition to its vascular functions, the choroid contains
      secretory cells, probably involved in modulation of vascularization and in growth
      of the sclera. Finally, the dramatic changes in choroidal thickness move the
      retina forward and back, bringing the photoreceptors into the plane of focus, a
      function demonstrated by the thinning of the choroid that occurs when the focal
      plane is moved back by the wearing of negative lenses, and, conversely, by the
      thickening that occurs when positive lenses are worn. In addition to focusing the
      eye, more slowly than accommodation and more quickly than emmetropization, we
      argue that the choroidal thickness changes also are correlated with changes in
      the growth of the sclera, and hence of the eye. Because transient increases in
      choroidal thickness are followed by a prolonged decrease in synthesis of
      extracellular matrix molecules and a slowing of ocular elongation, and attempts
      to decouple the choroidal and scleral changes have largely failed, it seems that
      the thickening of the choroid may be mechanistically linked to the scleral
      synthesis of macromolecules, and thus may play an important role in the
      homeostatic control of eye growth, and, consequently, in the etiology of myopia
      and hyperopia.

PMID- 20044065
TI  - Prenatal intraabdominal bowel dilation is associated with postnatal
      gastrointestinal complications in fetuses with gastroschisis.
AB  - OBJECTIVE: The purpose of this study was to determine whether prenatal
      intraabdominal bowel dilation (IBD) is associated with increased postnatal
      complications in fetuses with gastroschisis. STUDY DESIGN: A retrospective review
      was performed on all maternal-fetus pairs with prenatally diagnosed gastroschisis
      that was treated at the University of California San Francisco from 2002-2008.
      Postnatal outcomes were compared between fetuses with and without IBD. RESULTS:
      Forty-three of 61 maternal-fetal pairs met the criteria for inclusion. Sixteen
      fetuses (37%) had evidence of IBD. Fetuses with IBD were significantly more
      likely to have postnatal bowel complications (38% vs 7%; P = .037). The presence
      of multiple loops of IBD (n = 6) as opposed to a single loop (n = 10) was
      associated highly with bowel complications and increased time to full enteral
      feeding and length of hospital stay (100% vs 0% [P = .001]; 44 vs 23 days [P =
      .034]; 69 vs 27 days [P = .001], respectively). CONCLUSION: IBD is associated
      with increased postnatal complications in infants with prenatally diagnosed
      gastroschisis; however, this association seems to be limited to those with
      multiple loops of dilated intraabdominal bowel.

PMID- 20044066
TI  - Smoking behavior in women with locally advanced cervical carcinoma: a Gynecologic
      Oncology Group study.
AB  - OBJECTIVE: The purpose of this study was to assess cigarette use and
      environmental smoke exposure in women with cervical cancer. STUDY DESIGN: Smoking
      behavior was recorded prospectively in a clinical trial of women with locally
      advanced cervical carcinoma. RESULTS: Of 315 participants, 133 women (42%) were
      current smokers; 72 women (23%) were former smokers, and 110 women (35%) were
      never smokers. Current smokers began smoking earlier (16 vs 18 years; P = .009),
      for more years (29 vs 24 years; P = .005), and in greater amounts (20 vs 11
      cigarettes/d; P < .001) than former smokers. Active smokers lived more often with
      another smoker (63.3%), compared with former smokers (35.0%; P < .001) or never
      smokers (28.7%; P < .001). Agreement between self-report and urine cotinine level
      was high (kappa = 0.872; P < .001). A significant decrease in cotinine level
      during treatment occurred in 5.2% of current smokers. CONCLUSION: Prevalence of
      smoking and tobacco consumption was twice that of the North American female
      population. Few smokers quit or decreased consumption during treatment.

PMID- 20044067
TI  - Electronic prescribing influence on calcium supplementation: a randomized
      controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine whether an electronic
      prescription for over-the-counter calcium supplements increases compliance. STUDY
      DESIGN: Two hundred forty-five patients from 19-50 years of age who underwent
      annual gynecologic examinations were assigned randomly to either verbal
      counseling about the use of a calcium carbonate with vitamin D supplement (n =
      122) or verbal counseling and an electronic prescription (n = 123). Telephone
      interviews at 3 and 6 months determined compliance. RESULTS: Women who received
      the electronic prescription were significantly more likely to use calcium
      supplementation than control subjects at both 3 and 6 months. At 3 months, 66.0%
      of women who received an electronic prescription reported compliance (P = .001).
      At 6 months, 57.0% of the participants were compliant (P = .001). At 6 months,
      women who were given the electronic prescription were 2.2 times more likely to
      report having taken the calcium than were control subjects (95% confidence
      interval, 1.5-3.1). CONCLUSION: An electronic prescription for over-the-counter
      calcium supplements is associated with a significant increase in compliance,
      compared with verbal counseling alone.

PMID- 20044068
TI  - Forgotten "father of progesterone".

PMID- 20044069
TI  - The pituitary stalk interruption syndrome: endocrine features and benefits of
      growth hormone therapy.
AB  - INTRODUCTION: Childhood anterior-pituitary insufficiency has many causes
      (malformative, genetic, traumatic, tumoral...). One particular entity can be
      clearly identified: pituitary stalk interruption syndrome (PSIS). The aim of our
      study was to analyse the long-term evolution of patients with PSIS. PATIENTS AND
      METHODS: The records of all the children followed at Dijon University Hospital
      between 1990 and 2008 who underwent brain magnetic resonance imaging (MRI) and
      endocrinological evaluation that revealed a growth hormone (GH) deficiency were
      analysed. We thus selected 14 children diagnosed with PSIS according to the
      results of MRI. We studied the perinatal characteristics of these patients, then
      the auxological and the endocrine evolutions, before the initiation of GH therapy
      and then after 1 and 3 years of treatment and during the last evaluation.
      RESULTS: Fourteen children were diagnosed with PSIS at a mean+/-sd age of 3.2+/
      3.5 years, five of whom being diagnosed during the first 2 months of life.
      Growth, as well as other anterior-pituitary deficiencies, was systematically
      followed up two to four times a year depending on the clinical context. The
      results in terms of endocrinology were analysed in all 14 children, and with
      regard to auxology in the 10 children who received GH therapy for at least 12
      months, with a mean of 8.3+/-4.2 years and at a mean maintenance posology of
      0.22+/-0.02mg/kg per week. Among the 14 children, 12 had complete GH deficiency
      while two had a partial deficiency. Nine had multiple anterior pituitary
      deficiencies, diagnosed at the same time or later in five and four of them
      respectively. A clinical picture of panhypopituitarism was found in the infants
      who were diagnosed with PSIS in their first months of life. In the 10 children
      who were treated for at least 12 months, the height before treatment was -3.1+/
      0.8 standard deviation score (SDS). At the last consultation, the total gain in
      height was +2.5+/-0.9 SDS compared to the distance to target height of +2.7+/-0.6
      SDS. The height gain after 1 year of treatment corresponded to 60% of the total
      gain. CONCLUSION: In children with PSIS, the other anterior pituitary
      deficiencies are often associated with GH deficiency and sometimes during the
      first month of life. These functions therefore require to be carefully followed
      early, periodically and in the long term. Growth in these children responds
      particularly well to GH therapy, in particular during the first year.

PMID- 20044070
TI  - The interleukin 1 beta (IL1B) gene is associated with failure to achieve
      remission and impaired emotion processing in major depression.
AB  - BACKGROUND: Accumulating evidence suggests the involvement of inflammatory
      processes and cytokines in particular in the pathophysiology of major depression
      (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and
      anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been
      suggested as a predictor of treatment response. This study investigated the
      association between genetic variants of the interleukin 1 beta (IL1B) gene and
      amygdala and ACC responsiveness to emotional stimuli and response to
      antidepressant treatment. METHODS: In this analysis, 256 Caucasian patients with
      MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and
      rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6
      weeks was defined as remission (< or = 7 on the Hamilton Rating Scale for
      Depression-21-question) and response (>50% decrease on Hamilton Rating Scale for
      Depression-21-question). Brain activity under visual presentation of emotional
      faces was assessed in a subsample of 32 depressed patients by means of functional
      magnetic resonance imaging at 3 T. RESULTS: Pharmacogenetic analyses show
      significant associations of the GG genotypes of single nucleotide polymorphisms
      (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2-4.3) and rs1143643
      (odds ratio = 3.1; 95% confidence interval 1.3-7.8) (compared with the AA
      genotype) with nonremission after 6 weeks. The imaging analyses show that the
      number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with
      reduced responsiveness of the amygdala and ACC to emotional stimulation.
      CONCLUSIONS: The present study suggests a negative effect of the IL1B gene on
      pharmacological response and amygdala and ACC function involving the same
      genotypes of two SNPs (rs16944, rs116343), which taken together increase the risk
      of nonremission over 6 weeks of antidepressant treatment in MDD.

PMID- 20044071
TI  - Nosce te ipsum: On the efficacy of transcranial magnetic stimulation in major
      depressive disorder.

PMID- 20044072
TI  - Deep brain stimulation in the subgenual cingulate cortex for an intractable
      eating disorder.

PMID- 20044073
TI  - Hypersensitivity to reward in problem gamblers.
AB  - BACKGROUND: Recent research has begun to examine the neurophysiologic basis of
      pathological gambling. However, direct evidence of a behavioral deficit and an
      accompanying neurofunctional deviation in a realistic gambling context such as
      Black Jack has not yet been reported. METHODS: Electroencephalogram was recorded
      while 20 problem gamblers and 21 control participants played a computerized
      version of Black Jack. Participants were asked to decide at point scores between
      11 and 21 whether they wanted to take another card ("hit") to arrive closer to 21
      than the opponent (simulated by computer) or not to take another card ("sit") to
      avoid going over 21 ("bust"). RESULTS: At a critical point score of 16, problem
      gamblers decided more often to hit despite losses due to a bust on the preceding
      trial, whereas control participants decided more often to sit under these
      conditions. Furthermore, problem gamblers showed more reward-related positive
      amplitudes in the event-related brain potential than control participants after
      successful hit decisions at 16. CONCLUSIONS: Here we provide experimental
      evidence for high-risk taking behavior in gamblers and its correlate in event
      related brain potentials. Our results suggest that high-risk-taking behavior in
      problem gamblers is associated with an increased reward-related neural response
      to infrequent successes of this behavior.

PMID- 20044074
TI  - Basolateral amygdala modulates terminal dopamine release in the nucleus accumbens
      and conditioned responding.
AB  - BACKGROUND: Dopamine signaling in the nucleus accumbens (NAc) is essential for
      goal-directed behaviors and primarily arises from burst firing of ventral
      tegmental area neurons. However, the role of associative neural substrates such
      as the basolateral amygdala (BLA) in regulating phasic dopamine release in the
      NAc, particularly during reward seeking, remains unknown. METHODS: Male Sprague
      Dawley rats learned to discriminate two cues: a discriminative stimulus (DS) that
      predicted sucrose reinforcement contingent upon a lever press and a nonassociated
      stimulus (NS) that predicted a second lever never reinforced with sucrose.
      Following training, a test session was completed in which NAc dopamine was
      measured using fast-scan cyclic voltammetry in conjunction with inactivation of
      the ipsilateral BLA (gamma-aminobutyric acid agonists; baclofen/muscimol) to
      determine the contribution of BLA activity to dopamine release in the NAc core
      during the task. RESULTS: Under vehicle conditions, DS and NS presentation
      elicited dopamine release within the NAc core. The DS evoked significantly more
      dopamine than the NS. Inactivation of the BLA selectively attenuated the
      magnitude of DS-evoked dopamine release, concurrent with an attenuation of DS
      evoked conditioned approaches. Other behavioral responses (e.g., lever pressing)
      and dopamine release concomitant with those events were unaltered by BLA
      inactivation. Furthermore, neither ventral tegmental area electrically stimulated
      dopamine release nor the probability of high concentration dopamine release
      events was altered following BLA inactivation. CONCLUSIONS: These results
      demonstrate that the BLA terminally modulates dopamine signals within the NAc
      core under specific, behaviorally relevant conditions, illustrating a functional
      mechanism by which the BLA selectively facilitates responding to motivationally
      salient environmental stimuli.

PMID- 20044075
TI  - Nicotine dependence is characterized by disordered reward processing in a network
      driving motivation.
AB  - BACKGROUND: Drug addiction is characterized by an unhealthy priority for drug
      consumption with a compulsive, uncontrolled drug-intake pattern due to a
      disordered motivational system. However, only some individuals become addicted,
      whereas others maintain regular but controlled drug use. Whether the transition
      occurs might depend on how individuals process drug relative to nondrug reward.
      METHODS: We applied functional magnetic resonance imaging to measure
      mesocorticolimbic activity to stimuli predicting monetary or cigarette reward,
      together with behavioral assessment of subsequent motivation to obtain the
      respective reward on a trial-by-trial basis, in 21 nicotine-dependent and 21
      nondependent, occasional smokers. RESULTS: Occasional smokers showed increased
      reactivity of the mesocorticolimbic system to stimuli predicting monetary reward
      relative to cigarette reward and subsequently spent more effort to obtain money.
      In the group of dependent smokers, we found equivalent anticipatory activity and
      subsequent instrumental response rates for both reward types. Additionally,
      anticipatory mesocorticolimbic activation predicted subsequent motivation to
      obtain reward. CONCLUSIONS: This imbalance in the incentive salience of drug
      relative to nondrug reward-predicting cues, in a network that drives motivation
      to obtain reward, could represent a central mechanism of drug addiction.

PMID- 20044077
TI  - Metal-carboxylate interactions in metal-alginate complexes studied with FTIR
      spectroscopy.
AB  - FTIR spectroscopy was used in order to obtain information about metal-carboxylate
      interactions in metal-alginate complexes of alginic acid and sodium alginate from
      the brown algae Laminaria digitata after crosslinking with Ca(2+), Cu(2+),
      Cd(2+), Zn(2+), Ni(2+) and Pb(2+). From the frequencies of the characteristic
      peaks for asymmetric COO stretching vibration (nu(asym)(COO(-)) and symmetric COO
      stretching vibration (nu(sym)(COO(-))) a 'pseudo bridged' unidentate coordination
      with intermolecular hydrogen bonds is proposed for the metal-carboxylate
      complexes in polyguluronic regions while for the polymannuronic regions the
      bidentate bridging coordination was proposed. The PIB factor introduced
      previously as a relationship between metal sorption and frequencies of the
      asymmetric vibrations was found not to correlate with sorption capacity or any
      other physical property of the metal-alginate complexes studied.

PMID- 20044078
TI  - Synthesis of densely functionalised C-glycosides by a tandem oxy Michael addition
      Wittig olefination pathway.
AB  - Wittig olefination of 5,6-dideoxy-5,6-anhydro-6-nitro-D-glucofuranose (5)
      triggered a concomitant cyclisation via oxy Michael addition of the C2-hydroxyl
      group resulting in the formation of C-vinyl glycosides with Z-olefinic geometry.

PMID- 20044076
TI  - Brain injury and recovery following binge ethanol: evidence from in vivo magnetic
      resonance spectroscopy.
AB  - BACKGROUND: The binge-drinking model in rodents using intragastric injections of
      ethanol (EtOH) for 4 days results in argyrophilic corticolimbic tissue
      classically interpreted as indicating irreversible neuronal degeneration.
      However, recent findings suggest that acquired argyrophilia can also identify
      injured neurons that have the potential to recover. The current in vivo magnetic
      resonance (MR) imaging and spectroscopy study was conducted to test the
      hypothesis that binge EtOH exposure would injure but not cause the death of
      neurons as previously ascertained postmortem. METHODS: After baseline MR
      scanning, 11 of 19 rats received a loading dose of 5 g/kg EtOH via oral gavage,
      then a maximum of 3 g/kg every 8 hours for 4 days, for a total average cumulative
      EtOH dose of 43 +/- 1.2 g/kg and average blood alcohol levels of 258 +/- 12
      mg/dL. All animals were scanned after 4 days of gavage (post-gavage scan) with
      EtOH (EtOH group) or dextrose (control [Con] group) and again after 7 days of
      abstinence from EtOH (recovery scan). RESULTS: Tissue shrinkage at the post
      gavage scan was reflected by significantly increased lateral ventricular volume
      in the EtOH group compared with the Con group. At the post-gavage scan, the EtOH
      group had lower dorsal hippocampal N-acetylaspartate and total creatine and
      higher choline-containing compounds than the Con group. At the recovery scan,
      neither ventricular volume nor metabolite levels differentiated the groups.
      CONCLUSIONS: Rapid recovery of ventricular volume and metabolite levels with
      removal of the causative agent argues for transient rather than permanent effects
      of a single EtOH binge episode in rats.

PMID- 20044079
TI  - Straightforward synthesis of novel Akt inhibitors based on a glucose scaffold.
AB  - Glucose-based analogues of phosphatidylinositol 3-phosphate were
      straightforwardly synthesised from 2,3,4,6-tetra-O-acetyl-d-glucosyl bromide as
      protein kinase B (PKB/Akt) inhibitors. beta-d-Glucuronyl diethyl phosphoramidate
      was identified as a promising hit through biological screening in two different
      cellular systems. In addition, RNA interference experiments (siRNA) provide
      evidence of the ability of the compound to exert biological effects specifically
      through Akt signalling.

PMID- 20044080
TI  - From D-xylose to terminal polyols: a simple synthetic route.
AB  - A simple and efficient synthetic approach toward different terminal alkyl
      tetraols and triols, starting from D-xylose, is described. The opening of the
      oxetane ring in a suitably protected 3,5-anhydro-D-xylose derivative with
      Grignard reagents leads to D-xylose-derived 5-deoxy-5-C-alkyl derivatives, which
      are suitable for reduction to terminal polyols after protecting group hydrolysis.

PMID- 20044081
TI  - N-Glycosylation profiling of turtle egg yolk: expression of galabiose structure.
AB  - To understand the roles of species-specific carbohydrates, systematic studies of
      interspecific glycan analyses are imperative. An extensive series of glycomics
      studies on approximately 180 kinds of bird eggs have demonstrated that 60-70% of
      the birds, which are closely related in phylogeny, express the alpha-Galp-(1-->4)
      Galp structure on their egg glycoproteins. This prompted us to investigate the
      glycosylation profiles of eggs from an evolutionarily related organism, a sea
      turtle (reptilian). We performed N-glycosylation profiling of turtle egg yolk by
      using HPLC mapping in conjunction with mass spectrometric methods and thereby
      demonstrated that the alpha-Galp-(1-->4)-Galp groups are displayed on
      approximately 38% of total N-glycans. Our findings suggest that the ability to
      express the galabiose structure was acquired at an early stage of diversification
      in amniotes.

PMID- 20044082
TI  - Synthesis of trisaccharides containing internal galactofuranose O-linked in
      Trypanosoma cruzi mucins.
AB  - The trisaccharides beta-D-Galf-(1-->2)-beta-D-Galf-(1-->4)-D-GlcNAc (5) and beta
      D-Galp-(1-->2)-beta-D-Galf-(1-->4)-D-GlcNAc (6) constitute novel structures
      isolated as alditols when released by reductive beta-elimination from mucins of
      Trypanosoma cruzi (Tulahuen strain). Trisaccharides 5 and 6 were synthesized
      employing the aldonolactone approach. Thus, a convenient D-galactono-1,4-lactone
      derivative was used for the introduction of the internal galactofuranose and the
      trichloroacetimidate method was employed for glycosylation reactions. Due to the
      lack of anchimeric assistance on O-2 of the galactofuranosyl precursor,
      glycosylation studies were performed under different conditions. The nature of
      the solvent strongly determined the stereochemical course of the glycosylation
      reactions when the galactofuranosyl donor was substituted either by 2-O-Galp or 2
      O-Galf.

PMID- 20044083
TI  - Tumor classification by combining PNN classifier ensemble with neighborhood rough
      set based gene reduction.
AB  - Since Golub applied gene expression profiles (GEP) to the molecular
      classification of tumor subtypes for more accurately and reliably clinical
      diagnosis, a number of studies on GEP-based tumor classification have been done.
      However, the challenges from high dimension and small sample size of tumor
      dataset still exist. This paper presents a new tumor classification approach
      based on an ensemble of probabilistic neural network (PNN) and neighborhood rough
      set model based gene reduction. Informative genes were initially selected by gene
      ranking based on an iterative search margin algorithm and then were further
      refined by gene reduction to select many minimum gene subsets. Finally, the
      candidate base PNN classifiers trained by each of the selected gene subsets were
      integrated by majority voting strategy to construct an ensemble classifier.
      Experiments on tumor datasets showed that this approach can obtain both high and
      stable classification performance, which is not too sensitive to the number of
      initially selected genes and competitive to most existing methods. Additionally,
      the classification results can be cross-verified in a single biomedical
      experiment by the selected gene subsets, and biologically experimental results
      also proved that the genes included in the selected gene subsets are functionally
      related to carcinogenesis, indicating that the performance obtained by the
      proposed method is convincing.

PMID- 20044084
TI  - Detecting novel hypermethylated genes in breast cancer benefiting from feature
      selection.
AB  - The aberrant hypermethylation of CpG islands in promoter regions of genes plays
      an important role in the onset and progression of Breast cancer. Meanwhile, it is
      highly associated with human genomic features. Two feature selection algorithms:
      t-test and CfsSubsetEval were used to obtain efficient feature subsets. We
      discovered 14 significant feature subsets by CfsSubsetEval, which can distinguish
      hypermethylated genes from control genes. As a result, 393 unconfirmed
      hypermethylated genes in Breast cancer were prioritized. These genes were
      assigned the hypermethylated scores and were supported by literature and Gene
      Ontology enrichment. This paper suggests that the feature subsets could be served
      as discriminating genomic markers to infer novel hypermethylated genes in cancer
      potentially.

PMID- 20044085
TI  - Impact of embryo replacement depth on in vitro fertilization and embryo transfer
      outcomes.
AB  - OBJECTIVE: To investigate the impact of embryo replacement depth on IVF and
      embryo transfer outcomes. DESIGN: Retrospective analysis (May 2005 to November
      2008) of 5,055 ultrasound-guided embryo transfers belonging to 3,930 infertile
      couples. The distance between the fundal endometrial surface and the catheter tip
      was measured and accordingly, patients were divided into five groups. SETTING:
      Anatolia IVF Center, Ankara, Turkey. PATIENT(S): All patients enrolled in the IVF
      program undergoing embryo transfer. INTERVENTION(S): No patient received any
      additional procedure or intervention. MAIN OUTCOME MEASURE(S): Clinical pregnancy
      rate (PR) and ongoing PR. RESULT(S): Mean total number of embryos transferred in
      groups 4 and 5 were significantly higher than in groups 2 and 3. Analysis of PRs
      and outcome of gestations in the five groups studied yielded similar PRs in all
      groups except for group 1. CONCLUSION(S): Pregnancy rates and ongoing PRs are
      higher if the embryos are replaced at a distance >10 mm from the fundal
      endometrial surface. In addition because significantly more embryos were replaced
      in cycles where the transfers occurred at a distance of >20 mm, a distance>10 mm
      to <20 mm seems to be the best site for embryo transfer to achieve higher PRs.

PMID- 20044086
TI  - The polymorphism Trp719Arg in the kinesin-like protein 6 is associated with the
      presence of late outgrowth endothelial progenitor cells in acute myocardial
      infarction.

PMID- 20044087
TI  - Angiotensin II receptor antagonism with telmisartan increases number of
      endothelial progenitor cells in normotensive patients with coronary artery
      disease: a randomized, double-blind, placebo-controlled study.
AB  - INTRODUCTION: Circulating endothelial progenitor cells (EPCs) provide an
      endogenous repair mechanism of the dysfunctional endothelium and therefore can
      play a crucial role in the pathophysiology of coronary artery disease (CAD).
      Angiotensin II receptor antagonism has been shown to be able to increase EPCs in
      hypertension but its effect in patients with CAD is unknown. Aim of this study
      was to evaluate whether telmisartan, an angiotensin II receptor antagonist, can
      modify the number of subpopulations of EPCs and may in turn affect the
      endothelial function of normotensive patients with CAD. METHODS: In a prospective
      double-blind parallel group study, 40 normotensive patients with CAD were
      randomly treated with telmisartan (80 mg) or placebo for 4 weeks at time of
      coronary angiography. Measurements of EPCs and assessment of flow-mediated
      dilatation (FMD) of the brachial artery was performed before and after therapy.
      RESULTS: Absolute number of EPCs was similar at baseline in the telmisartan and
      placebo groups. After 4 weeks treatment, CD34+/KDR+/CD45- cells increased
      significantly in the telmisartan group (from 0.010+/-0.003 to 0.014+/-0.004%,
      P=0.0001) but not in the placebo group (from 0.009+/-0.004 to 0.009+/-0.005%,
      NS). Similarly, CD133+/KDR+/CD45- cells raised significantly with telmisartan
      (from 0.003+/-0.002 to 0.006+/-0.002%, P=0.0001) but not with placebo (from
      0.004+/-0.003 to 0.003+/-0.002%, NS). Also, CD14+/CD45+ cells increased
      significantly with telmisartan (from 0.005+/-0.002 to 0.008+/-0.002%, P=0.0001)
      and were unchanged with placebo (0.006+/-0.002 vs. 0.005+/-0.003%, NS). FMD
      improved significantly in patients who received telmisartan (10.4+/-3.9%,
      P=0.0015 vs. baseline) but did not change in the placebo group (5.9+/-2.8%;
      P=0.32 vs. baseline; telmisartan vs. placebo, P=0.002). A significant positive
      correlation was found in the telmisartan group between the improvement in FMD and
      the increase in CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells (r=0.55,
      P<0.01, and r=0.49, P<0.05, respectively). CONCLUSION: Angiotensin II receptor
      antagonism with telmisartan increases the number of regenerative EPCs and
      improves endothelial function in normotensive patients with CAD. These novel
      effects are interrelated and can explain, at least in part, why telmisartan has
      beneficial cardiovascular effects independent of its blood pressure lowering
      action.

PMID- 20044089
TI  - Atomistic simulation of nanomechanical properties of Alzheimer's Abeta(1-40)
      amyloid fibrils under compressive and tensile loading.
AB  - In addition to being associated with severe degenerative diseases, amyloids show
      exceptional mechanical properties including great strength, sturdiness and
      elasticity. However, thus far physical models that explain these properties
      remain elusive, and our understanding of molecular deformation and failure
      mechanisms of individual amyloid fibrils is limited. Here we report a series of
      molecular dynamics simulations, carried out to analyze the mechanical response of
      two-fold symmetric Abeta(1-40) amyloid fibrils, twisted protein nanofilaments
      consisting of a H-bonded layered structure. We find a correlation of the
      mechanical behavior with chemical and nanostructural rearrangements of the fibril
      during compressive and tensile deformation, showing that the density of H-bonds
      varies linearly with the measured strain. Further, we find that both compressive
      and tensile deformation is coupled with torsional deformation, which is
      manifested in a strong variation of the interlayer twist angle that is found to
      be proportional to both the applied stress and measured strain. In both
      compression and tension we observe an increase of the Young's modulus from 2.34
      GPa (for less than 0.1% strain in compression and 0.2% strain in tension), to
      12.43 GPa for compression and 18.05 GPa for tension. The moduli at larger
      deformation are in good agreement with experimental data, where values in the
      range of 10-20 GPa have been reported. Our studies confirm that amyloids feature
      a very high stiffness, and elucidate the importance of the chemical and
      structural rearrangements of the fibrils during deformation.

PMID- 20044088
TI  - Association of plasma soluble E-selectin and adiponectin with carotid plaque in
      patients with systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is associated with premature
      atherosclerosis but the mechanisms underlying this association are not
      understood. The role of endothelial dysfunction is hypothesized. METHODS: In
      predominantly non-Caucasian patients with SLE (N=119) and controls (N=71),
      carotid ultrasonography was performed and circulating endothelial cells (CECs),
      soluble endothelial protein C receptor and gene polymorphism at A6936G, soluble E
      selectin (sE-selectin), and adiponectin were assessed. RESULTS: Carotid plaque
      was more prevalent among patients than controls (43% vs 17%, p=0.0002). Mean CCA
      IMT was greater in patients compared to controls (0.59+/-0.19 mm vs 0.54+/-0.11
      mm, p=0.03). Among SLE patients, plaque was not associated with smoking, body
      mass index, LDL, triglycerides, homocysteine, C-reactive protein, anti-ds DNA
      antibody, C3, C4, SLE activity, or medications. Age and levels of soluble E
      selectin and adiponectin were significantly higher in the SLE patients with
      plaque compared to those without plaque in univariate and multivariate analyses.
      sE-selectin and adiponectin were found to serve as independent predictors of
      carotid plaque and that elevations were persistent over more than one visit.
      Unexpectedly, these biomarkers were present despite clinical quiescence.
      CONCLUSION: Premature atherosclerosis is a consistent feature of SLE and extends
      across ethnicities. Higher levels of adiponectin may represent a physiological
      attempt to limit further endothelial damage already reflected by the elevation in
      sE-selectin and the observed increase in plaque represents overwhelming of this
      reparative process by atherogenic stimuli.

PMID- 20044090
TI  - No need for particle tracing: from accumulating fluid properties to novel blood
      coagulation model in the lattice Boltzmann method.
AB  - The accumulation of a fluid property from the standpoint of a particle moving
      with non-steady fluid flow (i.e., platelet/blood-cell damage index in pulsating
      blood flow) is a challenged computational problem due to the current need for
      particle-tracing methods. The method we developed (dubbed VPI) enables the
      approximation of the Lagrangian integral in real-time for any point in space and
      time for the entire domain and which is easily integrated into the the lattice
      Boltzmann method. As an illustrative numerical example we applied our method to a
      blood coagulation model which was shown to accurately capture the coagulation
      characteristics observed in experiments, and therefore opening a door for more
      detailed study of systems which are currently hard to study using particle
      tracing methods.

PMID- 20044091
TI  - Ultrasound-assisted extraction and derivatization of sterols and fatty alcohols
      from olive leaves and drupes prior to determination by gas chromatography-tandem
      mass spectrometry.
AB  - A method for simultaneous determination of sterols and fatty alcohols in olive
      leaves and drupes based on ultrasound-assisted extraction and derivatization
      prior to individual identification-quantitation by chromatographic separation and
      mass spectrometry detection (single ion monitoring mode) is reported here. The
      sample preparation procedure involves the following steps: (i) leaching of the
      raw material accelerated by ultrasound; (ii) saponification of the leachate, also
      accelerated by ultrasound, and separation of the unsaponifiable matter; (iii)
      cleaning of the extract by solid-phase extraction; (iv) silylation of the target
      analytes-also assisted by ultrasound; (v) injection into the gas chromatograph
      for identification-simultaneous quantitation of the two families of compounds.
      Individual separation-determination of the fatty alcohols and sterols provide
      limits of detection (LOD) in the range 9.8 x 10(-2) to 2 microg/l and 5.0-6.0
      microg/l, respectively. The LOQs range from 0.3 to 0.9 microg/l and 17.0 to 21.0
      microg/l, and the linear dynamic ranges are between LOQ and 25.0 microg/ml. The
      between-day precision, expressed as relative standard deviation (RSD), ranges
      between 3.6 and 6.1% and the within-laboratory reproducibility, also expressed as
      RSD, between 6.4 and 9.2%. Within the study of the metabolomic profile of the
      unsaponifiable fraction in olive tree, the method has been applied to the
      determination of the target analytes in different varieties of olive trees
      cultivated in the same zone, so that differences in this unsaponifiable fraction
      can be attributed to characteristics of the target varieties. As compared with
      its European Union counterpart, the method is endowed with similar analytical
      characteristics and drastic shortening of the operational time.

PMID- 20044093
TI  - Efficiency of the same neat silica column in hydrophilic interaction
      chromatography and per aqueous liquid chromatography.
AB  - The dependencies on the mobile phase flow velocity of the efficiency of a column
      packed with shell particles of neat porous silica (Halo) was measured under two
      different sets of experimental conditions. These conditions corresponded to the
      retention mechanisms of per aqueous liquid chromatography (PALC) at low
      acetonitrile concentrations and of hydrophilic interaction chromatography (HILIC)
      at high acetonitrile concentrations. The results are compared. Small amounts of a
      diluted solution of caffeine were injected in order to record the chromatograms
      under strictly linear conditions. These efficiencies were measured in both water
      rich (PALC retention mechanism) and acetonitrile-rich (HILIC mechanism) mobile
      phases for the same retention factors, between 0.25 and 2.5. The mobile phases
      were mixtures of acetonitrile and water containing neither supporting salt nor
      buffer component. At low retention factors, the efficiency of caffeine is better
      in the PALC than in the HILIC mode. For k(')=0.5, the minimum reduced height
      equivalent to a theoretical plate (HETP) is close to 2.5 in PALC while it exceeds
      5 in HILIC. The converse is true for high retention factors. For k(')>2.5, the
      HETP is lower in HILIC than in PALC, because the major contribution to band
      broadening and peak tailing in this latter mode originates from the heterogeneous
      thermodynamics of retention and eventually restricts column performance in PALC.
      Most interestingly, the reduced HETP measured in HILIC for caffeine never falls
      below 4. This suggests that the mass transfer of caffeine between the multilayer
      adsorbed phase (due to the interactions of the strong solvent and the silanol
      groups) and the acetonitrile-rich bulk eluent is slow.

PMID- 20044092
TI  - Determination of water pollutants by direct-immersion solid-phase microextraction
      using polymeric ionic liquid coatings.
AB  - The determination of a group of eighteen pollutants in waters, including
      polycyclic aromatic hydrocarbons and substituted phenols, is conducted in direct
      immersion solid-phase microextraction (SPME) using the polymeric ionic liquid
      (PIL) poly(1-vinyl-3-hexadecylimidazolium) bis[(trifluoromethyl)sulfonyl]imide as
      a novel coating material. The performance of the PIL fiber coating in the
      developed IL-SPME-gas chromatography (GC)-mass spectrometry (MS) method is
      characterized by average relative recoveries of 92.5% for deionized waters and
      90.8% for well waters, average precision values (as relative standard deviations,
      RSD%) of 11% for deionized waters and 12% for well waters, using a spiked level
      of 5 ng mL(-1). The detection limits oscillate from 0.005 ng mL(-1) for
      fluoranthene to 4.4 ng mL(-1) for 4-chloro-3-methylphenol, when using an
      extraction time of 60 min with 20 mL of aqueous sample. The extraction
      capabilities of the PIL fiber have been compared with the commercial SPME
      coatings: polydimethylsyloxane (PDMS) 30 microm, PDMS 100 microm and polyacrylate
      (PA) 85 microm. The PIL fiber is superior to the PDMS 30 microm for all analytes
      studied. A qualitative study was also carried out to compare among the nature of
      the coating materials by normalizing the coating thickness. The PIL material was
      shown to be more efficient than the PDMS material for all analytes studied. The
      PIL coating was also adequate for nonpolar analytes whereas the PA material was
      more sensitive for polar compounds.

PMID- 20044094
TI  - Direct recovery of recombinant nucleocapsid protein of Nipah virus from
      unclarified Escherichia coli homogenate using hydrophobic interaction expanded
      bed adsorption chromatography.
AB  - A direct recovery of recombinant nucleocapsid protein of Nipah virus (NCp-NiV)
      from crude Escherichia coli (E. coli) homogenate was developed successfully using
      a hydrophobic interaction expanded bed adsorption chromatography (HI-EBAC). The
      nucleic acids co-released with the recombinant protein have increased the
      viscosity of the E. coli homogenate, thus affected the axial mixing in the EBAC
      column. Hence, DNase was added to reduce the viscosity of feedstock prior to its
      loading into the EBAC column packed with the hydrophobic interaction
      chromatography (HIC) adsorbent. The addition of glycerol to the washing buffer
      has reduced the volume of washing buffer applied, and thus reduced the loss of
      the NCp-NiV during the washing stage. The influences of flow velocity, degree of
      bed expansion and viscosity of mobile phase on the adsorption efficiency of HI
      EBAC were studied. The dynamic binding capacity at 10% breakthrough of 3.2mg/g
      adsorbent was achieved at a linear flow velocity of 178 cm/h, bed expansion of
      two and feedstock viscosity of 3.4 mPas. The adsorbed NCp-NiV was eluted with the
      buffer containing a step gradient of salt concentration. The purification of
      hydrophobic NCp-NiV using the HI-EBAC column has recovered 80% of NCp-NiV from
      unclarified E. coli homogenate with a purification factor of 12.5.

PMID- 20044095
TI  - Electric permittivity of concentrated suspensions of elongated goethite
      particles.
AB  - This paper describes an investigation on the electric permittivity of
      concentrated suspensions of non-spherical particles, specifically prolate
      spheroids. It is first discussed how the determination of the frequency (omega)
      dependence of the electric permittivity (a phenomenon traditionally known as LFDD
      or low-frequency dielectric dispersion) can provide ample information on the
      properties of the dispersed material (shape, size, state of aggregation,
      conductivity) and of its interface with the (typically aqueous) medium. The basic
      quantities are the strength and frequency dependence of the dipole moment induced
      by the applied field, and its dimensionless counterpart, the dipole coefficient,
      C(*)(omega). It is explicitly shown how the (complex) relative permittivity of
      the suspension, epsilon(r)(*)(omega), can be calculated from it. Two theoretical
      models on the polarizability of spheroidal colloidal particles will be used as
      theoretical starting point; one of them (Model I) explicitly considers two
      relaxations of the permittivity, each associated to one of the particle axes. The
      other (Model II) is a semi-analytical theory that yields an LFDD practically
      independent of the axial ratio of the particles. Both models are aimed to be used
      if the suspensions are dilute (low volume fraction of solids, phi), and here they
      are generalized to concentrated systems by means of a previously published
      approximate evaluation of the permittivity of concentrated suspensions.
      Experiments are performed in the 1 kHz-1 MHz frequency range on suspensions of
      elongated goethite particles; the effects of ionic strength, pH, and volume
      fraction are investigated, and the two models are fitted to the data. In reality,
      taking into account that the particles are non-uniformly charged (a fact that
      contributes to their instability), two zeta potentials (roughly representing the
      lateral surface and the tip of the spheroid) are used as parameters. The results
      indicate that, when experimental conditions are optimal (high ionic strength and
      low zeta potential), the suspensions do indeed display two relaxations, that we
      ascribe to the long axis (and to flocs likely present in suspension) and to the
      short one. The permittivity increases with ionic strength, a result found with
      other systems, and compatible with a zeta potential that, on the average,
      decreases with ionic strength, an equally well known result, consequence of
      electric double layer compression. Another reasonable finding is the increase of
      estimated average dimensions and the decrease of electrokinetic potentials when
      the pH is close to the isoelectric point of goethite (around pH 9). The increase
      in volume fraction, finally, produces an overall increase in the permittivity,
      and the approximate model used for the evaluation of volume fraction variations
      can describe properly these effects, with basically constant zeta potentials and
      dimensions.

PMID- 20044096
TI  - Dissolution of anisotropic colloidal mineral particles: evidence for basal
      surface reactivity of nontronite.
AB  - Anisotropic textural and crystallographic properties of phyllosilicate particles
      often influence the mineral weathering rate. The purpose of this study was to
      investigate how the changes in mineral surfaces (basal vs. edge) as a result of
      changes in crystal size control the dissolution of the mineral. Different nano
      size fractions of Na-exchanged nontronites (NAu2 and NAu1) were immobilized in a
      silica gel and then incubated under acidic conditions using HNO(3) at 28 degrees
      C for 5 days. For each sample, the dissolution behavior was analyzed by measuring
      the amount of iron released from the mineral lattice. The results showed that for
      a given pH, a decrease in particle size significantly increased NAu2 and NAu1
      dissolution. At pH 1.5, 7.2% of the total iron of the highest size sample of NAu2
      was released in solution whereas this proportion increased up to 25% for the
      smallest size fraction. The percentage of total iron extracted from NAu1 at the
      same pH (1.5) was less important: 3.5% and 6.5% for higher and smaller size
      fractions, respectively. The observed increase in dissolution was not directly
      correlated to the increase in the amount of edge faces, suggesting that all
      mineral surfaces contributed to mineral dissolution. In the present case this may
      be related to the fact that 8% and 2% of total iron of NAu2 and NAu1,
      respectively, are located in the tetrahedral sheet. In conclusion, the basal
      surface of nontronites plays an important role in the weathering process.

PMID- 20044097
TI  - Structures of D2 layers on LiF(001).
AB  - Classical Monte Carlo (MC) simulations of D(2) molecules physisorbed on LiF(001)
      surfaces are reported and show a series of interesting commensurate structure
      forms, viz., p(2x2) -->p(8x2) -->p(4x2), with coverages Theta=0.5, 0.625, and
      0.75, respectively, and are stable up to 8 K. These structures are consistent
      with recent helium atom scattering (HAS) results (the p(4x2) is not observed) in
      terms of coverage and stability, but disagree in terms of symmetry. The p(2x2)
      structure contains two D(2) molecules per unit cell, with each molecule lying
      parallel to the plane of the surface directly above every other cationic site.
      For the p(4x2) structure, there are two kinds of adsorption sites: a parallel
      site, as in the case of p(2x2), and a tilted site, where the D(2) molecules sit
      between cationic and anionic sites with the molecular axis directed toward the
      anionic site, with a tilt angle of theta approximately 63 degrees. Perturbation
      theory calculations show that the adsorbed D(2) molecules are azimuthally
      delocalized and hence the structures are indeed c-type. Our calculations also
      indicate that o-D(2) and helicoptering p-D(2) species prefer cationic sites,
      compared to cartwheeling p-D(2) species.

PMID- 20044098
TI  - Prefrontal oxygenation during working memory in ADHD.
AB  - OBJECTIVES: Deficits in working memory have been repeatedly found on a
      behavioural level in children with attention-deficit/hyperactivity disorder
      (ADHD). Functional brain imaging studies have revealed evidence for alterations
      in the prefrontal cortex associated with working memory. So far it remains
      unresolved whether object (OWM) and spatial visual working memory (SWM) are
      distinctly impaired in ADHD. We investigated this issue with the fist multi
      channel functional near-infrared spectroscopy study of children with ADHD.
      METHOD: We investigated 19 children with ADHD combined type (DSM-IV) and 19
      controls matched for age (8-15years), sex, handedness, and intelligence during a
      working memory task assessing OWM and SWM separately, and a control condition
      (CON). Prefrontal brain activity was measured by concentration changes of
      oxygenated haemoglobin. RESULTS: Working memory performance showed significant
      differences for conditions (OWM>SWM>CON), but no differences between groups.
      Cortical prefrontal activation was significantly higher for OWM and SWM in
      contrast to CON, again with no differences between groups. CONCLUSIONS: We found
      no indication for an altered prefrontal processing during OWM and SWM tasks in
      ADHD children compared to controls. Reviewing the existing imaging literature on
      working memory in ADHD and considering the present data, we discuss possible
      confounding factors relevant for brain activity in previous, the current, and
      future investigations. Thus, it is of high importance to capture developmental
      trajectories, task specific discrepancies, and effects of permanent medication
      intake in future studies.

PMID- 20044099
TI  - Relationship of metal content and bioavailability with benthic macrofauna in
      Camamu Bay (Bahia, Brazil).
AB  - Camamu Bay (Bahia, Brazil) is an Environmental Protected Area with mangroves of
      economic and ecological importance. The objective of this study was to elucidate,
      through the distribution of the benthic macrofauna and its relationships with
      trace metals and bioavailabilty, if the current quality of the mangrove sediments
      of Camamu Bay is acceptable for the protection of aquatic life. Seven sampling
      stations were selected as representative of the meso-littoral region of Camamu
      Bay. It was found 581 macrobenthic organisms distributed in 38 species. The
      highest values of metals occurred at stations located in areas that influenced by
      barite extraction, while the lowest concentrations were found in areas with
      relatively lower anthropogenic influence. Analysis of acid volatile sulphide and
      simultaneously extracted metals showed the occurrence of the ratio SEM/AVS >1,
      indicative of possible bioavailability of metals, at only one station. The
      results suggested that Camamu Bay is a nearly pristine area.

PMID- 20044100
TI  - [Community-acquired pneumonia: prognosis-related decisions].

PMID- 20044101
TI  - [Ethics on genetic research (1). Pharmacogenetic studies].

PMID- 20044102
TI  - [Pulmonary sarcoidosis].

PMID- 20044103
TI  - [Analysis of Spanish research about neck and back complaints (1992-2006)].

PMID- 20044104
TI  - [Late pneumopericardium after pericardiocentesis].

PMID- 20044105
TI  - [Risk factors for extended espectrum beta-lactamase producer E.coli bacteremia
      from urinary origin].
AB  - BACKGROUND AND OBJECTIVE: Although risk factors for extended spectrum beta
      lactamase E. coli (EBLE) infection have been explored, specific risk factors for
      bacteremic urinary tract infection by EBLE have been hardly analyzed. PATIENTS
      AND METHODS: We collected data from all patients with bacteremic urinary tract
      infection by E. coli attended in our hospital during 2006. Logistic regression
      was performed to explore predictors for EBLE bloodstream infection in this group
      of patients. RESULTS: EBLE was present in 19 cases (17,9%) out of 106 bacteraemia
      from urinary origin. Patients with bloodstream infection by EBLE were male,
      older, demented, living in a nursing home, with previous urologic diseases and
      urologic manipulation, with a higher percentage of previous urinary tract
      infection, previous antibiotic use, more frequent nosocomial infection, and
      hospital admission in the previous month. In the logistic regression analysis,
      only previous urologic diseases (OR 13,9; IC95% 2,5-78,2) and living in a nursing
      home (OR 6,5; IC95% 1,4-0,9) were associated with EBLE bacteremic urinary tract
      infection. CONCLUSIONS: Previous urologic disease and living in a nursing home
      are independent risk factors for EBLE bacteremic urinary tract infection.

PMID- 20044106
TI  - [Albuminuria as a prognostic marker in heart failure].

PMID- 20044107
TI  - [Chediak-Higashi syndrome].

PMID- 20044108
TI  - [Ethics on genetic research (2). Genetic susceptibility studies].

PMID- 20044109
TI  - [Relation between blood pressure and joint hypermobility].

PMID- 20044110
TI  - [Cystatin C: a protein for heart failure].
AB  - Cystatin C (CysC) is an antiprotease useful for measuring kidney function. Beyond
      such property, it carries significant prognostic information in several fields of
      cardiovascular diseases. We review data that support CysC as a prognostic factor
      in cardiovascular diseases among healthy elderly, hypertensive and heart failure
      patients. In addition, it has been speculated that CysC may be an early marker of
      ventricular remodelling, primarily involved in its pathogenesis, as a local
      antiprotease. Its role in physiopathology and clinical issues of cardiovascular
      pathology is yet to be elucidated.

PMID- 20044112
TI  - [Hypocalcaemia: an unusual and potentially reversible cause of dilated
      cardiomyopathy].

PMID- 20044111
TI  - [The role of iron in the interaction between host and pathogen].
AB  - Iron is essential for both pathogenic microbes and their host. Iron status may
      influence the occurrence and outcome of infections. For many microorganisms, iron
      is essential for growth, survival, and synthesis of virulence factors. However,
      because circulating iron is mostly transported bound to proteins and the level of
      free serum iron is therefore very low, some pathogens have developed complex
      systems to acquire iron efficiently. Understanding these systems is essential in
      the design of pharmaceutical agents and vaccines targeting pathogens with iron
      linked virulence. In this review, we examine current data on the role of iron in
      the struggle between host and pathogen to regulate levels of this essential
      element. We hope that, in the near future, treatments aimed at reducing iron
      overload will improve the response to current therapies, and help control
      infection.

PMID- 20044113
TI  - Preliminary report: homeostasis model assessment of insulin resistance, an
      indicator of insulin resistance, is strongly related to serum insulin: practical
      data presentation and the mathematical basis.
AB  - The homeostasis model assessment for insulin resistance (HOMA-R) is frequently
      used as an indicator of insulin resistance. The purpose of this study was to
      clarify the advantage of HOMA-R as an indicator of insulin resistance. A
      population of 3008 Japanese male workers (34 to 64 years old), who have no
      history of diabetes mellitus, hypertension, dyslipidemia, hyperuricemia, coronary
      and/or cerebrovascular disease and their fasting plasma glucose were under 140
      mg/dL. The Spearman's rank correlation coefficient between HOMA-R and the serum
      insulin was 0.982. Although HOMA-R is also regulated by the plasma glucose,
      insulin and plasma glucose are not independent. The lower and upper 2.5%ile data
      of plasma glucose were prepared, which were used for mathematical basis of strong
      correlation between HOMA-R and serum insulin. Subjects with higher insulin had
      higher plasma glucose, which was resulted in higher HOMA-R. In the same manner,
      HOMA-R would become lower in the area of lower insulin levels. As two lines of
      the lower and upper 2.5%ile data of plasma glucose exists near, the correlation
      between HOMA-R and serum insulin became very strong. Although HOMA-R is a popular
      indicator of insulin resistance, we recommend that HOMA-R could be substituted
      simply by serum insulin. This may be valid in the general population with no
      remakable medical condition.

PMID- 20044114
TI  - [Usefulness of contrast-enhanced ultrasonography in daily clinical practice: a
      multicenter study in Spain].
AB  - OBJECTIVES: We aimed to determine whether the use of ultrasonographic contrast
      agents improves the diagnostic performance of ultrasonography (US). MATERIAL AND
      METHODS: We carried out a prospective multicenter study in 42 hospitals. We
      included 1786 patients with inconclusive US; 84.9% of the inconclusive studies
      were abdominal US (including studies of the liver, kidneys, spleen, and other
      sites), 6.2% were studies of the peripheral vessels, 4.3% were breast studies,
      and 4.6% were other studies. We evaluated the type of contrast-enhanced US (color
      Doppler or contrast-specific method), type of contrast agent, dose and number of
      doses, and type of administration (bolus or infusion). We evaluated whether the
      findings at contrast-enhanced US improved the diagnostic performance of
      unenhanced US and whether they enabled a conclusive diagnosis to be reached.
      RESULTS: The contrast agent SonoVue was used in 99.9% of the studies; a single
      dose of contrast agent was used in 84.8%, and the contrast agent was administered
      in bolus in 98.5%. Contrast-enhanced US improved the diagnostic performance in
      91.6% of cases and enabled the conclusive diagnosis in 69.2%. The best diagnostic
      performance was obtained in the supraaortic trunks, where a definitive diagnosis
      was reached in 95.4% of cases, followed by the abdominal area, with a conclusive
      diagnosis in 72.6% of cases. CONCLUSIONS: The use of contrast-enhanced US
      significantly improved the diagnostic performance of US and enabled a conclusive
      diagnosis in most cases.

PMID- 20044115
TI  - Prevalence and incidence of bovine trypanosomosis in an agro-pastoral area of
      southwestern Burkina Faso.
AB  - The present study was conducted to determine the prevalence and incidence of
      trypanosomosis and to investigate some factors influencing them in an agro
      pastoral area of southwestern Burkina Faso. A total of 363 crossbred cattle
      (Baoule-zebu peul), which were bred under natural trypanosomosis challenge, were
      monitored monthly for parasitaemia, packed cell volume (PCV) and serological
      analyses over 2years. The parasitological prevalence estimated at the beginning
      of the survey using the buffy coat technique (BCT) was 7.54%. As much as 66.7% of
      all trypanosome infections were due to Trypanosoma vivax, 23.8% due to
      Trypanosoma congolense and 9.5% due to T. vivax/T. congolense mixed infections.
      The monthly serological incidence varied from 0.29% to 19.29%. The season was the
      most important factor influencing the serological prevalence and incidence and
      the animal PCV. The dry hot season is associated with increasing seroprevalences
      and incidences and consequently a decreasing average of PCV. In addition, an
      important spatial heterogeneity was observed.

PMID- 20044116
TI  - [Diagnostic procedure of limb girdle muscular dystrophies 2A or calpainopathies:
      French cohort from a neuromuscular center (Bordeaux)].
AB  - BACKGROUND: Limb girdle muscular dystrophies are rare genetic diseases. Despite
      constant progress in genetics and biochemistry, the pathogenic mechanisms are not
      completely understood. Calpainopathy (LGMD2A) has been reported to be the most
      frequent autosomal recessive form of muscular dystrophy in several populations.
      Point mutations in CAPN3 are difficult to identify and the analysis is long and
      costly. The use of western blot does not seem to provide the expected sensitivity
      and specificity. PATIENTS AND METHOD: We studied all the patients diagnosed in
      the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in
      order to establish the appropriate diagnostic approach (inclusion criteria:
      muscular biopsy with calpain 3 western blot study, two mutations in CAPN3).
      Patients with highly suspected calpainopathy (same criteria with only one
      mutation) were also analyzed. RESULTS: Our 13 patients belonged to 10 different
      families. Four patients had a normal western blot for calpain (WBn). We found
      high phenotypic variability with frequent atypical signs. The WBn group had less
      severe disease (a statistically significant later age of onset, a tendency toward
      lower CK levels and a slower disease course). We extended this comparison to the
      single mutation patients and we found the same results. CONCLUSION: Considering
      the lack of sensitivity of western blot protein analysis in LGMD2A, a normal
      western blot for calpain should not halt the genetic analysis. The western blot
      result seems to have prognostic value. A normal western blot may help genetic
      testing by highlighting some mutational hot spots in the CAPN3 gene.

PMID- 20044117
TI  - Simultaneous counter-flow of chlorinated volatile organic compounds across the
      saturated-unsaturated interface region of an aquifer.
AB  - Concentrations of chlorinated volatile organic compounds (Cl-VOCs) at the
      saturated-unsaturated interface region (SUIR; depth of approximately 18m) of a
      sandy phreatic aquifer were measured in two monitoring wells located 25m apart.
      The concentrations of the Cl-VOCs obtained above and below the water table along
      a 413-day period are interpreted to depict variable, simultaneous and independent
      movement of trichlorothene, tetrachloroethene, 1,1-dichloroethene, cis-1,2
      dichloroethene, 1,1,1-trichloroethane, chloroform and 1,1-dichloroethane vapors
      in opposite directions across the SUIR.

PMID- 20044118
TI  - Short- and long-term temperature effects on aerobic polyhydroxybutyrate producing
      mixed cultures.
AB  - Short- and long-term temperature effects on polyhydroxybutyrate (PHB) producing
      mixed cultures enriched in feast-famine sequencing batch reactors (SBRs) were
      investigated in a temperature range of 15-35 degrees C and 15-30 degrees C,
      respectively. After short-term temperature changes (i.e. 1 cycle) from the steady
      state temperature of 20 degrees C, reaction rate changes in the famine phase
      could be described over the whole temperature range with the Arrhenius equation
      with one temperature coefficient. For the feast phase different temperature
      coefficients were identified for acetate uptake, PHB production and growth. These
      were only valid for temperatures 5 degrees C higher or lower than the steady
      state temperature. Long-term temperature changes (i.e. new steady states)
      influenced not only the reaction rates but also the selective pressure in the
      SBR. At higher temperatures (30 degrees C) the SBR feast phase was short and the
      rates of acetate uptake and PHB storage were very high. This culture was
      characterized by a storage strategy with high yields of PHB and low yields of
      biomass in the feast phase. The PHB storage capacity of this culture was 84 wt%
      as evaluated in fed-batch experiments. At lower temperatures (15 degrees C) the
      feast phase was longer due to a lower rate of acetate uptake and the culture
      followed a strategy of direct growth on acetate rather than on PHB. This culture
      had a low maximal PHB storage capacity (about 35 wt%). The SBR culture enriched
      at 20 degrees C was able to store up to about 70 wt% PHB. The temperature at
      which fed-batch experiments were conducted did not influence the maximal PHB
      storage capacity. The SBR temperature was found to be an important factor to
      consider when designing a mixed culture PHB production process.

PMID- 20044119
TI  - Evaluating operating conditions for outcompeting nitrite oxidizers and
      maintaining partial nitrification in biofilm systems using biofilm modeling and
      Monte Carlo filtering.
AB  - In practice, partial nitrification to nitrite in biofilms has been achieved with
      a range of different operating conditions, but mechanisms resulting in reliable
      partial nitrification in biofilms are not well understood. In this study,
      mathematical biofilm modeling combined with Monte Carlo filtering was used to
      evaluate operating conditions that (1) lead to outcompetition of nitrite
      oxidizers from the biofilm, and (2) allow to maintain partial nitrification
      during long-term operation. Competition for oxygen was found to be the main
      mechanism for displacing nitrite oxidizers from the biofilm, and preventing re
      growth of nitrite oxidizers in the long-term. To maintain partial nitrification
      in the model, a larger oxygen affinity (i.e., smaller half saturation constant)
      for ammonium oxidizers compared to nitrite oxidizers was required, while the
      difference in maximum growth rate was not important for competition under steady
      state conditions. Thus, mechanisms for washout of nitrite oxidizing bacteria from
      biofilms are different from suspended cultures where the difference in maximum
      growth rate is a key mechanism. Inhibition of nitrite oxidizers by free ammonia
      was not required to outcompete nitrite oxidizers from the biofilm, and to
      maintain partial nitrification to nitrite. But inhibition by free ammonia
      resulted in faster washout of nitrite oxidizers.

PMID- 20044120
TI  - Extraction of PCBs and water from river sediment using liquefied dimethyl ether
      as an extractant.
AB  - We investigated whether polychlorinated biphenyls (PCBs) and water could be
      simultaneously removed from river sediment by solvent extraction using liquefied
      dimethyl ether (DME) as the extractant. DME exists in a gaseous state at normal
      temperature and pressure and can dissolve organic substances and some amount of
      water; therefore, liquefied DME under moderate pressure (0.6-0.8 MPa) at room
      temperature can be effectively used to extract PCBs and water from contaminated
      sediment, and it can be recovered from the extract and reused easily. First, we
      evaluated the PCB and water extraction characteristics of DME from contaminated
      sediment. We found that 99% of PCBs and 97% of water were simultaneously
      extracted from the sediment using liquefied DME at an extraction time of 4320 s
      and a liquefied DME/sediment ratio of 60 mL g(-1). The extraction rate of PCBs
      and water was expressed in terms of a pseudo-first-order reaction rate. Second,
      we estimated the amount of DME that was recovered after extraction. We found that
      91-92% of DME could be recovered. In other words, approximately 5-10% of DME was
      lost during extraction and recovery. It is necessary to optimize this process in
      order to recover DME efficiently. The extraction efficiency of the recovered DME
      is similar to that of the pure DME. From the results, we conclude that solvent
      extraction using liquefied DME is suitable for extracting PCBs and water from
      contaminated sediment.

PMID- 20044121
TI  - The responses of Arabidopsis thaliana to cadmium exposure explored via metabolite
      profiling.
AB  - The metabolic responses of Arabidopsis thaliana to cadmium exposure was
      characterized in this study. A. thaliana was cultivated in medium contaminated
      with different cadmium concentrations (0, 5 and 50microM, respectively) for
      2weeks. Metabolite analyses were performed using gas chromatography-mass
      spectrometry. More than 80 metabolites characterized by retention time indices
      and specific mass fragments were identified. The levels of carbohydrates, organic
      acids, amino acids, and other stress-responsive metabolites changed under cadmium
      stress. Treated plants showed increased levels of Ala, beta-ala, Pro, Ser,
      putrescine, Suc and other metabolites with compatible solute-like properties,
      notably 4-aminobutyric acid, glycerol, raffinose and trehalose, compared to
      control (untreated) plants. Studies indicated that concentrations of antioxidants
      (alfa-tocopherol, campesterol, beta-sitosterol and isoflavone) also increased
      significantly. These results confirm the important role of antioxidant defences
      in the mechanisms of plant-resistance to cadmium stress. Our results suggested
      that metabolic profiling is a powerful tool that can rapidly classify
      environmentally modified plants and simplify the process of cadmium-stress
      responses. These data will be helpful for better understanding of mechanisms of
      plant adaptation to cadmium stress at the metabolite level.

PMID- 20044123
TI  - Occurrence and assessment of perfluorinated chemicals in wild fish from Northern
      Germany.
AB  - Residues of the perfluorinated chemicals perfluorooctanesulfonate (PFOS) and
      perfluorooctanoicacid (PFOA) were investigated in wild fish caught from different
      German waters including the North and the Baltic Sea, Lake Storkow in
      Brandenburg, several rivers in Lower Saxony, and rivers and lakes in the city of
      Berlin. The sample locations represent waters with no, low, medium and high
      portions of treated municipal sewage discharges. The investigated fish filet
      samples included 51 wild eels, 44 bream, 5 herring, 5 mackerel, 3 carp and 4
      trout. PFOA was not found in any of the investigated samples above the limit of
      quantitation of 0.27 microgkg(-1) fresh weight (fw.), whereas PFOS was detected
      with concentrations up to 225 microgkg(-1)fw. PFOS was found in the filet samples
      caught from densely populated regions at levels between 8.2 and 225 microgkg(
      1)fw. In samples from marine or remote locations, PFOS was not detected or only
      detected at levels up to 50.8 microgkg(-1)fw. To date, a tolerable daily intake
      (TDI) for PFOS and PFOA has or could not finally be fixed by any official
      national or international organization. A provisional TDI of 150 microgkg(-1)
      body weight per day has, however, been proposed by the European Food Safety
      Authority to be used for a provisional risk assessment. Thus, the detected
      residues of PFOS found in 33 out of 112 examined fish samples might be classified
      as potential risks for the health of consumers with elevated fish consumption.

PMID- 20044122
TI  - Effects of 1-methyl-3-octylimidazolium bromide on the anti-oxidant system of
      earthworm.
AB  - The activity changes of anti-oxidant enzymes and the levels of glutathione and
      malondialdehyde were determined when Eisenia foetida were exposed to different
      concentrations of 1-methyl-3-octylimidazolium bromide for 14d. The results showed
      catalase activity in all treatment groups was elevated significantly after 1d of
      exposure, and superoxide dismutase activity in higher-dosage groups (120 and
      160mgkg(-1)) was increased at 3d post-exposure. On the 7thd, the activity of
      glutathione-S-transferase in the 20 and 40mgkg(-1) dosage groups was inhibited
      while increased in the 80 and 160mgkg(-1) groups compared with the control
      groups. During exposure, the level of intracellular glutathione in all treatment
      groups was much higher than that of the control groups. Changes in
      malondialdehyde indicate that [C(8)mim]Br may lead to cellular lipid peroxidation
      in earthworm. Our results suggest that exposure to [C(8)mim]Br induce the
      formation of reactive oxygen species in earthworms.

PMID- 20044124
TI  - Screening of chemicals with anti-estrogenic activity using in vitro and in vivo
      vitellogenin induction responses in zebrafish (Danio rerio).
AB  - Growing concern over possible adverse effects of endocrine-disrupting chemicals
      (EDCs) has driven the development of associated screening methods. The use of the
      vitellogenin (VTG) induction response in cultured teleost hepatocytes has been
      suggested as an in vitro screening assay for EDCs. However, current data do not
      sufficiently support this assay in the routine screening of chemicals. This study
      established and validated the use of primary cultured hepatocytes from zebrafish
      to screen chemicals for anti-estrogenic activities. Here we measured the
      transcript levels of selected hepatic estrogen-response genes, including vtg1,
      vtg2 and eralpha. Two model anti-estrogens, letrozole (LET), an aromatase
      inhibitor, and tamoxifen (TAM), a competitive estrogen receptor, were selected as
      representative chemicals. Additionally, comparisons between in vitro and in vivo
      assays were performed. As expected, there were concentration-dependent decreases
      for all three genes in the liver of female zebrafish exposed to LET in vivo for
      72h. Similar responses were observed in males. As for in vitro testing, no
      discernable alterations in the gene transcripts were found in hepatocytes from
      males or females. In the case of TAM, exposure for 72h caused transcriptional
      reduction of hepatic estrogen-response genes in females in vivo and in vitro. In
      males, low concentrations of TAM resulted in increased expression of genes, while
      the expression decreased slightly at higher concentrations. Since these
      observations were in agreement with the pharmaceutical properties of two tested
      chemicals, the primary hepatocyte culture could be a promising tool for screening
      suspected EDCs.

PMID- 20044125
TI  - Growth, development and sex ratios of Spotted Marsh Frog (Limnodynastes
      tasmaniensis) larvae exposed to atrazine and a herbicide mixture.
AB  - Exposures of Limnodynastes tasmaniensis tadpoles to atrazine (0.1, 1, 3 and
      30microgL(-1)), metolachlor (0.1, 1 and 10microgL(-1)) and thiobencarb (90, 180
      and 360microgL(-1)) from Gosner stage 28 to 42 under controlled laboratory
      conditions gave no significant effects on tadpole growth, development and sex
      ratios. A binary mixture of atrazine and thiobencarb as well as a ternary mixture
      of all three herbicides also had no significant effects on the developing larvae
      to show no evidence of interactive toxicity. Abnormal gonad morphology was
      observed on two occasions; both from 0.1microgL(-1) atrazine treatments with one
      tadpole observed with testicular ovarian follicles. The low frequencies of
      abnormal gonadal morphology and testicular ovarian follicles did not indicate a
      concentration associated response to herbicide exposure. No significantly
      unbalanced sex ratios were observed to suggest any evidence of chemically induced
      feminisation. These observations suggest that environmentally relevant
      concentrations of atrazine, metolachlor and thiobencarb do not present a
      significant threat to the normal development of L. tasmaniensis larvae in surface
      waters of irrigated agricultural areas.

PMID- 20044126
TI  - Surfactant properties and tetrachloroethene (PCE) solubilisation ability of humic
      acid-like substances extracted from maize plant and from organic wastes: a
      comparative study.
AB  - Humic acid-like substance (HA-like substance) extracted from maize plant residue
      at an yield of 81.1+/-4.9gkg(-1) of dry matter (dm) was tested for surfactant
      properties and ability to solubilise tetrachloroethene (PCE). Critical micelle
      concentration (CMC) of HA-like substance was detected to be 1986mgL(-1). Both, HA
      like substance composition and average molecular weight [MW] affected CMC and a
      multiple linear regression model was proposed: CMC=12246-56.19 alkyl-C - 0.532MW
      (R(2)=0.90; P<0.01, n=7) where CMC was given in mgL(-1), alkyl-C was the
      percentage of total C, and MW was given in Da. Maize-HA-like substance
      solubilised PCE at the rate of 0.05g of PCE for each gram of maize-HA-like
      substance, which was 3.6-9.6 times lower than the data obtained in our earlier
      work using HA extracted from organic wastes, but was higher than that obtained
      with commercial HA from leonardite. Taking into consideration the two-site model
      of solubilisation of PCE in surfactant (i.e., solute partitioning into the
      micellar hydrophobic core and dissolution and/or binding into the hydrophilic non
      ionic shell) and macromolecular composition of HA-like substance, the non-ionic
      hydrophile-alkyl lipophile balance was expected to control PCE solubilisation as
      the good multiple linear regression indicated: logK(dom)=-1.37+0.062 alkyl-C
      +0.055 O-alkyl-C (R(2)=0.93, P<0.05, n=6), where logK(dom) represents the micelle
      water partitioning of PCE (mLg(-1)) and alkyl-C and O-alkyl-C represent the
      content of these two kinds of C detected by CP MAS (13)C NMR (as % of the total
      C).

PMID- 20044127
TI  - Molar crown development in Australopithecus afarensis.

PMID- 20044129
TI  - Factors accounting for youth suicide attempt in Hong Kong: a model building.
AB  - This study aimed at proposing and testing a conceptual model of youth suicide
      attempt. We proposed a model that began with family factors such as a history of
      physical abuse and parental divorce/separation. Family relationship, presence of
      psychopathology, life stressors, and suicide ideation were postulated as
      mediators, leading to youth suicide attempt. The stepwise entry of the risk
      factors to a logistic regression model defined their proximity as related to
      suicide attempt. Path analysis further refined our proposed model of youth
      suicide attempt. Our originally proposed model was largely confirmed. The main
      revision was dropping parental divorce/separation as a risk factor in the model
      due to lack of significant contribution when examined alongside with other risk
      factors. This model was cross-validated by gender. This study moved research on
      youth suicide from identification of individual risk factors to model building,
      integrating separate findings of the past studies.

PMID- 20044128
TI  - Single agent carboplatin versus carboplatin plus pegylated liposomal doxorubicin
      in recurrent ovarian cancer: final survival results of a SWOG (S0200) phase 3
      randomized trial.
AB  - OBJECTIVES: Randomized phase 3 trials have demonstrated the utility of a regimen
      of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian
      cancer, and have provided provocative data suggesting a substantially lower risk
      of carboplatin-associated hypersensitivity if PDL is delivered in combination
      with the platinum agent. METHODS: To further examine both of these clinically
      relevant issues, the survival outcome (with longer follow-up) and
      hypersensitivity reaction profile of a previously reported phase 3 trial that
      compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30
      mg/m(2)) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG
      0200) were re-analyzed. RESULTS: In the limited number of patients (n=61) entered
      into this phase 3 study before closure by the SWOG Data Safety and Monitoring
      Committee due to insufficient accrual, there was an initially reported
      improvement in outcome associated with the combination regimen. With longer
      follow-up and additional events there is still a statistically-significant
      improved progression-free survival (median: 12 versus 8 months, p=0.02), but the
      previously observed impact of the two-drug regimen on overall survival is no
      longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity
      reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients
      (30%) of women randomized to single agent carboplatin experienced an allergic
      episode (p=0.0008), with 5 being >grade 2 in severity. CONCLUSION: Despite a
      favorable impact of carboplatin and PLD on progression-free survival in this
      trial, the effect on overall survival is not statistically significant. For
      currently unknown reasons, administering PLD with carboplatin appears to
      substantially reduce the incidence of platinum-associated hypersensitivity
      reactions.

PMID- 20044130
TI  - Wastewater discharge degrades coastal waters and reef communities in southern
      Thailand.
AB  - Runoff and sewage discharge from land developments can cause significant changes
      in water quality of coastal waters, resulting in coral degradation. Coastal
      waters around Phuket, Thailand are influenced by numerous sewage outfalls
      associated with rapid tourism development. Water quality and biological
      monitoring around the Phuket region was undertaken to quantify water quality and
      biotic characteristics at various distances from sewage outfalls. The surveys
      revealed strong gradients in water quality and biotic characteristics associated
      with tourism concentration levels as well as seasonal variability. Water and reef
      quality tended to decrease with increasing tourist intensity, but improved with
      increasing distance from sewage discharge within each of the three study
      locations. In addition, the effect of wastewater discharge was not localised
      around the source of pollution, but appeared to be transported to non-developed
      sites by currents, and exacerbated in the wet season.

PMID- 20044131
TI  - The efficacy of self-assembled cationic antimicrobial peptide nanoparticles
      against Cryptococcus neoformans for the treatment of meningitis.
AB  - Cationic antimicrobial peptides have received considerable interest as new
      therapeutics with the potential for treatment of multiple-drug resistant
      infections. We recently reported that cholesterol-conjugated G(3)R(6)TAT
      (CG(3)R(6)TAT) formed cationic nanoparticles via self-assembly, which
      demonstrated strong antimicrobial activities against various types of microbes in
      vitro. In this study, the possibility of using these nanoparticles for treatment
      of Cryptococcus neoformans (yeast)-induced brain infections was studied. The
      antimicrobial activity of the nanoparticles was tested against 12 clinical
      isolates of C. neoformans in comparison with conventional antifungal agents
      amphotericin B and fluconazole. Minimum inhibitory concentrations (MICs) of the
      nanoparticles were determined to be much lower than those of fluconazole in all
      the isolates, but slightly higher than those of amphotericin B in some isolates.
      At a concentration three times higher than the MIC, the nanoparticles completely
      sterilized C. neoformans after 3.5 h. Cell wall disruption and release of
      cytoplasmic content were observed under TEM. The biodistribution studies of FITC
      loaded nanoparticles in rabbits revealed that the nanoparticles were able to
      cross the blood-brain barrier (BBB). The efficacy of nanoparticles was further
      evaluated in a C. neoformans meningitis rabbit model. The nanoparticles crossed
      the BBB and suppressed the yeast growth in the brain tissues with similar
      efficiency as amphotericin B did. In addition, unlike amphotericin B, they
      neither caused significant damage to the liver and kidney functions nor
      interfered with the balance of electrolytes in the blood. CG(3)R(6)TAT
      nanoparticles can be a promising antimicrobial agent for treatment of brain
      infections caused by C. neoformans.

PMID- 20044132
TI  - Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery
      system intramuscularly administered in rats.
AB  - A hybrid, localized and release-controlled delivery system for bone growth
      factors consisting of a liposomal core incorporated into a shell of alternating
      layer-by-layer self-assembled natural polyelectrolytes has been formulated.
      Hydrophilic, monodisperse, spherical and stable cationic nanoparticles (< or =350
      nm) with an extended shelf-life resulted. Cytocompatibility was previously
      assayed with MC3T3-E1.4 mouse preosteoblasts showing no adverse effects on cell
      viability. In this study, the in vivo biocompatibility of unloaded and loaded
      nanoparticles with osteogenic protein-1 or OP-1 was investigated. Young male
      Wistar rats were injected intramuscularly and monitored over a period of 10 weeks
      for signs of inflammation and/or adverse reactions. Blood samples (600
      microL/collection) were withdrawn followed by hematological and biochemical
      analysis. Body weight changes over the treatment period were noted. Major organs
      were harvested, weighed and examined histologically for any pathological changes.
      Finally, the injection site was identified and examined immunohistochemically.
      Overall, all animals showed no obvious toxic health effects, immune responses
      and/or change in organ functions. This hybrid core-shell nanoparticulate delivery
      system localizes the effect of the released bioactive load within the site of
      injection in muscle with no significant tissue distress. Hence, a safe and
      promising carrier for therapeutic growth factors and possibly other biomolecules
      is presented.

PMID- 20044133
TI  - Biodistribution of gold nanoparticles and gene expression changes in the liver
      and spleen after intravenous administration in rats.
AB  - Biodistribution of gold nanoparticles (AuNPs) in more than 25 organs were
      examined on 1 day, 1 week, 1 month and 2 months after a single intravenous (i.v.)
      injection in rats. Au was rapidly and consistently accumulated in liver (49.4+/
      50.4-72.2+/-40.5 ng/g) and spleen (8.4+/-5.0-9.5+/-6.4 ng/g) throughout the
      entire timeframe of the study (2 months). Significant accumulation of Au in
      kidney (up to 5.5+/-2.5 ng/g) and testis (up to 0.6+/-0.1 ng/g) occurred from 1
      month post-injection when Au level in urine and feces decreased. Significant
      increase of Au in blood occurred 2 months after injection, coincident with the
      delayed accumulation in kidney. Au accumulation in lungs was found at 1 day post
      injection but decreased within a week. No accumulation of Au was found in the
      brain. Microarray results of liver and spleen point to significant effects on
      genes related to detoxification, lipid metabolism, cell cycle, defense response,
      and circadian rhythm. These results demonstrate that significant biodistribution
      of Au occurs in the body over 2 months after a single i.v. injection of AuNPs,
      accompanied by gene expression changes in target organs.

PMID- 20044134
TI  - The ability of a collagen/calcium phosphate scaffold to act as its own vector for
      gene delivery and to promote bone formation via transfection with VEGF(165).
AB  - Collagen/calcium phosphate scaffolds have been used for bone reconstruction due
      to their inherent similarities to the bone extracellular matrix. Calcium
      phosphate alone has also been used as a non-viral vector for gene delivery. The
      aim of this study was to determine the capability of a collagen/calcium phosphate
      scaffold to deliver naked plasmid DNA and mediate transfection in vivo. The
      second goal of the study was to deliver a plasmid encoding vascular endothelial
      growth factor(165) (pVEGF(165)) to promote angiogenesis, and hence bone
      formation, in a mouse intra-femoral model. The delivery of naked plasmid DNA
      resulted in a 7.6-fold increase in mRNA levels of beta-Galactosidase compared to
      the delivery of plasmid DNA complexed with a partially degraded PAMAM dendrimer
      (dPAMAM) in a subcutaneous murine model. When implanted in a muirne intra-femoral
      model, the delivery of pVEGF(165) resulted in a 2-fold increase in bone volume at
      the defect site relative to control scaffolds without pVEGF(165). It was
      concluded that a collagen/calcium phosphate scaffold can mediate transfection
      without the use of additional transfection vectors and can promote bone formation
      in a mouse model via the delivery of pVEGF(165).

PMID- 20044135
TI  - Transient in vitro epigenetic reprogramming of skin fibroblasts into multipotent
      cells.
AB  - Multipotent stem cells have the potential to establish a new field of promising
      regenerative medicine to treat tissue damage, genetic disorders, and degenerative
      diseases. However, limited resource of stem cells has turned to be an evitable
      obstacle in clinical applications. We utilized a simple in vitro epigenetic
      reprogramming approach to convert skin fibroblasts into multipotent cells. After
      transient reprogramming, stem cell markers, including Oct4 and Nanog, became
      activated in the treated cells. The reprogrammed cells were multipotent as
      demonstrated by their ability to differentiate into a variety of cells and to
      form teratomas. Genomic imprinting of insulin-like growth factor II (Igf2) and
      H19 was not affected by this short period of cell reprogramming. This study may
      provide an alternative strategy to efficiently generate patient-specific stem
      cells for basic and clinical research, solving major hurdles of virally-induced
      pluripotent stem (iPS) cells that entail the potential risks of mutation, gene
      instability, and malignancy.

PMID- 20044136
TI  - Mechanism of enzymatic degradation of beta-sheet crystals.
AB  - The anti-parallel beta pleated sheet is a fundamental secondary structure in
      proteins and a major component in silk fibers generated by silkworms and spiders,
      with a key role to stabilize these proteins via physical cross-links.
      Importantly, these beta-sheets are fully degradable and nontoxic structures in
      biology, in contrast for example to beta-amyloid structures formed in disease
      states. Thus, insight into mechanism of enzymatic degradation would be
      instructive as a route to elucidating differences among these stable yet
      different structural features in biological systems. We report on the mechanism
      of enzymatic degradation of anti-parallel beta pleated sheets with Bombyx mori
      silk structures, leading to fibrils and subsequently to nanofilaments (2nm
      thickness and 160nm length). These nanofilaments play a role as nucleators of the
      crystalline regions, an important feature of the system that can be exploited to
      design silk-based biomaterials with predictable biodegradability and mechanical
      properties. The potential toxicity of degradation products from these proteolytic
      enzymes was also assessed in vitro and no cell toxicity found in vitro for the
      protease found in vivo in the human body. The degradation mechanism of beta-sheet
      silk crystals provides additional insight into the significant differences in
      biological impact between the anti-parallel beta-sheet silk biomaterials reported
      in this work vs. amyloid structures in disease states, adding to prior
      descriptions of chemical and structural differences that are more extensively
      documented.

PMID- 20044137
TI  - The paradox of caspase 8 in human villous trophoblast fusion.
AB  - Differentiation and subsequent fusion of villous cytotrophoblasts with the
      overlying syncytiotrophoblast is an essential process for growth and maintenance
      of the villous trophoblast layer in the human placenta. The understanding of
      intrinsic mechanisms behind this process is in its infancy, while the list of
      suggested factors, involved in intercellular fusion of trophoblasts, rapidly
      increased in the recent past and promises progress on this issue. The early
      stages of the apoptosis cascade, in particular caspase 8, was suggested to
      trigger differentiation of cytotrophoblasts, priming them for upcoming fusion.
      This may sound paradoxical, especially for those who still associate caspase
      activity with apoptosis only. Here, we summarize data on caspase 8 in the villous
      trophoblast layer, with a specific focus on localization of pro- and active
      forms, the sites of its activation and deactivation, and its role and regulation
      during fusion. Moreover, we revisit the knowledge on fusogens in the villous
      trophoblast, compare in vitro models for trophoblast fusion and discuss methods
      to quantify fusion.

PMID- 20044138
TI  - Modulation of feeding and locomotion through mu and delta opioid receptor
      signaling in the nucleus accumbens.
AB  - Opioid signaling has been strongly implicated in driving palatable food
      consumption. The nucleus accumbens (NAcc) is one important site of this effect;
      hyperphagia elicited by administration of exogenous mu opioid receptor (MOR)
      ligands in this brain region has been well documented. However, the role that
      endogenous opioid ligands in the NAcc play in controlling food intake remains
      poorly understood. Enkephalins, which signal through both the MOR and delta
      opioid receptor (DOR), are highly expressed within a subset of NAcc neurons, and
      have been shown to be sensitive to manipulations of diet and motivation. To
      investigate a potential role for these signaling molecules in regulating
      palatability-driven consumption, we measured high fat chow intake in rats
      following a series of pharmacological manipulations of NAcc opioid signaling.
      NAcc infusion of the MOR agonist [D-Ala2, N-MePHe4, Gly-ol]-enkephalin (DAMGO)
      robustly increased palatable food intake, as has previously been demonstrated. In
      contrast, neither infusion of Met-enkephalin, its synthetic analogue [D-Ala2] Met
      enkephalin (DALA) nor the DOR-specific ligand [D-Pen2, Pen5]-enkephalin (DPDPE)
      had significant effects on food intake. However, when administered in combination
      with DAMGO, DPDPE significantly suppressed the magnitude of DAMGO-evoked feeding.
      Further analysis of DPDPE effects revealed that the drug strongly increased
      locomotor activity. Suppressive effects on feeding, then, may have occurred
      through competition between feeding and locomotion for behavioral expression.

PMID- 20044140
TI  - Interleukin-1 Receptor-Associated Kinase-1 (IRAK-1) functionally associates with
      PKCepsilon and VASP in the regulation of macrophage migration.
AB  - Macrophage migration is mediated by complex cellular signaling processes and
      cytoskeleton re-arrangement. In particular, recent advances indicate that the
      innate immunity signaling process plays a key role in the regulation of
      macrophage migration. In this report, we have provided evidence demonstrating the
      involvement of a key innate immunity signaling kinase, Interleukin-1 Receptor
      Associated Kinase-1 (IRAK-1) as a critical modulator of macrophage migration.
      Macrophage migration induced by phorbol 12-myristate 13-acetate (PMA) is
      significantly attenuated in IRAK-1(-/-) macrophages as compared to wild type
      macrophages. Mechanistically, we demonstrated that IRAK-1 works downstream of
      PKCepsilon and upstream of VASP, a member of Ena/VASP family proteins. IRAK-1
      forms a close complex with PKCepsilon as well as VASP, and participates in PMA
      induced phosphorylation of VASP. Notably, IRAK-1 contains a novel EVH1 domain
      binding motif (L(167)WPPPP) within its N-terminus, which is responsible for its
      interaction with VASP. The mutant IRAK-1 (L167A/W168A) fails to associate with
      VASP. Our findings provide a novel facet regarding the molecular signaling
      process regulating macrophage migration.

PMID- 20044139
TI  - CHOP-independent apoptosis and pathway-selective induction of the UPR in
      developing plasma cells.
AB  - Upon antigen stimulation, B lymphocytes differentiate into antibody secreting
      cells (ASC), most of which undergo apoptosis after a few days of intense Ig
      production. Differentiation entails expansion of the endoplasmic reticulum (ER)
      and requires XBP1 but not other elements of the unfolded protein response, like
      PERK. Moreover, normal and malignant ASC are exquisitely sensitive to proteasome
      inhibitors, but the underlying mechanisms are poorly understood. Here we analyze
      the role of C/EBP homologous protein (CHOP), a transcription factor mediating
      apoptosis in many cell types that experience high levels of ER stress. CHOP is
      transiently induced early upon B cell stimulation: covalent IgM aggregates form
      more readily and IgM secretion is slower in chop(-/-) cells. Despite these subtle
      changes, ASC differentiation and lifespan are normal in chop(-/-) mice. Unlike
      fibroblasts and other cell types, chop(-/-) ASC are equally or slightly more
      sensitive to proteasome inhibitors and ER stressors, implying tissue-specific
      roles for CHOP in differentiation and stress.

PMID- 20044141
TI  - Impact of coagulation-balance gene predictors on efficacy of photodynamic therapy
      for choroidal neovascularization in pathologic myopia.
AB  - PURPOSE: To investigate whether different coagulation-balance genetic backgrounds
      might explain the variable clinical outcomes detected, after a single
      photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with
      subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM).
      DESIGN: Retrospective, consecutive, nonrandomized, interventional cases series.
      PARTICIPANTS: Two hundred thirty-four patients exclusively treated with
      standardized PDT-V for the presence of PM-related classic CNV. METHODS: The
      enrolled patients were subdivided as responders or nonresponders based on CNV
      responsiveness to the first PDT-V over a 3-month period. Three common gene
      polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T,
      and methionine synthase reductase A66G, were genotyped by polymerase chain
      reaction in each patient. MAIN OUTCOME MEASURES: The measures of CNV
      responsiveness to PDT-V were the changes, respect to baseline, of fluorescein
      angiography CNV leakage, greatest linear dimension, and area of the lesion.
      Logistic regression analyses were performed to explore the predictive role of
      phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and
      genotypic (all the mentioned mutations) variables regarding PDT-V efficacy.
      RESULTS: Responders to PDT-V were overrepresented within carriers of
      methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95%
      confidence interval [CI], 1.8-5.4; P = 0.001) and, to a minor extent, among
      patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6-88.0; P =
      0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR,
      0.73; 95% CI, 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT
      genotypes (OR, 0.19; 95% CI, 0.11-0.35; P = 0.0001). All the other considered
      predictive factors did not significantly influence the CNV responsiveness to PDT
      V. CONCLUSIONS: These findings document the presence of pharmacogenetic
      correlations between common coagulation-balance gene polymorphisms and different
      CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.

PMID- 20044142
TI  - Divalproex sodium versus placebo in the treatment of acute bipolar depression: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Bipolar disorders (BDs) are defined by mania and hypomania, but
      depressions occur more frequently, last longer, and lead to significant
      disability. Divalproex is the most frequently prescribed anticonvulsant
      medication for BD. While some evidence suggests that divalproex prevents
      depressive episodes during maintenance treatment, it is not commonly used in the
      treatment of acute depression, and there is a perception that there is little
      evidence to support its efficacy. METHODS: We conducted a meta-analysis of
      randomized placebo-controlled trials assessing the efficacy of divalproex in
      acute BD depression. We searched MEDLINE and the Cochrane Database of Systematic
      Reviews using the search terms "divalproex AND bipolar depression", "valproate
      AND bipolar depression", and "valproic acid AND bipolar depression". We also
      accessed the databases of clinical trial registries, including
      www.ClinicalTrials.gov, www.who.int/ictrp, http://isrctn.org,
      http://www.mrw.interscience.wiley.com/cochrane/cochrane_clcentral_articles_fs.htm
      , and www.ClinicalStudyResults.org. All English-language, randomized, double
      blind, placebo-controlled trials assessing the efficacy of divalproex monotherapy
      in the treatment of BD depression were included in the analysis. Data were
      subjected to meta-analysis to determine the relative risks of response and
      remission, and combined to estimate average response and remission rates.
      RESULTS: We identified four trials, with a total sample size of 142 patients. The
      relative risks of response (RR=2.10, p=0.02) and remission (RR=1.61, p=0.04) were
      significantly greater for divalproex than placebo. Mean response rates were 39.3%
      for divalproex and 17.5% for placebo, and mean remission rates were 40.6% and
      24.3%, respectively. LIMITATIONS: The total sample size in the four trials was
      small. CONCLUSIONS: These results provide preliminary evidence that divalproex is
      efficacious in the treatment of BD depression.

PMID- 20044143
TI  - Relationship between whole blood serotonin and repetitive behaviors in autism.
AB  - This study was conducted to examine the relationship between whole blood
      serotonin level and behavioral symptoms in 78 subjects with autism. No
      significant associations were found between serotonin level and the primary
      behavioral outcome measures. However, a significant inverse relationship between
      serotonin level and self-injury was demonstrated.

PMID- 20044144
TI  - A prospective study of predictors of depression symptoms in police.
AB  - Police work is one of the most stressful occupations. Previous research has
      indicated that work stress and trauma exposure may place individuals at
      heightened risk for the development of depression symptomatology. This
      prospective longitudinal study was designed to examine predictors of depression
      symptoms in police service. Participants comprised 119 healthy police recruits
      from an ongoing prospective study. They completed baseline measures of depression
      symptoms, childhood trauma exposure, neuroticism, and self-worth during academy
      training. Follow-up measures of depression symptoms, PTSD symptoms, critical
      incident exposure, negative life events, and routine work environment stress were
      assessed after 12 months of police service. Hierarchical linear regression
      analysis was conducted to examine predictors of current levels of depression
      symptoms, controlling for baseline depression symptoms and current PTSD symptoms.
      Greater childhood trauma exposure, lower self-worth during training, and greater
      perceived work stress in the first year of police service predicted greater
      depression symptoms at 12 months. Depression symptoms at 1 year of police service
      were partly independent from PTSD symptoms at 12 months. Greater childhood trauma
      exposure and lower self-worth during training may be important variables to
      screen as risk factors for duty-related depression. Strategies to reduce routine
      work environment stress have the potential to decrease duty-related depression in
      law enforcement.

PMID- 20044145
TI  - A case report of frontonasal dysplasia.
AB  - The following report describes a case of mild frontonasal dysplasia, a rare
      congenital anomaly affecting the nose and frontal bone. Our patient was referred
      at 2 months of age with a complex nasal skin and tip deformity. This report
      outlines management of this patient and reviews the literature with regard to
      presentation and classification of this condition.

PMID- 20044146
TI  - Respiratory tract involvement in a child with epidermolysis bullosa simplex with
      plectin deficiency: a case report.
AB  - We report a rare case of a child with epidermolysis bullosa simplex (EBS) with
      plectin deficiency but without muscular dystrophy, with severe lesions of the
      oral cavity, oropharyngeal, hypopharyngeal, laryngeal, tracheal and bronchial
      mucosa. Case report and a review of the world literature are used. The literature
      review revealed only five similar patients with EBS without muscular dystrophy
      complicated by respiratory involvement. This paper highlights the potentially
      serious complications of the EB in the form of breathing, swallowing and speech
      difficulties and describes the specific problems encountered in the treatment of
      this patient. Epidermolysis bullosa (EB) is a group of severe hereditary
      diseases, primarily of the skin, but which can also involve the respiratory and
      gastrointestinal tract mucosa. Respiratory tract involvement is usually only
      found in certain types of EB. The oral cavity and oropharynx are involved more
      frequently than the hypopharynx, larynx and trachea. Involvement of laryngeal and
      tracheal mucosa is generally associated with an increased morbidity and
      mortality, numerous complications and therapeutic difficulties, and is more
      common in junctional EB and dystrophic EB than in EBS. We present a rare case of
      a child with EBS and plectin deficiency with pronounced lesions of respiratory
      tract mucosa from the oral cavity to the bronchi and even extending into the
      trachea. Deciding on tracheotomy requires thorough consideration and should not
      be taken lightly.

PMID- 20044147
TI  - Otitis media with effusion: recurrence after tympanostomy tube extrusion.
AB  - OBJECTIVE: The incidence rate of recurrence of otitis media with effusion (OME)
      in children after tympanostomy tube extrusion and the relationship between
      recurrence and tube retention time was investigated. Also relationship between
      recurrence rate and initial age of tube insertion was analysed. STUDY DESIGN: A
      retrospective case series of patients who had tympanostomy tube insertion.
      METHODS: A total of 91 children (169 ears) were reviewed. Ears of children
      divided into three groups according to retention time of tympanostomy tubes.
      Group I: tympanostomy tube retention time less than 6 months. Group II:
      tympanostomy tube retention time 6 months to 12 months. Group III: tympanostomy
      tube retention time 12 months or more. RESULTS: OME recurrence rate after tube
      extrusion was 20.7% in the study. The longer the tympanostomy tube retention time
      was the lower was the recurrence rate of OME. The comparison of the three groups
      indicated that recurrence rates were higher in group I (36.54%), than in group II
      (17.74%) and in group III (9.1%). There were statistically significant
      differences in recurrence rates between group I and group III, and between group
      I and II (p<0.05, p<0.05). However, the difference in recurrence rates between
      group II and group III was statistically not significant (p>0.05). In the
      preschool age group and school age group, the recurrence rates were 5.5% and
      15.4%, respectively. There was no significant difference between these two groups
      (p>0.05). OME recurrence was observed in 9.9% of males and in 11% of females.
      There was no significant difference in recurrence rates between males and females
      (p>0.05). CONCLUSION: After extrusion of tympanostomy tube, children should be
      followed-up regularly for recurrence of OME. The shorter the retention time of
      tympanostomy tubes was the higher was the recurrence rate. For the treatment of
      OME the ideal type of tubes should have the lowest complication and recurrence
      rates. Further studies are needed to ascertain the relationship between the
      incidence of OME and optimal tympanostomy tubes duration of tube stay in tympanic
      membrane. Therefore, new studies with larger series are necessary to investigate
      the correlation between the recurrence rates and different tympanostomy tubes
      after extrusion of tubes.

PMID- 20044148
TI  - Multiple Cu-ATPase genes are differentially expressed and transcriptionally
      regulated by Cu exposure in sea bream, Sparus aurata.
AB  - Copper (Cu) is an essential metal, although in excess is highly toxic due to its
      redox properties and, therefore intracellular Cu homeostasis is a highly
      regulated process. Cu-ATPases are pivotal regulatory, proteins of intracellular
      and bodily Cu homeostasis. Two Cu-ATPases, ATP7A and ATP7B with distinct,
      functions are found in mammals and herein we report the structure and expression
      under Cu stress of, homologues of ATP7A and ATP7B in gilthead sea bream (Sparus
      aurata), the first such report for any, fish. The deduced protein sequences of S.
      aurata ATP7A (saATP7A) and ATP7B (saATP7B), displayed 63% and 75% identity
      respectively to their human homologues. All characteristic structural, features
      of Cu-ATPases were conserved between fish and mammals, although the number of Cu
      binding, domains was less in fish ATP7B than in mammalian ATP7B. The tissue
      expression of sea bream, Cu-ATPases was similar to that observed in mammals,
      saATP7A being ubiquitously expressed, although low in liver, whilst saATP7B was
      mainly expressed in the intestine and liver. By analysis of the sequenced genomes
      of other species we have confirmed the presence of ATP7A and ATP7B genes in fish
      and propose that the presence of two Cu-ATPase genes in vertebrates represents a
      retention and neo-functionalization of a duplicated ancestral gene coincident
      with the development of a closed circulatory system and discrete hepato-biliary
      system. Expression of Cu-ATPase mRNA was changed after exposure to excess Cu in a
      manner dependent on exposure route and tissue type. Excess dietary Cu (130mgkg(
      1) Cu dry diet) reduced saATP7A mRNA levels in intestine, gill, kidney and liver,
      and increased hepatic saATP7B mRNA consistent with increased biliary excretion.
      Whilst after waterborne Cu exposure (0.3mgL(-1) Cu), expression of ATP7A mRNA was
      increased in intestine and liver and toxic responses were observed in gill and
      liver. Our results indicate that Cu-ATPases in both fish and mammals have similar
      functions in maintenance of Cu homeostasis and are consistent with previous
      physiological evidence from various fish species for the involvement of multiple
      Cu-ATPases in Cu transport. Furthermore, our evidence suggests that fish can
      detoxify excess dietary Cu relatively efficiently but are unable to cope with
      excess dissolved Cu in the water, demonstrating that the exposure route is
      critical to toxicity.

PMID- 20044149
TI  - QSAR-analysis and mixture toxicity as diagnostic tools: Influence of degradation
      on the toxicity and mode of action of diuron in algae and daphnids.
AB  - Even though the environmental occurrence of pesticide transformation products is
      well established, ecotoxicological data for transformation products are often
      lacking. Therefore, it remains an open question for regulators how to handle
      transformation products in the process of authorization and risk assessment.
      Transformation products may (1) possess a similar mode of toxic action as the
      parent compound, (2) exhibit unexpected effects towards non-target organisms or
      (3) contribute to overall mixture toxicity through baseline toxicity even if the
      specific activity of the parent compound is lost. In the present study, a
      systematic and integrated approach is presented to differentiate between these
      three options with the goal of identifying transformation products that
      significantly add to the risk posed by the parent compound. Quantitative
      structure-activity relationships (QSAR) and a toxic ratio (TR) analysis were used
      to evaluate the toxicity and mode of toxic action of the transformation products
      relative to the parent compound. In addition, mixture toxicity experiments were
      used as diagnostic tools to underpin the mode of action analysis and to elucidate
      whether the transformation products possess a similar risk potential as the
      parent compound. As an illustrative example, the phenylurea herbicide diuron was
      chosen since a sound basis of ecotoxicological data was available not only for
      diuron itself but also for most of its transformation products. Effects were
      investigated using the most sensitive species, algae, and the non-target organism
      Daphnia magna, for which a previous QSAR-analysis of literature data suggested a
      specific hazard. In the present study the primary transformation products 1-(3,4
      dichlorophenyl)-3-methlyurea (DCPMU), 3-(3-chlorophenyl)-1,1-dimethylurea
      (MCPDMU), and 1-(3,4-dichlorophenyl)urea (DCPU) were identified as specific
      toxicants in algae, but as baseline toxicants in daphnids. The subsequent loss of
      the methylurea group during degradation, which formed 3,4-dichloroaniline, led to
      a clear detoxification in algae but to an increase in toxicity in daphnids. It
      could be shown that 3,4-dichloroaniline acted as baseline toxicant in algae, but
      showed a specific mode of toxic action in daphnids. Mixture toxicity experiments
      confirmed this mode of action analysis.

PMID- 20044150
TI  - Exposure of rainbow trout milt to mercury and cadmium alters sperm motility
      parameters and reproductive success.
AB  - In the current work, seminal plasma was used for the first time as an incubation
      medium for monitoring short-time exposure effects of sublethal concentrations of
      mercury and cadmium ions on rainbow trout sperm. Sperm motility parameters (CASA)
      and hatching rates were used as gamete quality markers. Additionally live/dead
      sperm viability test and comet assay of DNA fragmentation were performed. We
      demonstrated that computer-assisted sperm motility analysis (CASA) may serve as a
      predictor of reproductive success, when milt contaminated with heavy metals is
      used. Results presented in this study demonstrate that mercury ions altered sperm
      motility characteristics at 1-10 mg Hg2+/l and 10 mg Cd2+/l and hatching rates at
      10 mg Hg2+/l and 10 mg Cd2+/l after 4h of exposure. Although mercury ions
      affected sperm motility parameters immediately after dilution with milt as well
      as at 4h of exposure, no differences in sperm motility parameters were found
      between intact and mercury-treated milt after 24h of exposure. Our results
      suggest that rainbow trout seminal plasma has a protective role against the toxic
      effects of mercury ions of rainbow trout sperm motility.

PMID- 20044151
TI  - Rhesus glycoprotein and urea transporter genes in rainbow trout embryos are
      upregulated in response to alkaline water (pH 9.7) but not elevated water
      ammonia.
AB  - Recent studies have shown that genes for the putative ammonia transporter, Rhesus
      glycoproteins (Rh) and the facilitated urea transporter (UT) are expressed before
      hatching in rainbow trout (Oncorhychus mykiss Walbaum) embryos. We tested the
      hypothesis that Rh and UT gene expressions are regulated in response to
      environmental conditions that inhibit ammonia excretion during early life stages.
      Eyed-up embryos (22 days post-fertilization (dpf)) were exposed to control (pH
      8.3), high ammonia (1.70 mmol l(-1) NH4HCO3) and high pH (pH 9.7) conditions for
      48h. With exposure to high water ammonia, ammonia excretion rates were reversed,
      tissue ammonia concentration was elevated by 9-fold, but there were no
      significant changes in mRNA expression relative to control embryos. In contrast,
      exposure to high water pH had a smaller impact on ammonia excretion rates and
      tissue ammonia concentrations, whereas mRNA levels for the Rhesus glycoprotein
      Rhcg2 and urea transporter (UT) were elevated by 3.5- and 5.6-fold, respectively.
      As well, mRNAs of the genes for H+ATPase and Na+/H+ exchanger (NHE2), associated
      with NH3 excretion, were also upregulated by 7.2- and 13-fold, respectively, in
      embryos exposed to alkaline water relative to controls. These results indicate
      that the Rhcg2, UT and associated transport genes are regulated in rainbow trout
      embryos, but in contrast to adults, there is no effect of high external ammonia
      at this stage of development.

PMID- 20044152
TI  - Factors influencing oral health-related quality of life (OHRQoL) among the frail
      elderly residing in the community with their family.
AB  - The purpose of the present study was to identify factors that influence quality
      of life (QoL) among frail elderly individuals residing in the community, in order
      to improve the level of home care related to oral health. Participants were 100
      pairs comprising elderly individuals requiring care and their family caregivers.
      Questionnaire items for the family caregivers related to demographic variables,
      hours spent caregiving per day, and duration of caregiving. Questionnaire items
      for the elderly recipients of care concerned demographic variables, activities of
      daily living (ADL), and cognitive status. According to bivariate analysis, oral
      health-related quality of life (OHRQoL) was significantly related to basic ADL,
      communication ADL (CADL), dysphagia risk, and duration of caregiving. From
      multiple regression analysis, dysphagia risk and CADL were extracted as factors
      influencing OHRQoL. Assessment of OHRQoL will be useful not only to detect oral
      health needs but also to evaluate the effect of oral health care in the elderly.

PMID- 20044153
TI  - Safety and efficacy of radiotherapy treatment in elderly patients with localized
      prostate cancer: a retrospective analysis.
AB  - The purpose of this study was to evaluate the feasibility and the activity of
      radiotherapy treatment in patients aged >=75 with prostate cancer (PC). From
      January 2000 to December 2007, 107 consecutive patients aged >=75 years received
      radiotherapy with radical intent for PC. Eighty-one patients received
      radiotherapy in combination with a 6 months androgen suppression therapy.
      Variables considered were age, stage, co-morbidities according to the adult co
      morbidity evaluation index (ACE-27) and performance status (PS). The median age
      was 79.1 years (range 76-87). The 23.4% of patients showed no co-morbidities,
      while the 46.7% had mild, 23.4% moderate, and 6.5% severe co-morbidities,
      respectively. All patients completed the planned radiation treatment. At a median
      follow-up of 37.8 months, the 5-year overall survival rate was 78%. There was a
      better survival for patients with no or mild co-morbidities (p<0.0001) and a good
      PS (p=0.009). The actuarial disease-free survival at 60 months was 75.8%.
      Difference in acute and late toxicity rate was detected between ACE-27 classes
      for diarrhea and marginally for urinary toxicity, but no difference was detected
      for different age. We conclude that compliance with radiotherapy is good and rate
      of toxicity is acceptable in elderly patients. Increasing severity of co
      morbidity may sufficiently shorten remaining life expectancy to cancel gains with
      radical radiotherapy. Further prospective trials are needed to confirm these
      results.

PMID- 20044154
TI  - Assessment of pain, fatigue, sleep and quality of life (QoL) in elderly
      hospitalized cancer patients.
AB  - As the proportion of older adults in the population continues to grow, the number
      of patients with cancer is expected to increase proportionally. In the previously
      conducted studies, data on elderly cancer patients were generally compared with
      the QoL scores of elderly patient group and with the data of non-cancer
      individuals. The purpose of this study was to examine differences in reported
      pain, fatigue, sleep problems and QoL between middle-aged and elderly
      hospitalized patients with cancer. We included 53 middle-aged (between 18 and 50
      years) hospitalized cancer patients and 47 elderly (>60 years) hospitalized
      cancer patients in this study. Pain (visual analog scale=VAS, verbal pain
      rating), fatigue (brief fatigue inventory=BFI), sleep problems, QoL (Short Form
      36=SF36), and European Organization for Research and Treatment of Cancer (EORTC)
      QoL-C30 data were gathered using standardized measures. In the elderly group, no
      significant difference was detected in terms of VAS, verbal pain rating, fatigue,
      fatigue type, sleep problems and QoL scores (p>0.05). When the two age groups
      were compared, BFI scores were found to be significantly high among the elderly
      patients (p<0.05). A significant relationship was observed in both age groups
      between the scores of pain, fatigue and sleep problems, and QoL (p<0.05). Elderly
      hospitalized cancer patients did not demonstrate a distinctive difference in
      terms of pain, sleep and QoL compared to the younger group. The relationship
      between pain, fatigue, sleep and QoL should be definitely kept in mind in
      clinical practice.

PMID- 20044155
TI  - Effects of a physical training and nutritional intervention program in frail
      elderly people regarding habitual physical activity level and activities of daily
      living--a randomized controlled pilot study.
AB  - The aim of this randomized controlled pilot study is to describe the effects of a
      physical training and nutritional intervention program on the physical activity
      level and activities of daily living (ADL) in frail elderly people. Ninety-six
      community-dwelling frail elderly people (58 women) above the age of 75 were
      included in the study. The 12-week physical and/or nutritional intervention
      program was followed by six months of home-based exercises for the training
      groups, followed up with training diaries. At baseline the subjects were screened
      for physical activity level, walking habits, and ADL. These measurements were
      repeated immediately after the intervention at 3 months, and at 2nd follow-up at
      9 months. ADL data were also collected 24 months after baseline at 3rd follow-up.
      The intention-to-treat analyses showed an increase of the habitual physical
      activity level and walking duration at 1st follow-up for the two training groups
      compared to the other groups. These increases remained at 2nd follow-up. The
      nutrition intervention did not show any significant results. No significant
      effects on ADL were shown however, there were moderate correlations between
      increases in physical activity level and ADL as well as between the amounts of
      home-based exercises and ADL for the two training groups.

PMID- 20044156
TI  - Bioelectric impedance phase angle is associated with hospital mortality of
      geriatric patients.
AB  - Malnutrition is regularly associated with weight loss and changes in body
      composition, which lead to an increase in disability, complications and
      mortality. Bioelectric impedance analysis (BIA) is a simple and non-invasive
      bedside body composition analysis technique. In particular, bioelectric impedance
      phase angle (PA) has been shown to predict prognosis and mortality in several
      clinical conditions. The purpose of this study was to determine the relationship
      of BIA measurements and hospital mortality in multimorbid geriatric patients. The
      data obtained from the routine clinical admissions of 1071 consecutive patients
      (783 women and 288 men, age 81.4+/-8.5 years) to a geriatric hospital unit was
      analyzed retrospectively. A significant difference of PA (50 kHz) between
      survivors (4.2+/-1.1 degrees ) and non-survivors (3.6+/-1.2 degrees ; p<0.001) of
      the hospital stay could be detected. Subjects with a PA below 3.5 degrees  showed
      a significant fourfold increased hospital mortality of 20% (95% CI=15-24%)
      compared to all other subjects (5%; 95% CI=4-7%). No calculated parameters of BIA
      reflecting body composition were associated with hospital mortality. Although the
      extent to which the PA may be regarded as a marker of nutritional state is still
      controversial, it was associated with hospital mortality in geriatric patients.

PMID- 20044158
TI  - Combining surveillance and expert evidence of viral hemorrhagic septicemia
      freedom: a decision science approach.
AB  - The ability to combine evidence streams to establish disease freedom or
      prioritize surveillance is important for the evaluation of emerging diseases,
      such as viral hemorrhagic septicemia virus (VHSV) IVb in freshwater systems of
      the United States and Canada. Waterways provide a relatively unconstrained
      pathway for the spread of VHSV; and structured surveillance for emerging disease
      in open systems has many challenges. We introduce a decision framework for
      estimating VHSV infection probability that draws from multiple evidence streams
      and addresses challenges associated with the assessment of emerging disease.
      Using this approach, historical and risk-based evidence, whether empirical or
      expert-derived, supplement surveillance data to estimate disease probability.
      Surveillance-based estimates of VHSV prevalence were described using beta
      distributions. Subjective likelihood ratios (LRs), representing contextual risk,
      were elicited by asking experts to estimate the predicted occurrence of risk
      factors among VHSV-affected vs. VHSV-unaffected watersheds. We used the odds form
      of Bayes' theorem to aggregate expert and surveillance evidence to predict the
      risk-adjusted posterior probability of VHSV-infection for given watersheds. We
      also used LRs representing contextual risk to quantify the time value of past
      surveillance data. This evidence aggregation model predicts disease probability
      from the combined assessment of multiple sources of information. The method also
      provides a flexible framework for iterative revision of disease freedom status as
      knowledge and data evolve.

PMID- 20044159
TI  - Prevalence and risk factors for Salmonella enterica subsp. enterica contamination
      in French breeding and fattening turkey flocks at the end of the rearing period.
AB  - An epidemiological study was conducted to estimate the prevalence of Salmonella
      spp. contamination in French commercial breeding and fattening turkey flocks at
      the end of the rearing period, as part of a European Union-wide baseline study.
      Two hundred and five breeding turkey flocks and three hundred and two fattening
      turkey flocks were included in the study, between October 2006 and September
      2007. The Salmonella status of flocks was assessed by collecting five
      environmental faeces samples, analysed by classical bacteriological method. The
      prevalence of Salmonella positive flocks was 1.5% for breeding turkeys and 15.6%
      (95% CI: 11.5; 19.7) for fattening turkeys. Information on potential risk factors
      of the turkey flock being Salmonella positive was collected by questionnaire at
      the same time as sample collection. The association between management practices,
      general hygiene and Salmonella status in French turkey flocks was assessed by
      logistic regression. The risk of Salmonella contamination in fattening turkey
      flocks was decreased when floors were disinfected during decontamination
      procedures, when Salmonella detection was carried out during rearing and when
      there was a metering pump in the house. However in this study, the risk was
      increased when the farmer used a footbath at the turkey house entrance. Risk
      factors for Salmonella in breeding turkey flocks could not be subjected to formal
      statistical analysis since only three flocks were contaminated.

PMID- 20044161
TI  - Diabetic kidney disease: act now or pay later.

PMID- 20044160
TI  - Potential of siderophore-producing bacteria for improving heavy metal
      phytoextraction.
AB  - Phytoremediation holds promise for in situ treatment of heavy metal contaminated
      soils. Recently, the benefits of combining siderophore-producing bacteria (SPB)
      with plants for metal removal from contaminated soils have been demonstrated.
      Metal-resistant SPB play an important role in the successful survival and growth
      of plants in contaminated soils by alleviating the metal toxicity and supplying
      the plant with nutrients, particularly iron. Furthermore, bacterial siderophores
      are able to bind metals other than iron and thus enhance their bioavailability in
      the rhizosphere of plants. Overall, an increase in plant growth and metal uptake
      will further enhance the effectiveness of phytoremediation processes. Here, we
      highlight the diversity and ecology of metal resistant SPB and discuss their
      potential role in phytoremediation of heavy metals.

PMID- 20044162
TI  - A Telemedicine system based on Internet and short message service as a new
      approach in the follow-up of patients with gestational diabetes.
AB  - To evaluate the feasibility of a Telemedicine system based on Internet and short
      message service in the follow-up of patients with gestational diabetes. Compared
      to control group, Telemedicine group reduced 62% the number of unscheduled face
      to-face visits, and 82.7% in the subgroup of insulin-treated patients, improving
      patient satisfaction, and achieving similar pregnancy and new born outcomes.

PMID- 20044163
TI  - Overcoming barriers to diabetes care: Perceived communication issues of
      healthcare professionals attending a pilot Diabetes UK training programme.
AB  - As part of our evaluation of the Diabetes UK Careline workshop "Overcoming
      barriers to diabetes care", we received feedback from 18 healthcare
      professionals. Generally, they felt competent in identifying patients'
      psychosocial issues but less knowledgeable/skilled in handling them. Lack of
      time, privacy and support were barriers to addressing patients' psychosocial
      concerns.

PMID- 20044164
TI  - Lower copy numbers of the chemokine CCL3L1 gene in patients with chronic
      hepatitis C.
AB  - BACKGROUND & AIMS: Recently, variation of gene copy numbers was recognized as a
      novel type of common genetic diversity, but its impact on viral hepatitis is
      unknown. Here, we determine the influence of copy number variation on the
      susceptibility and disease severity in hepatitis C virus (HCV) infection,
      investigating copy number variants (CNVs) of the chemokine CCL3L1 gene, which
      encodes a potent CCR5 ligand. METHODS: CNVs were determined in 254 patients with
      chronic hepatitis C, 144 HCV/HIV co-infected patients, and 210 HCV negative
      controls, using quality-controlled real-time fluorescent dye-labeled quantitative
      PCR. Liver biopsies were obtained from HCV infected patients. RESULTS: Copy
      numbers of the CCL3L1 gene range from 0 to 12 (mean 2.7+/-1.4 copies). Patients
      with two or less copies are over-represented in the HCV infected cohort compared
      to HCV negative controls (odds ratio [OR] 1.54; p=0.02). CCL3L1 copies are
      shifted to lower numbers in HCV infected patients (means 2.6 vs. 2.9 in controls;
      p=0.011). HCV/HIV co-infected patients carry even lower CCL3L1 copy numbers
      compared to controls (means 2.2 vs. 2.9; p<0.001), with a higher proportion of
      patients possessing two or less copies (OR=3.42; p<0.001). No association was
      detected between CCL3L1 copy numbers and histological grades of inflammation or
      stages of fibrosis. CONCLUSIONS: Lower CCL3L1 gene copy number compared to the
      population median is associated with chronic hepatitis C. Copy number variation
      of host genes represents a novel class of genetic diversity associated with viral
      hepatitis.

PMID- 20044165
TI  - A survey exploring knowledge and perceptions of general practitioners towards the
      use of generic medicines in the northern state of Malaysia.
AB  - OBJECTIVES: The objective of this study was to evaluate the general
      practitioners' (GPs') knowledge and perceptions towards generic medicines in a
      northern state of Malaysia. METHOD: A postal cross-sectional survey involving
      registered GPs in Penang, Malaysia was undertaken. A 23-item questionnaire was
      developed, validated and administered on the GPs. Eighty-seven GPs responded to
      the survey (response rate 26.8%). RESULTS: The majority of the respondents
      (85.1%) claimed that they actively prescribed generic medicines in their
      practice. On the other hand, only 4.6% of the respondents correctly identified
      the Malaysia's National Pharmaceutical Control Bureau's bioequivalence standard
      for generic products. There were misconceptions among the respondents about the
      concepts of "bioequivalence", "efficacy", "safety", and "manufacturing standards"
      of generic medicines. GPs in this survey believed that a standard guideline on
      brand substitution process, collaboration with pharmacists, patient education and
      information on safety and efficacy of generic medicines were necessary to ensure
      quality use of generics. Furthermore, advertisements and product bonuses offered
      by pharmaceutical companies, patient's socio-economic factors as well as
      credibility of manufacturers were factors reported to influence their choice of
      medicine. CONCLUSION: Although it appeared that GPs have largely accepted the use
      of generic medicines, they still have concerns regarding the reliability and
      quality of such products. GPs need to be educated and reassured about generic
      products approval system in Malaysia concerning bioequivalence, quality, and
      safety. The current findings have important implications in establishing generic
      medicines policy in Malaysia.

PMID- 20044166
TI  - Understanding the onset of hybrid speciation.
AB  - Natural hybridization between closely related taxa is a common phenomenon in both
      plants and animals. Hybridization has often been viewed as a destructive force
      that could erode established gene pools, but it is increasingly being recognized
      as a potentially creative force in evolution because it can lead to a mixture of
      novel genotypes, some of which have the potential for rapid adaptation to new
      environmental conditions. However, the evolutionary dynamics leading to the
      emergence of newly adapted gene pools after hybridization are largely unexplored.
      Here, we argue that the identification and analysis of the dynamic processes that
      occur after the first contact deserve specific attention, because this is the
      phase where hybrid speciation is most different from other forms of speciation.

PMID- 20044167
TI  - Interactions between Glomus species and Rhizobium strains affect the nutritional
      physiology of drought-stressed legume hosts.
AB  - The growth of legume plants is usually enhanced by the dual symbiosis of
      arbuscular mycorrhizal (AM) fungi and Rhizobium bacteria. However, most reports
      on this topic have been carried out under optimal water regime conditions. Here,
      four Phaseolus vulgaris varieties were single or dual inoculated with two
      different AM fungus and/or two different Rhizobium strains. All plants were grown
      under moderate drought conditions. Surprisingly, most of the biological
      treatments involving one fungus and one Rhizobium together caused a deleterious
      effect on plant growth. However, these negative effects were dependent on the P.
      vulgaris variety used as well as on the symbionts implicated. The results showed
      that AM symbiosis inhibited nodule development and N(2) fixation, causing
      diminution of plant growth. Therefore, under moderate drought conditions, the
      dual symbiosis formed by AM fungi and Rhizobium can be deleterious to P. vulgaris
      growth depending on the plant variety and the symbionts involved. Thus, under
      these common stress conditions, selection for the appropriated symbionts to each
      P. vulgaris variety is needed.

PMID- 20044168
TI  - Short-term high temperature growth conditions during vegetative-to-reproductive
      phase transition irreversibly compromise cell wall invertase-mediated sucrose
      catalysis and microspore meiosis in grain sorghum (Sorghum bicolor).
AB  - Grain sorghum (Sorghum bicolor) crop yield is significantly compromised by high
      temperature stress-induced male sterility, and is attributed to reduced cell wall
      invertase (CWI)-mediated sucrose hydrolysis in microspores and anthers leading to
      altered carbohydrate metabolism and starch deficiency in pollen (Jain et al.,
      2007). Sorghum plants were grown under season-long ambient (30/20 degrees C day
      time maximum/night-time minimum) or high temperature stress (HS, 36/26 degrees C)
      environments, or reciprocally transferred for 5-10 days between either
      temperature regimens through panicle and microspore developmental stages.
      Quantitative RT-PCR analyses for CWI gene SbIncw1, plasma membrane H(+)-ATPase
      (Mha1) and sugar transporter proteins (OsSUT3 and OsMST7 homologs in sorghum),
      starch deficiency and pollen sterility data are presented to confirm HS
      sensitivity of pre- and post-meiotic stages of sorghum microsporogenesis. Heat
      stress-induced reduction in Incw transcriptional activity during microspore
      meiosis was irreversible despite return of optimal growth temperature conditions
      through further reproductive development.

PMID- 20044170
TI  - [Has vitamin D(3) dosage improved in Spain? Current levels in a population
      sample].
AB  - INTRODUCTION: According to current classifications, the metabolite of greatest
      clinical interest to evaluate vitamin D(3) dosage is 25-hydroxyvitamin D(3) with
      a reference interval of approximately 10-70ng/ml, although many authors consider
      values of approximately 40ng/ml or 100nmol/l to be desirable. According to these
      definitions, three out of four people in Spain would have vitamin D(3)
      deficiency. MATERIAL AND METHOD: The RIA-CT technique was used for diagnosis of
      25(OH)D(3) to determine the population status. Subsequently, a case-control study
      was performed to evaluate the relationship between distinct diseases and vitamin
      D(3) deficiency. RESULTS: A total of 73.2% of the cases were found to be within
      the range considered acceptable, according to the present classification. One
      hundred percent of the control group and healthy menopausal women who did not
      receive any kind of vitamin supplement had levels of 40 ng/ml or more. DISCUSSION
      AND CONCLUSIONS: Our results indicate that the prior situation of a high
      prevalence of vitamin D(3) deficiency has improved and that levels are now
      acceptable in 26.8% of the population, with a mean value of 46.2 ng/ml,
      considering 10-70 ng/ml as the reference range.

PMID- 20044172
TI  - [Fear of falling].
AB  - Fear of falling (FF) can be considered as a protective response to a real threat,
      preventing the elderly from performing activities with high risk of falling, but
      can also lead to a restriction of the activities that will result in a long-term
      adverse effect on social, physical or cognitive functions. There is a prevalence
      of FF in 30% in the elderly who have no history of falls, and double that in
      those with a history of falling. Its prevalence is increased in women and with
      advanced age. Several scales have been developed to measure the psychological
      effects of FF, among which are noted are, the Fall Efficacy Scale (FES), the
      Activities-specific Balance and Confidence Scale (ABC), and the survey of
      activities and fear of falling in the elderly (SAFE). It has negative
      consequences in the functionality, the subjective feeling of well-being, and in
      the consequent loss of independence. The functional and physical deterioration,
      or the quality of life is clearly related to the FF, although it has not been
      established if these factors are cause or effect. Multiple interventions have
      been recommended, bringing about changes that reinforce their confidence to carry
      out activities. Interventions and research should promote a realistic and
      appropriate approach to the risk of falls and teach the elderly to perform
      activities safely. The reduction in FF is an important goal in itself to improve
      the subjective feeling of well-being, and the benefits could be increased if this
      reduction was also accompanied by an increase in safe behaviour, social
      participation, and activities of the daily life.

PMID- 20044171
TI  - [Association between anxiolytic and antidepressant consumption and psychiatric
      symptoms in the elderly].
AB  - INTRODUCTION: Many studies have reported excessive consumption of psychotropic
      drugs in the elderly but none have related psychotropic drug use to psychiatric
      symptoms and sleep disorders in community-dwelling patients aged more than 65
      years old in Spain. MATERIAL AND METHODS: We performed a cross sectional study in
      a representative sample (9,739 persons) from the population aged more than 55
      years old in the city of Zaragoza in 2001. A total of 3,714 persons aged more
      than 65 years old were interviewed. The data belonged to the ZARADEMP project.
      RESULTS: The mean age of the sample was 76.9 years (59.2% women and 40.8% men).
      Anxiolytics or antidepressants were consumed by 22.6% of the sample. A diagnosis
      of depression was made in 12.9%, anxiety in 1.6% and insomnia in 36%. We found
      high consumption of anxiolytics, especially in persons with depression (42.2%)
      and low consumption of antidepressants, especially in persons with a diagnosis of
      depression (15.4%) and in those with depressive symptoms (8.2%). CONCLUSIONS: A
      correct psychiatric diagnosis is essential before psychotropic drugs are used to
      ensure appropriate treatment of the elderly with psychiatric symptoms.

PMID- 20044173
TI  - [Kaposi's sarcoma: an unusual cause of persistent edema in an elderly woman].

PMID- 20044174
TI  - [Staphylococcus aureus infection in an acute geriatric unit].
AB  - OBJECTIVE: The aim of this study was to determine the risk of mortality,
      functional decline and institutionalization, as well as the hospital cost
      associated with patients with methicillin-resistant Staphylococcus aureus (MRSA)
      infection in an Acute Geriatric Unit (AGU). MATERIAL AND METHODS: We
      retrospectively gathered data on patients admitted to the AGU over a 5-year
      period (from 1/1/2001 to 1/1/06). Mortality, institutionalization, functional
      impairment at discharge, length of hospital stay, and hospital costs were
      compared between patients with and without MRSA. MRSA infection was documented by
      the microbiology department using culture and antibiogram, as well as by clinical
      diagnosis of hospital infection registered in the medical record. RESULTS: Data
      were obtained from 47 patients with MRSA (mean age 86.15+/-5.5 years) and from
      4281 patients without MRSA (mean age 85.25+/-6 years). MRSA-infected patients had
      higher mortality (25.5% vs. 7.7%, p<0.001), worse functional status at discharge
      (Barthel index 39.43+/-33.05 vs. 55.24+/-34.99, p<0.01) and more frequent
      institutionalization (29% vs. 9%, p<0.001). Longer length of hospital stay
      (22.15+/-13.67 vs. 10.64+/-7.69 days, p<0.001) and higher hospital cost per
      patient (7517.71+/-4639.59 vs 3611.21+/-2609.98 euro, p<0.001) were also
      observed. In the multivariate analysis adjusted by age, sex, and baseline
      functional and cognitive status, MRSA infection was independently associated with
      higher mortality (OR=3.92; 95% CI=1.95-7.86), worse functional status at
      discharge (OR=2.48; 95% CI=1.22-5.01), institutionalization at discharge
      (OR=6.50; 95% CI=2.60-12.22), and substantial increase in length of hospital stay
      (Beta coefficient=11.55 days; 95% CI=9.32-13.75). CONCLUSION: MRSA infection in
      the AGU is associated with higher mortality, worse functional status at discharge
      and a higher incidence of institutionalization, as well as significantly longer
      length of stay and higher hospital costs.

PMID- 20044175
TI  - [Dyspnea and oppressive cervical pain in an 86-year-old woman].

PMID- 20044176
TI  - [Gait speed as an indicator of fragility in community-dwelling elders in Lima,
      Peru].
AB  - OBJECTIVE: To determine the gait speed cut-off point that indicates frailty in
      community-dwelling elderly people in Lima, Peru. MATERIAL AND METHODS: Gait speed
      was measured over a distance of 8m and frailty was determined by using Fried's
      criteria in a sample of 246 elderly adults. A cluster analysis was applied to
      establish the gait speed cut-off point determining the presence of frailty.
      RESULTS: The mean age was 69.9 years (SD: 7.6) and 59.8% were women. The
      frequency of frailty was 7.7% and the frequencies of comorbidity and dependency
      were 12.6% and 6.5%, respectively. The mean gait speed was 0.9 m/s (SD: 0.2) and
      the gait speed cut-off point indicating frailty was 0.7 m/s. CONCLUSION: Gait
      speed less than 0.7 m/s is an indicator of frailty in community-dwelling elderly
      people in Lima, Peru.

PMID- 20044177
TI  - [Ataxia secondary to valproate. The importance of the choice of anti-epileptic
      treatment in the elderly].

PMID- 20044179
TI  - [Validity of quality indicators of the prescription of antiasthmatic agents
      calculated in defined daily doses].

PMID- 20044178
TI  - [Effectiveness of reevaluation of admission of patients with poor functional
      status].
AB  - INTRODUCTION: Acute care hospitals are one of the healthcare settings that pose
      the greatest risk of inefficiency and iatrogeny in the elderly. The term
      "inappropriate admission" refers to those admissions that could have been dealt
      with in an outpatient clinic or in a hospital with a lower level of care. We
      designed an intervention in the Emergency Department of our hospital (Hospital
      Universitario de Getafe, Madrid) with the aim of reducing the percentage of
      inappropriate admissions in the elderly. MATERIAL AND METHOD: A geriatrician
      reevaluated admissions of patients aged 75 years old and above, with established
      severe dependence in either of the two areas evaluated (physical and cognitive)
      and who were candidates for admission to the Acute Unit. RESULTS: Of 380 patients
      who were reevaluated, 240 were discharged instead of being admitted. These
      patients were referred to different levels of care: 123 patients (51.25%) were
      monitored in the Community Care Unit, 12 (5%) were referred to other hospitals
      with a lower level of care (Palliative Unit and/or Long Term care Unit) and 8
      patients (3.34%) were sent to the outpatient clinic. By avoiding 240 admissions,
      an estimated 1992 stays were prevented, representing a saving of 619, 512 euros.
      CONCLUSION: Assessment of elderly patients by geriatricians in the Emergency
      Department and the availability of distinct levels of care are effective
      resources to avoid inappropriate admissions.

PMID- 20044181
TI  - Enjoyable learning: the role of humour, games, and fun activities in nursing and
      midwifery education.
AB  - Education that captures the attention of students is an essential aspect of
      promoting meaningful, active learning. Rather than standing at the front of a
      group of learners simply speaking about a topic, teachers have the opportunity of
      livening up their teaching with humour, games, and other fun activities. This
      article critically evaluates the benefits and limitations of humour within
      nursing education as well as the use of games and fun activities as teaching
      strategies. Examples of various games and interactive activities are also
      provided.

PMID- 20044180
TI  - Evidence for teaching practice: the impact of clickers in a large classroom
      environment.
AB  - As the number of nursing students increases, the ability to actively engage all
      students in a large classroom is challenging and increasingly difficult.
      Clickers, or student response systems (SRS), are a relatively new technology in
      nursing education that use wireless technology and enable students to select
      individual responses to questions posed to them during class. The study design
      was a quasi-experimental comparison with one section of an adult medical-surgical
      course using the SRS and one receiving standard teaching. No significant
      differences between groups on any measure of performance were found. Focus groups
      were conducted to describe student perceptions of SRS. Three themes emerged:
      Being able to respond anonymously, validating an answer while providing immediate
      feedback, and providing an interactive and engaging environment. Although the
      clickers did not improve learning outcomes as measured by objective testing,
      perceptions shared by students indicated an increased degree of classroom
      engagement. Future research needs to examine other potential outcome variables.

PMID- 20044182
TI  - Therapeutic potential of Ganoderma lucidum (Fr.) P. Karst. against the declined
      antioxidant status in the mitochondria of post-mitotic tissues of aged mice.
AB  - BACKGROUND & AIMS: Post-mitotic cells such as brain and heart cells are
      particularly vulnerable to oxidative damages during ageing. In this study, we
      evaluated the effect of Ganoderma lucidum on the antioxidant status in the
      mitochondria of heart and brain of aged mice. METHODS: The effect was evaluated
      by estimating the activities of manganese-superoxide dismutase (Mn SOD),
      glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT)
      as well as levels of reduced glutathione (GSH), lipid peroxidation, advanced
      oxidation protein products (AOPP) and reactive oxygen species (ROS) in the heart
      and brain mitochondria of aged mice after oral administration of ethanolic
      extract of G. lucidum (50 and 250mg/kg), once daily for 15 days. The effect was
      compared with that of aged and young control animals. dl-alpha-lipoic acid
      (100mg/kg) was taken as the positive control. RESULTS: Administration of G.
      lucidum extract significantly (p<0.05) elevated the levels of GSH as well as
      activities of Mn SOD, GPx, and GST and decreased significantly (p<0.05) the
      levels of lipid peroxidation, AOPP and ROS. CONCLUSION: G. lucidum administration
      could improve the age-related decline of antioxidant status which was partly
      ascribed to free radical scavenging activity.

PMID- 20044183
TI  - Reduced nutritional status among multiple myeloma patients during treatment with
      high-dose chemotherapy and autologous stem cell support.
AB  - BACKGROUND & AIMS: Multiple myeloma (MM) ranks among the most frequent blood
      cancers in adults. Optimal treatment consists of high-dose chemotherapy and
      autologous stem cell transplantation. Health-related quality of life (HRQoL) is
      reduced before, during, and after therapy. Several HRQoL items are associated
      with nutritional health, e.g., nausea/vomiting, appetite loss and fatigue. It is
      unknown whether nutritional status in MM is affected by treatment. Hence we
      assessed nutritional status before, during and (1/2) year after treatment-start.
      METHODS: We applied anthropometry (height, weight, hand-grip strength, triceps
      skinfold) and plasma concentrations of biomarkers to assess nutritional status.
      HRQoL was determined with the EORTC QLQ-C30 questionnaire. RESULTS: The
      anthropometrical parameters all decreased (p<0.05) during treatment, but were
      restored at the end of the observation period. Albumin and the fat-soluble
      vitamins D and E followed a similar pattern, whereas transferrin and vitamin A
      were unchanged (p>0.05). Interestingly, markers of thyroid function declined and
      remained low (p<0.05) even 6 months after start of therapy. Nutrition-associated
      symptoms used as markers of HRQoL worsened during therapy, but returned to pre
      therapy levels. CONCLUSION: Intensive therapy in MM is associated with a decline
      in both nutritional status and health-related quality of life.

PMID- 20044184
TI  - 134Cs uptake by four plant species and Cs-K relations in the soil-plant system as
      affected by Ca(OH)2 application to an acid soil.
AB  - Three rates of Ca(OH)(2) were applied to an acid soil and the (134)Cs uptake by
      radish, cucumber, soybean and sunflower plants was studied. The (134)Cs
      concentration in all plant species was reduced from 1.6-fold in the sunflower
      seeds to 6-fold in the soybean vegetative parts at the higher Ca(OH)(2) rate.
      Potassium (K) concentration in plants was also reduced, but less effectively. The
      significantly decreased (134)Cs-K soil to plant distribution factors (D.F.)
      clearly suggest a stronger effect of soil liming on (134)Cs than on K plant
      uptake. This observation was discussed in terms of ionic interactions in the soil
      matrix and within the plants. The results also indicated that the increased
      Ca(2+) concentration in the exchange phase and in the soil solution along with
      the improved root activity, due to the soil liming, enhanced the immobilization
      of (134)Cs in the soil matrix and consequently lowered the (134)Cs availability
      for plant uptake.

PMID- 20044185
TI  - Pandemic A (H1N1) 2009 influenza-an enhanced hazard during pregnancy.

PMID- 20044186
TI  - Acculturative and neighborhood influences on subjective social status among
      Spanish-speaking Latino immigrant smokers.
AB  - Subjective social status (SSS) reflects an individual's perception of her/his
      relative position in the social hierarchy. However, little is known about
      culturally-relevant, multilevel predictors of low SSS among low socioeconomic
      status (SES), minority populations. The goal of this study was to identify
      individual- and neighborhood-level variables predicting SSS among 297 Spanish
      speaking Latino immigrant smokers living in several locations in Texas, with an
      emphasis on the association of SSS with acculturative and socioeconomic
      variables. Participants were recruited and enrolled through the National Cancer
      Institute's Cancer Information Service from August 2002 to March 2004.
      Determinants of SSS were explored using a series of linear regressions. In
      analyses adjusting for demographics (including objective indicators of SES),
      speaking Spanish at home and work and living in economically disadvantaged
      neighborhoods, respectively, were associated with low SSS. However, in analyses
      including demographics, acculturation, and neighborhood characteristics, only
      income, education, and acculturation remained associated with SSS. Consistent
      with results from a previous study in the area (Franzini & Fernandez-Esquer,
      2006), less acculturation predicted low SSS among immigrant Latino smokers.
      However, unlike previous research, these associations were maintained after
      controlling for SES. Results suggest that the density of less acculturated
      Latinos within economically deprived neighborhoods might account for the
      disappearance of neighborhood effects in the final model.

PMID- 20044187
TI  - Smoking, stigma and tobacco 'denormalization': Further reflections on the use of
      stigma as a public health tool. A commentary on Social Science & Medicine's
      Stigma, Prejudice, Discrimination and Health Special Issue (67: 3).
AB  - In recent years, addictions policy has stressed the need to counteract
      stigmatization in order to promote public health. However, as recent observers
      have noted, through the widespread implementation of tobacco 'denormalization'
      strategies, tobacco control advocates appear to have embraced the use of stigma
      as an explicit policy tool. In a recent article, Ronald Bayer (2008) argues that
      the mobilization of stigma may effectively reduce the prevalence of smoking
      behaviors linked to tobacco-related morbidity and mortality and is therefore not
      necessarily antithetical to public health goals. This commentary takes up this
      question of whether stigmatizing smoking may ultimately serve the interests of
      public health. Through an examination of the unique contours of tobacco control
      policy, we suggest that stigmatizing smoking will not ultimately help to reduce
      smoking prevalence amongst disadvantaged smokers - who now represent the majority
      of tobacco users. Rather, it is likely to exacerbate health-related inequalities
      by limiting smokers' access to healthcare and inhibiting smoking cessation
      efforts in primary care settings.

PMID- 20044189
TI  - Secondary surgery for cicatricial complications of facial injury.
AB  - PURPOSE: To investigate the nature of surgical revision procedures necessitated
      by cicatricial complications of facial injury. PATIENTS AND METHODS: All patients
      who had facial trauma in a period of approximately 5 years managed by a single
      surgeon were reviewed. Of these, 36 were found to have undergone secondary
      revision procedures arising specifically from scar-related complications.
      RESULTS: The average age of patients undergoing revision surgery was 34 years; 27
      of the 36 patients (75%) were men, and 9 of the 36 (25%) required multiple
      revision surgical visits. The most common cause of injury was motor vehicle
      collision; the interval between the initial trauma and the first revision surgery
      was most commonly 6 to 12 months. Scar-related complications were categorized on
      the face by anatomic subsite; they occurred most frequently on the
      forehead/cheeks/chin area, with the eyes/periorbital area the second most
      frequent location. One hundred twelve discrete surgical procedures (as per
      current procedural terminology) were performed on these 36 patients to address
      the cicatricial sequelae of their initial injuries. CONCLUSIONS: Facial trauma
      can frequently entail secondary morbidity in the form of facial scar deposition,
      which itself can necessitate surgical repair. This represents a substantial but
      as yet underappreciated health care burden attendant to maxillofacial injury.

PMID- 20044190
TI  - Position of mandibular canal and ramus morphology before and after sagittal split
      ramus osteotomy.
AB  - PURPOSE: The purpose of this study was to evaluate changes in the mandibular
      canal and ramus morphology before and after a sagittal split ramus osteotomy.
      PATIENTS AND METHODS: The subjects were 30 patients (60 sides) with mandibular
      prognathism who had undergone bilateral sagittal split ramus osteotomy setback
      surgery. The mandibular canal position and ramus morphology were measured at the
      3 horizontal planes under the mandibular foramen level (level A), 1 cm lower than
      level A (level B), and 2 cm lower than level A (level C) preoperatively and 1
      year postoperatively by computed tomography. RESULTS: Postoperative ramus width,
      lateral distance, lateral marrow distance, and canal length were significantly
      larger than the preoperative values at the foramen, 1 cm lower, and 2 cm lower.
      The mandibular canal completely contacted the lateral cortex without lateral bone
      marrow in 6 sides (10%) in levels A and B and 4 sides (6.7%) in level C
      preoperatively and 6 sides (10%) in level C postoperatively. CONCLUSION: This
      study suggested that postoperative mandibular canal position was located more
      posteriorly and the postoperative lateral bone marrow became thicker compared
      with the preoperative state.

PMID- 20044191
TI  - New arthroscopic disc repositioning and suturing technique for treating internal
      derangement of the temporomandibular joint: part II--magnetic resonance imaging
      evaluation.
AB  - PURPOSE: To evaluate the efficiency of an arthroscopic suturing technique for
      stabilizing anteriorly displaced discs in patients with internal derangement of
      the temporomandibular joint (TMJ) by magnetic resonance (MR) imaging. PATIENTS
      AND METHODS: Six hundred thirty-nine patients (764 joints) diagnosed as having
      stages II to V of internal derangement were treated with arthroscopic disc
      repositioning and suturing from August 2004 to March 2007. Consecutive MR images
      were used to evaluate internal derangement before and approximately 1 to 7 days
      after the operation for all 639 patients. The disc position of the TMJ was judged
      according to the success criteria, which included 3 different sagittal planes
      (lateral, central, and medial). Operative efficiency in those patients, whose
      discs of the TMJ were affirmed to be in a normal position in all 3 planes, was
      evaluated to be excellent. Those patients whose discs were in a normal position
      in 2 planes were evaluated to be good. The others were evaluated to be poor.
      Cases evaluated as excellent and good were considered success cases (if the disc
      is displaced only in 1 or 2 planes before operation, the efficiency of the
      operation would be evaluated as a success only if the whole disc was in normal
      position). RESULTS: Postoperative consecutive MR images for all 764 joints
      confirmed that 95.42% (729/764) of the joints were excellent, 3.14% (24/764) were
      good, and only 1.44% (11/764) were poor. Repeated arthroscopic surgery or open
      surgery was carried out for the joints that were evaluated as poor. CONCLUSION:
      This study indicates that the TMJ arthroscopic suturing technique is effective in
      repositioning the TMJ disc as confirmed by an MR imaging examination, but long
      term follow-up is necessary.

PMID- 20044192
TI  - Nonunion of mandibular midline osteotomy after tumor surgery and radiation
      repaired by endosseous implants.
AB  - Nonunion of the mandible after microvascular flap reconstruction of defects
      resulting from tumor surgery is a known but rare complication, occurring in 5% of
      cases. When nonunion results with the use of microvascular flaps, rigid internal
      fixation, and radiotherapy, other options to treat the nonunion carry a greater
      risk of osteomyelitis, osteoradionecrosis, and/or persistent nonunion. Although
      endosseous implants have been reported to cause mandibular fracture in some
      cases, our case proposes and supports the use of implants for immobilization
      and/or prevention of nonunion of the mandible in patients who have a high
      probability of this complication developing, thereby avoiding plating across the
      nonunion site with the risk of plate exposure and osteoradionecrosis. This
      technique permitted a good quality of life in our patient during the healing
      period. He was able to masticate and phonate properly when compared with other
      treatment options that would have required external and/or intermaxillary
      fixation devices.

PMID- 20044193
TI  - Hippocampal region-specific contributions to memory performance in normal
      elderly.
AB  - To investigate the relationship between regional hippocampal volume and memory in
      healthy elderly, 147 community-based volunteers, aged 55-83years, were evaluated
      using magnetic resonance imaging, the Groton Maze Learning Test, Visual
      Reproduction and the Rey Auditory Verbal Learning Test. Hippocampal volumes were
      determined by interactive volumetry. We found greater age-related reduction in
      the volume of the hippocampal head relative to the tail. Right hippocampal tail
      volume correlated with spatial memory on the Groton Maze Learning Test while left
      hippocampal body volume was associated with delayed verbal memory. These
      associations were independent of age, sex, education and speed of processing and
      support the notion of functional differentiation along the long axis of the
      hippocampus.

PMID- 20044194
TI  - Right-left approach and reaching arm movements of 4-month infants in free and
      constrained conditions.
AB  - Recent theories on the evolution of language (e.g. Corballis, 2009) emphazise the
      interest of early manifestations of manual laterality and manual specialization
      in human infants. In the present study, left- and right-hand movements towards a
      midline object were observed in 24 infants aged 4months in a constrained
      condition, in which the hands were maintained closed, and in a free condition. A
      left-hand dominance for approach movements without contact with the object, and a
      right-hand dominance for reaching movements with object contact was observed in
      the free condition. In the constrained condition reaching movements of the right
      hand decreased dramatically. These results are interpreted as strong evidence of
      manual specialization in 4-month olds, with approach movements having a
      localization role and reaching movements announcing future right-hand dominance
      for prehension and object manipulation.

PMID- 20044195
TI  - [Starling-induced hypersensitivity pneumonitis: minimal but persistent antigen
      exposure].
AB  - A 51-year old woman developed hypersensitivity pneumonitis (HP) after inhaling
      the excrement of starlings that populated a park adjacent to her home. The
      clinical symptoms consisted of a non-productive cough and grade II dyspnea and
      radiological interstitial micronodular involvement. The respiratory function
      tests showed a restrictive pattern with desaturation on effort and a biopsy using
      videothorascopy was highly suggestive of HP. After taking a very detailed
      clinical history the patient mentioned an increase in cough when she crossed a
      park near her home, where a high population of starlings lived in its trees.
      Specific antigen extracts were prepared and skin tests were performed,
      precipitins measured, and bronchial provocation tests specific to this antigen
      were all positive. This observation identified a species of bird capable of
      causing the disease and shows a lung disease secondary to the exposure of a not
      very large but persistent antigen load.

PMID- 20044196
TI  - [Organizing pneumonia associated with psoriasis].

PMID- 20044197
TI  - A study of the bibliometry and areas of the research groups of Archivos de
      Bronconeumologia (2003-2007).
AB  - INTRODUCTION: Scientific cooperation is essential for the advance of biomedical
      research. Scientists set up informal groups to work together on common issues,
      who are the main units in the research funding system. Bibliometric and Social
      Network Analysis methods allow informal groups in scientific papers to be
      identified and characterised. The objective of the study is to identify research
      groups in Archivos de Bronconeumologia between 2003 and 2007 period with the aim
      of characterizing their scientific collaboration patterns and research areas.
      METHODS: Co-authorships, institutional collaboration relationships and the main
      research areas of papers published in Archivos de Bronconeumologia have been
      identified. Co-authorship networks and institutional collaboration networks have
      been constructed by using Pajek software tool. RESULTS: A total of 41 research
      groups involving 171 investigators have been identified. The Collaboration Index
      for articles was 5.59 and the Transcience Index was 73.11%. There was
      institutional collaboration in 60.33% of papers. The collaboration between
      institutions of the same region prevails (41.03%), followed by collaborations
      between departments, services or units of the same institution (39.74%), inter
      regional collaboration (14,97%) and international collaboration (6.83%). A total
      of 83.03% of articles were cited. The main research areas covered by groups were
      chronic obstructive pulmonary disease, asthma, lung neoplasm, bronchogenic
      carcinoma, smoking and pulmonary embolism. CONCLUSIONS: The scientific production
      of a large number of Respiratory System Spanish research groups is published in
      Archivos de Bronconeumologia. A notable collaboration and citation rate has been
      observed. Nevertheless, it is still essential to encourage inter-regional and
      international collaboration.

PMID- 20044198
TI  - Performance of chest compressions by laypersons during the Public Access
      Defibrillation Trial.
AB  - BACKGROUND: Increasing evidence indicates that health professionals often may not
      achieve guideline standards for cardiopulmonary resuscitation (CPR). Little is
      known about layperson CPR performance. METHODS: The investigation was a
      retrospective cohort study of cardiac arrest patients treated by layperson CPR
      and one model of automated external defibrillator (AED) as part of the Public
      Access Defibrillation Trial (n=26). CPR was measured using software that
      integrates the event log, ECG signal, and thoracic impedance signal. We assessed
      chest compression fraction (proportion of attempted resuscitation spent
      performing chest compressions), prompted compression fraction (proportion of
      attempted resuscitation spent performing compressions during AED-prompted
      periods), compression rate, and compressions per minute. RESULTS: Of the 26
      cases, 13 presented with ventricular fibrillation and 13 with nonshockable
      rhythms. Overall, during the period when patients did not have spontaneous
      circulation, the median chest compression fraction was 34% (IQR 17-48%), median
      prompted chest compression fraction was 49% (IQR 30-66%), and the median chest
      compression rate was 96/min (IQR 90-110/min). Taken together, the median chest
      compression delivered per minute among all arrests was 29 (IQR 20-42). CPR
      characteristics differed according to initial rhythm: median chest compression
      per minute was 20 (IQR 13-29) among ventricular fibrillation and 42 (IQR 28-47)
      among nonshockable rhythms (p=0.003). CONCLUSIONS: In this study of trained
      laypersons, CPR varied substantially and often did not achieve guideline
      parameters. The findings suggest a need to improve CPR training, consider changes
      to CPR protocols, and/or improve the AED-rescuer interface.

PMID- 20044199
TI  - The effectiveness of a procedure is dependent on the willingness of people to
      actually do the procedure.

PMID- 20044202
TI  - Estimating the economic value of ice climbing in Hyalite Canyon: An application
      of travel cost count data models that account for excess zeros.
AB  - Recently, the sport of ice climbing has seen a dramatic increase in popularity.
      This paper uses the travel cost method to estimate the demand for ice climbing in
      Hyalite Canyon, Montana, one of the premier ice climbing venues in North America.
      Access to Hyalite and other ice climbing destinations have been put at risk due
      to liability issues, public land management agendas, and winter road conditions.
      To this point, there has been no analysis on the economic benefits of ice
      climbing. In addition to the novel outdoor recreation application, this study
      applies econometric methods designed to deal with "excess zeros" in the data.
      Depending upon model specification, per person per trip values are estimated to
      be in the range of $76 to $135.

PMID- 20044200
TI  - Perfluorocarbon induced intra-arrest hypothermia does not improve survival in a
      swine model of asphyxial cardiac arrest.
AB  - BACKGROUND: Pulseless electrical activity is an important cause of cardiac
      arrest. Our purpose was to determine if induction of hypothermia with a cold
      perfluorocarbon-based total liquid ventilation (TLV) system would improve
      resuscitation success in a swine model of asphyxial cardiac arrest/PEA. METHODS:
      Twenty swine were randomly assigned to control (C, no ventilation, n=11) or TLV
      with pre-cooled PFC (n=9) groups. Asphyxia was induced by insertion of a stopper
      into the endotracheal tube, and continued in both groups until loss of aortic
      pulsations (LOAP) was reached, defined as a pulse pressure less than 2mmHg. The
      TLV animals underwent asphyxial arrest for an additional 2min after LOAP,
      followed by 3min of hypothermia, prior to starting CPR. The C animals underwent
      5min of asphyxia beyond LOAP. Both groups then underwent CPR for at least 10min.
      The endpoint was the resumption of spontaneous circulation maintained for 10min.
      RESULTS: Seven of 9 animals achieved resumption of spontaneous circulation (ROSC)
      in the TLV group vs. 5 of 11 in the C group (p=0.2). The mean pulmonary arterial
      temperature was lower in total liquid ventilation animals starting 4min after
      induction of hypothermia (TLV 36.3+/-0.2 degrees C vs. C 38.1+/-0.2 degrees C,
      p<0.0001). Arterial P(O)(2) was higher in total liquid ventilation animals at
      2.5min of CPR (TLV 76+/-12mmHg vs. C 44+/-2mmHg; p=0.03). CONCLUSION: Induction
      of moderate hypothermia using perfluorocarbon-based total liquid ventilation did
      not improve ROSC success in this model of asphyxial cardiac arrest.

PMID- 20044203
TI  - Adsorption characterization of Pb(II) and Cu(II) ions onto chitosan
      tripolyphosphate beads: Kinetic, equilibrium and thermodynamic studies.
AB  - Chitosan-tripolyphosphate (CTPP) beads were synthesized, characterized and were
      used for the adsorption of Pb(II) and Cu(II) ions from aqueous solution. The
      effects of initial pH, agitation period, adsorbent dosage, different initial
      concentrations of heavy metal ions and temperature were studied. The experimental
      data were correlated with the Langmuir, Freundlich and Dubinin-Radushkevich
      isotherm models. The maximum adsorption capacities of Pb(II) and Cu(II) ions in a
      single metal system based on the Langmuir isotherm model were 57.33 and 26.06
      mg/g, respectively. However, the beads showed higher selectivity towards Cu(II)
      over Pb(II) ions in the binary metal system. Various thermodynamic parameters
      such as enthalpy (DeltaH degrees), Gibbs free energy (DeltaG degrees) and entropy
      (DeltaS degrees) changes were computed and the results showed that the adsorption
      of both heavy metal ions onto CTPP beads was spontaneous and endothermic in
      nature. The kinetic data were evaluated based on the pseudo-first and -second
      order kinetic and intraparticle diffusion models. Infrared spectra were used to
      elucidate the mechanism of Pb(II) and Cu(II) ions adsorption onto CTPP beads.

PMID- 20044204
TI  - Distribution of the high-affinity binding site and intracellular target of
      botulinum toxin type A in the human bladder.
AB  - BACKGROUND: Botulinum toxin type A (BoNTA) has been successfully used in the
      treatment of refractory detrusor overactivity. The toxin is internalized after
      binding a high-affinity receptor, synaptic vesicle protein 2 (SV2), which is
      exposed in the cell membrane during the exocytosis process. In the cytoplasm,
      BoNTA cleaves specific sites of synaptosomal-associated protein 25 (SNAP-25),
      preventing the assembly of the synaptic fusion complex SNARE and blocking
      exocytosis. OBJECTIVE: In the present work, the distribution of SV2 and SNAP-25
      was first investigated in human bladders. The neurochemistry of BoNTA-sensitive
      structures was then investigated using markers for parasympathetic, sympathetic,
      and sensory fibers. DESIGN, SETTING, AND PARTICIPANTS: Human bladders were
      obtained from cadaveric organ donors (age range: 19-74 yr). MEASUREMENTS: Bladder
      sections were processed for single or dual immunofluorescence staining with
      antibodies against SV2, SNAP-25, beta-3 tubulin, vesicular acetylcholine
      transporter, tyrosine hydroxilase, and calcitonin gene-related peptide. RESULTS
      AND LIMITATIONS: SV2 and SNAP-25 immunoreactive fibers were distributed
      throughout the suburothelium and muscular layer. Double labeling showed extensive
      colocalization of both proteins in nerve fibers. SV2 is more expressed in
      parasympathetic fibers than in sympathetic or sensory fibers. No expression was
      found in urothelial or muscular cells. Because only normal bladders were used,
      this distribution should be applied with caution to pathologic bladders.
      CONCLUSIONS: SV2 and SNAP-25 colocalize abundantly throughout the urinary
      bladder. SV2 is more abundant in cholinergic, parasympathetic fibers. These
      nerves are suggested to be the main target for BoNTA action in the human urinary
      bladder.

PMID- 20044205
TI  - Induction of neuronal apoptosis inhibitory protein expression in response to
      androgen deprivation in prostate cancer.
AB  - A mechanism for survival of prostate cancer cells in an androgen-deprived
      environment remains elusive. Here, we find that expression of neuronal apoptosis
      inhibitory protein (NAIP) was significantly increased in vivo and in vitro in
      response to androgen deprivation therapy (ADT). Increased expression of NAIP
      corresponded to increased DNA-binding activity of NF-kappaB that physically
      associated to previously uncharacterized kappaB-like sites in the NAIP locus.
      Importantly, expression of NAIP was significantly increased (p=0.04) in clinical
      samples of prostate cancer from patients receiving ADT. Expression of NAIP may be
      associated with enhanced survival of prostate cancer in response to castration.

PMID- 20044206
TI  - An external domino effects investment approach to improve cross-plant safety
      within chemical clusters.
AB  - Every company situated within a chemical cluster faces the risk of being struck
      by an escalating accident at one of its neighbouring plants (the so-called
      external domino effect risks). These cross-plant risks can be reduced or
      eliminated if neighbouring companies are willing to invest in systems and
      measures to prevent them. However, since reducing such multi-plant risks does not
      lead to direct economic benefits, enterprises tend to be reluctant to invest more
      than needed for meeting minimal legal requirements and they tend to invest
      without collaborating. The suggested approach in this article indicates what
      information is required to evaluate the available investment options in external
      domino effects prevention. To this end, game theory is used as a promising
      scientific technique to investigate the decision-making process on investments in
      prevention measures simultaneously involving several plants. The game between two
      neighbouring chemical plants and their strategic investment behaviour regarding
      the prevention of external domino effects is described and an illustrative
      example is provided. Recommendations are formulated to advance cross-plant
      prevention investments in a two-company cluster.

PMID- 20044207
TI  - Adsorption of methylene blue on low-cost adsorbents: a review.
AB  - In this article, the use of low-cost adsorbents for the removal of methylene blue
      (MB) from solution has been reviewed. Adsorption techniques are widely used to
      remove certain classes of pollutants from waters, especially those which are not
      easily biodegradable. The removal of MB, as a pollutant, from waste waters of
      textile, paper, printing and other industries has been addressed by the
      researchers. Currently, a combination of biological treatment and adsorption on
      activated carbon is becoming more common for removal of dyes from wastewater.
      Although commercial activated carbon is a preferred adsorbent for color removal,
      its widespread use is restricted due to its relatively high cost which led to the
      researches on alternative non-conventional and low-cost adsorbents. The purpose
      of this review article is to organize the scattered available information on
      various aspects on a wide range of potentially low-cost adsorbents for MB
      removal. These include agricultural wastes, industrial solid wastes, biomass,
      clays minerals and zeolites. Agricultural waste materials being highly efficient,
      low cost and renewable source of biomass can be exploited for MB remediation. It
      is evident from a literature survey of about 185 recently published papers that
      low-cost adsorbents have demonstrated outstanding removal capabilities for MB.

PMID- 20044208
TI  - Demonstration of differences in virulence between two Theileria parva isolates.
AB  - In areas with a low incidence of infection due to unimodal presence of ticks,
      Theileria parva has been observed to induce a disease with relatively low
      pathology. This is followed by a carrier state, rather than death and therefore
      provides a better chance of transmission of the parasite back to the tick vector
      since in unimodal conditions, the different tick stages occur at different times.
      One isolate from such an area in Zambia, T. parva Chitongo, was compared for
      virulence with T. parva Muguga, isolated from an area exhibiting a continuous
      presence of all vector stages in East Africa. To reduce any variation due to
      infection dose, an in vitro standardized dose was used to initiate infection of
      groups of three local zebu cattle with each isolate. Parameters of virulence
      measured were prepatent period, fever, survival (based on ECF index),
      parasitosis, piroplasm parasitaemia and hematological parameters. Our results
      suggest that T. parva Chitongo developed a slightly later onset (1-2 days) and
      lower levels of parasitosis in the lymph node, causing less and later mortality.
      Comparison of the in vitro rate of transformation confirmed that the time needed
      to transform an infected lymphocyte took 4 days longer for T. parva Chitongo than
      T. parva Muguga. Elucidating the mechanism responsible for the lower virulence of
      T. parva Chitongo could be useful for designing an attenuated vaccine.

PMID- 20044209
TI  - Combined treatment with cytoprotective agents and radiotherapy.
AB  - Radiotherapy is associated with several toxicities affecting healthy tissues. One
      of the strategies aimed at decreasing radiation toxicity is the use of
      radioprotective agents, such as amifostine and palifermin, or factors stimulating
      hemopoetic stem cells (colony stimulating factors, CSFs): granulocyte-CSF,
      granulocyte macrophage-CSF and recombinant erythropoetins. The potential
      beneficial effect of these substances demonstrated in preclinical in vitro and in
      vivo studies led to numerous clinical trials. This review addresses the current
      experience on the use of cytoprotective agents in combination with radiotherapy,
      with particular focus on the safety of these approaches. Despite a relatively
      large body of literature data, the role of cytoprotective agents combined with
      radiotherapy remains controversial. Overall, their use in this application is
      still limited due to modest radioprotective effect for normal tissues, potential
      risk of tumor protection and increased treatment toxicity. The use of
      erythropoetins in combination with radiotherapy should generally be discouraged,
      whereas the safe and effective application of other agents warrants further
      investigations.

PMID- 20044210
TI  - Disgust affects TNF-alpha, IL-6 and noradrenalin levels in patients with
      obsessive-compulsive disorder.
AB  - Neurobiological research of obsessive-compulsive disorder (OCD) has rarely taken
      in account the context dependent evocation of obsessive-compulsive symptoms. To
      bypass this obstacle, this study investigated neurobiological parameters during a
      standardized disgust provocation paradigm in patients with OCD and healthy
      controls. Ten OCD patients and 10 healthy controls were exposed to 9 disgust
      related items using a standardized provocation paradigm. Catecholamines and
      cortisol in plasma and lipopolysaccharide (LPS) stimulated levels of TNF-alpha
      and IL-6 by peripheral leucocytes were assessed along with severity of obsessive
      compulsive symptoms, disgust, and anxiety levels using Visual Analogue Scales
      prior, during and after a provocation paradigm. Noradrenalin levels increased,
      while LPS stimulated TNF-alpha and IL-6 by peripheral leucocytes decreased during
      exposure to disgust related objects in OCD patients but not in healthy controls.
      Cortisol levels were not affected by exposure neither in patients nor in
      controls, but overall cortisol levels of OCD patients were increased compared to
      controls. In conclusion, our data suggests that symptom provocation in OCD
      patients with contamination fear is accompanied by alterations in the immune and
      neuroendocrine systems but does not affect cortisol levels.

PMID- 20044211
TI  - Increased parasympathetic tone as the underlying cause of asthma: a hypothesis.
AB  - Asthma is a chronic inflammatory disease of airways that is characterized by
      increased responsiveness of the tracheo-bronchial tree to multiple number of
      stimuli. Immunological theory does not explain all features in asthma, for
      example hyper-reactivity of the airways. Neurogenic theory also fails to explain
      the pathogenesis of asthma comprehensively. Higher parasympathetic tone has been
      reported in asthmatics but has never been suggested as a major underlying cause
      of asthma. This article attempts to explain the occurrence of hyper
      responsiveness, inflammatory/allergic reactions and broncho-constriction in
      asthma on a common basis of inherent higher parasympathetic tone in asthmatics.
      The higher background parasympathetic firing leads to increased nitric oxide (NO)
      production owing to its co-localization with acetylcholine (ACh) in inhibitory
      non-adrenergic and non-cholinergic (i-NANC) nerves. NO is a neurotransmitter of i
      NANC system and it mediates bronchodilation. Increased NO release has been found
      to be responsible for hyper-responsiveness and increased inflammation in the
      airways. The authors suggest that an inherently higher background parasympathetic
      tone in concert with inflammation or a specific genetic background could modify
      the effects of NO on lung homeostasis in humans leading to increased
      susceptibility to an asthmatic state.

PMID- 20044212
TI  - The resonance theory of coronary arterial wall stress as an explanation for the
      distribution of coronary artery disease.
AB  - The coronary arteries are unique within the arterial system in being subject to a
      continuous oscillatory displacement. It is hypothesised that oscillatory
      resonance of the coronary arteries occurs when the heart rate is the same as the
      arteries' Natural Frequency of oscillation. If resonance were to occur then
      standing waves would exist along the coronary arteries. The sites of the anti
      nodes of such standing waves would be the sites of increased wall stress and
      therefore be expected to be predisposed to disease. Coronary artery resonance
      would explain the observed increased incidence of disease in the proximal
      segments of the arteries. It is proposed that coronary artery resonance is a
      previously unrecognised aetiological factor for coronary artery disease that
      contributes to its location. If the hypothesis is true then there are potential
      important consequences for the diagnosis and treatment of the disease.

PMID- 20044213
TI  - Natural cocoa as diet-mediated antimalarial prophylaxis.
AB  - BACKGROUND: The Maya of Central America are credited with the first consumption
      of cocoa and maintaining its ancient Olmec name kakawa translated in English as
      "God Food", in recognition of its multiple health benefits. The legend of cocoa
      is receiving renewed attention in recent years, on account of epidemiological and
      scientific studies that support its cardiovascular health benefits. Increasing
      numbers of scientific reports corroborating cocoa's antiquated reputation as
      health food persuaded this author to promote regular consumption of cocoa in
      Ghana since 2004. Cocoa is readily available in Ghana; the country is the second
      largest producer accounting for 14% of the world's output. Numerous anecdotal
      reports of reduced episodic malaria in people who daily drink natural unsweetened
      cocoa beverage prompted a search for scientific mechanisms that possibly account
      for cocoa's antimalarial effects. This paper presents the outcome as a
      hypothesis. METHODS: Internet search for literature on effects of cocoa's
      ingredients on malaria parasites and illness using a variety of search tools.
      RESULTS: Evidential literature suggests five mechanisms that possibly underpin
      cocoa's anecdotal antimalarial effects. (i) Increased availability of
      antioxidants in plasma, (ii) membrane effects in general and erythrocyte membrane
      in particular, (iii) increased plasma levels of nitric oxide, (iv) antimalarial
      activity of cocoa flavanoids and their derivatives, and (v) boosted immune system
      mediated by components of cocoa including cocoa butter, polyphenols, magnesium,
      and zinc. CONCLUSION: A hypothesis is formulated that cocoa offers a diet
      mediated antimalarial prophylaxis; and an additional novel tool in the fight
      against the legendary scourge.

PMID- 20044214
TI  - Radiotherapy treatment plans with RapidArc for prostate cancer involving seminal
      vesicles and lymph nodes.
AB  - PURPOSE: Dosimetric results and treatment delivery efficiency of RapidArc plans
      to those of conventional intensity-modulated radiotherapy (IMRT) plans were
      compared using the Eclipse treatment planning system for high-risk prostate
      cancer. MATERIALS AND METHODS: This study included 10 patients. The primary
      planning target volume (PTV(P)) contained prostate, seminal vesicles, and pelvic
      lymph nodes with a margin. The boost PTV (PTV(B)) contained prostate and seminal
      vesicles with a margin. The total prescription dose was 75.6 Gy (46.8 Gy to
      PTV(P) and an additional 28.8 Gy to PTV(B); 1.8 Gy/fraction). Three plans were
      generated for each PTV: Multiple-field IMRT, one-arc RapidArc (1ARC), and two-arc
      RapidArc (2ARC). RESULTS: In the primary IMRT with PTV(P), average mean doses to
      bladder, rectum and small bowel were lower by 5.9%, 7.7% and 4.3%, respectively,
      than in the primary 1ARC and by 3.6%, 4.8% and 3.1%, respectively, than in the
      primary 2ARC. In the boost IMRT with PTV(B), average mean doses to bladder and
      rectum were lower by 2.6% and 4.8% than with the boost 1ARC and were higher by
      0.6% and 0.2% than with the boost 2ARC. Integral doses were 7% to 9% higher with
      RapidArc than with IMRT for both primary and boost plans. Treatment delivery time
      was reduced by 2-7 minutes using RapidArc. CONCLUSION: For PTVs including
      prostate, seminal vesicles, and lymph nodes, IMRT performed better in dose
      sparing for bladder, rectum, and small bowel than did RapidArc. For PTVs
      including prostate and seminal vesicles, RapidArc with two arcs provided plans
      comparable to those for IMRT. The treatment delivery is more efficient with
      RapidArc.

PMID- 20044215
TI  - Is elective irradiation to the lower neck necessary for N0 nasopharyngeal
      carcinoma?
AB  - PURPOSE: To summarize our experience and treatment results in lymph node-negative
      nasopharyngeal carcinoma treated in a single institution. METHODS AND MATERIALS:
      From January 2000 to December 2003, 410 patients with lymph node-negative
      nasopharyngeal carcinoma were retrospectively analyzed. The T-stage distribution
      was 18.8% in T1, 54.6% in T2 (T2a, 41 patients; T2b, 183 patients), 13.2% in T3,
      and 13.4% in T4. All patients received radiotherapy to the nasopharynx, skull
      base, and upper neck drainage areas, including levels II, III, and VA. The dose
      was 64-74 Gy, 1. 8-2.0 Gy per fraction over 6.5-7.5 weeks to the primary tumor
      with (60)Co or 6-MV X-rays, and 50-56 Gy to levels II, III, and VA. Residual
      disease was boosted with either (192)Ir afterloading brachytherapy or small
      external beam fields. RESULTS: The median follow-up time was 54 months (range, 3
      90 months). Four patients developed neck recurrence, and only 1 patient (0.2%)
      experienced relapse outside the irradiation fields. The 5-year overall survival
      rate was 84.2%. The 5-year relapse-free survival rate, distant metastasis-free
      survival rate, and disease-free survival rate were 88.6%, 90.6% and 80.1%,
      respectively. Both univariate and multivariate analyses demonstrated that T
      classification was the only significant prognostic factor for predicting overall
      survival. The observed serious late toxicities were radiation-induced brain
      damage (7 cases), cranial nerve palsy (16 cases), and severe trismus (13 cases;
      the distance between the incisors was < or = 1 cm). CONCLUSION: Elective levels
      II, III, and VA irradiation is suitable for nasopharyngeal carcinoma without neck
      lymph node metastasis.

PMID- 20044216
TI  - Young men have equivalent biochemical outcomes compared with older men after
      treatment with brachytherapy for prostate cancer.
AB  - PURPOSE: To evaluate retrospectively the biochemical outcomes of young men
      treated with low-dose-rate brachytherapy for prostate cancer. METHODS AND
      MATERIALS: From 1990 to 2005, 1,665 men with clinically localized prostate cancer
      were treated with low-dose-rate brachytherapy +/- hormone therapy (HT) +/-
      external beam radiotherapy and underwent > or = 2 years of follow-up. Patients
      were stratified on the basis of age: < or = 60 (n = 378) and >60 years (n =
      1,287). Biochemical failure was defined as a prostate-specific antigen (PSA)
      nadir plus 2 ng/mL. Univariate and multivariate analyses were used to determine
      the association of variables with freedom from biochemical failure (FFbF).
      RESULTS: Median follow-up was 68 months (range, 24-180) for men < or = 60 years
      and 66 months (range, 24-200) for men >60. For the entire group, the actuarial 5-
      and 8-year FFbF rates were 94% and 88%, respectively. Men < or = 60 demonstrated
      similar 5- and 8-year FFbF (95% and 92%) compared with men >60 (93% and 87%; p =
      0.071). A larger percent of young patients presented with low-risk disease; lower
      clinical stage, Gleason score (GS), and pretreatment PSA values; were treated
      after 1997; did not receive any HT; and had a high biologic effective dose (BED)
      of radiation (all ps <0.001). On multivariate analysis, PSA (p = 0.001), GS (p =
      0.005), and BED (p < 0.001) were significantly associated with FFbF, but age was
      not (p = 0.665). CONCLUSION: Young men achieve excellent 5- and 8-year
      biochemical control rates that are comparable to those of older men after
      prostate brachytherapy. Young age should not be a deterrent when considering
      brachytherapy as a primary treatment option for clinically localized prostate
      cancer.

PMID- 20044217
TI  - Cognitive function before and after intensity-modulated radiation therapy in
      patients with nasopharyngeal carcinoma: a prospective study.
AB  - PURPOSE: To evaluate the effects of radiation therapy (RT) on neurocognitive
      function in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS:
      Thirty patients with NPC treated with intensity-modulated RT were included. Dose
      volume histograms of the temporal lobes were obtained in every patient.
      Neurocognitive tests were administered individually to each patient 1 day before
      initiation of RT and at least 12 months after completion of RT. Cognitive
      functioning status was evaluated as change in scores over time. RESULTS: Among
      the total of 30 patients, 23 patients (76.7%) had significantly lower post-RT
      cognitive functioning scores compared with their pre-RT scores (p = 0.033). The
      cognitive functioning scores had significantly declined in the domains of short
      term memory, language abilities, and list-generating fluency (p = 0.020, 0.023,
      and 0.001, respectively). Compared with patients with a mean dose to the temporal
      lobes of 36 Gy or less, patients with a mean dose of greater than 36 Gy had a
      significantly greater reduction in cognitive functioning scores (p = 0.017).
      Patients in whom V60 of the temporal lobes (i.e., the percentage of the temporal
      lobe volume that had received >60 Gy) was greater than 10% also had a greater
      reduction in cognitive functioning scores than those in whom V60 was 10% or less
      (p = 0.039). CONCLUSIONS: The results of our study indicated that RT could have
      deleterious effects on cognitive function in patients with NPC. Efforts should be
      made to reduce the radiation dose and irradiated volume of temporal lobes without
      compromising the coverage of target volume.

PMID- 20044218
TI  - Reduction in radiation-induced morbidity by use of an intercurrent boost in the
      management of early-stage breast cancer.
AB  - PURPOSE: Electron or photon boost immediately following whole-breast irradiation
      performed after conservation surgery for early-stage breast cancer is the
      accepted standard of care. This regimen frequently results in Grade III
      dermatitis, causing discomfort or treatment interruption. Herein, we compare
      patients treated with whole-breast irradiation followed by boost compared with a
      cohort with a planned intercurrent radiation boost. METHODS AND MATERIALS: The
      records of 650 consecutive breast cancer patients treated at Allegheny General
      Hospital (AGH) between 2000 and 2008 were reviewed. Selected for this study were
      327 patients with T1 or T2 tumors treated with external beam radiotherapy
      postlumpectomy. One hundred and sixty-nine patients were treated by whole-breast
      radiotherapy (WBRT) followed by boost at completion. One hundred fifty-eight were
      treated with a planned intercurrent boost (delivered following 3,600 cGy WBRT).
      The mean whole breast radiation dose in the conventionally treated group was
      5,032 cGy (range, 4500-5400 cGy), and the mean whole breast dose was 5,097 cGy
      (range, 4860-5040 cGy) in the group treated with a planned intercurrent boost.
      RESULTS: The occurrence of Grade III dermatitis was significantly reduced in the
      WBRT/intercurrent boost group compared with the WBRT/boost group (0.6% vs. 8.9%),
      as was the incidence of treatment interruption (1.9% vs. 14.2%). With a median
      follow-up of 32 months and 27 months, respectively, no significant difference in
      local control was identified. CONCLUSIONS: Patients treated with intercurrent
      boost developed less Grade III dermatitis and unplanned treatment interruptions
      with similar local control.

PMID- 20044219
TI  - Differential activation of the Toll-like receptor 2/6 complex by lipoproteins of
      Streptococcus suis serotypes 2 and 9.
AB  - Streptococcus suis causes invasive infections in pigs and occasionally in humans.
      Worldwide, S. suis serotype 2 is most frequently isolated from diseased piglets,
      but the less virulent serotype 9 is emerging, at least in Europe. We compared the
      activation of human Toll-like receptors (hTLRs) by S. suis serotype 2 and 9
      strains to better understand the role of the innate immune response in fighting
      S. suis infections. Neither live nor heat-killed log phase grown S. suis
      activated the hTLR1/2, hTLR2/6 and hTLR4/MD-2 complexes. However, the hTLR2/6
      complex was specifically activated by both serotypes after disruption of the cell
      wall synthesis using penicillin. Activation levels of the hTLR2/6 complex were
      higher for serotype 9 strains compared to serotype 2 strains suggesting intrinsic
      differences in cell wall composition between both serotypes. The hTLR2/6
      activating fractions decreased in molecular size after digestion with proteinase
      K and were sensitive for lipoprotein lipase digestion and NaOH hydrolysis,
      indicating lipoprotein(s) as active component(s). Overall, our results indicate
      that S. suis lipoproteins activate TLR2/6 but not TLR1/2 and that the clinically
      different serotypes 2 and 9 display differential release of TLR ligand when cell
      wall integrity is compromised.

PMID- 20044220
TI  - Isolation and characterization of feline panleukopenia virus from a diarrheic
      monkey.
AB  - A feline panleukopenia virus (FPV) mutant, monkey/BJ-22/2008/CHN, was isolated
      from intestinal contents of a diarrheic monkey in Beijing, China. The virus was
      identified by morphology and physicochemical characteristics, and specific
      fragments were obtained by PCR using consensus primers of parvovirus and specific
      primers of FPV. Sequence of the full-length VP2 gene of the isolated FPV was
      determined and analyzed by comparison with reference FPV and canine parvovirus
      (CPV) isolates, showing high homology with FPV (98.75%) and CPV (98.15%).
      Phylogenetic analysis indicated that the isolated FPV formed a monophyletic
      branch in FPV cluster which differed from the other 11 FPV isolates from China
      and other countries. The isolated virus caused typical clinical symptoms of FPV
      in cats. This is the first report on isolation of FPV from a monkey.

PMID- 20044222
TI  - Management of obesity in menopause: diet, exercise, pharmacotherapy and bariatric
      surgery.
AB  - Menopause is characterized by the progressive reduction of estrogens resulting to
      cessation of menses. It is associated with an increase of cardiovascular risk
      factors such as hyperglycemia, hypertension, dyslipidemia and of abdominal and/or
      selective visceral fat mass deposition. Obesity, a modern day epidemic, is
      promoted by an obesogenic environment that interacts with the genetic background.
      The result is a positive energy balance materialized by the accumulation of the
      adipose tissue. This process is marked by great individual variation. Obesity is
      also associated with the presence of cardiovascular risk factors. In this review,
      the main pathophysiologic processes for the increase of obesity in menopause and
      the possible effects of pre-menopausal obesity regarding the cessation of ovarian
      function are described. The interactions among the hypothalamic-pituitary-gonadal
      and -adrenal (stress system) axes and the environment are explored. Furthermore,
      the therapeutic means that a clinician can employ to help menopausal women to
      overcome the menopause-associated increase of their weight are developed.

PMID- 20044221
TI  - Midlife predictors of Alzheimer's disease.
AB  - Factors contributing to increased risk for Alzheimer's disease (AD) include age,
      sex, genes, and family history of AD. Several risk factors for AD are endogenous;
      however, accumulating evidence implicates modifiable risk factors in the
      pathogenesis of AD. Although the continued task of identifying new genes will be
      critical to learning more about the disease, several research findings suggest
      that potentially alterable environmental factors influence genetic contributions,
      providing targets for disease prevention and treatment. Here, we review midlife
      risk factors for AD, and address the potential for therapeutic intervention in
      midlife.

PMID- 20044223
TI  - How promptly do blowflies colonise fresh carcasses? A study comparing indoor with
      outdoor locations.
AB  - We investigated the time taken by blowflies to find and oviposit on fresh
      carcasses placed outdoors and indoors. Paired dead piglets, one in the open and
      the other in a nearby room (on the first floor of an occupied, detached, suburban
      house near Cologne, Germany, with a window opened 9 cm) were exposed
      simultaneously on nine occasions. The species visiting both locations and the
      number of egg batches deposited by blowflies between both locations were
      monitored 2, 8, 24 and 48 h after exposure. In all cases the indoor piglet
      carcass was exclusively infested by Calliphora vicina; only in one case, on a
      very hot day after a 48-h exposure did Lucilia sericata infest an indoor carcass.
      The outdoor piglets were infested by a variety of common corpse-visiting species:
      L. sericata, L. caesar, L. illustris, C. vicina and C. vomitoria. A significant
      difference in the number of egg batches was detected between indoors and
      outdoors. Furthermore, in only two of nine runs did oviposition occur within the
      first 24h of exposure indoors. Ambient temperature, daylength and rainfall had no
      significant effect on the number of egg batches. Moreover, we observed fewer
      larvae on indoor piglets, too few to form maggot masses. This might result in
      slower larval development than in the case of outdoor piglets. We conclude that
      post-mortem interval (PMI) estimation for corpses found indoors must be handled
      carefully as oviposition might have taken place with a delay up to 24h.

PMID- 20044224
TI  - Detection of piperonal emitted from polymer controlled odor mimic permeation
      systems utilizing Canis familiaris and solid phase microextraction-ion mobility
      spectrometry.
AB  - Currently, in the field of odor detection, there is generally a wider variation
      in limit of detections (LODs) for canines than instruments. The study presented
      in this paper introduces an improved protocol for the creation of controlled odor
      mimic permeation system (COMPS) devices for use as standards in canine training
      and discusses the canine detection thresholds of piperonal, a starting material
      for the illicit drug 3,4-methylenedioxymethamphetamine (MDMA), when exposed to
      these devices. Additionally, this paper describes the first-ever reported direct
      comparison of solid phase microextraction-ion mobility spectrometry (SPME-IMS) to
      canine detection for the MDMA odorant, piperonal. The research presented shows
      the reliability of COMPS devices as low cost field calibrants providing a wide
      range of odorant concentrations for biological and instrumental detectors. The
      canine LOD of piperonal emanating from the 100 ng s(-1) COMPS was found to be 1
      ng as compared to the SPME-IMS LOD of piperonal in a static, closed system at 2
      ng, with a linear dynamic range from 2 ng to 11 ng. The utilization of the COMPS
      devices would allow for training that will reduce the detection variability
      between canines and maintain improved consistency for training purposes. Since
      both SPME and IMS are field portable technologies, it is expected that this
      coupled method will be useful as a complement to canine detection for the field
      detection of MDMA.

PMID- 20044225
TI  - Is developmental neuropathology of the motor neurons the key to resolving the
      mystery in motor neuron diseases?
AB  - Recently, genetic analyses on motor neurons diseases have advanced leaps and
      bounds, but mysteries still remain in the pathogenesis of amyotrophic lateral
      sclerosis and spinal muscular atrophy. Three papers in this issue of Brain and
      Development presented intriguing topics on the developmental neuropathology of
      motor neurons in the spinal cord and brainstem. Neonatal asphyxia experiments in
      rats indicated the modification of brainstem monoaminergic neuron systems in the
      development and repair of spinal motor neurons. In the victims of sudden
      perinatal and infant death, population changes in motor neurons and interneurons
      in the hypoglossal nucleus were shown to be involved in the disturbed maturation
      of the respiratory network in the brainstem. The coexistence of hypoglossal
      hypoplasia and hyperplasia of the area postrema was reported in a case of
      perinatal hypoxic ischemic encephalopathy. These findings are likely to be a key
      to resolving the undetermined pathological mechanisms of motor neuron diseases.

PMID- 20044226
TI  - [Pacemaker and implantable cardioverter defibrillator infections].
AB  - The complications of pacemaker or defibrillator implantation include a wide range
      of infections, most often with severe consequences. The incidence of these
      infections is likely to increase regularly over the next decades because of the
      increasing number of long-term cardiac devices implanted every year in developed
      countries. An infection of the generator site is most often easy to diagnose, but
      endovascular infections including infective endocarditis may remain unnoticed
      over prolonged period of time, due to the scarcity of specific symptoms. The
      microbiological diagnosis is usually made on culture with sample smears from the
      generator pocket, the device itself, and blood. The diagnosis for endocarditis
      and endovascular lead infections relies on transesophageal echocardiography,
      since transthoracic echocardiography has a very low sensitivity (less than 30%).
      The treatment invariably requires complete removal of infected device, whatever
      the clinical presentation. Recently, guidelines for diagnosis and treatment of
      pacemaker/defibrillator-related infections have been published. However, because
      the risk of hematogenous seeding to the lead is difficult to estimate, there is
      no consensus for the management of patients with bloodstream infections not
      clearly related to the device.

PMID- 20044227
TI  - [Unexpected increase of human and animal tularemia cases during winter 2007/2008
      in France: Emergence or short-lasting episode?].
AB  - CONTEXT: Tularemia is a zoonosis affecting humans and hares in France. We
      describe the results of surveillance in both species, in 2007 and 2008. METHODS:
      Human tularemia cases are mandatorily notifiable in France since 2003. In hares,
      surveillance relies on volunteer hunter associations in all districts of the
      country. Data from mandatory reports and volunteer surveillance in 2007/2008 were
      analyzed and compared with previous results. RESULTS: In 2007/2008, 144 cases
      were reported in humans and 117 cases in hares. This was a 100% increase compared
      to previous years. Human cases differed from those of previous years only by the
      frequency of contact with breeding animals. Human cases without any documented
      risk exposure were also more frequent. CONCLUSION: An increase of tularemia cases
      occurred in 2007/2008 in both species. Complementary studies are needed to
      identify the species reservoir in France to understand the causes of this peak of
      cases.

PMID- 20044228
TI  - Contribution of endoscopic ultrasound-guided fine-needle aspiration in the workup
      of mediastinal lymph nodes.
AB  - BACKGROUND AND AIM: The aim of this retrospective study was to assess endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA), a minimally invasive
      technique, to determine its diagnostic accuracy and morbidity in the etiological
      diagnoses of mediastinal lymph nodes. METHODS: A total of 84 patients underwent
      EUS-FNA biopsy of the mediastinal lymph nodes, and were classified as either
      malignant disease, inflammatory disease or incidental diagnosis, according to the
      suspected clinical condition. To evaluate the diagnostic accuracy of EUS-FNA in
      each group, a comparison of the cytological results obtained with 19- and 22
      gauge needles was performed. RESULTS: All 84 procedures were carried out between
      January 2004 and June 2008. Six patients were excluded because of non
      contributory results. On analyzing the results of EUS-FNA in the malignant group
      (n=41), the sensitivity, specificity, positive predictive value (PPV) and
      negative predictive value (NPV) were 93, 100, 100 and 85%, respectively. In the
      inflammatory (n=20) and incidental diagnosis (n=17) groups, the sensitivity,
      specificity, PPV and NPV were 85, 100, 100 and 75%, and 80, 100, 100 and 77%,
      respectively. There was no significant difference between the FNA results with
      the 19-gauge (20/78 patients) versus 22-gauge (58/78 patients) needles (P=0.55).
      Also, no complications were reported either during the procedure or after the 6
      month follow-up. CONCLUSION: EUS-FNA is a safe and accurate diagnostic procedure
      for the study of mediastinal lymph nodes not only for malignancy, but also for
      inflammatory diseases and incidental diagnoses. In addition, there is no
      difference in diagnostic accuracy whether FNA is carried out with a 19-gauge or
      22-gauge needle.

PMID- 20044229
TI  - Influence of physical factors on the accuracy of calibration models for NIR
      spectroscopy.
AB  - The quality of pharmaceutical drugs is strongly influenced by a number of
      physical and chemical factors that require careful control during the production
      process in order to ensure that the end-product will meet the specifications.
      Near infrared spectroscopy has proved effective for monitoring changes in such
      factors and is currently the most widely used technique for controlling drug
      manufacturing processes. In this work, the authors determined an active
      pharmaceutical ingredient (API) throughout its production process. The influence
      of particle size, galenic form, compaction pressure and coating thickness on NIR
      spectra was evaluated with a view to developing effective methodologies for
      constructing simple, accurate calibration methods affording API quantization at
      different stages of a drug production process. All calibration models were
      constructed from data for laboratory samples alone and NIR calibration models for
      determining the API determination by using product weights as reference values.
      The proposed models were validated by application to samples obtained at three
      stages of a drug manufacturing process and comparison of the predicted values
      with HPLC reference values. The RSEP values thus obtained never exceeded 1.5%.

PMID- 20044230
TI  - The effect of conflicting medication information and physician support on
      medication adherence for chronically ill patients.
AB  - OBJECTIVE: This article explores the effect of conflicting information, defined
      as contradictory information about medication topics from different sources, on
      medication adherence in a sample of chronically ill patients. We specifically
      investigate whether conflicting information and physician support directly affect
      medication adherence or whether the effect is mediated by adherence self-efficacy
      and outcome expectations for medications. METHODS: Vasculitis patients (n = 228)
      completed two on-line questionnaires which contained measures of conflicting
      information, adherence self-efficacy, outcome expectations, physician support,
      and medication adherence. We conducted a mediation analysis using a bootstrapping
      approach to generate point estimates and 95% confidence intervals to test the
      significance of each mediated effect. RESULTS: A majority of patients (51.3%)
      received conflicting medication information. Conflicting information had a direct
      negative effect on medication adherence, which was not mediated by self-efficacy
      or outcome expectations. Alternatively, self-efficacy mediated the positive
      effect of physician support on medication adherence. CONCLUSION: Patients who
      encounter conflicting medication information are less adherent to their
      medications. The presence of a supportive physician may counteract the negative
      effect of conflicting medication information. PRACTICE IMPLICATIONS: Physicians
      should initiate conversations about conflicting medication information with their
      patients. Consensus-based guidelines that address medication discrepancies may
      also reduce the availability of conflicting information.

PMID- 20044231
TI  - Evaluating the implementation of peer counseling in a church-based dietary
      intervention for African Americans.
AB  - OBJECTIVE: Body & Soul, an evidence-based nutrition program for African Americans
      churches, is currently being disseminated nationally and free of charge by the
      National Cancer Institute. For dissemination feasibility, the peer counseling
      training is done via DVD rather than by live trainers. We describe implementation
      and process evaluation of the peer counseling component under real world
      conditions. METHODS: The study sample included 11 churches (6 early intervention,
      5 delayed intervention) in 6 states. Data sources included training observations,
      post-training debriefing sessions, coordinator interviews, and church participant
      surveys. Survey data analysis examined associations between exposure to peer
      counseling and change in dietary intake. Qualitative data were analyzed using the
      constant comparative method. RESULTS: Eight of 11 churches initiated the peer
      counseling program. Recall of talking with a peer counselor was associated with
      significantly (p<.02) greater fruit and vegetable intake. Data indicate sub
      optimal program execution after peer counselor training. CONCLUSION: Inconsistent
      implementation of the peer counseling intervention is likely to dilute program
      effectiveness in changing nutrition behaviors. PRACTICE IMPLICATIONS:
      Disseminating evidence-based programs may require added resources, training,
      quality control, and technical assistance for improving program uptake. Similar
      to earlier research phases, systematic efforts at the dissemination phase are
      needed for program success.

PMID- 20044232
TI  - Development and validation of a low-literacy Chronic Obstructive Pulmonary
      Disease knowledge Questionnaire (COPD-Q).
AB  - OBJECTIVE: The objective of this study was to develop a content valid,
      understandable, readable, and reliable Chronic Obstructive Pulmonary Disease
      knowledge Questionnaire (COPD-Q). METHODS: Twenty-one questions were generated as
      potential items to include in the COPD-Q. Twenty-two content experts provided
      both qualitative and quantitative assessments of two COPD-Q drafts. Ten patient
      volunteers completed a field test to assess clarity of individual COPD-Q items.
      An additional 24 patient volunteers completed a pilot test to determine internal
      consistency and test-retest reliability of the COPD-Q. The Flesch Reading Ease
      (FRE) was used to assess reading grade level of the COPD-Q. RESULTS: Thirteen
      items were rated as "essential" (content validity ratio= p <0.05) by content
      experts and composed the final COPD-Q. Internal consistency, using Cronbach's
      alpha, was 0.72. Test-retest reliability, using intraclass correlation
      coefficient, was 0.90. The FRE score of the COPD-Q was 74.7 (equivalent to a 5th
      grade reading level). CONCLUSION: The COPD-Q is a valid, readable and reliable
      knowledge assessment instrument for assessing COPD knowledge in patients who may
      have low health literacy skills. PRACTICE IMPLICATIONS: Health care providers can
      use the COPD-Q to tailor counseling efforts according to individual patient
      needs, and to assess the effectiveness of their educational interventions.

PMID- 20044233
TI  - Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R
      DHAOx) produces a strong long-term antitumor effect in previously treated
      patients with follicular non-Hodgkin's lymphoma.
AB  - BACKGROUND: We explored the addition of rituximab to high-dose cytarabine (ara
      C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed
      patients with CD20-positive follicular non-Hodgkin's lymphoma. METHODS: Twenty
      two patients were included; they were treated previously with one to five
      chemotherapy regimens, including 13 patients who had also received rituximab. R
      DHAOx consisted of rituximab, 375mg/m(2), day 1; dexamethasone, 40mg/d, days one
      to four; L-OHP, 130mg/m(2), day 1; and ara-C, 2000mg/m(2) every 12 h, day 2.
      Courses were repeated every 21 days for eight courses. RESULTS: Twenty-one
      patients (95%) achieved a complete response and one had a partial response.
      Responses were obtained in patients with and without resistance to prior
      treatment, either alone or combined with rituximab. The median follow-up time was
      58.3 months (range, 8.7-92.6 months). Progression-free survival reached a plateau
      at 84% at 38.2 months. Only two of the 21 complete responders have relapsed.
      Tumor molecular markers disappeared in all 10 complete responders whose markers
      were found before treatment. Peripheral neuropathy related to the cumulative dose
      of L-OHP, and myelosuppression were the most prominent toxic effects.
      CONCLUSIONS: R-DHAOx is highly active for salvage treatment of patients with
      follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.

PMID- 20044234
TI  - Effect of telmisartan on QT interval variability and autonomic control in
      hypertensive patients with left ventricular hypertrophy.
AB  - OBJECTIVES: The aim of the study was to examine the effect of the
      antihypertensive AT1 receptors antagonist telmisartan on cardiovascular autonomic
      function and QT dispersion in hypertensive patients with LVH. METHODS: Twenty
      five patients (18 males and seven women, mean age 49.8+/-5.2 years) with mild
      essential arterial hypertension and LVH were compared with 25 age-matched healthy
      controls. All the participants underwent a complete clinical examination,
      including electrocardiogram for QT interval measurements and 24h ambulatory ECG
      monitoring for measurement of heart rate variability. The ECG, 24h ambulatory
      ECG, and echocardiogram were repeated after eight weeks of treatment. RESULTS: At
      baseline, hypertensive patients showed QT dispersion (p<0.001) and QTc dispersion
      (p<0.001) significantly higher than control subjects. An eight-week telmisartan
      treatment significantly reduced blood pressure (p<0.0001), without significant
      change in left ventricular mass. Telmisartan-based treatment induced an increased
      vagal activity without significant change of sympathetic activity and a reduction
      of QT dispersion (p<0.001) and QTc dispersion (p<0.001). CONCLUSIONS: These data
      suggest that therapy with telmisartan significantly improves the sympathovagal
      balance increasing parasympathetic activity, and cardiac electrical stability
      reducing the heterogeneity of ventricular repolarization in hypertensive
      subjects. These effects could contribute to reduce arrhythmias as well as sudden
      cardiac death in at-risk hypertensive patients.

PMID- 20044235
TI  - An improved 3D shape context based non-rigid registration method and its
      application to small animal skeletons registration.
AB  - 3D shape context is a method to define matching points between similar shapes. It
      can be used as a pre-processing step in a non-rigid registration. The main
      limitation of the method is point mismatching, which includes long geodesic
      distance mismatch causing wrong topological structure, and neighbors crossing
      mismatch between two adjacent points. In this paper, we propose a topological
      structure verification method to correct the long geodesic distance mismatch and
      a correspondence field smoothing method to correct the neighbors crossing
      mismatch. A robust 3D shape context model is generated and further combined with
      thin-plate spline model for non-rigid registration. The method was tested on
      phantoms and applied to rat hind limb and mouse hind limb skeletons registration
      from micro-CT images. Errors between the registered surfaces were reduced by
      using the proposed method. The robustness of the method is demonstrated.

PMID- 20044236
TI  - Automated classification of multi-spectral MR images using Linear Discriminant
      Analysis.
AB  - Magnetic resonance imaging (MRI) is a valuable instrument in medical science
      owing to its capabilities in soft tissue characterization and 3D visualization. A
      potential application of MRI in clinical practice is brain parenchyma
      classification. This work proposes a novel approach called "Unsupervised Linear
      Discriminant Analysis (ULDA)" to classify and segment the three major tissues,
      i.e. gray matter (GM), white matter (WM) and cerebral spinal fluid (CSF), from a
      multi-spectral MR image of the human brain. The ULDA comprises two processes,
      namely Target Generation Process (TGP) and Linear Discriminant Analysis (LDA)
      classification. TGP is a fuzzy-set process that generates a set of potential
      targets from unknown information, and applies these targets to train the optimal
      division boundary by LDA, such that three tissues GM, WM and CSF are separated.
      Finally, two sets of images, namely computer-generated phantom images and real MR
      images are used in the experiments to evaluate the effectiveness of ULDA.
      Experiment results reveal that UDLA segments a multi-spectral MR image much more
      effectively than either FMRIB's Automated Segmentation Tool (FAST) or Fuzzy C
      means (FC).

PMID- 20044237
TI  - Nonparametric joint shape learning for customized shape modeling.
AB  - We present a shape optimization approach to compute patient-specific models in
      customized prototyping applications. We design a coupled shape prior to model the
      transformation between a related pair of surfaces, using a nonparametric joint
      probability density estimation. The coupled shape prior forces with the help of
      application-specific data forces and smoothness forces drive a surface
      deformation towards a desired output surface. We demonstrate the usefulness of
      the method for generating customized shape models in applications of hearing aid
      design and pre-operative to intra-operative anatomic surface estimation.

PMID- 20044238
TI  - A comparison between 2D and 3D cephalometry on CBCT scans of human skulls.
AB  - The purpose of this study was to evaluate whether measurements on conventional
      cephalometric radiographs are comparable with 3D measurements on 3D models of
      human skulls, derived from cone beam CT (CBCT) data. A CBCT scan and a
      conventional cephalometric radiograph were made of 40 dry skulls. Standard
      cephalometric software was used to identify landmarks on both the 2D images and
      the 3D models. The same operator identified 17 landmarks on the cephalometric
      radiographs and on the 3D models. All images and 3D models were traced five times
      with a time-interval of 1 week and the mean value of repeated measurements was
      used for further statistical analysis. Distances and angles were calculated.
      Intra-observer reliability was good for all measurements. The reproducibility of
      the measurements on the conventional cephalometric radiographs was higher
      compared with the reproducibility of measurements on the 3D models. For a few
      measurements a clinically relevant difference between measurements on
      conventional cephalometric radiographs and 3D models was found. Measurements on
      conventional cephalometric radiographs can differ significantly from measurements
      on 3D models of the same skull. The authors recommend that 3D tracings for
      longitudinal research are not used in cases were there are only 2D records from
      the past.

PMID- 20044239
TI  - Children with new-onset epilepsy exhibit diffusion abnormalities in cerebral
      white matter in the absence of volumetric differences.
AB  - The purpose of this investigation was to examine the diffusion properties of
      cerebral white matter in children with recent onset epilepsy (n=19) compared to
      healthy controls (n=11). Subjects underwent DTI with quantification of mean
      diffusion (MD), fractional anisotropy (FA), axial diffusivity (D(ax)) and radial
      diffusivity (D(rad)) for regions of interest including anterior and posterior
      corpus callosum, fornix, cingulum, and internal and external capsules.
      Quantitative volumetrics were also performed for the corpus callosum and its
      subregions (anterior, midbody and posterior) and total lobar white and gray
      matter for the frontal, parietal, temporal and occipital lobes. The results
      demonstrated no group differences in total lobar gray or white matter volumes or
      volume of the corpus callosum and its subregions, but did show reduced FA and
      increased D(rad) in the posterior corpus callosum and cingulum. These results
      provide the earliest indication of microstructural abnormality in cerebral white
      matter among children with idiopathic epilepsies. This abnormality occurs in the
      context of normal volumetrics and suggests disruption in myelination processes.

PMID- 20044240
TI  - Comparison of hippocampal Deep Brain Stimulation with high (130Hz) and low
      frequency (5Hz) on afterdischarges in kindled rats.
AB  - Hippocampal Deep Brain Stimulation (DBS) is proposed as an experimental treatment
      for refractory epilepsy, but the optimal stimulation parameters are undetermined.
      High frequency hippocampal DBS at 130Hz is effective in both animals and patients
      with epilepsy. Low frequency stimulation (approximately 5Hz) is assumed to have
      anti-epileptic properties but the efficacy is highly debated. This animal study
      compares the effects of both stimulation modalities in kindled rats. Sprague
      Dawley rats (n=20) were fully kindled according to the Alternate Day Rapid
      Kindling-protocol. After a baseline kindling period, rats were divided into a
      high frequency group (HFS, 130Hz, n=11) and a low frequency group (LFS, 5Hz,
      n=9), both receiving 10 days of continuous DBS. During and after DBS, the seizure
      susceptibility of all rats was tested and the characteristics of the
      afterdischarges (ADs) were compared between both treatments. During HFS, AD
      threshold was higher (p<0.05) and at the stimulated site, AD latency was longer
      (p<0.01) than during baseline period. During LFS, a similar but smaller change
      was observed, but did not reach significance. The duration of the AD was not
      affected by either HFS or LFS. After termination of HFS, the effects on AD
      latency and AD threshold recovered to baseline. In conclusion, high frequency
      stimulation at 130Hz is more effective than LFS (5Hz) in affecting excitability
      in epileptic rats. This is reflected in a higher AD threshold and longer AD
      latency during application of stimulation.

PMID- 20044241
TI  - Quantitative MRI predicts status epilepticus-induced hippocampal injury in the
      lithium-pilocarpine rat model.
AB  - Convulsive status epilepticus (SE) is a common medical neurological emergency and
      is associated with hippocampal injury and the subsequent development of epilepsy.
      However, pathophysiological mechanisms that underlie injury remain unclear, and a
      clinically useful prognostic biomarker of at-risk patients remains elusive. We
      hypothesised that non-invasive quantitative multi-parametric MRI characterisation
      of the early time course in the lithium-pilocarpine rat model would provide
      insight into pathophysiological processes, and may help to develop a non-invasive
      prognostic marker of hippocampal injury. T(1), T(2), apparent diffusion
      coefficient (ADC), and cerebral blood flow (CBF) were measured before and after
      SE on days 0, 1, 2, 3, 7, 14 and 21. Hippocampal volume measurements were used to
      assess final structural outcome. MRI changes were found in the parietal cortex,
      hippocampus, piriform cortex, and thalamus. Each of the regions displayed time
      dependent changes, and returned to baseline levels by Day 7. Hippocampal
      measurements peaked on Day 2, and further analysis revealed that the magnitude of
      these peak changes was predictive of the hippocampal volumes on Day 21. This time
      course is consistent with cell death and an inflammatory process. The maximal
      changes provide a potential clinically useful prognostic marker of final
      hippocampal volume.

PMID- 20044242
TI  - Bronchodilatory effects of aclidinium bromide, a long-acting muscarinic
      antagonist, in COPD patients.
AB  - BACKGROUND: Aclidinium bromide is a novel, long-acting, inhaled muscarinic
      antagonist bronchodilator currently in Phase III clinical development for the
      treatment of chronic obstructive pulmonary disease (COPD). This study evaluated
      the pharmacodynamics, pharmacokinetics, safety and tolerability of ascending
      doses of aclidinium bromide in patients with COPD. METHODS: This double-blind,
      randomised, placebo-controlled, crossover study was conducted in patients with
      moderate to severe COPD (forced expiratory volume in 1s [FEV(1)] <65% predicted).
      Patients were randomly assigned to one of four treatment sequences of aclidinium
      bromide 100, 300, 900microg and placebo with a washout period between doses. The
      primary outcome was area under the FEV(1) curve over the 0-24h time interval.
      RESULTS: Seventeen patients with COPD were studied. Mean FEV(1) over 24h was
      1.583L for placebo, and 1.727L, 1.793L and 1.815L for aclidinium bromide 100, 300
      and 900microg, respectively (p<0.001 vs. placebo, all doses). Significant changes
      from baseline in FEV(1) were detected 15min post-dose for aclidinium bromide 300
      and 900microg, with a peak effect 2h post-dose (all doses). Aclidinium bromide
      was undetected in plasma. The majority of adverse events was unrelated to study
      medication and did not result in discontinuation. CONCLUSION: Aclidinium bromide
      100-900microg produced sustained bronchodilation over 24h in patients with COPD.

PMID- 20044243
TI  - Autophagy regulation by p53.
AB  - Autophagy is an evolutionarily conserved catabolic pathway that is involved in
      numerous physiological processes and in multiple pathological conditions
      including cancer. Autophagy is regulated by an intricate network of signaling
      cascades that have not yet been entirely disentangled. Accumulating evidence
      indicates that p53, the best-characterized human tumor suppressor protein, can
      modulate autophagy in a dual fashion, depending on its subcellular localization.
      On the one hand, p53 functions as a nuclear transcription factor and
      transactivates proapoptotic, cell cycle-arresting and proautophagic genes. On the
      other hand, cytoplasmic p53 can operate at mitochondria to promote cell death and
      can repress autophagy via poorly characterized mechanisms. This review focuses on
      the recently discovered function of p53 as a master regulator of autophagy.

PMID- 20044244
TI  - Biosensor based on hydrogel optical waveguide spectroscopy.
AB  - A novel label-free biosensor based on the measurement of binding-induced
      refractive index changes by hydrogel optical waveguide spectroscopy (HOWS) is
      reported. This biosensor is implemented by using a surface plasmon resonance
      (SPR) optical setup in which a carboxylated poly(N-isoproprylacrylamide)
      (PNIPAAm) hydrogel film is attached on a metallic surface and modified by protein
      catcher molecules through amine coupling chemistry. The swollen hydrogel with
      micrometer thickness serves both as a binding matrix and optical waveguide. We
      show that compared to regular SPR biosensor with thiol self-assembled monolayer
      (SAM), HOWS provides an order of magnitude improved resolution in the refractive
      index measurements and enlarged binding capacity owing to its low damping and
      large swelling ratio, respectively. A model immunoassay experiment revealed that
      HOWS allowed detection of IgG molecules (molecular weight 150 kDa) with a 10 pM
      limit of detection that was 5-fold lower than that achieved for SPR with thiol
      SAM. For the high capacity hydrogel matrix, the affinity binding was mass
      transport limited. Therefore, we envisage that HOWS will provide further improved
      detection limit for low molecular weight analytes or for assays employing lower
      affinity catcher molecules.

PMID- 20044245
TI  - Detection of G protein-coupled receptor-mediated cellular response involved in
      cytoskeletal rearrangement using surface plasmon resonance.
AB  - G protein-coupled receptors (GPCRs) form a superfamily of cell surface receptors
      that play fundamental roles in physiology and pathophysiology. Although GPCRs
      have been the most successful targets for drug discovery, there still remain many
      orphan GPCRs, which provides opportunities for development of novel drugs. Here,
      we introduce a new method for evaluation of GPCR activation utilizing a surface
      plasmon resonance (SPR) sensor. Cells expressing GPCRs were cultured directly on
      an SPR sensor chip and stimulated with GPCR ligands, resulting in SPR responses
      that were dependent on the type of G alpha subunits coupling with receptors.
      Namely G(i)- and/or G(12/13)-coupled receptors evoked SPR responses but G(s)- or
      G(q)-coupled ones did not. Analyses on the intracellular signal pathways revealed
      that small G protein Rho/Rac-mediated actin rearrangement plays an important role
      in the signal transduction pathways leading to the SPR responses. An SPR response
      was also evoked by insulin-like growth factor-1, which stimulates Rac-dependent
      stress fiber formation via its receptor-tyrosine kinase. Thus, this method
      provides a unique opportunity for real-time monitoring of cellular responses
      involved in cytoskeletal rearrangements, and may be useful in ligand/drug
      discovery for certain types of receptor, such as G(i)- and G(12/13)-coupled
      receptors.

PMID- 20044246
TI  - The European Network for the Study of Adrenal Tumors staging system is
      prognostically superior to the international union against cancer-staging system:
      a North American validation.
AB  - BACKGROUND: A reclassification of the International Union Against Cancer (UICC)
      staging system for adrenocortical carcinoma (ACC) patients has recently been
      proposed by the European Network for the Study of Adrenal Tumors (ENSAT) to
      better discriminate between cancer-specific mortality (CSM) risk strata. We
      formally tested the validity of the modified staging system in a large North
      American population-based cohort. METHODS: Kaplan-Meier survival curves depicted
      CSM rates in the overall population and after stratification according to the
      2004 UICC or the 2008 ENSAT-staging system. Cox regression models addressing CSM
      tested the prognostic value of respectively the UICC or the ENSAT-staging system.
      Harrell's concordance index quantified the accuracy of the standard versus the
      modified staging system. RESULTS: In the overall population (n=573), the CSM-free
      survival rates at 1, 3, and 5 years were, respectively, 62.9%, 47.0%, and 38.1%.
      No statistically significant differences in survival were recorded between 2004
      UICC stages II and III patients (p=0.1). Conversely, a statistically significant
      difference was observed between 2008 ENSAT stage II and stage III patients
      (p<0.001). The 2008 ENSAT-staging system showed higher accuracy (83.0%) in
      predicting 3-year CSM rates, relative to the 2004 UICC-staging system (79.5%)
      (p<0.001). CONCLUSION: Our study corroborates the superior accuracy of the ENSAT
      staging system for ACC relative to the 2004 UICC-staging system. In consequence,
      the 2008 ENSAT-staging system may warrant consideration in the next update of
      staging manuals.

PMID- 20044247
TI  - The stromal part of adenocarcinomas of the oesophagus: does it conceal targets
      for therapy?
AB  - OBJECTIVE: To evaluate the prognostic value of the tumour stroma ratio (TSR) in
      resected adenocarcinoma of the oesophagus. BACKGROUND: In the literature, a
      refinement of oesophageal cancer staging has been proposed. Recently, TSR has
      been identified as a histological characteristic of the tumour itself that proved
      to be a strong predictor for survival in colorectal cancer. METHODS: In our
      cancer registry database, we identified 93 consecutive patients who underwent
      resection for oesophageal adenocarcinoma between 1990 and 2004 in two hospitals
      in our region. Using a predefined histopathological protocol, TSR was determined
      on the original haematoxylin-eosin (H&E) tissue sections of oesophagectomy
      specimens by two independent investigators. RESULTS: With a cut-off value of 50%
      tumour/stroma, patients were classified as TSR high (n=60) or TSR low (n=33).
      There were no significant differences in patient, tumour and treatment
      characteristics between the two groups, except for M status (M1a) and radicality
      of resection. The (disease-free) survival in the TSR high group was significantly
      better than in the TSR low group. By multivariate analysis, TSR was identified as
      a highly significant prognostic factor for overall survival (HR 2.0; P=0.010),
      independent of depth of tumour invasion, nodal status, lymph node ratio,
      extracapsular involvement, TNM stage, histological grade and radicality of
      resection. CONCLUSION: TSR is a new and practicable prognostic tumour
      characteristic for oesophageal adenocarcinoma that can discriminate patients with
      a poor outcome from those with a better outcome.

PMID- 20044248
TI  - Predicting the adsorption of second generation biofuels by polymeric resins with
      applications for in situ product recovery (ISPR).
AB  - The application of hydrophobic polymeric resins as solid-phase adsorbent
      materials for the recovery and purification of prospective second generation
      biofuel compounds, including ethanol, iso-propanol, n-propanol, iso-butanol, n
      butanol, 2-methyl-1-butanol, 3-methyl-1-butanol, and n-pentanol, has been
      investigated. A simple, yet robust correlation has been proposed to model the
      relative equilibrium partitioning behavior of a series of branched and n-alcohols
      as a function of their relative hydrophobicity, and has been applied to
      ultimately predict their adsorption potential. The proposed model adequately
      predicts the adsorption behavior of the entire series of alcohols studied, as
      well as with six different adsorbent phases composed of three different polymer
      matrices. Those resins with a non-polar monomeric structure and high specific
      surface area provided the highest overall adsorption of each of the studied
      compounds. Meanwhile, longer chain alcohols were subject to greater adsorption
      due to their increasingly hydrophobic nature. Among the tested series of
      alcohols, five-carbon isomers displayed the greatest potential for economical
      recovery in future, multiphase bioprocess designs. The present study provides the
      first demonstration of the ability of hydrophobic polymer resins to serve as
      effective in situ product recovery (ISPR) devices for the production of second
      generation biofuels.

PMID- 20044249
TI  - Growth of Pseudomonas sp. TX1 on a wide range of octylphenol polyethoxylate
      concentrations and the formation of dicarboxylated metabolites.
AB  - Pseudomonas sp. TX1, is able to use octylphenol polyethoxylates (OPEO(n), or
      Triton X-100; average n = 9.5) as a sole carbon source. It can grow on 0.05-20%
      of OPEO(n) with a specific growth rate of 0.34-0.44 h(-1). High-performance
      liquid chromatography-mass spectrometer analysis of OPEO(n) degraded metabolites
      revealed that strain TX1 was able to shorten the ethoxylate chain and produce
      octylphenol (OP). Furthermore, formation of the short carboxylate metabolites,
      such as carboxyoctylphenol polyethoxylates (COPEO(n), n = 2, 3) and
      carboxyoctylphenol polyethoxycarboxylates (COPEC(n), n = 2, 3) began at the log
      stage, while octylphenol polyethoxycarboxylates (OPEC(n), n = 1-3) was formed at
      the stationary phase. All the short-ethoxylated metabolites, OPEO(n), OPEC(n),
      COPEO(n), and COPEC(n), accumulated when the cells were in the stationary phase.
      This study is the first to demonstrate the formation of COPEO(n) and COPEC(n)
      from OPEO(n) by an aerobic bacterium.

PMID- 20044250
TI  - Consolidated bioprocessing of sugarcane bagasse and chicken manure to ammonium
      carboxylates by a mixed culture of marine microorganisms.
AB  - The MixAlco process, an example of consolidated bioprocessing (CBP), was utilized
      for anaerobic fermentation of 80% lime-treated sugarcane bagasse/20% chicken
      manure at 55 degrees Celsius by a mixed culture of marine microorganisms.
      NH(4)HCO(3) was recommended by this study to replace CaCO(3) buffer to neutralize
      the produced carboxylic acids. The resulting ammonium carboxylates can be
      converted to gasoline or mixed alcohol fuels by downstream processing. Four-stage
      countercurrent fermentations at various volatile solids loading rates (VSLR) and
      liquid residence times (LRT) showed the highest acid productivity (1.27 g/(L x
      day)) and highest conversion (76%) occurred at a total acid concentration of 24.4
      and 31.3g/L, respectively. The Continuum Particle Distribution Model (CPDM)
      predicted the experimental total acid concentrations and conversions within 9.05%
      and 14.39%, respectively. The CPDM "map" indicates that both high acid
      concentrations (>50 g/L) and high conversions (>72%) are possible with 300 g
      substrate/(L liquid) concentration, 30 days liquid residence time, 5.4 g/(L x
      day) solid loading rate, and NH(4)HCO(3) buffer. The present study suggests that
      mixed culture biotechnology in the MixAlco process provides an alternative
      "carboxylate platform" for biomass conversion.

PMID- 20044251
TI  - Energy recovery from secondary pulp/paper-mill sludge and sewage sludge with
      supercritical water treatment.
AB  - Secondary pulp/paper-mill sludge (SPP) and sewage sludges (primary, secondary,
      and digested sewage sludges) were treated in supercritical water at temperatures
      ranging between 400 degrees Celsius and 550 degrees Celsius over 20-120 min for
      energy recovery. Low temperature and short reaction time favored the formation of
      heavy oil (HO) products, which were mainly composed of a variety of phenol and
      phenolic compounds, as well as some nitrogen-containing compounds, long-chain
      alkenes and alcohols, etc., with high gross calorific values (>36 MJ/kg). By
      contrast, the formation of synthetic gases, a mixture of hydrogen, carbon
      monoxide, carbon dioxide, methane, and other light hydrocarbons, were not
      significantly affected by reaction time but greatly enhanced with increasing
      temperature. The highest gas yield was obtained at 550 degrees Celsius, where
      37.7 wt.% of the SPP (on dry basis) was converted into gases, with hydrogen
      yields as high as 14.5 mol H(2)/kg SPP (on a dry basis). In comparison to sewage
      sludges, SPP exhibited a greater capability for the production of HO and gases
      owing to its higher contents of volatiles and alkali metals, indicating a
      prospective utilization potential for SPP as a source of bio-energy.

PMID- 20044252
TI  - Laccase catalyzed covalent coupling of fluorophenols increases lignocellulose
      surface hydrophobicity.
AB  - This work presents for the first time the mechanistic evidence of a laccase
      catalyzed method of covalently grafting hydrophobicity enhancing fluorophenols
      onto Fagus sylvatica veneers. Coupling of fluorophenols onto complex lignin model
      compounds guaiacylglycerol beta-guaiacyl ether and syringylglycerol beta-guaiacyl
      ether was demonstrated by LC-MS and NMR. Laccase-mediated coupling increased
      binding of 4-[4-(trifluoromethyl)phenoxy]phenol (4,4-F3MPP) and 4
      (trifluoromethoxy)phenol (4-F3MP) to veneers by 77.1% and 39.2%, respectively.
      XPS studies showed that laccase-catalyzed grafting of fluorophenols resulted in a
      fluorine content of 6.39% for 4,4-F3MPP, 3.01% for 4-F3MP and 0.26% for 4-fluoro
      2-methylphenol (4,2-FMP). Grafting of the fluorophenols 4,2-FMP, 4-F3MP and 4,4
      F3MPP led to a 9.6%, 28.6% and 65.5% increase in hydrophobicity, respectively,
      when compared to treatments with the respective fluorophenols in the absence of
      laccase, in good agreement with XPS data.

PMID- 20044253
TI  - Comparison of arsenic accumulation in 18 fern species and four Pteris vittata
      accessions.
AB  - This study evaluated the ability and mechanisms of 19 Pteris and non-Pteris
      species to accumulate arsenic (As) in a hydroponic system spiked with 300 microM
      As. The study included four Pteris vittata accessions (China, India, Poland, and
      the United Kingdom), P. biaurita and 17 non-Pteris species. Among the accessions,
      P. vittata from China and UK were the most and the least efficient in terms of As
      accumulation. The non-Pteris species Chielanthes sinuta, Adiantum raddianum,
      Polystichum acrostichoides, Actiniopteris radiata, Pellaea rotundifolia, and
      Nephrolepis cordifolia concentrated As as effectively as the least efficient P.
      vittata ascension. As (III) in the fronds of P. vittata accessions ranged from
      59% to 89% and for non-Pteris species it ranged from 47% to 65%. Maximum As
      accumulation coincided with highest percentage of As (III) in the fronds. The
      phosphorus (P) uptake of P. vittata accessions was 12-15 and 6-12 times greater
      than the As-uptake in the roots and fronds, respectively. In contrast, the P
      uptake of non-Pteris species ranged from 9 to 151 and from 4 to 162 times the As
      uptake, in the roots and fronds, respectively. Arsenic accumulation occurs at the
      expense of root and frond P-uptake. Root P-reduction is lower than frond and the
      P:As in the plant acquisition part (roots) is 1-3 times greater than that in
      accumulation part (fronds). A. radiata, C. sinuta, and P. acrostichoides were
      identified as potential As accumulators.

PMID- 20044254
TI  - Side chain SAR of bicyclic beta-lactamase inhibitors (BLIs). 1. Discovery of a
      class C BLI for combination with imipinem.
AB  - Bridged monobactam beta-lactamase inhibitors were prepared and evaluated as
      potential partners for combination with imipenem to overcome class C beta
      lactamase mediated resistance. The (S)-azepine analog 2 was found to be effective
      in both in vitro and in vivo assays and was selected for preclinical development.

PMID- 20044255
TI  - Inhibition of IKK-beta: a new development in the mechanism of the anti-obesity
      effects of PTP1B inhibitors SA18 and SA32.
AB  - In a previous study, protein tyrosine phosphatase 1B (PTP1B) inhibitors, SA18 and
      SA32, exhibited anti-obesity effects in a mouse model by suppressing weight gain
      and improving blood parameters, including free fatty acid (FFA) levels. In a
      separate study, depletion of the PTP1B gene in mice suppressed weight gain
      without significant change in FFA levels. The discrepancy in FFA concentrations
      between the two studies suggested that the in vivo target of the SA compounds
      might not be limited to PTP1B. In this study, SA18 and SA32 were found to be
      potent inhibitors of IkappaB Kinase-beta (IKK-beta). In vivo relevance of the
      inhibitory activity was evaluated in differentiated adipocytes. Inhibition of IKK
      beta, in addition to inhibition of PTP1B, in mice treated with the SA compounds,
      could be a possible mechanism of the compound's biological response including the
      resistance to diet-induced weight gain and improvement in blood parameters. As
      potent and cell-permeable IKK-beta inhibitors, SA18 and SA32 could also be
      valuable in biological experiments.

PMID- 20044256
TI  - Are vital signs valid indicators for the assessment of pain in postoperative
      cardiac surgery ICU adults?
AB  - The aim of this study was to examine the discriminant and criterion validity of
      vital signs (mean arterial pressure [MAP], heart rate [HR], respiratory rate
      [HR], transcutaneous oxygen saturation [SpO(2)], and end-tidal CO(2)) for pain
      assessment in postoperative cardiac surgery ICU adults. A repeated-measure within
      subject design was used. A convenience sample of 105 patients from a cardiology
      health center in Canada participated. Patients were observed during three testing
      periods: (1) unconscious and mechanically ventilated, (2) conscious and
      mechanically ventilated and (3) after extubation. For each of these testing
      periods, vital signs were assessed using the ICU monitoring at rest, during a
      nociceptice procedure and 20 min post-procedure. Conscious patients' self-reports
      of pain were obtained. Discriminant validity was supported with significant
      changes in most vital signs during the nociceptive procedure. Some of the vital
      signs (HR, RR, and SpO(2)) were associated with the patients' self-reports of
      pain but were dependent on the patients' status (mechanically ventilated or not).
      Findings regarding the use of vital signs for pain assessment are not consistent
      and should be considered with caution. As recommended by experts, vital signs
      should only be used as a cue when behavioural indicators are no longer available
      in mechanically ventilated or unconscious patients.

PMID- 20044257
TI  - Plantar pressure measurements using an in-shoe system and a pressure platform: a
      comparison.
AB  - This study compared three different foot-pressure measurement methods to
      investigate whether these measurement methods could or should be used
      interchangeably. In-shoe pressure measurements using F-Scan system, shod and
      unshod pressure measurements using the MatScan system were taken for each of the
      21 healthy subjects while performing walking trials using a two-step gait
      initiation protocol. Each foot was separated in three regions: forefoot (40%),
      midfoot (30%) and rearfoot (30%) for further analysis. The parameters researched
      include average peak pressure, average peak force, timing and centre of pressure
      displacement. The in-shoe condition produced the highest values for the average
      peak force. However, the shod condition showed a trend for the highest average
      peak pressure. The F-Scan system consistently demonstrated slower timing values
      for all parameters, except one. Centre of pressure anterior/posterior trajectory
      was considerably shorter for the in-shoe gait condition. Consequently, the data
      cannot be extrapolated from one collection method to another. It is therefore
      recommended that a standardised collection method is utilised when pressure
      analysis is undertaken and that they are not used interchangeably.

PMID- 20044258
TI  - Risedronate decreases bone resorption and improves low back pain in
      postmenopausal osteoporosis patients without vertebral fractures.
AB  - Elderly postmenopausal women who have osteoporosis sometimes experience low back
      pain, however, the relationship between low back pain and osteoporosis in the
      absence of vertebral fractures remains unclear. We examined the relationship
      between bone mineral density (BMD), bone resorption and low back pain in elderly
      female patients who did not have osteoporotic vertebral fractures. The average
      BMD was 0.675 g/cm(2) when assessed by dual-energy X-ray absorptiometry (DEXA).
      Patients were excluded from the study if they had vertebral fractures revealed by
      radiography, CT scans or MRI. Bisphosphonate (risedronate) was administered for 4
      months. The visual analogue scale (VAS) pain score, Roland Morris Disability
      Questionnaire (RDQ), Short Form-36 (SF-36) questionnaire, BMD and N-terminal
      telopeptide of type I collagen (NTx; a marker for bone resorption) were examined
      before and after treatment. DEXA did not increase significantly, but serum and
      urinary NTx were decreased (-51.4% and -62.0%, respectively) after 4 months of
      risedronate treatment (p<0.01). The assessment was repeated using the VAS score,
      RDQ and SF-36, which revealed an improvement after risedronate treatment
      (p<0.01). A decrease in serum and urinary NTx was associated with improvement of
      low back pain, suggesting that despite the absence of vertebral fractures, bone
      resorption due to osteoporosis may cause low back pain.

PMID- 20044259
TI  - Inhibitory effect of novel tetrahydropyrimidine-2(1H)-thiones on melanogenesis.
AB  - The series of imidazoldine-2-thiones 2 and tetrahydropyrimidine-2-thiones 3 were
      discovered as inhibitor of alpha-MSH-induced melanin production in melanoma B16
      cells. The primary bioassay showed that 1-(4-ethylbenzyl)-tetrahydropyrimidine
      2(1H)-thione 3e (>100% inhibition at 10 microM, IC(50)=1.2 microM) and 1-(4-tert
      butylbenzyl)-tetrahydropyrimidine-2(1H)-thione 3f (>100% inhibition at 10 microM,
      IC(50)=0.76 microM) exhibited potent inhibitory effect against alpha-MSH-induced
      melanin production. Compounds 3 inhibit the biosynthesis of tyrosinase without
      affecting its catalytic activity in melanogenesis.

PMID- 20044260
TI  - The chemical synthesis and antibiotic activity of a diverse library of 2
      aminobenzimidazole small molecules against MRSA and multidrug-resistant A.
      baumannii.
AB  - Multidrug-resistant bacterial infections continue to be a rising global health
      concern. Herein is described the development of a class of novel 2
      aminobenzimidazoles with antibiotic activity. These active 2-aminobenzimidazoles
      retain their antibiotic activity against several strains of multidrug-resistant
      Staphylococcus aureus and Acinetobacter baumannii when compared to susceptible
      strains.

PMID- 20044262
TI  - Half-life measurement of 124Sb.
AB  - The half-life of (124)Sb was determined experimentally by following the decay of
      a source from a radiopure solution with a Centronic IG12 ionisation chamber.
      Thousands of measurements were performed over a period of 358 days, i.e. about
      six half-life periods. However, the data analysis was restricted to the first 221
      days, in order to limit the dominant uncertainty component associated with the
      hypothetical possibility of a systematic error on background subtraction. The
      resulting value for the (124)Sb half-life, 60.212 (11) days, is found to be in
      very good agreement with published values, but carries a lower uncertainty. Major
      uncertainty contributions pertain to possible systematic errors in background
      correction, long-term changes in source-detector geometry and medium- and long
      term instability of the instrument. Additional measurements were performed with a
      high-purity germanium detector to confirm the above value.

PMID- 20044261
TI  - Toosendanin: synthesis of the AB-ring and investigations of its anti-botulinum
      properties (Part II).
AB  - Botulinum neurotoxins (BoNTs) are the etiological agents responsible for
      botulism, a disease characterized by peripheral neuromuscular blockade and a
      characteristic flaccid paralysis of humans. The natural product toosendanin, a
      limonoid, is a traditional Chinese medicine that has reported anti-botulinum
      properties in animal models. Toosendanin effectively inhibits the biological
      activity of BoNT/A in neuronal cells at concentrations of 200 nM, and partial
      inhibition can be observed with concentrations as low as 8 nM. Mechanistically,
      toosendanin's inhibition is due to prevention of transduction of the BoNT LC
      through the HC channel. Intriguing questions as to the molecular architecture of
      toosendanin as related to its anti-botulinum properties have focused our
      attention on a synthesis of toosendanin's unusual AB-ring, containing a unique
      bridged hemi-acetal. Within the current work, a synthetic strategy allowing
      access to the AB-fragment of toosendanin was achieved from a trans-decalin
      system. In addition, this fragment was examined for its modulation of BoNT/A
      intoxication in a rat spinal cord cellular assay.

PMID- 20044263
TI  - Ultra-high resolution mass separator--application to detection of nuclear weapons
      tests.
AB  - A Penning trap-based purification process having a resolution of about 1 ppm is
      reported. In this context, we present for the first time a production method for
      the most complicated and crucially important nuclear weapons test signature,
      (133m)Xe. These pure xenon samples are required by the Comprehensive Nuclear-Test
      Ban Treaty Organization to standardize and calibrate the worldwide network of
      xenon detectors.

PMID- 20044264
TI  - Characterization and partial purification of acyl-CoA:glycerol 3-phosphate
      acyltransferase from sunflower (Helianthus annuus L.) developing seeds.
AB  - The glycerol 3-phosphate acyltransferase (GPAT, EC 2.3.1.15) from sunflower
      (Helianthus annuus L.) microsomes has been characterised and partially purified.
      The in vitro determination of activity was optimized, and the maximum value for
      GPAT activity identified between 15 and 20 days after flowering. The apparent
      Michaelis-Menten K(m) for the glycerol 3-phosphate was 354 muM. The preferred
      substrates were palmitoyl-CoA = linoleoyl-CoA > oleoyl-CoA with the lowest
      activity using stearoyl-CoA. High solubilisation was achieved using 0.75% Tween80
      and the solubilised GPAT was partially purified by ion-exchange chromatography
      using a Hi-Trap DEAE FF column, followed by gel filtration chromatography using a
      Superose 12 HR column. The fraction containing the GPAT activity was analysed by
      SDS-PAGE and contained a major band of 60.1 kDa. Finally, evidence is provided
      which shows the role of GPAT in the asymmetrical distribution, between positions
      sn-1 and sn-3, of saturated fatty acids in highly saturated sunflower
      triacylglycerols. This work provides background information on the sunflower
      endoplasmic reticulum GPAT which may prove valuable for future modification of
      oil deposition in this important crop.

PMID- 20044265
TI  - Non-small-cell lung cancer restaging with transcervical extended mediastinal
      lymphadenectomy.
AB  - BACKGROUND: To analyse a diagnostic yield of the transcervical extended
      mediastinal lymphadenectomy (TEMLA) in restaging of the mediastinal nodes after
      neoadjuvant chemo- or chemo-radiotherapy for non-small-cell lung cancer (NSCLC).
      METHODS: From 1 January 2004 to 30 April 2009, 63 patients who underwent
      induction chemotherapy or chemo-radiotherapy for N2 and N2/3 metastatic nodes
      discovered preoperatively were restaged. There were 12 women and 51 men in the
      age group of 43-71 (mean 57.8) years. There were 45 squamous cell carcinomas, 13
      adenocarcinomas, one pleomorphic carcinoma and four NSCLCs. A total of 54
      patients underwent neoadjuvant chemotherapy and nine chemo-radiotherapy. Seven
      patients had mediastinoscopy before neoadjuvant therapy. As many as 34 patients
      underwent endobronchial ultrasound (EBUS), one patient underwent endo-oesophageal
      ultrasound (EUS) and 10 patients underwent combined EBUS/EUS. The diagnostic
      results of TEMLA were compared with the results of the largest published series
      of restaging patients. The results of subsequent thoracotomies after negative
      TEMLA were presented. RESULTS: There were no serious complications or mortality
      after TEMLA. Metastatic nodes were discovered in 22 patients including three
      patients with N3 nodes and 19 patients with N2 nodes. Stations 7, 4R, 2R and 4L
      were the most prevalent. Of the 63 patients, 42 underwent subsequently
      thoracotomy. Resectability for negative TEMLA was 92.7%. There were 37 R0
      resections and four R1 resections. There was no postoperative mortality, two
      bronchial fistulas were developed (after inferior bilobectomy and right
      pneumonectomy; the second one healed spontaneously) and there were no other
      serious complications. During thoracotomy with completion lymphadenectomy one
      false-negative result was found (single node in station 8). Sensitivity of TEMLA
      in the discovery of N2/3 nodes during restaging was 95.5%, specificity 100%,
      accuracy 98.3%, negative predictive value (NPV) 97.4% and positive predictive
      value (PPV) 100%. TEMLA was found to have significantly better sensitivity and
      NPV (p<0.05) than other series of restaging. During follow-up a local recurrence
      was noted in six of 37 (15.7%) patients after pulmonary resection. CONCLUSIONS:
      (1) The results of TEMLA in restaging of NSCLC (N2/3) patients after induction
      chemotherapy or chemo-radiotherapy were significantly better than those achieved
      with remediastinoscopy, EBUS and positron emission tomography/computed tomography
      (PET/CT). (2) The results of future studies will show if TEMLA should be
      considered the gold standard of mediastinal nodal restaging after neoadjuvant
      therapy in patients with NSCLC.

PMID- 20044266
TI  - Responses in the morphology, physiology and biochemistry of Taxus chinensis var.
      mairei grown under supplementary UV-B radiation.
AB  - The effects of supplemental UV-B radiation on Taxus chinensis var. mairei were
      studied. Leaf traits, gas exchange parameters and the concentrations of
      photosynthetic pigments, cellular defense system products, secondary metabolites
      and ultrastructure were determined. UV-B radiation significantly decreased leaf
      area (p<0.05). Leaf number, secondary branch number, leaf weight per plant and
      leaf moisture all increased dramatically (p<0.05). Neither the leaf weight nor
      the specific leaf weight (SLW) exhibited significant differences between ambient
      and enhanced UV-B radiation. Gas exchange parameters were all dramatically
      reduced by enhanced UV-B radiation (p<0.05). The contents of chlorophyll and the
      chlorophyll a/b ratio were not distinctly affected by UV-B radiation, while
      carotenoids content significantly decreased (p<0.05). Supplemental UV-B treatment
      induced significant flavonoid accumulation (p<0.05), which was able to protect
      plant from radiation damage. Meanwhile, the appendage content, abaxial stomatal
      density, papilla density and particulate matter content in substomatic chambers
      increased noticeably by supplemental UV-B radiation, whereas the aperture size of
      single stomata was diminished. The number and area of plastoglobuli were
      apparently reduced by UV-B radiation, but stroma and grana lamellae were not
      destroyed. Our results demonstrated that T. chinensis var. mairei can activate
      several defense mechanisms against oxidative stress injury caused by supplemental
      UV-B radiation.

PMID- 20044267
TI  - Preoperative radiochemotherapy for resectable localised oesophageal cancer: a
      controversial strategy.
AB  - Preoperative chemoradiation (P-CRT) remains a controversial strategy in the
      treatment of squamous cell cancer (SCC) and adenocarcinoma (ADC) of the
      oesophagus. Until recently, randomised studies mixed the two, often without any
      distinction. In randomised studies involving exclusively SCC, P-CRT increases the
      rate of local control, R0 resection, pCR and disease-free survival. The absence
      of any impact on overall survival may be linked to the toxic effects of this
      treatment. Meta-analyses have revealed a survival benefit of approximately +13%
      at 2 years. However, the methodology used was perhaps questionable. Five
      randomised trials involving ADC patients compared P-CRT with surgery alone. The
      results were contradictory with insufficient statistical power in selected
      positive studies to answer this issue once and for all. P-CRT is unsatisfactory
      as a standard treatment. Although local control rates were increased with P-CRT,
      it should be considered only for selected patients in selected centres.

PMID- 20044268
TI  - Cytokines in bronchoalveolar lavage fluid and serum of lung cancer patients
      during radiotherapy - Association of interleukin-8 and VEGF with survival.
AB  - Radiotherapy (RT) produces oxidative stress and local inflammation. This study
      aimed at clarifying the role of different cytokines (VEGF, TNFalpha, IL-1beta, IL
      6, IL-8, IL-12 and IL-18) in bronchoalveolar lavage (BAL) fluid and in the serum
      of lung cancer patients at baseline and during RT. Bronchoscopy and BAL were
      performed on 36 lung cancer patients and 36 controls for diagnosis; patients
      receiving RT had a second bronchoscopy during RT. Serum samples were obtained
      during RT and three months after RT. In this study lung cancer patients had
      higher levels of serum and BAL fluid IL-6 and serum IL-8 compared to controls
      (p<0.001, p=0.039 and p=0.030, respectively). RT caused a significant increase of
      BAL fluid IL-6 (p=0.037). There were no significant associations between baseline
      cytokine levels and adverse events or response to treatment. Higher baseline
      serum and BAL fluid IL-8 and serum VEGF levels (p=0.036, p=0.027 and p=0.014,
      respectively) were associated with shorter survival. This study shows that lung
      cancer is associated with upregulation of IL-6 and IL-8. The increase of BAL
      fluid IL-6 during RT might be attributed to enhanced RT-related oxidative stress
      or increased cell death. Serum and BAL fluid IL-8 and serum VEGF might have a
      prognostic role in survival of lung cancer.

PMID- 20044269
TI  - Digestion completeness of microwave-assisted and conventional trypsin-catalyzed
      reactions.
AB  - Microwave-assisted proteolytic digestion often yields misscleaved peptides,
      attributed to incomplete hydrolysis reactions between enzymes and substrates. The
      number of missed cleavages is an important parameter in proteome database
      searching. This study investigates how various factors affect digestion
      processes. Optimum conditions for microwave-assisted digestion (50 mM Tris
      buffer, 30 min at 60 degrees C, and enzyme to protein molar ratio of 1:5) were
      determined. The digestion products obtained from eight standard proteins were
      characterized based on matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS). Experimental results indicate that the digestion
      temperature, reaction time, enzyme to substrate ratio, and digestion buffer
      affect the number of misscleaved peptides and incomplete digestion percentages.
      Although all protein molecules in a sample could be digested into peptides within
      a few minutes under microwave irradiation, longer reaction times or methods to
      maximize the enzyme activity should be considered if digestion completeness is a
      major concern.

PMID- 20044270
TI  - Laser desorption/ionization Fourier transform mass spectrometry of thin films
      deposited on silicon by plasma polymerization of acetylene.
AB  - Thin films deposited on silicon substrate by three different methods of plasma
      polymerization of acetylene were analyzed by direct laser desorption/ionization
      Fourier transform mass spectrometry. High-resolution mass spectra showed the
      presence of carbon clusters and hydrocarbon oligomers in different relative
      abundances. During unipolar and continuous discharge polymerization of acetylene
      hydrogen gas mixtures, quadrupole mass spectra of the plasma constituents showed
      the presence of molecular species with m/z lower than 100--mainly peaks of
      C(4)H(2) and C(6)H(2). Films produced had smooth surfaces and the corresponding
      LDI-FTMS spectra displayed only carbon cluster signals in the positive ion mode
      and both hydrocarbon and carbon cluster signals (with much higher relative
      abundance of carbon cluster signals) in the negative ion mode. Alternatively,
      during bipolar discharge with either higher acetylene gas flux (>40 cm(3)/min) or
      longer deposition times (>10 min), quadrupole mass spectra of the plasma
      constituents showed signals corresponding to polycyclic aromatic hydrocarbons
      (PAH) with m/z higher than 100. SEM pictures of the bipolar thin films
      demonstrated the presence of "flower" structures and nanoparticles developed on
      the surface. LDI-FTMS spectra of such thin films showed either total absence or
      lower relative abundance of carbon cluster signals, compared with hydrocarbon
      signals.

PMID- 20044271
TI  - A novel rearrangement of fluorescent human thymidylate synthase inhibitor
      analogues in ESI tandem mass spectrometry.
AB  - Cu(I) catalyzed alkyne-azide cycloaddition reaction was employed to synthesize a
      series of anthracene-based human thymidylate synthase (hTS) inhibitor analogues.
      The triazolo-anthracene derivatives were characterized by ESI-MS/MS and a novel
      rearrangement reaction in ESI-MS/MS was observed. The mechanism is proposed
      whereby the protonated triazolo-anthracene derivative forms a carbocation, and
      then the carbocation electrophilically attacks an anthracene moiety resulting in
      formation of a rearrangement ion. Moreover, the carbocation prefers to attack the
      gamma position rather than the alpha or beta position of the anthracene moiety by
      an electrophilic substitution mechanism.

PMID- 20044272
TI  - Molecular mechanisms of allorecognition in a basal chordate.
AB  - Allorecognition has been described in many metazoan phyla, from the sponges to
      the mammals. In vertebrates, allorecognition is a result of a MHC-based
      recognition event central to adaptive immunity. However, the origin of the
      adaptive immune system and the potential relationship to more primitive
      allorecognition systems is unclear. The colonial ascidian, Botryllus schlosseri,
      has been used as a model organism for the study of allorecognition for over a
      century, as it undergoes a natural transplantation reaction controlled by a
      single, highly polymorphic locus. Herein we will summarize our current
      understanding of the molecular mechanisms that underlie this innate
      allorecognition reaction.

PMID- 20044273
TI  - Investigation of motor unit recruitment during stimulated contractions of
      tibialis anterior muscle.
AB  - This work investigated motor unit (MU) recruitment during transcutaneous
      electrical stimulation (TES) of the tibialis anterior (TA) muscle, using
      experimental and simulated data. Surface electromyogram (EMG) and torque were
      measured during electrically-elicited contractions at different current
      intensities, on eight healthy subjects. EMG detected during stimulation (M-wave)
      was simulated selecting the elicited MUs on the basis of: (a) the simulated
      current density distribution in the territory of each MU and (b) the excitation
      threshold characteristic of the MU. Exerted force was simulated by adding the
      contribution of each of the elicited MUs. The effects of different fat layer
      thickness (between 2 and 8mm), different distributions of excitation thresholds
      (random excitation threshold, higher threshold for larger MUs or smaller MUs),
      and different MU distributions within the muscle (random distribution, larger MU
      deeper in the muscle, smaller MU deeper) on EMG variables and torque were tested.
      Increase of the current intensity led to a first rapid increase of experimental M
      wave amplitude, followed by a plateau. Further increases of the stimulation
      current determined an increase of the exerted force, without relevant changes of
      the M-wave. Similar results were obtained in simulations. Rate of change of
      conduction velocity (CV) and leading coefficient of the second order polynomial
      interpolating the force vs. stimulation level curve were estimated as a function
      of increasing current amplitudes. Experimental data showed an increase of
      estimated CV with increasing levels of the stimulation current (for all subjects)
      and a positive leading coefficient of force vs. stimulation current curve (for
      five of eight subjects). Simulations matched the experimental results only when
      larger MUs were preferably located deeper in the TA muscle (in line with a
      histochemical study). Marginal effect of MU excitation thresholds was observed,
      suggesting that MUs closer to the stimulation electrode are recruited first
      during TES regardless of their excitability.

PMID- 20044274
TI  - Novel 2009 H1N1 influenza virus infection requiring extracorporeal membrane
      oxygenation in a pediatric heart transplant recipient.
AB  - The novel 2009 H1N1 influenza virus has been reported to have increased severity
      in patients with underlying cardiovascular and lung disease. Pediatric patients
      also appear to have an increased incidence of infection. The impact on
      cardiothoracic transplant recipients, especially in pediatric recipients, has not
      been established. We report the case of a 12-year-old boy with history of
      congenital heart disease who was transplanted in June 2001. In October 2009, it
      was found that he had developed severe acute respiratory distress syndrome (ARDS)
      secondary to novel 2009 H1N1 influenza virus. Extracorporeal membrane oxygenation
      (ECMO) was given as support. Importantly, the initial specimen evaluated by real
      time reverse transcriptase-polymerase chain reaction was negative for novel 2009
      H1N1 influenza virus. The patient was successfully weaned from ECMO after 24
      days, extubated at 6 weeks, and continues to make steady rehabilitative progress.
      Early suspicion for infection and initiation of treatment, even with negative
      testing, is essential for cardiothoracic transplant recipients during the current
      pandemic of novel 2009 H1N1 influenza virus.

PMID- 20044275
TI  - Limited prognostic value of cardiac metaiodobenzylguanidine in advanced heart
      failure.

PMID- 20044276
TI  - Long-term outcomes of cadaveric lobar lung transplantation: helping to maximize
      resources.
AB  - BACKGROUND: Cadaveric lobar lung transplantation (CLLTx) represents a potential
      opportunity to address the bias against smaller recipients, especially children,
      on transplant waiting lists. The widespread use of CLLTx is hindered by the
      paucity of outcome data with respect to early complications and long-term lung
      function and survival. METHODS: We looked at the long-term outcomes in 9 patients
      undergoing CLLTx since May 2003, including early surgical complications,
      pulmonary function tests, and survival. Patients were analyzed by whether the
      decision to perform CLLTx was elective (made at the time of listing) or emergent
      (surgical decision). RESULTS: The incidence of early complications in the entire
      group was low, with the most common being atrial arrhythmias and prolonged
      thoracostomy tube. Lung function at 1 and 2 years (mean forced expiratory volume
      in 1 second % predicted +/- standard deviation of 73 +/- 18 and 60.5 +/- 27,
      respectively) was equivalent to living lobar transplant results. Overall survival
      was similar to 199 patients who received conventional cadaveric LTx during the
      same period. CONCLUSION: This study suggests that CLLTx has a low complication
      rate with acceptable lung function and long-term survival, especially in cases
      where consideration has been given to CLLTx at the time of listing. CLLTx
      warrants consideration more often for patients of smaller physique to improve
      their chance of receiving LTx.

PMID- 20044277
TI  - Lipopolysaccharide pre-conditioning is protective in lung ischemia-reperfusion
      injury.
AB  - BACKGROUND: The availability of suitable lung donors has remained a significant
      barrier to lung transplantation. The clinical relevance of an isolated positive
      Gram stain in potential donor lungs, which occurs in >80%, is unclear. Low doses
      of lipopolysaccharide (LPS) have been protective in several models of ischemia
      reperfusion injury through a pre-conditioning response. We sought to demonstrate
      that low-dose LPS is protective against subsequent lung ischemia-reperfusion
      injury. METHODS: Pathogen-free Long-Evans rats were pre-treated with vehicle or
      LPS 24 hours before 90 minutes of ischemia and up to 4 hours of reperfusion.
      Lungs were assessed for vascular permeability, myeloperoxidase content,
      bronchoalveolar lavage inflammatory cell and cytokine/chemokine content, as well
      as nuclear translocation of nuclear factor kappaB (NFkappaB) and activator
      protein-1 (AP-1), and interleukin-1 receptor-associated kinase-1 (IRAK-1) and
      stress-activated protein kinase (SAPK) activation. RESULTS: Compared with
      positive controls, LPS pre-treatment resulted in reductions in vascular
      permeability (70%, p < 0.001), myeloperoxidase content (93%, p < 0.001),
      bronchoalveolar lavage inflammatory cells (91%, p < 0.001), and inflammatory
      cytokine/chemokine content (cytokine-induced neutrophil chemoattractant, 99%, p =
      0.003; interleukin-1beta, 72%, p < 0.0001; tumor necrosis factor-alpha, 76%, p <
      0.0001), NFkappaB (86%, p < 0.001) and AP-1 (97%, p < 0.001) nuclear
      translocation, and IRAK-1 (87%, p < 0.001) and SAPK (80%, p < 0.001)
      phosphorylation. CONCLUSIONS: Lipopolysaccharide pre-treatment reduced lung
      injury and inflammatory mediator production after subsequent exposure to ischemia
      reperfusion. Understanding the clinical significance of lipopolysaccharide in
      donor lungs has the potential to expand and clarify donor inclusion criteria.

PMID- 20044278
TI  - Duration of left ventricular assist device support: Effects on abnormal calcium
      cycling and functional recovery in the failing human heart.
AB  - BACKGROUND: Intracellular Ca(2+) handling is abnormal in human heart failure.
      Studies have demonstrated that left ventricular assist device (LVAD) support
      reverses phenotypic alterations, suggesting that, in select patients, LVAD
      support may be a bridge to recovery. Few studies have related support duration to
      phenotypic recovery. We hypothesized that reversal of impaired sarcoendoplasmic
      reticulum (SR) Ca(2+) cycling following LVAD implantation is duration-dependent.
      METHODS: We used post-rest potentiation to assess SR function, and Western blot
      analysis to measure Ca(2+)-cycling proteins. Left ventricular tissue from 10 non
      failing hearts, 8 failing hearts and 10 LVAD-supported hearts was analyzed.
      Support ranged from 7 to 334 days. The median duration, 115 days, divided
      patients into short- and long-term support groups. RESULTS: Post-rest
      potentiation (PRP) response recovered after short-term LVAD support to a level
      (116.8 +/- 12.1%; n = 5) close to non-failing (123.4 +/- 12.0%; n = 10) hearts,
      but recovery after long-term support (23.5 +/- 7.0%; n = 5) remained closer to
      that of failing hearts (13.5 +/- 5.6%). We found a similar pattern of
      normalization for SR Ca(2+)-ATPase protein and the phospholamban/SR Ca(2+)-ATPase
      ratio (non-failing: 0.66 +/- 0.11; failing: 1.21 +/- 0.23; short-duration LVAD:
      0.68 +/- 0.14; long-duration LVAD: 1.67 +/- 0.30; correlation p < 0.001; r =
      0.93). The ratio also tended to correlate with the PRP response after unloading
      (p = 0.05; r = -0.65). CONCLUSIONS: SR Ca(2+) handling improved during early LVAD
      support, but long-term support was associated with abnormal Ca(2+) cycling. These
      findings cast doubt on strategies designed to wean patients after complete
      unloading with an LVAD.

PMID- 20044279
TI  - Treatment with telmisartan attenuates graft arteriosclerosis in murine cardiac
      allografts.
AB  - BACKGROUND: Chronic rejection remains the most prominent cause of graft failure
      after transplantation. Recently, it was reported that telmisartan can function as
      a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma)
      in addition to a blocker of angiotensin II receptor. We investigated the effect
      of telmisartan on chronic rejection. METHODS: Hearts from Bm12 mice were
      transplanted into C57BL/6 mice (Class II mismatch), and allografts were harvested
      at 8 weeks after transplantation. Recipient mice were fed either control chow or
      chow containing telmisartan (10 mg/kg/day) from 1 day before transplantation.
      Proliferation assays of smooth muscle cells (SMCs), which were isolated from the
      aorta of B/6 mice, was performed. RESULTS: Although severe neo-intimal
      hyperplasia developed in allografts from control mice fed chow (luminal occlusion
      70.9 +/- 6.1%), neo-intimal hyperplasia was significantly attenuated in
      allografts from mice fed chow containing telmisartan (30.0 +/- 10%, p < 0.001).
      Expression of interferon (IFN)-gamma and interleukin (IL)-15 mRNAs and matrix
      metalloproteinase (MMP)-2 in allografts was significantly lower in telmisartan
      treated mice than in control mice. Proliferation of smooth muscle cells (SMCs) in
      response to fetal bovine serum was suppressed significantly by telmisartan (10
      micromol/liter). The PPARgamma antagonist blocked telmisartan-induced suppression
      of SMC proliferation. CONCLUSIONS: Telmisartan attenuates SMC proliferation via
      PPARgamma activity and suppresses neo-intimal hyperplasia after transplantation.
      Telmisartan may be useful for suppressing chronic allograft rejection.

PMID- 20044280
TI  - A regenerative strategy for heart failure in hypoplastic left heart syndrome:
      intracoronary administration of autologous bone marrow-derived progenitor cells.
AB  - Novel surgical strategies have dramatically improved the initial outcome of
      newborns with hypoplastic left heart syndrome. However, the single systemic right
      ventricle remains a major challenge, with limited effectiveness of pharmacologic
      therapy. The present case documents that the intracoronary administration of
      autologous bone marrow-derived progenitor cells is technically feasible in a
      critically ill infant with hypoplastic left heart syndrome and severe heart
      failure after a hybrid comprehensive stage II procedure. Cell therapy might
      represent an option before heart transplantation in children with single
      ventricle physiology presenting with severe heart failure.

PMID- 20044281
TI  - Individual differences in metacontrast masking are enhanced by perceptual
      learning.
AB  - In vision research metacontrast masking is a widely used technique to reduce the
      visibility of a stimulus. Typically, studies attempt to reveal general principles
      that apply to a large majority of participants and tend to omit possible
      individual differences. The neural plasticity of the visual system, however,
      entails the potential capability for individual differences in the way observers
      perform perceptual tasks. We report a case of perceptual learning in a
      metacontrast masking task that leads to the enhancement of two types of adult
      human observers despite identical learning conditions. In a priming task both
      types of observers exhibited the same priming effects, which were insensitive to
      learning. Findings suggest that visual processing of target stimuli in the
      metacontrast masking task is based on neural levels with sufficient plasticity to
      enable the development of two types of observers, which do not contribute to
      processing of target stimuli in the priming task.

PMID- 20044282
TI  - Feline bacterial urinary tract infections: An update on an evolving clinical
      problem.
AB  - Although feline urine is increasingly submitted for bacterial culture and
      susceptibility testing as part of a more general diagnostic work-up for a range
      of presentations in veterinary practice, bacterial urinary tract infections
      (UTIs) are relatively uncommon due to a variety of physical and immunological
      barriers to infection. Culture positive urine is most often obtained from older
      female cats and the clinical history may include hematuria, dysuria and
      pollakiuria, or the infection may be occult. Urinalysis usually reveals hematuria
      and pyuria, and Escherichia coli and Gram-positive cocci are cultured most
      frequently. Most feline UTIs can be successfully treated using oral amoxicillin
      or amoxicillin/clavulanic acid administered for at least 14days, but the
      prevalence of antimicrobial resistance amongst infecting bacterial species is a
      growing concern. There is currently no conclusive information on the safety and
      efficacy of alternative therapeutic agents for the treatment of feline UTIs.

PMID- 20044283
TI  - Protecting against Streptococcus zooepidemicus opportunism: the challenge of
      vaccine design.

PMID- 20044284
TI  - Association between environmental dust exposure and lung cancer in dogs.
AB  - The objective of this study was to investigate the relationship between the
      accumulation of black dust matter in lungs (anthracosis) and primary lung cancer
      in dogs. A retrospective study was carried out on material from 35 dogs with
      primary lung cancer and 160 controls. The amount, histological appearance and
      birefringence of anthracosis were assessed in pulmonary specimens by light
      microscopy, and the odds ratio (OR) calculated for dogs with primary lung cancer.
      The same factors were analysed to identify an association between tumour
      histotype, histological grade, and clinical stage. Papillary adenocarcinoma was
      most commonly diagnosed (45.7%). The majority of tumours were of histological
      grade II, and the lung cancer was more often localised (clinical stage I). An
      increased risk of lung cancer was observed in dogs with higher amounts of
      anthracosis (OR: 2.11, CI 95%: 1.20-3.70; P < 0.01), which suggests an
      association between anthracosis due to inhalation of polluted air and lung cancer
      in dogs.

PMID- 20044285
TI  - Neorickettsia helminthoeca and salmon poisoning disease: a review.
AB  - Neorickettsia helminthoeca is an obligate intra-cytoplasmic bacterium that causes
      salmon poisoning disease (SPD), an acute, febrile, fatal disease of dogs. The
      complex life-cycle of this pathogen involves stages in an intestinal fluke
      (Nanophyetus salmincola), a river snail (Oxytrema silicula), in fish, and in fish
      eating mammals. This complexity has created confusion with respect to the various
      bacterial and parasitic infections associated with the disease and its
      significance in dogs in specific geographical locations has likely to have
      previously been under-estimated. This paper addresses the history, taxonomy,
      microbiology of N. helminthoeca and summarises the pathogenesis, clinical signs
      and pathological features associated with infection. Furthermore, the biological
      cycles, treatment, control, and both public and veterinary health impacts
      associated with this pathogen and the intestinal fluke N. salmincola are
      discussed.

PMID- 20044286
TI  - Reproductive status of captive Loggerhead sea turtles based on serum levels of
      gonadal steroid hormones, corticosterone and thyroxin.
AB  - Serum levels of gonadal steroid hormones, corticosterone and thyroxin (T(4)),
      were monitored monthly in two male and one female captive Loggerhead sea turtles
      (Caretta caretta) over a period of 12 months in 2004 and 3 months in 2006. Ovary
      ultrasonography was performed in April and July 2006. The turtles were kept
      together in an outdoor sea pool in natural temperature and photoperiod conditions
      from May to November, then in separate indoor pools from December to April.
      Circulating hormone levels were measured by radioimmunoassay. Oestradiol levels
      in the female turtle surged significantly in July, as did the progesterone level
      in September. Total testosterone levels were different in both males, but both
      peaked in September. The peaks of oestradiol in the female and testosterone in
      the males did not coincide, both showing delay with respect to the hormone cycle
      described in free-ranging Loggerhead sea turtles. A seasonal pattern in T(4)
      levels was not observed. The three captive turtles showed very low corticosterone
      levels throughout the year, with a September peak coinciding with the peaks of
      progesterone in females and testosterone in males. The results suggested that
      conditions of captivity should be as close as possible to natural conditions
      throughout the entire year since the process of vitellogenesis in this species is
      protracted. Exposure to natural conditions for only a few months is insufficient
      to induce reproduction/oviposition.

PMID- 20044287
TI  - Selective heteronuclear Hartmann-Hahn: a multiple-pulse sequence for selective
      magnetization transfer in the structural elucidation of "isotagged"
      oligosaccharides.
AB  - A new selective heteronuclear Hartmann-Hahn (SHEHAHA) multiple-pulse mixing
      sequence is proposed for the solution structure elucidation of milligram amounts
      of peracetylated oligosaccharides in which the acetyl groups are enriched in
      carbon-13, so-called "isotags". SHEHAHA accomplishes exclusive in-phase
      magnetization transfer between the isotag carbonyl (13)C and the proximal proton
      on the sugar ring. Relayed transfer around the sugar rings by proton-proton TOCSY
      is suppressed, while the heteronuclear transfer from the labeled carbonyl carbon
      to the proximal ring proton is maintained. The sequence is broadband in the sense
      that all acetyl groups simultaneously give good signal transfer to their
      respective nearest proton neighbors. The (1)H-detected spectra have decent
      sensitivity and excellent resolution, giving patterns that unambiguously identify
      common structural subunits in human glycans. Peracetylated maltitol is shown as a
      test case of the method. Lineshapes are pure absorption, allowing facile
      measurement of vicinal proton-proton couplings. Linkage points can be deduced,
      and the 2D correlation spectra may be useful for more ambitious prediction
      algorithms and machine identification by a spectral database.

PMID- 20044288
TI  - Homonuclear dipolar recoupling under ultra-fast magic-angle spinning: probing 19F
      19F proximities by solid-state NMR.
AB  - We describe dipolar recoupling methods that accomplish, at high magic-angle
      spinning (MAS) frequencies, the excitation of double-quantum (DQ) coherences
      between spin-1/2 nuclei. We employ rotor-synchronized symmetry-based pulse
      sequences which are either gamma-encoded or non-gamma-encoded. The sensitivity
      and the robustness to both chemical-shift anisotropy and offset are examined. We
      also compare different techniques to avoid signal folding in the indirect
      dimension of two-dimensional double-quantum<-->single-quantum (DQ-SQ) spectra.
      This comprehensive analysis results in the identification of satisfactory
      conditions for dipolar (19)F-(19)F recoupling at high magnetic fields and high
      MAS frequencies. The utility of these recoupling methods is demonstrated with
      high-resolution DQ-SQ NMR spectra, which allow probing (19)F-(19)F proximities in
      powered fluoroaluminates.

PMID- 20044289
TI  - Mechanical unfolding of bacterial flagellar filament protein by molecular
      dynamics simulation.
AB  - Bacterial flagellum is a nano-scale motility device constructed by self-assembly.
      During construction of the cell-exterior filament (the 'propeller'), subunit
      proteins (called flagellin) are thought to be exported through the hollow
      flagellum to the growing filament tip in an unfolded state. To gain insight into
      the unfolded state preceding any force-spectroscopy experiments on flagellin, we
      employed force-probe molecular dynamics simulations. Two schemes to attain an
      unfolded state suitable for efficient transport were examined: (i) stretching
      flagellin along its length; (ii) unzipping flagellin from its adjacently placed
      termini. Atomic-level unfolding pathways and the mechanical efforts involved
      under each scheme were obtained for the four-domain flagellin from S.
      typhimurium. Flagellin appeared stiffer and required larger unfolding forces when
      stretched as the relative sliding of beta-strands require the breaking of
      multiple hydrogen bonds at once. In contrast, unzipping requires lower unfolding
      forces as it mainly involves unraveling beta-sheets by breaking hydrogen bonds
      one by one.

PMID- 20044290
TI  - Effect of rhGH on the synthesis and secretion of VLDL to lymph and plasma from
      the intestine of the female rat.
AB  - The intravenous administration of rhGH (recombinant human Growth Hormone) to
      fasting female rats causes an increase in the rate of synthesis and secretion of
      VLDL (very low density lipoproteins). This phenomenon has three striking
      characteristics: (1) the demonstration of an unexpected lipogenic effect of rhGH,
      (2) its rapid occurrence after intravenous injection of the hormone and (3) the
      apparent dependence on the levels of circulating estrogens, as deduced by the
      lack of effect of rhGH on males and castrated females. The target tissue for the
      lipogenic effect was traced to the intestine by means of perfusion experiments of
      isolated duodenal loops. Impairment of liver blood supply discarded this tissue
      as the source of VLDL induced by rhGH. After a single dose of rhGH
      (T(1/2)=16min), the increase in plasma TAG (triacylglycerides) levels followed a
      positive exponential course that lasted ca. 3h. The same phenomenon (with no
      significant differences in kinetic parameters) was observed in three other
      experimental circumstances: fasting intact virgin female rats with impaired
      hepatic circulation, perfusion of isolated duodenum and sampling of mesenteric
      lymph. It is assumed that rhGH stimulates the synthesis of TAG and VLDL by the
      physiological mechanisms already present in enterocytes. Because increased plasma
      levels of VLDL and GH have been demonstrated in the last week of rat pregnancy,
      we believe that the reported phenomenon has physiological implications,
      hypothetically associated with fetal lung maturation. As an hypothesis, we
      suggest that the effect of growth hormone (of pituitary or placental origin) on
      the synthesis and secretion of VLDL by enterocytes uses a nongenomic pathway.

PMID- 20044291
TI  - Marked reductions in bioactive insulin-like growth factor I (IGF-I) during
      hemodialysis.
AB  - OBJECTIVE: Hemodialysis (HD) patients lose lean body mass, even when they are
      adequately dialysed. One reason may be a decreased activity of the IGF-system.
      However, data on changes in bioactive IGF-I during HD are sparse. DESIGN: Ten
      stable, non-diabetic HD patients were studied with 30 min intervals during a
      scheduled HD, with blood sampling before (-15 and 0 min), during (4 h) and after
      (1 h) the session. Patients were fasted for at least 6 h before and during the
      study. Arterial and venous blood was sampled for determination of IGF-I
      bioactivity, free and total IGF-I and IGF-II, IGF binding protein-1 (IGFBP-1),
      IGFBP-1 complexed IGF-I and IGFBP-2. RESULTS: Total IGF-I and -II decreased
      marginally (<12%) at the very end of the study (P<0.05). By contrast, at 3 h free
      and bioactive IGF-I had declined by approximately 35% and 50%, respectively, and
      levels remained suppressed for the rest of the study (P<0.05). Concomitantly,
      IGFBP-1 and IGFBP-1:IGF-I complex formation increased 5.0-fold and 2.6-fold,
      respectively (P<0.05). By contrast, IGFBP-2 did not increase as a result of HD.
      No major differences between arterial and venous concentrations were observed.
      CONCLUSION: Despite marginal reductions in total IGF-I and -II, bioactive and
      free IGF-I declined markedly during and after HD. This is likely a consequence of
      the increase in IGFBP-1, sequestering free IGF-I, and reducing bioactive IGF-I.
      Based on the present data we hypothesize that the catabolism induced by HD is in
      part related to the observed reductions in bioactive IGF-I.

PMID- 20044293
TI  - [Karl Landsteiner discovers the blood groups].
AB  - The discovery of ABO blood group was a major step in mastering transfusion
      therapy. Karl Landsteiner (1868-1843) was the author of this discovery. This
      paper retraces the hard career of this American scientist of Austrian origin, and
      describes the circumstances that led his research to the discoveries, which were
      turning points in the history of the immunology.

PMID- 20044292
TI  - Upregulation of elastase activity in aorta in mucopolysaccharidosis I and VII
      dogs may be due to increased cytokine expression.
AB  - Mucopolysaccharidosis I (MPS I) and MPS VII are due to loss-of-function mutations
      within the genes that encode the lysosomal enzymes alpha-l-iduronidase and beta
      glucuronidase, respectively, and result in accumulation of glycosaminoglycans and
      multisystemic disease. Both disorders are associated with elastin fragmentation
      and dilatation of the aorta. Here, the pathogenesis and effect of gene therapy on
      aortic disease in canine models of MPS was evaluated. We found that cathepsin S
      is upregulated at the mRNA and enzyme activity level, while matrix
      metalloproteinase 12 (MMP-12) is upregulated at the mRNA level, in aortas from
      untreated MPS I and MPS VII dogs. Both of these proteases can degrade elastin. In
      addition, mRNA levels for the interleukin 6-like cytokine oncostatin M were
      increased in MPS I and MPS VII dog aortas, while mRNA for tumor necrosis factor
      alpha and toll-like receptor 4 were increased in MPS VII dog aortas. These
      cytokines could contribute to upregulation of the elastases. Neonatal intravenous
      injection of a retroviral vector expressing beta-glucuronidase to MPS VII dogs
      reduced RNA levels of cathepsin S and MMP-12 and aortic dilatation was delayed,
      albeit dilatation developed at late times after gene therapy. A post-mortem aorta
      from a patient with MPS VII also exhibited elastin fragmentation. We conclude
      that aortic dilatation in MPS I and MPS VII dogs is likely due to degradation of
      elastin by cathepsin S and/or MMP-12. Inhibitors of these enzymes or these
      cytokine-induced signal transduction pathways might reduce aortic disease in
      patients with MPS.

PMID- 20044294
TI  - [Total trapeziectomy with suspension and interposition tendinoplasty for
      trapeziometacarpal osteoarthrisis: results at 6.5 years average follow-up].
AB  - OBJECTIVES: Total trapeziectomy remains the main surgical treatment of
      trapeziometacarpal osteoarthritis. Little has been reported on the long-term
      results of this technique. We report in this study our experience with our
      technique of trapeziectomy associated with interposition and suspension
      tendinoplasty using the abductor pollicis longus tendon with 78 months average
      follow-up. METHODS: Eighteen patients (22 thumbs) of 62.7 years average age
      underwent this procedure. According to Dell classification, there were two stage
      II, five stage III and 15 stage IV. Signs of osteoarthritis of the
      scaphotrapezoidal joint were associated in 19 cases. RESULTS: At 78 months
      average follow-up, 73 % of the patients were painfree. Average opposition was 9.4
      out of 10 according to Kapandji, the grip strength was equal to 18.5 kg and the
      key pinch to 4.4 kg. The quick DASH was equal to 20 over 100. Ninety-one percent
      of the patients were satisfied or very satisfied with the results. Space between
      scaphoid and thumb metacarpal was 3.2mm and was down by 27 %. There were only two
      complications related to a reflex sympathetic dystrophy. DISCUSSION AND
      CONCLUSION: Trapeziectomy associated with interposition and suspension
      tendinoplasty gives satisfactory functional results which are maintained with
      follow-up with high satisfaction rate and low complication rate.

PMID- 20044295
TI  - The effects of acoustic flow and mechanical flow on the sonochemical efficiency
      in a rectangular sonochemical reactor.
AB  - Visualization of cavitation behavior in a rectangular sonochemical reactor at 490
      kHz was carried out by a laser sheet technique and the distribution of liquid
      flow was measured by a laser Doppler velocimeter. The pattern of liquid flow and
      distribution of acoustic pressure of the rectangular sonochemical reactor were
      investigated as a function of the input power from 10 to 50 W. The liquid moved
      upward above the transducer at every power. As increasing the input power, the
      random flow out side the cylindrical part above the transducer changed into the
      convective one and the region of the visualized standing wave which was formed in
      the cylindrical part changed with the input power. The position showing the
      sonochemical luminescence exists inside or near the region where the standing
      wave was visualized. Introduction of a stirrer resulted in disturbance of liquid
      flow and expanded the position showing the sonochemical luminescence, but the
      luminescence intensity was weakened. The sonochemical efficiency was enhanced by
      about twice by introduction of the stirrer. From these results, we discussed the
      effects of liquid flow on sonochemical efficiency with and without a stirrer.

PMID- 20044296
TI  - The GIGYF2 variants are not associated with Parkinson's disease in the mainland
      Chinese population.
AB  - In order to determine the prevalence of GIGYF2 (Grb10-Interacting GYF Protein 2)
      variants in the Chinese population and to better understand the association
      between GIGYF2 and Parkinson's disease (PD), we conducted the genetic screening
      of GIGYF2 in the Chinese population. Twelve exonic variants were identified in 52
      familial PD probands and 56 healthy controls. Non-synonymous point variants
      (Thr25Ala, Asn457Th and Pro460Th) were analyzed in 510 PD patients and 481
      healthy controls of Chinese Han ethnicity. The insertion and deletion variants in
      Exon 25 (Ins Q 1212, Ins QQ 1217, Del Q 1210, Del Q 1216 and Del PPQ1217_1219)
      are not related to the onset of familial PD. Our data indicate the GIGYF2
      variants are not associated with PD in the mainland Chinese Population.

PMID- 20044297
TI  - Public places after smoke-free--a qualitative exploration of the changes in
      smoking behaviour.
AB  - The social context of smoking behaviours is explored after the introduction of
      Scottish smoke-free legislation. A longitudinal qualitative study was conducted
      in four contrasting localities. Whilst post-legislation changes in smoking
      behaviour were evident in all four localities, they were most apparent in the
      disadvantaged localities. Changes in the patterns of smoking were linked to the
      ways in which people interacted in social contexts and how people re-negotiated
      habitual smoking behaviours in public spaces. Pre-legislation differences in the
      communities appeared to influence the extent of these changes. Cultural and
      social contexts are important in shaping smoking behaviours and locating change
      within public places.

PMID- 20044298
TI  - Deracemisation methods.
AB  - New methods continue to be developed for the dynamic kinetic resolution (DKR) and
      deracemisation of racemic chiral compounds, in particular alcohols, amines and
      amino acids. Many of the DKR processes involve the combination of an
      enantioselective enzyme, often a lipase or protease, with a metal racemisation
      catalyst. A greater range of ruthenium-based racemisation catalysts is now
      available with some showing good activity for the racemisation of amines that are
      more difficult to epimerise than the corresponding alcohols. In terms of
      deracemisation processes, further improvements have been achieved with the
      deracemisation of alcohols, using combinations of stereocomplementary
      ketoreductases, and additionally transaminases have been applied to the
      deracemisation of racemic amines.

PMID- 20044300
TI  - Host-microbe interactions: bacteria.

PMID- 20044301
TI  - A theoretical and spectroscopic study of conformational structures of piroxicam.
AB  - Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and
      mechanisms of its side effects, mainly the photo-toxicity. In this paper
      fluorescence spectra in non-protic solvents and different polarities were carried
      out along with theoretical calculations. Preliminary potential surfaces of the
      keto and enol forms were obtained at AM1 level of theory providing the most
      stable conformers, which had their structure re-optimized through the B3LYP/CEP
      31G(d,p) method. From the optimized structures, the electronic spectra were
      calculated using the TD-DFT method in vacuum and including the solvent effect
      through the PCM method and a single water molecule near PRX. A new potential
      surface was constructed to the enol tautomer at DFT level and the most stable
      conformers were submitted to the QST2 calculations. The experimental data showed
      that in apolar media, the solution fluorescence is raised. Based on
      conformational analysis for the two tautomers, keto and enol, the results
      indicated that the PRX-enol is the main tautomer related to the drug
      fluorescence, which is reinforced by the spectra results, as well as the
      interconvertion barrier obtained from the QST2 calculations. The results suggest
      that the PRX one of the enol conformers presents great possibility of involvement
      in the photo-toxicity mechanisms.

PMID- 20044299
TI  - The bacterial essence of tiny symbiont genomes.
AB  - Bacterial genomes vary in size over two orders of magnitude. The Mycoplasma
      genitalium genome has historically defined the extreme small end of this
      spectrum, and has therefore heavily informed theoretical and experimental work
      aimed at determining the minimal gene content necessary to support cellular life.
      Recent genomic data from insect symbionts have revealed bacterial genomes that
      are incredibly small-two to four times smaller than M. genitalium-and these tiny
      genomes have raised questions about the limits of genome reduction and have
      blurred the once-clear distinction between autonomous cellular life and highly
      integrated organelle. New data from various systems with symbiotic bacterial or
      archaeal partners have begun to shed light on how these bacteria may function
      with such small gene sets, but major mechanistic questions remain.

PMID- 20044302
TI  - An application of second-order UV-derivative spectrophotometry for study of
      solvolysis of a novel fluocinolone acetonide ester.
AB  - A novel topical corticosteroid FA-21-PhP, 2-phenoxypropionate ester of
      fluocinolone acetonide, has been synthesized in order to investigate the
      possibility of decreasing systemic side effects. In this study model system for
      in vitro solvolytic reaction of FA-21-PhP has been analyzed in ethanol/water
      (90:10, v/v) with excess of sodium hydrogen carbonate. The selected conditions
      have been used as in vitro model for activation of corticosteroid C-21 ester
      prodrug. The second-order derivative spectrophotometric method (DS) using zero
      crossing technique was developed for monitoring ternary mixture of solvolysis.
      Fluocinolone acetonide (FA) as a solvolyte was determined in the mixture in the
      concentration range 0.062-0.312 mM using amplitude (2)D(274.96). Experimentally
      determined LOD value was 0.0295 mM. The accuracy of proposed DS method was
      confirmed with HPLC referent method. Peak area of parent ester FA-21-PhP was used
      for solvolysis monitoring to ensure the initial stage of changes. Linear
      relationship in HPLC assay for parent ester was obtained in the concentration
      range 0.054-0.54 mM, with experimentally determined LOD value of 0.0041 mM.
      Investigated solvolytic reaction in the presence of excess of NaHCO(3) proceeded
      via a pseudo-first-order kinetic with significant correlation coefficients 0.9891
      and 0.9997 for DS and HPLC, respectively. The values of solvolysis rate constant
      calculated according to DS and HPLC methods are in good accordance 0.038 and
      0.043 h(-1), respectively.

PMID- 20044303
TI  - Spectroscopic studies on 3- and 5-formylsalicylic acids and their complexes with
      Fe(III).
AB  - The electronic absorption spectra of 3-formylsalicylic acid (3-fsa) and 5
      formylsalicylic acid (5-fsa) have been studied in different pure and mixed
      solvents. From the pure solvent study, the Einstein transition probabilities
      (A(if) and B(if)), dipole moment (D(if)), oscillator strength (F(if)), life time
      (tau), and the molar extinction coefficient (epsilon) of the absorption bands
      were determined. The hydrogen bonding and orientation energies between solute and
      solvent molecules have been investigated from the mixed solvent spectra. The
      equilibrium constants, pK(a1) and pK(a2), of the two acids have been determined
      spectrophotometrically and a new approximate method for pK(a1) determination is
      suggested. The complex formation between 3-fsa and 5-fsa and Fe(3+) in solution
      has been investigated spectrophotometrically and the stoichiometric ratios of the
      two systems have been determined applying the continuous variation, mole-ratio
      and the slope ratio methods which all showed a 1:1 type of complexes.

PMID- 20044304
TI  - Study on the inclusion interaction of cucurbit[n]urils with sanguinarine by
      spectrofluorimetry and its analytical application.
AB  - The characteristics of host-guest complexation between cucurbit[n]uril (CB[n],
      n=5, 6, 7, 8) and sanguinarine (SA) were investigated by spectrofluorimetry. The
      result showed that CB[n] (n=5, 6, 7, 8) reacted with SA to form an inclusion
      complex. At the optimum reaction conditions, the rectilinear calibration graphs
      were obtained in the range from 0.1 to 2800 ng mL(-1) for the investigated drug,
      with correlation coefficients 0.9998, 0.9997, 0.9999 and 0.9997 and detection
      limits 0.052, 0.26, 0.03 and 0.058 ng mL(-1) using CB[5], CB[6], CB[7], and
      CB[8], respectively. The apparent association constants of the complexes were
      1.23 x 10(4), 6.73 x 10(3), 4.53 x 10(4) and 1.21 x 10(4) L mol(-1), for the
      reagents in the same order. The result demonstrated that CB[7] exhibited a higher
      fluorescence signal than CB[5], CB[6], and CB[8]. The proposed method was
      successfully applied for the determination of the drug in human urine and serum
      samples.

PMID- 20044305
TI  - Spectroscopic investigation of the interaction of p-benzoquinone with casein in
      the solid state.
AB  - The reaction between p-benzoquinone (PBQ) and casein (protein) in the solid state
      was studied. After reaction with protein, the FT-IR spectra showed a new band at
      1215 cm(-1), with an intense sign attributed for casein/PBQ product. An optimum
      amount of PBQ for determination of the product when mixed with casein was 100mg
      and a reaction time of 30 min. The product was stable for a period of 24h after
      the reacting by heating. The interaction of PBQ with casein was investigated by
      FT-IR, reflectance, Raman and EPR spectroscopies. The reaction between PBQ and
      casein in the solid state yields a radical species (p-benzosemiquinone) that it
      is stabilized by the presence of p-biphenolate and p-benzoquinone species in the
      solid state.

PMID- 20044306
TI  - Structural and electronic properties of new fullerene derivatives and their
      possible application as HIV-1 protease inhibitors.
AB  - Density functional theory (DFT) calculations have been carried out at the hybrid
      Becke 3-Lee-Yang-Parr; B3LYP/3-21G** level of theory to study two series of
      hydroxy-chalca-acetic acid-(4-pyrrolidin-1-yl-phenyl) ester [C(60)-C(2)H(4)N-(4
      XCOCH(2)OH)C(6)H(4)] and hydroxy-chalcoacetic acid-[2-(2-hydroxy-acetylchalcanyl)
      4-pyrrolidin-1-yl-phenyl] ester[C(60)-C(2)H(4)N-(3,4-XCOCH(2)OH)C(6)H(4)]. The X
      atom is O, S or Se for the two series. The vibrational spectra, physical,
      chemical, thermodynamics and Quantitative Structure Activity Relationship (QSAR)
      properties of the studied molecules are calculated and discussed. We have
      evaluated these molecules as HIV-1 protease inhibitors based on the hydrogenation
      interaction between the hydroxymethylcarbonyl (HMC) groups and the two aspartic
      acid of the HIV-1 protease active site. Results show that some of the
      investigated fullerene-based derivatives can be considered promising as HIV-1
      protease inhibitors.

PMID- 20044307
TI  - Mononuclear ruthenium(III) complexes containing chelating thiosemicarbazones:
      synthesis, characterization and catalytic property.
AB  - Mononuclear ruthenium(III) complexes of the type [RuX(EPh(3))(2)(L)] (E=P or As;
      X=Cl or Br; L=dibasic terdentate dehydroacetic acid thiosemicarbazones) have been
      synthesized from the reaction of thiosemicarbazone ligands with ruthenium(III)
      precursors, [RuX(3)(EPh(3))(3)] (where E=P, X=Cl; E=As, X=Cl or Br) and
      [RuBr(3)(PPh(3))(2)(CH(3)OH)] in benzene. The compositions of the complexes have
      been established by elemental analysis, magnetic susceptibility measurement, FT
      IR, UV-vis and EPR spectral data. These complexes are paramagnetic and show
      intense d-d and charge transfer transitions in dichloromethane. The complexes
      show rhombic EPR spectra at LNT which are typical of low-spin distorted
      octahedral ruthenium(III) species. All the complexes are redox active and display
      an irreversible metal centered redox processes. Complex [RuCl(PPh(3))(2)(DHA
      PTSC)] (5) was used as catalyst for transfer hydrogenation of ketones in the
      presence of isopropanol/KOH and was found to be the active species.

PMID- 20044308
TI  - Preparation, characterization and biological activity of novel metal-NNNN donor
      Schiff base complexes.
AB  - Novel Schiff base (H(2)L) ligand is prepared via condensation of benzil and
      triethylenetetraamine. The ligand is characterized based on elemental analysis,
      mass, IR and (1)H NMR spectra. Metal complexes are reported and characterized
      based on elemental analyses, IR, (1)H NMR, solid reflectance, magnetic moment,
      molar conductance, and thermal analyses (TG, DTG and DTA). 1:1 [M]:[H(2)L]
      complexes are found from the elemental analyses data having the formulae
      [M(H(2)L)Cl(2)]xyH(2)O (M=Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cd(II)),
      [Fe(H(2)L)Cl(2)]ClxH(2)O, [Th(H(2)L)Cl(2)]Cl(2)x3H(2)O and
      [UO(2)(H(2)L)](CH(3)COO)(2)x2H(2)O. The metal chelates are found to be non
      electrolytes except Fe(III), Th(IV) and UO(2)(II) complexes are electrolytes. IR
      spectra show that H(2)L is coordinated to the metal ions in a neutral
      tetradentate manner with 4Ns donor sites of the two azomethine N and two NH
      groups. The geometrical structures of these complexes are found to be octahedral.
      The thermal behaviour of these chelates is studied where the hydrated complexes
      lose water molecules of hydration in the first step followed immediately by
      decomposition of the anions and ligand molecules in the subsequent steps. The
      activation thermodynamic parameters are calculated using Coats-Redfern method.
      The ligand (H(2)L), in comparison to its metal complexes, is screened for its
      antibacterial activity. The activity data show that the metal complexes have
      antibacterial activity more than the parent Schiff base ligand and cefepime
      standard against one or more bacterial species.

PMID- 20044310
TI  - Antidepressant action of melatonin in the treatment of Delayed Sleep Phase
      Syndrome.
AB  - BACKGROUND: Depression is a common problem in patients with Delayed Sleep Phase
      Syndrome (DSPS). This study used a randomized, double-blind, crossover, placebo
      controlled approach to test the hypothesis that exogenous melatonin (5mg) can
      attenuate depressive symptomatology in DSPS patients. METHODS: Twenty patients
      with an established diagnosis of DSPS were dichotomized into DSPS with depressive
      symptoms (Group I; n=8) and without depressive symptoms (Group II; n=12) based on
      structured clinical interviews and a score greater than 17 on Center for
      Epidemiologic Studies Depression Scale (CES-D). Both groups received melatonin
      and placebo treatment for 4 weeks with a 1-week washout period in between.
      Participants underwent a clinical interview and psychometric evaluation to assess
      depression, and overnight polysomnographic sleep studies were carried out at
      baseline and at the end of melatonin and placebo treatments. Furthermore,
      melatonin secretion rhythm as a circadian phase marker was assessed by measuring
      urinary 6-sulphatoxymelatonin levels. RESULTS: Melatonin treatment significantly
      reduced depression scores in the depressed patients as measured by the CES-D and
      Hamilton Depression Rating Scale--17. Melatonin treatment improved sleep
      continuity in both groups compared to placebo and baseline conditions. Group I
      individuals showed marked alterations in melatonin rhythms compared to Group II
      individuals. CONCLUSION: Exogenous melatonin treatment may be an effective
      treatment modality for individuals with circadian rhythm sleep disorders and
      associated comorbid depressive symptomatology.

PMID- 20044309
TI  - Linear and nonlinear information flow based on time-delayed mutual information
      method and its application to corticomuscular interaction.
AB  - OBJECTIVE: To propose a model-free method to show linear and nonlinear
      information flow based on time-delayed mutual information (TDMI) by employing uni
      and bi-variate surrogate tests and to investigate whether there are
      contributions of the nonlinear information flow in corticomuscular (CM)
      interaction. METHODS: Using simulated data, we tested whether our method would
      successfully detect the direction of information flow and identify a relationship
      between two simulated time series. As an experimental data application, we
      applied this method to investigate CM interaction during a right wrist extension
      task. RESULTS: Results of simulation tests show that we can correctly detect the
      direction of information flow and the relationship between two time series
      without a prior knowledge of the dynamics of their generating systems. As
      experimental results, we found both linear and nonlinear information flow from
      contralateral sensorimotor cortex to muscle. CONCLUSIONS: Our method is a viable
      model-free measure of temporally varying causal interactions that is capable of
      distinguishing linear and nonlinear information flow. With respect to
      experimental application, there are both linear and nonlinear information flows
      in CM interaction from contralateral sensorimotor cortex to muscle, which may
      reflect the motor command from brain to muscle. SIGNIFICANCE: This is the first
      study to show separate linear and nonlinear information flow in CM interaction.

PMID- 20044311
TI  - Phylogenetic affiliations of mesopelagic acantharia and acantharian-like
      environmental 18S rRNA genes off the southern California coast.
AB  - Incomplete knowledge of acantharian life cycles has hampered their study and
      limited our understanding of their role in the vertical flux of carbon and
      strontium. Molecular tools can help identify enigmatic life stages and offer
      insights into aspects of acantharian biology and evolution. We inferred the
      phylogenetic position of acantharian sequences from shallow water, as well as
      acantharian-like clone sequences from 500 and 880 m in the San Pedro Channel,
      California. The analyses included validated acantharian and polycystine sequences
      from public databases with environmental clone sequences related to acantharia
      and used Bayesian inference methods. Our analysis demonstrated strong support for
      two branches of unidentified organisms that are closely related to, but possibly
      distinct from the Acantharea. We also found evidence of acantharian sequences
      from mesopelagic environments branching within the chaunacanthid clade, although
      the morphology of these organisms is presently unknown. HRP-conjugated probes
      were developed to target Acantharea and phylotypes from Unidentified Clade 1
      using Catalyzed Reporter Deposition Fluorescence In Situ Hybridization (CARD
      FISH) on samples collected at 500 m. Our CARD-FISH experiments targeting
      phylotypes from an unidentified clade offer preliminary glimpses into the
      morphology of these protists, while a morphology for the aphotic acantharian
      lineages remains unknown at this time.

PMID- 20044312
TI  - The effect of a self-management intervention to reduce vascular risk factors in
      patients with manifestations of vascular diseases.
AB  - BACKGROUND: Self-management can improve health behaviors and influence reduction
      of vascular risk. We developed a 1-year self-management intervention and
      investigated its effect on vascular risk factors and quality of life in patients
      with different vascular diseases. DESIGN AND METHODS: This observational cohort
      study involved 223 patients (self-management group, n=125; usual care group n=98)
      with at least two modifiable vascular risk factors. RESULTS: Patients in the self
      management group achieved treatment goals for LDL-cholesterol (difference 13%;
      95%CI 1-26) and HDL-cholesterol (difference 9% 95%CI 0-19) significantly more
      often than did patients in the usual care group. Mean systolic blood pressure
      decreased significantly by 5mm Hg (95%CI -9 to 0) in the self-management group
      and mean BMI increased significantly by 0.4 kg/m(2) (95%CI -0.8 to -0.1) in the
      usual care group. No significant differences were seen in waist circumference,
      smoking, or triglycerides. General health (RAND36) improved more in the self
      management group (by 8 points 95%CI 3-12) than in the usual care group.
      CONCLUSION: After 1 year, the self-management intervention was more effective
      than usual care on several important vascular risk factors in patients with
      vascular diseases. PRACTICE IMPLICATIONS: This self-management intervention used
      in a hospital population may be applicable in different care settings.

PMID- 20044313
TI  - Bladder hemangiomas and Proteus syndrome: a rare clinical association.
AB  - A case of bladder hemangiomas in association with Proteus syndrome (PS) is
      described. PS is a rare hamartomatous disorder and comprises an association of
      verrucous epidermal nevi, infantile hemangiomas, lipoma-like subcutaneous
      hamartomas and asymmetrical overgrowth of almost any part of the body. To our
      knowledge, this is the second case reported of hematuria associated with bladder
      hemangiomas in PS.

PMID- 20044314
TI  - A common strategy and database to compare the performance of seizure prediction
      algorithms.
AB  - A reliable algorithm for the timely prediction of epileptic seizures would be a
      milestone in epilepsy research. Prediction performances have so far been
      determined using retrospective data assessment, leaving open the question as to
      whether they prove statistically significant and clinically useful under
      prospective conditions. To this aim, a Seizure Prediction Competition has been
      set up. Here, the background and the details of this competition are described.

PMID- 20044315
TI  - Using behavioral interventions to assist with routine procedures in children with
      cystic fibrosis.
AB  - Routine cystic fibrosis (CF) medical care includes invasive procedures that may
      be difficult for young children and adolescents to tolerate because of anxiety,
      concern with health status, or unfamiliarity with the performed tasks. A growing
      body of pediatric psychology literature suggests that behavior therapy can
      effectively increase patient cooperation with stressful medical procedures such
      as tracheostomy care and needle sticks. Throat cultures are obtained at least
      quarterly in the outpatient setting or more frequently if a CF patient develops
      respiratory symptoms. Obtaining a throat culture from an anxious and
      uncooperative child poses a significant challenge for physicians, since the child
      may demonstrate emotional distress and avoidant behavior that disrupts efficient
      specimen collection during a routine clinic visit. The use of behavioral
      interventions, such as relaxation exercises, diaphragmatic breathing,
      differential reinforcement, gradual exposure, and systematic desensitization, is
      beneficial in addressing this commonly encountered problem in CF care. This case
      series describes the implementation of a behavioral therapy protocol utilizing
      two interventions, gradual exposure and systematic desensitization, in two young
      CF patients for the treatment of behavioral distress with routine throat
      cultures. The behavioral interventions were simple and transferred easily from
      mock procedures to actual specimen collection. Moreover, these cases highlight
      the important roles of the pediatric psychology staff on a comprehensive
      multidisciplinary CF care team to improve patient cooperation with routine clinic
      procedures and the medical treatment regimen overall.

PMID- 20044316
TI  - Performance of tiloronoxim and tilorone determination in human blood by HPLC
      MS/MS: method validation, uncertainty assessment and its application to a
      pharmacokinetic study.
AB  - A highly sensitive and selective HPLC-MS/MS method is presented for the
      quantitative determination of tiloronoxim and its metabolite tilorone in human
      blood. An aliquot of 200 microl human blood was extracted with a mixture of
      chloroform/ethyl ether (1/2, v/v), using metoprolol as the internal standard (the
      IS). Separation was achieved on an Xterra MS C18 column (50 mm x 2.1 mm, 5
      microm) with a gradient mobile phase of methanol/water containing 15 mM ammonium
      bicarbonate (pH 10.5). Detection was performed using positive MRM mode on a
      TurboIonSpray source. The mass transitions monitored were m/z 426.3-->100.0, m/z
      411.3-->100.0 and m/z 268.3-->116.1 for tiloronoxim, tilorone and the IS,
      respectively. The method was fully validated using total error theory, which is
      based on beta-expectation tolerance intervals and include trueness and
      intermediate precision. The method was found to be accurate over a concentration
      range of 1-100 ng/ml for both compounds. The measurement uncertainty based on
      beta-expectation tolerance intervals was assessed at each concentration level of
      the validation standards. This method was successively applied to a
      pharmacokinetic study of tiloronoxim in healthy volunteers.

PMID- 20044317
TI  - Analysis of [(2)H7]methionine, [(2)H4]methionine, methionine, [(2)H4]homocysteine
      and homocysteine in plasma by gas chromatography-mass spectrometry to follow the
      fate of administered [(2)H7]methionine.
AB  - Homocysteine plays a key role in several pathophysiological conditions. To assess
      the methionine-homocysteine kinetics by stable isotope methodology, we developed
      a simultaneous quantification method of [(2)H(7)]methionine, [(2)H(4)]methionine,
      methionine, [(2)H(4)]homocysteine and homocysteine in rat plasma by gas
      chromatography-mass spectrometry (GC-MS). [(13)C]Methionine and
      [(13)C]homocysteine were used as analytical internal standards to account for
      losses associated with the extraction, derivatization and chromatography. For
      labeled and non-labeled homocysteine measurements, disulfide bonds between
      homocysteine and other thiols or proteins were reduced by dithiothreitol. The
      reduced homocysteine and methionine species were purified by cation-exchange
      chromatography and derivatized with isobutyl chlorocarbonate in water-ethanol
      pyridine. Quantification was carried out by selected ion monitoring of the
      molecular-related ions of N(O,S)-isobutyloxycarbonyl ethyl ester derivatives on
      the chemical ionization mode. The intra- and inter-day precision of the assay was
      less than 6% for all labeled and non-labeled methionine and homocysteine species.
      The method is sensitive enough to determine pharmacokinetics of labeled
      methionine and homocysteine.

PMID- 20044318
TI  - A liquid chromatographic-mass spectrometric (LC-MS) method for the analysis of
      the bis-pyridinium oxime ICD-585 in plasma: application in a guinea pig model.
AB  - In recent animal studies, several novel oxime compounds that are better than 2
      PAM as antidotes against selected organophosphate (OP) nerve agents have been
      identified. The purpose of this study was to develop and validate a liquid
      chromatographic-mass spectrometric (LC-MS) method for analysis of the bis
      pyridinium oxime ICD-585 (1-(2-hydroxyiminomethylpyridinium)-3-(4
      carbamoylpyridinium)-propane) in plasma and to establish the utility of the
      method in a guinea pig model. Calibration curves were prepared using ICD-585
      spiked plasma at concentrations from 0.156 to 10 microg/ml. Curves were run over
      a 1-month time frame and a total of 13 (n=13) were generated. The lower limit of
      quantification (LLOQ) was determined to be 0.216 microg/ml. Intra- and inter-day
      variability was assessed by studying precision and accuracy. For intra-day
      studies, data from the precision determinations indicated that the % CV's ranged
      from 4.28 to 14.98%. The % error in the accuracy assessments ranged from -8.73 to
      4.61%. For inter-day studies, precision data ranged from 3.53 to 13.20%. The %
      error in the accuracy assessments ranged from 0.39 to 13.77%. Room temperature,
      freeze-thaw and autosampler stability was also examined. For all 3 stability
      studies, the compound remained within +/-15% of the initial analysis. Application
      of the method was demonstrated by analyzing samples from guinea pigs challenged
      with sarin (GB) or cyclosarin (GF) (1x LD(50)) followed with intramuscular ICD
      585 (58 microM/kg, 21.8 mg/kg). At 55 min after oxime administration, mean (+/
      SD) plasma concentrations were 15.98 (+/-4.88)microg/ml and 14.57 (+/-3.70)
      microg/ml in GB- and GF-exposed animals, respectively. In summary, studies have
      been carried out to verify the sensitivity, precision and accuracy of the assay
      as well as the stability of the analyte under various conditions. The method has
      been demonstrated to be applicable to the analysis of plasma from nerve agent
      exposed guinea pigs.

PMID- 20044319
TI  - Distribution of adipose-derived stem cells in adipose tissues from human
      cadavers.
AB  - BACKGROUND: Adipose-derived stem cells (ASCs) possess multipotency in vivo and in
      vitro, and thus are thought to be very promising precursors for use in
      regenerative medicine. ASCs can be concentrated from adipose tissue by enzymatic
      digestion and transplanted to increase angiogenesis or for cosmesis. ASC
      transplants are now being performed in a clinical setting. Although data on ASCs
      are extensive, the distribution of ASCs in human fat tissue has not been fully
      clarified. Thus, it is important to identify the distribution of ASCs to obtain
      cell populations rich in ASCs for clinical use. METHODS: ASCs express CD34, a
      cell surface marker. As CD34 is also expressed by endothelial cells, we
      immunohistochemically stained 2-MUm-thick serial paraffin sections of fat tissue
      obtained from various parts of formalin-fixed cadavers with anti-CD31 and anti
      CD34 antibodies to distinguish ASCs from endothelial cells. RESULTS:
      CD34(+)/CD31(-) cells were mainly found in connective tissue tracts and
      perivascularly. Among fat tissues obtained from various sites, fat tissues in the
      thoracic back and lower abdomen were richest in CD34(+)/CD31(-) cells.
      CONCLUSION: The concentrations of CD34(+)/CD31(-) cells in adipose tissues differ
      between sites. The sites most highly enriched for ASCs were identified, and it is
      now possible to select the best sites for collection of ASCs for transplantation.

PMID- 20044320
TI  - Post-polio syndrome and rehabilitation.
AB  - Post-polio syndrome (PPS) is the commonly affected term to describe the symptoms
      that may develop many years after acute paralytic poliomyelitis. The etiology of
      PPS is still unclear. An overuse of enlarged motor units is suspected causing
      denervation again due to distal degeneration of axons. Metabolic and functional
      changes has been described in muscle fibers of partially denervated muscles.
      Nevertheless, submaximal aerobic training and low intensity muscular
      strengthening have shown positive effects on muscular strength and
      cardiorespiratory system in patients affected by PPS. Aquatic therapy has a
      positive impact on pain and muscle function. In patients with severe fatigue, it
      is recommended to adapt the daily exercise routine to their specific case.

PMID- 20044321
TI  - Breast cancer screening among Asian immigrant women in Canada.
AB  - OBJECTIVE: The objective of this study was to examine the pattern of breast
      cancer screening among Asian immigrant women aged 50-69 years and compare it with
      corresponding non-immigrant women in Canada. METHODS: Data from the Canadian
      Community Health Survey cycle 2.1 (2003) were utilized. Self-reported screening
      histories were used as outcome variables: socioeconomic status and medical
      histories were used as predictive variables. Analyses were weighted to represent
      the target population. Multivariate logistic regression analyses were performed
      to compare the screening pattern among Asian immigrant women and corresponding
      non-immigrant Canadians. RESULTS: In total, 508 Asian immigrant women were
      included in this study. The results suggest that 71% and 60% of Asian immigrant
      women reported ever having had and recent mammogram use, respectively, while the
      corresponding figures for non-immigrant women were 89% and 72%. The observed
      differences were statistically significant and could not be explained by
      confounding factors. The ability to speak one of the two official languages is an
      important barrier to mammography screening among Asian immigrant women.
      CONCLUSION: The findings show lower rates of mammography screening among Asian
      immigrant women in Canada. If breast screening is to remain a health policy
      objective in Canada, targeted efforts to increase the recruitment of Asian
      immigrant women need to be developed or strengthened.

PMID- 20044322
TI  - AACE and ACRE: Commonality of Interests.

PMID- 20044323
TI  - AACE and ACRE: Harmony of Interests.

PMID- 20044324
TI  - Summary of the ACRE inaugural meeting.
AB  - The charter meeting of the Association of Clinical Researchers and Educators
      (ACRE) provided a powerful set of arguments against assertions that physician
      industry collaboration is harmful and represents a "conflict of interest." Such
      collaboration has, in fact, improved medical care for patients, a case made
      overwhelmingly by patients and patient advocacy groups at the meeting. The
      contentions that physician-industry collaboration is problematic are not based on
      evidence. They depend on unjustified generalization from inevitable, sometimes
      egregious, but vanishingly uncommon adverse outcomes of industry-physician
      interaction without reference to how so much more commonly these interactions add
      value. Furthermore, the claim that physician-industry collaboration is
      unprofessional is refuted by rational scrutiny. Indeed, the term "conflict of
      interest" itself is vague, inviting subjectivity and deserving to be rejected.
      The unwarranted success of conflict of interest regulation has prevailed because
      of the failure of physicians, educators, and innovators, through apathy and
      intimidation, to pay attention to its fallacies and resist its dangers. It has
      arisen from activist ambitions and from misalignment between the purposes of
      medical practitioners, educators, and innovators and those of administrators in
      medical journals and in academic medical centers. The media and politicians have
      not appreciated these misalignments and have accepted conflict of interest
      arguments at face value. Regulation emanating from conflict of interest criticism
      is confusing, onerous, expensive, disrespectful, and damaging. Prohibitions
      against speaking about medical products inhibit physician and patient education
      concerning rapidly emerging and complex therapies. Input by physicians cognizant
      of compliance requirements into such presentations should be encouraged.
      Restrictions to the free flow of corporate support of academic health centers,
      professional societies, and patient organizations threaten to delay medical
      innovation and education.

PMID- 20044325
TI  - Arbitrary "relaxation" of guidelines for inpatient glycemic control?

PMID- 20044327
TI  - Feasibility and effects of a tai chi self-help education program for Korean
      gastric cancer survivors.
AB  - PURPOSE/OBJECTIVES: To determine the feasibility of conducting a study of a tai
      chi self-help education program in Korean adults with gastric cancer and to
      describe the effects of a six-month tai chi self-help education program on
      depression, health-related quality of life (HRQOL), and immune markers. DESIGN:
      One-group, pre- and post-test design. SETTING: Outpatient clinics of two large
      hospitals in the Republic of Korea. SAMPLE: Convenience sample of 33 Korean
      adults with gastric cancer diagnoses after gastrectomy. METHODS: The Korean
      gastric cancer survivors participated in a 24-week tai chi self-help education
      program. The participants completed the Center for Epidemiologic Studies
      Depression (Korean version) and the Functional Assessment of Cancer Therapy
      General (Korean version) for HRQOL and provided blood samples for immune markers.
      All measurements were conducted at baseline and at one week following the 24-week
      intervention. MAIN RESEARCH VARIABLES: Feasibility was determined as the
      percentage of participants completing the 24-week protocol. Preliminary data on
      depression, HRQOL, and immune markers were obtained. FINDINGS: The dropout rate
      was 36.4%; 21 of 33 survivors participated in the tai chi self-help education
      program for 24 weeks. No complications or injuries occurred to the participants
      during the program. No significant differences were noted in depression, HRQOL,
      and immune markers before and after the intervention. CONCLUSIONS: Tai chi
      exercise, in combination with a self-help program, can be safe and feasible for
      Korean gastric cancer survivors. This feasibility study did not show that the tai
      chi self-help education program improves depression, HRQOL, and immune markers in
      Korean gastric cancer survivors. IMPLICATIONS FOR NURSING: Additional studies are
      needed to determine the long-term impact relative to usual care.

PMID- 20044328
TI  - Symptom clusters in children and adolescents receiving cisplatin, doxorubicin, or
      ifosfamide.
AB  - PURPOSE/OBJECTIVES: To examine the influence of the proposed symptom cluster of
      fatigue, nausea and vomiting, and sleep disturbances on clinical outcomes defined
      as behavior changes, depression, and performance status in children and
      adolescents before and after receiving cisplatin, doxorubicin, or ifosfamide
      chemotherapy. DESIGN: A prospective, descriptive, within-group, before-and-after
      chemotherapy design was used. SETTING: Two major childhood cancer treatment
      hospitals in the United States. SAMPLE: 67 patients aged 7-18 years who were
      receiving chemotherapy courses of cisplatin, doxorubicin, or ifosfamide. METHODS:
      Fatigue, depression, behavior, and performance assessments were completed on the
      first day of cisplatin, doxorubicin, or ifosfamide therapy and one week later.
      Patients wore a wrist actigraph on the nondominant hand during the course of
      therapy and for 48 hours after discharge from the hospital. Nausea and vomiting
      were measured every 24 hours during the course of therapy and for 48 hours after
      discharge. A linear mixed model was used to evaluate the influence of the symptom
      cluster. Regression analysis was used to examine the associations between
      performance status and the symptom cluster. Principal component analysis with
      varimax rotation was used to produce the correlation of sleep symptoms. MAIN
      RESEARCH VARIABLES: Fatigue, nausea and vomiting, sleep disturbances, behavior,
      depression, and performance. FINDINGS: Adolescents with the cluster of increased
      fatigue and sleep disturbances experienced more depressive symptoms and behavior
      changes. Children with higher levels of fatigue had increased depressive
      symptoms. The more fatigue parents perceived in their children or adolescents,
      the more behavior and emotional difficulties were reported. CONCLUSIONS: Fatigue,
      sleep disturbance, and nausea and vomiting, when clustered, impacted depressive
      symptoms and behavior changes in adolescents after chemotherapy. In children,
      fatigue alone impacted depressive symptoms and behavior changes. IMPLICATIONS FOR
      NURSING: Symptom clusters can have a significant impact on children's and
      adolescents' quality of life during cancer treatment. Early recognition and
      intervention for these symptoms are an important nursing role.

PMID- 20044329
TI  - Confronting the unexpected: temporal, situational, and attributive dimensions of
      distressing symptom experience for breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To describe women's unexpected and distressing symptom
      experiences after breast cancer treatment. RESEARCH APPROACH: Qualitative and
      descriptive. SETTING: Depending upon their preference, participants were
      interviewed in their homes or in a private office space in a nearby library.
      PARTICIPANTS: Purposive sample of 13 women 1-18 years after breast cancer
      treatment. METHODOLOGIC APPROACH: Secondary analysis of phenomenologic data
      (constant comparative method). MAIN RESEARCH VARIABLES: Breast cancer symptom
      distress, ongoing symptoms, and unexpected experiences. FINDINGS: Women described
      experiences of unexpected and distressing symptoms in the years following breast
      cancer treatment. Symptoms included pain, loss of energy, impaired limb movement,
      cognitive disturbance, changed sexual experience, and lymphedema. Four central
      themes were derived: living with lingering symptoms, confronting unexpected
      situations, losing precancer being, and feeling like a has-been. Distress
      intensified when women expected symptoms to disappear but symptoms persisted
      instead. Increased distress also was associated with sudden and unexpected
      situations or when symptoms elicited feelings of loss about precancer being and
      feelings of being a has been. Findings suggest that symptom distress has
      temporal, situational, and attributive dimensions. CONCLUSIONS: Breast cancer
      survivors' perceptions of ongoing and unexpected symptoms have important
      influences on quality of life. Understanding temporal, situational, and
      attributive dimensions of symptom distress empowers nurses and healthcare
      professionals to help breast cancer survivors prepare for subsequent ongoing or
      unexpected experiences in the years after breast cancer treatment.
      INTERPRETATION: Follow-up care for breast cancer survivors should foster dialogue
      about ways that symptoms might emerge and that unexpected situations might occur.
      Prospective studies are needed to examine symptom distress in terms of temporal,
      situational, and attributive dimensions and explore the relationship between
      symptom distress and psychological distress after breast cancer treatment.

PMID- 20044330
TI  - Do oncology nurses provide more care to patients with high levels of emotional
      distress?
AB  - PURPOSE/OBJECTIVES: To investigate nurses' planning and implementation of
      individualized patient care in relation to patients' emotional distress as
      assessed by nurses and whether nurses and patients perceived the implemented care
      in a similar manner. DESIGN: Prospective, comparative. SETTING: Five oncologic
      hematologic wards in Sweden. SAMPLE: 90 individual nurse-patient pairs were
      recruited and 81 were intact after three consecutive days. Each pair consisted of
      a patient with cancer and a nurse responsible for that patient's care. METHODS:
      Nurse-patient pairs were followed using questionnaires. Outcome measures were
      nurses' identification of patients' emotional distress, care planning, and nurse
      patient ratings of implemented care. MAIN RESEARCH VARIABLES: Patients' emotional
      distress and nurses' implemented care. FINDINGS: Nurses identified a variety of
      emotional issues among patients and planned individual nursing interventions.
      Nurse and patient perceptions of implemented care demonstrated weak correlations
      for individually planned interventions and nurses' general caring behavior. With
      one exception, nurse self-reports did not indicate any differences in nurses'
      caring behavior directed to more and less distressed patients. Nurses reported
      providing comfort more frequently to patients with high levels of emotional
      distress, but this was not substantiated in patients' ratings. CONCLUSIONS:
      Nurses showed an intention to provide individualized care. However, with one
      exception, nurses did not report providing more care to patients with cancer with
      high levels of emotional distress than to less distressed patients. IMPLICATIONS
      FOR NURSING: To ensure individualized care, nurses in cancer care should closely
      validate the accuracy of their interpretation of patients' needs and their
      planning of care in collaboration with the patients.

PMID- 20044331
TI  - Associations between oncology nurses' attitudes toward death and caring for dying
      patients.
AB  - PURPOSE/OBJECTIVES: To examine relationships between oncology nurses' attitudes
      toward death and caring for dying patients. DESIGN: Cross-sectional, descriptive,
      and correlational. SETTING: Israeli Oncology Nurses Society annual conference in
      June 2006. SAMPLE: A convenience sample of 147 Israeli nurses who were exposed to
      death in their daily work. Most worked in oncology departments and were of Jewish
      faith. METHODS: Completion of the Frommelt Attitude Toward Care of the Dying
      Scale, Death Attitude Profile-Revised Scale, and a demographic questionnaire.
      MAIN RESEARCH VARIABLES: Attitudes toward caring for dying patients, attitudes
      toward death (fear of death, death avoidance, and types of death acceptance), and
      demographic variables (e.g., religiosity). FINDINGS: Nurses demonstrated positive
      attitudes toward care of dying patients. The attitudes were significantly
      negatively correlated with death avoidance, fear of death, and approach
      acceptance of death. A mediating role of death avoidance was found between fear
      of death and attitudes toward caring for dying patients. CONCLUSIONS: Nurses'
      personal attitudes toward death were associated with their attitudes toward the
      care of dying patients. The mediating model suggests that some nurses may use
      avoidance to cope with their own personal fears of death. Inconsistency between
      the current results and previous studies of associations between acceptance of
      death and attitudes toward care for dying patients imply that culture and
      religion might play important roles in the development of these attitudes.
      IMPLICATIONS FOR NURSING: Training and support programs for oncology nurses
      should take into consideration nurses' personal attitudes toward death as well as
      their religious and cultural backgrounds.

PMID- 20044332
TI  - Caring for the caregiver.
AB  - PURPOSE/OBJECTIVES: To describe the quality of life (QOL) and well-being of
      caregivers of patients receiving outpatient chemotherapy for leukemia and to
      identify strategies to promote the best possible QOL and well-being for the
      caregivers. DESIGN: Descriptive, cross-sectional study. SETTING: Ambulatory
      treatment center of a major comprehensive cancer center in the southern United
      States. SAMPLE: Convenience sample of 194 caregivers of patients receiving
      chemotherapy for leukemia. METHODS: Participants completed the Caregiver Quality
      of-Life-Cancer Scale, the Caregiver Well-Being Scale, and the Learning Needs
      Questionnaire developed by the authors. Descriptive statistics were used to
      summarize the demographic characteristics of the caregivers, and exploratory
      factor analysis was performed to identify meaningful factors. MAIN RESEARCH
      VARIABLES: QOL, well-being, and learning needs. FINDINGS: Caregivers identified
      burden as their most important concern for QOL. Key factors identified with
      caregivers' well-being were expression of feelings and household maintenance.
      Caregivers identified giving medications and managing the side effects as crucial
      to learning needs. Communication, positive attitudes, support, and education were
      important in promoting QOL for the caregivers. CONCLUSIONS: Caregiving for a
      patient receiving chemotherapy for leukemia influences the QOL and well-being of
      the caregiver. IMPLICATIONS FOR NURSING: This study highlights the need for
      better nurse-caregiver communication and education, particularly in the areas of
      symptom management and medication administration. Additional research should
      focus on factors that affect caregivers' QOL, their educational needs, and
      improved interventions for delivering new information or reinforcing old
      information.

PMID- 20044333
TI  - Changes in sexual function on mood and quality of life in patients undergoing
      radiation therapy for prostate cancer.
AB  - PURPOSE/OBJECTIVES: To describe the percentages of men with and without changes
      in sexual function from the beginning to end of radiation therapy and evaluate
      for differences in demographic and clinical characteristics, mood states, and
      quality of life (QOL) among patients who did and did not experience changes in
      sexual function. DESIGN: Descriptive, longitudinal. SETTING: Two radiation
      therapy departments in northern California. SAMPLE: 70 men with prostate cancer
      who underwent primary or adjuvant radiation therapy. METHODS: Self-report
      questionnaires, medical record reviews, and repeated measures analysis of
      variance. MAIN RESEARCH VARIABLES: Changes in sexual function; depression,
      anxiety, and QOL. FINDINGS: Patients were categorized into one of four sex groups
      (No Problem X 2, Problem-No Problem, No Problem-Problem, and Problem X 2) based
      on their responses to "Is your sexuality impacted by your illness?" at the
      beginning and end of radiation therapy. About 50% had a problem with sexual
      function either at the beginning or end of radiation therapy. Overall, men
      without sexual problems at both the beginning and end of radiation therapy had
      significantly less anxiety and depression and higher QOL scores than patients who
      developed a problem at the end and patients who had a problem at both time
      points. CONCLUSIONS: Changes in sexual function during the course of radiation
      therapy affect patients' mood and QOL. IMPLICATIONS FOR NURSING: Clinicians
      should evaluate the effects of radiation therapy on sexual function and monitor
      patients with prostate cancer for depression and anxiety as well as for changes
      in QOL.

PMID- 20044334
TI  - Gender, symptom experience, and use of complementary and alternative medicine
      practices among cancer survivors in the U.S. cancer population.
AB  - PURPOSE/OBJECTIVES: To identify relationships among gender, physical and
      psychological symptoms (pain, insomnia, fatigue, and depression), and use of
      specific complementary and alternative medicine (CAM) practices among survivors
      in the U.S. cancer population. DESIGN: Secondary analysis of the 2002 National
      Health Interview Survey (NHIS). The CAM Healthcare Model, an extension of the
      Behavioral Model for Health Services Use, guided the study. SETTING: United
      States. SAMPLE: 2,262 adults (aged 18 years and older) diagnosed with cancer
      representing more than 14.3 million cancer survivors in the United States .
      METHODS: NHIS interview data on use of CAM practices (diet, yoga, tai chi,
      qigong, meditation, guided imagery, relaxation, and deep breathing) were examined
      in relationship to gender and symptoms. Analysis was conducted using Stata 9.2
      software for population estimation. Binary logistic regression, the primary
      statistical model employed in the analysis, focused on between-subject
      differences in practice use. MAIN RESEARCH VARIABLES: Dichotomous outcome
      variables included use of at least one CAM practice and use of specific
      individual CAM practices. Independent variables included gender, age, education,
      race, provider contact, cancer diagnosis, pain, insomnia, fatigue, depression,
      and health status. FINDINGS: CAM practice use was more prevalent among female,
      middle-aged, Caucasian, and well-educated subjects. Pain, depression, and
      insomnia were strong predictors of practice use, with differences noted by gender
      and practice type. CONCLUSIONS: CAM practices are widely used in the U.S. cancer
      population, especially among women. Symptom experience influences likelihood of
      use, with increased odds when men report symptoms. IMPLICATIONS FOR NURSING:
      Study findings inform oncology nurses on the benefits of integrating self-care
      CAM practices in relationship to gender into the symptom management care plan for
      cancer survivors. Findings reported in this study will help guide future CAM
      practice intervention studies.

PMID- 20044335
TI  - Making room at the table.

PMID- 20044337
TI  - Patient navigation: a "win-win" for all involved.

PMID- 20044338
TI  - Cervical cancer screening in young women: saving lives with prevention and
      detection.

PMID- 20044339
TI  - Pilots of oncology health care: a concept analysis of the patient navigator role.
AB  - PURPOSE/OBJECTIVES: To summarize the current scientific literature pertaining to
      the role of the patient navigator in oncology using the concept analysis
      framework developed by Walker and Avant. DATA SOURCES: Published research
      articles, clinical articles, and Internet sources on patient navigator roles and
      programs. Literature was obtained from CINAHL, PubMed, PsycINFO, the Cochrane
      Library, and Google Scholar, incorporating reports in English from 1990-2008.
      DATA SYNTHESIS: Patient navigation has received a plethora of attention as
      healthcare programs strive to streamline care and address current gaps in service
      delivery. The literature revealed that the role of the patient navigator remains
      context-specific and has been filled by a variety of individuals, including
      nurses, social workers, peer supporters, and lay individuals. CONCLUSIONS: The
      role of a patient navigator includes removing barriers to care, improving patient
      outcomes, and ameliorating the overall quality of healthcare delivery.
      IMPLICATIONS FOR NURSING: By examining the role of the patient navigator depicted
      in the scientific literature, nurses can gain insight into not only the features
      of navigation but also the current systematic gaps that call for navigation
      services. This article examines the numerous functions of a patient navigator and
      exemplifies the significance of the role in various domains.

PMID- 20044340
TI  - Implementing and measuring the impact of patient navigation at a comprehensive
      community cancer center.
AB  - PURPOSE/OBJECTIVES: To determine whether patient navigation in a comprehensive
      community cancer center affects patient and staff perceptions of patient
      preparation for treatment, access to care, and overall satisfaction. DESIGN:
      Program evaluation with patient and staff surveys. SETTING: Comprehensive
      community cancer center accredited by the American College of Surgeons in the
      southeastern United States with 1,037 analytic cases of cancer in 2007;
      population of the main county served is about 177,963. SAMPLE: 48 patients (28
      navigator and 20 non-navigator) and 26 employees, including physicians, nurses,
      and other support staff. METHODS: A 10-item survey with Likert scale format was
      sent to a stratified sample of 100 newly diagnosed patients with cancer. A five
      item survey with the same format was sent to 40 staff working with the patients.
      MAIN RESEARCH VARIABLE: Patient navigation. FINDINGS: Patients who received
      navigation services responded more positively to survey statements. Statistical
      significance (p > 0.05) was identified in 7 of 10 statements when patient groups
      were compared. Provider responses indicated agreement with all five statements
      included in the survey. CONCLUSIONS: Patients with cancer and oncology staff
      reported that patient navigation is effective in increasing patient satisfaction
      and decreasing barriers to care. IMPLICATIONS FOR NURSING: Patient navigation is
      an emerging trend in cancer care. Patient navigators can play a significant role
      in assisting patients with coordinating services across the continuum of care.
      Continued research is essential in refining the role and eminence of patient
      navigators.

PMID- 20044341
TI  - The role of the oncology nurse navigator in distress management of adult
      inpatients with cancer: a retrospective study.
AB  - PURPOSE/OBJECTIVES: To determine whether the oncology nurse navigator (ONN) role
      as an intervention decreases the distress of adult inpatients with cancer.
      DESIGN: Retrospective chart review was used to collect information about patient
      distress scores at admission and discharge. Scores were compared to determine
      whether the ONN role is effective in lowering patients' distress levels. SETTING:
      261-bed regional medical center in the midwestern United States. SAMPLE:
      Convenience sample of 55 inpatients with diagnoses of cancer. METHODS: Nurses
      asked patients with cancer to rate their distress daily during their stays.
      Correlation studies and two-tailed t tests were used to assess the relationship
      between the change in distress and the ONN intervention. MAIN RESEARCH VARIABLES:
      Distress scores of patients seen by the ONN versus distress scores of patients
      not seen by the ONN. FINDINGS: Patients seen by the ONN tended to have lower
      distress scores on dismissal (p = 0.1046). The difference was clinically
      significant to warrant providing an ONN for patient distress. ONN visits have a
      statistically significant effect on distress scores of inpatients 65 years of age
      or younger (p = 0.044) and those from rural settings (p = 0.045). CONCLUSIONS: An
      ONN can lower patients' cancer-related distress scores. Other research has shown
      that ONNs can help increase patient satisfaction; this research shows that the
      satisfaction may be related to a decrease in distress and increase in overall
      quality of life. IMPLICATIONS FOR NURSING: Patients experience high distress
      levels that can interfere with treatment compliance. This research shows that
      patients benefit from having an ONN to answer their questions and provide them
      with education about their diseases.

PMID- 20044342
TI  - Uncertainty during breast diagnostic evaluation: state of the science.
AB  - PURPOSE/OBJECTIVES: To present the state of the science on uncertainty in
      relationship to the experiences of women undergoing diagnostic evaluation for
      suspected breast cancer. DATA SOURCES: Published articles from Medline, CINAHL,
      PubMED, and PsycINFO from 1983-2008 using the following key words: breast biopsy,
      mammography, uncertainty, reframing, inner strength, and disruption. DATA
      SYNTHESIS: Fifty research studies were examined with all reporting the presence
      of anxiety persisting throughout the diagnostic evaluation until certitude is
      achieved through the establishment of a definitive diagnosis. Indirect
      determinants of uncertainty for women undergoing breast diagnostic evaluation
      include measures of anxiety, depression, social support, emotional responses,
      defense mechanisms, and the psychological impact of events. CONCLUSIONS:
      Understanding and influencing the uncertainty experience have been suggested to
      be key in relieving psychosocial distress and positively influencing future
      screening behaviors. Several studies examine correlational relationships among
      anxiety, selection of coping methods, and demographic factors that influence
      uncertainty. A gap exists in the literature with regard to the relationship of
      inner strength and uncertainty. IMPLICATIONS FOR NURSING: Nurses can be
      invaluable in assisting women in coping with the uncertainty experience by
      providing positive communication and support. Nursing interventions should be
      designed and tested for their effects on uncertainty experienced by women
      undergoing a breast diagnostic evaluation.

PMID- 20044343
TI  - Patient perceptions of arm care and exercise advice after breast cancer surgery.
AB  - PURPOSE/OBJECTIVES: To describe in greater detail women's experiences receiving
      advice about arm care and exercise after breast cancer treatment. DESIGN: Cross
      sectional survey. SETTING: Three hospitals in Sydney, Australia. SAMPLE: 175
      patients with breast cancer recruited 6-15 months after their surgery. METHODS:
      Patients completed a survey about their perceptions of arm activity after breast
      cancer and were asked to respond to an open-ended question about their experience
      receiving advice about arm care and exercise. Comments from 48 women (27%) who
      volunteered responses were collated and categorized. MAIN RESEARCH VARIABLES:
      Patients' experience with arm care and exercise advice after breast cancer
      surgery. FINDINGS: Topics raised by respondents included perceptions of
      inadequate and conflicting advice, lack of acknowledgment of women's concerns
      about upper limb impairments, an unsupported search for information about upper
      limb impairments, fear of lymphedema, women's demand for follow-up physiotherapy,
      and some positive experiences with supportive care. CONCLUSIONS: Upper limb
      impairments are problematic for some breast cancer survivors, and these concerns
      are not always taken seriously by health professionals. To date, standardized
      advice is provided that does not meet the needs and expectations of a cohort of
      women after breast cancer surgery. IMPLICATIONS FOR NURSING: Health professionals
      could better address patients' concerns about upper limb impairments by providing
      accurate advice relevant to the surgery.

PMID- 20044344
TI  - Quality of life, social support, and uncertainty among Latina and Caucasian
      breast cancer survivors: a comparative study.
AB  - PURPOSE/OBJECTIVES: To examine the differences between Latina and Caucasian
      breast cancer survivors in perceived social support, uncertainty, and quality of
      life (QOL), and the differences between the cohorts in selected demographic
      variables. DESIGN: Descriptive, comparative study. SETTING: Selected private
      hospitals and American Cancer Society units in a metropolitan area of the
      northeastern United States. SAMPLE: 182 Caucasian and 98 Latina breast cancer
      survivors. METHODS: Participants completed a personal data sheet, the Social
      Support Questionnaire, the Mishel Uncertainty in Illness Scale-Community Form,
      and the Ferrans and Powers QOL Index-Cancer Version III at home and returned the
      questionnaires to the investigators via postage-paid envelope. MAIN RESEARCH
      VARIABLES: Perceived social support, uncertainty, and QOL. FINDINGS: Caucasians
      reported significantly higher levels of total perceived social support and QOL
      than Latinas. CONCLUSIONS: Psychiatric illness comorbidity and lower level of
      education in Latinas were factors in the disparity of QOL. IMPLICATIONS FOR
      NURSING: Nurses should be mindful of the essential association of perceived
      social support, uncertainty, and QOL in Latina breast cancer survivors and how
      Latinas differ from Caucasian breast cancer survivors. Factors such as cultural
      values, comorbidities, and education level likely influence perceived social
      support, uncertainty, and QOL.

PMID- 20044347
TI  - Caught in the act: the lifetime of synaptic intermediates during the search for
      homology on DNA.
AB  - Homologous recombination plays pivotal roles in DNA repair and in the generation
      of genetic diversity. To locate homologous target sequences at which strand
      exchange can occur within a timescale that a cell's biology demands, a single
      stranded DNA-recombinase complex must search among a large number of sequences on
      a genome by forming synapses with chromosomal segments of DNA. A key element in
      the search is the time it takes for the two sequences of DNA to be compared, i.e.
      the synapse lifetime. Here, we visualize for the first time fluorescently tagged
      individual synapses formed by RecA, a prokaryotic recombinase, and measure their
      lifetime as a function of synapse length and differences in sequence between the
      participating DNAs. Surprisingly, lifetimes can be approximately 10 s long when
      the DNAs are fully heterologous, and much longer for partial homology,
      consistently with ensemble FRET measurements. Synapse lifetime increases rapidly
      as the length of a region of full homology at either the 3'- or 5'-ends of the
      invading single-stranded DNA increases above 30 bases. A few mismatches can
      reduce dramatically the lifetime of synapses formed with nearly homologous DNAs.
      These results suggest the need for facilitated homology search mechanisms to
      locate homology successfully within the timescales observed in vivo.

PMID- 20044348
TI  - Control of directionality in the DNA strand-exchange reaction catalysed by the
      tyrosine recombinase TnpI.
AB  - In DNA site-specific recombination catalysed by tyrosine recombinases, two pairs
      of DNA strands are sequentially exchanged between separate duplexes and the
      mechanisms that confer directionality to this theoretically reversible reaction
      remain unclear. The tyrosine recombinase TnpI acts at the internal resolution
      site (IRS) of the transposon Tn4430 to resolve intermolecular transposition
      products. Recombination is catalysed at the IRS core sites (IR1-IR2) and is
      regulated by adjacent TnpI-binding motifs (DR1 and DR2). These are dispensable
      accessory sequences that confer resolution selectivity to the reaction by
      stimulating synapsis between directly repeated IRSs. Here, we show that formation
      of the DR1-DR2-containing synapse imposes a specific order of activation of the
      TnpI catalytic subunits in the complex so that the IR1-bound subunits catalyse
      the first strand exchange and the IR2-bound subunits the second strand exchange.
      This ordered pathway was demonstrated for a complete recombination reaction using
      a TnpI catalytic mutant (TnpI-H234L) partially defective in DNA rejoining. The
      presence of the DR1- and DR2-bound TnpI subunits was also found to stabilize
      transient recombination intermediates, further displacing the reaction
      equilibrium towards product formation. Implication of TnpI/IRS accessory elements
      in the initial architecture of the synapse and subsequent conformational changes
      taking place during strand exchange is discussed.

PMID- 20044350
TI  - RepD-mediated recruitment of PcrA helicase at the Staphylococcus aureus pC221
      plasmid replication origin, oriD.
AB  - Plasmid encoded replication initiation (Rep) proteins recruit host helicases to
      plasmid replication origins. Previously, we showed that RepD recruits
      directionally the PcrA helicase to the pC221 oriD, remains associated with it,
      and increases its processivity during plasmid unwinding. Here we show that RepD
      forms a complex extending upstream and downstream of the core oriD. Binding of
      RepD causes remodelling of a region upstream from the core oriD forming a
      'landing pad' for the PcrA. PcrA is recruited by this extended RepD-DNA complex
      via an interaction with RepD at this upstream site. PcrA appears to have weak
      affinity for this region even in the absence of RepD. Upon binding of ADPNP (non
      hydrolysable analogue of ATP), by PcrA, a conformational rearrangement of the
      RepD-PcrA-ATP initiation complex confines it strictly within the boundaries of
      the core oriD. We conclude that RepD-mediated recruitment of PcrA at oriD is a
      three step process. First, an extended RepD-oriD complex includes a region
      upstream from the core oriD; second, the PcrA is recruited to this upstream
      region and thirdly upon ATP-binding PcrA relocates within the core oriD.

PMID- 20044349
TI  - Molecular mechanisms of eukaryotic pre-mRNA 3' end processing regulation.
AB  - Messenger RNA (mRNA) 3' end formation is a nuclear process through which all
      eukaryotic primary transcripts are endonucleolytically cleaved and most of them
      acquire a poly(A) tail. This process, which consists in the recognition of
      defined poly(A) signals of the pre-mRNAs by a large cleavage/polyadenylation
      machinery, plays a critical role in gene expression. Indeed, the poly(A) tail of
      a mature mRNA is essential for its functions, including stability, translocation
      to the cytoplasm and translation. In addition, this process serves as a bridge in
      the network connecting the different transcription, capping, splicing and export
      machineries. It also participates in the quantitative and qualitative regulation
      of gene expression in a variety of biological processes through the selection of
      single or alternative poly(A) signals in transcription units. A large number of
      protein factors associates with this machinery to regulate the efficiency and
      specificity of this process and to mediate its interaction with other nuclear
      events. Here, we review the eukaryotic 3' end processing machineries as well as
      the comprehensive set of regulatory factors and discuss the different molecular
      mechanisms of 3' end processing regulation by proposing several overlapping
      models of regulation.

PMID- 20044351
TI  - Alternative splicing of Tcf7l2 transcripts generates protein variants with
      differential promoter-binding and transcriptional activation properties at
      Wnt/beta-catenin targets.
AB  - Alternative splicing can produce multiple protein products with variable domain
      composition from a single gene. The mouse Tcf7l2 gene is subject to alternative
      splicing. It encodes TCF4, a member of the T-cell factor (TCF) family of DNA
      binding proteins and a nuclear interaction partner of beta-catenin which performs
      essential functions in Wnt growth factor signalling. Multiple TCF4 isoforms,
      potentially exhibiting cell-type-specific distribution and differing in gene
      regulatory properties, could strongly influence tissue-specific Wnt responses.
      Therefore, we have examined mouse Tcf7l2 splice variants in neonatal tissues,
      embryonic stem cells and neural progenitors. By polymerase chain reaction
      amplification, cloning and sequencing, we identify a large number of
      alternatively spliced transcripts and report a highly flexible combinatorial
      repertoire of alternative exons. Many, but not all of the variants exhibit a
      broad tissue distribution. Moreover, two functionally equivalent versions of the
      C-clamp, thought to represent an auxiliary DNA-binding domain, were identified.
      Depending upon promoter context and precise domain composition, TCF4 isoforms
      exhibit strikingly different transactivation potentials at natural Wnt/beta
      catenin target promoters. However, differences in C-clamp-mediated DNA binding
      can only partially explain functional differences among TCF4 variants. Still, the
      cell-type-specific complement of TCF4 isoforms is likely to be a major
      determinant for the context-dependent transcriptional output of Wnt/beta-catenin
      signalling.

PMID- 20044352
TI  - Computing folding pathways between RNA secondary structures.
AB  - Given an RNA sequence and two designated secondary structures A, B, we describe a
      new algorithm that computes a nearly optimal folding pathway from A to B. The
      algorithm, RNAtabupath, employs a tabu semi-greedy heuristic, known to be an
      effective search strategy in combinatorial optimization. Folding pathways,
      sometimes called routes or trajectories, are computed by RNAtabupath in a
      fraction of the time required by the barriers program of Vienna RNA Package. We
      benchmark RNAtabupath with other algorithms to compute low energy folding
      pathways between experimentally known structures of several conformational
      switches. The RNApathfinder web server, source code for algorithms to compute and
      analyze pathways and supplementary data are available at
      http://bioinformatics.bc.edu/clotelab/RNApathfinder.

PMID- 20044353
TI  - A novel motif in telomerase reverse transcriptase regulates telomere repeat
      addition rate and processivity.
AB  - Telomerase is a specialized reverse transcriptase that adds telomeric DNA repeats
      onto chromosome termini. Here, we characterize a new telomerase-specific motif,
      called motif 3, in the catalytic domain of telomerase reverse transcriptase, that
      is crucial for telomerase function and evolutionally conserved between
      vertebrates and ciliates. Comprehensive mutagenesis of motif 3 identified
      mutations that remarkably increase the rate or alter the processivity of telomere
      repeat addition. Notably, the rate and processivity of repeat addition are
      affected independently by separate motif 3 mutations. The processive telomerase
      action relies upon a template translocation mechanism whereby the RNA template
      and the telomeric DNA strand separate and realign between each repeat synthesis.
      By analyzing the mutant telomerases reconstituted in vitro and in cells, we show
      that the hyperactive mutants exhibit higher repeat addition rates and faster
      enzyme turnovers, suggesting higher rates of strand-separation during template
      translocation. In addition, the strong correlation between the processivity of
      the motif 3 mutants and their ability to use an 8 nt DNA primer, suggests that
      motif 3 facilitates realignment between the telomeric DNA and the template RNA
      following strand-separation. These findings support motif 3 as a key determinant
      for telomerase activity and processivity.

PMID- 20044354
TI  - FDA launches plan to prevent unnecessary harm from medication use.

PMID- 20044358
TI  - Use of defined-daily-doses per 100 bed-days for measuring consumption of
      antiinfectives in a pediatric hospital.

PMID- 20044359
TI  - Effect of an educational initiative on physicians' use of weight-based
      fosphenytoin loading doses in the emergency department.

PMID- 20044360
TI  - Availability and characteristics of teaching certificates offered by pharmacy
      residency programs.

PMID- 20044361
TI  - Effects of requiring a baseline International Normalized Ratio for inpatients
      treated with warfarin.

PMID- 20044362
TI  - Developing models for pharmacy practice.

PMID- 20044363
TI  - Medication administration through feeding tubes.

PMID- 20044365
TI  - Health care workers and influenza vaccination.

PMID- 20044366
TI  - Converting from brand-name to generic clozapine: a review of effectiveness and
      tolerability data.
AB  - PURPOSE: The effectiveness and tolerability of switching patients' therapy from
      brand-name to generic clozapine are reviewed. SUMMARY: Clozapine is the most
      effective treatment for patients with refractory psychotic disorders and is also
      effective for reducing suicidal and violent behavior in this same population.
      Generic versions of clozapine are widely used. However, possible differences in
      pharmacokinetic profiles between branded and generic clozapine, and the potential
      risks of medication changes in severely ill but stable patients, may result in
      apprehension about converting from branded to generic clozapine. Articles,
      abstracts, and clinical presentations that compared clinical outcomes between
      Clozaril (Novartis Pharmaceuticals, East Hanover, NJ) and generic forms of
      clozapine in patients with primary psychotic disorders, bipolar disorder, or
      related conditions were identified via a computerized search of the medical
      literature. Thirteen relevant reports, mostly uncontrolled observational studies
      or chart reviews, described the effects of switching from brand-name to generic
      clozapine in 966 patients. The majority of patients tolerated conversion without
      worsening of symptoms or adverse effects, increased intensive service
      utilization, or medication adjustment. Clinical deterioration was described in a
      case review and in one randomized, controlled study. CONCLUSION: Available
      literature supports the effectiveness and safety of generic clozapine
      formulations in patients who previously were stable during treatment with brand
      name clozapine. The risk of poor outcome after conversion to a generic clozapine
      formulation appears to be low but difficult to predict. Patients should be
      closely monitored during the first one to three months after conversion from one
      formulation to another.

PMID- 20044367
TI  - Elevated International Normalized Ratio associated with concurrent use of
      ophthalmic erythromycin and warfarin.
AB  - PURPOSE: The case of a patient whose International Normalized Ratio (INR)
      increased with concurrent use of ophthalmic erythromycin and warfarin is
      reported. SUMMARY: A 77-year-old Caucasian woman began therapy with warfarin for
      thromboembolism prophylaxis secondary to atrial fibrillation (target INR, 2-3).
      Warfarin was prescribed by her cardiologist, and care was established with
      clinical pharmacists in an anticoagulation clinic. She was receiving a weekly
      maintenance dosage of 14 mg. She had a history of atrial fibrillation,
      hyperlipidemia, osteoarthritis, hypothyroidism, coronary artery disease,
      myocardial infarction, congestive heart failure, and breast cancer. In addition
      to warfarin, the patient had been receiving alprazolam, carvedilol, furosemide,
      levothyroxine sodium, lisinopril, nitroglycerin, potassium chloride, propoxyphene
      hydrochloride-acetaminophen, simvastatin, and trazodone. After receiving warfarin
      at the same weekly dosage for over four months, the patient's ophthalmologist
      prescribed erythromycin ophthalmic ointment for chronic bacterial conjunctivitis.
      Three weeks later, her INR was found to be 8.5. A total of four warfarin doses
      were withheld, and her weekly maintenance dosage of warfarin was subsequently
      decreased to 12 mg. Five weeks later, her INR was 1.5, and it was determined that
      the erythromycin ophthalmic ointment had been discontinued five days prior. Her
      weekly maintenance dosage of warfarin was increased to 16 mg. Rechallenge with
      erythromycin five days before her next INR measurement resulted in an INR of 4.2.
      A new weekly maintenance dosage of 13 mg was established, and her subsequent INRs
      were within normal range. CONCLUSION: An increase in INR values was reported
      after initiation of ophthalmic erythromycin in a patient receiving warfarin and
      recurred upon rechallenge with ophthalmic erythromycin.

PMID- 20044368
TI  - Collaborative drug therapy management for initiating and adjusting insulin
      therapy in patients with type 2 diabetes mellitus.
AB  - PURPOSE: Collaborative drug therapy management (CDTM) by pharmacists for
      initiating and adjusting insulin therapy in patients with type 2 diabetes
      mellitus in a Veterans Affairs Health Care System (VAHCS) is described. SUMMARY:
      During 2003-04, the Veterans Affairs Maryland Health Care System (VAMHCS) at
      Baltimore reported that 24% of its patients with diabetes had a glycosylated
      hemoglobin (HbA(1c)) value of >9% or no recently documented HbA(1c) and that 91%
      of its patients with an HbA(1c) value of >9% were treated with oral
      antihyperglycemic agents alone. To address this issue, clinical pharmacists at
      VAMHCS at Baltimore developed the insulin initiation clinic. The primary goal of
      VAMHCS at Baltimore insulin initiation clinic was to provide an appropriate
      infrastructure to address the needs of patients with poorly controlled type 2
      diabetes who required insulin therapy. Patients could be referred to the clinic
      if they had an HbA(1c) value of >9% on two occasions at least three months apart
      and were taking two oral antidiabetic medications whose dose was at least 50% of
      the maximal dose. The participating pharmacists mutually agreed to follow an
      insulin dosing protocol to help guide their therapeutic decision-making. Patients
      received comprehensive education during the initial visit regarding self
      management skills, self-monitoring of blood glucose levels, treatment of
      hypoglycemia, insulin injection administration, and lifestyle modifications.
      Patients were discharged to their primary care provider if they attained an
      HbA(1c) value of <7.5% or after six months, whichever came first, during January
      2005 and July 2008. CONCLUSION: Use of a preplanned insulin initiation and
      titration protocol by pharmacists resulted in the successful implementation of an
      insulin initiation clinic through CDTM and improved patients' glycemic control.

PMID- 20044369
TI  - Origins of and solutions for neonatal medication-dispensing errors.
AB  - PURPOSE: Five cases of sound-alike, look-alike, neonatal medication-dispensing
      errors and their resolution are reviewed. SUMMARY: In 2008, there were five cases
      in which look-alike or sound-alike neonatal medication-dispensing errors occurred
      at our institution. A mix-up between neonatal and adult or pediatric products
      occurred in four of the five cases. Three of the five errors resulted in near
      misses with the potential to cause harm. The other two errors reached the
      patients but did not cause harm. The medication mix-ups involved adult and
      neonatal phytonadione injectable emulsion, sodium citrate injection and
      vancomycin-heparin combination injection, adult tetanus-diphtheria-acellular
      pertussis and infant diphtheria-tetanus-acellular pertussis (DTaP) vaccines,
      Haemophilus B and DTaP vaccines, and cisatracurium and vecuronium. Each error
      exposed weaknesses in the system of neonatal medication storage, labeling,
      delivery, knowledge, and administration documentation at our institution.
      Resolution of system problems was made possible by a collaborative approach and
      involved reorganizing shelving used to store neonatal medications; using a
      differently colored labeling scheme for products whose syringes were nearly
      identical; implementing changes to the infant vaccine ordering, storage,
      dispensing, and documentation systems; and instituting centralized and
      decentralized pharmacist review of pharmacy technician automated dispensing
      cabinet-filling activities. CONCLUSION: An institution providing services to both
      neonatal and adult patients experienced five cases of medication-dispensing
      errors with look-alike or sound-alike medications. Multidisciplinary
      collaboration within the system helped the pharmacy identify, resolve, and
      prevent errors related to medication storage, labeling, delivery, knowledge, and
      administration documentation.

PMID- 20044370
TI  - Implementation and evaluation of a comprehensive system to deliver pediatric
      continuous infusion medications with standardized concentrations.
AB  - PURPOSE: The development, implementation, and evaluation of a comprehensive
      pediatric medication management system based on computerized orders with
      standardized concentrations for pediatric continuous infusions are described.
      SUMMARY: To attain the Joint Commission mandate of using a few standardized
      concentrations for pediatric continuous infusion medications, a multidisciplinary
      team at the University of Maryland Medical Center pediatric intensive care unit
      restructured the medication management of continuous infusions from the
      handwritten rule-of-6 method to computerized orders with standardized
      concentrations. Development of the new system required creating a mathematical
      algorithm to automatically produce two to four standardized concentrations for 39
      continuous infusion medications used in pediatrics, incorporating mnemonics that
      represent standard drug concentrations into the pharmacy medication-processing
      system, designing a computerized provider-order-entry program, and introducing
      smart infusion pumps that were programmed with standardized concentrations.
      System creation and implementation were completed hospitalwide over 16 months.
      The system successfully determined two to four standardized concentrations for
      each continuous infusion medication and allowed application of consistent dose,
      weight, and fluid restrictions when determining standardized concentrations.
      Preimplementation and postimplementation evaluation revealed that the new system
      eliminated several types of medication errors and was well received by all health
      care team members in pediatrics units. CONCLUSION: A technology-based,
      scientific, comprehensive yet simplified solution to attain the Joint Commission
      mandate concerning standardized concentrations was developed, implemented, and
      evaluated. The system successfully determined a limited number of concentrations
      for each continuous infusion medication for pediatrics and improved safety by
      eliminating medication errors when delivering these medications.

PMID- 20044371
TI  - Implementation and evaluation of vancomycin nomogram guidelines in a computerized
      prescriber-order-entry system.
AB  - PURPOSE: The implementation and evaluation of vancomycin nomogram guidelines in a
      computerized prescriber-order-entry (CPOE) system are described. METHODS: Initial
      vancomycin orders for patients over age 18 years who received vancomycin between
      August 1 and September 30, 2006 (preimplementation), and between March 1 and
      April 30, 2007 (postimplementation), were compared with vancomycin nomogram
      recommendations to determine if the vancomycin regimen ordered coincided with the
      nomogram recommendation. The numbers of regimen changes and vancomycin serum
      concentrations measured during the first five days of therapy were also assessed.
      A multivariate logistic regression model assessed independent predictors of an
      initial vancomycin order that met the nomogram recommendation RESULTS: A total of
      522 vancomycin orders were included in the analysis (279 in the preimplementation
      group and 243 in the postimplementation group). A significant difference was
      observed in the percentage of initial vancomycin orders that met nomogram
      recommendations in the postimplementation group compared with the
      preimplementation group (36% versus 24%, p = 0.0028). No difference was noted
      between the two groups in the number of regimen changes or serum vancomycin
      concentrations measured during the first five days of therapy. In a multivariate
      analysis, age (p = 0.02) and weight (p < 0.0001) were negatively associated with
      a vancomycin order that met nomogram recommendations, while the
      postimplementation group was positively associated with an order that met
      nomogram recommendations (p = 0.001). CONCLUSION: A vancomycin nomogram
      implemented into a CPOE system increased the likelihood of patients receiving an
      initial vancomycin regimen that coincided with the nomogram's recommendations.

PMID- 20044375
TI  - An important recent development in cancer research has been the identification of
      new genetic and molecular tumor profiling techniques. Introduction.

PMID- 20044377
TI  - Histological and genetic markers for non-small-cell lung cancer: customizing
      treatment based on individual tumor biology.
AB  - PURPOSE: To describe how molecular and genetic markers influence the response to
      therapy in patients with advanced non-small-cell lung cancer (NSCLC). SUMMARY:
      Cisplatin resistance has been associated with high rates of expression of
      endonucleases, a family of DNA repair proteins that includes ERCC1 and BRCA1.
      Gemcitabine is thought to produce its antitumor effects by several mechanisms,
      including inhibition of ribonucleotide conversion to deoxyribonucleotide through
      the inactivation of ribonucleotide reductase. One type of gemcitabine resistance
      occurs when the inactivation of ribonucleotide reductase decreases, which
      correlates with increased expression of the M1 subunit of ribonucleotide
      reductase. Taxanes produce their anti-tumor effects by binding to and stabilizing
      intracellular microtubules, which are necessary for DNA replication and cell
      division. High expression of beta-tubulin III, a microtubule subunit with low
      taxane binding affinity, appears to confer resistance to taxane therapy. High
      expression of thymidylate synthase, an enzyme that is important in purine
      synthesis and DNA replication, has been associated with decreased response to
      uracil antimetabolites, and may also be an important prognostic factor in
      patients receiving pemetrexed. The epidermal growth factor receptor (EGFR) is a
      cell- surface receptor with an intracellular tyrosine kinase domain that is
      thought to modulate numerous cellular functions that contribute to
      tumorigenicity, tumor invasiveness, and resistance to therapy. Recent clinical
      trials have demonstrated that treatment response to small-molecule and monoclonal
      antibody inhibitors of EGFR is greatest for patients who have a higher EGFR gene
      copy number. CONCLUSION: Several genetic, molecular, and histological markers may
      affect treatment response in patients with NSCLC. Evaluating patients for such
      markers is important not only for treatment efficacy, but also to improve safety
      and tolerability by avoiding exposure to treatments that are unlikely to produce
      significant benefits. Nearly all of the available information regarding the
      predictive value of these markers has been derived from retrospective studies.
      Prospective clinical trials are important to validate marker evaluation
      methodology and the prospective utility of biomarkers in clinical decision
      making.

PMID- 20044378
TI  - Current and emerging therapies for patients with advanced non-small-cell lung
      cancer.
AB  - PURPOSE: To review recent clinical trials that have examined new options for the
      treatment of non-small-cell lung cancer (NSCLC) and to review the importance of
      tumor histology and genetics in the selection of therapy. SUMMARY: Targeted
      biological agents have been evaluated for use in patients with NSCLC. In a recent
      study, treatment with cetuximab plus chemotherapy led to significant improvement
      in overall survival (OS) in patients with advanced NSCLC. A Phase III,
      noninferiority, randomized study evaluating first-line therapy in patients with
      stage IIIb or IV NSCLC demonstrated that the combination of cisplatin and
      pemetrexed was noninferior to cisplatin and gemcitabine in improving OS and other
      clinical outcomes. In this study, the combination of pemetrexed and cisplatin was
      effective in patients with nonsquamous disease, whereas the combination of
      cisplatin and gemcitabine was effective in improving progression-free survival
      (PFS) in patients with squamous cell carcinoma. Clinical trials of maintenance
      therapy presented at the 2009 annual meeting of the American Society of Clinical
      Oncology reported significant benefit of pemetrexed in patients with nonsquamous
      tumor histology, and of erlotinib in patients with squamous and nonsquamous
      histology. For second-line therapy, studies of the investigational tyrosine
      kinase inhibitor, vandetanib, failed to demonstrate improved OS with vandetanib
      in combination with docetaxel or pemetrexed, or in direct comparison with
      erlotinib. In another study, the addition of bevacizumab to erlotinib for second
      line treatment of NSCLC did not result in greater OS than erlotinib alone.
      CONCLUSION: New treatment strategies are needed to improve clinical outcomes for
      patients with advanced NSCLC. The introduction of new agents with improved
      tolerability profiles has led to interest in long-term maintenance therapy in
      this patient population. Clinical trials suggest that tumor histology and
      genetics should be considered when selecting treatments for these patients.

PMID- 20044379
TI  - Fitting general relative risk models for survival time and matched case-control
      analysis.
AB  - Cox proportional hazards regression analysis of survival data and conditional
      logistic regression analysis of matched case-control data are methods that are
      widely used by epidemiologists. Standard statistical software packages
      accommodate only log-linear model forms, which imply exponential exposure
      response functions and multiplicative interactions. In this paper, the authors
      describe methods for fitting non-log-linear Cox and conditional logistic
      regression models. The authors use data from a study of lung cancer mortality
      among Colorado Plateau uranium miners (1950-1982) to illustrate these methods for
      fitting general relative risk models to matched case-control control data,
      countermatched data with weights, d:m matching, and full cohort Cox regression
      using the SAS statistical package (SAS Institute Inc., Cary, North Carolina).

PMID- 20044390
TI  - A case of anaplastic carcinoma of the pancreas with portal vein tumor thrombus.

PMID- 20044391
TI  - Comparison of time trends in uterus cancer and cervix uteri cancer mortality
      (1990-2006) in the world, from the WHO Mortality Database.

PMID- 20044393
TI  - Too early to declare H1N1 swine flu pandemic over, says WHO chief.

PMID- 20044394
TI  - A/H1N1 flu pandemic. Fever as nature's engine?

PMID- 20044395
TI  - Reduced level of consciousness from baclofen in people with low kidney function.

PMID- 20044396
TI  - Progest-erone, ogen, in? Which is it?

PMID- 20044397
TI  - Diagnosis of diabetes. First define impaired fasting glycaemia.

PMID- 20044398
TI  - Diagnosis of diabetes. What about cystic fibrosis?

PMID- 20044399
TI  - Diagnosis of diabetes. Consider life span of red cells.

PMID- 20044400
TI  - Diagnosis of diabetes. Haemoglobin A1c: ethnic differences apply to the UK.

PMID- 20044401
TI  - Hypercalcaemia. Two myths.

PMID- 20044402
TI  - Smoking status and pregnancy. Utility of point of care cotinine test during
      pregnancy.

PMID- 20044403
TI  - Varenicline and suicide. Safety data from New Zealand.

PMID- 20044404
TI  - Drug firm conflicting interests. If only industry funded trials were as well done
      as the WHI.

PMID- 20044406
TI  - Drug firm conflicting interests. Quis custodiet ipsos custodes?

PMID- 20044405
TI  - Drug firm conflicting interests. Radical change, not tweaking, is needed.

PMID- 20044409
TI  - Referral for medical evaluation: an ethical obligation?

PMID- 20044410
TI  - Law & psychiatry: Liability issues associated with referrals to self-help groups.
AB  - Self-help groups, which are also referred to as mutual aid groups, are widely
      recognized as an important component of a comprehensive public mental health
      system that promotes recovery. Nonetheless, some psychiatrists and other
      providers have expressed concerns about these consumer-run groups and fear
      potential liability if they make referrals and something harmful occurs. This
      column reviews potential liability claims that could be made pertaining to
      referrals to self-help groups. The authors conclude that the likelihood of
      success of a plaintiff's claim is small. Recommendations are given for further
      lowering the likelihood of a successful suit.

PMID- 20044411
TI  - Datapoints: depot antipsychotic use in New York State hospitals, 1994 to 2009.

PMID- 20044412
TI  - Antidepressants and suicide risk: how did specific information in FDA safety
      warnings affect treatment patterns?
AB  - OBJECTIVE: From June 2003 through October 2004, the U.S. Food and Drug
      Administration (FDA) released five safety warnings related to antidepressant use
      and the increased risk of suicidality for children. Although researchers have
      documented a decline in antidepressant use among children over this period, less
      is known about whether specific safety information conveyed in individual
      warnings was reflected in treatment patterns. METHODS: Thomson Reuters MarketScan
      claims data (2001-2005) for a national sample of privately insured children were
      used to construct treatment episodes (N=22,689). For each new episode of major
      depressive disorder, it was determined whether treatment followed specific
      recommendations included in warnings released by the FDA. Treatment
      recommendations pertained to the use of the antidepressants paroxetine and
      fluoxetine and to patient monitoring. Treatment patterns were expected to change
      as the risk information conveyed by the FDA changed over time. RESULTS: The
      timing of FDA recommendations was associated with trends in the use of paroxetine
      and fluoxetine by children with major depressive disorder who were initiating
      antidepressant treatment. However, no evidence of increases in outpatient visits
      (indicative of monitoring) among depressed children initiating antidepressant use
      was found. CONCLUSIONS: Release of specific risk and benefit information by the
      FDA was associated with changes in prescribing but not in outpatient follow-up.
      These results suggest that the FDA plays an important role in communicating
      information to the public and providers. Yet, although public health safety
      warnings were associated with changes in some practice patterns, not all
      recommendations conveyed in warnings were followed.

PMID- 20044413
TI  - Mental health service use among suicidal adolescents: findings from a U.S.
      national community survey.
AB  - OBJECTIVE: This study assessed patterns of mental health service use among
      adolescents who had attempted suicide and examined factors associated with their
      service use at individual, family, and community levels. METHODS: Bivariate and
      multiple logistic regression analyses were conducted with data from 877
      adolescents aged 12-17 who had attempted suicide in the past 12 months and who
      participated in the 2000 National Household Survey on Drug Abuse. RESULTS: Of the
      877 adolescents, less than half (45%) reported that they had used mental health
      services in the past 12 months. Adolescents from racial-ethnic minority groups
      were less likely than whites to receive inpatient or outpatient mental health
      treatment, even when the analyses controlled for other demographic, individual,
      and family and community characteristics. Poor self-perceived health and living
      in a single-parent family were associated with use of inpatient services. Female
      gender, higher family income, participation in extracurricular activities, and
      the presence of symptoms of anxiety or disruptive disorders were associated with
      use of outpatient services. Use of school-based mental health services was
      associated only with participation in extracurricular activities. CONCLUSIONS:
      The mental health service needs of suicidal adolescents, especially those from
      ethnic minority groups and lower-income families, too frequently remain unmet.
      Larger racial-ethnic disparities were found in use of inpatient and outpatient
      mental health services than in use of school-based services. Mental health
      services offered within school settings can reach suicidal adolescents who need
      services but may experience barriers to standard types of care.

PMID- 20044414
TI  - Suicide risk and acute psychiatric readmissions: a prospective cohort study.
AB  - OBJECTIVE: The objective was to improve knowledge of the role and functioning of
      psychiatric acute wards with respect to admissions because of suicide risk and
      factors associated with readmission. METHODS: Over one year, 1,245 consecutive
      psychiatric patients from a Norwegian catchment area were included at index
      admission and reassessed in cases of readmission. After a mean follow-up period
      of 562 days, a total of 1,234 readmissions were assessed. Time from discharge to
      readmission was analyzed with univariate and multivariate Cox regression
      analyses. Outcome variables included acute readmissions and readmissions for
      suicide risk. RESULTS: Fifty-four percent of the index admissions and 62% of the
      readmissions were related to suicide risk. Substance use disorders, personality
      disorders, prior psychiatric hospitalization, unemployment, and receipt of social
      benefits were significant predictors of any readmissions and readmissions because
      of suicide risk. At index admission suicidal ideation or suicide plans
      significantly predicted readmission because of suicide risk. A small subgroup of
      patients contributed disproportionately to the number of readmissions. A higher
      number of readmissions per individual patient was associated with greater
      tendency of admission because of suicide risk. CONCLUSIONS: The acute ward played
      an important role for patients with suicidal behavior. Care providers and
      clinicians should focus on staff training and supervision with regard to
      assessment and management of suicidal patients. Collaboration with referring
      physicians and aftercare providers is also important to help patients gain
      constructive coping strategies and break patterns of suicidal behavior and
      readmission.

PMID- 20044415
TI  - Assessment of physical illness by mental health clinicians during intake visits.
AB  - OBJECTIVES: This study explored how mental health clinicians assess and respond
      to physical illness among patients presenting for mental health intake
      evaluations. METHODS: A total of 129 adults were seen for a mental health intake
      visit. The intake visits were videotaped and involved 47 mental health clinicians
      from eight clinics who provided outpatient mental health and substance abuse
      treatment. A total of 120 videos of patient-provider interactions were coded
      using an information checklist containing 21 physical illness items. Twenty-eight
      intake visits exemplifying in-depth physical illness assessments were selected
      and transcribed for qualitative analysis. RESULTS: Physical health was discussed
      in most intake visits (87%). Clinicians elicited information on physical health
      in 79 visits (66%), and patients volunteered such information in 80 visits (67%).
      Frequency of assessment differed by clinician discipline (p<.05) and by patient
      ethnicity (p=.06). Qualitative analysis revealed characteristics of appropriate
      assessments, such as formulating the contribution of physical conditions in the
      psychiatric differential diagnosis, noting physical side effects of medications,
      adjusting treatment plans, encouraging patient contact with primary care
      providers, and promoting physical health care. CONCLUSIONS: Assessment of
      physical illness is relatively common among mental health clinicians but was
      lacking in one-third of the cases in this study, until raised by patients.
      Because frequency of assessment differed by clinician discipline and patient
      ethnicity, innovations in patient assessment and clinician education are needed
      to address disparities in management of physical illness among individuals with
      mental illness.

PMID- 20044416
TI  - Financial incentives and accountability for integrated medical care in Department
      of Veterans Affairs mental health programs.
AB  - OBJECTIVE: This study assessed the extent to which mental health leaders perceive
      their programs as being primarily accountable for monitoring general medical
      conditions among patients with serious mental illness, and it assessed
      associations with modifiable health system factors. METHODS: As part of the
      Department of Veterans Affairs (VA) 2007 national Mental Health Program Survey,
      108 mental health program directors were queried regarding program
      characteristics. Perceived accountability was defined as whether their providers,
      as opposed to external general medical providers, were primarily responsible for
      specific clinical tasks related to serious mental illness treatment or high-risk
      behaviors. Multivariable logistic regression was used to determine whether
      financial incentives or other system factors were associated with accountability.
      RESULTS: Thirty-six percent of programs reported primary accountability for
      monitoring diabetes and cardiovascular risk after prescription of second
      generation antipsychotics, 10% for hepatitis C screening, and 17% for obesity
      screening and weight management. In addition, 18% and 27% of program leaders,
      respectively, received financial bonuses for high performance for screening for
      risk of diabetes and cardiovascular disease and for alcohol misuse. Financial
      bonuses for diabetes and cardiovascular screening were associated with primary
      accountability for such screening (odds ratio=5.01, p<.05). Co-location of
      general medical providers was associated with greater accountability for high
      risk behavior screening or treatment. CONCLUSIONS: Financial incentives to
      improve quality performance may promote accountability in monitoring diabetes and
      cardiovascular risk assessment within mental health programs. Integrated care
      strategies (co-location) might be needed to promote management of high-risk
      behaviors among patients with serious mental illness.

PMID- 20044417
TI  - General medical problems of incarcerated persons with severe and persistent
      mental illness: a population-based study.
AB  - OBJECTIVE: Persons with severe mental illness have higher rates of chronic
      general medical illness compared with the general population. Similarly, compared
      with the general population, incarcerated persons have higher rates of chronic
      medical illness; however, there is little information about the synergy between
      severe mental illness and incarceration and the general medical problems of
      consumers. To address this gap in the literature this study addressed the
      following question: are consumers with a history of incarceration at greater risk
      of general medical problems compared with consumers without such a history?
      METHODS: Administrative data were used to compare the medical problems of 3,690
      persons with severe mental illness with a history of incarceration and 2,042
      persons with severe mental illness with no such history. RESULTS: Consumers with
      a history of incarceration were more likely than those with no such history to
      have infectious, blood, and skin diseases and a history of injury. Furthermore,
      when analyses controlled for gender, race, age, and substance use disorders,
      consumers with an incarceration history were 40% more likely to have any general
      medical problem and 30% more likely to have multiple medical problems.
      CONCLUSIONS: The findings presented here call for better communication among
      local public health and mental health providers and jails and better integration
      of primary care and behavioral health care among community mental health
      providers. Also, research should be accelerated on evidence-based interventions
      designed to divert persons with severe mental illness from the criminal justice
      system and facilitate community reentry for persons with severe mental illness
      who are released from jails and prisons.

PMID- 20044418
TI  - Correlates of perceived need for mental health care among active military
      personnel.
AB  - OBJECTIVE: There is increasing concern about mental health problems and need for
      mental health care among soldiers after deployment. This study examined
      correlates of self-perceived need for mental health care among active military
      personnel. METHODS: Data were from a 2002 cross-sectional population-based survey
      of 8,441 active Canadian military personnel (2,592 women) aged 16 to 54 (response
      rate 81%). A fully structured lay-administered interview for past-year DSM-IV
      mental disorders and perceived need for mental health care was conducted. Five
      domains of self-perceived need were assessed: information, medication,
      counseling, social intervention, and skills training. Several deployment factors
      were assessed (length of deployment, number of deployments, and exposure to
      deployment-related traumatic events), as were long-term restriction in activities
      because of disability and suicidal ideation. Multiple logistic regression models
      were used to determine correlates of perceived need. RESULTS: After adjustment
      for mental disorders, the strongest and most consistent correlates of perceived
      need were long-term restriction in activities, suicidal ideation, female gender,
      and regular service status (versus reserve status) (adjusted odds ratios ranging
      from 1.28 to 4.37). Deployment and exposure to combat and witnessing atrocities
      were moderately associated with an increase in self-perceived need for mental
      health care. CONCLUSIONS: The findings suggest that a range of issues beyond the
      presence of common mental disorders need to be considered in understanding the
      factors that contribute to a sense of need for mental health treatment.
      Postdeployment screening programs should consider systematically assessing self
      perceived need for mental health treatment.

PMID- 20044419
TI  - Treatment receipt by veterans after a PTSD diagnosis in PTSD, mental health, or
      general medical clinics.
AB  - OBJECTIVE: Despite the high prevalence of posttraumatic stress disorder (PTSD)
      among veterans treated at Department of Veterans Affairs (VA) facilities, rates
      of initiation of mental health treatment and persistence in treatment are
      unknown. This study examined outpatient treatment participation among veterans
      with a recent PTSD diagnosis and treatment differences according to the VA sector
      in which they received the diagnosis (PTSD specialty treatment program, general
      mental health clinic, and general medical clinic). METHODS: Administrative data
      for 20,284 veterans who had received a diagnosis of PTSD at VA facilities were
      analyzed to determine rates of treatment initiation (any psychotropic
      prescription, an antidepressant prescription, behavioral counseling, and either a
      prescription or counseling) and maintenance of pharmacotherapy (at least four 30
      day supplies), and counseling (at least eight visits) for the six months after
      diagnosis. RESULTS: Approximately two-thirds of the sample initiated treatment:
      50% received a psychotropic medication and 39% received some counseling; 64%
      received either medication or counseling. About half of those given medication
      (54%) received at least a four-month supply, and 24% of those given counseling
      had at least eight sessions. Overall, 33% received minimally adequate treatment.
      Initiation, type, and duration varied by treatment sector: receipt of a diagnosis
      in a PTSD specialty program or a mental health clinic conferred small but
      significant benefits over receipt in a general medical clinic. CONCLUSIONS:
      Greater availability of mental health specialty services, particularly PTSD
      services, may be needed to ensure that veterans receive minimally adequate
      treatment after a PTSD diagnosis.

PMID- 20044420
TI  - Subgroups of New York City children at high risk of PTSD after the September 11
      attacks: a signal detection analysis.
AB  - OBJECTIVE: Case finding is an important challenge in mental health programs
      responding to large-scale disasters. Most people who experience psychological
      symptoms after such events return to normal functioning within a few months. Yet
      a significant minority continues to experience enduring symptoms. This study
      demonstrated the use of signal detection analyses of community survey data to
      identify subgroups of children who were at highest risk of posttraumatic stress
      disorder (PTSD) after the September 11 attacks. METHODS: This study reanalyzed
      results of a needs assessment survey conducted six months after the World Trade
      Center attacks on September 11, 2001, with a representative sample of 7,832 New
      York City public school students in grades 4 to 12. Receiver operating
      characteristic (ROC) analyses conducted on half the sample resulted in a decision
      tree for classifying children into groups at varying levels of risk of PTSD.
      These decision rules were subsequently retested on the second half of the sample.
      RESULTS: We could reliably classify children into groups with varying
      probabilities of screening positive on a PTSD screen. Nearly two-thirds of
      children in grades 4 to 12 who screened positive for probable PTSD were
      concentrated among 4th graders (35%) and among children who had a friend or
      family member directly exposed to the attacks (28%). CONCLUSIONS: Signal
      detection analysis of community needs assessment surveys can identify community
      subgroups most likely to screen positive for mental health problems after a
      disaster or terrorist attack. This information can help target screening and
      outreach efforts to community segments that have the highest need for services.

PMID- 20044421
TI  - Health care infrastructure post-Katrina: disaster planning to return health care
      workers to their home communities.
AB  - One of the greatest challenges of restoring the New Orleans health care
      infrastructure since the post-Katrina disaster has been shortages of health care
      providers. Many providers had prolonged displacements or did not return to their
      practices, depleting the city of valuable resources. This Open Forum chronicles
      the displacement of Louisiana State University's Department of Psychiatry and
      discusses barriers to returning health care providers to their communities
      expeditiously. Predisaster planning and policy changes are proposed to facilitate
      a quicker return and decrease the attrition of health care providers after future
      disasters. A community's predisaster plans should include a mechanism to allow
      funds to follow patients instead of hospitals, to provide bridge funding that
      pays local health care providers to work as first responders and serve uninsured
      patients while these providers rebuild their practices, and to provide funds to
      quickly expand services and usable space in undamaged clinics and hospitals and
      to shore up reparable structures.

PMID- 20044422
TI  - Use of mental health services by nursing home residents after hurricanes.
AB  - OBJECTIVE: A growing body of research supports the value of mental health
      intervention to treat people affected by disasters. This study used a mixed
      methods approach to evaluate pre- and posthurricane mental health service use in
      Florida nursing homes. METHODS: A questionnaire was administered to 258 directors
      of nursing, administrators, and owners of nursing homes, representing two-thirds
      of Florida's counties, to identify residents' mental health needs and service
      use. In four subsequent focus group meetings with 22 nursing home administrators,
      underlying factors influencing residents' use of services were evaluated.
      RESULTS: Although most nursing homes provided some type of mental health care
      during normal operations, disaster-related mental health services were not
      routinely provided to residents. Receiving facilities were more likely than
      evacuating facilities to provide treatment to evacuated residents. CONCLUSIONS:
      Nursing home staff should be trained to deliver disaster-related mental health
      intervention and in procedures for making referrals for follow-up evaluation and
      formal intervention.

PMID- 20044423
TI  - Depression and increased short-term hospitalization risk among geriatric patients
      receiving home health care services.
AB  - OBJECTIVE: This study evaluated the association between depression and
      hospitalization among geriatric home care patients. METHODS: A sample of 477
      patients newly admitted to home care over two years was assessed for depression.
      Bivariate and logistic regression analyses examined the likelihood of
      hospitalization during a 60-day home care episode. RESULTS: The hospitalization
      rate was similar for the 77 depressed patients and 400 nondepressed patients
      (about 7%). However, mean time to hospitalization was 8.4 versus 19.5 days after
      start of care, respectively. Hospitalization risk was significantly higher for
      depressed patients during the first few weeks. A main effect for depression and a
      depression-by-time interaction was found when analyses controlled for medical
      comorbidity, cognitive status, age, gender, race, activities of daily living and
      instrumental activities of daily living, and referral to home care after
      hospitalization. CONCLUSIONS: Depression appears to increase short-term risk of
      hospitalization for geriatric home care patients immediately after starting home
      care.

PMID- 20044424
TI  - Follow-up visits by provider specialty for patients with major depressive
      disorder initiating antidepressant treatment.
AB  - OBJECTIVES: This study examined the association between provider specialty and
      guideline-concordant care after the initiation of antidepressant treatment.
      METHODS: Medical and prescription claims were analyzed from adults newly
      diagnosed as having major depressive disorder who initiated antidepressant
      treatment. Follow-up visits during the first 90 days after the index prescription
      were identified, and an indicator for receipt of guideline-concordant care (three
      or more visits) was created. Logistic regression models were used, and propensity
      score matching techniques were applied. Sensitivity analyses were conducted to
      investigate how results differed by varying the approach to identify follow-up
      visits. RESULTS: The study included 4,102 patients, and only 31% received
      guideline-concordant follow-up visits. Patients receiving their initial
      prescription from psychiatrists were nearly five times as likely as patients
      receiving their initial prescription from primary care providers to receive
      guideline-concordant follow-up care (odds ratio=4.6, 95% confidence interval=3.9
      5.4). CONCLUSIONS: Routine care for antidepressant management falls short of
      guideline recommendations, especially in primary care.

PMID- 20044425
TI  - Patterns of service use in two types of managed behavioral health care plans.
AB  - OBJECTIVE: The study examined service use patterns by level of care in two
      managed care plans offered by a national managed behavioral health care
      organization (MBHO): an employee assistance program (EAP) combined with a
      standard behavioral health plan (integrated plan) and a standard behavioral
      health plan. METHODS: The cross-sectional analysis used 2004 administrative data
      from the MBHO. Utilization of 11 specific service categories was compared. The
      weighted sample reflected exact matching on sociodemographic characteristics
      (unweighted N=710,014; weighted N=286,750). RESULTS: A larger proportion of
      enrollees in the integrated plan than in the standard plan used outpatient mental
      health and substance abuse office visits (including EAP visits) (p<.01) and
      substance abuse intensive outpatient or day treatment (p<.05), and the proportion
      using residential substance abuse rehabilitation was lower (p<.05). CONCLUSIONS:
      The integrated and standard products had distinct utilization patterns in this
      large MBHO. In particular, greater use of certain outpatient services was
      observed in the integrated plan.

PMID- 20044426
TI  - Program characteristics associated with testing for HIV and hepatitis C in
      veterans substance use disorder clinics.
AB  - OBJECTIVE: This study examined whether organizational characteristics and quality
      improvement initiatives were related to HIV and hepatitis C (HCV) testing rates
      in veterans' substance use disorders programs. METHODS: Data were collected by
      surveying 232 program directors at all U.S. Department of Veterans Affairs (VA)
      substance use disorder programs. RESULTS: Program directors (N=223) reported
      that, on average, 35% of their patients were tested for HIV (median=10%) and 57%
      were tested for HCV (median=80%). Of the quality improvement initiatives
      examined, computerized reminders to clinicians (p=.02) and a designated clinician
      for screening (p=.01) were positively associated with HCV testing, and
      computerized templates that guide clinicians through ordering of testing were
      positively associated with HIV testing (p=.06). CONCLUSIONS: Despite national
      emphasis on HIV testing, rates of testing were lower for HIV than for HCV in
      programs serving veterans with substance use disorders and at risk of both
      illnesses. System-level quality improvement initiatives may be effective at
      increasing rates of infectious disease screening.

PMID- 20044428
TI  - Where are the psychiatric physician assistants?

PMID- 20044429
TI  - The internet, health promotion, and community participation.

PMID- 20044430
TI  - Maltreatment and mental health care: focusing on child neglect.

PMID- 20044431
TI  - Closer look needed at youths in adult facilities.

PMID- 20044434
TI  - Action plans for psychiatric services.

PMID- 20044435
TI  - Functional contribution of CXCR2 to lung injury after aspiration of acid and
      gastric particulates.
AB  - The effects of individual ELR+ CXC chemokines have been documented in
      experimental models of acid aspiration. However, aspiration lung injury would be
      influenced by the combined effects of these chemokines and other factors related
      to their function. Therefore, the role of the chemokine receptor CXCR2 was
      examined in lung injury induced by aspiration of acid and acid with gastric
      particulates. Anesthetized mice were given intratracheal injections of saline,
      acid solution, or acid containing gastric particles. Within 6 h, bronchoalveolar
      lavage fluid neutrophils and albumin increased relative to the severity of the
      insult. Immunohistochemistry and RT-PCR demonstrated striking increases in
      pulmonary expression of CXCR2 after aspiration. In CXCR2-deficient mice,
      neutrophil recruitment to airways was significantly reduced after aspiration of
      either acid or acid with particles. However, lung injury scores were unaffected
      in Ccr2-/- mice in the acid + particles group. Esterase-stained lung tissue
      demonstrated that focal aggregates of inflammatory cells contained neutrophils in
      the Ccr2-/- mice. These studies suggest CXCR2 and its ligands are dominant
      mediators of neutrophil recruitment to airways after aspiration. However, CXCR2
      independent mechanisms recruit neutrophils into areas of cellular aggregation
      after aspiration of acidified gastric particulates.

PMID- 20044436
TI  - Regulation of acid signaling in rat pulmonary sensory neurons by protease
      activated receptor-2.
AB  - Airway acidification has been consistently observed in airway inflammatory
      conditions and is known to cause cardiorespiratory symptoms that are, at least in
      part, mediated through the activation of bronchopulmonary C fibers and the
      subsequent reflexes. Protease-activated receptor-2 (PAR(2)) is expressed in a
      variety of cells in the lung and airways and is believed to play a role in airway
      inflammation and hyperresponsiveness. This study was carried out to investigate
      the effect of PAR(2) activation on the acid signaling in rat bronchopulmonary C
      fiber sensory neurons. Our RT-PCR results revealed the expression of mRNAs for
      transient receptor potential vanilloid receptor 1 (TRPV1) and four functional
      acid-sensing ion channel (ASIC) subunits 1a, 1b, 2a, and 3 in these sensory
      neurons. Preincubation of SLIGRL-NH(2), a specific PAR(2)-activating peptide,
      markedly enhanced the Ca(2+) transient evoked by extracellular acidification.
      Pretreatment with PAR(2) agonists significantly potentiated both acid-evoked ASIC
      and TRPV1-like whole cell inward currents. Activation of PAR(2) also potentiated
      the excitability of these neurons to acid, but not electrical stimulation. In
      addition, the potentiation of acid-evoked responses was not prevented by
      inhibiting either PLC or PKC nor was mimicked by activation of PKC. In
      conclusion, activation of PAR(2) modulates the acid signaling in pulmonary
      sensory neurons, and the interaction may play a role in the pathogenesis of
      airway inflammatory conditions, where airway acidification and PAR(2) activation
      can occur simultaneously.

PMID- 20044437
TI  - A novel approach to analyze gene expression data demonstrates that the DeltaF508
      mutation in CFTR downregulates the antigen presentation pathway.
AB  - Gene array studies comparing cystic fibrosis (CF) and non-CF genotypes should
      reveal factors that explain variability in CF lung disease progression, yielding
      insights that lead to improved CF care. To date, studies have reached conflicting
      conclusions, perhaps due to experimental differences and divergent statistical
      approaches. This review aims: 1) to summarize the findings of four recent gene
      studies comparing CF and non-CF genotypes, and 2) to reanalyze original data
      using a recently developed statistical approach, with the aim of identifying
      genes and paths consistently regulated by the CF genotype. We identified four
      studies evaluating the effect of the DeltaF508-CFTR mutation on human airway
      epithelial cell gene expression, restricting our investigation to human airway
      epithelial cell studies whose data were accessible in NCBI's Gene Expression
      Omnibus or the European Bioinformatic Institute's ArrayExpress. Gene expression
      patterns showed consistent repression of MHC class I antigen presentation genes
      in CF human airway epithelia, suggesting a novel mechanistic explanation for poor
      clearance of viral and bacterial infections by CF patients. We also examined
      proinflammatory and NF-kappaB genes, whose induction is widely accepted as a
      hallmark of the CF genotype, but found little evidence of induction, consistent
      with a recent review (Machen TE, Am J Physiol Cell Physiol 291: C218-C230,
      2006.). In conclusion, our analysis suggests that the CF genotype may impair
      immune function in airway epithelial cells but may not increase inflammation.
      Additional studies are required to determine whether MHC class I gene repression
      in CF reduces antigen presentation at the protein level and whether repression
      impairs immune function.

PMID- 20044438
TI  - A gain-of-function mutation of Arabidopsis lipid transfer protein 5 disturbs
      pollen tube tip growth and fertilization.
AB  - During compatible pollination of the angiosperms, pollen tubes grow in the pistil
      transmitting tract (TT) and are guided to the ovule for fertilization. Lily
      (Lilium longiflorum) stigma/style Cys-rich adhesin (SCA), a plant lipid transfer
      protein (LTP), is a small, secreted peptide involved in pollen tube adhesion
      mediated guidance. Here, we used a reverse genetic approach to study biological
      roles of Arabidopsis thaliana LTP5, a SCA-like LTP. The T-DNA insertional gain-of
      function mutant plant for LTP5 (ltp5-1) exhibited ballooned pollen tubes, delayed
      pollen tube growth, and decreased numbers of fertilized eggs. Our reciprocal
      cross-pollination study revealed that ltp5-1 results in both male and female
      partial sterility. RT-PCR and beta-glucuronidase analyses showed that LTP5 is
      present in pollen and the pistil TT in low levels. Pollen-targeted overexpression
      of either ltp5-1 or wild-type LTP5 resulted in defects in polar tip growth of
      pollen tubes and thereby decreased seed set, suggesting that mutant ltp5-1 acts
      as a dominant-active form of wild-type LTP5 in pollen tube growth. The ltp5-1
      protein has additional hydrophobic C-terminal sequences, compared with LTP5. In
      our structural homology/molecular dynamics modeling, Tyr-91 in ltp5-1, replacing
      Val-91 in LTP5, was predicted to interact with Arg-45 and Tyr-81, which are known
      to interact with a lipid ligand in maize (Zea mays) LTP. Thus, Arabidopsis LTP5
      plays a significant role in reproduction.

PMID- 20044439
TI  - LPA induces IL-6 secretion from aortic smooth muscle cells via an LPA1-regulated,
      PKC-dependent, and p38alpha-mediated pathway.
AB  - Lysophosphatidic acid (LPA) is a potent bioactive lysophospholipid. Accumulated
      evidence supports a role for LPA in inflammation. To profile LPA-induced cytokine
      production in vascular smooth muscle cells (SMCs), we used a cytokine antibody
      array system and found that LPA prominently induces the secretion of IL-6 and
      monocyte chemoattractant protein (MCP)-1 from human aortic SMCs (HASMCs). The
      mechanism by which LPA induces MCP-1 expression in SMCs has been previously
      reported. However, LPA induction of IL-6 secretion from vascular SMCs and its
      regulatory mechanism are unknown. The present study reveals that LPA induces the
      expression of IL-6 mRNA and protein in HASMCs as well as the secretion of IL-6
      protein in a time-dependent manner. Our results demonstrate that LPA-specific
      receptor 1 (LPA(1)) mediates LPA-induced IL-6 secretion and that LPA induction of
      IL-6 is independent of the EGF receptor pathway. Our data further show that PKC
      mediated p38 MAPK is responsible for the IL-6 secretion. Finally, small
      interfering RNA depletion experiments revealed that p38alpha is specifically
      responsible for the LPA-induced IL-6 secretion. The present study profiles the
      regulatory relationship between LPA and multiple cytokines in vascular SMCs for
      the first time, provides the first evidence that LPA upregulates IL-6 in vascular
      SMCs, and reveals the regulatory mechanism of LPA-induced IL-6 production in
      HASMCs. In light of the emerging roles of LPA and IL-6 in vascular inflammation,
      the understanding of the regulatory mechanism may contribute to the treatment and
      prevention of cardiovascular disorders.

PMID- 20044441
TI  - Hemoglobin encapsulation in vesicles retards NO and CO binding and O2 release
      when perfused through narrow gas-permeable tubes.
AB  - Intravenous administration of cell-free Hb induces vasoconstriction and
      circulatory disorders, presumably because of the intrinsic affinities to
      endogenous nitric oxide (NO) and carbon monoxide (CO) as vasorelaxation factors
      and because of the facilitated O(2) release that might induce autoregulatory
      vasoconstriction. We examined these gas reactions when Hb-containing solutions of
      four kinds were perfused through artificial narrow tubes at a practical Hb
      concentration (10 g/dl). Purified Hb solution, polymerized bovine Hb (Poly(B)Hb),
      encapsulated Hb [Hb-vesicles (HbV), 279 nm], and red blood cells (RBCs) were
      perfused through a gas-permeable narrow tube (25 microm inner diameter) at 1 mm/s
      centerline velocity. The level of reactions was determined microscopically based
      on the visible-light absorption spectrum of Hb. When the tube was immersed in NO
      and CO atmospheres, both NO binding and CO binding of deoxygenated Hb (deoxy-Hb)
      and Poly(B)Hb in the tube was faster than those of HbV and RBCs, and HbV and RBCs
      showed almost identical binding rates. When the tube was immersed in a N(2)
      atmosphere, oxygenated Hb and Poly(B)Hb showed much faster O(2) release than did
      HbV and RBCs. Poly(B)Hb showed a faster reaction than Hb because of the lower
      O(2) affinity of Poly(B)Hb than Hb. The diffusion process of the particles was
      simulated using Navier-Stokes and Maxwell-Stefan equations. Results clarified
      that small Hb (6 nm) diffuses laterally and mixes rapidly. However, the large
      dimension HbV shows no such rapid diffusion. The purely physicochemical
      differences in diffusivity of the particles and the resulting reactivity with gas
      molecules are one factor inducing biological vasoconstriction of Hb-based oxygen
      carriers.

PMID- 20044440
TI  - Contribution of BK(Ca) channels to local metabolic coronary vasodilation: Effects
      of metabolic syndrome.
AB  - This investigation was designed to examine the hypothesis that impaired function
      of coronary microvascular large-conductance Ca(2+)-activated K(+) (BK(Ca))
      channels in metabolic syndrome (MetS) significantly attenuates the balance
      between myocardial oxygen delivery and metabolism at rest and during exercise
      induced increases in myocardial oxygen consumption (MVo(2)). Studies were
      conducted in conscious, chronically instrumented Ossabaw swine fed a normal
      maintenance diet (11% kcal from fat) or an excess calorie atherogenic diet (43%
      kcal from fat, 2% cholesterol, 20% kcal from fructose) that induces many common
      features of MetS. Data were collected under baseline/resting conditions and
      during graded treadmill exercise before and after selective blockade of BK(Ca)
      channels with penitrem A (10 microg/kg iv). We found that the exercise-induced
      increases in blood pressure were significantly elevated in MetS swine. No
      differences in baseline cardiac function or heart rate were noted. Induction of
      MetS produced a parallel downward shift in the relationship between coronary
      venous Po(2) and MVo(2) (P < 0.001) that was accompanied by a marked release of
      lactate (negative lactate uptake) as MVo(2) was increased with exercise (P <
      0.005). Inhibition of BK(Ca) channels with penitrem A did not significantly
      affect blood pressure, heart rate, or the relationship between coronary venous
      Po(2) and MVo(2) in lean or MetS swine. These data indicate that BK(Ca) channels
      are not required for local metabolic control of coronary blood flow under
      physiological (lean) or pathophysiological (MetS) conditions. Therefore,
      diminished function of BK(Ca) channels does not contribute to the impairment of
      myocardial oxygen-supply demand balance in MetS.

PMID- 20044442
TI  - Immune regulation and vascular inflammation in genetic hypertension.
AB  - Immune cells have been implicated in the pathogenesis of hypertension. We
      hypothesized that under the influence of chromosome (chr)2, T lymphocytes
      contribute to vascular inflammation in genetic salt-sensitive hypertension.
      Normotensive (Brown Norway), hypertensive (Dahl salt-sensitive), and consomic
      rats (SSBN2; in which chr2 has been transferred from Brown Norway to Dahl rats)
      were studied. Systolic blood pressure, measured by tail cuff, and aortic
      preproendothelin mRNA, measured by quantitative RT-PCR, were elevated in Dahl
      rats compared with Brown Norway rats and were reduced in SSBN2 rats compared with
      Dahl rats (P < 0.01). Compared with Brown Norway rats, Dahl rats exhibited
      increased inflammatory markers and mediators such as nuclear translocation of the
      aortic p65 subunit of NF-kappaB as well as VCAM-1, ICAM-1, chemokine (C-C motif)
      receptor 5, and CD4 mRNA, all of which were reduced in SSBN2 rats. Aortic CD8
      mRNA was equally increased in Dahl and SSBN2 rats relative to Brown Norway rats.
      CD4(+) T cell infiltration in the aorta of SSBN2 rats was reduced compared with
      Dahl rats, whereas the aortic protein expression of Foxp3b and immunosuppressors
      transforming growth factor (TGF)-beta(1) and IL-10, the three markers associated
      with the regulatory T cell lineage, were enhanced in SSBN2 rats. Activation in
      vitro of T cells demonstrated that CD4(+)CD25(+) and CD8(+)CD25(+) cells (Tregs)
      produce IL-10 in SSBN2 rats. Thus, increased vascular inflammatory responses and
      hypertension in a genetic salt-sensitive hypertensive rodent model are reduced by
      transfer of chr2 from a normotensive strain, and this is associated with enhanced
      levels of immunosuppressive mediators.

PMID- 20044443
TI  - Chronic physical activity mitigates cerebral hypoperfusion during central
      hypovolemia in elderly humans.
AB  - This study sought to test the hypothesis that orthostasis-induced cerebral
      hypoperfusion would be less severe in physically active elderly humans (ACT
      group) than in sedentary elderly humans (SED group). The peak O(2) uptake of 10
      SED (67.1 +/- 1.4 yr) and 9 ACT (68.0 +/- 1.1 yr) volunteers was determined by a
      graded cycling exercise test (22.1 +/- 1.2 vs 35.8 +/- 1.3 ml.min(-1).kg(-1), P <
      0.01). Baseline mean arterial pressure (MAP; tonometry) and middle cerebral
      arterial blood flow velocity (V(MCA); transcranial Doppler) were similar between
      the groups (SED vs. ACT group: 91 +/- 3 vs. 87 +/- 3 mmHg and 54.9 +/- 2.3 vs.
      57.8 +/- 3.2 cm/s, respectively), whereas heart rate was higher and stroke volume
      (bioimpedance) was smaller in the SED group than in the ACT group. Central
      hypovolemia during graded lower body negative pressure (LBNP) was larger (P <
      0.01) in the ACT group than in the SED group. However, the slope of V(MCA)/LBNP
      was smaller (P < 0.05) in the ACT group (0.159 +/- 0.016 cm/s/Torr) than in the
      SED group (0.211 +/- 0.008 cm/s/Torr). During LBNP, the SED group had a greater
      augmentation of cerebral vasomotor tone (P < 0.05) and hypocapnia (P < 0.001)
      compared with the ACT group. Baseline MAP variability and V(MCA) variability were
      significantly smaller in the SED group than in the ACT group, i.e., 0.49 +/- 0.07
      vs. 1.04 +/- 0.16 (mmHg)(2) and 1.06 +/- 0.19 vs. 4.24 +/- 1.59 (cm/s)(2),
      respectively. However, transfer function gain, coherence, and phase between MAP
      and V(MCA) signals (Welch spectral estimator) from 0.08-0.18 Hz were not
      different between SED (1.41 +/- 0.18 cm.s(-1).mmHg(-1), 0.63 +/- 0.06 units, and
      38.03 +/- 6.57 degrees ) and ACT (1.65 +/- 0.44 cm.s(-1).mmHg(-1), 0.56 +/- 0.05
      units, and 48.55 +/- 11.84 degrees ) groups. We conclude that a physically active
      lifestyle improves the intrinsic mechanism of cerebral autoregulation and helps
      mitigate cerebral hypoperfusion during central hypovolemia in healthy elderly
      adults.

PMID- 20044445
TI  - The title says it all.

PMID- 20044444
TI  - Downregulated Kv4.3 expression in the RVLM as a potential mechanism for
      sympathoexcitation in rats with chronic heart failure.
AB  - Elevated central angiotensin II (ANG II) plays a critical role in the
      sympathoexcitation of chronic heart failure (CHF) by stimulating upregulated ANG
      II type 1 receptors (AT(1)R) in the rostral ventrolateral medulla (RVLM).
      However, the link between enhanced ANG II signaling and alterations in the
      electrophysiological characteristics of neurons in the RVLM remains unclear. In
      the present experiments, we screened for potentially altered genes in the medulla
      of rats with CHF that are directly related to neuronal membrane conductance using
      the Rat Genome 230 2.0 Array GeneChip. We found that CHF rats exhibited a 2.1
      fold reduction in Kv4.3 gene expression, one of the main voltage-gated K(+)
      channels, in the medulla. Real-time RT-PCR and Western blot analysis confirmed
      the downregulation of Kv4.3 in the RVLM of CHF rats. In intact animals, we found
      that microinjection of the voltage-gated potassium channel blocker, 4
      aminopyridine, into the RVLM evoked a sympathoexcitation and hypertension in both
      normal and CHF rats. CHF rats exhibited smaller responses to 4-aminopyridine than
      did normal rats. Finally, we used a neuronal cell line (CATH.a neurons) to
      explore the effect of ANG II on Kv4.3 expression and function. We found that ANG
      II treatment significantly downregulated mRNA and protein expression of Kv4.3 and
      decreased the A-type K(+) current. Employing this cell line, we also found that
      the ANG II-induced inhibition of Kv4.3 mRNA expression was attenuated by the
      superoxide scavenger Tempol and the p38 MAPK inhibitor SB-203580. The effects of
      ANG II were abolished by the AT(1)R antagonist losartan. We conclude that the
      sympathoexcitation observed in the CHF state may be due, in part, to an ANG II
      induced downregulation of Kv4.3 expression and subsequent decrease in K(+)
      current, thereby increasing the excitability of neurons in the RVLM. The ANG II
      induced inhibition of Kv4.3 mRNA expression was mediated by ANG II-AT(1)R-ROS-p38
      MAPK signaling.

PMID- 20044446
TI  - Combining biochemical and ultrasonographic markers in predicting preeclampsia: a
      systematic review.
AB  - BACKGROUND: Early identification of pregnant women at risk for preeclampsia is a
      priority to implement preventive measures. Some biochemical and ultrasonographic
      parameters have shown promising predictive performance, but so far there is no
      clinically validated screening procedure. CONTENT: Using a series of keywords, we
      reviewed electronic databases (Medline, Embase, all records to May 2009)
      reporting the performance of biological and ultrasonographic markers to predict
      preeclampsia, both single markers and combinations of markers. We analyzed the
      data according to gestational age and risk levels of the studied populations. We
      evaluated the methodological quality of included publications using QUADAS
      (quality assessment of diagnostic accuracy studies). We identified 37 relevant
      studies that assessed 71 different combinations of biochemical and
      ultrasonographic markers. Most studies were performed during the second trimester
      on small-scale high-risk populations with few cases of preeclampsia. Combinations
      of markers generally led to an increase in sensitivity and/or specificity
      compared with single markers. In low-risk populations, combinations including
      placental protein 13 (PP13), pregnancy-associated plasma protein A (PAPP-A), a
      disintegrin and metalloprotease-12 (ADAM12), activin A, or inhibin A measured in
      first or early second trimester and uterine artery Doppler in second trimester
      appear promising (sensitivity 60%-80%, specificity >80%). In high-risk
      populations, the combination of PP13 and pulsatility index in first trimester
      showed 90% sensitivity and 90% specificity in a single study limited to severe
      preeclampsia. SUMMARY: Combinations of biochemical and ultrasonographic markers
      improved the performance of early prediction of preeclampsia. From a perspective
      of integrative medicine, large population-based studies evaluating algorithms
      combining multiple markers are needed, if screening approaches are to be
      eventually implemented.

PMID- 20044447
TI  - High-throughput assay to measure oxygen consumption in digitonin-permeabilized
      cells of patients with mitochondrial disorders.
AB  - BACKGROUND: Muscle biopsy analysis is regarded as the gold standard in diagnostic
      workups of patients with suspected mitochondrial disorders. Analysis of cultured
      fibroblasts can provide important additional diagnostic information. The
      measurement of individual OXPHOS complexes does not always provide sufficient
      information about the functional state of the complete mitochondrial energy
      generating system. Thus, we optimized a high-throughput fluorescence-based
      methodology for oxygen consumption analysis in patient-derived cells. METHODS: We
      analyzed mitochondrial respiration in digitonin-permeabilized cells in the
      presence of a substrate mix containing pyruvate and malate, using a
      phosphorescent probe, 96-well plates, and a fluorescence plate reader. RESULTS:
      In control fibroblasts, we observed clear stimulation by ADP of the pyruvate +
      malate-driven respiration. Known inhibitors of the OXPHOS system and the Krebs
      cycle significantly reduced respiration. In patient fibroblasts with different
      OXPHOS deficiencies, ADP-stimulated respiratory activity was decreased in
      comparison to control cells. In several patients with reduced ATP production rate
      in muscle tissue but with normal OXPHOS enzyme activities, the fibroblasts
      displayed reduced respiratory activity. Finally, we observed a clear difference
      between control and complex I-deficient transmitochondrial cybrid cells.
      CONCLUSIONS: These results confirm the validity of the assay as a high-throughput
      screening method for mitochondrial function in digitonin-permeabilized cells. The
      assay allows primary and secondary mitochondrial abnormalities in muscle to be
      differentiated, which is of great importance with respect to counseling, and also
      will facilitate the search for new genetic defects that lead to mitochondrial
      disease.

PMID- 20044448
TI  - Identification and functional characterization of monofunctional ent-copalyl
      diphosphate and ent-kaurene synthases in white spruce reveal different patterns
      for diterpene synthase evolution for primary and secondary metabolism in
      gymnosperms.
AB  - The biosynthesis of the tetracyclic diterpene ent-kaurene is a critical step in
      the general (primary) metabolism of gibberellin hormones. ent-Kaurene is formed
      by a two-step cyclization of geranylgeranyl diphosphate via the intermediate ent
      copalyl diphosphate. In a lower land plant, the moss Physcomitrella patens, a
      single bifunctional diterpene synthase (diTPS) catalyzes both steps. In contrast,
      in angiosperms, the two consecutive cyclizations are catalyzed by two distinct
      monofunctional enzymes, ent-copalyl diphosphate synthase (CPS) and ent-kaurene
      synthase (KS). The enzyme, or enzymes, responsible for ent-kaurene biosynthesis
      in gymnosperms has been elusive. However, several bifunctional diTPS of
      specialized (secondary) metabolism have previously been characterized in
      gymnosperms, and all known diTPSs for resin acid biosynthesis in conifers are
      bifunctional. To further understand the evolution of ent-kaurene biosynthesis as
      well as the evolution of general and specialized diterpenoid metabolisms in
      gymnosperms, we set out to determine whether conifers use a single bifunctional
      diTPS or two monofunctional diTPSs in the ent-kaurene pathway. Using a
      combination of expressed sequence tag, full-length cDNA, genomic DNA, and
      targeted bacterial artificial chromosome sequencing, we identified two candidate
      CPS and KS genes from white spruce (Picea glauca) and their orthologs in Sitka
      spruce (Picea sitchensis). Functional characterization of the recombinant enzymes
      established that ent-kaurene biosynthesis in white spruce is catalyzed by two
      monofunctional diTPSs, PgCPS and PgKS. Comparative analysis of gene structures
      and enzyme functions highlights the molecular evolution of these diTPSs as
      conserved between gymnosperms and angiosperms. In contrast, diTPSs for
      specialized metabolism have evolved differently in angiosperms and gymnosperms.

PMID- 20044449
TI  - ZmPIN1-mediated auxin transport is related to cellular differentiation during
      maize embryogenesis and endosperm development.
AB  - To study the influence of PINFORMED1 (PIN1)-mediated auxin transport during
      embryogenesis and endosperm development in monocots, the expression pattern of
      the three identified ZmPIN1 genes was determined at the transcript level.
      Localization of the corresponding proteins was also analyzed during maize (Zea
      mays) kernel development. An anti-indole-3-acetic acid (IAA) monoclonal antibody
      was used to visualize IAA distribution and correlate the direction of auxin
      active transport, mediated by ZmPIN1 proteins, with the actual amount of auxin
      present in maize kernels at different developmental stages. ZmPIN1 genes are
      expressed in the endosperm soon after double fertilization occurs; however,
      unlike other tissues, the ZmPIN1 proteins were never polarly localized in the
      plasma membrane of endosperm cells. ZmPIN1 transcripts and proteins also
      colocalize in developing embryos, and the ZmPIN1 proteins are polarly localized
      in the embryo cell plasma membrane from the first developmental stages,
      indicating the existence of ZmPIN1-mediated auxin fluxes. Auxin distribution
      visualization indicates that the aleurone, the basal endosperm transfer layer,
      and the embryo-surrounding region accumulate free auxin, which also has a maximum
      in the kernel maternal chalaza. During embryogenesis, polar auxin transport
      always correlates with the differentiation of embryo tissues and the definition
      of the embryo organs. On the basis of these reports and of the observations on
      tissue differentiation and IAA distribution in defective endosperm-B18 mutant and
      in N-1-naphthylphthalamic acid-treated kernels, a model for ZmPIN1-mediated
      transport of auxin and the related auxin fluxes during maize kernel development
      is proposed. Common features between this model and the model previously proposed
      for Arabidopsis (Arabidopsis thaliana) are discussed.

PMID- 20044450
TI  - WOX4 promotes procambial development.
AB  - Plant shoot organs arise from initial cells that are recruited from meristematic
      tissues. Previous studies have shown that members of the WUSCHEL-related HOMEOBOX
      (WOX) gene family function to organize various initial cell populations during
      plant development. The function of the WOX4 gene is previously undescribed in any
      plant species. Comparative analyses of WOX4 transcription and function are
      presented in Arabidopsis (Arabidopsis thaliana), a simple-leafed plant with
      collateral vasculature, and in tomato (Solanum lycopersicum), a dissected-leafed
      species with bicollateral venation. WOX4 is transcribed in the developing
      vascular bundles of root and shoot lateral organs in both Arabidopsis and tomato.
      RNA interference-induced down-regulation of WOX4 in Arabidopsis generated small
      plants whose vascular bundles accumulated undifferentiated ground tissue and
      exhibited severe reductions in differentiated xylem and phloem. In situ
      hybridization analyses of Atwox4-RNA interference plants revealed delayed and
      reduced expression of both the phloem developmental marker ALTERED PHLOEM1 and
      HOMEOBOX GENE8, a marker of the vascular procambium. Overexpression of SlWOX4
      correlated with overproliferation of xylem and phloem in transgenic tomato
      seedlings. The cumulative data suggest that the conserved WOX4 function is to
      promote differentiation and/or maintenance of the vascular procambium, the
      initial cells of the developing vasculature.

PMID- 20044453
TI  - The European Respiratory Society, 1990-2010: a 20-year anniversary story of
      success.

PMID- 20044451
TI  - The RON1/FRY1/SAL1 gene is required for leaf morphogenesis and venation
      patterning in Arabidopsis.
AB  - To identify genes involved in vascular patterning in Arabidopsis (Arabidopsis
      thaliana), we screened for abnormal venation patterns in a large collection of
      leaf shape mutants isolated in our laboratory. The rotunda1-1 (ron1-1) mutant,
      initially isolated because of its rounded leaves, exhibited an open venation
      pattern, which resulted from an increased number of free-ending veins. We
      positionally cloned the RON1 gene and found it to be identical to FRY1/SAL1,
      which encodes an enzyme with inositol polyphosphate 1-phosphatase and 3' (2'),5'
      bisphosphate nucleotidase activities and has not, to our knowledge, previously
      been related to venation patterning. The ron1-1 mutant and mutants affected in
      auxin homeostasis share perturbations in venation patterning, lateral root
      formation, root hair length, shoot branching, and apical dominance. These
      similarities prompted us to monitor the auxin response using a DR5-GUS auxin
      responsive reporter transgene, the expression levels of which were increased in
      roots and reduced in leaves in the ron1-1 background. To gain insight into the
      function of RON1/FRY1/SAL1 during vascular development, we generated double
      mutants for genes involved in vein patterning and found that ron1 synergistically
      interacts with auxin resistant1 and hemivenata-1 but not with cotyledon vascular
      pattern1 (cvp1) and cvp2. These results suggest a role for inositol metabolism in
      the regulation of auxin responses. Microarray analysis of gene expression
      revealed that several hundred genes are misexpressed in ron1-1, which may explain
      the pleiotropic phenotype of this mutant. Metabolomic profiling of the ron1-1
      mutant revealed changes in the levels of 38 metabolites, including myoinositol
      and indole-3-acetonitrile, a precursor of auxin.

PMID- 20044452
TI  - AraGEM, a genome-scale reconstruction of the primary metabolic network in
      Arabidopsis.
AB  - Genome-scale metabolic network models have been successfully used to describe
      metabolism in a variety of microbial organisms as well as specific mammalian cell
      types and organelles. This systems-based framework enables the exploration of
      global phenotypic effects of gene knockouts, gene insertion, and up-regulation of
      gene expression. We have developed a genome-scale metabolic network model
      (AraGEM) covering primary metabolism for a compartmentalized plant cell based on
      the Arabidopsis (Arabidopsis thaliana) genome. AraGEM is a comprehensive
      literature-based, genome-scale metabolic reconstruction that accounts for the
      functions of 1,419 unique open reading frames, 1,748 metabolites, 5,253 gene
      enzyme reaction-association entries, and 1,567 unique reactions compartmentalized
      into the cytoplasm, mitochondrion, plastid, peroxisome, and vacuole. The curation
      process identified 75 essential reactions with respective enzyme associations not
      assigned to any particular gene in the Kyoto Encyclopedia of Genes and Genomes or
      AraCyc. With the addition of these reactions, AraGEM describes a functional
      primary metabolism of Arabidopsis. The reconstructed network was transformed into
      an in silico metabolic flux model of plant metabolism and validated through the
      simulation of plant metabolic functions inferred from the literature. Using
      efficient resource utilization as the optimality criterion, AraGEM predicted the
      classical photorespiratory cycle as well as known key differences between redox
      metabolism in photosynthetic and nonphotosynthetic plant cells. AraGEM is a
      viable framework for in silico functional analysis and can be used to derive new,
      nontrivial hypotheses for exploring plant metabolism.

PMID- 20044454
TI  - Does cannabis use predispose to chronic airflow obstruction?

PMID- 20044455
TI  - Beyond arterial remodelling: pulmonary venous and cardiac involvement in patients
      with systemic sclerosis-associated pulmonary arterial hypertension.

PMID- 20044456
TI  - Combined pulmonary fibrosis and emphysema: a high-pressure situation.

PMID- 20044457
TI  - Is COPD in adulthood really so far removed from early development?

PMID- 20044458
TI  - European Respiratory Society guidelines for the diagnosis and management of
      lymphangioleiomyomatosis.

PMID- 20044460
TI  - What lessons have been learnt from animal models of MRSA in the lung?
AB  - Staphylococcus aureus is one of the most common causes of nosocomial pneumonia
      contributing to significant morbidity and mortality. Therapeutic options for
      patients with methicillin-resistant S. aureus (MRSA) infection are limited. In
      addition, little is known about the S. aureus virulence factors that may
      influence the presentation and prognosis of severe lower respiratory tract
      infections. Animal models of severe pneumonia allow investigators to control and
      exclude potential confounders and to examine the influence of comorbid
      conditions. Therefore, these models may improve our knowledge of the intimate
      pathophysiological mechanisms affecting pharmacodynamics, pharmacokinetics and
      efficacy of therapy. So far, animal research studies on MRSA and vancomycin
      resistant S. aureus, performed both in small and large animal models, have
      improved knowledge of the mechanisms of disease, which may lead to a better
      treatment for this severe and complex infection in humans.

PMID- 20044459
TI  - Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV
      and COPD.
AB  - Tuberculosis (TB), smoking, HIV and chronic obstructive pulmonary disease (COPD)
      are burgeoning epidemics in developing countries. The link between TB and HIV is
      well established. Less well recognised is the strong relationship between tobacco
      smoking and the development and natural history of TB. These associations are of
      considerable relevance to public health and disease outcomes in individuals with
      TB. Moreover, tobacco smoking, a modifiable risk factor, is associated with
      poorer outcomes in HIV-associated opportunistic infections, of which TB is the
      commonest in developing countries. It is now also becoming clear that TB, like
      tobacco smoke, besides its known consequences of bronchiectasis and other
      pulmonary morbidity, is also a significant risk factor for the development of
      COPD. Thus, there is a deleterious and synergistic interaction between TB, HIV,
      tobacco smoking and COPD in a large proportion of the world's population. Further
      work, specifically mechanistic and epidemiological studies, is required to
      clarify the role of tobacco smoke on the progression of TB and HIV infection, and
      to assess the impact of smoking cessation interventions. These interactions
      deserve urgent attention and have major implications for coordinated public
      health planning and policy recommendations in the developing world.

PMID- 20044461
TI  - Treatment of extensive-stage small cell lung carcinoma: current status and future
      prospects.
AB  - Small cell lung cancer (SCLC) is an aggressive lung tumour strongly associated
      with cigarette smoking, with patients often presenting with metastatic disease at
      the time of diagnosis. Although SCLC is very chemoradiosensitive and high
      response rates are obtained with treatment, relapse rates are high and the
      prognosis remains very poor. In limited-stage SCLC, the overall survival rate has
      been significantly improved by adding dose-hyperfractionated thoracic
      radiotherapy and prophylactic cranial irradiation to systemic chemotherapy. In
      contrast, little progress has been made in the treatment of extensive-stage SCLC
      (ES-SCLC), apart from the recently documented survival gain by the addition of
      prophylactic cranial irradiation. First-line therapy in ES-SCLC currently
      consists of chemotherapy, combining a platinum drug with either etoposide or
      irinotecan as a possible alternative. New treatments are needed in order to
      improve the prognosis of ES-SCLC, as median survival with current standard
      treatment is still only 9-10 months from diagnosis. The present review focuses on
      the management of ES-SCLC, with special attention to the development of new
      treatment options.

PMID- 20044462
TI  - An unusual cause of blindness.

PMID- 20044463
TI  - Culture result of smear-positive sputum samples after 2 months of antituberculous
      treatment.

PMID- 20044464
TI  - A complication of peroral bronchoscopy.

PMID- 20044465
TI  - Pulmonary arterial hypertension in systemic sclerosis: a distinctive
      endotheliopathy?

PMID- 20044466
TI  - Effects of nanoparticles on lung damage in humans.

PMID- 20044467
TI  - Nonthrombotic pulmonary embolism.

PMID- 20044468
TI  - To the editors: express concern about the recent paper by Song et al.

PMID- 20044469
TI  - From the editors: second revision of the study by Song et al.

PMID- 20044470
TI  - Medicines for children in Europe: from proposals to practicalities.

PMID- 20044471
TI  - Can we identify a power-oriented polygenic profile?
AB  - Using the model originally developed by Williams and Folland (J Physiol 586: 113
      121, 2008), we determined 1) a "total genotype score" (TGS, from the accumulated
      combination of the 6 polymorphisms, with a maximum value of "100" for the
      theoretically optimal polygenic score) in a group of elite power athletes,
      endurance athletes, and nonathletic controls, and 2) the probability for the
      occurrence of Spanish individuals with the "perfect" power-oriented profile
      (i.e., TGS = 100). We analyzed six polymorphism that are candidates to explain
      individual variations in elite power athletic status or power phenotypes (ACE
      I/D, ACTN3 R577X, AGT Met235Thr, GDF-8 K153R, IL6 -174 G/C, and NOS3 -786T>C) in
      53 elite track and field power athletes (jumpers, sprinters), 100 nonathletic
      controls, and 100 elite endurance athletes (distance runners and road cyclists)
      (all Spanish Caucasian males). The mean TGS was significantly higher in power
      athletes (70.8 +/- 17.3) compared with endurance athletes (60.4 +/- 15.9; P <
      0.001) and controls (63.3 +/- 13.2; P = 0.012), whereas it did not differ between
      the latter two groups (P = 0.366). A total of five power athletes (9.4%, all
      sprinters) had a theoretically "optimal" TGS of 100 vs. 0 subjects in the other
      two groups. The probability of a Spanish individual possessing a theoretically
      optimal polygenic profile for up to the six candidate polymorphisms we studied
      was very small, i.e., approximately 0.2% (or 1 in 500 Spanish individuals). We
      have identified a polygenic profile that allows us, at least partly, to
      distinguish elite power athletes from both endurance athletes and nonathletic
      population.

PMID- 20044472
TI  - Energy deficit after exercise augments lipid mobilization but does not contribute
      to the exercise-induced increase in insulin sensitivity.
AB  - The content of meals consumed after exercise can impact metabolic responses for
      hours and even days after the exercise session. The purpose of this study was to
      compare the effect of low dietary carbohydrate (CHO) vs. low energy intake in
      meals after exercise on insulin sensitivity and lipid metabolism the next day.
      Nine healthy men participated in four randomized trials. During the control trial
      (CON) subjects remained sedentary. During the other three trials, subjects
      exercised [65% peak oxygen consumption (Vo(2 peak)); cycle ergometer and
      treadmill exercise] until they expended approximately 800 kcal. Dietary intake
      during CON and one exercise trial (BAL) was designed to provide sufficient energy
      and carbohydrate to maintain nutrient balance. In contrast, the diets after the
      other two exercise trials were low in either CHO (LOW-CHO) or energy (LOW-EN).
      The morning after exercise we obtained a muscle biopsy, assessed insulin
      sensitivity (S(i); intravenous glucose tolerance test) and measured lipid
      kinetics (isotope tracers). Although subjects were in energy balance during both
      LOW-CHO and CON, the lower muscle glycogen concentration during LOW-CHO vs. CON
      (402 +/- 29 vs. 540 +/- 33 mmol/kg dry wt, P < 0.01) coincided with a significant
      increase in S(i) [5.2 +/- 0.7 vs. 3.8 +/- 0.7 (mU/l)(-1) x min(-1); P < 0.05].
      Conversely, despite ingesting several hundred fewer kilocalories after exercise
      during LOW-EN compared with BAL, this energy deficit did not affect S(i) the next
      day [4.9 +/- 0.9, and 5.0 +/- 0.8 (mU/l)(-1) x min(-1)]. Maintaining an energy
      deficit after exercise had the most potent effect on lipid metabolism, as
      measured by a higher plasma triacylglycerol concentration, and increased plasma
      fatty acid mobilization and oxidation compared with when in nutrient balance.
      Carbohydrate deficit after exercise, but not energy deficit, contributed to the
      insulin-sensitizing effects of acute aerobic exercise, whereas maintaining an
      energy deficit after exercise augmented lipid mobilization.

PMID- 20044473
TI  - Signaling responses after exposure to 5 alpha-dihydrotestosterone or 17 beta
      estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular
      myocytes.
AB  - Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy.
      However, signaling pathways in cells for short (3 min) and longer term (48 h)
      treatment with 17beta-estradiol (E2) or 5 alpha-dihydrotestosterone (DHT) are
      understudied. We compared the effect of adrenergic stimulation by norepinephrine
      (NE; 1 microM) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment
      in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis,
      sarcomeric structure, gene expression, phosphorylation of extracellular signal
      regulated (ERK), and focal adhesion kinases (FAK), and phospho-FAK nuclear
      localization. NE alone elicited the expected hypertrophy and strong sarcomeric
      organization, and DHT alone gave a similar but more modest response, whereas E2
      did not alter cell size. Effects of NE dominated when used with either E2 or DHT
      with all combinations. Both sex hormones alone rapidly activated FAK but not ERK.
      Long-term or brief exposure to E2 attenuated NE-induced FAK phosphorylation,
      whereas DHT had no effect. Neither hormone altered NE-elicited ERK activation.
      Longer term exposure to E2 alone reduced FAK phosphorylation and reduced nuclear
      phospho-FAK, whereas its elevation was seen in the presence of NE with both sex
      hormones. The mitigating effects of E2 on the NE-elicited increase in cell size
      and the hypertrophic effect of DHT in NRVMs are in accordance with results
      observed in whole animal models. This is the first report of rapid, nongenomic
      sex hormone signaling via FAK activation and altered FAK trafficking to the
      nucleus in heart cells.

PMID- 20044474
TI  - A 2-wk reduction of ambulatory activity attenuates peripheral insulin
      sensitivity.
AB  - US adults take between approximately 2,000 and approximately 12,000 steps per
      day, a wide range of ambulatory activity that at the low range could increase
      risk for developing chronic metabolic diseases. Dramatic reductions in physical
      activity induce insulin resistance; however, it is uncertain if and how low
      ambulatory activity would influence peripheral insulin sensitivity. We aimed to
      explore if healthy, nonexercising subjects who went from a normal to a low level
      of ambulatory activity for 2 wk would display metabolic alterations including
      reduced peripheral insulin sensitivity. To do this, ten healthy young men
      decreased their daily activity level from a mean of 10,501+/-808 to 1,344+/-33
      steps/day for 2 wk. Hyperinsulinemic-euglycemic clamps with stable isotopes and
      muscle biopsies, maximal oxygen consumption (VO2 max) tests, and blood samples
      were performed pre- and postintervention. A reduced number of daily steps induced
      a significant reduction of 17% in the glucose infusion rate (GIR) during the
      clamp. This reduction was due to a decline in peripheral insulin sensitivity with
      no effect on hepatic endogenous glucose production. The insulin-stimulated ratio
      of pAktthr308/total Akt decreased after step reduction, with a post hoc analysis
      revealing the most pronounced effect after 4 h of insulin infusion. In addition,
      the 2-wk period induced a 7% decline in VO2 max (ml/min; cardiovascular fitness).
      Lean mass of legs, but not arms and trunk, decreased concurrently. Taken
      together, one possible biological cause for the public health problem of Type 2
      diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy,
      nonexercising young men significantly reduced peripheral insulin sensitivity,
      cardiovascular fitness, and lean leg mass.

PMID- 20044475
TI  - Eccentric exercise induces nitric oxide synthase expression through nuclear
      factor-kappaB modulation in rat skeletal muscle.
AB  - This study aimed to investigate the effect of eccentric exercise on the
      expression of the different nitric oxide synthase (NOS) isoforms in rat deep
      vastus lateralis muscle. Twenty-four rats were allocated to four experimental
      groups: rested control group, acutely exercised group after an intermittent
      downhill protocol for 90 min, acutely exercised group treated with pyrrolidine
      dithiocarbamate (100 mg/kg ip) for 24 and 1 h before the acute exercise bout, and
      acutely exercised group with a previous submaximal eccentric training of 8 wk.
      Acutely exercised rats showed increased levels of protein tyrosine nitration, NF
      kappaB binding, and phospho-I kappaB alpha content. A significant increase was
      observed in mRNA level and protein content of neuronal NOS, inducible NOS, and
      endothelial NOS. The binding of NF-kappaB to the NOS isoform promoters, measured
      by a chromatin immunoprecipitation assay, was undetectable in rested rats,
      whereas it was evident in acutely exercised animals. All of these effects were
      partially abolished by pyrrolidine dithiocarbamate treatment and by training. In
      summary, our findings provide a direct link between the NF-kappaB signaling
      cascade and NOS expression in skeletal muscle following eccentric exercise and
      suggest a modulation of the expression of the three NOS isoforms by this
      transcription factor.

PMID- 20044476
TI  - Associations of polymorphisms of eight muscle- or metabolism-related genes with
      performance in Mount Olympus marathon runners.
AB  - Athletic endurance performance is probably partly under genetic control, but
      genetic association studies have yielded inconclusive results. The objective of
      the present study was to evaluate the association of polymorphisms in eight
      muscle- or metabolism-related genes with endurance performance in participants of
      the Olympus Marathon running race. We recruited 438 athletes who participated in
      the 2007 and 2008 annual running events of the Olympus Marathon: a 43.8-km race
      with an ascent from sea level to 2,690-m altitude and then a descent to 300 m.
      Phenotypes of interest were the competitive event time at the specific Olympus
      Marathon where the athlete was enrolled, the fastest reported timing ever
      achieved in an Olympus Marathon, and how many kilometers per week the athlete ran
      during the previous year. Eleven polymorphisms in alpha(3)-actinin (ACTN3), AMP
      deaminase-1 (AMPD1), bradykinin B(2) receptor (BDKRB2), beta(2)-adrenergic
      receptor (ADRB2), peroxisome proliferator-activated receptor (PPAR)-gamma
      coactivator-1 alpha (PPARGC1A), PPAR-alpha (PPARA), PPAR-delta (PPARD), and
      apoliprotein E (APOE) were evaluated. Hardy-Weinberg equilibrium testing on the
      overall cohort of male athletes showed a significant deviation for BDKRB2
      rs1799722 (P = 0.018; P = 0.006 when limited to 316 habitual male runners) with
      an excess of the TT genotype. Across all athletes, no associations showed nominal
      statistical significance for any of the three phenotypes, and the same was true
      when analyses were limited to men (n = 417). When limited to 316 male athletes
      who identified running as their preferred sport, ADRB2 rs1042713 had nominally
      significant associations with faster times for the minor (A) allele for the
      fastest time ever (P = 0.01). The direction of effect was identical as previously
      postulated only for BDKRB2 rs1799722 and ADRB2 rs1042713, indicating consistency.
      BDKRB2 rs1799722 and ADRB2 rs1042713 have some support for being implicated in
      endurance performance among habitual runners and require further investigation.

PMID- 20044477
TI  - Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial
      biogenesis in L6 myocytes.
AB  - 5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) and caffeine, which
      activate AMP-activated protein kinase (AMPK) and cause sarcoplasmic reticulum
      calcium release, respectively, have been shown to increase mitochondrial
      biogenesis in L6 myotubes. Nitric oxide (NO) donors also increase mitochondrial
      biogenesis. Since neuronal and endothelial NO synthase (NOS) are calcium
      dependent and are also phosphorylated by AMPK, we hypothesized that NOS
      inhibition would attenuate the activation of mitochondrial biogenesis in response
      to AICAR and caffeine. L6 myotubes either were not treated (control) or were
      exposed acutely or for 5 h/day over 5 days to 100 microM of N(G)-nitro-L-arginine
      methyl ester (L-NAME, NOS inhibitor), 100 microM S-nitroso-N-acetyl-penicillamine
      (SNAP) (NO donor) +/- 100 microM L-NAME, 2 mM AICAR +/- 100 microM L-NAME, or 5
      mM caffeine +/- 100 microM L-NAME (n = 12/treatment). Acute AICAR administration
      increased (P < 0.05) phospho- (P-)AMPK, but also increased P-CaMK, with resultant
      chronic increases in peroxisome proliferator-activated receptor-gamma coactivator
      1 alpha (PGC-1 alpha), cytochrome-c oxidase (COX)-1, and COX-4 protein expression
      compared with control cells. NOS inhibition, which had no effect on AICAR
      stimulated P-AMPK, surprisingly increased P-CaMK and attenuated the AICAR-induced
      increases in COX-1 and COX-4 protein. Caffeine administration, which increased P
      CaMK without affecting P-AMPK, increased COX-1, COX-4, PGC-1 alpha, and citrate
      synthase activity. NOS inhibition, surprisingly, greatly attenuated the effect of
      caffeine on P-CaMK and attenuated the increases in COX-1 and COX-4 protein. SNAP
      increased all markers of mitochondrial biogenesis, and it also increased P-AMPK
      and P-CaMK. In conclusion, AICAR and caffeine increase mitochondrial biogenesis
      in L6 myotubes, at least in part, via interactions with NOS.

PMID- 20044478
TI  - Analysis of binding sites on complement factor I that are required for its
      activity.
AB  - The central complement inhibitor factor I (FI) degrades activated complement
      factors C4b and C3b in the presence of cofactors such as C4b-binding protein,
      factor H, complement receptor 1, and membrane cofactor protein. FI is a serine
      protease composed of two chains. The light chain comprises the serine protease
      domain, whereas the heavy chain contains several domains; that is, the FI and
      membrane attack complex domain (FIMAC), CD5, low density lipoprotein receptor 1
      (LDLr1) and LDLr2 domains. To understand better how FI acts as a complement
      inhibitor, we used homology-based models of FI domains to predict potential
      binding sites. Specific amino acids were then mutated to yield 16 well expressed
      mutants, which were then purified from media of eukaryotic cells for functional
      analyses. The Michaelis constant (K(m)) of all FI mutants toward a small
      substrate was not altered, whereas some mutants showed increased maximum initial
      velocity (V(max)). All the mutations in the FIMAC domain affected the ability of
      FI to degrade C4b and C3b irrespective of the cofactor used, whereas only some
      mutations in the CD5 and LDLr1/2 domains had a similar effect. These same mutants
      also showed impaired binding to C3met. In conclusion, the FIMAC domain appears to
      harbor the main binding sites important for the ability of FI to degrade C4b and
      C3b.

PMID- 20044479
TI  - Selective disruption of insulin-like growth factor-1 (IGF-1) signaling via
      phosphoinositide-dependent kinase-1 prevents the protective effect of IGF-1 on
      human cancer cell death.
AB  - Insulin-like growth factor-1 (IGF-1) signaling system exerts a broad
      antiapoptotic function and plays a crucial role in resistance to anticancer
      therapies. Exposure of MCF-7 breast cancer cells to IGF-1 rapidly and transiently
      induced tyrosine phosphorylation and activation of phosphoinositide-dependent
      kinase-1 (PDK1). This was paralleled by Akt/protein kinase B and protein kinase C
      zeta phosphorylation, at Thr(308) and Thr(410), respectively. IGF-1 treatment
      also enhanced PDK1 interaction with IGF-1 receptor (IGF-1R) in intact MCF-7
      cells. Pulldown assays revealed that PDK1 bound IGF-1R in vitro and that the
      region encompassing amino acids 51-359 of PDK1 was necessary for the interaction.
      Synthetic peptides corresponding to IGF-1R C terminus amino acids 1295-1337 (C43)
      and to PDK1 amino acids 114-141 reduced in vitro IGF-1R/PDK1 interaction in a
      concentration-dependent manner. Loading of fluoresceinated-C43 (fluorescein
      isothiocyanate (FITC)-C43) into MCF-7 cells significantly reduced IGF-1R/PDK1
      interaction and phosphorylation of PDK1 substrates. Moreover, FITC-C43
      intracellular loading reverted the protective effect of IGF-1 on growth factor
      deprivation-induced cell death. Finally, the inhibition of IGF-1R/PDK1
      interaction and signaling by FITC-C43 was accompanied by 2-fold enhanced killing
      capacity of cetuximab in human GEO colon adenocarcinoma cells and was sufficient
      to restore cell death in cetuximab-resistant cell clones. Thus, disruption of
      PDK1 interaction with IGF-1R reduces IGF-1 survival effects in cancer cells and
      may enhance cell death by anticancer agents.

PMID- 20044480
TI  - The cytomegalovirus UL146 gene product vCXCL1 targets both CXCR1 and CXCR2 as an
      agonist.
AB  - Large DNA viruses, such as herpesvirus and poxvirus, encode proteins that target
      and exploit the chemokine system of their host. UL146 and UL147 in the
      cytomegalovirus (CMV) genome encode the two CXC chemokines vCXCL1 and vCXCL2. In
      this study, vCXCL1 was probed against a panel of the 18 classified human
      chemokine receptors. In calcium mobilization assays vCXCL1 acted as an agonist on
      both CXCR1 and CXCR2 but did not activate or block any of the other 16 chemokine
      receptors. vCXCL1 was characterized and compared with CXCL1/GROalpha,
      CXCL2/GRObeta, CXCL3/GROgamma, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2 and
      CXCL8/IL-8 in competition binding, calcium mobilization, inositol triphosphate
      turnover, and chemotaxis assays using CXCR1- and CXCR2-expressing Chinese hamster
      ovary, 300.19, COS7, and L1.2 cells. The affinities of vCXCL1 for the CXCR1 and
      CXCR2 receptors were 44 and 5.6 nm, respectively, as determined in competition
      binding against radioactively labeled CXCL8. In calcium mobilization,
      phosphatidylinositol turnover, and chemotaxis assays, vCXCL1 acted as a highly
      efficacious activator of both receptors, with a rather low potency for the CXCR1
      receptor but comparable with CXCL5 and CXCL7. It is suggested that CMV uses the
      UL146 gene product expressed in infected endothelial cells to attract neutrophils
      by activating their CXCR1 and CXCR2 receptors, whereby neutrophils can act as
      carriers of the virus to uninfected endothelial cells. In that way a lasting pool
      of CMV-infected endothelial cells could be maintained.

PMID- 20044481
TI  - Intracellular calreticulin regulates multiple steps in fibrillar collagen
      expression, trafficking, and processing into the extracellular matrix.
AB  - Calreticulin (CRT), a chaperone and Ca(2+) regulator, enhances wound healing, and
      its expression correlates with fibrosis in animal models, suggesting that CRT
      regulates production of the extracellular matrix. However, direct regulation of
      collagen matrix by CRT has not been previously demonstrated. We investigated the
      role of CRT in the regulation of fibrillar collagen expression, secretion,
      processing, and deposition in the extracellular matrix by fibroblasts. Mouse
      embryonic fibroblasts deficient in CRT (CRT(-/-) MEFs) have reduced transcript
      levels of fibrillar collagen I and III and less soluble collagen as compared with
      wild type MEFs. Correspondingly, fibroblasts engineered to overexpress CRT have
      increased collagen type I transcript and protein. Collagen expression appears to
      be regulated by endoplasmic reticulum (ER) calcium levels and intracellular CRT,
      because thapsigargin treatment reduced collagen expression, whereas addition of
      exogenous recombinant CRT had no effect. CRT(-/-) MEFs exhibited increased ER
      retention of collagen, and collagen and CRT were co-immunoprecipitated from
      isolated cell lysates, suggesting that CRT is important for trafficking of
      collagen through the ER. CRT(-/-) MEFs also have reduced type I procollagen
      processing and deposition into the extracellular matrix. The reduced collagen
      matrix deposition is partly a consequence of reduced fibronectin matrix formation
      in the CRT-deficient cells. Together, these data show that CRT complexes with
      collagen in cells and that CRT plays critical roles at multiple stages of
      collagen expression and processing. These data identify CRT as an important
      regulator of collagen and suggest that intracellular CRT signaling plays an
      important role in tissue remodeling and fibrosis.

PMID- 20044482
TI  - A 3.5-nm structure of rat TRPV4 cation channel revealed by Zernike phase-contrast
      cryoelectron microscopy.
AB  - The transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation
      channel responsive to various stimuli including cell swelling, warm temperatures
      (27-35 degrees C), and chemical compounds such as phorbol ester derivatives. Here
      we report the three-dimensional structure of full-length rat TRPV4 purified from
      baculovirus-infected Sf9 cells. Hexahistidine-tagged rat TRPV4 (His-rTRPV4) was
      solubilized with detergent and purified through affinity chromatography and size
      exclusion chromatography. Chemical cross-linking analysis revealed that detergent
      solubilized His-rTRPV4 was a tetramer. The 3.5-nm structure of rat TRPV4 was
      determined by cryoelectron microscopy using single-particle reconstruction from
      Zernike phase-contrast images. The overall structure comprises two distinct
      regions; a larger dense component, likely corresponding to the cytoplasmic N- and
      C-terminal regions, and a smaller component corresponding to the transmembrane
      region.

PMID- 20044483
TI  - High affinity anti-inorganic material antibody generation by integrating graft
      and evolution technologies: potential of antibodies as biointerface molecules.
AB  - Recent advances in molecular evolution technology enabled us to identify peptides
      and antibodies with affinity for inorganic materials. In the field of
      nanotechnology, the use of the functional peptides and antibodies should aid the
      construction of interface molecules designed to spontaneously link different
      nanomaterials; however, few material-binding antibodies, which have much higher
      affinity than short peptides, have been identified. Here, we generated high
      affinity antibodies from material-binding peptides by integrating peptide
      grafting and phage-display techniques. A material-binding peptide sequence was
      first grafted into an appropriate loop of the complementarity determining region
      (CDR) of a camel-type single variable antibody fragment to create a low affinity
      material-binding antibody. Application of a combinatorial library approach to
      another CDR loop in the low affinity antibody then clearly and steadily promoted
      affinity for a specific material surface. Thermodynamic analysis demonstrated
      that the enthalpy synergistic effect from grafted and selected CDR loops
      drastically increased the affinity for material surface, indicating the potential
      of antibody scaffold for creating high affinity small interface units. We show
      the availability of the construction of antibodies by integrating graft and
      evolution technology for various inorganic materials and the potential of high
      affinity material-binding antibodies in biointerface applications.

PMID- 20044484
TI  - The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction.
AB  - The complement anaphylatoxin C5a is a proinflammatory component of host defense
      that functions through two identified receptors, C5a receptor (C5aR) and C5L2.
      C5aR is a classical G protein-coupled receptor, whereas C5L2 is structurally
      homologous but deficient in G protein coupling. In human neutrophils, we show
      C5L2 is predominantly intracellular, whereas C5aR is expressed on the plasma
      membrane. Confocal analysis shows internalized C5aR following ligand binding is
      co-localized with both C5L2 and beta-arrestin. Antibody blockade of C5L2 results
      in a dramatic increase in C5a-mediated chemotaxis and ERK1/2 phosphorylation but
      does not alter C5a-mediated calcium mobilization, supporting its role in
      modulation of the beta-arrestin pathway. Association of C5L2 with beta-arrestin
      is confirmed by cellular co-immunoprecipitation assays. C5L2 blockade also has no
      effect on ligand uptake or C5aR endocytosis in human polymorphonuclear
      leukocytes, distinguishing its role from that of a rapid recycling or scavenging
      receptor in this cell type. This is thus the first example of a naturally
      occurring seven-transmembrane segment receptor that is both obligately uncoupled
      from G proteins and a negative modulator of signal transduction through the beta
      arrestin pathway. Physiologically, these properties provide the possibility for
      additional fine-tuning of host defense.

PMID- 20044485
TI  - In memoriam: Alan M. Levine, MD.

PMID- 20044486
TI  - Extremity war injuries: collaborative efforts in research, host nation care, and
      disaster preparedness.
AB  - The fourth annual Extremity War Injuries (EWI) Symposium addressed ongoing
      challenges and opportunities in the management of combat-related musculoskeletal
      injury. The symposium, which also examined host-nation care and disaster
      preparedness and response, defined opportunities for synergy between several
      organizations with similar missions and goals. Within the Department of Defense,
      the Orthopaedic Extremity Trauma Research Program (OETRP) has funded basic
      research related to a series of protocols first identified and validated at prior
      EWI symposia. A well-funded clinical research arm of OETRP has been developed to
      help translate and validate research advances from each of the protocols. The
      Armed Forces Institute for Regenerative Medicine, a consortium of academic
      research institutions, employs a tissue-engineering approach to EWI challenges,
      particularly with regard to tissue loss. Programs within the National Institute
      of Arthritis and Musculoskeletal and Skin Diseases and throughout the National
      Institutes of Health have also expanded tissue-engineering efforts by emphasizing
      robust mechanistic basic science programs. Much of the clinical care delivered by
      US military medical personnel and nongovernmental agencies has been to host
      nation populations; coordinating delivery to maximize the number of injured who
      receive care requires understanding of the breadth and scope of resources
      available within the war zone. Similarly, providing the most comprehensive care
      to the greatest number of injured in the context of domestic mass casualty
      requires discussion and planning by all groups involved.

PMID- 20044487
TI  - Open tibial shaft fractures: I. Evaluation and initial wound management.
AB  - Open fractures of the tibial diaphysis are often associated with severe bone and
      soft-tissue injury. Contamination of the fracture site and devitalization of the
      soft-tissue envelope greatly increase the risk of infection, nonunion, and wound
      complications. Management of open tibial shaft fractures begins with a thorough
      patient evaluation, including assessment of the bone and soft tissue surrounding
      the tibial injury. Classification of these injuries according to the system of
      Gustilo and Anderson at the time of surgical debridement is useful in guiding
      treatment and predicting outcomes. Administration of antibiotic prophylaxis as
      soon as possible after injury as well as urgent and thorough debridement,
      irrigation, and bony stabilization are done to minimize the risk of infection and
      improve outcomes. The use of antibiotic bead pouches and negative-pressure wound
      therapy has proved to be efficacious for the acute, temporary management of
      severe bone and soft-tissue defects.

PMID- 20044489
TI  - Current treatment strategies for bicolumnar distal humerus fractures.
AB  - Management of distal humerus fractures continues to challenge orthopaedic
      surgeons. The unique and complex anatomy of the distal humerus, involving the
      ulnohumeral and radiocapitellar joints, makes anatomic reduction difficult and
      hardware placement challenging. However, long-term results of well-performed open
      reduction and internal fixation demonstrate satisfactory outcomes in most
      patients. Osteoporosis in the elderly population often leads to severe
      comminution, which may render open reduction and internal fixation impossible.
      Total elbow arthroplasty in the elderly has become a viable option, with
      excellent results in the properly selected patient who understands the lifetime
      limitations of this option. Distal humeral replacement is a new and potentially
      exciting option but it is currently not approved by the US Food and Drug
      Administration and has no long-term follow-up to support its use.

PMID- 20044490
TI  - Distal triceps rupture.
AB  - Distal triceps rupture is an uncommon injury. It is most often associated with
      anabolic steroid use, weight lifting, and laceration. Other local and systemic
      risk factors include local steroid injection, olecranon bursitis, and
      hyperparathyroidism. Distal triceps rupture is usually caused by a fall on an
      outstretched hand or a direct blow. Eccentric loading of a contracting triceps
      has been implicated, particularly in professional athletes. Initial diagnosis may
      be difficult because a palpable defect is not always present. Pain and swelling
      may limit the ability to evaluate strength and elbow range of motion. Although
      plain radiographs are helpful in ruling out other elbow pathology, MRI is used to
      confirm the diagnosis, classify the injury, and guide management. Incomplete
      tears with active elbow extension against resistance are managed nonsurgically.
      Surgical repair is indicated in active persons with complete tears and for
      incomplete tears with concomitant loss of strength. Good to excellent results
      have been reported with surgical repair, and very good results have been achieved
      even for chronic tears.

PMID- 20044491
TI  - Ambulatory assistive devices in orthopaedics: uses and modifications.
AB  - Ambulatory assistive devices (eg, canes, crutches, walkers) provide advantages
      such as stability, augmentation of muscle action, and reduction of weight-bearing
      load. Although they are often prescribed, a detailed understanding of these
      devices is often lacking, which can lead to detrimental consequences.
      Comprehension of normal gait cadence, as well as the gait patterns used in both
      reciprocating and swinging gait, allows the orthopaedic surgeon to understand the
      limitations of the patient with gait abnormalities. Appreciating the types of
      assistive devices, their modifications, associated gait patterns, physiologic
      demand, proper fitting, and indications for use is essential in prescribing the
      proper device.

PMID- 20044492
TI  - The advantage of throwing the first stone: how understanding the evolutionary
      demands of Homo sapiens is helping us understand carpal motion.
AB  - Unlike any other diarthrodial joint in the human body, the "wrist joint" is
      composed of numerous articulations between eight carpal bones, the distal radius,
      the distal ulna, and five metacarpal bones. The carpal bones articulate with each
      other as well as with the distal radius, distal ulna, and the metacarpal bases.
      Multiple theories explaining intercarpal motion have been proposed; however,
      controversy exists concerning the degree and direction of motion of the
      individual carpal bones within the two carpal rows during different planes of
      motion. Recent investigations have suggested that traditional explanations of
      carpal bone motion may not entirely account for carpal motion in all planes.
      Better understanding of the complexities of carpal motion through the use of
      advanced imaging techniques and simultaneous appreciation of human anatomic and
      functional evolution have led to the hypothesis that the "dart thrower's motion"
      of the wrist is uniquely human. Carpal kinematic research and current
      developments in both orthopaedic surgery and anthropology underscore the
      importance of the dart thrower's motion in human functional activities and the
      clinical implications of these concepts for orthopaedic surgery and
      rehabilitation.

PMID- 20044494
TI  - Responsiveness of the International Knee Documentation Committee Subjective Knee
      Form in comparison to the Western Ontario and McMaster Universities
      Osteoarthritis Index, modified Cincinnati Knee Rating System, and Short Form 36
      in patients with focal articular cartilage defects.
AB  - BACKGROUND: The International Knee Documentation Committee Subjective Knee Form
      (IKDC SKF) is a patient-reported knee-specific outcome measure that has been
      shown to be a reliable, valid, and responsive measure for patients with a variety
      of knee conditions. Further testing is required to compare the reliability and
      responsiveness of the IKDC SKF to other commonly used patient-reported outcome
      measures for patients with articular cartilage lesions. HYPOTHESIS: The IKDC SKF
      has equal or better levels of reliability and responsiveness than the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC), modified
      Cincinnati Knee Rating System (CKRS), and the Short Form 36 in patients with
      articular cartilage lesions. STUDY DESIGN: Cohort study (diagnosis); Level of
      evidence, 2. METHODS: Reliability was assessed by administering the 4 patient
      reported outcome measures to 17 individuals who had undergone articular cartilage
      surgery 5 years before participation in this study. Responsiveness was determined
      by administering the 4 patient-reported outcome measures to 51 individuals with
      diagnosed focal articular cartilage defects who were scheduled to undergo
      surgical treatment. In both groups, the outcome measures were administered at
      baseline and at 6 and 12 months' follow-up. Participants also provided a global
      rating of change in comparison to baseline at the 6- and 12-month follow-ups.
      RESULTS: Test-retest reliability coefficients were 0.91 and 0.93 for the IKDC SKF
      at the 6- and 12-month follow-ups, respectively. The effect sizes and
      standardized response means were large (>0.80) at 6 months after surgery for the
      WOMAC pain, physical function, and total scores and 12 months after surgery for
      the IKDC SKF; WOMAC pain, physical function, and total; and CKRS scores. Six
      months after surgery, significant differences between those who were improved
      compared with those who were unchanged or worse were found only for the IKDC SKF.
      Twelve months after surgery, significant differences between the improved and
      unchanged groups were found for all of the knee-specific patient-reported outcome
      measures. Finally, the IKDC SKF, WOMAC, and CKRS scores were able to
      differentiate between individuals who perceived themselves to be improved versus
      not improved and the minimum clinically important difference for the IKDC SKF was
      6.3 at 6 months and 16.7 at 12 months. CONCLUSION: The reliability and
      responsiveness of the IKDC SKF is comparable with other commonly used patient
      reported outcome measures for patients with articular cartilage lesions. The IKDC
      SKF is a suitable alternative to other commonly used knee-specific instruments
      for measuring symptoms, daily function, and level of symptom-free sports activity
      in patients undergoing articular cartilage surgery.

PMID- 20044495
TI  - Ulnar translocation of the wrist in a professional quarterback: a case report.

PMID- 20044496
TI  - Patellar height and posterior tibial slope after open- and closed-wedge high
      tibial osteotomy: a radiological study on 100 patients.
AB  - BACKGROUND: Valgus high tibial osteotomy (HTO) may be associated with changes in
      the patellar height and posterior tibial slope. HYPOTHESIS: Patellar height
      increases and posterior tibial slope decreases after closed-wedge HTO, whereas
      patellar height decreases and tibial slope increases after open-wedge osteotomy.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Lateral radiographs of
      100 knees were assessed for patellar height (PH) (Insall-Salvati index [ISI],
      Caton-De Champ index [CDI], and Blackburne-Peel index [BPI]) as well as posterior
      tibial slope. Measurements were done before HTO (50 closed wedge [CW], 50 open
      wedge [OW]), direct postoperatively, and before removal of the hardware. RESULTS:
      In the CW group, all 3 PH indices were increased direct postoperatively and at
      removal of the hardware, with changes in CDI and BPI being significant (P<.05).
      The effect size (ES) for the direct postoperative PH increase was medium (ES =
      0.48) according to CDI. In the OW group, all 3 indices showed a significant (P
      <.05) PH decrease direct postoperatively and at hardware removal. The ES for the
      direct postoperative PH decrease was large according to CDI (ES = 0.92) and BPI
      (ES = 0.80). There were no significant changes between the 2 follow-up
      measurements (P > .05) with a small ES each. Posterior tibial slope showed a
      significant (P <.05) decrease of 3.1 degrees +/- 3.4 degrees after CW HTO and a
      significant (P <.05) increase of 2.1 degrees +/- 3.6 degrees after OW HTO direct
      postoperatively. These changes did not change at the second follow-up. In CW HTO,
      the correlations between frontal plane correction and PH changes were moderate
      (CDI: r = .57; BPI: r = .64). In OW HTO, these correlations were weak (CDI: r =
      .44; BPI: r = .46). According to ISI, there was no correlation (CW: r = .11; OW:
      r = .16). There was no correlation between PH changes and slope changes (CDI) and
      no correlation between frontal plane HTO correction and slope changes in both CW
      and OW HTO. CONCLUSION: The results confirm our hypothesis for PH and posterior
      tibial slope changes after valgus HTO. However, there is no strong correlation
      between PH changes and the degree of frontal plane HTO correction. The incidence
      of patella infera increases after OW HTO, whereas the incidence of patella alta
      increases after CW HTO. Therefore, we recommend performing CW HTO or OW HTO with
      the tuberosity left at the proximal tibia in cases of patellofemoral complaints
      or patella infera. Neither technique leads to patellar lowering. It should be
      borne in mind that PH and posterior tibial slope may have been altered before
      planning total knee replacement after HTO.

PMID- 20044497
TI  - Biodegradable screw versus a press-fit bone plug fixation for hamstring anterior
      cruciate ligament reconstruction: a prospective randomized study.
AB  - BACKGROUND: Press-fit fixation of a tendon graft has been advocated to achieve
      tendon-to-bone healing. HYPOTHESIS: Fixation of hamstring tendon grafts with a
      porous bone scaffold limits bone tunnel enlargement compared with a biodegradable
      interference screw fixation. STUDY DESIGN: Randomized controlled trial; Level of
      evidence, 1. Methods Between 2005 and 2006, 20 patients (17 men, 3 women) with a
      primary reconstruction of the anterior cruciate ligament (ACL) were enrolled in
      this study. Patients were randomized to obtain graft fixation in the tibial
      tunnel either by means of an interference screw (I) or a press-fit fixation with
      a porous bone cylinder (P). At 3 months after surgery, a computed tomography (CT)
      scan of the knee was performed, and tunnel enlargement was analyzed in the
      coronal and sagittal planes for the proximal, middle, and distal thirds of the
      tunnel. After 6 months and 1 and 2 years, radiographs of the knee in the sagittal
      and coronal plane were analyzed for bone tunnel widening. The International Knee
      Documentation Committee (IKDC), Tegner, and Lysholm scores of both groups were
      compared after 1 and 2 years. RESULTS: The bone tunnel enlargement determined by
      CT was 106.9% + or - 10.9% for group P and 121.9% + or - 9.0% for group I (P <
      .02) in the anteroposterior (AP) plane and 102.8% + or - 15.2% versus 121.5% + or
      - 10.1% in the coronal plane (P <.01). The IKDC, Tegner, and Lysholm scores
      improved in both groups from preoperatively to postoperatively without
      significant differences between the 2 groups. There was a trend to higher knee
      stability in group P after 3 months (0.6 + or - 1.4 mm vs 1.8 + or - 1.5 mm; P =
      .08). CONCLUSION: Both interference screw and a press-fit fixation lead to a high
      number of good or very good outcomes after ACL reconstruction. Tibial press-fit
      fixation decreases the amount of proximal bone tunnel enlargement.

PMID- 20044498
TI  - Novel approach to repair of acute achilles tendon rupture: early recovery without
      postoperative fixation or orthosis.
AB  - BACKGROUND: Immobilization or orthosis is required after conventional Achilles
      tendon surgery. Hypothesis This new Achilles tendon repair approach enables early
      rehabilitation without any postoperative immobilization or orthosis. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: Twenty consecutive patients
      (14 men and 6 women; mean age, 43.4 years; range, 16-70 years) who had acute
      subcutaneous Achilles tendon rupture were treated by the new method, with an
      average follow-up of 2.9 years (range, 2-4.8 years). Among them, 15 injuries were
      sports-related and 5 were work-related. The authors applied a side-locking loop
      technique of their own design for the core suture, using braided polyblend suture
      thread, with peripheral cross-stitches added. The patients started active and
      passive ankle mobilization from the next day, partial weightbearing walking from
      1 week, full-load walking from 4 weeks, and double-legged heel raises from 6
      weeks after surgery. RESULTS: The range of motion recovery equal to the intact
      side averaged 3.2 weeks. Double-legged heel raises and 20 continuous single
      legged heel raise exercises were possible at an average of 6.3 weeks and 9.9
      weeks, respectively. T2-weighted magnetic resonance signal intensity recovered to
      equal that of the intact portion of the same tendon at 12 weeks. The patients
      resumed sports activities or heavy labor at an average of 14.4 weeks. The
      Achilles tendon rupture score averaged 98.3 at 24 weeks. There were no
      complications. CONCLUSION: This new Achilles tendon repair approach enables early
      mobilization exercise without costly specialized orthosis or immobilization and
      allows an early return to normal life and sports activities, reducing the
      physical and economic burden on patients.

PMID- 20044499
TI  - Pelvic fractures resulting from snowboarding.
AB  - BACKGROUND: Information regarding pelvic fractures sustained during snowboarding
      is scant. PURPOSE: To analyze the epidemiologic data, injury patterns, and types
      of pelvic fractures sustained during snowboarding. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: We analyzed the epidemiologic factors, injury
      patterns, and types of pelvic fractures in 145 patients with snowboarding-related
      pelvic fractures who were admitted to our institution from the 1998-1999 to the
      2006-2007 ski season. RESULTS: The incidence of snowboarding-related pelvic
      fractures was 0.102 per 10 000 ski lift tickets, which amounted to 2% of all
      snowboarding-related fractures (fifth most common type of fracture among all
      snowboarding-related fractures). Of the pelvic fractures, 85.5% were stable (type
      A according to the Tile classification) and 14.5% were unstable (types B and C
      according to the Tile classification). Isolated sacral fractures had the second
      highest incidence (24.1%) after pubic bone and/or ischium fractures (46.9%). A
      distinct female prevalence was seen (52.4%). Jumps and isolated falls were the
      main mechanisms of injury (80%), and the incidence of collision was significantly
      higher in the unstable group than in the stable group (P = .037). In all, 57.9%
      patients classified their skill level as "intermediate," and only 9.7% of
      patients had received professional snowboarding lessons. A total of 30 subjects
      (20.8%) had other injuries along with pelvic fractures; the patients with
      multiple injuries were significantly more frequent in the unstable group than in
      the stable group (P = .035). CONCLUSION: Pelvic fractures resulting from
      snowboarding accidents included a higher proportion with isolated sacral
      fractures in the stable group and a lower prevalence of associated injuries in
      the unstable group compared with those resulting from other causes.

PMID- 20044500
TI  - In situ forces in the anteromedial and posterolateral bundles of the anterior
      cruciate ligament under simulated functional loading conditions.
AB  - BACKGROUND: The in situ forces of the anteromedial (AM) and posterolateral
      bundles (PL) of the anterior cruciate ligament (ACL) under simulated functional
      loads such as simulated muscle loads have not been reported. These data are
      instrumental for improvement of the anatomical double-bundle ACL reconstruction.
      HYPOTHESIS: The load-sharing patterns of the 2 bundles are complementary under
      simulated muscle loads. STUDY DESIGN: Descriptive laboratory study. METHODS:
      Eight cadaveric knees in this study were sequentially studied using a robotic
      testing system. Each knee was tested under 3 external loading conditions
      including (1) a 134-N anterior tibial load; (2) combined rotational loads of 10 N
      x m of valgus and 5 N x m internal tibial torques; and (3) a 400-N quadriceps
      muscle load with the knee at 0 degrees , 15 degrees , 30 degrees , 60 degrees ,
      and 90 degrees of flexion. The in situ forces of the 2 bundles of ACL were
      determined using the principle of superposition. RESULTS: Under the anterior
      tibial load, the PL bundle carried peak loads at full extension and concurrently
      had significantly lower force than the AM bundle throughout the range of flexion
      (P <.05). Under the combined rotational loads, the PL bundle contributed to
      carrying the load between 0 degrees and 30 degrees , although less than the AM
      bundle. Under simulated muscle loads, both bundles carried loads between 0
      degrees and 30 degrees . There was no significant difference between the 2 bundle
      forces at all flexion angles (P > .05). CONCLUSION: Under externally applied
      loads, in general, the AM bundle carried a greater portion of the load at all
      flexion angles, whereas the PL bundle only shared the load at low flexion angles.
      The bundles functioned in a complementary rather than a reciprocal manner to each
      other. CLINICAL RELEVANCE: The data appear to support the concept that both
      bundles function in a complementary manner. Thus, how to re-create the 2 bundle
      functions in an ACL reconstruction should be further investigated.

PMID- 20044501
TI  - Lens exposure during brain scans using multidetector row CT scanners: methods for
      estimation of lens dose.
AB  - BACKGROUND AND PURPOSE: Some recent studies on radiation lens injuries have
      indicated much lower dose thresholds than specified by the current radiation
      protection guidelines. The purpose of this research was to measure the lens dose
      during brain CT scans with multidetector row CT and to assess methods for
      estimating the lens dose. MATERIALS AND METHODS: With 8 types of multidetector
      row CT scanners, both axial and helical scans were obtained for the head part of
      a human-shaped phantom by using normal clinical settings with the orbitomeatal
      line as the baseline. We measured the doses on both eyelids by using an RPLGD
      during whole-brain scans including the orbit with the starting point at the level
      of the inferior orbital rim. To assess the effect of the starting points on the
      lens doses, we measured the lens doses by using 2 other starting points for
      scanning (the orbitomeatal line and the superior orbital rim). RESULTS: The
      CTDIvols and the lens doses during whole-brain CT including the orbit were 50.9
      113.3 mGy and 42.6-103.5 mGy, respectively. The ratios of lens dose to CTDIvol
      were 80.6%-103.4%. The lens doses decreased as the starting points were set more
      superiorly. The lens doses during scans from the superior orbital rim were 11.8%
      20.9% of the doses during the scans from the inferior orbital rim. CONCLUSIONS:
      CTDIvol can be used to estimate the lens dose during whole-brain CT when the
      orbit is included in the scanning range.

PMID- 20044503
TI  - MR imaging of gray matter involvement in multiple sclerosis: implications for
      understanding disease pathophysiology and monitoring treatment efficacy.
AB  - Recent pathologic and MR imaging studies have challenged the classic view of MS
      as a chronic inflammatory-demyelinating condition affecting solely the WM of the
      central nervous system. Indeed, an involvement of the GM has been shown to occur
      from the early stages of the disease, to progress with time, and to be only
      moderately correlated with the extent of WM injury. In this review, we summarize
      how advances in MR imaging technology and methods of analysis are contributing to
      ameliorating the detection of focal lesions and to quantifying the extent of
      "occult" pathology and atrophy, as well as to defining the topographic
      distribution of such changes in the GM of patients with MS. These advances,
      combined with the imaging of brain reorganization occurring after tissue injury,
      should ultimately result in an improved understanding and monitoring of MS
      clinical manifestations and evolution, either natural or modified by treatment.

PMID- 20044502
TI  - Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not
      increase the risk of contrast-induced nephropathy.
AB  - BACKGROUND AND PURPOSE: Concerns have recently grown regarding the safety of
      iodinated contrast agents used for CTA and CTP imaging. We tested whether the
      incidence of AN, defined by a >or=25% increase in the post-contrast scan
      creatinine level, was higher among patients with ischemic stroke who underwent a
      functional contrast-enhanced CT protocol compared with those who had no iodinated
      contrast administration. MATERIALS AND METHODS: The contrast-exposed group
      consisted of 575 patients with acute ischemic stroke who underwent CTA (n = 313),
      CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography (n = 38)
      within 24 hours of stroke onset and were consecutively enrolled in a prospective
      cohort study. The nonexposed group consisted of 343 patients with ischemic
      stroke, consecutively admitted to the same institution, who did not receive
      iodinated contrast material. Patients were stratified by baseline eGFR. In the
      primary analysis, the Fisher exact test was used to compare the incidence of AN
      between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours
      and on a cumulative basis. A secondary analysis compared the incidence of AN in
      patients who underwent conventional angiography following CTA/CTP versus patients
      who underwent CTA/CTP only. RESULTS: The incidence of AN was 5% in the exposed
      and 10% in the nonexposed group (P = .003). Patients who underwent conventional
      angiography after contrast CT were at no greater risk of AN than patients who
      underwent CTA/CTP alone (26 patients, 5%; and 2 patients, 5%, respectively; P =
      .7). CONCLUSIONS: Administration of a contrast-enhanced CT protocol involving
      CTA/CTP and conventional angiography in selected patients does not appear to
      increase the incidence of CIN.

PMID- 20044504
TI  - Revisiting anterior atlantoaxial subluxation with overlooked information on MR
      images.
AB  - BACKGROUND AND PURPOSE: The ADI is the imaging diagnostic clue to AAA subluxation
      of the cervical spine. Some MR imaging findings other than abnormal ADI relate to
      AAA subluxation. However, their relationship is not yet clarified. The present
      study elucidates the role of MR imaging by employing these previously overlooked
      findings. MATERIALS AND METHODS: This study enrolled 40 patients with AAA
      subluxation and 20 non-AAA subluxation patients as controls. All MR imaging was
      performed with supine neutral positioning. The morphology of the dens, bilateral
      facet joints, and surrounding ligaments, as well as the alignment of the anterior
      atlantoaxial joint, the spinolaminar line, and the intramedullary signal
      intensity, were assessed. This investigation statistically analyzed the
      difference among these groups. RESULTS: Thirty-eight percent (15 of 40) of
      patients with AAA subluxation showed nAAA. There was no significant difference
      between the groups of AAA with normal and abnormal ADI except that more
      peridental pannus was seen in the latter group. More dens erosion (P = .022),
      tilting of anterior atlantoaxial joint (P = .022), peridental effusion (P <
      .001), lateral facet arthropathy (P < .001), abnormal spinolaminar line (P =
      .001), and focal myelopathy (P = .001) were observed in nAAA patients compared
      with the controls. The combination of peridental effusion, lateral facet
      arthropathy, abnormal intramedullary signals, and abnormal spinolaminar line
      showed a sensitivity of 100% and a specificity of 90% in diagnosing AAA
      subluxation. CONCLUSIONS: MR imaging provides important biomechanical clues,
      other than ADI, that improve accuracy in diagnosing atlantoaxial instability.

PMID- 20044505
TI  - Percutaneous sclerotherapy for facial venous malformations: subjective clinical
      and objective MR imaging follow-up results.
AB  - BACKGROUND AND PURPOSE: Venous malformations are the most common of all vascular
      anomalies, 40% of which are found in the head and neck. We discuss results of
      percutaneous sclerotherapy using bleomycin for facial VMs by using subjective
      clinical assessment and objective changes on MR imaging. MATERIALS AND METHODS:
      Thirty-seven patients with facial VMs were treated by percutaneous sclerotherapy
      with bleomycin. Of these, 31 patients with 32 lesions had pre- and posttreatment
      MR imaging. Each lesion received between 1 and 9 sclerotherapy sessions (average,
      3.5). MR findings and clinical results of treatment were retrospectively
      reviewed. Clinical results were based on the physician's physical examination and
      interview of the patient; these were classified as worse, unchanged, or better.
      Objective results on MR imaging were classified as worse, no change, minor
      improvement (<50% decrease in size), marked improvement (>or=50% decrease), or
      cure. Objective and subjective results were compared. RESULTS: Twenty-one lesions
      showed objective improvement on MR imaging. Of these, 10 showed minor decrease in
      size and 11 showed marked decrease. Eleven lesions showed no change on MR
      imaging. No VMs were worse or completely cured. Subjectively, 29 patients and 30
      clinicians thought that lesions improved. Four of 32 (12.5%) patients suffered
      minor transient complications. CONCLUSIONS: Percutaneous sclerotherapy by using
      bleomycin is a safe technique to objectively decrease size and subjectively
      alleviate symptoms of facial VMs. Subjective clinical improvement is not always
      associated with visual size reduction on MR imaging. Minimal size reduction or
      partial fibrosis of the lesion may be enough to achieve subjective clinical
      improvement.

PMID- 20044506
TI  - Endovascular treatment of wide-neck middle cerebral artery aneurysms with stents:
      a review of 16 cases.
AB  - BACKGROUND AND PURPOSE: MCA aneurysms are common and often pose technical
      challenges to interventionalists. Intracranial stents are widely used in treating
      wide-neck aneurysms in other locations. To evaluate the feasibility,
      effectiveness, and safety of stent placement in MCA aneurysms, we performed this
      retrospective study. MATERIALS AND METHODS: Between October 2003 and May 2009, 16
      patients with 16 wide-neck MCA aneurysms were treated with stents at our
      institution. We retrospectively collected and analyzed the data for these
      patients, including demographics, morphologic features of the aneurysms,
      treatment results, and follow-up. RESULTS: Seventeen stents, including 12
      Neuroform, 4 LEO, and 1 Enterprise, were successfully deployed in this series. Of
      the 13 aneurysms treated with stent-assisted embolization, complete occlusion was
      achieved in 9 aneurysms; residual neck remained in 1, and residual aneurysm was
      present in 3. Contrast stasis in the aneurysm sac was observed in the other 3
      aneurysms treated with stent alone. Procedure-related complication occurred in 1
      patient, leading to no permanent effect. The mRS score at discharge was 0-2 in 14
      patients and 3-6 in 2. The angiographic follow-up results of 9 patients (mean,
      5.6 months) showed that all aneurysms remained stable or improved; there was no
      in-stent stenosis, recurrence, or retreatment. The clinical follow-up (mean, 20.1
      months) demonstrated no neurologic deterioration or rebleeding. CONCLUSIONS: Our
      preliminary experience demonstrates that stent placement for the treatment of
      selected wide-neck MCA aneurysms is feasible. However, its safety and efficacy
      should be further evaluated by larger case series and more adequate follow-up.

PMID- 20044507
TI  - MR imaging of adenomas of the nonpigmented ciliary epithelium of the eye.
AB  - BACKGROUND AND PURPOSE: ANPCEs are rare benign tumors of the eye arising from the
      NPCE in adults, which may be clinically mistaken for melanoma. This study was
      undertaken to delineate clinical and MR imaging features of these tumors.
      MATERIALS AND METHODS: Clinical presentation and MR imaging findings of 8
      patients (6 women and 2 men; median age, 51 years) with pathologically confirmed
      ANPCEs were retrospectively reviewed. Location, size, shape, margin, signal
      intensity, and gadolinium-enhancement characteristics of all tumors were
      evaluated. Signal intensity and degree of enhancement were graded in comparison
      with the ipsilateral lacrimal gland. RESULTS: MR imaging revealed a circumscribed
      enhancing mass within the ciliary body of the eye in all 8 patients. The mass was
      ovoid in 6 patients and spheric in 2. Gadolinium enhancement was marked in 4
      lesions and moderate in the other 4. Both T1 and T2 relaxation times were
      qualitatively identical to those in the lacrimal gland in 2 tumors. In the
      remaining 6 tumors, the T1 was identical to and the T2 longer than that in the
      lacrimal gland. CONCLUSIONS: ANPCE should be included in the differential
      diagnosis of a spheric or ovoid enhancing ciliary body mass with T1 similar to
      that in the lacrimal gland and T2 equal to or longer than that in the lacrimal
      gland.

PMID- 20044508
TI  - Clinical experience with high-viscosity cements for percutaneous vertebral body
      augmentation: occurrence, degree, and location of cement leakage compared with
      kyphoplasty.
AB  - BACKGROUND AND PURPOSE: Vertebroplasty is known for its high leakage rate
      compared with kyphoplasty. In recent preclinical studies, high-viscosity cements
      were shown to significantly enhance the uniformity of cement filling and decrease
      the incidence of leakage in cancellous bonelike substrates compared with low
      viscosity cements. In this study, the incidence and pattern of cement leakage by
      using a new high-viscosity cement (Confidence spinal cement system) was compared
      with that of standard kyphoplasty. MATERIALS AND METHODS: Postoperative
      radiographs of patients treated with either kyphoplasty or Confidence were
      analyzed for cement leakage by using a stringent and thorough 4-point scale
      (none, minimal, moderate, or severe). When leakage was observed, the location of
      the cement leakage was also recorded and described as diskal, venous,
      paravertebral, or epidural. Sixty-two consecutive patients with 112 treated
      levels were included in this retrospective review. There were 46 kyphoplasty-
      versus 66 Confidence-treated levels, which ranged from T3 to L5. RESULTS: The
      average vertebral collapse reached 27.9 +/- 20.7% in the Confidence group versus
      25.0 +/- 19.1% in the kyphoplasty group. There was no or mild leakage in 92% of
      Confidence and 91% of the kyphoplasty cases (mild, 39% Confidence versus 50%
      kyphoplasty). Severe leakage was only reported in 1 (2%) Confidence and 1 (2%)
      kyphoplasty case. In both cases, the severe leakage was found in the disk space.
      No significant leakage that required any surgical intervention was noticed.
      CONCLUSIONS: This finding confirms prior observations that highly viscous cements
      may increase the safety of vertebral augmentation techniques compared with less
      viscous cements. The high-viscosity Confidence cement results in a leakage rate
      comparable with that of kyphoplasty.

PMID- 20044509
TI  - The intestinal lymph fistula model--a novel approach to study ghrelin secretion.
AB  - The orexigenic hormone ghrelin is secreted from the stomach and has been
      implicated in the regulation of energy and glucose homeostasis. We hypothesized
      that ghrelin, like other gastrointestinal (GI) hormones, is present in intestinal
      lymph, and sampling this compartment would provide advantages for studying
      ghrelin secretion in rodents. Blood and lymph were sampled from catheters in the
      jugular vein and mesenteric lymph duct before and after intraduodenal (ID)
      administration of isocaloric Ensure, dextrin, or Liposyn meals or an equal volume
      of saline in conscious Sprague-Dawley rats. Total ghrelin levels were measured
      using an established radioimmunoassay. Acyl and des-acyl ghrelin were measured
      using two-site ELISA. Fasting ghrelin levels in lymph were significantly higher
      than in plasma (means +/- SE: 3,307.9 +/- 272.9 vs. 2,127.1 +/- 115.0 pg/ml, P =
      0.004). Postingestive acyl and des-acyl ghrelin levels were also significantly
      higher, whereas the ratio of acyl:des-acyl ghrelin was similar in lymph and
      plasma (0.91 +/- 0.28 vs. 1.20 +/- 0.36, P = 0.76). The principle enzymes
      responsible for deacylation of ghrelin were lower in lymph than in plasma.
      Following ID Ensure, maximum ghrelin suppression occurred at 2 h in lymph
      compared with at 1 h in plasma. The return of suppressed ghrelin levels to
      baseline was also delayed in lymph. Similarly, dextrin also induced significant
      suppression of ghrelin (two-way ANOVA: P = 0.02), whereas Liposyn did not (P =
      0.32). On the basis of these findings, it appears that intestinal lymph, which
      includes drainage from the interstitium of the GI mucosa, is enriched in ghrelin.
      Despite reduced deacylating activity in lymph, there is not a disproportionate
      amount of acyl ghrelin in this pool. The postprandial dynamics of ghrelin are
      slower in lymph than plasma, but the magnitude of change is greater. Assessing
      ghrelin levels in the lymph may be advantageous for studying its secretion and
      concentrations in the gastric mucosa.

PMID- 20044510
TI  - Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat
      model by increasing the release of GLP-1.
AB  - Bile acid sequestrants have been shown to lower glucose levels in patients with
      type 2 diabetes. To investigate how colesevelam (CL) HCl improves hyperglycemia,
      studies were conducted in diet-induced obesity (F-DIO) rats, which develop
      insulin resistance when fed a high-energy (high fat/high sucrose) diet (HE). The
      rats were fed HE; HE + 2% CL; HE + 0.02% SC-435 (SC), an apical sodium-dependent
      bile acid transporter inhibitor; and regular chow (controls). After 4 wk of
      treatment, both in the HE group and the SC + HE group, plasma glucose and insulin
      levels remained elevated compared with baseline values throughout an oral glucose
      tolerance test (OGTT). In contrast, in the CL + HE group, plasma glucose levels
      returned to baseline by the end of the test, and insulin peaked in 15-30 min and
      then returned to baseline. CL induced release of glucagon-like peptide-1 (GLP-1)
      because the area under the curve of plasma total GLP-1 in the CL + HE group was
      significantly greater than in the HE group during the OGTT. Bile acid
      concentrations in the portal blood did not decrease in the HE group but declined
      significantly both in the CL + HE and SC + HE groups with reduced farnesoid X
      receptor activation compared with controls. We concluded that CL reduces plasma
      glucose levels by improving insulin resistance in this rat model. It is unlikely
      that the improvement is attributable to decreased bile acid flux to the liver but
      is likely secondary to induced GLP-1 secretion, which improves insulin release.

PMID- 20044511
TI  - Lactobacillus acidophilus stimulates the expression of SLC26A3 via a
      transcriptional mechanism.
AB  - Clinical efficacy of probiotics in treating various forms of diarrhea has been
      clearly established. However, mechanisms underlying antidiarrheal effects of
      probiotics are not completely defined. Diarrhea is caused either by decreased
      absorption or increased secretion of electrolytes and solutes in the intestine.
      In this regard, the electroneutral absorption of two major electrolytes, Na(+)
      and Cl(-), occurs mainly through the coupled operation of Na(+)/H(+) exchangers
      and Cl(-)/OH(-) exchangers. Previous studies from our laboratory have shown that
      Lactobacillus acidophilus (LA) acutely stimulated Cl(-)/OH(-) exchange activity
      via an increase in the surface levels of the apical anion exchanger SLC26A3
      (DRA). However, whether probiotics influence SLC26A3 expression and promoter
      activity has not been examined. The present studies were, therefore, undertaken
      to investigate the long-term effects of LA on SLC26A3 expression and promoter
      activity. Treatment of Caco-2 cells with LA for 6-24 h resulted in a significant
      increase in Cl(-)/OH(-) exchange activity. DRA mRNA levels were also
      significantly elevated in response to LA treatment starting as early as 8 h.
      Additionally, the promoter activity of DRA was increased by more than twofold
      following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in
      vivo studies using mice gavaged with LA also showed significantly increased DRA
      mRNA ( approximately 4-fold) and protein expression in the colonic regions as
      assessed by Western blot analysis and immunofluorescence. In conclusion, increase
      in DRA promoter activity and expression may contribute to the upregulation of
      intestinal electrolyte absorption and might underlie the potential antidiarrheal
      effects of LA.

PMID- 20044512
TI  - Iodinated contrast opacification gradients in normal coronary arteries imaged
      with prospectively ECG-gated single heart beat 320-detector row computed
      tomography.
AB  - BACKGROUND: To define and evaluate coronary contrast opacification gradients
      using prospectively ECG-gated single heart beat 320-detector row coronary
      angiography (CTA). METHODS AND RESULTS: Thirty-six patients with normal coronary
      arteries determined by 320 x 0.5-mm detector row coronary CTA were
      retrospectively evaluated with customized image postprocessing software to
      measure Hounsfield Units at 1-mm intervals orthogonal to the artery center line.
      Linear regression determined correlation between mean Hounsfield Units and
      distance from the coronary ostium (regression slope defined as the distance
      gradient G(d)), lumen cross-sectional area (G(a)), and lumen short-axis diameter
      (G(s)). For each gradient, differences between the 3 coronary arteries were
      analyzed with ANOVA. Linear regression determined correlations between measured
      gradients, heart rate, body mass index, and cardiac phase. To determine
      feasibility in lesions, all 3 gradients were evaluated in 22 consecutive patients
      with left anterior descending artery lesions > or =50% stenosis. For all 3
      coronary arteries in all patients, the gradients G(a) and G(s) were significantly
      different from zero (P<0.0001), highly linear (Pearson r values, 0.77 to 0.84),
      and had no significant difference between the left anterior descending, left
      circumflex, and right coronary arteries (P>0.503). The distance gradient G(d)
      demonstrated nonlinearities in a small number of vessels and was significantly
      smaller in the right coronary artery when compared with the left coronary system
      (P<0.001). Gradient variations between cardiac phases, heart rates, body mass
      index, and readers were low. Gradients in patients with lesions were
      significantly different (P<0.021) than in patients considered normal by CTA.
      CONCLUSIONS: Measurement of contrast opacification gradients from temporally
      uniform coronary CTA demonstrates feasibility and reproducibility in patients
      with normal coronary arteries. For all patients, the gradients defined with
      respect to the coronary lumen cross-sectional area and short-axis diameters are
      highly linear, not significantly influenced by the coronary artery (left anterior
      descending artery versus left circumflex versus right coronary artery), and have
      only small variation with respect to patient parameters. Preliminary evaluation
      of gradients across coronary artery lesions is promising but requires additional
      study.

PMID- 20044513
TI  - Vasoreactive response to maternal hyperoxygenation in the fetus with hypoplastic
      left heart syndrome.
AB  - BACKGROUND: Cardiopulmonary interactions play an important role in the
      pathophysiology of hypoplastic left heart syndrome (HLHS). Pulmonary vasculopathy
      has been identified, especially in those with restrictive/intact atrial septum.
      Responsiveness of the pulmonary vasculature to maternal hyperoxygenation (MH) may
      provide a tool to assess the degree of pulmonary vasculopathy present before
      birth. METHODS AND RESULTS: Doppler echocardiography was performed in 27 normal
      and 43 HLHS fetuses. In HLHS, sampling was repeated after 10 minutes of MH with
      60% FiO(2) and after 5 minutes of recovery. Sampling was performed in the
      proximal, midportion, and distal branch pulmonary artery (PA). Pulsatility index
      (PI) was used as a measure of vascular impedance. Of the HLHS fetuses, 34 had an
      open interatrial septum and 9 had a restrictive/intact atrial septum. At birth, 5
      fetuses underwent immediate intervention on the interatrial septum. Middle
      cerebral artery PI was lower in HLHS versus normal fetuses (P<0.001). There was
      no difference in UA, DA, or branch PA PI between normal fetuses and those with
      HLHS. MH led to a significant decrease in PI at each of the PA sites sampled in
      fetuses with an open atrial septum (P<0.001); however, there no was significant
      change in the PI in fetuses that required immediate intervention on the atrial
      septum at birth. Using a cutoff value of <10% vasoreactivity, the sensitivity of
      MH testing for determining need for immediate intervention at birth is 100% (0.46
      to 1.0); specificity, 94% (0.78 to 0.99); positive predictive value, 71% (0.30 to
      0.95); and negative predictive value, 100% (0.86 to 1.0). No untoward effects
      were seen with MH. CONCLUSIONS: PA vasoreactivity to MH occurs in the fetus with
      HLHS. MH testing accurately identifies fetuses requiring urgent postnatal
      intervention at birth and may be used to select candidates for fetal atrial
      septoplasty.

PMID- 20044514
TI  - Noninvasive assessment of murine pulmonary arterial pressure: validation and
      application to models of pulmonary hypertension.
AB  - BACKGROUND: Genetically modified mice offer the unique opportunity to gain
      insight into the pathophysiology of pulmonary arterial hypertension. In mice,
      right heart catheterization is the only available technique to measure right
      ventricular systolic pressure (RVSP). However, it is a terminal procedure and
      does not allow for serial measurements. Our objective was to validate a
      noninvasive technique to assess RVSP in mice. METHODS AND RESULTS: Right
      ventricle catheterization and echocardiography (30-MHz transducer) were
      simultaneously performed in mice with pulmonary hypertension induced acutely by
      infusion of a thromboxane analogue, U-46619, or chronically by lung-specific
      overexpression of interleukin-6. Pulmonary acceleration time (PAT) and ejection
      time (ET) were measured in the parasternal short-axis view by pulsed-wave Doppler
      of pulmonary artery flow. Infusion of U-46619 acutely increased RVSP, shortened
      PAT, and decreased PAT/ET. The pulmonary flow pattern changed from symmetrical at
      baseline to asymmetrical at higher RVSPs. In wild-type and interleukin-6
      overexpressing mice, the PAT correlated linearly with RVSP (r(2)=-0.67,
      P<0.0001), as did PAT/ET (r(2)=-0.76, P<0.0001). Sensitivity and specificity for
      detecting high RVSP (>32 mm Hg) were 100% (7/7) and 86% (6/7), respectively, for
      both indices (cutoff values: PAT, <21 ms; PAT/ET, <39%). Intraobserver and
      interobserver variability of PAT and PAT/ET were <6%. CONCLUSIONS: Right
      ventricular systolic pressure can be estimated noninvasively in mice.
      Echocardiography is able to detect acute and chronic increases in RVSP with high
      sensitivity and specificity as well as to assess the effects of treatment on
      RVSP. This noninvasive technique may permit the characterization of the evolution
      of pulmonary arterial hypertension in genetically modified mice.

PMID- 20044515
TI  - Intracellular Ca2+ silences L-type Ca2+ channels in mesenteric veins: mechanism
      of venous smooth muscle resistance to calcium channel blockers.
AB  - RATIONALE: Calcium channel blockers (CCBs) exert their antihypertensive effect by
      reducing cardiac afterload but not preload, suggesting that Ca(2+) influx through
      L-type Ca(2+) channels (LTCC) mediates arterial but not venous tone. OBJECTIVE:
      The object of this study was to resolve the mechanism of venous resistance to
      CCBs. METHODS AND RESULTS: We compared the sensitivity of depolarization (KCl)
      induced constriction of rat small mesenteric arteries (MAs) and veins (MVs) to
      the dilator effect of CCBs. Initial findings confirmed that nifedipine
      progressively dilated depolarization-induced constrictions in MAs but not MVs.
      However, Western blots showed a similar expression of the alpha(1C) pore-forming
      subunit of the LTCC in both vessels. Patch-clamp studies revealed a similar
      density of whole-cell Ca(2+) channel current between single smooth muscle cells
      (SMCs) of MAs and MVs. Based on these findings, we hypothesized that LTCCs are
      expressed but "silenced" by intracellular Ca(2+) in venous SMCs. After depletion
      of intracellular Ca(2+) stores by the SERCA pump inhibitor thapsigargin,
      depolarization-induced constrictions in MVs were blocked 80% by nifedipine
      suggesting restoration of Ca(2+) influx through LTCCs. Similarly, KCl-induced
      constrictions were sensitive to block by nifedipine after depletion of
      intracellular Ca(2+) stores by caffeine, ryanodine, or 2-aminoethoxydiphenyl
      borate. Cell-attached patch recordings of unitary LTCC currents confirmed rare
      channel openings during depolarization of venous compared to arterial SMCs, but
      chelating intracellular Ca(2+) significantly increased the open-state probability
      of venous LTCCs. CONCLUSIONS: We report that intracellular Ca(2+) inactivates
      LTCCs in venous SMCs to confer venous resistance to CCB-induced dilation, a
      fundamental drug property that was previously unexplained.

PMID- 20044516
TI  - A common MLP (muscle LIM protein) variant is associated with cardiomyopathy.
AB  - RATIONALE: We previously discovered the human 10T-->C (Trp4Arg) missense mutation
      in exon 2 of the muscle LIM protein (MLP, CSRP3) gene. OBJECTIVE: We sought to
      study the effects of this single-nucleotide polymorphism in the in vivo
      situation. METHODS AND RESULTS: We now report the generation and detailed
      analysis of the corresponding Mlp(W4R/+) and Mlp(W4R/W4R) knock-in animals, which
      develop an age- and gene dosage-dependent hypertrophic cardiomyopathy and heart
      failure phenotype, characterized by almost complete loss of contractile reserve
      under catecholamine induced stress. In addition, evidence for skeletal muscle
      pathology, which might have implications for human mutation carriers, was
      observed. Importantly, we found significantly reduced MLP mRNA and MLP protein
      expression levels in hearts of heterozygous and homozygous W4R-MLP knock-in
      animals. We also detected a weaker in vitro interaction of telethonin with W4R
      MLP than with wild-type MLP. These alterations may contribute to an increased
      nuclear localization of W4R-MLP, which was observed by immunohistochemistry.
      CONCLUSIONS: Given the well-known high frequency of this mutation in Caucasians
      of up to 1%, our data suggest that (W4R-MLP) might contribute significantly to
      human cardiovascular disease.

PMID- 20044517
TI  - Incidence of newly detected atrial arrhythmias via implantable devices in
      patients with a history of thromboembolic events.
AB  - BACKGROUND AND PURPOSE: Evidence of atrial tachycardia/atrial fibrillation
      (AT/AF) is often sought in patients with ischemic stroke or transient ischemic
      attack. We studied patients with previous thromboembolic events (TE) who were
      implanted with devices capable of continuous arrhythmia monitoring to
      comprehensively quantify the incidence and duration of newly detected AT/AF.
      METHODS: This study represents a subgroup analysis of the TRENDS trial, which
      included patients with clinical indications for pacemakers or defibrillators and
      >or=1 stroke risk factors (heart failure, hypertension, age 65 or older,
      diabetes, or previous TE). A history of AF was not required. All implanted
      devices were capable of continuously monitoring the cumulative time spent in
      AT/AF each day. This analysis focuses primarily on the incidence and duration of
      newly detected AT/AF (defined as >or=5 minutes of AT/AF on any day) in patients
      with previous TE, no documented history of AF, and no warfarin or antiarrhythmic
      drug use. RESULTS: A total of 319 patients had a history of TE and >or=1 day of
      device data. Patients with a documented history of AF (n=80), warfarin use
      (n=56), or antiarrhythmic drug use (n=20) were excluded from analysis. Of the
      remaining 163 patients, newly detected AT/AF was identified via the device in 45
      patients (28%) over a mean follow-up of 1.1+/-0.7 years. AT/AF recurred
      infrequently, with only 12 patients experiencing AT/AF on >10% of follow-up days.
      CONCLUSIONS: Newly detected episodes of AT/AF were found via continuous
      monitoring in 28% of patients with previous TE. Most episodes would not have been
      detected by standard intermittent monitoring techniques.

PMID- 20044518
TI  - Factors explaining excess stroke prevalence: the Spanish stroke belt.

PMID- 20044519
TI  - Downregulation of potassium chloride cotransporter KCC2 after transient focal
      cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: The potassium chloride cotransporter 2 (KCC2) is the main
      neuronal chloride extruder in the adult nervous system. Therefore, KCC2 is
      responsible for an inwardly directed electrochemical gradient of chloride that
      leads to hyperpolarizing GABA-mediated responses. Under some pathophysiological
      conditions, GABA has been reported to be depolarizing because of a downregulation
      of KCC2. This is the first study to our knowledge analyzing the expression of
      KCC2 after a focal cerebral ischemia. METHODS: Mild and severe ischemia were
      induced in rats by a transient occlusion of the middle cerebral artery for 30 and
      120 minutes, respectively. KCC2 mRNA and protein expression were studied in the
      ischemic hemisphere after different reperfusion times (2 hour, 1 day, 7 days, 30
      days, 168 days) by using quantitative polymerase chain reaction, Western
      blotting, and immunohistological staining. RESULTS: We found a substantial
      decrease of KCC2 mRNA and protein levels in the ischemic hemisphere, with a
      stronger downregulation of KCC2 after severe vs mild ischemia. Long-term
      surviving cells expressing KCC2 could be detected in the infarct core. These
      cells were identified as GABAergic interneurons mainly expressing parvalbumin.
      CONCLUSIONS: Our study revealed a substantial neuron-specific downregulation of
      KCC2 after focal cerebral ischemia.

PMID- 20044520
TI  - Ischemia in broca area is associated with broca aphasia more reliably in acute
      than in chronic stroke.
AB  - BACKGROUND AND PURPOSE: We aimed to determine if ischemia involving Broca area
      predicts Broca aphasia more reliably in acute or chronic stroke. METHODS: We
      included consecutive right-hand-dominant patients with left hemisphere ischemic
      stroke (<48 hours from onset for acute stroke or >6 months after stroke for
      chronic stroke). MRI scans were analyzed for ischemic lesions or hypoperfusion in
      Broca area (Brodmann areas 44 and 45). Patients were scored on the Western
      Aphasia Battery to classify aphasia syndromes; chi(2) tests were used to identify
      significant associations. RESULTS: The presence of infarct involving any part of
      Broca area and the presence of Broca or global aphasia was much stronger in acute
      (chi(2)=38.1; df1; P<0.0001) than in chronic stroke (chi(2)=0.54; df1; P=0.46;
      not significant). The association between infarct or hypoperfusion covering all
      of Broca area and the presence of Broca or global aphasia was much stronger in
      acute (chi(2)=35.8; df1; P<0.0001) than in chronic stroke (chi(2)=1.2; df1;
      p=0.27; not significant). In a subset of 20 patients studied longitudinally, the
      associations were significant only acutely, not chronically (chi(2)=20; df1;
      P<0.0001 vs. chi(2)=0; df1; p=1; not significant for ischemia involving part of
      Broca area, and chi(2)=16.4; df1; P<0.0001 vs chi(2)=3.2; df1; p=0.08; not
      significant for ischemia covering all of Broca area). CONCLUSIONS: Broca aphasia
      is more reliably associated with infarct/ hypoperfusion of Broca area in acute
      stroke. Many chronic stroke patients with damage to part or all of Broca area had
      neither Broca nor global aphasia. Broca or global aphasia was sometimes present
      initially in these patients but resolved by 6 months. Our results indicate that
      the acute aphasia syndrome may allow the clinician to predict the compromised
      vascular territory, even when structural imaging shows only a small (or no)
      infarct.

PMID- 20044521
TI  - Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic
      time window and optimal duration.
AB  - BACKGROUND AND PURPOSE: Deferoxamine (DFX) reduces brain edema, neurological
      deficits, and brain atrophy after intracerebral hemorrhage (ICH) in aged and
      young rats. Our previous study found that 50 mg/kg is an effective dose in aged
      rats. In the present study, we explored potential therapeutic time windows and
      optimal therapeutic durations. METHODS: Aged male Fischer 344 rats (18 months
      old) sustained an intracaudate injection of 100 microL autologous whole blood,
      followed by intramuscular DFX or vehicle beginning at different time points, or
      continuing for different durations. Subgroups of rats were euthanized at day 3
      for brain edema measurement and day 56 for brain atrophy determination.
      Behavioral tests were performed on days 1, 28, and 56 after ICH. RESULTS:
      Systemic administration of DFX, when begun within 12 hours after ICH, reduced
      brain edema. DFX treatment started 2 hours after ICH and administered for >or=7
      days attenuated ICH-induced ventricle enlargement, caudate atrophy, and
      neurological deficits. DFX attenuated ICH-induced brain atrophy and neurological
      deficits without detectable side effects when begun within 24 hours and
      administered for 7 days. CONCLUSIONS: To the extent that these results can be
      translated to humans, the therapeutic time window and the optimal duration for
      DFX in this aged rat model of ICH may provide useful information for an ongoing
      DFX-ICH clinical trial.

PMID- 20044522
TI  - Length of stay and total hospital charges of clipping versus coiling for ruptured
      and unruptured adult cerebral aneurysms in the Nationwide Inpatient Sample
      database 2002 to 2006.
AB  - BACKGROUND AND PURPOSE: We have previously reported the difference in length of
      stay and hospital charges for patients with cerebral aneurysms treated with
      either clipping or coiling at our institution. We now report an analysis of the
      same comparison at a national level conducted using the Nationwide Inpatient
      Sample database. METHODS: We obtained the Nationwide Inpatient Sample from the
      Healthcare Cost and Utilization Project, Agency for Healthcare Quality and
      Research. The Nationwide Inpatient Sample is the largest all-payer inpatient care
      database in the US and represents approximately 20% of all inpatient admissions
      to US nonfederal hospitals. Hospitalizations for clipping or coiling of ruptured
      and unruptured cerebral aneurysms from 2002 to 2006 were identified by cross
      matching International Classification of Diseases-9 codes for diagnoses of
      subarachnoid hemorrhage (430) or unruptured cerebral aneurysm (437.3) with
      procedure codes for clipping (39.51) or coiling (39.79, 39.72, or 39.52) of
      cerebral aneurysms. Length of hospital stay and total hospital charges for
      clipping and coiling were compared using linear mixed models adjusted for the
      following patient and hospital-specific factors: gender, age, race/ethnicity,
      admission source and type, median income level in patient's postal code of
      residence, payer for care, comorbidities, and hospital cerebral aneurysm case
      volume, bed size, teaching status, rural/urban location, and geographic region.
      RESULTS: There were 9635 hospitalizations for ruptured aneurysm treatments (6019
      clipping, 3616 coiling) and 9399 hospitalizations for unruptured aneurysm
      treatments (4700 clipping, 4699 coiling). For ruptured aneurysm patients, after
      adjusting for the effects of patient-specific and hospital-specific factors,
      clipping compared to coiling was associated with significantly longer length of
      stay (P<0.0001) and significantly higher total hospital charges (P<0.0001). For
      unruptured aneurysm patients, clipping compared to coiling was associated with
      significantly longer length of stay (P<0.0001) and significantly higher total
      hospital charges (P<0.0001). After adjusting for the effects of hospital-level
      and patient-level characteristics, clipping as compared to coiling was associated
      with an average of 1.2-times more days in hospitalization for ruptured patients
      and was associated with an average of 1.8-times more days in hospitalization for
      unruptured patients. On average, clipping resulted in $15,325 more in total
      charge for ruptured patients and resulted in $11,263 more in total charge for
      unruptured patients after considering all relevant hospital and patient
      characteristics. CONCLUSIONS: The results of this nationwide analysis differed
      from the findings of our single institution study. Clipping compared to coiling
      was associated with significantly longer lengths of stay and significantly higher
      total hospital charges for both ruptured and unruptured aneurysm patients.

PMID- 20044524
TI  - An age old question: does size really matter?

PMID- 20044523
TI  - Genome-wide association studies of MRI-defined brain infarcts: meta-analysis from
      the CHARGE Consortium.
AB  - BACKGROUND AND PURPOSE: Previous studies examining genetic associations with MRI
      defined brain infarct have yielded inconsistent findings. We investigated genetic
      variation underlying covert MRI infarct in persons without histories of transient
      ischemic attack or stroke. We performed meta-analysis of genome-wide association
      studies of white participants in 6 studies comprising the Cohorts for Heart and
      Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Using 2.2
      million genotyped and imputed single nucleotide polymorphisms, each study
      performed cross-sectional genome-wide association analysis of MRI infarct using
      age- and sex-adjusted logistic regression models. Study-specific findings were
      combined in an inverse-variance-weighted meta-analysis, including 9401
      participants with mean age 69.7 (19.4% of whom had >or=1 MRI infarct). RESULTS:
      The most significant association was found with rs2208454 (minor allele
      frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the
      downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each
      copy of the minor allele was associated with lower risk of MRI infarcts (odds
      ratio, 0.76; 95% confidence interval, 0.68-0.84; P=4.64x10(-7)). Highly
      suggestive associations (P<1.0x10(-5)) were also found for 22 other single
      nucleotide polymorphisms in linkage disequilibrium (r(2)>0.64) with rs2208454.
      The association with rs2208454 did not replicate in independent samples of 1822
      white and 644 black participants, although 4 single nucleotide polymorphisms
      within 200 kb from rs2208454 were associated with MRI infarcts in the black
      population sample. CONCLUSIONS: This first community-based, genome-wide
      association study on covert MRI infarcts uncovered novel associations. Although
      replication of the association with top single nucleotide polymorphisms failed,
      possibly because of insufficient power, results in the black population sample
      are encouraging, and further efforts at replication are needed.

PMID- 20044525
TI  - gamma-Glutamyltranspeptidase and incident stroke among Japanese men and women:
      the Circulatory Risk in Communities Study (CIRCS).
AB  - BACKGROUND AND PURPOSE: Although serum gamma-glutamyltranspeptidase (GGT) levels
      have been associated with cardiovascular disease incidence, few studies have
      taken into account the effect of alcohol intake on GGT levels. In this study, we
      examined the relationship between GGT and stroke incidence according to drinking
      status. METHODS: We conducted a prospective cohort study of Japanese women
      (N=6281) and men (N=3471) aged 40 to 69 years living in communities under
      systematic surveillance for stroke incidence. RESULTS: During the 18-year follow
      up, 202 (3.2%) women and 230 (6.6%) men had strokes. Serum GGT levels were
      positively associated with risk of total stroke for women but not men. The
      multivariable hazard ratios of total stroke for the highest quartile of GGT
      compared with the lowest quartile were 1.56 (95% CI, 1.01 to 2.39) for women and
      1.37 (95% CI, 0.89 to 2.11) for men. Moreover, GGT was associated with total and
      ischemic stroke risks for never-drinking women. CONCLUSIONS: Serum GGT is
      associated with risk of total and ischemic strokes for Japanese women, especially
      never-drinkers.

PMID- 20044526
TI  - Intima-media thickness and regional cerebral blood flow in older adults.
AB  - BACKGROUND AND PURPOSE: The relationship between the thickness of the carotid
      intima (IMT) and brain function remains unclear in those without clinical
      manifestations of cerebrovascular disease. Understanding the neural correlates of
      this vascular measure is important in view of emerging evidence linking poorer
      cognitive performance with increased IMT in individuals without clinical
      cerebrovascular disease. METHODS: Seventy-three participants in the Baltimore
      Longitudinal Study of Aging (70.9 years; SD, 7.3) were evaluated with carotid
      artery ultrasound and resting [(15)O]H(2)O positron emission tomography. RESULTS:
      After adjusting for age, gender, and gray and white matter volumes in the regions
      where IMT is related to regional cerebral blood flow (rCBF), we found that higher
      IMT was associated with lower rCBF in lingual, inferior occipital, and superior
      temporal regions. Higher IMT was also associated with higher rCBF in medial
      frontal gyrus, putamen, and hippocampal-uncal regions (P=0.001). Whereas women
      had lower IMT (P=0.01) and mean arterial pressure (P=0.05) than men, they showed
      more robust associations between IMT and rCBF. The relationship between IMT and
      rCBF was only minimally affected by additional adjustment for mean arterial
      pressure. CONCLUSIONS: IMT is related to patterns of resting rCBF in older adults
      without clinical manifestations of cerebrovascular disease, suggesting that there
      are regional differences in CBF that are associated with subclinical vascular
      disease.

PMID- 20044527
TI  - Prevalence of embolic signals in acute coronary syndromes.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to assess the prevalence of
      embolic signals (ES) in acute coronary syndromes (ACS) and their association with
      stroke. METHODS: From December 2004 to October 2006, 209 consecutive patients
      with ACS (without prosthetic heart valves or previous stroke) were studied within
      72 hours of symptom onset. Patients underwent ES monitoring in both middle
      cerebral arteries by transcranial Doppler for 30 minutes. Median follow-up was 14
      months after discharge. RESULTS: Patients were treated according to current
      European Society Cardiology guidelines. Specifically, 92% of patients received
      heparin(s), 100% aspirin, 92% clopidogrel, 67% intravenous glycoprotein IIb/IIIa
      inhibitors, 9% fibrinolysis, and 67% underwent angioplasty. ES were detected in 7
      patients (prevalence 3.4%; 95% CI, 1.4 to 6.8). Except for a higher prevalence of
      ES in patients with unstable angina versus other ACS categories (8.5% versus
      1.9%, P=0.047), none of the factors among baseline characteristics, clinical
      features, ACS treatment, and cardiac findings were associated with the presence
      of ES. During hospitalization, 3 patients without ES had cerebrovascular events
      (one stroke and 2 transient ischemic attacks), whereas no cerebrovascular events
      occurred in patients with ES. CONCLUSIONS: The prevalence of ES among
      hospitalized patients with ACS is currently low, possibly because of improvement
      in ACS treatment. In this ACS sample, ES did not appear associated with short
      term risk of cerebrovascular events.

PMID- 20044528
TI  - Counting cavitating lacunes underestimates the burden of lacunar infarction.
AB  - BACKGROUND AND PURPOSE: On brain imaging, lacunes, or cerebrospinal fluid
      containing cavities, are common and are often counted in epidemiological studies
      as old lacunar infarcts. The proportion of symptomatic lacunar infarcts that
      progress to lacunes is unknown. Noncavitating lacunar infarcts may continue to
      resemble white matter lesions. METHODS: We identified patients with acute lacunar
      stroke, with or without an acute lacunar infarct on computed tomography or MRI,
      who had follow-up imaging. A neuroradiologist classified lacunar infarcts
      progressing to definite or possible cavities on follow-up imaging. We tested
      associations between cavitation and patient-related, stroke-related, and imaging
      related features, including other features of small vessel disease. RESULTS:
      Among 90 patients (mean age 67 years), any cavitation was present on follow-up
      imaging in 25 (28%), and definite cavitation in 18 (20%). Definite cavitation was
      associated with increasing time to follow-up imaging (median 228 days, range 54
      to 1722, versus no cavitation 72 days, range 6 to 1440; P=0.0003) and deep
      cerebral atrophy (P=0.03) but not with age, stroke severity, larger initial
      infarct size, or other features of small vessel disease. Hypertension and
      diabetes were negatively associated with cavitation (P=0.01 and 0.02,
      respectively). CONCLUSIONS: Definite cavitation occurs in one fifth of
      symptomatic lacunar ischemic strokes, implying that most continue to resemble
      white matter lesions. Epidemiology and pathophysiology studies of lacunar stroke,
      which have only counted lacunes as lacunar infarcts, may have substantially
      underestimated by as much as 5 times the true burden of lacunar stroke disease.

PMID- 20044529
TI  - Limits to international estimates of stroke costs.

PMID- 20044530
TI  - Effects of perindopril-based lowering of blood pressure on intracerebral
      hemorrhage related to amyloid angiopathy: the PROGRESS trial.
AB  - BACKGROUND AND PURPOSE: Patients with cerebral amyloid angiopathy (CAA) are at
      high risk for intracerebral hemorrhage (ICH), but no effective prevention
      strategies have been established. The objective is to determine whether lowering
      of blood pressure (BP) provides protection for this high-risk patient group.
      METHODS: This study is a subsidiary analysis of the PROGRESS trial-a randomized,
      placebo-controlled trial that established the beneficial effects of BP lowering
      in patients with cerebrovascular disease; 6105 patients were randomly assigned to
      either active treatment (perindopril for all participants plus indapamide for
      those with neither an indication for nor a contraindication to a diuretic) or
      matching placebo. Outcomes were probable CAA-related ICH as defined by the Boston
      criteria, probable hypertension-related ICH, and unclassified ICH. RESULTS: Over
      a mean follow-up of 3.9 years, 16 probable CAA-related ICH, 51 probable
      hypertension-related ICH, and 44 unclassified ICH occurred. Active treatment
      reduced the risk of CAA-related ICH by 77% (95% CI, 19%-93%), that of
      hypertension-related ICH by 46% (95% CI, 4%-69%), and that of unclassified ICH by
      43% (95% CI, -5%-69%). There was no evidence of differences in the magnitude of
      the effects of treatment among different types of ICH (P homogeneity=0.4).
      CONCLUSIONS: BP-lowering treatment is likely to provide protection against all
      types of ICH.

PMID- 20044531
TI  - Safety and efficacy of ultrasound-enhanced thrombolysis: a comprehensive review
      and meta-analysis of randomized and nonrandomized studies.
AB  - BACKGROUND AND PURPOSE: Ultrasound-enhanced thrombolysis is a promising new
      approach to facilitate reperfusion therapies for acute ischemic stroke. So far, 3
      different ultrasound technologies were used to increase the thrombolytic activity
      of tissue plasminogen activator (tPA), including transcranial Doppler (TCD),
      transcranial color-coded duplex (TCCD), and low-frequency ultrasound. We
      performed a meta-analysis to evaluate the safety and efficacy of ultrasound
      enhanced thrombolysis compared to the current standard of care (intravenous tPA).
      SUBJECTS AND METHODS: Through Medline, Embase, and Cochrane database search, we
      identified and abstracted all studies of ultrasound-enhanced thrombolysis in
      acute cerebral ischemia. Principal investigators were contacted if data not
      available through peer-reviewed publication were needed. Symptomatic
      intracerebral hemorrhage (sICH) and recanalization rates were compared between
      tPA, tPA+TCD+/-microspheres (microS), tPA+TCCD+/-microS, and tPA+low-frequency
      ultrasound. RESULTS: A total of 6 randomized (n=224) and 3 nonrandomized (n=192)
      studies were identified. The rates of symptomatic intracerebral hemorrhage in
      randomized studies were as follows: tPA+TCD, 3.8% (95% CI, 0%-11.2%); tPA+TCCD,
      11.1% (95% CI, 0%-28.9%); tPA+low-frequency ultrasound, 35.7% (95% CI, 16.2%-
      61.4%); and tPA alone, 2.9% (95% CI, 0%-8.4%). Complete recanalization rates were
      higher in patients receiving combination of TCD with tPA 37.2% (95% CI, 26.5%-
      47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%-24.9%).
      In 8 trials of high-frequency (TCD/TCCD) ultrasound-enhanced thrombolysis,
      tPA+TCD/TCCD+/-microS was associated with a higher likelihood of complete
      recanalization (pooled OR, 2.99; 95% CI, 1.70-5.25; P=0.0001) when compared to
      tPA alone. High-frequency ultrasound-enhanced thrombolysis was not associated
      with an increased risk of symptomatic intracerebral hemorrhage (pooled OR, 1.26;
      95% CI, 0.44-3.60; P=0.67). CONCLUSIONS: The present safety and signal-of
      efficacy data of high-frequency ultrasound-enhanced thrombolysis should be taken
      into account in the design of future randomized controlled trials.

PMID- 20044532
TI  - Caffeinol at the receptor level: anti-ischemic effect of N-methyl-D-aspartate
      receptor blockade is potentiated by caffeine.
AB  - BACKGROUND AND PURPOSE: Although caffeinol (a combination of a low dose of
      caffeine and ethanol) was shown to robustly reduce stroke damage in experimental
      models and is now in clinical evaluation for treatment of ischemic stroke, little
      is known about the potential mechanism of its action. METHODS: We used an in vivo
      excitotoxicity model based on intracortical infusion of N-methyl-D-aspartate
      (NMDA) and a model of reversible focal ischemia to demonstrate NMDA receptor
      inhibition as a potential mechanism of caffeinol anti-ischemic activity. RESULTS:
      Caffeinol reduced the size of excitotoxic lesion, and substitution of ethanol in
      caffeinol with the NMDA antagonists CNS-1102 and MK-801 but not with MgSO(4)
      produced treatment with strong synergistic effect that was at least as robust in
      reducing ischemic damage as caffeinol. This NMDA receptor antagonist and caffeine
      combination demonstrated a long window of opportunity, activity in spontaneously
      hypertensive rats, and, unlike caffeinol, was fully effective in animals
      chronically pretreated with ethanol. CONCLUSIONS: Our study suggests that
      antiexcitotoxic properties may underlie some of the anti-ischemic effect of
      caffeinol. This study provides strong evidence that the anti-ischemic effect of
      NMDA receptor blockers in general can be dramatically augmented by caffeine, thus
      opening a possibility for new use of NMDA-based pharmacology in the treatment of
      stroke.

PMID- 20044533
TI  - Gene expression profiles in human ruptured and unruptured intracranial aneurysms:
      what is the role of inflammation?
AB  - BACKGROUND AND PURPOSE: Mechanisms underlying development and rupture of
      intracranial aneurysms (IA) are poorly recognized. The majority of studies on
      human tissue have focused on predefined pathways. We sought to analyze global
      gene expression patterns of ruptured IA, unruptured IA, and control vessels.
      METHODS: Transcription profiles were studied in human ruptured (n=8) and
      unruptured (n=6) IA, as well as in control intracranial arteries (n=5), using
      oligonucleotide microarrays. Real-time reverse-transcription polymerase chain
      reaction was used for confirmation. Functional analysis for determination of over
      represented ontological groups among gene expression profiles was also performed.
      RESULTS: The expression of 159 genes differed among the studied groups. Compared
      to the controls, 131 genes showed common directions of change in both IA groups.
      The most impacted biological processes for IA are: (1) the muscle system; (2)
      cell adhesion (downregulation); and (3) the immune system and inflammatory
      response (upregulation). Ruptured and unruptured IA differed in genes involved in
      immune/inflammatory processes; expression was reduced in ruptured IA.
      CONCLUSIONS: Decreased expression of genes related to muscle system and cell
      adhesion is important for the development of IA. The role of immune/inflammatory
      processes is unclear. Inflammation may participate in the healing process within
      IA while playing a protective role against IA rupture.

PMID- 20044534
TI  - Effects of early intensive blood pressure-lowering treatment on the growth of
      hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive
      Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT).
AB  - BACKGROUND AND PURPOSE: The Intensive Blood Pressure Reduction In Acute Cerebral
      Haemorrhage Trial (INTERACT) study suggests that early intensive blood pressure
      (BP) lowering can attenuate hematoma growth at 24 hours after intracerebral
      hemorrhage. The present analyses aimed to determine the effects of treatment on
      hematoma and perihematomal edema over 72 hours. METHODS: INTERACT included 404
      patients with CT-confirmed intracerebral hemorrhage, elevated systolic BP (150 to
      220 mm Hg), and capacity to start BP-lowering treatment within 6 hours of
      intracerebral hemorrhage. Patients were randomly assigned to an intensive (target
      systolic BP 140 mmHg) or standard guideline-based management of BP (target
      systolic BP 180 mm Hg) using routine intravenous agents. Baseline and repeat CTs
      (24 and 72 hours) were performed using standardized techniques with digital
      images analyzed centrally. Outcomes were increases in hematoma and perihematomal
      edema volumes over 72 hours. RESULTS: Overall, 296 patients had all 3 CT scans
      available for the hematoma and 270 for the edema analyses. Mean systolic BP was
      11.7 mm Hg lower in the intensive group than in the guideline group during 1 to
      24 hours. Adjusted mean absolute increases in hematoma volumes (mL) at 24 and 72
      hours were 2.40 and 0.15 in the guideline group compared with -0.74 and -2.31 in
      the intensive group, respectively, an overall difference of 2.80 (95% CI, 1.04 to
      4.56; P=0.002). Adjusted mean absolute increases in edema volumes (mL) at 24 and
      72 hours were 6.27 and 10.02 in the guideline group compared with 4.19 and 7.34
      in the intensive group, respectively, for an overall difference of 2.38 (95% CI, 
      0.45 to 5.22; P=0.10). CONCLUSIONS: Early intensive BP-lowering treatment
      attenuated hematoma growth over 72 hours in intracerebral hemorrhage. There were
      no appreciable effects on perihematomal edema.

PMID- 20044535
TI  - Four-fold increase in direct costs of stroke survivors with spasticity compared
      with stroke survivors without spasticity: the first year after the event.
AB  - BACKGROUND AND PURPOSE: The prevalence of spasticity after first-ever stroke is
      approximately 20%, but there are no health economic studies on costs associated
      with spasticity after stroke. The objective of our study was to estimate direct
      costs of stroke with spasticity for patients surviving up to 1 year after the
      stroke event in comparison to costs of stroke without spasticity. METHODS: A
      representative sample of patients with first-ever stroke hospitalized at Uppsala
      University Hospital was eligible for our cross-sectional survey. All direct costs
      during 1 year were identified for each patient, including costs for
      hospitalization (acute and rehabilitation), primary health care, medication, and
      costs for municipality services. Swedish currency was converted to Purchasing
      Power Parities US dollar (PPP$). RESULTS: Median age (interquartile range) was 73
      years (18), and the proportion of women was 48%. The majority of the direct costs
      (78%) was associated with hospitalization, whereas 20% was associated with
      municipality services during 1 year after a first-ever stroke. Only 1% of all
      direct costs were related to primary health care and 1% to medication. The level
      of costs for patients with stroke was correlated with the presence of spasticity
      as measured with the modified Ashworth scale (r(s)=0.524) and with the degree of
      disability as measured with modified Rankin Scale (r(s)=0.624). The mean (median,
      interquartile range) direct cost for stroke patients with spasticity was PPP$
      84,195 (72,116, 53,707) compared with PPP$ 21,842 (12,385, 17,484) for patients
      with stroke without spasticity (P<0.001). CONCLUSIONS: Direct costs for 12-month
      stroke survivors are 4 times higher than direct costs for patients with stroke
      without spasticity during the first year after the event.

PMID- 20044536
TI  - Options to restrict hematoma expansion after spontaneous intracerebral
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Secondary expansion of hematoma after spontaneous
      intracerebral hemorrhage occurs frequently and early with the potential sequelae
      of functional deterioration or death. The aim of this topical review is to give a
      summary of current evidence- and experience-based options to avoid or attenuate
      hematoma expansion. METHOD: We reviewed the literature of the past 10 years on
      efforts to restrict spontaneous intracerebral hemorrhage expansion by searching
      Medline and adding related articles known to us. Based on evidence, current
      guidelines, and our own clinical practice, we have collected consistent and
      inconsistent pieces of data. These were differentiated according to surgical
      versus medical approaches, weighed and discussed with regard to expectable
      benefit, potential risk, and practicability. Finally, we have outlined promising
      future approaches. RESULTS: Although consistent evidence on the topic is
      generally limited, some important studies have provided data on risk factors
      predicting spontaneous intracerebral hemorrhage expansion implying ways of
      directing therapy toward these risk factors. Large trials have shed light on 4
      major efforts to avoid hematoma expansion: surgical hematoma treatment, reduction
      of hypertension, reversal of coagulopathies or anticoagulants, and hemostatic
      therapy. The results were largely disappointing but provide insights for new
      trials. Future strategies include the combination of surgical and medical
      treatment and the use of neuroprotectants. CONCLUSIONS: Early restriction of
      intracerebral hemorrhage is of paramount importance because secondary volume
      expansion leads to outcome deterioration and death. Although there appear to be
      few indications for neurosurgical measures, nonsurgical measures such as
      reduction of hypertension and normalization of altered coagulation seem to be
      beneficial. However, the routine use of coagulation factors outside of warfarin
      associated spontaneous intracerebral hemorrhage cannot generally be recommended
      at present. The same applies for future approaches such as combined medical
      surgical approaches and neuroprotective therapies at this point.

PMID- 20044537
TI  - Vision is precious: a successful behavioral intervention to increase the rate of
      screening for diabetic retinopathy for inner-city adults.
AB  - PURPOSE: This purpose of this report is to describe a successful telephone
      intervention to increase the rate of diabetic retinopathy screening, its
      implementation with English and Spanish speakers, and the characteristics of
      those who benefited most from the intervention. METHODS: Participants in the
      telephone group (N = 305) received a tailored intervention from trained health
      educators who were ethnically diverse and representative of the community. The
      main outcome for the randomized controlled study was documented receipt of a
      dilated fundus examination (DFE) within the 6-month study window. Exploratory
      analyses focused on examining the factors that contribute to receiving a DFE
      within 6 months for participants in the tailored telephone intervention using
      Pearson chi(2) and logistic regression analysis. RESULTS: Participants in the
      telephone intervention who did not receive a DFE had significantly more
      documented steps in the behavioral process than those who did receive a DFE, and
      ethnic concordance of the health educator was not significantly associated with a
      positive outcome in the DFE group. There was a negative association between the
      time spent building rapport and receipt of DFE. As time spent engaging in
      educational activities by telephone increased, the likelihood of receiving a DFE
      increased. CONCLUSIONS: Although the telephone intervention was highly successful
      compared with the print intervention, these process results demonstrate the
      difficulties and challenges of conducting a tailored telephone intervention to
      improve rates of screening in an underserved, diverse urban community.

PMID- 20044538
TI  - Prdm9 controls activation of mammalian recombination hotspots.
AB  - Mammalian meiotic recombination, which preferentially occurs at specialized sites
      called hotspots, ensures the orderly segregation of meiotic chromosomes and
      creates genetic variation among offspring. A locus on mouse chromosome 17, which
      controls activation of recombination at multiple distant hotspots, has been
      mapped within a 181-kilobase interval, three of whose genes can be eliminated as
      candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone
      H3K4 trimethylase that is expressed in early meiosis and whose deficiency results
      in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human
      populations exhibit two predominant alleles and multiple minor alleles. The
      identification of Prdm9 as a protein regulating mammalian recombination hotspots
      initiates molecular studies of this important biological control system.

PMID- 20044539
TI  - PRDM9 is a major determinant of meiotic recombination hotspots in humans and
      mice.
AB  - Meiotic recombination events cluster into narrow segments of the genome, defined
      as hotspots. Here, we demonstrate that a major player for hotspot specification
      is the Prdm9 gene. First, two mouse strains that differ in hotspot usage are
      polymorphic for the zinc finger DNA binding array of PRDM9. Second, the human
      consensus PRDM9 allele is predicted to recognize the 13-mer motif enriched at
      human hotspots; this DNA binding specificity is verified by in vitro studies.
      Third, allelic variants of PRDM9 zinc fingers are significantly associated with
      variability in genome-wide hotspot usage among humans. Our results provide a
      molecular basis for the distribution of meiotic recombination in mammals, in
      which the binding of PRDM9 to specific DNA sequences targets the initiation of
      recombination at specific locations in the genome.

PMID- 20044540
TI  - Detection of gamma-ray emission from the Vela pulsar wind nebula with AGILE.
AB  - Pulsars are known to power winds of relativistic particles that can produce
      bright nebulae by interacting with the surrounding medium. These pulsar wind
      nebulae are observed by their radio, optical, and x-ray emissions, and in some
      cases also at TeV (teraelectron volt) energies, but the lack of information in
      the gamma-ray band precludes drawing a comprehensive multiwavelength picture of
      their phenomenology and emission mechanisms. Using data from the AGILE satellite,
      we detected the Vela pulsar wind nebula in the energy range from 100 MeV to 3
      GeV. This result constrains the particle population responsible for the GeV
      emission and establishes a class of gamma-ray emitters that could account for a
      fraction of the unidentified galactic gamma-ray sources.

PMID- 20044541
TI  - Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic
      recombination.
AB  - Although present in both humans and chimpanzees, recombination hotspots, at which
      meiotic crossover events cluster, differ markedly in their genomic location
      between the species. We report that a 13-base pair sequence motif previously
      associated with the activity of 40% of human hotspots does not function in
      chimpanzees and is being removed by self-destructive drive in the human lineage.
      Multiple lines of evidence suggest that the rapidly evolving zinc-finger protein
      PRDM9 binds to this motif and that sequence changes in the protein may be
      responsible for hotspot differences between species. The involvement of PRDM9,
      which causes histone H3 lysine 4 trimethylation, implies that there is a common
      mechanism for recombination hotspots in eukaryotes but raises questions about
      what forces have driven such rapid change.

PMID- 20044542
TI  - Darwinian evolution of prions in cell culture.
AB  - Prions are infectious proteins consisting mainly of PrP(Sc), a beta sheet-rich
      conformer of the normal host protein PrP(C), and occur in different strains.
      Strain identity is thought to be encoded by PrP(Sc) conformation. We found that
      biologically cloned prion populations gradually became heterogeneous by
      accumulating "mutants," and selective pressures resulted in the emergence of
      different mutants as major constituents of the evolving population. Thus, when
      transferred from brain to cultured cells, "cell-adapted" prions outcompeted their
      "brain-adapted" counterparts, and the opposite occurred when prions were returned
      from cells to brain. Similarly, the inhibitor swainsonine selected for a
      resistant substrain, whereas, in its absence, the susceptible substrain outgrew
      its resistant counterpart. Prions, albeit devoid of a nucleic acid genome, are
      thus subject to mutation and selective amplification.

PMID- 20044543
TI  - 238U/235U variations in meteorites: extant 247Cm and implications for Pb-Pb
      dating.
AB  - The 238U/235U isotope ratio has long been considered invariant in meteoritic
      materials (equal to 137.88). This assumption is a cornerstone of the high
      precision lead-lead dates that define the absolute age of the solar system.
      Calcium-aluminum-rich inclusions (CAIs) of the Allende meteorite display variable
      238U/235U ratios, ranging between 137.409 +/- 0.039 and 137.885 +/- 0.009. This
      range implies substantial uncertainties in the ages that were previously
      determined by lead-lead dating of CAIs, which may be overestimated by several
      million years. The correlation of uranium isotope ratios with proxies for
      curium/uranium (that is, thorium/uranium and neodymium/uranium) provides strong
      evidence that the observed variations of 238U/235U in CAIs were produced by the
      decay of extant curium-247 to uranium-235 in the early solar system, with an
      initial 247Cm/235U ratio of approximately 1.1 x 10(-4) to 2.4 x 10(-4).

PMID- 20044544
TI  - Promoting scientific standards.

PMID- 20044545
TI  - U.S. space policy. Obama backs new launcher and bigger NASA budget.

PMID- 20044546
TI  - Climate change. Senate looms as bigger hurdle after Copenhagen.

PMID- 20044547
TI  - Research management. Protests by staff, advisers rattle Australian Synchrotron.

PMID- 20044550
TI  - Research funding. U.K. physicists cry foul at major budget cuts.

PMID- 20044549
TI  - Scientific publishing. Errors in chemistry claims cast doubt on reactome paper.

PMID- 20044552
TI  - Higher education. Recession hits some sciences hard at Florida State University.

PMID- 20044553
TI  - Ireland. Embryo ruling keeps stem cell research legal.

PMID- 20044554
TI  - In the afterglow of the big bang.

PMID- 20044555
TI  - Gray wolves not out of the woods yet.

PMID- 20044556
TI  - Bushmeat hunting and climate: an indirect link.

PMID- 20044557
TI  - Patents: a threat to innovation?

PMID- 20044558
TI  - Let top students go forth and prosper.

PMID- 20044560
TI  - Research agenda. Opportunities for research and NIH.

PMID- 20044561
TI  - Chemistry. Molecular donuts and donut holes.

PMID- 20044562
TI  - Astronomy. Serendipitous astronomy.

PMID- 20044563
TI  - Chemistry. Janus catalysts direct nanoparticle reactivity.

PMID- 20044564
TI  - Biochemistry. Some enzymes just need a space of their own.

PMID- 20044565
TI  - Neuroscience. Brain activity to rely on?

PMID- 20044566
TI  - Retrospective. Rossiter H. Crozier (1943-2009).

PMID- 20044567
TI  - Lipid rafts as a membrane-organizing principle.
AB  - Cell membranes display a tremendous complexity of lipids and proteins designed to
      perform the functions cells require. To coordinate these functions, the membrane
      is able to laterally segregate its constituents. This capability is based on
      dynamic liquid-liquid immiscibility and underlies the raft concept of membrane
      subcompartmentalization. Lipid rafts are fluctuating nanoscale assemblies of
      sphingolipid, cholesterol, and proteins that can be stabilized to coalesce,
      forming platforms that function in membrane signaling and trafficking. Here we
      review the evidence for how this principle combines the potential for
      sphingolipid-cholesterol self-assembly with protein specificity to selectively
      focus membrane bioactivity.

PMID- 20044568
TI  - Masquerade: camouflage without crypsis.
AB  - Masquerade describes the resemblance of an organism to an inedible object and is
      hypothesized to facilitate misidentification of that organism by its predators or
      its prey. To date, there has been no empirical demonstration of the benefits of
      masquerade. Here, we show that two species of caterpillar obtain protection from
      an avian predator by being misidentified as twigs. By manipulating predators'
      previous experience of the putative model but keeping their exposure to the
      masquerader the same, we determined that predators misidentify masquerading prey
      as their models, rather than simply failing to detect them.

PMID- 20044569
TI  - Polarization-induced hole doping in wide-band-gap uniaxial semiconductor
      heterostructures.
AB  - Impurity-based p-type doping in wide-band-gap semiconductors is inefficient at
      room temperature for applications such as lasers because the positive-charge
      carriers (holes) have a large thermal activation energy. We demonstrate high
      efficiency p-type doping by ionizing acceptor dopants using the built-in
      electronic polarization in bulk uniaxial semiconductor crystals. Because the
      mobile hole gases are field-ionized, they are robust to thermal freezeout effects
      and lead to major improvements in p-type electrical conductivity. The new doping
      technique results in improved optical emission efficiency in prototype
      ultraviolet light-emitting-diode structures. Polarization-induced doping provides
      an attractive solution to both p- and n-type doping problems in wide-band-gap
      semiconductors and offers an unconventional path for the development of solid
      state deep-ultraviolet optoelectronic devices and wide-band-gap bipolar
      electronic devices of the future.

PMID- 20044570
TI  - Translocation of single-stranded DNA through single-walled carbon nanotubes.
AB  - We report the fabrication of devices in which one single-walled carbon nanotube
      spans a barrier between two fluid reservoirs, enabling direct electrical
      measurement of ion transport through the tube. A fraction of the tubes pass
      anomalously high ionic currents. Electrophoretic transport of small single
      stranded DNA oligomers through these tubes is marked by large transient increases
      in ion current and was confirmed by polymerase chain reaction analysis. Each
      current pulse contains about 10(7) charges, an enormous amplification of the
      translocated charge. Carbon nanotubes simplify the construction of nanopores,
      permit new types of electrical measurements, and may open avenues for control of
      DNA translocation.

PMID- 20044571
TI  - Solid nanoparticles that catalyze biofuel upgrade reactions at the water/oil
      interface.
AB  - A recoverable catalyst that simultaneously stabilizes emulsions would be highly
      advantageous in streamlining processes such as biomass refining, in which the
      immiscibility and thermal instability of crude products greatly complicates
      purification procedures. Here, we report a family of solid catalysts that can
      stabilize water-oil emulsions and catalyze reactions at the liquid/liquid
      interface. By depositing palladium onto carbon nanotube-inorganic oxide hybrid
      nanoparticles, we demonstrate biphasic hydrodeoxygenation and condensation
      catalysis in three substrate classes of interest in biomass refining. Microscopic
      characterization of the emulsions supports localization of the hybrid particles
      at the interface.

PMID- 20044572
TI  - Unveiling the transient template in the self-assembly of a molecular oxide
      nanowheel.
AB  - Self-assembly has proven a powerful means of preparing structurally intricate
      nanomaterials, but the mechanism is often masked by the common one-pot mixing
      procedure. We employed a flow system to study the steps underlying assembly of a
      previously characterized molybdenum oxide wheel 3.6 nanometers in diameter. We
      observed crystallization of an intermediate structure in which a central {Mo36}
      cluster appears to template the assembly of the surrounding {Mo150} wheel. The
      transient nature of the template is demonstrated by its ejection after the wheel
      is reduced to its final electronic state. The template's role in the self
      assembly mechanism is further confirmed by the deliberate addition of the
      template to the reaction mixture, which greatly accelerates the assembly time of
      the {Mo150} wheel and increases the yield.

PMID- 20044573
TI  - Synchronous deglacial overturning and water mass source changes.
AB  - Understanding changes in ocean circulation during the last deglaciation is
      crucial to unraveling the dynamics of glacial-interglacial and millennial climate
      shifts. We used neodymium isotope measurements on postdepositional iron-manganese
      oxide coatings precipitated on planktonic foraminifera to reconstruct changes in
      the bottom water source of the deep western North Atlantic at the Bermuda Rise.
      Comparison of our deep water source record with overturning strength proxies
      shows that both the deep water mass source and the overturning rate shifted
      rapidly and synchronously during the last deglacial transition. In contrast, any
      freshwater perturbation caused by Heinrich event 1 could have only affected
      shallow overturning. These findings show how changes in upper-ocean overturning
      associated with millennial-scale events differ from those associated with whole
      ocean deglacial climate events.

PMID- 20044574
TI  - Structure and mechanisms of a protein-based organelle in Escherichia coli.
AB  - Many bacterial cells contain proteinaceous microcompartments that act as simple
      organelles by sequestering specific metabolic processes involving volatile or
      toxic metabolites. Here we report the three-dimensional (3D) crystal structures,
      with resolutions between 1.65 and 2.5 angstroms, of the four homologous proteins
      (EutS, EutL, EutK, and EutM) that are thought to be the major shell constituents
      of a functionally complex ethanolamine utilization (Eut) microcompartment. The
      Eut microcompartment is used to sequester the metabolism of ethanolamine in
      bacteria such as Escherichia coli and Salmonella enterica. The four Eut shell
      proteins share an overall similar 3D fold, but they have distinguishing
      structural features that help explain the specific roles they play in the
      microcompartment. For example, EutL undergoes a conformational change that is
      probably involved in gating molecular transport through shell protein pores,
      whereas structural evidence suggests that EutK might bind a nucleic acid
      component. Together these structures give mechanistic insight into bacterial
      microcompartments.

PMID- 20044575
TI  - The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally
      transmissible cancer.
AB  - The Tasmanian devil, a marsupial carnivore, is endangered because of the
      emergence of a transmissible cancer known as devil facial tumor disease (DFTD).
      This fatal cancer is clonally derived and is an allograft transmitted between
      devils by biting. We performed a large-scale genetic analysis of DFTD with
      microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing
      of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a
      monophyletic clonally transmissible tumor and suggest that the disease is of
      Schwann cell origin. On the basis of these results, we have generated a
      diagnostic marker for DFTD and identify a suite of genes relevant to DFTD
      pathology and transmission. We provide a genomic data set for the Tasmanian devil
      that is applicable to cancer diagnosis, disease evolution, and conservation
      biology.

PMID- 20044576
TI  - O-mannosyl phosphorylation of alpha-dystroglycan is required for laminin binding.
AB  - Alpha-dystroglycan (alpha-DG) is a cell-surface glycoprotein that acts as a
      receptor for both extracellular matrix proteins containing laminin-G domains and
      certain arenaviruses. Receptor binding is thought to be mediated by a
      posttranslational modification, and defective binding with laminin underlies a
      subclass of congenital muscular dystrophy. Using mass spectrometry- and nuclear
      magnetic resonance (NMR)-based structural analyses, we identified a
      phosphorylated O-mannosyl glycan on the mucin-like domain of recombinant alpha
      DG, which was required for laminin binding. We demonstrated that patients with
      muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, as well as
      mice with myodystrophy, commonly have defects in a postphosphoryl modification of
      this phosphorylated O-linked mannose, and that this modification is mediated by
      the like-acetylglucosaminyltransferase (LARGE) protein. These findings expand our
      understanding of the mechanisms that underlie congenital muscular dystrophy.

PMID- 20044577
TI  - The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana.
AB  - To take complete advantage of information on within-species polymorphism and
      divergence from close relatives, one needs to know the rate and the molecular
      spectrum of spontaneous mutations. To this end, we have searched for de novo
      spontaneous mutations in the complete nuclear genomes of five Arabidopsis
      thaliana mutation accumulation lines that had been maintained by single-seed
      descent for 30 generations. We identified and validated 99 base substitutions and
      17 small and large insertions and deletions. Our results imply a spontaneous
      mutation rate of 7 x 10(-9) base substitutions per site per generation, the
      majority of which are G:C-->A:T transitions. We explain this very biased spectrum
      of base substitution mutations as a result of two main processes: deamination of
      methylated cytosines and ultraviolet light-induced mutagenesis.

PMID- 20044579
TI  - High-throughput screening for Kv1.3 channel blockers using an improved FLIPR
      based membrane-potential assay.
AB  - Voltage-gated K(+) channels are potential drug targets for an increasing number
      of disease indications. Searching for compounds that modulate K(+) channel
      activities by high-throughput screening (HTS) is becoming a standard approach in
      the drug discovery effort. Here the authors report an improved fluorometric
      imaging plate reader (FLIPR) membrane potential assay for Kv1.3 K(+) channel HTS.
      They have found that the Chinese hamster ovary (CHO) cells have endogenous
      membrane electrogenic transporters that contribute to maintaining membrane
      potential. Blocking the recombinant K(+) channels in the overexpressing CHO cell
      line hardly changed the membrane potential. Inhibition of the endogenous
      transporters is essential to achieve the required assay robustness. The authors
      identified the optimal assay conditions and designed a simple assay format. After
      an HTS campaign using this assay, various chemical series of Kv1.3 channel
      blockers have been identified and confirmed by the automated electrophysiological
      IonWorks assay. The correlation in dose response between FLIPR and IonWorks was
      established by biophysical modeling and experimental data. After characterization
      using patch-clamp recording, both use-dependent and use-independent compounds
      were identified. Some compounds possess nanomolar potency, indicating that the
      FLIPR assay is effective for successfully identifying K(+) channel blockers as
      novel drug candidates.

PMID- 20044580
TI  - Khat alters the phenotype of in vitro-reconstructed human oral mucosa.
AB  - Khat-chewing has been associated with oral lesions including oral cancer, but the
      mechanisms leading to their development are not known. We hypothesized that khat
      interferes with the physiological processes of the oral mucosa, such as cell
      proliferation and differentiation, and aimed at investigating the effects of khat
      exposure on in vitro-reconstructed human normal buccal mucosa. Khat decreased
      cell proliferation, epithelial thickness, and cytokeratin 13 expression, while
      inducing premature expression of p21(Waf1/Cip1), transglutaminases, involucrin,
      and filaggrin. This suggests that khat is able to induce abnormal differentiation
      of the buccal epithelium. Khat-induced alterations were accompanied by increased
      levels of p38 and were reversed by p38 inhibition, pointing to p38 as the key
      player in this process. The morphological changes described herein mirror the in
      vivo changes previously described in khat users, and demonstrate for the first
      time that khat induces pathological alterations in human buccal mucosa, providing
      evidence that raises concerns about the effects of khat use on oral health.

PMID- 20044581
TI  - Identification of a suppressor element in the amelogenin promoter.
AB  - Amelogenin expression is regulated in a cell-type- specific manner. Investigators
      have previously identified an enhancer element by using the 5' flanking sequence
      of the amelogenin promoter. However, the cell-type-specific regulation of the
      amelogenin gene remains poorly understood. In some genes, the first intron
      regulates tissue-specific expression. We hypothesized that intron 1 is important
      for the cell-type-specific regulation of amelogenin expression. We identified a
      suppressor element between -74 and -464. We also found enhancer activity in
      intron 1. Additionally, we found that the suppressor element in the promoter
      region suppressed intron 1 enhancer activity. The suppressor and the enhancers
      acted in an ameloblast-like cell line, but not in HeLa cells. Mutation of the Oct
      1 binding sites reversed the suppressor activity, suggesting that Oct-1 sites are
      essential for suppression. These results suggest that Oct-1 and intron 1 may
      contribute to cell-type-specific amelogenin expression.

PMID- 20044582
TI  - Markov decision processes: a tool for sequential decision making under
      uncertainty.
AB  - We provide a tutorial on the construction and evaluation of Markov decision
      processes (MDPs), which are powerful analytical tools used for sequential
      decision making under uncertainty that have been widely used in many industrial
      and manufacturing applications but are underutilized in medical decision making
      (MDM). We demonstrate the use of an MDP to solve a sequential clinical treatment
      problem under uncertainty. Markov decision processes generalize standard Markov
      models in that a decision process is embedded in the model and multiple decisions
      are made over time. Furthermore, they have significant advantages over standard
      decision analysis. We compare MDPs to standard Markov-based simulation models by
      solving the problem of the optimal timing of living-donor liver transplantation
      using both methods. Both models result in the same optimal transplantation policy
      and the same total life expectancies for the same patient and living donor. The
      computation time for solving the MDP model is significantly smaller than that for
      solving the Markov model. We briefly describe the growing literature of MDPs
      applied to medical decisions.

PMID- 20044583
TI  - Sudden death during adjuvant trastuzumab therapy of breast cancer.

PMID- 20044585
TI  - Site comparison of selected aerosol samplers in the wood industry.
AB  - Several samplers (IOM, CIP 10-I v1, ACCU-CAP, and Button) were evaluated at
      various wood industry companies using the CALTOOL system. The results obtained
      show that compared to the CALTOOL mouth, which can be considered to be
      representative of the exposure of a person placed at the same location under the
      same experimental conditions, the concentrations measured by the IOM, CIP 10-I
      v1, and ACCU-CAP samplers are not significantly different (respectively, 1.12,
      0.94, and 0.80 compared to 1.00), the Button sampler (0.86) being close to the
      ACCU-CAP sampler. Comparisons of dust concentrations measured using both a closed
      face cassette (CFC) and one of the above samplers were also made. In all, 235
      sampling pairs (sampler + CFC) taken at six companies provided us with a
      comparison of concentrations measured using IOM, CIP 10-I v1, ACCU-CAP, and
      Button samplers with concentrations measured using a CFC. All the studied
      samplers collected systematically more dust than the CFC (2.0 times more for the
      IOM sampler, 1.84 times more for the CIP 10-I v1 sampler, 1.68 times more for the
      ACCU-CAP sampler, and 1.46 times more for the Button sampler). The literature
      most frequently compares the IOM sampler with the CFC: published results
      generally show larger differences compared with the CFC than those found during
      our research. There are several explanations for this difference, one of which
      involves CFC orientation during sampling. It has been shown that concentrations
      measured using a CFC are dependent on its orientation. Different CFC positions
      from one sampling session to another are therefore likely to cause differences
      during CFC-IOM sampler comparisons.

PMID- 20044584
TI  - Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung
      tissue and lung cancer risk.
AB  - Epidemiological and mechanistic evidence on the association of quercetin-rich
      food intake with lung cancer risk and carcinogenesis are inconclusive. We
      investigated the role of dietary quercetin and the interaction between quercetin
      and P450 and glutathione S-transferase (GST) polymorphisms on lung cancer risk in
      1822 incident lung cancer cases and 1991 frequency-matched controls from the
      Environment And Genetics in Lung cancer Etiology study. In non-tumor lung tissue
      from 38 adenocarcinoma patients, we assessed the correlation between quercetin
      intake and messenger RNA expression of the same P450 and GST metabolic genes.
      Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for sex
      specific quintiles of intake were calculated using unconditional logistic
      regression adjusting for putative risk factors. Frequent intake of quercetin-rich
      foods was inversely associated with lung cancer risk (OR = 0.49; 95% CI: 0.37
      0.67; P-trend < 0.001) and did not differ by P450 or GST genotypes, gender or
      histological subtypes. The association was stronger in subjects who smoked >20
      cigarettes per day (OR = 0.35; 95% CI: 0.19-0.66; P-trend = 0.003). Based on a
      two-sample t-test, we compared gene expression and high versus low consumption of
      quercetin-rich foods and observed an overall upregulation of GSTM1, GSTM2, GSTT2,
      and GSTP1 as well as a downregulation of specific P450 genes (P-values < 0.05,
      adjusted for age and smoking status). In conclusion, we observed an inverse
      association of quercetin-rich food with lung cancer risk and identified a
      possible mechanism of quercetin-related changes in the expression of genes
      involved in the metabolism of tobacco carcinogens in humans. Our findings suggest
      an interplay between quercetin intake, tobacco smoking, and lung cancer risk.
      Further research on this relationship is warranted.

PMID- 20044586
TI  - Workplace determinants of endotoxin exposure in dental healthcare facilities in
      South Africa.
AB  - OBJECTIVES: Aerosols generated during dental procedures have been reported to
      contain endotoxin as a result of bacterial contamination of dental unit water
      lines. This study investigated the determinants of airborne endotoxin exposure in
      dental healthcare settings. METHODS: The study population included dental
      personnel (n = 454) from five academic dental institutions in South Africa.
      Personal air samples (n = 413) in various dental jobs and water samples (n = 403)
      from dental handpieces and basin taps were collected. The chromogenic-1000
      limulus amebocyte lysate assay was used to determine endotoxin levels. Exposure
      metrics were developed on the basis of individually measured exposures and
      average levels within each job category. Analysis of variance and multivariate
      linear regression models were constructed to ascertain the determinants of
      exposure in the dental group. RESULTS: There was a 2-fold variation in personal
      airborne endotoxin from the least exposed (administration) to the most exposed
      (laboratory) jobs (geometric mean levels: 2.38 versus 5.63 EU m(-3)). Three
      percent of personal samples were above DECOS recommended exposure limit (50 EU m(
      3)). In the univariate linear models, the age of the dental units explained the
      most variability observed in the personal air samples (R(2) = 0.20, P < 0.001),
      followed by the season of the year (R(2) = 0.11, P < 0.001). Other variables such
      as institution and total number of dental units per institution also explained a
      modest degree of variability. A multivariate model explaining the greatest
      variability (adjusted R(2) = 0.40, P < 0.001) included: the age of institution
      buildings, total number of dental units per institution, ambient temperature,
      ambient air velocity, endotoxin levels in water, job category (staff versus
      students), dental unit model type and age of dental unit. CONCLUSIONS: Apart from
      job type, dental unit characteristics are important predictors of airborne
      endotoxin levels in this setting.

PMID- 20044587
TI  - A novel method to detect proteins evolving at correlated rates: identifying new
      functional relationships between coevolving proteins.
AB  - Interacting proteins evolve at correlated rates, possibly as the result of
      evolutionary pressures shared by functional groups and/or coevolution between
      interacting proteins. This evolutionary signature can be exploited to learn more
      about protein networks and to infer functional relationships between proteins on
      a genome-wide scale. Multiple methods have been introduced that detect correlated
      evolution using amino acid distances. One assumption made by these methods is
      that the neutral rate of nucleotide substitution is uniform over time; however,
      this is unlikely and such rate heterogeneity would adversely affect amino acid
      distance methods. We explored alternative methods that detect correlated rates
      using protein-coding nucleotide sequences in order to better estimate the rate of
      nonsynonymous substitution at each branch (d(N)) normalized by the underlying
      synonymous substitution rate (d(S)). Our novel likelihood method, which was
      robust to realistic simulation parameters, was tested on Drosophila nuclear pore
      proteins, which form a complex with well-documented physical interactions. The
      method revealed significantly correlated evolution between nuclear pore proteins,
      where members of a stable subcomplex showed stronger correlations compared with
      those proteins that interact transiently. Furthermore, our likelihood approach
      was better able to detect correlated evolution among closely related species than
      previous methods. Hence, these sequence-based methods are a complementary
      approach for detecting correlated evolution and could be applied genome-wide to
      provide candidate protein-protein interactions and functional group assignments
      using just coding sequences.

PMID- 20044588
TI  - Coping and resilience factors in pediatric oncology nurses.
AB  - It is well established that pediatric oncology is perceived as a setting that is
      personally and professionally demanding. Many sources acknowledge the development
      of conditions, such as burnout, compassion fatigue and vicarious traumatization,
      as a result of being continuously subjected to highly stressful circumstances in
      a professional capacity. There are a myriad of individual and collaborative
      factors that are known to mediate stress in the oncology setting. One such factor
      is resilience. The purpose of this literature review is to investigate what is
      known about coping and its relationship with resilience in assisting pediatric
      oncology nurses to manage work-related stressors. From the themes identified
      within the reviewed studies, it is clear that the applicability of resilience in
      pediatric oncology nursing has not been thoroughly investigated. The literature
      suggests that the presence of resilience among pediatric oncology nurses is
      possible. What is not known is whether there is a link between this resilience
      and ability to cope with the stressors of pediatric oncology.

PMID- 20044589
TI  - Cancer survivorship in children and young adults: a concept analysis.
AB  - Survivorship has been described in a variety of ways. Understanding how
      survivorship is applied in the context of childhood cancer survivors is important
      to the practice of pediatric nursing because it will offer nurses new
      possibilities for providing guidance, support, and assistance in enhancing
      outcomes for childhood cancer survivors and their families. Accordingly, the
      purpose of this article is to provide a conceptual framework that will assist
      nurses in their efforts to attain the common goal of successful survivorship in
      childhood cancer survivors. The method of concept analysis developed by Walker
      and Avant is used. The result is a definition of survivorship that is relevant
      and useful for research and clinical practice in pediatric oncology.

PMID- 20044590
TI  - Detection of left ventricular hypertrophy in rats administered a peroxisome
      proliferator-activated receptor alpha/gamma dual agonist using natriuretic
      peptides and imaging.
AB  - Chronic treatment with suprapharmacologic doses of peroxisome proliferator
      activated receptor (PPAR) agonists has a known potential for causing left
      ventricular hypertrophy (LVH). The mechanism by which LVH develops is not well
      understood nor are biomarkers of it well characterized. Natriuretic peptides are
      important regulators of cardiac growth, blood volume, and arterial pressure and
      may be useful biomarkers of LVH and hemodynamic changes that precede it. We
      measured amino-terminal pro-atrial natriuretic peptide (NTproANP), amino-terminal
      pro-brain natriuretic peptide (NTproBNP), and cardiac troponin I (cTnI)
      concentrations in serum and plasma, as well as transcripts in left ventricular
      heart tissue for atrial natriuretic peptide precursor (Nppa), brain natriuretic
      peptide precursor (Nppb), and myosin heavy chain-beta (Myh7) as potential
      biomarkers of LVH induced by a PPARalpha/gamma dual agonist in Sprague-Dawley
      rats. We used magnetic resonance imaging, echocardiography, and hemodynamics to
      identify structural and functional cardiovascular changes related to the
      biomarkers. Heart-to-brain weight ratios (HW:BrW) were correlated with NTproANP,
      NTproBNP, and cTnI concentrations in serum as well as fold change in expression
      of Nppa and Nppb. LVH was characterized by increased left ventricular wall
      thickness and inner diameter, increased cardiac output, decreased arterial blood
      pressure, and increased heart rate. In these studies, each end point contributed
      to the early detection of LVH, the ability to monitor its progression, and
      demonstrated the ability of NTproANP concentration in serum to predict LVH and
      hemodynamic changes.

PMID- 20044591
TI  - Global gene expression analysis reveals differences in cellular responses to
      hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells.
AB  - Reactive oxygen species-induced oxidative stress in the colon is involved in
      inflammatory bowel diseases and suggested to be associated with colorectal cancer
      risk. However, our insight in molecular responses to different oxygen radicals is
      still fragmentary. Therefore, we studied global gene expression by an extensive
      time series (0.08, 0.25, 0.5, 1, 2, 4, 8, 16, or 24 h) analyses in human colon
      cancer (caco-2) cells after exposure to H(2)O(2) or the superoxide anion donor
      menadione. Differences in gene expression were investigated by hybridization on
      two-color microarrays against nonexposed time-matched control cells. Next to gene
      expression, correlations with related phenotypic markers (8-oxodG levels and cell
      cycle arrest) were investigated. Gene expression analysis resulted in 1404
      differentially expressed genes upon H(2)O(2) challenge and 979 genes after
      menadione treatment. Further analysis of gene expression data revealed how these
      oxidant responses can be discriminated. Time-dependent coregulated genes
      immediately showed a pulse-like response to H(2)O(2), while the menadione-induced
      expression is not restored over 24 h. Pathway analyses demonstrated that H(2)O(2)
      immediately influences pathways involved in the immune function, while menadione
      constantly regulated cell cycle-related pathways Altogether, this study offers a
      novel and detailed insight in the similarities and differences of the time
      dependent oxidative stress responses induced by the oxidants H(2)O(2) and
      menadione and show that these can be discriminated regarding their modulation of
      particular colon carcinogenesis-related mechanisms.

PMID- 20044592
TI  - Calcium-related processes involved in the inhibition of depolarization-evoked
      calcium increase by hydroxylated PBDEs in PC12 cells.
AB  - In vitro studies indicated that hydroxylated polybrominated diphenyl ethers (OH
      PBDEs) have an increased toxic potential compared to their parent congeners. An
      example is the OH-PBDE-induced increase of basal intracellular Ca(2+)
      concentration ([Ca(2+)](i)) by release of Ca(2+) from endoplasmic reticulum (ER)
      and mitochondria and/or influx of extracellular Ca(2+). ER and mitochondria
      regulate Ca(2+) homeostasis in close association with voltage-gated Ca(2+)
      channels (VGCCs). Therefore, effects of (OH-)PBDEs on the depolarization-evoked
      (100 mM K(+)) net increase in [Ca(2+)](i) (depolarization-evoked [Ca(2+)](i))
      were measured in neuroendocrine pheochromocytoma cells using the Ca(2+)
      responsive dye Fura-2. OH-PBDEs dose dependently inhibited depolarization-evoked
      [Ca(2+)](i). This inhibition was potentiated by a preceding increase in basal
      [Ca(2+)](i). Especially at higher concentrations of OH-PBDEs (5-20 microM), large
      increases in basal [Ca(2+)](i) strongly inhibited depolarization-evoked
      [Ca(2+)](i). The inhibition appeared more sensitive to increases in basal
      [Ca(2+)](i) by Ca(2+) release from intracellular stores (by 3-OH-BDE-47 or 6'-OH
      BDE-49) compared to those by influx of extracellular Ca(2+) (by 6-OH-BDE-47 or 5
      OH-BDE-47). The expected [Ca(2+)](i) difference close to the membrane suggests
      involvement of Ca(2+)-dependent regulatory processes close to VGCCs. When
      coapplied with depolarization, some OH-PBDEs induced also moderate direct
      inhibition of depolarization-evoked [Ca(2+)](i). Polybrominated diphenyl ethers
      and methoxylated BDE-47 affected neither basal nor depolarization-evoked
      [Ca(2+)](i), except for BDE-47, which moderately increased fluctuations in basal
      [Ca(2+)](i) and depolarization-evoked [Ca(2+)](i). These findings demonstrate
      that OH-PBDEs inhibit depolarization-evoked [Ca(2+)](i) depending on preceding
      basal [Ca(2+)](i). Related environmental pollutants that affect Ca(2+)
      homeostasis (e.g., polychlorinated biphenyls) may thus also inhibit
      depolarization-evoked [Ca(2+)](i), justifying further investigation of possible
      mixture effects of environmental pollutants on Ca(2+) homeostasis.

PMID- 20044594
TI  - Junior doctors need training in sickness certification.
AB  - BACKGROUND: A recent report highlights the need for clear standards of practice
      regarding working-age health. Despite this, little is known about training or
      performance of sickness certification by junior doctors in secondary care. AIMS:
      To see what sickness certification training had been received by practising
      hospital postgraduate trainees and establish how confident and knowledgeable they
      were in this area. We also evaluated the feasibility and face validity of a paper
      based educational module. METHODS: We surveyed 51 junior doctors in a variety of
      specialties, at all grades. Questions concerned training and practice of sickness
      certification and assessing capacity for work. A knowledge test regarding formal
      guidelines, use of forms and self-certification was undertaken, before
      participants evaluated a 10 min training module. RESULTS: Seventy-nine per cent
      of participants lacked knowledge in sickness certification, and 55% were not
      confident to assess capacity for work; 66% had received no training at all and
      71% participants followed no guideline. Many could not identify or explain the
      use of certificates: MED-3 (50 or 71%, respectively), MED-5 (42 or 38%,
      respectively), MED-10 (0 or 17%, respectively), RM-7 (2 or 6%, respectively) and
      DS-1500 (6 or 8%, respectively). Majority of participants thought that an
      educational module could increase knowledge and skill in sickness certification
      (96%) and in assessing work capacity (74%). CONCLUSIONS: Junior doctors are
      involved in sickness certification, but there is a lack of training at
      undergraduate and postgraduate level, and many are unaware of formal guidance.
      The majority of junior doctors are concerned about lack of knowledge in this area
      and to a lesser extent in assessing patients' capacity to work. A simple
      educational module could improve confidence, knowledge and skills in sickness
      certification.

PMID- 20044593
TI  - Differential gene regulation by the human and mouse aryl hydrocarbon receptor.
AB  - The human aryl hydrocarbon receptor (hAHR) and mouse aryl hydrocarbon receptor
      (mAHR(b)) share limited (58%) transactivation domain (TAD) sequence identity.
      Compared to the mAHR(b) allele, the hAHR displays 10-fold lower relative affinity
      for prototypical ligands, such as 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD).
      However, in previous studies, we have demonstrated that the hAHR can display a
      higher relative ligand-binding affinity than the mAHR(b) for specific AHR
      ligands, such as indirubin. Each receptor has also been shown to differentially
      recruit LXXLL coactivator motif proteins and to utilize different TAD subdomains
      in gene transactivation. Using hepatocytes isolated from C57BL/6J mice (Ahr(b/b))
      and AHR(Ttr) transgenic mice, which express hAHR protein specifically in
      hepatocytes, we investigated whether the hAHR and mAHR(b) differentially regulate
      genes. DNA microarray and quantitative PCR analysis of Ahr(b/b) and AHR(Ttr)
      primary mouse hepatocytes treated with 10nM TCDD revealed that a number of
      established AHR target genes such as Cyp1a1 and Cyp1b1 are significantly induced
      by both receptors. Remarkably, of the 1752 genes induced by mAHR(b) and 1186
      genes induced by hAHR, only 265 genes (approximately 18%) were significantly
      activated by both receptors in response to TCDD. Conversely, of the 1100 and 779
      genes significantly repressed in mAHR(b) and hAHR hepatocytes, respectively, only
      462 (approximately 49%) genes were significantly repressed by both receptors in
      response to TCDD treatment. Genes identified as differentially expressed are
      known to be involved in a number of biological pathways, including cell
      proliferation and inflammatory response, which suggest that compared to the
      mAHR(b), the hAHR may play contrasting roles in TCDD-induced toxicity and
      endogenous AHR-mediated gene regulation.

PMID- 20044595
TI  - The structure of the extended psychosis phenotype in early adolescence--a cross
      sample replication.
AB  - The extended psychosis phenotype, or the expression of nonclinical positive
      psychotic experiences, is already prevalent in adolescence and has a dose
      response risk relationship with later psychotic disorder. In 2 large adolescent
      general population samples (n = 5422 and n = 2230), prevalence and structure of
      the extended psychosis phenotype was investigated. Positive psychotic
      experiences, broadly defined, were reported by the majority of adolescents.
      Exploratory analysis with Structural Equation Modelling (Exploratory Factor
      Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested
      that psychotic experiences were best represented by 5 underlying dimensions; CFA
      in sample 2 provided a replication of this model. Dimensions were labeled
      Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs.
      Prevalences differed strongly, Hallucinations having the lowest and Paranoia
      having the highest rates. Girls reported more experiences on all dimensions,
      except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations,
      Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were
      associated with distress and general measures of psychopathology. Thus, only some
      of the dimensions of the extended psychosis phenotype in young people may
      represent a continuum with more severe psychopathology and predict later
      psychiatric disorder.

PMID- 20044596
TI  - HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in
      vivo mouse glioblastoma multiforme model.
AB  - BACKGROUND: Statins are thought to have tumorolytic properties, reducing
      angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural
      pericytes within the tumor vascular tree. MATERIALS AND METHODS: An orthotopic
      mouse glioblastoma (GL-26) model was used to investigate the effect of
      simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into
      the striatum of C5LKa mice treated with either control, low- or high-dose
      simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and
      pericytic cells within the vascular tree. RESULTS: Low-dose simvastatin increased
      necrosis and apoptosis compared to both control and high-dose simvastatin groups.
      High-dose simvastatin increased vessel caliber by reducing pericytic cells along
      the tumor vessel wall compared to both control and low-dose simvastatin groups.
      CONCLUSION: Simvastatin has a dual effect on tumorigenesis. At high doses, it may
      worsen instead of 'normalizing' tumor angio-architecture, albeit low doses affect
      tumor cell survival by promoting necrosis and apoptosis.

PMID- 20044598
TI  - L1-CAM as a target for treatment of cancer with monoclonal antibodies.
AB  - L1 cell adhesion molecule (L1-CAM) is a neuronal adhesion molecule which is
      expressed in many tumor entities. L1-CAM was shown to be involved in
      proliferation, invasion and metastasis both in vitro and in vivo. L1-CAM is
      engaged in homophilic interactions and complexes with many other ligands in a
      context-dependent manner. Activation and modulation of the extracellular signal
      related kinase pathway by L1-CAM has been documented. In normal tissues, L1-CAM
      expression is restricted to nerve bundles and kidney tubules; however, L1-CAM is
      expressed in many tumor entities and, with the exception of neuroblastoma, L1-CAM
      expression correlates with poor prognosis. L1-CAM occurs in two isoforms, full
      length L1-CAM and a variant in which exons 2 and 27 have been deleted.
      Preclinical experiments with available monoclonal antibodies are summarized and
      L1-CAM is analysed as a target for treatment of cancer with monoclonal
      antibodies.

PMID- 20044597
TI  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is pyruvylated during 3
      bromopyruvate mediated cancer cell death.
AB  - BACKGROUND: The pyruvic acid analog 3-bromopyruvate (3BrPA) is an alkylating
      agent known to induce cancer cell death by blocking glycolysis. The anti
      glycolytic effect of 3BrPA is considered to be the inactivation of glycolytic
      enzymes. Yet, there is a lack of experimental documentation on the direct
      interaction of 3BrPA with any of the suggested targets during its anticancer
      effect. METHODS AND RESULTS: In the current study, using radiolabeled ((14)C)
      3BrPA in multiple cancer cell lines, glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) was identified as the primary intracellular target of 3BrPA, based on two
      dimensional (2D) gel electrophoretic autoradiography, mass spectrometry and
      immunoprecipitation. Furthermore, in vitro enzyme kinetic studies established
      that 3BrPA has marked affinity to GAPDH. Finally, Annexin V staining and active
      caspase-3 immunoblotting demonstrated that apoptosis was induced by 3BrPA.
      CONCLUSION: GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the
      primary intracellular target in 3BrPA mediated cancer cell death.

PMID- 20044600
TI  - Mistletoe lectin binds to multidrug resistance-associated protein MRP5.
AB  - BACKGROUND: Mistletoe lectins (MLs) are the active components of aqueous
      mistletoe extracts widely used in complementary cancer therapy, however, it is
      not clear if they bind to carbohydrate residues only or whether they interact
      with proteins as well. Protein-protein interactions do not seem unlikely as MLs
      act at very low molar concentrations usually observed with peptide-peptide
      interactions only and not seen with lectin-sugar interactions. MATERIALS AND
      METHODS: In order to detect protein-protein interactions a random peptide library
      was screened for the ability to bind to MLs. RESULTS: MLs bound to peptides
      showing homologies to multidrug resistance-associated protein 5 (MRP5). However,
      the MLs only slightly modified the MRP5 efflux pump, while periodate treatment to
      inhibit cell membrane binding via glycan completely abolished the ML-I binding
      sites in MRP5 overexpressing cells. CONCLUSION: The protein sequence is not
      important for ML-I binding, indicating that the biological activity of MLs can
      most likely be attributed to the sugar chains.

PMID- 20044599
TI  - Galectin-8 up-regulation during hypopharyngeal and laryngeal tumor progression
      and comparison with galectin-1, -3 and -7.
AB  - AIM: To define specific staining patterns for the adhesion/growth-regulatory
      lectin tandem-repeat-type galectin-8 in hypopharyngeal and laryngeal tumor
      progression and relate these parameters to galectins 1, 3 and 7 in the quest to
      explore the galectin network. MATERIALS AND METHODS: The level of expression of
      galectin-8 was determined immunohistochemically in a series of 18 and 16 cases of
      tumor-free epithelium, 24 and 10 cases of low-grade dysplasia, 22 and 15 cases of
      high-grade dysplasia located in peri-tumoral area of 74 and 37 hypopharyngeal and
      laryngeal carcinomas. RESULTS: Marked upregulation in galectin-8 staining
      intensity and immunopositive area in malignancy versus dysplasia was seen in
      hypopharyngeal cancer (p<10(-6)), in laryngeal cancer for labeling index and high
      grade dysplasia/carcinoma (p<10(-6)). No correlation to recurrence was
      delineated. CONCLUSION: The presented data revealed a divergence within the
      galectin-1, -3, -7 and -8 network during tumor progression.

PMID- 20044601
TI  - Simultaneous identification and quantification of proteins by differential
      (16)O/(18)O labeling and UPLC-MS/MS applied to mouse cerebellar phosphoproteome
      following irradiation.
AB  - Differential proteolytic (18)O labeling is a cost-effective but not commonly used
      method in the field of quantitative proteomics based on mass spectrometry (MS).
      In most cases, peptide identification is performed at the MS/MS level followed by
      peptide quantification at the MS level. In this study, identification and
      quantification of (18)O-labeled peptides was performed in a single step at the
      MS/MS level using the MASCOT 2.2 search engine, and the instrumental conditions
      for acquisition of ultra performance liquid chromatography electrospray MS/MS
      (UPLC-ESI-MS/MS) data were adapted accordingly. Using analysis of standard
      peptide and protein mixtures prepared by differential (16)O/(18)O labeling, under
      these conditions automated MS/MS data acquisition and evaluation delivered
      correct data. Linearity and reproducibility of this approach indicated excellent
      performance. In addition, the method was applied to relative quantification of
      protein phosphorylation in mouse brain following treatment with ionizing
      radiation. The analysis led to automated quantification of 342 proteins and 174
      phosphorylation sites, 24 of which were up- or down-regulated by a factor of 2 or
      more. The majority of these phosphorylation sites were found to be located in
      target sequences of known protein kinases, showing the activation of kinase
      regulated signaling cascades by irradiation.

PMID- 20044603
TI  - Akt interaction with PLC(gamma) regulates the G(2)/M transition triggered by FGF
      receptors from MDA-MB-231 breast cancer cells.
AB  - BACKGROUND/AIM: Estrogen-independent breast cancer cell growth is under the
      control of fibroblast growth factors receptors (FGFRs), but the role of
      phospholipase C gamma (PLC(gamma)) and Akt, the downstream effectors activated by
      FGFRs, in cell proliferation is still unresolved. MATERIALS AND METHODS: FGFRs
      from highly invasive MDA-MB-231 cells were expressed in Xenopus oocyte, a
      powerful model system to assess the G(2)/M checkpoint regulation. Under FGF1
      stimulation, an analysis of the progression in the M-phase of the cell cycle and
      of the Akt signaling cascades were performed using the phosphatidylinositol-3
      kinase inhibitor, LY294002, and a mimetic peptide of the SH3 domain of
      PLC(gamma). RESULTS: Activated Akt binds and phosphorylates PLC(gamma) before Akt
      targets the tumor suppressor Chfr. Disruption of the Akt-PLC(gamma) interaction
      directs Akt binding to Chfr and accelerates the alleviation of the G(2)/M
      checkpoint. CONCLUSION: The PLC(gamma)-Akt interaction, triggered by FGF
      receptors from estrogen-independent breast cancer cells MDA-MB-231, regulates
      progression in the M-phase of the cell cycle.

PMID- 20044602
TI  - Retinoid-induced histone deacetylation inhibits telomerase activity in estrogen
      receptor-negative breast cancer cells.
AB  - BACKGROUND: Multiple mechanisms regulate cancer-associated telomerase activity at
      the level of human telomerase reverse transcriptase (hTERT) transcription which
      may serve as novel targets for anticancer approaches. MATERIALS AND METHODS: The
      effects of prolonged all-trans retinoic acid (ATRA) exposure on hTERT regulation
      in estrogen receptor-negative SK-BR-3 breast cancer cells were examined. RESULTS:
      ATRA had a profound effect on the morphology and proliferation rate of the SK-BR
      3 cells. ATRA also hindered the ability of these cancer cells to grow
      independently, rendering them more like normal somatic cells. The effect of ATRA
      on the decrease of telomerase activity was found to be associated with a rapid
      decrease in histone H3-lysine 9 acetylation (H3-K9-Ac) of the hTERT promoter.
      Extended-exposure to ATRA in these cells also caused the initiation of a putative
      compensatory mechanism, counteracting the induced surge in apoptosis. CONCLUSION:
      A rapid decrease of H3-K9 acetylation at the hTERT promoter could be an important
      mechanism by which ATRA shuts down telomerase activity and mediates its antitumor
      effects in estrogen receptor-negative breast cancer cells.

PMID- 20044604
TI  - A new amino acid derivative of ursodeoxycholate, (N-L-Glutamyl)-UDCA (UDCA-Glu),
      to selectively release UDCA in the colon.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) is chemoprotective in animal models of
      colon cancer but results from clinical trials have been less impressive probably
      because UDCA is rapidly absorbed in the small intestine and little reaches the
      colon. UDCA-glutamate (Glu), a novel bile acid, was synthesized with the
      objective of utilizing peptide bond cleavage by brush border enzymes to enhance
      delivery of UDCA to the colon. MATERIALS AND METHODS: Qualitative and
      quantitative intestinal intraluminal and fecal bile acid composition measured by
      mass spectrometry was determined in Fisher rats after intragastric administration
      of UDCA, or UDCA-Glu for 5 days. The effect of UDCA and UDCA-Glu on bile flow was
      studied after bile duct canulation. RESULTS: In the small intestine, UDCA was
      found in higher amounts when UDCA was administered compared with UDCA-Glu (1.50 +
      or - 0.32 vs. 0.75 + or - 0.12 mg). By contrast, UDCA-Glu administration resulted
      in a greater delivery of UDCA to the colon. The fecal bile acid composition
      resembled that of the intraluminal colonic composition and a higher mass of UDCA
      (unconjugated 3.39 + or - 0.30 mg; conjugated 6.40 + or - 1.03 mg) was found in
      rats treated with UDCA-Glu compared to those treated with UDCA (2.27 + or - 0.11
      and. 0.04 + or - 0.01 mg, respectively), establishing increased delivery of UDCA
      to the colon. Both bile acids similarly increased bile flow but the initial
      effect of UDCA was greater than that of UDCA-Glu. CONCLUSION: Conjugation of UDCA
      to glutamic acid reduces its intestinal absorption and biotransformation
      resulting in increased colonic delivery of UDCA. UDCA-Glu may have potential
      application as a pro-drug for enhancing the action of UDCA in the treatment of
      colonic diseases.

PMID- 20044605
TI  - Diarylheptanoids derived from Alpinia officinarum induce apoptosis, S-phase
      arrest and differentiation in human neuroblastoma cells.
AB  - BACKGROUND: We have previously screened many natural products for their cytotoxic
      effects on neuroblastoma cell lines, and two diarylheptanoids derived from
      Alpinia officinarum, 7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one
      (Compound 1) and (5R)-5-methoxy-7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-3
      heptanone (Compound 2), were shown to have potent cytotoxicity. On this basis, a
      detailed study of the antitumor activities of these two diarylheptanoids in
      neuroblastoma cell lines was performed. MATERIALS AND METHODS: Cytotoxicity was
      assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)
      assay. To measure apoptosis, nuclear shrinkage was monitored by Hoechst 33342
      staining, and activation of caspases 3 and 9 was monitored by Western blotting.
      Cell cycle status was evaluated by flow cytometry with propidium iodide staining.
      Differentiated cells were photographed and counted in a randomized fashion.
      RESULTS: Both diarylheptanoids showed significant cytotoxicity against
      neuroblastoma cell lines (IMR-32, SK-N-SH, NB-39). The compounds induced nuclear
      shrinkage and fragmentation, and activated caspase-3 and caspase-9. Flow
      cytometric analysis revealed induction of S-phase cell cycle arrest concurrently
      with an increased sub-G(1) cell population. Moreover, a low concentration (10(-8)
      M) of Compound 1 induced significant neurite branching in the NB-39 cell line.
      CONCLUSION: Diarylheptanoids derived from A. officinarum have marked activity
      against neuroblastoma cells, acting through multiple mechanisms. Our results
      suggest that the two compounds studied here may be useful for the treatment of
      patients with neuroblastoma.

PMID- 20044606
TI  - Infrequent amplification of JUN in hepatocellular carcinoma.
AB  - AIM: To determine whether JUN (the oncogene encoding c-Jun protein) is amplified
      and overexpressed in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: DNA
      copy number aberrations were investigated using a high-density oligonucleotide
      microarray. DNA copy numbers were determined by fluorescence in situ
      hybridization. Genomic DNA and mRNA were quantified using real-time quantitative
      PCR. RESULTS: A novel amplification was found at the chromosomal region 1p32-31
      in a JHH-2 HCC cell line within which JUN is amplified and overexpressed.
      However, no copy number gain of JUN (>2-fold) was observed in 34 primary HCC
      tumors. Rather, a loss of JUN (<0.5-fold) was seen in 13 (38%) out of the 34
      tumors and expression of JUN was significantly lower in 26 (70%) out of the 37
      HCC tumors compared with their nontumorous counterparts. CONCLUSION: Although JUN
      was amplified and overexpressed in JHH-2 HCC cells, amplification and
      overexpression of JUN may be rare in primary HCCs.

PMID- 20044607
TI  - Image analysis of breast cancer immunohistochemistry-stained sections using
      ImageJ: an RGB-based model.
AB  - BACKGROUND: Image analysis of tissue sections using RGB image profiling is a
      modern accepted technique. MATERIALS AND METHODS: A new method of RGB analysis,
      using the freeware ImageJ, is presented which can be applied to sections with
      either nuclear or cytoplasmic staining. The step-by-step process is presented and
      the method is tested using breast cancer specimens immunostained for CK-19 and
      estrogen receptors. RESULTS: This image analysis easily discriminates CK-19 and
      estrogen receptor positivity in prepared breast cancer specimens. The method is
      easy to perform, without the need for previous image transformations. CONCLUSION:
      Compared to previous methods, this method proved more accurate in estimating the
      actual colours that an observer recognizes as positive after immunostaining.
      Further studies are needed to evaluate whether this method is efficient enough to
      be applied in clinical practice.

PMID- 20044608
TI  - The expression of the insulin-like growth factor II, JIP-1 and WT1 genes in
      porcine nephroblastoma.
AB  - c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP-1) is an important
      scaffolding protein in the JNK signalling pathway. It is also believed to play a
      role in the mediation of mitogenic messages from the plasma membrane to the cell
      interior. Previous studies have suggested that the JIP gene is co-regulated with
      the insulin-like growth factor II (IGF-II) gene, thereby contributing to the
      growth stimulatory effects of this potent growth factor. The striking co
      expression of these two genes has been found in murine foetuses as well as in
      primary human embryonic tumours. When six primary Wilms tumours (nephroblastomas)
      from pig were examined, the two genes showed a high degree of co-variation in the
      sense that high or low expression of IGF-II and high or low expression of JIP-1
      ocurred together. By contrast the expression of a third Wilms tumour-related
      gene, WT1, was completely uncorrelated to the expression of IGF-II and JIP. In
      this respect, porcine nephroblastomas resemble human Wilms tumours. This further
      suggests that JIP-1 may play a role in the regulation of IGF-II-driven tumour
      cell proliferation.

PMID- 20044609
TI  - Preoperative plasma level of IL-10 but not of proinflammatory cytokines is an
      independent prognostic factor in patients with gastric cancer.
AB  - There have been many discrepant observations on the serum levels of cytokines in
      cancer patients and their prognostic value. The purpose of this study was to
      determine the plasma levels of pro- and anti-inflammatory cytokines and their
      clinical significance in a large group of patients with gastric carcinoma. The
      levels of tumour necrosis factor alpha (TNF alpha), interleukin-12p40 (IL-12p40),
      IL-12p70, IL-18, IL-10 and soluble TNF receptors I and II sTNF-Rs were
      investigated in the plasma of 136 consecutive patients with biopsy proven gastric
      cancer using specific enzyme-linked immunoabsorbent assays (ELISA). Survival
      curves were estimated using the method of Kaplan and Meier and the differences in
      the survival rates were tested by the log-rank test. For multivariate analysis of
      prognostic factors, the Cox proportional hazard model was used. Proinflammatory
      cytokines and sTNF-Rs were higher in the whole group of patients in comparison to
      healthy volunteers. IL-10 was elevated mostly in advanced disease. The increased
      levels of IL-10 (>10 pg/ml) were associated with significantly poorer survival of
      patients, while the levels of the other cytokines and sTNF-Rs showed no
      correlation with prognosis. The increased level of IL-10 is an independent
      unfavorable prognostic factor in patients with gastric cancer.

PMID- 20044610
TI  - Elevated levels of HMGB1 in cancerous and inflammatory effusions.
AB  - BACKGROUND: Recently, it has become obvious that the HMGB1 protein can act as a
      proinflammatory and proangiogenic mediator when actively secreted by macrophages
      or passively released from necrotic cells playing an important role in the
      pathogenesis of several diseases including cancer. MATERIALS AND METHODS: The
      absolute and relative amount of HMGB1 was measured with an ELISA in different
      effusion types. RESULTS: The amount of HMGB1 protein in the samples differed
      between 0.0004% and 0.0025% of the total sample protein. The mean values of
      transudates were significantly (p<0.001) lower than the mean values of exudates.
      CONCLUSION: HMGB1, a so-called danger signalling protein, was found to be highly
      expressed in human pleural and peritoneal effusions due to cancer and
      inflammation. Compared to transudates the average level of HMGB1 was
      significantly higher in exudates. These results underline the characteristics of
      HMGB1 as a possible target for treatment in advanced cancer as well.

PMID- 20044611
TI  - Estimation of relationship between structure of newly synthesized
      dihydroimidazoles determined by a semiempirical molecular-orbital method and
      their cytotoxicity.
AB  - A semiempirical molecular-orbital method (CAChe 4.9, PM5) was applied to
      delineate the relationship between the cytotoxicity (evaluated by 50% cytotoxic
      concentration, CC(50)) of twelve dihydroimidazole derivatives, their molecular
      weight and the eleven chemical parameters (descriptors) determined by CONFLEX/PM5
      method. There was no correlation between the CC(50) value and heat of formation,
      dipole moment, E(HOMO), E(LUMO), absolute hardness (eta), absolute electron
      negativity (chi), reaction index (omega), length of substituted group in all cell
      lines tested. However, there was good correlation between the CC(50) and the log
      P, or molecular size in all cell lines used. Surface and volume calculated by
      this method are useful in evaluating the cytotoxicity of dihydroimidazole
      derivatives.

PMID- 20044612
TI  - Tumor-specific cytotoxicity and type of cell death induced by gefitinib in oral
      squamous cell carcinoma cell lines.
AB  - Gefitinib is an orally active, selective epidermal growth factor receptor
      tyrosine kinase inhibitor. The present study was aimed at evaluating the
      antitumor activity of gefitinib alone or in combination with other antitumor
      agents. Gefitinib showed higher cytotoxicity against five human tumor cell lines
      (HSC-2, HSC-3, HSC-4, T98G and U87MG) than against three human normal oral cells
      (gingival fibroblast HGF, pulp cell HPC and periodontal ligament fibroblast
      HPLF). Gefitinib showed little or no growth stimulation effects at lower
      concentrations (so-called hormetic effect). Non-cytotoxic concentration of
      gefitinib effectively enhanced the cytotoxicity of docetaxel against HSC-2 and
      T98G cell, but failed to enhance the cytotoxicity of other antitumor agents
      (mitoxantrone, doxorubicin, methotrexate, cisplatin, sodium ascorbate, sodium
      fluoride) or herbal extracts (Drynaria baronii, Angelica sinensis and Cornus
      officinalis Sieb. et Zucc). Gefitinib alone and combined with docetaxel induced
      internucleosomal DNA fragmentation and caspase-3 activation in human
      promyelocytic leukemia HL-60 cells, but not in HSC-2 or T98G cells. Combination
      treatment with gefitinib and docetaxel induced the formation of acidic organelles
      (stained with acridine orange) and mitochondrial shrinkage, vacuolization and
      production of autophagosome and the loss of cell surface microvilli, without
      destruction of cell surface and nuclear membranes in HSC-2 and T98G cells
      (demonstrated by transmission electron microscopy), suggesting the induction of
      autophagy in HSC-2 and T98G cells.

PMID- 20044613
TI  - CDX2 expression in cutaneous metastatic carcinomas and extramammary Paget's
      Disease.
AB  - BACKGROUND: CDX2 is a gene involved in the regulation of intestinal cell
      proliferation/differentiation. It is considered specific for enterocytes and has
      been used for the diagnosis of primary and metastatic colon adenocarcinoma. The
      aim of this study was to assess the usefulness of CDX2 in the diagnosis of
      cutaneous metastatic tumors and extramammary Paget's disease. MATERIALS AND
      METHODS: The immunohistochemical expression of CDX2 was studied in 68 cutaneous
      metastatic tumors of various origins and 14 specimens of extramammary Paget's
      disease. RESULTS: CDX2 expression was found in 3/6 metastases of colon
      adenocarcinoma, 1/1 metastasis of urothelial carcinoma and 1/2 extramammary
      Paget's disease. CONCLUSION: CDX2 appears to be specific for cutaneous metastases
      from intestinal and urothelial carcinomas and is a useful diagnostic marker of
      these tumors. However, its sensitivity is modest, and we advocate its use in
      conjunction with additional immunohistochemical markers. CDX2 seems useful for
      the diagnosis of extramammary Paget's disease associated with an underlying
      colorectal tumor.

PMID- 20044614
TI  - Curcumin induces cell cycle arrest and apoptosis in human osteosarcoma (HOS)
      cells.
AB  - BACKGROUND: Curcumin is a major component of Curcuma longa rhizome and has been
      used as a traditional medicine for centuries. In this study, we showed that
      curcumin induced cell cycle arrest followed by antiproliferation and apoptosis in
      human osteosarcoma (HOS) cells. MATERIALS AND METHODS: Antiproliferative activity
      was measured with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay. Nuclear fragmentation was observed with a fluorescence
      microscope. Flow cytometry was performed to observe cell cycle distribution and
      apoptotic body appearance. Changes in cell cycle regulatory and apoptosis-related
      proteins were investigated by Western blot analysis. RESULTS: The IC(50) value of
      curcumin was approximately 4.0 microg/ml. Induction of apoptosis was evidenced by
      apoptotic body appearance and chromosomal DNA degradation. Flow-cytometric
      analysis indicated that curcumin induced successive G(1)/S and G(2)/M phase
      arrest followed by apoptosis in HOS cells. The G(1)/S and G(2)/S phase arrest was
      accompanied by down-regulation of cyclin D1, cdc2 and cyclin B1, respectively.
      Apoptosis was induced by capspase-3 activation and poly(ADP-ribosyl)polymerase
      (PARP) cleavage. CONCLUSION: Our results demonstrated that curcumin caused death
      of HOS cells by blocking cells successively in G(1)/S and G(2)/M phases and
      activating the caspase-3 pathway.

PMID- 20044615
TI  - Zeranol enhances the proliferation of pre-adipocytes in beef heifers.
AB  - BACKGROUND: The high morbidity and mortality of breast cancer among women is a
      serious problem. The adverse effects of the consumption of beef with zeranol (Z,
      a growth promoter widely used in beef industry in North American) residue on
      human health are still unknown. MATERIALS AND METHODS: The effects of Z
      implantation on the growth of heifer pre-adipocytes were evaluated. The
      stimulatory effects of Z and estradiol-17beta (E(2)) on the proliferation of pre
      adipocytes isolated from control heifers and Z-implanted heifers were measured.
      Real-time PCR and Western-blotting analysis were performed to evaluate the
      expression of cyclin D1 and p53 at both mRNA and protein levels. RESULTS: The
      growth of pre-adipocytes from heifers bearing for 2 months of Z-implants was
      about 12-fold faster than that observed in control heifers. The pre-adipocytes
      isolated from Z-implanted heifers were more sensitive to treatment with Z and
      E(2). Z up-regulated the expression of cyclin D1 and down-regulated p53 in pre
      adipocytes isolated from Z-implanted heifers. CONCLUSION: The implantation of Z
      increases body weight gain by enhancing growth of pre-adipocytes. The stimulation
      of pre-adipocytes division by Z and E(2) might be partially mediated by up
      regulation of cyclin D1 and down-regulation of p53 at mRNA and protein levels.

PMID- 20044616
TI  - Methylation of the MGMT gene is frequently detected in advanced gastric
      carcinoma.
AB  - BACKGROUND: Recently, Herfarth et al. reported that a subset of colorectal tumors
      was characterized by a specific methylation pattern in the MGMT promoter
      associated with reduced MGMT expression. MATERIALS AND METHODS: Methylation
      status of the MGMT gene was examined in primary carcinomas and the corresponding
      normal tissues derived from 38 patients with gastric cancer using quantitative
      methylation-specific PCR (qMSP) and the correlation between the methylation
      status and the clinicopathological findings was evaluated. RESULTS: Aberrant
      methylation of the MGMT gene was detected in 4 out of the 38 (11%) primary
      gastric carcinomas, suggesting that the methylation of MGMT is observed in
      gastric carcinomas as well as colorectal ones. The clinicopathological data were
      correlated with the methylation results. A significant difference was observed in
      the extent of tumor (p=0.0470), lymph node metastasis (p=0.0470), and TNM stage
      (p=0.0377) (Table I). Moreover, a trend was shown toward large maximal tumor size
      in methylated tumors (p=0.134). CONCLUSION: MGMT was more frequently methylated
      in advanced gastric carcinomas.

PMID- 20044617
TI  - PPAR(gamma)/PGC-1(alpha) pathway in E-cadherin expression and motility of HepG2
      cells.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma)
      activation has been proposed as a potential therapeutic strategy for various
      types of human cancer. The aim of this study was to activate PPARgamma and
      overexpress PGC-1alpha in HepG2 cells in order to analyze their effects on cell
      motility and E-cadherin expression. MATERIALS AND METHODS: Adenovirus-mediated
      gene transfer was performed to overexpress PGC-1alpha in HepG2 human hepatoma
      cells. Small interference RNA (siRNA) was used to silence the expression of E
      cadherin and PPARgamma. Cell motility was assessed by transwell cell migration
      analysis. Measurements of mRNA and protein expression were done by quantitative
      RT-PCR and Western blotting. RESULTS: Treatment with synthetic PPARgamma
      agonists, thiazolidinediones (rosiglitazone; troglitazone), and adenovirus
      delivered overexpression of PPARgamma transcriptional coactivator-1alpha (PGC
      1alpha) up-regulated E-cadherin expression and reduced motility of HepG2 cells.
      Using PPARgamma antagonist GW9662, we demonstrated that both PPARgamma-dependent
      and -independent pathways were involved in PGC-1alpha-induced up-regulation of E
      cadherin. In addition, siRNA-mediated knockdown of E-cadherin expression restored
      the motility of PGC-1alpha-overexpressing HepG2 cells, indicating that up
      regulated E-cadherin is responsible for the lower migratory ability of these
      cells. Intriguingly, siRNA-mediated silencing of PPARgamma abolished E-cadherin
      protein expression but also reduced the motility of HepG2 cells. CONCLUSION:
      PPARgamma/PGC-1alpha pathway plays a crucial role in modulating E-cadherin
      expression and motility of HepG2 cells and may be a potential target for the
      prevention of HCC metastasis.

PMID- 20044618
TI  - Antitumor and antiangiogenic activity of cediranib in a preclinical model of
      renal cell carcinoma.
AB  - Cediranib is a highly potent and selective vascular endothelial growth factor
      (VEGF) signaling inhibitor with activity against all three VEGF receptors
      (VEGFRs) that inhibits angiogenesis and growth of human tumor xenografts in vivo.
      The present study evaluated the antitumor and antiangiogenic activity of
      cediranib in the clinically relevant, murine renal cell carcinoma (RENCA) model
      and its biological response using VEGF and sVEGFR-2 as biomarkers. Mice were
      treated with cediranib (5 mg/kg/d p.o.) or vehicle for 2, 8 or 12 days and tumor
      volumes, microvessel density (MVD) and VEGF and sVEGFR-2 plasma concentrations
      were determined. Cediranib treatment (8 and 12 days) led to a significant
      reduction in tumor size (42-50%) and a highly significant reduction in MVD (30
      55%) versus controls. After 12 days' treatment, VEGF plasma concentration
      increased significantly in both cediranib-treated and control animals and this
      increase correlated with tumor size; the cediranib group showed a more pronounced
      increase in VEGF but a reduced tumor volume compared with control animals. Plasma
      concentrations of VEGF reached a plateau in the cediranib group after 17-21 days'
      treatment. sVEGFR-2 concentrations significantly decreased over 12 days in
      controls, whereas they remained stable in cediranib-treated mice. sVEGFR-2 did
      not correlate with tumor volume in controls; mice treated with cediranib had
      lower relative VEGFR-2 plasma concentrations and tumor burdens. In conclusion,
      cediranib showed potent antitumor and antiangiogenic efficacy in the RENCA model.
      sVEGFR-2 plasma concentrations can act as a surrogate marker for antitumor
      activity of VEGFR signaling inhibitors.

PMID- 20044619
TI  - Autophagy: novel action of panitumumab in colon cancer.
AB  - BACKGROUND: Panitumumab, a fully-human monoclonal antibody raised against
      epidermal growth factor receptor (EGFR), has been approved by the U.S. Food and
      Drug Administration (FDA) and the European Medicines Agency (EMEA) for the
      treatment of patients with EGFR-expressing metastatic colorectal carcinoma (mCRC)
      after failure of standard chemotherapy. Additionally, the guideline of the EMEA
      includes the use of panitumumab in patients with wild-type KRAS. The goal of the
      current study was to evaluate the effect of panitumumab on colon cancer cells,
      proliferation, apoptosis, necrosis, cell cycle arrest and autophagy. The effect
      of panitumumab on the redox status of the cells was also studied. MATERIALS AND
      METHODS: The cell lines Caco-2, DLD-1 and HT-29 which differ in their expression
      of EGFR and HER-2 were used. Cell proliferation and apoptosis/necrosis were
      measured by methyl tetrazolium (MTT) assay and annexin V/propidium iodide assay,
      respectively. Cell cycle arrest was estimated by propidium iodide assay and
      autophagy was detected using Western blot analysis. Spectrophotometrical
      quantification of glutathione (GSH) levels and an analysis of KRAS sequence were
      applied. RESULTS: Panitumumab reduced proliferation only in the DLD-1 cells
      despite the mutated KRAS in this cell line. However, panitumumab did not affect
      DLD-1 cell apoptosis, necrosis or cell cycle progression. Interestingly,
      immunoblotting analysis revealed that panitumumab increased protein levels of
      beclin-1, a marker of autophagy. In addition, an increase in the GSH level was
      noted following panitumumab treatment reflecting an imbalance in the redox status
      of the cells. CONCLUSION: Panitumumab affects colon cancer cell proliferation
      independently of KRAS mutations and EGFR protein levels, possibly through the
      induction of autophagy.

PMID- 20044620
TI  - Non-apoptotic cell death induced by nutritional starvation in J774.1 mouse
      macrophage-like cell line.
AB  - The growth and amino acid utilization of a mouse macrophage-like cell line J774.1
      was investigated in two different culture media supplemented with 10% fetal
      bovine serum (FBS). The J774.1 cells grew faster, and consumed glutamine and
      serine at higher rates in DMEM than in RPMI1640 medium. The consumption of other
      amino acids was much less, while considerable quantities of alanine, glutamic
      acid and glycine were produced by the J774.1 cells. When the cells became
      confluent, serine, but not glutamine, was nearly depleted from the culture
      medium, followed by cell death characterized by smear DNA fragmentation, slight
      caspase-3 activation and structural damage of the mitochondria. Serine is
      required for the growth of mouse macrophage-like cell lines, and DMEM is superior
      to RPMI1640 for long-term cell culture.

PMID- 20044621
TI  - Regulating immunity and inhibiting tumor growth by the recombinant peptide sPD-1
      CH50.
AB  - BACKGROUND: Soluble programmed death-1 (sPD-1) has been proven to bind PD-1
      ligands (PD-Ls), block PD-L/PD-1 interactions, and enhance the cytolysis of
      cytotoxic T-lymphocytes (CTLs). CH50, a two-domain molecule of fibronectin, has
      been shown to suppress the development of tumors via enhancing the activity of
      macrophages. This study evaluated the influence of the recombinant peptide sPD-1
      CH50 on antitumor immunity. MATERIALS AND METHODS: A secretory recombinant
      peptide, sPD-1-CH50, containing three functional domains was constructed, and its
      antitumor effect and mechanism were studied. RESULTS: The data demonstrated that
      sPD-1-CH50 was able to increase the cytolytic activity of both macrophages and
      CTLs, especially towards B7-H1-positive tumor cells. The effect correlated with
      the enhanced production of inducible nitric oxide synthase (iNOS), tumor necrosis
      factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma). In vivo studies
      showed that sPD-1-CH50 inhibited the invasiveness and growth of hepatoma.
      CONCLUSION: Regulation of immune cells by sPD-1-CH50 has potential therapeutic
      value for the inhibition of invasion and growth of hepatoma.

PMID- 20044622
TI  - Lung tumor growth is stimulated in IFN-gamma-/- mice and inhibited in IL-4Ralpha
      /- mice.
AB  - BACKGROUND: Alternative (M2) macrophage activation is associated with tumor
      development in many tumor types, including those in the lung. Herein the
      biological consequences of forcing classical (M1) or alternative (M2) macrophage
      activation on lung tumor development are examined. MATERIALS AND METHODS:
      Urethane-induced lung tumor multiplicity and size were compared in IFN-gamma(-/-)
      mice which lack M1 macrophage activation, IL-4Ralpha(-/-) mice which lack M2
      macrophage activation, and wild-type BALB/cJ (background strain of the IFN-gamma(
      /-) and IL-4Ralpha(-/-) mice) mice. Tumor-associated macrophage (TAM) and bone
      marrow-derived monocyte (BDMC) activation were each examined. RESULTS: The TAMs
      and BDMCs in the IFN-gamma(-/-) mice exhibited M2 activation, and their lung
      tumors were significantly larger than those in the wild-type mice. In contrast,
      urethane-treated IL-4Ralpha(-/-) mice, whose TAMs and BDMCs were M1 activated,
      developed smaller tumors than the wild-type mice. CONCLUSION: Altered innate
      immunity can diminish or accelerate lung tumor progression in response to
      defective cytokine signaling.

PMID- 20044623
TI  - Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma
      xenografts through an antiangiogenic mechanism.
AB  - Chitosan nanoparticles (CNP) have demonstrated anticancer activity in vitro and
      in vivo by a few recent researches. However, the mechanisms involved in their
      potential anticancer activity remain to be elucidated. In this study, the effects
      of CNP on tumor growth were investigated using a model of nude mice xenografted
      with human hepatocellular carcinoma (HCC) (BEL-7402) cells. The results
      demonstrated that the treatment of these nude mice with CNP significantly
      inhibited tumor growth and induced tumor necrosis. Furthermore, microvessel
      density (MVD) determination by counting immunohistologically stained tumor
      microvessels suggested that CNP dose-dependent tumor suppression was correlated
      with the inhibition of tumor angiogenesis. Mechanistically, immunohistochemical
      and quantitative real-time reverse transcription-polymerase reaction assays
      provided evidence that CNP-mediated inhibition of tumor angiogenesis was linked
      to impaired levels of vascular endothelial growth factor receptor 2 (VEGFR2). Due
      to their low or non-toxicity, CNP and their derivatives may represent a novel
      class of anti-cancer drug.

PMID- 20044624
TI  - Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early
      breast cancer.
AB  - BACKGROUND: The prognostic role of serum levels of molecular biomarkers during
      the perioperative period in patients with early breast cancer is not clear.
      PATIENTS AND METHODS: Serum VEGF and extracellular domains (ECD) of EGFR and HER2
      were prospectively determined in 119 consecutive patients with early breast
      cancer on the day before and after surgery. RESULTS: After a median follow-up of
      93 months, the preoperative value and the absolute change from pre- to
      postoperative serum levels of VEGF and HER2 ECD did not predict disease-free
      survival (DFS). A decrease after surgery of EGFR ECD correlated with a
      statistically significant lower DFS; each 1 ng/ml decrease in EGFR ECD serum
      level was associated with an increase of event risk of 15% on multivariable
      analysis (hazard ratio 1.15 95% confidence interval 1.04.-1.28, p=0.006).
      CONCLUSION: The perioperative absolute change of EGFR ECD significantly
      correlated with disease outcome of patients with early breast cancer. No
      correlation was found between preoperative and perioperative absolute change of
      serum VEGF and HER2 ECD.

PMID- 20044625
TI  - Significant association of ERCC6 single nucleotide polymorphisms with bladder
      cancer susceptibility in Taiwan.
AB  - AIM: To evaluate the association between the polymorphisms of the ERCC6 DNA
      repair gene, which plays an important role in maintaining genome stability, and
      the risk of bladder cancer in Taiwan. MATERIALS AND METHODS: In this hospital
      based case-control study, the association of ERCC6 codon 399, 1097 and 1413
      polymorphisms with bladder cancer risk in a Central Taiwanese population was
      first investigated. In total, 288 patients with bladder cancer and 288 age- and
      gender-matched healthy controls recruited from the China Medical Hospital in
      Taiwan were genotyped. RESULTS: A significantly different distribution was found
      in the frequency of the ERCC6 codon 399 genotypes, but not the ERCC6 codon 1097
      or 1413 genotypes, between the bladder cancer and control groups. Those who had
      homozygous A/A or heterozygous A/G at ERCC6 codon 399 showed a 1.97- and 1.04
      fold (95% confidence interval=1.29-3.01 and 0.71-1.53, respectively) increased
      risk of bladder cancer compared to those with G/G. As for ERCC6 codon 1097 or
      1413, there was no difference in distribution between the bladder cancer and
      control groups. CONCLUSION: The first evidence that the homozygous A allele of
      the ERCC6 codon 399 may be associated with the development of bladder cancer and
      may be a novel useful marker for primary prevention and anticancer intervention
      is provided.

PMID- 20044626
TI  - Diagnostic and therapeutic relevance of NY-ESO-1 expression in oral squamous cell
      carcinoma.
AB  - BACKGROUND: Cancer/testis antigen 1B (NY-ESO-1) is exclusively expressed in
      various types of tumor but not in healthy normal tissue, except testis, and
      induces strong cellular and humoral immune responses. Therefore, it represents an
      ideal target for diagnostic and immunotherapeutic applications. The aim of the
      study was to investigate the expression of NY-ESO-1 in oral squamous cell
      carcinoma (OSCC) to determine its impact as a diagnostic parameter or a
      therapeutic target for oral cancer. PATIENTS AND METHODS: A total of 65 OSCC and
      20 normal oral mucosal samples of otherwise healthy volunteers were included in
      this study. Expression of NY-ESO-1 was determined using reverse transcriptase
      polymerase chain reaction (RT-PCR). The results were correlated to diagnosis and
      clinicopathological parameters. RESULTS: NY-ESO-1 was expressed in 27.7% of the
      investigated tumor samples, but not in normal oral mucosal. The correlation
      between NY-ESO-1 expression and malignancy was significant (p=0.008). The
      prevalence of NY-ESO-1 expression was significantly associated with tumor size
      (p=0.033), but not with histological grading, positive lymph node status or
      clinical stage of disease. CONCLUSION: NY-ESO-1 expression is restricted to OSCC,
      clearly indicating malignancy. However, the expression rate of this antigen is
      too low for clinical application but it might be a useful additional biomarker
      within a multiple marker system for the diagnosis of OSCC. In addition, NY-ESO-1
      might be a candidate for immunotherapy and polyvaccination in patients suffering
      from OSCC.

PMID- 20044627
TI  - DNA repair gene XRCC1 polymorphisms and outcome of renal cell carcinoma in
      Caucasian patients.
AB  - BACKGROUND: The human X-ray repair cross-complementing group 1 (XRCC1) enzyme
      plays an important role in response to DNA damage. Two common polymorphisms in
      XRCC1, Arg194Trp and Arg399Gln, have been repeatedly associated with risk for and
      outcome of numerous types of cancer treated with radio- and chemotherapy.
      Recently, a Japanese study suggested these polymorphisms both as risk factors and
      outcome predictors in renal cell carcinoma (RCC). PATIENTS AND METHODS: In the
      present study, 142 Caucasian patients suffering from RCC were genotyped and
      analyzed for tumor-related and overall survival and time to metastasis and
      progression. RESULTS: Analyses revealed absence of the pre-described risk
      haplotype (194Trp/399Gln) as well as a lack of a statistically significant
      difference between the different endpoints and genotypes and diplotypes,
      respectively. CONCLUSION: We conclude that in Caucasian patients, XRCC1
      polymorphisms do not influence the outcome of RCC.

PMID- 20044628
TI  - Docetaxel, ifosfamide and cisplatin (DIP) in squamous cell carcinoma of the head
      and neck.
AB  - BACKGROUND: Docetaxel, ifosfamide and cisplatin have all shown activity in
      squamous cell carcinoma of the head and neck (SCCHN). The optimal combination of
      the three drugs is, however, unknown. Considering the favorable results of taxane
      containing triplets as induction chemotherapy in locally advanced (LA) SCCHN, DIP
      (docetaxel, ifosfamide, cisplatin) was studied in this setting as part of a phase
      I dose- and sequence-exploring study. PATIENTS AND METHODS: D (60 or 75 mg/m(2))
      was given by 60-min infusion on day 1, I (1000 mg/m(2)/day), with mesna until 12
      hours after I, by 24-h infusion days 1-5, and P (50 or 75 mg/m(2)) by 24-h
      infusion on days 1 or 5. The cycles were repeated every 21 days. Toxicities
      according to the National Cancer Institute Common Toxicity Criteria version 2
      (NCI-CTC2) were evaluated weekly and response was evaluated every 2 cycles
      according to the World Health Organization (WHO) criteria. Thereafter,
      radiotherapy (RT, cumulative dose 70 Gy) or chemoradiation (CRT), both with
      conventional fractionation, were planned. RESULTS: Twenty-two patients (18 male,
      4 female; age 41-66 years, performance status 0-1, 2 T4N0, 3 T3N2, 11 T4N2, 3 T
      unknown N3, 1 T1N3 and 2 T4N3) received a median of 4 DIP cycles (range 1-5).
      Grade 4 neutropenia occurred in 18 patients, grade 3 and 4 thrombocytopenia in 5
      and 1 patients, respectively, and grade 3 anemia in 5 patients. Gastrointestinal
      and mucosal toxicities were generally mild/moderate. Vascular complications
      (probably not DIP-related) precluded local treatment in two patients. Moreover,
      one patient died on day 13 of the first DIP (neutropenic sepsis and myocardial
      infarction). The remaining patients received RT (n=2) or CRT (n=17; 16 of these
      with gemcitabine). The response to 2 x DIP was 95% (1 complete response, 19
      partial responses, 1 stable disease); the complete response rate increased to 42%
      after 4 x DIP. No dose or sequence effect was evident. The minimum follow-up of
      the surviving patients was 51 months, with median relapse-free survival of 13.8
      months and median overall survival of 18.8 months. Only four patients relapsed at
      distant sites. CONCLUSION: DIP is highly active in previously untreated LA SCCHN,
      however, toxicity of DIP in this population is substantial.

PMID- 20044629
TI  - Statins and breast cancer in postmenopausal women without hormone therapy.
AB  - BACKGROUND: Epidemiological data on the association between statin use and risk
      of breast cancer among overweight or obese postmenopausal women who have never
      used hormone therapy (HT) is limited. PATIENTS AND METHODS: A hospital-based case
      control study was conducted in Fargo, ND, USA. Cases were overweight or obese,
      postmenopausal White women without a history of HT use who were newly diagnosed
      with breast cancer. Controls were White women without clinical cancer who were
      seen at the same hospital for an annual physical examination. RESULTS: From a
      patient population aged 55 to 81 years old, data were obtained on 95 cases and 94
      controls. Overall, there was no association between the use of statins and breast
      cancer risk odds ratio (OR)=1.3 (95% confidence interval (CI) 0.7-2.5). However,
      risk varied by hormone receptor status. Compared to non-users, obese women who
      used hydrophobic statins had an elevated risk of progesterone receptor-negative
      (PR(-)) breast cancer OR=4.0 (95% CI 1.2-13.8), but not of tumors with other
      hormone receptor profiles. The risk for breast cancer was also significantly
      increased among overweight women who used hydrophobic statins for less than or
      equal to 4 years OR=4.1 (95% CI 1.2-14.4). CONCLUSION: This observational study
      found an increased risk of breast cancer related to duration of statins use and
      PR(-) among postmenopausal women.

PMID- 20044630
TI  - Phase I dose escalation study of gemcitabine plus irinotecan in advanced solid
      tumors.
AB  - AIM: To determine the maximally tolerated dose (MTD), recommended phase II dose
      (RPTD) and toxicity profile of gemcitabine plus irinotecan combination. PATIENTS
      AND METHODS: Thirty-nine evaluable patients with advanced solid tumors were
      treated with gemcitabine (Gem) and irinotecan (Iri) on days 1, 8 and 15 of a 28
      day cycle. Dose levels included Gem/Iri 700/50, 900/50, 900/75, 500/50 mg/m(2)
      respectively. Dose-limiting toxicity (DLT) was assessed during cycle one;
      toxicity evaluation was closely monitored throughout the course of treatment.
      Treatment continued until disease progression or unacceptable toxicity. RESULTS:
      DLTs primarily consisted of grade > or = 3 thrombocytopenia lasting > or = 4 days
      often accompanied by grade > or = 3 neutropenia. Other grade > or = 3 toxicities
      included vomiting, diarrhea, fatigue and elevated alkaline phosphatase. Three
      patients had a partial response. Stable disease as best response was seen in 16
      patients, ranging from 2-18 months. CONCLUSION: The MTD/RPTD is gemcitabine 500
      mg/m(2) plus irinotecan 50 mg/m(2) on days 1, 8 and 15 of a 28-day cycle. Given
      the toxicity profile and negative results of phase III studies, no further
      testing of this treatment combination is recommended.

PMID- 20044631
TI  - Pathology of prostate cancer and focal therapy ('male lumpectomy').
AB  - Focal therapy of the prostate is defined as prostate gland ablation aiming at
      eradication of unifocal low-risk prostate cancer, and preserving uninvolved (peri
      ) prostatic tissue and therefore quality of life. The major arguments against
      focal therapy can be classified under the headings of understaging and
      multifocality. The argument of understaging highlights the importance of the
      occasional, but troublesome, finding of a large, extraprostatic or high-grade
      tumor (Gleason score > or = 7) in about a quarter of radical prostatectomy
      specimens removed from men initially classified as having a low-risk tumor.
      Indeed, 85% of all prostate cancer cases are multifocal. These concerns can be
      offset by additional testing: another biopsy, especially a transperineal mapping
      biopsy, and magnetic resonance imaging (MRI) of the prostate. The technology
      needed to ablate small regions or sectors of the prostate harboring a known
      cancer is rapidly becoming available. Cryotherapy is already being used and the
      preliminary data are encouraging, Ultrasound-guided high-intensity focused
      ultrasound (HIFU), photodynamic therapy using newly developed light-sensitizing
      agents, and MRI-guided HIFU are all promising new tools.

PMID- 20044633
TI  - Chemotherapy for glioblastoma: current treatment and future perspectives for
      cytotoxic and targeted agents.
AB  - Glioblastoma is the most frequent and devastating primary malignant brain tumor
      in adults. Surgery followed by standard radiotherapy with concomitant and
      adjuvant chemotherapy with temozolomide is the standard of care in patients with
      glioblastoma, however the prognosis remains poor with a median survival in the
      range of 12-15 months. Common genetic abnormalities in glioblastoma are
      associated with aberrant activation or suppression of cellular signal
      transduction pathways and resistance to radiation and chemotherapy. Special
      attention has been focused on targets such as epidermal growth factor receptor,
      vascular endothelial growth factor receptor, platelet-derived growth factor
      receptor, and on pathways such as the phosphatidylinositol-3kinase/Akt/mammalian
      target of rapamycin and Ras/Raf/mitogen-activated protein-kinase pathways.
      Several signal transduction inhibitors have been examined in preclinical and
      clinical malignant glioma trials, including antiangiogenic agents (bevacizumab,
      enzastaurin), and inhibitors of epidermal growth factor receptor tyrosine kinase
      (gefitinib and erlotinib), mammalian target of rapamycin (temsirolimus,
      everolimus) and integrin (cilengitide). Although preliminary clinical results of
      the use of targeted agents have not translated into significantly better
      survival, more recent phase II trials are exploring the combination of
      multitargeted drugs with cytotoxic chemotherapy and radiotherapy in order to
      overcome the resistance of tumors to single-agent targeted therapies. This review
      summarizes the current results with cytotoxic and targeted molecular agents in
      glioblastoma and the development of new chemoradiation strategies under
      evaluation to increase their effectiveness.

PMID- 20044632
TI  - Increased incidence of papillary thyroid cancer detection among thyroidectomies
      in Greece between 1991 and 2006.
AB  - OBJECTIVE: To examine existing evidence, trends and possible factors that may
      have affected the incidence of papillary thyroid cancer (PTC) among patients
      undergoing thyroidectomies in an iodine-sufficient population of Greece. STUDY
      DESIGN: All histology records from the patients who had undergone thyroid surgery
      at the Department of Surgery Laiko Hospital, Athens, Greece from January 1991 to
      December 2006 were retrospectively analyzed. Records were placed in a database
      which included patients' demographics, history, and medical condition, clinical
      and surgical parameters. PATIENTS AND METHODS: One thousand four hundred and
      twenty-six patients (265 males and 1161 females) had undergone thyroidectomy
      during the above period of time. All surgeons favoured total thyroidectomy with
      resection of pro- and paratracheal lymph nodes. Thyroid tumors were classified
      according to the WHO classification system and were staged according to the TNM
      staging system. RESULTS: In 278 patients, PTC was histologically diagnosed. From
      1999 onwards, thyroid surgery shifted towards total thyroidectomy, while
      statistically significantly increased incidence of PTC and papillary
      microcarcinoma detection and decreased incidence of PTC greater than 10 mm
      detection in the whole population were noticed. Moreover, from 1999 onwards,
      smaller size of primary tumors, higher incidence of T1 tumors, lower incidence of
      T4 tumors, lower incidence of metastatically infiltrated peritracheal lymph
      nodes, higher incidence of stage I tumors and lower incidence of stage IV tumors
      were documented. Finally, a higher incidence of PTC in males, females and the
      whole population aged 51-70 years compared to the other age groups since 2003 was
      noticed. CONCLUSION: The increased incidence of PTC clearly correlated to the
      increased incidence of papillary microcarcinoma detection, reflecting the
      proportion for total thyroidectomy as well as changes in the diagnostic approach
      boosted by more careful pathological examination, rather than the effect of
      environmental factors such as the Chernobyl accident. Whether the Chernobyl
      accident has any predisposing effect on the increased incidence of PTC remains to
      be proven.

PMID- 20044634
TI  - Claudin-5 overexpression correlates with aggressive behavior in serous ovarian
      adenocarcinoma.
AB  - BACKGROUND: Claudins are essential tight junctional proteins between adjacent
      epithelial, mesothelial or endothelial cells, and are responsible for the
      permeability of the paracellular space. The expression of claudin-5 and its
      correlation to ovarian cancer behavior was investigasted. MATERIALS AND METHODS:
      A total of 85 serous ovarian cancer tissue samples were analyzed using
      immunohistochemical staining. RESULTS: An association between claudin-5
      expression and cancer grade (p=0.016) and advanced stage (p=0.022), strongest
      claudin-5 expression was found in advanced stage and high-grade carcinomas. An
      association between claudin-5 expression and cancer-specific (p=0.032) and
      overall survival (p=0.026) was also found. Only 25-30% of claudin-5-positive
      patients, but 60% of claudin-5-negative patiens were alive at the 5-years follow
      up. CONCLUSION: Increased claudin-5 expression is associated with aggressive
      behavior in serous ovarian adenocarcinoma.

PMID- 20044635
TI  - Neoplastic meningitis from breast cancer: feasibility and activity of long-term
      intrathecal liposomal Ara-C combined with dose-dense temozolomide.
AB  - BACKGROUND: Patients with neoplastic meningitis (NM) from breast cancer have a
      median survival of 4-8 months with specific treatment. Here, good tolerance and
      long-term stabilization with combined intrathecal liposomal cytarabine (Ara-C),
      which is probably the most promising drug for intrathecal chemotherapy to date,
      near-continuous temozolomide and radiotherapy is reported in two patients with
      leptomeningeal and solid central nervous system (CNS) metastases from breast
      cancer. CASE REPORTS: A 42- and a 43-year-old female presented with NM and
      disseminated CNS metastases from human epidermal growth factor receptor type 2
      (Her2)-positive breast cancer. After irradiation of the symptomatic sites,
      intrathecal liposomal Ara-C every 2-4 weeks was combined with temozolomide 100
      mg/m(2) day 1-5/7. Cerebrospinal fluid (CSF) cytology and neurological symptoms
      improved in both patients and stabilized for several months. The patients
      survived 10 and 17 months after diagnosis of NM, without signs of neurological
      toxicity. CONCLUSION: Intensive treatment is complicated by extensive pre
      treatment and the lack of active CNS-penetrating systemic drugs. The long-term
      results with up to 17 intrathecal injections of liposomal Ara-C show that this
      treatment regimen is feasible and well-tolerated. The stabilization of both
      patients indicates activity of this combined intrathecal and systemic regimen
      that is based on long-term exposure of the tumour cells to both Ara-C and
      temozolomide. The results need to be confirmed prospectively.

PMID- 20044636
TI  - Extraskeletal osteosarcoma with partial spontaneous regression.
AB  - Resection for a mass in the proximal thigh was performed on a 57-year-old woman,
      the diagnosis of which was extraskeletal osteosarcoma. In pathological findings,
      tumor cells gradually decreased from the central area of the mass composed of
      spindle cell sarcoma and were replaced by fibrocollagenous tissue with no sarcoma
      cells. CD8(+), T-cell-restricted intracellular antigen-1 (TIA-1)(+), granzyme
      B(+) T lymphocytes appeared to infiltrate the mass lesion, so that we hypothesize
      that the immunological system was likely to be involved via T lymphocytes in
      triggering spontaneous regression in this case. One of the most unusual phenomena
      in cancer biology is the spontaneous regression of a tumor. Here, we report on
      the first case of extraskeletal osteosarcoma characterized by partial spontaneous
      regression of the primary lesion.

PMID- 20044637
TI  - A novel strategy by cryoablation for advanced hepatoma.
AB  - Ablative techniques have been developed against advanced liver cancer in cases
      where surgical resection is impossible. Among the ablation procedures used,
      thermal ablation therapy is widely applied, and the safety and efficacy of this
      technique in controlling local progression of cancer have been well
      characterized. However, the principle of cryosurgery is not only to control local
      recurrence, but also to stimulate the immune system into initiating an antitumor
      response. In recent years, we have used a liquid nitrogen-based cryogenic
      procedure and developed a treatment method for patients with unresectable liver
      tumors. Following this, repeated treatment was demonstrated to induce anticancer
      immune reaction-related factors. In the present study, a novel strategy as a
      cryoablation-induced anti-cancer immune reaction is introduced.

PMID- 20044638
TI  - Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and
      convenient regimen for advanced pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer remains a disease of high mortality and one of the
      most frustrating, resistant solid neoplasms to treat. The aim of this study was
      to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with
      advanced (stage III-IV) pancreatic cancer in terms of overall survival and time
      to progression of the disease. The secondary aim was to record treatment related
      toxicities. PATIENTS AND METHODS: Twenty-seven patients with metastatic non
      operable pancreatic adenocarcinoma, stage III-IV, consented to receive
      chemotherapy with gemcitabine and erlotinib. Patients received first-line
      treatment with gemcitabine (2 g/m(2) via 90 min i.v. infusion every two weeks)
      and 100 mg erlotinib per os every day, for at least 12 consecutive courses (6
      cycles). Treatment was discontinued at disease progression and/or serious
      toxicity. RESULTS: The objective response rate was 25.9% (95% confidence interval
      [CI]: 11.1-46.3%) and the stable disease rate was 59.3% (95% CI: 38.8-77.6%). The
      one-year overall survival was 20%. The median overall survival and time to
      progression at the time of assessment was 7.5 months (95% CI: 3.6-42 months) and
      5.5 months (95% CI: 1.5-10 months), respectively. Overall survival and time to
      progression were related to response (p<0.001), while time to progression was
      further related to disease stage (p=0.011). No grade 4 haematological or non
      haematological toxicities were observed. CONCLUSION: The biweekly regimen of
      gemcitabine plus erlotinib has similar toxicity and efficacy to weekly
      administration, presenting both patients and hospital resource departments with a
      clearly more convenient therapy alternative.

PMID- 20044639
TI  - Concurrent versus sequential chemotherapy and radiotherapy in limited disease
      small cell lung cancer: a retrospective comparative study.
AB  - BACKGROUND: Patients with limited-disease small cell lung cancer are treated with
      chemotherapy and chemotherapy combined with radiotherapy. Treatment schemes with
      curative intention include sequential or concurrent chemoradiotherapy, both
      combined with prophylactic cranial irradiation (PCI). It is unclear which scheme
      is superior. PATIENTS AND METHODS: Until 2001, patients received 4-5 cycles of
      chemotherapy. In cases of no complete response, palliative radiotherapy (RT) was
      given in 13 fractions of 3 Gy (CT-RT group, N=26). A total of 89 patients did not
      receive RT after chemotherapy (CT group). After complete response, curatively
      intended RT was given, of 16x2.5 Gy, concurrently with PCI of 15x2 Gy (SCT-RT
      group, N=111). From 2001, 40 patients received 4-5 cycles of chemotherapy
      concurrently with RT of 25x1.8 Gy. PCI was applied to patients with complete
      response (CCT-RT group). Endpoints were median survival time (MST) and overall
      survival (OS). RESULTS: MST of CT, CT-RT, SCT-RT and CCT-RT were 8.1, 12.5, 14.0
      and 21.8 months, and 5-year OS 3.5, 4.8, 10.5 and 26.9%, respectively.
      Frequencies of brain metastasis after PCI in SCT-RT and CCT-RT patients were
      16.4% and 8.7%, respectively. CONCLUSION: Concurrent chemoradiotherapy resulted
      in longer MST and higher OS than sequential chemoradiotherapy, chemotherapy with
      palliative radiotherapy or chemotherapy alone. Results may improve further by
      applying PCI at an earlier stage and increasing the RT dose.

PMID- 20044640
TI  - Tyrosine kinase inhibitor-induced macrocytosis.
AB  - BACKGROUND: The tyrosine kinase inhibitors (TKI) sunitinib and imatinib were
      shown to induce macrocytosis in patients with renal cell cancer (RCC) and
      gastrointestinal stromal tumors (GIST), presumably through inhibition of the c
      KIT dependent signaling pathway of erythroid progenitor cells of the bone marrow.
      PATIENTS AND METHODS: Hematology charts of patients with RCC, breast cancer (BC),
      GIST, non-small cell lung cancer (NSCLC) and hepatocellular cancer (HCC),
      receiving single-agent sunitinib, imatinib, sorafenib, erlotinib and BI 2992
      (Tovok) at the recommended dose for at least 3 months were reviewed
      retrospectively for the occurrence of macrocytosis. RESULTS: Macrocytosis
      occurred in all patients with RCC and BC treated with sunitinib and in all
      patients with GIST treated with imatinib. The percentage increase of the mean
      corpuscular volume (MCV) of peripheral red blood cells (RBC) compared with
      baseline at 3, 6, 9 and 12 months was 12.4%, 16.8%, 16.6%, 12.7% and 0.7%, 5.6%,
      5.9%, 5% with sunitinib and imatinib respectively. The values at 3, 6 and 9
      months between both groups were significantly different. Sorafenib, erlotinib and
      BI 2992 did not induce macrocytosis. CONCLUSION: Sunitinib-induced macrocytosis
      was not confined to patients with RCC alone but also occurred in patients with
      BC. Imatinib also induced macrocytosis in patients with GIST but to a
      significantly lower degree. Because both drugs were used at an effective
      pharmacodynamic dose inhibiting c-KIT, these data strongly suggest that pathways
      in addition to c-KIT and not common to both agents are involved in the TKI
      induced macrocytosis.

PMID- 20044641
TI  - Central adiposity as a major risk factor of ovarian cancer.
AB  - The identification of risk factors for ovarian cancer is crucial in prevention of
      the disease. This pathology is the leading cause of death from gynecological
      malignancies. The aim of this study was to evaluate the role of factors
      influencing hormonal levels such as body mass index (BMI), BMI at age 20, waist
      to-hip ratio (WHR), oral contraceptive (OC) use, and risk of ovarian cancer. A
      case-control study was conducted in women who developed ovarian cancer. Logistic
      regression was used to calculate the odds ratio (OR) and 95% confidence interval
      (95% CI). While no association was found between BMI, BMI at age 20 and risk of
      ovarian cancer, high WHR increased the risk with ORs of 2.93 and 8.58 (p<10(-6))
      for the highest categories (WHR=0.801-0.85 and WHR>0.85) versus the lowest
      (WHR<0.8). Central adiposity is a key factor in ovarian cancer and suggests the
      involvement of androgen conversion in adipose tissue.

PMID- 20044642
TI  - Phase II trial of the association of a methionine-free diet with cystemustine
      therapy in melanoma and glioma.
AB  - BACKGROUND: In a previous phase I clinical trial of dietary methionine (MET)
      restriction with cystemustine treatment for melanoma or glioma, we determined the
      optimal MET-free diet duration to be 1 day. On this basis, a phase II clinical
      trial was initiated to evaluate safety and efficacy of this combination. PATIENTS
      AND METHODS: Twenty-two patients (20 with metastatic melanoma and 2 with
      recurrent gloma) received a median of 4 cycles of the association of a 1-day MET
      free diet with cystemustine (60 mg/m(2)) every two weeks. RESULTS: This
      association was well tolerated (toxicity and nutritional status). Toxicity
      remained mainly hematological and consisted of WHO grade 3-4 thrombocytopenia,
      leucopenia and neutropenia in 36, 27 and 27% of patients respectively. The median
      disease-free survival was 1.8 months and the median survival was 4.6 months, with
      2 long-duration stabilizations. The plasmatic MET depletion obtained was of 40 +
      or - 31%.

PMID- 20044643
TI  - Low-dose IL-2 therapy reduces HCV RNA and HBV DNA: case report.
AB  - BACKGROUND: Patients with concomitant hepatitis C (HCV) and B (HBV) infection are
      difficult to treat due to lack of medicines that control these viral infections
      and the high risk of hepatocellular carcinoma. Currently, there are insufficient
      data regarding the therapeutic effect of interleukin-2 (IL-2) during chronic
      viral infection, but this cytokine has shown antineoplastic activity and may have
      also an antiviral effect. CASE REPORT: We present the case of a 44-year-old
      patient with hemophilia A, HBV and HCV related compensated liver cirrhosis (Child
      Pugh A) with several zones in the liver, highly suspicious for hepatocellular
      carcinoma. The patient was treated with low-dose intermittent subcutaneous IL-2
      immunotherapy, followed by standard therapy with pegasys and copegus. During 23
      months' follow-up, no tumour progression occurred, and the patient remained in
      Child-Pugh A stage. The initial HCV and HBV loads were significant (538,207
      IU/ml) and minimal (825 copies/ml), respectively. The patient was treated with
      intermittent subcutaneously applied low-dose IL-2 cycles for ten months. HBV DNA
      and HCV RNA were undetectable 3 months after the last IL-2 cycle. After cessation
      of IL-2 therapy, the patient received standard antiviral treatment with pegasys
      and copegus. Nine months later, a slight reactivation of viruses was observed:
      HBV DNA was 18,600 copies/ml and HCV RNA was 58 IU/ml. Twenty-three months after
      the last IL-2 treatment (at the time of writing), the patient is alive and in a
      good clinical condition. CONCLUSION: The decrease of HBV and HCV nucleic acids
      during immunotherapy with IL-2 predicts a possible new therapeutic option for
      these chronic viral infections.

PMID- 20044644
TI  - Routine use of pamidronate in NSCLC patients with bone metastasis: results from a
      retrospective analysis.
AB  - BACKGROUND: No data on the tolerability and effects of pamidronate in non-small
      cell lung cancer patients with bone metastasis are available. We performed a
      retrospective analysis to evaluate the routine use of pamidronate in these
      patients. PATIENTS AND METHODS: One hundred and four patients with NSCLC were
      treated at our Day Hospital between May 2003 and February 2009. Forty-one (39.5%)
      presented with bone metastasis during the course of the disease. Thirty (73.2%)
      of these patients received pamidronate at a dose of 90 mg every four weeks.
      RESULTS: The occurrence of bone metastasis was associated with a poor overall
      survival, but patients treated with pamidronate had a significantly better median
      overall survival than untreated patients (15.4 months vs. 2.1 months; p<0.001).
      Pamidronate was well tolerated and only grade 1 or 2 toxicities were registered.
      CONCLUSION: The diagnosis of bone metastasis and the consequent routine
      administration of pamidronate have an impact on survival of NSCLC patients; this
      drug is a good candidate for routine use in haemato-oncological centres.

PMID- 20044645
TI  - Significant association of DNA repair gene Ku80 genotypes with breast cancer
      susceptibility in Taiwan.
AB  - AIM: To evaluate the association between the genotypes of the heterodimeric DNA
      binding component, Ku80 gene and the breast cancer risk in Taiwan. PATIENTS AND
      METHODS: In this hospital-based case-control study, the association of Ku80 G
      1401T rs828907, Ku80 C-319T rs11685387 and Ku80 intron19 rs9288518 polymorphisms
      with breast cancer risk in a Taiwanese population was investigated. In total,
      1272 patients with breast cancer and the same number of age- and gender-matched
      healthy controls were genotyped. RESULTS: A significantly different distribution
      was found in the frequency of the Ku80 G-1401T genotype, but not the Ku80 C-319T
      or intron 19 genotypes, between the breast cancer and control groups. The T
      allele Ku80 G-1401T conferred a significant (p=0.0069) increased risk of breast
      cancer. Gene interactions with smoking, but not with breastfeeding, were
      significant for the Ku80 G-1401T polymorphism. The Ku80 G-1401T GT and TT
      genotypes in association with smoking conferred an increased risk of 3.162 (95%
      confidence interval=2.275-4.393) for breast cancer. CONCLUSION: The T allele of
      Ku80 G-1401T may be associated with the development of breast cancer and may be a
      novel useful marker for breast cancer detection and prediction.

PMID- 20044646
TI  - FNA cytology and frozen section examination in patients with follicular lesions
      of the thyroid gland.
AB  - Patients with solitary thyroid nodules should have fine-needle aspiration (FNA)
      cytology as the initial screening test, but the most of those referred to a
      surgeon usually undergo frozen section examination (FS). The aim of this
      retrospective study was to assess the usefulness of FNA cytology and FS together
      in patients with a solitary thyroid nodule (TN). Two-hundred and ten patients
      with a TN and FNA cytology suggesting follicular neoplasm underwent
      intraoperative FS and subsequent hemithyroidectomy or total thyroidectomy. There
      were 47 (22.4%) men and 163 (77.6%) women, with a median age of 43 years (range
      18-76 years). In all patients, ultrasound-guided FNA was successfully performed
      using 22-G needle prior to surgery. Smears of the FNA samples were stained by May
      Grunwald-Giemsa stain and evaluated immediately by the cytologist. Final
      histology was follicular carcinoma in 23 (10.9%), follicular adenoma in 181
      (86.2%), and hyperplasia in 6 (2.9%) patients. No difference (p=NS) in age of the
      patients, and greatest diameter on the TN was found between groups. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy were 13.0%, 97.3%, 37.5%, 90.0%, and 88.1% for FNA cytology, and
      17.4%, 100%, 100%, 90.8%, and 91.0% for FS, respectively. The combination of FNA
      plus FS did not significantly improve the results. In conclusion, both FNA
      cytology and FS are highly specific tests, but their sensitivity is low, even
      when they are used in combination. Thus, in patients with smears suggesting
      follicular neoplasm, FS should be considered unnecessary because it does not
      affect the intraoperative decision making. FS is most useful in those cases that
      are diagnosed as suspicious for papillary carcinoma by FNA.

PMID- 20044649
TI  - Serum (1->3)-{beta}-D-Glucan assay for the diagnosis of Pneumocystis jiroveci
      pneumonia.

PMID- 20044650
TI  - National dissemination of effective parenting programmes to improve child
      outcomes.
AB  - Although living standards have increased in the past 40 years, children's
      behaviour problems have become worse. Good parenting can help by maximising
      children's potential and promoting resilience. Effective programmes are available
      that improve parenting, but unfortunately ineffective approaches are still used
      widely. A new National Academy for Parenting Practitioners has been set up in
      England, which offers free training in evidence-based interventions and conducts
      research to increase their effectiveness.

PMID- 20044651
TI  - Pharmacotherapy for borderline personality disorder: Cochrane systematic review
      of randomised trials.
AB  - BACKGROUND: Many patients with borderline personality disorder receive
      pharmacological treatment, but there is uncertainty about the usefulness of such
      therapies. AIMS: To evaluate the evidence of effectiveness of pharmacotherapy in
      treating different facets of the psychopathology of borderline personality
      disorder. METHOD: A Cochrane Collaboration systematic review and meta-analysis of
      randomised comparisons of drug v. placebo, drug v. drug, or single drug v.
      combined drug treatment in adult patients with borderline personality disorder
      was conducted. Primary outcomes were overall disorder severity as well as
      specific core symptoms. Secondary outcomes comprised associated psychiatric
      pathology and drug tolerability. RESULTS: Twenty-seven trials were included in
      which first- and second-generation antipsychotics, mood stabilisers,
      antidepressants and omega-3 fatty acids were tested. Most beneficial effects were
      found for the mood stabilisers topiramate, lamotrigine and valproate semisodium,
      and the second-generation antipsychotics aripiprazole and olanzapine. However,
      the robustness of findings is low, since they are based mostly on single, small
      studies. Selective serotonin reuptake inhibitors so far lack high-level evidence
      of effectiveness. CONCLUSIONS: The current evidence from randomised controlled
      trials suggests that drug treatment, especially with mood stabilisers and second
      generation antipsychotics, may be effective for treating a number of core
      symptoms and associated psychopathology, but the evidence does not currently
      support effectiveness for overall severity of borderline personality disorder.
      Pharmacotherapy should therefore be targeted at specific symptoms.

PMID- 20044653
TI  - Comparison of risk factors for the onset and maintenance of depression.
AB  - BACKGROUND: Factors associated with depression are usually identified from cross
      sectional studies. AIMS: We explore the relative roles of onset and recovery in
      determining these associations. METHOD: Hazard ratios for onset and recovery were
      estimated for 39 risk factors from a cohort study of 10,045 general practice
      attendees whose depression status was assessed at baseline, 6 and 12 months.
      RESULTS: Risk factors have a stronger relative effect on the rate of onset than
      recovery. The strongest risk factors for both onset and maintenance of depression
      tend to be time-dependent. With the exception of female gender the strength of a
      risk factor's effect on onset is highly predictive of its impact on recovery.
      CONCLUSIONS: Preventive measures will achieve a greater reduction in the
      prevalence of depression than measures designed to eliminate risk factors post
      onset. The strength of time-dependent risk factors suggests that it is more
      productive to focus on proximal rather than distal factors.

PMID- 20044654
TI  - Risk of psychological distress following severe obstetric complications in Benin:
      the role of economics, physical health and spousal abuse.
AB  - BACKGROUND: Little is known about the impact of life-threatening obstetric
      complications ('near miss') on women's mental health in low- and middle-income
      countries. AIMS: To examine the relationships between near miss and postpartum
      psychological distress in the Republic of Benin. METHOD: One-year prospective
      cohort using epidemiological and ethnographic techniques in a population of women
      delivering at health facilities. RESULTS: In total 694 women contributed to the
      study. Except when associated with perinatal death, near-miss events were not
      associated with greater risk of psychological distress in the 12 months
      postpartum compared with uncomplicated childbirth. Much of the direct effect of
      near miss with perinatal death on increased risk of psychological distress was
      shown to be mediated through wider consequences of traumatic childbirth.
      CONCLUSIONS: A live baby protects near-miss women from increased vulnerability by
      giving a positive element in their lives that helps them cope and reduces their
      risk of psychological distress. Near-miss women with perinatal death should be
      targeted early postpartum to prevent or treat the development of depressive
      symptoms.

PMID- 20044655
TI  - Risk factors for suicide in rural south India.
AB  - BACKGROUND: The relative contributions of psychosocial stress and psychiatric
      morbidity to suicide are a subject of debate. AIMS: To determine major risk
      factors for suicide in rural south India. METHOD: We used a matched case-control
      design and psychological autopsy to assess 100 consecutive suicides and 100
      living controls matched for age, gender and neighbourhood. RESULTS: Thirty-seven
      (37%) of those who died by suicide had a DSM-III-R psychiatric diagnosis. Alcohol
      dependence (16%) and adjustment disorders (15%) were the most common categories.
      The prevalence rates for schizophrenia, major depressive episode and dysthymia
      were 2% each. Ongoing stress and chronic pain heightened the risk of suicide.
      Living alone and a break in a steady relationship within the past year were also
      significantly associated with suicide. CONCLUSIONS: Psychosocial stress and
      social isolation, rather than psychiatric morbidity, are risk factors for suicide
      in rural south India.

PMID- 20044656
TI  - Non-fatal repetition of self-harm: population-based prospective cohort study in
      Taiwan.
AB  - BACKGROUND: Repeated self-harm is relatively common and is linked with an
      elevated risk of eventual suicide. There has been no study of this involving a
      large sample from the Far East. AIMS: To estimate the risk over the medium term
      of non-fatal repetition of self-harm and identify predictive factors in those
      carrying out self-harm. METHOD: A total of 970 individuals who had self-harmed
      were recruited from a community-based suicide behaviour register system in
      Nantou, Taiwan from July 2000 to February 2003. Information regarding demography
      and suicide methods was collected. Individuals were followed-up until December
      2005 to examine the risk of repeated self-harm and independent predictive
      factors. RESULTS: Ninety cohort members had repeated self-harm during the follow
      up period (accounting for 131 repeated self-harm episodes in all). The cumulative
      risks were 5.7% for the first year, 7.8% for the second year and 9.5% for the
      fourth year. The risk was highest within the first year after the self-harm
      event. Independent risk factors included female gender and self-cutting as well
      as self-poisoning with drugs. Effect of younger age was mediated through the
      choice of methods. CONCLUSIONS: Individuals with self-harm have a high risk of
      repetition, especially within the first year. Suicide prevention strategies need
      to focus on intervening with this population to reduce their repetition.

PMID- 20044657
TI  - Risk of developing dementia in people with diabetes and mild cognitive
      impairment.
AB  - BACKGROUND: Diabetes mellitus is associated with cognitive dysfunction, but it is
      not clear whether the disorder increases the risk of conversion from mild
      cognitive impairment to dementia. AIMS: To determine the association between
      diabetes mellitus and dementia conversion in people with mild cognitive
      impairment (Peterson's criteria) in a prospective community-based study. METHOD:
      People over 65 years old were approached through primary care practices in south
      London, UK, and those with mild cognitive impairment (n = 103) were followed up
      for 4 years. Presence of diabetes was established from self-report and
      information from general practitioners. RESULTS: Nineteen participants progressed
      to dementia, with the predominant diagnosis being probable or possible
      Alzheimer's disease (in 84%). Only diabetes mellitus was associated with
      progression to dementia (hazard ratio 2.9, 95% CI 1.1-7.3) after adjustment for
      sociodemographic factors, APOE4, premorbid IQ and other health conditions.
      CONCLUSIONS: Diabetes mellitus increases not only the risks of dementia and mild
      cognitive impairment but also the risk of progression from such impairment to
      dementia.

PMID- 20044659
TI  - Prevalence and correlates of auditory vocal hallucinations in middle childhood.
AB  - BACKGROUND: Hearing voices occurs in middle childhood, but little is known about
      prevalence, aetiology and immediate consequences. AIMS: To investigate
      prevalence, developmental risk factors and behavioural correlates of auditory
      vocal hallucinations in 7- and 8-year-olds. METHOD: Auditory vocal hallucinations
      were assessed with the Auditory Vocal Hallucination Rating Scale in 3870
      children. Prospectively recorded data on pre- and perinatal complications, early
      development and current problem behaviour were analysed in children with auditory
      vocal hallucinations and matched controls. RESULTS: The 1-year prevalence of
      auditory vocal hallucinations was 9%, with substantial suffering and problem
      behaviour reported in 15% of those affected. Prevalence was higher in rural areas
      but auditory vocal hallucinations were more severe and had greater functional
      impact in the urban environment. There was little evidence for associations with
      developmental variables. CONCLUSIONS: Auditory vocal hallucinations in 7- and 8
      year-olds are prevalent but mostly of limited functional impact. Nevertheless,
      there may be continuity with more severe psychotic outcomes given the serious
      suffering in a subgroup of children and there is evidence for a poorer prognosis
      in an urban environment.

PMID- 20044660
TI  - Brain serotonin-2 receptors in acute mania.
AB  - BACKGROUND: Although 5-hydroxytryptamine (5-HT) has been implicated in mania, the
      precise alterations in the 5-HT system remain elusive. AIMS: To assess brain 5
      HT2 receptors in drug-free individuals experiencing a manic episode in comparison
      with healthy volunteers using positron emission tomography (PET). METHOD:
      Participants (n = 10) with DSM-IV bipolar I disorder-manic episode and healthy
      controls (n = 10) underwent [18F]-setoperone scans. The differences in 5-HT2
      receptor binding potential between the two groups were determined using
      statistical parametric mapping (SPM) analysis. RESULTS: Age was a significant
      correlate with 5-HT2 receptor binding potential with a similar magnitude of
      correlation in both groups. The SPM analysis with age as a covariate showed that
      the individuals with current mania had significantly lower 5-HT2 receptor binding
      potential in frontal, temporal, parietal and occipital cortical regions, with
      changes more prominent in the right cortical regions compared with controls.
      CONCLUSIONS: This study suggests that brain 5-HT2 receptors are decreased in
      people with acute mania.

PMID- 20044661
TI  - White matter microstructural abnormalities in euthymic bipolar disorder.
AB  - BACKGROUND: Abnormal diffusion parameters are reported in specific brain regions
      and white matter tracts in bipolar disorder. AIMS: To investigate whether these
      abnormalities are generalised, and thus evident in large regions of white matter.
      METHOD: Diffusion parameters were measured at several regions in the corpus
      callosum and in deep/periventricular white matter in 28 currently euthymic
      patients with bipolar disorder and controls. White matter hyperintensity loads
      were assessed. RESULTS: Comparing the whole data-sets using the sign test, in the
      group with bipolar disorder, mean diffusivity was greater at all 15 sites
      (P<0.001) and fractional anisotropy was reduced at 13 (P<0.01). The effect of
      diagnosis was significant for callosal mean diffusivity and fractional anisotropy
      and for deep/periventricular mean diffusivity (MANCOVA). Comparing individual
      regions (Mann-Whitney U-test), prefrontal and periventricular mean diffusivity
      were significantly increased; callosal and occipital fractional anisotropy were
      significantly reduced. Former substance use and lithium were possible confounding
      factors. Periventricular white matter hyperintensities were associated with
      significantly increased periventricular mean diffusivity in individuals with
      bipolar disorder. CONCLUSIONS: Generalised white matter microstructural
      abnormalities may exist in bipolar disorder, possibly exacerbated by past
      substance use and ameliorated by lithium.

PMID- 20044662
TI  - Enhanced relapse prevention for bipolar disorder by community mental health
      teams: cluster feasibility randomised trial.
AB  - BACKGROUND: Relapse prevention for bipolar disorder increases time to relapse but
      is not available in routine practice. AIMS: To determine the feasibility and
      effectiveness of training community mental health teams (CMHTs) to deliver
      enhanced relapse prevention. METHOD: In a cluster randomised controlled trial,
      CMHT workers were allocated to receive 12 h training in enhanced relapse
      prevention to offer to people with bipolar disorder or to continue giving
      treatment as usual. The primary outcome was time to relapse and the secondary
      outcome was functioning. RESULTS: Twenty-three CMHTs and 96 service users took
      part. Compared with treatment as usual, enhanced relapse prevention increased
      median time to the next bipolar episode by 8.5 weeks (hazard ratio 0.79, 95% CI
      0.45-1.38). Social and occupational functioning improved with the intervention
      (regression coefficient 0.68, 95% CI 0.05-1.32). The clustering effect was
      negligible but imprecise (intracluster correlation coefficient 0.0001, 95% CI
      0.0000-0.5142). CONCLUSIONS: Training care coordinators to offer enhanced relapse
      prevention for bipolar disorder may be a feasible effective treatment. Large
      scale cluster trials are needed.

PMID- 20044664
TI  - Validity of a short clinical interview for psychiatric diagnosis: the mini-SCAN.
AB  - BACKGROUND: To promote clinical application of the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN) system a shorter version (the mini-SCAN) was
      devised. Its psychometric properties were unknown. AIMS: To establish the
      validity and practical properties of the mini-SCAN. METHOD: One hundred and six
      participants were interviewed twice, once with the SCAN and once with the mini
      SCAN. The level of agreement was established for the categories: no disorder,
      affective disorders, anxiety disorders, non-affective psychotic disorders,
      affective psychotic disorders. RESULTS: The mini-SCAN is a valid instrument. Most
      kappa values were around 0.90. Only for the class of affective psychotic
      disorders was the agreement moderate. Mean duration of the mini-SCAN interviews
      was 25 min shorter than the SCAN interviews. Participants and interviewers were
      generally satisfied with the interview format and questions. CONCLUSIONS: The
      mini-SCAN can be used as a diagnostic instrument for clinical purposes and for
      clinical studies when the present episode is the focus of attention.

PMID- 20044665
TI  - TENTS guidelines: development of post-disaster psychosocial care guidelines
      through a Delphi process.
AB  - BACKGROUND: How best to plan and provide psychosocial care following disasters
      remains keenly debated. AIMS: To develop evidence-informed post-disaster
      psychosocial management guidelines. METHOD: A three-round web-based Delphi
      process was conducted. One hundred and six experts rated the importance of
      statements generated from existing evidence using a one to nine scale.
      Participants reassessed their original scores in the light of others' responses
      in the subsequent rounds. RESULTS: A total of 80 (72%) of 111 statements achieved
      consensus for inclusion. The statement 'all responses should provide access to
      pharmacological assessment and management' did not achieve consensus. The final
      guidelines recommend that every area has a multi-agency psychosocial care
      planning group, that responses provide general support, access to social,
      physical and psychological support and that specific mental health interventions
      are only provided if indicated by a comprehensive assessment. Trauma-focused
      cognitive-behavioural therapy (CBT) is recommended for acute stress disorder or
      acute post-traumatic stress disorder, with other treatments with an evidence base
      for chronic post-traumatic stress disorder being made available if trauma-focused
      CBT is not tolerated. CONCLUSIONS: The Delphi process allowed a consensus to be
      achieved in an area where there are limitations to the current evidence.

PMID- 20044667
TI  - Ethnicity and coercion among involuntarily detained psychiatric in-patients.
AB  - We assessed whether adult Black and minority ethnic (BME) patients detained for
      involuntary psychiatric treatment experienced more coercion than similar White
      patients. We found no evidence of this from patient interviews or from hospital
      records. The area (mental health trust) where people were treated was strongly
      associated with both the experience of coercion and the recording of a coercive
      measure in their records. Regarding charges of institutional racism in
      psychiatry, this study highlights the importance of investigating the role of
      area characteristics when assessing the relationship between ethnicity and
      patient management.

PMID- 20044668
TI  - Assertive community treatment teams.

PMID- 20044669
TI  - Naltrexone implants.

PMID- 20044670
TI  - Assertive community treatment teams.

PMID- 20044671
TI  - What is the role of lateral retinacular release?
AB  - We have reviewed the literature to establish the role of lateral retinacular
      release in the management of disorders of the extensor apparatus of the knee. The
      scientific evidence for intervention is explored and reports on outcome are
      discussed.

PMID- 20044672
TI  - A new musculoskeletal curriculum: has it made a difference?
AB  - This study assessed whether undergraduate performance improved following the
      introduction in 2006 of a musculoskeletal teaching programme lasting for seven
      weeks. Different methods were used to deliver knowledge and skills in trauma and
      orthopaedic surgery, rheumatology and allied specialties. The programme combined
      four main elements: traditional firm-based teaching, weekly plenary sessions, a
      task-based workbook and additional specialist clinics. The block of 139 students
      who attended in its first year were assessed using a multiple choice question
      examination just before their final examinations in 2008. They showed a 6%
      improvement in performance over a control group of 130 students assessed in 2005
      before the programme had commenced. There was no difference in performance
      between the students assessed in 2005 and a second group of 46 students from 2008
      who did not attend the new teaching programme. Performance was improved by
      providing more focused musculoskeletal training using available resources, as
      well as increasing the length of the programme.

PMID- 20044673
TI  - Metal ion release from bearing wear and corrosion with 28 mm and large-diameter
      metal-on-metal bearing articulations: a follow-up study.
AB  - We have updated our previous randomised controlled trial comparing release of
      chromium (Cr) and cobalt (Co) ions and included levels of titanium (Ti) ions. We
      have compared the findings from 28 mm metal-on-metal total hip replacement,
      performed using titanium CLS/Spotorno femoral components and titanium AlloFit
      acetabular components with Metasul bearings, with Durom hip resurfacing using a
      Metasul articulation or bearing and a titanium plasma-sprayed coating for
      fixation of the acetabular component. Although significantly higher blood ion
      levels of Cr and Co were observed at three months in the resurfaced group than in
      total hip replacement, no significant difference was found at two years post
      operatively for Cr, 1.58 microg/L and 1.62 microg/L respectively (p = 0.819) and
      for Co, 0.67 microg/L and 0.94 microg/L respectively (p = 0.207). A steady state
      was reached at one year in the resurfaced group and after three months in the
      total hip replacement group. Interestingly, Ti, which is not part of the bearing
      surfaces with its release resulting from metal corrosion, had significantly
      elevated ion levels after implantation in both groups. The hip resurfacing group
      had significantly higher Ti levels than the total hip replacement group for all
      periods of follow-up. At two years the mean blood levels of Ti ions were 1.87
      microg/L in hip resurfacing and and 1.30 microg/L in total hip replacement (p =
      0.001). The study confirms even with different bearing diameters and clearances,
      hip replacement and 28 mm metal-on-metal total hip replacement produced similar
      Cr and Co metal ion levels in this randomised controlled trial study design, but
      apart from wear on bearing surfaces, passive corrosion of exposed metallic
      surfaces is a factor which influences ion concentrations. Ti plasma spray coating
      the acetabular components for hip resurfacing produces significantly higher
      release of Ti than Ti grit-blasted surfaces in total hip replacement.

PMID- 20044674
TI  - Ten-year results of a double-heat-treated metal-on-metal hip resurfacing.
AB  - Second-generation metal-on-metal bearings were introduced as a response to the
      considerable incidence of wear-induced failures associated with conventional
      replacements, especially in young patients. We present the results at ten years
      of a consecutive series of patients treated using a metal-on-metal hip
      resurfacing. A distinct feature of the bearings used in our series was that they
      had been subjected to double-heat treatments during the post-casting phase of
      their manufacture. In the past these bearings had not been subjected to thermal
      treatments, making this a unique metal-on-metal bearing which had not been used
      before in clinical practice. We report the outcome of 184 consecutive hips (160
      patients) treated using a hybrid-fixed metal-on-metal hip resurfacing during
      1996. Patients were invited for a clinicoradiological follow-up at a minimum of
      ten years. The Oxford hip score and anteroposterior and lateral radiographs were
      obtained. The mean age at operation was 54 years (21 to 75). A series of 107
      consecutive hips (99 patients) who received the same prosthesis, but subjected to
      a single thermal treatment after being cast, between March 1994 and December
      1995, were used as a control group for comparison. In the 1994 to 1995 group
      seven patients (seven hips) died from unrelated causes and there were four
      revisions (4%) for osteolysis and aseptic loosening. In the 1996 group nine
      patients died at a mean of 6.9 years after operation because of unrelated causes.
      There were 30 revisions (16%) at a mean of 7.3 years (1.2 to 10.9), one for
      infection at 1.2 years and 29 for osteolysis and aseptic loosening. Furthermore,
      in the latter group there were radiological signs of failure in 27 (24%) of the
      111 surviving hips. The magnitude of the problem of osteolysis and aseptic
      loosening in the 1996 cohort did not become obvious until five years after the
      operation. Our results indicate that double-heat treatments of metal-on-metal
      bearings can lead to an increased incidence of wear-induced osteolysis.

PMID- 20044675
TI  - Articular surface replacement of the hip: a prospective single-surgeon series.
AB  - We present the early clinical and radiological results of Articular Surface
      Replacement (ASR) resurfacings in 214 hips (192 patients) with a mean follow-up
      of 43 months (30 to 57). The mean age of the patients was 56 years (28 to 74) and
      85 hips (40%) were in 78 women. The mean Harris hip score improved from 52 (11 to
      81) to 95 (27 to 100) at two years and the mean University of California, Los
      Angeles activity score from 3.9 (1 to 10) to 7.4 (2 to 10) in the same period.
      Narrowing of the neck (to a maximum of 9%) was noted in 124 of 209 hips (60%).
      There were 12 revisions (5.6%) involving four (1.9%) early fractures of the
      femoral neck and two (0.9%) episodes of collapse of the femoral head secondary to
      avascular necrosis. Six patients (2.8%) had failure related to metal wear debris.
      The overall survival for our series was 93% (95% confidence interval 80 to 98)
      and 89% (95% confidence interval 82 to 96) for hips with acetabular components
      smaller than 56 mm in diameter. The ASR implant has a lower diametrical clearance
      and a subhemispherical acetabular component when compared with other more
      frequently implanted metal-on-metal hip resurfacings. These changes may
      contribute to the higher failure rate than in other series, compared with other
      designs. Given our poor results with the small components we are no longer
      implanting the smaller size.

PMID- 20044676
TI  - Early failure of metal-on-metal bearings in hip resurfacing and large-diameter
      total hip replacement: A consequence of excess wear.
AB  - Early failure associated with adverse reactions to metal debris is an emerging
      problem after hip resurfacing but the exact mechanism is unclear. We analysed our
      entire series of 660 metal-on-metal resurfacings (Articular Surface Replacement
      (ASR) and Birmingham Hip Resurfacing (BHR)) and large-bearing ASR total hip
      replacements, to establish associations with metal debris-related failures.
      Clinical and radiological outcomes, metal ion levels, explant studies and
      lymphocyte transformation tests were performed. A total of 17 patients (3.4%)
      were identified (all ASR bearings) with adverse reactions to metal debris, for
      which revision was required. This group had significantly smaller components,
      significantly higher acetabular component anteversion, and significantly higher
      whole concentrations of blood and joint chromium and cobalt ions than
      asymptomatic patients did (all p < 0.001). Post-revision lymphocyte
      transformation tests on this group showed no reactivity to chromium or cobalt
      ions. Explants from these revisions had greater surface wear than retrievals for
      uncomplicated fractures. The absence of adverse reactions to metal debris in
      patients with well-positioned implants usually implies high component wear.
      Surgeons must consider implant design, expected component size and acetabular
      component positioning in order to reduce early failures when performing large
      bearing metal-on-metal hip resurfacing and replacement.

PMID- 20044677
TI  - Is the frog lateral plain radiograph a reliable predictor of the alpha angle in
      femoroacetabular impingement?
AB  - The radiological evaluation of the anterolateral femoral head is an essential
      tool for the assessment of the cam type of femoroacetabular impingement. CT, MRI
      and frog lateral plain radiographs have all been suggested as imaging options for
      this type of lesion. The alpha angle is accepted as a reliable indicator of the
      cam type of impingement and may also be used as an assessment for the successful
      operative correction of the cam lesion. We studied the alpha angles of 32
      consecutive patients with femoroacetabular impingement. The angle measured on
      frog lateral radiographs using templating tools was compared with that measured
      on CT scans in order to assess the reliability of the frog lateral view in
      analysing the alpha angle in cam impingement. A high interobserver reliability
      was noted for the assessment of the alpha angle on the frog lateral view with an
      intraclass correlation coefficient of 0.83. The mean alpha angle measured on the
      frog lateral view was 58.71 degrees (32 degrees to 83.3 degrees ) and that by CT
      was 65.11 degrees (30 degrees to 102 degrees ). A poor intraclass correlation
      coefficient (0.08) was noted between the measurements using the two systems. The
      frog lateral plain radiograph is not reliable for measuring the alpha angle.
      Various factors may be responsible for this such as the projection of the
      radiograph, the positioning of the patient and the quality of the image. CT may
      be necessary for accurate measurement of the alpha angle.

PMID- 20044678
TI  - Measurement of joint effusion and haematoma formation by ultrasound in assessing
      the effectiveness of drains after total knee replacement: A prospective
      randomised study.
AB  - We prospectively randomised 78 patients into two groups, 'drains' or 'no drains'
      to assess the effectiveness of suction drains in reducing haematoma and effusion
      in the joint and its effect on wound healing after total knee replacement.
      Ultrasound was used to measure the formation of haematoma and effusion on the
      fourth post-operative day. This was a semi-quantitative assessment of volume
      estimation. There was no difference in the mean effusion between the groups (5.91
      mm in the drain group versus 6.08 mm in the no-drain, p = 0.82). The mean amount
      of haematoma in the no-drain group was greater (11.07 mm versus 8.41 mm, p =
      0.03). However, this was not clinically significant judged by the lack of
      difference in the mean reduction in the post-operative haemoglobin between the
      groups (drain group 3.4 g/dl; no-drain group 3.0 g/dl, p = 0.38). There were no
      cases of wound infection or problems with wound healing at six weeks in any
      patient. Our findings indicate that drains do not reduce joint effusion but do
      reduce haematoma formation. They have no effect on wound healing.

PMID- 20044679
TI  - The Avon patellofemoral joint replacement: Five-year results from an independent
      centre.
AB  - Between May 1998 and May 2007 we carried out 50 Avon patellofemoral joint
      replacements in 32 patients with isolated patellofemoral osteoarthritis. There
      were no revisions in the first five years, giving a cumulative survival of 100%
      for those with a minimum follow-up of five years. The mean follow-up was 5.3
      years (2.1 to 10.2). The median Oxford knee score was 30.5 (interquartile range
      22.25 to 42.25). In patients with bilateral replacements the median Euroqol
      General health score was 50 which was significantly lower than that of 75 in
      those with a unilateral replacement (p = 0.047). The main complication was
      progression of disease, which was identified radiologically in 11 knees (22%).
      This highlights the need for accurate selection of patients. Our findings suggest
      that the Avon prosthesis survives well and gives a satisfactory functional
      outcome in the medium term.

PMID- 20044680
TI  - Total ankle replacement by the Ankle Evolution System: medium-term outcome.
AB  - We present the outcomes in 38 consecutive patients who had total ankle
      replacement using the Ankle Evolution System with a minimum follow-up of four
      years. Pain and function were assessed using the American Orthopaedic Foot and
      Ankle Society (AOFAS) score and regular standardised anteroposterior and lateral
      weight-bearing radiographs were obtained. Patient satisfaction and complications
      were recorded and the survival of the implants was demonstrated by the Kaplan
      Meier method. The mean follow-up was for 57.8 months (48 to 80). The cumulative
      survival rate at six years was 94.7% (95% confidence interval 80.3 to 98.7). The
      mean total AOFAS score was 88.1 (53 to 100). The mean score for pain was 35.8 (20
      to 40). Ten patients presented with edge-loading of whom nine had corrective
      surgery. Two ankles were revised, one to an arthrodesis and the other to replace
      the tibial component. Nine patients showed radiological evidence of osteolysis.
      They had minimal non-progressive symptoms and further surgery was not undertaken.
      Nevertheless, the concerns about osteolysis led to the implant being withdrawn by
      the manufacturer. The medium-term results of the ankle evolution system ankle
      replacement are satisfactory with high patient satisfaction, but the rate of
      osteolysis is of some concern. The long-term benefit of this procedure has yet to
      be determined.

PMID- 20044681
TI  - Treatment of malunited fractures of the ankle: A long-term follow-up of
      reconstructive surgery.
AB  - In this retrospective study, using the prospectively collected database of the AO
      Documentation Centre, we analysed the outcome of 57 malunited fractures of the
      ankle treated by reconstructive osteotomy. In all cases the position of the
      malunited fibula had been corrected, in several cases it was combined with other
      osteotomies and the fixation of any non-united fragments. Patients were seen on a
      regular basis, with a minimum follow-up of ten years. The aim of the study was to
      establish whether reconstruction improves ankle function and prevents the
      progression of arthritic changes. Good or excellent results were obtained in 85%
      (41) of patients indicating that reconstructive surgery is effective in most and
      that the beneficial effects can last for up to 27 years after the procedure.
      Minor post-traumatic arthritis is not a contraindication but rather an indication
      for reconstructive surgery. We also found that prolonged time to reconstruction
      is associated negatively with outcome.

PMID- 20044682
TI  - Treatment of locked chronic posterior dislocation of the shoulder by
      reconstruction of the defect in the humeral head with an allograft.
AB  - The treatment of a chronic posterior dislocation of the shoulder is often
      determined by the size of the associated impression fracture of the humeral head.
      Our hypothesis was that patients with a chronic unreduced posterior dislocation
      of the shoulder and a defect in the humeral head involving between 25% to 50% of
      the articular surface, would do better if reconstructed with an allograft from
      the femoral head rather than treated by a non-anatomical reconstruction. We
      reviewed ten men and three women with a mean age of 42 years (36 to 51) at a mean
      follow-up of 54 months (41 to 64) who had this procedure. At follow-up, nine had
      no pain or restriction of activities of daily living. Their mean Constant-Murley
      shoulder score was 86.8 (43 to 98). No patient had symptoms of instability of the
      shoulder. Reconstruction of the defect in the humeral head with an allograft
      provides good pain relief, stability and function for patients with a locked,
      chronic posterior dislocation where the defect involves between 25% and 50% of
      the circumference of the articular surface.

PMID- 20044683
TI  - A double-blind randomised controlled study comparing subacromial injection of
      tenoxicam or methylprednisolone in patients with subacromial impingement.
AB  - We have carried out a prospective double-blind randomised controlled trial to
      compare the efficacy of a single subacromial injection of the non-steroidal anti
      inflammatory drug, tenoxicam, with a single injection of methylprednisolone in
      patients with subacromial impingement. A total of 58 patients were randomly
      allocated into two groups. Group A received 40 mg of methylprednisolone and group
      B 20 mg of tenoxicam as a subacromial injection along with lignocaine. The
      Constant-Murley shoulder score was used as the primary outcome measure and the
      Disability of Arm, Shoulder and Hand (DASH) and the Oxford Shoulder Score (OSS)
      as secondary measures. Six weeks after injection the improvement in the Constant
      Murley score was significantly greater in the methylprednisolone group (p =
      0.003) than in the tenoxicam group. The improvement in the DASH score was greater
      in the steroid group and the difference was statistically significant and
      consistent two (p < 0.01), four (p < 0.01) and six weeks (p < 0.020) after the
      injection. The improvement in the OSS was consistently greater in the steroid
      group than in the tenoxicam group. Although the difference was statistically
      significant at two (p < 0.001) and four (p = 0.003) weeks after the injection, it
      was not at six weeks (p = 0.055). Subacromial injection of tenoxicam does not
      offer an equivalent outcome to subacromial injection of corticosteroid at six
      weeks. Corticosteroid is significantly better than tenoxicam for improving
      shoulder function in tendonitis of the rotator cuff after six weeks.

PMID- 20044684
TI  - Comparison between surgery and physiotherapy in the treatment of small and medium
      sized tears of the rotator cuff: A randomised controlled study of 103 patients
      with one-year follow-up.
AB  - In order to compare the outcome from surgical repair and physiotherapy, 103
      patients with symptomatic small and medium-sized tears of the rotator cuff were
      randomly allocated to one of the two approaches. The primary outcome measure was
      the Constant score, and secondary outcome measures included the self-report
      section of the American Shoulder and Elbow Surgeons score, the Short Form 36
      Health Survey and subscores for shoulder movement, pain, strength and patient
      satisfaction. Scores were taken at baseline and after six and 12 months by a
      blinded assessor. Nine patients (18%) with insufficient benefit from
      physiotherapy after at least 15 treatment sessions underwent secondary surgical
      treatment. Analysis of between-group differences showed better results for the
      surgery group on the Constant scale (difference 13.0 points, p - 0.002), on the
      American Shoulder and Elbow surgeons scale (difference 16.1 points, p < 0.0005),
      for pain-free abduction (difference 28.8 degrees , p = 0.003) and for reduction
      in pain (difference on a visual analogue scale -1.7 cm, p < 0.0005).

PMID- 20044685
TI  - Management of severe extra-articular contracture of the elbow by open arthrolysis
      and a monolateral hinged external fixator.
AB  - Arthrolysis and dynamic splinting have been used in the treatment of elbow
      contractures, but there is no standardised protocol for treatment of severe
      contractures with an arc of flexion < 30 degrees . We present our results of
      radical arthrolysis with twin incisions with the use of a monolateral hinged
      fixator to treat very severe extra-articular contracture of the elbow. This
      retrospective study included 26 patients (15 males and 11 females) with a mean
      age of 30 years (12 to 60). The mean duration of stiffness was 9.1 months (5.4 to
      18) with mean follow-up of 5.2 years (3.5 to 9.4). The mean pre-operative arc of
      movement was 15.6 degrees (0 degrees to 30 degrees ), with mean pre-operative
      flexion of 64.1 degrees (30 degrees to 120 degrees ) and mean pre-operative
      extension of 52.1 degrees (10 degrees to 90 degrees ). Post-operatively the mean
      arc improved to 102.4 degrees (60 degrees to 135 degrees ), the mean flexion
      improved to 119.1 degrees (90 degrees to 140 degrees ) and mean extension
      improved to 16.8 degrees (0 degrees to 30 degrees ) (p < 0.001). The Mayo elbow
      score improved from a mean of 45 (30 to 65) to 89 (75 to 100) points, and 13 had
      excellent, nine had good, three had fair and one had a poor result. We had one
      case of severe instability and one wound dehiscence which responded well to
      treatment. One case had deep infection with poor results which responded well to
      treatment. Our findings indicate that this method is very effective in the
      treatment of severe elbow contracture; however, a randomised controlled study is
      necessary for further evaluation.

PMID- 20044686
TI  - Management of fractures of the pedicle after instrumentation with transpedicular
      screws: A report of three patients.
AB  - Fracture of a pedicle is a rare complication of spinal instrumentation using
      pedicular screws, but it can lead to instability and pain and may necessitate
      extension of the fusion. Osteosynthesis of the fractured pedicle by cerclage-wire
      fixation and augmentation of the screw fixation by vertebroplasty or temporary
      elongation of the fixation, allows stabilisation without sacrifice of the
      adjacent healthy segment. We describe three patients who developed a fracture of
      the pedicle in the most caudal instrumented vertebra early after lumbar spinal
      fusion. During revision surgery the pedicles were reduced and secured by a soft
      cerclage wire bilaterally. Fusion was obtained at the site of the primary
      instrumentation and healing of the pedicles was achieved. Cerclage wiring of the
      fractured pedicle seems to be safe and avoids permanent extension of the fusion
      without the sacrifice of an otherwise healthy segment.

PMID- 20044687
TI  - Posterior dislocation of the sternoclavicular joint and epiphyseal disruption of
      the medial clavicle with posterior displacement in sports participants.
AB  - We retrospectively analysed the clinical results of 30 patients with injuries of
      the sternoclavicular joint at a minimum of 12 months' follow-up. A closed
      reduction was attempted in 14 cases. It was successful in only five of ten
      dislocations, and failed in all four epiphyseal disruptions. A total of 25
      patients underwent surgical reduction, in 18 cases in conjunction with a
      stabilisation procedure. At a mean follow-up of 60 months, four patients were
      lost to follow-up. The functional results in the remainder were satisfactory, and
      18 patients were able to resume their usual sports activity at the same level.
      There was no statistically significant difference between epiphyseal disruption
      and sternoclavicular dislocation (p > 0.05), but the functional scores (Simple
      Shoulder Test, Disability of Arm, Shoulder, Hand, and Constant scores) were
      better when an associated stabilisation procedure had been performed rather than
      reduction alone (p = 0.05, p = 0.04 and p = 0.07, respectively). We recommend
      meticulous pre-operative clinical assessment with CT scans. In sternoclavicular
      dislocation managed within the first 48 hours and with no sign of mediastinal
      complication, a closed reduction can be attempted, although this was unsuccessful
      in half of our cases. A control CT scan is mandatory. In all other cases, and
      particularly if epiphyseal disruption is suspected, we recommend open reduction
      with a stabilisation procedure by costaclavicular cerclage or tenodesis. The use
      of a Kirschner wire should be avoided.

PMID- 20044688
TI  - Operative treatment of patients with pertrochanteric femoral fractures outside
      working hours is not associated with a higher incidence of complications or
      higher mortality.
AB  - This retrospective cohort study was conducted to investigate whether operative
      treatment of patients with a pertrochanteric femoral fracture outside working
      hours is associated with an increased risk of complications and higher mortality.
      During the study period 165 patients were operated on outside working hours and
      123 were operated on during working hours (08.00 to 17.00). There was no
      difference in the rate of early complications (outside working hours 33% versus
      working hours 33%, p = 0.91) or total complications during follow-up (outside
      working hours 40% versus working hours 41%, p = 0.91). Both in-hospital mortality
      (outside working hours 12% versus working hours 11%, p = 0.97) and mortality
      after one year (outside working hours 29% versus working hours 27%, p = 0.67)
      were comparable. Adjustment for possible confounders by multivariate logistic
      regression analysis revealed no increased risk of complications when patients
      were operated on outside working hours. On the basis of these data, there is no
      medical reason to postpone operative reduction and fixation in patients with a
      proximal femoral fracture until working hours.

PMID- 20044689
TI  - Cemented versus uncemented hemiarthroplasty for intracapsular hip fractures: A
      randomised controlled trial in 400 patients.
AB  - We undertook a prospective randomised controlled trial involving 400 patients
      with a displaced intracapsular fracture of the hip to determine whether there was
      any difference in outcome between treatment with a cemented Thompson
      hemiarthroplasty and an uncemented Austin-Moore prosthesis. The surviving
      patients were followed up for between two and five years by a nurse blinded to
      the type of prosthesis used. The mean age of the patients was 83 years (61 to
      104) and 308 (77%) were women. The degree of residual pain was less in those
      treated with a cemented prosthesis (p < 0.0001) three months after surgery.
      Regaining mobility was better in those treated with a cemented implant (p =
      0.005) at six months after operation. No statistically significant difference was
      found between the two groups with regard to mortality, implant-related
      complications, re-operations or post-operative medical complications. The use of
      a cemented Thompson hemiarthroplasty resulted in less pain and less deterioration
      in mobility than an uncemented Austin-Moore prosthesis with no increase in
      complications.

PMID- 20044690
TI  - The impact of national guidelines for the prophylaxis of venous thromboembolism
      on the complications of arthroplasty of the lower limb.
AB  - The National Institute for Clinical Excellence (NICE) produces recommendations on
      appropriate treatment within the National Health Service (NHS) in England and
      Wales. The NICE guidelines on prophylaxis for venous thromboembolism in
      orthopaedic surgery recommend that all patients be offered a low molecular weight
      heparin (LMWH). The linked hospital episode statistics of 219 602 patients were
      examined to determine the rates of complications following lower limb
      arthroplasty for the 12-month periods prior to and following the publication of
      these guidelines. These were compared with data from the National Joint Registry
      (England and Wales) regarding the use of LMWH during the same periods. There was
      a significant increase in the reported use of LMWH (59.5% to 67.6%, p < 0.001)
      following the publication of the guidelines. However, the 90-day venous
      thromboembolism events actually increased slightly following total hip
      replacement (THR, 1.69% to 1.84%, p = 0.06) and remained unchanged following
      total knee replacement (TKR, 1.99% to 2.04%). Return to theatre in the first 30
      days for infection did not show significant changes. There was an increase in the
      number of patients diagnosed with thrombocytopenia, which was significant
      following THR (0.11% to 0.16%, p = 0.04). The recommendations from NICE are based
      on predicted reductions in venous thromboembolism events, reducing morbidity,
      mortality and costs to the NHS. The early results in orthopaedic patients do not
      support these predictions, but do show an increase in complications.

PMID- 20044691
TI  - Temporal trends in hip and knee replacement in the United Kingdom: 1991 to 2006.
AB  - Using the General Practice Research Database, we examined the temporal changes in
      the rates of primary total hip (THR) and total knee (TKR) replacement, the age at
      operation and the female-to-male ratio between 1991 and 2006 in the United
      Kingdom. We identified 27 113 patients with THR and 23 843 with TKR. The rate of
      performance of THR and TKR had increased significantly (p < 0.0001 for both)
      during the 16-year period and was greater for TKR, especially in the last five
      years. The mean age at operation was greater for women than for men and had
      remained stable throughout the period of study. The female-to-male ratio was
      higher for THR and TKR and had remained stable. The data support the notion that
      the rate of joint replacement is increasing in the United Kingdom with the rate
      of TKR rising at the highest rate. The perception that the mean age for TKR has
      decreased over time is not supported.

PMID- 20044692
TI  - A comparison of four systems for calibration when templating for total hip
      replacement with digital radiography.
AB  - We have investigated the accuracy of the templating of digital radiographs in
      planning total hip replacement using two common object-based calibration methods
      with the ball placed laterally (method 1) or medially (method 2) and compared
      them with two non-object-based methods. The latter comprised the application of a
      fixed magnification of 121% (method 3) and calculation of magnification based on
      the object-film-distance (method 4). We studied the post-operative radiographs of
      57 patients (19 men, 38 women, mean age 73 years (53 to 89)) using the measured
      diameter of the prosthetic femoral head and comparing it with the true value.
      Both object-based methods (1 and 2) produced large errors (mean/maximum:
      2.55%/17.4% and 2.04%/6.46%, respectively). Method 3 applying a fixed
      magnification and method 4 (object-film-distance) produced smaller errors
      (mean/maximum 1.42%/5.22% and 1.57%/4.24%, respectively; p < 0.01). The latter
      results were clinically relevant and acceptable when planning was allowed to
      within one implant size. Object-based calibration (methods 1 and 2) has
      fundamental problems with the correct placement of the calibration ball. The
      accuracy of the fixed magnification (method 3) matched that of object-film
      distance (method 4) and was the most reliable and efficient calibration method in
      digital templating.

PMID- 20044694
TI  - Fixator-assisted nailing and consecutive lengthening over an intramedullary nail
      for the correction of tibial deformity.
AB  - We report the results of using a combination of fixator-assisted nailing with
      lengthening over an intramedullary nail in patients with tibial deformity and
      shortening. Between 1997 and 2007, 13 tibiae in nine patients with a mean age of
      25.4 years (17 to 34) were treated with a unilateral external fixator for acute
      correction of deformity, followed by lengthening over an intramedullary nail with
      a circular external fixator applied at the same operating session. At the end of
      the distraction period locking screws were inserted through the intramedullary
      nail and the external fixator was removed. The mean amount of lengthening was 5.9
      cm (2 to 8). The mean time of external fixation was 90 days (38 to 265). The mean
      external fixation index was 15.8 days/cm (8.9 to 33.1) and the mean bone healing
      index was 38 days/cm (30 to 60). One patient developed an equinus deformity which
      responded to stretching and bracing. Another developed a drop foot due to a
      compartment syndrome, which was treated by fasciotomy. It recovered in three
      months. Two patients required bone grafting for poor callus formation. We
      conclude that the combination of fixator-assisted nailing with lengthening over
      an intramedullary nail can reduce the overall external fixation time and prevent
      fractures and deformity of the regenerated bone.

PMID- 20044693
TI  - Locked intramedullary nailing of symptomatic metastases in the humerus.
AB  - The humerus is a common site for skeletal metastases in the adult. Surgical
      stabilisation of such lesions is often necessary to relieve pain and restore
      function. These procedures are essentially palliative and should therefore
      provide effective relief from pain for the remainder of the patient's life
      without the need for further surgical intervention. We report a retrospective
      analysis of 35 patients (37 nails) with symptomatic metastases in the shaft of
      the humerus which were treated by locked, antegrade nailing. There were 27 true
      fractures (73.0%) and ten painful deposits (27.0%). Relief from pain was
      excellent in four (11.4%), good in 29 (82.9%) and fair in two (5.7%) on
      discharge. Function was improved in all but one patient. One case of palsy of the
      radial nerve was noted. The mean postoperative survival was 7.1 months (0.2 to
      45.5) which emphasises the poor prognosis in this group of patients. There were
      no failures of fixation and no case in which further surgery was required.
      Antegrade intramedullary nailing is an effective means of stabilising the humerus
      for the palliative treatment of metastases. It relieves pain and restores
      function to the upper limb with low attendant morbidity.

PMID- 20044695
TI  - Ruptured aneurysm of the common iliac artery as a cause of unilateral hip pain.
AB  - Rupture of an aneurysm of the common iliac artery is a rare cause of pain in the
      hip. We describe an elderly hypertensive patient with an aneurysmal rupture of
      the left common iliac artery who presented with unilateral hip pain masquerading
      as septic arthritis.

PMID- 20044696
TI  - Medial dislocation of the medial meniscus.
AB  - We present the first reported case of symptomatic medial dislocation of the
      medial meniscus in a patient who had no previous history of trauma and who had an
      otherwise normal knee. The treatment of instability of the medial meniscus is
      controversial and studies have indicated that certain individuals without a firm
      meniscal bony insertion may be predisposed to meniscal dislocation. In our
      patient, the meniscal instability interfered with daily activities. Operative
      stabilisation by reconstruction of the meniscotibial ligaments cured the
      symptoms.

PMID- 20044697
TI  - Evaluation and comparison of the antimicrobial efficacy of teicoplanin- and
      clindamycin-coated titanium implants: an experimental study.
AB  - We studied the effects of coating titanium implants with teicoplanin and
      clindamycin in 30 New Zealand White rabbits which were randomly assigned to three
      groups. The intramedullary canal of the left tibia of each rabbit was inoculated
      with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated
      implants were implanted into rabbits in group 1, clindamycin-coated implants into
      rabbits in group 2, and uncoated implants into those in group 3. All the rabbits
      were killed one week later. The implants were removed and cultured together with
      pieces of tibial bone and wound swabs. The rate of colonisation of the organisms
      in the three groups was compared. Organisms were cultured from no rabbits in
      group 1, one in group 2 but from all in group 3. There was no significant
      difference between groups 1 and 2 (p = 1.000). There were significant differences
      between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection
      against bacterial colonisation and infection was found with teicoplanin- and
      clindamycin-coated implants in this experimental model.

PMID- 20044698
TI  - Fracture of the clavicle does not affect arthritis of the ipsilateral
      acromioclavicular joint compared with the contralateral side: An osteological
      study.
AB  - In an osteological collection of 3100 specimens, 70 were found with unilateral
      clavicular fractures which were matched with 70 randomly selected normal
      specimens. This formed the basis of a study of the incidence of arthritis of the
      acromioclavicular joint and the effect of clavicular fracture on the development
      of arthritis in the ipsilateral acromioclavicular joint. This was graded visually
      on a severity scale of 0 to 3. The incidence of moderate to severe arthritis of
      the acromioclavicular joint in normal specimens was 77% (100 specimens). In those
      with a clavicular fracture, 66 of 70 (94%) had arthritis of the acromioclavicular
      joint, compared to 63 of 70 (90%) on the non-injured contralateral side (p =
      0.35). Clavicles with shortening of 15 mm or less had no difference in the
      incidence of arthritis compared to those with shortening greater than 15 mm (p =
      0.25). The location of the fracture had no effect on the development of
      arthritis.

PMID- 20044699
TI  - Enhancement of meniscal repair in the avascular zone using mesenchymal stem cells
      in a porcine model.
AB  - We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs)
      together with a conventional suturing technique would show improved healing
      compared with those treated by a conventional suturing technique alone. In a
      controlled laboratory study 28 adult pigs (56 knees) underwent meniscal
      procedures after the creation of a radial incision to represent a tear. Group 1
      (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19)
      the incision was repaired with sutures and fibrin glue and in group 3, the
      experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue. At
      eight weeks, macroscopic examination of group 1 showed no healing in any
      specimens. In group 2 no healing was found in 12 specimens and incomplete healing
      in seven. The experimental group 3 had 21 specimens with complete healing, five
      with incomplete healing and two with no healing. Between the experimental group
      and each of the control groups this difference was significant (p < 0.001). The
      histological and macroscopic findings showed that the repair of meniscal tears in
      the avascular zone was significantly improved with MSCs, but that the mechanical
      properties of the healed menisci remained reduced.

PMID- 20044700
TI  - Does the anteromedial or anterolateral approach alter the rate of joint puncture
      in injection of the ankle?: A cadaver study.
AB  - Injection or aspiration of the ankle may be performed through either an
      anteromedial or an anterolateral approach for diagnostic or therapeutic reasons.
      We evaluated the success of an intra-articular puncture in relation to its site
      in 76 ankles from 38 cadavers. Two orthopaedic surgical trainees each injected
      methylene blue dye into 18 of 38 ankles through an anterolateral approach and
      into 20 of 38 through an anteromedial. An arthrotomy was then performed to
      confirm the placement of the dye within the joint. Of the anteromedial injections
      31 of 40 (77.5%, 95% confidence interval (CI) 64.6 to 90.4) were successful as
      were 31 of 36 (86.1%, 95% CI 74.8 to 97.4) anterolateral injections. In total 62
      of 76 (81.6%, 95% CI 72.9 to 90.3) of the injections were intra-articular with a
      trend towards greater accuracy with the anterolateral approach, but this
      difference was not statistically significant (p = 0.25). In the case of trainee
      A, 16 of 20 anteromedial injections and 14 of 18 anterolateral punctures were
      intra-articular. Trainee B made successful intra-articular punctures in 15 of 20
      anteromedial and 17 of 18 anterolateral approaches. There was no significant
      difference between them (p = 0.5 and p = 0.16 for the anteromedial and
      anterolateral approaches, respectively). These results were similar to those of
      other reported studies. Unintended peri-articular injection can cause
      complications and an unsuccessful aspiration can delay diagnosis. Placement of
      the needle may be aided by the use of ultrasonographic scanning or fluoroscopy
      which may be required in certain instances.

PMID- 20044701
TI  - The use of a biodegradable mesh plate to augment grafting of an acetabular
      defect: Laboratory investigation and clinical pilot study.
AB  - We used a biodegradable mesh to convert an acetabular defect into a contained
      defect in six patients at total hip replacement. Their mean age was 61 years (46
      to 69). The mean follow-up was 32 months (19 to 50). Before clinical use, the
      strength retention and hydrolytic in vitro degradation properties of the implants
      were studied in the laboratory over a two-year period. A successful clinical
      outcome was determined by the radiological findings and the Harris hip score. All
      the patients had a satisfactory outcome and no mechanical failures or other
      complications were observed. No protrusion of any of the impacted grafts was
      observed beyond the mesh. According to our preliminary laboratory and clinical
      results the biodegradable mesh is suitable for augmenting uncontained acetabular
      defects in which the primary stability of the implanted acetabular component is
      provided by the host bone. In the case of defects of the acetabular floor this
      new application provides a safe method of preventing graft material from
      protruding excessively into the pelvis and the mesh seems to tolerate bone
      impaction grafting in selected patients with primary and revision total hip
      replacement.

PMID- 20044702
TI  - A magnetic resonance imaging investigation of the transversus abdominis muscle
      during drawing-in of the abdominal wall in elite Australian Football League
      players with and without low back pain.
AB  - STUDY DESIGN: Single-blinded quasi-experimental study. OBJECTIVE: To investigate
      the ability of elite football players with and without low back pain (LBP) to
      voluntarily draw-in the abdominal wall. BACKGROUND: While there has been
      considerable debate regarding the contribution of the transversus abdominis (TrA)
      muscle to control the lumbar spine and pelvis, there is evidence that retraining
      motor control of the deep trunk muscles is commensurate with decreases in LBP.
      Magnetic resonance imaging (MRI) has been used to assess the TrA muscle during
      the draw-in maneuver, with the contraction of the TrA muscle reducing the
      circumference of the trunk. Impairments in performance of the draw-in maneuver
      have been shown in people with LBP. METHODS: Forty-three elite players from a
      team in the Australian Football League were allocated to 3 groups: those with "no
      LBP," "a history of LBP but no current LBP," or "current LBP." MRI was used to
      image the cross-sectional area (CSA) of the trunk at the level of the L3-4 disc
      at the start and end of the draw-in maneuver. RESULTS: There was a significant
      decrease in the CSA of the trunk with the performance of the draw-in maneuver
      (P<.001). Subjects in the "no LBP" group were better able to "draw-in" the
      abdominal wall than subjects with current LBP (P = .015). CONCLUSIONS: This study
      provides evidence of an altered ability to draw-in the abdominal wall in
      footballers with current LBP. Retraining contraction of the TrA muscle may
      constitute one part of an exercise-therapy approach for athletes with current
      LBP.

PMID- 20044703
TI  - Description of clinical outcomes and postoperative utilization of physical
      therapy services within 4 categories of shoulder surgery.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To describe the clinical
      outcomes following outpatient physical therapy for postoperative rehabilitation
      in 4 categories of shoulder surgery. Furthermore, we sought to determine if
      differences in outcomes between genders existed. BACKGROUND: Improving the
      quality of care for patients following shoulder surgery requires an understanding
      of the clinical outcomes resulting from current clinical practice. METHODS: This
      study included 856 patients (43.7% female; mean +/- SD age, 51.8 +/- 14.2 years)
      who received outpatient physical therapy following shoulder surgery. Standardized
      methods for classification of patients to type of shoulder surgery and collection
      of outcome variables were used. Data were gathered from 57 therapists working in
      12 clinics. Patients included had been classified into 1 of 4 surgical
      categories: repair of a unidirectional instability, rotator cuff repair, rotator
      cuff repair with a subacromial decompression, or subacromial decompression alone.
      Descriptive statistics were calculated for baseline characteristics of patients
      in each surgical category. For all patients, scores on the Disability of the Arm
      Shoulder and Hand (DASH) questionnaire and a numeric pain rating scale (NPRS)
      were obtained at the initial and final physical therapy visits, and the change
      between visits was calculated. Data on number of physical therapy sessions and
      length of stay (LOS) were collected. For each surgical category, independent
      samples t tests were used to determine differences between genders for each
      initial and final clinical outcome of pain and disability, change scores,
      utilization of visits, and LOS. The percentage of patients who achieved a minimal
      clinically important difference (MCID) on the DASH was also determined for each
      surgical group. For each gender in each surgical category, paired t tests were
      used to determine if patients achieved significant change in pain and disability.
      RESULTS: Means for each clinical outcome for the initial and final pain and
      disability scores, change scores, and the percentage of patients that achieved an
      MCID are provided. Significant differences were observed between genders for
      clinical outcomes. In the group treated with unilateral instability repair, women
      reported significantly greater initial disability than men, and their DASH change
      scores were significantly greater. In the group that had rotator cuff repairs,
      women reported significantly greater disability initially and at the final follow
      up. In the group that had rotator cuff repairs combined with subacrominal
      decompression, women reported significantly greater disability initially and
      greater change in DASH scores. Females also reported greater change in their pain
      scores than males (P<.05). There were no significant differences between men and
      women in the subacromial decompression group (P<.05). There were no significant
      differences between genders for number of physical therapy visits or LOS. Men and
      women in each surgical category achieved clinically meaningful and statistically
      significant improvement for pain and disability during treatments (P<.01).
      Greater than 75% of patients achieved an MCID (15 points) on the DASH score in
      each surgical category (range, 75.6%-94.5%). CONCLUSIONS: Differences were
      observed between men and women in 4 postoperative surgical categories in each of
      the clinical outcomes but not for number of physical therapy visits or LOS.
      Statistically significant and clinically meaningful pain and disability
      improvements were reported for each gender within each shoulder category. Results
      from this study may help therapists estimate the prognosis of males and females
      receiving nonstandardized postoperative physical therapy in 4 different shoulder
      surgical categories. LEVEL OF EVIDENCE: Therapy, level 2b.

PMID- 20044705
TI  - An expanding delivery model helps clinicians access the literature.
AB  - One of the biggest challenges clinicians face is keeping abreast of new
      information that affects the evaluation and treatment of their patients. The
      Journal of Orthopaedic & Sports Physical Therapy (JOSPT) was created in 1979 with
      this mandate in mind, using the established technology of the day: print on
      paper. A recent survey of JOSPT's readers confirms that the print version of the
      Journal remains valuable as a means of delivering this critical information. Yet
      the same survey demonstrates that the electronic distribution of searchable
      Journal articles, along with supplemental information such as videos and
      downloadable slides, is gaining increased attention and use. The website has
      become a cost- and time-effective and efficient means of acquiring this
      knowledge, regardless of the reader's location. This editorial provides an
      overview of some of the features JOSPT offers online.

PMID- 20044704
TI  - Effects of a wobble board-based therapeutic exergaming system for balance
      training on dynamic postural stability and intrinsic motivation levels.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVES: To compare the effects of
      wobble board exercises with and without feedback provided through integrating the
      wobble board movement into a computer game system, by comparing changes in
      postural stability and motivation. BACKGROUND: Therapeutic exergaming systems may
      offer a solution to poor adherence to postural control exercise regimes by
      improving motivation levels during exercise performance. METHODS: Twenty-two
      healthy adults, randomly assigned to an exergaming group (n = 11) and a control
      group (n = 11), completed 12 exercise sessions. Dynamic postural stability was
      quantified at baseline and follow-up using the star excursion balance test and
      the dynamic postural stability index during a jump-landing task. Intrinsic
      motivation was measured at baseline using the Self-Motivation Inventory and at
      follow-up using the Intrinsic Motivation Inventory. RESULTS: Star excursion
      balance test scores showed a statistically significant (P<.008) improvement in
      the posteromedial and posterolateral direction for both groups. No within-group
      change for the dynamic postural stability index or between-group difference for
      star excursion balance test or dynamic postural stability index scores were
      observed. The "interest and enjoyment" category of the Intrinsic Motivation
      Inventory showed significantly higher scores (P<.001) in the exergaming group at
      follow-up, which was 1 of the 5 Intrinsic Motivation Inventory categories
      evaluated. CONCLUSIONS: The findings suggest that exercising with the therapeutic
      exergaming system showed similar improvements in dynamic postural stability and
      showed a greater level of interest and enjoyment when compared to a group doing
      similar balance training without the game system. LEVEL OF EVIDENCE: Therapy,
      level 2b.

PMID- 20044706
TI  - Radial head fracture following a fall.

PMID- 20044736
TI  - Automated microfluidic blood lysis protocol for enrichment of circulating
      nucleated cells.
AB  - In this report the protocol for an automated microfluidic blood lysis device is
      detailed. Circulating nucleated cells (CNCs), including leukocytes and
      endothelial cells, provide an ideal platform for an updated status on the immune
      condition of an individual. The microfluidic protocol allows for enrichment of
      CNCs without selective cell loss and sample preparation variability due to user
      mediated steps. Briefly, the protocol includes device fabrication, sample
      collection, device setup, and running blood through the microfluidic chamber.
      Within the device whole blood is rapidly mixed with deionized water for
      approximately 10 seconds in a 50 micron x 150 micron microfluidic channel. In
      this time span erythrocytes are lysed due to hypotonic conditions. Herringbone
      structures on the bottom of the channel ensure thorough mixing and exposure of
      cells to a constant environment. Remaining cells are returned to isotonic
      conditions at the exit of the device, fixed using 2% paraformaldehyde,
      centrifuged to separate erythrocyte debris from CNCs, and suspended in flow
      buffer for staining and analysis by flow cytometry. Results show clean flow
      cytometry scatter plots with CNC populations saved. Significance of this device
      and protocol comes in the study and understanding of disease pathogenesis by
      analysis of CNC populations. Hence, automation, effectiveness, and simplicity of
      the microfluidic protocol are demonstrated.

PMID- 20044738
TI  - Cross-sectional characterization of all classes of antihypertensives in terms of
      central blood pressure in Japanese hypertensive patients.
AB  - BACKGROUND: Central blood pressure (CBP) has been reported to be superior to
      brachial blood pressure (BP) as a cardiovascular risk predictor in hypertensive
      patients; however, the effects of antihypertensives on CBP have not been fully
      examined. This cross-sectional hypothesis-generating study aimed to tentatively
      characterize all classes of antihypertensives in relation to CBP. METHODS:
      Calibrated tonometric radial artery pressure waveforms were recorded using an
      automated device in 1,727 treated hypertensive patients and 848 nonhypertensive
      (non-HT) participants. Radial artery late systolic BP (SBP) has been reported to
      reflect central SBP. The difference between late and peak SBPs (DeltaSBP2) was
      assessed with linear regression model-based adjustments. Separate regression
      models for DeltaSBP2 were constructed for both participant groups as well as
      specified sub-populations. RESULTS: DeltaSBP2 was 3.3 mm Hg lower in patients
      treated with any single-vasodilating (VD) antihypertensive agent without
      significant interclass difference than with non-VD agents, and was 2.0 mm Hg
      lower than estimated in nonhypertensive subjects. Combinations of two
      vasodilators were 6.6 and 2.9 mm Hg lower in DeltaSBP2 than nonvasodilator
      combinations and nonhypertensive subjects, respectively (P < 0.001 for all
      comparisons). Nonvasodilators and their combination showed high DeltaSBP2, 1.1
      and 3.7 mm Hg higher than in nonhypertensive subjects (P < 0.001 for both).
      Additional adjustment of the pulse rate reduced high DeltaSBP2 with beta-blockers
      (betaBLs). CONCLUSIONS: This cross-sectional observation suggests that
      vasodilatory antihypertensives lower CBP independently of peripheral BP levels
      without evident class-specific differences, whereas nonvasodilators may raise
      CBP.

PMID- 20044737
TI  - Synopsis and data synthesis of genetic association studies in hypertension for
      the adrenergic receptor family genes: the CUMAGAS-HYPERT database.
AB  - BACKGROUND: The adrenergic receptor (adrenoceptor) family genes have been
      extensively studied as candidate genes in hypertension but the results of
      individual genetic association studies (GAS) are controversial and inconclusive.
      To clarify these data, a systematic assessment of GAS for adrenoceptor family
      genes in hypertension was conducted. METHODS: Data from 163 GAS involving 7 genes
      and 37 distinct genetic variants were analyzed and cataloged in CUMAGAS-HYPERT
      (Cumulative Meta-analysis of Genetic Association Studies-HYPERTension; a web
      based information system, which allows the retrieval and synthesis of data from
      GAS in hypertension, available at http://biomath.med.uth.gr). Data from genome
      wide association studies involving the adrenoceptor family genes were also
      systematically searched. RESULTS: Individual GAS reported inconsistent
      associations and had limited power to detect modest genetic effects, with only
      1.2% having power >80%. Thirteen variants were investigated by three or more
      studies and their results were subject to meta-analysis. In the main meta
      analyses, significant results were shown for five variants (ADRB1 p.Arg389Gly,
      ADRB1 p.Ser49Gly, ADRB2 g.9368308A>G, ADRB3 p.Trp64Arg, and ADRA1A p.Cys347Arg)
      under the allelic contrast and/or the dominant model. Subgroup analyses by
      ethnicity and gender detected significant associations for three variants (ADRB1
      p.Arg389Gly in east Asians, ADRB2 p.Gln27Glu in whites, and ADRB3 p.Trp64Arg in
      whites and in males). Heterogeneity ranged from none to high. No significant
      associations were recorded from genome-wide studies. CONCLUSIONS: There is
      evidence to implicate adrenoceptor genes in hypertension, although future studies
      designed to investigate epistatic and gene-environment interactions would allow
      more solid conclusions to be drawn about the role of these genes in hypertension.

PMID- 20044739
TI  - Additive interaction of metabolic syndrome and chronic kidney disease on cardiac
      hypertrophy, and risk of cardiovascular disease in hypertension.
AB  - BACKGROUND: Recent epidemiologic analyses have demonstrated a link between the
      metabolic syndrome (MetS) and chronic kidney disease (CKD). We examined the
      association between MetS, CKD, and left ventricular hypertrophy (LVH), and
      prospectively investigated the predictive value of the combination of MetS and
      CKD for cardiovascular disease (CVD) in essential hypertension. METHODS: A total
      of 1,160 essential hypertensive patients (mean age 63 years, 53% male) underwent
      clinical evaluation, laboratory testing, and Doppler echocardiography, and were
      monitored for a mean follow-up of 4.8 years. RESULTS: At baseline, total subjects
      were divided into four groups according to the presence/absence of MetS and/or
      CKD, and, compared to the group without MetS and CKD (MetS-/CKD-); those with
      MetS and CKD (MetS+/CKD+) had a multivariate-adjusted odds ratio of 2.40 (95%
      confidence interval (CI) 1.66-3.48) for LVH. During the follow-up period, 172
      subjects developed CVD. Multiple Cox regression analysis including LV mass index
      (LVMI) showed that the presence of MetS as well as that of CKD were each
      independent predictors of CVD (hazard ratio 1.90 for MetS, 1.82 for CKD). We then
      divided the total subjects into four groups, and found that, compared to the MetS
      /CKD- group, multivariate-adjusted HR for the MetS+/CKD+ group was 3.58 (95% CI
      2.14-5.95). CONCLUSIONS: Our findings suggest that, in essential hypertension,
      the combination of MetS and CKD is a strong risk for LVH as well as a strong and
      independent predictor of subsequent CVD. These findings highlight the clinical
      importance of the concomitance of MetS and CKD in essential hypertension.

PMID- 20044740
TI  - Effects of time of antihypertensive treatment on ambulatory blood pressure and
      clinical characteristics of subjects with resistant hypertension.
AB  - BACKGROUND: Subjects with resistant hypertension present high prevalence of a
      nondipper blood pressure (BP) pattern, associated with increased risk of
      cardiovascular events. Nondipping is partly related to the absence of 24-h
      therapeutic coverage in hypertensives treated with single morning doses. METHODS:
      We studied the impact of treatment time on ambulatory BP and clinical
      characteristics of 1,794 subjects with resistant hypertension, categorized
      according to the time of treatment (either ingesting all antihypertensive
      medications upon awakening, or > or =1 drug at bedtime). BP was measured for 48
      consecutive hours, and physical activity was simultaneously monitored every
      minute by wrist actigraphy. RESULTS: The percentage of controlled subjects was
      higher among those taking medication at bedtime (P < 0.001). Among the 1,306
      participants with true resistant hypertension, those ingesting > or =1 drug at
      bedtime showed significantly lower 24-h mean of systolic BP (SBP)/diastolic BP
      (DBP) (by 4.1/1.5 mm Hg, respectively; P < 0.015). The difference between groups
      was more prominent in asleep BP (9.7/4.4 mm Hg, P < 0.001). The awake/asleep BP
      ratio was significantly higher by 5.8% (P < 0.001) and the prevalence of
      nondipping lower from 83 to 40% (P < 0.001) in subjects receiving bedtime
      treatment. This latter group also showed significant lower mean values of
      glucose, total cholesterol, low-density lipoprotein-cholesterol, fibrinogen, and
      urinary albumin excretion. CONCLUSIONS: In resistant hypertension,
      pharmacological therapy should take into account when to treat with respect to
      the rest-activity cycle of each subject. Bedtime treatment was associated with
      greater clinic and ambulatory BP control, lower prevalence of a high-risk
      nondipper pattern, and lower values of relevant clinical markers of
      cardiovascular risk.

PMID- 20044741
TI  - Early left ventricular mechanics abnormalities in prehypertension: a two
      dimensional strain echocardiography study.
AB  - BACKGROUND: Prehypertension predicts established hypertension. In this study, the
      aim was to analyze left ventricular (LV) mechanics in borderline prehypertensive
      (pre-HT) and hypertensive (HT) subjects through two-dimensional (2D)-strain
      echocardiography and then evaluate possible relations between cardiac parameters
      and insulin metabolism (homeostasis model assessment of insulin resistance
      (HOMA(IR)). METHODS: Seventy-four consecutive newly diagnosed, untreated HT were
      divided, on the basis of their office blood pressure (BP) measurements, confirmed
      by ambulatory BP monitoring (ABPM), in 41 borderline pre-HT (ABPM: 122.5 +/-
      6.7/76.2 +/- 5.2 mm Hg) and 33 never-treated mild HT (ABPM: 138.3 +/- 7.3/87.6 +/
      7.1 mm Hg). Thirty-three healthy normotensive (NT) controls (ABPM: 114.8 +/-
      6.3/73.1 +/- 6.1 mm Hg) (P < 0.0001) were also studied (NT). All subjects
      performed 2D color Doppler and pulsed-wave tissue Doppler imaging (PW-TDI).
      RESULTS: Left ventricular mass (LVM) was significantly higher in pre-HT (39.2 +/-
      8.7 g/m(2.7)) and in HT (43.6 +/- 8.5 g/m(2.7)) compared with NT (30.9 +/- 7.4
      g/m(2.7)) (P < 0.0001). A mild LV diastolic dysfunction was found both with
      Doppler mitral flow velocity and PW-TDI at mitral annulus level analysis.
      Longitudinal 2D strain in pre-HT (-18.9% +/- 3.4) and in HT (-18.0% +/- 3.3) was
      significantly lower than in NT (-23.9% +/- 3.0) (P < 0.002). These LV
      abnormalities were associated with systolic ABPM, LVM, and HOMA(IR). CONCLUSIONS:
      Early abnormalities of LV longitudinal systolic deformation were found both in
      pre-HT and HT, together with a mild LV diastolic dysfunction. In both groups this
      early cardiac systolic and diastolic dysfunction is associated to insulin
      resistance, systolic pressure load, and cardiac remodeling.

PMID- 20044743
TI  - Gene action of canopy temperature in bread wheat under diverse environments.
AB  - While canopy temperature (CT) shows a strong and reliable association with yield
      under drought and heat stress and is used in wheat breeding to select for yield,
      little is known of its genetic control. The objective of this study was to
      determine the gene action controlling CT in five wheat populations grown in
      diverse environments (heat, drought, and well-irrigated conditions). CT showed
      negative phenotypic correlations with grain yield under drought and well
      irrigated environments. Additive x additive effects were most prevalent and
      significant for all crosses and environments. Dominance and dominance x dominance
      gene actions were also found, though the significance and direction was specific
      for each environment and genotypic cross. The use of CT as a selection criterion
      to improve tolerance to drought was supported by its significant association with
      grain yield and the genotype differences observed between cultivars. Our results
      indicated that genetic gains for CT in wheat could be achieved through
      conventional breeding. However, given some dominance and epistatic effects, it
      would be necessary to delay the selection process until the frequency of
      heterozygous loci within families is reduced.

PMID- 20044742
TI  - Decreased NKCC1 activity in erythrocytes from African Americans with hypertension
      and dyslipidemia.
AB  - BACKGROUND: Recent studies demonstrated a key role of ubiquitous isoform of
      Na+,K+,2Cl- co-transport (NKCC1) in regulation of myogenic tone and peripheral
      resistance. We examined the impact of race, gender, and plasma lipid on NKCC1
      activity in French Canadians and African Americans with hypertension and
      dyslipidemia. METHODS: NKCC and passive erythrocyte membrane permeability to K+,
      measured as ouabain-resistant, bumetanide-sensitive, and (ouabain+bumetanide)
      resistant 86Rb influx, respectively, were compared in 111 French-Canadian men,
      107 French-Canadian women, 26 African-American men, and 45 African-American women
      with essential hypertension and dyslipidemia. RESULTS: The African-American men
      and women were 7 years younger and presented twofold decreased plasma
      triglycerides compared to their French-Canadian counterparts (P < 0.01) whereas
      body mass index (BMI), total cholesterol, low-density lipoprotein, and high
      density lipoprotein (HDL) were not different. NKCC was respectively 50 and 38%
      lower in the African-American men and women than in the French Canadians (P <
      0.005) without any differences in passive erythrocyte membrane permeability for
      K+. We did not observe any impact of age on NKCC in all groups under
      investigation, whereas plasma triglycerides correlated positively with the
      activity of this carrier in the French-Canadian men only. CONCLUSIONS: NKCC1
      activity is lower in erythrocytes of African Americans with essential
      hypertension and dyslipidemia than in Caucasian counterparts. We suggest that
      decreased NKCC1 may contribute to the feature of the pathogenesis of salt
      sensitive hypertension seen in African Americans.

PMID- 20044744
TI  - Distribution and potential human risk of organochlorine pesticides in market
      mollusks from Dalian, China.
AB  - Levels of organochlorine pesticides (OCPs) were analyzed in mollusk samples
      collected from markets in Dalian, China. Among 14 OCPs screened, chlordane
      (Chls), dichlorodiphenyltrichloroethane (DDT) and 1,2,3,4,5,6
      hexachlorocyclohexane (HCH) were dominant compounds with the medians of 30.2,
      5.31 and 2.03 ng/g wet weight (ww), respectively. Source analysis showed that,
      much higher concentrations of Chls in mollusk samples were the result of usage of
      the chemical in the city, HCH in samples were mainly due to historical technical
      HCH usage, and a small amount of fresh use of DDT might exist, causing high
      portion of p,p'-DDT in samples. Cumulative distribution functions for the
      concentrations of the selected OCPs were compared to several threshold criteria,
      indicating that concentrations in most mollusk samples were lower than the safe
      lines. The concentration data of selected OCPs were used for risk assessment, and
      human exposure levels were compared to noncancer and cancer benchmarks.

PMID- 20044745
TI  - Effect of sensory inputs on the soleus H-reflex amplitude during robotic passive
      stepping in humans.
AB  - We investigated the modulation of the soleus (Sol) Hoffmann (H-) reflex
      excitability by peripheral sensory inputs during passive stepping using a robotic
      driven gait orthosis in healthy subjects and spinal cord-injured patients. The
      Sol H-reflex was evoked at standing and at six phases during passive stepping in
      40 and 100% body weight unloaded conditions. The Sol H-reflex excitability was
      significantly inhibited during passive stepping when compared with standing
      posture at each unloaded condition. During passive stepping, the H-reflex
      amplitude was significantly smaller in the early- and mid-swing phases than in
      the stance phase, which was similar to the modulation pattern previously reported
      for normal walking. No significant differences were observed in the H-reflex
      amplitude between the two unloaded conditions during passive stepping. The reflex
      depression observed at the early part of the swing phase during passive stepping
      might be attributed to the sensory inputs elicited by flexion of the hip and knee
      joints. The present study provides evidence that peripheral sensory inputs have a
      significant role in phase-dependent modulation of the Sol H-reflex during
      walking, and that the Sol H-reflex excitability might be less affected by load
      related afferents during walking.

PMID- 20044747
TI  - Effects of metal exposure on associative learning behavior in nematode
      Caenorhabditis elegans.
AB  - In the present study, the thermotaxis model was used to evaluate the effects of
      metal exposure at different concentrations on associative learning behavior in
      nematodes. The examined nematodes were cultured at 25 or 17 degrees C, and then
      shifted to 20 degrees C condition. Based on the ability of nematodes to trace the
      temperature of 20 degrees C, exposure to 10 microM of all examined metals and 2.5
      microM Pb and Hg caused significant decrease of associative learning behavior at
      time intervals of 5 and 18 h; however, exposure to 2.5 microM Cu, Zn, and Ag did
      not influence associative learning behavior. Moreover, exposure to 2.5 and 10
      microM of examined metals did not influence body bend and thermotaxis to
      cultivation temperature, whereas exposure to 50 microM of examined metals caused
      significant reduction of body bend and thermotaxis to cultivation temperature.
      Furthermore, Pb and Hg were the more toxic among the examined metals, with severe
      toxicity on associative learning behavior, thermotaxis, and locomotion behavior
      in nematodes.

PMID- 20044746
TI  - Distorting the visual size of the hand affects hand pre-shaping during grasping.
AB  - Vision of the body is known to affect somatosensory perception (e.g.
      proprioception or tactile discrimination). However, it is unknown whether visual
      information about one's own body size can influence bodily action. We tested this
      by measuring the maximum grip aperture (MGA) parameter of grasping while eight
      subjects viewed a real size, enlarged or shrunken image of their hand reaching to
      grasp a cylinder. In the enlarged view condition, the MGA decreased relative to
      real size view, as if the grasping movement was actually executed with a
      physically larger hand, thus requiring a smaller grip aperture to grasp the
      cylinder. Interestingly, MGA remained smaller even after visual feedback was
      removed. In contrast, no effect was found for the reduced view condition. This
      asymmetry may reflect the fact that enlargement of body parts is experienced more
      frequently than shrinkage, notably during normal growth. In conclusion, vision of
      the body can significantly and persistently affect the internal model of the body
      used for motor programming.

PMID- 20044748
TI  - HCH and DDT in sediments from marine and adjacent riverine areas of North Bohai
      Sea, China.
AB  - Residues of organochlorine pesticides (OCPs), hexachlorocyclohexanes (HCHs), and
      dichlorodiphenyltrichloroethanes (DDTs) and their environmental risks in surface
      sediments collected from marine and adjacent riverine/estuarine areas in the
      northern Bohai Sea, China, were investigated. Concentrations of SigmaHCH and
      SigmaDDT in sediments ranged from below detection (<LOD) to 1964.97 ng g(-1) dry
      wt (dw; mean, 92.51 ng g(-1) dw) and <LOD to 86.46 ng g(-1) dw (mean, 9.23 ng g(
      1) dw), respectively. Concentrations of HCH and DDT were generally higher in
      marine than riverine sediments. Concentrations of HCH and DDT residues found in
      the present study were higher than those reported in marine and river/estuary
      sediments from other areas of the world. The source of HCH in sediments could be
      explained by the large amount of historical use, while DDT seemed to be a
      combination of erosion of the weathered soils and long-range atmospheric
      transport. Concentrations of HCH in sediments from the study areas did not exceed
      sediment quality guidelines (SQGs), with the exception of gamma-HCH. However,
      risks posed by concentrations of DDT observed in sediments were found to be
      moderate to high compared with those posed by consensus-based SQGs. Although the
      mean sedimentary concentrations of HCH and DDT found in the area of the northern
      Bohai Sea, China were lower than suggested SQGs in general, their concentrations
      in some locations were close to or above the SQGs for adverse effects in benthic
      organisms and, thus, remain a cause for concern.

PMID- 20044749
TI  - Prediction of LT4 replacement dose to achieve euthyroidism in subjects undergoing
      total thyroidectomy for benign thyroid disorders.
AB  - BACKGROUND: Total thyroidectomy is becoming the preferred choice of treatment in
      patients with benign disorders of the thyroid gland; hence, an optimal method of
      replacing thyroxine is essential to avoid the ill effects of over- and under
      replacement of thyroxine in such patients. PATIENTS AND METHODS: We analyzed
      three methods of thyroxine replacement: replacement per kilogram of lean body
      mass (LBM) (2.5 mcg/kg LBM per day), per kilogram of body weight (1.6 mcg/kg body
      weight per day), and empirical replacement of thyroxine. RESULTS: The thyroxine
      requirement in thyroidectomized patients was 2.04 mcg/kg per day, with an
      increasing requirement of thyroxine with increments of weight. On multivariate
      analysis we found that the thyroxine requirement was strongly correlated both
      with body surface area (BSA) and with body weight. On subsequent correlation
      testing, we found that BSA was more strongly associated than weight with the
      thyroxine requirement. CONCLUSIONS: Patients undergoing total thyroidectomy may
      require higher doses of thyroxine to achieve euthyroidism when compared to
      patients with similar anthropometric parameters having primary hypothyroidism.
      The method of replacing thyroxine based on LBM is the ideal method, but
      replacement based on fixed-dose regimens could be a good method if the body
      weight is taken into consideration.

PMID- 20044750
TI  - Intravenous paclitaxel against metastasis of human gastric tumors of diffuse
      type.
AB  - PURPOSE: Gastric cancer is one of the leading cancerous diseases worldwide. It is
      diagnosed often at the advanced stage for which chemotherapy is the main
      treatment option. The prognosis remains poor for metastatic, especially the
      diffuse type, gastric cancers. We investigated the efficacy of intravenously
      administered paclitaxel treating metastases of locally disseminated gastric
      tumors of diffuse type. METHODS: Transfection of green fluorescent proteins (GFP)
      expressing plasmid into human gastric cancer MKN45 cells of diffuse type was
      performed, and MKN45-GFP cells constitutively expressing GFP were isolated. The
      MKN45-GFP cells were orthotopically inoculated into the mouse peritoneal cavity,
      and tumor growth and organ metastases were monitored. Liver metastases were
      harvested, re-inoculated, monitored for liver metastases again, and harvested for
      further inoculation. This in vivo selection procedure was repeated to isolate a
      subline with high metastatic abilities demonstrated by in vitro invasion
      abilities using Transwell((R)) system. By visualizing the GFP-expressing tumors,
      the effects of intravenously administered paclitaxel against the growing
      peritoneally disseminated and metastasized tumors in nude mice without laparotomy
      were measured. RESULTS: An in vivo selected gastric cancer cell line MKN45-GFP
      ip4 with high metastatic ability was established. Its invasion ability was
      inhibited by paclitaxel treatments in vitro. The growths of metastatic and
      intraperitoneally disseminated MKN45-GFP-ip4 tumors were significantly suppressed
      by intravenous paclitaxel treatments in nude mice. CONCLUSIONS: We found that
      intravenous paclitaxel is active against the metastases of human gastric cancer
      of peritoneal diffuse type, which warrants further investigations on optimizing
      the perioperative regimens with intravenous paclitaxel therapy for gastric cancer
      in patients.

PMID- 20044751
TI  - Pharmacokinetics of orally administered ABT-751 in children with neuroblastoma
      and other solid tumors.
AB  - PURPOSE: To describe the pharmacokinetics of orally administered ABT-751 and its
      conjugated metabolites in children with neuroblastoma and other solid tumors and
      to relate pharmacokinetic parameters to toxicity and therapeutic outcomes.
      METHODS: Patients (median age, 11 years) with neuroblastoma (n = 37) or other
      solid tumors (n = 25) had pharmacokinetic sampling after the first dose of ABT
      751 (75-250 mg/m(2)/day) on a 7-day or 21-day schedule. ABT-751 and its
      glucuronide and sulfate metabolites were quantified with an HPLC/MS/MS assay.
      Pharmacokinetic parameters were derived with non-compartmental methods. The
      relative bioavailability of more water soluble capsule and suspension
      formulations was assessed. RESULTS: ABT-751 peaked in plasma at 2 h and declined
      monoexponentially with a t (1/2) of 5.1 h. The apparent clearance was 33
      ml/min/m(2) and was age-independent. The AUC(0-infinity) increased in proportion
      to the dose, and at 200 mg/m(2) the median AUC(0-infinity) was 91 mcg h/ml and
      the C (ave) was 3.9 mcg/ml. Inter-and intra-patient variability was low. The
      metabolites were detected in plasma 30 min post-dose and peaked 3-5 h after the
      dose. The glucuronide:sulfate molar AUC(0-infinity) ratio was 0.57. Less than 1%
      of the dose was excreted in urine as parent drug; 13% of the dose was excreted as
      sulfate metabolite and 10% as glucuronide metabolite. The relative
      bioavailability of the water soluble capsule and suspension formulations was 105
      and 93%, respectively. AUC(0-infinity) was higher in patients experiencing dose
      limiting toxicity. CONCLUSIONS: Oral ABT-751 pharmacokinetics was dose
      proportional and age-independent with minimal intra- and inter-patient
      variability in children.

PMID- 20044752
TI  - Oncologic control obtained after exclusive flexible ureteroscopic management of
      upper urinary tract urothelial cell carcinoma.
AB  - OBJECTIVE: To assess oncological outcome after first-line management of upper
      urinary tract urothelial cell carcinomas (UUT-UCCs) by exclusive flexible
      ureteroscopy. MATERIALS AND METHODS: A retrospective review was performed for 35
      patients treated between 2003 and 2007. All patients underwent retrograde
      flexible ureteroscopy for diagnosis, treatment (i.e., holmium:YAG vaporisation),
      and follow-up. The following data were reviewed: sex, age, ASA score, presence of
      a solitary kidney, unifocal or multifocal tumour, history of bladder cancer,
      tumour localisation, tumour size, stage and grade, outcome, recurrence, and
      progression. RESULTS: The mean age was 67 + or - 13.1 years (range: 38-88). The
      tumour involved the renal pelvis and the caliceal system in 19 cases (54%), the
      ureter in 8 cases (23%), and both in 8 cases (23%). Twelve patients (34%) had a
      history of bladder carcinoma. Tumour stage was superficial in 63% (57% were pTa
      and 6% were pT1) and not available in 37%. Tumour grade was low, high, and
      unavailable in 49, 14, and 37%, respectively. The median follow-up was 30 months
      (range: 12-66), and 21 patients had a recurrence (60%). The median survival rate
      without recurrence was 10 months (95% CI [5-22]). Four patients underwent
      nephroureterectomy during follow-up. No patient died of disease progression. The
      main limitation was the limited length of follow-up. CONCLUSIONS: Flexible
      endoscopic management can be advocated in selected cases of non-muscle invasive
      UUT-UCCs as an alternative to nephroureterectomy. Because of a high recurrence
      rate, long-term and stringent surveillance is needed, including iterative
      ureteroscopies at least every 3 months for 2 years.

PMID- 20044753
TI  - Effects of fresh and seawater ingestion on osmoregulation in Atlantic bottlenose
      dolphins (Tursiops truncatus).
AB  - Bottlenose dolphins (Tursiops truncatus) are marine mammals with body water needs
      challenged by little access to fresh water and constant exposure to salt water.
      Osmoregulation has been studied in marine mammals for a century. Research
      assessing the effects of ingested fresh water or seawater in dolphins, however,
      has been limited to few animals and sampling times. Nine 16- to 25-h studies were
      conducted on eight adult dolphins to assess the hourly impact of fresh water,
      seawater, and seawater with protein ingestion on plasma and urine osmolality,
      urine flow rate (ufr), urinary and plasma solute concentrations, and solute
      clearance rates. Fresh water ingestion increased ufr. Fresh water ingestion also
      decreased plasma and urine osmolality, sodium and chloride urine concentrations,
      and solute excretion rates. Seawater ingestion resulted in increased ufr, sodium,
      chloride, and potassium urine concentrations, sodium excretion rates, and urine
      osmolality. Seawater with protein ingestion was associated with increased ufr,
      plasma osmolality, sodium excretion, and sodium, chloride, potassium, and urea
      urine concentrations. In conclusion, bottlenose dolphins appear to maintain water
      and plasma solute balance after ingesting fresh water or seawater by altering
      urine osmolality and solute clearance. Ingestion of protein with seawater appears
      to further push osmoregulation limits and urine solute concentrations in
      dolphins.

PMID- 20044754
TI  - The transition in hemoglobin proton-binding characteristics within the basal
      actinopterygian fishes.
AB  - Carbon dioxide (CO(2)) transport in the blood of fishes is aided by the proton
      binding properties of hemoglobin (Hb) through either a high-intrinsic buffer
      value and small oxylabile proton binding (Haldane effect), or a low buffer value
      and large Haldane effect. Primitive species, such as elasmobranchs and
      sarcopterygians have been shown to rely on the former, while derived species,
      such as teleosts rely on the latter. Both strategies are effective in the
      transport of CO(2) in the blood. However, there is a paucity of information on
      the nature of the transition between these two strategies that appears to occur
      within the intermediate group of fishes, the basal actinopterygians. The
      objective of the present study was to simultaneously assess the intrinsic Hb
      buffer values and Haldane effects of species within the basal actinopterygian
      lineage to characterize the transition in Hb-proton-binding strategy seen among
      the fishes. Expressed in order of most basal to most derived, the species
      investigated included American paddlefish (Polyodon spathula), white sturgeon
      (Acipenser transmontanus), spotted gar (Lepisosteus oculatus), alligator gar
      (Atractosteus spatula), bowfin (Amia calva), and mooneye (Hiodon tergisus).
      Hemolysates from these species were prepared and Hb titrations (under oxygenated
      and deoxygenated conditions) were performed in both the presence and absence of
      saturating levels of organic phosphates (GTP). The findings suggest that the
      nature of the Hb-proton-binding transition may have been punctuated rather than
      gradual, with the Hb buffer value decreasing and the Haldane effect increasing
      significantly in bowfin from fairly steady ancestral levels in the four more
      basal species. This change is coupled with the initial appearance of the choroid
      rete, as well as an increase in the magnitude and onset pH of the Root effect in
      bowfin, suggesting that the change in Hb-proton-binding strategy may be
      associated with the evolution of enhanced O(2) delivery to the eye and an in vivo
      operational Root effect.

PMID- 20044756
TI  - Mutant IDH1-specific immunohistochemistry distinguishes diffuse astrocytoma from
      astrocytosis.

PMID- 20044755
TI  - Association of molecular alterations, including BRAF, with biology and outcome in
      pilocytic astrocytomas.
AB  - Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population.
      PAs can exhibit variable behavior that does not always correlate with location.
      Although oncogenic rearrangements of the BRAF gene have recently been described
      in PAs, it is not clear whether such alterations have an impact on outcome. An
      institutional cohort of 147 PAs (118 with outcome data) from both cerebellar and
      non-cerebellar locations (spine, diencephalon, midbrain, brainstem, and cortex)
      was utilized in this study. Parameters included quantification of characteristic
      morphologic variables as well as genes and molecular loci previously shown to be
      of relevance in high-grade gliomas, including 1p, 9p, 10q, 17p, 19q, and BRAF.
      Neither 1p, 9p, and 10q nor 19q showed significant association with outcome in
      PAs, although p16 deletion was more common in PAs of the midbrain, brainstem, and
      spinal cord. Loss of heterozygosity on 17p13 correlated with increased risk of
      recurrence in cerebellar tumors. BRAF gene rearrangements were more common in
      cerebellar tumors than non-cerebellar tumors and associated with classic biphasic
      histology in the cerebellum. However, clinical outcome was independent of BRAF
      status. The molecular biology of PAs differs according to location, yet BRAF
      rearrangements do not appear to produce PAs with different behavior.
      Nevertheless, such tumors may have altered sensitivity to pathway-specific
      adjuvant therapy. Additionally, deletion on 17p13 may be an adverse prognostic
      biomarker in cerebellar tumors.

PMID- 20044758
TI  - Reproducibility of three-dimensional power Doppler placental vascular indices in
      pregnancies between 26 and 35 weeks.
AB  - PURPOSE: Assess intra and interobserver reproducibility of three-dimensional
      power Doppler (3DPD) placental vascular indices in normal pregnancies between 26
      and 35 weeks. METHODS: Thirty 3D volumes were captured by one observer and stored
      for analysis. Vascularization index (VI), flow index (FI) and vascularization
      flow index (VFI) were calculated from the spherical placental tissue samples
      obtained through the automatic Virtual Organ Computer-aided AnaLysis (VOCAL). Two
      observers analyzed the stored volumes and calculated the indices and their
      findings were compared. Intraclass correlation coefficients (ICCs) were used to
      analyze intra and interobserver correlations. Data were analyzed using confidence
      intervals, reliability coefficients and Bland-Altman graphs with concordance
      limits. RESULTS: All three indices had good intra and interobserver
      reproducibility. Intraobserver ICCs for the three indices were > 0.90. The FI had
      the highest ICC (0.99), the highest interobserver ICC (0.98) and the best
      concordance on the Bland-Altman graphs. CONCLUSION: 3DPD placental vascular
      indices obtained using the automatic sphere mode had a good intra and
      interobserver reproducibility for pregnancies between 26 and 35 weeks. The FI
      obtained the highest reproducibility scores.

PMID- 20044757
TI  - Effect of milk and calcium supplementation on bone density and bone turnover in
      pregnant Chinese women: a randomized controlled trail.
AB  - OBJECTIVE: Calcium demand is increased during pregnancy. However, few randomized
      controlled trials examined the effects of calcium supplementation on bone mass
      during pregnancy. This study determined effects of calcium and milk
      supplementation on maternal bone mineral density (BMD) and bone turnover in
      pregnant Chinese women with habitual low calcium intake. METHODS: In this
      randomized controlled trial, 36 Chinese pregnant women (24-31 years, 18
      gestational weeks) were randomly assigned to the following three arms (12 each):
      I, usual diet; II, "I" + 45 g milk powder (containing 350 mg calcium); or III,
      "II" + 600 mg calcium/day from gestational age of 20 weeks to 6 weeks post-partum
      (PP). BMD was measured post-treatment using dual-energy X-ray absorptiometry.
      Dietary intakes, 24-h urinary calcium, bone resorption (urinary hydroxyproline)
      and formation (serum osteocalcin) biomarkers were examined at the gestational age
      of 20 and 34 weeks, and 6 weeks PP. RESULTS: A dose-dependent relationship was
      observed between calcium intake and BMDs. The BMD values were significantly
      higher in subjects with calcium and milk supplementation than those in the
      controls at the whole body and spine (p < 0.05) but not at the hip sites. We
      found significant decreases in changes of urinary hydroxyproline, and significant
      increases in serum osteocalcin during the intervention period in the calcium/milk
      intervention groups than those in the control group (all p < 0.05). CONCLUSION:
      Calcium/milk supplementation during pregnancy is associated with greater BMD at
      the spine and whole body and suppresses bone resorption in Chinese women with
      habitual low calcium intake.

PMID- 20044759
TI  - Auditory discrimination training for tinnitus treatment: the effect of different
      paradigms.
AB  - Acoustic deprivation, i.e. hearing loss, is responsible for a cascade of
      processes resulting in reorganisation of the cortex. Tinnitus mechanisms are
      explained by synchronization of the neural spontaneous activity and might be
      related to cortical re-mapping. Auditory discrimination training (ADT) has
      demonstrated in both animals and humans to induce tonotopical changes in the
      auditory pathways through neural plasticity. We hypothesize that ADT could have
      some effect on tinnitus perception. The objective of this study is to compare the
      effect on tinnitus following two paradigms of ADT. Only patients from 20 to 60
      years of age were recruited. Inclusion criteria were pure tone tinnitus of mild
      or moderate handicap according to the Tinnitus Handicap Inventory score (<56).
      ADT patients were randomized in two groups: SAME (ADT in the same frequency of
      tinnitus pitch, 20 patients) and NONSAME (ADT in the frequency one-octave below
      tinnitus pitch, 21 patients). Groups of pair of tones (70% standard tones ST, 30%
      deviant tones ST + 0.1-0.5 kHz) were randomly mixed for 20 min/day during 1
      month. Patient had to mark when the two sounds of the pair were similar or
      different. Control group included 26 patients from the waiting list (WLG).
      Patients were also divided according to the trained frequency and the deepest
      hearing-impaired frequency. Outcome parameters were set up according to the
      answer to the question "is your tinnitus better, same, or worse with the
      treatment?" (RESP), the tinnitus handicap inventory (THI) and the visual analogue
      scale from 1 to 10 on tinnitus intensity (VAS). Tinnitus improved in 42.2% of the
      patients (RESP). VAS and THI scores were reduced but only THI differences were
      statistically significant (P = 0.003). ADT patients improved significantly
      compared with WLG in RESP and THI scores (P < 0.01). Training frequencies one
      octave below the tinnitus pitch (NONSAME) decreased significantly THI scores
      compared with patients trained frequencies similar to tinnitus pitch (SAME, P =
      0.035). RESP and VAS scores decreased more in NONSAME group though differences
      were not significant. We did not find any differences when comparing the group
      training the deepest hearing-impaired frequency and the group who trained other
      frequencies. Auditory discrimination training significantly improved tinnitus
      handicap compared to a waiting list group. Those patients who trained frequencies
      one octave below the tinnitus pitch had better outcome than those who performed
      the ADT with frequencies similar to the tinnitus pitch (P = 0.035).

PMID- 20044760
TI  - Prognostic impact of microRNA-related gene polymorphisms on survival of patients
      with colorectal cancer.
AB  - PURPOSE: The polymorphisms in microRNA (miRNA) machinery genes and miRNA
      containing genomic regions may play an important role in cancer development and
      prognosis. Accordingly, the present study analyzed the single nucleotide
      polymorphisms (SNPs) of miRNA-related genes and their impact on the prognosis for
      patients with colorectal cancer. METHODS: Four hundred and twenty-six consecutive
      patients with surgically treated colorectal adenocarcinoma were enrolled. The
      genomic DNA was extracted from fresh colorectal tissue and 40 polymorphisms of
      miRNA-related genes determined using a real-time PCR genotyping assay. RESULTS:
      In a univariate analysis, the progression-free survival of the patients with the
      combined mir492 C/G and G/G genotype was significantly worse than that of the
      patients with the mir492 C/C genotype (rs2289030) (P value = 0.0426), although
      there was no difference in the overall survival. However, no association was
      noted between the SNPs of the miRNA-related genes evaluated and survival in a
      multivariate analysis. CONCLUSIONS: None of the 40 miRNA-related gene
      polymorphisms investigated in this study was found to be an independent
      prognostic marker for Korean patients with surgically resected colorectal cancer.
      However, further studies are warranted to clarify the role of miRNA-related gene
      polymorphisms as a prognostic biomarker for colorectal cancer patients.

PMID- 20044761
TI  - Laparoscopic resection with intracorporeal anastomosis for colon carcinoma
      located in the splenic flexure.
AB  - BACKGROUND: Treatment of splenic flexure (SF) colon cancer is not standardized. A
      laparoscopic approach is considered a challenging procedure. METHODS: This review
      examines a single-institution experience with laparoscopic colon resection for
      cancer of the SF. Intraoperative, pathologic, and postoperative data of patients
      who underwent laparoscopic SF resection were reviewed to assess for oncologic
      safety as well as early- and medium-term outcomes. RESULTS: Between September
      2004 and January 2009, laparoscopic SF resection was performed for 15 patients
      with SF. Two cases of conversion were reported, and for three patients, colonic
      resection was robot assisted. In all cases, the anastomosis was completed
      intracorporeally. The distal margin was 3.8 +/- 2.5 cm, and the proximal margin
      was 7.8 +/- 3.7 cm from the tumor site. The mean number of harvested nodes was
      9.2 +/- 5.3. The mean operative time was 183.6 +/- 45 min, and the blood loss was
      98 +/- 33 ml. No major morbidity was recorded. CONCLUSIONS: Laparoscopic partial
      resection seems to be feasible and safe for the treatment of early-stage and
      locally advanced SF cancer.

PMID- 20044763
TI  - Matching groups for studying postoperative nausea and vomiting: should we care?

PMID- 20044764
TI  - Evaluation of the role of preoperative Double-J ureteral stenting in
      retroperitoneal laparoscopic pyelolithotomy.
AB  - BACKGROUND: Since the first retroperitoneal laparoscopic pyelolithotomy (RPPL)
      was reported by Gaur and associates in 1994, its technique has improved
      considerably. The applicability and indications of the procedure are expanding
      with advances in technology, expertise, and experience. To date, there has been
      no prospective study in the literature about the role of preoperative Double-J (D
      J) ureteral stenting in patients who undergo RPPL. This study is an endeavor to
      evaluate the role of preoperative D-J stenting in RPPL. METHODS: The study
      included 184 patients, who were randomized into 2 groups. Group A included 95
      patients, who underwent RPPL with D-J stenting. Group B included 89 patients, who
      underwent RPPL without D-J stenting. In group A, D-J stents were inserted under
      local anesthesia preoperatively, on the side of surgery. Complications during
      surgery and during the postoperative period were carefully recorded. RESULTS: The
      duration of drainage and volume in group A was significantly lower than in group
      B. The duration of postoperative stay was significantly reduced in group A (mean
      3.3 vs. 5.74 days). The analgesic requirement in group A also was significantly
      lower than in group B (mean 378.95 vs. 558.99 mg). No statistically significant
      difference existed between the two groups, in terms of minor intraoperative and
      postoperative complications (25.3% vs. 29.2%; p < or = 0.547). CONCLUSIONS: D-J
      stenting and type of renal pelvis influenced the results, i.e., duration of
      drainage, analgesic requirement, and duration of stay, in patients undergoing
      RPPL. However, there was no significant difference in operative time,
      intraoperative blood loss, and postoperative complications. D-J stent group had
      significant increase in the rate of urinary tract infection postoperatively.

PMID- 20044765
TI  - Is outpatient ERCP suitable, feasible, and safe? The experience of a Spanish
      community hospital.
AB  - BACKGROUND: We wanted to evaluate the safety of outpatient endoscopic retrograde
      cholangiopancreatography (ERCP). The follow-up of an ERCP outpatient during a
      short observation period could be a feasible and safe approach. METHODS: To
      evaluate the safety of outpatient ERCP, we assessed the rate of post-ERCP
      complications found and missed during a 6-h observation period after therapeutic
      ERCP. RESULTS: We performed 236 ERCPs on an outpatient basis, with a failure rate
      of 3.7% but with an overall completion rate for the intended treatment of 90.7%.
      Seventy-eight percent of the ERCPs were primarily therapeutic. The age of the
      patients was 63.9 years and 61.9% were females. One hundred seventy-seven (74.5%)
      patients were discharged from the hospital after the observation period. Thirty
      three (14.1%) patients were admitted without further delay due to unexpected ERCP
      findings or for early detection of complications. Twenty-seven (11.4%) patients
      had a prolonged hospital stay because of complications during the observation
      period. Just two patients previously discharged developed later complications:
      cholangitis and pancreatitis (0.84% of the ERCPs and 7.4% of the overall
      complications). There were 27 ERCP complications (12.1%). Of the overall
      complications, 29.6% were diagnosed very early after the procedure and 62.9% were
      diagnosed during the observation period. 8.9% out of the 12.1% of the ERCP
      complications were mild to moderate. There was no mortality. CONCLUSION: Twenty
      five (92.6%) of ERCP complications occurred during the first 6 h, making the use
      of this short observation period safe for an early discharge. The evolution of
      the patients who developed delayed complications was unremarkable. Whenever
      outpatient ERCP is feasible, it should be done to help cut costs.

PMID- 20044766
TI  - Single Port Access (SPA) laparoscopic ventral hernia repair: initial report of 30
      cases.
AB  - BACKGROUND: Laparoscopic ventral hernia repair has been demonstrated to be an
      acceptable and successful technique. Aside from similar, albeit fewer,
      complications compared to open hernia repair, the laparoscopic technique has the
      additional complication of port site hernia to its follow-up criteria. Our
      initial experience with reduced port surgery in hernias was described as a two
      port one-stitch repair technique in 2002. We initially applied our Single Port
      Access (SPA) technique to ventral hernia repairs and reported it at the American
      Hernia Society meeting in 2008. Now we present the first 30 cases, some with 6-24
      month follow-up. METHODS: The charts of 30 patients undergoing surgery for
      primary and recurrent ventral hernias employing the SPA technique were reviewed.
      The SPA technique was applied through a 1.0-1.6-cm incision remote from and
      lateral to the hernia location in the abdominal wall. Polypropylene-based coated
      mesh and non-fascial fixation were used in all cases. RESULTS: All procedures
      were completed via the SPA technique. Operative time, length of stay, and
      estimated blood loss were acceptable. The size of mesh placed ranged from 81 to
      500 cm(2). Postoperative seromas were observed and all resolved spontaneously.
      There have been no wound infections or port site hernias during the 6-24-month
      follow-up period. There have been no recurrent hernias at the primary site.
      CONCLUSION: We have successfully demonstrated the applicability of Single Port
      Access surgery for ventral hernia repair. In our initial series we performed this
      procedure on smaller hernias but have now begun applying it to larger repairs.

PMID- 20044767
TI  - Laparoscopic transcystic bile duct exploration: the treatment of first choice for
      common bile duct stones.
AB  - BACKGROUND: This study was designed to explore the role of transcystic bile duct
      exploration (TCE) as a first line of treatment for patients with suspected or
      incidental common bile duct (CBD) stones. METHODS: A prospective, case-control
      study of clinically comparable groups of patients who underwent laparoscopic
      cholecystectomy (LC) alone (n = 1,854) and combined LC/TCE for CBD stones (n =
      253) under the care of one surgeon was performed. Other than ultrasonography, no
      routine preoperative imaging was used; however, we performed routine
      intraoperative cholangiography on all patients. RESULTS: There was no difference
      in age (49 +/- 15 vs. 57 +/- 19, p = 0.7), sex (79% vs. 82% females, p = 0.6),
      and ASA grade (1.9 +/- 1 vs. 1.8 +/- 1, p = 0.7). A larger proportion of the TCE
      group presented as an emergency (TCE 45% vs. LC alone 27%, p = 0.03) and more
      often presented with acute biliary pain compared with LC alone (27% vs. 13%, p =
      0.02). Although a majority of the patients in the TCE group had clinical or
      biochemical risk factors for CBD stones (86%), only 27% had suspected stones on
      preoperative ultrasound. The incidence of jaundice (6% vs. 20%, p = 0.01) was
      lower in the LC alone group compared with TCE patients. Previous abdominal
      surgery was noted in 34% patients who underwent LC alone and 30% in LC/TCE (p =
      0.06). Significantly there was no difference in open conversion between the two
      groups (LC alone 0.5% vs. LC/TCE 0.6%, p = 0.07). Comparison of selected outcome
      parameters for LC versus TCE showed a postoperative hospital stay of 2 (1-14) vs.
      2 (1-17) days (p = 0.07), presentation to resolution 1 (1-11) vs. 1 (1-11) weeks
      (p = 0.07), and morbidity 1.07% vs. 1.2% (p = 0.07). CONCLUSIONS: The study
      advocates single-session laparoscopic cholecystectomy with transcystic CBD
      exploration as a feasible first choice treatment and the logical next step in the
      management of patients with CBD stones.

PMID- 20044768
TI  - Laparoscopic conversion of Roux-en-Y gastric bypass to biliopancreatic diversion.
AB  - BACKGROUND: This report describes the laparoscopic conversion of a Roux-en-Y
      gastric bypass (RYGBP) to biliopancreatic diversion (BPD). CASE REPORT: In
      January 1995, a 47-year-old woman with a body mass index (BMI) of 54 kg/m(2)
      benefited from a silicon ring vertical banded gastroplasty (SRVBG) for morbid
      obesity. She showed significant weight loss and reached a BMI of 30 kg/m(2).
      After 7 years, she experienced weight regain (BMI, 34.5 kg/m(2)), so a
      laparoscopic conversion to RYGBP was proposed. The patient again had a successful
      weight loss (BMI, 26 kg/m(2)), but 6 years later, she mentioned a weight regain
      (BMI, 33 kg/m(2)) with invalidating retrosternal pain. The nutritionist's
      analysis of the patient showed a certain modification of the alimentary character
      with frequent meals (grazing/polyphagia), and the psychologist's consultation
      identified an important binge-eating disorder. A laparoscopic conversion of RYGBP
      to BPD was proposed. The procedure consisted of (1) adhesiolysis and reduction of
      a hiatal hernia, (2) sectioning of the gastric pouch proximally to the
      gastrojejunostomy, (3) resection of the fundus of the gastric remnant excluded by
      the previous SRVBG, (4) restoration of the continuity of the stomach between the
      gastric pouch and the gastric remnant, (5) resection of the gastric antrum and
      pylorus, (6) deconstruction of the previous jejunojejunostomy, (7) restoration of
      the continuity of the small bowel, (8) measurement of the new common and
      alimentary limbs and construction of the jejunoileostomy, (9) closure of the
      mesenteric defect, (10) construction of the gastroileostomy, (11) closure of
      Petersen's space, and (12) repair of the hiatal hernia followed by a leak test.
      RESULTS: The operative time was 320 min, and the blood loss was 380 ml. The
      patient had an uneventful recovery and was discharged on postoperative day 5. Her
      BMI was 30.5 kg/m(2) after 3 months and 26 kg/m(2) after 6 months. The barium
      swallow showed good transit through the gastrointestinal tract. CONCLUSIONS: The
      laparoscopic conversion of RYGBP to BPD is technically feasible and effective
      during the short term for cases of repeated weight regain.

PMID- 20044769
TI  - Impact of established skills in open surgery on the proficiency gain process for
      laparoscopic surgery.
AB  - BACKGROUND: Laparoscopic training traditionally follows open surgical training.
      This study aimed to investigate the impact of experience in open surgery on the
      laparoscopic proficiency gain process. METHODS: A survey form investigating the
      importance of open experience before the start of laparoscopic training was sent
      to surgical experts and trainees in the United Kingdom. A separate experimental
      study objectively assessed the effects of open experience on laparoscopic skill
      acquisition using a virtual reality simulator. In the study, 11 medical students
      with no prior surgical experience (group A) and 14 surgical trainees with open
      but no laparoscopic experience in (group B) performed 250 simulated laparoscopic
      cholecystectomies. Psychomotor skills were evaluated by motion analysis and video
      based global rating scores. Before the first and after the fifth and tenth
      operation, knowledge of laparoscopic techniques was assessed by a written test
      and by self-reported confidence levels indicated on a questionnaire. RESULTS: The
      80 experts and 282 trainees who responded to the survey believed prior open
      experience aids confidence levels, knowledge, and skills acquisition. In the
      simulation study, no intergroup difference was found for any parameter after the
      first procedure. Group B scored significantly higher in the laparoscopic
      knowledge test before training began (42.7% vs. 64.3%; p = 0.002), but no
      significant difference was found after five operations. The two groups did not
      differ significantly in terms of confidence. Group B had a significantly shorter
      total operation time only at the first operation (2,305.6 s vs. 1,884.6 s; p =
      0.037). No significant intergroup difference in path length, number of movements,
      or video-based global rating scores was observed. CONCLUSIONS: Prior open
      experience does not aid the laparoscopic learning process, as demonstrated in a
      simulated setting. Given the wealth of evidence demonstrating translation of
      virtual skills to the operating theater, we propose that the safe and effective
      introduction of well-supervised laparoscopic training may be possible at the
      beginning of a surgical training curriculum.

PMID- 20044770
TI  - Open versus laparoscopic versus robotic gastrectomy for cancer: need for
      comparative-effectiveness quality.

PMID- 20044771
TI  - Outweighing the benefits and weakness of endoscopic submucosal dissection for
      early gastric cancer in the west.

PMID- 20044772
TI  - Laparoscopic surgery for inflammatory bowel disease: does weight matter?
AB  - BACKGROUND: Recent studies have shown improved outcomes after laparoscopic
      colorectal surgery compared with laparotomy for surgery for both benign and
      malignant colorectal diseases, including inflammatory bowel disease (IBD). This
      study was designed to evaluate the results of laparoscopic colorectal resections
      in normal weight patients compared with overweight and obese patients with IBD.
      METHODS: A retrospective analysis of a prospectively acquired institutional
      review board-approved surgical database was performed. All consecutive patients
      with IBD who underwent laparoscopy from January 1, 2000 to April 30, 2008 were
      reviewed. BMI, age, gender, comorbidities, ASA classification, and surgical- and
      disease-related variables, including 60-day postoperative complications, were
      reviewed. Chi-square, Mann-Whitney U test, and Student's t test were used for
      statistical analysis. RESULTS: A total of 261 patients with IBD underwent
      laparoscopy: 48 were excluded and 213 were analyzed. Group I comprised 127 normal
      weight patients (body mass index (BMI), 18.5-24.9 kg/m(2)), and group II included
      67 overweight patients (BMI, 25-29.9 kg/m(2)) and 19 obese patients (BMI >or= 30
      kg/m(2)). Crohn's disease was diagnosed in 86 (67.7%) patients in group I and 52
      (60.4%) in group II. Procedures performed included ileocolic resection in 56% of
      patients in each group. Total colectomy with or without proctectomy was
      undertaken in 39.4% in group I and 40.7% in group II. The conversion rate was 18%
      for group I and 22.09% for group II (p > 0.005; not significant). The most common
      reason for conversion was failure to progress due to adhesions or phlegmon. There
      were no differences in major postoperative complication rates (wound infection,
      abscess, anastomotic leakage, or small-bowel obstruction) or mean hospital stay
      (6.7, 6.8, respectively), and there was no mortality. CONCLUSIONS: Patients with
      IBD who were overweight or obese and who underwent laparoscopic bowel resection
      had no significant differences in the rates of conversion, major postoperative
      complications, or length of stay when comparing to patients with normal BMI.
      Therefore, the benefits of laparoscopic bowel resection should not be denied to
      overweight or obese patients based strictly on their BMI.

PMID- 20044773
TI  - Associated prothrombotic conditions are probably responsible for the occurrence
      of thrombosis in almost all patients with congenital FVII deficiency. Critical
      review of the literature.
AB  - The occasional occurrence of thrombosis in patients with congenital bleeding
      disorders has received considerable attention during the past decade. Myocardial
      infarction, ischemic strokes and venous thromboembolism have been reported in
      hemophilia A or B patients, in von Willebrand disease and, also, in rare
      coagulation disorders, especially in factor VII (FVII) deficiency. To explain the
      relatively high frequency of thrombotic phenomena, mainly venous, seen in the
      last condition, it was speculated that a special form or variant of FVII
      deficiency could exist. The presence of associated prothrombotic risk factors has
      been occasionally reported to be present in these patients but the matter has
      never been duly evaluated and emphasized. The purpose of the present paper was to
      evaluate if the clinical setting in which thrombosis appeared in these patients
      could explain the occurrence of the thrombosis. All reported cases of thrombosis
      seen in patients with FVII deficiency have been analyzed and the presence of
      associated risk factors recorded. Out of a population of 33 documented cases, the
      presence of prothrombotic risk factors was reported in 30 instances. In two of
      the remaining cases, no mention is made about associated risk factors. In the
      last case they were explicitly excluded. The critical evaluation of the
      literature suggests that the occurrence of thrombosis in FVII deficiency may be
      due to common prothrombotic risk factors. As a consequence it may be only stated
      that FVII deficiency does not protect from thrombosis.

PMID- 20044774
TI  - Bacterial adhesion onto materials with specific surface chemistries under flow
      conditions.
AB  - Staphylococcus epidermidis adhesion onto materials with specific chemical
      functionalities, under flow, was investigated by using surfaces prepared by self
      assembly of alkyl silane monolayers on glass. Terminal methyl (CH(3)) and amino
      (NH(2)) groups were formed by chemical vapor deposition of silanes, at elevated
      temperature. Carboxyl (COOH) terminated groups were prepared by further
      modification of NH(2) groups with succide anhydride and positively charged NH(2)
      groups by adsorption of poly-L: -lysine hydrobromide. Hydroxyl (OH) terminated
      glass was used as control. Surface modification was verified by contact angle
      measurements, atomic force microscopy and X-ray photoelectron spectroscopy. A
      parallel plate flow chamber was used to evaluate bacterial adhesion at various
      shear rates. Adhesion was found to be depended on the monolayer's terminal
      functionality. It was higher on the CH(3) followed by the positively charged
      NH(2), the non-charged NH(2) groups, the COOH and minimal on the OH-terminated
      glass. The increase in the material surface free energy significantly reduced the
      adhesion of a hydrophilic bacterial strain, and this is in accordance with the
      predictions of the thermodynamic theory. However, the increase in the shear rate
      restricted the predictability of the theory and revealed macromolecular
      interactions between bacteria and NH(2)- and COOH-terminated surfaces.

PMID- 20044775
TI  - Non-destructive evaluation of mechanical properties of poly (vinyl) alcohol
      hydroxyapatite nanocomposites.
AB  - Hydroxyapatite-poly (vinyl) alcohol nanocomposite powder was synthesized using
      varying poly (vinyl) alcohol concentrations. The dried powder was compacted into
      micro-porous disks at a load of 4 tons. The disks were sintered at 1200 degrees C
      to evolve porous nanocomposites. Size and shape of the pores observed in the
      scanning electron micrographs were quantified by using image processing software.
      Ultrasound velocity measurements were done to evaluate mechanical properties non
      destructively.

PMID- 20044777
TI  - Neuroprotective actions of the synthetic estrogen 17alpha-ethynylestradiol in the
      hippocampus.
AB  - 17alpha-ethynylestradiol (EE2), a major constituent of many oral contraceptives,
      is similar in structure to 17beta-estradiol, which has neuroprotective properties
      in several animal models. This study explored the potential neuroprotective
      actions of EE2 against kainic and quinolinic acid toxicity in the hippocampus of
      adult ovariectomized Wistar rats. A decrease in the number of Nissl-stained
      neurons and the induction of vimentin immunoreactivity in astrocytes was observed
      in the hilus of the dentate gyrus of the hippocampus after the administration of
      either kainic acid or quinolinic acid. EE2 prevented the neuronal loss and the
      induction of vimentin immunoreactivity induced by kainic acid at low (1
      microg/rat) and high (10-100 microg/rat) doses and exerted a protection against
      quinolinic acid toxicity at a low dose (1 microg/rat) only. These observations
      demonstrate that EE2 exerts neuroprotective actions against excitotoxic insults.
      This finding is relevant for the design of new neuroprotective estrogenic
      compounds.

PMID- 20044778
TI  - The G12 family proteins upregulate matrix metalloproteinase-2 via p53 leading to
      human breast cell invasion.
AB  - Although mounting evidence suggests a role for G(12) proteins, G(alpha12) and
      G(alpha13), in tumor progression, a direct role of G(12) proteins has not been
      determined. This study aims to elucidate the molecular mechanism for a
      tumorigenic and invasive potential of G(alpha12) and G(alpha13) in MCF10A human
      breast epithelial cells. Here, we report, for the first time, that G(alpha12) and
      G(alpha13) induce upregulation of matrix metalloproteinase (MMP)-2 leading to the
      invasive and migratory phenotypes in MCF10A cells. We further show that p53 is an
      important transcription factor for induction of MMP-2 transcriptional activation
      by G(alpha12/13). G(alpha12/13)-induced MMP-2 upregulation, invasion, and
      migration are dependent on the activation of Ras, Rac1, MKK3/6, p38, and Akt.
      Using human breast tissue samples, we demonstrate that the expression levels of
      G(alpha12) and MMP-2 are strongly correlated with the pathogenically diagnosed
      cancer (P < 0.0001). Moreover, the expression of G(alpha12) shows a strong
      correlation with that of MMP-2 in human breast cancer tissues, implicating the in
      vivo tumorigenic potential of G(alpha12). Taken together, this study elucidated
      the role of G(12) proteins in regulating processes for MMP-2 expression and
      malignant phenotypic conversion of MCF10A human breast epithelial cells,
      providing a molecular basis for the promoting role of G(alpha12) and G(alpha13)
      in breast cell invasion.

PMID- 20044779
TI  - Statin use in patients with chronic kidney disease stages 2-4: targeting beyond
      improved mortality rates.

PMID- 20044780
TI  - Revisiting the psychiatric day hospital experience 6 months after discharge: how
      was the transition and what have clients retained?
AB  - Psychiatric day hospitals offer intensive short-term multidisciplinary treatment.
      No study has examined in more depth the impact of this therapeutic experience in
      the life of participants and what they retained from their participation after
      discharge. A qualitative design using semi-structured individual interviews was
      completed with 18 participants of different gender, age and diagnosis, treated in
      a day hospital, 6 months after discharge. Interview themes addressed events and
      changes since discharge, learnings retained, appreciated components and
      suggestions. Results showed that the day hospital experience was particularly
      helpful to improve symptoms and relationship with self. It activated a self
      transformation process that continued afterwards. Termination created for many an
      abrupt void. Issues at stake during the first 6 months were continuity of care,
      social support and putting learnings into practice. The program offered at the
      day hospital was generally appreciated but management of the waiting time and
      linkage to outpatient services needed improvement.

PMID- 20044781
TI  - A PKC-beta inhibitor protects against cardiac microvascular ischemia reperfusion
      injury in diabetic rats.
AB  - PKC-beta inhibitor Ruboxistaurin (RBX or LY333531) can be used to reverse
      diabetic microvascular complication. However, it has not been previously
      established whether RBX can protect against ischemia/reperfusion (I/R) injury of
      cardiac microvessels in diabetic rats. STZ-induced diabetic rats were randomized
      into four groups and underwent I/R procedures. Cardiac barrier function and the
      region of cardiac microvascular lesion were examined. Cell monolayer barrier
      function was detected in cultured cardiac microvascular endothelial cells (CMECs)
      subjected to simulated I/R (SI/R). PKC-beta siRNA was transfected into CMECs to
      silence PKC-beta. Apoptosis Index of CMECs was detected by TUNEL assay and
      phosphor-LIMK2 protein expression was examined by Western blot analysis. RBX and
      insulin administration significantly reduced the cardiac microvascular lesion
      region and Apoptosis Index of endothelial cells (all P < 0.05 vs. no-treatment
      group). RBX decreased phosphor-LIMK2 expression (P < 0.05 vs. no-treatment
      group). RBX pretreatment and transfection with PKC-beta siRNA induced a rapid
      barrier enhancement in CMECs monolayer as detected by increased transendothelial
      electrical resistance (TER) and decreased FITC-dextran clearance (all P < 0.05
      vs. no-treatment group). Meanwhile, RBX pretreatment and transfection with PKC
      beta siRNA significantly decreased TUNEL positive CMECs and phosphor-LIMK2
      expression in cultured CMECs (all P < 0.05 vs. no-treatment group). RBX
      pretreatment reduced F-actin/G-actin in cultured CMECs, reproducing the same
      effect as PKC-beta siRNA. These data indicate that PKC-beta inhibitor (RBX) may
      be helpful in attenuating the risk of severe cardiac microvascular I/R injury in
      diabetic rats partly due to its maintenance of endothelial barrier function and
      anti-apoptotic effect.

PMID- 20044782
TI  - Impact of road traffic noise annoyance on health-related quality of life: results
      from a population-based study.
AB  - PURPOSE: To estimate the impact of traffic-related noise annoyance on health
      related quality of life (HrQoL) in a population-based study and potential effect
      modification by gender. METHODS: The study included 5,021 participants of the
      Swiss Cohort Study of Air Pollution and Lung Disease in Adults second survey. The
      association between traffic-related noise annoyance, measured on an 11-point
      scale, and HrQoL, based on SF-36 scores, was investigated by multivariate
      regression analysis. Effect sizes were calculated, and interactions by gender and
      chronic disease status examined. RESULTS: Thirteen percentage of the study
      population reported high annoyance due to traffic. Women were more likely to
      report high noise annoyance (adjOR 1.23; 95%CI 1.01-1.48). Except for general
      health, all SF-36 scores showed a significant negative association with noise
      annoyance. The respective effect sizes ranged between 0.13 and 0.54. Significant
      effect modification by gender and chronic disease status was present in specific
      SF-36 domains. CONCLUSION: This paper presents first evidence of an inverse
      relationship of noise annoyance and HrQoL in a general population. Although the
      estimated effects are small to moderate for individuals, they may add up to a
      relevant public health impact.

PMID- 20044783
TI  - Strong positive selection drives rapid diversification of R-genes in Arabidopsis
      relatives.
AB  - Although plant resistance (R) genes are extremely diverse and evolve rapidly,
      little is known about the mechanisms that generate this sequence divergence. To
      investigate these forces, we compared all nucleotide binding sites and leucine
      rich repeat R-genes between two closely related species, Arabidopsis thaliana and
      Arabidopsis lyrata. Our analyses revealed two distinct evolutionary patterns
      driven by either positive or stabilizing selection. Most R-genes (>50%) were
      evolving under strong positive selection characterized by high Ka/Ks ratios (>1),
      frequent recombination, copy number variation, and extremely high sequence
      divergence between the two species. The stably selected R-genes (<30%) have
      exactly the opposite four characters as the positively selected genes. The
      remaining R-genes (about 20%) are present in only one genome and absent from the
      other. A higher proportion of such genes were found to be part of TNL class
      (23.5%) compared to the non-TNL class (5.6%), suggesting different evolutionary
      patterns between these two groups. A significant correlation between Ka and
      divergence was revealed, indicating that the rapid evolution and diversification
      of R-genes were initiated by selectively generated, frequently shuffled and
      selectively maintained non-synonymous substitutions. Our genome-wide analyses
      confirmed an amazing mechanism by which plants to selectively accumulate and
      efficiently exploit these non-synonymous substitutions for their resistance to
      various pathogens.

PMID- 20044784
TI  - Systemic-onset juvenile idiopathic arthritis complicated by early onset
      amyloidosis in a patient carrying a mutation in the MEFV gene.
AB  - Systemic juvenile idiopathic arthritis (SJIA) is a disorder characterized by
      arthritis in children starting before 16 years of age associated with daily high
      fever, persisting for more than 2 weeks, and at least one of the following
      clinical features: evanescent cutaneous rash, lymphadenopathy, serositis or
      hepatosplenomegaly. SJIA patients carry a significantly higher frequency of MEFV
      mutations, the gene responsible for familial Mediterranean fever, and may be
      characterized by a more aggressive disease. In this line, we describe a 9-year
      old girl affected with SJIA who carried a heterozygous G196W mutation in MEFV.
      Our patient was characterized by an aggressive disease course, resistance to
      conventional immunosuppressive agents and developed renal amyloidosis just 2
      years after the disease onset.

PMID- 20044785
TI  - Treatment of inclusion body myositis: is low-dose intravenous immunoglobulin the
      solution?
AB  - Inclusion body myositis (IBM), the most common inflammatory myopathy in the
      elderly, is often resistant to various forms of therapy. Placebo-controlled
      treatment trials with high dose intravenous immunoglobulins (IVIG) have shown
      disease amelioration in some but not all patients. Here, we present the
      informative case of a 70-year-old woman with diagnosed inclusion body myositis
      that showed progressive muscle weakness without treatment and following immuno
      suppressive treatment with corticosteroids and azathioprine. A trial with low
      dose intravenous immunoglobulins was started at that time. The patient responded
      rapidly to low dose IVIG treatment with amelioration of muscle strength and
      normalization of CK serum activities. Our results demonstrate that IBM patients
      may respond to low-dose IVIG treatment which has important clinical and economic
      consequences.

PMID- 20044787
TI  - It is not hypoxia itself, but how you use it.

PMID- 20044786
TI  - Fructose and saturated fats predispose hyperinsulinemia in lean male rat
      offspring.
AB  - BACKGROUND: Early exposure to suboptimal nutrition during perinatal period
      imposes risk to metabolic disorders later in life. Fructose intake has been
      associated with increases in de novo lipogenesis, dyslipidemia, insulin
      resistance, and obesity. Excess consumption of saturated fat is associated with
      metabolic disorders. AIM OF THE STUDY: Objective of this animal study was to
      investigate morphological, metabolic, and endocrine phenotypes of male offspring
      born to dams consuming diets containing either 30% fructose, 9.9% coconut fat and
      0.5% cholesterol (F + SFA) or 30% glucose, and 11% corn oil (C), 1 month before
      conception and during gestation and nursing. METHODS: Proven male and female
      Sprague Dawley breeders were fed ad libitum with either F + SFA or C diet
      throughout the study. At weaning, five male pups from each group were sacrificed
      for determining morphological phenotypes. The other five male offspring from each
      group were rehabilitated to the C diet for an additional 12 weeks. At the age of
      15 weeks, morphological phenotypes and blood biochemistries [glucose, insulin,
      growth hormone (GH), insulin-like growth factor-1 (IGF-1), corticosterone, and
      testosterone] of male adult offspring were then assessed. RESULTS: Body weight
      (BW) and body length of the F + SFA male adult offspring was slightly smaller
      than the C. The BW-adjusted epididymal and retroperitoneal fat depots of the F +
      SFA adult offspring were significantly 18 and 44% smaller than the C,
      respectively. GH and IGF-1 were not different in adult offspring between groups.
      Fasted plasma insulin of the F + SFA adult offspring was 64% larger than the C (P
      <or= 0.0001) and homeostasis model assessment value was 55% larger (P = 0.004).
      There were negative correlations between fat depot sizes and plasma insulin in
      adult offspring. CONCLUSIONS: Our results suggest that, through fetal
      programming, an early exposure to both fructose and saturated fats may cause
      hyperinsulinemia and insulin insensitivity in the nonobese male rats later in
      life.

PMID- 20044789
TI  - Neonatal mortality risk for repeat cesarean compared to vaginal birth after
      cesarean (VBAC) deliveries in the United States, 1998-2002 birth cohorts.
AB  - To examine trends in repeat cesarean delivery, the characteristics of women who
      have repeat cesareans, and the risk of neonatal mortality for repeat cesarean
      birth compared to vaginal birth after cesarean (VBAC). Trends and characteristics
      of repeat cesareans were examined for: the period 1998-2002 for [1] all births,
      [2] low-risk births (singleton, term, vertex births) and [3] "no indicated risk"
      (NIR) births (singleton, term, vertex presentation births with no reported
      medical risks or complications). For low-risk and NIR births, neonatal mortality
      rates for repeat cesareans and VBACs were compared. Multivariate logistic
      regression was used to examine the risk of neonatal mortality for repeat
      cesareans and VBACs, after controlling for demographic and health factors. In
      2002 the repeat cesarean rate was 87.4%, and varied little by maternal risk
      status or by demographic and health characteristics. From 1998-2002 rates
      increased by 20% for low risk and by 21% for NIR births, respectively. For low
      risk women for the 1998-2002 birth cohorts, the adjusted odds ratio for neonatal
      mortality associated with repeat cesarean delivery (compared with VBAC) was 1.36
      (95% C.I. 1.20-1.55). For NIR women, the adjusted odds ratio was 1.24 (0.99
      1.55). The experience of a prior cesarean has apparently become a major
      indication for a repeat cesarean. Regardless of maternal risk status, almost 90%
      of women with a prior cesarean have a subsequent (i.e., repeat) cesarean
      delivery. This is the case even if there was no other reported medical
      indication. Our findings do not support the widely-held belief that neonatal
      mortality risk is significantly lower for repeat cesarean compared to VBAC
      delivery.

PMID- 20044790
TI  - Emerging viruses in the genus Comovirus.
AB  - The intraspecies variability of capsid proteins of five viruses of the genus
      Comovirus was established. Inclusion of both capsid proteins to the sequence
      analysis reduces some uncertainties about species/strains demarcation criteria in
      the Comovirus genus. New approach is proposed for discrimination of Turnip
      ringspot virus as a separate species.

PMID- 20044791
TI  - Detection of non-polio enteroviruses in Hungary 2000-2008 and molecular
      epidemiology of enterovirus 71, coxsackievirus A16, and echovirus 30.
AB  - Human enteroviruses are associated with various clinical syndromes from minor
      febrile illness to severe, potentially fatal conditions like aseptic meningitis,
      paralysis, myocarditis, and neonatal enteroviral sepsis. Between June 2000 and
      August 2008 echovirus (E) type 2, 4, 6, 7, 9, 11, 13, 25, 30, coxsackievirus (CV)
      -A16, -A19, -B5, and enterovirus 71 (EV71) were reported in Hungary. In this
      study, 29 previously enterovirus positive samples from 28 patients diagnosed with
      hand, foot and mouth disease, meningitis and encephalitis, were molecularly
      typed. The genetic relationships of identified serotypes CV-A16, EV71, and E30
      were assessed by direct sequencing of genomic region encoding the capsid protein
      VP1. The sequences were compared to each other and sequences from other
      geographical regions possessed in Genbank. The phylogenetic analysis of CV-A16
      revealed that the viruses were mostly of Far-Eastern or Asia-Pacific origin.
      Typing of EV71 showed that one virus from 2000 belonged to genotype C1 and five
      viruses observed in 2004 and 2005 were identified as genotype C4. The 11
      echovirus 30 strains showed homology with those of neighbor European countries.
      The molecular examination of E30 revealed that three separate lineages circulated
      in 2000, 2001, and 2004-2006 in Hungary.

PMID- 20044792
TI  - Development of real time PCR assays for detection and quantification of transgene
      DNA of a Bacillus thuringiensis (Bt) corn hybrid in soil samples.
AB  - Real time PCR assays were developed to detect and quantify the transgene DNA of a
      commercially released Bacillus thuringiensis (Bt) corn (Zea mays L.) hybrid
      (DKC42-23), which was derived from the event MON863 and also carried a neomycin
      phosphotransferase gene (the nptII gene). We applied the real time PCR assays to
      investigate the persistence of the transgene DNA in a field trial grown with
      DKC42-23 over 3 years, in combination with bacterial natural transformation. The
      results showed that under continuous cultivation of DKC42-23, its transgene DNA
      was detectable in the field plots all year around. Meanwhile, when soil DNA
      extracts from DKC42-23 plots were used as donor in bacterial natural
      transformation, successful recovery of kanamycin resistant (Km(R)) transformants
      indicated that the nptII gene carried by DKC42-23 could be taken up and
      integrated into naturally competent Pseudomonas stutzeri pMR7 cells, leading to
      the restoration of the antibiotic resistance of P. stutzeri pMR7. However, after
      the cultivation of a soybean line in the same plots for the subsequent growing
      season, the presence of transgene DNA of DKC42-23 was reduced to undetectable
      levels at the end of that growing season. Therefore, existing corn-soybean crop
      rotation practices reduce the availability of transgene DNA in soil and thus
      minimize the risks that might be attributable to horizontal gene transfer. The
      real time PCR assays are useful for investigating the persistence of transgene
      DNA derived from the MON863 event in soil environments.

PMID- 20044793
TI  - Retrospective versus prospective ECG-gated dual-source CT in pediatric patients
      with congenital heart diseases: comparison of image quality and radiation dose.
AB  - We wanted to compare the image quality and radiation dose of retrospective versus
      prospective ECG-gated dual-source CT imaging in pediatric patients with
      congenital heart diseases. We retrospectively evaluated 44 thorax CT images that
      were obtained using two different protocols (retrospective helical ECG-gated [n =
      22] versus prospective non-helical ECG-triggering [n = 22]) in patients younger
      than 5 years. Two radiologists evaluated the image quality, using a 3- or 4-point
      scale, in terms of the degree of homogeneity of vascular enhancement, the stair
      step artifacts, the subjective image noise and the overall subjective image
      quality. We compared the mean score of image quality, the frequency of marked
      stair-step artifact and the estimated radiation dose. The mean score of the
      homogeneity of vascular enhancement and the stair-step artifacts tended to be
      higher for the patients in the retrospective group than that for the patients in
      the prospective group, but this did not reach statistical significance. However,
      marked stair-step artifacts were significantly more frequent in the prospective
      scan group than that in the retrospective scan group (25.8 vs. 7.6%,
      respectively, P < 0.01). The mean scores for subjective image noise and the
      overall image quality were better in the retrospective group than those scores in
      the prospective group (P < 0.01). The mean estimated effective dose was higher
      for the retrospective ECG-gated helical scan than that for the prospective non
      helical scan (0.79 vs. 0.21 mSv, respectively, P < 0.01). Retrospective ECG-gated
      helical dual-source CT using aggressive ECG pulsing can be obtained with an
      acceptable radiation dose and superior image quality, as compared to the
      prospective ECG-triggering technique, for the evaluation of congenital heart
      diseases in pediatric patients who are younger than 5 years old.

PMID- 20044794
TI  - Gammarus spp. in aquatic ecotoxicology and water quality assessment: toward
      integrated multilevel tests.
AB  - The amphipod genus Gammarus is widespread and is structurally and functionally
      important in epigean freshwaters of the Northern Hemisphere. Its presence is
      crucial, because macroinvertebrate feeding is a major rate-limiting step in the
      processing of stream detrius. In addition, Gammarus interacts with multiple
      trophic levels bu functioning as prey, predator, herbivore, detritivore, and
      shredder. Such a broad span of ecosystem participation underlines the importance
      of Gammarus to pollutants and other disturbances may render it a valuable
      indicator for ecosystem health. This review summarizes the vast number of studies
      conducted with Gammarus spp. for evaluating aquatic ecotoxicology endpoints and
      examines the suitability of this native invertabrate species for the assessment
      of stream ecosystem health in the Northern Hemisphere. Numerous papers have been
      published on how pollutants affect gammarind behavior (i.e., mating, predator
      avoidance), reproduction, development, feeding activity, population structure, as
      well as the consequences of pollution on host-parasite, predator-prey, or native
      invasive species interactions. Some biochemical and molecular biomarkers have
      already been established, such as the measurement of vitellogenin-like proteins,
      metallothioneins, alkali-labile phosphates (in proteins), and lipogenic enzyme
      activities for assessing endocrine distribution and detoxification mechanisms.

PMID- 20044795
TI  - The Svalbard glaucous gull as bioindicator species in the European arctic:
      insight from 35 years of contaminants research.
AB  - Biomonitoring survey conducted with glaucous gulls from Svalbard have
      demonstrated that this top-predator-scavenger species accumulates a wide array of
      chemicals of environmental concern, including organohalogens, trace elements,
      organometals, and several non-halogenated and non-metallic-compounds. Among these
      contaminants are those subjected to global bans or restrictions in North America
      and Europe (e.g., legacy OC's, penta-, and octa-PBDE technical mixtures and
      mercury). In addition, some currently produced chemicals were found in gulls that
      lack and global use regulation (e.g., deca-PBDE , HBCD, and other non-PBDE BFR
      additives, siloxanes, and selected PFASs). Svalbard glaucous gulls are also
      exposed to contaminant metabolites that, at time, are more bioactive than their
      precursors (e.g., oxychlordane, p,p'-DDE, OH- and MeSo2-PCBs, and OH-PBDEs)
      Concentrations of legacy OCs (PCBs, DDTs, CHLs, CBzs, dieldrin, PCDD/Fs, and
      mirec) in tissues, blood, and eggs of Svalbard glaucous gulls have displayed the
      highest contamination levels among glaucous gull populations that inhabit
      Greenland (Cleemann et al. 2000) Jan Mayen (Gabrielsen et al. 1997), Alaska
      (Vander Pol et al. 2009), and the Canadian Arctic (Braune et a. 2005). To date,
      measurements obtaines on more novel organohalogens (e.g., OH- and MeSo2
      containing metabolites, BFRs and PFASs) in Svalbard glaucous gull samples
      generally confirm that the spatial and trophodynamic trends of the legacy OC
      concentrations, whereas no clear trend emerges from surveys of trace elements and
      organometals. Using the glaucous gull as biosentinel species provides clear
      evidence that Svalbard and the European Arctic environment is exposed to a
      complex mixture of legacy and more recently introduced PBT-like substances.

PMID- 20044796
TI  - Fenamiphos and related organophosphorus pesticides: environmental fate and
      toxicology.
AB  - In this review, we emphasize recent research on the fate, transport, and
      metabolism of tree selected organophosphorus pesticides (fenamiphos, isofenphos,
      and coumaphos) in soil an water environments. This review is also concerned with
      the side effects of these pesticides on nontarget organisms. Despite the fact
      that fenamiphos is not very mobile, its oxides have been detected in the
      groundwaters of Western Australia. Most organophosphorus pesticides generally are
      chemically unstable and underfo microbial degradation in soil and water
      environments. Enhanced biodegradation of many organophosphorus pesticides upon
      their repeted applications to soil and water is well established. Myriads of soil
      microorganisms, bacteria in particular, exhibit an exceptional capacity to
      transform many organophosphorus pesticides. Fenamiphos can undergo rapid
      microbially mediated degradation via oxidation to its oxides (sulfoxide and
      sulfone) and eventually to CO2 and water in soils, or via hydrolysis, in cultures
      of the soil bacterium, Brevinbacterium sp. There is evidence for enhanced
      biodegradation of (i) isofenphos in soils with a long history of use and (ii)
      coumaphos in cattle dip by bacterial cultures to chlorferon and
      diethylthiophosphoric acid.

PMID- 20044797
TI  - Isolated spontaneous renal artery dissection: diagnosis and endovascular
      management.
AB  - Spontaneous, isolated focal renal artery dissection is an extremely rare cause of
      renovascular hypertension. Imaging technology for the renal arteries has evolved
      recently with the development of multidetector computed tomography angiography
      (CTA), and intravascular ultrasound. We describe a 52-year-old man with
      spontaneous renal artery dissection complicated by renovascular hypertension,
      successfully diagnosed initially with CTA, then evaluated by intravascular
      ultrasound, and finally, treated successfully with stenting.

PMID- 20044798
TI  - Percutaneous aspiration thrombectomy in the treatment of lower extremity
      thromboembolic occlusions.
AB  - PURPOSE: To report the immediate and midterm results of manual aspiration
      thrombectomy as the first thrombus removal method in the treatment of acute or
      early chronic arterial thromboembolism in the lower extremity. MATERIALS AND
      METHODS: Retrospective review of 40 limbs in 37 nonconsecutive patients between
      March 2006 and March 2008 (21 female [57%], 16 male; mean age, 67 +/- 10 years;
      age range, 42-84 years) who had percutaneous aspiration thrombectomy for lower
      limb arterial thromboembolism. Twenty-nine legs had acute ( < 14 days) and 11
      legs had early chronic (15-60 days) thromboembolism. Clinical categories of limb
      ischemia were stage I in 12 limbs, stage IIa in 17 limbs, and stage IIb in 11
      limbs. RESULTS: Technical success was achieved in 35 limbs (88%). Complete
      thrombus removal was achieved in 26 of 29 limbs (90%) with acute occlusions and 4
      of 11 limbs (36%) with early chronic occlusions (P < 0.05, chi(2) test).
      Amputation-free survival rate was 100% at one month, 93% at one year, and 93% at
      two years with Kaplan-Meier survival analysis. Freedom from symptoms of
      claudication or critical limb ischemia was achieved in 31 of 39 limbs (80%) at
      one month and 25 of 35 limbs (71%) at one year. There were three major
      complications and ten minor complications. CONCLUSION: Percutaneous aspiration
      thrombectomy is a rapid and effective way of removing thrombus in thromboembolic
      occlusions of the limb arteries below the inguinal ligament. It can be used in
      patients with acute limb ischemia (Rutherford clinical category IIb).

PMID- 20044799
TI  - MVPACK: a package to calculate energy levels and magnetic properties of high
      nuclearity mixed valence clusters.
AB  - We present a FORTRAN code based on a new powerful and efficient computational
      approach to solve the double exchange problem for high-nuclearity MV clusters
      containing arbitrary number of localized spins and itinerant electrons. We also
      report some examples in order to show the possibilities of the program.

PMID- 20044800
TI  - The methanolic extract of Withania somnifera ACTS on GABAA receptors in
      gonadotropin releasing hormone (GnRH) neurons in mice.
AB  - The effect of the methanol extract of Withania somnifera (mWS) on the
      gonadotropin releasing hormone (GnRH) neuron was examined in juvenile mice using
      the whole cell patch clamp technique. GnRH neurons are the fundamental regulators
      of the pulsatile release of GnRH needed for puberty and fertility. GnRH neurons
      were depolarized by bath application of the mWS (400 ng/microl) under the
      condition of a high Cl(-) pipette solution in current clamp mode. In voltage
      clamp mode, mWS induced reproducible inward currents (31.7 +/- 5.51 pA, n = 14).
      The mWS-induced inward currents persisted in the presence of tetrodotoxin (TTX,
      0.5 microM), but were suppressed by bicuculline methiodide (BMI, 20 microM), a
      GABA(A) receptor antagonist. These results show that mWS affects the neuronal
      activities by mediating the GABA(A) receptor, which suggests that WS contains an
      ingredient with possible GABAmimetic activity.

PMID- 20044801
TI  - The biological, clinical and prognostic implications of p53 transcriptional
      pathways in breast cancers.
AB  - We hypothesized that the functional status of p53 transcriptional pathways,
      rather than p53 protein expression alone, could accurately discriminate between
      low- and high-risk breast carcinoma (BC) and inform about individuals' tumour
      biological behaviour. To test this, we studied a well-characterized series of 990
      BCs with long-term follow-up, immunohistochemically profiled for p53, its main
      regulators and downstream genes. Results were validated in an independent series
      of patients (n = 245) uniformly treated with adjuvant anthracycline-based
      chemotherapy. Eleven p53 transcriptional phenotypes were identified with just two
      main clinical outcomes. (a) Low risk/good prognosis group (active/partially
      inactive p53 pathways), defined as p53(+/-)/MDM4(+)/MDM2(+/-)/Bcl2(+/-)/p21(+/-),
      p53(-)/MDM4(-)/MDM2(+)/Bcl2(+)/p21(+/-) and p53(+/-)/MDM4(-)/MMD2(
      )/Bcl2(+)/p21(+/-). These tumours had favourable clinicopathological
      characteristics, including ER(+) and long survival after systemic adjuvant
      therapy (AT). (b) High risk/poor prognosis group (completely inactive p53
      pathways), defined as p53(+/-)/MDM4(-) MDM2(-)/Bcl2(-)/p21(-), p53(-)/MDM4(-)
      MDM2(+)/Bcl2(-)/p21(-) and p53(+/-)/MDM4(-)/MDM2(-)/Bcl2(-)/p21(+). These tumours
      were characterized by aggressive clinicopathological characteristics and showed
      shortened survival when treated with AT. Completely inactive p53 pathways but
      intact p21 axis p53(+/-)/MDM4(-)/MDM2(-)/Bcl2(-)/p21(+) had the worst prognosis,
      particularly patients who received AT. Multivariate Cox regression models,
      including validated prognostic factors for both test and validation series,
      revealed that the functional status of p53 transcriptional pathways was an
      independent prognosticator for BC-specific survival (HR 2.64 and 4.5, p < 0.001,
      respectively) and disease-free survival (HR 1.93 and 2.5, p < 0.001,
      respectively). In conclusion, p53 functional status determined by assessment of
      p53 regulatory and downstream targets provides independent prognostic value and
      may help determine more adequate therapeutic regimens for specific subgroups of
      breast cancer patients.

PMID- 20044802
TI  - p53 transcriptional pathways in breast cancer: the good, the bad and the complex.
AB  - A p53 network immunohistochemically-based signature to discriminate between good
      and poor prognosis breast cancer would have clinical relevance, given the key
      role of p53 in malignancy and response to therapy. Utilizing a five-protein
      signature of p53/mdm2/mdm4/bcl2/p21 discriminates good-prognosis and poor
      prognosis patient groups, based on the functionality of the p53 network. However,
      the relationship of this five-protein signature to p53 mutation, the wide range
      of breast cancer therapies now in use and the over-70 age group remain uncertain.
      Nonetheless, confirmation of the signature in two independent series suggests
      that this approach should be considered in further case series and in the context
      of clinical trials.

PMID- 20044803
TI  - Down-regulation of the LXR transcriptome provides the requisite cholesterol
      levels to proliferating hepatocytes.
AB  - Cholesterol homeostasis is critical for cellular proliferation. Liver X receptor
      (LXR) alpha and beta are the nuclear receptors responsible for regulation of
      cholesterol metabolism. In physiological conditions, high intracellular
      cholesterol levels cause increased synthesis of oxysterols, which activate LXR,
      thus triggering a transcriptional response for cholesterol secretion and
      catabolism. Here we employed a mouse model of partial hepatectomy (PH) to dissect
      the molecular pathways connecting cholesterol homeostasis, cellular
      proliferation, and LXR. First, we show that hepatic cholesterol content increases
      after PH, whereas the entire LXR transcriptome is down-regulated. Although LXR
      messenger RNA (mRNA) levels are unmodified, LXR target genes are significantly
      down-regulated on day 1 after PH and restored to control levels on day 7, when
      the liver reaches normal size. The inactivation of LXR following PH is related to
      the reduced oxysterol availability by way of decreased synthesis, and increased
      sulfation and secretion. On the contrary, cholesterol synthesis is up-regulated,
      and extracellular matrix remodeling is enhanced. Second, we show that
      reactivation of LXR by way of a synthetic ligand determines a negative modulation
      of hepatocyte proliferation. This effect is sustained by the reactivation of
      hepatic cholesterol catabolic and secretory pathways, coupled with a significant
      reduction of cholesterol biosynthesis. Our data unveil a previously unrecognized
      and apparently paradoxical scenario of LXR modulation. During liver regeneration
      LXR activity is abated in spite of increasing intracellular cholesterol levels.
      Turning off LXR-transcriptional pathways is crucial to guaranteeing the requisite
      intracellular cholesterol levels of regenerating hepatocytes. In line with this
      hypothesis, pharmacological LXR reactivation during PH significantly reduces
      liver regeneration capacity.

PMID- 20044804
TI  - Mitogen-inducible gene-6 is a negative regulator of epidermal growth factor
      receptor signaling in hepatocytes and human hepatocellular carcinoma.
AB  - The mitogen-inducible gene-6 (mig-6) is a multi-adaptor protein implicated in the
      regulation of the HER family of receptor tyrosine kinases. We have reported
      recently that mig-6 is a negative regulator of epidermal growth factor receptor
      (EGFR)-dependent skin morphogenesis and tumor formation in vivo. In the liver,
      ablation of mig-6 leads to an increase in EGFR protein levels, suggesting that
      mig-6 is a negative regulator of EGFR function. In line with this observation,
      primary hepatocytes isolated from mig-6 knockout and wild-type control mice
      display sustained mitogenic signaling in response to EGF. In order to explore the
      role of mig-6 in the liver in vivo, we analyzed liver regeneration in mig-6
      knockout and wild-type control mice. Interestingly, mig-6 knockout mice display
      enhanced hepatocyte proliferation in the initial phases after partial
      hepatectomy. This phenotype correlates with activation of endogenous EGFR
      signaling, predominantly through the protein kinase B pathway. In addition, mig-6
      is an endogenous inhibitor of EGFR signaling and EGF-induced tumor cell migration
      in human liver cancer cell lines. Moreover, mig-6 is down-regulated in human
      hepatocellular carcinoma and this correlates with increased EGFR expression.
      CONCLUSION: Our data implicate mig-6 as a regulator of EGFR activity in
      hepatocytes and as a suppressor of EGFR signaling in human liver cancer.

PMID- 20044805
TI  - Cleavage of mitochondrial antiviral signaling protein in the liver of patients
      with chronic hepatitis C correlates with a reduced activation of the endogenous
      interferon system.
AB  - Hepatitis C virus (HCV) infection induces the endogenous interferon (IFN) system
      in the liver in some but not all patients with chronic hepatitis C (CHC).
      Patients with a pre-activated IFN system are less likely to respond to the
      current standard therapy with pegylated IFN-alpha. Mitochondrial antiviral
      signaling protein (MAVS) is an important adaptor molecule in a signal
      transduction pathway that senses viral infections and transcriptionally activates
      IFN-beta. The HCV NS3-4A protease can cleave and thereby inactivate MAVS in
      vitro, and, therefore, might be crucial in determining the activation status of
      the IFN system in the liver of infected patients. We analyzed liver biopsies from
      129 patients with CHC to investigate whether MAVS is cleaved in vivo and whether
      cleavage prevents the induction of the endogenous IFN system. Cleavage of MAVS
      was detected in 62 of the 129 samples (48%) and was more extensive in patients
      with a high HCV viral load. MAVS was cleaved by all HCV genotypes (GTs), but more
      efficiently by GTs 2 and 3 than by GTs 1 and 4. The IFN-induced Janus kinase
      (Jak)-signal transducer and activator of transcription protein (STAT) pathway was
      less frequently activated in patients with cleaved MAVS, and there was a
      significant inverse correlation between cleavage of MAVS and the expression level
      of the IFN-stimulated genes IFI44L, Viperin, IFI27, USP18, and STAT1. We conclude
      that the pre-activation status of the endogenous IFN system in the liver of
      patients with CHC is in part regulated by cleavage of MAVS.

PMID- 20044806
TI  - Efficacy of entecavir in chronic hepatitis B patients with mildly elevated
      alanine aminotransferase and biopsy-proven histological damage.
AB  - Current guidelines for management of chronic hepatitis B recommend treatment for
      patients presenting with elevated hepatitis B virus (HBV) DNA and alanine
      aminotransferase (ALT) >2 x upper limit of normal (ULN) or histological evidence
      of liver disease. Retrospective analyses have demonstrated that significant
      hepatic necroinflammation and fibrosis were present in a substantial proportion
      of patients with ALT 1 to 2 x ULN. To assess therapeutic efficacy in this
      clinical setting, we retrospectively examined treatment endpoints among the
      subset of nucleoside-naive chronic hepatitis B (CHB) patients treated in phase 3
      clinical trials of entecavir who had both screening and baseline serum ALT 1.3 to
      2 x ULN. A total of 1347 patients were randomized to treatment with entecavir or
      lamivudine. Three hundred thirty-six patients, constituting 25% of the total
      study population, had screening and baseline ALT 1.3 to 2 x ULN. Clinically
      significant necroinflammation (Knodell necroinflammation score > or =7) was
      observed in 60% and 72% of hepatitis B e antigen (HBeAg)-positive and HBeAg
      negative patients, respectively, whereas marked fibrosis (Ishak fibrosis score >
      or =4) was observed in 8% and 15% of HBeAg-positive and HBeAg-negative patients,
      respectively. Among entecavir-treated HBeAg-negative patients, the proportions of
      patients achieving histological improvement, HBV DNA <300 copies/mL, and ALT
      normalization were similar between patients with mildly elevated ALT and those
      with ALT >2 x ULN. However, entecavir-treated HBeAg-positive patients with mildly
      elevated ALT had lower response rates for histological improvement, HBV DNA less
      than 300 copies/mL, ALT normalization, and HBeAg seroconversion than those with
      ALT greater than 2 x ULN. CONCLUSION: This retrospective analysis demonstrated
      that HBeAg-negative CHB patients treated with entecavir responded similarly
      irrespective of baseline ALT level. However, HBeAg-positive patients with mildly
      elevated ALT responded less well to treatment with entecavir than did those with
      ALT greater than 2 x ULN.

PMID- 20044807
TI  - Reduction of advanced liver fibrosis by short-term targeted delivery of an
      angiotensin receptor blocker to hepatic stellate cells in rats.
AB  - There is no effective therapy for advanced liver fibrosis. Angiotensin type 1
      (AT1) receptor blockers attenuate liver fibrogenesis, yet their efficacy in
      reversing advanced fibrosis is unknown. We investigated whether the specific
      delivery of an AT1 receptor blocker to activated hepatic stellate cells (HSCs)
      reduces established liver fibrosis. We used a platinum-based linker to develop a
      conjugate of the AT1 receptor blocker losartan and the HSC-selective drug carrier
      mannose-6-phosphate modified human serum albumin (losartan-M6PHSA). An average of
      seven losartan molecules were successfully coupled to M6PHSA. Rats with advanced
      liver fibrosis due to prolonged bile duct ligation or carbon tetrachloride
      administration were treated with daily doses of saline, losartan-M6PHSA, M6PHSA
      or oral losartan during 3 days. Computer-based morphometric quantification of
      inflammatory cells (CD43), myofibroblasts (smooth muscle alpha-actin [alpha-SMA])
      and collagen deposition (Sirius red and hydroxyproline content) were measured.
      Hepatic expression of procollagen alpha2(I) and genes involved in fibrogenesis
      was assessed by quantitative polymerase chain reaction. Losartan-M6PHSA
      accumulated in the fibrotic livers and colocalized with HSCs, as assessed by
      immunostaining of anti-HSA and anti-alpha-SMA. Losartan-M6PHSA, but not oral
      losartan, reduced collagen deposition, accumulation of myofibroblasts,
      inflammation and procollagen alpha2(I) gene expression. Losartan-M6PHSA did not
      affect metalloproteinase type 2 and 9 activity and did not cause apoptosis of
      activated HSCs. CONCLUSION: Short-term treatment with HSC-targeted losartan
      markedly reduces advanced liver fibrosis. This approach may provide a novel means
      to treat chronic liver diseases.

PMID- 20044808
TI  - Adenosine inhibits chemotaxis and induces hepatocyte-specific genes in bone
      marrow mesenchymal stem cells.
AB  - Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic potential in
      liver injury, but the signals responsible for MSC localization to sites of injury
      and initiation of differentiation are not known. Adenosine concentration is
      increased at sites of cellular injury and inflammation, and adenosine is known to
      signal a variety of cellular changes. We hypothesized that local elevations in
      the concentration of adenosine at sites of tissue injury regulate MSC homing and
      differentiation. Here we demonstrate that adenosine does not induce MSC
      chemotaxis but dramatically inhibits MSC chemotaxis in response to the
      chemoattractant hepatocyte growth factor (HGF). Inhibition of HGF-induced
      chemotaxis by adenosine requires the A2a receptor and is mediated via up
      regulation of the cyclic adenosine monophosphate (AMP)/protein kinase A pathway.
      This results in inhibition of cytosolic calcium signaling and down-regulation of
      HGF-induced Rac1. Because of the important role of Rac1 in the formation of actin
      stress fibers, we examined the effect of adenosine on stress fiber formation and
      found that adenosine inhibits HGF-induced stress fiber formation. In addition, we
      found that adenosine induces the expression of some key endodermal and hepatocyte
      specific genes in mouse and human MSCs in vitro. CONCLUSION: We propose that the
      inhibition of MSC chemotaxis at sites of high adenosine concentration results in
      localization of MSCs to areas of cellular injury and death in the liver. We
      speculate that adenosine might initiate the process of differentiation of MSCs
      into hepatocyte-like cells.

PMID- 20044809
TI  - The heme oxygenase 1 product biliverdin interferes with hepatitis C virus
      replication by increasing antiviral interferon response.
AB  - The anti-inflammatory and antiapoptotic heme degrading enzyme heme oxygenase-1
      (HO-1) has been shown recently to interfere with replication of hepatitis C virus
      (HCV). We investigated the effect of HO-1 products carbon monoxide (CO), iron and
      biliverdin on HCV replication using the replicon cell lines Huh-5-15 and
      LucUbiNeo-ET, stably expressing HCV proteins NS3 through NS5B. Incubation of
      these cell lines in the presence of the CO donor methylene chloride transiently
      reduced HCV replication, whereas an increase of iron in cell culture by
      administration of FeCl(3) or iron-saturated lactoferrin did not interfere with
      HCV replication. Likewise, depletion of iron by deferoxamine during induction of
      HO-1 by cobalt-protoporphyrin IX did not restore HCV replication. The most
      prominent effect was observed after incubation of replicon cell lines in the
      presence of biliverdin. Biliverdin seems to interfere with HCV replication
      mediated oxidative stress by inducing expression of antiviral interferons, such
      as interferon alpha2 and alpha17. CONCLUSION: The antioxidant biliverdin reduces
      HCV replication in vitro by triggering the antiviral interferon response and
      might improve HCV therapy in the future.

PMID- 20044810
TI  - The predictors of the presence of varices in patients with primary sclerosing
      cholangitis.
AB  - The predictors for developing varices in patients with primary sclerosing
      cholangitis (PSC) have not been well studied prospectively. We sought to define
      the predictors for the presence of varices at baseline and for newly developing
      varices in patients with PSC. We used prospectively collected data from a
      multicenter randomized trial of high dose ursodeoxycholic acid for PSC. All 150
      patients enrolled were reviewed for predictors of varices and we excluded 26
      patients who had esophageal varices at baseline so that predictors of newly
      developing varices could be determined. Clinical examination, blood tests, and
      upper endoscopy were done before randomization, at 2 years and after 5 years.
      Liver biopsy was performed at entry and at 5 years. The median age (interquartile
      range) of patients was 45.9 years (35.8, 54.9). In a multivariable logistic
      regression, a higher Mayo risk score (> or =0.87) or a higher aspartate/alanine
      aminotransferase (AST/ALT) ratio (> or =1.12) were significantly associated with
      the presence of varices at initial endoscopy (odds ratio = 1.9 and 3.9). By the
      end of the study, 25 patients had new varices (20.2%). In a Cox model, after
      adjustment for baseline variables lower platelet count and higher total bilirubin
      at 2 years were significantly associated with the presence of new varices. The
      platelet count of 205 (x 10(9)/L) and the total bilirubin level of 1.7 mg/dL were
      the best cutoff values for the detection of new varices. CONCLUSION: A higher
      Mayo risk score and higher AST/ALT ratio were significantly associated with the
      presence of varices at initial endoscopy. Lower platelet count and higher total
      bilirubin at 2 years were significantly associated with an increased risk of
      developing new varices in patients with PSC.

PMID- 20044812
TI  - [Thought between the studies on the course of schizophrenia].

PMID- 20044813
TI  - [Transfer of psychiatric care to the community level and the related local
      support: a view from psychiatric hospitals. A thought on the community
      corporation that is needed at the present].

PMID- 20044811
TI  - The tbx/bHLH transcription factor mga regulates gata4 and organogenesis.
AB  - The mga gene encodes a unique transcription factor containing both TBOX and
      bHLHzip DNA-binding domains. Here we describe the structure, expression pattern,
      and loss-of-function phenotype for zebrafish mga. The mga gene is conserved with
      mammalian homologs for both DNA-binding domains. It is expressed maternally, and
      subsequently in the developing brain, heart, and gut, and its depletion causes
      morphogenetic defects in each of these organ systems. The heart and gut
      phenotypes are similar to those described previously for loss of gata4, and the
      mga morphant shows increased levels of gata4 transcripts in lateral mesoderm.
      Knockdown of gata4 rescues the early heart-looping defect (but not the gut
      defect), indicating that mga restricts the normal levels of Gata4 required for
      heart tube looping, while both genes are important for gut development.
      Transcript profiling experiments show that mga functions early to influence key
      regulators of mesendoderm, including tbx6, cas, and sox17.

PMID- 20044814
TI  - [The era of the transfer of patient care to the community as a radical transition
      and the attitude of psychiatrists].

PMID- 20044815
TI  - [Survey on employment of psychiatric patients on day care and an NPO network for
      the support of occupational rehabilitation of psychiatric patients in Osaka
      (JSN)].

PMID- 20044816
TI  - [On the support for the employment of psychiatric patients].

PMID- 20044818
TI  - [Support of psychiatric patients with occupational rehabilitation: additional
      presentation].

PMID- 20044817
TI  - [Support for occupational rehabilitation extended by psychiatric clinics].

PMID- 20044819
TI  - [The present status and future of the law concerning medical observation of the
      mentally disturbed who committed crime].

PMID- 20044820
TI  - [Does the law concerning observation of the criminally insane contribute to the
      improvement of psychiatric care?].

PMID- 20044821
TI  - [Significance and the role of re-examination of the law concerning medical
      observation of the criminally insane].

PMID- 20044822
TI  - [Now is the time to abolish the law concerning medical observation of medically
      insane and drastically revise the psychiatric care].

PMID- 20044823
TI  - [Practice of psychiatric emergency at prefectural general hospitals].

PMID- 20044824
TI  - [The effect of the financial gain from psychiatric emergencies and
      hospitalization due to their complications on the management of the psychiatric
      department of a general hospital].

PMID- 20044825
TI  - [Requests by hospitals specializing in psychiatric care (facilities with
      permission to charge for emergency admission to psychiatric departments) to
      psychiatric departments of general hospitals--based on the conditions of the
      patients hospitalized with somatic complications in a 3-year period].

PMID- 20044826
TI  - [Expectations for creating psychiatric wards at general hospitals: a viewpoint
      from medical management].

PMID- 20044827
TI  - [Cognition disorders involving schizophrenic patients: current topics].

PMID- 20044828
TI  - [Basis of progressive changes in schizophrenia--abnormalities in the substantia
      alba and dynamics of oligodendrocytes].

PMID- 20044829
TI  - [Clinical significance of imaging of the brain structure in schizophrenia].

PMID- 20044830
TI  - [Understanding of the actual state and optimization of psychiatric care to hasten
      hospital discharge].

PMID- 20044831
TI  - Proteomic screening for possible effector molecules secreted by the obligate
      intracellular pathogen Coxiella burnetii.
AB  - Coxiella burnetii is a Gram-negative, gamma-proteobacteria with nearly worldwide
      distribution, and it is the pathogenic agent of Q-fever in man. It is an obligate
      intracellular parasite that is highly adapted to reside within the eukaryotic
      phagolysosome. In fact, it is the only known intracellular bacterium that manages
      to survive and replicate within a fully formed, acidic phagolysosome. C. burnetti
      possesses a functional Type 4 Secretion System (T4SS), similar to the Dot/Icm
      system of Legionella pneumophila. Up to date there have been no reports for the
      effector molecules secreted by Coxiella's T4SS. These are speculated to have
      quite different roles than the effectors of other intracellular pathogens, since
      there is no need for phagosomal arrest or escape in the case of Coxiella. In this
      study, we have investigated the cytoplasm of Vero cells infected with C. burnetti
      strain Nine Mile Phase II. We have identified by mass spectrometry (ESI-MS/MS)
      several C. burnetti proteins that bear typical characteristics of effector
      molecules. Most of the identified proteins were also very alkaline, something
      which is supportive for a protective strategy that has evolved in this bizarre
      pathogen against acidic environments.

PMID- 20044832
TI  - Combined NMR and LC-MS analysis reveals the metabonomic changes in Salvia
      miltiorrhiza Bunge induced by water depletion.
AB  - Plant metabonomic analysis is essential for understanding plant systems responses
      to osmotic stresses. To understand the comprehensive metabolic responses of
      Salvia miltiorrhiza Bunge (SMB) to continuous and exhaustive water depletion, we
      characterized the SMB metabonomic variations induced by three different drying
      processes using the combined NMR and LC-DAD-MS method. NMR results showed that
      SMB extracts were dominated by 29 primary metabolites such as sugars, carboxylic
      acids and amino acids, which were comprehensively reported for the first time,
      and 8 secondary metabolites including polyphenolic acids and diterpenoids. LC-DAD
      MS methods detected 44 secondary metabolites, among which 5 polyphenolic acids
      together with genipin, umbelliferone and tormentic acid were found for the first
      time in this plant. We found that aqueous methanol was efficient in extracting
      both primary metabolites and polyphenolic acids, whereas chloroform-methanol was
      effective in selectively extracting diterpenoids. We further found that air- and
      sun-drying markedly affected both primary and secondary metabolisms of SMB by
      enhancing tanshinone and glutamate-mediated proline biosynthesis and altering
      carbohydrate and amino acid metabolisms. The shikimate-mediated biosynthesis of
      polyphenolic acids was promoted by air-drying but suppressed by sun-drying. These
      findings fill the gap of our understandings to the metabolic responses of S.
      miltiorrhiza Bunge to water depletion and demonstrated effectiveness of the
      combined NMR and LC-DAD-MS methods in plant metabonomic analysis.

PMID- 20044833
TI  - Functional delivery of a membrane protein into oocyte membranes using bicelles.
AB  - Voltage-gated potassium channel modulatory membrane protein KCNE3 was
      overexpressed and purified into both micelles and bicelles. Remarkably,
      microinjection of KCNE3 in bicelles into Xenopus oocytes resulted in functional
      co-assembly with the human KCNQ1 channel expressed therein. Microinjection of
      LMPC micelles containing KCNE3 did not result in channel modulation, indicating
      that bicelles sometimes succeed at delivering a membrane protein into a cellular
      membrane when classical micelles fail. Backbone NMR resonance assignments were
      completed for KCNE3 in both bicelles and LMPC, indicating that the secondary
      structure distribution in KCNE3's N-terminus and transmembrane domains exhibits
      only modest differences from that of KCNE1, even though these KCNE family members
      have very different effects on KCNQ1 channel function.

PMID- 20044835
TI  - Chinese human liver proteome project: a pathfinder of HUPO human liver proteome
      project.

PMID- 20044836
TI  - Characterization of the phosphoproteome in LNCaP prostate cancer cells by in-gel
      isoelectric focusing and tandem mass spectrometry.
AB  - Reversible protein phosphorylation forms the basis of cell signaling networks.
      Aberrations in protein phosphorylation have been linked to human diseases
      including cancer. Phosphoproteomics has recently emerged as an approach that
      focuses on analysis of protein phosphorylation on a global scale. We have
      recently developed a new methodology, termed in-gel IEF LC-MS/MS, and we have
      adapted this methodology for phosphoproteome analysis. Here, we report on the
      application of in-gel IEF LC-MS/MS to the mapping of the phosphoproteome in the
      LNCaP human prostate cancer cell line. The analytical methodology used in the
      study included separation of the LNCaP proteins by in-gel isoelectric focusing
      (IEF), digestion of the proteins with trypsin, enrichment of the digests for
      phosphopeptides with Immobilized Metal Ion Affinity Chromatography (IMAC),
      analysis of the enriched digests by LC-MS/MS, and identification of the
      phosphorylated peptides/proteins through searches of a protein sequence database.
      With this analytical platform, we have characterized over 600 different
      phosphorylation sites in 296 phosphoproteins. This panel of the LNCaP
      phosphoproteins is 3-fold larger than the panel obtained in our previous work,
      which attests to the power of the chosen analytical methodology. The
      characterized phosphoproteins are functionally diverse and include a number of
      proteins relevant to cancer.

PMID- 20044838
TI  - Patterned p-doping of InAs nanowires by gas-phase surface diffusion of Zn.
AB  - Gas phase p-doping of InAs nanowires with Zn atoms is demonstrated as an
      effective route for enabling postgrowth dopant profiling of nanostructures. The
      versatility of the approach is demonstrated by the fabrication of high
      performance gated diodes and p-MOSFETs. High Zn concentrations with electrically
      active content of approximately 1 x 10(19) cm(-3) are achieved which is essential
      for compensating the electron-rich surface layers of InAs to enable heavily p
      doped structures. This work could have important practical implications for the
      fabrication of planar and nonplanar devices based on InAs and other III-V
      nanostructures which are not compatible with conventional ion implantation
      processes that often cause severe lattice damage with local stoichiometry
      imbalance.

PMID- 20044834
TI  - Biochemical mechanisms of resistance to small-molecule protein kinase inhibitors.
AB  - Protein kinases have emerged as one of the most frequently targeted families of
      proteins in drug discovery. While the development of small-molecule inhibitors
      that have the potency and selectivity necessary to be effective cancer drugs is
      still a formidable challenge, there have been several notable successes in this
      area over the past decade. However, in the course of the clinical use of these
      inhibitors, it has become apparent that drug resistance is a recurring problem.
      Because kinase inhibitors act by targeting a specific kinase or set of kinases,
      there is a strong selective pressure for the development of mutations that hinder
      drug binding but preserve the catalytic activity of these enzymes. To date,
      resistance mutations to clinically approved kinase inhibitors have been
      identified in a number of kinases. This review will highlight recent work that
      has been performed to understand how mutations in the kinase catalytic domain
      confer drug resistance. In addition, recent experimental efforts to predict
      potential sites of clinical drug resistance will be discussed.

PMID- 20044839
TI  - Quantitative description of aggregation and dissociation of polystyrene chains in
      cyclohexane solutions by resonance light scattering technique.
AB  - The resonance light scattering (RLS) technique based on a conventional
      fluorescence spectrophotometer was used to quantitatively describe the
      aggregation and dissociation of polystyrene (PS) in cyclohexane solution during
      cyclic heating and cooling. Transitions in conformation of PS molecules and
      aggregation of PS chains in the course of phase separation were revealed. The
      results indicated that PS chains changed from random coils to collapsed globules
      and then aggregated when temperature decreased. In contrast, when the system is
      heated, the chain aggregates were initially swelled and followed by gradual
      dissociation. Subsequently, the conformation of PS chains returned to the
      original state. Kinetics of phase separation of the PS solution was analyzed,
      which allowed estimation of the apparent activation energy.

PMID- 20044840
TI  - Large area protein patterning reveals nanoscale control of focal adhesion
      development.
AB  - Focal adhesion development in cells adherent to surface bound fibronectin
      presented as 200, 500, or 1000 nm diameter circular patches or as homogeneous
      controls is studied by fluorescence and scanning electron microscopy. Fundamental
      cellular processes such as adhesion, spreading, focal adhesion and stress fiber
      formation are shown to be dependent on the spatial distribution of ligands at
      this scale. Large area samples enable the study of whole cell populations and
      opens for new potential applications.

PMID- 20044841
TI  - Wafer-scale synthesis and transfer of graphene films.
AB  - We developed means to produce wafer scale, high-quality graphene films as large
      as 3 in. wafer size on Ni and Cu films under ambient pressure and transfer them
      onto arbitrary substrates through instantaneous etching of metal layers. We also
      demonstrated the applications of the large-area graphene films for the batch
      fabrication of field-effect transistor (FET) arrays and stretchable strain gauges
      showing extraordinary performances. Transistors showed the hole and electron
      mobilities of the device of 1100 +/- 70 and 550 +/- 50 cm(2)/(V s) at drain bias
      of -0.75 V, respectively. The piezo-resistance gauge factor of strain sensor was
      approximately 6.1. These methods represent a significant step toward the
      realization of graphene devices in wafer scale as well as application in
      optoelectronics, flexible and stretchable electronics.

PMID- 20044842
TI  - Rapid sequencing of individual DNA molecules in graphene nanogaps.
AB  - I propose a technique for reading the base sequence of a single DNA molecule
      using a graphene nanogap to read the DNA's transverse conductance. Because
      graphene is a single atom thick, single-base resolution of the conductance is
      readily obtained. The nonlinear current-voltage characteristic is used to
      determine the base type independent of nanogap-width variations that cause the
      current to change by 5 orders of magnitude. The expected sequencing error rate is
      0% up to a nanogap width of 1.6 nm.

PMID- 20044843
TI  - Description of the outcomes of prior authorization of palivizumab for prevention
      of respiratory syncytial virus infection in a managed care organization.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of upper and
      lower respiratory tract infections in infants and young children. Most children
      are exposed to the virus before they are 2 years old and experience such symptoms
      as cough, fever, and irritability. In a select population of infants, the virus
      can cause hypoxemia and hospitalization. To avoid hospitalization, good infection
      control practices should be employed, and for those infants at high risk,
      prophylaxis with palivizumab is indicated. Palivizumab has been shown to reduce
      hospitalization rates in high-risk infants by 50%. Because of the high cost of
      palivizumab, it is prudent to use this medication in the population in which it
      will be most effective. The American Academy of Pediatrics (AAP) established the
      criteria for those infants who would benefit the most from palivizumab
      prophylaxis, and these criteria were the foundation for a prior authorization
      (PA) program to determine coverage of palivizumab in a health plan of
      approximately 500,000 members. OBJECTIVE: To (a) analyze the appropriateness of
      this PA program for palivizumab used prophylactically for RSV, and (b) determine
      the financial cost associated with the medication and disease for this health
      plan. METHODS: A 3-year, retrospective study was conducted from the 2005- 2006
      RSV season through the 2007-2008 season. The primary endpoint outcome was the
      hospitalization rate associated with RSV infection. Secondary endpoints included
      the cost of palivizumab and RSV-related emergency room (ER) utilization. Infants
      were placed into 2 groups: those who received PA approval for use of palivizumab
      and those who were denied coverage in the PA process. Disease-related
      hospitalization and ER visits were identified by at least 1 administrative claim
      containing either a primary or secondary ICD-9-CM code for any of the following:
      RSV (079.6), acute bronchiolitis caused by RSV (466.11), or pneumonia caused by
      RSV (480.1). Drug cost was defined as the health plan's allowed amount, which is
      based on a predefined fee schedule for the Current Procedural Terminology (CPT)
      code 90378 for palivizumab. Hospital and ER costs are the health plan allowed
      amounts (health plan plus member cost) based on the reimbursement rates
      determined by diagnosis related group (DRG) and other coding, and the plan
      allowed amount based on DRGs includes all services and drugs provided in the
      specific encounter. Drug cost avoided was calculated as the average cost of
      palivizumab treatment per episode multiplied by the number of infants denied
      coverage of palivizumab over the 3-year study period. RESULTS: Over 3 RSV seasons
      through May 2008, the PA program received 1,090 requests for coverage of
      palivizumab, of which 348 (31.9%) were denied. Of 742 PA-approved infants, 629
      received at least 1 dose of palivizumab. The mean (SD) gestational age of the PA
      denied group was 34.4 (2.5) weeks versus 32.5 (4.0) weeks for the PA-approved
      group (P < 0.001). In the PA-denied group, 14 infants (4.0%) were subsequently
      hospitalized with an RSV infection, and 5 (1.4%) had an RSV-related ER visit
      versus 40 (6.4%) hospitalized and 14 (2.2%) with ER visits for infants in the PA
      approved group (P = 0.055 and P = 0.019, respectively); 15 (4.3%) of the PA
      denied group had either a hospitalization or an ER visit versus 42 (6.6%) in the
      PA-approved group (P = 0.060). One patient in the palivizumab PA-approved group
      died. Over the 3 RSV seasons, the mean number of palivizumab doses and mean
      allowed palivizumab cost per treatment episode (per infant per season) were 3.64
      and $6,950, respectively, and the average allowed palivizumab cost was $7,702 per
      utilizing infant. Total per infant costs for palivizumab, RSV hospitalizations,
      and RSV-related ER visits were $8,534 for infants receiving palivizumab compared
      with $223 for those denied palivizumab coverage (P = 0.002). Drug cost avoidance
      associated with the PA program was estimated to be $2,418,600 (348 infants times
      $6,950 palivizumab cost per episode) over the 3 RSV seasons. CONCLUSION: In a
      500,000-member health plan, a PA program to restrict palivizumab use in
      accordance with AAP recommendations was associated with estimated palivizumab
      drug cost avoidance of more than $2.4 million over 3 years. There was no
      significant difference in the RSV-related hospitalization rate for the PA-denied
      versus the PA-approved groups, but the PA-denied group had a slightly lower rate
      of RSV-related ER visits.

PMID- 20044844
TI  - Medical utilization associated with palivizumab compliance in a commercial and
      managed medicaid health plan.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower
      respiratory tract infections and hospitalization in infants. Palivizumab is
      currently the only available agent for prevention of RSV infection in high-risk
      infants. This high-cost injectable requires monthly dosing during the RSV season.
      Compliance with the injection schedule is important in the prevention of RSV
      infection and respiratory complications. Managed care organizations have an
      interest in the relationship between compliance with the palivizumab dosing
      schedule and respiratory-related medical outcomes such as emergency room (ER)
      visits, physician office visits, and hospitalizations. OBJECTIVE: To evaluate
      respiratory-related medical outcomes and cost for infants who were prescribed and
      received palivizumab in accordance with the dosing schedule recommended by the
      American Academy of Pediatrics (AAP) in 2006 versus those who did not. METHODS: A
      retrospective claims analysis was conducted to assess the relationship between
      compliance with the palivizumab dosing schedule and respiratory-related medical
      visits and costs in a western Pennsylvania managed care organization composed of
      approximately 307,000 commercial and 92,000 Medicaid members. De-identified
      pharmacy and medical claims data were extracted for infants (0-24 months) who met
      prior authorization criteria and who received at least 1 dose of palivizumab
      during the 2006-2007 RSV season (October 15, 2006, to April 15, 2007). Patient
      compliance was based on (a) starting palivizumab on time, (b) receiving the
      expected number of injections, and (c) no more than a 37-day gap between
      palivizumab claims. Medical utilization (physician office visits, ER visits, and
      hospital admissions) was analyzed by comparing medical services (with respiratory
      related ICD-9-CM codes) for the compliant versus noncompliant groups. Net health
      plan costs (after subtraction of member cost share) were compared for compliant
      versus noncompliant groups for (a) palivizumab-only pharmacy cost; (b) the cost
      of RSV-related medical services; and (c) the cost of all respiratory-related
      medical services, excluding those provided during the inpatient newborn stay. The
      associations between compliance and other patient variables were assessed using
      the Mann-Whitney U test for nonparametric data and Pearson chi-square or Fisher's
      Exact tests for categorical data. RESULTS: Of the 245 infants who received
      palivizumab during the 2006- 2007 RSV season, 151 (61.6%) were first-season
      recipients of palivizumab, and 131 (53.5%) were male; 145 (59.2%) belonged to a
      Medicaid benefit plan, and 100 (40.8%) belonged to a commercial benefit plan; and
      73 (29.8%) were deemed to be compliant with the 2006 AAP recommended palivizumab
      dosing schedule. Fourteen (19.2%) of compliant infants had at least 1 respiratory
      related hospital admission compared with 37 (21.5%) of noncompliant infants (P =
      0.734). The proportions of infants with at least 1 respiratory-related physician
      office visit were also similar for the 2 groups, 60.3% (n = 44) for compliant
      infants versus 64.5% (n = 111) for noncompliant infants (P = 0.564). There was a
      significant difference in the proportion of infants with at least 1 respiratory
      related ER visit, 15.1% (n = 11) of compliant infants versus 28.5% (n = 49) of
      noncompliant infants (P = 0.034), but there were no RSV-related ER visits in
      either group and no significant differences between the groups in the proportion
      with at least 1 RSV-related office visit (9.6% for compliant infants vs. 5.8% for
      noncompliant infants, P = 0.284). RSV-related hospitalization occurred in 0
      (0.0%) compliant and 2 (1.2%) noncompliant infants (P = 1.000). Compliant infants
      had significantly higher median per patient palivizumab pharmacy costs ($10,416)
      compared with noncompliant infants ($7,605, P = 0.011). However, median total
      (palivizumab and respiratory-related medical) costs for the 2 groups did not
      significantly differ (P = 0.189). CONCLUSION: About 30% of the infants who
      received palivizumab during the 2006-2007 RSV season were compliant with dosing
      recommendations. Compliance was associated with a lower proportion of infants
      with at least 1 respiratory-related ER visit but not with any other study
      outcome, including the proportion of infants with at least 1 hospital admission
      or physician visit or any measure of RSV-related use. Median palivizumab per
      patient costs were higher for the compliant group, but there was no significant
      between-group difference in total median per patient cost (palivizumab drug plus
      respiratory-related medical cost).

PMID- 20044845
TI  - Economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in
      Korea.
AB  - BACKGROUND: Streptococcus pneumoniae (sp) is a leading cause of invasive and
      noninvasive bacterial disease in children. 7-valent pneumococcal conjugate
      vaccine (PCV-7) has been shown to significantly reduce the incidence of
      pneumococcal diseases, such as meningitis, bacteremia, pneumonia, and otitis
      media. Although PCV-7 was introduced in Korea in 2003, it is not yet included in
      the universal immunization program. OBJECTIVE: To evaluate the health outcomes,
      costs, and cost-effectiveness of universal vaccination with PCV-7 in Korean
      infants and to estimate the break-even price for PCV-7 from a societal
      perspective. METHODS: A decision analytic model was used to evaluate the cost
      effectiveness of immunization with PCV-7 in a birth cohort of Korean infants born
      in 2006. A universal vaccination strategy was compared with no vaccination in
      terms of costs and life years gained (LYG) over a 5-year time horizon. The birth
      cohort size, incidence of disease, resource utilization, and associated costs
      were obtained from the Korea National Statistical Office, the Korean Centers for
      Disease Control and Prevention, the Korean National Health and Nutrition
      Examination Survey, and the Korean Ministry of Health and Welfare. Inputs on the
      probabilities of clinical treatment pathways (e.g., tympanostomy) were derived
      from international literature if data specific to Korea did not exist. To
      estimate the benefits of universal immunization, the serotype-specific efficacy
      of PCV-7 was derived from studies conducted by Northern California Kaiser
      Permanente and by the Finnish Otitis Media Vaccine Study and applied to the
      serotypes isolated in Korean children with sp infections. The effects of
      vaccination on quality of life, herd immunity, benefits after the first 5 years
      of life, and patient copayments were not considered. A 4-dose schedule was used
      in the base-case analysis. A 3-dose schedule was also evaluated. The assumed
      price per dose was Korean won (KW) 70,000 (approximately US$54; 2009 exchange
      rate US$1 = KW1,300). Univariate and probabilistic sensitivity analyses were
      performed. RESULTS: Implementing a 4-dose universal PCV-7 vaccination strategy in
      a birth cohort of 451,514 infants in Korea would prevent 96,728 cases of
      pneumococcal-related infections (591 meningitis, 1,379 bacteremia, 43,950
      pneumonia, and 50,808 otitis media cases) and 218 deaths (199 discounted deaths
      averted, 575 discounted LYG over 5 years). The medical and nonmedical cost burden
      of pneumococcal diseases offset with vaccination was KW44,033 million (US$33.87
      million). The incremental discounted cost of universal vaccination was estimated
      to be KW86,384 million (US$66.45 million). The incremental cost per LYG was
      KW150.2 million (US$115,549) for the 4-dose schedule and KW103.91 million
      (US$79,955) for the 3-dose schedule. The break-even costs were KW22,100 and
      KW28,100 per dose for the 4- and 3-dose schedules, respectively. CONCLUSIONS:
      Universal PCV-7 vaccination of infants in Korea could substantially reduce
      pneumococcal disease morbidity, mortality, and related costs by preventing
      pneumococcal infections. However, at current market prices for the vaccine, a
      universal vaccination strategy is not cost-effective. The literature suggests
      that factors not considered in this analysis, including vaccine price reduction
      and indirect effects on public health (e.g., herd immunity), have the potential
      to make the public health impact and cost-effectiveness of universal PCV-7
      vaccination in Korea more favorable.

PMID- 20044846
TI  - Utilization management opportunities for palivizumab for prophylaxis of
      respiratory syncytial virus complications in infants.

PMID- 20044847
TI  - Medication therapy management and collaborative drug therapy management.

PMID- 20044848
TI  - The AMCP format for formulary submissions version 3.0.

PMID- 20044849
TI  - The mortality gap between urban and rural Canadians: a gendered analysis.
AB  - INTRODUCTION: The primary purpose of this article is to demonstrate the role that
      age, gender, and place play in rural-urban differences in mortality, in order to
      better develop policy to reduce these differences. METHODS: In 2006, the Canadian
      Institute for Health Research published a major epidemiological investigation
      into the morbidity and mortality experience of Canadians, using mortality data as
      well as the 2004 Canadian Community Health Survey. Using these data, gender
      differences in mortality across the rural-urban continuum were further explored.
      The proportion of excess deaths occurring in each of the four different types of
      rural places, relative to deaths in urban places, were calculated for different
      gender and age groups. RESULTS: Differences in mortality across the urban-rural
      continuum are mainly driven by people under 45 years, and are particularly due to
      deaths caused by injury and poisoning, motor vehicle accident (MVA) and suicide.
      The proportion of excess deaths relative to urban places for those under 45 years
      increases with decreasing age. Remote places have the highest excess in mortality
      for suicide, MVA, injury and poisoning, relative to urban places. CONCLUSION: The
      relative mortality for young girls living in rural compared with urban places is
      similar to the relative mortality for young rural boys. There is, therefore, a
      need for prevention policies targeted at both boys and girls to prevent suicide,
      injury/poisoning, and MVAs in rural, and especially in remote, places.

PMID- 20044851
TI  - Public health interventions for arthritis: expanding the toolbox of evidence
      based interventions.
AB  - BACKGROUND: Since 1999, the Centers for Disease Control and Prevention's (CDC)
      Arthritis Program has worked to improve the quality of life for people with
      arthritis, in part by funding state health departments to disseminate physical
      activity (PA) and self-management education (SME) interventions. Initially, only
      one SME and two PA interventions were considered evidence-based and appropriate
      for people with arthritis. The purposes of this article are to describe the
      processes and criteria used to screen new or existing intervention programs and
      report the results of that screening, including an updated list of recommended
      intervention programs. METHODS: A series of three sets of screening criteria was
      created in consultation with subject matter experts: arthritis appropriateness,
      adequacy of the evidence base, and implementability as a public health
      intervention. Screening interventions were categorized as Recommended, Promising
      Practices, Watch List, Future Possibility, or Unlikely to Meet criteria based on
      how well the intervention met the screening criteria. RESULTS: A total of 15
      packaged PA interventions and six SME interventions were screened. Three PA and
      three SME interventions met all three sets of criteria and were added to the list
      of recommended public health interventions for use by CDC-funded state arthritis
      programs. An additional two SME interventions are developing the infrastructure
      for public health dissemination and were categorized as Promising Practices, and
      six PA interventions have evaluations underway and are on the Watch List.
      CONCLUSIONS: The CDC Arthritis Program identified arthritis-appropriate
      interventions that can be used effectively and efficiently in public health
      settings to improve the quality of life of people with arthritis. The screening
      criteria used offer a guide to intervention developers on necessary
      characteristics of interventions for use in public health settings. The expanded
      menu of interventions is beneficial to clinical care and public health
      professionals and, ultimately, to people with arthritis.

PMID- 20044852
TI  - Toward optimal health: a review of vaccine recommendations for women. Interview
      by Jodi R Godfrey.

PMID- 20044853
TI  - Making safe abortion services accessible in Ghana.

PMID- 20044854
TI  - Physical activity beliefs, barriers, and enablers among postpartum women.
AB  - BACKGROUND AND METHODS: Physical activity during postpartum is both a recommended
      and an essential contributor to maternal health. Understanding the beliefs,
      barriers, and enablers regarding physical activity during the postpartum period
      can more effectively tailor physical activity interventions. The objective of
      this study was to document self-reported beliefs, barriers, and enablers to
      physical activity among a cohort of women queried at 3 and 12 months postpartum.
      Five questions about beliefs and two open-ended questions about their main
      barriers and enablers regarding physical activity and exercise were asked of 667
      women at 3 months postpartum. Among the sample, 530 women answered the same
      questions about barriers and enablers to physical activity at 12 months
      postpartum. RESULTS: Agreement on all five beliefs statements was high (>or=89%),
      indicating that women thought that exercise and physical activity were
      appropriate at 3 months postpartum, even if they continued to breastfeed. For the
      cohort, the most common barriers to physical activity at both 3 and 12 months
      postpartum were lack of time (47% and 51%, respectively) and issues with child
      care (26% and 22%, respectively). No barrier changed by more than 5% from 3 to 12
      months postpartum. For the cohort, the most common enablers at 3 months
      postpartum were partner support (16%) and desire to feel better (14%). From 3 to
      12 months postpartum, only one enabler changed by >5%; women reported baby
      reasons (e.g., baby older, healthier, not breastfeeding, more active) more often
      at 12 months than at 3 months postpartum (32% vs. 10%). Environmental/policy and
      organizational barriers and enablers were reported less often than intrapersonal
      or interpersonal barriers at both time points. CONCLUSIONS: A number of barriers
      and enablers were identified for physical activity, most of which were consistent
      at 3 and 12 months postpartum. This study provides information to create more
      successful interventions to help women be physically active postpartum.

PMID- 20044855
TI  - Preventing cervical cancer in the Latina population.
AB  - Cervical cancer causes great morbidity and mortality worldwide and in the United
      States. Infection with oncogenic human papillomavirus (HPV), the etiological
      agent of almost all cervical cancer cases, is common among sexually active women
      in the United States. Over the past 5 decades, the implementation of Papanicolaou
      screening programs in the United States has led to a significant decrease in
      cervical cancer cases. However, notable disparities in the incidence and
      mortality of cervical cancer and cervical screening rates among Hispanics in the
      United States remain. If current disparities persist without intervention, the
      Latina population in the United States may remain at a higher risk of developing
      and dying from cervical cancer. We discuss disparities in cervical cancer
      screening, incidence, and mortality among the Latina population, as well as the
      barriers that may propagate these disparities. We also address how these barriers
      can be overcome through the coordination of outreach programs and widespread
      prophylactic HPV vaccination to reduce cervical cancer disparities in Latinas.

PMID- 20044856
TI  - Timing of alcohol use and the incidence of premenstrual syndrome and probable
      premenstrual dysphoric disorder.
AB  - BACKGROUND: Relatively little is known about factors that influence the initial
      development of premenstrual syndrome (PMS) and premenstrual dysphoric disorder
      (PMDD), although these conditions are common in reproductive age women and are
      associated with substantial impairment. Previous studies have observed higher
      alcohol use in prevalent PMS/PMDD patients compared with controls, but it is
      unknown if drinking predisposes women to developing these disorders or is instead
      influenced by symptom experience. METHODS: To address this, we conducted a case
      control study nested within the prospective Nurses' Health Study II (NHS2).
      Participants were a subset of women aged 27-44 and free from PMS at baseline
      (1991), including 1057 women who developed PMS over 10 years of follow-up, 762 of
      whom also met criteria consistent with PMDD, and 1968 control women. Alcohol use
      at various time periods, before and after onset of menstrual symptoms, was
      assessed by questionnaire. RESULTS: Overall, alcohol use was not strongly
      associated with the incidence of PMS and probable PMDD. Relative risks (RR) for
      women with the highest cumulative alcohol use vs. never drinkers were 1.19 (95%
      confidence interval [CI] 0.84-1.67) for PMS and 1.28 (95% CI 0.86-1.91) for PMDD,
      although results did suggest a positive relationship in leaner women (p
      trend=0.002). Women who first used alcohol before age 18 had an RR of PMS of 1.26
      (95% CI 0.91-1.75) compared with never drinkers; the comparable RR for PMDD was
      1.35 (95% CI 0.93-1.98). CONCLUSIONS: These findings suggest alcohol use is not
      strongly associated with the development of PMS and PMDD, although early age at
      first use and long-term use may minimally increase risk.

PMID- 20044857
TI  - Rapid eye movement sleep behavior disorder in women: relevance to general and
      specialty medical practice.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a treatable parasomnia
      involving dream-enacting behaviors that is considered to be a male-predominant
      disorder. However, it is speculated that underrecognition of RBD among female
      patients in part contributes to the male predominance, probably because women
      have less aggressive and violent RBD behaviors. We conducted a literature review
      focused primarily on women with RBD, in which the age of onset of RBD, types of
      nocturnal behaviors, presence of dream enactment, polysomnographic findings,
      clinical course, treatment response, male/female ratio, comorbid diagnoses, and
      medications were tabulated and discussed. RBD was found to primarily affect
      middle-aged and older women and those with a broad range of neurological
      disorders. As the link between RBD and neurodegenerative disorders, such as
      Parkinson's disease, becomes increasingly apparent, including the delayed
      emergence of parkinsonism in patients initially diagnosed with idiopathic RBD,
      primary care and specialty physicians should be aware of RBD in women, its
      potential complications, its excellent response to clonazepam, and its
      association with neurological disorders and older age groups.

PMID- 20044858
TI  - Factors associated with preclinical disability and frailty among HIV-infected and
      HIV-uninfected women in the era of cART.
AB  - BACKGROUND: HIV-associated immune injury is hypothesized to increase the risk of
      preclinical disability and frailty via inflammatory pathways. We investigated the
      role of CD4+ T cell depletion and clinical AIDS on preclinical disability and
      frailty in HIV-positive women with a history of combination antiretroviral
      therapy (cART) and HIV-negative women. METHODS: This was a cross-sectional study
      nested within the Women's Interagency HIV Study (WIHS), a prospective cohort
      study initiated in 1994 across five U.S. cities. Questionnaires and tests were
      performed by 573 HIV-negative and 1206 HIV-positive women. Prevalence ratios were
      computed using regression models. RESULTS: Severe CD4+ cell depletion was an
      independent predictor of slowness, weakness, and frailty in HIV-positive women
      compared with HIV-negative women. Women with CD4+ counts<100 cells/mm3 were 0.13
      seconds slower to complete 4 meters (95% CI 0.06-0.21), 1.25 kg weaker (95% CI 
      2.31--0.19), and had 2.7 times higher prevalence of frailty (95% CI 1.46-5.01).
      CONCLUSIONS: This study is one of the largest studies to administer performance
      based tests to investigate disability and frailty in HIV-positive women. HIV
      positive women with intact immune systems and without a history of clinical AIDS
      were no different from HIV-negative women on tests of slowness, weakness, and
      frailty phenotype.

PMID- 20044859
TI  - Lack of knowledge of hormone receptor status and use of endocrine therapy in
      invasive breast cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the level of understanding in
      women with newly diagnosed invasive breast cancer of the key clinical features of
      their disease that are important determinants in treatment decision making.
      METHODS: The 1684 women aged between 26 and 88 years at diagnosis enrolled in a 5
      year cohort study were asked by questionnaire about their estrogen receptor (ER)
      and progesterone receptor (PR) status and about their past or current treatment
      with adjuvant endocrine therapy. Information was linked with their ER and PR
      status determined from the histopathology report. Logistic regression analysis
      was used to explore the relationship between age and education status and the
      likelihood of being able to correctly report hormone receptor status, as well as
      the relationship between the likelihood of receiving adjuvant endocrine therapy
      and knowledge of hormone receptor status in women who were ER or PR positive.
      RESULTS: Not being able to correctly report hormone receptor status was
      associated with being older and having a lower level of education. Of women who
      were ER positive or PR positive or both and were at least 40 weeks from
      diagnosis, having received some form of endocrine therapy was significantly
      associated with self-identification as being ER or PR positive (OR=1.82, 95% CI
      1.24-2.68, p=0.002), even when age was taken into account. CONCLUSIONS: That self
      knowledge of hormone receptor status was independently associated with likelihood
      of receiving endocrine therapy suggests that the methods of helping women
      understand the nature of their breast cancer are worthy of review.

PMID- 20044860
TI  - Symptoms and pregnancy outcomes associated with extreme weight loss among women
      with hyperemesis gravidarum.
AB  - OBJECTIVE: To report the weight loss and associated symptoms experienced by a
      large cohort of women with hyperemesis gravidarum (HG). METHODS: Data were
      obtained from an HG website registry, where women with HG were recruited on-line.
      Respondents were included if they experienced at least 1 live birth>27 weeks'
      gestation. Extreme weight loss was defined as a loss of >15% of prepregnancy
      weight. RESULTS: Of the 819 women surveyed, 214 (26.1%) met criteria for extreme
      weight loss. These women were twice as likely to be Hispanic or nonwhite. Extreme
      weight loss (p<0.001) was associated with indicators of the severity of HG, such
      as hospitalization and use of parenteral nutrition, and with multiple symptoms
      during pregnancy, such as gallbladder and liver dysfunction, renal failure, and
      retinal hemorrhage. Among all women surveyed, 22.0% reported that symptoms lasted
      throughout pregnancy; this finding was nearly twice as likely among women with
      extreme weight Loss: 63 of 214 (29.4%) vs. 117 of 605 (19.3%) (OR=1.73, 95% CI
      1.2-2.5, p=0.003). For some women, symptoms continued postpartum and included
      food aversions, muscle pain, nausea, and posttraumatic stress. Approximately 16%
      of babies were born prematurely, and 8% reportedly weighed <2500 g. Among women
      with extreme weight loss, 9.3% reported having a child with a behavioral
      disorder. CONCLUSIONS: Extreme weight loss is common among women with HG,
      suggesting that HG is a form of prolonged starvation in pregnancy and that the
      long-term effects of this condition on women and their offspring warrant further
      investigation.

PMID- 20044861
TI  - Risk of lung cancer following nonmalignant respiratory conditions among
      nonsmoking women living in Shenyang, Northeast China.
AB  - BACKGROUND: There has been conflicting evidence about possible associations
      between nonmalignant respiratory conditions (NMRCs) and subsequent risk of lung
      cancer. Determination of whether or not there is such an association has
      potential importance for managing NMRCs, for screening of lung cancer, and for
      understanding mechanisms of carcinogenesis. METHODS: A hospital-based, case
      control study involving interviews with 226 female nonsmoking lung cancer
      patients and 279 matching population controls was conducted in Shenyang,
      Northeast China, between January 2004 and December 2007. A standardized interview
      collected information on a variety of potential risk factors, including a history
      of physician-diagnosed NMRCs (pulmonary tuberculosis, chronic bronchitis,
      emphysema, asthma, and bronchiectasis), and age/year in which each condition was
      first diagnosed. Multivariate logistic regression analyses were applied to assess
      the associations between NMRCs and subsequent lung cancer risk. RESULTS: Compared
      with those without, subjects with a history of NMRC experience greater risk of
      lung cancer (OR=2.0, 95% CI 1.2-3.4), particularly following a diagnosis of
      pulmonary tuberculosis (OR=4.7, 95% CI 1.6-13.2). The results from subgroup
      analysis, when limited to small cell lung cancer, showed a 6.2-fold increase in
      lung cancer risk among asthmatics (95% CI 1.5-25.8). However, there was no
      evidence of a significant association between chronic bronchitis and lung cancer.
      CONCLUSIONS: This study strengthens the evidence linking NMRCs, especially
      pulmonary tuberculosis, to lung cancer even in lifelong nonsmoking women.

PMID- 20044862
TI  - Treatment considerations for bacterial vaginosis and the risk of recurrence.
AB  - BACKGROUND: Recommended regimens for the treatment of bacterial vaginosis (BV)
      have similar efficacy; thus, the choice of treatment should consider additional
      factors such as risk of BV recurrence and side effect profile. The purpose of
      this study was to investigate BV recurrence rates and rates of acquiring
      vulvovaginal candidiasis (VVC) after different BV treatments in a commercially
      insured population. METHODS: Private administrative insurance claims from 2004 to
      2006 were used. Study subjects were continuously enrolled females 12-50 years of
      age who filled prescriptions for BV treatment (n=32,268). The four BV treatments
      (single-dose clindamycin vaginal cream (2%), multiple-dose clindamycin vaginal
      regimens, vaginal metronidazole, and oral metronidazole) were compared for rates
      of recurrent BV and VVC after treatment using multivariate analyses. Covariates
      included sociodemographic and clinical characteristics. RESULTS: Overall, the
      rate of BV recurrence (2.7%), and VVC posttreatment (2.9%) were low. Women who
      were treated with single-dose clindamycin vaginal cream (2%) showed no
      significant difference from women treated with oral metronidazole in the
      likelihood of BV recurrence. However, women who received other vaginal treatments
      were significantly more likely to experience BV recurrence compared with women
      who received oral metronidazole (p<0.01). Moreover, women who were treated with
      single-dose clindamycin vaginal cream (2%) and vaginal metronidazole were
      significantly less likely to have VVC compared with those treated with oral
      metronidazole (p<0.01). CONCLUSIONS: This study suggests that single-dose
      clindamycin vaginal cream (2%) may be a good alternative to oral metronidazole
      for the treatment of BV, given the low rates of recurrence and subsequent VVC
      demonstrated in this analysis.

PMID- 20044863
TI  - Sexual risk in "mostly heterosexual" young women: influence of social support and
      caregiver mental health.
AB  - BACKGROUND: Female youth who describe their sexual orientation as "mostly
      heterosexual," rather than exclusively heterosexual, display greater sexual risk,
      yet reasons for this greater risk are not understood. Research is needed to
      identify factors responsible for health disparities in this population comprising
      the majority of youth who report a minority sexual orientation. METHODS: We
      compared indicators of perceived social support, parental/caregiver mental
      health, and sexual risk (age at first sexual intercourse, lifetime history of a
      sexually transmitted infection (STI), lifetime number of sexual partners) among
      33 young women describing themselves as mostly heterosexual and 337 indicating
      they were 100% heterosexual (aged 18-24 years) participating in an urban,
      multiethnic, community-based cohort study. Linear, logistic, and Cox proportional
      hazards regression were used to test whether social support and caregiver mental
      health explained greater sexual risk among mostly heterosexual compared with
      heterosexual participants. RESULTS: Compared with exclusively heterosexuals,
      mostly heterosexuals reported less social support from family (p=0.01) and
      friends (p=0.02) and were more likely to report primary male caregiver (though
      not primary female caregiver) histories of depression (p<0.0001), treatment for
      depression (p<0.0001), and problems with drug use (p=0.005). Differences in
      perceived family social support and caregiver mental health and substance use
      partially mediated relationships between sexual orientation and sexual risk.
      CONCLUSIONS: Compared with exclusively heterosexual female youth, mostly
      heterosexual female youth may have poorer relationships with their family and
      others in their social networks, and this may contribute to their elevated health
      risks. Additional research is needed to understand causal mechanisms responsible
      for sexual orientation disparities in sexual risk.

PMID- 20044864
TI  - Disparities in cancer screening: acceptance of Pap smears among homeless women.
AB  - AIMS: Cervical cancer is a preventable disease through screening and early
      treatment. Rates of cervical cancer are higher in impoverished women, including
      homeless women. This study assessed the acceptance of free and accessible Pap
      smears offered to homeless women in a respite care setting. METHODS: A
      convenience sample of 205 adult women receiving respite care at a facility for
      homeless people in Boston, Massachusetts, between 2004 and 2007 were offered
      screening for cervical cancer during routine encounters with the medical staff
      during their stay. Rates of acceptance of screening as well as medical and
      sociodemographic information were collected on the women. RESULTS: Of 205 women
      enrolled in the study, 129 (63%) were in need of screening and offered a Pap
      smear; 80 (62%) accepted and 49 (38%) declined. Of those who agreed to be tested,
      56 (70%) had a Pap smear performed, resulting in 10 (18%) atypical results
      (atypical squamous cells of undetermined significance [ASCUS] or low-grade
      squamous intraepithelial lesion [LGSIL]) and 15 (27%) benign findings needing
      follow-up (e.g., vaginitis without evidence of malignancy). CONCLUSIONS: A large
      proportion of homeless women receiving respite care decline a free Pap smear
      despite being in medical need of cervical cancer screening. Access and cost may
      not be the only barriers to screening among homeless women, and new and
      innovative approaches to screening in vulnerable populations need to be
      investigated in order to close the disparity gap.

PMID- 20044865
TI  - The context of informal abortions in rural Ghana.
AB  - AIMS: This qualitative study explores the context of unsafe abortion in rural
      Ghana with the aim of identifying areas that should be considered when
      operationalizing abortion-related reproductive health strategies. METHODS: Data
      come from eleven narratives about planned or attempted abortions and seven
      narratives of abortion-related deaths. These individual data are supplemented by
      data from ten focus group discussions. RESULTS: Communities describe abortions as
      dangerous and, if they become public knowledge, shameful. Despite this, abortions
      were understood as necessary for some women in some situations, but secrecy was
      paramount. Women carefully chose their confidants based on the anticipated
      reaction and did so for advice about cheap and effective methods or for financial
      assistance. Complications were usually managed at home. When complications were
      taken to the health facility, the abortion was often not disclosed. Women
      reported trying sequential abortion methods, starting with cheaper milder methods
      and, if these attempts failed, resorting to harsher more expensive methods.
      Access to pharmaceuticals and finances also determined the method used. Financial
      hardship, interruption of education, and being unmarried were the most frequently
      cited reasons for abortions. CONCLUSIONS: Unsafe abortion is an important public
      health issue in Ghana. Current strategies to reduce abortion-related deaths
      include increasing the provision of safe abortion services. For the strategy to
      be successful, services should be accessible, affordable, and confidential, and
      discourse with communities and health workers to break the public silence about
      abortion is needed.

PMID- 20044866
TI  - Maternal depression and the quality of marital relationship: a 14-year
      prospective study.
AB  - AIMS: This study aims to investigate the bidirectional association between
      symptoms of depression and quality of marital relationship in a population-based
      cohort of women. METHODS: The bidirectional association was examined
      longitudinally in over 3694 women participating in the Mater-University study of
      Pregnancy, Brisbane, Australia, over a 14-year period. Women were interviewed 3-5
      days postdelivery and again when the child was 6 months, 5 years, and 14 years of
      age. A transition model was developed to examine changes in exposures and risk
      factors over the 14 years of follow-up. RESULTS: Nearly 40% of the women with
      depressive symptoms continued to report symptoms, and a similar proportion of
      women who reported being in a poor quality marital relationship remained in a
      poor quality relationship over long periods of time. Approximately 1 in 10 women
      who had not reported symptoms of depression or a poor relationship in the
      previous phase did so at the subsequent phase. The bidirectional relationships
      between depressive symptoms and quality of marital relationship are both
      consistent and strong. Negative changes in either symptoms of depression or
      quality of marital relationship predicted a poor outcome. The estimated
      population attributable risk was similar for both depressive symptoms and quality
      of the marital relationship. CONCLUSIONS: The findings from this study suggest
      that symptoms of depression and quality of relationship are strongly associated
      with each other and that this association is bidirectional. Clinical intervention
      in poor quality marital relationships represents a logical approach to addressing
      symptoms of depression in women. Similarly, there needs to be a focus on family
      outcomes for those women with impaired mental health.

PMID- 20044867
TI  - Gender differences in cardiac rehabilitation outcomes: do women benefit equally
      in psychological health?
AB  - BACKGROUND: Psychological factors are important in the etiology and prognosis of
      coronary heart disease (CHD). Cardiac rehabilitation (CR) aims to reduce
      psychological distress, besides other somatic risk factors. Studies have shown
      that CR is effective in reducing psychological distress, but little is known
      about gender-specific outcome differences. Our objective was to examine whether
      women and men benefit equally from outpatient CR in terms of reduction in
      psychological distress and whether women show more impaired psychological health
      at baseline of CR than do men. METHODS: We enrolled 441 CHD patients (mean age
      58+/-11 years, 79.8% men) who underwent a 12-week outpatient CR program.
      Psychological dimensions, namely, anxiety, depression, vital exhaustion, social
      inhibition, and negative affect, were assessed at baseline and post-CR.
      Multivariate analysis of variance (MANOVA), controlling for age, disease
      severity, and exercise capacity, was applied to test for gender-specific
      differences at baseline and change between baseline and post-CR. In addition,
      gender-specific effect sizes were calculated for the change on psychological
      dimensions. RESULTS: Women and men did not differ on any psychological measure at
      baseline of CR. The effect sizes show small to moderate treatment effects on the
      psychological dimensions assessed. Gender had a significant impact on change on
      the dimensions vital exhaustion (F=5.040(df=1), p<0.05) and social inhibition
      (F=5.74(df=1), p<0.05). Women showed larger change on social inhibition and
      smaller change on vital exhaustion than men. CONCLUSIONS: Women and men do not
      differ in the extent of psychological distress at baseline of CR, which could be
      explained also by the exclusion of highly distressed women from treatment. CR is
      less effective among women with regard to vital exhaustion and more effective
      with regard to social inhibition compared with men in a sample of low distressed
      patients.

PMID- 20044868
TI  - Metabolic syndrome and elevated C-reactive protein in breast cancer survivors on
      adjuvant hormone therapy.
AB  - AIMS: As the efficacy of treatment for breast cancer has improved, particularly
      with the use of antiestrogenic therapies, there is an increasing population of
      long-term breast cancer survivors who seeks care with unique health issues. These
      patients may be at increased risk for cardiovascular disease (CVD) resulting from
      excess adiposity and treatment effects. Metabolic syndrome (MetS) and elevated C
      reactive protein (CRP), two predictors of CVD, have not been fully evaluated in
      overweight breast cancer survivors on hormone-modulating agents. METHODS:
      Anthropometric measures, including weight, height, waist and hip circumferences;
      clinical laboratory assessments, including lipids, glucose, glycoslyated
      hemoglobin (HbA1c), insulin, and high sensitivity CRP; and body composition and
      blood pressure (BP) were collected from overweight breast cancer survivors
      (n=42). Select measures were used to derive MetS using the National Cholesterol
      Education Program Adult Treatment Panel III (NCEP-ATP III) diagnostic criteria.
      RESULTS: Participants had a mean body weight of 83.8 kg and body mass index (BMI)
      of 31.4 kg/m2. Mean fasting glucose (98+/-12.9 mg/dL), HbA1c (6.0+/-0.5 mg/dL),
      cholesterol (199+/-33.7 mg/dL), and insulin (16+/-3.2 mg/dL) were all at the
      upper end of the normal range. MetS was diagnosed in 54.8% of overweight
      postmenopausal breast cancer survivors. CRP was moderately or severely elevated
      in 90.5% of the population (mean of 5.1+/-5.3 mg/dL). CONCLUSIONS: In our sample,
      overweight breast cancer survivors commonly have MetS and elevated CRP that place
      them at increased risk for cardiovascular and other metabolic diseases. If
      replicated in a larger sample, this warrants close medical monitoring to prevent
      and reduce morbidity and mortality unrelated to breast cancer.

PMID- 20044869
TI  - Social ties in relation to health status of low-income Brazilian women.
AB  - BACKGROUND: Social support resources are thought to buffer stressful life events
      and have been associated with numerous health outcomes in industrialized
      countries. Because the nature of supportive relationships varies by culture and
      social class, we studied the relationship of informal social support and networks
      to self-rated health among low-income women in northeastern Brazil. METHODS:
      Participants included 595 randomly sampled mothers from nine low-income
      communities in Teresina, Piaui, Brazil. Data on sociodemographic variables,
      social support, quality of the partner relationship, and self-rated health were
      collected cross-sectionally in 2002. Using multivariable logistic regression, we
      modeled the association between different aspects of social support and self
      rated health. RESULTS: Poor or fair health was reported by 47% of participants.
      Women with poor partner relationships had an increased likelihood of poor or fair
      health (OR 1.7, 95% CI 1.1-2.7), as did those with no material support for food
      or money (OR 1.6, 95% CI 1.2, 2.0) and no support to resolve a conflict (OR 1.5,
      95% CI 1.1, 2.1). Likewise, women with the lowest scores of the Medical Outcomes
      Study (MOS) social support survey were more likely than other women to report
      poor or fair health (OR 1.5, 95% CI 1.0, 2.1). CONCLUSIONS: Poor quality of a
      partner relationship, lack of support to resolve a conflict, and lack of material
      support as well as such sociodemographic variables as low education, poor
      sanitation, and depressive symptomatology are associated with lower health status
      in a population of low-income women from northeastern Brazil.

PMID- 20044870
TI  - Prevalence and risk factors of high-risk human papillomavirus in female sex
      workers in Spain: differences by geographical origin.
AB  - OBJECTIVE: To study the influence of socioeconomic variables, lifestyles, and
      sexual behaviors on the prevalence of high-risk human papillomavirus (HR-HPV)
      infection in female sex worker (FSW) according to their geographic origin in
      Alicante, Spain. METHODS: This is a cross-sectional study of 549 FSW attending an
      AIDS information and prevention center from May 2003 to December 2004. Face-to
      face interviews were carried out. HR-HPV was determined through Digene HR-HPV
      Test. Hybrid Capture II-positive samples (Digene Corp., Gaithersburg, MD) for PCR
      were directly sequenced. Data were analyzed using multiple logistic regression.
      RESULTS: HR-HPV prevalence was 28% in Spaniards, 32% in Latin Americans, 32% in
      Eastern Europeans, 16% in sub-Saharan Africans, and 65% in North Africans
      (p=0.04). Lower HR-HPV prevalence was associated with higher age, higher
      education, and higher body mass index (BMI) (p values for trend<0.05). In
      multivariate analyses, the effects of geographical origin, age, and education
      were maintained, together with time in sex work; women engaged for >1 year had a
      lower HR-HPV prevalence (OR 0.57, 95% CI 0.36-0.91) compared with those engaged
      <1 year. HR-HPV-16 was the most common type (n=23, 24%), followed by HR-HPV-18
      and HR-HPV-31, (n=11, 11%), respectively. CONCLUSIONS: HR-HPV prevalence is very
      high in FSW and varies by geographic origin. Women of younger age and lower
      education level and those engaged in sex work for <1 year showed the highest
      prevalence, making them a priority group for cervical cancer prevention programs.

PMID- 20044872
TI  - Work as a nurse and a midwife and adverse pregnancy outcomes: a Finnish
      nationwide population-based study.
AB  - OBJECTIVE: To assess whether work as a nurse and a midwife during pregnancy
      increases the risk of adverse pregnancy outcomes. METHODS: We identified from the
      1990-2006 Finnish Medical Birth Registry all singleton births to nurses
      (n=109,542), midwives (n=3,009), and teachers (n=23,454) (referents). The main
      outcomes were sexual differentiation, low and high birth weight, preterm and
      postterm delivery, small and large for gestational age, and perinatal death.
      RESULTS: The prevalence of low birth weight (2.9% vs. 2.5%), preterm delivery
      (4.4% vs. 4.1%), postterm delivery (4.7% vs. 4.1%), small for gestational age
      (1.8% vs. 1.4%), perinatal death (0.45% vs. 0.41%) and stillbirth (0.30% vs.
      0.25%) was higher among the newborns of nurses than those of teachers. The
      adjusted odds ratio (OR) from generalized estimating equations was 1.17 (95%
      confidence interval [CI] 1.07-1.26) for low birth weight, 1.09 (95% CI 1.02-1.16)
      for preterm delivery, 1.11 (95% CI 1.03-1.18) for postterm delivery, 1.17 (95% CI
      1.05-1.30) for small for gestational age, 1.12 (95% CI 0.90-1.35) for perinatal
      death, and 1.27 (95% CI 0.98-1.56) for stillbirth. For midwives, the risk of
      small for gestational age (OR=1.25, 95% CI 0.95-1.55) was elevated, but the 95%
      CI included unity. There was no substantial difference in the sex distribution.
      CONCLUSIONS: This study provides evidence that work as a nurse may reduce fetal
      growth and duration of pregnancy. The inference is based on the newborns of
      teachers as the reference group. However, the prevalence of most of the outcomes
      was higher among the newborns of all other working women combined than in the
      newborns of both nurses and teachers.

PMID- 20044871
TI  - The association of patient-physician gender concordance with cardiovascular
      disease risk factor control and treatment in diabetes.
AB  - BACKGROUND: Gender concordance between patients and their physicians is related
      to prevention screening and other quality indicators. Research suggests female
      physicians may place greater emphasis on preventive care than male physicians;
      however, little is known about whether physician gender and patient-physician
      gender concordance are associated with cardiovascular disease (CVD) risk factor
      levels and treatment. Our objective was to examine associations between patient
      gender, physician gender, and their interaction with CVD risk factor control,
      medication adherence, and treatment intensification in diabetes. METHODS: In this
      study, 157,458 Kaiser Permanente Northern California adult diabetes patients with
      a primary care physician (PCP) were assessed for above target levels of
      hemoglobin A1c (HbA1c) (>or=8%), low-density lipoprotein cholesterol (LDL-C)
      (>or=100 mg/dL), and systolic blood pressure (SBP>or=130 mm Hg) in 2005.
      Medication adherence and appropriate CVD treatment intensification were assessed
      using pharmacy data. Probit models assessed the adjusted marginal effects of
      patient gender, PCP gender, and their interaction on control, adherence, and
      intensification. RESULTS: Female patients had lower adjusted rates of LDL-C (46%
      vs. 55%, p<0.001) and SBP control (52% vs. 60%, p<0.001) than males. Female
      patients of female PCPs had the highest adjusted rates of HbA1c control of the
      four patient-physician gender dyads (70% vs. 66%-68%, p<0.05). Male patients were
      more likely than female patients to receive treatment intensification for high
      SBP (60% vs. 57%, p<0.001). Female PCPs were more likely than their male
      counterparts to intensify therapy for hyperlipidemia and hypertension.
      CONCLUSIONS: Patient and physician gender and gender concordance are modestly
      associated with CVD risk factor control and treatment in diabetes. Further
      understanding of these differences could lead to improved CVD outcomes for women.

PMID- 20044873
TI  - The co-occurrence of intimate partner violence and syphilis among pregnant women
      in Bolivia.
AB  - BACKGROUND: Intimate partner violence (IPV) and sexually transmitted infections
      (STI) are epidemics that disproportionately affect women. This study determined
      IPV prevalence and the association between IPV and positive syphilis tests among
      pregnant women attending antenatal clinics in three provinces in Bolivia.
      METHODS: We administered structured questionnaires to women after syphilis
      testing. The questionnaire included sociodemographic variables and four questions
      form the modified version of the Abuse Assessment Screen (AAS) to assess physical
      and sexual violence. RESULTS: Of 6002 women who completed the violence
      questionnaire and had a syphilis test, 20.4% (n=1227) reported physical or sexual
      abuse or both committed by their partner in the past year. Prevalence of positive
      syphilis tests was twice as high among women who reported IPV (8%) than among
      women who did not (4%) (p<0.01). Women's age (younger), education level (lower),
      occupation as homemaker, being in a consensual union, more previous pregnancies,
      lower economic status, and language spoken at home (Spanish and an indigenous
      language), as well as history of IPV in the past 12 months, were significantly
      associated with positive syphilis tests in bivariate analysis. History of IPV
      remained significantly associated with positive syphilis tests in multivariate
      analysis (OR 1.59, 95% CI 1.23-2.07). In addition, low education among women's
      partners and having at least one previous pregnancy were positively associated
      with IPV in multivariate analysis. CONCLUSIONS: There is a significant
      association between history of partner violence and a positive syphilis test
      among pregnant women, suggesting that syphilis can be an important negative
      health consequence of IPV. Bolivia's new maternal and infant health program in
      antenatal clinics, which includes universal syphilis screening, should also
      provide screening and follow-up care for IPV.

PMID- 20044875
TI  - Concentrations of free vascular endothelial growth factor in the maternal and
      foetal circulations during pregnancy: a cross-sectional study.
AB  - OBJECTIVE: To investigate the concentrations of free plasma vascular endothelial
      growth factor (VEGF) in the maternal and foetal circulations of normal term
      pregnancies. METHODS: Free plasma VEGF was measured from plasma of umbilical cord
      and maternal blood by ELISA for each of 20 normal pregnancies delivering at term
      at an altitude of 3100 m. Spearman's correlation coefficient was used to test for
      correlation between values and clinical maternal and neonatal data. Student's 't'
      test was used to test for differences between samples from male and female
      neonates. RESULTS: Free plasma VEGF was undetectable from maternal samples, but
      it was detectable in the cord blood (mean, 560.3775 pg/ml, median, 145.84 pg/ml,
      range, 22.56-2653.5). No differences were found between neonates sex, and no
      correlation was found with clinical maternal and neonatal data. CONCLUSION:
      Circulating VEGF is usually bound to the soluble form of its receptor 1 (sFlt-1).
      High levels of sFlt-1 are secreted by the syncytiotrophoblast during pregnancy,
      and so free plasma VEGF is undetectable in the maternal circulation. In contrast,
      our findings are the first to show free plasma VEGF in the umbilical circulation.
      We speculate that this free VEGF may promote angiogenesis in the foetus and
      placenta. Our data imply that sFlt-1 is not present in the cord blood, and that
      secretion by the syncytiotrophoblast is polarised to its apical surface. Further
      investigations are required to test this hypothesis.

PMID- 20044876
TI  - Umbilical vein blood flow at 11 + 0 to 13 + 6 weeks of gestation.
AB  - OBJECTIVE: To establish reference intervals for fetal umbilical vein (UV)
      diameter, UV time averaged maximum velocity (TAMXV) and UV flow (UVBF) at 11 + 0
      to 13 plus; 6 weeks of gestation and to determine the intraobserver reliability
      of these measurements. METHODS: We considered, in a cross-sectional study, 162
      fetuses from uncomplicated singleton pregnancies at 11 + 0 to 13 + 6 weeks of
      gestation. UV diameter and TAMXV were measured in its intraabdominal portion by
      real-time and Doppler ultrasonography and UVBF calculated. Relationships between
      these parameters and fetal crown rump length were tested by regression analysis.
      In 25 cases UVBF was measured twice by the same investigator and the
      intraobserver agreement of these measurements was calculated. RESULTS: A
      significant increase was evidenced in the gestational age period considered in UV
      diameter (r = 0.729, p < 0.0001), TAMXV (r = 0.691, p < 0.0001) and UVBF (r =
      0.777, p < 0.0001). UVBF increased from 2.26 ml/min at 11 weeks to 15.62 ml/min
      at 13 + 6 weeks of gestation. The intraobserver ICCs were 0.96, 0.92 and 0.88,
      respectively, for UV diameter, TAMXV and UVBF. CONCLUSIONS: In normal fetuses, UV
      diameter, TAMVX and flow increase between 11 + 0 and 13 + 6 weeks of gestation.
      In this gestational age interval, the calculation of UV blood flow and its
      components shows an intraobserver agreement reliable enough for clinical use.

PMID- 20044877
TI  - Polymorphisms of the angiotensin converting enzyme gene in early-onset and late
      onset pre-eclampsia.
AB  - OBJECTIVE: The aim of this study was to investigate differences in maternal and
      infant ACE genotypes in early-onset and later-onset pre-eclampsia/toxemia (PET).
      METHODS: We conducted a case-control study of 22 cases of early-onset pre
      eclampsia (before 34 weeks gestation), 38 cases of later-onset pre-eclampsia
      (after 34 weeks gestation), and 108 healthy controls delivered at term (38-40
      weeks gestation) within a stable Caucasian population. Maternal venous blood and
      cord bloods were obtained for serum angiotensin converting enzyme (ACE) activity,
      ACE genotype, and acid-base status. RESULTS: Mothers who developed early-onset
      PET were more likely to be homozygous for the deletion allele of the ACE genotype
      (DD) than mothers with late-onset PET or uncomplicated pregnancies (12/22 (55%)
      vs. 7/38 (18%) vs. 22/105 (21%), respectively; OR 2.96 [95% confidence intervals
      (CI) 1.37-6.31]. Infants of mothers with early-onset PET were more likely to be
      homozygous for the DD genotype than infants of mothers with late-onset PET or
      controls (7/19 (37%) vs. 9/36 (25%) vs. 11/78 (14%); OR 2.51 (95% CI 1.12-5.61).
      There were no differences in maternal or infant ACE activities in relation to
      onset of pre-eclampsia. CONCLUSIONS: Our findings suggest an association between
      the DD genotype of the ACE gene and early-onset but not later-onset pre-eclampsia
      which may give a partial explanation for the higher recurrence risk with early
      onset pre-eclampsia.

PMID- 20044878
TI  - Placement of laminaria tents does not improve time to delivery in patients
      undergoing second trimester labor induction with misoprostol.
AB  - OBJECTIVE: We sought to determine whether placement of laminaria tents improve
      time to delivery compared with misoprostol alone in second trimester labor
      induction. METHODS: We retrospectively reviewed all patients undergoing second
      trimester labor induction. Patients with ruptured membranes, abruption, cervical
      dilation and chorioamnionitis at presentation were excluded. Complications were
      defined as chorioamnionitis, retained placenta or other surgical procedures.
      Patients who received laminaria and vaginal misoprostol, 200 microg every 12 h,
      were compared to those who received misoprostol without laminaria. RESULTS: Forty
      three patients met inclusion criteria, 19 underwent induction with misoprostol
      alone and 24 with laminaria and misoprostol. The median times to fetal and
      placenta deliveries were 16.4 and 0.0 h in the misoprostol group, and 20.6 and
      0.2 h in the laminaria group. There was no difference in complications. Post-hoc
      power analysis revealed >80% power to detect a difference in time to delivery of
      >12 h, and >90% power to detect a difference in time to placental delivery of >
      or =30 min. CONCLUSIONS: Placement of laminaria does not improve fetal or
      placental delivery times in patients undergoing second trimester pregnancy
      termination by labor induction.

PMID- 20044879
TI  - Chiral effects in adrenocorticolytic action of o,p'-DDD (mitotane) in human
      adrenal cells.
AB  - Adrenocortical carcinoma (ACC) is a rare malignant disease with poor prognosis.
      The main pharmacological choice, o,p'-DDD (mitotane), produces severe adverse
      effects. Since o,p'-DDD is a chiral molecule and stereoisomers frequently possess
      different pharmacokinetic and/or pharmacodynamic properties, we isolated the two
      o,p'-DDD enantiomers, (R)-(+)-o,p'-DDD and (S)-(-)-o,p'-DDD, and determined their
      absolute structures. The effects of each enantiomer on cell viability and on
      cortisol and dehydroepiandrosterone (DHEA) secretion in the human adrenocortical
      cell line H295R were assessed. We also assayed the o,p'-DDD racemate and the m,p'
      and p,p'-isomers. The results show small but statistically significant
      differences in activity of the o,p'-DDD enantiomers for all parameters tested.
      The three DDD isomers were equally potent in decreasing cell viability, but p,p'
      DDD affected hormone secretion slightly less than the o,p'- and m,p'-isomers. The
      small chiral differences in direct effects on target cells alone do not warrant
      single enantiomer administration, but might reach importance in conjunction with
      possible stereochemical effects on pharmacokinetic processes in vivo.

PMID- 20044880
TI  - Immunotoxicity and hematotoxicity induced by tetrachloroethylene in egyptian dry
      cleaning workers.
AB  - The immune and hematological systems can be a target for environmental
      contaminants with potential adverse effects, so the purpose of this study is to
      provide documentation on immunotoxicity and hematotoxicity of
      tetrachloroethylene, which is widely used in dry cleaning in Egypt. This study
      was carried out on 80 adult males. Subjects designated as controls (n = 40) were
      healthy persons and others were tetrachloroethylene-exposed dry-cleaning workers
      (n = 40). The controls and tetrachloroethylene-exposed workers were then divided
      into four equal groups (20 individuals/group): group I, control group never
      smoking; group II, smoking control group; and groups III and IV,
      tetrachloroethylene-exposed nonsmoking and smoking workers, respectively. Blood
      level of tetrachloroethylene, complete blood count, immunoglobulins (IgA, IgM,
      IgG, and IgE), the total numbers of white blood cells (WBC), and leukocyte
      differential counts, as well as interferon gamma (IFN-gamma) and interleukin-4
      (IL-4), were measured. The immunotoxicity of tetrachloroethylene appeared in the
      form of an increase in serum immunoglobulin E in nonsmoking and smoking
      tetrachloroethylene-exposed workers, while the serum immunoglobulins A, M, and G
      levels showed no significant change in all studied groups. In addition, our
      results demonstrated a significant increase in white cell count, lymphocytes,
      natural killer (NK; CD3+CD16CD56+) cells, and B (CD19+) lymphocytes. The increase
      in WBC and lymphocytes may be attributed to allergic reaction. Moreover, serum
      and lymphocytic interlukin-4 levels were significantly increased in nonsmoking
      and smoking tetrachloroethylene-exposed workers. Tetrachloroethylene exposure is
      associated with immunotoxicity, which may lead to the augmentation of allergic
      diseases or appearance of autoimmune reaction.

PMID- 20044881
TI  - Ozone exposure enhances mast-cell inflammation in asthmatic airways despite
      inhaled corticosteroid therapy.
AB  - Asthmatics are recognised to be more susceptible than healthy individuals to
      adverse health effects caused by exposure to the common air pollutant ozone.
      Ozone has been reported to induce airway neutrophilia in mild asthmatics, but
      little is known about how it affects the airways of asthmatic subjects on inhaled
      corticosteroids. We hypothesised that ozone exposure would exacerbate the pre
      existent asthmatic airway inflammation despite regular inhaled corticosteroid
      treatment. Therefore, we exposed subjects with persistent asthma on inhaled
      corticosteroid therapy to 0.2 ppm ozone or filtered air for 2 h, on 2 separate
      occasions. Lung function was evaluated before and immediately after exposure,
      while bronchoscopy was performed 18 h post exposure. Compared to filtered air,
      ozone exposure increased airway resistance. Ozone significantly enhanced
      neutrophil numbers and myeloperoxidase levels in airway lavages, and induced a
      fourfold increase in bronchial mucosal mast cell numbers. The present findings
      indicate that ozone worsened asthmatic airway inflammation and offer a possible
      biological explanation for the epidemiological findings of increased need for
      rescue medication and hospitalisation in asthmatic people following exposure to
      ambient ozone.

PMID- 20044882
TI  - Conference summary: International Biomass Smoke Health Effects (IBSHE).
AB  - The Centers for Disease Control and Prevention (CDC) and the University of
      Montana's Center for Environmental Health Sciences (CEHS) co-hosted a conference
      entitled "International Biomass Smoke and Health Effects" in Missoula, MT, on
      August 21 and 22, 2007. The goal of this conference was to bring together experts
      from diverse fields to review the state of the science in several key areas
      involving biomass smoke research, as well as identify future research directions.
      Researchers, physicians, and representatives from regulatory agencies from around
      the country and world met for a cross-disciplinary exploration of many issues
      related to biomass smoke research. Major topics of discussion included risk
      assessment, biomarkers of exposure, toxicology and animal study design, health
      outcomes measures/study design, and communications gaps. In addition to multiple
      presentations, breakout sessions were focused on identifying future research
      directions. In this issue of Inhalation Toxicology, we present the findings from
      each of these breakout sessions in an effort to summarize what is known in these
      key areas, and to identify those emerging issues in the field of biomass smoke
      research.

PMID- 20044883
TI  - Biomass smoke exposures: health outcomes measures and study design.
AB  - Epidemiological studies of biomass smoke health effects have been conducted in a
      variety of settings and with a variety of study designs. The Health Effects
      Workgroup discussed several approaches for the investigation of health effects in
      communities exposed to wood smoke from nearby wildland fires, intentional
      agricultural burning, or residential biomass burning devices such as woodstoves
      or cookstoves. This presentation briefly reviews observational and intervention
      studies that have been conducted within these exposure settings. The review is
      followed by a summary of discussion points among the workgroup members with
      particular emphasis on study design and the use of biomarkers for assessing
      outcomes in biomass smoke-exposed populations.

PMID- 20044884
TI  - Knowing your lines but missing your cue: rostral prefrontal lesions impair
      prospective memory cue detection, but not action-intention superiority.
AB  - Prospective memory (PM) deficits are a common consequence of lesions to PFC, but
      their underlying neurocognitive mechanisms and processes are poorly understood.
      Here, we report on a patient, Z. P., who suffers from a chronic focal PM deficit,
      while other cognitive functions including memory are intact. His lesion involves
      right polar PFC (Brodmann's areas 10 and 9). Z. P. was very impaired on tasks
      that require detection of PM cues during an ongoing task. He was impaired
      regardless of whether the PM cues involved effortful or nearly effortless
      detection on the part of controls. By contrast, on tasks that tap the underlying
      (implicit) representations of intentions to perform an action, Z. P. showed
      normal patterns of intention superiority effects (ISEs) for to-be-performed
      actions and an inhibition effect for prospective actions after they had been
      performed. Thus, this is the first report of a neuropsychological dissociation
      between preserved privileged representation of prospective intentions and
      impaired detection of cues that support the opportune recovery of PM. Our data
      are compatible with the "gateway hypothesis" of rostral PFC, but also suggest
      there are components that are unique to PM and that remain intact after lesions
      to this region.

PMID- 20044885
TI  - The functional and neural mechanism of action preparation: roles of EBA and FFA
      in voluntary action control.
AB  - Ideomotor theory claims that actions are cognitively represented and accessed via
      representations of the sensory effects they evoke. Previous studies provide
      support for this claim by showing that the presentation of action effects primes
      activation in corresponding motor structures. However, whether people actually
      use action-effect representations to control their motor behavior is not yet
      clear. In our fMRI study, we had participants prepare for manual or facial
      actions on a trial-by-trial basis, and hypothesized that preparation would be
      mediated by the cortical areas that code for the perceptual effects of these
      actions. Preparing for manual action induced higher activation of hand-related
      areas of motor cortex (demonstrating actual preparation) and of the extrastriate
      body area, which is known to mediate the perception of body parts. In contrast,
      preparing for facial action induced higher activation of face-related motor areas
      and of the fusiform face area, known to mediate face perception. These
      observations provide further support for the ideomotor theory and suggest that
      visual imagery might play a role in voluntary action control.

PMID- 20044887
TI  - Inhibitory control and the frontal eye fields.
AB  - Inhibitory control mechanisms are important in a range of behaviors to prevent
      execution of motor acts which, having been planned, are no longer necessary.
      Ready examples of this can be seen in a range of sports, such as cricket and
      baseball, where the choice between execution or inhibition of a bat swing must be
      made in a brief time interval. The role of the FEFs, an area typically described
      in relation to eye movement functions but also involved in visual processes, was
      investigated in an inhibitory control task using transcranial magnetic
      stimulation (TMS). A stop signal task with manual responses was used, providing
      measures of impulsivity and inhibitory control. TMS over FEF had no effect on
      response generation (impulsivity, indexed by go signal RT) but disrupted
      inhibitory control (indexed by stop signal RT). This is the first demonstration
      of a role for FEF in this type of task in normal subjects in a task which did not
      require eye movements and complements previous TMS findings of roles for pre-SMA
      and inferior frontal gyrus (IFG) in inhibitory control.

PMID- 20044886
TI  - The emergence of perceived position in the visual system.
AB  - Representing object position is one of the most critical functions of the visual
      system, but this task is not as simple as reading off an object's retinal
      coordinates. A rich body of literature has demonstrated that the position in
      which we perceive an object depends not only on retinotopy but also on factors
      such as attention, eye movements, object and scene motion, and frames of
      reference, to name a few. Despite the distinction between perceived and retinal
      position, strikingly little is known about how or where perceived position is
      represented in the brain. In the present study, we dissociated retinal and
      perceived object position to test the relative precision of retina-centered
      versus percept-centered position coding in a number of independently defined
      visual areas. In an fMRI experiment, subjects performed a five-alternative forced
      choice position discrimination task; our analysis focused on the trials in which
      subjects misperceived the positions of the stimuli. Using a multivariate pattern
      analysis to track the coupling of the BOLD response with incremental changes in
      physical and perceived position, we found that activity in higher level areas-
      middle temporal complex, fusiform face area, parahippocampal place area, lateral
      occipital cortex, and posterior fusiform gyrus--more precisely reflected the
      reported positions than the physical positions of the stimuli. In early visual
      areas, this preferential coding of perceived position was absent or reversed. Our
      results demonstrate a new kind of spatial topography present in higher level
      visual areas in which an object's position is encoded according to its perceived
      rather than retinal location. We term such percept-centered encoding
      "perceptotopy".

PMID- 20044888
TI  - Learning shapes the representation of visual categories in the aging human brain.
AB  - The ability to make categorical decisions and interpret sensory experiences is
      critical for survival and interactions across the lifespan. However, little is
      known about the human brain mechanisms that mediate the learning and
      representation of visual categories in aging. Here we combine behavioral
      measurements and fMRI measurements to investigate the neural processes that
      mediate flexible category learning in the aging human brain. Our findings show
      that training changes the decision criterion (i.e., categorical boundary) that
      young and older observers use for making categorical judgments. Comparing the
      behavioral choices of human observers with those of a pattern classifier based
      upon multivoxel fMRI signals, we demonstrate learning-dependent changes in
      similar cortical areas for young and older adults. In particular, we show that
      neural signals in occipito-temporal and posterior parietal regions change through
      learning to reflect the perceived visual categories. Information in these areas
      about the perceived visual categories is preserved in aging, whereas information
      content is compromised in more anterior parietal and frontal circuits. Thus,
      these findings provide novel evidence for flexible category learning in aging
      that shapes the neural representations of visual categories to reflect the
      observers' behavioral judgments.

PMID- 20044889
TI  - Neural correlates of abstract verb processing.
AB  - The present study investigated the neural correlates of the processing of
      abstract (low imageability) verbs. An extensive body of literature has
      investigated concrete versus abstract nouns but little is known about how
      abstract verbs are processed. Spanish abstract verbs including emotion verbs
      (e.g., amar, "to love"; molestar, "to annoy") were compared to concrete verbs
      (e.g., llevar, "to carry"; arrastrar, "to drag"). Results indicated that abstract
      verbs elicited stronger activity in regions previously associated with semantic
      retrieval such as inferior frontal, anterior temporal, and posterior temporal
      regions, and that concrete and abstract activation networks (compared to that of
      pseudoverbs) were partially distinct, with concrete verbs eliciting more
      posterior activity in these regions. In contrast to previous studies
      investigating nouns, verbs strongly engage both left and right inferior frontal
      gyri, suggesting, as previously found, that right prefrontal cortex aids
      difficult semantic retrieval. Together with previous evidence demonstrating
      nonverbal conceptual roles for the active regions as well as experiential content
      for abstract word meanings, our results suggest that abstract verbs impose
      greater demands on semantic retrieval or property integration, and are less
      consistent with the view that abstract words recruit left-lateralized regions
      because they activate verbal codes or context, as claimed by proponents of the
      dual-code theory. Moreover, our results are consistent with distributed accounts
      of semantic memory because distributed networks may coexist with varying
      retrieval demands.

PMID- 20044890
TI  - Musicians and the metric structure of words.
AB  - The present study aimed to examine the influence of musical expertise on the
      metric and semantic aspects of speech processing. In two attentional conditions
      (metric and semantic tasks), musicians listened to short sentences ending in
      trisyllabic words that were semantically and/or metrically congruous or
      incongruous. Both ERPs and behavioral data were analyzed and the results were
      compared to previous nonmusicians' data. Regarding the processing of meter,
      results showed that musical expertise influenced the automatic detection of the
      syllable temporal structure (P200 effect), the integration of metric structure
      and its influence on word comprehension (N400 effect), as well as the reanalysis
      of metric violations (P600 and late positivities effects). By contrast, results
      showed that musical expertise did not influence the semantic level of processing.
      These results are discussed in terms of transfer of training effects from music
      to speech processing.

PMID- 20044891
TI  - Perceptual basis of redundancy gains in visual pop-out search.
AB  - The redundant-signals effect (RSE) refers to a speed-up of RT when the response
      is triggered by two, rather than just one, response-relevant target elements.
      Although there is agreement that in the visual modality RSEs observed with
      dimensionally redundant signals originating from the same location are generated
      by coactive processing architectures, there has been a debate as to the exact
      stage(s)--preattentive versus postselective--of processing at which coactivation
      arises. To determine the origin(s) of redundancy gains in visual pop-out search,
      the present study combined mental chronometry with electrophysiological markers
      that reflect purely preattentive perceptual (posterior-contralateral negativity
      [PCN]), preattentive and postselective perceptual plus response selection-related
      (stimulus-locked lateralized readiness potential [LRP]), or purely response
      production-related processes (response-locked LRP). As expected, there was an RSE
      on target detection RTs, with evidence for coactivation. At the
      electrophysiological level, this pattern was mirrored by an RSE in PCN latencies,
      whereas stimulus-locked LRP latencies showed no RSE over and above the PCN
      effect. Also, there was no RSE on the response-locked LRPs. This pattern
      demonstrates a major contribution of preattentive perceptual processing stages to
      the RSE in visual pop-out search, consistent with parallel-coactive coding of
      target signals in multiple visual dimensions [Muller, H. J., Heller, D., &
      Ziegler, J. Visual search for singleton feature targets within and across feature
      dimensions.

PMID- 20044892
TI  - Multisensory facilitation of behavior in monkeys: effects of stimulus intensity.
AB  - Multisensory stimuli can improve performance, facilitating RTs on sensorimotor
      tasks. This benefit is referred to as the redundant signals effect (RSE) and can
      exceed predictions on the basis of probability summation, indicative of
      integrative processes. Although an RSE exceeding probability summation has been
      repeatedly observed in humans and nonprimate animals, there are scant and
      inconsistent data from nonhuman primates performing similar protocols. Rather,
      existing paradigms have instead focused on saccadic eye movements. Moreover, the
      extant results in monkeys leave unresolved how stimulus synchronicity and
      intensity impact performance. Two trained monkeys performed a simple detection
      task involving arm movements to auditory, visual, or synchronous auditory-visual
      multisensory pairs. RSEs in excess of predictions on the basis of probability
      summation were observed and thus forcibly follow from neural response
      interactions. Parametric variation of auditory stimulus intensity revealed that
      in both animals, RT facilitation was limited to situations where the auditory
      stimulus intensity was below or up to 20 dB above perceptual threshold, despite
      the visual stimulus always being suprathreshold. No RT facilitation or even
      behavioral costs were obtained with auditory intensities 30-40 dB above
      threshold. The present study demonstrates the feasibility and the suitability of
      behaving monkeys for investigating links between psychophysical and
      neurophysiologic instantiations of multisensory interactions.

PMID- 20044893
TI  - A neurocomputational model of dopamine and prefrontal-striatal interactions
      during multicue category learning by Parkinson patients.
AB  - Most existing models of dopamine and learning in Parkinson disease (PD) focus on
      simulating the role of basal ganglia dopamine in reinforcement learning. Much
      data argue, however, for a critical role for prefrontal cortex (PFC) dopamine in
      stimulus selection in attentional learning. Here, we present a new computational
      model that simulates performance in multicue category learning, such as the
      "weather prediction" task. The model addresses how PD and dopamine medications
      affect stimulus selection processes, which mediate reinforcement learning. In
      this model, PFC dopamine is key for attentional learning, whereas basal ganglia
      dopamine, consistent with other models, is key for reinforcement and motor
      learning. The model assumes that competitive dynamics among PFC neurons is the
      neural mechanism underlying stimulus selection with limited attentional
      resources, whereas competitive dynamics among striatal neurons is the neural
      mechanism underlying action selection. According to our model, PD is associated
      with decreased phasic and tonic dopamine levels in both PFC and basal ganglia. We
      assume that dopamine medications increase dopamine levels in both the basal
      ganglia and PFC, which, in turn, increase tonic dopamine levels but decrease the
      magnitude of phasic dopamine signaling in these brain structures. Increase of
      tonic dopamine levels in the simulated PFC enhances attentional shifting
      performance. The model provides a mechanistic account for several phenomena,
      including (a) medicated PD patients are more impaired at multicue probabilistic
      category learning than unmedicated patients and (b) medicated PD patients opt out
      of reversal when there are alternative and redundant cue dimensions.

PMID- 20044894
TI  - Isn't it ironic? An electrophysiological exploration of figurative language
      processing.
AB  - Although the neurocognitive processes underlying the comprehension of figurative
      language, especially metaphors and idioms, have been studied extensively, less is
      known about the processing of irony. In two experiments using event-related brain
      potentials (ERPs), we examined the types of cognitive processes involved in the
      comprehension of ironic and literal sentences and their relative time course. The
      experiments varied in modality (auditory, visual), task demands (comprehension
      task vs. passive reading), and probability of stimulus occurrence. ERPs
      consistently revealed a large late positivity (i.e., P600 component) in the
      absence of an N400 component for irony compared to equivalent literal sentences
      independent of modality. This P600 was shown to be unaffected by the factors task
      demands and probability of occurrence. Taken together, the findings suggest that
      the observed P600 is related to irony processing, and might be a reflection of
      pragmatic interpretation processes. During the comprehension of irony, no
      semantic integration difficulty arises (absence of N400), but late inferential
      processes appear to be necessary for understanding ironic meanings (presence of
      P600). This finding calls for a revision of current models of figurative language
      processing.

PMID- 20044895
TI  - Cross-modal interactions during perception of audiovisual speech and nonspeech
      signals: an fMRI study.
AB  - During speech communication, visual information may interact with the auditory
      system at various processing stages. Most noteworthy, recent
      magnetoencephalography (MEG) data provided first evidence for early and
      preattentive phonetic/phonological encoding of the visual data stream--prior to
      its fusion with auditory phonological features [Hertrich, I., Mathiak, K.,
      Lutzenberger, W., & Ackermann, H. Time course of early audiovisual interactions
      during speech and non-speech central-auditory processing: An MEG study. Journal
      of Cognitive Neuroscience, 21, 259-274, 2009]. Using functional magnetic
      resonance imaging, the present follow-up study aims to further elucidate the
      topographic distribution of visual-phonological operations and audiovisual (AV)
      interactions during speech perception. Ambiguous acoustic syllables-
      disambiguated to /pa/ or /ta/ by the visual channel (speaking face)--served as
      test materials, concomitant with various control conditions (nonspeech AV
      signals, visual-only and acoustic-only speech, and nonspeech stimuli). (i) Visual
      speech yielded an AV-subadditive activation of primary auditory cortex and the
      anterior superior temporal gyrus (STG), whereas the posterior STG responded both
      to speech and nonspeech motion. (ii) The inferior frontal and the fusiform gyrus
      of the right hemisphere showed a strong phonetic/phonological impact
      (differential effects of visual /pa/ vs. /ta/) upon hemodynamic activation during
      presentation of speaking faces. Taken together with the previous MEG data, these
      results point at a dual-pathway model of visual speech information processing: On
      the one hand, access to the auditory system via the anterior supratemporal "what"
      path may give rise to direct activation of "auditory objects." On the other hand,
      visual speech information seems to be represented in a right-hemisphere visual
      working memory, providing a potential basis for later interactions with auditory
      information such as the McGurk effect.

PMID- 20044896
TI  - ERP correlates of word production before and after stroke in an aphasic patient.
AB  - Changes in brain activity characterizing impaired speech production after brain
      damage have usually been investigated by comparing aphasic speakers with healthy
      subjects because prestroke data are normally not available. However, when
      interpreting the results of studies of stroke patients versus healthy controls,
      there is an inherent difficulty in disentangling the contribution of
      neuropathology from other sources of between-subject variability. In the present
      work, we had an unusual opportunity to study an aphasic patient with severe
      anomia who had incidentally performed a picture naming task in an ERP study as a
      control subject one year before suffering a left hemisphere stroke. The
      fortuitous recording of this patient's brain activity before his stroke allows
      direct comparison of his pre- and poststroke brain activity in the same language
      production task. The subject did not differ from other healthy subjects before
      his stroke, but presented major electrophysiological differences after stroke,
      both in comparison to himself before stroke and to the control group. ERP changes
      consistently appeared after stroke in a specific time window starting about 250
      msec after picture onset, characterized by a single divergent but stable
      topographic configuration of the scalp electric field associated with a cortical
      generator abnormally limited to left temporal posterior perilesional areas. The
      patient's pattern of anomia revealed a severe lexical-phonological impairment and
      his ERP responses diverged from those of healthy controls in the time window that
      has previously been associated with lexical-phonological processes during picture
      naming. Given that his prestroke ERPs were indistinguishable from those of
      healthy controls, it seems highly likely that the change in his poststroke ERPs
      is due to changes in language production processes as a consequence of stroke.
      The patient's neurolinguistic deficits, combined with the ERPs results, provide
      unique evidence for the role of left temporal cortex in lexical-phonological
      processing from about 250 to 450 msec during word production.

PMID- 20044897
TI  - Insula and orbital frontal cortex activity underlying emotion interference
      resolution in working memory.
AB  - Previous research has shown that emotional information aids conflict resolution
      in working memory [WM; Levens, S. M., & Phelps, E. A. Emotion processing effects
      on interference resolution in working memory. Journal of Emotion, 8, 267-280,
      2008]. Using a recency-probes WM paradigm, it was found that positive and
      negative emotional stimuli reduced the amount of interference created when
      information that was once relevant conflicted with currently relevant
      information. To explore the neural mechanisms behind these facilitation effects,
      an event-related fMRI version of the recency-probes task was conducted using
      neutral and arousing positive and negative words as stimuli. Results replicate
      previous findings showing that the left and right inferior frontal gyrus (IFG) is
      involved in the interference resolution of neutral information and reveal that
      the IFG is involved in the interference resolution of emotional information as
      well. In addition, ROIs in the right and left anterior insula and in the right
      orbital frontal cortex (OFC) were identified that appear to underlie emotional
      interference resolution in WM. We conclude that the IFG underlies neutral and
      emotional interference resolution, and that additional regions of the anterior
      insula and OFC may contribute to the facilitation of interference resolution for
      emotional information. These findings clarify the role of the insula and OFC in
      affective and executive processing, specifically in WM conflict resolution.

PMID- 20044898
TI  - Cerebro-cerebellar interactions underlying temporal information processing.
AB  - The neural basis of temporal information processing remains unclear, but it is
      proposed that the cerebellum plays an important role through its internal clock
      or feed-forward computation functions. In this study, fMRI was used to
      investigate the brain networks engaged in perceptual and motor aspects of
      subsecond temporal processing without accompanying coprocessing of spatial
      information. Direct comparison between perceptual and motor aspects of time
      processing was made with a categorical-design analysis. The right lateral
      cerebellum (lobule VI) was active during a time discrimination task, whereas the
      left cerebellar lobule VI was activated during a timed movement generation task.
      These findings were consistent with the idea that the cerebellum contributed to
      subsecond time processing in both perceptual and motor aspects. The feed-forward
      computational theory of the cerebellum predicted increased cerebro-cerebellar
      interactions during time information processing. In fact, a psychophysiological
      interaction analysis identified the supplementary motor and dorsal premotor
      areas, which had a significant functional connectivity with the right cerebellar
      region during a time discrimination task and with the left lateral cerebellum
      during a timed movement generation task. The involvement of cerebro-cerebellar
      interactions may provide supportive evidence that temporal information processing
      relies on the simulation of timing information through feed-forward computation
      in the cerebellum.

PMID- 20044899
TI  - Differential contributions of the intraparietal sulcus and the inferior parietal
      lobe to attentional blink: evidence from transcranial magnetic stimulation.
AB  - When two targets (T1 and T2) are to be identified in rapid serial visual
      presentation, the response to T1 induces impairment of T2 report if T2 appears
      within 500 msec after T1 (attentional blink: AB). AB is thought to reflect
      temporal limitations of attention which affect target perception. Recent research
      suggests that the intraparietal sulcus (IPS) contributes to an attentional set
      associated with task goals, whereas the inferior parietal lobe (IPL) is
      associated with the disengagement and reorienting of attention to a relevant
      stimulus presented outside the current focus of attention. We investigated
      respective involvement of the IPS and the IPL in AB using transcranial magnetic
      stimulation (TMS). The results of Experiment 1 showed that the magnitude of AB
      deficit decreased TMS disrupted activity of the IPS after T1 onset. In addition,
      an increased AB deficit occurred when TMS was delivered over the IPS or IPL after
      T2 onset. In Experiment 2, where participants were instructed to ignore T1, they
      showed an AB-like T2 deficit only when TMS was delivered to the IPS after a T2
      onset. Findings are discussed in terms of hypotheses about the respective roles
      of the IPS, in realizing an attentional set, and the IPL, in contributing to a
      disengagement of attention (from T1 to T2) during an AB period.

PMID- 20044900
TI  - Verbal labels modulate perceptual object processing in 1-year-old children.
AB  - Whether verbal labels help infants visually process and categorize objects is a
      contentious issue. Using electroencephalography, we investigated whether
      possessing familiar or novel labels for objects directly enhances 1-year-old
      children's neural processes underlying the perception of those objects. We found
      enhanced gamma-band (20-60 Hz) oscillatory activity over the visual cortex in
      response to seeing objects with labels familiar to the infant (Experiment 1) and
      those with novel labels just taught to the infant (Experiment 2). No such effect
      was observed for objects that infants were familiar with but had no label for.
      These results demonstrate that learning verbal labels modulates how the visual
      system processes the images of the associated objects and suggest a possible top
      down influence of semantic knowledge on object perception.

PMID- 20044901
TI  - The neural substrates and timing of top-down processes during coarse-to-fine
      categorization of visual scenes: a combined fMRI and ERP study.
AB  - Spatial frequencies in an image influence visual analysis across a distributed,
      hierarchically organized brain network. Low spatial frequency (LSF) information
      may rapidly reach high-order areas to allow an initial coarse parsing of the
      visual scene, which could then be "retroinjected" through feedback into lower
      level visual areas to guide finer analysis on the basis of high spatial frequency
      (HSF). To test this "coarse-to-fine" processing scheme and to identify its neural
      substrates in the human brain, we presented sequences of two spatial-frequency
      filtered scenes in rapid succession (LSF followed by HSF or vice versa) during
      fMRI and ERPs in the same participants. We show that for low-to-high sequences
      (but not for high-to-low sequences), LSF produces a first increase of activity in
      prefrontal and temporo-parietal areas, followed by enhanced responses to HSF in
      primary visual cortex. This pattern is consistent with retroactive influences on
      low-level areas that process HSF after initial activation of higher order areas
      by LSF.

PMID- 20044902
TI  - Neural correlates of foreign-language learning in childhood: a 3-year
      longitudinal ERP study.
AB  - A foreign language (a language not spoken in one's community) is difficult to
      master completely. Early introduction of foreign-language (FL) education during
      childhood is becoming a standard in many countries. However, the neural process
      of child FL learning still remains largely unknown. We longitudinally followed
      322 school-age children with diverse FL proficiency for three consecutive years,
      and acquired children's ERP responses to FL words that were semantically
      congruous or incongruous with the preceding picture context. As FL proficiency
      increased, various ERP components previously reported in mother-tongue (L1)
      acquisition (such as a broad negativity, an N400, and a late positive component)
      appeared sequentially, critically in an identical order to L1 acquisition. This
      finding was supported not only by cross-sectional analyses of children at
      different proficiency levels but also by longitudinal analyses of the same
      children over time. Our data are consistent with the hypothesis that FL learning
      in childhood reproduces identical developmental stages in an identical order to
      L1 acquisition, suggesting that the nature of the child's brain itself may
      determine the normal course of FL learning. Future research should test the
      generalizability of the results in other aspects of language such as syntax.

PMID- 20044904
TI  - Evidence for the involvement of lamins in aging.
AB  - The molecular mechanisms that cause physiological aging are still not completely
      understood, most likely because of the complex nature of the aging process.
      Recent discoveries on segmental progeroid syndromes emphasize the importance of
      studying rare diseases to discover more common mechanisms. Since the
      identification of mutations in the LMNA gene that causes the segmental progeroid
      syndrome, Hutchinson-Gilford progeria syndrome (HGPS), there has been an
      increasing interest in the potential role for lamins in the normal aging process.
      Recent data provide support for the shared mechanisms between natural and
      pathological aging, and show that further studies of HGPS and segmental progeroid
      syndromes will be of use in solving the aging puzzle. In this review, we
      summarize the recent findings and discuss the existing evidence for an important
      functional link between lamins and the aging process. In addition, we discuss the
      evidence for a mechanism in which defects in lamins result in genomic instability
      and senescence.

PMID- 20044903
TI  - Effects of epsilon4 on object recognition in the non-demented elderly.
AB  - Previously we reported that apolipoprotein E (ApoE) epsilon4 negatively affects
      performance in the novel-image-novel-location (NINL) object recognition test in
      healthy non-demented elderly human study participants. In this study, the
      participants were invited to return for testing sessions 6 and 18 months after
      the baseline session. Using a longitudinal study design, effects of epsilon4 on
      NINL test performance were assessed in study "dropouts", participants that did
      not return for the second and/or third session(s), and "finishers", participants
      that returned for all sessions. There were effects of epsilon4 on dropout rates
      and NINL total scores as well as sub-scores in both dropouts and finishers. NINL
      total score was a predictor of epsilon4 participant dropout. Compared to non
      epsilon4 dropouts, epsilon4 dropouts had lower NINL scores. In contrast, epsilon4
      finishers had higher NINL scores than non-epsilon4 finishers. Thus, the NINL test
      could be a valuable tool in detecting pre-clinical signs of age-related cognitive
      impairments, particularly those associated with epsilon4 risk.

PMID- 20044906
TI  - SIRT1, a calorie restriction mimetic, in a new therapeutic approach for type 2
      diabetes mellitus and diabetic vascular complications.
AB  - The rising incidence of diabetes, metabolic syndrome, and subsequent vascular
      diseases is now a major public health problem in industrialized countries. New
      therapeutic strategies to prevent these diseases are urgently needed worldwide.
      It is well known that calorie restriction (CR) can retard the aging process in
      organisms ranging from yeast to rodents, and delay the onset of numerous age
      related diseases including diabetes. Molecules that mimic CR metabolically are
      therefore potentially new therapeutic targets for age-related diseases. Silent
      information regulator 2 (Sir2) is an important player in CR-mediated life span
      extension. There is also increasing evidence that one of the seven mammalian
      sirtuins, SIRT1, is involved in regulating cellular processes such as apoptosis.
      SIRT1 has also been implicated in glucose homeostasis and lipid metabolism in
      various tissues including adipose tissues, liver, pancreas, and skeletal muscle.
      This review summarizes current understanding of the biological functions of
      SIRT1, and discusses its potential as a pharmacological target for fighting
      metabolic and vascular diseases.

PMID- 20044907
TI  - Floating controlled drug delivery system of famotidine loaded hollow microspheres
      (microballoons) in the stomach.
AB  - Most of the floating systems have an inherent drawback of high variability in the
      GI transit time, invariably affecting the bioavailability of drug. An attempt has
      been made to develop floating drug delivery system for improving the drug
      bioavailability by prolongation of gastric residence time of famotidine in
      stomach. The floating microballoons were prepared using polymer Eudragit L-100 by
      solvent evaporation and diffusion technique. The prepared famotidine loaded
      microspheres were characterised for drug loading, entrapment, encapsulation
      efficiency, particle size distribution, surface morphology, differential scanning
      calorimetry, test for buoyancy, in-vitro release and in-vivo antiulcer studies.
      The results showed an increased drug loading, encapsulation and entrapment
      efficiency. The thermogram of the DSC showed that the drug was encapsulated in
      amorphous form and SEM studies revealed the discrete, spherical shaped spheres
      with rough surface and presence of holes on floating microspheres due high
      entrapment of PEG which are responsible for drug release and floating ability.
      The sizes of spheres were found between 20-120 microm which exhibited prolonged
      release (In-vitro > 8 h) and remained buoyant for > 10 h. The mean particle size
      increased and the drug release rate decreased at higher Eudragit L-100 polymer
      concentration. The in-vivo results showed significant antiulcer property of
      famotidine loaded microspheres when compared to control and standard group of
      rats by using pyloric ligation method. The mean volume of gastric secretion, mean
      pH and mean total acid for formulation treated group was calculated as 3.45+/
      0.88 ml, 5.65+/-0.74, and 114.15+/-1.80 mEq/L respectively.

PMID- 20044908
TI  - Formulation optimization of etoposide loaded PLGA nanoparticles by double
      factorial design and their evaluation.
AB  - Etoposide is one of the most commonly used drugs in chemotherapy of acute
      lymphocytic leukemia and acute myelogenous leukaemia. Etoposide has variable oral
      bioavailability ranging from 24-74% and has terminal half life of 1.5 hours by
      intravenous route. The conventional parenteral therapy causes inconvenience and
      pain to the patients as it has to be given through a continuous IV infusion over
      24-34 h. The present investigation was aimed at developing etoposide loaded
      biodegradable nanoparticles which would be a sustained release formulation and
      replace the conventional therapy of continuous intravenous administration.
      Nanoparticles were prepared by emulsion solvent evaporation method using high
      pressure homogenization. The process parameters like homogenization cycles (four)
      and homogenization pressure (10000 psi) were first optimized using a 3(2)
      factorial design based on response Y1(mean particle size of 98+/-1nm). Then a 32
      factorial design was carried out to study the effect of two independent
      variables, ratio of drug and polymer (X1) and surfactant concentration (X2) on
      the two responses to obtain their optimized values, percentage entrapment
      efficiency (Y2, 83.12+/-8.3%) and mean particle size (Y3, 105+/-5.4 nm) for
      Etoposide loaded PLGA Nanoparticles. Contour plots and response surface plots
      showed visual representation of relationship between the experimental responses
      and the set of input variables. The adequacy of the regression model was verified
      by a check point analysis. The zeta potential values ranged between -23.0 to 
      34.2 mV, indicating stability. Sucrose was used as cryoprotectant during
      lyophilization. DSC and XRD studies indicated that etoposide was present in the
      amorphous phase and may have been homogeneously dispersed in the PLGA matrix. The
      electron micrographs showed spherical, discrete and homogenous particles. Drug
      release study showed that etoposide loaded PLGA nanoparticles sustained release
      up to 72h. The release from the nanoparticles followed first order kinetics and
      mechanism of drug release was Fickian. Stability studies indicated that it was
      best to store nanoparticle formulations in the freeze dried state at 2-8 degrees
      C where they remained stable in terms of both size and drug content upto three
      months.

PMID- 20044909
TI  - Development of repaglinide loaded solid lipid nanocarrier: selection of
      fabrication method.
AB  - Repaglinide solid lipid nanoparticles (RG-SLN) were fabricated using stearic acid
      as lipid. Pluronic F68 (PLF68) and soya lecithin were used as a stabilizer. SLNs
      were prepared by modified solvent injection and ultrasonication methods. SLNs
      prepared with modified solvent injection method have larger particle size (360+/
      2.5nm) than prepared with ultrasonication method (281+/-5.3nm). The zeta
      potential of the prepared formulations by these two methods varied from - 23.10
      +/-1.23 to -26.01 +/-0.89 mV. The maximum entrapment efficiency (62.14 +/-1.29%)
      was obtained in modified solvent injection method. The total drug content was
      nearly same (98%) in both the methods. In vitro release studies were performed in
      phosphate buffer (pH 6.8) with 0.5% sodium lauryl sulphate (SLS) using dialysis
      bag diffusion technique. The cumulative drug release was 30% and 50% within 2 hrs
      in modified solvent injection and ultrasonication method, respectively. This
      indicates that RG-SLN prepared from modified injection method released the drug
      more slowly than SLNs prepared with ultrasonication method. Differential scanning
      calorimetry indicates that repaglinide (RG) entrapped in the solid lipid
      nanoparticles (SLN) exist in an amorphous or molecular state. Repaglinide loaded
      solid lipid nanoparticles prepared with both methods were of spherical shape as
      observed by transmission electron microscopy (TEM). These results suggest that
      modified solvent injection method is more suitable for preparation of repaglinide
      SLNs using stearic acid.

PMID- 20044910
TI  - Hexosomes: a novel drug delivery system.
AB  - Polar lipids and various surfactants exhibit rich phase behavior depending on the
      composition of the lipids and the physicochemical conditions. Lamellar
      (L(alpha)), hexagonal (Inverted [H(II)]) and normal or inverted cubic
      (bicontinuous or micellar) structures are some of the most common lyotropic
      liquid crystalline phases. Hexosomes are the reverse hexagonal phases comprised
      of hexagonally close-packed infinite water layers covered by surfactants
      monolayer. Hexosomes (dispersed HII phases) due to their special structural
      properties have potential to be used as alternative delivery vehicle for
      pharmaceuticals. Biologically active molecules can either be accommodated within
      the aqueous domains or can be directly coupled to the lipid hydrophobic moieties
      oriented radially outwards from the centre of the water rods. Due to these
      special properties of hexosomes, they are used to improve solubility of poorly
      water soluble drugs and to transport therapeutic peptides and proteins by oral,
      transdermal, and parenteral routes. This article includes various methods of
      preparation of hexosomes and their application in drug delivery through various
      routes.

PMID- 20044913
TI  - Infective endocarditis.

PMID- 20044914
TI  - CD44 - a new cardiovascular drug target or merely an innocent bystander?
AB  - CD44, short for cluster of differentiation 44, is an adhesion molecule of the
      hyaluronate receptor family. Expressed on the surface of most vertebrate cells,
      it functions as a receptor for several extracellular matrix components, e.g.,
      hyaluronan, collagen, laminin, fibronectin, and osteopontin. CD44 has in recent
      years been intensively studied in connection with different forms of cancer,
      where CD44 may regulate invasiveness and tumor progression. Although major
      functions involve adhesion and migration, CD44 also affects leukocyte homing and
      recruitment, phagocytosis, matrix remodeling, proliferation, and apoptosis. As
      such, CD44 is an interesting putative molecule in cardiovascular drug therapy.
      Accumulating evidence from human studies point to CD44 as involved in
      inflammatory diseases such as atherosclerosis and human abdominal aneurysms. To
      date, several animal studies have shown that the role of CD44 in atherogenesis
      may vary depending on experimental model. In this Review, we trace CD44 and its
      potential role in the context of cardiovascular diseases by highlighting both
      human and animal studies that may help us understand; is CD44 a new
      cardiovascular drug target or merely an innocent bystander?

PMID- 20044916
TI  - New therapeutic strategies for treatment of neurodegenerative diseases.

PMID- 20044917
TI  - Fragment-based methods in drug discovery: it's the small things that matter.

PMID- 20044918
TI  - SVMCRYS: an SVM approach for the prediction of protein crystallization propensity
      from protein sequence.
AB  - X-ray crystallography is the most widely used method for protein 3-dimensional
      structure determination. Selection of target protein that can yield high quality
      crystal for X-ray crystallography is a challenging task. Prediction of protein
      crystallization propensity from sequence information is useful for the selection
      of target protein for crystallization. Recently, support vector machines have
      been widely used to solve various biological problems. In this work, we present a
      SVMCRYS method which use support vector machine to classify protein sequence into
      'amenable to crystallization' and 'resistant to crystallization'. SVMCRYS was
      trained on a dataset containing 728 sequences that gave diffraction quality
      crystal and 728 sequences where work had been stopped before obtaining crystal.
      The performance of SVMCRYS method was compared with other sequence-based
      crystallization prediction methods such as SECRET, CRYSTALP, OB-Score, ParCrys
      and XtalPred using three different datasets. SVMCRYS achieved better prediction
      rate with higher sensitivity and specificity. Our analysis suggests that SVMCRYS
      can be used to predict proteins which are amenable to crystallization and
      proteins which are difficult for crystallization. The SVMCRYS software, dataset
      and feature set can be obtained from
      http://www3.ntu.edu.sg/home/EPNSugan/index_files/svmcrys.htm.

PMID- 20044919
TI  - IgE-binding epitope analysis of Bla g 5, the German cockroach allergen.
AB  - Cockroach infestations have been linked with allergic diseases such as asthma in
      humans. Bla g 5, sigma class glutathione S-transferase (GST), is the major
      cockroach allergen which has the highest IgE response value of all cockroach
      allergens. Although several cockroach allergens have been identified and cloned,
      information regarding their B ell and T cell IgE-binding epitopes is limited. In
      order to analyze the IgE binding epitopes of Bla g 5, full-length and five
      peptide fragments (A, 1-100 amino acid residue; B, 91-200; Ba, 1-125; Bb, 1-150;
      Bc, 1-175) were expressed. Twelve (37.5%) of 32 sera from cockroach-sensitized
      subjects showed positive IgE reactivity to the recombinant Bla g 5 (rBla g 5).
      Six strong positive sera were selected for the epitope study. Recombinant
      proteins not containing 176-200 amino acid residues were unable to react to sera
      from cockroach sensitized individuals, suggesting that this region contains the
      IgE-binding epitope. Despite strong IgE reactivity to rBla g 5, the pooled serum
      from 5 cockroach-sensitized patients did not show IgE reactivity to all synthetic
      peptides consisting of 15 residues covering 161-200 amino acids. These results
      suggest the possibility that Bla g 5 may have a conformational epitope in the C
      terminal region. GST is the important target for the development of vaccines and
      drugs against allergic diseases because of high cross-reactivity among insect
      species. This study will aid recombinant allergen research for immunotherapy of
      cockroach allergens and other insect allergens.

PMID- 20044920
TI  - A storage protein-like Trypsin inhibitor from the Moth Bean (Phaseolus
      acutifolius) with antiproliferative activity toward lymphoma cells.
AB  - A 26-kDa trypsin inhibitor with an N-terminal sequence resembling storage
      proteins was purified from moth beans (Phaseolus acutifolius). It dose
      dependently inhibited trypsin with an IC(50) value of about 0.38 microM. It
      inhibited [methyl-(3)H] thymidine incorporation by lymphoma MBL2 cells with an
      IC(50) value of 20 microM.

PMID- 20044921
TI  - Cloning and characterization of an exo-xylogucanase from rumenal microbial
      metagenome.
AB  - A novel exo-glucanase gene (xeg5B) was isolated from a rumenal microbial
      metagenome, cloned, and expressed in E. coli. The 1548 bp gene coded for a
      protein of 516 amino acids, which assumed an (a/b)(8) fold typical of glycoside
      hydrolase (GH) family 5. The protein molecule consisted of a loop segment
      blocking one end of the active site, which potentially provided the enzyme with
      exo-acting property. The recombinant enzyme showed exclusive specificity towards
      only xyloglucan and oligoxyloglucan substrates with no detectable activity on
      unsubstituted linear glucans, CMC, laminarin, and lichenan. The major end
      products of exhaustive hydrolysis were XX (tetrasaccharide) and XG
      (trisaccharide). The hydrolysis of tamarind xyloglucan followed the Michaelis
      Menten kinetics, yielding K(m) and V(max) of 2.12+/-0.13 mg/ml and 0.17+/-0.01
      mg/ml/min (37 degrees C, pH 6.0), respectively.

PMID- 20044922
TI  - Identifying the hierarchy of dynamic domains in proteins using the data of
      molecular dynamics simulations.
AB  - The Hierarchical Domain-Wise Alignment (HDWA) technique of domain identification
      in proteins is presented. HDWA is designed to identify hierarchically organized
      dynamic domains in proteins using the MD trajectories by eliminating systematic
      motions from MD trajectories recursively in a model-free manner. The method is
      tested on the proteins from different structural classes.

PMID- 20044923
TI  - Antibodies against recombinant shiga toxin subunit B neutralize shiga toxin
      toxicity in HeLa cells.
AB  - Shigella dysenteriae type 1 and Escherichia coli O157:H7 produce Shiga toxin 1
      (Stx) and Shiga toxin1 (Stx1), respectively and these two toxins are almost
      identical. E. coli O157:H7 is the major cause of diarrhea-associated hemolytic
      uremic syndrome. Stx and Stx1 are AB5 type of toxin with a molecular weight of 70
      kDa, comprising an enzymaticaly-active A subunit (32 kDa) and five receptor
      binding B subunits (7.7 kDa). In this study DNA fragment (289 bp, Gene Bank Accn
      No. EF685161) coding for B chain of Stx was amplified from S. dysenteriae type1
      and cloned. Shiga toxin-binding subunit was expressed and purified in native
      conditions by affinity and gel permeation chromatography with the yield of 5.1
      mg/L in shake flask culture. For the purpose of immunization, the polypeptide was
      polymerized with glutaraldehyde. Hyper immune serum produced in mice reacted with
      the purified polypeptide and intact Shiga toxin. The anti-StxB antiserum
      effectively neutralized the cytotoxicity of Shiga toxin towards HeLa cells.

PMID- 20044924
TI  - Drastic effects on fibril formation of amyloid-beta peptides by the addition of
      amino acid residue units to the termini.
AB  - We report that the addition of amino acids to the amyloid peptide dramatically
      affected the structure and the rate of formation of amyloid fibrils. The
      attachment of three lysines to Abeta(10-35) gave the formation of remarkably long
      fibrils, while three glutamates resulted in a faster formation rate of the
      fibrils.

PMID- 20044925
TI  - Effects of nursing education on the image of nursing as a profession in Israel.
AB  - The purpose of this study was to examine the perceptions of nursing students in
      Israel regarding nursing as a profession and nurses' public image, and whether
      there is a difference between the perceptions of first-year and more advanced
      nursing students. A questionnaire based on the work of Tzeng (2006) was
      administered to 200 first-year nursing students and 200 more advanced students.
      Most of the students felt the nursing profession needs to undergo an image
      change, while first-year students perceived nurses as more angelic and romantic
      than more advanced students. A positive correlation was found between
      satisfaction with nurses in the field and the image of nursing. In order to
      reinforce a positive image of nursing as a career, nurse educators should alter
      negative stereotypes about the profession.

PMID- 20044926
TI  - Sense and nonsense from a systems biology approach to microbial recombinant
      protein production.
AB  - The 'Holy Grail' of recombinant protein production remains the availability of
      generic protocols and hosts for the production of even the most difficult target
      products. The present review provides first an explanation why the shock imposed
      on bacteria using a standard induction protocol not only arrests growth, but also
      decreases the number of colony-forming units by several orders of magnitude.
      Particular emphasis is placed on findings of numerous genome-wide transcriptomic
      studies that highlight cellular stress, in which the general stress, heat-shock
      and stringent responses are the underlying basis for the manifestation of the
      deterioration of cell physiology. We then review common approaches used to solve
      bottlenecks in protein folding and post-translational modification that result in
      recombinant protein deposition in cytoplasmic inclusion bodies. Finally, we
      suggest a generic approach to process design that minimizes stress on the
      production host and a strategy for isolating improved hosts.

PMID- 20044927
TI  - Preoperative scallop-by-scallop assessment of mitral prolapse using 2D
      transthoracic echocardiography.
AB  - BACKGROUND: This study was conducted to assess the accuracy of harmonic imaging
      2D-transthoracic echocardiography (2D-TTE) segmental analysis compared to
      surgical findings, in degenerative mitral regurgitation (MR). METHODS: Seventy
      seven consecutive patients with severe degenerative MR were prospectively
      enrolled. Preoperative 2D-TTE with precise localization of prolapsing or flailing
      scallops/segments was performed. All patients underwent mitral valve surgical
      repair. Surgical reports (SR), including valve description, were used as
      references for comparisons. A postoperative control 2D-TTE was performed.
      RESULTS: Out of 462 scallops/segments studied, surgical inspection identified 102
      prolapses or flails (22%), 92 of which had previously been detected by 2D-TTE
      (90.2% sensitivity, 100% specificity). Agreement between preoperative 2D-TTE
      segmental analysis and SR was 97.8% (k = 0.93; p < 0.0001). Sixty-nine out of 77
      2D-TTE reports were completely concordant with SR (89.6% diagnostic accuracy).
      None of the 8 non-concordant 2D-TTE reports were in complete disagreement with
      SR. P2 scallop was always involved in posterior leaflet prolapse or flail and was
      described correctly by 2D-TTE in 68 out of 69 patients (98,7% agreement, k =
      0,93; 98.5% sensitivity). The anterior leaflet was involved in 14 patients (18%);
      A2 segment was involved in all of those cases and was correctly detected by 2D
      TTE in 13 (98,7% agreement, k = 0,95; 92,8% sensitivity). Antero-lateral and
      postero-medial para-commissural prolapse or flail had a lower prevalence (14% and
      10% respectively), with 2D-TTE sensitivity respectively of 64% and 50%.
      CONCLUSIONS: 2D-TTE, performed by an experienced echo-lab, has very good
      diagnostic accuracy in localizing the scallops/segments involved in degenerative
      MR, particularly for the middle ones (P2-A2), which represent almost the totality
      of prolapses. More invasive, time consuming and expensive exams should be
      reserved to selected cases.

PMID- 20044928
TI  - Mutation screen and association studies for the fatty acid amide hydrolase (FAAH)
      gene and early onset and adult obesity.
AB  - BACKGROUND: The orexigenic effects of cannabinoids are limited by activation of
      the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim
      of this study was to analyse whether FAAH alleles are associated with early and
      late onset obesity. METHODS: We initially assessed association of five single
      nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to
      521 German obese children and both parents. SNPs with nominal p-values <or= 0.1
      were subsequently analysed in 235 independent German obesity families. SNPs
      associated with childhood obesity (p-values <or2= 0.05) were further analysed in
      8,491 adult individuals of a population-based cohort (KORA) for association with
      adult obesity. One SNP was further analysed in 985 German obese adults and 588
      normal and underweight controls. In parallel, we screened the FAAH coding region
      for novel sequence variants in 92 extremely obese children using single-stranded
      conformation-polymorphism-analysis and denaturing HPLC and assessed the
      implication of the identified new variants for childhood obesity. RESULTS: The
      trio analysis revealed some evidence for an association of three SNPs in FAAH
      (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values
      between 0.06 and 0.10). Although analyses of these variants in 235 independent
      obesity families did not result in statistically significant effects (two-sided p
      values between 0.14 and 0.75), the combined analysis of all 603 obesity families
      supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632)
      with early onset extreme obesity (p-values between 0.02 and 0.03). No association
      was, however, found between these variants and adult obesity. The mutation screen
      revealed four novel variants, which were not associated with early onset obesity
      (p > 0.05). CONCLUSIONS: As we observed some evidence for an association of the
      FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we
      conclude that the FAAH variants analyzed here at least do not seem to play a
      major role in the etiology of obesity within our samples.

PMID- 20044929
TI  - Women's evaluation of abuse and violence care in general practice: a cluster
      randomised controlled trial (weave).
AB  - BACKGROUND: Intimate partner abuse (IPA) is a major public health problem with
      serious implications for the physical and psychosocial wellbeing of women,
      particularly women of child-bearing age. It is a common, hidden problem in
      general practice and has been under-researched in this setting. Opportunities for
      early intervention and support in primary care need to be investigated given the
      frequency of contact women have with general practice. Despite the high
      prevalence and health consequences of abuse, there is insufficient evidence for
      screening in primary care settings. Furthermore, there is little rigorous
      evidence to guide general practitioners (GPs) in responding to women identified
      as experiencing partner abuse. This paper describes the design of a trial of a
      general practice-based intervention consisting of screening for fear of partner
      with feedback to GPs, training for GPs, brief counselling for women and minimal
      practice organisational change. It examines the effect on women's quality of
      life, mental health and safety behaviours. METHODS/DESIGN: weave is a cluster
      randomised controlled trial involving 40 general practices in Victoria,
      Australia. Approximately 500 women (16-50 years) seen by the GP in the previous
      year are mailed a short lifestyle survey containing an item to screen for IPA.
      Women who indicate that they were afraid of a partner/ex-partner in the last year
      and provide contact details are invited to participate. Once baseline data are
      collected, GPs are randomly assigned to either a group involving healthy
      relationship and responding to IPA training plus inviting women for up to 6
      sessions of counselling or to a group involving basic education and usual care
      for women. Outcomes will be evaluated by postal survey at 6 and 12 months
      following delivery of the intervention. There will be an economic evaluation, and
      process evaluation involving interviews with women and GPs, to inform
      understanding about implementation and outcomes. DISCUSSION: The weave trial
      responds to an urgent need for more evidence on what can be achieved in primary
      care with regard to responding to women who experience IPA. It will provide
      important knowledge about the effectiveness of a brief method of screening,
      professional IPA training program and brief counselling for women. TRIAL
      REGISTRATION: [ACTRN12608000032358].

PMID- 20044930
TI  - High frequency of SEN virus infection in thalassemic patients and healthy blood
      donors in Iran.
AB  - BACKGROUND: SEN virus is a blood-borne, circular ssDNA virus and possessing nine
      genotypes (A to I). Among nine genotypes, SENV-D and SENV-H genotypes have the
      strong link with patients with unknown (none-A to E) hepatitis infections.
      Infection with blood-borne viruses is the second important cause of death in
      thalassemic patients. The aim of this study was to determine the frequency of
      SENV-D and SENV-H genotypes viremia by performing nested-PCR in 120 and 100 sera
      from healthy blood donors and thalassemic patients in Guilan Province, North of
      Iran respectively. Also, to explicate a possible role of SEN virus in liver
      disease and established changes in blood factors, the serum aminotransferases
      (ALT and AST) and some of the blood factors were measured. RESULTS: Frequency of
      SENV-D, SENV (SENV-H or SENV-D) and co-infection (both SENV-D and SENV-H) viremia
      was significantly higher among thalassemic patients than healthy individuals.
      Frequency of SENV-H viremia was significantly higher than SENV-D among healthy
      individuals. In comparison to SENV-D negative patients, the mean of mean
      corpuscular hemoglobin was significantly higher in SENV-D positive and co
      infection cases (P < 0.05). The means of AST and ALT were significantly higher in
      thalassemic patients than healthy blood donors, but there were not any
      significant differences in the means of the liver levels between SENV-positive
      and -negative individuals in healthy blood donors and thalassemic patients. High
      nucleotide homology observed among PCR amplicon's sequences in healthy blood
      donors and thalassemic patients. CONCLUSIONS: The high rate of co-infection shows
      that different genotypes of SENV have no negative effects on each other. The high
      frequency of SENV infection among thalassemic patients suggests blood transfusion
      as main route of transmission. High frequency of SENV infection in healthy
      individuals indicates that other routes rather than blood transfusion also are
      important. Frequency of 90.8% of SENV infection among healthy blood donors as
      well as high nucleotide homology of sequenced amplicons between two groups can
      probably suggest that healthy blood donors infected by SENV act partly as a
      source of SENV transmission to the thalassemic patients. In conclusion, SENV-D
      isolate in Guilan Province may be having a pathogenic agent for thalassemic
      patients.

PMID- 20044931
TI  - Function of nuclear transport factor 2 and Ran in the 20E signal transduction
      pathway in the cotton bollworm, Helicoverpa armigera.
AB  - BACKGROUND: Nuclear transport factor 2 and small GTPase Ran participate in the
      nucleo-cytoplasm transport of macromolecules, but their function in the 20
      hydroxyecdysone (20E) signal transduction pathway are not well known. RESULTS: A
      703 bp encoding Ntf2 and a 1233 bp encoding Ran full-length cDNAs were cloned
      from Helicoverpa armigera, and named Ha-Ntf2 and Ha-Ran, respectively. Northern
      blot and immunoblotting revealed that Ha-Ntf2 had an obviously higher expression
      levels in the head-thorax and integument of the metamorphically committed larvae.
      In contrast, the expression of Ha-Ran did not show obvious variation at various
      developmental stages in four tissues by immunoblotting analysis, except in the
      midgut, which showed increased expression from 5th-36 h (molting) to 6th-48 h.
      Both expressions of Ha-Ntf2 and Ha-Ran could be upregulated by 20E in vitro.
      Immunohistochemistry revealed that Ha-Ntf2 and Ha-Ran were primarily localized in
      the nucleus of various tissues. Protein binding assay and co-immunoprecipitation
      indicated that Ha-Ntf2 and Ha-Ran can combine with each other in vitro and in
      vivo. Knock down of Ha-Ntf2 or Ha-Ran by RNAi resulted in the suppression of
      other 20E regulated genes including EcR-B1, USP1, E75B, BR-CZ2, HHR3 and Ha
      eIF5c. In addition, the knockdown of Ha-Ntf2 resulted in Ha-Ran being prevented
      in the cytoplasm. The nuclear location of the ecdysone receptor b1 (EcR-B1) was
      also blocked after the knockdown of Ha-Ntf2 and Ha-Ran. CONCLUSION: These
      evidences suggested that Ha-Ntf2 and Ha-Ran participated in the 20E signal
      transduction pathway by regulating the location of EcR-B1.

PMID- 20044932
TI  - The association of spinal osteoarthritis with lumbar lordosis.
AB  - BACKGROUND: Careful review of published evidence has led to the postulate that
      the degree of lumbar lordosis may possibly influence the development and
      progression of spinal osteoarthritis, just as misalignment does in other joints.
      Spinal degeneration can ensue from the asymmetrical distribution of loads. The
      resultant lesions lead to a domino- like breakdown of the normal morphology,
      degenerative instability and deviation from the correct configuration. The aim of
      this study is to investigate whether a relationship exists between the sagittal
      alignment of the lumbar spine, as it is expressed by lordosis, and the presence
      of radiographic osteoarthritis. METHODS: 112 female subjects, aged 40-72 years,
      were examined in the Outpatients Department of the Orthopedics' Clinic,
      University Hospital of Heraklion, Crete. Lumbar radiographs were examined on two
      separate occasions, independently, by two of the authors for the presence of
      osteoarthritis. Lordosis was measured from the top of L1 to the bottom of L5 as
      well as from the top of L1 to the top of S1. Furthermore, the angle between the
      bottom of L5 to the top of S1 was also measured. RESULTS AND DISCUSSION: 49 women
      were diagnosed with radiographic osteoarthritis of the lumbar spine, while 63
      women had no evidence of osteoarthritis and served as controls. The two groups
      were matched for age and body build, as it is expressed by BMI. No statistically
      significant differences were found in the lordotic angles between the two groups
      CONCLUSIONS: There is no difference in lordosis between those affected with
      lumbar spine osteoarthritis and those who are disease free. It appears that
      osteoarthritis is not associated with the degree of lumbar lordosis.

PMID- 20044933
TI  - Predicting gene function using hierarchical multi-label decision tree ensembles.
AB  - BACKGROUND: S. cerevisiae, A. thaliana and M. musculus are well-studied organisms
      in biology and the sequencing of their genomes was completed many years ago. It
      is still a challenge, however, to develop methods that assign biological
      functions to the ORFs in these genomes automatically. Different machine learning
      methods have been proposed to this end, but it remains unclear which method is to
      be preferred in terms of predictive performance, efficiency and usability.
      RESULTS: We study the use of decision tree based models for predicting the
      multiple functions of ORFs. First, we describe an algorithm for learning
      hierarchical multi-label decision trees. These can simultaneously predict all the
      functions of an ORF, while respecting a given hierarchy of gene functions (such
      as FunCat or GO). We present new results obtained with this algorithm, showing
      that the trees found by it exhibit clearly better predictive performance than the
      trees found by previously described methods. Nevertheless, the predictive
      performance of individual trees is lower than that of some recently proposed
      statistical learning methods. We show that ensembles of such trees are more
      accurate than single trees and are competitive with state-of-the-art statistical
      learning and functional linkage methods. Moreover, the ensemble method is
      computationally efficient and easy to use. CONCLUSIONS: Our results suggest that
      decision tree based methods are a state-of-the-art, efficient and easy-to-use
      approach to ORF function prediction.

PMID- 20044934
TI  - Genome size differentiates co-occurring populations of the planktonic diatom
      Ditylum brightwellii (Bacillariophyta).
AB  - BACKGROUND: Diatoms are one of the most species-rich groups of eukaryotic
      microbes known. Diatoms are also the only group of eukaryotic micro-algae with a
      diplontic life history, suggesting that the ancestral diatom switched to a life
      history dominated by a duplicated genome. A key mechanism of speciation among
      diatoms could be a propensity for additional stable genome duplications. Across
      eukaryotic taxa, genome size is directly correlated to cell size and inversely
      correlated to physiological rates. Differences in relative genome size, cell
      size, and acclimated growth rates were analyzed in isolates of the diatom Ditylum
      brightwellii. Ditylum brightwellii consists of two main populations with
      identical 18s rDNA sequences; one population is distributed globally at temperate
      latitudes and the second appears to be localized to the Pacific Northwest coast
      of the USA. These two populations co-occur within the Puget Sound estuary of WA,
      USA, although their peak abundances differ depending on local conditions.
      RESULTS: All isolates from the more regionally-localized population (population
      2) possessed 1.94 +/- 0.74 times the amount of DNA, grew more slowly, and were
      generally larger than isolates from the more globally distributed population
      (population 1). The ITS1 sequences, cell sizes, and genome sizes of isolates from
      New Zealand were the same as population 1 isolates from Puget Sound, but their
      growth rates were within the range of the slower-growing population 2 isolates.
      Importantly, the observed genome size difference between isolates from the two
      populations was stable regardless of time in culture or the changes in cell size
      that accompany the diatom life history. CONCLUSIONS: The observed two-fold
      difference in genome size between the D. brightwellii populations suggests that
      whole genome duplication occurred within cells of population 1 ultimately giving
      rise to population 2 cells. The apparent regional localization of population 2 is
      consistent with a recent divergence between the populations, which are likely
      cryptic species. Genome size variation is known to occur in other diatom genera;
      we hypothesize that genome duplication may be an active and important mechanism
      of genetic and physiological diversification and speciation in diatoms.

PMID- 20044935
TI  - Species distribution and susceptibility profile of Candida species in a Brazilian
      public tertiary hospital.
AB  - BACKGROUND: Species identification and antifungal susceptibility tests were
      carried out on 212 Candida isolates obtained from bloodstream infections, urinary
      tract infections and dialysis-associated peritonitis, from cases attended at a
      Brazilian public tertiary hospital from January 1998 to January 2005. FINDINGS:
      Candida albicans represented 33% of the isolates, Candida parapsilosis 31.1%,
      Candida tropicalis 17.9%,Candida glabrata 11.8%, and others species 6.2%. In
      blood culture, C. parapsilosis was the most frequently encountered species (48%).
      The resistance levels to the antifungal azoles were relatively low for the
      several species, except for C. tropicalis and C. glabrata. Amphotericin B
      resistance was observed in 1 isolate of C. parapsilosis. CONCLUSIONS: The species
      distribution and antifungal susceptibility herein observed presented several
      epidemiological features common to other tertiary hospitals in Latin American
      countries. It also exhibited some peculiarity, such as a very high frequency of
      C. parapsilosis both in bloodstream infections and dialysis-associated
      peritonitis. C. albicans also occurred in an important number of case infections,
      in all evaluated clinical sources. C. glabrata presented a high proportion of
      resistant isolates. The data emphasize the necessity to carry out the correct
      species identification accompanied by the susceptibility tests in all tertiary
      hospitals.

PMID- 20044936
TI  - Bacteremia causes hippocampal apoptosis in experimental pneumococcal meningitis.
AB  - BACKGROUND: Bacteremia and systemic complications both play important roles in
      brain pathophysiological alterations and the outcome of pneumococcal meningitis.
      Their individual contributions to the development of brain damage, however, still
      remain to be defined. METHODS: Using an adult rat pneumococcal meningitis model,
      the impact of bacteremia accompanying meningitis on the development of
      hippocampal injury was studied. The study comprised of the three groups: I.
      Meningitis (n = 11), II. meningitis with attenuated bacteremia resulting from iv
      injection of serotype-specific pneumococcal antibodies (n = 14), and III.
      uninfected controls (n = 6). RESULTS: Pneumococcal meningitis resulted in a
      significantly higher apoptosis score 0.22 (0.18-0.35) compared to uninfected
      controls (0.02 (0.00-0.02), Mann Whitney test, P = 0.0003). Also, meningitis with
      an attenuation of bacteremia by antibody treatment resulted in significantly
      reduced apoptosis (0.08 (0.02-0.20), P = 0.01) as compared to meningitis.
      CONCLUSIONS: Our results demonstrate that bacteremia accompanying meningitis
      plays an important role in the development of hippocampal injury in pneumococcal
      meningitis.

PMID- 20044937
TI  - Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP
      dependent kinase--Pi-dependent pyrophosphorylase from bacteria.
AB  - BACKGROUND: Phosphoenolpyruvate synthetase (PEPS; EC 2.7.9.2) catalyzes the
      synthesis of phosphoenolpyruvate from pyruvate in Escherichia coli when cells are
      grown on a three carbon source. It also catalyses the anabolic conversion of
      pyruvate to phosphoenolpyruvate in gluconeogenesis. A bioinformatics search
      conducted following the successful cloning and expression of maize leaf pyruvate,
      orthophosphate dikinase regulatory protein (PDRP) revealed the presence of PDRP
      homologs in more than 300 bacterial species; the PDRP homolog was identified as
      DUF299. RESULTS: This paper describes the cloning and expression of both PEPS and
      DUF299 from E. coli and establishes that E. coli DUF299 catalyzes both the ADP
      dependent inactivation and the Pi-dependent activation of PEPS. CONCLUSION: This
      paper represents the first report of a bifunctional regulatory enzyme catalysing
      an ADP-dependent phosphorylation and a Pi-dependent pyrophosphorylation reaction
      in bacteria.

PMID- 20044939
TI  - Paving Pathways: shaping the Public Health workforce through tertiary education.
AB  - Public health educational pathways in Australia have traditionally been the
      province of Universities, with the Master of Public Health (MPH) recognised as
      the flagship professional entry program. Public health education also occurs
      within the fellowship training of the Faculty of Public Health Medicine, but
      within Australia this remains confined to medical graduates. In recent years,
      however, we have seen a proliferation of undergraduate degrees as well as an
      increasing public health presence in the Vocational Education and Training (VET)
      sector.Following the 2007 Australian Federal election, the new Labour government
      brought with it a refreshing commitment to a more inclusive and strategic style
      of government. An important example of this was the 2020 visioning process that
      identified key issues of public health concern, including an acknowledgment that
      it was unacceptable to allocate less than 2% of the health budget towards disease
      prevention. This led to the recommendation for the establishment of a national
      preventive health agency (Australia: the healthiest country by 2020 National
      Preventative Health Strategy, Prepared by the Preventative Health Taskforce
      2009).The focus on disease prevention places a spotlight on the workforce that
      will be required to deliver the new investment in health prevention, and also on
      the role of public health education in developing and upskilling the workforce.
      It is therefore timely to reflect on trends, challenges and opportunities from a
      tertiary sector perspective. Is it more desirable to focus education efforts on
      selected lead issues such as the "obesity epidemic", climate change, Indigenous
      health and so on, or on the underlying theory and skills that build a flexible
      workforce capable of responding to a range of health challenges? Or should we
      aspire to both?This paper presents some of the key discussion points from 2008 -
      2009 of the Public Health Educational Pathways workshops and working group of the
      Australian Network of Public Health Institutions. We highlight some of the
      competing tensions in public health tertiary education, their impact on public
      health training programs, and the educational pathways that are needed to grow,
      shape and prepare the public health workforce for future challenges.

PMID- 20044938
TI  - Representations and coverage of non-English-speaking immigrants and multicultural
      issues in three major Australian health care publications.
AB  - BACKGROUND: No recent Australian studies or literature, provide evidence of the
      extent of coverage of multicultural health issues in Australian healthcare
      research. A series of systematic literature reviews in three major Australian
      healthcare journals were undertaken to discover the level, content, coverage and
      overall quality of research on multicultural health. Australian healthcare
      journals selected for the study were The Medical Journal of Australia (MJA), The
      Australian Health Review (AHR), and The Australian and New Zealand Journal of
      Public Health (ANZPH). Reviews were undertaken of the last twelve (12) years
      (1996-August 2008) of journal articles using six standard search terms: 'non
      English-speaking', 'ethnic', 'migrant', 'immigrant', 'refugee' and
      'multicultural'. RESULTS: In total there were 4,146 articles published in these
      journals over the 12-year period. A total of 90 or 2.2% of the total articles
      were articles primarily based on multicultural issues. A further 62 articles
      contained a major or a moderate level of consideration of multicultural issues,
      and 107 had a minor mention. CONCLUSIONS: The quantum and range of multicultural
      health research and evidence required for equity in policy, services,
      interventions and implementation is limited and uneven. Most of the original
      multicultural health research articles focused on newly arrived refugees, asylum
      seekers, Vietnamese or South East Asian communities. While there is some seminal
      research in respect of these represented groups, there are other communities and
      health issues that are essentially invisible or unrepresented in research. The
      limited coverage and representation of multicultural populations in research
      studies has implications for evidence-based health and human services policy.

PMID- 20044940
TI  - Framing access to medicines in developing countries: an analysis of media
      coverage of Canada's Access to Medicines Regime.
AB  - BACKGROUND: In September 2003, the Canadian government committed to developing
      legislation that would facilitate greater access to affordable medicines for
      developing countries. Over the course of eight months, the legislation, now known
      as Canada's Access to Medicines Regime (CAMR), went through a controversial
      policy development process and the newspaper media was one of the major venues in
      which the policy debates took place. The purpose of this study was to examine how
      the media framed CAMR to determine how policy goals were conceptualized, which
      stakeholder interests controlled the public debate and how these variables
      related to the public policy process. METHODS: We conducted a qualitative content
      analysis of newspaper coverage of the CAMR policy and implementation process from
      2003-2008. The primary theoretical framework for this study was framing theory. A
      total of 90 articles from 11 Canadian newspapers were selected for inclusion in
      our analysis. A team of four researchers coded the articles for themes relating
      to access to medicines and which stakeholders' voice figured more prominently on
      each issue. Stakeholders examined included: the research-based industry, the
      generic industry, civil society, the Canadian government, and developing country
      representatives. RESULTS: The most frequently mentioned themes across all
      documents were the issues of drug affordability, intellectual property, trade
      agreements and obligations, and development. Issues such as human rights,
      pharmaceutical innovation, and economic competitiveness got little media
      representation. Civil society dominated the media contents, followed far behind
      by the Canadian government, the research-based and generic pharmaceutical
      industries. Developing country representatives were hardly represented in the
      media. CONCLUSIONS: Media framing obscured the discussion of some of the
      underlying policy goals in this case and failed to highlight issues which are now
      significant barriers to the use of the legislation. Using the media to engage the
      public in more in-depth exploration of the policy issues at stake may contribute
      to a more informed policy development process. The media can be an effective
      channel for those stakeholders with a weaker voice in policy deliberations to
      raise public attention to particular issues; however, the political and
      institutional context must be taken into account as it may outweigh media framing
      effects.

PMID- 20044941
TI  - Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in
      mice.
AB  - BACKGROUND: The aim of this study is to examine the safety and distribution of Ad
      EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1),
      in the mice colon carcinoma model. METHODS: After bone marrow cells (BMCs) were
      infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone
      marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus
      neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was
      detected by in situ hybridization and immunohistochemistry. The peripheral
      hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and
      platelet (Plt) counts were analyzed. RESULTS: Neither total adenovirus antibody
      nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry
      demonstrated concordant expression of human MDR1 and P-gp which were found in
      lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen,
      brain and tumor. No significant abnormality of the recovery hematocyte was
      observed on Day 30 after treatment. CONCLUSION: The results indicate that IBM-BMT
      administration of a replication defective adenovirus is a feasible mode of
      delivery, allowing exogenous transference. The findings in this study are
      conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

PMID- 20044942
TI  - Plasmodium infection and its risk factors in eastern Uganda.
AB  - BACKGROUND: Malaria is a leading cause of disease burden in Uganda, although
      surprisingly few contemporary, age-stratified data exist on malaria epidemiology
      in the country. This report presents results from a total population survey of
      malaria infection and intervention coverage in a rural area of eastern Uganda,
      with a specific focus on how risk factors differ between demographic groups in
      this population. METHODS: In 2008, a cross-sectional survey was conducted in four
      contiguous villages in Mulanda, sub-county in Tororo district, eastern Uganda, to
      investigate the epidemiology and risk factors of Plasmodium species infection.
      All permanent residents were invited to participate, with blood smears collected
      from 1,844 individuals aged between six months and 88 years (representing 78% of
      the population). Demographic, household and socio-economic characteristics were
      combined with environmental data using a Geographical Information System.
      Hierarchical models were used to explore patterns of malaria infection and
      identify individual, household and environmental risk factors. RESULTS: Overall,
      709 individuals were infected with Plasmodium, with prevalence highest among 5-9
      year olds (63.5%). Thin films from a random sample of 20% of parasite positive
      participants showed that 94.0% of infections were Plasmodium falciparum and 6.0%
      were P. malariae; no other species or mixed infections were seen. In total, 68%
      of households owned at least one mosquito although only 27% of school-aged
      children reported sleeping under a net the previous night. In multivariate
      analysis, infection risk was highest amongst children aged 5-9 years and remained
      high in older children. Risk of infection was lower for those that reported
      sleeping under a bed net the previous night and living more than 750 m from a
      rice-growing area. After accounting for clustering within compounds, there was no
      evidence for an association between infection prevalence and socio-economic
      status, and no evidence for spatial clustering. CONCLUSION: These findings
      demonstrate that mosquito net usage remains inadequate and is strongly associated
      with risk of malaria among school-aged children. Infection risk amongst adults is
      influenced by proximity to potential mosquito breeding grounds. Taken together,
      these findings emphasize the importance of increasing net coverage, especially
      among school-aged children.

PMID- 20044943
TI  - Implementation of uniform information on fetal movement in a Norwegian population
      reduced delayed reporting of decreased fetal movement and stillbirths in
      primiparous women - a clinical quality improvement.
AB  - BACKGROUND: Delayed maternal reporting of decreased fetal movement (DFM) is
      associated with adverse pregnancy outcomes. Inconsistent information on fetal
      activity to women during the antenatal period may result in delayed reporting of
      DFM. We aimed to evaluate an intervention of implementation of uniform
      information on fetal activity to women during the antenatal period. METHODS: In a
      prospective before-and-after study, singleton women presenting DFM in the third
      trimester across 14 hospitals in Norway were registered. Outcome measures were
      maternal behavior regarding reporting of DFM, concerns and stillbirth. In
      addition, cross-sectional studies of all women giving birth were undertaken to
      assess maternal concerns about fetal activity, and population-based data were
      obtained from the Medical Birth Registry Norway. RESULTS: Pre- and post
      intervention cohorts included 19 407 and 46 143 births with 1 215 and 3 038 women
      with DFM respectively. Among primiparous women with DFM, a reduction in delayed
      reporting of DFM (>/=48 hrs) OR 0.61 (95% CI 0.47-0.81) and stillbirths OR 0.36
      (95% CI 0.19-0.69) was shown in the post-intervention period. No difference was
      shown in rates of consultations for DFM or maternal concerns. Stillbirth rates
      and maternal behavior among women who were of non-Western origin, smokers,
      overweight or >34 years old were unchanged. CONCLUSIONS: Uniform information on
      fetal activity provided to pregnant women was associated with a reduction in the
      number of primiparous women who delayed reporting of DFM and a reduction of the
      stillbirth rates for primiparous women reporting DFM. The information did not
      appear to increase maternal concerns or rate of consultation. Due to different
      imperfections in different clinical settings, further studies in other
      populations replicating these findings are required.

PMID- 20044944
TI  - The prevalence and functional impact of musculoskeletal conditions amongst
      clients of a primary health care facility in an under-resourced area of Cape
      Town.
AB  - BACKGROUND: The extent of disease burden of musculoskeletal conditions (MSC) not
      due to injury has not been well determined in sub-Saharan Africa. The 1999 Global
      Burden of Disease study estimated the prevalence of osteoarthritis and rheumatoid
      arthritis to be 150/100,000 compared to 1,500/100,000 in Europe. The objective of
      the study was to determine the prevalence of MSC and the functional implications
      in a sample of people attending community health centres in Cape Town, South
      Africa. METHODS: A cross-sectional, descriptive study was conducted in clinics in
      two resource poor communities. Phase I consisted of screening and those who
      screened positive for peripheral or spinal joint pain went on to complete Phase
      II, which included the Stanford Health Assessment Questionnaire. RESULTS: 1005
      people were screened in Phase I. Of these, 362 (36%) reported MSC not due to
      injury in the past three months. Those with MSC had higher rates of co
      morbidities in every category than those without. The mean Disability Index for
      those with MSC was mild to moderate and moderate to severe in those over 55
      years. CONCLUSIONS: Although the sample may not be representative of the general
      community, the prevalence is considerably greater than those reported elsewhere
      even when the population of the catchment area is used as a denominator, (367/100
      000). The common presentation of MSC with co-morbid diabetes and hypertension
      requires holistic management by appropriately trained health care practitioners.
      Any new determination of burden of disease due to MSC should recognise that these
      disorders may be more prevalent in developing countries than previously
      estimated.

PMID- 20044947
TI  - Periplasmic glucans isolated from Proteobacteria.
AB  - Periplasmic glucans (PGs) are general constituents in the periplasmic space of
      Proteobacteria. PGs from bacterial strains are found in larger amounts during
      growth on medium with low osmolarity and thus are often been specified as
      osmoregulated periplasmic glucans (OPGs). Furthermore, they appear to play
      crucial roles in pathogenesis and symbiosis. PGs have been classified into four
      families based on the structural features of their backbones, and they can be
      modified by a variety of non-sugar substituents. It has also recently been
      confirmed that novel PGs with various degrees of polymerization (DPs) and/or
      different substituents are produced under different growth conditions among
      Proteobacteria. In addition to their biological functions as regulators of low
      osmolarity, PGs have a variety of physico-chemical properties due to their
      inherent three-dimensional structures, hydrogen-bonding and complex-forming
      abilities. Thus, much attention has recently been focused on their physico
      chemical applications. In this review, we provide an updated classification of
      PGs, as well as a description of the occurrences of novel PGs with substituents
      under various bacterial growth environments, the genes involved in PG
      biosynthesis and the various physico-chemical properties of PGs.

PMID- 20044945
TI  - Unwanted incidents during transition of geriatric patients from hospital to home:
      a prospective observational study.
AB  - BACKGROUND: Geriatric patients recently discharged from hospital experience
      increased chance of unplanned readmissions and admission to nursing homes.
      Several studies have shown that medication-related discrepancies are common. Few
      studies report unwanted incidents by other factors than medications. In 2002 an
      ambulatory team (AT) was established within the Department of Geriatrics, St.
      Olavs University Hospital HF, Trondheim, Norway. The AT monitored the transition
      of the patients from hospital to home and four weeks after discharge in order to
      reveal unwanted incidents.The aim of the present study was to describe unwanted
      incidents registered by the AT among patients discharged from a geriatric
      evaluation and management unit (GEMU) by character, frequency and stage in the
      transitional process. Only unwanted incidents with a severity making contact with
      the primary health care (PHC) necessary were registered. METHODS: A prospective
      observational study with patients treated in the GEMU and followed by the AT was
      performed. Current practice included comprehensive geriatric assessment and
      management including discharge planning in the GEMU and collaboration with the
      primary health care on appointments on assistance to be provided after discharge
      from hospital. Unwanted incidents severe enough to induce contact with the
      primary health care were registered during the transitional phase and after
      discharge. RESULTS: 118 patients (65% female), with mean age 83.2 +/- 6.4 years
      participated. Median Barthel Index at discharge was 18 (interquartile range 16
      19) and median Mini Mental Status Examination 24 (interquartile range 21-26). A
      total of 146 unwanted incidents were registered in 70 (59%) of the patients. Most
      frequent were unwanted incidents related to drug prescription regime (32%),
      exchange of information in and between the GEMU and the primary health care (25%)
      and service or help provided from the PHC (17%). CONCLUSIONS: Despite a seemingly
      well-organised system for transition of patients from the GEMU to their homes,
      one or more unwanted incidents occurred in most patients during discharge or four
      weeks post discharge. The study has revealed areas of importance for improving
      transitional care of geriatric patients.

PMID- 20044948
TI  - Th17 responses and host defense against microorganisms: an overview.
AB  - T helper (Th) 17 cells have recently been described as a third subset of T helper
      cells, and have provided new insights into the mechanisms that are important in
      the development of autoimmune diseases and the immune responses that are
      essential for effective antimicrobial host defense. Both protective and harmful
      effects of Th17 responses during infection have been described. In general, Th17
      responses are critical for mucosal and epithelial host defense against
      extracellular bacteria and fungi. However, recent studies have reported that Th17
      responses can also contribute to viral persistence and chronic inflammation
      associated with parasitic infection. It has become evident that the type of
      microorganisms and the setting in which they trigger the Th17 response determines
      the outcome of the delicate balance that exists between Th17 induced protection
      and immunopathogenesis.

PMID- 20044946
TI  - Adaptation of Hansenula polymorpha to methanol: a transcriptome analysis.
AB  - BACKGROUND: Methylotrophic yeast species (e.g. Hansenula polymorpha, Pichia
      pastoris) can grow on methanol as sole source of carbon and energy. These
      organisms are important cell factories for the production of recombinant
      proteins, but are also used in fundamental research as model organisms to study
      peroxisome biology. During exponential growth on glucose, cells of H. polymorpha
      typically contain a single, small peroxisome that is redundant for growth while
      on methanol multiple, enlarged peroxisomes are present. These organelles are
      crucial to support growth on methanol, as they contain key enzymes of methanol
      metabolism.In this study, changes in the transcriptional profiles during
      adaptation of H. polymorpha cells from glucose- to methanol-containing media were
      investigated using DNA-microarray analyses. RESULTS: Two hours after the shift of
      cells from glucose to methanol nearly 20% (1184 genes) of the approximately 6000
      annotated H. polymorpha genes were significantly upregulated with at least a two
      fold differential expression. Highest upregulation (> 300-fold) was observed for
      the genes encoding the transcription factor Mpp1 and formate dehydrogenase, an
      enzyme of the methanol dissimilation pathway. Upregulated genes also included
      genes encoding other enzymes of methanol metabolism as well as of peroxisomal
      beta-oxidation.A moderate increase in transcriptional levels (up to 4-fold) was
      observed for several PEX genes, which are involved in peroxisome biogenesis. Only
      PEX11 and PEX32 were higher upregulated. In addition, an increase was observed in
      expression of the several ATG genes, which encode proteins involved in autophagy
      and autophagy processes. The strongest upregulation was observed for ATG8 and
      ATG11.Approximately 20% (1246 genes) of the genes were downregulated. These
      included glycolytic genes as well as genes involved in transcription and
      translation. CONCLUSION: Transcriptional profiling of H. polymorpha cells shifted
      from glucose to methanol showed the expected downregulation of glycolytic genes
      together with upregulation of the methanol utilisation pathway. This serves as a
      confirmation and validation of the array data obtained. Consistent with this,
      also various PEX genes were upregulated. The strong upregulation of ATG genes is
      possibly due to induction of autophagy processes related to remodeling of the
      cell architecture required to support growth on methanol. These processes may
      also be responsible for the enhanced peroxisomal beta-oxidation, as autophagy
      leads to recycling of membrane lipids. The prominent downregulation of
      transcription and translation may be explained by the reduced growth rate on
      methanol (td glucose 1 h vs td methanol 4.5 h).

PMID- 20044949
TI  - Functional characterization of a minimal sequence essential for the expression of
      human TLX2 gene.
AB  - TLX2 is an orphan homeodomain transcription factor whose expression is mainly
      associated with tissues derived from neural crest cells. Recently, we have
      demonstrated that PHOX2A and PHOX2B are able to enhance the neural cell-type
      specific expression of human TLX2 by binding distally the 5'-flanking region. In
      the present work, to deepen into the TLX2 transcription regulation, we have
      focused on the proximal 5'- flanking region of the gene, mapping the
      transcription start site and identifying a minimal promoter necessary and
      sufficient for the basal transcription in cell lines from different origin. Site
      directed mutagenesis has allowed to demonstrate that the integrity of this
      sequence is crucial for gene expression, while electrophoretic mobility shift
      assays and chromatin immunoprecipitation experiments have revealed that such an
      activity is dependent on the binding of a PBX factor. Consistent with these
      findings, such a basal promoter activity has resulted to be enhanced by the
      previously reported PHOX2-responding sequence.

PMID- 20044950
TI  - Agrocybe chaxingu polysaccharide prevent inflammation through the inhibition of
      COX-2 and NO production.
AB  - The inhibition of nitric oxide (NO) and cyclooxygenase-2 (COX-2) production is
      considered to be a promising approach to the treatment of various diseases,
      including inflammation and cancer. In this study, we examined the effects of the
      Agrocybe chaxingu beta-glucan (polysaccharide) on lipopolysaccaride (LPS)-induced
      nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression in murine macrophage
      Raw 264.7 cells as well as 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear
      edema in mice. The polysaccharide significantly inhibited (P 0.01) LPS-induced
      iNOS and COX-2 expression levels in the cells. Furthermore, topical application
      of polysaccharide resulted in markedly inhibited (P 0.01) TPA-induced ear edema
      in mice. These results suggest that this polysaccharide may be used for NO- and
      COX-2-related disorders such as inflammation and cancer.

PMID- 20044951
TI  - Bevacizumab accelerates corneal wound healing by inhibiting TGF-beta2 expression
      in alkali-burned mouse cornea.
AB  - This study investigated the effect of subconjunctival injections of bevacizumab,
      an anti-VEGF antibody, on processes involved in corneal wound healing after
      alkali burn injury. Mice were divided into three groups: Group 1 was the saline
      treated control, group 2 received subconjunctival injection of bevacizumab 1 hr
      after injury and group 3 received bevacizumab 1 hr and 4 days after injury.
      Cornea neovascularization and opacity were observed using a slit lamp microscope.
      Corneal repair was assessed through histological analysis and immunostaining for
      CD31, alpha-SMA, collagen I, and TGF-beta2 7 days post-injury. In group 3,
      injection of bevacizumab significantly lowered neovascularization and improved
      corneal transparency. Immunostaining analysis demonstrated a reduction in CD31,
      alpha-SMA and TGF-beta2 levels in stroma compared to group 1. These results
      indicate that bevacizumab may be useful in reducing neovascularization and
      improving corneal transparency following corneal alkali burn injury by
      accelerating regeneration of the basement membrane.

PMID- 20044952
TI  - Induction of caspase-dependent apoptosis in melanoma cells by the synthetic
      compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea.
AB  - Recently, various phenolic acid phenethyl ureas (PAPUs) have been synthesized
      from phenolic acids by Curtius rearrangement for the development of more
      effective anti-oxidants. In this study, we examined the anti-tumor activity and
      cellular mechanism of the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3
      styrylurea (PAPU1) using melanoma B16/F10 and M-3 cells. Results showed that
      PAPU1 inhibited the cell proliferation and viability, but did not induce
      cytotoxic effects on primary cultured fibroblasts. PAPU1 induced apoptotic cell
      death rather than necrosis in melanoma cells, a result clearly proven by the
      shift of cells into sub-G1 phase of the cell cycle and by the substantial
      increase in cells positively stained with TUNEL or Annexin V. Collectively, this
      study revealed that PAPU1 induced apoptosis in a caspase-dependent manner,
      suggesting a potential role as a cancer chemopreventive agent for melanoma cells.

PMID- 20044953
TI  - Aspartyl aminopeptidase of Schizosaccharomyces pombe has a molecular chaperone
      function.
AB  - To screen chaperone proteins from Schizosaccharomyce pombe (S. pombe), we
      prepared recombinant citrate synthase of the fission yeast as a substrate of anti
      aggregation assay. Purified recombinant citrate synthase showed citrate synthase
      activity and was suitable for the substrate of chaperone assay. Several heat
      stable proteins including aspartyl aminopeptidase (AAP) for candidates of
      chaperone were screened from the supernatant fraction of heat-treated crude
      extract of S. pombe. The purified AAP migrated as a single band of 47 kDa on SDS
      polyacrylamide gel electrophoresis. The native size of AAP was estimated as 200
      kDa by a HPLC gel permeation chromatography. This enzyme can remove the aspartyl
      residue at N-terminus of angiotensin I. In addition, AAP showed the heat
      stability and protected the aggregation of citrate synthase caused by thermal
      denaturation. This study showed that S. pombe AAP is a moonlight protein that has
      aspartyl aminopeptidase and chaperone activities.

PMID- 20044954
TI  - Regulation of type-1 protein phosphatase in a model of metabolic arrest.
AB  - Type-1 phosphatase (PP-1) was assessed in foot muscle (FM) and hepatopancreas
      (HP) of estivating (EST) Otala lactea. Snail PP-1 displayed several conserved
      traits, including sensitivity to inhibitors, substrate affinity, and reduction in
      size to a 39 kDa catalytic subunit (PP-1c). During EST, PP-1 activity in FM and
      HP crude extracts was reduced, though kinetics and protein levels of purified PP
      1c isoforms were not altered. PP-1c protein levels increased and decreased in
      nuclear and glycogen-associated fractions, respectively, during EST. Gel
      filtration determined that a 257 kDa low K(m) PP-1alpha complex decreased during
      estivation whereas a 76 kDa high K(m) complex increased in EST. Western blotting
      confirmed that the 76 kDa protein consisted of PP-1alpha and nuclear inhibitor of
      PP-1 (NIPP-1). A suppression of PP-1 activity factors in the overall metabolic
      rate depression in estivating snails and the mechanism is mediated through
      altered cellular localization and interaction with binding partners.

PMID- 20044955
TI  - CONVIRT: a web-based tool for transcriptional regulatory site identification
      using a conserved virtual chromosome.
AB  - Techniques for analyzing protein-DNA interactions on a genome-wide scale have
      recently established regulatory roles for distal enhancers. However, the large
      sizes of higher eukaryotic genomes have made identification of these elements
      difficult. Information regarding sequence conservation, exon annotation and
      repetitive regions can be used to reduce the size of the search region. However,
      previously developed resources are inadequate for consolidating such information.
      CONVIRT is a web resource for the identification of transcription factor binding
      sites and also features comparative genomics. Genomic information on ortholog
      independent conserved regions, exons, repeats and sequences is integrated into
      the virtual chromosome, and statistically over-represented single or combinations
      of transcription factor binding sites are sought. CONVIRT provides regulatory
      network analysis for several organisms with long promoter regions and permits
      inter-species genome alignments. CONVIRT is freely available at
      http://biosoft.kaist. ac.kr/convirt.

PMID- 20044956
TI  - Role of the surface loop on the structure and biological activity of angiogenin.
AB  - Angiogenin is a member of the ribonuclease superfamily that induces the formation
      of new blood vessels. It has been suggested that the surface loop of angiogenin
      defined by residues 59-71 plays a special role in angiogenic function (1);
      however, the mechanism of action is not clearly defined. To elucidate the role of
      the surface loop on the structure, function and stability of angiogenin, three
      surface loop mutants were produced in which 14 amino acids in the surface loop of
      RNase A were substituted for the 13 amino acids in the corresponding loop of
      angiogenin. The structure, stability and biological functions of the mutants were
      then investigated using biophysical and biological approaches. Even though the
      substitutions did not influence the overall structure of angiogenin, they
      affected the stability and angiogenic function of angiogenin, indicating that the
      surface loop of angiogenin plays a significant role in maintaining the stability
      and angiogenic function of angiogenin.

PMID- 20044957
TI  - Putative association of DNA methyltransferase 1 (DNMT1) polymorphisms with
      clearance of HBV infection.
AB  - DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation,
      which often occurs in CpG islands located near the regulatory regions of genes
      and affects transcription of specific genes. In this study, we examined the
      possible association of DNMT1 polymorphisms with HBV clearance and the risk of
      hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by
      considering their allele frequencies, haplotype-tagging status and LDs for
      genotyping in larger-scale subjects (n = 1,100). Statistical analysis
      demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T,
      showed significant association with HBV clearance in a co-dominant model (OR =
      1.30, P(corr) = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, P(corr) =
      0.01-0.03), respectively. These results suggest that two intron polymorphisms of
      DNMT1,+34542G > C and +38565G > T, might affect HBV clearance.

PMID- 20044958
TI  - Casein kinase 2 interacts with human mitogen- and stress-activated protein kinase
      MSK1 and phosphorylates it at multiple sites.
AB  - Mitogen- and stress-activated protein kinase (MSK1) palys a crucial role in the
      regulation of transcription downstream of extracellular-signal-regulated
      kinase1/2 (ERK1/2) and mitogen- activated protein kinase p38. MSK1 can be
      phosphorylated and activated in cells by both ERK1/2 and p38alpha. In this study,
      Casein Kinase 2 (CK2) was identified as a binding and regulatory partner for
      MSK1. Using the yeast two-hybrid system, MSK1 was found to interact with the
      CK2beta regulatory subunit of CK2. Interactions between MSK1 and the CK2alpha
      catalytic subunit and CK2beta subunit were demonstrated in vitro and in vivo. We
      further found that CK2alpha can only interact with the C-terminal kinase domain
      of MSK1. Using site-directed mutagenesis assay and mass spectrometry, we
      identified five sites in the MSK1 C-terminus that could be phosphorylated by CK2
      in vitro: Ser757, Ser758, Ser759, Ser760 and Thr793. Of these, Ser757, Ser759,
      Ser760 and Thr793 were previously unknown.

PMID- 20044960
TI  - Obesity in the Inuit--adipose tissue and ischaemic heart disease.

PMID- 20044961
TI  - Acylation stimulating protein is higher in Inuit from Nunavik compared to a
      southern Quebec population.
AB  - OBJECTIVES: The Inuit of Nunavik in northern Quebec have a lower risk for
      ischemic heart disease (IHD) compared to Caucasian populations. Acylation
      stimulating protein (ASP), which is involved in the storage of dietary fat, may
      play a role. The objective of the study was to determine plasma concentration of
      ASP in an Inuit and a southern Quebec Caucasian population. STUDY DESIGN: This is
      a cross-sectional study evaluating the relationship between ASP and dietary
      factors, such as retinol, whose intake is higher in the Inuit. As well,
      concentrations of ASP were evaluated in relationship to components of the
      metabolic syndrome. METHODS: Medical history was collected via a questionnaire
      and anthropometric measurements and blood samples were collected. RESULTS: ASP
      was significantly higher in both the Inuit men and women compared to Caucasian
      men (66.1 +/- 4.1 nM vs 27.5 +/- 2.5 nM, p < 0.0001) and women (71.8 +/- 3.8 nM
      vs 29.4 +/- 1.3 nM, p < 0.0001). In addition, ASP significantly correlated with
      total retinol (r = 0.17, p = 0.02) and free retinol (r = 0.15, p = 0.04) in Inuit
      men but not with other distinctive dietary markers such as omega-3 fatty acids.
      CONCLUSIONS: Inuit men and women have higher ASP which was unrelated to the
      number of risk factors for IHD that were present.

PMID- 20044962
TI  - Increasing rates of diabetes and cardiovascular risk in Metis Settlements in
      northern Alberta.
AB  - OBJECTIVES: To determine the prevalence of diabetes (using secondary data
      analysis), as well as undiagnosed diabetes and pre-diabetes (using primary
      research methods) among adult Metis Settlement dwellers in northern Alberta. We
      also sought to identify cardiovascular risk factors. STUDY DESIGN: Quantitative
      research study utilizing both population census and community-based diabetes
      screening data. METHODS: Self-reported diabetes was analyzed from the results of
      the Metis Settlement specific censuses in 1998 and 2006. Mobile clinics travelled
      into each of the 8 Metis Settlement communities in Alberta recruiting 693
      subjects for screening for undiagnosed diabetes, pre-diabetes and metabolic
      syndrome. Logistic regression analyses (adjusted for age and sex) were used to
      identify associated factors. RESULTS: According to the censuses, 4,312 Metis
      individuals were living on Settlements in 1998 and 5,059 in 2006. Self-reported
      age-adjusted prevalence of diabetes increased significantly from 5.1% in 1998 to
      6.9% in 2006 (p < 0.01), with a crude prevalence increase of 66% (p < 0.01). In
      2006, diabetes prevalence was higher among females than males, 7.8% vs. 6.1%
      respectively (p < 0.05). Of the 266 adults screened in the fasting state, 5.3%
      had undiagnosed diabetes, whereas 20.3% (Canadian Diabetes Association criteria)
      and 51.9% (American Diabetes Association criteria) had pre-diabetes. Rates of
      obesity and metabolic syndrome were 49.4% (n = 693) and 46.4% (n = 266),
      respectively. Hemoglobin A1c > 6.1% was strongly associated with diabetes, pre
      diabetes and metabolic syndrome. CONCLUSIONS: Our results indicate high rates of
      diabetes, undiagnosed diabetes, pre-diabetes and metabolic syndrome among adult
      Alberta Metis Settlement dwellers.

PMID- 20044963
TI  - The current state of birth outcome and birth defect surveillance in northern
      regions of the world.
AB  - OBJECTIVES: Little is known about the rates of congenital anomalies in the
      northernmost regions of the world. As in other parts of the world, it is crucial
      to assess the relative rates and trends of adverse birth outcomes and birth
      defects, as indicators of population health and to develop public health
      strategies for prevention. The aim of this review is to catalogue existing and
      developing birth outcome and birth defect surveillance within and around the
      geographic jurisdiction of the International Union of Circumpolar Health (IUCH).
      STUDY DESIGN: Descriptive study. METHODS: The representatives of the IUCH Birth
      Defects Working Group catalogued existing and developing birth and birth defect
      surveillance systems and the extent of information they contain to determine
      inter-regional comparability. RESULTS: Systematic population-based registration
      of birth outcomes including birth defects occurs to some degree in all
      circumpolar countries, but the quality of collection and the coverage in
      northernmost regions vary. There are limited circumpolar jurisdictions with
      surveillance systems collecting birth defect information beyond the perinatal
      period. Efforts are underway in Canada and Russia to improve the quality and
      comprehensiveness of the information collected in the northern regions.
      CONCLUSIONS: Although there is variability in the comprehensiveness of
      information collected in northern jurisdictions limiting sophisticated
      comparative analyses between regions, there is untapped potential for baseline
      analyses of specific risks and outcomes that could provide insight into
      geographic differences and gaps in surveillance that could be improved.

PMID- 20044964
TI  - Early childhood hemoglobin level is a strong predictor of hemoglobin levels
      during later childhood among low-income Alaska children.
AB  - OBJECTIVES: For unknown reasons, Arctic Indigenous children have iron deficiency
      and anemia prevalences up to 10 times higher than national reference populations.
      The current study sought to identify the importance of Alaska Native status,
      residence and hemoglobin (Hb) level at age 10 to 23 months for predicting Hb
      levels at age 24 to 59 months when controlling for potential confounders. STUDY
      DESIGN: Retrospective cohort. METHODS: A birth certificate database was linked to
      a database containing hemoglobin levels determined through the U.S. Supplemental
      Nutrition Program for Women, Infants and Children (WIC) among Alaskan children
      age 10 to 59 months evaluated from 1999-2006. RESULTS: Of children with a birth
      certificate matched to WIC data, Alaska Native status and residence in western
      and northern Alaska were associated strongly with anemia at both ages.
      Nevertheless, of 5,796 children with Hb levels determined at both ages, the
      single strongest predictor of Hb level at age 24 to 59 months was Hb level at age
      10 to 23 months. The community-level anemia prevalence among children age 10 to
      23 months was predictive of community-level anemia prevalence among children age
      24 to 59 months. CONCLUSIONS: The early onset of anemia and the strong
      association between earlier and later Hb levels or anemia at both the individual
      and community levels suggest a role for prenatal effects that remain until at
      least age 5 years. This is true particularly of Yupik and Inupiat children, who
      make up the primary residents of western and northern Alaska.

PMID- 20044965
TI  - The social determinants of Inuit health: a focus on social support in the
      Canadian Arctic.
AB  - OBJECTIVES: Societies that foster socially supportive networks produce healthier
      populations. Social support is a significant determinant of health among Canada's
      Inuit population; however, little is known about the characteristics that provide
      access to social support among Inuit. This exploratory analysis describes how 4
      types of social support (namely, positive social interaction, emotional support,
      tangible support and affection and intimacy) differ in relation to various
      determinants of health. STUDY DESIGN: Micro-data from the Arctic Supplement of
      the 2001 Aboriginal Peoples Survey (n = 26,290) was used. METHODS: Cross
      tabulations and multivariate logistic regression analyses were used to examine
      levels (high/low) of the 4 types of social support among the full Inuit sample (n
      = 26,290) as they relate to age, gender, geographic region, marital status,
      Aboriginal language use and participation in traditional harvesting activities.
      RESULTS: Certain subsegments of the Inuit population were less likely to report
      high levels of social support, including men, the elderly (aged 55+) and the
      unmarried. Some Inuit-relevant determinants were also found to decrease the odds
      of reporting high levels of social support, including being unable to speak or
      understand an Aboriginal language, not participating in traditional harvesting
      activities and living in Nunavik. CONCLUSIONS: Research that frames Inuit health
      within the social determinants of health is in its relative infancy; however,
      evidence from the social epidemiological literature indicates that those with
      diminished access to social support also suffer poorer health outcomes. Future
      research should build on the findings of this study to examine how the
      relationship between various health outcomes (e.g., respiratory disease, suicide
      attempts, self-rated health) and social support may respond along a social
      gradient. Such analysis will build on the paucity of literature specific to Inuit
      health and social conditions and set priorities for policy and programming
      efforts that will improve the social determinants of Inuit health.

PMID- 20044966
TI  - Should traditional healing be integrated within the mental health services in
      Sami areas of northern Norway? Patient views and related factors.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether including
      traditional healing methods within mental health services is desirable among
      users of these services in Sami areas of northern Norway. STUDY DESIGN: A cross
      sectional questionnaire based survey among users of the mental health services in
      Finnmark and Nord-Troms Norway. METHODS: The percentages of participants desiring
      traditional healing modalities within the health services were calculated, and
      univariate and multivariate analysis were performed with respect to factors
      associated with a desire for integration. RESULTS: A total of 186 users responded
      to the survey, of which 72 reported some degree of Sami cultural affiliation.
      Forty-eight had Sami-speaking grandparents on both sides of the family. The
      desire for the integration of traditional healing was high among all with a Sami
      cultural background. Eighty-one percent of those with Sami speaking grandparents
      on both sides of the family desired such an integration. In a regression
      analysis, both Sami affiliation and having used traditional healing forms were
      significantly associated with a desire for the integration of traditional healing
      within mental health services. CONCLUSIONS: The integration of traditional
      healing methods within health services has been suggested both by the World
      Health Organization and is used in some of the services to Indigenous populations
      in Western countries. This study shows that such integration is desirable among
      Sami users of mental health services in Norway.

PMID- 20044967
TI  - Young students as participants in school health promotion: an intervention study
      in a Swedish elementary school.
AB  - OBJECTIVES: The aim was to analyse if young students could be substantive
      participants in a health-promoting school project. The specific aims were to
      analyse the changes the students proposed in their school environment, how these
      changes were prioritized by a school health committee and to discuss the
      students' proposals and the changes from a health and gender perspective. STUDY
      DESIGN: An intervention project was carried out in an elementary school with
      students (about 150) in Grades 1 through 6. The intervention included small-group
      discussions about health promoting factors, following a health education model
      referred to as "It's your decision." At the last of 6 discussions, the students
      made suggestions for health-promoting changes in their school environment. A
      health committee was established with students and staff for the purpose of
      initiating changes based on the proposals. METHODS: A content analysis was used
      to analyse the proposals and the protocols developed by the health committee.
      RESULTS: The analysis showed 6 categories of the students' proposals: social
      climate, influence on schoolwork, structure and orderliness, security, physical
      environment and food for well-being. Their priorities corresponded to the
      students' categories, but had an additional category regarding health education.
      CONCLUSIONS: Principles that guide promoting good health in schools can be put
      into action among students as young as those in Grades 1 through 6. Future
      challenges include how to convey experiences and knowledge to other schools and
      how to evaluate if inequalities in health because of gender, class and ethnicity
      can be reduced through the focus on empowerment and participation.

PMID- 20044968
TI  - The Circumpolar Inuit Health Summit: a summary.

PMID- 20044969
TI  - Immunohistochemical study of Langerhans cells in cutaneous lesions of the Jorge
      Lobo's disease.
AB  - Jorge Lobo's disease is a chronic infection caused by the fungus Lacazia loboi
      endemic in South America. The infection is characterized by the appearance of
      parakeloidal, ulcerated or verrucous nodular or plaque-like cutaneous lesions.
      The histopathological aspect is characterized by poorly organized granulomas with
      histiocytes and multinucleated giant cells. Little is known about local immune
      response in lobomycosis skin lesions. Thirty-three skin biopsies from patients
      with Jorge Lobo's disease were selected from Ambulatory of Dermatology, UFPA. The
      control group was constituted by ten biopsies from normal skin. Langerhans cells
      were identified by immunohistochemistry using anti-CD1a antibody (Serotec). The
      number of positive cells was statistically analyzed. Langerhans cells were
      visualized along the epidermis in biopsies from Jorge Lobo's disease and the
      morphology and the number of Langerhans cells did not differ from normal skin
      (p>0.05). In Jorge Lobo's disease, this cell population probably presents some
      escape mechanism of the local immune system to evade the antigen presentation by
      those cells.

PMID- 20044970
TI  - Transfusion transmitted Chagas disease: is it really under control?
AB  - Transfusion transmitted Chagas disease was recognized as a medical problem more
      than 50 years ago. However, little attention was paid to it by Transfusion
      Medicine, medical authorities or regulatory agencies as a major problem and
      threat (especially after the advent of HIV/AIDS); perhaps because it was mainly
      restricted to tropical regions, usually in less developed countries. With the
      intense human migratory movement from developing to developed countries, it
      became more common and evident. The scope of this review is to cover the main
      transfusional aspects of American trypanosomiasis (Chagas disease), including the
      main strategies to prevent it through donor questionnaires, specific serological
      testing and alternative methods such as leukofiltration and pathogen reduction
      procedures, in order to increase the blood safety in both developing and
      developed countries.

PMID- 20044971
TI  - Stimulation of F(1)-ATPase activity by sodium dodecyl sulfate.
AB  - F(1)-ATPase is a rotary molecular motor in which the gamma subunit rotates inside
      the cylinder made of alpha(3)beta(3) subunits. We have studied the effects of
      sodium dodecyl sulfate (SDS) on the rotational and ATP hydrolysis activities of
      F(1)-ATPase. Bulk hydrolysis activity at various SDS concentrations was examined
      at 2mM ATP. Maximal stimulation was obtained at 0.003% (w/v) SDS, the initial
      (least inhibited) activity being about 1.4 times and the steady-state activity 3
      4 times the values in the absence of SDS. Rotation rates observed with a 40-nm
      gold bead or a 0.29-mum bead duplex as well as the torque were unaffected by the
      presence of 0.003% SDS. The fraction of beads that rotated, in contrast, tended
      to increase in the presence of SDS. SDS seems to bring inactive F(1) molecules
      into an active form but it does not alter or enhance the function of already
      active F(1) molecules significantly.

PMID- 20044972
TI  - Mitochondrial ion transport pathways: role in metabolic diseases.
AB  - Mitochondria are the central coordinators of energy metabolism and alterations in
      their function and number have long been associated with metabolic disorders such
      as obesity, diabetes and hyperlipidemias. Since oxidative phosphorylation
      requires an electrochemical gradient across the inner mitochondrial membrane, ion
      channels in this membrane certainly must play an important role in the regulation
      of energy metabolism. However, in many experimental settings, the relationship
      between the activity of mitochondrial ion transport and metabolic disorders is
      still poorly understood. This review briefly summarizes some aspects of
      mitochondrial H+ transport (promoted by uncoupling proteins, UCPs), Ca2+ and K+
      uniporters which may be determinant in metabolic disorders.

PMID- 20044973
TI  - Structural and functional changes in a synthetic S5 segment of KvLQT1 channel as
      a result of a conserved amino acid substitution that occurs in LQT1 syndrome of
      human.
AB  - Mutations in various voltage gated cardiac ion channels are the cause of
      different forms of long QT syndrome (LQTS), which is an inherited arrhythmic
      disorder marked as a prolonged QT interval on electrocardiogram. Of these LQTS1
      is associated with mutations in the gene encoding KCNQ1 (KvLQT1) channel. One
      responsible mutation, G269S, in the S5 segment of KvLQT1, that affects the proper
      expression and function of channel protein leads to LQTS1. Our objective was to
      study how G269S mutation interferes with the structure and function of a
      synthetic S5 segment of KvLQT1 channel. One wild type 22-residue peptide and
      another mutant peptide of the same length with G269S mutation, derived from the
      S5 segment were synthesized and labeled with fluorescent probes. The mutant
      peptide exhibited lower affinity towards phospholipid vesicles as compared to the
      wild type peptide and showed impaired assembly and localization onto the lipid
      vesicles as evidenced by membrane-binding, energy transfer and proteolytic
      cleavage experiments. Loss in the helical content of S5 mutant peptide in
      membrane-mimetic environments was observed. Furthermore, it was observed that
      G269S mutation significantly inhibited the ability of S5 peptide to permeabilize
      the lipid vesicles. The present studies show the basis of change in function of
      the selected S5 segment as a result of G269S mutation which is associated with
      LQT1 syndrome. We speculate that the structural and functional changes related to
      the glycine to serine amino acid substitution in the S5 segment may also
      influence the activity of the whole KvLQT1 channel.

PMID- 20044974
TI  - Nanomechanics of lipid bilayers by force spectroscopy with AFM: a perspective.
AB  - Lipid bilayers determine the architecture of cell membranes and regulate a myriad
      of distinct processes that are highly dependent on the lateral organization of
      the phospholipid molecules that compose the membrane. Indeed, the mechanochemical
      properties of the membrane are strongly correlated with the function of several
      membrane proteins, which demand a very specific, highly localized physicochemical
      environment to perform their function. Several mesoscopic techniques have been
      used in the past to investigate the mechanical properties of lipid membranes.
      However, they were restricted to the study of the ensemble properties of giant
      bilayers. Force spectroscopy with AFM has emerged as a powerful technique able to
      provide valuable insights into the nanomechanical properties of supported lipid
      membranes at the nanometer/nanonewton scale in a wide variety of systems. In
      particular, these measurements have allowed direct measurement of the molecular
      interactions arising between neighboring phospholipid molecules and between the
      lipid molecules and the surrounding solvent environment. The goal of this review
      is to illustrate how these novel experiments have provided a new vista on
      membrane mechanics in a confined area within the nanometer realm, where most of
      the specific molecular interactions take place. Here we report in detail the main
      discoveries achieved by force spectroscopy with AFM on supported lipid bilayers,
      and we also discuss on the exciting future perspectives offered by this growing
      research field.

PMID- 20044976
TI  - Lipid domain separation, bilayer thickening and pearling induced by the cell
      penetrating peptide penetratin.
AB  - Protein membrane transduction domains are able to translocate through cell
      membranes. This capacity resulted in new concepts on cell communication and in
      the design of vectors for internalization of active molecules into cells.
      Penetratin crosses the plasma membrane by a receptor and metabolic energy
      independent mechanism which is at present unknown. A better knowledge of its
      interaction with phospholipids will help to understand the molecular mechanisms
      of cell penetration. Here, we investigated the role of lipid composition on
      penetratin induced membrane perturbations by X-ray diffraction, microscopy and
      (31)P-NMR. Penetratin showed the ability to induce phospholipid domain
      separation, membrane bilayer thickening, formation of vesicles, membrane
      undulations and tubular pearling. These data demonstrate its capacity to increase
      membrane curvature and suggest that dynamic phospholipid-penetratin complexes can
      be organized in different structural arrangements. These properties and their
      implications in peptide membrane translocation capacity are discussed.

PMID- 20044975
TI  - (15)N Solid-state NMR spectroscopic studies on phospholamban at its
      phosphorylated form at ser-16 in aligned phospholipid bilayers.
AB  - Wild-type phospholamban (WT-PLB) is a pentameric transmembrane protein that
      regulates the cardiac cycle (contraction and relaxation). From a physiological
      prospective, unphosphorylated WT-PLB inhibits sarcoplasmic reticulum ATPase
      activity; whereas, its phosphorylated form relieves the inhibition in a mechanism
      that is not completely understood. In this study, site-specifically (15)N-Ala-11-
      and (15)N-Leu-7-labeled WT-PLB and the corresponding phosphorylated forms (P-PLB)
      were incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine/2-dioleoyl-sn
      glycero-3-phosphoethanolamine (DOPC/DOPE) mechanically oriented lipid bilayers.
      The aligned (15)N-labeled Ala-11 and Leu-7 WT-PLB samples show (15)N resonance
      peaks at approximately 71ppm and 75ppm, respectively, while the corresponding
      phosphorylated forms P-PLB show (15)N peaks at 92ppm and 99ppm, respectively.
      These (15)N chemical shift changes upon phosphorylation are significant and in
      agreement with previous reports, which indicate that phosphorylation of WT-PLB at
      Ser-16 alters the structural properties of the cytoplasmic domain with respect to
      the lipid bilayers.

PMID- 20044977
TI  - Sterol affinity for bilayer membranes is affected by their ceramide content and
      the ceramide chain length.
AB  - It is known that ceramides can influence the lateral organization in biological
      membranes. In particular ceramides have been shown to alter the composition of
      cholesterol and sphingolipid enriched nanoscopic domains, by displacing
      cholesterol, and forming gel phase domains with sphingomyelin. Here we have
      investigated how the bilayer content of ceramides and their chain length
      influence sterol partitioning into the membranes. The effect of ceramides with
      saturated chains ranging from 4 to 24 carbons in length was investigated. In
      addition, unsaturated 18:1- and 24:1-ceramides were also examined. The sterol
      partitioning into bilayer membranes was studied by measuring the distribution of
      cholestatrienol, a fluorescent cholesterol analogue, between methyl-beta
      cyclodextrin and large unilamellar vesicle with defined lipid composition. Up to
      15 mol% ceramide was added to bilayers composed of DOPC:PSM:cholesterol (3:1:1),
      and the effect on sterol partitioning was measured. Both at 23 and 37 degrees C
      addition of ceramide affected the sterol partitioning in a chain length dependent
      manner, so that the ceramides with intermediate chain lengths were the most
      effective in reducing sterol partitioning into the membranes. At 23 degrees C the
      18:1-ceramide was not as effective at inhibiting sterol partitioning into the
      vesicles as its saturated equivalent, but at 37 degrees C the additional double
      bond had no effect. The longer 24:1-ceramide behaved as 24:0-ceramide at both
      temperatures. In conclusion, this work shows how the distribution of sterols
      within sphingomyelin-containing membranes is affected by the acyl chain
      composition in ceramides. The overall membrane partitioning measured in this
      study reflects the differential partitioning of sterol into ordered domains where
      ceramides compete with the sterol for association with sphingomyelin.

PMID- 20044978
TI  - Vesicles with charged domains.
AB  - This work summarizes results obtained on membranes composed of the ternary
      mixture dioleoylphosphatidylglycerol (DOPG), egg sphingomyelin (eSM) and
      cholesterol (Chol). The membrane phase state as a function of composition is
      characterized from data collected with fluorescence microscopy on giant
      unilamellar vesicles. The results suggest that the presence of the charged DOPG
      significantly decreases the composition region of coexistence of liquid ordered
      and liquid disordered phases as compared to that in the ternary mixture of
      dioleoylphosphatidycholine, sphingomyelin and cholesterol. The addition of
      calcium chloride to DOPG:eSM:Chol vesicles, and to a lesser extent the addition
      of sodium chloride, leads to the stabilization of the two-phase coexistence
      region, which is expressed in an increase in the miscibility temperature. On the
      other hand, addition of the chelating agent EDTA has the opposite effect,
      suggesting that impurities of divalent cations in preparations of giant vesicles
      contribute to the stabilization of charged domains. We also explore the behavior
      of these membranes in the presence of extruded unilamellar vesicles made of the
      positively charged lipid dioleoyltrimethylammoniumpropane (DOTAP). The latter can
      induce domain formation in DOPG:eSM:Chol vesicles with initial composition in the
      one-phase region.

PMID- 20044979
TI  - Identification of chemerin receptor (ChemR23) in human endothelial cells:
      chemerin-induced endothelial angiogenesis.
AB  - Chemerin acting via its distinct G protein-coupled receptor CMKLR1 (ChemR23), is
      a novel adipokine, circulating levels of which are raised in inflammatory states.
      Chemerin shows strong correlation with various facets of the metabolic syndrome;
      these states are associated with an increased incidence of cardiovascular disease
      (CVD) and dysregulated angiogenesis. We therefore, investigated the regulation of
      ChemR23 by pro-inflammatory cytokines and assessed the angiogenic potential of
      chemerin in human endothelial cells (EC). We have demonstrated the novel presence
      of ChemR23 in human ECs and its significant up-regulation (P<0.001) by pro
      inflammatory cytokines, TNF-alpha, IL-1beta and IL-6. More importantly, chemerin
      was potently angiogenic, as assessed by conducting functional in-vitro angiogenic
      assays; chemerin also dose-dependently induced gelatinolytic (MMP-2 & MMP-9)
      activity of ECs (P<0.001). Furthermore, chemerin dose-dependently activated
      PI3K/Akt and MAPKs pathways (P<0.01), key angiogenic and cell survival cascades.
      Our data provide the first evidence of chemerin-induced endothelial angiogenesis
      and MMP production and activity.

PMID- 20044980
TI  - Heart rhythm genomic fabric in hypoxia.
AB  - The molecular mechanisms by which chronic hypoxia, whether constant (CCH) or
      intermittent (CIH), alters the heart rhythm are still under debate. Expression
      level, control, maturational profile and intercoordination of 54 genes encoding
      heart rhythm determinants (HRDs) were analyzed in 36 mice subjected for 1, 2 or 4
      weeks of their early life to normal atmospheric conditions or to CCH or CIH. Our
      analysis revealed a complex network of genes encoding various heart rate,
      inotropy and development controllers, receptors, ion channels and transporters,
      ankyrins, epigenetic modulators and intercalated disc components (adherens,
      cadherins, catenins, desmosomal, gap and tight junction proteins). The network is
      remodeled during maturation and substantially and differently altered by CIH and
      CCH. Gene Prominence Analysis that ranks the genes according to their expression
      stability and networking within functional gene webs, confirmed the HRD status of
      certain epigenetic modulators and components of the intercalated discs not yet
      associated with arrhythmia.

PMID- 20044981
TI  - Is the periaqueductal gray an essential relay center for the micturition reflex
      pathway in the cat?
AB  - The periaqueductal gray (PAG), especially in a region between the levels the
      oculomotor nucleus and the trochlear nucleus, was suggested to be the essential
      relay center that conveys information of bladder fullness to the pontine
      micturition center (Barrington's nucleus). The present study examined this
      hypothesis by transecting the brainstem in anesthetized cats. In eight cases of
      the midbrain transection, all (n=3) or most (n=5) of the PAG between the levels
      the oculomotor nucleus and the trochlear nucleus was separated from the intact
      side of the brain. Furthermore, in the former three cases, the PAG at the level
      caudal to the trochlear nucleus was separated from the intact brain by more than
      half (n=2) or completely (n=1). In all these cases, there were no remarkable
      differences in the amplitude of the micturition contraction (80-98% of that
      before transection), irrespective of the levels of the transection. In the cases
      of the pontine transection, micturition contraction disappeared after transecting
      through the caudal part of Barrington's nucleus (n=1) or through regions caudal
      to this nucleus (n=5). In the one case that received a transection through the
      rostral part of Barrington's nucleus, the amplitude of the micturition
      contraction was 43% of that before transection. This study demonstrates that
      Barrington's nucleus is essential, but the PAG is not essential, for evoking
      micturition. Our results suggest that the information of bladder fullness in the
      cat is conveyed to Barrington's nucleus either directly from the lumbosacral
      neurons or indirectly via relay neurons located below the midbrain.

PMID- 20044982
TI  - Why the white bear is still there: electrophysiological evidence for ironic
      semantic activation during thought suppression.
AB  - Much research has focused on the paradoxical effects of thought suppression,
      leading to the viewpoint that increases in unwanted thoughts are due to an ironic
      monitoring process that increases the activation of the very thoughts one is
      trying to rid from consciousness. However, it remains unclear from behavioral
      findings whether suppressed thoughts become more accessible during the act of
      suppression. In the current study, event-related potentials were recorded while
      participants suppressed or expressed thoughts of a focus word during a simple
      lexical decision task. Modulations in the N400 component reported here
      demonstrate the paradoxical effects occurring at the semantic level during
      suppression, as well as some evidence for the rebound effect after suppression
      periods. Interestingly, semantic activation was greater for focus words during
      suppression than expression, despite differences in the N1 window suggesting that
      expression elicited greater perceptual processing than suppression. Results
      provide electrophysiological evidence for the Ironic Process model and support
      recent claims of asymmetric network activation during thought suppression.

PMID- 20044983
TI  - Tamoxifen alleviates irradiation-induced brain injury by attenuating microglial
      inflammatory response in vitro and in vivo.
AB  - Irradiation-induced brain injury, leading to cognitive impairment several months
      to years after whole brain irradiation (WBI) therapy, is a common health problem
      in patients with primary or metastatic brain tumor and greatly impairs quality of
      life for tumor survivors. Recently, it has been demonstrated that a rapid and
      sustained increase in activated microglia following WBI led to a chronic
      inflammatory response and a corresponding decrease in hippocampal neurogenesis.
      Tamoxifen, serving as a radiosensitizer and a useful agent in combination therapy
      of glioma, has been found to exert anti-inflammatory response both in cultured
      microglial cells and in a spinal cord injury model. In the present study, we
      investigated whether tamoxifen alleviated inflammatory damage seen in the
      irradiated microglia in vitro and in the irradiated brain. Irradiating BV-2 cells
      (a murine microglial cell line) with various radiation doses (2-10 Gy) led to the
      increase in IL-1 beta and TNF-alpha expression determined by ELISA, and the
      conditioned culture medium of irradiated microglia with 10 Gy radiation dose
      initiated astroglial activation and decreased the number of neuronal cells in
      vitro. Incubation BV-2 cells with tamoxifen (1 microM) for 45 min significantly
      inhibited the radiation-induced microglial inflammatory response. In the
      irradiated brain, WBI induced the breakdown of the blood-brain barrier
      permeability at day 1 post irradiation and tissue edema formation at day 3 post
      radiation. Furthermore, WBI led to microglial activation and reactive
      astrogliosis in the cerebral cortex and neuronal apoptosis in the CA1 hippocampus
      at day 3 post-radiation. Tamoxifen administration (i.p., 5 mg/kg) immediately
      post radiation reduced the irradiation-induced brain damage after WBI. Taken
      together, these data support that tamoxifen can decrease the irradiation-induced
      brain damage via attenuating the microglial inflammatory response.

PMID- 20044984
TI  - Influence of maternal MTHFR A1298C polymorphism on the risk in offspring of
      schizophrenia.
AB  - Several lines of evidence have suggested that two functional
      methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, C677T and A1298C,
      may be implicated in the etiology of schizophrenia. We examined these MTHFR
      polymorphisms in 111 families, composed of a patient and their parents, as well
      as 143 mothers of patients with schizophrenia and 235 age-matched mothers who had
      healthy children. The maternal MTHFR 1298C allele was associated with a
      significantly increased risk of schizophrenia (OR=1.63, 95%CI: 1.11-2.39,
      P=0.01). The haplotype analysis showed a weak association for the 1298C-677C
      haplotype (OR=1.54, 95%CI=1.03-2.29, P=0.04). Analysis of Transmission
      Disequilibrium Test (TDT) showed no preferential transmission of 1298C and 677T
      alleles from parents to probands (P=0.64 and P=0.71, respectively). Our results
      suggest that deficient MTHFR enzyme activity in pregnant women, related to the
      A1298C variant, is associated with a higher risk of having offspring affected
      with schizophrenia. Given the low sample size in this study, the present results
      seem tentative and need further studies to replicate.

PMID- 20044985
TI  - Methylation and expression analysis of tumor suppressor genes p15 and p16 in
      benzene poisoning.

PMID- 20044987
TI  - Daidzein relaxes rat cerebral basilar artery via activation of large-conductance
      Ca2+-activated K+ channels in vascular smooth muscle cells.
AB  - Daidzein, a phytoestrogen, has been reported to produce vasodilation via
      inhibition of Ca(2+) inflow. However, the involvement of large-conductance Ca(2+)
      activated K(+) (BK(Ca)) channels in the effect of daidzein is debated. Therefore,
      the present study was designed to investigate the effect of daidzein on the rat
      cerebral basilar artery and the underlying molecular mechanisms. Isolated
      cerebral basilar artery rings and single vascular smooth muscle cells (VSMCs)
      were used for vascular reactivity and electrophysiology measurements, to
      investigate the effect of daidzein on BK(Ca) channels in cerebral basilar artery
      smooth muscle. In addition, the human BK(Ca) channel alpha-subunit gene (hslo)
      was transfected into HEK293 cells, to directly assess whether daidzein activates
      BK(Ca) channels. The results showed that daidzein produced a concentration
      dependent but endothelium-independent relaxation in rat cerebral basilar
      arteries. Paxilline, a selective BK(Ca) channel blocker, significantly inhibited
      the daidzein-induced vasodilation, whereas NS1619, a selective BK(Ca) channel
      opener, enhanced the vasodilation. In the whole-cell configuration, daidzein
      increased noisy oscillation currents in cerebral basilar artery VSMCs in a
      concentration-dependent manner, and washout of daidzein or blockade of BK(Ca)
      channels with paxilline fully reversed the increase. However, daidzein did not
      substantially affect hSlo currents in HEK293 cells when applied to the outside of
      the cell membrane. In conclusion, these results indicate that the activation of
      BK(Ca) channels in VSMCs at least partly contributes to the daidzein-induced
      vasodilation of the rat cerebral basilar artery. The beta1-subunit of BK(Ca)
      channels plays a critical role in the activation of BK(Ca) currents by daidzein.

PMID- 20044988
TI  - Block of sensory neuronal Na+ channels by the secreolytic ambroxol is associated
      with an interaction with local anesthetic binding sites.
AB  - Voltage-gated Na(+) channels (Na(v)) regulate the excitability of sensory neurons
      and are potential targets for novel analgesics. The secreolytic ambroxol reduces
      pain-related behavior in rodents and alleviates pain in humans. With properties
      resembling those of local anesthetics, ambroxol has been reported to block Na(+)
      currents in sensory neurons with a preference for tetrodotoxin-resistant (TTXr)
      Na(+) currents encoded by Na(v)1.8. However, the molecular determinants for
      ambroxol-induced block of Na(+) channels and a preferential block of Na(v)1.8
      opposed to tetrodotoxin-sensitive (TTXs) Na(v) alpha-subunits have not been
      studied in detail. By means of whole-cell voltage clamp recordings, we studied
      the effects of ambroxol and local anesthetics on the recombinant TTXr subunit
      Na(v)1.8, on TTXs Na(v) alpha-subunits and on mutants of Na(v)1.4 that are
      insensitive to local anesthetics. Tonic and use-dependent block by ambroxol was
      strongly alleviated in local anesthetic-insensitive Na(v)1.4 mutants. Use
      dependent block, but not tonic block was significantly stronger on Na(v)1.8 than
      on TTXs channels. The TTXs subunit Na(v)1.3 displayed the least degree of use
      dependent block by ambroxol. The local anesthetics mepivacaine and S(-)
      bupivacaine also blocked Na(v)1.8 and TTXs channels differentially. While
      mepivacaine displayed a preferential use-dependent block of Na(v)1.8, S(-)
      bupivacaine displayed a preference for TTXs Na(+) channels. Our data show that
      ambroxol acts as a typical local anesthetic on Na(+) channels interacting with
      specific residues in the S6 segments. This property probably meditates the
      analgesic effect of ambroxol. Ambroxol preferentially blocks Na(v)1.8, however
      shares this property with established local anesthetics like mepivacaine.

PMID- 20044986
TI  - Gp93, the Drosophila GRP94 ortholog, is required for gut epithelial homeostasis
      and nutrient assimilation-coupled growth control.
AB  - GRP94, the endoplasmic reticulum Hsp90, is a metazoan-restricted chaperone
      essential for early development in mammals, yet dispensable for mammalian cell
      viability. This dichotomy suggests that GRP94 is required for the functional
      expression of secretory and/or membrane proteins that enable the integration of
      cells into tissues. To explore this hypothesis, we have identified the Drosophila
      ortholog of GRP94, Gp93, and report that Gp93 is an essential gene in Drosophila.
      Loss of zygotic Gp93 expression is late larval-lethal and causes prominent
      defects in the larval midgut, the sole endoderm-derived larval tissue. Gp93
      mutant larvae display pronounced defects in the midgut epithelium, with aberrant
      copper cell structure, markedly reduced gut acidification, atypical septate
      junction structure, depressed gut motility, and deficits in intestinal nutrient
      uptake. The metabolic consequences of the loss of Gp93-expression are profound;
      Gp93 mutant larvae exhibit a starvation-like metabolic phenotype, including
      suppression of insulin signaling and extensive mobilization of amino acids and
      triglycerides. The defects in copper cell structure/function accompanying loss of
      Gp93 expression resemble those reported for mutations in labial, an endodermal
      homeotic gene required for copper cell specification, and alpha-spectrin, thus
      suggesting an essential role for Gp93 in the functional expression of
      secretory/integral membrane protein-encoding lab protein target genes and/or
      integral membrane protein(s) that interact with the spectrin cytoskeleton to
      confer epithelial membrane specialization.

PMID- 20044989
TI  - GM1 ganglioside enhances the rewarding properties of cocaine in rats.
AB  - GM1 pretreatment enhanced the rewarding properties of cocaine as assessed in the
      conditioned place preference paradigm. This effect was shown by the lower dosage
      of cocaine necessary to induce conditioning compared with rats receiving cocaine
      alone, as well as by the fewer number of sessions necessary to induce place
      preference. GM1 pretreatment did not modify the plasma level of cocaine, but it
      induced a significant increase in the brain cocaine level compared with animals
      receiving cocaine alone. In order to evaluate the possibility that GM1
      pretreatment may alter the pharmacokinetic parameters of cocaine, the brain and
      plasma esterase activities, the plasma bound/free cocaine ratio and the brain
      blood barrier permeability to i.v. Evans Blue administration were assessed. None
      of these parameters was modified by the GM1 administration. In addition, GM1
      (100microM) did not alter the dopamine transporter inhibition induced by cocaine
      (10(-7)-10(-5)M), as determined by the uptake of [(3-)H]-dopamine in the
      microsacs of nucleus accumbens. In conclusion, GM1 pretreatment, which did not
      have any effect per se, increased the rewarding effect of cocaine, a phenomenon
      correlated with a significant increase in the brain cocaine levels. The different
      pharmacokinetic parameters evaluated, as well as the inhibitory effect of cocaine
      on the dopamine transporter, were not modified by GM1, but it modifies the brain
      cocaine disposition. Thus, the mechanisms by which GM1 enhanced the rewarding
      effects of cocaine merit further study.

PMID- 20044990
TI  - In vitro antioxidant activity of pravastatin provides vascular protection.
AB  - The production of reactive oxygen species plays roles during the development of
      endothelial dysfunction and it represents a significant prognostic factor for
      evaluating the risk of cardiovascular disease. Although statins target
      cholesterol biosynthesis, the beneficial effects on cardiovascular disease remain
      to be fully elucidated. In this work, we explored the in vitro effects of
      pravastatin on vascular functionality. We studied the effect of the incubation
      with this statin on acetylcholine relaxation using aorta from spontaneously
      hypertensive rats (SHR). Consistent with a cholesterol-independent mechanism of
      action, we show that pravastatin induces a significant improvement of endothelium
      dependent relaxation that is not completely reversed by mevalonic acid. Assays
      with 250microM of lucigenin were carried out to verify whether such action could
      be mediated by the scavenger properties of pravastatin. Treatment of aortic rings
      derived from Wistar rats with lucigenin promotes superoxide generation (O(2)(-))
      and the subsequent loss of both endothelium-dependent and independent
      relaxations. The addition of pravastatin reduced the lucigenin-triggered O(2)(-)
      levels as well as its inhibitory effects on acetylcholine- and sodium
      nitroprusside-dependent responses. These effects were not counteracted by
      mevalonic acid, further supporting the idea that the effects of pravastatin do
      not entail alterations in cholesterol biosynthesis. In conclusion, this study can
      contribute to elucidate the mechanism responsible for the antioxidant activity of
      pravastatin, and describes relationship between a scavenger effect of pravastatin
      and the improvement of vascular reactivity.

PMID- 20044991
TI  - The effect of 17 beta-estradiol on intracellular calcium homeostasis in human
      endothelial cells.
AB  - The cardiovascular effects of estrogen are mediated in part by augmenting the
      function of endothelial nitric oxide synthase. Endothelial nitric oxide synthase
      activity is dependent on many cofactors including Ca(2+). Hence, we investigated
      the effect of chronic 17 beta-estradiol treatment on the intracellular Ca(2+)
      concentration and endothelial nitric oxide synthase protein expression in the
      human endothelial cell line, EA.hy926, using spectrofluorometry and Western blot,
      respectively. Inhibiting the sarco(endo)plasmic reticulum Ca(2+) ATPase with
      thapsigargin caused an increase in the intracellular Ca(2+) concentration, which
      was higher in chronically 17 beta-estradiol-treated (1muM, 24h) cells loaded with
      Fura-2-acetoxymethyl ester compared to vehicle-treated cells, suggesting a higher
      endoplasmic reticulum Ca(2+) content in 17 beta-estradiol-treated cells. An
      enhanced Ca(2+) influx pathway in chronically 17 beta-estradiol-treated cells was
      also observed. In addition, 17 beta-estradiol-treated cells expressed higher
      levels of endothelial nitric oxide synthase protein in comparison to vehicle
      treated cells. The chronic effect of 17 beta-estradiol on Ca(2+) homeostasis and
      endothelial nitric oxide synthase expression was attenuated with the nonselective
      estrogen receptor inhibitor, ICI 182,780 (10muM, 7alpha, 17beta-[9-[(4,4,5,5,5
      Pentafluoropentyl)sulfinyl]nonyl] estra-1,3,5(10)-triene-3,17-diol). Furthermore,
      analysis of the thapsigargin-evoked Ca(2+) response in chronically 17 beta
      estradiol-treated estrogen receptor alpha-knockdown cells showed no significant
      difference in Ca(2+) response compared to vehicle-treated estrogen receptor alpha
      knockdown cells, indicating that the regulation of Ca(2+) homeostasis by 17 beta
      estradiol is mediated through an estrogen receptor alpha-dependent pathway. These
      data revealed an estrogen receptor alpha-dependent modulation of Ca(2+)
      homeostasis accompanying the enhancement of endothelial nitric oxide synthase
      expression in 17 beta-estradiol-treated human endothelial cells.

PMID- 20044992
TI  - Overcoming remyelination failure in multiple sclerosis and other myelin
      disorders.
AB  - Protecting axons from degeneration represents a major unmet need in the treatment
      of myelin disorders and especially the currently untreatable secondary
      progressive stages of multiple sclerosis (MS). Several lines of evidence indicate
      that ensuring myelin sheaths are restored to demyelinated axons, the regenerative
      process of remyelination, represents one of the most effective means of achieving
      axonal protection. Remyelination can occur as a highly effective spontaneous
      regenerative process following demyelination. However, for reasons that have not
      been fully understood, this process is often incomplete or fails in MS.
      Recognizing the reasons for remyelination failure and hence identifying
      therapeutic targets will depend on detailed histopathological studies of myelin
      disorders and a detailed understanding of the molecular mechanisms regulating
      remyelination. Pathology studies have revealed that chronically demyelinated
      lesions in MS often fail to repair because of a failure of differentiation of the
      precursor cell responsible for remyelination rather than a failure of their
      recruitment. In this article we review three mechanisms by which differentiation
      of precursor cells into remyelinating oligodendrocytes are regulated-the Notch
      pathway, the Wnt pathway and the pathways activated by inhibitor of
      differentiation in myelin debris-and indicate how these might be
      pharmacologically targeted to overcome remyelination failure.

PMID- 20044994
TI  - Antibody-mediated impairment and homeostatic plasticity of autonomic ganglionic
      synaptic transmission.
AB  - Antibodies against ganglionic acetylcholine receptors (AChR) are implicated as
      the cause of autoimmune autonomic ganglionopathy (AAG). To characterize
      ganglionic neurotransmission in an animal model of AAG, evoked and spontaneous
      excitatory post-synaptic potentials (EPSP) were recorded from neurons in isolated
      mouse superior cervical ganglia (SCG). In vitro exposure of ganglia to IgG from
      AAG patients progressively inhibited synaptic transmission. After passive
      transfer of antibody to mice, evoked EPSP amplitude decreased, and some neurons
      showed no synaptic responses. EPSP amplitude recovered by day 7 despite
      persistence of ganglionic AChR antibody in the mouse serum. There was a more
      persistent (at least 14-day) reduction in miniature EPSP amplitude consistent
      with antibody-mediated reduction in post-synaptic AChR. Although the quantal size
      was reduced, a progressive increase in the frequency of spontaneous synaptic
      events occurred, suggesting a compensatory increase in presynaptic efficacy. The
      quantal size returned to baseline by 21 days while the frequency remained
      increased for at least four weeks. Ganglionic AChR antibodies cause an impairment
      of autonomic ganglionic synaptic transmission. Homeostatic plasticity in
      autonomic neurotransmission could help explain the spontaneous clinical recovery
      seen in some AAG patients and may also play an important role in regulating
      normal autonomic reflexes.

PMID- 20044993
TI  - Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral
      sclerosis and other neurodegenerative disorders.
AB  - Neurodegenerative diseases, Alzheimer's and Parkinson's diseases, and amyotrophic
      lateral sclerosis (ALS) are progressive and devastating disorders of the nervous
      system without cure. Although a number of distinct, but not mutually exclusive,
      mechanisms can affect disease pathogenesis, neuroinflammation stands in common.
      Neuroinflammatory responses occur as a consequence of oxidative and excitotoxic
      neuronal damage, mitochondrial dysfunction, and protein aggregation. Thus, it is
      believed drugs that modulate inflammation may combat disease progression. Such
      strategies include those commented on in the report by Arie Neymotin et al.
      demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in
      the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin et al.,
      2009). While anti-inflammatory interventions may be required, they may not be
      sufficient to positively affect clinical outcomes. The targeting of combinations
      of pathogenic events including clearance of disaggregated proteins together with
      neuroprotective and immune modulatory strategies may all be required to
      facilitate positive therapeutic outcomes. This may include the targeting of both
      innate and adaptive neurotoxic immune responses. This commentary is designed to
      summarize the promises and perils in achieving immunoregulation for brain
      homeostatic responses and inevitable therapeutic gain. Promising new ways to
      optimize immunization schemes and measure their clinical efficacy are discussed
      with a particular focus on ALS.

PMID- 20044995
TI  - CpG methylation and reduced expression of O6-methylguanine DNA methyltransferase
      is associated with Helicobacter pylori infection.
AB  - BACKGROUND & AIMS: The gastric epithelium genome undergoes extensive epigenetic
      alterations during Helicobacter pylori-induced gastritis. Expression of the gene
      encoding the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT)
      might be reduced via hypermethylation of its promoter in patients with H pylori
      gastritis. We characterized expression of MGMT and its epigenetic regulation via
      CpG methylation in gastric tissue from patients with H pylori gastritis and
      investigated the effects of H pylori infection eradication on MGMT expression.
      METHODS: Gastric biopsy samples were collected from patients with H pylori
      gastritis before and after eradication and from H pylori-negative control
      subjects. AGS cells were cocultured with H pylori to study the effects of H
      pylori infection on MGMT RNA, protein expression, and CpG methylation. RESULTS:
      CpG methylation of MGMT was more frequent in the gastric mucosa of patients with
      H pylori gastritis (69.7%) than in those without (28.6%, P = .022). MGMT
      methylation was significantly reduced after H pylori eradication (from 70% to 48%
      of cases, P = .039), and mean levels of CpG methylation decreased from 12.6% to
      5.7% (P = .025), increasing MGMT expression. MGMT methylation was significantly
      associated with CagA-positive H pylori (P = .035). H pylori reduced MGMT protein
      and RNA levels and induced MGMT CpG methylation in gastric AGS cells.
      CONCLUSIONS: H pylori gastritis, particularly in patients infected with H pylori
      CagA-positive strains, is associated with hypermethylation of MGMT and reduced
      levels of MGMT in the gastric epithelium. MGMT promoter methylation is partially
      reversible after eradication of H pylori infection. These data indicate that DNA
      repair is disrupted during H pylori gastritis, increasing mutagenesis in H pylori
      infected gastric mucosa.

PMID- 20044996
TI  - In vitro-derived alternatively activated macrophages reduce colonic inflammation
      in mice.
AB  - BACKGROUND & AIMS: Infection with the rat tapeworm Hymenolepis diminuta reduces
      the severity of dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice.
      Infection with H. diminuta increases colonic expression of arginase-1 and found
      in inflammatory zone 1 (FIZZ1), markers of alternatively activated macrophages
      (AAMs). We investigated whether AAMs have anticolitic effects. METHODS: Normal or
      macrophage-depleted Balb/c mice were infected with H. diminuta; some mice were
      given DNBS, and the severity of colitis was assessed by disease activity scores,
      myeloperoxidase activity, and histologic examination. AAMs were also
      differentiated in vitro, given to mice by intraperitoneal or intravenous
      injection, and the effects on DNBS-induced colitis were determined. Numbers of
      AAMs were assessed in biopsy specimens from patients with Crohn's disease.
      RESULTS: Depletion of intestinal macrophages using clodronate-liposomes prevented
      the anticolitic effect of infection with H. diminuta. Injection of AAMs, but not
      classically activated macrophages, significantly reduced the severity of DNBS
      induced colitis. The AAM-induced, anticolitic effect was accompanied by increased
      interleukin (IL)-10 production from mitogen-stimulated spleen cells; in vivo
      neutralization of IL-10 partially reduced the effects of AAM transfer. Patients
      with active CD had reduced numbers of CD68(+)CD206(+) macrophages (which indicate
      AAM), whereas biopsy specimens from patients with inactive CD had increased
      numbers of these cells. CONCLUSIONS: Analysis of the H. diminuta-murine DNBS
      system identified the AAM, which, when administered to mice, significantly
      reduced DNBS-induced colitis. The ability to derive AAMs from patients' blood
      suggests that adoptive transfer of these cells could be a novel approach to
      inflammatory bowel disease.

PMID- 20044997
TI  - Biofeedback is superior to electrogalvanic stimulation and massage for treatment
      of levator ani syndrome.
AB  - BACKGROUND & AIMS: Levator ani syndrome (LAS) might be treated using biofeedback
      to teach pelvic floor relaxation, electrogalvanic stimulation (EGS), or massage
      of levator muscles. We performed a prospective, randomized controlled trial to
      compare the effectiveness of these techniques and assess physiologic mechanisms
      for treatment. METHODS: Inclusion criteria were Rome II symptoms plus weekly
      pain. Patients were categorized as "highly likely" to have LAS if they reported
      tenderness with traction on the levator muscles or as "possible" LAS if they did
      not. All 157 patients received 9 sessions including psychologic counseling plus
      biofeedback, EGS, or massage. Outcomes were reassessed at 1, 3, 6, and 12 months.
      RESULTS: Among patients with "highly likely" LAS, adequate relief was reported by
      87% for biofeedback, 45% for EGS, and 22% for massage. Pain days per month
      decreased from 14.7 at baseline to 3.3 after biofeedback, 8.9 after EGS, and 13.3
      after massage. Pain intensity decreased from 6.8 (0-10 scale) at baseline to 1.8
      after biofeedback, 4.7 after EGS, and 6.0 after massage. Improvements were
      maintained for 12 months. Patients with only a "possible" diagnosis of LAS did
      not benefit from any treatment. Biofeedback and EGS improved LAS by increasing
      the ability to relax pelvic floor muscles and evacuate a water-filled balloon and
      by reducing the urge and pain thresholds. CONCLUSIONS: Biofeedback is the most
      effective of these treatments, and EGS is somewhat effective. Only patients with
      tenderness on rectal examination benefit. The pathophysiology of LAS is similar
      to that of dyssynergic defecation.

PMID- 20044998
TI  - Genetic risk factors for post-infectious irritable bowel syndrome following a
      waterborne outbreak of gastroenteritis.
AB  - BACKGROUND & AIMS: Acute gastroenteritis is the strongest risk factor for
      irritable bowel syndrome (IBS). In May 2000, >2300 residents of Walkerton,
      Ontario, developed gastroenteritis from microbial contamination of the municipal
      water supply; a longitudinal study found that >36.2% of these developed IBS. We
      used this cohort to study genetic susceptibility to post-infectious (PI)-IBS.
      METHODS: We screened 79 functional variants of genes with products involved in
      serotoninergic pathways, intestinal epithelial barrier function, and innate
      immunity and performed fine mapping in regions of interest. We compared data from
      Walkerton residents who developed gastroenteritis and reported PI-IBS 2 to 3
      years after the outbreak (n = 228, cases) with data from residents who developed
      gastroenteritis but did not develop PI-IBS (n = 581, controls). RESULTS: Four
      variants were associated with PI-IBS, although the association was not
      significant after correction for the total number of single nucleotide
      polymorphisms. Two were located in TLR9, which encodes a pattern recognition
      receptor (rs352139, P545P; P = .0059 and rs5743836, -T1237C; P = .0250; r(2) <
      0.14); 1 was in CDH1, which encodes a tight junction protein (rs16260, -C160A; P
      = .0352); and 1 was in IL6, which encodes a cytokine (rs1800795, -G174C; P =
      .0420). Denser mapping of these 3 regions revealed 1 novel association in IL6
      (rs2069861; P = .0069) and 14 associations that could be accounted for by linkage
      disequilibrium with the 4 original variants. The TLR9, IL6, and CDH1 variants all
      persisted as independent risk factors for PI-IBS when controlling for previously
      identified clinical risk factors. CONCLUSION: This is the first descriptive study
      to assess potential genetic determinants of PI-IBS. Genes that encode proteins
      involved in epithelial cell barrier function and the innate immune response to
      enteric bacteria are associated with development of IBS following acute
      gastroenteritis.

PMID- 20044999
TI  - Ghrelin's quick inhibition of androgen-dependent behaviors of male house mice
      (Mus musculus).
AB  - Ghrelin is a peptide hormone released by the stomach that stimulates hunger.
      Ghrelin also suppresses reproductive physiology by inhibiting the HPG axis.
      However, to our knowledge, our results are the first to demonstrate ghrelin's
      quick suppression of sex-hormone-regulated behaviors. In experiment 1, 2
      orexigenic i.p. ghrelin injections (0.165 mg/kg and 0.33 mg/kg) suppressed male
      courtship behavior (ultrasonic calling to a female) and intermale aggression
      (latency to attack a stimulus male) 20 min following administration. Experiment 2
      (examining only the 0.33 mg/kg dose ) replicated ghrelin's suppression of
      ultrasonic calling and intermale aggression; however, a third behavior,
      preference for volatile female odors (20 min following administration), was not
      significantly inhibited. In experiment 2, ghrelin treatment did not affect
      general locomotor activity (distance traveled 20 min following injection) or
      seminal vesicle weight (measured 5 days after completing ghrelin injections). We
      hypothesize that ghrelin's quick suppression of male aggression and ultrasonic
      mating calls was mediated through its effects on the brain (rather than
      indirectly through inhibition of the HPG axis).

PMID- 20045000
TI  - Early removal of alternatively activated macrophages leads to Taenia crassiceps
      cysticercosis clearance in vivo.
AB  - To determine the role of alternatively activated macrophages in modulating the
      outcome of experimental cysticercosis caused by Taenia crassiceps, we
      investigated the effect of removal of alternatively activated macrophage by
      injecting clodronate-loaded liposomes into susceptible BALB/c mice. Following T.
      crassiceps infection, mice receiving PBS-loaded liposomes developed a dominant
      Th2-type response associated with the presence of alternatively activated
      macrophages together with antigen-specific hyporesponsiveness and high parasite
      burden. In contrast, similarly infected mice treated with clodronate-loaded
      liposomes mounted a mixed Th1/Th2-type response, reversed antigen-specific
      hyporesponsiveness and did not carry notable alternatively activated macrophage
      populations. These factors were associated with increased resistance to T.
      crassiceps cysticercosis. Interestingly, early AAM phi depletion was enough to
      limit parasite growth. However, if macrophages were depleted late in the
      infection, no effect on parasite burden was observed. These findings demonstrate
      that alternatively activated macrophages play a critical role in mediating
      susceptibility to experimental cysticercosis in which their early recruitment may
      favor parasite survival.

PMID- 20045001
TI  - Thermal response and reversibility of prolonged larval diapause in the chestnut
      weevil, Curculio sikkimensis.
AB  - Curculio sikkimensis undergoes prolonged larval diapause that is terminated by
      chilling and warming cycles. To examine the effects of warming temperatures and
      their duration on diapause termination, we exposed diapause larvae that had not
      been reactivated after chilling at 5 degrees C to 20 or 25 degrees C and chilled
      them again before incubation at 20 degrees C. With increasing warming duration at
      20 degrees C, diapause termination after chilling increased and shorter chilling
      durations became effective. In contrast, few or no larvae warmed at 25 degrees C
      terminated diapause after chilling, irrespective of the warming duration. To
      investigate the effect of warming temperature on diapause intensity, larvae with
      diapause weakened by initial incubation at 20 degrees C after the first chilling
      were subsequently incubated at 15, 20, or 25 degrees C, then chilled at 5 degrees
      C before incubation at 20 degrees C. Diapause termination increased significantly
      after the larvae were treated at 15 or 20 degrees C but decreased significantly
      after they were treated at 25 degrees C. The intensification of prolonged
      diapause at 25 degrees C was reversed when the larvae were transferred to 20
      degrees C. Diapause intensity in C. sikkimensis therefore decreases at 20 degrees
      C, increases at 25 degrees C, and can be reversed by alternately exposing
      diapause larvae to 20 and 25 degrees C. In C. sikkimensis, prolonged diapause
      does not always proceed in one direction, and its intensity fluctuates in
      response to ambient temperature conditions.

PMID- 20045002
TI  - Group size effect on worker juvenile hormone titers and soldier differentiation
      in Formosan subterranean termite.
AB  - In a finite environment, population growth can lead to crowding, increased
      densities and stress. Termites live in highly organized societies and densities
      can increase astronomically as colonies grow. However, little is known about
      juvenile hormone (JH) changes in these insects as numbers increase, despite the
      fact that JH is a critical caste regulator in this insect. Using Formosan
      subterranean termites as a model, we evaluated minimum group size requirements
      for soldier differentiation and the effect of density (50, 100, 500, and 1000
      individuals/experimental unit) on worker JH titers either with or without initial
      soldiers being present. The minimum group size investigation indicated that
      groups initiated with 5 workers were insufficient for soldier differentiation.
      Soldiers were produced in groups initiated with 10 or more workers. As density
      increased from 50 to 1000 individuals per experimental unit, worker JH levels
      were elevated. Presence of soldiers lessened the effect of density on rising
      worker JH titers, indicating that soldiers have the ability to down-regulate
      worker JH. The study provides direct evidence of a population density effect on
      JH in eusocial insects and sheds light on understanding of the regulatory
      mechanisms associated with termite soldier caste differentiation.

PMID- 20045003
TI  - A new twist in cardiac muscle: dislocated and helicoid arrangements of
      myofibrillar z-disks in mammalian ventricular myocytes.
AB  - Using deconvolved confocal microscopy of fluorescently labeled markers for z
      disks, t-tubules and ryanodine receptors, we have examined sarcomere organization
      in cardiac myocytes from rat, rabbit and human. We show that sarcomeres exhibit
      dislocations in registration and occasionally more complex helicoidal topology.
      This organization was present at both slack ( approximately 1.8 microm) and long
      sarcomere lengths ( approximately 2.2 microm). Misregistrations in z-disks
      persisted over 15-20 sarcomere lengths and appeared to arise primarily from
      variations in fiber direction; particularly as myofibrils pass around nuclei. In
      addition, myofibrils twist along the cell length. T-tubules generally follow the
      sarcomere z-disks although additional elements bridging adjacent myofibrils and
      along the length of the myofibril are present to varying degrees in all cells.
      Ryanodine receptors (the sarcoplasmic reticulum Ca(2+) release channel) are
      generally located within 250 nm of the local plane containing t-tubules and z
      disks, but a small fraction ( approximately 2%) is found on longitudinal elements
      of the t-system between z-disks. The results are discussed with respect to the
      possible role(s) of such complex z-disk organization and z-disk dislocations in
      the maintenance of cell structure and sarcomere assembly. In addition, the non
      planar organization of z-disks may be important in the propagation of local
      Ca(2+) waves which may have a useful role in helping maintain the uniformity of
      sarcomere activation in the presence of t-tubule remodeling.

PMID- 20045004
TI  - Glycolytic network restructuring integral to the energetics of embryonic stem
      cell cardiac differentiation.
AB  - Decoding of the bioenergetic signature underlying embryonic stem cell cardiac
      differentiation has revealed a mandatory transformation of the metabolic
      infrastructure with prominent mitochondrial network expansion and a distinctive
      switch from glycolysis to oxidative phosphorylation. Here, we demonstrate that
      despite reduction in total glycolytic capacity, stem cell cardiogenesis engages a
      significant transcriptome, proteome, as well as enzymatic and topological
      rearrangement in the proximal, medial, and distal modules of the glycolytic
      pathway. Glycolytic restructuring was manifested by a shift in hexokinase (Hk)
      isoforms from Hk-2 to cardiac Hk-1, with intracellular and intermyofibrillar
      localization mapping mitochondrial network arrangement. Moreover, upregulation of
      cardiac-specific enolase 3, phosphofructokinase, and phosphoglucomutase and a
      marked increase in glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
      phosphotransfer activity, along with apparent post-translational modifications of
      GAPDH and phosphoglycerate kinase, were all distinctive for derived
      cardiomyocytes compared to the embryonic stem cell source. Lactate dehydrogenase
      (LDH) isoforms evolved towards LDH-2 and LDH-3, containing higher proportions of
      heart-specific subunits, and pyruvate dehydrogenase isoforms rearranged between
      E1alpha and E1beta, transitions favorable for substrate oxidation in
      mitochondria. Concomitantly, transcript levels of fetal pyruvate kinase isoform
      M2, aldolase 3, and transketolase, which shunt the glycolytic with pentose
      phosphate pathways, were reduced. Collectively, changes in glycolytic pathway
      modules indicate active redeployment, which would facilitate connectivity of the
      expanding mitochondrial network with ATP utilization sites. Thus, the delineated
      developmental dynamics of the glycolytic phosphotransfer network is integral to
      the remodeling of cellular energetic infrastructure underlying stem cell
      cardiogenesis.

PMID- 20045005
TI  - Tumor necrosis factor-alpha produced in cardiomyocytes mediates a predominant
      myocardial inflammatory response to stretch in early volume overload.
AB  - Acute stretch caused by volume overload (VO) of aorto-caval fistula (ACF) induces
      a variety of myocardial responses including mast cell accumulation, matrix
      metalloproteinase (MMP) activation, and collagen degradation, all of which are
      critical in dictating long-term left ventricle (LV) outcome to VO. Meanwhile,
      these responses can be part of myocardial inflammation dictated by tumor necrosis
      factor-alpha (TNF-alpha), which is elevated after acute ACF. However, it is
      unknown whether TNF-alpha mediates a major myocardial inflammatory response to
      stretch in early VO. In 24-h ACF and sham rats, microarray gene expression
      profiling and subsequent Ingenuity Pathway Analysis identified a predominant
      inflammatory response and a gene network of biologically interactive genes
      strongly linked to TNF-alpha. Western blot demonstrated increased local
      production of TNF-alpha in the LV (1.71- and 1.66-fold in pro- and active-TNF
      alpha over control, respectively, P<0.05) and cardiomyocytes (2- and 4-fold in
      pro- and active-TNF-alpha over control, respectively, P<0.05). TNF-alpha
      neutralization with infliximab (5.5 mg/kg) attenuated the myocardial inflammatory
      response to acute VO, as indicated by inhibition of inflammatory gene
      upregulation, myocardial infiltration (total CD45+ cells, mast cells, and
      neutrophils), MMP-2 activation, collagen degradation, and cardiac cell apoptosis,
      without improving LV remodeling and function. These results indicate that TNF
      alpha produced by cardiomyocytes mediates a predominant inflammatory response to
      stretch in the early VO in the ACF rat, suggesting an important role of TNF-alpha
      in initiating pathophysiological response of myocardium to VO.

PMID- 20045006
TI  - Effect of prolonged administration of bovine lactoferrin in neuropathic pain:
      involvement of opioid receptors, nitric oxide and TNF-alpha.
AB  - AIMS: This study aimed to investigate the effect of prolonged administration of
      bovine milk lactoferrin (bLF) on hyperalgesia and allodynia in a rat model of
      neuropathic pain and to determine the involvement of c-Fos, TNF-alpha, nitric
      oxide and opioidergic systems in this effect. MAIN METHODS: Neuropathic pain was
      induced in rats by loose ligation of the right sciatic nerve and evaluated by
      tests measuring the mechanical and thermal hyperalgesia and allodynia. bLF (50,
      100, and 200mg/kg) alone or in combination with opioidergic antagonists were
      administered intraperitoneally to the rats with neuropathic pain. c-Fos and NADPH
      d immunocytochemistry and Western blotting for TNF-alpha, iNOS and nNOS were
      performed in the lumbar spinal cord of rats. Plasma TNF-alpha levels were
      determined with ELISA. KEY FINDINGS: Prolonged, but not single, administration of
      bLF produced antihyperalgesic and antiallodynic effects in neuropathic rats.
      Pretreatment with opioidergic antagonists significantly decreased this effect.
      Prolonged administration of bLF decreased c-Fos and NADPH-d immunoreactivity and
      TNF-alpha and iNOS expressions at 50 and 100mg/kg and nNOS expression at 100mg/kg
      in the lumbar spinal cord of neuropathic rats. Plasma TNF-alpha levels remained
      unchanged after bLF treatment. SIGNIFICANCE: Prolonged administration of bLF
      exerts antihyperalgesic and antiallodynic effect in neuropathic rats; down
      regulation of both TNF-alpha and iNOS expressions and potentiation of opioidergic
      system in the lumbar spinal cord can contribute to this effect.

PMID- 20045007
TI  - Synergistic effects of FGF-2 and PDGF-BB on angiogenesis and muscle regeneration
      in rabbit hindlimb ischemia model.
AB  - Combinatorial strategy has been used in therapeutic angiogenesis in animal models
      of peripheral arterial disease (PAD) and coronary artery disease for decades.
      Previous studies have shown that basic fibroblast growth factor (FGF-2) and
      platelet-derived growth factor BB (PDGF-BB) proteins together establish
      functional and stable vascular networks on mouse corneal and also in animal model
      of hindlimb ischemia. However, the short half life of protein by single injection
      is not sufficient to achieve effective dosage, repeated and prolonged injection
      causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF
      BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in
      rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and
      PDGF-BB naked DNA together resulted in greater increases in capillary growth,
      collateral formation and popliteal blood flow compared with control and single
      gene delivery. Our data provided novel evidence of beneficial effects of DNA
      based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings
      reveal an alternative therapeutic approach in the treatment of ischemic diseases
      and even in muscular disorders.

PMID- 20045008
TI  - Central interleukin-10 attenuates lipopolysaccharide-induced changes in food
      intake, energy expenditure and hypothalamic Fos expression.
AB  - Lipopolysaccharide (LPS) is often used to mimic acute infection and induces
      hypophagia, the selective partitioning of fat for energy, and fever. Interleukin
      10 (IL-10) is an anti-inflammatory cytokine expressed in the brain which
      attenuates LPS-induced hypophagia; however the potential sites of interaction
      within the brain have not been investigated. Hypothalamic orexin (ORX) and
      melanin-concentrating hormone (MCH) regulate energy expenditure and food intake
      although the regulation of these neuropeptides through the interactions between
      central IL-10 and the inflammatory consequences of peripheral LPS have not been
      investigated. The present study in the rat investigated during the dark phase of
      the light-dark cycle the ability of central IL-10 (250 ng, i.c.v.) to attenuate
      the changes in food intake, energy substrate partitioning, and central Fos
      expression within the hypothalamus to peripheral LPS (100 microg/kg, i.p.); Fos
      expression changes specifically within ORX and MCH neurons were also
      investigated. Central IL-10 attenuated the peripheral LPS-induced hypophagia,
      reduction in motor activity, fever and reduction in respiratory exchange ratio.
      Central IL-10 also attenuated peripheral LPS-induced increases in Fos expression
      within ORX neurons and decreases in Fos expression within unidentified cells of
      the caudal arcuate nucleus. In contrast, both IL-10 and LPS injection
      independently decreased Fos expression within MCH neurons. The present study
      provides further insight into the interactions within the brain between the anti
      inflammatory cytokine IL-10, the inflammatory consequences of LPS, and
      neuropeptides known to regulate energy expenditure and food intake.

PMID- 20045009
TI  - Alcohol and cardiovascular health.
AB  - The substantial medical risks of heavy alcohol drinking as well as the probable
      existence of a less harmful or safe drinking limit have been evident for
      centuries. Modern epidemiology studies suggest lowered risk of morbidity and
      mortality among lighter drinkers. Thus, defining "heavy" drinking as > or =3
      standard drinks per day, the alcohol-mortality relationship is a J-curve with
      risk highest for heavy drinkers, lowest for light drinkers and intermediate for
      abstainers. A number of non-cardiovascular and cardiovascular problems contribute
      to the increased mortality risk of heavier drinkers. The lower risk of light
      drinkers is due mostly to lower risk of the most common cardiovascular condition,
      coronary heart disease (CHD). These disparate relationships of alcoholic drinking
      to various cardiovascular and non-cardiovascular conditions constitute a modern
      concept of alcohol and health. Increased cardiovascular risks of heavy drinking
      include: (1) alcoholic cardiomyopathy, (2) systemic hypertension (high blood
      pressure), (3) heart rhythm disturbances, and (4) hemorrhagic stroke. Lighter
      drinking is not clearly related to increased risk of any cardiovascular condition
      and, in observational studies, is related to lower risk of CHD, ischemic stroke,
      and diabetes mellitus. A protective hypothesis for CHD is supported by evidence
      for plausible biological mechanisms attributable to ethyl alcohol. International
      comparisons and some prospective study data suggest that wine is more protective
      against CHD than liquor or beer. Possible non-alcohol beneficial components in
      wine (especially red) support possible extra protection by wine, but a healthier
      pattern of drinking or more favorable risk traits in wine drinkers may be
      involved.

PMID- 20045010
TI  - Sex differences in the effects of cocaine abuse across the life span.
AB  - Cocaine alters brain function from the early days of development throughout the
      entire life of an individual. Since the first preclinical research on cocaine
      sensitization was published, sex differences in response to the drug in adult
      rats have been noted. With the appearance of reports on "crack babies" during the
      1980s, sex differences in response to prenatal (developmental) exposure have been
      identified in both clinical and preclinical reports. Cocaine administered during
      early development in the rat produces wide-spread alterations in function which
      depend on the timing of drug administration as well as the sex of the animal. In
      males, the response patterns following postnatal days (PND) 11-20 cocaine
      administration (equivalent to the late prenatal period in humans) are quite
      similar to those seen following prenatal exposure (equivalent to the first half
      of pregnancy in humans). There is a general decrease in dopaminergic (DA) markers
      and reactivity perhaps due to the uncoupling of the D1 receptor from its second
      messenger system. While similar changes in D1 uncoupling are seen in females,
      behavioral and metabolic responses to drug challenges generally show increases in
      DA responsivity (except adolescents) perhaps due to the activational effects of
      estrogen and/or decreases in serotonin (5-HT) mediated regulation of DA function.
      We have found that a significant factor in the hyper-responsivity of the female
      is the role of the testing environment and the responses to stress which can
      obscure underlying neurochemical dysregulation. Whether parallel factors are
      operational in adult males and females is currently under investigation.

PMID- 20045012
TI  - Acute exercise activates local bioactive androgen metabolism in skeletal muscle.
AB  - Androgens, such as testosterone, play important roles in regulation of diverse
      physiological process of target tissues. Recently, we reported that steroidogenic
      enzymes exist in skeletal muscle and regulate local production of testosterone in
      response to exercise. Testosterone is transformed into a bioactive androgen
      metabolite, dihydrotestosterone (DHT) by 5alpha-reductase. However, it is unclear
      whether exercise stimulates local bioactive androgen metabolism in the skeletal
      muscle in both sexes. In the present study, we examined sex differences in the
      levels of dehydroepiandrosterone (DHEA), free testosterone, DHT, and
      steroidogenesis-related enzymes 5alpha-reductase and androgen receptor (AR) in
      rat's skeletal muscle before and after a single bout of exercise. Basal muscular
      free testosterone and DHT levels were higher in males than females, whereas the
      levels of DHEA did not differ between the sexes. Muscular DHEA, free
      testosterone, and DHT levels were increased in both sexes after the exercise.
      There were no differences of 5alpha-reductase and AR transcripts and proteins
      between the sexes, and the expression of 5alpha-reductase was significantly
      increased in both sexes after the exercise. Finally, the expression of AR was
      significantly higher in female rats, but not in males after the exercise. These
      data suggest that acute exercise enhances the local bioactive androgen metabolism
      in the skeletal muscle of both sexes.

PMID- 20045013
TI  - Biomarkers of acute respiratory allergen exposure: screening for sensitization
      potential.
AB  - Effective hazard screening will require the development of high-throughput or in
      vitro assays for the identification of potential sensitizers. The goal of this
      preliminary study was to identify potential biomarkers that differentiate the
      response to allergens vs non-allergens following an acute exposure in naive
      individuals. Female BALB/c mice received a single intratracheal aspiration
      exposure to Metarhizium anisopliae crude antigen (MACA) or bovine serum albumin
      (BSA) in Hank's Balanced Salt Solution (HBSS) or HBSS alone. Mice were terminated
      after 1, 3, 6, 12, 18 and 24 h. Bronchoalveolar lavage fluid (BALF) was evaluated
      to determine total and differential cellularity, total protein concentration and
      LDH activity. RNA was isolated from lung tissue for microarray analysis and qRT
      PCR. MACA administration induced a rapid increase in BALF neutrophils,
      lymphocytes, eosinophils and total protein compared to BSA or HBSS. Microarray
      analysis demonstrated differential expression of genes involved in cytokine
      production, signaling, inflammatory cell recruitment, adhesion and activation in
      3 and 12 h MACA-treated samples compared to BSA or HBSS. Further analyses allowed
      identification of approximately 100 candidate biomarker genes. Eleven genes were
      selected for further assessment by qRT-PCR. Of these, 6 demonstrated persistently
      increased expression (Ccl17, Ccl22, Ccl7, Cxcl10, Cxcl2, Saa1), while C3ar1
      increased from 6-24 h. In conclusion, a single respiratory exposure of mice to an
      allergenic mold extract induces an inflammatory response which is distinct in
      phenotype and gene transcription from the response to a control protein. Further
      validation of these biomarkers with additional allergens and irritants is needed.
      These biomarkers may facilitate improvements in screening methods.

PMID- 20045011
TI  - RSK in tumorigenesis: connections to steroid signaling.
AB  - The Ser/Thr kinase family, RSK, has been implicated in numerous types of hormone
      dependent and -independent cancers. However, there has been little consideration
      of RSKs as downstream mediators of steroid hormone non-genomic effects or of
      their ability to facilitate steroid receptor-mediated gene expression. Steroid
      hormone signaling can directly stimulate the MEK/ERK/RSK pathway to regulate
      cellular proliferation and survival in transformed cells. To date, multiple
      mechanisms of RSK and steroid hormone receptor-mediated proliferation/survival
      have been elucidated. For example, RSK enhances proliferation of breast and
      prostate cancer cells via its ability to control the levels of the estrogen
      receptor co-activator, cyclin D1. While in lung and other tumors RSK may control
      apoptosis via estrogen-mediated regulation of mitochondrial integrity. Thus the
      RSKs could be important anti-cancer therapeutic targets in many different
      transformed tissues. The recent discovery of RSK-specific inhibitors will advance
      our current understanding of RSK in transformation and drive these studies into
      animal and clinical models. In this review we explore the mechanisms associated
      with RSK in tumorigenesis and their relationship to steroid hormone signaling.

PMID- 20045014
TI  - Dietary administration of sodium arsenite to rats: relations between dose and
      urinary concentrations of methylated and thio-metabolites and effects on the rat
      urinary bladder epithelium.
AB  - Based on epidemiological data, chronic exposure to high levels of inorganic
      arsenic in drinking water is carcinogenic to humans, inducing skin, urinary
      bladder and lung tumors. In vivo, inorganic arsenic is metabolized to organic
      methylated arsenicals including the highly toxic dimethylarsinous acid (DMA(III))
      and monomethylarsonous acid (MMA(III)). Short-term treatment of rats with 100
      microg/g trivalent arsenic (As(III)) as sodium arsenite in the diet or in
      drinking water induced cytotoxicity and necrosis of the urothelial superficial
      layer, with increased cell proliferation and hyperplasia. The objectives of this
      study were to determine if these arsenic-induced urothelial effects are dose
      responsive, the dose of arsenic at which urothelial effects are not detected, and
      the urinary concentrations of the arsenical metabolites. We treated female F344
      rats for 5 weeks with sodium arsenite at dietary doses of 0, 1, 10, 25, 50, and
      100 ppm. Cytotoxicity, cell proliferation and hyperplasia of urothelial
      superficial cells were increased in a dose-responsive manner, with maximum
      effects found at 50 ppm As(III). There were no effects at 1 ppm As(III). The main
      urinary arsenical in As(III)-treated rats was the organic arsenical
      dimethylarsinic acid (DMA(V)). The thio-metabolites dimethylmonothioarsinic acid
      (DMMTA(V)) and monomethylmonothioarsinic acid (MMMTA(V)) were also found in the
      urine of As(III)-treated rats. The LC(50) concentrations of DMMTA(V) for rat and
      human urothelial cells in vitro were similar to trivalent oxygen-containing
      arsenicals. These data suggest that dietary As(III)-induced urothelial
      cytotoxicity and proliferation are dose responsive, and the urothelial effects
      have a threshold corresponding to the urinary excretion of measurable reactive
      metabolites.

PMID- 20045015
TI  - Regulatory aspects of oncology drug safety evaluation: past practice, current
      issues, and the challenge of new drugs.
AB  - The drug development of new anti-cancer agents is streamlined in response to the
      urgency of bringing effective drugs to market for patients with limited life
      expectancy. FDA's regulation of oncology drugs has evolved from the practices set
      forth in Arnold Lehman's seminal work published in the 1950s through the current
      drafting of a new International Conference on Harmonization of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety
      guidance for anti-cancer drug nonclinical evaluations. The ICH combines the
      efforts of the regulatory authorities of Europe, Japan, and the United States and
      the pharmaceutical industry from these three regions to streamline the scientific
      and technical aspects of drug development. The recent development of new oncology
      drug classes with novel mechanisms of action has improved survival rates for some
      cancers but also brings new challenges for safety evaluation. Here we present the
      legacy of Lehman and colleagues in the context of past and present oncology drug
      development practices and focus on some of the current issues at the center of an
      evolving harmonization process that will generate a new safety guidance for
      oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate
      oncology drug development on a global scale by standardizing regional safety
      requirements.

PMID- 20045016
TI  - Drug interactions evaluation: an integrated part of risk assessment of
      therapeutics.
AB  - Pharmacokinetic drug interactions can lead to serious adverse events or decreased
      drug efficacy. The evaluation of a new molecular entity's (NME's) drug-drug
      interaction potential is an integral part of risk assessment during drug
      development and regulatory review. Alteration of activities of enzymes or
      transporters involved in the absorption, distribution, metabolism, or excretion
      of a new molecular entity by concomitant drugs may alter drug exposure, which can
      impact response (safety or efficacy). The recent Food and Drug Administration
      (FDA) draft drug interaction guidance
      (http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
      ces/ucm072101.pdf) highlights the methodologies and criteria that may be used to
      guide drug interaction evaluation by industry and regulatory agencies and to
      construct informative labeling for health practitioner and patients. In addition,
      the Food and Drug Administration established a "Drug Development and Drug
      Interactions" website to provide up-to-date information regarding evaluation of
      drug interactions
      (http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInt
      ractionsLabeling/ucm080499.htm). This review summarizes key elements in the FDA
      drug interaction guidance and new scientific developments that can guide the
      evaluation of drug-drug interactions during the drug development process.

PMID- 20045017
TI  - Dithiocarbamates are teratogenic to developing zebrafish through inhibition of
      lysyl oxidase activity.
AB  - Dithiocarbamates (DTCs) are a class of compounds that are extensively used in
      agriculture as pesticides. As such, humans and wildlife are undoubtedly exposed
      to these chemicals. Although DTCs are thought to be relatively safe due to their
      short half lives, it is well established that they are teratogenic to
      vertebrates, especially to fish. In zebrafish, these teratogenic effects are
      characterized by distorted notochord development and shortened anterior to
      posterior axis. DTCs are known copper (Cu) chelators but this does not fully
      explain the observed teratogenic effects. We show here that DTCs cause
      malformations in zebrafish that highly resemble teratogenic effects observed by
      direct inhibition of a group of cuproenzymes termed lysyl oxidases (LOX).
      Additionally, we demonstrate that partial knockdown of three LOX genes, lox,
      loxl1 and loxl5b, sensitizes the developing embryo to DTC exposure. Finally, we
      show that DTCs directly inhibit zebrafish LOX activity in an ex vivo amine
      oxidase assay. Taken together, these results provide the first evidence that DTC
      induced teratogenic effects are, at least in part, caused by direct inhibition of
      LOX activity.

PMID- 20045018
TI  - Biotransformation of 2,3,3,3-tetrafluoropropene (HFO-1234yf) in rabbits.
AB  - 2,3,3,3-Tetrafluoropropene (HFO-1234yf) is a non-ozone-depleting fluorocarbon
      replacement with a low global warming potential and is developed as refrigerant.
      Due to lethality observed after high concentration inhalation exposures of HFO
      1234yf in a developmental toxicity study with rabbits, the biotransformation of
      HFO-1234yf was investigated in this species. Female New Zealand White rabbits
      were exposed to air containing 2000; 10,000; or 50,000 ppm (n=3/concentration)
      HFO234yf. All inhalation exposures were conducted for 6 h in a dynamic exposure
      chamber. Animals were individually housed in metabolic cages after the end of the
      exposures and urines were collected at 12 h intervals for 60 h. For metabolite
      identification, urine samples were analyzed by (1)H-coupled and (1)H-decoupled
      (19)F-NMR and by LC/MS-MS or GC/MS. Metabolites were identified by (19)F-NMR
      chemical shifts, signal multiplicity, (1)H-(19)F coupling constants and by
      comparison with synthetic reference compounds. In urine samples of rabbits
      exposed to 2000; 10,000; or 50,000 ppm HFO-1234yf, the predominant metabolite was
      N-acetyl-S-(3,3,3-trifluoro-2-hydroxypropanyl)-l-cysteine and accounted for app.
      48% of total (19)F-NMR signal intensities. S-(3,3,3-Trifluoro-2
      hydroxypropanyl)mercaptolactic acid, 3,3,3-trifluoro-1,2-dihydroxypropane, 3,3,3
      trifluoro-2-propanol and inorganic fluoride were also present as urinary
      metabolites. In incubations of rabbit liver S9 fractions containing glutathione,
      NADPH and HFO-1234yf, 3,3,3-trifluoro-1,2-dihydroxypropane, S-(3,3,3-trifluoro-2
      hydroxypropanyl)glutathione, 3,3,3-trifluoro-2-propanol and inorganic fluoride
      were identified as metabolites of HFO-1234yf by (19)F-NMR. The quantity of
      recovered metabolites in urine suggest a low extent (<0.1% of dose received) of
      biotransformation of HFO-1234yf in rabbits, and 95% of all metabolites were
      excreted within 12 h after the end of the exposures (t(1/2) app. 9.5 h). The
      obtained results indicate that HFO-1234yf is metabolized in rabbits by a CYP450
      mediated epoxidation at low rates and glutathione conjugation of the epoxide. The
      differences in urinary metabolite patterns between rats and rabbits seen with HFO
      1234yf are likely due to species-specific processing of glutathione S-conjugates.
      Rabbits also show a larger extent of biotransformation of HFO-1234yf.

PMID- 20045019
TI  - Overview: Harmful algal blooms and natural toxins in fresh and marine waters -
      Exposure, occurrence, detection, toxicity, control, management and policy.

PMID- 20045021
TI  - Changes in emotional behavior produced by orexin microinjections in the
      paraventricular nucleus of the thalamus.
AB  - The paraventricular nucleus of the midline thalamus (PVT) innervates areas of the
      extended amygdala known to play a key role in the expression of emotional
      behaviors. In this study, microinjections of orexins (hypocretins), which have
      excitatory actions on neurons in the PVT, in the midline thalamus were used to
      investigate if the PVT modulates the expression of emotional behavior in the open
      field. First, the approach-avoidance tendency (number and duration of visit to
      the center area) associated with novelty was examined in orexin treated rats
      before and after placing a novel object in the center of the open field. Second,
      the expression of ethological behaviors (rearing, locomotion, freezing, and
      grooming) in the open field was used to determine the effects of orexins on
      emotionality. Microinjections of orexin-A (OXA) or orexin-B (OXB) in the PVT
      decreased exploration of the center area and the novel object indicating that the
      center area and the object had more aversive properties in orexin treated rats.
      Both OXA and OXB microinjections in the PVT increased the expression of freezing
      and grooming behaviors which are indicative of a negative emotional state. The
      results indicate that microinjections of orexins in the PVT made the test
      situation more aversive and produced avoidance behaviors. This suggests that
      orexins may act at the PVT to modulate behaviors associated with a negative
      emotional state.

PMID- 20045020
TI  - A possible link between sensation-seeking status and positive subjective effects
      of oxycodone in healthy volunteers.
AB  - Sensation-seeking is a personality trait that is linked to use and abuse of
      drugs. Laboratory studies have established that high sensation seekers, as
      measured by different instruments, are more likely to report abuse liability
      related subjective effects from drugs such as nicotine, alcohol, and d
      amphetamine than low sensation seekers. One class of drugs that has not been
      studied to date in this fashion is opioids. Accordingly, a retrospective analysis
      encompassing five studies that examined oxycodone effects, including its abuse
      liability-related effects, was conducted in subjects categorized as high or low
      sensation seekers. In addition, because there appear to be sex differences in how
      males and females respond to opioids, this factor was taken into account in the
      analysis. Seventy one subjects who scored on the lower end (15 and 19 low
      sensation-seeking males and females, respectively) or the higher end (23 and 14
      high sensation-seeking males and females) of the Disinhibition subscale of the
      Sensation-Seeking Scale-Form V were studied for their responses to 0, 10, and
      20mg of oral oxycodone. Ratings of "pleasant bodily sensations" were
      significantly higher after oxycodone administration than placebo only in male and
      female high sensation seekers. Ratings of "take again," "drug liking,"
      "carefree," and "elated (very happy)" also tended to differentiate high from low
      sensation seekers although Group x Dose interactions were only marginally
      significant with the latter three ratings. Male and female low sensation seekers
      and female high sensation seekers reported dysphoric effects (e.g., ratings of
      nauseated) particularly after administration of the 20mg oxycodone dose. The
      results of this analysis provide suggestive evidence that high sensation seekers
      are more likely to experience greater positive subjective effects from oxycodone
      than low sensation seekers, but likelihood of experiencing negative effects is
      more complex (involving both sensation-seeking status and sex).

PMID- 20045022
TI  - Interactions between the effects of early isolation rearing and complex housing
      on adult locomotor activity and sensitivity to amphetamine in rats involve
      noradrenergic neurotransmission.
AB  - Increased sensitivity to the locomotor-activating effects of amphetamine in rats
      with a history of early-life social isolation is commonly attributed to
      alteration of the dopamine system. The locomotor response to amphetamine may also
      be due to effects on the noradrenergic system and particularly alpha-adrenergic
      receptors. The present study examined whether noradrenergic neurotransmission
      mediates the increased sensitivity to the locomotor effects of amphetamine
      resulting from early social isolation and whether this effect can be reversed by
      later-life social housing experience. Rats reared in complete social isolation
      (artificially reared, AR) exhibited higher levels of locomotor activity than
      maternally reared (MR) rats in response to amphetamine (0.25mg/kg). Increased
      sensitivity to the locomotor effects of amphetamine in AR rats was reduced by the
      alpha-adrenergic receptor antagonist prazosin (0.5mg/kg). Prazosin alone reduced
      activity in AR rats to the level of MR rats. Group housing in cages that were
      more complex than standard laboratory cages reduced activity in both AR and MR
      rats. Group housing did not decrease the sensitivity of AR rats to the locomotor
      effects of either amphetamine or prazosin. Differences in activity between rats
      in standard and complex housing conditions were not altered by drug treatments.
      These findings indicate that pre-weaning social experience alters the
      responsiveness of the noradrenergic system to drug challenges, whereas post
      weaning housing experience may not, even though ongoing activity is affected.
      Increased activity and sensitivity to amphetamine resulting from social isolation
      in early life may be mediated by changes in noradrenergic alpha-receptor mediated
      neurotransmission.

PMID- 20045023
TI  - The FARE: a new way to express FAlls Risk among older persons including physical
      activity as a measure of exposure.
AB  - BACKGROUND: Common expressions of falls risk do not include exposure to hazards.
      We compared two expressions: the commonly used population incidence (fallers per
      1000 person-years) and the FARE (FAlls Risk by Exposure): the number of fallers
      per 1000 physically active person-days. METHODS: Prospective follow-up study
      among community dwelling older persons (N=771) aged between 71 and 96 years in
      The Netherlands, 2005. Baseline data on age, gender, disabilities (vision,
      mobility), and number of days per week with minimally 30 min of physical activity
      were collected. Falls were registered monthly. Falls risk was expressed as the
      number of falls per 1000 person-years and as the FARE. A balance control
      difficulty score was based on the sumscore of 11 disability items. RESULTS:
      Increased difficulty controlling balance was linearly associated with reduced
      exposure to risky situations (Spearman correlation coefficient=-.56) and to an
      increased falls risk per 1000 person-years. In contrast, the FARE score increased
      exponentially, which is more indicative of the real risk people face, taking into
      account their activity restriction. CONCLUSIONS: The FARE is recommended for use
      in public health policy and research on falls prevention because it takes into
      account reduced physical activity of older persons who experience increased
      difficulty controlling their balance.

PMID- 20045024
TI  - Identification and functional characterization of a human sTRAIL homolog,
      CasTRAIL, in an invertebrate oyster Crassostrea ariakensis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is one of
      the tumor necrosis factor (TNF) superfamily members, participating in many
      biological processes including apoptosis and immune responses. In present study,
      a novel human soluble TRAIL (sTRAIL) homolog, CasTRAIL was identified from the
      oyster, Crassostrea ariakensis. CasTRAIL has a 99% and 98% similarity to human
      sTRAIL over the cDNA sequence and the amino acid sequence, respectively. It
      mostly distributes in tissues of the oyster defense system and was mainly
      localized at cell membrane, and has no cytotoxicity to normal hemocytes of
      oyster. The phosphorylation state of MAP kinases revealed that CasTRAIL induced a
      rapid increase in the phospho-ERK and phospho-p38 levels, which indicated that
      the MAPK pathway was involved in CasTRAIL-mediated signaling. In addition,
      CasTRAIL also showed an ability of anti-RLO infection which might be through the
      p38-MAPK activation pathway. Present studies provide an understanding and insight
      of the biological functions of CasTRAIL.

PMID- 20045025
TI  - Polymorphism of the superoxide dismutase gene family in the bay scallop
      (Argopecten irradians) and its association with resistance/susceptibility to
      Vibrio anguillarum.
AB  - The superoxide dismutases (SODs) are a family of enzymes that function as the
      first line of antioxidant defense against highly reactive superoxide radicals.
      The bay scallop Argopecten irradians contains three unique superoxide dismutases:
      Ai-icCuZnSOD, Ai-MnSOD and Ai-ecCuZnSOD, which were characterized in our previous
      studies. qRT-PCR was also performed to characterize the temporal expression of
      SODs in the hemocytes of bay scallops injected with the bacterium Vibrio
      anguillarum. To characterize the SOD family in A. irradians completely, we
      evaluated the polymorphism in the SOD genes and investigated the association of
      this polymorphism with resistance/susceptibility to V. anguillarum. Fifty-nine
      SNPs were identified in the promoter, exon and partial intron sequences of the
      three SOD genes. AiECSOD contained the most SNPs, as compared to AiCuZnSOD and
      AiMnSOD, and the majority of these were located in the promoter. Among them, the
      genotypes of -1739 T-C SNP in the AiCuZnSOD promoter and alleles of the -498 A-T
      and -267 G-A SNPs in the AiECSOD promoter showed a significant association with
      resistance/susceptibility to V. angullarum (P<0.05). The only non-synonymous SNP
      that was identified, E1-38 C-A in Ai-ecCuZnSOD, was a dimorphism caused by a C to
      A transition that resulted in a Thr to Lys substitution at position 13 in the
      signal peptide. The Thr allele was associated with increased susceptibility to V.
      anguillarum (P<0.05). To confirm the presumption, another independent challenge
      experiment was performed, in which the cumulative mortality of Ai-icCuZnSOD Q
      1739 genotype TT was significantly lower than TC (P<0.05). Ai-ecCuZnSOD Q-498
      genotype AA and AT were significantly lower than TT (P<0.05), Ai-ecCuZnSOD E1-3
      genotype AA was significantly higher than CA and CC (P<0.05). The results
      suggested that these three polymorphic loci could be potential gene markers for
      the future molecular selection of strains that are resistant to diseases caused
      by V. anguillarum.

PMID- 20045026
TI  - Zebrafish larvae are unable to mount a protective antiviral response against
      waterborne infection by spring viremia of carp virus.
AB  - Interferons (IFNs) and their receptors exist in all classes of vertebrates, where
      they represent early elements in innate and adaptive immunity. Both types I and
      II IFNs have been discovered in fish and type I IFN has recently been classified
      into two groups based on their primary protein sequences and biological
      activities. Thus, although groups I and II zebrafish IFN show powerful antiviral
      activities, only group I (IFNphi1) is able to protect the fish against bacterial
      infection. In addition, group II IFNs (IFNphi2 and IFNphi3) induce a rapid and
      transient expression of antiviral genes, while group I IFN exerts a slow but more
      powerful induction of several antiviral and pro-inflammatory genes. To gain
      further insight into the IFN system of fish, we have developed a waterborne
      infection model of zebrafish larvae with the spring viremia of carp virus (SVCV).
      Larvae were challenged 3 days post-fertilization by immersion, which considerably
      reduces the manipulation of fish and represents a more natural route of
      infection. Using this infection model, we unexpectedly found an inability on the
      part of zebrafish larvae to mount a protecting antiviral response to waterborne
      SVCV. Nevertheless, zebrafish larvae showed a functional antiviral system since
      ectopic expression of the cDNA of both groups I and II IFN was able to protect
      them against SVCV via the induction of IFN-stimulated genes (ISGs).
      Interestingly, group II IFNs also induced group I IFN, suggesting crosstalk
      between these two kinds of antiviral IFN. These results further confirm the
      antiviral activities of type I IFN in the zebrafish and provide the first viral
      infection model for zebrafish larvae using a natural route of infection. This
      model, in combination with the powerful gene overexpression and morpholino
      mediated knockdown techniques, will help to illuminate the IFN system of teleost
      fish.

PMID- 20045027
TI  - Epithelial induction of porcine suppressor of cytokine signaling 2 (SOCS2) gene
      expression in response to Entamoeba histolytica.
AB  - Suppressor of cytokine signaling (SOCS) proteins are key physiological regulators
      of both innate and adaptive immunity. These proteins belong to the three major
      classes of modulators of cytokines signaling. In the following article, we used
      porcine polarized intestinal cells to study early response to the protozoan,
      Entamoeba histolytica, and we identified by rapid amplification of cDNA ends
      (RACE) PCR porcine SOCS1, SOCS4, SOCS5 and SOCS6 encoding sequences. With more
      than 92% identity predicted porcine SOCS proteins are very similar to their human
      counterparts. Among SOCS transcripts, only SOCS2 mRNA was significantly induced
      in epithelial intestinal cells in response to the cytolytic activity of the
      parasite. The transcriptomic profile obtained after 3h of co-culture of polarized
      intestinal cells with E. histolytica was clearly oriented toward inflammation and
      the recruitment of neutrophils. These transcriptomic data have been normalized
      with accuracy by the utilisation of multiple validated reference genes. The
      analysis offers a first set of reference genes useful for future studies in
      porcine intestinal cells. Our data shed light on the understanding of the early
      response of polarized intestinal cells to E. histolytica and identified a
      potential involvement of SOCS2 in the parasite regulation of the host response.

PMID- 20045028
TI  - HIV-1 and HCV detection in dried blood spots by SYBR Green multiplex real-time RT
      PCR.
AB  - Dried blood spot (DBS) is a reliable method of blood collection used for the
      diagnosis of several human diseases. DBS is particularly useful for diagnosing
      children and for the screening of high-risk populations especially in countries
      where health facilities are not readily accessible. This report describes a
      qualitative SYBR Green-based real-time multiplex RT-PCR for the simultaneous
      detection of hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV
      1) genomes in DBS. Specific viral amplicons were identified in the same sample by
      their distinctive melting temperatures. The analysis of scalar concentrations of
      the reference samples indicated that this multiplex procedure detects at least
      2500 copies/ml of HCV and 400 copies/ml of HIV-1. HIV-1 and HCV viral loads in 20
      patients infected with HIV-1 and/or HCV and in 5 healthy blood donors were also
      tested, confirming the sensitivity and specificity of the assay. This method may
      represent a reliable alternative for the detection of HIV-1/HCV co-infection, in
      rapid and relatively inexpensive screening programmes.

PMID- 20045029
TI  - A dispensable Plasmodium locus for stable transgene expression.
AB  - The ribosomal small subunit locus has been used for transgene expression in the
      rodent malaria parasites, Plasmodium berghei and Plasmodium yoelii, but this
      strategy utilizes single crossover integration and is thus prone to reversion by
      plasmid excision. Targeting of the ribosomal subunit locus may also have a
      negative effect on oocyst development in the mosquito. In P. berghei, the p230
      paralog locus has been used for transgene expression. Here, we show that the P.
      yoelii S1 locus (sporozoite expressed gene 1) (PY05712) is dispensable and can be
      used for stable transgene expression throughout the parasite life cycle. P.
      yoelii s1(-) parasites show no defect in blood stage replication, oocyst
      formation, sporozoite production, or liver stage development when compared to P.
      yoelii wildtype parasites. Further, we show that a fluorescent transgene can be
      stably expressed from this site. This demonstrates that the S1 locus can be
      utilized for stable expression of heterologous genes in rodent malaria parasites.

PMID- 20045030
TI  - The pir multigene family of Plasmodium: antigenic variation and beyond.
AB  - Multigene families are present on the telomeric and sub-telomeric regions of most
      chromosomes of the malaria parasite, Plasmodium. The largest gene family
      identified so far is the Plasmodium interspersed repeat (pir) multigene gene
      family and is shared by Plasmodium vivax, and simian and rodent malaria species.
      Most pir genes share a similar structure across the different species; a short
      first exon, long second exon and a third exon encoding a trans-membrane domain,
      and some pir genes can be assigned to specific sub-families. Although pir genes
      can be differentially transcribed in different life cycle stages, suggesting
      different functions, there is no clear link between sub-family and transcription
      pattern. Some of the pir genes encode proteins expressed on or near the surface
      of infected erythrocytes, and therefore could be potential targets of the host's
      immune response, and involved in antigenic variation and immune evasion. Other
      functions such as signalling, trafficking and adhesion have been also postulated.
      The presence of pir in rodent models will allow the investigation of this gene
      family in vivo and thus their potential as vaccines or in other interventions in
      human P. vivax infections.

PMID- 20045031
TI  - Central ghrelin inhibits reflex swallowing elicited by activation of the superior
      laryngeal nerve in the rat.
AB  - The effect of ghrelin on rhythmic reflex swallowing was examined in urethane
      chloralose anesthetized rats. Swallowing was monitored by recording
      electromyographic activities of the suprahyoid muscle. Fourth ventricular
      administration of ghrelin decreased swallowing frequency during electrical
      stimulation of the central cut end of the superior laryngeal nerve (SLN
      stimulation). A significant decrease in swallowing frequency was observed after
      ghrelin administration at doses of 3, 10, 30 and 100 pmol. The administration of
      ghrelin with growth hormone secretagogue receptor antagonist ([D-Lys(3)] GHRP-6)
      did not change swallowing frequency during SLN stimulation. Neither mean blood
      pressure nor heart rate changed after the administration of 10 pmol ghrelin.
      Bilateral vagotomy did not disrupt the ghrelin response. These observations
      indicate that the ghrelin response does not depend on either cardiovascular or
      abdominal responses. Microinjection of ghrelin (0.3 pmol) into the vicinity of
      the solitary tract inhibited swallowing induced by SLN stimulation. Fourth
      ventricular administration of orexin-A (3 nmol) also inhibited reflex swallowing
      elicited by SLN stimulation. These results suggest that ghrelin and other
      orexigenic peptides inhibit reflex swallowing by modifying neural activities of
      the dorsal medulla where the swallowing center is housed.

PMID- 20045032
TI  - Biotechnological applications of microbial proteomes.
AB  - Advances in proteomic technologies have led to the creation of large-scale
      proteome databases that can be used to elucidate invaluable information on the
      dynamics of the metabolic, signaling and regulatory networks and to aid
      understanding of physiological changes. In particular, proteomics can have
      practical applications, for example, through the identification of proteins that
      may be potential targets for the biotechnology industry, and through the
      extension of our understanding of the physiological action of these proteins. In
      this review, we describe proteomic approaches for the discovery of targets that
      have potential biotechnological applications. These targets include promoters,
      chaperones, soluble fusion partners, anchoring motifs, and excretion fusion
      partners. In addition, we discuss the potential applications of proteomic
      techniques for the design of future bioprocesses and the optimization of existing
      ones. Successful applications of proteomic information have proven to have
      enormous value for both scientific and practical applications.

PMID- 20045033
TI  - SecretP: a new method for predicting mammalian secreted proteins.
AB  - In contrast to a large number of classically secreted proteins (CSPs) and non
      secreted proteins (NSPs), only a few proteins have been experimentally proved to
      enter non-classical secretory pathways. So it is difficult to identify non
      classically secreted proteins (NCSPs), and no methods are available for
      distinguishing the three types of proteins simultaneously. In order to solve this
      problem, a data mining has been taken firstly, and mammalian proteins exported
      via ER-Golgi-independent pathways are collected through extensive literature
      searches. In this paper, a support vector machine (SVM)-based ternary classifier
      named SecretP is proposed to predict mammalian secreted proteins by using pseudo
      amino acid composition (PseAA) and five additional features. When distinguishing
      the three types of proteins, SecretP yielded an accuracy of 88.79%. Evaluating
      the performance of our method by an independent test set of 92 human proteins, 76
      of them are correctly predicted as NCSPs. When performed on another public
      independent data set, the prediction result of SecretP is comparable to those of
      other existing computational methods. Therefore, SecretP can be a useful
      supplementary tool for future secretome studies. The web server SecretP and all
      supplementary tables listed in this paper are freely available at
      http://cic.scu.edu.cn/bioinformatics/secretp/index.htm.

PMID- 20045034
TI  - Expression of the spexin gene in the rat adrenal gland and evidences suggesting
      that spexin inhibits adrenocortical cell proliferation.
AB  - Spexin (SPX, also called NPQ) is a recently identified, highly conserved peptide
      which is processed and secreted. We analysed the SPX gene and its protein product
      in the rat adrenal gland to ascertain whether SPX is involved in the regulation
      of corticosteroid secretion of and growth of adrenocortical cells. In adult rat
      adrenal glands the highest levels of SPX mRNA were present in the glomerulosa
      (ZG) and fasciculate/reticularis (ZF/R) zones. High SPX gene expression levels
      were found in freshly isolated adult rat ZG and ZF/R cells. In cultured
      adrenocortical cells the levels of SPX mRNA were lower than in freshly isolated
      cells. SPX mRNA expression levels were found to be 2-3 times higher during days
      90-540 of postnatal development than found during days 2-45. Prolonged ACTH
      administration lowered and dexamethasone increased adrenal SPX mRNA levels in
      vivo. Adrenal enucleation produced a significant linear increase in SPX mRNA
      levels, with the highest value occurring at day 8 after surgery, with control
      values taken on day 30 after enucleation. Immunohistochemistry revealed SPX-like
      immunoreactivity in the entire cortex of the adult male rat and in enucleation
      induced regenerating cortex. A concentration of 10-6M SPX peptide stimulated
      basal aldosterone secretion by freshly isolated ZG. In prolonged exposure of
      adrenocortical cell primary cultures to SPX (10-6M) resulted in a small increase
      in corticosterone secretion and a notable decrease in BrdU incorporation. The
      results suggest the direct involvement of SPX in the regulation of adrenocortical
      cell proliferation; however, the mechanism of action remains unknown.

PMID- 20045035
TI  - Antioxidant enzymatically modified isoquercitrin suppresses the development of
      liver preneoplastic lesions in rats induced by beta-naphthoflavone.
AB  - To investigate the modifying effect of enzymatically modified isoquercitrin
      (EMIQ) on hepatocellular tumor promotion induced by beta-naphthoflavone (BNF)
      treatment, male rats were administered a single intraperitoneal injection of N
      diethylnitrosamine (DEN) and were fed a diet containing BNF (0.5%) for 6 weeks
      with or without EMIQ (0.2%) in the drinking water after DEN initiation. One week
      after the commencement of the administration of BNF, rats were subjected to a two
      thirds partial hepatectomy. The number and area of GST-P positive foci, the
      number of COX2-positive cells and the area of elastica-van Gieson (EVG)-positive
      connective tissue fibers promoted by BNF were significantly suppressed by the
      administration of the antioxidant EMIQ. Real-time RT-PCR analysis revealed that
      EMIQ treatment decreased mRNA expression levels of Gstm1, Serpine1, Cox2 and
      Nfkbia and increased mRNA expression levels of Yc2 compared with those in the DEN
      BNF group. These results suggest that co-administration of EMIQ suppresses the
      hepatocellular tumor-promoting activity of BNF in rats through the anti
      inflammatory effects of EMIQ and restores the cellular redox balance altered by
      BNF.

PMID- 20045036
TI  - Influence of the degree of dentine mineralization on pulp chamber temperature
      increase during resin-based composite (RBC) light-activation.
AB  - OBJECTIVES: To analyse the influence of the degree of dentine mineralization on
      the pulp chamber temperature increase during composite light-activation. METHODS:
      Dentine discs (2mm thick) obtained from recently extracted teeth or those with
      extensive dentine sclerosis were analysed by FT-IR spectrometry in order to
      choose the two discs with the greatest difference in the degree of
      mineralization. A model tooth was set up with the dentine discs between a molar
      with the pulp chamber exposed and a crown with a standardized class II cavity. A
      K-type thermocouple was introduced into the molar root until it came into contact
      with the dentine discs and the cavity was filled with P60 resin composite. The
      temperature rise was measured for 120s after light-activation began: Standard (S)
      600 mW/cm(2)/40s; Ramp (R) 0-->800 mW/cm(2)/10s+800 mW/cm(2)/10s; Boost (B) 85
      0mW/cm(2)/10s and LED (L) 1.300 mW/cm(2)/40s (n=10). The same protocol was
      repeated after grinding the dentine discs to 1.0 and 0.5mm thickness. RESULTS:
      The temperature increase was significantly higher in dentine with high degree of
      mineralization (p<0.05). With respect to the dentine thickness, the following
      result was found: 2mm<1mm<0.5mm (p<0.05). The light-activation mode also
      presented significant difference as follows: S>R=L>B (p<0.05). CONCLUSIONS: The
      higher the degree of dentine mineralization the greater the increase in pulp
      chamber temperature. The temperature increase was influenced by the light
      polymerization mode and dentine thickness.

PMID- 20045037
TI  - Riboregulators in kidney development and function.
AB  - The discovery of microRNAs has brought in another level of intricacy in gene
      regulation. These microRNAs are small non-coding RNAs that have dual ability to
      act as repressors or inducers of gene activity. MicroRNAs have been implicated in
      a wide spectrum of biological processes and their expressions have been found to
      be dysregulated in several diseases. Recently, microRNAs have emerged as a new
      area of interest in renal development and pathology. MicroRNA profilings have
      revealed a number of microRNAs that are specific to the kidney or restricted to
      certain regions of the organ suggesting possible exclusive roles therein.
      Recently, knockout studies have shown that these riboregulators are critical for
      normal renal growth and functional renal system. Individual microRNAs have also
      been identified in renal disease models including kidney cancers, diabetic
      nephropathy and polycystic kidney disease. Several mechanisms of modulating
      microRNA activity have also been introduced in recent years. Further progress in
      the understanding of microRNA activity, identification of microRNA signatures in
      different states as well as advancement of microRNA manipulation techniques will
      be valuable for kidney research.

PMID- 20045038
TI  - Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR.
AB  - Control of stem cell state and differentiation of neural stem/progenitor cells is
      essential for proper development of the nervous system. EGF and FGF2 play
      important roles in the control of neural stem/progenitor cells, but the
      underlying mechanism still remains unclear. Here we show, using in vitro primary
      cultures of mouse neural stem/progenitor cells, that both PI3K and mTOR are
      activated by EGF/FGF2 but that inhibiting the activation of either PI3K or mTOR
      alone results in only reduced proliferation of neural stem/progenitor cells
      without affecting their stem cell state, namely, the capacity to self-renew.
      However, significantly, concurrent inhibition of PI3K and mTOR promoted exit from
      the stem cell state together with astrocytic differentiation of neural
      stem/progenitor cells. These findings suggest that PI3K and mTOR are involved in
      the EGF/FGF2-mediated maintenance of neural stem/progenitor cells and that they
      may act in parallel and independent pathways, complementing and backing up each
      other to maintain the stem cell state.

PMID- 20045039
TI  - Palmitone prevents pentylenetetrazole-caused neuronal damage in the CA3
      hippocampal region of prepubertal rats.
AB  - Palmitone is a secondary metabolite of polyketide origin extracted from leaves of
      Annona diversifolia Saff. (Annonaceae). We found that palmitone possesses
      anticonvulsant properties against penicillin-, 4-AP-, and pentylenetetrazole
      (PTZ)-caused seizure in adult animals. Some convulsants as PTZ cause neuronal
      damage in different brain regions such as the CA3 hippocampal region. Our
      objective was to evaluate if palmitone protects against PTZ-caused seizures and
      hippocampal neuronal damage in prepubertal rats. We used 32 prepubertal Wistar
      rats (30-35 days old) divided into four groups of 8 animals; group I was the
      control group, group II received a single PTZ dose of 50mg/kg ip, group III
      received a single palmitone dose of 50mg/kg ip, and group IV received a palmitone
      dose of 50mg/kg ip plus a PTZ dose of 50mg/kg ip. Ten days after administration,
      the animals were killed using pentobarbital anesthesia (35 mg/kg). The brains
      were removed and were embedded in paraffin. Coronal cuts of 7 microm were
      obtained from -2.8 to -3.3 from Bregma. Each section was stained with cresyl
      violet-eosin. We evaluated the number of normal and abnormal neurons in the CA3
      hippocampal region in a 10,000 microm(2) section. It was observed that palmitone
      did not prevent the PTZ-caused seizure but palmitone prevents the PTZ-caused
      neuronal damage in the CA3 hippocampal region.

PMID- 20045040
TI  - Microneurography: an opportunity for translational drug development in
      neuropathic pain.

PMID- 20045041
TI  - Characterization of organogel as a novel oral controlled release formulation for
      lipophilic compounds.
AB  - A low molecular mass gelator can form soft solids in a variety of organic liquids
      and vegetable oils. These soft solids are generally called organogels. In this
      study, we prepared organogel using 12-hydroxystearic acid (12-HSA) as a gelator
      for soybean oil and investigated its characteristics as a controlled release
      formulation for lipophilic compounds. The release rate of ibuprofen, a model
      lipophilic compound, from organogel decreased with the increase of 12-HSA
      concentration in the formulation; however, the difference in the concentration of
      12-HSA in the formulation did not affect the diffusivity of ibuprofen in the
      organogel. The erosion constant of organogel in the intestinal tract was examined
      by using simulated gastric fluid and intestinal fluid. Regardless of 12-HSA
      concentration in the formulation, organogel is very stable in the simulated
      gastric fluid. On the other hand, the erosion constant of organogel in the
      simulated intestinal fluid increased with the decreasing concentration of 12-HSA.
      Therefore, it is speculated that the difference in the release rate of ibuprofen
      among organogels with various concentrations of 12-HSA was mainly caused by the
      difference in the erosion rate. To characterize the organogel effect in vivo,
      ibuprofen was orally administered to rats in an aqueous suspension or organogel.
      Ibuprofen concentration in plasma rapidly increased after administration with an
      aqueous suspension, whereas organogel suppressed the rapid absorption. In
      conclusion, organogel is clearly useful as an oral controlled release formulation
      for lipophilic compounds.

PMID- 20045042
TI  - beta-Cyclodextrins influence on E-3,5,4'-trimethoxystilbene absorption across
      biological membrane model: a differential scanning calorimetry evidence.
AB  - E-3,5,4'-trimethoxystilbene (TMS) is a naturally occurring analog of resveratrol.
      The anti-neoplastic, antiallergic and anti-angiogenic activities of TMS have been
      recently reported. From the viewpoint of metabolism, TMS may be more favourable
      than resveratrol because all of its hydroxyl groups, which are subjected to
      extensive glucuronide or sulphate conjugation in the metabolic pathways of
      resveratrol, are protected by methylation. Moreover, methylation increases
      lipophilicity and may enhance cell membrane permeability, but it decreases its
      solubility in aqueous media. A way to increase TMS solubility can be represented
      by complexation with beta-cyclodextrins. In the present paper, the differential
      scanning calorimetry technique has been used to study the interaction of TMS with
      a biomembrane model constituted by dimyristoylphosphatidylcholine multilamellar
      vesicles. Furthermore, kinetic experiments have been carried out to follow the
      uptake of TMS by biomembranes in the presence of beta-cyclodextrins to gain
      information on the effect of beta-cyclodextrins on the uptake process. Our
      results indicate that opportune concentrations of beta-cyclodextrins greatly
      improve the uptake of TMS by biomembrane models.

PMID- 20045043
TI  - Freeze-dried, mucoadhesive system for vaginal delivery of the HIV microbicide,
      dapivirine: optimisation by an artificial neural network.
AB  - Dapivirine mucoadhesive gels and freeze-dried tablets were prepared using a 3x3x2
      factorial design. An artificial neural network (ANN) with multi-layer perception
      was used to investigate the effect of hydroxypropyl-methylcellulose (HPMC):
      polyvinylpyrrolidone (PVP) ratio (X1), mucoadhesive concentration (X2) and
      delivery system (gel or freeze-dried mucoadhesive tablet, X3) on response
      variables; cumulative release of dapivirine at 24h (Q(24)), mucoadhesive force
      (F(max)) and zero-rate viscosity. Optimisation was performed by minimising the
      error between the experimental and predicted values of responses by ANN. The
      method was validated using check point analysis by preparing six formulations of
      gels and their corresponding freeze-dried tablets randomly selected from within
      the design space of contour plots. Experimental and predicted values of response
      variables were not significantly different (p>0.05, two-sided paired t-test). For
      gels, Q(24) values were higher than their corresponding freeze-dried tablets.
      F(max) values for freeze-dried tablets were significantly different (2-4 times
      greater, p>0.05, two-sided paired t-test) compared to equivalent gels. Freeze
      dried tablets having lower values for X1 and higher values for X2 components
      offered the best compromise between effective dapivirine release, mucoadhesion
      and viscosity such that increased vaginal residence time was likely to be
      achieved.

PMID- 20045044
TI  - Iontophoretic transport of charged macromolecules across human sclera.
AB  - The mechanisms of transscleral iontophoresis have been investigated previously
      with small molecules in rabbit sclera. The objective of the present study was to
      examine transscleral iontophoretic transport of charged macromolecules across
      excised human sclera. Passive and 2mA iontophoretic transport experiments were
      conducted in side-by-side diffusion cells with human sclera. The effects of
      iontophoresis upon transscleral transport of model permeants bovine serum albumin
      (BSA) and polystyrene sulfonic acid (PSS) as well as a model drug bevacizumab
      (BEV) were determined. Passive and iontophoretic transport experiments of
      tetraethylammonium (TEA) and salicylic acid (SA) and passive transport
      experiments of the macromolecules served as the controls. The results of
      iontophoresis enhanced transport of TEA and SA across human sclera were
      consistent with those in a previous rabbit sclera study. For the iontophoretic
      transport of macromolecules BSA and BEV, higher iontophoretic fluxes were
      observed in anodal iontophoresis as compared to passive and cathodal
      iontophoresis. This suggests the importance of electroosmosis. For the
      polyelectrolyte PSS, higher iontophoretic flux was observed in cathodal
      iontophoresis compared to anodal iontophoresis. Both electroosmosis and
      electrophoresis affected iontophoretic fluxes of the macromolecules; the relative
      contributions of electroosmosis and electrophoresis were a function of molecular
      size and charge of the macromolecules.

PMID- 20045045
TI  - Erythritol: crystal growth from the melt.
AB  - The structural changes occurring on erythritol as it is cooled from the melt to
      low temperature, and then heated up to the melting point have been investigated
      by differential scanning calorimetry (DSC), polarized light thermal microscopy
      (PLTM), X-ray powder diffraction (PXRD) and Fourier transform infrared
      spectroscopy (FTIR). By DSC, it was possible to set up the conditions to obtain
      an amorphous solid, a crystalline solid, or a mixture of both materials in
      different proportions. Two crystalline forms have been identified: a stable and a
      metastable one with melting points of 117 and 104 degrees C, respectively. The
      fusion curve decomposition of the stable form revealed the existence of three
      conformational structures. The main paths of the crystallization from the melt
      were followed by PLTM. The texture and colour changes allowed the
      characterization of the different phases and transitions in which they are
      involved on cooling as well as on heating processes. The type of crystallization
      front and its velocity were also followed by microscopic observation. These
      observations, together with the data provided by PXRD, allowed elucidating the
      transition of the metastable form into the stable one. The structural changes
      occurring upon the cooling and subsequent heating processes, namely those arising
      from intermolecular hydrogen bonds, were also accompanied by infrared
      spectroscopy. Particular attention was given to the spectral changes occurring in
      the OH stretching region.

PMID- 20045046
TI  - Effect of vestibular labyrinth destruction on endocochlear potential and
      potassium concentration of the cochlea.
AB  - Partial labyrinthectomy can result in maintenance of hearing under certain
      circumstances, and the mechanism of the hearing impairment caused by
      labyrinthectomy is unclear. We hypothesized that disruption of the membranous
      labyrinth results in electrical leakage and electrolyte imbalance. This study
      investigated the change in cochlear function by measurement of endocochlear
      potential (EP) and potassium concentration ([K(+)]) caused by vestibular
      labyrinth destruction in the acute phase. Hartley guinea pigs underwent lateral
      semicircular canal (LSCC) transection with suctioning of the perilymph,
      ampullectomy, or destruction of the LSCC, superior SCC, and lateral part of the
      vestibule. The EP and [K(+)] were monitored using double-barreled ion-selective
      microelectrodes in the second turn of cochlea. The EP showed little to mild
      change after LSCC transectioning or ampullectomy, but declined variously and
      drastically after vestibulotomy. The EP did not recover but [K(+)] partially
      recovered after vestibulotomy. Disturbance of the mechanism of cochlear function
      caused by vestibular labyrinth destruction may involve reduction in the [K(+)]
      concentration in the endolymph.

PMID- 20045047
TI  - Changes in testicular morphology and steroidogenesis in adult rats exposed to
      Atrazine.
AB  - Atrazine is an herbicide considered as a potent endocrine disruptor, causing
      adverse effects on both gender of mammalian and non-mammalian species. Despite
      the known adverse effects of Atrazine, little is known about its action on male
      genital system, especially in adults. We evaluated the effects of Atrazine (50
      mg/kg, 200 mg/kg and 300 mg/kg) in the 3beta-hydroxysteroid dehydrogenase (3beta
      HSD) expression, plasmatic and testicular estrogen and testosterone levels,
      androgen receptor expression and morphological changes in adult rat testes.
      Atrazine at doses higher than 50 mg/kg resulted in decreased body weight,
      increased adrenal weight and transient increase in testis weight, followed by
      testis atrophy. A reduction in testosterone but increase in estradiol levels was
      observed. We showed for the first time that testicular 3beta-HSD protein was
      decreased, whereas in the adrenal it was unchanged. The results suggest that
      3beta-HSD inhibition may represent an alternative mechanism through which
      Atrazine affects the testicular androgenesis, leading to changes in
      spermatogenesis.

PMID- 20045048
TI  - Reproductive health effects of aflatoxins: a review of the literature.
AB  - CONTEXT: Although it is known that aflatoxins have many adverse health effects,
      there is no systematic summary of how it affects the reproductive system or its
      reproductive health effects. OBJECTIVE: Summarize evidence on the reproductive
      health effects of aflatoxins. RESULTS: The search yielded 121 potential studies,
      of which 25 were retained. One study found a higher concentration of aflatoxins
      in the semen of infertile men (40% of cases compared to 8% of controls). Six
      studies found significant associations or correlations between low birth weight
      and aflatoxins while one study did not find any correlation. One study found
      maternal serum aflatoxin to be a risk factor for jaundice in infants (OR, 2.68;
      CI, 1.18-6.10). Overall, maternal breast milk in developing countries had higher
      rates of aflatoxin contamination than in high income countries. CONCLUSIONS:
      Stakeholders in developing countries need to take steps to reduce exposure of
      vulnerable populations to the toxic effects of aflatoxins.

PMID- 20045049
TI  - Moderate developmental undernutrition: Impact on growth and cognitive function in
      youth and old age.
AB  - Low weight at birth is a common adverse developmental effect reported in human
      populations and animal toxicity studies. Epidemiological evidence links low birth
      weight to a syndrome of metabolic changes that increase later risk for obesity,
      type 2 diabetes, hypertension, and cardiovascular disease. The present study used
      a four-treatment cross-over experimental design to evaluate the selective impact
      of early nutritional deficiency on metabolism and brain function across the
      lifespan of male Sprague Dawley rats. Undernutrition was induced prenatally by
      restricting maternal food intake to 50% of ad lib from GD3 to birth. Postnatal
      undernutrition was induced by fostering pups at birth to naive dams in large
      (n=16) litters as opposed to small (n=8) control litters. Body weights were
      monitored in the early neonatal period, in early adulthood beginning at 5months
      and through to senescence at 21months of age. In contrast to recent reports, no
      increase in the prevalence of obesity was seen in animals born to food restricted
      dams and reared under ad lib feeding conditions. Behavioral tests of locomotion,
      learning and memory were performed in young, middle-aged, and aged animals. No
      effects of pre or postnatal nutritional history were detected. Age-dependent
      reductions in locomotor activity were detected, as well as deficits in spatial
      learning as measured in the Morris water maze and in context fear conditioning.
      These findings indicate that moderate fetal undernutrition followed by neonatal
      adequate nutrition does not appear to lead to obesity or neurological dysfunction
      in young adulthood or old age.

PMID- 20045050
TI  - Hepcidin induction limits mobilisation of splenic iron in a mouse model of
      secondary iron overload.
AB  - Venesection has been proposed as a treatment for hepatic iron overload in a
      number of chronic liver disorders that are not primarily linked to mutations in
      iron metabolism genes. Our aim was to analyse the impact of venesection on iron
      mobilisation in a mouse model of secondary iron overload. C57Bl/6 mice were given
      oral iron supplementation with or without phlebotomy between day 0 (D0) and D22,
      and the results were compared to controls without iron overload. We studied serum
      and tissue iron parameters, mRNA levels of hepcidin1, ferroportin, and
      transferrin receptor 1, and protein levels of ferroportin in the liver and
      spleen. On D0, animals with iron overload displayed elevations in iron parameters
      and hepatic hepcidin1 mRNA. By D22, in the absence of phlebotomies, splenic iron
      had increased, but transferrin saturation had decreased. This was associated with
      high hepatic hepcidin1 mRNA, suggesting that iron bioavailability decreased due
      to splenic iron sequestration through ferroportin protein downregulation. After
      22days with phlebotomy treatments, control mice displayed splenic iron
      mobilisation that compensated for the iron lost due to phlebotomy. In contrast,
      phlebotomy treatments in mice with iron overload caused anaemia due to inadequate
      iron mobilisation. In conclusion, our model of secondary iron overload led to
      decreased plasma iron associated with an increase in hepcidin expression and
      subsequent restriction of iron export from the spleen. Our data support the
      importance of managing hepcidin levels before starting venesection therapy in
      patients with secondary iron overload that are eligible for phlebotomy.

PMID- 20045051
TI  - Solid-state stability studies of cholecystokinin (CCK-4) peptide under
      nonisothermal conditions using thermal analysis, chromatography and mass
      spectrometry.
AB  - The solid-state stability of cholecystokinin (CCK-4) peptide under nonisothermal
      conditions was studied by differential scanning calorimetry (DSC), chromatography
      and mass spectrometry, identifying and schematizing the degradation products. To
      model the degradation mechanism of the peptide using the combined Kissinger and
      direct-differential methods, the observed degradation process was characterized
      by decomposition temperature (T(m)), reacted fraction (alpha(m)), activation
      energy (E(a)), and pre-exponential factor (A). Results obtained by the two
      calculation methods were similar. The cleavage reaction on both N- and C-terminal
      sides of aspartic acid was the principal degradation pathway, although the
      reaction can occur consecutively and/or in parallel. Therefore to determine the
      relative importance of the different degradation pathways, a system of
      differential equations relevant to each degradation reaction was analysed using
      the R((R)) statistical program. The results obtained show that the consecutive
      reaction was the less plausible, whereas a slightly better fit was obtained for
      the reaction with both processes than for the in-parallel reaction. In this
      situation, the F-test was applied to discriminate between the models, indicating
      that the simpler model is the most probable. In conclusion, the results
      demonstrate for the first time that, in solid-state, n-1 cleavage occurs in
      parallel to n+1 cleavage at aspartic acid residues and not consecutively.

PMID- 20045052
TI  - 11beta-Hydroxysteroid dehydrogenase type 1 is an important regulator at the
      interface of obesity and inflammation.
AB  - Systemic glucocorticoid excess, as exemplified by the Cushing syndrome, leads to
      obesity and all further symptoms of the metabolic syndrome. The current obesity
      epidemic, however, is not characterized by increased plasma cortisol
      concentrations, but instead comes along with chronic low-grade inflammation in
      adipose tissue and concomitant increased levels of 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1, gene HSD11B1), a parameter known to cause
      obesity in a mouse model. 11beta-HSD1 represents an intracellular amplifier of
      active glucocorticoid, thus enhances the associated effects on the inflammatory
      response as well as on nutrient and energy metabolism, and may therefore cause
      and exacerbate obesity by local increase of glucocorticoid concentrations.
      Obtained by extensive literature and database searching, the present review
      includes comprehensive lists of primary glucocorticoid-sensitive genes and gene
      products as well as of the thus far known regulators of HSD11B1 expression with
      implication in inflammation and metabolic disease. Collectively, the data clearly
      show that, in addition to amplifying active glucocorticoid and thus profoundly
      modulating inflammation and nutrient metabolism, 11beta-HSD1 is subject to tight
      control of multiple additional immunomodulatory and metabolic regulators. Hence,
      11beta-HSD1 acts at the interface of inflammation and obesity and represents an
      efficient integrator and effector of local inflammatory and metabolic state.

PMID- 20045053
TI  - Alterations of cortical and hippocampal EEG activity in MeCP2-deficient mice.
AB  - Rett syndrome is a pediatric neurological condition caused by mutations of the
      gene encoding the transcriptional regulator MECP2. In this study, we examined
      cortical and hippocampal electroencephalographic (EEG) activity in male and
      female MeCP2-deficient mice at symptomatic stages during different behavioral
      states. During acute sleep, MeCP2-deficient mice displayed normal delta-like
      activity in cortex and sharp-wave activity in hippocampus. However, when the mice
      were awake but immobile, abnormal spontaneous, rhythmic EEG discharges of 6-9 Hz
      were readily detected in the somatosensory cortex. During exploratory activity,
      MeCP2-deficient mice displayed clear theta rhythm activity in hippocampus, but
      its peak frequency was significantly attenuated compared to wild type.
      Collectively, these findings indicate that a deficiency in MeCP2 function in mice
      leads to alterations in EEG activity with similarities to what has been observed
      clinically in Rett syndrome patients.

PMID- 20045054
TI  - Modulation of astrocyte glutamate transporters decreases seizures in a mouse
      model of Tuberous Sclerosis Complex.
AB  - Astrocyte dysfunction may contribute to epileptogenesis and other neurological
      deficits in Tuberous Sclerosis Complex (TSC). In particular, decreased expression
      and function of astrocyte glutamate transporters have been implicated in causing
      elevated extracellular glutamate levels, neuronal death, and epilepsy in a mouse
      model of TSC (Tsc1(GFAP)CKO mice), involving inactivation of the Tsc1 gene
      primarily in astrocytes. Here, we tested whether pharmacological induction of
      astrocyte glutamate transporter expression can prevent the neurological phenotype
      of Tsc1(GFAP)CKO mice. Early treatment with ceftriaxone prior to the onset of
      epilepsy increased expression of astrocyte glutamate transporters, decreased
      extracellular glutamate levels, neuronal death, and seizure frequency, and
      improved survival in Tsc1(GFAP)CKO mice. In contrast, late treatment with
      ceftriaxone after onset of epilepsy increased glutamate transporter expression,
      but had no effect on seizures. These results indicate that astrocyte glutamate
      transporters contribute to epileptogenesis in Tsc1(GFAP)CKO mice and suggest
      novel therapeutic strategies for epilepsy in TSC directed at astrocytes.

PMID- 20045056
TI  - Antipsychotic-like effects of the N-methyl-D-aspartate receptor modulator
      neboglamine: an immunohistochemical and behavioural study in the rat.
AB  - Neboglamine is a functional modulator of the glycine site on the N-methyl-d
      aspartate (NMDA) receptor. Dysfunction of this receptor has been associated with
      negative and cognitive symptoms in schizophrenia. Thus, we tested the hypothesis
      that neboglamine behaves as a potential antipsychotic. We compared the effects of
      neboglamine, D-serine, clozapine, and haloperidol on the expression of Fos-like
      immunoreactivity (FLI), a marker of neuronal activation, in rat forebrain. We
      also studied the effects of these agents on phencyclidine (PCP)-induced behaviour
      in rats, a model predictive of potential antipsychotic activity. Neboglamine,
      like haloperidol and clozapine, significantly increased the number of FLI
      positive cells in the prefrontal cortex, nucleus accumbens, and lateral septal
      nucleus (3.2-, 4.8-, and 4.5-fold over control, respectively). Haloperidol
      dramatically increased FLI (390-fold over control) in the dorsolateral striatum,
      a brain region in which neboglamine and clozapine had no effect. The pattern of
      FLI induced by neboglamine closely matched that of d-serine, an endogenous
      agonist at the glycine site of NMDA receptors. Consistent with this finding,
      neboglamine restored NMDA-mediated neurotransmitter release in frontal cortex
      punches exposed to the NMDA antagonist PCP. In the behavioural model, all test
      compounds significantly inhibited PCP-induced hyperlocomotion. Unlike haloperidol
      and clozapine, neither neboglamine nor D-serine affected the basal levels of
      locomotor activity. Moreover, oral neboglamine dose-dependently inhibited both
      the hyperlocomotion and the frequency of rearing behaviour induced by PCP. These
      results, while confirming that the NMDA glycine site is a feasible target for
      activating the frontostriatal system, support the clinical evaluation of
      neboglamine as a treatment for schizophrenia.

PMID- 20045058
TI  - First molecular cloning of a molluscan caspase from variously colored abalone
      (Haliotis diversicolor) and gene expression analysis with bacterial challenge.
AB  - Mammal caspases have been demonstrated to possess important functions in
      apoptosis and immune signaling, but there is less knowledge available on abalone
      caspases. In the present study, a molluscan caspase gene, abCaspase, was cloned
      for the first time from the variously colored abalone (Haliotis diversicolor) and
      its full-length cDNA sequence was 2427 bp, with a 1008 bp of open reading frame
      encoding a protein of 336 aa. The molecular mass of the deduced protein was
      approximately 36.97 kDa with an estimated pI of 5.28. The predicted amino acid
      sequence of abCaspase contained two domains of p20 and p10 which were conserved
      in the caspase family, including the cysteine active site pentapeptide "QSCRG"
      and the histidine active site signature "HTVYDCVVVIFLTHG". Homology analysis
      showed that abCaspase shared high similarity with apoptotic caspases and it was
      grouped together with vertebrate caspase-8s and caspase-10s using phylogenetic
      analysis, suggesting that abCaspase belonged to a typical apoptotic caspase and
      might possess the characteristic of human caspase-8 and -10. The mRNA transcripts
      of abCaspase were widely distributed in various tissues of H. diversicolor.
      Expression of the abCaspase gene was significantly induced in the tissues tested,
      especially in the hemocytes, gill and mantle with bacterial challenge. This study
      suggested that abCaspase may be an initiator caspase associated with the
      induction of apoptosis which is potentially involved in the immune defense of H.
      diversicolor.

PMID- 20045057
TI  - Purification of transmembrane proteins from Saccharomyces cerevisiae for X-ray
      crystallography.
AB  - To enhance the quantity and quality of eukaryotic transmembrane proteins (TMPs)
      available for structure determination by X-ray crystallography, we have optimized
      protocols for purification of TMPs expressed in the yeast Saccharomyces
      cerevisiae. We focused on a set of the highest-expressing endogenous yeast TMPs
      for which there are established biochemical assays. Genes encoding the target
      TMPs are transferred via ligation-independent cloning to a series of vectors that
      allow expression of reading frames fused to C-terminal His10 and ZZ (IgG-binding)
      domains that are separated from the reading frame by a cleavage site for
      rhinovirus 3C protease. Several TMP targets expressed from these vectors have
      been purified via affinity chromatography and gel filtration chromatography at
      levels and purities sufficient for ongoing crystallization trials. Initial
      purifications were based on expression of the genes under control of a galactose
      inducible promoter, but higher cell densities and improved expression have been
      obtained through use of the yeast ADH2 promoter. Wide variations have been
      observed in the behavior of different TMP targets during purification; some can
      be readily purified, while others do not bind efficiently to affinity matrices,
      are not efficiently cleaved from the matrices, or remain tightly associated with
      the matrices even after cleavage of the affinity tags. The size, oligomeric
      state, and composition of purified protein-detergent complexes purified under
      different conditions were analyzed using a colorimetric assay of detergent
      concentrations and by analytical size-exclusion chromatography using static light
      scattering, refractive index, and UV absorption detection to monitor the elution
      profiles. Effective procedures were developed for obtaining high concentrations
      of purified TMPs without excessively concentrating detergents.

PMID- 20045059
TI  - AiCTL-6, a novel C-type lectin from bay scallop Argopecten irradians with a long
      C-type lectin-like domain.
AB  - C-type lectins are a superfamily of carbohydrate-recognition proteins which play
      crucial roles in the innate immunity. In this study, a novel C-type lectin gene
      from scallop Argopecten irradians (designated as AiCTL-6) was cloned by rapid
      amplification of cDNA ends (RACE) approach based on expression sequence tag (EST)
      analysis. The full-length cDNA of AiCTL-6 was 1080 bp. The open reading frame
      encoded a polypeptide of 307 amino acids, including a signal sequence and a C
      type lectin-like domain (CTLD) of 150 amino acid residues longer than any usual
      CTLD. It contained six conserved cysteine residues involved in the formation of
      three internal disulfide bridges and an EPD (Glu(269)-Pro(270)-Asp(271)) motif at
      the Ca(2+)-binding site 2. The deduced amino acid sequence of AiCTL-6 showed high
      similarity to members of C-type lectin superfamily. By fluorescent quantitative
      real-time PCR, AiCTL-6 mRNA was found mainly in hepatopancreas and gill, and
      marginally expressed in other tissues. After the scallops were challenged by
      Listonella anguillarum for 6 h, the mRNA expression of AiCTL-6 was up-regulated
      significantly to 7.2-fold compared to the blank group. While at 9 h post
      Micrococcus luteus challenge, its expression level was 60.1 times higher than
      that of the blank group. The functional activity of AiCTL-6 was investigated by
      recombination and expression of the cDNA fragment encoding its mature peptide in
      Escherichia coli Rosetta gami (DE3). The recombinant AiCTL-6 could agglutinate
      Gram-negative bacteria E. coli TOP10F', Gram-positive bacteria M. luteus and
      Staphylococcus aureus. These results collectively suggested that AiCTL-6, as a
      novel member of C-type lectin family, contributed to the host defense mechanisms
      against invading microorganism in A. irradians.

PMID- 20045060
TI  - Cloning and characterization of three novel WSSV recognizing lectins from shrimp
      Marsupenaeus japonicus.
AB  - C-type lectins (CTLs) acting as pattern recognition receptors play essential
      roles in shrimp innate immune responses. Using WSSV envelope proteins (VP26,
      VP28, and VP281) to screen a phage display library of Marsupenaeus japonicus,
      three lectins (termed as MjLecA, MjLecB, and MjLecC) were found to interact with
      WSSV. Sequence analysis revealed that these MjLecs shared low similarities with
      each other. Phylogenetic analysis indicated MjLecA and MjLecB are likely to
      belong to the same lectin sub-family, while MjLecC belongs to another sub-family.
      These MjLecs showed broad, unique carbohydrate binding spectra. Also, the three
      MjLecs could interact with several envelope proteins of WSSV and could recognize
      a wide range of microorganisms. Moreover, binding of MjLecA or MjLecB to WSSV
      reduced the viral infection rate in vitro. These results suggest that various
      kinds of CTLs with structural and functional diversities may constitute a
      recognizing network against invading pathogens such as bacteria and virus, and
      play essential roles in the defence system of shrimp.

PMID- 20045061
TI  - Immune responses and expression profiles of some immune-related genes in Indian
      major carp, Labeo rohita to Edwardsiella tarda infection.
AB  - Edwardsiella tarda is an important Gram-negative bacterium that causes systemic
      infections in a wide range of hosts including fish. The pathogenic mechanisms in
      this disease are still poorly understood in fish. Indian major carp, Labeo rohita
      were intraperitoneally challenged with a pathogenic isolate of E. tarda to
      measure sequential changes in immunity level. A significant decrease in the
      superoxide production, myeloperoxidase, alternative complement activity, total
      protein levels and antiprotease activity of serum was marked in the infected
      fish. However, the serum lysozyme activity and haemagglutination titre were
      raised in the infected fish. Similarly, a significant rise in specific antibody
      titre was noticed on and after 10 days post-challenge. This study also elucidates
      the changes in the relative expression of some immune-related genes viz.,
      interleukin 1-beta (IL-1beta), inducible nitric oxide synthase (iNOS), complement
      component C3, beta(2)-microglobulin, CXCa, tumor necrosis factor-alpha
      (TNFalpha), and C-type and G-type lysozymes during the infection. Significant up
      regulation of IL-1beta, iNOS, C3, CXCa and expression of both types of lysozyme
      genes was noticed at 6-12 h post-challenge (h.p.c.) whereas down-regulation of
      beta(2)-microglobulin and TNFalpha genes was observed after 48 h p.c. The results
      obtained here strengthen the understanding on molecular pathogenesis of
      edwardsiellosis in L. rohita.

PMID- 20045062
TI  - Concurrent injection of a rhabdovirus-specific DNA vaccine with a polyvalent, oil
      adjuvanted vaccine delays the specific anti-viral immune response in Atlantic
      salmon, Salmo salar L.
AB  - Vaccines are commonly used in salmonid aquaculture as a method of disease
      prevention. Although there is a substantial amount of published research
      regarding the immunological and physiological effects following the injection of
      different polyvalent vaccines and DNA vaccines, there are no published reports
      examining the physiological and immunological effects of concurrent vaccine
      injection, which is the situation encountered in aquaculture. Using key
      immunological parameters such as lysozyme activity and specific antibody titres
      we examined the short-term activation of the immune response of cultured Atlantic
      salmon (Salmo salar L.) following concurrent injection with a traditional,
      polyvalent, oil-adjuvanted vaccine (AV) and an IHNV-specific DNA vaccine (DV).
      Our results indicate that different aspects of the innate and adaptive immune
      responses are influenced in either a positive or negative manner. While
      concurrent vaccine injection elicited an increase in lysozyme activity, changes
      in antibody titre (Ab) were antigen specific. The production of anti-Aeromonas
      salmonicida Abs was significantly greater in the combined vaccine group at 296
      degree days post-vaccine injection (dd pvi), while the production of anti
      Listonella anguillarum Abs was significantly greater at 106 dd pvi in the
      combined vaccine group. Of even greater interest was the apparent delay in
      production of IHNV-specific neutralizing antibodies (NAb) when the DV was
      injected concurrently with the polyvalent AV. The results indicated that
      concurrent injection of a polyvalent oil-AV and a DV can be beneficial to the
      production of antibodies; however, the specific anti-viral response may be
      delayed.

PMID- 20045055
TI  - Enabling individualized therapy through nanotechnology.
AB  - Individualized medicine is the healthcare strategy that rebukes the idiomatic
      dogma of 'losing sight of the forest for the trees'. We are entering a new era of
      healthcare where it is no longer acceptable to develop and market a drug that is
      effective for only 80% of the patient population. The emergence of "-omic"
      technologies (e.g. genomics, transcriptomics, proteomics, metabolomics) and
      advances in systems biology are magnifying the deficiencies of standardized
      therapy, which often provide little treatment latitude for accommodating patient
      physiologic idiosyncrasies. A personalized approach to medicine is not a novel
      concept. Ever since the scientific community began unraveling the mysteries of
      the genome, the promise of discarding generic treatment regimens in favor of
      patient-specific therapies became more feasible and realistic. One of the major
      scientific impediments of this movement towards personalized medicine has been
      the need for technological enablement. Nanotechnology is projected to play a
      critical role in patient-specific therapy; however, this transition will depend
      heavily upon the evolutionary development of a systems biology approach to
      clinical medicine based upon "-omic" technology analysis and integration. This
      manuscript provides a forward looking assessment of the promise of nanomedicine
      as it pertains to individualized medicine and establishes a technology "snapshot"
      of the current state of nano-based products over a vast array of clinical
      indications and range of patient specificity. Other issues such as market driven
      hurdles and regulatory compliance reform are anticipated to "self-correct" in
      accordance to scientific advancement and healthcare demand. These peripheral, non
      scientific concerns are not addressed at length in this manuscript; however they
      do exist, and their impact to the paradigm shifting healthcare transformation
      towards individualized medicine will be critical for its success.

PMID- 20045063
TI  - A novel gene of tumor necrosis factor ligand superfamily from kuruma shrimp,
      Marsupenaeus japonicus.
AB  - A tumor necrosis factor (TNF) gene has been isolated and characterized in kuruma
      shrimp, Marsupenaeus japonicus, providing the first conclusive evidence for the
      existence of the TNF ligand in shrimp. The kuruma shrimp TNF (MjTNF) cDNA was
      composed of 1868 bp with a 262 bp 5'-untranslated region (UTR) and a 220 bp 3'
      UTR, which was translated into a protein of 462 amino acid residues that included
      a predicted transmembrane domain of 23 amino acid residues (Trp20-Val42) and the
      TNF family signature (Pro321-Leu448). Homology analysis of MjTNF showed 30.7% and
      26.7% identities with fruit fly (Drosophila melanogaster) Eiger and human (Homo
      sapiens) ectodysplasin A, respectively. The MjTNF gene was constitutively
      expressed in unstimulated organs of shrimp such as the muscle, stomach, brain and
      gill. In lymphoid organ cells, an enhanced expression of the MjTNF gene was
      observed following stimulation with peptidoglycan and polycytidylic acid. A high
      expression level of MjTNF was observed in vivo 2 h and 4 h after stimulation with
      lipopolysaccharide and Vibrio penaeicida, respectively. These observations
      suggest that MjTNF plays a role in the innate immune defense in kuruma shrimp.
      The discovery of shrimp TNF will allow a more complete and concrete understanding
      of shrimp inflammatory responses.

PMID- 20045064
TI  - Ferritin administration effectively enhances immunity, physiological responses,
      and survival of Pacific white shrimp (Litopenaeus vannamei) challenged with white
      spot syndrome virus.
AB  - We examined the physiological (hemolymph glucose, lactate, and lipid) and innate
      non-specific immune responses (total hemocyte count (THC), phenoloxidase (PO)
      activity, respiratory bursts (release of superoxide anion, O(2)(-)) and
      superoxide dismutase (SOD) activity) to white spot syndrome virus (WSSV) in white
      shrimp (Litopenaeus vannamei) that were individually injected with 0.1, 0.5, and
      1 ng g(-1) ferritin. Results showed that the THC, PO activity, and respiratory
      bursts of L. vannamei obviously increased (p < 0.05) 12 h after being injected
      with any dose of ferritin. However, the THC, PO activity, and respiratory bursts
      of L. vannamei that had received 0.5 and 1 ng g(-1) ferritin were significant
      higher than those of the other groups at 36-60, 60-72, and 36-60 h, respectively.
      SOD activities of L. vannamei 12 h after receiving 0.1, 0.5, and 1 ng g(-1)
      ferritin were significantly higher than those receiving saline. L. vannamei
      injected with ferritin at any dose maintained lower glucose, lactate, and lipid
      levels in response to WSSV challenge after 12-36, 24-48, and 36-60 h,
      respectively. The survival of shrimp that had received 0.5 and 1 ng g(-1)
      ferritin was significantly higher than that of shrimp that received saline and of
      control shrimp after 72 h. The ferritin messenger RNA transcripts of shrimp that
      had received 0.5 and 1 ng g(-1) ferritin were significantly higher than that of
      shrimp that received saline after 36 h. It was, therefore, concluded that the
      immune ability and resistance against WSSV infection increased in L. vannamei
      that had received > 0.5 ng g(-1) ferritin. Ferritin does play important roles in
      the innate immunity of the white shrimp. We observed higher SOD activities of L.
      vannamei that had received 0.1, 0.5, and 1 ng ferritin after 12 h than those that
      had received only saline (control), and the high SOD expression remained at the
      same levels even after 72 h of treatment.

PMID- 20045065
TI  - Molecular cloning and characterization of peptidoglycan recognition proteins from
      the rockfish, Sebastes schlegeli.
AB  - Peptidoglycan recognition proteins (PGRPs) are innate immune molecules that are
      structurally conserved through evolution in both invertebrate and vertebrate
      animals. Here we report the identification and characterization of two long forms
      of PGRP (SsPGRP-L1 and SsPGRP-L2) from the rockfish, Sebastes schlegeli. The
      deduced amino acid sequences of SsPGRP-L1 and SsPGRP-L2, 466 and 482 residues
      respectively, contain the conserved PGRP domain and the four Zn(2+)-binding amino
      acid residues required for amidase activity. In addition to peptidoglycan-lytic
      amidase activity, recombinant SsPGRPs have broad-spectrum antimicrobial activity
      like zebrafish PGRPs. RT-PCR analysis of total RNA shows that the expression
      patterns of SsPGRP-L1 and SsPGRP-L2 genes are different, though they are widely
      expressed in the tissues that come in contact with bacteria. Overall, these data
      suggest that rockfish PGRPs are involved in the innate host defense of S.
      schlegeli against bacterial infections.

PMID- 20045066
TI  - Expression of Mytilus immune genes in response to experimental challenges varied
      according to the site of collection.
AB  - Mussels live in diverse coastal environments experience various physical,
      chemical and biological conditions, which they counteract with functional
      adjustments and heritable adaptive changes. In order to investigate possible
      differences in immune system capabilities, we analyzed by qPCR the expression
      levels of 4 immune genes (defensin, mytilin B, myticin B, lysozyme) and HSP70 in
      the Mediterranean mussel, Mytilus galloprovincialis collected in 3 European
      farming areas {Atlantic Ocean-Ria de Vigo-Spain (RV), French Mediterranean Gulf
      of Lion-Palavas-Prevost lagoon (PP) and Northern Adriatic Sea-Venice-Italy (VI)}
      in response to one injection of one of the 3 bacterial species (Vibrio splendidus
      LGP32, Vibrio anguillarum, Micrococcus lysodeikticus), and to heat shock or cold
      stress. We confirmed that the 5 genes are constitutively expressed in hemocytes,
      defensin being the less expressed, myticin B the highest. As suspected, the same
      gene resulted differently expressed according to mussel group, with the biggest
      difference being for HSP70 and lysozyme and lowest expression of all the 5 genes
      in mussels from RV. In addition, gene expression levels varied according to the
      challenge. Most frequent effect of bacterial injections was down-regulation,
      especially for mytilin B and myticin B. Heat shock enhanced transcript levels,
      particularly in mussels from RV, whereas cold stress had no effect. In situ
      hybridization of labelled probes on mussel hemocytes indicated that bacterial
      injections did not change the mRNA patterns of defensin and myticin B whereas
      mytilin B mRNA almost disappeared. In conclusion, these results demonstrated that
      constitutive level, nature and intensity of immune gene expression regulations
      strongly depended from mussel group, and support the concept of gene-environment
      interactions.

PMID- 20045067
TI  - Brain activation during interference resolution in young and older adults: an
      fMRI study.
AB  - A rapid event-related fMRI arrow flanker task was used to study aging-associated
      decline in executive functions related to interference resolution. Older adults
      had more difficulty responding to Incongruent cues during the flanker task
      compared to the young adults; the response time difference between the
      Incongruent and Congruent conditions in the older group was over 50% longer
      compared to the young adults. In the frontal regions, differential activation
      ("Incongruent-Congruent" conditions) was observed in the inferior and middle
      frontal gyri in within-group analyses for both groups. However, the cluster was
      smaller in the older group and the centroid location was shifted by 19.7 mm. The
      left superior and medial frontal gyri also appeared to be specifically recruited
      by older adults during interference resolution, partially driven by errors. The
      frontal right lateralization found in the young adults was maintained in the
      older adults during successful trials. Interestingly, bilateral activation was
      observed when error trials were combined with successful trials highlighting the
      influence of brain activation associated with errors during cognitive processing.
      In conclusion, aging appears to result in modified functional regions that may
      contribute to reduced interference resolution. In addition, error processing
      should be considered and accounted for when studying age-related cognitive
      changes as errors may confound the interpretation of task specific age-related
      activation differences.

PMID- 20045068
TI  - Bifurcation analysis of neural mass models: Impact of extrinsic inputs and
      dendritic time constants.
AB  - Neural mass models (NMMs) explain dynamics of neuronal populations and were
      designed to strike a balance between mathematical simplicity and biological
      plausibility. They are currently widely used as generative models for noninvasive
      electrophysiological brain measurements; that is, magneto- and
      electroencephalography (M/EEG). Here, we systematically describe the oscillatory
      regimes which a NMM of a single cortical source with extrinsic input from other
      cortical and subcortical areas to each subpopulation can explain. For this
      purpose, we used bifurcation analysis to describe qualitative changes in system
      behavior in response to quantitative input changes. This approach allowed us to
      describe sequences of oscillatory regimes, given some specific input trajectory.
      We systematically classified these sequential phenomena and mapped them into
      parameter space. Our analysis suggests a principled scheme of how complex M/EEG
      phenomena can be modeled parsimoniously on two time scales: While the system
      displays fast oscillations, it slowly traverses phase space to another
      qualitatively different oscillatory regime, depending on the input dynamics. The
      resulting scheme is useful for applications where one needs to model an ordered
      sequence of switching between qualitatively different oscillatory regimes, for
      example, in pharmacological interventions, epilepsy, sleep, or context-induced
      state changes.

PMID- 20045070
TI  - Semantic interference in object naming: an fMRI study of the postcue naming
      paradigm.
AB  - It is well established that the time to name target objects can be influenced by
      the presence of categorically related versus unrelated distractor items. A
      variety of paradigms have been developed to determine the level at which this
      semantic interference effect occurs in the speech production system. In this
      study, we investigated one of these tasks, the postcue naming paradigm, for the
      first time with fMRI. Previous behavioural studies using this paradigm have
      produced conflicting interpretations of the processing level at which the
      semantic interference effect takes place, ranging from pre- to post-lexical. Here
      we used fMRI with a sparse, event-related design to adjudicate between these
      competing explanations. We replicated the behavioural postcue naming effect for
      categorically related target/distractor pairs, and observed a corresponding
      increase in neuronal activation in the right lingual and fusiform gyri-regions
      previously associated with visual object processing and colour-form integration.
      We interpret these findings as being consistent with an account that places the
      semantic interference effect in the postcue paradigm at a processing level
      involving integration of object attributes in short-term memory.

PMID- 20045069
TI  - A unique role for the human amygdala in novelty detection.
AB  - Previous research indicates that the amygdala and hippocampus are sensitive to
      novelty; however, two types of novelty can be distinguished - stimuli that are
      ordinary, but novel in the current context, and stimuli that are unusual. Using
      functional magnetic resonance imaging, we examined blood oxygen dependent level
      (BOLD) response of the human amygdala and hippocampus to novel, commonly seen
      objects versus novel unusual objects. When presented with the novel common
      stimuli, the BOLD signal increased significantly in both the amygdala and
      hippocampus. However, for the novel unusual stimuli, only the amygdala showed an
      increased response compared to the novel common stimuli. These findings suggest
      that the amygdala is distinctly responsive to novel unusual stimuli, making a
      unique contribution to the novelty detection circuit.

PMID- 20045071
TI  - The generation of rhythms within a cortical region: analysis of a neural mass
      model.
AB  - Rhythms in brain electrical activity are assumed to play a significant role in
      many cognitive and perceptual processes. It is thus of great value to analyze
      these rhythms and their mutual relationships in large scale models of cortical
      regions. In the present work, we modified the neural mass model by Wendling et
      al. (Eur. J. Neurosci. 15 (2002) 1499-1508) by including a new inhibitory self
      loop among GABAA,fast interneurons. A theoretical analysis was performed to
      demonstrate that, thanks to this loop, GABAA,fast interneurons can produce a
      gamma rhythm in the power spectral density (PSD) even without the participation
      of the other neural populations. Then, the model of a whole cortical region,
      built upon four interconnected neural populations (pyramidal cells, excitatory,
      GABAA,slow and GABAA,fast interneurons) was investigated by changing the internal
      connectivity parameters. Results show that different rhythm combinations (beta
      and gamma, alpha and gamma, or a wide spectrum) can be obtained within the same
      region by simply altering connectivity values, without the need to change
      synaptic kinetics. Finally, two or three cortical regions were connected by using
      different topologies of long range connections. Results show that long-range
      connections directed from pyramidal neurons to GABAA,fast interneurons are the
      most efficient to transmit rhythms from one region to another. In this way, PSD
      with three or four peaks can be obtained using simple connectivity patterns. The
      model can be of value to gain a deeper insight into the mechanisms involved in
      the generation of gamma rhythms and provide a better understanding of cortical
      EEG spectra.

PMID- 20045072
TI  - Diffusion tensor anisotropy in the cingulate gyrus in schizophrenia.
AB  - It has been proposed that schizophrenia results partly from altered brain
      connectivity. The anterior cingulate cortex in particular has been demonstrated
      to be affected in schizophrenia, with studies reporting reduced volume, altered
      neuronal arrangement, decreased anisotropy in diffusion tensor images, and
      hypometabolism. We used a 3T Siemens scanner to acquire structural and diffusion
      tensor imaging in age-and sex-matched groups of 41 adults with chronic
      schizophrenia, 6 adults with recent-onset schizophrenia, and 38 healthy control
      subjects. We manually traced the anterior and posterior cingulate gyri on all
      subjects and then compared the volume and anisotropy across groups for the left
      and right anterior and posterior cingulate gyri. The anterior cingulate gyrus was
      divided axially into six equal segments, and the posterior cingulate gyrus into
      two segments. Volume was calculated for the anterior and posterior gyri, and
      average anisotropy was then calculated for each individual segment, looking
      separately at gray and white matter. We found decreased overall relative left and
      right gray matter volume in the anterior cingulate gyrus in persons with
      schizophrenia compared with healthy controls. Additionally, in both gray and
      white matter of the cingulate, we found that recent-onset patients had the
      highest anisotropy, chronic patients had the lowest, and controls were
      intermediate. These results provide additional evidence for the presence of both
      white and gray matter abnormalities in the cingulate gyrus, which has been
      implicated in schizophrenia.

PMID- 20045073
TI  - Limited effects of among-lineage rate variation on the phylogenetic performance
      of molecular markers.
AB  - Variation in substitution rates among evolutionary lineages (among-lineage rate
      variation or ALRV) has been reported to negatively affect the estimation of
      phylogenies. When the substitution processes underlying ALRV are modeled
      inadequately, non-sister taxa with similar substitution rates are estimated
      incorrectly as sister species due to long-branch attraction. Recent advances in
      modeling site-specific rate variation (heterotachy) have reduced the impacts of
      ALRV on phylogeny estimation in several empirical and simulated datasets.
      However, the addition of parameters to the substitution model reduces power to
      estimate each parameter correctly, which can also lead to incorrect phylogeny
      estimation. A potential solution to this problem is to identify the levels of
      ALRV that negatively impact phylogeny estimation such that molecular markers with
      non-deleterious levels of ALRV can be identified. To this end, we used analyses
      of empirical and simulated gene datasets to evaluate whether levels of ALRV
      identified in a mitochondrial genomic dataset for salamanders negatively impacted
      phylogeny estimation. We simulated data with and without ALRV, holding all other
      evolutionary parameters constant, and compared the phylogenetic performance of
      both simulated and empirical datasets. Overall, we found limited, positive
      effects of ALRV on phylogeny estimation in this dataset, the majority of which
      resulted from an increase in substitution rate on short branches. We conclude
      that ALRV does not always negatively impact phylogeny estimation. Therefore, ALRV
      can likely be disregarded as a criterion for marker selection in comparable
      phylogenetic studies.

PMID- 20045074
TI  - Phylogenetic relationships within the lophophorate lineages (Ectoprocta,
      Brachiopoda and Phoronida).
AB  - We produced two new EST datasets of so far uncovered clades of ectoprocts to
      investigate the phylogenetic relationships within the lophophorate lineages,
      Ectoprocta, Brachiopoda and Phoronida. Maximum-likelihood analyses based on 78
      ribosomal proteins of 62 metazoan taxa support the monophyly of Ectoprocta and a
      sister group relationship of Phylactolaemata living in freshwater and the mainly
      marine Gymnolaemata. Hypotheses suggesting that Ectoprocta is diphyletic with
      phylactolaemates forming a clade with phoronids or paraphyletic with respect to
      Entoprocta could be rejected by topology tests. The hypotheses that Stenolaemata
      are the sister group of all other ectoprocts, that Stenolaemata constitutes a
      monophyletic group with Cheilostomata, and that Phylactolaemata have been derived
      from Ctenostomata could also be excluded. However, the hypothesis that
      Phylactolaemata and Stenolaemata form a monophyletic group could not be rejected.
      Brachiopoda and Phoronida constitute a monophylum, Brachiozoa. The hypotheses
      that phoronids are the sister group of articulate or inarticulate brachiopods
      could be rejected by topology tests, thus confirming the monophyly of
      Brachiopoda.

PMID- 20045075
TI  - Acute effects of alcohol on memory: impact of emotional context and serial
      position.
AB  - Although the amnestic effects of alcohol in humans are well known, its effects on
      emotional memory are unclear. In this study, using a randomized double-blind
      placebo-controlled design, we examine narrative emotional episodic memory in
      healthy human female volunteers (n=32) who received either a single dose of
      alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented
      in either a neutral or emotional context. Memory was tested for gist and detail
      of the neutral elements 3days later in a surprise recognition test. Since alcohol
      modulates GABAergic neurotransmission and may exert its effects on emotion
      through the limbic system, we predicted that acute alcohol treatment would reduce
      the expected emotional memory-advantage for gist, leaving detail memory
      relatively unaffected. Furthermore, given previous findings showing that
      'primacy' memory is enhanced by physiological arousal, we predicted that reduced
      arousal produced by alcohol would have the opposite effect and impair primacy
      memory relative to the middle or 'recency' sections of the narrative. Emotional
      arousal was expected to oppose this effect, so impaired primacy memory following
      alcohol was only expected in the neutral version of the narrative. Although there
      was a main effect of story phase (though not of story version), contrary to
      expectations, alcohol impaired primacy memory for emotionally encoded neutral
      material. The results suggest that under certain circumstances emotional context
      or physiological arousal make memories labile and susceptible to disruption
      through pharmacological manipulation during encoding.

PMID- 20045076
TI  - Experience-dependent alterations in conscious resting state activity following
      perceptuomotor learning.
AB  - In monkeys and rats, neural activity patterns during learning are reactivated
      during subsequent periods of rest or sleep. According to the reactivation
      consolidation account, this process underlies the consolidation of memories.
      Brain imaging studies have extended these findings to humans during sleep, but
      not yet, during rest. Here, we show that learning-related reactivation also
      occurs in humans during rest. During functional MRI-scanning, participants
      trained on a perceptuomotor task flanked by rest periods. During training, we
      found robust activity in the superior parietal cortex. During post-training rest,
      this same area reactivated. We also found a link between parietal reactivation
      and learning. Activity in superior parietal cortex was associated with learning
      during training, and a control group that did not train on the perceptuomotor
      task did not show any difference between the pre- and post-training rest blocks
      in this region. These findings indicate that, during rest, reactivation also
      occurs in humans. This process may contribute to consolidation of perceptuomotor
      memories.

PMID- 20045077
TI  - OPA1 (dys)functions.
AB  - Mitochondrial morphology varies according to cell type and cellular context from
      an interconnected filamentous network to isolated dots. This morphological
      plasticity depends on mitochondrial dynamics, a balance between antagonistic
      forces of fission and fusion. DRP1 and FIS1 control mitochondrial outer membrane
      fission and Mitofusins its fusion. This review focuses on OPA1, one of the few
      known actors of inner membrane dynamics, whose mutations provoke an optic
      neuropathy. Since its first identification in 2000 the characterization of the
      functions of OPA1 has made rapid progress thus providing numerous clues to
      unravel the pathogenetic mechanisms of ADOA-1.

PMID- 20045079
TI  - Functional characterization of lysophosphatidic acid phosphatase from Arabidopsis
      thaliana.
AB  - Lysophosphatidic acid (LPA) acts as a signaling molecule that regulates diverse
      cellular processes and it can rapidly be metabolized by phosphatase and
      acyltransferase. LPA phosphatase gene has not been identified and characterized
      in plants so far. The BLAST search revealed that the At3g03520 is similar to
      phospholipase family, and distantly related to bacterial phosphatases. The
      conserved motif, (J)4XXXNXSFD, was identified in both At3g03520 like
      phospholipases and acid phosphatases. In silico expression analysis of At3g03520
      revealed a high expression during phosphate starvation and abiotic stresses. This
      gene was overexpressed in Escherichia coli and shown to posses LPA specific
      phosphatase activity. These results suggest that this gene possibly plays a role
      in signal transduction and storage lipid synthesis.

PMID- 20045078
TI  - Dynein at the kinetochore: Timing, Interactions and Functions.
AB  - Kinetochores have been proposed to play multiple roles in mitotic chromosome
      alignment, including initial microtubule (MT) capture, monitoring MT attachments,
      prometaphase and anaphase chromosome movement and tension generation at
      metaphase. In addition, kinetochores are essential components of the spindle
      assembly checkpoint (SAC), and couple chromosome alignment with SAC silencing at
      metaphase. Although the molecular details of these activities remain under
      investigation, cytoplasmic dynein has been implicated in several aspects of MT
      and SAC regulation. Recent work clarifies the contribution of dynein to MT
      interactions and to events that drive anaphase onset. This review summarizes
      these studies and provides new models for dynein function.

PMID- 20045080
TI  - Special issue on lipotoxicity.

PMID- 20045082
TI  - Alteration in hemodynamic effects of interleukin 2 after treatment with
      indomethacin in anesthetized rats.
AB  - The cardiovascular effects of interleukin 2 (IL2), were investigated in animals
      pretreated with indomethacin. Bolus intravenous administration of IL2 alone
      caused a significant reduction in cardiac output over time. Pretreatment with
      indomethacin significantly accentuated the reduction in cardiac output produced
      by IL2. The administration of IL2 or indomethacin alone or combined had no
      significant effects on dP/dt, heart rate or plasma troponin levels. As well,
      administration of either compound alone or combined had limited effects on mean
      circulatory filling pressure and arterial blood pressure. Injection of IL2 alone
      significantly increased resistance to venous return and arterial resistance at 3h
      post injections. Pretreatment with indomethacin caused IL2 to produce a
      significantly greater increase in arterial resistance and resistance to venous
      return. Administration of IL2 and indomethacin combined also produced significant
      reduction in stroke volume than IL2 or indomethacin alone. The injection of IL2
      or indomethacin alone or combined had no significant impact on blood volume.
      Acute administration of IL2 appears to have no negative inotropic or chronotropic
      effects and its impact in reducing cardiac output is the result of an increase in
      vascular resistance. It seems that activation of prostanoids, possibly
      prostacyclin, has an acute beneficial effect in attenuating the initial negative
      effects of IL2 on cardiac output.

PMID- 20045083
TI  - Cardiovascular and respiratory reflexes of the gulf toadfish (Opsanus beta)
      during acute hypoxia.
AB  - The acute cardiovascular and respiratory responses of the gulf toadfish, Opsanus
      beta, to acute hypoxia or exposure to the O(2) chemoreceptor stimulant, sodium
      cyanide (NaCN) were characterized and the role of serotonin type 2 (5-HT(2))
      receptors in mediating these responses was investigated. Toadfish responded to
      hypoxia or NaCN exposure with a decrease in heart rate (fH) and an increase in
      breathing amplitude (V(AMP)) but no change in breathing frequency (fR). The
      bradycardia appeared to be mediated to some extent by 5-HT(2) receptors, as
      methysergide, a non-selective 5-HT(1/2) receptor antagonist, and ketanserin, a 5
      HT(2) receptor antagonist, attenuated the response. Injection of alpha-methyl-5
      HT, a 5-HT(2) agonist, also resulted in bradycardia that was inhibited by
      ketanserin, lending further support for 5-HT(2) receptor involvement, possibly 5
      HT(2A) or 5-HT(2C), in the regulation of fH. External NaCN exposure resulted in a
      significant decrease in caudal arterial blood pressure (P(CA)) that was
      attenuated by methysergide. In contrast, injection with alpha-methyl-5-HT
      resulted in a substantial increase in P(CA) that was not affected by ketanserin,
      suggesting the possible involvement of 5-HT(2B) or 5-HT(2C) receptors. These data
      are the first to suggest a unique distribution of 5-HT(2B/2C) receptors may be
      involved in mediating vasoconstriction of the systemic vasculature of toadfish.
      These data also provide mechanistic support for why pulsatile urea excretion,
      believed to be regulated by 5-HT via the toadfish 5-HT(2A) receptor, is not
      triggered by hypoxia or external chemoreceptor activation.

PMID- 20045081
TI  - Molecular mechanisms involved in adenosine-induced endothelial cell barrier
      enhancement.
AB  - Extracellular adenosine is a physiologically relevant agonist released by various
      sources, including endothelial cells (EC) and activated platelets, with complex
      effects mediated via activation of P1 purinergic receptors. Adenosine-induced EC
      production of glutathione peroxidase1 and nitric oxide is recognized, and an anti
      inflammatory mechanism has been described. Effects of extracellular adenosine on
      the pulmonary EC barrier function and vascular permeability, however, remain
      poorly characterized. In this study, we demonstrated the adenosine-induced rapid
      dose-dependent barrier enhancement in human pulmonary artery EC (HPAEC) as
      measured by an increase in transendothelial electrical resistance (TER). We have
      shown that HPAEC express only A2A and A2B adenosine receptors. Pharmacological
      and siRNA depletion studies indicate that A2A, but not A2B receptor activation is
      required for the adenosine-induced TER increase. Depletion of Galphas with a
      specific siRNA significantly attenuated the adenosine-induced TER response in
      HPAEC. In contrast, depletion of either Galphaq or Galphai2 did not affect the
      adenosine-induced TER increase. This suggests that the adenosine-induced TER
      increase is cAMP-dependent. The adenosine-induced barrier enhancement effects
      were associated with a rearrangement of the EC F-actin component of the
      cytoskeleton, enhanced cell-surface presentation of cell-cell junctional protein
      VE-cadherin and an involvement of Myosin-light-chain phosphatase (MLCP). Our
      results suggest, for the first time, that adenosine regulates the EC barrier
      function via A2A receptors followed by Galphas engagement and is associated with
      cytoskeletal activation.

PMID- 20045084
TI  - Mass spectrometer for respiratory research.
AB  - The mass spectrometer is the ideal gas analyser for many applications in
      respiratory research. A number of companies which manufactured mass spectrometers
      suitable for use in respiratory research have long since ceased production. Two
      modifications in the presently manufactured MAX300-LG (Extrel, Pittsburgh, PA,
      USA) have made it suitable for studying respiratory physiology. The initial step
      was to bypass the four-port valve and connect the sampling capillary directly to
      the roughing pump. The second step was to replace the original capillary, which
      had an internal diameter of 0.4mm, by a 2-m long capillary having an internal
      diameter of 0.15 mm. The 90% response time was shortened to 85 ms, which is
      suitable for respiratory research.

PMID- 20045085
TI  - Chaperonin-encapsulation of proteins for NMR.
AB  - A novel chaperonin-encapsulation system for NMR measurements has been designed.
      The single-ring variant SR398 with an ATPase deficient mutation of GroEL, also
      known as chaperonin, bound co-chaperonin GroES irreversibly, forming a stable
      cage to encapsulate a target protein. A small GroEL-binding tag made it possible
      to perform all steps of the encapsulation under near physiological conditions
      while retaining the native conformation of the target protein. About half of the
      SR398/GroES cages encapsulated target protein molecules. As binding only depends
      on the 12-residue tag sequence, this encapsulation method is applicable to a
      large number of proteins. Isolation of the target proteins in the molecular cage
      of chaperonin will allow the study of highly aggregation-prone proteins by
      solution NMR.

PMID- 20045086
TI  - Coupling effects of distal loops on structural stability and enzymatic activity
      of Escherichia coli dihydrofolate reductase revealed by deletion mutants.
AB  - Residues distal from the active site in dihydrofolate reductase (DHFR) have
      regulatory roles in catalytic reaction and also folding stability. The couplings
      of the distal residues to the ones in the active site have been analyzed using
      site-directed mutants. To expand our understanding of the structural and
      functional influences of distal residue mutation, we explored the structural
      stability and enzymatic activity of deletion mutants. Deletion has greater
      structural and dynamical impacts on the corresponding part than site-directed
      mutation does. Thus, deletion amplifies the effects caused by distal mutations,
      which should make the mutual couplings among the distant residues more apparent.
      We focused on residues 52, 67, 121, and 145 in the four distinct loops of DHFR.
      All the single-residue deletion mutants showed marked reduction in stability,
      except for Delta52 in an alphaC-betaC loop. Double deletion mutants showed that
      the loop alphaC-betaC has nonadditive couplings with the betaF-betaG and betaG
      betaH loops regarding stability. Single deletion to the loops alphaC-betaC or
      betaC-betaD resulted in considerable activity reduction, demonstrating that the
      loops couple to the residues near the active site. The four loops were shown to
      be functionally interdependent from the double deletion experiments.

PMID- 20045087
TI  - Microtopographically patterned surfaces promote the alignment of tenocytes and
      extracellular collagen.
AB  - This paper investigates the role of microtopographical features on the
      cytomorphology, alignment, proliferation and gene expression of tenocytes. We
      made use of simple microfabrication approaches to create surfaces patterned with
      topographical features suitable for in vitro studies of tenocytes. These surfaces
      were composed of glass substrates patterned with polymeric ridges spaced from 50
      to 250 microm apart. Our studies demonstrate that the microgrooves differentially
      impact tenocyte shape, alignment and matrix organization along the direction of
      grooves. Groove widths significantly influenced cellular alignment, with 50
      microm grooved patterns affecting alignment most substantially. Polarized light
      microscopy demonstrated that mature collagen fibers were denser and more oriented
      within 50 microm patterns. None of the patterns had a significant effect on the
      expression of genes linked to proliferation or extracellular matrix synthesis,
      although time in culture profoundly influenced both gene groups. COMP mRNA
      expression was moderately increased in tenocytes seeded onto 250 microm grooves,
      but there was no overall beneficial phenotypic effect of aligned growth. The
      results of this study indicate that microtopography affects cell density and
      alignment of tenocytes and leads to the deposition of an aligned collagen matrix,
      but does not significantly impact matrix gene expression or cell phenotype. These
      outcomes provide insights into the biology of tendon regeneration, thus providing
      guidance in the design of clinical procedures for tendon repair.

PMID- 20045088
TI  - Open volume in bioadhesive detected by positron annihilation lifetime
      spectroscopy.
AB  - Barnacles attach to a wide variety of surfaces underwater and show substrate
      specific adhesion mechanisms. Investigating and understanding these mechanisms is
      a key for developing new technical adhesives. We expected open volume (porosity)
      at the sub-nanometre scale to occur in barnacle adhesive. With positron
      annihilation lifetime spectroscopy (PALS) it is possible to detect porosity at
      the nanometre scale by determining the lifetime of positrons. This method has not
      been applied to bioadhesives so far. We showed that PALS is a suitable technique
      for the investigation of the barnacle base and its adhesive with respect to open
      volume. The results were interpreted using a standard model adapted from
      polymers. We thereby estimated pore sizes of 0.5 nm.

PMID- 20045089
TI  - Cellular activity of bioactive nanograined/ultrafine-grained materials.
AB  - Our recent electron microscopy study on biomimetic nanostructured coatings on
      nanograined/ultrafine-grained (NG/UFG) substrates [Mater Sci Eng C 2009;29:2417
      27] indicated that electrocrystallized nanohydroxyapatite (nHA) on phase
      reversion-induced NG/UFG substrates exhibited a vein-type interconnected and
      fibrillar structure that closely mimicked the hierarchical structure of bone. The
      fibrillar structure on NG/UFG substrate is expected to be more favorable for
      cellular response than a planar surface. In contrast, hydroxyapatite (HA) coating
      on coarse-grained (CG) substrate more closely resembled a film rather than a
      fibrillar structure. Inspired by the differences in the structure of HA coating,
      we describe here the cell-substrate interactions of pre-osteoblasts (MC 3T3-E1)
      on bioactive NG/UFG and CG austenitic stainless steel substrates. NG/UFG
      austenitic stainless steel was obtained by a novel controlled phase-reversion
      annealing of cold-deformed austenite. This example provides an illustration of
      how a combination of cellular and molecular biology, materials science and
      engineering can advance our understanding of cell-substrate interactions.
      Interestingly, the cellular response of nanohydroxyapatite (nHA)-coated NG/UFG
      substrate demonstrated superior cytocompatibility, improved initial cell
      attachment, higher viability and proliferation, and well-spread morphology in
      relation to HA-coated CG substrate and their respective uncoated (bare)
      counterparts as implied by fluorescence and electron microscopy and MTT assay.
      Similar conclusions were derived from an immunofluorescence study that involved
      examination of the expression levels of vinculin focal adhesion contacts
      associated with dense actin stress fibers and fibronectin, protein analysis
      through protein bands in SDS-PAGE, and quantitative total protein assay. The
      enhancement of cellular response followed the sequence: nHA-coated NG/UFG>nHA
      coated CG>NG/UFG>CG substrates. The outcomes of the study are expected to counter
      the challenges associated with the engineering of nanostructured surfaces with
      specific physical and surface properties for medical devices with significantly
      improved cellular response.

PMID- 20045090
TI  - Blood compatibility of photografted hydrogel coatings.
AB  - In this work, we have evaluated the haemocompatibility of different surface
      modifications, intended for biomaterials and bioanalytical applications.
      Polystyrene slides were coated with thin hydrogel films by self-initiated
      photografting and photopolymerization (SIPGP) of four different monomers. The
      hydrogel surface modifications were thoroughly characterized and tested for their
      protein resistance and ability to resist platelet adhesion and activation of the
      coagulation system. There was very little protein adsorption from human plasma on
      the hydrogels prepared from poly(ethylene glycol) methacrylate and 2-hydroxyethyl
      methacrylate. Platelet adhesion tests performed under both static and flow
      conditions showed that these coatings also demonstrated very high resistance
      towards platelet adhesion. A small amount of platelets were found to adhere to
      hydrogels formed from ethylene glycol methyl ether methacrylate and 2
      carboxyethyl methacrylate. The polystyrene substrates themselves facilitated
      large amounts of platelet adhesion under both static and flow conditions.
      Utilizing a novel setup for imaging of coagulation, it was confirmed that none of
      the hydrogel surfaces activated the coagulation system to any great extent. We
      suggest that this simple fabrication method can be used to produce hydrogel
      coatings with unusually high blood compatibility, suitable for demanding
      biomaterials applications.

PMID- 20045091
TI  - Enhanced bone formation using hydroxyapatite ceramic coated with fibroblast
      growth factor-2.
AB  - Our objective was to develop a bone substitute coated with fibroblast growth
      factor-2 (FGF-2) that subsequently releases FGF-2. We investigated the use of our
      system of bone substitutes to induce bone formation. Hydroxyapatite ceramic
      buttons (HAP-CBs) were coated with FGF-2 by precipitation in supersaturated
      calcium phosphate solution. HAP-CBs were coated with high or low doses of FGF-2,
      denoted as FGF-H and FGF-L. The release of FGF-2 from FGF-H and FGF-L was
      evaluated using its release profile and bioactivity. The efficacy of the
      subsequent bone formation was quantified using rats with round-shaped bone
      defects (5mm in diameter) of the right parietal bone. Group 1 was treated only
      with HAP-CBs, group 2 with HAP-CBs and drops of FGF-2 solution, group 3 with FGF
      L and group 4 with FGF-H. To detect the release of FGF-2 in vivo, the expression
      of bone morphogenic protein-2 (BMP-2) was measured in the defective bone tissue.
      FGF-2 was released in vitro from FGF-H and FGF-L, and maintained its bioactivity.
      Rats treated with FGF-L showed better bone formation than rats from the other
      groups. BMP-2 expression was detected in the defective bone tissues of group 3 at
      14 days, which might indicate in vivo FGF-2 release during this period. A
      specific FGF-2 concentration may be needed for bone formation, and our system can
      release FGF-2 at adequate concentrations to induce bone formation.

PMID- 20045092
TI  - Uneventful pregnancy outcome after enzyme replacement therapy with agalsidase
      beta in a heterozygous female with Fabry disease: A case report.
AB  - No reproductive studies have been performed with enzyme replacement therapy (ERT)
      for Fabry disease (FD, OMIM 301500), a lysosomal storage disorder. Therefore, use
      during pregnancy is theoretically contraindicated. We report the first case of
      agalsidase beta treatment throughout pregnancy. High-range proteinuria remained
      stable and the patient gave birth to a healthy boy after an uncomplicated
      pregnancy. The decision to administer ERT during pregnancy should be made on an
      individual basis, considering the FD status and possible risks.

PMID- 20045093
TI  - Epigenetic regulation of latent HSV-1 gene expression.
AB  - Like other alpha-herpesviruses, Herpes Simplex Virus Type 1 (HSV-1) possesses the
      ability to establish latency in sensory ganglia as a non-integrated, nucleosome
      associated episome in the host cell nucleus. Transcription of the genome is
      limited to the Latency-Associated Transcript (LAT), while the lytic genes are
      maintained in a transcriptionally repressed state. This partitioning of the
      genome into areas of active and inactive transcription suggests epigenetic
      control of HSV-1 latent gene expression. During latency viral transcription is
      not regulated by DNA methylation but likely by post-translational histone
      modifications. The LAT region is the only region of the genome enriched in marks
      indicative of transcriptional permissiveness, specifically dimethyl H3 K4 and
      acetyl H3 K9, K14, while the lytic genes appear under-enriched in those same
      marks. In addition, facultative heterochromatin marks, specifically trimethyl H3
      K27 and the histone variant macroH2A, are enriched on lytic genes during latency.
      The distinct epigenetic domains of the LAT and the lytic genes appear to be
      separated by chromatin insulators. Binding of CTCF, a protein that binds to all
      known vertebrate insulators, to sites within the HSV-1 genome likely prevents
      heterochromatic spreading and blocks enhancer activity. When the latent viral
      genome undergoes stress-induced reactivation, it is possible that CTCF binding
      and insulator function are abrogated, enabling lytic gene transcription to ensue.
      In this review we summarize our current understanding of latent HSV-1 epigenetic
      regulation as it pertains to infections in both the rabbit and mouse models. CTCF
      insulator function and regulation of histone tail modifications will be
      discussed. We will also present a current model of how the latent genome is
      carefully controlled at the epigenetic level and how stress-induced changes to it
      may trigger reactivation.

PMID- 20045094
TI  - Chitosan-based formulations of drugs, imaging agents and biotherapeutics.
      Preface.

PMID- 20045095
TI  - Determinants for HPV vaccine uptake in the Netherlands: A multilevel study.
AB  - In March 2009, a HPV catch-up vaccination campaign was implemented in the
      Netherlands for girls born between 1993 and 1996. We performed a multilevel study
      to investigate determinants for HPV vaccination uptake. National coverage for the
      first dose was 49.9%, with regional uptakes ranging from 31% to 61%. Data was
      gathered from individual to regional level. Our results suggest that organizing
      information meetings at schools and communicating with gynaecologists might be
      beneficial. Lower uptake among various ethnic groups and in areas with higher
      proportion of voters for Religious Political Parties indicate that communication
      on HPV vaccine should be adapted to religious and ethnic communities.
      Furthermore, lower uptake in areas with lower socioeconomic status needs
      attention since participation to cervical screening is also lower in these areas.

PMID- 20045096
TI  - HCV-core and NS3 antigens play disparate role in inducing regulatory or effector
      T cells in vivo: Implications for viral persistence or clearance.
AB  - A distinguishing feature of HCV is its ability to persist in majority of the
      infected people. We investigated the role of HCV-core and NS3 in inducing
      effector T cells to mediate antiviral immunity. Our studies revealed that
      immunization with recombinant adenoviral vector containing HCV-core or NS3 leads
      to differential development of regulatory vs. effector T cells in mice, resulting
      in distinct outcomes of virus infection. For the first time, our studies directly
      demonstrate that HCV-core enhances both CD4(+) and CD8(+) T(regs) which possibly
      contribute to persistent infection, whereas HCV NS3 induces both CD4(+) and
      CD8(+) effector T cells to allow viral clearance.

PMID- 20045097
TI  - One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI)
      protects animals against pathogenic viral challenge.
AB  - To combat variola virus in bioterrorist attacks, it is desirable to develop a
      noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was
      historically used to eradicate the smallpox in China, we generated a modified VTT
      (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region
      from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell
      range in vitro and preclinical safety and efficacy profiles in mice. Despite
      replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause
      death after intracranial injection or body weight loss after intranasal
      inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in
      immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the
      intranasal route of immunization. One time intranasal immunization protected
      animals from the challenge of the pathogenic vaccinia WR strain. This study
      established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve
      as a safe noninvasive smallpox vaccine candidate.

PMID- 20045098
TI  - Dengue v2V--new global initiative supporting transition from vaccine to
      vaccination.

PMID- 20045099
TI  - A postmodern Pandora's box: anti-vaccination misinformation on the Internet.
AB  - The Internet plays a large role in disseminating anti-vaccination information.
      This paper builds upon previous research by analyzing the arguments proffered on
      anti-vaccination websites, determining the extent of misinformation present, and
      examining discourses used to support vaccine objections. Arguments around the
      themes of safety and effectiveness, alternative medicine, civil liberties,
      conspiracy theories, and morality were found on the majority of websites
      analyzed; misinformation was also prevalent. The most commonly proposed method of
      combating this misinformation is through better education, although this has
      proven ineffective. Education does not consider the discourses supporting vaccine
      rejection, such as those involving alternative explanatory models of health,
      interpretations of parental responsibility, and distrust of expertise. Anti
      vaccination protestors make postmodern arguments that reject biomedical and
      scientific "facts" in favour of their own interpretations. Pro-vaccination
      advocates who focus on correcting misinformation reduce the controversy to merely
      an "educational" problem; rather, these postmodern discourses must be
      acknowledged in order to begin a dialogue.

PMID- 20045100
TI  - An especial skill: Support for a learned parameters hypothesis.
AB  - We tested the 'learned parameters' hypothesis as an explanation of the 'especial
      skill effect'. Outcome attainment and movement kinematics were recorded for 10
      expert and 10 novice players performing basketball free-throw shots at five
      distances (11-19 ft) with a regular and heavy weight basketball. As predicted,
      experts performed better than expected relative to the regression equation at the
      15 ft, free-throw line with the regular basketball, supporting the 'especial
      skill effect'. This effect was not present for the experts when shooting with the
      heavy ball. Novices did not show an advantage at the free-throw line when
      performing with either ball. Although the outcome attainment scores support the
      'learned parameters' hypotheses, kinematic analysis failed to identify
      differences in the movement pattern for the especial skill, suggesting that these
      skills (i.e., shooting at different distances) are not governed by separate motor
      programs.

PMID- 20045102
TI  - A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic
      Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease (CMT) is the most common cause of inherited
      peripheral neuropathy, with an estimated frequency of 1/2500. We studied a large
      family with 17 patients affected by the axonal form of CMT (CMT2). Analysis of
      the 15 genes or loci known to date was negative. Genome-wide genotyping
      identified a CMT2 locus in 16q21-q23 between D16S3050 and D16S3106. The maximum
      two-point LOD score was 4.77 at theta = 0 for marker D16S3050. Sequencing of
      candidate genes identified a unique mutation, c.986G>A (p.Arg329His), affecting a
      totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA
      synthetase (AlaRS). A second family with the same mutation and a different
      founder was then identified in a cohort of 91 CMT2 families. Although mislocation
      of mutant Arg329His-AlaRS in axons remains to be evaluated, experimental data
      point mostly to a quantitative reduction in tRNA(Ala) aminoacylation.
      Aminoacylation and editing functions closely cooperate in AlaRS, and Arg329His
      mutation could also lead to qualitative errors participating in
      neurodegeneration. Our report documents in 18 patients the deleterious impact of
      a mutation in human cytoplasmic AlaRS and broadens the spectrum of defects found
      in tRNA synthetases. Patients present with sensory-motor distal degeneration
      secondary to predominant axonal neuropathy, slight demyelination, and no atypical
      or additional CNS features.

PMID- 20045103
TI  - Optimal therapeutic protocols in cancer immunotherapy.
AB  - Using one of the well known mathematical models for immunotherapy of tumor-immune
      interactions, in this paper an algorithm is developed to optimize the
      immunotherapy in cancer treatment. The optimal control strategy is defined to
      maximize the effector cells and interleukin-2 concentration, while minimizing the
      tumor cells. The performance index is developed to stop the growth of tumor cells
      even at the end of the treatment. The maximum principle approach is the optimal
      control strategy in this paper. Analyzing the results and comparing them with
      very recent researches, it is shown that the amount of tumor cells with the
      proposed control algorithm is less then the others, both during and after the
      completion of the treatment.

PMID- 20045104
TI  - Segmentation of the optic disk in color eye fundus images using an adaptive
      morphological approach.
AB  - The identification of some important retinal anatomical regions is a prerequisite
      for the computer aided diagnosis of several retinal diseases. In this paper, we
      propose a new adaptive method for the automatic segmentation of the optic disk in
      digital color fundus images, using mathematical morphology. The proposed method
      has been designed to be robust under varying illumination and image acquisition
      conditions, common in eye fundus imaging. Our experimental results based on two
      publicly available eye fundus image databases are encouraging, and indicate that
      our approach potentially can achieve a better performance than other known
      methods proposed in the literature. Using the DRIVE database (which consists of
      40 retinal images), our method achieves a success rate of 100% in the correct
      location of the optic disk, with 41.47% of mean overlap. In the DIARETDB1
      database (which consists of 89 retinal images), the optic disk is correctly
      located in 97.75% of the images, with a mean overlap of 43.65%.

PMID- 20045105
TI  - Metaphase II human oocyte morphology: contributing factors and effects on
      fertilization potential and embryo developmental ability in ICSI cycles.
AB  - Morphologic abnormalities in the oocyte are relevant for determining its
      developmental fate and could be related to controlled ovarian stimulation
      protocols and ovarian response. The contributing factors of oocyte dysmorphism
      incidence and its effects on fertilization potential and embryo development are
      the object of discussion in this study.

PMID- 20045106
TI  - Erythropoietin protects severe haemorrhagic shock-induced organ damage in
      conscious rats.
AB  - OBJECTIVE: Erythropoietin (EPO) has pleiotropic cytoprotective actions. We
      investigated the effects of EPO on the physiopathology and cytokine levels after
      haemorrhagic shock (HS) in conscious rats. METHODS: Rats received an intravenous
      injection of 300 U/kg EPO over 10 min followed by HS via withdrawal of 60% of
      total blood volume from a femoral arterial catheter (6 ml/100 g body weight) over
      30 min. Mean arterial pressure (MAP) and heart rate (HR) were monitored
      continuously for 18 h after the start of blood withdrawal. Levels of biochemical
      parameters, including haemoglobin, GOT, GPT, BUN, creatinine (Cr), LDH, CPK, and
      lactate were measured at 30 min before the induction of HS and 0, 1, 3, 6, 9, 12,
      and 18 h after HS. Cytokine levels, including TNF-alpha and IL-6, in serum were
      measured at 1, 9, and 18 h after HS. The kidneys, liver, lungs, and small
      intestine were removed for pathology assessment at 48 h after HS. RESULTS: HS
      significantly increased HR, blood GOT, GPT, BUN, Cr, LDH, CPK, lactate, TNF
      alpha, and IL-6 levels and decreased haemoglobin and MAP in rats. Pre-treatment
      with EPO improved survival rate, preserved the MAP, decreased the tachycardia and
      markers of organ injury, suppressed the release of TNF-alpha and IL-6 after HS in
      rats. CONCLUSION: Pre-treatment with EPO suppresses the release of serum TNF
      alpha and IL-6, along with decreasing the levels of markers of organ injury
      associated with HS, with such actions ameliorating HS-induced organ damage in
      rats.

PMID- 20045107
TI  - Court-Brown CM, Clement N. Four score years and ten; an analysis of the
      epidemiology of fractures in the very elderly [Injury 2009;40(October (10)):1111
      4].

PMID- 20045108
TI  - Identification and functional characterization of LDLR mutations in familial
      hypercholesterolemia patients from Southern Italy.
AB  - OBJECTIVE: Autosomal dominant hypercholesterolemias are due to defects in the LDL
      receptor (LDLR) gene, in the apolipoprotein B-100 gene or in the proprotein
      convertase subtilisin/kexin type 9 gene. The aim of this study was to identify
      and functionally characterize mutations in the LDLR gene that account for most
      cases of familial hypercholesterolemia (FH). METHODS: We enrolled 56 unrelated
      patients from Southern Italy with a clinical diagnosis of FH. The mutation
      screening was performed by direct sequencing of the promoter and the 18 exons of
      the LDLR gene and by multiplex ligation-dependent probe amplification (MLPA)
      analysis to search for large rearrangements. RESULTS AND CONCLUSION: We found 5
      new mutations, the causative role of which was demonstrated by functional
      characterization performed by quantification of fluorescent LDL uptake in EBV
      transformed B lymphocytes. These results enlarge the spectrum of FH-causative
      LDLR mutations. Lastly, screening for large rearrangements is highly recommended
      for the genetic diagnosis of FH.

PMID- 20045109
TI  - Apolipoprotein H: its relevance to cardiovascular disease.

PMID- 20045110
TI  - Sleepiness and atherosclerosis in sleep apnea.

PMID- 20045111
TI  - Mechanical properties of the patellar tendon in adults and children.
AB  - It is not currently known how the mechanical properties of human tendons change
      with maturation in the two sexes. To address this, the stiffness and Young's
      modulus of the patellar tendon were measured in men, women, boys and girls (each
      group, n=10). Patellar tendon force (F(pt)) was calculated from the measured
      joint moment during a ramped voluntary isometric knee extension contraction, the
      antagonist knee extensor muscle co-activation quantified from its
      electromyographical activity, and the patellar tendon moment arm measured from
      magnetic resonance images. Tendon elongation was imaged using the sagittal-plane
      ultrasound scans throughout the contraction. Tendon cross-sectional area was
      measured at rest from ultrasound scans in the transverse plane. Maximal F(pt) and
      tendon elongation were (mean+/-SE) 5453+/-307 N and 5+/-0.5 mm for men, 3877+/
      307 N and 4.9+/-0.6 mm for women, 2017+/-170 N and 6.2+/-0.5 mm for boys and
      2169+/-182 N and 5.9+/-0.7 mm for girls. In all groups, tendon stiffness and
      Young's modulus were examined at the level that corresponded to the maximal 30%
      of the weakest participant's F(pt) and stress, respectively; these were 925-1321
      N and 11.5-16.5 MPa, respectively. Stiffness was 94% greater in men than boys and
      84% greater in women than girls (p<0.01), with no differences between men and
      women, or boys and girls (men 1076+/-87 N/mm; women 1030+/-139 N/mm; boys 555+/
      71 N/mm and girls 561.5+/-57.4 N/mm). Young's modulus was 99% greater in men than
      boys (p<0.01), and 66% greater in women than girls (p<0.05). There were no
      differences in modulus between men and women, or boys and girls (men 597+/-49
      MPa; women 549+/-70 MPa; boys 255+/-42 MPa and girls 302+/-33 MPa). These
      findings indicate that the mechanical stiffness of tendon increases with
      maturation due to an increased Young's modulus and, in females due to a greater
      increase in tendon cross-sectional area than tendon length.

PMID- 20045112
TI  - Simple quality assessment approach for herbal extracts using high performance
      liquid chromatography-UV based metabolomics platform.
AB  - A lack of adequate or accepted research methodology has been a major obstacle to
      study herbal medicines. In this study, instead of the prevalent hyphenated
      chromatographies, common high performance liquid chromatography equipped with
      ultraviolet detector (HPLC-UV) and multivariate statistical analysis were
      utilized to assess the qualities of total flavones of sea buckthorn (TFS), an 85%
      ethanol extract of the sea buckthorn berries. Two complementary HPLC-UV methods
      were developed, validated and combined to comprehensively determine the
      ingredients in TFS. Principal component analysis (PCA) and partial least square
      discriminant analysis (PLS-DA) of the combined analytical data showed that the
      six batches of TFS could be well differentiated. Hierarchical cluster analysis
      (HCA) using Ward's minimum variance method of the PLS-DA loading matrix
      demonstrated the known ingredients (quercetin, kaempferol, isorhamnetin,
      oleanolic acid and ursolic acid) and three unknown ingredients in TFS
      significantly contributed to the quality differences. A PLS regression model
      indicated that the results of the present method correlated well with the content
      of total flavones, which is now the quality control approach of TFS. Results from
      this study indicated that the proposed method is reliable for the quality
      reassessment of some widely used herbal extracts.

PMID- 20045101
TI  - Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of
      type 1 diabetes and HIV-1 immune control.
AB  - Abnormal expansion or depletion of particular lymphocyte subsets is associated
      with clinical manifestations such as HIV progression to AIDS and autoimmune
      disease. We sought to identify genetic predictors of lymphocyte levels and
      reasoned that these may play a role in immune-related diseases. We tested 2.3
      million variants for association with five lymphocyte subsets, measured in 2538
      individuals from the general population, including CD4+ T cells, CD8+ T cells,
      CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We
      identified two regions of strong association. The first was located in the major
      histocompatibility complex (MHC), with multiple SNPs strongly associated with
      CD4:CD8 ratio (rs2524054, p = 2.1 x 10(-28)). The second region was centered
      within a cluster of genes from the Schlafen family and was associated with NK
      cell levels (rs1838149, p = 6.1 x 10(-14)). The MHC association with CD4:CD8
      replicated convincingly (p = 1.4 x 10(-9)) in an independent panel of 988
      individuals. Conditional analyses indicate that there are two major independent
      quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one
      is located in the class I cluster and influences CD8 levels, whereas the second
      is located in the class II cluster and regulates CD4 levels. Jointly, both QTL
      explained 8% of the variance in CD4:CD8 ratio. The class I variants are also
      strongly associated with durable host control of HIV, and class II variants are
      associated with type-1 diabetes, suggesting that genetic variation at the MHC may
      predispose one to immune-related diseases partly through disregulation of T cell
      homeostasis.

PMID- 20045113
TI  - Preparation and characterization of novel macroporous cellulose beads regenerated
      from ionic liquid for fast chromatography.
AB  - Macroporous cellulose beads (MCB) used as anion exchangers were successfully
      prepared from cellulose solution in ionic liquid by double emulsification
      followed by cross-linking and modification with diethylaminoethyl. The pore
      structure and properties of the MCB were investigated and the results were
      compared with homogeneous cellulose beads (HCB). The MCB in size of about 71
      microm is characterized by two sets of pores, i.e., diffusion pores (10-20 nm)
      and macropores (800-2000 nm), determined by mercury porosimeter. In addition, the
      bed permeability and effective porosity for BSA of MCB-packed column are 58% and
      25% higher than those of HCB-packed column, respectively. The adsorption
      properties of MCB were evaluated, and compared with HCB and commercial absorbent
      (Sepharose 6 Fast Flow, CSFF). It is found that the pore diffusivity of BSA in
      MCB is over 7.9 times higher than HCB, and 6.7 times higher than CSFF,
      respectively. While the equilibrium adsorption capacity (q(m)) of BSA on MCB is
      obviously lower than that on HCB and CSFF, the dynamic binding capacity (DBC) on
      MCB at 10% breakthrough reaches 47.7 mg/mL, higher than HCB (40.3mg/mL) and CSFF
      (46.2mg/mL) at flow rate of 360 cm/h. In addition, the MCB-packed column showed
      better column efficiency over the HCB packed one. Therefore, we demonstrated that
      the MCB possessed more advantages than other ones, like HCB and CSFF, and was
      expected as an ideal material for fast chromatography.

PMID- 20045114
TI  - Comparison of protein-polysaccharide nanoparticle fabrication methods: impact of
      biopolymer complexation before or after particle formation.
AB  - The nature of protein-polysaccharide nanoparticles prepared using two fabrication
      methods was compared: Type 1 particles were formed by creating beta-lactoglobulin
      nanoparticles, and then coating them with pectin; Type 2 particles were formed by
      heating beta-lactoglobulin and pectin complexes together. Protein nanoparticles
      (d=180 nm) were created by heating beta-lactoglobulin above its thermal
      denaturation temperature (T(m)) at pH 5.8. Type 1 particles were then formed by
      mixing these particles with high methoxy (HM) pectin under conditions where
      pectin adsorbed to the protein (pH<6). Type 2 particles were created by heating
      beta-lactoglobulin-HM pectin electrostatic complexes above T(m) at pH 4.75. At pH
      4.5, Types 1 and 2 particulates had similar charge (-33 mV), protein content, and
      shapes (spheroid), however, Type 1 particulates were larger (d=430 nm) than Type
      2 particulates (d=300 nm). The influence of pH, ionic strength and protein:pectin
      mass ratio (r) on the physical stability of the two types of particles was
      tested. A weight ratio of 2:1 (protein:pectin) gave good pH stability of the
      particles against aggregation by imparting more surface charge. Type 2 particles
      had a higher electrical charge, better stability to aggregation at lower pH
      values (pH<4), and better stability to aggregation at high salt concentrations
      (200 mM NaCl) than Type 1 particles. These differences suggested that Type 2
      particulates had a higher surface coverage with pectin, thereby reducing their
      tendency to aggregate. These results have important consequences for the design
      of biopolymer nanoparticles based on thermal treatment of proteins and
      polysaccharides.

PMID- 20045116
TI  - On the mechanism of patterning in rapidly evaporated polymer solutions: is
      temperature-gradient-driven Marangoni instability responsible for the large-scale
      patterning?
AB  - Large-scale self-organization occurring on the scale of dozens of micrometers in
      rapidly evaporated polymer solutions based on amorphous polymers and chlorinated
      solvents was studied. Heating the substrate from below destroys the patterning.
      This contradicts the idea that self-organization is due to the jump in surface
      tension caused by a temperature gradient (temperature-gradient-driven Marangoni
      instability). We relate the patterning to the concentration-gradient- driven
      effects.

PMID- 20045115
TI  - Surfactant-assisted route to fabricate CoFe2O4 individual nanoparticles and
      spherical assemblies.
AB  - A surfactant-assisted route in aqueous media has been shown to be suitable to
      prepare either individual primary CoFe(2)O(4) nanocrystals or secondary spherical
      nanoporous assemblies with a high surface area. The formation of primary
      nanoparticles or of spherical assemblies is found to be dependent on the presence
      of the surfactant and on the particle size, but is shown that the nanoparticle
      surfactant interface plays a dominant role. The size of the primary CoFe(2)O(4)
      particles is controlled by the type of salt, the synthesis temperature and the
      concentration of the precursors. A detailed characterization evidences the shape
      and size of the primary particles, the way in which the primary particles
      assemble and their features in terms of morphological, textural and magnetic
      properties.

PMID- 20045117
TI  - Evaluation of synaptophysin as an immunohistochemical marker for equine grass
      sickness.
AB  - It has been proposed that synaptophysin, an abundant integral membrane protein of
      synaptic vesicles, is an immunohistochemical marker for degenerating neurons in
      equine grass sickness (GS). In the present study, a statistically generated
      decision tree based on assessment of synaptophysin-immunolabelled ileal sections
      facilitated correct differentiation of all 20 cases of GS and 24 cases of non-GS
      disease (comprising eight horses with colic, six with neuroparalytic botulism and
      10 controls). This technique also facilitated correct diagnosis of GS in all
      three cases that had been erroneously classified as having non-GS disease based
      on conventional interpretation of haematoxylin and eosin-stained cryostat
      sections of ileal surgical biopsies. Further prospective studies involving larger
      numbers of horses are required to fully validate this decision tree. In contrast
      to GS, botulism did not alter ileal neuron density or synaptophysin labelling,
      indicating that different mechanisms cause neuronal damage and/or dysfunction in
      GS and botulism.

PMID- 20045118
TI  - A serotonin transporter gene polymorphism predicts peripartum depressive symptoms
      in an at-risk psychiatric cohort.
AB  - BACKGROUND: Peripartum major depressive disorder (MDD) is a prevalent psychiatric
      disorder with potential detrimental consequences for both mother and child.
      Despite its enormous health care relevance, data regarding genetic predictors of
      peripartum depression are sparse. The aim of this study was to investigate
      associations of the serotonin-transporter linked polymorphic region (5-HTTLPR)
      genotype with peripartum MDD in an at-risk population. METHODS: Two hundred and
      seventy four women with a prior history of MDD were genotyped for 5-HTTLPR and
      serially evaluated in late pregnancy (gestational weeks 31-40), early post-partum
      (week 1-8) and late post-partum (week 9-24) for diagnosis of a current major
      depressive episode (MDE) and depressive symptom severity. RESULTS: 5-HTTLPR S
      allele carrier status predicted the occurrence of a MDE in the early post-partum
      period only (OR=5.13, p=0.017). This association persisted despite continued
      antidepressant treatment. CONCLUSIONS: The 5-HTTLPR genotype may be a clinically
      relevant predictor of early post-partum depression in an at-risk population.
      OBJECTIVE: Peripartum major depressive disorder is a prevalent psychiatric
      disorder with potential detrimental consequences for both mother and child.
      Despite its enormous health care relevance, data regarding genetic predictors of
      peripartum depression are sparse. The aim of this study was to investigate
      associations of the serotonin-transporter linked polymorphic region (5-HTTLPR)
      genotype with peripartum MDD in an at-risk population.

PMID- 20045119
TI  - Excessive daytime somnolence in spinocerebellar ataxia type 1.
AB  - Autosomal dominant spinocerebellar ataxias (SCAs) are progressive
      neurodegenerative disorders which result in dysfunction of the neuronal systems
      of the spinal cord, brainstem, and cerebellum. The manifestations of daytime
      somnolence and abnormal sleep behavior have been described in SCA type 3 (SCA3)
      and SCA type 6 (SCA6), but as yet have not been described in SCA type 1 (SCA1).
      We report two cases of sleep disturbance, fatigue and excessive daytime
      somnolence in individuals with SCA1 and their progress through several therapies.
      These case studies are unique as they describe excessive daytime somnolence and
      sleep abnormalities in SCA1.

PMID- 20045120
TI  - Effects of electrical stimulation in vestibular cortex areas in humans.
AB  - The case of a patient with focal epilepsy is reported who underwent presurgical
      evaluation by stereotactic intracranial electroencephalographic (EEG) recording.
      A subdural semi-grid electrode, consisting of three multi-channel strip
      electrodes, was implanted over the temporal lobe and temporo-occipital region;
      one multi-channel depth electrode was applied towards the posterior insular
      cortex. During electrical stimulation and EEG monitoring eye movements were
      recorded by 3-D video-oculography. Stimulation of the medial temporal gyrus
      induced blurring of vision and horizontal nystagmus. Stimulation of the superior
      temporal gyrus with low intensities also induced blurring of vision and a similar
      nystagmus, whereas increased stimulus intensity elicited a nystagmus with
      horizontal, vertical, and torsional components. These findings support the
      hypothesis that the superior temporal gyrus is one of the regions of a
      multisensory network that plays a crucial role in the processing of vestibulo
      ocular information.

PMID- 20045121
TI  - Bilaterally symmetric cervical spondylotic amyotrophy: a novel presentation and
      review of the literature.
AB  - BACKGROUND: Cervical spondylotic amyotrophy (CSA) is considered a syndrome of (1)
      unilateral upper extremity weakness and atrophy, (2) affecting either the
      proximal or distal musculature, (3) without sensory impairment or lower extremity
      dysfunction. AIMS OF STUDY: The authors report a novel case of bilaterally
      symmetric CSA with blurring of the proximal-distal distinction, discuss the
      pathophysiology, and review the literature. METHODS: A 45 year old man presented
      with a several year history of insidiously progressive bilaterally symmetric
      upper extremity weakness and wasting, profound in the proximal musculature and
      moderate to severe in the distal muscle groups. RESULTS: Based on the clinical,
      neuroimaging and electrodiagnostic features, this patient harbors a more severe
      phenotype of the classical syndrome. CONCLUSION: The authors propose expanding
      the generally accepted definition of CSA to include this bilaterally symmetric
      form of disease, thereby minimizing diagnostic error or delay. Additionally,
      based on this case and a review of the literature, adherence to the proximal
      distal distinction should be avoided since it is commonly blurred. Accurate
      diagnosis is crucial since this presentation mimics the motor neuron disease
      variant Vulpian-Bernhardt syndrome. The importance of early diagnosis is
      underscored by reports of significant improvement with timely surgical
      decompression.

PMID- 20045123
TI  - [Recurrent pancreatitis in a human immunodeficiency virus-infected patient on
      antiretroviral therapy].

PMID- 20045122
TI  - High mercury levels in hair samples from residents of Taiji, a Japanese whaling
      town.
AB  - We investigated the mercury concentrations in red meat from pilot whales consumed
      by some residents of the Japanese whaling town, Taiji, and in hair samples from
      50 residents for their maker of mercury burden. The methyl mercury (M-Hg) level
      in the red meat was 5.9 microg/wet g, markedly higher than the US FDA action
      level and Cordex Alimentarius guideline level for predatory fish (1.0 microg/wet
      g). The average level of total mercury (T-Hg) in the hair from residents who ate
      whale meat more than once a month was 24.6 microg/g, whereas the average from the
      residents who did not consume any whale meat was 4.3 microg/g. The T-Hg
      concentrations in the hair from three donors exceeded 50 microg/g, the level for
      NOAEL set by WHO. The T-Hg level found in the Taiji whale meat consumers was
      markedly higher than that observed in the Japanese population overall (about 2
      microg/g).

PMID- 20045124
TI  - [Single lingual metastasis from a uterine leiomyosarcoma].

PMID- 20045125
TI  - [Chronic renal failure in type 2 diabetes patients].

PMID- 20045126
TI  - [Prevalence of use of hormone replacement therapy in women participating in a
      breast cancer screening program].
AB  - BACKGROUND AND OBJECTIVE: The purpose of the study was to determine the
      prevalence and type of hormone replacement therapy (HRT) in participants in a
      breast cancer screening program (BCSP) in Barcelona. PATIENTS AND METHOD:
      Prevalence of use of HRT was obtained through a survey. Information about type of
      HRT, gynecological history and socioeconomic and educational level was collected.
      Prevalence was calculated with its corresponding 95% confidence interval.
      RESULTS: From May 2001 to June 2005 there were 21835 participants in the BCSP
      with a mean age of 57,6 years. Most of the participants were postmenopausal
      (86,7%). Confirmed prevalence of use of HRT was 5,2%(CI95% 5,3-6,0) with a
      greater use among women aged 55 to 59 years. The most frequent types of HRT were
      tibolone (39,5%) followed by combined estrogens plus progestin (30,4%). Higher
      education was associated with a higher use of HRT. Neither the use or the type of
      HRT influenced the results of the screening program. CONCLUSIONS: Prevalence of
      use of HRT was 5,2% in this study. The most frequently used agents were tibolone
      and combined estrogens plus progestin.

PMID- 20045127
TI  - [Predictive factors for survival in idiopatic pulmonary fibrosis].

PMID- 20045128
TI  - [Severe hypomagnesaemia due to long-term treatment with omeprazole].

PMID- 20045129
TI  - [Hemophilic arthropathy].

PMID- 20045130
TI  - [Headache and blurred vision in a 26-year-old woman].

PMID- 20045131
TI  - [Acute mastoiditis and Lemierre's syndrome].

PMID- 20045132
TI  - [Diabetic ketoacidosis after switching insulin for exenatide].

PMID- 20045133
TI  - [Essential tremor is a neurodegenerative disease].

PMID- 20045134
TI  - [Growth hormone revisited].
AB  - Growth hormone (GH) is a pleiotropic hormone, expressed at pituitary and
      peripheral level, which plays a number of different roles far beyond of those
      classically described. Among these effects it is remarkable the neurotropic role
      of GH: the hormone increases the proliferation and survival of neural precursors
      in response to neurological injuries. At the cardiovascular level, GH improves
      the lipidic profile and decreases the factors of cardiac risk; the hormone
      recovers the endothelial function, improves the cardiac function and potentiates
      revascularisation in ischemic territories. Differently to that occurring with
      autocrine GH, exogenous GH administration does not seem to be related to
      oncogenesis. According to its effects, there are multiple potential clinical
      applications of GH: acute treatment of brain injury, due to its antiapoptotic
      effect; central or peripheral neural regeneration; acute treatment of perinatal
      anoxia, prevention cerebral palsy; revascularisation of ischemic areas; decrease
      of the time of bone consolidation after a bone fracture; and torpid ulcer
      healing.

PMID- 20045135
TI  - [New oral anticoagulants for the prevention of venous thromboembolism].

PMID- 20045137
TI  - [Post-colonoscopy spleen rupture].

PMID- 20045138
TI  - [Chronic lymphocytic leukemia].

PMID- 20045139
TI  - The influence of multiple indices of socioeconomic disadvantage across the adult
      life course on the metabolic syndrome: the Vietnam Experience Study.
AB  - Few studies have explored the relationship between individual and combined
      multiple indicators of socioeconomic status across the life course and the
      metabolic syndrome, or attempted to understand the mechanisms underlying any
      associations. The present study examined the associations between 4 indicators of
      socioeconomic status, individually and in combination, and metabolic syndrome
      risk in a study of male US veterans and examined the influence of health
      behaviors, intelligence, and psychologic distress on these associations.
      Participants (N = 4253) were drawn from the Vietnam Experience Study. From
      military service files, telephone interviews, and a medical examination,
      occupational, sociodemographic, health behavior, intelligence, psychologic, and
      health data were collected. The 4 indices of socioeconomic status were as
      follows: education achieved, early adulthood income, household income in midlife,
      and occupational prestige in midlife. Metabolic syndrome was diagnosed from the
      following: body mass index, fasting blood glucose or a diagnosis of diabetes,
      blood pressure-a diagnosis of hypertension or taking antihypertensives, high
      density lipoprotein cholesterol, and triglyceride levels. In models that adjusted
      for age, men in the lower 2 groups on the combined measure of socioeconomic
      status experienced a higher risk of metabolic syndrome. This association was
      accounted for mainly by education achieved, household income in midlife, and
      occupational prestige in midlife. Intelligence appeared to explain much of this
      association. Combined socioeconomic status measures across the life course were
      related to metabolic syndrome but in a threshold rather than dose-response
      manner. Intelligence appeared to mediate this relationship.

PMID- 20045140
TI  - Association of central adiposity with prediabetes and decreased insulin
      sensitivity in rural Chinese normal-weight and overweight women.
AB  - This study investigated whether high central adiposity was associated with
      prediabetes and decreased insulin sensitivity (IS) in both normal-weight (body
      mass index [BMI] <23 kg/m(2)) and overweight (BMI >or=23 kg/m(2)) rural Chinese
      women. Adipose variables measured by dual-energy x-ray absorptiometry (percentage
      body fat, percentage lower-body fat [%LF], and percentage trunk fat [%TF]) and
      general adipose variables (BMI and waist circumference) were used for examining
      the association of adiposity with prediabetes among 4071 rural Chinese women aged
      20 to 60 years. Furthermore, the association of adiposity with IS was tested in
      both normal- and overweight women with normal glucose tolerance. BMI was highly
      correlated with percentage body fat and waist circumference, but was weakly
      correlated with %LF and %TF. Both high %TF (top quartile of %TF) and low %LF
      (lower 3 quartiles of %LF) were associated with higher prevalence of prediabetes
      in both normal- and overweight women. Compared with normal-weight women in low
      %TF, the odds of prediabetes were similarly increased for women with high %TF
      regardless of whether they were overweight (odds ratio [95% confidence interval]
      = 1.6 [1.3-2.0]) or not (odds ratio [95% confidence interval] = 1.5 [1.2-2.0]).
      Similarly, among 3280 women with normal glucose tolerance, high %TF was
      associated with increased fasting insulin, 2-hour oral glucose tolerance test
      insulin, and homeostasis model assessment of insulin resistance regardless of
      weight status (normal or overweight). Among relatively lean, rural Chinese women,
      high %TF was associated with increased odds of prediabetes and lower IS
      regardless of weight status (normal or overweight).

PMID- 20045141
TI  - Methionine restriction effects on mitochondrial biogenesis and aerobic capacity
      in white adipose tissue, liver, and skeletal muscle of F344 rats.
AB  - Methionine restriction increases life span in rats and mice and reduces age
      related accretion of adipose tissue in Fischer 344 rats. Recent reports have
      shown that adipose tissue mitochondrial content and function are associated with
      adiposity; therefore, the expression of genes involved in mitochondrial
      biogenesis and oxidative capacity was examined in white adipose tissue, liver,
      and skeletal muscle from Fischer 344 rats fed control (0.86% methionine) or
      methionine-restricted (0.17% methionine) diets for 3 months. Methionine
      restriction induced transcriptional changes of peroxisome proliferator-activated
      receptors, peroxisome proliferator-activated receptor coactivators 1alpha and
      1beta, and some of their known target genes in all of these tissues. In addition,
      tissue-specific responses were elicited at the protein level. In inguinal adipose
      tissue, methionine restriction increased protein levels of peroxisome
      proliferator-activated receptor and peroxisome proliferator-activated receptor
      coactivator target genes. It also induced mitochondrial DNA copy number,
      suggesting mitochondrial biogenesis and corresponding with the up-regulation of
      citrate synthase activity. In contrast, methionine restriction induced changes in
      mitochondrial glycerol-3-phosphate dehydrogenase activity and stearoyl-coenzyme A
      desaturase 1 protein levels only in liver and uncoupling protein 3 and cytochrome
      c oxidase subunit IV protein levels only in skeletal muscle. No increase in
      mitochondrial DNA copy number was observed in liver and skeletal muscle despite
      an increase in mitochondrial citrate synthase activity. The results indicate that
      adiposity resistance in methionine-restricted rats is associated with
      mitochondrial biogenesis in inguinal adipose tissue and increased mitochondrial
      aerobic capacity in liver and skeletal muscle.

PMID- 20045142
TI  - Common polymorphisms of the peroxisome proliferator-activated receptor-gamma
      (Pro12Ala) and peroxisome proliferator-activated receptor-gamma coactivator-1
      (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2
      diabetes mellitus.
AB  - We investigated the effects of the common polymorphisms in the peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma
      coactivator-1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese
      with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes
      mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change
      in previous medications. All patients were genotyped for the PPAR-gamma Pro12Ala
      and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs
      13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more
      frequent in pioglitazone responders than in nonresponders. The distribution of
      PGC-1 genotypes and alleles was not significantly different between responders
      and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3 +/-
      51.7 mg/dL, P < .001) and hemoglobin A(1c) (0.57% +/- 1.44% vs 0.35% +/- 1.10%, P
      = .004) levels was significantly greater in subjects with the Ala12 carriers
      (Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline
      fasting glucose and triglyceride levels were related to the response of
      pioglitazone. Only the PPAR-gamma Pro12Ala polymorphism was found to be
      associated with the response of pioglitazone by multiple logistic regression
      analysis. The PPAR-gamma Pro12Ala gene polymorphism is associated with the
      response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These
      findings may be helpful for targeted treatment of diabetes by identifying
      patients who are likely to respond to pioglitazone.

PMID- 20045143
TI  - Poor prediction of resting energy expenditure in obese women by established
      equations.
AB  - The objective of the study was to evaluate the accuracy of established prediction
      equations that calculate resting energy expenditure (REE) in obese women. This
      was a cross-sectional study. In 273 mildly to severely obese women (age, 41.7 +/-
      13.2 years; body mass index, 42.8 +/- 7.0 kg/m(2)), REE was measured by indirect
      calorimetry (mREE), along with fat mass (FM) and fat-free mass (FFM) by
      bioelectrical impedance analysis. Eleven established equations were used to
      predict REE (pREE), with 9 equations basing on the anthropometric parameters body
      weight and height and 2 equations including body composition parameters (FM,
      FFM). All equations provided pREE values that significantly correlated with mREE
      (r > 0.66, P < .001), although 8 equations systematically underestimated mREE (P
      < .05). Of note, even the best equation was not able to accurately predict mREE
      with a deviation of less than +/-10% in more than 70% of the tested women.
      Furthermore, equations using body composition data were not superior in
      predicting REE as compared with equations exclusively including anthropometric
      variables. Multiple linear regression analyses revealed 2 new equations--one
      including body weight and age and another including FM, FFM, and age--that
      explained 56.9% and 57.2%, respectively, of variance in mREE. However, when these
      2 new equations were applied to an independent sample of 33 obese women, they
      also provided an accurate prediction (+/-10%) of mREE in only 56.7% and 60.6%,
      respectively, of the women. Data show that an accurate prediction of REE is not
      feasible using established equations in obese women. Equations that include body
      composition parameters as assessed by bioelectrical impedance analysis do not
      increase the accuracy of prediction. Based on our results, we conclude that
      calculating REE by standard prediction equations does not represent a reliable
      alternative to indirect calorimetry for the assessment of REE in obese women.

PMID- 20045144
TI  - Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism.
AB  - Tissue availability of polyunsaturated fatty acids (PUFAs) depends on dietary
      intake and metabolic turnover and has a major impact on human health. Strong
      associations between variants in the human genes fatty acid desaturase 1 (FADS1,
      encoding Delta-5 desaturase) and fatty acid desaturase 2 (FADS2, encoding Delta-6
      desaturase) and blood levels of PUFAs and long-chain PUFAs (LC-PUFAs) have been
      reported. The most significant associations and the highest proportion of
      genetically explained variability (28%) were found for arachidonic acid (20:4n
      6), the main precursor of eicosanoids. Subjects carrying the minor alleles of
      several single nucleotide polymorphisms had a lower prevalence of allergic
      rhinitis and atopic eczema. Therefore, blood levels of PUFAs and LC-PUFAs are
      influenced not only by diet, but to a large extent also by genetic variants
      common in a European population. These findings have been replicated in
      independent populations. Depending on genetic variants, requirements of dietary
      PUFA or LC-PUFA intakes to achieve comparable biological effects may differ. We
      recommend including analyses of FADS1 and FADS2 polymorphism in future cohort and
      intervention studies addressing biological effects of PUFAs and LC-PUFAs.

PMID- 20045145
TI  - Preliminary report: circulating levels of the adipokine vaspin in gestational
      diabetes mellitus and preeclampsia.
AB  - The objective of the study was to investigate serum levels of the insulin
      sensitizing adipokine vaspin in patients with gestational diabetes mellitus (GDM)
      and preeclampsia (PE) as compared with healthy controls of similar gestational
      age. Vaspin serum levels were quantified by enzyme-linked immunosorbent assay in
      control (n = 102), GDM (n = 40), and PE (n = 22) subjects. Median maternal vaspin
      concentrations were not significantly different in GDM, PE, and control subjects.
      Furthermore, vaspin did not significantly correlate to clinical and biochemical
      measures of renal function, glucose, and lipid metabolism, as well as
      inflammation. Circulating vaspin levels are not significantly different between
      GDM, PE, and control subjects and do not correlate with insulin sensitivity in
      pregnant subjects.

PMID- 20045146
TI  - Effects of acute ethionine injection on plasma ghrelin and obestatin levels in
      trained male rats.
AB  - Ghrelin and obestatin are orexigenic and anorexigenic peptides, respectively,
      that are secreted from the stomach mucosa into the circulation. These peptides
      have opposing actions on food intake, weight gain, and adiposity. It is thought
      that ghrelin is sensitive to a negative energy environment and also plays a
      considerable role in short- and long-term energy balance and glucose homeostasis.
      It has been suggested that the levels of ghrelin and obestatin are upregulated by
      fasting, hypoglycemic status, and a physical-exercise-induced energy deficit.
      Ethionine (ETH), the ethyl analogue of methionine, has been shown to increase
      food intake, decrease adenosine triphosphate (ATP) and glycogen levels, and
      inhibit protein synthesis in the liver. The purpose of this study was to examine
      the effect of a single dose of ETH (0.7 mg/g of body weight) injection on resting
      plasma total ghrelin and obestatin concentrations in male trained rats. Thirty
      two adult Wistar male rats weighing 180 to 200 g were randomly assigned to
      control (n = 16) and training (n =16) groups. The training group was exercised
      for 10 weeks (25 m/min, 0% grade, 60 minutes, and 5 d/wk). Seventy-two hours
      after the last exercise session, rats were injected with either saline (NaCl) or
      ETH and then killed. Ethionine compared with a NaCl injection resulted in
      significant (P < .013) reductions in resting hepatic ATP and glycogen levels, and
      in a significant (P < .001) increase in concentrations of plasma total ghrelin
      but not obestatin. The results indicate that ETH-induced liver ATP and glycogen
      deficiency could exert a powerful regulatory influence on plasma total ghrelin,
      but this is not the case for obestatin. Findings demonstrate the short-term
      energy-regulating capacity of ghrelin.

PMID- 20045147
TI  - Endogenous red blood cell membrane fatty acids and sudden cardiac arrest.
AB  - Little is known of the associations of endogenous fatty acids with sudden cardiac
      arrest (SCA). We investigated the associations of SCA with red blood cell
      membrane fatty acids that are end products of de novo fatty acid synthesis:
      myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16:1 n7), vaccenic
      acid (18:1 n7), stearic acid (18:0), oleic acid (18:1 n9), and a related fatty
      acid, cis-7 hexadecenoic acid (16:1 n9). We used data from a population-based
      case-control study where cases, aged 25 to 74 years, were out-of-hospital SCA
      patients attended by paramedics in Seattle, WA (n = 265). Controls, matched to
      cases by age, sex, and calendar year, were randomly identified from the community
      (n = 415). All participants were free of prior clinically diagnosed heart
      disease. We observed associations of higher red blood cell membrane levels of
      16:0, 16:1n-7, 18:1n-7, and 16:1n-9 with higher risk of SCA. In analyses adjusted
      for traditional SCA risk factors and trans- and n-3 fatty acids, a 1-SD-higher
      level of 16:0 was associated with 38% higher risk of SCA (odds ratio, 1.38; 95%
      confidence interval, 1.12-1.70) and a 1-SD-higher level of 16:1n-9 with 88%
      higher risk (odds ratio, 1.88; 95% confidence interval, 1.27-2.78). Several fatty
      acids that are end products of fatty acid synthesis are associated with SCA risk.
      Further work is needed to investigate if conditions that favor de novo fatty acid
      synthesis, such as high-carbohydrate/low-fat diets, might also increase the risk
      of SCA.

PMID- 20045149
TI  - Glucose-transporter-mediated positive inotropic effects in human myocardium of
      diabetic and nondiabetic patients.
AB  - Insulin causes inotropic effects via Ca(2+)-dependent and Ca(2+)-independent
      pathways. The latter one is potentially glucose dependent. We examined inotropic
      responses and signal transduction of insulin in human atrial myocardium of
      diabetic and nondiabetic patients to test for the role of glucose transporters.
      Experiments were performed in isolated atrial myocardium of 88 patients
      undergoing cardiac surgery and 28 ventricular muscle samples of explanted hearts.
      Influence of insulin (0.02 micromol/L) on isometric twitch force was examined
      with and without blocking glucose transporter (GLUT) 4 translocation
      (latrunculin), sodium-coupled glucose transporter (SGLT) 1 (phlorizin, T-1095A),
      or PI3-kinase (wortmannin). Experiments were performed in Tyrode solution
      containing glucose or pyruvate as energetic substrate. Messenger RNA expression
      of glucose transporters (GLUT1, GLUT4, SGLT1, SGLT2) was analyzed in atrial and
      ventricular myocardium of both diabetic and nondiabetic patients. Developed force
      increases after insulin (to 117.8% +/- 2.4% and 115.8% +/- 1.9%) in trabeculae
      from patients with and without diabetes. Inotropic effect was reduced after
      displacing glucose with pyruvate as well as after PI3-kinase inhibition (to 103%
      +/- 2%) or inhibition of glucose transporters GLUT4 (to 105% +/- 2%) and SGLT1
      (phlorizin to 106% +/- 2%, T-1095A to 105% +/- 2%), without differences between
      the 2 groups. In glucose-free pyruvate-containing solution, only inhibition of
      PI3-kinase but not blocking glucose transporters resulted in further inhibitory
      effects. Messenger RNA expression did not show significant differences between
      patients with or without diabetes. Insulin exerts positive inotropic effects in
      human atrial myocardium. These effects are mediated via a PI3-kinase-sensitive
      and a glucose-transport-sensitive pathway. Differences in functional effects or
      messenger RNA expression of glucose transporters were not detectable between
      patients with and without diabetes.

PMID- 20045150
TI  - Adipose tissue lamin A/C messenger RNA expression in women.
AB  - Mutations in the lamin A/C gene (LMNA) cause lipodystrophy. However, little data
      are available on lamin A/C expression in various fat depots in women. We
      recruited 34 women scheduled for gynecologic surgery. Blood samples were
      collected on the morning of surgery to obtain a detailed lipid profile.
      Radiological examinations were performed to measure total body fat mass and
      abdominal fat accumulation. Fat samples were taken from the subcutaneous (SC) fat
      depot and from the greater omentum (OM) during the surgical procedure. Whole
      adipose tissue samples were used for total messenger RNA (mRNA) extraction and
      real-time polymerase chain reaction quantification of the LMNA transcript. No
      association was observed between lamin A/C mRNA expression, either in SC or OM
      fat tissue, and adiposity measures. Women with low SC lamin A/C expression,
      identified on the basis of the median value of SC lamin A/C mRNA expression, had
      a significantly altered lipid profile including lower levels of high-density
      lipoprotein (HDL) cholesterol and HDL(2) cholesterol and reduced HDL(2)
      cholesterol to HDL(3) cholesterol ratio (P < .05 for all). These women were also
      characterized by higher cholesterol to HDL cholesterol, low-density lipoprotein
      triglycerides, very low-density lipoprotein-apolipoprotein B, and low-density
      lipoprotein cholesterol to HDL cholesterol (P < .05 for all). Low SC lamin A/C
      mRNA expression levels were also associated with significantly increased
      lipolysis in isolated fat cells from this fat depot. Specifically, the response
      to lipolytic agent isoproterenol was significantly increased at doses ranging
      from 10(-5) to 10(-10) mol/L (P < .05). A similar trend was observed in OM fat
      cells but did not reach significance. In conclusion, low lamin A/C expression in
      SC adipose tissue is associated with significant alterations in the lipid profile
      and increased fat cell lipolysis, independent of the level of total or abdominal
      adiposity.

PMID- 20045148
TI  - The characterization of Abelson helper integration site-1 in skeletal muscle and
      its links to the metabolic syndrome.
AB  - The human Abelson helper integration site-1 (AHI1) gene is associated with both
      neurologic and hematologic disorders; however, it is also located in a
      chromosomal region linked to metabolic syndrome phenotypes and was identified as
      a type 2 diabetes mellitus susceptibility gene from a genomewide association
      study. To further define a possible role in type 2 diabetes mellitus development,
      AHI1 messenger RNA expression levels were investigated in a range of tissues and
      found to be highly expressed in skeletal muscle as well as displaying elevated
      levels in brain regions and gonad tissues. Further analysis in a rodent polygenic
      animal model of obesity and type 2 diabetes mellitus identified increased Ahi-1
      messenger RNA levels in red gastrocnemius muscle from fasted impaired glucose
      tolerant and diabetic rodents compared with healthy animals (P < .002). Moreover,
      elevated gene expression levels were confirmed in skeletal muscle from fasted
      obese and type 2 diabetes mellitus human subjects (P < .02). RNAi-mediated
      suppression of Ahi-1 resulted in increased glucose transport in rat L6 myotubes
      in both the basal and insulin-stimulated states (P < .01). Finally, single
      nucleotide polymorphism association studies identified 2 novel AHI1 genetic
      variants linked with fasting blood glucose levels in Mexican American subjects (P
      < .037). These findings indicate a novel role for AHI1 in skeletal muscle and
      identify additional genetic links with metabolic syndrome phenotypes suggesting
      an involvement of AHI1 in the maintenance of glucose homeostasis and type 2
      diabetes mellitus progression.

PMID- 20045151
TI  - Effects of a 6-month lifestyle modification intervention on the cardiometabolic
      risk factors and health-related qualities of life in women with metabolic
      syndrome.
AB  - Although therapeutic lifestyle modification (TLM) has been recommended as a
      cornerstone treatment of metabolic syndrome (MetS), little is known about the
      biobehavioral effects of a TLM program for patients in a community. The purpose
      of this study was to examine the effects of a 6-month TLM program on MetS risk
      factors and health-related qualities of life (HRQOL) among middle-aged and older
      women in a community in Korea. Fifty-two women (mean age, 62.7 +/- 9.0 years)
      with MetS were recruited from 3 community health centers and were randomly
      assigned to the intervention (n = 31) or control (n = 21) groups. The patients in
      the intervention group participated in supervised TLM sessions for 6 months. The
      TLM program included health monitoring, counseling, health education, exercise,
      and dieting. Metabolic risk factors and HRQOL were measured at baseline, during
      the study (month 3), at completion (month 6), and post completion (month 12) of
      the TLM program. Compared with the control group, the TLM group showed
      significantly greater reductions in body weight (P < .001) and waist
      circumference (P < .001); these effects were sustained for 6 months after
      intervention. With regard to HRQOL, the TLM group showed greater improvements in
      physical function (P = .017), general health (P < .001), vitality (P = .008), and
      mental health (P = .027). These improvements, however, were not sustained after
      the intervention. The results indicate that a nurse-led systematic TLM program
      may be an effective strategy for managing middle-aged and older women with MetS
      at a community level.

PMID- 20045152
TI  - Age-dependent associations of smoking and drinking with non-high-density
      lipoprotein cholesterol.
AB  - Serum high-density lipoprotein (HDL) cholesterol levels are influenced by
      habitual smoking and drinking. Non-HDL cholesterol is known to be a potent
      predictor of cardiovascular disease. However, it remains to be determined whether
      the associations of non-HDL cholesterol with smoking and drinking differ with
      age. The objectives of this study were to investigate relationships among
      smoking, drinking, and non-HDL cholesterol and to investigate interactions of age
      with smoking and drinking regarding serum non-HDL cholesterol levels. Subjects
      (54,020 Japanese men aged 20-69 years) were divided into drinkers and nondrinkers
      or into smokers and nonsmokers and were further divided into 5 age groups with 10
      year intervals. Subjects in each age group were divided into 3 subgroups
      according to alcohol or cigarette consumption. The mean levels of serum non-HDL
      cholesterol calculated after adjustment for age and body mass index were compared
      among the groups. In nondrinkers, non-HDL cholesterol levels of subjects in their
      40s or older were significantly higher in heavy smokers than in nonsmokers,
      whereas non-HDL cholesterol levels of subjects in their 20s and 30s were not
      significantly different among non-, light, and heavy smokers. In drinkers, non
      HDL cholesterol levels of subjects in all age groups were not higher in light and
      heavy smokers than in nonsmokers. In nonsmokers, non-HDL cholesterol in subjects
      in their 30s or older was significantly lower in light and heavy drinkers than in
      nondrinkers, whereas this difference was not observed in subjects in their 20s.
      In smokers, non-HDL cholesterol levels of subjects in all age groups were
      significantly lower in light and heavy drinkers than in nondrinkers, and the
      differences in non-HDL cholesterol between drinkers and nondrinkers tended to
      increase with advance of age. The difference in non-HDL cholesterol between
      drinkers and nondrinkers tended to be greater in smokers than in nonsmokers.
      Thus, the associations of non-HDL cholesterol with smoking and drinking were
      modified by drinking and smoking, respectively. Smoking is associated with high
      non-HDL cholesterol in nondrinkers, and drinking is associated with low non-HDL
      cholesterol in nonsmokers; these associations are shown at middle and elderly
      ages but not at young ages.

PMID- 20045153
TI  - Plasma apelin levels in subjects with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD), one of the most common forms of chronic
      liver disease, is closely associated with obesity and insulin resistance. Recent
      studies suggest that apelin, a newly described adipokine, is associated with
      hyperinsulinemia and inflammation. The aim of the study was to investigate plasma
      apelin concentrations in biopsy-proven NAFLD patients who had no metabolic
      confounders and also to search for the association of apelin with adiponectin,
      body mass index (BMI), and insulin sensitivity. Fifty male patients with NAFLD
      and 30 healthy male controls were enrolled. Apelin was measured along with BMI,
      lipids, glucose, insulin, adiponectin, and homeostasis model assessment (HOMA) of
      insulin resistance indexes. Plasma apelin levels were significantly higher and
      adiponectin levels were lower in NAFLD patients when compared with the controls
      (P < .001 and P = .013, respectively). In multivariate analysis adjusted for BMI
      and HOMA indexes, the differences in apelin and adiponectin disappeared in the 2
      groups (P = .3 and P = .1, respectively). In addition, apelin levels were
      positively correlated with BMI (r = 0.29, P = .05) and HOMA indexes (r = 0.4, P =
      .008) in subjects with NAFLD. The results of this preliminary study suggest that
      plasma apelin levels are not altered in nondiabetic and normotensive male
      subjects with NAFLD.

PMID- 20045154
TI  - Diet-genotype interactions in the early development of obesity and insulin
      resistance in mice with a genetic deficiency in tumor necrosis factor-alpha.
AB  - The onset of insulin resistance, the sites of action, and the mechanisms through
      which tumor necrosis factor-alpha (TNF-alpha) exacerbates the increase in
      adiposity and the development of insulin resistance in mice fed high-fat (HF)
      diet remain unclear. Here we investigated the effect of TNF-alpha deficiency on
      adiposity and insulin resistance during the initial 1 to 4 weeks of HF feeding.
      We examined body weight; the distribution of white adipose tissue (WAT);
      homeostasis model assessment; and levels of leptin, resistin, and adiponectin in
      the initial 4 weeks of HF feeding in TNF-alpha knockout (KO) mice and wild-type
      (WT) controls. Through 4 weeks of HF feeding, KO mice, unlike WT mice, maintained
      normal insulin sensitivity. Although WT-HF and KO-HF mice had similar levels of
      WAT at this time, KO-HF mice had more subcutaneous and less epididymal fat than
      WT-HF mice. The KO-HF mice also had less liver fat than the WT-HF mice. Finally,
      KO-HF mice had lower plasma levels of resistin than WT-HF mice. These data
      demonstrate that genetic lack of TNF-alpha protects insulin sensitivity during
      the early phase of HF feeding in the absence of altered total WAT. The data also
      suggest that the mechanism maintaining insulin sensitivity in the absence of TNF
      alpha may involve redirection of the fat deposition to the metabolically more
      inert subcutaneous depot or decreases in circulating resistin and resultant
      decrease in liver fat deposition. The efficacy of therapeutic measures designed
      to counteract the effects of TNF-alpha may be increased during the early stages
      of obesity and insulin resistance.

PMID- 20045155
TI  - The cortisol awakening response and the metabolic syndrome in a population-based
      sample of middle-aged men and women.
AB  - The objective was to explore the relationship between the cortisol awakening
      response (CAR) and the metabolic syndrome (MetS) as defined by the National
      Cholesterol Education Program criteria. The final study sample consisted of 91
      women (14 with MetS) and 84 men (15 with MetS), aged 45 to 70 years, from a
      general population sample. The only exclusion criteria were no consent,
      pregnancy, or insufficient cortisol testing. On the day of measurement (weekday),
      salivary cortisol was sampled at awakening and 15 minutes after awakening.
      Relative CAR (CAR%) and the MetS were the main variables studied. Results showed
      that, in women with the MetS, cortisol at awakening was significantly lower
      (mean, 8.92 vs 12.33 nmol/L; P = .05) and the CAR was significantly higher (91.4%
      vs 36.5%, P < .001) than in women without the syndrome. Significant difference in
      the relative CAR was also present between men and women with MetS (38.5% and
      91.4%, respectively; P = .02). No difference was seen in the awakening response
      comparing men with and without the MetS. In a regression model, the response to
      awakening was dependent on the MetS in women (F(1,89) = 13.19, P < .001); but the
      model was not significant in men. Furthermore, the awakening response was
      associated with more depressive symptoms in women (F(1,80) = 8.12, P = .01) and
      with weekday/weekend cortisol sampling in men (F(1,82) = 4.63, P = .03). The
      association between the relative CAR and the MetS remained significant but
      somewhat attenuated after adjusting for depressive symptoms (P = .01). Results
      indicate a sex difference in the CAR% in the presence of the MetS independent of
      depressive symptoms, a known correlate of the MetS.

PMID- 20045156
TI  - Common INSIG2 polymorphisms are associated with age-related changes in body size
      and high-density lipoprotein cholesterol from young adulthood to middle age.
AB  - Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of
      cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10
      kilobases upstream of the INSIG2 gene, was identified in a genomewide association
      study of obesity. We conducted an association study of 12 INSIG2 tag-single
      nucleotide polymorphisms with longitudinal measures of body size (body mass index
      and waist circumference) and lipid metabolism (plasma high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We
      investigated their interaction with age in 4304 Coronary Artery Risk Development
      in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively
      for 20 years. rs7566605 was not associated with variation in body size or lipid
      metabolism at any age in either racial group. However, rs1352083 and rs10185316
      were associated with age-related decline in high-density lipoprotein cholesterol
      in whites (P = .0005 and .04, respectively). A similar trend was observed in
      blacks who consistently maintained a body mass index less than 25 kg/m(2) over
      the study period. These data support a role of INSIG2 sequence variation in the
      regulation of cholesterol metabolism.

PMID- 20045157
TI  - l-Carnitine l-tartrate supplementation favorably affects biochemical markers of
      recovery from physical exertion in middle-aged men and women.
AB  - The purpose of this study was to examine the effects of Carnipure tartrate
      (Lonza, Allendale, NJ) supplementation (total dose of 2 g/d of l-carnitine) on
      markers of performance and recovery from physical exertion in middle-aged men and
      women. Normally active and healthy men (n = 9, 45.4 +/- 5.3 years old) and women
      (n = 9, 51.9 +/- 5.0 years old) volunteered to participate in the investigation.
      Double-blind, placebo, balanced treatment presentation and crossover design were
      used with 3 weeks and 3 days of supplementation followed by a 1-week washout
      period before the other counterbalanced treatment was initiated. After 3 weeks of
      each supplementation protocol, each participant then performed an acute
      resistance exercise challenge of 4 sets of 15 repetitions of squat/leg press at
      50% 1-repetition maximum and continued supplementation over the recovery period
      that was evaluated. Blood samples were obtained at preexercise and at 0, 15, 30,
      and 120 minutes postexercise during the acute resistance exercise challenge and
      during 4 recovery days as well. Two grams of l-carnitine supplementation had
      positive effects and significantly (P < or = .05) attenuated biochemical markers
      of purine metabolism (ie, hypoxanthine, xanthine oxidase), free radical formation
      (malondialdehyde), muscle tissue disruption (myoglobin, creatine kinase), and
      muscle soreness after physical exertion. However, markers of physical performance
      (ie, strength, power, get up and go) were not affected by supplementation. These
      findings support our previous findings of l-carnitine in younger people that such
      supplementation can reduce chemical damage to tissues after exercise and optimize
      the processes of muscle tissue repair and remodeling.

PMID- 20045158
TI  - [Minimally invasive surgery for Chance fractures: Three case studies].
AB  - BACKGROUND AND PURPOSE: Chance fractures are quite rare injuries that require
      surgical treatment in cases of spinal instability. Development of percutaneous
      and minimally invasive procedures can alter the management of such lesions,
      resulting in fewer related soft tissue lesions and morbidities. METHODS: We
      present our experience with three patients who underwent percutaneous posterior
      osteosynthesis associated with a minimally invasive anterior graft for discal
      lesion. The first two cases presented fracture through the disc and
      osteosynthesis was done on a single mobile level. In the third case with a bony
      Chance fracture, we performed a short-segment fixation one level above and below
      the fractured vertebra. RESULTS: In all three cases, operative blood loss was
      minimal and clinical outcomes were favorable, with tolerable postoperative pain.
      Fusion and consolidation were visible for all the patients without loss of
      correction or implant failure. CONCLUSION: Percutaneous osteosynthesis and
      minimally invasive surgery can be an advantageous alternative for the management
      of Chance fractures. They allow early mobilization of the patient with less soft
      tissue trauma and morbidities associated with open procedures.

PMID- 20045159
TI  - [Second surgery for glioblastoma. A 4-year retrospective study conducted in both
      the Montpellier and Nice Departments of Neurosurgery. A literature review].
AB  - BACKGROUND AND PURPOSE: Glioblastoma, the most common malignant primary brain
      tumor in adults, is usually rapidly fatal. The current care standards for newly
      diagnosed glioblastoma consist, when feasible, in surgical resection,
      radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite
      optimal treatment, nearly all malignant gliomas recur. If the tumor is
      symptomatic for mass effect, repeated surgery may be proposed. METHODS: We
      retrospectively analyzed the survival of patients with histologically confirmed
      primary glioblastoma (WHO grade 4) who were operated in two centers between
      January 2004 and December 2007. All patients who underwent a second resection for
      recurrent glioblastoma were included. RESULTS: During this period, 320 patients
      were operated in the two centers, with 240 surgical resections and 80 surgical
      biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second
      surgical resection for glioblastoma. The mean age was 52 years. At the end of the
      study, seven patients were alive. The median survival was 24 months and
      progression-free survival was 7.5 months. CONCLUSIONS: The effect of resection of
      recurrent glioblastoma on survival has not been extensively studied. No
      randomized trials have been conducted. Our data were globally identical to other
      retrospective studies. Selected patients with recurrent glioblastoma may be
      candidates for repeated surgery when the situation appears favorable based on
      assessment of the individual patient's factors. Factors such medical history,
      neurological status, location of the tumor, and progression-free survival have
      been proven in retrospective studies to give better results.

PMID- 20045160
TI  - Hemangioblastoma of the corpus callosum: A case report and review of the
      literature on its origin.
AB  - A third case of corpus callosum hemangioblastoma (HB) is presented. With no
      preoperative embolization, surgery was uneventful and the postoperative course
      was excellent. Based on the literature, we attempted to clarify the histogenesis
      of HB and to explain why they are exceptional in the supratentorial region in
      contrast to the posterior cranial fossa. The VHL gene is expressed particularly
      in Purkinje cells of the cerebellum, but this expression is also possible in
      supratentorial structures. Its mutation leads to developmental arrest of
      angioblasts that become potentially neoplastic cells. These CD133-positive
      pluripotent neoplastic angioblasts, similar to stem cells, may be immature HB in
      the brain. They also express VEGF, coexpress Epo/EpoR, and are capable of
      differentiation into primitive vascular structures. This coexpression may not
      only mediate developmental stagnation, but may also induce HB proliferation.
      Therefore, HB tumorigenesis may be initiated during embryogenesis and may
      originate from angiomesenchyma because of the expression of three cell types
      (stromal cells, pericytes, and endothelial cells) in vimentin. Their capacity for
      proliferation and differentiation in HB depends on the microenvironment.

PMID- 20045161
TI  - [Atypical Lewy body disease revealed by burning mouth syndrome and a pseudo
      psychiatric syndrome].
AB  - INTRODUCTION: Among the degenerative diseases of the nervous system, Lewy body
      disease has the most psychiatric symptoms especially hallucinations, delusion and
      identification disorders. CASE REPORT: We report a case of Lewy body disease that
      started with a burning mouth syndrome for three year as the only symptom before
      the development of a pseudo-psychiatric syndrome (melancholy and Capgras). None
      of the usual cardinal criteria were present. MRI, cerebrospinal fluid, and DAT
      scan findings enabled the diagnosis. CONCLUSION: The dopaminergic hypothesis put
      forward in some cases of burning mouth syndrome might explain this symptom in
      Lewy body disease.

PMID- 20045162
TI  - A comparison of laparoscopic and robotic assisted suturing performance by experts
      and novices.
AB  - BACKGROUND: Surgical robotics has been promoted as an enabling technology. This
      study tests the hypothesis that use of the robotic surgical system can
      significantly improve technical ability by comparing the performance of both
      experts and novices on a complex laparoscopic task and a robotically assisted
      task. METHODS: Laparoscopic experts (LE) with substantial laparoscopic and
      robotic experience (n = 9) and laparoscopic novices (LN) (n = 20) without any
      robotic experience performed sequentially 10 trials of a suturing task using
      either robotic or standard laparoscopic instrumentation fitted to the ProMIS
      surgical simulator. Objective performance metrics provided by ProMIS (total task
      time, instrument pathlength, and smoothness) and an assessment of learning curves
      were analyzed. RESULTS: Compared with LNs, the LEs demonstrated significantly
      better performance on all assessment measures. Within the LE group, there was no
      difference in smoothness (328 +/- 159 vs 355 +/- 174; P = .09) between robot
      assisted and standard laparoscopic tasks. An improvement was noted in total task
      time (113 +/- 41 vs 132 +/- 55 sec; P < .05) and instrument pathlengths (371 +/-
      163 vs 645 +/- 269 cm; P < .05) when using the robot. This advantage in terms of
      total task time, however, was lost among the LEs by the last 3 trials (114 +/- 40
      vs 118 +/- 49 s; P = .84), while instrument pathlength remained better
      consistently throughout all the trials. For the LNs, performance was
      significantly better in the robotic trials on all 3 measures throughout all the
      trials. CONCLUSION: The ProMIS surgical simulator was able to distinguish between
      skill levels (expert versus novice) on robotic suturing tasks, suggesting that
      the ProMIS is a valid tool for measuring skill in robot-assisted surgery. For all
      the ProMIS metrics, novices demonstrated consistently better performance on a
      suturing task using robotics as compared to a standard laparoscopic setup. This
      effect was less evident for experts who demonstrated improvements only in their
      economy of movement (pathlength), but not in the speed or smoothness of
      performance. Robotics eliminated the early learning curve for novices, which was
      present when they used standard laparoscopic tools. Overall, this study suggests
      that, when performing complex tasks such as knot tying, surgical robotics is most
      useful for inexperienced laparoscopists who experience an early and persistent
      enabling effect. For experts, robotics is most useful for improving economy of
      motion, which may have implications for the highly complex procedures in limited
      workspaces (eg, prostatectomy).

PMID- 20045163
TI  - Clinicopathologic significance of leptin and leptin receptor expressions in
      papillary thyroid carcinoma.
AB  - BACKGROUND: Epidemiologic studies have shown that obesity is associated with an
      increased risk of thyroid cancer. Leptin, an adipocyte-derived cytokine, can act
      as a growth factor on certain normal and transformed cells. Aberrant expression
      of leptin or leptin receptor has been detected in some types of cancer. The aim
      of this study is to determine immunohistochemical expression of leptin and leptin
      receptor in papillary thyroid cancer to investigate the relationship between
      their expression and clinicopathologic features. METHODS: The expression of
      leptin and leptin receptor was assessed in 49 primary neoplasms and 15 lymph node
      metastases using a semiquantitative immunohistochemical staining method. RESULTS:
      Leptin and leptin receptor were expressed in 37% and 51% of papillary thyroid
      cancer, respectively. They were not expressed in normal follicles. In the primary
      neoplasms and the metastatic nodes, expression of leptin correlated closely with
      leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal
      metastases). Expression of either protein was associated with greater neoplasm
      size (leptin expression, 32.0 +/- 10.7 vs 20.5 +/- 8.4 mm; P = .001; leptin
      receptor expression, 27.9 +/- 11.5 vs 21.4 +/- 9.0 mm; P = .032). Coexpression of
      leptin and leptin receptor in primary neoplasms had greater incidence of lymph
      node metastasis (P = .038). CONCLUSION: Expression of leptin and/or leptin
      receptor in papillary thyroid cancer is associated with neoplasm aggressiveness,
      including tumor size and lymph node metastasis.

PMID- 20045164
TI  - Taiwan hospital-based detection of Lynch syndrome distinguishes 2 types of
      microsatellite instabilities in colorectal cancers.
AB  - BACKGROUND: With progress in techniques of molecular biology, the phenotypes and
      genotypes for Lynch syndrome are more diverse than thought previously. This
      hospital-based study estimated the incidence and molecular and clinicopathologic
      features of Lynch syndrome to modify the screening criteria for Taiwanese
      patients with colorectal cancer (CRC). METHODS: A total of 561 CRC patients were
      enrolled. DNA was extracted from neoplasms, normal mucosa, and/or white blood
      cells for analyses of microsatellite instability (MSI), BRAF mutation, MLH1
      methylation, and sequencing of MMR genes. Immunohistochemistry (IHC) staining for
      MMR proteins was done for cases that fulfilled revised Bethesda criteria and for
      high-frequency microsatellite instability (MSI-H) neoplasms. RESULTS: There were
      136 (24.2%) and 10 (1.8%) cases that fulfilled the Revised Bethesda and Amsterdam
      II criteria (ACII), respectively. MSI-H was detected in 41 (7.3%), of which 32
      showed abnormalities for > or = 1 MMR protein by IHC; low-frequency MSI (MSI-L)
      or microsatellite stable showed abnormal MSH2 staining in only 1 of 117
      neoplasms. Thirteen (2.3%) cases had mutations in MMR genes with MLH1 (n = 10),
      MSH2 (n = 2), or MSH6 (n = 1). Of 13 Lynch syndrome cases, 3 (23.1%) and 11
      (84.6%) fulfilled ACII and revised Bethesda criteria, respectively; 12 cases
      (93.3%) were MSI-H, and all had expression loss of > or = 1 MMR protein. Eight
      patients were >50 years old, 2 of whom did not fulfill revised Bethesda criteria.
      For MSI-H neoplasms without definite mutations, 72.4% and 44.8% showed MLH1
      methylation and a BRAF (V599E) mutation, respectively. Lynch-associated CRC and
      sporadic MSI neoplasms shared similar clinicopathologic features. CONCLUSION: In
      Taiwan, the incidence of Lynch syndrome was 2.3% among the 561 CRC patients
      evaluated. For Taiwanese CRC patients who are younger than age 60 whether or not
      fulfilling the Bethesda criteria should receive MSI or IHC screening for
      identification of the Lynch syndrome.

PMID- 20045165
TI  - Administrative considerations when implementing ACS/APDS Skills Curriculum.
AB  - BACKGROUND: With time and cost constraints, implementing an effective, yet
      efficient, skills curriculum poses significant challenges. Our purpose is to
      describe a successful curriculum administrative structure that promoted faculty
      buy-in and accountability, learner responsibility, and acceptable resource usage.
      METHODS: A total of 14 American College of Surgery (ACS) modules were included in
      the postgraduate year 1 curriculum. Before arrival, 2 modules were sent to newly
      matched residents. Remaining modules were administered over a 4-month period,
      with integrated, independent practice opportunities, as well as 4 mentored and 1
      peer practice sessions. A total of 2 verifications of proficiency (VOP) progress
      exams and 1 final comprehensive VOP were administered. To promote faculty
      ownership, 1 faculty member was asked to lead each module. Module leaders
      attended an orientation and development session, and created an instructional
      management plan. Each module was taught by the leader and 2 additional faculty
      coinstructors, and evaluated by residents. Equipment, resource costs, and man
      hours were tracked. RESULTS: Faculty buy-in was demonstrated by enthusiastic
      participation, with only 2 absences. Residents gave high ratings to all the
      modules (range, 4.22-4.89/5). Curriculum costs were approximately $21,500,
      reduced from potential costs of $187,000 if all simulators would have been
      purchased new. The estimated budget for year 2 is $17,000. CONCLUSION: It is
      critical for new curricula to have resident and faculty buy-in, accountability
      for quality teaching and learning, and reasonable resource use. We provide
      suggestions for structuring a curriculum to ensure accomplishment of these
      important drivers.

PMID- 20045166
TI  - Effective velocity of 2D phononic crystals with rectangular lattice.
AB  - The effective velocity of elastic waves for two-dimensional (2D) phononic
      crystals with rectangular lattice in the long-wavelength limit is studied by
      numerical simulations. It is demonstrated that, for all three propagating modes,
      not only the modes polarized in-plane (L wave and SV wave), but also the mode
      polarized out-plane (SH wave), the effective velocities are distinctly
      anisotropic and the slowness curves exhibit twofold symmetry. The anisotropy
      increases as the filling fraction increases or as the width to length ratio of
      the lattice decreases, and high anisotropy can be obtained in phononic crystals
      with large contrast between material parameters, which is much higher in
      rectangular lattice than in square lattice with the same material parameters.
      Owing to these dependences, the effective velocity can be controlled in
      engineering.

PMID- 20045167
TI  - Drinking water treatment of priority pesticides using low pressure UV photolysis
      and advanced oxidation processes.
AB  - This study reports the efficiency of low pressure UV photolysis for the
      degradation of pesticides identified as priority pollutants by the European Water
      Framework Directive 2000/60/EC. Direct low pressure UV photolysis and advanced
      oxidation processes (using hydrogen peroxide and titanium dioxide) experiments
      were conducted in laboratory grade water, surface water, and groundwater. LP
      direct photolysis using a high UV fluence (1500 mJ/cm(2)) was found to be
      extremely efficient to accomplish the degradation of all pesticides except
      isoproturon, whereas photolysis using hydrogen peroxide and titanium dioxide did
      not significantly enhance their removal. In all matrices tested the experimental
      photolysis of the pesticides followed the same trend: isoproturon degradation was
      negligible, alachlor, pentachlorophenol, and atrazine showed similar degradation
      rate constants, whereas diuron and chlorfenvinphos were highly removed. The
      degradation trend observed for the selected compounds followed the decadic molar
      absorption coefficients order with exception of isoproturon probably due to its
      extremely low quantum yield. Similar direct photolysis rate constants were
      obtained for each pesticide in the different matrices tested, showing that the
      water components did not significantly impact degradation. Extremely similar
      photolysis rate constants were also obtained in surface water for individual
      compounds when compared to mixtures. The model fluence and time-based rate
      constants reported were very similar to the direct photolysis experimental
      results obtained, while overestimating the advanced oxidation results. This model
      was used to predict how degradation of isoproturon, the most resilient compound,
      could be improved.

PMID- 20045168
TI  - Achieving biofilm control in a membrane biofilm reactor removing total nitrogen.
AB  - Membrane biofilm reactors (MBfR) utilize membrane fibers for bubble-less transfer
      of gas by diffusion and provide a surface for biofilm development. Nitrification
      and subsequent autotrophic denitrification were carried out in MBfR with pure
      oxygen and hydrogen supply, respectively, in order to remove nitrogen without the
      use of heterotrophic bacteria. Excessive biomass accumulation is typically the
      major cause of system failure of MBfR. No biomass accumulation was detected in
      the nitrification reactor as low-level discharge of solids from the system
      balanced out biomass generation. The average specific nitrification rate during
      250 days of operation was 1.88gN/m(2)d. The subsequent denitrification reactor,
      however, experienced decline of performance due to excessive biofilm growth,
      which prompted the implementation of periodic nitrogen sparging for biofilm
      control. The average specific denitrification rate increased from 1.50gN/m(2)d to
      1.92gN/m(2)d with nitrogen sparging, over 190 days thus demonstrating the
      feasibility of stable long-term operation. Effluent suspended solids increased
      immediately following sparging: from an average of 2.5mg/L to 12.7mg/L. This
      periodic solids loss was found unavoidable, considering the theoretical biomass
      generation rates at the loadings used. A solids mass balance between the
      accumulating and scoured biomass was established based on the analysis of the
      effluent volatile solids data. Biofilm thickness was maintained at an average of
      270microm by the gas sparging biofilm control. It was concluded that biomass
      accumulation and scouring can be balanced in autotrophic denitrification and that
      long-term stable operation can be maintained.

PMID- 20045169
TI  - Indigenous somatic coliphage removal from a real municipal wastewater by a
      submerged membrane bioreactor.
AB  - The membrane bioreactor (MBR) features many advantages, such as its excellent
      effluent quality and compactness. Moreover, the MBR is well known for its
      disinfectant capacity. This paper investigates virus removal performance for
      municipal wastewater using a submerged MBR and the operational conditions
      affecting the virus removal using indigenous somatic coliphages (SC) as an
      indicator for viruses. The results revealed that the municipal wastewater
      acquired by the Qinghe Municipal Wastewater Treatment Plant, Beijing, contained
      an SC concentration of (2.81+/-1.51)x10(4)PFU ml(-1), which varies seasonally due
      to spontaneous decay. In the MBR system, the biomass process dominates SC
      removal. Membrane rejection is an essential supplement of biomass process for SC
      removal. In this paper, the relative contributions of biomass process and
      membrane rejection during the start-up and steady operational periods are
      discussed in detail. The major factors affecting SC removal are biodegradation,
      membrane pore size, and gel layer formation on the membrane. During long-term
      experiments, it was demonstrated that high inoculated sludge concentration, long
      hydraulic retention time, moderate fouling layer, and non-frequent chemical
      cleaning are favorable for high SC removal in MBR systems.

PMID- 20045170
TI  - Removal of bromide and natural organic matter by anion exchange.
AB  - Bromide removal by anion exchange was explored for various water qualities,
      process configurations, and resin characteristics. Simulated natural waters
      containing different amounts of natural organic matter (NOM), bicarbonate,
      chloride, and bromide were treated with a polyacrylate-based magnetic ion
      exchange (MIEX) resin on a batch basis to evaluate the effectiveness of the resin
      for removal of bromide. While bromide removal was achieved to some degree,
      alkalinity (bicarbonate), dissolved organic carbon (DOC), and chloride were shown
      to inhibit bromide removal in waters with bromide concentrations of 100 and 300
      microg/L. Water was also treated using a two-stage batch MIEX process. Two-stage
      treatment resulted in only a slight improvement in bromide removal compared to
      single-stage treatment, presumably due to competition with the high concentration
      of chloride which is present along with bromide in natural waters. In view of the
      relatively poor bromide removal results for the MIEX resin, a limited set of
      experiments was performed using polystyrene resins. DOC and bromide removal were
      compared by treating model waters with MIEX and two polystyrene resins, Ionac A
      641 and Amberlite IRA910. The two polystyrene resins were seen to be more
      effective for bromide removal, while the MIEX resin was more effective at
      removing DOC.

PMID- 20045171
TI  - Subcellular compartmentalization of cadmium, nickel, and lead in Gammarus
      fossarum: Comparison of methods.
AB  - Knowledge of the subcellular behavior of toxicants, mainly metals, in living
      organisms is fundamental for understanding their toxicological consequences at
      individual and trans-generation levels and throughout the food web. However,
      different partitioning methodologies are available in the literature,
      particularly concerning the cytosolic fraction. Different cytosolic compounds,
      metallothionein-like proteins (MTLPs), and non-metallothionein-like proteins (non
      MTLPs) could be separated by size exclusion chromatography or by heat treatment
      and centrifugation. Our results show changes of metal partitioning in the
      cytosolic fraction according to the methodologies used. After heat treatment, the
      majority of cytosolic cadmium (Cd) was found with MTLPs compounds and the
      opposite results were observed with size exclusion chromatography. Metal
      partitioning could also play an important role in the metal trophic transfer.
      Therefore, metal partitioning in Gammarus fossarum, an ecologically relevant
      species and good metal bioaccumulator, defining the trophically available metal
      fraction, is also discussed.

PMID- 20045172
TI  - Congener specific analysis of polychlorinated terphenyls.
AB  - In order to identify and to quantify polychlorinated terphenyls (PCT) in
      environmental matrices, the chromatographic behavior of coplanar and non-coplanar
      congeners was evaluated. A mixture of 16 single PCT congeners was used for method
      development. Four of these compounds were synthesized for the first time by
      SUZUKI-coupling reaction. These were p-PCT (2,2'',6,6''-tetrachloro-,
      2',3,3'',4,4'',5',-hexachloro-, 2',3,3'',5,5',5''-hexachloro-) and m-PCT
      (2,2'',3,3'',5,5''-hexachloro-). They were characterized by NMR ((1)H,(13)C)
      spectroscopy. By means of the new column chromatographic clean-up reported here,
      a good matrix removal and the separation of the coplanar PCT congeners from the
      non-coplanar ones was obtained. The recovery rates for all congeners were good
      for the PCT in different test matrices like fat, charcoal, and soil. The quality
      of the clean-up, the separation and the recovery rates were determined by GC/MS
      analysis. The method was applied for the first time to a real sample from a fire
      accident, where different PCT, obviously formed during the combustion process,
      were found. The conclusion is drawn that this method is suitable for the analysis
      of PCT in different environmental samples.

PMID- 20045173
TI  - High levels of polychlorinated dibenzo-dioxins/furans and dioxin like-PCBs found
      in monitoring investigations of sheep liver samples from Lower Saxony, Germany.
AB  - In this study, the occurrence of 17 toxicologically-relevant polychlorinated
      dibenzo-dioxins and furans (PCDD/PCDFs) and 12 dioxin-like polychlorinated
      biphenyls (dl-PCBs) was investigated in livers of sheep from Lower Saxony,
      Germany. The aim of the monitoring was to get a state-wide picture on the
      contamination level of sheep liver samples. Seventy two out of 77 investigated
      sheep liver samples exceeded the European maximum tolerance level for PCDD/PCDFs
      of 6.0 pg WHO-PCDD/F-TEQ g(-1) fat with measured average, median and maximum
      values of 23.9, 18.3 and 161 pg WHO-PCDD/F-TEQ g(-1) fat, respectively. Seventy
      one samples also exceeded the cumulative maximum tolerance level of 12.0 pg WHO
      PCDD/F-PCB-TEQ g(-1) fat set in the EU for the sum of PCDD/PCDFs and dl-PCBs in
      livers of sheep and derived products. Average, median and maximum measured values
      were 42.9, 33.9 and 204 pg WHO-PCDD/F-PCB-TEQ g(-1) fat, respectively. In the
      meat of the sheep only low amounts of PCDD/Fs or dl-PCBs were detected that never
      exceeded the respective maximum tolerance levels. The results did not show any
      significant differences in contamination between female or male sheep. Also no
      correlation was found between the age of the animals and the burden of their
      livers with PCDD/PCDFs or dl-PCBs. Health risks from the casual consumption of
      sheep livers are almost unlikely but can also not be excluded for individuals
      frequently consuming sheep livers with average contamination levels. Almost no
      difference was observed in the burden of contamination of sheep liver samples
      between rural and municipal areas or between areas located near or apart from
      waterways. In conclusion, the results yielded a picture of a varying but high
      level of contamination of sheep livers most likely caused by physiological
      differences compared to other animal species and by the ubiquitous environmental
      contamination primarily assignable to historic dioxin and PCB sources.

PMID- 20045174
TI  - Mobilization of hydrophobic contaminants from soils by enzymatic depolymerization
      of soil organic matter.
AB  - The effect of hydrolytic exoenzymes on the release of hydrophobic organic
      contaminants (HOC) from two different surface soils was studied in laboratory
      batch experiments. Incubation of the soils with cellulase with an activity
      fivefold above the inherent soil activity enhanced the release of hydrophobic
      contaminants (polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls
      (PCB) and hydroxylated PCB) by 40-200%. Xylanase and invertase did not show
      measurable effects at comparable relative activity levels. This suggests that
      cellulose substructures are important for the retention of HOC in soil organic
      matter (SOM). Hydrolytic exoenzymes, and the microorganisms that release them,
      contribute to the mobilization of HOC from soil, by shifting the sorption
      equilibrium in the course of SOM transformation into dissolved organic matter or
      by facilitating HOC diffusion as a consequence of reduced rigidity of SOM. We
      conclude that not only biodegradation but also sorption and desorption of HOC in
      soil can be influenced by (micro-) biology and the factors that determine its
      activity.

PMID- 20045175
TI  - Characterization and aerosol mass balance of PM2.5 and PM10 collected in Conakry,
      Guinea during the 2004 Harmattan period.
AB  - Background PM(2.5) and PM(10) levels were determined during Harmattan (West
      African wind blown dust) at a background site in Conakry, Guinea. The study was
      conducted from January to February, 2004 when Harmattan dust appeared to be most
      pronounced. PM(2.5) concentrations at the Nongo American housing compound ranged
      from 38mugm(-3) to 177mugm(-3), and PM(10) ranged from 80mugm(-3) to 358mugm(-3),
      exceeding standards set by EPA and European Commission Environment Directorate
      General. PTFE filter samples were analyzed for insoluble and soluble inorganic
      constituents by XRF and IC, respectively. Sulfur and associated SO(4)(2-)
      concentrations were notably consistent among PM(2.5) and PM(10) samples which
      marked a relatively stable S background signal from anthropogenic sources.
      Enrichment factor (EF) analysis and aerosol mass reconstruction (AMR) techniques
      were used to isolate potential PM source contributors. The EF's for SiO(2),
      TiO(2), Al(2)O(3), Fe(2)O(3), and MnO were near unity which suggests a crustal
      origin for these elements. EF's for Na(2)O and K(2)O were above unity and highly
      variable, these elements were elevated due to widespread mangrove wood combustion
      as a fuel source in Conakry. The EF's for Cr were notably high with a median of 7
      and interquartile range from 5 to 16, the elevated levels were attributed to
      unregulated point source and mobile source emitters in and around Conakry.

PMID- 20045176
TI  - Immunolocalization of corticotropin-releasing factor (CRF) and corticotropin
      releasing factor receptor 2 (CRF-R2) in the developing gut of the sea bass
      (Dicentrarchus labrax L.).
AB  - Our previous data indicated an important role for adrenocorticotropic (ACTH)-like
      molecules co-operating with macrophages to control the modifications in body
      homeostasis during the first period of the life of sea bass (up to 30 days post
      hatching) before the lymphoid cells have reached complete maturation. The aim of
      the study was to determine the immunolocalization of corticotropin-releasing
      factor (CRF), which is a very important mediator of stress-related responses. Our
      data showed that immunostaining for CRF is localized already at 8 days after
      hatching in nerve fibers of the gastrointestinal tract wall from the pharynx to
      the anterior gut, when the larvae are still feeding on yolk. This pattern of
      immunolocalization appeared similar to that in 24-day-old larvae, but at this
      stage there were also large cells immunopositive to CRF located in the wall of
      the midgut and hindgut. Lipopolysaccharide (LPS) treatment, which is a known
      stimulator of stress hormone responses, did not modify the CRF immunostaining
      pattern, though it did affect the immunolocalization of the peripheral CRF
      receptor, i.e. CRF-R2. Immunolocalization of CRF-R2 appeared in nerve fibers of
      the gut wall in larvae fixed 1h after the end of lipopolysaccharide (LPS)
      treatment. The present results suggest that CRF plays important autocrine and/or
      paracrine roles in the early immune responses at the gut level in the larval
      stages of sea bass (Dicentrarchus labrax L.) as already proposed for ACTH.
      Moreover, our studies taken together with other research on fish, in comparison
      with mammals, suggest a phylogenetically old role of CRF in immune-endocrine
      interactions.

PMID- 20045177
TI  - Chlorhexidine stabilizes the adhesive interface: a 2-year in vitro study.
AB  - OBJECTIVES: This study evaluated the role of endogenous dentin MMPs in auto
      degradation of collagen fibrils within adhesive-bonded interfaces. The null
      hypotheses tested were that adhesive blends or chlorhexidine digluconate (CHX)
      application does not modify dentin MMPs activity and that CHX used as therapeutic
      primer does not improve the stability of adhesive interfaces over time. METHODS:
      Zymograms of protein extracts from human dentin powder incubated with Adper
      Scotchbond 1XT (SB1XT) on untreated or 0.2-2% CHX-treated dentin were obtained to
      assay dentin MMPs activity. Microtensile bond strength and interfacial
      nanoleakage expression of SB1XT bonded interfaces (with or without CHX pre
      treatment for 30s on the etched surface) were analyzed immediately and after 2
      years of storage in artificial saliva at 37 degrees C. RESULTS: Zymograms showed
      that application of SB1XT to human dentin powder increases MMP-2 activity, while
      CHX pre-treatment inhibited all dentin gelatinolytic activity, irrespective from
      the tested concentration. CHX significantly lowered the loss of bond strength and
      nanoleakage seen in acid-etched resin-bonded dentin artificially aged for 2
      years. SIGNIFICANCE: The study demonstrates the active role of SB1XT in dentin
      MMP-2 activation and the efficacy of CHX inhibition of MMPs even if used at low
      concentration (0.2%).

PMID- 20045178
TI  - Review of the fracture toughness approach.
AB  - Dental adhesives are usually tested in shear or tension even though neither of
      these approaches measures the local stress triggering failure. Because the stress
      level varies extensively over the bonded surface, it seems as a fracture
      mechanics approach would be more appropriate. In this review different general
      aspects of fracture mechanics and adhesive joints were reviewed first. That
      review served as a foundation for a review of fracture toughness studies
      performed on dental adhesives. The dental adhesive studies were identified
      through a MEDLINE search using "dental adhesion testing AND enamel OR dentin AND
      fracture toughness" as search strategy. The outcome of the review revealed that
      fracture toughness studies performed on dental adhesives are complex, both
      regarding technical performance as well as achieving good discriminating ability
      between different adhesives. The review also suggested that most fracture
      toughness tests of adhesives performed in dentistry are not totally reliable
      because they usually did not consider the complex stress pattern at the adhesive
      interface. However, despite these limitations, the review strongly supports the
      notion that the proper way of studying dental adhesion is by use a fracture
      mechanics. At the present time, it seems as the fracture energy of adhesives
      might be more appropriate to determine than their fracture toughness values.

PMID- 20045179
TI  - Adhesion to tooth structure: a critical review of "micro" bond strength test
      methods.
AB  - The objective of this paper is to critically review the literature regarding the
      mechanics, geometry, load application and other testing parameters of "micro"
      shear and tensile adhesion tests, and to outline their advantages and
      limitations. The testing of multiple specimens from a single tooth conserves
      teeth and allows research designs not possible using conventional 'macro'
      methods. Specimen fabrication, gripping and load application methods, in addition
      to material properties of the various components comprising the resin-tooth
      adhesive bond, will influence the stress distribution and consequently, the
      nominal bond strength and failure mode. These issues must be understood; as
      should the limitations inherent to strength-based testing of a complicated
      adhesive bond joining dissimilar substrates, for proper test selection, conduct
      and interpretation. Finite element analysis and comprehensive reporting of test
      conduct and results will further our efforts towards a standardization of test
      procedures. For the foreseeable future, both "micro" and "macro" bond strength
      tests will, as well as various morphological and spectroscopic investigative
      techniques, continue to be important tools for improving resin-tooth adhesion to
      increase the service life of dental resin-based composite restorations.

PMID- 20045180
TI  - The biocompatability of mesoporous inorganic-organic hybrid resin films with
      ionic and hydrophilic characteristics.
AB  - New mesoporous silicate-titania resin systems hybridized with 4,5-dihydroxy-m
      benzenedisulfonic acid and poly(ethylene glycol)-dimethacrylate component were
      developed. These inorganic-organic hybrid resins were found to reveal highly
      controlled ionic and hydrophilic surface with excellent durability and adhesion
      onto various substrates. The resin films revealed high resistance to nonspecific
      adsorption of fibrinogen and to adherence by several bacterial pathogens such as
      Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and
      Enterococcus faecalis. Furthermore, excellent biocompatibility of the developed
      resins was proved by both HEp-2 cell adhesion in vitro and subcutaneous
      implantation in mice. The inorganic-organic hybrid resins are strongly promising
      for biomedical applications including biomedical devices and biosensors.

PMID- 20045181
TI  - Targeting of the prostacyclin specific IP1 receptor in lungs with molecular
      conjugates comprising prostaglandin I2 analogues.
AB  - Molecular conjugates comprising targeting ligands hold great promise for site
      specific gene delivery to distant tumors and individual organs including the
      lung. Here we show that prostaglandin I2 analogues can be used to improve gene
      transfer efficiency of polyethylenimine (PEI) gene vectors on bronchial and
      alveolar epithelial cells in vitro and lungs of mice in vivo. Prostacyclin (IP1)
      receptor expression was confirmed in pulmonary epithelial cell lines by western
      blot. Iloprost (ILO) and treprostinil (TRP), two prostaglandin I2 analogues, were
      conjugated to fluorescein-labeled BSA (FLUO-BSA) and compared for IP1 receptor
      binding/uptake in different lung cell lines. Binding of FLUO-BSA-ILO was 2-4-fold
      higher than for FLUO-BSA-TRP and could be specifically inhibited by free ILO and
      IP1 receptor antagonist CAY10449. Internalization of FLUO-BSA-ILO was confirmed
      by confocal microscopy. Molecular conjugates of PEI and ILO (PEI-g-ILO) were
      synthesized with increasing coupling degree (F(ILO) (ILO:PEI) = 2, 5, 8, 16) and
      analyzed for DNA binding, particle formation and transfection efficiency. At
      optimized conditions (N/P 4, F(ILO) = 5), gene expression using PEI-g-ILO was
      significantly up to 46-fold higher than for PEI gene vectors and specifically
      inhibited by CAY10449. Gene expression in the lungs of mice after aerosol
      delivery was 14-fold higher with PEI-g-ILO F(ILO) = 5 than for PEI. We suggest
      that targeting of IP1 receptor using ILO represents a promising approach to
      improve pulmonary gene transfer.

PMID- 20045182
TI  - pH responsive properties of non-fouling mixed-charge polymer brushes based on
      quaternary amine and carboxylic acid monomers.
AB  - In this work, we report a tunable mixed-charge copolymer surface containing
      positively charged quaternary amine monomers ([2-(acryloyloxy)ethyl] trimethyl
      ammonium chloride, TMA) and negatively-charged carboxylic acid monomers (2
      carboxy ethyl acrylate, CAA). The non-fouling properties of this copolymer
      coating depend on environmental pH. The surface has charge neutrality under
      neutral and basic conditions, and is positively charged under acidic conditions
      due to the protonation of the carboxylic acid group. This transition in surface
      charge with respect to pH allows the surface to be switched from bacteria
      adhesive to bacteria-resistant. We demonstrate that the bacteria adhered to the
      surface under acidic conditions can be easily released as bulk pH increases. This
      tunable surface can be used to collect a contaminant and then be externally
      stimulated to release the contaminant, to allow for analysis of its composition.
      Its bacteria attraction and release property makes it very promising for
      decontamination and biomedical applications.

PMID- 20045183
TI  - Evaluation of polymer matrices for an adsorptive approach to plasma
      detoxification.
AB  - Acute liver failure arises when potentially toxic metabolites accumulate in the
      bloodstream because of a breakdown in liver function. New extracorporeal systems
      combining membrane and adsorbent technologies are being developed to replace
      critical liver detoxification functions between diagnosis and transplantation.
      This study addresses the adsorption of representative plasma components on four
      different hydrophobic, polymeric adsorbents for possible use in an extracorporeal
      hemodialysis device. The adsorbents considered span a range of pore sizes and
      include both strongly hydrophobic divinylbenzene (DVB) matrices as well as a less
      hydrophobic acrylate matrix. Adsorption equilibrium and rate measurements were
      made for these matrices using human serum albumin (HSA), polyclonal human
      immunoglobulin G (IgG), and bilirubin (BR), as representative plasma components.
      Pore size was found to contribute significantly to selectivity. Results
      demonstrated that strongly hydrophobic materials with pore sizes that allow free
      access to protein-bound BR are most effective for BR removal whether they are
      initially clean or pre-saturated with HSA.

PMID- 20045184
TI  - Dexamethasone stimulates placental system A transport and trophoblast
      differentiation in term villous explants.
AB  - Synthetic glucocorticoids (GCs) are given to women with threatened preterm labour
      but their administration has been linked to reduced infant birthweight. The
      underlying mechanisms are unknown, but impaired placental development and/or
      function has been implicated. The activity of the system A amino acid transporter
      is decreased in placentas from pregnancies complicated by fetal growth
      restriction. Whether GCs adversely affect placental amino acid transport is
      unknown. The objective of this study was to determine the regulatory effects of
      GCs on system A transport using a human in vitro placental explant model. Term
      explants (n=7) were treated with dexamethasone (DEX 10(-8)M or 10(-6)M) or
      vehicle for 48 h. System A activity was measured by the uptake of (14)C-N
      methylated aminoisobutyric acid by explants. Explants were also processed for
      electron microscopy (EM), immunohistochemistry, and qRT-PCR. Lactate
      dehydrogenase (LDH), human chorionic gonadotropin (hCG) and human placental
      lactogen (hPL) release into the culture medium was measured. DEX (10(-6)M)
      stimulated system A activity compared to vehicle (p<0.05). System A transporter
      proteins were localized to the newly regenerating syncytiotrophoblast layer, but
      mRNA levels were unchanged with DEX treatment. DEX did not adversely affect
      explant viability as determined by reduced LDH release (p<0.05). DEX treatment
      was associated with morphological (accelerated apical microvilli formation,
      nuclear maturation, and increased cell organelle number) and functional (elevated
      hCG secretion, increased 11beta-HSD2 mRNA expression and reduced cytotrophoblast
      proliferation (p<0.05 for all)) markers of syncytiotrophoblast differentiation.
      These findings suggest that DEX stimulates system A activity and promotes
      syncytiotrophoblast differentiation and maturation.

PMID- 20045185
TI  - Peroxisome proliferator-activated receptors are altered in pathologies of the
      human placenta: gestational diabetes mellitus, intrauterine growth restriction
      and preeclampsia.
AB  - BACKGROUND: Common complications of pregnancy arise in part from dysfunctional
      placental development, and include gestational diabetes mellitus (GDM),
      intrauterine growth restriction (IUGR) and preeclampsia (PE). Peroxisome
      proliferator-activated receptors (PPARs), and their partner retinoid X receptor a
      (RXRalpha), mediate trophoblast differentiation and thus may offer insight into
      the pathophysiology of these diseases. METHODS: Human placentae were obtained
      from women at term with GDM and were compared to uncomplicated term placentae.
      Placentae from women who delivered preterm with IUGR, PE or co-existing PE and
      IUGR were compared to matched controls. Quantitative RT-PCR and Western blotting
      were used to examine mRNA and protein expression of PPARalpha, PPARdelta,
      PPARgamma and RXRalpha. DNA binding activity of PPAR isoforms were measured in
      nuclear protein extracts. RESULTS: GDM was associated with significantly lower
      placental PPARgamma mRNA and protein, PPARalpha protein and RXRalpha protein
      expression, while PPAR DNA binding activity remained unchanged. Placentae from
      women with PE did not demonstrate any changes in mRNA or protein expression or
      PPAR DNA binding activity, while IUGR/PE placenta showed significant increases in
      PPARalpha protein, PPARgamma mRNA and protein and RXRalpha mRNA and protein
      expression. Significantly elevated protein expression of PPARalpha and RXRalpha
      were associated with IUGR placentae. IUGR and IUGR/PE placentae had significantly
      higher PPARgamma DNA binding activity compared to controls. CONCLUSIONS: The data
      presented herein suggest that PPARs may be involved in the pathophysiology of
      GDM, PE and IUGR.

PMID- 20045186
TI  - Glial calcium and diseases of the nervous system.
AB  - The evolution of the central nervous system (CNS) resulted in an appearance of
      highly specialised neuronal networks optimised for rapid information transfer. In
      the course of this specialisation neuronal cells lost their metabolic
      independence and the ability to survive in the absence of homeostatic systems.
      These homeostatic systems, represented by neuroglia regulate all aspects of CNS
      function in physiological and pathological conditions. The neurological diseases
      should be therefore considered as primary gliopathologies, which determine the
      progression and outcome of neuropathological process. Glial function is
      intimately regulated by cellular calcium signalling that underlies the specific
      form of "glial calcium excitability". Glial Ca2+ signals are triggered by
      activation of multiple receptors, and are primarily driven by Ca2+ release from
      the endoplasmic reticulum. In this review we summarise the role of glial calcium
      signalling in various forms of pathological processes including neurological and
      psychiatric disorders and neurodegeneration.

PMID- 20045187
TI  - Calcium and normal brain ageing.
AB  - Normal brain ageing is associated with a varying degree of cognitive impairment.
      Although ageing is a complex, multifactorial process, and no single process could
      explain the ageing phenotype, a number of processes and homeostatic systems, due
      to their central roles in cellular physiology, have been identified as playing
      important roles in the process of normal ageing. In this review we revisit the
      basic tenets of the Ca2+ hypothesis of neuronal ageing and stress the major
      conceptual changes that occurred between the time of its original proposal and
      now, in particular in respect to the extent of neuronal loss in normal ageing. We
      provide a general overview of the most important ageing-associated changes in
      neuronal Ca2+ homeostasis and then discuss in some detail how such homeostatic
      changes are affecting basic neuronal properties, such as intrinsic excitability
      and how, by extension, such changes could lead to significant perturbations in
      the activity of whole neuronal network ensembles. Since some of these network
      activities, such as the synchronisation of neuronal activity in the gamma
      frequency range, have been linked to learning and cognition, understanding the
      metabolic substrates and homeostatic dysregulation that underpin them could
      provide a novel basis for attempts at counteracting the cognitive decline of
      older individuals.

PMID- 20045188
TI  - Effect of kinin B2 receptor ablation on skeletal muscle development and myostatin
      gene expression.
AB  - Bradykinin (BK) is an active peptide that binds to the kinin B(2) receptor and
      induces biological events during the development and adult life. In this study we
      aimed to investigate the effect of kinin B(2) receptor ablation in the postnatal
      skeletal muscle development and body composition in adult life. For studies of
      skeletal muscle development, control (C57Bl6 - WT) and B(2) receptor knockout
      mice (B(2)(-/-)) were sacrificed at 15, 30 and 90days after birth, the
      gastrocnemius skeletal muscle was weighed and myostatin gene expression evaluated
      by real time PCR. For energy balance determination, data from control and B(2)(-/
      ) at 90 and 120days were collected by calorimetric method. Body composition at
      120days was determined by chloroform-methanol (total body fat) and Lowry-modified
      method (total body protein). The results show that B(2)(-/-) have significantly
      increased total body weight at 15, 30 and 90days of life, when compared to WT.
      The weight of the gastrocnemius skeletal muscle was also significantly increased
      at 30 and 90days of life. Body composition analyses revealed that B(2)(-/-) mice
      exhibit more total corporal protein and less total corporal fat. Energy balance
      revealed that B(2)(-/-) have increased metabolizable energy intake and energy
      expenditure when compared to control mice, resulting in a lower energy gain.
      Interestingly, myostatin mRNA expression was significantly decreased in 15 and
      30days old B(2)(-/-) mice and after icatibant treatment of WT adult mice for
      5days. In conclusion, together our results show that kinin B(2) receptor deletion
      increases lean mass, reduces fat mass and improves metabolism efficiency in mice.
      The mechanism involved in this phenotype could be related to the reduction of
      myostatin gene expression during postnatal life.

PMID- 20045189
TI  - Distribution and expression of B2-kinin receptor on human leukocyte subsets in
      young adults and elderly using flow cytometry.
AB  - The kallikrein-kinin system has been investigated in many experimental models.
      Dysregulations of the KKS are likely to be involved in pathologies such as
      inflammation, cancer and cardiovascular diseases. Previous works on the human KKS
      mostly rely on gene polymorphism and mRNA expression. In order to assess the KKS
      in human at the protein level, we have developed an approach based on flow
      cytometric analysis of leukocytes. Whole blood samples were collected and
      erythrocytes were lysed. Permeabilised leukocytes were incubated with anti-B2R
      (IgG2b), anti-IgG2b-PE, anti-CD3-PerCP (lymphocytes) and anti-CD14-APC
      (monocytes) antibodies. FACScalibur analyzed fluorescence intensities. Results
      were expressed as per cent of B2R-positive cells in each leukocyte subset and as
      B2R fluorescence intensity per positive cell. Detection of the B2R protein by
      this methodology was validated by (i) correlation with Western blotting using two
      different B2R antibodies, (ii) BK-induced Erk activation, (iii) B2R mRNA
      expression. The methodology was then applied to evaluate variations of B2R
      expression in a population including young healthy, elderly healthy, and elderly
      treated hypertensive men and women. In the young healthy subjects, B2R
      distribution was: monocytes>polymorphonuclear neutrophils (PMN)>lymphocytes and
      no difference with gender was observed. Moreover, no difference was observed on
      PMN B2R expression. B2R expression remained unchanged in the elderly healthy or
      hypertensive men. By contrast, monocytes and lymphocytes B2R expressions were
      decreased in the elderly healthy women. Finally, FACS analysis of B2R expression
      on leukocytes subsets provides single cell quantification of B2R expression
      allowing comparison of cellular sub-populations. This approach provides a new
      efficient tool to investigate B2R profiling of immune system in pathological
      states.

PMID- 20045190
TI  - Pre-treatment with mild UV irradiation suppresses reproductive toxicity induced
      by subsequent cadmium exposure in nematodes.
AB  - In nematodes, 10 J/m(2)/min of UV irradiation induced a mild reproductive
      toxicity. Pre-treatment with UV irradiation at 10 J/m(2)/min suppressed the
      formation of reproductive defects, and activated a noticeable reduction of
      percentage of population with hsp-16.2::gfp expression, an obvious elevation of
      superoxide dismutase activities, and decrease of oxidative damage in 50 and 100
      microM Cd exposed nematodes; however, pre-treatment with UV irradiation at 20
      J/m(2)/min caused a significant decrease of brood sizes or increase of generation
      times in Cd-exposed nematodes. Pre-treatment with mild UV irradiation did not
      suppress the formation of reproductive defects in 150 microM Cd-exposed
      nematodes. Furthermore, the adaptive response to reproductive toxicity from Cd
      exposure was not observed in a reactive oxygen species sensitive mev-1(kn1)
      mutant. Therefore, pre-treatment with mild UV irradiation triggers the resistance
      to reproductive toxicity from Cd exposure by at least partially inducing
      adaptation to oxidative stress and through a mev-1-dependent pathway.

PMID- 20045191
TI  - Effect of different microcystin profiles on toxin bioaccumulation in common carp
      (Cyprinus carpio) larvae via Artemia nauplii.
AB  - In this study, a 12-day growth trial was conducted to compare the effect of the
      variation in microcystin (MC) composition in two Microcystis aeruginosa bloom
      samples on the growth performance and MC accumulation/transfer in the common carp
      (Cyprinus carpio L.) larvae. Fish were fed Artemia salina nauplii that had been
      preexposed to extracts from two M. aeruginosa natural blooms with different
      microcystins (MCs) profiles. Bloom A had MC-LR as major toxin (74.05%) while
      bloom B had a diversity of MC (MC-RR; MC-(H4)YR; MC-YR; MC-LR; MC-FR; MC-WR) with
      no dominance of MC-LR. Newly-hatched Artemia nauplii were exposed separately to
      the two M. aeruginosa extracts A and B (100 microg L(-1)EqMC-LR) for 2h. The MC
      concentration in the nauplii was 73.60+/-7.88ngEqMC-LRg(-1)FW (n=4, mean+/-SE)
      for bloom A and 87.04+/-10.31ngEqMC-LRg(-1)FW for bloom B. These contaminated
      nauplii were given at the same ration to different groups (A and B) of fish
      larvae. Larval weight and length from day 9 were significantly different between
      groups A and B, and in both cases lower than that of a control group fed non
      exposed nauplii. MCs accumulation by larvae, inversely correlated with the growth
      performance, was also significantly different between groups A and B (37.43+/
      2.61 and 54.55+/-3.01ngEqMC-LRg(-1) FW, respectively, at the end of the
      experimental period). These results indicate that MC profile of a bloom may have
      differential effects on toxin accumulation/transfer and toxicity.

PMID- 20045192
TI  - Effects of sodium dodecylbenzene sulfonate and sodium dodecyl sulfate on the
      Mytilus galloprovincialis biomarker system.
AB  - The effects of in vivo exposure of Mytilus galloprovincialis to two anionic
      surfactants (SDBS and SDS) on the molecular biomarker system were studied. After
      continuous exposure for 72 days, activities/levels of GST, GPx and GSH were
      significantly higher than in corresponding control groups following exposure to
      3.000 mg/L SDS and SDBS. Activities of SOD and CAT were significantly inhibited
      by experimental SDBS (except CAT in 0.100mg/L group), but not by SDS. Statistical
      analysis of enzyme activities/levels suggested that there were significant
      positive relationships between GST and GPx, and negative relationships were found
      between GSH and CAT, GSH and SOD. Amplified fragment length polymorphism (AFLP)
      results showed that a greater genotoxic effect was observed for SDBS than for
      SDS. Based on the above results, the biomarker system of mussels can be affected
      by the two anionic surfactants (>or=3.000 mg/L); it was more easily affected by
      SDBS than by SDS.

PMID- 20045193
TI  - Ecological significance of hazardous concentrations in a planktonic food web.
AB  - Species sensitivity distributions (SSDs) are statistical distributions that are
      used to estimate the potentially affected fraction (PAF) of species at a given
      toxicant concentration, the hazardous concentration for that fraction of species
      (HC(PAF)). Here, we use an aquatic food web model that includes 14 phytoplankton
      and 6 zooplankton species to estimate the number of species experiencing a
      biomass reduction when the food web is exposed to the HC(PAF) and this for 1000
      hypothetical toxicants and for PAF=5-30%. When choosing a 20% decrease as a cut
      off to categorize a species' biomass as affected, 0-1 and 2-5 out of the 20
      species were affected at the HC(5) and HC(30), respectively. From this, it can be
      concluded that the PAF is a relatively good estimator of the number of affected
      species. However, when phytoplankton species experiencing >or=20% biomass
      increase were also classified as affected, the number of affected species
      predicted by the food web model varied strongly among toxicants for PAF >5, with
      2-16 out of 20 species affected at the HC(30). Phytoplankton species with extreme
      (both high and low) values for uptake rates and light limitation constants
      experienced smaller effects on their biomass than phytoplankton species with more
      average parameter values. We conclude that, next to measures of toxicity,
      ecological characteristics of species may help understanding ecological effects
      occurring in ecosystems also.

PMID- 20045194
TI  - Causes in the construction of causal law: A psycho-ecological model.
AB  - The article presents an integrated psycho-ecological model of the construction of
      law, with implications for practice in law and mental health. The model is based
      on a series of concentric circles, each representing a layer of influence on the
      construction of law. The circle furthest removed from the center represents the
      influence of culture, society and industry, in particular, and the circle at the
      center of the circle represents the case at hand, for example, about individual
      complainant or mass action. The article begins by arguing that basic terms in
      relation to cause need clarification and also work is needed to disambiguate the
      concepts involved. After dealing with these issues, the article examines science
      and mental health. Is the scientific evidence presented by the expert
      sufficiently reliable and valid to meet admissibility standards of good compared
      to poor or junk science? Is the research undertaken for court or presented to
      court biased, with factors hidden, such as links to industry. Are individual
      evaluations conducted with biased science serving to justify partial conclusions?
      The dangers of powerful influences on the construction of law are highlighted,
      for example, related to the individual complainant malingering and the insurance
      industry protecting its financial interests at the expense of genuinely injured
      patients. In conclusion, suggestions for empirical research are offered.

PMID- 20045195
TI  - Strategic environmental noise mapping: methodological issues concerning the
      implementation of the EU Environmental Noise Directive and their policy
      implications.
AB  - This paper explores methodological issues and policy implications concerning the
      implementation of the EU Environmental Noise Directive (END) across Member
      States. Methodologically, the paper focuses on two key thematic issues relevant
      to the Directive: (1) calculation methods and (2) mapping methods. For (1), the
      paper focuses, in particular, on how differing calculation methods influence
      noise prediction results as well as the value of the EU noise indicator L(den)
      and its associated implications for comparability of noise data across EU states.
      With regard to (2), emphasis is placed on identifying the issues affecting
      strategic noise mapping, estimating population exposure, noise action planning
      and dissemination of noise mapping results to the general public. The implication
      of these issues for future environmental noise policy is also examined.

PMID- 20045196
TI  - Absence of weight gain association with the HTR2C -759C/T polymorphism in
      patients with schizophrenia treated with iloperidone.
AB  - Weight gain is a common side effect of antipsychotics, contributing to poor
      treatment adherence, and previously linked to the -759C/T polymorphism near the
      serotonin receptor 2C gene. The effect of this polymorphism was analyzed in
      schizophrenia patients treated with iloperidone for up to 7 months. No
      association was detected with the modest weight changes observed in these
      patients.

PMID- 20045197
TI  - Climatic relationships with specific clinical subtypes of depression.
AB  - Studies on the relationship between climate and unipolar depression rates have
      yielded mixed results, which could be attributed to the inclusion of
      heterogeneous clinical samples and the use of admission rather than onset dates.
      This study aimed to overcome these methodological issues. During an 8-year
      timeframe, onset rates of unipolar depressive episodes requiring hospitalization
      from individuals living up to 15 km from a selected meteorological station were
      stratified by clinical subtypes and modeled as Autoregressive Integrated Moving
      Average (ARIMA) functions of orthogonal climatic factors obtained by Principal
      Components Analysis (PCA). For comparison purposes, onset rates stratified by
      demographic factors and by diagnosis of Seasonal Affective Disorder (SAD) and
      admission rates were also modeled. The main findings were a negative 1-month
      delayed relationship between onset rates of episodes with melancholic features
      and a climatic factor mainly composed of ambient temperature/sunlight, and a
      negative 1-month delayed relationship between onset rates of episodes with
      psychotic features and a climatic factor mainly composed of barometric pressure.
      Results of this study support a climatic-rather than seasonal-influence in
      specific subtypes of depression. If replicated, they may have nosological and
      therapeutic implications.

PMID- 20045198
TI  - Double dissociation between cognitive and affective empathy in borderline
      personality disorder.
AB  - We sought to characterize the cognitive and affective empathic abilities of
      patients with borderline personality disorder (BPD). While controls showed higher
      cognitive as compared with affective empathy scores, the BPD group demonstrated
      the opposite pattern. These results suggest that a dysfunctional pattern of
      empathic capacity may account for behavioral difficulties in BPD.

PMID- 20045199
TI  - Ulcerative tracheitis among intubated neonates--a clinicopathologic study.
AB  - OBJECTIVE: To determine frequency of ulcerative tracheitis (UT) among intubated
      neonates and identify groups of neonates at greater risk of UT. METHODS: Medical
      histories and autopsy findings from 232 neonates between 1995 and 2006 were
      reviewed retrospectively. All neonates were treated at the Department of
      Neonatology, Clinical Hospital Center Split. Autopsies and histological
      examinations were performed at the Clinical Department of Pathology, Forensic
      Medicine and Cytology. Neonates were classified into groups based on their sex,
      gestational age, survival time and cause of death, duration and reasons for
      intubation. Simplified Wigglesworth classification was used to determine cause of
      death. Chi-squared test and multiple logistical regression analysis were used for
      statistical analysis. RESULTS: UT was found in 44 cases (18.96%). The main risk
      factor for UT development was duration of intubation, especially if it lasted
      over 96 h (P=0.005). Higher frequency of UT was noted in neonates with
      gestational age over 37 weeks (P=0.002) and birth weight over 2500 g (P=0.115).
      CONCLUSION: Our study has shown that the main risk factor for UT development was
      intubation duration exceeding 96 h. Term-borns, and neonates with normal birth
      weight both have higher risk of UT. High risk groups should be observed carefully
      and alternative respiratory support treatment, such as continues positive airway
      pressure (CPAP) may be considered.

PMID- 20045200
TI  - Neuroprotection, regeneration and immunomodulation: broadening the therapeutic
      repertoire in multiple sclerosis.
AB  - Multiple sclerosis (MS), an incurable but manageable disorder, is characterized
      by chronic inflammatory demyelination and neurodegeneration in the central
      nervous system. Although the primary cause of this often devastating disease
      remains elusive, major therapeutic advances have occurred during the past two
      decades. Here, we present a review of current immunomodulatory treatments and
      outline upcoming therapy approaches, including biologics and oral alternatives
      that might have equivalent or superior efficacy and/or enhanced tolerability
      compared with available treatments, and discuss the scientific rationale and
      expected benefits and risks for these compounds. We also speculate about
      alternatives beyond immune-directed approaches, review novel insights into the
      neurobiological consequences of sustained brain inflammation and evaluate future
      perspectives for neuroprotective and neuroregenerative treatment strategies for
      MS.

PMID- 20045201
TI  - Sensory neural codes using multiplexed temporal scales.
AB  - Determining how neuronal activity represents sensory information is central for
      understanding perception. Recent work shows that neural responses at different
      timescales can encode different stimulus attributes, resulting in a temporal
      multiplexing of sensory information. Multiplexing increases the encoding capacity
      of neural responses, enables disambiguation of stimuli that cannot be
      discriminated at a single response timescale, and makes sensory representations
      stable to the presence of variability in the sensory world. Thus, as we discuss
      here, temporal multiplexing could be a key strategy used by the brain to form an
      information-rich and stable representation of the environment.

PMID- 20045202
TI  - Short-term metallothionein inductions in the edible cockle Cerastoderma edule
      after cadmium or mercury exposure: discrepancy between mRNA and protein
      responses.
AB  - Metallothioneins (MT) are essential metal binding proteins involved in metal
      homeostasis and detoxification in living organisms. Numerous studies have focused
      on MT response to metal exposure and showed an important variability according to
      species, metal, concentration and time of exposure. In this study, the expression
      of one isoform of MT gene (Cemt1) and associated MT protein synthesis were
      determined after 1, 3, 9, 24, 72 and 168h of cadmium (Cd) or mercury (Hg)
      exposures in gills of the cockle Cerastoderma edule. This experiment, carried out
      in laboratory conditions, revealed that in Cd-exposed cockles, induction of Cemt1
      is time-dependent following a "pulse-scheme" with significant upregulation at 24h
      and 168h intersected by time point (72h) with significant downregulation. MT
      protein concentration increases with time in gills of exposed cockles in relation
      with the progressive accumulation of Cd in soluble fraction. On contrary, Hg
      exposure does not lead to any induction of Cemt1 mRNA expression or MT protein
      synthesis compared to control, despite a higher accumulation of this metal in
      gills of cockles compared to Cd. The localization of Hg (85-90%) is in insoluble
      fraction, whereas MT was located in the cytoplasm of cells. This gives us a first
      clue to understand the inability of Hg to activate MT synthesis. However, other
      biochemical processes probably occur in gills of C. edule since the remaining
      soluble fraction of Hg exceeds MT sequestration ability. Finally, since one of
      the first main targets of metal toxicity in cells was the mitochondria, some
      genes involved in mitochondria metabolism were also analyzed in order to assess
      potential differences in cellular damages between two metal exposures. Indeed,
      until T(168), no impact on mitochondrial genes was shown following Hg exposure,
      despite the complete lack of MT response. This result indicated the presence of
      other effective cellular ligands which sequester the cytosolic fraction of this
      metal and consequently inhibit metal reactivity. Such competition mechanisms with
      other cytosolic ligands more sensitive to Hg were particularly argued in the
      discussion.

PMID- 20045203
TI  - The unexpected sources of organotin contamination in aquatic toxicological
      laboratory studies.
AB  - Unaccounted sources of contamination can be problematic in toxicological studies
      and can range from the presence of impurities, breakdown products or isoforms of
      the parent compound to the unexpected compounds leaching from dosing apparatus.
      As these compounds are not being tested, they may not be measured in the dosed
      aquaria and hence go undetected, potentially contributing as confounding factors
      in toxicological assessments. In this paper we report the unexpected detection of
      butyltin compounds (mono, di and tributyltin) in flow-through aquaria waters of
      an aquatic toxicological set-up. High and variable leaching rates for dibutyltin
      of 2.0 and 6.6 microg/h were detected during the first week of each of two
      separate flow-through studies. Following this initial 'surge' of dibutyltin
      leachate, a decrease in leachate rate was seen with values of 0.9 and 1.2
      microg/h by Day 14 (second week of study). The main source of the butyltin
      leachates was shown, to be the airline tubing used in the assembly of the air
      supply into each flow-through tank. A 24h period of incubation of the airline
      tubing with clean water led to the leaching of concentrations of 63.8 ng/l TBT
      Sn, 1638.8 ng/l DBT-Sn and 4054.6 ng/l MBT-Sn. The concentration of tributyltin
      detected was within its toxicologically effective range and as such could have
      potentially confounding effects on the toxicological bioassays being used. These
      accidental findings could be of enormous relevance to aquatic toxicologists and
      have an important bearing on the choice of materials used to construct
      experimental exposure aquaria.

PMID- 20045204
TI  - Effects of Alexandrium minutum exposure upon physiological and hematological
      variables of diploid and triploid oysters, Crassostrea gigas.
AB  - The effects of an artificial bloom of the toxin-producing dinoflagellate,
      Alexandrium minutum, upon physiological parameters of the Pacific oyster,
      Crassostrea gigas, were assessed. Diploid and triploid oysters were exposed to
      cultured A. minutum and compared to control diploid and triploid oysters fed T.
      Isochrysis. Experiments were repeated twice, in April and mid-May 2007, to
      investigate effects of maturation stage on oyster responses to A. minutum
      exposure. Oyster maturation stage, Paralytic Shellfish Toxin (PST) accumulation,
      as well as several digestive gland and hematological variables, were assessed at
      the ends of the exposures. In both experiments, triploid oysters accumulated more
      PSTs (approximately twice) than diploid oysters. Significant differences, in
      terms of phenoloxidase activity (PO) and reactive oxygen species (ROS) production
      of hemocytes, were observed between A. minutum-exposed and non-exposed oysters.
      PO in hemocytes was lower in oysters exposed to A. minutum than in control
      oysters in an early maturation stage (diploids and triploids in April experiment
      and triploids in May experiment), but this contrast was reversed in ripe oysters
      (diploids in May experiment). In the April experiment, granulocytes of oysters
      exposed to A. minutum produced more ROS than those of control oysters; however,
      in the May experiment, ROS production of granulocytes was lower in A. minutum
      exposed oysters. Moreover, significant decreases in free fatty acid,
      monoacylglycerol, and diacylglycerol contents in digestive glands of oysters
      exposed to A. minutum were observed. Concurrently, the ratio of reserve lipids
      (triacylglycerol, ether glycerides and sterol esters) to structural lipids
      (sterols) decreased upon A. minutum exposure in both experiments. Also, several
      physiological responses to A. minutum exposure appeared to be modulated by
      maturation stage as well as ploidy of the oysters.

PMID- 20045205
TI  - Participation of metropolitan, urban and rural community-dwelling older adults.
AB  - Environmental factors are important in maintaining a high level of participation.
      This cross-sectional study aimed at comparing the level of participation of older
      adults living in rural, urban and metropolitan environments and exploring
      sociodemographic factors associated with participation according to each type of
      environment. A total of 350 community-dwelling participants showing a normal
      aging process were randomly recruited. Participation in daily activities and
      social roles was measured with the Assessment of Life Habits. Sociodemographic
      and environmental data were gathered using a questionnaire. Participants from the
      rural region reported less schooling, a lower income, no access to public
      transportation and less access to stores than others. Participants from the
      metropolitan region differed in terms of less use of a car, less satisfaction
      with their social support and feeling less secure in their neighborhood. However,
      no significant difference was found between the metropolitan, urban and rural
      groups for participation in daily activities and social roles. Furthermore, the
      variables most associated with participation were similar for all three regions.
      This suggests that although the environment of older adults living in
      metropolitan, urban and rural region differs, their level of engagement in daily
      activities and social roles is similar.

PMID- 20045206
TI  - Acute myocardial infarction without significant coronary stenoses associated with
      endogenous subclinical hyperthyroidism.
AB  - Subclinical hyperthyroidism is an increasingly recognized entity that is defined
      as a normal serum free thyroxine and free triiodothyronine levels with a thyroid
      stimulating hormone level suppressed below the normal range and usually
      undetectable. It has been reported that subclinical hyperthyroidism is not
      associated with coronary heart disease or mortality from cardiovascular causes
      but it is sufficient to induce arrhythmias including atrial fibrillation and
      atrial flutter. Nowadays, there is growing interest regarding endogenous
      sublinical hyperthyroidism and the cardiovascular system. We present a case of
      acute myocardial infarction without significant coronary stenoses in a 75-year
      old Italian woman with endogenous subclinical hyperthyroidism. Also this case
      focuses attention on the importance of a correct evaluation of endogenous
      subclinical hyperthyroidism.

PMID- 20045207
TI  - Common polymorphism +45T/G in adiponectin gene as potential modulator of in-stent
      restenosis development.
AB  - Adiponectin has been reported previously to be associated with in-stent
      restenosis (ISR) after percutaneous coronary intervention (PCI). This paper
      discusses possible associations between ISR after PCI and the +45T/G polymorphism
      in the adiponectin locus.

PMID- 20045208
TI  - Wet BNP, fluid and hemodynamic status at discharge in acute heart failure.
AB  - We comment the noteworthy results of Pimenta et al. concerning the significance
      of discharge BNP levels in acute HF patients. The innovation of Pimento's study
      is the systematic research of the potential relationship between BNP and clinical
      and hemodynamic parameters. We focused the attention on the importance of wet
      "BNP" in managing HF and its ability to reflect congestion and multiple
      underlying patho-physiological disturbances. The first observation, regarding the
      statistical order, underlines the importance of renal insufficiency at discharge
      in genesis of higher BNP levels. Secondly, we note that the relationship between
      natriuretic peptides and the non-invasive measurement of the fluid status
      assessed by bioelectrical impedance analysis was already demonstrated. Thirdly,
      we comment on the potential therapeutical implication of the verified
      relationship between BNP and albumin levels and we argue on the clinical utility
      of the albumin supplementation or hypertonic solutions in unstable HF management
      due to their oncotic power. Fourthly, we wish to further examine the role of
      central volemia. We underline that some studies had demonstrated that systemic
      congestion may be a mirror of central congestion and may also influence these
      levels alone in acute and also chronic HF patients. We believe that a concealed
      or poorly-assessed accumulation of systemic fluid is of crucial importance in
      managing HF, which frequently remains undiagnosed or inappropriately treated,
      thus requiring recurrent hospital readmission and disease progression.
      Furthermore not only BNP at discharge but also bioimpedance detection may be
      helpful to discover misdiagnosed congestion. We are of the opinion that, in cases
      of hospitalized HF and thereafter in ambulatory setting, the achievement and,
      then, maintenance of dry-wet tailoring diuretics, fluid and sodium intake is the
      key approach leading to a euvolemic status, a lowering of the NYHA class and an
      improvement in cardiac hemodynamics. All of these factors are conducive to
      lowered BNP plasma levels.

PMID- 20045209
TI  - When studies with positive-sounding acronyms turned out to be negative trials.

PMID- 20045211
TI  - Efficacy of supercritical carbon dioxide for nonthermal inactivation of
      Escherichia coli K12 in apple cider.
AB  - This study evaluated the efficacy of a supercritical carbon dioxide (SCCO(2))
      system with a gas-liquid porous metal contactor for eliminating Escherichia coli
      K12 in apple cider. Pasteurized, preservative-free apple cider was inoculated
      with E. coli K12 and processed using the SCCO(2) system at CO(2) concentrations
      of 0-10% (wt.%, g CO(2)/100g product), outlet temperatures of 34, 38, and 42
      degrees C, a system pressure of 7.6 MPa, and a flow rate of 1L/min. Increased
      CO(2) concentrations and temperatures significantly (P<0.05) enhanced the
      bactericidal effect, resulting in a maximum reduction of 7.31 log CFU/mL at 8%
      CO(2) and 42 degrees C. A response surface model indicated that minimum CO(2)
      concentrations of 9.9% at 34 degrees C, 7.4% at 38 degrees C, and 5.4% at 42
      degrees C are needed to achieve a 5-log reduction of E. coli K12 in apple cider.
      SEM observations showed morphological changes in the cell envelope after SCCO(2)
      processing. At a processing condition of 8% and 38 degrees C, the reduction of E.
      coli was 6.03 log and the sublethal injury of the survivors was 84%. The regrowth
      or survival of E. coli in SCCO(2) processed apple cider was not observed during
      storage for 28 days at 4, 8, and 20 degrees C. Thus this study showed the
      potential of SCCO(2) processing with a gas-liquid porous metal contactor for the
      nonthermal pasteurization of apple cider.

PMID- 20045212
TI  - From yesterday to tomorrow: making a difference to global diabetes.

PMID- 20045210
TI  - Musculoskeletal molecular imaging: a comprehensive overview.
AB  - Molecular imaging permits non-invasive visualization and measurement of molecular
      and cell biology in living subjects, thereby complementing conventional
      anatomical imaging. Herein, we review the emerging application of molecular
      imaging for the study of musculoskeletal biology. Utilizing mainly
      bioluminescence and fluorescence techniques, molecular imaging has enabled in
      vivo studies of (i) the activity of osteoblasts, osteoclasts, and hormones, (ii)
      the mechanisms of pathological cartilage and bone destruction, (iii) skeletal
      gene and cell therapy with and without biomaterial support, and (iv) the cellular
      processes in osteolysis and osteomyelitis. In these applications, musculoskeletal
      molecular imaging demonstrated feasibility for research in a myriad of
      musculoskeletal conditions ranging from bone fracture and arthritis to skeletal
      cancer. Importantly, these advances herald great potential for innovative
      clinical imaging in orthopedics, rheumatology, and oncology.

PMID- 20045213
TI  - Effects of Glimepiride on metabolic parameters and cardiovascular risk factors in
      patients with newly diagnosed type 2 diabetes mellitus.
AB  - BACKGROUND: To investigate the effects of Glimepiride on blood glucose in
      patients with newly diagnosed type 2 diabetes mellitus (T2DM) in connection with
      plasma lipoproteins and plasminogen activity. METHODS: A total of 565 T2DM
      patients were received Glimepiride (n=333) or Glibenclamide (n=232) for 12 weeks.
      We observed the level of blood glucose (BG), glycated hemoglobin (HbA1C), the
      insulin resistance (IR) state, plasma lipoproteins, tissue-type plasminogen
      activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) before and
      after a 12 weeks of treatment. RESULTS: After 12 weeks with Glimepiride
      treatment, significant reductions were observed in fasting blood glucose (FBG)
      and 2-h postprandial BG(PBG), HbA1C (from 8.60+/-3.10 to 7.10+/-1.60%) and HOMA
      IR (from 4.11+/-0.85 to 2.42+/-0.91%). The level of total cholesterol (TC),
      triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were
      significantly decreased, whereas that of high-density lipoprotein (HDL) was
      increased markedly with statistical significance. In addition, there was an
      obvious improvement in t-PA activity (from 0.225+/-0.11 to 0.457+/-0.177IU/ml);
      whereas the PAI-1 activity was decreased significantly (from 0.898+/-0.168 to
      0.533+/-0.215AU/ml). No significant changes were observed in plasma lipoprotein
      profiles and plasminogen activity in Glibenclamide receiving group. CONCLUSIONS:
      Glimepiride can rapidly and stably improve glycemic control and lipoprotein
      metabolism, significantly alleviate insulin resistance and enhance fibrinolytic
      activity.

PMID- 20045214
TI  - A convenient synthesis of nucleoside diphosphate glycopyranoses and other
      polyphosphorylated bioconjugates.
AB  - In this review, we summarize results obtained using a conceptionally new chemical
      synthesis of NDP-sugars based on cycloSaligenyl (cycloSal) nucleotides as
      starting material (cycloSal technique). The cycloSal technique not only leads to
      stereoisomerically defined NDP-sugars in high yield, but the same principle
      provides very efficient routes towards nucleoside di- and -triphosphates.
      Moreover, sugar-nucleotides such as CMP-Neu5Ac and dinucleoside polyphosphates
      are available. Thus, the method offers a nearly universal chemical access towards
      a large number of highly interesting bioconjugates and biomolecules.

PMID- 20045215
TI  - Simultaneous isolation of intact mitochondria and chloroplasts from a single
      pulping of plant tissue.
AB  - Isolated organelles are suitable tools for the investigation of organelle
      function. However, if the properties of different organelles are to be compared,
      analysis is generally impeded by the fact that the organelles are isolated
      independently from each other from different specimens, different tissues or even
      different plants, i.e. the organelles have been exposed to different conditions
      during growth and development. Here we describe a method to isolate intact
      chloroplasts and mitochondria simultaneously from a single pulping of pea leaves,
      which results in organelles with an essentially identical physiological
      background. The functionality of the isolated chloroplasts and mitochondria is
      demonstrated by protein transport experiments, which yield results identical to
      those obtained with independently isolated organelles. With slight modifications,
      the method is also successfully applied to organelles from potato and spinach,
      which implies that it may be generally applicable to organelles from many
      different species.

PMID- 20045216
TI  - Neurosteroid biosynthetic pathways changes in prefrontal cortex in Alzheimer's
      disease.
AB  - Expression of the genes for enzymes involved in neurosteroid biosynthesis was
      studied in human prefrontal cortex (PFC) in the course of Alzheimer's disease
      (AD) (n=49). Quantitative RT-PCR (qPCR) revealed that mRNA levels of diazepam
      binding inhibitor (DBI), which is involved in the first step of steroidogenesis
      and in GABAergic transmission, were increased, as were mRNA levels for several
      neurosteroid biosynthetic enzymes. Aromatase, 17beta-hydroxysteroid dehydrogenase
      type 1 (HSD17B1) and aldo-keto reductase 1C2 (AKR1C2), were all increased in the
      late stages of AD. Several GABA-A subunits were significantly reduced in AD.
      Increased expression of aromatase in the PFC was confirmed by
      immunohistochemistry and was found to be localized predominantly in astrocytes.
      These data suggest a role for estrogens and allopregnanolone produced by
      astrocytes in the PFC in AD, possibly as part of a rescue program. The reduced
      gene expression of some synaptic and extra-synaptic GABA-A subunits may indicate
      a deficit of modulation of GABA-A receptors by neuroactive steroids, which may
      contribute to the neuropsychiatric characteristics of this disease.

PMID- 20045217
TI  - Metabolic syndrome, mild cognitive impairment, and progression to dementia. The
      Italian Longitudinal Study on Aging.
AB  - We investigated the relationship of metabolic syndrome (MetS) and its individual
      components with incidence of mild cognitive impairment (MCI) and its progression
      to dementia in a large longitudinal Italian population-based sample with a 3.5
      year follow-up. A total of 2097 participants from a sample of 5632 65-84-year-old
      subjects from the Italian Longitudinal Study on Aging were evaluated. MetS was
      defined according to the Third Adults Treatment Panel of the National Cholesterol
      Education Program criteria. MCI, dementia, Alzheimer's disease (AD), and vascular
      dementia (VaD) were classified using current published criteria. Among MCI
      patients those with MetS (N=49) had a higher risk of progression to dementia (HR,
      4.40; 95% CI, 1.30-14.82) compared with those without MetS (N=72). After a
      multivariate adjustment, the risk in MCI patients with MetS approximately doubled
      (multivariate adjusted HR, 7.80, 95% CI 1.29-47.20) compared with those MCI
      without MetS. Finally, among non-cognitively impaired individuals there were no
      significant differences in risks of developing MCI in those who were affected by
      MetS (N=608) in comparison with those without MetS (N=837), as well as excluding
      those individuals with undernutrition or low inflammatory status with or without
      undernutrition. In our population, among MCI patients the presence of MetS
      independently predicted an increased risk of progression to dementia over 3.5
      years of follow-up.

PMID- 20045218
TI  - Age-related alterations affect the susceptibility of mice to prion infection.
AB  - The sporadic and familial forms of Creutzfeldt-Jacob disease (sCJD and fCJD)
      usually appear at older ages (60-70 years and ~ 50, respectively). Nevertheless,
      infectious forms such as Kuru and variant CJD (vCJD) present mostly at a much
      earlier age. To study the effect of age on the pathogenesis of infectious prion
      disease, we inoculated young and aged mice intraperitoneally with RML prions,
      followed them to disease end point and studied their disease characteristics. We
      now show that mice infected at older age present a significantly longer
      incubation time then mice infected at young age. Additionally, brains of mice
      infected at older age present significantly less disease-specific pathological
      markers such as gliosis, vacuolation and PrP(Sc) accumulation. Concomitantly,
      gene expression analysis revealed that the upregulation of disease-associated
      inflammatory and stress-response genes, was significantly less pronounced in the
      brains of mice infected at older age. Based on this data, we suggest that
      alterations associated with aging, are accountable for the delay in the disease
      onset and the milder pathology in prion-infected aged mice.

PMID- 20045219
TI  - [Three years of the smoking prevention law in Spain: the good and bad aspects].

PMID- 20045220
TI  - Synthesis of tropolone derivatives and evaluation of their in vitro
      neuroprotective activity.
AB  - beta-Thujaplicin (hinokitiol or 2-hydroxy-4-isopropyl-2,4,6-cycloheptatrien-1
      one), a natural tropolone, shows numerous activities while its synthetic
      analogues were found to exhibit anticancer and anti-ischemic activity. However,
      the ability of tropolone derivatives to protect neuronal cells from oxidative
      stress-induced cell damage has not been studied so far. As an ongoing effort
      toward highly effective antioxidants with potential neuroprotective activity, we
      have synthesized 7-substituted derivatives of beta-thujaplicin and its methoxy
      analogue. The substituents were heterocycles (piperazine, morpholine) or
      heteroaromatics (triazoles, pyridine). Only the piperazine derivatives of beta
      thujaplicin were able to protect HT22 hippocampal neurons from oxidative stress
      induced cell death.

PMID- 20045221
TI  - Synthesis of new spiroindolinones incorporating a benzothiazole moiety as
      antioxidant agents.
AB  - 3H-Spiro[1,3-benzothiazole-2,3'-indol]-2'(1'H)-ones 3a-c and 4a-e were
      synthesized from treating the 5-substituted 1H-indole-2,3-diones with 2
      aminothiophenol in ethanol. The structures were confirmed by elemental analyses,
      spectrometry (IR, (1)H NMR, (13)C NMR, HSQC-2D and LCMS-APCI) and single crystal
      X-ray analysis. The new compounds were screened for their antioxidant activities
      such as the Fe(3+)/ascorbate system induced inhibition of lipid peroxidation (LP)
      in liposomes, trolox equivalent antioxidant capacity (TEAC), scavenging effect on
      diphenylpicryl hydrazine (DPPH*), and reducing power. These compounds showed
      potent scavenging activities against DPPH* and 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulphonic acid) (ABTS*(+)) radicals, reducing powers, and
      strong inhibitory capacity on lipid peroxidation. Compound 4a incorporating
      methyl both at R(1) and R(2) was found to be the most potent antioxidant
      described in this study. Compounds 3b and 4b were selected as representative
      compounds by the National Cancer Institute for screening against anticancer
      activity and these compounds were found to be cytotoxic against CNS cancer cell
      line SNB-75 in the primary screen.

PMID- 20045222
TI  - Design, synthesis, and biological evaluation of novel pyrimidine derivatives as
      CDK2 inhibitors.
AB  - Novel derivatives of 2,4,5,6-tetrasubstituted pyrimidine cyclin-dependent kinase
      (CDK2) inhibitors was designed and synthesized. We built a library of proposed
      pyrimidine derivatives and by using pharmacophore and docking techniques we made
      our selections. We modified the proposed compounds due to the interaction of
      docked structures with the protein to achieve the best fit. The newly synthesized
      compounds showed potent and selective CDK2 inhibitory activities and inhibited in
      vitro cellular proliferation in cultured human tumor cells. The design, synthesis
      and biological evaluation of these 2,4,5,6-tetrasubstituted pyrimidine
      derivatives are reported.

PMID- 20045223
TI  - Synthesis and evaluation of the alpha-glucosidase inhibitory activity of 3-[4
      (phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives.
AB  - In the course of studies directed toward the discovery of novel non-sugar alpha
      glucosidase inhibitors for the treatment of diabetes, a series of 3-[4
      (phenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one derivatives was synthesized and
      evaluated as alpha-glucosidase inhibitors. Most compounds showed good inhibitory
      activity with IC(50) values ranging from 0.0645 microM to 26.746 microM. 7
      Hydroxy-6-methoxy-3-[4-(4-methylphenylsulfonamido)benzoyl]-2H-1-benzopyran-2-one
      7u manifested the most potent inhibitory activity with an IC(50) value of 0.0645
      microM.

PMID- 20045224
TI  - 6-Substituted 2-(N-trifluoroacetylamino)imidazopyridines induce cell cycle arrest
      and apoptosis in SK-LU-1 human cancer cell line.
AB  - A series of 6-substituted 2-(N-trifluoroacetylamino)imidazopyridines have been
      synthesized and their bioactivities were evaluated. Compounds 6a, 6c, and 11a
      were the most active compounds with modest cytotoxic activity against six human
      cancer cell lines U251 (glioma), PC-3 (prostate), K-562 (leukemia), HCT-15
      (colon), MCF7 (breast) and SK-LU-1 (lung). The cell cycle analysis showed that
      compounds 6a, 6c, and 11a induce a G2/M phase cell cycle arrest on SK-LU-1 cell
      line where inhibition of CDK-1 and CDK-2 may be implicated.

PMID- 20045225
TI  - [Positive Pneumocystis jirovecii PCR in immunocompromised patients with a
      systemic disease: infection or colonisation?].
AB  - PURPOSE: Pneumocystis pneumonia is a serious opportunistic infection that
      frequently occurred in HIV-seropositive patients, prior to the advent of highly
      active antiretroviral therapy. This infection can also occur in patients with
      systemic diseases. The diagnostic value of a positive Pneumocystis jirovecii PCR
      in patients with systemic diseases has not yet been clearly defined. METHODS: We
      conducted a retrospective study of patients with a systemic disease who presented
      clinical symptoms consistent with Pneumocystis pneumonia to assess the diagnostic
      value of a positive P. jirovecii PCR in respiratory samples. RESULTS: During a 10
      year period, 73 patients with respiratory symptoms underwent respiratory sampling
      with tests for the presence of P. jirovecii. P. jirovecii PCR was positive in 20
      patients: Pneumocystis pneumonia was diagnosed in nine patients and for six of
      these nine patients, the microscopic examination was negative. Patients with
      Pneumocystis pneumonia differed from those who were solely colonized in that they
      had a lower CD4+ T lymphocyte count, were more likely to have received
      immunosuppressive treatment, and were not receiving primary prophylaxis against
      Pneumocystis pneumonia. Chronic pulmonary involvement was more frequent among
      colonized patients. CONCLUSION: A positive P. jirovecii PCR does not always
      indicate overt infection. However, in a context of severe immunosuppression and
      in the absence of prophylaxis against Pneumocystis pneumonia, a specific
      treatment should be considered.

PMID- 20045226
TI  - [Budd-Chiari syndrome associated with celiac disease].
AB  - The association of Budd-Chiari syndrome and celiac disease is rare and has been
      reported in only 13 cases. We report a 23-year-old man with celiac disease,
      treated with gluten-free diet since the age of 16 years. He presented with
      epigastric pain that was secondary to a Budd-Chiari syndrome. No other cause than
      celiac disease could be identified.

PMID- 20045227
TI  - Identifying priorities for establishing bilingual provision in nurse education: a
      scoping study.
AB  - Research evidence demonstrates that offering language choice to patients enhances
      the quality of healthcare provision. This has implications for the preparation of
      nurses for practice in bilingual settings, where legislation often leads to
      demands for health services in both languages and bilingual competence amongst
      healthcare providers. This paper reports on a scoping study of bilingual
      provision in nurse education in the bilingual context of Wales, UK, as a means of
      informing the evidence base for national strategic planning. The study
      incorporated three elements: (i) literature analysis (ii) policy review and (iii)
      stakeholder consultation (n=70). Six themes emerged from the stakeholder
      consultation, reflecting the main drivers and barriers associated with bilingual
      provision in course delivery. These themes aligned with findings identified from
      the policy and literature review that related to strategic, organisational and
      individual influences on bilingual educational provision. Strategic planning for
      bilingual provision in nurse education in Wales should take account of the
      factors that affect provision at different levels. These factors feature across
      bilingual settings outside the UK, thus giving the study international relevance
      and scope to inform the delivery of nurse education that meets the needs of wider
      diverse language communities.

PMID- 20045228
TI  - An exploratory study of the application of biosciences in practice, and
      implications for pre-qualifying education.
AB  - Reinforcement of learning in practice may help students learn bioscience but is
      contingent on adequate support from staff nurses. A 'snapshot' of the situation
      in practice was obtained (2006/7), with context from lecturers. In Stage 1,
      surgical care nurses were presented with scenarios and interviewed. Responses
      were located within proficiency standards. Further responses related to
      application of 'Early Warning System' (EWS) tools on the wards. In Stage 2, a
      questionnaire was sent to lead bioscience lecturers at English universities.
      Nurses identified widespread knowledge of clinical observations. Underlying
      factors were variably articulated, and was not correlated with years in practice
      or first qualification. Experience was considered most important to learning
      bioscience but most nurses self-rated their bioscience knowledge as weak.
      Lecturers anticipated bioscience understanding at registration to be equivalent
      to around 'A' level standard, yet most thought the actual standard was lower. EWS
      tools were considered useful by nurses and lecturers, but potentially de
      skilling. A dichotomy in expectation and reality of bioscience learning persists.
      The learning environment in practice is hindered either by practitioners having
      poor understanding, or low confidence in what they know. Post-qualifying
      education will help resolve recognised difficulties in student learning of
      biosciences, though EWS tools may not encourage deeper learning.

PMID- 20045229
TI  - Removal of uranium(VI) from aqueous solutions and nuclear industry effluents
      using humic acid-immobilized zirconium-pillared clay.
AB  - Removal of uranium [U(VI)] from aqueous solutions with humic acid-immobilized
      zirconium-pillared clay (HA-Zr-PILC) was investigated using a batch adsorption
      technique. The adsorbent was characterized using XRD, FTIR, SEM, TG/DTG, surface
      area analyzer and potentiometric titration. The effects of pH, contact time,
      initial concentration, adsorbent dose, and adsorption isotherm on the removal
      process were evaluated. A maximum removal of 97.6+/-2.1 and 94.7+/-3.3% was
      observed for an initial concentration of 50 and 100 mg L(-1), respectively at pH
      6.0 and an adsorbent dose of 2.0 g L(-1). Equilibrium was achieved in
      approximately 180 min. The mechanism for the removal of U(VI) ions by HA-Zr-PILC
      was based on an ion exchange reaction. The experimental kinetic and isotherm data
      were analyzed using a second-order kinetic equation and Langmuir isotherm model,
      respectively. The monolayer adsorption capacity for U(VI) removal was found to be
      132.68+/-5.04 mg g(-1). An increase of temperature of the medium caused an
      increase in metal adsorption. Complete removal (approximately = 100%) of U(VI)
      from 1.0 L of a simulated nuclear industry effluent sample containing 10.0 mg
      U(VI) ions was possible with 1.5 g of HA-Zr-PILC. The adsorbent was suitable for
      repeated use (over 4 cycles) without any noticeable loss of capacity.

PMID- 20045230
TI  - Biopsy examination of squamous cell carcinoma of the tongue: source of
      significant prognostic information?
AB  - Histological analysis of tumour resection for squamous cell carcinoma (SCC) of
      the tongue yields prognostic information. We analysed histological slides of
      biopsy and tumour resection specimens using an adapted malignancy grading score
      and analysed variables of neck dissections. There was moderate correlation
      between biopsy and tumour resection using malignancy grading scores (correlation
      coefficient 0.45); good agreement of tumour grade (79%), tumour depth (76%), and
      type of invasive front (80%), but correlation was only fair to moderate
      (kappa=0.38, kappa=0.51, and kappa=0.41, respectively). Correlation of the biopsy
      grading score and invaded nodes in the neck, extra capsular spread, and soft
      tissue disease was not significant.

PMID- 20045231
TI  - A systematic review of patient self-completed questionnaires suitable for oral
      and maxillofacial surgery.
AB  - Patient reported outcomes (PRO) have an established role when reporting treatment
      outcomes. This data is usually collected using patient self-completed
      questionnaires. There are numerous questionnaires available and selecting the
      most appropriate one can be difficult. AIM: The aim of this article was to carry
      out a systematic review of the literature to identify publications using patient
      self-completed questionnaires suitable for oral and maxillofacial surgery. The
      questionnaires were collated and grouped according to sub-speciality interests.
      METHOD: The ISI search engine with cross-reference using Pub Med and Ovid was
      searched for publications between 1981 and March 2009. Abstracts written in
      English were reviewed by two of the authors independently. RESULTS: A total of
      511 abstracts were reviewed and the paper cites 56 studies with self-administered
      instruments. The number of subsite specific questionnaires identified were; cleft
      lip and palate (1), craniofacial surgery (2), dentoalveolar surgery (6),
      distraction osteogenesis (1), facial aesthetic surgery (4), facial pain (1), head
      and neck cancer (14), maxillofacial injury (3), oral medicine and oral mucosal
      disorders (2), orthognathic surgery (1), pre-prosthetic surgery and dental
      implants (15), skull base surgery (7), temporomandibular joint (2). CONCLUSION:
      There is a tremendous variety of validated questionnaires available that are
      suitable for oral and maxillofacial surgery. This summary serves as a useful
      reference point when selecting a questionnaire for an audit or research projects.
      It also describes publications, which have used the various questionnaires, thus
      readily identifying papers that might be useful for comparison.

PMID- 20045232
TI  - Squamous cell carcinoma arising in mucosal plasmacytosis.
AB  - The authors present an unusual case of invasive squamous cell carcinoma (SCC)
      developing in a pre-existing plasmacytosis of the lip. The roles of chronic
      inflammation, immunosuppression, and smoking in the pathogenesis of this tumour
      are briefly discussed. The authors highlight a significant side effect of the use
      of immunosuppressive drugs in benign conditions.

PMID- 20045233
TI  - A conceptual framework: redefining forest soil's critical acid loads under a
      changing climate.
AB  - Federal agencies of several nations have or are currently developing guidelines
      for critical forest soil acid loads. These guidelines are used to establish
      regulations designed to maintain atmospheric acid inputs below levels shown to
      damage forests and streams. Traditionally, when the critical soil acid load
      exceeds the amount of acid that the ecosystem can absorb, it is believed to
      potentially impair forest health. The excess over the critical soil acid load is
      termed the exceedance, and the larger the exceedance, the greater the risk of
      ecosystem damage. This definition of critical soil acid load applies to exposure
      of the soil to a single, long-term pollutant (i.e., acidic deposition). However,
      ecosystems can be simultaneously under multiple ecosystem stresses and a single
      critical soil acid load level may not accurately reflect ecosystem health risk
      when subjected to multiple, episodic environmental stress. For example, the
      Appalachian Mountains of western North Carolina receive some of the highest rates
      of acidic deposition in the eastern United States, but these levels are
      considered to be below the critical acid load (CAL) that would cause forest
      damage. However, the area experienced a moderate three-year drought from 1999 to
      2002, and in 2001 red spruce (Picea rubens Sarg.) trees in the area began to die
      in large numbers. The initial survey indicated that the affected trees were
      killed by the southern pine beetle (Dendroctonus frontalis Zimm.). This insect is
      not normally successful at colonizing these tree species because the trees
      produce large amounts of oleoresin that exclude the boring beetles. Subsequent
      investigations revealed that long-term acid deposition may have altered red
      spruce forest structure and function. There is some evidence that elevated acid
      deposition (particularly nitrogen) reduced tree water uptake potential, oleoresin
      production, and caused the trees to become more susceptible to insect
      colonization during the drought period. While the ecosystem was not in exceedance
      of the CAL, long-term nitrogen deposition pre-disposed the forest to other
      ecological stress. In combination, insects, drought, and nitrogen ultimately
      combined to cause the observed forest mortality. If any one of these factors were
      not present, the trees would likely not have died. This paper presents a
      conceptual framework of the ecosystem consequences of these interactions as well
      as limited plot level data to support this concept. Future assessments of the use
      of CAL studies need to account for multiple stress impacts to better understand
      ecosystem response.

PMID- 20045234
TI  - Identification and quantification of a novel nitrate-reducing community in
      sediments of Suquia River basin along a nitrate gradient.
AB  - We evaluated the molecular diversity of narG gene from Suquia River sediments to
      assess the impact of the nitrate concentration and water quality on the
      composition and structure of the nitrate-reducing bacterial community. To this
      aim, a library of one of the six monitoring stations corresponding to the highest
      nitrate concentration was constructed and 118 narG clones were screened.
      Nucleotide sequences were associated to narG gene from alpha-, beta-, delta-,
      gammaproteobacteria and Thermus thermophilus. Remarkably, 18% of clones contained
      narG genes with less than 69% similarity to narG sequences available in
      databases. Thus, indicating the presence of nitrate-reducing bacteria with novel
      narG genes, which were quantified by real-time PCR. Results show a variable
      number of narG copies, ranging from less than 1.0 x 10(2) to 5.0 x 10(4) copies
      per ng of DNA, which were associated with a decreased water quality index
      monitored along the basin at different times.

PMID- 20045235
TI  - Sulfate and glutathione enhanced arsenic accumulation by arsenic hyperaccumulator
      Pteris vittata L.
AB  - This experiment examined the effects of sulfate (S) and reduced glutathione (GSH)
      on arsenic uptake by arsenic hyperaccumulator Pteris vittata after exposing to
      arsenate (0, 15 or 30 mg As L(-1)) with sulfate (6.4, 12.8 or 25.6 mg S L(-1)) or
      GSH (0, 0.4 or 0.8 mM) for 2-wk. Total arsenic, S and GSH concentrations in plant
      biomass and arsenic speciation in the growth media and plant biomass were
      determined. While both S (18-85%) and GSH (77-89%) significantly increased
      arsenic uptake in P. vittata, GSH also increased arsenic translocation by 61-85%
      at 0.4 mM (p < 0.05). Sulfate and GSH did not impact plant biomass or arsenic
      speciation in the media and biomass. The S-induced arsenic accumulation by P.
      vittata was partially attributed to increased plant GSH (21-31%), an important
      non-enzymatic antioxidant countering oxidative stress. This experiment
      demonstrated that S and GSH can effectively enhance arsenic uptake and
      translocation by P. vittata.

PMID- 20045236
TI  - Dynamic modelling of atmospherically-deposited Ni, Cu, Zn, Cd and Pb in Pennine
      catchments (northern England).
AB  - Simulation modelling with CHUM-AM was carried out to investigate the accumulation
      and release of atmospherically-deposited heavy metals (Ni, Cu, Zn, Cd and Pb) in
      six moorland catchments, five with organic-rich soils, one with calcareous brown
      earths, in the Pennine chain of northern England. The model considers two soil
      layers and a third layer of weathering mineral matter, and operates on a yearly
      timestep, driven by deposition scenarios covering the period 1400-2010. The
      principal processes controlling heavy metals are competitive solid-solution
      partitioning of solutes, chemical interactions in solution, and chemical
      weathering. Agreement between observed and simulated soil metal pools and surface
      water concentrations for recent years was generally satisfactory, the results
      confirming that most contemporary soil metal is from atmospheric pollution.
      Metals in catchments with organic-rich soils show some mobility, especially under
      more acid conditions, but the calcareous mineral soils have retained nearly all
      anthropogenic metal inputs. Complexation by dissolved organic matter and co
      transport accounts for up to 80% of the Cu in surface waters.

PMID- 20045238
TI  - Nephrologists' perspectives on the effect of guidelines on clinical practice: a
      semistructured interview study.
AB  - BACKGROUND: A consistent gap exists between evidence-based guideline
      recommendations and clinical practice across all medical disciplines, including
      nephrology. This study aims to explore nephrologists' perspectives on guidelines
      and elicit their perspectives on the effects of guidelines on clinical decisions.
      METHODS: Semistructured face-to-face interviews were undertaken with 19
      nephrologists from a variety of clinical settings across Australia. Participants
      were asked about their views of clinical practice guidelines in nephrology, both
      local (Caring for Australasians With Renal Impairment [CARI]) and international,
      and their opinions of other factors that shape their decision making. Interviews
      were recorded, transcribed, and analyzed qualitatively. RESULTS: 4 major themes
      were identified. First, overall, the nephrologists interviewed trusted the CARI
      guideline process and output. Second, guidelines served a variety of purposes,
      providing a good summary of evidence, a foundation for practice, an educational
      resource, and justification for funding requests to policy makers, as well as
      promoting patient adherence to treatment. Third, guidelines were only one input
      into decision making. Other inputs included individual patient quality of life
      and circumstances, opinion leaders, peers, nephrologists' own experiences, the
      regulation and subsidy framework for drugs and devices, policies and work
      practices of the local unit, and other sources of evidence. Fourth, guideline
      uptake varied. Factors that favored the use of guidelines included having a
      strong evidence base, being current, including specific targets and an explicit
      treatment algorithm, being sent frequent reminders, and having local peer support
      for implementation and the necessary personnel and other resources for effective
      implementation. CONCLUSIONS: Evidence-based guidelines appear to impact strongly
      on clinical decision making of Australian nephrologists, but are only one input.
      Improvements in the evidence that underpins guidelines and improvements in the
      content and formatting of guidelines are likely to make them more influential on
      decision making. Trust in the guideline groups' processes is a prerequisite for
      implementation.

PMID- 20045237
TI  - Prediction of ESRD in pauci-immune necrotizing glomerulonephritis: quantitative
      histomorphometric assessment and serum creatinine.
AB  - BACKGROUND: Clinical and pathologic features that predict outcome have important
      potential application in patients with pauci-immune necrotizing
      glomerulonephritis (usually antineutrophil cytoplasmic antibody-associated
      vasculitis). This study examines the predictive value of simple quantitative
      renal histologic measurements in a large cohort with extended follow-up. STUDY
      DESIGN: Cohort study. SETTING & PARTICIPANTS: 390 consecutive patients with pauci
      immune necrotizing glomerulonephritis at a single hospital (1983-2002); 90
      patients underwent repeated kidney biopsy during follow-up. PREDICTORS: Age and
      serum creatinine concentration at biopsy, antineutrophil cytoplasmic antibody
      specificity, percentage of normal glomeruli, percentage of glomeruli with active
      lesions, and index of chronic damage (quantitative measurement of established
      cortical damage) in the initial kidney biopsy for all patients. The same factors
      were assessed in both biopsy specimens for patients undergoing an additional
      biopsy. OUTCOMES & MEASUREMENTS: End-stage renal disease and patient survival.
      RESULTS: Mortality at 1 and 5 years was 23% and 40%, respectively: standardized
      mortality ratio, 4.74 (95% CI, 3.62-6.32). End-stage renal disease was reached by
      14% and 18% at 1 and 5 years, respectively. In multivariable analysis, serum
      creatinine level at biopsy and percentage of normal glomeruli in the initial
      biopsy specimen were the best predictors of kidney survival. C Statistics were
      0.80 for creatinine level alone and 0.83 for creatinine level with normal
      glomeruli. In patients undergoing an additional biopsy, rapid progression in the
      index of chronic damage and serum creatinine level at the second biopsy were
      associated with kidney survival in multivariable analysis. LIMITATIONS:
      Retrospective analysis. External validity of the index of chronic damage requires
      further assessment. Selection bias may influence repeated biopsy analyses.
      CONCLUSIONS: Serum creatinine level at biopsy best predicts kidney survival in
      patients with pauci-immune necrotizing glomerulonephritis overall.

PMID- 20045239
TI  - Relative deprivation and mortality in South Africa.
AB  - This paper tests the relative income hypothesis by considering the relationship
      between mortality, income and relative deprivation in South Africa using
      individual-level data on income and five measures of relative deprivation each
      with a different reference group. We find that income tends to be protective of,
      and relative deprivation detrimental to health, but the latter often gives a
      better account of mortality than does income alone. For some population groups
      the fit is improved in specifications which include both income and relative
      deprivation. Overall, there seems to be solid evidence in support of the relative
      income hypothesis, particularly for the more economically disadvantaged
      population groups. Relative deprivation is especially significant when age is the
      reference group, suggesting that the comparison of socio-economic standing that
      has an impact on health tends to happen within cohorts. The results are robust to
      splitting the sample into urban/rural subsamples and to looking at the incidence
      of illness as the health outcome rather than mortality. While little is known
      about the mechanisms underlying the effect of relative deprivation on health and
      mortality, the consistent evidence in favor of age as a reference group,
      particularly in a context like South Africa's suggests that intra-cohort
      comparisons should be an avenue for more in depth investigation.

PMID- 20045240
TI  - Fatty acid supplements improve respiratory, inflammatory and nutritional
      parameters in adults with cystic fibrosis.
AB  - INTRODUCTION AND AIMS: Chronic inflammation plays a major role in lung
      deterioration in cystic fibrosis (CF) patients and anti-inflammatory strategies
      have beneficial effects. To study the changes seen after a one-year course of low
      dose dietary supplements with a mixture of fatty acids in adult patients with CF
      in chronic inflammation, pulmonary status (lung function, respiratory
      exacerbations and antibiotic consumption), quality of life and anthropometric
      parameters. PATIENTS AND METHOD: Seventeen adult subjects with CF received 324 mg
      of eicosapentaenoic, 216 mg of docosahexaenoic, 480 mg of linoleic and 258 mg of
      gammalinolenic acid daily. We assessed inflammation markers, spirometry
      parameters, number and severity of respiratory exacerbations, antibiotic
      consumption, quality of life (St George's QoL), anthropometric parameters and
      serum phospholipid fatty acid composition. RESULTS: At the end of the treatment
      period TNF alpha levels fell significantly and its soluble receptors (60 and 80)
      rose significantly. Levels of IgG and IgM anti-oxidized LDL antibodies fell
      significantly. Spirometry improved significantly. Annual respiratory
      exacerbations and days of antibiotic treatment fell significantly. The
      improvement in QoL was not significant. Serum levels of docosahexaenoic, total
      omega-3 and linoleic acid rose significantly and more favourable profiles were
      seen in monoenoic acids, arachidonic acid and the arachidonic/docosahexaenoic
      ratio. The fat-free mass and hand grip dynamometry improved significantly.
      CONCLUSIONS: Low-dose supplements of n-3 and gammalinolenic fatty acids over a
      long period (one year) appears to improve pulmonary status (lung function,
      respiratory exacerbations and antibiotic consumption), inflammatory and
      anthropometric parameters in adults with CF.

PMID- 20045241
TI  - The state of systemic circulation, collapsed or preserved defines the need for
      hyperoxic or normoxic resuscitation in neonatal mice with hypoxia-ischemia.
AB  - BACKGROUND: The return of spontaneous circulation (ROSC) is a primary goal of
      resuscitation. For neonatal resuscitation the International Liaison Committee on
      Resuscitation (ILCOR) recommends oxygen concentrations ranging from 21% to 100%.
      AIMS AND METHODS: This study (a) compared the efficacy of resuscitation with room
      air (RA) or 100% O(2) in achieving ROSC in 46 neonatal mice with circulatory
      collapse induced by lethal hypoxia-ischemia (HI) and (b) determined whether re
      oxygenation with RA or 100% O(2) alters the extent of HI cerebral injury in mice
      with preserved systemic circulation (n=31). We also compared changes in
      generation of reactive oxygen species (ROS) in cerebral mitochondria in response
      to re-oxygenation with RA or 100% O(2). RESULT: In HI-mice with collapsed
      circulation re-oxygenation with 100% O(2) versus RA resulted in significantly
      greater rate of ROSC. In HI-mice with preserved systemic circulation and regional
      (unilateral) cerebral ischemia the restoration of cerebral blood flow was
      significantly faster upon re-oxygenation with 100% O(2), than RA. However, no
      difference in the extent of brain injury was detected. Regardless of the mode of
      re-oxygenation, reperfusion in these mice was associated with markedly
      accelerated ROS production in brain mitochondria. CONCLUSION: In murine HI
      associated with circulatory collapse the resuscitation limited to re-oxygenation
      with 100% O(2) is superior to the use of RA in achievement of the ROSC. However,
      in HI-mice with preserved systemic circulation hyperoxic re-oxygenation has no
      benefit over the normoxic brain recovery.

PMID- 20045242
TI  - Factors influencing success of pelvic organ prolapse repair using porcine dermal
      implant Pelvicol.
AB  - OBJECTIVE: To evaluate factors influencing pelvic organ prolapse (POP) recurrence
      after repair surgery with a porcine dermal collagen implant (Pelvicol). STUDY
      DESIGN: From December 2003 to August 2005, 78 patients with mainly stage 3 pelvic
      organ prolapse by the Pelvic Organ Prolapse Quantification (POP-Q) system
      underwent vaginal repair using porcine dermal implant. Assessments were made
      preoperatively and at 6 weeks and one year follow-up. These included physical
      examination with POP-Q, Incontinence Impact Questionnaire, Urogenital Distress
      Inventory and the Defaecatory Distress Inventory and questions from the Patient
      Global Impression of Improvement. Data were recorded on changes in functional
      status, mesh erosion and adverse events. Procedural success was defined as POP-Q
      stage 0/1. RESULTS: 71 patients returned for one year follow-up. The overall cure
      rate was 74.6%. The chance of a successful operation in the younger group was
      significantly higher than in the older group (OR: 7.5; 95% CI 1.38, 40.69), but
      this effect is lower and no longer significant after adjusting for compartment
      (post, anterior, post+anterior) (adjusted OR: 5.5; 95% CI 0.92, 32.6).
      CONCLUSIONS: A low complication rate and satisfactory overall results were
      observed in a group of women after POP repair surgery with Pelvicol. Whether
      these results are better or worse than with conventional surgery or non
      resorbable mesh implantation is unclear and can only be determined in a
      randomized controlled trial. There was a strong tendency towards better results
      in the younger women than in the older women, but the reason for this phenomenon
      is unclear.

PMID- 20045243
TI  - Homology modeling, docking, and molecular dynamics reveal HR1039 as a potent
      inhibitor of 2009 A(H1N1) influenza neuraminidase.
AB  - The neuraminidase of the influenza virus is the target of antiviral drugs
      oseltamivir and zanamivir. Clinical practices have shown that zanamivir and
      oseltamivir are effective in treating the 2009 A(H1N1) influenza virus. However,
      drug resistance strains are also emerging. Herein, we report the findings from
      homology modeling and molecular simulations of 2009 A(H1N1) neuraminidase
      complexed with zanamivir, oseltamivir, and several herb extracts with potential
      activities. Our docked oseltamivir and zanamivir results are consistent with
      previous studies. Based on the same procedure, the docked results of herb
      extracts HR1039 and HR1040 suggest that they are potential potent inhibitors of
      neuraminidase. Also, the binding modes of HR1039/HR1040 are different from those
      of oseltmivir and zanamivir, and may be effective in treating oseltamivir
      resistant influenza virus strains.

PMID- 20045244
TI  - New SnO2/MgAl-layered double hydroxide composites as photocatalysts for cationic
      dyes bleaching.
AB  - A new type of nanocomposite containing SnO(2) has been obtained by wet
      impregnation of dehydrated Mg/Al-hydrotalcite-type compounds with ethanolic
      solutions of SnCl(4).2H(2)O. Tin chloride hydrolysis was achieved using NaOH or
      NH(4)OH aqueous solutions, at pH around 9, followed by the conversion into
      corresponding hydroxides through calcinations. The powder X-ray diffraction
      (PXRD) and UV-Vis diffuse reflectance (UV-DR) methods confirmed the structure of
      as-synthesized solids. The chemical composition and morphology of the synthesized
      materials were investigated by energy dispersive X-ray analysis (EDX), scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM). The as
      synthesized materials were used for photocatalytic studies showing a good
      activity for methylene blue decolourization, which varies with SnO(2) content and
      used as a hydrolysing agent. The proposed mechanism is based on the shifting of
      flat band potential of SnO(2) due to the interaction with Mg/Al-LDH, this being
      energetically favourable to the formation of hydroxyl radicals responsible for
      methylene blue degradation.

PMID- 20045245
TI  - Catalytic wet oxidation of thiocyanate with homogeneous copper(II) sulphate
      catalyst.
AB  - The wet oxidation of thiocyanate has been investigated in a semi-batch reactor at
      temperatures between 423 and 473 K and pressures between 6.1 x 10(3) and 1.0 x
      10(4)kPa in the presence of copper(II) sulphate as catalyst. The effects of
      copper concentration, initial thiocyanate concentration, pressure and temperature
      on the reaction rate were analyzed and the main products of reaction were
      identified. A kinetic model for the Cu-catalyzed reaction is here proposed,
      including temperature, oxygen concentration, and the reduction of Cu(2+) to Cu(+)
      that gives an accurate prediction of the oxidation process under the assayed
      conditions. A mechanistic model based on the formation of a transition complex
      between a copper cation and two thiocyanate anions has been proposed for the
      catalytic wet oxidation.

PMID- 20045246
TI  - Recovery of high-purity silver directly from dilute effluents by an emulsion
      liquid membrane-crystallization process.
AB  - An emulsion liquid membrane (ELM)-crystallization process, using hypophosphorous
      acid as a reducing agent in the internal aqueous phase, has been developed for
      the purpose of recovering high-purity silver directly from dilute industrial
      effluents (waste rinse water). After pretreatment with HNO(3), silver in waste
      rinse water can be reliably recovered with high efficiency through the
      established process. The main parameters in the process of ELM-crystallization
      include the concentration of carrier in the membrane phase, the concentration of
      reducing agent in the internal aqueous phase, and the treatment ratio, which
      influence the recovery efficiency to various extents and must be controlled
      carefully. The results indicated that more than 99.5% (wt.) of the silver ions in
      the external aqueous phase were extracted by the ELM-crystallization process,
      with an average efficiency of recovery of 99.24% (wt.) and a purity of 99.92%
      (wt.). The membrane phase can be used repeatedly without loss of the efficiency
      of recovery.

PMID- 20045247
TI  - Shock and detonation properties of solid explosives with gaseous products.
AB  - We present a simple theoretical model to calculate shock and detonation
      properties of solid explosives. A solid equation of state of the Mie-Gruneisen
      form based on interatomic potential of the Lennard-Jones type with a soft
      repulsive part is used to calculate the shock properties of solid explosives. In
      conjunction with the Chapman-Jouguet condition, a reliable dense fluid equation
      of state and a simple mixing rule are used to calculate detonation properties of
      solid explosives with gaseous products. Calculations show a satisfactory
      agreement with experimental data and with results obtained from other theoretical
      modes.

PMID- 20045248
TI  - QSAR modeling of toxicity of diverse organic chemicals to Daphnia magna using 2D
      and 3D descriptors.
AB  - One of the major economic alternatives to experimental toxicity testing is the
      use of quantitative structure-activity relationships (QSARs) which are used in
      formulating regulatory decisions of environmental protection agencies. In this
      background, we have modeled a large diverse group of 297 chemicals for their
      toxicity to Daphnia magna using mechanistically interpretable descriptors. Three
      dimensional (3D) (electronic and spatial) and two-dimensional (2D) (topological
      and information content indices) descriptors along with physicochemical parameter
      logK(o/w) (n-octanol/water partition coefficient) and structural descriptors were
      used as predictor variables. The QSAR models were developed by stepwise multiple
      linear regression (MLR), partial least squares (PLS), genetic function
      approximation (GFA), and genetic PLS (G/PLS). All the models were validated
      internally and externally. Among several models developed using different
      chemometric tools, the best model based on both internal and external validation
      characteristics was a PLS equation with 7 descriptors and three latent variables
      explaining 67.8% leave-one-out predicted variance and 74.1% external predicted
      variance. The PLS model suggests that higher lipophilicity and electrophilicity,
      less negative charge surface area and presence of ether linkage, hydrogen bond
      donor groups and acetylenic carbons are responsible for greater toxicity of
      chemicals. The developed model may be used for prediction of toxicity, safety and
      risk assessment of chemicals to achieve better ecotoxicological management and
      prevent adverse health consequences.

PMID- 20045249
TI  - Removal of high concentration dimethyl methylphosphonate in the gas phase by
      repeated-batch reactions using TiO2.
AB  - The aim of our study is to develop apparatuses that use TiO(2) for effective
      decontamination of air contaminated by Sarin gas. We performed photocatalytic
      decomposition of gaseous dimethyl methylphosphonate (DMMP) by TiO(2) and
      identified the oxidization products. The high activity of TiO(2) (0.01 g) was
      observed under UV-light irradiation and high concentration DMMP (33.5 microM) was
      removed rapidly. On the other hand, DMMP was not decreased under UV-light
      irradiation without TiO(2). This indicates that photocatalytic treatment is very
      effective for the removal of DMMP. Methanol, formaldehyde, formic acid, methyl
      formate, CO, CO(2) and H(2)O were detected as the primary products. In the gas
      phase, no highly poisonous substances were detected. In order to examine the
      performance of photocatalytic activity during long-term reactions, we performed
      photocatalytic decomposition by repeated-batch reactions using TiO(2). High
      photocatalytic activities decreased gradually. Meanwhile, the strong adsorption
      of TiO(2) against DMMP was observed as photocatalytic activities decreased.
      During the repeated-batch reactions with the sample scaled up (TiO(2): 0.1g), the
      total amount of removed DMMP reached 968.5 microM by both photocatalytic
      decomposition and the strong adsorption of TiO(2). These results suggest the
      possibility of removing large amounts of DMMP.

PMID- 20045250
TI  - Uptake of Pb by hydrozincite, Zn5(CO3)2(OH)6--implications for remediation.
AB  - Hydrozincite, Zn(5)(CO(3))(2)(OH)(6), periodically precipitates from heavy metal
      contaminated waters of the Rio Naracauli stream, Sardinia, in association with a
      biological photosynthetic community. The precipitation removes not only zinc from
      the waters, but also other toxic "heavy metals", such as Cd, Cu, Pb. The
      phenomenon is therefore of potential interest for "soft" remediation of
      contaminated waters. Previous cation exchange experiments suggested that binding
      of Pb to hydrozincite is fairly strong. This suggestion is in agreement with new
      release tests in deionized water and X-ray absorption spectroscopy (XAS) spectra
      collected at the Pb L(III) edge for natural hydrozincites from Naracauli, and
      synthetic Pb-doped hydrozincites. The results suggest that, up to bulk
      concentration of 1.5 wt.% Pb, uptake of this metal occurs in two distinct ways:
      (1) as a substitution for Zn in the tetrahedral site of the hydrozincite
      structure, possibly via formation of a surface mononuclear tridentate inner
      sphere complex; (2) as an ill-defined, presumably amorphous, phase with a local
      atomic structure similar to cerussite. These data support the concept that Pb
      binding to hydrozincite is strong enough to make this mineral a potential sink
      for the metal.

PMID- 20045251
TI  - A novel adsorbent obtained by inserting carbon nanotubes into cavities of
      diatomite and applications for organic dye elimination from contaminated water.
AB  - A novel approach is described for establishing adsorbents for elimination of
      water-soluble organic dyes by using multi-walled carbon nanotubes (MWCNTs) as the
      adsorptive sites. Agglomerates of MWCNTs were dispersed into individual tubes
      (dispersed-MWCNTs) using sodium n-dodecyl itaconate mixed with 3-(N,N
      dimethylmyristylammonio)-propanesulfonate as the dispersants. The resultant
      dispersed-MWCNTs were inserted into cavities of diatomite to form composites of
      diatomite/MWCNTs. These composites were finally immobilized onto the cell walls
      of flexible polyurethane foams (PUF) through an in situ PUF formation process to
      produce the foam-like CNT-based adsorbent. Ethidium bromide, acridine orange,
      methylene blue, eosin B, and eosin Y were chosen to represent typical water
      soluble organic dyes for studying the adsorptive capabilities of the foam-like
      CNT-based adsorbent. For comparisons, adsorptive experiments were also carried
      out by using agglomerates of the sole MWCNTs as adsorbents. The foam-like CNT
      based adsorbents were found to have higher adsorptive capacities than the CNT
      agglomerates for all five dyes; in addition, they are macro-sized, durable,
      flexible, hydrophilic and easy to use. Adsorption isotherms plotted based on the
      Langmuir equation gave linear results, suggesting that the foam-like CNT-based
      adsorbent functioned in the Langmuir adsorption manner. The foam-like CNT-based
      adsorbents are reusable after regeneration with aqueous ethanol solution.

PMID- 20045253
TI  - Rapid detection of Dirofilaria immitis in mosquito vectors and dogs using a real
      time fluorescence resonance energy transfer PCR and melting curve analysis.
AB  - A real-time fluorescence resonance energy transfer (FRET) PCR supplemented with
      melting curve analysis for the rapid molecular detection of Dirofilaria immitis
      in mosquito vectors and dog blood samples was developed. This real-time FRET PCR
      was based on the fluorescence melting curve analysis of a hybrid between an
      amplicon generated from the D. immitis ribosomal RNA gene sequence and specific
      fluorophore-labeled probes. The sensitivity, specificity, accuracy, and positive
      and negative predictive values of this method were all 100%. Besides being highly
      sensitive and specific, this PCR is fast and offers a high throughput. Therefore
      it is a suitable and powerful tool for the diagnosis and for epidemiological
      surveys of canine dirofilariasis as well as for molecular xenomonitoring of D.
      immitis in mosquito vectors.

PMID- 20045252
TI  - Differential purinergic signaling in bladder sensory neurons of naive and bladder
      inflamed mice.
AB  - This study explored purinergic signaling in lumbosacral (LS) and thoracolumbar
      (TL) dorsal root ganglion neurons innervating the urinary bladder. In naive mice,
      a greater proportion of LS (93%) than that of TL (77%) bladder neurons responded
      to purinergic agonists. Three types of purinergic currents were identified:
      'sustained' (homomeric P2X2) currents were detected only in LS neurons, rapidly
      activating, 'slow' deactivating (heteromeric P2X2/3) currents predominated in
      both LS and TL neurons, and 'fast' activating/de-activating (homomeric P2X3)
      currents were detected only in TL neurons. Relative to TL bladder neurons, slow
      current density was greater in LS neurons, which also had a more negative action
      potential threshold and generated more action potentials in response to
      purinergic agonists (suggesting greater excitability of LS neurons). Single cell
      nested PCR documented P2X2 and P2X3 subunit expression in both TL and LS bladder
      neurons. Relative to saline treatment, bladder wall thickness and weight
      increased after cyclophosphamide (CYP) treatment. Both LS and TL neuron
      excitability increased (rheobase was decreased and responses to purinergic
      agonists increased) after CYP treatment. The proportion of sustained currents in
      LS bladder neurons increased fourfold after CYP bladder inflammation. Although
      proportions of slow and fast purinergic currents in TL neurons were unchanged by
      CYP treatment, the fast current density was greater than in saline-treated mice.
      These results in mouse, as previously described in rat, reveal differential
      purinergic signaling in TL and LS bladder neurons. The predominant currents and
      significant changes after inflammation, however, occur in different
      ganglia/sensory pathways in mouse and rat.

PMID- 20045254
TI  - Use of a reverse line blot assay to survey small strongyle (Strongylida:
      Cyathostominae) populations in horses before and after treatment with ivermectin.
AB  - A sensitive and specific PCR hybridization assay was applied for species-specific
      monitoring of the small strongyle (Strongylida: Cyathostominae) populations in
      horses in a herd before and after treatment with the anthelmintic drug
      ivermectin. Fecal samples were collected pre- and post-treatment weekly from
      eight individual horses (four foals and four yearlings) for 6 weeks to determine
      counts of strongyle eggs per gram of feces (EPGs). Additionally, one foal and one
      yearling were nontreated controls. Also, one horse, from another herd known to be
      infected with Strongylus spp., was a positive control for these parasites.
      Genomic DNA was obtained from eggs in groups of approximately 6000-7000 eggs
      except for two samples containing low EPGs in which 450 eggs were used.
      Amplification of the intergenic spacers (IGSs) of ribosomal DNA (rDNA) of small
      and large strongyles followed by reverse line blot (RLB) assay were performed to
      identify the presence of the 12 most common equine small strongyle species and to
      discriminate them from Strongylus spp. Overall, 11 small strongyle species were
      identified in pretreatment samples. In the samples collected at 4 weeks after
      ivermectin treatment, eight small strongyle species were identified and four of
      them were predominant (Cylicocyclus nassatus, Cylicostephanus longibursatus,
      Cylicostephanus calicatus and Cylicostephanus minutus). At 5 and 6 weeks post
      treatment, the RLB assay analysis showed almost the same composition in the small
      strongyle population as before treatment. Strongylus spp. were identified only in
      samples collected from the positive control horse for these parasites. These data
      confirm the ability of the PCR-RLB technique for simultaneous species-specific
      differentiation of equine strongyle eggs, indicating a valuable way of furthering
      drug-resistance studies.

PMID- 20045255
TI  - Toxoplasmosis and genotyping of Toxoplasma gondii in Macropus rufus and Macropus
      giganteus in Argentina.
AB  - Toxoplasma gondii infection is frequently asymptomatic; however, it can be severe
      or even fatal to some hosts. In this study, diagnosis of disseminated
      toxoplasmosis in one red kangaroo (Macropus rufus) and one great grey kangaroo
      (Macropus giganteus) from the La Plata Zoo, Argentina and the isolation and
      molecular characterization of T. gondii are reported. Both male kangaroos showed
      depression and sudden death. Toxoplasma gondii infection was diagnosed by fresh
      examination, histopathology, immunohistochemistry, PCR and bioassay in mice.
      During fresh examination many protozoan cysts were observed in diaphragm, heart
      and hind limb muscles of M. rufus. Cysts were also observed in samples from M.
      giganteus, although in lower number. Cysts from both kangaroos stained strongly
      with T. gondii anti-serum by immunohistochemistry. The M. rufus showed more
      considerable histopathological lesions like non-suppurative meningoencephalitis,
      myositis and myocarditis. All mice inoculated with tissues from both kangaroos
      developed IFAT titers to T. gondii (titer >or=800) and brain cysts at necropsy.
      Both T. gondii isolates were maintained by mice passages and the M. rufus isolate
      was also maintained in cell culture. Toxoplasma gondii DNA from tissue samples
      was analyzed by PCR-RFLP analysis using the markers 5'SAG2, 3'SAG2, BTUB, GRA6,
      SAG3, c22-8, L358, PK1, c29-2 and Apico. Genotyping revealed that the T. gondii
      isolate from M. rufus was clonal type III and the isolate from M. giganteus was
      clonal type II. This is the first report of disseminated toxoplasmosis in M.
      rufus and M. giganteus in Argentina caused by genotypes of T. gondii considered
      non-virulent in a mouse model.

PMID- 20045256
TI  - Effects of orally administered spinosad (Comfortis) in dogs on adult and immature
      stages of the cat flea (Ctenocephalides felis).
AB  - The efficacy of spinosad against adult fleas (Ctenocephalides felis) on dogs was
      evaluated in three controlled, blinded studies. One study was conducted to
      determine speed of kill on experimentally infested dogs. Two additional studies
      were designed to assess the efficacy of spinosad in preventing environmental
      contamination with flea eggs (USA study and EU study). An additional objective of
      the USA study was to assess the effects of skin and hair-coat debris from
      spinosad-treated dogs on eggs and larvae of C. felis. Dogs were randomly
      allocated to treatment with beef-flavored spinosad tablets, administered orally
      at a minimum dosage of 30mg/kg, or placebo. In the first study, speed of kill was
      determined by flea comb counts performed at 0.5, 1, 2, 4, 8, 12, 24 and 48h after
      spinosad treatment. Reductions in geometric mean flea counts for spinosad-treated
      dogs, compared to placebo were 53.7% at 0.5h, 64.2% at 1h, 85.8% at 2h and 100%
      at 4 through 48h post-treatment (p<0.05 at 1h and beyond). In the 2 flea egg
      production studies, dogs were treated (spinosad or placebo) once on day 0,
      infested with 600 fleas approximately 3h post-treatment and reinfested with
      approximately 600 fleas at intervals over 1 month. Flea eggs were collected
      starting at approximately 72h after each infestation. Eggs were examined for any
      effects of spinosad on egg viability. Efficacy of spinosad was also evaluated
      against environmental eggs and larvae exposed to canine hair-coat debris
      collected on days 3, 7, 14, 21, and 30. Spinosad was highly effective in reducing
      flea egg production (>99.8% across the entire study period) compared to control
      dogs in both egg collection studies. Insufficient numbers of eggs were recovered
      from spinosad-treated dogs to determine the viability of those eggs. There was no
      evidence of any effect on environmental flea stages, indicating that spinosad was
      not present in the skin debris of spinosad-treated dogs. The capability of
      spinosad to quickly kill adult fleas, and to greatly reduce egg production
      following challenge with high numbers of adult fleas is important in breaking the
      flea life cycle and preventing the introduction and establishment of new flea
      infestations in the household.

PMID- 20045257
TI  - Psoroptic mange infestation increases oxidative stress and decreases antioxidant
      status in sheep.
AB  - The present study was aimed to examine the status of nutritional and enzymatic
      antioxidants and oxidative stress indices in blood, skin and brain tissues of
      sheep with Psoroptic mange. Seventy-five sheep were divided into three equal
      groups, healthy control (group I, n=25), sub-clinical Psoroptic mange (group II,
      n=25) and clinical Psoroptic mange (group III, n=25). Lipid peroxides (LPO),
      zinc, copper, alpha-tocopherol, ascorbic acid and ceruloplasmin concentrations in
      blood; status of LPO, superoxide dismutase (SOD), catalase (CAT), glutathione-s
      transferase (GST) in skin and LPO, SOD, CAT, copper and zinc in brain of sheep
      were measured. Ascorbic acid, zinc, copper alpha-tocopherol and ceruloplasmin
      concentrations in blood were significantly decreased in Psoroptic mange in
      comparison to control. In the skin, CAT, SOD and GST were significantly lowered,
      whereas LPO was increased in sheep with Psoroptic mange. In the brain, LPO was
      increased significantly and CAT, SOD activities and copper and zinc
      concentrations were significantly lower. From the present study, it may be
      concluded that Psoroptic mange infestation increases oxidative stress and
      decreases antioxidant status in sheep.

PMID- 20045258
TI  - Two case reports: electrothermal (aka contact) burns and the effects of current
      density, application time and skin resistance.

PMID- 20045259
TI  - Incidence and bacteriology of burn infections at a military burn center.
AB  - Considerable advancements in shock resuscitation and wound management have
      extended the survival of burned patients, increasing the risk of serious
      infection. We performed a 6-year review of bacteria identification and antibiotic
      susceptibility records at the US Army Institute of Surgical Research Burn Center
      between January 2003 and December 2008. The primary goal was to identify the
      bacteria recovered from patients with severe burns and determine how the
      bacteriology changes during extended hospitalization as influenced by population
      and burn severity. A total of 460 patients were admitted to the burn ICU with
      3507 bacteria recovered from 13,727 bacteriology cultures performed. The most
      prevalent organisms recovered were Acinetobacter baumannii (780), Pseudomonas
      aeruginosa (703), Klebsiella pneumoniae (695) and Staphylococcus aureus (469). A.
      baumannii was most often recovered from combat-injured (58%) and S. aureus the
      most frequent isolate from local (46%) burn patients. Culture recovery rate of A.
      baumannii and S. aureus was highest during the first 15 hospital days (73% and
      71%); while a majority of P. aeruginosa and K. pneumoniae were recovered after
      day 15 (63% and 53%). All 4 pathogens were recovered throughout the course of
      hospitalization. A. baumannii was the most prevalent pathogen recovered from
      patients with total body surface area (TBSA) burns less than 30% (203) and 30-60%
      (338) while P. aeruginosa was most prevalent in patients with burns greater than
      60% TBSA (292). Shifting epidemiology of bacteria recovered during extended
      hospitalization, bacteriology differences between combat-injured and local burn
      patients, and impact of % TBSA may affect patient management decisions during the
      course of therapy.

PMID- 20045260
TI  - Imipenem-resistant Pseudomonas aeruginosa strains carry metallo-beta-lactamase
      gene bla(VIM) in a level I Iranian burn hospital.
AB  - INTRODUCTION: In this study, we aimed to determine the distribution of bla(VIM)
      and bla(IMP) transferable genes in Pseudomonas aeruginosa isolates from infected
      burn wounds in an Iranian level I burn care center. These genes confer imipenem
      resistance and increase the mortality rate of burn patients. METHODS: P.
      aeruginosa isolates from burn patients were tested for antibiotic susceptibility
      with Kirby-Bauer disk diffusion method and for production of metallo-beta
      lactamase (MBL) by EDTA disk method. DNA was purified from isolates with positive
      MBL results and underwent PCR for detection of bla(VIM) and bla(IMP) genes.
      RESULTS: MBL was produced by 23 imipenem-resistant isolates and bla(VIM) gene was
      detected in all of these isolates. None of the isolates carried bla(IMP) gene.
      Mortality rate of infection with MBL-producing Pseudomonas strains was 82.6% in
      this hospital while the mortality rate for non-MBL-producing Pseudomonas was
      22.7%. CONCLUSION: We found that all MBL-producing isolates in this hospital
      carry bla(VIM) gene. This result is similar to the previous Iranian study and
      emphasizes the importance of VIM family of MBLs in Iran. Timely identification of
      these strains and strict isolation methods can prevent spread of this
      transferable gene to other Gram-negative bacteria and prevent the subsequent
      outbreak of high mortality.

PMID- 20045261
TI  - Time course of pro- and anti-inflammatory cytokine levels in patients with burns-
      prognostic value of interleukin-10.
AB  - INTRODUCTION: Trends and the prognostic value of cytokine responses to severe
      burns have not been fully examined in humans. Therefore, the aim of this study
      was to determine the time course and prognostic value of pro- and anti
      inflammatory cytokines in the immediate post-burn period. PATIENTS AND METHODS:
      Blood samples were taken for measuring IL-1 beta, IL-6, IL-8, IL-10, IL-12p70 and
      TNF-alpha concentrations from patients with more than 20% burned surface area on
      admission and on 5 consecutive days. Development of sepsis was assessed using
      standard criteria twice a day. RESULTS: IL-12p70 remained under assay detection
      levels in the study period. IL-1 beta and TNF-alpha could be detected in
      stimulated blood samples with higher levels in survivors (n=21). IL-6 on days 4-5
      and IL-8 on days 4-6 in non-stimulated plasma showed significant elevation in non
      survivors (n=18) whereas in stimulated blood its levels did not differ
      significantly. IL-10 levels were significantly higher in non-survivors during the
      study period in non-stimulated, and except day 6 in stimulated blood. Using the
      cut-off level of 14 pg ml(-1) for IL-10 predicted ICU mortality with 85.4%
      sensitivity and 84.2% specificity on admission. CONCLUSION: Early anti
      inflammatory excess had a bad prognosis for patients suffering from severe burns.

PMID- 20045262
TI  - Whose opinion matters? The relationship between injunctive norms and alcohol
      consequences in college students.
AB  - Harm reduction approaches may benefit from research extending the exploration of
      predictors of alcohol use per se to those components most directly related to
      alcohol-related harm. This investigation evaluated the relationship between
      perceived injunctive norms of alcohol use (level of approval of drinking
      behaviors in specific situations) and the experience of alcohol-related
      consequences as a function of typical student reference groups at increasing
      levels of similarity to the respondent: based on race, gender, Greek status, and
      combinations of these dimensions, as well as parents, close friends, and the
      students' own attitudes. Participants were 3753 students (61% female) from two
      campuses who completed an online survey. Preliminary analyses determined that
      there were no differences in the relationship between perceived injunctive norms
      and consequences across the eight student groups of varying specificity, thus all
      eight levels were combined into one variable of perceived student injunctive
      norms. However, the relationship between this variable and consequences was
      weaker than the perceived attitudes of more proximal referents (parents, close
      friends, as well as their own personal attitudes). Subsequent analyses predicting
      consequences while controlling for demographic variables and drinking level,
      revealed that perceived injunctive norms for students, parents, and close friends
      as well as personal attitudes each significantly predicted consequences. Results
      suggest an important role for perceived injunctive norms in the experiencing of
      consequences over and above the amount of consumption and point to types of
      injunctive norms feedback that might form effective interventions (i.e.,
      incorporating close friend and parent feedback as well as general student
      feedback).

PMID- 20045263
TI  - Intrathecal injection of urokinase: a promising therapeutic method for acute
      hydrocephalus?

PMID- 20045264
TI  - Earphone: a new approach to enhance mandibular growth in class II malocclusion.

PMID- 20045265
TI  - Pretty painful: why does tooth bleaching hurt?
AB  - Vital bleaching procedures are a popular means of improving the appearance of
      discolored teeth. There is a wide array of whitening products for home and dental
      office use; all involves placing peroxide containing gels or solutions in contact
      with the teeth. In order to whiten teeth peroxide has to be able to penetrate
      tooth structure and oxidize colored compounds in the dentin. Unfortunately beauty
      comes with a price; many patients undergoing peroxide based whitening procedures
      complain of bleaching sensitivity (BS) arising in the treated teeth. In BS, pain
      can occur in healthy intact teeth without any provoking stimulus. Currently the
      mechanism of nociceptors activation in BS is unknown. A more common form of
      dental pain-dentin sensitivity (DS) occurs when stimuli such as cold or tactile
      stimulation contact areas of exposed dentin in otherwise healthy teeth. In DS,
      stimulation of the dentin results in fluid shifts in the dentinal tubules, these
      fluid shifts activate mechanosensitive nerve endings in the deep dentin and pulp.
      Since many aspects of BS and DS symptoms differ, it is hypothesized that that the
      mechanism of pain generation differs for these two conditions. Recently the
      functional properties of a chemosensitive ion channel-TRPA1 have been described.
      This channel is activated by a variety of oxidizer compounds including hydrogen
      peroxide. Pulpal sensory afferents express TRPA1. It is hypothesized that direct
      activation of intradental nerve activity via TRPA1 is the mechanism of BS pain.
      If this theory were correct, tooth sensitivity treatments that reduce the
      excitability of the intradental nerves such as potassium salts, would be the
      treatment of choice for BS.

PMID- 20045266
TI  - Long-term follow-up of dose-adapted and reduced-field radiotherapy with or
      without chemotherapy for central nervous system germinoma.
AB  - PURPOSE: To update our institutional experience with neoadjuvant chemotherapy and
      minimized radiotherapy vs. radiation monotherapy for intracranial germinoma.
      METHODS AND MATERIALS: We retrospectively reviewed records of 59 patients with
      diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was
      irradiation alone or neoadjuvant platinum-based chemotherapy and local
      irradiation (initial tumor plus margin) for patients with localized complete
      response and reduced-dose craniospinal irradiation for others. RESULTS: For the
      chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died.
      The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years.
      In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young
      male patients who received 30.6 Gy to local fields after complete response to
      chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more
      extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median
      follow-up was 15 years. Overall and disease-free survival rates were 93% and 93%
      at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to
      4.9 years after diagnosis. Most patients in this group were young men 18 to 23
      years of age with suprasellar primary disease treated with about 50 Gy to local
      fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive
      fields (p < .01). CONCLUSIONS: The addition of neoadjuvant chemotherapy to local
      field radiotherapy reduced central nervous system cancer recurrence when high
      risk patients were excluded by thorough pretreatment staging. There was trend
      toward improved central nervous system tumor control when larger fields (whole
      brain, whole ventricle, or craniospinal axis) were used.

PMID- 20045267
TI  - External beam radiation therapy after transurethral resection of the prostate: a
      report on acute and late genitourinary toxicity.
AB  - PURPOSE: To describe genitourinary (GU) toxicity in men with a history of
      transurethral resection of the prostate (TURP) treated with external beam
      radiation therapy (EBRT) for prostate cancer. METHODS AND MATERIALS: Seventy-one
      men with a history of TURP were treated with EBRT for prostate cancer. The median
      time from TURP to EBRT was 15 months. The median EBRT dose was 70 Gy, and 21 men
      (30%) received androgen deprivation therapy (ADT). Acute GU toxicity and late GU
      toxicity were scored by Radiation Therapy Oncology Group criteria and compared
      with a cohort of 538 men without prior TURP. The median follow-up for men with
      TURP and men without TURP was 40 months and 50 months, respectively (p = 0.7605).
      RESULTS: The rate of acute Grade 2 GU toxicity or higher was 41%, and was
      increased with a history of more than 1 TURP (73% vs. 31%, p = 0.0036). The 4
      year rate of freedom from late Grade 3 GU toxicity or higher was 84%, and was
      decreased with ADT (45% vs. 95% without ADT, p = 0.0024). By last follow-up,
      maximal GU toxicity tended to resolve (p < 0.0001) and there was no worsening of
      urinary symptom scores (p = 0.6911). Compared to men without a prior TURP, TURP
      patients had a lower rate of freedom from late Grade 3 toxicity or higher (84%
      vs. 96%, p = 0.0483). Multivariate analysis suggested a higher rate of late Grade
      3 toxicity or higher with TURP (risk ratio, 2.87; p = 0.0612) and EBRT dose of 74
      Gy or greater (risk ratio, 2.26; p = 0.0521). CONCLUSIONS: Men treated for
      prostate cancer with EBRT after TURP have a higher risk of severe GU toxicity;
      however, the overall incidence is low, and toxicity tends not to persist.

PMID- 20045268
TI  - Prevalence of Hepatitis E virus-specific antibodies in sera of German domestic
      pigs estimated by using different assays.
AB  - Hepatitis E virus is the causative agent of an acute hepatitis in humans. In
      industrialized countries, autochthonous hepatitis E cases in the past were mainly
      of undetermined origin, whereupon nowadays some cases may be linked to zoonotic
      transmission of HEV from pigs and wild boars. In contrast to several European
      countries the HEV status of German domestic pigs and a possible risk of
      transmission are unknown so far. Here, a novel peptide-based ELISA was used to
      detect HEV-specific antibodies in 1072 sera from German domestic pigs resulting
      in an average seroprevalence of 49.8% indicating widespread HEV infections in
      these animals. A comparative testing of 321 randomly selected sera revealed a
      seroprevalence of 64.8% when using a commercially available ELISA and 43.9% for
      the novel peptide-based ELISA but concordant results were obtained in both tests
      only for 56.1% of the sera. Additional re-testing of 23 randomly selected sera
      with a modified commercially available immunoblot revealed discordant results
      also. The use of different antigens and the measurement of different
      immunoglobulin classes are considered to be responsible for the observed
      variations of the results. Though the present study revealed a high
      seroprevalence of HEV in the German domestic pig population and a potential risk
      of transmission to humans, the differing results of the tests highlight the
      necessity of a standardization of serological assays for comparative
      seroprevalence and longitudinal studies.

PMID- 20045269
TI  - MIRU-VNTR typing adds discriminatory value to groups of Mycobacterium bovis and
      Mycobacterium caprae strains defined by spoligotyping.
AB  - The value of Mycobacterial Interspersed Repetitive Units-Variable Number Tandem
      Repeats (MIRU-VNTR) as a genotyping technique for Mycobacterium bovis and
      Mycobacterium caprae, has been confirmed in different countries and
      epidemiological scenarios. However, a standardized panel of loci has not yet been
      adopted for these species, since allelic diversity of each locus differs among
      countries. To determine the most discriminatory loci, a panel of 181 M. bovis and
      M. caprae strains representing 12 spoligotypes was created. The panel included
      strains from the three predominant spoligotypes previously isolated in Portugal;
      strains from spoligotyping group SB0140, prevalent in the British Isles but also
      detected in Portugal; strains from spoligotypes common to cattle and wildlife
      species and strains from the M. caprae spoligotyping group SB0157. MIRU-VNTR
      analysis of these strains, targeting 8 selected loci, produced 87 different
      profiles (h=0.99), being VNTR3232, QUB11a, ETR-B and ETR-A the most
      discriminatory loci (h=0.96). A single M. bovis spoligotyping group could be
      differentiated - up to 44 MIRU-VNTR profiles. These results emphasize the high
      genotype diversity of Portuguese isolates compared with other countries. MIRU
      VNTR typing was superior to spoligotyping for identifying multi-genotype infected
      herds and the combination of the two genotyping methods by a hierarchical
      approach confirmed the genetic relatedness of M. bovis isolates between cattle
      and wildlife.

PMID- 20045270
TI  - Virulence characteristics of genetically related isolates of group B streptococci
      from bovines and humans.
AB  - The present study had the objective of evaluating the pathogenic potential of the
      genetically related strains of Streptococcus agalactiae no. 80427 (human origin)
      and no. 87159 (bovine origin), and comparing the results with two other strains
      isolated from bovine mastitis (no. 87244) and invasive human infection (no.
      90356), with no genetic or epidemiologic relationship between them or with the
      first 2 isolates. Virulence genes hylB (hyaluronidase) and lmb (laminin-binding
      protein) were detected in the 4 strains, and genes bac (beta protein) and bca
      (alpha protein) were only detected in human strains. The protein profile obtained
      using SDS-PAGE did not indicate any differences between the 4 strains. No
      significant difference was detected between human and bovine strains in the
      assays of adherence to and invasion of 16HBe cells, as well as in the resistance
      assay for intracellular bacterial survival in macrophages. However, the strain
      87159 exhibited a greater survival in the killing test with whole human blood and
      was more virulent in newborn mice than the 80427 strain. The strain 87244 was not
      virulent in mice. These data suggest that isolates of human and bovine origins
      may express similar virulence attributes, leading to a possible, however limited,
      dissemination.

PMID- 20045271
TI  - Emergence of bluetongue virus serotype 6 in Europe--German field data and
      experimental infection of cattle.
AB  - In late 2008, bluetongue virus (BTV) serotype 6 (BTV-6), which had never occurred
      in Europe before, was first detected in the Netherlands and Germany. While the
      origin of the virus remains unknown, the prevalence of infections in cattle was
      investigated in a virological (N=28,658) and serological (N=2075) field survey in
      Lower Saxony, where 45 cases confined to the district Grafschaft Bentheim were
      found. Blood from affected animals was used for the experimental infection of
      three cattle with different BTV antibody status, leading to sustained viraemia in
      one animal naive for BTV. Of two animals that had detectable antibodies against
      BTV serotype 8, one became transiently infected and seroconverted for BTV-6 while
      the other did not react. In conclusion, while only a very limited spread of BTV-6
      could be observed in the field, experimental infection of cattle did not show
      substantial differences of the course of infection in comparison to other BTV
      serotypes.

PMID- 20045272
TI  - Can the prevalence of high blood drug concentrations in a population be estimated
      by analysing oral fluid? A study of tetrahydrocannabinol and amphetamine.
AB  - AIM: To study several methods for estimating the prevalence of high blood
      concentrations of tetrahydrocannabinol and amphetamine in a population of drug
      users by analysing oral fluid (saliva). METHODS: Five methods were compared,
      including simple calculation procedures dividing the drug concentrations in oral
      fluid by average or median oral fluid/blood (OF/B) drug concentration ratios or
      linear regression coefficients, and more complex Monte Carlo simulations.
      Populations of 311 cannabis users and 197 amphetamine users from the Rosita-2
      Project were studied. RESULTS: The results of a feasibility study suggested that
      the Monte Carlo simulations might give better accuracies than simple calculations
      if good data on OF/B ratios is available. If using only 20 randomly selected OF/B
      ratios, a Monte Carlo simulation gave the best accuracy but not the best
      precision. Dividing by the OF/B regression coefficient gave acceptable accuracy
      and precision, and was therefore the best method. None of the methods gave
      acceptable accuracy if the prevalence of high blood drug concentrations was less
      than 15%. CONCLUSION: Dividing the drug concentration in oral fluid by the OF/B
      regression coefficient gave an acceptable estimation of high blood drug
      concentrations in a population, and may therefore give valuable additional
      information on possible drug impairment, e.g. in roadside surveys of drugs and
      driving. If good data on the distribution of OF/B ratios are available, a Monte
      Carlo simulation may give better accuracy.

PMID- 20045274
TI  - [Anoperineal tuberculosis: 40 cases].

PMID- 20045273
TI  - [Time trends in demographic and clinical characteristics of adult patients on
      HAART initiation in West Africa].
AB  - OBJECTIVE: We studied the evolution of drug combinations used, as well as the
      clinical and immunological profile of patients at initiation of highly active
      antiretroviral therapy (HAART) between 1996 and 2006 in West Africa. SETTINGS AND
      METHOD: IeDEA West Africa is a network of HIV care programs established in 2006.
      We analyzed data from 12 clinical centers treating adults in five countries:
      Benin, Cote d'Ivoire, Senegal, Gambia, and Mali. Patients 16 years of age or over
      were included in the study and the following was documented: sex, date of birth
      and date of initiation of HAART. RESULTS: We included 14,496 adult patients
      having started HAART, among these 55 % had started HAART between 2005-2006. The
      proportion of HIV-infected women increased from 46 % in 1996-2000 to 63 % in 2005
      2006. The median age at HAART initiation remained constant: 35 years for women
      and 40 years for men. The proportion of patients having started HAART with a CD4
      count<200 cells/microl was 54 % in 1996-2000, and 64 % in 2005-2006. The most
      frequently prescribed HAART was: AZT/3TC (or d4T/DDI)/IDV (27 %) in 1996-2000;
      d4T (or AZT)/3TC/EFV (49 %) in 2003-2004, and d4T/3TC/NVP (49 %) in 2005-2006.
      CONCLUSION: The first line HAART regimen recommended by WHO was initiated in 83 %
      of cases in 2005-2006. New approaches to an earlier initiation of ART should be
      explored to reduce mortality in HIV-infected patients on HAART.

PMID- 20045275
TI  - Development and validation of a stability indicating RP-HPLC method for the
      simultaneous determination of related substances of albuterol sulfate and
      ipratropium bromide in nasal solution.
AB  - A simple, sensitive and specific RP-HPLC method was developed for the
      quantification of related impurities of albuterol sulfate (AS) and ipratropium
      bromide (IB) in liquid pharmaceutical dosage form. The chromatographic separation
      employs gradient elution using an inertsil C8-3, 250mmx4.6mm, 5mum columns.
      Mobile phase consisting of solvent A (solution containing 2.5g of potassium
      dihydrogen phosphate and 2.87g of heptane-1-sulfonic acid sodium salt per liter
      of water, adjusted to pH 4 with orthophosphoric acid) and solvent B
      (acetonitrile) delivered at a flow rate of 1.0mlmin(-1). The analytes were
      detected and quantified at 210nm using photodiode array (PDA) detector. The
      method was validated as per ICH guidelines, demonstrating to be accurate and
      precise (repeatability and intermediate precision level) within the corresponding
      linear range of known impurities of AS and IB. The specificity of the method was
      investigated under different stress conditions including hydrolytic, oxidative,
      photolytic and thermal as recommended by ICH guidelines. Relevant degradation was
      found to take place under hydrolytic and oxidative conditions. Robustness against
      small modification in pH, column oven temperature, flow rate and percentage of
      the mobile phase composition was ascertained. Lower limit of quantification and
      detection were also determined. The peak purity indices (purity angle<purity
      threshold) obtained with the aid of PDA detection and satisfactory resolution
      between related impurities established the specificity of the determination. All
      these results provide the stability indicating capability of the method.

PMID- 20045276
TI  - Ultra high-pressure liquid chromatographic assay of moxifloxacin in rabbit
      aqueous humor after topical instillation of moxifloxacin nanoparticles.
AB  - The present report describes a rapid and sensitive ultra high-pressure liquid
      chromatography (UHPLC) method with UV detection to quantify moxifloxacin in
      rabbit aqueous humor. After deproteinisation with acetonitrile, gradient
      separation of moxifloxacin was achieved on a Waters Acquity BEH C18 (50mmx2.1mm,
      1.7microm) column at 50 degrees C. The mobile phase consisted of 0.1%
      trifluoroacetic acid in water and acetonitrile at a flow rate of 0.4ml/min.
      Detection of moxifloxacin was done at 296nm. Method was found to be selective,
      linear (r=0.9997), accurate (recovery, 97.30-99.99%) and precise (RSD, <or=1.72%)
      in the selected concentration range of 10-1000ng/ml. Detection and quantitation
      limit of moxifloxacin in aqueous humor were 0.75 and 2.5ng/ml, respectively. The
      aqueous humor levels of moxifloxacin after single topical instillation in three
      formulations, i.e. moxifloxacin solution (Moxi-SOL), anionic nanoparticles (Moxi
      ANP) and cationic nanoparticles (Moxi-CNP) were investigated. A fourfold increase
      in the relative bioavailability was observed with the Moxi-CNP (AUC(0-->t),
      3.14microg h/ml) compared with Moxi-SOL (AUC(0-->t), 0.79microg h/ml) and Moxi
      ANP (AUC(0-->t), 0.72microg h/ml) formulation. The results indicate that the
      cationic nanoparticle increases ocular bioavailability of moxifloxacin and
      prolong its residence time in the eye.

PMID- 20045277
TI  - Having it both ways.

PMID- 20045278
TI  - 5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in
      Unstable coronary Syndromes) trial a randomized comparison of an early invasive
      versus selective invasive management in patients with non-ST-segment elevation
      acute coronary syndrome.
AB  - OBJECTIVES: We present the 5-year clinical outcomes according to treatment
      strategy with additional risk stratification of the ICTUS (Invasive versus
      Conservative Treatment in Unstable coronary Syndromes) trial. BACKGROUND: Long
      term outcomes may be relevant to decide treatment strategy for patients
      presenting with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) and
      elevated troponin T. METHODS: We randomly assigned 1,200 patients to an early
      invasive or selective invasive strategy. The outcomes were the composite of death
      or myocardial infarction (MI) and its individual components. Risk stratification
      was performed with the FRISC (Fast Revascularization in InStability in Coronary
      artery disease) risk score. RESULTS: At 5-year follow-up, revascularization rates
      were 81% in the early invasive and 60% in the selective invasive group.
      Cumulative death or MI rates were 22.3% and 18.1%, respectively (hazard ratio
      [HR]: 1.29, 95% confidence interval [CI]: 1.00 to 1.66, p = 0.053). No difference
      was observed in mortality (HR: 1.13, 95% CI: 0.80 to 1.60, p = 0.49) or MI (HR:
      1.24, 95% CI: 0.90 to 1.70, p = 0.20). After risk stratification, no benefit of
      an early invasive strategy was observed in reducing death or spontaneous MI in
      any of the risk groups. CONCLUSIONS: In patients presenting with NSTE-ACS and
      elevated troponin T, we could not demonstrate a long-term benefit of an early
      invasive strategy in reducing death or MI. (Invasive versus Conservative
      Treatment in Unstable coronary Syndromes [ICTUS]; ISRCTN82153174).

PMID- 20045279
TI  - The narrative-autobiographical approach in the group education of adolescents
      with diabetes: a qualitative research on its effects.
AB  - OBJECTIVE: To introduce a narrative-autobiographical approach in the care and
      education of adolescents with type-1 diabetes and observe the effects of this
      novel approach on adolescents' self-awareness, concern for self-care, and well
      being. METHODS: Ninety-four adolescents with type-1 diabetes attending one 9-day
      summer camp in 2004, 2005, or 2006 participated in structured daily self-writing
      proposals on diabetes, integrated with daily interactive self-management
      education. After some months, we sent participants interview-like questionnaires,
      and two independent researchers performed a qualitative analysis of the 50
      answers that were mailed back. RESULTS: Writing about the discovery of diabetes
      was, for many, a stressful experience, but with a strong liberating effect. One
      relevant point was change, which occurred: (a) in the perception of self; (b) in
      the relationship with others; (c) in the relationship with the disease.
      CONCLUSIONS: The integration of autobiography in diabetes camps, by adding the
      value of sharing individual stories to the liberating power of self-writing, can
      allow the adolescents to overcome their feelings of diversity, and can initiate
      several changes reflecting increased self-efficacy, maturity, acceptance of the
      disease and responsibility in self-management. PRACTICE IMPLICATIONS: Self
      writing is feasible and well accepted, and provides healthcare professionals a
      proper way to patient-centered care.

PMID- 20045280
TI  - The role of HIV nursing consultants in the care of HIV-infected patients in Dutch
      hospital outpatient clinics.
AB  - OBJECTIVE: In the Netherlands HIV nursing consultants have participated in HIV
      care since 1985; their profession has changed with developments in HIV-treatment
      over time. The study goal was to gather information about their role in HIV-care
      and to provide an useful example to other (HIV-)care settings over the world.
      METHODS: Interviews were held with HIV nursing consultants from all AIDS
      treatment centres. Descriptive analyses and statistical tests to detect
      differences between centres categorized by care model
      (parallel/unstructured/alternating), were performed. RESULTS: 58% centres perform
      substitution of care. HIV nursing consultants see almost all patients at least
      once a year and see all patients when treatment is started/altered. The frequency
      of consultations for HIV-patients in stable condition varies, 2-4 times a year.
      Substitution leads to a slight, non-significant decrease in number of
      consultations. Adherence support is provided at the start of and during
      treatment. Regular patient discussions are common. All respondents are acquainted
      with the guidelines. Detailed knowledge of the adherence issues is limited: 58.3%
      had read the adherence chapter. CONCLUSION: Substitution of care model is an
      appropriate and effective method for the management of HIV-infected patients.
      PRACTICE IMPLICATIONS: Further development of and research into this new role of
      HIV nurse consultants is appropriate.

PMID- 20045281
TI  - [First steps towards a comparative evaluation of the French medical schools].
AB  - CONTEXT: AERES has achieved the first comparative study of the French medical
      schools based on the analysis of both teaching performance and research activity.
      METHODS: The human resources considered in the evaluation are full-time, tenured,
      university hospital teaching staff (TUHT), professors or lecturers, and are
      meaningful only if the number of students is considered. The estimated number of
      students is based on the Numerus Clausus (NC), number of students allowed each
      year to enter in the second year of medical studies. Teaching performance of each
      faculty is based on the success of their students in a national ranking
      examination (Examen Classant National - ECN), at the end of their second cycle of
      medical studies which allows them to choose, for their third specialising cycle
      of medical studies, the specialty and region of practice. Research activity is
      estimated on the SIGAPS score of the medical school based on the number and
      impact factor of the scientific papers produced for five years running by the
      full-time professors and lecturers of each medical school, the number of national
      clinical research projects (PHRC) they have conducted during the three past years
      and the number of research units headed by these professors labelled by CNRS and
      INSERM. RESULTS: French medical school characteristics are markedly different in
      the number of university-hospital teaching staff, teaching performances and
      research activities. Numerous teaching staff and labelled research units have a
      beneficial influence on research activity and teaching results. The impact on
      teaching results is less statistically significant than that on research
      activity. A medical school mapping is then outlined. PROSPECT: More precise
      analysis of the observed differences between medical schools will allow propose
      recommendations.

PMID- 20045282
TI  - Endovascular management of complex splenic aneurysm with the "amplatzer" embolic
      platform: application of cone-beam computed tomography.

PMID- 20045283
TI  - Clinicopathological study and treatment outcomes of 121 cases of ameloblastomas.
AB  - The aim of this paper is to evaluate the clinical, radiographic, and
      histopathological findings and treatment modalities in all cases of
      ameloblastomas treated at the Sao Paulo Cancer Hospital, between 1953 and 2003.
      121 case reports were retrieved from the medical files. Data were reviewed and
      statistical analysis was performed using Kaplan-Meyer method and Cox proportional
      risk model. The patients' age ranged from 2 to 82 years (mean 33.2 years), with a
      slight female prevalence. Most cases were located in the posterior mandible
      (80%). Radiographically, 60% showed a multilocular pattern. 113 casees were solid
      ameloblastomas, and plexiforme subtype was the most common. Solid tumours were
      treated by wide resection, curettage and criosurgery, or curettage alone, and
      unicystic tumours by curettage and/or cryotherapy. The global mean recurrence
      rate was 22%, with a mean follow-up of 9.7 years. The ameloblastomas were
      predominantly solid, affecting the posterior mandible. Important factors for
      outcome were radiographically multilocular lesions, the presence of ruptured
      basal cortical bone and histologically follicular tumours.

PMID- 20045284
TI  - Life cycle of human melanocytes is regulated by endothelin-1 and stem cell factor
      in synergy with cyclic AMP and basic fibroblast growth factor.
AB  - BACKGROUND: Although the function of human melanocytes is well characterized at
      cellular and molecular levels, the mechanism of the regulation of the life cycle
      (proliferation, differentiation, and cell death) of human melanocytes is not
      fully understood. OBJECTIVE: This study aims to clarify what factors are involved
      in regulating the life cycle of human melanocytes using serum-free culture
      system. METHODS: Human epidermal melanocytes were cultured in a serum-free growth
      medium supplemented with several kinds of growth factors, cytokines, and hormones
      and the effects of these factors on the life cycle of melanocytes were
      investigated in detail. RESULTS: Of the factors tested, endothelin-1 (ET-1)
      stimulated the proliferation of melanoblasts and melanocytes in the presence of
      cyclic AMP (cAMP)-elevating factor such as dibutyryl cAMP (DBcAMP) and of basic
      fibroblast growth factor (bFGF). ET-1 also stimulated the proliferation and
      differentiation of human melanocytes in the presence of DBcAMP. Moreover, stem
      cell factor (SCF) stimulated the proliferation of melanoblasts and melanocytes
      synergistically with ET-1. The removal of ET-1 and SCF from the culture medium
      greatly inhibited the proliferation of melanocytes followed by apoptotic cell
      death. CONCLUSION: These results suggest that the life cycle of human melanocytes
      is regulated by ET-1 and SCF in synergy with cAMP and bFGF.

PMID- 20045285
TI  - Variability of polymyxin B major components in commercial formulations.

PMID- 20045286
TI  - Typing of vancomycin-resistant enterococci obtained from patients at Danish
      hospitals and detection of a genomic island specific to CC17 Enterococcus
      faecium.

PMID- 20045287
TI  - Rifaximin-induced alteration of virulence of diarrhoea-producing Escherichia coli
      and Shigella sonnei.
AB  - Rifaximin shortens the duration of travellers' diarrhoea without important
      alteration of colonic flora. This study investigated the expression of virulence
      factors [heat-stable (ST) and heat-labile (LT) enterotoxins, surface adhesion
      factors (CS2/CS3, CS6) and matrix metalloproteinase-9 (MMP-9)] as well as the
      interleukin (IL)-8 induction potential of diarrhoeagenic Escherichia coli and
      Shigella sonnei strains exposed to rifaximin (8, 32 and 64mg/L) for 4, 8, 18 and
      24h. Following exposure to rifaximin, enterotoxigenic E. coli (ETEC) isolates did
      not express ST/LT, CS2/CS3 or CS6, whereas enteroaggregative E. coli (EAEC) and
      S. sonnei isolates did not produce detectable amounts of MMP-9. Moreover,
      induction of IL-8 was undetectable. At subinhibitory concentrations, rifaximin
      alters the virulence of ETEC, EAEC and S. sonnei isolates. These findings help
      explain the efficacy of rifaximin despite minimal alteration of colonic flora.

PMID- 20045288
TI  - Purification, characterisation and identification of acidocin LCHV, an
      antimicrobial peptide produced by Lactobacillus acidophilus n.v. Er 317/402
      strain Narine.
AB  - In the last two decades, antimicrobial peptides (AMPs) have been gaining
      attention as antimicrobial alternatives to chemical food preservatives and
      commonly used antibiotics. Lactobacillus acidophilus n.v. Er 317/402 strain
      Narine produces a small AMP with a molecular weight of 1.1kDa, designated
      acidocin LCHV. In this study, the AMP was extremely heat stable (90min at 130
      degrees C), was active over a wide pH range and was found to be sensitive to
      proteolytic enzymes (trypsin, pepsin and proteinase K). Acidocin LCHV has a broad
      spectrum of activity both against Gram-positive and Gram-negative pathogens,
      including several that are classified as Especially Dangerous Infections by the
      World Health Organization as well as meticillin-resistant Staphylococcus aureus
      (MRSA) and Clostridium difficile. Matrix-assisted laser desorption/ionisation
      time-of-flight mass spectrometry (MALDI-TOF/MS) was used to determine the
      molecular mass and sequence of the purified peptide. Complete killing with
      immediate impact on cells was observed within a very short period of time
      (10min).

PMID- 20045290
TI  - Fluoroquinolone resistance of Pseudomonas aeruginosa isolates causing nosocomial
      infection is correlated with levofloxacin but not ciprofloxacin use.
AB  - This study investigated the correlation between fluoroquinolone (ciprofloxacin or
      levofloxacin) use and rates of fluoroquinolone resistance in Pseudomonas
      aeruginosa isolates from patients with nosocomial infection at a medical centre
      in Taiwan. Antibiotic utilisation data were extracted on a monthly basis from the
      inpatient pharmacy computer system records from January 2003 to December 2008.
      Fluoroquinolone use was expressed as defined daily dose per 1000 patient-days and
      was correlated with rates of fluoroquinolone-resistant P. aeruginosa every 6
      months. Regression analysis was performed to explore the relationship between
      ciprofloxacin and levofloxacin use (both parenteral and oral forms) and
      resistance of P. aeruginosa isolates. During the study period, the susceptibility
      of P. aeruginosa to fluoroquinolones decreased after increasing use of
      fluoroquinolones, and increased after decreasing use of levofloxacin. Parenteral
      levofloxacin use was significantly positively correlated with resistance of P.
      aeruginosa to ciprofloxacin (P=0.015) and fluoroquinolones (either ciprofloxacin
      or levofloxacin, P=0.014). Use of both parenteral and oral forms of levofloxacin
      was also significantly positively correlated with resistance of P. aeruginosa
      isolates to ciprofloxacin (P=0.029), levofloxacin (P=0.031) and fluoroquinolones
      (P=0.010). The total amount of ciprofloxacin (oral and parenteral) and parenteral
      ciprofloxacin use were negatively correlated with resistance of P. aeruginosa
      isolates to fluoroquinolones. However, the amounts of oral ciprofloxacin,
      parenteral levofloxacin, oral levofloxacin and total levofloxacin use were each
      positively correlated with resistance of P. aeruginosa to fluoroquinolones.
      Levofloxacin use was associated with increased resistance of P. aeruginosa to
      fluoroquinolones, whereas ciprofloxacin use did not have a significant impact on
      fluoroquinolone resistance rates.

PMID- 20045289
TI  - Meropenem monotherapy is as effective as and safer than imipenem to treat brain
      abscesses.
AB  - The efficacy of carbapenems versus cefotaxime (8g/day)+metronidazole (1.5-2g/day)
      [combined standard chemotherapy (CSC)] for the treatment of brain abscess was
      compared. Fifty-nine adult patients with brain abscesses received either imipenem
      or meropenem (3-4g/day) or CSC for a mean of 5 weeks, in addition to neurosurgery
      in most cases. Cure was obtained in 84.7% of cases; 42/47 (89.4%) on carbapenems
      [18/22 (81.8%) on imipenem versus 24/25 (96.0%) on meropenem] and 8/12 (66.7%) on
      CSC (P=0.06). Seven patients with multiple abscesses were treated with imipenem
      (1 died; cure rate 85.7%), five with meropenem (all survived; cure rate 100%) and
      five with CSC (2 died; cure rate 60%) (P<0.4). Neurosurgery was performed in
      43/59 cases (72.9%); 17 (77.3%) in the imipenem group, 21 (84.0%) in the
      meropenem group and 5 (41.7%) in the CSC group (P=0.02). There was no significant
      difference in the rate of relapse requiring re-intervention. Treatment with
      meropenem was associated with a lower mortality than CSC (P=0.026). Seizures were
      observed only with carbapenems [8/22 (36.4%) for imipenem versus 2/25 (8.0%) for
      meropenem; P=0.03]. Carbapenems were more effective than CSC for treatment of
      brain abscesses. Because meropenem induced significantly fewer seizures than
      imipenem with at least the same clinical efficacy, the former appears to be a
      better choice to treat this infection.

PMID- 20045291
TI  - Activity of tigecycline against multidrug-resistant clinical isolates of
      Clostridium spp. from Europe.

PMID- 20045292
TI  - Severe and refractory Clostridium difficile infection successfully treated with
      tigecycline and metronidazole.

PMID- 20045293
TI  - Safety and efficacy of intravenous colistin (colistin methanesulphonate) for
      severe multidrug-resistant Gram-negative bacterial infections.
AB  - Multidrug-resistant (MDR) bacterial infections are increasing in Taiwan
      hospitals, prompting the common use of colistin. In this study, the safety and
      efficacy of intravenous (i.v.) colistin was assessed. The medical records of
      patients receiving colistin for treatment of MDR Gram-negative bacterial
      infections between January 2006 and September 2008 at a Taiwan medical centre
      were reviewed retrospectively. Demographics, clinical presentation, causative
      organism, adverse events and outcomes were recorded. Of the 115 patient records
      analysed, 74 patients (64%) were treated in the Intensive Care Unit. Common
      underlying diseases were hypertension (49%), chronic pulmonary disease (46%),
      chronic kidney disease (33%) and malignancy (31%). Lower respiratory tract
      infections were most common (71%), followed by primary bloodstream infections
      (12%), urinary tract infections (8.7%) and others (7.8%). Successful treatment
      with i.v. colistin against MDR Gram-negative bacterial infections occurred in 59
      patients (51%). Multivariate analysis showed that a higher Acute Physiology and
      Chronic Health Evaluation (APACHE) II score (odds ratio=1.14; 95% confidence
      interval 1.02-1.28; P=0.02) was independently associated with a poor clinical
      response. Overall, 12 (14%) of 84 patients presented nephrotoxicity and 4
      patients (3.5%) had neurotoxicity. In conclusion, colistin is an effective
      antimicrobial agent for severe infections caused by MDR Gram-negative bacteria.
      Clinical outcomes are associated with the severity of infection and underlying
      diseases. Compared with previous reports, this study showed a lower incidence of
      nephrotoxicity and neurotoxicity.

PMID- 20045294
TI  - Interaction of antimicrobial peptide s-thanatin with lipopolysaccharide in vitro
      and in an experimental mouse model of septic shock caused by a multidrug
      resistant clinical isolate of Escherichia coli.
AB  - s-thanatin, an analogue of thanatin, was synthesised by substituting the
      fifteenth amino acid threonine with serine and showed broad antimicrobial
      activity against Gram-negative and Gram-positive bacteria. To evaluate its
      antimicrobial activity against a multidrug-resistant (MDR) clinical isolate as
      well as its anti-endotoxin activity, its lipopolysaccharide (LPS)-binding and 
      neutralising activity in vitro and its therapeutic efficacy in an experimental
      model of septic shock caused by a MDR clinical isolate of Escherichia coli were
      studied. The ability of s-thanatin to bind or neutralise LPS from E. coli O111:B4
      was determined using a quantitative assay kit. Male ICR mice were given an
      intraperitoneal (i.p.) administration of 2x10(10) colony-forming units of E. coli
      E79466. Following bacterial challenge, all animals were randomised to receive
      i.p. administration of saline, 40mg/kg ceftazidime (CAZ), or 40mg/kg CAZ+s
      thanatin (10, 20 or 40mg/kg). The results showed that s-thanatin not only
      completely bound to the LPS (median effective concentration of 17.5microg/mL) but
      also improved the survival and reduced the number of inoculated bacteria in a
      mouse model of septic shock. s-thanatin may be an attractive candidate to develop
      as an anti-MDR bacterial agent.

PMID- 20045295
TI  - Correlations between (51)V solid-state NMR parameters and chemical structure of
      vanadium (V) complexes as models for related metalloproteins and catalysts.
AB  - The parameters describing the quadrupolar and CSA interactions of 51V solid-state
      MAS NMR investigations of model complexes mimicking vanadoenzymes as well as
      vanadium containing catalysts and enzyme complexes are interpreted with respect
      to the chemical structure. The interpretation is based on the data of 15 vanadium
      complexes including two new complexes with previously unpublished data and 13
      complexes with data previously published by us. Correlations between the chemical
      structure and the 51V solid-state NMR data of this class of compounds have been
      established. Especially for the isotropic chemical shift delta(iso) and the
      chemical shift anisotropy delta(sigma), correlations with specific structural
      features like the coordination number of the vanadium atom, the number of
      coordinating nitrogens, the number of oxygen atoms and the chemical surrounding
      of the complex could be established for these compounds. Moreover, quantitative
      correlations between the solid-state NMR parameters and specific bond angles and
      bond lengths have been obtained. Our results can be of particular interest for
      future investigations concerning the structure and the mode of action of related
      vanadoenzymes and vanadate protein assemblies, including the use of vanadate
      adducts as transition state analogs for phosphate metabolizing systems.

PMID- 20045296
TI  - Fluorescence and circular dichroism studies of conjugates between metsulfuron
      methyl and human serum albumin.
AB  - Metsulfuron-methyl is a sulfonylurea herbicide widely used for broad-leaved weed
      control in cereals. The binding interaction between metsulfuron-methyl and human
      serum albumin was elucidated by fluorescence, circular dichroism and molecular
      modeling. The results showed that the alterations of albumin secondary structure
      in the presence of herbicide induced the slight unfolding of the polypeptide
      chain of albumin. Fluorescence data revealed that the fluorescence quenching of
      albumin by herbicide was the result of the formation of the albumin-herbicide
      complex and hydrophobic and hydrogen bonds interactions were the dominant
      intermolecular force in stabilizing the complex. Fluorescence probes studies
      implied that the binding of herbicide to albumin primarily took place in
      subdomain IIA (Sudlow's site I), and this also corroborates with molecular
      modeling simulations. This study highlights for the first time the binding
      mechanism, specific binding site and binding region of herbicide on albumin at
      the first time. Therefore, this investigation enriches our information of the
      interaction of sulfonylurea herbicide to the physiologically protein albumin.

PMID- 20045297
TI  - Protein adsorption on poly(N-isopropylacrylamide)-modified silicon surfaces:
      effects of grafted layer thickness and protein size.
AB  - In this work, we investigated the protein adsorption on the end-tethered
      thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes with varying
      grafted layer thickness prepared via surface-initiated atom transfer radical
      polymerization (SI-ATRP) on initiator-immobilized silicon surfaces. The thickness
      of a grafted layer was modulated by adjusting reaction time and/or solvent
      composition. The surface properties as a function of thickness were investigated
      by water contact angle, X-ray photoelectron spectroscopy (XPS), and atomic force
      microscope (AFM). The influence of PNIPAAm-grafted layer thickness on human serum
      albumin (HSA) adsorption in phosphate-buffered saline (PBS) (pH 7.4) at different
      temperature was evaluated using a radiolabeling method. In a lower thickness
      range (<15 nm), protein adsorption on PNIPAAm-grafted layer shows a
      thermoresponsive change in a certain extent, but the variation is not remarkable.
      However, it is interesting to observe that these surfaces exhibit good protein
      resistant property. For the surface with a PNIPAAm thickness of 13.4 nm, the HSA
      adsorption level measured at room temperature was approximately 7 ng/cm2,
      corresponding to a reduction of 97% compared to the unmodified silicon surface.
      For thicker PNIPAAm-grafted surface with thickness of 38.1 nm, the adsorption
      results of three proteins (HSA, fibrinogen, and lysozyme) with different sizes
      and charges indicate that the PNIPAAm-modified surface exhibits a size-sensitive
      property of protein adsorption.

PMID- 20045299
TI  - Artificial intelligence in biomedical engineering and informatics: an
      introduction and review.

PMID- 20045298
TI  - [Acute motor deficit in childhood: diagnosis management].
AB  - Acute motor deficit is not uncommon in childhood, with various neurological
      etiologies. Pertinent semiological analysis allows correct diagnosis management,
      with adequate paraclinical investigations. The authors describe this clinical
      diagnosis strategy. The most common clinical situations and various etiologies
      are presented; paraclinical investigations confirming the diagnosis are
      discribed, with specific attention to central nervous system imaging according to
      the most recent sequences.

PMID- 20045300
TI  - Is there a role for adjuvant hysterectomy after suboptimal concurrent
      chemoradiation in cervical carcinoma?
AB  - AIMS: Failure to carry out intracavitary brachytherapy (ICBT) in cervical
      carcinoma results in suboptimal chemoradiation and increases the risk of
      recurrence. The aim of this study was to investigate the role of adjuvant
      hysterectomy after unsuccessful ICBT. MATERIALS AND METHODS: A retrospective
      analysis was carried out of all women referred with cervical carcinoma between
      January 1999 and July 2007 where ICBT insertion was unsuccessful after the
      initial chemoradiation. The data collected and analysed included histology, stage
      of disease, causes for unsuccessful ICBT insertion, the response to the initial
      chemoradiation, subsequent treatment, morbidity, recurrence rates and survival
      rates. Kaplan-Meier and Log-rank methods were used to analyse recurrence-free and
      overall survival rates. RESULTS: ICBT insertion was unsuccessful in 19 of 208
      (9%) patients. The causes of failure were: inability to dilate the cervix;
      uterine perforation; vesicovaginal fistula; patient refusal; other problems,
      including the presence of pyometrium, patient not fit for general anaesthetic,
      and narrow vagina; and consultant choice with no obvious reason. Fourteen of 19
      patients (74%) received further pelvic external beam radiotherapy (EBRT) alone;
      five (26%) patients underwent adjuvant hysterectomy. The median follow-up for all
      patients was 63 months; 60 months for patients treated with adjuvant hysterectomy
      (range 31-68 months) and 85 months for patients treated with further EBRT. None
      of the patients treated with adjuvant hysterectomy developed any significant late
      toxicity. Seven patients (50%) treated with EBRT have relapsed compared with none
      in the adjuvant hysterectomy arm (P=0.068). Six patients (43%) in the EBRT arm
      have subsequently died of recurrent disease compared with none in the adjuvant
      hysterectomy arm (P=0.152). CONCLUSIONS: Adjuvant hysterectomy after unsuccessful
      ICBT does not seem to increase late toxicity and reduces the risk of pelvic
      recurrence and may improve survival. The role of adjuvant hysterectomy after
      suboptimal chemoradiation merits further investigation in clinical trials.

PMID- 20045301
TI  - Frequency of opioid use in a population of cancer patients during the trajectory
      of the disease.
AB  - AIMS: Bearing in mind that Denmark has one of the world's highest legal uses of
      strong opioids per capita, the aim of the present study was to describe the
      frequency of opioid use in a complete, population-based cohort of cancer patients
      at different time points during the trajectory of the disease, and to analyse the
      influence of different factors on opioid use close to death. MATERIALS AND
      METHODS: All incident cancer patients registered in 1997-1998 (n=4006) from a
      population of 470,000 were followed individually from diagnosis to death (non
      survivors) or for 5 years (survivors). The use of opioids was obtained from a
      prescription database covering the whole population. RESULTS: Among the 43%
      cancer patients who survived for 5 years, 12% used opioids at diagnosis, 38%
      during follow-up and 10% after 5 years. For the non-survivors, 80% used opioids
      sometime during follow-up. At diagnosis, use related inversely to the cancer
      type's 5-year survival, and ranged from 20 to 46%; before death 64-76% used
      opioids. The odds ratios for opioid use at death were smaller for breast cancer
      (0.53; confidence interval 0.33-0.85), haemopoietic cancer (0.28; confidence
      interval 0.17-0.44) and the group of miscellaneous cancers (0.54; confidence
      interval 0.36-0.83) compared with colorectal cancer. Older age, longer disease
      duration and male gender (0.76; confidence interval 0.59-0.99) reduced the odds
      of opioid use at death. CONCLUSIONS: Judged by the use of opioids, moderate to
      severe pain is frequent throughout the trajectory of the cancer disease. The
      frequency of opioid use was in accordance with the frequency of moderate to
      severe cancer-related pain described in published studies. This completely
      population-based data set enables analyses of the actual practice regarding
      cancer patients' use of opioids, and it can serve as a more effective template
      for the management of cancer pain than the traditional measures, such as opioid
      consumption per capita, for international comparisons.

PMID- 20045302
TI  - Connecting autophagy to senescence in pathophysiology.
AB  - Cellular senescence is an extremely stable form of cell cycle arrest activated in
      response to stress. Autophagy, a lysosome-dependent cellular catabolic process,
      can also be triggered by cellular stresses. Both senescence and autophagy have
      been implicated in a similar range of pathophysiologies, including cancer, aging
      and age-related symptoms. Senescence is a heterogeneous phenotype that is
      composed of multiple effector mechanisms and autophagy was recently identified as
      a new effector of senescence. Autophagy seemingly has different impacts on cells
      responding to stress through a diversity of effects: recycling of metabolic
      waste, cell survival and protein expression regulation.

PMID- 20045303
TI  - Necroptosis as an alternative form of programmed cell death.
AB  - The family of death receptors plays a critical role in regulating cell number and
      eliminating harmful or virally infected cells. Agonistic stimulation of death
      receptors is known to lead two alternative cell fates by either activating NF
      kappaB to promote cell survival or inducing apoptosis to lead to cell death; and
      now a third pathway, termed necroptosis or programmed necrosis has been
      identified. Interestingly, a death-domain containing kinase, RIP1, is involved in
      mediating all three pathways, with its kinase activity specifically involved in
      regulating necroptosis. The availability of necrostatin-1, a specific inhibitor
      of RIP1 kinase, made it possible to dissect the distinct functional domains of
      RIP1. Recent genome-wide siRNA screens have identified multiple players of
      necroptosis that may interact with and/or regulate RIP1 kinase and mediate the
      signaling pathway and execution of necroptosis. Necroptosis and necrostatins
      provide an exciting new opportunity for developing new treatments for multiple
      human diseases involving necrosis and inflammation.

PMID- 20045304
TI  - Cytoprotective roles for autophagy.
AB  - Macroautophagy (referred to as autophagy in this review) is a genetically
      regulated bulk degradation program conserved from yeast to humans, in which
      cytoplasmic substrates, such as damaged organelles and long-lived proteins, are
      delivered to lysosomes for degradation. In this review, we consider recent data
      that highlight possible mechanisms whereby autophagy mediates cytoprotective
      effects. These include the ability of autophagy to buffer against starvation,
      protect against apoptotic insults and clear mitochondria, aggregate-prone
      proteins and pathogens. These effects are pertinent to the roles of autophagy in
      normal human physiology, including the early neonatal period and ageing, as well
      as a variety of diseases, including cancer, neurodegenerative conditions and
      infectious diseases.

PMID- 20045305
TI  - Hydrolysis of organic matter during autoclaving of commingled household waste.
AB  - Commingled household waste (HW) that had a controlled composition was autoclaved
      at elevated pressures in the presence of saturated steam for one hour at the
      nominal temperature levels of 130 degrees C, 160 degrees C and 200 degrees C. The
      focus of this study was the impact of temperature/pressure on hydrolysis of
      organic matter during autoclaving and the extent of its hydrolysis. The pH
      decreased with autoclaving temperature with which it had a linear relationship,
      and ranged from 7.4 and 6 in floc, and 6.7 and 3.6 in steam condensate. Overall,
      organic matter solubilisation, as indicated by dissolved organic carbon,
      biological and chemical oxygen demands, and total dissolved solids, increased
      with temperature. Lignin did not appear to hydrolyse. Hemicellulose hydrolysed
      and degraded the most, followed by cellulose. The highest recoveries of
      hemicellulose and cellulose in solution were achieved at 160 degrees C, although
      the latter could be due to experimental error. The largest losses of
      hemicellulose and cellulose were recorded at 200 degrees C. The performance of
      the system in respect to hydrolysis was inferior compared to other hydrothermal
      systems, particularly those employing wet oxidation.

PMID- 20045306
TI  - Accelerated carbonation of different size fractions of bottom ash from RDF
      incineration.
AB  - This paper investigates the effects of accelerated carbonation on the
      characteristics of bottom ash from refuse derived fuel (RDF) incineration, in
      terms of CO(2) uptake, heavy metal leaching and mineralogy of different particle
      size fractions. Accelerated aqueous carbonation batch experiments were performed
      to assess the influence of operating parameters (temperature, CO(2) pressure and
      L/S ratio) on reaction kinetics. Pressure was found to be the most relevant
      parameter affecting the carbonation yield. This was also found to be largely
      dependent on the specific BA fraction treated, with CO(2) uptakes ranging from
      approximately 4% for the coarse fractions to approximately 14% for the finest
      one. Carbonation affected both the mineralogical characteristics of bottom ash,
      with the appearance of neo-formation minerals, and the leaching behaviour of the
      material, which was found to be mainly related to the change upon carbonation in
      the natural pH of the ash.

PMID- 20045307
TI  - Probing the interaction of a membrane receptor with a surface-attached ligand
      using whole cells on acoustic biosensors.
AB  - Two different types of acoustic sensors, a surface acoustic wave device
      supporting a Love-wave (Love-SAW) and a quartz crystal microbalance system with
      dissipation (QCM-D), were used to demonstrate the potential of acoustic devices
      to probe the binding of a cell membrane receptor to an immobilized ligand. The
      class I Major Histocompatibility Complex molecule HLA-A2 on the surface of whole
      cells and anti-HLA monoclonal antibodies immobilized on the sensor were used as
      an interaction pair. Acoustic measurements consisted of recording the energy and
      velocity or frequency of the acoustic wave. Results showed that both devices
      could detect the number of cells in solution as well as the cells bound to the
      surface. In addition, the Love-wave sensor, which can sense binding events within
      the relatively short distance of approximately 50 nm from the device surface, was
      sensitive to the number of bonds formed between the cell membrane and the device
      surface while the QCM-D, which can sense deeper within the liquid, was found to
      respond well to stimuli that affected the cell membrane rigidity (cytochalasin D
      treatment). The above results suggest that acoustic biosensors can be a powerful
      tool in the study of cell/substrate interactions and acoustic devices of
      different type can be used in a complementary way.

PMID- 20045308
TI  - The improvement of glucose bioelectrocatalytic properties of platinum electrodes
      modified with electrospun TiO2 nanofibers.
AB  - Pt electrodes have been modified with electrospun titanium dioxide (TiO(2))
      nanofibers with controllable densities for electrochemical detection. The TiO(2)
      nanofiber/Pt electrodes show excellent electrocatalytic activity to electro
      oxidation of hydrogen peroxide and the response current density to an addition of
      hydrogen peroxide is 30% higher than that for a Pt electrode. Glucose oxidase
      (GOx) molecules have been effectively immobilized on the surface of the TiO(2)
      nanofibers and the resulted chitosan/GOx/TiO(2) nanofiber/Pt electrodes with a
      optimum density of nanofibers exhibit excellent glucose bioelectrocatalytic
      performance including good amperometric current response (9.25 microA cm(-2)mM(
      1)), short response time (10s) and low detection limit (0.01 mM). We have found
      that the nanofibers modified on the Pt electrode improved the sensitivity of the
      enzyme electrode to glucose for 2.7 times and extended the detection limit by one
      order of magnitude in comparison with flat Pt electrodes. It is expected that
      electrodes modified with electrospun TiO(2) nanofibers will find more promising
      applications in high performance electrochemical biosensors.

PMID- 20045309
TI  - Expression and prognostic significance of the inhibitor of apoptosis protein
      (IAP) family and its antagonists in chronic lymphocytic leukaemia.
AB  - Impaired apoptosis is still considered to be an important event in the
      development and progression of chronic lymphocytic leukaemia (CLL). However,
      mechanisms of this defect have not been fully elucidated. In this study,
      expression of inhibitor of apoptosis proteins, IAPs (cIAP1, cIAP2, XIAP and
      survivin), and their antagonists (Smac/DIABLO and HtrA2/Omi) was comprehensively
      analysed in 100 untreated CLL patients, using flow cytometry and Western blot
      techniques. Expression of anti-apoptotic cIAP1 and cIAP2 in leukaemic cells was
      significantly higher than in non-tumour lymphocytes (p=0.000001 and p=0.014,
      respectively), whereas the IAP-antagonist, Smac/DIABLO, was decreased in CLL
      (p=0.010). Higher expression of all analysed IAPs (cIAP1, p=0.002; cIAP2,
      p=0.026; XIAP, p=0.002; survivin, p=0.00006) and lower levels of Smac/DIABLO
      (p=0.006) were found in patients with progressive disease, compared to those with
      stable CLL. High baseline expression of cIAP1 and survivin correlated with worse
      response to treatment. Co-expression of these proteins was associated with
      shorter overall survival of CLL patients (p=0.005). In conclusion, CLL cells show
      the apoptosis-resistant profile of IAPs/IAP-antagonist expression. Upregulation
      of IAPs is associated with a progressive course of the disease. Co-expression of
      cIAP1 and survivin seems to be an unfavourable prognostic factor in CLL patients.
      Further studies with longer follow up are warranted to confirm and expand these
      findings.

PMID- 20045310
TI  - Chemotherapy-Induced Peripheral Neurotoxicity assessment: a critical revision of
      the currently available tools.
AB  - Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a frequent, potentially
      severe and dose-limiting side-effect of cancer treatment. Despite its clinical
      relevance that limits the use of several antineoplastic agents and even the
      future development of new anticancer drugs, several crucial aspects of CIPN
      remain unsolved, one of which is how to assess its occurrence and severity in the
      most effective and reliable way. CIPN severity is generally assessed using Common
      Toxicity Criteria (CTC) scales, although it is well known that significant inter
      observer disagreement exists using these scales. Moreover, most CTC scores mix
      impairment, disability and quality of life measures, which could lead to
      misinterpretation of the results and unpredictable under- or overestimation of
      the effect. This uncertainty may lead to different interpretations of the results
      of the same clinical trials by clinicians and also by regulatory agencies. The
      use of other types of scale based on clinical and instrumental examinations, or
      the use of self-administered questionnaires for patients, has not yet really
      improved the accuracy of CIPN assessment, although some of these tools are
      promising and deserve to be further validated. As a result, there is a general
      recognition that CIPN has still not been properly assessed and that improvements
      should be made. In this review, the available data regarding the different tools
      used to assess CIPN will be revised and their features will be critically
      examined, with a special focus on their reliability and reproducibility across
      examiners and, when available, through direct comparison.

PMID- 20045311
TI  - Clinical assessment of patients with advanced non-small-cell lung cancer eligible
      for second-line chemotherapy: a prognostic score from individual data of nine
      randomised trials.
AB  - PURPOSE: Knowledge of prognostic factors for advanced non-small-cell lung cancer
      (NSCLC) patients eligible for second-line treatment is scarce. The aim of this
      study was to assess the prognostic role of a number of routinely collected
      clinical variables and to provide a summary index to discriminate patients
      according to probability of survival. METHODS: Individual data from nine
      randomised trials of second-line treatment in advanced NSCLC were analysed.
      Primary end-point was overall survival (OS). Cox model, stratified by trial, was
      used for multivariate analyses, and a prognostic index was provided and validated
      according to an internal/external procedure. RESULTS: Out of 1239 patients, 1197
      patients (97%) had complete information. Median OS was 7.4months. At multivariate
      analysis, prognosis was significantly influenced by gender (worse in males),
      performance status (PS), tumour histology (worse in squamous and other histology
      versus adenocarcinoma), stage (worse in IV versus IIIB), type of previous
      treatment (worse for patients pretreated with platinum) and response to first
      line (worse for patients not obtaining objective response). Prognostic score
      values range from 0 to 14. When three categories were derived, median overall
      survival values were equal to 11.6, 7.5 and 3.0months for best (<5), intermediate
      (5-9) and worst (>9) categories, respectively. CONCLUSION: Prognosis of patients
      eligible for second-line treatment of advanced NSCLC is significantly conditioned
      by gender, PS, histology, stage, previous use of platinum and response to first
      line. A prognostic score was derived that discriminates well subjects with a
      relatively more favourable prognosis and those with very short life expectancy.

PMID- 20045312
TI  - Sludge treatment wetlands: a review on the state of the art.
AB  - Sludge management has become a key issue in wastewater treatment, representing
      some 20-60% of the operational costs of conventional wastewater treatment plants.
      The high water content of the sludge results in large daily flow rates to be
      handled and treated. Thus, the search for methods to improve sludge volume
      reduction continues to be of major interest. The technology known as sludge
      treatment wetlands has been used for sludge dewatering since the late 1980s.
      Major advantages include its low energy requirements, reduced operating and
      maintenance costs, and a reasonable integration in the environment. However, the
      number of plants in operation is still low in comparison with conventional
      technologies. This study represents a review of the state of the art of sludge
      treatment wetlands. The main characteristics and operational aspects of the
      technology are described, including a summary of the main results reported in the
      literature. Finally, the efficiency of sludge treatment wetlands versus
      conventional treatments is compared.

PMID- 20045313
TI  - Second-generation bioethanol from eucalypt sulphite spent liquor.
AB  - The spent liquor from acidic sulphite pulping of Eucalyptus globulus (HSSL) is
      the side product from sulphite pulp production and besides sulphonated lignin
      contains sugars from degraded hemicelluloses, mainly pentoses. Pichia stipitis
      fermentation of these sugars for bioethanol production was the primary goal of
      this work. The increasing of HSSL proportion in fermentation media affected
      negatively the ethanol yield. Thus with 20% of HSSL (v/v) attained maximum
      ethanol yield was 0.15 g of ethanol by g of sugar consumed (g(e) g(s)(-1)) and
      with 60% (v/v) only 0.08 g(e) g(s)(-1). Biological removal of acetic acid from
      HSSL improved fermentation though the complete removal of acetic acid and
      polyphenolics (including sulphonated species) by treatment with ion-exchange
      resins was required for highly successful bioethanol production. Accordingly, the
      fermentative metabolic pathway of P. stipitis has been promoted allowing fair
      ethanol productivity and yield (Yp/s = 0.49 g(e) g(s)(-1)) at relatively low
      maximum of cell growth rate (micro(max) = 0.21 h(-1)).

PMID- 20045314
TI  - Study on poly-hydroxyalkanoate (PHA) production in pilot scale continuous mode
      wastewater treatment system.
AB  - Generation of poly-hydroxyalkanoates (PHAs) from milk and ice-cream processing
      wastewater was studied in a continuous mode reactor system at pilot scale. The
      integrated system comprised an anaerobic acidogenic reactor (AAR), a conventional
      activated sludge production reactor (ASPR) and a PHA synthesis reactor (PHAR) to
      induce PHA accumulation in the biomass which was finally harvested while treating
      the raw dairy wastewater to meet the disposal limits thereby reducing generation
      of disposable sludge. The PHA content in the PHA rich biomass was approximately
      43% of the sludge dry weight. Kinetics of both ASPR and PHAR were studied. The
      maximum PHA yield coefficient (Y(sp)(max)) with respect to COD degradation in the
      PHAR was derived as 0.25 kg PHA/kg of COD degraded. Similarly, the kinetic
      parameters i.e. K(s), micro(m), Y(obs) and k(d) of the ASPR were 37.16 mg/l COD,
      0.97 d(-1), 0.51 mg MLSS/mg COD and 0.049 d(-1), respectively.

PMID- 20045315
TI  - Discovery and SAR of substituted 3-oxoisoindoline-4-carboxamides as potent
      inhibitors of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer.
AB  - Through conformational restriction of a benzamide by formation of a seven
      membered hydrogen-bond with an oxindole carbonyl group, a series of PARP
      inhibitors was designed for appropriate orientation for binding to the PARP
      surface. This series of compounds with a 3-oxoisoindoline-4-carboxamide core
      structure, displayed modest to good activity against PARP-1 in both intrinsic and
      cellular assays. SAR studies at the lactam nitrogen of the pharmacophore have
      suggested that a secondary or tertiary amine is important for cellular potency.
      An X-ray structure of compound 1e bound to the protein confirmed the formation of
      a seven-membered intramolecular hydrogen bond. Though revealed previously in
      peptides, this type of seven-membered intramolecular hydrogen bond is rarely
      observed in small molecules. Largely due to the formation of the intramolecular
      hydrogen bond, the 3-oxoisoindoline-4-carboxamide core structure appears to be
      planar in the X-ray structure. An additional hydrogen bond interaction of the
      piperidine nitrogen to Gly-888 also contributes to the binding affinity of 1e to
      PARP-1.

PMID- 20045316
TI  - Bicyclic peptides as potent inhibitors of histone deacetylases: optimization of
      alkyl loop length.
AB  - Bicyclic tetrapeptide hydroxamic acids were prepared as histone deacetylase
      (HDAC) inhibitors, and the evaluated inhibitory activity shows that they are
      potent against HDAC1 and HDAC4. The in vivo activity depends on alkyl loop
      length.

PMID- 20045317
TI  - Pharmacophore modeling and virtual screening for designing potential 5
      lipoxygenase inhibitors.
AB  - Inhibitors of the 5-Lipoxygenase (5-LOX) pathway have a therapeutic potential in
      a variety of inflammatory disorders such as asthma. In this study, chemical
      feature based pharmacophore models of inhibitors of 5-LOX have been developed
      with the aid of HipHop and HypoGen modules within Catalyst program package. The
      best quantitative pharmacophore model, Hypo1, which has the highest correlation
      coefficient (0.97), consists of two hydrogen-bond acceptors, one hydrophobic
      feature and one ring aromatic feature. Hypo1 was further validated by test set
      and cross validation method. The application of the model shows great success in
      predicting the activities of 65 known 5-LOX inhibitors in our test set with a
      correlation coefficient of 0.85 with a cross validation of 95% confidence level,
      proving that the model is reliable in identifying structurally diverse compounds
      for inhibitory activity against 5-LOX. Furthermore, Hypo1 was used as a 3D query
      for screening Maybridge and NCI databases within catalyst and also drug like
      compounds obtained from Enamine Ltd, which follow Lipinski's rule of five. The
      hit compounds were subsequently subjected to filtering by docking and
      visualization, to identify the potential lead molecules. Finally 5 potential lead
      compounds, identified in the above process, were evaluated for their inhibitory
      activities. These studies resulted in the identification of two compounds with
      potent inhibition of 5-LOX activity with IC(50) of 14 microM and 35 microM,
      respectively. These studies thus validate the pharmacophore model generated and
      suggest the usefulness of the model in screening of various small molecule
      libraries and identification of potential lead compounds for 5-LOX inhibition.

PMID- 20045318
TI  - Discovery of cyclicsulfonamide derivatives as 11 beta-hydroxysteroid
      dehydrogenase 1 inhibitors.
AB  - A new series of cyclic sulfonamide derivatives was synthesized and evaluated for
      their ability to inhibit 11beta-HSD1. Cyclic sulfonamides with phenylacetyl
      substituents at the 2-position showed nanomolar inhibitory activities. Among
      them, compound 4e exhibited a good in vitro inhibitory activity and selectivity
      toward human 11beta-HSD2.

PMID- 20045319
TI  - Anti-influenza diarylheptanoids from the bark of Alnus japonica.
AB  - This study to investigate anti-influenza components from the bark of Alnus
      japonica resulted in the isolation of two rare acylated diarylheptanoids, named
      oregonoyl A (5) and oregonoyl B (6), along with nine known compounds (1-4 and 7
      11). Their structures were elucidated on the basis of extensive spectroscopic and
      chemical methods. Antiviral testing of compounds 1-11 against KBNP-0028 (H9N2)
      avian influenza virus showed that platyphyllone (10) was strongly active, and
      platyphyllonol-5-xylopyranoside (9) was moderately active against KBNP-0028 as
      compared with the positive control, zanamivir, respectively.

PMID- 20045320
TI  - Phenylacetic acid regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2
      one pharmacophore: evaluation as dual inhibitors of cyclooxygenases and 5
      lipoxygenase with anti-inflammatory activity.
AB  - A novel class of phenylacetic acid regioisomers possessing a N-difluoromethyl-1,2
      dihydropyrid-2-one pharmacophore attached to its C-2, C-3 or C-4 position was
      designed for evaluation as anti-inflammatory (AI) agents. A number of compounds
      exhibited a combination of potent in vitro cyclooxygenase-2 (COX-2) and 5
      lipoxygenase (5-LOX) inhibitory activities. 2-(1-Difluoromethyl-2-oxo-1,2
      dihydropyridin-4-yl)phenylacetic acid (9a) exerted the most potent AI activity
      among this group of compounds. Molecular modeling studies showed that the N
      difluoromethyl-1,2-dihydropyridin-2-one moiety present in 9a inserts into the
      secondary pocket present in COX-2 to confer COX-2 selectivity, and that the N
      difluoromethyl-1,2-dihydropyrid-2-one group (9a) binds close to the region of the
      15-LOX enzyme containing catalytic iron (His361, His366). Accordingly, the N
      difluoromethyl-1,2-dihyrdopyrid-2-one moiety possesses properties that make it an
      attractive pharmacophore suitable for the design of dual COX-2/5-LOX inhibitory
      AI drugs.

PMID- 20045321
TI  - An octahydro-cyclopenta[c]pyrrole series of inhibitors of the type 1 glycine
      transporter.
AB  - We describe a novel series of inhibitors of the type 1 glycine transporter
      (GlyT1) as an approach to relieving the glutamatergic deficit that is thought to
      underlie schizophrenia. Synthesis and SAR follow-up of a series of octahydro
      cyclopenta[c]pyrrole derivatives afforded potent in vitro inhibition of GlyT1 as
      well as in vivo activity in elevating CSF glycine. We also found that a 3-O(c
      pentyl), 4-F substituent may serve as a surrogate for the widely used 3
      trifluoromethoxy group, suggesting its application as an isostere for future
      medicinal chemistry studies.

PMID- 20045322
TI  - Design, synthesis and studies of triphosphate analogues for the production of
      anti AZT-TP antibodies.
AB  - Triphosphates anabolites are the active chemical species of nucleosidic reverse
      transcriptase inhibitors in HIV-therapy. Herein, we describe (i) the design of
      stable triphosphate analogues of AZT using molecular modelling, (ii) their
      synthesis and (iii) their use for producing anti AZT-TP antibodies in the aim of
      developing an immunoassay for therapeutic drug monitoring.

PMID- 20045323
TI  - Fluorescent analysis of excess electron transfer through DNA.
AB  - The DNA base stack provides unique features for the efficient long-range charge
      transfer. For the purpose of investigating excess electron transfer process
      through DNA, we developed a new method for fluorescence analysis of excess
      electron transfer based on reductive cleavage of a disulfide bond and a thiol
      specific fluorescent probe. Excess electron transfer was detected by monitoring
      the fluorescence of emissive pyrene monomer generated by the reaction of pyrene
      maleimides with the cleaved disulfide bond (thiols). Mechanism of reductive
      cleavage of disulfides through excess electron transfer and subsequent reaction
      with the fluorescent probes were discussed. This facile and sensitive detection
      by fluorescence method can be applied for mechanistic study of excess electron
      transfer.

PMID- 20045324
TI  - Sec24-dependent secretion drives cell-autonomous expansion of tracheal tubes in
      Drosophila.
AB  - Epithelial tubes in developing organs, such as mammalian lungs and insect
      tracheae, need to expand their initially narrow lumina to attain their final,
      functional dimensions. Despite its critical role for organ function, the cellular
      mechanism of tube expansion remains unclear. Tracheal tube expansion in
      Drosophila involves apical secretion and deposition of a luminal matrix, but the
      mechanistic role of secretion and the nature of forces involved in the process
      were not previously clear. Here we address the roles of cell-intrinsic and
      extrinsic processes in tracheal tube expansion. We identify mutations in the
      sec24 gene stenosis, encoding a cargo-binding subunit of the COPII complex. Via
      genetic-mosaic analyses, we show that stenosis-dependent secretion drives tube
      expansion in a cell-autonomous fashion. Strikingly, single cells autonomously
      adjust both tube diameter and length by implementing a sequence of events
      including apical membrane growth, cell flattening, and taenidial cuticle
      formation. Known luminal components are not required for this process. Thus, a
      cell-intrinsic program, rather than nonautonomous extrinsic cues, controls the
      dimensions of tracheal tubes. These results indicate a critical role of membrane
      associated proteins in the process and imply a mechanism that coordinates
      autonomous behaviors of individual cells within epithelial structures.

PMID- 20045325
TI  - Requirement for an enzymatic visual cycle in Drosophila.
AB  - BACKGROUND: The visual cycle is an enzymatic pathway employed in the vertebrate
      retina to regenerate the chromophore after its release from light-activated
      rhodopsin. However, a visual cycle is thought to be absent in invertebrates such
      as the fruit fly Drosophila melanogaster. RESULTS: We demonstrate that an
      enzymatic visual cycle exists in flies for chromophore regeneration and requires
      a retinol dehydrogenase, PDH, in retinal pigment cells. Absence of PDH resulted
      in progressive light-dependent loss of rhodopsin and retinal degeneration. These
      defects are suppressed by introduction of a mammalian dehydrogenase, RDH12, which
      is required in humans to prevent retinal degeneration. We demonstrate that a
      visual cycle is required in flies to sustain a visual response under nutrient
      deprivation conditions that preclude de novo production of the chromophore.
      CONCLUSIONS: Our results demonstrate that an enzymatic visual cycle exists and is
      required in flies for maintaining rhodopsin levels. These findings establish
      Drosophila as an animal model for studying the visual cycle and retinal diseases
      associated with chromophore regeneration.

PMID- 20045326
TI  - Identical skin toxins by convergent molecular adaptation in frogs.
AB  - The Tree of Life is rife with adaptive convergences at all scales and biological
      levels of complexity. However, natural selection is not likely to result in the
      independent evolution of identical gene products. Here we report such a striking
      example of evolutionary convergence in the toxic skin secretions of two distantly
      related frog lineages. Caeruleins are important decapeptides in pharmacological
      and clinical research [1] and are commonly believed to represent a single
      evolutionary class of peptides [2-4]. Instead, our phylogenetic analyses
      combining transcriptome and genome data reveal that independently evolved
      precursor genes encode identical caeruleins in Xenopus and Litoria frogs. The
      former arose by duplication from the cholecystokinin (cck) gene, whereas the
      latter was derived from the gastrin gene. These hormone genes that are involved
      in many physiological processes diverged early in vertebrate evolution, after a
      segmental duplication during the Cambrian period. Besides implicating convergent
      mutations of the peptide-encoding sequence, recurrent caerulein origins entail
      parallel shifts of expression from the gut-brain axis to skin secretory glands.
      These results highlight extreme structural convergence in anciently diverged
      genes as an evolutionary mechanism through which recurrent adaptation is attained
      across large phylogenetic distances.

PMID- 20045327
TI  - A complete mtDNA genome of an early modern human from Kostenki, Russia.
AB  - The recovery of DNA sequences from early modern humans (EMHs) could shed light on
      their interactions with archaic groups such as Neandertals and their
      relationships to current human populations. However, such experiments are highly
      problematic because present-day human DNA frequently contaminates bones [1, 2].
      For example, in a recent study of mitochondrial (mt) DNA from Neolithic European
      skeletons, sequence variants were only taken as authentic if they were absent or
      rare in the present population, whereas others had to be discounted as possible
      contamination [3, 4]. This limits analysis to EMH individuals carrying rare
      sequences and thus yields a biased view of the ancient gene pool. Other
      approaches of identifying contaminating DNA, such as genotyping all individuals
      who have come into contact with a sample, restrict analyses to specimens where
      this is possible [5, 6] and do not exclude all possible sources of contamination.
      By studying mtDNA in Neandertal remains, where contamination and endogenous DNA
      can be distinguished by sequence, we show that fragmentation patterns and
      nucleotide misincorporations can be used to gauge authenticity of ancient DNA
      sequences. We use these features to determine a complete mtDNA sequence from a
      approximately 30,000-year-old EMH from the Kostenki 14 site in Russia.

PMID- 20045328
TI  - Transcription-dependent cytosine deamination is a novel mechanism in ultraviolet
      light-induced mutagenesis.
AB  - Skin cancer is the most ubiquitous cancer type in the Caucasian population, and
      its incidence is increasing rapidly [1]. Transcribed proliferation-related genes
      in dermal stem cells are targets for the induction of ultraviolet light (UV)
      induced mutations that drive carcinogenesis. We have recently found that
      transcription of a gene increases its mutability by UV in mammalian stem cells,
      suggesting a role of transcription in skin carcinogenesis [2]. Here we show that
      transcription-associated UV-induced nucleotide substitutions are caused by
      increased deamination of cytosines to uracil within photolesions at the
      transcribed strand, presumably at sites of stalled transcription complexes.
      Additionally, via an independent mechanism, transcription of UV-damaged DNA
      induces the generation of intragenic deletions. We demonstrate that transcription
      coupled nucleotide excision repair (TC-NER) provides protection against both
      classes of transcription-associated mutagenesis. Combined, these results unveil
      the existence of two mutagenic pathways operating specifically at the transcribed
      DNA strand of active genes. Moreover, these results uncover a novel role for TC
      NER in the suppression of UV-induced genome aberrations and provide a rationale
      for the efficient induction of apoptosis by stalled transcription complexes.

PMID- 20045329
TI  - "Singing on the wing" as a mechanism for species recognition in the malarial
      mosquito Anopheles gambiae.
AB  - Anopheles gambiae, responsible for the majority of malaria deaths annually, is a
      complex of seven species and several chromosomal/molecular forms. The complexity
      of malaria epidemiology and control is due in part to An. gambiae's remarkable
      genetic plasticity, enabling its adaptation to a range of human-influenced
      habitats. This leads to rapid ecological speciation when reproductive isolation
      mechanisms develop [1-6]. Although reproductive isolation is essential for
      speciation, little is known about how it occurs in sympatric populations of
      incipient species [2]. We show that in such a population of "M" and "S" molecular
      forms, a novel mechanism of sexual recognition (male-female flight-tone matching
      [7-9]) also confers the capability of mate recognition, an essential precursor to
      assortative mating; frequency matching occurs more consistently in same-form
      pairs than in mixed-form pairs (p = 0.001). [corrected] Furthermore, the key to
      frequency matching is "difference tones" produced in the nonlinear vibrations of
      the antenna by the combined flight tones of a pair of mosquitoes and detected by
      the Johnston's organ. By altering their wing-beat frequencies to minimize these
      difference tones, mosquitoes can match flight-tone harmonic frequencies above
      their auditory range. This is the first description of close-range mating
      interactions in incipient An. gambiae species.

PMID- 20045330
TI  - Transcriptional orchestration of the regulated secretory pathway in neurons by
      the bHLH protein DIMM.
AB  - BACKGROUND: The Drosophila basic helix-loop-helix (bHLH) gene dimmed (dimm)
      promotes a neurosecretory/neuroendocrine phenotype in cells but is not associated
      with specific neuropeptides or neurohormones. Rather, it is expressed by those
      peptidergic neurons that project long axons and appear to produce large amounts
      of secretory peptides. Here, we genetically transform nonpeptidergic neurons in
      Drosophila to study DIMM's action mechanisms. RESULTS: Nonpeptidergic neurons
      normally fail to accumulate ectopic neuropeptides. We now show that they will do
      so when they are also forced to express ectopic DIMM. Furthermore, mass
      spectrometry shows that photoreceptors, which are normally nonpeptidergic, fail
      to process an ectopic neuropeptide precursor to make bioactive peptides but will
      do so efficiently when DIMM is co-misexpressed. Likewise, photoreceptors, which
      normally package the fast neurotransmitter histamine within small clear synaptic
      vesicles, produce numerous large dense-core vesicles (LDCVs) when they misexpress
      DIMM. These novel LDCVs accumulate ectopic neuropeptide when photoreceptors co
      misexpress a neuropeptide transgene. DIMM-expressing photoreceptors no longer
      accumulate histamine and lose synaptic organelles critical to their normal
      physiology. CONCLUSIONS: These findings indicate that DIMM suppresses
      conventional fast neurotransmission and promotes peptidergic neurosecretory
      properties. We conclude that DIMM normally provides a comprehensive
      transcriptional control to direct the differentiation of dedicated neuroendocrine
      neurons.

PMID- 20045332
TI  - Do the organic sulfur compounds DMSP and DMS drive coral microbial associations?
AB  - Dimethylsulfoniopropionate (DMSP) and dimethylsulfide (DMS) are key compounds in
      the global sulfur cycle. Moreover, DMS is particularly important in climate
      regulation owing to its role in cloud formation. Reef building corals are major
      contributors to the production of these two compounds and also form diverse and
      complex associations with bacteria, which are known to play a crucial role in the
      degradation of DMSP and DMS. Here, we highlight an extensive overlap between
      bacterial species implicated in DMSP/DMS degradation and those associated with
      corals, leading to the hypothesis that these two compounds play a major role in
      structuring coral-associated bacterial communities, with important consequences
      for coral health and the resilience of coral reefs. We also explore the
      publically available metagenome databases and show that genes implicated in DMSP
      metabolism are abundant in the viral component of coral-reef-derived metagenomes,
      indicating that viruses can act as a reservoir for such genes.

PMID- 20045333
TI  - Comment on "an assessment of the predictors of difficult intubation in patients
      with acromegaly".

PMID- 20045331
TI  - Intermediate filaments take the heat as stress proteins.
AB  - Intermediate filament (IF) proteins and heat shock proteins (HSPs) are large
      multimember families that share several features, including protein abundance,
      significant upregulation in response to a variety of stresses, cytoprotective
      functions, and the phenocopying of several human diseases after IF protein or HSP
      mutation. We are now coming to understand that these common elements point to IFs
      as important cellular stress proteins with some roles akin to those already well
      characterized for HSPs. Unique functional roles for IFs include protection from
      mechanical stress, whereas HSPs are characteristically involved in protein
      folding and as chaperones. Shared IF and HSP cytoprotective roles include
      inhibition of apoptosis, organelle homeostasis, and scaffolding. In this report,
      we review data that corroborate the view that IFs function as highly specialized
      cytoskeletal stress proteins that promote cellular organization and homeostasis.

PMID- 20045334
TI  - The soluble major histocompatibility complex class I-related chain A protein
      reduced NKG2D expression on natural killer and T cells from patients with
      prolactinoma and non-secreting pituitary adenoma.
AB  - This study analyses aspects of the immune system in prolactinoma and non
      secreting pituitary adenoma. Serum soluble major histocompatibility complex class
      I-related chain A protein (sMICA) concentrations were measured by enzyme-linked
      immunosorbent assay. NKG2D-expressing natural killer and T cells were analyzed by
      flow cytometry. A correlation analysis was also performed to associate sMICA
      levels with NKG2D expression. The expression of MICA was examined in specific
      tissues by use of the reverse transcription-polymerase chain reaction. A
      significant amount of sMICA was detected in the serum of nearly all patients. We
      found decreased percentage and mean fluorescence intensity of NKG2D-expressing
      natural killer and T cells from patients with prolactinoma and non-secreting
      pituitary adenoma compared to those from healthy donors. Pearson analysis showed
      a negative correlation between sMICA and NKG2D-expressing cells. The immune
      escape of pituitary adenoma is related to the down-regulation of NKG2D and the up
      regulation of its ligand MICA.

PMID- 20045335
TI  - Comment on "association between mild parkinsonian signs and mortality in an
      elderly male cohort in China".

PMID- 20045337
TI  - Synthesis and structure-activity relationship of 1,2,4-triazole-containing
      diarylpyrazolyl carboxamide as CB1 cannabinoid receptor-ligand.
AB  - Numerous research groups have been engaged in searching for novel CB1 receptor
      antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, proved to
      be efficacious in human for the treatment of obesity. In the present study, a
      series of 1,2,4-triazole-containing diarylpyrazolyl carboxamides based on the 1,5
      diarylpyrazole template of rimonabant, was synthesized and tested for CB1
      receptor binding affinity. The structure-activity relationship studies
      demonstrated that incorporation of 1,2,4-triazole ring onto the pyrazole scaffold
      via a methylene linker led to a significant improvement for CB1 receptor binding
      affinity. Importantly, these analogues also exhibited excellent selectivity for
      CB1 receptor over CB2 receptor.

PMID- 20045338
TI  - Proteasome inhibition in human breast cancer cells with high catechol-O
      methyltransferase activity by green tea polyphenol EGCG analogs.
AB  - A pro-drug 8 of a synthetic analog 7 is more active in its antiproliferative
      activity against human breast cancer MDA-MB-231 cells possessing high catechol-O
      methyltransferase (COMT) activity than the pro-drugs of EGCG and the analog 5.
      The higher activity of 8 is attributed to it not being a substrate of COMT.

PMID- 20045339
TI  - Design, synthesis and SAR analysis of novel selective sigma1 ligands (Part 2).
AB  - In order to investigate the molecular features involved in sigma receptors (sigma
      Rs) binding, new compounds based on arylalkylaminoalcoholic, arylalkenyl- and
      arylalkylaminic scaffolds were synthesized and their affinity towards sigma(1)-
      and sigma(2)-Rs subtypes was evaluated. The most promising compounds were also
      screened for their affinity at micro-opioid, delta-opioid and kappa-opioid
      receptors. Biological results are herein presented and discussed.

PMID- 20045340
TI  - Study of the influence of the liquid scintillator in the Compton efficiency
      tracing method.
AB  - The principle of the Compton source efficiency tracing method (CET) in liquid
      scintillation counting (LSC) is to use, as a tracer, a Compton electron source
      temporarily created inside the source being measured. The tracer source and the
      source to measure have thus exactly the same chemical composition. A main
      advantage anticipated for this measurement method is its low sensitivity to the
      kB factor and insensitivity to the chemical composition and quenching of the
      source, which would obviate the necessity to develop a reference liquid
      scintillator cocktail in the framework of an international reference system for
      the measurement of pure-beta emitters by LSC. We took the opportunity of a
      tritiated water international activity measurement in comparison to prepare LS
      sources using various commercial liquid scintillator cocktails. Tritium is
      assumed to be a good candidate for testing the LSC activity measurement method,
      as the detection efficiency is rather low and the effect of the ionization
      quenching parameter, kB, on the detection efficiency calculation by the TDCR
      method is known to be important. The sources were measured using a TDCR counter
      equipped with a Compton spectrometer in order to apply the CET method. The
      measurements are analyzed using both the TDCR method and CET method in order to
      deduce the optimal calculation parameters. The detection efficiency range covered
      by these experiments is from 0.4 to 0.6, allowing a good test of the validity of
      the physical assumptions included in the calculation model. The paper will
      conclude on the advantages and drawbacks of using this CET method in the
      framework of an international reference system for low-energy pure-beta
      radionuclides.

PMID- 20045341
TI  - Irradiation of 4''x4'' NaI(Tl) detector by the 14 MeV neutrons.
AB  - Within the EURopean Illicit TRAfficking Countermeasures Kit (EURITRACK) project,
      a new Tagged Neutron Inspection System (TNIS) has been developed and installed in
      the Port of Rijeka in Croatia. The system was based on the examination of sea
      containers with the 14 MeV neutron beam. During the operation the characteristic
      gamma rays were produced and measured by several 5''x5''x10'' NaI(Tl) detectors.
      During this procedure some of the detectors were exposed to an intensive neutron
      beam radiation. It was necessary to check for possible radiation damage of the
      NaI(Tl) scintillator during the gamma detector selection phase of the project.
      The 4''x4'' NaI(Tl) detector was exposed to 14 MeV neutrons for 20 h. From the
      presented results on energy resolution and activation measurements it could be
      concluded that there are no significant differences in energy resolution before
      and after the irradiation by 4.7x10(11) of 14 MeV neutrons. The only problem
      could be the high level of medium and long term induced activity in the energy
      region below 2 MeV.

PMID- 20045342
TI  - Standardization and measurement of gamma-ray probability per decay of 177Lu.
AB  - The procedure followed by the Nuclear Metrology Laboratory (LMN), at the Nuclear
      and Energy Research Institute (IPEN), for the primary standardization of (177)Lu
      is described. This radionuclide is widely used in radiopharmacy due to its
      convenient half-life and emitted beta ray energies. The (177)Lu solution was
      supplied during an international comparison sponsored by BIPM in 2009 and the
      primary standardization has been accomplished by the 4pibeta-gamma coincidence
      method using a proportional counter in 4pi geometry coupled with two NaI(Tl)
      scintillation counters. The beta efficiency was varied by placing Collodion and
      aluminum absorbers over and under the radioactive source. The (177)Lu calibrated
      sources were also measured in a previously calibrated HPGe spectrometer, in order
      to obtain the emission probability per decay for the selected gamma-ray
      transitions. The experimental extrapolation curves were also compared with Monte
      Carlo simulations by means of code ESQUEMA developed at the LMN.

PMID- 20045343
TI  - Calculation of the effective dose from natural radioactivity in soil using MCNP
      code.
AB  - Effective dose delivered by photon emitted from natural radioactivity in soil was
      calculated in this work. Calculations have been done for the most common natural
      radionuclides in soil (238)U, (232)Th series and (40)K. A ORNL human phantoms and
      the Monte Carlo transport code MCNP-4B were employed to calculate the energy
      deposited in all organs. The effective dose was calculated according to ICRP 74
      recommendations. Conversion factors of effective dose per air kerma were
      determined. Results obtained here were compared with other authors.

PMID- 20045344
TI  - Evaluation of procedures for determination of Ra-226 in water by alpha-particle
      spectrometry with emphasis on the recovery.
AB  - Radium-226 is one of the best known long-lived alpha-emitters abundantly present
      in the environment. The determination of radium isotopes in environmental samples
      usually requires a demanding chemical separation before measurement and
      quantification. Each step in the chemical separation process can involve losses
      of the analyte, therefore it is of vital importance that the recovery of the
      whole radiochemical procedure is evaluated. The emphasis of the work presented
      was determination of the chemical recovery using the different yield tracers Ra
      223, Ra-225 and Ba-133.

PMID- 20045345
TI  - Early and late prognostic significance of remote and reversible preoperative
      neurological events in patients undergoing coronary artery bypass grafting.
AB  - OBJECTIVES: Preoperative neurological event with functional impairment is high
      risk for operative morbidity and mortality after coronary artery bypass grafting
      (CABG). However, data regarding the influence of remote and reversible
      neurological events on early and late survival are lacking. METHODS: The clinical
      profile and operative outcome of 5542 patients who underwent first-time CABG from
      01 April 1999 through 30 June 2008 were analysed. Late survival data were 100%
      complete. The relationship between preoperative neurological event and survival
      (early and late) was investigated using multivariate logistic regression and
      survival analyses. RESULTS: Mean age was 65.2+/-9.2 years, and 494 patients
      (8.9%) had remote reversible neurological events preoperatively. There were 129
      (2.3%) operative and 595 (10.7%) late deaths after a mean follow-up of 4.9+/-2.7
      years. Reversible neurological events had strong univariate (odds ratio (OR)
      2.80, 95% confidence interval (CI) 1.82-4.33, p<0.0001) and multivariate
      associations (OR 2.14, 95% CI 1.34-3.41, p=0.001) with operative mortality.
      Although reversible neurological events exhibited a powerful univariate
      relationship with late deaths (hazard ratio (HR) 1.66, 95% CI 1.30-2.12,
      p<0.0001), this was not maintained after controlling for other factors in
      multivariable analysis (HR 1.24, 95% CI 0.97-1.59, p=0.08). Neurological
      complications, more frequent in patients with preoperative events, were
      implicated in 25% of operative deaths in patients with preoperative neurological
      events. The respective 5- and 10-year survival rates for patients with reversible
      neurological events (86% and 68%) were substantially lower than others (91% and
      80%, p<0.0001). CONCLUSIONS: Remote reversible neurological events increase the
      risk of fatal and non-fatal postoperative neurological complications. Rigorous
      measures to improve cerebral protection are warranted in these patients.

PMID- 20045346
TI  - Low incidence of malignancy in heart-transplant recipients in Taiwan: an update
      and comparison with kidney-transplant recipients.
AB  - OBJECTIVE: Malignancy is the leading cause of death among heart-transplant
      recipients. There is a higher incidence of post-transplant malignancy in heart
      transplant recipients than in kidney-transplant recipients. This study sought to
      assess the incidence of malignancy in heart-transplant recipients in Taiwan.
      METHODS: This is a retrospective chart review. RESULTS: From 1987 to 2008, 291
      patients who underwent heart transplantation and survived for more than 1 month
      were enrolled. Seventeen patients (5.8%) developed de novo malignancies including
      skin cancers (three), post-transplant lymphoproliferative diseases (seven) and
      solid-organ malignancies (seven). Solid-organ malignancies affected prostate,
      liver, urinary bladder, kidney, lung, larynx, pancreas and brain in seven
      patients. Malignancy was responsible for 7% and 13% of all death for heart
      transplant recipients who lived for more than 1 year and more than 5 years. The
      cumulative incidence of 1.03% at 1 year, 4.2% at 5 years and 8.1% at 10 years in
      our patients was much lower than the incidences reported in the multicentre
      registry of the International Society for the Heart and Lung Transplantation and
      in the Western series. The incidence was especially low for skin cancers.
      Compared with previous reports of kidney-transplant recipients in Taiwan, the
      incidence of post-transplant malignancy was not significantly increased.
      CONCLUSIONS: The incidence of post-transplant malignancy was low in Chinese heart
      transplant recipients compared with heart-transplant recipients in Western
      countries. It resulted from a relative rarity of skin cancers in the Chinese
      population.

PMID- 20045347
TI  - A scale for decision making between whole lung transplantation or lobar
      transplantation.
AB  - OBJECTIVE: In lung transplantation, appropriate size matching is of crucial
      importance to achieve satisfactory outcomes. Tailoring of the lung has been
      repeatedly described as successful means of overcoming size disparities. The goal
      of this study was to define a parameter helping the surgeon in the decision
      whether a standard lung transplantation or a lobar transplantation should be
      anticipated. METHODS: We retrospectively analysed the ratio between donor total
      lung capacity (TLC) and recipient TLC in all lung-transplant procedures performed
      in our institution from 1 January 2008 to 30 November 2008. The utility of this
      ratio using predicted recipient TLC (D/pR index) and real recipient TLC (D/rR
      index) in discriminating between whole lung transplantation and lobar
      transplantation was studied with the receiver operating characteristic (ROC)
      analysis. RESULTS: The median D/pR index in whole lung transplantations was 1.01
      (range: 0.69-1.26) and 1.19 in lobar transplantation (range: 1.09-1.54). In the
      range between 1.12 and 1.14, sensitivity and specificity are both above 90%. The
      area under the ROC curve for D/pR index was 0.96. The median D/rR index in whole
      lung transplantations was 0.95 (range: 0.56-2.74) and 1.58 in lobar
      transplantation (range: 0.85-2.56). The area under the ROC curve was 0.73.
      CONCLUSIONS: We conclude that the D/pR index is more useful than D/rR index in
      discriminating between whole lung transplantation and lobar transplantation. With
      an area under the ROC curve of 0.96, this seems to be a suitable indicator in
      deciding between whole lung transplantation and lobar transplantation.

PMID- 20045348
TI  - Valve surgery in octogenarians: does it prolong life?
AB  - OBJECTIVES: Age-related degenerative heart-valve disease is a health issue in the
      present era. Octogenarians are frequently affected by concomitant diseases and,
      with the present lack of resources, the risk/benefit of valvular replacement
      therapy poses serious medical, economical and political challenge. We analysed
      the long-term survival of 346 octogenarians who underwent 352 operations between
      1 January 1987 and 1 January 2009 and we compared it with the survival of the
      general population, matched for age, sex and operative year. METHODS: The total
      follow-up was of 1352 years, maximum 15.7 years and was nearly complete except
      for a single foreigner. Heart diseases, concomitant pathologies, complications
      and actuarial survival of this study group were compared with 4649 younger
      counterparts, who received 5416 operations during the same time frame.
      Octogenarians were sorted by age, sex and operative year and the expected
      survival was calculated by applying US survival rate and added to the Kaplan
      Meier plot for visual comparison. RESULTS: A total of 279 aortic, 38 mitral and
      35 mitro-aortic valves were replaced or repaired using 357 bioprostheses, 18
      mechanical prostheses, 12 reparative operations and 24 re-operations. A total of
      75% of patients were younger than 84 years, 95% were younger than 87 years and
      99% younger than 90 years. Sex prevalence was 215 female versus 131 male.
      Operative (30 days) mortality was 5.5% and overall survival was 84.3% at 1 year,
      65.4% at 5 years, 27.3% at 10 years and 5.4% at 15 years. The expected survival
      of the age-, sex-, operative year-matched population was 26.9% at 10 years and
      7.9% at 15 years. Female operative mortality was 5.9% and survival was
      respectively 86.3%, 70.2%, 27.5% and 9.1%, male mortality was 4.5% and survival
      was respectively 81%, 56.7%, 28.8% and 0% (p=0.16). Expected female survival was
      30% at 10 years and 10% at 15 years versus 22% and 5.6%, respectively, in males.
      Six octogenarians underwent re-operation, with one death. CONCLUSIONS: Despite
      the highest prevalence of concomitant diseases and the requirement of additional
      resources for the detection and neutralisation of risk factors, heart-valve
      operations in octogenarians offer excellent results that compare favourably with
      the expected survival of the age-, sex- and operative year-matched population,
      particularly after primary operations.

PMID- 20045349
TI  - Abnormal immunity and stem/progenitor cells in acquired aplastic anemia.
AB  - Acquired aplastic anemia (AA) is considered as an immune-mediated bone marrow
      failure syndrome, characterized by hypoplasia and pancytopenia with fatty bone
      marrow. Abnormal immunity is the major factor mediating the pathogenesis of
      acquired AA. Activated DCs might promote the polarization to Th1 cells, and
      activate CD8(+) T cells. A variety of immune molecules including IFN-gamma, TNF
      alpha, MIP-1alpha and IL-2, 8, 12, 15, 17, 23, produced by them and stromal
      cells, compose a cytokine network to destruct stem/progenitor cells as well as
      hematopoietic stem/progenitor cells, mesenchymal stem cells (MSCs) and
      angioblasts/endothelial progenitor cells. Inversely, deficient MSCs,
      CD4(+)CD25(+) T cells, NK cells, NKT cells and early hematopoietic growth factors
      diminish the capacity of immune regulation and the support of hematopoiesis. As a
      result, stem/progenitor cells are significantly impaired to be disabled cells
      with markedly deficient proliferation, differentiation, induced apoptosis and
      dysfunctional response to growth factor stimuli, together with rare normal ones.
      Although some patients can be ameliorated by stem-cell transplantation or
      immunosuppressive therapy, more effective and convenient therapies such as
      patient-specific pluripotent iPS cells based on definite pathogenesis are
      expected.

PMID- 20045350
TI  - Generation of mouse macrophages expressing membrane-bound TNF variants with
      selectivity for TNFR1 or TNFR2.
AB  - Tumor necrosis factor-alpha (TNF) is expressed on the cell surface as a
      transmembrane form (tmTNF), that can be released as a soluble form (solTNF) via
      proteolytic cleavage. These two types of TNF exert their biological functions by
      binding to one of two TNF receptors, TNFR1 or TNFR2. However, the biological
      function of tmTNF through these two receptors remains to be determined. Here, we
      generated macrophages that expressed tmTNF mutants with selectivity for either
      TNFR1 or TNRF2 as a tool to evaluate signaling through these receptors. Wild-type
      TNF (wtTNF), TNFR1-selective mutant TNF (mutTNF-R1) or TNFR2-selective mutant TNF
      (mutTNF-R2) were individually expressed on the TNFR1(-/-)R2(-/-) mouse
      macrophages (Mphi) as the tmTNF forms. tm-mutTNF-R1-expressing Mphi exhibited
      significant selectivity for binding to TNFR1, whereas tm-mutTNF-R2-expressing
      Mphi only showed a slight selectivity for binding to TNFR2. Signaling by tm
      mutTNF-R1-expressing Mphi through the hTNFR2 was weaker than that of tm-wtTNF
      expressing Mphi, suggesting that the binding selectivity correlated with
      functional selectivity. Interestingly, signaling by tm-mutTNF-R2-expressing Mphi
      through TNFR2 was much stronger than signaling by tm-wtTNF-expressing Mphi,
      whereas signaling by the corresponding soluble form was weaker than that mediated
      by wtTNF. These results indicate tmTNF variants might prove useful for the
      functional analysis of signaling through TNF receptors.

PMID- 20045351
TI  - Body fat distribution has no effect on serum visfatin levels in healthy female
      subjects.
AB  - Obesity is the presence of either abnormal absolute amount or relative proportion
      of body fat. Contrary to gluteal obesity, visceral obesity is associated with
      different metabolic alterations including insulin resistance (IR). A relatively
      new adipocytokine visfatin is shown to be expressed predominantly in visceral fat
      and exhibit insulin-mimicking effects in rodents. It is still unclear whether
      serum visfatin levels are associated with increased total or visceral fat mass in
      humans. The aim of our study was to investigate the relation between visfatin and
      obesity parameters namely body mass index (BMI) and waist circumference (WaC) and
      IR in healthy female subjects. Eighty one female subjects 20 years of age, having
      no diagnosis of glucose intolerance or diabetes, hypertension and dyslipidemia
      were chosen. The patients were divided into four groups according to their BMI
      and WaC values. Serum visfatin and HOMA-IR levels did not differ among groups. No
      correlation was detected between serum visfatin levels and obesity and metabolic
      parameters. In conclusion, we demonstrated that body fat distribution did not
      affect serum visfatin levels in healthy female subjects. Further studies are
      needed to clarify the exact factors influencing and determining serum visfatin
      levels and its clinical reflections.

PMID- 20045352
TI  - Adiponectin is required for enhancement of CCL2 expression in adipose tissue
      during Listeria monocytogenes infection.
AB  - Obesity is an important background of metabolic syndrome progression. Our
      previous study demonstrated that chemokine CCL2 expression was suppressed in
      liver of obese mice that were highly susceptible to Listeria monocytogenes
      infection. We investigated the role of adiponectin in CCL2 expression in obese
      mice after L. monocytogenes infection. When leptin-deficient obese ob/ob mice
      were infected intraperitoneally with L. monocytogenes, the elimination of
      bacteria from spleen, liver, mesenteric lymph nodes and adipose tissue was
      inhibited in ob/ob mice compared with their heterozygote littermates, ob/? mice.
      CCL2 expression in the adipose tissue of ob/? mice was enhanced by L.
      monocytogenes infection, different from ob/ob mice. Similarly, adiponectin
      expression was not observed in the adipose tissue of ob/ob mice. When mouse
      adipocyte 3T3-F442A-derived adipocytes were infected with L. monocytogenes, CCL2
      expression was transiently up-regulated, following up-regulation of adiponectin
      expression. Up-regulation of CCL2 in adipocytes by L. monocytogenes infection was
      suppressed by knocked-down of adiponectin expression and supplementation of
      recombinant adiponectin partially recovered CCL2 expression. These results
      suggest that adiponectin is required for appropriate expression of CCL2 that is
      important for macrophage recruitment in response to bacterial infection.

PMID- 20045353
TI  - The heteroplasmic m.14709T>C mutation in the tRNA(Glu) gene in two Tunisian
      families with mitochondrial diabetes.
AB  - Diabetes mellitus (DM) is a heterogeneous disorder characterized by the presence
      of chronic hyperglycemia. Genetic factors play an important role in the
      development of this disorder, and several studies reported mutations in nuclear
      genes implicated in the insulin function. Besides, DM can be maternally
      transmitted in some families, possibly due to the maternal mitochondrial
      inheritance. In fact, mitochondrial genes may be plausible causative agents for
      diabetes, since mitochondrial oxidative phosphorylation plays an important role
      in glucose-stimulated insulin secretion from beta cells. MATERIALS AND METHODS:
      In this report, we screened two Tunisian families with mitochondrial diabetes for
      the m.3243A>G and the m.14709T>C mutations, respectively, in the tRNA(Leu(UUR))
      and the tRNA(Glu) genes. RESULTS: The polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and the sequence-specific primers by
      polymerase chain reaction (SSP-PCR) analysis in the leucocytes and the buccal
      mucosa in the members of the two families showed the absence of the m.3243A>G
      mutation and the presence of the heteroplasmic m.14709T>C mutation in the
      tRNA(Glu) gene in the two tested tissues. CONCLUSIONS: We conclude that the
      m.14709T>C mutation in the tRNA(Glu) gene could be a cause of mitochondrial
      diabetes in Tunisian affected families. In addition, the heteroplasmic loads
      correlated with the severity and the onset of mitochondrial diabetes in one
      family but not in the other, suggesting the presence of environmental factors or
      nuclear modifier genes.

PMID- 20045354
TI  - Epileptogenic temporal cavernous malformations: operative strategies and
      postoperative seizure outcomes.
AB  - Operative treatment of epileptogenic cavernous malformations (CM) continues under
      debate. Most studies focus on surgery for supratentorial CM in general. For
      temporal lobe CM, surgical decision-making concerns in particular whether to
      perform lesionectomy alone or the additional excision of mesial temporal
      structures. The purpose of this case series was to evaluate operative strategies
      used to treat epileptogenic temporal CM and to report resultant postoperative
      seizure outcomes. Twelve consecutive cases of patients with medically intractable
      epilepsy who underwent operation for temporal CM between 1996 and 2006 were
      retrospectively reviewed. When the temporal CM directly invaded the hippocampus
      or amygdala, the affected structures were resected in addition to the lesion;
      when the CM was located in the superficial temporal cortex, and there was no
      radiographic evidence of hippocampal sclerosis, lesionectomy alone was done; with
      CM located between the superficial temporal cortex and the mesial temporal
      region, other factors were considered in decision-making, such as lesion
      proximity to the deep mesiotemporal structures and preoperative epilepsy
      duration. For six of the twelve patients, extended lesionectomy (EL) alone was
      done; for the other six, tailored anteromedial temporal resection with
      hippocampectomy and/or amygdalectomy was performed in addition to EL.
      Postoperatively, 11 patients - all with preoperative VEM demonstrating
      electroclinical seizure patterns concordant with lesion location - were seizure
      free. We conclude that epileptogenic temporal CM are surgically remediable, when
      approached with the above operative strategies and presurgical VEM. On the basis
      of these postoperative seizure control results, we recommend consideration of
      concurrent resection of mesial temporal structures with EL for certain temporal
      CM.

PMID- 20045355
TI  - Thymoproteasome shapes immunocompetent repertoire of CD8+ T cells.
AB  - How self-peptides displayed in the thymus contribute to the development of
      immunocompetent and self-protective T cells is largely unknown. In contrast, the
      role of thymic self-peptides in eliminating self-reactive T cells and thereby
      preventing autoimmunity is well established. A type of proteasome, termed
      thymoproteasome, is specifically expressed by thymic cortical epithelial cells
      (cTECs) and is required for the generation of optimal cellularity of CD8+ T
      cells. Here, we show that cTECs displayed thymoproteasome-specific peptide-MHC
      class I complexes essential for the positive selection of major and diverse
      repertoire of MHC class I-restricted T cells. CD8+ T cells generated in the
      absence of thymoproteasomes displayed a markedly altered T cell receptor
      repertoire that was defective in both allogeneic and antiviral responses. These
      results demonstrate that thymoproteasome-dependent self-peptide production is
      required for the development of an immunocompetent repertoire of CD8+ T cells.

PMID- 20045356
TI  - Vivo-Morpholino knockdown of alphaIIb: A novel approach to inhibit thrombocyte
      function in adult zebrafish.
AB  - Knockdown of protein function by antisense oligonucleotides has been used to
      understand the protein function not only in development but also in human
      diseases. Recently, Vivo-Morpholinos, chemically modified morpholinos which
      penetrate the cells, have been used in adult experimental animal models to alter
      the splicing and thereby change the protein expression. Until now, there have
      been no such studies using Vivo-Morpholinos to evaluate hemostatic function in
      adult animals. We injected alphaIIb Vivo-Morpholinos intravenously into adult
      zebrafish. Thrombocyte function was assayed by time to aggregation assay of the
      citrated blood, annexin V binding to thrombocytes, and gill bleeding. The
      thrombocyte functional inhibition occurred in 24 h after alphaIIb Vivo
      Morpholinos injection and reached a maximum in 48 h. However, in 72 h, the
      inhibition was no longer observed. Reduction of annexin V binding to thrombocytes
      and increased gill bleeding were observed 48 h after alphaIIb Vivo-Morpholino
      injections. The action of the alphaIIb Vivo-Morpholino was demonstrated by the
      presence of an alternatively spliced alphaIIb mRNA and the reduction of alphaIIb
      in thrombocytes of fish treated with alphaIIb Vivo-Morpholino. These results
      provide the first proof of principle that thrombocyte function can be inhibited
      by thrombocyte-specific Vivo-Morpholinos in adult zebrafish and presents an
      approach to knockdown thrombocyte-specific genes to conduct biochemical studies
      in thrombocytes. This study also provides the first antisense antithrombotic
      approach to inhibit thrombocyte function in adult zebrafish.

PMID- 20045357
TI  - Effects of isoflurane upon minimum alveolar concentration and cerebral cortex
      depression in pigs and goats: an interspecies comparison.
AB  - This study compared the effects of isoflurane in pigs (n=10 Yorkshire-Landrace
      cross) and dairy goats (n=10) by evaluation of electroencephalographic (EEG)
      burst suppression thresholds (BST) in the cerebral cortex and minimum alveolar
      concentration (MAC) values in the spinal cord. The study also investigated
      whether individual MAC values can predict the effects of isoflurane on the
      cerebral cortex. MAC values and BST/MAC ratios were significantly different
      between species. Inhibition of movement by isoflurane may be less effective in
      pigs than in goats. No significant correlation was found between individual MAC
      and BST values, indicating that in single animals the individual MAC poorly
      reflects the cerebrocortical depressant effect of isoflurane in pigs and goats.

PMID- 20045358
TI  - Serum concentrations of buprenorphine after oral and parenteral administration in
      male mice.
AB  - Buprenorphine is the most commonly used drug for peri-operative pain relief in
      laboratory rodents. The systemic concentrations of buprenorphine were measured in
      mice following administration intravenously (i.v.), subcutaneously (s.c.), orally
      by gavage and by voluntary ingestion, to determine the post-administration serum
      concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in
      long-lasting high serum concentrations, as did oral gavage administration (24 h
      serum concentration: 110 ng h/mL for both routes of administration). In contrast,
      buprenorphine administered parenterally remained in the circulation for a
      substantially shorter time (24 h serum concentration for i.v. and s.c. were 40 ng
      h/mL and 30 ng h/mL, respectively). This marked difference was probably due to
      the higher dose used for oral administration, which is regarded necessary for
      sufficient analgesic effect, and to the slower absorption of the oral boli, as
      well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary
      ingestion of buprenorphine was found to constitute a practical way to provide
      laboratory mice with efficient pain relief.

PMID- 20045359
TI  - Climate change and the epidemiology of tick-borne diseases of cattle in Africa.

PMID- 20045360
TI  - Acupuncture analgesia for temporal summation of experimental pain: a randomised
      controlled study.
AB  - BACKGROUND: Temporal summation of pain, a phenomenon of the central nervous
      system (CNS), represents enhanced painful sensation or reduced pain threshold
      upon repeated stimulation. This pain model has been used to evaluate the
      analgesic effect of various medications on the CNS. AIMS: The present study aimed
      to evaluate the effects and characteristics of analgesia induced by
      electroacupuncture (EA), manual acupuncture (MA) and non-invasive sham
      acupuncture (SA) in healthy humans on temporal summation of pain. METHODS:
      Thirsty-six pain-free volunteers were randomised into one of the three groups EA
      (2/100 Hz), MA or SA. Acupuncture intervention was on ST36 and ST40 on the
      dominant leg delivered by an acupuncturist blinded to the outcome assessment.
      Both subjects and the evaluator were blinded to the treatment allocation. Pain
      thresholds to a single pulse (single pain threshold, SPT) and repeated pulses
      electrical stimulation (temporal summation thresholds, TST) were measured before,
      30 min after and 24h after each treatment. RESULTS: The baseline values of three
      groups were comparable. Compared to SA, EA significantly increased both SPT and
      TST immediately after the treatment on the treatment leg as well as 24h after on
      both the treatment and non-treatment legs (ANOVA, p<0.05). MA also increased SPT
      and TST, but the changes were not significantly different from those induced by
      SA. CONCLUSION: EA induces bilateral, segmentally distributed and prolong
      analgesia on both SPT and TST, indicating a non-centrally specific effect. This
      effect needs to be verified with heat or mechanical model and in pain patients.

PMID- 20045361
TI  - Efficient heteronuclear dipolar decoupling in solid-state nuclear magnetic
      resonance at rotary resonance conditions.
AB  - We introduce here a heteronuclear dipolar decoupling scheme in solid-state
      nuclear magnetic resonance that performs efficiently at the rotary resonance
      conditions, where otherwise dipolar couplings are re-introduced. Results are
      shown proving the efficiency of this scheme at two magnetic fields under magic
      angle spinning frequencies of 30 and 20 kHz.

PMID- 20045362
TI  - Transient visual loss and isolated disk edema in juvenile nasopharyngeal
      angiofibroma.
AB  - Juvenile nasopharyngeal angiofibroma is a well-described but rare benign tumor
      that mainly affects adolescent boys. Although it is capable of extravagant local
      extension and tissue destruction, the tumor is amenable to effective therapy.
      Ocular or visual complications have been little noted in the literature. We
      report a case whose sole symptom was unilateral transient visual impairment and
      findings were limited to a nonspecific optic disk edema.

PMID- 20045363
TI  - The role of visually evoked potentials in the management of hemispheric arachnoid
      cyst compressing the posterior visual pathways.
AB  - We report a case of an occipital arachnoid cyst in an infant, managed on the
      basis of changes in visually evoked potentials (VEPs). A significant asymmetry of
      VEP responses prompted neurosurgical intervention, which improved visual behavior
      and electrical response to both pattern and flash stimuli.

PMID- 20045364
TI  - Unilateral megalopapilla and contralateral optic nerve hypoplasia: a case report
      and review of the literature.
AB  - We report the incidental finding of megalopapilla in the contralateral eye of a
      10-year-old black child with optic nerve hypoplasia. Megalopapilla is a rare
      entity characterized by an enlarged optic disk without other morphologic
      abnormalities except for an enlarged cup/disk ratio. To the best of our
      knowledge, the concurrence of megalopapilla and optic nerve hypoplasia in the
      same individual has not been reported previously.

PMID- 20045365
TI  - Acute proptosis in a newborn infant: a presentation of infantile dural fistula.
AB  - Rapidly increasing proptosis is rare in a newborn. The causes are diverse, and
      determining an exact etiology is difficult. We report a case of acute proptosis
      in a 26 day old infant due to dural fistula. To our knowledge, this is the
      youngest reported patient with a dural fistula. A multidisciplinary approach was
      essential to understanding the etiology of the proptosis in this child and
      providing adequate and successful treatment.

PMID- 20045366
TI  - Miglustat in adult and juvenile patients with Niemann-Pick disease type C: long
      term data from a clinical trial.
AB  - A randomized, controlled trial of miglustat indicated that miglustat (Zavesca)
      stabilized neurological disease over 12 months in adult and juvenile patients
      with Niemann-Pick disease type C (NP-C). We report data from a non-controlled,
      open-label extension to this initial randomized trial. All patients completing
      the randomized trial were allowed to continue treatment in a 12-month, non
      controlled open-label extension. Those completing 12 months of extension therapy
      could continue further on miglustat in a 'continued extension' phase. From a
      total of 29 patients in the randomized phase (mean [+/-SD] age 24.6+/-9.1 ears;
      52% female), 21 completed 12 months of therapy with miglustat (17 of whom
      received miglustat in the initial randomized phase, and four in the extension
      phase), and 15 patients (all from the miglustat-randomized group) completed 24
      months on miglustat. Mean horizontal saccadic eye movement velocity (HSEM-alpha)
      indicated improvement in the 12-month miglustat group, and stabilization in the
      24-month group; swallowing was improved or stable in 86% and in up to 93%,
      respectively. Ambulation was stabilized in both the 12- and 24-month groups. In
      an exploratory disease stability analysis of prospective data on key parameters
      of disease progression (HSEM-alpha, swallowing, ambulation and cognition), 13/19
      (68%) patients receiving >or= 12 months' miglustat therapy had stable disease.
      Among all patients receiving >or= 1 dose of miglustat (n=28), the most frequent
      adverse events were diarrhoea, weight decrease, flatulence and tremor. Overall,
      these data suggest that long-term miglustat therapy stabilizes neurological
      disease and is well tolerated in adult and juvenile patients with NP-C.

PMID- 20045367
TI  - Evaluation of susceptibility testing methods for polymyxin.
AB  - BACKGROUND: The widespread resistance in Gram-negative bacteria has necessitated
      evaluation of the use of older antimicrobials such as polymyxins. In the present
      study we evaluated the different susceptibility testing methods for polymyxins B
      and E against Gram-negative bacteria using the new Clinical and Laboratory
      Standards Institute (CLSI) guidelines. METHODS: The susceptibility of 281
      multidrug-resistant (MDR) Gram-negative bacteria (GNB) to polymyxin B was
      evaluated, comparing broth microdilution (BMD; reference method), agar dilution,
      E-test, and disk diffusion. Disk diffusion testing of polymyxin B was also
      performed against 723 MDR GNB. RESULTS: Twenty-four of 281 (8.5%) isolates were
      found to be resistant to polymyxin B by the reference BMD method. The rates of
      very major errors for agar dilution and E-test (for polymyxin B) were 0.7% and
      1%, respectively, and those for disk diffusion (for polymyxin B and polymyxin E)
      were 1% and 0.7%, respectively. For the 257 isolates found sensitive by reference
      BMD, the rates of major errors by agar dilution and E-test (for polymyxin B) were
      2.4% and 0%, respectively, and those for disk diffusion (polymyxin B and
      polymyxin E) were 0% and 0.7%, respectively. Twenty-six (3.6%) of the 723 Gram
      negative isolates were resistant to polymyxin B by disk diffusion. CONCLUSION:
      The E-test and agar dilution methods showed good concordance with BMD. The disk
      diffusion method can be useful for initial screening in diagnostic laboratories.

PMID- 20045368
TI  - The importance of skin biopsy in the diverse clinical manifestations of
      disseminated candidiasis.

PMID- 20045369
TI  - Gonococcal septic shock, acute respiratory distress syndrome, and multisystem
      organ failure: a case report.
AB  - We describe the first reported case of gonococcal septic shock with associated
      acute respiratory distress syndrome and multisystem organ failure, in which the
      patient made a full recovery, and add to the paucity of descriptive literature on
      gonococcal sepsis. The case was a 36-year-old previously healthy Aboriginal
      female from northern Canada. Treatment included fluid resuscitation, vasoactive
      drugs, mechanical ventilation, antimicrobial therapy, corticosteroid replacement,
      activated protein C, and general supportive care. In addition to being the first
      reported case of gonococcal septic shock with associated acute respiratory
      distress syndrome and multisystem organ failure in which the patient made a full
      clinical recovery this is also the first case of gonococcal septic shock treated
      with activated protein C; an association between its use and the favorable
      outcome is postulated, but cannot be confirmed.

PMID- 20045370
TI  - Activities of cyclooxygenases, and levels of prostaglandins E2 and F2alpha, in
      fetopathy associated with experimental diabetic gestation.
AB  - AIM: The present study investigated the cyclooxygenase (COX) pathway to elucidate
      any changes that may be involved in the mechanism(s) underlying diabetic
      fetopathy. METHODS: Diabetes was induced in female rats (n=12) by two successive
      daily injections of 55 mg/kg streptozotocin, while control animals (n=10) were
      injected with a buffer solution; hyperglycaemia was confirmed by blood glucose
      levels greater than 11 mmol/L. The study female rats were made pregnant and, on
      day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and
      membranes dissected out of the uterine horns. Following morphological
      examination, the fetuses, placentas and membranes were homogenized, and used to
      measure COX activities and prostaglandin (PG) E(2) and PGF(2alpha) levels.
      RESULTS: Fetuses from diabetic mothers exhibited significantly (P<0.05) shorter
      crown-to-rump lengths, lower body weights and heavier placental weights. The
      activity of COX-1 in the fetuses, placentas and membranes from diabetic mothers
      represented a small percentage of total COX activity compared with that of COX-2.
      The presence of a COX-1 inhibitor in the control and diabetic rats was
      investigated and found to be negative. The activity of COX-2 in malformed fetuses
      from diabetic mothers was significantly lower (P<0.05) compared with non
      malformed fetuses from control and diabetic mothers. The mean level of PGE(2) in
      fetuses from diabetic mothers was significantly (P<0.05) lower than that in
      controls. In contrast, the biggest increases in PGF(2alpha) were observed in the
      malformed diabetic fetuses, placentas and membranes. CONCLUSION: The increased
      production of PGF(2alpha) probably proceeds, at least in part, independently of
      the COX pathway and via the isoprostane route. However, it is unclear whether the
      relatively high levels of PGF(2alpha) are causally related to, or simply
      coincidental with, fetal malformation.

PMID- 20045371
TI  - Anti-IL-1 molecules: new comers and new indications.
AB  - The interleukin 1 family is composed by the interleukin 1 (IL-1) and its natural
      occurring inhibitor, the interleukin 1 receptor antagonist (IL-1Ra). The role of
      both molecules in rheumatoid arthritis has been widely established, and in this
      sense new molecules blocking IL-1 actions are under investigation. Anakinra is
      the recombinant form of IL-1Ra, and has proven to be well tolerated and indicated
      in the treatment of rheumatoid arthritis. Nevertheless, other molecules such as
      mAb anti-IL-1 and IL-1 Trap are being developed. Moreover, the recent relation of
      IL-1 in the inflammasome and pathways of innate immunity has lead to new
      indications of anti-IL-1 molecules, especially in the autoinflammatory syndromes
      as well as in other inflammatory diseases. Herein we have performed a review of
      the literature, limited to English language journals (PUBMED search: combination
      of descriptors IL-1 and anakinra, systemic juvenile idiopathic arthritis, adult's
      onset Still's disease, autoinflammatory syndromes, gout, pseudogout, ankylosing
      spondylitis, and systemic lupus erythematosus from January 1985-December 2008)
      emphasizing the possible new indications. Although sufficient data is not yet
      available to fully assess the efficacy and safety of anti-IL-1 molecules in
      patients with inflammatory disorders other than rheumatoid arthritis, new data is
      promising.

PMID- 20045372
TI  - Putting pregnancy in its place: conceiving pregnancy as carework in the
      workplace.
AB  - This paper contributes to understandings of the relationship between pregnancy,
      health and place by exploring how health advice on pregnancy may be implemented,
      in practice, 'at work'. The paper first defines the following of health advice on
      pregnancy as a form of informal 'carework' which obliges pregnant women to
      implement caring practices comprising emotional and embodied labour. It then
      observes how health advice on pregnancy carework pays little regard to the impact
      of place. Drawing upon in-depth interviews with 15 professionally employed
      mothers/expectant mothers; the paper suggests that the performance of pregnancy
      carework may be incompatible with workplace settings. The tensions are
      highlighted between medical representations of pregnancy as a 'condition' and the
      treatment of pregnancy, within professional workplaces, as 'not an illness'. The
      question is raised as to whether insufficient reference to place within health
      advice reflects underlying gendered expectations that pregnancy carework ought to
      be performed within the home.

PMID- 20045373
TI  - Non-mammalian animal models to study infectious disease: worms or fly fishing?
AB  - A major challenge in studying human infectious diseases is to understand in
      detail the molecular bases, including both pathogen and host-related factors,
      which contribute to disease development. Non-mammalian models have proven to be
      of great value for our understanding of disease and have shown conservation in
      fundamental virulence mechanisms for the infection of evolutionary divergent
      hosts. In this review we describe recent advances with three major non-mammalian
      models used for analysis of infectious disease in humans; the nematode
      Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish
      Danio rerio.

PMID- 20045374
TI  - A new biomarker of protein oxidation degree and site using angiotensin as the
      target by MS.
AB  - Hydroxyl radicals generated from Fenton reaction were used to damage the
      angiotensin. The oxidative damage degree and sites of peptides were measured by
      HPLC-MS and MS/MS. Experimental results proved that the oxidative damage degree
      increased with longer reaction time. The results also showed that the side chains
      of phenylalanine and tyrosine in angiotension can be attacked by hydroxyl
      radicals to form the oxidative products. A new strategy was established to
      monitor the oxidative degree and sites of peptides and laid the foundation for
      protein oxidation. This method can be used to investigate the mechanism of
      protein oxidative damage caused by oxidative stress which is induced by
      environmental pollutants and physiological activities. There will also be a wide
      application in the research of pathogenesis of some disease related to oxidative
      stress.

PMID- 20045375
TI  - State dependent properties of epileptic brain networks: comparative graph
      theoretical analyses of simultaneously recorded EEG and MEG.
AB  - OBJECTIVE: To investigate whether functional brain networks of epilepsy patients
      treated with antiepileptic medication differ from networks of healthy controls
      even during the seizure-free interval. METHODS: We applied different rules to
      construct binary and weighted networks from EEG and MEG data recorded under a
      resting-state eyes-open and eyes-closed condition from 21 epilepsy patients and
      23 healthy controls. The average shortest path length and the clustering
      coefficient served as global statistical network characteristics. RESULTS:
      Independent on the behavioral condition, epileptic brains exhibited a more
      regular functional network structure. Similarly, the eyes-closed condition was
      characterized by a more regular functional network structure in both groups. The
      amount of network reorganization due to behavioral state changes was similar in
      both groups. Consistent findings could be achieved for networks derived from EEG
      but hardly from MEG recordings, and network construction rules had a rather
      strong impact on our findings. CONCLUSIONS: Despite the locality of the
      investigated processes epileptic brain networks differ in their global
      characteristics from non-epileptic brain networks. Further methodological
      developments are necessary to improve the characterization of disturbed and
      normal functional networks. SIGNIFICANCE: An increased regularity and a
      diminished modulation capability appear characteristic of epileptic brain
      networks.

PMID- 20045376
TI  - The effect of contraction intensity on force fluctuations and motor unit
      entrainment in individuals with essential tremor.
AB  - OBJECTIVES: Quantify the effect of increasing contraction intensity on the
      amplitude of force fluctuations and neuromuscular and force tremor spectral
      power. METHODS: Twenty-one subjects with essential tremor (ET) and 22 healthy
      controls applied isometric wrist extension contractions. Various sub-maximal
      contraction intensities were evaluated (5%-, 10%-, 20%- and 30%-MVC). Force
      fluctuations and wrist extensor neuromuscular activity were recorded using a load
      cell and electromyography (EMG). RESULTS: Higher contraction intensities were
      associated with larger amplitude force fluctuations and greater neuromuscular
      activation. However, spectral power associated with tremor peaks remained
      relatively constant (EMG) or decreased (force) with increasing contraction
      intensity. CONCLUSIONS: Motor unit entrainment associated with centrally
      generated oscillatory inputs does not increase with greater levels of muscle
      activation. SIGNIFICANCE: Rather than influencing a constant proportion of active
      motor units, abnormal oscillatory drive influences a relative constant number of
      total motor units. When combined with the findings from our previous study on
      postural tremor, the present results provide preliminary evidence that abnormal
      stretch reflex activity may contribute to this motor unit entrainment.

PMID- 20045377
TI  - Depressive disorders may more commonly be related to circadian phase delays
      rather than advances: time will tell.

PMID- 20045378
TI  - Guidelines for the management of antiplatelet therapy in patients with coronary
      stents undergoing non-cardiac surgery.

PMID- 20045379
TI  - Targeting the redox regulation of SERCA in vascular physiology and disease.
AB  - The sarco/endoplasmic reticulum calcium ATPase (SERCA) is essential for the
      control of intracellular free Ca(2+) levels. Although the importance for this
      enzyme in cardiac myocytes is well recognized, it is only recently that SERCA has
      been identified as an important effector of nitric oxide (NO) action in vascular
      cells. NO can stimulate the uptake of cytosolic Ca(2+) via SERCA by adducting
      glutathione to the reactive cysteine-674. Mutation of this single amino acid
      prevents the stimulation of Ca(2+) uptake by NO, as well as its ability to
      inhibit smooth muscle cell functions including migration. NO function is impaired
      in a variety of cardiovascular diseases, including diabetes,
      hypercholesterolemia, and atherosclerosis, which are all associated with SERCA
      dysfunction caused by the increased oxidants in these diseases. Targeting the
      oxidant sources in vascular diseases to prevent SERCA from being oxidized and/or
      increasing the expression of SERCA may improve vascular disease development.

PMID- 20045381
TI  - Endoplasmic reticulum stress as a progression factor for kidney injury.
AB  - Dysfunction of endoplasmic reticulum (ER) maintaining protein homeostasis can
      result from various disturbances, including hypoxia or oxidative stress, which
      lead to an imbalance between protein-folding capacity and protein-folding load.
      This in turn leads to ER stress and induction of the unfolded protein response
      (UPR). The UPR initially serves as an adaptive response, but also induces
      apoptosis in cells under severe or prolonged ER stress. Accumulating evidence
      indicates that ER stress contributes to glomerular and tubular damages in kidney
      disease. These findings emphasize the importance of ER stress as a new
      progression factor and the interesting future possibility of renoprotective
      strategies targeting ER stress. These therapeutic approaches may act by breaking
      the vicious cycle of oxidative stress, hypoxia, and ER stress.

PMID- 20045380
TI  - Extracellular matrix molecules: endogenous danger signals as new drug targets in
      kidney diseases.
AB  - Extracellular matrix (ECM) components, commonly thought to function purely as
      structural elements are now demonstrated to act as signaling molecules. With the
      identification of matrix-derived endogenous ligands of Toll-like and NOD-like
      receptors of innate immunity, a general question about the mechanisms of soluble
      ECM components signaling as autonomous triggers of sterile or enhancers of
      pathogen-mediated inflammation gained notable relevance. They act as fundamental
      danger signals signifying tissue injury by eliciting a robust proinflammatory
      response. Immense therapeutic potential resides in translating this knowledge
      into the development of Toll-like and NOD-like receptor inhibitors. This review
      focuses on the role of ECM-derived ligands of innate immunity receptors as
      mediators of renal inflammation and promising pharmacological targets in kidney
      disease.

PMID- 20045382
TI  - Strengthening and updating supervising staff nurses in educational workshops--an
      international partnership project.
AB  - As part of a collaborative project involving Tanzania and Sweden, workshops were
      arranged for staff nurses in order to develop a forum for discussing the raised
      demands for supervision of nursing students during their clinical education. The
      aim was to meet nurses in educational workshops to initiate a dialogue on their
      views and experiences of supporting and supervising nursing students in their
      clinical studies. Their experiences of the workshops were also requested. Two
      groups of nurses in Tanzania (n=30), and six groups in Sweden (n=60)
      participated. The content, which was agreed between the project leaders in
      Tanzania and Sweden was carried out either on a whole day workshops or divided at
      three different occasions. Questionnaires were given before and about two months
      after, and workshops were also evaluated with an open-ended question immediately
      after. The nurses both in Tanzania and in Sweden appreciated the workshops as a
      possibility to create a dialogue and to discuss challenges in the supervision of
      students. Their views and experiences of the supervision role showed awareness of
      staff nurses as role models and teachers. Accomplishment of this partnership co
      operation through arranging workshops has shown to be an easy and simple way of
      giving support to staff nurses for the supervision task.

PMID- 20045383
TI  - Levetiracetam as add-on therapy in different subgroups of "benign" idiopathic
      focal epilepsies in childhood.
AB  - Several recent studies have shown that levetiracetam (LEV) can be beneficial in
      the treatment of children with typical rolandic epilepsy (RE). Reports about the
      effectiveness of LEV in the treatment of children with the less benign variants
      in the spectrum of "benign" idiopathic focal epilepsies are still rare. Little is
      known about the effect of LEV on interictal epileptiform discharges in these
      syndromes. We report on LEV therapy in 32 children (mean age: 10.6 years, range:
      4-14) with RE or variants like atypical benign idiopathic partial epilepsy of
      childhood (ABIPEC), Landau-Kleffner syndrome (LKS), and continuous spikes and
      waves during sleep (CSWS) and in children with benign idiopathic focal
      epileptiform discharges of childhood (BIFEDC). Cognitive and behavioral problems,
      not seizures, may be related to the pathological EEG. Patients with a reduction
      in seizure frequency >50% and/or reduction in BIFEDC >90% 3 months after having
      started LEV therapy were defined as responders. The average dose of LEV was 39
      mg/kg body wt per day; LEV was given in monotherapy to 31.3% of the patients.
      Overall, 20 of 32 patients (62.5%) did benefit: 12 of 24 patients had a >50%
      reduction in seizure frequency; 2 of 24 patients (8.3%) were completely seizure
      free; 18 of 32 patients (56.3%) had a >90% reduction in BIFEDC (including CSWS);
      6 of 32 (18.8%) had an EEG completely free of epileptiform discharges; and 17 of
      32 (53.1%) showed improvement in cognition and/or language functions and/or
      behavior. Surprisingly, LEV tended to be more helpful in atypical rolandic
      epilepsies and other variants.

PMID- 20045384
TI  - Prevalence and risk factors for recovery of filamentous fungi in individuals with
      cystic fibrosis.
AB  - BACKGROUND: Filamentous fungi are frequently recovered from respiratory cultures
      of individuals with CF. METHODS: A CF cohort database was utilized to determine
      filamentous fungal prevalence and risk factors. RESULTS: The prevalence of
      filamentous fungal isolation increased from 2.0% in 1997 to 28.7% in 2007. The
      odds of isolating filamentous fungi during a quarter was greater in CF adults
      [p<0.001], during chronic oral antibiotic use [p=0.002] and increased with each
      10% drop in FEV(1) percent predicted [p=0.005], while inhaled corticosteroids
      surprisingly decreased the likelihood [p=0.012]. The direction of these effects
      persisted after excluding individuals with ABPA. A sub-analysis determined older
      age [p=0.019] and use of inhaled antibiotics [p=0.011] were independent risk
      factors for onset of fungal colonization. CONCLUSIONS: This study suggests that
      isolation of filamentous fungi in CF at JHH has increased and risk factors
      include older age, decreased lung function, and chronic oral antibiotics.

PMID- 20045385
TI  - Validation and application of a liquid chromatography-tandem mass spectrometric
      method for quantification of the drug transport probe fexofenadine in human
      plasma using 96-well filter plates.
AB  - A rapid method to determine fexofenadine concentrations in human plasma using
      protein precipitation in 96-well plates and liquid chromatography-tandem mass
      spectrometry was validated. Plasma proteins were precipitated with acetonitrile
      containing the internal standard fexofenadine-d6, mixed briefly, and then
      filtered into a collection plate. The resulting filtrate was diluted and injected
      onto a Phenomenex Gemini C18 (50 mm x 2.0 mm, 5 microm) analytical column. The
      mobile phase consisted of 0.1% formic acid, 5 mM ammonium acetate in deionized
      water and methanol (35:65, v/v). The flow rate was 0.2 ml/min and the total run
      time was 2 min. Detection of the analytes was achieved using positive ion
      electrospray ionization and high resolution multiple reaction monitoring mode (H
      SRM). The linear standard curve ranged from 1 to 500 ng/ml and the precision and
      accuracy (intra- and inter-run) were within 4.3% and 8.0%, respectively. The
      method has been applied successfully to determine fexofenadine concentrations in
      human plasma samples obtained from subjects administered a single oral dose of
      fexofenadine. The method is rapid, sensitive, selective and directly applicable
      to human pharmacokinetic studies involving fexofenadine.

PMID- 20045386
TI  - Quantification of theobromine and caffeine in saliva, plasma and urine via liquid
      chromatography-tandem mass spectrometry: a single analytical protocol applicable
      to cocoa intervention studies.
AB  - Targeted analyses of clinically relevant metabolites in human biofluids often
      require extensive sample preparation (e.g., desalting, protein removal and/or
      preconcentration) prior to quantitation. In this report, a single ultra
      centrifugation based sample pretreatment combined with a designed liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) protocol provides selective
      quantification of 3,7-dimethylxanthine (theobromine) and 1,3,7-trimethylxanthine
      (caffeine) in human saliva, plasma and urine samples. The optimized
      chromatography permitted elution of both analytes within 1.3 min of the applied
      gradient. Positive-mode electrospray ionization and a triple quadruple MS/MS
      instrument operated in multiple reaction mode were used for detection. (13)C(3)
      isotopically labeled caffeine was included as an internal standard to improve
      accuracy and precision. Implementing a 20-fold dilution of the isolated low MW
      biofluid fraction prior to injection effectively minimized the deleterious
      contributions of all three matrices to quantitation. The assay was linear over a
      160-fold concentration range from 2.5 to 400 micromol L(-1) for both theobromine
      (average R(2) 0.9968) and caffeine (average R(2) 0.9997) respectively. Analyte
      peak area variations for 2.5 micromol L(-1) caffeine and theobromine in saliva,
      plasma and urine ranged from 5 and 10% (intra-day, N=10) to 9 and 13% (inter-day,
      N=25) respectively. The intra- and inter-day precision of theobromine and
      caffeine elution times were 3 and <1% for all biofluids and concentrations
      tested. Recoveries for caffeine and theobromine ranged from 114 to 118% and 99 to
      105% at concentration levels of 10 and 300 micromol L(-1). This validated
      protocol also permitted the relative saliva, plasma and urine distribution of
      both theobromine and caffeine to be quantified following a cocoa intervention.

PMID- 20045387
TI  - Application of the Goes double-skin peri-areolar mastopexy with and without
      implants: A 14-year experience.
AB  - Peri-areolar mastopexy is commonly used for mild ptosis requiring no more than
      3cm of nipple elevation. The nature of areolar scar and gland remodelling
      inherent to a circular skin reduction prompts circumspection when correcting more
      moderate-to-severe cases. The purpose herein is to convey the reproducibility and
      applicability of the Goes double-skin peri-areolar mastopexy without mesh, for
      breast ptosis requiring nipple elevation of 4-9cm, in a series outside the work
      of the principal innovator. A series of 217 consecutive patients underwent
      circumareolar eccentric skin excision based on four cardinal landmarks,
      deepithelialised dermal sleeve and glandular reshaping with and without implants
      (174 augmentation-mastopexies and 43 mastopexies). Implantation and implant
      change involved the use of saline implants placed in the subpectoral space.
      Average nipple elevation was 5.1cm in the augmentation-mastopexy group and 6.5cm
      in the mastopexy group. There were major complications in 4.4% of breasts and
      occurred only in the mastopexy-augmentation group. There was no nipple loss,
      serious infection or haematoma. There were minor complications in 13.1% of
      breasts (11.8% in the mastopexy-augmentation group, and 18.6% in the mastopexy
      group). A minimal (10%) areolar necrosis occurred on a breast in one patient
      undergoing augmentation-mastopexy for tubular breasts with micromastia. Revision
      rate was 4% for the entire series. Based on the principles of circular skin
      design with fixed skin landmarks, internal breast shaping and special attention
      when augmentation is done simultaneously, the peri-areolar double-skin mastopexy
      can be safe, effective and reproducible when applied to cases of increasing
      complexity.

PMID- 20045389
TI  - Analysis of causes for formation of chimeras.
AB  - The present study investigated cDNA chimeras using two closely related members of
      the rice secretory protein gene family as an example. The chimeras detected in
      initial cDNA products that were amplified using LA Taq polymerase involved two
      categories: single-site type and multiple-site type with the frequency being
      about 20% and 3%, respectively. Further investigation revealed that PCR buffer
      additives and type of DNA polymerase had a major effect on the formation of
      chimeras in mixed-template amplification. Heteroduplex repair by microbial DNA
      repair systems in cDNA cloning was confirmed to produce the chimeras too, but it
      was not the major source.

PMID- 20045390
TI  - Rice endosperm-specific plastidial alpha-glucan phosphorylase is important for
      synthesis of short-chain malto-oligosaccharides.
AB  - Previous genetic studies have indicated that the type L alpha-glucan
      phosphorylase (Pho1) has an essential role during the initiation process of
      starch biosynthesis during rice seed development. To gain insight into its role
      in starch metabolism, we characterized the enzymatic properties of the Pho1
      recombinant form. Pho1 has significantly higher catalytic efficiency toward both
      linear and branched alpha-glucans in the synthesis direction than in the
      degradation direction with equilibrium constants for the various substrates
      ranging from 13 to 45. Pho1 activity is strongly inhibited by its own reaction
      product (Pi) in the synthesis reaction (K(i)=0.69 mM) when amylopectin is the
      primer substrate, but this inhibition is less pronounced (K(i)=14.2 mM) when
      short alpha-glucan chains are used as primers. Interestingly, even in the
      presence of Pi alone, Pho1 not only degrades maltohexaose but also extends them
      to synthesize longer MOSs. Production of a broad spectrum of MOSs (G4-G19) was
      stimulated by both Pi and Glc1P in an additive fashion. Thus, even under
      physiological conditions of high Pi/Glc1P, Pho1 extends the chain length of short
      MOSs which can then be used as subsequent primer by starch synthase activities.
      As ADP-glucose strongly inhibits Pho1 activity, Pho1 likely operates only during
      the initial stage and not during maturation phase of starch synthesis.

PMID- 20045391
TI  - Binding of human angiogenin inhibits actin polymerization.
AB  - Angiogenin is a potent inducer of angiogenesis, a process of blood vessel
      formation. It interacts with endothelial and other cells and elicits a wide range
      of cellular responses including migration, proliferation, and tube formation. One
      important target of angiogenin is endothelial cell-surface actin and their
      interaction might be one of essential steps in angiogenin-induced
      neovascularization. Based on earlier indications that angiogenin promotes actin
      polymerization, we studied the binding interactions between angiogenin and actin
      in a wide range of conditions. We showed that at subphysiological KCl
      concentrations, angiogenin does not promote, but instead inhibits polymerization
      by sequestering G-actin. At low KCl concentrations angiogenin induces formation
      of unstructured aggregates, which, as shown by NMR, may be caused by angiogenin's
      propensity to form oligomers. Binding of angiogenin to preformed F-actin does not
      cause depolymerization of actin filaments though it causes their stiffening.
      Binding of tropomyosin and angiogenin to F-actin is not competitive at
      concentrations sufficient for saturation of actin filaments. These observations
      suggest that angiogenin may cause changes in the cell cytoskeleton by inhibiting
      polymerization of G-actin and changing the physical properties of F-actin.

PMID- 20045392
TI  - Membrane charge dependent states of the beta-amyloid fragment Abeta (16-35) with
      differently charged micelle aggregates.
AB  - Abeta (16-35) is the hydrophobic central core of beta-amyloid peptide, the main
      component of plaques found in the brain tissue of Alzheimer's disease patients.
      Depending on the conditions present, beta-amyloid peptides undergo a
      conformational transition from random coil or alpha-helical monomers, to highly
      toxic beta-sheet oligomers and aggregate fibrils. The behavior of beta-amyloid
      peptide at plasma membrane level has been extensively investigated, and membrane
      charge has been proved to be a key factor modulating its conformational
      properties. In the present work we probed the conformational behavior of Abeta
      (16-35) in response to negative charge modifications of the micelle surface. CD
      and NMR conformational analyses were performed in negatively charged pure SDS
      micelles and in zwitterionic DPC micelles "doped" with small amounts of SDS. To
      analyze the tendency of Abeta (16-35) to interact with these micellar systems, we
      performed EPR experiments on three spin-labeled analogues of Abeta (16-35),
      bearing the methyl 3-(2,2,5,5-tetramethyl-1-oxypyrrolinyl) methanethiolsulfonate
      spin label at the N-terminus, in the middle of the sequence and at the C
      terminus, respectively. Our conformational data show that, by varying the
      negative charge of the membrane, Abeta (16-35) undergoes a conformational
      transition from a soluble helical-kink-helical structure, to a U-turn shaped
      conformation that resembles protofibril models.

PMID- 20045393
TI  - Nanosized self-emulsifying lipid vesicles of diacylglycerol-PEG lipid conjugates:
      biophysical characterization and inclusion of lipophilic dietary supplements.
AB  - Hydrated diacylglycerol-PEG lipid conjugates, glyceryl dioleate-PEG12 (GDO-PEG12)
      and glyceryl dipalmitate-PEG23 (GDP-PEG23), spontaneously form uni- or
      oligolamellar liposomes in their liquid crystalline phase, in distinct difference
      from the PEGylated phospholipids which form micelles. GDP-PEG23 exhibits peculiar
      hysteretic phase behavior and can arrange into a long-living hexagonal phase at
      ambient and physiological temperatures. Liposomes of GDO-PEG12 and its mixture
      with soy lecithin exchange lipids with the membranes much more actively than
      common lecithin liposomes; such an active lipid exchange might facilitate the
      discharging of the liposome cargo upon uptake and internalization, and can thus
      be important in drug delivery applications. Diacylglycerol-PEG lipid liposome
      formulations can encapsulate up to 20-30wt.% lipophilic dietary supplements such
      as fish oil, coenzyme Q10, and vitamins D and E. The encapsulation is feasible by
      way of dry mixing, avoiding the use of organic solvent.

PMID- 20045394
TI  - Regulation of 11beta-hydroxysteroid dehydrogenase 1 and 2 by IGF-1 in mice.
AB  - Two isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1 and 11beta-HSD2)
      play an important role in regulation of glucocorticoid corticosterone (CORT, the
      active form in rodents) by the interconversion between CORT and 11
      dehydrocorticosterone (11DHC, the biologically inert form). 11beta-HSD1 is an
      NADP+/NADPH-dependent oxidoreductase which is mainly expressed in liver and
      kidney, while 11beta-HSD2 is an NAD+-dependent oxidase which is predominantly
      expressed in kidney. The regulation of 11beta-HSD1 and 11beta-HSD2 mRNA (Hsd11b1
      and Hsd11b2) levels and their activities by IGF-1 was performed in liver, kidney,
      and testis of IGF-1 knockout male mice. Real-time PCR showed that Hsd11b1 in
      liver was decreased while Hsd11b2 mRNA level was decreased in kidney of IGF-1
      null mice. 11beta-HSD1 and 11beta-HSD2 activities fluctuated with the changes of
      their respective Hsd11b1 or Hsd11b2 mRNA levels. In conclusion, IGF-I tissue
      specifically regulates Hsd11b1 and Hsd11b2 expression.

PMID- 20045395
TI  - Serum albumin induces osmotic swelling of rat retinal glial cells.
AB  - Edema in the ischemic neural tissue develops by increased vascular permeability
      associated with extravasation of albumin, and by glial swelling. Here, we show
      that bovine serum albumin acutely administered to slices of the rat retina causes
      swelling of glial somata under hypoosmotic conditions. The effect of albumin was
      dose-dependent, with half-maximal and maximal effects at 10 nM and 1 microM,
      respectively, and was mediated by activation of transforming growth factor-beta
      receptor type II, oxidative stress, and the production of arachidonic acid and
      prostaglandins. Albumin-induced glial swelling was prevented by glutamate and
      purinergic receptor agonists. The data suggest that serum albumin may induce
      glial swelling in the presence of osmotic gradients.

PMID- 20045396
TI  - Three weeks voluntary running wheel exercise increases endoplasmic reticulum
      stress in the brain of mice.
AB  - The unfolded protein response (UPR) is a dynamic cellular mechanism for reducing
      endoplasmic reticulum (ER) stress. ER stress occurs from a variety of causes such
      as nutritional deprivation or over-nutrition, expression of misfolded or mutant
      proteins and increased synthesis of secretory protein. Obesity induced by over
      nutrition has been associated with ER stress. Although exercise has a beneficial
      effect in opposing the development of obesity and neurodegenerative diseases,
      there have been no studies on the effect of exercise on ER stress in the brain
      induced by over-nutrition. We have taken advantage of the substantial individual
      differences in voluntary running activity among inbred C57BL/6 mice to
      investigate the relation between ER stress within regions of the brain and
      voluntary running activity in mice fed on either a low fat or high fat diet while
      maintained individually in cages with running wheels. Mice were divided into
      three groups depending on their voluntary running level and compared with a
      sedentary group. ER stress was assayed by real-time PCR and Western blots of the
      UPR pathway markers Xbp1, PERK, eIF2alpha, Hspa5 and ATF6. Three weeks of HFD had
      little effect on ER stress in the brain of the sedentary group compared to
      animals fed the LFD. Higher voluntary running activity was associated with
      increased ER stress in the hypothalamus, hippocampus and cortex. The responses
      were largest in the hypothalamus. The increase in the UPR response in response to
      exercise did not induce apoptotic signals and may thus contribute to the
      protective effect of exercise in preventing neurodegenerative disease.

PMID- 20045397
TI  - Manganese neurotoxic time course is not influenced by L-deprenyl systemic
      treatment: influence of L-deprenyl in manganese neurotoxic time course.
AB  - Unilateral microinjection of manganese into the rat substantia nigra pars
      compacta (SNpc) leads to the death of nigral neurons and a decrease in dopamine
      (DA) within the ipsilateral striatum. L-deprenyl, an irreversible inhibitor of
      monoamine oxidase B, appears to protect or rescue dopaminergic nigral neurons
      from the toxic effects of 6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenyl-1, 2,
      3, 6-tetrahydropiridine (MPTP). In this study we aimed to investigate whether L
      deprenyl is able to influence the manganese neurotoxic time course. L-deprenyl
      rescue activity was evaluated in discontinuous posology and its protective effect
      was evaluated in a continuous one. Apomorphine-induced rotational behavior and
      striatal tyrosine hydroxylase immunostaining (TH-IS) were evaluated in both
      conditions at 24 h, 72 h and 168 h after intranigral microinjections. Our results
      indicate a failure in L-deprenyl to influence the establishment and time course
      of rotational response to apomorphine. Strikingly, a further decrease in the
      tyrosine hydroxylase immunostaining, at 168 h post microinjection in L-deprenyl
      treated rats was obtained. Our data revealed no correlation between an increasing
      rotational behavior and reduction in TH-IS.

PMID- 20045399
TI  - Gyrification brain abnormalities associated with adolescence and early-adulthood
      cannabis use.
AB  - Although cannabis is the most widely used illicit drug in the world, the long
      term effect of its use in the brain remains controversial. In order to determine
      whether adolescence and early-adulthood cannabis use is associated with gross
      volumetric and gyrification abnormalities in the brain, we set up a cross
      sectional study using structural magnetic resonance imaging in a sample of
      general population subjects. Thirty cannabis-using subjects (mean age, 25.7
      years; mean duration of regular use, 8.4 years, range: 3-21) with no history of
      polydrug use or neurologic/mental disorder and 44 non-using control subjects
      (mean age, 25.8 years) were included. Cannabis users showed bilaterally decreased
      concavity of the sulci and thinner sulci in the right frontal lobe. Among non
      users, age was significantly correlated with decreased gyrification (i.e., less
      concave sulci and more convexe gyri) and decreased cortical thickness, supporting
      the notion of age-related gyrification changes. However, among cannabis users
      gyrification indices did not show significant dependency on age, age of regular
      cannabis use initiation, or cumulative exposure to cannabis. These results
      suggest that cannabis use in adolescence and early-adulthood might involve a
      premature alteration in cortical gyrification similar to what is normally
      observed at a later age, probably through disruption of normal neurodevelopment.

PMID- 20045398
TI  - Amyloid and Tau accumulate in the brains of aged hydrocephalic rats.
AB  - AD pathology is often seen in cortical biopsies of NPH patients. It remains
      unclear whether these findings are coincidental or causally related. In an aged
      animal model of NPH, we quantify Abeta and pTau accumulation and describe its
      temporal and spatial distribution. One-year-old male Sprague-Dawley rats had
      hydrocephalus induced by cisternal kaolin injection. Immunohistochemistry (IMHC)
      for AbetaPP, Abeta40, Abeta42 and pTau (epitope pT231) and ELISA for Abeta40,
      Abeta42 and pT231 were performed on controls and after 2, 6 and 10 weeks of
      hydrocephalus. Rats had double-label fluorescence IMHC for localization of
      Abeta42 and pT231. IMHC showed no change in neuronal AbetaPP expression following
      hydrocephalus. Abeta42 appeared earliest in CSF clearance pathways, p<0.05, and
      also showed significant rises in perivascular spaces and in cortical parenchyma.
      Mean ELISA values for Abeta40 and Abeta42 increased three- to four-fold in
      hydrocephalic rats at 6 and 10 weeks. Abeta40 increased between 2 and 6 weeks
      (p=0.0001), and remained stable at 10 (p=0.0002); whereas Abeta42 was elevated at
      2 weeks (p<0.04) and remained at 6 (p=0.015). PTau at 6 and 10 weeks showed AD
      like increased neuronal somatic staining and loss of dendritic staining. ELISA
      demonstrated increased pT231 in hydrocephalic rats at 10 weeks (p<0.0002). Double
      label fluorescence for Abeta42 and pT231 revealed intraneuronal co-localization.
      Hydrocephalus in the elderly rat, therefore, can induce both Abeta and pTau
      accumulation. As distinct from brain injury models, no increase in AbetaPP
      expression was demonstrated. Rather, altered CSF dynamics appears to impair Abeta
      clearance in this NPH model.

PMID- 20045400
TI  - Effects of anti-CD70 mAb on Theiler's murine encephalomyelitis virus-induced
      demyelinating disease.
AB  - Ligation of CD27, a member of the tumor necrosis factor (TNF) receptor family, by
      its ligand CD70 is thought to be important in T cell activation, expansion and
      survival, B cell activation, and NK cell activation. We examined the role of CD70
      in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV
      IDD) mice. Blocking of CD70 in effector phase by anti-CD70 monoclonal antibody
      (mAb) suppressed the development of TMEV-IDD. The number of IFN-gamma- or TNF
      alpha-producing cells in the spleen and mRNA levels of IFN-gamma and TNF-alpha in
      spinal cord were decreased in mice treated with anti-CD70 mAb at the effector
      phase. In contrast, treatment with anti-CD70 mAb in induction phase failed to
      reduce these responses, compared to nonspecific IgG-treated control mice. These
      data suggest that CD70 is critically involved in the pathogenesis of TMEV-IDD and
      that antibodies against CD70 could be a novel therapeutic approach in the
      clinical treatment of demyelinating diseases such as human multiple sclerosis.

PMID- 20045401
TI  - Synaptic contribution of Ca2+-permeable and Ca2+-impermeable AMPA receptors on
      isolated carp retinal horizontal cells and their modulation by Zn2+.
AB  - Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors are co-expressed on carp
      retinal horizontal cells. In the present study, we examined the synaptic
      contribution and Zn(2+) modulatory effect of these two AMPA receptor subtypes
      using whole-cell patch clamp technique. Specific Ca(2+)-permeable AMPA receptor
      antagonist (1-naphthyl acetyl spermine, NAS) and selective Ca(2+)-impermeable
      AMPA receptor blocker (pentobarbital, PB) were used to separate the glutamate
      response in isolated H1 horizontal cell mediated by these two subtypes of AMPA
      receptors respectively. Application of 100 microM NAS substantially suppressed
      the current elicited by 3 mM glutamate and the remaining NAS-insensitive
      component was completely blocked by application of 100 microM PB. In addition,
      Zn(2+) had dual effects on Ca(2+)-permeable AMPA receptor-mediated current: at
      low concentration (10 microM), Zn(2+) potentiated the current, but at higher
      concentrations (100 and 1000 microM), Zn(2+) reduced the current in a dose
      dependent manner. However, Zn(2+) (10, 100 and 1000 microM) failed to modulate
      the NAS-insensitive current mediated by Ca(2+)-impermeable AMPA receptors.
      Overall, our results suggest that Ca(2+)-permeable AMPA receptors contribute more
      to the cell's glutamate-response than Ca(2+)-impermeable AMPA receptors.
      Furthermore, Zn(2+) has dual effects on the Ca(2+)-permeable AMPA receptor
      activity without affecting Ca(2+)-impermeable AMPA receptors.

PMID- 20045402
TI  - Procollagen I amino-terminal propeptide as a potential marker for multiple
      myeloma.
AB  - OBJECTIVES: Investigating relationship between bone markers, cytokines and
      conventional prognostic parameters in patients with multiple myeloma (MM) and to
      assess the clinical application of bone turnover markers. DESIGN AND METHODS:
      Sixty-four patients with MM were examined before treatment and followed for
      survival for over 7 years. Serum concentrations of bone markers and cytokines
      were determined by the Roche and R&D kits, respectively. Standard deviation
      scores (SDS) were employed to normalize values. RESULTS: Collagen fragments (beta
      CTX) were elevated in 47%, procollagen I amino-terminal propeptide (PINP)-in 28%,
      and osteocalcin (OC) in 11% of patients. The values of the SDS of PINP and OC,
      but not beta-CTX significantly decreased with MM stage. beta-CTX inversely
      correlated with vascular endothelial growth factor (VEGF) and albumin, and
      directly correlated with serum macrophage colony-stimulating factor (M-CSF). OC
      values correlated with albumin and beta2-microglobulin. PINP inversely correlated
      with LDH. The SDS values of PINP were significantly lower in MM patients with
      advanced bone disease. CONCLUSIONS: Circulating PINP concentration may be a
      useful marker for monitoring of treatment of multiple myeloma patients with bone
      lytic lesions, in particular, of patients treated with preoteasome inhibitors.

PMID- 20045403
TI  - Decrease in antioxidant status of plasma and erythrocytes from patients with
      ankylosing spondylitis.
AB  - OBJECTIVES: The aim of the study was to evaluate the antioxidant status in plasma
      and erythrocytes from patients with ankylosing spondylitis (AS). METHODS: 16
      patients with AS and 16 healthy volunteers were involved in this study.
      Activities of antioxidant enzymes: superoxide dismutase (SOD) and its isoenzymes 
      (SOD-Mn) and (SOD-ZnCu), catalase (CAT), glutathione peroxidase (GPx),
      glutathione reductase (GR) and glutathione transferase (GST), as well as the
      total antioxidant status (TAS) and concentration of malondialdehyde (MDA) in
      plasma and/or erythrocytes, respectively were determined. RESULTS: In patients
      with AS, a statistically significant decrease in plasma activity of SOD, SOD-CuZn
      and TAS, significant drop in activity of SOD, GPx, GST and GR in erythrocytes, as
      well as increased concentration of MDA in comparison with control group of
      healthy volunteers was observed. CONCLUSION: Decrease in antioxidant status
      leading to generation of oxidative stress may play an important role in the
      pathogenesis of ankylosing spondylitis.

PMID- 20045404
TI  - Discovery and characterization of a novel potent, selective and orally active
      inhibitor for mammalian ELOVL6.
AB  - The elongase of long chain fatty acids family 6 (ELOVL6) is a rate-limiting
      enzyme for the elongation of saturated and monounsaturated long chain fatty
      acids. ELOVL6 is abundantly expressed in lipogenic tissues such as liver, and its
      mRNA expression is up-regulated in obese model animals. ELOVL6 deficient mice are
      protected from high-fat-diet-induced insulin resistance, suggesting that ELOVL6
      might be a new therapeutic target for diabetes. We previously identified an
      indoledione compound, Compound A, as the first inhibitor for mammalian ELOVL6. In
      this study, we discovered a novel compound, Compound B, and characterized its
      biochemical and pharmacological properties. Compound B has a more appropriate
      profile for use as a pharmacological tool compared to Compound A. Chronic
      treatment with Compound B in model animals, diet-induced obesity (DIO) and KKAy
      mice, showed significant reduction in hepatic fatty acid composition, suggesting
      that it effectively inhibits ELOVL6 activity in the liver. However, no
      improvement in insulin resistance by ELOVL6 inhibition was found in these model
      animals. Further studies need to address the impact of ELOVL6 inhibition on
      pharmacological abnormalities in several model animals. This is the first report
      on pharmacology data from chronic studies using a selective ELOVL6 inhibitor.
      Compound B appears to be a useful tool to further understand the physiological
      roles of ELOVL6 and to evaluate the therapeutic potential of ELOVL6 inhibitors.

PMID- 20045405
TI  - The effect of local anesthetics on the inhibition of adult muscle-type nicotinic
      acetylcholine receptors by nondepolarizing muscle relaxants.
AB  - The primary action of local anesthetics is to inhibit voltage-gated Na(+)
      channels. However, local anesthetics also have an inhibitory effect on muscle
      type nicotinic acetylcholine receptors. Because local anesthetics could increase
      the neuromuscular blockade produced by nondepolarizing muscle relaxants, we
      investigated the interaction of local anesthetics with nondepolarizing muscle
      relaxants at adult muscle-type nicotinic acetylcholine receptors. This study
      tested the effects of lidocaine and procaine, alone and in combination with
      vecuronium and cisatracurium, on adult muscle-type nicotinic acetylcholine
      receptors. The adult mouse muscle-type nicotinic acetylcholine receptor was
      expressed in HEK293 cells and activated with 10microM acetylcholine. Currents
      were recorded using the whole-cell voltage-clamp technique. Adult muscle-type
      nicotinic acetylcholine receptors were potently inhibited by all the tested
      compounds. Although the potencies of procaine and lidocaine were statistically
      significantly different at adult muscle-type nicotinic acetylcholine receptors
      (50% inhibitory concentration values of 45.5microM and 11.1microM, respectively),
      procaine and lidocaine enhanced the inhibitory effect of nondepolarizing muscle
      relaxants at adult muscle-type nicotinic acetylcholine receptors to the same
      extent. The increased adult muscle-type nicotinic acetylcholine receptor
      inhibition produced when local anesthetics are combined with nondepolarizing
      muscle relaxants may contribute to the clinical enhancement of neuromuscular
      blockade by local anesthetics.

PMID- 20045406
TI  - beta2-Adrenoceptor, Gs and adenylate cyclase coupling in purified detergent
      resistant, low density membrane fractions.
AB  - Membrane rafts and caveolae are specialized microdomains of the cell membrane
      that form physical platforms for compartmentalization of signalling molecules.
      Here, we intended to gain insight into the consequences of caveolar localization
      in G protein-coupled receptor function. We analysed beta(2)-adrenoceptor
      signalling in purified CRLDF (caveolin-rich low density fractions) of beta(2)
      adrenoceptor-overexpressing HEK-293 cells. beta(2)-adrenoceptor and Gs
      immunoreactivities and forskolin-stimulated adenylate cyclase activity were all
      detected in CRLDF obtained by the conventional raft purification method that uses
      Triton X-100 solubilization. However, Triton X-100 caused a complete loss of the
      functional coupling between beta(2)-adrenoceptor, Gs and adenylate cyclase.
      Therefore, we developed an optimized purification method based on n-octyl-beta-d
      glucopyranoside solubilization, where the functional properties of beta(2)
      adrenoceptor, Gs and adenylate cyclase were preserved in the CRLDF. Using this
      method, we showed that isoproterenol-stimulated adenylate cyclase activity was
      similar in CRLDF and bulk membrane preparations of HEK-293 cells that overexpress
      beta(2)-adrenoceptor or beta(2)-adrenoceptor-Gs fusion. Accordingly, treatment of
      cells with methyl-beta-cyclodextrin, a caveola-disrupting agent, did not affect
      beta(2)-adrenoceptor-induced cAMP response. Likewise, these responses were
      insensitive to caveolin 1 and 2 overexpression. On the other hand, methyl-beta
      cyclodextrin treatment did decrease beta(2)-adrenoceptor-induced ERK
      phosphorylation. However, the latter effect of methyl-beta-cyclodextrin could be
      attributed to a non-specific effect rather than its ability to disrupt membrane
      microdomains. We showed that localization in the raft microdomains did not affect
      the signalling efficiency of beta(2)-adrenoceptor-Gs-adenylate cyclase pathway,
      and that methyl-beta-cyclodextrin may inhibit signalling by directly affecting
      the signalling system independently of its caveola-disrupting property.

PMID- 20045407
TI  - Immune cell profile in invasive cholesteatomas: preliminary findings.
AB  - BACKGROUND: Cholesteatoma consists of keratinizing squamous epithelium,
      granulation tissue and keratin plugs. The pathogenesis of cholesteatoma may be
      related to alterations in the stromal immune cell infiltrate. OBJECTIVE: To
      examine the immunophenotypic characteristics of the immune cell infiltrate in
      invasive cholesteatomas. MATERIALS AND METHODS: This study included 12 patients
      with invasive cholesteatomas causing wide bone erosion of the mastoid, middle ear
      structures, and the bony plates of middle ear cleft. Diagnosis of invasiveness
      was based on the clinical, radiological and intraoperative findings. Canal wall
      down surgical approach was done in all cases to control the disease process. We
      used the cholesteatomatous tissue specimens to perform immunohistochemical stains
      for B cells (CD20), T cells (CD3), histiocytes (CD68) and Langerhans' cells
      (CD1a). Mouse monoclonal antibodies and immunoperoxidase staining methods were
      used. The results of immunohistology were scored as mean values of positively
      stained immune cells. The data were compared with findings in 10 specimens of
      external ear skin (control group). RESULTS: Immunohistochemistry showed highly
      significant (p<0.00) counts of immune cells in invasive cholesteatomas (CD3:
      4.7+/-0.4, CD68:4.6+/-0.5, CD20: 0.8+/-0.1 and CD1a: 0.8 +/-0.1) compared to
      those in external canal skin (control group: CD3:0.8+/-0.3, CD68: 1.0+/-0.4,
      CD20: 0.2+/-0.1 and CD1a: 0.1+/-0.1). In cholesteatomas, the predominant of
      CD3(+) T lymphocytes and CD68(+) cells (histiocytes). Rare CD20(+) cells and
      CD1a(+) cells (Langerhans' cells) were also observed. CONCLUSIONS: This
      preliminary study describes the profile of the immune cell infiltrate in invasive
      cholesteatomas. The numeric dominance of CD3(+) cells and CD68(+) cells suggests
      that cell-mediated immunity has important role in the development of
      cholesteatoma and in its autodestructive properties. Further studies are
      recommended to categorize the T cell subsets in different stages of
      cholesteatomas.

PMID- 20045408
TI  - Assessment of housekeeping genes for use in normalization of real time PCR in
      skeletal muscle with chronic degenerative changes.
AB  - The real time PCR technique requires the normalization of the gene of interest to
      reference genes that are accepted to be ubiquitously expressed. The choice of the
      reference gene(s) needs to be determined by researchers according to the
      particular tissue or model of interest. The best normalization gene is not easy
      to decide, particularly if the investigated tissue displays architectural changes
      and structural reorganization. We have investigated the expression of four
      housekeeping genes that are widely used for the normalization purposes (TATA
      binding protein, beta actin, hypoxanthine-guanine phosphorybosyl transferase and
      glyceraldehyde-3-phosphate dehydrogenase) in a skeletal muscle degeneration model
      applied by the release of the Achilles tendon which leads to a time-course
      degeneration of the soleus and gastrocnemius muscles. This study indicates that
      the TATA binding protein and the beta actin gene to be the least effected in the
      course of degeneration induced by tenotomy in rat soleus and gastrocnemius
      muscle.

PMID- 20045409
TI  - Critical period for the whisker-barrel system.

PMID- 20045410
TI  - Sleep deprivation attenuates experimental stroke severity in rats.
AB  - Indirect epidemiological and experimental evidence suggest that the severity of
      injury during stroke is influenced by prior sleep history. The aim of our study
      was to test the effect of acute sleep deprivation on early outcome following
      experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to
      focal cerebral ischemia by reversible right middle cerebral artery occlusion
      (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep
      deprivation (TSD) by "gentle handling", whereas the other rats served as
      controls. Neurological function during the first week after stroke was monitored
      using a battery of behavioral tests investigating the asymmetry of sensorimotor
      deficit (tape removal test and cylinder test), bilateral sensorimotor
      coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze).
      Following MCAO, control rats had impaired behavioral performance in all tests.
      The largest impairment was noted in the tape test where the tape removal time
      from the left forelimb (contralateral to MCAO) was increased by approximately 10
      fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of
      sensorimotor performance consistent with a 2.5 fold smaller infarct volume and
      reduced morphological signs of neuronal injury at day 7 after MCAO. Our data
      suggest that brief TSD induces a neuroprotective response that limits the
      severity of a subsequent stroke, similar to rapid ischemic preconditioning.

PMID- 20045411
TI  - Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle
      and promotes nerve regeneration in a rat sciatic nerve injury model.
AB  - Methylcobalamin is a vitamin B12 analog and is necessary for the maintenance of
      the nervous system. Although some previous studies have referred to the effects
      of methylcobalamin on neurons, the precise mechanism of this effect remains
      obscure. Here we show that methylcobalamin at concentrations above 100 nM
      promotes neurite outgrowth and neuronal survival and that these effects are
      mediated by the methylation cycle, a metabolic pathway involving methylation
      reactions. We also demonstrate that methylcobalamin increases Erk1/2 and Akt
      activities through the methylation cycle. In a rat sciatic nerve injury model,
      continuous administration of high doses of methylcobalamin improves nerve
      regeneration and functional recovery. Therefore, methylcobalamin may provide the
      basis for better treatments of nervous disorders through effective systemic or
      local delivery of high doses of methylcobalamin to target organs.

PMID- 20045412
TI  - Hippocampal neurovascular and hypothalamic-pituitary-adrenal axis alterations in
      spontaneously type 2 diabetic GK rats.
AB  - Metabolic and vascular consequences of diabetes mellitus induce several CNS
      complications. The dentate gyrus of the hippocampus, a well-recognized target for
      diabetic alterations, is a neurogenic area associated with memory and learning
      processes. Here, we explored the hippocampal neurogenesis and its
      microenvironment (astrocytes, vascularisation and glucocorticoid influence) in a
      spontaneous model of type 2 diabetes, the Goto-Kakizaki rat. The number of
      proliferative Ki67(+) cells and young doublecortin(+) neurons was 2-fold higher
      in the hippocampus from diabetic rats than in normoglycemic control Wistar at 4
      months of age. However, there was no difference in cell survival, studied 3 weeks
      after bromodeoxyuridine administration. Labeling of endothelial cells against von
      Willebrand factor, demonstrated a 50% decrease in the granular cell layer
      fractional area covered by blood vessels and a diminished capillary branching in
      diabetic rats. Finally, Goto-Kakizaki rats exhibited decreased glucocorticoid
      receptor immunolabeling in CA1, associated with higher corticosteronemia. In
      conclusion, diabetic rats showed increased cell proliferation and neuronal
      differentiation without concomitant survival modification. A high proliferation
      rate, potentially reflecting a compensatory mechanism for neuronal suffering,
      also exists in various pathological situations. However, endothelial alteration
      induced by chronic hyperglycemia, hyperleptinemia and insulin resistance and
      associated with deleterious glucocorticoid effects might impair effective
      neurogenesis in diabetic Goto-Kakizaki rats.

PMID- 20045413
TI  - What happens when we get angry? Hormonal, cardiovascular and asymmetrical brain
      responses.
AB  - This study aimed to evaluate neuroendocrine and cardiovascular responses together
      with changes in brain asymmetry following an anger mood induction laboratory
      task. Previous research has shown an increase in heart rate and blood pressure
      when anger is experienced. Increased testosterone and decreased cortisol in
      response to anger and aggressive behavior have also been reported. With regard to
      asymmetrical frontal brain activity and emotion, the valence model links negative
      affect (as anger) to the right hemisphere while the motivational direction model
      links approach-related emotions (as anger) to the left hemisphere. From the
      subjective perception and from the neuroendocrine and cardiovascular response of
      the subjects, we can conclude that the self-referent statement anger induction
      method by Engebretson et al. (1999) was able to generate an experience of an
      anger affect in 30 healthy men. Another question was to analyze the consequences
      of that experience upon perceptual asymmetry when measured with a non-emotional
      laterality task. Regarding dichotic listening, an enhanced REA (right ear
      advantage) was observed after anger which indicates greater left hemisphere
      activity, supporting the motivational direction model.

PMID- 20045414
TI  - Potentiated effect of systemic administration of oxytocin on hypertonic NaCl
      intake in food-deprived male rats.
AB  - Subcutaneous administration of oxytocin (OT) increases water intake and
      sodium/urine excretion in food-deprived male rats. This study analyzes the effect
      of OT administration (at 0830 and 1430h) on the consumption of water and
      hypertonic NaCl (1.5%). In the first experiment, injections of OT increased the
      intake of hypertonic NaCl (but not of water) in food-deprived rats but not in ad
      lib-fed animals during the second 12 h (2030 to 0830) of the treatment day. The
      net concentration of the fluid consumed by OT/deprived animals was close to
      isotonic. In the second experiment, the initial effect of OT administration was
      an increase in urine volume and urinary sodium excretion and concentration by
      food-deprived animals during the first 12 h (0830 to 2030). These findings
      suggest that in food-deprived animals, systemic administration of OT induces NaCl
      intake as a consequence of previous urine loss and urinary sodium excretion.

PMID- 20045415
TI  - Interrupted catalysis: the EF4 (LepA) effect on back-translocation.
AB  - EF4, although structurally similar to the translocase EF-G, promotes back
      translocation of tRNAs on the ribosome and is important for bacterial growth
      under certain conditions. Here, using a coordinated set of in vitro kinetic
      measures, including changes in the puromycin reactivity of peptidyl-tRNA and in
      the fluorescence of labeled tRNAs and mRNA, we elucidate the kinetic mechanism of
      EF4-catalyzed back-translocation and determine the effects of the translocation
      inhibitors spectinomycin and viomycin on the process. EF4-dependent back
      translocation proceeds from a post-translocation (POST) complex to a pre
      translocation (PRE) complex via a four-step kinetic scheme (i.e., POST-->I(1)-
      >I(2)-->I(3)-->PRE, which is not the simple reverse of translocation). During
      back-translocation, movements of the tRNA core regions and of mRNA are closely
      coupled to one another but are sometimes decoupled from movement of the 3'-end of
      peptidyl-tRNA. EF4 may be thought of as performing an interrupted catalysis of
      back-translocation, stopping at the formation of I(3) rather than catalyzing the
      complete process of back-translocation culminating in PRE complex formation. The
      delay in polypeptide elongation resulting from transient accumulation of I(3) is
      likely to be important for optimizing functional protein biosynthesis.

PMID- 20045416
TI  - Engineering fully human monoclonal antibodies from murine variable regions.
AB  - Fully human monoclonal antibodies (mAbs) derived from transgenic mice or human
      antibody libraries are the current state of the art for reducing the
      immunogenicity risk of antibody drugs. Here, we describe a novel method for
      generating fully human mAbs from nonhuman variable regions using information from
      the human germline repertoire. Central to our strategy is the rational
      engineering of residues within and proximal to CDRs and the V(H)/V(L) interface
      by iteratively exploring substitutions to the closest human germline sequences
      using semi-automated computational methods. Starting from the parent murine
      variable regions of three currently marketed mAbs targeting CD25, vascular
      endothelial growth factor, and tumor necrosis factor alpha, we have generated
      fully human antibodies with 59, 46, and 45 substitutions, respectively, compared
      to the parent murine sequences. A large number of these substitutions were in the
      CDRs, which are typically avoided in humanization methods. Antigen affinities of
      the fully human variants were comparable to the chimeric mAbs in each case.
      Furthermore, in vitro functional characterization indicated that all retain
      potency of the chimeric mAbs and have comparable activity to their respective
      marketed drugs daclizumab, bevacizumab, and infliximab. Based on local and global
      sequence identity, the sequences of our engineered mAbs are indistinguishable
      from those of fully human mAbs isolated from transgenic mice or human antibody
      libraries. This work establishes a simple rational engineering methodology for
      generating fully human antibody therapeutics from murine mAbs produced from
      standard hybridoma technology.

PMID- 20045417
TI  - In vivo and in vitro application of black soybean peptides in the amelioration of
      endoplasmic reticulum stress and improvement of insulin resistance.
AB  - AIMS: Hepatic endoplasmic reticulum (ER) stress plays a key role in the
      development of obesity-induced insulin resistance. This study evaluated the
      effects of peptides from black soybean (BSP) on ER stress and insulin signaling
      in vitro and in vivo. MAIN METHODS: Using C2C12 myotubes or HepG2 cells, we
      evaluated the effects of BSP on the expression of proteins involved in insulin
      signaling and in the ER stress response in insulin-sensitive or insulin-resistant
      cells. BSP was given orally to db/db mice for 5weeks to investigate its
      antidiabetic effects in vivo and the underlying mechanisms. KEY FINDINGS: BSP
      increased GLUT4 translocation and glucose transport in myotubes and stimulated
      Akt-mediated glycogen synthase kinase-3beta (GSK-3beta) and Foxo1 phosphorylation
      in HepG2 cells. BSP significantly restored the suppression of insulin-mediated
      Akt phosphorylation in insulin-resistant cells. BSP significantly inhibited the
      activation of ER stress-responsive proteins by thapsigargin. BSP also
      significantly reduced blood glucose and improved glucose tolerance in db/db mice.
      The serum lipid profile (triglyceride and high-density lipoprotein
      concentrations) improved concomitantly with the BSP-induced downregulation of
      hepatic fatty acid synthase expression in db/db mice. Consistent with the results
      observed in HepG2 cells, BSP downregulated the elevated hepatic ER stress
      response in diabetic mice concomitantly with an increased expression of phospho
      Foxo1. SIGNIFICANCE: A peptide mixture, BSP, showed beneficial effects through
      multiple mechanisms involving the suppression of hepatic ER stress and
      restoration of insulin resistance, suggesting that it has potential as an
      antidiabetic agent.

PMID- 20045418
TI  - Novel folate binding protein-1 interactions in embryonic orofacial tissue.
AB  - AIM: To identify proteins with which FolBp1 may interact within lipid rafts in
      tissue derived from embryonic orofacial tissue. METHODS: A yeast two-hybrid
      screen of a cDNA library, derived from orofacial tissue from gestational day 11
      to 13 mouse embryos, was conducted. KEY FINDINGS: Using the full-length FolBp1
      protein as bait, two proteins that bind FolBp1 were identified, Bat2d, and a
      fibronectin type III-containing domain protein. Results were confirmed by
      glutathione S-transferase pull-down assays. SIGNIFICANCE: As a component of
      membrane lipid raft protein complexes, these binding proteins may represent
      "helper" or chaperone proteins that associate with FolBp1 in order to facilitate
      the transport of folate across the plasma membrane. The protein-protein
      interactions detected, while limited in number, may be critical in mediating the
      role of FolBp1 in folate transport, particularly in the developing embryo.

PMID- 20045419
TI  - Foreword from the organizers.

PMID- 20045421
TI  - Intragastric infusion of glucose enhances the rewarding effect of sorbitol fatty
      acid ester ingestion as measured by conditioned place preference in mice.
AB  - We investigated substances that induce a rewarding effect during the
      postingestive process using the conditioned place preference (CPP) test. Although
      mice showed high affinity for a low-energy fat substitute--sorbitol fatty acid
      esters and low-concentration linoleic acid solution--they did not exhibit a place
      preference toward a voluntary intake of fat substitute in the CPP test. However,
      during a conditioning session of CPP that involved intragastric administration of
      corn oil immediately before the intake of the fat substitute, the test mice
      displayed a place preference. Similarly, intragastric administration of glucose,
      galactose, and dextrin also induced CPP; however, fructose, mannose, and a
      nonmetabolized carbohydrate did not. These results suggest that administration of
      corn oil and glucose has the same postingestive effect with regard to inducing
      CPP and that the structural specificity of carbohydrates influences the
      postingestive effect.

PMID- 20045420
TI  - Primary brain tumors, neural stem cell, and brain tumor cancer cells: where is
      the link?
AB  - The discovery of brain tumor-derived cells (BTSC) with the properties of stem
      cells has led to the formulation of the hypothesis that neural stem cells could
      be the cell of origin of primary brain tumors (PBT). In this review we present
      the most common molecular changes in PBT, define the criteria of identification
      of BTSC and discuss the similarities between the characteristics of these cells
      and those of the endogenous population of neural stem cells (NPCs) residing in
      germinal areas of the adult brain. Finally, we propose possible mechanisms of
      cancer initiation and progression and suggest a model of tumor initiation that
      includes intrinsic changes of resident NSC and potential changes in the
      microenvironment defining the niche where the NSC reside.

PMID- 20045423
TI  - Patterns of beverage use across the lifecycle.
AB  - Total beverage intake patterns have changed greatly over the past half century.
      The present research was conducted to evaluate historic and current patterns of
      beverage consumption of adults and children in the U.S. Data were drawn from food
      balance surveys along with two-day beverage intake averages and were weighted to
      be nationally representative. A marked slow continuous shift downward in total
      milk intake with a shift toward an increased proportion of reduced fat milk was
      determined. The biggest shifts in beverage consumption among children aged 2 to18
      were an increase in sugar-sweetened beverages (SSBs) (from 87 to 154kcal/d), a
      smaller increase in juices (+21kcal/d), and a decrease in milk consumption (
      91kcal/d). Data among adults aged 19 and older indicated that SSB intake has more
      than doubled. Water intake was highly variable, with a marked increase in bottled
      water intake but no clear trend in total water intake. Overall trends by age were
      presented and indicated that age-related beverage intake, both in ounces and
      kcal/day, decreased sharply for adults aged 60 and older. Kcal/d values ranged
      from a low of 283 for those over age 60 to a peak of 533 for those aged 19 to39
      to 367 for 2 to 6year olds. The consumer shift toward increased levels of SSBs
      and alcohol, limited amounts of reduced fat milk along with a continued
      consumption of whole milk, and increased juice intake represent issues to address
      from a public health perspective.

PMID- 20045422
TI  - Repeated exposure attenuates the behavioral response of rats to static high
      magnetic fields.
AB  - Exposure of rats to high strength static magnetic fields of 7 T or above has
      behavioral effects such as the induction of locomotor circling, the suppression
      of rearing, and the acquisition of conditioned taste aversion (CTA). To determine
      if habituation occurs across magnetic field exposures, rats were pre-exposed two
      times to a 14 T static magnetic field for 30 min on two consecutive days; on the
      third day, rats were given access to a novel 0.125% saccharin prior to a third 30
      min exposure to the 14 T magnetic field. Compared to sham-exposed rats, pre
      exposed rats showed less locomotor circling and an attenuated CTA. Rearing was
      suppressed in all magnet-exposed groups regardless of pre-exposure, suggesting
      that the suppression of rearing is more sensitive than other behavioral responses
      to magnet exposure. Habituation was also observed when rats underwent pre
      exposures at 2-3h intervals on a single day. Components of the habituation were
      also long-lasting; a diminished circling response was observed when rats were
      exposed to magnetic field 36 days after 2 pre-exposures. To control for possible
      effects of unconditioned stimulus pre-exposure, rats were also tested in a
      similar experimental design with two injections of LiCl prior to the pairing of
      saccharin with a third injection of LiCl. Pre-exposure to LiCl did not attenuate
      the LiCl-induced CTA, suggesting that 2 pre-exposures to an unconditioned
      stimulus are not sufficient to explain the habituation to magnet exposure.
      Because the effects of magnetic field exposure are dependent on an intact
      vestibular apparatus, and because the vestibular system can habituate to many
      forms of perturbation, habituation to magnetic field exposure is consistent with
      mediation of magnetic field effects by the vestibular system.

PMID- 20045424
TI  - Cognitive and social functions and growth factors in a mouse model of Rett
      syndrome.
AB  - Rett syndrome (RTT) is an autism-spectrum disorder caused by mutations in the X
      linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormalities in
      social behavior, stereotyped movements, and restricted interests are common
      features in both RTT and classic autism. While mouse models of both RTT and
      autism exist, social behaviors have not been explored extensively in mouse models
      of RTT. Here, we report cognitive and social abnormalities in Mecp2(1lox) null
      mice, an animal model of RTT. The null mice show severe deficits in short- and
      long-term object recognition memories, reminiscent of the severe cognitive
      deficits seen in RTT girls. Social behavior, however, is abnormal in that the
      null mice spend more time in contact with stranger mice than do wildtype
      controls. These findings are consistent with reports of increased reciprocal
      social interaction in RTT girls relative to classic autism. We also report here
      that the levels of the neurotrophins brain-derived neurotrophic factor (BDNF),
      insulin-like growth factor-1 (IGF-1), and nerve growth factor (NGF) are decreased
      in the hippocampus of the null mice, and discuss how this may provide an
      underlying mechanism for both the cognitive deficits and the increased motivation
      for social contact observed in the Mecp2(1lox) null mice. These studies support a
      differential etiology between RTT and autism, particularly with respect to
      sociability deficits.

PMID- 20045425
TI  - One day of food restriction does not result in an increase in subsequent daily
      food intake in humans.
AB  - The purpose of this study was to examine the effect of one day of food
      restriction on subsequent spontaneous daily food intake and the recovery of body
      weight in humans. Twenty-two, non-restrained females were fed from Monday to
      Friday for four weeks using food prepared and measured in the Cornell Metabolic
      Laboratory. For the first week, all participants ate ad libitum. For each
      subsequent Monday, participants were divided into three groups in which either
      they (a) ate ad libitum, (b) were restricted to eating 1200 kcal (5040 kj), or
      (c) were fasted. From Tuesday until Friday participants ate ad libitum. During
      each session, all food consumed as well as body weight were measured. Body weight
      did not change following the day of ad libitum eating, but decreased
      significantly after the day of food restriction decreasing still further after
      fasting, indicating high compliance with study protocol. Although the loss in
      body weight was regained within four days, the recovery was accomplished without
      any increase in spontaneous food intake. Although no direct measurement of energy
      expenditure was made in this study, the results strongly suggest that decreases
      in metabolic rate play a more dominant role in the recovery of body weight
      following food restriction than the control of food intake.

PMID- 20045426
TI  - Photoperiodic modulation of reproductive physiology and behaviour in the cichlid
      fish Cichlasoma dimerus.
AB  - Timing of breeding to an optimal season is a requirement for a successful
      reproductive outcome in seasonally breeding species. Photoperiodic signals are
      capable of modifying the reproductive behaviour and reproductive systems in
      several vertebrate species. The cichlid fish Cichlasoma dimerus shows highly
      organized breeding activities and different social status. The aim of this study
      is to test whether C. dimerus reproductive behaviour (male aggressive behaviour
      and female choice) and reproductive physiology (GnRH3 morphometric parameters,
      pituitary hormones content and organ-somatic indexes) are modulated by
      photoperiod. Before spawning, dominant pairs were isolated and kept in opposite
      tanks of 20 l for one week, so they could see each other but not physically
      interact. Afterwards, a group was exposed for four weeks to a short photoperiod
      (8h light:16 h dark) (short photoperiod exposed animals: SP) while another group
      was exposed to a long photoperiod (14 h light:10h dark) (long photoperiod exposed
      animals: LP). Temperature was maintained constant. Behavioural experiments showed
      that male aggression related to territory selection and its defence is reduced in
      SP males. Further, SP females were never chosen. At the brain level we
      demonstrated that GnRH3 neuronal optical density of staining was reduced.
      Finally, at the pituitary level we showed that SP males showed low levels of beta
      LH, PRL and GH in the pituitary, and that SP females showed no significant
      differences in the pituitary content of any hormone. Taken all together these
      results suggest that in C. dimerus the photoperiod is a relevant environmental
      cue related to reproductive behaviour and physiology.

PMID- 20045427
TI  - Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and
      children with different genotypes and haplotypes.
AB  - The paraoxonase 1 (PON1) enzyme prevents low-density lipoprotein oxidation and
      also detoxifies the oxon derivatives of certain neurotoxic organophosphate (OP)
      pesticides. PON1 activity in infants is low compared to adults, rendering them
      with lower metabolic and antioxidant capacities. We made a longitudinal
      comparison of the role of genetic variability on control of PON1 phenotypes in
      Mexican-American mothers and their children at the time of delivery (n=388 and
      338, respectively) and again 7 years later (n=280 and 281, respectively) using
      generalized estimating equations models. At age 7, children's mean PON1
      activities were still lower than those of mothers. This difference was larger in
      children with genotypes associated with low PON1 activities (PON1(-108TT),
      PON1(192QQ), and PON1(-909CC)). In mothers, PON1 activities were elevated at
      delivery and during pregnancy compared to 7 years later when they were not
      pregnant (p<0.001). In non-pregnant mothers, PON1 polymorphisms and haplotypes
      accounted for almost 2-fold more variation of arylesterase (AREase) and
      chlorpyrifos-oxonase (CPOase) activity than in mothers at delivery. In both
      mothers and children, the five PON1 polymorphisms (192, 55, -108, -909, -162)
      explained a noticeably larger proportion of variance of paraoxonase activity (62
      78%) than AREase activity (12.3-26.6%). Genetic control of PON1 enzymatic
      activity varies in children compared to adults and is also affected by pregnancy
      status. In addition to known PON1 polymorphisms, unidentified environmental,
      genetic, or epigenetic factors may also influence variability of PON1 expression
      and therefore susceptibility to OPs and oxidative stress.

PMID- 20045428
TI  - Physiologically based pharmacokinetic modeling of dibromoacetic acid in F344
      rats.
AB  - A novel physiologically based pharmacokinetic (PBPK) model structure, which
      includes submodels for the common metabolites (glyoxylate (GXA) and oxalate
      (OXA)) that may be involved in the toxicity or carcinogenicity of dibromoacetic
      acid (DBA), has been developed. Particular attention is paid to the
      representation of hepatic metabolism, which is the primary elimination mechanism.
      DBA-induced suicide inhibition is modeled by irreversible covalent binding of the
      intermediate metabolite alpha-halocarboxymethylglutathione (alphaH1) to the
      glutathione-S-transferase zeta (GSTzeta) enzyme. We also present data
      illustrating the presence of a secondary non-GSTzeta metabolic pathway for DBA,
      but not dichloroacetic acid (DCA), that produces GXA. The model is calibrated
      with plasma and urine concentration data from DBA exposures in female F344 rats
      through intravenous (IV), oral gavage, and drinking water routes. Sensitivity
      analysis is performed to confirm identifiability of estimated parameters.
      Finally, model validation is performed with data sets not used during
      calibration. Given the structural similarity of dihaloacetates (DHAs), we
      hypothesize that the PBPK model presented here has the capacity to describe the
      kinetics of any member or mixture of members of this class in any species with
      the alteration of chemical-and species-specific parameters.

PMID- 20045429
TI  - Fullerene derivatives induce premature senescence: a new toxicity paradigm or
      novel biomedical applications.
AB  - Engineered fullerenes (C(60)) are extensively used for commercial and clinical
      applications based on their unique physicochemical properties. Such materials
      have also been recognized as byproducts of many industrial activities.
      Functionalization of C(60) may significantly influence the nature of its
      interactions with biological systems, impacting its applications and raising
      uncertainties about its health effects. In the present study, we compared the
      bioimpact of two chemically modified fullerene derivatives, hexa carboxyl
      fullerene adduct (Hexa-C(60)) and tris carboxyl fullerene adduct (tris-C(60)) to
      pristine fullerene C(60) encapsulated with gamma (gamma)-cyclodextrin C(60) (CD
      C(60)), using human cutaneous epithelial cells (HEK) to simulate possible
      applications and occupational dermal exposure route. We report, for the first
      time, the discovery of premature senescence as a potential endpoint of
      nanomaterial elicited biological effects, providing a new paradigm for
      nanoparticle-induced toxicity in human cells. Moreover, this response appeared to
      be functionalization specific, in that, only tris-C(60) induced senescence. We
      investigated key biological responses, such as cellular viability, intracellular
      ROS generation, cell proliferation and cell cycle responses. Our results indicate
      that the often observed 'anti-apoptotic' function of fullerene derivatives may be
      independent of their 'ROS scavenging' role as previously reported. We discovered
      that the tris-C(60)-induced responses were associated with G(0)/G(1) cell cycle
      arrest and cellular senescence. On further evaluation of the molecular mechanisms
      underlying the senescent response, a significant decrease in the expression
      levels of HERC5 was noted. HERC5 is a ubiquitin ligase of the HERC family and is
      implicated to be involved in innate immune responses to viral and bacterial
      infections.

PMID- 20045431
TI  - Evaluation of deltamethrin kinetics and dosimetry in the maturing rat using a
      PBPK model.
AB  - Immature rats are more susceptible than adults to the acute neurotoxicity of
      pyrethroid insecticides like deltamethrin (DLM). A companion kinetics study (Kim
      et al., in press) revealed that blood and brain levels of the neuroactive parent
      compound were inversely related to age in rats 10, 21, 40 and 90 days old. The
      objective of the current study was to modify a physiologically based
      pharmacokinetic (PBPK) model of DLM disposition in the adult male Sprague-Dawley
      rat (Mirfazaelian et al., 2006), so blood and target organ dosimetry could be
      accurately predicted during maturation. Age-specific organ weights and age
      dependent changes in the oxidative and hydrolytic clearance of DLM were modeled
      with a generalized Michaelis-Menten model for growth and the summary equations
      incorporated into the PBPK model. The model's simulations compared favorably with
      empirical DLM time-courses in plasma, blood, brain and fat for the four age
      groups evaluated (10, 21, 40 and 90 days old). PND 10 pups' area under the 24-h
      brain concentration time curve (AUC(0-24h)) was 3.8-fold higher than that of the
      PND 90 adults. Our maturing rat PBPK model allows for updating with age- and
      chemical-dependent parameters, so pyrethroid dosimetry can be forecast in young
      and aged individuals. Hence, this model provides a methodology for risk assessors
      to consider age-specific adjustments to oral Reference Doses on the basis of PK
      differences.

PMID- 20045432
TI  - Venom neutralization by purified bioactive molecules: Synthetic peptide
      derivatives of the endogenous PLA(2) inhibitory protein PIP (a mini-review).
AB  - Envenomation due to snakebite constitutes a significant public health problem in
      tropical and subtropical countries. Antivenom therapy is still the mainstay of
      treatment for snake envenomation, and yet despite recent research focused on the
      prospects of using antivenom adjuncts to aid in serotherapy, no new products have
      emerged so far for therapeutic use. Various methodologies including molecular
      biology, crystallography, functional and morphological approaches, etc., are
      employed in the search for such inhibitors with a view to generate molecules that
      can stop partially or completely the activities of toxic phospholipase A(2)
      (PLA(2)) and snake venom metalloproteinase (SvMPs) enzymes at the molecular
      level. Herein, both natural and synthetic inhibitors derived from a variety of
      sources including medicinal plants, mammals, marine animals, fungi, bacteria, and
      from the venom and blood of snakes have been briefly reviewed. Attention has been
      focused on the snake serum-based phospholipase A(2) inhibitors (PLIs),
      particularly on the PLI derived from python snake serum (PIP), highlighting the
      potential of the natural product, PIP, or possible derivatives of it, as a
      complementary treatment to serotherapy against the inflammation and/or muscle
      damaging activity of snake venoms. The data indicate a more efficient pathway for
      inhibition and blocking the activity of PLA(2)s and matrix metalloproteinases
      (MMPs), thus representing a feasible complementary treatment for snakebites. Such
      information may be helpful for interfering on the biological processes that these
      molecules are involved in human inflammatory-related diseases, and also for the
      development of new drugs for treatment of snake envenomation.

PMID- 20045430
TI  - Low level exposure to monomethyl arsonous acid-induced the over-production of
      inflammation-related cytokines and the activation of cell signals associated with
      tumor progression in a urothelial cell model.
AB  - Human bladder cancer has been associated with chronic exposure to arsenic.
      Chronic exposure of an immortalized non-tumorigenic urothelial cell line (UROtsa
      cells) to arsenicals has transformed these cells to a malignant phenotype, but
      the involved mechanisms are not fully understood. Chronic inflammation has been
      linked with cancer development mainly because many pro-inflammatory cytokines,
      growth factors as well as angiogenic chemokines have been found in tumors. In
      this study the chronology of inflammatory cytokines production was profiled in
      UROtsa cells chronically exposed to the toxic arsenic metabolite,
      monomethylarsonous acid [50 nM MMA(III)] to know the role of inflammation in cell
      transformation. Acute 50 nM MMA(III) exposure induced over-production of many pro
      inflammatory cytokines as soon as 12 h after acute exposure. The same cytokines
      remain over-regulated after chronic exposure to 50 nM MMA(III), especially after
      3 mo exposure. At 3 mo exposure the sustained production of cytokines like IL-1,
      IL-6, IL-8 and TNF is coincident with the appearance of characteristics
      associated with cell transformation seen in other arsenic-UROtsa studies. The
      sustained and increased activation of NFkappaB and c-Jun is also present along
      the transformation process and the phosphorylated proteins p38 MAPK and ERK 1/2
      are increased also through the time line. Taken together these results support
      the notion that chronic inflammation is associated within MMA(III)-induced cell
      transformation and may act as a promoting factor in UROtsa cell transformation.

PMID- 20045433
TI  - Identification of substrates for cyclin dependent kinases.

PMID- 20045434
TI  - Involvement of serotonin neurotransmission in hippocampal neurogenesis and
      behavioral responses in a rat model of post-stroke depression.
AB  - Ischemia-stimulated dentate gyrus (DG) neurogenesis is hypothesized to be an
      etiological factor of post-stroke depression (PSD) and a potential target of
      selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in
      PSD. Clinical investigations have explored the strategy of augmenting SSRIs
      action by combination with a 5-HT1A receptor antagonist. We investigated the
      relative importance of the effects on ischemia-stimulated neurogenesis and
      depressive-like behavior of WAY-100635 versus citalopram at different dose levels
      in PSD animals. Adult rats were exposed to a chronic mild stress paradigm after
      ischemic surgery. Decreased sucrose consumption was indicative of the core
      depressive syndrome anhedonia. Proliferating cells and their fate were monitored
      by bromodeoxyuridine labeling protocols up to 28 days after ischemia. Expression
      of the 5-HT1A receptor in DG was also examined. The current findings confirmed
      the ability of WAY-100635 to augment SSRIs pharmacological efficacy and SSRIs
      induced elevation of post-stroke DG neurogenesis. Specifically, WAY-100635 and
      citalopram in different dose combinations display their relative importance in
      ischemia-stimulated neurogenesis probably through reinforcing serotonergic
      neurotransmission and/or density of 5-HT1A receptor in DG. The present data
      extend our understanding that increase of ischemia-induced DG neurogenesis can be
      interpreted as a valid index, to an extent, or even a prerequisite for an
      efficient co-treatment strategy.

PMID- 20045435
TI  - Biochemical and biophysical characterisation of DBL1alpha1-varO, the rosetting
      domain of PfEMP1 from the VarO line of Plasmodium falciparum.
AB  - Rosetting of erythrocytes infected with Plasmodium falciparum is frequently
      observed in children with severe malaria. This adhesion phenomenon has been
      linked to the DBL1alpha domain of P. falciparum erythrocyte membrane protein 1
      (PfEMP1) in three laboratory clones: FCR3S1.2, IT4R29 and Palo Alto varO. Here,
      we compare the soluble recombinant NTS-DBL1alpha(1)-varO domain (NTS: N-terminal
      segment) obtained from E. coli, Pichia pastoris and baculovirus/insect cell
      expression systems. In each case, the presence of NTS was necessary for obtaining
      a soluble product. Successful expression in E. coli required maltose-binding
      protein as an N-terminal fusion partner. Each expression system produced an
      identical, correctly folded protein, as judged by biochemical and biophysical
      characterisations, and by the capacity to elicit antibodies that react with the
      surface of VarO-infected erythrocytes and disrupt VarO rosettes. Binding studies
      using surface plasmon resonance (SPR) techniques showed that NTS-DBL1alpha(1)
      produced in E. coli binds to heparin with micromolar affinity. IC(50) constants
      for other sulphated oligosaccharides were determined using SPR by measuring their
      competitive binding to the soluble protein in the presence of immobilized
      heparin. The affinity to NTS-DBL1alpha(1) was related to the degree of sulphation
      of the oligosaccharide, although the position of the sulphate groups on the sugar
      rings was also important. VarO rosettes could be disrupted by sulphated
      oligosaccharides with an efficacy that correlated with their binding affinity to
      recombinant NTS-DBL1alpha(1). Thus high yields of soluble NTS-DBL1alpha(1) with
      native conformation have been produced, opening novel perspectives for both
      structure-function studies and vaccine development.

PMID- 20045436
TI  - Structure of Trypanosoma brucei glutathione synthetase: domain and loop
      alterations in the catalytic cycle of a highly conserved enzyme.
AB  - Glutathione synthetase catalyses the synthesis of the low molecular mass thiol
      glutathione from l-gamma-glutamyl-l-cysteine and glycine. We report the crystal
      structure of the dimeric enzyme from Trypanosoma brucei in complex with the
      product glutathione. The enzyme belongs to the ATP-grasp family, a group of
      enzymes known to undergo conformational changes upon ligand binding. The T.
      brucei enzyme crystal structure presents two dimers in the asymmetric unit. The
      structure reveals variability in the order and position of a small domain, which
      forms a lid for the active site and serves to capture conformations likely to
      exist during the catalytic cycle. Comparisons with orthologous enzymes, in
      particular from Homo sapiens and Saccharomyces cerevisae, indicate a high degree
      of sequence and structure conservation in part of the active site. Structural
      differences that are observed between the orthologous enzymes are assigned to
      different ligand binding states since key residues are conserved. This suggests
      that the molecular determinants of ligand recognition and reactivity are highly
      conserved across species. We conclude that it would be difficult to target the
      parasite enzyme in preference to the host enzyme and therefore glutathione
      synthetase may not be a suitable target for antiparasitic drug discovery.

PMID- 20045437
TI  - Statin-triggered cell death in primary human lung mesenchymal cells involves p53
      PUMA and release of Smac and Omi but not cytochrome c.
AB  - Statins inhibit 3-hydroxy-3-methyl-glutarylcoenzyme CoA (HMG-CoA) reductase, the
      proximal enzyme for cholesterol biosynthesis. They exhibit pleiotropic effects
      and are linked to health benefits for diseases including cancer and lung disease.
      Understanding their mechanism of action could point to new therapies, thus we
      investigated the response of primary cultured human airway mesenchymal cells,
      which play an effector role in asthma and chronic obstructive lung disease
      (COPD), to simvastatin exposure. Simvastatin induced apoptosis involving caspase
      9, -3 and -7, but not caspase-8 in airway smooth muscle cells and fibroblasts.
      HMG-CoA inhibition did not alter cellular cholesterol content but did abrogate de
      novo cholesterol synthesis. Pro-apoptotic effects were prevented by exogenous
      mevalonate, geranylgeranyl pyrophosphate and farnesyl pyrophosphate, downstream
      products of HMG-CoA. Simvastatin increased expression of Bax, oligomerization of
      Bax and Bak, and expression of BH3-only p53-dependent genes, PUMA and NOXA.
      Inhibition of p53 and silencing of p53 unregulated modulator of apoptosis (PUMA)
      expression partly counteracted simvastatin-induced cell death, suggesting a role
      for p53-independent mechanisms. Simvastatin did not induce mitochondrial release
      of cytochrome c, but did promote release of inhibitor of apoptosis (IAP)
      proteins, Smac and Omi. Simvastatin also inhibited mitochondrial fission with the
      loss of mitochondrial Drp1, an essential component of mitochondrial fission
      machinery. Thus, simvastatin activates novel apoptosis pathways in lung
      mesenchymal cells involving p53, IAP inhibitor release, and disruption of
      mitochondrial fission.

PMID- 20045438
TI  - Adverse experiences in childhood influence brain responses to emotional stimuli
      in adult psychiatric patients.
AB  - Previous results suggest that early life stress (ELS) may be related to altered
      cortical responses to emotional stimuli. In a previous study, we found suppressed
      cortical responses to emotional pictures in psychiatric patients with high-ELS.
      The present study explored the stability of this effect across time and
      stimulation conditions. In addition, the relationship between ELS and current
      life stress was examined, and we probed whether this current life stress was
      related to the cortical responses. Fifteen patients with high, 16 patients with
      low-ELS and 15 psychiatrically healthy subjects with low-ELS participated in two
      sessions 8 months apart. Subjects monitored a rapid serial presentation of
      pleasant, neutral and unpleasant pictures during magnetoencephalographic
      recording. In both sessions, estimated neural activity in occipital-parietal
      temporal regions between 70 and 250 ms after picture onset was smaller in
      patients, particularly in those with high-ELS, compared to healthy subjects.
      Modulation of activity by arousing (pleasant and unpleasant) compared to neutral
      stimuli around 200 ms post-stimulus did not differ between groups, whereas around
      300 ms, patients did not show the pronounced cortical response to pleasant
      stimuli exhibited by healthy subjects. Results suggest that ELS and psychiatric
      disorder (1) diminish early perceptual processing (<200 ms) of emotional stimuli
      without substantially affecting activity modulation by stimulus arousal value,
      (2) diminish later attention allocation processes (>300 ms), and (3) are related
      to more recent life stress. High intraindividual correlations of activity
      patterns between sessions suggest lasting effects of ELS on processing modes.

PMID- 20045439
TI  - Influenza A virus subtypes in wild birds in North-Eastern Spain (Catalonia).
AB  - Since the spread of H5N1 highly pathogenic avian influenza virus in 2005, many
      surveillance programmes have been initiated in poultry and wild birds worldwide.
      This study describes for the first time the detection of different subtypes of
      avian influenza viruses (AIV) in wild birds in the West Mediterranean area
      (Catalonia, North-Eastern Spain). During a 3-year period (from mid-2006 to mid
      2009), 1374 birds from 16 different families were examined, and a total of 62 AIV
      were detected by means of a real-time reverse transcriptase PCR assay. AIV were
      more frequently detected in Anatidae, Phoenicopteridae, Rallidae and Laridae
      families. Of the 62 positive samples, 28 AIV could be isolated in embryonated
      eggs. All isolates were subtyped by haemagglutinin and neuraminidase inhibition
      techniques and 10 different haemagglutinins (HA) and 7 neuraminidases (NA) were
      found in 13 different subtype combinations. The most common combinations were
      H4N6 (22.2%) and H1N1 (18.5%). The HA and NA gene sequences of different AIV
      subtypes were compared and aligned with those available AIV strains from genome
      databases. Our studies on AIV phylogenetic analysis revealed that all AIV genes
      sequenced from wild birds in North-Eastern Spain clustered within Eurasian avian
      clades, including the sequences of H8, N4 and N5 genes analyzed for the first
      time in Europe. The results contribute to the understanding of AIV in the
      Mediterranean area and in Europe.

PMID- 20045440
TI  - IL-17A suppresses the expression of bone resorption-related proteinases and
      osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells.
AB  - Interleukin-17 (IL-17) is produced exclusively by activated T cells and
      neutrophils, and stimulates osteoclastic bone resorption via osteoblasts by
      inducing the expression of "receptor activator of NF-kappaB (RANK) ligand"
      (RANKL). However, the direct effects of IL-17 on the differentiation of
      osteoclast precursors into osteoclasts and on the function of osteoclasts have
      not been clarified. Therefore, we examined the effects of IL-17A on the
      differentiation of osteoclast precursors using RAW264.7 cells and also on the
      expression of carbonic anhydrase II (CA II), cathepsin K, matrix
      metalloproteinases-9 (MMP-9), RANK, c-fms, and IL-17 receptors in these cells.
      The cells were cultured with or without 0.1, 1.0, 10 or 50 ng/mL IL-17 in the
      presence of soluble RANKL for up to 10 days. The CA II, cathepsin K, and MMP-9
      mRNA and protein expression levels were examined using real-time PCR and Western
      blotting, respectively. The mRNA expression levels of RANK, c-fms, and IL-17
      receptors were monitored by real-time PCR. Osteoclast differentiation was
      estimated using tartrate-resistant acid phosphatase (TRAP) staining of the cells.
      TRAP-positive cells were observed after day 5 of culture, and the number of cells
      decreased in the presence of 10 and 50 ng/mL IL-17A at days 5 and 7. In the
      presence of IL-17A, the expressions of cathepsin K, MMP-9 and c-fms decreased
      markedly on days 5 and/or 7 of culture, whereas the expression of CA II and IL-17
      receptor (type A) increased remarkably at days 3 and 7, respectively. The
      expression of RANK and IL-17 receptor (type C) was not affected by the addition
      of IL-17A. These results suggest that the differentiation of osteoclast
      precursors into osteoclasts is suppressed at high concentrations of IL-17A.
      Furthermore, IL-17A suppresses the hydrolysis of matrix proteins during bone
      resorption by decreasing the production of cathepsin K and MMP-9 in osteoclasts.

PMID- 20045441
TI  - Mechanisms of triplex DNA-mediated inhibition of transcription initiation in
      cells.
AB  - Triplex-forming oligonucleotides (TFOs) are attractive tools to control gene
      expression at the transcriptional level. This anti-gene approach has proven to be
      successful in various experimental settings. However, the mechanisms leading to
      transcriptional repression in cells have not been fully investigated yet. Here,
      we examined the consequence of triplex DNA formation on the binding of
      transcriptional activators, co-activators and RNA Polymerase II to the ets2 gene
      promoter using chromatin immunoprecipitation assays. The triplex target sequence
      was located approximately 40-bp upstream of the transcription start site (TSS)
      and overlapped an Sp1 binding site relevant for ets2 transcription. We found that
      the ets2-TFO prevented binding of Sp1, TAF(II)130 and TAF(II)250 to the ets2
      promoter, while binding of RNA polymerase II and TBP were not affected. The
      effects were both sequence and target specific, since the TFO had no effect on
      the c-myc promoter and a mutated ets2 promoter construct. Thus, triplex DNA
      formation near a TSS leads to formation of a non-functional pre-initiation
      complex (PIC) by blocking binding of transcriptional activators and co-activator
      molecules. This is the first direct demonstration of interference with PIC
      assembly at the TSS by oligonucleotide-triplex DNA formation in cells.

PMID- 20045442
TI  - Eriocalyxin B induces apoptosis in lymphoma cells through multiple cellular
      signaling pathways.
AB  - OBJECTIVE: Eriocalyxin B (EriB) is a natural diterpenoid purified from Isodon
      eriocalyx var. laxiflora and possesses strong antileukemic activity. In this
      study, we further investigated its effect and mechanism of action in human
      lymphoma. MATERIALS AND METHODS: In vitro, a series of B- and T-lymphoma cells
      were treated with EriB. Cell apoptosis was analyzed using flow cytometric assay.
      Expression of proteins related to apoptosis and cell signal transduction were
      assessed using Western blot. In vivo antitumor activity of EriB was examined in
      murine xenograft B- and T-lymphoma models, with in situ cell apoptosis detected
      by terminal deoxytransferase-catalyzed DNA nick-end labeling assay. RESULTS: EriB
      significantly inhibited lymphoma cell proliferation and induced apoptosis in
      association with caspase activation. Antiapoptotic Bcl-2 family members Bcl-2 and
      Bcl-xL were downregulated, with proapoptotic member Bax stable or upregulated,
      resulting in reduced Bcl-2/Bax and Bcl-xL/Bax ratios. Meanwhile, multiple signal
      transduction pathways were involved in lymphoma cell apoptosis in response to
      EriB, including inhibition of nuclear factor (NF)-kappaB and AKT pathways, and
      the activation of extracellular signal-related kinase (ERK) pathway. AKT
      inactivation was related to increased expression of cyclin-dependent kinase
      inhibitor P21, decreased expression of antiapoptotic phosphorylated form of Bad,
      and NF-kappaB activator IkappaB kinase alpha/beta. ERK activation corresponded to
      reactive oxygen species production and could be blocked by antioxidant
      dithiothreitol. In murine xenograft lymphoma models, EriB remarkably inhibited
      tumor growth and induced in situ tumor cell apoptosis. CONCLUSION: These findings
      broaden the value of EriB as a promising candidate targeting apoptosis cascade in
      treatment of hematological malignancies.

PMID- 20045443
TI  - Auto-reconstitution of the T-cell compartment by radioresistant hematopoietic
      cells following lethal irradiation and bone marrow transplantation.
AB  - OBJECTIVE: In lethally irradiated bone marrow chimeras, part of the reconstituted
      T-cell compartment is derived from the irradiated host, but the detailed origin
      and functional activity of host-derived T cells has not been thoroughly analyzed.
      Herein, we determine the origin and function of radioresistant host-derived T
      cells. MATERIALS AND METHODS: Lethally irradiated thymectomized or
      nonthymectomized C57BL/6 host mice were reconstituted with syngeneic bone marrow,
      itself incapable of generating T cells. Using fetal thymic organ cultures, bulk
      and limiting dilution assays on OP9-DL1 stromal cells, unambiguous cohorts of
      thymus-derived and peripheral T-cell-derived T cells were phenotypically
      characterized by flow cytometry and functionally characterized by their ability
      to participate in a T-cell-dependent antibody response. RESULTS: Both thymus
      derived and peripheral T-cell-derived host T cells are functional and can
      reconstitute 35% of the normal T-cell pool. By comparing thymectomized vs
      nonthymectomized hosts, host-derived T cells were shown to comprise a major (70%)
      subpopulation of de novo generated, thymus-derived, polyclonal, naive cells, and
      a minor subpopulation of surviving, peripheral, oligoclonal, memory-like cells.
      Unlike euthymic recipients, mice whose T cells were derived from surviving
      peripheral T cells were frequently incapable of mounting a T-cell-dependent
      antibody response. Host-derived thymocytes regenerated in an interleukin-7
      dependent fashion from conventional DN2 thymocytes and their differentiation
      recapitulated normal thymic ontogeny. CONCLUSION: We characterized, for the first
      time, functional radioresistant DN2-phenotype thymic T-cell precursors, the T
      cell progeny of which might provide a first line of defense against infections
      during the lymphopenic phase post-bone marrow transplantation.

PMID- 20045444
TI  - An evolutionary approach for gene selection and classification of microarray data
      based on SVM error-bound theories.
AB  - Microarrays have thousands to tens-of-thousands of gene features, but only a few
      hundred patient samples are available. The fundamental problem in microarray data
      analysis is identifying genes whose disruption causes congenital or acquired
      disease in humans. In this paper, we propose a new evolutionary method that can
      efficiently select a subset of potentially informative genes for support vector
      machine (SVM) classifiers. The proposed evolutionary method uses SVM with a given
      subset of gene features to evaluate the fitness function, and new subsets of
      features are selected based on the estimates of generalization error of SVMs and
      frequency of occurrence of the features in the evolutionary approach. Thus, in
      theory, selected genes reflect to some extent the generalization performance of
      SVM classifiers. We compare our proposed method with several existing methods and
      find that the proposed method can obtain better classification accuracy with a
      smaller number of selected genes than the existing methods.

PMID- 20045446
TI  - Short term treatment with estradiol decreases the rate of newly generated cells
      in the subventricular zone and main olfactory bulb of adult female mice.
AB  - Adult neurogenesis occurs most notably in the subgranular zone (SGZ) of the
      hippocampal dentate gyrus and in the olfactory bulb (OB) where new neurons are
      generated from neural progenitors cells produced in the subventricular zone (SVZ)
      of the forebrain. As it is well known that gonadal steroid hormones, primarily
      estradiol, modulate neurogenesis in the hippocampus of adult female rodents, we
      wanted to determine whether estradiol would also affect the proliferation of
      progenitor cells in the SVZ and by consequence the rate of newly generated cells
      in the main OB. Thus a first group of adult female C57Bl6/J mice was
      ovariectomized and received a short term treatment with estradiol (single
      injection of 1 or 10 microg 17beta-estradiol or Silastic capsule of estradiol
      during 2 days) before receiving a single injection with BrdU to determine whether
      estradiol would modulate the cell proliferation in the SVZ. A second group of
      adult ovariectomized female mice was submitted to the same estradiol treatment
      before receiving four BrdU injections, and was sacrificed 21 days later to
      determine whether a modulation in cell proliferation actually leads to a
      modulation in the number of newborn cells in the main OB. We observed a decrease
      in cell proliferation in the SVZ following either dose of estradiol compared to
      the controls. Furthermore, 21 days after their generation in the SVZ, the number
      of BrdU labeled cells was also lower in the main OB, both in the granular and
      periglomerular cell layers of estradiol-treated animals. These results show that
      a short term treatment with estradiol actually downregulates cell proliferation
      leading to a decreased number of newborn cells in the OB.

PMID- 20045445
TI  - A comprehensive analysis of the effect of DSP4 on the locus coeruleus
      noradrenergic system in the rat.
AB  - Degeneration of the noradrenergic neurons in the locus coeruleus (LC) is a major
      component of Alzheimer's (AD) and Parkinson's disease (PD), but the consequence
      of noradrenergic neuronal loss has different effects on the surviving neurons in
      the two disorders. Therefore, understanding the consequence of noradrenergic
      neuronal loss is important in determining the role of this neurotransmitter in
      these neurodegenerative disorders. The goal of the study was to determine if the
      neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) could be used as a
      model for either (or both) AD or PD. Rats were administered DSP4 and sacrificed 3
      days 2 weeks and 3 months later. DSP4-treatment resulted in a rapid, though
      transient reduction in norepinephrine (NE) and NE transporter (NET) in many brain
      regions receiving variable innervation from the LC. Alpha(1)-adrenoreceptors
      binding site concentrations were unchanged in all brain regions at all three time
      points. However, an increase in alpha(2)-AR was observed in many different brain
      regions 2 weeks and 3 months after DSP4. These changes observed in forebrain
      regions occurred without a loss in LC noradrenergic neurons. Expression of
      synthesizing enzymes or NET did not change in amount of expression/neuron despite
      the reduction in NE tissue content and NET binding site concentrations at early
      time points, suggesting no compensatory response. In addition, DSP4 did not
      affect basal activity of LC at any time point in anesthetized animals, but 2
      weeks after DSP4 there is a significant increase in irregular firing of
      noradrenergic neurons. These data indicate that DSP4 is not a selective LC
      noradrenergic neurotoxin, but does affect noradrenergic neuron terminals locally,
      as evident by the changes in transmitter and markers at terminal regions.
      However, since DSP4 did not result in a loss of noradrenergic neurons, it is not
      considered an adequate model for noradrenergic neuronal loss observed in AD and
      PD.

PMID- 20045447
TI  - Mu and kappa opioid receptor expression in the mediobasal hypothalamus and
      effectiveness of selective antagonists on prolactin release during lactation.
AB  - Endogenous opioid peptides are involved in prolactin release during lactation, in
      part by decreasing tuberoinfundibular dopaminergic (TIDA) neuronal activity. Both
      mu (mu) and kappa (kappa) opioid receptors have a role in the suckling-induced
      prolactin rise after 4-5 h up deprivation. The aim of this study was to
      investigate effects of mu opioid receptor antagonist, beta-funaltrexamine (beta
      FNA), and kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on
      prolactin secretion and TIDA neuronal activity in lactating rats after 18 h pup
      deprivation. After 4 h separation from pups, the suckling-induced prolactin rise
      was abolished by 16 microg nor-BNI and 5 microg beta-FNA, coincident with
      increased dihydroxyphenylacetic acid (DOPAC):dopamine ratio in the stalk-median
      eminence (SME). However, after 18 h pups separation, these same doses of nor-BNI
      and beta-FNA did not alter the prolactin surge or DOPAC:dopamine ratios in the
      SME. Higher doses of nor-BNI (32 microg) and beta-FNA (10 microg) were required
      to inhibit suckling-induced prolactin secretion. beta-FNA (10 microg) increased
      the DOPAC:dopamine ratio in the SME, whereas nor-BNI (32 microg) treatment had no
      effect. The mu and kappa opioid receptor mRNA levels in the mediobasal
      hypothalamus were similar to suckled control rats after 4 h pup deprivation, but
      increased 1.4-fold after 18 h pup deprivation. These data support involvement of
      endogenous opioidergic systems in the suckling-induced prolactin rise after a
      prolonged (18 h) period of pup deprivation, as well as the shorter (4 h) pup
      deprivation period previously reported. Suppression of TIDA neuronal activity
      likely played a part in mu opioid receptor input to the suckling-induced
      prolactin rise after both 4 h and 18 h separation, whereas non-dopaminergic input
      was implicated with kappa opioid receptors after 18 h pup deprivation. Increased
      mu and kappa opioid receptors gene expression in the mediobasal hypothalamus may
      contribute to reduced effectiveness of opioid receptor antagonists to block
      suckling-induced prolactin release after 18 h pup deprivation.

PMID- 20045448
TI  - Methamphetamine acts on subpopulations of neurons regulating sexual behavior in
      male rats.
AB  - Methamphetamine (Meth) is a highly addictive stimulant. Meth abuse is commonly
      associated with the practice of sexual risk behavior and increased prevalence of
      Human Immunodeficiency Virus and Meth users report heightened sexual desire,
      arousal, and sexual pleasure. The biological basis for this drug-sex nexus is
      unknown. The current study demonstrates that Meth administration in male rats
      activates neurons in brain regions of the mesolimbic system that are involved in
      the regulation of sexual behavior. Specifically, Meth and mating co-activate
      cells in the nucleus accumbens core and shell, basolateral amygdala, and anterior
      cingulate cortex. These findings illustrate that in contrast to current belief
      drugs of abuse can activate the same cells as a natural reinforcer, that is
      sexual behavior, and in turn may influence compulsive seeking of this natural
      reward.

PMID- 20045449
TI  - Enhanced vulnerability of PARK6 patient skin fibroblasts to apoptosis induced by
      proteasomal stress.
AB  - Proteasomal dysfunction and apoptosis are major hallmarks in the pathophysiology
      of Parkinson's disease (PD). PARK6 which is caused by mutations in the
      mitochondrial protein kinase PINK1 is a rare autosomal-recessively inherited
      disorder mimicking the clinical picture of PD. To investigate the cytoprotective
      physiological function of PINK1, we used primary fibroblasts from three patients
      homozygous for G309D-PINK1 as well as SHEP neuroblastoma cells stably
      overexpressing GFP-tagged wild type (wt) PINK1. Here we demonstrate that
      overexpression of wt PINK1 inhibits activation of Bax and release of cytochrome
      c, thereby diminishing caspase 9 processing and effector caspase activity after
      induction of proteasomal stress with the proteasome inhibitor (PI) MG132 in SHEP
      cells. Conversely, effector caspase activation induced by PIs, but not by the
      unrelated apoptotic stimulus staurosporine was potently enhanced in primary
      fibroblasts from homozygous PARK6 patients in comparison to those of heterozygous
      carriers or unaffected siblings. SHEP cells overexpressing wt PINK1 showed an
      elevated expression of the cytoprotective gene parkin, whereas PARK6 fibroblasts
      displayed significantly decreased expression of parkin in comparison to wild type
      control cells. Interestingly, overexpressed GFP-PINK1 was exclusively localized
      in the mitochondria of SHEP cells, but was redistributed to the cytoplasm under
      conditions of proteasomal stress. Our data indicate that PINK1 plays an important
      and specific physiological role in protecting cells from proteasomal stress, and
      suggest that PINK1 might exert its cytoprotective effects upstream of
      mitochondria engagement.

PMID- 20045450
TI  - Matrix metalloproteinase-dependent shedding of intercellular adhesion molecule-5
      occurs with long-term potentiation.
AB  - Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases
      that can be released or activated in a neuronal activity dependent manner.
      Although pathologically elevated levels of MMPs may be synaptotoxic,
      physiologically appropriate levels of MMPs may instead enhance synaptic
      transmission. MMP inhibitors can block long term potentiation (LTP), and at least
      one family member can affect an increase in the volume of dendritic spines. While
      the mechanism by which MMPs affect these changes is not completely understood,
      one possibility is that the cleavage of specific synaptic cell adhesion molecules
      plays a role. In the present study, we have examined the ability of neuronal
      activity to stimulate rapid MMP dependent shedding of the intercellular adhesion
      molecule-5 (ICAM-5), a synaptic adhesion molecule that is thought to inhibit the
      maturation and enlargement of dendritic spines. Since such cleavage would likely
      occur within minutes if it were relevant to a process such as LTP, we focused on
      post stimulus time points of 30 min or less. We show that NMDA can stimulate
      rapid shedding of ICAM-5 from cortical neurons in dissociated cell cultures and
      that such shedding is diminished by pretreatment of cultures with inhibitors that
      target MMP-3 and -9, proteases thought to influence synaptic plasticity.
      Additional studies suggest that MMP mediated cleavage of ICAM-5 occurs at amino
      acid 780, so that the major portion of the ectodomain is released. Since
      reductions in ICAM-5 have been linked to changes in dendritic spine morphology
      that are associated with LTP, we also examined the possibility that MMP dependent
      ICAM-5 shedding occurs following high frequency tetanic stimulation of murine
      hippocampal slices. Results show that the shedding of ICAM-5 occurs in
      association with LTP, and that both LTP and the associated ICAM-5 shedding are
      reduced when slices are pretreated with an MMP inhibitor. Together, these
      findings suggest that neuronal activity is linked to the shedding of a molecule
      that may inhibit dendritic spine enlargement and that MMPs can affect this
      change. While further studies will be necessary to determine the extent to which
      cleavage of ICAM-5 in particular contributes to MMP dependent LTP, our data
      support an emerging body of literature suggesting that MMPs are critical
      mediators of synaptic plasticity.

PMID- 20045451
TI  - Mastication overload causes an increase in O2- production into the subnucleus
      oralis of the spinal trigeminal nucleus.
AB  - The aim of the present study was to evaluate the production of superoxide anion
      (O(2)(-)) in the trigeminal complex nuclei after a functional mechanical overload
      of the teeth due to the preference for masticating on one side in rats. The
      preference for masticating on one side was induced by the discomfort due to a
      small abrasion of one molar; such lateralisation in mastication was confirmed by
      electromyography. The production of O(2)(-) was evaluated in the trigeminal
      nuclei by fluorescence microscopy after an injection of dihydroethidium. The
      results showed that there was an increased production of O(2)(-) in the
      subnucleus oralis of the spinal trigeminal nucleus in the same side where the
      mastication was preferred. This result demonstrates that an increased activity of
      non-painful sensory neurons can enhance the production of reactive oxygen species
      within the central second order sensory nuclei.

PMID- 20045452
TI  - The in vitro and in vivo anti-tumor effect of layered double hydroxides
      nanoparticles as delivery for podophyllotoxin.
AB  - In this research, we intercalated anti-tumor drug podophyllotoxin (PPT) into
      layered double hydroxides (LDHs) and investigated the in vitro cytotoxicity to
      tumor cells, the cellular uptake and in vivo anti-tumor inhibition of PPT-LDH.
      The nanohybrids were prepared by a two-step method with the size of 80-90nm and
      the zeta potential of 20.3mV. The in vitro cytotoxicity experiment indicated that
      PPT-LDH nanoparticles show better anti-tumor efficacy than PPT and are more
      readily taken up by Hela cells. PPT-LDH shows a long-term suppression effect on
      the tumor growth, and enhances the apoptotic process of tumor cells. The in vivo
      tests reveal that delivery of PPT via LDH nanoparticles is more efficient, but
      the mice toxicity of PPT in PPT-LDH hybrids is reduced in comparison with PPT
      alone. Pharmacokinetics study displays a prolonged circulation time and an
      increased bioavailability of PPT-LDH than PPT. These observations imply that LDH
      nanoparticles are the potential carrier of anti-tumor drugs in a range of new
      therapeutic applications.

PMID- 20045453
TI  - Cytotoxic activity of 9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol from
      Eulophia nuda against human cancer cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eulophia nuda L. (Orchidaceae) is a medicinally
      important terrestrial orchid used for the treatment of tumours and various health
      problems by the local healers throughout the Western Ghats region in Maharashtra
      (India). AIM OF THE STUDY: To isolate the active molecule from Eulophia nuda and
      to study its cytotoxic potential against human cancer cells. MATERIALS AND
      METHODS: The crude methanolic extract of Eulophia nuda tubers was fractionated by
      stepwise gradient of the solvents-chloroform-methanol to isolate the pure
      compound. Isolated pure compound was assessed for its cytotoxic potential against
      human breast cancer cell lines, MCF-7 and MDA-MB-231 using MTT assay. Structure
      elucidation of the isolated active compound was carried out by extensive
      spectroscopic analysis including (1)H NMR, (13)C NMR, NOESY, COSY, LC-MS and IR.
      RESULTS: The isolated active molecule was identified as phenanthrene derivative
      9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol. This compound showed good
      antiproliferative activity against human breast cancer cell lines MCF-7 (91%) and
      MDA-MB-231 (85%) at 1000 microg/ml concentration. CONCLUSION: 9,10-Dihydro-2,5
      dimethoxyphenanthrene-1,7-diol from Eulophia nuda tubers showed good growth
      suppressive effect against human cancer cell lines MCF-7 and MDA-MB-231 making it
      a potential biomolecule against human cancer.

PMID- 20045454
TI  - Lagerstroemia speciosa extract inhibit TNF-induced activation of nuclear factor
      kappaB in rat cardiomyocyte H9c2 cells.
AB  - AIM OF THE STUDY: Lagerstroemia speciosa has been used as a folk medicine among
      people with diabetes in the Philippines. It is known to exhibit antidiabetic,
      antiobesity, and glucose transport activities through mechanisms not well
      defined. Diabetes leads to cardiomyocyte hypertrophy in association with an
      upregulation of vasoactive factors and activation of nuclear factor (NF)-kappaB
      and activating protein-1. We therefore investigated the effect of Lagerstroemia
      speciosa on the activation of NF-kappaB as a key mediator of cardiomyocyte
      hypertrophy, in rat cardiomyocyte H9c2 cells. MATERIALS AND METHODS: Water
      extract of Lagerstroemia speciosa (Lythraceae family) was prepared. H9c2 cells
      were used for treatment of Lagerstroemia speciosa extract with/without tumor
      necrosis factor (TNF). To examine NF-kappaB's activation, we performed an
      electrophoretic mobility shift assay (EMSA). RESULTS: The activation of NF-kappaB
      by TNF was completely blocked by a Lagerstroemia speciosa extract in a dose- and
      time-dependent manner in H9c2 cells. CONCLUSION: Overall, our results indicate
      that Lagerstroemia speciosa can inhibit DNA-binding of NF-kappaB. This may
      explain its possible inhibition of diabetes-induced cardiomyocyte hypertrophy.

PMID- 20045455
TI  - Growth arrest and induction of apoptotic and non-apoptotic programmed cell death
      by, Physalis minima L. chloroform extract in human ovarian carcinoma Caov-3
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the whole plant of Physalis
      minima L. is traditionally consumed to treat cancer. Its anticancer property has
      been previously verified (using in vitro cytotoxicity assays) against NCI-H23
      lung, CORL23 lung and MCF7 breast cancer cell lines but the mechanism underlying
      the anticancer potency towards ovarian carcinoma cells remain unclear. AIM OF THE
      STUDY: The present study is aimed to systematically determine the cytotoxicity
      and possible cell death mechanism elicited by the chloroform extract of Physalis
      minima in human ovarian Caov-3 carcinoma. MATERIALS AND METHODS: Cytotoxicity of
      the extract was measured using the methylene blue assay. The mechanism of cell
      death was determined using four independent methods, namely DeadEnd assay to
      label the DNA fragmentation nuclei cells, RT-PCR analysis to determine the mRNA
      expression level of three apoptotic genes (c-myc, p53 and caspase-3 genes),
      Transmission Electron Microscope (TEM) analysis to describe the ultra structural
      characteristics and annexin V and propidium iodide staining to confirm the types
      and stages of cell deaths. RESULTS: Cytotoxicity screening of the extract on Caov
      3 cells exhibited concentration- and time-dependent inhibitory effects. A
      combination of apoptotic and autophagic programmed cell death was detected. The
      apoptotic characteristic was initially determined by DNA fragmentation followed
      by the expression of c-myc and p53 genes that was much earlier than caspase-3.
      Apoptotic ultra structural changes (including clumping and magination of
      chromatin, blebbing and convolution of nucleus membrane and formation of
      apoptotic bodies) and autophagy (Type II non-apoptotic programmed cell death)
      with distinct vacuolated morphology were detected in TEM analysis. The existence
      of these programmed cell deaths was then corroborated using annexin V and
      propidium iodide staining. CONCLUSIONS: The chloroform extract of Physalis minima
      exerted anticancer effect due to a combination of apoptotic and autophagic cell
      death mechanisms on Caov-3 cells. The induction of these programmed cell deaths
      was mediated via c-myc, p53 and caspase-3 dependent pathway. The results could
      provide a valuable insight in cancer therapy.

PMID- 20045456
TI  - Anti-inflammatory activity of roots of Ecbolium viride (Forsk) Merrill.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally the aqueous extracts of dried roots
      of the plant Ecbolium viride are used for menorrhagia, rheumatism and jaundice.
      AIM OF THE STUDY: The aim was to evaluate the anti-inflammatory activity of
      Ecbolium viride extract in an in vivo model. MATERIALS AND METHODS: The ethyl
      acetate fraction of Ecbolium viride root extract was prepared and administered
      orally to rats. The anti-inflammatory activity of Ecbolium viride was determined
      by carrageenan-induced paw edema and cotton pellet granuloma models. RESULTS:
      Oral administration of Ecbolium viride extract reduced inflammation significantly
      (P<0.01) in both the carageenan paw edema and the cotton pellet granuloma models.
      CONCLUSIONS: The results of the study supported the traditional use of Ecbolium
      viride in the treatment for inflammatory disease.

PMID- 20045457
TI  - Photoperiod modulates gut bacteria composition in male Siberian hamsters
      (Phodopus sungorus).
AB  - Seasonal changes in day length (i.e., photoperiod) provide animals with a
      reliable environmental cue to determine time of year, and many physiological
      changes occur in laboratory animals simply by extending or shortening day length.
      Male Siberian hamsters (Phodopus sungorus) housed in long summer-like day lengths
      have significantly elevated body and fat masses compared to short-day hamsters.
      Because others have demonstrated that the intestinal microbiota of humans and
      rodents promotes host adiposity, we hypothesized that photoperiod-induced changes
      in body and fat masses could be associated with changes in the microbial
      composition in the intestines. We used bacterial tag-encoded FLX amplicon
      pyrosequencing (bTEFAP) to assess microbial diversity in the cecal contents of
      hamsters; long days significantly increased the relative abundance of bacteria in
      the phylum Proteobacteria. This effect was primarily due to a significant
      increase in the abundance of the genus Citrobacter, with both the abundance of
      Proteobacteria and Citrobacter spp. significantly correlated with body mass and
      with inguinal fat mass. In general, the abundance of the Firmicutes phylum was
      inversely associated with body mass. These data indicate that the intestinal
      microbiota are responsive to changes in photoperiod and suggest that these
      changes may in part influence photoperiodic changes in body and fat masses.

PMID- 20045458
TI  - Cyclic AMP negatively regulates prodigiosin production by Serratia marcescens.
AB  - Many Serratia marcescens strains produce the red pigment prodigiosin, which has
      antimicrobial and anti-tumor properties. Previous reports suggest that cyclic AMP
      (cAMP) is a positive regulator of prodigiosin production. Supporting this model,
      the addition of glucose to growth medium inhibited pigment production in rich and
      minimal media. Unexpectedly, we observed highly elevated levels of prodigiosin
      production in isogenic strains with mutations in genes involved in cAMP
      production (cyaA and crr) and in cAMP-dependent transcriptional signaling (crp).
      Multicopy expression of the Escherichia coli cAMP-phosphodiesterase gene, cpdA,
      also conferred a striking increase in prodigiosin production. Exogenous cAMP
      decreased both pigment production and pigA-lacZ transcription in the wild-type
      (WT) strain, and pigA-lacZ transcription was significantly increased in a crp
      mutant relative to WT. Suppressor and epistasis analysis indicate that the
      hyperpigment phenotype was dependent upon pigment biosynthetic genes (pigA, pigB,
      pigC, pigD and pigM). These experiments establish cAMP as a negative regulator of
      prodigiosin production in S. marcescens.

PMID- 20045459
TI  - Human steroidogenic factor-1 (hSF-1) regulates progesterone biosynthesis and
      growth of ovarian surface epithelial cancer cells.
AB  - The majority of cancers derived from ovarian surface epithelial (OSE) cells are
      lethal. Estrogens promote proliferation of OSE cells, whereas progesterone
      inhibits proliferation and promotes apoptosis of OSE cells. Human steroidogenic
      factor-1 (hSF-1) induction of the steroidogenic acute regulatory protein (StAR)
      gene, and the steroidogenic enzymes CYP11A1 and HSD3B2 is central to progesterone
      biosynthesis. Whereas hSF-1 and StAR are expressed in human ovarian surface
      epithelial (HOSE) cells, hSF-1 and StAR protein were not expressed in a panel of
      malignant ovarian cancer cell lines (SKOV-3, BG-1, and Caov-3), and in human OSE
      cells immortalized by SV40 large T antigen (IOSE-121). Transient expression of
      hSF-1 in SKOV-3 cells activated the expression of StAR, p450scc and 3betaHSD-II
      mRNAs, and induced progesterone biosynthesis. Additionally, hSF-1 suppressed
      proliferation and promoted apoptosis of SKOV-3 cells and suppressed SKOV-3 cell
      growth induced by ERalpha and estradiol. These findings suggest that hSF-1 is
      central to progesterone biosynthesis in OSE cells. Human SF-1 may decrease OSE
      cancer cell numbers directly by apoptosis, and indirectly by opposing estradiol
      induced proliferation. These findings are consistent with the hypothesis, that
      down-regulation of hSF-1 contributes to progression of ovarian epithelial
      cancers.

PMID- 20045460
TI  - Preventive effects of syngeneic bone marrow transplantation on diabetic
      nephropathy in mice.
AB  - Treatment with autologous bone marrow transplantation (ABMT) can change the
      natural history of diabetes in patients with new-onset Type 1 diabetes (T1D).
      Effects of syngeneic bone marrow transplantation (syn-BMT) on diabetic
      nephropathy were studied in streptozotocin-induced diabetic mice. Diabetic mice
      received sibling's bone marrow on days 3, 10, 20, or 40 after T1D onset,
      respectively. Renal pathology, levels of oxidative stress, and the expressions of
      angiotensinogen (AGT), monocyte chemoattractant protein-1 (MCP-1) and
      transforming growth factor beta 1 (Tgf-beta1) mRNA were investigated. Treatment
      with syn-BMT when disease was early-onset reduced mesangial area expansion and
      kidney enlargement; besides, if it is given on day 10, syn-BMT attenuated
      glomerular hypertrophy. Oxidative stress factors such as catalase (CAT) and
      superoxide radical anion O(2-) (O(2-)) were markedly maintained by syn-BMT
      compared to mice without treatment. In diabetic mice without treatment, renal AGT
      and MCP-1 mRNA were increased, while they were effectively suppressed by syn-BMT.
      But it showed no changes or even increment in Tgf-beta1 mRNA after syn-BMT. Syn
      BMT, if applied when disease was early-onset, ameliorated diabetic renal injury.
      These preventive effects could be partly via maintaining oxidative stress and
      expression of AGT and MCP-1 in kidney in streptozotocin-diabetic mice.

PMID- 20045462
TI  - Human absorption of a supplement containing purified hydroxytyrosol, a natural
      antioxidant from olive oil, and evidence for its transient association with low
      density lipoproteins.
AB  - There is growing interest in the health effects of olive oil polyphenols,
      particularly hydroxytyrosol (HT), for their potential application in the
      treatment of inflammatory conditions such as cardiovascular disease (CVD). As
      oxidative modification of low-density lipoproteins (LDL) plays a central role in
      the development of CVD, natural antioxidants are a main target for the
      nutraceutical industry. In this study we firstly investigated the absorption of
      pure hydroxytyrosol (99.5%) administered as a supplement in an aqueous solution
      (2.5mg/kg BW) in the plasma and urine of healthy volunteers (n=10). Plasma C(max)
      for HT and homovanillic alcohol (HvOH) were detected at 13.0+/-1.5 and 16.7+/
      2.4min, respectively. The HT and HvOH levels were undetectable 2-h after the
      administration. HT, HvOH, homovanillic acid and 3,4-dihydroxyphenylacetic acid
      were found as free forms (44%) or as glucuronide (34.4%) or sulphate (21.2%)
      conjugates in the 24-h urine samples of the subjects. In a second phase of the
      study, the same amounts of HT were administered to the subjects and the presence
      of HT in purified plasma lipoproteins was investigated in LDL fractions freshly
      isolated. 10min after the ingestion of the HT supplement, more than 50% of the
      total amount detected was present in the LDL-purified fractions and its
      concentration declined in accordance with its presence in plasma but no changes
      were found in total antioxidant capacity, malondialdehyde or LDL lag time. These
      results indicate that pure HT transiently associates with LDL lipoproteins in
      vivo.

PMID- 20045461
TI  - Chronic benzylamine administration in the drinking water improves glucose
      tolerance, reduces body weight gain and circulating cholesterol in high-fat diet
      fed mice.
AB  - Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in
      traditional medicine. In mammals, benzylamine is metabolized by semicarbazide
      sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter
      product has insulin-mimicking action, and is involved in the effects of
      benzylamine on human adipocytes: stimulation of glucose transport and inhibition
      of lipolysis. This study examined whether chronic, oral administration of
      benzylamine could improve glucose tolerance and the circulating lipid profile
      without increasing oxidative stress in overweight and pre-diabetic mice. The
      benzylamine diffusion across the intestine was verified using everted gut sacs.
      Then, glucose handling and metabolic markers were measured in mice rendered
      insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine
      in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice
      showed lower body weight gain, fasting blood glucose, total plasma cholesterol
      and hyperglycaemic response to glucose load when compared to HFD control. In
      adipocytes, insulin-induced activation of glucose transport and inhibition of
      lipolysis remained unchanged. In aorta, benzylamine treatment partially restored
      the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers
      were reduced. Resistin and uric acid, surrogate plasma markers of metabolic
      syndrome, were decreased. In spite of the putative deleterious nature of the
      hydrogen peroxide generated during amine oxidation, and in agreement with its in
      vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine
      could be considered as a potential oral agent to treat metabolic syndrome.

PMID- 20045463
TI  - KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation.
AB  - Voltage-gated potassium (Kv) channels play important roles in regulating the
      excitability of myocytes and neurons. Kv4.2 is the primary alpha-subunit of the
      channel that produces the A-type K(+) current in CA1 pyramidal neurons of the
      hippocampus, which is critically involved in the regulation of dendritic
      excitability and plasticity. K(+) channel-interacting proteins, KChIPs (KChIP1
      4), associate with the N-terminal of Kv4.2 and modulate the channel's biophysical
      properties, turnover rate and surface expression. In the present study, we
      investigated the role of Kv4.2 C-terminal PKA phosphorylation site S552 in the
      KChIP4a-mediated effects on Kv4.2 channel trafficking. We found that while
      interaction between Kv4.2 and KChIP4a does not require PKA phosphorylation of
      Kv4.2(S552), phosphorylation of this site is necessary for both enhanced
      stabilization and membrane expression of Kv4.2 channel complexes produced by
      KChIP4a. Enhanced surface expression and protein stability conferred by co
      expression of Kv4.2 with other KChIP isoforms did not require PKA phosphorylation
      of Kv4.2 S552. Finally, we identify A-kinase anchoring proteins (AKAPs) as Kv4.2
      binding partners, allowing for discrete local PKA signaling. These data
      demonstrate that PKA phosphorylation of Kv4.2 plays an important role in the
      trafficking of Kv4.2 through its specific interaction with KChIP4a.

PMID- 20045464
TI  - Bioinformatic mapping and production of recombinant N-terminal domains of human
      cardiac ryanodine receptor 2.
AB  - We report the domain analysis of the N-terminal region (residues 1-759) of the
      human cardiac ryanodine receptor (RyR2) that encompasses one of the discrete RyR2
      mutation clusters associated with catecholaminergic polymorphic ventricular
      tachycardia (CPVT1) and arrhythmogenic right ventricular dysplasia (ARVD2). Our
      strategy utilizes a bioinformatics approach complemented by protein expression,
      solubility analysis and limited proteolytic digestion. Based on the
      bioinformatics analysis, we designed a series of specific RyR2 N-terminal
      fragments for cloning and overexpression in Escherichia coli. High yields of
      soluble proteins were achieved for fragments RyR2(1-606)xHis(6), RyR2(391
      606)xHis(6), RyR2(409-606)xHis(6), Trx.RyR2(384-606)xHis(6), TrxxRyR2(391
      606)xHis(6) and Trx.RyR2(409-606)xHis(6). The folding of RyR2(1-606)xHis(6) was
      analyzed by circular dichroism spectroscopy resulting in alpha-helix and beta
      sheet content of approximately 23% and approximately 29%, respectively, at
      temperatures up to 35 degrees C, which is in agreement with sequence based
      secondary structure predictions. Tryptic digestion of the largest recombinant
      protein, RyR2(1-606)xHis(6), resulted in the appearance of two specific
      subfragments of approximately 40 and 25 kDa. The 25 kDa fragment exhibited
      greater stability. Hybridization with anti-His(6).Tag antibody indicated that
      RyR2(1-606)xHis(6) is cleaved from the N-terminus and amino acid sequencing of
      the proteolytic fragments revealed that digestion occurred after residues 259 and
      384, respectively.

PMID- 20045465
TI  - Transient expression of an IL-23R extracellular domain Fc fusion protein in CHO
      vs. HEK cells results in improved plasma exposure.
AB  - Transient transfection of mammalian cells in suspension culture has recently
      emerged as a very useful method for production of research-scale quantities of
      recombinant proteins. The most commonly used cell lines for this purpose are
      suspension-adapted HEK and CHO cells. We report here that the plasma exposure in
      mice of an IL-23R extracellular domain Fc fusion protein (IL23R-Fc) differed
      dramatically depending on whether the protein was prepared by transient
      transfection of HEK or CHO cells. Specifically, IL23R-Fc expressed using CHO
      cells had about 30-fold higher in vivo plasma exposure compared to the HEK
      expressed protein. In contrast to their differing plasma exposures, the HEK- and
      CHO-expressed proteins had equivalent in vitro biological activity.
      Characterization of the CHO- and HEK-expressed IL23R-Fc proteins indicated that
      the differences in in vivo plasma exposure between them are due to differential
      glycosylation.

PMID- 20045466
TI  - Dynamics and orientation of a cationic antimicrobial peptide in two membrane
      mimetic systems.
AB  - In order to investigate the functional and structural properties of cationic
      alpha-helical peptides in two different membranes, we studied the 20-residue
      peptide maximin H6 in two membrane-mimetic systems by NMR spectroscopy using
      partially (15)N-labeled peptide and paramagnetic relaxation enhancements. Maximin
      H6, which is found in skin secretions of frogs of the Bombinae family, attacks
      gram-negative bacteria and acts haemolytically. While the peptide spontaneously
      folds into similar structures in both neutral dodecylphosphocholine (DPC) and
      negatively charged sodium dodecyl sulphate (SDS) micelles, its structure is more
      flexible in SDS as shown by (15)N relaxation measurements. In addition, it is
      bound closer to the surface of the micelle and rotated by approximately 70
      degrees around its helix axis in the negatively charged membrane surrogate
      compared to the structure in DPC. This might form the basis for peptide-peptide
      interactions through a GxxxG motif, which could finally lead to membrane
      disruption and, thus, preferential attack of negatively charged microbial cell
      walls.

PMID- 20045467
TI  - The role of salt and shear on the storage and assembly of spider silk proteins.
AB  - Major ampullate silk fibers of orb web-weaving spiders have impressive mechanical
      properties due to the fact that the underlying proteins partially fold into
      helical/amorphous structures, yielding relatively elastic matrices that are
      toughened by anisotropic nanoparticulate inclusions (formed from stacks of beta
      sheets of the same proteins). In vivo the transition from soluble protein to
      solid fibers involves a combination of chemical and mechanical stimuli (such as
      ion exchange, extraction of water and shear forces). Here we elucidate the
      effects of such stimuli on the in vitro aggregation of engineered and
      recombinantly produced major ampullate silk-like proteins (focusing on structure
      function relationships with respect to their primary structures), and discuss
      their relevance to the storage and assembly of spider silk proteins in vivo.

PMID- 20045468
TI  - Characterization of recombinantly produced spider flagelliform silk domains.
AB  - The capture spiral of a spider's orb web is made of flagelliform silk, providing
      high elasticity and an outstanding toughness, perfectly suited for trapping prey.
      Flagelliform silk comprises mainly one single protein (FLAG) with an estimated
      molecular weight of 360kDa. We engineered constructs mimicking distinct domains
      of FLAG (eFLAG) and produced them recombinantly to analyze the structure-function
      relationship of FLAG domains and assembly properties of FLAG. While in solution
      the small carboxy-terminal domain is structured, domains from the repetitive core
      region adopt a conformation typical for intrinsically unstructured proteins. To
      investigate the influence of the respective domains on solubility and assembly,
      we tested the aggregation behaviour of individual domains and domain ensembles in
      presence of conditions known to trigger silk assembly. Both, the length of the
      repetitive core domain as well as the presence of the carboxy-terminal non
      repetitive domain showed impact on eFLAG aggregation.

PMID- 20045469
TI  - Two novel secreted ferritins involved in immune defense of Chinese mitten crab
      Eriocheir sinensis.
AB  - As a principal extracellular iron storage molecule, secreted ferritin plays an
      important role in the iron-withholding strategy of innate immunity. In this
      study, two novel secreted ferritins were identified from Chinese mitten crab
      Eriocheir sinensis (designated as EsFer-1 and EsFer-2) by rapid amplification of
      cDNA ends (RACE) approaches and expressed sequence tag (EST) analysis. The full
      length cDNAs of EsFer-1 and EsFer-2 were of 1278 and 1595 bp, respectively, both
      containing a putative iron response element (IRE) in their 5' UTRs and multiple A
      + U-destabilizing elements (TATT or ATTTA) in their 3' UTRs. The ORFs of these
      two crab ferritin cDNAs were of 639 and 663 bp, respectively, encoding two
      peptides of 212 and 220 amino acid residues each with a signal peptide and
      typical structures of ferritins such as four long alpha-helices, one short alpha
      helix and an L-loop. EsFer-2 exhibited higher similarity with the H-ferritins
      from both invertebrates and vertebrates, while EsFer-1 was closer matched to L
      ferritins. The eight amino acid residues identified as metal binding sites in
      vertebrate H-ferritins were conserved in EsFer-2 (Glu53, Tyr60, Glu87, Glu88,
      His91, Glu146, Glu177 and Gln178), but none of them was observed in EsFer-1. By
      fluorescent quantitative real-time PCR, mRNA transcripts of EsFer-1 and EsFer-2
      were mainly detected in muscle, hepatopancreas and gill, and also marginally
      detectable in gonad, heart and hemocytes. After the crabs were challenged by
      bacteria Listonella anguillarum, the transcriptional levels of both EsFer-1 and
      EsFer-2 in hemocytes were up-regulated twice. In the first up-regulation, the
      mRNA relative expression levels of both EsFer-1 and EsFer-2 reached peak at 3 h
      post-challenge, while in the second up-regulation, they did not reach the highest
      point within the experiment duration. After the fungi Pichia pastoris GS115
      challenge, there was only one transcriptional level peak of both the two
      ferritins, appearing at 6 h post-challenge. These results suggest that secreted
      EsFer-1 and EsFer-2 are crucial proteins in the iron-withholding defense system,
      and play important roles in the innate immune responses in crabs.

PMID- 20045470
TI  - The impact of prior risk experiences on subsequent risky decision-making: the
      role of the insula.
AB  - Risky decision-making is significantly affected by homeostatic states associated
      with different prior risk experiences, yet the neural mechanisms have not been
      well understood. Using functional MRI, we examined how gambling decisions and
      their underlying neural responses were modulated by prior risk experiences, with
      a focus on the insular cortex since it has been implicated in interoception,
      emotion and risky decision-making. Fourteen healthy young participants were
      scanned while performing a gambling task that was designed to simulate daily-life
      risk taking. Prior risk experience was manipulated by presenting participants
      with gambles that they were very likely to accept or gambles that they were
      unlikely to accept. A probe gamble, which was sensitive to individual's risk
      preference, was presented to examine the effect of prior risk experiences (Risk
      vs. Norisk) on subsequent risky decisions. Compared to passing on a gamble
      (Norisk), taking a gamble, especially winning a gamble (Riskwin), was associated
      with significantly stronger activation in the insular and dorsal medial
      prefrontal cortices. Decision making after Norisk was more risky and more likely
      to recruit activation of the insular and anterior cingulate cortices. This
      insular activity during decision making predicted the extent of risky decisions
      both within- and across-subjects, and was also correlated with an individual's
      personality trait of urgency. These findings suggest that the insula plays an
      important role in activating representations of homeostatic states associated
      with the experience of risk, which in turn exerts an influence on subsequent
      decisions.

PMID- 20045471
TI  - Recognition memory for one-trial-unitized word pairs: evidence from event-related
      potentials.
AB  - Performance in tests of associative memory is generally thought to require
      recollection while familiarity cannot support memory for associations. However,
      recent research suggested that familiarity contributes to associative memory when
      the to-be-associated stimuli are unitized during encoding. Here, we investigated
      the electrophysiological correlates of retrieval of word pairs after two
      different encoding conditions. Semantically unrelated word pairs were presented
      as separate lexical units in a sentence frame (non-unitized word pairs) or
      together with a definition that allows to combine word pairs to a new concept
      (unitized word pairs). At test, participants discriminated between word pairs
      that appeared in the same pairing during study, recombined, or new pairs. Memory
      processes were examined by means of event-related potentials (ERPs). An early
      old/new effect with a parietal maximum was found for unitized word pairs while a
      qualitatively different late old/new effect was elicited by non-unitized word
      pairs, only. These findings suggest that one-trial-unitized word pairs are
      recognized differently from non-unitized word pairs. We will discuss the
      possibility that unitization leads to the engagement of specific forms of
      familiarity-conceptual fluency and absolute familiarity.

PMID- 20045472
TI  - The neural correlates of implicit and explicit self-relevant processing.
AB  - Neuroimaging investigations of self-processing have generally focused on the
      neural correlates of explicit self-reflection. However, very little is known
      about the neural basis of implicit self-related processes. We utilized the
      concept of self-schemas to construct a two-task fMRI study that elicited both
      implicit and explicit self-relevant processes. The sample consisted of 18
      participants who were schematic for either athletics or science. In the implicit
      self-relevance task, individuals made non-self-relevant judgments about
      affectively neutral scientific and athletic images. In the explicit self
      reference task, participants judged the self-descriptiveness of adjectives
      related to athletics or science. Implicit and explicit processing of self
      relevant (schematic) material elicited activity in many of the same regions,
      including medial prefrontal cortex, posterior cingulate/precuneus, ventromedial
      prefrontal cortex, subgenual anterior cingulate, amygdala, and ventral striatum.
      We suggest that processing self-related material recruits similar neural networks
      regardless of whether the self-relevance is made explicit or not.

PMID- 20045473
TI  - Neural processing of negative word stimuli concerning body image in patients with
      eating disorders: an fMRI study.
AB  - Eating disorders (EDs) are associated with abnormalities of body image
      perception. The aim of the present study was to investigate the functional
      abnormalities in brain systems during processing of negative words concerning
      body images in patients with EDs. Brain responses to negative words concerning
      body images (task condition) and neutral words (control condition) were measured
      using functional magnetic resonance imaging in 36 patients with EDs (12 with the
      restricting type anorexia nervosa; AN-R, 12 with the binging-purging type
      anorexia nervosa; AN-BP, and 12 with bulimia nervosa; BN) and 12 healthy young
      women. Participants were instructed to select the most negative word from each
      negative body-image word set and to select the most neutral word from each
      neutral word set. In the task relative to the control condition, the right
      amygdala was activated both in patients with AN-R and in patients with AN-BP. The
      left medial prefrontal cortex (mPFC) was activated both in patients with BN and
      in patients with AN-BP. It is suggested that these brain activations may be
      associated with abnormalities of body image perception. Amygdala activation may
      be involved in fearful emotional processing of negative words concerning body
      image and strong fears of gaining weight. One possible interpretation of the
      finding of mPFC activation is that it may reflect an attempt to regulate the
      emotion invoked by the stimuli. These abnormal brain functions may help provide
      better accounts of the psychopathological mechanisms underlying EDs.

PMID- 20045474
TI  - Loss of control during instrumental learning: a source localization study.
AB  - This study used multi-channel electroencephalography (EEG) to investigate
      cortical correlates of response-outcome contingency appraisal as indexed by the
      postimperative negative variation (PINV) during instrumental learning. PINV data
      were subjected to standardized low resolution brain electromagnetic tomography
      (sLORETA) for source localization. Forty-six healthy adult persons underwent a
      forewarned S1-S2 paradigm where response-outcome contingencies varied in three
      consecutive conditions. Initially subjects could control aversive stimulation by
      a correct behavioral response followed by loss of control and subsequent
      restitution of control. Throughout the experiment, reaction times, errors,
      ratings of controllability, arousal, emotional valence and helplessness were
      assessed. Topographical EEG analyses showed that in particular frontal PINV
      magnitudes covaried with the experimental manipulation. Loss of control induced
      extensive response-outcome uncertainty accompanied by a fronto-central PINV
      maximum. sLORETA functional analyses of the PINV revealed that dependent on the
      experimental conditions frontal, temporal and parietal areas seem to be related
      to PINV formation. In particular during loss of control, between-conditions
      sLORETA comparisons found Brodmann Area 24 in the anterior cingulate cortex (ACC)
      to be associated with PINV generation, which was confirmed by correlational
      analyses. These results provide further evidence for the role of the ACC in
      detecting response conflict and its involvement in the generation of the PINV.

PMID- 20045475
TI  - Self-related awareness and emotion regulation.
AB  - The regulation of emotions is an ongoing internal process and often a challenge.
      Current related neural models concern the intended control of reactions towards
      external events, mediated by prefrontal cortex regions upon basal emotion
      processing as in the amygdala. Cognitive strategies to regulate emotions in the
      context of affective disorders or stress reduction, increasingly applied in
      clinical practice, are also related to mindfulness techniques. We questioned
      their effects on neural emotion processing and investigated brain activity during
      purely internal mental self-referential processes of making current emotions and
      self-related cognitions aware. Thirty healthy subjects performed a task
      comprising periods of cognitive self-reflection, of introspection for actual own
      emotions and feelings, and of a neutral condition, while they were scanned with
      functional magnetic resonance imaging. Brain activations of twenty-seven subjects
      during emotion-introspection and self-reflection, and also a conjunction of both,
      were compared with the neutral condition. The conditions of self-reflection and
      emotion-introspection showed distinguishable activations in medial and
      ventrolateral prefrontal areas, in parietal regions and in the amygdala. Notably,
      amygdala activity decreased during emotion-introspection and increased compared
      to 'neutral' during self-reflection. The results indicate that already the self
      referential mental state of making the actual emotional state aware is capable of
      attenuating emotional arousal. This extends current theories of emotion
      regulation and has implications for the application of mindfulness techniques as
      a component of psychotherapeutic strategies in affective disorders and also for
      possible everyday emotion regulation.

PMID- 20045476
TI  - Structural correlates of memory performance with diffusion tensor imaging.
AB  - Aging is associated with a variety of structural and pathological brain changes.
      Memory, or the ability to store and retrieve information, declines significantly
      during aging. In order to characterize the brain micro-structural correlates of
      memory performance, 52 healthy subjects, age 25-82 years, completed a
      computerized non-verbal memory test and were scanned using magnetic resonance
      diffusion tensor imaging. Partial correlation was conducted between DTI
      parameters and memory performance (accuracy and reaction time (RT) for different
      learning stages) controlling for age. A similar correlation pattern was found for
      apparent diffusion coefficient (ADC), FA, and radial and axial diffusivities, but
      correlations between ADC and memory performance were the most informative and are
      therefore reported here. While ADC was correlated with accuracy mainly in
      temporal and frontal cortical regions, it was correlated with RT in temporal and
      frontal white matter pathways, including the inferior longitudinal fasciculus and
      uncinate fasciculus. The task was repeated four times, performance in the first
      repetition was correlated with ADC in frontal white matter and in the fourth
      repetition with ADC in temporal gray matter structures mainly the parahippocapus
      and in the middle temporal gyrus. The localization of the correlations of ADC
      with the different task parameters is in line with previous studies. Thus, inter
      subject variability in memory performance and tissue morphology, as expressed by
      diffusion tensor magnetic resonance imaging, can be used to relate tissue
      microstructures with cognitive performance, and to provide information to
      corroborate other functional localization techniques.

PMID- 20045477
TI  - Distinct profiles of brain atrophy in frontotemporal lobar degeneration caused by
      progranulin and tau mutations.
AB  - Neural network breakdown is a key issue in neurodegenerative disease, but the
      mechanisms are poorly understood. Here we investigated patterns of brain atrophy
      produced by defined molecular lesions in the two common forms of genetically
      mediated frontotemporal lobar degeneration (FTLD). Nine patients with progranulin
      (GRN) mutations and eleven patients with microtubule-associated protein tau
      (MAPT) mutations had T1 MR brain imaging. Brain volumetry and grey and white
      matter voxel-based morphometry (VBM) were used to assess patterns of cross
      sectional atrophy in the two groups. In a subset of patients with longitudinal
      MRI rates of whole-brain atrophy were derived using the brain-boundary-shift
      integral and a VBM-like analysis of voxel-wise longitudinal volume change was
      performed. The GRN mutation group showed asymmetrical atrophy whereas the MAPT
      group showed symmetrical atrophy. Brain volumes were smaller in the GRN group
      with a faster rate of whole-brain atrophy. VBM delineated a common anterior
      cingulate-prefrontal-insular pattern of atrophy in both disease groups.
      Additional disease-specific profiles of grey and white matter loss were
      identified on both cross-sectional and longitudinal imaging: GRN mutations were
      associated with asymmetrical inferior frontal, temporal and inferior parietal
      lobe grey matter atrophy and involvement of long intrahemispheric association
      white matter tracts, whereas MAPT mutations were associated with symmetrical
      anteromedial temporal lobe and orbitofrontal grey matter atrophy and fornix
      involvement. The findings suggest that the effects of GRN and MAPT mutations are
      expressed in partly overlapping but distinct anatomical networks that link
      specific molecular dysfunction with clinical phenotype.

PMID- 20045478
TI  - When I think about me and simulate you: medial rostral prefrontal cortex and self
      referential processes.
AB  - While neuroimaging studies implicate medial rostral prefrontal cortex (mrPFC) in
      self-referential processing, simulation accounts of social cognition suggest that
      this region also supports thinking about other people. This study tested the
      prediction that mrPFC might be involved in appraising the personality traits of
      another person to the degree that this person is perceived as similar to oneself.
      We also examined whether recruiting common processes for thinking about oneself
      and others might impact on subsequent memory for those judgments. Functional MRI
      was used while two factors were crossed: (i) the requirement to engage in
      personality trait or episodic source memory judgments and (ii) the reference for
      these judgments (i.e., oneself or a friend). The results link haemodynamic
      changes in mrPFC to both personality judgments about oneself and subsequent
      episodic memory retrieval of these judgments. The degree to which BOLD signal in
      this region was also associated with thinking about others correlated with
      perceived similarity in both tasks, thus corroborating simulation accounts.
      Moreover, participants who perceived themselves as having similar traits to their
      friends tended to be poorer at remembering whether they had made trait judgments
      in reference to themselves or their friend. This behavioral effect was reflected
      in the BOLD signal in mrPFC: there was a positive correlation between signal
      change for self versus friend judgments and subsequent memory for the reference
      of such judgments. The results suggest that investigations of mrPFC activity in
      the context of self/other judgments should take into account this psychological
      similarity effect.

PMID- 20045479
TI  - Randomized phase III trial of pegfilgrastim versus filgrastim after autologus
      peripheral blood stem cell transplantation.
AB  - Nonrandomized trials suggest that pegfilgrastim, a pegylated granulocyte colony
      stimulating factor, could be used in lieu of filgrastim after autologus
      peripheral blood stem cell transplantation. This phase III, randomized, double
      blinded, placebo-controlled trial compared the efficacy, costs, and safety of
      single-dose pegfilgrastim (single 6 mg dose) versus daily filgrastim (5
      microg/kg/day) for this indication. Seventy-eight patients, matched for age, sex,
      underlying disease, stage, and CD34/kg transplant dose were enrolled. Cytokines
      were started on day +1 posttransplant and continued to an absolute neutrophil
      count (ANC) of 5x10(9)/L for 3 days or 10x10(9)/L for 1 day. The median time to
      neutrophil engraftment (ANC >1.5x10(9)/L for 3 days or 5x10(9)/L for 1 day) was
      the same in both groups (12 days). No differences in platelet engraftment (11
      versus 13 days), number of platelet transfusions (5 versus 4), percent with
      positive cultures for bacterial pathogens (23% versus 15%), days of fever (1
      versus 2), deaths prior to engraftment (1 versus 1), or duration of hospital stay
      (19 versus 19 days) were seen between the pegfilgrastim and filgrastim groups,
      respectively. Using the average wholesale price for doses used in this trial,
      there was a per-patient savings of $961 for the pegfilgrastim group (P < .001).
      This phase III study failed to demonstrate a difference in time to neutrophil
      engraftment or any clinical sequelae between pegfilgrastim and filgrastim when
      given post-APBSCT, with pegfilgrastim achieving a cost savings over filgrastim.

PMID- 20045480
TI  - UDP-GlC:glycoprotein glucosyltransferase-glucosidase II, the ying-yang of the ER
      quality control.
AB  - The N-glycan-dependent quality control of glycoprotein folding prevents
      endoplasmic to Golgi exit of folding intermediates, irreparably misfolded
      glycoproteins and incompletely assembled multimeric complexes. It also enhances
      folding efficiency by preventing aggregation and facilitating formation of proper
      disulfide bonds. The control mechanism essentially involves four components,
      resident lectin-chaperones that recognize monoglucosylated polymannose glycans, a
      lectin-associated oxidoreductase acting on monoglucosylated glycoproteins, a
      glucosyltransferase that creates monoglucosytlated epitopes in protein-linked
      glycans and a glucosidase that removes the glucose units added by the
      glucosyltransferase. This last enzyme is the only mechanism component sensing
      glycoprotein conformations as it creates monoglucosylated glycans exclusively in
      not properly folded species or in not completely assembled complexes. The
      glucosidase is a dimeric heterodimer composed of a catalytic subunit and an
      additional one that is partially responsible for the ER localization of the
      enzyme and for the enhancement of the deglucosylation rate as its mannose 6
      phosphate receptor homologous domain presents the substrate to the catalytic
      site. This review deals with our present knowledge on the glucosyltransferase and
      the glucosidase.

PMID- 20045482
TI  - Distinct enzymatic and cellular characteristics of two secretory phospholipases
      A2 in the filamentous fungus Aspergillus oryzae.
AB  - Microbial secretory phospholipases A(2) (sPLA(2)s) are among the last discovered
      and least known members of this functionally diverse family of enzymes. We
      analyzed here two sPLA(2)s, named sPlaA and sPlaB, of the filamentous ascomycete
      Aspergillus oryzae. sPlaA and sPlaB consist of 222 and 160 amino acids,
      respectively, and share the conserved Cys and catalytic His-Asp residues typical
      of microbial sPLA(2)s. Two sPLA(2)s differ in pH optimum, Ca(2+) requirement and
      expression profile. The splaA mRNA was strongly upregulated in response to carbon
      starvation, oxidative stress and during conidiation, while splaB was
      constitutively expressed at low levels and was weakly upregulated by heat shock.
      Experiments with sPLA(2) overexpressing strains demonstrated that two enzymes
      produce subtly different phospholipid composition variations and also differ in
      their subcellular localization: sPlaA is most abundant in hyphal tips and
      secreted to the medium, whereas sPlaB predominantly localizes to the ER-like
      intracellular compartment. Both sPLA(2) overexpressing strains were defective in
      conidiation, which was more pronounced for sPlaB overexpressors. Although no
      major morphological abnormality was detected in either DeltasplaA or DeltasplaB
      mutants, hyphal growth of DeltasplaB, but not that of DeltasplaA, displayed
      increased sensitivity to H(2)O(2) treatment. These data indicate that two A.
      oryzae sPLA(2) enzymes display distinct, presumably non-redundant, physiological
      functions.

PMID- 20045483
TI  - Promoting effects of IL-13 on Ca2+ release and store-operated Ca2+ entry in
      airway smooth muscle cells.
AB  - Th2 cytokine interleukin (IL)-13 plays a central role in the pathogenesis of
      allergic asthma. IL-13 exhibits a direct effect on airway smooth muscle cells
      (ASMCs) to cause airway hyperresponsiveness. IL-13 has been demonstrated to
      regulate Ca(2+) signaling in ASMCs, but the underlying mechanisms are not fully
      understood. Store-operated Ca(2+) entry (SOCE) plays an important role in
      regulating Ca(2+) signaling and cellular responses of ASMCs, whether IL-13
      affects SOCE in ASMCs has not been reported. In this study, by using confocal
      Ca(2+) fluorescence imaging, we found that IL-13 (10 ng/ml) treatment increased
      basal intracellular Ca(2+) ([Ca(2+)](i)) level, Ca(2+) release and SOCE induced
      by SERCA inhibitor thapsigargin in rat bronchial smooth muscle cells. The
      glucocorticoid dexamethasone and the short-acting beta2 adrenergic agonist (beta2
      agonist) salbutamol suppressed IL-13-augumented basal [Ca(2+)](i), Ca(2+) release
      and SOCE, whereas the long-acting beta2 agonist salmeterol had no effect on
      altered Ca(2+) signaling in IL-13-treated ASMCs. Membrane-permeable cAMP analog
      dibutyryl-cAMP (db-cAMP) similarly decreased Ca(2+) release and SOCE induced by
      thapsigargin in IL-13-treated ASMCs, confirmed a role of cAMP/PKA signaling
      pathway in the regulation of SOCE. IL-13 promoted the proliferation of ASMCs
      stimulated by serum; this effect was inhibited by nonspecific Ca(2+) channel
      blockers SKF-96365 and NiCl(2), by salmeterol, but not by salbutamol and
      dexamethasone. IL-13 treatment did not change the expression of SOC channel
      associated molecules STIM1, Orai1 and TRPC1 at mRNA level. Our findings
      identified a promoting effect of IL-13 on Ca(2+) release and SOCE in ASMCs, which
      partially contributes to its effect on the proliferation of ASMCs; the
      differences of glucocorticoids and beta2 agonists in inhibiting Ca(2+) signal and
      proliferation potentiated by IL-13 suggest that these therapies of asthma may
      have distinct effect on the relief of airway contraction and remodeling in
      bronchial asthma.

PMID- 20045481
TI  - The PARL family of mitochondrial rhomboid proteases.
AB  - Rhomboids are an ancient and conserved family of intramembrane-cleaving
      proteases, a small group of proteolytic enzymes capable of hydrolyzing a peptide
      bond within a transmembrane helix that anchors a substrate protein to the
      membrane. Mitochondrial rhomboids evolved in eukaryotes to coordinate a critical
      aspect of cell biology, the regulation of mitochondrial membranes dynamics. This
      function appears to have required the emergence of a structural feature that is
      unique among all other rhomboids: an additional transmembrane helix (TMH)
      positioned at the N-terminus of six TMHs that form the core proteolytic domain of
      all prokaryotic and eukaryotic rhomboids. This "1+6" structure, which is shared
      only among mitochondrial rhomboids, defines a subfamily of rhomboids with the
      prototypical family member being mammalian Parl. Here, we present the findings
      that in 11 years have elevated mitochondrial rhomboids as the gatekeepers of
      mitochondrial dynamics and apoptosis; further, we discuss the aspects of their
      biology that are bound to introduce new paradigm shifts in our understanding of
      how the organelle uses this unique type of protease to govern stress, signaling
      to the nucleus, and other key mitochondrial activities in health and disease.

PMID- 20045484
TI  - Locomotor performance in the Drosophila brain mutant drop-dead.
AB  - Mutation of the drop-dead gene in Drosophila causes early death of the adult
      animal. After hatching from pupae, drop-dead mutants increasingly lose body
      control and typically die within ten days. Drop-dead carries an X-chromosomal
      recessive mutation that causes brain degeneration, due to a loss in glia
      function. Recent results attribute this functional deficiency to a component
      required to form the tracheolar respiratory apparatus and thus to a reduction of
      tracheal oxygen supply. If the reduction of respiratory capacity is the primary
      reason for brain degeneration, locomotor capacity of drop-dead should be
      significantly impaired. We thus determined running performance and locomotor
      motivation of drop-dead(1) mutants at ages between one and five days. The mutant
      achieves similar mean and maximum forward speeds during running of approximately
      1.5 and 10 mms(-1), respectively, as wild type flies. Thus metabolic capacity
      required for running seems not to be compromised. Drop-dead(1) flies, however,
      are significantly more active (34%) and also have a higher motivation (33%) to
      initiate running. Heading instability during forward running was increased by 17%
      compared to wild type and tended to increase with age. These findings are
      consistent with the previously reported loss in body control in the mutant and
      thus demonstrate the significance of the drop-dead gene for running behaviour in
      Drosophila.

PMID- 20045485
TI  - Response of Mytilus galloprovincialis (L.) to increasing seawater temperature and
      to marteliosis: metabolic and physiological parameters.
AB  - In the context of climate change the present work aimed to illustrate whether the
      energetic and metabolic pattern of mussels Mytilus galloprovincialis will be
      affected by increase in the temperature of seawater. Moreover we examined whether
      an outbreak of Marteilia sp. infestation as a result of increase in sea water
      temperature will impair the energetic balance of mussels. M. galloprovincialis
      was acclimated at 18 degrees C, 24 degrees C, 26 degrees C and 28 degrees C for
      30 days and the energetic pattern of its tissues was estimated by determining the
      factor Scope for Growth (SFG), while the metabolic pattern of mussels was
      estimated by determining the activities of pyruvate kinase (PK) and
      phosphoenolpyruvate carboxykinase (PEPCK). The decrease in PK activity and the
      decrease in the ratio PK/PEPCK indicated an activation of anaerobic component of
      metabolism during acclimation of mussels at temperature 24 degrees C. At
      temperatures higher than 24 degrees C the values of SFG turned negative probably
      associated with a significant reduction in clearance rate. Compared to the non
      infected mussels, the SFG values of infected mussels were significantly lower
      (P<0.05). These differences were attributed to the higher filtration rate and the
      lower absorption efficiency detected in the infected mussels. Also the degree of
      SFG reduction is dependent on the intensity levels of infection by Marteilia sp.

PMID- 20045486
TI  - Circulating tumour-derived predictive biomarkers in oncology.
AB  - Molecular characterization of tumour material will become increasingly important
      in selecting patients for clinical trials and offering appropriate treatment for
      patients in clinical practice. Recent advances in the field have indicated that
      the molecular characteristics of a tumour can be determined from circulating
      tumour cells and circulating tumour DNA; thus, a simple blood sample could
      provide these data in a simple, convenient and efficient manner. This article
      discusses progress towards guiding treatment decisions through measuring tumour
      derived factors in the circulation.

PMID- 20045487
TI  - Trichuris or Capillaria?

PMID- 20045488
TI  - Differential transcription of genes involved in peroxisome proliferation in
      thicklip grey mullets Chelon labrosus injected with benzo(a)pyrene.
AB  - Benzo(a)pyrene (B(a)P) is a mutagenic polycyclic aromatic hydrocarbon (PAH)
      commonly released into the environment. B(a)P induces phase I biotransformation
      metabolism and peroxisome proliferation which is characterised in rodents by
      increased peroxisomal volume density, accompanied by the transcriptional
      induction of peroxisomal proteins. The aim of the present work was to study
      peroxisome proliferation at the transcriptional level, in comparison to the
      transcription of the well-characterised cytochrome P450 1A gene (cyp1a) in the
      thicklip grey mullet Chelon labrosus. For this purpose, genes coding for the
      major peroxisomal membrane protein PMP70 and CYP1A were cloned using degenerate
      primers. Then juvenile mullets were single injected with B(a)P (5mg/kg) and
      transcription of palmitoyl-CoA oxidase (aox1), multifunctional protein (mfp1), 3
      ketoacyl-CoA thiolase (thio), Delta(2),Delta(4)dienoyl-CoA reductase 2, pmp70,
      catalase and cyp1a was semi-quantified in liver and gills 1 and 7days after the
      injection. Transcription of aox1 and cyp1a was induced in gills 1day after B(a)P
      injection. Cyp1a transcription was also induced in mullet liver one day after
      injection, indicating that B(a)P was available for the liver. This was further
      proved by the significant accumulation of B(a)P-like metabolites in bile 7days
      after the injection. In liver, aox1, mfp1 and thio transcription was induced at
      day 1 followed by the induction of catalase transcription at day 7 that may
      reflect a response to an oxidative stress caused by B(a)P itself or by
      oxyradicals produced through the biotransformation metabolism and the peroxisomal
      beta-oxidation. These hepatic responses were not reflected at AOX1 activity
      level. In conclusion, it has been shown for the first time that the three enzymes
      in the fish peroxisomal beta-oxidation pathway are transcriptionally induced by
      B(a)P. It remains to be tested whether this enhanced transcription is reflected
      in an increase in the volume of peroxisomes.

PMID- 20045489
TI  - Tissue-specific inhibition and recovery of esterase activities in Lumbricus
      terrestris experimentally exposed to chlorpyrifos.
AB  - Exposure and effect assessment of organophosphate (OP) pesticides generally
      involves the use of cholinesterase (ChE) inhibition. In earthworm, this enzyme
      activity is often measured in homogenates from the whole organism. Here we
      examine the tissue-specific response of ChE and carboxylesterase (CE) activities
      in Lumbricus terrestris experimentally exposed to chlorpyrifos-spiked field
      soils. Esterases were measured in different gut segments and in the seminal
      vesicles of earthworms following acute exposure (2 d) to the OP and during 35d of
      a recovery period. We found that inhibition of both esterase activities was
      dependent on the tissue. Cholinesterase activity decreased in the pharynx, crop,
      foregut and seminal vesicles in a concentration-dependent way, whereas CE
      activity (4-nitrophenyl valerate) was strongly inhibited in these tissues.
      Gizzard CE activity was not inhibited by the OP, even an increase of enzyme
      activity was evident during the recovery period. These results suggest that both
      esterases should be determined jointly in selected tissues of earthworms.
      Moreover, the high levels of gut CE activity and its inhibition and recovery
      dynamic following OP exposure suggest that this esterase could play an important
      role as an enzymatic barrier against OP uptake from the ingested contaminated
      soil.

PMID- 20045490
TI  - Multiple biomarkers of pollution effects in caged mussels on the Greek coastline.
AB  - A suite of biomarkers was measured in caged mussels at areas impacted by
      different anthropogenic activities along the Greek coastline to assess biological
      effects of environmental pollution. Mussels were caged at coastal sites in the
      vicinity of major cities, in areas influenced by major industries, agricultural
      practices and in islands away from known sources of pollution. Biomarkers
      indicative of neurotoxicity (acetylcholinesterase, AchE), oxidative stress
      (catalase, CAT), phase II biotransformation of xenobiotics (glutathione S
      transferase, GST), metal exposure (metallothioneins, MTs) and protein synthesis
      (RNA:DNA ratio) were measured to assess effects of various types of pollutants.
      AchE activity proved to be the most responsive biomarker with decreased values at
      sites influenced by agricultural, urban and industrial activities. Decreased CAT
      and GST activities and increased MTs levels were recorded at a number of
      anthropogenic-impacted sites. RNA:DNA ratio showed a biphasic response as both
      high and low values were found at impacted sites. Principal component analysis
      clearly distinguished sites receiving pollution inputs from non-polluted sites.
      The combination of the selected biomarkers used in caged mussels resulted useful
      in the assessment of the effects of environmental pollution.

PMID- 20045491
TI  - Molecular characterization and expression of vitellogenin (Vg) genes from the
      cyclopoid copepod, Paracyclopina nana exposed to heavy metals.
AB  - Induction of vitellogenin (Vg) has been used as a biomarker of exposure to heavy
      metals and endocrine-disruption chemicals (EDCs) in aquatic organisms. Here, we
      identified the full-length Vg1 and Vg2 sequence from the brackish water copepod,
      Paracyclopina nana. Vg1 gene contained 5718bp of the open reading frame (ORF)
      that encoded the putative protein of 1905 amino acids residues, while Vg2 gene
      consisted of 5442bp of ORF, encoding the putative protein of 1813 amino acids
      residues. P. nana Vgs showed highly conserved domains in the N-terminal region.
      The phylogenetic analysis revealed that P. nana Vgs are distinct from other
      arthropods, such as insects and decapods, as it formed a clade with other
      copepods, Tigriopus japonicus and salmon louse (Lepeophtheirus salmonis). The
      expression of Vg transcripts was detectable after the copepodid stages 4-5.
      Female copepods expressed over 83 times and 223 times more Vg1 and Vg2
      transcripts, respectively, than males. When copepods were exposed to heavy metals
      (0.1mg/L Cd, 0.4mg/L Cu, and 2mg/L AsIII) for 24, 48, 72, and 96h, P. nana Vg
      transcripts were highly induced in a time-dependent manner. Interestingly, Vg2
      gene was more susceptible than Vg1 to trace heavy metal exposure. This finding
      indicates that P. nana Vgs provide a potential indicator for assessing the toxic
      effect of heavy metals. In addition, we suggest P. nana as a potential model
      species for risk-assessment to environmental pollutants in brackish water.

PMID- 20045492
TI  - Fatty acid composition and gene expression profiles are altered in aryl
      hydrocarbon receptor-1 mutant Caenorhabditis elegans.
AB  - The aryl hydrocarbon receptor (AHR) is a eukaryotic transcription factor that
      plays an essential role in neuronal, immune, vascular, hepatic and hematopoietic
      development. In mammals, AHR induces metabolism-associated genes in response to
      xenobiotics. AHR is evolutionarily conserved, and the C. elegans AHR ortholog
      likely shares many physiologic functions with the mammalian version. While the
      role of AHR in development is known, the molecular basis of AHR action is less
      well understood. To understand the physiologic role of AHR in C. elegans, a
      combination of fatty acid profiling, transcriptomics, and phenotyping approaches
      was used. Fatty acid profiles from L4 larval stage whole animals indicated that
      C17isoA, C18:1n9t, C20:3n6 and C20:4n6 were significantly increased in an ahr-1
      mutant compared to wild-type. Consistent with these changes, we observed a
      significant 5.8 fold increase in fat-7, and 1.7-1.9 fold increases in elo-5, nhr
      49, and mdt-15 gene expression during the L4 stage. The ahr-1(ju145) mutant
      displayed deficits in growth and development including a reduced number of eggs
      laid, a higher proportion of dead embryos, delay in time to reach L4 stage, and
      movement deficits including a fewer number of body bends and a longer defecation
      cycle. To understand global effects of AHR-1 on transcription, microarray
      analysis was performed on L1 stage animals. Expression changes (324 under- and
      238 over-expressed) were found in genes associated with metabolism, growth, and
      development. These results indicate a role for C. elegans AHR in regulating fatty
      acid composition and in contributing to some aspects of development. Since the
      transcriptional control of AHR targets may be evolutionarily conserved, these
      results provide a deeper understanding of the molecular actions of AHR in a model
      invertebrate system that may be informative for higher organisms.

PMID- 20045493
TI  - MeuTXKbeta1, a scorpion venom-derived two-domain potassium channel toxin-like
      peptide with cytolytic activity.
AB  - Recent studies have demonstrated that scorpion venom contains unique two-domain
      peptides with the peculiarity of possessing different functions, i.e. neurotoxic
      and cytolytic activities. Here we report systematic characterization of a new two
      domain peptide (named MeuTXKbeta1) belonging to the TsTXKbeta molecular subfamily
      from the scorpion Mesobuthus eupeus by molecular cloning, biochemical
      purification, recombinant expression, functional assays, CD and NMR studies. Its
      full-length bioactive form as well as 1-21 and 22-72 fragments (named N(1-21) and
      C(22-72), respectively) was produced in Escherichia coli by an on-column
      refolding approach. Recombinant peptide (rMeuTXKbeta1) exhibited a low affinity
      for K(+) channels and cytolytic effects against bacteria and several eukaryotic
      cells. N(1-21) was found to preserve anti-Plasmodium activity in contrast to
      haemolytic activity, whereas C(22-72) retains these two activities. Circular
      dichroism analysis demonstrates that rMeuTXKbeta1 presents a typical scorpion
      toxin scaffold in water and its alpha-helical content largely increases in a
      membrane-mimicking environment, consistent with the NMR structure of N(1-21) and
      an ab initio structure model of MeuTXKbeta1 predicted using I-TASSER algorithm.
      Our structural and functional data clearly indicate an evolutionary link between
      TsTXKbeta-related peptides and antiparasitic scorpines which both comprise the
      betaSPN (beta-KTxs and scorpines) family.

PMID- 20045495
TI  - Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome
      foetuses.
AB  - Klinefelter syndrome is a sex chromosomal abnormality (47, XXY karyotype),
      occurring approximately in 1 in 1000 male live births. In the present study
      proteomic analysis was performed in twelve 2nd trimester amniotic fluid samples,
      eight coming from pregnancies with normal males and four with Klinefelter
      syndrome foetuses, as shown by routine prenatal cytogenetic analysis. Samples
      were analysed by 2-DE, coupled with MALDI-TOF-MS analysis. Three proteins
      (Ceruloplasmin, Alpha-1-antitrypsin and Zinc-alpha-2-glycoprotein) were found to
      be up-regulated in samples obtained from pregnancies with Klinefelter syndrome
      foetuses, whereas four proteins (Apolipoprotein A-I, Plasma retinol-binding
      protein, Gelsolin, and Vitamin D-binding protein) were down regulated when
      compared to proteins detected in samples from normal foetuses. The differential
      expression of Ceruloplasmin, Apolipoprotein A-I and Plasma retinol-binding
      protein was further confirmed by immunoblotting. Since these proteins are likely
      to cross the placenta barrier and be detected in maternal plasma they could be
      used as biomarkers for the non-invasive prenatal diagnosis of Klinefelter
      syndrome.

PMID- 20045494
TI  - Proteins secreted by embryonic stem cells activate cardiomyocytes through ligand
      binding pathways.
AB  - Human embryonic stem cells (hESC) underlie embryogenesis but paracrine signals
      associated with the process are unknown. This study was designed to 1) profile
      native proteins secreted by undifferentiated hESC and 2) determine their
      biological effects on primary neonatal cardiomyocytes. We utilized multi-analyte,
      immunochemical assays to characterize media conditioned by undifferentiated hESC
      versus unconditioned media. Expression profiling was performed on cardiomyocytes
      subjected to these different media conditions and altered transcripts were mapped
      to critical pathways. Thirty-two of 109 proteins were significantly elevated in
      conditioned media ranging in concentration from thrombospondin (57.2+/-5.0 ng/ml)
      to nerve growth factor (7.4+/-1.2pg/ml) and comprising chemokines, cytokines,
      growth factors, and proteins involved in cell adhesion and extracellular matrix
      remodeling. Conditioned media induced karyokinesis, cytokinesis and proliferation
      in mono- and binucleate cardiomyocytes. Pathway analysis revealed comprehensive
      activation of the ROCK 1 and 2 G-protein coupled receptor (GPCR) pathway
      associated with cytokinesis, and the RAS/RAF/MEK/ERK receptor tyrosine kinase
      (RTK) and JAK/STAT-cytokine pathway involved in cell cycle progression. These
      results provide a partial database of proteins secreted by pluripotent hESC that
      potentiate cell division in cardiomyocytes via a paracrine mechanism suggesting a
      potential role for these stem cell factors in cardiogenesis and cardiac repair.

PMID- 20045496
TI  - Studies on glyphosate-induced carcinogenicity in mouse skin: a proteomic
      approach.
AB  - Glyphosate is a widely used broad spectrum herbicide, reported to induce various
      toxic effects in non-target species, but its carcinogenic potential is still
      unknown. Here we showed the carcinogenic effects of glyphosate using 2-stage
      mouse skin carcinogenesis model and proteomic analysis. Carcinogenicity study
      revealed that glyphosate has tumor promoting activity. Proteomic analysis using 2
      dimensional gel electrophoresis and mass spectrometry showed that 22 spots were
      differentially expressed (>2 fold) on glyphosate, 7, 12-dimethylbenz[a]anthracene
      (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) application over untreated
      control. Among them, 9 proteins (translation elongation factor eEF-1 alpha chain,
      carbonic anhydrase III, annexin II, calcyclin, fab fragment anti-VEGF antibody,
      peroxiredoxin-2, superoxide dismutase [Cu-Zn], stefin A3, and calgranulin-B) were
      common and showed similar expression pattern in glyphosate and TPA-treated mouse
      skin. These proteins are known to be involved in several key processes like
      apoptosis and growth-inhibition, anti-oxidant responses, etc. The up-regulation
      of calcyclin, calgranulin-B and down-regulation of superoxide dismutase [Cu-Zn]
      was further confirmed by immunoblotting, indicating that these proteins can be
      good candidate biomarkers for skin carcinogenesis induced by glyphosate.
      Altogether, these results suggested that glyphosate has tumor promoting potential
      in skin carcinogenesis and its mechanism seems to be similar to TPA.

PMID- 20045498
TI  - Low-density lipoprotein receptor-related protein 5 (LRP5) variation in fracture
      prone children.
AB  - OBJECTIVE: Recent studies have confirmed that the low-density lipoprotein
      receptor-related protein 5 gene (LRP5), plays a role in bone mass accrual and in
      susceptibility to osteoporotic fractures in adults. This study evaluated whether
      LRP5 variation is implicated in childhood fractures. PATIENTS AND METHODS: During
      an epidemiological study on childhood fractures, comprising 1390 consecutive
      Finnish children with an acute fracture, we recruited fracture-prone 4-16 years
      old children, who had a history of at least two low-energy long bone fractures
      before age 10 years or three low-energy long bone fractures before age 16 years,
      and/or at least one low-energy vertebral compression fracture. A total of 72
      (5.2%) children fulfilled these inclusion criteria; DNA samples were obtained for
      66 of them. All 23 exons and exon-intron boundaries of the LRP5 gene were
      sequenced; the identified variants were analyzed in 235 healthy Finnish control
      samples. RESULTS: Sequencing revealed 15 coding region missense or silent
      variants with unknown functional consequences. No obvious loss-of-function
      mutations such as deletions, insertions, or changes resulting in premature
      termination codon or altered splicing were identified. Phenotyping of the proband
      and parents, and genotyping of the parents, in 9 families with novel or rare
      variants showed no obvious correlation between any of the LRP5 variants and
      fractures. CONCLUSIONS: Our study shows that in children LRP5 mutations are not a
      common cause of increased fractures. The observed rare LRP5 variants may together
      with unfavorable environmental and other genetic factors contribute to childhood
      fractures, but further studies are needed to confirm their functional
      significance and biological pathways through which this may occur. Our findings
      suggest that systematic LRP5 screening is not indicated in children with
      recurrent fractures.

PMID- 20045497
TI  - Effects of statins vs. non-statin lipid-lowering therapy on bone formation and
      bone mineral density biomarkers in patients with hyperlipidemia.
AB  - INTRODUCTION: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, named statins, are well-established cholesterol-lowering drugs able
      to reduce cardiovascular risk in hypercholesterolemic patients. The possible
      effect of statin on bone tissue, so-called pleiotropic effects has received
      particular attention. Studies reported a positive effect of statin on bone tissue
      in both of animal and human study by enhancing the expression of the bone
      morphogenetic proteins (BMPs), in particular of BMP2, which in turn leads to
      osteoblast differentiation and bone formation including interfering with
      osteoclastic activity. In a systematic review, the lipophilic statin as
      simvastatin had positive effect to bone mineral density (BMD) better than the
      more hydrophilic statin such as atorvastatin and fluvastatin. This study was
      aimed to compare efficacy of medical therapy between HMG-CoA reductase inhibitor
      and non-HMG-CoA reductase inhibitor group to changing of bone mineral density and
      bone markers in the patients with hyperlipidemia. MATERIALS AND METHODS: A
      prospective randomized control trial study enrolled the 212 hyperlipidemia with
      osteopenia patients to study in year 2006-2008. All subjects were randomized to 2
      groups between statin and non-statin group; the patients were screened by
      inclusion criteria and measured in bone mineral density (BMD), bone marker and
      blood chemistry. All data were analyzed by difference of changing in bone marker
      and BMD between statin and non-statin groups using paired t test. RESULTS: The
      present study showed 212 hyperlipidemia with osteopenia patients of which 106
      patients in statin group had mean age (63.17+/-9.51 years) and the same number of
      patients in non-statin group had mean age (60.96+/-8.9 years). All subjects were
      63 patients in male and 149 patients in female. Difference of bone formation
      marker and BMD between after and before was significantly higher than in statin
      group and the difference of bone resorption marker was also significantly lower
      than in statin group. CONCLUSION: The lipophilic statin as moderate to high dose
      of simvastatin had beneficial positive effect to increasing BMD and could be
      additive use for prevention of bone loss in hyperlipidemia patients.

PMID- 20045499
TI  - Muscle loss and bone loss: master and slave?

PMID- 20045501
TI  - Skin reaction to vaccination already before injection.

PMID- 20045500
TI  - HSP65 DNA as therapeutic strategy to treat experimental paracoccidioidomycosis.
AB  - The conventional treatment for paracoccidioidomycosis, the most prevalent mycosis
      in Latin America, involves long periods of therapy resulting in sequels and high
      frequency of relapses. The search for new alternatives of treatment is necessary.
      Previously, we have demonstrated that the hsp65 gene from Mycobacterium leprae
      shows prophylactic effects against murine paracoccidioidomycosis. Here, we tested
      the DNAhsp65 immunotherapy in BALB/c mice infected with Paracoccidioides
      brasiliensis, the agent of paracoccidioidomycosis. We observed an increase of Th1
      cytokines accompanied by a reduction in fungal burden and pulmonary injury. These
      results provide new prospects for immunotherapy of paracoccidioidomycosis and
      other mycoses.

PMID- 20045502
TI  - Structure-activity relationship of lipopeptide Group A streptococcus (GAS)
      vaccine candidates on toll-like receptor 2.
AB  - Incorporation of lipoamino acids (LAAs) into peptide structures effectively
      imparts self-adjuvanting activity onto otherwise ineffective immunogens. Our
      fully synthetic lipopeptide vaccine candidates against group A streptococcus
      (GAS) were composed of J14 as a target GAS B-cell epitope alongside a universal
      helper T-cell epitope (P25) and a LAA-based lipid moiety. In the current study,
      we investigated the ability of our lipopeptides to activate nuclear factor-kappaB
      (NF-kappaB) in a toll-like receptor-2 (TLR2)-dependent manner as the possible
      mode of action and reported the structure-function requirements for novel TLR2
      targeting lipopeptides based on LAAs. The NF-kappaB activation was dependent on
      the dose and the length of the alkyl chains of the incorporated lipid moieties
      with the hierarchy LAA 3 (16 carbons)>LAA 2 (14 carbons)>LAA 1 (12 carbons). The
      position of the lipid moiety (C-terminus vs. N(epsilon)-terminus of the central
      lysine residue) does not significantly affect NF-kappaB activation. Lipopeptides
      containing different copies of LAA 3 were synthesized and the di-lipidated
      analogue was the most effective in NFkappaB activation.

PMID- 20045503
TI  - Spontaneous labor onset: is it immunologically mediated?
AB  - OBJECTIVE: The investigators tested the hypothesis that maternal-fetal immune
      interactions could be important in initiating spontaneous labor onset by
      examining if labor was delayed when fetuses share maternal HLA antigen types.
      STUDY DESIGN: HLA antigen types A, B, and DR in 200 Danish mother-infant pairs
      delivering in 42-44 weeks (postterm) were compared with 195 mother-infant pairs
      delivering in 37-40 weeks (term). RESULTS: Sharing of HLA A and B antigens was
      more common than expected in postterm deliveries. Odds ratios were 1.54 (95%
      confidence interval [CI], 1.01-2.35) and 1.75 (95% CI, 0.87-3.52), respectively
      (risk per shared antigen: 1.40 [95% CI, 1.04-1.90] per unit increase). Adding
      stringent birth-length criteria for postmaturity (92 cases; 168 controls)
      strengthened risks associated with antigen sharing to 1.57 (95% CI, 0.90-2.74)
      and 2.60 (95% CI, 1.15-5.88), respectively (risk per shared antigen: 1.60 (95%
      CI, 1.10-2.32). CONCLUSION: Postterm-delivered infants had more HLA A and B
      antigens in common with their mothers, suggesting that recognition of HLA antigen
      differences by adaptive immunity may have a role in triggering labor onset.

PMID- 20045504
TI  - Placenta previa.

PMID- 20045506
TI  - Social disparity and the use of intrapartum epidural analgesia in a publicly
      funded health care system.
AB  - OBJECTIVE: We sought to examine the difference in use of labor epidural analgesia
      among women from different neighborhood socioeconomic groups. STUDY DESIGN:
      Neighborhood socioeconomic variables from the 2001 Canadian Census were linked to
      singleton vaginal births from the Niday perinatal database (2004-2006) in
      Ontario, Canada. Births were divided into income and education groups by
      quintiles. Generalized estimating equations were employed to evaluate the
      association between labor epidural and neighborhood socioeconomic status.
      Supplementary analysis was conducted after stratifying data by hospital types.
      RESULTS: Compared with those from the richest neighborhood, women from the
      poorest quintile were the least likely to receive labor epidural analgesia (odds
      ratio [OR], 0.59; 95% confidence interval [CI], 0.58-0.61). The differences were
      smallest in teaching hospitals (OR, 0.73; 95% CI, 0.67-0.79) and largest in small
      community hospitals (OR, 0.57; 95% CI, 0.50-0.64). Similar association was found
      in neighborhood education quintiles. CONCLUSION: The use of labor epidural
      analgesia is decreased with decreasing neighborhood economic and education
      levels.

PMID- 20045507
TI  - Physical and biological properties of yam as a saliva substitute.
AB  - OBJECTIVE: The purpose of this study was to investigate the viscosity and
      wettability of a water-soluble extract of yam and its effects on lysozyme and
      peroxidase activities. DESIGN: Human whole saliva, yam tuber, hen egg-white
      lysozyme, and bovine lactoperoxidase were used. Viscosity was measured with a
      cone-and-plate digital viscometer, while wettability was determined by measuring
      the contact angle. Lysozyme activity was determined by the turbidimetric method.
      Peroxidase activity was determined using the NbsSCN assay. Hydroxyapatite beads
      were used as a solid-phase. RESULTS: The viscosity of the yam solution was
      proportional to its concentration, with diluted yam solutions at 1:5 and 1:10 in
      simulated salivary buffer displaying similar viscosity values to unstimulated
      whole saliva and stimulated whole saliva, respectively. The contact angle of yam
      solution was not significantly different according to the tested materials or yam
      concentrations. Contact angles of yam solutions on acrylic resin were higher than
      those of human saliva. Yam affected lysozyme and peroxidase activities, and those
      effects were different on the hydroxyapatite surface versus in solution.
      Hydroxyapatite-adsorbed yam increased subsequent adsorption of lysozyme and
      peroxidase. CONCLUSION: We objectively confirmed the similarity of the
      viscoelastic properties of yam and human saliva, suggesting a role for yam in the
      development of effective saliva substitutes.

PMID- 20045508
TI  - A cocaine cue acts as an incentive stimulus in some but not others: implications
      for addiction.
AB  - BACKGROUND: In addicts drug cues attract attention, elicit approach, and motivate
      drug-seeking and drug-taking behavior, and addicts find it difficult to resist
      such cues. In preclinical studies we have found, however, that food cues acquire
      incentive motivational properties only in a subset of individuals. For example, a
      food cue becomes attractive, eliciting approach and engagement with it, and acts
      as an effective conditional reinforcer in some rats but not others. We asked,
      therefore, whether rats that have a propensity to attribute incentive salience to
      a food cue are the same ones that attribute incentive value to a drug (cocaine)
      cue. METHODS: We first used a Pavlovian conditioned approach procedure to
      determine which individual rats attributed incentive salience to a food cue. A
      second cue was then associated with the IV self-administration of cocaine. Later,
      the ability of the cocaine cue to maintain self-administration behavior and to
      reinstate self-administration after extinction was assessed. RESULTS: We report
      that in individuals that had a propensity to attribute incentive salience to a
      food cue, a cocaine cue spurred motivation to take drugs (its removal greatly
      diminished self-administration) and reinstated robust drug-seeking after
      extinction. However, in those individuals that failed to attribute incentive
      salience to a food cue, the cocaine cue was relatively devoid of incentive
      motivational properties. CONCLUSIONS: We conclude that it is possible to
      determine, before any drug experience, which individuals will most likely have
      difficulty resisting drug cues, a trait that might confer susceptibility to
      addiction.

PMID- 20045509
TI  - DFTMD studies of glucose and epimers: anomeric ratios, rotamer populations, and
      hydration energies.
AB  - Results are presented from density functional molecular dynamics (DFTMD)
      simulations, based on constant energy dynamics, of glucose and its cyclic form of
      6-carbon epimers. Both in vacuo and an implicit solvent method (COSMO) were
      examined, including simulations of low-energy conformations of each molecule.
      Analysis of the DFTMD results includes the following: energies averaged over the
      simulation time, calculated anomeric ratios, hydroxyl and hydroxymethyl rotamer
      populations, and hydration energies. Hydrogen-bonding networks persistence times
      were examined, and the effects of solvation on rotamer populations were
      described. Anomeric ratios calculated from energy optimization of an ensemble of
      low-energy conformers are compared to those obtained from ensemble averages from
      molecular dynamics, with dynamics simulations giving populations in best
      agreement with experimental anomeric ratios. Ensemble results in vacuo were not
      in agreement with experimental anomeric ratios or hydroxymethyl populations,
      producing in some cases reversal of the alpha:beta ratios. The difficulty in
      obtaining correct alpha:beta ratios increases with the number of axial groups;
      the mono-axial epimers being best represented, epimers with two axial groups
      being more difficult, and the epimers with three axial hydroxyl groups being most
      difficult to analyze, the result of a large number of very strong hydrogen
      bonding networks that form the ensemble of low-energy conformations in the multi
      axial structures.

PMID- 20045510
TI  - Versatile syntheses of mono- or bis-allylhalothiol-carbonates of some alditol or
      sugar derivatives via cyclic thionocarbonates as intermediates.
AB  - We describe herein an extension of the halogenation of 1,2 or 1,3-diols via a
      cyclic thionocarbonate functionality by reaction with an allyl halide instead of
      methyl iodide, which is usually used. This investigation was successfully carried
      out under both conventional heating and microwave solvent-free conditions with
      some alditol, thioanhydroalditol, and aldose derivatives.

PMID- 20045511
TI  - Renaturation of triple helical polysaccharide lentinan in water-diluted
      dimethylsulfoxide solution.
AB  - Triple helical lentinan, a beta-(1-->3)-D-glucan from Lentinus edodes, was
      denatured in dimethylsulfoxide (DMSO) into single random coils. The randomly
      coiled lentinan/DMSO solutions were diluted with pure water to w(H) (the weight
      fraction of water in the mixed solvent) of 95%, and their intrinsic viscosity
      [eta], weight-average molecular weight M(w), radius of gyration R(g), and
      hydrodynamic radius R(h) were investigated at 25 degrees C after over 5-day
      storage. The [eta] and M(w) values, especially the conformation parameter rho
      (identical with R(g)/R(h)), of the renatured lentinan were close to those of the
      originally extracted one, suggesting that random lentinan chains in DMSO were
      reassembled into triple helical structures. Moreover, the renatured lentinan in
      95% water/5% DMSO solution exhibited a unique behavior of triple helical glucans
      that shear modulus G' decreased sharply at temperature from 8.4 degrees C to 13.3
      degrees C with increasing temperature, which was ascribed to the intramolecular
      conformation transition from ordered triple helical I to disordered triple
      helical II. The AFM images gave was suggested intuitively evidence that the
      renatured lentinan mainly existed as rod-like chains, supporting that formation
      of triple helical structure. The optimal lentinan concentration for triple
      helical configuration formation was estimated to be over 0.04%. The time
      dependence of R(h) and UV absorption of the water-diluted lentinan/DMSO solution
      with an indicator of azo dye of Congo red suggested that renaturation of triple
      helix was a very rapid process. Moreover, the blue-shift of UV-vis absorption
      spectra suggested that the dye molecules of Congo red were assembled into
      supramolecular structure in the hydrophobic cavity of the renatured triple
      helical lentinan. All the results showed that the triple helical structure formed
      once the randomly coiled lentinan/DMSO was diluted to the final water content of
      95%.

PMID- 20045512
TI  - Association between GSTO2 polymorphism and the urinary arsenic profile in copper
      industry workers.
AB  - Two members of the recently identified Omega class glutathione S-transferase
      enzymes (GSTO1 and GSTO2) have been proposed to play a role in the response to
      arsenic exposure. Therefore, polymorphisms in these genes could be related with
      variations in the arsenic excretion profile and, consequently, with the
      individual response to chronic exposure. Exons and flanking regions of GSTO2 gene
      have been screened in two different ethnic groups (20 Europeans and 20 Chilean
      Indians), and the urinary arsenic patterns and the GSTO2 Asn142Asp polymorphism
      have been investigated in 207 copper mine workers occupationally exposed to
      arsenic. Three polymorphisms of GSTO2 already described were detected in
      Europeans and Chilean Indians, although with significant different allele
      frequencies. The genotyping for the Asn142Asp polymorphism revealed that almost
      no significant association exists between this change and the arsenic excretion
      profile. However, 142Asp change seems to be correlated with an increase in DMA
      excretion after age and total urinary arsenic adjustment (OR=3.61; P=0.05).
      Altogether, our findings indicate that ethnical differences should be taken into
      account for correlation studies between GST Omega polymorphisms and arsenic
      susceptibility, and that the 142Asp allozyme could modulate arsenic
      biotransformation and thereby arsenic toxicity.

PMID- 20045513
TI  - Exclusive nodal recurrence after treatment of degenerated parietal endometriosis.
AB  - OBJECTIVE: To report a case of endometriosis degenerated into clear cell
      carcinoma with positron-emission tomography (PET) scan staging. DESIGN: Case
      report. SETTING: University hospital. PATIENT(S): A 43-year-old woman diagnosed
      with endometriosis degenerated into clear cell carcinoma with nodal metastasis at
      the initial diagnosis and exclusive nodal recurrence 6 months after surgery.
      INTERVENTION(S): Resection of the mass with partial resection of the pubic
      symphysis and bilateral external iliac lymphadenectomy. Forty-five days later,
      hysterectomy with bilateral adnexectomy and then adjuvant chemotherapy and
      abdominal-pelvic radiotherapy. MAIN OUTCOME MEASURE(S): The PET scan showed
      positive lymph nodes in the cervical, supraclavicular, bilateral axillary,
      bilateral inguinal, and lumbar-aortic regions. RESULT(S): The patient experienced
      a tumor recurrence after 6 months. After surgical management, she was scheduled
      to receive six cycles of rescue chemotherapy. She died 22 months after the
      initial diagnosis. CONCLUSION(S): The use of PET scan could allow better staging
      at the initial diagnosis and improve follow-up in such patients. The treatment of
      this entity is based on radical surgery associated with adjuvant chemotherapy and
      radiotherapy, but the results are not satisfactory.

PMID- 20045514
TI  - Use of uterine vessel occlusion in the management of uterine myomas: two
      different approaches.
AB  - OBJECTIVE: To evaluate the difference between uterine artery occlusion alone
      (UAO) and combined (UVO) with simultaneous blockage of anastomosis between the
      uterine and ovarian vessels in the management of women with myomas in a 3-year
      follow-up. DESIGN: Case-control study. SETTING: University-associated hospital.
      PATIENT(S): One hundred ten patients with uterine fibroids. INTERVENTION(S):
      Forty-four patients underwent UAO and 66 patients UVO; patients were matched
      using a statistically generated selection of all UVOs performed during the same
      period. MAIN OUTCOME MEASURE(S): Outcomes were assessed by comparing surgical
      parameters, immediate postoperative recovery, and therapeutic outcomes.
      RESULT(S): During the 3-year follow-up, the majority of patients in both groups
      reported symptom relief (ranging from 61.5% to 84.6% in the UVO group and 31.6%
      to 77.3% in the UAO group, on the basis of different kinds of symptoms). However,
      symptom control seemed to be different between the two groups when the follow-up
      time was prolonged; for example, symptom control was better in the UVO group at
      the end of 3 years, especially for menorrhagia (76.5% vs. 34.5%). The fibroid
      size was smaller in the UVO group, resulting in a lower reintervention rate,
      compared with the UAO group (13.6% vs. 36.4%). CONCLUSION(S): If UVO is used for
      uterine fibroids, the 3-year efficacy might be better than that with UAO. This
      finding is worthy of further investigation.

PMID- 20045515
TI  - Antiproliferative effects of anastrozole, methotrexate, and 5-fluorouracil on
      endometriosis in vitro and in vivo.
AB  - OBJECTIVE: To investigate the effects of antiproliferative drugs (anastrozole,
      methotrexate, and 5-fluorouracil [5-FU]) on the proliferation of endometriotic
      cells in vitro and in vivo. DESIGN: Ex vivo study on human endometrial and
      endometriotic cells in culture; establishment of a murine model using mice
      implanted with human endometriosis. SETTING: University research center.
      PATIENT(S): Ten patients with ovarian endometrioma, 10 patients with deep
      infiltrating endometriosis, and 10 patients without endometriosis.
      INTERVENTION(S): Stromal and epithelial cells were extracted from endometrial and
      endometriotic biopsies from patients with endometriosis and from patients without
      endometriosis. Cells were treated in vitro with anastrozole, methotrexate,
      progesterone, or 5-FU. Human endometriotic lesions were implanted in nude mice.
      Mice were treated with 5-FU or phosphate-buffered saline during 4 weeks before
      sacrifice and extraction of the endometriotic implants. MAIN OUTCOME MEASURE(S):
      Stromal and epithelial cell proliferation and pathology score of endometriotic
      implants. RESULT(S): Although anastrozole, methotrexate, and progesterone were
      ineffective, 5-FU significantly decreased the proliferation of endometriotic
      cells in vitro and controlled the growth of both cells from ovarian endometrioma
      and deep infiltrating endometriosis. CONCLUSION(S): Considering common features
      between endometriotic cells and tumor cells, the use of 5-FU could be an option
      in the management of severe endometriosis.

PMID- 20045516
TI  - Identification biomarkers of eutopic endometrium in endometriosis using
      artificial neural networks and protein fingerprinting.
AB  - Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      (SELDI-TOF-MS) protein chip array technology was used to detect biomarkers of
      eutopic endometrium in endometriosis patients. Five potential biomarkers (6,898
      m/z, 5,891 m/z, 5,385 m/z, 6,448 m/z, and 5,425 m/z) were found.

PMID- 20045517
TI  - Absence of insulin resistance and low-grade inflammation despite early metabolic
      syndrome manifestations in children born after in vitro fertilization.
AB  - OBJECTIVE: To investigate the metabolic profile, traditional adipokines, and
      indices of insulin resistance and low-grade inflammation in children born as a
      result of IVF compared with spontaneously conceived controls. DESIGN: Cross
      sectional, case-control study. SETTING: IVF Section of the First Department of
      Obstetrics and Gynecology and the First Department of Pediatrics of the
      University of Athens. PATIENT(S): One hundred six children conceived after
      classic IVF and 68 age-matched spontaneously conceived controls, aged 4-14 years.
      INTERVENTION(S): Children underwent physical examination and morning fasting
      samples were collected. MAIN OUTCOME MEASURE(S): Lipid profile, circulating
      fasting glucose, insulin, leptin, adiponectin, high-sensitivity interleukin-6,
      and high-sensitivity C-reactive protein were determined and the fasting glucose
      to-insulin ratio was calculated. RESULT(S): Children born as a result of classic
      IVF had significantly higher systolic and diastolic blood pressures (BP) and
      triglycerides than controls. These BP differences remained significant even after
      correction for birth size and multiple births. No significant differences in
      biochemical indices of insulin resistance, circulating adipokines, and
      inflammatory markers were detected before or after these same corrections.
      CONCLUSION(S): Despite an increase of BP, children born as a result of IVF have
      no biochemical evidence of insulin resistance, including fasting glucose-to
      insulin ratio and circulating adipokines, or low-grade chronic inflammation.
      However, the long-term impact of periconceptual manipulations should be closely
      monitored.

PMID- 20045518
TI  - Phosphatase of regenerating liver-3: a novel and promising marker in human
      endometriosis.
AB  - OBJECTIVE: To investigate the expression of phosphatase of regenerating liver-3
      (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship
      with endometriosis. DESIGN: A clinical retrospective and molecular study.
      SETTING: Department of obstetrics, gynecology, and reproductive medicine.
      PATIENT(S): One hundred and five women with histopathologically confirmed
      endometriosis, and 50 women with histopathologically assessed normal endometria.
      INTERVENTION(S): Immunohistochemical staining and Western blot analysis. MAIN
      OUTCOME MEASURE(S): Expression of PRL-3 protein. RESULT(S): As shown by the
      immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and
      membrane. The cells that tested positive for PRL-3 were detected in endometriotic
      tissues that did not occur in eutopic and normal endometria. Statistical analysis
      indicated that the expression of PRL-3 was closely associated with the clinical
      stages and recurrence of endometriosis. CONCLUSION(S): Expression of PRL-3 is
      related to the clinical stages and recurrence of endometriosis, which provides
      use with a novel marker and promising target in the treatment of human
      endometriosis.

PMID- 20045519
TI  - Antral follicle count as a predictor of hyperresponse in controlled ovarian
      hyperstimulation/intrauterine insemination in unexplained sterility.
AB  - In this prospective study of women with unexplained infertility undergoing the
      first cycle of controlled ovarian hyperstimulation/intrauterine insemination, the
      presence of 16 or more antral follicles on day 3 of the cycle was a good
      predictor of cancellation due to hyperresponse.

PMID- 20045520
TI  - Attenuated oocyte fertilization and embryo development associated with altered
      growth factor/signal transduction induced by endometriotic peritoneal fluid.
AB  - OBJECTIVE: To investigate whether the embryotoxic effect of peritoneal fluid (PF)
      from infertile women with mild endometriosis on mouse oocytes and embryos is
      associated with changes in embryonic epidermal growth factor (EGF), insulin-like
      growth factor-I (IGF-I), and their receptors. DESIGN: Experimental animal study.
      SETTING: University-based research laboratory. ANIMAL(S): Adult ICR mice.
      INTERVENTION(S): Peritoneal fluid was obtained from fertile women with no
      endometriosis (PF-NE) and infertile women with mild endometriosis (PF-E). In
      vitro fertilization was performed, and mouse two-cell stage embryos were cultured
      in human tubal fluid medium with or without PF. MAIN OUTCOME MEASURE(S): Rates of
      fertilization, cleavage, and blastulation. The embryonic EGF and IGF-I levels in
      culture medium were analyzed by enzyme-linked immunosorbent assay, and EGF
      receptor, IGF-I receptor, and phosphorylated extracellular signal-regulated
      protein kinases (p-ERK) expression was determined by immunofluorescence and
      confocal microscopy. RESULT(S): When oocytes and embryos were cultured in media
      with PF-E, the fertilization capability of oocytes and the development potential
      of embryos were decreased. The levels of embryonic EGF, IGF-I, and their
      receptors were increased. However, p-ERK of the postreceptor signal transduction
      pathway was down-regulated. CONCLUSION(S): Endometriotic PF may attenuate oocyte
      and embryo development by impairing embryonic growth factor/receptor/signal
      transduction, resulting in endometriotic infertility.

PMID- 20045521
TI  - The effect of feed composition on the behavior of chemically selective
      displacement systems.
AB  - In this paper we examine whether adding a more retained protein to the feed will
      mitigate displacer-protein interactions in the column, thus affecting the
      displacement modality that occurs (chemically selective vs. traditional
      displacement chromatography). STD-NMR experiments were carried out to probe
      displacer-protein interactions for the chemically selective displacer chloroquine
      diphosphate and the results indicated that this displacer only had measurable
      interactions with the protein alpha-chymotrypsinogen A. For a two component feed
      mixture containing ribonuclease A and alpha-chymotrypsinogen A, the separation
      resulted in the displacement of ribonuclease A, with the more hydrophobic alpha
      chymotrypsinogen A remaining on the column. On the other hand, when the
      experiment was repeated with cytochrome c added to the feed, all three feed
      proteins were displaced. Column simulations indicated that the combination of
      sample self-displacement occurring during the introduction of the feed, along
      with the dynamics of the initial displacement process at the column inlet was
      responsible for this behavior. These results indicate that for this class of
      hydrophobic-based selective displacers, in order for the protein to be
      selectively retained, the protein should be the most strongly retained feed
      component.

PMID- 20045522
TI  - Study of molecular arrangement of organized molecular films of charge-transfer
      complexes containing 1,3-dithiole-2-thione-4,5-dithiolate by in-plane and out-of
      plane X-ray diffractions.
AB  - We investigated the molecular arrangement and surface morphology of organized
      molecular films of alkylammonium-M bis(1,3-dithiole-2-thione-4,5-dithiolate)
      ((dmit)(2), M = Ni, Au, and Pd) charge-transfer complexes using the surface
      pressure-area (pi-A) isotherm, polarized visible spectroscopy, in-plane and out
      of-plane X-ray diffractions (XRD), and atomic force microscopy (AFM). Since
      Langmuir-Blodgett films of alkylammonium-M(dmit)(2) generally exhibit
      superconductivity, it may be possible to develop novel electronic molecular
      devices on the subnanometer scale. In the bulk state, several alkylammonium
      M(dmit)(2) molecules could not form a highly ordered layered structure along the
      c-axis and a subcell structure of the alkyl chain in the ab-plane; however,
      almost all molecules formed a layered structure in the film multilayers.
      Monolayers of alkylammonium-M(dmit)(2) molecules on the water surface were
      extremely condensed. Out-of-plane and in-plane XRD measurements revealed that
      over a long period, systematic changes occurred in the two-dimensional lattice
      structure of alkylammonium-M(dmit)(2) molecules and not in their bulk state.
      These structural changes appear to be caused by enhancement of the van der Waals
      interaction among long hydrocarbons and the pi-pi interaction among (dmit)(2)
      units arranged two dimensionally. In addition, both the molecular arrangement and
      the structural morphology of the films showed dependence on the hydrocarbon chain
      length, number of long alkyl chains, and kind of central metal. In particular,
      the molecular arrangement of materials having didecyl chains changed drastically
      and (dmit)(2) units were highly oriented in the ab-plane. Such structural
      formations are suggested to significantly influence the stacking of functional
      dmit units presiding over the conductive properties.

PMID- 20045523
TI  - Effect of water chemistry on calcium carbonate deposition on metal and polymer
      surfaces.
AB  - The formation of calcium carbonate on the surfaces of polypropylene and copper
      tubes was studied by exposing tubes to a laminar flow of room temperature
      distilled water, supersaturated with respect to calcite. Three water chemistries
      were used: a control (pH 9.3), one with lower supersaturation but similar pH as
      the control, and one with higher pH (pH 11) but similar supersaturation as the
      control. The accumulation of calcium carbonate with time was characterized along
      with the microstructure and the crystal structure of the deposits. On both tube
      materials, the amount of calcium carbonate deposited per unit surface area
      increased with time. At any given time, the accumulation was significantly less
      when the low supersaturation water was used. For all three water chemistries,
      more calcium carbonate formed on polyproplyene as compared with copper, with the
      greatest difference between the two noted for the higher pH water. The deposits
      consisted of discrete particles and particle clusters, the number and size of
      which increased with time. Calcite was the dominant polymorph for deposits on
      copper. On polyproplyene, the deposits were a mixture of calcite, vaterite and
      aragonite with aragonite dominating except at low supersaturation. A simple model
      for the mass accumulation of particulate-based deposits with time is presented
      and the factors responsible for the differences between materials are discussed.

PMID- 20045524
TI  - Novel layer-by-layer assembly molecularly imprinted sol-gel sensor for selective
      recognition of clindamycin based on Au electrode decorated by multi-wall carbon
      nanotube.
AB  - A novel sensitive molecularly imprinted electrochemical sensor was constructed
      for selective detection of clindamycin by combination of a multi-wall carbon
      nanotube (MWNT) layer with a thin molecularly imprinted sol-gel film. The sensor
      was fabricated onto Au electrode via stepwise modification of MWNT and a thin sol
      gel film of molecularly imprinted polymers (MIP) by using electrodeposition
      method. The molecularly imprinted film displayed excellent selectivity towards
      clindamycin. Due to such combination, the sensor responded quickly to
      clindamycin. The response peak current was linear to the concentration of
      clindamycin in the range from 5.0 x 10(-7) mol L(-1) to 8.0 x 10(-5) mol L(-1),
      and the detection limit was 2.44 x 10(-8) mol L(-1). This imprinted sensor was
      applied to the determination of clindamycin in human urine samples successfully.
      These results revealed that the imprinted sensor fulfilled the selectivity,
      sensitivity, speed and simplicity requirements for clindamycin detection, and
      provided possibilities of clinical application in physiological fluids.

PMID- 20045525
TI  - Nanostructured multilayer TiO2-Ge films with quantum confinement effects for
      photovoltaic applications.
AB  - Multilayer TiO(2)-Ge thin films have been deposited using electron beam
      evaporation and resistive heating. The thickness of the TiO(2) layers is 20 nm,
      while the thickness of the Ge layers varies from 2 to 20 nm with a step of 2 nm
      away from the substrate. These films were characterized by studying their
      optical, electrical, and structural properties. The films were annealed at
      various temperatures up to 500 degrees C for 2 h. The films are amorphous up to
      an annealing temperature of 400 degrees C, although Raman spectra suggest short
      range ordering (and adjustments). The films annealed at 450 and 500 degrees C
      exhibit X-ray reflections of Ge and anatase TiO(2). Illumination in sunlight
      increases the conductivity of the as-deposited and annealed films. The band gap
      of the amorphous films changes from 1.27 to 1.41 eV up to 400 degrees C; the
      major contribution is possibly through direct transition. Two band gap regimes
      are clearly seen after 450 and 500 degrees C, which have been assigned to an
      indirect band gap at about 1.2 eV and a direct band gap at about 1.8 eV.
      Conductivity of the multilayer films has been higher than that of pure Ge film.
      The conductivity increases with annealing temperature with abrupt increase at
      about 380 degrees C. The results imply that the TiO(2)-Ge multilayer films may be
      employed as heterojunctions with tunable band gap energy as related to quantum
      confinement effects.

PMID- 20045526
TI  - Adsorption of hazardous dye crystal violet from wastewater by waste materials.
AB  - The adsorption performance of the materials bottom ash (BA), a power plant waste,
      and de-oiled soya (DOS), a soya bean industry waste for removal of crystal violet
      dye, has been investigated through batch and column experiments. Batch studies
      have been performed to describe the impact of parameters such as pH, amount of
      adsorbent, dye concentration, temperature, and contact time on the removal of the
      dye. Experimental data have been modeled by using Langmuir, Freundlich, Tempkin,
      and Dubinin-Radushkevich (D-R) isotherms. Thermodynamic parameters (DeltaG(o),
      DeltaH(o), and DeltaS(o)) were evaluated for the dye-adsorbent systems, which
      revealed that the adsorption process is endothermic in nature. Pseudo-first- and
      second-order kinetic models have been applied to the experimental data and pseudo
      second-order kinetics was found to describe the adsorption of the dye (crystal
      violet) on the adsorbents. In order to achieve bulk removal of the dye, column
      operations were made. Recovery of the dye was made by eluting HCl solution
      through the exhausted columns and almost 95% and 78% of the dye was recovered
      from BA and DOS columns, respectively.

PMID- 20045527
TI  - Size matters: management of stress responses and chronic stress in beaked whales
      and other marine mammals may require larger exclusion zones.
AB  - Marine mammal management traditionally focuses on lethal takes, but non-lethal
      (or not immediately lethal) impacts of human disturbance, such as prolonged or
      repeated activation of the stress response, can also have serious conservation
      implications. The physiological stress response is a life-saving combination of
      systems and events that maximises the ability of an animal to kill or avoid being
      killed. However, "chronic stress" is linked to numerous conditions in humans,
      including coronary disease and infertility. Through examples, including beaked
      whales and sonar exposure, we discuss increasing human disturbance, mal-adaptive
      stress responses and chronic stress. Deep-diving and coastal species, and those
      targeted by whalewatching, may be particularly vulnerable. The various conditions
      linked with chronic stress in humans would have troubling implications for
      conservation efforts in endangered species, demands management attention, and may
      partly explain why some species have not recovered after protective measures
      (e.g., smaller protected areas) have been put into place.

PMID- 20045528
TI  - [Importance of early detection of chronic kidney disease in risk groups].

PMID- 20045529
TI  - [Infective endocarditis: the role of surgery].
AB  - Infective endocarditis (IE) is a serious disease which can carry a bad prognosis
      if it is not appropriately treated. Sometimes the clinical evolution is
      unfavourable despite an optimal medical therapy with antibiotics. Surgery in
      these cases has an important role to eliminate the source of infection or to
      perform a valve replacement. The surprising evolution of patients operated in
      critic circumstances take us to analyze the role of early surgery. As physicians,
      we need to know these patients' risks and to establish the adequate surgical
      indications.

PMID- 20045530
TI  - [Global therapy of diabetic dyslipidemia: benefits and new therapeutic
      approaches].
AB  - Diabetic dyslipidemia, characterized by the lipid triad (elevated plasma
      triglycerides, low HDL cholesterol and predominance of small, dense LDL
      particles), is a significant contributor to the elevated cardiovascular risk of
      type 2 diabetic patients. Statin monotherapy has shown, in different prospective
      trials, significant reductions in cardiovascular events and mortality. However,
      the residual risk in these subjects remains elevated, probably due to the
      incomplete control of diabetic dyslipidemia. In this review we discuss the global
      therapeutic approach, underlying the need of combining statins with agents that
      more effective in reducing triglycerides and elevating HDL cholesterol, even in
      subjects whose LDL cholesterol values are at target. Available data supports that
      such combinations contribute to normalize the lipid profile with possible
      beneficial effects on the cardiovascular risk. Ongoing clinical trials, using
      different combinations and focusing on cardiovascular morbidity and mortality are
      also discussed. In our opinion, the future treatment of diabetic dyslipidemia
      will include the combination of statins and other hypolipidemic agents.

PMID- 20045531
TI  - [Subclinical and established kidney disease in recently diagnosed hypertensive
      patients].
AB  - BACKGROUND AND OBJECTIVE: To estimate renal disease in recently diagnosed
      hypertensive patients, and to identify factors related to renal disease. PATIENTS
      AND METHODS: Cross-sectional study, with 425 hypertensive patients recently
      diagnosed in primary health care; renal disease was estimated with serum
      creatinine, albumin/creatinine index and glomerular filtration rate (GFR). We
      analyzed cardiovascular risk factors (CRF), subclinical organ injury and
      cardiovascular disease following the criteria of the 2007 European Guide of
      Hypertension. RESULTS: Average age: 58,96 +/- 12,73 years old, 63,3% male. We
      found dyslipemia in 80%, abdominal obesity in 49% and metabolic syndrome in 36%
      patients. These patients showed increased serum creatinine 3,3%, a reduction in
      GFR 9,6%, hidden renal disease 6,4%, microalbuminuria 7,5% and nephropathy 2,4%.
      Hypertensive patients with renal disease (17,88%) were older, with higher
      systolic pressure, higher incidence of metabolic syndrome, abnormal carotid
      intima-media thickness and ankle-arm index, and presence of cardiovascular
      disease. Variables associated with renal disease were metabolic syndrome (odds
      ratio = 11,12) and ankle-arm index (odds ratio = 17,55). Variables related to
      creatinina were sex, ankle-arm index and metabolic syndrome; variables related to
      GFR were sex, age, ankle-arm index, metabolic syndrome and body mass index (BMI);
      variables related with albumin/creatinine index included diabetes mellitus.
      CONCLUSIONS: Renal disease is detected in about 2 out of 10 hypertensive
      patients, when, besides serum creatinina, we analyze albumin/creatinine index and
      GFR. Metabolic syndrome and ankle-arm index are the main variables associated
      with renal disease.

PMID- 20045532
TI  - Dysfunctional pancreatic beta-cells of critical stress play a more prominent role
      in the development of stress diabetes in critically burned Korean subjects.
AB  - The purposes of this study are to identify the predictive parameters for the
      development of stress-induced hyperglycemia and to investigate the glucose
      metabolic homeostasis in critically burned Korean subjects. We conducted a
      prospective cross-sectional study of adult patients with glucose management
      targeting fasting and postprandial blood glucose levels less than 140 and 200
      mg/dL, respectively, in patients with unrecognized diabetes. Clinical and
      laboratory stress parameters and insulin secretory and sensitivity parameters
      were assessed. Stimulated C-peptide and 24-hour urinary free cortisol predicted
      new-onset stress diabetes requiring insulin therapy. The subjects requiring
      insulin therapy were leaner and more insulin sensitive than insulin-free
      subjects, without significance. Glycated hemoglobin, stimulated C-peptide,
      homeostasis model assessment of insulin resistance, and age had a significant
      influence on the mean daily dose of insulin. Our present data showed that Korean
      subjects with dysfunctional pancreatic beta-cells of critical stress are prone to
      become stress diabetic and require more insulin to control the hyperglycemia.

PMID- 20045533
TI  - Low birth weight is associated with components of the metabolic syndrome.
AB  - The purpose of the study was to investigate the association between birth weight
      and number of metabolic syndrome (MetS) components in an urban Chinese cohort.
      Individuals (N = 2019) who were born between 1921 and 1954 at the Peking Union
      Medical College Hospital and who had detailed obstetric records volunteered to
      take part and were examined by medical personnel in a clinical setting between
      May 2003 and April 2005. Data of birth outcome and results on clinic examination
      in adulthood were analyzed using analysis of variance and multivariate ordinal
      regression to estimate the association between birth weight and MetS. Metabolic
      syndrome was defined as per the National Cholesterol Education Program Adult
      Treatment Panel III. The prevalence of MetS was 26.74%, whereas 55.43% of the
      subjects had at least 2 components of MetS. Subjects who presented with all 5
      components of MetS exhibited a significantly lower birth weight and higher age,
      body mass index, and waist circumference at follow-up. Multivariate ordinal
      regression analysis revealed that, as compared with those with birth weights of
      3000 to 3500 g, subjects who had birth weights of less than 2500 g were 66% more
      likely to develop a greater number of MetS components in adulthood (95%
      confidence interval, 1.18-2.34; P = .004), whereas those with birth weights
      between 2500 and 3000 g were 33% more likely to develop a greater number of MetS
      components as adults (95% confidence interval, 1.09-1.63; P = .005). The present
      study demonstrated the relationship between low birth weight and increased
      presentation of MetS components in Chinese adults.

PMID- 20045535
TI  - Baseline serum total adiponectin level is positively associated with changes in
      bone mineral density after 1-year treatment of type 2 diabetes mellitus.
AB  - Although recent clinical studies have shown that serum adiponectin level was
      negatively associated with bone mineral density (BMD), serum adiponectin action
      on bone metabolism in humans is still unclear. We investigated the relationships
      between serum levels of total and high-molecular weight (HMW) adiponectin and its
      ratio (HMW-total ratio) vs chronological changes in BMD at the lumbar spine,
      femoral neck (FN), and one third of the radius after 1-year treatment of type 2
      diabetes mellitus in 32 Japanese patients. Serum total adiponectin, but not HMW
      adiponectin or HMW-total ratio, was significantly and positively correlated with
      percentage change in FN-BMD (r = 0.35, P < .05). Multiple regression analysis
      adjusted for age, duration of diabetes, sex, body height, body weight, waist
      circumference, serum creatinine, and hemoglobin A(1c) showed that serum total
      adiponectin was still significantly and positively correlated with percentage
      change in FN-BMD (r = 0.65, P < .01). On the other hand, no significant
      relationships were found between serum levels of hemoglobin A(1c), pentosidine,
      bone formation markers (bone-specific alkaline phosphatase and osteocalcin), or a
      bone resorption marker (urinary N-terminal cross-linked telopeptide of type-I
      collagen) vs percentage change in BMD at any site. These findings suggest that
      serum total adiponectin could be clinically useful for predicting BMD change
      during treatment of type 2 diabetes mellitus. Adiponectin might protect against
      BMD reduction in patients with type 2 diabetes mellitus.

PMID- 20045534
TI  - Metabolic syndrome and risk of death from cancers of the digestive system.
AB  - We tested the hypothesis that risk of early mortality from cancers of the
      digestive system will be greater in men with, compared with men without, the
      metabolic syndrome (MetS). Participants were 33,230 men who were seen at the
      Cooper Clinic in Dallas, TX, and followed for 14.4 (SD = 7.0) years. Metabolic
      syndrome was defined as having at least 3 of the following risk factors:
      abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein
      cholesterol, high blood pressure, or high fasting glucose level or diabetes.
      Metabolic syndrome was associated with higher mortality (hazard ratio [HR] = 1.90
      [95% confidence interval = 1.42-2.55]), and there was a graded positive
      association for the addition of more syndrome components (P < .01). Adjustment
      for cardiorespiratory fitness attenuated the risk estimates by 20% to 30%, but
      they remained significant after this adjustment. Evaluation of the independent
      contribution of each of the syndrome components revealed that both abdominal
      obesity (HR = 1.89 [1.36-2.62]) and high glucose (HR = 1.38 [1.02-1.87]) were
      independently associated with cancer mortality. Our results support the
      hypothesis that metabolic syndrome is positively associated with mortality from
      cancers of the digestive system. Interventions that reduce abnormalities
      associated with the syndrome could reduce risk of premature death from these
      cancers.

PMID- 20045536
TI  - Association between low pulmonary function and metabolic risk factors in Korean
      adults: the Korean National Health and Nutrition Survey.
AB  - Impaired lung function is a risk factor for cardiovascular events and mortality.
      In addition, lung function impairment is also associated with insulin resistance
      and type 2 diabetes mellitus. It is well known that a common mechanism, such as
      insulin resistance and obesity, underlies metabolic syndrome. Our aim was to
      evaluate the association between impaired lung function and metabolic risk
      factors using data from a nationwide survey of chronic obstructive pulmonary
      disease prevalence in Korea and the Korean National Health and Nutrition Survey
      in 2001. The study population included 4001 subjects (aged > or =18 years) who
      underwent spirometry at least twice. We analyzed the association of low pulmonary
      function with metabolic syndrome components using multiple linear regression and
      also analyzed the association of metabolic syndrome with restrictive lung disease
      and obstructive lung disease using multiple logistic regression adjusted for
      waist to height ratio, sex, age, smoking, and the other covariates. Waist girth,
      systolic blood pressure, and triglyceride were associated with forced vital
      capacity (FVC); and only triglyceride was so with forced expiratory volume in 1
      second (FEV(1)), but not with FEV(1)/FVC ratio. The odds ratio of metabolic
      syndrome for restrictive lung disease (FVC <80%, FEV(1)/FVC >0.7) was 1.40 (95%
      confidence interval, 1.01-1.98), and that for obstructive lung disease
      (FEV(1)/FVC <0.7) was 0.93 (95% confidence interval, 0.67-1.28) after adjustment
      for covariates. These results indicate that low pulmonary function in the general
      population is associated with clustering of metabolic syndrome risk factors and,
      furthermore, that restrictive lung disease is also related to metabolic syndrome.

PMID- 20045537
TI  - Two unhealthy dietary habits featuring a high fat content and a sucrose
      containing beverage intake, alone or in combination, on inducing metabolic
      syndrome in Wistar rats and C57BL/6J mice.
AB  - To establish animal models with diet-induced metabolic disorders similar to human
      metabolic syndrome, 2 unhealthy dietary habits featuring a high fat content and a
      sucrose-containing beverage intake, alone or in combination, were tested on
      Wistar rats and C57BL/6J mice. The 2 dietary habits were, respectively, simulated
      by feeding a high-fat diet (regimen A) or additionally providing 30% sucrose
      (wt/vol) in the drinking water (regimen B). Using a 2 x 2 factorial design, 4
      groups of animals were fed chow diet plus plain water (group C), high-fat diet
      (30% [wt/wt] fat) plus plain water (group A), chow diet plus sucrose in drinking
      water (group B), and high-fat diet plus sucrose in drinking water (group AB) for
      26 weeks. In Wistar rats, regimen B caused a significant increase in visceral
      fat; serum levels of lipids, glucose, insulin, and uric acid; insulin resistance;
      and blood pressure, whereas regimen A only caused a significant increase in
      visceral fat and serum insulin levels (P < .05). In contrast, regimen A induced a
      full array of metabolic syndrome in C57BL/6J mice; but regimen B only caused
      slight obesity and hyperlipidemia. In both Wistar rats and C57BL/6J mice, there
      were no additive effects of the 2 regimens, indicated by significant interactions
      between regimens A and B on the metabolic indexes measured. These results show
      that, in terms of inducing metabolic syndrome, Wistar rats are more responsive to
      sucrose water regimen, whereas C57BL/6J mice are more responsive to the high-fat
      diet regimen.

PMID- 20045538
TI  - Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in
      obesity.
AB  - Adipose tissue expresses all components of the renin-angiotensin system including
      angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in
      adipose tissue function and homeostasis. However, some controversies surround the
      regulatory mechanisms of AGT in obese adipose tissue. In this context, we here
      demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous
      adipose tissue was significantly reduced in obese subjects as compared with
      nonobese subjects. Adipose tissue AGT mRNA level in obese mice was also lower as
      compared with their lean littermates; however, the hepatic AGT mRNA level
      remained unchanged. When 3T3-L1 adipocytes were cultured for a long period, the
      adipocytes became hypertrophic with a marked increase in the production of
      reactive oxygen species. Expression and secretion of AGT continued to decrease
      during the course of adipocyte hypertrophy. Treatment of the 3T3-L1 and primary
      adipocytes with reactive oxygen species (hydrogen peroxide) or tumor necrosis
      factor alpha caused a significant decrease in the expression and secretion of
      AGT. On the other hand, treatment with the antioxidant N-acetyl cysteine
      suppressed the decrease in the expression and secretion of AGT in the
      hypertrophied 3T3-L1 adipocytes. Finally, treatment of obese db/db mice with N
      acetyl cysteine augmented the expression of AGT in the adipose tissue, but not in
      the liver. The present study demonstrates for the first time that oxidative
      stress dysregulates AGT in obese adipose tissue, providing a novel insight into
      the adipose tissue-specific interaction between the regulation of AGT and
      oxidative stress in the pathophysiology of obesity.

PMID- 20045539
TI  - Hepatic mitochondrial energetics during catch-up fat after caloric restriction.
AB  - The objective of the study was to investigate whether changes in liver
      mitochondrial energetics could underlie the enhanced energetic efficiency that
      drives accelerated body fat recovery (catch-up fat) during refeeding after
      caloric restriction. Rats were subjected to caloric restriction (50% of ad
      libitum intake) for 15 days and then refed for 1 or 2 weeks on an amount of chow
      equal to that of controls matched for weight at the onset of refeeding. Whole
      body metabolism was characterized by energy balance and body composition
      determinations as well as by indirect calorimetric measurements of 24-hour energy
      expenditure, substrate oxidation, and whole-body de novo lipogenesis estimated
      from nonprotein respiratory quotient. Hepatic mitochondrial energetics were
      determined from measurements of liver mitochondrial mass, respiratory capacities,
      and proton leak (both basal and fatty acid stimulated), whereas hepatic oxidative
      status was assessed from measurements of hepatic mitochondrial lipid
      peroxidation, aconitase, and superoxide dismutase activity. Furthermore, hepatic
      lipogenic capacity was determined from assays of fatty acid synthase activity.
      Compared with controls, isocalorically refed rats showed an elevated energetic
      efficiency and body fat gain over both week 1 and week 2 of refeeding, as well as
      a lower 24-hour energy expenditure and higher rates of whole-body de novo
      lipogenesis at the end of both week 1 and week 2 of refeeding. Analysis of the
      liver revealed that after 1 week (but not after 2 weeks) of refeeding, the
      mitochondrial mass (but not mitochondrial density) was lower in refed rats than
      in controls, associated with higher state 3 mitochondrial respiratory capacity,
      increased superoxide dismutase activity, as well as higher fatty acid synthase
      activity. These results suggest that, although at the whole-body level elevations
      in energy efficiency and de novo lipogenesis are coordinated toward catch-up fat,
      the overall hepatic mitochondrial energetic status during refeeding is more
      consistent with a contributory role of the liver in the enhanced de novo
      lipogenic machinery during catch-up fat rather than in the energy-conservation
      mechanisms (elevated energetic efficiency) that spare energy for catch-up fat.

PMID- 20045540
TI  - Protective effect of caffeic acid on cardiac markers and lipid peroxide
      metabolism in cardiotoxic rats: an in vivo and in vitro study.
AB  - Myocardial infarction affects a large population in the world. Lipid peroxide
      metabolism plays an important role in the pathology of myocardial infarction.
      This study aims to evaluate the preventive effect of caffeic acid on lipid
      peroxides, antioxidants, cardiac marker enzymes, and histopathological findings
      in isoproterenol (ISO)-induced myocardial-infarcted male Wistar rats. Myocardial
      infarction was induced in rats by subcutaneous injection of ISO (100 mg/kg) at an
      interval of 24 hours for 2 days. The ISO-induced rats showed significant increase
      in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides in
      the heart, plasma uric acid, and serum cardiac marker enzymes, and significant
      decrease in the activities of heart superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase, glutathione-S-transferase, and the levels of
      reduced glutathione, vitamin E, and vitamin C in the plasma and heart. Oral
      pretreatment with caffeic acid (15 mg/kg) daily for 10 days showed significant
      decrease in the levels of serum cardiac marker enzymes, heart lipid peroxidation
      products and plasma uric acid and significant increase in the levels of
      antioxidant system. Histopathology of myocardium also confirmed the protective
      effect of caffeic acid in myocardial-infarcted rats. In vitro study on total
      antioxidant activity (2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid](+)
      assay) confirmed the strong antioxidant action of caffeic acid. Thus, the present
      study revealed that caffeic acid ameliorates cardiac damage in ISO-induced
      myocardial infarction by maintaining lipid peroxide metabolism due to its free
      radical scavenging and antioxidant effects. A diet containing caffeic acid may be
      beneficial to myocardial infarction.

PMID- 20045541
TI  - High follicular fluid adenosine levels may be pivotal in the metabolism and
      recycling of adenosine nucleotides in the human follicle.
AB  - This study investigated the biochemical relationship between human
      follicular/oocyte maturity and the levels of follicular fluid purines.
      Intrafollicular levels of purine metabolites and creatinine are associated with
      oocyte presence, and the presence of such high levels of adenosine indicates a
      privileged site with no adenosine deaminase activity. Subgrouping according to
      oocyte recovery and fertilization revealed differences in correlation between the
      purine metabolites: Only where an oocyte was recovered and subsequently
      fertilized did follicular fluid adenosine, adenine, and hypoxanthine levels
      correlate with each other. Significantly, purines' correlation with levels of the
      terminal degradation product, uric acid, could only be seen in failed
      fertilization samples. Given the established metabolic pathways for adenosine
      triphosphate/adenosine diphosphate/adenosine monophosphate degradation, the
      results indicate maximization of 2 purine salvage pathways (from adenine and
      hypoxanthine) that pivot on the presence of high adenosine levels. Such optimized
      recovery may be necessary to build a store of salvaged adenosine phosphate for
      oocyte survival.

PMID- 20045542
TI  - Serum enzyme status of Chios ewes fed increasing amounts of copper from copper
      sulfate.
AB  - This study aimed to evaluate effects of orally administered copper (Cu) to Chios
      sheep breed on serum levels of aspartate aminotransferase (AST), l-alanine
      aminotransferase (ALT), lactate deydrogenase (LDH) and alkaline phosphatase
      (ALP), in order to establish a practical and effective method in diagnosing the
      prehemolytic stage of chronic Cu poisoning. Eighteen ewes were allocated to three
      treatments of six ewes and fed a diet that contained 16.4 mg/day of Cu. Ewes in
      treatment Cu-0 received no additional Cu (control), while those in treatments Cu
      60 and Cu-95 received 60 and 95 mg additional Cu/day, respectively, as an oral
      solution of copper sulfate. Therefore the ewes in treatment Cu-0, Cu-60 and Cu-95
      consumed 16.4, 76.4 and 111.4 mg Cu/day, respectively. Serum enzyme levels were
      similar among treatments and all ewes remained clinically healthy until the end
      of the experiment. Results suggest that Chios ewes exhibit tolerance to Cu
      supplementation for up to 6 weeks.

PMID- 20045543
TI  - Effects of isoniazid and niacin on experimental wound-healing.
AB  - BACKGROUND: There is a need for effective treatments of ischemic wounds. Our aim
      was to test the hypothesis that systemic administration of isoniazid or niacin
      can enhance wound healing in ischemic as well as nonischemic tissues. METHODS:
      One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and
      1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting
      just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.),
      xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days.
      Wound-healing was monitored by planimetry and oxygen tension in periphery of the
      wound using a microcatheter probe. Cellular proliferation in granulation tissue
      was assessed by immunohistochemical detection of proliferating cell nuclear
      antigen. The angiogenic activity of isoniazid and niacin was assessed using in
      vitro and ex vivo models. RESULTS: Although wound ischemia was evident by
      decreased oxygen tension (26 +/- 10 mmHg; n = 9) compared with the adjacent
      nonischemic wounds (51 +/- 8 mmHg; n = 8), neither compound significantly
      influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin,
      promoted ischemic wound-healing even though both compounds increased
      proliferation measured on day 14 (P < .01). In normal wounds, the cumulative
      change in relative wound area over 14 days was increased by niacin (P = .002),
      but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036)
      increased cellular proliferation. Neither isoniazid nor niacin showed activity in
      either an endothelial tube formation assay or organotypic angiogenic assay under
      normoxic conditions. CONCLUSION: Isoniazid was capable of stimulating wound
      healing in ischemic tissue to the level of nonischemic wounds and might offer a
      novel treatment option for wounds associated with arterial insufficiency.
      Although active in normal wounds, niacin did not promote ischemic wound-healing.

PMID- 20045544
TI  - Bone scan demonstration of osteoblastic tumor of the breast.

PMID- 20045545
TI  - Technologic developments in telemedicine: state-of-the-art academic interactions.

PMID- 20045546
TI  - Overt diabetes mellitus adversely affects surgical outcomes of noncardiovascular
      patients.
AB  - BACKGROUND: It is known that cardiac surgical patients with diabetes have greater
      peri-operative mortality and morbidity when compared with nondiabetic patients;
      the rate of adverse events in other surgery subspecialties has been only
      investigated minimally. The aim of this study was to test the magnitude of
      association between overt diabetes mellitus and postoperative complications
      across a spectrum of noncardiac surgical patients. METHODS: Prospective outcome
      data registries describing 1,343 data sets from a spectrum of surgical
      subspecialties were examined to establish the prevalence of diagnosed diabetes,
      the incidence of intra- and postoperative complications, and the difference in
      proportion of morbidity between diabetic versus nondiabetic patients. RESULTS:
      There was a significant difference in overall morbidity between diabetic and
      nondiabetic patients with a 2.0 and 1.6 times increased morbidity risk in known
      diabetic patients with and without malignancy, respectively. Known diabetes was
      related to the number of postoperative complications in noncardiovascular
      patients. CONCLUSION: This study quantified the association between known
      diabetes and the occurrence of complications during recovery after a spectrum of
      noncardiac surgery. Because of a high prevalence of prediabetic and undiagnosed
      conditions, the strength of associations between glucose dysregulation and
      operative outcomes may be even greater than we report.

PMID- 20045547
TI  - Influence of alternating oxic/anoxic conditions on growth of denitrifying
      bacteria.
AB  - Denitrifying bacteria that are switched from oxic to anoxic conditions can
      experience diauxic lag, which is the time required for re-synthesis of nitrate
      reductase and other denitrifying enzymes. Pseudomonas denitrificans were exposed
      to alternating oxic/anoxic phases in a continuous flow reactor with either 4-h or
      8-h anoxic phase lengths, in comparison to a measured diauxic lag of 9.5h
      following steady-state oxic conditions. The P. denitrificans were unable to
      sustain anoxic growth at either of the anoxic phase lengths tested. Diauxic lag
      observed after several cycles of alternating oxic/anoxic phases was significantly
      longer than the diauxic lag measured after steady-state oxic conditions. This may
      be attributed to increase of cell maintenance energy requirements due to
      substrate accumulation during anoxic phases and concomitant high specific growth
      rates during oxic phases.

PMID- 20045549
TI  - Sorption of quaternary ammonium compounds to municipal sludge.
AB  - The sorptive behavior of four quaternary ammonium compounds (QACs) - hexadecyl
      trimethyl ammonium chloride (C(16)TMA), dodecyl trimethyl ammonium chloride
      (C(12)TMA), hexadecyl benzyl dimethyl ammonium chloride (C(16)BDMA), and dodecyl
      benzyl dimethyl ammonium chloride (C(12)BDMA) - to municipal primary, waste
      activated, mesophilic digested, and thermophilic digested sludges was assessed at
      22 degrees C. Batch adsorption of all four separately tested QACs to primary
      sludge reached equilibrium within 4h. At a nominal, initial QAC concentration of
      300mg/L and a sludge volatile solids concentration of 1g/L, the extent of
      adsorption was 13, 88, 67, and 89% for the C(12)TMA, C(16)TMA, C(12)BDMA, and
      C(16)BDMA, respectively, and correlated positively to the QAC hydrophobicity and
      negatively to their critical micelle concentration. Equilibrium partitioning data
      were described by the Freundlich isotherm model. The adsorption capacity of the
      four sludges was very similar. In binary QAC mixtures, QACs with relatively high
      adsorption affinity and at relatively high aqueous concentrations decreased the
      adsorption of QACs with a low adsorption affinity. At pH 7, about 40% of the
      sludge-C(12)TMA desorbed, whereas less than 5% of the sludge-C(16)BDMA desorbed
      in 10 days. The effect of pH was negligible on the desorption extent of C(12)TMA
      at a pH range 4-10 over 10 days, whereas increasing the solution pH to 10
      resulted in more than 50% desorption of C(16)BDMA. Given the fact that
      approximately 50% of the municipal biosolids are land-applied in the US, the data
      of this study would help in the assessment of the fate of QACs and their
      potential effect on human and environmental health.

PMID- 20045548
TI  - Effects of natural organic matter model compounds on the transformation of carbon
      tetrachloride by chloride green rust.
AB  - Interest has grown in the use of reactive minerals for natural and engineered
      transformation of ground water contaminants. This study investigated how the
      structural properties of 10 model compounds representing natural organic matter
      (NOM) influenced their adsorption to chloride green rust (GR-Cl), and how this
      adsorption affected rate constants for transformation of carbon tetrachloride
      (CT) by GR-Cl. The affinity of benzoic acid, phthalic acid, trimesic acid,
      pyromellitic acid, and mellitic acid for the GR-Cl surface generally increased in
      the order of increasing number of carboxylic acid functional groups, increasing
      acidity of these functional groups, and increasing charge density. For NOM model
      compounds that had phenolic functional groups (p-hydroxybenzoic acid, alpha
      resorcylic acid, and caffeic acid), the affinity for the GR-Cl surface was
      greatest for caffeic acid, which had two adjacent phenolic functional groups.
      Some NOM model compounds had experimentally determined Langmuir maximum
      adsorption capacities (q(max-Langmuir)) greater than those calculated based on
      external surface area measurements and the size of the NOM model compound,
      suggesting adsorption to internal as well as external sites at the GR-Cl surface
      for these compounds. Rate constants for CT transformation by GR-Cl generally
      decreased as the affinity of the NOM model compounds (estimated by Langmuir K
      values) increased, but there was no statistically significant correlation between
      Langmuir parameters (i.e., K and q(max-Langmuir)) and rate constants, perhaps due
      to significant adsorption of some NOM model compounds to sites that were not
      accessible to CT, such as interlayer sites. Unlike the other NOM model compounds,
      caffeic acid, which adsorbed to a significant extent to the GR-Cl surface,
      increased the rate constant for CT transformation. The influence of NOM on rate
      constants for CT transformation by green rusts should be considered in ground
      water remediation planning.

PMID- 20045550
TI  - An effective pathway for the removal of microcystin LR via anoxic biodegradation
      in lake sediments.
AB  - Aerobic biodegradation has been considered to be the main attenuation mechanism
      for microcystins, but the role of anoxic biodegradation remains unclear. We
      investigated the potential for anoxic biodegradation of microcystin and the
      effects of environmental factors on the process through a series of well
      controlled microcosm experiments using lake sediments as inocula. Microcystin LR
      could be degraded anoxically from 5mgL(-1) to below the detection limit at 25
      degrees C within 2 days after a lag phase of 2 days. The rate was highly
      dependent on temperature, with a favorable temperature range of 20-30 degrees C.
      The addition of glucose or low levels of NH(4)-N had no effect on the anoxic
      biodegradation of microcystin, whereas the addition of NO(3)-N significantly
      inhibited the biodegradation at all experimental concentrations, and the
      inhibition increased with increasing amount of NO(3)-N-amended. Adda (3-amino-9
      methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid), a previously reported
      nontoxic product of aerobic degradation of microcystin, was identified as the
      anoxic biodegradation product. This is the first report of Adda as a degradation
      product of microcystin under anoxic conditions. No other product containing Adda
      residue was detected during the anoxic degradation of microcystin. These results
      strongly indicated that anoxic biodegradation is an effective removal pathway of
      microcystin in lake sediments, and represents a significant bioremediation
      potential.

PMID- 20045551
TI  - Chemical contaminants in aquafeeds and Atlantic salmon (Salmo salar) following
      the use of traditional- versus alternative feed ingredients.
AB  - Marine feed ingredients, traditionally used in commercial fish feeds, are the
      source of these pollutants in farmed fish. The aim of the study was to assess the
      chemical contaminant load in Atlantic salmon (Salmo salar L.) raised on novel
      sustainable feeds based on a combination of alternative ingredients. Atlantic
      salmon were reared on feeds based on either traditional or alternative feed
      ingredients for an entire seawater production cycle up to approximately 4kg,
      which is a typical market-size for this species. The levels of several notorious
      contaminants were analysed in feed ingredients, feed, and skin-off fillets. These
      included persistent organic pollutants (POPs) such as polychlorinated biphenyls
      (PCBs), dioxins and furans (PCDD/Fs), organochlorine pesticides (OCPs), and
      polybrominated diphenyl ethers (PBDEs), as well as elements such as arsenic,
      mercury, cadmium, lead, copper, zinc and fluorine. In addition, poly-aromatic
      hydrocarbons (PAHs) were analysed. The use of alternative feed ingredients
      reduced the fillet load of POPs by 51-82% and the level of arsenic and mercury by
      80-96%. In contrast, the PAH levels in fish reared on the novel feeds were
      significantly (p<0.05) higher than the PAH concentrations in traditionally-raised
      fish. The present study shows that developments in feed formulation will reduce
      the load of most persistent organic pollutants in farmed salmon, but may increase
      concentrations of other contaminants such as PAHs, which are normally not
      associated with Atlantic salmon. The paper also compares the levels of
      contaminants in farmed Atlantic salmon expected in the future with those levels
      reported in the literature and currently on the market.

PMID- 20045552
TI  - Estimating peer effects in sexual behavior among adolescents.
AB  - In this paper we seek to empirically quantify the role of peer social networks in
      influencing sexual behavior among adolescents. Using data of a nationally
      representative sample of adolescents we utilize a multivariate structural model
      with school-level fixed effects to account for the problems of contextual
      effects, correlated effects and peer selections to purge the potential biases
      from the estimates of peer influence. Our peer group measures are drawn not only
      from the nomination of close friends, but also from classmates. Controlling for
      parent level characteristics, and other demographic parameters, we find that a
      10% increase in the proportion of close friends who initiates sex increases the
      probability that an individual chooses to initiate sex by 5% and a 10% increase
      in number of sexual partners among close friends increases an individual's sexual
      partner by 5%. The influence of classmates however, diminishes in magnitude after
      accounting for unobserved environmental confounders.

PMID- 20045553
TI  - Generation and manipulation of magnetic multicellular spheroids.
AB  - Multicellular spheroids have important applications in tumour studies, drug
      screening and tissue engineering. To enable simple manipulation of spheroids,
      magnetically labelled HeLa cells were cultured in hanging drops to generate
      magnetic spheroids. HeLa cells were labelled by biotinylating their cell membrane
      proteins and then binding streptavidin paramagnetic particles onto the
      biotinylated cell surface. Spheroids of different sizes were obtained by varying
      the seeding cell concentrations within the hanging drops and the spheroids had
      good cell viability. Characterisation of the F-actin distribution within the
      spheroids indicated a three dimensional reorganisation of the cellular
      cytoskeleton compared to monolayer cultures. The magnetic moment of the spheroids
      was measured and showed a superparamagnetic response in an applied field.
      Transmission electron microscopy analysis indicated that the paramagnetic
      particles were still present in the spheroids even after 21 days of culture.
      These spheroids could be easily and quickly separated magnetically without the
      need for centrifugation. The magnetic spheroids were also successfully
      manipulated and patterned using magnetic fields within a few seconds. The
      patterned spheroids then fused together to form a larger tissue construct.

PMID- 20045554
TI  - Poly(3-hydroxybutyrate) multifunctional composite scaffolds for tissue
      engineering applications.
AB  - Poly(3-hydroxybutyrate) (P(3HB)) foams exhibiting highly interconnected porosity
      (85% porosity) were prepared using a unique combination of solvent casting and
      particulate leaching techniques by employing commercially available sugar cubes
      as porogen. Bioactive glass (BG) particles of 45S5 Bioglass grade were introduced
      in the scaffold microstructure, both in micrometer ((m-BG), <5 microm) and
      nanometer ((n-BG), 30 nm) sizes. The in vitro bioactivity of the P(3HB)/BG foams
      was confirmed within 10 days of immersion in simulated body fluid and the foams
      showed high level of protein adsorption. The foams interconnected porous
      microstructure proved to be suitable for MG-63 osteoblast cell attachment and
      proliferation. The foams implanted in rats as subcutaneous implants resulted in a
      non-toxic and foreign body response after one week of implantation. In addition
      to showing bioactivity and biocompatibility, the P(3HB)/BG composite foams also
      exhibited bactericidal properties, which was tested on the growth of
      Staphylococcus aureus. An attempt was made at developing multifunctional
      scaffolds by incorporating, in addition to BG, selected concentrations of Vitamin
      E or/and carbon nanotubes. P(3HB) scaffolds with multifunctionalities (viz.
      bactericidal, bioactive, electrically conductive, antioxidative behaviour) were
      thus produced, which paves the way for next generation of advanced scaffolds for
      bone tissue engineering.

PMID- 20045555
TI  - Resorption of monetite granules in alveolar bone defects in human patients.
AB  - Bone grafting is often required to restore mandibular or maxillary bone volume
      prior to prosthetic tooth root implantation. Preclinical animal models are often
      used to study the in vivo properties of new bone graft products designed for
      human use. Although animal studies may offer valuable data regarding
      bioperformance, materials do not necessarily perform the same in human patients.
      In this study we implanted bovine hydroxyapatite (BH), a widely used porous
      apatite granule, and dicalcium phosphate anhydrous (monetite) granules,
      bilaterally in human patients post extraction alveolar sockets. After six months,
      histomorphometrical analysis of the biopsies revealed that the amount of bone
      regenerated with monetite (59.5 +/- 13%) was significantly higher than that
      obtained with BH (33.1% +/- 4.9), while the amount of unresorbed graft was higher
      in the sockets treated with BH (37.8 +/- 6.1) than in those implanted with
      monetite (25.8 +/- 14.3). Resorption of calcium phosphate ceramics is discussed
      by applying the Hixon-Crowell dissolution model.

PMID- 20045557
TI  - Differences in gene expression dependent on sampling site in placental tissue of
      fetuses with intrauterine growth restriction.
AB  - OBJECTIVE: The human placenta as part of the feto-placental unit may influence
      fetal endocrine systems and may therefore represent a very important link between
      intrauterine growth restriction (IUGR) and metabolic disorders in later life. We
      aimed to analyze the effect of sample origin on gene expression of placental
      factors potentially involved in fetal programming in IUGR versus appropriate for
      gestational age growth (AGA) to standardize sample collection procedure for a
      multicenter approach. DESIGN: Placental gene expression of insulin-like growth
      factor-binding protein (IGFBP)-1, prolactin, corticotropin releasing hormone
      (CRH) and leptin was measured and compared between proximal, intermediate and
      peripheral region of the placenta in 22 IUGR (proven by anomalous placental
      Doppler velocimetry) and 19 AGA neonates. RESULTS: Whereas no difference in gene
      expression was seen in the proximal portion, in the intermediate placental region
      mRNA expression of IGFBP-1 (p = 0.01), prolactin (p = 0.04), CRH (p = 0.01) and
      leptin (p = 0.04) was increased in IUGR samples compared to controls. At the
      placental periphery, gene expression of these placental transcripts showed a
      higher expression level in IUGR placentas without statistical significance,
      except for leptin (p = 0.03). CONCLUSION: Placental sampling site seems to be
      relevant for detecting differences in gene expression between IUGR and AGA
      neonates.

PMID- 20045559
TI  - Mycotic pulmonary artery aneurysm due to Aspergillus infection in a patient with
      leukemia: case report and review of the literature.
AB  - We present a case of a patient with hairy cell leukemia and pulmonary
      aspergillosis who developed a cycotic pulmonary artery aneurysm despite prolonged
      antifungal therapy. A review of the literature in regards to incidence, etiology,
      clinical manifestations and treatment options is included.

PMID- 20045560
TI  - Uncertainties in ecological, chemical and physiological parameters of a
      bioaccumulation model: implications for internal concentrations and tissue based
      risk quotients.
AB  - Bioaccumulation models predict internal contaminant concentrations (c(i)) using
      ecological, chemical and physiological parameters. Here we analyse the effect of
      uncertainties on these parameters on bioaccumulation model predictions.
      Simultaneously considering the uncertainties on all these parameters in a
      bioaccumulation model resulted in uncertainty ranges of c(i) that increased with
      the octanol water partition coefficient K(ow) and reached maxima of up to 1.25
      log units for mesozooplankton and up to 1.45 log units fish at logK(ow)=8. A
      global sensitivity analysis (SA) was performed to rank the contribution of
      different parameters to the observed uncertainty. The SA demonstrated that this
      interspecies difference resulted predominantly from uncertain production rates of
      fish. The K(ow), the water concentration and organic carbon-octanol
      proportionality constant were important drivers of uncertainty on c(i) for both
      species. A tissue based risk quotient (RQ(tissue)) combining uncertainty on c(i)
      with realistic tissue based effect thresholds indicated that fish were up to 10
      times more probable to have RQ(tissue)>1 than mesozooplankton, depending on the
      considered threshold value. Conventional exposure based risk quotients were up to
      5 times less probable to exceed one than were corresponding RQ(tissue), and this
      for both species.

PMID- 20045561
TI  - Central corneal thickness and its association with ocular and general parameters
      in Indians: the Central India Eye and Medical Study.
AB  - PURPOSE: To evaluate the distribution of central corneal thickness (CCT) and its
      associations in an adult Indian population. DESIGN: Population-based study.
      PARTICIPANTS: The Central India Eye and Medical Study is a population-based study
      performed in a rural region close to Nagpur in Central India; it included 4711
      subjects (ages 30+ years) of 5885 eligible subjects (response rate, 80.1%).
      METHODS: The participants underwent a detailed ophthalmic and medical
      examination, including 200 standardized questions on socioeconomic background,
      lifestyle, social relations, and psychiatric depression. This study was focused
      on CCT as measured by sonography and its associations. Intraocular pressure was
      measured by applanation tonometry. MAIN OUTCOME MEASURES: Central corneal
      thickness and intraocular pressure. RESULTS: Central corneal thickness
      measurement data were available on 9370 (99.4%) eyes. Mean CCT was 514+/-33
      microm (median, 517 microm; range, 290-696 microm). By multiple regression
      analysis, CCT was associated significantly with younger age (P<0.001), male
      gender (P<0.001), higher body mass index (P = 0.006), lower corneal refractive
      power (P<0.001), deeper anterior chamber (P = 0.02), thicker lens (P = 0.02), and
      shorter axial length (P = 0.006). Central corneal thickness was not associated
      significantly with refractive error (P = 0.54) or cylindrical refractive error (P
      = 0.20). If eyes with a corneal refractive power of 45 or more diopters were
      excluded, the relationship between CCT and axial length was no longer
      statistically significant (P>0.05), whereas all other relationships remained
      significant. Intraocular pressure readings increased significantly (P<0.001) with
      both higher CCT and higher corneal refractive power. CONCLUSIONS: Indians from
      rural Central India have markedly thinner corneas than do Caucasians or Chinese,
      and, as in other populations, CCT is greater in men. CCT was associated with
      younger age, higher body mass index, lower corneal refractive power, deeper
      anterior chamber, thicker lens, and shorter axial length. Intraocular pressure
      readings were associated with CCT, with high readings in those eyes that had
      thick corneas or steep corneas. Central corneal thickness and steepness of the
      anterior corneal surface may thus both have to be taken into account when
      applanation tonometry is performed. FINANCIAL DISCLOSURE(S): The author(s) have
      no proprietary or commercial interest in any materials discussed in this article.

PMID- 20045558
TI  - Differential regulation of inducible and endothelial nitric oxide synthase by
      kinin B1 and B2 receptors.
AB  - Kinins are vasoactive peptides that play important roles in cardiovascular
      homeostasis, pain and inflammation. After release from their precursor
      kininogens, kinins or their C-terminal des-Arg metabolites activate two distinct
      G protein-coupled receptors (GPCR), called B2 (B2R) or B1 (B1R). The B2R is
      expressed constitutively with a wide tissue distribution. In contrast, the B1R is
      not expressed under normal conditions but is upregulated by tissue insult or
      inflammatory mediators. The B2R is considered to mediate many of the acute
      effects of kinins while the B1R is more responsible for chronic responses in
      inflammation. Both receptors can couple to Galphai and Galphaq families of G
      proteins to release mediators such as nitric oxide (NO), arachidonic acid,
      prostaglandins, leukotrienes and endothelium-derived hyperpolarizing factor and
      can induce the release of other inflammatory agents. The focus of this review is
      on the different transduction events that take place upon B2R and B1R activation
      in human endothelial cells that leads to generation of NO via activation of
      different NOS isoforms. Importantly, B2R-mediated eNOS activation leads to a
      transient ( approximately 5min) output of NO in control endothelial cells whereas
      in cytokine-treated endothelial cells, B1R activation leads to very high and
      prolonged ( approximately 90min) NO production that is mediated by a novel signal
      transduction pathway leading to post-translational activation of iNOS.

PMID- 20045562
TI  - Combination of rituximab and intravenous immunoglobulin for recalcitrant ocular
      cicatricial pemphigoid: a preliminary report.
AB  - PURPOSE: To compare the effectiveness and safety of the combination therapy of
      rituximab (RTX) and intravenous immunoglobulin (IVIg) to other immunosuppressive
      regimens in the treatment of ocular cicatricial pemphigoid (OCP). DESIGN:
      Retrospective, comparative, interventional case series. PARTICIPANTS: Twelve
      patients with OCP. METHODS: We reviewed medical records of 12 patients with OCP.
      Ten of the 12 patients were blind in 1 eye after initial systemic
      immunosuppressive therapies (phase 1 treatment). The patients were then divided
      into 2 groups based on treatments received during phase 2. The study group
      consisted of 6 patients who received the combination of RTX and IVIg during phase
      2 of their treatment. For comparison purposes, the control group consisted of 6
      patients who during phase 2 of their treatment received more aggressive
      immunosuppressive therapies, but not RTX and IVIg, because the insurance carriers
      refused to pay for the combination therapy. MAIN OUTCOME MEASURES: Blindness
      (best-corrected visual acuity [BCVA] < or =20/200) and OCP staging (Foster).
      RESULTS: The median total follow-up periods were 57.5 and 55.5 months in the
      control group and the study group, respectively. After phase 1 treatment, all 6
      patients in the control group were blind in 1 eye. Similarly, 4 of the patients
      in the study group were blind in 1 eye, whereas 2 had good BCVA bilaterally but
      experienced persistent conjunctival inflammation despite phase 1 treatment. After
      phase 2 treatment, all 6 patients in the control group had OCP progression and
      became blind in both eyes. In contrast, BCVA was stable and no further
      progression of OCP staging was observed in all 6 patients in the study group. In
      the study group, the median follow-up from completion of the RTX and IVIg
      treatment protocol was 11 months. No adverse events, immediate or delayed, were
      reported in any of the patients who received the combination therapy of RTX and
      IVIg. CONCLUSIONS: In this preliminary study, the combination therapy of RTX and
      IVIg arrested disease progression and prevented total blindness in patients with
      recalcitrant OCP.

PMID- 20045563
TI  - In vivo retinal morphology after grid laser treatment in diabetic macular edema.
AB  - PURPOSE: To analyze immediate in vivo intraretinal morphologic changes secondary
      to standardized grid photocoagulation using spectral domain optical coherence
      tomography (SD OCT). DESIGN: Prospective clinical trial. PARTICIPANTS: Thirteen
      consecutive patients with treatment-naive clinically significant diabetic macular
      edema (DME). METHODS: Before and 1 day after standardized grid photocoagulation
      using the PASCAL system (Pattern Scan Laser, OptiMedica Corporation, Santa Clara,
      CA), Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) examinations
      based on an eye-tracking system, infrared fundus imaging, color fundus
      photography, and biomicroscopy were performed. A standardized visual acuity
      assessment (Early Treatment Diabetic Retinopathy Study protocol) and fluorescein
      angiography were performed at baseline. MAIN OUTCOME MEASURES: Morphologic
      changes secondary to grid laser treatment. RESULTS: One day after laser therapy,
      immediate morphologic alterations of only the outer retinal layers, that is, the
      retinal pigment epithelium (RPE), the photoreceptor layer (PRL), and the outer
      nuclear layer (ONL), were observed. The shape of the laser-induced lesions did
      not show a sagittal alteration pattern throughout all 3 of the layers, however,
      but rather seemed to follow an oblique pathway throughout the ONL, changing
      direction at the level of the external limiting membrane and proceeding
      sagittally through the PRL and RPE. These morphologic changes also induced
      biometric changes, such as a decrease in central retinal thickness combined with
      local thickening at the lesion site, especially in the PRL. CONCLUSIONS: Spectral
      domain optical coherence tomography provides new insight into the immediate
      morphologic changes after laser treatment using the PASCAL laser system.
      Standardized grid photocoagulation induces characteristic homogenous alteration
      in the neurosensoric retinal layers. Biometric changes, indicating an immediate
      effect, were observed within 1 day after treatment.

PMID- 20045564
TI  - The Heidelberg retina tomograph Glaucoma Probability Score: reproducibility and
      measurement of progression.
AB  - PURPOSE: To evaluate the reproducibility of the Heidelberg retina tomograph (HRT)
      Glaucoma Probability Score (GPS) and assess its potential for monitoring
      progression. DESIGN: Evaluation of diagnostic tests in a randomized, controlled
      clinical trial. PARTICIPANTS: For reproducibility, we included 43 ocular
      hypertensive (OHT) and 31 glaucoma subjects. For progression, we included 198 OHT
      and 21 control subjects. METHODS: To study reproducibility, global GPS values
      were generated for HRT images acquired in a test-retest study. Images were
      acquired at 2 visits within 6 weeks of each other, by 2 different observers. To
      study progression, GPS values were generated for HRT images acquired
      prospectively (1993-2001). Linear regression of GPS against time was performed,
      with progression defined as a significant negative slope (P<0.05). Criterion
      specificity was estimated from the number of improving subjects (significant
      positive slope) and the number of progressing controls. Visual field (VF)
      progression in the same subjects was assessed using 3-omitting pointwise linear
      regression of sensitivity over time. MAIN OUTCOME MEASURES: Reproducibility of
      GPS was assessed using Bland-Altman analysis (mean difference, 95% limits of
      agreement). Progression was assessed by the number of OHT subjects identified as
      progressing, and by agreement with VF progression. RESULTS: Reproducibility of
      GPS was better at its extremes (-0.01+/-0.20 for GPS 0-0.30, and 0.02+/-0.09 for
      GPS 0.78-1.00) than in its mid range (0.07+/-0.54 for GPS 0.30-0.78). Estimated
      criterion specificity ranged from 95.2% (95% confidence interval, 76.1%-99.9%) to
      96.8% (93.2%-98.5%). Twenty-five OHT subjects (12.6%) progressed by GPS, with 11
      of the 25 (5.6%) also progressing by VF; 26 subjects (13.1%) progressed by VF
      alone. CONCLUSIONS: Changes in HRT GPS values between 0.30 and 0.78 should be
      interpreted with caution because the index has poorer reproducibility in this
      range. The global GPS progression algorithm performs at least as well as
      previously described rim area-based HRT progression strategies. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 20045565
TI  - Influence of serum lipids on clinically significant versus nonclinically
      significant macular edema: SN-DREAMS Report number 13.
AB  - PURPOSE: To estimate the prevalence of diabetic macular edema, both clinically
      significant macular edema (CSME) and nonclinically significant macular edema (non
      CSME), and report the associations of dyslipidemia on them. DESIGN: A population
      based cross-sectional study in India. PARTICIPANTS: After all exclusions, 1414
      subjects with diabetes underwent an examination. METHODS: The CSME was defined
      according to the Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines;
      stereo digital fundus pairs were studied. The dyslipidemia cases were classified
      according to the National Cholesterol Education Program-Adult Treatment Panel III
      (NCEP-ATP III). MAIN OUTCOME MEASURES: Prevalence of CSME and non-CSME and
      association of serum lipids with them. RESULTS: The prevalence was 31.76% (95%
      confidence interval [CI], 26.04-37.47) for overall diabetic macular edema, 25.49%
      (95% Ci, 20.14-30.84) for non-CSME, and 6.27% (95% Ci, 3.29-9.24) for CSME.
      Univariate analysis identified macroalbuminuria and microalbuminuria, poor
      glycemic control, high total serum cholesterol, high serum low-density
      lipoprotein (LDL) cholesterol, and high serum non-high-density lipoprotein (HDL)
      cholesterol related to non-CSME and CSME (trend chi-square test, P<0.05).
      Logistic regression analysis (after adjusting variables such as age, gender, body
      mass index, duration, smoking, hypertension, glycosylated hemoglobin,
      macroalbuminuria and microalbuminuria, and insulin use) revealed high serum LDL
      cholesterol (odds ratio [OR], 2.72], high serum non-HDL cholesterol (OR, 1.99),
      and high cholesterol ratio (OR, 3.08) related to non-CSME, and poor glycemic
      control (OR, 8.06), microalbuminuria (OR, 14.23), and high serum total
      cholesterol (OR, 9.09) related to CSME. CONCLUSIONS: One third of the subjects
      had diabetic macular edema, and 6% of them showed evidence of CSME necessitating
      laser photocoagulation. FINANCIAL DISCLOSURE(S): The author(s) have no
      proprietary or commercial interest in any materials discussed in this article.

PMID- 20045566
TI  - Hormone replacement therapy in relation to risk of cataract extraction: a
      prospective study of women.
AB  - OBJECTIVE: To investigate the association between hormone replacement therapy
      (HRT) and the incidence of cataract extraction among postmenopausal women.
      DESIGN: Population-based, prospective cohort study. PARTICIPANTS: A total of 30
      861 postmenopausal women participating in the Swedish Mammography Cohort, age 49
      to 83 years, who completed a self-administered questionnaire in 1997 about
      hormone status, HRT, and lifestyle factors. METHODS: The women were followed from
      September 1997 through October 2005. The cohort was matched with registers of
      cataract extraction in the study area. MAIN OUTCOME MEASURES: Incident operative
      extraction of age-related cataract. RESULTS: We identified 4324 incident cases of
      cataract extractions during 98 months of follow-up. In multivariate adjusted
      analysis, ever use of HRT was associated with a 14% increased risk of cataract
      extraction (rate ratio [RR], 1.14; 95% confidence interval [CI], 1.07-1.21)
      compared with those who never used HRT. Current use of HRT was associated with an
      18% increased risk of cataract extraction (RR, 1.18; 95% CI, 1.10-1.26). A
      significant linear trend was observed where increasing duration of HRT usage
      resulted in an increased risk of cataract extraction (P for trend = 0.006).
      Multivariate RR for current HRT usage for >10 years was 1.20 (95% CI, 1.06-1.36;
      P for trend = 0.001). Among women drinking on average >1 drink of alcohol per
      day, current HRT users had a 42% increased risk (RR, 1.42; 95% CI, 1.11-1.80) for
      cataract extraction, compared with women who neither used HRT nor alcohol. The
      risk of cataract extraction among current users of HRT was similar among current
      smokers and those who never smoked. CONCLUSIONS: Our prospective, population
      based study indicates that postmenopausal women using HRT for a long period of
      time may be at an increased risk for cataract extraction, especially those
      drinking >1 alcoholic drink daily.

PMID- 20045567
TI  - Spectral-domain optical coherence tomography for monitoring epiretinal membrane
      surgery.
AB  - PURPOSE: To assess prognostic factors in epiretinal membrane (ERM) surgery using
      spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Prospective,
      interventional case series. PARTICIPANTS: Forty-one patients. METHODS: Patients
      with a diagnosis of ERM were examined with spectral-domain and time-domain (TD)
      OCT before and after surgery. MAIN OUTCOME MEASURES: Main outcome measures were
      functional results and predefined OCT patterns. Cofactors analyzed were the type
      of ERM, the duration and grading of subjective metamorphopsia, simultaneous
      cataract surgery, the type of dyes used, the duration of surgery, gender, and
      age. A multivariate regression analysis was performed. RESULTS: Thirty-nine
      patients (95%) showed an improved or stable best-corrected distance visual acuity
      (DVA) at 3 months, whereas 36 patients (88%) showed an improved or stable best
      corrected near visual acuity (NVA) at 3 months. Significant correlations (P>0.4)
      were found between the course of central retinal thickness (CRT) assessed using
      SD OCT and TD OCT (P<0.02). No clinically relevant correlations (P<0.3) were seen
      between CRT and VA (P>0.1). Baseline DVA and NVA were found to be significant
      prognostic values for the postoperative decrease in CRT in both OCT systems
      (P<0.04) as well as for the visual outcomes (P<0.007) at 3 months. In addition,
      the integrity of the junction between the photoreceptor inner segment and outer
      segment (IS/OS) significantly influenced the visual outcomes at 3 months
      (P<0.038). The baseline profile of the internal limiting membrane (ILM)
      significantly influenced the NVA at 3 months (P<0.009), whereas the postoperative
      foveal contour significantly influenced the DVA at 3 months (P<0.025). The type
      of ERM, subjective metamorphopsia, simultaneous cataract surgery, the type of
      dyes used, the duration of surgery, gender, or age had no significant influence
      on patient outcome (P>0.05). Compared with TD OCT, SD OCT allowed for a more
      precise differentiation between the ERM and the retinal surface and for a better
      evaluation of the IS/OS line. CONCLUSIONS: Besides the baseline VA, the integrity
      of the IS/OS line, better visualized by SD OCT, can be used to predict the
      functional outcomes after surgery. Additionally, analyzing the ILM profile and
      the foveal contour may help to understand limited visual outcomes after surgery.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 20045568
TI  - Simvastatin and disease stabilization in normal tension glaucoma: a cohort study.
AB  - PURPOSE: To investigate whether simvastatin use is associated with visual field
      (VF) stabilization in patients with normal tension glaucoma (NTG). DESIGN:
      Prospective cohort study (ClinicalTrials.gov Identifier: NCT00321386).
      PARTICIPANTS: A total of 256 eyes from 256 Chinese subjects with NTG. METHODS:
      Patients were followed up at 4-month intervals for 36 months for VF progression
      per Anderson's criteria. Clinical parameters were checked for association with
      progression in multivariate analysis. MAIN OUTCOME MEASURES: The primary outcome
      was the association between simvastatin use and VF progression. RESULTS: Thirty
      one patients (12.1%) were taking simvastatin (statin+), and 225 patients (87.9%)
      were not taking simvastatin (statin-). Baseline age, gender, untreated
      intraocular pressure, VF indices, vertical cup-to-disc ratio, and central corneal
      thickness (CCT) were comparable between the 2 groups. There were significantly
      more patients with a history of hypercholesterolemia, systemic hypertension, and
      ischemic heart disease in the statin+ group. A total of 121 patients (47.3%)
      showed evidence of VF progression (mean rate of mean deviation loss was -0.30
      decibel per year) during the 36 months of follow-up. Simvastatin use was among 8
      of 121 patients (6.6%) who progressed compared with 23 of 135 patients (17.0%)
      who did not progress (P = 0.011). Logistic regression revealed that history of
      disc hemorrhage (relative risk [RR] 3.26; 95% confidence interval [CI], 1.21
      8.76; P = 0.019), history of cerebrovascular accidents (RR 2.28; 95% CI, 1.03
      5.06; P = 0.043), and baseline age (per 10 years older; RR 1.38; 95% CI, 1.08
      1.76; P = 0.009) were significant risk factors for VF progression, whereas
      simvastatin use conferred a protective effect (RR 0.36; 95% CI, 0.14-0.91; P =
      0.030). CONCLUSIONS: Simvastatin use may be associated with VF stabilization in
      patients with NTG. A larger scale randomized controlled trial and cost
      effectiveness analyses seem warranted.

PMID- 20045569
TI  - Refractive error in central India: the Central India Eye and Medical Study.
AB  - OBJECTIVE: To evaluate the refractive error and its associations in the adult
      population of rural Central India. DESIGN: Population-based study. PARTICIPANTS:
      The Central India Eye and Medical Study is a population-based study performed in
      a markedly rural region in Central India. It included 4711 subjects (aged 30
      years or older) of 5885 eligible subjects (response rate, 80.1%). METHODS: The
      participants underwent a detailed ophthalmic and medical examination, including
      standardized questions on the socioeconomic background, lifestyle, and social
      relations. This study was focused on the refractive error, the prevalence of
      hyperopia and myopia, and its factors. MAIN OUTCOME MEASURES: Refractive error.
      RESULTS: After exclusion of pseudophakic or aphakic eyes, 9076 (96.3%) eyes of
      4619 (98.0%) subjects (2472 females) were included into the study. The mean
      refractive error was -0.20+/-1.51 diopters (D). Myopia of more than -0.50 D, -1.0
      D, more than -6.0 D, and more than -8 D occurred in 17.0+/-0.6%, 13.0+/-0.5%,
      0.9+/-1.4%, and 0.4+/-0.1% of the subjects, respectively. Hyperopia of more than
      0.50 D was detected in 18.0+/-0.6% of the subjects. Refractive error was
      associated significantly (i.e., became more hyperopic) with lower age (P<0.001),
      lower best-corrected visual acuity (P<0.001), lower corneal refractive power
      (P<0.001), and shorter axial length (P<0.001). In multivariate analysis,
      refractive error was not significantly associated with the level of education (P
      = 0.56). High myopia (>-8 D) was associated significantly with male gender (P =
      0.03) and lower best-corrected visual acuity (P<0.001). Mean anisometropia was
      0.41+/-1.02 D. It was associated significantly with age (P<0.001), myopic
      refractive error (P<0.001), and lower best-corrected visual acuity (P<0.001). The
      mean astigmatic error was 0.29+/-0.60 D and was associated significantly with
      higher age (P<0.001), level of education (P = 0.01), lower best-corrected visual
      acuity (P<0.001), and higher corneal refractive power (P<0.001). CONCLUSIONS: The
      rural population of Central India has not experienced a myopic shift as described
      for many urban populations at the Pacific Rim. Correspondingly, the relatively
      low level of education was not associated with myopia. Urbanization may be a
      major factor for myopization. FINANCIAL DISCLOSURE(S): Proprietary or commercial
      disclosure may be found after the references.

PMID- 20045570
TI  - Ultra wide-field angiographic characteristics of branch retinal and hemicentral
      retinal vein occlusion.
AB  - PURPOSE: To study the peripheral angiographic features of branch retinal vein
      occlusions (BRVO) and hemicentral retinal vein occlusions (HRVO) and explore
      associations with macular edema and neovascularization. DESIGN: Retrospective
      observational case series. PARTICIPANTS: Seventy-eight outpatients. METHODS: An
      imaging database of angiograms performed at a single academic institution was
      searched for patients with a diagnosis of BRVO or HRVO. Images were graded for
      the presence of untreated nonperfusion (areas without evidence of laser
      photocoagulation), late peripheral vascular leakage (LPVL), neovascularization,
      macular edema, and prior laser treatment. Optical coherence tomography images
      were reviewed for all patients to confirm the presence of macular thickening and
      to exclude eyes with vitreomacular traction. MAIN OUTCOME MEASURES: Angiographic
      evidence of nonperfusion, neovascularization, macular edema, LPVL, and prior
      laser treatment. RESULTS: Angiograms from 80 eyes of 78 patients were analyzed
      with a diagnosis of BRVO (86%) or HRVO (14%). Angiographic macular edema (80%),
      untreated nonperfusion (82%), neovascularization (21%), and LPVL (58%) were
      observed. Untreated nonperfusion at any location was significantly associated
      with macular edema (P = 0.043). Untreated nonperfusion anterior to the globe
      equator was significantly associated with macular edema (P = 0.007). Untreated
      nonperfusion was significantly associated with the presence of neovascularization
      (P = 0.033). Late peripheral vascular leakage was not associated with other
      angiographic or clinical findings studied. CONCLUSIONS: Ultra wide-field
      angiography provides visualization of peripheral retinal pathology in BRVO and
      HRVO patients, which may be useful in their evaluation and treatment. Our
      findings support the hypothesis that areas of untreated retinal nonperfusion may
      be the source of production of biochemical mediators that promote
      neovascularization and macular edema. FINANCIAL DISCLOSURE(S): Proprietary or
      commercial disclosure may be found after the references.

PMID- 20045571
TI  - Clinical assessment of stereoscopic optic disc photographs for glaucoma: the
      European Optic Disc Assessment Trial.
AB  - PURPOSE: To determine the diagnostic accuracy of judging optic disc photographs
      for glaucoma by ophthalmologists. DESIGN: Evaluation of diagnostic test and
      technology. PARTICIPANTS: A total of 243 of 875 invited ophthalmologists in 11
      European countries. METHODS: We determined how well each participant classified
      40 healthy eyes and 48 glaucomatous eyes with varying severity of the disease on
      stereoscopic slides. Duplicate slides were provided for determining intraobserver
      agreement. All eyes were also imaged with the GDx with variable corneal
      compensation (GDx-VCC) (Carl Zeiss Meditec AG, Jena, Germany) and the Heidelberg
      Retina Tomograph (HRT) I (Heidelberg Engineering GmbH, Heidelberg, Germany).
      Diagnostic accuracies of clinicians were compared with those of the best machine
      classifiers. MAIN OUTCOME MEASURES: Accuracy of classification, expressed as
      sensitivity, specificity, and overall accuracy. Intraobserver agreement (kappa).
      RESULTS: The overall diagnostic accuracy of ophthalmologists was 80.5% (standard
      deviation [SD], 6.8; range, 61.4%-94.3%). The machine classifiers outperformed
      most observers in diagnostic accuracy; the GDx-VCC nerve fiber indicator and the
      HRT's best classifier correctly classified 93.2% and 89.8% of eyes, respectively.
      The intraobserver agreement (kappa) varied between -0.13 and 1.0 and was on
      average good (0.7). CONCLUSIONS: In general, ophthalmologists classify optic disc
      photographs moderately well for detecting glaucoma. There is, however, large
      variability in diagnostic accuracy among and agreement within clinicians. Common
      imaging devices outperform most clinicians in classifying optic discs. FINANCIAL
      DISCLOSURE(S): Proprietary or commercial disclosure may be found after the
      references.

PMID- 20045572
TI  - Paraneoplastic conjunctival cicatrization: two different pathogenic types.
AB  - PURPOSE: To describe the clinical and immunopathologic features of patients with
      2 different types of paraneoplastic conjunctival cicatrization. DESIGN:
      Retrospective observational case analyses with a review of the literature.
      PARTICIPANTS: One patient with paraneoplastic ocular cicatricial pemphigoid
      (POCP) and 1 patient with paraneoplastic pemphigus (PNP) with ocular involvement.
      METHODS: Critical review of clinical history, diagnostic studies, and
      immunopathologic results of biopsies in the 2 cases, together with a review of
      the literature. MAIN OUTCOME MEASURES: Ability to recognize paraneoplastic
      conjunctival cicatrization and to diagnose the conditions accurately. RESULTS:
      The first patient, 46 years of age, presented with conjunctival scarring and
      symblephara, cough, oral lesions, and chest rash. Concurrently, a diagnosis of
      pulmonary squamous cell carcinoma was made. Conjunctival biopsy revealed a
      subepithelial bulla, an inflammatory infiltrate of T and B lymphocytes, and
      basement membrane zone deposition of immunoglobulin (Ig)-G and C3 consistent with
      POCP. The second patient, 54 years of age, had a recently diagnosed B-cell
      chronic lymphocytic leukemia, followed 1 month later with ocular irritation and
      bilateral extensive symblephara. Extensive oral lesions and skin involvement of
      the lower half of the body were seen. Skin biopsy disclosed subepidermal bullae
      and mostly T cells with virtually no B cells in the dermal infiltrate (the
      patient was being treated with rituximab). Linear subepithelial deposition of IgG
      and C3 and deposition within the epidermis were consistent with PNP. Further
      indirect immunofluorescence and immunoprecipitation studies with the patient's
      serum-derived antibodies established PNP as the definitive diagnosis.
      CONCLUSIONS: Underlying malignancy is an important consideration in younger
      patients with puzzling bilateral cicatrizing conjunctivitis, and a paraneoplastic
      condition can be established from either a conjunctival or a skin biopsy.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 20045573
TI  - Novel therapy for transthyretin-related ocular amyloidosis: a pilot study of
      retinal laser photocoagulation.
AB  - OBJECTIVE: The occurrence of ocular complications associated with transthyretin
      related familial amyloidotic polyneuropathy increases with time, even after liver
      transplantation, which leads to a halt in the progression of systemic neurologic
      complications. This study investigated a new strategy to prevent ocular
      involvements. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients
      with familial amyloidotic polyneuropathy who had progressive ocular
      manifestations. METHODS: We used panretinal laser photocoagulation, which damages
      the retinal pigment epithelium, the main location for synthesis of amyloidogenic
      transthyretin in ocular tissues, to treat 1 eye of each patient. After laser
      photocoagulation, we performed general ophthalmic examinations every 3 months for
      3 years. MAIN OUTCOME MEASURES: Fundus photography, visual acuity, and
      intraocular pressure. RESULTS: Panretinal laser photocoagulation clearly
      prevented progression of amyloid deposition in the vitreous and on the retinal
      surface in both cases during 3 years of follow-up. No serious complications
      occurred. CONCLUSIONS: Panretinal laser photocoagulation is a safe and well-known
      procedure that offers a new treatment option to mitigate ocular manifestations in
      patients with transthyretin-related familial amyloidotic polyneuropathy.

PMID- 20045574
TI  - Hydrocortisone induced hypertrophic cardiomyopathy.
AB  - A preterm infant developed recurrent, hypertrophic obstructive cardiomyopathy
      (HOCM) on administration of steroids which resolved after discontinuation of the
      drug. Following a course of hydrocortisone for treatment of broncho-pulmonary
      dysplasia, echocardiography showed left ventricular hypertrophy with outflow
      tract obstruction, resolving on stopping the drug, only to recur after a second
      course.

PMID- 20045575
TI  - Keeping track of congenital heart disease--is it time for a national registry?
AB  - Considerable improvements have been made in care and provision for patients with
      congenital heart disease in the United Kingdom. However, delayed presentation of
      adult patients with sequelae of known childhood cardiac defects reflects the
      current situation that there is no national registry of patients with congenital
      heart disease, and this "lost cohort" of patients is difficult to trace.
      Maintaining regular follow-up for selected patients with congenital heart disease
      can be challenging for a variety of reasons, but remains particularly important
      as emerging therapies and treatment strategies continue to alter management.
      Despite recent calls from a variety of organisations to establish a national
      registry of patients with congenital heart disease, progress has been slow. Faced
      with competition for resources, the costs of such a venture may be cited as a
      likely hurdle, but the potential advantages for patients and healthcare providers
      alike justify calls to integrate a registry as part of the ongoing reorganisation
      of congenital heart services in the United Kingdom.

PMID- 20045576
TI  - A prospective, randomized trial of intravenous prochlorperazine versus
      subcutaneous sumatriptan in acute migraine therapy in the emergency department.
AB  - STUDY OBJECTIVE: Intravenous (IV) prochlorperazine with diphenhydramine is
      superior to subcutaneous sumatriptan in the treatment of migraine patients
      presenting to the emergency department (ED). METHODS: In this randomized, double
      blind, placebo-controlled trial, after providing written informed consent,
      patients presenting to the ED with a chief complaint of migraine received a 500
      mL bolus of IV saline solution and either 10 mg prochlorperazine with 12.5 mg
      diphenhydramine IV plus saline solution placebo subcutaneously or saline solution
      placebo IV plus 6 mg sumatriptan subcutaneously. Pain intensity was assessed with
      100-mm visual analog scales (visual analog scale at baseline and every 20 minutes
      for 80 minutes). The primary outcome was change in pain intensity from baseline
      to 80 minutes or time of ED discharge if subjects remained in the ED for fewer
      than 80 minutes after treatment. Sedation and nausea were assessed every 20
      minutes with visual analog scale scales, and subjects were contacted within 72
      hours to assess headache recurrence. RESULTS: Sixty-eight subjects entered the
      trial, with complete data for 66 subjects. Baseline pain scores were similar for
      the prochlorperazine/diphenhydramine and sumatriptan groups (76 versus 71 mm).
      Mean reductions in pain intensity at 80 minutes or time of ED discharge were 73
      mm for the prochlorperazine/diphenhydramine group and 50 mm for those receiving
      sumatriptan (mean difference 23 mm; 95% confidence interval 11 to 36 mm).
      Sedation, nausea, and headache recurrence rates were similar. CONCLUSION: IV
      prochlorperazine with diphenhydramine is superior to subcutaneous sumatriptan in
      the treatment of migraine.

PMID- 20045577
TI  - Defining the emergency care sensitive condition: a health policy research agenda
      in emergency medicine.

PMID- 20045578
TI  - A statewide prescription monitoring program affects emergency department
      prescribing behaviors.
AB  - STUDY OBJECTIVE: Ohio recently instituted an online prescription monitoring
      program, the Ohio Automated Rx Reporting System (OARRS), to monitor controlled
      substance prescriptions within Ohio. This study is undertaken to identify the
      influence of OARRS data on clinical management of emergency department (ED)
      patients with painful conditions. METHODS: This prospective quasiexperimental
      study was conducted at the University of Toledo Medical Center Emergency
      Department during June to July 2008. Eligible participants included ED patients
      with painful conditions. Patients with acute injuries were excluded. After
      clinical evaluation, and again after presentation of OARRS data, providers
      answered a set of questions about anticipated pain prescription for the patient.
      Outcome measures included changes in opioid prescription and other potential
      factors that influenced opioid prescription. RESULTS: Among 179 participants,
      OARRS data revealed high numbers of narcotics prescriptions filled in the most
      recent 12 months (median 7; range 0 to 128). Numerous providers prescribed
      narcotics for patients (median 3 per patient; range 0 to 40). Patients had filled
      narcotics prescriptions at different pharmacies (mean [SD] 3.5 [4.4]). Eighteen
      providers are represented in the study. Four providers treated 63% (N=114) of the
      patients in the study. After review of the OARRS data, providers changed the
      clinical management in 41% (N=74) of cases. In cases of altered management, the
      majority (61%; N=45) resulted in fewer or no opioid medications prescribed than
      originally planned, whereas 39% (N=29) resulted in more opioid medication than
      previously planned. CONCLUSION: The use of data from a statewide narcotic
      registry frequently altered prescribing behavior for management of ED patients
      with complaints of nontraumatic pain.

PMID- 20045581
TI  - [Metformin-associated hepatotoxicity].
AB  - Metformin is an oral biguanide widely used in the management of patients with
      type 2 diabetes. It produces non-specific gastrointestinal symptoms in 10-30% of
      the patients. Lactic acidosis is the most serious side effect, so it must not be
      administered to patients with renal, liver, or heart insufficiency. Only a few
      cases of hepatotoxicity due to this drug have been documented. We report the case
      of a patient with type 2 diabetes mellitus and recent use of metformin who
      developed serious liver injury, followed by a favorable evolution.

PMID- 20045579
TI  - Intramuscular cobinamide sulfite in a rabbit model of sublethal cyanide toxicity.
AB  - STUDY OBJECTIVE: Exposure to cyanide in fires and industrial exposures and
      intentional cyanide poisoning by terrorists leading to mass casualties is an
      ongoing threat. Current treatments for cyanide poisoning must be administered
      intravenously, and no rapid treatment methods are available for mass casualty
      cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an
      extraordinarily high affinity for cyanide that is more water-soluble than
      cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse
      cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure
      animal model and determine the ability of an intramuscular cobinamide sulfite
      injection to rapidly reverse the physiologic effects of cyanide toxicity.
      METHODS: New Zealand white rabbits were given 10 mg sodium cyanide intravenously
      over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave
      near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin
      concentrations were performed concurrently with blood cyanide level measurements
      and cobinamide levels. Immediately after completion of the cyanide infusion, the
      rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive
      vehicle (controls, n=5). RESULTS: Intramuscular administration led to rapid
      mobilization of cobinamide and was extremely effective at reversing the
      physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin
      extraction. Recovery time to 63% of their baseline values in the central nervous
      system occurred within a mean of 1,032 minutes in the control group and 9 minutes
      in the cobinamide group, with a difference of 1,023 minutes (95% confidence
      interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24
      minutes, with a difference of 52 minutes (95% confidence interval 7 to 98
      minutes). RBC cyanide levels returned toward normal significantly faster in
      cobinamide sulfite-treated animals than in control animals. CONCLUSION:
      Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic
      effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can
      be developed for mass casualty cyanide exposures.

PMID- 20045580
TI  - Clinical features from the history and physical examination that predict the
      presence or absence of pulmonary embolism in symptomatic emergency department
      patients: results of a prospective, multicenter study.
AB  - STUDY OBJECTIVE: Prediction rules for pulmonary embolism use variables explicitly
      shown to estimate the probability of pulmonary embolism. However, clinicians
      often use variables that have not been similarly validated, yet are implicitly
      believed to modify probability of pulmonary embolism. The objective of this study
      is to measure the predictive value of 13 implicit variables. METHODS: Patients
      were enrolled in a prospective cohort study from 12 centers in the United States;
      all had an objective test for pulmonary embolism (D-dimer, computed tomographic
      angiography, or ventilation-perfusion scan). Clinical features including 12
      predefined previously validated (explicit) variables and 13 variables not part of
      existing prediction rules (implicit) were prospectively recorded at presentation.
      The primary outcome was venous thromboembolism (pulmonary embolism or deep venous
      thrombosis), diagnosed by imaging up to 45 days after enrollment. Variables with
      adjusted odds ratios from logistic regression with 95% confidence intervals not
      crossing unity were considered significant. RESULTS: Seven thousand nine hundred
      forty patients (7.2% venous thromboembolism positive) were enrolled. Mean age was
      49 years (standard deviation 17 years) and 67% were female patients. Eight of 13
      implicit variables were significantly associated with venous thromboembolism;
      those with an adjusted odds ratio (OR) greater than 1.5 included non-cancer
      related thrombophilia (OR 1.99), pleuritic chest pain (OR 1.53), and family
      history of venous thromboembolism (OR 1.51). Implicit variables that predicted no
      venous thromboembolism outcome included substernal chest pain, female sex, and
      smoking. Nine of 12 explicit variables predicted a positive outcome of venous
      thromboembolism, including patient history of pulmonary embolism or deep venous
      thrombosis in the past, unilateral leg swelling, recent surgery, estrogen,
      hypoxemia, and active malignancy. CONCLUSION: In symptomatic outpatients being
      considered for possible pulmonary embolism, non-cancer-related thrombophilia,
      pleuritic chest pain, and family history of venous thromboembolism increase
      probability of pulmonary embolism or deep venous thrombosis. Other variables that
      are part of existing pretest probability systems were validated as important
      predictors in this diverse sample of US emergency department patients.

PMID- 20045582
TI  - Pharmacophoric model building for antitubercular activity of the individual
      Schiff bases of small combinatorial library.
AB  - Synthesis and evaluation of anti-TB activity of individual compounds of Schiff
      bases combinatorial library were done against Mycobacterium tuberculosis H(37)Rv
      at a single concentration of 6.25mug/mL according to the protocol of TAACF.
      Compounds 2C and 3D produced 99% inhibitory activity on the investigated
      organism, while the other tested compounds showed lower activity ranging from 35
      to 84%. It was found that there are no relation between the anti-TB activity of
      the tested compounds and their lipophilicity expressed by ClogP of these
      compounds. A 3D pharmacophoric model has been generated by Molecular Operating
      Environment (MOE) using a training set of 10 reported anti-TB compounds and
      testing the synthesized compounds (1A, 1B, 1D, 1E, 2C, 3A, 3C, 3D, 3E and 4A-4E).
      The generated pharmacophoric features include, F1: hydrogen bond donors (Don),
      F2: aromatic rings (Aro), F3: hydrogen bond acceptors (Acc)/metal ligator (ML),
      F4: Aro/hydrophobic (Hyd). In all hit set, it was found that the amidic nitrogen
      CONH-NC fitted the region of the Don, F1, while the amidic carbonyl group fitted
      the region of the Acc/ML, F3. The distances bridging F1 to F2, F3 and F4 were
      essential for anti-TB activity in the developed pharmacophore model, as it was
      confirmed from model validation procedure.

PMID- 20045583
TI  - Nursing students' perception of a Web-based intervention to support learning.
AB  - Tailoring information to the needs of the learner is an important strategy in
      contemporary education settings. Web-based learning support, informed by
      multimedia theory, comprising interactive quizzes, glossaries with audio, short
      narrated Power Point(R) presentations, animations and digitised video clips were
      introduced in a first year Bachelor of Nursing biological sciences subject at a
      university in metropolitan Sydney. All students enrolled in this unit were
      invited to obtain access to the site and the number of hits to the site was
      recorded using the student tracking facility available on WebCT, an online course
      delivery tool adopted widely by many educational institutions and used in this
      study. Eighty-five percent of students enrolled in the subject accessed the
      learning support site. Students' perception of the value of a learning support
      site was assessed using a web-based survey. The survey was completed by 123
      participants, representing a response rate of 22%. Three themes emerged from the
      qualitative data concerning nursing students' perception of the web-based
      activities: 'enhances my learning', 'study at my own pace', and 'about the
      activities: what I really liked/disliked'. Web-based interventions, supplementing
      a traditionally presented nursing science course were perceived by students to be
      beneficial in both learning and language development. Although students value
      interactive, multimedia learning they were not ready to completely abandon
      traditional modes of learning including face-to-face lectures. The findings of
      this study contribute to an understanding of how web-based resources can be best
      used to support students' learning in bioscience.

PMID- 20045584
TI  - The home as an appropriate setting for women undertaking cervical ripening before
      the induction of labour.
AB  - OBJECTIVES: to explore women's experiences of cervical ripening using isosorbide
      mononitrate (IMN) in the home as part of the main randomised controlled trial.
      DESIGN: qualitative study with semi-structured interviews carried out at three
      weeks post partum. Interview transcripts were analysed to identify recurrent
      themes, focusing on why women became involved in the study, their views about
      both the self-medication and the home setting, and whether they would repeat the
      experience. SETTING: the home. PARTICIPANTS: twenty women enrolled in the main
      randomised controlled trial. INTERVENTION: the study is part of a double-blind
      randomised controlled trial with 350 patients investigating whether a nitric
      oxide donor (IMN) used in cervical ripening improves the process of induction of
      labour. FINDINGS: women liked the opportunity to remain at home during the
      cervical ripening process. Timing and setting were central issues; women hoped
      that it would hasten labour, while the home was seen as a setting offering
      freedom, security and reassurance, as opposed to the hospital, seen as
      constraining. Two women reported problems with IMN but the remainder reported
      that they would repeat the experience. IMPLICATIONS FOR PRACTICE: women were very
      positive about the opportunity to undertake cervical ripening at home. It is
      important to explore this setting further for appropriate interventions.

PMID- 20045585
TI  - Arsenic accumulation and phosphorus status in two rice (Oryza sativa L.)
      cultivars surveyed from fields in South China.
AB  - The consumption of paddy rice (Oryza sativa L.) is a major inorganic arsenic
      exposure pathway in S.E. Asia. A multi-location survey was undertaken in
      Guangdong Province, South China to assess arsenic accumulation and speciation in
      2 rice cultivars, one an Indica and the other a hybrid Indica. The results showed
      that arsenic concentrations in rice tissue increased in the order grain < husk <
      straw < root. Rice grain arsenic content of 2 rice cultivars was significant
      different and correlated with phosphorus concentration and molar ratio of P/As in
      shoot, being higher for the Indica cultivar than for the hybrid Indica, which
      suggests altering shoot phosphorus status as a promising route for breeding rice
      cultivars with reduced grain arsenic. Speciation of grain arsenic, performed
      using HPLC-ICP-MS, identified inorganic arsenic as the dominant arsenic species
      present in the rice grain.

PMID- 20045586
TI  - Biomonitoring of traffic-related nitrogen oxides in the Maurienne valley (Savoie,
      France), using purple moor grass growth parameters and leaf (15)N/(14)N ratio.
AB  - Effects of traffic-related nitrogenous emissions on purple moor grass (Molinia
      caerulea (L.) Moench) transplants, used here as a new biomonitoring species, were
      assessed along 500 m long transects orthogonal to roads located in two open areas
      in the Maurienne valley (French Alps). Leaves were sampled during summer 2004 and
      2005 for total N-content and (15)N-abundance determination while nitrogen oxides
      (NO and NO(2)) concentrations were determined using passive diffusion samplers. A
      significant and negative correlation was observed between plant total N-content,
      and (15)N-abundance and the logarithm of the distance to the road axis. The
      strongest decreases in plant N parameters were observed between 15 and 100 m from
      road axis. They were equivalent to background levels at a distance of about 800 m
      from the roads. In addition, motor vehicle pollution significantly affected
      vegetation at road edge, as was established from the relationship between leaf
      (15)N-abundance, total N-content and road traffic densities.

PMID- 20045587
TI  - [Round pneumonia: a rare cause of multiple pulmonary nodes].

PMID- 20045588
TI  - First-trimester prenatal diagnosis performed on pregnant women with fetal
      ultrasound abnormalities: the reliability of interphase fluorescence in situ
      hybridization (FISH) on mesenchymal core for the main aneuploidies.
AB  - OBJECTIVES: To examine the reliability of interphase FISH analysis of the main
      aneuploidies performed on mesenchymal core when prenatal diagnosis was performed
      on pregnant women with first-trimester fetal abnormalities on ultrasound. STUDY
      DESIGN: 386 first-trimester prenatal examinations were investigated from
      chorionic villus samplings for increased nuchal translucencies or other fetal
      ultrasound abnormalities. Interphase fluorescence in situ hybridization (FISH)
      for the main aneuploidies (trisomies 13, 18, 21 and gonosomal aneuploidies) was
      performed on the mesenchymal core of villi. Molecular cytogenetic results were
      always complemented by conventional cytogenetic results on long-term cultured
      villi (LTC-villi). Short-term cultured villi (STC-villi) preparations were
      retrospectively performed only when a chromosomal abnormality was observed with
      interphase FISH and/or LTC-villi. RESULTS: 88 chromosomal abnormalities
      (88/386=22.8% of first-trimester diagnoses) which could discuss subsequent
      abortions were observed after LTC-villi preparations. All cases possibly
      detectable by interphase FISH were detected. Thus, 85 aneuploidies (85/386=22.0%
      of first-trimester diagnoses; 85/88=96.6% of chromosomal abnormalities) were
      detected by interphase FISH, allowing early abortion by curettage before week 14
      amenorrhea. No discrepancy occurred between interphase FISH and LTC-villi results
      for the aneuploidies studied. Three false-negative results (3/386=0.77% of first
      trimester diagnoses; 3/88=3.41% of chromosomal abnormalities) were observed with
      STC-villi. CONCLUSION: We observed a high rate of false-negative results on
      cytotrophoblast cells. Conversely, interphase FISH of the main aneuploidies on
      the mesenchymal core provided rapid and reliable results, and therefore should be
      preferred to STC-villi in first-trimester prenatal diagnosis performed on
      pregnant women with fetal abnormalities on ultrasound.

PMID- 20045589
TI  - Evaluation of the sensitivity of an in vitro high frequency ultrasound device to
      monitor the coagulation process: study of the effects of heparin treatment in a
      murine model.
AB  - This study evaluates the sensitivity of a new in vitro high frequency ultrasound
      test of the whole blood coagulation process. A rat model of anticoagulant
      treatment is reported. Many recent studies of the role of red blood cells in the
      whole blood coagulation process have revealed an increasing demand for global
      tests of the coagulation process performed on whole blood instead of plasma
      samples. In contrast to existing optical tests, high frequency ultrasound
      presents the advantages of characterizing the mechanical properties of whole
      blood clotting. Ultrasound longitudinal wave velocity and integrated attenuation
      coefficient (IAC) were simultaneously assessed in a 10 to 30 MHz frequency range
      during the whole blood coagulation process in vitro in rats under anticoagulant
      therapy. Differences between humans and rats were also clearly emphasized in non
      clotting blood and in clotting blood using specific criteria deduced from
      acoustic parameters (ultrasound velocity for non-clotting blood:=1574+/-2m/s for
      rats and 1583+/-3m/s for humans and IAC=2.25+/-0.14 dB/cm for rats and 1.5+/-0.23
      dB/cm for humans). We also measured the coagulation time t(0) from the acoustic
      velocity (t(0) =11.15+/-7 min for control rat blood and 43.3+/-11.4 min for human
      blood). Different doses of heparin were administered to rats. The sensitivity of
      the ultrasound device to the effects of heparin was evaluated. Differences
      between non-treated rats and chronically and acutely treated rats were recorded
      and quantified. We particularly noted that the slope S and the amplitude I of the
      variations in acoustic velocity were linked to clot retraction, which is a good
      indicator of the platelet function. The amplitude of the variations in S was
      between (20+/-8) x1 0(-3) m/s(2) for control group rats, and (0.92+/-0.35) x 10(
      3) m/s(2) for chronic heparin-treated group rats. The values of I were 15 times
      higher for control group rats than for chronic heparin-treated group rats.

PMID- 20045590
TI  - Transverse acoustic trapping using a gaussian focused ultrasound.
AB  - The optical tweezer has become a popular device to manipulate particles in
      nanometer scales and to study the underlying principles of many cellular or
      molecular interactions. Theoretical analysis was previously carried out at the
      authors' laboratory, to show that similar acoustic trapping of microparticles may
      be possible with a single beam ultrasound. This article experimentally presents
      the transverse trapping of 125 microm lipid droplets under an acoustically
      transparent mylar film, which is an intermediate step toward achieving acoustic
      tweezers in three-dimension. Despite the lack of axial trapping capability in the
      current experimental arrangement, it was found that a 30 MHz focused beam could
      be used to laterally direct the droplets toward the focus. The spatial range
      within which acoustic traps may guide droplet motion was in the range of hundreds
      of micrometers, much greater than that of optical traps. This suggests that this
      acoustic device may offer an alternative for manipulating microparticles in a
      wider spatial range.

PMID- 20045591
TI  - Evaluation of short-axis and long-axis myocardial function with two-dimensional
      strain echocardiography in patients with different degrees of coronary artery
      stenosis.
AB  - This study was designed to characterize the changes in the peak systolic
      longitudinal, circumferential and radial strains by using 2-D strain
      echocardiography in patients with coronary artery stenosis without segmental wall
      motion abnormalities on conventional 2-D echocardiography. 2D strain
      echocardiography was performed in 44 patients with different degrees of coronary
      artery stenosis. Myocardial longitudinal, circumferential and radial strain
      profiles were obtained and peak systolic strain values were measured. The peak
      systolic longitudinal strain was significantly reduced in myocardial segments
      subtended by coronary arteries with greater than 75% stenosis when compared with
      those subtended by coronary artery with less than 75% stenosis and those in
      control. Sensitivity and specificity were 74% and 72%, respectively, for peak
      systolic longitudinal strain to predict segments subtended by coronary arteries
      with greater than 75% stenosis (cutoff value--17.7%; area under the receiver
      operating characteristic curve, 0.825). There were no significant differences in
      circumferential and radial strains among myocardial segments subtended by
      coronary arteries with greater than 75% stenosis and those with less than 75%
      stenosis and in control. In conclusion, our study suggests that analysis of long
      axis cardiac function by using the 2-D strain echocardiography may help to
      identify the myocardial segments subtended by coronary arteries with severe
      stenosis.

PMID- 20045592
TI  - Investigation of the relationship of nonlinear backscattered ultrasound intensity
      with microbubble concentration at low MI.
AB  - The aim of this study was to measure the relationship of image intensity with
      contrast agent concentration. In vitro experiments were performed with a flow
      phantom and a sulphur hexafluoride filled microbubble contrast agent (SonoVue) at
      different concentrations (0.004 per thousand to 4 per thousand) covering the
      range commonly encountered in clinical practice. The concentration of
      microbubbles in the contrast agent solutions was confirmed optically. Images were
      collected with a diagnostic ultrasound system (iU22, Phillips Medical Systems,
      Bothell, WA, USA) and with a nonlinear imaging technique (power modulation) at
      low mechanical index (MI=0.05) to avoid bubble destruction. The mean intensity
      within a region of interest was measured to produce time-intensity curves from
      linearized (absolute scale) data. The relationship of linearized image intensity
      to contrast agent concentration was found to be linear up to 1 per thousand and
      reached a plateau at approximately 2 per thousand. To operate in the linear range
      of the intensity-concentration relationship the contrast agent dose should be
      adjusted to avoid those high values in vivo and the highest dynamic range of the
      ultrasound system should be used to avoid unnecessary signal saturation.

PMID- 20045593
TI  - Dynamic cerebral autoregulation in the old using a repeated sit-stand maneuver.
AB  - The aim of this study was to assess the feasibility and reproducibility of a
      simple and nonobtrusive repeated sit-stand maneuver to assess cerebral
      autoregulation (CA) in healthy old subjects >70 years. In 27 subjects aged 76 (SD
      4) years, we continuously measured blood pressure using photoplethysmography and
      cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler
      ultrasonography) during 5 min of sitting rest and again during repeated sit-stand
      maneuvers at 10 s (0.05 Hz) and 5 s (0.1 Hz) intervals. In 11 randomly selected
      subjects, these measurements were repeated after 3 months. Both maneuvers induced
      substantial periodic oscillations in pressure and flow. For example, the
      maneuvers at 0.05 Hz increased the power spectral density (magnitude) of blood
      pressure and cerebral blood flow velocity oscillations with 16.3 (mm Hg)(2) and
      14.5 (cm/s)(2), respectively (p<0.001). These larger oscillations led to an
      increase in transfer function coherence compared with spontaneous oscillations
      from 0.46 to 0.60 for 0.05 Hz maneuvers and from 0.56 to 0.76 for 0.1 Hz
      maneuvers (p<0.01), allowing for more confident assessment of CA through transfer
      function phase and gain. This increased coherence was not associated with
      improved reproducibility however. In conclusion, we were able to investigate CA
      in old patients using these repeated sit-stand maneuvers, which, compared with
      spontaneous oscillations, produced a stronger and more clinically relevant
      hemodynamic challenge for CA.

PMID- 20045594
TI  - RNA polymerase - an important molecular target of triptolide in cancer cells.
AB  - Triptolide, a diterpenoid triepoxide, is the key biological component of
      Tripterygium wilfordii Hook. f. which was used in traditional Chinese medicine
      for centuries to treat inflammation and autoimmune diseases. Triptolide has shown
      potent activity in not only anti-inflammation and immune modulation, but also
      antiproliferative and proapoptotic activity in many different types of cancer
      cells. However, for a long time, the precise molecular target(s) of triptolide
      have remained elusive. Recently, several groups discovered that triptolide
      inhibited the activity of RNA polymerase. This review will focus on these
      breakthrough findings about the molecular target of triptolide and its
      implications for targeted-cancer therapeutics.

PMID- 20045595
TI  - Hospitalised hot tap water scald patients following the introduction of
      regulations in NSW, Australia: who have we missed?
AB  - Scalds from hot tap water are serious injuries that are potentially preventable
      by restricting the temperature of hot tap water delivery. In July 1999,
      regulations were introduced in NSW to require that all new hot water
      installations deliver water at temperatures not exceeding 50 degrees C to
      sanitary fixtures. This study investigates trends in hot tap water scald injury
      hospitalisations following the introduction of these regulations. Hot tap water
      scald cases for 1999-2007 were identified from hospitalisation data for all
      public and private hospitals in NSW. To investigate hot tap water scald
      hospitalisations over time, negative binomial regression analysis was performed.
      There were 845 hospitalisations for hot tap water scalds in NSW over the period
      of the study. Hospital admission rates for hot tap water scalds decreased by an
      estimated 6% (3.2-8.5, 95%CI) per year since the introduction of regulations.
      While those most at risk were infants, toddlers and the elderly, almost a third
      of hospitalisations were for adults (25-64 years). The majority of hot tap water
      scalds were sustained at home and a further 4% occurred in a residential
      institute or school. The majority of scalds were severe, and a quarter required
      admission for longer than a week. The introduction of regulations in NSW appears
      to have had a positive impact on the rates of hospitalisations for hot tap water
      scalds; however, scalds continue to cause significant morbidity and mortality.
      This highlights the need for a review of the scope and implementation of the
      existing regulations and ongoing education of the general public to the dangers
      of hot tap water.

PMID- 20045596
TI  - Endocrine system dynamics and MS epidemiology.
AB  - In the kidney there is a co-transport relationship in the nephron between the
      reabsorption of positive Na(+) ions and the reabsorption of negative ions such as
      uric acid anions. Uric acid acts as an anti-oxidant and it has been shown to have
      a sealing effect on the blood-brain barrier. The theory developed here is that
      chronic neurological vasoconstriction in cool environmental conditions injects an
      offset into the rennin-angiotensin-aldosterone system (RAAS) blood pressure
      control loop and reduces demand for angiotensin and aldosterone. (Aldosterone is
      produced in the adrenal gland and has a direct effect on renal reabsorption of
      Na(+) ions.) Via co-transport these conditions will reduce the body's ability to
      reabsorb uric acid and this in turn will weaken the integrity of the blood-brain
      barrier. Also, in cool environments, where levels of vasopressin (ADH) and
      aldosterone are lower, the gain of the hypothalamus-pituitary-adrenal gland (HPA)
      axis is reduced so that the production average levels of ACTH, cortisone and
      aldosterone will be biased at a lower level and the kidney-local levels of
      aldosterone in particular will remain lower. This paper develops these ideas and
      suggests that they can help explain the traditionally-recognized latitudinal
      gradient in MS epidemiology. Also, acclimatization to heat encourages sweating,
      which should create a greater demand for the renal reabsorption of Na(+) ions
      which enables greater reabsorption of uric acid. Therefore people living at low
      latitudes should have a lower chance of hypouricemia and a lower chance of
      developing MS. In fact people who spend their first fifteen years in the tropics
      almost never go onto develop MS. And MS patients in relapse are consistently
      hypouricemic. This hypothesis can explain both of these facts. The paper goes
      onto show how the MS condition will tend to progress because of a number of self
      sustaining effects: over time the immune system becomes more targeted to myelin,
      MS patients are unlikely to become acclimatized to heat because they tend to
      avoid heat since demyelinated nerve function is worsened by elevated temperature,
      and the normal circadian excitation of the HPA axis gets weaker under the benign
      environmental conditions typically adopted by MS patients as the disease
      develops.

PMID- 20045597
TI  - Dimensionality of DSM-IV nicotine dependence in a national sample: an item
      response theory application.
AB  - BACKGROUND: Research focusing on the development of a dimensional representation
      of DSM-IV nicotine dependence is scarce and prior research has not assessed the
      role of nicotine use criteria in that a dimensional representation, nor the
      invariance of the DSM-IV nicotine dependence criteria across important population
      subgroups. METHODS: Using a large, representative sample of the U.S. population,
      this study utilized item response theory (IRT) analyses to explore the
      dimensionality of DSM-IV nicotine dependence criteria and several candidate
      criteria for cigarette use among past-year cigarette smokers (n=10,163). RESULTS:
      Factor analyses demonstrated the unidimensionality of nicotine dependence
      criteria and IRT analyses demonstrated good fit of the observed responses and the
      underlying, unobserved latent trait of dependence severity. The model containing
      all seven DSM-IV dependence criteria, along with the consumption criterion of
      smoking at least a quarter of a pack of cigarettes in a day in the past year, was
      identified as the best-fitting model. No differential criterion functioning was
      shown across sex, race-ethnicity, and age subgroups. DISCUSSION: Major
      implications of this study are discussed in terms of the addition of a
      dimensional representation of nicotine dependence to pre-existing categorical
      representations of the disorder in the DSM-V, and the need for a nicotine
      consumption criterion to improve representations of nicotine dependence severity.

PMID- 20045598
TI  - Ancient schwannoma of the nasal septum associated with sphenoid sinus mucocele.
AB  - Schwannoma is a benign tumor arising from the sheath of myelinated nerve fibers
      and may occur in any part of the body. Ancient schwannoma, a variant of
      schwannomas, in the head and neck region is uncommon, and its occurrence in the
      nasal cavity and paranasal sinuses is extremely rare with only one case reported
      to date. Herein, we describe a rare case of sinonasal ancient schwannoma. The
      tumor arose from the nasal septum and extended to the sphenoid sinus. It was
      successfully treated by endoscopic sinus surgery, and the patient showed no
      evidence of recurrence 24 months postoperatively.

PMID- 20045599
TI  - Initial in vivo rodent sodium and proton MR imaging at 21.1 T.
AB  - The first in vivo sodium and proton magnetic resonance (MR) images and localized
      spectra of rodents were attained using the wide bore (105 mm) high resolution
      21.1-T magnet, built and operated at the National High Magnetic Field Laboratory
      (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats
      (approximately 250 g) were acquired with custom designed radiofrequency probes at
      frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging
      resolutions of approximately 0.125 microl for mouse and rat heads were achieved
      by using a 3D back-projection pulse sequence. A gain in SNR of approximately 3
      for sodium and approximately 2 times for proton were found relative to
      corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton
      mouse images (50x50x50 microm(3)) were acquired in 90 min and corresponding rat
      images (100x100x100 microm(3)) within a total time of 120 min. Both in vivo large
      rodent MR imaging and localized spectroscopy at the extremely high field of 21.1
      T are feasible and demonstrate improved resolution and sensitivity valuable for
      structural and functional brain analysis.

PMID- 20045600
TI  - Quantitative SENSE-MRSI of the human brain.
AB  - PURPOSE: To develop a method for estimating metabolite concentrations using
      phased-array coils and sensitivity-encoded (SENSE) magnetic resonance
      spectroscopic images (MRSI) of the human brain. MATERIALS AND METHODS: The method
      is based on the phantom replacement technique and uses receive coil sensitivity
      maps and body-coil loading factors to account for receive B(1) inhomogeneity and
      variable coil loading, respectively. Corrections for cerebrospinal fluid content
      from the MRSI voxel were also applied, and the total protocol scan time was less
      than 15 min. The method was applied to 10 normal human volunteers using a
      multislice 2D-MRSI sequence at 3 T, and seven different brain regions were
      quantified. RESULTS: N-Acetyl aspartate (NAA) concentrations varied from 9.7 to
      14.7 mM, creatine (Cr) varied from 6.6 to 10.6 mM and choline (Cho) varied from
      1.6 to 3.0 mM, in good general agreement with prior literature values.
      CONCLUSIONS: Quantitative SENSE-MRSI of the human brain is routinely possible
      using an adapted phantom-replacement technique. The method may also be applied to
      other MRSI techniques, including conventional phase encoding, with phased-array
      receiver coils, provided that coil sensitivity profiles can be measured.

PMID- 20045601
TI  - A novel biochromatographic Oatp2 column to study the transmembrane transport of
      statins.
AB  - In a previous paper, using a biophysical model system to study the passive
      diffusion of the statin molecules through the cell membrane, our group
      demonstrated that statins could cross biological membrane by passive diffusion
      (Sarr et al. [40]). However, in the liver, the uptake of statins would also be
      mediated by organic anion transporting polypeptides (Oatps) like Oatp2 a member
      of this family. Thus, a novel biochromatographic approach was developed in our
      laboratory to study the transmembrane transport of statins and an Oatp2 inhibitor
      via this carrier family. For this, the Oatp2 protein was immobilized via its
      amino groups on a chromatographic support using an "in situ" immobilization
      technique. For the first time, using this novel biochromatographic concept, the
      effect of magnesium chloride salt (MgCl(2)) on the pharmacomolecule-Oatp2 binding
      was investigated. It was shown an Mg(2+)-dependent pharmacomolecule-protein
      association and a potential facilitated diffusion of these pharmacomolecules into
      biological membrane. This association process was due to the central positive
      potential pore of the Oatp2. Indeed, at pH 7.4, all the pharmacomolecules studied
      were ionized (i.e. negatively charged) and so interact with this positive
      potential pore. However, an increase of the Mg(2+) concentration led a decrease
      of the pharmacomolecule-Oatp2 association attributed to ion pair formations
      between the Mg(2+) cation and molecules. Moreover, the decrease of this affinity
      could be explained by an ion attraction between the Cl(-) anion of the MgCl(2)
      salt and the positively charged pore of the protein. This novel
      biochromatographic column could be useful to find a specific reversible inhibitor
      for these transporters and so open new perspectives to be investigated.

PMID- 20045602
TI  - Pseudoaneurysm of an arteriovenous dialysis graft.

PMID- 20045603
TI  - "Cord sign" in deep cerebral venous thrombosis.

PMID- 20045604
TI  - Human health hazards of veterinary medications: information for emergency
      departments.
AB  - BACKGROUND: There are over 5000 approved prescription and over-the-counter
      medications, as well as vaccines, with labeled indications for veterinary
      patients. Of these, there are several products that have significant human health
      hazards upon accidental or intentional exposure or ingestion in humans:
      carfentanil, clenbuterol (Ventipulmin), ketamine, tilmicosin (Micotil),
      testosterone/estradiol (Component E-H and Synovex H), dinoprost
      (Lutalyse/Prostamate), and cloprostenol (Estromate/EstroPlan). The hazards range
      from mild to life-threatening in terms of severity, and include bronchospasm,
      central nervous system stimulation, induction of miscarriage, and sudden death.
      OBJECTIVE: To report medication descriptions, human toxicity information, and
      medical management for the emergent care of patients who may have had exposure to
      veterinary medications when they present to an emergency department (ED).
      DISCUSSION: The intended use of this article is to inform and support ED
      personnel, drug information centers, and poison control centers on veterinary
      medication hazards. CONCLUSION: There is a need for increased awareness of the
      potential hazards of veterinary medications within human medicine circles. Timely
      reporting of veterinary medication hazards and their medical management may help
      to prepare the human medical community to deal with such exposures or abuses when
      time is of the essence.

PMID- 20045605
TI  - The relationship of radiocontrast, iodine, and seafood allergies: a medical myth
      exposed.
AB  - BACKGROUND: Radiocontrast agents are some of the most commonly used medications
      in the emergency department. However, both physicians and patients misunderstand
      the role that allergies play in reactions to radiocontrast media, especially with
      regards to shellfish and iodine. OBJECTIVES: We sought to review the literature
      describing rates of contrast reactions and risk of contrast administration to
      patients with iodine allergy, shellfish or seafood allergies, or prior reactions
      to intravenous iodinated contrast. METHOD: Both authors independently performed
      literature reviews, including position statements of stakeholder organizations,
      to gain perspective on important issues. They subsequently performed a systematic
      search for articles that estimated the risk of administration of iodinated
      contrast to those with a prior history of contrast reaction, "iodine allergy," or
      reaction to seafood or shellfish. RESULTS: The risk of reactions to contrast
      ranges from 0.2-17%, depending on the type of contrast used, the severity of
      reaction considered, and the prior history of any allergy. The risk of reaction
      in patients with a seafood allergy is similar to that in patients with other food
      allergies or asthma. A history of prior reaction to contrast increases the risk
      of mild reactions to as high as 7-17%, but has not been shown to increase the
      rate of severe reactions. Severe reactions occur in 0.02-0.5% and deaths in
      0.0006-0.006%; neither have been related to "iodine allergy," seafood allergy, or
      prior contrast reaction. Low-osmolality contrast media became available in 1988,
      and many of the higher risk estimates were from the era before it was widely
      available. CONCLUSIONS: Iodine is not an allergen. Atopy, in general, confers an
      increased risk of reaction to contrast administration, but the risk of contrast
      administration is low, even in patients with a history of "iodine allergy,"
      seafood allergy, or prior contrast reaction. Allergies to shellfish, in
      particular, do not increase the risk of reaction to intravenous contrast any more
      that of other allergies.

PMID- 20045606
TI  - Encounters with venomous sea-life.
AB  - BACKGROUND: Sea-life with envenomation capabilities are quite abundant and
      diverse worldwide, being predominantly found in tropical waters. Most
      envenomations occur not as an attack, but as a result of self defense when the
      animal perceives danger; and often when locals or tourists are engaged in
      recreational activities. Most of these cases have only minor injuries, and few
      are fatal. OBJECTIVES: To describe the impact, clinical features, and management
      of life-threatening marine envenomations. DISCUSSION: Recognition of the injury
      and identification of the responsible animal is crucial for quick and successful
      management. Medical professionals should be cognizant of presenting symptoms such
      as respiratory distress, muscle paralysis, or cardiovascular decompensation. For
      these patients, antivenom should be given immediately if available, followed by
      pharmacological and physical therapy to relieve symptoms and pain. If any foreign
      bodies are left at the site of the injury, they must be removed. Tetanus
      prophylaxis should also be considered in case of puncture, and if signs of early
      infection are present, broad-spectrum antibiotics should be administered.
      CONCLUSION: Management of envenomations from marine animals should be emphasized
      not only to health centers, but also to the general population, so that initial
      treatment can be started as soon as possible. Educational programs regarding
      risks and initial management for these incidents are also recommended to reduce
      the incidence and associated morbidity and mortality of the encounters.

PMID- 20045607
TI  - Ability of physicians to diagnose congestive heart failure based on chest X-ray.
AB  - BACKGROUND: Chest X-ray interpretation is an important skill in the diagnosis of
      congestive heart failure (CHF) by emergency physicians. OBJECTIVES: This study
      evaluated the ability of emergency physicians to recognize CHF on chest X-ray and
      the effect of level of training and confidence upon accuracy of interpretation.
      METHODS: This was a prospective, blinded study in which 24 patients with an
      elevated brain natriuretic peptide, low ejection fraction, and diagnosis of CHF
      were retrospectively identified. In addition, 31 patients without CHF were
      identified and used as controls. These 55 chest X-rays were presented to
      emergency attending and housestaff and a radiologist. We calculated the accuracy
      of the raters' diagnoses, and measured their confidence in that diagnosis and
      their level of training. RESULTS: Physicians correctly identified the CHF chest X
      rays 79% of the time (sensitivity 59%, specificity 96%; positive likelihood ratio
      14.6, negative likelihood ratio 0.43). Accuracy ranged from a low of 78% among
      first-year residents to a high of 85% among attending, and from 73% (confidence
      rating of 3/5) to 91% (confidence rating of 5/5). Increasing confidence was
      significantly correlated with accuracy across the spectrum (p = 0.001). An
      accuracy of 95% among radiologists suggests that a negative X-ray does not rule
      out CHF. CONCLUSIONS: High specificity (96%) and low sensitivity (59%) suggest
      that emergency physicians are excellent at identifying CHF on X-ray when present,
      but under-call it frequently. Sensitivity may be much higher in real life given
      clinical correlation. Both increased level of training and higher confidence
      significantly improved accuracy.

PMID- 20045608
TI  - Abdominal palpation with Ou MC manipulation (APOM) for women with acute abdomen
      caused by pelvic inflammatory disease: a pilot study.

PMID- 20045609
TI  - Protamine reduces bleeding complications associated with carotid endarterectomy
      without increasing the risk of stroke.
AB  - OBJECTIVES: Controversy persists regarding the use of protamine during carotid
      endarterectomy (CEA) based on prior conflicting reports documenting both reduced
      bleeding as well as increased stroke risk. The purpose of this study was to
      determine the effect of protamine reversal of heparin anticoagulation on the
      outcome of CEA in a contemporary multistate registry. METHODS: We reviewed a
      prospective regional registry of 4587 CEAs in 4311 patients performed by 66
      surgeons from 11 centers in Northern New England from 2003-2008. Protamine use
      varied by surgeon (38% routine use, 44% rare use, 18% selective use). Endpoints
      were postoperative bleeding requiring reoperation as well as potential thrombotic
      complications, including stroke, death, and myocardial infarction (MI).
      Predictors of endpoints were determined by multivariate logistic regression after
      associated variables were identified by univariate analysis. RESULTS: Of the 4587
      CEAs performed, 46% utilized protamine, while 54% did not. Fourteen patients
      (0.64%) in the protamine-treated group required reoperation for bleeding compared
      with 42 patients (1.66%) in the untreated cohort (P = .001). Protamine use did
      not affect the rate of MI (1.1% vs 0.91%, P = .51), stroke (0.78% vs 1.15%, P =
      .2), or death (0.23% vs 0.32%, P = .57) between treated and untreated patients,
      respectively. By multivariate analysis, protamine (odds ratio [OR] 0.32, 95%
      confidence interval [CI], 0.17-0.63; P = .001) and patch angioplasty (OR 0.46,
      95% CI, 0.26-0.81; P = .007) were independently associated with diminished
      reoperation for bleeding. A single center was associated with a significantly
      higher rate of reoperation for bleeding (OR 6.47, 95% CI, 3.02-13.9; P < .001).
      Independent of protamine use, consequences of reoperation for bleeding were
      significant, with a four-fold increase in MI, a seven-fold increase in stroke,
      and a 30-fold increase in death. CONCLUSION: Protamine reduced serious bleeding
      requiring reoperation during CEA without increasing the risk of MI, stroke, or
      death, in this large, contemporary registry. In light of significant
      complications referable to bleeding, liberal use of protamine during CEA appears
      warranted.

PMID- 20045610
TI  - A portable high-intensity focused ultrasound device for noninvasive venous
      ablation.
AB  - BACKGROUND: Varicose veins and other vascular abnormalities are common clinical
      entities. Treatment options include vein stripping, sclerotherapy, and endovenous
      laser treatment, but all involve some degree of invasive intervention. The
      purpose of this study was to determine ex vivo the effectiveness of a novel hand
      held, battery-operated, high-intensity focused ultrasound (HIFU) device for
      transcutaneous venous ablation. METHODS: The ultrasound device is 14 x 9 x 4 cm,
      weighs 650 g, and is powered by 4 lithium ion battery packs. An ex vivo testing
      platform consisting of two different models comprised of sequentially layered
      skin-muscle-vein or skin-fat-vein was developed, and specimens were treated with
      HIFU. The tissues were then disassembled, imaged, and processed for histology.
      The luminal cross-sectional area of vein that had been treated with HIFU and
      nontreated controls were measured, and the values presented as median and
      interquartile range (IQR). The values were compared using a Wilcoxon rank-sum
      test, and statistical significance was set at P < .05. RESULTS: On gross and
      histologic examination, veins that had been treated with HIFU showed evidence of
      coagulation necrosis. The surface of the muscle in direct contact with the vein
      had a pinpoint area of coagulation, whereas the adjacent fat appeared
      undisturbed; the skin, fat, and the surface of the muscle in contact with the
      transducer remained completely unaffected. The cross-sectional area was 3.79
      mm(2) (IQR, 3.38-4.22) of the control vein lumen and 0.16 mm(2) (IQR, 0.04-0.39)
      in those that had been treated with HIFU (P = .0304). CONCLUSION: This
      inexpensive, portable HIFU device has the potential to allow clinicians to easily
      perform venous ablation in a manner that is entirely noninvasive and without the
      expense or inconvenience of large, complicated devices. This device represents a
      significant step forward in the development of new applications for HIFU
      technology.

PMID- 20045611
TI  - The influence of different sub-bandage pressure values on venous leg ulcers
      healing when treated with compression therapy.
AB  - BACKGROUND: Venous leg ulcers (VLU) have a huge social and economic impact. An
      estimated 1.5% of European adults will suffer a venous ulcer at some point in
      their lives. Despite the widespread use of bandaging with high pressure in the
      treatment of this condition, recurrence rates range between 25% to 70%. Numerous
      studies have suggested that the compression system should provide sub-bandage
      pressure values in the range from 35 mm Hg to 45 mm Hg in order to achieve the
      best possible healing results. METHODS: An open, randomized, prospective, single
      center study was performed in order to determine the healing rates of VLU when
      treated with different compression systems and different sub-bandage pressure
      values. One hundred thirty-one patients (72 women, 59 men; mean age, 59-years
      old) with VLU (ulcer surface >3 cm(2); duration >3 months) were randomized into
      three groups: group A - 42 patients who were treated using an open-toed, elastic,
      class III compression device knitted in tubular form (Tubulcus, Laboratoires
      Innothera, Arcueil, France); group B - 46 patients treated with the multi
      component bandaging system comprised of Tubulcus and one elastic bandage (15 cm
      wide and 5 cm long with 200% stretch, Niva, Novi Sad, Serbia); and group C -
      forty-three patients treated with the multi-component bandaging system comprised
      of Tubulcus and two elastic bandages. Pressure measurements were taken with the
      Kikuhime device (TT MediTrade, Soro, Denmark) at the B1 measuring point in the
      supine, sitting, and standing positions under the three different compression
      systems. RESULTS: The median resting values in the supine and standing positions
      in examined study groups were as follows: group A - 36.2 mm Hg and 43.9 mm Hg;
      group B - 53.9 mm Hg and 68.2 mm Hg; group C - 74.0 mm Hg and 87.4 mm Hg. The
      healing rate during the 26-week treatment period was 25% (13/42) in group A,
      67.4% (31/46) in group B, and 74.4% (32/43) in group C. The success of
      compression treatment in group A was strongly associated with the small ulcer
      surface (<5 cm(2)) and smaller calf circumference (CC; <38 cm). On the other
      hand, compliance in group A was good. In groups B and C, compliance was poor in
      patients with small CC, but the healing rate was high, especially in patients
      with large ulcers and a large CC (>43 cm). CONCLUSION: The results obtained in
      this study indicate that better healing results are achieved with two or multi
      component compression systems than with single-component compression systems and
      that a compression system should be individually determined for each patient
      according to individual characteristics of the leg and CC. Target sub-bandage
      pressure value (B1 measuring point in the sitting position) of the compression
      system needed for the ulcer healing could be determined according to a simple
      formula, CC + CC/2.

PMID- 20045612
TI  - Collateral pathways visualization of the innominate vein.

PMID- 20045613
TI  - Endovascular repair of popliteal aneurysms.
AB  - Endovascular repair is an established modality of treatment for abdominal aortic
      aneurysms. It is therefore reasonable to expect its application to other less
      common aneurysmal conditions, including isolated iliac and popliteal artery
      aneurysms (PAA). There are, however, essential differences between aortic
      aneurysms and peripheral aneurysms: smaller arterial caliber, mobility of the
      arterial segment, associated occlusive disease, and devices that have not been
      specifically designed for peripheral applications. Due to these differences,
      results obtained in abdominal aortic aneurysms cannot be extrapolated to
      peripheral aneurysms. The attraction of the endovascular repair for PAA is its
      minimally invasive nature. The literature, however, provides only case reports,
      case series and small cohorts, and one small randomized, controlled trial. A
      cumulative summary of these studies provides the clinician with information upon
      which to base the choice of treatment on a specific patient. Endovascular repair
      for PAA with suitable anatomy and good run-off can be considered safe, and medium
      term results appear comparable with those of open repair.

PMID- 20045614
TI  - Comparative study on carotid revascularization (endarterectomy vs stenting) using
      markers of cellular brain injury, neuropsychometric tests, and diffusion-weighted
      magnetic resonance imaging.
AB  - OBJECTIVE: Subclinical alterations of cerebral function can occur during or after
      carotid revascularization and can be detected by a variety of standard tests.
      This comparative study assessed the relationship among serum levels for two
      biochemical markers of cerebral injury, postoperative diffusion-weighted magnetic
      resonance imaging (DW-MRI), and neuropsychometric testing in patients undergoing
      carotid endarterectomy (CEA) or carotid artery stenting (CAS) for high-grade
      asymptomatic carotid stenosis. METHODS: Forty-three consecutive asymptomatic
      patients underwent carotid revascularization by endarterectomy (CEA, 20) or
      stenting (CAS, 23). They were evaluated with DW-MRI and the Mini-Mental State
      Examination (MMSE) test preoperatively and <or=24 hours after carotid
      revascularization. Venous blood samples to assess serum levels of neuron-specific
      enolase (NSE) and S100beta protein were collected for each patient preoperatively
      and five times in a 24-hour period postoperatively and assayed using automated
      commercial equipment. The MMSE test was repeated at 6 months. The relationship
      between serum marker levels and neuropsychometric and imaging tests and
      differences between the two groups of patients were analyzed by chi(2) test, with
      significance at P < .05. RESULTS: No transient ischemic attacks or strokes were
      clinically observed. CAS caused more new subcortical lesions at postoperative DW
      MRI and a significant decline in the MMSE postoperative score compared with CEA
      (P = .03). In CAS patients, new lesions at DW-MRI were significantly associated
      with a postoperative MMSE score decline >5 points (P = .001). Analysis of
      S100beta and NSE levels showed a significant increase at 24 hours in CAS patients
      compared with CEA patients (P = .02). The MMSE score at 6 months showed a
      nonsignificant increase vs the postoperative score in both groups. CONCLUSIONS:
      Biochemical markers measurements of brain damage combined with neuropsychometric
      tests and DW-MRI can be used to evaluate silent injuries after CAS. The
      mechanisms of rise in S100beta and NSE levels at 24 hours after CAS may be due to
      increased perioperative microembolization rather than to hypoperfusion. Further
      studies are required to assess the clinical significance of those tests in
      carotid revascularization.

PMID- 20045615
TI  - Systematic review on the association between calcification in carotid plaques and
      clinical ischemic symptoms.
AB  - OBJECTIVE: The association between carotid plaque calcification and clinical
      ischemic events is unclear. The aim of this study was to systematically review
      published studies comparing degree of calcification between clinically
      symptomatic and asymptomatic plaques. METHODS: A systematic search for relevant
      studies was performed in the PubMed/MEDLINE and Embase databases. For studies
      reporting a rating scale or a continuous measure of calcification, study-specific
      and pooled standardized mean differences (SMDs) between symptomatic and
      asymptomatic plaques were calculated. For studies reporting a dichotomous
      measure, study-specific and pooled odds ratios (ORs) were calculated. If no
      significant heterogeneity was present (I(2) <or=50%), a fixed-effects pooling
      model was used. If significant heterogeneity was present (I(2) >50%), a random
      effects pooling model was used, and sources of heterogeneity were explored by
      subgroup analyses. RESULTS: The 24 studies included in this systematic review
      used a wide range of methodologies to quantify degree of calcification and a wide
      range of definitions to define clinically symptomatic and asymptomatic carotid
      plaques. Pooled fixed-effects SMD of calcification volume or weight between
      symptomatic and asymptomatic plaques was -0.425 (95% confidence interval [CI], 
      0.608 to -0.241); I(2) = 39.3%. Pooled random-effects SMD of calcification
      percentage was -0.997 (95% CI, -1.793 to -0.200); I(2) = 93.8. Subgroup analyses
      did not reveal homogeneous subgroups. Pooled fixed-effects OR for the association
      between high degree of plaque calcification and symptoms was 0.696 (95% CI, 0.528
      to 0.918); I(2) = 21.1%. CONCLUSION: The results of this systematic review
      suggest that clinically symptomatic plaques have a lower degree of calcification
      than asymptomatic plaques. Assessment of degree of carotid plaque calcification
      may be useful to predict which plaques will cause cerebrovascular ischemic
      events.

PMID- 20045616
TI  - Successful repair of a ruptured Stanford type B aortic dissection during
      pregnancy.
AB  - We present our experience with an acute Stanford type B aortic dissection in a 25
      year-old, 26-week gravid patient without a known connective tissue disorder and
      discuss a literature-based treatment strategy. After failed conservative
      treatment manifest by aneurysm rupture, emergency cesarean section delivery and
      immediate repair of her thoracic aorta was performed. Seven months later, she is
      fully caring for her healthy baby. During pregnancy, thoracic aortic dissection
      occurs from physiologic and hemodynamic changes. Emergency cesarean delivery,
      followed by immediate aortic repair, is the treatment choice if malperfusion
      syndrome, rupture, uncontrolled hypertension, or unremitting pain occurs.

PMID- 20045617
TI  - Bullous pemphigoid presenting as dry gangrene in a revascularized limb.
AB  - Bullous pemphigoid (BP) is the most common autoimmune blistering disease, and has
      been associated with many diseases; most autoimmune. It has never previously been
      associated with a reperfused limb. A 74-year-old female underwent a right
      femoroanterior tibial polytetrafluoroethylene (PTFE) bypass for tissue loss and
      rest pain in the right foot. After surgery she was treated for recurrent
      infection which exacerbated tissue loss and was eventually diagnosed as BP. There
      was a delay in diagnosis due to the similarity to dry gangrene. This case
      highlights the potential difficulties of BP diagnosis in a revascularized limb
      and the importance of multidisciplinary management of atypical infection.

PMID- 20045618
TI  - An analysis of the outcomes of a decade of experience with lower extremity
      revascularization including limb salvage, lengths of stay, and safety.
AB  - BACKGROUND: Demographic and practice modality changes during the past decade have
      led to a substantial shift in the management of peripheral vascular disease. This
      study examined the effect of these changes using large national and regional data
      sets on procedure type, indications, morbidity, and on the primary target
      outcome: limb salvage. METHODS: National Inpatient Sample (NIS) data sets and New
      York (NY) State inpatient hospitalizations and outpatient surgeries discharge
      databases from 1998 through 2007 were used to identify hospitalizations for lower
      extremity revascularization (LER) and major amputations. Patients were selected
      by cross-referencing diagnostic and procedural codes. Proportions were analyzed
      by chi(2) analysis, continuous variables by t test, and trends by the Poisson
      regression. RESULTS: The national per capita (100,000 population, age >40 years)
      volume of major amputations decreased by 38%. The volume for national and
      regional use of endovascular LER doubled. The volume of open LER decreased by 67%
      from 1998 through 2007. Ambulatory endovascular LER grew in NY State from 7 per
      capita in 1998 to 22 in 2007. Interventions declined by 20% (93 to 75) for
      critical limb ischemia (CLI) but increased by nearly 50% for claudication.
      Outpatient data analysis revealed a fivefold increase in vascular interventions
      for CLI and claudication. Nationally, endovascular LER interventions quadrupled
      (8% to 32%) for CLI and doubled (26% to 61%) for claudication. A parallel
      reduction occurred in major amputations for patients with CLI (42% to 30%), for
      other PAD diagnoses (18% to 14%), and for claudication (0.9% to 0.3%). Although
      surgical interventions for CLI declined significantly for octogenarians from 317
      to 240, outpatient interventions increased for CLI, claudication, and other
      diagnoses in all age groups. Comorbidities for patients treated in 2006 were
      substantially greater than those of a decade ago. For most procedures, cardiac
      and bleeding complications have significantly decreased during the last decade.
      Length of stay (LOS) declined from 9.5 to 7.6 days and the percentage of short (1
      2 day) hospitalizations increased from 16% to 35%. CONCLUSION: Although patients
      today, whether treated for claudication or CLI, have more comorbidities, the
      rates of amputation, the procedural morbidity and mortality, and LOS have all
      significantly decreased. Other variables, including changes in medical management
      and wound care, undoubtedly are important, but this change appears to be largely
      due to the widespread and successful use of endovascular LER or to earlier
      intervention, or both, driven by the safety of these techniques.

PMID- 20045619
TI  - Trends and outcomes of endovascular and open treatment for traumatic thoracic
      aortic injury.
AB  - OBJECTIVES: Traumatic thoracic aortic injury (TTAI) is associated with high
      mortality rates. Data supporting thoracic endovascular aortic repair (TEVAR) to
      reduce mortality and morbidity for TTAI is limited to small series and meta
      analyses. In this study, we evaluated the trends and outcomes of open surgery and
      TEVAR for TTAI in New York State. METHODS: All cases of TTAI in New York State
      between 2000 and 2007 were extracted from the New York Statewide Planning and
      Research Cooperative System (SPARCS) database. A diagnosis by International
      Classification of Diseases, 9th Revision coding of TTAI was required for
      inclusion. RESULTS: We identified 328 patients with TTAI who underwent surgical
      repair in New York State between 2000 and 2007; mean age of the cohort was 39.3
      years +/- 18 years; 80% were male. Open repair of TTAI was performed in 79.6% and
      20.4% underwent TEVAR. Open repair was performed for all cases of TTAI until the
      introduction of TEVAR in 2005; TEVAR exceeded the use of open repair for TTAI in
      2006 and 2007. Additional major injuries were present in 71.7% in the open repair
      group vs 91.0% of the TEVAR group (P = .001). The overall in-hospital mortality
      rate for the 8-year period was significantly increased after open repair of TTAI
      compared with TEVAR: 17% vs 6%, (odds ratio [OR] 3.19, 95% confidence interval
      [CI], 1.11-9.23; P = .024). After controlling for the significant covariates,
      TEVAR independently reduced the risk of death following surgical intervention for
      TTAI compared with the open procedure (OR 3.8, 95% CI, 1.28-10.99; P = .010).
      Respiratory complications were the most common postoperative morbidity, and were
      significantly increased after open repair: 38% vs 24% (OR 1.95; 95% CI, 1.05
      3.60; P = .032). There were no significant differences in cardiac complications,
      acute renal failure (ARF), paraplegia, or stroke. Endoleak and distal
      embolization each occurred in 9% of patients after TEVAR. CONCLUSIONS: There has
      been a shift toward endovascular management of patients with TTAI. This change in
      surgical strategy has been associated with less postoperative mortality and fewer
      pulmonary complications in patients suffering from TTAI. TEVAR is associated with
      significant device-related complications.

PMID- 20045620
TI  - Determining who trains vascular surgery fellows in endovascular techniques.
AB  - OBJECTIVES: Vascular surgery training has evolved from a single clinical year
      after general surgery training to a multi-year training program to encompass such
      entities as noninvasive vascular laboratory, office-based procedures, and
      endovascular techniques. Simultaneously, members of the vascular surgery
      community have had to undergo significant training to become facile with
      endovascular techniques. We surveyed vascular surgery trainees on the online
      Vascular Surgery In-Training Examination (VSITE) in 2008 and 2009 to assess who
      trained them in percutaneous techniques. METHODS: Vascular surgery trainees in
      the Independent (2-year) and Integrated (5-year) training programs were asked to
      participate in a survey upon completion of the VSITE in 2008 and 2009. Examinees
      were asked to select whether vascular surgeons, cardiologists, or interventional
      radiologists trained them in carotid angioplasty and stenting (CAS), thoracic
      endografts (TEVAR), endovascular abdominal aortic aneurysm repair (EVAR), renal
      artery intervention, iliac stenting, superficial femoral artery (SFA), and tibial
      artery percutaneous interventions. RESULTS: Survey response rate was 79.6% (191
      of 240). Results of the survey are shown in Table I. In 2009, vascular surgeons
      provided more than 84% of the training to vascular surgery residents. Only six
      respondents had >50% of their percutaneous training with interventional radiology
      and two with cardiologists. CONCLUSION: Vascular surgeons involved in resident
      education have been able to retrain themselves in endovascular techniques such
      that they are now able to provide greater than 80% of the endovascular experience
      to vascular surgery residents.

PMID- 20045621
TI  - The diagnosis, morphological particularities, and surgical technique in a case of
      intravascular leiomyoma extended to the right heart chambers.
AB  - Intravenous leiomyoma is a benign smooth muscle cell tumor of uterine origin that
      may grow into the pelvic veins and the inferior vena cava. It usually affects
      premenopausal women and the majority (90%) are parous. Because cardiac
      involvement is present in up to 10% of cases, it may be misdiagnosed as a primary
      cardiac tumor or a venous thrombus-in-transit. We describe a case of
      intravascular leiomyomatosis with cardiac extension and the morphological
      particularities of the removed tumor.

PMID- 20045622
TI  - Robot-assisted laparoscopic repair of renal artery aneurysms.
AB  - OBJECTIVE: The aim of this article is to report our experience in the repair of
      renal artery aneurysms using robot-assisted surgery. METHODS: Between December
      2002 and March 2009, five women with a mean age of 63.8 years (range, 57-78
      years) underwent robot-assisted laparoscopic repair of renal artery aneurysms by
      the same surgeon at two different institutions, the Department of General
      Surgery, Misericordia Hospital, Grosseto, Italy (three patients) and the Division
      of Minimally Invasive and Robotic Surgery at the University of Illinois, Chicago
      (two patients). The mean size of the lesions was 19.4 mm (range, 9-28 mm). Four
      of the lesions were complex aneurysms involving the renal artery bifurcation. Two
      patients were symptomatic and three had hypertension. In situ repair by
      aneurysmectomy was performed in all cases, followed by revascularization. In
      complex aneurysms, an autologous saphenous vein graft was used for the
      reconstruction. RESULTS: The mean operative time was 288 minutes (range, 170-360
      min) and the estimated surgical blood loss was 100 ml (range, 50-300 ml). Warm
      ischemia time was 10 minutes in the patient treated by aneurysmectomy, followed
      by direct reconstruction. The average warm ischemia time was 38.5 minutes (range,
      20-60 min) for patients treated with saphenous vein graft interposition. The mean
      time to resume a regular diet was 1.6 days (range, 1-2 days). The mean
      postoperative length of hospital stay was 5.6 days (range, 3-7 days). No
      postoperative morbidity was noted. The mean follow-up time for the entire series
      was 28 months (range, 6-48 months). Color Doppler ultrasonography examination
      showed patency in all reconstructed vessels. One patient had stenosis of one of
      the reconstructed branches, which was treated with percutaneous angioplasty.
      CONCLUSIONS: Robot-assisted laparoscopic repair of renal artery aneurysms is
      feasible, safe and effective. The technical advantages of the robotic system
      allows for microvascular reconstruction to be performed using a minimally
      invasive approach, even in complex cases. This approach may also allow for
      improved postoperative recovery and reduce the morbidity correlated with open
      repair of renal artery aneurysms. Although more experience and technical
      refinements are necessary, robot-assisted laparoscopic repair of renal artery
      aneurysms represents a valid alternative to open surgery.

PMID- 20045624
TI  - Long-term outcomes and resource utilization of endovascular versus open repair of
      abdominal aortic aneurysms in Ontario.
AB  - OBJECTIVE: Two large randomized trials showed that elective endovascular aneurysm
      repair (EVAR) had similar all-cause long-term mortality rates but increased costs
      compared with open repair for nonruptured abdominal aortic aneurysms (AAAs).
      Despite these data, the use of EVAR continues to increase in North America.
      Currently, there are very limited adjusted population-based data examining long
      term outcomes and resource utilization. METHODS: All patients who underwent
      elective AAA repair between April 2002 and March 2007 in Ontario were identified
      using data from hospital discharge abstracts. Patients were identified with a
      validated algorithm. A propensity score analysis was used to adjust for treatment
      allocation. Clinical outcomes included time to all-cause death and discharge to a
      nursing home or long-term care facility. Resource utilization outcomes included
      imaging utilization, hospital utilization, and reintervention rates. RESULTS:
      Overall, 6461 patients underwent treatment of nonruptured AAAs, comprising 888
      EVARs and 5573 open repairs. EVAR patients were older and had more comorbidities.
      The adjusted mortality was significantly lower in the EVAR group at 30 days
      (adjusted odds ratio [adj-OR], 0.34; 95% confidence interval [95% CI], 0.20
      0.59), but long-term mortality was similar (adj-OR, 0.95; 95% CI, 0.81-1.05).
      EVAR patients were significantly less likely to be discharged to a nursing home
      or other chronic care facility (adj-OR, 0.55; 95% CI, 0.41-0.74). Imaging
      utilization as well as urgent and vascular readmissions were significantly higher
      in the EVAR group. However, the EVAR group had a significantly shorter length of
      stay and less intensive care unit use for the index hospitalization and decreased
      hospital length of stay during follow-up. There was a trend toward a slightly
      increased risk of reintervention with EVAR (adj-OR, 1.3; 95% CI, 0.98-1.75).
      CONCLUSION: Compared with open repair, EVAR significantly reduced short-term but
      not long-term mortality. The EVAR patients spent less time in health
      institutions, including long-term care facilities, but underwent more imaging
      studies. Future improvements in EVAR could result in further decreases in
      reinterventions and subsequent radiologic monitoring.

PMID- 20045625
TI  - Variation in the shape and length of the branches of a thoracoabdominal aortic
      stent graft: implications for the role of standard off-the-shelf components.
AB  - PURPOSE: To describe variations in the shape, orientation, and length of the
      branches of multi-branched thoracoabdominal stent grafts. METHOD: The branches
      were constructed in situ by attaching a covered stent (Fluency Plus
      Tracheobronchial Stent Graft; Bard Peripheral Vascular, Tempe, Ariz) to each of
      four caudally-oriented cuffs on custom-made stent grafts. Pre- and postoperative
      computed tomography (CT) scans of 38 consecutively treated patients were analyzed
      using a three-dimensional work station to give the orientation of celiac,
      superior mesenteric, and right renal and left renal orifices relative to the
      centerline of the aorta (planned cuff orientation [PCO]) and relative to the
      centerline of the stent graft (actual vessel orientation [AVO]). The orientation
      of each cuff (actual cuff orientation [ACO]) was also measured relative to the
      centerline of the stent graft. These values were used to assess the degree of
      stent graft malorientation (ACO-PCO), or cuff-to-artery misalignment (ACO-AVO),
      and combined with measurements of branch length to calculate the resulting
      lateral displacement (arc distance [AD]) between each cuff and its corresponding
      arterial orifice and the angle (longitudinal branch angulation [LBA]) between the
      long axis of the branch and the long axis of the aorta, all in the plane of the
      aortic surface. RESULTS: All 136 branches were inserted as intended. None has
      since migrated, disconnected, or kinked. In most cases, stent graft orientation
      was accurate, with a mean ACO-PCO of 18.4 + 12.1 degrees. Cuff-to-artery
      misalignment was correspondingly low, with a mean ACO-AVO of 19.8 + 14.0 degrees.
      More than 30 degrees of misalignment was present in 23.2% of branches, yet only
      9% (n = 12) had an LBA of >30 degrees. CONCLUSION: Moderate degrees of cuff-to
      artery misalignment had no effect on the feasibility of multi-branched stent
      graft insertion.

PMID- 20045626
TI  - Elevated sex steroid hormones in great saphenous veins in men.
AB  - INTRODUCTION: High serum levels of estradiol are associated with clinical
      evidence of varicose veins in women; however, the relationship between serum sex
      steroid hormones and varicose veins in men is unclear. To address this issue,
      serum levels of testosterone, estradiol, and androstenedione were determined in
      the great saphenous (GSV) and cubital veins of men with varicose veins. Messenger
      RNA (mRNA) expression of sex steroid hormones, metabolizing enzymes, and their
      receptors was investigated in tissue samples of leg veins. METHODS: This
      prospective study included 40 men, comprising 20 with varicose veins and reflux
      of the GSV (VM) and 20 with healthy veins (HM). All limbs were assessed by duplex
      ultrasound scanning of selected superficial and deep leg veins. Blood samples
      were taken from the cubital vein and from the GSV. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) analysis for sex steroid
      hormones, their metabolizing enzymes, and receptors in saphenous veins was
      performed in tissue samples of varicose (n = 6) and healthy veins (n = 6).
      RESULTS: The VM group had significantly higher (P < .001) mean levels for serum
      testosterone (44.9 nmol/L; range, 8.8-225.1) and estradiol (242.2 pmol/L; range,
      79-941) in varicose saphenous veins compared with cubital veins (testosterone,
      15.5 nmol/L; range, 8.4-23.3; estradiol, 93.2 pmol/L; range, 31-147). Moreover,
      significantly (P < .001) higher mean serum estradiol levels (133.2 pmol/L; range,
      63-239) were detected in the saphenous veins of the HM group compared with
      cubital veins (88.15 pmol/L; range, 37-153). Both groups had similar blood counts
      and serum androstenedione levels in the upper and lower extremity. Interestingly,
      qRT-PCR revealed that the mRNA expression of 5alpha-reductase type 1, 5alpha
      reductase type 2, 17, 20 lyase, 17beta-hydroxysteroid dehydrogenase (17beta-HSD),
      aromatase and 3beta-HSD type 2, androgen and estrogen receptor 1 was down
      regulated (P < .05) in all samples of varicose veins vs veins obtained from
      healthy men. CONCLUSION: Elevated serum estradiol and testosterone levels were
      detected in men with varicose veins and reflux in the GSV compared with the
      patient's own arm veins. Enzymes and hormonal receptors involved in steroid
      metabolism were down-regulated in patients with GSV reflux and varicose veins,
      suggestive of a negative feedback regulation. These data support the notion of a
      possible causal relationship between sex steroids and varicose veins in men.

PMID- 20045627
TI  - Usefulness of factor II and factor X as therapeutic markers in patients under
      chronic warfarin therapy.
AB  - Oral anticoagulation with warfarin is a widely used form of treatment for an
      increasing number of medical conditions. Nevertheless, appropriate therapeutic
      monitoring and dosage readjustments should be carried out in order to ensure its
      safety and efficacy. Although prothrombin time (usually expressed as
      International normalized ratio [INR]) is the most common warfarin response
      marker, clotting factors (namely factors II and X) are also indicated as
      alternative anticoagulant effect markers. In this paper, we examine the
      relationship between these warfarin response markers using information obtained
      from eighty 80 patients undergoing long-term warfarin therapy. Within the usual
      INR therapeutic range (2.0-3.5), a moderate inverse correlation between INR and
      both clotting factors II and X was observed. However, for INR values above 3.5, a
      non-proportional relationship were found between INR and both response markers.
      Therefore, it can be concluded that below critical clotting factor concentrations
      (20.6% and 15.6% of factors II and X activity, respectively), time required for
      clot formation becomes non-proportional and haemostasis will be jeopardised.

PMID- 20045628
TI  - The impact of isolated tibial disease on outcomes in the critical limb ischemic
      population.
AB  - BACKGROUND: Most patients with critical limb ischemia (CLI) have multilevel
      infrainguinal peripheral arterial disease (M-PAD). One-third of CLI patients will
      have isolated tibial disease (ITD). The treatments for multilevel disease or ITD
      differ depending on whether open or endovascular procedures are used, but we
      questioned whether outcomes from these procedures differ. We evaluated outcomes
      of CLI patients after open and/or endovascular revascularization for CLI and
      assessed the impact of disease distribution. METHODS: Four hundred forty-six CLI
      patients (Rutherford 4-6) who underwent revascularization from 2001 to 2005 were
      evaluated arteriographically and followed after revascularization with
      noninvasive testing. Based on arteriographic data, all patients with ITD
      (occlusions in one or more tibial arteries) were compared with patients with
      occlusive femoropopliteal disease with or without concomitant tibial occlusions
      (M-PAD). Patients with disease solely above the inguinal ligament were excluded.
      Clinical data (survival, amputation-free survival, primary patency, secondary
      patency, limb salvage, maintenance of ambulation, and maintenance of living
      status) were acquired from a prospective vascular database, allowing the
      comparison of revascularization outcomes according to disease distribution.
      RESULTS: In this study, 36% of patients had ITD and 64% presented with M-PAD. The
      severity of ischemia at presentation was rest pain (28.5%), ulceration (42.3%),
      and gangrene (29.1%). In this study, 92% presented exclusively with infrainguinal
      disease, and 8% presented with both suprainguinal and infrainguinal disease. Risk
      factors included diabetes mellitus (61.2%), smoking (61.0%), coronary artery
      disease (57.9%), hypertension (84.3%), hyperlipidemia (40.4%), obesity (15.5%),
      and chronic obstructive pulmonary disease (19.3%). In comparing the ITD and M-PAD
      groups, there was no difference in primary patency at 2 years. All other outcomes
      were statistically different out to 3 years including survival (50.4% vs. 62.6%;
      p=0.0026, hazard ratio [HR] 0.669); amputation-free survival (35.1% vs. 50.2%;
      p=0.0062; HR 0.595); limb salvage (65.2% vs. 74.4%; p=0.0062; HR 0.595);
      maintenance of ambulation (68.9% vs. 76.9%; p=0.0352; HR 0.644); maintenance of
      living status (79.0% vs. 84.8%; p=0.0403; HR 0.599); and secondary patency (66.8%
      vs. 74.8%; p=0.0309; HR 0.665). Multivariate analyses reveal that ITD is not an
      independent predictor of outcome after controlling for confounding factors, of
      which tissue loss and end-stage renal disease correlate most consistently with
      poor clinical outcomes. CONCLUSION: After revascularization for CLI, ITD carries
      a worse prognosis (amputation-free survival, limb salvage, survival, maintenance
      of ambulation, and independent living status) compared with patients with M-PAD,
      despite the "greater" disease burden in M-PAD patients. ITD patients are more
      likely to have confounding factors such as diabetes mellitus, renal disease, and
      worse ischemia at presentation than those with M-PAD. The recognition of ITD may
      be helpful in identifying high-risk patients but is not an independent risk
      factor for poor outcomes.

PMID- 20045629
TI  - Disappearing flapping plaque in the internal carotid artery.
AB  - Mobile atheromatous plaque at the origin of the internal carotid artery (ICA) is
      a rare finding at the carotid ultrasound examination. Acute thrombosis is
      unusually seen. Either may be secondary to plaque hemmorhage, plaque ulceration,
      carotid dissection, or proximal embolus. We report an 89-year-old male suffering
      from an acute neurologic event who on ultrasound had a flapping heterogeneous
      atheromatous plaque at the right ICA origin. This mobile atheromatous plaque is
      distinguished from acute thrombus by its echogenicity, narrow pedicle of
      attachment, and absence of underlying intima. Subsequent computed tomography
      angiography and repeat ultrasound within 24 hr demonstrated the disappearance of
      this plaque. Only three small intimal flaps remained. In the intervening period,
      the patient's symptoms significantly worsened. While conservative management of
      thrombus with intravenous thrombolysis has been shown in some settings to be
      appropriate, the diagnosis and management of mobile atheroma are unclear. This
      case suggests that differentiation between atheroma and thrombus may be valuable
      in determining management strategies.

PMID- 20045630
TI  - Relationships amongst age, language and related skills in adults with Down
      syndrome.
AB  - Studies into the effects of ageing on language in adults with Down syndrome (DS)
      have tended to rely on measures that lack sensitivity to change because they fail
      to explore across linguistic domains or rely on proxy reports. The study aim was
      to use measures of receptive and expressive language from studies of younger
      individuals with DS in exploring relationships across linguistic and associated
      skills, and age in young to older adults. Fifty-five adults (aged 19-58 years),
      10 with a diagnosis of or signs of early stage Alzheimer's Disease (AD), provided
      data on measures of functioning associated with AD, non-verbal cognition,
      receptive language (which provided a measure of mental age), receptive and
      expressive language, and short term auditory and visual memory. The first order
      correlation between the measure of AD and CA was significant; but not when the 10
      participants with AD were removed from the analysis. Significant negative
      correlations were obtained between CA and all other measures; small to large
      significant positive correlations were found amongst the other measures. Partial
      correlations were conducted to remove the potential effects of AD and IQ (the
      latter measured by a test of non-verbal cognition). Remaining significant
      correlations were between auditory short term memory and all other included
      measures, expressive language and all other included measures, and CA and
      auditory short term memory and expressive language. The results indicate that
      deterioration with age in this cross-sectional study was accounted for largely by
      the presence of AD. The exceptions were for auditory short term memory and
      expressive language. The findings may reflect an underlying deficit in auditory
      short term memory for adults with DS, as has been found in previous research of
      children and adolescents. The implications are discussed in terms of the
      importance of including comprehensive measures of receptive and expressive
      language and the need to account for the presence of AD in studies of cognitive
      decline associated with ageing in DS.

PMID- 20045631
TI  - Understanding neurodynamical systems via Fuzzy Symbolic Dynamics.
AB  - Neurodynamical systems are characterized by a large number of signal streams,
      measuring activity of individual neurons, local field potentials, aggregated
      electrical (EEG) or magnetic potentials (MEG), oxygen use (fMRI) or activity of
      simulated neurons. Various basis set decomposition techniques are used to analyze
      such signals, trying to discover components that carry meaningful information,
      but these techniques tell us little about the global activity of the whole
      system. A novel technique called Fuzzy Symbolic Dynamics (FSD) is introduced to
      help in understanding of the multidimensional dynamical system's behavior. It is
      based on a fuzzy partitioning of the signal space that defines a non-linear
      mapping of the system's trajectory to the low-dimensional space of membership
      function activations. This allows for visualization of the trajectory showing
      various aspects of observed signals that may be difficult to discover looking at
      individual components, or to notice otherwise. FSD mapping can be applied to raw
      signals, transformed signals (for example, ICA components), or to signals defined
      in the time-frequency domain. To illustrate the method two FSD visualizations are
      presented: a model system with artificial radial oscillatory sources, and the
      output layer (50 neurons) of Respiratory Rhythm Generator (RRG) composed of 300
      spiking neurons.

PMID- 20045632
TI  - Dissecting the ribosomal inhibition mechanism of a new ketolide carrying an alkyl
      aryl group at C-13 of its lactone ring.
AB  - Ketolides are effective not only against macrolide-sensitive bacteria but also
      against some macrolide-resistant strains. Here we present data regarding a new
      ketolide with an alkyl-aryl side chain at C-13 of its lactone ring. It behaves as
      a strong inhibitor of protein synthesis in a model coupled
      transcription/translation system, although it does not affect the accuracy of
      translation. In addition, detailed kinetic analysis shows that it slowly forms a
      very tight, slowly reversible complex with prokaryotic ribosomes, a property that
      could be correlated with its superior activity compared with erythromycin against
      Escherichia coli both in vivo and in vitro.

PMID- 20045633
TI  - Saving transverse magnetization.
AB  - A magnetization storage sequence, ALT-1 (alternating longitudinal and transverse
      components), is reported. The ALT-1 sequence is a hybrid of two types of storage
      sequences, the Carr-Purcell type and store-and-restore sequences. During
      incremental storage periods within the ALT-1 sequence, essentially half of the
      initially transverse magnetization is stored along the z-axis and the other half
      is prolonged by an echo-generating pulse. The portions of initial magnetization
      that are stored as longitudinal components or transverse components are
      alternated by a pi/2 pulse during the cycle. Both transverse components of the
      initial magnetization are treated the same in the ALT-1 sequence and
      orientational (phase) information of the initial magnetization is kept during the
      storage period. The ALT-1 sequence can preserve magnetization more effectively
      than a published class of modified Carr-Purcell type sequences, because
      essentially half of the magnetization during incremental storage periods is not
      subjected to relaxation from T2 effects.

PMID- 20045634
TI  - Experimental application of electrolysis in the treatment of liver and pancreatic
      tumours: principles, preclinical and clinical observations and future
      perspectives.
AB  - BACKGROUND: Electrolytic ablation (EA) is a treatment that destroys tissues
      through electrochemical changes in the local microenvironment. This review
      examined studies using EA for the treatment of liver and pancreatic tumours, in
      order to define the characteristics that could endow the technique with specific
      advantages compared with other ablative modalities. METHODS: Literature search of
      all studies focusing on liver and pancreas EA. RESULTS: A specific advantage of
      EA is its safety even when conducted close to major vessels, while a disadvantage
      is the longer ablation times compared to more frequently employed techniques.
      Bimodal electric tissue ablation modality combines radiofrequency with EA and
      produced significant larger ablation zones compared to EA or radiofrequency
      alone, reducing the time required for ablation. Pancreatic EA has been
      investigated in experimental studies that confirmed similar advantages to those
      found with liver ablation, but has never been evaluated on patients. Furthermore,
      few clinical studies examined the results of liver EA in the short-term but there
      is no appropriate follow-up to confirm any survival advantage. CONCLUSIONS: EA is
      a safe technique with the potential to treat lesions close to major vessels.
      Specific clinical studies are required to confirm the technique's safety and
      eventually demonstrate a survival advantage.

PMID- 20045636
TI  - Enhanced efficiency of biological excess sludge hydrolysis under anaerobic
      digestion by additional enzymes.
AB  - In this investigation, the effects of commercial enzyme preparation containing
      alpha amylase and neutral protease on hydrolysis of excess sludge and the kinetic
      analysis of hydrolysis process were evaluated. The results indicated that amylase
      treatment displayed higher hydrolysis efficiency than that of protease. VSS
      reduction greatly increased to 39.70% for protease and 54.24% for amylase at the
      enzyme dosage of 6% (w/w), respectively. The hydrolysis rate of sludge improved
      with temperature increasing from 40 to 50 degrees Celsius, which could be well
      described by the amended Arrhenius equation. Mixed-enzyme had great impact on
      sludge solubilisation than single enzyme. The mixture of two enzymes
      (protease:amylase=1:3) resulted in optimum hydrolysis efficiency, the efficiency
      of solids hydrolysis increased from 10% (control test) to 68.43% at the
      temperature of 50 degrees Celsius. Correspondingly, the concentration of reducing
      sugar and NH(4)(+)-N improved about 377% and 201%, respectively. According to the
      kinetic analysis of enzymatic hydrolysis process, VSS solubilisation process
      within prior 4 h followed first-order kinetics. Compared with control test, the
      hydrolysis rate improved significantly at 50 degrees Celsius when either single
      enzyme or mixed-enzyme was added.

PMID- 20045635
TI  - Combined effect of water and KOH on rapeseed oil methanolysis.
AB  - This paper deals with the effect of water and catalyst (KOH) amount on the
      quantity and quality of transesterification products of rapeseed oil by methanol,
      the methyl ester phase (i.e. yield, conversion), and the side-product, the
      glycerol phase (i.e. density, viscosity, the mass fraction of glycerol, esters,
      soaps). The dependencies were described by statistical models. The
      transesterification was carried out at constant reaction conditions (90 min
      reaction time, 400 rpm, 60 degrees Celsius). Twelve experiments with the
      independent factors, amount of potassium hydroxide (0.65-0.9 mg per gram of oil)
      and total amount of water (0.24-1.42 mg per gram of oil) naturally present in the
      reaction components or formed by the neutralisation reaction of free fatty acids
      and of added water. The data were analyzed by linear regression with respect to
      regression triplet (complex critical analysis of the model, data and regression
      method). The analysis resulted in a set of linear and/or quadratic models
      consisting of statistically proven terms at a statistical significance level of
      0.05 and demonstrated that ester in the glycerol phase increases with increasing
      amount of soaps.

PMID- 20045637
TI  - Tuber melanosporum fermentation medium optimization by Plackett-Burman design
      coupled with Draper-Lin small composite design and desirability function.
AB  - A novel method using Plackett-Burman design (PBD) coupled with Draper-Lin small
      composite design (SCD) and desirability function (DF) was developed to optimize
      Tuber melanosporum fermentation medium. Firstly, sucrose, yeast extract, peptone
      and Mg(2+) were identified to be key medium components by PBD. Secondly, in order
      to evaluate the relationships between responses and the identified key
      components, mathematical models were developed by SCD. Finally, by using DF, the
      responses were optimized simultaneously and the optimal concentration was located
      to be 73 g/L sucrose, 11 g/L yeast extract, 8 g/L peptone, and 46 mM Mg(2+).
      Under the identified optimal conditions, the maximal biomass, the production of
      extracellular (EPS) and intracellular (IPS) polysaccharides was 25.10 + or - 0.12
      g/L, 3.88 + or - 0.23 g/L and 2.87 + or - 0.32 g/L, respectively, which agreed
      with the predicted values well. Compared with the basic medium, the biomass, the
      production of EPS and IPS was enhanced by 54.4%, 71.7% and 124.2%, respectively.

PMID- 20045638
TI  - Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent
      FBPase inhibitors.
AB  - With the goal of improving metabolic stability and further enhancing FBPase
      inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was
      designed and synthesized with the aid of structure-based drug design. Extensive
      SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human
      FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due
      to the hydrophobic interaction arising from better shape complementarity and to
      the hydrogen bonding network involving the side chain on the tricyclic scaffold.

PMID- 20045639
TI  - Design, synthesis and biological evaluation of simplified analogues of the RNA
      polymerase inhibitor etnangien.
AB  - Novel simplified analogues of the potent RNA polymerase inhibitor etnangien were
      obtained by total synthesis and evaluated for antibacterial activity against Gram
      positive bacteria and one Gram-negative bacterium.

PMID- 20045640
TI  - Synthesis, antimalarial and antitubercular activity of acetylenic chalcones.
AB  - A series of acetylenic chalcones were evaluated for antimalarial and
      antitubercular activity. The antimalarial data for this series suggests that
      growth inhibition of the W2 strain of Plasmodium falciparum can be imparted by
      the introduction of a methoxy group ortho to the acetylenic group. Most compounds
      were more active against non-replicating than replicating cultures of
      Mycobacterium tuberculosis H(37)Rv, an unusual pattern with respect to existing
      anti-TB agents.

PMID- 20045641
TI  - 9-Aminomethyl-9,10-dihydroanthracene (AMDA) analogs as structural probes for
      steric tolerance in 5-HT2A and H1 receptor binding sites.
AB  - Synthesis, radioligand binding and molecular modeling studies of several 9
      aminomethyl-9,10-dihydroanthracene (AMDA) analogs were carried out to determine
      the extent of the steric tolerance associated with expansion of the tricyclic
      ring system and amine substitution at 5-HT(2A) and H(1) receptors. A mixture of
      (7,12-dihydrotetraphene-12-yl)methanamine and (6,11-dihydrotetracene-11
      yl)methanamine in a 75-25% ratio was found to have an apparent K(i) of 10nM at
      the 5-HT(2A) receptor. A substantial binding affinity for (7,12-dihydrotetraphene
      3-methoxy-12-yl)methanamine at the 5-HT(2A) receptor (K(i)=21 nM) was also
      observed. Interestingly, this compound was found to have 100-fold selectivity for
      5-HT(2A) over the H(1) receptor (K(i)=2500 nM). N-Phenylalkyl-AMDA derivatives,
      in which the length of the alkyl chain varied from methylene to n-butylene, were
      found to have only weak affinity for both 5-HT(2A) and H(1) receptors (K(i)=223
      to 964 nM). Our results show that large rigid annulated AMDA analogs can be
      sterically accommodated within the proposed 5-HT(2A) binding site.

PMID- 20045642
TI  - In silico discovery of 2-amino-4-(2,4-dihydroxyphenyl)thiazoles as novel
      inhibitors of DNA gyrase B.
AB  - Cyclothialidines are a class of bacterial DNA gyrase B (GyrB) subunit inhibitors,
      targeting its ATP-binding site. Starting from the available structural
      information on cyclothialidine GR122222X (2), an in silico virtual screening
      campaign was designed combining molecular docking calculations with three
      dimensional structure-based pharmacophore information. A novel class of 2-amino-4
      (2,4-dihydroxyphenyl)thiazole based inhibitors (5-9) with low micromolar
      antigyrase activity was discovered.

PMID- 20045643
TI  - Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic
      acid conjugate.
AB  - Acetylated (Ac) dendrimer poly(amido)-amine (PAMAM) generation 5 (G5) reacted
      with folic acid (FA), followed by reacting with 2-(p-isothiocyanatobenzyl)-6
      methyl-diethylenetria minepentaacetic acid (1B4M DTPA) to form the conjugate of
      Ac-G5-FA-1B4M DTPA which was further radiolabeled with (99m)Tc. The radiochemical
      yield is up to 98.9% with excellent in vitro/in vivo stability, rapid blood
      clearance and certain tumor accumulation which was further confirmed by micro
      SPECT imaging study.

PMID- 20045644
TI  - Polar 3-alkylidene-5-pivaloyloxymethyl-5'-hydroxymethyl-gamma-lactones as protein
      kinase C ligands and antitumor agents.
AB  - A series of DAG-lactones with polar 3-alkylidene substituents have been
      investigated as PKC-alpha ligands and antitumor agents. Extensive analysis of
      structure-activity relationships for the 3-alkylidene chain revealed that polar
      groups such as ether, hydroxyl, aldehyde, ester, acyloxy, and amido were
      tolerated with similar binding affinities and reduced lipophilicities compared to
      the corresponding unsubstituted alkylidene chain. Among the derivatives,
      compounds 5, 6 and 8 with an ether type of side chain showed high binding
      affinities in range of K(i)= 3-5 nM and excellent antitumor profiles,
      particularly against the colo205 colon cancer and the K562 leukemia cell lines.

PMID- 20045645
TI  - Discovery and optimization of RO-85, a novel drug-like, potent, and selective
      P2X3 receptor antagonist.
AB  - Despite the extensive literature describing the role of the ATP-gated P2X(3)
      receptors in a variety of physiological processes the potential of antagonists as
      therapeutic agents has been limited by the lack of drug-like selective molecules.
      In this paper we report the discovery and optimization of RO-85, a novel drug
      like, potent and selective P2X(3) antagonist. High-throughput screening of the
      Roche compound collection identified a small hit series of heterocyclic amides
      from a large parallel synthesis library. Rapid optimization, facilitated by high
      throughput synthesis, focusing on increasing potency and improving drug-likeness
      resulted in the discovery of RO-85.

PMID- 20045646
TI  - New iodinated quinoline-2-carboxamides for SPECT imaging of the translocator
      protein.
AB  - With the aim of developing new SPECT imaging agents for the translocator protein
      (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared
      and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4
      phenylquinoline-2-carboxamide was found to have excellent affinity (K(i) 12.0
      nM), comparable to that of the widely used TSPO imaging agent PK11195.

PMID- 20045647
TI  - Synthesis and optimization of thiadiazole derivatives as a novel class of
      substrate competitive c-Jun N-terminal kinase inhibitors.
AB  - A series of thiadiazole derivatives has been designed as potential allosteric,
      substrate competitive inhibitors of the protein kinase JNK. We report on the
      synthesis, characterization and evaluation of a series of compounds that resulted
      in the identification of potent and selective JNK inhibitors targeting its JIP-1
      docking site.

PMID- 20045648
TI  - Di-substituted pyridinyl aminohydantoins as potent and highly selective human
      beta-secretase (BACE1) inhibitors.
AB  - The identification of highly selective small molecule di-substituted pyridinyl
      aminohydantoins as beta-secretase inhibitors is reported. The more potent and
      selective analogs demonstrate low nanomolar potency for the BACE1 enzyme as
      measured in a FRET assay, and exhibit comparable activity in a cell-based (ELISA)
      assay. In addition, these pyridine-aminohydantoins are highly selectivity (>500x)
      against the other structurally related aspartyl proteases BACE2, cathepsin D,
      pepsin and renin. Our design strategy followed a traditional SAR approach and was
      supported by molecular modeling studies based on the previously reported
      aminohydantoin 3a. We have taken advantage of the amino acid difference between
      the BACE1 and BACE2 at the S2' pocket (BACE1 Pro(70) changed to BACE2 Lys(86)) to
      build ligands with >500-fold selectivity against BACE2. The addition of large
      substituents on the targeted ligand at the vicinity of this aberration has
      generated a steric conflict between the ligand and these two proteins, thus
      impacting the ligand's affinity and selectivity. These ligands have also shown an
      exceptional selectivity against cathepsin D (>5000-fold) as well as the other
      aspartyl proteases mentioned. One of the more potent compounds (S)-39 displayed
      an IC(50) value for BACE1 of 10nM, and exhibited cellular activity with an EC(50)
      value of 130nM in the ELISA assay.

PMID- 20045649
TI  - Synthesis and structural and pharmacological properties of cyclopropane-based
      conformationally restricted analogs of 4-methylhistamine as histamine H3/H4
      receptor ligands.
AB  - On the basis of the previous results on a histamine H(4) receptor agonist 4
      methylhistamine and a cyclopropane-based conformationally restricted analog CEIC
      (3) with potent H(3)/H(4) receptor antagonistic effect, 4-methylhistamine analogs
      4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity
      (K(i)=38.7 nM) for the H(3) receptor, which was more potent than a well-known
      H(3) antagonist thioperamide. Stable tautomer and conformation of 3 and 4, which
      can affect the pharmacological activity, were analyzed by ab initio calculations.

PMID- 20045650
TI  - A new series of flavones, thioflavones, and flavanones as selective monoamine
      oxidase-B inhibitors.
AB  - A new series of synthetic flavones, thioflavones, and flavanones has been
      synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms
      (MAO-A and -B). The most active series is the flavanone one with higher selective
      inhibitory activity against MAO-B. Some of these flavanones (mainly the most
      effective) have been separated and tested as single enantiomers. In order to
      investigate the MAOs recognition of the most active and selective compounds, a
      molecular modeling study has been performed using available Protein Data Bank
      (PDB) structures as receptor models for docking experiments.

PMID- 20045651
TI  - Structure and in vitro antitumor activity evaluation of brominated diterpenes
      from the red alga Sphaerococcus coronopifolius.
AB  - A novel bromoditerpene methyl ketone (1), two new bromoditerpene alcohols
      featuring a neodolastane (2), and a bromocorodienol skeleton (3), along with 13
      previously reported metabolites (4-16) were isolated from the organic extract of
      Sphaerococcus coronopifolius collected from the rocky coasts of Corfu island in
      the Ionian Sea. The structures of the new natural products, as well as their
      relative stereochemistry, were elaborated on the basis of extensive spectral
      analysis, including 2D NMR experiments. The absolute stereochemistry of
      metabolite 3 was determined using the modified Mosher's method. The isolated
      metabolites were evaluated for their antitumoral activity against four human
      apoptosis-resistant (U373, A549, SKMEL-28, OE21) and two human apoptosis
      sensitive (PC-3, LoVo) cancer cell lines with IC(50) in vitro growth inhibitory
      concentrations in the range 3-100 microM.

PMID- 20045652
TI  - Square pyramidal copper(II) complexes with forth generation fluoroquinolone and
      neutral bidentate ligand: structure, antibacterial, SOD mimic and DNA-interaction
      studies.
AB  - Coordination of neutral bidentate ligand to copper ion in combination with
      gatifloxacin have been focused in this article. The effect of complexation
      reflects antibacterial activity, DNA interaction and SOD mimic activity of
      individual greatly. The geometry at the central metal ion provides a site for
      binding of superoxide anion responsible for better SOD mimic behaviour.

PMID- 20045653
TI  - Th17/Th1 phenotype in demyelinating disease.
AB  - BACKGROUND: Th17 cells are thought to contribute to the immunopathology of
      allergic and autoimmune conditions. Their role in multiple sclerosis (MS)
      pathology remains to be fully elucidated. OBJECTIVE: To assess peripheral blood
      Th17 responses in patients with MS compared to controls. METHODS: We isolated
      peripheral blood mononuclear cells from 41 MS patients and 23 healthy controls,
      which were then stimulated using phorbol ester and ionomycin, labelled for CD3,
      CD8, CD154, IL-17 and IFN-gamma and analysed using flow cytometry. RESULTS:
      Minimal IL-17 was detectable in unstimulated cells. Following stimulation with
      phorbol ester and ionomycin, PBMCs taken from MS patients in relapse developed a
      more inflammatory profile than those taken from controls or non-relapse patients,
      with greater expression of CD154, IL-17 and dual expression of IL-17/IFN-gamma.
      CONCLUSION: We suggest a greater tendency to Th17 and Th1/Th17 response to non
      specific stimulation in MS patients in relapse compared to controls and non
      relapse patients.

PMID- 20045654
TI  - Polymorphisms of signal transducers and activators of transcription 1 and 4
      (STAT1 and STAT4) contribute to progression of childhood IgA nephropathy.
AB  - BACKGROUND: Several experimental studies have suggested that signal transducers
      and activators of transcription 1 and 4 (STAT1 and STAT4) play important roles in
      the regulation of mesangial proliferation and renal fibrosis, and in the
      development of inflammation in several types of glomerulonephritis. METHODS: The
      present study was conducted to investigate the association between single
      nucleotide polymorphisms (SNPs) of the STAT1 and STAT4 genes and childhood IgA
      nephropathy (IgAN). RESULTS: Genotyping of 170 childhood IgAN patients and 442
      controls showed no significant differences in allele frequency. However, patient
      subgroup analysis revealed that development of proteinuria ( and >4mg/m(2)/h) was
      associated with STAT1 rs10199181 (dominant model, P=0.035) and high serum level
      of IgA with STAT1 rs6718902 (dominant model, P=0.035) and STAT1 rs2280232
      (codominant model, P=0.014; dominant model, P=0.022). Furthermore, some SNP
      frequencies were significantly different between patients with pathologically
      mild and advanced disease; STAT1 rs6718902 (overdominant model, P=0.030), STAT1
      rs10199181 (codominant model, P=0.023; dominant model, P=0.012; overdominant
      model, P=0.018), and STAT4 rs7561832 (dominant model, P=0.026; overdominant
      model, P=0.029). CONCLUSIONS: Our results suggest that polymorphisms of STAT1 and
      STAT4 are associated with increased susceptibility, pathological advancement, and
      development of proteinuria in childhood IgAN.

PMID- 20045655
TI  - Detection of neck recanalization with follow-up contrast-enhanced MR angiography
      after renal artery aneurysm coil embolization.

PMID- 20045656
TI  - Intentional binding and higher order agency experience.
AB  - Recent research has shown that human instrumental action is associated with
      systematic changes in time perception: The interval between a voluntary action
      and an outcome is perceived as shorter than the interval between a physically
      similar involuntary movement and an outcome. The study by, Ebert and Wegner
      (2010) suggests that this change in time perception is related to higher order
      agency experience. Notwithstanding certain issues arising from their study, which
      are discussed, we believe it offers validation of binding as a measure of sense
      of agency.

PMID- 20045657
TI  - Accuracy, determinants, and consequences of body weight self-perception in type 2
      diabetes: the Fremantle Diabetes Study.
AB  - OBJECTIVE: To assess the accuracy, determinants, and consequences of body weight
      self-perception in type 2 diabetes. METHODS: We studied 1272 community-based
      patients and a 518-patient overweight/obese subset who returned for >=4 annual
      reviews. Multiple logistic regression was used to identify baseline predictors of
      correct weight self-perception and to determine whether correct weight self
      perception predicted future weight loss. Overweight and obesity were defined as
      body mass indices of 25.0-29.9 and >=30.0 kg/m(2), respectively. RESULTS: Of the
      patients who were overweight (40.0%) or obese (41.8%) at baseline, 52.8% and
      83.7%, respectively, correctly self-identified their weight category.
      Overweight/obese participants who self-identified correctly were more likely to
      have been informed they were overweight (P<.001), predominantly by their general
      practitioner (80.1%). Overweight participants had less self-awareness if they
      were not abdominally obese, did not speak English fluently, were male, or had a
      low income. Obese participants were more likely to consider themselves overweight
      if they had better diabetes knowledge and higher educational attainment. Correct
      weight self-perception did not influence subsequent weight loss. CONCLUSIONS:
      Health care professionals can facilitate body weight self-awareness in type 2
      diabetes. Education programmes should recognise the impact of gender and socio
      demographic variables on accurate weight self-perception.

PMID- 20045658
TI  - L-band Overhauser dynamic nuclear polarization.
AB  - We present the development of an Overhauser dynamic nuclear polarization (DNP)
      instrument at 0.04 T using 1.1 GHz (L-band) electron spin resonance frequencies
      (ESR) and 1.7 MHz (1)H nuclear magnetic resonance frequencies. Using this home
      built DNP system, the electron-nucleus coupling factor of 4-oxo-TEMPO dissolved
      in water was determined as 0.39+/-0.06 at 0.04 T. The higher coupling factor
      obtained at this field compared to higher magnetic fields, such as 0.35 T,
      directly translates to higher enhancement of the NMR signal and opens up a wider
      time scale window for observing water dynamics interacting with macromolecular
      systems, including proteins, polymers or lipid vesicles. The higher enhancements
      obtained will facilitate the observation of water dynamics at correlation times
      up to 10 ns, that corresponds to more than one order of magnitude slower dynamics
      than accessible at 0.35 T using X-band ESR frequencies.

PMID- 20045660
TI  - Benchmarking NMR experiments: a relational database of protein pulse sequences.
AB  - Systematic benchmarking of multi-dimensional protein NMR experiments is a
      critical prerequisite for optimal allocation of NMR resources for structural
      analysis of challenging proteins, e.g. large proteins with limited solubility or
      proteins prone to aggregation. We propose a set of benchmarking parameters for
      essential protein NMR experiments organized into a lightweight (single XML file)
      relational database (RDB), which includes all the necessary auxiliaries
      (waveforms, decoupling sequences, calibration tables, setup algorithms and an RDB
      management system). The database is interfaced to the Spinach library
      (http://spindynamics.org), which enables accurate simulation and benchmarking of
      NMR experiments on large spin systems. A key feature is the ability to use a
      single user-specified spin system to simulate the majority of deposited solution
      state NMR experiments, thus providing the (hitherto unavailable) unified
      framework for pulse sequence evaluation. This development enables predicting
      relative sensitivity of deposited implementations of NMR experiments, thus
      providing a basis for comparison, optimization and, eventually, automation of NMR
      analysis. The benchmarking is demonstrated with two proteins, of 170 amino acids
      I domain of alphaXbeta2 Integrin and 440 amino acids NS3 helicase.

PMID- 20045659
TI  - ESR micro-imaging of LiNc-BuO crystals in PDMS: spatial and spectral grain
      distribution.
AB  - Microcrystals of lithium octa-n-butoxynaphthalocyanine (LiNc-BuO) in a bio
      compatible and oxygen-permeable polymer matrix of poly-dimethyl-siloxane (PDMS)
      can be used for repetitive non-invasive imaging of oxygen in live specimens by
      means of mm-scale electron spin resonance (ESR) imaging. This probe denoted as
      "oxychip" was characterized by high-resolution mum-scale ESR microcopy to reveal
      the fine details of its spatial and spectral properties. The ESR micro-images of
      a typical oxychip device showed that while the spatial distribution of the
      microcrystals in the polymer is fairly homogenous (as revealed by optical
      microscopy), the ESR signal originates only from a very few dominant crystals.
      Furthermore, spectral-spatial analysis in a microcrystal and a sub-microcrystal
      spatial resolution reveals that each crystal has a slightly different g-factor
      and also exhibits variations in linewidth, possibly due to the slightly different
      individual crystallization process.

PMID- 20045661
TI  - A sonochemical method for the preparation of cadmium sulfide and cadmium selenide
      nanoparticles in aqueous solutions.
AB  - Sonochemistry is a branch of chemistry where sound energy in the form of
      ultrasound is used to influence the course of reactions. A short-term, local
      increase in temperature occurs when the solutions and suspensions are irradiated
      by ultrasound. This happens because the substance absorbs the ultrasound waves.
      The purpose of this research was the synthesis of CdS and CdSe nanoparticles. We
      used cadmium sulfate hydrate (CdSO(4).8/3H(2)O), elemental S and Se. Aqueous
      solutions of NaOH, Na(2)SO(3) and EDTA were used as the solvents. During the
      syntheses, we used a direct immersion ultrasound probe by vibracell. The device
      operates with a constant frequency of 20 kHz, with the possibility to change the
      amplitude and with it the input of energy to the time unit. The products were
      characterized by X-ray powder diffraction (XRD), thermal analyses (TGA, SDTA) and
      TEM analyses.

PMID- 20045662
TI  - Investigation on interaction of prulifloxacin with pepsin: a spectroscopic
      analysis.
AB  - The interaction between prulifloxacin, a kind of new oral taking antibiotic and
      pepsin, a kind of enzyme in the stomach has been investigated in vitro under a
      simulated physiological condition by different spectroscopic methods. The
      intrinsic fluorescence of pepsin was strongly quenched by prulifloxacin. This
      effect was rationalized in terms of a static quenching procedure. The binding
      parameters have been evaluated by fluorescence quenching methods. The negative
      value of DeltaG(0) reveals that the binding process is a spontaneous process. The
      binding distance R between donor (pepsin) and acceptor (prulifloxacin) was
      obtained according to the Forster's resonance energy transfer theory and found to
      be 0.95 nm. The results obtained herein will be of biological significance in
      pharmacology and clinical medicine.

PMID- 20045663
TI  - The relationship between mental retardation and developmental delays in children
      and the levels of arsenic, mercury and lead in soil samples taken near their
      mother's residence during pregnancy.
AB  - This study was designed to evaluate the association between lead, mercury, and
      arsenic in the soil near maternal residences during pregnancy and mental
      retardation or developmental disability (MR/DD) in children. The study was
      conducted using 6,048 mothers who did not move throughout their pregnancies and
      lived within six strips of land in South Carolina and were insured by Medicaid
      between January 1, 1997 and December 31, 2002. The mother child pairs were then
      followed until June 1, 2008, through their Medicaid reimbursement files, to
      identify children diagnosed with MR/DD. The soil was sampled for mercury (Hg),
      lead (Pb), and As based on a uniform grid, and the soil concentrations were
      Kriged to estimate chemical concentration at individual locations. We identified
      a significant relationship between MR/DD and As, and the form of the relationship
      was nonlinear, after controlling for other known risk factors.

PMID- 20045664
TI  - Constructed wetlands--Are they safe in reducing protozoan parasites?
AB  - Constructed wetlands have been promoted in recent literature for use in rural
      communities in developed as well as in developing countries as an appropriate
      technology to be handled with low operational maintenance costs. Within a joint
      project supported by BMBF (Project No O2WA0107 and No 02WA0108) research was done
      concerning the sanitation effect of constructed wetlands on wastewater effluents.
      This article will focus on the detection and the removal of cysts of
      Cryptosporidium parvum and Giarda lamblia, those being the most frequently
      identified pathogenic protozoan parasites worldwide with increasing medical and
      economical consequences. Two plants, one installed in 2000 as a pilot plant at
      Langenreichenbach near Leipzig (Saxony, Germany), the other one in routine
      operation since 1993 in a training center at the town of Belzig (Brandenburg,
      Germany) were tested for three years. Detection methods from the US EPA (ICR
      Protozoan Method for Detecting Giardia Cysts and Cryptosporidium Oocysts in Water
      by a Fluorescent Antibody Procedure (EPA/814-B-95-003;US EPA 1995) were employed
      in order to assess protozoal and bacterial reduction in the wastewater passing
      through different combinations of filter beds and fillings. Removal of cysts of
      Cryptosporidium and Giardia spp. turned out to be a 2 log reduction in all
      plants. The most effective structural element was a two-stage combination of
      filter beds leading to the highest removal efficiency both for the protozoan and
      the bacterial indicator organisms. Also, washed sand (0-2mm grain size) in the
      filter bed proved to be most effective filter material; the planted reed
      (phragmites spp.) or willow (salix spp.), however, turned out to be of minor
      importance for the filtering activity.

PMID- 20045665
TI  - Tuberculosis research: going forward with a powerful "translational systems
      biology" approach.
AB  - Due to the complexity of the immune response to a Mycobacterium tuberculosis
      infection, identifying new, effective therapies and vaccines to combat it has
      been a problematic issue. Although many advances have been made in understanding
      particular mechanisms involved, they have, to date, proved insufficient to
      provide real breakthroughs in this area of tuberculosis research. The term
      "Translational Systems Biology" has been formally proposed to describe the use of
      experimental findings combined with mathematical modeling and/or engineering
      principles to understand complex biological processes in an integrative fashion
      for the purpose of enhancing clinical practice. This opinion piece discusses the
      importance of using a Translational Systems Biology approach for tuberculosis
      research as a means by which to go forward with the potential for significant
      breakthroughs to occur.

PMID- 20045666
TI  - When do psychogenic nonepileptic seizures occur on a video/EEG telemetry unit?
AB  - To maximize the efficiency of diagnostic video/EEG telemetry, we retrospectively
      studied the occurrence of clinical events during admission in 254 patients. One
      hundred fifty-nine patients had psychogenic nonepileptic seizures (PNES) and 95
      had epileptic seizures (ES). Twenty-five with PNES and none with ES had an event
      before or during electrode placement (P<0.0001). In the remaining 229, the
      initial event occurred within 48 hours of electrode placement in 98.5% patients
      with PNES and 100.0% of patients with ES. Time to occurrence of initial event did
      not differ between groups (P=0.69). 17.1% patients with PNES and 51.6% with ES
      had events between 12 AM and 6 AM (P=0.001). In conclusion, during diagnostic
      video/EEG telemetry, most patients who experience PNES or ES have diagnostic,
      typical events within 2 days. Although time to initial event after electrode
      placement does not differ between diagnoses, events prior to or during placement
      are most likely PNES and events at night are most likely ES.

PMID- 20045667
TI  - Characteristics of psychogenic nonepileptic events among veterans with
      posttraumatic stress disorder: an association of semiology with the nature of
      trauma.
AB  - Various psychiatric disorders can contribute to psychogenic nonepileptic events
      (PNEEs), including posttraumatic stress disorder (PTSD). We hypothesize that
      among patients with PNEEs and PTSD, the nature of the traumatic experience
      leading to PTSD has an association with the clinical manifestations of PNEEs. We
      found that the presence of PTSD, in general, did not demonstrate significant
      association with any particular PNEE semiology in a veterans population. However,
      11 of 12 (91.7%) subjects with PNEEs and specifically combat-related PTSD showed
      significant predilection for hypomotor or nonmotor PNEEs, as compared to 5 of 12
      (41.7%) subjects with PNEE and non-combat-related PTSD (P=0.027). Between these
      two subgroups of subjects with PTSD, there were no statistical differences in the
      rating of service-connected disability for "seizures," presence of psychiatric
      history other than PTSD, marital status, substance abuse history, and use of
      antiepileptic drugs. Timely diagnosis of PNEEs can be especially relevant to
      veterans with combat-related PTSD, whose PNEE manifestations may be subtle and
      erringly overlooked.

PMID- 20045668
TI  - Lumbar hibernoma: a rare cause of soft tissue swelling.

PMID- 20045669
TI  - Larvicidal activities of ginger (Zingiber officinale) against Angiostrongylus
      cantonensis.
AB  - In this study, we investigated the anthelmintic activity of [6]-gingerol, [10]
      shogaol, [10]-gingerol, [6]-shogaol and hexahydrocurcumin, a constituent isolate
      from the roots of ginger (Zingiber officinale), for the parasite Angiostrongylus
      cantonensis. This study found that the above constituents killed A. cantonensis
      larvae or reduced their spontaneous movements in a time- and dose-dependent
      manner. The larvicidal effect or ability to halt spontaneous parasite movement of
      [10]-shogaol, [6]-gingerol, [10]-gingerol, [6]-shogaol and hexahydrocurcumin at
      various concentrations was reached from 24 to 72 h, respectively. Further
      investigation to determine minimal effective doses of [10]-gingerol and
      hexahydrocurcumin revealed [10]-gingerol to have a greater maximum larvicidal
      effect and loss of spontaneous movements than hexahydrocurcumin, mebendazole and
      albendazole. These constituents of ginger showed effects against DPPH and peroxyl
      radical under larvicidal effect. Together, these findings suggest that these
      constituents of ginger might be used as larvicidal agents against A. cantonensis.

PMID- 20045670
TI  - In-gel protein phosphatase assay using fluorogenic substrates.
AB  - We developed a method for the detection of phosphatase activity using fluorogenic
      substrates after polyacrylamide gel electrophoresis. When phosphatases such as
      Ca2+/calmodulin-dependent protein kinase phosphatase (CaMKP), protein phosphatase
      2C (PP2C), protein phosphatase 5 (PP5), and alkaline phosphatase were resolved by
      polyacrylamide gel electrophoresis in the absence of SDS and the gel was
      incubated with a fluorogenic substrate such as 4-methylumbelliferyl phosphate
      (MUP), all of these phosphatase activities could be detected in situ. Although
      6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) as well as MUP could be used
      as a fluorogenic substrate for an in-gel assay, MUP exhibited lower background
      fluorescence. Using this procedure, several fluorescent bands that correspond to
      endogenous phosphatases were observed after electrophoresis of various crude
      samples. The in-gel phosphatase assay could also be used to detect protein
      phosphatases resolved by SDS-polyacrylamide gel electrophoresis. In this case,
      however, the denaturation/renaturation process of resolved proteins was necessary
      for the detection of phosphatase activity. This procedure could be used for
      detection of renaturable protein phosphatases such as CaMKP and some other
      phosphatases expressed in cell extracts. The present fluorescent in-gel
      phosphatase assay is very useful, since no radioactive compounds or no special
      apparatus are required.

PMID- 20045671
TI  - A high recovery microsampling device based on a microdialysis probe for peptide
      sampling.
AB  - A high recovery microsampling probe based on microdialysis was devised. The new
      probe showed a high recovery (100%) of peptides in vitro at different perfusion
      flow rates (0.1-1.0 microl/min). At a high flow rate, 1.0 microl/min, a 10-fold
      increased in recovery of peptides compared to the conventional microdialysis
      probe was achieved. A probe made of a low molecular weight cutoff membrane is
      suitable for filtering off proteins. The new probe can be a useful tool for high
      recovery of peptides from living tissues.

PMID- 20045672
TI  - A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of
      thrombin.
AB  - To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target
      cell receptors, various cell-cell-fusion assays have been developed. In the
      present study, we established a novel fusion system. In this system, the
      expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the
      target cells was used to evaluate cell fusion event. Simultaneously,
      constitutively expressed Renilla luciferase (RL) gene was used to monitor
      effector cell number and viability. FL gave a wider dynamic range than other
      known reporters and the introduction of RL made the assay accurate and
      reproducible. This system is especially beneficial for investigation of potential
      entry-influencing agents, for its power of ruling out the false inhibition or
      enhancement caused by the artificial cell-number variation. As a case study, we
      applied this fusion system to observe the effect of a serine protease, thrombin,
      on HIV Env-mediated cell-cell fusion and have found the fusion enhancement
      activity of thrombin over two R5-tropic HIV strains.

PMID- 20045673
TI  - NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma.
AB  - Oral cancer is one of the most common cancers worldwide, and squamous-cell
      carcinoma (OSCC) is the most common phenotype of oral cancer. Although patients
      with OSCC have poor survival rates and a high incidence of metastasis, the
      molecular mechanisms of OSCC development have not yet been elucidated. This study
      investigated whether N-myc downstream-regulated gene 2 (NDRG2) contributes to the
      carcinogenesis of OSCC, as NDRG2 is reported to be a candidate tumor-suppressor
      gene in a wide variety of cancers. The down-regulation of NDRG2 mRNA, which was
      dependent on promoter methylation, was seen in the majority of OSCC cases and in
      several cases of precancerous leukoplakia with dysplasia. Induction of NDRG2
      expression in an HSC-3/OSCC cell line significantly inhibited cell proliferation
      and decreased colony formation ability on soft agar. The majority of OSCC cell
      lines showed an activation of PI3K/Akt signaling, and enforced expression of
      NDRG2 in HSC-3 cells decreased the level of phosphorylated Akt at Serine 473 (p
      Akt). Immunohistochemical p-Akt staining was detected in 56.5% of the OSCC
      tumors, and 80.4% of the tumors were negative for NDRG2 staining. Moreover,
      positive p-Akt staining was inversely correlated with decreased NDRG2 expression
      in OSCC tumors with moderate to poor differentiation (p<0.005). Therefore, NDRG2
      is a candidate tumor-suppressor gene for OSCC development and probably
      contributes to the tumorigenesis of OSCC partly via the modulation of Akt
      signaling.

PMID- 20045674
TI  - Glucosamine induces autophagy via an mTOR-independent pathway.
AB  - Autophagy is a cellular process that nonspecifically degrades cytosolic
      components and is involved in many cellular responses. We found that amino sugars
      with a free amino group such as glucosamine, galactosamine and mannosamine
      induced autophagy via an mTOR-independent pathway. Glucosamine-induced autophagy
      at concentrations of at least 500 microM to over 40 mM. In the presence of 40 mM
      glucosamine, autophagy induction was initiated at 6h and reached a plateau at 36
      h. Glucosamine-induced autophagy could remove accumulated ubiquitin-conjugated
      proteins as well as 79-glutamine repeats. Therefore, orally administered
      glucosamine could contribute to the prevention of neurodegenerative diseases and
      promotion of antiaging effects.

PMID- 20045675
TI  - Plasma membrane calcium pump and sodium-calcium exchanger in maintenance and
      control of calcium concentrations in platelets.
AB  - The purpose of this research was to elucidate the activity of the mechanisms
      responsible for control of cytosolic calcium concentration in platelets by
      modeling the time-course of the concentration changing in response to discharge
      of the intracellular stores or store-operated calcium entry (SOCE). The
      parameters estimated as a result of model fitting to experimental data are
      related to physiological or pathological state of the cells. It has been shown
      that: (a) the time-course is determined by the passive calcium fluxes and
      activities of the corresponding mechanisms; (b) the decline in the concentration
      (after its rise) develops due to activity of plasma membrane calcium ATPase
      (PMCA) both in the case of discharge of the stores of platelets contained in
      calcium-free medium and in the case of SOCE; (c) impulsive extrusion of calcium
      in response to its sudden influx, presumably, is the main function of PMCA; (d)
      the function of sodium-calcium exchanger (NCX) is to extrude calcium excess by
      permanent counteracting its influx.

PMID- 20045676
TI  - St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition
      of the protein kinase Cgamma and epsilon activity.
AB  - Current pharmacological treatments for neuropathic pain have limited efficacy and
      severe side-effect limitations. St. John's Wort (SJW) is a medicinal plant,
      mainly used as antidepressant, with a favourable side-effect profile. We here
      demonstrate the ability of SJW to relieve neuropathic pain in rat models. The
      antihyperalgesic profile and mechanism of action of SJW and its main components
      were studied in two rat models of neuropathic pain: the chronic constriction
      injury and the repeated administration of oxaliplatin. SJW, acutely administered
      at low doses (30-60 mg kg(-1) p.o.), reversed mechanical hyperalgesia with a
      prolonged effect, being effective up to 180 min after injection. Further
      examinations of the SJW main components revealed that hyperforin and hypericin
      were responsible for the antihyperalgesic properties whereas flavonoids were
      ineffective. The effect of SJW on the PKC expression and activation was
      investigated in the periaqueductal grey (PAG) area by immunoblotting experiments.
      Mechanistic studies showed a robust over-expression and hyperphosphorylation of
      the PKCgamma (227.0+/-15.0% of control) and PKCepsilon (213.9+/-17.0) isoforms in
      the rat PAG area. A single oral administration of SJW produced a significant
      decrease of the PKCgamma (131.8+/-10.0) and PKCepsilon (105.2+/-12.0)
      phosphorylation in the PAG area due to the presence of hypericin. Furthermore,
      SJW showed a dual mechanism of action since hyperforin antinociception involves
      an opioid-dependent pathway. Rats undergoing treatment with SJW and purified
      components did not show any behavioural side effects or signs of altered
      locomotor activity. Our results indicate SJW as a prolonged antihyperalgesic
      treatment through inhibition of PKC isoforms and their phosphorylation.

PMID- 20045677
TI  - Human visual system automatically represents large-scale sequential regularities.
AB  - Our brain recordings reveal that large-scale sequential regularities defined
      across non-adjacent stimuli can be automatically represented in visual sensory
      memory. To show that, we adopted an auditory paradigm developed by Sussman, E.,
      Ritter, W., and Vaughan, H. G. Jr. (1998). Predictability of stimulus deviance
      and the mismatch negativity. NeuroReport, 9, 4167-4170, Sussman, E., and
      Gumenyuk, V. (2005). Organization of sequential sounds in auditory memory.
      NeuroReport, 16, 1519-1523 to the visual domain by presenting task-irrelevant
      infrequent luminance-deviant stimuli (D, 20%) inserted among task-irrelevant
      frequent stimuli being of standard luminance (S, 80%) in randomized (randomized
      condition, SSSDSSSSSDSSSSD...) and fixed manners (fixed condition,
      SSSSDSSSSDSSSSD...). Comparing the visual mismatch negativity (visual MMN), an
      event-related brain potential (ERP) index of memory-mismatch processes in human
      visual sensory system, revealed that visual MMN elicited by deviant stimuli was
      reduced in the fixed compared to the randomized condition. Thus, the large-scale
      sequential regularity being present in the fixed condition (SSSSD) must have been
      represented in visual sensory memory. Interestingly, this effect did not occur in
      conditions with stimulus-onset asynchronies (SOAs) of 480 and 800 ms but was
      confined to the 160-ms SOA condition supporting the hypothesis that large-scale
      regularity extraction was based on perceptual grouping of the five successive
      stimuli defining the regularity.

PMID- 20045678
TI  - Epithelial reorganization events during late extraembryonic development in a
      hemimetabolous insect.
AB  - As extra-embryonic tissues, the amnion and serosa are not considered to
      contribute materially to the insect embryo, yet they must execute an array of
      morphogenetic movements before they are dispensable. In hemimetabolous insects,
      these movements have been known for over a century, but they have remained
      virtually unexamined. This study addresses late extraembryonic morphogenesis in
      the milkweed bug, Oncopeltus fasciatus. Cell shape changes and apoptosis profiles
      are used to characterize the membranes as they undergo a large repertoire of
      final reorganizational events that reposition the embryo (katatrepsis), and
      eliminate the membranes themselves in an ordered fashion (dorsal closure). A
      number of key features were identified. First, amnion-serosa "fusion" involves
      localized apoptosis in the amnion and the formation of a supracellular actin
      purse string at the amnion-serosa border. During katatrepsis, a 'focus' of
      serosal cells undergoes precocious columnarization and may serve as an anchor for
      contraction. Lastly, dorsal closure involves novel modifications of the amnion
      and embryonic flank that are without counterpart during the well-known process of
      dorsal closure in the fruit fly Drosophila melanogaster. These data also address
      the long-standing question of the final fate of the amnion: it undergoes
      apoptosis during dorsal closure and thus is likely to be solely extraembryonic.

PMID- 20045679
TI  - Developmental gene regulation in the era of genomics.
AB  - Genetic experiments over the last few decades have identified many developmental
      control genes critical for pattern formation and cell fate specification during
      the development of multicellular organisms. A large fraction of these genes
      encode transcription factors and signaling molecules, show highly dynamic
      expression patterns during development, and are deeply evolutionarily conserved
      and deregulated in various human diseases such as cancer. Because of their
      importance in development, evolution, and disease, a fundamental question in
      biology is how these developmental control genes are regulated in such an
      extensive and precise fashion. Using genomics methods, it has become clear that
      developmental control genes are a distinct group of genes with special regulatory
      characteristics. However, a systematic analysis of these characteristics has not
      been presented. Here we review how developmental control genes were discovered,
      evaluate their genome-wide regulation and gene structure, discuss emerging
      evidence for their mode of regulation, and estimate their overall abundance in
      the genome. Understanding the global regulation of developmental control genes
      may provide a new perspective on development in the era genomics.

PMID- 20045680
TI  - Distinct enhancers at the Pax3 locus can function redundantly to regulate neural
      tube and neural crest expressions.
AB  - Pax3 is a transcription factor expressed in somitic mesoderm, dorsal neural tube
      and pre-migratory neural crest during embryonic development. We have previously
      identified cis-acting enhancer elements within the proximal upstream genomic
      region of Pax3 that are sufficient to direct functional expression of Pax3 in
      neural crest. These elements direct expression of a reporter gene to pre
      migratory neural crest in transgenic mice, and transgenic expression of a Pax3
      cDNA using these elements is sufficient to rescue neural crest development in
      mice otherwise lacking endogenous Pax3. We show here that deletion of these
      enhancer sequences by homologous recombination is insufficient to abrogate neural
      crest expression of Pax3 and results in viable mice. We identify a distinct
      enhancer in the fourth intron that is also capable of mediating neural crest
      expression in transgenic mice and zebrafish. Our analysis suggests the existence
      of functionally redundant neural crest enhancer modules for Pax3.

PMID- 20045681
TI  - Lack of maternal Heat Shock Factor 1 results in multiple cellular and
      developmental defects, including mitochondrial damage and altered redox
      homeostasis, and leads to reduced survival of mammalian oocytes and embryos.
AB  - Heat Shock Factor 1 (HSF1) is a transcription factor whose loss of function
      results in the inability of Hsf1(-/-) females to produce viable embryos, as a
      consequence of early developmental arrest. We previously demonstrated that
      maternal HSF1 is required in oocytes to regulate expression of chaperones, in
      particular Hsp90alpha, and is essential for the progression of meiotic
      maturation. In the present work, we used comparative morphological and
      biochemical analytic approaches to better understand how Hsf1(-/-) oocytes
      undergo irreversible cell death. We found that the metaphase II arrest in mature
      oocytes, cortical granule exocytosis and formation of pronuclei in zygotes were
      all impaired in Hsf1(-/-) mutants. Although oogenesis generated fully grown
      oocytes in follicles, intra-ovarian Hsf1(-/-) oocytes displayed ultrastructural
      abnormalities and contained dysfunctional mitochondria as well as elevated
      oxidant load. Finally, the apoptotic effector, caspase-3, was activated in most
      mutant oocytes and embryos, reflecting their commitment to apoptosis. In
      conclusion, our study shows that early post-ovulation events are particularly
      sensitive to oxidant insult, which abrogates the developmental competence of HSF1
      depleted oocytes. They also reveal that Hsf1 knock-out mice constitute a genetic
      model that can be used to evaluate the importance of redox homeostasis in
      oocytes.

PMID- 20045682
TI  - beta-catenin plays a central role in setting up the head organizer in hydra.
AB  - In an adult hydra the head organizer, located in the hypostome, is constantly
      active in maintaining the structure of the animal in the context of its steady
      state tissue dynamics. Several Wnt genes, TCF, and elevated levels of beta
      catenin are expressed in the hypostome as well as during the formation of a new
      organizer region in developing buds suggesting they play a role in the organizer.
      Transgenic hydra were generated in which a modified hydra beta-catenin gene
      driven by an actin promoter is continuously expressed at a high level throughout
      the animal. These animals formed heads and secondary axes in multiple locations
      along the body column. Transplantation experiments indicate they have a high and
      stable level of head organizer activity throughout the body columns. However,
      none of the Wnt genes are expressed in the body columns of these transgenic
      animals. Further, in alsterpaullone-treated animals, which results in a transient
      rise in head organizer activity throughout the body column, the time of
      expression of the Wnt genes is much shorter than the time of the elevated level
      of head inducing activity. These results for the first time provide direct
      functional evidence that beta-catenin plays a crucial role in the maintenance and
      activity of the head organizer and suggest that Wnt ligands may be required only
      for the initiation but not in maintenance of the organizer in Hydra.

PMID- 20045683
TI  - Cell cycle defects in polyhomeotic mutants are caused by abrogation of the DNA
      damage checkpoint.
AB  - Polycomb group (PcG) genes are required for heritable silencing of target genes.
      Many PcG mutants have chromatin bridges and other mitotic defects in early
      embryos. These phenotypes can arise from defects in S phase or mitosis, so the
      phenotype does not show when PcG proteins act in cell cycle regulation. We
      analyzed the cell cycle role of the proximal subunit of Polyhomeotic (PhP) in
      Drosophila. Time-lapse imaging reveals that chromatin bridges formed during
      mitosis are able to resolve but sometimes result in chromosome breakage.
      Chromosome bridging is also observed in canonical cell cycles occurring in larval
      brains and is therefore not unique to the rapid embryonic cycles. PhP colocalizes
      with chromatin in S phase but not in mitosis in early embryos, indicating a
      direct role in DNA synthesis. Time lapse imaging of ph(p) mutants reveals an
      acceleration of S phase, showing that ph(p) regulates S phase length. Like ph(p)
      mutations, mutations in DNA damage checkpoints result in S phase acceleration.
      Consistent with this model, mutations in ph do not affect DNA synthesis rates,
      but exhibit impaired ability to block cell cycle progression following exposure
      to gamma-rays. Our data show that the mitotic defects of ph(p) are caused by
      defects in the DNA damage response that occurs after DNA replication in S phase,
      and we propose that PhP has a direct role in DNA damage repair.

PMID- 20045685
TI  - Coral emx-Am can substitute for Drosophila empty spiracles function in head, but
      not brain development.
AB  - The ems/Emx genes encode homeodomain transcription factors that have conserved
      actions in anterior embryonic patterning in bilaterian animals ranging from
      insects to mammals. Recently, genes of the ems/Emx family have been identified in
      cnidarians raising the possibility that some of their developmental functions
      might be conserved throughout the Eumetazoa. To determine to what extent
      functions of a cnidarian ems/Emx protein have been retained across phyla, we
      carried out cross-phylum rescue expression experiments in which the coral
      Acropora emx-Am gene was misexpressed in Drosophila ems mutants. Our findings
      demonstrate that coral emx-Am can substitute for fly ems in embryonic head
      development and rescue the open head defect and the loss of segmental engrailed
      expression domains in Drosophila ems mutants. In contrast, the coral emx-Am gene
      can not substitute for fly ems in embryonic brain development. Even when a
      hexapeptide motif of the type present in the Drosophila ems gene is inserted into
      the coral emx-Am gene, rescue of the developmental brain defects in fly ems
      mutants fails. These findings have implications for understanding the
      evolutionary origins of head versus brain patterning mechanisms.

PMID- 20045684
TI  - Chromatin insulator and the promoter targeting sequence modulate the timing of
      long-range enhancer-promoter interactions in the Drosophila embryo.
AB  - The homeotic genes are essential to the patterning of the anterior-posterior axis
      along the developing Drosophila embryo. The expression timing and levels of these
      genes are crucial for the correct specification of segmental identity. The
      Abdominal-B (Abd-B) gene is first detected in the most posterior abdominal
      segments at high levels and gradually appears in progressively anterior abdominal
      segments in lower amounts. Regulatory mutations affecting this expression pattern
      produce homeotic transformations in the abdomen. The promoter targeting sequences
      (PTS) from Abd-B locus overcome the enhancer blocking effect of insulators and
      facilitate long-range enhancer-promoter interactions in transgenic flies (1, 2).
      In this study, we found that transgene activation by the IAB5 enhancer can be
      delayed by inserting a 9.5 kb 3' Abd-B regulatory region containing the
      Frontabdominal-8 (Fab-8) insulator and the PTS element. We found that the delay
      is caused by the PTS and an insulator, and it is not specific to the enhancer or
      the promoter tested. Based on these findings, we hypothesize that the delay of
      remote enhancers is responsible for the Abd-B expression pattern, which is at
      least in part due to the regulatory activities of the PTS elements and chromatin
      boundaries.

PMID- 20045687
TI  - The small ubiquitin-like modifier (SUMO) is essential in cell cycle regulation in
      Trypanosoma brucei.
AB  - SUMO, a reversible post-translational protein modifier, plays important roles in
      many processes of higher eukaryotic cell life. Although SUMO has been identified
      in many eukaryotes, SUMO and SUMO system are still unknown in some eukaryotic
      unicellular organisms, such as Trypanosoma brucei (T. brucei). In this study,
      only one SUMO homologue (TbSUMO) was identified in T. brucei. Expression of
      TbSUMO was knocked down by using RNA interference technique in procyclic-form T.
      brucei. The growth of TbSUMO-deficient cells was significantly inhibited. TbSUMO
      deficient cells were arrested in G2/M phase accompanied with an obvious increase
      of 0N1K cells (zoids), and failed in chromosome segregation. These results
      indicate that TbSUMO is essential in cell cycle regulation, with one important
      role in mitosis. Meanwhile, the enrichment of zoids suggests the inhibition of
      mitosis does not prevent the cell division in procyclic-form T. brucei. HA-tagged
      TbSUMO was overexpressed in T. brucei and was shown to be localized to the
      nucleus through the whole cell cycle, further revealing its distinguished
      functions in nucleus. All these accumulated data imply that a SUMO system
      essential for regulating cell cycle progression might exist in the procyclic-form
      T. brucei.

PMID- 20045686
TI  - Mago Nashi, Tsunagi/Y14, and Ranshi form a complex that influences oocyte
      differentiation in Drosophila melanogaster.
AB  - During Drosophila melanogaster oogenesis, a germline stem cell divides forming a
      cyst of 16 interconnected cells. One cell enters the oogenic pathway, and the
      remaining 15 differentiate as nurse cells. Although directed transport and
      localization of oocyte differentiation factors within the single cell are
      indispensible for selection, maintenance, and differentiation of the oocyte, the
      mechanisms regulating these events are poorly understood. Mago Nashi and
      Tsunagi/Y14, core components of the exon junction complex (a multiprotein complex
      assembled on spliced RNAs), are essential for restricting oocyte fate to a single
      cell and for localization of oskar mRNA. Here we provide evidence that Mago Nashi
      and Tsunagi/Y14 form an oogenic complex with Ranshi, a protein with a zinc finger
      associated domain and zinc finger domains. Genetic analyses of ranshi reveal that
      (1) 16-cell cysts are formed, (2) two cells retain synaptonemal complexes, (3)
      all cells have endoreplicated DNA (as observed in nurse cells), and (4) oocyte
      specific cytoplasmic markers accumulate and persist within a single cell but are
      not localized within the posterior pole of the presumptive oocyte. Our results
      indicate that Ranshi interacts with the exon junction complex to localize
      components essential for oocyte differentiation within the posterior pole of the
      presumptive oocyte.

PMID- 20045688
TI  - Paragonimus westermani: identification and characterization of the fasciclin I
      domain-containing protein.
AB  - Paragonimus westermani is a trematode parasite that causes inflammatory lung
      disease as well as systemic infections in carnivorous mammals. The interaction of
      the parasite with host cells and paired worms is initiated by adhesion and plays
      an important role in parasite proliferation and differentiation. In this study,
      we isolated a cDNA encoding a P. westermani fasciclin I domain-containing protein
      (Pwfas-I). The fasiclin-I domain is suggested to be involved in cell adhesion,
      migration, and differentiation. Immunohistochemical analysis of P. westermani
      adult worms with polyclonal anti-Pwfas-I serum revealed immunoreactivity in the
      egg shells and the cells lining the sub-tegumental layer of adult worm throughout
      the contact regions of the cyst wall and paired worms. Using cell adhesion and
      spreading assays, we showed that Pwfas-I supports cell adhesion and spreading.
      Furthermore, we determined that the alphanubeta5 integrin was a functional
      receptor for the Pwfas-I. Taken together, these results suggest that Pwfas-I may
      be functional for the modulation of cell adhesion via binding with alphanubeta5
      integrin in the extracellular matrix of Paragonimus.

PMID- 20045689
TI  - Entamoeba invadens, encystation process and enolase.
AB  - The reptilian parasite Entamoeba invadens is accepted as a model for the study of
      the Entamoeba encystation process. Here we describe the production and
      characterization of a mAb (B4F2), generated against a component of the E.
      invadens cyst wall. This mAb specifically recognizes a 48-kDa protein present in
      cytoplasmic vesicles of cells encysting for 24 h. In mature cysts (96 h), the
      antigen was detected on the cyst surface. By two-dimensional electrophoresis and
      mass spectrometry analysis, the B4F2 specific antigen was identified as enolase.
      Levels of enolase mRNA were increased in encysting cells and the B4F2 mAb was
      found to inhibit cyst formation. Therefore, these results strongly suggest a new
      role for enolase in E. invadens encystation, and the B4F2 mAb will be useful tool
      to study its role in the differentiation process.

PMID- 20045690
TI  - Rhipicephalus (Boophilus) microplus: clotting time in tick-infested skin varies
      according to local inflammation and gene expression patterns in tick salivary
      glands.
AB  - Ticks deposit saliva at the site of their attachment to a host in order to
      inhibit haemostasis, inflammation and innate and adaptive immune responses. The
      anti-haemostatic properties of tick saliva have been described by many studies,
      but few show that tick infestations or its anti-haemostatic components exert
      systemic effects in vivo. In the present study, we extended these observations
      and show that, compared with normal skin, bovine hosts that are genetically
      susceptible to tick infestations present an increase in the clotting time of
      blood collected from the immediate vicinity of haemorrhagic feeding pools in skin
      infested with different developmental stages of Rhipicepahlus microplus;
      conversely, we determined that clotting time of tick-infested skin from
      genetically resistant bovines was shorter than that of normal skin. Coagulation
      and inflammation have many components in common and we determined that in
      resistant bovines, eosinophils and basophils, which are known to contain tissue
      factor, are recruited in greater numbers to the inflammatory site of tick bites
      than in susceptible hosts. Finally, we correlated the observed differences in
      clotting times with the expression profiles of transcripts for putative anti
      haemostatic proteins in different developmental stages of R. microplus fed on
      genetically susceptible and resistant hosts: we determined that transcripts
      coding for proteins similar to these molecules are overrepresented in salivary
      glands from nymphs and males fed on susceptible bovines. Our data indicate that
      ticks are able to modulate their host's local haemostatic reactions. In the
      resistant phenotype, larger amounts of inflammatory cells are recruited and
      expression of anti-coagulant molecules is decreased tick salivary glands,
      features that can hamper the tick's blood meal.

PMID- 20045691
TI  - The effect of levamisole and levamisole+vitamin C on oxidative damage in rats
      naturally infected with Syphacia muris.
AB  - This study was performed to determine the effects of levamisole and
      levamisole+vitamin C against Syphacia muris naturally infection in rats and to
      detect its effect on the oxidative parameters in blood and tissues of host. For
      this purpose, natural infection was diagnosed using the cellophane tape method on
      the perianal region of rats. Infected rats (total 18) were divided into three
      groups. On the other hand six without helminth rats were used in this study as
      negative control group. Group 2 was given an orally levamisole HCl treatment with
      gastric gavage at a dose level of 20mg/kg body weight in distilled water, every
      alternate day. Group 3 was given levamisole HCl via gastric gavage at a dose
      level of 20mg/kg and vitamin C was given 1g/L added to the drinking water. All
      the treatments continued for a period of 7 days. As a result; levamisole
      administered to rats at dose of 20mg/kg orally 98.34% was found to be effective
      against adult S. muris in the rats. In addition to levamisole+vitamin C is
      effective to alleviate the oxidative damage in rats infected with S. muris.

PMID- 20045692
TI  - Acanthamoeba castellanii Neff: In vitro activity against the trophozoite stage of
      a natural sesquiterpene and a synthetic cobalt(II)-lapachol complex.
AB  - In this study, the in vitro activities of a natural sesquiterpene, alpha
      cyperotundone, isolated from the root bark of Maytenus retusa and a cobalt(II)
      complex of a natural occurring prenyl hydroxynaphthoquinone (lapachol) were
      evaluated against the trophozoite stage of Acanthamoeba castellanii Neff using a
      previously developed colorimetric 96-well microtiter plate assay, based on the
      oxido-reduction of Alamar Blue(R). The obtained activities showed that these two
      compounds were able to inhibit the in vitro growth of the amoebae at relatively
      low concentrations. Further identification of the molecular targets of these
      products and their effects on acanthamoebae should be determined to evaluate
      their possible therapeutic use.

PMID- 20045693
TI  - Entamoeba histolytica: identification and partial characterization of alpha
      mannosidase activity.
AB  - Despite their well recognized importance in pathogenesis of Entamoeba histolytica
      there are few studies dealing with the assembly and secretion of glycoproteins
      that participate in the adhesion to target cells and in the dissemination of the
      parasite in infected tissues. Some of these studies refer to the identification
      and, in some cases, the characterization of glycosyl transferases and
      glycosidases involved in the biosynthesis of these macromolecules as well as to
      compartments involved in the amoeba dolichol-linked glycosylation pathway. While
      an N-glycan trimming alpha-mannosidase has been demonstrated in E. histolytica,
      little is known on its cellular distribution and properties. Here we describe the
      presence and partial biochemical characterization of soluble and MMF-associated
      forms of alpha-mannosidase and the separation of at least three internal membrane
      structures enriched with this glycosidase. Results are discussed in terms of the
      possible identity of alpha-mannosidase activity and the potential precursor
      product relationship between the two enzyme forms.

PMID- 20045694
TI  - Leishmania amazonensis: heme stimulates (Na(+)+K(+))ATPase activity via
      phosphatidylinositol-specific phospholipase C/protein kinase C-like (PI-PLC/PKC)
      signaling pathways.
AB  - In the present paper we studied the involvement of the phosphatidylinositol
      specific PLC (PI-PLC)/protein kinase C (PKC) pathway in (Na(+)+K(+))ATPase
      stimulation by heme in Leishmania amazonensis promastigotes. Heme stimulated the
      PKC-like activity with a concentration of 50nM. Interestingly, the maximal
      stimulation of the PKC-like activity promoted by phorbol ester was of the same
      magnitude promoted by heme. However, the stimulatory effect of heme is completely
      abolished by ET-18-OCH(3) and U73122, specific inhibitors of PI-PLC.
      (Na(+)+K(+))ATPase activity is increased in the presence of increased
      concentrations of heme, being maximally affected at 50nM. This effect was
      completely reversed by 10nM calphostin C, an inhibitor of PKC. Thus, the effect
      of 50nM heme on (Na(+)+K(+))ATPase activity is completely abolished by ET-18
      OCH(3) and U73122. Taken together, these results demonstrate that the heme
      receptor mediates the stimulatory effect of heme on the (Na(+)+K(+))ATPase
      activity through a PI-PLC/PKC signaling pathway.

PMID- 20045695
TI  - Schistosoma mansoni: egg-induced downregulation of hepatic stellate cell
      activation and fibrogenesis.
AB  - Eggs of Schistosoma mansoni trapped in human liver can lead to fibrosis. Since
      liver fibrosis requires activation of hepatic stellate cells (HSC) from a
      quiescent to a myofibroblastic phenotype, we investigated the effects of S.
      mansoni eggs on this process using in vitro co-cultures with human HSC and
      evaluated established biomarkers for activation and fibrosis. HSC demonstrate
      significantly reduced expression of alpha-smooth muscle actin (p<0.001),
      connective tissue growth factor (p<0.01) and type I collagen (p<0.001) but
      significantly increased expression of peroxisome proliferator-activated receptor
      gamma (p<0.01). Morphologically, HSC exhibited elongated fine cellular processes
      and reduced size, increased accumulation of lipid droplets and reduced expression
      and organization of alpha-smooth muscle actin and F-actin stress fibres.
      Additionally, schistosome eggs prevented the HSC fibrogenic response to exogenous
      transforming growth factor-beta. In summary, schistosome eggs blocked
      fibrogenesis in HSC, a finding which may have implications for our understanding
      of the fibrotic pathology in S. mansoni infections.

PMID- 20045696
TI  - Toxoplasma gondii: fluconazole and itraconazole activity against toxoplasmosis in
      a murine model.
AB  - Toxoplasma gondii is an important opportunistic pathogen affecting
      immunocompromised patients with AIDS. Toxoplasmic encephalitis is responsible for
      high morbidity and mortality. In this study, we investigated the activity of the
      antifungals fluconazole (FLZ) and itraconazole (ITZ) against T. gondii in mice
      infected with the Me49 strain. As previously reported for ITZ, FLZ also
      demonstrated a selective effect against T. gondii in vitro; the IC(50) values
      obtained for FLZ were 8.9 microM and 3.1 microM after 24h and 48 h of treatment,
      respectively. A 10-day treatment of mice with orally or intraperitoneally
      administered 20mg/kg/day FLZ showed a significant survival difference compared to
      untreated mice. The administration of 20mg/kg/day ITZ significantly reduced the
      brain cyst burden compared to untreated mice but did not exert significant
      protection against death. The results obtained in this work are rather promising
      as ITZ and FLZ are safe and low-cost drugs available on the market.

PMID- 20045697
TI  - Trichinella spiralis: immune response and protective immunity elicited by
      recombinant paramyosin formulated with different adjuvants.
AB  - Our previous studies showed that immunization with recombinant paramyosin from
      Trichinella spiralis (rTs-Pmy) formulated with Freund's adjuvant significantly
      reduced larval burden in mice after T. spiralis larval challenge. Since Freund's
      adjuvant is toxic and not a suitable adjuvant for clinical vaccine trials, we
      evaluated the ability of the adjuvants Montanide ISA206 and ISA720 to stimulate
      immune responses during rTs-Pmy immunization and to enhance protective immunity.
      The results revealed that immunization of BALB/c mice with rTs-Pmy formulated
      with either ISA206 or ISA720 triggered Th1 and Th2 immune responses similar to
      those produced by the conventional Freund's adjuvant formulation and also
      provided a similar level of protection against T. spiralis larval challenge. This
      indicates that the recombinant Ts-Pmy formulated with Montanide ISA206 or ISA720
      may be an effective and safety vaccine strategy for trichinellosis.

PMID- 20045698
TI  - Paramphistomum cervi: surface topography of the tegument of adult fluke.
AB  - Adult Paramphistomum cervi or rumen fluke are pear-shaped, slightly concave
      ventrally and convex dorsally. The worm measures about 5-13 mm in length and 2-5
      mm in width across the mid-section. As observed by scanning electron microscopy
      (SEM), the tegumental surface in all part of the body, appears highly corrugated
      with transverse folds alternating with grooves and is spineless. At high
      magnification, the surface of the fold is composed of microfolds or ridges
      separated by microgrooves or pits. Corrugations and invaginations of the ventral
      surface are also more extensive than on the dorsal surface of the body. Both
      anterior and posterior suckers have thick rims covered with transverse folds
      without spine. The genital pore is situated at the anterior third of the body.
      There are two types of sensory papillae on the surface: type 1 is bulbous in
      shape, measuring 10-15 microm in diameter at the base with nipple-like tips, and
      type 2 has a similar shape and size and also a short cilia on top. These sensory
      papillae usually occur in large clusters, each having between 5 and 20 units
      depending on the region of the body. Clusters of papillae on the ventral surface
      and around the anterior suckers tend to be more numerous and larger in size. The
      dorsal surface of the body has the least number of papillae.

PMID- 20045699
TI  - Neospora caninum: early immune response of rat mixed glial cultures after
      tachyzoites infection.
AB  - Neospora caninum causes neurologic disease in dogs and abortion in cattle. Little
      is known about the immune response of the CNS against this protozoan. The aim of
      this study was to evaluate production of IL-6, IL-10, TNF-alpha, IFN-gamma, and
      NO in rat mixed glial cell cultures infected by N. caninum. IFN-gamma was not
      observed. The mean cytokine released after 24 and 72 h of infection were 3.8+/
      0.6 and 3.7+/-0.6 pg TNF-alpha/mg protein and 2.7+/-0.69 and 4.1+/-0.64 pg IL
      10/mg protein, respectively, and more than 8.0 pg IL-6/mg protein for both time
      points. NO levels increased 24h post-infection (2.3+/-0.8 pg/mg protein) until 72
      h (4.2+/-1.1 pg/mg protein) and the number of tachyzoites reduced with the time.
      Our results show high levels of regulatory cytokines that may suppress the
      harmful effects of IFN-gamma; high levels of TNF-alpha and NO may represent an
      effective response by infected glial cells against N. caninum.

PMID- 20045700
TI  - Efficacy of linaclotide for patients with chronic constipation.
AB  - BACKGROUND & AIMS: Linaclotide is a minimally absorbed peptide agonist of the
      guanylate cyclase-C receptor that stimulates intestinal fluid secretion and
      transit and reduces pain in animal models. We assessed the safety and efficacy of
      a range of linaclotide doses in patients with chronic constipation. METHODS: We
      performed a multicenter, double-blind, placebo-controlled, parallel-group study
      of 310 patients with chronic constipation. Patients were randomly assigned to
      groups given 75, 150, 300, or 600 microg oral linaclotide or placebo once daily
      for 4 weeks. Symptom assessments included spontaneous bowel movements (SBMs),
      complete SBMs, stool consistency, straining, abdominal discomfort, and bloating.
      Severity of constipation, adequate relief of constipation, global relief of
      constipation, treatment satisfaction, quality of life, adverse events, clinical
      laboratory data, and electrocardiogram results were assessed. RESULTS: All doses
      of linaclotide improved the weekly rate of SBM (primary end point) compared with
      placebo; the increases in overall weekly number of SBMs from baseline were 2.6,
      3.3, 3.6, and 4.3 for linaclotide doses of 75, 150, 300, and 600 microg,
      respectively, compared with 1.5 for placebo (P < or = .05 for each pair-wise
      comparison of a linaclotide dose to placebo). Likewise, linaclotide significantly
      improved the weekly rate of complete SBM, stool consistency, straining, abdominal
      discomfort, bloating, global assessments, and quality of life. The most common
      and only dose-related adverse event was diarrhea (only 6 patients discontinued
      treatment because of diarrhea). CONCLUSIONS: Linaclotide therapy was associated
      with few adverse events and produced rapid and sustained improvement of bowel
      habits, abdominal symptoms, global relief, and quality of life in patients with
      chronic constipation.

PMID- 20045701
TI  - Altered brain structure in irritable bowel syndrome: potential contributions of
      pre-existing and disease-driven factors.
AB  - BACKGROUND & AIMS: Brain imaging studies have identified abnormal rectal-evoked
      responses and cortical thinning in patients with irritable bowel syndrome (IBS).
      However, it is not known whether these abnormalities are pre-existing or develop
      as result of long-term IBS. Therefore, we tested whether abnormal structural gray
      matter integrity in IBS correlates with individual disease symptoms, duration of
      the IBS, or the personality characteristic of pain catastrophizing. METHODS:
      Eleven IBS patients and 16 age-matched healthy subjects underwent structural
      magnetic resonance imaging. Voxel-based morphometry and cortical thickness
      analysis were used to identify abnormalities in subcortical and cortical regions,
      respectively, and their correlation to individual characteristics. RESULTS: The
      IBS group showed increased hypothalamic gray matter and cortical thinning in the
      anterior midcingulate cortex compared with controls, a strong negative
      correlation between dorsolateral prefrontal cortex thickness and pain
      catastrophizing, and a positive correlation between anterior insula thickness and
      pain duration. In the insula, there was cortical thinning in patients with short
      term IBS, but long-term IBS pain was associated with a more normal insula
      thickness. CONCLUSIONS: Our findings provide new insight into IBS and chronic
      pain through evidence for structural changes that could fit with functional
      abnormalities. We report that patients with IBS have increased hypothalamic gray
      matter, which may be related to the association among IBS, stress, and the
      hypothalamic-pituitary-adrenal axis. Furthermore, we have identified some
      supraspinal abnormalities that may be pre-existing and contribute to
      vulnerability, and others that may develop over time, possibly because of chronic
      abnormal inputs.

PMID- 20045702
TI  - On the correlation between continuum mechanics entities and cell activity in
      biological soft tissues: assessment of three possible criteria for cell
      controlled fibre reorientation in collagen gels and collagenous tissues.
AB  - The biomechanical behaviour of biological cells is of great importance in many
      physiological processes. One such process is the maintenance of fibrous networks,
      such as collagenous tissues. The activity of the fibre-producing cells in this
      type of tissue is very important, and a comprehensive material description needs
      to incorporate the activity of the cells. In biomechanics, continuum mechanics is
      often employed to describe deforming solids, and modelling can be much simplified
      if continuum mechanics entities, such as stress and strain, can be correlated
      with cell activity. To investigate this, a continuum mechanics framework is
      employed in which remodelling of a collagen gel is modelled. The remodelling is
      accomplished by fibroblasts, and the activity of the fibroblasts is linked to the
      continuum mechanics theory. The constitutive model for the collagen fabric is
      formulated in terms of a strain energy function, which includes a density
      function describing the distribution of the collagen fibre orientation. This
      density function evolves according to an evolution law, where fibroblasts
      reorient fibres towards the direction of increasing Cauchy stress, elastic
      deformation, or stiffness. The theoretical framework is applied to experimental
      results from collagen gels, where gels have undergone remodelling under both
      biaxial and uniaxial constraint. The analyses indicated that criteria 1 and 2
      (Cauchy stress and elastic deformations) are able to predict the collagen fibre
      distribution after remodelling, whereas criterion 3 (current stiffness) is not.
      This conclusion is, however, tentative and pertains, strictly speaking, only to
      fibre remodelling processes, and may not be valid for other types of cell
      activities.

PMID- 20045703
TI  - A mathematical model of cleavage.
AB  - In the present paper, we propose a mathematical model of cleavage. Cleavage is a
      process during the early stages of development in which the fertile egg undergoes
      repeated division keeping the cluster size almost constant. During the cleavage
      process individual cells repeat cell division in an orderly manner to form a
      blastula, however, the mechanism which achieves such a coordination is still not
      very clear. In the present research, we took sea urchin as an example and focused
      on the diffusion of chemical substances from the animal and vegetal pole. By
      considering chemotactic motion of the centrosomes, we constructed a mathematical
      model that describes the processes in the early stages of cleavage.

PMID- 20045704
TI  - A macroscopic ansatz to deduce the Hill relation.
AB  - In this study, we derive the hyperbolic force-velocity relation of concentric
      muscular contraction, first formulated empirically by A.V. Hill in 1938, from
      three essential model assumptions: (1) the structural assembly of three well
      known elements - i.e. active, parallel damping, and serial - fulfilling a force
      equilibrium, (2) the parallel damping coefficient explicitly depending on muscle
      force output and three parameters, and (3) the kinematic gearing ratio between
      active and serial element being assigned to a parameter. The energy source within
      the muscle represented by the force of the active element is an additional fifth
      parameter. As a result we find the Hill "constants" A and B as functions of our
      five model parameters. Using A and B values from literature on experimental data,
      we predict heat power release of our model. By calculating enthalpy rate and
      mechanical efficiency, we compare the model heat power to predictions from
      another Hill-type model, to Hill's original findings, and to findings from modern
      muscle heat measurements. We reconsider why the biggest share of heat rate during
      isometric contractions (maintenance heat) and the velocity-dependent heat rate
      during concentric contractions in addition to maintenance heat rate (shortening
      heat rate) may be traced back to the same mechanism represented by the kinematic
      gearing ratio. Namely, we suggest that the serial element transfers attachment
      detachment fluctuations of actin-myosin crossbridges within one sarcomere to
      others in the same sarcomere and to those in parallel and in series. Numerically,
      in case of negligible passive muscular damping, we find the ratio between A and
      isometric force (relative A) to depend exclusively on the kinematic gearing
      ratio, whereas the maintenance heat rate scales with the square of relative A.
      Moreover, this mechanical coupling internal to the muscle fibres may also be
      behind the macroscopic force dependency of the overall parallel damping
      coefficient.

PMID- 20045705
TI  - Extrinsic noise passing through a Michaelis-Menten reaction: a universal response
      of a genetic switch.
AB  - The study of biochemical pathways usually focuses on a small section of a protein
      interactions network. Two distinct sources contribute to the noise in such a
      system: intrinsic noise, inherent in the studied reactions, and extrinsic noise
      generated in other parts of the network or in the environment. We study the
      effect of extrinsic noise entering the system through a nonlinear uptake reaction
      which acts as a nonlinear filter. Varying input noise intensity varies the mean
      of the noise after the passage through the filter, which changes the stability
      properties of the system. The steady-state displacement due to small noise is
      independent on the kinetics of the system but it only depends on the nonlinearity
      of the input function. For monotonically increasing and concave input functions
      such as the Michaelis-Menten uptake rate, we give a simple argument based on the
      small-noise expansion, which enables qualitative predictions of the steady-state
      displacement only by inspection of experimental data: when weak and rapid noise
      enters the system through a Michaelis-Menten reaction, then the graph of the
      system's steady states vs. the mean of the input signal always shifts to the
      right as noise intensity increases. We test the predictions on two models of lac
      operon, where TMG/lactose uptake is driven by a Michaelis-Menten enzymatic
      process. We show that as a consequence of the steady state displacement due to
      fluctuations in extracellular TMG/lactose concentration the lac switch responds
      in an asymmetric manner: as noise intensity increases, switching off lactose
      metabolism becomes easier and switching it on becomes more difficult.

PMID- 20045706
TI  - De-routing neuronal precursors in the adult brain to sites of injury: role of the
      vasculature.
AB  - Neurogenesis in the adult brain occurs predominantly in the two regions, the
      subventricular zone (SVZ) bordering the lateral ventricle and subgranular zone
      (SGZ) of the hippocampus. The neuronal precursors are produced in the specialized
      microenvironment called neurovasculature niche. Recent evidences indicate that in
      addition to neurogenesis promoting environment, vasculature also serves as a
      substrate for migration for these newly generated cells. Importantly, under some
      pathological condition, including stroke, neurogenesis is enhanced in the adult
      brain. Newly generated neuronal precursors migrate to the sites of injury along
      the blood vessels and try to integrate to the damaged brain circuitry. This self
      healing capacity of the adult brain is, however, insufficient to produce a
      noticeable amelioration in the affected neuronal network since only a tiny
      proportion of cells succeed to integrate and survive. Here we review the
      mechanisms of neuronal recruitment into the post-stroke regions with particular
      attention to the guidance of neuronal precursors along the blood vessels. We also
      outline some of the molecular factors that have been used or have a potential to
      be employed to improve the cell recruitment into the sites of injury.

PMID- 20045708
TI  - Thyroid hormone prevents cognitive deficit in a mouse model of Alzheimer's
      disease.
AB  - This study aimed to examine the feasibility of using thyroid hormone (TH) as a
      therapeutic agent for Alzheimer's disease (AD). Mice were injected intra
      hippocampally aggregated amyloid beta-peptide (Abeta) to produce AD animal model.
      Intraperitoneal administration of l-thyroxine (L-T4) into Abeta-induced AD model
      mice prevented their cognitive impairment and improved their memory function. The
      mechanisms of L-T4 treating AD might be associated with regulating cholinergic
      function, protecting the brains of AD model mice against damage from free
      radicals, and rescuing hippocampal neurons from apoptosis. The results of the
      present study indicate that the use of TH has some therapeutic potential in AD.

PMID- 20045707
TI  - mGluR-mediated and endocannabinoid-dependent long-term depression in the hilar
      region of the rat dentate gyrus.
AB  - We report that bath application of the group I mGluR agonist (RS)-3,5
      dihydroxyphenylglycine (DHPG) causes acute inhibition of evoked IPSCs recorded
      from hilar mossy cells, and that significant long-term depression (LTD) of
      synaptic transmission remains following washout of DHPG. Subsequent experiments
      using minimal stimulation techniques revealed that expression of both acute and
      long-term effects of DHPG are restricted to a subset of GABAergic afferents that
      are also sensitive to depolarization-induced suppression of inhibition (DSI).
      Experiments with a selective CB1 antagonist and with transgenic animals lacking
      CB1 receptors indicate that all effects of DHPG, like DSI, depend on activation
      of CB1 receptors. Further work with selective mGluR antagonists suggests a direct
      involvement of mGluR1 receptors. Interestingly, we also report that induction of
      LTD under our experimental conditions does not require prior direct somatic
      depolarization via the patch pipette and does not appear to depend critically on
      the level of activity in incoming GABAergic afferents. Collectively, these
      results represent the first characterization of mGluR-mediated and
      endocannabinoid-dependent LTD in the hilar region of the dentate gyrus. The
      dentate gyrus is thus one of relatively few areas where this mechanism has
      clearly been demonstrated to induce long-term modulation of inhibitory synaptic
      transmission.

PMID- 20045709
TI  - The cardiotoxicity and myocyte damage caused by small molecule anticancer
      tyrosine kinase inhibitors is correlated with lack of target specificity.
AB  - The use of the new anticancer tyrosine kinase inhibitors (TKI) has revolutionized
      the treatment of certain cancers. However, the use of some of these results in
      cardiotoxicity. Large-scale profiling data recently made available for the
      binding of 7 of the 9 FDA-approved tyrosine kinase inhibitors to a panel of 317
      kinases has allowed us to correlate kinase inhibitor binding selectivity scores
      with TKI-induced damage to neonatal rat cardiac myocytes. The tyrosine kinase
      selectivity scores, but not the serine-threonine kinase scores, were highly
      correlated with the myocyte damaging effects of the TKIs. Additionally, we showed
      that damage to myocytes gave a good rank order correlation with clinical
      cardiotoxicity. Finally, strength of TKI binding to colony-stimulating factor 1
      receptor (CSF1R) was highly correlated with myocyte damage, thus possibly
      implicating this kinase in contributing to TKI-induced cardiotoxicity.

PMID- 20045710
TI  - Electrophysiological correlates of figure-ground segregation directly reflect
      perceptual saliency.
AB  - In a figure identification task, we investigated the influence of different
      visual cue configurations (spatial frequency, orientation or a combination of
      both) on the human EEG. Combining psychophysics with ERP and time-frequency
      analysis, we show that the neural response at about 200ms reflects perceptual
      saliency rather than physical cue contrast. Increasing saliency caused (i) a
      negative shift of the posterior P2 coinciding with a power decrease in the
      posterior theta-band and (ii) an amplitude and latency increase of the posterior
      P3. We demonstrate that visual cues interact for a percept that is non-linearly
      related to the physical figure-ground properties.

PMID- 20045711
TI  - The effect of age on compensation for a negative lens and recovery from lens
      induced myopia in tree shrews (Tupaia glis belangeri).
AB  - We examined in tree shrews the effect of age on the development of, and recovery
      from, myopia induced with a negative lens. Starting at 11, 16, 24, 35 or 48days
      after natural eye-opening (days of visual experience [VE]), juvenile tree shrews
      (n=5 per group) wore a monocular -5D lens for 11days. A long-term lens-wear group
      (n=6) began treatment at 16days of VE and wore the lens for 30days. A young adult
      group (n=5) began to wear a -5D lens between 93 and 107days of VE (mean+/-SD,
      100+/-6days of VE) and wore the lens for 29-54days (mean+/-SD, 41.8+/-9.8days).
      The recovery phase in all groups was started by discontinuing -5D lens wear.
      Contralateral control eyes in the three youngest groups were compared with a
      group of age-matched normal eyes and showed a small (<1D), transient myopic
      shift. The amount of myopia that developed during lens wear was measured as the
      difference between the treated and control eye refractions. After 11days of lens
      wear, the induced myopia was similar for the four younger groups (near full
      compensation: 11days, -5.1+/-0.4D; 16days, -4.7+/-0.3D; 24days, -4.9+/-0.4D;
      35days, -4.0+/-0.02) and slightly less in the oldest juvenile group (48days, 
      3.3+/-0.5D). The young adult animals developed -4.8+/-0.3D of myopia after a
      longer lens-wear period. The rate of compensation (D/day) was high in the 4
      youngest groups and decreased in the 48-day and young adult groups. The
      refractions of the long-term lens-wear juvenile group remained stable after
      compensating for the -5D lens. During recovery, all animals in the youngest group
      recovered fully (<1D residual myopia) within 7days. Examples of both rapid
      (<10days) and slow recovery (>12days) occurred in all age groups except the
      youngest. Every animal showed more rapid recovery (higher recovery slope) in the
      first 4days than afterward. One animal showed extremely slow recovery. Based on
      the time-course of myopia development observed in the youngest age groups, the
      start of the susceptible period for negative-lens wear is around 11-15days after
      eye opening; the rate of compensation remains high until approximately 35days of
      VE and then gradually declines. Compensation is stable with continued lens wear.
      The emmetropization mechanism, both for lens compensation and recovery, remains
      active into young adulthood. The time-course of recovery is more variable than
      that of compensation and seems to vary with age, with the amount of myopia
      (weakly) and with the individual animal.

PMID- 20045712
TI  - Efficient learning produces spontaneous neural repetition suppression in
      prefrontal cortex.
AB  - Our study focuses on the physiological effects of repetition on learning and
      working memory using an adaptation of Luria's Memory Word-Task (LMWT). We assess
      the hemodynamic response in dorsolateral prefrontal cortex (DLPFC) of 13 healthy
      subjects while completing LMWT. Free word recalls were acquired at the beginning,
      middle and end of the task. Behavioral results showed that all subjects could
      recall the complete word list by the 10th trial, which was considered as
      successful task accomplishment. We observed an attenuation of stimulus-evoked
      neural activity in prefrontal neurons. Our findings show that the temporal
      integration of efficient verbal learning is mediated by a mechanism known as
      neural repetition suppression (NRS). This mechanism facilitates cortical
      deactivation in DLPFC once learning is successfully completed. This cortical
      reorganization is interpreted as a progressive optimization of neural responses
      to produce a more efficient use of neural circuits. NRS could be considered one
      of the natural mechanisms involved in the processes of memory learning.

PMID- 20045713
TI  - Efficacy of whey protein gel networks as potential viability-enhancing scaffolds
      for cell immobilization of Lactobacillus rhamnosus GG.
AB  - This study investigated cell immobilization of Lactobacillus rhamnosus GG in
      three separate protein products: native, denatured and hydrolysed whey protein
      isolate (WPI). Treatments were assessed for their ability to enhance probiotic
      survival during storage, heat stress and ex vivo gastric incubation. Spatial
      distribution of probiotic cells within immobilized treatments was evaluated by
      atomic force and confocal scanning laser microscopy, while cell viability was
      enumerated by plate count and flow cytometry (FACS). Microscopic analysis of
      denatured treatments revealed an oasis of immobilized cells, phase-separated from
      the surrounding protein matrix; an environmental characteristic analogous to
      hydrolysed networks. Cell immobilization in hydrolysed and denatured WPI enhanced
      survival by 6.1+/-0.1 and 5.8+/-0.1 log10 cycles, respectively, following 14 day
      storage at 37 degrees C and both treatments generated thermal protection at 57
      degrees C (7.3+/-0.1 and 6.5+/-0.1 log(10) cfu/ml). Furthermore, denatured WPI
      enhanced probiotic protection (8.9+/-0.2 log(10) cfu/ml) following 3h gastric
      incubation at 37 degrees C. In conclusion, hydrolysed or denatured WPI were the
      most suitable matrices for cell immobilization, while native protein provided the
      weakest safeguard against thermal and acid stress, thus making it possible to
      envision whey protein gel networks as protective substrates for cell
      immobilization applications.

PMID- 20045714
TI  - hsp65 PCR-restriction analysis (PRA) with capillary electrophoresis in comparison
      to three other methods for identification of Mycobacterium species.
AB  - We developed a scheme for rapid identification of Mycobacterium species using an
      automated fluorescence capillary electrophoresis instrument. A 441-bp region of
      the hsp65 gene was examined using PCR-restriction analysis (PRA). The assay was
      initially evaluated on 38 reference strains. The observed sizes of restriction
      fragments were consistently smaller than the real sizes for each of the species
      as deduced from the sequence analysis (mean variance=7bp). Nevertheless, the
      obtained PRA patterns were highly reproducible and resulted in correct species
      identifications. A blind test was then successfully performed on 64 test isolates
      previously characterized by conventional biochemical methods, a commercial INNO
      LiPA Mycobacteria assay and/or sequence determination of the 5' end of 16S rRNA
      gene. A total of 14 of 64 isolates were erroneously identified by conventional
      methods (78% accuracy). In contrast, PRA performed very well in comparison with
      the LiPA (89% concordance) and especially with DNA sequencing (93.3% of
      concordant results). Also, PRA identified seven isolates representing five
      previously unreported hsp65 alleles. We conclude that hsp65 PRA based on
      automated capillary electrophoresis is a rapid, simple and reliable method for
      identification of mycobacteria.

PMID- 20045715
TI  - Improvement of cathepsin S detection using a designed FRET peptide based on
      putative natural substrates.
AB  - Cathepsin S is a lysosomal cysteine peptidase of the papain superfamily which is
      implicated in physiological and pathological states. The enzyme is highly
      expressed in antigen presenting cells and is thought to play an important role in
      the processing of the major histocompatibility complex (MHC) class II-associated
      invariant chain. In pathological processes, cathepsin S is associated with
      Alzheimer's disease, atherosclerosis and obesity and can be regarded as a
      potential target in related disorders. However, due to the broad substrate
      specificities of the lysosomal cathepsins, the specific detection of cathepsin S
      is difficult when other cathepsins are present. In an attempt to distinguish
      cathepsin S from other cathepsins we synthesized and tested fluorescence
      resonance energy transfer (FRET) peptides derived from two of its putative
      natural substrates, namely insulin beta-chain and class II-associated invariant
      chain (CLIP). The influence of ionic strength on the catalytic activity and the
      enzyme stability in neutral pH was also analyzed. Using data gathered from our
      study we developed a selective substrate for cathepsin S and establish the assay
      conditions to differentiate the enzyme from cathepsins L, B, V and K. The peptide
      Abz-LEQ-EDDnp (Abz=ortho-aminobenzoic acid; EDDnp=N-[2,4
      dinitrophenyl]ethylenediamine]) in 50mM sodium phosphate buffer, pH 7.4,
      containing 1M NaCl was hydrolyzed by cathepsin S with k(cat)/K(m) value of
      3585mM(-1)s(-1), and was resistant to hydrolysis by cathepsins L, V, K and B.
      Thus, we developed a sensitive and selective cathepsins S substrate that permits
      continuous measurement of the enzymatic activity even in crude tissue extracts.

PMID- 20045716
TI  - In vitro and in vivo antitumor effects of novel actinomycin D analogs with amino
      acid substituted in the cyclic depsipeptides.
AB  - The actinomycin D (AMD) analogs in which the D-valine residues (the second amino
      acid residue in the cyclic depsipeptide of AMD) and the N-methyl-L-valine
      residues (the fifth amino acid residue in the cyclic depsipeptide of AMD) were
      replaced with D-Phe or l- and D-forms N-methylvalines, N-methylisoleucine, N
      methylleucine, N-methylphenylalanine, N-methylalanine, and sarcosine were
      synthesized. The antimicrobial activity and cytotoxic activities of these
      compounds in vitro were investigated. The results showed that most D-valine
      substituted analogs had much lower antimicrobial activity and cytotoxic
      activities in vitro than AMD itself, but three N-methyl-L-valine substituted
      analogs had comparable or even more remarkable cytotoxic activities in vitro than
      AMD. Acute toxicities and antitumor effects of the N-methyl-L-valine substituted
      analogs in mice were also examined. The result showed that the acute toxicity of
      compound 4 L-methylleucine(5)-AMD analog is comparable to AMD itself and that of
      compound 3(L-Methylisoleucine(5)-AMD analog) is slightly more toxic, about 1.25
      fold than AMD. However, the acute toxicity of compound 5 D-methylleucine5-AMD
      analog is about 2-fold lower than AMD. This suggested that the N-methyl-D-amino
      acid replacement in the cyclic ring might play a vital role in their decreased
      acute toxicities, and perhaps the N-methyl-D-leucine substituent is more
      favorable, though there may be a slight loss of antitumor activity. This finding
      may be helpful for the design and development of more potent antitumor agents
      together with low acute toxicity, and suggests that the N-methyl-D-leucine
      substituent has the potential to be used as antitumor drug lead.

PMID- 20045717
TI  - Comparison of pituitary-adrenal responsiveness between insulin tolerance test and
      growth hormone-releasing peptide-2 test: a pilot study.
AB  - Insulin tolerance test (ITT) is the gold standard for assessing the hypothalamic
      pituitary-adrenal (HPA) function. GH-releasing peptide (GHRP)-2, which has a
      strong GH-stimulating activity, is useful for diagnosing GH deficiency as well as
      ITT. Additionally, GHRP-2 is also known to activate HPA axis. There have been no
      comparative studies of pituitary-adrenal responsiveness between GHRP-2 test and
      ITT in patients with hypothalamic/pituitary disease. To assess whether GHRP-2
      test could be an alternative to ITT for diagnosing HPA axis failure, both ITT and
      GHRP-2 test were performed in 15 patients suspected of hypopituitarism. A 100mug
      dose of GHRP-2 was administered intravenously and plasma ACTH and serum cortisol
      concentrations were measured. In ITT, a peak cortisol value over 18mug/dl is
      considered normal. Nine patients were diagnosed as HPA axis failure by ITT. Their
      median peak cortisol in GHRP-2 test was 11.4mug/ml. In 6 patients diagnosed as
      normal HPA axis status by ITT, their median peak cortisol in response to GHRP-2
      test was 21.4mug/dl, significantly higher (p=0.0032) than seen in patients
      diagnosed as HPA axis failure. There was a strong correlation between the peak
      cortisol in GHRP-2 test and ITT (r=0.817; p<0.0001). When the cut-off value for
      the peak cortisol in GHRP-2 test was set to 13-14mug/dl for diagnosing HPA axis
      failure, the specificity and sensitivity were 100% and 88.9%, respectively.
      Although further studies that include normal subjects are needed, these
      preliminary results suggest the possibility that GHRP-2 test may be an
      alternative to ITT for assessing HPA axis function.

PMID- 20045718
TI  - Spatial resolution of visual feedback affects variability and structure of
      isometric force.
AB  - The purpose of this study was to examine the effect of spatial resolution of
      visual feedback on the variability and structure of isometric force. We
      manipulated spatial resolution of the display by changing the number of possible
      feedback dot positions. Twelve healthy young adults (5 men, 7 women) attempted to
      apply a constant level of force normal to a load cell with the index finger using
      two types of visual displays. One display provided high spatial resolution visual
      feedback by allowing feedback dot take any position from the 440 pixels along the
      vertical dimension of the screen. This display provided precise information about
      the current level of force relative to the target and to a range of allowable
      force deviation around the target. The other display provided low spatial
      resolution visual feedback by depicting applied force as taking on only three
      discrete values--below, within, or above the target range. Participants produced
      less variable and more complex (higher approximate entropy) force output with the
      displays that had higher spatial resolution. Recurrence quantification analysis
      of the force time series revealed that the display with low visual feedback
      resolution promoted a more intermittent, discontinuous force-production
      performance.

PMID- 20045719
TI  - Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient
      sandy mice: an in vivo microdialysis study.
AB  - Dystrobrevin binding protein-1 gene (DTNBP1), which encodes dysbindin protein,
      has been identified as a schizophrenia susceptibility gene. Dysbindin has been
      shown to contribute to the regulation of exocytosis and formation of synaptic
      vesicles. Although hypofrontality in schizophrenia underlies its pathophysiology,
      the molecular function of dysbindin in synaptic neurotransmission remains
      unclear. In the present study, we investigated depolarization-evoked dopamine
      (DA) and serotonin (5-HT) release in the prefrontal cortex (PFC) of sandy (sdy)
      mice, which have a deletion mutation in the gene encoding DTNBP1. In vivo
      microdialysis analysis revealed that extracellular DA levels in the PFC of wild
      type mice were increased by 60mM KCl stimulation, and the KCl-evoked DA release
      was significantly decreased in sdy mice compared with wild-type mice.
      Extracellular 5-HT levels in the PFC of wild-type mice were also increased by
      60mM KCl stimulation. The KCl-evoked 5-HT release did not differ between wild
      type and sdy mice. There was no difference in basal levels of DA and 5-HT before
      the stimulation between two groups. Behavioral sensitization after repeated
      methamphetamine (METH) treatment was significantly reduced in sdy mice compared
      with wild-type mice whereas no difference was observed in METH-induced
      hyperlocomotion between two groups. These results suggest that dysbindin may have
      a role in the regulation of depolarization-evoked DA release in the PFC and in
      the development of behavioral sensitization induced by repeated METH treatment.

PMID- 20045720
TI  - Involvement of mitochondria on neuroprotective effect of sphingosine-1-phosphate
      in cell death in an in vitro model of brain ischemia.
AB  - Sphingosine-1-phosphate (S1P) has been demonstrated to be an important regulator
      of cell death and survival. Although it has been suggested that the sphingolipid
      may act as a neuroprotector in the cell apoptosis induced by traumatic brain
      injury, the mechanisms involved in this action are unknown. In this study, the
      relationship between S1P and neuroprotective effect was studied in an in vitro
      model of ischemia, maintaining SH-SY5Y human neuroblastoma cells under oxygen
      glucose deprivation (OGD). When cells were treated with 1 microM S1P
      simultaneously with OGD and recovery, cell viability increases in a dose-response
      manner. S1P treatment reduces significantly both necrosis and apoptosis cell
      death. On the other hand, the treatment with specific PKC epsilon (V1-2),
      prevents S1P protective effect of OGD/recovery-induced necrosis. Moreover, S1P
      treatment provokes the translocation of PKC epsilon to the mitochondria. From
      these results, it is reasonable to assume that S1P protection from necrosis is
      mediated by PKC epsilon. We also studied the action of S1P on mitochondrial inner
      membrane potential and mitochondrial Ca(2+) levels during ischemia. In this
      regard, we must point out that S1P treatment reduces the OGD-induced membrane
      depolarization and also reduces the increase of Ca(2+) in mitochondria during
      OGD. Results also indicate that mitochondria from OGD treated cells have
      significantly less ability to resist swelling on Ca(2+) loading than those
      obtained in presence of oxygen and glucose. Nevertheless, when S1P was added,
      this resistance increases considerably. These findings suggest that S1P may have
      a potential role as a neuroprotective agent in brain injury.

PMID- 20045721
TI  - Tanshinone IIA inhibits constitutive STAT3 activation, suppresses proliferation,
      and induces apoptosis in rat C6 glioma cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) is usually
      constitutively activated in a variety of malignancies. Thus, STAT3 may be a
      promising target for treatment of tumor cells. Recently, Tanshinone IIA (Tan
      IIA), a major active constituent from the root of Salvia miltiorrhiza Bunge, was
      reported to have apoptosis inducing effects on a large variety of cancer cells.
      In this study, we evaluate the anti-proliferation and apoptosis inducing effects
      of Tan IIA on C6 glioma cells. Cell growth and proliferation were measured by MTT
      assay, cell apoptosis was observed by flow cytometry and DNA-fragmentation
      analysis. Further more, we investigated inhibitory effects of Tan IIA on STAT3
      activity and its downstream targets: Bcl-XL, cyclin D1. Alteration of STAT3
      activity was examined by measuring their DNA binding activity and tyrosine
      phosphorylation. Changes in the expression levels of Bcl-XL and cyclin D1 were
      examined by Western blot analysis. We found that the cellular growth were
      inhibited and cell apoptosis were observed after the treatment with Tan IIA. The
      STAT3 activity was significantly reduced by Tan IIA parallel with a significant
      attenuation of expression of Bcl-XL and cyclin D1. These results suggest that Tan
      IIA may serve as an effective adjunctive reagent in the treatment of glioma for
      its targeting of constitutive STAT3 signaling.

PMID- 20045722
TI  - In vitro and in vivo anti-inflammatory effects of ethanol extract from Acer
      tegmentosum.
AB  - AIM OF STUDY: Acer tegmentosum has been traditionally used for folk medicine to
      treat hepatic disorders such as hepatitis, hepatic cancer, and hepatic cirrhosis.
      In this study, we demonstrate the ethno-pharmacological activity of Acer
      tegmentosum in in vitro and in vivo inflammatory conditions. RESULTS: The 70%
      ethanol extract (At-EE) of Acer tegmentosum dose-dependently diminished the
      production of nitric oxide (NO), tumour necrosis factor (TNF)-alpha, and
      prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and
      peritoneal macrophages, by a transcriptional mechanism. At-EE also suppressed the
      activation of nuclear factor (NF)-kappaB, activator protein (AP)-1, and cAMP
      responsive element binding (CREB), and simultaneously blocked their upstream
      inflammatory signalling cascades, including Akt, p38, and JNK. Furthermore, At-EE
      protected against LPS-induced cell death induced by reactive oxygen species (ROS)
      and reactive nitrogen species (RNS) and neutralized reactive species generation.
      In agreement with the in vitro results, orally administered At-EE strongly
      ameliorated ear oedema formation induced by arachidonic acid. CONCLUSION: At-EE
      displays strong anti-inflammatory activities in vitro and in vivo, contributing
      to its major ethno-pharmacological role such as anti-hepatitis remedy and may be
      applicable to novel anti-inflammatory therapeutics.

PMID- 20045725
TI  - Jacques Monod, 1910-1976: his life, his work and his commitments.
AB  - Even today, the concepts developed by Jacques Monod during the course of his
      career remain at the core of modern biology. Looking back, Jacques Monod stands
      out as one of the giants who most strongly marked twentieth century science. He
      was endowed with intelligence, rigor, creativity, a relentless sense of deductive
      reasoning and a love of scientific elegance. His name will remain intimately
      associated with the birth, development and triumph of molecular biology. He was
      not only a brilliant scientist, but along with that he was a generous laboratory
      director who gave selflessly to his many students and co-workers. Yet in our
      minds, he will also remain a man with a profound moral commitment to any cause
      which he felt just. He was a true humanist.

PMID- 20045724
TI  - A novel giant peroxisomal superoxide dismutase motif-containing protein.
AB  - Oxidative glutamate toxicity in the neuronal cell line HT22 is a model for
      neuronal cell death by oxidative stress. In this model, extracellular glutamate
      blocks cystine uptake via the glutamate/cystine antiporter system x(c)(),
      eventually leading to depletion of the antioxidant glutathione and cell death. We
      used subtractive suppression hybridization and a screening procedure using
      various HT22 sublines to identify transcripts relevantly upregulated in
      resistance to oxidative glutamate toxicity. One of these coded for a novel
      protein of 3440 amino acids comprising a superoxide dismutase (SOD) motif, which
      we named TIGR for "transcript increased in glutamate resistance." TIGR is mainly
      expressed in the nervous system in cortical pyramidal and hippocampal neurons.
      Intracellularly, TIGR colocalizes with catalase, strongly suggesting a
      peroxisomal localization. Overexpression of TIGR but not of a mutant lacking two
      conserved histidine residues in the SOD motif increased SOD activity and
      protected against oxidative stress in mammalian cells, but had no direct SOD
      activity in yeast. We conclude that this novel giant peroxisomal protein is
      implicated in resistance to oxidative stress. Despite the presence of a SOD
      motif, which is necessary for protection in mammalian cells, the protein is not a
      functional SOD, but might be involved in SOD activity.

PMID- 20045726
TI  - Improvement in doxorubicin productivity by overexpression of regulatory genes in
      Streptomyces peucetius.
AB  - Biosynthesis of doxorubicin (DXR) is tightly regulated, limiting its production
      in Streptomyces peucetius cultures. The regulatory genes dnrN, dnrI, afsR, and
      metK1-sp from S. peucetius ATCC 27952 were cloned into the pIBR25 expression
      vector under the control of the strong ermE* promoter to enhance DXR production.
      The constructed expression plasmids, pNI25 (with dnrN-dnrI), pNIS25 (with dnrN
      dnrI-metK1-sp), pNIR25 (with dnrN-dnrI-afsR), pRS25 (with afsR-metK1-sp) and
      pNIRS25 (with dnrN-dnrI-afsR-metK1-sp), were transformed into S. peucetius. The
      recombinant strains NI, NIS and NIR produced greater amounts of DXR than the
      parental strain with an increment of 1.2-fold by pNI25, 1.4-fold by pNIS25 and
      4.3-fold by pNIR25, whereas pRS25 and pNIRS25 had no significant effect on DXR
      production. We also studied the transcriptional level of overexpressed regulatory
      genes and relative production of DXR, daunorubicin (DNR) and epsilon
      rhodomycinone (RHO) in each recombinant strain.

PMID- 20045727
TI  - Sex steroids as inflammatory regulators.
AB  - It is becoming increasingly clear that endogenous sex steroids are key players in
      a range of inflammatory contexts. Androgens and estrogens have been shown to have
      a profound influence on the function of inflammatory cells including macrophages
      and on the secretion and activation of a range of plasma-borne inflammatory
      mediators. The menopause and polymorphisms in estrogen receptor genes have
      separately been shown to affect the incidence of a range of inflammatory
      disorders. Sex steroids themselves have been shown to be protective in certain
      conditions; harmful in others. This review will summarize their documented
      effects on inflammatory processes, with particular focus on two areas that have
      received much recent attention: the antiatherosclerotic properties of estrogens
      in females and the wound healing effects of sex steroids.

PMID- 20045728
TI  - Unique features of breast cancer in Asian women--breast cancer in Taiwan as an
      example.
AB  - Breast carcinoma is one of the most common cancers in women and is known to arise
      from a multifactorial process, the effect of reproductive risk factors strongly
      supporting a hormonal role in its etiology. Breast cancer in Asia is
      characterized by a lower incidence than in Western populations, but is still the
      leading type of cancer in Asian women, and a significant increasing tread
      indicates that it is an issue of particular public health importance. Asian
      breast cancer is characterized by early tumor onset, showing a relatively younger
      median age at diagnosis. Recently, scientists began to explore the tumorigenic
      mechanisms underlying breast cancer formation at the molecular level. Both a
      candidate-gene approach and genome-wide association studies have yielded crucial
      insights into breast cancer susceptibility genes initiating breast tumorigenesis.
      As expected, ethnic/racial variation in the genotypic frequency of these genes
      results in differences in breast cancer incidence in different populations.
      Furthermore, the question of how important these genes are in Asian breast cancer
      remains to be explored. It has been demonstrated that gene expression profiles
      and gene sets are prognostic and predictive for patients with breast cancer.
      Originally, due to its early onset, it was speculated that Asian breast cancer
      would have a higher frequency of the basal-like subtype of breast cancer, a
      molecular subtype characterized by poor differentiation, resulting in a
      relatively poor progression; however, recent findings do not support this
      speculation. The frequency of the luminal-A subtype of breast cancer,
      characterized by estrogen receptor expression, is similar to that in breast
      cancer in Caucasian, supporting the usefulness of hormone-based therapy in Asian
      breast cancer.

PMID- 20045723
TI  - Reactive oxygen species, cellular redox systems, and apoptosis.
AB  - Reactive oxygen species (ROS) are products of normal metabolism and xenobiotic
      exposure, and depending on their concentration, ROS can be beneficial or harmful
      to cells and tissues. At physiological low levels, ROS function as "redox
      messengers" in intracellular signaling and regulation, whereas excess ROS induce
      oxidative modification of cellular macromolecules, inhibit protein function, and
      promote cell death. Additionally, various redox systems, such as the glutathione,
      thioredoxin, and pyridine nucleotide redox couples, participate in cell signaling
      and modulation of cell function, including apoptotic cell death. Cell apoptosis
      is initiated by extracellular and intracellular signals via two main pathways,
      the death receptor- and the mitochondria-mediated pathways. Various pathologies
      can result from oxidative stress-induced apoptotic signaling that is consequent
      to ROS increases and/or antioxidant decreases, disruption of intracellular redox
      homeostasis, and irreversible oxidative modifications of lipid, protein, or DNA.
      In this review, we focus on several key aspects of ROS and redox mechanisms in
      apoptotic signaling and highlight the gaps in knowledge and potential avenues for
      further investigation. A full understanding of the redox control of apoptotic
      initiation and execution could underpin the development of therapeutic
      interventions targeted at oxidative stress-associated disorders.

PMID- 20045729
TI  - Alteration of cardiac cytochrome P450-mediated arachidonic acid metabolism in
      response to lipopolysaccharide-induced acute systemic inflammation.
AB  - Cytochrome P450 (CYP) generated cardioprotective metabolites, epoxyeicosatrienoic
      acids (EETs), and cardiotoxic metabolites, hydroxyeicosatetraenoic acids (HETEs)
      levels are determined by many factors, including the induction or repression of
      the CYP enzymes, responsible for their formation. Therefore, we examined the
      effect of acute inflammation on the expression of CYP epoxygenases and CYP omega
      hydroxylases in the heart, kidney, and liver and the cardiac CYP-mediated
      arachidonic acid metabolism. For this purpose, male Sprague-Dawley rats were
      injected intraperitoneally with LPS (1mg/kg). After 6, 12, or 24h, the tissues
      were harvested and the expression of CYP genes and protein levels were determined
      using real time-PCR, and Western blot analyses, respectively. Arachidonic acid
      metabolites formations were determined by liquid chromatography-electron spray
      ionization-mass spectrometry LC-ESI-MS. Our results showed that inflammation
      significantly decreased the CYP epoxygenases expression in the heart, kidney and
      liver with a concomitant decrease in the EETs produced by these enzymes. In
      contrast to CYP expoxygenses, inflammation differentially altered CYP omega
      hydroxylases expression with a significant increase in 20-HETE formation. The
      present study demonstrates for the first time that acute inflammation decreases
      CYP epoxygenases and their associated cardioprotective metabolites, EETs while on
      the other hand increases CYP omega-hydroxylases and their associated cardiotoxic
      metabolites, 20-HETE. These changes may be involved in the development and/or
      progression of cardiovascular diseases by inflammation.

PMID- 20045730
TI  - Effects of Kir2.1 gene transfection in cochlear hair cells and application of
      neurotrophic factors on survival and neurite growth of co-cultured cochlear
      spiral ganglion neurons.
AB  - Immature inner hair cells (IHCs) produce spontaneous action potentials, which may
      be associated with the survival of spiral ganglion neurons (SGNs) during early
      development. Later, this activity ceases in part by the expression of Kir
      channels. In the present study, SGNs were co-cultured with organ of Corti in
      which a Kir2.1 channel was over-expressed in an attempt to block the spontaneous
      activity of IHCs. The over-expression led to a reduced survival and neurite
      growth accompanied by increased SGN apoptosis. The enhanced activation of
      apoptosis was consistent with the inhibition of the survival-promoting pathway
      and the disruption of [Ca(2+)](i) homeostasis. Furthermore, the effect of Kir2.1
      over-expression can be reversed by exogenous neurotrophic factors (NTFs). These
      results are consistent with the hypothesis that the earlier-than-normal
      expression of Kir2.1 in HCs inhibits their spontaneous activity required for SGN
      survival and neurite growth.

PMID- 20045731
TI  - Transgenic mouse models of mitochondrial toxicity associated with HIV/AIDS and
      antiretrovirals.
AB  - Since the discovery of HIV-1 and the explosion of interest in antiretroviral
      therapy, there has been an increasing demand for animal models to determine the
      underlying mechanisms of HIV/AIDS disease progression. Additionally, the advent
      of nucleoside reverse transcriptase inhibitors (NRTI) and the associated side
      effects necessitated an approach to explore NRTI toxic mechanisms in vivo.
      Determining the pathophysiological effects of antiretroviral drugs (such as
      NRTIs) on animals became an important part of understanding the risks associated
      with current therapeutic approaches where mitochondrial toxicity is important.
      Transgenic mouse models (TG) in HIV/AIDS research are valuable tools to
      investigate the pathophysiology of HIV-1 infection and the effects of the
      antiretrovirals used to treat the infection. TGs enable investigators to control
      these variables experimentally. This chapter summarizes data from TG models that
      help unravel the individual and combined effects of HIV-1 infection and NRTI
      therapy on mouse physiology. Emphasis is placed on cardiac mitochondrial toxicity
      of NRTIs used in HIV/AIDS.

PMID- 20045732
TI  - The use of antisense oligonucleotides in Xenopus oocytes.
AB  - The ability to manipulate gene expression in Xenopus oocytes and then generate
      fertilized embryos by transfer into host females has made it possible to rapidly
      characterize maternal signaling pathways in vertebrate development. Maternal
      mRNAs in particular can be efficiently depleted using antisense
      deoxyoligonucleotides (oligos), mediated by endogenous RNase-H activity. Since
      the microinjection of antisense reagents or mRNAs into eggs after fertilization
      often fails to affect maternal signaling pathways, mRNA depletion in the Xenopus
      oocyte is uniquely suited to assessing maternal functions. In this review, we
      highlight the advantages of using antisense in Xenopus oocytes and describe basic
      methods for designing and choosing effective oligos. We also summarize the
      procedures for fertilizing cultured oocytes by host-transfer and interpreting the
      specificity of antisense effects. Although these methods can be technically
      demanding, the use of antisense in oocytes can be used to address biological
      questions that are intractable in other experimental settings.

PMID- 20045733
TI  - Extracellular production of riboflavin-binding protein, a potential bitter
      inhibitor, by Brevibacillus choshinensis.
AB  - Riboflavin-binding protein (RBP) is a glycophosphoprotein found in hen eggs. We
      previously identified the extraordinary characteristic of RBP in reducing
      bitterness. For a more detailed study on the mode of action and industrial
      application of this characteristic, we investigated the microbial production of
      recombinant RBP (rRBP). We constructed a chicken RBP gene expression vector by
      inserting the RBP cDNA in pNCMO2, the Escherichia coli-Brevibacillus choshinensis
      shuttle vector. B. choshinensis HPD31 transformants produced 0.8g/l of processed
      and unglycosylated RBP in a soluble form in the culture supernatant. However, the
      expressed RBP was partially dimerized and monomeric RBP was purified by two step
      anion-exchange and gel-filtration chromatographies. The purified rRBP elicited
      bitterness reduction against quinine and caffeine, although it largely lost its
      riboflavin-binding ability. These results indicated that glycosylation and
      riboflavin-binding ability are not essential for the bitterness reduction of RBP.
      In addition, we assessed the usefulness of the Brevibacillus system for the
      expression and secretion of RBP as a new type of bitterness inhibitor.

PMID- 20045734
TI  - Recombinant derivatives of botulinum neurotoxin A engineered for trafficking
      studies and neuronal delivery.
AB  - Work from multiple laboratories has clarified how the structural domains of
      botulinum neurotoxin A (BoNT/A) disable neuronal exocytosis, but important
      questions remain unanswered. Because BoNT/A intoxication disables its own uptake,
      light chain (LC) does not accumulate in neurons at detectable levels. We have
      therefore designed, expressed and purified a series of BoNT/A atoxic derivatives
      (ad) that retain the wild type features required for native trafficking.
      BoNT/A1ad(ek) and BoNT/A1ad(tev) are full length derivatives rendered atoxic
      through double point mutations in the LC protease (E(224)>A; Y(366)>A). DeltaLC
      peptide-BoNT/A(tev) and DeltaLC-GFP-BoNT/A(tev) are derivatives wherein the
      catalytic portion of the LC is replaced with a short peptide or with GFP plus the
      peptide. In all four derivatives, we have fused the S6 peptide sequence
      GDSLSWLLRLLN to the N-terminus of the proteins to enable site-specific attachment
      of cargo using Sfp phosphopantetheinyl transferase. Cargo can be attached in a
      manner that provides a homogeneous derivative population rather than a
      polydisperse mixture of singly and multiply-labeled molecular species. All four
      derivatives contain an introduced cleavage site for conversion into disulfide
      bonded heterodimers. These constructs were expressed in a baculovirus system and
      the proteins were secreted into culture medium and purified to homogeneity in
      yields ranging from 1 to 30 mg per liter. These derivatives provide unique tools
      to study toxin trafficking in vivo, and to assess how the structure of cargo
      linked to the heavy chain (HC) influences delivery to the neuronal cytosol.
      Moreover, they create the potential to engineer BoNT-based molecular vehicles
      that can target therapeutic agents to the neuronal cytoplasm.

PMID- 20045735
TI  - Effect of probiotic Pediococcus acidilactici on antioxidant defences and
      oxidative stress of Litopenaeus stylirostris under Vibrio nigripulchritudo
      challenge.
AB  - Antioxidant defences and induced oxidative stress tissue damage of the blue
      shrimp Litopenaeus stylirostris, under challenge with Vibrio nigripulchritudo,
      were investigated for a 72-h period. For this purpose, L. stylirostris were first
      infected by immersion with pathogenic V. nigripulchritudo strain SFn1 and then
      antioxidant defences: superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (Gpx), Total antioxidant status (TAS), glutathiones and induced tissue
      damage (MDA and carbonyl proteins) were determined in the digestive gland at 0,
      12, 24, 48 and 72 h post-infection (h.p.i.). In the meantime, TAS was also
      measured in the blood. Infection level of the shrimps during the challenge was
      followed by determining V. nigripulchritudo prevalence and load in the haemolymph
      of the shrimps. Changes in all these parameters during the 72-h.p.i. period were
      recorded for control shrimps and shrimps previously fed for one month with
      probiotic Pediococcus acidilactici MA18/5M at 10(7) CFU g(-1) of feed. Our
      results showed that immersion with V. nigripulchritudo led to maximal infection
      level in the haemolymph at 24 h.p.i. preceding the mortality peak recorded at 48
      h.p.i. Significant decreases in the antioxidant defences were detected from 24
      h.p.i. and beyond that time infection leaded to increases in oxidative stress
      level and tissue damage. Compared to control group, shrimps fed the probiotic
      diet showed lower infection (20% instead of 45% at 24 h.p.i. in the control
      group) and mortality (25% instead of 41.7% in the control group) levels.
      Moreover, infected shrimp fed the probiotic compared to uninfected control
      shrimps exhibited very similar antioxidant status and oxidative stress level.
      Compared to the infected control group, shrimps fed the probiotic sustained
      higher antioxidant defences and lower oxidative stress level. This study shows
      that bacterial infection leads to oxidative stress in L. stylirostris and
      highlighted a beneficial effect of P. acidilactici, suggesting both a competitive
      exclusion effect leading to a reduction of the infection level and/or an
      enhancement of the antioxidant status of the shrimps.

PMID- 20045736
TI  - Unattended emotional faces elicit early lateralized amygdala-frontal and fusiform
      activations.
AB  - Human adaptive behaviour to potential threats involves specialized brain
      responses allowing rapid and reflexive processing of the sensory input and a more
      directed processing for later evaluation of the nature of the threat. The
      amygdalae are known to play a key role in emotion processing. It is suggested
      that the amygdalae process threat-related information through a fast subcortical
      route and slower cortical feedback. Evidence from human data supporting this
      hypothesis is lacking. The present study investigated event-related neural
      responses during processing of facial emotions in the unattended hemifield using
      magnetoencephalography (MEG) and found activations of the amygdala and anterior
      cingulate cortex to fear as early as 100 ms. The right amygdala exhibited
      temporally dissociated activations to input from different visual fields,
      suggesting early subcortical versus later cortical processing of fear. We also
      observed asymmetrical fusiform activity related to lateralized feed-forward
      processing of the faces in the visual-ventral stream. Results demonstrate fast,
      automatic, and parallel processing of unattended emotional faces, providing
      important insights into the specific and dissociated neural pathways in emotion
      and face perception.

PMID- 20045737
TI  - Molecular phylogenetics supports multiple evolutionary transitions from marine to
      freshwater habitats in ariid catfishes.
AB  - Transitions between the marine and freshwater environments represent an
      extraordinary ecological shift that has promoted diversification in many groups
      of aquatic organisms. Here, molecular phylogenetics is utilized to investigate
      habitat transitions in a group of catfishes (Ariidae) that includes species
      inhabiting marine and brackish waters (>110 species) as well as freshwater
      environments (approximately 40 species). The Ariidae is nested within the
      Otophysi, the largest clade of primary freshwater fishes with four orders and 67
      families. Optimizations of habitat transitions (freshwater vs. marine) onto a
      previously inferred phylogeny suggest a single invasion of marine waters at the
      root of the ariid tree followed by 10-15 events of freshwater colonization,
      implying reversion to the primitive otophysan condition. Thus, ariids provide an
      extraordinary example of bidirectional habitat transitions in fishes. Freshwater
      recolonization has occurred in all major provinces where ariids are present, such
      as the New World (Mesoamerica and South America), Madagascar, Africa, Southeast
      Asia, and the Sahul continent (Australia and New Guinea). The remarkable
      diversity of freshwater ariids in Australia-New Guinea and Mesoamerica is
      presumed to have been facilitated by the originally depauperate freshwater
      ichthyofaunas in both regions, particularly the low diversity of primary
      otophysan families in Mesoamerica and their absence in Australia and New Guinea.
      The lack of phylogenetic resolution among basal Sahul lineages coupled with their
      extraordinary level of morphological divergence and trophic diversity suggests an
      ancient rapid radiation promoted by freshwater colonization. For this reason,
      Sahul ariids represent an excellent system for studying diversification
      associated with habitat transitions.

PMID- 20045738
TI  - Front-line high-dose chemotherapy with rituximab showed excellent long-term
      survival in adults with aggressive large b-cell lymphoma: final results of a
      Phase II GOELAMS Study.
AB  - To evaluate the effect of rituximab in poor-prognosis patients with diffuse large
      B-cell lymphoma (DLBCL), a multicenter phase II trial combining rituximab with
      chemotherapy followed by high-dose therapy (HDT) with autologous stem cell
      transplant was conducted by the Groupe Ouest-Est des Leucemies et des Autres
      Maladies du Sang (GOELAMS). Patients were aged 18 to 60 years, with newly
      diagnosed CD20-expressing DLBCL, and at least 2 adverse risk factors as defined
      by the age-adjusted International Prognostic Index (aa-IPI). The treatment
      consisted of 2 courses of high-dose CHOP-like regimen on day 1 and 15 and 1
      course of methotrexate and cytarabine on day 36. Four doses of rituximab (375
      mg/m(2)) were infused on days 1, 15, 22, and 36. For patients who achieved at
      least a partial remission (PR), HDT followed by autologous stem cell transplant
      was performed on day 66. From April 2002 to May 2003, 42 patients were eligible.
      Half were high aa-IPI risk patients. Thirty-eight patients (90%) completed the
      treatment. Treatment-related mortality was 7% and no toxic death was related to
      rituximab. Complete response rate after the end of the full treatment was 67%.
      With a median follow-up of 66 months, event-free survival and overall survival
      rates were 55% and 74%, respectively. Median survival was not reached. First-line
      HDT with rituximab offers promising results for young adults with intermediate
      high or high aa-IPI high-grade lymphoma. Immediate and late toxicities were low.
      This treatment is being randomly compared prospectively with CHOP-14-rituximab in
      young adults with DLBCL (GOELAMS 075 trial).

PMID- 20045739
TI  - PARP is involved in replicative aging in Neurospora crassa.
AB  - Modification of proteins by the addition of poly(ADP-ribose) is carried out by
      poly(ADP-ribose) polymerases (PARPs). PARPs have been implicated in a wide range
      of biological processes in eukaryotes, but no universal function has been
      established. A study of the Aspergillus nidulans PARP ortholog (PrpA) revealed
      that the protein is essential and involved in DNA repair, reminiscent of findings
      using mammalian systems. We found that a Neurospora PARP orthologue (NPO) is
      dispensable for cell survival, DNA repair and epigenetic silencing but that
      replicative aging of mycelia is accelerated in an npo mutant strain. We propose
      that PARPs may control aging as proposed for Sirtuins, which also consume NAD+
      and function either as mono(ADP-ribose) transferases or protein deacetylases.
      PARPs may regulate aging by impacting NAD+/NAM availability, thereby influencing
      Sirtuin activity, or they may function in alternative NAD+-dependent or NAD+
      independent aging pathways.

PMID- 20045740
TI  - Evaluation of the role of nitric oxide in acid sensing ion channel mediated cell
      death.
AB  - Acid sensing ion channels (ASICs) are widely expressed in central and peripheral
      nervous system. They are involved in a variety of physiological and
      pathophysiological processes: synaptic transmission, learning and memory, pain
      perception, ischemia, etc. During ischemia, metabolic acidosis causes the drop of
      extracellular pH (pHe) which in turn activates ASICs. Activation of calcium
      permeable ASIC1a has been implicated in neuronal death. ASICs are modulated by
      several redox reagents, divalent cations and nitric oxide (NO). Although NO
      potentiates ASIC mediated currents, the physiological significance of such
      modulation has not been studied in detail. We have evaluated the role of
      endogenous NO in cell death at different pH, mediated by the activation of ASICs.
      At pH 6.1, death rates of ASIC1 expressing Neuro2A (N2A) cells are significantly
      higher in comparison to the cells that do not express ASICs. Amiloride, a blocker
      of ASICs protects the cell from acid-injury. Sodium nitroprusside, a potent NO
      donor not only increases the ASIC mediated currents but also increases cell death
      at low pH. L-Arg, the precursor of NO also potentiates ASICs in a pH dependent
      manner. L-Arg-induced NO production and potentiation of ASICs were observed at
      pHs 7.4, 7.2, 7.0 and 6.8. Lowering the pH below 6.8 did not result in
      significant production of NO or potentiation of ASICs upon L-Arg stimulation. Our
      results suggest that potentiation of ASICs by NO and subsequent cell death in
      vivo depends on the severity of acidosis. During mild and moderate acidosis, NO
      promotes cell death by potentiating ASICs, whereas this potentiation subsides in
      severe acidosis due to inhibition of NO synthase.

PMID- 20045741
TI  - Low-density lipoprotein and oxysterols suppress the transcription of CTP:
      Phosphoethanolamine cytidylyltransferase in vitro.
AB  - The rate-limiting step in phosphatidylethanolamine (PE) synthesis by the CDP
      ethanolamine pathway is the second step, which is catalyzed by
      CTP:phosphoethanolamine cytidylyltransferase (ET). The rate-limiting step for
      phosphatidylcholine biosynthesis by the CDP-choline pathway is also the second
      step, which is catalyzed by CTP:phosphocholine cytidylyltransferase (CT). The
      transcription of the most active form of CT, CTalpha, in serum-starved cells was
      stimulated by fetal bovine serum (FBS). Therefore, we were interested in the
      effects of FBS on the transcription of ET. Unexpectedly, the ET mRNA levels were
      significantly increased after NIH3T3 cells were cultured in serum-starved medium
      (0.5% FBS) longer than 8h, and the increase was suppressed by the addition of
      FBS. Actinomycin-D inhibited the increased ET mRNA levels in serum-starved cells.
      ET enzyme activities and protein amounts were also increased after serum
      starvation. These results suggest that FBS contains substances that inhibit the
      transcription of ET. To identify these substances, cells were incubated with
      several fractions of FBS separated by molecular sizes. As expected from the
      results, low-density lipoprotein, 25-hydroxycholesterol (25-OHC), 24-OHC, 27-OHC,
      24(S),25-epoxycholesterol and mevalonolactate suppressed the ET mRNA levels in
      serum-starved cells, similar to 3-hydroxy-3-methylglutaryl-CoA reductase but not
      CTalpha. These results suggest that oxysterols are important regulating lipids
      for the suppression of ET transcription and may help maintain the contents of PE
      and cholesterol at the same ratio in the cellular membrane.

PMID- 20045743
TI  - Obesity as a clinical and public health problem: is there a need for a new
      definition based on lipotoxicity effects?
AB  - The risk functions for obesity (defined as the quantitative relation between
      degree of obesity throughout its range and the risk of health problems) have been
      used to define 'obesity' as an excess storage of fat in the body to such an
      extent that it causes health problems leading to increased mortality. The
      lipotoxicity theory implies that the fat stored in droplets of triglycerides in
      the cells are biologically inert and that the metabolic dysfunctions are
      primarily due to the increased exposure of the cells to fatty acids. If this is
      true, it has profound implications for the interpretations of the multiple
      epidemiological studies of the risk functions. It is obvious from all these
      studies that the sizes of the fat depots are risk indicators of health effects in
      various ways. Paradoxically, the sizes of the fat stores are also indicators of
      the preceding implementation of the ability of the body to protect itself against
      the toxic effects of the free fatty acids. The current risk of metabolic
      dysfunctions appears to be determined by the balance between the rate of loading
      of the body with fatty acids and the rate of eliminating the fatty acids by
      either triglyceride storage or oxidation. The progress in the development of the
      dysfunction then depends on the persistence of the imbalance leading to future
      cumulative exposure of the cells to the toxic effects of the fatty acids rather
      than on the current size of the fat depots. This may be considered as a reason
      for changing the definition of obesity to one based on better estimates of future
      risks of health problems derived from later metabolic dysfunctions rather than on
      the past coping with the exposure to the fatty acids by storage as triglycerides.
      Implementation of such definition would require a test that measures this
      residual capacity to avoid excess exposure of the cells to the fatty acids before
      the metabolic dysfunctions have emerged. In analogy with the glucose tolerance
      test, a fatty acid tolerance test may be needed to identify individuals who are
      at a level of risk for developing lipotoxicity induced metabolic dysfunctions
      such that they require intervention. This test would ideally be a single
      biomarker that would determine residual capacity for adipose expansion, fatty
      acid oxidation and safe ectopic lipid deposition.

PMID- 20045742
TI  - Regulatory role for phosphatidylcholine transfer protein/StarD2 in the metabolic
      response to peroxisome proliferator activated receptor alpha (PPARalpha).
AB  - Phosphatidylcholine transfer protein (PC-TP, a.k.a. StarD2) is abundantly
      expressed in liver and is regulated by PPARalpha. When fed the synthetic
      PPARalpha ligand fenofibrate, Pctp(-/-) mice exhibited altered lipid and glucose
      metabolism. Microarray profiling of livers from fenofibrate fed wild type and
      Pctp(-/-) mice revealed differential expression of a broad array of metabolic
      genes, as well as their regulatory transcription factors. PC-TP expression in
      cell culture controlled the activities of both PPARalpha and HNF4alpha,
      suggesting that the mechanism by which it modulates hepatic metabolism is at
      least in part via activation of transcription factors that govern nutrient
      homeostasis.

PMID- 20045744
TI  - Reaction mechanism of 5,8-linoleate diol synthase, 10R-dioxygenase, and 8,11
      hydroperoxide isomerase of Aspergillus clavatus.
AB  - Aspergilli express fusion proteins of an animal haem peroxidase domain with fatty
      acid dioxygenase (DOX) activity ( approximately 600 amino acids) and a functional
      or non-functional hydroperoxide isomerase/cytochrome P450 domain ( approximately
      500 amino acids with EXXR and GPHXCLG motifs). 5,8-Linoleate diol synthases (LDS;
      ppoA) and 10R-DOX (ppoC) of Aspergillusnidulans and A. fumigatus belong to this
      group. Our objective was to determine the oxylipins formed from linoleic acid by
      A. clavatus and their mechanism of biosynthesis. A. clavatus oxidized linoleic
      acid to (8R)-hydroperoxylinoleic acid (8R-HPODE), (10R)-hydroperoxy-8(E),12(Z)
      octadecadienoic acid (10R-HPODE), and to (5S,8R)-dihydroxy- and (8R,11S)
      dihydroxylinoleic acids (DiHODE) as major products. This occurred by abstraction
      of the pro-S hydrogen at C-8 and antarafacial dioxygenation at C-8 or at C-10
      with double bond migration. 8R-HPODE was then isomerized to 5S,8R-DiHODE and to
      8R,11S-DiHODE by abstraction of the pro-S hydrogens at C-5 and C-11 of 8R-HPODE,
      respectively, followed by suprafacial oxygenation. The genome of A. clavatus
      codes for two enzymes, which can be aligned with >65% amino acid identity to 10R
      DOX and 5,8-LDS, respectively. The 5,8-LDS homologue likely forms and isomerizes
      8R-HPODE to 5S,8R-DiHODE. A third gene (ppoB) codes for a protein which carries a
      serine residue at the cysteine position of the P450 motif. This Cys to Ser
      replacement is known to abolish P450 2B4 catalysis and the hydroperoxide
      isomerase activity of 5,8-LDS, suggesting that ppoB of A. clavatus may not be
      involved in the biosynthesis of 8R,11S-DiHODE.

PMID- 20045746
TI  - Systems Approach to daily clinical care.
AB  - Safety and quality of healthcare provision are affected by a number of factors.
      These factors include the clinical skills of the treating surgeon or other
      physician, but also the way practitioners think and behave as members of a
      healthcare team, and the clinical environment in which care is provided. We first
      discuss Bahal et al.'s paper as a demonstration of the Systems Approach to
      clinical performance and patient safety. We then highlight recent advances driven
      by the Systems Approach in understanding and measuring clinical decision-making,
      teamworking, and the clinical environment. We conclude that human factors
      research can provide an understanding of how to balance conflicting opinions and
      priorities in clinical care with the best interests of the patient, in a manner
      which allows each doctor to fulfil their duty of care.

PMID- 20045745
TI  - Functional biomimetic analogs help remineralize apatite-depleted demineralized
      resin-infiltrated dentin via a bottom-up approach.
AB  - Natural biominerals are formed through metastable amorphous precursor phases via
      a bottom-up, nanoparticle-mediated mineralization mechanism. Using an acid-etched
      human dentin model to create a layer of completely demineralized collagen matrix,
      a bio-inspired mineralization scheme has been developed based on the use of dual
      biomimetic analogs. These analogs help to sequester fluidic amorphous calcium
      phosphate nanoprecursors and function as templates for guiding homogeneous
      apatite nucleation within the collagen fibrils. By adopting this scheme for
      remineralizing adhesive resin-bonded, completely demineralized dentin, we have
      been able to redeposit intrafibrillar and extrafibrillar apatites in completely
      demineralized collagen matrices that are imperfectly infiltrated by resins. This
      study utilizes a spectrum of completely and partially demineralized dentin
      collagen matrices to further validate the necessity for using a biomimetic analog
      containing medium for remineralizing resin-infiltrated partially demineralized
      collagen matrices in which remnant seed crystallites are present. In control
      specimens in which biomimetic analogs are absent from the remineralization
      medium, remineralization could only be seen in partially demineralized collagen
      matrices, probably by epitaxial growth via a top-down crystallization approach.
      Conversely, in the presence of biomimetic analogs in the remineralization medium,
      intrafibrillar remineralization of completely demineralized collagen matrices via
      a bottom-up crystallization mechanism can additionally be identified. The latter
      is characterized by the transition of intrafibrillar minerals from an inchoate
      state of continuously braided microfibrillar electron-dense amorphous strands to
      discrete nanocrystals, and ultimately into larger crystalline platelets within
      the collagen fibrils. Biomimetic remineralization via dual biomimetic analogs has
      the potential to be translated into a functional delivery system for salvaging
      failing resin-dentin bonds.

PMID- 20045747
TI  - Surgical management of neurocysticercosis.
AB  - Neurocysticercosis (NCC) is caused by the larval form of the pork tapeworm Taenia
      solium and is the commonest parasitic infestation of the central nervous system.
      NCC is usually managed medically but in some instances surgery is required.
      Magnetic resonance imaging (MRI) and computed tomography (CT) are often able to
      provide the diagnosis of NCC in most patients with intraventricular and
      parenchymal cysts but in patients with hydrocephalus without any cysts, the
      diagnosis is confirmed by the presence of cysticercal antibodies in the serum.
      Surgery is usually recommended for intraventricular cysts, hydrocephalus, large
      cisternal cysts, large parenchymal cysts and when the diagnosis is not certain on
      imaging studies. For intraventricular cysts, endoscopic surgery is the procedure
      of choice as it is minimally invasive. For incompletely excised cysts and cysts
      or granulomas in locations such as the spinal cord, medical treatment with
      steroids and albendazole is recommended. Hydrocephalus is treated with a
      ventriculo-peritoneal shunt but shunts in these patients suffer from frequent
      obstructions and require multiple revisions. The outcome for patients with
      intraventricular and parenchymal cysts is usually good but for those with
      hydrocephalus associated with cisternal or racemose cysts and with cysticercotic
      meningitis, the mortality is high.

PMID- 20045748
TI  - 22q11.2 microduplication in two patients with bladder exstrophy and hearing
      impairment.
AB  - Bladder exstrophy is a congenital malformation of the bladder and urethra. The
      genetic basis of this malformation is unknown however it is well known that
      chromosomal aberrations can lead to defects in organ development. A few bladder
      exstrophy patients have been described to carry chromosomal aberrations.
      Chromosomal rearrangements of 22q11.2 are implicated in several genomic disorders
      i.e. DiGeorge/velocardiofacial- and cat-eye syndrome. Deletions within this
      chromosomal region are relatively common while duplications of 22q11.2 are much
      less frequently observed. An increasing number of reports of microduplications of
      this region describe a highly variable phenotype. We have performed array-CGH
      analysis of 36 Swedish bladder exstrophy patients. The analysis revealed a
      similar and approximately 3 Mb duplication, consistent with the recently
      described 22q11.2 microduplication syndrome, in two unrelated cases with bladder
      exstrophy and hearing impairment. This finding was confirmed by multiplex
      ligation-dependent probe amplification (MLPA) and FISH analysis. Subsequent MLPA
      analysis of this chromosomal region in 33 bladder exstrophy patients did not
      reveal any deletion/duplication within this region. MLPA analysis of 171
      anonymous control individuals revealed one individual carrying this
      microduplication. This is the first report of 22q11.2 microduplication associated
      with bladder exstrophy and hearing impairment. Furthermore the finding of one
      carrier among a cohort of normal controls further highlights the variable
      phenotype linked to this microduplication syndrome.

PMID- 20045750
TI  - Fractional order phase shaper design with Bode's integral for iso-damped control
      system.
AB  - The phase curve of an open loop system is flat in nature if the derivative of its
      phase with respect to frequency is zero. With a flat-phase curve, the
      corresponding closed loop system exhibits an iso-damped property i.e. maintains
      constant overshoot with the change of gain. This implies enhanced parametric
      robustness e.g. to variation in system gain. In the recent past, fractional order
      (FO) phase shapers have been proposed by contemporary researchers to achieve
      enhanced parametric robustness. In this paper, a simple methodology is proposed
      to design an appropriate FO phase shaper to achieve phase flattening in a control
      loop, comprising a plant controlled by a classical Proportional Integral
      Derivative (PID) controller. The methodology is demonstrated with MATLAB
      simulation of representative plants and accompanying PID controllers.

PMID- 20045751
TI  - Learning to imitate stochastic time series in a compositional way by chaos.
AB  - This study shows that a mixture of RNN experts model can acquire the ability to
      generate sequences that are combination of multiple primitive patterns by means
      of self-organizing chaos. By training the model, each expert learns a primitive
      sequence pattern, and a gating network learns to imitate stochastic switching of
      the multiple primitives via chaotic dynamics, utilizing a sensitive dependence on
      initial conditions. As a demonstration, we present a numerical simulation in
      which the model learns Markov chain switching among some Lissajous curves by
      chaotic dynamics. Our analysis shows that by using a sufficient amount of
      training data, balanced with the network memory capacity, it is possible to
      satisfy the conditions for embedding the target stochastic sequences into a
      chaotic dynamical system. It is also shown that reconstruction of a stochastic
      time series by a chaotic model can be stabilized by adding a negligible amount of
      noise to the dynamics of the model.

PMID- 20045752
TI  - Is it possible to use a single ancillary trocar to finish laparoscopic
      cystectomy?

PMID- 20045753
TI  - Laparoscopic myomectomy.
AB  - Since the initial description of laparoscopic myomectomy (LM) in 1979, many
      reports of this technique have been published worldwide. The indications for LM
      have grown in line with improvements in laparoscopic techniques and instruments
      over the last decade. LM offers several benefits to patients but remains a
      challenging technical procedure that is associated with high surgical morbidity
      and a high incidence of blood transfusion. LM procedures include excision of the
      myoma(s), repair of myometrium, and removal of the myoma from the abdomen. The
      control of operative blood loss is crucial, especially in the case of large
      intramural fibroids. Different studies have found wide variations in the
      incidence of recurrence after LM. Ultrasound imaging and Doppler velocimetry can
      be used to assess uterine scars after LM. Uterine rupture during pregnancy is a
      serious concern after LM, and all published cases report the occurrence of
      rupture before the start of labor. Surgical strategies are needed to overcome
      these problems associated with LM. Although LM is minimally invasive in terms of
      the wound, it remains an advanced and invasive procedure. An appropriate
      management strategy is required for each patient, and careful discussion and
      counseling regarding all the issues are necessary.

PMID- 20045754
TI  - Prenatal sonographic features of fetuses in trisomy 13 pregnancies (III).
AB  - Prenatal ultrasound is a powerful tool for the detection of structural
      abnormalities of fetuses in trisomy 13 pregnancies. This article provides a
      comprehensive review of the prenatal sonographic features of trisomy 13 fetuses
      in the second and third trimesters, including cystic hygroma and nuchal edema,
      congenital heart defects, hydrops fetalis, omphalocele, diaphragmatic hernia,
      urinary tract abnormalities, and abnormal extremities and polydactyly.

PMID- 20045755
TI  - Effect of estrogen on the activity and growth of human osteoclasts in vitro.
AB  - OBJECTIVE: Estrogen deficiency results in postmenopausal osteoporosis by
      increasing the rate of bone loss. The mechanism responsible for the effects of
      estrogen on osteoclasts is still unclear. MATERIALS AND METHODS: The potential of
      mononuclear cells from cord blood or bone marrow to differentiate into mature
      osteoclasts when co-cultured with human osteoblast cells was investigated. The
      effects of estrogen on osteoclastogenesis and osteoclast activity were also
      examined. RESULTS: Macrophage markers CD11b and CD14 were downregulated and
      vitronectin receptor was upregulated during 28 days' co-culture of mononuclear
      cells and human osteoblasts. Long-term co-culture resulted in the formation of
      numerous large tartrate-resistant acid phosphatase-positive multinucleated cells
      capable of resorption of bone slices. After incubation for 28 days, the addition
      of 17beta-estradiol caused a significant decrease in the expression of
      vitronectin receptor and tartrate-resistant acid phosphatase-positive
      multinucleated cells in cultures derived from both bone marrow and cord blood. A
      significant decrease in bone resorption was also noted in the presence of
      estrogen. CONCLUSION: Estrogen not only suppresses osteoclastogenesis but also
      inhibits the activity of osteoclasts.

PMID- 20045756
TI  - Unique biological properties and application potentials of CD34+ CD38- stem cells
      from various sources.
AB  - OBJECTIVE: Somatic CD34+ CD38- stem cells can differentiate into cells of
      hematopoietic and endothelial lineages and have been clinically used to treat
      diseases. These stem cells can be obtained from cord blood (CB), bone marrow or
      granulocyte-macrophage colony-stimulating factor-mobilized peripheral blood.
      Unmasking genes differentially expressed in hematopoietic stem cells (HSCs) from
      different anatomic locations can improve our understanding of their basic
      biological features and help in clinical decision making when applying different
      HSCs. MATERIALS AND METHODS: We performed microarray analysis on human CD34+ CD38
      HSCs isolated from CB, bone marrow and peripheral blood. Systems biology and
      advanced bioinformatics tools were used to better understand the biological
      modules and genetic networks accompanying each HSC subtype. RESULTS: We
      identified HSC genes differentially expressed in various HSCs and found them to
      be involved in critical biological processes such as cell cycle regulation, cell
      motility, and endogenous antigen presentation. Among these three HSC types, HSCs
      from CB expressed the fewest rejection and immune response-associated genes,
      thereby showing the best potential as a transplantation source. Analysis of HSC
      enriched genes using systems biology tools revealed a complex genetic network
      functioning in different CD34+ CD38- cells, in which several genes act as hubs,
      such as MYC in CB HSCs and hepatic growth factor in bone marrow HSCs, to maintain
      the stability or connectivity of the whole network. CONCLUSION: This study
      provides the foundation for a more detailed understanding of CD34+ CD38- HSCs
      from different sources, and reveals the potentials of different HSCs for
      different clinical applications.

PMID- 20045757
TI  - The relationship between human papillomavirus and Epstein-Barr virus infections
      in relation to age of patients with cervical adenocarcinoma.
AB  - OBJECTIVE: To examine the relationship between human papillomavirus (HPV) and
      Epstein-Barr virus (EBV) infections in relation to age of patients with cervical
      adenocarcinoma. MATERIALS AND METHODS: Thirty samples of human cervical
      adenocarcinoma tissue were collected from the surgical pathology archive at
      Taipei Veterans General Hospital from 1996 to 2008. All samples were examined for
      EBV, HPV-16 and HPV-18 E6 DNA by conventional and real-time quantitative
      polymerase chain reaction assays. RESULTS: HPV-16 DNA was detected in 10 cases
      (33.3%), HPV-18 DNA in 12 cases (40%), and EBV DNA in three cases (10%); there
      were negative findings in seven cases (23.3%). EBV combined with HPV-16 or HPV-18
      was also detected in one case each. No link could be demonstrated between HPV and
      EBV in endocervical lesions. When 20 patients 45 years old were compared with 10
      patients > 45 years old, HPV-18 E6 DNA was detected in 45% vs. 30% (9/20 vs.
      3/10), HPV-16 E6 DNA in 40% vs. 20% (8/20 vs. 2/10), EBV DNA in 10% vs. 10% (2/20
      vs. 1/10), and no virus DNA was detected in 10% vs. 50% (2/20 vs. 5/10). HPV and
      EBV were significantly more common in younger women (p < 0.001). CONCLUSION: HPV
      18 plays a major role in adenocarcinomas at any age. A high prevalence of HPV DNA
      is significantly associated with cervical adenocarcinoma, especially in younger
      women. The results do not support a role for EBV in cervical adenocarcinogenesis
      or any relationship between EBV and HPV infection in adenocarcinoma.

PMID- 20045758
TI  - Comparison of the efficacy of two vaginal progesterone formulations, Crinone 8%
      gel and Utrogestan capsules, used for luteal support in blastocyst stage embryo
      transfers.
AB  - OBJECTIVE: To compare the efficacy of two vaginal progesterone formulations,
      Crinone gel and Utrogestan capsules, for luteal phase support in blastocyst stage
      embryo transfers. MATERIALS AND METHODS: We analyzed 460 consecutive cycles in
      patients undergoing in vitro fertilization/intracytoplasmic sperm injection
      (IVF/ICSI)-blastocyst transfer (BT) treatment at our institution between January
      2004 and December 2007. Patients applied either Crinone 8% vaginal gel (90 mg,
      once daily) or Utrogestan vaginal capsules (200 mg, four times daily) for luteal
      supplementation. Progesterone was administered from the day of oocyte retrieval
      to pregnancy confirmation. Clinical pregnancy and implantation rates were the
      main outcome measures. RESULTS: The clinical pregnancy rate (58.7% vs. 44.3%) and
      implantation rate (32.04% vs. 23.89%) were significantly higher in the Crinone
      group compared with the Utrogestan group after IVF/ICSI-BT treatment. CONCLUSION:
      Luteal phase support with Crinone 8% vaginal gel (90 mg daily) resulted in better
      clinical pregnancy and implantation rates than Utrogestan vaginal capsules (200
      mg, four times daily) in IVF/ICSI-BT cycles.

PMID- 20045760
TI  - Prevalence of urinary frequency among women aged 60 years and older in Taiwan.
AB  - OBJECTIVE: To evaluate the prevalence of daytime urinary frequency among
      Taiwanese women aged 60 years and older. MATERIALS AND METHODS: There were an
      estimated 1.25 million female residents aged 60 years and over in Taiwan in 2000.
      A sample of 2,410 women was selected using a multistage random sampling method.
      Face-to-face visits with 1,523 women were completed by trained professional
      interviewers within 3 months of the subjects selection. Questions about urinary
      frequency and other lower urinary tract symptoms, sociodemographics,
      reproduction, and medical and surgical histories were recorded. The factors were
      assessed by frequency and Pearson's Chi-squared test using a significance level
      of < 0.05. RESULTS: The prevalence of urinary frequency in Taiwanese women aged
      60 years and over was 18.8% (286/1,521). The response rate was 85.0%
      (1,521/1,789). For those who complained of frequency, 45.8% voided 8-15 times a
      day, 37.8% voided 16-23 times a day, 1.7% voided 24-31 times and a day, and 14.7%
      voided more than 31 times a day. The prevalence of urinary frequency was
      significantly associated with age (p < 0.001). CONCLUSION: Urinary frequency is a
      common symptom in menopausal women and is significantly related to age. More than
      half of the women interviewed experienced intervals of < 1 hour between visits to
      the restroom during the day.

PMID- 20045759
TI  - Management of ovarian cysts by laparoscopic extracorporeal approach using single
      ancillary trocar.
AB  - OBJECTIVE: This prospective study aimed to evaluate an alternative laparoscopic
      extracorporeal approach for the treatment of benign ovarian cysts. MATERIALS AND
      METHODS: The initial study population included 243 patients diagnosed with benign
      ovarian masses. Two patients with suspected malignancies and 21 patients with
      technical difficulties secondary to severe, dense pelvic adhesions were excluded
      from the study, and the final study population, therefore, comprised 220
      patients. A primary 10-mm trocar was inserted, followed by a second incision on
      the side of the cyst and the introduction of an ancillary 5-mm trocar. The cystic
      content was aspirated using a needle. The capsule was held using an endograsper
      inserted through the ancillary trocar. The capsule was extracted from the
      abdomen. The 5-mm trocar and the endograsper were removed from the abdomen
      simultaneously. The capsule was completely detached. Homeostasis was performed
      and the ovary was then released. RESULTS: The mean duration of the operation was
      20 +/- 5 minutes. The size of the cysts ranged from 5 cm to 15 cm (mean, 8.4 +/-
      2.6 cm). The pathologies of the cysts were simple cyst in 86 cases, endometrioma
      in 68, serous cyst in 57, mucinous cyst in eight and borderline in one. The
      perioperative complication rate was 2.27%. CONCLUSION: This technique does not
      require the use of two or more ancillary trocars or widening of the trocar
      incision. The duration of surgery can be shortened considerably and complete
      excision of the cystic capsule can be performed. Homeostasis was achieved using 3
      0 polyglactin sutures. No electrocoagulation was required.

PMID- 20045761
TI  - Unbalanced and balanced acrocentric rearrangements involving chromosomes other
      than chromosome 21 at amniocentesis.
AB  - OBJECTIVE: To investigate unbalanced and balanced acrocentric rearrangements
      involving chromosomes other than chromosome 21 at amniocentesis. MATERIALS AND
      METHODS: From January 1987 to September 2009, 31,194 amniocenteses were performed
      at Mackay Memorial Hospital, Taipei, Taiwan. Two cases with unbalanced
      acrocentric rearrangements involving chromosomes other than chromosome 21 from
      two families, and 24 cases with balanced acrocentric rearrangements involving
      chromosomes other than chromosome 21 from 21 families were diagnosed and
      investigated. RESULTS: We detected i(13q13q), +13 (one case), rob(13q14q), +13
      (one case), rob(13q14q) (16 cases), rob(14q15q) (five cases), rob(13q15q) (one
      case), rob(15q22q) (one case), and mosaic rob(14q22q) (one case). Of the 25 cases
      that underwent parental cytogenetic investigation, six arose de novo and 19 were
      inherited (10 maternal and nine paternal). The 16 families with an inherited
      Robertsonian translocation included rob(13q14q) (11 families), rob(14q15q) (four
      families), and rob(15q22q) (one family). Of these 16 families, only two had known
      parental carrier status prior to the first amniocentesis, while the other 14 were
      aware of a parental carrier status only after prenatal diagnosis of a fetus with
      a heterologous Robertsonian translocation. The 18 fetuses with balanced
      heterologous Robertsonian translocations inherited them from six maternal
      carriers of rob(13q14q), four paternal carriers of rob(13q14q), four paternal
      carriers of rob(14q15q), and one maternal carrier of rob(15q22q). Neither UPD14
      nor UPD15 was detected in any of the 16 cases tested for UPD. CONCLUSION:
      Concerning acrocentric rearrangements involving chromosomes other than chromosome
      21, we found a frequency of 0.0064% for unbalanced rearrangements and 0.0769% for
      balanced rearrangements at amniocentesis in this study. rob(13q14q) was the most
      common and rob(14q15q) the second most common rearrangement. Of the families with
      an inherited translocation, 87.5% were aware of parental carrier status only
      after prenatal diagnosis of a fetus with a translocation by amniocentesis.

PMID- 20045762
TI  - Surgical blood loss and laparoscopic-assisted vaginal hysterectomy.
AB  - OBJECTIVE: This study aimed to elucidate the possible relationship between
      surgical blood loss (SBL) and medical outcomes of laparoscopic-assisted vaginal
      hysterectomy (LAVH). MATERIALS AND METHODS: Patients who underwent LAVH performed
      by the same surgeon for benign gynecologic diseases from 2004 to 2006 were
      analyzed retrospectively. Patients were divided into two groups according to the
      amount of SBL (< 150 mL or > or = 150 mL, 75th percentile of mean SBL). Clinical
      medical outcomes of all women were analyzed to identify the effects of SBL during
      LAVH. RESULTS: A total of 133 women with benign gynecologic disease were
      included. Group 1 (SBL < 150 mL) consisted of 108 patients and Group 2 (SBL > or
      = 150 mL) consisted of 25 patients. The mean operative time for patients with SBL
      > or = 150 mL was 36.1 minutes longer than that for patients with SBL < 150 mL (p
      < 0.001). Mean hospital stay, mean shift in serum hemoglobin, mean shift in serum
      hematocrit and mean flatulence relief time were not significantly different
      between the two groups. CONCLUSION: Greater SBL (> or = 150 mL) during LAVH was
      significantly associated with longer operating time, but had no detrimental
      effect on short-term surgical outcomes. Thus, efforts to minimize intraoperative
      bleeding and so reduce operative time will be beneficial for women undergoing
      LAVH.

PMID- 20045763
TI  - Down syndrome due to unbalanced homologous acrocentric rearrangements and its
      recurrence in subsequent pregnancies: prenatal diagnosis by amniocentesis.
AB  - OBJECTIVE: To present our experience of amniocentesis for the prenatal diagnosis
      of Down syndrome due to unbalanced homologous acrocentric rearrangements and its
      recurrence in subsequent pregnancies. CASE REPORT: From January 1987 to September
      2009, six cases with rea(21q21q) Down syndrome were diagnosed among 31,194
      patients who underwent amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan.
      Cytogenetic analysis of parental blood lymphocytes was performed in each case,
      and polymorphic DNA markers were used to investigate the nature of the aberrant
      chromosome. Three of the six cases were associated with recurrence in subsequent
      pregnancies. The rea(21q21q) Down syndrome was associated with advanced maternal
      age in three cases, a previous child with rea(21q21q) Down syndrome in three
      cases, an abnormal maternal serum screening result in one case, and an abnormal
      ultrasound finding in one case. All six cases arose de novo. Among the six cases
      with molecular analysis results, all had isochromosome 21, five of which were
      determined to be of maternal origin. CONCLUSION: We found a frequency of 0.019%
      for rea(21q21q) Down syndrome in patients undergoing amniocentesis. Down syndrome
      caused by the homologous rearrangement rea(21q21q) can be associated with
      recurrence. Prenatal diagnosis of rea(21q21q) Down syndrome should include
      extensive cytogenetic and molecular analyses of the parents and probands.

PMID- 20045764
TI  - Prenatal diagnosis of monosomy 17p (17p13.3-->pter) associated with
      polyhydramnios, intrauterine growth restriction, ventriculomegaly, and Miller
      Dieker lissencephaly syndrome in a fetus.
AB  - OBJECTIVE: To present the prenatal magnetic resonance imaging (MRI) and
      ultrasound findings of Miller-Dieker lissencephaly syndrome (MDLS) associated
      with chromosome 17p13.3 deletion in a fetus. CASE REPORT: A 30-year-old,
      primigravid woman was referred to the hospital at 31 weeks' gestation because of
      intrauterine growth restriction (IUGR) and polyhydramnios detected by ultrasound.
      The pregnancy was uneventful until 31 weeks of gestation when IUGR and
      polyhydramnios were first noted. Level II ultrasound at 31 weeks' gestation
      showed fetal biometry equivalent to 27 weeks' gestation, an amniotic fluid index
      of 33.4 cm, ventriculomegaly, and abnormal sulcal development with absence of
      gyri and sulci, and a shallow Sylvian fissure. Other organs were unremarkable.
      Subsequent amniocentesis revealed a 46,XY,del(17)(p13.3) karyotype. Ultrafast
      fetal MRI performed at 34 weeks of gestation revealed agyria/pachygyria, a figure
      eight appearance of the brain, a wide and shallow Sylvian fissure, enlarged
      subarachnoid space, ventriculomegaly, and polyhydramnios. At 35 weeks' gestation,
      a 1,346-g male baby was delivered with facial dysmorphism, characteristic of
      MDLS. Postnatal MRI confirmed the prenatal diagnosis. CONCLUSION: Polyhydramnios,
      IUGR and ventriculomegaly are important prenatal ultrasound markers of MDLS.
      Prenatal diagnosis of these markers should include a detailed investigation of
      cerebral sulci and fissures, and genetic analysis for MDLS. Fetal MRI is helpful
      for the diagnosis of lissencephaly.

PMID- 20045765
TI  - Appendiceal mucocele mimicking a cystic right adnexal mass.
AB  - OBJECTIVE: Appendiceal mucocele is formed by cystic dilatation, abnormal mucinous
      secretion and epithelial proliferation of the appendiceal lumen. Mucocele may be
      a finding in cases of benign or malignant neoplasms, and can lead to the
      development of pseudomyxoma peritonei. CASE REPORT: A 71-year-old woman presented
      with a 3-day history of right lower abdominal pain radiating to her right thigh.
      A simple 5 x 7 cm cyst with smooth borders and a thick capsule was detected in
      the right adnexal area by transvaginal ultrasonography. Magnetic resonance
      imaging identified a 4 x 8 cm cystic lesion in the area of the right ovary. The
      patient was admitted to our clinic with an initial diagnosis of adnexal cyst,
      later found to be appendiceal mucocele. CONCLUSION: The signs and symptoms of
      appendiceal mucocele are not specific. Because of its anatomic position, it
      should be considered in the differential diagnosis of adnexal masses.

PMID- 20045766
TI  - Extrauterine displaced intrauterine devices: when should they be surgically
      removed?

PMID- 20045767
TI  - Recurrent ectopic pregnancy in the ipsilateral oviduct after prior laparoscopic
      partial salpingectomy.

PMID- 20045768
TI  - Recurrent ipsilateral ectopic pregnancy after partial salpingectomy.

PMID- 20045770
TI  - Herpes gestationis.

PMID- 20045769
TI  - Subcapital fracture of the hip in transient osteoporosis of pregnancy.

PMID- 20045771
TI  - Favorable obstetric outcome in a fetus diagnosed with umbilical vein varix at 22
      weeks' gestation.

PMID- 20045772
TI  - Intravaginal foreign bodies placed in the vagina to treat uterine prolapse
      retained for 35 years.

PMID- 20045773
TI  - Trisomy 13 mosaicism associated with cyclopia and cystic hygroma.

PMID- 20045774
TI  - 22q11.2 microdeletion in a fetus with double-outlet right ventricle, pulmonary
      stenosis and a ventricular septal defect: prenatal diagnosis by array comparative
      genomic hybridization.

PMID- 20045775
TI  - Terminal 2q deletion and distal 15q duplication: prenatal diagnosis by array
      comparative genomic hybridization using uncultured amniocytes.

PMID- 20045776
TI  - Limb-body wall complex in one fetus of a dizygotic twin pregnancy conceived by
      egg donation, in vitro fertilization and embryo transfer: prenatal diagnosis and
      literature review.

PMID- 20045777
TI  - Prenatal group B streptococcus test using real-time polymerase chain reaction.

PMID- 20045779
TI  - Zonisamide in West syndrome: an open label study.
AB  - AIMS: Infantile spasms are usually resistant to conventional antiepileptic drugs.
      Although adrenocorticotropic hormones or vigabatrin are regarded as standard
      agents for the treatment of infantile spasms, there are still limitations of
      their use. We determined the efficacy and tolerability of high-dose zonisamide in
      patients with recent-onset infantile spasms. METHODS: Seventeen patients with
      infantile spasms, who were admitted to our hospital between October 2005 and
      November 2007, were eligible for enrollment within two months of diagnosis.
      Zonisamide was administered at a starting dose of 2-8 mg/kg/day, increasing by 2
      5 mg/kg/day every three to four days until the seizures disappeared or the dose
      reached 30 mg/kg/day. Complete response was defined as clinical cessation of
      infantile spasms over 28 consecutive days and disappearance of hypsarrhythmia by
      EEG analysis. RESULTS: Of the 17 treated patients (nine who received initial
      monotherapy and eight add-on therapy), five of 12 (42.0%) cryptogenic patients
      and two of five (40.0%) symptomatic patients showed complete disappearance of
      spasms. The maximum daily dose was 10-28 mg/kg, and the effective daily dose was
      10-22 mg/kg. Mean time period before disappearance of spasms and hypsarrhythmia
      was eight days. Seizure recurrence was observed in three of the seven patients
      who showed complete disappearance of spasms. Adverse effects included
      irritability in four patients and poor oral intake in two patients. CONCLUSION:
      Although further study of zonisamide is warranted, high-dose zonisamide can be
      effective and safe in some infants with newly diagnosed West syndrome.

PMID- 20045780
TI  - Myoclonic status epilepticus in juvenile myoclonic epilepsy.
AB  - BACKGROUND: Myoclonic status epilepticus (MSE) is rarely found in juvenile
      myoclonic epilepsy (JME) and its clinical features are not well described. We
      aimed to analyze MSE incidence, precipitating factors and clinical course by
      studying patients with JME from a large outpatient epilepsy clinic. METHODS: We
      retrospectively screened all patients with JME treated at the Department of
      Neurology, Medical University of Innsbruck, Austria between 1970 and 2007 for a
      history of MSE. We analyzed age, sex, age at seizure onset, seizure types, EEG,
      MRI/CT findings and response to antiepileptic drugs. RESULTS: Seven patients
      (five women, two men; median age at time of MSE 31 years; range 17-73) with MSE
      out of a total of 247 patients with JME were identified. The median follow-up
      time was seven years (range 0-35), the incidence was 3.2/1,000 patient years.
      Median duration of epilepsy before MSE was 26 years (range 10-58). We identified
      three subtypes: 1) MSE with myoclonic seizures only in two patients, 2) MSE with
      generalized tonic clonic seizures in three, and 3) generalized tonic clonic
      seizures with myoclonic absence status in two patients. All patients responded
      promptly to benzodiazepines. One patient had repeated episodes of MSE.
      Precipitating events were identified in all but one patient. Drug withdrawal was
      identified in four patients, one of whom had additional sleep deprivation and
      alcohol intake. Two patients received inappropriate treatment (carbamazepine,
      phenytoin). CONCLUSIONS: MSE is a rare event in JME. Precipitating factors are
      commonly identified and for such cases the treatment response and outcome are
      excellent, in contrast to other cases with unknown causes.

PMID- 20045781
TI  - Convulsive syncope: a condition to be differentiated from epilepsy.
AB  - The clinical presentation of epilepsy and syncope can be confusingly similar. We
      present a patient with reflex syncopal episodes that mimic seizures using video
      EEG recordings. During the episodes, head/eye deviations, automatisms and
      dystonic movements, suggesting an epileptic seizure, were observed. The EEG
      revealed diffuse slow waves when the patient lost consciousness and complete
      cessation of the cerebral activity occurred when the dystonic movements started.
      On ECG recordings, bradycardia, followed by complete asystolia lasting for 40
      seconds, was observed. We conclude that the differential diagnosis of epilepsy
      and syncope can be quite misleading and clinical features may not always be
      reliable. In cases where diagnosis is uncertain, circulatory and cardiac causes
      should always be kept in mind and video-EEG with simultaneous cardiac recordings
      are mandatory for accuracy of diagnosis.

PMID- 20045782
TI  - Clinical practice guidelines for cancer care: what are they for?

PMID- 20045784
TI  - Molecular mechanisms behind the resistance of cisplatin in germ cell tumours.
AB  - Cisplatin has been one of the principal chemotherapy agents for the last 30 years
      and is still used widely in the treatment of testicular, ovarian, lung, head and
      neck, bladder and several other tumours. Resistance to chemotherapeutic agents is
      a major obstacle for successful treatment. Treatment effect on germ cell tumours
      (GCTs) is more successful than in adults suffering from almost any other solid
      tumour, but resistance still appears in 20% of patients with metastatic disease.
      However, because of the young age of patients and few data regarding the process
      of becoming resistant, this situation is still a challenge. In this review we are
      going to analyse the published literature on cisplatin resistance in GCTs and
      explain the initiatives that the Spanish Germ Cell Cancer Group (GG) is taking to
      try to elucidate the molecular mechanisms behind this process.

PMID- 20045785
TI  - Aurora kinase inhibitors: a new class of drugs targeting the regulatory mitotic
      system.
AB  - The present review gives a perspective on the Aurora kinase family members, their
      function in normal cells, their role in cancer progression as well as their
      potential as target for anticancer treatment. Mitosis has been an important
      target for anticancer therapy development, leading to some specific drugs mainly
      addressing Tubulines, as a key structure of the mitotic spindle. Vinca alkaloids,
      taxanes or epotilones are good examples of conventionally developed antimitotic
      agents. However, novel classes of antineoplastic drugs are being studied,
      targeting the regulatory system that controls functional aspects of mitosis, such
      as Aurora or Polo-like kinases or Kinespondin inhibitors. The specific role of
      the different Aurora kinase proteins as regulator enzymes of the mitotic process
      in normal cells is discussed. Some of the mechanisms that link Aurora
      overexpression with cancer are also considered. Thereafter, the clinical and
      preclinical development of the different Aurora kinase inhibitors is presented.
      This is nowadays a very active area of therapeutic research and at least, sixteen
      new compounds are being studied as potential antineoplastic drugs. Most of them
      are in a very early phase of clinical development. However, we summarized the
      most recently published findings related with these drugs: main characteristics,
      way of administration, dose limiting toxicities and recommended doses for further
      studies. Another important aspect in Aurora kinase inhibition is the study and
      validation of potential biomarkers to optimize the clinical development. Several
      studies included pharmacodynamic assessments in normal blood cells, skin or/and
      tumor biopsies. Several proposals included a higher mitotic index, a decreased
      number of mitosis with bipolar spindles or normal alignment of chromosomes and
      inhibition of histone H3 phosphorylation. Future strategies and challenges for
      trials with Aurora kinase inhibitors are also discussed.

PMID- 20045786
TI  - Laparoscopic radical cystectomy.
AB  - Open radical cystectomy with lymph node dissection remains the gold standard
      treatment for recurrent, high-grade, non-muscle-invasive and for muscle-invasive
      bladder cancer. The excellent perioperative and long-term results provided by
      laparoscopic surgery and the advances in instrumentation design have naturally
      paved the way for development of laparoscopic radical cystectomy (LRC). In this
      review, surgical and long-term oncological outcomes of LRC are analysed. The
      advantages of this technique compared with open surgery are described. The
      differences between pure laparoscopic technique or laparoscopic cystectomy and
      extracorporeal urinary diversion have also been analysed.

PMID- 20045788
TI  - Lung Cancer OncoGuia: surgical pathology report guidelines.

PMID- 20045789
TI  - Vesical instillations of hyaluronic acid to reduce the acute vesical toxicity
      caused by high-dose brachytherapy do not affect the survival: a five-year follow
      up study.
AB  - OBJECTIVE: To determine whether the intravesical use of hyaluronic acid (HA)
      reduces acute and late vesical toxicity induced by radiotherapy. METHODS: Single
      centre retrospective study of patients diagnosed with cervical and endometrial
      cancer treated with brachytherapy (BT) with or without intravesical instillation
      of HA. Patients were assigned consecutively to the two treatment groups. Forty
      milligrams of HA was instilled intravesically for approximately 30 min prior to
      each BT session. Rates of acute and late vesical toxicity were recorded using the
      RTOG criteria. RESULTS: Ninety-five clinical histories were reviewed (48 with HA
      instillation and 47 without). Surgery had been performed in 85.3% of cases,
      external radiotherapy in 76.8% and chemotherapy in 25.3%. There were no
      significant differences between groups with regard to the total number of BT
      sessions, dose per session, total dose or biological equivalent dose. In all the
      sessions the percentage of patients presenting acute vesical toxicity was lower
      in the HA group, the differences being statistically significant (p<0.05) after
      the 2nd (20.8% vs. 40.4%) and 4th sessions (10.9% vs. 31.9%). No patients in the
      HA group presented vesical toxicity after six months of follow-up. Over the whole
      study period, the percentage of patients presenting vesical toxicity of degree 2
      or more was significantly lower in the HA group (2.08% vs. 12.8%; p<0.05).
      CONCLUSION: Vesical instillations of HA decrease the incidence and the degree of
      acute vesical toxicity induced by high-dose BT, and reduce the percentage of
      patients that develop toxicity of degree 2 or more.

PMID- 20045787
TI  - Lung Cancer OncoGuia.

PMID- 20045790
TI  - Long-term results of neoadjuvant chemotherapy and combined chemoradiotherapy
      before surgery in the management of locally advanced oesophageal cancer: a single
      centre experience.
AB  - INTRODUCTION: Neoadjuvant chemoradiotherapy before surgery is an option in the
      treatment of locally advanced resectable oesophageal cancer (EC). However
      toxicity is substantial and the improvement in overall survival (OS) with this
      approach is controversial. METHODS: This was a prospective, single-centre study
      of neoadjuvant chemotherapy and concomitant chemoradiotherapy with CDDP and 5-FU
      and 50.4 Gy of external radiotherapy before possible radical surgery in patients
      with locally advanced resectable EC. If surgery was not possible, a second-phase
      radiotherapy boost of 10 Gy and one cycle of modified dose chemotherapy were
      used. RESULTS: Seventy-three patients included between 1998 and 2007: 96% males,
      median age 61, 83% squamous cell carcinomas, 23% lower third tumours, 36% stage
      II and 54% stage III and 47% local lymph node involvement. Eighty-six percent
      completed the combined protocol. Main grade 3-4 toxicities: mucositis (19%) and
      infections (8%); 4 toxic deaths. Clinical response rates: complete response 54%,
      partial response 27%, stable disease 8%. Twenty-five patients proceeded to
      surgery, with radical resection in 24. Pathological response rate: complete
      response 32%, partial response 52%, progression 16%. There were 7 postoperative
      deaths and 16 of 34 patients that did not have surgery received the second-phase
      RT boost. Survival analysis: Median follow-up of 64 months (range 6-134 months).
      Median OS of 10.33 months. 2-year and 5-year OS of 22 and 16%. The only
      significant prognostic factor in OS is the clinical complete response rate: 13.9
      vs. 7.7 months (p=0.0049). CONCLUSIONS: Our protocol offers a high rate of
      clinical activity although it is relatively toxic and seems to increase the
      postoperative mortality, which would blunt any small improvement in survival. The
      achievement of a complete response is a powerful prognostic factor.

PMID- 20045791
TI  - Use of pegfilgrastim support on day 9 to maintain relative dose intensity of
      chemotherapy in breast cancer patients receiving a day 1 and 8 CMF regimen.
AB  - AIM: In several commonly used regimens, chemotherapy doses are split across
      different days of the cycle. We aimed to determine the feasibility of growth
      factor support with once-per-cycle pegfilgrastim in this setting. METHODS: This
      phase II study in breast cancer patients assessed the utility of a single 6 mg
      subcutaneous dose of pegfilgrastim administered on day 9 of an intravenous (IV)
      "split" CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2) and 5
      fluorouracil 600 mg/m(2)) chemotherapy regimen administered on days 1 and 8 and
      repeated every 28 days for 6 cycles. RESULTS: Fifty-eight patients were enrolled,
      with 49 completing the study. For the primary endpoint, 48 patients (83%)
      received >or=85% of the relative dose intensity (RDI) of chemotherapy over all 6
      cycles (95% confidence interval [CI], 71-91%). Across all chemotherapy cycles, 41
      patients (71%) received all scheduled cycles on time and most patients (n=49,
      84%) received >or=85% of the planned dose of all chemotherapy agents in all
      cycles. In total, 295/319 cycles (92%) were delivered on schedule and >or=85% of
      the planned dose of all chemotherapy agents were administered in 309/319 cycles
      (97%). Febrile neutropenia was reported in only 2 patients (3%). There were no
      grade 4 adverse events related to pegfilgrastim. DISCUSSION: Day 9 pegfilgrastim
      administration was well tolerated and provided effective protection against
      neutropenia in patients receiving IV CMF on days 1 and 8, allowing chemotherapy
      to be delivered on time and at the scheduled dose in most patients.

PMID- 20045792
TI  - Benefit of sperm freezing before radical orchiectomy.
AB  - A patient with a unilateral testis tumour who had been treated with radical
      orchiectomy was referred to our centre. He was oligospermic before orchiectomy
      and needed chemotherapy because of abnormal tumour markers after the
      aforementioned operation. He did not have any sperm suitable for freezing.
      Because of a lack of information about the spermatogenic abilities in the other
      testis, it is advisable to freeze sperm prior to orchiectomy at least in patients
      with semen analysis disorders.

PMID- 20045793
TI  - Dramatic complete response in patient with lung adenocarcinoma.
AB  - The poor prognosis of non-small-cell lung cancer (NSCLC) is changing thanks to
      the constant development of new treatments and the introduction of target
      therapies, even in stage IV disease. This patient had bone metastases when he was
      diagnosed. Maintenance treatment, a much discussed topic nowadays, achieved a
      dramatic complete response.

PMID- 20045794
TI  - Primary breast synovial sarcoma: a rare primary breast neoplasm.
AB  - A primary synovial sarcoma based on the breast is rare. The usual tumours on the
      breast are carcinomas. Synovial sarcomas account for about 6-9% of soft tissue
      sarcomas and most commonly develop in the extremity of young adults (80%). The
      other 20% of synovial sarcomas can arise in non-extremity sites (trunk 8%,
      retroperitoneal/ abdominal 7%, head and neck 5%) but synovial sarcomas can
      develop in almost any other anatomical location. We report a case of a young
      woman who presented with a suspected common breast tumour and started treatment
      of this tumour with carcinoma neoadjuvant chemotherapy. We were surprised when
      the pathologist identified a synovial sarcoma in the histopathology study.

PMID- 20045795
TI  - Where postmenopausal hormone therapy stands today.

PMID- 20045796
TI  - Hormones, hormonal agents, and neuropeptides involved in the neuroendocrine
      regulation of sleep in humans.
AB  - Sleep is an essential ubiquitous biological process, a periodical state of
      quiescence in which there is minimal processing of sensory information and no
      interaction with conspecifics or the environment. Despite relevant research on
      sleep structure and testing of numerous endogenous sleep-affecting chemicals,
      questions as to the precise mechanisms and functions of sleep remain without
      satisfactory responses. The purpose of this review is to report on current
      evidence as regards the effect of several endogenous and exogenous hormones,
      hormonal agents, and neuropeptides on sleep onset or wake process, when
      administered in humans in specific doses and via different routes. The actions of
      several peptides are presented in detail. Some of them (growth hormone releasing
      hormone, ghrelin, galanin, neuropeptide Y) seem to promote sleep, whereas others
      (corticotropin, somatostatin) impair its continuity.

PMID- 20045797
TI  - The 'rings of fire' and thyroid cancer.
AB  - Several studies have revealed an increased incidence of thyroid cancer in
      volcanic areas around the world. Hawaii and the Philippines on the rim of the
      Pacific Ocean, where the greatest number of volcanoes are located at convergent
      plate boundaries, are among the regions with the highest incidence of thyroid
      carcinoma worldwide. Iceland is another region also rich in volcanoes in which
      the highest incidence of thyroid cancer in Europe is found. The common
      denominator of these regions is their numerous volcanoes and the fact that
      several constituents of volcanic lava have been postulated as being involved in
      the pathogenesis of thyroid cancer. This article aims at presenting pertinent
      data that could link a volcanic environment to thyroid cancer.

PMID- 20045799
TI  - The Pro12Ala polymorphism of the PPAR-gamma gene is not associated with the
      polycystic ovary syndrome.
AB  - OBJECTIVE: Insulin resistance is a key factor in the pathogenesis of polycystic
      ovary syndrome (PCOS). Peroxisome proliferator-activated- receptor-gamma (PPAR
      gamma) has been implicated in insulin resistance and adiposity. The aim of the
      study was to investigate the possible involvement of the Pro12Ala polymorphism of
      the PPAR-gamma gene in the pathogenesis of PCOS. DESIGN: We studied 180 women
      with PCOS and 140 healthy controls. Body mass index (BMI) was recorded. Blood
      samples were drawn after overnight fasting and serum glucose, insulin, lipid and
      hormonal profiles were determined. The fasting glucose/insulin ratio and HOMA
      index were calculated. Moreover, 100 women with PCOS underwent a 75g oral glucose
      tolerance test and the area under the curve for insulin and glucose was
      estimated. DNA was extracted from peripheral blood leucocytes and the Pro12Ala
      polymorphism was genotyped. RESULTS: The PPAR-gamma genotypes were found to be in
      the Hardy-Weinberg equilibrium in both study groups. No difference was found in
      the distribution of the Pro12Ala polymorphism between PCOS and controls. Insulin
      resistance indices and lipid and hormonal profile were not different among the
      various genotypes of the Pro12Ala polymorphism. CONCLUSIONS: The Pro12Ala
      polymorphism of the PPAR-gamma gene is not involved in the pathogenesis or the
      phenotypic expression of PCOS.

PMID- 20045798
TI  - Extensive personal experience. Validation of prolactin levels in menstrual
      disorders and in prolactinomas.

PMID- 20045800
TI  - Comparison of two fixed activities of radioiodine therapy (370 vs. 555 MBq) in
      patients with Graves' disease.
AB  - OBJECTIVE: Radioiodine therapy is the most commonly used therapy for patients
      with Graves' disease (GD) in the United Kingdom. It is considered safe, effective
      and relatively inexpensive. The aim of our study was to examine the outcome of
      131Iodine therapy in patients with GD when two different activities of 131Iodine
      were used. DESIGN: A retrospective audit was undertaken to compare the efficacy
      of 370 (10 millicuries) versus 555MBq (15 millicuries) radioiodine therapy in
      patients with Graves' disease over a period of ten years. RESULTS: Overall, 90%
      of the patients had a successful outcome from treatment with no significant
      difference in the success rate between the lower and higher activities or between
      genders. CONCLUSIONS: 555 MBq of radioiodine was no more effective than 370 MBq
      in managing patients with Graves' disease. We therefore recommend that the higher
      activity should not be routinely used in these patients.

PMID- 20045801
TI  - Effect of zinc supplementation on insulin resistance and components of the
      metabolic syndrome in prepubertal obese children.
AB  - OBJECTIVE: Zinc, an essential trace element and a component of many enzymes, is
      involved in the synthesis, storage and release of insulin. The aim of the present
      study was to assess the effect of zinc supplementation on insulin resistance and
      components of the metabolic syndrome in prepubertal obese children. DESIGN: This
      triple-masked, randomized, placebo-controlled cross-over trial was conducted
      among 60 obese Iranian children in 2008. Pertinent clinical findings, fasting
      serum glucose, insulin and lipid profile were assessed. Participants were
      randomly assigned to two groups of equal number; one group received 20mg
      elemental zinc and the other group received placebo on a regular daily basis for
      eight weeks. After a 4-week wash-out period, the groups were crossed over.
      RESULTS: The mean age of participants was 9.1 +/- 1.1 years. After receiving
      zinc, the mean fasting plasma glucose (FPG), insulin and HOMA-IR decreased
      significantly, while body mass index (BMI), waist circumference (WC), LDL-C and
      triglycerides (TG) did not significantly change. After receiving placebo, the
      mean FPG, insulin and HOMA-IR increased significantly, while BMI, WC, LDL-C and
      TG showed a non-significant increase. CONCLUSION: Besides lifestyle modification,
      zinc supplementation might be considered as a useful and safe additional
      intervention treatment for improvement of cardiometabolic risk factors related to
      childhood obesity.

PMID- 20045802
TI  - Predictors of amputation in diabetics with foot ulcer: single center experience
      in a large Turkish cohort.
AB  - OBJECTIVE: Prediction of diabetic foot ulcer outcome may be helpful for
      clinicians in optimizing and individualizing management strategy. The aim of the
      present study was to examine the possibility of predicting the outcome of
      patients with diabetic foot ulcers by using easily assessed clinical and
      laboratory parameters at baseline. DESIGN: In this observational study, data were
      collected prospectively in 670 consecutive diabetic foot ulcer episodes in 510
      patients examined between January 1999 and June 2008 and were used to evaluate
      potential predictors of amputation retrospectively. After exclusion of patients
      who did not come to the hospital for follow-up for a minimum of six months, data
      of 574 foot ulcer episodes were evaluated. RESULTS: Limb ischemia, osteomyelitis
      and presence of gangrene and ulcer depth, determined by the Wagner classification
      system, were the major independent predictors of overall and major amputations.
      Older age, presence of coronary artery disease, smoking and ulcer size were found
      to be associated with either overall or major amputations. Baseline levels of
      acute phase reactants (white blood cell count, polymorphonuclear leukocyte count,
      platelet count, erythrocyte sedimentation rate (ESR), serum C-reactive protein
      (CRP) and albumin) and decreased hemoglobin levels were associated with
      amputation risk. Multivariate analysis showed that one standard deviation
      increase in baseline CRP and ESR levels were independent predictors of overall
      and major amputations, respectively. CONCLUSIONS: The presence of limb ischemia,
      osteomyelitis, local and diffuse gangrene and ulcer depth were independent
      predictors of amputation. Baseline levels of ESR and CRP appeared to be helpful
      for clinicians in predicting amputation.

PMID- 20045803
TI  - Thyroid volume, selenium levels and nutritional habits in a rural region in
      Albania.
AB  - OBJECTIVE: Environmental factors are involved in goiter development. An increased
      number of goitrous patients were identified among outpatients in Gyrocaster, a
      mountainous region in Southwestern Albania. We examined possible associations of
      thyroid enlargement with nutritional factors. DESIGN: 112 consecutive patients,
      104 females, aged 52.8 +/-12.1 (mean+/-SD), who either were taking thyroxine
      (n=27) or were suspected to have thyroid disease were examined. Thyroid
      parameters and nutritional habits were recorded and serum selenium and urine
      iodine levels were determined; thyroid ultrasound was performed. RESULTS: The
      median thyroid volume (TV) was 20.4 ml (range 4.4-97.6). All consumed food was
      home-produced. TV correlated negatively with the frequency of lamb-goat meat and
      vegetables consumption (p=0.05 and p=0.03, respectively). Mean TV was
      significantly lower in those eating lamb-goat >1 times/week (21.4+/-13.3 vs
      31.9+/-23 ml, p<0.01). The association of TV with lamb meat consumption was
      independent of sex, education or occupation (p < 0.009). Selenium levels ranged
      from 30.6-138 microg/L (reference range 43-190). There was no association between
      selenium levels and TV. 43% of the subjects had TSH < 0.3 mU/L (those on
      thyroxine were excluded). Log TSH correlated negatively with TV and fT4 levels (p
      < 0.007), indicating the presence of autonomy (TSHRab positive in two subjects).
      Mean urinary iodine excretion was 99.8+/-35.3 microg/gr creatinine (normal >100).
      CONCLUSIONS: Nutritional factors may be involved in the development of goiter in
      Southwestern Albania. No role of selenium was found. The higher consumption of
      lamb-goat meat and vegetables, all non-industrialized, appeared to be protective.
      This finding may reflect better socioeconomic status, although this was not
      identified. Unrecognized subclinical hyperthyroidism, probably due to thyroid
      autonomy, was quite common.

PMID- 20045806
TI  - Pulmonary rehabilitation following acute exacerbation of chronic obstructive
      pulmonary disease.

PMID- 20045804
TI  - Effect of temozolomide in a patient with recurring oncocytic gonadotrophic
      pituitary adenoma.
AB  - The patient was a 70-year-old man with a recurrent pituitary tumor. Three
      surgeries were performed but the tumor recurred. Based on histologic,
      immunohistochemical and ultrastructural studies, the diagnosis of oncocytic
      gonadotrophic pituitary adenoma was made. The tumor was a macroadenoma partly
      immunopositive for LH. Immunohistochemistry for O6 Methylguanine-DNA Methyl
      Transferase (MGMT) showed an admixture of immunopositive and immunonegative
      cells. After recurrence following operations, the patient was treated with
      Temozolomide, an imidazotetrazine derivative, DNA-alkylating drug. Following
      Temozolomide administration the MRI demonstrated significant tumor necrosis. A
      few months later, the patient died of massive pulmonary embolism. No autopsy was
      performed. The present case indicates that benign, typically slow-growing
      pituitary adenomas of oncocytic gonadotrophic type may respond to Temozolomide
      even when the tumor consists of an admixture of MGMT immunopositive and
      immunonegative cells.

PMID- 20045807
TI  - What's in team rehabilitation care after arthroplasty for osteoarthritis? Results
      from a multicenter, longitudinal study assessing structure, process, and outcome.
AB  - BACKGROUND: Clinical course and outcome connected to rehabilitation after hip or
      knee arthroplasty have been studied extensively, but few studies have assessed
      the content of team rehabilitation care for these patients. OBJECTIVE: The
      purpose of this study was to provide a thorough description of the structure,
      process, and outcome of team rehabilitation care for patients with hip or knee
      arthroplasty for osteoarthritis. DESIGN: This was a multicenter, longitudinal
      observational study. METHODS: Patients (N=183) from 6 rehabilitation centers in
      Norway who were undergoing inpatient rehabilitation following hip or knee
      arthroplasty were included in the study. Structure and process components were
      recorded by participants and health care professionals in a patient diary.
      Participants also completed questionnaires regarding their experiences during
      their rehabilitation stay and recorded data for outcome measures at admission, at
      discharge, and 6 months after discharge. The main outcome measures were pain
      intensity and physical function, as assessed with the physical function scale of
      the Medical OUTCOMES: Study 36-Item Short-Form Health Survey (SF-36). RESULTS:
      Data were complete for 172 participants (94%) at discharge and for 148 patients
      (81%) at the 6-month follow-up. Health care professionals, physical therapists,
      nurses, and physicians were most often involved in team care. Occupational
      therapists, social workers, and psychologists were seldom part of the
      rehabilitation team. Exercises provided by physical therapists were the most
      common treatment modality. Patient education, massage, and manual therapy also
      frequently were provided. The participants were very satisfied with their care
      and its organization, information, and communication and with the availability of
      health care professionals. They were moderately satisfied with the social
      environment of the rehabilitation setting. The participants had large
      improvements in the outcome measures during the rehabilitation stay and at the 6
      month follow-up. LIMITATIONS: For typical physical therapy modalities such as
      exercises, electrotherapy, and acupuncture, there are limited descriptions and
      assessments of treatment doses. CONCLUSIONS: Current team rehabilitation care
      involves a traditional team with physical therapists, nurses, and physicians.
      Several types of treatment modalities are used, with greatest emphasis on
      physical training. This detailed description of current team rehabilitation
      practice might help clinicians and researchers in planning clinical trials within
      a rehabilitation setting, as well as in improving rehabilitation practice.

PMID- 20045808
TI  - Antimicrobial-resistant pathogens in animals and man: prescribing, practices and
      policies.
AB  - This meeting focused on infections in humans and animals due to methicillin
      resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)
      producing bacteria and Clostridium difficile, and their corresponding treatments.
      MRSA is predominantly a human pathogen, and molecular typing has revealed that
      certain clones have spread widely both between humans and from humans to animals.
      ESBL-producing bacteria, particularly those that express the CTX-M beta
      lactamases, have been disseminated worldwide. Whilst such strains are usually
      isolated from humans, some animal isolates also produce CTX-M enzymes. In humans,
      one clone of CTX-M-producing Escherichia coli, sequence type (ST)131, has been
      particularly successful. C. difficile, often ribotype 027, commonly colonizes the
      hospital environment and causes serious infections in humans. In animals,
      ribotype 078 is more often found, and is an important cause of diarrhoea in
      piglets. There is a concern that the numbers of MRSA or other antimicrobial
      resistant bacteria might increase further when human isolates become established
      in animals, as this can amplify the numbers of such bacteria by dissemination
      within animal groups with subsequent spread back to humans. Certain
      antimicrobials have been implicated in the selection of MRSA, ESBL-producing
      bacteria and predisposition to infection by C. difficile. Guidelines for
      treatment and prevention of infections by MRSA, ESBL-producing bacteria and C.
      difficile were discussed and evidence-based policies were recommended for both
      humans and animals.

PMID- 20045809
TI  - Sports and cardiac function 1: exercise is a potent stressor on the heart.

PMID- 20045810
TI  - Emerging and re-emerging infectious diseases: be prepared.

PMID- 20045811
TI  - Implants or pontics.

PMID- 20045812
TI  - Infant formula.

PMID- 20045813
TI  - Diving damage.

PMID- 20045814
TI  - Availability of optical coherence tomography.

PMID- 20045819
TI  - Accuracy and dimensional stability of extended-pour and conventional alginate
      impression materials.
AB  - BACKGROUND: The authors conducted a study to determine if two irreversible
      hydrocolloid impression materials (Cavex ColorChange, Cavex Holland BV, Haarlem,
      Netherlands; Jeltrate Plus Antimicrobial Dustless Alginate Impression Material,
      Dentsply Caulk, Milford, Del.) stored for five days were dimensionally accurate.
      METHODS: The authors modified Ivorine teeth (Columbia Dentoform, Long Island
      City, N.Y.) on a Dentoform model (1560 series model, Columbia Dentoform) to allow
      measurements of tooth and arch width. They made impressions and generated casts
      immediately and at five additional times. They recorded tooth and arch widths on
      the casts and compared the measurements with those for the standard model.
      RESULTS: Compared with measurements for the model, the greatest measured
      difference in casts was 0.003 inches for Cavex ColorChange (extended-pour
      alginate) and 0.005 inches for Jeltrate Plus Antimicrobial Dustless Alginate
      Impression Material (conventional alginate). The percentage of dimensional change
      ranged from -0.496 to 0.161 percent for the extended-pour alginate and from 
      0.174 to 0.912 percent for the conventional alginate. CONCLUSIONS: Results of
      analysis of variance and paired t tests indicated that when generated immediately
      and at day 5, casts produced from both impression materials were not
      statistically different from the standard model (P < .05). CLINICAL IMPLICATIONS:
      When stored properly, both alginate materials can produce accurate impressions at
      day 5 for diagnostic casts and for fabrication of acrylic appliances.

PMID- 20045818
TI  - Psychological correlates of medical comorbidities in patients with
      temporomandibular disorders.
AB  - BACKGROUND: Medical comorbidities are common among patients with
      temporomandibular disorders (TMDs). The authors examined the relationship between
      the medical comorbidities in patients with TMDs and their psychological
      functioning. METHODS: The sample consisted of 1,060 adults with TMDs, of whom 85
      percent (n = 901) were female. At the time patients were evaluated at a
      university orofacial pain center, from 1997 through 2007, they completed medical
      history and psychological questionnaires. On the basis of retrospective chart
      reviews, the authors assessed the relationship between medical comorbidities and
      psychological functioning, controlling for pain severity, by using multivariate
      analyses of covariance. RESULTS: The mean total number of medical comorbidities
      was 3.49 (standard deviation [SD] = 2.87; range, 0-16). The authors found a
      linear relationship between number of medical comorbidities and overall
      psychological distress (t[1, 959] = 16.79, P < .001) and interference owing to
      pain (t[1, 1,028] = 18.03, P < .001). CONCLUSIONS: Patients with TMDs who have
      medical comorbidities may be at increased risk of experiencing poor psychological
      functioning. Further study is needed to investigate whether the observed
      relationship changes across time. CLINICAL IMPLICATIONS: The physical and
      psychological health of patients with TMDs may influence the course of their pain
      condition. When treating these patients, dentists routinely should assess not
      only the symptoms of their TMDs but also their general health status.

PMID- 20045820
TI  - Eye fixations when viewing faces.
AB  - BACKGROUND: There is disagreement in the literature about the relative importance
      of the mouth and the teeth to facial attractiveness. Few investigators use
      objective measures for quantifying which facial features are important and their
      order of importance. Objective measures of the relative importance of a facial
      feature are in what order, for how long and how often viewers look at it. The
      authors conducted a study to determine the hierarchy and length of time study
      participants spent viewing features in facial images. METHODS: The participants
      were 50 young adults. The authors used a pupillary-corneal reflection technique
      to measure viewers' eye movements when they were viewing images of faces after
      orthodontic treatment was completed. The authors took the measurements again
      after a two-week interval. They quantified eye fixations for six areas of
      interest: eyes, ears, nose, mouth, chin and other. The variables measured were
      the location of the first fixation, the location of the area of maximum fixation
      duration and the location of the area receiving the maximum number of fixations.
      RESULTS: Intraobserver variability among the participants was high for most of
      the variables assessed (kappa < 0.30). For the smile image, first fixation, the
      most frequent and the longest fixations were other, eye, nose, mouth, ear and
      chin, in that order. The mouth, even the smiling mouth, received less than 10
      percent of the viewers' visual attention. CONCLUSION: Viewers' visual fixations
      on images of well-balanced faces do not preferentially go to any single facial
      feature. The mouth attracts only a small part of visual attention in well
      balanced faces.

PMID- 20045821
TI  - Oral ulcerations in a patient with severe asthma.

PMID- 20045822
TI  - Dentists' attitudes toward chairside screening for medical conditions.
AB  - BACKGROUND: of previous studies demonstrated the effectiveness of chairside
      medical screening by dentists to identify patients at increased risk of
      experiencing cardiovascular-associated events. In this study, the authors
      assessed dentists' attitudes, willingness and perceived barriers regarding
      chairside medical screening in the dental office. METHODS: A national, random
      sample of U.S. general dentists was surveyed by mail by means of an anonymous
      questionnaire that involved a five-point Likert scale (1 = very important/very
      willing; 5 = very unimportant/very unwilling). Friedman nonparametric analysis of
      variance was used to compare response items within each question. RESULTS: Of
      1,945 respondents, most were male (82.3 percent), white (85.7 percent) and 40 to
      60 years old (59.4 percent) and had practiced for more than 10 years (84.5
      percent). The majority thought it was important for dentists to conduct screening
      for hypertension (85.8 percent), cardiovascular disease (76.8 percent), diabetes
      mellitus (76.6 percent), hepatitis (71.5 percent) and human immunodeficiency
      virus infection (68.8 percent). Respondents were willing to refer patients for
      consultation with physicians (96.4 percent), collect oral fluids for salivary
      diagnostics (87.7 percent), conduct medical screenings that yield immediate
      results (83.4 percent) and collect blood via finger stick (55.9 percent).
      Respondents were significantly more willing (P < .001) to collect saliva than
      height and weight measurements or blood via finger stick (mean ranks: 2.05, 2.96
      and 3.05, respectively). Insurance was significantly less important (P < .001)
      than time, cost, liability or patients' willingness (mean ranks: 3.51, 2.96,
      2.94, 2.83 and 2.77, respectively). CONCLUSIONS: Dentists considered medical
      screening important and were willing to incorporate it into their practices.
      Additional education and practical implementation strategies are necessary to
      address perceived barriers. CLINICAL IMPLICATIONS: The findings of this study
      regarding chairside medical screening may lead to changes in our approach to
      dental education and may help define the practice of dentistry in the future.

PMID- 20045823
TI  - The effect of air-polishing abrasives on wear of direct restoration materials and
      sealants.
AB  - BACKGROUND: Air-polishing devices (APDs) effectively remove supragingival
      staining. However, the use of APDs on restorative surfaces may result in
      clinically relevant surface damage and material loss. METHODS: The authors made
      plane specimens (N = 180) of dental restorative materials (Tetric EvoCeram
      [Ivoclar Vivadent, Schaan, Liechtenstein], Tetric Flow [Ivoclar Vivadent ],
      Grandio Flow [VOCO, Cuxhaven, Germany], Admira Seal [VOCO], Grandio Seal [VOCO])
      and Ionofil Molar [VOCO]). The authors treated the specimens with standardized
      air abrasion, using three abrasives (Acclean Air Preventive Powder [Henry Schein,
      Langen, Germany], AirFlow Prophylaxis Powder [EMS, Nyon, Switzerland] and ClinPro
      Prophy Powder [3M ESPE, Seefeld, Germany]) for 10 seconds each. The authors used
      profilometric scanning to quantify defect depth and volume loss. RESULTS: The
      abrasive ClinPro Prophy Powder produced the smallest defect depth and volume
      loss. Tetric EvoCeram experienced the smallest defect depth, whereas the flowable
      composites showed the greatest defect depths and volume losses. Sealants showed
      defects comparable with those the authors found in the glass ionomer, which were
      significantly smaller than those found in flowable composites. CONCLUSIONS: Air
      polishing of sealants and restorative materials always results in substance loss
      and surface damage. The sealants performed better in terms of abrasion resistance
      than did the flowable composites tested. Among the air-polishing abrasives,
      ClinPro Prophy Powder caused the least abrasive damage. CLINICAL IMPLICATIONS:
      Clinicians should use low-abrasion powder for frequent cleaning of discolored
      restorations with APDs to avoid excessive abrasion of restorative materials.

PMID- 20045824
TI  - Evaluating factors that affect the shade-matching ability of dentists, dental
      staff members and laypeople.
AB  - BACKGROUND: The authors conducted a study to evaluate the influence of dentists'
      and nondentists' experience, age, sex, eye color and use of eyeglasses or contact
      lenses on tooth shade-matching ability. METHODS: The authors included 120
      participants in this study conducted in Istanbul (periodontists, oral and
      maxillofacial surgeons, orthodontists, endodontists, pediatric dentists,
      prosthodontists, restorative dentists, general dentists in private practice,
      dental technicians, dental assistants, dental assistant students and laypeople).
      The authors assigned participants to one of three groups: group 1 was composed of
      prosthodontists, restorative dentists and dental technicians; group 2 consisted
      of other dental specialists and general dentists; and group 3 included dental
      assistants, dental assistant students and laypeople. The authors asked
      participants to match the shades of three artificial maxillary right central
      incisors (Vitapan acrylic teeth [shades 2L1.5, 1M2, 2R1.5], Vita Zahnfabrik, Bad
      Sackingen, Germany) by using a shade guide system (Vita Toothguide 3D-Master,
      Vita Zahnfabrik). They calculated shade matching for the three color components
      (value, hue, chroma) and analyzed the results by using a chi(2) test. RESULTS:
      The rate of success in matching the shade for IM2 was 53.3 percent for
      participants in group 1, 30 percent for participants in group 2 and 20 percent
      for participants in group 3 (P = .017). However, there were no significant
      differences between the three groups for shades 2L1.5 and 2R1.5. Professional
      experience (P = .003) and age (P = .027) were associated with shade-matching
      success for tooth shade 2L1.5 only. The results showed no statistically
      significant differences with respect to sex, eye color or use of eyeglasses or
      contact lenses. CONCLUSIONS: Dental care professionals who routinely performed
      restorative procedures matched the shades better than did participants in other
      groups. Professional experience was associated positively with the outcome, while
      sex, eye color and use of eyeglasses or contact lenses did not have any effect on
      shade-matching results. CLINICAL IMPLICATIONS: To improve shade-matching skills,
      clinicians should participate in hands-on courses, continuing education classes
      and other training programs.

PMID- 20045825
TI  - Evidence indicates minimal short-term space loss after premature loss of primary
      first molars.

PMID- 20045828
TI  - Too much tooth, not enough tooth: making decisions about anterior tooth position.

PMID- 20045826
TI  - Dental care needs, use and expenditures among U.S. children with and without
      special health care needs.
AB  - BACKGROUND: Controversy exists in the literature about whether dental care needs,
      use and expenditures differ between children with and without special health care
      needs (SHCN). METHODS: The authors used data from the 2005 Medical Expenditure
      Panel Survey (MEPS) for children younger than 18 years. The MEPS questionnaire
      included the Children with Special Health Care Needs Screener, which defines a
      child as having SHCN if he or she meets at least one of five specific criteria.
      Using bivariate and multivariable regression analyses, the authors evaluated the
      effect of SHCN on unmet dental care needs, type of dental care received and
      average dental care expenditures. RESULTS: Children with special health care
      needs (CSHCN) had an adjusted odds ratio (AOR) of 1.49 (95 percent confidence
      interval [CI] = 1.09-2.05) of having unmet dental care needs compared with
      children without SHCN, and CSHCN who met four or five screener criteria had an
      AOR of 2.2 (95 percent CI = 1.16-4.20). CSHCN used more dental care services and
      were more likely to receive only nonpreventive care. Average dental care
      expenditures were not statistically different between CSHCN and children without
      SHCN, and there was variability among CSHCN in unmet dental care needs and use.
      CONCLUSIONS: Unmet dental care needs are associated independently with SHCN
      status and complexity (based on the number of screener criteria the child met).
      The CSHCN populations in MEPS varied in their ability to obtain and use needed
      dental care services. Practice Implications. It is important to consider the
      diversity of CSHCN when developing systems of dental care for this population.

PMID- 20045829
TI  - Managing staff conflict.

PMID- 20045830
TI  - Is it ethical to claim full credit for an on-site continuing education course
      that the presenter shortens significantly?

PMID- 20045831
TI  - Punch resection alaplasty technique in dogs and cats with stenotic nares: 14
      cases.
AB  - Punch resection alaplasty is a previously unreported surgical technique for the
      management of stenotic nares. Nine dogs underwent the procedure in conjunction
      with soft palate resection and/or laryngeal sacculectomy. Three dogs and two cats
      were treated with the novel punch resection alaplasty technique alone.
      Symmetrical resection was achieved, providing excellent cosmesis. Good to
      excellent results were achieved in all cases, with owners feeling that their
      pet's overall well being was improved following surgery.

PMID- 20045832
TI  - Primary immune-mediated thrombocytopenia in cats.
AB  - Feline primary immune-mediated thrombocytopenia (pIMT) is a rare condition, and
      only a few cases have been described in veterinary literature. Five cats with
      severe thrombocytopenia most likely due to pIMT are described. A flow cytometry
      platelet-bound antibody test was positive in all cats; underlying diseases or
      triggering factors causing thrombocytopenia were not detected. Three cats were
      transfused with blood type-compatible fresh whole blood; one cat received
      Oxyglobin as well. All cats were treated with prednisolone; one cat received
      chlorambucil in addition. Four cats responded to treatment and were discharged
      from the hospital. One cat was euthanized due to dyspnea. Primary immune-mediated
      thrombocytopenia is rarely diagnosed in cats, but it is important as a
      differential diagnosis in cats presented with surface bleeding.

PMID- 20045833
TI  - Multiple distinct malignancies in dogs: 53 cases.
AB  - Despite the clinical recognition of multiple distinct types of neoplasia in
      individual dogs, a detailed description of such cases has not recently been
      published. Canine oncology cases that were diagnosed with multiple, confirmed,
      distinct malignancies were prospectively collected for analysis. Approximately 3%
      of 1722 dogs that were presented to the oncology service at the Colorado State
      University Veterinary Medical Center were diagnosed with multiple distinct
      primary tumors. No significant breed or sex predisposition was apparent. Dogs
      with mast cell tumor, malignant melanoma, and thyroid carcinoma were
      significantly overrepresented and thus more likely to be diagnosed with multiple
      tumor types. These findings emphasize the importance of thorough, whole-body
      evaluation for dogs presented with mast cell tumor, malignant melanoma, and
      thyroid carcinoma. Furthermore, because approximately 33% of dogs that were
      presented with thyroid tumors were found to have additional distinct tumors,
      complete staging is justified in all dogs presented with thyroid tumors.

PMID- 20045834
TI  - Transvenous heartworm extraction in a ferret with caval syndrome.
AB  - A 10-month-old ferret was diagnosed with heartworm disease and caval syndrome.
      Associated clinical signs included weakness and a green-colored urine, identified
      as biliverdinuria. Despite the animal's small size, removal of three heartworms
      via transvenous heartworm extraction was successfully performed. Although at
      least one female worm remained in the right ventricle, the majority of clinical
      signs related to the presence of the heartworms resolved. The ferret was
      subsequently managed medically with corticosteroids and monthly heartworm
      prevention. This case documents the presence of biliverdinuria associated with
      caval syndrome and successful transvenous heartworm extraction in a ferret.

PMID- 20045835
TI  - Adrenal pheochromocytoma with contralateral adrenocortical adenoma in a cat.
AB  - A 7-year-old, neutered male cat was presented with a 6-month history of
      progressive polyuria, polydipsia, polyphagia, aggression, and weight gain.
      Previous blood work, urinalysis, and radiographs did not delineate a cause for
      the clinical signs. An ultrasound revealed bilateral adrenal gland enlargement. A
      low-dose dexamethasone suppression test was consistent with hyperadrenocorticism.
      Based on these findings, bilateral adrenalectomy was attempted and successfully
      performed. Histopathology was consistent with a cortical adenoma in the right
      adrenal gland and a pheochromocytoma in the left adrenal gland. This association
      has never been reported in the cat.

PMID- 20045836
TI  - Confirmed 2,4-dichlorophenoxyacetic acid toxicosis in a dog.
AB  - A 2-year-old, intact male Weimaraner was evaluated for episodic extensor rigidity
      and a stiff gait of 24 hours' duration. Percussion of the proximal appendicular
      muscles with a reflex hammer resulted in formation of dimples consistent with
      myotonia. Electromyography identified myotonic potentials. Residues of 2,4
      dichlorophenoxyacetic acid (2,4-D) were detected in both serum and urine. The dog
      was treated with intravenous fluid therapy for 36 hours, and clinical signs
      improved dramatically. Toxicosis with 2,4-D should be considered a differential
      for acquired myotonia in dogs with or without systemic signs. Exposed dogs with
      only clinical signs of myotonia can have good clinical outcomes. A confirmed
      clinical case of 2,4-D toxicosis in the dog has not previously been reported.

PMID- 20045837
TI  - Elevated cardiac troponin I in a dog with an intracranial meningioma and evidence
      of myocardial necrosis.
AB  - A 10-year-old, spayed female Weimaraner was referred for an acute onset of
      generalized tremors, seizures, and obtundation. Neurological examination revealed
      severe obtundation and a right-sided menace response deficit. Neuroanatomical
      diagnosis was consistent with a left prosencephalic lesion. The serum cardiac
      troponin I level was high, indicative of acute myocardial necrosis. With magnetic
      resonance imaging, a mass was observed in the left olfactory bulb and tract, with
      extensive edema in the white matter of the left cerebrum. The hippocampus was
      hyperintense on T2-weighted and T2-weighted fluid-attenuated inversion recovery
      images. At necropsy, a meningioma of the left olfactory bulb and ischemic cell
      change in the neurons of the hippocampus were identified. In the heart,
      microscopic lesions consistent with myocardial necrosis were observed. This is
      the first case to document an elevated cardiac troponin I level in a dog with
      intracranial disease and myocardial necrosis.

PMID- 20045838
TI  - Long-retained vaginal foreign body causing chronic vaginitis in a bulldog.
AB  - A vaginal foreign body consisting of a piece of retained calvarium from a
      macerated fetus was identified and removed using vaginoscopy in a 4-year-old,
      spayed female bulldog. The dog had a 12-month history of chronic mucopurulent
      vaginitis. Vaginal foreign bodies, although uncommon, are a differential
      diagnosis for recurrent mucopurulent or hemorrhagic chronic vaginal discharge. A
      case of chronic vaginitis caused by a long-retained intravaginal foreign body in
      a dog is described and compared to four other canine cases reported in the
      literature.

PMID- 20045839
TI  - Arrhythmias and elevated troponin I in a dog with steroid-responsive meningitis
      arteritis.
AB  - A 10-month-old dog was presented with clinical signs of fever, lethargy,
      inappetence, and cardiac arrhythmias. Computed tomography scan and cerebrospinal
      fluid analysis supported the diagnosis of steroid-responsive meningitis
      arteritis. Echocardiography, electrocardiogram, and elevated serum troponin I
      supported a diagnosis of myocarditis. The arrhythmias resolved during treatment
      of the primary neurological disease, and they were considered as secondary to the
      meningitis.

PMID- 20045840
TI  - Carboplatin chemotherapy in a cat with a recurrent anal sac apocrine gland
      adenocarcinoma.
AB  - An 8-year-old, castrated male, domestic shorthaired cat was presented for
      evaluation of a perianal mass. The mass was incompletely excised, and
      histological assessment resulted in a diagnosis of anal sac adenocarcinoma. The
      cat had a partial response to carboplatin therapy but a short overall duration of
      response. Necropsy confirmed the original diagnosis as well as metastasis to the
      regional lymph nodes and lungs.

PMID- 20045841
TI  - AAFP-AAHA: Feline life stage guidelines.

PMID- 20045843
TI  - A resolution for 2010: ring in the true.

PMID- 20045845
TI  - Monitor alarm fatigue: standardizing use of physiological monitors and decreasing
      nuisance alarms.
AB  - BACKGROUND: Reliance on physiological monitors to continuously "watch" patients
      and to alert the nurse when a serious rhythm problem occurs is standard practice
      on monitored units. Alarms are intended to alert clinicians to deviations from a
      predetermined "normal" status. However, alarm fatigue may occur when the sheer
      number of monitor alarms overwhelms clinicians, possibly leading to alarms being
      disabled, silenced, or ignored. PURPOSE: Excessive numbers of monitor alarms and
      fear that nurses have become desensitized to these alarms was the impetus for a
      unit-based quality improvement project. METHODS: Small tests of change to improve
      alarm management were conducted on a medical progressive care unit. The types and
      frequency of monitor alarms in the unit were assessed. Nurses were trained to
      individualize patients' alarm parameter limits and levels. Monitor software was
      modified to promote audibility of critical alarms. RESULTS: Critical monitor
      alarms were reduced 43% from baseline data. The reduction of alarms could be
      attributed to adjustment of monitor alarm defaults, careful assessment and
      customization of monitor alarm parameter limits and levels, and implementation of
      an interdisciplinary monitor policy. DISCUSSION: Although alarms are important
      and sometimes life-saving, they can compromise patients' safety if ignored. This
      unit-based quality improvement initiative was beneficial as a starting point for
      revamping alarm management throughout the institution.

PMID- 20045846
TI  - Monitor alarm fatigue.

PMID- 20045847
TI  - A nursing clinical decision support system and potential predictors of head-of
      bed position for patients receiving mechanical ventilation.
AB  - BACKGROUND: Patients receiving mechanical ventilation are at high risk for
      pneumonia due to aspiration. Published guidelines recommend elevating the head of
      the bed 30 degrees to 45 degrees , if not contraindicated, to reduce risk, but
      this intervention is underused. OBJECTIVES: To facilitate incorporating evidence
      based practice by improving positioning of patients receiving mechanical
      ventilation and to identify patient and nurse characteristics that predict use of
      the guideline. METHODS: A modified interrupted time-series design was used. Data
      were collected on 43 patients and 33 nurses 3 separate times in a 12-bed
      intensive care unit at a medium-sized hospital. A total of 105 observations were
      recorded for analysis each time. RESULTS: Mean elevations of the head of the bed
      increased significantly from phase 1 (27.7 degrees ) to phase 2 (31.7 degrees )
      and from phase 1 to phase 3 (31.1 degrees ). Elevations were higher for tube-fed
      patients than for patients not given enteral tube feedings. Elevations were
      higher for patients with a pulmonary-related diagnosis and lower for patients
      with a gastrointestinal diagnosis than for patients with other diagnoses.
      Elevations were lower for patients with a body mass index between 25.0 and 29.9
      (overweight) than for patients with other body mass index values. Nurse
      characteristics were not significant predictors of elevation. CONCLUSION: A
      nursing clinical decision support system integrated into a patient's electronic
      flow sheet can increase nurses' adherence to guidelines. Pulmonary and
      gastrointestinal diagnoses, body mass index, and tube feeding are predictors of
      elevation of the head of the bed.

PMID- 20045848
TI  - A comparison of methohexital versus etomidate for endotracheal intubation of
      critically ill patients.
AB  - BACKGROUND: Methohexital has been used for procedural sedation in the emergency
      department, but its use for endotracheal intubation in intensive care units has
      not been studied. OBJECTIVE: To compare methohexital with etomidate with respect
      to their effectiveness and safety of use for endotracheal intubation in the
      intensive care unit. METHODS: Retrospective, observational, single-center cohort
      study of consecutive patients admitted between December 2006 and August 2007 to a
      medical intensive care unit in a tertiary-care hospital. RESULTS: Twenty-three
      patients who received methohexital and 23 who received etomidate for endotracheal
      intubation were included. The 2 groups differed in age (mean [SD], 55 [13] vs 64
      [13] years, P = .03) but not in baseline demographics or illness severity scores.
      Mean (SD) doses given were 1 (0.2) mg/kg for methohexital and 0.2 (0.1) mg/kg for
      etomidate. Use of midazolam, fentanyl, and succinylcholine was similar between
      the groups. Rates of successful intubation after 1 attempt (78% vs 83%), time to
      successful intubation (mean, 5.9 vs 4 minutes), and number of intubation attempts
      (mean, 1.5 vs 1.2) also were similar. Change in hemodynamics (delta systolic
      blood pressure), vasopressor requirements, and amount of fluid resuscitation
      (normal saline) did not differ significantly between the groups. CONCLUSIONS:
      Rates of successful intubation are similar with etomidate and methohexital.
      Methohexital provides adequate sedation and could be an alternative to etomidate,
      although both agents were often associated with development of hypotension.
      Prospective studies are needed to establish the safety of methohexital use in
      intensive care patients.

PMID- 20045849
TI  - Reliability and validity of the face, legs, activity, cry, consolability
      behavioral tool in assessing acute pain in critically ill patients.
AB  - BACKGROUND: Few investigators have evaluated pain assessment tools in the
      critical care setting. OBJECTIVE: To evaluate the reliability and validity of the
      Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale in assessing
      pain in critically ill adults and children unable to self-report pain. METHODS:
      Three nurses simultaneously, but independently, observed and scored pain
      behaviors twice in 29 critically ill adults and 8 children: before administration
      of an analgesic or during a painful procedure, and 15 to 30 minutes after the
      administration or procedure. Two nurses used the FLACC scale, the third used
      either the Checklist of Nonverbal Pain Indicators (for adults) or the COMFORT
      scale (for children). RESULTS: For 73 observations, FLACC scores correlated
      highly with the other 2 scores (rho = 0.963 and 0.849, respectively), supporting
      criterion validity. Significant decreases in FLACC scores after analgesia (or at
      rest) supported construct validity of the tool (mean, 5.27; SD, 2.3 vs mean,
      0.52; SD, 1.1; P < .001). Exact agreement and kappa statistics, as well as
      intraclass correlation coefficients (0.67-0.95), support excellent interrater
      reliability of the tool. Internal consistency was excellent; the Cronbach alpha
      was 0.882 when all items were included. CONCLUSIONS: Although similar in content
      to other behavioral pain scales, the FLACC can be used across populations of
      patients and settings, and the scores are comparable to those of the commonly
      used 0-to-10 number rating scale.

PMID- 20045851
TI  - Asystole.

PMID- 20045850
TI  - Racial differences in women's prodromal and acute symptoms of myocardial
      infarction.
AB  - BACKGROUND: Minority women, especially black and Hispanic women, have higher
      rates of coronary heart disease and resulting disability and death than do white
      women. A lack of knowledge of minority women's symptoms of coronary heart disease
      may contribute to these disparities. OBJECTIVE: To compare black, Hispanic, and
      white women's prodromal and acute symptoms of myocardial infarction. METHODS: In
      total, 545 black, 539 white, and 186 Hispanic women without cognitive impairment
      at 15 sites were retrospectively surveyed by telephone after myocardial
      infarction. With general linear models and controls for cardiovascular risk
      factors, symptom severity and frequency were compared among racial groups.
      Logistic regression models were used to examine individual prodromal or acute
      symptoms by race, with adjustments for cardiovascular risk factors. RESULTS:
      Among the women, 96% reported prodromal symptoms. Unusual fatigue (73%) and sleep
      disturbance (50%) were the most frequent. Eighteen symptoms differed
      significantly by race (P<.01); blacks reported higher frequencies of 10 symptoms
      than did Hispanics or whites. Thirty-six percent reported prodromal chest
      discomfort; Hispanics reported more pain/discomfort symptoms than did black or
      white women. Minority women reported more acute symptoms (P < .01). The most
      frequent symptom, regardless of race, was shortness of breath (63%); 22 symptoms
      differed by race (P <.01). In total, 28% of Hispanic, 38% of black, and 42% of
      white women reported no chest pain/discomfort. CONCLUSIONS: Prodromal and acute
      symptoms of myocardial infarction differed significantly according to race.
      Racial descriptions of women's prodromal and acute symptoms should assist
      providers in interpreting women's symptoms.

PMID- 20045852
TI  - Foot-and-mouth disease viral loads in pigs in the early, acute stage of disease.
AB  - The progress and pathogenesis of foot-and-mouth disease virus (FMDV) was studied
      in infected pigs by observing the development of clinical signs in two separate
      experiments. Viral loads were determined by real-time quantitative RT-PCR in the
      liver, spleen, cervical lymph node, mandibular lymph node, retropharyngeal lymph
      node, soft palate, pharynx, tonsil, tongue and skin (coronary band area). Tissue
      samples were collected from both inoculated and contact-infected pigs at several
      time points during infection, and blood samples were collected to assess viraemia
      and its relationship to tissue viral load. Virus first appeared in the lymph
      nodes, followed by viraemia and then clinical signs. The results suggested that
      FMDV accumulated in lymphoid tissue up to six hours after infection, in the
      tissues drained by the mandibular lymph node and tonsil and then disseminated
      throughout the body where epithelial cells were the favoured sites of
      replication.

PMID- 20045853
TI  - Biochemical constituents of peritoneal fluid in cows.
AB  - Samples of peritoneal fluid and jugular venous blood were taken simultaneously
      from 95 clinically healthy Holstein-Friesian cows. The concentrations of total
      protein, albumin, glucose, cholesterol, fibrinogen, L-lactate and D-dimer, the
      activities of lactate dehydrogenase (LDH), alkaline phosphatase and creatine
      kinase, and the white blood cell count were determined in the samples. Light's
      criteria, the serum-ascites albumin gradient (SAAG) and the ratios of the
      concentration of each parameter in peritoneal fluid to its concentration in blood
      were calculated. The mean concentrations of total protein, albumin and D-dimer,
      the activity of LDH and the SAAG were different from the reference values for
      monogastric animals and human beings.

PMID- 20045854
TI  - Measurement of serum acute phase proteins to monitor postoperative recovery in
      anoestrous bitches after ovariohysterectomy.
AB  - Six healthy bitches underwent ovariohysterectomy, performed by medial laparotomy
      according to routine methods. Blood samples were taken by venepuncture just
      before and 24, 48 and 72 hours and seven days after surgery. The serum C-reactive
      protein (CRP) (P<0.001), haptoglobin (P<0.001) and caeruloplasmin (P<0.05) levels
      were all significantly higher in the postoperative period than in the samples
      taken before surgery. The CRP levels increased rapidly and dramatically, while
      the levels of haptoglobin and caeruloplasmin rose more gradually.

PMID- 20045855
TI  - Antibodies to influenza and West Nile viruses in horses in Mexico.

PMID- 20045856
TI  - Isolation of a virus related to canine parvovirus type 2 from a raccoon (Procyon
      lotor).

PMID- 20045858
TI  - Ergot poisoning of water buffaloes in the UK.

PMID- 20045859
TI  - Clinical governance.

PMID- 20045860
TI  - Changes to the BVA/KC Canine Health Schemes.

PMID- 20045861
TI  - Congenital goitre and alopecia in pedigree Saler cattle.

PMID- 20045862
TI  - Hepatitis E virus in retail pig livers.

PMID- 20045863
TI  - Electrical storm induced by H1N1 A influenza infection.
AB  - Pandemic H1N1 influenza A virus is spreading worldwide. We report a case of
      electrical storm during H1N1 influenza A infection in a patient with congenital
      long-QT syndrome (LQTS) that was previously stable on beta-blocker therapy.
      Possible causes for the association of A flu and LQTS recurrent ventricular
      arrhythmias are discussed.

PMID- 20045864
TI  - Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia
      inducibility in subjects with Brugada ECG phenotype.

PMID- 20045865
TI  - Selective slow pathway ablation using transseptal approach in a patient with
      surgically corrected partial atrioventricular canal defect and atrioventricular
      nodal reentrant tachycardia of the common type.
AB  - A 26-year-old woman with partial atrioventricular (AV) canal defect surgically
      closed with pericardial patch in a mode that the triangle of Koch had become part
      of the left atrium underwent successful slow pathway ablation for slow-fast AV
      nodal reentrant tachycardia. Transseptal approach was used because of the
      atypical post-operative anatomy. Transseptal catheter ablation of the slow
      pathway can be a reasonable and safe alternative in patients subjected to this
      type of operation.

PMID- 20045866
TI  - Pitavastatin decreases the expression of endothelial lipase both in vitro and in
      vivo.
AB  - AIMS: In addition to their cholesterol-lowering effect, statins increase high
      density lipoprotein cholesterol (HDL-C) levels. Endothelial lipase (EL) is a
      regulator of plasma HDL-C levels. In the present study, the effects of statins on
      EL expression were investigated. METHODS AND RESULTS: The 3-hydroxy-3
      methylglutaryl-coenzyme A reductase inhibitor pitavastatin suppressed basal and
      cytokine-treated EL expression in endothelial cells. Concomitant treatment with
      mevalonate or geranylgeranyl pyrophosphate completely reversed the inhibitory
      effect of pitavastatin, suggesting that geranylgeranylated proteins are involved
      in the inhibition of EL expression by statins. Inhibition of RhoA activity by
      overexpression of a dominant-negative mutant of RhoA or a Rho kinase inhibitor
      decreased EL levels. Pitavastatin reduced phospholipase activities of endothelial
      cells, and concomitant treatment with mevalonate reversed its inhibitory effect.
      Pitavastatin reduced RhoA activity and EL expression in mouse tissues.
      Furthermore, plasma EL concentrations in human subjects were measured by enzyme
      linked immunosorbent assays. Plasma EL levels were negatively associated with
      plasma HDL levels in 237 patients with cardiovascular diseases, and pitavastatin
      treatment reduced plasma EL levels and increased HDL-C levels in 48 patients with
      hypercholesterolaemia. CONCLUSION: These findings suggest that statins can reduce
      EL expression in vitro and in vivo via inhibition of RhoA activity. The
      inhibition of EL expression in the vessel wall may contribute to the anti
      atherogenic effects of statins.

PMID- 20045867
TI  - Pregnancy outcome in patients with complex pulmonary atresia: case report and
      review of the literature.
AB  - Pulmonary atresia, a rare and complex congenital heart disease, is characterized
      by the absence of the central pulmonary artery and by the presence of a
      ventricular septal defect and aortopulmonary collaterals. Pregnancy reports
      concerning maternal and offspring outcome after palliative operation or repaired
      pulmonary atresia are sparse. We report here on the outcome of pregnancy in a
      woman, aged 36, with complex pulmonary atresia in whom palliative operation had
      been performed at the age of 23. We review the medical literature on pregnancy
      course as well as maternal and foetal outcome in cases involving this maternal
      congenital heart disease.

PMID- 20045869
TI  - ITPKC gene SNP rs28493229 and Kawasaki disease in Taiwanese children.
AB  - Kawasaki disease (KD) is a systemic vasculitis caused by unknown infectious
      agents, host immune dysregulation and genetic susceptibility in children.
      Coronary artery lesions (CALs) complicate 15-25% of cases of untreated KD. The
      aim of this study was to investigate if the single-nucleotide polymorphism (SNP)
      rs28493229 of the ITPKC gene is associated with susceptibility to KD or with CALs
      in Taiwanese children. A total of 385 unrelated Taiwanese children (222 boys and
      163 girls) with KD were included, 140 of whom had CALs. Mean age at diagnosis was
      1.9 +/- 1.7 (0.1-10.2) years. Rs28493229 was genotyped in children with KD and
      1158 ethnically matched healthy controls using the TaqMan Allelic Discrimination
      Assay. In 184 families with KD, both biological parents were available,
      constituting 184 trios with their children. They were assessed in a family-based
      study by means of a transmission/disequilibrium test (TDT). No significant
      differences in genotype (P = 0.29 and P = 0.29, respectively), allele (P = 0.14
      and P = 0.22, respectively) and carrier (P = 0.22 and P = 0.25, respectively)
      frequencies of the SNP were found between healthy controls and children with KD
      or those with CALs. TDT in the 184 family trios and in 69 trios where the child
      had CALs did not reveal significant overtransmittion of the C allele. In
      conclusion, we did not find a statistically significant association between the
      ITPKC gene SNP rs28493229 and KD or CALs in Taiwanese children.

PMID- 20045868
TI  - Myosin binding protein C1: a novel gene for autosomal dominant distal
      arthrogryposis type 1.
AB  - Distal arthrogryposis type I (DA1) is a disorder characterized by congenital
      contractures of the hands and feet for which few genes have been identified. Here
      we describe a five-generation family with DA1 segregating as an autosomal
      dominant disorder with complete penetrance. Genome-wide linkage analysis using
      Affymetrix GeneChip Mapping 10K data from 12 affected members of this family
      revealed a multipoint LOD(max) of 3.27 on chromosome 12q. Sequencing of the slow
      twitch skeletal muscle myosin binding protein C1 (MYBPC1), located within the
      linkage interval, revealed a missense mutation (c.706T>C) that segregated with
      disease in this family and causes a W236R amino acid substitution. A second
      MYBPC1 missense mutation was identified (c.2566T>C)(Y856H) in another family with
      DA1, accounting for an MYBPC1 mutation frequency of 13% (two of 15). Skeletal
      muscle biopsies from affected patients showed type I (slow-twitch) fibers were
      smaller than type II fibers. Expression of a green fluorescent protein (GFP)
      tagged MYBPC1 construct containing WT and DA1 mutations in mouse skeletal muscle
      revealed robust sarcomeric localization. In contrast, a more diffuse localization
      was seen when non-fused GFP and MYBPC1 proteins containing corresponding MYBPC3
      amino acid substitutions (R326Q, E334K) that cause hypertrophic cardiomyopathy
      were expressed. These findings reveal that the MYBPC1 is a novel gene responsible
      for DA1, though the mechanism of disease may differ from how some cardiac MYBPC3
      mutations cause hypertrophic cardiomyopathy.

PMID- 20045870
TI  - Season-associated modifications in symplasmic organization of the cambium in
      Populus nigra.
AB  - BACKGROUND AND AIMS: Alterations of plasmodesma (PD) connectivity are likely to
      be very important for plant development. Here, the repetitive division pattern of
      cambial initials in Populus nigra 'italica' was studied to follow the development
      of the PD network during maturation. Furthermore, seasonal changes were
      investigated in order to trace indications for developmental and functional
      adaptations. METHODS: Cambium samples of P. nigra twigs, collected in summer,
      autumn and spring, were chemically fixed for transmission electron microscopy.
      The parameters, PD density (number of PDs per square micrometre cell-wall area)
      and PD frequency (total number of PDs per average cell-wall area), were
      determined for radial and tangential cell interfaces deposited in chronological
      order. KEY RESULTS: Data sets, presented in plasmodesmograms, show a strong
      variability in the PD network throughout the year. In summer, high PD numbers
      occur at the division wall which, after PD doubling by longitudinal fission,
      decline with further development both at the xylem and the phloem side. In
      autumn, the number of PDs at the division wall is low as they are in subsequent
      tangential interfaces. In spring, the first cell division coincides with a
      massive increase in PD numbers, in particular at the division wall. Only the
      radial walls between initials maintain their PD equipment throughout the year.
      This feature can be exploited for identification of the initial layer.
      CONCLUSIONS: PD networks in the cambium go through a strict developmental
      programme depending on the season, which is associated with changing functional
      requirements. For instance, PD numbers correlate with proliferative activity and
      potential pathways for intercellular signalling. Increases in PD numbers are
      ascribed to longitudinal fission as a major mechanism, whereas the decline in
      older derivatives is ascribed to PD degradation.

PMID- 20045871
TI  - Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in
      men.
AB  - BACKGROUND: Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule
      of disuse-induced skeletal muscle atrophy. However, few studies have carefully
      investigated whether similar pathways are modulated with physical activity and
      age. METHODS: The present study examined lean mass, maximal force production, and
      skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N =
      13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or
      young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the
      vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta
      subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated
      inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits
      p50 and p65. RESULTS: When compared with YS, OS demonstrated age-related muscle
      atrophy and reduced isokinetic knee extension torque. Physical activity in older
      individuals preserved maximal isokinetic knee extension torque. OS muscle
      contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore,
      nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not
      differ from either of the other two groups for nuclear p50 or for mRNA expression
      of IKKbeta. CONCLUSIONS: These results indicate that skeletal muscle content of
      nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound
      p65 appears to be at least partially due to significant increases in pIKBalpha. A
      sedentary lifestyle appears to play some role in increased IKBalpha; however,
      further research is needed to identify downstream effects of this increase.

PMID- 20045873
TI  - Improvement in personal meaning mediates the effects of a life review
      intervention on depressive symptoms in a randomized controlled trial.
AB  - PURPOSE: The purpose of the study was to assess the impact of a life review
      intervention on personal meaning in life and the mediating effect of personal
      meaning on depressive symptoms as the primary outcome of this form of indicated
      prevention. DESIGN AND METHODS: A multicenter randomized controlled trial was
      conducted with one group of older adults obtaining life review (N = 83) and the
      other watching a video about the art of growing older (N = 88). Measurements took
      place before and after the intervention as well as 6 months later at follow-up.
      RESULTS: It was found that those who followed life review improved more in
      personal meaning than those in the control group, although at follow-up the
      difference was no longer significant. Improvements in meaning during the
      intervention predicted decreases in depressive symptoms later in time and
      mediated the effects of the program on depressive symptoms. IMPLICATIONS:
      Personal meaning is an important asset in contemporary society, which some older
      adults find difficult to achieve. The findings from this study show that it is
      possible to support older persons in their search for meaning by means of life
      review and that this helps in alleviating depressive symptoms.

PMID- 20045875
TI  - Where perception meets memory: a review of repetition priming in visual search
      tasks.
AB  - What we have recently seen and attended to strongly influences how we
      subsequently allocate visual attention. A clear example is how repeated
      presentation of an object's features or location in visual search tasks
      facilitates subsequent detection or identification of that item, a phenomenon
      known as priming. Here, we review a large body of results from priming studies
      that suggest that a short-term implicit memory system guides our attention to
      recently viewed items. The nature of this memory system and the processing level
      at which visual priming occurs are still debated. Priming might be due to
      activity modulations of low-level areas coding simple stimulus characteristics or
      to higher level episodic memory representations of whole objects or visual
      scenes. Indeed, recent evidence indicates that only minor changes to the stimuli
      used in priming studies may alter the processing level at which priming occurs.
      We also review recent behavioral, neuropsychological, and neurophysiological
      evidence that indicates that the priming patterns are reflected in activity
      modulations at multiple sites along the visual pathways. We furthermore suggest
      that studies of priming in visual search may potentially shed important light on
      the nature of cortical visual representations. Our conclusion is that priming
      occurs at many different levels of the perceptual hierarchy, reflecting activity
      modulations ranging from lower to higher levels, depending on the stimulus, task,
      and context-in fact, the neural loci that are involved in the analysis of the
      stimuli for which priming effects are seen.

PMID- 20045872
TI  - Effect of age on the processing and import of matrix-destined mitochondrial
      proteins in skeletal muscle.
AB  - Deregulation of muscle mitochondrial biogenesis may explain the altered
      mitochondrial properties associated with aging. Maintenance of the mitochondrial
      network requires the continuous incorporation of nascent proteins into their
      subcompartments via the protein import pathway. We examined whether this pathway
      was impaired in muscle of aged animals, focusing on the subsarcolemmal and
      intermyofibrillar mitochondrial populations. Our results indicate that the import
      of proteins into the mitochondrial matrix was unaltered with age. Interestingly,
      import assays supplemented with the cytosolic fraction illustrated an attenuation
      of protein import, and this effect was similar between age groups. We observed a
      2.5-fold increase in protein degradation in the presence of the cytosolic
      fraction obtained from aged animals. Thus, the reduction of mitochondrial content
      and/or function observed with aging may not rely on altered activity of the
      import pathway but rather on the availability of preproteins that are susceptible
      to elevated rates of degradation by cytosolic factors.

PMID- 20045876
TI  - Modeling filling-in of afterimages.
AB  - Van Lier, Vergeer, and Anstis (2009) reported that color information in a visual
      afterimage could spread across regions that were not colored in the inducing
      stimulus. The perceived color and shape of the afterimage could be manipulated by
      drawn contours that apparently trap the spread of afterimage color signals. They
      further hypothesized that the observed effects indicated a common mechanism for
      afterimage color filling-in and real-color filling-in phenomena. New simulations
      of the existing boundary contour system/feature contour system model of visual
      perception (Grossberg & Mingolla, 1985a, 1985b) demonstrate the connection
      between these phenomena.

PMID- 20045877
TI  - Intact spatial updating with severely degraded vision.
AB  - Critical to low-vision navigation are the abilities to recover scale and update a
      3-D representation of space. In order to investigate whether these abilities are
      present under low-vision conditions, we employed the triangulation task of eyes
      closed indirect walking to previously viewed targets on the ground. This task
      requires that the observer continually update the location of the target without
      any further visual feedback of his/her movement or the target's location.
      Normally sighted participants were tested monocularly in a degraded vision
      condition and a normal vision condition on both indirect and direct walking to
      previously viewed targets. Surprisingly, we found no difference in walked
      distances between the degraded and normal vision conditions. Our results provide
      evidence for intact spatial updating even under severely degraded vision
      conditions, indicating that participants can recover scale and update a 3-D
      representation of space under simulated low vision.

PMID- 20045878
TI  - Reflexive orienting to gaze is not luminance dependent.
AB  - In the investigation of reflexive orienting to cues, two major theories have
      emerged: One proposes that transients created by the cue trigger attentional
      shifts, whereas the other argues that object changes are responsible for
      instigating orienting. In the present study, we examined whether luminance
      transients produced by the cue can generate reflexive orienting to gaze. Using a
      temporal order judgment paradigm under luminant or subjectively equiluminant
      conditions, participants judged which of two peripheral targets onset first. An
      uninformative gaze cue served to reflexively shift attention toward one object
      location, thereby temporally prioritizing the target presented there. The results
      revealed that attention was successfully shifted toward the cued object, as was
      evidenced by the participants' selecting the cued object as appearing first
      significantly more often than the uncued object, even when the two onset
      simultaneously. Critically, the results were comparable across luminance
      conditions. Our findings reveal that luminance transients are not necessary for
      triggering orienting to gaze cues. We suggest that the orienting observed here
      can be better explained via an object-based hypothesis whereby object changes,
      not transients, trigger reflexive orienting.

PMID- 20045879
TI  - Competition between color salience and perceptual load during visual selection
      can be biased by top-down set.
AB  - Visual salience and perceptual load may both influence the efficiency of visual
      selection. Recently, Gibson and Bryant (2008) showed that perceptual load can
      dominate color salience in a distractor interference paradigm. The purpose of the
      present study was to investigate the possibility that knowledge (of color or
      load) may modulate the relative operation of these two mechanisms. Consistent
      with previous findings, perceptual load dominated color salience, but only in
      certain contexts in which display load was mixed and high-load displays preceded
      other high-load displays. More important, color salience dominated perceptual
      load in other contexts in which display load was mixed and low-load displays
      preceded high-load displays. In addition, color salience also dominated
      perceptual load in contexts in which display load was fixed and advance knowledge
      of load was available. Altogether, the present findings suggest that the
      competition between color salience and perceptual load can vary as a function of
      task context, thereby supporting top-down accounts, although the precise aspect
      of task context remains to be identified.

PMID- 20045880
TI  - Word cues affect detection but not localization responses.
AB  - Many theories assume that pre-knowledge of an upcoming target helps visual
      selection. In those theories, a top-down set can alter the salience of the
      target, such that attention can be deployed to the target more efficiently and
      responses are faster. Evidence for this account stems from visual search studies
      in which the identity of the upcoming target is cued in advance. In five
      experiments, we show that top-down knowledge affects the speed with which a
      singleton target can be detected but not the speed with which it can be
      localized. Furthermore, we show that these results are independent of the mode of
      responding (manual or saccadic) and are not due to a ceiling effect. Our results
      suggest that in singleton search, top-down information does not affect visual
      selection but most likely does affect response selection. We argue that such an
      effect is found only when information from different dimensions needs to be
      integrated to generate a response and that this is the case in singleton
      detection tasks but not in other singleton search tasks.

PMID- 20045881
TI  - Inhibition of return in static but not necessarily in dynamic search.
AB  - If and when search involves the serial inspection of items by covert or overt
      attention, its efficiency would be enhanced by a mechanism that would discourage
      re-inspections of items or regions of the display that had already been examined.
      Klein (1988, 2000; Klein & Dukewich, 2006) proposed that inhibition of return
      (IOR) might be such a mechanism. The present experiments explored this proposal
      by combining a dynamic search task (Horowitz & Wolfe, 1998, 2003) with a probe
      detection task. IOR was observed when search was most efficient (static and
      slower dynamic search). IOR was not observed when search performance was less
      efficient (fast dynamic search).These findings are consistent with the "foraging
      facilitator" proposal of IOR and are unpredicted by theories of search that
      assume parallel accumulation of information across the array (plus noise) as a
      general explanation for the effect of set size upon search performance.

PMID- 20045882
TI  - Objects with reduced visibility still contribute to size averaging.
AB  - People can rapidly judge the average size of a collection of objects with
      considerable accuracy. In this study, we tested whether this size-averaging
      process relies on relatively early object representations or on later object
      representations that have undergone iterative processing. We asked participants
      to judge the average size of a set of circles and, in some conditions, presented
      two additional circles that were either smaller or larger than the average. The
      additional circles were surrounded by four-dot masks that either lingered longer
      than the circle array, preventing further processing with object substitution
      masking (OSM), or disappeared simultaneously with the circle array, allowing the
      circle representation to reach later visual processing stages. Surprisingly,
      estimation of average circle size was modulated by both visible circles and
      circles whose visibility was impaired by OSM. There was also no correlation
      across participants between the influence of the masked circles and
      susceptibility to OSM. These findings suggest that relatively early
      representations of objects can contribute to the size-averaging process despite
      their reduced visibility.

PMID- 20045883
TI  - Visual orienting in dynamic broadband (1/f) noise sequences.
AB  - Visual orienting has typically been characterized using simple displays--for
      example, displays with a static target placed on a homogeneous background. In the
      present study, visual orienting was investigated using a dynamic broadband (1/f)
      noise display that should mimic a more naturalistic setting and that should allow
      saccadic orienting experiments to be performed with fewer constraints. In
      Experiment 1, it was shown that the noise movie contains gaze-attracting features
      that are almost as distinct as the ones measured for (static) real-word scenes.
      The movie can therefore serve as a strong distractor. In Experiment 2, observers
      carried out a luminance target search that showed that saccadic amplitude errors
      were substantially higher (18%) than the ones measured in simple displays. That
      error is certainly one of the primary factors making gaze-fixation prediction in
      complex scenes difficult. Supplemental figures for this study may be downloaded
      from http://app.psychonomic-journals.org/content/supplemental.

PMID- 20045884
TI  - Eye movement trajectories in active visual search: contributions of attention,
      memory, and scene boundaries to pattern formation.
AB  - We relate the roles of attention, memory, and spatial constraints to pattern
      formation in eye movement trajectories previously measured in a conjunctive
      visual search task. Autocorrelations and power spectra of saccade direction
      cosines confirm a bias to progress forwardly, while turning at the display
      boundaries, plus a long-range memory component for the search path. Analyses of
      certain measures of circulation and imbalance in the eye trajectories, and their
      relations with the display area correspondingly subtended, bear signatures of
      spiraling or circulating patterns. We interpret their prevalence as mainly due to
      the interactions between three basic psychoneural mechanisms (conspicuity area,
      forward bias, long-range memory) and two task-specific geometric-spatial
      constraints on the eye trajectories (central start and display confinement).
      Conversely, computer simulations of random walks in which all psychoneural
      mechanisms are eliminated, while geometric-spatial constraints are maintained,
      show no prevalence of circulating patterns by those measures. We did find certain
      peculiarities of some individual participants in their pattern selections, but
      they appear too casual and incidental to suggest more systematic or complex
      search strategies in our randomized displays of uninformative stimuli.

PMID- 20045885
TI  - Temporal dynamics of unimodal and multimodal feature binding.
AB  - In two experiments, we studied the temporal dynamics of feature integration with
      auditory (Experiment 1) and audiovisual (Experiment 2) stimuli and manual
      responses. Consistent with previous observations, performance was better when the
      second of two consecutive stimuli shared all or none of the features of the
      first, rather than when only one of the features overlapped. Comparable partial
      overlap costs were obtained for combinations of stimulus features and responses.
      These effects decreased systematically with increasing time between the two
      stimulus-and-response events, and the decreased rate was comparable for unimodal
      and multimodal bindings. General effect size reflected the degree of task
      relevance of the dimension or modality of the respective feature, but the effects
      of relevance and of temporal delay did not interact. This suggests that the
      processing of stimuli on task-relevant sensory modalities and feature dimensions
      is facilitated by task-specific attentional sets, whereas the temporal dynamics
      might reflect that bindings "decay" or become more difficult to access over time.

PMID- 20045886
TI  - Perceiving parts and shapes from concave surfaces.
AB  - "A hole is nothing at all, but it can break your neck." In a similar fashion to
      the danger illustrated by this folk paradox, concave regions pose difficulties to
      theories of visual shape perception. We can readily identify their shapes, but
      according to principles of how observers determine part boundaries, concavities
      in a planar surface should have very different figural shapes from the ones that
      we perceive. In three experiments, we tested the hypothesis that observers
      perceive local image features differently in simulated 3-D concave and convex
      regions but use them to arrive at similar shape percepts. Stimuli were shape-from
      shading images containing regions that appeared either concave or convex in
      depth, depending on their orientation in the picture plane. The results show that
      concavities did not benefit from the same global object-based attention or
      holistic shape encoding as convexities and that the participants relied on
      separable spatial dimensions to judge figural shape in concavities. Concavities
      may exploit a secondary process for shape perception that allows regions composed
      of perceptually independent features to ultimately be perceived as gestalts.

PMID- 20045887
TI  - What causes alternations in dominance during binocular rivalry?
AB  - Several mechanisms have been proposed to account for perceptual alterations
      during binocular rivalry, including neural adaptation and neural noise. However,
      the importance of neural adaptation for producing perceptual alterations has been
      challenged in several articles (Y.-J. Kim, Grabowecky, & Suzuki, 2006; Moreno
      Bote, Rinzel, & Rubin, 2007). We devised an "online" adaptation procedure to
      reexamine the role of adaptation in binocular rivalry. Periods of adaptation
      inserted into rivalry observation periods parametrically alter the dynamics of
      rivalry such that increased adaptation duration decreases dominance duration,
      which cannot be accounted for by neural noise. Analysis of the average dominance
      durations and their variance (coefficient of variation) provides evidence for an
      increasingly important role of noise in rivalry alternations as a given dominance
      period continues in time, consistent with recent computational models.

PMID- 20045888
TI  - Emotional expression on a profile: feature height, mouth angle, and tilt.
AB  - Profiles may vary in expression with changes in the height of the profile's
      features, the mouth's angle at the profile contour, and head tilt. In three
      experiments, we varied these factors. Features low on the profile, with mouths at
      an obtuse angle to the profile line and head tilted 15 degrees forehead-forward,
      appear especially sad. High features with acute mouth angles suit forward,
      upright, and backward head tilts. Feature height, mouth angle, and head tilt on a
      profile are physical variables that can specify postures such as downcast heads
      and turned-down mouths, and thereby psychological factors. We point out
      alternative accounts of the height and tilt effects.

PMID- 20045890
TI  - The temporal distribution of information in audiovisual spoken-word
      identification.
AB  - In the present study, we examined the distribution and processing of information
      over time in auditory and visual speech as it is used in unimodal and bimodal
      word recognition. English consonant-vowel-consonant words representing all
      possible initial consonants were presented as auditory, visual, or audiovisual
      speech in a gating task. The distribution of information over time varied across
      and within features. Visual speech information was generally fully available
      early during the phoneme, whereas auditory information was still accumulated. An
      audiovisual benefit was therefore already found early during the phoneme. The
      nature of the audiovisual recognition benefit changed, however, as more of the
      phoneme was presented. More features benefited at short gates rather than at
      longer ones. Visual speech information plays, therefore, a more important role
      early during the phoneme rather than later. The results of the study showed the
      complex interplay of information across modalities and time, since this is
      essential in determining the time course of audiovisual spoken-word recognition.

PMID- 20045889
TI  - Relative priming of temporal local--global levels in auditory hierarchical
      stimuli.
AB  - Priming is a useful tool for ascertaining the circumstances under which previous
      experiences influence behavior. Previously, using hierarchical stimuli, we
      demonstrated (Justus & List, 2005) that selectively attending to one temporal
      scale of an auditory stimulus improved subsequent attention to a repeated (vs.
      changed) temporal scale; that is, we demonstrated intertrial auditory temporal
      level priming. Here, we have extended those results to address whether level
      priming relied on absolute or relative temporal information. Both relative and
      absolute temporal information are important in auditory perception: Speech and
      music can be recognized over various temporal scales but become uninterpretable
      to a listener when presented too quickly or slowly. We first confirmed that
      temporal level priming generalized over new temporal scales. Second, in the
      context of multiple temporal scales, we found that temporal level priming
      operates predominantly on the basis of relative, rather than absolute, temporal
      information. These findings are discussed in the context of expectancies and
      relational invariance in audition.

PMID- 20045891
TI  - Aging and tactile temporal order.
AB  - Although it is generally held that speed of processing declines with age, there
      have been few studies in which tactile temporal processing has been examined with
      older subjects. In the present study, temporal order judgments were obtained from
      a group of younger subjects (n = 28, mean age = 23.5 years) and a group of older
      subjects (n = 93, mean age = 69.8 years). The subjects judged the temporal order
      of two patterns presented to the same finger, four patterns presented to the same
      finger, and two patterns presented to different hands. Depending on the task, the
      average thresholds for the older subjects ranged from two to five times longer
      than the thresholds from the younger subjects. In absolute terms, the largest
      difference between the young and older subjects was seen in correctly identifying
      the order of four patterns, a difference of more than 500 msec. There was some
      support for the decline in temporal processing being due in part to a slowing in
      cognitive processing, and, depending on the task, in part to stimulus persistence
      and difficulty in pattern identification.

PMID- 20045892
TI  - Grab it! Biased attention in functional hand and tool space.
AB  - This study explored whether functional properties of the hand and tools influence
      the allocation of spatial attention. In four experiments that used a visual
      orienting paradigm with predictable lateral cues, hands or tools were placed near
      potential target locations. Results showed that targets appearing in the hand's
      grasping space (i.e., near the palm) and the rake's raking space (i.e., near the
      prongs) produced faster responses than did targets appearing to the back of the
      hand, to the back of the rake, or near the forearm. Validity effects were found
      regardless of condition in all experiments, but they did not interact with the
      target-in-grasping/raking-space bias. Thus, the topology of the facilitated space
      around the hand is, in part, defined by the hand's grasping function and can be
      flexibly extended by functional experience using a tool. These findings are
      consistent with the operation of bimodal neurons, and this embodied component is
      incorporated into a neurally based model of spatial attention.

PMID- 20045893
TI  - Modeling reaction time and accuracy of multiple-alternative decisions.
AB  - Several sequential-sampling models using racing diffusion processes for multiple
      alternative decisions were evaluated, using data from two perceptual
      discrimination experiments. The structures of the models differed on a number of
      dimensions, including whether there was lateral inhibition between accumulators,
      whether there was decay in evidence, whether evidence could be negative, and
      whether there was variability in starting points. Data were collected from a
      letter discrimination task in which stimulus difficulty and probability of the
      response alternatives were varied along with number of response alternatives.
      Model-fitting results ruled out a large number of model classes in favor of a
      smaller number of specific models, most of which showed a moderate to high degree
      of mimicking. The best-fitting models had zero to moderate values of decay, had
      no inhibition, and assumed that the addition of alternatives affected the
      subprocesses contributing to the nondecisional time, the degree of caution, or
      the quality of evidence extracted from stimuli.

PMID- 20045894
TI  - A current from the heart is necessary for learning.

PMID- 20045895
TI  - Respiratory plasticity in sleep apnoea: should it be harnessed or restrained?

PMID- 20045896
TI  - Extending the bandwidth of long-term plasticity at the cerebellar input stage.

PMID- 20045897
TI  - Immature brains don't need GABA to get 'hyper'-excited.

PMID- 20045898
TI  - Myosin - still a good reference for skeletal muscle fibre classification?

PMID- 20045899
TI  - Sea anemone 'sting' isolates IB4-negative sensory neurones.

PMID- 20045900
TI  - Why a soft touch can hurt.

PMID- 20045901
TI  - How much inhibition in an epileptiform burst?

PMID- 20045902
TI  - Heart rate during haemorrhage: time for reappraisal.

PMID- 20045903
TI  - Muscle-to-fat interaction: a two-way street?

PMID- 20045904
TI  - Luttgau & Niedergerke; the classic study of calcium-sodium antagonism half a
      century on.

PMID- 20045905
TI  - To drink or not to drink: the effect of fluid replacement on post-exercise
      cardiovascular haemodynamics.

PMID- 20045906
TI  - Neurophysiology of inhibitory and excitatory amino acid receptors.

PMID- 20045907
TI  - The role of Loop F in the activation of the GABA receptor.
AB  - Functional studies of the ligand gated ion channel family (nicotinic
      acetylcholine, serotonin Type 3, glycine and GABA receptors) along with the
      crystal structure of the acetylcholine binding protein (AChBP) and molecular
      dynamics simulations of the nAChR structure have resulted in a structural model
      in which the agonist-binding pocket comprises six loops (A-F) contributed by
      adjacent subunits. It is presumed that the binding of agonist results in a local
      structural rearrangement that is then transduced to the gate, causing the pore to
      open. Efforts are underway to better define the specific roles of the six binding
      loops. Several studies have suggested Loop F may play a direct role in linking
      the structural rearrangement within the binding pocket to the gate, although
      other investigations have indicated Loop F may be crucial for locking the agonist
      molecule into the binding site. This review will focus on the controversy
      surrounding the role of Loop F during GABA receptor activation.

PMID- 20045908
TI  - Generation and identification of pluripotent stem cells from human embryonic
      fibroblast cells by 4 defined factors.
AB  - OBJECTIVE: To generate and identify the induced pluripotent stem cells (iPSCs)
      from human embryonic fibroblast cells (hEFs) by introducing 4 defined factors.
      METHODS: We introduced 4 factors (Oct4, Sox2, Nanog,and Lin28) into hEFs by
      lentivirus infection. The iPSCs generated from this method were analyzed in many
      aspects, including surface antigens, gene expression, and telomerase activity,
      differentiation ability in vivo and in vitro and the patterns of short tandem
      repeat (STR). RESULTS: The human iPSCs generated from this study were positive
      for alkaline phosphatase (AKP) staining, expressed hESCs-specific surface
      antigens, and exhibited high telomerase activity. They also possessed the ability
      to differentiate into 3-germ layers both in vivo and in vitro. STR analysis
      indicated that the human iPSCs were derived from the donor material. CONCLUSION:
      The iPSCs lines can be obtained from human embryonic fibroblast by introducing 4
      factors. Such human iPSCs should be useful in the study of epigenetic
      reprogramming and pluripotency maintenance.

PMID- 20045909
TI  - TGF-beta1-800G>A polymorphism and cerebral infarction in Chinese Han population.
AB  - OBJECTIVE: To investigate the association between transforming growth factor
      beta1(TGF-beta1)-800G>A polymorphism and cerebral infarction (CI). METHODS: The
      genotypes of 247 patients with atherosclerotic cerebral infarction and 167 sex-
      and age-matched healthy controls were detected by PCR-RFLP, and the frequency
      distribution of alleles calculated. RESULTS: TGF-beta1-800G>A polymorphism was
      found in Han population in Hunan Province, China. The distribution of -800G>A
      genotypes was consistent with Hardy-Weinberg balance in the CI and healthy
      control group. There was no significant difference between genotypes and allele
      frequency of TGF-beta1-800G>A in the CI and control group (P>0.05). Logistic
      regression analysis suggested that no genotypes could increase or reduce the risk
      of CI onset (P>0.05). CONCLUSION: TGF-beta1-800G>A polymorphism is not associated
      with CI in Han population in Hunan Province.

PMID- 20045910
TI  - [Marburg I polymorphism of Factor VII-activating protease and cerebral
      infarction].
AB  - OBJECTIVE: To determine the relation between Marburg I polymorphism of Factor VII
      activating protease (FSAP) and cerebral infarction,and to analyze whether it is
      one of the risk factors of cerebral infarction. METHODS: Single strand
      conformation polymorphism-polymerase chain reaction (SSCP-PCR) was applied for
      the polymorphism analysis of FSAP in 159 patients with cerebral infarction and
      179 non-cerebral infarction subjects. RESULTS: The phenotypes of FSAP in both the
      patients and the control subjects were wild type GG; no mutant of Marburg I was
      found. But a new gene mutation was tested, which had not been reported, requiring
      further investigation. CONCLUSION: Marburg I polymorphism of FSAP may not be
      associated with cerebral infarction.

PMID- 20045911
TI  - [Numerical simulation and heat transfer in sand therapy in Uyghur medicine].
AB  - OBJECTIVE: To investigate the mechanism of heat transfer process in sand therapy
      in Uyghur medicine. METHODS: A mathematical model was developed to describe the
      heat transfer process between human body and the sand during sand therapy.
      Temperature field was numerically simulated and analyzed based on this model.
      RESULTS: Temperature field in both human tissues and sand was calculated. The
      surface temperature of the sand and skin surface changed significantly at the
      beginning of the sand therapy, while sand temperature (5 cm deep) almost kept
      constant. The skin temperature dramatically increased at the beginning of the
      sand therapy and then slightly dropped. When sand was deeper than 10 cm, the
      thickness of sand would not influence the temperature field in human tissues
      during sand therapy. High initial temperature of sand might cause harmful skin
      burn. Threshold skin burn occurred if initial temperature of sand was higher than
      64.6 degree C and if the therapy lasted more than 30 minutes. CONCLUSION:
      Temperature fieled in human tissues varies significantly with the initial
      temperature of sand, thickness of sand, and duration of therapy.

PMID- 20045912
TI  - [Comparative proteome analysis of laser capture microdissection for purified
      primary tumor and lymph node metastatic tumor in human lung squamous carcinoma].
AB  - OBJECTIVE: To search for lymph node metastasis-associated proteins in human lung
      squamous carcinoma (hLSC). METHODS: Laser capture microdissection (LCM) was used
      to purify the target cells from lung primary tumor and matched lymph node
      metastatic tumor in hLSC. Two-dimensional gel electrophoresis (2-DE) was
      performed to separate the total proteins of microdissected tumor cells from lung
      primary tumor and matched lymph node metastatic tumor. PDQuest software was
      applied to analyze 2-DE images. Differential protein spots between the two types
      of tissues were identified by matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry (MALDI-TOF-MS). The expression of Rho-GDIalpha, one of
      the differential proteins, in the microdissected lung primary tumor cells (LPTC)
      and matched lymph node metastatic tumor cells (LNMTC) was detected by Western
      blot. RESULTS: In the present study, 2-DE patterns of microdissected LPTC and
      LNMTC were established, and 22 differential proteins in the above two tissues
      were identified, of which 14 were down-regulated in LNMTC and 8 were up-regulated
      in LNMTC. CONCLUSION: The 22 differential proteins may play some roles in the
      process of lymph node metastasis in hLSC, and the data provide new clues for
      metastasis-associated biomarker screen and mechanism of hLSC.

PMID- 20045913
TI  - [Transcription factors in spinal dorsal root ganglion in rats recurrently
      infected with respiratory syncytial virus].
AB  - OBJECTIVE: To elucidate intracellular transcription factor activation of C(7)
      approximately T(5) dorsal root ganglia in rats recurrently infected with
      respiratory syncytial virus (RSV). METHODS: Eighty 1 approximately 2 weeks old
      Sprague-Dawley rats were randomly divided into 2 groups: a control group and a
      RSV-infection group. The rats in the RSV-infection group were infected with 5 x
      10(5) U/mL RSV once a week and the rats in the control group were treated with
      culture medium without RSV. Airway response was measured after 8 weeks. Lung
      tissue was submitted for HE staining and in situ hybridization. The C(7)
      approximately T(5) dorsal root ganglia were obtained for the preliminary
      screening of the intracellular transcription factors by TranSignal protein/DNA
      combo array. Nuclear protein of C(7) approximately T(5) dorsal root ganglia were
      extracted and submitted to Western blot. RESULTS: Airway response in the RSV
      infection group was higher than that in the control group (P<0.05). HE staining
      showed inflammatory cell infiltration, and in situ hybridization demonstrated
      positive RSV RNA in the RSV-infection rat lung which was not present in the
      control group, thus validating the efficacy of our model. TranSignal protein/DNA
      combo array screening showed that 55 transcription factors increased by at least
      2 folds in the C(7) approximately T(5) DRG cells of the RSV-infection group. The
      transcription factors Smad and interferon regulatory factor (1 or 2) were the 2
      most upregulated transcription factors identified by combo array screening (59
      and 43 fold increase compared with the control, respectively). Western blot
      confirmed Smad(1/2/3) and IRF-1 upregulate while IRF-2 remained unchanged.
      CONCLUSION: Respiratory syncytial virus infection results in airway
      hyperresponsiveness and transcription factor activation in C(7) approximately
      T(5) spinal adorsal root ganglia in rats, which may contribute to airway nerve
      network dysfunction and airway hyperresponsiveness.

PMID- 20045914
TI  - [MucA mutation and its alginate-production in clinically isolated Pseudomonas
      aeruginosa].
AB  - OBJECTIVE: To determine the characterization of mucA gene mutation in clinically
      isolated Pseudomonas aeruginosa (P.aeruginosa), and the relation between mucA
      mutation and the mucoid phenotype. METHODS: A total of 58 strains of P.
      aeruginosa were collected. Of them, 8 were nonmucoid phenotype and 50 were mucoid
      phenotype. We detected mucA mutations with PCR-SSCP and sequencing analysis.
      Alginate was examined by colorimetry. RESULTS: All strains had mucA mutations
      (100%), 16 of the 50 (32%) isolates contained mucA mutations that could alter the
      encoding sequence of amino acids, and the rate in nonmucoid isolates was 0.
      Fourteen mutation sites were found, 5 of which could alter the encoding sequence
      of amino acids, and the others were silent mutations. The alginate concentration
      of mucoid P.aeruginosa was higher than the nonmucoid P. aeruginos (P<0.01). The
      alginate concentration of the isolates which contained mucA mutations that could
      alter the encoding sequence of amino acid was higher than the strains only with
      silent mutations (P<0.01). CONCLUSION: MucA mutation correlates with the alginate
      production and phenotype of bacterial colonies.

PMID- 20045915
TI  - [Cholecystokinin stimulates peptide chain elongation in mouse pancreatic acini
      and its molecular mechanism].
AB  - OBJECTIVE: To investigate cholecystokinin (CCK), carbachol, and vasoactive
      intestinal peptide (VIP) stimulating peptide chain elongation in mouse pancreatic
      acini in vitro and its molecular mechanism. METHODS: (3)H-lecucine incorporation
      assay was used to measure the basal and secretagogues-stimulated pancreatic acini
      elongation rates. Western blot was applied to analyse the effect of
      phosphorylation of the elongation factor 2 (eEF2) and the eEF2 kinase. MEK
      inhibitor (PD98059), SAPK/p38 inhibitor (SB202190), and mTOR inhibitor
      (rapamycin) were used to respectively block MEK, SAPK/p38, and mTOR intracellular
      pathways or the phosphatase inhibitor (calyculin A) pretreatment before CCK
      treatment. RESULTS: All secretagogues except VIP increased the peptide chain
      elongation in mouse pancreatic acini in vitro. All secretagogues except VIP
      inhibited the phosphorylation level of eEF2 on Thr-56 and increased the
      phosphorylation level of eEF2K on Ser-366, which might correlate with their
      activation status. MEK inhibitor PD98059 partially reversed the dephosphorylation
      of eEF2 induced by CCK, as did treatment p38 MAPK inhibitor SB202190, mTOR
      inhibitor rapamycin, and the phosphatase inhibitor calyculin A. CONCLUSION: CCK
      increases peptide chain elongation via inducement of dephosphorylation of eEF2
      and eEF2 kinase phosphorylation in pancreatic acini in vitro. CCK-induced
      dephosphorylation of eEF2 in pancreatic acinar cells involves MEK, SAPK/p38, and
      mTOR, the three intracellular pathways.

PMID- 20045916
TI  - [Serum and urine VEGF concentration of different pathological types in children
      with Henoch Schonlein purpura nephritis].
AB  - OBJECTIVE: To explore the relationship between vascular endothelial growth factor
      (VEGF) concentration in urine and renal vascular damage in children with Henoch
      Schonlein purpura nephritis (HSPN). METHODS: The kidney pathological lesion of 78
      biopsy-proven HSPN children was assessed with renal vascular damage, glomerular
      pathological damage, and tubulointerstitial pathological damage semi-quantitative
      points. The children were divided into 3 groups (light, medium, and heavy group)
      according to the renal vascular, glomerular, tubulointerstitial, glomerular and
      tubulointerstitial total pathological points. Blood and urine vascular
      endothelial growth factor concentration was detected by enzyme linked
      immunosorbent assay; the localized renal VEGF expression and microvessel density
      were detected by immunohistochemistry assay in the kidneys. RESULTS: The semi
      quantitative points of glomerular, tubulointerstitial, renal vascular, and
      glomerular and tubulointerstitial total points in different groups had
      significant difference (all P<0.01); the minor renal vascular damage, the higher
      light microvessel density, blood and kidney concentration of VEGF, and the VEGF
      excretion in the urine were also lower in different groups, and there were
      significant differences (all P<0.01). Glomerular points were positively related
      with tubular points, vascular points, kidney total score (r=0.596, 0.612, and
      0.728; P<0.05, 0.05, and 0.01 respectively). Microvessel density was highly
      positively related with blood VEGF and renal VEGF, and negatively related with
      urine VEGF (r=0.601, 0.696, and -0.639, all P<0.01). CONCLUSION: The urinary
      excretion of VEGF leads to the decrease of local kidney VEGF concentration
      resulting in the renal vascular injury, which may be the important reason for
      renal vascular damage and pathology chronic progress in HSPN children.

PMID- 20045917
TI  - [Effect of Qufengtongluo recipe on expression of nephrin mRNA in adriamycin
      induced nephropathy in rats].
AB  - OBJECTIVE: To investigate the expression of nephrin mRNA in adriamycin-induced
      nephropathy (AN) in rats, and to explore the effect of Qufengtongluo recipe on
      proteinuria in AN rats and on the expression of nephrin mRNA. METHODS: Adriamycin
      nephropathy was induced by a single tail intravenous injection of adriamycin. We
      randomly divided 140 rats into a normal control group (n=32) and a nephropathy
      model group (n=108). Three weeks later, 90 AN rats were randomly divided into 5
      groups: a model group, a qufeng group, a qufeng and prednisone group, a
      prednisone group, and a benazepri group (18 rats in each group). They were
      treated respectively, and renal tissue samples were collected at week 0, 3, 5,
      and 7, respectively. The distribution and expression of nephrin mRNA were
      examined by indirect immunofluorescence and semi-quantity RT-PCR. RESULTS: In the
      AN rats, the diffuse fusion and effacement of foot processes were observed at
      week 3. The fluorescence intensity of nephrin and the expression of nephrin mRNA
      significantly increased in the qufeng group and the prednisone group compared
      with the model group at the week 7 (P<0.01). CONCLUSION: Abnormal expression of
      nephrin is the important molecular mechanism that leads to the occurrence and
      development of proteinuria in AN rats. Qufengtongluo recipe has effect on
      nephrotic syndrome through altering the expression and distribution of nephrin in
      glomerulus.

PMID- 20045918
TI  - [Effect of PTD-deltaPRD Foxp3 fusion protein on the mixed lymphocyte reaction in
      mice].
AB  - OBJECTIVE: To express protein transduction domain (PTD)-deletion proline domain
      (deltaPRD) Foxp3 fusion protein, and to analyze its influence on mixed lymphocyte
      reaction in mice. METHODS: We cloned mouse deltaPRD of Foxp3 gene by PCR, and
      inserted it into pET28a-PTD, pET28a-PTD-eGFP vector, then expressed fusion
      proteins in E.coli Rosetta (DE3). The fusion proteins were purified and refolded
      by Profinity IMAC Ni(2+)-Charged Resin. The expression of fusion proteins was
      identified by Western blot. Flow cytometry assay was used to detect the effect of
      PTD-deltaPRD fusion protein to transduce into mouse EL-4 cells. The ability of
      fusion protein to inhibit the proliferation of EL-4 cells was analyzed by two-way
      mixed lymphocyte reaction. RESULTS: The PTD-deltaPRD fusion proteins were
      expressed and purified efficiently. Western blot and flow cytometry indicated
      that PTD-deltaPRD fusion protein was transduced into EL-4 efficiently. Mixed
      lympocyte reaction assay showed that PTD-deltaPRD fusion protein had the
      bioactivity to inhibit the proliferation of EL-4 cells. CONCLUSION: The PTD
      deltaPRD fusion protein was expressed in E.coli system and could be transduced
      into cells effectively, suggesting that PTD-deltaPRD fusion protein may be an
      inhibitor in lymphocytes from mouse spleen.

PMID- 20045919
TI  - [Construction of adenoviral vector encoding Calponin-1 siRNA and its effect on
      human myometrium cells in vitro].
AB  - OBJECTIVE: To investigate the effect of Calponin-1 suppression on human
      myometrium cells through adenovirus mediated siRNA. METHODS: Human uterine smooth
      muscle tissues were digested with enzymes, cultured and confirmed with
      immunocytochemistry. Adenovirus siRNA-Calponin-1 plasmid was transfected into
      primary cultured uterine smooth muscle cells in vitro. The expressions of
      Calponin-1 mRNA and protein were analyzed by RT-PCR and Western blot,
      respectively. RESULTS: The pAdEasy-pShuttle-U6-Calponin-1 siRNA plasmid was
      successfully constructed, and Calponin-1 siRNA mediated by recombinant adenovirus
      resulted in markedly reduced expression of Calponin-1 mRNA and protein in human
      myometrium cells. The gray values of Calponin-1 mRNA in the uterine smooth muscle
      cells in the experimental, blank control, and empty vector groups were 316.3+/
      39.2, 1048.5+/-126.4 and 1027.2+/-127.5, respectively. The gray values of
      Calponin-1 protein were 323.3+/-43.2, 1021.5+/-143.4, and 1019.2+/-144.5,
      respectively. The difference between the experimental group and the blank control
      group as well as the empty vector group was significant (P< 0.05). There was no
      significant difference between the empty vector group and the blank control group
      (P>0.05). CONCLUSION: The pAdEasy-pShuttle-U6-Calponin-1 siRNA plasmid can
      inhibit the expression of Calponin-1 in human myometrium cells in vitro, which
      may be a useful approach to determine the role of Calponin-1 in delivery.

PMID- 20045920
TI  - [Expression of peroxisome proliferator-activated receptor gamma in hippocampus
      neurons in rats after oxygen deprivation/oxygen supply in vitro].
AB  - OBJECTIVE: To observe the expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma) in hippocampus neurons in rats after different time of
      neuron oxygen deprivation/oxygen supply, and to investigate the role of PPARgamma
      in neuron ischemia reperfusion injury. METHODS: One day old newborn SD rats were
      chosen. Primary cultured hippocampus neurons were used to establish neuron
      ischemic reperfusion model in vitro by oxygen and glucose depriving 15 minutes
      and supplying again, and then the neuron structure was observed by transmission
      electron microscope of JEM-200EX. The expression of PPARgamma mRNA and protein
      were detected by RT-PCR and Western blot, respectively. RESULTS: Neuron structure
      was damaged after neuron oxygen deprivation/oxygen supply. There was no
      significant difference between 0 h oxygen supply group and the control group. The
      expression of PPARgamma was decreased both at mRNA and protein level after 6 h of
      oxygen supply. The difference between 6 h oxygen supply group and the control
      group was significant (P<0.01), which decreased with the length of reperfusion
      and the lowest was at 48 h after the reperfusion. The difference among the
      different reperfusion groups and the control group was significant (P<0.01).
      CONCLUSION: PPARgamma may participate in the pathological damage course of neuron
      ischemical reperfusion injury, and may become a new intervention target of
      treatment for ischemic cerebrovascular disease.

PMID- 20045921
TI  - [Expression and meaning of pro-angiogenic factors in retinopathy of diabetic
      rats].
AB  - OBJECTIVE: To detect the expression of vascular endotheilal growth factor (VEGF),
      stromal cell-derived factor-1alpha (SDF-1alpha), and its receptor CXCR-4 in the
      retinopathy of diabetic rats, and to explore the relationship between those
      factors and diabetic-retinopathy (DR). METHODS: Diabetes was induced in 40 rats
      with a single intraperitional injection of streptozotocin(STZ). Experimental rats
      were randomly divided into M1 (diabetic for 1 month), M3 (diabetic for 3 months),
      and M5 (diabetic for 5 months) groups, and another 10 rats served as a normal
      control group (NC). Retinal vascular status was observed by transmission electron
      microscope. After retinal stretched preparation, VEGF, SDF-1alpha and CXCR-4
      immunohistochemistry were done. Retinal VEGF, SDF-1alpha, and CXCR-4 mRNA were
      detected by semi-quantitative RT-PCR. Protein expression was measured by Western
      blot. RESULTS: Under transmission electron microscope, change in vascular status
      was found in M1 to M5 groups, but not in the NC group. The changes became
      increasingly serious with the prolongation of the disease. By
      immunohistochemistry, we found the expression of VEGF, SDF-1alpha, and CXCR-4 on
      the retina increased gradually. It increased after injecting STZ for 1 month and
      increased significantly after 5 months. VEGF, SDF-1alpha, and CXCR-4 mRNA
      expression increased obviously after injecting STZ for 1 month and increased
      significantly after 5 months. Western blot showed that protein of VEGF, SDF
      1alpha, and CXCR-4 had no change after injecting STZ for 1 month. It began to
      increase in the M3 group and increased most in the M5 group. CONCLUSION: The
      expression of VEGF, SDF-1alpha, and CXCR-4 on the retina in retinopathy of
      diabetic rats increases gradually with the prolongation of the disease. It is an
      important factor for diabetic retinopathy.

PMID- 20045922
TI  - [Anti-Helicobacter pylori treatment in patients with idiopathic thrombocytopenic
      purpura].
AB  - OBJECTIVE: To observe the effect of anti-Helicobacter pylori (H.pylori) treatment
      on patients with idiopathic thrombocytopenic purpura (ITP) and its effect on
      blood platelet. METHODS: From April 2006 to April 2008, a total of 31 patients
      diagnosed as having ITP and H. pylori infection were collected. These patients
      were given standard antibiotic therapy for H. pylori eradication (omeprazole 20
      mg, clarithromycin 0.5 g, and amoxicillin 1.0 g, twice per day for 1 week). The
      effect of anti-H. pylori treatment was analyzed, and the blood platelets were
      counted before the treatment and on day 7, 14, and 28 after the treatment.
      RESULTS: Of the 31 ITP patients with H. pylori infection, 21 were cured and 10
      were not effective, with the effective rate 67.74%. Blood platelet increased in
      the cured group but did not change in the no-effect group. CONCLUSION: Anti-H.
      pylori treatment could increase the blood platelet, and H. pylori infection may
      be related to the reduction of blood platelet in ITP patients.

PMID- 20045923
TI  - [Preparation and preliminary evaluation of KGDS-targeted ultrasound contrast
      agent].
AB  - OBJECTIVE: To prepare a thrombus-targeted ultrasonic contrast agent and to
      investigate its targeted ability to fresh blood clots. METHODS: We first
      synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted
      microbubbles using "ultrasound & high speed shearing method". Fluorescence
      labeling thrombus-specific peptides and KGDS, directed at the activated
      glycoprotein(GP)IIb/IIIa receptor of platelets were attached to the surface of
      lipid microbubbles. The concentration and size of TUCA were measured by Malvern
      Zeta Sizer Nano-ZS590 and Coulter counter. Immunofluorescence was applied to
      confirm the conjugation. The conjunct ratio was assessed by flow cytometer (FCM).
      RESULTS: The KGDS-TUCA was straw yellow turbid liquor, and the concentration was
      1.5 x 10(9)/mL, and the average size was 1.5 microm. The targeted microbubbles
      conjugated with the thrombus-specific peptides showed bright green rings by
      fluorescence microscope. FCM demonstrated that the wavelength of shell of KGDS
      TUCA changed greatly, and the conjunct ratio was 90.04%. In vitro study showed
      KGDS-TUCA remained stable for 48 h at 4 degree C and target-attached to blood
      clots and showed good stability. CONCLUSION: The ultrasound & high speed shearing
      method to prepare TUCA is easy and in favor of purification. KGDS-TUCA has high
      specific biological activity. The conjunct ratio and stability of KGDS-TUCA are
      excellent.

PMID- 20045924
TI  - [Noonan syndrome: a case report and literature review].

PMID- 20045925
TI  - [Colorectal carcinoma and DNA methylation].
AB  - Epigenetic regulation involved in eukaryotic gene expression plays an important
      role in the progression of colorectal cancer. Colorectal cancer epigenetics is
      evolved in DNA methylation which is associated with the activation of oncogene
      and inactivation of tumor suppressor gene. The potential reversibility of DNA
      methylation offers exciting opportunities for therapy and diagnosis of colorectal
      carcinoma.

PMID- 20045927
TI  - Increase in in utero exposure to a migrant, 4,4'-butylidenebis(6-t-butyl-m
      cresol), from nitrile-butadiene rubber gloves on brain aromatase activity in male
      rats.
AB  - 4,4'-Butylidenebis(6-t-butyl-m-cresol) (BBBC) can be eluted from disposable
      gloves made of nitrile-butadiene rubber and possibly also detected in food. It
      has been reported that BBBC is an androgen and estrogen antagonist in vitro.
      Previously, BBBC (1.0 mg/kg body weight (bw)/d) was subcutaneously administered
      to pregnant rats from gestation days 11 through 18, and the effects on male
      offspring (postnatal day 102) were examined. Altered levels and turnover of the
      monoamines dopamine, serotonin, and noradrenalin as well as their metabolites
      were detected. This report measured the level of serum testosterone following
      prenatal exposure to BBBC (0.1, 1.0, 10 mg/kg bw/d) in male rats, and measured
      aromatase activity of the hypothalamus-preoptic area with a close connection to
      the sexual differentiation and sexual behavior of BBBC-treated rat brains. The
      serum testosterone level rose depending on exposure, and aromatase activity of
      the basomedial nucleus of amygdale region was increased in the BBBC-treated group
      compared with the control. These results suggested that prenatal exposure to BBBC
      affects the central nervous system of male rat offspring, and BBBC may be an
      endocrine disrupting-chemical during the fetal period, and might influence the
      functional development of the brain.

PMID- 20045926
TI  - Deoxypodophyllotoxin inhibits the expression of intercellular adhesion molecule-1
      induced by tumor necrosis factor-alpha in murine lung epithelial cells.
AB  - Intercellular adhesion molecule-1 (ICAM-1) is associated with processes of
      inflammation. We investigated the effects of deoxypodophyllotoxin (DPT) on tumor
      necrosis factor-alpha (TNF-alpha) induced ICAM-1 expression in the mouse lung
      epithelial cell line, LA4. DPT (5 to 20 nM) inhibited TNF-alpha-induced ICAM-1
      expression through nuclear factor-kappa B (NF-kappaB) in a dose-dependent manner
      and repressed ICAM-1 promoter activity. NF-kappaB reporter gene activity and DNA
      binding activity were also strongly inhibited. In addition, DPT inhibited
      degradation by the TNF-alpha induced inhibitory kappaB-alpha (IkappaB-alpha) in a
      concentration-dependent manner. Taken together with our previous results suggest
      DPT might provide a basis for novel anti-inflammatory drug development.

PMID- 20045928
TI  - Involvement of ceramide in ischemic tolerance induced by preconditioning with
      sublethal oxygen-glucose deprivation in primary cultured cortical neurons of
      rats.
AB  - The complex molecular cascades of ischemic tolerance in brain cells remain
      unclear. Recently, sphingolipid-related metabolite ceramide has been implicated
      as a second messenger in many biological functions, including neuronal survival
      and death. The present study, therefore, examined the roles of ceramide (Cer) in
      ischemic tolerance induced by preconditioning with sublethal oxygen-glucose
      deprivation (OGD) using primary cultured cortical neurons of rats.
      Preconditioning of the neurons with sublethal 1-h OGD produced robust
      neuroprotection against cell death induced by lethal 3-h OGD imposed 12 h after
      preconditioning when measured by the MTT assay. Analysis of sphingolipids using
      LC-MS/MS showed that the ischemic preconditioning resulted in significant
      increases in the levels of C(16 : 0) Cer, C(18 : 0) Cer, C(20 : 0) Cer, C(24 : 0)
      Cer, C(24 : 1) Cer and the total ceramide contents compared with the sham-washed
      control group. However, sphingomyelin contents were not significantly changed by
      the ischemic preconditioning, suggesting that ceramides were increased through
      the de novo synthetic pathway. In the case of severe OGD paradigm, levels of
      ceramide and sphingomyelin in the lethal OGD group were not significantly
      different from those of the control group or the lethal OGD group with
      preconditioning at any time points studied. Treatment with an inhibitor of de
      novo ceramide synthesis, fumonisin B(1), during the ischemic preconditioning
      period completely blocked preconditioning-induced ischemic tolerance. Moreover,
      application of a non-cytotoxic concentration of exogenous cell-permeable ceramide
      produced neuroprotection against lethal OGD. The results suggest that ceramides
      increased by sublethal OGD preconditioning play an important role in induction of
      ischemic tolerance.

PMID- 20045929
TI  - Expression of the Parkinson's disease-related protein DJ-1 during neural stem
      cell proliferation.
AB  - Neural stem cells (NSCs) arise through neurogenesis, and comprise all newly
      formed neurons in the central and peripheral nervous systems. DJ-1 is associated
      with autosomal recessive familial Parkinson's disease (PD). The relationship
      between DJ-1 and NSC proliferation may shed light on the underlying pathogenesis
      of, and potential treatments for, PD. To investigate the relationship between DJ
      1 and NSCs, embryonic cortical NSCs were isolated and cultured from E14 fetal
      rats. Immunocytochemistry, flow cytometry, and immunohistochemistry were applied
      to evaluate DJ-1 expression in proliferating NSCs. We found that DJ-1 was co
      expressed with nestin, a marker of progenitors, during NSC proliferation from
      days 1-7. The present results suggest that DJ-1 is co-expressed with nestin in
      NSCs during proliferation.

PMID- 20045930
TI  - Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome
      inhibition in primary cultured neurons and astrocytes.
AB  - We reported previously that N-linked glycoproteins were accumulated in the
      cytosol of the normal aging rat brain, and that one protein had been identified
      as cathepsin D (Mech. Ageing Dev., 127, 771-778 (2006)). In this study, to
      elucidate the mechanism of cathepsin D accumulation in the cytosol, we examined
      the effects of oxidative stress and proteasome inhibition on the apoptosis and
      subcellular localization of cathepsin D in primary cultured neurons and
      astrocytes. Using 4'-6-diamidino-2-phenylindole (DAPI)- or Hoechst 33342-staining
      and annexin V detection, we found that oxidative stress caused by tert-butyl
      hydroperoxide and proteasome inhibition by lactacystin induced apoptosis in
      neurons and astrocytes. Furthermore, after cell fractionation, it was
      demonstrated that cathepsin D was translocated from lysosomes to cytosol under
      apoptosis-inducing conditions in both cells. These results suggested that
      oxidative stress and the suppression of proteasome activity triggered the
      translocation of cathepsin D from lysosomes to cytosol. The possible mechanism of
      age-related accumulation of cathepsin D in the cytosol of the normal rat brain
      will be discussed.

PMID- 20045931
TI  - Ferulic acid protects human umbilical vein endothelial cells from radiation
      induced oxidative stress by phosphatidylinositol 3-kinase and extracellular
      signal-regulated kinase pathways.
AB  - Ferulic acid (FA) has been demonstrated to have a remarkable antioxidant
      activity, the mechanism of FA of protecting human umbilical vein endothelial
      cells (HUVECs) from radiation induced oxidative stress was investigated in the
      present study. The oxidative protection of FA was assessed by cellular
      glutathione (GSH) content, nicotinamide adenine dinucleotide phosphate (NADPH)
      levels, and reactive oxygen species (ROS) analysis. Nuclear factor erythroid 2
      related factor 2 (Nrf2) nuclear translocation was detected using Western
      blotting. The upstream signaling pathway involved in FA mediated Nrf2 activation
      was determined by signaling inhibitors. FA significantly increased the
      transcription of antioxidant related genes such as GCLC (glutamate-cysteine
      ligase catalytic subunit), GCLM (glutamate-cysteine ligase regulatory subunit),
      NQO1 (NADPH quinone oxidoreductase-1) and heme oxygenase-1 (HO-1) mRNA in
      radiated cells, and these changes involved in a significant increase of the
      intracellular GSH content and the expression of NAPDH. FA evidently promoted Nrf2
      translocation into nuclei and increased the intracellular GSH and NADPH levels in
      radiated cells. Phosphatidylinositol 3-kinase (PI3K) and extracellular signal
      regulated kinase (ERK) pathways were associated with FA-induced Nrf2 activation.
      The results suggested that FA-induced Nrf2 activation play key role in
      cytoprotective effect of FA against oxidative stress via PI3K and ERK signaling
      pathways.

PMID- 20045932
TI  - Proline-rich domain plays a crucial role in extracellular stimuli-responsive
      translocation of a Cdc42 guanine nucleotide exchange factor, FGD1.
AB  - We previously demonstrated that FGD1, the Cdc42 guanine nucleotide exchange
      factor (GEF) responsible for faciogenital dysplasia, and its homologue FGD3 are
      targeted by the ubiquitin ligase SCF(FWD1) upon phosphorylation of two serine
      residues in their DSGIDS motif and subsequently degraded by the proteasome. FGD1
      and FGD3 share highly homologous Dbl homology (DH) and adjacent pleckstrin
      homology (PH) domains, both of which are responsible for GEF activity. However,
      their function and regulation are remarkably different. Here we demonstrate
      extracellular signal-responsive translocation of FGD1, but not FGD3. During the
      wound-healing process, translocation of FGD1 to the leading edge membrane occurs
      in cells facing to the wound. Furthermore, epidermal growth factor (EGF)
      stimulates the membrane translocation of FGD1, but not FGD3. As the most striking
      difference, FGD3 lacks the N-terminal proline-rich domain that is conserved in
      FGD1, indicating that proline-rich domain may play a crucial role in signal
      responsive translocation of FGD1. Indeed, there is a faciogenital dysplasia
      patient who has a missense mutation in proline-rich domain of FGD1, by which the
      serine residue at position 205 is substituted with isoleucine. When expressed in
      cells, the mutant FGD1 with S(205)/I substitution fails to translocate to the
      membrane in response to the mitogenic stimuli. Thus we present a novel mechanism
      by which the activity of FGD1, a GEF for Cdc42, is temporally and spatially
      regulated in cells.

PMID- 20045933
TI  - Matrine induces cell anergy in human Jurkat T cells through modulation of mitogen
      activated protein kinases and nuclear factor of activated T-cells signaling with
      concomitant up-regulation of anergy-associated genes expression.
AB  - Induction of immunotolerance has become a new strategy for treating autoimmune
      conditions in recent decades. However, so far there is no ideal therapeutics
      available for clinical use. Medicinal herbs are a promising potential source of
      immunotolerance inducers. In the current study, we sought first to optimize
      conditions for a validated cellular model of human Jurkat cells; and then used
      this model to screen bioactive compounds derived from medicinal plants for
      inducing T cell anergy in comparison with the effect of well-known T cell anergy
      inducer, ionomycin. The results showed that passage of the cells, and
      concentration and stimulation time of ionomycin on the cells could influence the
      ability of T cell anergy induction. Matrine, a small molecule derived from the
      root of Sophora flavescens AIT., was demonstrated to be effective in inducing T
      cell anergy in human Jurkat cells. The cells exposed to matrine showed markedly
      decreased mRNA expression of interleukin-2, an indicator of T cell anergy, when
      the cells were stimulated by antigens, anti-OKT3 plus anti-CD28. Mechanistic
      study showed that ionomycin and matrine could up-regulate the anergy-associated
      gene expressions of CD98 and Jumonji and activate nuclear factor of activated T
      cells (NFAT) nuclear translocation in absence of cooperation of AP-1 in Jurkat
      cells. Pre-incubation with matrine or ionomycin could also shorten extracellular
      signal-regulated kinase (ERK) and suppress c-Jun NH(2)-terminal kinase (JNK)
      expression on the anergic Jurkat cells when the cells were stimulated with anti
      OKT-3 plus anti-CD28 antibodies. Thus, matrine is a strong candidate for further
      investigation as a T cell immunotolerance inducer.

PMID- 20045934
TI  - Calcium channel inhibitor, verapamil, inhibits the voltage-dependent K+ channels
      in rabbit coronary smooth muscle cells.
AB  - We investigated the effect of the phenylalkylamine Ca(2+) channel inhibitor
      verapamil on voltage-dependent K(+) (Kv) channels in rabbit coronary arterial
      smooth muscle cells using a whole-cell patch clamp technique. Verapamil reduced
      the Kv current amplitude in a concentration-dependent manner. The apparent K(d)
      value for Kv channel inhibition was 0.82 microM. Although verapamil had no effect
      on the activation kinetics, it accelerated the decay rate of Kv channel
      inactivation. The rate constants of association and dissociation by verapamil
      were 2.20+/-0.02 microM(-1) s(-1), and 1.79+/-0.26 s(-1), respectively. The
      steady-state activation and inactivation curves were unaffected by verapamil. The
      application of train pulses increased the verapamil-induced Kv channel
      inhibition. Furthermore, verapamil increased the recovery time constant,
      suggesting that the inhibitory effect of this agent was use-dependent. The
      inhibitory effect of verapamil was not affected by intracellular and
      extracellular Ca(2+)-free conditions. Another Ca(2+) channel inhibitor,
      nifedipine (10 microM) did not affect the Kv current, and did not alter the
      inhibitory effect of verapamil. Based on these results, we concluded that
      verapamil inhibited Kv current in a state-, time-, and use-dependent manner,
      independent of Ca(2+) channel inhibition.

PMID- 20045935
TI  - Enhanced expression of BCL2/adenovirus EIB 19-kDa-interacting protein 3 mRNA, a
      candidate for intrinsic depression-related factor, and effects of imipramine in
      the frontal cortex of stressed mice.
AB  - We previously reported that long-term treatment with some antidepressants at low
      concentrations upregulates BCL2/adenovirus E1B 19-kDa-interacting protein 3
      (BNIP3) mRNA expression in NG108-15 cells without causing cell damage, suggesting
      that BNIP3 is a candidate of intrinsic depressive disorder-related factor(s). In
      this study, to clarify the physiologic functions of BNIP3, we investigated
      whether BNIP3 is actually related to the depressive condition in the brain using
      learned helplessness (LH) mice, an animal model of depression. Based on the score
      of escape failure, an index of depression degree, stressed animals were divided
      into groups with LH and without depressive-like symptoms (i.e., non-depressed
      phenotype, non-LH). The score of escape failure of the LH group was decreased
      after 14 d of treatment with imipramine in a dose-dependent manner. BNIP3 mRNA
      expression was enhanced in both the LH and non-LH groups. Imipramine treatment at
      5 and 20 mg/kg/d enhanced BNIP3 mRNA expression only in the LH group but not in
      non-LH group or non-stressed group. These results raise the possibility that
      BNIP3 acts as an antistress factor in the brain.

PMID- 20045936
TI  - R-(-)-alpha-methylhistamine, a histamine H3 receptor agonist, induces endothelium
      dependent vasodilation in rat mesenteric resistance arteries.
AB  - A novel histamine receptor subtype, histamine H(3) receptor, mediates inhibition
      of peripheral autonomic neurotransmission. The present study was designed to
      examine vascular effects of histamine H(3) receptor by using a selective
      histamine H(3) receptor agonist, R-(-)-alpha methylhistamine (alpha
      methylhistamine), in rat mesenteric resistance arteries. The isolated mesenteric
      vascular beds were perfused with Krebs solution and perfusion pressure was
      measured. Active tone was produced by perfusion of Krebs solution containing 7
      microM methoxamine. In preparations with intact endothelium, perfusion of alpha
      methylhistamine (1-100 microM) for 1 min produced a concentration-dependent
      vasodilation. The maximum vasodilation at the highest concentration was
      approximately 45%. This vasodilation was abolished by endothelium removal and
      attenuated by histamine H(3) receptor antagonists, thioperamide and clobenpropit,
      but not by chlorpheniramine (histamine H(1) receptor antagonist) and cimetidine
      (histamine H(2) receptor antagonist). N(omega)-nitro-L-arginine methyl ester (L
      NAME, nitric oxide (NO) synthase inhibitor), indomethacin (cyclooxygenase
      inhibitor) and tetraethylammonium (nonselective K(+)-channel blocker) and high
      KCl (30 mM) significantly inhibited alpha-methylhistamine-induced endothelium
      dependent vasodilation. These findings suggest that alpha-methylhistamine induces
      endothelium-dependent vasodilation mainly via endothelium histamine H(3)
      receptors. It is also suggested that activation of histamine H(3) receptors in
      the endothelium releases mainly NO and partially prostaglandin I(2) and
      endothelium-derived hyperpolarizing factors to induce endothelium-dependent
      vasodilation.

PMID- 20045937
TI  - Participation of prostaglandin E2 receptor in nasal congestion of Brown Norway
      rats.
AB  - The aim of the present study was to clarify the involvement of prostaglandin E(2)
      (PGE(2)) in nasal congestion in Brown Norway (BN) rats. For this purpose, we
      studied the effects of PGE(2) receptor (EP(1), EP(2), EP(3) and EP(4)) agonists
      on nasal congestion and sneezing induced by toluene 2,4-diisocyanate (TDI).
      Enhanced pause (Penh) was increased 1 h (early phase) and 4 h (late phase) after
      TDI challenge. Sulprostone (an EP(3) receptor agonist) inhibited the increase of
      Penh, an index of nasal congestion, in both early and late phase responses. On
      the other hand, PGE(1) alcohol (an EP(4) agonist) increased Penh in the early
      phase response. Moreover, sulprostone inhibited sneezing, an immediate response
      by TDI challenge. These results indicate that EP(3) receptor is responsible for
      the relief of nasal congestion in both early and late phase responses, and EP(4)
      receptor is correlated with the development of nasal congestion in the early
      phase response. In addition, EP(3) receptor also participates in sneezing in
      allergic rhinitis induced by TDI challenge in BN rats.

PMID- 20045938
TI  - The involvement of aldose reductase in alterations to neurotrophin receptors and
      neuronal cytoskeletal protein mRNA levels in the dorsal root ganglion of
      streptozotocin-induced diabetic rats.
AB  - Dorsal root ganglia (DRG) are recognized as one of the organs which are damaged
      in peripheral sensory diabetic neuropathy. In an experimental animal model, the
      alteration of the mRNA expression level of neurotrophins, their receptors and
      neuronal cytoskeletal protein have been reported. In this study, we examined
      whether these changes are improved by treatment with the aldose reductase
      inhibitor, zenarestat, in early-stage diabetic neuropathy of streptozotocin (STZ)
      induced diabetic rats. Two weeks after the induction of diabetes mellitus by STZ
      treatment, zenarestat or a vehicle were given orally for two weeks. After the
      zenarestat treatment, the mRNA expression levels of neurotrophin receptors and
      neuronal cytoskeletal proteins in dorsal root ganglia were determined with a real
      time polymerase chain reaction (PCR) method. Compared with the expression level
      of normal rats, a significant increase in Trk-C and Talpha1 alpha-tubulin and a
      decrease in neurofilament H mRNA expression level were observed in the DRG of STZ
      rats, while there were no significant changes in Trk-A, Trk-B, p75, neurofilament
      L, neurofilament M and betaIII tubulin mRNA expression. Zenarestat treatment
      significantly ameliorated the abnormal increase in Trk-C mRNA expression level.
      These data suggest that hyperactivation of the polyol pathway induces a deficit
      in neurotropism on peripheral sensory diabetic neuropathy.

PMID- 20045939
TI  - Zeolite 4A, a synthetic silicate, suppresses melanogenesis through the
      degradation of microphthalmia-associated transcription factor by extracellular
      signal-regulated kinase activation in B16F10 melanoma cells.
AB  - Zeolite 4A, synthetic silicate, has been shown to exhibit diverse biological
      activities such as anti-cancer and anti-oxidant activity. In the present study,
      we report that the zeolite 4A may improve skin-whitening. We found that zeolite
      4A inhibited melanin production in a dose-dependent manner, which has not
      cytotoxicity. Zeolite 4A also inhibited alpha-melanocyte-stimulating hormone
      (alpha-MSH)-induced melanin synthesis in B16F10 cells. Interestingly, zeolite 4A
      decreased alpha-MSH-induced tyrosinase activity in B16F10 cells, which did not
      inhibit tyrosinase activity under cell-free conditions. The results of this study
      indicate that zeolite 4A may reduce pigmentation by way of an indirect
      nonenzymatic mechanism. We also found that zeolite 4A decreased alpha-MSH-induced
      microphthalmia-associated transcription factor (MITF) and tyrosinase expression
      and that zeolite 4A induced the activation of extracellular signal-regulated
      kinase (ERK). These results suggest that the depigmenting effect of zeolite 4A
      may result from the down-regulation of MITF and tyrosinase expression by
      increasing ERK activity. The results thus provide evidence that zeolite 4A can be
      used as a potential skin-whitening agent.

PMID- 20045940
TI  - Effects of a calcium-channel blocker (CV159) on hepatic ischemia/reperfusion
      injury in rats: evaluation with selective NO/pO2 electrodes and an electron
      paramagnetic resonance spin-trapping method.
AB  - Nitric oxide (NO) and the partial pressure of oxygen (pO(2)) in the liver were
      simultaneously quantified in rats with partial hepatic ischemia/reperfusion
      injury (PHIRI). Real-time NO/pO(2) monitoring and immunohistochemical analysis
      for superoxide dismutase and inducible nitric oxide synthase (iNOS) and
      endothelial NOS (eNOS) were performed to evaluate the protective effects of a
      dihydropyridine-type calcium-channel blocker--CV159--on PHIRI. Serum high
      mobility-group box-1 (HMGB-1) was measured to assess cellular necrosis. Moreover,
      we used in vitro/ex vivo electron paramagnetic resonance spin trapping to assess
      the hydroxyl radical (*OH)-scavenging activity (OHSA) of CV159 and the liver
      tissue. The NO levels were significantly higher in CV159-treated rats than in
      control rats throughout the ischemic phase. Immediately after reperfusion, the
      levels temporarily increased in waves and then gradually decreased in the treated
      rats but remained constant in the control rats. pO(2) was continually higher in
      the treated rats. In these rats, hepatic eNOS expression increased, whereas iNOS
      expression decreased. The treated rats exhibited significantly higher cytosolic
      and mitochondrial concentrations NOx (NO(2)+NO(3)). The serum HMGB-1 levels
      significantly decreased in the treated rats. Moreover, CV159 directly scavenged
      *OH and both mitochondrial and cytosolic OHSA were preserved in the treated rats.
      Thus, CV159-mediated inhibition of intracellular Ca(2+) overloading may
      effectively minimize organ damage and also have *OH-scavenging activity and the
      cytoprotective effects of eNOS-derived NO.

PMID- 20045941
TI  - TJN-419 improves dextran sulfate sodium-induced colitis via inhibition of
      interleukin-12 release.
AB  - We investigated the association of interleukin-12 (IL-12) with development of
      dextran sulfate sodium (DSS)-induced colitis in mice, and examined the effects of
      TJN-419, a synthetic compound derived from acteoside, on this process. Enhanced
      IL-12 production in lipopolysaccharide (LPS)-stimulated macrophages was dose
      dependently inhibited by addition of TJN-419 to culture medium, and this effect
      was abolished by pretreatment with PD98059, an inhibitor of extracellular
      regulated kinase. We then assessed the effect of TJN-419 or a neutralizing
      antibody against murine IL-12 in a DSS-induced colitis model in C57 BL/6 mice.
      Colitis was induced by 5% DSS solution given as drinking water. Treatment with
      the anti-IL-12 antibody was performed intravenously and TJN-419 was administered
      orally. We also investigated the effect of TJN-419 on erosion in the rectum in a
      DSS-induced colitis model in rat. The IL-12 level in the rectum was significantly
      enhanced and the IL-10 level was significantly decreased in animals with DSS
      induced colitis compared with untreated controls. Intravenous injection of the
      anti-IL-12 antibody and oral administration of TJN-419 inhibited clinical
      symptoms in DSS-induced colitis. TJN-419 also inhibited the increase in IL-12 and
      suppressed the area of erosion in the rectum in DSS-induced colitis in rats.
      These results indicate that IL-12 has a possible role in development of DSS
      induced colitis and that TJN-419 is effective for treatment of this disease model
      via inhibition of IL-12 production.

PMID- 20045942
TI  - Authentication of Coscinium fenestratum among the other Menispermaceae plants
      prescribed in Thai folk medicines.
AB  - In Ayurveda and Thai traditional medicines, material from Coscinium fenestratum
      is commonly prescribed as active ingredients with diverse therapeutic purposes.
      However, C. fenestratum is also a seriously endangered medicinal liana. Thus, its
      crude material is very rare and is being substituted with substances from
      Arcangelisia flava or Fibraurea tinctoria (Menispermaceae), which have high
      morphological similarity. In this current study, nuclear 18S ribosomal RNA (rRNA)
      gene and nuclear ribosomal DNA internal transcribed spacer (ITS) gene sequences
      with the polymerase chain reaction-restriction fragment length polymorphisms (PCR
      RFLPs) technique were exploited to identify these three species. The nuclear 18S
      rRNA gene sequences of C. fenestratum, A. flava, and F. tinctoria consisted of
      1809, 1805, and 1809 base pairs (bps), respectively, while their ITS gene regions
      were 694, 622, and 631 bps in length, respectively. The 18S rRNA gene of C.
      fenestratum digested with SmaI restriction enzyme displayed the electrophoresis
      profile of 729 and 790 bps; for A. flava and F. tinctoria, the digested products
      showed fragments of 1519 bps. Although the ITS gene regions of A. flava and F.
      tinctoria had unrecognized sequences with SalI, the SalI-digested ITS of C.
      fenestratum exhibited fragments of approximately 599 bp. Thus, the 18S rRNA gene
      and ITS gene sequences with PCR-RFLPs were proven to be powerful molecular
      markers for identifying C. fenestratum and distinguishing it from the other two
      Menispermaceae plants.

PMID- 20045943
TI  - Evaluation of selective competitive binding of basic drugs to alpha1-acid
      glycoprotein variants.
AB  - We examined the binding of various basic drugs to the F(1)S and A genetic
      variants of alpha(1)-acid glycoprotein (AGP), which were isolated from native
      human commercial AGP (total AGP) by chromatography on an immobilized copper(II)
      affinity adsorbent. The values of the dissociation constant (K(d)) of some basic
      drugs with the F(1)S variant in equilibrium dialysis differed characteristically
      from those with the A variant. The selective binding to these variants was
      evaluated by measuring the displacement ratio of dicumarol bound to the F(1)S
      variant or that of acridine orange bound to the A variant, using circular
      dichroism spectroscopy. There was reasonably good agreement between the K(d)
      values and displacement ratios. There was a characteristic difference between the
      values of inhibition constant (K(i)) of basic drugs towards dipyridamole binding
      to F(1)S and towards disopyramide binding to A in total AGP. We found that the
      K(i) values for dipyridamole binding were well correlated with the K(d) values
      for the F(1)S variant, whereas those for disopyramide binding were well
      correlated with the K(d) values for the A variant. In conclusion, the higher the
      affinity of basic drugs for AGP, the more they inhibit the binding of other basic
      drugs, and further, the inhibitory potency depends on the selectivity of binding
      to the AGP variants.

PMID- 20045944
TI  - Facilitated skin permeation of oregonin by elastic liposomal formulations and
      suppression of atopic dermatitis in NC/Nga mice.
AB  - To develop an external preparation of oregonin (ORG) for the treatment of atopic
      dermatitis (AD), conventional creams (CC) and elastic liposomes (EL) containing
      ORG have been formulated and examined for their in vitro skin permeation
      properties and in vivo therapeutic efficacy assessments. EL, consisting of
      soybean phosphatidylcholine and Tween 80 (85 : 15 w/w %), were of flexible
      nanocarriers: they were about 130 nm in size and had a 4-fold greater
      deformability index than conventional liposomes. In a skin permeation study using
      a Franz diffusion cell mounted with depilated mouse skin, liposomal systems were
      superior to cream, revealing greater flux values. Both CC and EL were diversified
      with the addition of Trans-activating transcriptional activator (Tat) peptide, a
      sort of cell penetrating peptide, and subjected to in vivo efficacy evaluations
      in NC/Nga mice with AD-like lesions. On clinical observation for skin severity,
      rapid and profound improvement was observed in the treatment group with Tat-added
      liposomes (EL/T), showing a significant difference (p<0.05) versus Tat-added
      cream. The results indicated that EL/T treatment is effective for normalizing the
      immune-related responses and alleviating AD, evaluated as changes in the levels
      of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin
      (IL)-4, immunoglobulin E (IgE), and eosinophils in skin or blood.

PMID- 20045945
TI  - Sensitive and real-time method for evaluating corneal barrier considering tear
      flow.
AB  - We developed a new electrophysiological method mimicking tear flow to evaluate
      the epithelial tight junction of rabbit cornea quantitatively. We investigated
      the effect of tear flow on the corneal damage induced by ophthalmic preservatives
      using this method. An Ussing chamber system with Ag/AgCl electrodes was used in
      the electrophysiological experiment. The excised rabbit cornea was mounted in the
      Ussing chamber and the precorneal solution in the chamber was perfused with a
      peristaltic pump at the rate of human tear flow. Corneal transepithelial
      electrical resistance (TEER) was monitored as corneal barrier ability. In the
      electrophysiological method mimicking tear flow, we observed stable TEER, which
      rapidly decreased with benzalkonium chloride (BAC), an eye drop preservative.
      Using this system, we first found that 0.004% BAC decreased corneal TEER
      reversibly. A high concentration of BAC showed strong irreversible damage to the
      tight junction. The influence of BAC on corneal TEER was not only concentration
      dependent but also tear flow rate-dependent. The electrophysiological method
      mimicking tear flow was useful to evaluate the corneal barrier quantitatively.
      Using this method, we clarified that the tear flow was important to protect the
      corneal damage induced by preservatives.

PMID- 20045946
TI  - Investigation of the intestinal permeability and first-pass metabolism of drugs
      in cynomolgus monkeys using single-pass intestinal perfusion.
AB  - To clarify the causes of low oral bioavailability (BA) of drugs in cynomolgus
      monkeys, the experimental method to evaluate the drug permeability and the
      metabolism in the intestine of cynomolgus monkeys was established. An in situ
      intestinal perfusion method was performed with blood sampling from both portal
      and peripheral veins to calculate the intestinal permeability and the metabolism
      of drugs simultaneously. In all experiments, antipyrine was co-perfused with test
      drugs as a non-metabolized reference to calculate the individual portal vein
      blood flow. The effective permeability coefficient (P(eff)) of acetaminophen and
      piroxicam were high, and the fraction of dose absorbed from the gastrointestinal
      tract (Fa) thought to be 1. The intestinal availability (Fg) of acetaminophen and
      piroxicam were calculated to be 0.39 and 1.09, respectively. The Fa*Fg values of
      these drugs calculated from the perfusion study almost coincided with those
      obtained from the in vivo PK analysis in the previous report. In addition, the Fg
      values of verapamil and midazolam were calculated as 0.16 and 0.26, respectively,
      suggesting these drugs were metabolized extensively in the intestine after oral
      administration to cynomolgus monkey. Furthermore, the Fg values of these drugs
      were increased to 0.8-0.85 in the presence of 1-aminobenzotriazole, a typical
      cytochrome P450 (CYP) inhibitor. In conclusion, it was clarified that
      acetaminophen, verapamil and midazolam were metabolized extensively in the
      intestine of cynomolgus monkeys. This intestinal perfusion method is considered
      to be useful to identify the factors of species difference in the oral absorption
      of drugs.

PMID- 20045947
TI  - Preventive effect of green tea catechins on experimental tumor metastasis in
      senescence-accelerated mice.
AB  - Successful avoidance of the immune surveillance system is critical for the
      development of a blood-borne metastasis. Previous findings suggest that
      experimental tumor metastasis was enhanced in senescence-accelerated mice prone
      10 (SAMP10) due to a reduction in immune surveillance potential with age. In the
      present study, water containing green tea (GT)-catechins was freely given to
      SAMP10 mice, and the chemopreventive effect of GT-catechin intake on tumor
      metastasis was examined. Natural killer cell activity, which is an indicator of
      immune surveillance potential and is reduced in control mice with age, was
      maintained by GT-catechin intake. The early accumulation of lung-metastatic
      K1735M2 melanoma cells in lungs after intravenous injection of the cells and
      subsequent experimental lung metastasis was investigated in mice given GT
      catechins. The accumulation at 6 and 24 h after injection of K1735M2 cells was
      significantly suppressed, and the number of lung-metastatic colonies was
      significantly reduced, in comparison with those in control mice. The results
      suggest that GT-catechin intake prevented the experimental tumor metastasis in
      aged SAMP10 mice via its inhibition of a reduction in immune surveillance
      potential with age.

PMID- 20045948
TI  - Inhibitory effects of flavonoid glycosides isolated from the peel of Japanese
      persimmon (Diospyros kaki 'Fuyu') on melanin biosynthesis.
AB  - We found that the acetone extract of the peel of Japanese persimmon (Diospyros
      kaki 'Fuyu') inhibits melanin biosynthesis in mouse B16 melanoma cells. The
      activity-guided purification of the extract resulted in isolation of two active
      compounds, which have been identified as flavonoid glycosides, isoquercitrin
      (quercetin-3-O-glucoside) and hyperin (quercetin-3-O-galactoside) by spectral
      analysis. Isoquercitrin and hyperin strongly inhibited the production of melanin
      (IC(50): 21.7 and 18.2 microM, respectively). The inhibitory effects were found
      to be mediated by suppression of tyrosinase expression.

PMID- 20045949
TI  - In vitro activities of azole antifungal agents against Propionibacterium acnes
      isolated from patients with acne vulgaris.
AB  - The Gram-positive bacterium Propionibacterium acnes is the causative agent of
      acne vulgaris. Antibiotics such as tetracycline and macrolide derivatives are
      used to treat this skin disease; however, the isolation frequency of antibiotic
      resistant P. acnes has been increasing. The anti-P. acnes activity of imidazole
      antifungal agents was reported more than 20 years ago, and since then, new azole
      antifungal agents have been marketed. Thus, this study determined the in vitro
      activities of azole antifungal agents against P. acnes isolated from patients
      with acne vulgaris. Of the five agents tested, miconazole, ketoconazole, and
      itraconazole showed concentration-dependent anti-P. acnes activity, including
      against antibiotic-resistant isolates. Time-kill assay also showed the time
      dependent activity of the drugs. Fluconazole and voriconazole showed no anti-P.
      acnes activity.

PMID- 20045950
TI  - Cafestol, a coffee-specific diterpene, is a novel extracellular signal-regulated
      kinase inhibitor with AP-1-targeted inhibition of prostaglandin E2 production in
      lipopolysaccharide-activated macrophages.
AB  - Coffee is a popular beverage worldwide with various nutritional benefits.
      Diterpene cafestol, one of the major components of coffee, contributes to its
      beneficial effects through various biological activities such as chemopreventive,
      antitumorigenic, hepatoprotective, antioxidative and antiinflammatory effects. In
      this study, we examined the precise molecular mechanism of the antiinflammatory
      activity of cafestol in terms of prostaglandin E(2) (PGE(2)) production, a
      critical factor involved in inflammatory responses. Cafestol inhibited both
      PGE(2) production and the mRNA expression of cyclooxygenase (COX)-2 from
      lipopolysaccharide (LPS)-treated RAW264.7 cells. Interestingly, this compound
      strongly decreased the translocation of c-Jun into the nucleus and AP-1 mediated
      luciferase activity. In kinase assays using purified extracellular signal
      regulated kinase 2 (ERK2) or immunoprecipitated ERK prepared from LPS-treated
      cells in the presence or absence of cafestol, it was found that this compound can
      act as an inhibitor of ERK2 but not of ERK1 and mitogen-activated protein kinase
      kinase 1 (MEK 1). Therefore our data suggest that cafestol may be a novel ERK
      inhibitor with AP-1-targeted inhibitory activity against PGE(2) production in LPS
      activated RAW264.7 cells.

PMID- 20045951
TI  - Inhibition of tumor progression locus 2 protein kinase suppresses receptor
      activator of nuclear factor-kappaB ligand-induced osteoclastogenesis through down
      regulation of the c-Fos and nuclear factor of activated T cells c1 genes.
AB  - Whether tumor progression locus 2 (Tpl2)/cancer Osaka thyroid (Cot) protein
      kinase participates in osteoclastogenesis from receptor activator of nuclear
      factor-kappaB ligand (RANKL)-stimulated monocytes/macrophages remains elusive. To
      clarify this, a selective and potent inhibitor of Tpl2, 1,7-naphtyridine-3
      carbonitrile, was used. When RAW264.7 cells were stimulated with RANKL, Tpl2 was
      found to be activated. Under this condition, the Tpl2 inhibitor suppressed
      osteoclastogenesis in a dose-dependent manner. This was due to the blockade of
      the phosphorylation of mitogen activated protein kinase/ERK kinase (MEK) and
      extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinase
      (JNK) or p38, concomitant with the down-regulation of the c-Fos and nuclear
      factor of activated T cells (NFAT)c1 genes. A long period of RANKL-stimulated
      cell exposure to the inhibitor suppressed osteoclastogenesis as assessed by
      tartrate-resistant acid phosphatase (TRAP) staining and pit formation on dentin
      slices. Almost identical results were obtained with macrophage colony-stimulating
      factor (M-CSF) and RANKL-stimulated bone marrow cells. These findings suggest the
      possibility that Tpl2 plays a pivotal role in osteoclastogenesis and thus that
      its inhibitor is useful for investigating the differentiation of
      monocytes/macrophages to osteoclasts after treatment with RANKL or other stimuli.

PMID- 20045952
TI  - Effect of NIP-142 on potassium channel alpha-subunits Kv1.5, Kv4.2 and Kv4.3, and
      mouse atrial repolarization.
AB  - Effects of NIP-142, a benzopyran compound which terminates experimental atrial
      arrhythmia, on potassium channel alpha-subunits and mouse atrial repolarization
      were examined. NIP-142 concentration-dependently blocked the outward current
      through potassium channel alpha subunits Kv1.5, Kv4.2 and Kv4.3 expressed in
      Xenopus oocytes. In isolated mouse atrial myocardia, NIP-142 prolonged the action
      potential duration and effective refractory period, and increased the contractile
      force. These results suggest that NIP-142 blocks the potassium channels
      underlying the transient and sustained outward currents, which may contribute to
      its antiarrhythmic activity.

PMID- 20045953
TI  - The inhibitory effect of ergosterol, a bioactive constituent of a traditional
      Japanese herbal medicine saireito on the activity of mucosal-type mast cells.
AB  - Mucosal inflammation in ulcerative colitis (UC) is presumed to be regulated
      primarily by type 2 T helper cell immune responses and mucosal mast cells in the
      colon are thought to play an important role in the pathogenesis of the mucosal
      inflammation. Saireito, a Japanese herbal medicine of standardized quality,
      originating from traditional Chinese medicine (Kampo medicine), is composed of
      two different Kampo medicines (shosaikoto and goreisan) and is often used for UC
      in Japan. In this study, we examined the direct effects of these Kampo medicines
      and their constituents on the antigen-induced degranulation of mucosal-type mast
      cells. Mucosal-type murine bone marrow-derived mast cells (mBMMCs) were
      pretreated by these drugs for 24 h, and immunoglobulin E (IgE) receptor-triggered
      degranulation of mBMMCs was assessed by beta-hexosaminidase release. Goreisan
      showed inhibitory effects on degranulation of mBMMCs in a dose-dependent manner.
      Among the five constituent medicinal herbs of goreisan, Poria and Polyporus had
      the inhibitory effects on mBMMCs. Ergosterol, a principal and common component of
      Poria and Polyporus, also suppressed the degranulation of mBMMCs. Our results
      provide a molecular basis to explain a portion of the beneficial therapeutic
      properties of saireito on UC.

PMID- 20045954
TI  - Phosphorylation of signal transducer and activator of transcription 6 (STAT6) and
      STAT1, but not STAT3, induced by antigen inhalation in bronchial smooth muscles
      of sensitized mice.
AB  - The signal transducer and activator of transcription (STAT) family of molecules
      play a critical role in the signaling of many cytokines. In addition to STAT6,
      implication of STAT1 and STAT3 in the development of airway hyperresponsiveness
      (AHR) has also been suggested in allergic bronchial asthma. However, there is
      little information whether or not antigen challenge really causes the in vivo
      activation of these STAT molecules in bronchial smooth muscles (BSMs). In the
      present study, the activations of these STATs were examined in BSMs of mice with
      allergic bronchial asthma. Male BALB/c mice were sensitized and repeatedly
      challenged with ovalbumin (OA) antigen. Total protein samples of the left main
      bronchi were prepared at 3 after the last OA challenge, and Western blot analyses
      for total and tyrosine-phosphorylated STATs molecules were conducted. In addition
      to the phosphorylation of STAT6, a significant increase in the level of
      phosphorylated STAT1 was also observed after the antigen exposure. In contrast,
      no significant increase in the level of phosphorylated STAT3 was observed in this
      mouse model of allergic bronchial asthma. The antigen exposure did not change the
      protein expressions of these STATs themselves. These findings suggest that STAT6
      and STAT1, but not STAT3, might be crucial signal transducers in the development
      of BSM hyperresponsiveness, one of the causes of AHR in asthmatics.

PMID- 20045955
TI  - Effect of chondroitinase on dermatan sulfate-facilitated arginine amidase
      released from rabbit ear artery.
AB  - We examined the effects of chondroitinases on the release of dermatan sulfate
      (DS)-induced arginine amidase (AA) from rabbit ear artery. DS-induced AA release
      was significantly decreased by treatment with chondroitinase ABC (ABCase) in the
      rabbit ear artery. On the other hand, Chondroitinase ACII (ACIIase) enhanced
      spontaneous and DS-induced AA release. Heat-inactivated ABCase and ACIIase did
      not affect spontaneous and DS-induced AA release. Furthermore, ABCase, but not
      ACIIase and heat-inactivated chondroitinases, degraded DS. These results indicate
      that the facilitatory effect of DS-induced AA release from the rabbit ear artery
      is affected by the molecular size of DS.

PMID- 20045956
TI  - The disposition of pravastatin in a rat model of streptozotocin-induced diabetes
      and organic anion transporting polypeptide 2 and multidrug resistance-associated
      protein 2 expression in the liver.
AB  - The combination of diabetes and hyperlipidemia promotes the development of
      atherosclerosis. Therefore, it is important for diabetic patients to control
      blood fat. 3-Hydroxy-3-methylglutaryl enzyme A (HMG-CoA) reductase inhibitors
      (statins), like pravastatin, are frequently administered to diabetic patients for
      this purpose. Although the alterations of metabolic enzymes and transporters in
      the diabetic liver maybe change the disposition of pravastatin, the effect has
      not been fully investigated. In the present study, we investigated the
      disposition of pravastatin and the mRNA expression of transporters in the liver.
      Pravastatin (5 mg.kg(-1) body weight) was administered intravenously to diabetic
      rats, and the pravastatin concentrations in the plasma, urine, and bile were
      measured by high-performance liquid chromatography. Changes in the mRNA
      expressions of multidrug resistance-associated protein 2 (MRP2) and organic anion
      transporting polypeptide 2 (OATP2) in the liver were also estimated using reverse
      transcriptase-polymerase chain reaction (RT-PCR). We found that the plasma
      pravastatin concentration was lower in the diabetic rat because the
      transportation of pravastatin into hepatocytes was promoted along with increased
      expression of OATP2. The biliary excretion ratio of pravastatin was significantly
      lower in the diabetic rat because the pravastatin transportation into bile was
      reduced along with the decreased expression of MRP2. To clarify these phenomena,
      the analysis of mRNA expression using real-time PCR and the measurement of the
      amount and the activity of proteins are necessary in future study.

PMID- 20045957
TI  - Method for predicting homology modeling accuracy from amino acid sequence
      alignment: the power function.
AB  - We have devised a power function (PF) that can predict the accuracy of a three
      dimensional (3D) structure model of a protein using only amino acid sequence
      alignments. This Power Function (PF) consists of three parts; (1) the length of a
      model, (2) a homology identity percent value and (3) the agreement rate between
      PSI-PRED secondary structure prediction and the secondary structure judgment of a
      reference protein. The PF value is mathematically computed from the execution
      process of homology search tools, such as FASTA or various BLAST programs, to
      obtain the amino acid sequence alignments. There is a high correlation between
      the global distance test-total score (GDT_TS) value of the protein model based
      upon the PF score and the GDT_TS(MAX) value used as an index of protein modeling
      accuracy in the international contest Critical Assessment of Techniques for
      Protein Structure Prediction (CASP). Accordingly, the PF method is valuable for
      constructing a highly accurate model without wasteful calculations of homology
      modeling that is normally performed by an iterative method to move the main chain
      and side chains in the modeling process. Moreover, a model with higher accuracy
      can be obtained by combining the models ordered by the PF score with models
      sorted by the size of the CIRCLE score. The CIRCLE software is a 3D-1D program,
      in which energetic stabilization is estimated based upon the experimental
      environment of each amino acid residue in the protein solution or protein
      crystals.

PMID- 20045958
TI  - Thermal reversible microemulsion system for poorly water-soluble YH439 for oral
      delivery.
AB  - To improve bioavailability of poorly water-soluble YH439, a thermal reversible
      microemulsion system was prepared using modified fatty acids such as capric acid
      and palmitic acid with PEG 400. A combination of Capric-PEG 400 and Palmitic-PEG
      400 with a ratio of 1 : 3 used as a lipid matrix and Cremophor RH40 and Neobee M
      5 were selected as an oil and a surfactant, respectively. The microemulsion with
      melting point of 36.5 degrees C was produced by mixing the lipid matrices,
      Cremophor RH40 and Neobee M-5 with a volume ratio of 5 : 4 : 1. After the
      microemulsion was dispersed in the aqueous medium, the average particle size of
      28 nm was obtained. At the release measurements of YH439 after 45 min suspension
      in pH 1.2 aqueous medium, about 80%, 65%, 10% and less than 5% of drug were
      released from the thermal reversible microemulson, Gelucire formulation, 5% Ca
      carboxymethylcellulose (CMC) suspension and YH439 powder, respectively. The
      apparent permeability of YH439 in microemulsion either from apical to basolateral
      or basolateral to apical after measuring YH439 across a Caco-2 cell monolayer in
      a Transwell larger than Gelucire formulation or 5% Na-CMC suspension. The area
      under the drug concentration-time curves (AUC) and maximal blood concentration
      (C(max)) after oral administration of YH439 loaded on thermal reversible
      microemulsion were significantly increased than drug loaded on either Gelucire
      formulation or 5% Na-CMC suspension. Thus, the present work demonstrates that the
      thermal reversible microemulsion system of YH439 greatly enhances the
      bioavailability of YH439 after oral administration due to the improvement of
      solubility and dispersion of the drug in the artificial gastrointestinal tract
      without pepsin.

PMID- 20045960
TI  - Electrochemical oxidation of catechols in the presence of phenyl-Meldrum's acid.
      Synthesis and kinetic evaluation.
AB  - Electrochemical oxidation of catechols in the presence of phenyl-Meldrum's acid
      as a nucleophile in aqueous solution has been studied in detail by means of
      cyclic voltammetry and controlled potential coulometry. The results indicate that
      the o-benzoquinone derived from catechols participates in Michael addition
      reaction with phenyl-Meldrum's acid to form corresponding products. We derived
      some new "highly oxygenated compounds with catechol ring" with good yields based
      on electrochemical oxidation in the controlled potential condition in aqueous
      solutions, without toxic reagents and solvents at carbon electrode in an
      undivided cell, using an environmentally friendly method. Furthermore, the
      observed homogeneous rate constants (k(obs)) of the chemical reaction between o
      benzoquinone and phenyl-Meldrum's acid were estimated by comparing the
      experimental cyclic voltammetric curves with the digitally simulated ones.

PMID- 20045959
TI  - An improved formulation screening and optimization method applied to the
      development of a self-microemulsifying drug delivery system.
AB  - This study focused on the development of an improved formulation screening and
      optimization method for a self-microemulsifying drug delivery system (SMEDDS).
      Solubility study and construction of a ternary phase diagram were carried out to
      determine the primary formulation components. Experimental design combined with a
      desirability study was employed to obtain the optimal formulation composition.
      The obtained bufalin SMEDDS formulation was Maisine 35-1 and Miglyol 812N (1 : 1,
      w/w) of 29.5%, Cremophor EL of 39.5%, and Transcutol P of 30.5%. It showed
      desired properties with droplet size of 33.9 nm; polydispersity index of 0.126;
      equilibrium solubility of 12.6 mg/ml, and 73.6% of soluble drug post-digestion. A
      rapid release of up to 21% occurred in the first 10 min. A bufalin SMEDDS was
      well absorbed at all intestinal segments. The absorption of bufalin from a SMEDDS
      was 2.38-fold higher than that of bufalin suspension in terms of relative
      bioavailability. The studies on solubility and ternary phase diagrams combined
      with experimental design may offer a valuable and efficient strategy for
      developing and optimizing a SMEDDS to obtain optimal formulations with desired
      characteristics.

PMID- 20045961
TI  - Syntheses of carnosic acid and carnosol, anti-oxidants in Rosemary, from
      pisiferic acid, the major constituent of Sawara.
AB  - Carnosic acid (2), a major anti-oxidant in rosemary (Rosmarinus officinalis), was
      synthesized from pisiferic acid (1), the major constituent of Sawara
      (Chamaecyparis pisifera), via ortho-oxidation of the phenol using meta
      chlorobenzoyl peroxide (mCBPO), chloroacetyl meta-chlorobenzoyl peroxide
      (CAMCBPO) or 2-iodoxybenzoic acid (IBX). Carnosol (3), another anti-oxidant in
      rosemary, was synthesized from carnosic acid by oxidation with silver oxide.
      Potent antibacterial activities against Propionibacterium acnes (ATCC 6919)
      (minimum inhibitory concentration (MIC) mug/ml) and Staphylococcus aureus
      ME/GM/TC Resistant (ATCC 33592) (MIC mug/ml) of carnosic acid and carnosol were
      reported.

PMID- 20045962
TI  - Paralemnolins J-P, new sesquiterpenoids from the soft coral Paralemnalia
      thyrsoide.
AB  - Six new sesquiterpenoids, paralemnolins J-O (1-6), along with one novel
      norsesquiterpenoid, paralemnolin P (7), have been isolated from the soft coral
      Paralemnalia thyrsoides. The structures of metabolites 1-7 were established on
      the basis of extensive NMR study and chemical methods. The structure of 5 was
      further confirmed by a single-crystal X-ray analysis. Cytotoxicity of these
      metabolites toward a limited panel of cancer cell lines also is described.

PMID- 20045963
TI  - Evaluation of correlation between dissolution rates of loxoprofen tablets and
      their surface morphology observed by scanning electron microscope and atomic
      force microscope.
AB  - We observed the surface morphological structures of 60 mg tablets of Loxonin,
      Loxot, and Lobu using scanning electron microscope (SEM) and atomic force
      microscope (AFM) to evaluate the dissolution rates. We found a significant
      difference among the initial dissolution rates of the three kinds of loxoprofen
      sodium tablets. Petal forms of different sizes were commonly observed on the
      surface of the Loxonin and Loxot tablets in which loxoprofen sodium was confirmed
      by measuring the energy-dispersible X-ray (EDX) spectrum of NaKalpha using SEM.
      However, a petal form was not observed on the surface of the Lobu tablet,
      indicating differences among the drug production processes. Surface area and
      particle size of the principal ingredient in tablets are important factors for
      dissolution rate. The mean size of the smallest fine particles constituting each
      tablet was also determined with AFM. There was a correlation between the initial
      dissolution rate and the mean size of the smallest particles in each tablet.
      Visualizing tablet surface morphology using SEM and AFM provides information on
      the drug production processes and initial dissolution rate, and is associated
      with the time course of pharmacological activities after tablet administration.

PMID- 20045964
TI  - Design and synthesis of peptidomimetic factor VIIa inhibitors.
AB  - Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as
      a promising target for developing new anticoagulant drugs. In previous reports,
      we described a S3 subsite found in the X-ray crystal structure of compound 2 that
      bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure
      information and with the aim of improving the inhibition activity for FVIIa/TF
      and selectivity against other serine proteases, we synthesized derivatives by
      introducing substituents at position 5 of the indole ring of compound 2. Among
      them, compound 16 showed high selectivity against other serine proteases.
      Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray
      structure analysis revealed that compound 16 improved selectivity by forming
      hydrogen bonds with Gln217, Thr99 and Asn100.

PMID- 20045965
TI  - Development of sarpogrelate external preparation for intractable pain control. I.
      Pre-formulation study on application of modified beta-cyclodextrins.
AB  - To optimize the formulation of in-hospital sarpogrelate (SPG) preparation for
      external use, various cyclodextrins (CDs) were investigated for their ability to
      improve the aqueous solubility and chemical stability of SPG. Although hydrolysis
      of SPG was markedly accelerated at above pH 7.0 in aqueous solution, the addition
      of modified beta-CD resulted in suppressed SPG hydrolysis. Addition of
      sulfobutylether-beta-CD (SBE-beta-CD, Captisol had the most significant
      stabilization effect. Phase solubility diagram and (1)H-NMR analyses indicated
      that dimethyl-beta-CD and SBE-beta-CD formed significantly stable inclusion
      complexes with SPG in aqueous solution, thereby contributing to both the
      increased solubility and chemical stabilization of SPG. In terms of the clinical
      safety of CD derivatives, SBE-beta-CD was determined to be the most suitable
      solubilizing agent for external SPG preparation.

PMID- 20045966
TI  - Effects of compression and grinding on chemical stability of a benzodiazepine
      receptor agonist.
AB  - SX-3228, 6-benzyl-3-(5-methoxy-1,3,4-oxadiazol-2-yl)-5,6,7,8-tetrahydro-1,6
      naphthyridin-2(1H)-one, is a newly synthesized benzodiazepine receptor agonist
      intended to be developed as a tablet preparation. However, it was found that the
      drug substance was remarkably chemically unstable in tablet form compared to the
      powder mixture for tableting. Chemical destabilization due to compression also
      occurred in the drug substance alone. After investigating the cause of the
      destabilization, powder X-ray diffraction analysis showed that the crystallinity
      of the drug substance decreased depending on the extent of mechanical treatments
      such as compression and grinding. In thermal analysis it became evident that the
      exothermic peaks due to degradation clearly broadened and shifted toward lower
      temperatures by these mechanical treatments. It was then revealed that the
      degradation temperature decreased and the amount of degradation products after
      storage increased with decreasing crystallinity, even though there was little
      change in the amount of degradation products shortly after mechanical treatments.
      These results demonstrated that the drug substance became chemically unstable
      with decreasing crystallinity. It was proved that chemical instability of the
      drug substance in the tablet preparation was due to decreasing crystallinity
      caused by compression. It would therefore be difficult to produce chemically
      stable tablets containing this compound using a conventional manufacturing
      process. Tablets for this compound should be prepared without mechanical
      treatments such as compression and grinding.

PMID- 20045967
TI  - Four new ent-kauranoids from Isodon rubescens var. lushanensis and data
      reassignment of dayecrystal B.
AB  - Four new 7, 20-epoxy-ent-kauranoids, rubluanins A-D (1-4) and eleven known ones,
      were isolated from Isodon rubescens var. lushanensis, and their structures were
      elucidated by spectroscopic analysis. Compounds 2-14 were evaluated for their
      cytotoxicity in several human tumor cell lines (U937, Jurkat, HL-60, K562,
      SGC790, and HepG2). Among the compounds, lasiokaurin (13) showed significant
      cytotoxic activity of 0.62 microM (IC(50)) in U937 cells.

PMID- 20045968
TI  - Anti-inflammatory principles from the stem and root barks of Citrus medica.
AB  - Bioassay-guided investigation of the anti-inflammatory principles from the stem
      and root barks of Citrus medica L. var. sarcodactylis SWINGLE has led to the
      isolation of a new coumarin, namely citrumedin-B (1) and thirty known compounds.
      The anti-inflammatory components were xanthyletin (2), nordentatin (3),
      atalantoflavon (4) and lonchocarpol A (5) which displayed potent nitric oxide
      (NO)-reducing activity in microglial cells. The structure of this new compound
      was completely elucidated using a combination of 2D NMR techniques (correlation
      spectroscopy (COSY), nuclear Overhauser effect spectroscopy (NOESY),
      heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond
      connectivity (HMBC)) and HR-electrospray ionization (ESI)-MS analyses. The known
      compounds were identified by comparison of their spectroscopic and physical data
      with those reported in the literature. These results can be inferred from the
      treatment of allergic response and inflammatory properties of Citrus medica L.
      var. sarcodactylis SWINGLE in traditional Chinese medicine.

PMID- 20045969
TI  - HUMAN FAMSD-BASE: high quality protein structure model database for the human
      genome using the FAMSD homology modeling method.
AB  - Almost all proteins express their biological functions through the structural
      conformation of their specific amino acid sequences. Therefore, acquiring the
      three-dimensional structures of proteins is very important to elucidate the role
      of a particular protein. We had built protein structure model databases, which is
      called RIKEN FAMSBASE (http://famshelp.gsc.riken.jp/famsbase/). The RIKEN
      FAMSBASE is a genome-wide protein structure model database that contains a large
      number of protein models from many organisms. The HUMAN FAMSBASE that is one part
      of the RIKEN FAMSBASE contains many protein models for human genes, which are
      significant in the pharmaceutical and medicinal fields. We have now implemented
      an update of the human protein modeling database consisting of 242918 constructed
      models against the number of 20743 human protein sequences with an improved
      modeling method called Full Automatic protein Modeling System Developed (FAMSD).
      The results of our benchmark test of the FAMSD method indicated that it has an
      excellent capability to pack amino acid side-chains with correct torsion angles
      in addition to the main-chain, while avoiding the formation of atom-atom
      collisions that are not found in experimental structures. This new protein
      structure model database for human genes, which is named HUMAN FAMSD-BASE, is
      open to the public as a component part of the RIKEN FAMSBASE at
      http://mammalia.gsc.riken.jp/human_famsd/. A significant improvement of the HUMAN
      FAMSD-BASE in comparison with the preceding HUMAN FAMSBASE was verified in the
      benchmark test of this paper. The HUMAN FAMSD-BASE will have an important impact
      on the progress of biological science.

PMID- 20045970
TI  - A novel analytical method for pharmaceutical polymorphs by terahertz spectroscopy
      and the optimization of crystal form at the discovery stage.
AB  - A novel analytical method for the determination of pharmaceutical polymorphs was
      developed using terahertz spectroscopy. It was found out that each polymorph of a
      substance showed a specific terahertz absorption spectrum. In particular,
      analysis of the second derivative spectrum was enormously beneficial in the
      discrimination of closely related polymorphs that were difficult to discern by
      powder X-ray diffractometry. Crystal forms that were obtained by crystallization
      from various solvents and stored under various conditions were specifically
      characterized by the second derivative of each terahertz spectrum. Fractional
      polymorphic transformation for substances stored under stressed conditions was
      also identified by terahertz spectroscopy during solid-state stability test, but
      could not be detected by powder X-ray diffractometry. Since polymorphs could be
      characterized clearly by terahertz spectroscopy, further physicochemical studies
      could be conducted in a timely manner. The development form of compound examined
      was determined by the results of comprehensive physicochemical studies that
      included thermodynamic relationships, as well as chemical and physicochemical
      stability. In conclusion, terahertz spectroscopy, which has unique power in the
      elucidation of molecular interaction within a crystal lattice, can play more
      important role in physicochemical research. Terahertz spectroscopy has a great
      potential as a tool for polymorphic determination, particularly since the second
      derivative of the terahertz spectrum possesses high sensitivity for
      pharmaceutical polymorphs.

PMID- 20045971
TI  - Novel synthesis of ureas: application of t-butylureas.
AB  - Otherwise inaccessible tropolonylureas were prepared by reaction of t-butylurea
      with appropriate amines, with elimination of t-butylamine. This method is also
      generally applicable for urea synthesis.

PMID- 20045972
TI  - Development and application of a solution-phase automated synthesizer,
      'ChemKonzert'.
AB  - In this paper we describe the development of a fully-automated solution-phase
      synthesizer, 'ChemKonzert' that can be used to prepare a wide variety of organic
      compounds. The automated synthesizer is ingeniously designed to perform most of
      the chemical reactions currently used by synthetic organic chemists and utilizes
      a centrifugal separator to efficiently achieve liquid-liquid extraction. The
      design of the hardware and software will be described in this paper, and several
      examples of organic reactions will also be presented as applications of the
      apparatus.

PMID- 20045973
TI  - Synthesis, antitumor evaluation and crystal structure of hydroxyurea derivatives.
AB  - A series of hydroxyurea derivatives have been synthesized and elucidated by means
      of FT-IR, (1)H-, (13)C-NMR and MS. The exact stereostructures of representative
      compounds have been determined by X-ray crystal structure analysis. In the
      crystals, inversion dimers linked by pairs of N-H...O hydrogen bonds occurred,
      and further N-H...O links led to chains of molecules. In vitro antitumor
      activities against Tca8113 human tongue cancer cells and L1210 murine leukemia
      cells were evaluated. A total of 8 of the 12 compounds had higher inhibitory
      activities than hydroxyurea against L1210 cells. Among them, the most promising
      compounds were 3e, 3d, 3a and 2d.

PMID- 20045974
TI  - Structural characteristics for superoxide anion radical scavenging and productive
      activities of green tea polyphenols including proanthocyanidin dimers.
AB  - The purpose of this paper is to report structural characteristics for superoxide
      anion radical (O(2(-))) scavenging and productive activities of green tea
      polyphenols. (-)-Epicatechin 3-O-gallate (5), (-)-epigallocatechin (6), (-)
      epigallocatechin 3-O-gallate (7), (+)-gallocatechin-(4alpha-->8')
      epigallocatechin (8), and (-)-epigallocatechin-(2beta-->O-->7', 4beta-->8')
      epicatechin 3'-O-gallate (9) were isolated from the tea plant Camellia sinensis
      L. (+)-Epigallocatechin-(2beta-->O-->7, 4beta-->8')-epicatechin (10) was prepared
      by hydrolyzing 9. The polyphenols, as well as commercially available pyrogallol
      (1), methyl gallate (2), (+)-catechin (3), (-)-epicatechin (4), and the flavonol
      myricetin (11), produced O(2(-)) in descending order 1, 6 asymptotically equal
      to11 asymptotically equal to8, 7, 10, 2 asymptotically equal to9, 5
      asymptotically equal to4. In the polyphenols with the pyrogallol-type B-ring
      and/or galloyl group, electron-withdrawing substituents (carbonyl and ketal
      carbons) and/or intramolecular hydrogen bonding constituted structural
      characteristics against the autoxidation reaction. The O(2(-))-productive
      activity partially counteracted O(2(-))-scavenging activity. However, such
      structural characteristics appeared to enhance the scavenging activity,
      accordingly the polyphenols in effect served as O(2(-))-scavengers in descending
      order 9 asymptotically equal to7, 2, 11, 8, 10, 3 asymptotically equal to4. On
      the other hand, 6, having no such structural characteristic, acted as a O(2(-))
      generator, as well as 1. Further assessments covering tannins (e.g., A-type
      proanthocyanidin dimer 9) are needed to identify which green tea polyphenols are
      the most desirable chemopreventive agents.

PMID- 20045975
TI  - L-lysine pro-prodrug containing trans-ferulic acid for 5-amino salicylic acid
      colon delivery: synthesis, characterization and in vitro antioxidant activity
      evaluation.
AB  - In the present work, we report the synthesis of a new 5-amino salicylic acid (5
      ASA) pro-prodrug, useful in Crohn disease treatment, and the evaluation of its
      antioxidant activity. Using as pharmacological carrier L-lysine amino acid and
      taking advantage of its intrinsic chemical reactivity, due to the presence of two
      amino groups, placed on the chiral center and in epsilon-position, we inserted
      trans-ferulic acid in epsilon-position, through amidation reaction, esterified
      with methanol the carboxylic group and, finally, submitted the free amino group
      to diazotation with 5-ASA, principal drug for inflammatory bowel diseases (IBD)
      care. All intermediates of synthesis and the final product (derivative A) were
      characterized with usual spectroscopic techniques, as FT-IR, GC/MS and (1)H-MNR.
      Finally, the derivative A antioxidant activity in inhibiting the lipid
      peroxidation, in rat-liver microsomal membranes, induced in vitro by two
      different sources of free radicals, 2,2'-azobis (2-amidinopropane) (AAPH) and
      tert-butyl hydroperoxide (tert-BOOH), was evaluated. Our pro-prodrug could be
      successfully applied in pharmaceutical field both as prodrug of 5-ASA than as
      carrier of trans-ferulic acid.

PMID- 20045976
TI  - Negative and positive ion mode LC/MS/MS for simple, sensitive analysis of sorbic
      acid.
AB  - Sorbic acid (SA: CH(3)-CH=CH-CH=CH-COOH) is one of the widely used food
      preservatives, although there have been some reports of its toxic activity, for
      example, on DNA and skin cells. In order to examine the effects of SA on
      mammalian tissues, we have developed a highly sensitive analytical method using
      LC/MS/MS with positive and negative ion mode electrospray ionization (ESI). In a
      previous study, we found that a nonacidic eluent offers better ionization
      efficiency than acids or their ammoniun salts. However, optimal results could not
      be obtained because the anion form of SA is poorly retained on a conventional
      reversed phase column. To resolve this problem, we chose a new type of column and
      used high-resolution mass spectrometry and positive ion mode analysis. There have
      only been a few reports using these methods in the positive mode, for example
      derivatized SA, because acid compounds such as SA are usually used in the
      negative ion mode. However, a new type of low-carbon-content and polar-endcapped
      C18 phase column was developed for better separation of SA from the matrix. High
      resolution selected reaction monitoring (SRM) gave the best signal to noise ratio
      in normal-resolution SRM. In the positive ion mode, the CH(3)OH-0.05% HCOOH/0.1%
      CH(3)COOH eluent system yielded the best ionization efficiency. We propose a
      highly sensitive and simple analysis using a two-ion-mode ESI SRM method. Such
      systems should allow quantification of the amount of SA in or around the cells,
      without the need for pretreatment such as solid phase extraction.

PMID- 20045977
TI  - Synthesis and configurational stability of (S)- and (R)-deuteriothalidomides.
AB  - 3'-Deuteriothalidomide was synthesized and found to be configurationally five
      times more stable than thalidomide toward racemization at physiological pH.

PMID- 20045978
TI  - Vibralactones D-F from cultures of the basidiomycete Boreostereum vibrans.
AB  - Three new metabolites, vibralactones D-F (1-3) were isolated from cultures of the
      basidiomycete Boreostereum vibrans. The relative configuration of 1 was
      established on the basis of X-ray diffraction analysis, while the absolute
      configurations of 1-3 were assigned using a modified Mosher's method. Compound 1
      showed weak inhibitory activities against isozymes of 11beta-hydroxysteroid
      dehydrogenases (HSD) with IC(50) values of 85.7 microM (human HSD1), 295.2 microM
      (mouse HSD1), and 87.1 microM (human HSD2).

PMID- 20045979
TI  - Selective detection of hydroxyl radical scavenging capacity based on
      electrogenerated chemiluminescence detection using tris(2,2'
      bipyridine)ruthenium(III) by flow injection analysis.
AB  - We describe a new method for detecting hydroxyl radical scavenging capacity based
      on tris(2,2'-bipyridine)ruthenium(III) [Ru(bpy)(3)(3+)] chemiluminescence and
      flow injection analysis. Hydroxyl radicals were generated by the Fenton reaction.
      The scavenging capacity of the six antioxidants tested decreased in the following
      order: edaravone>L-tryptophan>gallic acid>Trolox>N-acetyl-L-cysteine>ascorbic
      acid. The proposed method allowed a sample throughput of about 80 samples/h. The
      six antioxidants were found to inhibit chemiluminescence intensity of
      Ru(bpy)(3)(2+). The proposed method is a rapid, selective, and accurate procedure
      for the study of hydroxyl radical scavenging capacity by Ru(bpy)(3)(3+)
      chemiluminescence.

PMID- 20045980
TI  - Triterpenoids from Camellia japonica and their cytotoxic activity.
AB  - From the ethyl acetate fraction of the stem bark of Camellia japonica, three new
      triterpenoids, 3beta-O-acetyl-16beta-hydroxy-12-oxoolean (6), 3beta-O-acetyl
      16beta-hydroxy-11-oxoolean-12-ene (7), and 3beta-O-acetyl-16beta-hydroxyolean-12
      ene (8), along with seven known compounds, 3alpha-hydroxy-1-oxofriedelan (1),
      friedelin (2), 3beta-friedelanol (3), canophyllol (4), 3-oxofriedelan-1(2)-ene
      (5), beta-amyrin (9), camellenodiol (10), and camelledionol (11) were isolated.
      Their structures were established on the basis of spectroscopic analysis and
      chemical evidence. The isolated compounds were tested in vitro for their
      cytotoxic activities against the A549, LLC, HL-60 and MCF-7 cancer cell lines.
      Among them, compound 8 showed cytotoxicity against LLC and HL-60 cancer cell
      lines with IC(50) values of 25.2 and 21.7 microM, respectively.

PMID- 20045981
TI  - Two new guaiane-type sesquiterpene glycosides from the fruits of Daucus carota L.
AB  - Two new guaiane-type sesquiterpene glycosides, 11-O-acetyl-torilolone 8-O-beta-D
      glucopyranoside (1) and 1beta-hydroxytorilolone 11-O-beta-D-glucopyranoside (2),
      were isolated from the fruits of Daucus carota L. Their chemical structures were
      elucidated on the basis of MS, NMR spectroscopic analyses coupled with chemical
      degradation.

PMID- 20045982
TI  - Identification of binding proteins of fusarielin A as actin and tubulin.
AB  - Fusarielin A (FSA), isolated from culture of Fusarium sp. K432, has anti
      fungal/anti-angiogenic activity. Based on our previous structure-activity
      relationship studies, we prepared FSA-immobilized affinity gel. The results of
      affinity chromatography with this gel indicated that tubulin and actin are FSA
      binding proteins. The binding affinities of tubulin and actin for FSA were
      estimated by the use of surface plasmon resonance spectroscopy.

PMID- 20045984
TI  - Inhibitory effects of Kampo medicine on human UGT2B7 activity.
AB  - Kampo medicine is traditional Japanese medicine modified from the Chinese
      original. Kampo medicine is a mixture of several medicinal herbs and includes
      many ingredients such as glycosides. Glycosides are hydrolyzed to aglycons by
      intestinal bacterial flora and absorbed into the body. Aglycons such as baicalein
      and glycyrrhetinic acid can be conjugated by UDP-glucuronosyltransferase (UGT) in
      human liver or small intestine. UGT2B7 is one of the major isoforms responsible
      for drug conjugation including morphine 3- and 3'- azido-3'-deoxythymidine (AZT)
      glucuronidation. The present study investigates the effects of 51 Kampo
      medicines, 14 medicinal herbs and 11 ingredients on UGT2B7 activity in human
      liver microsomes. Morphine 3-glucuronidation was inhibited by more than 50% by 9
      of 51 Kampo medicines such as Ryo-kei-jutsu-kan-to. AZT glucuronidation was
      inhibited by more than 50% by 24 of 51 Kampo medicines such as Jumi-haidoku-to.
      Medicinal herbs such as Daio (Rhei Rhizoma), Kanzo (Glycyrrhizae Radix) and Keihi
      (Cinnamomi Cortex) exhibited more than 80% inhibition on both glucuronidations.
      The major ingredients of these medicinal herbs inhibited UGT2B7 activity with low
      K(i). Kampo medicines were found to inhibit the UGT2B7 activity and may cause
      drug interactions via the inhibition of UGT.

PMID- 20045985
TI  - Prediction of drug-drug interactions based on time-dependent inhibition from high
      throughput screening of cytochrome P450 3A4 inhibition.
AB  - A method of assessing the risk of drug-drug interaction (DDI) caused by mechanism
      based inhibition (MBI) was developed for early-stage drug development using
      cytochrome P450 (CYP) 3A4 inhibition screening data. CYP3A4 inhibition was
      evaluated using a fluorescent substrate with or without preincubation containing
      an inhibitor. The results showed that five well-known mechanism-based inhibitors,
      but not the competitive inhibitor ketoconazole, had lower IC(50) after
      preincubation, suggesting the utility of the IC(50) shift by preincubation to
      discern mechanism-based inhibitors. A method to approximately predict the change
      in the area under the concentration-time curve (AUC) of a co-administered drug by
      MBI was found using IC(50) shift data and the unbound mean plasma concentration
      of the inhibitor. From our predictions of change in the AUC for 38 drugs using
      this method, all mechanism-based inhibitors causing change in the AUC of more
      than 200% were predicted to be high risk. In conclusion, our method provides a
      simple assessment of the risk of DDI from mechanism-based inhibitors, especially
      in the early stages of drug development.

PMID- 20045986
TI  - Biotransformation profiling of [(14)C]ixabepilone in human plasma, urine and
      feces samples using accelerator mass spectrometry (AMS).
AB  - Ixabepilone (BMS-247550, Ixempra is a semi-synthetic analog of the natural
      product epothilone B and marketed for its use in the treatment of cancer. A
      conventional human ADME study using decay counting methods for (14)C detection
      could not be conducted due to the radiolytic instability of [(14)C]ixabepilone at
      a typical specific activity (generally 1-10 microCi/mg). However,
      [(14)C]ixabepilone was sufficiently stable at low specific activity (1-2 nCi/mg).
      These low levels required the use of accelerator mass spectrometry (AMS) for
      radioactivity detection. The metabolic fate of this compound was investigated in
      eight patients following single intravenous doses of [(14)C]ixabepilone (70 mg,
      80 nCi; specific activity: 1.14 nCi/mg). Metabolite profiles in pooled urine,
      feces and plasma samples were determined by HPLC-AMS analysis. The major
      radioactive component in urine and plasma was [(14)C]ixabepilone. Feces had a
      small amount of ixabepilone. There were numerous other drug-related components in
      both urine and fecal extracts (each <6% of the administered dose). LC/MS analysis
      of plasma, urine and feces samples showed the presence of three degradants of
      ixabepilone and several oxidative metabolites (M+16, M+14 and M-2 metabolites).
      This study demonstrates the utility of AMS in investigating the metabolite and
      excretion profiles of [(14)C]ixabepilone following administration to humans.

PMID- 20045987
TI  - Identification of human UDP-glucuronosyltransferase isoforms responsible for the
      glucuronidation of glycyrrhetinic acid.
AB  - Glycyrrhetinic acid, the active metabolite of glycyrrhizin, is primarily
      eliminated by glucuronidation reaction in vivo. In spite of the widespread
      clinical use of glycyrrhizin, UDP-glucuronosyltransferase (UGT) isoforms involved
      in the glucuronidation of this drug are still unknown. This report identifies and
      characterizes the UGT isoforms responsible for glycyrrhetinic acid
      glucuronidation. In the enzymatic kinetic experiment performed with pooled human
      liver microsomes (HLMs), K(m) was 39.4 microM and V(max) was 609.2 pmol/min/mg
      protein. Of the baculosomes expressing 12 recombinant UGTs investigated, UGT1A1,
      1A3, 2B4 and 2B7 showed catalytic activity and UGT1A3 exhibited the highest
      activity. K(m) values of recombinant UGT1A3 and 2B7 were 3.4 and 4.4 microM,
      respectively. Both imipramine (typical substrate of UGT1A3 and 1A4) and
      flurbiprofen (typical substrate of UGT2B7) inhibit the glucuronidation of
      glycyrrhetinic acid. Estimated IC(50) values were 138 microM for flurbiprofen and
      207 microM for imipramine in the inhibition of the glucuronidation of
      glycyrrhetinic acid in HLMs. These results suggest that glycyrrhetinic acid
      glucuronidation is primarily mediated by UGT1A1, 1A3, 2B4 and 2B7.

PMID- 20045988
TI  - mRNA expression of MDR1 and major metabolising enzymes in human fetal tissues.
AB  - Metabolising enzymes and transport proteins are largely expressed in human
      tissues. They have major impact on drug disposition and effects. We studied mRNA
      expression of phase I and II metabolising enzymes and transporters in fetal
      tissues at different development stages. Hepatic, duodenal, renal and
      neurological fetal tissues were studied at 15, 27 and 42 weeks gestation and mRNA
      expression of 84 enzymes and transporters was analysed by with the RT(2) Profiler
      PCR array system. There was wide variability in gene expression between different
      samples. Independently from age, the highest expression levels were observed in
      the liver and the lowest in the brain for the majority of genes tested. There was
      significant increase in gene expression with age in duodenal and hepatic tissues.

PMID- 20045989
TI  - Influence of the genetic polymorphisms in the 5' flanking and exonic regions of
      CYP2C19 on proguanil oxidation.
AB  - CYP2C19 is a polymorphic enzyme which metabolizes several clinically important
      drugs including proguanil. Variation in the 5' regulatory region may influence
      CYP2C19 activity. This study evaluates the relationship between proguanil
      metabolic ratio and genetic variations of CYP2C19 in a South Indian population.
      Fifty unrelated healthy subjects were genotyped for CYP2C19 (*)2 and (*)3 alleles
      and the 5' flanking region of CYP2C19 was sequenced. Plasma concentrations of
      proguanil and cycloguanil were estimated by reverse phase HPLC after single oral
      doses (200 mg) of proguanil. In silico docking analysis of transcription factors
      binding to its sites in CYP2C19 5' regulatory region was performed. The mean
      metabolic ratios (proguanil/cycloguanil) were highest in (*)1/(*)2 or (*)1/(*)3
      subjects and in (*)2/(*)2 or (*)2/(*)3 as compared to (*)1/(*)1 subjects.
      Subjects with promoter region variation -98T>C showed decrease in the metabolic
      ratios irrespective of other variation, which may explain the deviation from the
      genotype-phenotype association of CYP2C19. In silico analysis predicted
      alteration in the interaction of transcription factors to their binding sites in
      the presence of variant alleles. The results of this study would be useful in
      predicting interindividual differences in the metabolism of substrates of
      CYP2C19.

PMID- 20045990
TI  - Bonitos with low content of malodorous trimethylamine as palliative care for self
      reported Japanese trimethylaminuria subjects.
AB  - Trimethylaminuria is caused by excessive malodorous trimethylamine excreted via
      urine and body secretion by decreased hepatic flavin-containing monooxygenase 3
      (FMO3) metabolic capacity for transforming non-odorous trimethylamine N-oxide.
      This study investigates foodstuff first in healthy volunteers for palliative care
      for self-reported Japanese trimethylaminuria subjects. Urinary excretion of total
      trimethylamine in volunteers was determined by gas chromatography under daily
      food intake or after ingestion of selected fish premeasured for total
      trimethylamine content. Frequency of individuals showing apparently <40% FMO3
      metabolic capacity was 3.8% in 365 Japanese volunteers who suffered from self
      reported malodor. Bonitos, especially red flesh, had the lowest total
      trimethylamine content (approximately 1 micromol per g tissue) among salmon,
      tuna, swordfish, sea bream or cod in this study. Mean excretion ratio of total
      trimethylamine in 8 h-urines from six healthy volunteers was approximately 90%
      after loading test by ingesting bonito (200 g) resulting in less than 2 micromol
      of free trimethylamine/mmol creatinine excreted in volunteers harboring high FMO3
      metabolic capacity, in contrast to approximately 40% after ingestion of 200 g
      cod. These results in healthy volunteers suggest that bonito may be one of the
      best nutrient sources and palliative care for self-reported Japanese
      trimethylaminuria subjects.

PMID- 20045991
TI  - Ethnic differences of two non-synonymous single nucleotide polymorphisms in CDA
      gene.
AB  - Cytidine deaminase, encoded by the CDA gene, catalyzes anti-cancer drugs
      gemcitabine and ara-C into their respective inactive metabolites. In CDA, two
      functionally significant non-synonymous polymorphisms, 79A>C (Lys27Gln) and
      208G>A (Ala70Thr), have been found and their minor allele frequencies (MAFs) were
      reported in Japanese and Chinese patients and a relatively small numbers of
      healthy volunteers in Caucasians and Africans. In this study, we determined the
      MAFs of both polymorphisms in 200 healthy volunteers of Koreans, along with 206
      Japanese, 200 Chinese-Americans, 150 Caucasian-Americans and 150 African
      Americans to reveal ethnic differences. MAFs of 79A>C (Lys27Gln) were 0.153 in
      Koreans and 0.327 in Caucasian-Americans, 0.204 in Japanese, 0.155 in Chinese
      Americans and 0.087 in African-Americans. MAFs of 208G>A (Ala70Thr) were 0.005 in
      Koreans and 0.022 in Japanese and the minor allele was not detected in Chinese
      Americans, Caucasian-Americans or African-Americans. Thus possibly, MAF of 208G>A
      in Japanese is likely to be somewhat higher than in Koreans and Chinese
      Americans. These data would provide fundamental and useful information for
      pharmacogenetic studies on cytidine deaminase-catalyzing drugs.

PMID- 20045992
TI  - Genetic variations in the HGPRT, ITPA, IMPDH1, IMPDH2, and GMPS genes in Japanese
      individuals.
AB  - Thiopurines (such as azathioprine and 6-mercaptopurine) are widely used for the
      treatment of patients suffering from malignancies, rheumatic disease,
      inflammatory bowel disease and solid organ transplant rejection. These drugs are
      activated and eliminated by a number of enzymes in the human body. This analyzes
      all the exons and exon-intron junctions of 5 enzyme genes (hypoxanthine-guanine
      phosphoribosyltransferase, HGPRT; inosine triphosphate pyrophosphatase, ITPA;
      inosine monophosphate dehydrogenases 1 and 2, IMPDH1 and IMPDH2 and guanosine
      monophosphate synthetase, GMPS) involved in the metabolism of thiopurine drugs.
      Twelve novel single nucleotide polymorphisms (SNPs) (HGPRT: IVS6-12C>A
      (frequency:0.003); ITPA: 569T>C (Phe189Phe, 0.003); IMPDH1: IVS8-15C>A (0.003),
      IVS9+227A>G (0.003), IVS17+115C>T (0.003), and 930C>T (Thr310Thr, 0.005); IMPDH2:
      IVS1+50G>T (0.003), IVS2+15G>A (0.010), IVS3-20G>A (0.003), 609C>T (Arg203Arg,
      0.003), and 1534C>T (Arg512Trp, 0.003); and GMPS: 1563T>C (Gly521Gly, 0.003)) and
      7 known SNPs (ITPA: 94C>A (Pro32Thr, 0.005), 138G>A (Gln46Gln, 0.586), and 563G>A
      (Glu187Glu, 0.433); IMPDH1: 987G>C (Leu329Leu, 0.113) and 1575A>G (Ala525Ala,
      0.620) and GMPS: IVS5-7T>C (0.153), 993A>G (Thr331Thr, 0.153)) were identified in
      200 Japanese subjects. These data should provide useful information for
      thiopurine therapy in the Japanese and as well as other Asian populations.

PMID- 20045993
TI  - Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and
      ATP7B in Japanese cancer patients.
AB  - ATP7A and ATP7B are involved in cellular resistance to platinum compounds such as
      cisplatin. By sequencing ATP7A, 38 genetic variations, including 30 novel ones
      were detected from 203 Japanese cancer patients. Of these, seven nonsynonymous
      variations were found: novel 1030A>G (R344G), 2111A>G (Q704R), 2200C>A (Q734K),
      2948C>T (T983M) and 3112G>A (V1038I) at 0.004 frequencies and known 2299G>C
      (V767L) and 4390A>G (I1464V) at 0.351 and 0.075 frequencies, respectively.
      Regarding ATP7B, 28 novel and 33 known genetic variations were detected including
      13 nonsynonymous ones: novel 1258A>G (M420V), 1426G>A (A476T), and 2401A>C
      (T801P) were found at 0.002, 0.005, and 0.002, respectively and known 1216G>T
      (A406S), 1366G>C (V456L), 2495A>G (K832R), 2785A>G (I929V), 2855G>A (R952K),
      2871delC (P957PfsX9), 3419T>C (V1140A), 3836A>G (D1279G), 3886G>A (D1296N) and
      3889G>A (V1297I) at 0.483, 0.463, 0.387, 0.005, 0.384, 0.005, 0.387, 0.002,
      0.012, and 0.015 frequencies, respectively. Linkage disequilibrium between
      detected variations was also analyzed. Our results would provide fundamental and
      useful information for genotyping ATP7A and ATP7B in the Japanese and probably
      other Asian populations.

PMID- 20045994
TI  - Five year study of cardiovascular risk factors in Japanese people: implications
      concerning new onset of metabolic syndrome.
AB  - BACKGROUND: The incidence of metabolic syndrome (MetS) has not been fully
      studied. METHODS AND RESULTS: The data of 35,534 subjects who underwent a health
      examination both in 1996 and 2001 were analyzed. Since the waist circumference
      was not available, modified criteria of MetS was used for those with 3 or more of
      the following items: 1) body mass index (BMI) >or=25 kg/m(2), 2) blood pressure
      >or=130 mm Hg in systolic and/or >or=85 mm Hg in diastolic, 3) triglycerides
      >or=150 mg/dL, 4) high-density lipoprotein (HDL) cholesterol <or=40 mg/dL in men,
      <or=50 mg/dL in women, and 5) fasting blood glucose (FBG) >or=100 mg/dL. The
      subjects who underwent therapy for hypertension, diabetes mellitus, and high TG
      were considered to have these items. The incidence of MetS over 5 years was
      determined and its risks were evaluated by Cox proportional-hazards models.
      During the follow-up of exactly 5 years, MetS developed in 2,853 (9.32%) among
      30,623 subjects who had no MetS at baseline. The subjects who developed MetS were
      older, and had elevated BMI, blood pressure, TG and FBG (p<0.001 for all) and
      lower HDL (p<0.034 for men and p<0.001 for women). Each item of MetS and their
      combination was associated with a higher risk to develop MetS. Obesity (BMI
      >or=25 kg/m(2)) alone or in combination with another item was associated with a
      higher risk to develop MetS suggesting it plays a key role. CONCLUSION: MetS
      using BMI developed in 9.32% over 5 years or 1.86%/year. Each item of MetS or
      their combination showed a high risk to develop MetS. Obesity was associated with
      a higher hazard ratio to develop MetS.

PMID- 20045995
TI  - Registry of 919 patients with thrombotic microangiopathies across Japan: database
      of Nara Medical University during 1998-2008.
AB  - BACKGROUND: Thrombotic microangiopathies (TMAs) are pathological conditions
      characterized by generalized microvascular occlusion by platelet thrombi,
      thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes
      of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic
      purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13: AC) is
      more specific for TTP, but not for HUS. Since 1998, our laboratory has functioned
      as a nationwide referral center for TMAs by analyzing ADAMTS13. METHODS: Of 1,564
      patients tested from 426 hospitals, 919 were positive for TMA. Levels of
      ADAMTS13: AC and the ADAMTS13 neutralizing autoantibody (ADAMTS13: INH) were
      determined by chromogenic act-ELISA and/or by classic von Willebrand factor
      multimer assay. RESULTS: TMA patients consisted of two groups: severe (less than
      3% of normal control) and non-severe deficiency of ADAMTS13: AC. Both groups were
      divided into congenital (n=65) and acquired (n=854) TMA. Of the former, 41 had
      congenital deficiency of ADAMTS13: AC, while the remaining 24 had disease of
      unknown etiology. The 854 patients with acquired TMA could be largely grouped
      into three categories: idiopathic TTP (n=284), idiopathic HUS (n=106), and
      secondary TMAs (n=464). The secondary TMAs were observed in heterogeneous patient
      groups and were associated with drugs, connective tissue diseases, malignancies,
      transplantation, pregnancy, E. coli O157: H7 infection, and other factors. All of
      the patients with acquired severe ADAMTS13: AC deficiency were positive for
      ADAMTS13: INH. CONCLUSION: Although TMAs are highly heterogeneous pathological
      conditions, one-third of TMA patients have severe deficiency of ADAMTS13: AC.
      Platelet transfusions to such patients are contraindicated. Rapid ADAMTS13: AC
      assays are therefore prerequisite to appropriately treat TMA patients.

PMID- 20045996
TI  - Insomnia and depression during protective isolation in patients with
      hematological disorders.
AB  - OBJECTIVE: Patients treated in a protective isolation unit (PIU) often experience
      loneliness and increased feelings of seclusion, leading to elevated levels of
      distress, but the relationship between psychiatric distress and environmental
      factors is unclear. Therefore, we retrospectively compared the impact of
      environmental factors on insomnia and depression between patients in the PIU and
      those in a standard ward (SW). METHODS: Subjects were 246 patients with
      hematological disorders hospitalized in Meitetsu Hospital between April 1, 2007
      and July 31, 2008 (62 PIU patients and 184 SW patients). We assessed insomnia and
      depression, as well as concomitant corticosteroid (CS) administration, stem cell
      transplantation (SCT) therapy, and complications resulting from these therapies.
      Details of medical history and patient information were retrospectively extracted
      from patients' charts, medical records and the electronic laboratory database at
      the hospital. RESULTS: Patients in the PIU tended to be complicated by insomnia
      or depression more than those in the SW, but the stay in the PIU was not
      significantly related to the incidence of insomnia or depression. Our findings
      indicated that use of CS was a risk factor for insomnia. The prevalence of
      depression was higher in patients with therapeutic complications. All PIU
      patients with depression also received SCT. CONCLUSION: Our findings suggest an
      increased potential for insomnia after administration of CS and depression in
      cases with complications after SCT, which is important to keep in mind for
      patients with hematological disorders.

PMID- 20045997
TI  - Evaluation of respiratory impedance in asthma and COPD by an impulse oscillation
      system.
AB  - OBJECTIVE: The purpose of this study was to clarify the differences in
      physiological properties of the airways between asthma and COPD using an impulse
      oscillation system (IOS). PATIENTS AND METHODS: Subjects comprised 95 stable COPD
      patients, 52 never-smoker asthma patients and 29 healthy never-smokers >60 years
      old, all matched for age, in whom respiratory impedance was examined by IOS.
      RESULTS: In both asthma and COPD patients, a significant increase in respiratory
      resistance (Rrs5) and more negative value of respiratory reactance (Xrs5) at 5 Hz
      of oscillatory frequency with an increase in resonant frequency (fres) were
      observed when compared with healthy never-smokers. In asthma, a significant
      increase in respiratory resistance at 20 Hz (Rrs20) was also observed when
      compared with healthy never-smokers and COPD. The increases in Rrs5 and relative
      changes of Xrs5 to more negative were remarkable with increasing severity of
      COPD. On the other hand, among patients with asthma, these changes in Rrs5 and
      Xrs5 were also observed in asthmatics with normal FEV(1)/FVC. Interestingly, Xrs5
      showed further changes to more negative in expiration of tidal breath in severe
      COPD, whereas no significant changes in Xrs5 to more negative in expiration was
      observed in healthy never-smokers and asthmatics with and without normal
      FEV(1)/FVC. CONCLUSION: IOS may be useful for detecting pathophysiological
      changes of respiratory system in accordance with severity of COPD and even in
      asthmatics with normal FEV(1)/FVC. The larger within-breath changes of Xrs5 to
      more negative in severe COPD may represent easy collapsibility of small airways
      in expiration of tidal breath. These properties may help to analyze airway
      mechanics and to identify abnormalities of the airways that cannot be found by
      spirometry alone.

PMID- 20045998
TI  - Analysis of an outbreak of Salmonella enteritidis by repetitive-sequence-based
      PCR and pulsed-field gel electrophoresis.
AB  - OBJECTIVE: The aim of this study was to investigate a large food-borne outbreak
      associated with eggs contaminated by Salmonella Enteritidis in a military unit
      using pulse field gel electrophoresis (PFGE) and the Repetitive-sequence-based
      PCR (rep-PCR) employing the DiversiLab system. MATERIALS AND METHODS: In mid
      January 2008, a food-borne outbreak associated with S. Enteritidis occurred in a
      military unit located in the city centre of Isparta. A total of 2,469 patients
      were registered to six hospitals with gastrointestinal disease symptoms such as
      diarrhea and abdominal pain. Of those registered, 445 were hospitalized. S.
      Enteritidis was isolated from 276 stool samples and a blood sample of the
      hospitalized patients and from a food item. The PFGE patterns after XbaI
      digestion and rep-PCR profiles produced by the DiversiLab system were determined
      for eight randomly selected stool isolates, one blood isolate and one food
      isolate. RESULTS: The PFGE patterns of all isolates were identical. The Rep-PCR
      profiles produced by using the DiversiLab system showed that all isolates were
      indistinguishable. The PFGE and rep-PCR interpretations were concordant for the
      S. Enteritidis isolates. All stool isolates, one blood isolate and one food
      isolate were susceptible to all antibiotics tested. CONCLUSION: This data suggest
      that the DiversiLab system may be a reasonable alternative to PFGE for
      investigation and control of S. Enteritidis outbreaks, since it is easy to use,
      rapid and does not require highly skilled operators.

PMID- 20045999
TI  - IgA nephropathy in two patients with Sjogren's syndrome: one with concomitant
      autoimmune hepatitis.
AB  - Concurrent glomeruli and liver involvement in patients with Sjogren's syndrome
      (SS) has seldom been reported. Meanwhile, IgA nephropathy (IgAN) associated with
      SS is not as common as other types of glomerulonephritis, such as
      membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN).
      Two patients with SS and IgAN are presented. Case 1 was diagnosed as SS
      complicated with IgAN (Haas subclass III) and severe AIH, while case 2 was
      diagnosed as SS and IgAN (Haas subclass I) with serious tubulointerstitial
      lesions. The true prevalence of IgAN secondary to SS is certainly underestimated
      and the crucial pathogenetic factors may be polyclonal hypergammaglobulinemia and
      hypocomplementemia (especially C4). The frequent presence of multiple
      immunoglobulin and complement deposition in glomeruli, especially weak deposits
      of C4 and (or) C1q, is an immunofluorescence staining feature of IgAN secondary
      to SS and may be associated with disease severity and activity.

PMID- 20046000
TI  - A frame-shift mutation in the SLC34A2 gene in three patients with pulmonary
      alveolar microlithiasis in an inbred family.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by the
      presence of small calculi in the alveolar space. The SLC34A2 is thought to be
      responsible for the disease. We encountered three siblings of an inbred family
      who have PAM. We examined the family of the proband who was admitted with dyspnea
      on exertion and cough, and eventually was diagnosed with PAM. Genetic analysis
      revealed that both parents (a consanguineous marriage) of the proband were
      carriers with heterozygous mutation of SLC34A2 gene, and three of their children
      were diagnosed with PAM with homozygous mutation in the SLC34A2 gene. These
      findings suggest that impaired activity of the SLC34A2 gene may be responsible
      for familial PAM.

PMID- 20046001
TI  - Intravascular large B-cell lymphoma presenting pulmonary arterial hypertension as
      an initial manifestation.
AB  - We report a 39-year-old man with intravascular large B-cell lymphoma (IVLBCL) who
      had been treated as a case with pulmonary arterial hypertension (PAH) for one
      year. After he became worse, diffuse pulmonary (18)F-fluorodeoxyglucose (FDG)
      uptake in positron emission tomography (PET) suggested the existence of IVLBCL in
      the lung showing normal CT images. The diagnosis was confirmed with random
      transbronchial lung biopsy, and he was then successfully treated. Since IVLBCL
      presenting PAH has been rare and is difficult to diagnose, early application of
      FDG-PET may provide early recognition of the disorder, leading to a better
      outcome.

PMID- 20046002
TI  - Regression of giant bullous emphysema.
AB  - Spontaneous resolution of bulla associated with infection or tumor is
      occasionally observed. However, resolution of progressively enlarging giant
      bullous emphysema (GBE) after medical therapy has not been reported. A 51-year
      old man smoker with GBE on the right lung was referred to Samsung Medical Center
      for the consideration of bullectomy. A review of his medical records revealed
      that right-side bullous emphysema had been detected 4 years previously and it had
      progressively enlarged with a concomitant deterioration of lung function.
      Although he had a history of chronic asthma, he had never been treated on a
      regular basis. After combination therapy, including regular tiopropium, a
      salmeterol/flucatisone inhaler, a salbutamol inhaler as needed, and oral
      theophylline therapy, right side bulla showed marked regression. This regression
      of bulla was associated with an improved forced expiratory volume in one second
      and normalization of residual volume. This case serves as a reminder to
      clinicians that medical treatment for underlying diseases should precede surgical
      consideration in patients with GBE.

PMID- 20046003
TI  - Polymyxin B-immobilized fiber column hemoperfusion treatment for drug-induced
      severe respiratory failure: report of three cases.
AB  - The effects of direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP)
      treatment for acute exacerbation of interstitial pneumonia have been reported.
      Here, we report 3 severe cases of drug-induced interstitial lung disease (DI-ILD)
      that were treated with PMX-DHP. Two DI-ILD cases were caused by methotrexate, and
      the third case was caused by the herbal medicine sanmotsu-ogon-to. The arterial
      oxygen tension/inspiratory oxygen fraction ratio improved during PMX-DHP
      treatment in all 3 patients. Finally, 2 patients survived and 1 died. The study
      findings indicate that PMX-DHP treatment is a viable option for the management of
      acute respiratory failure in patients with DI-ILD.

PMID- 20046004
TI  - Signal change of the substantia nigra on diffusion-weighted imaging following
      striatal infarction.
AB  - Diffusion-weighted imaging can depict secondary signal changes of the substantia
      nigra in patients with ipsilateral striatal infarction. We report four patients
      who demonstrated obvious signal changes of the substantia nigra in the subacute
      phase of stroke. Embolic stroke was diagnosed in all of the cases, and none of
      the patients presented clinical deterioration in their course. Embolic mechanism
      might be more closely related to the secondary change of the substantia nigra
      than thrombosis. The relationship between secondary nigral degeneration and
      stroke etiology or between the nigral lesions and recanalization of the middle
      cerebral artery remains unclear.

PMID- 20046005
TI  - Pseudo-internuclear ophthalmoplegia as a sign of overlapping myasthenia gravis in
      a patient with 'intractable' hypothyroidism.
AB  - We describe a 52-year-old man with a history of increasing fatigability and gait
      disturbances that were first attributed to hypothyroidism. On examination, he had
      bilateral pseudo-internuclear ophthalmoplegia with weakness of adduction and
      abducting nystagmus. Convergence was also impaired and he showed proximal
      weakness of the limb. Intravenous edrophonium almost completely abolished the
      nystagmus and adducting muscle weakness, and improved the strength of proximal
      muscles groups. The clinical response to the administration of edrophonium, the
      presence of AChR binding antibodes and the repetitive nerve stimulation test
      findings indicated that the patient had pseudo-internuclear ophthalmoplegia as a
      manifestation of generalized myasthenia gravis. Whereas hypothyroidism was
      effectively controlled with levothyroxine, his subsequent response to thymectomy,
      prednisolone and cholinesterase inhibitors confirmed the diagnosis of generalized
      myasthenia gravis.

PMID- 20046006
TI  - Anti-neuronal antibodies in acute pandysautonomia.
AB  - We encountered two patients with acute pandysautonomia who subacutely exhibited
      extensive autonomic dysfunction after antecedent infections. Although these
      patients had been suffering from autonomic disturbance for several months, they
      both had a good clinical course after plasma exchange and intravenous
      immunoglobulin therapy. Thin-layer chromatography (TLC)-immunostaining did not
      demonstrate any antibodies against gangliosides, but immunoblot analysis showed
      antibodies against a neuroblastoma cell line, SH-SY5Y, in serum samples.
      Furthermore, ganglionic acetylcholine receptor autoantibodies were detected in
      one patient. These findings suggest that neuronal antibodies against the
      autonomic nervous system play an important role in the pathogenesis of acute
      pandysautonomia.

PMID- 20046007
TI  - Parvovirus B19 infection and acute myocarditis.

PMID- 20046008
TI  - Cardiac magnetic resonance imaging helps make the diagnosis of left ventricular
      diverticulum in an adult patient with total occlusion of the coronary artery.

PMID- 20046009
TI  - Echocardiographic diagnosis of aortic intramural hematoma via the posterior
      paraspinal window.

PMID- 20046010
TI  - A young woman with Maffucci syndrome.

PMID- 20046011
TI  - A patient with acro-osteolysis syndrome: Hajdu-Cheney.

PMID- 20046012
TI  - [Early diagnosis of connective tissue disease-related pulmonary hypertension].
AB  - It is known that prognosis of pulmonary hypertension (PH), especially connective
      tissue disease related PH (CTD-PH), is serious. CTD-PH is caused by not only
      pulmonary arterial hypertension, but also interstitial pneumonitis, hypoxia,
      chronic thromboembolism of pulmonary artery, or left heart diseases. Recently,
      prognosis of PH is improved by progress of diagnostic measures including
      echocardiography and development of effective vasodilators. However, early
      diagnosis of PH is necessary for further improvement of the prognosis. Previous
      reports have shown that diffusion lung capacity for carbon monoxide (DLco) is
      reduced in the early phase of PH, and we have shown that serum lactate
      dehydrogenase level is also elevated in this phase. Furthermore, we have been
      studying significance of stress echocardiography. Therefore, if reduced DLco or
      LDH elevation are recognized, follow up of laboratory data such as blood levels
      of KL-6, NT-proBNP, D-dimer, echocardiography, high resolution CT of the lung, in
      addition to clinical findings are important for prediction of PH.

PMID- 20046013
TI  - [Role of T-cell leukemia translocation-associated gene (TCTA) protein in human
      osteoclastogenesis].
AB  - Synovial tissues of patients with rheumatoid arthritis (RA) include factors
      regulating bone resorption, such as receptor activator NF-kappaB ligand (RANKL),
      TNF-alpha, IL-6, IL-17, and IFN-gamma. However, in addition to these cytokines,
      other factors expressed in synovial tissues may play a role in regulating bone
      resorption. In 2009, we demonstrated that novel peptides from T-cell leukemia
      translocation-associated gene (TCTA) protein expressed in synovial tissues from
      patients with RA inhibit human osteoclastogenesis, preventing cellular fusion via
      the interaction between TCTA protein and a putative counterpart molecule. Only a
      few studies on the role of TCTA protein have been reported, including our report
      published in 2009. In the current review paper, we summarized papers on TCTA
      protein before 2009 and our recent findings.

PMID- 20046014
TI  - [Novel animal models for bullous pemphigoid utilized by "humanization of
      autoantigen"].
AB  - Animal models of human diseases are very useful to better understand their
      pathomechanism and to develop new therapies. However, due to the differences
      among different species, it is sometimes difficult to reproduce reliable diseases
      phenotype in animals. Bullous pemphigoid is the most common autoimmune blistering
      skin disease, in which circulating IgG autoantibodies directed against type XVII
      collagen (COL17) leads to skin blister formation. Interestingly, due to
      significant interspecies differences in its amino acid sequences in major
      pathogenic epitope on COL17, passive transfer of auto-antibodies (Abs) from
      patients with bullous pemphigoid into mice failed to induce blister formation. To
      overcome this species' differences, we have recently established a novel
      molecular method "humanization of autoantigen" by genetic manipulation. Using
      COL17-humanized mice, we have established 2 different mouse models of bullous
      pemphigoid. One is by injecting human auto-Abs from bullous pemphigoid patients
      into the neonatal COL17-humanized mice. Another model was induced by mouse Abs to
      human COL17 passively transferred from mother via placenta and milk into the
      neonatal COL17-humanized mice. "Humanization of autoantigen" is a novel and
      potential method to produce animal models for autoimmune diseases.

PMID- 20046015
TI  - [IgG4-related disease-the diagnostic confusion and how to avoid it].
AB  - Since Hamano et al. have first reported serum IgG4 elevation in sclerosing
      pancreatitis in 2001, various systemic disorders have been reported to be related
      to elavated IgG4, and many names have been proposed from the point of view of the
      systemic condition. Despite similarities in the organs damaged in IgG4-related
      Mikulicz's disease and Sjogren's syndrome, there are marked clinical and
      pathological differences between the two entities. IgG4-related Mikulicz's
      disease and Kuttner's tumor are related diseases and complete differentiation is
      very difficult. The majority of cases diagnosed with autoimmune pancreatitis in
      Japan are IgG4-related sclerosing pancreatitis, and it should be recognized that
      this is distinct from the western type. There is a likelihood that cases once
      diagnose as Castleman's disease that showed good responsiveness to glucocorticoid
      treatment may have been IgG4-related lymphadenopathy, and should be re-assessed
      in light of recent findings. Diagnosis of IgG4-related disease is defined by both
      1) Elevated serum IgG4 (>135 mg/dl) and 2) Histopathological features including
      lymphocyte and IgG4(+) plasma cell infiltration (IgG4(+) plasma cells/IgG(+)
      plasma cells >50% on a highly-magnified slide checked in five points), however
      differential diagnosis from other distinct disorders, such as sarcoidosis,
      Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other
      existing conditions is necessary. To avoid diagnostic confusion, simpler and more
      scientific names should be used where disease-specific pathogenesis or markers
      have been ascertained.

PMID- 20046016
TI  - [Is rheumatoid arthritis without anti-citrullinated peptide antibody a
      genetically distinct subset?].
AB  - These days, rheumatoid arthritis (RA) is reported to be subclassified into two
      subsets by anti-citrullinated peptide antibody (ACPA) positivity. Clinically,
      ACPA positive RA tends to develop more severe arthritis than ACPA negative RA. In
      addition, a lot of reported susceptibility genes to RA (ie. HLA-DRB1(*)04,
      PTPN22, TRAF1/C5, CTLA4) are found to be associated only with ACPA positive RA
      but not with ACPA negative RA. It is getting clear that HLA-DRB1(*)04, which was
      believed to be primarily associated with RA, is not a primary risk factor but
      ACPA is. Then, a hypothesis for the disease mechanism of ACPA positive RA is set
      as follows; citrullination possibly due to smoking, etc, provokes ACPA production
      in individuals who have susceptibility alleles of genes including HLA, followed
      by joint inflammation in autoantibody-dependent manner. The search for
      susceptibility genes for ACPA negative RA is slowly progressing, but only a few
      genes are so far reported: HLA-DRB1(*)03 for Caucasian, HLA-DRB1(*)09 for
      Japanese, IRF5 and STAT4. When we investigate the disease mechanisms of RA, we
      should manage independently the two disease subsets : ACPA positive and ACPA
      negative RA.

PMID- 20046017
TI  - [Case of systemic lupus erythematosus repeated with various allergic reactions by
      trimethoprim-sulfamethoxazole].
AB  - A 23-year-old Japanese woman was diagnosed with lupus nephritis on May 2007. The
      patient was prescribed 30 mg/day of prednisolone, but developed a pulmonary
      abscess and was admitted to Sapporo Medical University Hospital in March 2008.
      Antibiotics improved the symptoms. We prescribed trimethoprim-sulfamethoxazole as
      prophylaxis for pneumocystis pneumonia; however, the patient developed fever and
      thrombocytopenia with hyperferritinemia after a week of this prophylaxis. We
      considered that she was developing hemophagocytic syndrome, and administered
      methylprednisolone pulse therapy. The clinical findings soon improved. However,
      when the prophylaxis was restarted, the patient developed fever, headache, and
      anaphylaxis the same day. Symptomatic therapy resolved these symptoms after three
      days, but they recurred on recommencing trimethoprim-sulfamethoxazole. Analysis
      of the cerebrospinal fluid revealed aseptic meningitis. These episodes were
      thought to be induced by trimethoprim-sulfamethoxazole. As trimethoprim
      sulfamethoxazole is frequently used as prophylaxis for pneumocystis infection in
      immunosuppressed patients, clinicians should be vigilant regarding the
      complications of this treatment, particularly the rare occurrence of aseptic
      meningitis and anaphylaxis.

PMID- 20046018
TI  - [Investigation of the clinical usefullness of leukocytapheresis on rheumatoid
      arthritis resistant to or failed with the other treatments].
AB  - PURPOSE: To examine therapeutic effect of leukocytapheresis (LCAP) for rheumatoid
      arthritis (RA) resistant to various treatments. METHOD: Thirteen patients with RA
      (mean age : 60.8+/-11.4, male : female=5 : 8), 1 who were resistant to disease
      modifying anti-rheumatic drugs (DMARDs) and biologics, or 2 who failed with those
      medicines because of side effects or complications. We performed LCAP, which was
      carried out once a week for a total of five sessions, with a throughput of about
      0.1 L/kg. Before and after LCAP, we evaluated the effect of LCAP therapy. RESULT:
      DAS28 (CRP) score was 5.70+/-1.12 before LCAP, 4.57+/-1.19 (P<0.05) just after
      the final LCAP and 4.83+/-1.35 (P<0.05) about 4 weeks after LCAP. DAS28 score
      decreased in all patients after LCAP. No serious adverse events were observed
      except temporary anemia. CONCLUSION: LCAP therapy may be useful and safe for
      patients with RA resistant to conventional medication. Patients who show good
      clinical response by LCAP needs to be clarified.

PMID- 20046019
TI  - [Microscopic polyangiitis in a patient on hemodialysis : a case report].
AB  - A 62-year-old male was admitted to a local hospital due to a clouding of
      consciousness in October 2006. On admission, his renal function was observed to
      have severely deteriorated, which is thought to cause disturbance of
      consciousness. Laboratory data showed blood urea nitrogen to be 160 mg/dl and the
      serum creatinine level was 25 mg/dl and, as a result, continuous
      hemodiafiltration (CHDF) was started. Although his general condition improved,
      his renal function did not recover. Therefore, regular hemodialysis was started
      in December 2006. The cause of renal dysfunction was uncertain, because MPO-ANCA
      was negative, and a renal biopsy could not be done due to the lack of a clear
      corticomedullary border in his kidneys. In January 2008, he was diagnosed to have
      microscopic polyangiitis (MPA) because of hemoptysis, elevated serum CRP levels
      and a positive finding for MPO-ANCA (408.0 EU). An alveolar hemorrhage was also
      ascertained in a broncoscopic examination. Steroid pulse therapy and intravenous
      pulse therapy of cyclophosphamide were thus started. The patient's clinical
      symptoms thereafter significantly improved and his MPO-ANCA level became
      normalized. This is a rare case characterized by a late appearance of MPO-ANCA,
      which occurred after more than one year after the onset of renal failure in MPA.

PMID- 20046020
TI  - Case of Chlamydia-associated arthritis.
AB  - We report a case of Chlamydia-associated arthritis in a 40-year-old man. The
      patient experienced four episodes of Chlamydia trachomatis urtethritis within a
      few years. During the present episode, polyarthritis developed a few days after
      Chlamydia trachomatis urethritis was noted. The patient was diagnosed as having
      Chlamydia-associated arthritis. Loxoprofen sodium and azithromycin were started.
      Antibiotics induced clinical improvement of urethritis, although arthritis
      persisted for 3 months. HLA-B27 was negative, but both HLA-B35 and B40 were
      positive. Thus, we speculate that positivity for both HLA-B35 and HLA-B40
      contributed to the persistence of arthritis in this case. During the course, the
      levels of Th1, Th17 and regulatory T cells in the peripheral blood were increased
      on flowcytometry. Thus, we speculate that Th17 may play, at least in part, an
      important role of the pathogenesis in this case.

PMID- 20046021
TI  - Pathomechanism of cellular infiltration in the perivascular region of several
      organs in SAMP1/Yit mouse.
AB  - We investigated the histological changes of extra-intestinal organs, such as the
      liver, kidney, lung and pancreas in SAMP1/Yit mice, a human Crohn's disease
      model, using immunohistochemical techniques. The perivascular cellular
      infiltration was detected around the small vessels after 30 weeks. These
      infiltrating cells consisted of many CD4-positive T-lymphocytes, and small
      numbers of CD8- positive T-lymphocytes and IgG-positive B-lymphocytes. MAdCAM-1
      and VCAM-1 were detected in vascular endothelial cells in non-affected regions of
      13 and 20 week-old, as well as in the affected regions showing perivascular
      cellular infiltration after 30 weeks. In addition, integrin alpha4beta7 was
      detected on these infiltrating cells in the perivascular regions after 30 week
      old. LT-beta and IL-12, cytokines of the Th-1-type immune response, were not
      observed in these affected regions. However, IL-4, one of the cytokines of the Th
      2-type immune response, was detected on the perivascular infiltrating cells after
      30 week-old. These results revealed that the changes in extra-intestinal organs
      were mainly caused by infiltration of CD4-positive T-lymphocytes into the
      perivascular regions in SAMP1/Yit mice. These cellular infiltrations were thought
      to be initiated by adhesion of CD4-positive T-lymphocytes to the endothelial
      cells mediated by MAdCAM-1 and integrin beta7. Immunohistochemistry for Th
      related cytokines indicated that the perivascular cellular infiltration was
      developed by the Th-2-type immune response in the extra-intestinal organs of
      SAMP1/Yit mouse.

PMID- 20046022
TI  - Crossreactivity of antibodies to canine CD25 and Foxp3 and identification of
      canine CD4+CD25 +Foxp3+ cells in canine peripheral blood.
AB  - The importance of CD4(+)CD25(+)Foxp3 (+) regulatory T cells (Treg cells) in
      immune response is increasingly being recognized. However, to date, only a few
      studies on these cells have been conducted in canine species, partly because of
      the unavailability of appropriate antibodies to detect this cell population. In
      this study, the crossreactivities of anti-human CD25 antibody (clone ACT-1) and
      anti-mouse Foxp3 antibody (clone FJK16s) to canine CD25 and Foxp3, respectively,
      were confirmed using cell lines overexpressing either of these genes. By using
      these antibodies, we determined if CD4(+), CD25(+), or Foxp3(+) cells were
      present in unstimulated canine peripheral blood mononuclear cells (PBMCs) and in
      concanavalin A (ConA)-stimulated PBMCs. CD25(+) cells were not detected in
      unstimulated canine PBMCs, unlike in human or mouse PBMCs. ConA stimulation of
      canine PBMCs induced Foxp3 and CD25 expression in CD4(+) and CD4(-) cells. These
      data indicate that the activation of canine lymphocytes might induce the
      production of adaptive Treg cells, as observed in humans.

PMID- 20046023
TI  - Epidemiological study of hantavirus infection in the Samara Region of European
      Russia.
AB  - European Russia is a highly endemic area of hemorrhagic fever with renal syndrome
      (HFRS), a rodent-borne zoonotic disease, caused by hantaviruses. In total, 145
      small mammals of four species (Myodes glareolus, Apodemus flavicollis, A.
      agrarius, and A. uralensis) were trapped in the Samara region of European Russia
      in August 2005 and examined for the presence of hantavirus (HV). Anti-HV
      antibodies were found in six of 68 (8.8%) M. glareolus and in one of 19 (5.3%) A.
      flavicollis by indirect immunofluorescent antibody assay (IFA). The Puumala virus
      (PUUV), which is one of the hantavirus species, was detected in the lungs of
      seven M. glareolus by RT-PCR. The virus S-segment was extremely similar (96.2% to
      99.3%) to the sequence found in a fatal case of HFRS in the Samara region.
      Phylogenetic analyses of S and M segments showed that the Samara PUUVs form a
      cluster within the Russian Volga lineage and apparently differ from other
      European PUUVs. Anti-PUUV antibodies were found in blood sera from seven HFRS
      patients and from one undiagnosed patient from the Samara region, using IFA and
      an enzyme-linked immunosorbent assay (ELISA). These data suggest that the bank
      vole M. glareolus is a primary natural reservoir and vector for PUUV, which is
      the main causative agent of HFRS in humans in the Samara region.

PMID- 20046024
TI  - A high percentage of pigs born dead in litters in high-, intermediate- and low
      performing herds.
AB  - The objectives of the present study were to measure a percentage of pigs born
      dead in the number of total pigs born (PPBD), and to investigate an association
      between PPBD and total pigs born by parity groups and three herd groups formed on
      the basis of the pigs weaned per mated female per 6 years (PWMFY). The studied
      data included 236,805 parity records of 51,443 sows in 110 herds. The three herd
      groups, high-, intermediate- and low-performing herds, were formed on the basis
      of the upper and lower 25th percentiles of PWMFY. Linear mixed-effects models
      were performed to analyze the data. Mean (+/- SEM) PPBD was 9.6 (+/- 0.03) %.
      Sows in high-performing herds had lower PPBD for all parity groups than those in
      low-performing herds (P<0.05). Parity 2 sows had the lowest PPBD between parity
      groups (P<0.05). The PPBD increased from 7.0 to 13.2% as the parity number
      increased from 2 to >or= 6. Parity 1 sows had higher PPBD than parity 2 and 3
      sows (P<0.05). As the total pigs born increased from 10 to 16 pigs, PPBD
      increased in all the parity groups (P<0.05). In parity 3 or higher, PPBD in low
      performing herds increased more steeply than that in high-performing herds as
      total pigs born increased form 6 to 10 pigs. We suggest that farrowing management
      including assisted farrowing improve PPBD for sows in parity 3 or higher.

PMID- 20046025
TI  - Multivalent DNA vaccine enhanced protection efficacy against infectious
      bronchitis virus in chickens.
AB  - For efficacious DNA vaccine development against infectious bronchitis virus
      (IBV), the immunogenicity of a multivalent DNA vaccine was evaluated. Three
      expression plasmids each targeting spike protein (S1), nucleocapsid protein (N),
      and membrane protein (M) of IBV were prepared. Chickens were immunized with
      either individual plasmids (monovalent) or with a combination of all plasmids
      (multivalent). Immunization with the multivalent DNA vaccine induced synergistic
      augmentation of humoral and cellular responses in comparison with the individual
      vaccines, and provided up to 85% immune protection. Thus the multivalent DNA
      vaccine represents an innovative approach for enhancing DNA vaccine potency, and
      has potential clinical application for vaccination against IBV.

PMID- 20046026
TI  - 17Beta-estradiol induces gastrointestinal motility disorder by decreasing CPI-17
      phosphorylation via changes in rho-family G-protein Rnd expression in small
      intestine.
AB  - In the present study, we investigated the long-term effects of 17beta-estradiol
      on the motility of small intestine in in vitro organ culture and in vivo
      treatment studies. When rat ileal circular smooth muscle tissues were cultured
      with 17beta-estradiol (0.1 and 1 microM) for 5 days, carbachol-induced
      contraction was inhibited. In ileal tissue isolated from ovariectomized rat
      treated with 17beta-estradiol (200 microg/kg/day s.c. for 3 days), carbachol
      induced contraction was also impaired. Both in vitro and in vivo, 17beta
      estradiol treatment upregulated heat shock protein 27 (HSP27) expression,
      indicating the activation of estrogen receptor in the intestinal smooth muscle.
      17beta-estradiol did not change protein expression levels of RhoA and RhoA
      associated coiled coil-forming serine/threonine kinases (ROCKs); however, it
      upregulated Rnd2 and Rnd3, Rho-family G-proteins that counteract the functions of
      RhoA, both in vitro and in vivo. In organ culture, treatment of ileal tissue with
      17beta-estradiol greatly suppressed the carbachol-induced increase in
      phosphorylation at Thr38 in CPI-17 without altering total CPI-17 protein
      expression. These results suggest that 17beta-estradiol upregulates Rnd
      expression to inhibit the RhoA-mediated Ca(2+) sensitization of contractile
      mechanisms, which are mediated by CPI-17 phosphorylation in ileal smooth muscle.
      This mechanism may contribute to the intestinal motility disorder occurring in
      gender-dependent bowel diseases.

PMID- 20046027
TI  - Effects of fetal exposure to diethylstilbestrol on mammary tumorigenesis in rats.
AB  - The aim of this study was to investigate the effect of fetal exposure to
      diethylstilbestrol (DES) on the induction of mammary tumors induced by 7,12
      dimethylbenz[a]anthracene (DMBA) in female rats. Pregnant rats were fed only
      normal diet, diet mixed with 0.1 ppm DES throughout pregnancy period or diet
      mixed with 0.1, 1 or 10 ppm DES from day 13 of pregnancy till the end of
      pregnancy. Delivered pups were given 10 mg DMBA by gastric intubation at 50 days
      after birth and observed till 336 days after birth. Some rats exposed to DES
      throughout pregnancy and those from day 13 till the end of pregnancy showed
      endocrine disrupting effects such as absence of CL and active lactation in
      mammary glands at necropsy, while no abnormal estrus cycle such as persistent
      estrus was seen during the observation period until 88 days after birth. Fetal
      exposure to 0.1 ppm DES throughout pregnancy period, 0.1 and 1 ppm DES from day
      13 of pregnancy increased the incidence and number of mammary carcinomas (MCs) at
      the earlier period while exposure to 0.1 ppm DES throughout pregnancy period
      enhanced the incidence and number of benign proliferative lesions (PLs) at the
      later period. MCs appeared earlier than benign PLs. These results suggest that
      exposure to DES throughout pregnancy and from day 13 of pregnancy could induce
      endocrine disrupting conditions and enhance the induction of MCs and that
      exposure to DES throughout pregnancy enhance PLs.

PMID- 20046028
TI  - Proinflammatory cytokines suppress the expression level of protease-activated
      receptor-2 through the induction of iNOS in rat colon.
AB  - Protease-activated receptor (PAR)-2 plays important roles in intestinal
      inflammatory responses and also contributes to intestinal digestive motility. In
      the distal colon of a rat experimental colitis model, expression level of PAR-2
      mRNA was decreased, and relaxation through PAR-2 activation was attenuated. This
      study shows the effects of proinflammatory cytokines on changes to PAR-2 in rat
      colonic smooth muscle using an organ culture method. Colonic inflammation was
      induced in rats by administering dextran sodium sulphate in drinking water. Organ
      culture of distal colonic smooth muscle layer of normal rat was performed for up
      to 3 days. In the experimental colitis rat, mRNA expression levels of
      proinflammatory cytokines such as IL-1beta and TNF-alpha increased with
      inflammation. After the incubation with IL-1beta and TNF-alpha for 3 days,
      trypsin (PAR-2 agonist)-induced relaxation was attenuated, simultaneous with
      suppression of PAR-2 mRNA expression. Conversely, in this preparation, mRNA
      expression levels of iNOS were significantly increased. When l-NMMA was added to
      the medium with IL-1beta and TNF-alpha, changes to PAR-2 by these cytokine
      recovered. Moreover, when samples were cultured with NOC-18 (slow-releasing NO
      donor) for 3 days, relaxation induced by trypsin and expression of PAR-2 mRNA
      were attenuated. These results suggest that suppression of PAR-2 expression under
      inflammatory conditions is at least partially induced by NO produced in the
      colonic muscularis externa by proinflammatory cytokines.

PMID- 20046029
TI  - The feeding behavior of dogs correlates with their responses to commands.
AB  - Motivation is one of the most important factors in dog training. To generate
      motivation, people use various reinforcer mechanisms. In particular, many pet
      owners use food because it is simple and convenient. The aim of this study was to
      investigate the association between dogs' level of interest in food and their
      responsiveness to commands. Thirty-four dogs were divided into three groups based
      on their feeding patterns (Fast, Slow, and Leftover). The fast group (n=15) had
      the highest interest in food and showed a high response to commands when food was
      used as a reinforcer, rather than praise/stroking. The leftover group (n=6)
      showed the least interest in food and had a low reaction to commands, regardless
      of the reinforcer. In contrast, the slow group (n=13) had modest interest in food
      and maintained the same response to commands regardless of the reinforcer.
      Results of this study indicate that dogs' feeding patterns are indicative of
      their level of interest in food, and may be useful in determining the optimal
      training reinforcer. This can help dog owners improve their relationships with
      their dogs.

PMID- 20046030
TI  - Temporal changes in concentrations of branched-chain amino acids in plasma on
      healthy mares and foals from birth to 24 weeks of age.
AB  - The concentrations of branched-chain amino acids (BCAA; valine, leucine,
      isoleucine) were determined in plasma of 7 healthy thoroughbred mares and their
      foals from birth (0 week) to 24 weeks of age, using automated high-performance
      liquid chromatography. In foals, the concentrations of plasma valine were
      significantly high (p<0.05) at 16, 20 and 24 weeks. The concentrations of plasma
      leucine were significantly high (p<0.05) at 1 and 3 weeks. The concentrations of
      plasma isoleucine were significantly high (p<0.05) from 1 to 24 weeks. In mares,
      the concentrations of plasma valine were significantly high (p<0.05) at 16 and 24
      weeks. The concentrations of plasma leucine and isoleucine were significantly
      high (p<0.05) at 16 weeks. It was clear that the concentrations of plasma BCAA in
      foals and mares were at different levels at various times after birth. Since
      mares and foals were kept in health during this study, we could get the base data
      of the concentrations of BCAA in plasma of healthy foals and mares from birth to
      24 weeks.

PMID- 20046031
TI  - Pathological and microbiological studies of Japanese Hare (Lepus brachyurus
      angustidens) naturally infected with Francisella tularensis subsp. holarctica.
AB  - An adult male hare (Lepus brachyurus angustidens) was discovered in a moribund
      condition in the bush in the mountains of Aomori prefecture in Japan. Upon gross
      inspection, many ticks were found on the neck and the external ear regions, and
      more than half the ticks contained blood in the intestine. The skin around the
      tick bite wounds was alopecic and mildly thickened. At necropsy, enlargement of
      the cervical lymph nodes and spleen were observed. Histologically, acute
      necrotizing splenitis, lymphadenitis, hepatitis, pneumonia, myelitis,
      adrenalitis, and encephalitis with bacterial organisms were observed. The
      cutaneous lesions were chronic and cysts had formed in the areas marked by tick
      bites. Immunohistochemically, the organisms in the skin, liver, spleen, lymph
      nodes, lungs, adrenal glands, brain, bone marrow, and ticks were positive for F.
      tularensis antigen. Microbiological and polymerase chain reaction results were
      consistent with F. tularensis subsp. holarctica. Because the cutaneous lesions
      were more chronic than those in the visceral organs and F. tularensis was
      detected in the ticks, we inferred that F. tularensis was transmitted to the hare
      via tick bites.

PMID- 20046032
TI  - Fluorometric method for measuring plasma tartrate-resistant acid phosphatase
      isoform 5b and its application in cattle.
AB  - This study determined the appropriate biochemical assay for measuring plasma
      tartrate-resistant acid phosphatase isoform 5b (TRAP5b) activity; this
      information is important to clarify the relationship between plasma TRAP5b and
      known biochemical bone markers in cattle. When plasma TRAP5b was measured using
      fluorometric and spectrophotometric methods, hemolysis products in plasma did not
      affect the former method. In plasma from healthy cattle, there was a good
      correlation (r=0.66) between the 2 methods. In age-related profiles, plasma
      TRAP5b (r=-0.53), hydroxyproline (HYP, r=-0.56) and bone-specific alkaline
      phosphatase (BALP, r=-0.44) showed significant negative correlations with age;
      these three parameters decreased until 4 or 5 years of age and then remained
      constant. There were significant correlations between TRAP5b and HYP (r=0.83) or
      BALP (r=0.83). Our results show that the fluorometric assay can be performed with
      a high degree of precision and reproducibility without interference from
      hemolysis, and that the age-related changes in plasma TRAP5b, HYP, and BALP
      constitute additional background values for clinical guidance in bovine medicine.

PMID- 20046033
TI  - Development of vasoactive intestinal polypeptide-immunoreactive nerves in the
      major cerebral arteries of the quail anterior circulation.
AB  - Development of cerebral perivascular nerves immunoreactive for vasoactive
      intestinal polypeptide (VIP) was investigated in the Japanese quails, using
      immunohistochemistry and quantitative analysis. VIP-immunoreactive (VIP-IR)
      nerves supplying the anterior circulation appeared on the cerebral carotid artery
      (CCA) at embryonic day 10 and on the cerebroethmoidal artery (CEA) after
      hatching. Nerves from the CCA increased greatly in number and spread
      progressively during successive embryonic stages, while those from the CEA were
      sparse all through the post-hatching stages, mostly remained limited to this
      vessel wall. The distribution of VIP-IR nerves to the respective major arteries
      of the anterior circulation from the two vascular routes was basically similar
      among post-hatching day (P) 15, P20, P30 and P50. Likewise, no clear statistical
      difference was observed with regard to the nerve density of the corresponding
      arteries in the four age groups. These findings suggest that VIP-IR innervation
      of the quail anterior circulation usually attains its mature pattern at the third
      week after hatching.

PMID- 20046034
TI  - Fibrodysplasia ossificans progressiva in a Maine Coon cat with prominent
      ossification in dorsal muscle.
AB  - A one-year and six-month-old female Maine Coon cat presented with skin problems
      and paravertebral induration with a history of seven months. Survey radiographs
      and computed tomography revealed prominent calcifications in both sides of
      cervical, thoracic and lumbar vertebrae and soft tissue in femoral regions, below
      knee regions and in brachial regions. Histopathological findings from muscle
      biopsy samples showed connective tissue proliferation around adjacent skeletal
      muscle, cartilage formation and endochondral ossification. On the basis of these
      findings, this feline patient was diagnosed with fibrodysplasia ossificans
      progressiva (FOP). The most prominent signs observed in this FOP case were
      significant calcifications of dorsal muscle and presentation of cutaneous signs
      at the early stage.

PMID- 20046035
TI  - Identification and characterization of CYP2B6 cDNA in cynomolgus macaques (Macaca
      fascicularis).
AB  - Cytochrome P450 2B6 (CYP2B6), an important drug-metabolizing enzyme, is involved
      in the metabolism of prescribed drugs in humans. Despite its importance, cDNA for
      a CYP2B6 ortholog has not been identified and characterized in cynomolgus
      macaques, which are frequently used in preclinical studies. In this study, cDNA
      highly homologous to human CYP2B6 was cloned from the cynomolgus macaque liver.
      This cDNA contained an open reading frame of 491 amino acids and functional
      domains characteristic for CYP protein, such as substrate recognition sites and a
      heme-binding region. Cynomolgus CYP2B6 was expressed predominantly in the liver
      with some extra-hepatic expression among 10 tissues. Moreover, cynomolgus CYP2B6
      revealed activities toward testosterone 16beta-hydroxylation and bupropion
      hydroxylation. These results suggest that cynomolgus CYP2B6 has a functional role
      in the liver.

PMID- 20046036
TI  - Spontaneous Yersiniosis due to Yersinia pseudotuberculosis serotype 7 in a
      squirrel monkey.
AB  - A captive male Bolivian squirrel monkey (Saimiri boliviensis) of less than 1 year
      of age died following diarrhea and debilitation on the day of death. At necropsy,
      necrotizing enteritis accompanied with enlarged Peyer's patches, solitary
      lymphatic follicles and mesenteric lymph nodes, and multiple yellowish-white
      nodules in the spleen and liver were found. Histopathologically, these lesions
      were necrotizing inflammation containing Gram-negative bacilli. Yersinia
      pseudotuberculosis serotype 7 was isolated from the spleen and liver. The virF
      gene, which is an essential virulent plasimid (pYV) in pathogenic Y.
      pseudotuberculosis isolates, and the ypmA gene, which is a superantigenic toxin,
      were detected in the isolates. This is the first report of a fatal case of
      Yersinia pseudotuberculosis 7 infection in the world.

PMID- 20046037
TI  - Detection of antibody to canine distemper virus in wild raccoons (Procyon lotor)
      in Japan.
AB  - Canine distemper virus (CDV) causes a lethal disease among members of the
      Carnivora. To clarify the distribution of CDV in wild animals, we examined 106
      raccoon sera collected from two prefectures in Japan, Hyogo and Osaka, from 2005
      to 2007. Among them, 34 raccoons (32.1%) possessed a virus-neutralizing (VN)
      antibody to KDK-1 strain (genotype Asia-1). There was no significant difference
      in seroprevalence of CDV regardless of places, gender, and body weights. In
      Hyogo, a geometric mean of VN titers to KDK-1 was significantly higher than that
      to Onderstepoort (vaccine strain), indicating that KDK-1-like CDV different from
      vaccine strain might have spread among raccoon population in Hyogo. In
      conclusion, CDV is epidemic among feral raccoons in Japan, suggesting that CDV
      might have been spreading among Japanese wild animals.

PMID- 20046038
TI  - Bovine stillbirth due to Nocardia farcinica.
AB  - A stillborn calf at 259 days of gestation was examined. The dam showed no
      clinical signs of disease, and the stillbirth was occurred sporadically and were
      characterized by focal necrosis surrounded by infiltration of the cells such as
      macrophages and multinucleated giant cells. The lesions were observed
      systemically. The hyphae were visible by Grocott's stain and they were positive
      by immunohistochemical stain using serum of a rabbit immunized with the isolated
      organism. The isolated bacteria were determined to be Nocardia farcinica by
      bacteriological and molecular analysis and we confirmed that the stillbirth was
      caused by infection with and proliferation of Nocardia farcinica. This is the
      first report of a bovine stillbirth caused by this organism.

PMID- 20046039
TI  - First case report of histoplasmosis in a cat in Japan.
AB  - Cytological, histopathological and immunohistochemical examinations were carried
      out on a presumed 10-year-old Japanese cat showing vomiting and emaciation. On
      cytologic examination of the mass of the upper abdominal cavity, many yeast-like
      organisms were detected in the macrophages. At necropsy, the upper part of colon
      was markedly dilated with a thickened wall. The lung did not show significant
      changes. Histologically, severe necrotic and granulomatous lesions were observed
      in the colon. In the colonic lesion, the cytoplasm of the macrophages contained
      yeast-like organisms with irregularly shaped dots, and the cell walls of these
      organisms were stained black by Grocott-Gomori methenamine-silver stain.
      Immunohistochemically, they were found to be positive for anti-histoplasma yeast
      antibody. This is the first report of feline histoplasmosis in Japan.

PMID- 20046040
TI  - Sensitivity for the detection of a clonally rearranged antigen receptor gene in
      endoscopically obtained biopsy specimens from canine alimentary lymphoma.
AB  - Canine alimentary lymphoma is currently diagnosed on the basis of findings of
      cytological or histopathological examination. However, it is often difficult to
      histopathologically distinguish alimentary lymphoma from lymphocytic-plasmacytic
      enteritis. Recently, the application of polymerase chain reaction for antigen
      receptor gene rearrangement (PARR) has been reported. In the present study, we
      assess the sensitivity of PARR analysis in diagnosing canine alimentary lymphoma
      using endoscopically obtained biopsy specimens from 12 dogs that were
      histopathologically diagnosed as having lymphoma. The sensitivity of PARR
      analysis in diagnosing alimentary lymphoma was found to be 66.7%, which was lower
      than that of other lymphoid malignancies. A combination of histipathological
      examination and findings of PARR analysis may improve the diagnostic accuracy.

PMID- 20046041
TI  - Phylogenetic analysis of the 16S rRNA gene of Anaplasma species detected from
      Japanese serows (Capricornis crispus).
AB  - Nineteen blood samples collected from free-living Japanese serows, Capricornis
      crispus, between 2006 and 2008 in Iwate prefecture were examined for the
      anaplasma infection by PCR amplification of a part of the 16S rRNA gene. Ten
      (52.6%) out of the 19 samples produced a visible band in electrophoresed agarose
      gels. Positive PCR products were subjected to DNA sequencing. We found the
      nucleotide sequences were identical. Almost entire length of the 16S rRNA gene
      for a representative stain was then sequenced. We found the nucleotide sequence
      of the 16S rRNA gene distinct from previously established Anaplasma species in
      phylogenetic analysis. Our data first indicated that anaplasma infection occurred
      continuously among the free-living Japanese serow populations in northern Japan.

PMID- 20046042
TI  - Atypical vimentin expression in a feline salivary gland adenocarcinoma with
      widespread metastases.
AB  - We report herein a feline salivary gland adenocarcinoma with widespread
      metastases to draining lymph nodes, liver and lung, as well as an unusual
      metastasis to the spleen. Histologically, the primary salivary gland tumor
      consisted of low columnar to polygonal epithelial cells forming tubules and
      trabeculae. The spleen was infiltrated with sheets of poorly differentiated large
      round cells. Interestingly, morphologic change in epithelial cells was
      accompanied with the acquisition of vimentin intermediate filaments, a feature
      particularly evident in the splenic metastasis. This study highlights the role of
      epithelial cell plasticity during carcinogenesis and metastasis.

PMID- 20046043
TI  - Multiple routes of entry for Escherichia coli causing colibacillosis in
      commercial layer chickens.
AB  - Colibacillosis associated with salpingitis occurred in a layer chicken flock on a
      commercial egg-producing farm in Japan. An increase in mortality was observed
      when the birds were at 62 weeks of age and reached 0.89% at 68 weeks of age.
      Postmortem examinations revealed pericarditis, perihepatitis, airsacculitis, and
      reproductive tract lesions in 4 affected birds at 69 weeks of age. Analysis of
      pulse-field gel electrophoresis (PFGE) patterns and putative virulence genes of
      22 E. coli isolates obtained from the affected birds demonstrated that isolates
      from liver, heart, and the surface of the reproductive tract of one bird were
      genetically unrelated with those recovered from the lumen of the oviduct. In the
      other birds, isolates from liver, heart, and reproductive tract lesions were
      closely related to each other. These findings suggest that salpingitis in the
      former bird may be caused by ascending infection of the oviduct from the cloaca
      and salpingitis in the remaining birds may occur as part of systemic infection.

PMID- 20046044
TI  - Molecular cloning and sequencing of the cDNAs encoding the bat interleukin (IL)
      2, IL-4, IL-6, IL-10, IL-12p40, and tumor necrosis factor-alpha.
AB  - This is the first report on the cDNA sequences of bat interleukin (IL)-2, IL-4,
      IL-6, IL-10, IL-12 p40, and tumor necrosis factor (TNF)-alpha. The cDNAs of bat
      IL-2, IL-4, IL-6, IL-10, IL-12 p40, and TNF-alpha comprise 459, 405, 624, 537,
      990, and 699 base pairs respectively. Moreover, each of the cDNAs of bat IL-2, IL
      4, IL-6, IL-10, IL-12 p40, and TNF-alpha contain a single open reading frames
      encoding 152, 134, 207, 178, 329, and 232 amino acids, respectively. The
      comparison of bat cytokines with Perrissodactyla (horse), Carnivora (dog and
      cat), and Cetartiodactyla (cattle and pig) orthologs revealed a high degree of
      homology. Although the N-terminal amino acids and cysteine residues are highly
      conserved in each mature cytokine, the deduced N-linked glycosylation sites vary
      across species.

PMID- 20046046
TI  - Pleiotropic actions of Helicobacter pylori vacuolating cytotoxin, VacA.
AB  - Helicobacter pylori produces a vacuolating cytotoxin, VacA, and most virulent H.
      pylori strains secrete VacA. VacA binds to two types of receptor-like protein
      tyrosine phosphatase (RPTP), RPTPalpha and RPTPbeta, on the surface of host
      cells. VacA bound to RPTPbeta, relocates and concentrates in lipid rafts in the
      plasma membrane. VacA causes vacuolization, membrane anion-selective channel and
      pore formation, and disruption of endosomal and lysosomal activity in host cells.
      Secreted VacA is processed into p33 and p55 fragments. The p55 domain not only
      plays a role in binding to target cells but also in the formation of oligomeric
      structures and anionic membrane channels. Oral administration of VacA to wild
      type mice, but not to RPTPbeta knockout mice, resulted in gastric ulcers, in
      agreement with the clinical effect of VacA. VacA with s1/m1 allele has more
      potent cytotoxic activity in relation to peptic ulcer disease and appears to be
      associated with human gastric cancer. VacA activates pro-apoptotic Bcl-2 family
      proteins, and induces apoptosis via a mitochondria-dependent pathway. VacA can
      disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing
      production of IL-8 and PGE(2), and PI3K/Akt, suppressing GSK-3beta activity. VacA
      has immunomodulatory actions on T cells and other immune cells, possibly
      contributing to the chronic infection seen with this organism. H. pylori
      virulence factors including VacA and CagA, which is encoded by cytotoxin
      associated gene A, along with host genetic and environmental factors, constitute
      a complex network to regulate chronic gastric injury and inflammation, which is
      involved in a multistep process leading to gastric carcinogenesis.

PMID- 20046047
TI  - Monolayer culture systems with respiratory epithelial cells for evaluation of
      bacterial invasiveness.
AB  - Pseudomonas (P.) aeruginosa is a major opportunistic pathogen especially in
      immunocompromised patients. To evaluate the invasiveness of respiratory
      pathogens, we developed monolayer culture systems and examined the degree of
      invasion by P. aeruginosa and invasive Salmonella (S.) typhimurium strains using
      human respiratory cell lines: A549 (derived from lung cancer), BEAS-2B (normal
      bronchial epithelium), and Calu-3 (pleural effusion of a patient with
      adenocarcinoma of the lung). Cells were seeded into filter units containing 0.33
      cm(2) filter membranes with 3.0 microm pores, and were incubated at 37 degrees C
      under 5% CO(2) for 4-10 days. By monitoring the trans-monolayer electrical
      resistance (TER), we judged that BEAS-2B cells (TER values: 436.2 +/- 16.8 to
      628.8 +/- 66.3 Omega cm(2)) and Calu-3 cells (TER values: 490.5 +/- 25.2 to 547.8
      +/- 21.6 Omega cm(2)) formed monolayers with tight junctions, but not A549 cells.
      On day 8 of culture, monolayer cultures were infected with bacteria, and the
      number of microorganisms penetrating into the basolateral medium was counted.
      Wild-type P. aeruginosa PAO1 (PAO1 WT) and S. typhimurium SL1344 were detected in
      the basolateral medium of BEAS-2B monolayer system by 3 h after inoculation,
      while only P. aeruginosa PAO1 WT was detected in the basolateral medium of Calu-3
      monolayer, indicating poor invasiveness of S. typhimurium SL1344 in the Calu-3
      system. These findings suggest that BEAS-2B or Calu-3 monolayer system could be
      useful for evaluating the invasiveness of respiratory pathogens. Because of the
      difference in bacterial invasiveness, we may need to choose a suitable cell
      system for each target pathogen.

PMID- 20046048
TI  - High numbers of interferon-gamma-producing T cells and low titers of anti
      tuberculous glycolipid antibody in individuals with latent tuberculosis.
AB  - Latent tuberculosis infection (LTBI) is defined as an infection with
      Mycobacterium tuberculosis (MTB) without clinical, bacteriological, or
      radiological findings, and its early diagnosis is essential for eradication of
      tuberculosis. To identify LTBI, we measured the numbers of interferon-gamma
      producing T cells, based on the ELISPOT assay, and the antibody titers in the
      sera to tuberculous glycolipid antigen (TBGL-Ab). Seventeen culture-confirmed TB
      patients, 13 controls from TB endemic areas (EC) and 13 controls from TB non
      endemic areas (NEC) were enrolled. Peripheral blood mononuclear cells (2.5 x
      10(5) per well) were cultured on plates precoated with antibody against
      interferon-gamma. ELISPOT response was defined as positive when the MTB-specific
      antigen-containing wells showed at least 6 spots and twice numbers of spots than
      negative control wells. ELISPOT responses were positive in 15 (88%), 8 (62%) and
      4 (31%) subjects of TB, EC and NEC groups, respectively. The ELISPOT data differ
      between TB and NEC groups (p < 0.01) but not between TB and EC groups. In
      contrast, TBGL-Ab titers were elevated (> 2.0 U/ml) in 12 TB patients (71%), but
      only in one subject (8%) each from EC and NEC groups. These results indicate the
      high prevalence of LTBI in EC. In conclusion, LTBI is associated with positive
      ELISPOT assay and the low titer of TBGL-Ab, while positive results both in
      ELISPOT and TBGL-Ab assays indicate active TB. The low titer of TBGL-Ab is a
      helpful marker to identify LTBI in ELISPOT-positive individuals in TB endemic
      areas.

PMID- 20046049
TI  - Different clinical presentation in siblings with mitochondrial acetoacetyl-CoA
      thiolase deficiency and identification of two novel mutations.
AB  - Mitochondrial acetoacetyl-CoA thiolase (T2) catalyzes 2-methylacetoacetyl-CoA
      cleavage into acetyl-CoA and propionyl-CoA in isoleucine catabolism and
      interconversion between acetyl-CoA and acetoacetyl-CoA in ketone body metabolism.
      T2 deficiency is a rare metabolic disease of autosomal recessive inheritance. The
      disorder is characterized by intermittent ketoacidotic episodes. The onset of
      clinical symptoms is in the infant or toddler period. The frequency of episodes
      declines with age, stopping before adolescence. Here we report two siblings with
      this disorder. The proband (GK65) is a French girl born from non-consanguineous
      parents. She presented several ketoacidotic episodes with 5 hospitalizations from
      age 2 to 4 years, the first of them complicated by ketoacidotic coma. Minor
      episodes, which are generally provoked by infections or high protein intake,
      still persist at age of 16 years. Molecular analysis of the T2 gene has revealed
      the compound heterozygosity of c.578T>C (M193T) and IVS8+5g>t. The latter
      mutation results in skipping of exon 8. In contrast, the younger brother (GK65b)
      had a unique ketoacidotic crisis at the age of 6 years that is the oldest-age
      first crisis among T2-deficient patients reported thus far. Despite the mild
      phenotype, he carried the same T2 gene mutations as his sister (GK65).
      Furthermore, T2 catalytic activity and T2 protein were not detected in the
      fibroblasts derived from GK65 and GK65b. In conclusion, the siblings with the
      same T2 gene mutations present different clinical severity. Diagnostic testing
      for asymptomatic siblings is important in the management of T2-deficient
      families.

PMID- 20046050
TI  - Establishing a model of supratentorial hemorrhage in the piglet.
AB  - The most common site of hemorrhage is the basal ganglia, which exhibits the
      obvious neurological deficits. In the present study, we aimed to develop a model
      of supratentorial intracerebral hemorrhage (ICH) with neurological deficits in
      piglets (6.0 to 8.8 kg). A pediatric urinary catheter with two passages and one
      balloon was introduced through a burr hole into the right striatum. All the
      animals received balloon inflation, which was performed by injecting 2.5 ml
      saline into the balloon through one passage. Then each piglet in experimental
      group (n = 18) received an injection of 1.0-ml autologous arterial blood through
      the other passage over 2 min and maintained for 5 min. Then, additional 1.5-ml
      blood was injected over 15 min. Piglets in control group (n = 6) received only
      balloon inflation without blood injection. CT scanning was performed immediately
      after surgery. A deep hematoma was successfully induced in 16 out of 18 piglets
      and the hematoma volume was 1.74 +/- 0.22 ml (n = 5) at 24 hours after surgery.
      All the piglets with hematoma had behavioral deficits (lame or could not walk) at
      24 hours. Tissue damages, such as cell swelling, necrosis and demyelization,
      appeared at 24 hours in the brain tissues, adjacent to the hematoma, and was
      aggravated at 48 hours and ameliorated at 7 days after hematoma induction. In
      conclusion, we have established a simple model of supratentorial ICH in piglets
      with marked neurological deficits, which is suitable for study of the
      pathophysiology and treatment of ICH.

PMID- 20046051
TI  - The risk of penetration or aspiration during videofluoroscopic examination of
      swallowing varies depending on food types.
AB  - Videofluoroscopic examination of swallowing (VF) is the gold standard in
      diagnosis and management of dysphagia. During VF, the patient ingests radiopaque
      foods and liquids, and oral, pharyngeal, and esophageal stages of swallowing
      physiology are observed and evaluated. Aspiration is defined as passage of
      materials through the vocal folds, and laryngeal penetration is defined as
      passage of materials into the larynx, but not through the vocal folds. In this
      study, we compared the risk of laryngeal penetration or aspiration during VF
      using various liquid volumes and food consistencies. Between January 2006 and
      September 2008, 229 patients with suspected dysphagia each were fed at least 2
      out of 6 types of liquids or foods during VF in an upright posture without
      compensatory maneuvers. The 6 types were pudding-thick barium of 4 ml (PD), thin
      liquid barium of 4 ml (LQ4) and 10 ml (LQ10), one swallow of thin liquid barium
      from a cup (CUP), corned beef hash (8 g) with barium (CB), and a two-phase
      mixture of corned beef hash (4 g) with barium and thin liquid barium of 5 ml
      (MX). The paired comparisons revealed that laryngeal penetration risk increased
      in the following order: PD, CB, LQ4, LQ10, MX and CUP, while aspiration risk
      after PD increased in the following order: CB, LQ4, LQ10, CUP and MX. Thus, risk
      of laryngeal penetration or aspiration varies, depending on food types. In
      conclusion, risk of aspiration is highest with the two-phase food, and multi
      textured foods should be used with caution in individuals with dysphagia.

PMID- 20046052
TI  - Trends in antimicrobial susceptibility of Streptococcus pneumoniae in the Tohoku
      district of Japan: a longitudinal analysis from 1998 to 2007.
AB  - Streptococcus pneumoniae is a common cause of respiratory tract infections
      (RTIs). The prevalence of Streptococcus pneumoniae strains with reduced
      susceptibility to antimicrobial agents has dramatically increased worldwide.
      Susceptibility to nine antimicrobial agents and serotypes were determined among
      1,644 Streptococcus pneumoniae strains isolated from patients with RTIs in the
      Tohoku district of Japan from October to December every year from 1998 to 2007.
      The prevalence of penicillin G-nonsusceptible Streptococcus pneumoniae (PNSP)
      strains increased gradually from 48.5% in 1998, reached a statistical peak in
      2004 (65.1%) and then decreased to 51.5% in 2007. Streptococcus pneumoniae
      strains with each serotype 3, 6, 19 and 23 were constantly detected, and the
      distribution of these serotypes in PNSP strains did not significantly change
      during the study period. A trend of Streptococcus pneumoniae strains
      nonsusceptible to other beta-lactams tested was similar to that of PNSP strains,
      except for cefditoren, to which the resistance rate was < 20% throughout the
      analysis period. The prevalence of strains nonsusceptible to erythromycin and
      minocycline were consistently > 60%. Almost all penicillin G-resistant
      Streptococcus pneumoniae (PRSP) strains were resistant to both erythromycin and
      minocycline throughout the analysis period. The prevalence of strains resistant
      to fluoroquinolones tested were < 3% over the study period. Our longitudinal
      surveillance demonstrated for the first time that decreased prevalence of both
      beta-lactam- and multidrug-resistant strains has been occurring since 2004 in a
      region of Japan. Careful monitoring of antimicrobial susceptibility of
      Streptococcus pneumoniae should be continued.

PMID- 20046053
TI  - Low expression of T-cell co-stimulatory molecules in bone marrow-derived
      dendritic cells in a mouse model of chronic respiratory infection with
      Pseudomonas aeruginosa.
AB  - Pseudomonas (P.) aeruginosa frequently colonizes the respiratory tract of
      patients with chronic respiratory tract infections such as diffuse
      panbronchiolitis (DPB). The number of dendritic cells (DCs) that play a central
      role in immune functions as antigen-presenting cells is reportedly increased in
      the bronchiolar tissues of patients with DPB. However, the functions of DCs in
      chronic P. aeruginosa respiratory tract infection have not been defined. Here, we
      assessed the functions of DCs and the effect of macrolide antibiotics that are
      therapeutic agents for DPB, in a murine model of DPB caused by P. aeruginosa.
      Mice were intubated with either P. aeruginosa- or saline-precoated tubes for 80
      days. Thereafter, the expression of T-cell co-stimulatory molecules (CD40, CD80,
      and CD86) and cytokine secretion (interleukin (IL)-10, IL-6, IL-12p40, and tumor
      necrosis factor (TNF)-alpha) on bone marrow-derived DCs stimulated by
      lipopolysaccharide were examined by flow cytometry and enzyme-linked
      immunosorbent assays. The expression of co-stimulatory molecules was
      significantly decreased in mice infected with P. aeruginosa compared to the
      saline-treated control mice, but production of these cytokines did not
      significantly differ between the two groups. Pretreatment with clarithromycin ex
      vivo decreased CD40 expression on DCs obtained from P. aeruginosa-infected mice
      and also decreased the production of IL-6, IL-12p40 and TNF-alpha by DCs. These
      findings suggest that chronic P. aeruginosa infection alters DC functions and
      that macrolides function as anti-inflammatory agents by modulating the functions
      of DCs in chronic P. aeruginosa infection.

PMID- 20046054
TI  - Beneficial role of periosteum in distraction osteogenesis of mandible: its
      preservation prevents the external bone resorption.
AB  - Distraction osteogenesis (DO) is a surgical process of new bone generation
      through the gradual extension of two segments of existing bone. DO is applied for
      maxillofacial surgeries to manage defects in mandibular continuity. Vertical DO
      with an oral device is often employed to augment the alveolar bone height for
      better implant anchorage for esthetic purposes or functional prosthetic
      requirements. To determine how the periosteum affects the vertical DO in
      mandibular reconstruction, we extracted the teeth and resected the alveolar parts
      of the mandible on both sides of dogs, along with removal of the surrounding
      periosteum in the right, but not left side. Three months later, box-shaped bone
      segments (vectors) were prepared from the resected alveolar part, and the
      segments were vertically elongated using a distraction device on both sides at
      0.9 mm/day for one week. The extent of bone formation after distraction was
      determined with micro-focused computed tomography and by measuring incorporation
      of tetracycline and calcein with confocal laser scanning microscopy. During the
      initial two months after distraction, new bone formation was observed more
      prominently in the left side than in the right side of mandible with the
      periosteum. However, this difference was less clear during the bone-remodeling
      period. One notable change was the reduced height of the alveolar part of the
      right-side mandible, a sign of external bone resorption, observed in two out of
      three dogs at 6-month post-consolidation. These findings suggest that
      preservation of periosteum prevents the external bone resorption during the
      vertical DO of mandible.

PMID- 20046055
TI  - Association of the G2014G genotype in estrogen receptor 1 gene with failure of
      the mifepristone-induced termination of early pregnancy.
AB  - Mifepristone is a synthetic steroid compound that has been applied to terminate
      early pregnancy for many years. However, about 15% of the women undergo failure
      in termination of early pregnancy, the causes of which remain largely unknown. We
      herein selected estrogen receptor 1 gene (ESR1) as a candidate gene to determine
      whether single nuclear polymorphisms (SNPs) in ESR1 were associated with the
      failure of mifepristone-induce abortion. The subjects recruited were 30 subjects
      that failed to abort and 60 subjects with a successful medical abortion. Three
      SNPs, T-397C (rs2234693), C325G (rs1801132), and G2014A (rs2228480), were
      analyzed by PCR, followed by restriction fragment length polymorphism (RFLP)
      analysis. The latter two polymorphic sites are located in the protein-coding
      region, but do not alter the amino acid. Among the three SNPs examined, we found
      the significant role of the G2014A polymorphism; namely, the distribution of the
      GG, AG and AA genotypes was different between the failure group and the success
      group. The frequency of the GG (G2014G) genotype was higher in the failure group
      (86.7%) than that in the success group (60.0%) (p = 0.030), while the frequency
      of the G2014A heterozygote was lower in the failure group (6.7%) than in the
      success group (28.3%) (p = 0.013). Moreover, the frequency of the G allele was
      higher in the failure group (90%) and lower in the success group (10.0%) (p =
      0.013). These results indicate that the GG genotype of the G2014A polymorphism is
      associated with the risk of failure in the mifepristone-induced abortion.

PMID- 20046056
TI  - Development of a training method for weightless environment using both electrical
      stimulation and voluntary muscle contraction.
AB  - Extreme skeletal muscle atrophy is rampant in astronauts exposed to extended
      periods of microgravity (muG), and it is one of the main problems in human space
      exploration. A "Hybrid training" (HYB) method utilizing combined electrical
      stimulation and voluntary muscle contraction has been developed as a possible
      solution. A wearable HYB device and a virtual reality (VR) system were developed
      for use in space, and were verified at muG generated by parabolic flight (PF). A
      36-year-old male subject performed HYB of reciprocal flexion and extension as a
      knee joint exercise training in a seated position at 1G, 2G and muG. The wearable
      HYB device and VR system developed for the study functioned well during the
      flight. However knee extension was insufficient at 1G and 2G, and the maximum
      knee extension angles at 1G and 2G were smaller than at muG. The extension
      velocity in the latter half of each motion was slower than in the first half at
      1G and 2G, but no difference in velocity was observed at muG. The subject could
      extend the knee joint sufficiently and keep a constant extension velocity,
      because his legs were weightless at muG. The congruity between the subject's
      actual joint motions and instructed joint motions during muG was improved, when
      VR was employed with or without body fixation; accordingly, the subject was able
      to perform the desired joint motion. The VR system improved HYB exercise
      performance at muG during PF. HYB is considered a useful training method for
      future human space exploration.

PMID- 20046057
TI  - [Advanced approaches to anti-aging --use of aging model animals--].

PMID- 20046058
TI  - [Antiaging research using klotho mice].
AB  - The klotho mouse shows multiple phenotypes resembling human aging caused by the
      mutation of a single gene. This mutation is caused by the insertion of ectopic
      DNA into the regulatory region of the alpha-klotho gene. The alpha-klotho gene
      encodes a type I membrane protein that is expressed predominantly in the kidney
      and brain. As a result of a defect in alpha-klotho gene expression, the klotho
      mouse exhibits multiple age-associated disorders, such as arteriosclerosis,
      osteoporosis, pulmonary emphysema and short life span. However, the mechanism by
      which the alpha-klotho gene product suppresses the aging phenomena has not been
      identified. Analysis of the pathophysiology of klotho mice is expected to give
      clues not only to understanding the mechanisms of individual diseases associated
      with aging but also the molecular mechanisms during human aging. We previously
      reported that the aberrant activation of mu-calpain is caused by the alpha-klotho
      mutation, and such change leads to degradation of cytoskeletal elements. Similar
      phenomena were observed in normal aged mice. Such deterioration may trigger
      tissue abnormalities in klotho mice and aged mice, but klotho protein may
      suppress these processes. We will summarize the function of alpha-klotho protein
      based on our research on the relationship between proteolysis and age-related
      disorders and the recent advanced researches.

PMID- 20046059
TI  - [Anti-aging studies on the senescence accelerated mouse (SAM) strains].
AB  - Senescence accelerated mouse (SAM), a murine model of accelerated senescence, was
      established by Toshio Takeda and colleagues. SAM consists of series of SAMP
      (prone) and SAMR (resistant) lines. All SAMP lines (from SAMP1 to SAMP11) are
      characterized by accelerated accumulation of senile features, earlier onset and
      faster progress of age-associated pathological phenotypes, such as amyloidosis,
      impaired immune response, senile osteoporosis and deficits in learning and
      memory. These SAMP lines are useful for evaluation of putative anti-aging
      therapies. For example, SAMP1 line is used to study the anti-aging effect of the
      antioxidant containing foods and various anti-oxidants, such as coenzyme Q10,
      vitamin C, lycopene. SAMP8 line exhibiting an early onset of impaired learning
      and memory is often used for test strategies for therapeutic intervention of
      dementia of early onset. SAMP6 is used as an animal model for developing new
      strategies for the treatment of osteoporosis in humans. Various lines of SAM (P1,
      P6, P8, P10 and R1) are now commercially available for research. In this review,
      I will briefly introduce various usages of SAM in anti-aging research.

PMID- 20046060
TI  - [Anti-aging research using Mn-SOD conditional knockout mice].
AB  - Manganese superoxide dismutase (Mn-SOD) is a mitochondrial enzyme that converts
      toxic O(2)(-) to H(2)O(2). Previous studies have reported that a systemic
      deficiency in Mn-SOD causes neonatal lethality in mice. Therefore, no mouse model
      is available for the analysis of the pathological role of O(2)(-) injuries in
      adult tissues. To explore an adult-type mouse model, we generated tissue-specific
      Mn-SOD conditional knockout mice using a Cre-loxp system. First, we generated
      liver-specific Mn-SOD-deficient mice by crossbreeding with albumin-Cre transgenic
      mice. Mn-SOD proteins were significantly downregulated in the liver of liver
      specific Mn-SOD knockout mice. Interestingly, the mutant mice showed no obvious
      morphological abnormalities or biochemical alterations in the liver, suggesting a
      redundant or less important physiological role for Mn-SOD in the liver than
      previously thought. Next, we generated heart/muscle-specific Mn-SOD-deficient
      mice by crossbreeding with muscle creatine kinase-Cre transgenic mice. The mutant
      mice developed progressive dilated cardiomyopathy with specific molecular defects
      in mitochondrial respiration. Furthermore, skeletal muscle-specific Mn-SOD
      deficient mice that had been generated by crossbreeding with human skeletal actin
      Cre transgenic mice developed a severe physical disturbance associated with
      impaired cellular ATP metabolism. These results imply that the superoxide
      generated in mitochondria plays a pivotal role in the development and progression
      of pathologies in the heart and skeletal muscle, but not in the liver. In
      conclusion, we successfully generated various tissue-specific Mn-SOD conditional
      knockout mice that provide useful tools for the analysis of various oxidative
      stress-associated diseases.

PMID- 20046061
TI  - [Anti-aging research using SMP30/GNL knockout mice].
AB  - Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein
      in the rat liver, the expression of which decreases with aging. Recently, we
      identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of
      animal species. GNL was a key enzyme which involved in vitamin C biosynthesis,
      and the essential role of SMP30 in this synthetic process was verified by a
      nutritional study. SMP30 knockout mice developed symptoms of scurvy when fed a
      vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C
      biosynthesis. Moreover, SMP30 knockout mice were shorter in life span than the
      wild type when fed autoclaved mouse chow contained approximately 55 mg/kg of
      vitamin C, which we now know contains too little vitamin C to maintain normal
      levels of vitamin C in tissues. These results demonstrate that vitamin C
      deficiency shortens longevity, that is, vitamin C deficiency accelerates aging.

PMID- 20046062
TI  - [Analysis of aging-related oxidative stress status in normal aging animals and
      development of anti-aging interventions].
AB  - Since Harman proposed the "free-radical theory of aging", oxidative stress is
      postulated to be a major causal factor of senescence. Accumulation of oxidative
      stress-induced oxidatively modified macromolecules including protein, DNA, and
      lipid, were found in tissues during the aging process. However, it is not
      necessarily clear which factor is more critical for an increase in endogenous
      reactive oxygen and/or decrease in antioxidative defense, to the age-related
      increase in oxidative damage. To clarify the production of reactive oxygen
      increasing with age, we examined reactive oxygen-dependent chemiluminescent (CL)
      signals in ex-vivo brain slices prepared from different aged animal brain during
      hypoxia-reoxygenation treatment using a novel photonic imaging method. CL signal
      was intensified during reoxygenation. The signals in SAMP10 (short life strain)
      and SAMR1 (control) brain slices increased with aging. The slope of increase of
      CL intensity with age in P10 was steeper than those in R1. Age-dependent increase
      of CL intensity was also observed in C57BL/6 mouse, Wistar rat, and pigeon.
      However, SOD activity in brain was not changed with age. These results suggest
      that reactive oxygen production itself increase with aging. The rate of age
      related increase of CL intensity was inversely related to the maximum life span
      of the animals. We speculate that reactive oxygen may be a kind of signal for
      aging and its levels in tissue may determine the aging process and life span. To
      decelerate the age-related increases of reactive oxygen production is expected as
      a potent strategy for anti-aging interventions.

PMID- 20046063
TI  - [Development of a technology platform for novel drug discovery aimed at
      regulating biological function].

PMID- 20046064
TI  - [Artificial transcription factors based on multi-zinc finger motifs].
AB  - Artificial transcription factors targeting any desired genes are very attractive
      from the standpoint of regulating biological functions for life science studies
      and clinical applications. In order to generate such transcription factors,
      specific DNA binding domains are required to address a single site for each gene
      promoter. C(2)H(2) type zinc finger motif is one of the best frameworks to create
      new artificial DNA binding proteins for the following features: the zinc finger
      motif can recognize three bases DNA, be tandemly repeated by covalent linkage,
      and work as a monomer. Taking advantage of these features, manifold zinc finger
      proteins targeting various DNA sequences have been created so far. For
      application to a target in sequences as complex as the human genome, the
      significantly strict specificity in DNA binding must be required. Conjugating
      multiple fingers (multi-zinc fingers) enables to recognize longer sequences which
      are sufficient for addressing a single site in the human genome, whereas it has
      become known that as the number of finger motifs increases, the equilibrium time
      with the target sequence is significantly longer by in vitro experiments. Our
      recent study showed that the multi-zinc finger type artificial transcription
      factor could activate the reporter gene promptly. There is much interest in
      creating gene regulators, and the artificial transcription factors based on multi
      zinc finger motifs could be a superior scaffold.

PMID- 20046065
TI  - [Enhancement of antibody-dependent cellular cytotoxicity by tandem Fc
      multimerization].
AB  - Monoclonal antibodies are being used as therapeutics for a number of cancers,
      such as leukemia, breast and colon cancers, and a lot of monoclonal antibodies
      specific for tumor-related antigens have been on clinical trials. Antibody
      dependent cellular cytotoxicity (ADCC) is one of the major mechanisms by which
      antibodies exert anti-tumor effects. ADCC occurs through interaction between the
      Fc domains of IgG antibodies bound to target cells and Fcgamma receptors on the
      surface of effector cells. In our study, a chimeric antibody, designated M-Ab,
      was constructed with the V regions from mouse anti-CD20 mAb 1F5 and the C regions
      from human IgG1 and kappa chain. Two or three Fc domains were tandemly repeated
      downstream of the C-terminus of the M-Ab to give D0-Ab (Fc dimer Ab without a
      linker), T0-Ab (Fc trimer Ab without a linker), and T3-Ab (Fc trimer Ab with a
      (GGGGS)(3) linker in front of the second and third hinge regions). Here, we show
      that Fc tandem repeat antibodies bind to all the low-affinity Fcgamma receptors
      with very potent avidities and have greatly enhanced ADCC activity. T3-Ab is
      about 100 times more potent than the parental 1F5 chimeric antibody in terms of
      both Fcgamma receptor binding and exerted ADCC activity at a 50-100 times less
      concentration as compared with the parental antibody. Thus, Fc tandem repeat
      antibodies are anticipated to be candidates for anti-tumor therapeutics and
      useful tools to elucidate the biological roles of Fcgamma receptors.

PMID- 20046066
TI  - [Application of bioactive mutant TNF alpha to a mucosal vaccine adjuvant].
AB  - A large number of emerging pathogens, such as severe acute respiratory syndrome
      (SARS), human immunodeficiency virus (HIV), and influenza virus are mucosally
      transmitted and must cross mucosal barriers to infect the host. Thus, to induce a
      maximal protective effect, it is desirable to apply vaccines by the mucosal route
      where virus infections start. Mucosal vaccines administered either orally or
      nasally have been shown to be effective in inducing antigen-specific immune
      responses at both systemic and mucosal compartments. However the mucosal antigen
      specific immune response is weak because most protein antigens can evoke only a
      weak immune response when they are applied mucosally. Therefore, one strategy to
      overcome the weakness of the immune response is a co-administration of mucosal
      adjuvant with the vaccine antigen. Unfortunately, the development of safe and
      effective mucosal adjuvant has proved to be challenging. Cytokines are promising
      adjuvants because they are human-derived safe material and display potent immune
      modulating functions. In this regards, we have created a mutant tumor necrosis
      factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and
      resistance to proteases. In this report, we examined the potential of mTNF-K90R
      as a mucosal adjuvant and evaluated its effectiveness and safety.

PMID- 20046067
TI  - [Creation of TNFR1-selective antagonist and its therapeutic effects].
AB  - Onset and exacerbation of autoimmune disease, such as rheumatoid arthritis and
      Crohn's disease would be regulated with hundreds of disease-related proteins
      changing in quality and quantity. Recently, tumor necrosis factor-alpha (TNF
      alpha) comes to be known that is the key molecule for development of the
      autoimmune diseases and recognized as the drug target which should be inhibited
      to overcome the diseases using neutilizing antibodies. Because the functions of
      TNF-alpha are regulated with the manner binding to two receptors, TNFR1 and
      TNFR2, unexpected side-effects would happen with complete inhibition or
      activation of the TNF receptor signaling. Thus, it is essential to develop a
      novel drug developing technology, which regulates the binding pattern of TNF
      alpha definitely for therapeutic purposes. In this regard, we have aimed to
      create the TNF-alpha mutant, which has selectivity for binding TNFR1 or TNFR2 and
      regulates the onset and exacerbation of inflammatory diseases. Recently, we have
      succeeded in creating several TNF-alpha mutants by phage display techniques which
      can substitute aimed amino acids to the other, randomly. In this review, we
      introduce our unique TNFR1-selective antagonist, which can only inhibit the
      function via TNFR1 correlating with the onset and exacerbation of autoimmune
      disease. This TNFR1-selective antagonist does not inhibit the host defense
      function via TNFR2. This mutant TNF-alpha did not show the increase of virus
      infection suggested that it may overcome the risk of infectious disease, which is
      a major side-effect of anti-TNF-alpha therapy. These results would provide widely
      the strategy of regulating protein function in molecular level and would show the
      attractive approach to create safe and effective medical drug reducing side
      effects.

PMID- 20046068
TI  - [Correlation of pharmacokinetic parameters with serum vancomycin concentration in
      elderly patients with malignancies].
AB  - Vancomycin (VCM) is a glycopeptide antibiotic that is generally used to treat
      methicillin-resistant Staphylococcus aureus (MRSA). Recently, it has been
      reported that VCM clearance (CL) is significantly higher in elderly patients and
      infants and children with malignancies, compared with those without malignancies.
      We have treated many patients with a variety of malignant tumors in whom serum
      VCM concentrations were found to be moderately lower during therapeutic drug
      monitoring (TDM). The aim of this study was to determine whether the presence of
      malignant tumors influences trough concentrations of VCM and VCM pharmacokinetics
      in elderly patients during treatment for MRSA infection. Comparison of the
      clinical characteristics and VCM pharmacokinetic parameters between patients with
      and without malignancies was undertaken in 49 elderly Japanese patients infected
      with MRSA. The mean trough concentration of VCM in patients with malignancies was
      significantly lower than that in patients without malignancies. Our results
      showed significantly higher values of VCM CL and volume of distribution and a
      shorter elimination half-life in patients with malignancies. Univariate logistic
      regression analysis of the pharmacokinetic parameters indicated that VCM CL
      contributed as a significant factor independent of the relation to malignant
      tumor. In conclusion, it is suggested that the therapeutic effects and side
      effects of VCM should be actively monitored using TDM, because concentrations may
      decrease when CL increases in VCM therapy for elderly patients with malignant
      tumors.

PMID- 20046069
TI  - [Preparation of orally disintegrating tablets for masking of unpleasant taste:
      comparison with corrective-adding methods].
AB  - Many orally disintegrating tablets have recently been developed to improve oral
      ingestion and usability and are widely administered clinically, resulting in
      improved quality of life for patients. Since orally disintegrating tablets
      rapidly disintegrate in the mouth, the masking of unpleasant taste is important.
      We investigated the masking of the taste of furosemide (FU) as a model drug with
      correctives and prepared orally disintegrating tablets. Using maltitol (MA) as a
      corrective, granules were prepared employing mixing, coating, and mixing/coating
      methods using a desktop granulator. Each preparation was subjected to tasting.
      The taste was masked well when granules were prepared by the mixing and
      mixing/coating methods. Tablets were prepared from these granules with mannitol
      and crystalline cellulose added as fillers. Tablets made from granules prepared
      by the mixing and mixing/coating methods showed appropriate strength and
      disintegrated rapidly. When the amount of MA was increased in the mixing method,
      the disintegration time was prolonged, and thus the amount should be determined
      considering both taste masking and disintegration property. The results showed
      that orally disintegrating tablets of insoluble drugs with an unpleasant taste
      such as FU should be prepared with the taste masked employing the methods used in
      this study.

PMID- 20046070
TI  - Preparation of orally disintegrating tablets with taste-masking function: masking
      effect in granules prepared with correctives using the dry granulation method and
      evaluation of tablets prepared using the taste-masked granules.
AB  - We investigated several methods of taste masking in the preparation of orally
      disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types
      of FU preparations were prepared: granules with maltitol (MA), granules with
      yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU
      and YO. All taste-masking granules were prepared using the dry granulation
      method. The taste of each type of preparation was evaluated. All four
      preparations markedly improved the taste of the FU tablets, but the mixing ratios
      of the correctives did not affect the masking effect. No difference in masking
      effect was found between MA and YO in the physical mixtures, but the masking
      effect in the granules with YO was superior to that of the granules with MA.
      Taste-masked FU tablets were prepared using the direct compression method;
      crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at
      the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness,
      but MA-containing tablets were harder than YO-containing tablets. The hardness of
      the tablets prepared from YO granules increased as the YO content increased. The
      most rapidly disintegrating tablets were those of YO granules prepared at a
      mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the
      tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The
      disintegration times of the tablets made from physical mixtures, in contrast,
      were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO
      or MA increased. The hardness and disintegration time of these tablets could be
      controlled by varying the compression pressure. We found that YO is more useful
      than MA in masking unpleasant tastes and confirmed that orally disintegrating
      tablets with taste-masking function can be prepared using granules of YO prepared
      using the dry granulation method as a new corrective.

PMID- 20046071
TI  - Doripenem pharmacokinetics in critically ill patients receiving continuous
      hemodiafiltration (CHDF).
AB  - Objectives of the prospective, open-label study were to investigate
      pharmacokinetics of doripenem and determine appropriate doripenem regimens during
      continuous hemodiafiltration (CHDF) in critically ill patients with renal failure
      (creatinine clearance <30 ml/min) in the intensive care unit at a university
      hospital in Japan. Six patients received intravenous (IV) administration of 250
      mg of doripenem every 12 or 24 hours during CHDF (dialysis rate, 500 ml/h;
      hemofiltration rate, 300 ml/h) via a polysulfone hemofilter. Doripenem
      concentrations in pre- and post-membrane blood (plasma) samples collected at
      specified times during one dosing interval were measured in order to calculate
      pharmacokinetic parameters and clearance via hemodiafiltration. Mean half-life
      (+/-standard deviation) of doripenem was 7.9+/-3.7 hours. Total body clearance of
      doripenem was 58.0+/-12.7 ml/min, including clearance of 13.5+/-1.6 ml/min via
      CHDF. An IV dose of 250 mg of doripenem every 12 hours during CHDF provided
      adequate plasma concentrations for critically ill patients with renal failure,
      without resulting in accumulation upon steady-state. Thus, under the conditions
      tested, CHDF appeared to have little effect on doripenem clearance. Therefore,
      the blood level of doripenem can be satisfactorily controlled by adjustment of
      doripenem dose and dosing interval, in accordance with residual renal function in
      patients receiving CHDF.

PMID- 20046072
TI  - Prediction of incompatibility of ceftriaxone sodium with calcium ions using the
      ionic product.
AB  - The purpose of this study was to evaluate the incompatibility of ceftriaxone
      sodium with calcium-containing products using the ionic product of precipitation,
      and the measurement of insoluble microparticles using a light obscuration
      particle counter. Appropriate volumes of 2% (w/v) calcium chloride solution were
      added to 0.4-2 mg/ml ceftriaxone isotonic sodium chloride solution, to make
      solutions with a final calcium ion concentration of 1.25 mmol/l. The solutions
      were gently agitated and stored at 37 degrees C for 24 h. The number of insoluble
      microparticles with a diameter less than 10 microm in the mixed sample solution,
      determined using a light obscuration particle counter, was increased when the
      ceftriaxone concentration was > or =0.8 mg/ml. The Saturation Index (defined as
      the ratio of the ionic product to the solubility product constant) of the
      prepared mixed solution was 1.1. A white precipitate could be observed visually
      when the ceftriaxone concentration of the sample solution was 7 mg/ml; the
      Saturation Index of the solution was 9.7. The effect of the calcium source on
      incompatibility with ceftriaxone sodium was also evaluated. The numbers of
      insoluble microparticles in sample solutions made by adding calcium chloride to
      the sample were significantly higher than those made by adding calcium gluconate.
      These results suggest that ceftriaxone should not be co-administered with calcium
      containing products even if no precipitation is observed visually. There will
      still be insoluble microparticles caused by incompatibility in the sample
      solution when the Saturation Index of the solution is over 1.0.

PMID- 20046073
TI  - [Preparation of PLGA microspheres encapsulating highly concentrated glycyrrhizin
      and the bile elimination of glycyrrhizin after subcutaneous administration in
      rats].
AB  - The aim of this study was to prepare poly (lactide-co-glycolide) (PLGA)
      microspheres encapsulating highly concentrated glycyrrhizin (GZ), a hydrophilic
      drug, and to compare the release characteristics of GZ in in vitro experiments
      and GZ elimination into bile after subcutaneous administration in rats. The
      preparation was carried out based on water drying using a (w/o)/w emulsion. The
      encapsulation rate of GZ in microspheres was 76% when the GZ concentration in the
      outer water phase was equal to that in the inner water phase for the preparation
      of (w/o)/w emulsion. The release of GZ from the microspheres showed a biphasic
      zero-order profile, that is, the behavior boundary was approximately 12 h. The
      release of GZ from the microspheres at the periods of 0.5-8 h and 12-672 h was
      0.18 mg/h and 0.0012 mg/h, respectively. On the other hand, 0.25% of GZ
      administered (5.0 mg) was eliminated into bile by 12 h, and the bile clearance
      rate (1.13 ml/h) of GZ after the subcutaneous administration of the microspheres
      was the same as that (1.13 ml/h) after the administration of GZ solution. From
      the results, it is suggested that the initial controlled release (0.18 mg/h) of
      GZ from microspheres may be beneficial for the hepatic bioavailability of GZ.

PMID- 20046074
TI  - Pharmacokinetics of orally administered tacrolimus in lupus nephritis patients.
AB  - The pharmacokinetics of orally administered tacrolimus were examined in six
      female lupus nephritis patients (mean age 43 years, range 24-55 years).
      Tacrolimus (3 mg) was administered after supper, and blood tacrolimus
      concentrations were measured just prior to dosing and 1, 2, 4, 6, 8, 12 and 24 h
      after administration. The maximum blood concentration (C(max)) was observed 4-8 h
      (mean: 6.7 h) after administration. The mean C(max) and area under the tacrolimus
      concentrationti-me curve (AUC(0-24 h)) were 12.7 ng/ml and 163.1 ng x h/ml,
      respectively. Although there was a weak correlation between AUC(0-24 h) values
      and tacrolimus concentrations 2, 4, and 6 h after administration, concentrations
      at 12 h and 24 h were highly correlated with AUC(0-24 h) values, suggesting that
      the trough concentration (C(24 h)) and C(12 h) are valid markers for therapeutic
      tacrolimus monitoring. Enzyme-linked immunoabsorbent assay (ELISA) and
      microparticle enzyme immunoassay (MEIA) measurements of blood tacrolimus
      concentrations were similar. We recommend that monitoring should be carried out
      by C(12 h) in lupus nephritis outpatients.

PMID- 20046075
TI  - [Development of semisolid dosage form of clonazepam for oral cavity
      administration].
AB  - A semisolid dosage form of clonazepam (CZP), administered to the oral cavity
      between the lower gum and bottom lip with small volume of saline, was developed
      to obtain the stable dosage which can replace the injection dosage form.
      Semisolid dosage forms were prepared using a mixture of CZP/(polyethylene glycol
      1500 (PEG))/(oleic acid (OA)) at the ratios of 1/39/0, 1/37/2 and 2/36/2 (w/w),
      named CZP1-PEG, CZP1-PEG-OA and CZP2-PEG-OA, respectively, and were evaluated in
      vitro and in vivo. No crystal of CZP was observed in CZP1-PEG-OA for at least 8
      days, while CZP crystal appeared before administration for CZP2-PEG-OA. When a
      small volume of saline was added to CZP1-PEG-OA just before the oral cavity
      administration, more than 80% (w/w) was found to exist in the soluble form. Each
      semisolid dosage form (40 mg) was administered to the oral cavity in rats, and
      CZP 1 mg suspension in 0.5% (w/v) sodium carboxymethylcellulose aqueous solution
      was administered into rat stomach as a control. CZP1-PEG-OA gave the plasma
      concentrations of more than 5 ng/ml and 12 ng/ml at 30 min and 1 h after
      administration, respectively, which might be near the plasma levels effective for
      the suppression of epileptic seizures in human, while the plasma concentration
      was less than 5 ng/ml at 30 min or did not reach 10 ng/ml at 1 h for the other
      formulations. It is proposed that the semisolid dosage form CZP1-PEG-OA should be
      a possibly useful preparation for the antiepileptic or sedative medication.

PMID- 20046076
TI  - [Pharmacological assessment of ARTCEREB irrigation and perfusion solution for
      cerebrospinal surgery based on glucose incorporation activity in primary cultures
      of rat brain cells].
AB  - ARTCEREB irrigation and perfusion solution (Artcereb) is typically used as an
      artificial fluid for applications inside the skull and spinal cavity. This in
      vitro study was conducted to assess the effects of Artcereb in cultures of rat
      fetal brain cells. Cell function following exposure to Artcereb was evaluated by
      measuring (3)H-deoxy-D-glucose incorporation activity. Cell function was
      significantly reduced in primary cultures of rat fetal brain cells at 0 h and 24
      h after 1-h or 3-h exposure to normal saline as compared with Artcereb. Cell
      function was also significantly reduced at 24 h after 3-h exposure to lactated
      Ringer's solution as compared with Artcereb. Furthermore, cell function was
      significantly reduced at 24 h after 3-h exposure to a modified Artcereb
      formulation lacking either HCO(3)(-) or Mg(2+) as compared with Artcereb, while
      cell function was unaffected at 24 h after exposure to lactated Ringer's solution
      with HCO(3)(-) or normal saline with HCO(3)(-) as compared with Artcereb. These
      findings suggest the importance of the presence of HCO(3)(-) and Mg(2+) in the
      formulation of Artcereb.

PMID- 20046077
TI  - [Collecting and sharing information about dietary supplements and functional
      foods among healthcare professionals using internet-based system].
AB  - Since we do not know much about the efficacy and safety of dietary supplements
      and functional foods (DS), it is important to collect DS-related events and to
      share the information among healthcare professionals. Therefore, we aimed to
      develop an internet-based system which would allow medical doctors and
      pharmacists to report DS-related events. We conducted a questionnaire survey
      among pharmacists about their experiences and views of DS-related adverse event
      reporting. Many pharmacists did not report events because they never had any
      patient who reported an event. This might have been, in part, owing to lack of
      awareness of an occurrence, so we collected events using our internet-based
      system, which periodically offers educational DS information. After educational
      commentaries and elucidation were appended, collected cases were distributed to
      the registered members via web pages to encourage them to be more concerned about
      the safety of DS. Additionally, we constructed a simple posting system for
      members to easily report similar events, because the questionnaire survey
      revealed that lack of time and uncertainty of causal relation between an event
      and DS were sometimes reasons not to report. We obtained several DS-related
      events both via the normal data collecting form and the simple posting system,
      and subsequently confirmed reports by e-mail contact. Our interactive system
      enabled us to obtain more detailed information about posted events. In
      conclusion, this information system for DS was proved to be useful to facilitate
      reporting of DS-related events by healthcare professionals and to accumulate
      events similar to already reported cases.

PMID- 20046078
TI  - Frequent CD7 antigen loss in aggressive natural killer-cell leukemia: a useful
      diagnostic marker.
AB  - BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm
      characterized by systemic proliferation of NK cells. However, the differential
      diagnosis of NK lymphoproliferative disorders is difficult because of the absence
      of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for
      ANKL, we analyzed the clinical data and laboratory findings obtained for 20
      patients with ANKL. METHODS: From January 2000 to July 2007, 20 patients were
      diagnosed with ANKL on the basis of bone marrow studies. We retrospectively
      analyzed the clinical features and laboratory findings, including the complete
      blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic
      results. RESULTS: The subjects included 6 women and 14 men (median age, 44 yr;
      range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and
      karyotypic abnormalities were observed in 9 patients (50%). None of the
      cytogenetic abnormalities were constantly observed in all the patients. However,
      6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of
      the leukemic NK-cells was cytoplasmic CD3(+), surface CD3(-), CD16/56(+), CD2(+),
      and CD5(-). Notably, the CD7 antigen was absent in 10 patients (50%). When the
      CD7 loss was combined with cytogenetic abnormalities, clonal markers could be
      identified in 75% of the ANKL cases. CONCLUSIONS: The CD7 antigen loss was
      frequently observed in our series of ANKL patients. In conjunction with the
      cytogenetic findings, this characteristic immunophenotypic finding can serve as a
      reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic
      analysis of CD7 expression should be included in the diagnosis of NK cell
      neoplasms.

PMID- 20046079
TI  - [Usefulness of silica clotting time for detection of lupus anticoagulants].
AB  - BACKGROUND: The presence of lupus anticoagulants (LA) is a strong risk factor for
      thrombosis in antiphospholipid syndrome. We investigated the usefulness of
      addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper
      venom test (dRVVT) for detection of LA. Also, we analyzed differences in the
      thrombotic features and the characteristics of antiphospholipid antibodies
      between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti
      cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT
      and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti
      beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using
      commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of
      the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT
      alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%)
      was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting
      thrombosis was higher in the combined test than in dRVVT or SCT alone. When
      normalized LA ratio of the two tests was compared, the group of patients with
      higher ratio of SCT showed significantly higher prevalence of recurrent abortion
      and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than
      the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can
      improve the detection sensitivity of thrombosis in LA test. And the high
      normalized LA ratio of SCT may be a useful parameter for detection of recurrent
      abortion.

PMID- 20046080
TI  - [Evaluation of platelet indices for differential diagnosis of thrombocytosis by
      ADVIA 120].
AB  - BACKGROUND: For the diagnosis of essential thrombocythemia (ET), no single
      clinical or laboratory finding of diagnostic value is available and a
      differential diagnosis of other myeloproliferative neoplasms or reactive
      thrombocytosis (RT) is needed. Following recent developments in automated blood
      cell analyzers, various platelet indices can now be measured. In this study, we
      analyzed whether platelet counts and 6 platelet indices can be used for the
      differentiation of ET from RT in patients with a platelet count of
      600x10(3)/microL or more. METHODS: The subjects studied were 31 patients with ET
      and 224 patients with RT. The platelet counts, mean platelet volume (MPV),
      plateletcrit (PCT), platelet distribution width (PDW), mean platelet mass (MPM),
      mean platelet component concentration (MPC) and large platelets (LPLT) were
      measured by ADVIA 120 (Bayer Diagnostics, USA). The mean values of each item were
      compared between the two patient groups and the sensitivity and specificity of
      each item in the diagnosis of ET were determined by ROC curve analysis. RESULTS:
      In essential thrombocythemia, all parameters except MPC were significantly higher
      than in reactive thrombocytosis. For the diagnosis of ET, the sensitivity and
      specificity were: 74.2% and 84.4%, when the platelet count was > or = 820 x
      10(3)/microL; 80.6% and 80.0%, when the plateletcrit was > or = 0.63%; and 64.5%
      and 99.1%, respectively, when LPLT was > or = 23 x 10(3)/microL. CONCLUSIONS: The
      platelet counts and platelet indices are useful for the differential diagnosis of
      thrombocytosis. The plateletcrit and LPLT are particularly useful for the
      diagnosis of ET when the platelet count is markedly increased.

PMID- 20046081
TI  - [Near-tetraploidy acute myeloid leukemia with RUNX1-RUNX1T1 rearrangement due to
      cryptic t(8;21)].
AB  - Tetraploidy or near-tetraploidy is a rare cytogenetic abnormality found in AML,
      and is divided into primary and secondary forms. The secondary tetraploidy or
      near-tetraploidy found in AML is known to be specifically associated with
      t(8;21). In this case report, FISH analysis detected RUNX1-RUNX1T1 gene
      rearrangement in the absence of cytogenetic abnormality of t(8;21), which
      suggests the presence of unvailed t(8;21). This is the first case report of
      tetraploidy or near-tetraploidy AML with cryptic RUNX1/RUNX1T1 in Korea. Although
      the prognosis of tetraploidy or near- tetraploidy with t(8;21) is known to be
      poor, this patient shows a relatively good clinical course compared to other
      reported cases.

PMID- 20046082
TI  - Determination of plasma warfarin concentrations in Korean patients and its
      potential for clinical application.
AB  - BACKGROUND: Warfarin is a widely used oral anticoagulant with broad within- and
      between-individual dose requirements. Warfarin concentrations can be monitored by
      assessing its pharmacologic effects on International Normalized Ratio (INR).
      However, this approach has not been applied in the routine clinical management of
      patients receiving warfarin therapy. We performed a plasma warfarin assay using
      high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) to
      determine if such an assay can be utilized in routine clinical practice. METHODS:
      We included a total of 105 patients with atrial fibrillation, and who were
      receiving warfarin for more than 1 yr. The plasma concentrations of total
      warfarin and 7-hydroxywarfarin were determined by HPLC-MS/MS (Waters, UK). We
      assessed the association between warfarin dose, concentration, and INR as well as
      the effects of these factors on warfarin concentrations. RESULTS: The mean
      maintenance dose of warfarin in 105 patients was 4.1 +/-1.3 mg/day (range, 1.7
      8.0 mg/day) and their mean plasma warfarin concentration was 1.3+/-0.5 mg/L. We
      defined a concentration range of 0.6-2.6 mg/L (corresponding to the 2.5th to
      97.5th percentile range of the Plasma warfarin levels in the 74 patients showing
      INR within target range) as the therapeutic range for warfarin. The correlation
      of warfarin dose with warfarin concentration (r(2)=0.259, P<0.001) was higher
      than that with INR (r(2)=0.029, P=0.072). CONCLUSIONS: There was a significant
      correlation between warfarin dose and plasma warfarin concentrations in Korean
      patients with atrial fibrillation. Hence, plasma warfarin monitoring can help
      determine dose adjustments and improve our understanding of individual patient
      response to warfarin treatment.

PMID- 20046083
TI  - [Effectiveness of sodium fluoride as a glycolysis inhibitor on blood glucose
      measurement: comparison of blood glucose using specimens from the Korea National
      Health and Nutrition Examination survey].
AB  - BACKGROUND: Accurate measurement of blood glucose concentrations is essential for
      defining diabetes, and the minimization of ex vivo glycolysis has been
      recommended. Recent guidelines advocate two kinds of methods for sample
      collection and processing: either the sodium fluoride (NaF) method or immediate
      refrigeration using a serum separation tube (SST). We investigated the difference
      between the two methods in measuring subsequent glucose concentrations using
      blood specimens from participants recruited for the fourth Korean National Health
      and Nutrition Examination Survey. METHODS: Paired venous blood samples were
      collected in an SST and a NaF tube from 1,103 men and women. SST serum was
      separated within 30 min, including standing for 15 min, and then refrigerated.
      The NaF samples were refrigerated, but not separated until immediately before
      analysis. We compared the blood glucose concentrations between the SST (SST
      glucose) and NaF (NaF glucose) methods. RESULTS: The mean SST glucose was
      significantly higher than NaF glucose (99.0 mg/dL vs 96.5 mg/dL, P<0.05). NaF
      glucose showed a negative mean bias of 2.6 mg/dL vs SST glucose but showed high
      correlation (R=0.9899). There was no significant correlation between the bias of
      blood glucose concentrations by two methods and the storage time of NaF glucose.
      CONCLUSIONS: The negative bias associated with the use of NaF tubes may
      significantly affect the prevalence of diabetes. Serum separation and
      refrigeration within 30 min after venous sampling is recommended over NaF method,
      not only to minimize the preanalytical impact on detecting diabetes but also to
      reduce sample volume and number of tubes.

PMID- 20046084
TI  - [Comparison of diagnostic utility between procalcitonin and C-reactive protein
      for the patients with blood culture-positive sepsis].
AB  - BACKGROUND: Procalcitonin (PCT) is a relatively new marker for bacterial
      infections, and its diagnostic utility has been variable across the studies. We
      investigated the diagnostic utility of PCT for the patients with blood culture
      positive sepsis, and compared it with that of C-reactive protein (CRP). METHODS:
      In 1,270 consecutive blood samples, PCT and CRP were simultaneously measured and
      results were compared according to the five categories of PCT concentrations
      (<0.05 ng/mL; 0.05-0.49 ng/mL; 0.5-1.99 ng/mL; 2-9.99 ng/mL; > or = 10 ng/mL). In
      506 samples, they were further analyzed according to the result of blood culture.
      PCT and CRP were measured using enzyme-linked fluorescent assay (bioMerieux Co.,
      France) and rate nephelometry (Beckman Coulter Co., USA), respectively. Their
      diagnostic utilities were compared using ROC curves. RESULTS: The mean
      concentrations of CRP in five categories of PCT were 15.4 mg/L, 42.1 mg/L, 101.2
      mg/L, 125.0 mg/L, 167.1 mg/L, respectively (P<0.0001). Both PCT and CRP showed
      significant differences between the two positive and negative groups of blood
      culture (PCT, 8.47 vs 2.44 ng/mL, P=0.0133; CRP, 110.48 vs 59.78 mg/L, P<0.0001).
      The areas under the ROC curves (95% confidence interval) for PCT and CRP were
      0.720 (0.644-0.788) and 0.558 (0.478-0.636), respectively, and showed a
      significant difference (P=0.005). CONCLUSIONS: The diagnostic utility of PCT is
      superior to that of CRP for the patients with blood culture-positive sepsis. PCT
      seems to be reliable for sepsis diagnosis, and may provide useful information for
      the critically ill patients.

PMID- 20046085
TI  - Hemoglobin Yamagata: hemoglobin variant detected by HbA1c test.
AB  - Hemoglobin (Hb) Yamagata is a rare Hb variant, which has been reported only twice
      one case each in Japan and Korea. This variant arises from a Lys --> Asn
      substitution due to a mutation of AAA to AAC or AAT at codon 133 of the beta
      globin gene. This study reports the third case of a patient detected with Hb
      Yamagata [HBB: c.399A>T; p.Lys133Asn] and discusses the effect of this variant on
      HbA1c measurement. This variant was detected in a 70-yr-old Korean man with
      diabetes mellitus during a routine follow-up. The HbA1c concentration determined
      using Variant ll Turbo (Bio-Rad, USA) was abnormally high at 47.9%. It was
      impossible to measure the HbA1c level accurately using Variant ll Thalassemia
      Mode (Bio-Rad, USA). However, the HbA1c levels analyzed by HLC-723 G7 (Tosoh,
      Japan), Cobas Integra (Roche, Switzerland) and NycoCard (Axis-Shield, Norway)
      were 5.0%, 8.0%, and 7.9%, respectively. This study shows that Hb Yamagata
      interferes with the accurate measurement of HbA1c levels in a diabetic patient.
      Taking these findings into consideration, we think that an immunoassay or
      affinity chromatography can be used as an alternate method for measuring the
      HbA1c level in a patient with this variant. In conclusion, a patient can be
      inferred to have an Hb variant if the HbA1c concentration is abnormally high or
      low or if there is a discrepancy between the results obtained using different
      methods, and if the clinical status of the patient suggests the presence of
      abnormal Hb. Subsequently, the HbA1c values can be determined by methods based on
      different principles.

PMID- 20046086
TI  - Characteristics of aac(6')-Ib-cr gene in extended-spectrum beta-lactamase
      producing Escherichia coli and Klebsiella pneumoniae isolated from Chungnam area.
AB  - BACKGROUND: Concomitant quinolone resistance in extended-spectrum beta-lactamase
      (ESBL)-producing Enterobacteriaceae is a crucial problem in the clinical
      management of infections. In foreign countries, the fluoroquinolone acetylating
      aminoglycoside-(6)-N-acetyltransferase (aac[6']-Ib-cr) gene, a novel plasmid
      mediated quinolone resistance determinant has been reported to occur in
      conjunction with qnr. We aim to investigate the prevalence and characteristics of
      concomitant aac(6')-Ib-cr and qnr expression in ESBL-producing Escherichia coli
      and Klebsiella pneumoniae in Korea. METHODS: Between December 2007 and April
      2008, we collected 60 and 69 clonally unrelated non-repetitive clinical isolates
      of ESBL-producing E. coli and K. pneumoniae, respectively. We studied the
      expressions of 11 types of ESBL-encoding genes, 4 types of 16s rRNA methylase
      genes; rmtA, rmtB, rmtC and armA, 3 types of qnr genes; qnrA, qnrB, qnrS and
      aac(6')-Ib. The presence of aac(6')-Ib-cr variants was detected by sequencing.
      The involvement of integrons was studied using multiplex PCR and sequencing of
      gene-cassette arrays. Conjugation experiments were performed to confirm plasmid
      mediated resistance and the relationships among co-harbored genes. RESULTS: We
      observed a high prevalence of the cr variant (61.1%) of aac(6')-Ib, and the
      prevalence of this variant in qnr and aac(6')-Ib-co-harboring isolates (67.4%)
      was higher than in qnr-negative isolates (51.7%). The high prevalence of the cr
      variant was significantly related to the high minimum inhibitory concentrations
      (MICs) of ciprofloxacin, tobramycin, and amikacin and indicated the statistically
      significant roles of qnrB, qnrS, rmtA, and rmtB in quinolone and aminoglycoside
      resistance. CONCLUSIONS: The aac(6')-Ib-cr variants were widespread and showed
      significant relation to the high-level quinolone and aminoglycoside resistance in
      ESBL-producing E. coli and K. pneumoniae.

PMID- 20046087
TI  - [Hepatitis A virus seropositivity among healthcare workers at a university
      hospital in Korea].
AB  - BACKGROUND: Healthcare workers (HCW) are known as a risk group of hepatitis A
      virus (HAV) infection and vaccination of this group against HAV has been
      suggested. However, the seroprevalence of HAV antibody among HCW in Korea has not
      been reported. We investigated the seropositivity of HAV antibody in HCW, to
      obtain a baseline data. METHODS: We measured serum total HAV antibody using
      chemiluminescent immunoassay (ADVIA Centaur, Germany) in 174 HCW at one
      university hospital in Seoul, Korea. RESULTS: Serum HAV antibody was positive in
      48 (27.6%) of 174 subjects tested. The seropositivity of HAV antibody was
      significantly increased with increasing age: 21.1% (26/123), 55% (22/40), and
      100% (11/11) in the age groups of 20's, 30's, and 40's, respectively (P<0.001).
      However it was not significantly different among different occupations
      (physicians 38%, nurses 24.6%, other workers 31.4%, P=0.376) and work places
      (medical ward 29.1%, pediatric ward 25.9%, emergency room 34.4%, laboratory 0%,
      P=0.140). The seroprevalence rate of HAV antibody in the age groups of 20's and
      30's in this study was not higher than that of previous studies on non-HCW
      populations in Korea since 2006. CONCLUSIONS: The seroprevalence of HAV antibody
      among HCW in the age groups of 20's and 30's in a Korean hospital was not higher
      than that of non-HCW populations, and the seropositivity increased with
      increasing age. Further studies are needed for the age-specific strategy for
      vaccination, considering the increased risk of exposure in HCW to HAV infection
      in hospital environment with the increase of symptomatic patients with HAV.

PMID- 20046088
TI  - Serologic screening of pregnant Korean women for primary human cytomegalovirus
      infection using IgG avidity test.
AB  - BACKGROUND: Primary human cytomegalovirus (CMV) infection during pregnancy is a
      major cause of congenital malformation. We detected primary CMV infection in
      pregnant Korean women by using an algorithm that comprises CMV IgG, IgM, and IgG
      avidity tests. METHODS: During a 2-month period, 744 pregnant women who were at
      10-19 weeks of gestation were consecutively enrolled in this study. Human anti
      CMV IgG and IgM levels in their sera were determined by chemiluminescence
      immunoassays. Serum samples from the women who were positive for CMV IgG and IgM
      were assayed by the ARCHITECT CMV IgG avidity test in order to distinguish
      primary from non-primary CMV infection. Gross examination of the neonates of the
      women who were positive for CMV IgM was conducted. RESULTS: The seroprevalence of
      CMV IgG and IgM was estimated to be 98.1% and 1.7%, respectively. The samples
      from all the women who were positive for CMV IgM or with grey zone results
      contained high avidity CMV IgG. Seven women with positive CMV IgG and IgM results
      who completed follow-up up to delivery showed no gross evidence of in utero CMV
      transmission. CONCLUSIONS: Maternal primary CMV infection was not detected in any
      of the pregnant women included in this study cohort. CMV IgG avidity test enabled
      the identification of women who were at a low risk of transmitting CMV infection
      and provided informative for subsequent pregnancy outcomes. Compared to previous
      studies, the seroprevalence of CMV IgG antibody across pregnant Korean women
      remained unchanged.

PMID- 20046089
TI  - [An epidemiological analysis of hepatitis A virus serologic markers during the
      recent four years in Korea].
AB  - BACKGROUND: To establish effective preventive measures for hepatitis A virus
      (HAV) infection, a nationwide epidemiologic study on seroprevalence of anti-HAV
      and the disease prevalence is needed. The aim of this study was to analyze the
      recent sero-epidemiological changes of hepatitis A markers in Korea. METHODS: The
      results of 11,068 anti-HAV total and 32,360 anti-HAV IgM tests by electro
      chemiluminescence immunoassay (ECLIA) that had been requested in recent four
      years (2005-2008) to a reference medical laboratory from 1,699 institutions
      nationwide were retrospectively analyzed according to the distribution of year,
      sex, and age groups. RESULTS: The overall positive rate of anti-HAV total was
      62.8%. The overall positive rate of anti-HAV IgM was 11.0%, showing a
      significantly increasing trend by year: 7.7%, 10.9%, 8.9%, and 14.3% in 2005,
      2006, 2007, and 2008, respectively (P<0.0001). The positive rate of anti-HAV IgM
      was higher in male than in female subjects (11.8% vs 10.0%, P<0.0001), and 81.8%
      (2,916/3,566) of the anti-HAV IgM positive results were observed in the age
      groups of 21-40 yr. The annual positive rates of anti-HAV total and anti-HAV IgM
      showed significantly decreasing and increasing trends, respectively, in the age
      groups of > or = 21 yr. CONCLUSION: In accordance with a decreasing sero
      positivity of anti-HAV total, the prevalence of acute hepatitis A virus infection
      has been considerably increased during the recent four years in the age groups of
      > or = 21 yr. The results of this study could be used effectively as a basic data
      for establishing effective preventive measures for hepatitis A including
      vaccination in these susceptible age groups.

PMID- 20046090
TI  - [Perception of the risks of blood transfusion in Koreans].
AB  - BACKGROUND: The perceived risks of blood transfusions are important to be
      considered in creating a blood service policy. We surveyed the perception of
      blood transfusion risks among Korean laypeople. METHODS: A one-month nationwide
      telephone survey was conducted in September, 2007. The questionnaire was designed
      to assess the demographics of respondents, their responses to the term 'blood
      transfusion', and the perceived risks of a transfusion. A total of 500 interviews
      were completed. RESULTS: The words evoked by the term 'blood transfusion'
      included blood, donation, AIDS, help, and patients. About one third (33.6-35.8%)
      of the respondents gave a moderate to high rating for the perceived risks of
      blood transfusions. More than half (55.6%) of the respondents agreed that the
      blood supply in Korea is safe, and 81.6% of the respondents agreed to be
      transfused when transfusion is needed. The perceived risk of a blood transfusion
      was greater in women than in men and in people who never had a transfusion than
      those who had. More men than women agreed that the blood supply in Korea is safe,
      and the proportion of respondents who agreed to be transfused when needed was
      higher in men and in less educated people. The relative perceived transfusion
      risk (scale of 10) was 4.5+/-2.3. CONCLUSIONS: The Koreans in the survey had a
      tendency of positive thinking about blood transfusions, and previous transfusion
      experiences appear to decrease the fear about transfusions. These results will be
      useful in understanding how Koreans think about the risks associated with
      transfusions.

PMID- 20046091
TI  - A case of immune hemolytic anemia induced by ceftizoxime and cefobactam
      (sulbactam/cefoperazone).
AB  - Simultaneous drug-induced immune hemolytic anemia (DIIHA) caused by multiple
      drugs is rare. We report a case of a patient who developed DIIHA caused by 2
      drugs. The patient's serum exhibited agglutination of ceftizoxime- or sulbactam
      coated red blood cells (RBCs; via a drug-adsorption mechanism) and of uncoated
      RBCs in the presence of sulbactam (via an immune-complex mechanism). Although
      ceftizoxime is known to exhibit a positive reaction by an immune-complex method
      with or without reactivity with drug-coated RBCs, this patient's antibodies were
      reactive only against drug-coated RBCs. On the other hand, sulbactam, which is
      known to cause hemolytic anemia by nonimmunologic protein adsorption, exhibited
      positive reactions in tests with both drug-coated RBCs and in the presence of
      sulbactam. This is the first report of DIIHA due to a sulbactam-cefoperazone
      combination and the fourth report of DIIHA due to ceftizoxime. Owing to the
      patient's complicated laboratory results, DIIHA was suspected only at a late
      stage. We propose that for the prompt diagnosis of DIIHA, tests for all possible
      causative drugs should be conducted by 2 methods.

PMID- 20046092
TI  - [An experience of ABO-incompatible kidney transplantation using plasmapheresis
      and anti-CD20 monoclonal antibody].
AB  - Due to an extreme shortage of cadaveric kidneys, many centers in Japan
      successfully performed ABO-incompatible kidney transplantations using
      plasmapheresis, splenectomy and immunosuppression. Recently, a protocol including
      anti-CD20 monoclonal antibody (rituximab) and antigen-selective immunoadsorption
      has been used for ABO-incompatible transplantation in Europe. In Korea, ABO
      incompatible kidney transplantation has been rarely performed. We report an
      experience of successful ABO-incompatible kidney transplantation using
      plasmapheresis and rituximab. The patient was a 32-yr-old female suffering from
      chronic renal failure, and her blood type was O, Rh+. The donor was her husband,
      and his blood type was B, Rh+. A combination therapy including 5 times of
      plasmapheresis starting from 10 days before transplantation with 2-day interval,
      intravenous gammaglobulin, rituximab at 2 weeks before transplantation and potent
      immunosuppression successfully decreased the titers of anti-A and anti-B
      antibodies to 1:2 and 1:1, respectively. The kidney transplantation was
      successful without any sign of hyperacute or acute rejection.

PMID- 20046093
TI  - Evaluation of two commercial HLA-B27 real-time PCR kits.
AB  - BACKGROUND: The standard PCR with sequence-specific primers (SSP) is a widely
      used method of HLA-B27 typing in clinical practice. The aim of our study was to
      evaluate 2 Korean HLA-B27 kits with different real-time PCR chemistries. METHODS:
      To validate the accuracy of real-time PCR kits, we selected 28 HLA-B27-positive
      samples and 33 HLA-B27-negative samples with a wide range of different HLA-B
      specificities typed by standard PCR-SSP. The 2 real-time PCR kits used were the
      AccuPower HLA-B27 real-time PCR kit (Bioneer, Korea) with TaqMan probes and the
      Real-Q HLA-B*27 detection kit (BioSewoom, Korea) with SYBR Green I dye for
      melting curve analysis. RESULTS: All 61 samples typed by PCR-SSP demonstrated a
      perfect concordance with the 2 real-time PCR assays. It was possible to clearly
      discriminate between HLA-B27-positive and -negative samples in both real-time
      assays. CONCLUSIONS: In summary, both real-time PCR assays for HLA-B27 were fast,
      reliable, well-adapted for routine laboratory testing, and attractive
      alternatives to the conventional PCR-SSP method.

PMID- 20046094
TI  - [Application of a diagnostic method using reverse transcription-PCR ELISA for the
      diagnosis of enteroviral infections].
AB  - BACKGROUND: Enteroviruses are known as major pathogen for aseptic meningitis.
      Although rapid diagnosis for enteroviruses is very essential to exclude bacterial
      infections in patients with meningitis, classical diagnostic method based on
      virus isolation is not practicable for timely treatment of patients due to its
      laborious and time-consuming procedure. Recently molecular methodologies as
      alternatives are routinely used for rapid and sensitive diagnosis for
      enteroviruses infections. METHODS: Reverse transcription (RT)-PCR ELISA kit for
      targeting 5' non-coding region (NCR) with highly conserved genetic identity among
      all genotypes of enteroviruses was introduced in this investigation. RT-PCR ELISA
      was evaluated about sensitivity and specificity through virus isolation using
      clinical specimens from patients suspected of enteroviral infections and
      enteroviral isolates comparing with conventional RT-PCR identifying them.
      RESULTS: The detection limit of the RT-PCR ELISA was up to 10-100 folds higher
      than virus isolation using cell culture and conventional RT-PCR. On comparison
      between above two methods, the detection rate of RT-PCR ELISA for clinical
      specimens from patients with aseptic meningitis was 7% higher than that of
      conventional RT-PCR targeting 5'NCR (P=0.016). CONCLUSIONS: Our results suggest
      that RT-PCR ELISA developed in this study could be an alternative diagnostic
      method for the detection of enteroviral genome with high sensitivity and
      specificity.

PMID- 20046095
TI  - Kin recognition: another biological function for root secretions.
AB  - In the past, studies have shown that plants do indeed have the ability to
      recognize other plants in their surroundings based on relatedness and identity.
      Although, mechanisms for these recognitions have been proposed, to date, one has
      not been supported. In our recent work, we showed that Arabidopsis plants
      distinguish self/non self or kin/stranger plants through secretion and by
      recognition of root secretions. Additionally, we show that this kin response can
      be eliminated through treatment with a root secretion inhibitor and that the kin
      recognition response is robust through several Arabidopsis accessions. We hope
      that this study can promote the understanding of root secretion and its numerous
      roles in rhizosphere communications.

PMID- 20046096
TI  - The EphB2 tumor suppressor induces autophagic cell death via concomitant
      activation of the ERK1/2 and PI3K pathways.
AB  - EphB2 is a tyrosine kinase receptor that has been shown to be a tumor suppressor
      gene in various cancers. However the mechanisms of this function are unknown. We
      report that EphB2 induces a form of cell death that does not involve the
      formation of apoptotic bodies or nuclear fragmentation and is instead accompanied
      by extensive vacuolization. Transmission electron microscopy demonstrates
      cytoplasmic vacuoles in EphB2-overexpressing cells that resembled autophagosomes.
      Using an EYFP-LC3 fusion protein and immunoblotting, we detected LC3 aggregation
      and conversion from form I to form II, both hallmarks of autophagy, in EphB2
      transfected cells. Silencing of the autophagy regulating genes ATG5 or ATG7 using
      shRNAs, strongly prevented EphB2-induced cell death, further confirming its
      autophagic nature. EphB2 expression results in mitochondrial depolarization and
      translocation of cytochrome c from the mitochondria to the cytosol. Mapping of
      signaling pathways revealed novel information about the mechanisms of action of
      EphB2. We demonstrated that the MAPK pathway is important in the pro-death action
      of EphB2, through ERK1/2 phosphorylation and inhibition of this pathway using
      PD98059 counters EphB2-driven cell death. In addition, we found that inhibition
      of class III PI3K pathway, using the autophagy inhibitor 3MA, but not class I
      PI3K inhibition using LY294002, also effectively blocks EphB2- induced cell
      death. Finally, EphB2 expression inactivates Akt, which is a known inhibitor of
      autophagy. In conclusion, the EphB2 receptor induces an autophagic cell death
      that is mediated through the ERK1/2 and PI3K/Akt pathways.

PMID- 20046097
TI  - miR-449 regulates CDK-Rb-E2F1 through an auto-regulatory feedback circuit.

PMID- 20046098
TI  - Uncovering a tumor-suppressor function for Drosophila polycomb group genes.

PMID- 20046099
TI  - Cell cycle-dependent phosphorylation of Rad53 kinase by Cdc5 and Cdc28 modulates
      checkpoint adaptation.
AB  - In budding yeast the evolutionarily conserved checkpoint response varies in its
      sensitivity to DNA damaging agents through the cell cycle. Specifically, higher
      amounts of damage are needed to activate the downstream checkpoint kinase Rad53
      in S-phase cells. We examined here whether phosphorylation of Rad53 itself by
      cell cycle-dedicated kinases regulates Rad53 activation. We found that during
      unperturbed growth Rad53 exhibits a small phosphorylation-dependent
      electrophoretic mobility shift in G(2), M and G(1) phases of the cell cycle that
      is lost in S phase. We show that Rad53 is phosphorylated in vitro by Cdc5, a
      mitotic Polo-like kinase, and by the yeast cyclin-dependent kinase, Cdc28.
      Consistently, the cell cycle-dependent Rad53 mobility shift requires both Cdc5
      and Cdc28 activities. We mapped the in vitro targeted phosphorylation sites by
      mass spectrometry and confirmed with mass spectroscopy that serines 774, 789 and
      791 within Rad53 are phosphorylated in vivo in M-phase arrested cells. By
      creating nonphosphorylatable mutations in the endogenous RAD53 gene, we confirmed
      that the CDK and Polo kinase target sites are responsible for the observed cell
      cycle-dependent shift in protein mobility. The loss of phospho-acceptor sites
      does not interfere with Rad53 activation but accelerates checkpoint adaptation
      after induction of a single irreparable double-strand break. We thus demonstrate
      that cell cycle-dependent phosphorylation can fine-tune the response of Rad53 to
      DNA damage.

PMID- 20046100
TI  - The complexity of phosphorylated H2AX foci formation and DNA repair assembly at
      DNA double-strand breaks.
AB  - The maintenance of genome stability requires efficient DNA double-stranded break
      (DSB) repair mediated by the phosphorylation of multiple histone H2AX molecules
      near the break sites. The phosphorylated H2AX (gammaH2AX) molecules form foci
      covering many megabases of chromatin. The formation of gamma-H2AX foci is
      critical for efficient DNA damage response (DDR) and for the maintenance of
      genome stability, however, the mechanisms of protein organization in foci is
      largely unknown. To investigate the nature of gammaH2AX foci formation, we
      analyzed the distribution of gammaH2AX and other DDR proteins at DSB sites using
      a variety of techniques to visualize, expand and partially disrupt chromatin. We
      report here that gammaH2AX foci change composition during the cell cycle, with
      proteins 53BP1, NBS1 and MRE11 dissociating from foci in G(2) and mitosis to
      return at the beginning of the following G(1). In contrast, MDC1 remained
      colocalized with gamma-H2AX during mitosis. In addition, while gammaH2AX was
      found to span large domains flanking DSB sites, 53BP1 and NBS1 were more
      localized and MDC1 colocalized in doublets in foci. H2AX and MDC1 were found to
      be involved in chromatin relaxation after DSB formation. Our data demonstrates
      that the DSB repair focus is a heterogeneous and dynamic structure containing
      internal complexity.

PMID- 20046101
TI  - [Surgical site infections in Italy].
AB  - Surgical site infections (SSIs) are recognized as a common surgical complication,
      occurring in about 2-5% of all surgical procedures. SSIs represent the third most
      frequent nosocomial infection, accounting for 14.6% of all infections observed in
      hospitalised patients and 38% of those observed among surgical patients.
      Strategies for the prevention of SSIs also include surveillance which has proved
      very effective. The most recent surveillance study carried out at a national
      level in Italy is Kir-Nos, a multicentric study sponsored by GlaxoSmithKline and
      performed between April and June 2002 in 32 different General Surgery Units for a
      total of 2972 surgical patients enrolled. Results emerging from the study clearly
      indicate that many patients receive inappropriate antimicrobial prophylaxis,
      especially in terms of drug choice, route and timing of administration. Given the
      high economic burden that infections provoke, beyond the increased morbidity and
      mortality, it appears mandatory to improve our tools in order to reduce their
      incidence, as a reduction of only 0.1% can result in a considerable saving of
      economic resources to be allocated to other activities, such as screening and
      prevention programs.

PMID- 20046102
TI  - An active microbiological surveillance project at an Italian teaching hospital:
      microbial isolates, recent epidemiological trends, major clinical concerns, and
      antimicrobial susceptibility rates during a four-year period.
AB  - A microbiological surveillance program is currently performed at our tertiary
      care teaching hospital. The temporal trend of microbial isolates from patients
      admitted during four calendar years (2004 to 2007) was analyzed according to the
      main bacterial and fungal culture organisms. The same pathogens isolated more
      than once from the same patient within one month were considered only once. On
      the whole, the main pathogen group remained that of Enterobacteriaceae (6,608
      isolations out of 19,666: 33.6%, with Escherichia coli found in 60-75% of cases),
      with no significant difference over time. Staphylococci (4,150 isolates), and
      enterococci (3,276 isolates) were the two largest groups after
      Enterobacteriaceae, but staphylococci significantly declined during the four-year
      period (p .001), mainly due to progressively reduced isolation of coagulase
      negative staphylococci. By contrast, a slight increase in enterococci occurred (p
      .05). Based on the frequency of isolation, Gram-negative oxidase-positive
      organisms accounted for 2,109 episodes, followed by other aerobic Gram-positive
      organisms other than Staphylococci-Enterococci (613 isolates), and anaerobes (583
      isolates): no significant variations occurred over time for these last microbial
      groups. With regard to Gram-negative oxidase-negative microorganisms (567
      isolates), non-beta-haemolytic streptococci (464 cases) and beta-haemolytic
      streptococci (260 isolates), a significant reduction of frequency occurred from
      2004 to 2007 (p.05 to p.001). Finally, fungal infections accounted for 1,036
      overall episodes, in over 80% of cases represented by Candida spp. Prospective
      microbiological monitoring is expected to contribute significantly to our
      knowledge of local epidemiological figures and antimicrobial sensitivity profile
      of hospital infections, and plays a major role in selecting both treatment and
      chemoprophylaxis schedules, especially on a local-regional basis. Although the
      major causative agents of in-patient infections remain Enterobacteriaceae, a
      significant decline in coagulase-negative Staphylococci, all Streptococci, and
      Gram-negative oxidase-negative organisms occurred over the four-year period,
      while Enterococci showed a mild increase over time.

PMID- 20046103
TI  - Efficacy and safety of a salvage regimen based on tipranavir, enfuvirtide and
      three nucleoside analogues in HIV1 infected patients with clinical progression:
      96-week evaluation.
AB  - In recent years, novel antiretroviral drugs have become available for multi
      experienced HIV-infected patients with limited options. We enrolled seven
      advanced HIV-patients, failing multiple previous HAART regimens, in virological
      failure on their current HAART regimen and showing recent clinical and
      immunological progression. All patients were prescribed a double-boosted
      tipranavir plus enfuvirtide based regimen, in addition to zidovudine, tenofovir
      and lamivudine for salvage therapy. To assess susceptibility to tipranavir, the
      tipranavir genotypic resistance score was calculated and two years later this was
      re-evaluated on an updated tipranavir genotypic score algorithm. At baseline, CD4
      were 139/mcL (more or less 145), HIV-1 RNA was 822,700 cp/mL. All patients
      achieved HIV-1 RNA levels less than 400 cp/mL between 12 weeks and 24 weeks of
      observation; two reached less than 50 cp/mL during this period. At 48 weeks three
      patients had reached less than 50 cp/mL; three other patients had HIV RNA less
      than 200 cp/mL. At 72 and 96 weeks HIV viraemia was less than 50 cp/mL in six
      patients; CD4 T-cell counts 285/mcL (more o less 198). No AIDS-defining events
      were recorded. Adverse events did not need to stop or change HAART. Strong 3 NRTI
      backbone could help efficacy and durability, and frequent evaluations in complex
      patients can help to manage toxicity.

PMID- 20046104
TI  - In vitro activity of tigecycline against multidrug-resistant Acinetobacter
      baumannii clinical isolates.
AB  - This survey was conducted to evaluate the in vitro activity of tigecycline
      against 50 isolates of multidrug-resistant (MDR) Acinetobacter baumannii.
      Isolates of A. baumannii were resistant to ciprofloxacin, chloramphenicol,
      imipenem, levofloxacin, piperacillin and piperacillin-tazobactam, but were always
      susceptible to colistin. MICs of tigecycline were determined by E-test in Mueller
      Hinton agar. The results of the study showed that 50% of the A. baumannii strains
      were susceptible to tigecycline.

PMID- 20046105
TI  - Antibiotic regimen including linezolid for treating prosthetic valve endocarditis
      with cerebral embolism due to methicillin-susceptible Staphylococcus aureus after
      failure with oxacillin and teicoplanin.
AB  - A case of prosthetic valve endocarditis due to methicillin susceptible
      Staphylococcus aureus (MSSA) with cerebral metastatic seeding is described. The
      patient is a 61 year old man with diabetes mellitus, chronic renal failure and
      previous bacterial endocarditis. Despite appropriate MSSA therapy, the patient
      was eventually cured with the introduction of linezolid, without needing surgical
      intervention.

PMID- 20046106
TI  - [A case of community-acquired MRSA (CA-MRSA) sepsis complicated by
      meningoencephalitis and cerebral abscess, successfully treated with linezolid].
AB  - The authors describe a clinical case regarding a young female patient affected by
      sepsis due to methicillin-resistant Staphylococcus aureus (MRSA), associated to
      meningoencephalitis and cerebral abscess. The patient had no contact with
      hospitals in the months prior to illness and had always been healthy. She
      recovered thanks to linezolid therapy. The MRSA strain proved positive for Panton
      Valentine leukocidin (PVL positive) and was therefore defined as community
      acquired MRSA (CA-MRSA).

PMID- 20046107
TI  - Squamous cell carcinoma arising from long-term (50-year) Lupus vulgaris: is there
      a need for a close medical follow-up in such chronic diseases?
AB  - Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are
      represented by miliary tuberculosis of the skin, tuberculous chancre,
      scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and
      lupus vulgaris (LV). Among this group, LV is the most common skin condition,
      diagnosed in 10% of tuberculotic patients. The authors report herein a case of
      squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and
      underline the need of an extensive follow-up of tuberculotic lesions.

PMID- 20046108
TI  - Infant botulism mimicking an acute abdomen.
AB  - Botulism is the acute, flaccid paralysis caused by a neurotoxin produced by
      Clostridium botulinum. In the infant, clinical symptoms are usually unspecific
      such as poor feeding, weak suck, feeble cry, drooling, followed by a symmetric,
      descending, flaccid paralysis beginning with the cranial nerve musculature. The
      initial symptoms of the disease are often similar to several diseases and
      therefore differential diagnosis is very difficult and rarely suspected by the
      physician. Since 2004 only 22 cases of infant botulism have been reported in
      Italy. Since most paediatricians are unfamiliar with the clinical manifestations
      of infant botulism, the diagnosis can be easily missed. Hence the disease may
      well be underestimated and underreported. We report a clinical case of botulism
      presenting initially with abdominal distention, thereby mimicking acute abdomen.

PMID- 20046109
TI  - Community-acquired streptococcal toxic shock syndrome.

PMID- 20046110
TI  - First enteric Escherichia fergusonii from Italy.

PMID- 20046111
TI  - [The Antonine Plague and the decline of the Roman Empire].
AB  - The Antonine Plague, which flared up during the reign of Marcus Aurelius from 165
      AD and continued under the rule of his son Commodus, played such a major role
      that the pathocenosis in the Ancient World was changed. The spread of the
      epidemic was favoured by the occurrence of two military episodes in which Marcus
      Aurelius himself took part: the Parthian War in Mesopotamia and the wars against
      the Marcomanni in northeastern Italy, in Noricum and in Pannonia. Accounts of the
      clinical features of the epidemic are scant and disjointed, with the main source
      being Galen, who witnessed the plague. Unfortunately, the great physician
      provides us with only a brief presentation of the disease, his aim being to
      supply therapeutic approaches, thus passing over the accurate description of the
      disease symptoms. Although the reports of some clinical cases treated by Galen
      lead us to think that the Antonine plague was caused by smallpox,
      palaeopathological confirmation is lacking. Some archaeological evidence (such as
      terracotta finds) from Italy might reinforce this opinion. In these finds, some
      details can be observed, suggesting the artist's purpose to represent the classic
      smallpox pustules, typical signs of the disease. The extent of the epidemic has
      been extensively debated: the majority of authors agree that the impact of the
      plague was severe, influencing military conscription, the agricultural and urban
      economy, and depleting the coffers of the State. The Antonine plague affected
      ancient Roman traditions, also leaving a mark on artistic expression; a renewal
      of spirituality and religiousness was recorded. These events created the
      conditions for the spread of monotheistic religions, such as Mithraism and
      Christianity. This period, characterized by health, social and economic crises,
      paved the way for the entry into the Empire of neighbouring barbarian tribes and
      the recruitment of barbarian troops into the Roman army; these events
      particularly favoured the cultural and political growth of these populations. The
      Antonine Plague may well have created the conditions for the decline of the Roman
      Empire and, afterwards, for its fall in the West in the fifth century AD.

PMID- 20046112
TI  - Exploring intensive care unit-acquired weakness. Preface.

PMID- 20046113
TI  - Intensive care unit-acquired weakness: framing the topic.
AB  - One of the many potential sequelae of intensive care is prolonged weakness, which
      can be associated with increased morbidity during the intensive care unit stay
      and long-term functional disability. Despite increased awareness of this
      complication in recent years, diagnosing intensive care unit-acquired weakness
      remains difficult and there are no specific therapies. Management, therefore,
      relies on limiting its short- and long-term effects. One method by which this may
      be achieved is to reduce sedative use and promote early mobilization and
      exercise.

PMID- 20046114
TI  - A framework for diagnosing and classifying intensive care unit-acquired weakness.
AB  - Neuromuscular dysfunction is prevalent in critically ill patients, is associated
      with worse short-term outcomes, and is a determinant of long-term disability in
      intensive care unit survivors. Diagnosis is made with the help of clinical,
      electrophysiological, and morphological observations; however, the lack of a
      consistent nomenclature remains a barrier to research. We propose a simple
      framework for diagnosing and classifying neuromuscular disorders acquired in
      critical illness.

PMID- 20046115
TI  - Intensive care unit-acquired weakness: risk factors and prevention.
AB  - Intensive care unit-acquired weakness, the main clinical sign of critical illness
      neuromyopathy, is an increasingly recognized cause of prolonged mechanical
      ventilation and delayed return to physical self-sufficiency. Identifying risk
      factors and developing preventive measures are therefore important goals. Several
      studies on risk factors for critical illness neuromyopathy including prospective
      observational studies with a multivariate analysis of potential risk factors were
      conducted over the last decade. A large body of data is also available from two
      large prospective randomized trials comparing the effect of strict vs.
      conventional blood-glucose control on intensive care unit mortality and on
      secondary outcomes including the occurrence of critical illness neuromyopathy.
      Five central risk factors and their related potential measures to prevent
      intensive care unit-acquired weakness can be identified including multiple organ
      failure, muscle inactivity, hyperglycemia, and use of corticosteroids and
      neuromuscular blockers. Although strong evidence regarding the efficacy of
      preventive measures is still lacking, the results of available studies are
      promising and cast doubt on the widespread belief that the treatment of intensive
      care unit-acquired weakness is essentially supportive. Early identifying and
      treating conditions leading to multiple organ failure, especially severe sepsis
      and septic shock, avoiding unnecessary deep sedation and excessive blood glucose
      levels, promoting early mobilization, and carefully weighing the risks and
      benefits of corticosteroids might contribute to reduce the incidence and severity
      of intensive care unit-acquired weakness.

PMID- 20046116
TI  - Use of electrophysiologic testing.
AB  - OBJECTIVE: To define the electrophysiologic tests to diagnose critical illness
      myopathy and critical illness polyneuropathy in intensive care unit patients.
      DESIGN: Literature review. MEASUREMENTS AND MAIN RESULTS: Critical illness
      myopathy and neuropathy are common complications in the critically ill patient.
      Myopathy and neuropathy are equally common, and often coexist.
      Electrophysiological alterations of peripheral nerves and muscle have an early
      onset in the first days of intensive care unit stay or shortly after sepsis, and
      precede the structural alterations. Conventional electrophysiologic evaluation
      can be performed easily on most intensive care unit patients, including patients
      with altered consciousness; in conjunction with direct muscle stimulation, it can
      differentiate myopathy from neuropathy, which might be important to define the
      long-term prognosis. However, electrophysiologic tests are not universally
      available; their interpretation requires special expertise; and their application
      is time consuming. A recently proposed simplified test of peroneal nerve
      stimulation could be used as a screening method to select patients who merit in
      depth neurologic evaluation. CONCLUSIONS: Early identification of neuromuscular
      alterations by means of electrophysiologic tests may be of value for targeted
      treatments and to anticipate the risk of short-term disability. Complete
      neurologic and electrophysiological evaluation is important to define the risk of
      long-term disability after intensive care unit discharge.

PMID- 20046117
TI  - Measurement of muscle strength in the intensive care unit.
AB  - Traditional (indirect) techniques, such as electromyography and nerve conduction
      velocity measurement, do not reliably predict intensive care unit-acquired muscle
      weakness and its clinical consequences. Therefore, quantitative assessment of
      skeletal muscle force is important for diagnosis of intensive care unit-acquired
      motor dysfunction. There are a number of ways for assessing objectively muscle
      strength, which can be categorized as techniques that quantify maximum voluntary
      contraction force and those that assess evoked (stimulated) muscle force.
      Important factors that limit the repetitive evaluation of maximum voluntary
      contraction force in intensive care unit patients are learning effects, pain
      during muscular contraction, and alteration of consciousness.The selection of the
      appropriate muscle is crucial for making adequate predictions of a patient's
      outcome. The upper airway dilators are much more susceptible to a decrease in
      muscle strength than the diaphragm, and impairment of upper airway patency is a
      key mechanism of extubation failure in intensive care unit patients. Data suggest
      that the adductor pollicis muscle is an appropriate reference muscle to predict
      weakness of muscles that are typically affected by intensive care unit-acquired
      weakness, i.e., upper airway as well as extremity muscles. Stimulated (evoked)
      force of skeletal muscles, such as the adductor pollicis, can be assessed
      repetitively, independent of brain function, even in heavily sedated patients
      during high acuity of their disease.

PMID- 20046118
TI  - Sepsis-associated encephalopathy and its differential diagnosis.
AB  - Sepsis is often complicated by an acute and reversible deterioration of mental
      status, which is associated with increased mortality and is consistent with
      delirium but can also be revealed by a focal neurologic sign. Sepsis-associated
      encephalopathy is accompanied by abnormalities of electroencephalogram and
      somatosensory-evoked potentials, increased in biomarkers of brain injury (i.e.,
      neuron-specific enolase, S-100 beta-protein) and, frequently, by
      neuroradiological abnormalities, notably leukoencephalopathy. Its mechanism is
      highly complex, resulting from both inflammatory and noninflammatory processes
      that affect all brain cells and induce blood-brain barrier breakdown, dysfunction
      of intracellular metabolism, brain cell death, and brain injuries. Its diagnosis
      relies essentially on neurologic examination that can lead one to perform
      specific neurologic tests. Electroencephalography is required in the presence of
      seizure; neuroimaging in the presence of seizure, focal neurologic signs or
      suspicion of cerebral infection; and both when encephalopathy remains
      unexplained. In practice, cerebrospinal fluid analysis should be performed if
      there is any doubt of meningitis. Hepatic, uremic, or respiratory encephalopathy,
      metabolic disturbances, drug overdose, withdrawal of sedatives or opioids,
      alcohol withdrawal delirium, and Wernicke's encephalopathy are the main
      differential diagnoses of sepsis-associated encephalopathy. Patient management is
      based mainly on controlling infection, organ system failure, and metabolic
      homeostasis, at the same time avoiding neurotoxic drugs.

PMID- 20046119
TI  - Physical inactivity and muscle weakness in the critically ill.
AB  - Patients in the intensive care unit commonly develop muscle weakness. In part,
      this reflects loss of mechanical loading due to physical inactivity, bed rest, or
      immobilization. Mechanical unloading stimulates a complex adaptive response that
      results in muscle atrophy and loss of specific force. One element of this
      response is slowing of protein synthesis, which is regulated by signaling
      pathways downstream of mammalian target of rapamycin and insulin-like growth
      factor-1. In parallel, protein degradation is accelerated via three coordinate
      processes: calcium-dependent proteolysis, adenosine triphosphate-dependent
      proteolysis, and lysosomal proteolysis. Finally, unloading stimulates apoptosis
      of a subset of myonuclei within multinucleated muscle fibers. This helps to
      stabilize the relationship between nuclear number and cell volume during atrophy.
      Each of these responses is promoted by concurrent development of oxidative stress
      caused by increased production of reactive oxygen species in unloaded muscle
      fibers. Countermeasures that lessen the effects of unloading include physical
      activity, nutritional supplements, hormone therapy, and antioxidant
      administration. Targeted research is needed to define the role of mechanical
      unloading in intensive care unit-associated weakness and develop countermeasures
      to preserve muscle function, lessen illness, and hasten the recovery of
      critically ill patients.

PMID- 20046120
TI  - Prolonged mechanical ventilation alters diaphragmatic structure and function.
AB  - OBJECTIVE: To review current knowledge about the impact of prolonged mechanical
      ventilation on diaphragmatic function and biology. MEASUREMENTS: Systematic
      literature review. CONCLUSIONS: Prolonged mechanical ventilation can promote
      diaphragmatic atrophy and contractile dysfunction. As few as 18 hrs of mechanical
      ventilation results in diaphragmatic atrophy in both laboratory animals and
      humans. Prolonged mechanical ventilation is also associated with diaphragmatic
      contractile dysfunction. Studies using animal models revealed that mechanical
      ventilation-induced diaphragmatic atrophy is due to increased diaphragmatic
      protein breakdown and decreased protein synthesis. Recent investigations have
      identified calpain, caspase-3, and the ubiquitin-proteasome system as key
      proteases that contribute to mechanical ventilation-induced diaphragmatic
      proteolysis. The scientific challenge for the future is to delineate the
      mechanical ventilation-induced signaling pathways that activate these proteases
      and depress protein synthesis in the diaphragm. Future investigations that define
      the signaling mechanisms responsible for mechanical ventilation-induced
      diaphragmatic weakness will provide the knowledge required for the development of
      new medicines that can maintain diaphragmatic mass and function during prolonged
      mechanical ventilation.

PMID- 20046122
TI  - Skeletal muscle aging: role of reactive oxygen species.
AB  - During aging, a significant loss of skeletal muscle mass and function occurs that
      can have a dramatic impact on the quality of life of older individuals. The
      processes underlying this loss of mass and function are unknown, but a chronic
      increase in cellular superoxide has been implicated in the contributory
      mechanisms. Mitochondria are a major cellular site for superoxide generation at
      complexes I or III of the electron transport chain. Within the mitochondrial
      matrix, superoxide is converted to hydrogen peroxide though activity of Mn
      superoxide dismutase. A portion of the superoxide generated at complex III is
      also released into the mitochondrial intermembrane space, which contains a
      recently identified copper, zinc superoxide dismutase (Cu,ZnSOD). Deletion of
      Cu,ZnSOD has been shown to lead to a phenotype of accelerated age-related loss of
      skeletal muscle mass and function, although it is unclear whether loss of the
      enzyme in the intermembrane space or cytosol is important in this respect. It is
      hypothesized that the processes underlying loss of muscle mass and function in
      the Cu,ZnSOD knockout mice provide a model that can inform identification of the
      processes that occur during normal aging.

PMID- 20046123
TI  - Skeletal muscle response to inflammation--lessons for chronic obstructive
      pulmonary disease.
AB  - To describe how inflammation affects muscle adaptation and performance in people
      with chronic obstructive pulmonary disease. In chronic obstructive pulmonary
      disease, an increasingly sedentary lifestyle is a primary contributor to muscle
      dysfunction that results in a loss of mobility and independence and, ultimately,
      mortality. Given the systemic chronic inflammation and profound limb muscle
      atrophy in chronic obstructive pulmonary disease, it is tempting to speculate
      that the inflammatory process is deleterious to skeletal muscle. In healthy
      people, however, the inflammatory process initially is dominated by a destructive
      phase that is tightly regulated and modulates a reparative, regenerative phase.
      Although the inflammatory process and associated oxidative stress is more closely
      connected to muscle wasting in animal models of chronic obstructive pulmonary
      disease, the causative role of inflammation toward muscle atrophy and weakness in
      people with chronic obstructive pulmonary disease has not been definitively
      shown. Anti-inflammatory interventions aimed toward tempering muscle wasting and
      weakness in chronic obstructive pulmonary disease may not prove to be beneficial
      because of longer-term disruption of the regeneration of muscle tissue.
      Temporally and spatially targeted interventions aimed toward ameliorating
      oxidative stress, such as antioxidants, nutritional supplements, and chronic
      exercise training, may optimize outcomes toward maintaining muscle mass and
      performance.

PMID- 20046124
TI  - Muscle in defense.
AB  - The physical inactivity of the critically ill patient is an abnormal state that
      compromises muscle function to an extent that the immobile skeletal muscle may
      not simply be a bystander in the disease process.Skeletal muscle seems to
      maintain a system of defense against inflammation through heat shock proteins and
      the production of myokines. It contributes in a bidirectional role in systemic
      inflammatory signaling and the modulation of the inflammatory response. Skeletal
      muscle is a major contributor to whole-body glucose and protein metabolism,
      exemplified by its role in nutrient provision for the immune system and other
      rapidly dividing tissues through glutamine production.

PMID- 20046121
TI  - Sepsis-induced myopathy.
AB  - Sepsis is a major cause of morbidity and mortality in critically ill patients,
      and despite advances in management, mortality remains high. In survivors, sepsis
      increases the risk for the development of persistent acquired weakness syndromes
      affecting both the respiratory muscles and the limb muscles. This acquired
      weakness results in prolonged duration of mechanical ventilation, difficulty
      weaning, functional impairment, exercise limitation, and poor health-related
      quality of life. Abundant evidence indicates that sepsis induces a myopathy
      characterized by reductions in muscle force-generating capacity, atrophy (loss of
      muscle mass), and altered bioenergetics. Sepsis elicits derangements at multiple
      subcellular sites involved in excitation contraction coupling, such as decreasing
      membrane excitability, injuring sarcolemmal membranes, altering calcium
      homeostasis due to effects on the sarcoplasmic reticulum, and disrupting
      contractile protein interactions. Muscle wasting occurs later and results from
      increased proteolytic degradation as well as decreased protein synthesis. In
      addition, sepsis produces marked abnormalities in muscle mitochondrial functional
      capacity and when severe, these alterations correlate with increased death. The
      mechanisms leading to sepsis-induced changes in skeletal muscle are linked to
      excessive localized elaboration of proinflammatory cytokines, marked increases in
      free-radical generation, and activation of proteolytic pathways that are upstream
      of the proteasome including caspase and calpain. Emerging data suggest that
      targeted inhibition of these pathways may alter the evolution and progression of
      sepsis-induced myopathy and potentially reduce the occurrence of sepsis-mediated
      acquired weakness syndromes.

PMID- 20046125
TI  - Metabolic aspects of critical illness polyneuromyopathy.
AB  - Critically ill patients frequently develop muscle weakness due to critical
      illness-related acute neuropathy and/or myopathy. This is a frequent disorder,
      with important short-term consequences that include difficulties in weaning from
      mechanical ventilation, associated prolonged intensive care unit and hospital
      stay, and increased mortality rates. In addition, many patients continue to
      suffer from decreased exercise capacity and quality of life for months to years
      after the acute event. Many different mechanisms seem to be involved in the
      development of this process. In this review, we will focus on the metabolic
      aspects of critical illness-related acute neuropathy and/or myopathy and, more
      specifically, on our clinical experience with achieving strict glycemic control
      using insulin. Our group has performed two randomized controlled trials in
      surgical and medical critically ill patients and studied the occurrence of
      critical illness-related acute neuropathy and/or myopathy and delayed weaning,
      one of its most important complications. Potential underlying mechanisms derived
      from experimental studies and from the analysis of biopsy samples harvested from
      critically ill patients or patients suffering from other catabolic states are
      discussed.

PMID- 20046126
TI  - Anabolic resistance in critically ill patients.
AB  - Most patients who are critically ill lose muscle as a result of an inability to
      maintain rates of protein synthesis above those of protein breakdown. In addition
      to the effects of a procatabolic hormonal and cytokine milieu, which accelerate
      protein breakdown, age and immobility also influence the ability of muscle to
      maintain itself. Although the basal rates of protein turnover are not altered
      with aging, age is associated with a smaller ability to capture blood-borne amino
      acids as protein, the results of a decreased capacity for protein synthesis
      (total RNA/DNA) and decreased sensitivity and capacity of signaling proteins to
      indicate the availability of amino acids. Furthermore, muscle of older
      individuals is resistant to the effects of insulin in decreasing muscle
      proteolysis. Both of these effects are part of "anabolic resistance"-the
      inability of muscle to maintain its protein mass by appropriate stimulation of
      muscle protein turnover and inhibition of protein breakdown. Overlain on the
      effects of age are the effects of immobility, which has some of the
      characteristics of anabolic resistance. Immobility per se causes a decrease in
      muscle protein synthesis with no apparent stimulation of muscle protein
      breakdown; furthermore, muscle of immobilized legs is unable to stimulate muscle
      protein synthesis to the same extent as that of nonimmobilized legs when amino
      acids are infused, even at high rates.

PMID- 20046127
TI  - Performance-enhancing sports supplements: role in critical care.
AB  - Many performance-enhancing supplements and/or drugs are increasing in popularity
      among professional and amateur athletes alike. Although the uncontrolled use of
      these agents can pose health risks in the general population, their clearly
      demonstrated benefits could prove helpful to the critically ill population in
      whom preservation and restoration of lean body mass and neuromuscular function
      are crucial. Post-intensive care unit weakness not only impairs post-intensive
      care unit quality of life but also correlates with intensive care unit mortality.
      This review covers a number of the agents known to enhance athletic performance,
      and their possible role in preservation of muscle function and
      prevention/treatment of post-intensive care unit weakness in critically ill
      patients. These agents include testosterone analogues, growth hormone, branched
      chain amino acid, glutamine, arginine, creatine, and beta-hydryoxy-beta
      methylbutyrate. Three of the safest and most effective agents in enhancing
      athletic performance in this group are creatine, branched-chain amino acid, and
      beta-hydryoxy-beta-methylbutyrate. However, these agents have received very
      little study in the recovering critically ill patient suffering from post
      intensive care unit weakness. More placebo-controlled studies are needed in this
      area to determine efficacy and optimal dosing. It is very possible that, under
      the supervision of a physician, many of these agents may prove beneficial in the
      prevention and treatment of post-intensive care unit weakness.

PMID- 20046128
TI  - What is the proper approach to liberating the weak from mechanical ventilation?
AB  - The general issue of weaning can be viewed as composed of three different groups
      of patients. First, simple or easy weaning, represents 60% to 70% of patients
      whose first trial of spontaneous breathing is successful. The main objective of
      the weaning process is to detect weaning readiness as early as possible, which is
      best achieved using a systematic approach. The percentage of patients in this
      group in a given intensive care unit represents the pretest probability of
      weaning. A second group is made of patients who experience failure of the first
      spontaneous breathing trial and in whom up to 7 days from the first trial may be
      required to achieve weaning. This group represents 20% to 25% of patients who
      undergo weaning from mechanical ventilation. Muscle weakness contributes to the
      prolongation of weaning in many of these patients. The last group is made of
      patients who are characterized by a prolonged or very difficult weaning process
      (about 5% to 15% of patients undergoing weaning). Muscle weakness is likely to be
      a major contributing factor. Early use of spontaneous breathing, well-controlled
      use of sedation, and early mobilization may help in reducing muscle weakness and
      hasten the weaning process. The postextubation period may be particularly at risk
      in these patients. More research is needed to guide clinicians regarding the best
      ventilatory management.

PMID- 20046129
TI  - Role of analgesics, sedatives, neuromuscular blockers, and delirium.
AB  - A major focus on critical care medicine concerns the institution of life-support
      therapies, such as mechanical ventilation, during periods of organ failure to
      permit a window of opportunity to diagnose and treat underlying disorders so that
      patients may be returned to their prior functional status upon recovery. With the
      growing success of these intensive care unit-based therapies and longer-term
      follow-up of patients, severe weakness involving the peripheral nervous system
      and muscles has been identified in many recovering patients, often confounding
      the time course or magnitude of recovery. Mechanical ventilation is often
      accompanied by pharmacologic treatments including analgesics, sedatives, and
      neuromuscular blockers. These drugs and the encephalopathies accompanying some
      forms of critical illness result in a high prevalence of delirium in mechanically
      ventilated patients. These drug effects likely contribute to an impaired ability
      to assess the magnitude of intensive care unit-acquired weakness, to additional
      time spent immobilized and mechanically ventilated, and to additional weakness
      from the patient's relative immobility and bedridden state. This review surveys
      recent literature documenting these relationships and identifying approaches to
      minimize pharmacologic contributions to intensive care unit-acquired weakness.

PMID- 20046130
TI  - Consequences of bed rest.
AB  - Bed rest is frequently prescribed for critically ill patients because it is
      assumed to be beneficial for preventing complications, for conserving scarce
      metabolic resources, and for providing patient comfort. Furthermore, higher
      levels of physical activity in critically ill patients have been assumed to be
      impractical or not feasible. Bed rest has been prescribed in the past for several
      other clinical conditions including acute flares of rheumatoid arthritis,
      cavitary tuberculosis, acute myocardial infarction, and acute low back pain.
      However, randomized, controlled, clinical trials failed to demonstrate beneficial
      effects of bed rest in most of these conditions. Bed rest can cause several
      complications that may delay or prevent recovery from critical illnesses
      including disuse muscle atrophy, joint contractures, thromboembolic disease, and
      insulin resistance. Recent studies demonstrated the feasibility and safety of
      physical medicine programs in critically ill patients including those with acute
      respiratory failure requiring mechanical ventilation. Other physical medicine
      tools, such as neuromuscular electrical stimulation and passive stretching of
      muscles, may also reduce some complications of bed rest.

PMID- 20046131
TI  - Culture of early mobility in mechanically ventilated patients.
AB  - Physical deconditioning and prolonged motor weakness accompanying critical
      illness have profound and lasting consequences for both patients and their
      informal caregivers. The etiology is multifactorial and the effects may be
      mitigated by an early mobility process. Early mobility is facilitated by change
      in intensive care unit culture that requires clinicians to: 1) reorganize and
      manage current practices that have the potential to interfere with mobility; 2)
      create a strategy to improve the level of teamwork; and 3) link effective
      practice intervention and teamwork with short- and long-term patient-centered
      outcomes.

PMID- 20046132
TI  - Technology to enhance physical rehabilitation of critically ill patients.
AB  - BACKGROUND: Neuromuscular complications after critical illness are common and can
      be severe and persistent. To ameliorate complications, there is growing interest
      in starting physical medicine and rehabilitation therapy immediately after
      physiologic stabilization. The introduction of physical medicine and
      rehabilitation-related technology into the intensive care unit may help
      facilitate delivery of this therapy. DISCUSSION: Neuromuscular electrical
      stimulation therapy creates passive contraction of muscles through low-voltage
      electrical impulses delivered through skin electrodes placed over target muscles.
      Although neuromuscular electrical stimulation has not been studied in patients
      with acute critical illness, published guidelines based on available evidence
      suggest that neuromuscular electrical stimulation may be considered in intensive
      care unit patients who are at high risk of developing muscle weakness. Bedside
      cycle ergometry can provide range of motion and muscle strength training for
      intensive care unit patients who are either sedated or awake, and may help
      preserve muscle architecture and improve strength and function. Finally, custom
      designed technological aids to assist with ambulating mechanically ventilated
      patients may reduce the human resource requirements and improve the safety and
      effectiveness of early mobilization in the intensive care unit. CONCLUSION:
      Physical medicine and rehabilitation-related technologies may play an important
      role in preventing and treating intensive care unit-acquired neuromuscular
      complications. Future studies are needed to evaluate their efficacy in intensive
      care unit patients.

PMID- 20046133
TI  - Clinical trials of early mobilization of critically ill patients.
AB  - Intensive care unit-acquired weakness is a common complication of critical
      illness leading to severe functional impairment in many intensive care unit
      survivors. Critically ill patients who require mechanical ventilation are
      routinely immobilized for prolonged time periods. This immobilization is
      exacerbated by frequent administration of sedative agents. Recently, several
      investigators have described the feasibility and potential benefits of mobilizing
      mechanically ventilated intensive care unit patients. Such an intervention
      requires a multidisciplinary team approach to patient care, involving nursing,
      physical therapy, occupational therapy, and respiratory therapy practitioners.
      Recent studies of early mobilization of mechanically ventilated intensive care
      unit patients have noted this intervention to be safe and associated with
      improved functional outcomes in this extremely ill patient cohort. Such outcomes
      include high percentages of patients able to ambulate on intensive care unit and
      hospital discharge and shortened hospital length of stay. With preliminary
      studies demonstrating remarkable feasibility and successes, further prospective
      studies of early mobilization are needed to evaluate this intervention.

PMID- 20046134
TI  - Assessing burden in families of critical care patients.
AB  - OBJECTIVE: To provide critical care clinicians with information on validated
      instruments for assessing burden in families of critical care patients. DATA
      SOURCES: PubMed (1979-2009). STUDY SELECTION: We included all quantitative
      studies that used a validated instrument to evaluate the prevalence of, and risk
      factors for, burden on families. DATA EXTRACTION AND SYNTHESIS: We extracted the
      descriptions of the instruments used and the main results. Family burden after
      critical illness can be detected reliably and requires preventive strategies and
      specific treatments. Using simple face-to-face interviews, intensivists can learn
      to detect poor comprehension and its determinants. Instruments for detecting
      symptoms of anxiety, depression, or stress can be used reliably even by
      physicians with no psychiatric training. For some symptoms, the evaluation should
      take place at a distance from intensive care unit discharge or death. Experience
      with families of patients who died in the intensive care unit and data from the
      literature have prompted studies of bereaved family members and the development
      of interventions aimed at decreasing guilt and preventing complicated grief.
      CONCLUSIONS: We believe that burden on families should be assessed routinely. In
      clinical studies, using markers for burden measured by validated tools may
      provide further evidence that effective communication and efforts to detect and
      to prevent symptoms of stress, anxiety, or depression provide valuable benefits
      to families.

PMID- 20046135
TI  - Legacy of intensive care unit-acquired weakness.
AB  - Loss of muscle mass, nerve dysfunction, and resultant weakness and functional
      disability represent important and lasting morbidities of an episode of critical
      illness. As investigators increasingly incorporate long-term functional,
      neuropsychological, and quality-of-life outcomes into their studies, more data
      are accruing that support the existence of often devastating and irreversible
      sequelae of severe illness and treatment in an intensive care unit. This review
      highlights early quality-of-life literature that supports significant physical
      dysfunction after intensive care unit treatment and more recent longitudinal
      studies up to 5 yrs after intensive care unit discharge, which clearly implicate
      nerve and muscle dysfunction as contributors to this reported disability.
      Additional follow-up work is needed to understand the pathophysiology of this
      injury, the spectrum of physical disability, and its associated risk factors.
      These data are crucial to inform risk-stratification and future rehabilitation
      interventions, both during the intensive care unit admission and after hospital
      discharge as patients reintegrate within their community and workplace.

PMID- 20046137
TI  - Current world literature.

PMID- 20046141
TI  - Monitoring for treatment failure in patients on first-line antiretroviral
      treatment in resource-constrained settings.
AB  - PURPOSE OF REVIEW: The number of people living with HIV in low-income and middle
      income countries (LMICs), who will fail first-line treatment and benefit from
      regimen switching, will steadily increase in the coming years. The diagnosis of
      treatment failure in many settings is challenging because of limited access to
      plasma HIV RNA testing. This article summarizes recent studies in LMICs,
      investigating the diagnosis of treatment failure. RECENT FINDINGS: WHO
      recommended clinico-immunological criteria to identify first-line treatment
      failure, which have a low sensitivity and positive predictive value. The addition
      of adherence criteria or alternative clinical and laboratory markers improves
      performance, but overall the results are suboptimal. This situation leads to both
      delayed and inappropriately premature switching to more expensive second-line
      agents. The cost-effectiveness of alternative monitoring strategies is debated,
      but there is increasing interest in the use of viral load testing to confirm
      virological failure before switching to second-line therapy. However, access to
      viral load testing in LMICs remains limited and a simple point-of-care assay is
      not yet available. SUMMARY: Monitoring the efficacy of antiretroviral therapy in
      LMICs remains a critical challenge. Current research priorities include the
      development of simpler, cheaper assays and optimizing monitoring strategies based
      on currently available technologies.

PMID- 20046142
TI  - When to start antiretroviral therapy in adults in low- and middle-income
      countries: science and practice.
AB  - PURPOSE OF REVIEW: To review data related to the outcomes of antiretroviral
      therapy (ART) and the current operational experiences of ART programmes in low
      income and middle-income countries (LMICs), concentrating on the implications and
      feasibility of changing ART initiation practice. RECENT FINDINGS: ART initiation
      practice inhigh-income country settings has been modified in favour of starting
      ART earlier, basing on early evidence that HIV-associated morbidity and mortality
      are significantly reduced, and because there are increasingly more potent less
      toxic antiretroviral drug options available.In LMICs, ART initiation continues to
      follow conservative practice. At the same time, reports from ART programmes in
      low-income settings continue to demonstrate great benefits in terms of survival
      for people with HIV. However, compared with high-income country settings, the
      clinical outcomes of ART in LMICs are less favourable. The enormous HIV disease
      burden coupled with weaker health service capability is a key challenge to
      expanding ART effectively, although, as ART programmes mature, there are early
      indications that patient outcomes may be improving. SUMMARY: In the immediate
      term, whether it is feasible to move to wide-scale earlier initiation of ART in
      LMICs remains in question; the priority for many countries is still equity and
      meeting the unmet needs for treatment. However, the possibility that early ART
      could reduce the risk of HIV transmission presents a particularly compelling
      incentive for earlier treatment in the high-burden settings of LMICs and further
      evidence on this rationale is anticipated from ongoing and planned studies.

PMID- 20046143
TI  - Early versus deferred antiretroviral therapy in children in low-income and middle
      income countries.
AB  - PURPOSE OF REVIEW: We reviewed current literatures on early and deferred
      initiation of antiretroviral therapy in HIV-infected infants and children in low
      income and middle-income countries. RECENT FINDINGS: Data from children with HIV
      antiretroviral (Children with HIV Early Antiretroviral Therapy) study showed a
      significant reduction of 76% in mortality among infants who received
      antiretroviral therapy within 3 months of their life as opposed to those on
      deferred therapy. These data led World Health Organization to promptly revise the
      guideline to recommend initiation of antiretroviral therapy in all HIV-infected
      infants regardless of clinical or immunological status. The recommendation for
      older children is differed between guidelines of developed and developing
      countries. In general, higher CD4 cell count threshold is used for younger
      children and similar criteria to those used for adults are used once children are
      above 5 years of age. The randomized study of when to start antiretroviral
      therapy in children older than 1 year is ongoing. SUMMARY: The current trend is
      to move toward early treatment to reduce morbidity and mortality, achieve immune
      recovery, normal growth, and development. Even though the antiretroviral rollout
      program has been successful in Asia and Africa, the challenges lie in diagnosing
      infants in a timely manner and maintaining infrastructure and resources to
      support life-long treatment.

PMID- 20046145
TI  - Resistance considerations in sequencing of antiretroviral therapy in low-middle
      income countries with currently available options.
AB  - PURPOSE OF REVIEW: Access to antiretroviral therapy (ART) has been scaled-up in
      low-middle income countries (LMICs), where the majority of the world's HIV-1
      infected population is living. Concerns towards the emergence and spread of HIV-1
      drug resistance exist, given the lack of virological monitoring which may give
      rise to accumulation of resistance as well as the use of suboptimal ART in
      pregnant women with the aim to reduce perinatal transmission. Knowledge of the
      prevalence of transmitted and emerging drug resistance as well as its specific
      patterns is of help in guiding the selection of appropriate ART types and
      sequencing strategies. RECENT FINDINGS: Whereas transmitted drug resistance in
      LMIC is still limited, resistance in pregnant women as a consequence of
      suboptimal ART for the prevention of vertical transmission is frequent and
      dependent on viral subtype and load. Accumulation of drug resistance during first
      line ART depends on the frequency of monitoring, whereas mutational patterns are
      influenced by type of ART and, partly, viral subtype. SUMMARY: Optimized ART for
      prevention of mother-to-child transmission and closer monitoring of ART programs
      with the inclusion of viral load may help reducing unnecessary development of HIV
      drug resistance in LMIC and preserve the limited available treatment options.

PMID- 20046144
TI  - Strategies to reduce early morbidity and mortality in adults receiving
      antiretroviral therapy in resource-limited settings.
AB  - PURPOSE OF REVIEW: We review recently published literature concerning early
      morbidity and mortality during antiretroviral therapy (ART) among patients in
      resource-limited settings. We focus on articles providing insights into this
      burden of disease and strategies to address it. RECENT FINDINGS: In sub-Saharan
      Africa, mortality rates during the first year of ART are very high (8-26%), with
      most deaths occurring in the first few months. This figure compares with 3-13% in
      programmes in Latin America and the Caribbean and 11-13% in south-east Asia. Risk
      factors generally reflect late presentation with advanced symptomatic disease.
      Key causes of morbidity and mortality include tuberculosis (TB), acute sepsis,
      cryptococcal meningitis, malignancy and wasting syndrome/chronic diarrhoea.
      Current literature shows that the fundamental need is for much earlier HIV
      diagnosis and initiation of ART. In addition, further studies provide data on the
      role of screening and prophylaxis against opportunistic diseases (particularly
      TB, bacterial sepsis and cryptococcal disease) and the management of specific
      opportunistic diseases and complications of ART. Effective and sustainable
      delivery of these interventions requires strengthening of programmes. SUMMARY:
      Strategies to address this disease burden should include earlier HIV diagnosis
      and ART initiation, screening and prophylaxis for opportunistic infections,
      optimized management of specific diseases and treatment complications, and
      programme strengthening.

PMID- 20046146
TI  - Improving first-line antiretroviral therapy in resource-limited settings.
AB  - PURPOSE OF REVIEW: Access to first-line antiretroviral therapy in resource
      limited settings has increased rapidly in the last 5 years. Newer medicines with
      greater potency and better safety profiles open the possibility for improving
      first-line antiretroviral therapy for developing countries. RECENT FINDINGS:
      Several medicines offer the potential to improve the simplicity, safety and
      efficacy of first-line antiretroviral therapy in resource-limited settings. These
      include tenofovir, raltegravir, elvitegravir, rilpivirine and protease
      inhibitors. A number of clinical questions are outstanding, particularly
      regarding safety in pregnancy and compatibility with drugs to treat common
      coinfections including tuberculosis. SUMMARY: Simple, affordable regimens were
      key to the initial emergency response, but the long-term response to HIV calls
      for a reconsideration of current treatment options. Preconditions for widespread
      use in developing countries include affordability, simplicity and answers to
      relevant research questions. In the absence of strong pharmacovigilance systems,
      cohort monitoring will be critical to assessing the safety profile of new drugs
      in such settings.

PMID- 20046147
TI  - Use of antiretrovirals during pregnancy and breastfeeding in low-income and
      middle-income countries.
AB  - PURPOSE OF REVIEW: The purpose of the study was to review recent evidence on the
      use of antiretrovirals during pregnancy and breastfeeding in low-income and
      middle-income settings. RECENT FINDINGS: Access to antiretroviral prophylaxis
      strategies for HIV-infected pregnant women has increased globally, but two-thirds
      of women in need still do not receive even the simplest regimen for the
      prevention of mother-to-child transmission of HIV, and most pregnant women in
      need of antiretroviral treatment do not receive it. The use of combination
      antiretroviral treatment in pregnancy in low-resource settings is safe and
      effective, and increasing evidence supports starting ongoing antiretroviral
      treatment at a CD4 cell count below 350/microl in pregnant women. The use of
      appropriate short-course antiretroviral prophylactic regimens is effective for
      prevention of mother-to-child transmission of HIV in women with higher CD4 cell
      counts. New data on the use of antiretroviral prophylaxis to prevent transmission
      through breastfeeding demonstrate that both maternal antiretroviral treatment and
      extended infant prophylaxis are effective. SUMMARY: Antiretroviral use in
      pregnancy can benefit mothers in need of treatment and reduce the risk of mother
      to-child transmission. Emerging evidence of the effectiveness of antiretroviral
      prophylaxis in preventing transmission through breastfeeding is encouraging and
      likely to influence practice in the future.

PMID- 20046148
TI  - Sequencing of antiretroviral therapy in children in low- and middle-income
      countries.
AB  - PURPOSE OF REVIEW: With recent changes in global pediatric HIV policy to initiate
      treatment immediately after early infant diagnosis, there will be greater demand
      for feasible antiretroviral sequencing strategies that will support children
      through adulthood. This review will discuss HIV treatment (antiretroviral
      therapy) failure, regimen switching, and sequencing approaches in children.
      RECENT FINDINGS: Although children appear to acquire resistance mutations in a
      similar pattern to adults, they may develop virologic failure more rapidly;
      reports from Africa and Asia have already documented rates as high as 26% at 12
      months of antiretroviral therapy. Ritonavir-boosted lopinavir is recommended
      after failure to nonnucleoside reverse transcriptase inhibitors; efavirenz is the
      preferred nonnucleoside reverse transcriptase inhibitor after protease inhibitor
      failure. Approaches to sequencing nucleoside reverse transcriptase inhibitors are
      more complicated, as accumulated resistance mutations may render currently
      recommended combinations less potent. Salvage regimens are preferably selected
      after genotyping, and may require the use of expensive, novel boosted protease
      inhibitors and new drug classes (e.g., integrase inhibitors). SUMMARY: Data on
      drug resistance in children in low- and middle-income countries are emerging and
      will guide future sequencing strategies. Lack of access to treatment monitoring
      and second-line and salvage drugs are key limiting factors that need to be
      addressed in order to ensure ongoing treatment success.

PMID- 20046150
TI  - Antiretroviral therapy adherence and retention in care in middle-income and low
      income countries: current status of knowledge and research priorities.
AB  - PURPOSE OF REVIEW: Adherence to combination antiretroviral therapy (cART) is one
      of the most important contributing factors to positive clinical outcomes in
      patients with HIV, and long-term retention of patients in low-income and middle
      income countries is emerging as an important issue in rapidly expanding cART
      programs. This review presents recent developments in both treatment adherence
      and retention of patients in low-income and middle-income countries. RECENT
      FINDINGS: Adherence is among the most modifiable variables in treatment, but
      there still is no 'gold standard' measurement. Best estimates demonstrate that
      adherence in resource-limited settings is equal or superior to that in resource
      rich settings, possibly due to focused efforts on support groups and community
      acceptance of adherence behaviors. However, long-term data show that sustained
      efforts to ensure high cART adherence and evidence of intervention effects are
      critical, but that resource-intensive interventions are not warranted in settings
      where cART adherence is high. Furthermore, well conducted evaluation of
      culturally sensitive interventions to maximize pre-cART and post-cART initiation
      retention is badly needed in low-income and middle-income settings. SUMMARY:
      Further research is needed to identify risk factors and to improve adherence and
      retention among children, adolescents, and adults through use of social networks
      or emerging technologies for patients at risk for poor adherence.

PMID- 20046149
TI  - Management of individuals requiring antiretroviral therapy and TB treatment.
AB  - PURPOSE OF REVIEW: Globally, tuberculosis (TB) is the commonest opportunistic
      infection in people living with HIV. Many co-infected patients first present with
      advanced immunosuppression and require antiretroviral therapy (ART) initiation
      during TB treatment. The incidence of TB in patients established on ART remains
      high. Co-treatment presents several management challenges. Recent data on these
      management issues are reviewed. RECENT FINDINGS: Efavirenz concentrations at
      standard doses are similar with and without concomitant rifampicin-based TB
      treatment. Nevirapine concentrations are frequently subtherapeutic during lead-in
      dosing at 200 mg daily in patients on rifampicin-based TB treatment, which may
      result in inferior virological outcomes. Hepatotoxicity occurred in three
      pharmacokinetic studies (conducted in healthy volunteers) of boosted protease
      inhibitors initiated in participants on rifampicin. Results of a clinical trial
      comparing efavirenz-based and nevirapine-based ART in patients on TB treatment,
      with no lead-in dosing of nevirapine, are awaited. Concurrent TB treatment
      increases the need for stavudine substitutions, mainly related to neuropathy.
      Consensus case definitions for TB immune reconstitution inflammatory syndrome (TB
      IRIS) have been published. It is important to exclude TB drug resistance in
      patients with suspected TB-IRIS. A clinical trial demonstrated benefit of
      prednisone for treating TB-IRIS, reducing a combined endpoint of days of
      hospitalization and outpatient therapeutic procedures. Starting ART during TB
      treatment improved survival in patients with CD4 cell count less than 500
      cells/mul, but the optimal interval between starting TB treatment and starting
      ART remains to be determined in several ongoing trials. SUMMARY: ART improves
      survival in co-infected TB patients, but is complicated by several management
      challenges that compromise programmatic implementation in resource-limited
      settings. Recent findings and the findings of ongoing studies will assist
      clinicians in dealing with these challenges.

PMID- 20046151
TI  - Human resource aspects of antiretroviral treatment delivery models: current
      practices and recommendations.
AB  - PURPOSE OF VIEW: To illustrate and critically assess what is currently being
      published on the human resources for health dimension of antiretroviral therapy
      (ART) delivery models. RECENT FINDINGS: The use of human resources for health can
      have an effect on two crucial aspects of successful ART programmes, namely the
      scale-up capacity and the long-term retention in care. Task shifting as the
      delegation of tasks from higher qualified to lower qualified cadres has become a
      widespread practice in ART delivery models in low-income countries in recent
      years. It is increasingly shown to effectively reduce the workload for scarce
      medical doctors without compromising the quality of care. At the same time, it
      becomes clear that task shifting can only be successful when accompanied by
      intensive training, supervision and support from existing health system
      structures. SUMMARY: Although a number of recent publications have focussed on
      task shifting in ART delivery models, there is a lack of accessible information
      on the link between task shifting and patient outcomes. Current ART delivery
      models do not focus sufficiently on retention in care as arguably one of the most
      important issues for the long-term success of ART programmes. There is a need for
      context-specific re-designing of current ART delivery models in order to increase
      access to ART and improve long-term retention.

PMID- 20046152
TI  - Current and future management of treatment failure in low- and middle-income
      countries.
AB  - PURPOSE OF REVIEW: Access to second-line therapy in low- and middle-income
      countries has been limited to date. The WHO predicts that between 500 000 and 800
      000 HIV-infected people on first-line combination antiretroviral therapy will
      require switch to second-line therapy by 2010. This paper aims to describe and
      review access to second-line therapy in low- and middle-income countries at
      present and examine future possibilities. RECENT FINDINGS: The majority of HIV
      infected patients failing first-line combination antiretroviral therapy is
      identified by way of routine monitoring of clinical and immunological status as a
      surrogate for virological monitoring. Evidence suggests that immunological and
      clinical monitoring lack both sensitivity and specificity for virological
      failure. Consequently, at treatment failure, patients have often selected a
      degree of resistance within the nucleoside/nucleotide reverse transcriptase
      inhibitor class that questions the efficacy of using nucleoside/nucleotide
      reverse transcriptase inhibitors in a second-line regimen. There is a paucity of
      good-quality evidence on which to base guidelines and policy. Optimally, a second
      line regimen would be simple, potent, tolerable and lend itself to provision
      according to the successful 'public health' approach. SUMMARY: Provision of
      second-line therapy to HIV-infected individuals failing first-line therapy is a
      major challenge to the ongoing success of access to HIV care programmes in low-
      and middle-income countries. The optimal second-line combination antiretroviral
      therapies are unknown. Research trials to help define best practice are in
      advanced stages of development and implementation.

PMID- 20046153
TI  - Pharmacokinetics of low-dose protease inhibitors and efavirenz in low- and middle
      income countries.
AB  - PURPOSE OF REVIEW: The costs associated with antiretroviral therapy are becoming
      a major concern for the treatment of HIV-infected patients in resource-limited
      countries. Potential risk for the increase in toxicity due to higher drug
      exposure among Asians is also a concern. In this article, we discuss the studies
      performed using low-dose antiretroviral therapy as an effective and well
      tolerated strategy. RECENT FINDINGS: The studies reviewed demonstrate that dose
      reduction of antiretroviral therapy provides adequate plasma concentrations and
      effective immunological and virological responses in, mainly, a Thai population
      compared with whites. The differences in these pharmacokinetic parameters could
      possibly be due to differences in body weight and composition, drug-food
      interactions, metabolism, environmental factors and genetic background. Moreover,
      dose reduction can possibly decrease toxicity and save costs for patients in low-
      and middle-income countries. SUMMARY: Although the use of low-dose antiretroviral
      drugs showed adequate plasma levels in an Asian population, in particular,
      careful attention has to be given to pharmacokinetic, safety and efficacy data to
      avoid problems of subtherapeutic levels and drug resistance. Large, phase III
      studies are warranted.

PMID- 20046154
TI  - Estimation of antiretroviral therapy coverage: methodology and trends.
AB  - PURPOSE OF REVIEW: To present the methodology used to calculate coverage of
      antiretroviral therapy (ART) and review global and regional trends in ART
      coverage. RECENT FINDINGS: There has been a steady increase in ART coverage over
      the last decade with a more rapid increase in recent years. Current estimates of
      ART coverage are 43% for adults and 38% for children (ages 0-14 years). Methods
      for calculating coverage rely on good-quality patient monitoring systems in
      countries, and well informed models are needed to estimate the number of people
      in need of treatment. SUMMARY: The estimated coverage rates show that ART
      programs have improved over the past 8 years; however, approximately 58% (53-60%)
      of those people in need of ART are still not on treatment. High quality data are
      needed to accurately measure changes in ART coverage.

PMID- 20046155
TI  - Current world literature.

PMID- 20046156
TI  - Visfatin genotype may modify the insulin resistance and lipid profile in type 2
      diabetes patients.
AB  - AIM: We investigated the role of the -4689G/T promoter variant of the visfatin
      gene on serum visfatin concentration and biochemical markers in T2DM patient.
      METHODS: In a cross-sectional study we recruited 93 patients with type 2
      diabetes. Laboratory and anthropometric measurements were included FBG, OGTT,
      HbA1C, lipid Profile, fasting serum visfatin, fasting serum insulin, weight,
      height, Body Mass Index (BMI) and waist hip ratio (WHR). Genotyping for visfatin
      gene was performed by using the PCR-RFLP method. RESULTS: Our findings showed
      significant differences in levels of low density lipoprotein (LDL) cholesterol,
      total cholesterol, high density lipoprotein (HDL) cholesterol and fasting serum
      insulin among various types of visfatin genotype (TT, GG, and GT). This study
      showed a significant correlation between circulating levels of visfatin and
      weight, BMI, hs-CRP and fasting insulin in TT genotype. But regarding GG genotype
      only fasting insulin had a significant correlation with circulating visfatin.
      CONCLUSIONS: Visfatin genotypes may account for insulin resistance and levels of
      lipid profile that may cause by different visfatin expression between genotypes.

PMID- 20046157
TI  - Thyroid carcinoma risk in patients with hyperthyroidism and role of preoperative
      cytology in diagnosis.
AB  - AIM: The aim of this study was to determine the frequency of thyroid carcinoma in
      patients with hyperthyroidism and evaluate the role of preoperative
      ultrasonography (US) guided thyroid fine needle aspiration biopsy (FNAB) in
      diagnosis of thyroid carcinoma in these patients. METHODS: Three hundred twenty
      five hyperthyroid patients--119 with toxic multinodular goiter (TMNG), 47 with
      autonomous functioning toxic nodule (AFTN) and 159 with Graves Disease (GD)--were
      included in this study. All patients were evaluated with US and in all patients
      with nodules, US guided FNAB was carried out. RESULTS: Among 159 patients with
      GD, 62 were without nodules. Totally, 583 nodules in 263 patients were sampled by
      FNAB. Cytologic results of nodules were as follows: 87.7% benign, 6.2%
      inadequate, 4.3% suspicious and 1.9% malignant. Postoperatively, 42 (12.9%)
      patients were diagnosed as thyroid carcinoma histopathologically. Thyroid
      carcinoma was detected postoperatively in all patients with malignant cytology,
      in 47.8% of patients with suspicious cytology and in 44.4% of patients with
      inadequate cytology. Moreover, in 13 patients with benign cytology and in 3
      Graves patients without any nodule ultrasonographically, incidental thyroid
      carcinoma was found (5.7%). Consequently, thyroid malignancy rates were 16% in
      TMNG, 6.4% in AFTN and 12.6% in GD. CONCLUSION: Thyroid carcinoma is common in
      hyperthyroidism and FNAB is a reliable method in diagnosis of thyroid malignancy
      in these patients. Additionally, incidental thyroid carcinoma prevalence is also
      high in patients with hyperthyroidism. We suggest that it is reasonable to
      evaluate nodules with FNAB in hyperthyroid patients prior to radioactive iodine
      treatment or surgical intervention.

PMID- 20046158
TI  - Can we use ionized calcium in the evaluation of post-thyroidectomy hypocalcemia?
AB  - AIM: The postoperative hypocalcaemia has the higher incidence as complications
      related to thyroidectomy. METHODS: From 1 June 2006 to 30 June 2008, we examined
      492 patients operated on consecutively in our unit with a total thyroidectomy for
      thyroid disease. We evaluated the values of ionized calcium in all the cases,
      matching these with the preoperative and postoperative values of serum calcium.
      The pre- and postoperative (24 hours after treatment) data for ionized calcium
      and serum calcium were examined statistically with the Student's t-test; results
      with a P-value <0.05 were considered to be statistically significant. RESULTS:
      Two-hundred-and-twenty-three of the 492 patients (45.2%) treated with total
      thyroidectomy had preoperative values of ionized calcium lower than 1.13 mmol/L
      (normal values 1.13-1.32 mmol/L), while the ionized calcium values were lower
      than 1.10 mmol/L in 154 of the 223 patients. The mean value of ionized calcium in
      all 223 cases was 1.04+/-0.07 mmol/L. The mean serum calcium value in these
      patients was 9.13+/-0.291 mg/dL (normal values 8.3-10.5 mg/dL). In the other 259
      cases, the values of ionized calcium and serum calcium were 1.21+/-0.03 mmol/L
      and 9.1+/-0.29 mg/dL, respectively. In 75 cases on 223 with symptomatic
      hypocalcemia, the mean value of ionized calcium was 0.88+/-0.05 mmol/L, while, in
      the remaining 148 cases, the mean value was equal to 0.97+/-0.08 mmol/L
      (P<0.001). We compared this, in both groups, with the values of postoperative
      serum calcium; in the 75 cases with clinical hypocalcemia, the value of serum
      calcium was 7.32+/-0.35 mg/dL, while the value was equal to 8.4+/-0.34 mg/dL in
      the other cases (P<0.001). CONCLUSIONS: The values of ionized calcium must not be
      used as marker of hypocalcemia but must be seen as a diagnostic aid linked to
      others laboratory values, such as serum calcium.

PMID- 20046159
TI  - Genetic risk of breast cancer.
AB  - Several cutting-edge strategies are being used to evaluate candidate genetic risk
      factors for breast cancer. These include linkage analysis for mapping out BRCA1
      and BRCA2, mutational screening of candidate risk genes like CHEK2, ATM, BRIP1
      and PALB2, which are associated with an intermediate level of breast cancer risk.
      Genome-wide association studies have revealed several low-penetrance breast
      cancer risk alleles. The predisposition factors are associated with different
      levels of breast cancer risk. Relative to control population, the risk in
      patients harboring high-risk BRCA1 and 2 mutations is over 10-fold, with
      intermediate penetrance genes 2 to 4-fold and with low penetrance alleles less
      than 1.5-fold. Overall, these factors account for about 25% of the genetic risk
      for breast cancer. In the remainder, genetic factors to contribute to the risk of
      breast cancer remain unknown and are a subject of current investigation. With
      discovery and validation of newer and clinically relevant predisposition factors,
      additional breast cancer risk categories may be recognized. BRCA1 and BRCA2
      mutation testing allows identification of individuals at increased risk of breast
      cancer who are offered risk-reducing interventions. Targeted therapies are being
      developed that may refine management of patients with BRCA1 and BRCA2 mutations.
      Further genome-wide studies are required to identify clinically relevant
      molecular factors that will allow more accurate and widely applicable genetic
      risk stratification. Current efforts in discovery, validation and qualification
      of molecular markers of breast cancer risk offer considerable promise in the
      future to develop more accurate breast cancer risk assessment along with
      development of more effective chemopreventive and therapeutic strategies.

PMID- 20046160
TI  - Treatment of early breast cancer.
AB  - Surgical intervention for breast cancer has continually evolved. The current
      review reports on updates from the pivotal trials, examines areas of controversy,
      and explores possible future directions.

PMID- 20046161
TI  - Male osteoporosis.
AB  - Osteoporosis is a worldwide major public health problem, defined as "a systemic
      skeletal disease characterized by low bone mass and microarchitectural
      deterioration of bone tissue with a consequent increase in bone fragility and
      susceptibility to fractures". Osteoporosis is diagnosed by bone mineral density
      measurement (T-score of -2.5 or below) also in men. However, most of the studies
      carried out in the last decade focused on pathogenesis, diagnosis and treatment
      of osteoporosis in women. In spite of this, recent epidemiological and
      observational studies have shown that osteoporosis in men is an increasingly
      important clinical issue. In part because the world population is aging, it is
      likely that the total number of hip fractures in men in 2025 will be similar to
      current estimates in women. Furthermore 25-33% of men in some populations will
      sustain osteoporotic fractures in their lifetime. Nevertheless, male osteoporosis
      is still underdiagnosed and further studies are required to clarify the
      pathogenesis and find out the right therapy. Prevention and early diagnosis are,
      nowadays, the best ways of treatment.

PMID- 20046162
TI  - Aliskiren: a new inhibitor of renin-angiotensin aldosterone system activity.
AB  - The importance of renin-angiotensin aldosterone system (RAAS) in cardiovascular
      and renal diseases has long ago been recognized. However despite the availability
      of many effective drugs, such as angiotensin-converting enzyme (ACE) inhibitors
      and angiotensin receptor blockers, RAAS blockade is incomplete in several
      patients with consequent uncontrolled high blood pressure and not efficacy
      cardiovascular and renal protection. Aliskiren is a new renin inhibitor that
      block the RAAS at its origin. Recent studies suggest that Aliskiren reduces blood
      pressure, inhibits plasma renin activity and attenuates renal damage in diabetic
      patients with nephropathy. This review summarized the results of the more
      important studies performed in hypertensive and diabetic patients in which
      Aliskiren showed to be a safe and effective antihypertensive agent that can be
      used in monotherapy or in combination with other drugs to provide additional
      options to improve blood pressure control.

PMID- 20046163
TI  - Seroprevalence of human brucellosis among the population at risk in rural area.
AB  - This study was performed to evaluate the seroprevalence of brucellosis among the
      risk group of population. A cross sectional study was carried out in the
      Department of Microbiology, Mymensingh Medical College in collaboration with the
      Department of Medicine under the Faculty of Veterinary Science, Bangladesh
      Agricultural University, Mymensingh, between the period from July 2007 to June
      2008. A total of 210 samples were included in this study from risk group of
      population. A variety of serological tests have been applied for detection of
      antibodies against Brucella spp. Among the 210 subjects from risk group of
      population, 9(4.28%), 7(3.33%) and 7(3.33%) were positive for brucellosis by
      slide agglutination test, rose bengal plate agglutination test (RBPA) and
      standard tube agglutination test (STAT) respectively. Out of total specimen 10
      positive and 29 negative serum as detected by slide agglutination, rose bengal
      plate agglutination test (RBPT) and STAT were also examined by Enzyme linked
      immunosorbent assay (ELISA) for detection of IgG. Among them, 10 were positive by
      ELISA IgG. Seroprevalence among occupational groups were 11.11% in veterinary
      personnel, 6.45% in dairy workers and 4.67% in animal farmers. This study
      indicated that brucellosis is not uncommon at rural area of Mymensingh region in
      Bangladesh. It was suggested to conduct community survey and to plan properly the
      measures of control and prevention.

PMID- 20046164
TI  - Platelet count in 100 cases of pregnancy induced hypertension.
AB  - Hypertensive disorders are most common medical complication of pregnancy and the
      major causes of maternal & perinatal disease and death worldwide. The aim of the
      study was to see the platelet count in pregnancy induced hypertension (PIH). It
      was a prospective study. The study was done on 100 cases of PIH patients in Gynae
      & Obstetrics department of Mymensingh Medical College Hospital (MMCH) during the
      period of January to July 2006. Among the 100 cases 60 were eclamptic, 34 were
      pre eclamptic (PE) and 06 were gestational hypertensive (GH) patients. All the
      necessary informations and data were collected by interviewing the patients or
      their attendants on a pre-designed data collection sheet. Blood sample were
      collected from the patients and required investigations were done. Most of the
      eclampsia cases were from below average socioeconomic status of family, and other
      two groups were from average socioeconomic status of family. Among eclamptic
      patients 76.60% were primigravida. In eclamptic group 93.33% did not get any
      antenatal care but 83.33% GH cases had regular antenatal care. Among the
      eclamptic group mean maternal age was 23.12 years. In our study 47.00% had low
      platelet count (<1,50,000/cmm). Among eclampsia group 60.00% had low platelet
      count (<1,50,000/cmm). In our study 12% cases developed postpartum haemorrhage
      (PPH) and among them 66.67% had low platelet count (<1,50,000/cmm). Although
      there is chance of development of disseminated intravascular coagulation (DIC)
      and Liver Failure in patients with low platelet count, but in our study there is
      no such incidence. In our study mortality was 3% and all were in eclamptic group.
      Those patients had low platelet count 74.28% had low birth weight (LBW) babies.
      Platelet count is a very important investigation for antenatal mother having PIH,
      as it is directly related to maternal and perinatal outcome.

PMID- 20046165
TI  - Preliminary report on anaerobic culture at Mymensingh Medical College Hospital in
      Bangladesh.
AB  - Puerperal sepsis is an important cause of maternal morbidity and mortality in
      developing countries. This study was undertaken to isolate and identify the
      anaerobic bacterial agents of puerperal sepsis among the patients admitted in
      Mymensingh Medical College Hospital (MMCH) during the period from July 2006 to
      June 2007. Endocervical swabs/secretions were collected from 50 cases of
      puerperal sepsis and were cultured anaerobically. Anaerobiasis was done by using
      gas pack (BD GAS PAK TM EZ) in anaerobic jar. Out of 50 samples, 42(84%) yielded
      growth in cultures. Among 42 culture positive cases, 20(40%) were Aerobic
      organisms and 22(44%) were mixed, i.e., Aerobic and Anaerobic bacteria. The
      isolated Anaerobic organisms were Peptostreptococcus 14(63.63%), Bacteroides
      fragilis 3(13.64%), Prevotella melaninogenica 3(13.64%) and Clostridium
      perfringens 2(9.09%). As a preliminary study, it was observed that anaerobic
      culture could be carried out with available logistic arrangement. So, it was
      recommended to design further study on anaerobic bacterial isolation with
      particular emphasis on their antimicrobial susceptibility.

PMID- 20046166
TI  - Molecular characterization of group A human rotavirus among hospitalized children
      and adults in Bangladesh: finding of emerging G12 strain.
AB  - Between July 2004 and June 2006, a total of 1438 fecal samples were collected
      from Hospitalized children and adults with diarrhea at an Infectious Disease
      Hospital (SK Hospital) in Mymensingh, Bangladesh. The diversity of rotavirus
      strains were investigated using electropherotyping and reverse transcription-PCR
      amplification of the VP7 and VP4 genes. Group A rotavirus was detected in 171 of
      1438(11.9%) specimens: 13.3%(72/543) from children 6 months to </=15 years of age
      and 11.0%(99/895) from individuals aged >15-76 years. The electrophoretic
      patterns of dsRNA of rotavirus showed 11 different migrations (7 long and 4
      short) by polyacrylamide gel electrophoresis (PAGE). Representative 60 positive
      samples were selected for PCR genotyping. For the entire period, the common
      rotavirus G types G1 (27%), G2 (45%), and G9 (7%), comprised 79% of the strains,
      and common P types, P[4] (43%), P[6] (12%), and P [8] (20%), comprised 75% of the
      total P types. Of note, we detected a high percentage of unusual G-type P-type
      combination (11%) strains and specimens with mixed (10% G and 23% P) rotavirus
      infection with a variety of genomic constellation. Overall, the most frequent
      rotavirus strains were G2P[4] (36.7%) both in children and adults which were
      mostly associated with VP6 genotype I (subgroup I), and NSP4 genotype A or B,
      followed by G1P[8] (10.0%), G9P[8] (6.7%). G12 was detected for the first time in
      the study area and the detection rate was G12P[6] (3.4%), and G12P[4] (1.7%). The
      nucleotide sequence of VP7 gene was highly homologous among G12 strains isolated
      in Mymensingh suggesting recent emergence from a common ancestor. The study
      highlighted the diversity of rotaviruses isolated from children and adults. Due
      to the effect of antigenic diversity on rotavirus vaccines, it is important to
      continue careful monitoring of these strains as rotavirus vaccine programs are
      being implemented in Bangladesh.

PMID- 20046167
TI  - Comparison between the effects of alcohol and hexane extract of spirulina in
      arsenic removal from isolated tissues.
AB  - Chronic arsenic poisoning (arsenicosis) is a major public health problem in
      Bangladesh. People are consuming high concentration of arsenic (>10 ppb) through
      their drinking water. But still now, there is no specific treatment of it.
      Spirulina, natural bluish-green microalgae, is found to be effective in the
      treatment of arsenicosis recently. Keeping this fact in mind the present study
      was conducted in the Department of Pharmacology, BSMMU to compare the
      effectiveness of alcohol & Hexane extract of Spirulina in arsenic removal from
      isolated tissues (rat liver). The experiment was performed in two phases-in phase
      I, liver tissues incubated with arsenic at 37 degree centigrade at different
      incubation period & accumulation of arsenic was measured. In phase II, arsenic
      loaded liver tissues were incubated at 37 degree centigrade in presence and
      absence of alcohol extract & hexane extract of spirulina. Arsenic removal (%)
      from liver tissues by alcohol extract and hexane extract of spirulina was
      estimated by Atomic Absorption Spectrophotometer. This study showed that there is
      time dependent accumulation of arsenic in isolated liver tissue and highest
      accumulation found was 0.69 microg/g tissues after 45 minutes incubation, which
      was highly significant. Removal of arsenic (%) from arsenic loaded liver tissues
      by alcohol extract & hexane extracts were 33.8% & 83.0% respectively. Between the
      two extracts of spirulina the hexane extract causes more percentage removal of
      arsenic which is highly significant (p<0.001). So, the present study suggests
      hexane extract of spirulina is more effective in removal of arsenic from rat
      liver tissues than alcohol extract.

PMID- 20046168
TI  - Demography and findings of reported rape cases.
AB  - Six hundred and ninety nine cases of alleged rape were studied by the authors
      during the period from 2007-2008 at the Mymensingh Medical College, Mymensingh.
      Of these cases, 122 had positive findings of recent sexual intercourse; 250 cases
      had the positive findings of habituated sexual intercourse, and 327 cases had no
      findings of sexual intercourse but they complained of forcible sexual intercourse
      and found no sign of sexual intercourse. Most of the alleged victims of rape were
      nulliparous 87.12% and parous was only 12.87%. 430 (61.51%) cases of reported
      victims who were students of schools and colleges were not considered as rape
      cases considering their victim's history of love affairs, leaving home secretly
      with their lovers, living with them for many days. Gang rape was not so common
      (4.29% of raped cases) in our study. Age groups, their occupations, living areas,
      time of arrival for medico-legal examination have been studied. Most of the cases
      were students (61.51%). A few numbers of victims were subjected to gang rape.
      Examination and reporting the cases have been discussed.

PMID- 20046169
TI  - Morphological study of extrauterine length of the fallopian tube at different age
      group in Bangladeshi people.
AB  - This cross sectional descriptive study was done to see the length of the right &
      left fallopian tube in Bangladeshi female and to increase the knowledge regarding
      variational anatomy in our country. Sixty post mortem specimens containing
      uterus, uterine tube, ureter and surrounding structures were collected by non
      random or purposive sampling technique from cadavers of different age groups and
      fixed in 10% formol saline solution. This study was carried out in the department
      of Anatomy of Mymensingh Medical College, Mymensingh from July 2006 to June 2007.
      Gross and fine dissection was carried out to study the length of fallopian tube
      (right & left). In this study our findings were compared with those of the
      standard text books. Maximum length of fallopian tube was found in middle age
      group (B = 13 to 45 years). It is about 9.19 cm in right side and 8.82 cm in left
      side. It is also important to note that more kinking was observed in middle age
      group.

PMID- 20046170
TI  - Evaluation of simple hematological screen for early diagnosis of neonatal sepsis.
AB  - This prospective study was undertaken in Dhaka Shishu Hospital from 15th March
      2005 to 15th October 2006 to evaluate the role of simple hematological test for
      early diagnosis of neonatal sepsis. Eighty suspected cases of septicaemia
      admitted in neonatal ward of Dhaka Shishu Hospital were included in this study.
      Patients those who had history of perinatal asphyxia, infant of diabetic mother,
      congenital cyanotic heart disease etc. were excluded from the study. Thirty
      neonates without sign symptoms of septicaemia admitted for other causes like
      jaundice, feeding problems etc. were taken as a control group. After taking
      informed consent data were collected in structured questionnaire. Following
      laboratory investigations like total WBC count, differential count, absolute
      neutrophil count, band cell count, platelet count, CRP, blood culture were done.
      Micro-ESR was done as bed side test. Immature and total neutrophil ratio (I/T
      ratio) detected from total neutrophil and band form count. Patients with positive
      blood culture were categorized as definite sepsis. Patients with negative blood
      culture but abnormal hematological report suggestive of sepsis were categorized
      as probable sepsis. Those who had no signs of sepsis were categorized as control
      group. Absolute neutrophil count (ANC) had low sensitivity (13%) but Micro-ESR,
      CRP, I/T ratio, platelet count had moderately high sensitivity and specificity.
      These simple hematological screen are useful marker for early diagnosis of
      neonatal sepsis.

PMID- 20046171
TI  - Effects of therapeutic modalities on patients with post stroke shoulder pain.
AB  - A randomized clinical trial was conducted to find out the effects of physical
      modalities transcutaneous electrical nerve stimulation (TENS) and ultrasonic
      therapy (UST) on the patients with post stroke shoulder pain in the Department of
      Physical Medicine & Rehabilitation & Department of Neurology, Bangabandhu Sheikh
      Mujib Medical University (BSMMU) from 1st July 2006 to 31st December 2006. In
      that period a total of 750 stroke patients attended the stroke clinic of the
      Department of Neurology, BSMMU, of which 150(20%) patients presented with post
      stroke shoulder pain. Among the patients with post stroke shoulder pain, 45(6%)
      patients were included in the study. The aim of the study was to find out the
      improvement with proper and timely physical therapy and to study the comparative
      efficacy of TENS or UST therapy on shoulder pain in stroke patients. Results of
      this study showed that most of the patients were elderly and maximum number of
      patients (86.66%) was diagnosed as adhesive capsulitis. In each group, pain
      reduction and increase of muscle strength was same, TENS showed better
      improvement of muscle strength. There was complete recovery of tenderness by both
      TENS and UST. Significant improvement was observed after treatment in each group
      except in active internal rotation in UST group. But in comparison between two
      groups, Group A (TENS) showed statistically significant better improvement in all
      planes of pain free range of motion than Group B except active abduction which
      was better improved in group B (UST) and in case of passive abduction, passive
      external rotation and passive extension, TENS had better effect than UST. It may
      be concluded that TENS and UST both are effective but TENS may be safer and
      superior to ultrasonic therapy (UST) in the treatment of the patients with post
      stroke shoulder pain.

PMID- 20046172
TI  - Ethical issues in surgical intervention in medical college hospitals.
AB  - The aim of this study was to investigate the ethical issues of the patients
      selected for surgical interventions. A total of 105 patients were selected
      consecutively on the basis of defined criteria at the Department of Surgery and
      the Department of Gynecology & Obstetrics of Sir Salimullah Medical College
      Mitford Hospital, Dhaka from March 2007 to November 2007. Results showed that
      76.19% of the patients were found to be literate and 23.81% were illiterate. In
      profession, 53.34% of the patients were found to be involved in household works,
      16.19% were service holders, 12.38% were businessmen, 9.52% were cultivators,
      5.71% were students and the rest were day laborers. Nearly 60.0% of the patients
      had no monthly income. Most of the patients were adults of age ranges from 16-70
      years. Results about ethical issues showed that 52.38% of the patients had no
      knowledge about surgical treatment of their diseases prior to operation, 26.67%
      had poor knowledge and 20.95% had sufficient knowledge. Adequate counseling
      earlier to surgical intervention were ensured for 11.43% (n=12) patients only.
      Rest of the patients (88.57%) was not experienced counseling before operation.
      Nearly 81.0% of the patients did not understand about their treatment by surgical
      intervention. About 94.0% of the patients and their close relatives had no
      knowledge about informed consent and its importance as well as procedure of
      obtains but they sign it just before operation. Around 91.0% of the informed
      consents were not taken in presence of any witness. In postoperative counseling,
      88.57% of the patients had not counseled. Nearly 66.0% of the patients did not
      satisfy about their treatment. In conclusion, truth-telling through counseling
      and informed consent were not found to be exercised properly in most of the
      patients undergoing surgical interventions in medical college hospitals.

PMID- 20046173
TI  - Procedural sedation in children for magnetic resonance imaging--comparison
      between ketamine diazepam combination with midazolam fentanyl combination.
AB  - A deeper level of sedation by an anaesthesiologist is requirement for magnetic
      resonance imaging (MRI) in paediatric populations and sedation of children is
      different from sedation of adults. The purpose of the study was to compare the
      efficacy, safety, tolerability and cost effectiveness of ketamine, diazepam
      combination to midazolam, fentanyl combination for sedation of children during
      MRI. One hundred twenty children of both sex, age between 1-10 years, American
      Society of Anesthesiologist (ASA) physical status I and II were distributed into
      two groups. Group A (n=60) were sedated with 1.5 mg/kg body weight ketamine and
      0.1 mg/kg body weight diazepam intravenously. Group B (n=60) were sedated with
      midazolam 0.05 mg/kg bodyweight and fentanyl 1 microg/kg body weight
      intravenously. Both groups showed satisfactory sedating condition for MRI.
      Incidences of side effects of drug regimens during sedation and recovery were
      recorded in both groups; those were transient and minor inconveniences. Pulse,
      blood pressure and respiration were within normal range in both groups. Mean
      procedure time was almost same in both groups and mean recovery time was more in
      group A than group B and the difference was statistically significant (p<0.05).
      Every child of both groups was discharged to home. Sedation regimen of group B
      found 5 times more costly than group A. Both the regimens were found safe and
      effective for paediatric sedation during MRI but ketamine, diazepam combination
      found more cost effective which, is a considerable matter in Bangladesh.

PMID- 20046174
TI  - Subtypes of dissociative (conversion) disorder in two tertiary hospitals in
      Bangladesh.
AB  - Dissociative (conversion) disorders are common among the patients attending in
      and out patients of Psychiatry Department of tertiary hospitals in Bangladesh.
      This study was done to see the subtypes of dissociative (conversion) disorder
      according to International Classification of Diseases, Tenth Revision (ICD-10).
      This is a descriptive, cross sectional study done on 100 consecutive patients
      from the Departments of Psychiatry, Bangabandhu Sheikh Mujib Medical University
      (BSMMU), Dhaka and Dhaka Medical College Hospital (DMCH). Study period was July
      2005 to June 2006. Among the patients of dissociative (conversion) disorder,
      mixed dissociative (conversion) disorder was found highest 34%, followed by
      dissociative convulsion 33%, dissociative motor disorders 19%, dissociative
      anaesthesia and sensory loss 5%, dissociative amnesia 4%, dissociative fugue 3%.
      However, the researcher did not find any multiple personality disorder which is
      relatively common in North America. This finding reflected that there are
      differences in prevalence of sub types of dissociative disorders in Bangladesh
      and Western countries.

PMID- 20046175
TI  - Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the
      treatment of tinea versicolor: a randomized clinical trial.
AB  - Tinea (pityriasis) versicolor is a superficial fungal infection and one of the
      most commonly found pigmentary disorders of skin caused by the yeast Malassezia.
      Multiple topical as well as systemic therapies are available for treatment.
      Systemic therapies are used for extensive disease, frequent relapse or where
      topical agents have failed. The aim that translates the rationale of the study
      was to compare the efficacy, safety, tolerability and cost effectiveness of
      single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment
      of tinea versicolor. A clinical study was done to compare the efficacy of single
      dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the
      treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years)
      were selected for the study during the period of June 2007 to May 2008 in the
      department of Dermatology of three different hospitals in Bangladesh. Cases
      having with extensive involvement, diagnosed clinically and confirmed by wood's
      lamp and KOH microscopy were taken. Patients were randomly allocated into equal
      groups. Group A was given single dose 400 mg itraconazole and Group B was given 7
      day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were
      included in the study. The mean age of group A was 32.37+/-9 years and in group B
      33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months
      and 2.76+/-2 months in group B. In group A clinical responders was found cure
      22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%)
      and improvement 4(13.33%). The measure at the End point (EP1) equals to 90%
      response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%).
      (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows
      91.66% response. Both single dose and 7 day daily dose of itraconazole can be
      effective in the treatment of tinea versicolor with extensive involvement but
      single dose appears to be better for improving compliance and decreasing the cost
      of treatment.

PMID- 20046176
TI  - Experience in laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is accepted as the procedure of choice for gallstone
      diseases but like all other procedure it is also not free from unwanted events.
      In this study, the authors have analyzed their experience in laparoscopic
      cholecystectomy (LC) and its complications and their management. Amongst the
      total 4957 laparoscopic cholecystectomy (LC) performed by the authors between
      April 1995 to May 2005 the male, female ratio was 1:5.6 (744 and 4213).
      15.33%(760) of LC were carried out for the patients with acute cholecystitis. The
      age ranged from 9 years to 98 years. Mean operating time was 37 minutes (7 m to
      187 m). Average hospital stay was 2.23 days (20 h to 7d). Peri-cholecystic
      adhesions including cholecysto-enteric fistulae and acute inflammation were the
      main reason for difficult dissection. This could be anticipated from the history
      of recurrent attack, high fever, severe pain and thick walled gall bladder (GB)
      on ultrasonography (USG). The main per-operative problem the authors came across
      was hemorrhage 5.2%(258), iatrogenic perforation of the gallbladder 15.12%(755)
      and common bile duct (CBD) injuries 0.12%(7). Conversion to open procedure was
      necessary in 0.68%(36) cases, most commonly due to obscure anatomy as a result of
      chronic inflammatory adhesions 0.56%(28), the other reasons for conversion were
      to deal with the CBD injury 0.04%(2), cholecysto-colic fistula 0.02%(1),
      unsuspected malignancy 0.06%(3) and uncontrolled bleeding 0.04%(2). The
      postoperative complications were port site infection and stitch granuloma
      0.75%(37), bile leakage 0.08%(4), hemorrhage 0.06%(3), sub-hepatic abscess
      0.02%(1), peritonitis due to gut perforation 0.04%(2) and retained bile duct
      stones 0.06%(3). Two deaths were due to septicemia resulting from gut
      perforation. Laparoscopic cholecystectomy is a safe procedure in the hands of a
      surgeon with adequate exposure to open surgery and properly oriented in minimally
      invasive surgery. Complications can be reduced to minimum if meticulous principle
      of dissection is followed. The unwanted events can mostly be managed
      laparoscopically without conversion. But decision for conversion should be taken
      early if there is any confusion and thus mortality and morbidity could be
      minimized.

PMID- 20046177
TI  - Prevalence and health-care seeking pattern of patients with functional diarrhoea
      in an urban community of Bangladesh.
AB  - Continuous or recurrent passage of loose (mushy) or watery stools without pain
      constitutes functional diarrhea (FD). This study aimed to find out the prevalence
      of functional diarrhea and health care seeking pattern in an urban community of
      Bangladesh. In this population-based cross-sectional survey 1503 (>/=15 years)
      subjects from an urban community were personally interviewed in a home setting
      using a valid questionnaire based on internationally accepted Rome II criteria.
      For this study, FD was defined as passage of loose or mushy or watery stools more
      than a quarter (25%) of time without abdominal pain in the last one-year.
      Significance value was assessed using Chi-squared test and the level of
      significance was denoted as P value of 0.05 or less. A response rate of 97.2%
      yielded 1503 questionnaires for analysis. Forty-four subjects were excluded from
      the study for various illness and denial to participate in the study. A lower
      prevalence of FD (3.7%) was found in our study population in comparison to
      irritable bowel syndrome (7.7%) by Rome II definition. Prevalence was found more
      in males than females (4.4% vs.3.3%) and in the 45-54 years' group. Approximately
      26(47.3%) FD subjects consulted a physician in the past one-year with a slightly
      higher rate of women consulters (57.7%) (P=0.181). The main predictor for health
      care seeking was presence of multiple symptoms. The prevalence of FD is low in
      our community in comparison to irritable bowel syndrome. A good number of FD
      patients do not seek medical care for their illness.

PMID- 20046178
TI  - Histopathological spectrum of childhood nephrotic syndrome in different hospitals
      of Dhaka City.
AB  - Nephrotic syndrome in children is a clinical manifestation of different
      histopathological subtypes of glomerulopathies. There is a paucity of studies
      about the histopathological spectrum of childhood nephrotic syndrome in our
      country. A cross sectional study was carried out from July 2005 to June 2007 with
      the aim to see the pattern of glomerulonephritis in renal biopsy samples of
      childhood nephrotic syndrome along with types of immune deposition. Thirty
      paediatric patients with their relevant clinical history and renal biopsy were
      evaluated by light microscopic study and by immunofluorescence microscopy.
      Mesangial-proliferative glomerulonephritis was found to be the most common cause
      of nephrotic syndrome followed by minimal change disease in the present study.
      IgM was found to be the most frequent form of immune deposition in case of
      mesangial proliferative glomerulonephritis.

PMID- 20046179
TI  - Malarigen malaria Pf/Pv antigen rapid test: a simple and effective tool for
      diagnosis of malaria in the far-flung hilly areas of Bangladesh.
AB  - Microscopic visualization of malarial parasites on thick and/or thin film is
      considered as "Gold Standard" for diagnosis of malaria. But it needs skilled
      microscopist as well as good laboratory set up, which are scarce in Chittagong
      Hill Tracts (CHT) in Bangladesh. A study was carried out to evaluate the efficacy
      of a newly introduced Rapid Diagnostic Test (RDT) device based on
      immunochromatographic test (ICT) format, for malarial parasite. This study was
      carried out at Balipara, a remote village 64 km away from Bandarban Hill District
      headquarters, during January 2007 to September 2007. A total 271 patients who
      reported to Sickbay of 37 Rifle Battalion, Balipara were tested by MALARIAGEN
      MALARIA Pf/Pv Antigen Rapid Test kit on the spot. Thick & thin blood films were
      prepared and stained by laboratory technician at the sick bay, properly labeled,
      preserved and sent to pathologist working at Armed Forces Medical College, Dhaka
      Cantonment, Dhaka for microscopy. Three (1.11%) cases were excluded as control
      band of RDT were negative or test band appeared after long incubation. Six
      (2.22%) were excluded for poor quality of staining blood film. Among 262 cases
      malarial parasites were detected in 74(28.24%). Of these 62(83.78%) were
      Plasmodium falciparum and 12(16.22%) were Plasmodium vivax. Parasite count ranged
      from 2500/muL to 527500/muL with mean 67400/muL (+/-93400). Among 262 cases,
      97(37.02%) were positive for malarial antigen(s) in RDT. Of these 74(76.29%) were
      P. falciparum and 23(23.71%) were P. vivax. Overall sensitivity and specificity
      of RDT for detection of malarial antigen(s) irrespective of their species were
      95.95% and 86.71% respectively with positive and negative predictive value 73% &
      98% respectively. Relative to microscopy, the device has shown sensitivity 94.6%
      and specificity 88.52% for detection of P. falciparum with positive and negative
      predictive value 72% and 98% respectively. The device sensitivity and specificity
      for detection of P. vivax were 100% and 93.1% with respective positive and
      negative predictive value 47% and 100%. Malariagen Malaria Pf/Pv Antigen Rapid
      Test (RDT) performs as a better sensor and discriminator of malarial parasites
      and their species and appears to be an acceptable tool for diagnosis of malaria
      in symptomatic patient.

PMID- 20046180
TI  - Histopathological changes in different stages of alopecia areata.
AB  - Alopecia areata is a common disorder affecting any of the hair bearing areas of
      the body. Most of the cases are diagnosed on the clinical ground only.
      Histopathological changes may help in the diagnosis in difficult cases. The
      present study was designed to observe the histopathologic changes of alopecia
      areata at different stages. Thirty consecutive patients suffering from alopecia
      areata were enrolled. Face to face interview was performed using a structured pre
      tested questionnaire. At the initial visit, one 4mm punch scalp biopsy specimen
      was taken from an area of hair loss. Biopsy specimens were sent in a test tube
      filled with formalin to the department of Pathology, Bangabandhu Sheikh Mujib
      Medical University (BSMMU) where tissue was processed, sectioned and slides were
      prepared. Haematoxylin and eosin stains were used. Aanagen hairs were decreased
      in all stages of alopecia areata. Telogen hairs increased in acute and chronic
      stages whereas catagen hairs increased markedly in sub-acute stage. Although
      miniaturized (atrophic) follicle was frequently found in chronic stage. It was
      absent in acute and sub-acute stages. Moderate to dense peribulbar infiltration
      of lymphocytes were observed in acute stage and mild to moderate infiltration in
      sub-acute stage. In chronic stage either no or mild infiltrations were observed.
      Peribulbar infiltration of eosinophils and macrophages were seen in all stages of
      alopecia areata. Alopecia areata can be diagnosed with some confidence, even when
      inflammatory infiltrate is absent, based on increased numbers of telogen hairs in
      the acute and chronic stages, increased miniaturized hairs in chronic stage and
      markedly increased catagen hairs in sub-acute stage.

PMID- 20046181
TI  - Role of immunochromatographic test for rapid diagnosis of malaria.
AB  - The study was conducted to compare among the different diagnostic procedures for
      malaria in the department of Microbiology, Mymensingh Medical College, Mymensingh
      during the period from July 2005 to June 2006. In this study a total of 98
      malaria patients were included as cases. Another 30 age and sex matched healthy
      people were included as controls. Blood sample from each of the case and control
      was collected and examined for malarial parasite by microscopic examination of
      peripheral blood film. Subsequently antigen and antibody were detected by immuno
      chromatographic test (ICT). Out of 98 clinically suspected cases 59(60.20%) were
      positive for malarial parasite by microscopic examination of peripheral blood
      film, 57(58.16%) were positive by ICT for antigen and 58(59.19%) were positive by
      ICT for antibody. Sensitivity and specificity of ICT for antigen were 93.22% and
      94.87% respectively. For antibody, sensitivity and specificity were 89.83% and
      87.17% respectively. From this study, sensitivity and specificity of ICT for
      malaria was found quite satisfactory, so it is suggested that ICT for malaria
      could be an alternative to peripheral blood film for the diagnosis of malaria
      where parasite could not be detected in peripheral blood film.

PMID- 20046182
TI  - Application of positron emission tomography in physical medicine.
AB  - Positron emission tomography (PET) is widely used in the fields of clinical and
      basic medicine. The PET device utilizes coincidence logic to detect annihilation
      photons emitted from positrons and estimates physiological functions of human
      organs in vivo. Radiopharmaceutical 18F- fluorodeoxyglucose (FDG), an analogue of
      glucose, is trapped metabolically in cells after being administered into the
      body, and can be substantially used for evaluating physiological and biochemical
      functions in vivo. Here, we attempted to describe the basics of PET as well as to
      apply the technique together with 18F-FDG as a tracer for evaluating organ
      glucose metabolism induced by exercise. Three-dimensional (3D) FDG-PET was
      applied to normal volunteers who performed exercise to evaluate whole-body
      glucose metabolism. Regions of interest analysis were drawn on visually defined
      regions (i.e., lower limbs, thigh, liver, intestine, brain, heart, etc.) to
      determine radioactivity distribution. FDG-PET clearly showed the recruitment of
      energy resources from abdominal organs to lower limb skeletal muscles to balance
      energy expenditures. The results suggested that 3D FDG-PET can be applied as an
      imaging tool to physical medicine.

PMID- 20046183
TI  - A 12 years old boy with carcinoma rectum.
AB  - Primary gastrointestinal malignancy constitutes approximately 2% of pediatric
      neoplasm and colorectal carcinoma is the second most common malignancy among
      them. This is one of the rarer diseases in children. Carcinoma of the rectum must
      be considered as a differential diagnosis in childhood if patient presents with
      per rectal bleeding in conjunction with abdominal pain & weight loss. In our
      article a 12 years old boy with Mucin secreting adenocarcinoma is being
      presented. The patient presented with incontinence of stool, with abdominal pain
      and history of swelling of left lower abdomen during defaecation. He got admitted
      in a district hospital for several times and USG of whole abdomen was done for
      several times but no abnormality was detected. Later on, by simple digital rectal
      examination (DRE) he was clinically diagnosed as a case of CA Rectum and
      eventually, the diagnosis was established by colonoscopy followed by biopsy.

PMID- 20046184
TI  - Sub arachnoid block for emergency cesarean section in a pituitary dwarf.
AB  - Anaesthesia for parturient patients with dwarfism is an uncommon problem faced by
      anaesthesiologists. There is an ongoing debate regarding general versus regional
      anaesthesia in these cases. In many centers there is lack of facilities for
      epidural or continuous epidural anaesthesia. A primiparous dwarf woman of 27
      years old having 124 cm height and 37 kg weight was admitted in Mymensingh
      Medical College Hospital for elective cesarean section due to cephalopelvic
      disproportion. She was diagnosed as a case of pituitary dwarf previously on
      antenatal checkup depending on both clinical and endocrine ground. After
      admission she suddenly developed respiratory distress with less foetal movement
      and presented in our department for emergency cesarean section. We have managed
      the case by sub-arachnoid block (SAB) using 7.5 mg (1.5 ml) of 0.5% heavy
      bupivacaine at a level of L3-L4 interspace having adequate level of block and
      analgesia. The case was managed successfully and uneventfully. In this
      presentation, the role of SAB and a management guideline has been highlighted.

PMID- 20046185
TI  - A neglected case of congenital pseudarthrosis of tibia.
AB  - Congenital pseudarthrosis of the tibia (CPT) is a rare malformation. It was first
      described by Hatzoecher in 1708. Treatment options of the congenital
      pseudarthrosis of tibia are variable and challenging. Various forms of bone
      grafts such as autologous iliac bone graft or free vascularised fibular graft,
      bracing, electrical stimulation, external fixators including Ilizarov technique
      and internal fixation with rods and plates are used. Here we represent a case of
      congenital pseudarthrosis of the tibia (CPT) of a 15 year-old boy, a shopkeeper
      hailing from Barhatta, Netrokona and diagnosed by history, clinical examination
      and x-ray. He was treated by Ilizarov technique and follow up was done for a
      period of 1 year. Complete union was achieved with correction of angulation and
      shortening.

PMID- 20046186
TI  - Fahr's disease: a very rare cause of epilepsy.
AB  - Fahr's disease, first described by Karl Theodor Fahr in 1930, refers to sporadic
      or familial idiopathic basal ganglia calcification that is associated with many
      neurological and psychiatric abnormalities, but may also be secondary to other
      diseases. Most cases present with extrapyramidal symptoms. But here we describe a
      case of Fahr's disease, who presented with complex partial seizure and behavioral
      abnormalities. On screening, the cause of seizure was found to be bilateral
      calcification of cerebellum, basal ganglia and thalamus, due to abnormal calcium
      and phosphate metabolism. A clinical diagnosis of complex-partial seizure with
      secondary generalization due to secondary Fahr's disease was done on the basis of
      clinical features, investigations, and exclusion of other causes of intracranial
      calcification.

PMID- 20046187
TI  - Back pain and vertebral compression: an unusual presentation of childhood acute
      lymphoblastic leukemia.
AB  - Junayet, a nine years and six months old boy was admitted to the hospital because
      of back pain and vertebral compression fractures. The boy had been well until two
      months earlier, when he began to have back pain after falling on his back along
      with occasional fever. The pain was intermittent initially but gradually it
      became constant. One month before admission, he fell again and the back pain
      became deteriorated. He was mildly pale, liver was palpable, skin survey revealed
      normal, BCG scar mark was present. He had bone pain, cervical lymphadenopathy and
      a tender swelling on the lumbusacral region. Two weeks before admission, the
      hematological findings were suggestive of leukemia of lymphoblastic type.
      Biochemical values were normal except high level of serum lactate dehydrogenase
      (LDH). Cerebrospinal fluid (CSF) examination was free of malignant cell. Skeletal
      survey showed diffuse osteopenia of the thoracic and lumber spine with multiple
      compression fracture of the vertebral bodies of D7, D8, D12 and L1, L3 and L5
      with increased disc space. Radiograph of the chest also showed diffuse osteopenia
      of ribs. Magnetic resonance (MRI) showed uniform signal intensity in the marrow
      throughout the spine with compressed fracture of the same vertebrae. Bone marrow
      morphology study and the cytochemistry of the aspirated marrow were consistent
      with acute lymphoblastic leukemia (ALL-L2). Then, he was started protocol based
      chemotherapy for induction of remission, consolidation, high dose methotrexate
      and maintenance therapy. Now, he is on regular follow up with repeated
      hematological and radiological examinations. Following six month of chemotherapy
      the boy was found with significant improvement of his physical, hematological and
      radiological abnormalities.

PMID- 20046188
TI  - Cutis laxa: a case report and an update.
AB  - Very few cases of Cutis Laxa are reported worldwide. This is the first case
      report of its kind from Bangladesh. A 10 year-old girl looking very aged was
      admitted in the paediatric ward of Dhaka Medical College with most striking skin
      feature. There was loosely hanging skin over the face which was inelastic, hyper
      extensible and which recoils slowly after stretching. She had downward slanting
      palpebral fissures, periorbital oedema, a broad flat nose with everted nostril,
      sagging cheeks, and large and soft ears. Skin biopsy showed fragmentation of the
      elastic tissue with collagen tissue in the dermis, which was suggestive of Cutis
      Laxa. Her chest x-ray showed hypertranslucent lung fields, prominence of
      pulmonary conus area and some ring like opacity near the lower zone with
      cardiomegaly, which is suggestive of corpulmonale with bronchiectasis. Her
      echocardiography showed dilated right atrium, ventricle and pulmonary artery
      which were suggestive of corpulmonale. All these confirmed the diagnosis.

PMID- 20046189
TI  - Cryptococcosis in organ transplantation.
AB  - Opportunistic infection is one of the important cause of graft dysfunction after
      organ transplantation. It usually occurs one year after post transplantation in a
      immunocompromised transplant recipient. Among the opportunistic infections fungal
      infection is important cause of graft dysfunction as well as increase morbidity
      and mortality of post transplant recipient. Cryptococcosis is the third most
      common invasive fungal infection in an organ transplant recipient next to
      Candidiasis and Aspergillosis. A 27 years young male is known case of live
      related renal allograft recipient on immunosuppression for last one and half
      years. Patient was admitted with irregular fever, severe headache, nausea and
      vomiting in the department of Nephrology on July 2007. After admission patient
      was thoroughly evaluated and clinically found features of meningitis. Subsequent
      investigation report revealed swollen of 3rd ventricle on CT scan brain and
      growth of Cryptococcus in CSF culture and diagnosis was made post renal
      transplant cryptococcal meningitis. Treatment was given with Injection
      Amphotericin B along with immunosuppression and other supportive measured. But
      inspite of treatment, within few days after diagnosis patient was underwent coma
      and died. In conclusion, cryptococcal meningitis is a serious invasive fungal
      infection in post transplant immunocompromised recipient and responsible for
      graft lose and increase morbidity of the transplant patients.

PMID- 20046190
TI  - Swine flu: a new emerging disease.
AB  - Swine flu is an important zoonotic disease that has been recognized as an
      important global health problem by any one of several types of swine influenza
      virus or swine-origin influenza virus. Due to its increasing incidence in many
      countries of the world and occurrence of several large outbreaks in present year,
      it is a burning issue nowadays. It is thought to be a mutation--more
      specifically, a reassortment of four known strains of influenza A virus subtype
      H1N1. Swine influenza virus is common throughout pig populations worldwide.
      Transmission of the virus from pigs to humans is not common and does not always
      lead to human influenza, often resulting only in the production of antibodies in
      the blood. Due to variability of clinical features and limited availability of
      laboratory facilities, the disease remains largely under-reported. Early and
      specific diagnosis is important to ensure a favourable outcome. In this paper we
      attempted to explore history, classification, transmission, sign symptoms,
      diagnosis and prevention of swine flu as a critical review to provide some new
      upgrade regarding this devastating pandemic disease.

PMID- 20046191
TI  - Retirement and relevant contemplation.
AB  - Retirement literally means withdrawing from the service. The retirement age
      varies from country to country, generally between 55 and 70 years. There are many
      effects of retirement upon retirees. The physical and mental health may be
      disrupted or decline or may remain unaffected. Early retirement have an increased
      mortality than those who retired lately. Mandatory retirement is applicable to
      certain occupation like military personnel and airline pilot. Life after
      retirement from service may have many options like retired community, charities,
      tourism, and care for grand children or devote to a hobby or sports. The
      responsibilities of the Government, family and society are the key for the
      betterment of retired persons. Staying healthy, maintaining social support,
      spiritual life, good finance and making daily routine prevent stress after
      retirement.

PMID- 20046192
TI  - Regular physical exercise: way to healthy life.
AB  - Any bodily activity or movement that enhances and maintains overall health and
      physical fitness is called physical exercise. Habit of regular physical exercise
      has got numerous benefits. Exercise is of various types such as aerobic exercise,
      anaerobic exercise and flexibility exercise. Aerobic exercise moves the large
      muscle groups with alternate contraction and relaxation, forces to deep breath,
      heart to pump more blood with adequate tissue oxygenation. It is also called
      cardiovascular exercise. Examples of aerobic exercise are walking, running,
      jogging, swimming etc. In anaerobic exercise, there is forceful contraction of
      muscle with stretching, usually mechanically aided and help to build up muscle
      strength and muscle bulk. Examples are weight lifting, pulling, pushing,
      sprinting etc. Flexibility exercise is one type of stretching exercise to improve
      the movements of muscles, joints and ligaments. Walking is a good example of
      aerobic exercise, easy to perform, safe, effective, does not require any training
      or equipment and less chance of injury. Regular 30 minutes brisk walking in the
      morning with 150 minutes per week is a good exercise. Regular exercise improves
      the cardiovascular status, reduces the risk of cardiac disease, high blood
      pressure and cerebrovascular disease. It reduces body weight, improves insulin
      sensitivity, helps in glycemic control, prevents obesity and diabetes mellitus.
      It is helpful for relieving anxiety, stress, brings a sense of well being and
      overall physical fitness. Global trend is mechanization, labor savings and
      leading to epidemic of long term chronic diseases like diabetes mellitus,
      cardiovascular diseases etc. All efforts should be made to create public
      awareness promoting physical activity, physically demanding recreational pursuits
      and providing adequate facilities.

PMID- 20046193
TI  - Centenary of Brodmann's map--conception and fate.
AB  - Rarely in the history of neuroscience has a single illustration been as
      influential as the cytoarchitectonic map of the human brain published by
      Korbinian Brodmann in his monograph from 1909. The map presents the segregation
      of the cerebral cortex into 43 areas, as visible in cell body-stained
      histological sections. More importantly, Brodmann provided a comparative
      neuroanatomical approach and discussed ontogenetic and pathological aspects as
      well as structural-functional correlations. One hundred years later, a large
      number of neuroscientists still use Brodmann's map for localizing neuroimaging
      data obtained in the living human brain.

PMID- 20046194
TI  - The memory function of sleep.
AB  - Sleep has been identified as a state that optimizes the consolidation of newly
      acquired information in memory, depending on the specific conditions of learning
      and the timing of sleep. Consolidation during sleep promotes both quantitative
      and qualitative changes of memory representations. Through specific patterns of
      neuromodulatory activity and electric field potential oscillations, slow-wave
      sleep (SWS) and rapid eye movement (REM) sleep support system consolidation and
      synaptic consolidation, respectively. During SWS, slow oscillations, spindles and
      ripples - at minimum cholinergic activity - coordinate the re-activation and
      redistribution of hippocampus-dependent memories to neocortical sites, whereas
      during REM sleep, local increases in plasticity-related immediate-early gene
      activity - at high cholinergic and theta activity - might favour the subsequent
      synaptic consolidation of memories in the cortex.

PMID- 20046196
TI  - If you have the science, we have the journal!

PMID- 20046195
TI  - Epididymal tissue in the dilated portion of a dysgenetic kidney with an
      ipsilateral seminal vesicle cyst and ectopic ureteral insertion.

PMID- 20046199
TI  - Mobilizing forces--CD4+ helper T cells script adaptive immunity.

PMID- 20046200
TI  - Connective tissue diseases: A nonsurgical therapy for Dupuytren disease.

PMID- 20046201
TI  - Therapy: Optimum therapy in septic arthritis: to cut or not to cut?

PMID- 20046202
TI  - Therapy: Hydroxychloroquine in SLE: old drug, new perspectives.

PMID- 20046203
TI  - Psychology: Emotional disclosure in RA: does it work?

PMID- 20046204
TI  - Update on gout: new therapeutic strategies and options.
AB  - Gout, a disease recognized since antiquity, has increased in prevalence in recent
      years and the clinical profile of this disease has become increasingly complex,
      owing to large numbers of cases with iatrogenic factors, multiple comorbidities,
      advanced age, and hyperuricemia and arthritis refractory to treatment. In this
      Review, key advances in gout research made during the past decade are summarized.
      Revised strategies for safe and effective employment of dietary measures and
      pharmacologic treatments for active gouty arthritis, prevention of gout flares
      and urate lowering are also reviewed, with an emphasis on dosing of colchicine
      and allopurinol, and the evidence-based approach to systemic glucocorticosteroid
      treatment of acute gout. Also discussed are new and emerging treatments for gout
      and hyperuricemia, and the potential influence of dual energy CT imaging on
      treatment. In this context, the therapeutic role of febuxostat, and clinical
      development of pegylated uricase urate-lowering therapy and interleukin 1
      antagonism for gouty inflammation are reviewed. Collectively, novel approaches
      will hopefully lead to improved management of hyperuricemia and gout, and also to
      improvements in patient-centered outcomes, even for those who have previously
      failed to respond to treatment.

PMID- 20046207
TI  - Personality and fear responses during conditioning: Beyond extraversion.
AB  - The personality domain of introversion-extraversion has been theorized to be
      associated with the strength of fear conditioning, but the literature on this
      topic has been equivocal. Furthermore, except for extraversion and neuroticism,
      relationships of the other Big Five personality domains with fear response
      acquisition have not been explored. In the current study, multi-level modeling
      was used to examine the relationships of facets of the Big 5 domains to fear
      response acquisition. Participants were 217 police and firefighter trainees who
      completed the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992)
      and a fear conditioning task as part of a larger study. Results indicated that
      several facets of extraversion have opposing associations with fear response
      acquisition of an electrodermal response- possibly contributing to the mixed
      results in the literature. Additionally, facets of other Big Five domains were
      found to be associated with fear response acquisition.

PMID- 20046205
TI  - Type I interferons: crucial participants in disease amplification in
      autoimmunity.
AB  - A significant body of data implicates the type I interferon (IFN) pathway in the
      pathogenesis of autoimmune rheumatic diseases. In these disorders, a self
      reinforcing cycle of IFN production can contribute to immunopathology through
      multiple mechanisms. Type I IFN cytokines are pleiotropic in their effects,
      mediating antiviral and antitumor activities, and possess numerous
      immunomodulatory functions for both the innate and adaptive immune responses. A
      key principle of the type I IFN system is rapid induction and amplification of
      the signaling pathway, which generates a feed-forward loop of IFN production,
      ensuring that a vigorous antiviral immune response is mounted. Although such feed
      forward pathways are highly adaptive when it comes to rapid and effective virus
      eradication, this amplification can be maladaptive in immune responses directed
      against host tissues. Such feed-forward loops, however, create special
      opportunities for therapy.

PMID- 20046208
TI  - Computational Modeling of Inclusion Complexes of beta-Cyclodextrin with
      enantiomers of Salsolinol, N-Methyl-Salsolinol, and 1-Benzyl
      Tetrahydroisoquinoline.
AB  - Capillary electrophoresis with beta-CD as a chiral selector has successfully
      separated the two enantiomers of salsolinol, N-methyl-salsolinol, and 1-benzyl
      tetrahydroisoquinoline. The migration times of each enantiomer in capillary
      electrophoresis reflect the stability of their beta-CD inclusion complexes. This
      paper reports a computational modeling study of the inclusion complexes of beta
      cyclodextrin (beta-CD) with salsolinol, N-methyl-salsolinol, and 1-benzyl
      tetrahydroisoquinoline by using PM3 (Parametric Method 3) semi-empirical
      molecular orbital calculations and the ONIOM hybrid method. Two types of the
      inclusion complexes, cis- and trans-orientations, are considered for each
      enantiomer of the guest molecules, salsolinol, N-methyl-salsolinol, and 1-benzyl
      tetrahydroisoquinoline. In the cis-orientation, the nitrogen in the salsolinol, N
      methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline points toward the
      secondary hydroxyls of the beta-CD, while in the trans-orientation, the nitrogen
      in salsolinol, N-methyl-salsolinol, and 1-benzyl-tetrahydroisoquinoline points
      toward the primary hydroxyls of the beta-CD. We found that the stabilization
      energies of these inclusion complexes from these PM3 and ONIOM different methods
      correlate very well with the migration order deduced from the study of capillary
      electrophoretic separation.

PMID- 20046206
TI  - Mechanical signals as anabolic agents in bone.
AB  - Aging and a sedentary lifestyle conspire to reduce bone quantity and quality,
      decrease muscle mass and strength, and undermine postural stability, culminating
      in an elevated risk of skeletal fracture. Concurrently, a marked reduction in the
      available bone-marrow-derived population of mesenchymal stem cells (MSCs)
      jeopardizes the regenerative potential that is critical to recovery from
      musculoskeletal injury and disease. A potential way to combat the deterioration
      involves harnessing the sensitivity of bone to mechanical signals, which is
      crucial in defining, maintaining and recovering bone mass. To effectively utilize
      mechanical signals in the clinic as a non-drug-based intervention for
      osteoporosis, it is essential to identify the components of the mechanical
      challenge that are critical to the anabolic process. Large, intense challenges to
      the skeleton are generally presumed to be the most osteogenic, but brief exposure
      to mechanical signals of high frequency and extremely low intensity, several
      orders of magnitude below those that arise during strenuous activity, have been
      shown to provide a significant anabolic stimulus to bone. Along with positively
      influencing osteoblast and osteocyte activity, these low-magnitude mechanical
      signals bias MSC differentiation towards osteoblastogenesis and away from
      adipogenesis. Mechanical targeting of the bone marrow stem-cell pool might,
      therefore, represent a novel, drug-free means of slowing the age-related decline
      of the musculoskeletal system.

PMID- 20046209
TI  - Neural Activation in Women in Response to Masculinized Male Faces: Mediation by
      Hormones and Psychosexual Factors.
AB  - Women's preference for masculine faces varies with hormonal state,
      sociosexuality, and relationship status, but the underlying mechanisms are poorly
      understood. We hypothesized that hormones and psychosexual factors
      (sociosexuality, sexual inhibition/excitation) mediate the perception and
      evaluation of male faces thereby influencing women's preferences. We used fMRI to
      measure brain activity in twelve women as they evaluated pictures of male faces
      (half 30% masculinized, half 30% feminized). Participants were heterosexual
      women, age 23-28, who were not in a committed relationship and not using hormonal
      contraception. Women were tested during both the follicular and luteal phase of
      their menstrual cycle. We found five brain regions related to face and risk
      processing that responded more to the masculinized than to the feminized faces,
      including the superior temporal gyrus, precentral gyrus, posterior cingulate
      cortex, inferior parietal lobule, and anterior cingulate cortex. Increased
      activation in the anterior cingulate cortex, specifically, may indicate that
      women perceive masculinized faces to be both more risky and more attractive. We
      did not see any areas that were more strongly activated by feminized faces.
      Levels of activation were influenced by hormonal and psychosexual factors. The
      patterns of hormonally and psychosexually mediated neural activation observed may
      offer insight into the cognitive processes underlying women's partner
      preferences.

PMID- 20046210
TI  - Brief Report: Toward Refinement of a Predictive Behavioral Profile for Treatment
      Outcome in Children with Autism.
AB  - Previously researchers identified a behavioral profile that predicted treatment
      response of children with autism to a specific behavioral intervention, Pivotal
      Response Training (PRT). This preliminary investigation sought to refine this
      profile by obtaining six participants matching the original nonresponder profile
      on all but one of the profile behaviors (toy contact or avoidance) and then
      assessing their response to PRT. In addition, participants received a course of
      Discrete Trial Training (DTT) to determine whether the profile predicted child
      response to this intervention. Altering the original profile behavior of toy
      contact led to improved response to PRT while, altering the profile behavior of
      high avoidance had little impact on treatment response, and the profile was not
      predictive of response to DTT.

PMID- 20046211
TI  - Liquid Chromatographic Determination of NSC 737664 (ABT-888: an Inhibitor of
      Poly(ADP-ribose) Polymerase (PARP)) in Plasma and Urine in a Phase 0 Clinical
      Trial.
AB  - A gradient reversed-phase high performance liquid chromatographic method was
      developed for determining NSC 737664 (2-[(2R)-2-methylpyrrolidin-2-yl]-1H
      benzimidazole-4-carboxamide; ABT-888) in human plasma and urine. Chromatographic
      separation used a mobile phase composed of 0.1% formic acid in water and 0.1%
      formic acid in acetonitrile, and a C18 column (150 mm * 4.6 mm, 5u). Quantitation
      was performed using UV detection at 300 nm. Chromatographic peak identity was
      confirmed using positive-ion electrospray ionization mass spectrometry. The
      method was shown to be specific, accurate and reproducible, and thereby
      appropriate for monitoring plasma and urine levels of the agent in support of a
      phase 0 clinical study.

PMID- 20046212
TI  - Multiple simultaneous detection of Harmful Algal Blooms (HABs) through a high
      throughput bead array technology, with potential use in phytoplankton community
      analysis.
AB  - As an alternative to traditional, morphology-based methods, molecular techniques
      can provide detection of multiple species within the HAB community and, more
      widely, the phytoplankton community in a rapid, accurate and simultaneous
      qualitative analysis. These methods require detailed knowledge of the molecular
      diversity within taxa in order to design efficient specific primers and specific
      probes able to avoid cross-reaction with non-target sequences. Isolates from
      Florida coastal communities were sequence-analyzed and compared with the GenBank
      database. Almost 44% of the genotypes obtained did not match any sequence in
      GenBank, showing the existence of a large and still unexplored biodiversity among
      taxa. Based on these results and on the GenBank database, we designed 14 species
      specific probes and 4 sets of specific primers. Multiple simultaneous detection
      was achieved with a bead array method based on the use of a flow cytometer and
      color-coded microspheres, which are conjugated to the developed probes. Following
      a parallel double PCR amplification, which employed universal primers in a
      singleplex reaction and a set of species-specific primers in multiplex, detection
      was performed in a cost effective and highly specific analysis. This multi-format
      assay, which required less than 4 h to complete from sample collection, can be
      expanded according to need. Up to 100 different species can be identified
      simultaneously in a single sample, which allows for additional use of this method
      in community analyses extended to all phytoplankton species. Our initial field
      trials, which were based on the 14 species-specific probes, showed the co
      existence and dominance of two or more species of Karenia during toxic blooms in
      Florida waters.

PMID- 20046213
TI  - Personality, Menopausal Symptoms, and Physical Activity Outcomes in Middle-Aged
      Women.
AB  - The menopausal transition is characterized by increased reporting of various
      symptoms, however, little is known about what underlies individual differences in
      their reporting. The present study examined the contribution of personality
      factors to the reporting of menopausal symptoms in the context of a 4-month
      randomized controlled exercise trial. Symptomatic middle-aged women (N = 164 M
      age = 49.9, SD = 3.6) completed measures of menopausal symptoms, personality,
      physical activity, fitness and body composition assessment at the beginning and
      end of a 4-month randomized controlled trial involving walking and yoga. After
      controlling for baseline values, psychological symptoms at the end of the trial
      were associated with trait anxiety (beta = .47, p < .001) and changes in fitness
      (beta = -.20, p < .01); vasomotor symptoms with optimism (beta = -.18, p < .05)
      and changes in fitness (beta = -.15, p = .053); and sexual symptoms were
      associated with changes in fitness (beta = -.16, p < .05). Personality
      characteristics partially explain symptom reports during menopause however
      improvements in physical parameters such as fitness may reduce reported
      symptomatology.

PMID- 20046214
TI  - Incorporation of hexafluorobutyne into furans or phenols via reaction with
      iron(0) carbene or vinylketene complexes.
AB  - Reaction of iron(0) carbene complexes with hexafluorobut-2-yne produces 3,4
      bis(trifluoromethylated)furans in a process that is favored for electron rich
      carbenes. No traces of furannulation or benzannulation are observed with Group 6
      Fischer carbenes. Reaction of hexafluorobut-2-yne with a vinylketene iron(0)
      complex gives a 2,3-bis-trifluoromethylated phenol.

PMID- 20046215
TI  - Redox Dynamics of Mixed Metal (Mn, Cr, and Fe) Ultrafine Particles.
AB  - The impact of particle composition on metal oxidation state, and on changes in
      oxidation state with simulated atmospheric aging, are investigated experimentally
      in flame-generated nanoparticles containing Mn, Cr, and Fe. The results
      demonstrate that the initial fraction of Cr(VI) within the particles decreases
      with increasing total metal concentration in the flame. In contrast, the initial
      Mn oxidation state was only partly controlled by metal loading, suggesting the
      importance of other factors. Two reaction pathways, one reductive and one
      oxidative, were found to be operating simultaneously during simulated atmospheric
      aging. The oxidative pathway depended upon the presence of simulated sunlight and
      O(3), whereas the reductive pathway occurred in the presence of simulated
      sunlight alone. The reductive pathway appears to be rapid but transient, allowing
      the oxidative pathway to dominate with longer aging times, i.e. greater than ~8
      hours. The presence of Mn within the particles enhanced the importance of the
      oxidative pathway, leading to more net Cr oxidation during aging implying that Mn
      can mediate oxidation by removal of electrons from other particulate metals.

PMID- 20046216
TI  - Linguistic Summarization of Video for Fall Detection Using Voxel Person and Fuzzy
      Logic.
AB  - In this paper, we present a method for recognizing human activity from linguistic
      summarizations of temporal fuzzy inference curves representing the states of a
      three-dimensional object called voxel person. A hierarchy of fuzzy logic is used,
      where the output from each level is summarized and fed into the next level. We
      present a two level model for fall detection. The first level infers the states
      of the person at each image. The second level operates on linguistic
      summarizations of voxel person's states and inference regarding activity is
      performed. The rules used for fall detection were designed under the supervision
      of nurses to ensure that they reflect the manner in which elders perform these
      activities. The proposed framework is extremely flexible. Rules can be modified,
      added, or removed, allowing for per-resident customization based on knowledge
      about their cognitive and physical ability.

PMID- 20046217
TI  - Within-category VOT affects recovery from "lexical" garden paths: Evidence
      against phoneme-level inhibition.
AB  - Spoken word recognition shows gradient sensitivity to within-category voice onset
      time (VOT), as predicted by several current models of spoken word recognition,
      including TRACE (McClelland & Elman, Cognitive Psychology, 1986). It remains
      unclear, however, whether this sensitivity is short-lived or whether it persists
      over multiple syllables. VOT continua were synthesized for pairs of words like
      barricade and parakeet, which differ in the voicing of their initial phoneme, but
      otherwise overlap for at least four phonemes, creating an opportunity for
      "lexical garden-paths" when listeners encounter the phonemic information
      consistent with only one member of the pair. Simulations established that phoneme
      level inhibition in TRACE eliminates sensitivity to VOT too rapidly to influence
      recovery. However, in two Visual World experiments, look-contingent and response
      contingent analyses demonstrated effects of word initial VOT on lexical garden
      path recovery. These results are inconsistent with inhibition at the phoneme
      level and support models of spoken word recognition in which sub-phonetic detail
      is preserved throughout the processing system.

PMID- 20046218
TI  - Natural Mentoring and Psychosocial Outcomes among Older Youth Transitioning From
      Foster Care.

PMID- 20046219
TI  - Structure and Continuity of Intellectual Development in Early Childhood.
AB  - We evaluated over 200 participants semiannually from 12 to 48 months of age on
      measures of intellectual (Bayley Scales, Stanford-Binet Scale) and verbal
      (MacArthur-Bates Inventory, Peabody Picture Vocabulary Test) status. Structural
      equation modeling and hierarchical linear (growth curve) analyses were applied to
      address the nature of development and individual differences during this time.
      Structural analyses showed a strong and robust simplex model from infancy to the
      preschool period, with no evidence of qualitative reorganizations or
      discontinuities. Growth-curve modeling revealed significant associations between
      level factors across the early and later measures of cognition, providing further
      evidence of continuity; the growth trajectory from the Bayley through 24 months
      predicted growth in a nonverbal factor, but not in a verbal factor. Altogether,
      the findings reveal continuous and stable development in intellectual function
      from late infancy through the preschool years. Additionally, the high level of
      continuity demonstrated across these ages was observed to be largely independent
      of growth in vocabulary.

PMID- 20046220
TI  - New evidence for rapid development of color-location binding in infants' visual
      short-term memory.
AB  - Change-detection tasks reveal that infants' ability to bind color to location in
      visual short-term memory (VSTM) develops rapidly: Seven-month-old infants, but
      not 6-month-old infants, detect that successive arrays of 3 objects are different
      if they contain the same colors in different locations (Oakes et al., 2006). Here
      we test a counterintuitive consequence of the hypothesis that six-month-old
      infants are unable to bind colors to locations: When comparing two successive
      stimulus arrays, these infants will often compare noncorresponding items, making
      it impossible for them to distinguish between identical arrays and nonidentical
      arrays. As a result, they will not show a preference for changing arrays over
      nonchanging arrays even when all of the items change. We tested this prediction
      by presenting 6- and 7-month-old infants (N = 36) with nonchanging displays of
      three items and changing displays in which all three items simultaneoulsy changed
      colors. As predicted, 7-month-old infants, but not 6-month-old infants, responded
      to the difference between these changing and nonchanging displays, providing
      additional evidence that the ability to bind colors to locations develops rapidly
      across this age range.

PMID- 20046221
TI  - Anthrax edema toxin inhibits Nox1-mediated formation of reactive oxygen species
      by colon epithelial cells.
AB  - One major route of intoxication by Bacillus anthracis (anthrax) spores is via
      their ingestion and subsequent uptake by the intestinal epithelium. Anthrax edema
      toxin (ETx) is an adenylate cyclase that causes persistent elevation of cAMP in
      intoxicated cells. NADPH oxidase enzymes (Nox1-Nox5, Duox1 and 2) generate
      reactive oxygen species (ROS) as components of the host innate immune response to
      bacteria, including Nox1 in gastrointestinal epithelial tissues. We show that ETx
      effectively inhibits ROS formation by Nox1 in HT-29 colon epithelial cells. This
      inhibition requires the PKA-mediated phosphorylation of the Nox1-regulatory
      component, NoxA1, and the subsequent binding of 14-3-3zeta. Inhibition of Nox1
      mediated ROS formation in the gut epithelium may be a mechanism used by B.
      anthracis to circumvent the innate immune response.

PMID- 20046222
TI  - Welfare Reform in the mid-2000s: How African-American and Hispanic Families in
      Three Cities are Faring.
AB  - This article reports on a sample of 538 African American and Hispanic women who
      were receiving TANF in 1999, 416 of whom left the program by 2005. The Hispanic
      women consisted of a Mexican-origin group and a second group that was primarily
      Puerto Rican and Dominican. Combining the experiences of the employed and the non
      employed welfare leavers, we find at best a modest decline in the average poverty
      rate among African American welfare leavers between 1999 and 2005. Mexican-origin
      and other Hispanic leavers showed larger average declines in poverty. Among just
      the welfare leavers who were employed in 2005, the averages for women in all
      racial-ethnic groups showed increases in household income and declines in
      poverty. Among those who were not employed, African-Americans had experienced a
      decline in household income and were further below the poverty line than in 1999,
      whereas Hispanic women had experienced modest declines or slight increases in
      their household incomes.

PMID- 20046223
TI  - Towards a Biocompatible, Biodegradable Copolymer Incorporating Electroactive
      Oligothiophene Units.
AB  - As part of an ongoing effort to develop biocompatible, biodegradable conducting
      polymers, we report here the synthesis and characterization of a novel copolymer,
      5,5"'bishydroxymethyl-3,3"'-dimethyl-2,2':5',2":5",2"'-quaterthiophene-co-adipic
      acid polyester (QAPE). This system was designed so as to incorporate alternating
      electroactive quaterthiophene units and biodegradable ester units into one
      macromolecular framework, while allowing for facile preparation of the polymer
      via a polycondensation reaction. In agreement with the design expectations, the
      ester groups were found to be incorporated into the polymer between the
      quaterthiophene subunits, as inferred from standard chemical and spectroscopic
      analyses. QAPE exhibited redox activity as detected by cyclic voltammetry and a
      new red-shifted absorption peak upon doping, providing support for the notion
      that the quaterthiophene units maintain electroactivity after incorporation into
      the QAPE polymer framework. The degradation, likely through surface erosion, of
      this polymer in the presence of cholesterol esterase was confirmed by the
      detection of a fluorescence signal at wavelengths corresponding to the
      quaterthiophene subunit and comparisons to appropriate controls. In vitro
      cytocompatability studies, carried out over 48 h, indicate that the QAPE polymer
      is nontoxic to Schwann cells.

PMID- 20046224
TI  - Shared Features Dominate Semantic Richness Effects for Concrete Concepts.
AB  - When asked to list semantic features for concrete concepts, participants list
      many features for some concepts and few for others. Concepts with many semantic
      features are processed faster in lexical and semantic decision tasks (Pexman,
      Holyk, & Monfils, 2003; Pexman, Lupker, & Hino, 2002). Using both lexical and
      concreteness decision tasks, we provided further insight into these number-of
      features (NoF) effects. We began by replicating the effect using a larger and
      better controlled set of items. We then investigated the relationship between NoF
      and feature distinctiveness and found that features shared by numerous concrete
      concepts such as <has four legs> facilitate decisions to a greater extent than do
      distinctive features such as <moos>. Finally, we showed that NoF effects are
      carried by shared visual form and surface, encyclopedic, tactile, and taste
      knowledge. We propose a decision-making account of these results, rather than one
      based on the computation of word meaning.

PMID- 20046225
TI  - "They Are the Reason I Come to Work": The Meaning of Resident-Staff Relationships
      in Assisted Living.
AB  - This article aims to provide understanding of how direct care workers (DCWs) in
      assisted living facilities (ALFs) interpret their relationships with residents
      and to identify factors that influence the development, maintenance, quality, and
      meaning of these relationships. Qualitative methods were used to study two ALFs
      (35 and 75 beds) sequentially over seven months. Researchers conducted in-depth
      interviews with 5 administrative staff and 38 DCWs and conducted 243 hours of
      participant observation during a total of 99 visits. Data were analyzed using a
      grounded theory approach. Results showed that the emotional aspect of caregiving
      provides meaning to DCWs through both the satisfaction inherent in relationships
      and through the effect of relationships on care outcomes. Within the context of
      the wider community and society, multiple individual- and facility-level factors
      influence DCW strategies to create and manage relationships and carry out care
      tasks and ultimately find meaning in their work. These meanings affect their job
      satisfaction and retention.

PMID- 20046226
TI  - Structural Analysis and Mechanical Characterization of Hyaluronic Acid-Based
      Doubly Cross-Linked Networks.
AB  - We have created a new class of hyaluronic acid (HA)-based hydrogel materials with
      HA hydrogel particles (HGPs) embedded in and covalently cross-linked to a
      secondary network. HA HGPs with an average diameter of ~900 nm and narrow
      particle size distribution were synthesized using a refined reverse micelle
      polymerization technique. The average mesh size of the HGPs was estimated to be
      approximately 5.5 to 7.0 nm by a protein uptake experiment. Sodium periodate
      oxidation not only introduced aldehyde groups to the particles but also reduced
      the average particle size. The aldehyde groups generated were used as reactive
      handles for subsequent cross-linking with an HA derivative containing hydrazide
      groups. The resulting macroscopic gels contain two distinct hierarchical networks
      (doubly cross-linked networks, DXNs): one within individual particles and another
      among different particles. Bulk gels (BGs) formed by direct mixing of HA
      derivatives with mutually reactive groups were included for comparison. The
      hydrogel microstructures were collectively characterized by microscopy and
      neutron scattering techniques. Their viscoelasticity was quantified at low
      frequencies (0.1-10 Hz) using a controlled stress rheometer and at high
      frequencies (up to 200 Hz) with a home-built torsional wave apparatus. Both BGs
      and DXNs are stable elastic gels that become stiffer at higher frequencies. The
      HA-based DXN offers unique structural hierarchy and mechanical properties that
      are suitable for soft tissue regeneration.

PMID- 20046227
TI  - Photochemical reaction of 9-nitro-substituted anthracene-like molecules 9-methyl
      10-nitroanthracene and 12-methyl-7-nitrobenz[a]anthracene.

PMID- 20046228
TI  - Light-Induced Toxic Effects of Tamoxifen: A Chemotherapeutic and Chemopreventive
      Agent.
AB  - Tamoxifen is a powerful drug used to treat breast cancer patients, and more than
      500,000 women in the U. S. are being treated with this drug. In our study,
      tamoxifen is found to be photomutagenic in Salmonella typhimurium TA102 at
      concentrations as low as 0.08 muM and reaches maximum photomutagenicity at 0.4
      muM under a light dose equivalent to 20 min sunlight. These concentrations are
      comparable to the plasma tamoxifen concentration of 0.4 to 3 muM for patients
      undergoing tamoxifen therapy. The toxicity seems to be the result of DNA damage
      and/or lipid peroxidation caused by light irradiation of tamoxifen. The DNA
      damage caused by irradiation of PhiX174 DNA in the presence of tamoxifen appears
      to be formation of DNA-tamoxifen covalent adducts, not single strand/double
      strand cleavages, and there is no oxygen involvement. This is confirmed by EPR
      experiments that carbon-centerd radicals are formed by light irradiation of
      tamoxifen and there is no singlet oxygen formation. Although superoxide radical
      is formed, it is not involved in DNA damage.

PMID- 20046229
TI  - Fat-storing multilocular cells expressing CCR5 increase in the thymus with
      advancing age: potential role for CCR5 ligands on the differentiation and
      migration of preadipocytes.
AB  - Age-associated thymic involution is characterized by decreased thymopoiesis,
      adipocyte deposition and changes in the expression of various thymic
      microenvironmental factors. In this work, we characterized the distribution of
      fat-storing cells within the aging thymus. We found an increase of unilocular
      adipocytes, ERTR7(+) and CCR5(+ )fat-storing multilocular cells in the thymic
      septa and parenchymal regions, thus suggesting that mesenchymal cells could be
      immigrating and differentiating in the aging thymus. We verified that the
      expression of CCR5 and its ligands, CCL3, CCL4 and CCL5, were increased in the
      thymus with age. Hypothesizing that the increased expression of chemokines and
      the CCR5 receptor may play a role in adipocyte recruitment and/or differentiation
      within the aging thymus, we examined the potential role for CCR5 signaling on
      adipocyte physiology using 3T3-L1 pre-adipocyte cell line. Increased expression
      of the adipocyte differentiation markers, PPARgamma2 and aP2 in 3T3-L1 cells was
      observed under treatment with CCR5 ligands. Moreover, 3T3-L1 cells demonstrated
      an ability to migrate in vitro in response to CCR5 ligands. We believe that the
      increased presence of fat-storing cells expressing CCR5 within the aging thymus
      strongly suggests that these cells may be an active component of the thymic
      stromal cell compartment in the physiology of thymic aging. Moreover, we found
      that adipocyte differentiation appear to be influenced by the proinflammatory
      chemokines, CCL3, CCL4 and CCL5.

PMID- 20046230
TI  - Comparison between single antiplatelet therapy and combination of antiplatelet
      and anticoagulation therapy for secondary prevention in ischemic stroke patients
      with antiphospholipid syndrome.
AB  - Satisfactory results have not yet been obtained in therapy for secondary
      prevention in ischemic stroke patients with antiphospholipid syndrome (APS). We
      therefore compared single antiplatelet therapy and a combination of antiplatelet
      and anticoagulation therapy for secondary prevention in ischemic stroke patients
      with APS.The subjects were 20 ischemic stroke patients with antiphospholipid
      antibody, 13 with primary antiphospholipid syndrome and 7 with SLE-related
      antiphospholipid syndrome. Diagnosis of APS was based on the 2006 Sydney
      criteria. Eligible patients were randomly assigned to either single antiplatelet
      therapy (aspirin 100 mg) or a combination of antiplatelet and anticoagulation
      therapy (target INR: 2.0-3.0; mean 2.4+/-0.3) for the secondary prevention of
      stroke according to a double-blind protocol. There was no significant difference
      between the two groups in age, gender, NIH Stroke Scale on admission, mRS at
      discharge, or rate of hypertension, diabetes mellitus, hyperlipidemia, or cardiac
      disease. We obtained Kaplan-Meier survival curves for each treatment. The primary
      outcome was the occurrence of stroke. The mean follow-up time was 3.9+/-2.0
      years. The cumulative incidence of stroke in patients with single antiplatelet
      treatment was statistically significantly higher than that in patients receiving
      the combination of antiplatelet and anticoagulation therapy (log-rank test, p
      value=0.026). The incidence of hemorrhagic complications was similar in the two
      groups. The recent APASS study did not show any difference in effectiveness for
      secondary prevention between single antiplatelet (aspirin) and single
      anticoagulant (warfarin) therapy. Our results indicate that combination therapy
      may be more effective in APS-related ischemic stroke.

PMID- 20046231
TI  - The Diels-Alder-reaction with inverse-electron-demand, a very efficient versatile
      click-reaction concept for proper ligation of variable molecular partners.
AB  - The ligation of active pharmaceutical ingredients (API) for working with image
      processing systems in diagnostics (MRT) attracts increasing notice and scientific
      interest. The Diels-Alder ligation Reaction with inverse electron demand
      (DAR(inv)) turns out to be an appropriate candidate. The DAR(inv) is
      characterized by a specific distribution of electrons of the diene and the
      corresponding dienophile counterpart. Whereas the reactants in the classical
      Diels-Alder Reaction feature electron-rich diene and electron-poor dienophile
      compounds, the DAR(inv) exhibits exactly the opposite distribution of electrons.
      Substituents with pushing electrones increase and, with pulling electrons reduce
      the electron density of the dienes as used in the DAR(inv).We report here that
      the DAR(inv) is an efficient route for coupling of multifunctional molecules like
      active peptides, re-formulated drugs or small molecules like the alkyalting agent
      temozolomide (TMZ). This is an example of our contribution to the "Click
      chemistry" technology. In this case TMZ is ligated by DAR(inv) as a cargo to
      transporter molecules facilitating the passage across the cell membranes into
      cells and subsequently into subcellular components like the cell nucleus by using
      address molecules. With such constructs we achieved high local concentrations at
      the desired target site of pharmacological action. The DAR(inv) ligation was
      carried out using the combination of several technologies, namely: the organic
      chemistry and the solid phase peptide synthesis which can produce 'tailored'
      solutions for questions not solely restricted to the medical diagnostics or
      therapy, but also result in functionalizations of various surfaces qualified
      amongst others also for array development.We like to acquaint you with the
      DAR(inv) and we like to exemplify that all ligation products were generated after
      a rapid and complete reaction in organic solutions at room temperature, in high
      purity, but also, hurdles and difficulties on the way to the TMZ-BioShuttle
      conjugate should be mentioned.With this report we would like to stimulate
      scientists working with the focus on "Click chemistry" to intensify research with
      this expanding DAR(inv )able to open the door for new solutions inconceivable so
      far.

PMID- 20046233
TI  - Factors associated with false-positive emergency medical services triage for
      percutaneous coronary intervention.
AB  - BACKGROUND: In 2005, Orange County California Emergency Medical Services (EMS)
      initiated a field 12-lead program to minimize time to emergency percutaneous
      coronary intervention (PCI) for field-identified acute myocardial infarction
      (MI). As the program matured, "false-positive" (defined as no PCI or coronary
      artery occlusion upon PCI) field MI activations have been identified as a problem
      for the program. OBJECTIVES: To identify potentially correctable factors
      associated with false-positive EMS triage to PCI centers. METHODS: This was a
      retrospective, outcome study of EMS 12-lead cases from February 2006 to June
      2007. The study system exclusively used cardiac monitor internal interpretation
      algorithms indicating an acute myocardial infarction as the basis for triage.
      Indicators and variables were defined prior to the study. Data, including
      outcome, was from the Orange County EMS database, which included copies of 12
      lead ECGs used for field triage. Negative odds ratios (OR) of less than 1.0 for
      positive PCI were the statistical measure of interest. RESULTS: Five hundred
      forty-eight patients were triaged from the field for PCI. We excluded 19 cases
      from the study because of death prior to PCI, refusal of PCI, and co-morbid
      illness (sepsis, altered consciousness) that precluded PCI. Three hundred ninety
      three (74.3%) patients had PCI with significant coronary lesions found. False
      positive field triages were associated with underlying cardiac rhythm of sinus
      tachycardia [OR = 0.38 (95% CI 0.23, 0.62)]; atrial fibrillation [OR = 0.43 (95%
      CI = 0.20, 0.94)]; an ECG lead not recorded [OR = 0.39 (95% CI = 0.20, 0.76)];
      poor ECG baseline [OR = 0.59 (95% CI = 0.25, 1.37)]; One of three brands of
      monitors used in the field [OR = 0.35 (95% CI = 0.21, 0.59)]; and female gender
      [OR = 0.50 (95% CI = 0.34, 0.75)]. Age was not associated with false-positive
      triage as determined by ordinal regression (p=1.00). CONCLUSION: For the urban
      suburban EMS field 12-lead program studied, age was not associated with false
      positive triage. It was unexpected that female gender was associated with false
      positive triage. False-positive triage from the field was associated with poor
      ECG acquisition, underlying rhythms of atrial fibrillation and sinus tachycardia,
      and one brand of 12-lead monitor.

PMID- 20046232
TI  - Ultra-low microcurrent in the management of diabetes mellitus, hypertension and
      chronic wounds: report of twelve cases and discussion of mechanism of action.
AB  - Oxidative stress plays a major role in the pathogenesis of both types of diabetes
      mellitus and cardiovascular diseases including hypertension. The low levels of
      antioxidants accompanied by raised levels of markers of free radical damage play
      a major role in delaying wound healing. Ultra-low microcurrent presumably has an
      antioxidant effect, and it was shown to accelerate wound healing. The purpose of
      the study is to investigate the efficacy of ultra-low microcurrent delivered by
      the Electro Pressure Regeneration Therapy (EPRT) device (EPRT Technologies-USA,
      Simi Valley, CA) in the management of diabetes, hypertension and chronic wounds.
      The EPRT device is an electrical device that sends a pulsating stream of
      electrons in a relatively low concentration throughout the body. The device is
      noninvasive and delivers electrical currents that mimic the endogenous electric
      energy of the human body. It is a rechargeable battery-operated device that
      delivers a direct current (maximum of 3 milliAmperes) of one polarity for 11.5
      minutes, which then switched to the opposite polarity for another 11.5 minutes.
      The resulting cycle time is approximately 23min or 0.000732 Hz and delivers a
      square wave bipolar current with a voltage ranging from 5V up to a maximum of 40
      V. The device produces a current range of 3 mA down to 100 nA. Twelve patients
      with long standing diabetes, hypertension and unhealed wounds were treated with
      EPRT. The patients were treated approximately for 3.5 h/day/5 days a week.
      Assessment of ulcer was based on scale used by National Pressure Ulcer Advisory
      Panel Consensus Development Conference. Patients were followed-up with daily
      measurement of blood pressure and blood glucose level, and their requirement for
      medications was recorded. Treatment continued from 2-4 months according to their
      response. Results showed that diabetes mellitus and hypertension were well
      controlled after using this device, and their wounds were markedly healed (30
      100%). The patients either reduced their medication or completely stopped after
      the course of treatment. No side effects were reported. The mechanism of action
      was discussed.

PMID- 20046234
TI  - International disaster medical sciences fellowship: model curriculum and key
      considerations for establishment of an innovative international educational
      program.
AB  - As recent events highlight, a global requirement exists for evidence-based
      training in the emerging field of Disaster Medicine. The following is an example
      of an International Disaster Medical Sciences Fellowship created to fill this
      need. We provide here a program description, including educational goals and
      objectives and a model core curriculum based on current evidence-based
      literature. In addition, we describe the administrative process to establish the
      fellowship. Information about this innovative educational program is valuable to
      international Disaster Medicine scholars, as well as U.S. institutions seeking to
      establish formal training in Disaster Medical Sciences.

PMID- 20046235
TI  - CAL/ACEP Joins CAL/AAEM and UC Irvine in Sponsoring the Western Journal of
      Emergency Medicine.

PMID- 20046236
TI  - Boarder Patrol: A Reform Policy for America's Paralyzed Emergency Departments.

PMID- 20046237
TI  - Promoting International Emergency Medicine through WestJEM.

PMID- 20046238
TI  - Introducing a Clinical Practice Guideline Using Early CT in the Diagnosis of
      Scaphoid and Other Fractures.
AB  - OBJECTIVE: We developed and implemented clinical practice guideline (CPG) using
      computerized tomography (CT) as the initial imaging method in the emergency
      department management of scaphoid fractures. We hypothesized that this CPG would
      decrease unnecessary immobilization and lead to earlier return to work. METHODS:
      This observational study evaluated implementation of our CPG, which incorporated
      early wrist CT in patients with "clinical scaphoid fracture": a mechanism of
      injury consistent with scaphoid fracture, anatomical snuff box tenderness, and
      normal initial plain x-rays. Outcome measures were the final diagnosis as
      determined by orthopaedic review of the clinical and imaging data. Patient
      outcomes included time to return to work and patient satisfaction as determined
      by telephone interview at ten days. RESULTS: Eighty patients completed the study
      protocol in a regional emergency department. In this patient population CT
      detected 28 fractures in 25 patients, including six scaphoid fractures, five
      triquetral fractures, four radius fractures, and 13 other related fractures.
      Fifty-three patients had normal CT. Eight of these patients had significant
      ongoing pain at follow up and had an MRI, with only two bone bruises identified.
      The patients with normal CTs avoided prolonged immobilization (mean time in
      plaster 2.7 days) and had no or minimal time off work (mean 1.6 days). Patient
      satisfaction was an average 4.2/5. CONCLUSION: This CPG resulted in rapid and
      accurate management of patients with suspected occult scaphoid injury, minimized
      unnecessary immobilization and was acceptable to patients.

PMID- 20046239
TI  - Crowding and delivery of healthcare in emergency departments: the European
      perspective.
AB  - Emergency department (ED) crowding is a multifactorial problem, resulting in
      increased ED waiting times, decreased patient satisfaction and deleterious domino
      effects on the entire hospital. Although difficult to define and once limited to
      anecdotal evidence, crowding is receiving more attention as attempts are made to
      quantify the problem objectively. It is a worldwide phenomenon with regional
      influences, as exemplified when analyzing the problem in Europe compared to that
      of the United States. In both regions, an aging population, limited hospital
      resources, staff shortages and delayed ancillary services are key contributors;
      however, because the structure of healthcare differs from country to country,
      varying influences affect the issue of crowding. The approach to healthcare
      delivery as a right of all people, as opposed to a free market commodity, depends
      on governmental organization and appropriation of funds. Thus, public funding
      directly influences potential crowding factors, such as number of hospital beds,
      community care facilities, and staffing. Ultimately ED crowding is a universal
      problem with distinctly regional root causes; thus, any approach to address the
      problem must be tailored to regional influences.

PMID- 20046240
TI  - Paramedics' ability to perform drug calculations.
AB  - BACKGROUND: The ability to perform drug calculations accurately is imperative to
      patient safety. Research into paramedics' drug calculation abilities was first
      published in 2000 and for nurses' abilities the research dates back to the late
      1930s. Yet, there have been no studies investigating an undergraduate paramedic
      student's ability to perform drug or basic mathematical calculations. The
      objective of this study was to review the literature and determine the ability of
      undergraduate and qualified paramedics to perform drug calculations. METHODS: A
      search of the prehospital-related electronic databases was undertaken using the
      Ovid and EMBASE systems available through the Monash University Library.
      Databases searched included the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, CINAHL, JSTOR, EMBASE and Google Scholar, from their
      beginning until the end of August 2009. We reviewed references from articles
      retrieved. RESULTS: The electronic database search located 1,154 articles for
      review. Six additional articles were identified from reference lists of retrieved
      articles. Of these, 59 were considered relevant. After reviewing the 59 articles
      only three met the inclusion criteria. All articles noted some level of
      mathematical deficiencies amongst their subjects. CONCLUSIONS: This study
      identified only three articles. Results from these limited studies indicate a
      significant lack of mathematical proficiency amongst the paramedics sampled. A
      need exists to identify if undergraduate paramedic students are capable of
      performing the required drug calculations in a non-clinical setting.

PMID- 20046241
TI  - Lead toxicity resulting from chronic ingestion of opium.
AB  - A 32-year-old man presented to the emergency department (ED) with lower abdominal
      pain and constipation. He related chronic ingestion of large amounts of opium.
      Physical examination showed mild abdominal tenderness and gingival discoloration.
      Diagnostic studies showed a mild hypochromic, microcytic anemia with basophilic
      stippling of the red blood cells. Abdominal imaging showed no intra-abdominal
      pathology. A diagnosis of lead toxicity was confirmed through serum lead levels.
      The patient was put on chelation therapy and his signs and symptoms started to
      resolve. As a comprehensive search for other sources of lead was unsuccessful,
      opium adulterants were considered as the culprit. Chemical analysis of the opium
      confirmed this. Contaminated drugs have been reported as a source of exposure to
      toxins such as arsenic or lead. While other reports deal with patients from
      clinics, this report illustrates lead toxicity from ingestion of contaminated
      opium in the ED.

PMID- 20046242
TI  - Thyroid gland hematoma after blunt neck trauma.
AB  - Hemorrhage of a previously normal thyroid gland as a result of blunt trauma is a
      very rare condition. We report a case of blunt trauma that caused acute
      hemorrhage into the thyroid gland and presented with hoarseness. The diagnosis of
      thyroid gland hematoma was made with a combination of fiberoptic laryngoscopy,
      cervical computed tomography, and carotid angiography. The patient was treated
      conservatively, had a favorable course without further complications, and was
      discharged four days after admission.

PMID- 20046243
TI  - Chilaiditi's Syndrome.

PMID- 20046244
TI  - Wound botulism in injection drug users: time to antitoxin correlates with
      intensive care unit length of stay.
AB  - OBJECTIVES: We sought to identify factors associated with need for mechanical
      ventilation (MV), length of intensive care unit (ICU) stay, length of hospital
      stay, and poor outcome in injection drug users (IDUs) with wound botulism (WB).
      METHODS: This is a retrospective review of WB patients admitted between 1991
      2005. IDUs were included if they had symptoms of WB and diagnostic confirmation.
      Primary outcome variables were the need for MV, length of ICU stay, length of
      hospital stay, hospital-related complications, and death. RESULTS: Twenty-nine
      patients met inclusion criteria. Twenty-two (76%) admitted to heroin use only and
      seven (24%) admitted to heroin and methamphetamine use. Chief complaints on
      initial presentation included visual changes, 13 (45%); weakness, nine (31%); and
      difficulty swallowing, seven (24%). Skin wounds were documented in 22 (76%).
      Twenty-one (72%) patients underwent mechanical ventilation (MV). Antitoxin (AT)
      was administered to 26 (90%) patients but only two received antitoxin in the
      emergency department (ED). The time from ED presentation to AT administration was
      associated with increased length of ICU stay (Regression coefficient = 2.5; 95%
      CI 0.45, 4.5). The time from ED presentation to wound drainage was also
      associated with increased length of ICU stay (Regression coefficient = 13.7; 95%
      CI = 2.3, 25.2). There was no relationship between time to antibiotic
      administration and length of ICU stay. CONCLUSION: MV and prolonged ICU stays are
      common in patients identified with WB. Early AT administration and wound drainage
      are recommended as these measures may decrease ICU length of stay.

PMID- 20046245
TI  - Terrain park injuries.
AB  - BACKGROUND: This study examined demographics, injury pattern, and hospital
      outcome in patients injured in winter resort terrain parks. METHODS: The study
      included patients >/=12 years of age who presented to a regional trauma center
      with an acute injury sustained at a winter resort. Emergency department (ED)
      research assistants collected patient injury and helmet use information using a
      prospectively designed questionnaire. ED and hospital data were obtained from
      trauma registry and hospital records. RESULTS: Seventy-two patients were injured
      in a terrain park, and 263 patients were injured on non-terrain park slopes.
      Patients injured in terrain parks were more likely to be male [68/72 (94%) vs.
      176/263 (67%), p<0.0001], younger in age [23 +/- 7 vs. 36 +/- 17, p<0.0001], live
      locally [47/72 (65%) vs. 124/263 (47%), p=0.006], use a snowboard [50/72 (69%)
      vs. 91/263 (35%), p<0.0001], hold a season pass [46/66 (70%) vs. 98/253 (39%),
      p<0.0001], and sustain an upper extremity injury [29/72 (40%) vs. 52/263 (20%),
      p<0.001] when compared to patients injured on non-terrain park slopes. There were
      no differences between the groups in terms of EMS transport to hospital, helmet
      use, admission rate, hospital length of stay, and patients requiring specialty
      consultation in the ED. CONCLUSIONS: Patients injured in terrain parks represent
      a unique demographic within winter resort patrons. Injury severity appears to be
      similar to those patients injured on non-terrain park slopes.

PMID- 20046246
TI  - The utility of bedside ultrasound in the detection of a ruptured globe in a
      porcine model.
AB  - BACKGROUND: Recent case reports have shown that ultrasonography can be used to
      diagnose ocular pathology in an emergency setting. Ultrasound may be especially
      useful when periorbital edema and pain interfere with the examination of the post
      traumatic eye. OBJECTIVE: This study evaluated the ability of emergency
      physicians to detect a ruptured globe in an ex-vivo porcine model. METHODS:
      Following a brief training lecture, 15 emergency medicine residents and 4
      emergency medicine attending physicians used ultrasonography to evaluate 18
      porcine eyes, randomized as normal, ruptured, or completely devoid of vitreous
      humor. The consequences of ultrasound applanation with this method were evaluated
      by measuring intraocular pressure changes with and without a 1mm clear plastic
      shield. RESULTS: Our study participants were able to identify abnormal eyes with
      a sensitivity of 79% (95% CI 73% to 84%) and a specificity of 51% (95% CI 41% to
      61%). Intraocular pressure increased 5% with ultrasound applanation, though with
      a 1mm thick plastic shield there was no measurable change. CONCLUSIONS:
      Ultrasound imaging may be a future modality to be used by trained emergency
      physicians to expedite the identification of a rupture globe, but it is unlikely
      to replace more definitive imaging techniques. The use of a clear plastic barrier
      in this porcine model prevents an increase in intra-ocular pressure without
      affecting image quality, and should be used in any future studies on this method.

PMID- 20046247
TI  - Cervical spine fracture in ankylosing spondylitis.

PMID- 20046248
TI  - Emergency department patients with psychiatric complaints return at higher rates
      than controls.
AB  - STUDY OBJECTIVE: At our 35,000 visit/year emergency department (ED), we studied
      whether patients presenting to the ED with psychiatric complaints were admitted
      to the hospital at a higher rate than non-psychiatric patients, and whether these
      patients had a higher rate of reevaluation in the ED within 30 days following the
      index visit. METHODS: We reviewed the electronic records of all ED patients
      receiving a psychiatric evaluation from January to February 2007 and compared
      these patients to 300 randomly selected patients presenting during the study
      period for non-psychiatric complaints. Patients were followed for 30 days, and
      admission rates and return visits were compared. RESULTS: Two hundred thirty-four
      patients presented to the ED and were evaluated for psychiatric complaints during
      the study period. Twenty-four point seven percent of psychiatric patients were
      admitted upon initial presentation versus 20.7% of non-psychiatric patients (p =
      0.258). Twenty-one percent of discharged psychiatric patients returned to the ED
      within 30 days versus 13.4% of discharged non-psychiatric patients (p=0.041).
      Patients returning to the ED within 30 days had a 17.1% versus 21.6% admission
      rate for the psychiatric and non-psychiatric groups, respectively (p=0.485).
      CONCLUSION: Patients presenting to this ED with psychiatric complaints were not
      admitted at a significantly higher rate than non-psychiatric patients. These
      psychiatric patients did, however, have a significantly higher return rate to the
      ED when compared to non-psychiatric patients.

PMID- 20046249
TI  - The clinical differentiation of cerebellar infarction from common vertigo
      syndromes.
AB  - This article summarizes the emergency department approach to diagnosing
      cerebellar infarction in the patient presenting with vertigo. Vertigo is defined
      and identification of a vertigo syndrome is discussed. The differentiation of
      common vertigo syndromes such as benign paroxysmal positional vertigo, Meniere's
      disease, migrainous vertigo, and vestibular neuritis is summarized. Confirmation
      of a peripheral vertigo syndrome substantially lowers the likelihood of
      cerebellar infarction, as do indicators of a peripheral disorder such as an
      abnormal head impulse test. Approximately 10% of patients with cerebellar
      infarction present with vertigo and no localizing neurologic deficits. The
      majority of these may have other signs of central vertigo, specifically direction
      changing nystagmus and severe ataxia.

PMID- 20046250
TI  - The back alley revisited: sepsis after attempted self-induced abortion.
AB  - While unsafe abortions have become rare in the United States, the practice
      persists. We present a 24-year-old female with a 21-week twin gestation who
      presented to the emergency department with complications of an attempted self
      induced abortion. Her complicated clinical course included sepsis,
      chorioamnionitis, fetal demise, and a total abdominal hysterectomy with bilateral
      salpingo-oophorectomy for complications of endomyometritis. We discuss unsafe
      abortions, risk factors, and the management of septic abortion. Prompt
      recognition by the emergency physician and aggressive management of septic
      abortion is critical to decreasing maternal morbidity and mortality.

PMID- 20046251
TI  - Non-traumatic urologic emergencies in men: a clinical review.
AB  - Although true urologic emergencies are extremely rare, they are a vital part of
      any emergency physician's (EP) knowledge base, as delays in treatment lead to
      permanent damage. The four urologic emergencies discussed are priapism,
      paraphimosis, testicular torsion, and Fournier's gangrene. An overview is given
      for each, including causes, pathophysiology, diagnosis, treatment, and new
      developments. The focus for priapism is on diagnosis and distinguishing high-flow
      from low-flow forms, as the latter requires emergent treatment. For paraphimosis,
      we describe various methods of relieving the stricture, from manual reduction to
      surgery in extreme cases. For testicular torsion, the most important factor in
      salvaging the testicle is decreasing time to treatment. This is accomplished
      through experience and understanding which signs and symptoms strongly suggest
      it, so that time-consuming tests are avoided. Lastly, Fournier's gangrene is
      potentially fatal. While aggressive medical and surgical therapy will improve
      chances of survival and outcome, it is vital for the emergency department (ED)
      physician to diagnose Fournier's. It often presents in the elderly,
      immunocompromised, or those with depressed mental status. The goal of this paper
      is to arm EPs with information to recognize urological emergencies and intervene
      quickly to preserve tissue, fertility, and life.

PMID- 20046252
TI  - Bilateral psoas abscess in the emergency department.
AB  - We present the case of a 45-year-old female who presented multiple times to the
      emergency department with acute low back pain and was subsequently diagnosed with
      bilateral psoas muscle abscess. Psoas abscess is an uncommon cause of acute low
      back pain that is associated with high morbidity and mortality. The onset of
      symptoms is frequently insidious and the clinical presentation vague. Proper
      diagnosis requires vigilance of the physician to recognize signs in the history
      and physical examination that are suggestive of a potentially serious spinal
      condition and initiate further workup. While most patients with acute low back
      pain have a benign etiology, this case report demonstrates the challenge of
      diagnosing a patient with bilateral psoas abscess who had few known risk factors
      and symptoms typical of mechanical low back pain.

PMID- 20046253
TI  - Lidocaine toxicity misinterpreted as a stroke.
AB  - For more than 50 years lidocaine has been used to treat ventricular arrhythmias.
      Neurologic dysfunction, manifested as a stroke, occurred acutely in an 87-year
      old woman after she had been administered repeated doses of lidocaine, a
      lidocaine infusion, then an intravenous amiodarone infusion for ventricular
      tachycardia. This was ultimately diagnosed as lidocaine toxicity with a serum
      lidocaine level of 7.9 mg/L (1.5-6.0 mg/L). We discuss lidocaine toxicity and
      risk factors leading to its development, which include particularly hepatic
      dysfunction, cardiac dysfunction, advanced age and other drug administration.

PMID- 20046255
TI  - Scrotal swelling after penetrating chest trauma.

PMID- 20046254
TI  - Molar pregnancy in the emergency department.
AB  - A 15-year-old female presented to the emergency department with complaints of
      vaginal bleeding. She was pale, anxious, cool and clammy with tachycardic,
      thready peripheral pulses and hemoglobin of 2.4g/dL. Her abdomen was gravid
      appearing, approximately early to mid-second trimester in size. Pelvic
      examination revealed 2 cm open cervical os with spontaneous discharge of blood,
      clots and a copious amount of champagne-colored grapelike spongy material. After
      2L boluses of normal saline and two units of crossmatched blood, patient was
      transported to the operating room. Surgical pathology confirmed a complete
      hydatidiform mole.

PMID- 20046256
TI  - Supraglottic laryngeal mass.

PMID- 20046257
TI  - Non-communicating hydrocephalus.

PMID- 20046258
TI  - Rhabdomyolysis-induced severe hyperkalemia.

PMID- 20046259
TI  - Ultrasound-confirmed frontal bone fracture.

PMID- 20046260
TI  - Non-traumatic Shoulder Dislocation.

PMID- 20046261
TI  - All that wheezes is not asthma.

PMID- 20046262
TI  - "Outside the institute there is a desert": the tenuous trajectories of medical
      research in interwar Australia.

PMID- 20046263
TI  - "Little, if at all, removed from the illiterate farrier or cow-leech": the
      English veterinary surgeon, c.1860-1885, and the campaign for veterinary reform.

PMID- 20046264
TI  - "Strike out boldly for the prizes that are available to you": medical emigration
      from Ireland 1860-1905.

PMID- 20046265
TI  - Empire and alternatives: Swietenia febrifuga and the Cinchona substitutes.

PMID- 20046266
TI  - The mind and stomach at war: stress and abdominal illness in Britain c.1939-1945.

PMID- 20046267
TI  - Postnatal steroids for chronic lung disease - a lesson learned.

PMID- 20046269
TI  - Neonatal herpes simplex virus infection: A devastating newborn pathogen.

PMID- 20046268
TI  - Early prophylactic inhaled beclomethasone in infants less than 1250 g for the
      prevention of chronic lung disease.
AB  - OBJECTIVE: Inflammation plays an important role in the development of chronic
      lung disease (CLD), which has become a major cause of morbidity in surviving
      infants less than 1250 g at birth. The authors hypothesized that the progression
      of this inflammation and, therefore, the establishment of CLD would be decreased
      with the use of early prophylactic inhaled corticosteroids. Short, and long term
      respiratory and neurodevelopmental outcomes were also examined. DESIGN: A double
      blind, randomized placebo controlled trial. SETTING: Level-III neonatal intensive
      care unit. POPULATION STUDIED: Sixty infants less than 1250 g at birth, diagnosed
      with respiratory distress syndrome and requiring ventilatory support at 72 h of
      age were enrolled in the study. INTERVENTION: Infants enrolled received either
      placebo or beclomethasone diproprionate by a metered dose inhaler, which was used
      in-line with the ventilator circuit while the infant was ventilated and then via
      a spacer until 28 days of age. RESULTS: Thirty infants were given beclomethasone
      and 30 were given placebo. There were two deaths in each group. Among the
      surviving infants, the frequency of moderate-to-severe CLD was 17% in each study
      group. Mean time to extubation was not different for beclomethasone compared with
      placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for
      intravenous corticosteroids was lower in the beclomethasone-treated group (RR
      0.67, 95% CI 0.43 to 1.04), although this difference was not statistically
      significant. The incidence of growth failure, infection and intraventricular
      hemmorhage did not differ between the two groups. Long term outcomes were not
      different with respect to the incidence of respiratory re-admissions, cerebral
      palsy, developmental delay, blindness or deafness. CONCLUSIONS: Early treatment
      with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or
      decrease the duration of mechanical ventilation. The decrease in intravenous
      corticosteroid use was not statistically significant. Long term outcome was not
      affected.

PMID- 20046270
TI  - Postnatal corticosteroids to treat or prevent chronic lung disease in preterm
      infants.
AB  - This statement is intended for health care professionals caring for neonates and
      young infants. The objectives of this statement are to review the short and long
      term effects of systemic and inhaled postnatal corticosteroids for the prevention
      or treatment of evolving or established chronic lung disease, and to make
      recommendations for the use of corticosteroids in infants with very low birth
      weight. The routine use of systemic dexamethasone for the prevention or treatment
      of chronic lung disease in infants with very low birth weight is not recommended.

PMID- 20046271
TI  - Winter safety tips for parents and children.

PMID- 20046272
TI  - Fever and irritability in a four-and-a-half-month-old infant.

PMID- 20046273
TI  - Is our vaccine supply secure?

PMID- 20046274
TI  - Ecstasy.

PMID- 20046275
TI  - Marijuana use in adolescence.
AB  - The prevalence of marijuana use by adolescents has fluctuated in recent decades,
      but, overall, has increased significantly. In a study of adolescent health status
      and risk behaviours among students in grades 7 to 12 in British Columbia, it was
      found that the patterns of marijuana use had changed, especially among early
      adolescents. An earlier age of onset of use and an increased frequency of use
      were noted. The present paper examines the clinical and psychosocial implications
      of early age of onset of marijuana use, and reports important differences in
      risky behaviours between users and nonusers. The prevailing attitude that
      marijuana is a 'safe, recreational' drug is challenged.

PMID- 20046276
TI  - Psychiatric treatment: A risk factor for obesity?
AB  - BACKGROUND: People with psychiatric diagnoses have increased physical health
      difficulties. OBJECTIVES: To examine the physical growth parameters documented in
      children receiving psychiatric treatment. METHODS: A chart review was performed
      on consecutive paediatric consultations in 1997 and 1998 on 34 children six to 12
      years of age admitted to an intermediate-stay psychiatric inpatient service.
      Growth parameters of each child were plotted on standard growth curves. The
      prevalence of obesity (body mass index at or above the 95th percentile), absolute
      weight at or above the 95th and 50th percentiles, underweight status, tall and
      short stature, macrocephaly and microcephaly were calculated. The prevalence of
      atypical findings was compared with the expected prevalence of typical growth
      parameters in the general population. Risk factors for atypical growth parameters
      were recorded. An association between weight and specific medication use was
      explored. RESULTS: It was found that 11.8% of the children were obese. It was
      also found that 23.5% of the children had weight at or above the 95th percentile,
      79.3% had weight at or above the 50th percentile, 14.7% had macrocephaly and
      79.4% had a head circumference above the 50th percentile; these results were
      statistically significant. The mean number of psychotropic medications prescribed
      was 6.4, although there was no significant association between higher weight and
      current medication type. CONCLUSIONS: Children receiving inpatient psychiatric
      treatment were more likely to have higher weight than typical children.
      Monitoring growth parameters is an important component of the paediatric care of
      children with psychiatric diagnoses. Guidelines are required for obesity
      prevention and intervention in the context of the risk factors experienced by
      this high risk population.

PMID- 20046277
TI  - Compliance with recommendations for routine HIV screening during pregnancy in
      Halifax.
AB  - BACKGROUND: The routine offering of testing for HIV during each pregnancy is
      recommended by various advisory bodies, including the Canadian Paediatric
      Society. OBJECTIVES: To determine the proportion of women in Nova Scotia who were
      counselled about HIV and HIV testing during their pregnancies and to determine
      the proportion of those who underwent the blood test after counselling. METHODS:
      A Self-administered survey at the IWK Health Centre, Halifax, Nova Scotia was
      performed. Questionnaires were distributed to 800 new mothers who delivered a
      child between March 10 and May 10, 2000. The questionnaire asked women for their
      ages, levels of education, history of previous deliveries, whether they had
      received counselling about HIV during their pregnancy, whether they were offered
      an HIV blood test and whether they underwent an HIV blood test. RESULTS: A total
      of 155 questionnaires were returned (response rate of 19.4%). The proportion of
      women who were counselled about HIV during their pregnancy was 65 of 155 (41.9%)
      (95% CI 34.1 to 49.7) and the proportion of those who were counselled who
      underwent the test was 47 of 65 (72.3%) (95% CI 65.3 to 79.3). There was a
      significant difference between the proportion counselled and history of previous
      deliveries (P=0.050), the proportion offered a test and their ages (P=0.028), and
      the proportion who had a test done and their ages (P=0.017). CONCLUSIONS: There
      is inadequate compliance with the recommendation that all women be offered HIV
      testing during each pregnancy at the IWK Health Centre. Health care professionals
      involved in obstetrics need to be reminded of the importance of HIV counselling
      and testing during pregnancy. Further evaluation throughout Canada of the effect
      of HIV screening recommendations during pregnancy is advisable.

PMID- 20046280
TI  - Announcing the new user-friendly CPSP Web site - a public health service
      resource.

PMID- 20046278
TI  - Chiropractic care for children: Controversies and issues.

PMID- 20046279
TI  - About inhalants.

PMID- 20046281
TI  - Clinician's Corner.

PMID- 20046282
TI  - Clinician's Corner.

PMID- 20046283
TI  - The fetus and alcohol - A preventable tragedy.

PMID- 20046285
TI  - Necrotizing fasciitis - A possible fatal varicella complication.

PMID- 20046284
TI  - Fetal alcohol spectrum disorder - New diagnostic initiatives.

PMID- 20046286
TI  - Paediatric health care - It's time to move forward.

PMID- 20046287
TI  - Telemedicine diagnosis for fetal alcohol syndrome - The Manitoba experience.
AB  - The diagnosis of fetal alcohol syndrome has been possible, with increasing
      precision, since the original descriptions in the 1970s. Multidisciplinary
      diagnostic approaches have been recognized as most appropriate, although they are
      often not available. Telemedicine has been used in Canada over the same time
      period for a variety of diagnositc applications.Since 1999, funding by the
      Manitoba government has allowed the consolidation of services for children with
      prenatal alcohol exposure in Manitoba, and has allowed the development of a
      format for diagnosis using telemedicine.This paper describes the authors'
      experience with the above and offers observations that may be helpful to other
      programs that are focused on developing this format for the diagnosis of fetal
      alcohol syndrome.

PMID- 20046288
TI  - Forensic issues in the assessment of sexually assaulted adolescents.
AB  - This article provides a general overview of the principles of conducting a
      forensic evaluation of adolescents who have been exposed to sexual abuse. This
      problem is common and is associated with a large burden of suffering. There is a
      strong likelihood that most paediatricians will be called on to perform such
      evaluations at some point in time. This overview includes a description of the
      forensic examination, focuses on such issues as consent and contact with child
      protection services, and provides specific guidelines about interviewing the
      adolescent. Familiarity with how to conduct a forensic evaluation will hopefully
      improve the availability of this service for adolescents. Contact with the legal
      profession can be stressful. At the same time, paediatricians are in a unique
      position to advocate on behalf of their adolescent patients.

PMID- 20046289
TI  - Fetal alcohol syndrome.
AB  - Alcohol is a physical and behavioural teratogen. Fetal alcohol syndrome (FAS) is
      a common yet under-recognized condition resulting from maternal consumption of
      alcohol during pregnancy. While preventable, FAS is also disabling.Although FAS
      is found in all socioeconomic groups in Canada, it has been observed at high
      prevalence in select First Nations and Inuit communities in Canada.This statement
      addresses FAS prevention, diagnosis, early identification and management for
      health care professionals.Prevention of FAS must occur at two levels. Primary
      prevention involves eliminating FAS through classroom or community education, and
      encouraging women to avoid consuming alcohol before conception and throughout
      pregnancy. Secondary prevention involves identifying women who are drinking while
      pregnant and reducing their consumption. This statement describes a variety of
      screening strategies including Tolerance-Annoyance, Cut Down, Eye Opener (T-ACE).
      Medical practitioners should recommend abstinence starting with the first
      prenatal visit. Prompt referral for alcohol treatment is recommended for pregnant
      individuals who are unable to stop drinking alcohol.This statement describes the
      diagnosis of FAS, partial or atypical FAS, alcohol-related birth defects and
      alcohol-related neurodevelopmental disorder. With a history of in-utero alcohol
      exposure, a diagnosis of FAS should be considered with current or previous growth
      deficiency, select facial abnormalities involving the upper lip and eyes, and
      neurodevelopmental abnormalities. These features are best quantified with the use
      of a four-digit diagnostic method.Strategies for early identification of possible
      alcohol-related abnormalities are outlined.Intervention focuses on optimizing
      development, managing behavioural difficulties and providing appropriate school
      programming. Of prime importance is earliest possible childhood intervention to
      prevent secondary disabilities that may result from delay while awaiting a
      definitive diagnosis of FAS.

PMID- 20046290
TI  - Fetal alcohol syndrome: What you should know about drinking during pregnancy.

PMID- 20046291
TI  - The gap between assessment and transfer.

PMID- 20046292
TI  - Diphtheria.

PMID- 20046293
TI  - The community paediatrician - A vanishing breed?

PMID- 20046294
TI  - Championing health care for children and youth: Ensuring Canada's future.

PMID- 20046295
TI  - Allergy to antibiotics in children: Perception versus reality.

PMID- 20046296
TI  - Demonstrating the clinical impact of your CPSP monthly feedback.

PMID- 20046297
TI  - Advances in paediatric migraine.
AB  - Headache is one of the most common complaints of children who present to primary
      care providers. Although parents are often concerned about sinister pathology,
      the majority of children with headaches have primary headache syndromes,
      including migraine and tension-type headaches. Diagnostic criteria for children
      are currently evolving to better reflect the unique challenges of this group of
      patients. Advances in migraine pharmacotherapy have been achieved through the
      understanding of serotonin and its role in migraine pathophysiology. Serotonin
      agonists, commonly known as 'triptans', are the current standard of care in the
      management of acute migraine in adults. Recent evidence has confirmed that the
      efficacy of triptans also occurs in children. The present article focuses on
      recent advances in the areas of epidemiology, diagnostic criteria and
      pathophysiology of paediatric migraine. In addition, the present article reviews
      the evidence of management issues, including neuroimaging and the use of triptans
      in children.

PMID- 20046298
TI  - The diagnosis and treatment of von Willebrand disease in children.
AB  - von Willebrand disease is the most common bleeding disorder seen in children and
      it affects approximately 1% of the population. Because the bleeding symptoms in
      von Willebrand disease are generally mild, the diagnosis is often delayed. Prompt
      diagnosis and management can help to avoid potentially life-threatening bleeding
      events and unnecessary exposure to blood products. In this review, the various
      types of von Willebrand disease are outlined, the difficulties in diagnosis are
      discussed and the therapeutic approach to this common disorder is described.

PMID- 20046299
TI  - A pacemaker for asystole in breath-holding spells.
AB  - Two cases of young children with frequent severe breath-holding spells
      complicated by prolonged asystole and seizures are reported. A ventricular
      pacemaker was implanted in each child, and both have subsequently remained free
      of syncope, although they continue to exhibit breath-holding behaviour.

PMID- 20046301
TI  - Playground safety.

PMID- 20046300
TI  - Preventing playground injuries.

PMID- 20046303
TI  - Ear infections (otitis media).

PMID- 20046302
TI  - Ankyloglossia and breastfeeding.

PMID- 20046304
TI  - Exercise therapy and the paediatrician: A compelling case.

PMID- 20046305
TI  - Injury prevention tips for healthy active living at home, school and in the
      community.

PMID- 20046306
TI  - The changing face of academic paediatrics in Canada.

PMID- 20046307
TI  - Psychosocial aspects of physical activity.

PMID- 20046308
TI  - Eating disorders and the practising physician.

PMID- 20046309
TI  - Healthy bones - Activity and nutrition.

PMID- 20046310
TI  - Evidence-based perinatal and paediatric health care: The contribution of the
      Cochrane Collaboration and the Canadian Cochrane Network and Centre.

PMID- 20046311
TI  - Surviving a hemolytic uremic syndrome.

PMID- 20046312
TI  - Evidence for clinical decisions.

PMID- 20046313
TI  - Obesity: A crisis of growing proportions.
AB  - Childhood obesity is a condition characterized by an imbalance between energy
      consumed and energy expended. A variety of factors that are unique to our modern
      day western society lead to the increasing prevalence of childhood obesity. The
      ease and volume of food supply, high calorie density, convenience foods,
      convenience transportation, sedentary lifestyle, school system issues, and
      perceptions of unsafe neighbourhoods all contribute to this increase in obesity.
      Consequences of childhood obesity are now known to carry health risks for
      childhood, as well as greater health risks in adulthood. A societal approach to
      solving this problem is necessary. The paediatrician's role as an advocate in
      society is vital. On an individual basis, paediatricians can help to identify
      these patterns early and prevent them by providing basic nutritional advice to
      the child and parents at an early stage.

PMID- 20046314
TI  - Type 2 diabetes, polycystic ovary syndrome and the insulin resistance syndrome in
      adolescents: Are they one big iceberg?
AB  - Obesity in children may cause overt clinical disease in childhood. The complex
      endocrine and metabolic changes of obesity and insulin resistance in adolescents
      result in hyperinsulinemia, dyslipidemia, hypertension, steatohepatitis, glucose
      intolerance, type 2 diabetes, acanthosis nigricans and ovarian hyperandrogenemia,
      commonly known as polycystic ovarian syndrome (PCOS). Type 2 diabetes and PCOS in
      adolescents are new endocrine diseases in this age group that require unique
      approaches to diagnosis and treatment. The direct correlation between duration of
      disease and control of the disease, and subsequent long term complications of
      these two diseases, predict serious morbidity in young adult life for the
      affected adolescents. Pediatricians have an important role in the prevention,
      diagnosis and treatment of obesity, insulin resistance syndrome, type 2 diabetes
      and PCOS.

PMID- 20046315
TI  - Healthy active living for children and youth.
AB  - Poor lifestyle habits, such as unhealthy eating and physical inactivity, are
      major contributors to increased adult morbidity and mortality from chronic
      diseases. Over the past decade there has been an increase in sedentary lifestyle
      and obesity in children and adolescents, both in North America and worldwide.
      Physicians need to be aware of the scope of this problem, provide anticipatory
      guidance to families and promote healthy active living in their practices.

PMID- 20046316
TI  - Healthy active living for children and youth.

PMID- 20046317
TI  - Unravelling an acute flaccid paralysis event.

PMID- 20046318
TI  - The fall and rise of rickets.

PMID- 20046319
TI  - Office-based research: A new era and new opportunities.

PMID- 20046320
TI  - Management of bacterial meningitis in children: Controversies in the management
      of bacterial meningitis.

PMID- 20046321
TI  - Controversies in the management of bacterial meningitis.
AB  - Bacterial meningitis is an important infection of childhood with significant
      morbidity and mortality, and clinicians are faced with controversies over steroid
      use and fluid restriction in its initial management because the standard of
      practice is not clear. A 1999 survey of paediatric infectious diseases
      specialists demonstrated that only 56% of respondents recommended dexamethasone
      for Haemophilus influenzae type b meningitis and only 34% recommended
      dexamethasone for Streptococcus pneumoniae meningitis, despite recommendations
      for dexamethasone in the 1997 Red Book. The present article illustrates a typical
      case presentation of bacterial meningitis, and discusses dexamethasone use and
      fluid restriction. The use of intravenous fluid therapy is also reviewed, based
      on results from the single prospective randomized clinical trial in this area.

PMID- 20046322
TI  - Congenital rickets caused by maternal vitamin D deficiency.
AB  - The cases of four newborn infants with congenital rickets are reported. All
      infants were native Canadian: three were Cree and one was Inuit. One had a narrow
      chest and pulmonary hypoplasia, two had clinical and radiological signs of
      rickets with craniotabes, thickened wrists, and prominent costochondral
      junctions, and one had perinatal asphyxia and hydrops. All had hypocalcemia,
      hypophosphatemia and secondary hyperparathyroidism. Serum 25-hydroxyvitamin D
      levels were low in three of the infants. The four mothers had evidence of vitamin
      D deficiency. All infants recovered following treatment with 5000 IU oral vitamin
      D daily.

PMID- 20046324
TI  - Vitamin d.

PMID- 20046323
TI  - Vitamin D supplementation in northern Native communities.

PMID- 20046326
TI  - Illiteracy - fighting the hidden epidemic.

PMID- 20046327
TI  - A library in my practice, why not?

PMID- 20046325
TI  - Recommendations for the prevention of neonatal ophthalmia.
AB  - Despite the decreasing prevalence of Neisseria gonorrhoeae in Canada, the
      Canadian Paediatric Society recommends that, as soon as possible after birth, all
      infants receive prophylaxis with silver nitrate, tetracycline or erythromycin, to
      reduce the risk of neonatal ophthalmia due to this organism. The use of these
      agents may also provide some benefit in the prevention of ophthalmia due to other
      organisms. As well, the Canadian Paediatric Society supports routine pre-natal
      screening for N gonorrhoeae and Chlamydia trachomatis, and the treatment of
      identified infections during pregnancy.

PMID- 20046328
TI  - Preventing group B streptococcal infections: New recommendations.

PMID- 20046329
TI  - Acute immune thrombocytopenic purpura: What do we do when things go well?

PMID- 20046330
TI  - Hospitalization of children with acute immune thrombocytopenic purpura - is it
      necessary?
AB  - OBJECTIVE: To identify a target group of children with acute immune
      thrombocytopenic purpura (ITP) that may not require hospitalization for
      management. METHODS: A retrospective chart review was conducted of all children
      admitted over a two-year period to a tertiary care paediatric hospital with the
      diagnosis of acute ITP. Patients were classified according to typical and
      atypical presentations. Typical patients were defined as those aged between one
      and 10 years, with no hepatomegaly or significant splenomegaly and who had
      typical laboratory features for ITP. Patients who did not meet these criteria
      were categorized as atypical. Outcome measures included length of stay (LOS) in
      hospital; frequency of bone marrow aspiration (BMA); type of treatment; incidence
      of intracranial hemorrhage (ICH) or severe bleeding; and admission and discharge
      platelet counts. RESULTS: There were 74 patients hospitalized for a mean of 3.6
      days. No patients suffered an ICH or bleeding requiring transfusion. Patients
      with typical presentations (42) were compared with patients with atypical
      presentations (32) and were not significantly different for clinically important
      outcomes such as admission and discharge platelet counts, serious complications
      or type of therapy. Typical patients had significantly fewer BMAs than did
      atypical patients - 22 of 42 (52%) versus 25 of 32 (78%) (P=0.02), and a shorter
      LOS - 3.1 (+/-0.9) days versus 4.2 (+/-1.8) days (P=0.01). CONCLUSIONS: Children
      presenting with ITP have a low incidence of bleeding complications and many of
      these patients can be managed as outpatients. A multicentre study is needed to
      properly delineate a low risk group suited for outpatient medical management.

PMID- 20046331
TI  - Dexamethasone and antibiotics for the empirical treatment of bacterial meningitis
      in Canadian children: A survey of paediatric infectious diseases specialists.
AB  - PURPOSE: With the changing epidemiology of the etiological agents causing
      bacterial meningitis in Canada, the purposes of this study were to determine what
      empirical antibiotic(s) is/are advocated, and whether dexamethasone is
      recommended as adjunctive therapy by paediatric infectious diseases specialists
      for suspected meningitis caused by Streptococcus pneumoniae, Neisseria
      meningitides, Haemophilus influenzae type b, and partially treated (PT) bacterial
      meningitis. METHODS: A questionnaire invoking the specialists' preferred choices
      in treating bacterial meningitis was circulated by e-mail in March 1999 to 41
      paediatric infectious diseases specialists or microbiologists (Paediatric
      Investigators Collaborative Network on Infections in Canada [PICNIC] members) who
      practised in 13 paediatric centres located in eight provinces. RESULTS: Thirty
      two (78% response rate) replies were received by July 1999 from 11 paediatric
      centres in seven provinces. Dexamethasone was recommended by 11 of 32 (34%)
      respondents for suspected S pneumoniae, four of 32 (12%) for suspected N
      meningitides, 18 of 32 (56%) for suspected H influenzae type b and five of 32
      (16%) for suspected PT meningitis. A trend for more frequent recommended use of
      dexamethasone for S pneumoniae, H influenzae type b and N meningitides meningitis
      was found in eastern provinces (Ontario, Quebec and Nova Scotia), as opposed to
      the western provinces (Manitoba, Saskatchewan, Alberta and British Columbia). The
      most commonly recommended first line empirical antibiotic therapy was vancomycin
      plus 3rd-generation cephalosporin (V+3C). This was recommended by 27 of 32 (84%)
      respondents for suspected S pneumoniae, seven of 32 (22%) for suspected N
      meningitides, six of 32 (19%) for suspected H influenzae type b and 24 of 32
      (75%) for PT meningitis; the remainder recommended using a 3C empirically for
      each type of meningitis. The major reason cited by respondents for using V+3C for
      suspected S pneumoniae was the presence of high-and intermediate-level penicillin
      resistant S pneumoniae in their centres. No differences were found in the choice
      of antibiotic(s) between practitioners in the eastern and western provinces.
      CONCLUSIONS: Although regional differences exist, the majority of paediatric
      infectious diseases experts no longer favour the use of dexamethasone for
      empirical therapy in most cases of bacterial meningitis. V+3C has become the
      regimen of choice in Canada for most cases of suspected bacterial meningitis.

PMID- 20046332
TI  - Promoting literacy in the physician's office.

PMID- 20046333
TI  - A parent's guide to promoting reading in children.

PMID- 20046334
TI  - Pneumococcal vaccine for children.

PMID- 20046335
TI  - Baby walker survey: Results and next steps.

PMID- 20046336
TI  - Meningococcal vaccine for children.

PMID- 20046337
TI  - Neurophyisological and neurocognitive endophenotypes for schizophrenia genetics
      research.
AB  - There is growing interest in the genetic analysis of schizophrenia using
      endophenotypes rather than clinical diagnosis or symptom dimensions.
      Endophenotypes could be alternative phenotypes for the clinical phenotypes. With
      their intermedicate and quantitative characteristics, endophenotypes could be
      functionally important links in the pathways between the genetic variation and
      clinical expression of the disorder. In this regard, the neurophysiological and
      neurocognitive endophenotypes used in the genetic analysis of schizophrenia have
      been reviewed.

PMID- 20046338
TI  - Peripheral amino Acid levels in schizophrenia and antipsychotic treatment.
AB  - Abnormal levels of amino acids have been reported in patients with schizophrenia
      and have also been investigated as a biomarker to monitor antipsychotic
      treatment, however results have been inconsistent. The purpose of the present
      review is to summarize the evidence in the literature of whether amino acid
      levels can be a biomarker and predict the treatment outcome in schizophrenia. The
      current review does not support amino acid concentration as a useful biomarker
      for monitoring antipsychotic response in patients with schizophrenia, although
      there is evidence that high levels of serum homocysteine and glutamate might be
      considered as a trait marker for schizophrenia. This review has also highlighted
      a considerable dearth of studies, specifically of studies evaluating
      antipsychotic side-effects.

PMID- 20046339
TI  - Treatment of chronic fatigue syndrome: findings, principles and strategies.
AB  - Chronic fatigue syndrome (CFS) is a debilitating condition characterized by
      serious medically unexplained mental and physical fatigue. The high prevalence
      and both direct and indirect health costs of CFS patients represent a huge
      problem for contemporary health care. Moreover, the prognosis of CFS, even when
      treated, is often poor. In this paper, we first critically review current
      evidence based treatments of CFS. Second, we discuss the growing insights into
      the etiopathogenesis of CFS, and the need to translate and integrate these
      insights into future treatments. In particular, we formulate a pragmatic and
      empirically testable treatment approach, tailored to the individual needs of
      patients, which aims at restoring the mental and physical equilibrium of CFS
      patients by trying to bring about sustained life style changes.

PMID- 20046340
TI  - Traumatic experiences and mental health of north korean refugees in South Korea.
AB  - OBJECTIVE: This study was conducted at Hanawon-a government sponsored educational
      facility for the settlement of North Korean refugees during their initial phase
      in South Korea-in 2004 to explore their mental health status and traumatic
      experiences in North Korea and during their escape period. METHODS: A survey was
      conducted in November 2004 with 62 North Korean refugees at Hanawon, and the
      Trauma Checklist was used to measure their traumatic experiences. To measure
      their psychological-mental health status, the Personality Assessment Inventory
      was administered. RESULTS: In comparison with the traumatic experiences of the
      North Korean refugees found in the study conducted in 2001 at Hanawon using the
      same methods, the current study showed a relatively lower frequency of traumatic
      experiences among the participants. The Personality Assessment Inventory results
      revealed that the study participants scored higher than average South Koreans in
      all clinical scales. Particularly, their mania (62.51) and schizophrenia (61.75)
      scores were above 60, a clinically meaningful score. In the gender comparison,
      the males exhibited meaningfully higher levels of alcohol problem, non-support,
      and warmth scale scores. CONCLUSION: Compared to the 2001 study, the overall
      traumatic experiences among North Korean refugees participated in this study. But
      continous support is necessary for their successful adaptation to South Korean
      Society have declined. The North Korean refugees at Hanawon experienced
      difficulties maintaining their mental health and the men in particular requested
      more intensive care and support for this purpose.

PMID- 20046341
TI  - Intensive psychotherapy training in korean psychiatric residency programs.
AB  - OBJECTIVE: The authors investigated the current practice of intensive
      psychotherapy by residents in the department of psychiatry. METHODS: We mailed a
      questionnaire to 126 fourth-year psychiatry residents in order to obtain data on
      their clients' sociodemographic characteristics, the settings in which
      psychotherapy is being conducted, the effects of psychotherapy, the difficulties
      associated with psychotherapy, the state of supervision and the level of clients'
      satisfaction. RESULTS: Approximately 51.5% of the residents completed the
      questionnaires. The average number of clients was 4.9+/-3.8, the average number
      of psychotherapy sessions was 26.2+/-20.1, and 69.4% of the residents had
      performed insight-oriented psychotherapy. Approximately 69.8% of the fourth-year
      residents had received some form of supervision, and 58.7% agreed to increase the
      frequency of supervision. Approximately 74.2% of the cases were supervised. The
      average number of supervisions per case was 9.2+/-10.5. CONCLUSION: The setting
      in which psychotherapy is conducted, number of clients, and type of supervision
      varied greatly among the training institutes surveyed. Based on these findings,
      we expect to create better psychotherapy training programs for psychiatric
      residents.

PMID- 20046342
TI  - Personality characteristics of mothers of children with attention deficit
      hyperactivity disorder as assessed by the Minnesota multiphasic personality
      inventory.
AB  - OBJECTIVE: The current study investigated the personality characteristics of
      mothers of children with attention deficit hyperactivity disorder (ADHD) using
      the Minnesota Multiphasic Personality Inventory (MMPI). METHODS: Fifty mothers
      (average age of 38.1+/-4.2 years) of children with ADHD not having comorbidity
      (37 boys, 13 girls; average age of 8.5+/-1.9 years) and 59 mothers (average age
      of 38.1+/-2.7 years) of comparison children (37 boys, 13 girls; average age of
      8.1+/-1.5 years) completed the Korean version of the MMPI. Only mothers whose
      psychiatric health was verified by the Structured Clinical Interview for axis-I
      DSM-IV disorders (SCID-IV) were included in current study. RESULTS: After
      controlling for maternal age, maternal education level, children's gender, age,
      and total and verbal intelligence quotient (IQ), the MMPI scores of the mothers
      of children with ADHD were significantly higher on the depression (D), hysteria
      (Hy) and psychasthenia (Pt) scales than those of the mothers of children in the
      comparison group. CONCLUSION: These results suggested that even psychologically
      healthy mothers of children with ADHD alone might be depressed, histrionic and
      anxious.

PMID- 20046343
TI  - Standardization of the korean version of the geriatric depression scale:
      reliability, validity, and factor structure.
AB  - OBJECTIVE: We developed a Revised Korean version of the Geriatric Depression
      Scale (GDS-KR) and examined its reliability, validity, and factor structures. We
      also estimated its optimal cutoff scores for major depressive disorder (MDD) and
      minor depressive disorder (MnDD) stratified by age and education. METHODS: The
      GDS-KR was administered to 888 subjects (61 MDD patients, 45 MnDD patients, and
      782 normal elders). Its internal consistency and test-retest reliability were
      examined. Its concurrent validity was evaluated using Pearson correlation
      coefficients with the Korean version of the Center for Epidemiologic Studies
      Depression Scale (CES-D-K) and Hamilton Depression Rating Scale (HAM-D). The mean
      GDS-KR scores of the MDD patients, MnDD patients and normal elders were compared
      to evaluate its discriminant validity. To evaluate its construct validity, a
      principal component analysis with varimax rotation was performed. Receiver
      operator characteristic (ROC) curve analyses were performed to evaluate its
      diagnostic ability. RESULTS: Chronbach's coefficient alpha for the GDS-KR was
      0.90 and the test-retest reliability was 0.91 (p<0.01). The Pearson correlation
      coefficients of the GDS-KR scores with the CES-D-K and HAM-D scores were 0.63
      (p<0.01) and 0.56 (p<0.01), respectively. The GDS-KR consisted of 5 factors. The
      optimal cut-off scores of the GDS-KR were 16/17 for MDD only and 15/16 for both
      MDD and MnDD. The optimal cutoff scores of the GDS-KR were higher in the less
      educated and younger subjects. The diagnostic accuracy for MDD of the GDS-KR was
      higher than that of the CES-D. CONCLUSION: The GDS-KR was found to be a reliable
      and valid questionnaire for screening MDD and MnDD in late life.

PMID- 20046344
TI  - Social pressure-induced craving in patients with alcohol dependence: application
      of virtual reality to coping skill training.
AB  - OBJECTIVE: This study was conducted to assess the interaction between alcohol
      cues and social pressure in the induction of alcohol craving. METHODS: Fourteen
      male patients with alcohol dependence and 14 age-matched social drinkers
      completed a virtual reality coping skill training program composed of four blocks
      according to the presence of alcohol cues (x2) and social pressure (x2). Before
      and after each block, the craving levels were measured using a visual analogue
      scale. RESULTS: Patients with alcohol dependence reported extremely high levels
      of craving immediately upon exposure to a virtual environment with alcohol cues,
      regardless of social pressure. In contrast, the craving levels of social drinkers
      were influenced by social pressure from virtual avatars. CONCLUSION: Our findings
      imply that an alcohol cue-laden environment should interfere with the ability to
      use coping skills against social pressure in real-life situations.

PMID- 20046345
TI  - Association Study of a Serotonin Receptor 2A Gene -1438A/G Polymorphism and
      Anxiety-Related Traits.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between the 
      1438A/G polymorphism of serotonin receptor 2A (5HTR2A) and anxiety-related traits
      in Korean adolescent females. METHODS: A total of 174 Korean adolescent females
      were tested for the -1438A/G polymorphism of 5HTR2A using polymerase chain
      reaction (PCR)-based methods. Anxiety-related traits were evaluated using the
      Anxiety Sensitivity Index (ASI) and the trait form of the Spielberg State-Trait
      Anxiety Inventory (T-STAI). RESULTS: There was no difference between the
      genotypes with respect to scores pertaining to anxiety-related traits. Although
      the G allele carriers (GG or AG genotype) scored lower on the psychological
      subscale of the ASI (4.76+/-3.00 vs 5.98+/-4.00, p=0.038), this difference was
      not significant after Bonferroni correction. CONCLUSION: These findings suggest
      that the -1438A/G polymorphism of 5HTR2A might not be associated with anxiety
      sensitivity or trait anxiety.

PMID- 20046346
TI  - Serial Monitoring of Lead aVR in Patients with Prolonged Unconsciousness
      Following Tricyclic Antidepressant Overdose.
AB  - Severe cardiac and neurologic toxicities of tricyclic antidepressant (TCA)
      overdose have been reported since the introduction of TCAs in 1950s. Despite the
      decreased numbers of TCA overdoses, the mortality and morbidity rates of TCA
      overdose have remained constantly high. Clinical manifestations of TCA overdose
      are characterized by unconsciousness and specific electrocardiography (ECG)
      abnormalities such as prolongation of the PR and QTc intervals, widening of the
      QRS duration, and an increased R wave and R/S ratio in lead aVR. We report a case
      with unusually prolonged unconsciousness without initial stem reflexes for 7 days
      and multiple ECG abnormalities following TCA overdose. It is suggested that the
      serial monitoring of R wave and R/S ratio in lead aVR might be informative in
      predicting recovery from toxicity following TCA overdose.

PMID- 20046347
TI  - The wind of change in psychiatric publications.
AB  - It is getting more difficult to get papers published that it used to be, even
      though many more journals are available. This article is written mainly for young
      researchers who are ambitious to get their research published in the best
      possible journals. A systematic strategic policy is suggested that does not
      necessarily contradict the aims of achieving the best possible science.

PMID- 20046348
TI  - Mental health of north korean refugees in protective facilities in china.
AB  - OBJECTIVE: This study aims to provide alternative care plans for mental health of
      North Korean refugees who are in protective facilities in China. METHODS:
      Personality Assessment Inventory (PAI) was utilized to measure the
      presence/absence of post traumatic stress disorder (PTSD) among 65 North Korean
      refugees. RESULTS: The gender differences in PAI t-scores showed that women
      exhibited meaningfully higher scores largely in anxiety (m=61.85), depression
      (m=65.23), and schizophrenia (m=60.98). In different age groups, schizophrenia in
      the 30 age bracket (m=65.23) was meaningfully higher than the teens (m=48.11).
      Aggression among the treatment features was the highest in the 20 age group
      (m=59.19) showing higher t-scores than the teens (m=39.67). Duration in the
      facility affected mental health in that the 3-5 years group (m=63.91) reported
      the highest in paranoia. Groups of under 1 year and less than 1-3 years showed
      meaningfully higher scores in nonsupport. The PTSD (including partial PTSD) rate
      of the group recorded 9.2%. Correlation between the PTSD and PAI scores showed
      that the full-PTSD group demonstrated higher average scores in negative
      impression, somatic complaints, anxiety, anxiety-related disorder, depression,
      paranoia, schizophrenia, antisocial features, suicide ideation, and treatment
      rejection than the non-PTSD group. CONCLUSION: Mental health of North Korean
      refugees in China was worse in women, the thirties, and less than 3-5 years in
      the facility, and it deteriorated as the duration prolonged. To promote better
      psychological health of North Korean refugees in China, the attention and aid
      from the protection facilities and domestic and international interests are
      required.

PMID- 20046349
TI  - Prevalence of Alzheimer's dementia and its risk factors in community-dwelling
      elderly koreans.
AB  - OBJECTIVE: We estimated the prevalence of Alzheimer's dementia (AD) and mild
      cognitive impairment (MCI) and their risk factors in an urban community setting,
      focusing especially on metabolic syndrome. METHODS: A two-phase investigation
      based on a door-to-door survey was performed. In Phase I, we administered the
      Korean version of the Mini-Mental State Examination (MMSE-KC) of the Consortium
      to Establish a Registry for Alzheimer's disease (CERAD-K). Assessment Packet and
      the Korean version of the Geriatric Depression Scales (GDS-K) to all 706
      participants aged 65 years or older. In Phase II of the study, 175 persons
      underwent physical and neurological examinations according to the protocol of the
      CERAD-K clinical assessment battery [CERAD-K (C)] and the neuropsychological
      assessment battery [CERAD-K (N)]. We also examined the association between
      cognitive decline and metabolic syndrome. AD and MCI were defined using the DSM
      IV-TR criteria and the Clinical Dementia Rating (CDR) scales. RESULTS: The mean
      age (+/-SD) of the subjects was 74.3+/-16.7 years and the ratio of males to
      females was 53.2 to 46.8. The prevalence of Alzheimer's dementia was 9.0%, while
      that of MCI was 32.9%. Old age and lower educational level had significant
      associations with cognitive decline in the elderly, but gender, years of alcohol
      intake or smoking, and metabolic syndrome were not associated with AD or MCI.
      CONCLUSION: In this study, metabolic syndrome was not associated with Alzheimer's
      AD or MCI. Information regarding an association between Alzheimer's dementia and
      metabolic syndrome in this study will be helpful in formulating future public
      health policy and prevention strategies in Korea.

PMID- 20046350
TI  - Prevalence and risk factors associated with suicide ideation and attempts in
      korean college students.
AB  - OBJECTIVE: Suicide is a leading cause of death in college age students.
      Identification of the associated risk factors has important implications for how
      to prevent and respond to this population; however, few studies have been
      performed on this topic in this age group. The purpose of this study was to
      evaluate the prevalence and risk factors associated with suicide ideation and
      attempts in college students. METHODS: Three hundred sixty-eight college students
      participated in this cross-sectional observational study. The recent (over two
      weeks) suicide ideation and lifetime suicide attempts were defined according to
      Moscicki's suicide behavior index. Sociodemographic variables were assessed and
      psychopathology measured using the Beck Depression Inventory, the Bipolar
      Spectrum Diagnostic Scale and the Alcohol Use Disorders Identification Test. A
      hierarchical multiple logistic regression analysis was used to identify the
      significant risk factors related to suicide ideation and attempts. RESULTS: The
      two-week prevalence of suicidal ideation was 9.8%, and the lifetime prevalence of
      suicide attempts was 3.3%. The univariate analysis showed that students who had
      more severe depression (p<0.001), a higher probability for bipolar disorder
      (p<0.001) and decrement of academic achievement (p<0.005) were more likely to
      have suicide ideation. Those with factors such as severe depression (p<0.05), a
      higher probability of bipolar disorder (p<0.001), a low socioeconomic status
      (p<0.001), who lived alone (p<0.01), and were female (p<0.05) had a higher risk
      for suicide attempts. The most important predictors of suicide ideation, by the
      logistic regression analysis, were depression, probability for bipolar disorder
      and academic achievement, and the risks identified for suicide attempts were
      socioeconomic status and probability of bipolar disorder. CONCLUSION: Suicide
      ideation and attempts were common in college students. The results of this study
      suggest that early identification and management of mood disorders and other
      sociodemographic risk factors may have implications for intervention and
      prevention.

PMID- 20046351
TI  - Interaction between Neuronal Depolarization and MK-801 in SH-SY5Y Cells and the
      Rat Cortex.
AB  - OBJECTIVE: The interaction between MK-801, a model of psychosis and KCl-induced
      depolarization or electroconvulsive shock (ECS), a therapeutic model of
      electroconvulsive therapy (ECT), was investigated in SH-SY5Y cells and the rat
      frontal cortex. METHODS: SH-SY5Y cells were pretreated with 1 microM MK-801 for
      15 min, followed by cotreatment with 100 mM KCl for 5 min. MK-801 was
      reintroduced after the KCl was washed out, and the samples were incubated before
      harvesting. For the experiments in rats, male Sprague-Dawley rats were treated
      with MK-801 followed by ECS. Immunoblot analyses of glycogen synthase kinase
      3beta (GSK3beta) (Ser9), AKT (Ser473) and extracellular legulated kinase (ERK)1/2
      in SH-SY5Y cells and the rat frontal cortex were performed. RESULTS: KCl-induced
      neuronal depolarization resulted in the transient dephosphorylation of AKT
      (Ser473) and GSK3beta (Ser9), followed by increased phosphorylation of the
      enzymes in SH-SY5Y cells. Cotreatment with MK-801 and KCl inhibited the initial
      dephosphorylation of AKT and GSK3beta produced by KCl-induced neuronal
      depolarization. Similarly, ECS resulted in the transient dephosphorylation of AKT
      (Ser473) and GSK3beta (Ser9), whereas cotreatment with MK-801 inhibited the
      initial dephosphorylation of AKT (Ser473) and GSK3beta (Ser9) produced by ECS in
      the rat frontal cortex. No significant interaction was observed between MK-801
      and KCl in the dephosphorylation of ERK1/2. CONCLUSION: These results suggest
      that an antagonistic interplay between MK-801 and neuronal depolarization by KCl
      or ECS is involved the regulation of AKT (Ser473) and GSK3beta (Ser9)
      phosphorylation.

PMID- 20046352
TI  - Effect of the dysbindin gene on antimanic agents in patients with bipolar I
      disorder.
AB  - OBJECTIVE: We previously reported an association between dysbindin gene (DTNBP1)
      variants and bipolar I disorder (BID). This paper expands upon previous findings
      suggesting that DTNBP1 variants may play a role in the response to acute mood
      stabilizer treatment. METHODS: A total of 45 BID patients were treated with
      antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52
      (+/-19.87) days. After treatment, the patients were evaluated using the Clinical
      Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and
      genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A,
      rs760761 C/T and rs2619522 A/C). RESULTS: There was no association between the
      variants investigated and response to mood stabilizer treatment, even after
      considering possible stratification factors. CONCLUSION: Although the small
      number of subjects is an important limitation in our study, DTNBP1 does not seem
      to be involved in acute antimanic efficacy.

PMID- 20046353
TI  - Cognitive factors for predicting treatment response in schizophrenic patients:
      one-year follow-up study.
AB  - OBJECTIVE: This study was conducted to investigate the cognitive factors that can
      longitudinally predict the response to treatment in patients with schizophrenia.
      METHODS: The subjects were 49 patients with schizophrenia who were newly
      hospitalized in an acute psychiatry ward and had not been treated with medication
      for at least 8 weeks prior to the study. The symptoms and cognitive functions of
      the patients were evaluated at baseline before treatment (T0), at eight weeks
      after treatment (T1), and one year after treatment (T2). Clinical symptoms were
      assessed using the PANSS, and cognitive functions were estimated using the
      Vigilance Test, Cognitrone Test, Wisconsin Card Sorting Test (WCST), and the
      Korean version of the Memory Assessment Scales (K-MAS). RESULTS: The patient
      group showed marked impairments in cognitive function when compared to the normal
      group, but the patients' clinical symptoms and cognitive functions improved after
      drug treatment. The patients also showed consistent improvement in verbal and
      nonverbal memory function as time progressed. Furthermore, there was a
      significant correlation between clinical symptoms and cognitive functions in the
      patient group. The cognitive variables that best predicted treatment response and
      prognosis were total errors on the WCST and immediate list recall component of
      the K-MAS. It was also shown that the number of total errors on the WCST was a
      better cognitive predictor than the number of errors in immediate recall.
      CONCLUSION: The results of the present study show that the neurocognitive
      functions of patients with schizophrenia can be stabilized with treatment
      intervention, that treatment response is related to improvement in cognitive
      function, and that cognitive domains, especially executive function, can predict
      treatment response and prognosis in patients with schizophrenia.

PMID- 20046354
TI  - Nonlinear analysis of electroencephalogram in schizophrenia patients with
      persistent auditory hallucination.
AB  - OBJECTIVE: The recent nonlinear analyses of electroencephalogram (EEG) data have
      shown that the correlation dimension (D2) reflects the degree of integration of
      information processing in the brain. There is now considerable evidence that
      auditory hallucination (AH) reflects dysfunctional gamma and beta frequency
      oscillations. Gamma oscillations are thought to reflect internally driven
      representations of objects, and the occurrence of subsequent beta oscillations
      can reflect the modification of the neuronal circuitry used to encode the sensory
      perception. The purpose of this study was to test whether AH in schizophrenia
      patients is reflected in abnormalities in D2 in their EEG, especially in the
      gamma and beta frequency bands. METHODS: Twenty-five schizophrenia patients with
      a history of treatment-refractory AH over at least the past 2 years, and 23
      schizophrenia patients with no AH (N-AH) within the past 2 years were recruited
      for the study. Artifact-free 30-s EEG epochs during rest were examined for D2.
      RESULTS: The AH patients showed significantly increased gamma frequency D2 in Fp2
      and decreased beta frequency D2 in the P3 region compared with the N-AH patients.
      These results imply that gamma frequency D2 in the right prefrontal cortex is
      more chaotic and that beta frequency D2 in the left parietal cortex is more
      coherent (less chaotic) in AH patients than in N-AH patients. CONCLUSION: Our
      study supports the previous evidence indicating that gamma and beta oscillations
      are pivotal to AH, and also shows the distinctive dimensional complexity between
      the right prefrontal and left parietal cortexes as the underlying biological
      correlates of AH in schizophrenia patients.

PMID- 20046355
TI  - Three cases of reversible agranulocytosis after treatment with lamotrigine.
AB  - Several psychotropic drugs, including clozapine, are known to cause
      agranulocytosis and this may lead to a fatal condition. Lamotrigine is an
      anticonvulsant that the Food and Drug Administration (FDA) has approved for the
      depression of bipolar disorder. A few cases of lamotrigine-induced
      agranulocytosis have been previously reported on, but the pathophysiology and
      clinical manifestations are not yet known. This case series reports on 3 patients
      with different medical conditions who experienced agranulocytosis during
      treatment with lamotrigine. In these cases, the agranulocytosis occurred a few
      weeks after initiation of lamotrigine and it rapidly disappeared after
      discontinuation. We also discuss several characteristics of lamotrigine-induced
      agranulocytosis.

PMID- 20046356
TI  - Clinical correlates of hwa-byung and a proposal for a new anger disorder.
AB  - This paper reviewed the studies on hwa-byung (HB), which literally means anger
      disorder and this is known as the culture-related chronic anger syndrome of
      Koreans. Based on these studies and a review of the literature on the anger
      syndromes of other cultures, I have proposed a new anger disorder. The rationale
      for this proposition is first that the clinical correlates of HB, including the
      epidemiological data, the etiological factors, the symptoms and the clinical
      course, are unique and different from those of the depressive disorders, which
      have been postulated to be similar to HB. Second, the symptoms of HB are
      characterized by pent-up anger and somatic and behavioral symptoms related to the
      release and suppression of anger. Third, a group of patients with only HB and who
      visit psychiatrists for treatment have been identified. Fourth, anger is thought
      to be the basic target of treatment for HB patients. Last, anger syndromes like
      HB have been identified, with various names, in other cultures. By reducing the
      cultural variation of HB and integrating the common clinical correlates of the
      syndromes related to anger, a new anger disorder for the mood of anger can be
      conceptualized, like that for other mood disorders for the corresponding
      pathological moods. The research diagnostic criteria for HB and the new anger
      disorder are also suggested. I propose that the new anger disorder to be included
      in the new international classification system as a member of the larger family
      of mood disorders. International collaborative studies are needed not only to
      identify such anger disorder in various cultures, but also to explore giving
      better treatment to these patients based on the bio-psycho-social model of anger
      disorder.

PMID- 20046357
TI  - Triple reuptake inhibitors: a premise and promise.
AB  - On the horizon there is a new class of psychoactive medications which work by
      inhibiting the neuronal reuptake of serotonin, norepinephrine, and dopamine.
      There are multiple potential indications for these drugs. Research suggests that
      they may have a role in treating depressive disorders, and it is plausible they
      may have potential efficacy in obesity, addiction, and pain syndromes. The
      current review describes some of the molecules in development presently and
      explores the research relevant to possible clinical uses for this class of
      medications.

PMID- 20046358
TI  - The emotional characteristics of schizotypy.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      emotional traits and schizotypal symptoms and to establish a hypothetical model
      for the causal relationship between them. METHODS: Schizotypal symptoms were
      assessed using the Schizotypal Personality Questionnaire (SPQ), and a total of
      seven emotional traits considered to be potential risk factors for schizotypy
      were categorized as emotional disturbances, emotional attenuators or emotional
      amplifiers. A total of 502 undergraduate students completed the SPQ and other
      scales. RESULTS: The result of the present study suggested that the high levels
      of emotional disturbance in individuals who are prone to schizotypy or psychosis
      are amplified by their intensity and fluctuation. However, if their emotion
      attenuating abilities function well, these disturbances can be controlled and the
      schizotypal symptoms and progression to psychosis can be contained. Discriminant
      analysis showed that 69.0% of the subjects with many schizotypal symptoms and
      80.7% of the subjects with few schizotypal symptoms were correctly classified.
      CONCLUSION: The present study suggests the possibility of using emotional traits
      to identify the risk factors for psychosis.

PMID- 20046359
TI  - Impacts of poor social support on general health status in community-dwelling
      korean elderly: the results from the korean longitudinal study on health and
      aging.
AB  - OBJECTIVE: We investigated the influence of social support on health, quality of
      life (QOL), and the risk of depression in elderly Korean people. METHODS: This
      study was conducted as a part of the Korean Longitudinal Study on Health and
      Aging (KLoSHA). A total of 787 nondemented community-dwelling elderly aged 65
      years or older were recruited and underwent clinical evaluations for dementia and
      psychiatric disorders conformed to Korean version of the Consortium to Establish
      a Registry for Alzheimer's Disease Clinical Assessment Battery (CERAD-K) and the
      Korean version of the Mini-International Neuropsychiatric Interview (MINI),
      respectively. Social support was assessed using the Medical Outcome Study Social
      Support Survey (MOS-SSS). Poor social support (PSS) was defined as having a MOS
      SSS score below the 25(th) percentile of the entire sample. General health status
      was comprehensively evaluated using the modified Cumulative Illness Rating Scale
      (CIRS), the Korean version of the Geriatric Depression Scale (GDS-K), Mini-Mental
      Status Examination (MMSE-KC), Korean Activities of Daily Living (KADL), and
      Korean Instrumental Activities of Daily Living (KIADL). Health-related QOL was
      evaluated using the Short Form 36 (SF-36). RESULTS: Low educational attainment
      and living alone were associated with PSS. Geriatric depression was more
      prevalent in the PSS group (OR=3.05, 95% CI=1.77-5.27) than in the normal social
      support (NSS) group. Among the various forms of social support, positive social
      interaction was significantly associated with risk of geriatric depression
      (OR=2.25, 95% CI=1.07-4.73). Although health-related QOL was lower in the PSS
      group than in the NSS group, the ADL and IADL scores of the subjects in the PSS
      group were better than those of the subjects in the NSS group. In the subjects
      with geriatric depression, PSS was associated with more severe depression, higher
      medical morbidity, and poor QOL. CONCLUSION: PSS had a negative influence on the
      general health status and QOL among community-dwelling elderly and was an
      independent risk factor of geriatric depression.

PMID- 20046360
TI  - Psychometric properties of the life events checklist-korean version.
AB  - OBJECTIVE: The Life Events Checklist is a brief screening instrument that is used
      for potentially traumatic events such as accidents, disasters, sexual or physical
      assaults, or combat-related exposures. The original English version was recently
      tested for reliability and validity and it showed good psychometric properties,
      and so its use is recommended for the assessment of trauma. METHODS: This study
      investigated the reliability and validity of a Life Events Checklist-Korean
      version in 157 consecutive psychiatric outpatients at a university-affiliated
      teaching hospital. The questionnaire also included the Impact of Events Scale
      Revised (IES-R), the Beck Depression Inventory (BDI), and the State and Trait
      Anxiety Inventory (STAI). Correlation and principal component analyses were
      conducted. RESULTS: The four week test-retest reliability was good and the
      internal consistency was acceptable. In addition, the number of traumatic events
      was significantly correlated with the posttraumatic depressive and anxiety
      symptoms, which demonstrated the convergent validity of the scale. Additionally,
      exploratory factor analysis identified a six-factor structure that explained
      57.2% of the total variance. CONCLUSION: These findings support the reliability
      and validity of the Life Events Checklist-Korean version.

PMID- 20046361
TI  - Is familiality associated with downward occupation drift in schizophrenia?
AB  - OBJECTIVE: Downward occupational drift has been extensively investigated in
      schizophrenia. It is known that certain illness related factors, such as
      severity, affect drift, but the impact of familial factors has not been
      investigated. METHODS: Occupation drift was studied among patients with
      schizophrenia/schizoaffective disorder (SZ/SZA)(n=523) and 130 affected sib pairs
      (ASPs). Drift was analyzed in relation to familiality as well as demographic and
      clinical variables. For comparison one proband (one of the affected siblings)
      from each ASP was selected. Occupation drift was measured in relation to the most
      responsible job held, and with regard to head of the household (HOH) occupation
      status. RESULTS: There was no significant difference between single affected and
      ASP probands in terms of occupational drift from the most responsible job
      (drifted 39.2% and 38% respectively) and with regard to HOH's occupation (drifted
      88% and 82.8% respectively). A significant part of the sample remained unemployed
      in both single affected and ASP samples. Thus, there was no significant impact of
      familiality on these variables. However, marital status, pattern of severity, age
      at onset, gender were found to be associated with downward occupation drift in
      single affected probands while the only significant factor in familial probands
      was pattern of severity of severity when measuring in terms of downward drift
      from most responsible job. CONCLUSION: Though there is occupation drift in
      schizophrenia, there is no detectable impact of familial factors. Employment is
      associated with severity of delete.

PMID- 20046362
TI  - A study of the reliability and validity of the korean version of the penn alcohol
      craving scale for alcohol-dependent patients.
AB  - OBJECTIVE: The Penn Alcohol Craving Scale (PACS) is a stronger predictor of
      subsequent drinking and relapse of alcohol dependence that can be administered
      more quickly and easily than other craving scales. The goal of this study was to
      develop the Korean version of the Penn Alcohol Craving Scale (PACS-K). METHODS:
      To examine the psychometric properties of the PACS-K, responses were chosen from
      80 patients admitted to a treatment facility for alcohol dependence. RESULTS: The
      PACS-K possesses good psychometric properties, as assessed by Cronbach's alpha
      estimates (Cronbach's alpha=0.91). The test-retest reliability of the PACS-K
      showed high correlation (p<0.01) when the retest interval was 1 day. When the
      validity of the PACS-K was investigated using correlation analysis with two other
      craving scales (the Obsessive Compulsive Drinking Scale (OCDS) and the Visual
      Analogue Scale (VAS), high correlations were obtained between total PACS scores
      and total OCDS scores, and between total PACS scores and VAS scores (p<0.01,
      respectively). CONCLUSION: The PACS-K is a reliable and valid measure of alcohol
      cravings, and it could be useful for predicting which individuals are at risk for
      subsequent relapse.

PMID- 20046363
TI  - The Relationship between Alexithymia and General Symptoms of Patients with
      Depressive Disorders.
AB  - OBJECTIVE: Depression has been associated with alexithymic features. However, few
      studies have investigated the differences in the general symptoms of patients
      with depressive disorders according to the presence of alexithymia. Thus, the aim
      of this study was to evaluate the relationship between alexithymia and symptoms
      experienced by patients with clinically diagnosed depressive disorders. METHODS:
      A chart review of patients who were evaluated using the Korean version of the 20
      item Toronto Alexithymia Scale (TAS-20) and Symptom Checklist 90-Revised (SCL-90
      R) at the same time between the years 2003 and 2007 was conducted. A total of 104
      patients with depressive disorders were included and divided into two groups:
      alexithymia (n=52) and non-alexithymia (n=52). A direct comparison between the
      two groups was carried out. Regression analysis was also carried out for the TAS
      20 total and subset scores in order to model the relationship between alexithymia
      and symptoms. RESULTS: The presence of alexithymia was confirmed in 50% of the
      patients with depressive disorders, and the symptoms of depressive patients with
      alexithymia were more severe than those of their non-alexithymic counterparts on
      all 9 symptom domains of the SCL-90-R. Furthermore, regression analysis revealed
      that the presence of alexithymia was positively associated with depression,
      phobic anxiety, and psychoticism but inversely associated with anxiety.
      CONCLUSION: These results suggest that the clinical features of depression are
      partially dependent on the presence of alexithymia. Alexithymic patients with
      depressive disorders are likely to show more severe depressive, psychotic, and
      phobic symptoms. In other words, clinicians should suspect the presence of
      alexithymic tendencies if these symptoms coexist in patients with depressive
      disorders and address their difficulties in effective communication.

PMID- 20046364
TI  - A prospective study on changes in health status following flood disaster.
AB  - OBJECTIVE: We examined changes in general health status, the prevalence of
      depression and post-traumatic stress disorder (PTSD) symptoms, and the existence
      of pre-trauma contributing factors in an agricultural population following a
      massive flood. METHODS: Eighty-three of 160 residents of Garisan-ni, Inje-gun,
      Gangwon-do, were assessed using the Korean version of the 36-Item Short-Form
      Health Survey (SF-36-K) between April and June 2006, just prior to a massive
      flood. Among those initially assessed, 58 residents were available for follow-up
      18 months after the flood. Participants completed the SF-36-K, Beck Depression
      Index (BDI), Minnesota Multiphasic Personality Inventory (MMPI)-PTSD, and the
      Korean version of the Impact of Event Scale-Revised (IES-R) to detect depression
      and PTSD. Trauma experiences were also assessed. Factors related to changes in
      health status were then analyzed. RESULTS: SF-36-K total scale scores decreased
      significantly, suggesting a significant reduction in health-related quality of
      life. The largest reductions were noted in physical and social functioning. Fifty
      three percent of the subjects were at least mildly depressed, and 17% had severe
      depression. In addition, 22% had PTSD on both the IES-R and MMPI-PTSD. Factors
      that contributed to the deterioration of health status following the flood were
      the number of disaster events and existence of depression (as assessed by the
      BDI). CONCLUSION: The flood was found to lead to deterioration of health status
      and to provoke depression and PTSD among the agricultural population in the
      mountainous region. We suggest that the number of disaster event experiences and
      existence of depression contriuted to changes in health status after the flood.

PMID- 20046365
TI  - Serum S100B Levels and Major Depressive Disorder: Its Characteristics and Role in
      Antidepressant Response.
AB  - OBJECTIVE: S100B is a neurotrophic factor that is involved in neuroplasticity.
      Neuroplasticity is disrupted in depression; however, treatment with
      antidepressants can restore neuroplasticity. S100B has previously been used as a
      biological marker for neuropathology and neuroplasticity; therefore, in this
      study, we compared serum S100B levels in depressive patients to those of normal
      controls. In addition, we compared the serum S100B levels of antidepressant
      responders to those of nonresponders. METHODS: Thirty five normal controls and 59
      depressive patients were enrolled in this study. Depressive patients entered a 6
      week clinical trial that included treatment with antidepressants. The serum S100B
      levels and clinical assessments, which included Hamilton depression rating
      scores, were measured at baseline and after 6 weeks of treatment with
      antidepressants. The difference in the serum S100B levels between depressive
      patients and normal controls and between antidepressant responders and
      nonresponders was then compared. RESULTS: There were no significant differences
      in the serum S100B levels of normal controls and depressive patients. In
      addition, 30 of the depressive patients responded to antidepressant treatment
      while 29 did not. Finally, the responders had significantly higher baseline serum
      S100B levels than the nonresponders. CONCLUSION: The results of this study
      suggest that the baseline serum S100B level is associated with the subsequent
      response to antidepressants. In addition, the high baseline serum S100B level
      that was observed in depressive patients may enhance neuroplasticity, which
      results in a favorable therapeutic response to antidepressants.

PMID- 20046366
TI  - Innovations in clinical research design and conduct in psychiatry: shifting to
      pragmatic approaches.
AB  - The classically structured clinical trial does not offer enough flexibility to
      make use of continuously emerging knowledge that is generated as the trial
      progresses. In this regard, there are consistent issues impeding effective
      psychiatric research, including limitations in efficiency, difficulty
      demonstrating significant differences between treatment arms, poor external
      validity, and ethical constraints. For example, research in the field of
      psychiatry shows that it is growing increasingly more challenging to demonstrate
      superiority of interventions to placebo in part related to the increasing placebo
      response rates. Various design innovations and other tricks of the trade have
      surfaced to improve sensitivity towards detecting drug-placebo differences and
      reduce sources of bias in psychiatric research. Diverse strategies have been
      developed to address these obstacles and improve the outcomes of clinical
      research in psychiatry. The current review highlights many of these innovations
      and describes examples of their practical use, mainly focusing on the study
      design and conduct perspectives. In the study design issues, adaptive, equipoise
      stratified, sequential parallel and effectiveness design will be explored. The
      proper strategies for pragmatic and ethical conduction of clinical trials will be
      also discussed in-depth.

PMID- 20046367
TI  - Symptoms to use for diagnostic criteria of hwa-byung, an anger syndrome.
AB  - OBJECTIVE: The aim of this study was to identify the characteristic symptoms
      which can be used for the diagnosis of hwa-byung, a culture-related anger
      syndrome in Korea. METHODS: The symptoms of the Hwa-byung Scale were correlated
      with the Korean versions of the Hamilton Depression Rating Scale (K-HDRS) and the
      State and Trait Anger Inventory (K-STAXI) in 89 patients, who were diagnosed as
      having major depressive disorder, dysthymic disorder, anxiety disorders,
      somatoform disorders, or adjustment disorder according to the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria and who
      had self-labeled hwa-byung. Also, the symptoms of the Hwa-byung Scale were
      correlated with each other. RESULTS: The symptoms of the Hwa-byung Scale which
      were significantly correlated with the state anger of the K-STAXI but not with
      the depressive mood (item 1 of K-HDRS) included feelings of unfairness,
      subjective anger, external anger, heat sensation, pushing-up in the chest, dry
      mouth, and sighing. The symptoms which were significantly correlated with state
      anger and depressed mood included respiratory stuffiness, "haan" and hate. The
      symptoms which were not significantly correlated with depressed mood and state
      anger included going-out, epigastric mass, palpitation, headache/pain,
      frightening easily, many thoughts, and much pleading. These symptoms also showed
      higher correlation with each other in the correlation matrix. CONCLUSION: Our
      findings suggest that hwa-byung is different from depressive syndrome in terms of
      its symptom profile, and suggest what symptoms should be included in the
      diagnostic criteria of hwa-byung, an anger disorder.

PMID- 20046368
TI  - Alexithymia and Stress Response Patterns among Patients with Depressive Disorders
      in Korea.
AB  - OBJECTIVE: Alexithymic characteristics may represent cognitive and affective
      mediators between stressors and stress responses among those with depressive
      disorders. This study evaluated how alexithymic characteristics, as measured by
      the Korean version of the Toronto Alexithymia Scale-20 (TAS-20K), could be
      related to stress response patterns, as measured by the Stress Response Inventory
      (SRI), within a sample composed of individuals diagnosed with depressive
      disorders. METHODS: Participants comprised a cross section of patients diagnosed
      with depressive disorders (n=98). Data on demographic and psychosocial factors
      (i.e., sex, age, and level of education), clinical profiles {i.e., primary and
      comorbid psychiatric conditions meeting the Diagnostic and Statistical Manual of
      Mental Disorders, fourth edition (DSM-IV) criteria at the time of the
      evaluation}, duration of illness, medications, and Clinical Global Impression
      (CGI) scores, and the results of psychological assessments (TAS-20K, SRI) were
      analyzed. RESULTS: Patients having depressive disorders with alexithymia obtained
      significantly higher scores in terms of all seven subscales of the SRI, as
      compared to those without alexithymia, a logistic regression model was used to
      assess possible predictors for the presence of alexithymia in patients with
      depressive disorders, including the seven subscales of the SRI, gender, age, and
      duration of illness. We found that aggressive and somatizing responses to stress
      were significantly associated with the presence of alexithymia among patients
      with depression. CONCLUSION: These findings suggest that patients having
      depression with alexithymia were more susceptible to stress than those without
      alexithymia. Clinicians might improve their treatment of depression by
      identifying the clinical predictors for alexithymia and by helping those
      individuals demonstrating such symptoms in coping with emotionally stressful
      situations.

PMID- 20046369
TI  - Temporal changes in functional magnetic resonance imaging activation of
      heterosexual couples for visual stimuli of loved partners.
AB  - OBJECTIVE: Previous neuroimaging studies on romantic love have focused on
      determining how the visual stimuli that serve as a representation of loved ones
      induce the neural activation patterns of romantic love. The purpose of this study
      was to investigate the temporal changes in romantic love over a period of 6
      months and their correlated neurophysiological changes. METHODS: Five
      heterosexual couples (n=10, mean age 21.1+/-1.97) who started dating not less
      than 100 days previously were recruited to measure their blood oxygen level
      dependent (BOLD) signals using functional magnetic resonance imaging (fMRI) while
      showing them pictures of their loved ones and their previously identified,
      opposite-sex friends. Subsequently, the subjects were scanned under the same
      experimental conditions to assess possible changes in their brain activities
      after 180 days. RESULTS: WE FOUND THAT THEIR PASSIONATE LOVE SCORE (PLS) VALUES
      (M: 118.6+/-9.1, F: 120.2+/-7.0) were significantly reduced after 6 months (M:
      110.8+/-4.0, F: 106.2+/-3.0). Furthermore, significantly increased activations
      were found in the cingulate gyri, inferior frontal gyri, supramarginal gyri,
      etc., after 6 months, whereas the head and tail of the right caudate nucleus were
      deactivated, which is indicative of the inhibition of expression and sensory
      neglect. CONCLUSION: These findings suggest that dynamic neural processes in the
      cortical-subcortical regions are involved in temporal changes in romantic love.

PMID- 20046370
TI  - Deficit in decision-making in chronic, stable schizophrenia: from a reward and
      punishment perspective.
AB  - OBJECTIVE: We compared patients with chronic schizophrenia and normal controls
      with respect to decision-making ability. Measures were implemented to control for
      the participants' intelligence levels as well as to ensure to use of a moderate
      sample size. The goal of this study was to confirm inconsistent results from
      previous studies which had stemmed from too small of a sample size, highly
      variable performance of normal controls, and not controlling for intelligence as
      a confounding factor. METHODS: Fifty-two chronic stable schizophrenic inpatients
      and 55 healthy controls participated in the study. We controlled for intelligence
      by including subjects with intelligence quotient's (IQ) between 80 and 120,
      examining any differences in decision-making performance between groups on the
      Iowa Gambling Task (IGT). We also addressed several issues relating to
      performance on the IGT, such as working memory and clinical symptoms. RESULTS:
      Schizophrenic patients were found to perform poorly on the IGT relative to normal
      controls (F(1,105)=17.73, p<0.001); however, more importantly, they also
      displayed the slow yet profitable shift from disadvantageous decks to
      advantageous decks over time. We also found that when compared with healthy
      controls, schizophrenic patients showed a poorer performance on the Wisconsin
      Card Sorting Test (WCST)(t=-5.48, p<0.001 for perseverative error) which was not
      related to their performance on the IGT. CONCLUSION: Based on previous literature
      and the results of this study, impaired sensitivity to both reward and punishment
      might be a more plausible explanation for the poor performance on the IGT in the
      schizophrenic group. We speculated that this impairment seemed related more to
      the different responsiveness to the magnitude than to the frequency of
      punishment, and to the different interpretation of less informative verbal cues
      in the context of the reinforcing schedule.

PMID- 20046371
TI  - Nocturnal sleep related with metabolic markers in end-stage renal disease
      patients receiving hemodialysis.
AB  - OBJECTIVE: It has been suggested that oxidative stress and inflammation are
      associated with the pathophysiology of sleep disorders in end-stage renal disease
      (ESRD) patients. We examined the relationship of the sleep variables reflecting
      sleep breathing disorder and limb movements during sleep with the clinical
      variables reflecting the metabolic abnormalities in ESRD patients receiving
      hemodialysis. METHODS: Nocturnal polysomnography was conducted in 30 ESRD
      patients (21 men, 9 women), who were receiving hemodialysis. Blood was sampled
      before hemodialysis for each patient in order to measure uric acid (UA), C
      reactive protein (CRP), and interleukin-6 (IL-6). RESULTS: UA was correlated
      positively with the total sleep time (TST)(r=0.407) and negatively with the apnea
      hypopnea index (AHI) and oxygen desaturation index (ODI)(r=-0.377, -405).
      CONCLUSION: CRP was positively correlated with the limb movement index
      (LMI)(r=0.401). Our study showed that increased UA was related to decreased
      respiratory disturbance during sleep in ESRD patients receiving hemodialysis.

PMID- 20046372
TI  - G-protein beta3 Subunit Gene 825C/T Polymorphism Is Not Associated with
      Olanzapine-Induced Weight Gain in Korean Schizophrenic Patients.
AB  - OBJECTIVE: Weight gain is a possible adverse effect of the use of antipsychotics,
      and is an important factor for long-term health and treatment compliance.
      Olanzapine is an atypical antipsychotic known to cause considerable weight gain.
      A relationship between weight gain and the G protein beta3 subunit gene (GNB3)
      825C/T polymorphism has been reported. We therefore examined this possible
      association in a Korean schizophrenic patient group receiving olanzapine
      treatment. METHODS: Weight and height measurements were obtained prior to
      starting olanzapine and measured again after long-term treatment. Genotyping for
      the 825C/T polymorphism was performed using a PCR-based method. RESULTS: We found
      that long-term treatment with olanzapine resulted in mean gains in weight and
      body mass index (BMI) of 5.2 kg and 1.93 kg/m(2), respectively. There was a no
      significant difference in the mean body weight change from baseline to the
      endpoint after olanzapine treatment between the genotype groups (p=0.796). There
      were also no significant differences in genotype or allele frequencies between
      the severe weight-gain (more than 10%) and minimal weight-gain (less than 10%)
      groups (chi(2)=0.037, p=0.98; chi(2)=0.020, p=0.89). CONCLUSION: The finding from
      this study thus does not support a relationship between the GNB3 825C/T
      polymorphism and weight gain in Korean schizophrenic patients receiving
      olanzapine treatment.

PMID- 20046373
TI  - An Association Study of the A218C Polymorphism of the Tryptophan Hydroxylase 1
      Gene with Eating Disorders in a Korean Population: A Pilot Study.
AB  - OBJECTIVE: We examined the association between the tryptophan hydroxylase 1
      (TPH1) gene and eating disorders focusing on obsessionality. METHODS: The sample
      included 62 women with a lifetime diagnosis of anorexia nervosa (AN) as well as
      50 women with a lifetime diagnosis of bulimia nervosa (BN) recruited from
      specialist clinics for eating disorders and 131 healthy women in Korea. Blood
      samples were collected from all participants for the TPH1 genotyping. The
      patients were ad ministered the Korean version of the Eating Disorders
      Examination and obsessionality was conceptualized using measures of persistence,
      harm avoidance, and obsessive-compulsive symptoms. RESULTS: In the case-control
      comparisons, the frequency of the A/A genotype was increased in the patients with
      BN, but this difference was not significant after correcting for multiple
      testing. We found no effect of the TPH A218C polymorphism on obsessionality in
      the patients with AN or BN. CONCLUSION: Although the present findings should be
      regarded as preliminary because of the small size of our sample, they suggest
      that the TPH1 gene may contribute to the genetic susceptibility to BN and be
      associated with the other unexplored traits of bulimic case status.

PMID- 20046374
TI  - The first report of fetal alcohol effect in a 12 year-old child in Korea.
AB  - We present the first report of fetal alcohol effect in a 12 year-old child in
      Korea. The mother had consumed 162 g of alcohol per week continuously during
      pregnancy. His first febrile seizure occurred before he was 1 year old, and
      became more frequent 2 years later. He started showing signs of right paraplegia
      when he was 3.5 years old and brain MRI revealed periventricular leucomalacia
      near the left ventricle. He was microcephalic and his growth was retarded. He was
      irritable, impatient, impulsive, and inattentive, and showed disinterest in
      school activities and aggressive and dangerous behavior. After the diagnosis of
      attention deficit/hyperactivity disorder was made, psychopharmacological
      treatment and family support was initiated. After 10 months, he still had
      intermittent ideas of reference, although the aggressive behavior,
      inattentiveness, and impulsivity had improved. Using this case study, we stress
      the importance of maternal alcohol history in patients with these
      characteristics.

PMID- 20046375
TI  - Does pregabalin have neuropsychotropic effects?: a short perspective.
AB  - Pregabalin is a newly developed synthetic gamma-aminobutyric acid (GABA) that is
      approved for the treatment of fibromyalgia and several neuropathy. It has been
      proven to show analgesic, anxiolytic, anticonvulsant and sleep enhancement
      effects, which could be applicable in the treatment of a variety of psychiatric
      disorders. There have been consistent reports that unexplained somatic symptoms
      (i.e., pain) may be a part of psychiatric disorders such as major depressive
      disorder (MDD) and anxiety disorders. Previous researches have also suggested the
      possible therapeutic potential of anticonvulsants as augmentation therapy or
      monotherapy in the treatment of mood disorders and anxiety disorders. Hence this
      short perspective tries to prompt and facilitate a shifting of researchers'
      attention to potential neuropsychotropic drug role of pregabalin to treat a wide
      range of neuropsychiatric disorders.

PMID- 20046376
TI  - Service priority and standard performance of community mental health centers in
      South Korea: a delphi approach.
AB  - OBJECTIVE: The role of community mental health centers (CMHCs) in Korea is quite
      different than that of these centers in Western countries due to nation-specific
      health care system characteristics. For example, CMHCs of Korea are expected to
      provide services for serious mental illness in addition to other services in
      response to community needs, such as internet addiction of adolescents.
      Consequently, it is important to determine service priorities of CMHCs and to
      define standard service performances in order to maximize their effectiveness
      with limited resources. The present study aimed to generate expert consensus on
      service priorities and to identify standard service performances of CMHCs in
      South Korea. METHODS: Forty-five mental health professionals participated as
      experts in a Delphi survey. We made a survey questionnaire based on Korean and
      international data and guidelines of some countries such as the UK and Australia.
      Experts answered the first and second round questionnaires and their answers were
      analyzed using frequency analysis. RESULTS: For the question about future
      directions of CMHCs, twenty-two experts (49%) answered that the growth of
      services for serious mental illness should be preferred to other areas. The
      service for chronic mental illness was thought to be the most important service
      area (27.1%) and, early psychosis (10.5%) is included, the services for serious
      mental illness should be regarded as the most important service area of Korean
      CMHCs. It is followed by child and adolescent services (13.2%) and mental health
      promotion services (10.8%). The relative importance of service performances on
      each service domain were given by answers of experts. CONCLUSION: CMHCs in Korea
      should focus their priority on the management of serious mental illness. Service
      standardization by the relative importance of service performances on each
      service domain is needed.

PMID- 20046377
TI  - Accept or refuse? A pilot study of patients' perspective on participating as
      imaginary research subjects in schizophrenia.
AB  - OBJECTIVE: The goal of the present study was to evaluate demographic and clinical
      factors that affect the intention to participate in commonly-conducted research
      in patients with schizophrenia. METHODS: Thirty-four outpatients with a diagnosis
      of schizophrenia were enrolled in this study. They were asked whether they would
      have any intention to participate in four imaginary studies: a simple
      questionnaire, a genetic study, a study of complex tasks and a risky study. We
      analyzed the differences in general psychopathology, insight and demographic
      characteristics of the participants according to their responses (acceptance or
      refusal) to the four proposed studies. RESULTS: Younger and better-educated
      patients tended to decline participation in a risky study. Patients with a longer
      duration of regular psychiatric follow-ups tended to willingly participate in the
      simple questionnaire. There were no overall statistical differences in general
      psychopathology and insight between patients who agreed or declined to
      participate in studies. CONCLUSION: Age and education level may be factors that
      influence decisions to participate in schizophrenia studies. Further research is
      needed to confirm and expand on the current findings.

PMID- 20046378
TI  - Anhedonia and ambivalence in schizophrenic patients with fronto-cerebellar
      metabolic abnormalities: a fluoro-d-glucose positron emission tomography study.
AB  - OBJECTIVE: Prefrontal and cerebellar abnormalities have been associated with
      higher cognitive deficits in schizophrenia. The current study aimed to show
      whether or not schizophrenic patients with fronto-cerebellar functional
      abnormalities show more anhedonia or ambivalence. METHODS: Regional cerebral
      metabolic activity was measured using fluoro-D-glucose positron emission
      tomography and was compared between 24 patients with chronic schizophrenia and 22
      healthy normal volunteers. The existence of regional prefrontal hypofunction and
      regional cerebellar hyperfunction was investigated in each patient. Demographic
      and clinical variables including the emotional self-report scales were compared
      between the subgroups of the patients categorized according to the existence and
      the absence of the regional dysfunctions. RESULTS: Comparisons between each
      patient and the total normal controls revealed that 14 of the total twenty-four
      patients had regional hypofrontal functions, whereas 11 patients had regional
      hypercerebellar functions. Patients with prefrontal hypofunction showed more
      severe anhedonia than those without prefrontal hypofunction, whereas patients
      with cerebellar hyperfunction compared to those without cerebellar hyperfunction
      had more severe ambivalence. CONCLUSION: It seems that fronto-cerebellar
      abnormalities may be associated with cardinal emotional features of
      schizophrenia, such as anhedonia and ambivalence.

PMID- 20046379
TI  - Correlates of metabolic abnormalities in bipolar I disorder at initiation of
      acute phase treatment.
AB  - OBJECTIVE: Treatment of bipolar patients is often complicated by metabolic
      abnormalities such as obesity, diabetes, and dyslipidemia. We therefore evaluated
      the prevalence of these abnormalities and their correlates, in bipolar I
      patients, at the time of commencement of pharmacological treatment for acute mood
      episodes. METHODS: The study cohort consisted of 184 bipolar I patients
      hospitalized for treatment of acute mood episodes. Socio-demographic and clinical
      variables were noted and metabolic parameters, including body mass index, fasting
      plasma glucose, fasting total cholesterol, and current treatment(s) for diabetes
      and/or dyslipidemia were measured before initiating medication(s). RESULTS: Fifty
      six (30.4%) subjects met our criteria for obesity; 80 (43.5%) had hyperglycemia,
      with 8 (4.3%) receiving anti-diabetic medication; and 38 (20.7%) had
      hypercholesterolemia, with 2 (1.1%) receiving cholesterol-lowering agents. We
      found that male sex (chi(2)=5.359, p=0.021), depressed or mixed state versus
      manic state (chi(2)=4.302, p=0.038), and duration of illness (t=2.756, p=0.006)
      were significantly associated with obesity. Older age (t=3.668, p<0.001), later
      age of disease onset (t=2.271, p=0.024), and lower level of educational
      attainment (beta=-0.531, p=0.001) were associated with hyperglycemia. CONCLUSION:
      Our finding that metabolic abnormalities are prevalent when initiating acute
      pharmacological treatment in bipolar I patients indicates that these factors
      should be integrated into treatment plans at the onset of disease management.

PMID- 20046380
TI  - Treatment with selective serotonin reuptake inhibitors and mirtapazine results in
      differential brain activation by visual erotic stimuli in patients with major
      depressive disorder.
AB  - OBJECTIVE: The objective of this study was to identify patterns of brain
      activation elicited by erotic visual stimuli in patients treated with either
      Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine. METHODS: Nine
      middle-aged men with major depressive disorder treated with an SSRI and ten
      middle-aged men with major depressive disorder treated with mirtazapine completed
      the trial. Ten subjects with no psychiatric illness were included as a control
      group. We conducted functional brain magnetic resonance imaging (fMRI) while a
      film alternatively played erotic and non-erotic contents for 14 minutes and 9
      seconds. RESULTS: The control group showed activation in the occipitotemporal
      area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate
      nucleus. For subjects treated with SSRIs, the intensity of activity in these
      regions was much lower compared to the control group. Intensity of activation in
      the group treated with mirtazapine was less than the control group but grea-ter
      than those treated with SSRIs. Using subtraction analysis, the SSRI group showed
      significantly lower activation than the mirtazapine group in the anterior
      cingulate gyrus and the caudate nucleus. CONCLUSION: Our study suggests that the
      different rates of sexual side effects between the patients in the SSRI-treated
      group and the mirtazapine-treated group may be due to different effects on brain
      activation.

PMID- 20046381
TI  - Polarity of the first episode and time to diagnosis of bipolar I disorder.
AB  - OBJECTIVE: The current study explored the relationship between the polarity of
      the first episode and the timing of eventual diagnosis of bipolar I disorder, and
      associated clinical implications. METHODS: Twelve years of clinical data from the
      medical records of 258 inpatients meeting DSM-III-R or DSM-IV criteria for
      bipolar I disorder were analyzed. Subjects were divided into two groups according
      to the polarity of the first episode: those with depressive polarity (FE-D), and
      those with manic polarity (FE-M). Comparisons were made between the two groups on
      variables associated with the timing of diagnosis and related outcomes. RESULTS:
      In population with bipolar I disorder, a significant longer time lapse from the
      first major mood episode to the confirmed diagnosis was associated with the FE-D
      group compared to the FE-M group [5.6 (+/-6.1) vs. 2.5 (+/-5.5) years, p<0.001].
      FE-D subjects tended to have prior diagnoses of schizophrenia and major
      depressive disorder while FE-M subjects tended to have prior diagnoses of bipolar
      disorder and schizophrenia. A significantly higher rate of suicide attempts was
      associated with the FE-D group compared to the FE-M group (12.7 vs. 1.7%,
      p<0.001). CONCLUSION: The results of this study indicate that first-episode
      depressive polarity is likely to be followed by a considerable delay until an
      eventual confirmed diagnosis of bipolar I disorder. Given that first-episode
      depressive patients are particularly vulnerable to unfavorable clinical outcomes
      such as suicide attempts, a more systematic approach is needed to differentiate
      bipolar disorder among depressed patients in their early stages.

PMID- 20046382
TI  - AKT1 Gene Polymorphisms and Obstetric Complications in the Patients with
      Schizophrenia.
AB  - OBJECTIVE: We performed a genetic association study with schizophrenic patients
      to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1)
      gene plays a role in obstetric complications. METHODS: One-hundred-eighty
      patients with schizophrenia (male, 113; female, 67) were included. All patients
      fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were
      measured by the Lewis scale. Prenatal and perinatal information was
      retrospectively collected from the patients' mothers. We selected six single
      nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2
      (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA
      (rs2498804). The genotype data were analyzed for an association with the Lewis
      total score in terms of allele, genotype, and haplotype distribution. RESULTS:
      The mean total Lewis scores were 1.30+/-1.61 for males and 1.54+/-1.87 for
      females. Higher total score tended to be correlated with an earlier age of onset
      of schizophrenia in females. In the total sample, no SNP was associated with
      obstetric complications. However, the additional analyses for male and female
      subgroups found a significant association between SNPA and SNP4 and Lewis score
      in females (p=0.02 for SNPA, p=0.04 for SNP4). The SNP5-SNPA haplotype showed a
      positive association with obstetric complications (p=0.03) in the female patient
      group. CONCLUSION: We found an association between SNPs in the AKT1 gene and
      total Lewis score measuring obstetric complications in female patients with
      schizophrenia. Because these findings did not survive a correction for multiple
      testing, the significance should be interpreted carefully and replication studies
      are required.

PMID- 20046383
TI  - No Evidence for Association between Tyrosine Hydroxylase Gene Val81Met
      Polymorphism and Susceptibility to Tardive Dyskinesia in Schizophrenia.
AB  - OBJECTIVE: Tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine
      biosynthesis. Because the TH Val81Met polymorphism is located in the amino
      terminal regulatory domain of the tetrameric enzyme, it is a candidate marker for
      susceptibility to dopamine-related traits. We investigated the hypothesis that TH
      Val81Met polymorphism can influence susceptibility to tardive dyskinesia (TD) in
      schizophrenia. METHODS: TH Val81Met polymorphism was analyzed by PCR-based
      methods in 83 schizophrenic patients with TD and 126 schizophrenic patients
      without TD, matched for antipsychotic drug exposure and other relevant variables.
      RESULTS: There was no significant association of the genotype and allele
      frequencies determined by the TH Val81Met polymorphism between TD and non-TD
      patients. In addition, there was no significant difference in terms of total
      Abnormal Involuntary Movement Scale scores among the three genotype groups.
      CONCLUSION: Within the limitations imposed by the size of the clinical sample,
      these findings suggest that the Val81Met polymorphism of the TH gene does not
      contribute significantly to the risk for TD.

PMID- 20046384
TI  - Major depressive disorder preceding the onset of progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized
      by vertical supranuclear palsy and parkinsonian symptoms. The neuropsychiatric
      symptoms of PSP include anhedonia, depressed mood and cognitive impairment.
      Patients with PSP have an increased risk for developing depressive disorders
      within the next year. However, it is rare to find that major depressive disorder
      was the antecedent diagnosis of a patient who was later diagnosed with PSP. We
      present here a patient who suffered from PSP with repetitive falls, a masked face
      and dysarthria after developing a major depressive disorder.

PMID- 20046385
TI  - Virtual reality for obsessive-compulsive disorder: past and the future.
AB  - The use of computers, especially for virtual reality (VR), to understand, assess,
      and treat various mental health problems has been developed for the last decade,
      including application for phobia, post-traumatic stress disorder, attention
      deficits, and schizophrenia. However, the number of VR tools addressing obsessive
      compulsive disorder (OCD) is still lacking due to the heterogeneous symptoms of
      OCD and poor understanding of the relationship between VR and OCD. This article
      reviews the empirical literatures for VR tools in the future, which involve
      applications for both clinical work and experimental research in this area,
      including examining symptoms using VR according to OCD patients' individual
      symptoms, extending OCD research in the VR setting to also study behavioral and
      physiological correlations of the symptoms, and expanding the use of VR for OCD
      to cognitive-behavioral intervention.

PMID- 20046386
TI  - Prevalence and Correlates of Depressive Symptoms among North Korean Defectors
      Living in South Korea for More than One Year.
AB  - OBJECTIVE: This study examined the prevalence and correlates of depressive
      symptoms in North Korean defectors who have been living in South Korea for more
      than one year. METHODS: We used questionnaires developed by the authors to
      collect sociodemographic data in addition to the Center for Epidemiologic Studies
      Depression Scale (CES-D), the Psychosocial Well-being Index to measure stress,
      and a social support scale. A total of 367 subjects were included in this study.
      RESULTS: The results showed that 30.5% of the men and 34.7% of the women reported
      depressive symptoms, and 33.1% of the men and 36.1% of the women exhibited signs
      of severe distress. Correlates of depressive symptoms were lack of occupation
      [odds ratio (OR)=2.198, 95% confidence interval (CI), 1.247-3.873], having
      escaped without family (OR=1.725, 95% CI, 1.006-2.959), and a poor subjective
      sense of health status (OR=3.111, 95% CI, 1.591-6.085). CONCLUSION: Continuing
      vocational training and career management, psychological support programs, and
      intensive physical health services are needed to improve the mental health of
      this population.

PMID- 20046387
TI  - The effect of the traditional living arrangement, anpakkori, on depressive
      symptoms in elderly people residing on jeju island.
AB  - OBJECTIVE: We examined the effect of anpakkori, a traditional living arrangement,
      on depression among elderly people on Jeju Island in Korea. METHODS: A total of
      593 subjects were assessed using a sociodemographic questionnaire developed by
      the authors, the Korean version of Geriatric Depression Scale (KGDS), the Social
      Support Scale, and the Activities of Daily Living/Instrumental Activities of
      Daily Living scales (ADL/IADL). Subjects were classified into three groups: those
      residing with their adult children, those living individually, and those living
      in the traditional Jeju anpakkori living arrangement. RESULTS: The prevalence of
      depression in this study was 53.1%, and the traditional Jeju living arrangement,
      anpakkori, was significantly correlated with the presence of depressive symptoms
      (p=0.005)[odds ratio (OR)=1.88, 95% confidence interval (CI)=1.16-3.06].
      CONCLUSION: Living in the traditional Jeju way may not be as good for
      establishing family solidarity as is living with adult children. Moreover,
      elderly individuals prone to depression tended to live in this anpakkori living
      arrangement. Careful psychological and social support systems that might prevent
      the development of depressive symptoms should be provided for those who live in
      anpakkori living arrangements.

PMID- 20046388
TI  - A Comparative Study of Involvement and Motivation among Casino Gamblers.
AB  - OBJECTIVE: The purpose of this paper is to investigate three different types of
      gamblers (which we label "non-problem", "some problem", and "probable
      pathological gamblers") to determine differences in involvement and motivation,
      as well as differences in demographic and behavioral variables. METHODS: The
      analysis takes advantage of a unique opportunity to sample on-site at a major
      casino in South Korea, and the resulting purposive sample yielded 180 completed
      questionnaires in each of the three groups, for a total number of 540. Factor
      analysis, analysis of variance (ANOVA) and Duncan tests, and Chi-square tests are
      employed to analyze the data collected from the survey. RESULTS: Findings from
      ANOVA tests indicate that involvement factors of importance/self-expression,
      pleasure/interest, and centrality derived from the factor analysis were
      significantly different among these three types of gamblers. The "probable
      pathological" and "some problem" gamblers were found to have similar degrees of
      involvement, and higher degrees of involvement than the non-problem gamblers. The
      tests also reveal that motivational factors of escape, socialization, winning,
      and exploring scenery were significantly different among these three types of
      gamblers. When looking at motivations to visit the casino, "probable
      pathological" gamblers were more likely to seek winning, the "some problem" group
      appeared to be more likely to seek escape, and the "non-problem" gamblers
      indicate that their motivations to visit centered around explorations of scenery
      and culture in the surrounding casino area. CONCLUSION: The tools for exploring
      motivations and involvements of gambling provide valuable and discerning
      information about the entire spectrum of gamblers.

PMID- 20046389
TI  - Comparison of Clinical Features and Personality Dimensions between Patients with
      Major Depressive Disorder and Normal Control.
AB  - OBJECTIVE: Personality dimension is considered as a risk factor of depression.
      This study was to compare aggression, impulsivity, hopelessness, and TCI
      (temperament and character dimensions) between patients with major depressive
      disorder (MDD) and normal controls. METHODS: A total of 56 MDD patients and the
      same number of normal controls who were matched for age, gender, and education
      were recruited. All subjects completed the following questionnaires; Aggression
      Questionnaire (AQ), Beck Hopelessness Scale (BHS), Barratt Impulsiveness Scale,
      11th Version (BIS-11), and Temperament and Character Inventory (TCI). RESULTS:
      MDD patients were significantly higher scores in anger, hostility of AQ, BHS,
      motor impulsivity of BIS-11, and Harm Avoidances (HA) of TCI with all subscales
      of HA than normal controls, whereas novelty seeking 1 (NS1) (Exploratory of NS),
      Reward Dependence (RD) with RD3 (Attachment) . RD4 (Dependence), Self
      Directedness (SD) with most subscales of SD, Cooperativeness (CO), and ST3
      (Spiritual Acceptance) showed lower scores than normal controls. Moreover, BHS
      and HA, BIS and NS showed moderate positive correlation in MDD patients, while
      BHS and SD, HA and SD were negatively correlated. CONCLUSION: The present study
      showed unique clinical features, especially personality dimensions of patients
      with MDD. Our results could be applicable to suggest treatment process and to
      predict one's prognosis for depression in that psychological properties are
      important for drug compliance and treatment response.

PMID- 20046390
TI  - The impact of executive function on emotion recognition and emotion experience in
      patients with schizophrenia.
AB  - OBJECTIVE: This study investigated the impact of executive function on the
      performance of two different affective tasks, the Facial Affect Identification
      Task (FAIT) and the Iowa Gambling Task (IGT), in patients with schizophrenia.
      METHODS: Thirty-nine patients with schizophrenia and 33 healthy controls
      completed the FAIT and the IGT, followed by the Wisconsin Card Sorting Test
      (WCST) and the intelligence quotient (IQ) test. In addition to correlation
      analysis, regression analysis was used to determine the extent to which the
      performance of the WCST, in particular, perseverative error (PE), accounted for
      the variation in both the FAIT and the IGT. RESULTS: Relative to normal controls,
      patients with schizophrenia showed significant impairments in the IGT, the FAIT
      and the WCST even after controlling for IQ. While normal controls did not show
      any relationships between the WCST and two affective tasks, patients with
      schizophrenia showed that variables in the WCST correlated not only with the FAIT
      total correct score (r=-0.503, p=0.001 for PE) but also with the IGT net score
      (r=0.385, p=0.016 for PE). The PE score was a better predictor of the performance
      on the FAIT (R(2)=0.25) than that of the performance on the IGT (R(2)=0.15).
      CONCLUSION: Our findings imply that deficits in executive function in
      schizophrenia can affect performance on facial emotion recognition task more than
      performance on task based on emotion experience, that is, the feedback from the
      body. Therefore, more consideration is needed of the impact of executive function
      when interpreting the result of "conventional" facial affect recognition tests as
      opposed to interpreting the IGT.

PMID- 20046391
TI  - The Korean Version of the Adolescent Dissociative Experience Scale: Psychometric
      Properties and the Connection to Trauma among Korean Adolescents.
AB  - OBJECTIVE: The Adolescent Dissociative Experience Scale (A-DES) is a screening
      measure for dissociative experience in adolescents. The present study aimed to
      investigate the reliability, validity and psychometric properties of the Korean
      version of the Adolescent Dissociative Experience Scale. METHODS: The Korean
      version of the A-DES was administered to a normative group of 371 adolescents
      aged 12 to 18 years and a traumatized group of 33 adolescents aged 12 to 18 years
      with known trauma. RESULTS: The internal consistency was excellent (Cronbach's
      alpha=0.91) and the test-retest correlation of the A-DES was high (r=0.99).
      Correlation between the A-DES and other measures of dissociation was moderate
      (r=0.48). There were no significant age differences in mean total A-DES scores
      for the normative sample, or for boys or girls separately. Nor were there any
      significant gender differences for any age group. The mean total score of the A
      DES was significantly higher in the traumatized group than in the normative
      group. There was a statistically significant difference between adolescents with
      self-reported trauma and those without a trauma history in the normative group.
      CONCLUSION: This study demonstrated that the Korean version of the A-DES is a
      reliable measure with excellent internal consistency and good stability over a 4
      week test-retest interval with single factor structure. It can be used to screen
      for dissociative symptoms in Korean adolescents between the ages 12 and 18.

PMID- 20046392
TI  - Reliability and validity of the 20-item toronto alexithymia scale in korean
      adolescents.
AB  - OBJECTIVE: Adolescence is a period of developing emotional regulation. However,
      alexithymia has rarely been examined during this period. The objective of this
      study is to examine the factor structure and internal consistency of the Korean
      version of the 20-item Toronto Alexithymia Scale (TAS-20K) in normal adolescents
      in South Korea. METHODS: The TAS-20K was administered to a sample of 290
      adolescents aged from 12 to 16 years old. Internal reliability, test-retest
      reliability, and factorial validity were evaluated. RESULTS: The three factors of
      the TAS-20K were confirmed by confirmatory factor analysis. The internal
      consistency, measured using Cronbach's alpha coefficient was acceptable for
      difficulty in identifying feelings, good for difficulty in describing feelings,
      and acceptable for externally oriented thinking. CONCLUSION: Our study indicates
      that the TAS-20K is an appropriate instrument to assess alexithymia in Korean
      adolescents.

PMID- 20046393
TI  - Impairment of instrumental activities of daily living in patients with mild
      cognitive impairment.
AB  - OBJECTIVE: THIS STUDY WAS CONDUCTED TO EXAMINE THE FOLLOWING: whether patients
      with mild cognitive impairment (MCI) show impairments in instrumental activities
      of daily living (IADL) as compared to controls; to identify the functional sub
      domains of instrumental activities of daily living (IADL) that are affected in
      MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living
      (S-IADL) scale cut-off score that best differentiated between MCI and controls.
      METHODS: This study was carried out at the geropsychiatry clinic, university
      hospital. The study participants included 66 patients with MCI and 61 normal
      elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were
      administered to the main caregivers of all participants in order to assess
      everyday functioning. RESULTS: The total S-IADL score was significantly higher in
      the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean
      (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly
      worse on IADLs, such as the ability to use the telephone, prepare meals, take
      medication, manage belongings, keep appointments, talk about recent events, and
      perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well
      between patients with MCI and controls (Area Under Curve=87%). CONCLUSION: The
      patients with MCI showed impairments in the ability to perform complex ADL in
      comparison to healthy controls. IADLs related to memory and frontal/executive
      functioning were particularly affected in MCI.

PMID- 20046394
TI  - Economic Evaluation of Add-on Levetiracetam for the Treatment of Refractory
      Partial Epilepsy in Korea.
AB  - OBJECTIVE: This study estimated the expected cost-effectiveness ratio expressed
      as the incremental cost per seizure-free day (SFD) gained and the incremental
      cost per quality adjusted life year (QALY) gained when using levetiracetam (LEV)
      as add-on therapy from a third-party payer perspective. METHODS: A 1-year dose
      escalation decision-tree model comparing LEV plus standard therapy (ST) with ST
      alone was designed to combine transition probabilities, costs and outcomes. The
      short-term outcomes and probabilities were derived from a prospective, open-label
      clinical trial with 100 Korean adults with refractory partial epilepsy. All data
      for the direct medical costs were derived from Korean cost data extracted from
      reports published by the National Health Insurance Corporation. RESULTS: The
      average gain in SFDs attributed to LEV add-on was 18.3 days per patient per year
      and the incremental cost-effectiveness ratios (ICERs) for LEV add-on were US$ 44
      per SFD per patient and US$ 11,084 per QALY gained. All sensitivity analyses
      showed that the model was robust to the assumptions made. CONCLUSION: The
      economic evaluation indicates that, given a wide range of assumptions, the
      increased cost of treating patients having refractory partial epilepsy with LEV
      may be partially offset by a reduction in other direct medical costs. This
      reduction is a consequence of an increase in the number of SFDs and improved
      quality of life.

PMID- 20046395
TI  - Plasma concentration of prolactin, testosterone might be associated with brain
      response to visual erotic stimuli in healthy heterosexual males.
AB  - OBJECTIVE: Many studies have showed that excess or lack of sexual hormones, such
      as prolactin and testosterone, induced the sexual dysfunction in humans. Little,
      however, is known about the role of sexual hormones showing normal range in,
      especially, the basal state unexposed to any sexual stimulation. We hypothesized
      sexual hormones in the basal state may affect sexual behavior. METHODS: We
      investigated the association of the sexual hormones level in the basal hormonal
      state before visual sexual stimulation with the sexual response-related brain
      activity during the stimulation. Twelve heterosexual men were recorded the
      functional MRI signals of their brain activation elicited by passive viewing
      erotic (ERO), happy-faced (HA) couple, food and nature pictures. Both plasma
      prolacitn and testosterone concentrations were measured before functional MR
      scanning. A voxel wise regression analyses were performed to investigate the
      relationship between the concentration of sexual hormones in basal state and
      brain activity elicited by ERO minus HA, not food minus nature, contrast.
      RESULTS: The plasma concentration of prolactin in basal state showed positive
      association with the activity of the brain involving cognitive component of
      sexual behavior including the left middle frontal gyrus, paracingulate/superior
      frontal/anterior cingulate gyri, bilateral parietal lobule, right angular,
      bilateral precuneus and right cerebellum. Testosterone in basal state was
      positively associated with the brain activity of the bilateral supplementary
      motor area which related with motivational component of sexual behavior.
      CONCLUSION: Our results suggested sexual hormones in basal state may have their
      specific target regions or network associated with sexual response.

PMID- 20046396
TI  - The effects of galantamine hydrobromide treatment on dehydroepiandrosterone
      sulfate and cortisol levels in patients with chronic fatigue syndrome.
AB  - OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in
      chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A
      functional deficiency of cholinergic neurotransmission may cause the hypothalamic
      pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the
      alterations in stress hormones such as cortisol and dehydroepiandrosterone
      sulfate (DHEAS) in CFS patients before and after 4-week administration of
      galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed
      to investigate whether there are any relationships between the probable hormonal
      changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS
      were measured in 29 untreated CFS patients who were diagnosed according to
      Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the
      patient group, four weeks after 8 mg/d galantamine hydrobromide treatment,
      cortisol and DHEAS levels were measured again. After the treatment 22 patients
      who stayed in study were divided into two subgroups as responders and
      nonresponders according to the reduction in their Newcastle Research Group ME/CFS
      Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre
      and post-treatment cortisol levels and in all CFS patients compared to controls
      (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and
      higher DHEAS/cortisol molar ratios which were normalized following four weeks'
      treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group
      (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of
      the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing
      with galantamine treatment may give some support to the cholinergic deficit
      hypothesis in CFS.

PMID- 20046397
TI  - Association between Antipsychotics-Induced Restless Legs Syndrome and Tyrosine
      Hydroxylase Gene Polymorphism.
AB  - OBJECTIVE: Restless legs syndrome (RLS) has been reported to be more prevalent in
      schizophrenic patients who take antipsychotics. The cause of RLS is unknown but
      associated with dopaminergic deficiency. Tyrosine hydroxylase (TH) is the enzyme
      responsible for catalyzing the conversion of L-tyrosine to DOPA. The purpose of
      this study is to determine whether the TH gene Val81Met polymorphism is
      associated with antipsychotic-induced RLS. METHODS: One hundred ninety Korean
      schizophrenic patients were evaluated by the diagnostic criteria of the
      International RLS Study Group (IRLSSG). The genotyping was performed by PCR-based
      methods. RESULTS: Of the one hundred ninety schizophrenic patients, 44 (23.2%)
      were found to have RLS. Although there were no significant associations between
      TH genotypes or allele frequencies and RLS, when separate analyses were performed
      by sex (male or female), we detected significant differences in the frequencies
      of the genotype (chi(2)=6.15, p=0.046) and allele (chi(2)=4.67, p=0.031) of the
      TH gene Val81Met polymorphism between those with and without RLS in the female
      patients. CONCLUSION: These findings suggest that the TH gene Val81Met SNP might
      be associated with antipsychotic-induced RLS in female schizophrenic patients.

PMID- 20046398
TI  - Association between Dopamine D4 Receptor Gene Polymorphism and Scores on a
      Continuous Performance Test in Korean Children with Attention Deficit
      Hyperactivity Disorder.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between a
      variable number of tandem repeats polymorphism at the dopamine D4 receptor gene
      (DRD4) and the performance of children with attention deficit hyperactivity
      disorder (ADHD) in a continuous performance test (CPT). METHODS: This study
      included 72 ADHD children (mean age=9.39+/-2.05 years) who were recruited from
      one child psychiatric clinic. The omission errors, commission errors, reaction
      time and reaction standardization in the CPT were computed. The number of 48-base
      pairs tandem repeats in the exon III of DRD4 was analyzed in a blind manner.
      RESULTS: The homozygosity of the 4-repeat allele at DRD4 was significantly
      associated with fewer commission errors (t=2.364, df=28.685, p=0.025) and
      standard deviation of reaction time (t=2.351, df=24.648, p=0.027) even after
      adjusting for age. The results of analyses of CPT measured values among three
      groups showed that the group with higher frequency of the 4-repeat allele showed
      a lower mean score of commission errors (F=4.268, df=2, p=0.018). CONCLUSION:
      These results suggest a protective role of 4-repeat allele of the DRD4
      polymorphisms on commission errors in the CPT in children with ADHD.

PMID- 20046399
TI  - Genetic polymorphisms in dopamine- and serotonin-related genes and treatment
      responses to risperidone and perospirone.
AB  - We investigated the possible association between genetic polymorphisms in the
      dopamine receptor and serotonin transporter genes and the responses of
      schizophrenic patients treated with either risperidone or perospirone. The
      subjects comprised 27 patients with schizophrenia who were clinically evaluated
      both before and after treatment. The genotyping of the polymorphisms of the
      dopamine D2 receptor gene (DRD2) (rs1801028 and rs6277), the dopamine D4 receptor
      gene (DRD4) (120-bp tandem repeats and rs1800955), and serotonin transporter gene
      (5HTT)(variable number of tandem repeats; VNTR) were performed using the real
      time polymerase chain reaction and sequencing. In DRD2 and 5HTT-VNTR, there were
      no significant correlations between clinical response and polymorphism in the
      case of risperidone, and for perospirone treatment it was impossible to analyze
      the clinical evaluation due to the absence of genotype information. On the other
      hand, in DRD4 there were significant correlations in the two-factor interaction
      effect on the Positive and Negative Syndrome Scale (PANSS) between the two drugs
      [120-bp tandem repeat, p=0.003; rs1800955, p=0.043]. Although the small sample
      represents a serious limitation, these results suggest that variants in DRD4 are
      a predictor of whether treatment will be more effective with risperidone or with
      perospirone in individual patients.

PMID- 20046400
TI  - Psychiatric disorder in two siblings with hallervorden-spatz disease.
AB  - Hallervorden-Spatz disease (HSD) is a rare autosomal-recessive hereditary
      disorder characterized by the early onset of progressive movement alterations,
      including dystonia, rigidity, choreoathetosis, and mental deterioration. HSD is
      also associated with a variety of psychiatric symptoms, primarily depression and
      mental deterioration. However, psychosis has rarely been reported as a major
      symptom of HSD. We report two siblings who presented psychiatric symptoms as
      major clinical presentations, accompanied by ataxic and spastic gait, dysarthria,
      and typical neuroimaging findings of HSD. A 14-year-old girl presented complex
      motor tics, stereotypic behavior and anxiety symptoms. Her older brother, a 16
      year-old boy, presented prominent auditory hallucinations, persecutory delusions
      and social withdrawal symptoms. Psychiatric symptoms were improved after atypical
      antipsychotic treatment. HSD is a rare disease but should be carefully considered
      in the diagnosis of patients with both motor disorder and various psychiatric
      symptoms.

PMID- 20046401
TI  - A case of galactorrhea associated with excitalopram.
AB  - Escitalopram is one of the most popular selective serotonin reuptake inhibitors
      (SSRIs) in current use as a first-line treatment for depression. Escitalopram is
      well-tolerated and rarely associated with serious side effects. Endocrine and
      reproductive side effects of serotonergic antidepressants are uncommon and
      galactorrhea is very rarely mentioned among SSRI-related side effects. Serotonin
      enhancing antidepressants may result in a rise in prolactin levels through
      suppression of dopamine neurotransmission. In the present study, we report a case
      of hyperprolactinemic galactorrhea associated with escitalopram. A 36-year-old
      woman developed galactorrhea after initiation of escitalopram for depression and
      was found to have an elevated prolactin level. Escitalopram was discontinued with
      resolution of the patient's galactorrhea and normalization of her prolactin
      level.

PMID- 20046402
TI  - Divided countries, divided mind 1: psycho-social issues in adaptation problems of
      north korean defectors.
AB  - A review of studies on the adaptation problems of North Korean defectors in South
      Korean society and studies of people's adaptation to political and cultural
      changes in other countries suggests that similar adaptation problems may occur in
      the process of and after unification. Defectors have various adaptation problems
      and some of them have psychiatric disorders such as depression and post-traumatic
      stress disorder (PTSD). The reasons for this were revealed to be the difference
      in the culture and personality between South and North Korea, which have
      developed for the last 60 years without any communication with each other, in
      spite of their common racial and cultural heritage. Economic factors including
      the lack of skills and knowledge for working at industrialized and competitive
      society like South Korean society, also aggravate the severity of such adaptation
      problems. Research on defectors' adaptation problems and on the differences in
      the culture and mentality between North and South Korea can provide useful
      information on what kinds of problems may arise during the process of and after
      unification and what should be done to achieve mutual adaptation and harmonious
      and peaceful unification.

PMID- 20046403
TI  - Improving access to mental health services for korean american immigrants: moving
      toward a community partnership between religious and mental health services.
AB  - Korean Americans (KAs) with psychiatric service needs underutilizes the
      mainstream mental health services in United States (US). Barriers to mental
      health service access among KAs reflect their unique heritage and culture. More
      than two-thirds of KAs identify themselves as Christians, and Korean clergy have
      influential roles in daily lives of vast majority of KAs. By working with the
      Korean clergy, a small voluntary organization such as the Association of Korean
      American Psychiatrists could provide invaluable assistance in removing the
      barriers to mental health services for KAs.

PMID- 20046405
TI  - Gender differences in suicidal behavior in Korea.
AB  - OBJECTIVE: To examine gender differences in the characteristics of suicidal
      behavior in South Korea. METHODS: Between August 2003 and December 2006, 344
      suicide attempters (116 men, 228 women) participated in this study. The
      attempters were interviewed using the Structured Clinical Interview for DSM-IV
      Axis I Disorders (SCID-I), and the lethality of the attempt was measured using
      the Lethality Suicide Attempt Rating Scale-II (LSARS-II) and Risk-Rescue Rating
      Scale (RRRS). RESULTS: Significantly more women than men were admitted to
      emergency rooms due to attempted suicide during the study period. The male
      attempters were older and had a higher rate of employment than the females.
      Depression was the most common psychiatric disorder in both genders. The
      lesion/toxicity scores of the RRRS indicated that the male suicide attempters
      used higher doses or more toxic agents than the female attempters. The most
      common methods of suicide were ingestion and cutting in both sexes. Although
      there were significant gender differences in the RRRS risk score and RRRS total
      scores, there was no gender difference in the LSARS-II scores, which suggests
      that patients of both sexes share a similar ambivalence regarding suicide
      completion or death. CONCLUSION: Our study should be understood within the
      context of the specific cultural background of South Korea. We found that males
      and females use similar methods when attempting suicide and share a similar
      ambivalence regarding the outcome of the attempt; however, there was a difference
      in severity of the attempt between the two groups. Our findings may aid in the
      identification of more effective methods of intervention to prevent suicide.

PMID- 20046404
TI  - Biological studies on alcohol-induced neuronal damage.
AB  - Alcohol is a well-known cytotoxic agent which causes various kinds of neuronal
      damage. In spite of thousands of published studies, the true mechanism of alcohol
      induced neuronal damage remains unclear. Neurogenesis is the generation of
      neurons from neural stem cells (NSCs) and occurs in predominantly two regions of
      the brain, the subventricular zone and the dentate gyrus of the hippocampus. NSCs
      are the self-renewing, multipotent precursor cells of neurons, astrocytes, and
      oligodendrocytes in the central nervous system. Recent studies have begun to
      illuminate the role of neurogenesis in the biological and cellular basis of
      psychiatric disorders and several clinical symptoms seen in alcoholism such as
      depression, cognitive impairment, underlying stress and brain atrophy have been
      linked to impaired neurogenesis. Heavy alcohol consumption decreases neurogenesis
      in animals, while in vitro studies have shown decreased generation of new neurons
      after alcohol exposure. These findings suggest that decreased neurogenesis is
      important in the pathophysiology of alcoholism. Neurogenesis can be divided into
      four stages; proliferation, migration, differentiation and survival. Our in vitro
      studies on NSCs showed that alcohol decreased neuronal differentiation at doses
      lower than those that affected cell survival and suggested that neuron
      restrictive silencer factor, or repressor element-1 silencing transcription
      factor (NRSF/REST) could be involved in alcohol-induced inhibition of neuronal
      differentiation. In an animal model of fetal alcohol effects behavioral symptoms
      improved after NSC transplantation. Neurogenesis could be the target for new
      strategies to treat alcohol related disorders.

PMID- 20046406
TI  - Folate, vitamin b(12), and homocysteine as risk factors for cognitive decline in
      the elderly.
AB  - OBJECTIVE: Cross-sectional studies have shown that the dysregulation of one
      carbon metabolism is associated with cognitive impairment. However, the findings
      of longitudinal studies investigating this association have been inconsistent.
      This study investigated the prospective associations between cognitive decline
      and the levels of folate, vitamin B(12) and homocysteine both at baseline and
      over course of the study period. METHODS: A total of 607 (83%) elderly
      individuals were selected from a group of 732 elderly individuals without
      dementia at baseline and followed over a 2.4-year study period. The Mini-Mental
      State Examination (MMSE) was administered to the subjects, and the serum levels
      of folate, vitamin B(12) and homocysteine were assayed both at baseline and at
      follow-up examinations. Covariates included demographic data, disability,
      depression, alcohol consumption, physical activity, vascular risk factors, serum
      creatinine level, vitamin intake, and apolipoprotein E genotype. RESULTS:
      Cognitive decline was associated with decreasing quintiles of folate at baseline,
      a relative decline in folate and an increase in homocysteine across the two
      examinations after adjustment for relevant covariates. CONCLUSION: These results
      suggest that folate and homocysteine are involved in the etiology of cognitive
      decline in the elderly.

PMID- 20046407
TI  - An association study of the signal transducer and activator of transcription 6
      gene with periodic psychosis.
AB  - OBJECTIVE: Recent molecular and genetic investigations have suggested that the
      current nosology for major psychiatric disorders, based on the "two-entities
      principal" is not accurate with respect to clinical observations; patient groups
      that do not fit to the current operative diagnostic boundaries are readily
      identified. We aimed to perform an investigation of the signal transducer and
      activator of transcription 6 (STAT6) gene (located on 12q13), which has an
      important role in the apoptotic cascade, with patients suffering from periodic
      psychosis. METHODS: Genetic association study has been employed for the current
      work. Investigated six tag-SNPs were chosen from Hapmap database. RESULTS: Among
      six tag-SNPs, one marker (rs10783813), located in the STAT6 gene, showed modest
      association (p<0.05), although no marker or haplotype block showed association
      after Bonferroni's correction. CONCLUSION: Future studies will reveal the
      etiological role of STAT6, and of other genes of the apoptotic cascade, in major
      psychiatric disorders.

PMID- 20046408
TI  - Comparison of low resolution electromagnetic tomography imaging between subjects
      with mild and severe obstructive sleep apnea syndrome: a preliminary study.
AB  - OBJECTIVE: The purpose of this study was to identify the regions of the brain
      associated with recurrent nocturnal chronic hypoxic episodes in patients with
      untreated obstructive sleep apnea syndrome (OSAS) using low-resolution
      electromagnetic tomography (LORETA) and quantitative electroencephalography
      (QEEG). METHODS: Nocturnal polysomnograph (NPSG) and subsequent morning
      electroencephalograph (EEG) were measured in 20 subjects with OSAS. Mild (n=10
      ages 39.5+/-12.1 years) and severe (n=10 ages 41.7+/-13.6 years) right-handed
      male OSAS subjects were selected by interview and questionnaires including the
      NPSG, Beck Depression Inventory, Beck Anxiety Inventory, Epworth Sleepiness
      Scale, and Pittsburgh Sleep Quality Index. The LORETA and QEEG were compared
      between the severe and mild OSAS groups by frequency bands (delta 1-3 Hz, theta 4
      7 Hz, alpha 8-12 Hz, beta1 13-18 Hz, beta2 19-21 Hz, beta3 22-30 Hz, and total 1
      30 Hz) made by spectral analysis during resting with the eyes closed. RESULTS:
      The LORETA analysis showed decreased alpha activity at the right posterior
      cingulate gyrus (Brodmann area 23) in cases with severe OSAS compared to mild
      OSAS (p<0.05). For the QEEG, the absolute power of the alpha activity (8-12 Hz)
      was decreased in P3 (p=0.047), PZ (p=0.039) and O2 (p=0.04) in cases with severe
      OSAS compared to mild OSAS cases. The LORETA and QEEG analyses had similar
      results with regard to band, activation and location. CONCLUSION: The decreased
      activity of the alpha frequency in the right posterior cingulate gyrus, in
      patients with severe OSAS compared to those with mild OSAS, suggests that chronic
      repeated short-term hypoxia during sleep, in OSAS, could provoke cortical brain
      dysfunction associated with cognitive dysfunction such as memory and attention.

PMID- 20046409
TI  - Dysfunction of the Left Dorsolateral Prefrontal Cortex is Primarily Responsible
      for Impaired Attentional Processing in Schizophrenia.
AB  - OBJECTIVE: The results for finding the deficit in the anterior cingulate (ACC) in
      schizophrenic patients (SZ) have been inconsistent according to the studies that
      used different Stroop tasks, which is unlike the deficit in the dorsolateral
      prefrontal cortex (DLPFC). In order to explore for the core region that's
      responsible for the selective attention deficit in SZ, we examined the results of
      a functional neuroimaging study, which involved the performance of the Stroop
      task using high or low prefrontal cortex related loads in SZ. METHODS: Ten
      schizophrenic patients and healthy controls (HC) received functional magnetic
      resonance imaging (fMRI) during a Short/Long-term latency Stroop task. The
      changes in the neural activity were determined in well-known Stroop related
      regions of interest (ROIs) that consisted of the DLPFC, ACC, the parietal lobule
      and in the whole brain regions for both the main and interaction effects of
      latency, and the results of the short-term and long-term latency Stroop
      conditions were compared. RESULTS: The response times for both the congruency and
      latency effects were more prolonged in the schizophrenics than in the HC. For the
      congruency effect, the schizophrenics showed significantly less activation in the
      same site of the left DLPFC in both the short-term and long-term latency
      conditions, as compared with the HC. For the latency effect, the regions of the
      left-side language network were over- or under-activated in the schizophrenics,
      as compared with the HC. Any interaction effect was not found for both the
      behavioral and fMRI results. CONCLUSION: Our results indicate that the deficit in
      the left DLPFC is the core impairment of attentional processing in
      schizophrenics, regardless of other possible interactions such as the latency
      effect.

PMID- 20046410
TI  - Eye movement desensitization and reprocessing for adolescent depression.
AB  - While cognitive behavior therapy is considered to be the first-line therapy for
      adolescent depression, there are limited data on whether other psychotherapeutic
      techniques are also effective in treating adolescents with depression. This
      report suggests the potential application of eye movement desensitization and
      reprocessing (EMDR) for treatment of depressive disorder related, not to trauma,
      but to stressful life events. At present, EMDR has only been empirically
      validated for only trauma-related disorders such as posttraumatic stress
      disorder. Two teenagers with major depressive disorder (MDD) underwent three and
      seven sessions of EMDR aimed at memories of stressful life events. After
      treatment, their depressive symptoms decreased to the level of full remission,
      and the therapeutic gains were maintained after two and three months of follow
      up. The effectiveness of EMDR for depression is explained by the model of
      adaptive information processing. Given the powerful effects observed within a
      brief period of time, the authors suggest that further investigation of EMDR for
      depressive disorders is warranted.

PMID- 20046411
TI  - Stenting versus bypass surgery for the treatment of left main coronary artery
      disease.
AB  - Based on data comparing coronary-artery bypass grafting (CABG) with medical
      therapy, the current guidelines recommend CABG as the treatment of choice for
      patients with left main coronary artery (LMCA) disease. Percutaneous coronary
      intervention (PCI) can be selectively performed in patients who are candidates
      for revascularization but who are ineligible for CABG. Current evidence indicates
      that stenting results in mortality and morbidity rates compared favorably with
      those seen after CABG. Data from several extensive registries and a large
      clinical trial may have prompted many interventional cardiologists to choose PCI
      with stenting as an alternative treatment option for such patients. In addition,
      these data may inform future guidelines and support the need for well-designed,
      adequately powered, prospective, randomized trials comparing the two
      revascularization strategies.

PMID- 20046413
TI  - Are there gaps between medical students and professors in the perception of
      students' professionalism level?--Secondary publication.
AB  - PURPOSE: The implementation of medical professionalism in education and
      evaluation is a recent trend in medical education. Although many studies on the
      subject have been carried out, they have generally been not focused specifically
      on the level of medical student professionalism, and the perception gaps between
      medical students and professors on this topic remain unresolved. This study
      attempts to determine whether such gaps exist. MATERIALS AND METHODS: Two hundred
      fifty fourth-year medical students and 53 professors who were randomly selected
      from 41 medical schools were asked to complete a survey on the level of the
      professionalism of medical students. Using 31 core professionalism elements that
      are required for Korean medical students, students self-assessed their level of
      professionalism, and professors evaluated the professionalism level of medical
      students who were about to graduate. RESULTS: Of the 31 core elements,
      significant perception gaps were found in 28 elements. The three domains into
      which the 31 core elements were divided - professional knowledge, professional
      skills, and professional attitude - all contained perception gaps, and
      professors' ratings generally were higher than those of the students, a
      noteworthy observation. CONCLUSIONS: Medical professors need to encourage their
      students to elevate their professionalism. Furthermore, what the faculty think
      that they have taught regarding professionalism may not be fully assimilated by
      students. Therefore, further research is essential to determine the cause of such
      perceptional differences.

PMID- 20046412
TI  - Update on recent advances in the management of aspirin exacerbated respiratory
      disease.
AB  - Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)
      exacerbated respiratory disease (AERD). It is a clinical syndrome associated with
      chronic severe inflammation in the upper and lower airways resulting in chronic
      rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops
      secondary to abnormalities in inflammatory mediators and arachidonic acid
      biosynthesis expression. Upper and lower airway eosinophil infiltration is a key
      feature of AERD; however, the exact mechanisms of such chronic eosinophilic
      inflammation are not fully understood. Cysteinyl leukotriene over-production may
      be a key factor in the induction of eosinophilic activation. Genetic studies have
      suggested a role for variability of genes in disease susceptibility and response
      to medication. Potential genetic biomarkers contributing to the AERD phenotype
      include HLA-DPB1*301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 
      1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was
      composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T >
      C. Management of AERD is an important issue. Aspirin ingestion may result in
      significant morbidity and mortality, and patients must be advised regarding
      aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene
      pathways have an established role in long-term AERD management and
      rhinosinusitis. Aspirin desensitization may be required for the relief of upper
      and lower airway symptoms in AERD patients. Future research should focus on
      identification of biomarkers for a comprehensive diagnostic approach.

PMID- 20046414
TI  - Increased inflammation, reduced plasma phospholipid eicosapentaenoic acid and
      reduced antioxidant potential of treated hypertensive patients with metabolic
      syndrome.
AB  - PURPOSE: In the present study, we tested whether the presence of metabolic
      syndrome (MetS) would worsen the features of inflammation, plasma omega 3 fatty
      acid levels and antioxidant potential in treated hypertensive patients. MATERIALS
      AND METHODS: TWO GROUPS WERE CLASSIFIED BY THE COMPONENTS OF METS: a reference
      group of treated hypertensive subjects: hypertension (HTN) group (n = 39) and
      with more than two additional MetS components: HTN with Mets group (n = 40). We
      further compared the parameters between HTN group and HTN with MetS group.
      RESULTS: The results showed that age (p < 0.001) and body mass index (BMI) (p <
      0.001) were significantly different between HTN group and HTN with MetS group.
      Age- and BMI-adjusted total radical trapping antioxidant potential (TRAP) (p <
      0.01) was significantly lower, whereas age- and BMI-adjusted CD (p < 0.05) and
      interleukin (IL) 6 (p < 0.05) were significantly higher in HTN with MetS group
      than in HTN group. Moreover, HTN with MetS group had significantly lower levels
      of age- and BMI-adjusted plasma phospholipid eicosapentaenoic acid (EPA) than HTN
      group (p < 0.05). On the other hand, the levels of age- and BMI-adjusted
      intracellular cell adhesion molecule-1 (ICAM-1), adiponectin and high molecular
      weight (HMW)-adiponectin were not significantly different between the groups.
      CONCLUSION: In conclusion, our results showed increased inflammatory marker,
      reduced antioxidant potential and EPA levels in treated hypertensive patients in
      the presence of MetS, suggesting the importance of changes of therapeutic
      lifestyle to modify the features of MetS.

PMID- 20046415
TI  - Outbreaks of imipenem resistant Acinetobacter baumannii producing OXA-23 beta
      lactamase in a tertiary care hospital in Korea.
AB  - PURPOSE: Since November 2006, imipenem-resistant Acinetobacter baumannii isolates
      have increased in Kyung Hee University Hospital in Seoul, Korea. The purpose of
      this study was to determine the genetic basis and molecular epidemiology of
      outbreak isolates. MATERIALS AND METHODS: Forty-nine non-repetitive isolates of
      the 734 IRAB strains were investigated in order to determine their
      characteristics. The modified Hodge and the ethylenediaminetetraacetic acid
      (EDTA)-disk synergy test were performed for the screening of carbapenemase and
      metallo-beta-lactamase production. Multiplex polymerase chain reaction (PCR)
      assays were performed for the detection of genes encoding for OXA-23-like, OXA-24
      like, OXA-58-like and OXA-51-like carbapenemase. Pulsed-field gel electrophoresis
      (PFGE) was performed for strain identification. RESULTS: All isolates showed 100%
      resistance to ciprofloxacin and gentamicin, 97.9% resistance to cefepime,
      piperacillin/tazobactam, aztreonam, ceftazidime and piperacillin, 93.9%
      resistance to tobramycin and 57.1% resistance to amikacin. All of the 49 isolates
      (100%) showed positive results in the modified Hodge test and negative results in
      the EDTA-disk synergy test. They all (100%) possessed the encoding gene for an
      intrinsic OXA-51-like carbapenemase and an acquired OXA-23-like carbapenemase in
      the multiplex PCR assay. PFGE patterns revealed that all isolates were clonally
      related from A1 to A14. CONCLUSION: It is concluded that all of the 49 IRAB
      isolates acquired resistance to imipenem by producing OXA-23 carbapenemase and
      they might have originated from a common source.

PMID- 20046416
TI  - Hearing threshold of Korean adolescents associated with the use of personal music
      players.
AB  - PURPOSE: Hearing loss can lead to a number of disabilities and can reduce quality
      of life. Noise-induced hearing losses have become more common among adolescents
      due to increased exposure to personal music players. We, therefore, investigated
      the use of personal music player among Korean adolescents and the relationship
      between hearing threshold and usage pattern of portable music players. MATERIALS
      AND METHODS: A total of 490 adolescents were interviewed personally regarding
      their use of portable music players, including the time and type of player and
      the type of headphone used. Pure tone audiometry was performed in each subject.
      RESULTS: Of the 490 subjects, 462 (94.3%) used personal music players and most of
      them have used the personal music player for 1-3 hours per day during 1-3 years.
      The most common type of portable music player was the MP3 player, and the most
      common type of headphone was the earphone (insert type). Significant elevations
      of hearing threshold were observed in males, in adolescents who had used portable
      music players for over 5 years, for those over 15 years in cumulative period and
      in those who had used earphones. CONCLUSION: Portable music players can have a
      deleterious effect on hearing threshold in adolescents. To preserve hearing,
      adolescents should avoid using portable music players for long periods of time
      and should avoid using earphones.

PMID- 20046417
TI  - Cheiro-oral syndrome: a clinical analysis and review of literature.
AB  - PURPOSE: After a century, cheiro-oral syndrome (COS) was harangued and emphasized
      for its localizing value and benign course in recent two decades. However, an
      expanding body of case series challenged when COS may arise from an involvement
      of ascending sensory pathways between cortex and pons and terminate into poor
      outcome occasionally. MATERIALS AND METHODS: To analyze the location, underlying
      etiologies and prognosis in 76 patients presented with COS collected between 1989
      and 2007. RESULTS: Four types of COS were categorized, namely unilateral (71.1%),
      typically bilateral (14.5%), atypically bilateral (7.9%) and crossed COS (6.5%).
      The most common site of COS occurrence was at pons (27.6%), following by thalamus
      (21.1%) and cortex (15.8%). Stroke with small infarctions or hemorrhage was the
      leading cause. Paroxysmal paresthesia was predicted for cortical involvement and
      bilateral paresthesia for pontine involvement, whereas crossed paresthesia for
      medullary involvement. However, the majority of lesions cannot be localized by
      clinical symptoms alone, and were demonstrated only by neuroimaging.
      Deterioration was ensued in 12% of patients, whose lesions were large cortical
      infarction, medullary infarction, and bilateral subdural hemorrhage. CONCLUSION:
      COS arises from varied sites between medulla and cortex, and is usually caused by
      small stroke lesion. Neurological deterioration occurs in 12% of patients and
      relates to large vessel occlusion, medullary involvement or cortical stroke.
      Since the location and deterioration of COS cannot be predicted by clinical
      symptoms alone, COS should be considered an emergent condition for aggressive
      investigation until fatal cause is substantially excluded.

PMID- 20046418
TI  - Withdrawal of immunosuppression in pediatric liver transplant recipients in
      Korea.
AB  - PURPOSE: We identified pediatric liver transplant recipients with successful
      withdrawal of immunosuppression who developed tolerance in Korea. MATERIALS AND
      METHODS: Among 105 pediatric patients who received liver transplantation and were
      treated with tacrolimus-based immunosuppressive regimens, we selected five (4.8%)
      patients who had very low tacrolimus trough levels. Four of them were
      noncompliant with their medication and one was weaned off of immunosuppression
      due to life threatening posttransplant lymphoproliferative disorder. We reviewed
      the medical records with regard to the relationship of the donor-recipients,
      patient characteristics and prognosis, including liver histology, and compared
      our data with previous reports. RESULTS: Four patients received the liver
      transplantation from a parent donor and one patient from a cadaver donor. A trial
      of withdrawal of the immunosuppressant was started a median of 45 months after
      transplantation (range, 14 months to 60 months), and the period of follow up
      after weaning from the immunosuppressant was a median of 32 months (range, 14
      months to 82 months). None of the five patients had rejection episodes after
      withdrawal of the immunosuppression; they maintained normal graft function for
      longer than 3 years (median, 38 months; range, 4 to 53 months). The histological
      findings of two grafts 64 and 32 months after weaning-off of the medication
      showed no evidence of chronic rejection. CONCLUSION: The favorable markers for
      successful withdrawal of immunosuppression were 1) long-term (> 3 years) stable
      graft function, 2) no rejection for longer than 1 year after withdrawal of
      immunosuppression, 3) non-immune mediated liver diseases, and 4) pediatric
      patients.

PMID- 20046419
TI  - Preoperative radiologic and postoperative pathologic risk factors for early intra
      hepatic recurrence in hepatocellular carcinoma patients who underwent curative
      resection.
AB  - PURPOSE: The risk of hepatocellular carcinoma (HCC) recurrence must be considered
      ahead of surgery. This study was undertaken to identify pre-operative risk
      factors for early intrahepatic recurrence of HCC after curative resection in a
      large-scale. MATERIALS AND METHODS: We retrospectively reviewed the preoperative
      three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who
      underwent curative resection; tumor size, number, gross shape, capsule integrity,
      distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein
      level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were
      assessed. Surgical pathology was reviewed; tumor differentiation, capsule,
      necrosis, and micro-vessel invasion were recorded. RESULTS: HCC recurred in 61
      patients within six months (early recurrence group), but not in 179 patients
      (control group). In univariate analysis, large tumor size (p = 0.018), shape (p =
      0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA
      II (p = 0.008) were significant preoperative risk factors. Among the pathologic
      features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033),
      microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed
      statistical significance. In multivariate analysis, only the histopathologic
      parameters of microvascular invasion and poor differentiation achieved
      statistical significance. CONCLUSION: Preoperative CT and laboratory parameters
      showed limited value, while the presence of microscopic vascular tumor invasion
      and poorly differentiated HCC correlated with higher risk of early recurrence
      after curative resection.

PMID- 20046420
TI  - Compliance and effective management of the hand-foot syndrome in colon cancer
      patients receiving capecitabine as adjuvant chemotherapy.
AB  - PURPOSE: Physicians and oncology nurses must continue to update their knowledge
      on treatment and treatment-related side effects, while searching for effective
      methods to prevent or manage side effects. The objective of our study was to
      describe the incidence and response to treatment of the hand-foot syndrome (HFS)
      and the compliance with treatment of patients with stage IIB, IIIA, IIIB, and
      IIIC colon cancer that were treated with capecitabine alone as adjuvant therapy.
      MATERIALS AND METHODS: Between September 2005 and September 2006, 84 patients
      fulfilled the inclusion criteria and were included in this retrospective analysis
      of prospectively collected data. RESULTS: The treatment compliance rate was 90.5%
      (76 out of the 84 patients). The HFS developed in 65 patients (77.4%). Thirty
      three patients (50.7%) had grade 1 HFS, 22 patients (33.8%) had grade 2 HFS and
      10 patients (15.5%) had grade 3 HFS, as their most severe episode. For Grade 1
      patients, the dose was maintained, and skin barrier cream and moist exposed burn
      ointment (MEBO) were applied. For Grade 2 patients, either the dose was
      maintained or 25% of the dose was reduced; MEBO and supportive care were
      provided. For Grade 3 patients, one cycle of chemotherapy was interrupted
      followed by dose adjustment; MEBO and supportive care were provided. CONCLUSION:
      HFS is manageable if both patients and oncology care teams are educated about HFS
      associated with capecitabine. The HFS is treated by patient education, preventive
      management, ointment application, conservative management, dose reduction, and
      interruption of chemotherapy administration.

PMID- 20046421
TI  - En bloc resection for right colon cancer directly invading duodenum or pancreatic
      head.
AB  - PURPOSE: We undertook this study to analyze clinical features and surgical
      outcome of en bloc resections of the right side colon cancer directly invading
      duodenum and/or pancreatic head. MATERIALS AND METHODS: The records of all
      patients who underwent en bloc resection of duodenum and/or pancreas for right
      colon cancers were analyzed retrospectively. From September 1994 to September
      2006, 1,016 patients underwent curative right hemicolectomy. Nine patients (0.9%)
      had en bloc resection of a right side colon cancer with duodenum or pancreatic
      head invasion. RESULTS: The median operative time was 320 minutes (range, 200
      420) and the median blood loss was 700 mL (range, 100-2,000). The mean size of
      tumor was 6.6 cm (range, 3.2-10.7). The mean preoperative carcinoembryonic
      antigen (CEA) was 10.6 ng/mL (range, 0.2-50.8). There was no 30 day perioperative
      mortality. The median disease-free survival was 23.5 months [95% confidence
      interval (CI) 5.2-41.8] and the median overall survival was 28.1 months (95% CI
      9.7-46.5). CONCLUSION: In patients with locally advanced right side colon cancer
      that directly invades the duodenum or pancreas can be safely resected with
      curative potential with minimum morbidity and mortality. Long term disease free
      survival can occur in a significant number of patients undergoing curative en
      bloc resection in this particular subset of patients.

PMID- 20046422
TI  - A long-term treatment outcome of abdominal sacrocolpopexy.
AB  - PURPOSE: The aim of this study was to evaluate the long-term treatment outcome
      and major complication rates of abdominal sacrocolpopexy (ASC). MATERIALS AND
      METHODS: This retrospective study included 57 Korean women who underwent ASC with
      mesh for symptomatic uterine or vault prolapse and attended follow-up visits for
      at least 5 years. Forty-seven women with urodynamic stress incontinence
      concomitantly received a modified Burch colposuspension. The long-term anatomical
      and functional outcomes and complication rates were assessed. RESULTS: The median
      follow-up was 66 months (range 60-108). Overall anatomical success rates (no
      recurrence of any prolapse >or= stage II according to the pelvic organ prolapse
      quantification system) were 86.0%. Urinary urgency and voiding dysfunction were
      significantly improved after surgery, however, recurrent stress urinary
      incontinence developed in 44.7% (21/47) of cases and half of them developed
      within 1-3 months post-op. Bowel function (constipation and fecal incontinence)
      and sexual function (sexual activity and dyspareunia) did not significantly
      change after surgery. Major complication requiring reoperation or intensive care
      developed in 12 (21.0%) cases. CONCLUSIONS: ASC provides durable pelvic support,
      however, it may be ineffective for alleviating pelvic floor dysfunction except
      for urinary urgency and voiding dysfunction, and it contains major complication
      risk that cannot be overlooked.

PMID- 20046423
TI  - Analysis of soft tissue changes after genioplasty in skeletal class III
      dentofacial deformity.
AB  - PURPOSE: The purpose of this study was to measure the anteroinferior changes and
      the degree of vertical changes to facilitate the prediction of treatment outcome
      in patients undergoing genioplasty only, genioplasty with bilateral sagittal
      split ramus osteotomy (BSSRO), genioplasty, or BSSRO and Lefort I osteotomy.
      MATERIALS AND METHODS: Serial cephalometry was performed on 25 patients at 1-year
      follow-up after genioplasty, to assess skeletal changes and relapse. Surgery was
      performed using conventional techniques. RESULTS: The mean ratio was 0.9:1 of
      soft tissue to skeletal movement at pogonion, but the average difference between
      hard and soft tissue was large; thus, the prediction of anteroposterior soft
      tissue changes was quite inaccurate. CONCLUSION: We observed a good correlation
      between the amount of hard versus soft tissue change with surgery in the
      horizontal direction, but a poor correlation in the vertical plane.

PMID- 20046424
TI  - Cyclooxygenase-2 expression is related to the epithelial-to-mesenchymal
      transition in human colon cancers.
AB  - PURPOSE: Down-regulation of E-cadherin is a hallmark of the epithelial-to
      mesenchymal transition (EMT). EMT progression in cancer cells is associated with
      the loss of certain epithelial markers and the acquisition of a mesenchymal
      phenotype, as well as migratory activities. Cyclooxygenase-2 (COX-2) expression
      is associated with tumor invasion and metastasis in colon cancer. This study
      investigated the relationship between E-cadherin and COX-2 in colon cancer cells
      and human colon tumors. MATERIALS AND METHODS: Colon cancer cell lines and
      immunohistochemistry were used. RESULTS: E-cadherin expression was inversely
      related to the expressions of COX-2 and Snail in colon cancer cells. Ectopic
      expression of COX-2 or Snail reduced E-cadherin and induced a scattered,
      flattened phenotype with few intercellular contacts in colon cancer cells.
      Treatment of cancer cells with phorbol 12-myristate 13-acetate increased the
      expressions of COX-2 and Snail, decreased 15-hydroxyprostaglandin dehydrogenase
      expression, and increased the cells' motility. In addition, exposure to
      prostaglandin E(2) increased Snail expression and cell motility, and decreased E
      cadherin expression. Membranous E-cadherin expression was lower in adenomas and
      cancers than in the adjacent, non-neoplastic epithelium. In contrast, the
      expressions of Snail and COX-2 were higher in cancers than in normal tissues and
      adenomas. The expressions of COX-2 and Snail increased in areas with abnormal E
      cadherin expression. Moreover, COX-2 expression was related to higher tumor
      stages and was significantly higher in nodal metastatic lesions than primary
      cancers. CONCLUSION: This study suggests that COX-2 may have a role in tumor
      metastasis via EMT.

PMID- 20046425
TI  - Effects of polycaprolactone-tricalcium phosphate, recombinant human bone
      morphogenetic protein-2 and dog mesenchymal stem cells on bone formation: pilot
      study in dogs.
AB  - PURPOSE: The aim of this study was to evaluate the survival, proliferation, and
      bone formation of dog mesenchymal stem cells (dMSCs) in the graft material by
      using Polycaprolactone-tricalcium phosphate (PCL-TCP), auto-fibrin glue (AFG),
      recombinant human bone morphogenetic protein-2 (rhBMP-2), and dMSCs after a
      transplantation to the scapula of adult beagle dogs. MATERIALS AND METHODS: The
      subjects were two beagle dogs. Total dose of rhBMP-2 on each block was 10 microg
      with 50 microg/mg concentration. The cortical bone of the scapula of the dog was
      removed which was the same size of PCL-TCP block (Osteopore International Pte,
      Singapore; 5.0x5.0x8.0 mm in size), and the following graft material then was
      fixed with orthodontic mini-implant, Dual-top (Titanium alloy, Jeil Co. Seoul,
      Korea). Four experimental groups were prepared for this study, Group 1: PCL-TCP +
      aFG; Group 2: PCL-TCP + aFG + dMSCs; Group 3: PCL-TCP + aFG + dMSCs + rhBMP-2;
      Group 4: PCL-TCP + aFG + dMSCs + rhBMP-2 + PCL membrane. The survival or
      proliferation of dMSCs cells was identified with an extracted tissue through a
      fluorescence microscope, H-E staining and Von-Kossa staining in two weeks and
      four weeks after the transplantation. RESULTS: The survival and proliferation of
      dMSCs were identified through a fluorescence microscope from both Group 1 and
      Group 2 in two weeks and four weeks after the transplantation. Histological
      observation also found that the injected cells were proliferating well in the G2,
      G3, and G4 scaffolds. CONCLUSION: This study concluded that bone ingrowth
      occurred in PCL-TCP scaffold which was transplanted with rhBMP-2, and MSCs did
      not affect bone growth. More sufficient healing time would be needed to recognize
      effects of dMSCs on bone formation.

PMID- 20046426
TI  - The protective effect of sodium hyaluronate on the cartilage of rabbit
      osteoarthritis by inhibiting peroxisome proliferator-activated receptor-gamma
      messenger RNA expression.
AB  - PURPOSE: The purpose of this study was to study the protective effect and
      influence of sodium hyaluronate (Na-HA) on mRNA expression of peroxisome
      proliferators-activated receptor gamma (PPAR-gamma) in cartilage of rabbit
      osteoarthritis (OA) model. MATERIALS AND METHODS: Forty eight white rabbits were
      randomly divided into A, B, and C groups. Group A was normal control group, B and
      C groups underwent unilateral anterior cruciate ligament transection (ACLT). The
      rabbits in group B were injected normal saline after ACLT; and Group C received
      intra-articular 1% sodium hyaluronate (HA) injection 5 weeks after surgery, 0.3
      mL once a week. At 11th week after surgery, all the rabbits were sacrificed. The
      cartilage changes on the medial femoral condyles were graded separately.
      Cartilage sections were stained with safranin-O and HE, and messenger RNA (mRNA)
      expression of PPAR-gamma was detected by using real time polymerase chain
      reaction (Real Time-PCR). RESULTS: Cartilage degeneration in group B was
      significantly more severe than in A and C injection group. The grey value of
      Safranin-O of B group was higher than A and C groups. Expression of PPAR-gamma
      mRNA in group B was higher than group A and C. CONCLUSION: This study shows that
      Na-HA has a protective effect on articular cartilage degeneration, and the
      inhibitory effect on the PPAR-gamma mRNA expression may be one of therapeutic
      mechanism of Na-HA.

PMID- 20046427
TI  - Diagnostic value of 3D fast low-angle shot dynamic MRI of breast papillomas.
AB  - PURPOSE: To evaluate the value of breast MRI in analysis of papillomas of the
      breast. MATERIALS AND METHODS: From 1996 to 2004, 94 patients underwent surgery
      due to papillomas of the breast. Among them, 21 patients underwent 3D fast low
      angle shot (FLASH) dynamic breast MRI. Eight masses were palpable and 11 of 21
      patients had nipple discharge. Two radiologists indifferently analyzed the
      location, size of the lesions and shape, margin of the masses, multiplicity and
      ductal relation. The MRI findings were categorized according to breast imaging
      reporting and data system (BI-RADS) lexicon. The amount and pattern of
      enhancement and associated findings were also evaluated according to BI-RADS. We
      then compared the MRI findings with galactography, mammography and breast
      ultrasonography (US) and examined histopathologic correlation. RESULTS: On breast
      MRI, the lesion size was 0.4-1.59 cm, and 18 patients showed subareolar location.
      On 4.25 cm (mean 1.54) dynamic enhanced images, imaging findings showed mass (n =
      10), intracystic mass (n = 3), focus (n = 5), ductal enhancement (n = 2), and
      segmental enhancement (n = 1). In cases of the masses, the shapes of the masses
      were round (n = 4), lobulated (n = 3), and irregular (n = 6), and margins were
      circumscribed (n = 6), microlobulated (n = 5), and indistinct (n = 2). The
      enhancement patterns were homogeneous enhancement (n = 7), heterogeneous (n = 3)
      or rim enhancement (n = 3). CONCLUSION: The contrast enhanced dynamic breast MRI
      was highly sensitive for diagnosis of breast papillomas. MRI could play a key
      role in the pre-operative work-up for multiple papillomas and papillomatosis.

PMID- 20046428
TI  - A case of dysplastic nevus of the external auditory canal presenting with
      conductive hearing loss.
AB  - A nevus which is a benign melanocytic neoplasm rarely occurs within the external
      auditory canal (EAC). A dysplastic nevus presents atypical features both
      clinically and histologically, and is important as a potential precursor for
      melanoma. We present a case of a 33-year-old female patient with a dysplastic
      nevus in her EAC. Physical examination revealed a protruding mass arising from
      the posterior wall of the left cartilaginous EAC. The mass showed clinically
      characteristic findings of a melanocytic nevus. The patient underwent excisional
      biopsy via a transcanal approach under local anesthesia. Histopathological
      examination revealed an intradermal nevus with atypical melanocytes without
      pleomorphism. There was no evidence of recurrence two years after surgical
      excision.

PMID- 20046429
TI  - Malignant myoepithelioma of the palate: a case report with review of the
      clinicopathological characteristics.
AB  - A malignant myoepithelioma is one of the rarest salivary gland neoplasms which
      may either arise de novo or develop within a preexisting pleomorphic adenoma or
      benign myoepithelioma. The parotid gland is the most common primary site and the
      palate the most common intra-oral site of occurrence. Herein is present a case of
      a malignant myoepithelioma arising in the hard palate of a 79-year-old woman. The
      lesion had been examined by biopsy at another hospital, and diagnosed as a poorly
      differentiated squamous cell carcinoma. The patient underwent a wide local tumor
      resection. Examination of the resection specimen showed the characteristic
      histopathological and immunohistochemical features of a malignant myoepithelioma.
      Five months after the operation, the patient was well without evidence of
      recurrence or metastasis.

PMID- 20046430
TI  - Coronary-subclavian steal syndrome presenting with ventricular tachycardia.
AB  - Coronary-subclavian steal through the left internal mammary graft is a rare cause
      of myocardial ischemia in patients who have had a coronary bypass surgery. We
      report a 70-year-old man who presented with sustained monomorphic ventricular
      tachycardia 5 years after the surgical creation of a left internal mammary to the
      left anterior descending artery. Cardiac catheterization illustrated that the
      left subclavian artery was occluded proximally and that the distal course was
      visualized by retrograde filling through the left internal mammary graft.
      Clinical ventricular tachycardia was reproducibly induced with a single
      ventricular extrastimulus, and antitachycardia pacing terminated the tachycardia.
      Restoration of blood flow by way of a Dacron graft placed between the descending
      aorta and the subclavian artery resulted in the total relief of symptoms.
      Ventricular tachycardia could not be induced during the control
      electrophysiologic study after surgical revascularization.

PMID- 20046431
TI  - A Giant pulmonary hydatid cyst treated without lobectomy.
AB  - A 20 year-old woman was admitted to our clinic complaining of dyspnea, cough,
      chest pain and pleural effusion. The diagnosis of pulmonary hydatid cyst was made
      on the basis of parasitology laboratory findings, computed tomographic results
      and chest radiographic findings. A giant pulmonary hydatid cyst (33x14x12 cm) was
      located in the left lower lobe, which involved more than 90% of the lobe. The
      patient was treated surgically using cystotomy and capitonnage. This is a case of
      a giant pulmonary hydatid cyst published in the literature, which was surgically
      treated without a lobectomy, by preserving the lung parenchyma.

PMID- 20046432
TI  - Case of small bowel perforation due to enteropathy-type T-cell lymphoma.
AB  - Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis.
      According to the World Health Organization (WHO) classification, it is a subtype
      of the peripheral T-cell lymphomas. This disease is associated with gluten
      sensitive enteropathy, has a high risk of intestinal perforation and obstruction,
      and is refractory to chemotherapeutic treatment. We report the case of a 73-year
      old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small
      intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and
      CD56, on immunohistochemical staining after resection of the perforated terminal
      ileum.

PMID- 20046433
TI  - Primary effusion lymphoma: an untrivial differential diagnosis for ascites.
AB  - A primary effusion lymphoma is a rare type of non-Hodgkin's lymphoma where serous
      cavities are involved. That-cause peritoneal, pleural and pericardial effusions
      without any lymphadenopathy. They affect immunosuppressive patients with human
      herpes virus-8 being the suspected etiological agent. The prognosis is usually
      poor despite treatment. Herein, the case of an immunocompetent patient with
      ascites and pleural effusion diagnosed as primary effusion lymphoma is presented
      and discuss the case in the light of the current literature.

PMID- 20046435
TI  - Assessing immunization programs.

PMID- 20046436
TI  - A call to arms (and legs): Implement the National Immunization Strategy.

PMID- 20046434
TI  - Successful treatment of enterocutaneous fistula in a hemodialysis patient with
      somatostatin.
AB  - Although cysticercosis is the most common parasitic disease affecting the central
      nervous system, spinal cysticercosis is rare. A rare form of spinal cysticercosis
      involving the whole spinal canal is presented. A 45-year-old Korean male had a
      history of intracranial cysticercosis and showed progressive paraparesis. Spinal
      magnetic resonance scan showed multiple cysts compressing the spinal cord from C1
      to L1. Three different levels (C1-2, T1-3, and T11-L1) required operation.
      Histopathological examination confirmed cysticercosis. The patient improved
      markedly after surgery.

PMID- 20046437
TI  - Reaching the target for global polio eradication - almost there!

PMID- 20046438
TI  - Battle over Children's rights at the United Nations Special Session on Children.

PMID- 20046439
TI  - Clinician's Corner.

PMID- 20046440
TI  - Clinician's Corner.

PMID- 20046441
TI  - Meningococcal and pneumococcal disease.

PMID- 20046442
TI  - Immunization and children at risk for autism.
AB  - Possible connections between immunization and developmental disorders, most
      notably autistic disorders, have been the subject of a great deal of debate and
      have caused much concern for parents who want to make the safest choices for
      their children. Anxiety has risen steadily since the mid-1990s, when a medical
      investigative team led by A Wakefield postulated that the measles-mumps-rubella
      (MMR) vaccine may be a causative factor in the development of autism spectrum
      disorder. Since this initial publication, immunization remains controversial for
      some parents and the uptake of the MMR vaccine has fallen in some countries,
      despite much discussion regarding the safety of MMR, a lack of evidence for an
      association between MMR and autism, and the risks of insufficient protection
      against wild measles virus infection. The Canadian uptake of MMR in 1998 was 95%,
      but data do not exist to document any change in Canada since that time. Many
      clinicians are concerned that the uptake in younger siblings of children with
      autism is considerably lower.Further anxiety for parents has been caused by the
      suggested association between developmental disorders and mercury toxicity due to
      thimerosal, which is used as a preservative in some vaccines. Many Canadian
      parents, while continuing to seek chelation therapy in response to this
      suggestion, are not aware that, in Canada, thimerosal has never been added to
      MMR, and has not been present in diphtheria-pertussis-tetanus-poliomyelitis or
      pentavalent vaccines since 1992. It is found in only Hepatitis B vaccine in some
      provinces.The present article is intended to be a guide for physicians as they
      counsel parents.

PMID- 20046443
TI  - Childhood drowning in Manitoba: A 10-year review of provincial Paediatric Death
      Review Committee data.
AB  - BACKGROUND: Drowning is the second leading cause of unintentional injury death
      for Canadian children up to 19 years of age. Specific regional drowning
      prevention strategies require a detailed understanding of patterns of injury,
      including risk factors. Paediatric death review committees have the opportunity
      to identify these risk factors, and to identify and advocate prevention
      strategies. OBJECTIVES: The purpose of the present study was to analyze Manitoba
      Paediatric Death Review Committee (PDRC) drowning data to identify drowning risk
      factors and potential prevention strategies. METHODS: A 10-year (1988-1997)
      review of the College of Physicians and Surgeons of Manitoba PDRC database was
      performed. Drowning deaths were summarized in terms of demographic variables and
      lack of supervision at the time of the drowning events. RESULTS: Seventy-three
      drowning deaths were reviewed by the PDRC during the study period. These children
      ranged from 29 days to 14 years of age. They included 50 boys and 30 First
      Nations children. The highest mortality rates were found in First Nations
      children (12.4/100,000 First Nations children compared with 1.9/100,000 non-First
      Nations children), boys (3.9/100,000 boys compared with 1.9/100,000 girls) and
      toddlers aged one to four years (5.9/100,000 children). CONCLUSIONS: Priority
      populations for drowning prevention in Manitoba include First Nations children,
      boys and toddlers. Death review committees can contribute to childhood injury
      prevention by reviewing injury deaths, analyzing and reporting injury mortality
      data, and identifying and advocating prevention strategies.

PMID- 20046445
TI  - Pneumococcal vaccine.

PMID- 20046444
TI  - Assuring vaccine safety: A celebration of 10 years of progress with the IMPACT
      project.

PMID- 20046446
TI  - Attention deficit hyperactivity disorder.

PMID- 20046448
TI  - A risk of northern climate!

PMID- 20046447
TI  - Attention deficit hyperactivity disorder - Medical malady or societal madness?

PMID- 20046449
TI  - Life in the last lane.

PMID- 20046450
TI  - Is methylphenidate effective in reducing symptoms of attention deficit
      hyperactivity disorder in school-aged children?

PMID- 20046451
TI  - The use of stimulant medication in the treatment of attention deficit
      hyperactivity disorder.

PMID- 20046452
TI  - Medical treatment for attention deficit hyperactivity disorder.

PMID- 20046454
TI  - Faculty responsible for the accreditation process of medical education in Korea
      should have their workloads reduced.

PMID- 20046453
TI  - The use of alternative therapies in treating children with attention deficit
      hyperactivity disorder.

PMID- 20046455
TI  - Experiences of accreditation of medical education in taiwan.
AB  - THIS REVIEW AIMS TO INTRODUCE THE TAIWANESE MEDICAL ACCREDITATION SYSTEM: its
      history, role and future goals. In 1999, the Ministry of Education, Taiwanese
      Government commissioned the non-profit National Health Research Institutes (NHRI)
      to develop a new medical accreditation system. According to that policy, the
      Taiwan Medical Accreditation Council (TMAC) was established in the same year. The
      council serves a similar function to that of the Liaison Committee on Medical
      Education (LCME) of the United States and the Australian Medical Council (AMC).
      The accreditation process consists of a self-assessment plus a four-day site
      visit by a team of eight medical educators that are headed by one of the council
      members of the TMAC. The first cycle of initial visits was completed from 2001 to
      2004. Subsequent follow-up visits were arranged according to the results of the
      survey with smaller-sized teams and shorter periods. There is evidence to suggest
      that the majority (seven of eleven) of the medical schools in Taiwan have made
      good progress. TMAC's next step will be to monitor the progress and raise the
      standard of medical education in individual schools with a homogenous, superior
      standard of medical education.

PMID- 20046456
TI  - Patient simulation: a literary synthesis of assessment tools in anesthesiology.
AB  - High-fidelity patient simulation (HFPS) has been hypothesized as a modality for
      assessing competency of knowledge and skill in patient simulation, but uniform
      methods for HFPS performance assessment (PA) have not yet been completely
      achieved. Anesthesiology as a field founded the HFPS discipline and also leads in
      its PA. This project reviews the types, quality, and designated purpose of HFPS
      PA tools in anesthesiology. We used the systematic review method and
      systematically reviewed anesthesiology literature referenced in PubMed to assess
      the quality and reliability of available PA tools in HFPS. Of 412 articles
      identified, 50 met our inclusion criteria. Seventy seven percent of studies have
      been published since 2000; more recent studies demonstrated higher quality.
      Investigators reported a variety of test construction and validation methods. The
      most commonly reported test construction methods included "modified Delphi
      Techniques" for item selection, reliability measurement using inter-rater
      agreement, and intra-class correlations between test items or subtests. Modern
      test theory, in particular generalizability theory, was used in nine (18%) of
      studies. Test score validity has been addressed in multiple investigations and
      shown a significant improvement in reporting accuracy. However the assessment of
      predicative has been low across the majority of studies. Usability and
      practicality of testing occasions and tools was only anecdotally reported. To
      more completely comply with the gold standards for PA design, both shared
      experience of experts and recognition of test construction standards, including
      reliability and validity measurements, instrument piloting, rater training, and
      explicit identification of the purpose and proposed use of the assessment tool,
      are required.

PMID- 20046457
TI  - Introduction to an open source internet-based testing program for medical student
      examinations.
AB  - The author developed a freely available open source internet-based testing
      program for medical examination. PHP and Java script were used as the programming
      language and postgreSQL as the database management system on an Apache web server
      and Linux operating system. The system approach was that a super user inputs the
      items, each school administrator inputs the examinees' information, and examinees
      access the system. The examinee's score is displayed immediately after
      examination with item analysis. The set-up of the system beginning with
      installation is described. This may help medical professors to easily adopt an
      internet-based testing system for medical education.

PMID- 20046458
TI  - Evaluation of a team-based learning tutor training workshop on research and
      publication ethics by faculty and staff participants.
AB  - A team-based Learning (TBL) tutor training workshop on research and publication
      ethics was offered to 8 faculty members and 3 staff at Hallym University in 2009.
      To investigate the effect of the workshop and any attitude changes, a
      questionnaire survey was performed after the 8-hr course. Questions in four
      categories-general course content, change in attitudes toward research and
      publication ethics, the TBL format, and an open-ended question about the course-
      were included. Participants responded positively to all items on general course
      content. There was a positive change in attitude on research and publication
      ethics. Participants also responded positively to six items on team-based
      learning. The overall positive response to the workshop on research and
      publication ethics suggested the effectiveness of this kind of TBL tutor training
      course for university faculty and staff.

PMID- 20046459
TI  - Animation-based lectures in renal physiology: transcendence into metacognition.

PMID- 20046460
TI  - From soap and water, to waterless agents: Update on hand hygiene in healthcare
      settings.

PMID- 20046461
TI  - Searching for the evidence: The process involved.

PMID- 20046462
TI  - Paediatric bladder augmentation and substitution: From diversions to tissue
      engineering.
AB  - OBJECTIVES: To review the evolution of urinary diversion, bladder augmentation
      and bladder replacement in the paediatric population over the past century and to
      outline the possible direction of future management. DATA SOURCES: Original and
      review articles obtained from a PubMed search of English language publications
      dating from 1970 to 2001. The search terms were "bladder augmentation", "bladder
      substitution", "bladder autoaugmentation", "ureterocystoplasty" and "bladder
      engineering". The age group was "all child 0-18". DATA SELECTION: Articles
      selected were those with relevance to the scope of the topic. DATA EXTRACTION:
      The articles were analyzed with the primary focus being the problems encountered
      with various forms of urinary diversion, bladder augmentation and bladder
      replacement, and the subsequent evolution of materials and techniques. DATA
      SYNTHESIS: Bladder tissue may need to be replaced in the paediatric population
      because of congenital malformation, disease or trauma. The unique structure and
      function of urothelium and bladder muscle make this a challenging task.
      Management has evolved from a mindset of attempting to divert urine from the
      bladder completely to that of trying to preserve what is salvageable of the
      organ. Historically and contemporarily, the gastrointestinal tract has provided
      the raw material for urinary diversion, bladder augmentation and bladder
      substitution. Experience, however, has highlighted the potential complications
      inherent in the use of the bowel in the urinary tract including mucus production,
      stone disease, metabolic abnormalities, growth retardation, spontaneous
      perforation and malignancy. However, despite these drawbacks, the bowel is the
      gold standard in terms of functional utility and longevity. In efforts to develop
      alternatives, research has focused on the use of both natural and synthetic
      materials. With these materials, a whole new list of potential problems has been
      characterized. Tissue engineering may hold promise in resolving the issues of
      bladder replacement or repair by providing the necessary biocompatible raw
      material. CONCLUSIONS: Bowel segments have been and continue to be the clinically
      most useful material for urinary diversion, bladder augmentation and bladder
      replacement. Complications associated with the use of bowel in the urinary tract
      have prompted considerable research into alternative materials and methods.

PMID- 20046463
TI  - Enuresis: A maturational lag.
AB  - ENURESIS IS NOT A DISEASE, BUT A DISORDER CAUSED BY DELAYS IN THE MATURATION OF
      THREE PHYSIOLOGICAL PROCESSES: persistence of spontaneous bladder contractions,
      bladder volume exceeding the nocturnal functional bladder capacity and
      persistence of elevated sleep/arousal thresholds. Enuresis has been subtyped into
      two different groups, depending on whether the predominant feature is frequent
      small voidings (excessive bladder contractions) or large urinary volume (volume
      dependent). The clinical pattern demonstrated by the enuretic child depends on
      the severity of the maturational lag. In practice, a mix of these types is most
      common.

PMID- 20046464
TI  - The transplanted child: New immunosuppressive agents and the need for
      pharmacokinetic monitoring.
AB  - BACKGROUND: Pharmacokinetic monitoring has been insufficiently studied in
      paediatric solid organ transplantation, especially because some agents are
      relatively new to paediatric use, are of new formulation modification or are
      being used in combinations not previously well studied. The choice of
      immunosuppressive drugs after paediatric renal transplantation is increasing.
      Cyclosporine A (CyA), tacrolimus and mycophenolate mofetil (MMF) use has become
      routine. While pharmacokinetic monitoring of CyA and tacrolimus is routine, few
      paediatric data on tacrolimus pharmacokinetics exist, and, for MMF,
      pharmacokinetic monitoring is performed in only a few Canadian centres. The aim
      of the present article is to provide guidelines for the use of these three drugs
      by using a large number of full pharmacokinetic profiles in children. METHODS:
      One hundred forty-nine full pharmacokinetic 10-point profiles on cyclosporine
      microemulsion, 103 on the classic cyclosporine, 118 on tacrolimus and 114 on MMF
      were retrospectively analyzed. All pharmacokinetic profiles were obtained from
      paediatric renal transplant patients in steady state. RESULTS: For
      pharmacokinetic monitoring of the classic cyclosporine formulation, evaluation of
      the trough levels suffices to estimate the area under the curve (AUC). For
      microemulsified cyclosporine, the trough levels do not provide a useful tool, and
      blood concentrations at 2 or 3 h (C2 or C3) after intake should be measured
      instead. Tacrolimus trough levels sufficiently estimate the AUC, but measuring
      the C4 yields the best prediction of the AUC. Nonetheless, C2 also provides a
      superior tool than the trough levels. Tacrolimus and CyA AUCs change
      substantially over time after renal transplantation. There is only a poor
      correlation between the trough level and the AUC for mycophenolic acid (MPA). No
      single time point provides a surrogate marker of the AUC. At least three time
      points are required to accurately estimate the AUC, and C1, C2 and C6 serve as
      the best markers. The article also describes the interaction between MPA and
      differing concomitant immunosuppression, as well as the variation of the MPA AUC
      with differing concentrations of cyclosporine. CONCLUSIONS: Pharmacokinetic
      monitoring of these three drugs is mandatory in paediatric renal transplantation
      because it is impossible to predict the drug interactions and blood levels from a
      given dose. Target AUCs for a given time point after transplantation remain to be
      established.

PMID- 20046465
TI  - Hemolytic uremic syndrome: Events of the past decade.
AB  - This article describes the birth of the Canadian Pediatric Kidney Disease
      Research Centre (CPKDRC) in 1985 and the activities that have transpired as a
      result of collaborative research at paediatric centres across Canada. These
      include the National Retrospective Study of Childhood Hemolytic Uremic Syndrome
      (HUS), National Prospective Study of Risk Factors for Developing Escherichia coli
      O157:H7 Infection, and Intervention Studies for the Prevention of HUS. A look to
      the future describes possible studies to determine potential factors (surrogate
      markers) to identify children who are at risk for developing HUS following
      verotoxin-producing E coli gastroenteritis, other intervention studies and a more
      accurate understanding of permanent renal insufficiency in children who have had
      HUS.

PMID- 20046466
TI  - The adverse renal effects of prostaglandin-synthesis inhibition in the fetus and
      the newborn.
AB  - OBJECTIVES: To summarize experimental animal data and to provide a limited
      literature review on the adverse renal effects of nonsteroidal anti-inflammatory
      drugs (NSAIDs) on the developing fetus and the maturing newborn. DATA: The
      experimental data were obtained from anesthetized, ventilated, six- to eight-day
      old rabbits that received an intravenous bolus of either acetylsalicylic acid
      (ASA), ibuprofen (IBU) or indomethacin (INDO). In one set of experiments, ASA was
      also tested in 12-week-old (young adult) rabbits. Renal function was monitored
      with inulin and para-aminohippuric acid clearances measuring glomerular
      filtration rate (GFR) and renal blood flow. The renal vascular resistance was
      calculated. All three nonspecific cyclo-oxygenase-1 or -2 (COX-1/2) inhibitors
      caused remarkably similar reversible, oliguric, acute renal failure (ARF). In
      young adult animals, the side effects were attenuated. The underlying
      pathophysiology is related to the carefully maintained low GFR of the fetus and
      the newborn, dependent on a delicate interplay between vasoconstriction
      (angiotensin II) and vasodilation (prostaglandins [PGs]). When PG-synthesis is
      inhibited, the vasoconstriction is relatively unopposed, causing ARF. LITERATURE
      REVIEW: The renal effects of fetal exposure to NSAIDs are discussed, as are new
      insights into the role of COX-1/2 for a normal nephrogenesis. COX-nil or COX
      inhibited animals have long lasting renal structural injury. Fetuses exposed in
      utero to significant amounts of NSAIDs have at birth various degrees of renal
      insufficiency and structural renal defects with a very high mortality.
      CONCLUSIONS: All NSAIDs, both specific and nonspecific COX inhibitors, have renal
      side effects in the immediate post-natal period and should, therefore, be given
      with the utmost caution. NSAIDs given during pregnancy for the prevention of
      toxemia, polyhydramnios and premature labour may affect fetal renal function and
      structure. In animal experiments, IBU was not less nephrotoxic than INDO, as
      suggested recently by human premature neonates.

PMID- 20046467
TI  - Endoscopic injection therapy for treatment of vesicoureteric reflux: A 20-year
      perspective.
AB  - OBJECTIVE: To review the application and outcome of endoscopic injection therapy
      for vesicoureteric reflux in regard to its evolution over the past two decades.
      DATA SOURCES: Review articles, original reports and abstracts pertaining to
      endoscopic injection therapy were obtained through a PubMed search of English,
      German and French publications from 1981 to 2001. DATA SELECTION: A total of 46
      studies were selected. Four were selected to support basic concepts in the
      management of vesicoureteric reflux, and the remainder pertained specifically to
      endoscopic injection therapy for vesicoureteric reflux. DATA EXTRACTION: The
      reports were analyzed with focus on the physical properties of the biomaterial
      injected, results of treatment in regard to the cure of vesicoureteric reflux,
      duration of cure, and possible adverse effects and clinical benefits engendered
      by the use of injectable materials. DATA SYNTHESIS: Endoscopic injection therapy
      successfully cures vesicoureteric reflux in 60% to 80% of cases. Success rates
      are higher with particulate materials (Teflon and Macroplastique) than with
      bovine collagen or autologous chondrocytes. Long term data regarding cure are
      scant. Although concerns about particulate migration and autoimmune disease
      exist, these have not been borne out of clinical experience. Endoscopic injection
      may be accomplished on an outpatient basis, with less morbidity than with open
      ureteroneocystostomy. CONCLUSIONS: Endoscopic injection therapy should be offered
      as an alternative treatment in patients with indications to consider
      ureteroneocystotomy, but should not change the indications for surgical
      intervention. The ideal biomaterial for injection has yet to be developed, but
      the field of autologous tissue engineering holds promise for future development.

PMID- 20046468
TI  - Red blood cell transfusions in newborn infants: Revised guidelines.
AB  - In general, health care professionals taking care of high risk infants in
      neonatal intensive care units have become more restrictive in their use of red
      blood cell transfusion over the past 10 years. The present statement is intended
      for those caring for high risk newborn infants (preterm to one month of age). The
      objectives of this statement are to provide guidelines to reduce the incidence of
      anemia in preterm and term infants, to identify strategies to decrease the need
      for red blood cell transfusions and to limit donor exposure in this population.
      Recommendations for red blood cell transfusions are included.

PMID- 20046470
TI  - Fluoride and healthy teeth.

PMID- 20046469
TI  - The use of fluoride in infants and children.

PMID- 20046471
TI  - Vitamin K injection - best prevention for newborns.

PMID- 20046472
TI  - The value of aspiration cytology in cystic lesions of the maxillofacial region.
AB  - OBJECTIVES: The majority of the pathologic structures which are seen in the oral
      and maxillofacial region are either cystic or tend to show cystic changes. They
      may have not specific clinical and radiographic findings. Therefore, it is
      difficult to differentiate these lesions preoperatively. For this purpose, in
      this research, the value of fine-needle aspiration cytology (FNAC) in
      preoperative diagnosis was investigated by comparing with the postoperative
      histopathologic diagnosis. METHODS: One hundred aspirates from cystic lesions in
      the oral and maxillofacial region were included in this study. All of the samples
      except one were examined histopathologically and the results were compared.
      RESULTS: The results of the FNAC specimens obtained from 100 lesions were
      compared with histopathologic diagnosis of these lesions. According to these
      results, 12 insufficient (12%), 7 positive (7%), 81 negative (81%) specimens were
      obtained. Among these 88 lesions, 69 of them were diagnosed specifically by
      cytological examination (78.4%). 62 of the 69 specific diagnoses achieved by
      cytological examination were confirmed histopathologically (89.85%). The
      histological types of the seven lesions were missed by cytological examination.
      There were not any complications related with the fine-needle aspiration
      procedure in the research. CONCLUSIONS: According to these results, the value of
      fine-needle aspiration biopsy in cystic lesions of the maxillofacial region is
      found as successful as in the solid lesions.

PMID- 20046473
TI  - Composites associated with pulp-protection material: color-stability analysis
      after accelerated artificial aging.
AB  - OBJECTIVES: This study assessed the color stability of two composites associated
      with two pulp protectors submitted to accelerated artificial aging (AAA).
      METHODS: 60 test specimens were made with 0.5 mm of protection material (calcium
      hydroxide - CH or glass ionomer cement - GIC) and 2.5 mm of restoration material
      (Concept or QuixFil) and divided into 3 groups (n=10) according to the type of
      protection material/composite, and the control group (no protection). After
      polishing, color readings were obtained with a spectrophotometer (PCB 6807 Byk
      Gardner) before and after AAA for 384 hours, and L*, a*, and b* coordinates and
      total color variation (DeltaE) were analyzed (2-way ANOVA, Bonferroni, alpha=05).
      RESULTS: Composites placed on CH presented lower L* levels than those on GIC,
      which presented higher L* values than the control group and lower b* values than
      those of the CH group. The Concept composite presented higher DeltaE levels for
      all groups, differing statistically from QuixFil, except when placed on GIC.
      CONCLUSIONS: It was concluded that the protection material could affect the color
      stability and AAA is a factor that enhances this effect, depending on the type of
      composite used.

PMID- 20046474
TI  - The location and accessibility of the second mesiobuccal canal in maxillary first
      molar.
AB  - OBJECTIVES: The purpose of this study was to examine the location and
      accessibility of the second mesibuccal canal in maxillary first molar of a
      Turkish sub-population. METHODS: Presence and accessibility of the MB2 canal in
      110 extracted maxillary first molars was examined with unaided vision, dental
      loups and the DOM. To characterize the geometrical location of MB2 canals,
      photographs of pulp chambers were obtained. RESULTS: With the unaided vision, 58
      MB2 canal orifices and after evaluation with the dental loup, DOM an additional
      28 MB2 canal orifices were detected. In 65 molars, the MB2 canal orifices was
      located 0.87 mm distally and 1.73 mm palatally to the main mesiobuccal canal and
      in the remaining 21 molars was 0.72 mm mesially and 1.86 mm palatally.
      CONCLUSIONS: Presence of second mesiobuccal canal was similar to the other
      studies but in a Turkish sub-population it originates mainly distal to the main
      MB canal.

PMID- 20046475
TI  - Periapical status and quality of root fillings and coronal restorations in an
      adult Turkish subpopulation.
AB  - OBJECTIVES: To investigate the quality of root fillings and coronal restorations
      and their association with periapical status in an adult Turkish subpopulation.
      METHODS: A total of 400 subjects were examined. Panoramic radiographs of all
      participants and additional periapical radiographs of affected teeth were
      processed. The frequency of root canal treatment and the periapical status of all
      root filled teeth were evaluated. The relationship between the radiographic
      quality of root fillings and coronal restorations was examined by chi-squared
      statistical analysis. RESULTS: A total of 9460 teeth were examined. The total
      number of root filled teeth was 890 (9.39%), and 658 (73.9%) had apical
      periodontitis (AP). There was a significant correlation between the presence of
      periapical pathology and inadequate root canal fillings (P<.05). Presence of AP
      in root filled teeth was associated with inadequate adaptation of the filling
      (OR=1.097; P=0.54), and with poor radiographic quality of the coronal restoration
      (OR=0.91; P=0.70), and with poor radiographic quality of the filling restoration
      (OR=0.97; P=0.92). Only 24.5% of the root fillings were adequate. The highest
      percentage of root fillings was found in maxillary right first molars (6.9%).
      CONCLUSIONS: The results demonstrate a low prevalence of root-filled teeth and
      poor quality of coronal restorations and root fillings consistent with a high
      prevalence of apical periodontitis in a Turkish subpopulation.

PMID- 20046476
TI  - Effects of in-office and home bleaching gels on the surface mercury levels of
      dental amalgam.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of different in
      office and home bleaching gels on the surface mercury levels of dental amalgam.
      METHODS: Sixty disk-shaped amalgam specimens (GS-80, SDI- Australia) were
      prepared and randomly divided into the following treatment groups: 1. Distilled
      water (control); 2. 15% home-bleach carbamide peroxide (Opalescence PF, Ultra
      dent, USA) applied for 6 h/day for 3 weeks; and 3. 35% in-office bleach carbamide
      peroxide (Opalescence Quick, Ultradent) applied for 30 min/week for 3 weeks.
      Levels of mercury were measured as weight percentages using an energy dispersive
      x-ray micro-analyzer detector connected to an electron microscope. Data was
      analyzed using one-way ANOVA and a post hoc Tukey tests (P<.05). RESULTS: There
      were no significant differences between the surface mercury levels measured
      following treatment with the tested home-bleach and in-office bleach products
      (P=0.71). However, both materials yielded significantly more mercury levels than
      that of the control group (P<.001). CONCLUSIONS: The tested bleaching products
      significantly elevated the surface mercury levels of amalgam in vitro.

PMID- 20046477
TI  - TaqMan Real-Time Quantification of Epstein-Barr Virus in Severe Early Childhood
      Caries.
AB  - OBJECTIVES: Early childhood caries (ECC) has several risk factors and it is
      important stressful/painful events of childhood and immunosuppression may occur
      during this unique rampant caries pattern. The changes in the host immune
      competence by compromised cellular immune system functions can activate Epstein
      Barr virus (EBV). The objective of this study was to determine whether the
      supragingival plaque samples of severe-ECC (S-ECC) patients harbor more EBV load
      than the non-carious healthy children by quantitative TaqMan Real-Time polymerase
      chain reaction (PCR). METHODS: Sixty subjects, including 30 S-ECC patients as
      well as age and gender matched 30 caries-free patients were studied. The
      supragingival plaque samples were collected from patients by brushing their teeth
      for 1 minute and the toothbrush was washed in 1 ml of sterile deionized water.
      After viral DNA extraction, TaqMan real-time PCR assay was used to quantify EBV
      DNA. Dental treatments were completed for all S-ECC patients and they were called
      for routine controls. Only 10 treated S-ECC patients were come to the 3(rd)
      months' control and post-treatment viral sampling was made in the same manner.
      RESULTS: EBV DNA was detected 16 of 30 S-ECC patients and 6 of the healthy
      controls (P<.001). There was no relationship between baseline and post-treatment
      samples of 10 treated S-ECC patients. CONCLUSIONS: The results of the study
      suggest that oro-dental hygiene motives of S-ECC patients might be important
      contributory factor for S-ECC and EBV would not be involved in the
      etiopathogenesis of ECC.

PMID- 20046478
TI  - Monomer Release from Resin Based Dental Materials Cured With LED and Halogen
      Lights.
AB  - OBJECTIVES: To measure the release of TEGDMA and BisGMA from two commercially
      available composite resins; Filtek Z 250 (3M ESPE, Germany), Leaddent (Leaddent,
      Germany) and two fissure sealants; Helioseal F (3M ESPE, Germany) Enamel Loc
      (Premiere Rev, USA) over 1, 3 and 7 days after polymerization with standard
      quartz-tungsten halogen Coltolux II (QHL) (Coltene Switzerland) and a standard
      blue light emitting diode Elipar Freelight 2 (3M ESPE, Germany). METHODS: 9
      samples of each material were placed in disc shaped specimens in 1 mm of
      thickness and 10 mm in diameter (n=36). Each material was polymerized using LED
      for 20 s (n=12), 40 s (n=12) and halogen for 40 s (n=12), respectively. High
      Performance Liquid Chromatography (HPLC) was used to measure the amount of
      monomers released over 1, 3 and 7 days. Data was analyzed using one way ANOVA and
      Bonferroni test for multiple comparisons with a significance level of .05.
      RESULTS: LED 20 sec group showed the highest release of monomers at 1, 3 and 7
      days in sealant groups. Halogen 40 sec group resulted highest release of monomers
      for Leaddent at all time intervals (P<.05) CONCLUSIONS: Efficiency of the curing
      unit and applying the recommended curing time of the light activated resin based
      dental materials is very important to protect the patient from potential hazards
      of residual monomers.

PMID- 20046479
TI  - Re-Treatment Decisions for Failed Posterior Restorations among Dentists in
      Kuwait.
AB  - OBJECTIVES: To compare re-treatment choices for MOD amalgam or resin composite
      restorations with or without cusp fracture among dentists in Kuwait. METHODS: A
      random sample of 158 dentists completed a questionnaire designed to obtain socio
      demographic, educational and work-related information and their choices for re
      treatment of four scenarios of failed restorations on lower first molars: 1. MOD
      amalgam restoration; 2. MOD composite restoration; 3. MOD amalgam restoration
      with cuspal fracture; 4. MOD composite restoration with cuspal fracture. Re
      treatment options were: re-treating with amalgam; re-treating with composite;
      placing an onlay; or, placing a crown. For the purpose of analysis, responses
      were dichotomized into re-treatment with a direct or indirect restoration.
      RESULTS: For cases 1 and 2, most participants chose to re-treat with amalgam
      restoration and for cases 3 and 4, most chose to place an indirect restoration.
      In general, an increased tendency towards the indirect option was associated with
      increased age, being a male and being a specialist. Tendencies to place an
      indirect restoration did not differ between cases 1 and 2 (P=1.0) or cases 3 and
      4 (P=0.317), although the tendency to do so was significantly greater in case 3
      than 1 (P=0.000) and case 4 than 2 (P=0.000). CONCLUSIONS: The variation noted
      among dentists regarding their stated choices for re-treating failed posterior
      restorations appeared to be associated with gender, education and experience
      factors. A tendency towards indirect restorations was seen when the restoration
      is associated with a fractured cusp.

PMID- 20046480
TI  - Effects of delayed finishing/polishing on surface roughness, hardness and gloss
      of tooth-coloured restorative materials.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of delayed
      finishing/polishing on the surface roughness, hardness and gloss of tooth
      coloured restorative materials. METHODS: Four different tooth-coloured
      restoratives: a flowable resin composite- Tetric Flow, a hybrid resin composite-
      Venus, a nanohybrid resin composite- Grandio, and a polyacid modified resin
      composite- Dyract Extra were used. 30 specimens were made for each material and
      randomly assigned into three groups. The first group was finished/polished
      immediately and the second group was finished/polished after 24 hours. The
      remaining 10 specimens served as control. The surface roughness of each sample
      was recorded using a laser profilometer. Gloss measurements were performed using
      a small-area glossmeter. Vickers microhardness measurements were performed from
      three locations on each specimen surface under 100g load and 10s dwell time. Data
      for surface roughness and hardness were analyzed by Kruskal Wallis test and data
      for gloss were subjected to one-way ANOVA and Tukey test (P <.05). RESULTS: The
      smoothest surfaces were obtained under Mylar strip for all materials. While there
      were no significant differences in surface roughness of immediate and delayed
      finished/polished Dyract Extra samples, immediately finished/polished Venus and
      Grandio samples showed significantly higher roughness than the delayed polished
      samples (P <.05). In Tetric Flow samples, immediately finishing/polishing
      provided smoother surface than delayed finishing/polishing (P <.05). The highest
      gloss values were recorded under Mylar strip for all materials. While delayed
      finishing/polishing resulted in a significantly higher gloss compared to
      immediate finishing/polishing in Venus samples (P <.05), no differences were
      observed between delayed or immediate finishing/polishing for the other materials
      (P>.05). The lowest hardness values were found under Mylar strip. Delayed
      finishing/polishing significantly increased the hardness of all materials.
      CONCLUSIONS: The effect of delayed finishing/polishing on surface roughness,
      gloss and hardness appears to be material dependent.

PMID- 20046481
TI  - Clinical evaluation of resin-based composites in posterior restorations: 12-month
      results.
AB  - OBJECTIVES: The purpose of this study was to evaluate and compare the 12 month
      clinical performances of two different posterior composites in Class I and Class
      II restorations. METHODS: Thirty-one patients (10 male, 21 female) were recruited
      into the study. A total of 82 Class I and Class II cavities were restored with
      either a nanohybrid composite (Grandio) or a low-shrinkage composite (Quixfil),
      using their self etch adhesives (Futura Bond and Xeno III) according to
      manufacturers' instructions. The restorations were clinically evaluated 1 week
      after placement as baseline, and after 6 and 12 months post-operatively using
      modified USPHS criteria by two previously calibrated operators. Statistical
      analysis were performed using Pearson Chi-square and Fisher's Exact Test (P<.05).
      RESULTS: All patients attended the 12-month recall. Lack of retention was not
      observed in any of the restorations. With respect to color match, marginal
      adaptation, secondary caries and surface texture, no significant differences were
      found between two restorative materials tested after 12 months (P>.05). None of
      the restorations had marginal discoloration and anatomic form loss on the 12
      month follow-up. Restorations did not exhibit post-operative sensitivity at any
      evaluation period. CONCLUSIONS: Clinical assessment of nanohybrid (Grandio) and
      low-shrinkage posterior composite (Quixfil) exhibited good clinical results with
      predominating alpha scores after 12 months. However; further evaluations are
      necessary for the long-term clinical performance of these materials.

PMID- 20046482
TI  - Dental alloy sorting by the thermoelectric method.
AB  - OBJECTIVES: A nondestructive, rapid, and practical method of dental alloy sorting
      is desirable. In this study, the hypothesis to be tested is that dental alloys
      show significantly different and high thermoelectric power values, on the basis
      of which alloy sorting is possible. METHODS: Six silver-colored commercial dental
      casting alloys are used in this study: two silver alloys, one gold-silver
      palladium alloy, one cobalt-chromium alloy, one nickel-chromium alloy, and one
      titanium alloy. The thermoelectric power of their castings was determined against
      constantan using a simple apparatus developed in a previous study. Linear least
      square fitting was applied to the measured thermal-EMF-temperature curve to
      determine the thermoelectric power for the temperature ranges of 298-303 K
      (temperature difference Deltat = 5 K), 298-308 K (Deltat=10 K), 298-313 K
      (Deltat=15 K), and 298-318 K (Deltat=20 K). The results were analyzed using one
      way ANOVA and by the Scheffe's test at a significance level of alpha=0.01.
      RESULTS: When the temperature difference was 10 K or less, the difference in the
      thermoelectric powers of the alloys was not always statistically significant.
      However, when the temperature difference was 15 K or more, the thermoelectric
      powers of the six alloys differed significantly. CONCLUSIONS: The results
      indicated the feasibility of rapid sorting of specific dental alloys by the
      thermoelectric method, provided a sufficiently large temperature difference is
      achieved.

PMID- 20046483
TI  - Implant-retained auricular prosthesis: a case report.
AB  - Extraoral implant retained prosthesis have been proven to be a predictable
      treatment option for maxillofacial rehabilitation. This case report describes the
      clinical and laboratory procedures for fabricating an auricular prosthesis.In
      this case report, an auricular prosthesis was fabricated for a patient who lost
      the left and right external ear in an electrical burn. Extraoral implants and bar
      and-clip retention for the proper connection of the auricular prosthesis to
      implant were used. This prosthesis was acceptable to the patient because of
      excellent support, retentive abilities and the patient's appearance.

PMID- 20046484
TI  - A talon cusp on fused teeth associated with hypodontia: report of a unique case.
AB  - Fusion and talon cusps are rare developmental dental anomalies affecting both
      primary and permanent dentitions. Talon cusps normally occur on the palatal
      surface of permanent maxillary incisors, while fused teeth are more common in the
      primary anterior dentition. An understanding of these dental anomalies and their
      associated problems are important to provide prophylactic measures, thereby
      preventing or minimizing possible complications. This paper presents a unique
      case of fused mandibular permanent incisors with a lingual talon cusp associated
      with hypodontia of an adjacent tooth.

PMID- 20046485
TI  - Prosthetic rehabilitation of velopharyngeal insufficiency: pharyngeal obturator
      prostheses with different retention mechanisms.
AB  - Pharyngeal obturator prostheses restore the congenital or acquired defects of the
      soft palate and allow adequate closure of palatopharyngeal sphincter. Two
      patients with soft palate defect and subsequent velopharyngeal insufficiency were
      rehabilitated using pharyngeal obturator prostheses which had different retention
      mechanisms. Since it is necessary for swallowing and intelligible speech, the
      patients were examined in terms of adequate velopharyngeal closure after
      prosthetic treatment. The results were satisfying for both the patients and
      physicians.

PMID- 20046486
TI  - Garlic burn in a patient with trigeminal neuralgia: a case report.
AB  - Garlic is an herb which has been used by many cultures for treating various
      health problems for centuries. Uncontrolled use of herbal remedies, known as
      alternative treatment methods, may lead to side effects and serious treatment
      complications. This study aimed to draw attention to complications related to
      alternative treatment methods and to review the literature in the light of this
      case.A female patient who had been treated for trigeminal neuralgia was admitted
      to our clinic complaining of severe pain on the left side of her face. In
      anamnesis, the patient reported that she had applied garlic topically to this
      region. Extraoral examination revealed a broad cutaneous burn on the same region.
      According to a dermatology consultation, a treatment for cutaneous burns was
      applied and severe trigeminal neuralgia pain was eliminated with glycerol
      injection by an oral and maxillofacial surgeon.

PMID- 20046487
TI  - Osteochondroma of the coronoid process and joint formation with zygomatic arch
      (jacob disease): report of a case.
AB  - Jacob disease is a rare condition consisting of pseudo joint formation between
      enlarged mandibular coronoid process and the inner surface of the zygoma. We
      report a 16-years-old male patient with Jacob disease who presented with
      restricted mouth opening and swelling of the right zygoma. In this report,
      clinical, radiological, and histopathological findings of the Jacob disease and
      its surgical approach are discussed.

PMID- 20046488
TI  - Xeroradiography: stagnated after a promising beginning? A historical review.
AB  - Various methods have been introduced for obtaining radiographs. Xeroradiography
      which is a method of imaging uses the xeroradiographic copying process to record
      images produced by diagnostic x-rays. It differs from halide film technique in
      that it involves neither wet chemical processing nor the use of dark room.
      Literature on this subject is scarce. After an initial promising beginning, this
      imaging method, once thought to hold the key to endodontic imaging, got
      stagnated. A revisit of this promising endodontic imaging system would therefore
      be appropriate. The purpose of this study was to review xeroradiographic
      technique as a roentgenographic imaging system.

PMID- 20046490
TI  - State-of-the-art CT imaging techniques for congenital heart disease.
AB  - CT is increasingly being used for evaluating the cardiovascular structures and
      airways in the patients with congenital heart disease. Multi-slice CT has
      traditionally been used for the evaluation of the extracardiac vascular and
      airway abnormalities because of its inherent high spatial resolution and
      excellent air-tissue contrast. Recent developments in CT technology primarily by
      reducing the cardiac motion and the radiation dose usage in congenital heart
      disease evaluation have helped expand the indications for CT usage.
      Tracheobronchomalacia associated with congenital heart disease can be evaluated
      with cine CT. Intravenous contrast injection should be tailored to unequivocally
      demonstrate cardiovascular abnormalities. Knowledge of the state-of-the-art CT
      imaging techniques that are used for evaluating congenital heart disease is
      helpful not only for planning and performing CT examinations, but also for
      interpreting and presenting the CT image findings that consequently guide the
      proper medical and surgical management.

PMID- 20046491
TI  - Fluid attenuated inversion recovery (FLAIR) imaging of the normal brain:
      comparisons between under the conditions of 3.0 Tesla and 1.5 Tesla.
AB  - OBJECTIVE: The aim of this study was to evaluate the differences in normal brain
      MRI findings between under 3.0 Tesla (T) and 1.5T MRI conditions with the use of
      the fluid attenuated inversion recovery (FLAIR) sequences. MATERIALS AND METHODS:
      Eleven normal adults underwent imaging with the use of the FLAIR sequences on
      both 1.5T and 3.0T scanners. Two neuroradiologists compared the signal intensity
      (SI) of the centrum semiovale (CS), pulvinar thalami (PT) and normal iron deposit
      structures (IDSs) on the 3.0T and 1.5T FLAIR images, and they evaluated three MRI
      findings qualitatively: high SI of CS; low SI of PT; low SI of IDS. We also
      evaluated signal-to-noise ratios (SNRs) for the CS, PT, red nucleus and
      cerebellar dentate nucleus on the FLAIR images. RESULTS: Based on qualitative
      analyses, the 3.0T FLAIR images showed all three MRI findings for all cases. Low
      SI for the PT in seven cases (64%), high SI of the CS in one case (9%) and low SI
      of the cerebellar dentate nucleus in one case (9%) were visualized only on 3.0T
      FLAIR images. The mean SNRs of the PT, red nucleus and dentate nucleus in
      patients where 3.0T FLAIR imaging was performed were significantly lower as
      compared with the SNRs on 1.5T FLAIR images. The SNR of the CS was not
      significantly different between under the two magnetic field strengths (p >
      0.05). CONCLUSION: We have demonstrated that normal, high and low SIs of the CS,
      PT and IDS on 3.0T FLAIR images were depicted more frequently and more
      prominently as compared with those on 1.5T FLAIR images in normal adult brains.

PMID- 20046492
TI  - Gray, white matter concentration changes and their correlation with heterotopic
      neurons in temporal lobe epilepsy.
AB  - OBJECTIVE: To identify changes in gray and white matter concentrations (GMC,
      WMC), and their relation to heterotopic neuron numbers in mesial temporal lobe
      epilepsy (mTLE). MATERIALS AND METHODS: The gray matter or white matter
      concentrations of 16 left and 15 right mTLE patients who achieved an excellent
      surgical outcome were compared with those of 24 healthy volunteers for the left
      group and with 23 healthy volunteers for the right group, by optimized voxel
      based morphometry using unmodulated and modulated images. A histologic count of
      heterotopic neurons was obtained in the white matter of the anterior temporal
      lobe originating from the patients' surgical specimens. In addition, the number
      of heterotopic neurons were tested to determine if there was a correlation with
      the GMC or WMC. RESULTS: The GMCs of the left and right mTLE groups were reduced
      in the ipsilateral hippocampi, bilateral thalami, precentral gyri, and in the
      cerebellum. The WMCs were reduced in the ipsilateral white matter of the anterior
      temporal lobe, bilateral parahippocampal gyri, and internal capsules, but
      increased in the pons and bilateral precentral gyri. The heterotopic neuron
      counts in the left mTLE group showed a positive correlation (r = 0.819, p <
      0.0001) with GMCs and a negative correlation (r = -0.839, p < 0.0001) with WMCs
      in the white matter of the anterior temporal lobe. CONCLUSION: The present study
      shows the abnormalities of the cortico-thalamo-hippocampal network including a
      gray matter volume reduction in the anterior frontal lobes and an abnormality of
      brain tissue concentration in the pontine area. Furthermore, heterotopic neuron
      numbers were significantly correlated with GMC or WMC in the left white matter of
      anterior temporal lobe.

PMID- 20046493
TI  - The clinical feasibility of using non-breath-hold real-time MR-echo imaging for
      the evaluation of mediastinal and chest wall tumor invasion.
AB  - OBJECTIVE: We wanted to determine the clinical feasibility of using non-breath
      hold real-time MR-echo imaging for the evaluation of mediastinal and chest wall
      tumor invasion. MATERIALS AND METHODS: MR-echo imaging was prospectively applied
      to 45 structures in 22 patients who had non-small cell lung cancer when the tumor
      invasion was indeterminate on CT. The static MR imaging alone, and the static MR
      imaging combined with MR-echo examinations were analyzed. The surgical and
      pathological findings were compared with using the Wilcoxon-signed rank test and
      McNemar's test. RESULTS: The accuracy, sensitivity and specificity of the
      combined MR-echo examination and static MR imaging for determining the presence
      of invasion were 84%, 83% and 85%, respectively, for the first reading session
      and they were 87%, 83% and 87%, respectively, for the second reading session
      (there was substantial interobserver agreement, k = 0.74). For the static MR
      imaging alone, these values were 62%, 83% and 59%, respectively, for the first
      reader and they were 69%, 67% and 74%, respectively, for the second reader (there
      was moderate interobserver agreement, k = 0.49). The diagnostic confidence for
      tumor invasion was also higher for the combined MR-echo examination and static MR
      imaging than that for the static MR imaging alone (p < 0.05). CONCLUSION: The
      combined reading of a non-breath-hold real-time MR-echo examination and static MR
      imaging provides higher specificity and diagnostic confidence than those for the
      static MR imaging reading alone to determine the presence of mediastinal or chest
      wall tumor invasion when this was indeterminate on CT scanning.

PMID- 20046494
TI  - Is weight-based adjustment of automatic exposure control necessary for the
      reduction of chest CT radiation dose?
AB  - OBJECTIVE: To assess the effects of radiation dose reduction in the chest CT
      using a weight-based adjustment of the automatic exposure control (AEC)
      technique. MATERIALS AND METHODS: With Institutional Review Board Approval, 60
      patients (mean age, 59.1 years; M:F = 35:25) and 57 weight-matched patients (mean
      age, 52.3 years, M:F = 25:32) were scanned using a weight-adjusted AEC and non
      weight-adjusted AEC, respectively on a 64-slice multidetector CT with a 0.984:1
      pitch, 0.5 second rotation time, 40 mm table feed/rotation, and 2.5 mm section
      thickness. Patients were categorized into 3 weight categories; < 60 kg (n = 17),
      60-90 kg (n = 52), and > 90 kg (n = 48). Patient weights, scanning parameters, CT
      dose index volumes (CTDIvol) and dose length product (DLP) were recorded, while
      effective dose (ED) was estimated. Image noise was measured in the descending
      thoracic aorta. Data were analyzed using a standard statistical package
      (SAS/STAT) (Version 9.1, SAS institute Inc, Cary, NC). RESULTS: Compared to the
      non-weight-adjusted AEC, the weight-adjusted AEC technique resulted in an average
      decrease of 29% in CTDIvol and a 27% effective dose reduction (p < 0.0001). With
      weight-adjusted AEC, the CTDIvol decreased to 15.8, 15.9, and 27.3 mGy for the <
      60, 60-90 and > 91 kg weight groups, respectively, compared to 20.3, 27.9 and
      32.8 mGy, with non-weight-adjusted AEC. No significant difference was observed
      for objective image noise between the chest CT acquired with the non-weight
      adjusted (15.0 +/- 3.1) and weight-adjusted (16.1 +/- 5.6) AEC techniques (p >
      0.05). CONCLUSION: The results of this study suggest that AEC should be tailored
      according to patient weight. Without weight-based adjustment of AEC, patients are
      exposed to a 17 - 43% higher radiation-dose from a chest CT.

PMID- 20046495
TI  - High-resolution diffusion tensor MR imaging for evaluating myocardial anisotropy
      and fiber tracking at 3T: the effect of the number of diffusion-sensitizing
      gradient directions.
AB  - OBJECTIVE: We wanted to evaluate the effect of the number of diffusion
      sensitizing gradient directions on the image quality for evaluating myocardial
      anisotropy and fiber tracking by using in vitro diffusion tensor MR imaging (DT
      MRI). MATERIALS AND METHODS: The DT-MR images, using a SENSE-based echoplanar
      imaging technique, were acquired from ten excised porcine hearts by using a 3T MR
      scanner. With a b-value of 800 s/mm(2), the diffusion tensor images were obtained
      for 6, 15 and 32 diffusion-sensitizing gradient directions at the midventricular
      level. The number of tracked fibers, the fractional anisotropy (FA), and the
      length of the tracked fibers were measured for the quantitative analysis. Two
      radiologists assessed the image quality of the fiber tractography for the
      qualitative analysis. RESULTS: By increasing the number of diffusion-sensitizing
      gradient directions from 6 to 15, and then to 32, the FA and standard deviation
      were significantly reduced (p < 0.01), and the number of tracked fibers and the
      length of the tracked fibers were significantly increased (p < 0.01). The image
      quality of the fiber tractography was significantly increased with the increased
      number of diffusion-sensitizing gradient directions (p < 0.01). CONCLUSION: The
      image quality of in vitro DT-MRI is significantly improved as the number of
      diffusion-sensitizing gradient directions is increased.

PMID- 20046496
TI  - Incidental non-cardiac findings of a coronary angiography with a 128-slice multi
      detector CT scanner: should we only concentrate on the heart?
AB  - OBJECTIVE: To evaluate the spectrum, prevalence, and significance of incidental
      non-cardiac findings (INCF) in patients referred for a non-invasive coronary
      angiography using a 128-slice multi-detector CT (MDCT). MATERIALS AND METHODS:
      The study subjects included 1,044 patients; 774 males (mean age, 59.9 years) and
      270 females (mean age, 63 years), referred for a coronary CT angiography on a 128
      slice MDCT scanner. The scans were acquired from the level of the carina to just
      below the diaphragm. To evaluate INCFs, images were reconstructed with a large
      field of view (> 300 mm) covering the entire thorax. Images were reviewed in the
      axial, coronal, and sagittal planes, using the mediastinal, lung, and bone
      windows. The INCFs were classified as severe, indeterminate, and mild, based on
      their clinical importance, and as thoracic or abdominal based on their locations.
      RESULTS: Incidental non-cardiac findings were detected in 56% of patients (588 of
      1,044), including 435 males (mean age, 65.6 years) and 153 females (mean age,
      67.9 years). A total of 729 INCFs were observed: 459 (63%) mild (58% thoracic,
      43% abdominal), 96 (13%) indeterminate (95% thoracic, 5% abdominal), and 174
      (24%) severe (87% thoracic, 13% abdominal). The prevalence of severe INCFs was
      15%. Two severe INCFs were histologically verified as lung cancers. CONCLUSION:
      The 128-slice MDCT coronary angiography, in addition to cardiac imaging, can
      provide important information on the pathology of the chest and upper abdomen.
      The presence of severe INCFs is not rare, especially in the thorax. Therefore,
      all organs in the scan should be thoroughly evaluated in daily clinical practice.

PMID- 20046497
TI  - CT findings of completely regressed hepatocellular carcinoma with main portal
      vein tumor thrombosis after transcatheter arterial chemoembolization.
AB  - OBJECTIVE: The objective of this study was to determine the sequential CT
      findings of controlled hepatocellular carcinoma (HCC) with main portal vein (MPV)
      thrombosis with the use of transcatheter arterial chemoembolization and
      additional intra-arterial cisplatin infusion. MATERIALS AND METHODS: From January
      2004 to September 2006, 138 patients with HCC invading MPV were referred to the
      angiography unit of our institution for chemoembolization and additional intra
      arterial cisplatin infusion. Until August 2008, seven (5%) of 138 patients were
      followed-up and found not to have tumor recurrence. CT scans were retrospectively
      reviewed by two radiologists, focusing on the following parameters: the extent of
      portal vein thrombosis, the diameter of the affected portal vein, and enhancement
      of portal vein thrombosis. RESULTS: THE EXTENT OF PORTAL VEIN THROMBOSIS AT THE
      INITIAL PRESENTATION WAS VARIABLE: left portal vein (LPV) and MPV (n = 1), right
      portal vein (RPV) and MPV (n = 3), as well as RPV, LPV and MPV (n = 3). The
      extent and diameter of the affected portal vein decreased during follow-up
      examinations. In addition, the degree of enhancement for tumor thrombi and serum
      alpha-feto-protein levels decreased after the transcatheter arterial
      chemoembolization. Portal vein thrombosis was found to be completely resolved in
      one patient, whereas residual thrombus without viability was persistent in six
      patients. CONCLUSION: If chemoembolization is effective in patients with HCC that
      invades the portal vein, the extent and enhancement of portal vein thrombosis is
      reduced, but residual thrombosis frequently persists for months or years, without
      evidence of a viable tumor.

PMID- 20046498
TI  - Contrast-enhanced harmonic ultrasonography for the assessment of prostate cancer
      aggressiveness: a preliminary study.
AB  - OBJECTIVE: To determine whether contrast-enhanced harmonic ultrasonography can be
      used to predict the aggressiveness of prostate cancer. MATERIALS AND METHODS:
      Contrast-enhanced harmonic ultrasonography was performed in 103 patients
      suspected of prostate cancer before biopsy. Time intensity curves were
      reconstructed for systematic biopsy sites and sonographic abnormalities. The
      characteristics of the curves were described using hemodynamic indices including
      arrival time (AT), time-to-peak (TTP), and peak intensity (PI). The differences
      of hemodynamic indices between high-grade and low-grade cancer were analyzed and
      the correlations between the hemodynamic indices and biopsy Gleason score were
      studied. RESULTS: Prostate cancer was detected in 41 of 103 patients and there
      were significant differences in the hemodynamic indices between the biopsy sites
      of the non-malignant patients and prostate cancer lesions (p < 0.05). The
      prostate biopsies revealed 154 prostate cancer lesions, including 31 low-grade
      lesions and 123 high-grade lesions. The hemodynamic indices AT and TTP of high
      grade tumors were significantly shorter than those of low-grade tumors (p =
      0.001, 0.002). In addition, high-grade peripheral zone (PZ) tumors had higher PI
      than low-grade PZ tumors (p = 0.009). The PZ prostate cancer Gleason score
      correlated with PI, AT and TTP, with Spearman correlation coefficients of 0.223, 
      0.335, and -0.351, respectively (p = 0.013, < 0.001 and < 0.001). CONCLUSION:
      Contrast-enhanced ultrasound measurements of hemodynamic indices correlate with
      the prostate cancer Gleason score.

PMID- 20046499
TI  - Ultrasound diagnosis of either an occult or missed fracture of an extremity in
      pediatric-aged children.
AB  - OBJECTIVE: To report and assess the usefulness of ultrasound (US) findings for
      occult fractures of growing bones. MATERIALS AND METHODS: For six years, US scans
      were performed in children younger than 15 years who were referred with trauma
      related local pain and swelling of the extremities. As a routine US examination,
      the soft tissue, bones, and adjacent joints were examined in the area of
      discomfort, in addition to the asymptomatic contralateral extremity for
      comparison. Twenty-five occult fractures in 25 children (age range, five months
      15 years; average age, 7.7 years) were confirmed by initial and follow-up
      radiograms, additional imaging studies, and clinical observation longer than
      three weeks. RESULTS: The most common site of occult fractures was the elbow (n =
      9, 36%), followed by the knee (n = 7, 28%), ischium (n = 4, 16%), distal fibula
      (n = 3, 12%), proximal femur (n = 1, 4%), and humeral shaft (n = 1, 4%). On the
      retrograde review of the routine radiographs, 13 out of the 25 cases showed no
      bone abnormalities except for various soft tissue swelling. For the US findings,
      cortical discontinuity (direct sign of a fracture) was clearly visualized in 23
      cases (92%) and was questionable in two (8%). As auxiliary US findings (indirect
      signs of a fracture), step-off deformities, tiny avulsed bone fragments, double
      line appearance of cortical margins, and diffuse irregularity of the bone
      surfaces were identified. CONCLUSION: Performing US for soft tissue and bone
      surfaces with pain and swelling, with or without trauma history in the
      extremities, is important for diagnosing occult or missed fractures of immature
      bones in pediatric-aged children.

PMID- 20046500
TI  - Fenestrated stent graft repair of abdominal aortic aneurysm: hemodynamic analysis
      of the effect of fenestrated stents on the renal arteries.
AB  - OBJECTIVE: We wanted to investigate the hemodynamic effect of fenestrated stents
      on the renal arteries with using a fluid structure interaction method. MATERIALS
      AND METHODS: Two representative patients who each had abdominal aortic aneurysm
      that was treated with fenestrated stent grafts were selected for the study. 3D
      realistic aorta models for the main artery branches and aneurysm were generated
      based on the multislice CT scans from two patients with different aortic
      geometries. The simulated fenestrated stents were designed and modelled based on
      the 3D intraluminal appearance, and these were placed inside the renal artery
      with an intra-aortic protrusion of 5.0-7.0 mm to reflect the actual patients'
      treatment. The stent wire thickness was simulated with a diameter of 0.4 mm and
      hemodynamic analysis was performed at different cardiac cycles. RESULTS: Our
      results showed that the effect of the fenestrated stent wires on the renal blood
      flow was minimal because the flow velocity was not significantly affected when
      compared to that calculated at pre-stent graft implantation, and this was despite
      the presence of recirculation patterns at the proximal part of the renal
      arteries. The wall pressure was found to be significantly decreased after
      fenestration, yet no significant change of the wall shear stress was noticed at
      post-fenestration, although the wall shear stress was shown to decrease slightly
      at the proximal aneurysm necks. CONCLUSION: Our analysis demonstrates that the
      hemodynamic effect of fenestrated renal stents on the renal arteries is
      insignificant. Further studies are needed to investigate the effect of different
      lengths of stent protrusion with variable stent thicknesses on the renal blood
      flow, and this is valuable for understanding the long-term outcomes of
      fenestrated repair.

PMID- 20046501
TI  - Percutaneous transabdominal approach for the treatment of endoleaks after
      endovascular repair of infrarenal abdominal aortic aneurysm.
AB  - OBJECTIVE: The purpose of this study was to evaluate the technical feasibility
      and clinical efficacy of percutaneous transabdominal treatment of endoleaks after
      endovascular aneurysm repair. MATERIALS AND METHODS: Between 2000 and 2007, six
      patients with type I (n = 4) or II (n = 2) endoleaks were treated by the
      percutaneous transabdominal approach using embolization with N-butyl
      cyanoacrylate with or without coils. Five patients underwent a single session and
      one patient had two sessions of embolization. The median time between aneurysm
      repair and endoleak treatment was 25.5 months (range: 0-84 months). Follow-up CT
      images were evaluated for changes in the size and shape of the aneurysm sac and
      presence or resolution of endoleaks. The median follow-up after endoleak
      treatment was 16.4 months (range: 0-37 months) RESULTS: Technical success was
      achieved in all six patients. Clinical success was achieved in four patients with
      complete resolution of the endoleak confirmed by follow-up CT. Clinical failure
      was observed in two patients. One eventually underwent surgical conversion, and
      the other was lost to follow-up. There were no procedure-related complications.
      CONCLUSION: The percutaneous transabdominal approach for the treatment of type I
      or II endoleaks, after endovascular aneurysm repair, is an alternative method
      when conventional endovascular methods have failed.

PMID- 20046502
TI  - Lymphangiomatosis involving the inferior vena cava, heart, pulmonary artery and
      pelvic cavity.
AB  - A 38-year-old woman who had undergone pelvic lymphangioma resection two months
      previously presented with cough and dyspnea. Transthoracic echocardiography and
      CT demonstrated the presence of a mixed cystic/solid component tumor involving
      the inferior vena cava, heart and pulmonary artery. Complete resection of the
      cardiac tumor was performed and lymphangioma was confirmed based on
      histopathologic examination. To the best of our knowledge, this is the first
      report of lymphangiomatosis with cardiac and pelvic involvement in the published
      clinical literature.

PMID- 20046503
TI  - Prenatal diagnosis of bilateral pulmonary agenesis: a case report.
AB  - We report a case of bilateral pulmonary agenesis (BPA), which was suspected
      during a prenatal US examination and diagnosed by fetal magnetic resonance
      imaging (MRI). BPA is an extremely rare congenital anomaly and, although many
      fetal structural defects can be detected with a high degree of confidence after
      introducing high-resolution US, the prenatal diagnosis of BPA remains
      problematic. Other thoracic abnormalities, such as a congenital diaphragmatic
      hernia, congenital cystic adenomatoid malformation, and pulmonary sequestration,
      should be excluded from the list of possible diagnoses before coming to the
      conclusion of BPA, because BPA is absolutely incompatible with extrauterine life,
      and an accurate internal diagnosis can prevent a futile intervention from being
      performed.

PMID- 20046504
TI  - Incidental detection of interstitial pregnancy on CT imaging.
AB  - Ectopic pregnancy is a potentially life-threatening condition. Detection of
      ectopic pregnancy on CT images is rare. In this case, we describe the CT findings
      of interstitial pregnancy both before and after rupture. If CT images demonstrate
      the presence of a strong enhancing ring-like mass in the pelvis, ectopic
      pregnancy should be considered.

PMID- 20046505
TI  - MDCT and Gd-EOB-DTPA enhanced MRI findings of adrenal adenoma arising from an
      ectopic adrenal gland within the liver: radiologic-pathologic correlation.
AB  - We report a case of an adenoma arising from an ectopic adrenal gland mimicking a
      hepatocellular carcinoma in a heavy alcohol abuser. A MDCT showed a 2.7 low
      attenuating nodule in segment VII of the liver through all CT phases. Compared to
      a precontrast image, however, a subtle enhancement was noted on the arterial
      phase CT image. On T1 weighted in- and opposed-phase MR images, an abundant fat
      component within the lesion was seen. Dynamic contrast-enhanced MR images after
      administration of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd
      EOB-DTPA) more clearly depicted hypervascularity and wash-out of the lesion on
      arterial and portal phases, respectively. On delayed hepatobiliary phase MR
      images, obtained 20 minutes after Gd-EOB-DTPA administration, subtle uptake or
      retention of the contrast agent by the lesion was suspected. A tumorectomy was
      performed and adrenal adenoma from an ectopic adrenal gland within the liver was
      confirmed.

PMID- 20046507
TI  - The role of monoclonal antibody in combination with first-line chemotherapy in
      Asian patients with advanced non-small cell lung cancer.
AB  - The strategies of incorporating monoclonal antibodies (MoABs) have now proved
      efficacy in the first-line treatment of advanced non-small cell lung cancer
      (NSCLC). These include targeting the vascular endothelial growth factor (VEGF) or
      epidermal growth factor receptor (EGFR). Bevacizumab is a MoAB targeting the
      vascular endothelial growth factor (VEGF), an important mediator of new blood
      vessel formation. Cetuximab is a MoAB directed at EGFR. Binding cetuximab to EGFR
      blocks signal transduction and promotes receptor internalization and degradation.
      In this review, we present current data of bevacizumab and cetuximab for the
      first line treatment of advanced NSCLC. We also refer to their potential for
      Asian patients with advanced NSCLC in the first-line setting.

PMID- 20046509
TI  - Early initiation of alcohol drinking, cigarette smoking, and sexual intercourse
      linked to suicidal ideation and attempts: findings from the 2006 Korean Youth
      Risk Behavior Survey.
AB  - PURPOSE: This study examined the association between early initiation of problem
      behaviors (alcohol drinking, cigarette smoking, and sexual intercourse) and
      suicidal behaviors (suicidal ideation and suicide attempts), and explored the
      effect of concurrent participation in these problem behaviors on suicidal
      behaviors among Korean adolescent males and females. MATERIALS AND METHODS: Data
      were obtained from the 2006 Korean Youth Risk Behavior Survey, a nationally
      representative sample of middle and high school students (32,417 males and 31,467
      females) in grades seven through twelve. Bivariate and multivariate logistic
      analyses were conducted. Several important covariates, such as age, family living
      structure, household economic status, academic performance, current alcohol
      drinking, current cigarette smoking, current butane gas or glue sniffing,
      perceived body weight, unhealthy weight control behaviors, subjective sleep
      evaluation, and depressed mood were included in the analyses. RESULTS: Both male
      and female preteen initiators of each problem behavior were at greater risk for
      suicidal behaviors than non-initiators, even after controlling for covariates.
      More numerous concurrent problematic behaviors were correlated with greater
      likelihood of seriously considering or attempting suicide among both males and
      females. This pattern was more clearly observed in preteen than in teen
      initiators although the former and latter were engaged in the same frequency of
      problem behavior. CONCLUSION: Early initiation of alcohol drinking, cigarette
      smoking, and sexual intercourse, particularly among preteens, represented an
      important predictor of later suicidal ideation and suicide attempts in both
      genders. Thus, early preventive intervention programs should be developed and may
      reduce the potential risks for subsequent suicidal behaviors.

PMID- 20046508
TI  - Intrinsic cellular defenses against virus infection by antiviral type I
      interferon.
AB  - Intrinsic cellular defenses are non-specific antiviral activities by recognizing
      pathogen-associated molecular patterns (PAMPs). Toll-like receptors (TLRs), one
      of the pathogen recognize receptor (PRR), sense various microbial ligands.
      Especially, TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 recognize viral ligands such as
      glycoprotein, single- or double-stranded RNA and CpG nucleotides. The binding of
      viral ligands to TLRs transmits its signal to Toll/interleukin-1 receptor (TIR)
      to activate transcription factors via signal transduction pathway. Through
      activation of transcription factors, such as interferon regulatory factor-3, 5,
      and 7 (IRF-3, 5, 7) or nuclear factor-kappaB (NF-kappaB), type I interferons are
      induced, and antiviral proteins such as myxovirus-resistance protein (Mx) GTPase,
      RNA-dependent Protein Kinase (PKR), ribonuclease L (RNase L), Oligo-adenylate
      Synthetase (OAS) and Interferon Stimulated Gene (ISG) are further expressed.
      These antiviral proteins play an important role of antiviral resistancy against
      several viral pathogens in infected cells and further activate innate immune
      responses.

PMID- 20046510
TI  - No evidence of an association between A218C polymorphism of the tryptophan
      hydroxylase 1 gene and aggression in schizophrenia in a Korean population.
AB  - PURPOSE: We investigated the association between the tryptohan hydroxylase 1
      (TPH1) gene and aggression in schizophrenia in a Korean population. MATERIALS AND
      METHODS: The sample included 61 aggressive patients as well as 104 non-aggressive
      patients from psychiatric hospitals and 335 healthy volunteers in Korea. Blood
      samples were collected from all participants for TPH1 A218C genotyping. The
      patients were administered standard psychiatric interviews as well as a self
      report questionnaire for anger-related traits. RESULTS: In the case-control
      phenotypic comparisons, there was no significant association between the
      aggressive patients and the TPH1 A218C polymorphism. There was no significant
      effect of the TPH1 genotype on the anger-related traits, or no significant
      interaction between the genotype and group (aggressive and non-aggressive
      patients). CONCLUSION: These findings suggest that TPH1 does not play a major
      role in aggressive behavior via anger in schizophrenic patients.

PMID- 20046511
TI  - Endoscopic evaluation of gastric emptying and effect of mosapride citrate on
      gastric emptying.
AB  - PURPOSE: Gastric emptying has been evaluated by scintigraphy in spite of its
      limitations of time consumption, cost, and danger of radioisotope. Endoscopy is a
      simple technique, however, its validation for gastric emptying and quantification
      of food has not yet been investigated. The aim of our study was to assess
      endoscopic gastric emptying compared with scintigraphy and radiopaque markers
      (ROMs) studies. We also investigated the effect of a single dose of mosapride on
      gastric emptying. MATERIALS AND METHODS: Fifteen healthy volunteers underwent
      scintigraphy. Next day, subjects received a standard solid meal with ROMs and
      underwent endoscopy and simple abdomen X-ray after 3 hrs. After one week, the
      same procedure was repeated after ingestion of mosapride (5 mg for group 1, n =
      8; 10 mg for group 2, n = 7) 15 min before the meal. Quantification of gastric
      residue by endoscopy was scored from 0 to 3, and the scores were added up.
      RESULTS: All subjects completed the study without any complication. The gastric
      emptying rate [T(1/2) (min)] was in normal range (65.6 +/- 12.6 min). Endoscopic
      gastric emptying was correlated significantly with gastric clearance of ROMs (r =
      0.627, p = 0.012). Endoscopic gastric emptying and gastric clearance of ROMs
      after administration of mosapride showed significant differences in the 10 mg
      group (p < 0.05). CONCLUSION: Endoscopy can evaluate gastric emptying safely and
      simply on an outpatient basis. A 10 mg dose of mosapride enhanced gastric
      emptying, assessed by both endoscopy and ROMs.

PMID- 20046512
TI  - Helicobacter pylori urease activity is influenced by ferric uptake regulator.
AB  - PURPOSE: The role of the Ferric Uptake Regulator (FUR) in the acid resistance of
      Helicobacter pylori (H. pylori) has been thought to be independent of urease.
      However, we demonstrated in this study that Fur influences urease activity.
      MATERIALS AND METHODS: A fur knockout mutant of H. pylori was constructed by
      replacing the Fur gene with a kanamycin resistant marker gene. The wild-type H.
      pylori and fur mutant were compared for survival. The integrity of the inner
      membrane of the bacteria was evaluated by confocal microscopy using membrane
      permeant and -impermeant fluorescent DNA probes. Urease activity of intact H.
      pylori was measured between pH 3 and 8. Real time PCR of both strains was
      performed for urease genes including ureI, ureE, ureF, ureG, and ureH. RESULTS:
      The fur deletion affected the survival of H. pylori at pH 4. The urease activity
      curve of the intact fur mutant showed the same shape as the wild-type but was 3
      fold lower than the wild-type at a pH of less than 5. Real time PCR revealed that
      the expression of all genes was consistently down-regulated in the fur mutant.
      CONCLUSION: The results of this study showed that fur appears to be involved in
      acid resistant H. pylori urease activity.

PMID- 20046513
TI  - Increased immunoendocrine cells in intestinal mucosa of postinfectious irritable
      bowel syndrome patients 3 years after acute Shigella infection--an observation in
      a small case control study.
AB  - PURPOSE: Postinfectiously irritable bowel syndrome (PI-IBS) develops in 3-30% of
      individuals with bacterial gastroenteritis. Recent studies demonstrated increases
      in inflammatory components in gut mucosa of PI-IBS patients even after complete
      resolution of infection. We aimed to investigate histological changes in colon
      and rectum of PI-IBS subjects after long term period of infection. MATERIALS AND
      METHODS: We recruited PI-IBS subjects who had been diagnosed IBS after complete
      resolution of enteritis caused by shigellosis outbreak 3 years earlier. We
      compared unmatched four groups, PI-IBS (n = 4), non PI-IBS (n = 7), D-IBS (n = 7,
      diarrhea predominant type) and healthy controls (n = 10). All of them underwent
      colonoscopic biopsy at three areas, including descending colon (DC), sigmoid
      colon (SC) and rectum, which were assessed for 5-hydroxytryptamine (5-HT)/peptide
      YY (PYY)-containing enterochromaffin (EC) cell, intraepithelial (IEL) and lamina
      propria T lymphocyte (CD3), CD8 lymphocytes, mast cells and CD68/calprotectin+
      macrophages. RESULTS: All subjects had no structural or gross abnormalities at
      colonoscopy. In PI-IBS, 5-HT containing EC cells, PYY containing EC cells, IELs,
      CD3 lymphocytes, CD8 lymphocytes, mast cells, and CD68 + macrophages were
      increased compared to control (p < 0.05). In D-IBS, PYY containing EC cells,
      IELs, and CD3 lymphocytes were increased compared to control (p < 0.05). In PI
      IBS, 5-HT containing EC cells tended to increase and PYY containing EC cells, CD8
      lymphocytes, mast cells, and CD68+ macrophages were increased compared to non PI
      IBS (p < 0.05). Calprotectin + marcrophages were decreased in PI-IBS, non PI-IBS
      and IBS compared to control. CONCLUSION: The immunoendocrine cells were
      sporadically increased in PI-IBS, non PI-IBS and D-IBS compared with control. Our
      findings in a very small number of patients suggest that mucosal inflammation may
      play a role in long-term PI-IBS, and that other sub-groups of IBS and larger
      scale studies are needed to confirm this observation.

PMID- 20046514
TI  - Delivery of factor VIII gene into skeletal muscle cells using lentiviral vector.
AB  - PURPOSE: This study was designed to investigate whether transduction of
      lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into
      skeletal muscle could increase circulating hFVIII concentrations. MATERIALS AND
      METHODS: A LV containing bacterial LacZ gene as a control or human FVIII gene was
      intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley
      rats. The plasma human FVIII concentration and neutralizing anti-FVIII antibodies
      were measured for up to 12 weeks in these experimental animals. RESULTS: The
      plasma human FVIII levels in the rats injected with LV carrying FVIII cDNA peaked
      at post-injection 1st week (5.19 +/- 0.14 ng/mL vs. 0.21 +/- 0.05 ng/mL in
      control rats , p < 0.05). Elevated hFVIII concentrations were maintained for 4
      weeks (2.52 +/- 0.83 ng/mL vs. 0.17 +/- 0.08 ng/mL in control rats, p < 0.05)
      after a single intramuscular injection. In the Bethesda assay, neutralizing
      antibodies for FVIII protein were detected only in FVIII-LV injected rats by the
      10th week, but not in control rats. CONCLUSION: This study suggested that a
      single administration of an advanced generation LV carrying the human FVIII cDNA
      resulted in elevation of FVIII level in immune competent rats, and that this gene
      transfer approach to the skeletal muscle could be an effective tool in treatment
      of hemophilia A.

PMID- 20046516
TI  - Therapeutic potential of human adipose stem cells in a rat myocardial infarction
      model.
AB  - PURPOSE: Stem cell transplantation is expected to have good effects in the
      treatment of myocardial infarction (MI). We tested the effect of the
      transplantation of human adipose-derived cells (ASCs) in Sprague-Dawley (SD) rats
      with myocardial infarctions. MATERIALS AND METHODS: ASCs were isolated from the
      waste of elective abdominal surgery. The MI model was set up in SD rats by
      permanent ligation of the left anterior descending coronary artery. One week
      after MI, either 1 x 10(6) ASCs or an equal volume of phosphate-buffered saline
      (PBS) was injected into the infarct zone. Cardiac function was assessed by
      echocardiography, 1 day, 1 week, 2 weeks, and 4 weeks after treatment. Four weeks
      after transplantation, immunohistochemistry was performed. RESULTS: Left
      ventricular function, including fractional shortening (FS), and ejection fraction
      (EF) showed a significant improvement in the ASCs transplantation group compared
      to the PBS group 4 weeks after treatment (p < 0.05). The anterior wall thickness
      of the left ventricle was significantly thicker in the ASCs transplantation group
      compared to the PBS group (p < 0.01). Multiple troponin T staining, and
      irregular, small amounts of connexin 43 expression also was observed in the ASCs
      transplantation group. Infarcted myocardium showed higher capillary density in
      the ASCs transplantation group than in the PBS injected group (p < 0.01).
      CONCLUSION: This study provides encouraging evidence that transplantation of ASCs
      can improve cardiac function of infarct myocardium in rat models with a
      limitation of cardiac remodeling, improved wall thickness, and increased
      neovascularization.

PMID- 20046515
TI  - Long-Term clinical outcomes according to initial management and thrombolysis in
      myocardial infarction risk score in patients with acute non-ST-segment elevation
      myocardial infarction.
AB  - PURPOSE: There is still debate about the timing of revascularization in patients
      with acute non-ST-segment elevation myocardial infarction (NSTEMI). We analyzed
      the long-term clinical outcomes of the timing of revascularization in patients
      with acute NSTEMI obtained from the Korea Acute Myocardial Infarction Registry
      (KAMIR). MATERIALS AND METHODS: 2,845 patients with acute NSTEMI (65.6 +/- 12.5
      years, 1,836 males) who were enrolled in KAMIR were included in the present
      study. The therapeutic strategy of NSTEMI was categorized into early invasive
      (within 48 hours, 65.8 +/- 12.6 years, 856 males) and late invasive treatment
      (65.3 +/- 12.1 years, 979 males). The initial- and long-term clinical outcomes
      were compared between two groups according to the level of Thrombolysis In
      Myocardial Infarction (TIMI) risk score. RESULTS: There were significant
      differences in-hospital mortality and the incidence of major adverse cardiac
      events during one-year clinical follow-up between two groups (2.1% vs. 4.8%, p <
      0.001, 10.0% vs. 13.5%, p = 0.004, respectively). According to the TIMI risk
      score, there was no significant difference of long-term clinical outcomes in
      patients with low to moderate TIMI risk score, but significant difference in
      patients with high TIMI risk score (>or= 5 points). CONCLUSIONS: The old age,
      high Killip class, low ejection fraction, high TIMI risk score, and late invasive
      treatment strategy are the independent predictors for the long-term clinical
      outcomes in patients with NSTEMI.

PMID- 20046517
TI  - Seizure-like activities during head-up tilt test-induced syncope.
AB  - PURPOSE: Some patients with neurally mediated reflex syncope may be misdiagnosed
      as epilepsy because myoclonic jerky movements are observed during syncope. The
      seizure-like activities during the head-up tilt test (HUT) have been rarely
      reported. The purpose of this study was to assess the characteristics of these
      seizure-like activities and evaluate whether there are differences in the
      clinical characteristics and hemodynamic parameters of patients with neurally
      mediated reflex syncope with and without seizure-like activities during HUT
      induced syncope. MATERIALS AND METHODS: The medical records of 1,383 consecutive
      patients with a positive HUT were retrospectively reviewed, and 226 patients were
      included in this study. RESULTS: Of 226 patients, 13 (5.75%) showed seizure-like
      activities, with 5 of these (2.21%) having multifocal myoclonic jerky movements,
      5 (2.21%) having focal seizure-like activity involving one extremity, and 3
      (1.33%) having upward deviation of eye ball. Comparison of patients with and
      without seizure-like activities revealed no significant differences in terms of
      clinical variables and hemodynamic parameters during HUT. CONCLUSION: Seizure
      like activities occurred occasionally during HUT-induced syncope in patients with
      neurally mediated reflex syncope. The seizure-like activities during HUT might
      not be related to the severity of the syncopal episodes or hemodynamic changes
      during HUT.

PMID- 20046518
TI  - Effect of sildenafil on neuropathic pain and hemodynamics in rats.
AB  - PURPOSE: The inhibition of phosphodiesterase 5 produces an antinociception
      through the increase of cyclic guanosine monophosphate (cGMP), and increasing
      cGMP levels enhance the release of gamma-aminobutyric acid (GABA). Furthermore,
      this phosphodiesterase 5 plays a pivotal role in the regulation of the
      vasodilatation associated to cGMP. In this work, we examined the contribution of
      GABA receptors to the effect of sildenafil, a phosphodiesterase 5 inhibitor, in a
      neuropathic pain rat, and assessed the hemodynamic effect of sildenafil in normal
      rats. MATERIALS AND METHODS: Neuropathic pain was induced by ligation of L5/6
      spinal nerves in Sprague-Dawley male rats. After observing the effect of
      intravenous sildenafil on neuropathic pain, GABAA receptor antagonist
      (bicuculline) and GABAB receptor antagonist (saclofen) were administered prior to
      delivery of sildenafil to determine the role of GABA receptors in the activity of
      sildenafil. For hemodynamic measurements, catheters were inserted into the tail
      artery. Mean arterial pressure (MAP) and heart rate (HR) were measured over 60
      min following administration of sildenafil. RESULTS: Intravenous sildenafil dose
      dependently increased the withdrawal threshold to the von Frey filament
      application in the ligated paw. Intravenous bicuculline and saclofen reversed the
      antinociception of sildenafil. Intravenous sildenafil increased the magnitude of
      MAP reduction at the maximal dosage, but it did not affect HR response.
      CONCLUSION: These results suggest that sildenafil is active in causing
      neuropathic pain. Both GABAA and GABAB receptors are involved in the
      antinociceptive effect of sildenafil. Additionally, intravenous sildenafil
      reduces MAP without affecting HR.

PMID- 20046519
TI  - Comparison of azasetron and ondansetron for preventing postoperative nausea and
      vomiting in patients undergoing gynecological laparoscopic surgery.
AB  - PURPOSE: We compared the prophylactic effects of intravenously administered
      azasetron (10 mg) and ondansetron (8 mg) on postoperative nausea and vomiting
      (PONV) in patients undergoing gynecological laparoscopic surgery under general
      anesthesia. MATERIALS AND METHODS: We studied 98 ASA physical status I or II 20
      65 years old, female patients, in this prospective, randomized, double blind
      study. Patients were randomly divided into two groups and received ondansetron 8
      mg (group O) or azasetron 10 mg (group A) 5 min before the end of surgery. The
      incidence of PONV, Visual Analogue Scale (VAS) for pain, need for rescue
      antiemetic and analgesics, and adverse effects were checked at 1, 6, 12, 24, and
      48 h postoperatively. RESULTS: The overall incidence of PONV was 65% in group O
      and 49% in group A. The incidence of PONV was significantly higher in group O
      than in group A at 12-24 h postoperatively (nausea; 24% vs. 45%, p = 0.035,
      vomiting; 2% vs. 18%, p = 0.008), but there were no significant differences at 0
      1, 1-6, 6-12 or 24-48 h. CONCLUSION: In conclusion, azasetron (10 mg) produced
      same incidence of PONV as ondansetron (8 mg) in patients undergoing general
      anesthesia for gynecological laparoscopic surgery. Azasetron was more effective,
      in the intermediate post-operative period, between 12 and 24 h.

PMID- 20046520
TI  - High dose three-dimensional conformal boost using the real-time tumor tracking
      radiotherapy system in cervical cancer patients unable to receive intracavitary
      brachytherapy.
AB  - PURPOSE: The purpose of this study is to evaluate the clinical results of
      treatment with a high dose of 3-dimensional conformal boost (3DCB) using a real
      time tracking radiation therapy (RTRT) system in cervical cancer patients.
      MATERIALS AND METHODS: Between January 2001 and December 2004, 10 patients with
      cervical cancer were treated with a high dose 3DCB using RTRT system. Nine
      patients received whole pelvis radiation therapy (RT) with a median dose of 50 Gy
      (range, 40-50 Gy) before the 3DCB. The median dose of the 3DCB was 30 Gy (range,
      25-30 Gy). Eight patients received the 3DCB twice a week with a daily fraction of
      5 Gy. The determined endpoints were tumor response, overall survival, local
      failure free survival, and distant metastasis free survival. The duration of
      survival was calculated from the time of the start of radiotherapy. RESULTS: All
      patients were alive at the time of analysis and the median follow-up was 17.6
      months (range, 4.9-27.3 months). Complete response was achieved in nine patients
      and one patient had a partial response. The 1- and 2-year local failure free
      survival was 78.8% and 54%, respectively. The 1- and 2-year distant metastasis
      free survival was 90% and 72%, respectively. Late toxicity of a grade 2 rectal
      hemorrhage was seen in one patient. A subcutaneous abscess was encountered in one
      patient. CONCLUSION: The use of the high dose 3DCB in the treatment of cervical
      cancer is safe and feasible where intracavitary brachytherapy (ICBT) is unable to
      be performed. The escalation of the 3DCB dose is currently under evaluation.

PMID- 20046521
TI  - Long-term results of total hip arthroplasty with an extensively porous coated
      stem in patients younger than 45 years old.
AB  - PURPOSE: This study analyzed the long-term results of cementless total hip
      arthroplasty using an extensively porous coated stem in patients younger than 45
      years old. MATERIALS AND METHODS: The clinical and radiographic results of 45
      hips from 38 patients who underwent cementless total hip replacement arthroplasty
      with an AML prosthesis were reviewed retrospectively. The average follow-up was
      12 years (range, 10-15 years). RESULTS: The average Harris hip score at the time
      of final follow-up was 87.3 (range 77-94) points. Forty two hips (93.3%) showed
      excellent and good clinical results. Osteolysis occurred around the stem in 20
      hips (44.4%) and around the cup in 26 hips (57.8%). Stress-mediated femoral
      resorption was observed in 33 hips (73.3%) at 10 years. There was no incidence of
      resorption progressing after 5 years postoperatively. There was no stem
      loosening. Five hips were revised for osteolysis, cup loosening and polyethylene
      wear. CONCLUSION: The long term results of total hip arthroplasty using an
      extensively porous coated stem were acceptable, and there was no case involving
      the progression of proximal bone resorption.

PMID- 20046522
TI  - Comparisons of three automated systems for genomic DNA extraction in a clinical
      diagnostic laboratory.
AB  - PURPOSE: The extraction of nucleic acid is initially a limiting step for
      successful molecular-based diagnostic workup. This study aims to compare the
      effectiveness of three automated DNA extraction systems for clinical laboratory
      use. MATERIALS AND METHODS: Venous blood samples from 22 healthy volunteers were
      analyzed using QIAamp Blood Mini Kit (Qiagen), MagNA Pure LC Nucleic Acid
      Isolation Kit I (Roche), and Magtration-Magnazorb DNA common kit-200N (PSS). The
      concentration of extracted DNAs was measured by NanoDrop ND-1000 (PeqLab). Also,
      extracted DNAs were confirmed by applying in direct agarose gel electrophoresis
      and were amplified by polymerase chain reaction (PCR) for human beta-globin gene.
      RESULTS: The corrected concentrations of extracted DNAs were 25.42 +/- 8.82
      ng/microL (13.49-52.85 ng/microL) by QIAamp Blood Mini Kit (Qiagen), and 22.65 +/
      14.49 ng/microL (19.18-93.39 ng/microL) by MagNA Pure LC Nucleic Acid Isolation
      Kit I, and 22.35 +/- 6.47 ng/microL (12.57-35.08 ng/microL) by Magtration
      Magnazorb DNA common kit-200N (PSS). No statistically significant difference was
      noticed among the three commercial kits (p > 0.05). Only the mean value of DNA
      purity through PSS was slightly lower than others. All the extracted DNAs were
      successfully identified in direct agarose gel electrophoresis. And all the
      product of beta-globin gene PCR showed a reproducible pattern of bands.
      CONCLUSION: The effectiveness of the three automated extraction systems is of an
      equivalent level and good enough to produce reasonable results. Each laboratory
      could select the automated system according to its clinical and laboratory
      conditions.

PMID- 20046523
TI  - In-vitro efficacy of synergistic antibiotic combinations in multidrug resistant
      Pseudomonas aeruginosa strains.
AB  - PURPOSE: Combination antibiotic treatment is preferred in nosocomial infections
      caused by Pseudomonas aeruginosa (P. aeruginosa). In vitro synergism tests were
      used to choose the combinations which might be used in clinic. The aim of this
      study was to investigate the synergistic efficacy of synergistic antibiotic
      combinations in multidrug resistant P. aeruginosa strains. MATERIALS AND METHODS:
      Synergistic efficacies of ceftazidime-tobramycin, piperacillin/tazobactam
      tobramycin, imipenem-tobramycin, imipenem-isepamycin, imipenem-ciprofloxacin and
      ciprofloxacin-tobramycin combinations were investigated by checkerboard technique
      in 12 multiple-resistant and 13 susceptible P. aeruginosa strains. RESULTS: The
      ratios of synergy were observed in ceftazidime-tobramycin and
      piperacillin/tazobactam-tobramycin combinations as 67%, and 50%, respectively, in
      resistant strains, whereas synergy was not detected in other combinations. The
      ratios of synergy were observed in ceftazidime-tobramycin,
      piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-ciprofloxacin
      and imipenem-isepamycin combinations as 31%, 46%, 15%, 8%, 8%, and respectively,
      in susceptible strains, whereas synergy was not detected in ciprofloxacin
      tobramycin combination. Antagonism was not observed in any of the combinations.
      CONCLUSION: Although the synergistic ratios were high in combinations with
      ceftazidime or piperacillin/tazobactam and tobramycin, the concentrations in
      these combinations could not usually reach clinically available levels. Thus, the
      solution of the problems caused by multiple resistant P. aeruginosa should be
      based on the prevention of the development of resistance and spread of the
      causative agent between patients.

PMID- 20046524
TI  - The prismatic effect on stereoacuity in intermittent exotropia.
AB  - PURPOSE: To evaluate the effect of acrylic refractive prism and Fresnel membrane
      prism on stereoacuity in intermittent exotropia. MATERIALS AND METHODS:
      Stereoacuities of fifty-two patients (mean age, 12.4 years; range 6 to 45 years)
      with intermittent exotropia were measured using the Titmus and TNO stereotests,
      while they wore prisms of varying power on nonfixating eye or evenly on each eye.
      RESULTS: Stereoacuities were significantly reduced with increasing prism power
      for both prisms, ranging from 8 to 25 prism dipotres. The effects on stereoacuity
      in single acrylic prism and single Fresnel prism were similar, whereas spilt
      Fresnel prisms reduced stereoacuity more than spilt acrylic prisms. Spilt prisms
      were found to have much less effect on stereoacuity than single prisms for both
      acrylic and Fresnel prisms. CONCLUSION: The use of acrylic refractive prism
      shared evenly on each eye would be optimal method to minimize the reduction of
      stereoacuity during the prismatic therapy for intermittent exotropia.

PMID- 20046525
TI  - Evaluation of three different methods to establish animal models of Acanthamoeba
      keratitis.
AB  - PURPOSE: To produce animal models of Acanthamoeba keratitis and to evaluate the
      advantages and adaptation range of each of the three methods employed. MATERIALS
      AND METHODS: Mice and Wistar rats in three groups of 15 rats and 15 mice each
      were used to establish the models. Right corneas in group A were scratched and
      challenged with Acanthamoeba. Those in group B were scratched and covered with
      contact lenses incubated with Acanthamoeba. Those in group C received an
      intrastromal injection of Acanthamoeba. Five rats and 5 mice in each group were
      used for histopathological investigations and the other 10 in each group were
      used for clinical evaluation. The models were evaluated by slit lamp examination,
      microscopic examination and culture of corneal scrapings, HE staining of corneal
      sections, and pathological scoring of the infections. RESULTS: Four rats and 6
      mice in group A, 7 rats and 8 mice in group B, and 10 rats and 10 mice in group C
      developed typical Acanthamoeba keratitis. CONCLUSION: Corneal scratching alone
      has the lowest infection rate, while scratching and then covering with
      contaminated contact lenses has a moderate rate of infection and most closely
      mimics what happens in most human infections. Intrastromal injection of
      Acanthamoeba gives a much higher infection rate and more severe Acanthamoeba
      keratitis.

PMID- 20046526
TI  - A case of neck abscess caused by Salmonella serotype D in a patient with liver
      cirrhosis.
AB  - Non-typhoidal salmonellosis, which is increasing nowadays in Korea as well as in
      the developed countries, is manifested as enteritis in most cases, but it also
      encompasses bacteremia, intraabdominal infections, and bone, joint and soft
      tissue infections. These rare diseases are known to result from primary
      gastrointestinal infection and subsequent bacteremia with or without symptoms. We
      experienced a case of neck abscess caused by Salmonella serotype D, which is a
      rare but important differential diagnosis of neck abscess. We herein report it.

PMID- 20046527
TI  - Cerebellar nocardiosis and myopathy from long-term corticosteroids for idiopathic
      thrombocytopenia.
AB  - Infection of the central nervous system with Nocardia sp. usually manifests as
      supratentorial abscesses. Supratentorial and cerebellar abscesses from infection
      with Nocardia sp. following immunosuppression with long-term corticosteroids for
      idiopathic thrombocytopenia (ITP) have not been reported. An 83 years-old, human
      immunodeficiency virus (HIV)-negative, polymorbid male with ITP for which he
      required corticosteroids since age 53 years developed tiredness, dyspnoea,
      hemoptysis, abdominal pain, and progressive gait disturbance. Imaging studies of
      the lung revealed an enhancing tumour in the right upper lobe with central and
      peripheral necrosis, multiple irregularly contoured hyperdensities over both
      lungs, and right-sided pleural effusions. Sputum culture grew Nocardia sp.
      Neurological diagnostic work-up revealed dysarthria, dysphagia, ptosis,
      hypoacusis, tremor, dysdiadochokinesia, proximal weakness of the lower limbs,
      diffuse wasting, and stocking-type sensory disturbances. The neurological
      deficits were attributed to an abscess in the upper cerebellar vermis, myopathy
      from corticosteroids, and polyneuropathy. Meropenem for 37 days and trimethoprime
      sulfamethoxazole for 3 months resulted in a reduction of the pulmonary, but not
      the cerebral lesions. Therefore, sultamicillin was begun, but without success.
      Long-term therapy with corticosteroids for ITP may induce not only steroid
      myopathy but also immune-incompetence with the development of pulmonary and
      cerebral nocardiosis. Cerebral nocardiosis may not sufficiently respond to long
      term antibiotic therapy why switching to alternative antibiotics or surgery may
      be necessary.

PMID- 20046528
TI  - A case of pathologic splenic rupture as the initial manifestation of acute
      myeloid leukemia M2.
AB  - A pathologic splenic rupture refers to a rupture without trauma. A splenic
      rupture as the initial manifestation of acute myeloid leukemia is extremely rare.
      In this study, we described a rare case of acute myeloid leukemia presenting
      principally as an acute abdomen due to a pathologic splenic rupture in a 35-year
      old male patient. We can assert that a pathologic splenic rupture in hematologic
      diseases is a potentially life-threatening complication, which necessitates
      immediate operative intervention. Any such patient complaining about left upper
      abdominal tenderness should be closely observed, and further diagnostic
      investigations (ultrasonograph of the abdomen, abdominal CT scan) should be
      initiated in order to rule out a splenic rupture. The oncologist should be aware
      of this rare initial presentation of acute myeloid leukemia (AML) M2, as the
      condition generally necessitates a prompt splenectomy.

PMID- 20046529
TI  - Sequential bilateral lung resection in a patient with Mycobacterium abscessus
      lung disease refractory to medical treatment.
AB  - Mycobacterium abscessus (M. abscessus) is the second most common nontuberculous
      mycobacteria (NTM) in South Korea. Nevertheless, the diagnosis and treatment of
      M. abscessus lung disease can be problematic. Surgical resection has been tried
      for patients with localized M. abscessus lung disease refractory to medical
      treatment. Here, we report on a 25-year-old woman with M. abscessus lung disease
      who had been diagnosed and treated three times for pulmonary tuberculosis. She
      was initially diagnosed as having M. intracellulare lung disease; however, M.
      abscessus was isolated after several months of medication. She had multiple
      bronchiectatic and cavitary lesions bilaterally, and M. abscessus was repeatedly
      isolated from her sputa despite prolonged treatment with clarithromycin,
      ethambutol, moxifloxacin, and amikacin. She improved only after sequential
      bilateral lung resection. Based on the experience with this patient, we suggest
      that, if medical treatment fails, surgical resection of a diseased lung should be
      considered even in patients with bilateral lesions.

PMID- 20046530
TI  - Eosinophilic gastroenteritis with eosinophilic dermatitis.
AB  - Eosinophilic gastroenteritis (EG) is characterized by eosinophilic infiltration
      of the bowel wall and variable gastrointestinal manifestations. Clinicians should
      have a high index of suspicion for EG when faced with gastrointestinal symptoms
      and peripheral eosinophilia to avoid incorrect diagnosis and inappropriate
      treatments. A 24-year-old woman was admitted to our hospital complaining of acute
      right lower quadrant abdominal pain and a laparoscopic appendectomy performed for
      a presumed diagnosis of an acute appendicitis. However, the procedure revealed
      bowel edema and a moderate amount of ascites without evidence of a suppurative
      appendicitis. Postoperatively, she showed persistent and progressive
      eosinophilia, exudative eosinophilic ascites, eosinophilic infiltration of the
      resected appendix wall, and eosinophilic infiltration of gastroduodenal mucosa. A
      punch biopsy of the abdominal skin also revealed inflammation with marked
      eosinophilic infiltration of the skin. She recovered after the treatment with a
      low dose of steroid for the EG with eosinophilic dermatitis. EG with eosinophilic
      dermatitis has not been reported yet and is considered fortuitous in this case.

PMID- 20046531
TI  - A unique instrumental malfunction during robotic prostatectomy.
AB  - Over the past decade, the introduction of robotics in the field of medicine has
      provided a new approach to patients requiring surgery, and both its advantages
      and disadvantages are currently under study by many groups worldwide. The use of
      robotics has especially been considered by the urological community as a
      treatment option in radical prostatectomy. The current case report is one in
      which the da Vinci Surgical System, with fourth arm use was employed in radical
      prostatectomy. This case presents a unique occurrence in which a bolt of the
      Prograsper forcep became loose during an operation, leading to diminished device
      functionality and later impedance of its removal. A circumstance such as this has
      not previously been reported, so we introduce for other robotic surgeons our
      unique instrumental malfunction case during a robotic prostatectomy.

PMID- 20046532
TI  - An overview of observational sleep research with application to sleep stage
      transitioning.

PMID- 20046533
TI  - Prevalence and Correlates of Childhood-Onset Anxiety Disorders among Latinos and
      Non-Latino Whites in the United States.
AB  - Anxiety disorders are the most prevalent class of psychiatric disorders (Kessler,
      et al., 2005) and their early onset places individuals at risk for a wide range
      of subsequent problems (Weissman, et al., 1999). Data from the National Latino
      and Asian American Study (NLAAS) and the National Comorbidity Survey-Replication
      (NCS-R) were used to investigate the prevalence and correlates of childhood-onset
      anxiety disorders among U.S.-born whites, U.S.-born Latinos, and foreign-born
      Latinos. Significant differences in rates of childhood-onset anxiety disorders
      were found, with foreign-born Latinos reporting the lowest rates. Across all
      three ethnicity/nativity groups, individuals with childhood-onset anxiety
      disorders had equal or higher levels of past-year impairment, relative to
      individuals with adult-onset anxiety disorders. The chronic course associated
      with childhood-onset anxiety disorders was also revealed to be present regardless
      of ethnicity and nativity, as indicated by the similarities across groups in the
      mean number of lifetime disorders and comorbidity rates. Treatment and assessment
      recommendations are discussed with respect to the findings.

PMID- 20046534
TI  - Emotional Reactions During and After Trauma: A Comparison of Trauma Types.
AB  - Peri- and posttraumatic emotional responses have been understudied, and
      furthermore, have rarely been compared among trauma types. The current study
      compared college students' retrospective self-reports of peri- and posttraumatic
      responses of fear, shame, guilt, anger, and sadness among four types of traumatic
      events: sexual assault, physical assault, transportation accident, and
      illness/injury. Overall emotional responding was generally high for all trauma
      types, and for those in the sexual assault group, emotion increased sharply from
      the peri- to posttraumatic time-point. Generally, fear was higher during the
      trauma compared to after the trauma, whereas the other emotions tended to remain
      stable or increase posttrauma. The sexual assault group tended to report higher
      levels of posttrauma emotion than the other trauma type groups.

PMID- 20046535
TI  - A Preliminary Examination of Thought Suppression, Emotion Regulation, and Coping
      in a Trauma Exposed Sample.
AB  - Attempts to modulate negative emotional and cognitive symptoms of Posttraumatic
      Stress Disorder (PTSD) may be related to psychopathology. Trauma exposed
      undergraduates, 31 reporting severe PTSD symptoms (PTSD group) and 34 without
      PTSD symptoms (no-PTSD group), completed measures of PTSD, depression, anxiety,
      thought control, emotion regulation, and coping. The PTSD group had greater
      psychopathology and overall modulation strategy use than the no-PTSD group.
      Thought suppression, emotion suppression, and avoidant coping strategies were
      positively related to psychopathology, whereas emotion reappraisal and approach
      coping strategies were either not related or weakly negatively related.
      Hierarchical multiple regressions with psychopathologic variables as criteria and
      modulation strategies as predictors indicated significant models in all cases.
      Generally, thought suppression was the only significant independent predictor of
      psychopathology.

PMID- 20046536
TI  - FAST DISPLACEMENT PROBABILITY PROFILE APPROXIMATION FROM HARDI USING 4TH-ORDER
      TENSORS.
AB  - Cartesian tensor basis have been widely used to approximate spherical functions.
      In Medical Imaging, tensors of various orders have been used to model the
      diffusivity function in Diffusion-weighted MRI data sets. However, it is known
      that the peaks of the diffusivity do not correspond to orientations of the
      underlying fibers and hence the displacement probability profiles should be
      employed instead. In this paper, we present a novel representation of the
      probability profile by a 4(th) order tensor, which is a smooth spherical function
      that can approximate single-fibers as well as multiple-fiber structures. We also
      present a method for efficiently estimating the unknown tensor coefficients of
      the probability profile directly from a given high-angular resolution diffusion
      weighted (HARDI) data set. The accuracy of our model is validated by experiments
      on synthetic and real HARDI datasets from a fixed rat spinal cord.

PMID- 20046538
TI  - SCREENING, BRIEF INTERVENTION AND REFERRAL TO TREATMENT (SBIRT) IN A POLISH
      EMERGENCY ROOM: CHALLENGES IN CULTURAL TRANSLATION OF SBIRT.
AB  - A randomized clinical controlled trial of screening, brief intervention and
      referral to treatment (SBIRT) for drinking and related problems among at-risk and
      dependent drinkers, using nurse interventionists, was undertaken in an emergency
      room (ER) in Sosnowiec, Poland, the first level-one trauma center in that
      country. This study was the first outside of the U.S. to test protocols developed
      in a 14-site collaborative SBIRT study. Because Poland has both a pattern of
      heavy drinking and a highly accessible specialized alcohol treatment system, it
      offered a key setting for cultural translation of SBIRT to the international
      context of a new and emerging health care system. It also offered the opportunity
      to test the effectiveness of SBIRT with both at-risk and dependent drinkers, and
      to test the feasibility of using ER nursing staff to provide the brief
      intervention, serving as a potential model for ongoing implementation of SBIRT in
      ER settings. Findings suggest that the U.S.-based SBIRT protocols can be
      successfully translated to other cultures, and that nurses can be successfully
      trained to provide brief intervention for problem drinking in the ER setting.

PMID- 20046539
TI  - Finding Occurrences of Relevant Functional Elements in Genomic Signatures.
AB  - For genomic applications, signature-finding algorithms identify over-represented
      signatures (words) in collections of DNA sequences. The results can be presented
      as a specific sequence of bases, a consensus sequence showing possible
      combination of bases, or a matrix of weighted possibilities at each position.
      These results are often compared to a biological set of binding sites (i.e.,
      known functional elements), which are usually represented as weighted matrices.
      The comparison is made by scoring the signatures against each weight matrix to
      identify the best option for a positive hit. However, this approach can
      misclassify results when applied to short sequences, which are a frequent result
      of signature finders. We describe a novel method using a window around the
      original sequences (those which the signature is based upon) to improve the
      comparison and identify a more significant measure of similarity. In doing so,
      our method transforms a list of DNA signatures into a resource of characterized
      binding sites with known functional roles and identifies novel elements in need
      of further elucidation.

PMID- 20046540
TI  - Sildenafil- and tadalafil-associated optic neuropathy: implications for men after
      prostate cancer treatment.

PMID- 20046541
TI  - PUMA Kills Stem Cells to Stall Cancer?
AB  - Apoptosis evasion is a hallmark of human cancer. PUMA is a BH3-only Bcl-2 family
      protein that mediates both p53-dependent and independent apoptosis. However, its
      role in tumor suppression had not been well established. Our recent work provides
      direct evidence that PUMA plays an important role in suppressing intestinal
      tumorigenesis in two mouse models including (i) the azoxymethane (AOM)/dextran
      sulfate sodium salt (DSS)-treated mice and (ii) APC(Min/+) mice. The activities
      of PUMA appeared to be in the intestinal stem cells, and involve both p53
      dependent response to DNA damage, and p53-independent mechanisms triggered by
      inflammation. Our data suggest that the interplay between different apoptotic
      pathways in intestinal stem cells underlie the initiation of intestinal
      carcinogenesis, and should be considered in the context of cancer prevention and
      therapy.

PMID- 20046542
TI  - An Interaction Based Composable Architecture for Building Scalable Models of
      Large Social, Biological, Information and Technical Systems.

PMID- 20046544
TI  - Cumulative Risk and Continuity in Nonparental Care from Infancy to Early
      Adolescence.
AB  - Variations in amounts of nonparental care across infancy, preschool, early
      elementary school, and early adolescence were examined in a longitudinal sample
      (N = 438). Of interest was (a) continuity in use of the different arrangements,
      (b) whether the arrangements were additively and cumulatively associated with
      children's externalizing behavior problems, and (c) whether predictive relations
      were accounted for by social-ecological (socioeconomic status, mothers'
      employment status, marital status) and social-experiential (parenting quality,
      exposure to aggressive peers) factors. Correlations among overall amounts of care
      provided little evidence of cross-time continuity. Consistent with the cumulative
      risk perspective, Grade 1 self-care and Grade 6 unsupervised peer contact
      incrementally predicted Grade 6 externalizing problems. Most of the predictive
      associations were accounted for by family background and social relationship
      factors.

PMID- 20046543
TI  - Formaldehyde-assisted isolation of regulatory elements.
AB  - Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) is based on locus
      specific variations in the ability of protein components of chromatin to trap
      genomic DNA following formaldehyde treatment. This variation is mostly due to
      uneven nucleosome distribution since histones are the most abundant and highly
      crosslinkable components of chromatin. The method can identify and enrich for
      physically accessible DNA segments of the eukaryotic genome corresponding to
      known regulatory regions and regions that might have thus far unidentified
      structural role in the nuclear organization of chromatin. The enrichment patterns
      are cell type specific and thus might provide information about how
      transcriptional systems are organized and regulated in various tissues and how
      they might be disrupted in disease states. Analysis of a 268 kb region of
      chromosome 19 in human fibroblasts shown here demonstrates that while most DNA
      fragments detected by FAIRE correspond to sites of DNaseI hypersensitivity in
      active regions of chromatin, some are found in otherwise repressed chromatin
      domains and at other sites that are not found with other methods used to probe
      chromatin structure. Further exploration of FAIRE is warrented due to the
      simplicity of the protocol and recent advancements in massively parallel
      sequencing.

PMID- 20046545
TI  - Neonatal Physiological Regulation is Associated With Perinatal Factors: A Study
      of Neonates Born to Healthy African American Women Living In Poverty.
AB  - Maternal mental health and prenatal stress are linked with neurobehavioral
      differences in the offspring. The majority of studies documenting this effect
      have been conducted using either predominantly European American infants or
      minority infants exposed to teratogens in utero. In this study, we focus on
      healthy African American women from low-income environments to investigate the
      earliest individual differences in biobehavioral regulation, including resting
      heart rate and variability (HRV). In 87 neonates, HRV was significantly lower in
      those born to mothers reporting past major depressive disorder (p = .01). The
      number of maternal life stressors also was associated with lower neonatal HRV (p
      = .03). Obstetrical complications were not associated with significant
      differences, but breast- versus bottle-feeding in the first few days of life was
      related to higher HRV (p = .04). Early variation in physiological regulation may
      be linked to subsequent individual differences in response to stress. Thus,
      identifying the earliest point in development when such differences can be
      reliably measured may result in opportunities for prevention of later deficits in
      regulating response to stress.

PMID- 20046546
TI  - Climatic Warmth and National Wealth: Some Culture-Level Determinants of National
      Character Stereotypes.
AB  - National character stereotypes are widely shared, but do not reflect assessed
      levels of personality traits. In this article we present data illustrating the
      divergence of stereotypes and assessed personality traits in north and south
      Italy, test hypotheses about the associations of temperature and national wealth
      with national character stereotypes in 49 cultures, and explore possible links to
      national values and beliefs. Results suggest that warmth and wealth are common
      determinants of national stereotypes, but that there are also idiosyncratic
      influences on the perceptions of individual nations.

PMID- 20046547
TI  - Sub-group Classification of Low Back Related Leg Pain: Is this the Catalyst
      Needed for Other Challenging Conditions?

PMID- 20046548
TI  - Interaction between Trigger Points and Joint Hypomobility: A Clinical
      Perspective.
AB  - The relationship between muscle trigger points (TrPs) and joint hypomobility is
      frequently recognized by clinicians. Among different manual therapies aimed at
      inactivating muscle TrPs, ischemic compression and spinal manipulation have shown
      moderately strong evidence for immediate pain relief. Reduction of joint mobility
      appears related to local muscles innervated from the segment, which suggests that
      muscle and joint impairments may be indivisible and related disorders in pain
      patients. Two clinical studies have investigated the relationship between the
      presence of muscle TrPs and joint hypomobility in patients with neck pain. Both
      studies reported that all patients exhibited segmental hypo-mobility at C3-C4
      zygapophyseal joint and TrPs in the upper trapezius, sternocleidomastoid, or
      levator scapulae muscles. There are several theories that have discussed the
      relationship between TrP and joint hypomobility. First, increased tension of the
      taut muscular bands associated with a TrP and facilitation of motor activity can
      maintain displacement stress on the joint. Alternatively, it may be that the
      abnormal sensory input from the joint hypomobility may reflexively activate TrPs.
      It is also conceivable that TrPs provide a nociceptive barrage to the dorsal horn
      neurons and facilitate joint hypomobility. There is scientific evidence showing
      change in muscle sensitivity in muscle TrP after spinal manipulation, which
      suggests that clinicians should include treatment of joint hypomobility in the
      management of TrPs. Nevertheless, the order in which these muscle and joint
      impairments should be treated is not known and requires further investigation.

PMID- 20046549
TI  - Manual correction of an acute lumbar lateral shift: maintenance of correction and
      rehabilitation: a case report with video.
AB  - The acute onset lumbar lateral shift, otherwise known as a list or acute
      scoliosis, is a common clinical observation associated with low back pain. In
      general orthopaedics, the presence of a lateral shift is associated with a poor
      prognosis; however, a manual correction method devised by McKenzie is claimed to
      produce rapid reversal of the deformity and reduction in pain. This single-case
      report presents the details of the McKenzie Mechanical Diagnosis and Treatment
      (MDT) management of a major right-sided lateral shift, which includes the manual
      correction technique, self-correction and management, prophylaxis, pain ablation,
      and rehabilitation to a high level of athletic function, with long-term follow-up
      at 9 months. The lateral shift is widely accepted as being associated with disc
      pathology, but the exact mechanism of shift production remains speculative.
      hypotheses include muscle spasm, avoidance of irritation of a spinal nerve, and
      space-occupying or space-deficient disc mechanics. The hypotheses used to explain
      the lateral shift phenomena are discussed. (Case report is supplemented by video
      stream, available at jmmtonline.com/).

PMID- 20046550
TI  - Changes in Psychological Parameters in Patients with Tension-type Headache
      Following Massage Therapy: A Pilot Study.
AB  - Investigations into complementary and alternative medicine (CAM) approaches to
      address stress, depression, and anxiety of those experiencing chronic pain are
      rare. The objective of this pilot study was to assess the value of a structured
      massage therapy program, with a focus on myofascial trigger points, on
      psychological measures associated with tension-type headache. Participants were
      enrolled in an open-label trial using a baseline control with four 3-week phases:
      baseline, massage (two 3-week periods) and a follow-up phase. Eighteen subjects
      with episodic or chronic tension-type headache were enrolled and evaluated at 3
      week intervals using the State-Trait Anxiety Inventory, Beck Depression
      Inventory, and the Perceived Stress Scale. The Daily Stress Inventory was
      administered over 7-day periods during baseline and the final week of massage.
      Twice weekly, 45-minute massage therapy sessions commenced following the baseline
      phase and continued for 6 weeks. A significant improvement in all psychological
      measures was detected over the timeframe of the study. Post hoc evaluation
      indicated improvement over baseline for depression and trait anxiety following 6
      weeks of massage, but not 3 weeks. A reduction in the number of events deemed
      stressful as well as their respective impact was detected. This pilot study
      provides evidence for reduction of affective distress in a chronic pain
      population, suggesting the need for more rigorously controlled studies using
      massage therapy to address psychological measures associated with TTH.

PMID- 20046551
TI  - Applying Joint Mobilization at Different Cervical Vertebral Levels does not
      Influence Immediate Pain Reduction in Patients with Chronic Neck Pain: A
      Randomized Clinical Trial.
AB  - The aim of the present study was to compare the effects of applying joint
      mobilization at symptomatic and asymptomatic cervical levels in patients with
      chronic nonspecific neck pain. Forty-eight patients aged between 18 and 65 years
      and presenting nonspecific neck pain with a minimum duration of 3 months were
      recruited for the study. Included patients were randomized to one of two
      treatment groups: (i) control group: the most symptomatic vertebral level was
      mobilized; (ii) experimental group: a randomly selected vertebral level was
      chosen and mobilized. All patients received one treatment session. Pain intensity
      in resting position during the most painful active cervical movement as well as
      during vertebral palpation was quantified using an 11-point pain scale. Follow-up
      measures were taken immediately after intervention by a blinded assessor. The
      results showed no significant difference in pain intensity immediately after
      treatment between groups (symptomatic level treated vs. randomly chosen cervical
      vertebral level treated) during resting position, painful active movement, or
      vertebral palpation. Within-group comparisons showed significant pain relief
      after treatment during the most painful active movement as well as during
      vertebral palpation for both groups, but not during resting position. Significant
      change in immediate pain intensity during painful active movement and vertebral
      palpation was achieved after vertebral mobilization. however, both groups
      presented similar pain reductions suggesting that pain reduction due to joint
      mobilization is not specific to the vertebral level being mobilized.

PMID- 20046552
TI  - The effect of an analgesic mobilization technique when applied at symptomatic or
      asymptomatic levels of the cervical spine in subjects with neck pain: a
      randomized controlled trial.
AB  - The purpose of this single-blinded, randomized controlled trial was to compare
      the effects of a manual treatment technique on neck pain and movement sensation
      when applied in different segments of the cervical spine. Consecutive patients
      with neck pain (n=126) were recruited and randomly allocated to two groups (A or
      B). Group A received a single 4-minute pain-alleviating traction at the most
      symptomatic zygopophyseal joint of the cervical segment, where movement was
      correlated with pain. Group B received the same treatment 3 segments away from
      the concordant segment. Pain intensity and sensation of movement were assessed
      with a numeric rating scale (NRS). Statistical analysis included a t-test for
      paired and unpaired samples. Pre- and post-test findings demonstrated significant
      improvements in both types of mobilization although there was no significant
      difference between the two groups. Similar results have been reported in the
      literature for cervical manipulation. The findings of this study question the
      necessity of precise symptom localization tests for a pain treatment. however,
      limitations of the study prevent generalization of these results.

PMID- 20046553
TI  - Interrater reliability of a new classification system for patients with neural
      low back-related leg pain.
AB  - The aim of this study was to investigate the reliability of a new classification
      system for low back-related leg pain arising from neural tissue dysfunction. Leg
      pain is a frequent accompaniment to back pain and is an indicator of the severity
      and prognosis of the disorder. For optimal patient care, treatment should be
      directed according to the identified pathophysiological mechanisms. The authors
      have proposed a sub-classification of neural low back-related leg pain into four
      categories, each requiring a different management strategy: Central Sensitization
      (CS), comprising major features of sensitization of the somatosensory system;
      Denervation (D), arising from significant axonal compromise without evidence of
      major central nervous system changes; Peripheral Nerve Sensitization (PNS),
      arising from nerve trunk inflammation without clinical evidence of significant
      denervation; and Musculoskeletal pain (M), referred from non-neural structures
      such as the disc or facet joints. The purpose of this study was to investigate
      the interrater reliability of this classification system. Forty consecutive
      patients with unilateral low back-related leg pain were independently assessed by
      five pairs of examiners using a physical examination protocol, screening for
      central sensitization of the somatosensory system, neurological deficit, and
      nerve tissue mechano-sensitization. Subjects were classified as follows: CS 30%,
      D 27.5%, PNS 10%, and M 32.5%. Interrater reliability was good with 80% agreement
      and a k of 0.72 (95% Confidence Interval (CI) .57-.86). The findings of the study
      demonstrate that patients with low back-related leg pain can be reliably
      classified to one of the four proposed groups.

PMID- 20046554
TI  - Classification of low back-related leg pain: do subgroups differ in disability
      and psychosocial factors?
AB  - It has been proposed that patients with low back-related leg pain can be
      classified according to pain mechanisms into four distinct subgroups: Central
      Sensitization (CS), Denervation (D), Peripheral Nerve Sensitization (PNS), and
      Musculoskeletal (M). The purpose of this study was to determine whether there
      were any differences in terms of disability and psychosocial factors between
      these four subgroups. Forty-five subjects with low back-related leg pain
      completed the Oswestry Disability Index, the hospital Anxiety and Depression
      Scale, and the Fear Avoidance Beliefs Questionnaire. Subsequently, an examiner
      blinded to the questionnaire results classified the subjects into one of the four
      subgroups, according to the findings of the self-administered Leeds Assessment of
      Neuropathic Signs and Symptoms questionnaire and a physical examination. It was
      found that the PNS subgroup had significantly greater disability compared to all
      other subgroups and significantly greater fear avoidance beliefs about physical
      activity compared to the CS and D subgroups. This highlights the importance of
      sub-classification but also the need to take into account disability and
      psychosocial factors in the management of low back-related leg pain.

PMID- 20046555
TI  - Invited commentary.

PMID- 20046556
TI  - Beyond SpPIN and SnNOUT: Considerations with Dichotomous Tests During Assessment
      of Diagnostic Accuracy.
AB  - Paramount to efficient and effective care is the determination of an accurate
      diagnosis that leads to the proper referral and/or intervention. In an effort to
      improve the clinical utility of diagnostic accuracy calculations, researchers
      have promoted the use of the mnemonics SpPIn (if specificity is high, a positive
      test rules in pathology) and SnNOut (if sensitivity is high, a negative test
      rules out pathology). Using examples from diagnostic accuracy studies and a
      review of pertinent literature, this clinimetrics corner outlines additional
      considerations for clinicians when consuming research in this area. The paper has
      three foci. First, sensitivity, specificity, and other estimates of the
      diagnostic accuracy of dichotomous physical examination tests should be viewed as
      estimates with confidence when those estimates are expressed as confidence
      intervals. Second, appropriate power must be considered when evaluating each
      study. Last, the quality of a diagnostic accuracy study can affect the
      generalizibility of the results to practice environments.

PMID- 20046557
TI  - Short-term effect of muscle energy technique on pain in individuals with non
      specific lumbopelvic pain: a pilot study.
AB  - Muscle energy technique (MET) is a form of manual therapy frequently used to
      correct lumbopelvic pain (LPP), herein the patient voluntarily contracts specific
      muscles against the resistance of the clinician. Studies on MET regarding
      magnitude and duration of effectiveness are limited. This study was a randomized
      controlled trial in which 20 subjects with self-reported LPP were randomized into
      two groups (MET or control) after magnitude of pain was determined. MET of the
      hamstrings and iliopsoas consisted of four 5-second hold/relax periods, while the
      control group received a sham treatment. Tests for current and worst pain, and
      pain with provocation were administered at baseline, immediately following
      intervention and 24 hours after intervention. Separate 2x3 ANOVAs were used to
      assess results as change scores. Visual analog score (VAS) for worst pain
      reported in the past 24 hours decreased for the MET group (4.3mm+/-19.9, p=.03)
      and increased for the sham (control) group (17.1mm+/-21.2, p=.03). Subjects
      receiving MET demonstrated a decrease in VAS worst pain over the past 24 hours,
      thereby suggesting that MET may be useful to decrease LPP over 24 hours.

PMID- 20046558
TI  - Needle EMG Response of Lumbar Multifidus to Manipulation in the Presence of
      Clinical Instability.
AB  - A proposed mechanism for the persistence of low back pain due to clinical
      instability is a decrease in control of local spinal musculature, more
      specifically decreased recruitment of multifidus. Altered segmental
      mechanoreceptor input has been proposed as a contributing factor responsible for
      a decrease in local muscle recruitment. In this case report, immediate changes in
      the recruitment of the deep multifidus following manipulation were examined using
      needle EMG and isometric testing of trunk rotational force. Trunk rotational
      force appeared to improve while the multifidus demonstrated a decrease in
      activity as measured by needle EMG. No specific conclusions can be drawn from
      this report; however, the results do suggest that immediate multifidus function
      may be influenced with manipulation, resulting in improved muscular control of
      the trunk.

PMID- 20046559
TI  - Does scapula taping facilitate recovery for shoulder impingement symptoms? A
      pilot randomized controlled trial.
AB  - Scapula taping is a commonly used adjunctive treatment for shoulder impingement
      pathology. However, this intervention has not previously been subject to formal
      investigation. A pilot single-blind randomized controlled trial was conducted to
      evaluate facilitatory taping as an adjunct to routine physiotherapy management.
      Twenty-two subjects with unilateral shoulder impingement symptoms were randomized
      into a taping with routine physiotherapy or a routine physiotherapy only group.
      The intervention group had scapula taping applied three times per week for the
      first two weeks of their treatment. All subjects were assessed at baseline, then
      at 2 and 6 weeks after the commencement of treatment. Pain and functional ability
      were assessed using the Shoulder Pain and Disability Index, range of shoulder
      elevation, and self-reported pain on elevation. At 2 weeks, the taping group
      demonstrated a strong trend toward reduced pain both on self-reported activity
      (SPADI pain subscale mean for taping 27.0 versus 41.5 for control) and pain
      during measured abduction (mean VAS 22.8 for taped, 46.8 for control),
      statistical power being limited by small sample size. No similar trend was
      evident in the SPADI disability subscale. The magnitude of the differences was
      reduced at 6-week follow-up. This study provides preliminary evidence for a short
      term role for scapula taping as an adjunct to routine physiotherapy in the
      management of shoulder impingement symptoms but also highlights the need for
      consideration on a case basis relating to risk factors for skin reaction.

PMID- 20046560
TI  - Is clinical gestalt good enough?

PMID- 20046561
TI  - Clinical perspective: how do clinical test results differentiate chronic and
      subacute low back pain patients from "non-patients"?
AB  - Our limited understanding of underlying conditions for back pain is reflected in
      the common use of pain-duration-based groupings. The aim of this paper was to
      investigate typical clinical tests used in examining low back pain (LBP) patients
      in order to discover how tests distinguish between chronic low back pain patients
      (CLBP) and subacute low back pain patients (SLBP) and if they distinguish these
      groups from those with no "patient status." CLBP patients in this study were from
      a university hospital and SLBP patients were from five occupational health care
      centers. Control subjects were recruited from a university. Determination of the
      best predictors between CLBP and SLBP patients and between CLBP and SLBP patients
      and non-patients was made by a forward stepwise logistic model. A total of 157
      subjects were included in the study. Of all the clinical tests, several tests in
      each category had high odds ratio, differentiating CLBP patients from controls.
      Only a few tests differentiated between CLBP and SLBP patients. The only clinical
      differences between SLBP patients and controls were in the mobility test and in
      one test of muscle tightness. The best predictor for CLBP was the lumbar spine
      flexion test. SLBP patients seemed to differ from the control group in lumbar
      flexion, in a specific anterior-posterior mobility test, and in tightness of hip
      flexor muscles. CLBP patients differed from SLBP patients in functional tests, in
      the presence of sensation in the feet, and in different pain provocation tests.
      Whether these tests are sufficiently sensitive to classify a more specific
      diagnostic or clinical subgroup remains untested, and further studies with
      clinical tests to differentiate among pathological conditions are necessary.

PMID- 20046562
TI  - Invited commentary.

PMID- 20046563
TI  - Validity of the McMurray's Test and Modified Versions of the Test: A Systematic
      Literature Review.
AB  - Clinical assessment of meniscal pathology in the knee has proven difficult due to
      the wide number of tests available and variations in their interpretation and
      application. The purpose of this paper was to assess the literature investigating
      the validity and diagnostic accuracy of the McMurray's test (and modifications)
      for determining meniscal pathology of the knee so that conclusions could be drawn
      regarding its clinical usefulness as a test. Electronic databases (Medline,
      CINhAL, AMED, SPORTSDiscus, and SCOPUS) were searched from March 1980 to May
      2008. In addition, cited references of relevant articles were examined. Studies
      were included for analysis if they compared the McMurray's test with a gold
      standard of knee arthroscopy or magnetic resonance imaging (MRI). Eleven studies
      met the inclusion criteria. Collectively, these studies indicate that there is
      little consensus in the reported measures of validity of the McMurray's test and
      that this is mostly due to limitations in the methodological quality of the
      studies that were assessed. Methodological scores on the STARD (Standards for
      Reporting of Diagnostic Accuracy) yielded scores from 10/25 to 20/25. Generally,
      the McMurray's test has relatively high specificity and low sensitivity. The
      studies that compared the diagnostic accuracy of the McMurray's test with that of
      modified versions of the test showed enhanced diagnostic accuracy for the
      modified tests. This review identified that the McMurray's test is of limited
      clinical value due to relatively low sensitivity, with modified tests (associated
      with the traditional McMurray's test) having higher diagnostic accuracy and thus
      these may be more useful clinically.

PMID- 20046564
TI  - Prescriptive clinical prediction rules in back pain research: a systematic
      review.
AB  - Prescriptive clinical prediction rules (CPRs) are a way of using a small
      selection of clinical findings to match patients to optimal interventions. A
      number of CPRs have been developed for use with back pain patients, but these
      have not been systematically reviewed. The purpose of this review was to evaluate
      existing CPRs against established criteria to determine the quality of the
      studies and the overall development of the CPR against a set number of stages.
      Medline was searched up until June 2008, and 16 studies were reviewed that
      related to 9 different CPRs. These studies investigated and attempted to find
      clinical characteristics for responders to manipulation, stabilization exercise,
      physical therapy, chiropractic, traction, rehabilitation, usual care, and
      zygapophyseal joint injections. Eleven of these studies related to the derivation
      stage and five to the validation stage. The manipulation and stabilization CPRs
      had been the most studied. The derivation studies were mostly high quality,
      whereas none of the validation studies were. Some of the validation studies did
      not provide evidence that validated the CPR. Most of these CPRs need further
      evaluation before they can be applied clinically; most did not pass the lowest
      level of evidence hierarchy. As regards the manipulation CPR, evidence to date
      for its clinical utility is limited and contradictory. For the stabilization CPR,
      there was limited evidence that it may be considered but only with caution and in
      similar patients. Overall, there is limited evidence to support the general
      application of spinal CPRs.

PMID- 20046565
TI  - Vertebral Artery Blood flow Velocity Changes Associated with Cervical Spine
      rotation: A Meta-Analysis of the Evidence with implications for Professional
      Practice.
AB  - Many studies of vertebral artery (VA) blood flow changes related to cervical
      spine rotation have been published, but the findings are controversial and the
      evidence unconvincing. Recent Doppler measurements suggest that contralateral VA
      blood flow is compromised on full rotation in both healthy subjects and patients.
      More rigorous research is needed, and it was the aim of this study to conduct a
      meta-analysis of published data to inform professional practice. A systematic
      literature search, including only Doppler studies of VA blood flow velocity
      associated with cervical spine rotation in adults, yielded nine reports with
      published data. Using weighted means of the pooled data, the magnitude of the
      effect size (Cohen's d) was calculated for differences between patients and
      subjects, sitting or lying supine for testing, the parts of the VA insonated, and
      the changes recorded after cervical spine rotation. From this meta-analysis, VA
      blood flow velocity was found to be compromised more in patients than healthy
      individuals, on contralateral rotation, with the subject sitting, and more in the
      intracranial compared to the cervical part of the VA. Possible reasons for these
      findings are suggested, and it is advised that sustained end-of-range rotation
      and quick-thrust rotational manipulations be avoided until there is a stronger
      evidence base for clinical practice.

PMID- 20046566
TI  - Positional stretching of the coracohumeral ligament on a patient with adhesive
      capsulitis: a case report.
AB  - Idiopathic frozen shoulder is a common medical diagnosis for patients seeking
      physical therapy. Radiographic and surgical evidence exists that describes the
      coracohumeral ligament (CHL) as a major contributor to lack of external rotation
      in patients diagnosed with frozen shoulder. No stretching techniques targeting
      the anatomical fiber orientation of the CHL have been reported in the literature.
      This single-patient case-report describes the use of a positional stretching
      technique of the CHL on a 51-year-old female diagnosed with phase I frozen
      shoulder. The patient completed 8 in-office visits and 17 home exercise program
      sessions of positional CHL stretching combined with a simple volitional rotator
      cuff exercise program in a 4-week period. The patient's Disabilities of the Arm
      Shoulder and hand (DASH) scores improved from 65 to 36 and Shoulder Pain and
      Disability Index (SPADI) scores improved from 72 to 8 and passive external
      rotation from 20 degrees to 71 degrees . While a cause-and-effect relationship
      cannot be inferred from a single case, this report may foster further
      investigation regarding the role of the CHL in patients with stage-I and stage-II
      frozen shoulder as well as therapeutic strategies to help reduce loss of mobility
      and function.

PMID- 20046568
TI  - Practical considerations for nonclinical safety evaluation of therapeutic
      monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) are a well established class of therapeutics as
      evidenced by a large number of FDA approved mAbs for the treatment of cancers and
      autoimmune diseases. Monoclonal antibodies that are molecularly engineered for
      enhanced functions and pharmacokinetic properties are routinely being considered
      for development by many biotechnology companies. Safety evaluation of current
      generation of mAbs poses new challenges due to the highly complex nature of
      engineering aspects and variability induced by the diverse recombinant cell
      systems to generate them. This review provides a basic outline for nonclinical
      safety evaluation of therapeutic antibodies. Important considerations for
      planning a preclinical program, the types of nonclinical safety studies, and a
      general timeline for their conduct in relation to clinical trials are described.
      A list of relevant regulatory documents issued by government agencies is also
      provided. Adoption of these principles will greatly enhance the quality and
      relevance of the nonclinical safety data generated and will facilitate future
      development of mAb therapeutics.

PMID- 20046570
TI  - Engineered CH2 domains (nanoantibodies).
AB  - Currently, almost all FDA approved therapeutic antibodies (except ReoPro,
      Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical
      trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A
      fundamental problem for such large molecules is their poor penetration into
      tissues (e.g., solid tumors) and poor or absent binding to regions on the surface
      of some molecules (e.g., on the HIV envelope glycoprotein) which are fully
      accessible only by molecules of smaller size. Therefore, much work especially
      during the last decade has been aimed at developing novel scaffolds of much
      smaller size and high stability. Here I briefly describe a proposition to use the
      immunoglobulin (Ig) constant CH2 domain (CH3 for IgE and IgM) as a scaffold. CH2
      is critical for the Ig effector functions. Isolated CH2 is stable monomer in
      contrast to all other constant domains and most of the variable domains. CH2 and
      engineered CH2 domains with improved stability can be used as scaffolds for
      construction of libraries containing diverse binders to various antigens. Such
      binders based on a CH2 scaffold could also confer some effector functions.
      Because the CH2 domains are the smallest independently folded antibody domains
      that can be engineered to contain simultaneously antigen-binding sites and
      binding sites mediating effector and stability functions, and to distinguish them
      from domain antibodies which are used to denote engineered VH or VL domains or
      nanobodies which are used to denote camelid VHH, I termed them nanoantibodies
      (nAbs).

PMID- 20046571
TI  - Are mAbs different?: a comment on Cohen and Wilson.

PMID- 20046569
TI  - Antibodies targeting cancer stem cells: a new paradigm in immunotherapy?
AB  - Antibody targeting of cancer is showing clinical and commercial success after
      much intense research and development over the last 30 years. They still have the
      potential to delivery long-term cures but a shift in thinking towards a cancer
      stem cell (CSC) model for tumor development is certain to impact on how
      antibodies are selected and developed, the targets they bind to and the drugs
      used in combination with them. CSCs have been identified from many human tumors
      and share many of the characteristics of normal stem cells. The ability to renew,
      metabolically or physically protect themselves from xenobiotics and DNA damage
      and the range of locomotory-related receptors expressed could explain the
      observations of drug resistance and radiation insensitivity leading to metastasis
      and patient relapse.Targeting CSCs could be a strategy to improve the outcome of
      cancer therapy but this is not as simple as it seems. Targets such as CD133 and
      EpCAM/ESA could mark out CSCs from normal cells enabling specific intervention
      but indirect strategies such as interfering with the establishment of a
      supportive niche through anti-angiogenic or anti-stroma therapy could be more
      effective.This review will outline the recent discoveries for CSCs across the
      major tumor types highlighting the possible molecules for intervention. Examples
      of antibody-directed CSC therapies and the outlook for the future development of
      this emerging area will be given.

PMID- 20046573
TI  - Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of
      epithelial origin.
AB  - Nimotuzumab is a humanized therapeutic monoclonal antibody against epidermal
      growth factor receptor (EGFR). Clinical trials are ongoing globally to evaluate
      nimotuzumab in different indications. Nimotuzumab has been granted approval for
      use in squamous cell carcinoma of head and neck (SCCHN), glioma and
      nasopharyngeal cancer in different countries. This review focuses on the unique
      functional characteristics of nimotuzumab. Also, it discusses the safety and
      efficacy data obtained from the Phase IIb clinical trial conducted in India in
      SCCHN. Post marketing surveillance data from Cuba for the use of nimotuzumab in
      pediatric and adult glioma is also discussed. Overall, nimotuzumab has immense
      therapeutic potential in cancers of epithelial origin.

PMID- 20046572
TI  - Combination bortezomib and rituximab treatment affects multiple survival and
      death pathways to promote apoptosis in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a distinct histologic subtype of B cell non
      Hodgkins lymphoma (NHL) associated with an aggressive clinical course. Inhibition
      of the ubiquitin-proteasome pathway modulates survival and proliferation signals
      in MCL and has shown clinical benefit in this disease. This has provided
      rationale for exploring combination regimens with B-cell selective
      immunotherapies such as rituximab. In this study, we examined the effects of
      combined treatment with bortezomib and rituximab on patient-derived MCL cell
      lines (Jeko, Mino, SP53) and tumor samples from patients with MCL where we
      validate reversible proteasome inhibition concurrent with cell cycle arrest and
      additive induction of apoptosis. When MCL cells were exposed to single agent
      bortezomib or combination bortezomib/rituximab, caspase dependent and independent
      apoptosis was observed. Single agent bortezomib or rituximab treatment of Mino
      and Jeko cell lines and patient samples resulted in decreased levels of nuclear
      NFkappaB complex(es) capable of binding p65 consensus oligonucleotides, and this
      decrease was enhanced by the combination. Constitutive activation of the Akt
      pathway was also diminished with bortezomib alone or in combination with
      rituximab. On the basis of in vitro data demonstrating additive apoptosis and
      enhanced NFkappaB and phosphorylated Akt depletion in MCL with combination
      bortezomib plus rituximab, a phase II trial of bortezomib-rituximab in patients
      with relapsed/refractory MCL is underway.

PMID- 20046574
TI  - Two doses of humanized anti-CD25 antibody in renal transplantation: a preliminary
      comparative study.
AB  - HuCD25mAb is a humanized anti-CD25 antibody which has the same amino acid
      sequence as daclizumab (Zenapax, Roche). HuCD25mAb is expressed in Chinese
      hamster ovary (CHO) cells while daclizumab is expressed in the NSO myeloma cell
      line. A comparative study was performed to evaluate the pharmacokinetics and
      pharmacodynamics between huCD25mAb and daclizumab in a two-dose regimen
      incorporating triple immunosuppressant treatment regimens (MMF, CsA and
      steroids). Fifteen patients were enrolled and randomized to receive intravenous
      infusion of either huCD25mAb (n = 10) or daclizumab (n = 5) at a dosage of 1
      mg.kg(-1) on operation day 0 and post-operation day 14. Serum concentrations of
      huCD25mAb and daclizumab were measured by a validated competitive ELISA.
      Subgroups of CD3(+), CD25(+), CD4(+) and CD8(+) lymphocytes were monitored
      periodically by flow cytometry. The concentration-time curves of huCD25mAb and
      daclizumab were found to fit well to a one-compartment model. A significant
      decline of proportion (%) of CD3-CD25(+) and CD3(+)CD25(+) lymphocytes was
      observed 30 min after first infusion on day 0 (3.40 +/- 1.83 to 0.03 +/- 0.07,
      3.35 +/- 2.02 to 0.37 +/- 0.49), and these levels remained low for at least 70
      days (0.03 +/- 0.05, 0.31 +/- 0.47). All pharmacokinetic parameters of huCD25mAb
      seemed similar to those of daclizumab. The two-dose huCD25mAb regimen was as
      effective as daclizumab in rapidly achieving high therapeutic concentration in
      the treated patients, and a significant decrease of CD3(-)CD25(+) and
      CD3(+)CD25(+) lymphocytes was demonstrated. This suggests that two-dose regimen
      is feasible in maintaining host immunosuppression and may provide an effective
      and economical strategy for reducing incidence of acute graft rejection.

PMID- 20046575
TI  - New challenges to medicare beneficiary access to mAbs.
AB  - Precision binding of monoclonal antibodies (mAbs) to biological targets, their
      relative clinical success, and expansion of indications following initial
      approval, are distinctive clinical features. The relatively high cost of mAbs,
      together with the absence of a regulatory pathway to generics, stand out as
      distinctive economic features. Based on both literature review and primary data
      collection we enumerated mAb original approvals, supplemental indications and off
      label uses, assessed payer formulary management of mAbs, and determined new
      challenges to Medicare beneficiary access to mAbs. We found that the FDA has
      approved 22 mAbs and 30 supplemental indications pertaining to the originally
      approved mAbs. In addition, there are 46 off-label use citations in officially
      recognized pharmaceutical compendia. Across Part B carriers and Part D plans, we
      found considerable variation in terms of coverage and conditions of reimbursement
      related to on- and off-label uses of mAbs. Our results point to four major
      challenges facing mAb developers, health care providers, Medicare beneficiaries,
      payers and policymakers. These include administrative price controls, coverage
      variation, projected shift from physician- to self-administered mAbs, and
      comparative effectiveness. We suggest more systematic use of "coverage with
      evidence development" as a means of optimally addressing these challenges.

PMID- 20046576
TI  - How can we improve antibody-based cancer therapy?
AB  - Monoclonal antibodies (mAbs) as a class of novel oncology therapeutics are
      demonstrating clinical efficacy as measured by tumor response (shrinkage in tumor
      size), and prolongations in progression-free survival (PFS) and overall survival
      (OS). However, clinical benefits are often limited to when antibodies are used in
      combination with chemotherapy or radiation modalities, with tumor responses only
      seen in a fraction of patients, and improvements in PFS and OS are incremental.1
      The potential of mAbs and mAb constructs has yet to be fully exploited for
      maximal clinical benefit. New approaches to further improve the effectiveness of
      these mAb therapies include (1) selection of patients who may derive the most
      benefit based on the molecular characteristics of their tumors; (2) improvements
      in biodistribution to maximize delivery of mAbs to susceptible tumor cells; and
      (3) optimization of antibody immune effector mechanisms such as antibody
      dependent cellular cytotoxicity (ADCC).

PMID- 20046579
TI  - About our Editors.

PMID- 20046580
TI  - Letter from the editors.
AB  - Dermato-Endocrinology, is a new platform for clinicians and scientists interested
      in the role of the skin as an endocrine, autocrine or paracrine organ.

PMID- 20046578
TI  - Global antibody development trends.

PMID- 20046577
TI  - Antibodies designed as effective cancer vaccines.
AB  - Antigen/antibody complexes can efficiently target antigen presenting cells to
      allow stimulation of the cellular immune response. Due to the difficulty of
      manufacture and their inherent instability complexes have proved inefficient
      cancer vaccines. However, anti-idiotypic antibodies mimicking antigens have been
      shown to stimulate both antibody and T cell responses. The latter are due to T
      cell mimotopes expressed within the complementarity-determining regions (CDRs) of
      antibodies that are efficiently presented to dendritic cells in vivo. Based on
      this observation we have designed a DNA vaccine platform called ImmunoBody, where
      cytotoxic T lymphocyte (CTL) and helper T cell epitopes replace CDR regions
      within the framework of a human IgG1 antibody. The ImmunoBody expression system
      has a number of design features which allow for rapid production of a wide range
      of vaccines. The CDR regions of the heavy and light chain have been engineered to
      contain unique restriction endonuclease sites, which can be easily opened, and
      oligonucleotides encoding the T cell epitopes inserted. The variable and constant
      regions of the ImmunoBody are also flanked by restriction sites, which permit
      easy exchange of other IgG subtypes. Here we show a range of T cell epitopes can
      be inserted into the ImmunoBody vector and upon immunization these T cell
      epitopes are efficiently processed and presented to stimulate high frequency
      helper and CTL responses capable of anti-tumor activity.

PMID- 20046581
TI  - Shining light on the vitamin D: Cancer connection IARC report.

PMID- 20046582
TI  - Inhibition of prostaglandin synthesis and actions contributes to the beneficial
      effects of calcitriol in prostate cancer.
AB  - Our research is aimed at obtaining a better understanding of the molecular
      mechanisms of the anti-proliferative and cancer preventive effects of calcitriol
      with the goal of developing strategies to improve the treatment of prostate
      cancer (PCa). In PCa cells calcitriol inhibits the synthesis and biological
      actions of prostaglandins (PGs) by three actions: (i) the inhibition of the
      expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the
      upregulation of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the
      enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG
      receptors that are essential for PG signaling. Since PGs have been shown to
      promote carcinogenesis and progression of multiple cancers, we hypothesize that
      the inhibition of the PG pathway contributes to the ability of calcitriol to
      prevent or inhibit PCa development and growth. We have shown that the combination
      of calcitriol and non-steroidal anti-inflammatory drugs (NSAIDs) result in a
      synergistic inhibition of the growth of PCa cell cultures and this combination
      therapy offers a potential therapeutic strategy. These findings led us to embark
      on a clinical trial combining the non-selective NSAID naproxen with calcitriol in
      men with early recurrent PCa. The results indicate that the combination of high
      dose weekly calcitriol with naproxen slows the rate of rise (doubling time) of
      PSA in most patients indicating the slowing of disease progression. Further
      studies are warranted to determine the role of this combination therapy in the
      management of recurrent PCa.

PMID- 20046583
TI  - Acne, dairy and cancer: The 5alpha-P link.
AB  - A potent link to dairy seems to exist for three hormone-responsive glands. Acne,
      breast cancer and prostate cancer have all been linked epidemiologically to dairy
      intake. Although mechanisms postulated here remain to be accurately defined, the
      likely link involves Insulin-like Growth Factor-1 as a general stimulant,
      synergized by the steroid hormones present in milk. The IGF-1 may be either
      absorbed from milk, or stimulated by its ingestion, or both. The 5alpha-reduced
      compound 5alpha-pregnanedione (5alpha-P) present in milk is a direct precursor of
      dihydrotestosterone and may act through that pathway in prostate cancer, but
      5alpha-P has also recently been shown to be capable of inducing estrogen
      receptors in breast cancer cells, upregulating cancer cells' sensitivity to
      estrogen. The introduction of exogenous hormones and growth factors into tissues
      that have not evolved defensive feedback inhibition of their corresponding
      endogenous sources is postulated as a direct stimulatory threat to these organ
      systems, whether for hyperplasia or neoplasia.

PMID- 20046584
TI  - How strong is the evidence that solar ultraviolet B and vitamin D reduce the risk
      of cancer?: An examination using Hill's criteria for causality.
AB  - The ultraviolet-B (UVB)-vitamin D-cancer hypothesis was proposed in 1980. Since
      then, several ecological and observational studies have examined the hypothesis,
      in addition to one good randomized, controlled trial. Also, the mechanisms
      whereby vitamin D reduces the risk of cancer have been elucidated. This report
      aims to examine the evidence to date with respect to the criteria for causality
      in a biological system first proposed by Robert Koch and later systematized by A.
      Bradford Hill. The criteria of most relevance are strength of association,
      consistency, biological gradient, plausibility/mechanisms and experimental
      verification. Results for several cancers generally satisfy these criteria.
      Results for breast and colorectal cancer satisfy the criteria best, but there is
      also good evidence that other cancers do as well, including bladder, esophageal,
      gallbladder, gastric, ovarian, rectal, renal and uterine corpus cancer, as well
      as Hodgkin's and non-Hodgkin's lymphoma. Several cancers have mixed findings with
      respect to UVB and/or vitamin D, including pancreatic and prostate cancer and
      melanoma. Even for these, the benefit of vitamin D seems reasonably strong.
      Although ecological and observational studies are not generally regarded as able
      to provide convincing evidence of causality, the fact that humanity has always
      existed with vitamin D from solar UVB irradiance means that there is a wealth of
      evidence to be harvested using the ecological and observational approaches.
      Nonetheless, additional randomized, controlled trials are warranted to further
      examine the link between vitamin D and cancer incidence, survival and mortality.

PMID- 20046585
TI  - A critical review of Vitamin D and Cancer: A report of the IARC Working Group.
AB  - The International Agency for Research on Cancer (IARC) released a report, Vitamin
      D and Cancer, on November 25, 2008. The report focused on the current state of
      knowledge and level of evidence of a causal association between vitamin D status
      and cancer risk. Although presenting and evaluating evidence for the beneficial
      role of UVB and vitamin D in reducing the risk of cancer, it discounted or
      omitted important evidence in support of the efficacy of vitamin D. The report
      largely dismissed or ignored ecological studies on the grounds that confounding
      factors might have affected the findings. The report accepted a preventive role
      of vitamin D in colorectal cancer but not for breast cancer.The only randomized
      controlled trial (RCT) on cancer incidence that used a sufficiently high dose of
      vitamin D (1,100 IU/day) and calcium (1,400-1,500 mg/day) found a 77% reduction
      in the risk of all-cancer incidence in postmenopausal women who received both, of
      which approximately 35% reduction in risk was attributed to vitamin D alone.
      Unfairly, the report dismissed these findings on the basis of a flawed
      critique.The report called for RCTs of vitamin D supplementation to settle the
      issue. Although RCTs theoretically would be beneficial, development of sound and
      effective public health policies does not necessarily depend on them, and the
      field of vitamin D, calcium and chronic disease has reached the point where RCTs
      may not be ethical.The IARC report should therefore not form the basis for public
      health policy decisions.

PMID- 20046586
TI  - Acquired ichthyosis associated with type 1 diabetes mellitus.
AB  - Acquired ichthyosis is an uncommon disease which is characterized by symmetric
      scaling of the skin. Acquired ichthyosis has been described in association with a
      variety of underlying causes, including malignancies, drugs, infections,
      endocrine, metabolic and autoimmune diseases. Acquired ichthyosis associated with
      diabetes mellitus has been reported only in one case. We report the case of a new
      onset diabetes mellitus with a one-month history of generalized acquired
      ichthyosis and palmoplantar keratoderma corroborated with skin biopsy, which
      completely disappeared after regulation of blood glucose levels with insulin
      therapy.

PMID- 20046587
TI  - Solar ultraviolet-B irradiance and vitamin D may reduce the risk of septicemia.
AB  - The primary features of the epidemiology of septicemia in the United States
      include highest rates in winter and the Northeast, lowest in fall and in the
      West; higher rates among African Americans than white Americans; a rapid increase
      in incidence with age; comorbidity with several chronic and infectious diseases;
      and a rapid increase in incidence rate starting in the early 1980s. This article
      reviews the literature on the epidemiology of septicemia in the United States,
      along with the roles of solar ultraviolet-B (UVB) and vitamin D3 related to the
      more important features. Solar UVB doses in summer are highest in the Southwest
      and lowest in the Northeast. Serum 25-hydroxyvitamin D [25(OH)D] levels are
      highest in summer, lowest in winter. African Americans have much lower 25(OH)D
      levels than those of white Americans. Serum 25(OH)D levels decline rapidly with
      advancing age. The risk of diseases comorbid with septicemia are generally
      inversely correlated with serum 25(OH)D levels. Sun-avoidance messages may have
      led to lower population levels of 25(OH)D, although prevalence of antibiotic
      resistant bacteria may have increased. Previous reports have shown that 1,25
      dihydroxyvitamin D upregulates human cathelicidin, LL-37, which has antimicrobial
      as well as antiendotoxin activity. The general agreement between the epidemiology
      of septicemia in the United States and the variations of solar UVB and the
      effects of vitamin D supports the hypothesis that both play important roles in
      reducing the risk of septicemia. Further study is warranted to evaluate this
      hypothesis.

PMID- 20046588
TI  - Vitiligo vulgaris and autoimmune diseases in Japan: A report from vitiligo clinic
      in Kyoto University Hospital.
AB  - We reviewed the causes of "loss of skin color" in 144 patients, who visited
      Vitiligo Clinic of Kyoto University Hospital between April 2005 and August 2008.
      The numbers of patients with generalized and segmental Vitiligo vulgaris were 98
      (68.1%) and 26 (18.1%), respectively. Small numbers of the patients suffered from
      Vogt-Koyanagi-Harada disease, piebaldism, congenital albinism, Hypomelanosis of
      Ito, post-inflammatory hypopigmentation, white leaf-shaped macules associated
      with tuberous sclerosis and nevus hypopigmentosus. One forth of the patients with
      generalized vitiligo had complications, while no complications were found in the
      patients with segmental vitiligo. Among the complications, autoimmune diseases
      dominated 43% (10 of 23 cases). Autoimmune thyroid diseases explained for the
      most of the complicated autoimmune diseases and were associated with 7.4% of the
      patients with generalized vitiligo. Minor autoimmune complications include
      myasthenia gravis, Sjogren syndrome and autoimmune nephritis. Reflecting the
      condition that our clinic is located in a university hospital, vitiligo patients
      with end-stage non-melanoma cancers of internal organs accounted for 8.4% of the
      patients of generalized vitiligo.

PMID- 20046589
TI  - Hair-cycle dependent differential expression of ADAM 10 and ADAM 12: An
      immunohistochemical analysis in human hair follicles in situ.
AB  - BACKGROUND: ADAM proteases play important roles in processes of development and
      differentiation. However, no report has been found in the literature addressing
      the expression and function of ADAM proteases during hair cycling. RESULTS:
      Cytoplasmic expression pattern of ADAM 10, 12 was similar between normal
      epidermis and hair infundibulum. In addition, cytoplasmic expression of ADAM 10
      was observed in the hair bulb keratinocytes and fibroblasts of dermal papilla in
      anagen I-III hair follicles. In contrast, decreased ADAM 10 expression was
      observed in the hair matrix keratinocytes as compared to the hair bulb
      keratinocytes in anagen I-III hair follicles. Interestingly, ADAM 10
      immunoreactivity was expressed weakly in the lower portion of outer root sheath
      (ORS) of anagen VI hair follicles, and strong ADAM 10 expression was detected in
      the ORS of catagen and telogen hair follicles. By contrast, ADAM 12 expression
      was not detected in the hair bulb keratinocytes of anagen I-III hair follicles.
      ADAM 12 immunoreactivity firstly appeared in the inner root sheath ( IRS ) of
      anagen IV-V hair follicles and was down-regulated in the IRS and hair cortex and
      medulla of catagen hair follicles, Strong ADAM 12 immunoreactivity was observed
      in the ORS of catagen and telogen hair follicles. MATERIAL AND METHODS: Samples
      of normal human skin (n = 30) were used. Immunohistochemical analysis was
      performed using ADAM 10, 12 specific polyclonal antibodies and a sensitive
      streptavidin-peroxidase technique. CONCLUSION: Our study demonstrates a
      comparable staining pattern of decreased ADAM 10 immunoreactivity in hair matrix
      keratinocytes and the basal cell layer of normal epidermis and hair infundibulum.
      Expression of ADAM 10 in dermal papilla cells may imply a role in the induction
      and development of anagen hair follicles. In addition, expression of ADAM 10 in
      the ORS and hair bulb assume the involvment of ADAM 10 in the downward migration
      of anagen hair follicles. Furthermore ADAM 12 expression in the IRS may indicate
      a role in the differentiation of anagen hair follicles. Downregulation of ADAM 12
      upon the onset of catagen hair stage suggests that ADAM 12 may play an important
      role of ADAM 12 in the apoptosis of hair follicle keratinocytes. In summary our
      findings suggest that ADAM 10 and 12 may be of importance for the regulation of
      hair cycling.

PMID- 20046591
TI  - Congenital woolly hair without P2RY5 mutation.
AB  - Congenital woolly hair is a disorder with structural defects of the hair shafts.
      Curled hairs are noticed at birth or soon after birth and often improve with age.
      Some cases of woolly hairs are associated with systemic or other skin diseases.
      Congenital woolly hair without any associated disorder is inherited in an
      autosomal dominant or autosomal recessive manner. Recently, mutations in P2RY5
      gene, encoding a G-protein coupled receptor, have been shown to be responsible
      for autosomal recessive woolly hair. Here, we report the second Japanese case of
      congenital woolly hair, showing no P2RY5 gene mutation.

PMID- 20046590
TI  - The unfavorable effect of the A allele of the vitamin D receptor promoter
      polymorphism A-1012G has different mechanisms related to susceptibility and
      outcome of malignant melanoma.
AB  - The A allele of the A-1012G (rs4516035) vitamin D receptor (VDR) promoter
      polymorphism is associated with increased susceptibility and worsened outcome in
      malignant melanoma (MM). The A allele contains a GATA-3 binding site. There is a
      second polymorphism in the same promoter region, G-1520C (rs7139166), and there
      is potential for another GATA binding site in the G allele. Here, we tested the
      hypothesis that the G(-1520)A(-1012) haplotype might be a greater risk factor for
      MM than A-1012 alone. The A allele of A-1012G was preferentially linked to G of G
      1520C and was more frequent in MM patients (p = 0.011) but G of G-1520C was not
      (p = 0.756). The CA haplotype was a very significant risk factor for MM (p =
      0.0001) while the CG haplotype was protective (p = 0.014, combined model p =
      0.00002). There was no effect of GA haplotype (p = 0.931), suggesting that that
      the difference in frequencies of the A allele between patients and controls was
      accounted for by the differences in frequencies of the CA haplotype. The A allele
      of A-1012G was more frequent in patients with metastasis (p = 0.054) than MM
      patients without metastasis, as was the G allele of G-1520C (p = 0.028). The GA
      haplotype was more frequent in patients with metastasis (p = 0.015), while
      frequencies of CA were similar. We suggest that the different roles of the A
      allele of A-1012G in susceptibility and metastasis risk may be a function of the
      availability of transcription factors in the differing cellular backgrounds
      related to susceptibility and progression of MM.

PMID- 20046592
TI  - Central or atypical skull base osteomyelitis: diagnosis and treatment.
AB  - OBJECTIVE: We report cases of central or atypical skull base osteomyelitis and
      review issues related to the diagnosis and treatment. METHODS: The four cases
      presented, which were drawn from the Oxford, United Kingdom, skull base pathology
      database, had a diagnosis of central skull base osteomyelitis. RESULTS: Four
      cases are presented in which central skull base osteomyelitis was diagnosed.
      Contrary to malignant otitis externa, our cases were not preceded by immediate
      external infections and had normal external ear examinations. They presented with
      headache and a variety of cranial neuropathies. Imaging demonstrated bone
      destruction, and subsequent microbiological analysis diagnosed infection and
      prompted prolonged antibiotic treatment. CONCLUSION: We concluded that in the
      diabetic or immunocompromised patient, a scenario of headache, cranial
      neuropathy, and bony destruction on imaging should raise the possibility of skull
      base osteomyelitis, even in the absence of an obvious infective source. The
      primary goal should still be to exclude an underlying malignant cause.

PMID- 20046593
TI  - Sinonasal mucosal melanoma: a 13-year experience at a single institution.
AB  - OBJECTIVE: Report the experience of the Karmanos Cancer Institute with sinonasal
      mucosal melanoma (SNMM) in patients diagnosed between 1995 and 2007. RESULTS:
      Eighteen patients, ages 31 to 85 (mean, 67), whose most common presenting
      symptoms included epistaxis and facial pressure. Most common anatomic locations
      were the maxillary sinus and nasal cavity. Seventy-two percent presented with
      tumors extending to the skull base, frontal sinus, orbit, or cranium. Tumor size
      ranged from 0.3 cm to 5.3 cm. Most common surgical procedure was medial
      maxillectomy (12 patients). Eight patients received chemotherapy, ten received
      radiotherapy and six received both. One third of patients received interferon
      alpha. Median recurrence-free survival (RFS) was 14.4 months, with a 1-year RFS
      rate of 55%. Median overall survival (OS) was 19.3 months with a 1-year OS rate
      of 60% and a 2-year OS rate of 42%. The 5-year OS rate was 34%. CONCLUSION: SNMM
      remains a disease that has eluded breakthroughs in treatment. Patients are
      typically treated with wide local resection; however unique to our institution
      was the frequent use of interferon and chemoradiation. Further research in
      adjuvant therapies will be necessary to improve outcomes.

PMID- 20046595
TI  - Importance of complete pterygomaxillary separation in the le fort I osteotomy: an
      anatomic report.
AB  - This article reports on the presence of an anatomic feature of the extracranial
      skull base that may result in internal carotid artery injury if secure and
      complete pterygomaxillary separation is not achieved before maxillary
      downfracture in the Le Fort I osteotomy. The extracranial skull base of 129 adult
      skulls and 10 pediatric skulls was examined in the region near the foramen
      lacerum. This region was inspected for the presence or absence of a bony
      protrusion that projected posteriorly from the base of the sphenoid, lying
      inferior to the foramen lacerum. The bony protrusion was present bilaterally in
      71% of the adult skulls and 60% of the pediatric skulls. The protrusion was a
      bony "spike" that pointed posteriorly and was located inferior to the foramen
      lacerum on the extracranial skull base. Due to its size, shape, and location, the
      bony protrusion described in this study poses considerable risk to the internal
      carotid artery if the protrusion is displaced superiorly through the foramen
      lacerum. In the Le Fort I osteotomy, secure and complete pterygomaxillary
      separation is crucial to avoid injury to the internal carotid artery during
      maxillary downfracture.

PMID- 20046594
TI  - Surgery for optic nerve injury: should nerve sheath incision supplement osseous
      decompression?
AB  - OBJECTIVE: To evaluate the benefits and risks of performing an optic nerve sheath
      incision to supplement standard osseous optic canal decompression for traumatic
      optic neuropathy. METHODS: Before-after analysis of 57 cases undergoing optic
      nerve decompression at a tertiary referral centre from 1988-2006. Fifty-five
      cases had adequate post surgical follow-up for evaluation for improvement. Group
      A (n = 35) had decompression of the osseous optic canal and surgical slitting of
      the optic nerve sheath; Group B (n = 22) had osseous decompression alone. The
      groups were comparable for age, injury severity, and injury-surgery interval.
      MAIN OUTCOME MEASURE: Percentage visual improvement, which was calculated by
      conversion of the pre- and post-intervention visual acuity measurements to the
      logarithm of the minimum angle of resolution (logMAR) scale. RESULTS: No
      significant recovery was noted in subjects with persistent complete blindness (PL
      ve vision). In subjects with residual pre-op vision, the quantum of recovery was
      greater in Group A than in Group B (46% and 33% respectively, p = 0.10). The
      difference was especially evident in subjects with no optic canal/posterior orbit
      fracture (p = 0.07). Three cases with the sheath incision developed transient CSF
      rhinorrhea in the initial experience, but this was subsequently alleviated with
      modification of surgical technique. CONCLUSION: The addition of optic nerve
      sheath incision to osseous decompression may improve recovery in optic nerve
      injury, especially in subjects without optic canal fracture.

PMID- 20046596
TI  - Refractory cerebrospinal fluid rhinorrhea secondary to occult superior vena cava
      syndrome and benign intracranial hypertension: diagnosis and management.
AB  - OBJECTIVE: This study is designed to describe the association between benign
      intracranial hypertension (BIH) and spontaneous cerebrospinal fluid (CSF)
      rhinorrhea and address the effect of extracranial venous flow dynamics on
      intracranial pressure (ICP). METHODS: We present a 58-year-old woman with
      refractory spontaneous CSF rhinorrhea who was later found to have superior vena
      cava syndrome. The patient had undergone two prior transnasal endoscopic repair
      attempts. In retrospect, a preoperative magnetic resonance venogram (MRV)
      suggested very prolonged cerebral transit time, despite otherwise normal
      intracranial venous anatomy. RESULTS: The CSF leak was repaired through a
      bifrontal craniotomy. The intraoperative and postoperative course was complicated
      due to the patient's significant comorbidities. She ultimately made a good
      recovery and has not had any further CSF rhinorrhea in more than 2 years of
      follow-up. CONCLUSIONS: Refractory, spontaneous CSF leak must prompt aggressive
      investigation for multiple causes of elevated ICP. A cerebral transit time can be
      obtained from scout imaging when a magnetic resonance angiogram or MRV is
      performed, and this may disclose elevated ICP if it is prolonged. If endoscopic
      transnasal repair fails, craniotomy and direct suture repair and autologous
      tissue reinforcement of the skull base may prove successful and durable, even if
      BIH persists.

PMID- 20046597
TI  - Transoral stereotactic technique for clival biopsy.
AB  - OBJECTIVE: To report a transoral freehand technique using continuous image
      guidance to biopsy a clival lesion. METHODS: The patient was placed in a Mayfield
      head rest. Patient data were registered using preacquired magnetic resonance and
      computed tomography images, and then, under continuous image guidance, a bone
      biopsy instrument was advanced freehand through a transoral route into the clival
      lesion. RESULTS: Bone biopsy instrumentation was successfully placed into the
      clival lesion. Biopsy forceps were placed through the working channel of the
      biopsy instrumentation and specimen was successfully retrieved from the clival
      mass. The patient tolerated the procedure well and the only complaint was
      dysphagia, which resolved in several days postoperatively. CONCLUSION: The
      transoral freehand technique with stereotactic navigation was found to be a
      simple, safe, fast, and effective way to biopsy a clival lesion.

PMID- 20046598
TI  - Giant-cell tumors of the temporal bone: management strategies.
AB  - OBJECTIVE: To discuss the current management options for giant-cell tumors (GCTs)
      involving the temporal bone and present two case reports and a review of the
      literature. METHOD: In a tertiary-care academic medical center, two patients with
      GCTs of the temporal bone were evaluated and managed. The patients underwent
      gross total resection and curettage of GCTs involving the temporal bone.
      Afterward, both patients were evaluated for postoperative complications as well
      as for recurrence. RESULTS: Two patients underwent operative excision using
      curettage. Clinical and radiographic studies demonstrated no evidence of
      recurrence with 3 years of follow-up in one patient and 10 years of follow-up in
      the second patient. CONCLUSION: Based on these results, we concluded that gross
      total removal and curettage of GCTs in the temporal bone is a viable treatment
      option. This finding is contrary to previous studies.

PMID- 20046599
TI  - Titanium mesh reconstruction to maintain scalp contour after temporalis
      musculofascial flap reconstruction of the floor of the middle cranial fossa: a
      technical note and report of two cases.
AB  - OBJECTIVE: Temporalis musculofascial rotational flaps can provide excellent
      tissue for reconstruction of defects in the floor of the middle cranial fossa.
      This technique can, however, result in cosmetic deformity of the temporal fossa
      with an asymmetric contour of the head. We report a technique that uses titanium
      mesh and autologous abdominal adipose to maintain a normal scalp contour.
      CLINICAL PRESENTATION: Two patients, one with a large middle cranial fossa and
      infratemporal schwannoma, and another with penetrating trauma secondary to a
      rifle accident, required surgical repair of defects of the floor of the middle
      cranial fossa. INTERVENTION: The repair was achieved in both cases using a
      temporalis musculofascial rotational flap. Normal contour of the scalp was
      maintained with titanium mesh and autologous abdominal adipose reconstruction.
      CONCLUSION: The temporalis musculofascial flap, combined with titanium mesh and
      autologous adipose reconstruction, provided excellent closure of defects of the
      floor of the middle cranial fossa while preserving normal cosmetic scalp contour.

PMID- 20046600
TI  - Poverty in Canada.

PMID- 20046602
TI  - Longitudinal study of the distribution of Mycobacterium avium subsp.
      paratuberculosis in the environment of dairy herds in the Michigan Johne's
      disease control demonstration herd project.
AB  - The objective of this study was to describe the distribution of Mycobacterium
      avium subsp. paratuberculosis (MAP) in the environment of infected dairy farms
      over time. Johne's disease (JD) prevalence was monitored annually in 7 Michigan
      dairy herds. Environmental samples were collected bi-annually and cultured for
      MAP. Of 731 environmental samples that were cultured, 81 (11%) were positive. The
      lactating cow floor and manure storage areas were the areas most commonly
      contaminated, representing 30% and 33% of positive samples, respectively. When
      herd prevalence was > 2%, MAP was cultured from the lactating cow floor and/or
      manure storage area 75% of the time. When herd prevalence was < or = 2%, MAP was
      never cultured from samples collected. For every 1 unit increase in number of
      positive environmental samples, within herd JD prevalence increased 1.62%.
      Environmental contamination with MAP is consistent over time on infected dairy
      farms, and management practices to reduce environmental contamination are
      warranted.

PMID- 20046603
TI  - Occurrence of antimicrobial resistant bacteria in healthy dogs and cats presented
      to private veterinary hospitals in southern Ontario: A preliminary study.
AB  - The prevalence and patterns of antimicrobial susceptibility of fecal Escherichia
      coli, Salmonella spp., extended beta-lactamase producing E. coli (ESBL-E. coli),
      methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant
      Staphylococcus pseudintermedius (MRSP) were determined for healthy dogs (n = 188)
      and cats (n = 39) from veterinary hospitals in southern Ontario that had not had
      recent exposure to antimicrobials. The prevalence of antimicrobial resistance in
      E. coli was as follows: streptomycin (dogs - 17%, cats - 2%), ampicillin (dogs -
      13%, cats - 4%), cephalothin (dogs - 13%, cats - < 1%), and tetracycline (dogs -
      11%, cats - 2%). Eleven percent of dogs and 15% of cats had isolates that were
      resistant to at least 2 antimicrobials. Cephamycinase (CMY)-2 producing E. coli
      was cultured from 2 dogs. No Salmonella spp., ESBL-E. coli, MRSA, or MRSP
      isolates were recovered. The observed prevalence of resistance in commensal E.
      coli from this population was lower than that previously reported in companion
      animals, but a small percentage of dogs may be a reservoir for CMY-2 E. coli.

PMID- 20046604
TI  - Estrogen-induced myelotoxicity in dogs: A review.
AB  - Exogenous estrogens used for therapeutic purposes or endogenous estrogen sources
      such as functional Sertoli cell or ovarian granulosa cell tumors may cause bone
      marrow toxicity in dogs. The condition is characterized by hematologic
      abnormalities including thrombocytopenia, anemia, and leukocytosis or leukopenia.
      Despite intensive therapy with blood or platelet-rich transfusions, broad
      spectrum antibiotics, steroids, and bone marrow stimulants, prognosis is
      unfavorable. Due to the the risk of stimulating the development of uterine
      diseases and the potential for inducing aplastic anemia, estrogen use in dogs is
      best avoided where possible. This paper describes the causes of estrogen-induced
      myelotoxicity, the clinical presentation of the patients, the diagnosis, and the
      treatment options in the dog.

PMID- 20046605
TI  - The effect of foot-and-mouth disease (FMD) vaccination on virus transmission and
      the significance for the field.
AB  - Vaccination against foot-and-mouth disease (FMD) might be one of the control
      measures used during an FMD epidemic depending on the local epidemiological
      situation, the status of the country, and the opinion of policy makers. A sound
      decision on vaccination can be made only if there is sufficient scientific
      knowledge on the effectiveness of vaccination in eliminating the virus from the
      population. An important question is whether a single vaccination applied as an
      emergency vaccine can contribute to the control of an epidemic. This paper
      presents the results of transmission experiments on vaccine efficacy in groups of
      cattle, pigs, and sheep and concludes that vaccination seemed to be effective in
      cattle and sheep, but was less effective in pigs. The possible implications for
      application to field conditions are discussed.

PMID- 20046606
TI  - Use of radiographic measurements in the evaluation of dogs with medial patellar
      luxation.
AB  - This prospective study used radiographic techniques to evaluate the inclination,
      Norberg, quadriceps and femoral varus angles, and the patellar position in dogs
      with developmental medial patellar luxation. The study also compared these
      measurements pre- and post-operatively to determine how they were affected by
      surgical procedures. Eighteen dogs with unilateral or bilateral luxation were
      used, and 4 groups were established according to luxation grade. Except for the
      quadriceps angle, there was no difference among the groups preoperatively.
      Significant differences for the quadriceps angle were observed between Grades 1
      and 3, and between Grades 2 and 3. The Norberg and femoral varus angles and the
      patellar position showed no changes between pre- and postoperative groups.
      However, measurements of the preoperative quadriceps angle and postoperative
      inclination angle may be useful for evaluating dogs with grade-3 luxation.
      Further studies using other imaging techniques are required in dogs with severe
      grade-4 luxation due to the difficulty in obtaining a good radiographic position.

PMID- 20046607
TI  - Characteristics of six recent animal hoarding cases in Manitoba.
AB  - Six recent cases of animal hoarding in Manitoba were compared to the relevant
      literature. Cases were similar to previous reports in age and demographics of
      hoarders. Five cases involved small mammals and 1 case involved horses.
      Understanding this phenomenon would be enhanced by consistent investigative
      format and reporting and closer working relationships with public health.

PMID- 20046608
TI  - Detection, characterization, and control of bovine viral diarrhea virus infection
      in a large commercial dairy herd.
AB  - Detection, genetic characterization, and control of bovine viral diarrhea virus
      (BVDV) disease in a large commercial dairy herd is reported. Precolostral BVDV
      serum antibody was detected in 5.3% (12/226) of newborn calves before the test
      and removal of persistently infected (PI) animals and in 0.4% (2/450) of newborn
      calves after the removal of PI heifers.

PMID- 20046609
TI  - Ethics and euthanasia.

PMID- 20046610
TI  - Recessionary communication - A final note.

PMID- 20046611
TI  - Diagnosis and clinical signs of feline infectious peritonitis in the central
      nervous system.

PMID- 20046612
TI  - Sesamoid disease.

PMID- 20046613
TI  - Cyathostominosis in a horse from Saskatchewan.

PMID- 20046614
TI  - Re: "Upper Limb Neural Tension and Seated Slump Tests: The False Positive Rate
      Among Healthy Young Adults without Cervical or Lumbar Symptoms" Daves et al. J
      Man Manip Ther 2009;16:136-141.

PMID- 20046615
TI  - Author response.

PMID- 20046617
TI  - Systematic review of efficacy for manual lymphatic drainage techniques in sports
      medicine and rehabilitation: an evidence-based practice approach.
AB  - Manual therapists question integrating manual lymphatic drainage techniques
      (MLDTs) into conventional treatments for athletic injuries due to the scarcity of
      literature concerning musculoskeletal applications and established orthopaedic
      clinical practice guidelines. The purpose of this systematic review is to provide
      manual therapy clinicians with pertinent information regarding progression of
      MLDTs as well as to critique the evidence for efficacy of this method in sports
      medicine. We surveyed English-language publications from 1998 to 2008 by
      searching PubMed, PEDro, CINAHL, the Cochrane Library, and SPORTDiscus databases
      using the terms lymphatic system, lymph drainage, lymphatic therapy, manual lymph
      drainage, and lymphatic pump techniques. We selected articles investigating the
      effects of MLDTs on orthopaedic and athletic injury outcomes. Nine articles met
      inclusion criteria, of which 3 were randomized controlled trials (RCTs). We
      evaluated the 3 RCTs using a validity score (PEDro scale). Due to differences in
      experimental design, data could not be collapsed for meta-analysis. Animal model
      experiments reinforce theoretical principles for application of MLDTs. When
      combined with concomitant musculoskeletal therapy, pilot and case studies
      demonstrate MLDT effectiveness. The best evidence suggests that efficacy of MLDT
      in sports medicine and rehabilitation is specific to resolution of enzyme serum
      levels associated with acute skeletal muscle cell damage as well as reduction of
      edema following acute ankle joint sprain and radial wrist fracture. Currently,
      there is limited high-ranking evidence available. Well-designed RCTs assessing
      outcome variables following implementation of MLDTs in treating athletic injuries
      may provide conclusive evidence for establishing applicable clinical practice
      guidelines in sports medicine and rehabilitation.

PMID- 20046616
TI  - Correlation of digital palpation and transabdominal ultrasound for assessment of
      pelvic floor muscle contraction.
AB  - Pelvic floor muscle (PFM) dysfunction has been commonly associated with urinary
      disorders and lumbo-pelvic pain. Transabdominal (TA) ultrasound is currently used
      by physical therapists to assess PFM function. Controversy exists regarding the
      correlation between TA ultrasound measurement and vaginal palpation for
      assessment of PFM contraction, and this relationship has not yet been examined
      concurrently during the same contraction. The purpose of this study was to
      determine the correlation of digital palpation and TA ultrasound to assess PFM
      contraction when recorded 1) simultaneous to digital palpation during one
      contraction and 2) following digital palpation testing in another contraction. A
      descriptive correlational design was used to describe the relationship between
      variables. A total of 19 women (both asymptomatic women and those with
      incontinence or lumbo-pelvic pain) participated in the study. The modified Oxford
      scale was used to grade PFM contraction in digital palpation testing. The amount
      of bladder base movement on ultrasound was measured and considered as an
      indicator of PFM activity. Two trials were performed for TA ultrasound
      measurement: 1) simultaneous to digital palpation during one contraction, and 2)
      following digital palpation testing in another contraction. Spearman's
      correlation coefficient was used for analysis. There was a significant
      correlation between digital palpation and TA ultrasound for PFM assessment when
      measured simultaneously in one contraction (rho=0.62, p=0.01) and separately in a
      different contraction (rho=0.52, p=0.02), with a stronger correlation found in
      simultaneous testing. In conclusion, digital palpation and TA ultrasound
      measurement are significantly correlated and measure comparable parameters in
      evaluation of PFM contraction.

PMID- 20046618
TI  - So Close and Yet so Far-Growth and Progress in the Accessory Motion Testing
      Literature.

PMID- 20046619
TI  - The Reliability of Maitland's Irritability Judgments in Patients with Low Back
      Pain.
AB  - Maitland's construct of musculoskeletal pain irritability is widely used by
      physical therapists but has not been defined to the extent that its measurement
      properties can be tested. The purpose of this study was to examine the inter
      rater reliability of physical therapists' irritability judgments during
      application to patients with low back pain (LBP). Eighty patients with LBP
      received two consecutive examinations at their initial clinic visit by two
      physical therapists. Patients reported pain location and intensity prior to each
      evaluation. Therapists judged subjects' LBP as irritable or non-irritable. Inter
      rater agreement of physical therapist irritability judgments was moderate (kappa
      = 0.44, prevalence-adjusted kappa = 0.50). This level of reliability of
      therapists' LBP irritability judgments may be improved upon by development of an
      operational definition of pain irritability. Further research is needed to
      identify measures appropriate for inclusion in an operational definition of pain
      irritability and to assess the value of making pain irritability judgments in
      evidence-based physical therapy practice.

PMID- 20046620
TI  - Publishing a scientific manuscript on manual therapy.
AB  - Publication in peer-reviewed journals is the way to introduce new information
      that has clinical implications. However, clinicians may be reluctant to embark on
      the publication process because of lack of confidence or uncertainty about the
      process. The aim of this paper is to summarize the requirements of that process
      and to provide tips for successful publication to encourage potential clinical
      authors of manual therapy articles. In general, articles should contribute
      knowledge, corroborate or contradict previous knowledge, or summarize existing
      knowledge. Articles should be clearly structured, with abstract, introduction,
      methods, discussion, conclusion, and references; and often include tables and
      figures. The content of each of these sections is described. The use of
      standardized checklists is encouraged and the format should adhere to each
      journal's author guidelines. Submission is electronic and typically first the
      editor or deputy editor reviews for suitability, adherence to journal format, and
      quality of writing. If deemed suitable, the article is then sent out for blinded
      review by two reviewers with expertise in that area. Review typically takes 6-8
      weeks, and all communication is via the editor. A decision is made then to either
      accept, accept with amendments to be made, reject but with advice to resubmit, or
      reject outright. In any re-submissions, the review teams' comments should be
      diligently addressed, either making the recommended changes or justifying why
      they have not been adopted. Common reasons for rejection of articles are given.
      Finally, the authors provide some tips for publication to help readers with
      successful submission of articles.

PMID- 20046621
TI  - Correlation of magnetic resonance imaging findings and reported symptoms in
      patients with chronic cervical dysfunction.
AB  - Information gathered from the patient history, physical examination, and advanced
      testing augments the decision-making process and is proposed to improve the
      probability of diagnostic and prognostic accuracy. However, these findings may
      provide inconsistent results and can lead to errors in decision-making. The
      purpose of this study was to examine the relationship between common clinical
      complaints and specific findings on magnetic resonance imaging (MRI) in patients
      with chronic neck dysfunction. Forty-five English-speaking participants (25
      female), with mean age of 52 (SD = 13.4), were evaluated by a neurosurgeon for
      complaints of symptoms related to the cervical spine. All participants answered a
      subjective questionnaire and received an MRI of the cervical spine. Cramer's V
      nominal correlation was performed to explore the relationship between the
      targeted variables. The correlation matrix calculations captured three
      significant findings. Evidence of spinal cord compression was significantly
      correlated to 1) anteroposterior canal diameter of less than or equal to 9 mm (r
      = .31; p<0.05) and 2) diminished subarachnoid fluid around the cord (r = .48;
      p<0.01). Report of loss of dexterity was significantly correlated with 3) report
      of lower extremity clumsiness (r = .33; p<0.05). In this study, no definitive
      relationships were found between the clinical complaints of neck pain, hand
      function, or clumsiness and specific MRI findings of spinal cord compression.
      Further research is needed to investigate the diagnostic utility of subjective
      complaints and their association with advanced testing.

PMID- 20046622
TI  - Repeated Applications of Thoracic Spine Thrust Manipulation do not Lead to
      Tolerance in Patients Presenting with Acute Mechanical Neck Pain: A Secondary
      Analysis.
AB  - It has been demonstrated that patients receiving mobilization techniques do not
      exhibit tolerance to repeated applications. However, this phenomenon has not been
      investigated for thoracic manipulation. Our aim was to determine if patients
      receiving thoracic thrust manipulation exhibit tolerance to repeated applications
      in acute mechanical neck pain. Forty-five patients were randomly assigned to two
      groups. The control group received electro- and thermotherapy for 5 sessions, and
      the experimental group received the same program and also received a thoracic
      thrust manipulation once a week for 3 consecutive weeks. Outcome measures
      included neck pain and cervical mobility. Within-session change scores for pain
      and mobility during treatment sessions #1, 3, and 5 were examined with a one-way
      repeated measured ANOVA. A 2-way ANOVA with session as within-subject variable
      and group as between-subject variable was used to compare change scores for each
      visit between groups to ascertain if there were significant between-group
      differences in within-session changes for the experimental versus the control
      group. The ANOVA showed that for either group the 3 within-session change scores
      were not significantly different (P > 0.1). The 2-way ANOVA revealed significant
      differences between groups for both pain and neck mobility in within-session
      change scores (all, P < 0.001). Change scores in each session were superior in
      the experimental group as compared to those in the control group. The results
      suggest that patients receiving thoracic manipulation do not exhibit tolerance to
      repeated applications with regard to pain and mobility measures in acute
      mechanical neck pain. Further studies should investigate the dose-response
      relationship of thoracic thrust manipulation in this population.

PMID- 20046623
TI  - Global rating of change scales: a review of strengths and weaknesses and
      considerations for design.
AB  - Most clinicians ask their patients to rate whether their health condition has
      improved or deteriorated over time and then use this information to guide
      management decisions. Many studies also use patient-rated change as an outcome
      measure to determine the efficacy of a particular treatment. Global rating of
      change (GRC) scales provide a method of obtaining this information in a manner
      that is quick, flexible, and efficient. As with any outcome measure, however,
      meaningful interpretation of results can only be undertaken with due
      consideration of the clinimetric properties, strengths, and weaknesses of the
      instrument. The purpose of this article is to summarize this information to
      assist appropriate interpretation of the GRC results and to provide evidence
      informed advice to guide design and administration of GRC scales. These
      considerations are relevant and applicable to the use of GRC scales both in the
      clinic and in research.

PMID- 20046624
TI  - Cyriax physiotherapy versus phonophoresis with supervised exercise in subjects
      with lateral epicondylalgia: a randomized clinical trial.
AB  - Cyriax and Cyriax advocated the use of deep transverse friction massage in
      combination with Mill's manipulation in treating lateral epicondylalgia. Evidence
      comparing this approach with other physical therapies is lacking. The purpose of
      this randomized clinical trial was to compare the effectiveness of deep
      transverse friction massage with Mill's manipulation versus phonophoresis with
      supervised exercise in managing lateral epicondylalgia. Sixty patients age 30-60,
      presenting with the teno-periosteal variety of lateral epicondylalgia with
      symptom duration greater than one month, were randomized into two groups. The
      control group received phonophoresis with diclofenac gel over the area of the
      lateral epicondyle for 5 minutes combined with supervised exercise. The
      experimental group received 10 minutes of deep transverse friction massage
      followed by a single application of Mill's manipulation. Both groups received
      treatment 3 times per week for 4 weeks. Outcomes of interest included pain via
      visual analog scale (VAS), pain-free grip strength, and functional status
      measured with the Tennis Elbow Function Scale. Data were analyzed using a one-way
      ANOVA. Whereas both groups improved significantly from the initiation of
      treatment, a between-group comparison revealed significantly greater (p<0.05)
      improvements regarding pain, pain-free grip, and functional status for the
      experimental group compared to the control group. The results of this study
      demonstrate that Cyriax physiotherapy is a superior treatment approach compared
      to phonophoresis and exercise in managing lateral epicondylalgia.

PMID- 20046625
TI  - Use of a questionnaire to predict von Willebrand disease status and characterize
      hemorrhagic signs in a population of dogs and evaluation of a diagnostic profile
      to predict risk of bleeding.
AB  - The objective of this study was to use a questionnaire 1) for characterization of
      hemorrhagic signs; 2) to assess its value as a predictor of von Willebrand
      Disease (vWD) status; and 3) for evaluation of the vWD diagnostic profile
      [platelet function analysis using the PFA-100, Collagen binding assay (vWF:CBA),
      and vWF antigen ELISA (vWF:Ag)], partial thromboplastin time (PTT) and Factor
      VIII activity (FVIII) as predictors of hemorrhagic risk. von Willebrand factor
      (vWF) concentration and function was assessed for each of the 165 canine
      participants using the vWD diagnostic profile. Hemorrhagic signs for each dog
      were obtained using a standardized questionnaire. Questionnaires were scored
      according to a previously prepared scoring key. Of the 165 dogs in the study,
      43.6% had a low vWF concentration, with only 48.6% of dogs in this group having
      reports of hemorrhagic signs. Oral bleeding was the most commonly reported sign.
      The questionnaire had a sensitivity of 48.6% and a specificity of 78.5% for the
      prediction of vWD status. Using the Spearman correlation coefficient, a
      statistical association was found between the questionnaire and the vWD
      diagnostic profile components. However, this could not be translated into an
      ability to predict hemorrhage. The questionnaire allowed characterization of
      hemorrhagic signs in a large population of dogs over a range of vWF:Ag
      concentrations, and demonstrated that the vWD diagnostic profile was unsuccessful
      in the prediction of hemorrhagic risk. Although the sensitivity was insufficient
      for a screening tool, the questionnaire did have some discriminatory power in the
      prediction of vWD status.

PMID- 20046626
TI  - Evaluation of laboratory methods to improve characterization of dogs with von
      Willebrand disease.
AB  - The objective of the study was to investigate the value of additional tests
      [platelet count, partial thromboplastin time (PTT), platelet function analysis
      using the PFA-100, Collagen binding assay (vWF:CBA), and Factor VIII activity],
      for use in conjunction with the von Willebrand factor antigen enzyme-linked
      immunosorbent assay (ELISA), as part of a newly developed diagnostic profile for
      improved characterization of patients with von Willebrand disease (vWD). The
      study population included 183 clinically healthy canines ranging in vWF:Ag
      concentration from 1% to 125%. The Asserachrom vWF:Ag ELISA assay was used as an
      external control for the determination of vWD status. Degree of association
      between the additional tests and vWF concentration was evaluated, and
      associations between the additional tests were also assessed, including their
      ability to distinguish dogs with vWD from those without vWD. In addition, a
      reference interval was determined for the PFA-100 platelet function analyzer.
      Strong associations were found between the PFA-100, vWF:CBA, and Asserachrom
      vWF:Ag assay, and a significant association was found between the PFA-100 and
      vWF:CBA. An association was detected between Factor VIII activity and the
      Asserachrom vWF:Ag assay, the vWF:CBA and the PFA-100; however, a corresponding
      pattern was not visually apparent in the raw data, making the association
      clinically irrelevant. The association between the platelet count and the PTT
      with the other additional tests was negligible. Based on our results, the vWF:CBA
      and PFA-100 would be valuable assets, in conjunction with a vWF:Ag assay, in a
      canine vWD diagnostic profile to further characterize patients with this disease.

PMID- 20046627
TI  - Antagonistic effects of atipamezole and yohimbine on medetomidine-induced
      diuresis in healthy dogs.
AB  - This study aimed to investigate and compare the antagonistic effects of
      atipamezole and yohimbine on medetomidine-induced diuresis in healthy dogs. Five
      dogs were used repeatedly in each of 8 groups. One group was not medicated. Dogs
      in the other groups received 20 microg/kg of medetomidine intramuscularly and,
      0.5 h later, saline (as the control injection), 50, 100, or 300 microg/kg of
      atipamezole, or 50, 100, or 300 microg/kg of yohimbine intramuscularly. Urine and
      blood samples were taken 11 times over 24 h for measurement of the following:
      urine volume, specific gravity, and creatinine concentration; urine and plasma
      osmolality; urine and plasma concentrations of electrolytes and arginine
      vasopressin (AVP); and the plasma concentration of atrial natriuretic peptide
      (ANP). Both atipamezole and yohimbine antagonized the diuretic effect of
      medetomidine, inhibiting medetomidine-induced decreases in urine specific
      gravity, osmolality, and concentrations of creatinine, sodium, potassium,
      chloride, and AVP and reversing both the medetomidine-induced increase in plasma
      concentrations of sodium, potassium, and chloride and the medetomidine-induced
      decrease in the plasma AVP concentration. Atipamezole significantly stimulated
      ANP release. The antidiuretic action of yohimbine was more potent than that of
      atipamezole but was not dose-dependent, in contrast to the action of atipamezole.
      The effects of these drugs may not be due only to actions mediated by alpha(2)
      adrenoceptors.

PMID- 20046628
TI  - Effect of post-insemination progesterone supplementation on pregnancy rate in
      dairy cows.
AB  - Progesterone plays an important role in maintenance of pregnancy. It is
      hypothesized that insufficient progesterone early in pregnancy may result in
      embryonic loss, and that supplemental progesterone would decrease pregnancy loss
      in dairy cows. In Experiment 1, 84 cows and 16 heifers from a single dairy
      operation were selected randomly. Within each age category, controlled internal
      drug release (CIDR) devices were inserted into the vagina of every other female
      on Day 4 post-insemination and removed on Day 18 post-insemination. Transrectal
      ultrasonography was performed to determine pregnancy at 4 time periods [days 30
      to 37 (week 5), days 44 to 51 (week 7), days 58 to 65 (week 9), and days 86 to 93
      (week 13)]. Progesterone supplementation had no effect on pregnancy rate. In
      Experiment 2, there were no differences in progesterone concentrations between
      cows that did and did not receive a CIDR. Further, cows receiving CIDR devices
      did not have an increase in circulating progesterone concentrations 30 min or 1 h
      after CIDR insertion. It appears that progesterone supplementation does not
      increase circulating levels of progesterone in the early pregnant lactating dairy
      cow. Alterative methods to influence progesterone concentrations and/or early
      embryonic loss need to be investigated.

PMID- 20046629
TI  - Prevalence and risk factor investigation of Campylobacter species in beef cattle
      feces from seven large commercial feedlots in Alberta, Canada.
AB  - This fecal prevalence study targeted cattle from 7 large (10,000 to > 40,000
      head) commercial feedlots in Alberta as a means of establishing Campylobacter
      levels in cattle just prior to animals entering the food chain. Overall, 87% [95%
      confidence interval (CI) = 86-88] of 2776 fresh pen-floor fecal samples were
      culture positive for Campylobacter species, with prevalences ranging from 76% to
      95% among the 7 feedlots. Campylobacter spp. prevalence was 88% (95% CI = 86-90)
      in the summer (n = 1376) and 86% (95% CI = 85-88) in the winter (n = 1400). In
      addition, 69% (95% CI = 66-71) of 1486 Campylobacter spp. positive samples were
      identified as Campylobacter jejuni using hippurate hydrolysis testing. Of those,
      64% (95% CI = 58-70) of 277 and 70% (95% CI = 67-72) of 1209 Campylobacter
      isolates were identified as C. jejuni in winter and summer, respectively. After
      accounting for clustering within pen and feedlot, feedlot size and the number of
      days on feed were associated with Campylobacter spp. isolation rates. The high
      isolation rates of Campylobacter spp. and C. jejuni in feedlot cattle feces in
      this study suggest a potential role for feedlot cattle in the complex
      epidemiology of campylobacters in Alberta.

PMID- 20046630
TI  - Prevalence of bovine viral diarrhea virus (BVDV) in persistently infected cattle
      and BVDV subtypes in affected cattle in beef herds in south central United
      States.
AB  - The prevalence of bovine viral diarrhea virus (BVDV) in persistently infected
      (PI) cattle in beef breeding herds was determined using 30 herds with 4530
      calves. The samples were collected by ear notches and tested for BVDV antigens
      using immunohistochemistry (IHC) and antigen capture enzyme-linked immunosorbent
      assay (ACE). Animals with initial positives on both IHC and ACE were sampled
      again using both tests and serums were collected for viral propagation and
      sequencing of a viral genomic region, 5'-untranslated region (5'-UTR) for viral
      subtyping. Samples were also collected from the dams of PI calves. There were 25
      PI calves from 4530 samples (0.55%) and these PI calves were from 5 of the 30
      herds (16.7%). Two herds had multiple PI calves and 3 herds had only 1 PI calf.
      Only 1 of the 25 dams with a PI calf was also PI (4.0%). The subtype of all the
      PI isolates was BVDV1b. Histories of the ranches indicated 23 out of 30 had herd
      additions of untested breeding females. Twenty-four of the 30 herds had adult
      cowherd vaccinations against BVDV, primarily using killed BVDV vaccines at
      pregnancy examination.

PMID- 20046631
TI  - Fetal protection against bovine viral diarrhea virus types 1 and 2 after the use
      of a modified-live virus vaccine.
AB  - The objective of this study was to demonstrate the efficacy of a modified-live
      virus (MLV) vaccine in protecting fetuses from infection with type 1 or type 2
      Bovine viral diarrhea virus (BVDV) when pregnant heifers were challenged at
      approximately 170 d of gestation with noncytopathic field isolates. The 83
      pregnant heifers had been bred naturally 4 wk after vaccination. Fetuses were
      collected 60 d after BVDV type 2 challenge, and newborn calves were collected
      before colostrum intake after BVDV type 1 challenge. Protection was determined by
      measuring the serum neutralizing (SN) antibody response in the fetus or calf and
      by virus isolation from thymus, lung, spleen, and kidney tissue samples. There
      was a measurable SN antibody response to BVDV in all the fetuses and calves of
      the control heifers, which had received a placebo vaccine. However, only 4 of 22
      calves and 7 of the 28 fetuses of the MLV-vaccinated heifers demonstrated SN
      antibody after BVDV challenge. Type 1 BVDV was isolated from tissue samples of 5
      of the 12 calves of control heifers and none of 22 calves of the MLV-vaccinated
      heifers challenged with type 1 BVDV. Type 2 BVDV was isolated from tissue samples
      of 17 of the 18 fetuses of the control heifers and 2 of the 28 fetuses of the MLV
      vaccinated heifers challenged with type 2 BVDV. The results of this study
      demonstrate that the MLV vaccine reduces the fetal infection rate by at least 82%
      for BVDV type 1 and by 75% for BVDV type 2 when heifers are exposed to highly
      fetotrophic BVDV at 170 d of gestation.

PMID- 20046632
TI  - Further assessment of fomites and personnel as vehicles for the mechanical
      transport and transmission of porcine reproductive and respiratory syndrome
      virus.
AB  - This study re-evaluated the role of fomites and personnel in the mechanical
      transport and transmission of porcine reproductive and respiratory syndrome virus
      (PRRSV) between pig populations. Swabs were collected from hands, boots,
      coveralls, and other fomites following contact with infected pigs and compared
      with identical samples collected in the absence of PRRSV exposure. Naive pigs
      were provided contact with contaminated fomites/personnel and blood tested
      periodically post-exposure [positive exposure population (PEP)] and compared with
      populations that did not gain exposure via these routes [negative exposure
      population (NEP)]. The majority of swab samples from hands, coveralls, and boots
      from personnel and fomite samples (cable snare and bleeding equipment) following
      contact with the PRRSV-infected Source Population. Transmission of PRRSV to the
      PEP was observed (7/7) cases but not in the NEP. In conclusion, under the proper
      conditions, transport and transmission of PRRSV by fomites and personnel may
      occur between swine populations in the absence of intervention.

PMID- 20046633
TI  - Infection dynamics and clinical manifestations following experimental inoculation
      of gilts at 90 days of gestation with a low dose of porcine reproductive and
      respiratory syndrome virus.
AB  - Understanding the dynamics of porcine reproductive and respiratory syndrome virus
      (PRRSV) vertical transmission is important to enhance the accuracy of monitoring
      protocols for endemically infected breeding herds. The objectives of this study
      were to determine the prevalence of PRRSV within infected litters, to quantify
      viremia, and to identify specific attributes of infected individuals. Eight gilts
      were intramuscularly inoculated with 10(1) TCID(50) of a mildly virulent PRRSV
      strain (MN-30100) at 90 d of gestation. All inoculated gilts transmitted the
      virus in utero. The proportion of PRRSV PCR-positive piglets and the level of
      viremia in the piglets were higher at 4 d of age than at birth or at weaning. No
      specific attributes were associated with PRRSV infection in the piglets. This is
      the first report, that we are aware of, documenting the efficient in utero
      transmission of an extremely low dose of a mildly virulent strain of PRRSV. The
      results support the sampling of piglets late during lactation as a tool to
      monitor PRRSV shedding from sow-herds.

PMID- 20046634
TI  - Prevalence of infection with porcine circovirus-2 (PCV-2) and porcine
      reproductive and respiratory syndrome virus (PRRSV) in an integrated swine
      production system experiencing postweaning multisystemic wasting syndrome.
AB  - The objective of this study was to evaluate the prevalence of infection with
      porcine circovirus-2 (PCV-2) and porcine reproductive and respiratory syndrome
      virus (PRRSV) through a longitudinal study in an integrated swine production
      system (7 farms) experiencing postweaning multisystemic wasting syndrome (PMWS).
      Risk factors for PCV-2 infection and for PCV-2 and PRRSV coinfection were also
      evaluated. Fifteen sows from each herd and 4 non-cross-fostered piglets from each
      sow were randomly selected at farrowing and ear-tagged at birth. Serum samples
      were analyzed for antibodies to PCV-2 and for detection of the PCV-2 and PRRSV
      genomes. Statistical analyses involved 2 approaches. The 1st approach
      characterized the dynamics of PCV-2 infection and their relationship with PRRSV
      infection. The 2nd approach analyzed the probability of being infected by PCV-2
      or by both PCV-2 and PRRSV through a generalized linear mixed model incorporating
      sow and farm characteristics. At the 1st sampling time (1 wk of age), there was a
      significant relationship between sow PCV-2 infection and piglet PCV-2 infection
      (P < 0.0001). The risk of PCV-2 and PRRSV coinfection was 1.85 times greater in
      piglets from a sow with low titers of PCV-2 antibodies than in piglets from sows
      with medium to high titers (P = 0.03) and was 2.54, 2.40, and 2.02 times greater,
      respectively, in piglets from primiparous sows, PCV-2-infected sows, and farms in
      an area of high pig density than in piglets from sows of higher parity (P =
      0.004), noninfected sows (P = 0.04), and farms in a low-density area (P = 0.09).

PMID- 20046635
TI  - Evaluation of porcine reproductive and respiratory syndrome virus replication in
      laboratory rodents.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is a major cause of
      economic losses in the swine industry. The disease is widespread worldwide, and
      so PRRSV-negative pigs are often difficult to find for the study of PRRSV in
      vivo. To determine if a small animal model could be developed for PRRSV, 3
      strains of laboratory rodent were examined for their susceptibility to the virus.
      No virus replication was detected in BALB/c or SCID (severe combined
      immunodeficiency) mice after intraperitoneal inoculation. Moderate replication of
      PRRSV was detected in primary cotton rat lung cell cultures, but no viral
      replication was detected following intranasal or intraperitoneal inoculation.
      Following intratracheal inoculation, viral transcripts were detected in the lungs
      of cotton rats, but only for 1 day. This study indicates that PRRSV replication
      in common laboratory rodent species is inefficient, and suggests that a rodent
      model for this virus is not appropriate.

PMID- 20046637
TI  - Marking the onset of oxidative stress: biomarkers and novel strategies.

PMID- 20046638
TI  - Hypoxia mediated release of endothelial microparticles and increased association
      of S100A12 with circulating neutrophils.
AB  - Microparticles are released from the endothelium under normal homeostatic
      conditions and have been shown elevated in disease states, most notably those
      characterised by endothelial dysfunction. The endothelium is sensitive to
      oxidative stress/status and vascular cell adhesion molecule-1 (VCAM-1) expression
      is upregulated upon activated endothelium, furthermore the presence of VCAM-1 on
      microparticles is known. S100A12, a calcium binding protein part of the S100
      family, is shown to be present on circulating leukocytes and is thought a
      sensitive marker to local inflammatory process, which may be driven by oxidative
      stress. Eight healthy males were subjected to breathing hypoxic air (15% O(2),
      approximately equivalent to 3000 metres altitude) for 80 minutes in a temperature
      controlled laboratory and venous blood samples were processed immediately for
      VCAM-1 microparticles (VCAM-1 MP) and S100A12 association with leukocytes by flow
      cytometry. A pre-hypoxic blood sample was used for comparison. Both VCAM-1 MP and
      S100A12 association with neutrophils were significantly elevated post hypoxic
      breathing later declining to levels observed in the pre-test samples. A similar
      trend was observed in both cases and a correlation may exist between these two
      markers in response to hypoxia. These data offer evidence using novel markers of
      endothelial and circulating blood responses to hypoxia.

PMID- 20046639
TI  - Endothelial nitric oxide synthase expression is progressively increased in
      primary cerebral microvascular endothelial cells during hyperbaric oxygen
      exposure.
AB  - Exposure to hyperbaric oxygen (HBO) can lead to seizures. Many studies have
      demonstrated that there exist a very close relationship between the alteration of
      cerebral blood flow (CBF) and the onset of seizures. Nitric oxide (NO) may play a
      key role in the change of CBF during exposure, and modulation of endothelial
      nitric oxide synthase (eNOS)-derived NO by HBO is responsible for early
      vasoconstriction, whereas late HBO-induced vasodilation depends upon a large
      amount of NO from both eNOS and neuronal nitric oxide synthase (nNOS). To
      investigate the effect of HBO on the activity and expression of eNOS in cerebral
      microvascular endothelial cells (CMEC) in vitro, primarily cultured CMEC from
      neonatal rats were exposed to oxygen at 500 kPa [5 atmosphere absolute (ATA)] for
      10, 20, 30, 60 and 120 minutes (min), then eNOS activity, protein and mRNA
      contents in cells were detected. Our results showed that immediately after
      exposure, 30, 60 and 120 min HBO exposures did not alter NOS activity. When
      detected no matter immediately or six hours (h) after exposure, these exposures
      also did not alter eNOS protein and mRNA levels. However, when detected 24 h
      after exposure, 30, 60 and 120 min exposures upregulated eNOS protein content by
      39%, 60% and 40% respectively. 10 and 20 min exposures upregulated eNOS mRNA
      content by about 15%, while 30, 60 and 120 min exposures upregulated it by about
      20-30%. The increased eNOS protein and mRNA contents at 24 h after exposure may
      reflect new protein synthesis for eNOS. Our studies showed that with the exposing
      protocols we used, HBO did induce eNOS expression increase in CMEC. However,
      compared with the decrease of CBF in vivo, which occurred in a relative short
      time after rat was exposed to HBO above 4 ATA, the responses of eNOS in CMEC in
      vitro were a little slow. Thus we considered that for the vasodilation in the
      late period of HBO exposure before seizure, the effect of NO produced by eNOS was
      limited.

PMID- 20046640
TI  - Antioxidative defense enzymes in placenta protect placenta and fetus in inherited
      thrombophilia from hydrogen peroxide.
AB  - Our aim was to investigate the activities of antioxidative defense enzymes in the
      placenta, fetal blood and amnion fluid in inherited thrombophilia. Thrombophilia
      was associated with nearly threefold increase of activity (p < 0.001) of the
      placental catalase (81.1 +/- 20.6 U/mg of proteins in controls and 270.0 +/- 69.9
      U/mg in thrombophilic subjects), glutathione (GSH) peroxidase (C: 20.2 +/- 10.1
      U/mg; T: 60.0 +/- 15.5 U/mg), and GSH reductase (C: 28.9 +/- 5.6 U/mg; T: 72.7 +/
      23.0 U/mg). The placental activities of superoxide dismutating enzymes--MnSOD
      and CuZnSOD, did not differ in controls and thrombophilia. Likewise, the
      activities of catalase and SOD in the fetal blood, and the level of ascorbyl
      radical which represents a marker of oxidative status of amniotic fluid, were
      similar in controls and thrombophilic subjects. From this we concluded that in
      thrombophilia, placental tissue is exposed to H(2)O(2)-mediated oxidative stress,
      which could be initiated by pro-thrombic conditions in maternal blood. Increased
      activity of placental H(2)O(2)-removing enzymes protects fetus and mother during
      pregnancy, but may increase the risk of postpartum thrombosis.

PMID- 20046641
TI  - Systemic oxidative stress is increased to a greater degree in young, obese women
      following consumption of a high fat meal.
AB  - High fat meals induce oxidative stress, which is associated with the pathogenesis
      of disease. Obese individuals have elevated resting biomarkers of oxidative
      stress compared to non-obese. We compared blood oxidative stress biomarkers in
      obese (n = 14; 30 +/- 2 years; BMI 35 +/- 1 kg x m(-2)) and non-obese (n = 16; 24
      +/- 2 years; BMI 23 +/- 1 kg x m(-2)) women, in response to a high fat meal.
      Blood samples were collected pre-meal (fasted), and at 1, 2, 4 and 6 hours post
      meal, and assayed for trolox equivalent antioxidant capacity (TEAC), xanthine
      oxidase activity (XO), hydrogen peroxide (H(2)O(2)), malondialdehyde (MDA),
      triglycerides (TAG), and glucose. An obesity status effect was noted for all
      variables (p < 0.001; MDA p = 0.05), with obese women having higher values than
      non-obese, except for TEAC, for which values were lower. Time main effects were
      noted for all variables (p <= 0.01) except for TEAC and glucose, with XO,
      H(2)O(2), MDA and TAG increasing following feeding with a peak response at the
      four or six hour post feeding time point. While values tended to decline by six
      hours post feeding in the non-obese women (agreeing with previous studies), they
      were maintained (MDA) or continued to increase (XO, H(2)O(2) and TAG) in the
      obese women. While no interaction effects were noted (p > 0.05), contrasts
      revealed greater values in obese compared to non-obese women for XO, H(2)O(2),
      MDA, TAG and glucose, and lower values for TEAC at times from 1-6 hours post
      feeding (p <= 0.03). We conclude that young, obese women experience a similar
      pattern of increase in blood oxidative stress biomarkers in response to a high
      fat meal, as compared to non-obese women. However, the overall oxidative stress
      is greater in obese women, and values appear to remain elevated for longer
      periods of time post feeding. These data provide insight into another potential
      mechanism related to obesity-mediated morbidity.

PMID- 20046642
TI  - Metallothionein induction reduces caspase-3 activity and TNFalpha levels with
      preservation of cognitive function and intact hippocampal neurons in carmustine
      treated rats.
AB  - Hippocampal integrity is essential for cognitive functions. On the other hand,
      induction of metallothionein (MT) by ZnSO(4) and its role in neuroprotection has
      been documented. The present study aimed to explore the effect of MT induction on
      carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of
      60 male Wistar albino rats were randomly divided into four groups (15/group): The
      control group injected with single doses of normal saline (i.c.v) followed 24 h
      later by BCNU solvent (i.v). The second group administered ZnSO(4) (0.1
      micromol/10 microl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24
      h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with
      normal saline (i.c.v). Fourth group received a single dose of ZnSO(4) (0.1
      micromol/10 microl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24
      h. The obtained data revealed that BCNU administration resulted in deterioration
      of learning and short-term memory (STM), as measured by using radial arm water
      maze, accompanied with decreased hippocampal glutathione reductase (GR) activity
      and reduced glutathione (GSH) content. Also, BCNU administration increased serum
      tumor necrosis factor-alpha (TNFalpha), hippocampal MT and malondialdehyde (MDA)
      contents as well as caspase-3 activity in addition to histological alterations.
      ZnSO(4) pretreatment counteracted BCNU-induced inhibition of GR and depletion of
      GSH and resulted in significant reduction in the levels of MDA and TNFalpha as
      well as the activity of caspase-3. The histological features were improved in
      hippocampus of rats treated with ZnSO(4) + BCNU compared to only BCNU-treated
      animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as
      it prevented GR inhibition and GSH depletion and counteracted the increased
      levels of TNFalpha, MDA and caspase-3 activity with subsequent preservation of
      cognition.

PMID- 20046643
TI  - Oxidative stress induction of DJ-1 protein in reactive astrocytes scavenges free
      radicals and reduces cell injury.
AB  - Astrocytes, one of the predominant types of glial cells, function as both
      supportive and metabolic cells for the brain. Under cerebral ischemia/reperfusion
      induced oxidative conditions, astrocytes accumulate and activate in the ischemic
      region. DJ-1 has recently been shown to be a sensor of oxidative stress in living
      cells. However, the function of astrocytic DJ-1 is still unknown. In the present
      study, to clarify the effect of astrocytic DJ-1 protein under massive oxidative
      insult, we used a focal ischemic rat model that had been subjected to middle
      cerebral artery occlusion (MCAO) and reperfusion. We then investigated changes in
      the distribution of DJ-1 in astrocytes, DJ-1 release from cultured astrocytes,
      and the effects of recombinant DJ-1 protein on hydrogen peroxide (H(2)O(2))
      induced death in normal and DJ-1-knockdown SH-SY5Y cells and on in vitro
      scavenging of hydroxyl radicals ((*)OH) by electron spin resonance spectrometry.
      At 24 h after 2-h MCAO and reperfusion, an infarct lesion was markedly observed
      using magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride
      staining. In addition, reactive astrocytes enhanced DJ-1 expression in the
      penumbral zone of the ischemic core and that DJ-1 protein was extracellularly
      released from astrocytes by H2O2 in in vitro primary cultures. Although DJ-1
      knockdown SH-SY5Y cells were markedly vulnerable to oxidative stress, treatment
      with glutathione S-transferase-tagged recombinant human DJ-1 protein (GST-DJ-1)
      significantly inhibited H(2)O(2)-induced cell death. In addition, GST-DJ-1
      protein directly scavenged (*)OH. These results suggest that oxidative stress
      induces the release of astrocytic DJ-1 protein, which may contribute to astrocyte
      mediated neuroprotection.

PMID- 20046646
TI  - The increasing incidence of diabetes in the 21st century.

PMID- 20046645
TI  - Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic
      activity through potential GABA receptors in the nervous system without
      significant free radical generation.
AB  - Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing
      agent and also in research. Attention has been centered mainly on receptor
      binding and electrochemistry in the central nervous system which are briefly
      addressed herein. A novel integrated approach to mode of action is presented. The
      pathways to be discussed involve basicity, reduction potential, electrostatics,
      cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics,
      structure activity relationships (SAR) and side effects. The highly conjugated
      pyridinium salt formed by protonation of the amidine moiety is proposed to be the
      active form acting as an ET agent. Extrapolation of reduction potentials for
      related compounds supports the premise that zolpidem may act as an ET species in
      vivo. From recent literature reports, electrostatics is believed to play a
      significant role in drug action. The pyridinium cation displays molecular
      electrostatic potential which may well play a role energetically or as a bridging
      mechanism. An SAR analysis points to analogy with other physiologically active
      xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium
      category. Inactivity of metabolites indicates that the parent is the active form
      of zolpidem. Absence of reactive oxygen species and oxidative stress is in line
      with minor side effects. In contrast, generally, the prior literature contains
      essentially no discussion of these fundamental biochemical relationships.
      Pharmacodynamics may play an important role. Concerning behavior at the blood
      brain barrier, useful insight can be gained from investigations of the related
      cationic anesthetics that are structurally related to acetyl choline. Evidently,
      the neutral form of the drug penetrates the neuronal membrane, with the salt form
      operating at the receptor. The pathways of zolpidem have several clinical
      implications since the agent affects sedation, electroencephalographic activity,
      oxidative metabolites and receptors in the central nervous system. The drug acts
      at the GABA(A) receptor benzodiazepine site, displaying high and intermediate
      affinities to various receptor regions. Structural features for tight binding
      were determined. The sedative and anticonvulsant activities are due to its action
      on the alpha-1-GABA(A) receptors. One of the common adverse responses to zolpidem
      is hallucinations. Proposed mechanisms comprise changes in the GABA(A) receptor,
      pharmacodynamic interactions involving serotonin and neuronal-weak photon
      emission processes entailing redox phenomena. Reports cite cases of abuse with
      cravings based on anxiolytic and stimulating actions. It is important to
      recognize that insight concerning processes at the fundamental, molecular level
      can translate into beneficial results involving both positive and adverse side
      effects. In order for this to occur, interdisciplinary interaction is necessary.
      Suggestions are made for future research aimed at testing the various hypotheses.

PMID- 20046644
TI  - Oxidative stress and antioxidant defense mechanisms linked to exercise during
      cardiopulmonary and metabolic disorders.
AB  - Oxidative stress has been implicated in the pathophysiology of multiple human
      diseases, in addition to the aging process. Although various stimuli exist, acute
      exercise is known to induce a transient increase in reactive oxygen and nitrogen
      species (RONS), evident by several reports of increased oxidative damage
      following acute bouts of aerobic and anaerobic exercise. Although the results are
      somewhat mixed and appear disease dependent, individuals with chronic disease
      experience an exacerbation in oxidative stress following acute exercise when
      compared to healthy individuals. However, this increased oxidant stress may serve
      as a necessary "signal" for the upregulation in antioxidant defenses, thereby
      providing protection against subsequent exposure to prooxidant environments
      within susceptible individuals. Here we present studies related to both acute
      exercise-induced oxidative stress in those with disease, in addition to studies
      focused on adaptations resulting from increased RONS exposure associated with
      chronic exercise training in persons with disease.

PMID- 20046647
TI  - Contributions of mathematical modeling of beta cells to the understanding of beta
      cell oscillations and insulin secretion.
AB  - Mathematical modeling of pancreatic beta cells has contributed significantly to
      the understanding of the mechanisms involved in glucose-stimulated insulin
      secretion (GSIS). Early models of insulin secretion built in the 1970s were
      phenomenological with little biological foundation for the proposed mechanisms.
      In the 1980s, models focused on identifying the regulation of bursting electrical
      activity known to be important for insulin secretion. The main result was to
      reject proposed mechanisms as new data emerged, but important results of the role
      of cell-to-cell coupling were also established. New models have been proposed
      that provide possible explanations for the occurrence of various patterns of
      bursting and calcium oscillations. In addition, modeling has played an important
      role in comparing competing effects of calcium on both NADH and adenosine 3'-5'
      cyclic monophosphate levels. Models including modern cell biological results of
      the regulation of insulin containing granules and cell heterogeneity have
      appeared, providing updated versions of the early models proposed in the 1970s.
      These models, when coupled to electrophysiological- and calcium-based ones, have
      the prospect to aid in understanding the overall picture of GSIS. In addition,
      they might be useful for estimating in vivo beta-cell functioning. Beta-cell
      modeling will likely move closer to clinical applications, where it can be
      expected to play an important role, as it has and will, in understanding the
      complex oscillatory phenomena observed in beta cells and islets.

PMID- 20046648
TI  - System-level control to optimize glucagon counterregulation by switch-off of
      alpha-cell suppressing signals in beta-cell deficiency.
AB  - BACKGROUND: Glucagon counterregulation (GCR) is a key protection against
      hypoglycemia that is compromised in diabetes. In beta-cell-deficient rats, GCR
      pulsatility can be amplified if insulin (INS) or somatostatin (SS) are infused in
      the pancreatic artery and then switched off during hypoglycemia. The data
      indicate that these signals act by different mechanisms, and here we analyze the
      differences between the two switch offs (SOs) and predict the GCR-amplifying
      effect of their individual or combined application. METHODS: A minimal control
      network (MCN) of alpha/delta-cell interactions is approximated by differential
      equations to explain the GCR response to a SO and test in silico the hypotheses:
      (i) INS SO suppresses basal and pulsatile, while SS SO blocks only pulsatile
      glucagon release and (ii) simultaneous application of the two switch offs will
      augment the individual GCR response. RESULTS: The mechanism postulated in (i)
      explains the differences in the GCR responses between the SOs. The MCN predicts
      that simultaneous application of INS and SS decreases basal glucagon but
      increases post-SO amplitude, thus doubling the response of GCR achieved by each
      of the individual signals. CONCLUSION: The current analyses predict that INS and
      SS SOs improve defective GCR in beta-cell deficiency through different but
      complementary mechanisms and suggest SO strategies to maximally enhance GCR in
      type 1 diabetes by simultaneous manipulation of the network control. These
      results are clinically relevant, as they could have application to design of an
      artificial pancreas by providing ways to augment GCR that would not require
      glucagon infusion.

PMID- 20046649
TI  - Signal-response modeling of partial hormone feedback networks.
AB  - BACKGROUND: Endocrine feedback control networks are typically complex and contain
      multiple hormones, pools, and compartments. The hormones themselves commonly
      interact via multiple pathways and targets within the networks, and a complete
      description of such relationships may involve hundreds of parameters. In
      addition, it is often difficult, if not impossible, to collect experimental data
      pertaining to every component within the network. Therefore, the complete
      simultaneous analysis of such networks is challenging. Nevertheless, an
      understanding of these networks is critical for furthering our knowledge of
      hormonal regulation in both physiologic and pathophysiologic conditions. METHODS:
      We propose a novel approach for the analysis of dose-response relationships of
      subsets of hormonal feedback networks. The algorithm and signal-response
      quantification (SRQuant) software is based on convolution integrals, and tests
      whether several discretely measured input signals can be individually delayed,
      spread in time, transformed, combined, and discretely convolved with an
      elimination function to predict the time course of the concentration of an output
      hormone. Signal-response quantification is applied to examples from the endocrine
      literature to demonstrate its applicability to the analysis of the different
      endocrine networks. RESULTS: In one example, SRQuant determines the dose-response
      relationship by which one hormone regulates another, highlighting its advantages
      over other traditional methods. In a second example, for the first time (to the
      best of our knowledge), we show that the secretion of glucagon may be jointly
      controlled by the beta and the delta cells. CONCLUSION: We have developed a novel
      convolution integral-based approach, algorithm, and software (SRQuant) for the
      analysis of dose-response relationships within subsets of complex endocrine
      feedback control networks.

PMID- 20046650
TI  - Physical activity into the meal glucose-insulin model of type 1 diabetes: in
      silico studies.
AB  - INTRODUCTION: A simulation model of a glucose-insulin system accounting for
      physical activity is needed to reliably simulate normal life conditions, thus
      accelerating the development of an artificial pancreas. In fact, exercise causes
      a transient increase of insulin action and may lead to hypoglycemia. However,
      physical activity is difficult to model. In the past, it was described indirectly
      as a rise in insulin. Recently, a new parsimonious model of exercise effect on
      glucose homeostasis has been proposed that links the change in insulin action and
      glucose effectiveness to heart rate (HR). The aim of this study was to plug this
      exercise model into our recently proposed large-scale simulation model of glucose
      metabolism in type 1 diabetes to better describe normal life conditions. METHODS:
      The exercise model describes changes in glucose-insulin dynamics in two phases: a
      rapid on-and-off change in insulin-independent glucose clearance and a rapid
      on/slow-off change in insulin sensitivity. Three candidate models of glucose
      effectiveness and insulin sensitivity as a function of HR have been considered,
      both during exercise and recovery after exercise. By incorporating these three
      models into the type 1 diabetes model, we simulated different levels (from mild
      to moderate) and duration of exercise (15 and 30 minutes), both in steady-state
      (e.g., during euglycemic-hyperinsulinemic clamp) and in nonsteady state (e.g.,
      after a meal) conditions. RESULTS: One candidate exercise model was selected as
      the most reliable. CONCLUSIONS: A type 1 diabetes model also describing physical
      activity is proposed. The model represents a step forward to accurately describe
      glucose homeostasis in normal life conditions; however, further studies are
      needed to validate it against data.

PMID- 20046651
TI  - Treatment with sitagliptin or metformin does not increase body weight despite
      predicted reductions in urinary glucose excretion.
AB  - BACKGROUND: We used a mathematical model to estimate the contribution of urinary
      glucose excretion (UGE) to reported changes in body weight (BW) following oral
      antihyperglycemic agent (AHA) therapy. This modeling approach was used to gain
      novel insight into the mechanisms by which oral AHA affects BW. METHODS: Twenty
      four hour glucose profiles were used to predict UGE before and after treatment
      with oral AHA. Model-predicted changes in BW due to reduced UGE were compared
      with reported changes in BW to quantify non-UGE-dependent effects (fluid
      retention, food intake, and energy expenditure). RESULTS: In type 2 diabetes
      patients [hemoglobin A1c (HbA1c) >7.3%], the energy lost to UGE is predicted to
      decrease an average of 100 kcal/day for each 1% decrease in HbA1c. This effect,
      alone, is predicted to increase BW 1.4 kg after 6 months. Differences from this
      value reported for changes in BW with oral AHA therapy (+1.4 kg for pioglitazone
      and rosiglitazone; -0.4 kg for glyburide; -0.9 kg for sitagliptin and
      vildagliptin; -2.3 kg for metformin) are therefore predicted to be due to
      additional, non-UGE-dependent mechanisms. CONCLUSIONS: Weight gain following
      thiazolidinedione therapy is predicted to result from both reduced UGE and non
      UGE-dependent mechanisms. Reduced UGE alone is predicted to account for most of
      the weight gain reported following sulfonylurea therapy. Weight loss observed in
      response to metformin and weight maintenance observed in response to dipeptidyl
      peptidase-4 inhibitors may result from an increase in satiety, energy
      expenditure, or both.

PMID- 20046652
TI  - Self-monitoring of blood glucose in type 1 diabetes patients with insufficient
      metabolic control: focused self-monitoring of blood glucose intervention can
      lower glycated hemoglobin A1C.
AB  - OBJECTIVE: Little attention has been given and few studies have been published
      focusing on how to optimize self-monitoring of blood glucose (SMBG) use to
      monitor daily therapy for persons with type 1 diabetes mellitus. This study was
      designed to evaluate the effect on glycated hemoglobin (A1C) of a structured
      intervention focused on SMBG in type 1 diabetes patients with insufficient
      metabolic control (A1C >=8%) using a randomized clinical trial design. METHOD:
      One hundred fifty-nine outpatients with type 1 diabetes on multiple injection
      therapy with insulin and A1C >=8% were recruited and randomized to one group
      receiving a focused, structured 9-month SMBG intervention (n=59) and another
      group receiving regular care based on guidelines (n=64). RESULTS: Glycated
      hemoglobin values (mean % +/- standard deviation) at study start was similar:
      8.65 +/- 0.10 in the intervention group and 8.61 +/- 0.09 in the control group.
      The two groups were comparable (age, gender, body mass index, complication rate,
      and treatment modality) at study start and had mean diabetes duration and SMBG
      experience of 19 and 20 years, respectively. At study end, there was decrease in
      A1C in the intervention group (p<.05), and the A1C was 0.6% lower compared with
      the control group (p<.05). No increase in the number of minor or major
      hypoglycemia episodes was observed in the intervention group during the study
      period. CONCLUSIONS: A simple, structured, focused SMBG intervention improved
      metabolic control in patients with longstanding diabetes type 1 and A1C >=8%. The
      intervention was based on general recommendations, realistic in format, and can
      be applied in a regular outpatient setting.

PMID- 20046653
TI  - Coordinated basal-bolus infusion for tighter postprandial glucose control in
      insulin pump therapy.
AB  - BACKGROUND: Basal and bolus insulin determination in intensive insulin therapy
      for type 1 diabetes mellitus (T1DM) are currently considered independently of
      each other. A new strategy that coordinates basal and bolus insulin infusion to
      cope with postprandial glycemia in pump therapy is proposed. Superior performance
      of this new strategy is demonstrated through a formal analysis of attainable
      performances in an in silico study. METHODS: The set inversion via interval
      analysis algorithm has been applied to obtain the feasible set of basal and bolus
      doses that, for a given meal, mathematically guarantee a postprandial response
      fulfilling the International Diabetes Federation (IDF) guidelines (i.e., no
      hypoglycemia and 2 h postprandial glucose below 140 mg/dl). Hypoglycemia has been
      defined as a glucose value below 70 mg/dl. A 5 h time horizon has been considered
      for a 70 kg in silico T1DM subject consuming meals in the range of 30 to 80 g of
      carbohydrates. RESULTS: The computed feasible sets demonstrate that current
      separated basal/bolus strategy dramatically limits the attainable performance.
      For a nominal basal of 0.8 IU/h leading to a basal glucose of approximately 100
      mg/dl, IDF guidelines cannot be fulfilled for meals greater than 50 g of
      carbohydrates, independent of the bolus insulin computed. However, coordinating
      the basal and bolus insulin delivery can achieve this. A decrement of basal
      insulin during the postprandial period is required together with an increase in
      bolus insulin, in appropriate percentages, which is meal dependent. After 3 h,
      basal insulin can be restored to its nominal value. CONCLUSIONS: The new strategy
      meets IDF guidelines in a typical day, contrary to the standard basal/bolus
      strategy, yielding a mean 2 h postprandial glucose reduction of 36.4 mg/dl
      without late hypoglycemia. The application of interval analysis for the
      computation of feasible sets is demonstrated to be a powerful tool for the
      analysis of attainable performance in glucose control.

PMID- 20046654
TI  - Clinical evaluation of a transcutaneous interrogated fluorescence lifetime-based
      microsensor for continuous glucose reading.
AB  - BACKGROUND: Continuous glucose monitoring is presently used worldwide. Accuracy,
      precision, durability, invasiveness, and lack of drift of sensors and lag time
      are key parameters essential to these systems. This article describes a new
      online minimally invasive biodegradable microsensor for optical, transcutaneous
      interrogation, which has at least 14 days of functionality. METHOD: Studies were
      performed in vitro and in vivo on pigs, as well as on type 1 diabetic humans.
      Functionality has been ensured in laboratory settings, and precision and
      durability have been tested in vivo. During in vivo studies, venous blood samples
      were used as reference. Results were based on one single point calibration per
      experiment. RESULTS: Excellent stability was found in 14-day in vitro trials as
      well as in vivo in up to 70-hour trials. The overall median relative absolute
      difference of type 1 diabetic patients was 11.4%. Error grid analysis showed
      97.7% of all values in the A+B zone. Comparable results were found in animal
      studies. No sensor drift was observed in any trial. CONCLUSION: Results point
      toward the possibility of developing a stable and precise minimally invasive
      glucose reader for at least 2 weeks of continuous use.

PMID- 20046655
TI  - An automated discontinuous venous blood sampling system for ex vivo glucose
      determination in humans.
AB  - BACKGROUND: Intensive insulin therapy reduces mortality and morbidity in
      critically ill patients but places great demands on medical staff who must take
      frequent blood samples for the determination of glucose levels. A cost-effective
      solution to this resourcing problem could be provided by an effective and
      reliable automated blood sampling (ABS) system suitable for ex vivo glucose
      determination. METHOD: The primary study aim was to compare the performance of a
      prototype ABS system with a manual reference system over a 30 h sampling period
      under controlled conditions in humans. Two venous cannulae were inserted to
      connect the ABS system and the reference system. Blood samples were taken with
      both systems at 15, 30, and 60 min intervals and analyzed using a Beckman glucose
      analyzer. During the study, blood glucose levels were altered through four meal
      ingestions. RESULTS: The median Pearson coefficient of correlation between
      manually and automatically withdrawn blood samples was 0.976 (0.953-0.996). The
      system error was -3.327 +/- 5.546% (-6.03-0.49). Through Clark error grid
      analysis, 420 data pairs were analyzed, showing that 98.6% of the data were in
      zone A and 1.4% were in zone B. Insulin titration error grid analysis revealed an
      acceptable treatment in 100% of cases. A 17.5-fold reduction in the occurrence of
      blood-withdrawal failures through occluded catheters was moreover achieved by the
      added implementation in the ABS system of a "keep vein open" saline infusion.
      CONCLUSIONS: Our study showed that the ABS system described provides a user
      friendly, reliable automated means for reproducible and accurate blood sampling
      from a peripheral vein for blood glucose determination and thus represents a
      promising alternative to frequent manual blood sampling.

PMID- 20046657
TI  - Smart home-based health platform for behavioral monitoring and alteration of
      diabetes patients.
AB  - BACKGROUND: Researchers and medical practitioners have long sought the ability to
      continuously and automatically monitor patients beyond the confines of a doctor's
      office. We describe a smart home monitoring and analysis platform that
      facilitates the automatic gathering of rich databases of behavioral information
      in a manner that is transparent to the patient. Collected information will be
      automatically or manually analyzed and reported to the caregivers and may be
      interpreted for behavioral modification in the patient. METHOD: Our health
      platform consists of five technology layers. The architecture is designed to be
      flexible, extensible, and transparent, to support plug-and-play operation of new
      devices and components, and to provide remote monitoring and programming
      opportunities. RESULTS: The smart home-based health platform technologies have
      been tested in two physical smart environments. Data that are collected in these
      implemented physical layers are processed and analyzed by our activity
      recognition and chewing classification algorithms. All of these components have
      yielded accurate analyses for subjects in the smart environment test beds.
      CONCLUSIONS: This work represents an important first step in the field of smart
      environment-based health monitoring and assistance. The architecture can be used
      to monitor the activity, diet, and exercise compliance of diabetes patients and
      evaluate the effects of alternative medicine and behavior regimens. We believe
      these technologies are essential for providing accessible, low-cost health
      assistance in an individual's own home and for providing the best possible
      quality of life for individuals with diabetes.

PMID- 20046656
TI  - Changes in diabetes distress related to participation in an internet-based
      diabetes care management program and glycemic control.
AB  - BACKGROUND: This article investigated how changes in diabetes distress relate to
      receiving care management through an Internet-based care management (IBCM)
      program for diabetes and level of participation in this program. Further, it
      examined the relationship between diabetes distress and changes in glycemic
      control. METHODS: We enrolled patients of the Veterans Affairs Boston Healthcare
      System with diabetes who had hemoglobin A1c (HbA1c) levels of >=9.0%. Subjects
      were randomized to usual care (n=52) or IBCM (n=52) for 1 year. We measured
      diabetes distress at baseline and quarterly thereafter using the Problem Areas in
      Diabetes (PAID) questionnaire. Glycemic control was determined by baseline and
      quarterly HbA1c. For subjects randomized to IBCM, we measured participation by
      observing frequency and consistency of their usage of the IBCM patient portal
      over 12 months. Linear mixed models were used to analyze THE data. RESULTS: PAID
      scores declined over time for both treatment groups. Among subjects randomized to
      IBCM, the decline in PAID scores over time was significant for sustained users of
      the IBCM patient portal but not for nonusers. Moreover, subjects whose usage of
      the patient portal was sustained throughout the study had lower PAID scores at
      baseline. With respect to changes in glycemic control, HbA1c reduced individual
      differences in PAID scores by 44%; a lower baseline HbA1c was associated with
      lower baseline PAID scores, and over time, the decrease in HbA1c was associated
      with further decreases in the PAID score. CONCLUSIONS: Participation in IBCM
      varies by initial diabetes distress, with people with less distress participating
      more. For people who participate, IBCM further mitigates diabetes distress. There
      is also a relationship between achievements in glycemic control and subsequent
      lowering of diabetes distress. Future research should identify how to maximize
      fit between patient needs and the provisions of IBCM, with the aim of increasing
      patient engagement in the active management of their health using this care
      modality. A key to maximizing fit might be first addressing metabolic control
      aggressively and then using IBCM for sustainment of health.

PMID- 20046658
TI  - Comparison of the dose accuracy of prefilled insulin pens.
AB  - BACKGROUND: Prefilled insulin pens have become a convenient and accurate way for
      diabetes patients to inject insulin. Their ease of use has helped to reduce the
      resistance of patients with type 1 diabetes and type 2 diabetes in the United
      States and Europe toward initiation of insulin therapy. This study compared the
      dosing accuracy of two prefilled insulin pens (the SoloStar((R)) from Sanofi
      Aventis, Berlin, Germany, and the Next Generation [NG] FlexPen((R)) from Novo
      Nordisk, Mainz, Germany). METHODS: The dosing accuracy was tested for both pens
      with x 24 10 international units of insulin (IU) and 9 x 30 IU injection volumes
      to investigate whether the pens comply within the acceptable International
      Organization for Standardization (ISO) limits of 10% (+/-1 IU) for 10 IU and 5%
      (+/-1.5 IU) for 30 IU. The doses were applied each with a new needle strictly
      according to the instructions for use of the pen manufacturers. A sensitive
      pharmaceutical balance was used for the assessment of the applied volumes, and
      the results were corrected for the specific density of the insulin formulations.
      We used 18 insulin pens (from two different production lots each) for the two
      volumes, respectively, resulting in a total of 432 doses per pen with 10 IU and
      162 doses per pen with 30 IU. RESULTS: Both pens showed a very good performance,
      which was better for the 10 IU dose than in comparative previous studies. The NG
      FlexPen (mean absolute percent deviation 10 IU/30 IU: 1.63 +/- 0.84%/1.23 +/-
      0.76%) was even more accurate than the SoloStar (2.11 +/- 0.92%/1.54 +/- 0.84%, p
      < .001/p < .05 versus the NG FlexPen). Only 0.2% of the doses were outside the
      ISO limit at 10 IU, with the NG FlexPen (0.6% at 30 IU). The corresponding
      figures for the SoloStar were 0.4% and 1.8%, respectively. CONCLUSIONS: A direct
      head-to-head comparison of the two prefilled insulin pens with a standardized
      protocol resulted in a more stable dosing accuracy of both pens as compared to
      previous investigations. In this investigation, the NG FlexPen was more accurate
      than the SoloStar at both tested doses.

PMID- 20046659
TI  - Analysis of studies that compare the dose accuracy of prefilled insulin pens.
AB  - Multiple industry-sponsored studies have been published about the accuracy of
      insulin delivery using prefilled insulin pens. Although the study by Weise and
      colleagues in this issue of Journal of Diabetes Science and Technology found that
      the Novo Nordisk device was slightly more accurate than the Sanofi-Aventis
      device, one can anticipate a Sanofi-Aventis-funded study that may find the
      opposite, because no internationally acceptable, publicly funded, unbiased
      scientific organization exists to perform head-to-head comparisons of drugs and
      devices in an evidence-based manner. Currently, clinicians are left on their own
      to determine whether a study on this topic was conducted in an accurate, unbiased
      manner. A fundamental redesign of clinical research could reinvigorate and
      revolutionize the process by which innovations travel from the bench to the
      bedside. As we anticipate changes in healthcare in the future, it is imperative
      that the approval and postmarketing surveillance process is revised to support
      the practice of true evidence-based medicine.

PMID- 20046660
TI  - A liquid chromatography/tandem mass spectrometry method for determination of 25
      hydroxy vitamin D2 and 25-hydroxy vitamin D3 in dried blood spots: a potential
      adjunct to diabetes and cardiometabolic risk screening.
AB  - BACKGROUND: Now emerging as an important risk factor for type 1 diabetes, vitamin
      D deficiency is also associated with obesity, metabolic syndrome, and type 2
      diabetes and has been identified as a potential cardiometabolic risk factor. A
      simple, accurate screening test for 25-hydroxy vitamin D [25(OH)D] deficiency is
      needed. We developed a liquid chromatography/tandem mass spectrometry assay for
      25-hydroxy vitamin D(2) [25(OH)D(2)] and 25-hydroxy vitamin D(3) [25(OH)D(3)] in
      dried blood spots. METHOD: Blood spots were collected by finger stick
      simultaneously with serum samples obtained by venipuncture from healthy
      volunteers. Disks punched from the dried blood spots were sonicated with an
      internal standard solution of deuterated 25(OH)D(3) (26,26,26,27,27,27-d(6)).
      Methanol was added to precipitate proteins prior to extraction with hexane. The
      extracted samples were dried and reconstituted in 50:50 methanol:H(2)O before
      injection into a Varian 320-MS TQ mass spectrometer. RESULTS: BLOOD SPOT ASSAY
      PRECISION WAS GOOD OVER THE REPORTABLE RANGE: interassay coefficients of
      variation were 13, 13, and 11% at concentrations of 14, 26, and 81 ng/ml,
      respectively, for 25-hydroxy vitamin D(3) and 12% at 23 ng/ml for 25(OH)D(2). The
      25(OH)D(3) assay was linear from 3.5 to 75 ng/ml (R > 0.99). Blood spot and serum
      values showed excellent correlation for 25(OH)D(2) (R=0.90, n=54) and 25(OH)D(3)
      (R=0.91, n=83). CONCLUSIONS: This blood spot assay for 25(OH)D(2) and 25(OH)D(3)
      provides a convenient and cost-effective alternative to serum assays and can be
      automated. This may be valuable in large-scale screening for risk of type 1
      diabetes, for cardiometabolic risk screening, and for monitoring vitamin D
      supplementation.

PMID- 20046662
TI  - Pharmacists' role in improving diabetes medication management.
AB  - Today there are significant gaps between reaching the goal of "optimal medication
      therapy" and the current state of medication use in the United States.
      Pharmacists are highly accessible and well-trained--yet often underutilized--key
      health care professionals who can move us closer toward achieving better
      medication therapy outcomes for patients. Diabetes medication management programs
      led by pharmacists are described. This is consistent with the "medical home"
      concept of care that promotes primary care providers working collaboratively to
      coordinate patient-centered care. Pharmacists utilize their clinical expertise in
      monitoring and managing diabetes medication plans to positively impact health
      outcomes and empower patients to actively manage their health. In addition,
      pharmacists can serve as a resource to other health care providers and payers to
      assure safe, appropriate, cost-effective diabetes medication use.

PMID- 20046661
TI  - Medical implications of obesity in horses--lessons for human obesity.
AB  - There is growing recognition that obesity is common and represents a significant
      detriment to the health of companion animals in a manner similar to that by which
      it is affecting the human population. As is the case for other species, obesity
      appears to promote insulin resistance in horses and it is through this
      pathophysiological process that many of the adverse medical consequences of
      obesity are being characterized. Equine medical conditions that have been
      described in the context of obesity and insulin resistance differ from those in
      humans. Chronic human conditions that have been attributed to obesity and insulin
      resistance, such as atherosclerosis and diabetes mellitus, are rarely described
      in obese horses. Significant current interest is centered on the recognition that
      insulin resistance plays a role in the pathogenesis of laminitis, a potentially
      severe and debilitating cause of lameness in the equine species. Other equine
      medical conditions that are more likely in obese, insulin-resistant individuals
      include hyperlipemia (hepatic lipidosis) and developmental orthopedic disease
      (osteochondrosis). Pituitary pars intermedia dysfunction (equine Cushing's
      syndrome) represents another common endocrinopathic condition of older horses
      associated with insulin resistance. This review presents an introductory overview
      of the present understanding of obesity and insulin resistance and how these
      conditions may be associated with disease conditions in horses.

PMID- 20046663
TI  - The potential use of radio frequency identification devices for active monitoring
      of blood glucose levels.
AB  - Imagine a diabetes patient receiving a text message on his mobile phone warning
      him that his blood glucose level is too low or a patient's mobile phone calling
      an emergency number when the patient goes into diabetic shock.Both scenarios
      depend on automatic, continuous monitoring of blood glucose levels and
      transmission of that information to a phone. The development of advanced
      biological sensors and integration with passive radio frequency identification
      technologies are the key to this. These hold the promise of being able to free
      patients from finger stick sampling or externally worn devices while providing
      continuous blood glucose monitoring that allows patients to manage their health
      more actively. To achieve this promise, however, a number of technical issues
      need to be addressed.

PMID- 20046664
TI  - Recent advances in internet-delivered, evidence-based weight control programs for
      adults.
AB  - With the explosion of Internet accessibility, online delivery offers potential
      for significantly greater reach of evidence-based obesity treatment programs for
      adults. Online behavioral weight control has been shown to produce significant
      weight loss, with more recent programs demonstrating larger losses and general
      consumer satisfaction. A growing literature indicates several program parameters
      that may offer greatest engagement in online obesity interventions and better
      weight loss outcomes, including interactive, dynamic Web site features and
      synchronous counselor contact, although this research is in the early stages, and
      a clear picture of the essential components for the most effective online obesity
      program remains to be determined. Further research is required to enhance weight
      loss outcomes, determine cost-effectiveness of Internet-delivered programs, and
      identify the individuals most likely to benefit from treatment in this format.

PMID- 20046665
TI  - Incorporating a generic model of subcutaneous insulin absorption into the AIDA v4
      diabetes simulator. 3. Early plasma insulin determinations.
AB  - INTRODUCTION: AIDA is an interactive educational diabetes simulator that has been
      available without charge via the Internet for over 12 years. Recent articles have
      described the incorporation of a novel generic model of insulin absorption into
      AIDA as a way of enhancing its capabilities. The basic model components to be
      integrated have been overviewed, with the aim being to provide simulations of
      regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU
      (the current upper limit within the latest release of AIDA [v4.3a]). Some
      preliminary calculated insulin absorption results have also recently been
      described. METHODS: This article presents the first simulated plasma insulin
      profiles from the integration of the generic subcutaneous insulin absorption
      model, and the currently implemented model in AIDA for insulin disposition.
      Insulin absorption has been described by the physiologically based model of Tarin
      and colleagues. A single compartment modeling approach has been used to specify
      how absorbed insulin is distributed in, and eliminated from, the human body. To
      enable a numerical solution of the absorption model, a spherical subcutaneous
      depot for the injected insulin dose has been assumed and spatially discretized
      into shell compartments with homogeneous concentrations, having as its center the
      injection site. The number of these compartments will depend on the dose and type
      of insulin. Insulin inflow arises as the sum of contributions to the different
      shells. For this report the first bench testing of plasma insulin determinations
      has been done. RESULTS: Simulated plasma insulin profiles are provided for
      currently available insulin preparations, including a rapidly acting insulin
      analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular)
      insulin preparation (e.g., Actrapid), intermediate-acting insulins (both
      Semilente and neutral protamine Hagedorn types), and a very long-acting insulin
      analogue (e.g., glargine/Lantus), as well as for insulin doses up to 50 IU.
      DISCUSSION: The methodology to be adopted for implementing the generic absorption
      model within AIDA has been overviewed, and the first plasma insulin profiles
      based on this approach have been demonstrated. Ideas for future work and
      development are discussed. It is expected that an updated release of AIDA (v4.5),
      based on this collaborative approach, will become available for free--in due
      course--via the www.2aida.org Web site. Readers who wish to be informed when the
      new software is launched can join the very low volume AIDA announcement list by
      sending a blank email note to subscribe@2aida.org.

PMID- 20046666
TI  - A review of health literacy and diabetes: opportunities for technology.
AB  - BACKGROUND: The objective of this study was to assess the published literature on
      health literacy and diabetes, as well as identify opportunities for technology to
      strengthen information skills and modify behavior to improve diabetes health
      outcomes. METHODS: Medline (1990-2008), the Cumulative Index to Nursing and
      Allied Health Literature (1990-2008), and the Education Resources Information
      Center (1990-2008) were searched, and reference lists from included articles were
      reviewed to identify additional studies. Articles were included that presented
      measures of literacy or numeracy specific to diabetes, examined associations
      between health literacy and diabetes outcomes, or tested a health literacy
      intervention among persons with diabetes. RESULTS: Twenty-four articles were
      included in this review. Five articles reported on measures of literacy or
      numeracy specific to diabetes. Thirteen of the fifteen cross-sectional studies
      (87%) associated limited health literacy with poorer diabetes outcomes. Two of
      the four (50%) health literacy intervention studies lead to improved health
      outcomes. CONCLUSIONS: The cross-sectional studies provide evidence of an
      association between health literacy and diabetes outcomes; however, there is a
      need to design and test strategies to improve diabetes health outcomes that
      consider health literacy. Information and communication technology opportunities
      could help to mediate the effect that limited health literacy has on diabetes
      related health outcomes.

PMID- 20046667
TI  - Trust: need for an improved communication between the public world and the
      pharmaceutical companies.
AB  - In the industrialized world, the negative image that many people (including
      politicians) have of pharmaceutical companies not only makes the life for those
      working in this field more difficult, in a sense it is a road block. Without an
      improvement in communication between the public world and the pharmaceutical
      industry, one can foresee this industry steadily becoming a more difficult
      environment to work in. There is a clear need for knowing more about all the work
      done inside these companies before a new drug is approved (it is not all about
      marketing...). That society has no understanding of the ever-increasing costs of
      new drugs is also related to this lack of understanding of how tricky and
      cumbersome the process is to take a new idea for treating a certain disease to
      production of a marketed drug. With a relatively small investment of money, but
      with an investment of much good will, brain power, and trust, it should be
      possible to bring all relevant parties together and make a change.

PMID- 20046668
TI  - The impact of insulin adsorption onto the infusion sets in the adult intensive
      care unit.

PMID- 20046669
TI  - Cryopreservation and the age of the allotransplant.
AB  - For centuries, reconstructive surgeons have restored form and function with
      autografts. These techniques are highly effective, but they are associated
      invariably with donor site morbidity. To avoid this, surgeons have long dreamed
      of using cadaveric sources for reconstructive material. However, allografts have
      two major limitations: rejection and limited donor tissue. In order to limit
      rejection, the allograft must be rendered more tolerable to the host or the host
      must be rendered more tolerant of the allograft. Both strategies have been used
      with considerable success in recent years. As understanding of the human immune
      response increases, clinical immunosuppressive regimens will undoubtedly become
      less morbid, and the indications for allotransplantation will broaden. This will
      place an even greater burden on the already small donor pool. One way to relieve
      this burden would be through the development of strategies for the long-term
      preservation of donated tissues and organs. Cryopreservation has been used
      clinically for decades, and recent advances in the field have allowed the
      preservation of an ever widening array of tissues and organs. As cold storage has
      been shown to reduce the antigenicity of parts, cryopreservation may actually
      serve to improve the survival rate of transplanted parts, as well as increase
      their availability. As the era of autotransplantation gives way to the age of
      allotransplantation, cryopreservation will play an increasingly important role.

PMID- 20046670
TI  - Cryopreservation: An emerging paradigm change.

PMID- 20046671
TI  - Cryopreservation of vascular tissues.
AB  - Cryopreservation of human blood vessels may become an important tool in bypass
      surgery and peripheral vascular reconstruction. Ideally cryopreservation of a
      blood vessel should preserve functional characteristics comparable to those of
      fresh controls. The key advantage of cryopreservation is the fact that storage at
      deep subzero temperatures allows storage of structurally intact living vascular
      tissues for virtually infinite time. Originally developed for long-time storage
      of isolated cells, the techniques of cryopreservation of tissues are challenged
      by the fact that these are complex multicellular systems containing diverse types
      of cells with differing requirements for optimal preservation. Therefore, the
      post-thaw functional activity of vascular tissues is determined by the type of
      blood vessel and, in addition, by the cell packing effect. Moreover, evidence
      from pharmacological studies suggests that cryopreservation induces tissue
      specific changes in transmembrane signaling and the mechanisms coupling
      intracellular calcium release, sensitivity and calcium entry into the smooth
      muscle cells.

PMID- 20046672
TI  - Preservation methods for kidney and liver.
AB  - With the successful testing of the immunosuppressive effects of cyclosporine in
      transplant patients in 1978, the field of organ transplants began an exponential
      growth. With that, the field of organ preservation became increasingly important
      as the need to increase preservation time and improve graft function became
      paramount. However, for every patient that receives a transplanted organ, there
      are four more on the waiting list. In addition, a patient dies from the lack of a
      transplant almost every 1(1/2) hour. To alleviate this donor crisis, there is a
      need to expand the donor pool to marginal donor organs. The main reason these
      organs are underutilized is because the current method of static preservation,
      simple cold storage, is ineffective. This article will provide a general review
      of the methods of preservation including simple cold storage, hypothermic machine
      perfusion, normothermic machine perfusion, and oxygen persufflation. In addition,
      the article will provide a review of how these dynamic preservation methods have
      improved the recovery and preservation of marginal donor organs including
      Donation after Cardiac Death and Fatty livers.

PMID- 20046673
TI  - Cryopreservation of the tracheal grafts: Review and perspective.
AB  - Transplantation of the trachea may become the preferred method for the
      reconstruction of extensive tracheal defects, however, several unresolved
      problems must be addressed, such as immunosuppression, preservation and donor
      shortage. In this manuscript, the cryopreservation of tracheal grafts is
      reviewed, which potentially is associated with a lessened immunological response.
      Cryopreservation may be used clinically for long-term preservation and may solve
      the donor shortage. It is very important to confirm the immunomodulatory effect
      of cryopreservation on tracheal allografts in order to expand the potential
      clinical application of tracheal transplantation in the future. The cartilage as
      well as the epithelium and lamina propria serve as targets for rejection.
      However, the effect of cryopreservation on chondrocytes could be associated with
      reduced allogenicity of the trachea. The long-term cryopreservation of cartilage
      must be investigated in basic research models of chondrocyte viability. Growth of
      cryopreserved tracheal allografts is less well understood. Further studies are
      needed to elucidate the mechanism of synergistic effects of both cryopreservation
      and adequate immunosuppression for tracheal xenografts.

PMID- 20046674
TI  - The cryopreservation of composite tissues: Principles and recent advancement on
      cryopreservation of different type of tissues.
AB  - Cryopreservation of human cells and tissue has generated great interest in the
      scientific community since 1949, when the cryoprotective activity of glycerol was
      discovered. Nowadays, it is possible to reach the optimal conditions for the
      cryopreservation of a homogeneous cell population or a one cell-layer tissue with
      the preservation of a high pourcentage of the initial cells. Success is attained
      when there is a high recovery rate of cell structures and tissue components after
      thawing. It is more delicate to obtain cryopreservation of composite tissues and
      much more a whole organ. The present work deals with fundamental principles of
      the cryobiology of biological structures, with special attention to the transfer
      of liquids between intra and extracellular compartments and the initiation of the
      formation and aggregation of ice during freezing. The consequences of various
      physical and chemical reactions on biological tissue are described for different
      cryoprotective agents. Finally, we report a review of results on cyropreservation
      of various tissues, on the one hand, and various organs, on the other. We also
      report immunomodulation of antigenic responses to cryopreserved cells and organs.

PMID- 20046675
TI  - Xenotransplantation of cryopreserved composite organs on the rabbit.
AB  - Nowadays, It is easy to define optimal conditions (cryoprotective agent, speed
      and steps of freezing, speed of warming) for the cryopreservation of a
      homogeneous cell population or a one cell-layer tissue. Meanwhile, It is still
      hard to obtain cryopreservation of composite organs. Each tissue has its own
      requirements and its own reactivity to the cryopreservation process. The
      challenge consists of, on the one hand, to select the ideal combination of
      cryoprotective agents that can fit the needs of the different tissues, and the
      definition of adequate technical parameters, on the other hand. All the
      experimental trials have studied the survival rate of non-vascularized
      cryopreserved tissues. The aim of our experimental work is to demonstrate the
      feasibility of cryopreserving a composite organ with its nutrient vessels "artery
      and veins" in order after thawing to revitalize it by reestablishing the blood
      irrigation by microsurgical vascular anastomosis. We report our experimental
      results on the cryopreservation of composite organs-amputated digits
      xenotransplanted in the rabbit. Digital segments were cryopreserved, then
      revitalized after warming using vascular microsurgical techniques. Preliminary
      results are encouraging and may pave the way in the future to the microvascular
      allotransplantation of cryopreserved composite organs.

PMID- 20046676
TI  - Preservation of stem cells.
AB  - Adult stem cells (hematopoietic and mesenchymal) have demonstrated tremendous
      human therapeutic potential. Currently, human embryonic stem cells are used
      principally for understanding development and disease progression but also hold
      tremendous therapeutic potential. The ability to preserve stem cells is critical
      for their use in clinical and research applications. Preservation of cells
      permits the transportation of cells between sites, as well as completion of
      safety and quality control testing. Preservation also permits the development of
      a 'manufacturing paradigm' for cell therapies, thereby maximizing the number of
      products that can be produced at a given facility. in this article, we will
      review modes of preservation and the current status of preservation of
      hematopoietic, mesenchymal and human embryonic stem cells. Current and emerging
      issues in the area of stem cell preservation will also be described.

PMID- 20046677
TI  - Cryopreservation of adipose tissue.
AB  - The main obstacle to achieving favorable outcome of soft-tissue augmentation
      after autologous fat transplantation is unpredictable long-term results due to
      the high rate of absorption in the grafted site. At the present time, adipose
      aspirates can only be used for immediate autologous fat grafting during the same
      procedure in which liposuction is performed; therefore adipose aspirates obtained
      from the procedure are usually discarded. it has been a strong desire of both
      surgeons and patients to be able to preserve the adipose aspirates, if an optimal
      technique were available, for potential future applications. For the last several
      years, cryopreservation of adipose tissue has been studied extensively in the
      author's laboratory. Several findings from this exciting translational research
      will lead to develop a reliable method for long-term preservation of adipose
      tissue in the future. in addition, successful long-term preservation of adipose
      tissue may open a new era in adipose tissue related tissue regeneration.

PMID- 20046678
TI  - Clinical grade adult stem cell banking.
AB  - There has been a great deal of scientific interest recently generated by the
      potential therapeutic applications of adult stem cells in human care but there
      are several challenges regarding quality and safety in clinical applications and
      a number of these challenges relate to the processing and banking of these cells
      ex-vivo. As the number of clinical trials and the variety of adult cells used in
      regenerative therapy increases, safety remains a primary concern. This has
      inspired many nations to formulate guidelines and standards for the quality of
      stem cell collection, processing, testing, banking, packaging and distribution.
      Clinically applicable cryopreservation and banking of adult stem cells offers
      unique opportunities to advance the potential uses and widespread implementation
      of these cells in clinical applications. Most current cryopreservation protocols
      include animal serum proteins and potentially toxic cryoprotectant additives
      (CPAs) that prevent direct use of these cells in human therapeutic applications.
      Long term cryopreservation of adult stem cells under good manufacturing
      conditions using animal product free solutions is critical to the widespread
      clinical implementation of ex-vivo adult stem cell therapies. Furthermore, to
      avoid any potential cryoprotectant related complications, reduced CPA
      concentrations and efficient post-thaw washing to remove CPA are also desirable.
      The present review focuses on the current strategies and important aspects of
      adult stem cell banking for clinical applications. These include current good
      manufacturing practices (cGMPs), animal protein free freezing solutions,
      cryoprotectants, freezing & thawing protocols, viability assays, packaging and
      distribution. The importance and benefits of banking clinical grade adult stem
      cells are also discussed.

PMID- 20046679
TI  - Review of vitreous islet cryopreservation: Some practical issues and their
      resolution.
AB  - Transplantation of pancreatic islets for the treatment of diabetes mellitus is
      widely anticipated to eventually provide a cure once a means for preventing
      rejection is found without reliance upon global immunosuppression. Long-term
      storage of islets is crucial for the organization of transplantation, islet
      banking, tissue matching, organ sharing, immuno-manipulation and multiple donor
      transplantation. Existing methods of cryopreservation involving freezing are
      known to be suboptimal providing only about 50% survival. The development of
      techniques for ice-free cryopreservation of mammalian tissues using both natural
      and synthetic ice blocking molecules, and the process of vitrification (formation
      of a glass as opposed to crystalline ice) has been a focus of research during
      recent years. These approaches have established in other tissues that
      vitrification can markedly improve survival by circumventing ice-induced injury.
      Here we review some of the underlying issues that impact the vitrification
      approach to islet cryopreservation and describe some initial studies to apply
      these new technologies to the long-term storage of pancreatic islets. These
      studies were designed to optimize both the pre-vitrification hypothermic exposure
      conditions using newly developed media and to compare new techniques for ice-free
      cryopreservation with conventional freezing protocols. Some practical constraints
      and feasible resolutions are discussed. Eventually the optimized techniques will
      be applied to clinical allografts and xenografts or genetically-modified islets
      designed to overcome immune responses in the diabetic host.

PMID- 20046680
TI  - Physical and biological aspects of renal vitrification.
AB  - Cryopreservation would potentially very much facilitate the inventory control and
      distribution of laboratory-produced organs and tissues. Although simple freezing
      methods are effective for many simple tissues, bioartificial organs and complex
      tissue constructs may be unacceptably altered by ice formation and dissolution.
      Vitrification, in which the liquids in a living system are converted into the
      glassy state at low temperatures, provides a potential alternative to freezing
      that can in principle avoid ice formation altogether. The present report provides
      a brief overview of the problem of renal vitrification. We report here the
      detailed case history of a rabbit kidney that survived vitrification and
      subsequent transplantation, a case that demonstrates both the fundamental
      feasibility of complex system vitrification and the obstacles that must still be
      overcome, of which the chief one in the case of the kidney is adequate
      distribution of cryoprotectant to the renal medulla. Medullary equilibration can
      be monitored by monitoring urine concentrations of cryoprotectant, and urine flow
      rate correlates with vitrification solution viscosity and the speed of
      equilibration. By taking these factors into account and by using higher perfusion
      pressures as per the case of the kidney that survived vitrification, it is
      becoming possible to design protocols for equilibrating kidneys that protect
      against both devitrification and excessive cryoprotectant toxicity.

PMID- 20046681
TI  - Fractional laser photothermolysis for treatment of facial wrinkles in Asians.
AB  - PURPOSE: To evaluate the safety and efficacy of fractional photothermolysis (FP)
      in the treatment of facial wrinkles in Asians. METHODS: A total of 27 Korean
      patients (Fitzpatrick type III or IV) received 2-3 FP treatment sessions (Sellas;
      Dinona Inc., Seoul, Korea) spaced two weeks apart. Treatments were performed at
      settings of 7 to 9 mJ/microthermal treatment zone (MTZ) and a density of 1000
      MTZ/cm(2). Standardized digital photographs were obtained before each treatment
      and three months after the final treatment. The evaluations of clinical
      photographs were performed by three physicians blinded to the study subjects
      using a five-point grading scale. In addition, the patients' perceived degree of
      improvement was assessed three months after the final treatment using a five
      point grading scale. Side effects were monitored at each follow-up visit.
      RESULTS: The physicians' assessed degrees of improvement were excellent in three
      patients (12%), significant in ten (40%), and moderate in seven (28%). The
      patients' self-assessed degrees of improvement were excellent in five patients
      (20%), significant in 11 (44%), and moderate in six (24%). Adverse events were
      limited to transient pain, erythema and edema, except in one case of transient
      postinflammatory hyperpigmentation. CONCLUSIONS: FP is an effective treatment
      modality for reducing facial wrinkles with minimal side effects in Asian
      patients.

PMID- 20046682
TI  - Perioperative modulating factors on astigmatism in sutured cataract surgery.
AB  - PURPOSE: To evaluate the factors that affect postoperative astigmatism and post
      suture removal astigmatism, and to evaluate the risk factors associated with
      astigmatism axis shift. METHODS: We performed a retrospective chart review of 130
      eyes that had undergone uneventful phacoemulsification cataract surgery.
      Preoperative astigmatism was divided into four groups (Groups I, II, III, and IV)
      according to the differences between the axis of preoperative astigmatism
      (flattest axis) and the incision axis (105 degrees). We analyzed the magnitude
      and axis of the induced astigmatism after the operation and after suture removal
      in each group. We also analyzed the factors which affected the postoperative
      astigmatism and post-suture removal astigmatism in each sub-group of Groups I,
      II, III, and IV, excluding postoperative or post-suture removal axis shift
      (specifically, Group I(WAS), II(WAS), III(WAS), and IV(WAS)). We identified the
      variables associated with the prevalence of postoperative astigmatism axis shift
      and those associated with the prevalence of post-suture removal axis shift.
      RESULTS: An increase in the magnitude of postoperative astigmatism was associated
      with an increase in the preoperative magnitude of astigmatism in Groups I(WAS),
      II(WAS), and III(WAS) (p<0.05), and with an increase in the corneal tunnel length
      in Group I(WAS). A decrease in the magnitude of postoperative astigmatism was
      associated with an increase in the corneal tunnel length in Groups III(WAS) and
      IV(WAS) (p<0.05). An increase in the magnitude of post-suture removal astigmatism
      was associated with an increase in the magnitude of postoperative astigmatism in
      Groups I(WAS) and IV(WAS) (p<0.05), and with late suture removal in Group IV(WAS)
      (p<0.05). A decrease in the magnitude of post-suture removal astigmatism was
      associated with late suture removal in Groups I(WAS) and II(WAS). A logistic
      regression analysis showed that the prevalence of post-suture removal astigmatism
      axis shift was associated with increased corneal tunnel length, decreased
      magnitude of postoperative astigmatism, and early suture removal. CONCLUSIONS: In
      order to reduce postoperative and post-suture removal astigmatism, we recommend a
      short corneal tunnel length and late suture removal in patients with Group I(WAS)
      characteristics, late suture removal in Group II(WAS)-like patients, long corneal
      tunnel length in Group III(WAS)-like patients, and long corneal tunnel length and
      early suture removal in patients with characteristics of Group IV(WAS).

PMID- 20046683
TI  - The clinical course of the idiopathic epiretinal membrane after surgery.
AB  - PURPOSE: To evaluate the clinical course of visual acuity and foveal thickness in
      the idiopathic epiretinal membrane (ERM) after a vitrectomy with the use of
      triamcinolone. METHODS: We retrospectively reviewed the records of 30 patients
      (30 eyes) with ERM that were treated by vitrectomy from 2004 to 2008. Visual
      acuity and foveal thickness from optical coherence tomography imaging was
      obtained preoperatively and at every postoperative follow-up visit. RESULTS:
      Visual acuity improved by two or more lines of vision in 30%, 50%, 60%, and 70%,
      and stayed the same within +/-1 line in 47%, 50%, 40%, and 30% at one month,
      three months, five months, and seven months after surgery. Twenty-three percent
      of the subjects deteriorated by two or more lines of vision within one month
      after surgery. None of the subjects had reduced vision three months after
      surgery. Foveal thickness decreased significantly after surgery. The mean
      thickness was 409.7+/-107.9 microm before surgery and 288.6+/-66.1 microm seven
      months after surgery. Parameters which were significantly correlated with the
      final visual acuity included preoperative visual acuity (0.683), preoperative
      foveal thickness (0.544), and final foveal thickness (0.643) (p<0.005).
      CONCLUSIONS: Foveal thickness and visual acuity improved until seven months after
      the vitrectomy in patients with idiopathic ERM. Preoperative visual acuity,
      foveal thickness, and final foveal thickness had a significant correlation with
      the final visual acuity.

PMID- 20046684
TI  - The efficacy of fluid-gas exchange for the treatment of postvitrectomy retinal
      detachment.
AB  - PURPOSE: This study was designed to evaluate the efficacy of fluid-gas exchange
      for the treatment of postvitrectomy retinal detachment. METHODS: We
      retrospectively reviewed the records of 33 consecutive patients (35 eyes) who
      underwent fluid-gas exchange treatment for postvitrectomy retinal detachment
      using the two-needle pars plana approach technique. RESULTS: The retinal
      reattachment rate was 80.0% after complete intravitreal gas disappearance
      following the fluid-gas exchange; the overall success rate was 65.7%. Visual
      acuity was improved or stable in 80.0% of cases; a two-line or greater vision
      improvement or a best-corrected visual acuity of 0.4 or better occurred in 62.9%
      of cases. The success rates for superior retinal detachments and posterior pole
      retinal detachments were 76.5% and 85.7%, respectively. CONCLUSIONS: Fluid-gas
      exchange represents a simple and cost-effective alternative outpatient procedure
      for retinal reattachment without reoperation for the treatment of superior and
      posterior pole retinal detachments.

PMID- 20046685
TI  - Comparison between intravitreal bevacizumab and triamcinolone for macular edema
      secondary to branch retinal vein occlusion.
AB  - PURPOSE: To compare the effects of intravitreal bevacizumab to those of
      triamcinolone acetonide injection for the treatment of macular edema secondary to
      branch retinal vein occlusion. METHODS: This retrospective study included 50 eyes
      of 50 patients who received a single injection of intravitreal bevacizumab (1.25
      mg/0.05 mL, 22 eyes) or triamcinolone acetonide (4 mg/0.1 mL, 28 eyes) as the
      only treatment for macular edema secondary to branch retinal vein occlusion; all
      patients had a post-injection follow-up duration of >24 weeks. Best corrected
      visual acuity (BCVA), intraocular pressure (IOP), and central macular thickness
      (CMT) by optical coherence tomography were measured for up to 24 weeks after
      injection. RESULTS: BCVA was improved at 1, 4, 8,12 weeks post-injection in the
      bevacizumab group, and at 1, 4, 8 weeks post-injection in the triamcinolone
      group. No significant difference was found between the two groups except at 12
      weeks. CMT decreased significantly within each group, and no significant
      difference between groups was found. In the bevacizumab group, no elevated IOP
      was observed, whereas IOP was significantly increased at 4, 8, and 12 weeks after
      triamcinolone injection; IOP was therefore significantly different between the
      two groups. CONCLUSIONS: Intravitreal bevacizumab is a comparatively simple
      treatment method that can effectively improve BCVA and reduce CMT without ocular
      and systemic complications. Consequently, intravitreal bevacizumab injections may
      be useful as both an alternative and primary treatment for macular edema
      secondary to branch retinal vein occlusion.

PMID- 20046686
TI  - Effects of an intravitreal bevacizumab injection combined with panretinal
      photocoagulation on high-risk proliferative diabetic retinopathy.
AB  - PURPOSE: To investigate the short-term effects of panretinal photocoagulation
      (PRP) combined with an intravitreal injection of Avastin(bevacizumab) as an
      adjuvant to high-risk proliferative diabetic retinopathy (PDR). METHODS: The data
      was collected retrospectively from the eyes of high-risk PDR patients, which were
      divided into two groups. One eye was treated with only PRP (PRP only group) and
      the fellow eye of same patient was treated with both PRP and intravitreal
      bevacizumab injection (Adjuvant group). Best corrected visual acuity (BCVA), IOP
      (intraocular pressure), and new vessel (NV) size in fluorescein angiography were
      recorded immediately and at the six-week follow-up visit. Adverse events
      associated with intravitreal injection were investigated. RESULTS: Of 12 patients
      with high-risk PDR, five were male and seven were female. There were no
      statistically significant BCVA or IOP changes after treatment in either group
      (p=0.916, 0.888). The reduction of NV size was found in both groups, but NV size
      in the adjuvant group showed a greater decrease than that of the PRP only group
      (p=0.038). Three patients had adverse events after intravitreal injection. Two
      patients had mild anterior uveitis and one patient had a serious complication of
      branched retinal artery obstruction (BRAO). CONCLUSIONS: Intravitreal bevacizumab
      injection with PRP resulted in marked regression of neovascularization compared
      with PRP alone. One serious side effect, BRAO, was noted in this study. Further
      studies are needed to determine the effect of repeated intravitreal bevacizumab
      injections and the proper number of bevacizumab injections as an adjuvant.

PMID- 20046687
TI  - Analgesic effects of tramadol during panretinal photocoagulation.
AB  - PURPOSE: To evaluate the effectiveness of tramadol for the reduction of pain in
      panretinal photocoagulation (PRP). METHODS: A double-masked randomized controlled
      study was performed. Fifty-eight eyes in 29 patients with proliferative diabetic
      retinopathy were enrolled. The eyes of the patients were randomized into two
      groups. Group A received an empty capsule. Group B received an oral intake of 100
      mg tramadol. The capsule used in Group A had the same appearance as that used in
      Group B. Pain during PRP was assessed using a visual analog scale. Vital signs,
      including blood pressure and heart rate, were measured. RESULTS: The mean pain
      scores for groups A and B were 4.80+/-2.10 and 3.83+/-1.82 (p=0.09). There were
      no significant differences in the mean pain scores between the two groups. More
      patients in group A complained of greater pain than moderate intensity (visual
      analogue scale=4). Systemic blood pressure increased significantly in group A
      after laser treatment. However, there were no significant differences in the
      diastolic blood pressure changes between the two groups. We found no statistical
      correlation in the heart rate changes. CONCLUSIONS: We failed to prove that
      tramadol is effective for pain relief because of the small sample size. However,
      tramadol was effective for the relief of more severe pain. It was also found to
      stabilize vital sign changes, such as systolic blood pressure during PRP.

PMID- 20046688
TI  - Comparison of the stability of postoperative alignment in sensory exotropia:
      adjustable versus non-adjustable surgery.
AB  - PURPOSE: To compare the success rates and stabilities of postoperative alignment
      between adjustable and the non-adjustable surgeries in the treatment of sensory
      exotropia. METHODS: A retrospective analysis was performed on all patients with
      sensory exotropia who had undergone unilateral lateral rectus recession and
      medial rectus resection (R&R) between January 1998 and August 2005. Thirty-four
      patients underwent conventional R&R, and 20 patients underwent R&R with
      adjustable suture of the lateral rectus. The surgical results between the two
      groups were analyzed with regard to the preoperative and post-operative deviation
      angles and the postoperative drift. The postoperative deviation angle was
      measured on postoperative day 1 as well as at two weeks, three months, six months
      and the final visit after surgery. RESULTS: There were no statistically
      significant differences in the mean preoperative and postoperative deviation
      angles between the two groups. In 30 (88%) patients in the non-adjustable group
      and 15 (75%) patients in the adjustable group, postoperative deviation was less
      than 15 prism diopters (PD) at the three month follow-up. There was no
      significant difference in the mean postoperative drift between the two groups.
      CONCLUSIONS: Strabismus surgery with adjustable sutures did not show a
      significantly better result than surgery without adjustable sutures in the
      treatment of sensory exotropia. Considering the amount of postoperative exodrift
      in both groups, we postulate that the immediate ocular alignment after surgery
      for sensory exotropia should be orthophoric or 5-6 PD of esodeviation.

PMID- 20046690
TI  - Prognostic factors for the success of laser iridotomy for acute primary angle
      closure glaucoma.
AB  - PURPOSE: To identify the prognostic factors for successful laser iridotomy for
      acute angle-closure glaucoma (AACG). METHODS: We retrospectively reviewed the
      medical records of 77 eyes of 77 patients with AACG with initial intraocular
      pressure (IOP) above 40 mmHg. All of the patients received maximum tolerable
      medical therapy (MTMT) followed by laser iridotomy. In order to comparatively
      analyze the factors affecting successful laser iridotomy, an increase in IOP on
      follow-up was defined as increase in IOP greater than 21 mmHg requiring medical
      or surgical treatment. RESULTS: Successful laser iridotomy was achieved in 59.7%
      (46/77 eyes). Thirty-one eyes (40.3%) exhibited increased IOP on follow-up, and
      of these, 30 eyes developed an increase in IOP within six months after the first
      attack. The success rate was higher (92.9%) in 42 patients who had greater than
      30% IOP reduction by MTMT at the first attack compared to the 35 patients whose
      IOP reduction was less than 30%, of which 24 eyes (72.7%) showed more than 30%
      IOP reduction after intravenous hyperosmotic agent treatment (p=0.012). The
      success rate was higher in patients treated within seven days after the
      development of symptoms than in those treated after seven days (Odds ratio, 4.51;
      95% confidence interval, 1.38 to 14.75). CONCLUSIONS: Our data suggest that we
      can expect successful IOP control after laser iridotomy in eyes with AACG if the
      patient can be treated within seven days after the development of symptoms and if
      the IOP reduction was more than 30% by MTMT.

PMID- 20046689
TI  - Effect of excision of avascular bleb and advancement of adjacent conjunctiva for
      treatment of hypotony.
AB  - PURPOSE: To evaluate the efficacy of excision of avascular bleb and advancement
      of adjacent conjunctiva (EBAC) for treatment of hypotony after trabeculectomy
      with mitomycin C (MMC). METHODS: Fifteen patients (17 eyes) who received EBAC for
      correction of hypotony between September 1996 and October 2008 were reviewed
      retrospectively. The main outcomes were intraocular pressure (IOP) and
      postoperative complications. RESULTS: Hypotony (IOP <6 mmHg) of eight eyes
      (47.1%, seven patients) was caused by bleb perforation. Of these, two eyes (two
      patients) had a history of trauma. Hypotony appeared at 33.9+/-30.8 months, and
      EBAC was performed at 48.2+/-35.3 months after trabeculectomy with MMC. The mean
      follow-up period was 38.3+/-29.8 months. The qualified success rate of EBAC was
      100% at 51 months after EBAC, and the complete success rate of EBAC was 76.5% at
      six months and 70.6% at 51 months, as determined by Kaplan-Meier analysis. Post
      EBAC complications included blepharoptosis in four eyes (23.5%) and bleb
      perforation in one (5.9%). The blepharoptosis resolved within one month after
      EBAC in two patients. However, in the other patients, mild blepharoptosis
      remained at 17 and 22 months postoperatively. CONCLUSIONS: EBAC was found to be
      an effective method for treatment of hypotony after trabeculectomy with MMC, and
      postoperative blepharoptosis was a major complication.

PMID- 20046691
TI  - A pharmacologic pupillary test in the diagnosis of diabetic autonomic neuropathy.
AB  - PURPOSE: To screen for diabetic autonomic neuropathy of the pupil using 0.5%
      apraclonidine and 0.1% pilocarpine and to evaluate the early diagnostic value of
      this pharmacologic pupillary test by assessing the relationship between pupillary
      and cardiovascular autonomic neuropathies. METHODS: A total of 22 diabetic
      patients were recruited. Baseline pupillary diameter (PD) and the difference in
      PD between the test eye and the control eye before and after instillation of
      apraclonidine and pilocarpine were measured. All patients also underwent
      cardiovascular autonomic function (CAF) testing. RESULTS: Baseline PD in room
      light correlated with duration of diabetes mellitus (DM, p=0.049) and the
      presence of DM retinopathy (DMR, p=0.022). Eleven patients (50%) had positive
      apraclonidine tests, and two patients had positive pilocarpine tests. The
      patients who had positive pilocarpine tests also had positive apraclonidine
      tests. Patients who had a positive pupillary test had a significantly higher rate
      of positive CAF tests (p=0.032). CONCLUSIONS: Pupillary autonomic neuropathy was
      related to the duration of diabetes and the degree of DMR. There was also a
      significant correlation between pupillary autonomic neuropathy and cardiovascular
      autonomic neuropathy (CAN). Also, sympathetic nerve dysfunction occurred prior to
      parasympathetic dysfunction in this study. A simple pharmacologic pupillary test
      can help manage complications in diabetic patients because patients with
      pupillary autonomic dysfunction have an increased risk of CAN.

PMID- 20046692
TI  - A study of the vascular network of the iris using flat preparation.
AB  - PURPOSE: This study was performed to examine the vascular network of the human
      iris using flat preparation. METHODS: The ciliary body-iris structures were
      separated from human eyeballs, and a portion of the irises were treated with
      trypsin to remove the pigment granules. These iris tissues were unfolded and
      placed onto glass slides using flat preparation, and the vascular network of each
      iris was examined by fluorescein microscopy. The ciliary body-iris structures
      separated from the remaining eyes were stained with hematoxylin-eosin without
      trypsin treatment and were examined by light microscopy. RESULTS: The long
      posterior ciliary artery formed several branches before entering the iris root,
      and such branches formed the major arterial circle of the iris with diverse
      diameters in the vicinity of the iris root and the ciliary process. In the
      pupillary margin, the iris vasculature network formed a cone shape and then
      formed an arcade by connecting to adjacent vasculatures. In the vicinity of the
      collarette, the iris vasculature network formed the minor arterial circle of the
      iris with diverse diameters perpendicular to the arcade of the iris network
      located in the pupillary margin. In the pupillary margin, the capillaries were
      somewhat thick and connected to the irregular traveling iris vein. CONCLUSIONS:
      The above findings explain the human iris vascular network and provide a
      theoretical basis for the sectoral filling of the iris vasculature seen in
      fluorescein iris angiography.

PMID- 20046693
TI  - Trichilemmal carcinoma of the upper eyelid: a case report.
AB  - We report a very rare case of trichilemmal carcinoma (TLC) involving the upper
      eyelid. To the best of our knowledge, this is the first report of trichilemmal
      carcinoma of the upper eyelid in Korea. A 51-year-old man presented to our
      hospital complaining of a bloody discharge from his left upper eyelid. He had a
      soft and lobulated mass on the palpebral conjunctiva. An incisional biopsy
      revealed trabecular growth of tumor cells with clear cytoplasm, prominent
      nucleoli, frequent mitoses, and foci of trichilemmal keratinization.
      Immunohistochemically, the lesion was positive for p53 and negative for CD 34. A
      diagnosis of TLC was made, and total excision of the mass and reconstruction of
      the eyelid were performed. Trichilemmal carcinoma is a rare malignant tumor,
      though it appears to be an indolent neoplasm with no metastatic potential. The
      treatment of choice for trichilemmal carcinoma of the eyelid is complete excision
      with tumor-free margins due to the locally invasive nature of the lesion.

PMID- 20046694
TI  - Seborrheic keratosis of the conjunctiva: a case report.
AB  - Seborrheic keratosis is a benign epithelial neoplasia that occurs mainly in the
      skin of the eyelids and face. We describe a case of seborrheic keratosis of the
      conjunctiva confirmed by histopathology. A 72-year-old man presented with a
      recurrent conjunctival mass involving the nasal side of his right eye.
      Clinically, a diagnosis of conjunctival papilloma was made, and a mass excision
      was performed. The histopathological analysis evidenced a conjunctival-covering
      epithelium with papillomatous changes and irregular acanthosis, at the expense of
      a proliferation of basaloid cells. In addition, the lesion exhibited multiple
      pseudohorn cysts containing keratin. With the above findings, a diagnosis of
      conjunctival seborrheic keratosis was established. The occurrence of seborrheic
      keratosis on the conjunctiva is rare. In this case, seborrheic keratosis was
      confirmed by pathologic report despite its similar appearance with papilloma.
      Seborrheic keratosis should be considered in the differential diagnosis of
      conjunctival lesions.

PMID- 20046695
TI  - Refractive change caused silicone oil adhesion to the intraocular lens following
      Nd:YAG posterior capsulotomy.
AB  - A 32-year-old female who had undergone the silicone oil removal procedure
      presented with visual disturbance in her left eye. Several months previous, she
      had cataract surgery in a private clinic, and a month later she had a Nd:YAG
      laser procedure for posterior capsulotomy. The slit-lamp examination revealed
      silicone oil droplets that had adhered to the intraocular lens where the
      posterior capsulotomy was performed. She had experienced high myopia as a
      manifestation of the resulting refractive changes. We replaced the previous
      intraocular lens with a new acrylic intraocular lens with resulting improvement
      to her vision. Here we report the case of a female patient with a history of
      silicone oil removal surgery where the resulting silicone bubbles had not been
      removed thoroughly and remained in the vitreous cavity. These bubbles
      subsequently adhered to the intraocular lens following YAG laser posterior
      capsulotomy, resulting in refractive changes. We recommend that implanting a
      silicone intraocular lens in anyone with a history of the silicone oil removal
      procedure or who has a possible history of silicone oil use should be avoided.

PMID- 20046696
TI  - A case of retinal detachment in colobomatous macrophthalmos with microcornea
      syndrome.
AB  - We report a rare case of retinal detachment in colobomatous macrophthalmos with
      microcornea syndrome. A 25-year-old female who had suffered from poor vision in
      her left eye since early childhood and high myopia in her right eye (-11 D)
      visited our clinic because of a sudden deterioration of vision. Examination of
      the anterior segment showed microcornea with coloboma of the inferior pupil
      margin in the left iris. Fundus examination of the left eye revealed an inferior
      choroidal coloboma extending from the optic disc and macula. The patient also had
      total bullous retinal detachment. Pars plana vitrectomy with silicone oil
      tamponade was performed, and the retina was reattached. In the very rare
      condition of colobomatous macropthalmos with microcornea, retinal detachment may
      develop. Pars plana vitrectomy with additional silicone oil tamponade may be
      performed to treat this condition.

PMID- 20046697
TI  - Treatment of branch retinal artery occlusion with transluminal Nd:YAG laser
      embolysis.
AB  - The purpose of this paper was to report a successful treatment of transluminal
      Nd:YAG laser embolysis (NYE) for branch retinal artery occlusion (BRAO) with
      visible emboli. Two patients with acute, severe vision loss secondary to a branch
      retinal artery occlusion with visible emboli in one eye underwent NYE. A complete
      ocular examination was performed which included biomicroscopy of the posterior
      pole of the retina, intraocular pressure measurement, fundus color photographs,
      and fluorescein angiography (FA). After the NYE, the two patients showed dramatic
      improvements in best-corrected visual acuity, as well as, immediate and dramatic
      restorations in flow past the obstructed arteriole in FA. NYE is a treatment
      modality to be considered in patients with BRAO who present acutely with severe
      vision loss and a visible embolus.

PMID- 20046698
TI  - Valsalva retinopathy associated with an oratorical contest.
AB  - A 17-year-old man presented to us with a chief complaint of decreased visual
      acuity accompanied by central scotoma. There was nothing unusual in his medical
      history other than a recent oratorical contest. At the time of initial diagnosis,
      the corrected visual acuity was 20/20 in the right eye and 20/100 in the left
      eye. No significant findings were apparent on ophthalmic evaluation. On
      fundoscopy, there was a dumbbell-shaped macular bleed with a well-defined margin
      in the left eye. The clinical course was closely monitored along with drug
      therapy. Four weeks post presentation, the pre-retinal hemorrhage had nearly
      resolved. On fluorescein angiography, no significant findings were observed. In
      the left eye, the corrected visual acuity had improved to 20/25. Valsalva
      retinopathy is a pathology that occurs when a sudden increase in intra-thoracic
      pressure or abdominal pressure occurs in an otherwise healthy person. Here we
      report a case of Valsalva retinopathy occurring following an oratorical contest
      along with a review of the relevant literature.

PMID- 20046699
TI  - Bilateral endophthalmitis as the initial presentation of bacterial meningitis.
AB  - To report a case of bilateral endophthalmitis as the initial presentation of
      bacterial meningitis in a young, immunocompetent Korean patient. A 35-year-old
      female with a one day history of bilateral swollen eyes, visual disturbance,
      headache, petechial skin rash, and nausea visited our clinic. She was diagnosed
      as having endogenous endophthalmitis associated with bacterial meningitis.
      Intravenous broad spectrum antibiotic therapy was initiated with cefotaxime 3 g
      and ubacillin 3 g, four times daily. Intravitreal antibiotic (vancomycin 1 mg/0.1
      mL and ceftazidime 2 mg/0.1 mL) injections were performed in both eyes. Two weeks
      post presentation, the best corrected visual acuity in both eyes improved to 0.7,
      and inflammation of the anterior chamber and vitreous cavity was decreased. We
      recommend that when endogenous endophthalmitis is suspected along with
      meningitis, or if it is known to be present, intravitreal and intravenous
      antibiotics should be promptly administered to preserve vision.

PMID- 20046700
TI  - Acute lymphoblastic leukemia manifesting as acute Vogt-Koyanagi-Harada disease.
AB  - We describe a case of bilateral exudative retinal detachment associated with
      prodromal symptoms simulating the presentation of acute Vogt-Koyanagi-Harada
      disease that was eventually diagnosed as acute lymphoblastic leukemia. A 42-year
      old man presented with sudden visual loss in both eyes for two weeks. He
      complained of intermittent headache, neck stiffness and tinnitus for a month. His
      best-corrected visual acuities were 20/200 in both eyes. Fluorescein angiography,
      optical coherence topography and indocyanine green angiography featured bilateral
      serous retinal detachments. A clinical diagnosis of incomplete type Vogt-Koyanagi
      Harada disease was considered. However, complete blood cell count showed a marked
      increase in the number of white blood cells and bone marrow examination revealed
      precursor B cell lymphoblastic leukemia. The patient started on induction
      chemotherapy. A week later, his best-corrected visual acuities were 20/25 and the
      serous retinal detachments were nearly absorbed in both eyes. Bilateral exudative
      retinal detachment associated with neurologic and auditory abnormalities may be a
      presenting sign of acute lymphoblastic leukemia. Clinicians should be aware of
      the possibility of leukemia in such patients.

PMID- 20046701
TI  - A case of pseudo-Duane's retraction syndrome with old medial orbital wall
      fracture.
AB  - We report a case of pseudo-Duane's retraction syndrome with entrapment of the
      medial rectus muscle in an old medial orbital wall fracture presenting identical
      clinical symptoms as Duane's retraction syndrome. A 15-year-old boy presented
      with persistent limited right eye movement since a young age. Examination showed
      marked limited abduction, mildly limited adduction, and globe retraction
      accompanied by narrowing of the palpebral fissure during attempted adduction in
      the right eye. He showed a right esotropia of 16 prism diopters and his head
      turned slightly to the right. A slight enophthalmos was noted in his right eye. A
      computed tomography scan demonstrated entrapment of the medial rectus muscle and
      surrounding tissues in an old medial orbital wall fracture. A forced duction test
      revealed a marked restriction of abduction in the right eye. A 5 mm recession of
      the right medial rectus muscle was performed. Postoperatively, the patient's head
      turn and esotropia in the primary position were successfully corrected, but there
      was still some limitations to his ocular movement. The importance of several
      tests such as the forced duction test and an imaging study should be emphasized
      in making a diagnosis for limitation of eye movement.

PMID- 20046702
TI  - Liver x receptor: a novel therapeutic target.
AB  - The liver X receptors alpha and beta are orphan nuclear receptors that are key
      regulators in maintaining cholesterol homeostasis. Originally they were found to
      play an important role in reverse cholesterol transport, a pathway for the
      removal of excess cellular cholesterol. However several groups have now shown
      that the liver X receptors also functions in lipid and carbohydrate metabolism,
      cellular differentiation, apoptosis and many immune responses. Tissue
      distribution of the two paralogues differs with liver X receptor beta
      ubiquitously expressed, while liver X receptor alpha is confined to the liver,
      kidney, intestine, spleen, adipose tissue, macrophages and skeletal muscle. The
      endogenous ligands for the liver X receptors are certain oxidized derivatives of
      cholesterol, the oxysterols. Upon activation by oxysterols, the receptors form
      obligate heterodimers with retinoid X receptors alpha, beta and gamma; and become
      competent to activate the transcription of target genes.

PMID- 20046704
TI  - 3D-QSAR CoMFA study of some Heteroarylpyrroles as Possible Anticandida Agents.
AB  - A three dimensional quantitative structure-activity relationship study using the
      comparative molecular field analysis method was performed on a series of 3-aryl-4
      [alpha-(1H-imidazol-1-yl) aryl methyl] pyrroles for their anticandida activity.
      This study was performed using 40 compounds, for which comparative molecular
      field analysis models were developed using a training set of 33 compounds.
      Database alignment of all 33 compounds was carried out by root-mean-square fit of
      atoms and field fit of the steric and electrostatic molecular fields. The
      resulting database was analyzed by partial least squares analysis with cross
      validation; leave one out and no validation to extract optimum number of
      components. The analysis was then repeated with bootstrapping to generate the
      quantitative structure-activity relationship models. The predictive ability of
      comparative molecular field analysis model was evaluated by using a test set of 7
      compounds. The 3D- quantitative structure-activity relationship model
      demonstrated a good fit, having r(2) value of 0.964 and a cross validated
      coefficient r(2) value as 0.598. Further comparison of the coefficient contour
      maps with the steric and electrostatic properties of the receptor has shown a
      high level of compatibility and good predictive capability.

PMID- 20046703
TI  - Strategies for enhanced drug delivery to the central nervous system.
AB  - Treating central nervous system diseases is very challenging because of the
      presence of a variety of formidable obstacles that impede drug delivery.
      Physiological barriers like the blood-brain barrier and blood-cerebrospinal fluid
      barrier as well as various efflux transporter proteins make the entry of drugs
      into the central nervous system very difficult. The present review provides a
      brief account of the blood brain barrier, the P-glycoprotein efflux and various
      strategies for enhancing drug delivery to the central nervous system.

PMID- 20046705
TI  - Antiinflammatory, analgesic and antipyretic activity of certain thiazolidinones.
AB  - The thiazolidin-4-one derivatives and the corresponding spiro compounds were
      synthesized from sulphanilamide and were evaluated for anti-inflammatory and
      analgesic activity in acute and sub acute models. Compounds were also evaluated
      for antipyretic and cyclooxygenase enzyme inhibitory activity. All the compounds
      showed significant antiinflammatory, analgesic and antipyretic activity at 100
      mg/kg in all the models. The compounds B1, B2, B5, B6, and B8 showed maximum
      inhibition of COX-2 activity without inhibiting the COX-1 activity. The
      nimesulide was used as standard drug for comparison. The substitution at R, R(1)
      and R(2) with the functional groups Cl, OCH(3), NO(2) and OH in the aromatic ring
      resulted in increased activity as compared to unsubstituted thiazolidin-4-ones.
      However the substitution at R(3) with spiro group did not improve the activity.
      The study suggests that COX-2 binding site may not be a rigid structure but might
      adopt to various related molecules.

PMID- 20046706
TI  - Probable Mechanism(s) of Antifungal Activity of SJA-95, a Heptaene Polyene
      Antibiotic.
AB  - A new strain, streptomyces sp. S. 24 was isolated from a soil sample collected
      from Japan. The strain produced heptaene polyene antibiotic, SJA-95, in submerged
      culture and found to elicit promising antifungal activity against yeasts,
      filamentous fungi and clinical isolates, both in vitro and in vivo. Experimental
      studies were carried out using biological methods to understand the probable
      mechanism(s) of antifungal activity of SJA-95. Our experimental findings suggest
      that SJA-95 binds more avidly to ergosterol, the sterol in fungal cell membranes,
      than to cholesterol found in mammalian cell membranes. Such preferential binding
      of SJA-95 to ergosterol might help to establish its usefulness as a
      chemotherapeutic agent with lesser adverse reactions.

PMID- 20046707
TI  - Development of biodegradable starch microspheres for intranasal delivery.
AB  - Domperidone microspheres for intranasal administration were prepared by
      emulsification crosslinking technique. Starch a biodegradable polymer was used in
      preparation of microspheres using epichlorhydrine as cross-linking agent. The
      formulation variables were drug concentration and polymer concentration and batch
      of drug free microsphere was prepared for comparisons. All the formulations were
      evaluated for particle size, morphological characteristics, percentage drug
      encapsulation, equilibrium swelling degree, percentage mucoadhesion, bioadhesive
      strength, and in vitro diffusion study using nasal cell. Spherical microspheres
      were obtained in all batches with mean diameter in the range of above 22.8 to
      102.63 mum. They showed good mucoadhesive property and swelling behaviour. The in
      vitro release was found in the range of 73.11% to 86.21%. Concentration of both
      polymer and drug affect in vitro release of drug.

PMID- 20046708
TI  - Preparation and evaluation of buccoadhesive films of atenolol.
AB  - This paper describes the preparation of new bilayered device comprising a drug
      containing mucoadhesive layer and a drug free backing layer. Bilaminated films
      were produced by a casting/ solvent evaporation technique. The mucoadhesive layer
      was composed of mixture of drug and sodium alginate with or without carbopol 934
      P, and backing layer was made of ethyl cellulose. The double layer structure
      design was expected to provide drug delivery in a unidirectional fashion to the
      mucosa and avoid loss of drug due to wash out with saliva. The fabricated films
      were subjected to in vitro drug release, in vitro permeation through porcine
      buccal mucosa. The bilayered films were also evaluated for mucoadhesive strength,
      mucoadhesive time, folding endurance, hydration studies and tensile strength.

PMID- 20046709
TI  - Development of fast dispersible aceclofenac tablets: effect of functionality of
      superdisintegrants.
AB  - Aceclofenac, a non-steroidal antiinflammatory drug, is used for posttraumatic
      pain and rheumatoid arthritis. Aceclofenac fast-dispersible tablets have been
      prepared by direct compression method. Effect of superdisintegrants (such as,
      croscarmellose sodium, sodium starch glycolate and crospovidone) on wetting time,
      disintegration time, drug content, in vitro release and stability parameters has
      been studied. Disintegration time and dissolution parameters (t(50%) and t(80%))
      decreased with increase in the level of croscarmellose sodium. Where as,
      disintegration time and dissolution parameters increased with increase in the
      level of sodium starch glycolate in tablets. However, the disintegration time
      values did not reflect in the dissolution parameter values of crospovidone
      tablets and release was dependent on the aggregate size in the dissolution
      medium. Stability studies indicated that tablets containing superdisintegrants
      were sensitive to high humidity conditions. It is concluded that fast-dispersible
      aceclofenac tablets could be prepared by direct compression using
      superdisintegrants.

PMID- 20046710
TI  - Comparative molecular field analysis of benzothiazepine derivatives:
      mitochondrial sodium calcium exchange inhibitors as antidiabetic agents.
AB  - Mitochondrial sodium calcium exchange inhibitors are novel agents in the
      treatment of type-II diabetes due to their glucose dependent efficacy. While the
      compounds of this class are expected to correct hyperglycemia, they do not lower
      basal blood glucose level, thus avoiding the serious consequences of
      hypoglycemia. The 3DQSAR analysis of benzothiazepines and their derivatives as
      mitochondrial sodium calcium exchange inhibitors was performed by comparative
      molecular field analysis to determine the structural factors required for the
      activity of these compounds. After performing a leave one out cross validation
      study, satisfactory results were obtained, with cross-validated q(2) and
      conventional r(2) values of 0.711 and 0.970, respectively. The results provided
      the tools for predicting the affinity of the related compounds, and guidance for
      the designing and synthesis of novel and potent mitochondrial sodium calcium
      exchange inhibitors as antidiabetic agents.

PMID- 20046711
TI  - Albumin microspheres as an ocular delivery system for pilocarpine nitrate.
AB  - Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal
      denaturation process in the size range of 1-12 mum. A series of batches were
      prepared to study factors, which may affect the size and entrapment efficiency of
      drug in microspheres and optimized the process. Drug loaded microspheres so
      obtained were evaluated for their size, entrapment efficiency, release rate and
      biological response. Electron photomicrographs were taken (8000X) to study the
      morphological characteristics of microspheres. The entrapment and encapsulation
      of pilocarpine after process optimization was found to be 82.63% and 62.5%
      respectively. In vitro dissolution rate studies revealed that the release of drug
      from the microspheres followed spherical matrix mechanism. Biological response of
      microspheric suspension was measured by reduction in intraocular pressure in
      albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic
      parameters viz. onset of action, duration of action, Tmax and AUC were studied. A
      measurable difference was found in the mean miotic response, duration and AUC of
      pilocarpine nitrate microspheric suspension.

PMID- 20046712
TI  - Rapid and Simple RPHPLC Method for the Estimation of Metformin in Rat Plasma.
AB  - A simple reverse phase high-performance liquid chromatographic method has been
      developed for determining the concentration of metformin in rat plasma. The
      method employs C(18) column (300 mm x 2.4 mm i.d.), ammonium acetate (0.15 M) and
      acetonitrile (90:10; pH-5.5; 1.0 ml/min) as mobile phase and ultraviolet
      detection at 236 nm. Acetonitrile was used to simultaneously deproteinize rat
      plasma and extract metformin. The assay was linear in the concentration range of
      0.33 mug-16.6 mug/ml with co-efficient of correlation 0.994. The retention time
      was 4.7 min. The method was found to be precise (% CV < 15%), accurate and
      suitable for pharmacokinetic study of orally administered metformin in rats.

PMID- 20046713
TI  - Formulation and targeting efficiency of Cisplatin engineered solid lipid
      nanoparticles.
AB  - The present study is aimed at the overall improvement in the efficacy, reduced
      toxicity and enhancement of therapeutic index of cisplatin. Solid lipid
      nanoparticulate delivery system of cisplatin has been developed by
      microemulsification method by using stearic acid, soy lecithin 95% and sodium
      glycolate. The formulations were then characterized with respect to size and its
      surface morphology, zeta potential, entrapment efficiency, in vitro drug release
      profile, in vivo drug targeting studies and its stability under specific
      conditions. The formulated solid lipid nanoparticles were oval with a diameter
      ranging from 250 nm to 500 nm. The lowest entrapment efficiency was found to be
      47.59% and highest was found to be 74.53%. The zeta potential was in the range of
      -9.8 to -11.2 mv. In vitro release study was analyzed using various mathematical
      models. Highest cumulative percent drug release was observed with F-1 (97.22 %)
      and lowest with F-4 (78.43%) in 16 h. The in vivo result of formulated solid
      lipid nanoparticles of cisplatin reveals that the drug is preferentially
      targeting to liver followed by brain and lungs.

PMID- 20046714
TI  - Synthesis of novel indolyl-pyrimidine antiinflammatory, antioxidant and
      antibacterial agents.
AB  - A number of chalcones were synthesized by reacting indole-3-aldehyde, prepared by
      Vilsemeir Haack reaction with 4-substituted acetophenone in NaOH solution in
      ethanol. These chalcones were immediately reacted with urea, thiourea and
      guanidine hydrochloride in presence of concentrated hydrochloric acid as reagent
      to obtain the corresponding hydroxy, thio and amino pyrimidines. The synthesized
      heterocyclics were characterized on the basis of physical, chemical tests and
      spectroscopic data and were tested for the acute antiinflammatory activity,
      antioxidant, antibacterial activity using carragenan-induced rat paw oedema
      method, DPPH (diphenylpicrylhydrazyl) radical scavenging method and cup plate
      method using Muller-Hinton agar media respectively. Evaluation of the compounds
      revealed remarkable antiinflammatory activity reflected by their ability to
      reduce the carragenan-induced inflammation in rats, appreciable antioxidant
      activity and also antibacterial activity was observed.

PMID- 20046715
TI  - Studies on Indomethacin Intraocular Implants Using Different in vitro Release
      Methods.
AB  - Intra ocular implants of sodium alginate alone and in combination with
      hydroxypropylmethylcellulose with or without calcium chloride were formulated
      with indomethacin as a model drug. The drug release from the implants was
      evaluated using static method, continuous flow through apparatus (developed in
      house), USP dissolution and agar diffusion. Except in the static method,
      indomethacin particle size did not impart any effect on the drug release. In agar
      diffusion method, an increase in agar concentration from 1 to 2% resulted in a
      significant decrease (P< 0.005) in the amount of drug released. Inclusion of
      hydroxypropylmethylcellulose (33.3, 41.6 and 50% w/w), resulted in decrease of
      indomethacin release irrespective of the method of dissolution study. The agar
      diffusion method and the continuous flow through methods seem to simulate to a
      certain extent the in vivo conditions as far as the placement of the device and
      the hydrodynamic diffusion layer around the intra ocular implant is concerned.
      The static method and USP method affected the hydrodynamic diffusion layer either
      too slowly or too fast.

PMID- 20046716
TI  - Hydrolytic Degradation Profile and RP-HPLC Estimation of Cilostazol in Tablet
      Dosage Form.
AB  - A simple, selective, precise and stability-indicating high-performance liquid
      chromatographic method of analysis of cilostazol in pharmaceutical dosage form
      was developed and validated. The solvent system consisted of 10 mM phosphate
      buffer (pH 6.0):acetonitrile:methanol (20:40:40). Retention time of cilostazol in
      C18 column was 5.7 +/- 0.1 min at the flow rate 1.3 ml/min. Cilostazol was
      detected at 248 nm at room temperature. The linear regression analysis data for
      the calibration plots showed good linear relationship with correlation
      coefficient value, r( 2) =0.9998 in the concentration range 100-3200 ng/ml with
      slope 43.45 intercept 156.75. The method was validated for linearity, range,
      accuracy, precision and specificity. Cilostazol was determined in tablet dosage
      form in range of 99.58-100.67% with 0.4600 standard deviation. Stress studies
      were conducted in acid and alkali hydrolysis with gradual increasing
      concentration. Cilostazol was found to be stable in various concentrations of
      acidic and alkaline.

PMID- 20046717
TI  - Formulation and in vitro Evaluation of Floating Capsules of Theophylline.
AB  - Sustained release floating capsules for theophylline were fabricated using
      drug:polymer ratio of 30:70. The hydrocolloids were used in different proportions
      and four formulations were prepared. These formulations were optimized on the
      basis of buoyancy, matrix integrity, duration of floating and in vitro drug
      release. All the four formulations showed good buoyancy and matrix integrity. The
      duration of floating was more than 12 h for all formulations. In vitro drug
      release study of these formulations indicated controlled release of theophylline
      and about 76 percent drug was released at the end of 12 h.

PMID- 20046718
TI  - Antihyperglycemic Activity of Various Fractions of Cassia auriculata Linn. in
      Alloxan Diabetic Rats.
AB  - Present work describes the potent antidiabetic fraction from flowers of Cassia
      auriculata Linn. Hydromethanolic extract along with its ethyl acetate and n
      butanol fractions were evaluated for antidiabetic activity in alloxan-induced
      diabetes in rats. The n-butanol fraction exhibited significant reduction
      (p<0.001) in blood glucose levels and was also found effective in restoring the
      blood lipids and proteins to normal level. The activity was found comparable with
      standard drug phenformin. The hydromethanolic extract and its fractions were
      subjected to preliminary qualitative chemical investigations which indicated the
      presence of phenolic compounds, carbohydrates, tannins, steroids and amino acids.

PMID- 20046719
TI  - Herb-drug interaction: a case study of effect of ginger on the pharmacokinetic of
      metronidazole in rabbit.
AB  - The effect of ginger on the pharmacokinectic of metronidazole was studied using
      rabbits in a crossover study method. The relevance of this study borders on the
      wide use of ginger for culinary and phytotherapeutic purposes, and metronidazole
      that is commonly used for every gastrointestinal complain in our communities
      without prescription. Ginger significantly increased the absorption and plasma
      half-life, and significantly decreased the elimination rate constant and
      clearance of metronidazole (P<0.05). Thus, in clinical practice, the patients
      should be advised on the serious implication of using both items together.

PMID- 20046720
TI  - Development and validation of a HPTLC method for Estimation of Duloxetine
      Hydrochloride in Bulk Drug and in Tablet Dosage Form.
AB  - Duloxetine hydrochloride is a potent dual reuptake inhibitor of serotonin and
      norepinephrine used to treat major depressive disorders. The present work
      describes a simple, precise and accurate HPTLC method for its estimation as bulk
      and in tablet dosage form. The chromatographic separation was carried out on
      precoated silica gel 60 F254 aluminium plates using mixture of
      chloroform:methanol (8:1 v/v) as mobile phase and densitometric evaluation of
      spots was carried out at 235 nm using Camag TLC Scanner-3 with win CAT 1.3.4
      version software. The experimental parameters like band size of the spot applied,
      chamber saturation time, solvent front migration, slit width etc. were critically
      studied and optimum conditions were evolved. The drug was satisfactorily resolved
      with Rf value 0.11+/-0.01. The accuracy and reliability of the proposed method
      was ascertained by evaluating various validation parameters like linearity (40
      200 ng/spot), precision (intra-day RSD 0.46-0.75%, inter-day RSD 0.46-1.59%),
      accuracy (98.72+/-0.20) and specificity according to ICH guidelines. The proposed
      method can analyse ten or more formulation units simultaneously on a single plate
      and provides a faster and cost-effective quality control tool for routine
      analysis of duloxetine hydrochloride as bulk drug and in tablet formulation.

PMID- 20046721
TI  - Simultaneous UV Spectrophotometric Estimation of Ambroxol Hydrochloride and
      Levocetirizine Dihydrochloride.
AB  - A novel, simple, sensitive and rapid spectrophotometric method has been developed
      for simultaneous estimation of ambroxol hydrochloride and levocetirizine
      dihydrochloride. The method involved solving simultaneous equations based on
      measurement of absorbance at two wavelengths 242 nm and 231 nm, the gamma max of
      ambroxol hydrochloride and levocetirizine dihydrochloride, respectively. Beer's
      law was obeyed in the concentration range 10-50 mug/ml and 8-24 mug/ml for
      ambroxol hydrochloride and levocetirizine dihydrochloride respectively. Results
      of the method were validated statistically and by recovery studies.

PMID- 20046722
TI  - Antibacterial potential assessment of jasmine essential oil against e. Coli.
AB  - The antibacterial activity of Jasmine (Jasminum sambac L.) flower hydro steam
      distilled essential oil, synthetic blends and six major individual components was
      assessed against Escherichia coli (MTCC-443) strain. The activity was
      bactericidal. Minimum inhibitory concentration was determined by tube dilution
      technique, and the Minimum inhibitory concentration ranged between 1.9-31.25
      mul/ml. Phenolcoefficient of the oil, synthetic blends and components varied
      between 0.6-1.7. The activity of the chemicals was possibly due to the inhibition
      of cell membrane synthesis.

PMID- 20046723
TI  - Hepatoprotective Activity of Vitex trifolia against Carbon Tetrachloride-induced
      Hepatic Damage.
AB  - Aqueous and ethanol extracts of leaf of Vitex trifolia was investigated for
      hepatoprotective activity against carbon tetrachloride induced liver damage. To
      assess the hepatoprotective activity of the extracts, various biochemical
      parameters viz., total bilirubin, total protein, alanine transaminase, aspartate
      transaminase and alkaline phosphatase activities were determined. Results of the
      serum biochemical estimations revealed significant reduction in total bilirubin
      and serum marker enzymes and increase in total protein in the animals treated
      with ethanol and aqueous extracts. However significant rise in these serum
      enzymes and decrease in total protein level was noticed in CCl4 treated group
      indicating the hepatic damage. The hepatoprotective activity is also supported by
      histological studies of liver tissue. Histology of the liver tissue treated with
      ethanol and aqueous extracts showed normal hepatic architecture with few fatty
      lobules. Hence the present study revealed that Vitex trifolia could afford
      significant protection against CCl(4) induced hepatocellular injury.

PMID- 20046724
TI  - Synthesis and evaluation of L-glutamic Acid analogs as potential anticancer
      agents.
AB  - Four N-(benzenesulfonyl)-L-glutamic acid bis(p-substituted phenylhydrazides) were
      synthesized and evaluated for anticancer activity in vitro in DU-145 and PC-3
      prostate cancer and in COLO-205 colon cancer cell lines by MTT assay. The analog
      with the nitro group substitution exhibited potent activity (% Inhibition 84.7
      and 72.0 in DU-145 and PC-3 respectively at 80 mug/ml concentration). Another
      series of substituted 1-(benzenesulfonyl)-5-oxopyrrolidine 2-carboxamides (11a-f)
      were synthesized and evaluated for anticancer activity in vitro in colon (COLO
      205), breast (Zr-75-1) and prostate (PC-3) cancer cell lines by MTT assay using
      adriamycin as standard. Test compounds 11a-c showed potent activity (% Inhibition
      61.2 to 79.2 at 20 mug/ml and 67.2 to 87.2 at 40 mug/ml) in PC-3 cell line which
      is superior to the activity of Adriamycin. In comparison compounds 11d-f were
      less potent. In Zr-75-1 cell line 11a-e showed % inhibition ranging from 32.4 to
      54.9 at 10 mug/ml concentration while in COLO-205 cell line 11a-f showed poor
      activity.

PMID- 20046725
TI  - Spectrophotometeric Determination of Cefuroxime Axetil from bulk and in its
      tablet dosage form.
AB  - A simple rapid spectrophotometric method has been developed for estimation of
      cefuroxime axetil from bulk drug and tablet dosage form by using 1-nitroso-2
      napthol and sodium hydroxide. The method is based on the formation of yellow
      orange coloured complex of drug with 1-nitroso-2-napthol having absorbance maxima
      at 424 nm. The Beer's law is obeyed in the concentration range of 10-50 mug/ml of
      the drug but more precisely it obeys in the range of 10- 30 mug/ml. The slope and
      intercept values are 0.0101 and 0.0838, respectively. Results of analysis of this
      method were validated statistically and by recovery studies. The method is
      applied to the marketed tablet formulation. Result of analysis of tablet
      formulation given as percentage of label claim +/-standard deviation is 99.17+/
      1.57. The precision and accuracy was examined by performing recovery studies and
      was found to be 99.50+/-1.82. Sandell's correlation coefficient is calculated as
      0.4434. The developed method is simple, sensitive and reproducible and can be
      used for routine analysis of cefuroxime axetil from bulk and tablet dosage form.

PMID- 20046726
TI  - Stability-indicating Simultaneous HPTLC Method for Olanzapine and Fluoxetine in
      Combined Tablet Dosage Form.
AB  - A rapid, selective and stability-indicating high performance thin layer
      chromatographic method was developed and validated for the simultaneous
      estimation of olanzapine and fluoxetine in combined tablet dosage form.
      Olanzapine and fluoxetine were chromatographed on silica gel 60 F(254) TLC plate
      using methanol:toluene (4:2 v/v) as the mobile phase and spectrodensitometric
      scanning-integration was performed at a wavelength of 233 nm using a Camag TLC
      Scanner III. This system was found to give compact spots for both olanzapine
      (R(f) value of 0.63+/-0.01) and fluoxetine (R(f) value of 0.31+/-0.01). The
      polynomial regression data for the calibration plots showed good linear
      relationship with r(2)=0.9995 in the concentration range of 100-800 ng/spot for
      olanzapine and 1000-8000 ng/spot for fluoxetine with r(2)=0.9991. The method was
      validated in terms of linearity, accuracy, precision, recovery and specificity.
      The limit of detection and the limit of quantification for the olanzapine were
      found to be 30 and 100 ng/spot, respectively and for fluoxetine 300 and 1000
      ng/spot, respectively. Olanzapine and fluoxetine were degraded under acidic,
      basic and oxidation degradation conditions which showed all the peaks of degraded
      product were well resolved from the active pharmaceutical ingredient. Both drugs
      were not further degraded after thermal and photochemical degradation. The method
      was found to be reproducible and selective for the simultaneous estimation of
      olanzapine and fluoxetine. As the method could effectively separate the drugs
      from their degradation products, it can be employed as a stability-indicating
      method.

PMID- 20046727
TI  - Effect of hydroxylpropyl-beta-cyclodextrin on Solubility of Carvedilol.
AB  - The present study was undertaken to examine the effect of pH and concentration of
      hydroxypropyl-beta-cyclodextrin on the solubility of carvedilol as it shows pH
      dependent solubility. The equilibrium solubility of carvedilol in a series of
      solutions of varying pH (from 1.2 to 11) was determined and compared with the
      equilibrium solubility of carvedilol in the presence of 20% hydroxypropyl-beta
      cyclodextrin at same pH values. It was observed that solubility of protonated
      form is more than neutral molecule. Hydroxypropyl-beta-cyclodextrin resulted in
      increased solubility at all the pH. But inclusion in the cavity of hydroxypropyl
      beta-cyclodextrin might depend upon charge state of the molecule. So it can be
      concluded that solubility of carvedilol, can be increased either by the addition
      of hydroxypropyl-beta-cyclodextrin or by adding pH lowering agents. But both
      these methods if are to be used together, pH should be selected carefully.

PMID- 20046728
TI  - UV and Three Derivative Spectrophotometric Methods for Determination of Ezetimibe
      in Tablet Formulation.
AB  - UV, first, second and third derivative spectrophotometric methods have been
      developed for the determination of ezetimibe in pharmaceutical formulation. The
      solutions of standard and sample were prepared in methanol. For the first method,
      UV spectrophotometry, the quantitative determination of the drug was carried at
      233 nm and the linearity range was found to be 6-16 mug/ml. For the first, second
      and third derivative spectrophotometric methods the drug was determined at 259.5
      nm, 269 nm and 248 nm with the linearity ranges 4-14 mug/ml, 4-14 mug/ml and 4-16
      mug/ml. The calibration graphs constructed at their wavelength of determination
      were found to be linear for UV and derivative spectrophotometric methods. All the
      proposed methods have been extensively validated. The described methods can be
      readily utilized for the analysis of pharmaceutical formulation. There was no
      significant difference between the performance of the proposed methods regarding
      the mean values and standard deviations.

PMID- 20046729
TI  - Kinetics of Autoxidation of an Oil Extract from Terminalia catappa.
AB  - Soxhlet extractor was used in the extraction of oil from milled seeds of
      Terminalia catappa using petroleum ether (40-60 degrees ). The optimal oil yield
      was 56.71+/-1.66% with a viscosity of 40.79+/-1.05 centipoises. Other parameters
      of the oil were found as follows; specific gravity-0.9248, refractive index
      1.4646, acid value-3.35, peroxide value-8.6, saponification value-166.2, and
      unsaponifiable matter-1.46. The crude oil extract was water-degummed, bleached
      and deodorized to generate what we called refined oil. Autoxidation of the crude
      and refined T. catappa oil extract was done at five different temperatures of 0+/
      0.1 degrees , 20+/-0.1 degrees , 40+/-0.1 degrees , 60+/-0.1 degrees and 80+/-0.1
      degrees and also in the presence of pure alpha-tocopherol at a concentration of
      1.0% (w/v) by measuring peroxide value variations over 96 h. In all evaluations,
      the refined oil exhibited lower tendency towards autoxidation but not at
      temperatures above 60+/-0.1 degrees . The use of Arrhenius equation revealed
      generally very low activation energies of 0.0261 cal/degxmol and
      0.0122cal/degxmol for crude oil and antioxidant-treated crude oil, respectively
      and 0.0690 cal/degxmol and 0.0177 cal/degxmol for the refined oil. This study
      indicates T. catappa seed oil to be potential pharmaceutical oil with excellent
      characteristics.

PMID- 20046730
TI  - Development and Validation of RP-HPLC Method for Simultaneous Estimation of
      Atorvastatin Calcium and Fenofibrate in Tablet Dosage Forms.
AB  - A reverse phase high performance liquid chromatographic method was developed for
      the simultaneous estimation of atorvastatin calcium and fenofibrate in tablet
      formulation. The separation was achieved by Luna C18 column and methanol:acetate
      buffer pH 3.7 (82:18 v/v) as mobile phase, at a flow rate of 1.5 ml/min.
      Detection was carried out at 248 nm. Retention time of atorvastatin calcium and
      fenofibrate was found to be 3.02+0.1 and 9.05+0.2 min, respectively. The method
      has been validated for linearity, accuracy and precision. Linearity for
      atorvastatin calcium and Fenofibrate were in the range of 1-5 mug/ml and 16-80
      mug/ml, respectively. The mean recoveries obtained for Atorvastatin calcium and
      fenofibrate were 101.76% and 100.06%, respectively. Developed method was found to
      be accurate, precise, selective and rapid for simultaneous estimation of
      atorvastatin calcium and fenofibrate in tablets.

PMID- 20046731
TI  - Development and evaluation of hepatoprotective polyherbal formulation containing
      some indigenous medicinal plants.
AB  - The present study explores the hepatoprotective activity of various extracts of
      Ferula asafoetida, Momordica charantia Linn and Nardostachys jatamansi against
      experimental hepatotoxicity. Polyherbal suspensions were formulated using
      extracts showing significant activity and evaluated for both physicochemical and
      hepatoprotective activity in comparison with LIV-52 as standard. Petroleum ether
      (60-80 degrees ), chloroform, benzene, ethanol and aqueous extracts of Ferula
      asafetida, Momordica charantia Linn and Nardostachys jatamansi were evaluated for
      hepatoprotective activity against carbon tetrachloride-induced liver toxicity in
      Wistar rats. Polyherbal suspensions were prepared by the trituration method using
      a suspending agent and other excipients. Formulation F3 has shown significant
      hepatoprotective effect by reducing the elevated serum enzyme levels such as
      glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline
      phosphatase. These biochemical observations were supplemented by
      histopathological examination of liver sections. Various parameters evaluated for
      all formulations were within the official specifications. Experimental data
      suggested that treatment with formulation F3 enhances the recovery from carbon
      tetra chloride-induced hepatotoxicity. From these results it may be concluded
      that the F3 formulation (containing chloroform, petroleum ether and aqueous
      extracts of Ferula asafetida, petroleum ether and ethanol extracts of Momordica
      charantia Linn. and petroleum ether and ethanol extracts of Nardostachys
      jatamansi) demonstrated significant hepatoprotective activity, that might be due
      to combined effect of all these extracts.

PMID- 20046732
TI  - Protein and Peptide drug delivery: oral approaches.
AB  - Till recent, injections remained the most common means for administering
      therapeutic proteins and peptides because of their poor oral bioavailability.
      However, oral route would be preferred to any other route because of its high
      levels of patient acceptance and long term compliance, which increases the
      therapeutic value of the drug. Designing and formulating a polypeptide drug
      delivery through the gastro intestinal tract has been a persistent challenge
      because of their unfavorable physicochemical properties, which includes enzymatic
      degradation, poor membrane permeability and large molecular size. The main
      challenge is to improve the oral bioavailability from less than 1% to at least 30
      50%. Consequently, efforts have intensified over the past few decades, where
      every oral dosage form used for the conventional small molecule drugs has been
      used to explore oral protein and peptide delivery. Various strategies currently
      under investigation include chemical modification, formulation vehicles and use
      of enzyme inhibitors, absorption enhancers and mucoadhesive polymers. This review
      summarizes different pharmaceutical approaches which overcome various
      physiological barriers that help to improve oral bioavailability that ultimately
      achieve formulation goals for oral delivery.

PMID- 20046734
TI  - Immunological studies on the aerial roots of the Indian banyan.
AB  - The aqueous extract of the aerial roots the Indian Banyan, Ficus benghalensis L.
      (Family: Moraceae) was evaluated for its effect on both specific and non-specific
      immunity. This extract exhibited a significant increase in percentage
      phagocytosis by human neutrophils in the in vitro tests. It exhibited promising
      immunostimulant activity at doses of 50, 100, 200 and 400 mg/kg body weight in
      SRBC induced hypersensitivity reaction and hemagglutination reaction in rats. The
      aqueous extract was found to stimulate the cell mediated and antibody mediated
      immune responses.

PMID- 20046733
TI  - Recent challenges in insulin delivery systems: a review.
AB  - Relatively, a large percentage of world population is affected by diabetes
      mellitus, out of which approximately 5-10% with type 1 diabetes while the
      remaining 90% with type 2. Insulin administration is essential for type 1
      patients while it is required at later stage by the patients of type 2. Current
      insulin delivery systems are available as transdermal injections which may be
      considered as invasive. Several non-invasive approaches for insulin delivery are
      being pursued by pharmaceutical companies to reduce the pain, and hypoglycemic
      incidences associated with injections in order to improve patient compliance.
      While any new insulin delivery system requires health authorities' approval, to
      provide long term safety profile and insuring patients' acceptance. The
      inhalation delivery system Exubera((R)) has already become clinically available
      in the United States and Europe for patients with diabetes as non-invasive
      delivery system.

PMID- 20046735
TI  - Modulation of venlafaxine hydrochloride release from press coated matrix tablet.
AB  - The aim of present study was to prepare novel modified release press coated
      tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and
      hydroxypropylmethylcellulose K100M were used as release modifier in core and
      coat, respectively. A 3(2) full factorial design was adopted in the optimization
      study. The drug to polymer ratio in core and coat were chosen as independent
      variables. The drug release in the first hour and drug release rate between 1 and
      12 h were chosen as dependent variables. The tablets were characterized for
      dimension analysis, crushing strength, friability and in vitro drug release. A
      check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat
      respectively, was prepared. The tablets of check point batch were subjected to in
      vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The
      kinetics of drug release was best explained by Korsmeyer and Peppas model
      (anomalous non-Fickian diffusion). The systematic formulation approach enabled us
      to develop modified release venlafaxine hydrochloride tablets.

PMID- 20046736
TI  - Exploration of cold extrusion for the preparation of enteric minitablets of
      isoniazid.
AB  - The objective of the present work was to formulate the enteric minitablets of
      isoniazid by cold extrusion method. The minitablets were prepared using
      isoniazid, hydroxylpropylmethylcellulose phthalate and dibasic calcium phosphate.
      The minitablets were coated using hydroxypropylmethylcellulose phthalate. Full
      factorial design was adopted to optimize the formulation. The minitablets showed
      good flow and acceptable friability. The drug release was resisted in 0.1 N HCl
      for 2 h from the optimized batch. The optimized batch showed more than 90% of
      drug release in phosphate buffer in 15 min. Capsules containing rifampicin powder
      and enteric isoniazid minitablets showed complete drug release in acidic and
      alkaline media respectively. The process of cold extrusion appears to be an
      attractive alternative to by-pass the existing patents.

PMID- 20046737
TI  - Development and characterization of polymeric microspheres for controlled release
      protein loaded drug delivery system.
AB  - The aim of the present work was to investigate the preparation of microspheres as
      potential drug carriers for proteins, intended for controlled release
      formulation. The hydrophilic bovine serum albumin was chosen as a model protein
      to be encapsulated within poly(D,L-lactide-co-glycolide) (50:50) microspheres
      using a w/o/w double emulsion solvent evaporation method. Different parameters
      influencing the particle size, entrapment efficiency and in vitro release
      profiles were investigated. The microspheres prepared with different molecular
      weight and hydrophilicity of poly(D,L-lactide-co-glycolide) polymers were non
      porous, smooth surfaced and spherical in structure under scanning electron
      microscope with a mean particle size ranging from 3.98 to 8.74 mum. The protein
      loading efficiency varied from 40 to 71% of the theoretical amount incorporated.
      The in vitro release profile of bovine serum albumin from microspheres presented
      two phases, initial burst release phase due to the protein adsorbed on the
      microsphere surface, followed by slower and continuous release phase
      corresponding to the protein entrapped in polymer matrix. The release rate was
      fairly constant after an initial burst release. Consequently, these microspheres
      can be proposed as new controlled release protein delivery system.

PMID- 20046738
TI  - The Electrospray Ionization - Mass Spectra of Erythromycin A Obtained from a
      Marine Streptomyces sp. Mutant.
AB  - In our ongoing search for production improvements of bioactive secondary
      metabolites from marine Streptomyces through the induction of mutations using UV
      light, out of 145 isolates, mutant 10/14 was able to produce potent antibacterial
      metabolites other than the parent strain as established by chromatographic
      analysis. Up-scaling fermentation of mutant 10/14, followed by working up and
      isolation delivered five metabolites, phenazine, 1-acetyl-beta -carboline,
      perlolyrin and erythromycin A, along with an oily substance. The latter two
      compounds were responsible for the antibacterial activity of the strain. In this
      article, we discuss with the mutation of the marine Streptomyces sp. AH2,
      bioactivity evaluation, fermentation and isolation of the microbial metabolites.
      Moreover, we study to first time in detail the 1D and 2D NMR and ESI MS data
      including ESI MS(2) and MS(3) patterns combined with HRESI MS of erythromycin A.

PMID- 20046739
TI  - Spinacia oleracea Modulates Radiation-Induced Biochemical Changes in Mice Testis.
AB  - The present study is an attempt to investigate the radioprotective efficacy of
      spinach against radiation induced oxidative stress, since its leaves are rich in
      antioxidants like carotenoids (beta-carotene, lutein and zeaxanthin) and high
      content of proteins, minerals, vitamin C. For the experimental study, healthy
      Swiss mice were selected from an inbred colony and divided into four groups.
      Group I (normal) it did not receive any treatment. Group II (drug treated) was
      orally supplemented with extract of spinach extract once daily at the dose of
      1100 mg/kg for fifteen consecutive days. Group III (control) received distilled
      water orally equivalent to spinach extract for fifteen days than exposed to 5 Gy
      of gamma radiation. Group IV (experimental) was also administered orally with
      spinach extract for 15 consecutive days once daily. Thereafter, exposed to single
      dose of 5Gy of gamma radiation. After the exposure mice were than sacrificed at
      different autopsy intervals viz. 1, 3, 7, 15 and 30 days. Testis was removed for
      various biochemical estimations viz. LPO, protein, cholesterol and glycogen.
      Radiation induced augmentation in lipid peroxidation, glycogen and cholesterol
      values were significantly ameliorated by supplementation of SE extract, whereas
      radiation induced deficit in protein content could be elevated. This indicates
      that spinach extract pre - treatment renders protection against various
      biochemical changes in the mice testis to some extent if taken continuously which
      might be due to synergistic effect of antioxidant constituents present in the
      spinach.

PMID- 20046740
TI  - Attenuation of Acute and Chronic Restraint Stress-induced Perturbations in
      Experimental Animals by Nelumbo nucifera Gaertn.
AB  - Aqueous extract of leaves of Nelumbo nucifera was investigated on acute stress
      (immobilization stress)-induced biochemical alterations in Swiss mice. The
      animals were also subjected to acute physical stress (swimming endurance test)
      and acute chemical stress (writhing test) to gauge the antistress potential of
      the extract. Further to evaluate the antistress activity of Nelumbo nucifera in
      chronic stress condition, fresh Wistar rats were subjected to cold restraint
      stress (4 degrees for 1 h) for 7 days after 21 days of pretreatment with the
      extract. Stimulation of hypothalamus pituitary adrenal axis in stressful
      condition alters plasma glucose, triglyceride, cholesterol, total protein and
      corticosterone levels. Pretreatment with the extract significantly ameliorated
      the stress-induced variations in these biochemical levels in both acute and
      chronic stress models. The extract treated animals showed increase in swimming
      endurance time and reduced number of writhes in physical and chemical-induced
      stress models respectively. Treatment groups also reverted back perturbed
      neurotransmitter levels (norepinephrine, dopamine and 5-hydroxytryptamine) in
      brain as well as increase in adrenal gland weights and atrophy of spleen caused
      by cold chronic stress. In mice immunized with sheep red blood cells, treatment
      groups subjected to restraint stress prevented the humoral immune response to the
      antigen. Histopathological studies of adrenal gland of stress control group
      revealed vacuolar degeneration, loss of architecture and formation of lesions in
      the cortex, which was reversed by extract treatment. The results indicate that
      aqueous extract of Nelumbo nucifera has significant adaptogenic activity against
      a variety of biochemical, histological, physiological and immunological
      perturbations in acute and chronic stress models.

PMID- 20046741
TI  - Formulation, and Evaluation of Pentoxifylline-Loaded Poly(epsilon-caprolactone)
      Microspheres.
AB  - Pentoxifylline-loaded poly(epsilon-caprolactone) microspheres were prepared by
      solvent evaporation technique with different drug to carrier ratio F1 (1:3), F2
      (1:4), F3 (1:5) and F4 (1:6). The microspheres were characterized for particle
      size, scanning electron microscopy, FT-IR study, percentage yield, drug
      entrapment, stability studies and for in vitro release kinetics. The shape of
      microspheres was found to be spherical by SEM. The size of microspheres was found
      to be ranging 59.3+/-6.3mum to 86.22+/-4.23 mum. Among the four drug to carrier
      ratio, F3 (1:5) showed maximum percentage yield of 83.34+/-2.46% and F2 (1:4)
      showed highest drug entrapment of 76.92+/-3.24% w/w. It was found that there was
      no interaction between drug and polymer by FT-IR study. No appreciable difference
      was observed in the extent of degradation of product during 60 d in the
      microspheres, which were stored at various temperatures. In the in vitro release
      study formulation F2 (1:4) showed 90.34% drug release at 15 h and found to be
      sustained. The release followed Higuchi kinetics indicating diffusion controlled
      drug release.

PMID- 20046742
TI  - Design and development of mixed film of pectin: ethyl cellulose for colon
      specific drug delivery of sennosides and triphala.
AB  - The present study was aimed at developing colon specific drug delivery system for
      sennosides and Triphala. These drugs are reputed Ayurvedic medicines for
      constipation in India. The proposed device explored the application of pectin and
      ethyl cellulose as a mixed film for colon specific delivery. This mixed film was
      prepared using non-aqueous solvents like acetone and isopropyl alcohol. A 32
      factorial design was adopted to optimize the formulation variables like, ratio of
      ethyl cellulose to pectin (X1) and coat weight (X2). The rate and extent of drug
      release were found to be related to the thickness and the ratio of pectin to
      ethyl cellulose within the film. Statistical treatments to the drug release data
      revealed that the X1 variable was more important than X2. Under simulated colonic
      conditions, drug release was more pronounced from coating formulations containing
      higher proportions of pectin. The surface of the device was coated with Eudragit
      S100 to ensure that the device was more pH dependent and trigger the drug release
      only at higher pH. The final product is expected to have the advantage of being
      biodegradable and pH dependant. This type of a film effectively releases the drug
      while maintaining its integrity.

PMID- 20046743
TI  - Novel atomic absorption spectrometric and rapid spectrophotometric methods for
      the quantitation of paracetamol in saliva: application to pharmacokinetic
      studies.
AB  - A novel atomic absorption spectrometric method and two highly sensitive
      spectrophotometric methods were developed for the determination of paracetamol.
      These techniques based on the oxidation of paracetamol by iron (III) (method I);
      oxidation of p-aminophenol after the hydrolysis of paracetamol (method II). Iron
      (II) then reacts with potassium ferricyanide to form Prussian blue color with a
      maximum absorbance at 700 nm. The atomic absorption method was accomplished by
      extracting the excess iron (III) in method II and aspirates the aqueous layer
      into air-acetylene flame to measure the absorbance of iron (II) at 302.1 nm. The
      reactions have been spectrometrically evaluated to attain optimum experimental
      conditions. Linear responses were exhibited over the ranges 1.0-10, 0.2-2.0 and
      0.1-1.0 mug/ml for method I, method II and atomic absorption spectrometric
      method, respectively. A high sensitivity is recorded for the proposed methods I
      and II and atomic absorption spectrometric method value indicate: 0.05, 0.022 and
      0.012 mug/ml, respectively. The limit of quantitation of paracetamol by method II
      and atomic absorption spectrometric method were 0.20 and 0.10 mug/ml. Method II
      and the atomic absorption spectrometric method were applied to demonstrate a
      pharmacokinetic study by means of salivary samples in normal volunteers who
      received 1.0 g paracetamol. Intra and inter-day precision did not exceed 6.9%.

PMID- 20046744
TI  - Chronomodulated drug delivery system of salbutamol sulphate for the treatment of
      nocturnal asthma.
AB  - A time dependent pulsed release system consisting of an effervescent core
      surrounded by consecutive layers of swelling and rupturable polymers was prepared
      and evaluated. The cores containing salbutamol sulphate as bioactive agent were
      prepared by direct compression method using different ratios of microcrystalline
      cellulose and effervescent agent and then coated sequentially with an inner
      swelling layer containing a hydrocolloid, hydroxypropylmethylcellulose E5 and an
      outer rupturable layer having Eudragit RL/RS (1:1). The effects of various
      processing and formulative parameters on the performance of system were studied.
      The rupture and dissolution tests were studied using the USP paddle method at 50
      rpm in 0.1 N HCl and phosphate buffer pH 6.8. The lag time of the drug release
      decreased by increasing the inner swelling layer and increased by increasing the
      rupturing layer level. All the results obtained in the present study suggest that
      osmotic pumping effect was involved which eventually lead to the drug release.

PMID- 20046745
TI  - HPLC Method for Determination of Enantiomeric Purity of a Novel Respiratory
      Fluoroquinolone: WCK 1152.
AB  - A sensitive, simple, specific, precise, accurate and rugged method for
      determination of enantiomeric purity of S-(-)-1-cyclopropyl-6-fluoro-1,4-dihydro
      8-methoxy-7-{4-amino-3,3-dimethylpiperidin-1-yl}-4-oxo-quinoline-3-carboxylic
      acid hydrochloride monohydrate, WCK 1152, a new drug substance has been
      developed. The method is based on prederivatization of analyte to diastereomer
      followed by RP-HPLC using endcapped C-18 stationary phase. Column was maintained
      at 30 degrees C. The UV/Vis detector was operated at 290 nm. Flow rate of the
      mobile phase was 1.25 ml/min. The method offers excellent separation of two
      enantiomers with resolution more than 4 and tailing factor less than 1.5. The
      method was validated for the quantification of R-(+)-enantiomer impurity, WCK
      1153 in the bulk drug. Calibration curves showed excellent linearity over the
      concentration range of 0.1 to 1.5 mg/ml for WCK 1152 and 0.01 to 0.15 mg/ml for
      WCK 1153. Precision of the method was 1.13%. Limit of detection and limit of
      quantitation of the method for WCK 1152 were 0.0006 mg/ml and 0.0018 mg/ml and
      for WCK 1153 were 0.0007 mg/ml and 0.0021 mg/ml, respectively. Average recovery
      of the WCK 1153 in WCK 1152 was 94.4%. This method was employed in determining
      enantiomeric purity of clinical trial batches of WCK 1152.

PMID- 20046746
TI  - Evaluation of Antioxidant Potential of Kaempferia rotunda Linn.
AB  - The plant Kaempferia rotunda Linn. has been explored for its anti oxidant
      potential in the present study. The antioxidant property was assessed by lipid
      peroxidation markers such as malonaldehyde (MDA) and 4-hydroxyl-2-nonenal (4
      HNE). The lipid peroxidation byproducts are highly toxic and responsible for
      various diseases like myocardial infarction, diabetes mellitus, hepatic injury,
      atherosclerosis, rheumatoid arthritis and cancer. The chemical constituents of
      the plant were critically and qualitatively analyzed to confirm the presence of
      flavonoids and phenolic derivatives. Hence our objective has been designed to
      evaluate the antioxidant effect of Kaempferia rotunda linn. and its contribution
      to control the lipid peroxidation.

PMID- 20046747
TI  - Hepatoprotective Activity of Ficus carica Leaf Extract on Rifampicin-Induced
      Hepatic Damage in Rats.
AB  - Shade dried leaves of Ficus carica were extracted using petroleum ether (60-80
      degrees ) and tested for antihepatotoxic activity on rats treated with 50 mg/kg
      of rifampicin orally. The parameters assessed were serum levels of glutamic
      oxaloacetate transaminase, glutamic pyruvic transaminase, bilirubin and
      histological changes in liver. Liver weights and pentobarbitione sleeping time as
      a functional parameter were also monitored. There was significant reversal of
      biochemical, histological and functional changes induced by rifampicin treatment
      in rats by petroleum ether extract treatment, indicating promising
      hepatoprotective activity.

PMID- 20046748
TI  - Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From
      Their Combined Dosage Form.
AB  - A simple, precise, sensitive, rapid and reproducible HPTLC method for the
      simultaneous estimation of the rabeprazole and itopride hydrochloride in tablets
      was developed and validated. This method involves separation of the components by
      TLC on precoated silica gel G60F254 plate with solvent system of n-butanol,
      toluene and ammonia (8.5:0.5:1 v/v/v) and detection was carried out
      densitometrically using a UV detector at 288 nm in absorbance mode. This system
      was found to give compact spots for rabeprazole (Rf value of 0.23 0.02) and for
      itopride hydrochloride (Rf value of 0.75+/-0.02). Linearity was found to be in
      the range of 40-200 ng/spot and 300-1500 ng/spot for rabeprazole and itopride
      hydrochloride. The limit of detection and limit of quantification for rabeprazole
      were 10 and 20 ng/spot and for itopride hydrochloride were 50 and 100 ng/spot,
      respectively. The method was found to be beneficial for the routine analysis of
      combined dosage form.

PMID- 20046749
TI  - Evaluation of antispasmodic activity of different Shodhit guggul using different
      shodhan process.
AB  - According to ayurvedic texts shodhan vidhi is an important process which enhances
      the biological activity of a compound and reduces the toxicity at the same time.
      Before incorporating into formulations, guggul is processed using Shodhan vidhi
      involving different shodhan dravyas like gulvel, gomutra, triphala, dashmul. We
      have evaluated the antispasmodic activity of guggul on ileum of guinea pig and
      Wistar rats. The animals were sacrificed and ileum tissue of guinea pig and rat
      was isolated and tested for antispasmodic activity using different spasmogens
      like acetylcholine, histamine and barium chloride. It was observed that the
      different shodhit guggul (shudha guggul) i.e. processed using different shodhan
      vidhi, showed good antispasmodic activity as compared to Ashudha guggul. When
      acetylcholine was used as spasmogen, gulvel and triphala shodhit guggul showed
      good antispasmodic activity than other shodhit guggul. Thus shodhan vidhi
      enhances the therapeutic properties of guggul.

PMID- 20046750
TI  - Simultaneous Determination of Valsartan and Hydrochlorothiazide in Tablets by RP
      HPLC.
AB  - A simple, reproducible and efficient reverse phase high performance liquid
      chromatographic method was developed for simultaneous determination of valsartan
      and hydrochlorothiazide in tablets. A column having 200 x 4.6 mm i.d. in
      isocratic mode with mobile phase containing
      methanol:acetonitrile:water:isopropylalcohol (22:18:68:2; adjusted to pH 8.0
      using triethylamine; v/v) was used. The flow rate was 1.0 ml/min and effluent was
      monitored at 270 nm. The retention time (min) and linearity range (mug/ml) for
      valsartan and hydrochlorothiazide were (3.42, 8.43) and (5-150, 78-234),
      respectively. The developed method was found to be accurate, precise and
      selective for simultaneous determination of valsartan and hydrochlorothiazide in
      tablets.

PMID- 20046751
TI  - Diabetic nephropathy: prescription trends in tertiary care.
AB  - Diabetic nephropathy is a leading cause of end stage renal disease. Drug
      utilization studies could promote rational drug use. The objective of this study
      was to evaluate prescribing trends in hospitalized patients with diabetic
      nephropathy. A prospective, observational study was conducted in a tertiary care
      hospital. The demographic, disease and treatment data of patients with diabetic
      nephropathy were collected for a period of six months and analysed. Drugs were
      classified using World Health Organization recommended Anatomic Therapeutic
      Chemical classification. A total of 755 drugs (7.4 drugs per prescription) were
      prescribed to 102 study patients, who were all hypertensive and in late stages of
      diabetic nephropathy. Drug classes with largest representation were those acting
      on gastrointestinal tract plus metabolism (37%) and cardiovascular drugs (28%).
      Calcium channel blockers represented the largest antihypertensive drug class
      (41%). Almost three-fourths of patients received more than one antihypertensive
      agent. Approximately 37% of patients did not receive any antidiabetic medication.
      Of those who did, prescriptions for insulin (91%) exceeded those of oral
      hypoglycaemic drugs (9%). Antimicrobials accounted for 10.2% of all drugs
      prescribed, of which 31.8% were quinolones. Drugs prescribed by generic name
      accounted for 11.98%. While all patients received antihypertensive therapy, more
      than a third were not on any antidiabetic treatment. Antihypertensive poly
      therapy was observed in the majority with calcium channel blockers being most
      frequently prescribed antihypertensive drug class. Insulin was the preferred to
      hypoglycaemic drugs.

PMID- 20046752
TI  - Antidiabetic Activity of the Ethanol Extract of Capparis sepiaria L Leaves.
AB  - Capparis sepiaria L, a profusely branched hedge plant, is used in Indian
      traditional medicine. Capparis sepiaria leaves were extracted with ethanol and
      concentrated to dryness. The LD(50) value was determined as 894.43 mg/kg body
      weight by acute toxicity study. The ethanol extract was investigated for possible
      hypoglycemic effect produced by single oral administration at various dose levels
      100, 200 and 300 mg/kg in the streptozotocin induced diabetic rats and compared
      against normal saline control and the standard glibenclamide. A maximum fall of
      plasma glucose level 9.40%; 13.57%; 15.25% and 18.80% was observed after 12 h of
      treatment when administered with ethanol extract of Capparis sepiaria at 100, 200
      and 300 mg/kg, and glibenclamide 10 mg/kg dose, respectively. The findings from
      the study suggest that the Capparis sepiaria leaves may be prescribed as an
      adjunct to traditional formulation and drug treatment for controlling diabetes
      mellitus.

PMID- 20046753
TI  - Synthesis and Antiulcer Activity Studies of 2-(1'-Iminothioimido Substituted)-1'
      Substituted Phenylbenzoic acids.
AB  - Certain 2-(1'-iminothioimido substituted)-1'-substituted phenybenzoic acids (P(1
      9)) were synthesized by reaction of phthalic anhydride with benzotriazole, 2
      mercapto benzothiazole and 2-p-amino phenyl benzimidazole, respectively (A(1-3))
      followed by imine formation with Schiff bases of thiourea with salicylaldehyde,
      furfuraldehyde and 1-phenyl-3-methyl-5-pyrazolone. Antiulcer activity was
      evaluated using reduction in total acidity, free acidity and ulcer index as
      parameters. Compounds P(3), P(6), P(7) and P(9)(100 mg/kg) showed significant (P<
      0.001) antiulcer action compared to control and omeprazole (40 mg/kg).

PMID- 20046754
TI  - Simultaneous Estimation of Metformin Hydrochloride and Pioglitazone Hydrochloride
      by RPHPLC Method from Combined Tablet Dosage Form.
AB  - A high performance reverse phase liquid chromatographic procedure is developed
      for simultaneous estimation of metformin hydrochloride and pioglitazone
      hydrochloride in combined tablet dosage form. The mobile phase used was a
      combination of acetonitrile:water:acetic acid (60:40:0.3) and the pH was adjusted
      to 5.5 by adding triethylamine. The detection of the combined dosage form was
      carried out at 230 nm and a flow rate employed was 1 ml/min. Linearity was
      obtained in the concentration range of 0.015 to 0.120 mug/ml of pioglitazone
      hydrochloride and 0.5 to 4.0 mug/ml of metformin hydrochloride with a correlation
      coefficient of 0.9992 and 0.9975. The results of the analysis were validated
      statistically and recovery studies confirmed the accuracy and precision of the
      proposed method.

PMID- 20046755
TI  - A Validated HPTLC Method for Determination of Ondansetron in Combination with
      Omeprazole or Rabeprazole in Solid Dosage Form.
AB  - A simple, precise, accurate and rapid high performance thin layer chromatographic
      method has been developed for the simultaneous estimation of ondansetron
      combinations in solid dosage form with omeprazole and rabeprazole, respectively.
      The method involved separation of components by TLC on a precoated silica gel 60
      F(254) using a mixture of dichloromethane:methanol (9:1) as a mobile phase.
      Detection of spots was carried out at 309 nm and 294 nm for ondansetron with
      omeprazole and ondansetron with rabeprazole combinations, respectively. The mean
      retardation factor for ondansetron and omeprazole were found to be 0.42+/-0.02,
      0.54+/-0.03, respectively while for ondansetron and rabeprazole, 0.41+/- 0.02 and
      0.51+/-0.02, respectively. The linearity and range was 0.1 to 0.5 mug/spot for
      three drugs. The method was validated for precision, accuracy and
      reproducibility.

PMID- 20046756
TI  - Antimicrobial Activity of Terminalia catappa, Manilkara zapota and Piper betel
      Leaf Extract.
AB  - Aqueous and methanol extract of the leaves of Terminalia catappa L., Manilkara
      zapota L. and Piper betel L. were evaluated for antibacterial activity against 10
      Gram positive, 12 Gram negative bacteria and one fungal strain, Candida
      tropicalis. Piperacillin and gentamicin were used as standards for antibacterial
      assay, while fluconazole was used as standard for antifungal assay. The three
      plants showed different degree of activity against the microorganisms
      investigated. The methanolic extract was considerably more effective than aqueous
      extract in inhibiting the investigated microbial strains. The most active
      antimicrobial plant was Piper betel.

PMID- 20046757
TI  - Simultaneous spectrophotometric estimation of paracetamol and metoclopramide
      hydrochloride in solid dosage form.
AB  - Two simple, accurate, rapid and economical spectrophotometric methods have been
      developed for the simultaneous determination of paracetamol and metoclopramide
      hydrochloride from tablet dosage form. The first method developed employs
      formation and solving simultaneous equations using 248.6 nm and 275.6 nm as two
      wavelengths for formation of equations. Second method is absorbance ratio in
      which wavelengths selected were 265.6 nm as isoabsorptive point and 275.6 nm as
      lambdamax of paracetamol. Both the drugs and their mixtures obey Beer-Lamberts
      law at selected wavelengths at given concentration range. The methods have been
      validated statistically and by recovery studies. The results of analysis have
      been validated statistically and by recovery studies.

PMID- 20046758
TI  - Quantitative analysis of propranolol hydrochloride by high performance thin layer
      chromatography.
AB  - A simple, accurate and precise HPTLC method has been developed for estimation of
      propranolol hydrochloride from bulk drug and tablet formulations. The separation
      was achieved on TLC plates using appropriate solvent system. The spots so
      developed were densitometrically scanned at 290 nm. The linearity of the method
      was found to be within the concentration range of 200-2000 ng/spot. The
      validation parameters, tested in accordance with the requirements of ICH
      guidelines, prove the suitability of this method. The method was successively
      applied for determination of drug in tablets, wherein, no interference from
      tablet excipients was observed.

PMID- 20046759
TI  - High performance thin layer chromatographic method for simultaneous estimation of
      Ibuprofen and pseudoephedrine hydrochloride.
AB  - High performance thin layer chromatographic method is developed for simultaneous
      estimation of ibuprofen and pseudoephedrine hydrochloride in tablets. Silica gel
      60F(254) plates were used as stationary phase and t.butanol: ethyl acetate:
      glacial acetic acid: water (7:4:2:2 v/v) as mobile phase. Wavelength selected for
      analysis was 254 nm. Percent estimation of ibuprofen and pseudoephedrine
      hydrochloride was found to be 99.56% and 98.77%, respectively. Percent recovery
      for both the drugs was found in the range of 98.27% to 100.91%, respectively.

PMID- 20046760
TI  - Reverse phase high performance liquid chromatographic method for the analysis of
      letrozole in pharmaceutical dosage forms.
AB  - A rapid and sensitive reverse phase high performance liquid chromatographic
      method is depicted for the qualitative and quantitative assay of letrozole in
      pharmaceutical dosage forms. Letrozole was chromatographed on a reverse phase C18
      column with a mobile phase consisting of acetonitrile and phosphate buffer (pH
      7.8) in the ratio of 70:30 v/v. The mobile phase was pumped at a flow rate of 1
      ml/min. Acenaphthene was used as an internal standard and the eluents were
      monitored at 232 nm. The retention time of the drug was 3.385 min. With this
      method, linearity was observed in the range of 10-100 mug/ml. The LOD and LOQ
      were found to be 0.51 mug/ml and 1.52 mug/ml, respectively. The method was found
      to be applicable for analysis of drug in tablets. The results of the analysis
      were validated statistically.

PMID- 20046761
TI  - Antimicrobial studies on extracts of four species of stachys.
AB  - The antimicrobial activity of the methanol extracts of the dried flowering aerial
      parts of Stachys byzantina, S. inflata, S. lavandulifolia and S. laxa (Labiatae)
      were studied using the disc diffusion method and determination of minimum
      inhibitory concentration (MIC) values against Staphylococcus aureus,
      Streptococcus sanguis, Escherichia coli, Pseudomonas aeroginosa, Klebsiella
      pneumoniae, Aspergilus niger and Candida albicans. The extracts of plants
      exhibited concentration-dependent antibacterial activity against the bacteria
      tested. The extracts were more active against Gram-positive microorganisms. The
      extracts, however, did not show any antifungal activity.

PMID- 20046762
TI  - Determination of ebastine in pharmaceutical formulations by HPLC.
AB  - A simple, precise and rapid RP-HPLC method was developed for the determination of
      ebastine in pharmaceutical formulations. The method was carried out on a
      Phenomenex RP-C18 column using a mixture of methanol and water (90:10) and
      detection was done at 262 nm. The linearity range was 5-100 mug/ml. The intra-day
      and inter-day precision were in the range of 0.22% to 0.49% and 0.24% to 0.73%,
      respectively.

PMID- 20046763
TI  - Formulation optimization of propranolol hydrochloride microcapsules employing
      central composite design.
AB  - A central composite design was employed to produce microcapsules of propranolol
      hydrochloride by o/o emulsion solvent evaporation technique using a mixture of
      cellulose acetate butyrate as coat material and span-80 as an emulsifier. The
      effect of formulation variables namely levels of cellulose acetate butyrate
      (X(1)) and percentage of Span-80 (X(2)) on encapsulation efficiency (Y(1)), drug
      release at the end of 1.5 h (Y(2)), 4 h (Y(3)), 8 h (Y(4)), 14 h (Y(5)), and 24 h
      (Y(6)) were evaluated using the F test. Mathematical models containing only the
      significant terms were generated for each response parameter using multiple
      linear regression analysis and analysis of variance. Both the formulation
      variables exerted a significant influence (P <0.05) on Y(1) whereas the cellulose
      acetate butyrate level emerged as the lone factor which significantly influenced
      the other response parameters. Numerical optimization using desirability approach
      was employed to develop an optimized formulation by setting constraints on the
      dependent and independent variables. The experimental values of Y(1), Y(2), Y(3),
      Y(4), Y(5), and Y(6) for the optimized formulation was found to be 92.86+/-1.56%
      w/w, 29.58+/-1.22%, 48.56+/-2.56%, 60.85+/-2.35%, 76.23+/-3.16% and 95.12+/
      2.41%, respectively which were in close agreement with those predicted by the
      mathematical models. The drug release from microcapsules followed first order
      kinetics and was characterized by Higuchi diffusion model. The optimized
      microcapsule formulation developed was found to comply with the USP drug release
      test-1 for extended release propranolol hydrochloride capsules.

PMID- 20046764
TI  - Herbal excipients in novel drug delivery systems.
AB  - The use of natural excipients to deliver the bioactive agents has been hampered
      by the synthetic materials. However advantages offered by these natural
      excipients are their being non-toxic, less expensive and freely available. The
      performance of the excipients partly determines the quality of the medicines. The
      traditional concept of the excipients as any component other than the active
      substance has undergone a substantial evolution from an inert and cheap vehicle
      to an essential constituent of the formulation. Excipients are any component
      other than the active substance(s) intentionally added to formulation of a dosage
      form. This article gives an overview of herbal excipients which are used in
      conventional dosage forms as well as novel drug delivery systems.

PMID- 20046766
TI  - Dendrimeric nanoarchitectures mediated transdermal and oral delivery of
      bioactives.
AB  - Transdermal route is an evolving panorama in novel drug deliverance and with oral
      route they proffer immense potential. Most recently there is hastening in
      approaches for delivering bioactives via these routes, amongst them revolution
      has been made by dendrimers. Encapsulation and conjugation of bioactives with
      these virus sized robots have shown immense employment for delivery of
      hydrophobic and labile remedies. Transport of these nano-cruises from corner to
      corner of skin and through epithelial hurdle of gastrointestinal tract depends
      upon dendrimer characteristics. An improved thoughtful of these characteristics
      is an obligation for their use in these rambling fields. These characteristics
      embrace generation size, molecular weight, surface charge, incubation time and
      concentration. This context demarcates the imperative role of dendrimers in
      transdermal and oral drug delivery. This review also highlights concerning
      mechanism of convey of nanoarrays via epithelial hurdle of GIT.

PMID- 20046765
TI  - Antifungals: need to search for a new molecular target.
AB  - In the 1990s, drug resistance has become an important problem in a variety of
      infectious diseases including human immunodeficiency virus infection,
      tuberculosis, and other bacterial infections which have profound effects on human
      health. At the same time, there have been dramatic increase in the incidence of
      fungal infections, which are probably the result of alterations in immune status
      associated with the acquired immuno deficiency syndrome epidemic, cancer
      chemotherapy, and organ and bone marrow transplantation. The rise in the
      incidence of fungal infections has exacerbated the need for the next generation
      of antifungal agents, since many of the currently available drugs have
      undesirable side effects, are ineffective against new or reemerging fungi, or
      lead to the rapid development of the resistance. This review will focus on the
      pathogenic yeast Candida albicans, since a large body of work on the factors and
      mechanism associated with antifungal drug resistance in this organism is reported
      sufficiently. It will certainly elaborate the probable molecular targets for drug
      design, discovered to date.

PMID- 20046767
TI  - Evaluation of Antiasthmatic Activity of Curculigo orchioides Gaertn. Rhizomes.
AB  - The ethanol extract of Curculigo orchioides was evaluated for antiasthmatic
      activity by using various in vitro and in vivo animal models. In vitro models
      like isolated goat tracheal chain preparation and isolated guinea pig ileum
      preparation were studied to know basic mechanism by which extract shows relaxant
      activity. The study showed that extract is effective against histamine-induced
      contraction. In isolated goat tracheal chain preparation and isolated guinea pig
      ileum preparation extract exhibits maximum relaxant effect (p< 0.01) against
      histamine at concentrations 100mug/ml and 25mug/ml respectively. Animal studies
      involved use of histamine induced bronchoconstriction in guinea pigs, egg albumin
      induced passive paw anaphylaxis in rats and haloperidol-induced catalepsy in
      mice. These studies showed significant (p< 0.01) protection at lower doses while
      further increase in the dose level showed reduced activity. Biochemical
      estimations in milk-induced total leukocytes count and milk-induced differential
      leukocyte count were also studied. In this study there was maximum increase in
      leucocytes and lymphocytes (99%) and maximum decrease in eosinophils up to 0% at
      dose 375mg/kg p.o. body weight was observed. The results of these studies
      indicated usefulness of ethanol extract of Curculigo orchioides in asthma.

PMID- 20046769
TI  - Chemometric simultaneous estimation of clopidogrel bisulphate and aspirin from
      combined dosage form.
AB  - Two chemometric methods, inverse least square and classical least square, were
      applied to simultaneous assay of clopidogrel bisulphate and aspirin in their
      combined dosage tablet formulation. Twelve mixed solutions were prepared for the
      chemometric calibration as training set and 10 mixed solutions were prepared as
      validation set. The absorbance data matrix was obtained by measuring the
      absorbance at 16 wavelength points, from 220 to 250 nm with the interval of 2 nm
      (Deltalambda= 2 nm). The developed calibrations were successfully tested for
      laboratory mixtures as well as commercial tablet formulation for their
      clopidogrel bisulphate and aspirin concentration. Mean recoveries for clopidogrel
      bisulphate and aspirin were found to be in good agreement with the label claim.

PMID- 20046768
TI  - A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG
      (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin.
AB  - Curcumin, the bioactive component of turmeric, Curcuma longa has an exceptionally
      wide spectrum of activities including antioxidant, anti-inflammatory and anti
      cancer properties, and is currently under different phases of clinical trials for
      various types of soft tissue cancers. However, although in vitro and animal
      studies have shown anticancer activities of curcumin for virtually all types of
      human cancers, its poor bioavailability in the human body has severely limited
      its application to these diseases. Methods to increase its oral bioavailability
      are a subject of intense current research. Reconstituting curcumin with the non
      curcuminoid components of turmeric has been found to increase the bioavailability
      substantially. In the present clinical study to determine the bioavailability of
      curcuminoids, a patented formulation, BCM-95((R))CG was tested on human volunteer
      group. Normal curcumin was used in the control group. Curcumin content in blood
      was estimated at periodical intervals. After a washout period of two weeks the
      control group and drug group were crossed over BCM-95((R))CG and curcumin,
      respectively. It was also compared with a combination of curcumin-lecithin
      piperine which was earlier shown to provide enhanced bioavailability. The results
      of the study indicate that the relative bioavailability of BCM-95((R))CG
      (Biocurcumax) was about 6.93-fold compared to normal curcumin and about 6.3-fold
      compared to curcumin-lecithin-piperine formula. BCM-95((R))CG thus, has potential
      for widespread application for various chronic diseases.

PMID- 20046770
TI  - Preparation and evaluation of transdermal drug delivery system of etoricoxib
      using modified chitosan.
AB  - In the present investigation chitosan has been chemically modified by treating
      with two different aldehydes like acetaldehyde and propionaldehyde to form
      Schiff's bases. Schiff's bases of chitosan with acetaldehyde and propionaldehyde
      were named as polymer A and polymer B, respectively. Fourier Transform Infra Red
      (FTIR) spectral data have confirmed the reaction carried out on chitosan. Drug
      free polymeric films of chitosan, chemically modified chitosan and
      chitosan/hydroxypropylmethylcellulose blend were prepared and evaluated for
      various physicochemical characters. Further, the films were incorporated with
      anti-inflammatory drug, etoricoxib using glycerol as plasticizer. The drug loaded
      films were cross-linked with sodium citrate and studied for permeation
      characteristics across dialysis membrane and rat skin. All the films were
      evaluated for bursting strength, swelling index, moisture uptake, thickness
      uniformity, drug content uniformity, tensile strength, percent elongation at
      break, percent flatness, water vapour transmission rate and in vitro drug
      permeation study.

PMID- 20046771
TI  - In vitro Evaluation of the Effect of Combination of Hydrophilic and Hydrophobic
      Polymers on Controlled Release Zidovudine Matrix Tablets.
AB  - The aim of the present study was to prepare and characterize controlled-release
      matrix tablets of zidovudine using hydrophilic HPMC K4 M or Carbopol 934 alone or
      in combination with hydrophobic ethyl cellulose. Release kinetics was evaluated
      by using USP XXIV dissolution apparatus No.2 (paddle) type. Scanning electron
      microscopy was used to visualize the effect of dissolution medium on matrix
      tablet surface. The in vitro results of controlled - release zidovudine tablets
      were compared with conventional marketed tablet Zidovir. The in vitro drug
      release study revealed that HPMC K4 M or Carbopol 934 preparation was able to
      sustain the drug release near to 6 hours. Combining HPMC K4 M or Carbopol 934
      with ethyl cellulose sustained the drug release for nearly 12 h. The in vitro
      evaluation showed that the drug release may be by diffusion along with erosion.
      Results suggest that the developed controlled-release tablets of zidovudine could
      perform therapeutically better than marketed dosage forms, leading to improve
      efficacy, controlling the release and better patient compliance.

PMID- 20046772
TI  - A Study on Improvement of Solubility of Rofecoxib and its effect on Permeation of
      Drug from Topical Formulations.
AB  - Rofecoxib, a practically insoluble cox-2 selective nonsteroidal antiinflammatory
      agent was subjected to improvement in solubility by preparing its binary mixtures
      with beta cyclodextrin using various methods such as physical mixing, co
      grinding, kneading with aqueous methanol and co-evaporation from methanol-water
      mixture. Characterization of the resulting binary mixtures by differential
      scanning calorimetry and X-ray diffraction studies indicated partial
      amorphization of the drug in its binary mixtures. In vitro dissolution studies
      exhibited remarkable increase in rate and extent of dissolution of the drug from
      its complexes with beta -cyclodextrin. Pure rofecoxib as well as its co-ground
      binary mixture were formulated as aqueous gels for topical application. In vitro
      skin permeation of rofecoxib from formulation containing rofecoxib-cyclodextrin
      complex was significantly higher (p<0.05) at 1, 2, 12, 18 and 24 hr as compared
      to formulation containing pure rofecoxib. This could be attributed to better
      solubility of binary mixture in the aqueous gel vehicle leading to greater
      concentration gradient between the vehicle and skin and hence higher flux of the
      drug.

PMID- 20046773
TI  - Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.
AB  - The purpose of this research was to prepare a sustained release drug delivery
      system of venlafaxine hydrochloride by using a wax matrix system. The effects of
      bees wax and carnauba wax on drug release profile was investigated. A 3(2) full
      factorial design was applied to systemically optimize the drug release profile.
      Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent
      variables and release after 12 h and time required for 50% (t(50)) drug release
      were selected as dependent variables. A mathematical model was generated for each
      response parameter. Both waxes retarded release after 12 h and increases the
      t(50) but bees wax showed significant influence. The drug release pattern for all
      the formulation combinations was found to be approaching Peppas kinetic model.
      Suitable combination of two waxes provided fairly good regulated release profile.
      The response surfaces and contour plots for each response parameter are presented
      for further interpretation of the results. The optimum formulations were chosen
      and their predicted results found to be in close agreement with experimental
      findings.

PMID- 20046774
TI  - Development and in vitro Evaluation of Enteric Coated Multiparticulate System for
      Resistant Tuberculosis.
AB  - The multiparticulate formulation of sodium para aminosalicylate for oral
      administration was developed by extrusion spheronization technique.
      Microcrystalline cellulose was used as filler in concentration of 14.4% w/w.
      Pellets were coated with Eudragit L 30 D-55 using fluidized bed processor.
      Different weight gains of acrylic polymer were applied onto the pellets and
      evaluated for in vitro dissolution behavior in 0.1 N HCl for two hours and then
      media was changed to phosphate buffer pH 6.8. A 60% w/w coating level of Eudragit
      L30 D 55 has produced the most acceptable results against the gastric attack. 3%
      Seal coat of HPMC E5 was also applied in order to protect the drug from migration
      into the Eudragit coat and film coat was applied in order to prevent aggregation
      of pellets in the dissolution media. Morphological characteristics of developed
      pellets were also investigated by scanning electron microscopy and found to be
      smooth and spherical. Developed system was found to be suitable for the delivery
      of Sod PAS in to intestinal region.

PMID- 20046775
TI  - Characterization of hydrochloride and tannate salts of diphenhydramine.
AB  - Proper characterization is an important aspect of any dosage form design. The
      objective of this work was to characterize tannate salt and hydrochloride salt of
      diphenhydramine. As a part of characterization studies, Differential scanning
      calorimetry was used to investigate thermal effects and nature of salts,
      supported by X-ray powder diffraction. Scanning electron microphotographs was
      used to surface topography of salts of diphenhydramine. Fourier-transform
      infrared spectroscopy, solubility study and flowability studies were carried out
      as part of characterization. Differential scanning calorimetry and X-ray powder
      diffraction studies indicated amorphous nature of the tannate while hydrochloride
      salt has crystalline properties. Scanning electron microphotographs indicated the
      differences in surface topography between both the salts. Solubility studies at
      different pH showed pH dependant solubility of both the salts and less solubility
      of tannate. Stability of bulk drug at accelerated conditions of 40( degrees )/75%
      RH was determined for both salts. Good stability of both salts was observed.

PMID- 20046776
TI  - Immune Augmentation of Single Contact Hepatitis B Vaccine by Using PLGA
      Microspheres as an Adjuvant.
AB  - The present study was aimed to replace the alum type adjuvant for hepatitis B
      vaccine. The hepatitis B vaccine was encapsulated in poly (DL-lactide-co
      glycolide) microspheres by solvent evaporation technique. The formulated
      microspheres were characterized in terms of morphology, particle size analysis,
      in vitro release study and in vivo immune response in male Wistar rats. The FT IR
      spectrum illustrates the characteristics bands of poly (DL-lactide-co-glycolide)
      microspheres and hepatitis B vaccine at 1750 cm(-1) and 1650 cm(-1),
      respectively. The hepatitis B vaccine loaded poly (DL-lactide-co-glycolide)
      microspheres were able to release antigens till day 42. Significant enhancement
      of specific antibodies to HBsAg was produced till day 90 after a single
      administration of HBsAg encapsulated poly (DL-lactide-co-glycolide) microspheres.
      However, the conventional alum adsorbed hepatitis B vaccine was not found to
      produce any significant specific antibody levels till day 90 after a single dose.
      The results showed that poly (DL-lactide-co-glycolide) microspheres show
      potential as an adjuvant for hepatitis B vaccine.

PMID- 20046777
TI  - Simultaneous RPHPLC Determination of Nitazoxanide and Ofloxacin in Combined
      Tablet Dosage Form.
AB  - A simple, precise, accurate, rapid and reproducible reverse phase high
      performance liquid chromatographic procedure was developed for simultaneous
      determination of nitazoxanide and ofloxacin in tablet dosage form at a single
      wavelength. The mobile phase used was a combination of acetonitrile:0.25M
      potassium dihydrogen phosphate buffer (80:20) with 0.5%v/v of triethylamine and
      the pH was adjusted to 2.5 by adding orthophosphoric acid. The detection of the
      combined dosage form was carried out at 320 nm and flow rate was set to 1ml/min.
      Linearity was obtained in the concentration range of 5 to 25 mug/ml of
      nitazoxanide and ofloxacin with correlation coefficients of 0.9987 and 0.9995,
      respectively. The results of the analysis were validated statistically and
      recovery studies confirmed the accuracy of the proposed method.

PMID- 20046778
TI  - RP-HPLC Estimation of Risperidone in Tablet Dosage Forms.
AB  - A simple, specific, accurate, and precise reverse phase liquid chromatographic
      method was developed and validated for the estimation of risperidone in tablet
      dosage forms. A Phenomenex Gemini C-18, 5 mum column having 250x4.6 mm i.d. in
      isocratic mode, with mobile phase containing methanol: acetonitrile: 50 mM
      potassium dihydrogen orthophosphate (80:10:10 v/v) was used. The flow rate was
      1.3 ml/min and effluents were monitored at 234 nm. Clozapine was used as an
      internal standard. The retention time of risperidone and clozapine were 2.5 min
      and 3.3 min, respectively. The method was validated for linearity, accuracy,
      precision, specificity, limit of quantification, limit of detection, robustness
      and stability. The limit of detection and limit of quantification for estimation
      of risperidone was found to be 500 ng/ml and 990 ng/ml, respectively. Recovery of
      risperidone was found to be in the range of 99.02-101.68%. Proposed method was
      successfully applied for the quantitative determination of risperidone in tablet
      formulations.

PMID- 20046779
TI  - Formulation development and release studies of indomethacin suppositories.
AB  - Indomethacin suppositories were prepared by using water-soluble and oil soluble
      suppository bases, and evaluated for in vitro release by USP I and modified
      continuous flow through bead bed apparatus. Effect of the Tween 80 (1% and 5%)
      was further studied on in vitro release of the medicament. Release rate was good
      in water-soluble suppositories bases in comparison to oil soluble suppositories
      bases. Release was found to be greater in modified continuous flow through bead
      bed apparatus. When surfactant was used in low concentration then release rate
      was much greater, as compared to high concentration. When stability studies were
      performed on the prepared indomethacin suppositories it was found that
      suppositories made by water-soluble base had no significant changes while
      suppositories prepared by oil soluble bases, had some signs of instability.

PMID- 20046780
TI  - Spectrofluorimetric method for determination of duloxetine hydrochloride in bulk
      and pharmaceutical dosage forms.
AB  - A simple accurate, sensitive and reproducible spectrofluorimetric method was
      developed for the analysis of duloxetine hydrochloride in pure and pharmaceutical
      dosage form. Duloxetine hydrochloride showed strong native fluorescence in 0.05 M
      acetic acid having excitation at 225 nm and emission at 340 nm. Effect of
      different solvents were thoroughly investigated. The calibration graph was linear
      in the range from 0.020 to 0.400 mug/ml. The proposed method was statistically
      validated and successfully applied for analysis of capsule dosage forms. The
      limit of detection and limit of quantification were found to be 0.003 mug/ml and
      0.010 mug/ml, respectively. The percentage recovery was found to be in the range
      of 98.71% to 99.17%.

PMID- 20046781
TI  - Amlamax in the management of dyslipidemia in humans.
AB  - Hypercholesterolemia is the major cause of cardiovascular diseases leading to
      myocardial infarctions leading to considerable morbidity and mortality. During
      the past decade a group of molecules referred to as statins such as simvastatin,
      atrovastatin have been tried with great success in reducing total cholesterol.
      These molecules act by inhibiting the HMG CoA reductase enzyme thereby
      interfering with the synthesis of cholesterol. But statins reduce all the
      cholesterol including HDL cholesterol. Long term drug vigilance activity has
      revealed serious side effects of tendinopathy and related musculoskeletal
      disorders in some of the subjects. In an effort to manage hypercholesterolemia
      without serious side effects in a natural way we had tried the use of Amlamax a
      reconstituted, purified, standardized dried extract of amla (Emblica officinalis)
      containing 30% ellagitannins with other hydrolysable tannins on humans. We report
      the hitherto unobserved significant elevation of HDL cholesterol by the
      administration of Amlamax.

PMID- 20046782
TI  - Spectrophotometric determination of certain benzimidazole proton pump inhibitors.
AB  - Spectrophotometric method for the determination of certain proton pump inhibitors
      belonging to the benzimidazole class of compounds has been developed. The method
      is based on the reaction of omeprazole, lansoprazole, pantoprazole, rabeprazole
      and esomeprazole with iron (III) and subsequent reaction with ferricyanide under
      neutral condition which yields Prussian blue product with maximum absorption at
      720-730 nm. The commonly encountered excipients and additives that often
      accompany pharmaceutical preparations did not interfere with the determination.
      The method was applied for the determination of omeprazole, lansoprazole,
      pantoprazole, rabeprazole and esomeprazole in pharmaceutical preparations and no
      difference was found statistically. Thus, the spectrophotometric method can be
      applied as inexpensive, rapid, easy, accurate and precise method for the routine
      analysis of the five proton pump inhibitors in pharmaceutical preparations.

PMID- 20046783
TI  - New Spectrophotometric Method for Simultaneous determination of Metoprolol
      Tartarate and Hydrochlorthiazide in Tablets.
AB  - The present work describes a two-wavelength method for simultaneous determination
      of metoprolol and hydrochlorthiazide in fixed dose combination tablet. The
      wavelengths selected for method were 257.8 nm, 282.9 nm and 315.0 nm. The
      absorbance difference at first two wavelengths was used for determination of
      metoprolol and the latter was used for determination of hydrochlorthiazide. The
      recovery value for the drugs from the tablet matrix was found to be 100.55%
      (metoprolol) and 99.97% (comparison with standard) and 98.09% (E1%, 1cm) for
      hydrochlorthiazide. The method has an advantage that hydrochlorthiazide can be
      estimated in combination, as there is no interference of metoprolol at 315.0 nm.
      The method was evaluated statistically for its accuracy and precision.

PMID- 20046784
TI  - Simultaneous derivative spectrophotometric analysis of doxylamine succinate,
      pyridoxine hydrochloride and folic Acid in combined dosage forms.
AB  - Two UV spectrophotometric methods have been developed, based on first derivative
      spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine
      hydrochloride, and folic acid in tablet formulations. In method I, the
      concentrations of these drugs were determined by using linear regression
      equation. Method II is also based on first derivative spectrophotometry however
      simultaneous equations (Vierdot's method) were derived on derivative spectra. The
      first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for
      simultaneous estimation of these drugs respectively by both methods. In both the
      methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40
      mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and
      folic acid respectively. The developed methods show best results in terms of
      linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory
      mixtures of pure drugs and marketed formulations. The common excipients and
      additives did not interfere in their determinations.

PMID- 20046785
TI  - A New coumarin from Citrus paradisi Macf.
AB  - Phytochemical examination of the peel of grapefruit resulted in the isolation of
      five compounds namely friedelin, beta -sitosterol, 7(3',7',11',14'
      tetramethy)pentadec-2',6',10'-trienyloxycoumarin, limonin and cordialin B. These
      compounds have been characterized on the basis of spectral data, and
      7(3',7',11',14'-tetramethy)pentadec-2',6',10'-trienyloxycoumarin is a hitherto
      unreported compound.

PMID- 20046786
TI  - A simplified HPLC method for quantification of torsemide from human plasma and
      its application to a bioequivalence study.
AB  - A simple, rapid and selective method was developed. The method was validated and
      found to be linear in the range of 100-4000 ng/ml. Chromatographic peaks were
      separated by means of a 5 mum, C18 silica column using acetonitrile and phosphate
      buffer (0.05 M) in proportion of 40:60 (pH 4.0) as a mobile phase. The retention
      time of torsemide was 5.00+/-0.20 min. The chromatograms showed good resolution
      and no interference from plasma. The mean recovery from human plasma was found to
      be above 82%. Both inter-day and intra-day accuracy and precision data showed
      good reproducibility. This method was applied to a single dose bioequivalence
      study. Log transformed values were compared by ANOVA followed by classical 90%
      confidence interval. Confidence limits for C(max), AUC(0-t) and AUC(0-inf) ranged
      from 98.6 to 102.8, 101.8 to 105.3 and 102.4 to 105.5 respectively. These results
      suggested that the analytical method was linear, precise and accurate. Test and
      reference product were found to be bioequivalent.

PMID- 20046787
TI  - Essential Oil Composition and Antibacterial Studies of Vitex negundo Linn.
      Extracts.
AB  - Essential oils from fresh leaves, flowers and dried fruits of Vitex negundo were
      obtained by hydrodistillation. Using Soxhlet extractor five successive extracts
      from dried and powdered leaves were also taken. The chemical constituents of
      essential oil of leaves, flowers and dried fruits were analyzed by GC-FID and
      GC/MS techniques. Main constituents identified in leaves oil were delta-guaiene,
      carryophyllene epoxide and ethyl-hexadecenoate; in flowers oil - alpha-selinene,
      germacren-4-ol, carryophyllene epoxide and (E)-nerolidol while fruit oil showed
      beta-selinene, alpha-cedrene, germacrene D and hexadecanoic acid as the main
      constituents. beta-Caryophyllene was only the constituent identified as common to
      all three oils. alpha-Guaiene and guaia-3,7-diene were identified as common
      constituents in leaf and dried fruit oil while leaf and flower oils showed p 
      cymene, valencene, caryophyllene epoxide and (E)-nerolidol as common constituent.
      All the essential oils and successive extracts were evaluated for antibacterial
      potential against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and
      Pseudomonas aeruginosa bacterial strains. Each of the essential oils and extracts
      were found to give promising results against B. subtilis and E. coli. Ethyl
      acetate and ethanol extracts showed prominent antibacterial activity against all
      the tested strains. Fruits and leaves oil were found to be most active against E.
      coli and S. aureus, respectively. Only flowers oil was found to be active against
      P. aeruginosa.

PMID- 20046788
TI  - Development of mouth dissolving tablets of clozapine using two different
      techniques.
AB  - Mouth dissolving tablets constitute an innovative dosage form that overcomes the
      problems of swallowing and provides a quick onset of action. In view of enhancing
      bioavailability an attempt has been made to study two different methods direct
      compression and sublimation in formulation of mouth dissolving tablets of
      clozapine. Total four formulations using various superdisintegrants and subliming
      agents were prepared. All prepared formulations were evaluated for physico
      chemical parameters. The formulations exhibited good disintegration properties
      with total disintegration time in the range of 25 to 35 s. Comparative evaluation
      of two methods showed direct compression method is a better alternative to
      sublimation method as its formulations rapidly disintegrate in oral cavity. In
      vitro cumulative percentage drug release for formulations prepared by direct
      compression with explotab superdisintegrants shows 99.79 while sublimation method
      using camphor 93.58 release in 12 min. Kinetic studies indicated that all the
      formulations followed first order release with diffusion mechanism.

PMID- 20046789
TI  - Validated HPTLC Method for Simultaneous Determination of Quinapril Hydrochloride
      and Hydrochlorothiazide in a Tablet Dosage Form.
AB  - Quinapril hydrochloride and hydrochlorothiazide were simultaneously determined by
      HPTLC in pharmaceutical formulations. The drugs were separated on silica gel 60
      F(254) plates using suitable combination of solvents as mobile phase. The
      validation parameters, tested in accordance with the requirements of ICH
      guidelines, prove the suitability of methods.

PMID- 20046790
TI  - Development and evaluation of oral controlled release chlorpheniramine-ion
      exchange resinate suspension.
AB  - An oral controlled release suspension of chlorpheniramine maleate was prepared
      using ion-exchange resin technology. A strong cation exchange resin Indion 244
      was utilized for the sorption of the drug and the drug resinates was evaluated
      for various physical and chemical parameters. The drug-resinate complex was
      microencapsulated with a polymer Eudragit RS 100 to further retard the release
      characteristics. Both the drug-resinate complex and microencapsulated drug
      resinate were suspended in a palatable aqueous suspension base and were evaluated
      for controlled release characteristic. Stability study indicated that elevated
      temperature did not alter the sustained release nature of the dosage form
      indicating that polymer membrane surrounding the core material remained intact
      throughout the storage period.

PMID- 20046791
TI  - Synthesis, Anticonvulsant, Antimicrobial and Analgesic activity of Novel 1,2,4
      Dithiazoles.
AB  - A series of 1,2,4-dithiazole were synthesized from 1,2,4-thiadiazoles in the
      presence of CS(2) and evaluated for their antimicrobial, anticonvulsant,
      analgesic and neurotoxicity potential. The compounds provided significant
      protection against maximal electroshock-induced seizures and seizures induced by
      300 mg/kg of subcutaneous pentylenetetrazole administration. The designed
      compounds (3a-g) were screened in vitro for antibacterial activity against
      Staphylococcus aureus Escherichia coli, Bacillus subtilis and Pseudomonas
      aeruginosa and antifungal activity in fungal strains of Candida albicans and
      Aspergillus niger. Synthesized compounds exhibited moderate antibacterial and
      antifungal activity. N,N -Di-naphthalen-1-yl-N -(thioxo-5H -[1,2,4]dithiazol-3
      yl)-guanidine and N,N -Bis-(4-fluoro-phenyl)-N -(5-thioxo-5H -[1,2,4]dithiazol-3
      yl)-guanidine showed analgesic activity by tail flick method.

PMID- 20046792
TI  - Formulation and evaluation of exotic fat based cosmeceuticals for skin repair.
AB  - Mango butter was explored as a functional, natural supplement and active skin
      ingredient in skin care formulations. A foot care cream was developed with mango
      butter to evaluate its medicinal value and protective function in skin repair.
      Qualitative comparison and clinical case studies of the product were carried out.
      Wound healing potential of foot care cream was investigated on the rat excision
      and incision wound models. Results of the clinical studies demonstrated complete
      repair of worn and cracked skin in all the human volunteers. Furthermore, foot
      care cream exhibited significant healing response in both the wound models. The
      project work could be concluded as establishment of high potential for mango
      butter to yield excellent emolliency for better skin protection. Improving the
      product features and medicinal functionality further validate mango butter as a
      specialty excipient in development of cosmeceuticals and has an immense value for
      its commercialization.

PMID- 20046793
TI  - Development and validation of a simultaneous HPLC method for estimation of
      bisoprolol fumarate and amlodipine besylate from tablets.
AB  - A fast, robust and stability indicating RP-HPLC method was developed for
      simultaneous determination of bisoprolol fumarate and amlodipine besylate in
      tablets. The mobile phase was mixture of 25 mM ammonium acetate adjusted to pH
      5.0 and methanol (65: 35) at 0.8 ml/min. The stationary phase was Luna C18-2
      column (3 mu, 50x4.6 mm ID). UV detection was performed at 230 nm. Retention time
      was 1.45 min and 3.91 min for bisoprolol and amlodipine, respectively. Linearity
      was established in the range of 8-33 mug/ml. Mean recovery was 99.1% and 98.6%
      for bisoprolol fumarate and amlodipine besylate, respectively.

PMID- 20046794
TI  - Towards a framework for the elicitation of dilemmas.
AB  - This paper covers the main findings of the doctoral research that was concerned
      with seeking to extend aspects of dilemma theory. In professional practice, the
      Trompenaars Hampden-Turner Dilemma Reconciliation Process(TM) is a vehicle
      delivering dilemma theory in application. It informs a manager or leader on how
      to explore the dilemmas they face, how to reconcile the tensions that result, and
      how to structure the action steps for implementing the reconciled solutions. This
      vehicle forms the professional practice of the author who seeks to bring more
      rigor to consulting practice and thereby also contribute to theory development in
      the domain. The critical review of dilemma theory reveals that previous authors
      are inconsistent and variously invalid in their use of the terms 'dilemma
      theory,' 'dilemma methodology,' 'dilemma process,' 'dilemma reconciliation,'
      etc., and therefore an attempt is made to resolve these inconsistencies by
      considering whether 'dilemmaism' at the meta-level might be positioned as a new
      paradigm of inquiry for (management) research that embodies ontological,
      epistemological, and methodical premises that frame an approach to the resolution
      of real world business problems in (multi) disciplinary; (multi) functional and
      (multi) cultural business environments. This research offers contributions to
      knowledge, professional practice and theory development from the exploration of
      the SPID model as a way to make the elicitation of dilemmas more rigorous and
      structured and in the broader context of exploring 'dilemmaism' as a new paradigm
      of inquiry.

PMID- 20046795
TI  - The Relationship Between Receptivity to Media Models of Smoking and Nicotine
      Dependence Among South African Adolescents.
AB  - The purpose of this study is to determine the association of receptivity to media
      models of smoking and nicotine dependence among South African adolescents from
      four ethnic groups. A stratified random sample of 731 adolescents aged 12 to 17
      years (mean=14. 55, SD=1.68) was drawn from Johannesburg, South Africa. A
      structured questionnaire was administered to the participants in their homes by
      trained interviewers. Receptivity to media models of smoking was assessed with a
      three-item Likert scale. The dependent variable, nicotine dependence, was
      assessed with the Fagerstrom Test for Nicotine Dependence (FTND). Regression
      analyses showed a positive relationship between media receptivity and nicotine
      dependence, with control on demographic variables and hours of TV watched by the
      adolescent. This relationship was found to be strongest among White adolescents
      and weakest among Black adolescents. Though equally receptive to media models of
      smoking, Black adolescents have lower FTND scores than their peers from other
      South African ethnic groups. This may be related to the low prevalence of images
      in South Africa depicting Black people smoking cigarettes. Cultural norms against
      smoking among Black adolescents may also serve as a protective factor.

PMID- 20046796
TI  - Investigation of Depth of Interaction Encoding for a Pixelated LSO Array with a
      Single Multi-Channel PMT.
AB  - A new approach to depth of interaction (DOI) encoding for a pixelated LSO array
      using a single multi-channel PMT was investigated. In this method the DOI
      information was estimated by taking advantage of optical crosstalk between LSO
      elements and examining the standard deviation (spread) of signals on all channels
      of the PMT. Unpolished and polished 6*6 LSO arrays with a crystal size of
      1.3*1.3*20 mm(3) were evaluated on a Hamamatsu H7546 64-channel PMT. The arrays
      were placed on the center of the PMT and the central 16 channels of the PMT were
      individually read out and digitized. For the unpolished array, all crystals were
      resolved in the flood histogram. An average DOI resolution of 8 mm was obtained.
      The energy resolution was ~25% after the signal amplitude was corrected using the
      measured DOI information. For the polished array, the flood histogram was
      superior to the unpolished array, however no DOI information could be measured.
      Using unpolished crystals, this method could be a practical way to achieve
      limited DOI information in PET detectors. The standard deviation of all PMT
      channels can be readily obtained using a resistor network. Only five signals
      (four signals to determine the x-y position and one signal measuring the standard
      deviation) need to be digitized, and this method only requires a single photon
      detector to read out the array. Unlike phoswich detectors, the method does not
      require segmenting the scintillator array into layers. The measured DOI
      resolution was much worse than that obtained with the dual-ended readout method,
      however, it was similar to that obtained with a two-layer phoswich detector.

PMID- 20046797
TI  - Efficient Constrained Local Model Fitting for Non-Rigid Face Alignment.
AB  - Active appearance models (AAMs) have demonstrated great utility when being
      employed for non-rigid face alignment/tracking. The "simultaneous" algorithm for
      fitting an AAM achieves good non-rigid face registration performance, but has
      poor real time performance (2-3 fps). The "project-out" algorithm for fitting an
      AAM achieves faster than real time performance (> 200 fps) but suffers from poor
      generic alignment performance. In this paper we introduce an extension to a
      discriminative method for non-rigid face registration/tracking referred to as a
      constrained local model (CLM). Our proposed method is able to achieve superior
      performance to the "simultaneous" AAM algorithm along with real time fitting
      speeds (35 fps). We improve upon the canonical CLM formulation, to gain this
      performance, in a number of ways by employing: (i) linear SVMs as patch-experts,
      (ii) a simplified optimization criteria, and (iii) a composite rather than
      additive warp update step. Most notably, our simplified optimization criteria for
      fitting the CLM divides the problem of finding a single complex registration/warp
      displacement into that of finding N simple warp displacements. From these N
      simple warp displacements, a single complex warp displacement is estimated using
      a weighted least-squares constraint. Another major advantage of this simplified
      optimization lends from its ability to be parallelized, a step which we also
      theoretically explore in this paper. We refer to our approach for fitting the CLM
      as the "exhaustive local search" (ELS) algorithm. Experiments were conducted on
      the CMU Multi-PIE database.

PMID- 20046799
TI  - Guided Cell Migration on Microtextured Substrates with Variable Local Density and
      Anisotropy.
AB  - This work reports the design of and experimentation with a topographically
      patterned cell culture substrate of variable local density and anisotropy as a
      facile and efficient platform to guide the organization and migration of cells in
      spatially desirable patterns. Using UV-assisted capillary force lithography, an
      optically transparent microstructured layer of a UV curable poly(urethane
      acrylate) resin is fabricated and employed as a cell-culture substrate after
      coating with fibronectin. With variable local pattern density and anisotropy
      present in a single cell-culture substrate, the differential polarization of cell
      morphology and movement in a single experiment is quantitatively characterized.
      It is found that cell shape and velocity are exquisitely sensitive to variation
      in the local anisotropy of the two-dimensional rectangular lattice arrays, with
      cell elongation and speed decreasing on symmetric lattice patterns. It is also
      found that cells could integrate orthogonal spatial cues when determining the
      direction of cell orientation and movement. Furthermore, cells preferentially
      migrate toward the topographically denser areas from sparser ones. Consistent
      with these results, it is demonstrated that systematic variation of local
      densities of rectangular lattice arrays enable a planar assembly of cells into a
      specified location. It is envisioned that lithographically defined substrates of
      variable local density and anisotropy not only provide a new route to tailoring
      the cell-material interface but could serve as a template for advanced tissue
      engineering.

PMID- 20046798
TI  - Interventions to Improve Care for Patients with Limited Health Literacy.
AB  - OBJECTIVE: To propose a framework and describe best practices for improving care
      for patients with limited health literacy (LHL). METHODS: Review of the
      literature. RESULTS: Approximately half of the U.S. adult population has LHL.
      Because LHL is associated with poor health outcomes and contributes to health
      disparities, the adoption of evidence-based best practices is imperative.
      Feasible interventions at the clinician-patient level (eg, patient-centered
      communication, clear communication techniques, teach-to-goal methods, and
      reinforcement), at the system-patient level (eg, clear health education
      materials, visual aids, clear medication labeling, self-management support
      programs, and shame-free clinical environments), and at the community-patient
      level (eg, adult education referrals, lay health educators, and harnessing the
      mass media) can improve health outcomes for patients with LHL. CONCLUSION:
      Because LHL is prevalent, and because the recommended communication strategies
      can benefit patients of all literacy levels, clinicians, health system planners,
      and health policy leaders should promote the uptake of these strategies into
      routine care.

PMID- 20046800
TI  - Rapid Multi-Tracer PET Tumor Imaging With F-FDG and Secondary Shorter-Lived
      Tracers.
AB  - Rapid multi-tracer PET, where two to three PET tracers are rapidly scanned with
      staggered injections, can recover certain imaging measures for each tracer based
      on differences in tracer kinetics and decay. We previously showed that single
      tracer imaging measures can be recovered to a certain extent from rapid dual
      tracer (62)Cu - PTSM (blood flow) + (62)Cu - ATSM (hypoxia) tumor imaging. In
      this work, the feasibility of rapidly imaging (18)F-FDG plus one or two of these
      shorter-lived secondary tracers was evaluated in the same tumor model. Dynamic
      PET imaging was performed in four dogs with pre-existing tumors, and the raw scan
      data was combined to emulate 60 minute long dual- and triple-tracer scans, using
      the single-tracer scans as gold standards. The multi-tracer data were processed
      for static (SUV) and kinetic (K(1), K(net)) endpoints for each tracer, followed
      by linear regression analysis of multi-tracer versus single-tracer results.
      Static and quantitative dynamic imaging measures of FDG were both accurately
      recovered from the multi-tracer scans, closely matching the single-tracer FDG
      standards (R > 0.99). Quantitative blood flow information, as measured by PTSM
      K(1) and SUV, was also accurately recovered from the multi-tracer scans (R =
      0.97). Recovery of ATSM kinetic parameters proved more difficult, though the ATSM
      SUV was reasonably well recovered (R = 0.92). We conclude that certain additional
      information from one to two shorter-lived PET tracers may be measured in a rapid
      multi-tracer scan alongside FDG without compromising the assessment of glucose
      metabolism. Such additional and complementary information has the potential to
      improve tumor characterization in vivo, warranting further investigation of rapid
      multi-tracer techniques.

PMID- 20046801
TI  - Factorial Invariance and The Specification of Second-Order Latent Growth Models.
AB  - Latent growth modeling has been a topic of intense interest during the past two
      decades. Most theoretical and applied work has employed first-order growth
      models, in which a single manifest variable serves as indicator of trait level at
      each time of measurement. In the current paper, we concentrate on issues
      regarding second-order growth models, which have multiple indicators at each time
      of measurement. With multiple indicators, tests of factorial invariance of
      parameters across times of measurement can be tested. We conduct such tests using
      two sets of data, which differ in the extent to which factorial invariance holds,
      and evaluate longitudinal confirmatory factor, latent growth curve, and latent
      difference score models. We demonstrate that, if factorial invariance fails to
      hold, choice of indicator used to identify the latent variable can have
      substantial influences on the characterization of patterns of growth, strong
      enough to alter conclusions about growth. We also discuss matters related to the
      scaling of growth factors and conclude with recommendations for practice and for
      future research.

PMID- 20046802
TI  - The Analysis of Social Networks.
AB  - Many questions about the social organization of medicine and health services
      involve interdependencies among social actors that may be depicted by networks of
      relationships. Social network studies have been pursued for some time in social
      science disciplines, where numerous descriptive methods for analyzing them have
      been proposed. More recently, interest in the analysis of social network data has
      grown among statisticians, who have developed more elaborate models and methods
      for fitting them to network data. This article reviews fundamentals of, and
      recent innovations in, social network analysis using a physician influence
      network as an example. After introducing forms of network data, basic network
      statistics, and common descriptive measures, it describes two distinct types of
      statistical models for network data: individual-outcome models in which networks
      enter the construction of explanatory variables, and relational models in which
      the network itself is a multivariate dependent variable. Complexities in
      estimating both types of models arise due to the complex correlation structures
      among outcome measures.

PMID- 20046804
TI  - Inference in a Synchronization Game with Social Interactions.
AB  - This paper studies inference in a continuous time game where an agent's decision
      to quit an activity depends on the participation of other players. In
      equilibrium, similar actions can be explained not only by direct influences but
      also by correlated factors. Our model can be seen as a simultaneous duration
      model with multiple decision makers and interdependent durations. We study the
      problem of determining the existence and uniqueness of equilibrium stopping
      strategies in this setting. This paper provides results and conditions for the
      detection of these endogenous effects. First, we show that the presence of such
      effects is a necessary and sufficient condition for simultaneous exits. This
      allows us to set up a nonparametric test for the presence of such influences
      which is robust to multiple equilibria. Second, we provide conditions under which
      parameters in the game are identified. Finally, we apply the model to data on
      desertion in the Union Army during the American Civil War and find evidence of
      endogenous influences.

PMID- 20046803
TI  - On approximation of smooth functions from samples of partial derivatives with
      application to phase unwrapping.
AB  - This paper addresses the problem of approximating smooth bivariate functions from
      the samples of their partial derivatives. The approximation is carried out under
      the assumption that the subspace to which the functions to be recovered are
      supposed to belong, possesses an approximant in the form of a principal shift
      invariant (PSI) subspace. Subsequently, the desired approximation is found as the
      element of the PSI subspace that fits the data the best in the (2)-sense. In
      order to alleviate the ill-posedness of the process of finding such a solution,
      we take advantage of the discrete nature of the problem under consideration. The
      proposed approach allows the explicit construction of a projection operator which
      maps the measured derivatives into a stable and unique approximation of the
      corresponding function. Moreover, the paper develops the concept of discrete PSI
      subspaces, which may be of relevance for several practical settings where one is
      given samples of a function instead of its continuously defined values. As a
      final point, the application of the proposed method to the problem of phase
      unwrapping in homomorphic deconvolution is described.

PMID- 20046805
TI  - A NOVEL SURFACE-BASED GEOMETRIC APPROACH FOR 3D DENDRITIC SPINE DETECTION FROM
      MULTI-PHOTON EXCITATION MICROSCOPY IMAGES.
AB  - Determining the relationship between the dendritic spine morphology and its
      functional properties is a fundamental while challenging problem in neurobiology
      research. In particular, how to accurately and automatically analyze meaningful
      structural information from a large microscopy image dataset is far away from
      being resolved. In this paper, we propose a novel method for the automated neuron
      reconstruction and spine detection from fluorescence microscopy images. After
      image processing, backbone of the neuron is obtained and the neuron is
      represented as a 3D surface. Based on the analysis of geometric features on the
      surface, spines are detected by a novel hybrid of two segmentation methods.
      Besides the automated detection of spines, our algorithm is able to extract
      accurate 3D structures of spines. Comparison results between our approach and the
      state of the art shows that our algorithm is more accurate and robust, especially
      for detecting and separating touching spines.

PMID- 20046806
TI  - Insomnia In Caregivers Of Persons With Dementia: Who Is At Risk And What Can Be
      Done About It?
AB  - Sleep problems are associated with mood and function disturbances in caregivers
      of persons with Alzheimer's disease (AD). However, the factors associated with
      the onset and maintenance of sleep disturbances in caregivers of persons with
      dementia are unknown, and little attention has been paid to treatments to improve
      sleep in caregivers. Here we review some of the evidence for the association
      between caregiver sleep problems, and caregiver and care-recipient demographic,
      health, and psychosocial variables. We present data from a longitudinal study
      that examined factors associated with self-reported sleep problems in dementia
      caregivers and care-recipients over a 5-year follow-up period, and describe the
      existing caregiver insomnia treatment literature. We conclude with
      recommendations for future research.

PMID- 20046807
TI  - A K-alpha x-ray source using high energy and high repetition rate laser system
      for phase contrast imaging.
AB  - K-alpha x-ray sources from laser produced plasmas provide completely new
      possibilities for x-ray phase-contrast imaging applications. By tightly focusing
      intense femtosecond laser pulses onto a solid target K-alpha x-ray pulses are
      generated through the interaction of energetic electrons created in the plasma
      with the bulk target. In this paper, we present a continuous and efficient Mo K
      alpha x-ray source produced by a femtosecond laser system operating at 100 Hz
      repetition rate with maximum pulse energy of 110 mJ before compression. The
      source has an x-ray conversion efficiency of greater than 10(-5) into K-alpha
      line emission. In preparation for phase contrast imaging applications, the size
      of the resultant K-alpha x-ray emission spot has been also characterized. The
      source exhibits sufficient spatial coherence to observe phase contrast. We
      observe a relatively small broadening of the K-alpha source size compared to the
      size of the laser beam itself. Detailed characterization of the source including
      the x-ray spectrum and the x-ray average yield along with phase contrast images
      of test objects will be presented.

PMID- 20046808
TI  - Development of ultrafast laser-based x-ray in-vivo phase-contrast micro-CT
      beamline for biomedical applications at Advanced Laser Light Source (ALLS).
AB  - We are developing and exploring the imaging performance of, an in vivo, in-line
      holography, x-ray phase-contrast, micro-CT system with an ultrafast laser-based x
      ray (ULX) source. By testing and refining our system, and by performing computer
      simulations, we plan to improve system performance in terms of contrast
      resolution and multi-energy imaging to a level beyond what can be obtained using
      a conventional microfocal x-ray tube. Initial CT projection sets at single energy
      (Mo K(alpha) and K(beta) lines) were acquired in the Fresnel regime and
      reconstructed for phantoms and a euthanized mouse. We also performed computer
      simulations of phase-contrast micro-CT scans for low-contrast, soft-tissue, tumor
      imaging. We determined that, in order to perform a phase-contrast, complete micro
      CT scan using ULX, the following conditions must be met: (i) the x-ray source
      needs to be stable during the scan; (ii) the laser focal spot size needs to be
      less than 10 mum for source-to-object distance greater than 30 cm; (iii) the
      laser light intensity on the target needs to be in the range of 5 x 10(17) to 5 x
      10(19) W/cm(2); (iv) the ablation protection system needs to allow uninterrupted
      scans; (v) the laser light focusing on the target needs to remain accurate during
      the entire scan; (vi) a fresh surface of the target must be exposed to
      consecutive laser shots during the entire scan; (vii) the effective detector
      element size must be less than 12 mum. Based on the results obtained in this
      research project, we anticipate that the new 10 Hz, 200 TW laser with 50 W
      average power that is being commissioned at ALLS will allow us practical
      implementation of in vivo x-ray phase-contrast micro-CT.

PMID- 20046809
TI  - The Private Market for Long-Term Care Insurance in the U.S.: A Review of the
      Evidence.
AB  - This paper reviews the growing literature on the market for private long-term
      care insurance, a market notable for its small size despite the fact that long
      term care expenses are potentially large and highly uncertain. After summarizing
      long-term care utilization and insurance coverage in the United States, the paper
      reviews research on the supply of and the demand for private long-term care
      insurance. It concludes that demand-side factors impose important limits on the
      size of the private market and that we currently have a limited understanding of
      how public policies could be designed to encourage the growth of this market.

PMID- 20046810
TI  - On the Role of Goal Dysregulation in the Treatment of Bipolar Disorder.
AB  - Nusslock, Abramson, Harmon-Jones, Alloy, and Coan (this issue) propose that
      current psychosocial treatments for bipolar disorder be supplemented with
      interventions focused on altering goal dysregulation pathways. While innovations
      to existing treatment manuals are always welcome, there are several reasons why
      this suggestion may require further consideration. We highlight issues pertaining
      to the status of cognitive-behavioral therapy for bipolar disorder, the
      distinction between education and psychoeducation, the nature of familial
      expressed emotion, differences between clinical and analog samples, and the
      larger question of how to assess mechanisms in psychosocial treatment studies. We
      also raise the question of whether an optimistic goal orientation can be a
      protective factor in patients' long-term coping with bipolar disorder.

PMID- 20046811
TI  - Blind Pedestrians and the Changing Technology and Geometry of Signalized
      Intersections: Safety, Orientation, and Independence.
AB  - This study documented that blind pedestrians have considerable difficulty
      locating crosswalks, aligning to cross, determining the onset of the walk
      interval, maintaining a straight crossing path, and completing crossings before
      the onset of perpendicular traffic at complex signalized intersections. Revised
      techniques and strategies are suggested for alleviating these difficulties.

PMID- 20046812
TI  - HIV vaccination: turning the spotlight on effector memory T cells as mucosal
      gatekeepers.
AB  - The accumulating failures in HIV vaccine development demonstrate that the
      immunization approaches used so far are insufficient to reproduce the naturally
      occurring immunity that controls the virus in long-term non-progressors, HIV
      controllers, and continuously exposed sex workers. They also underscore the
      desperate need for new approaches in the design of more effective vaccination
      protocols. Recent findings might have brought us closer to that goal by providing
      proof of concept for a novel preventative HIV vaccine by establishing CD8
      effector memory T cells within the mucosal sites of transmission.

PMID- 20046813
TI  - The Scaffolded Mind: Higher mental processes are grounded in early experience of
      the physical world.
AB  - It has long been a staple of psychological theory that early life experiences
      significantly shape the adult's understanding of and reactions to the social
      world. Here we consider how early concept development along with evolved motives
      operating early in life can come to exert a passive, unconscious influence on the
      human adult's higher-order goal pursuits, judgments, and actions. In particular,
      we focus on concepts and goal structures specialized for interacting with the
      physical environment (e.g., distance cues, temperature, cleanliness, and self
      protection), which emerge early and automatically as a natural part of human
      development and evolution. It is proposed that via the process of scaffolding,
      these early sensorimotor experiences serve as the foundation for the later
      development of more abstract concepts and goals. Experiments using priming
      methodologies reveal the extent to which these early concepts serve as the
      analogical basis for more abstract psychological concepts, such that we come
      easily and naturally to speak of close relationships, warm personalities, moral
      purity, and psychological pain. Taken together, this research demonstrates the
      extent to which such foundational concepts are capable of influencing people's
      information processing, affective judgments, and goal pursuit, oftentimes outside
      of their intention or awareness.

PMID- 20046814
TI  - Bronchiectasis, part 2: Management.
AB  - Systemic antibiotics are the mainstay of the management of acute exacerbations of
      bronchiectasis. Antibiotic selection should include coverage for Streptococcus
      pneumoniae and Haemophilus influenzae; particular attention also should be paid
      to the presence of Staphylococcus aureus and Pseudomonas species. The duration of
      antibiotic therapy is not well-established, but most clinicians recommend a
      prolonged course, often longer than 3 weeks. There is some evidence that long
      term low-dose macrolide therapy can reduce the incidence of acute exacerbations
      and decrease sputum production. There also may be a role for the use of inhaled
      antibiotics. Airway clearance strategies, such as chest percussion and postural
      drainage, are clearly useful in patients with cystic fibrosis and may be useful
      in other patients with bronchiectasis. Surgical resection can be considered if a
      patient has localized disease that is refractory to medical management or if
      he/she is unwilling to undergo long-term medical therapy.

PMID- 20046815
TI  - [HIV/AIDS and Breastfeeding.]
AB  - HIV/AIDS is a pandemic that affects men, women and children, but is increasingly
      affecting women, especially among reproductive age. This has consequences over
      vertical transmission during pregnancy, delivery or breastfeeding. This analysis
      describes the relation between HIV/AIDS and breastfeeding, and the factors that
      influence the decision mothers living with HIV/AIDS make about the feeding
      modality they will choose. Also, causes of infant mortality in relation with this
      problem are described in accordance with international recommendations to prevent
      mother to child transmission. In this environment where globalization takes
      place, constant migrations have created a need for health care workers to
      consider social factors that influence the decision of women living with HIV/AIDS
      in relation with feeding options for their infants. It is not enough to know the
      proven risk for HIV/AIDS transmission through breastfeeding, there is a need to
      be conscious about the dynamic and specific factors each community has.

PMID- 20046816
TI  - Parental Monitoring, Religious Involvement and Drug Use Among Latino and Non
      Latino Youth in the Southwestern United States.
AB  - AIMS: The purpose of this study was to examine parental monitoring practices and
      religious involvement (protective factors) and substance use among Mexican
      American and Non-Latino adolescents in the Southwest of the United States.
      FRAMEWORK: We also relied on social control theories to guide our investigation
      of why adolescents may choose not to use drugs. PARTICIPANTS: The sample was
      N=1087 adolescents, the age ranged from 13 to 15 years, and the gender
      distribution was approximately equal. There were 71% Mexican Americans and 29%
      non-Latinos in the sample. METHODS: a number of measures were used including
      recent substance use, religiosity, religious affiliation, parental monitoring,
      parental permissiveness, parental norms, and acculturation. Linear regressions
      were used to examine the relationship between the variables of interest and the
      outcomes. RESULTS: Although the effect sizes of the significant relationships
      were modest, the findings are of interest because they reinforce the importance
      of the role of parents in the lives of their adolescents and supports previous
      studies that find that parents have great influence on children's behaviors
      including substance use. The results suggest that acculturating adolescents
      benefit from having clear rules from their parents concerning substance use, and
      from believing that there is some kind of consequence attached to their behavior.
      Parental monitoring, by itself, did not explain lower levels of drug use among
      these adolescents; but it was a predictor of adolescent strong anti-drug personal
      norms. This study is useful to social workers and other professionals working
      with parents and adolescents as it provides concrete evidence of possible parents
      pathway of influence on their children's health status.

PMID- 20046817
TI  - First-Grade Predictors of Mathematical Learning Disability: A Latent Class
      Trajectory Analysis.
AB  - Kindergarten to 3(rd) grade mathematics achievement scores from a prospective
      study of mathematical development were subjected to latent growth trajectory
      analyses (n = 306). The four corresponding classes included children with
      mathematical learning disability (MLD, 6% of sample), and low (LA, 50%),
      typically (TA, 39%) and high (HA, 5%) achieving children. The groups were
      administered a battery of intelligence (IQ), working memory, and mathematical
      cognition measures in 1(st) grade. The children with MLD had general deficits in
      working memory and IQ, and potentially more specific deficits on measures of
      number sense. The LA children did not have working memory or IQ deficits, but
      showed moderate deficits on these number sense measures and for addition fact
      retrieval. The distinguishing features of the HA children were a strong
      visuospatial working memory, a strong number sense, and frequent use of memory
      based processes to solve addition problems. Implications for the early
      identification of children at risk for poor mathematics achievement are
      discussed.

PMID- 20046818
TI  - Driving and Age-Related Macular Degeneration.
AB  - This article reviews the research literature on driving and age-related macular
      degeneration, which is motivated by the link between driving and the quality of
      life of older adults and their increased collision rate. It addresses the risk of
      crashes, driving performance, driving difficulty, self-regulation, and
      interventions to enhance, safety, and considers directions for future research.

PMID- 20046819
TI  - QUANTITATIVE MAGNETIC RESONANCE IMAGE ANALYSIS VIA THE EM ALGORITHM WITH
      STOCHASTIC VARIATION.
AB  - Quantitative Magnetic Resonance Imaging (qMRI) provides researchers insight into
      pathological and physiological alterations of living tissue, with the help of
      which, researchers hope to predict (local) therapeutic efficacy early and
      determine optimal treatment schedule. However, the analysis of qMRI has been
      limited to ad-hoc heuristic methods. Our research provides a powerful statistical
      framework for image analysis and sheds light on future localized adaptive
      treatment regimes tailored to the individual's response. We assume in an
      imperfect world we only observe a blurred and noisy version of the underlying
      pathological/physiological changes via qMRI, due to measurement errors or
      unpredictable influences. We use a hidden Markov Random Field to model the
      spatial dependence in the data and develop a maximum likelihood approach via the
      Expectation-Maximization algorithm with stochastic variation. An important
      improvement over previous work is the assessment of variability in parameter
      estimation, which is the valid basis for statistical inference. More importantly,
      we focus on the expected changes rather than image segmentation. Our research has
      shown that the approach is powerful in both simulation studies and on a real
      dataset, while quite robust in the presence of some model assumption violations.

PMID- 20046820
TI  - PROCESS FLOW FOR CLASSIFICATION AND CLUSTERING OF FRUIT FLY GENE EXPRESSION
      PATTERNS.
AB  - The rapidly growing collection of fruit fly embryo images makes automated Image
      Segmentation and classification an indispensable requirement for a large-scale
      analysis of in situ hybridization (ISH) - gene expression patterns (GEP). We
      present here such an automated process flow for Segmenting, Classification, and
      Clustering large-scale sets of Drosophila melanogaster GEP that is capable of
      dealing with most of the complications implicated in the images.

PMID- 20046821
TI  - Functional and structural changes in the chinchilla cochlea and vestibular system
      following round window application of carboplatin.
AB  - OBJECTIVE: In chinchillas, moderate doses of carboplatin administered
      systemically selectively destroy inner hair cells and type I vestibular hair
      cells; however, it is unclear whether this unique damage pattern persists if
      carboplatin is applied directly to the cochlea, how quickly the damage develops
      and what cell death pathways are involved. STUDY DESIGN: To address these
      questions, carboplatin (5 mg/ml, 50 ul) was applied to the round window. RESULTS:
      Carboplatin caused a rapid decline in distortion product otoacoustic emissions,
      significantly increased compound action potential thresholds and caused massive
      inner hair cell loss and less severe outer hair cell loss. Hair cell loss was
      initially more severe in the base than the apex of the cochlea, but by 28 days
      post-treatment most cochlear hair cells were missing and hair cell density in the
      utricle, saccule and lateral crista was greatly reduced. At one day post
      treatment, many hair cell nuclei were condensed or fragmented indicative of
      apoptosis, and expressed initiator caspase-8 and executioner caspase-3, but not
      initiator caspase-9. Carboplatin-treated animals circled towards the treated ear
      and during the swim test rolled towards the treated ear. CONCLUSION: These
      results indicate that local application of carboplatin causes loss of hair cells
      that begins near the base of the cochlea and spreads towards the apex with
      increasing survival time. Hair cell loss is initiated by caspase-8 followed by
      executioner caspase-3.

PMID- 20046822
TI  - HOW ACCURATELY CAN A SINGLE MOLECULE BE LOCALIZED WHEN IMAGED THROUGH AN OPTICAL
      MICROSCOPE?
AB  - We present a simple analytical expression for the fundamental limit to the
      accuracy with which the location of a single molecule can be determined that is
      imaged through an optical microscope. This expression depends on the optical
      properties of the microscope and the photophysical properties of the single
      molecule. We also show how the fundamental limit is deteriorated by factors like
      pixelation of the detector and noise sources in the detection system. The present
      results gives an experimenter insight into what is achievable in an optical
      microscope and provide guidelines for experimental design.

PMID- 20046823
TI  - Easy Multiplicity Control in Equivalence Testing Using Two One-sided Tests.
AB  - Equivalence testing is growing in use in scientific research outside of its
      traditional role in the drug approval process. Largely due to its ease of use and
      recommendation from the United States Food and Drug Administration guidance, the
      most common statistical method for testing equivalence is the two one-sided tests
      procedure (TOST). Like classical point-null hypothesis testing, TOST is subject
      to multiplicity concerns as more comparisons are made. In this manuscript, a
      condition that bounds the family-wise error rate using TOST is given. This
      condition then leads to a simple solution for controlling the family-wise error
      rate. Specifically, we demonstrate that if all pair-wise comparisons of k
      independent groups are being evaluated for equivalence, then simply scaling the
      nominal Type I error rate down by (k - 1) is sufficient to maintain the family
      wise error rate at the desired value or less. The resulting rule is much less
      conservative than the equally simple Bonferroni correction. An example of
      equivalence testing in a non drug-development setting is given.

PMID- 20046824
TI  - Self-reported and actual beta-blocker prescribing for heart failure patients:
      physician predictors.
AB  - BACKGROUND: Beta-blockers reduce mortality among patients with systolic heart
      failure (HF), yet primary care provider prescription rates remain low. OBJECTIVE:
      To examine the association between primary care physician characteristics and
      both self-reported and actual prescription of beta-blockers among patients with
      systolic HF. DESIGN: Cross-sectional survey with supplementary retrospective
      chart review. PARTICIPANTS: Primary care providers at three New York City
      Veterans Affairs medical centers. MEASUREMENTS: MAIN OUTCOMES WERE: 1) self
      reported prescribing of beta-blockers, and 2) actual prescribing of beta-blockers
      among HF patients. Physician HF practice patterns and confidence levels, as well
      as socio-demographic and clinical characteristics, were also assessed. RESULTS:
      Sixty-nine of 101 physicians (68%) completed the survey examining self-reported
      prescribing of beta-blockers. Physicians who served as inpatient ward attendings
      self-reported significantly higher rates of beta-blocker prescribing among their
      HF patients when compared with physicians who did not attend (78% vs. 58%; p =
      0.002), as did physicians who were very confident in managing HF patients when
      compared with physicians who were not (82% vs. 68%; p = 0.009). Fifty-one of
      these 69 surveyed physicians (74%) were successfully matched to 287 HF patients
      for whom beta-blocker prescribing data was available. Physicians with greater
      self-reported rates of prescribing beta-blockers were significantly more likely
      to actually prescribe beta-blockers (p = 0.02); however, no other physician
      characteristics were significantly associated with actual prescribing of beta
      blockers among HF patients. CONCLUSIONS: Physician teaching responsibilities and
      confidence levels were associated with self-reported beta-blocker prescribing
      among their HF patients. Educational efforts focused on improving confidence
      levels in HF care and increasing exposure to teaching may improve beta-blocker
      presciption in HF patients managed in primary care.

PMID- 20046825
TI  - Abnormal placental development and early embryonic lethality in EpCAM-null mice.
AB  - BACKGROUND: EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a
      variety of normal and malignant epithelial cells and some leukocytes. Results of
      previous in vitro experiments suggested that EpCAM is an intercellular adhesion
      molecule. EpCAM has been extensively studied as a potential tumor marker and
      immunotherapy target, and more recent studies suggest that EpCAM expression may
      be characteristic of cancer stem cells. METHODOLOGY/PRINCIPAL FINDINGS: To gain
      insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an
      embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene
      trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2
      exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable
      and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/-
      embryos revealed that betageo was expressed in several epithelial structures
      including developing ears (otocysts), eyes, branchial arches, gut, apical
      ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice
      died in utero by E12.5, and were small, developmentally delayed, and displayed
      prominent placental abnormalities. In developing placentas, EpCAM was expressed
      throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas
      of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking
      prominent vascularity. Parietal trophoblast giant cells were also dramatically
      reduced in EpCAM -/- placentas. CONCLUSION: EpCAM was required for
      differentiation or survival of parietal trophoblast giant cells, normal
      development of the placental labyrinth and establishment of a competent maternal
      fetal circulation. The findings in EpCAM-reporter mice suggest involvement of
      this molecule in development of vital organs including the gut, kidneys,
      pancreas, lungs, eyes, and limbs.

PMID- 20046826
TI  - The temporal dynamics of implicit processing of non-letter, letter, and word
      forms in the human visual cortex.
AB  - The decoding of visually presented line segments into letters, and letters into
      words, is critical to fluent reading abilities. Here we investigate the temporal
      dynamics of visual orthographic processes, focusing specifically on right
      hemisphere contributions and interactions between the hemispheres involved in the
      implicit processing of visually presented words, consonants, false fonts, and
      symbolic strings. High-density EEG was recorded while participants detected
      infrequent, simple, perceptual targets (dot strings) embedded amongst a of
      character strings. Beginning at 130 ms, orthographic and non-orthographic stimuli
      were distinguished by a sequence of ERP effects over occipital recording sites.
      These early latency occipital effects were dominated by enhanced right-sided
      negative-polarity activation for non-orthographic stimuli that peaked at around
      180 ms. This right-sided effect was followed by bilateral positive occipital
      activity for false-fonts, but not symbol strings. Moreover the size of components
      of this later positive occipital wave was inversely correlated with the right
      sided ROcc180 wave, suggesting that subjects who had larger early right-sided
      activation for non-orthographic stimuli had less need for more extended bilateral
      (e.g., interhemispheric) processing of those stimuli shortly later. Additional
      early (130-150 ms) negative-polarity activity over left occipital cortex and
      longer-latency centrally distributed responses (>300 ms) were present, likely
      reflecting implicit activation of the previously reported 'visual-word-form' area
      and N400-related responses, respectively. Collectively, these results provide a
      close look at some relatively unexplored portions of the temporal flow of
      information processing in the brain related to the implicit processing of
      potentially linguistic information and provide valuable information about the
      interactions between hemispheres supporting visual orthographic processing.

PMID- 20046827
TI  - Neuroanatomical correlates of developmental dyscalculia: combined evidence from
      morphometry and tractography.
AB  - Poor mathematical abilities adversely affect academic and career opportunities.
      The neuroanatomical basis of developmental dyscalculia (DD), a specific learning
      deficit with prevalence rates exceeding 5%, is poorly understood. We used
      structural MRI and diffusion tensor imaging (DTI) to examine macro- and micro
      structural impairments in 7- to 9-year-old children with DD, compared to a group
      of typically developing (TD) children matched on age, gender, intelligence,
      reading abilities and working memory capacity. Voxel-based morphometry (VBM)
      revealed reduced grey matter (GM) bilaterally in superior parietal lobule, intra
      parietal sulcus, fusiform gyrus, parahippocampal gyrus and right anterior
      temporal cortex in children with DD. VBM analysis also showed reduced white
      matter (WM) volume in right temporal-parietal cortex. DTI revealed reduced
      fractional anisotropy (FA) in this WM region, pointing to significant right
      hemisphere micro-structural impairments. Furthermore, FA in this region was
      correlated with numerical operations but not verbal mathematical reasoning or
      word reading. Atlas-based tract mapping identified the inferior longitudinal
      fasciculus, inferior fronto-occipital fasciculus and caudal forceps major as key
      pathways impaired in DD. DTI tractography suggests that long-range WM projection
      fibers linking the right fusiform gyrus with temporal-parietal WM are a specific
      source of vulnerability in DD. Network and classification analysis suggest that
      DD in children may be characterized by multiple dysfunctional circuits arising
      from a core WM deficit. Our findings link GM and WM abnormalities in children
      with DD and they point to macro- and micro-structural abnormalities in right
      hemisphere temporal-parietal WM, and pathways associated with it, as key
      neuroanatomical correlates of DD.

PMID- 20046828
TI  - Disease gene characterization through large-scale co-expression analysis.
AB  - BACKGROUND: In the post genome era, a major goal of biology is the identification
      of specific roles for individual genes. We report a new genomic tool for gene
      characterization, the UCLA Gene Expression Tool (UGET). RESULTS: Celsius, the
      largest co-normalized microarray dataset of Affymetrix based gene expression, was
      used to calculate the correlation between all possible gene pairs on all
      platforms, and generate stored indexes in a web searchable format. The size of
      Celsius makes UGET a powerful gene characterization tool. Using a small seed list
      of known cartilage-selective genes, UGET extended the list of known genes by
      identifying 32 new highly cartilage-selective genes. Of these, 7 of 10 tested
      were validated by qPCR including the novel cartilage-specific genes SDK2 and
      FLJ41170. In addition, we retrospectively tested UGET and other gene expression
      based prioritization tools to identify disease-causing genes within known linkage
      intervals. We first demonstrated this utility with UGET using genetically
      heterogeneous disorders such as Joubert syndrome, microcephaly, neuropsychiatric
      disorders and type 2 limb girdle muscular dystrophy (LGMD2) and then compared
      UGET to other gene expression based prioritization programs which use small but
      discrete and well annotated datasets. Finally, we observed a significantly higher
      gene correlation shared between genes in disease networks associated with similar
      complex or Mendelian disorders. DISCUSSION: UGET is an invaluable resource for a
      geneticist that permits the rapid inclusion of expression criteria from one to
      hundreds of genes in genomic intervals linked to disease. By using thousands of
      arrays UGET annotates and prioritizes genes better than other tools especially
      with rare tissue disorders or complex multi-tissue biological processes. This
      information can be critical in prioritization of candidate genes for sequence
      analysis.

PMID- 20046829
TI  - Optimal cytoplasmic transport in viral infections.
AB  - For many viruses, the ability to infect eukaryotic cells depends on their
      transport through the cytoplasm and across the nuclear membrane of the host cell.
      During this journey, viral contents are biochemically processed into complexes
      capable of both nuclear penetration and genomic integration. We develop a
      stochastic model of viral entry that incorporates all relevant aspects of
      transport, including convection along microtubules, biochemical conversion,
      degradation, and nuclear entry. Analysis of the nuclear infection probabilities
      in terms of the transport velocity, degradation, and biochemical conversion rates
      shows how certain values of key parameters can maximize the nuclear entry
      probability of the viral material. The existence of such "optimal" infection
      scenarios depends on the details of the biochemical conversion process and
      implies potentially counterintuitive effects in viral infection, suggesting new
      avenues for antiviral treatment. Such optimal parameter values provide a
      plausible transport-based explanation of the action of restriction factors and of
      experimentally observed optimal capsid stability. Finally, we propose a new
      interpretation of how genetic mutations unrelated to the mechanism of drug action
      may nonetheless confer novel types of overall drug resistance.

PMID- 20046831
TI  - Parameter identifiability and redundancy in a general class of stochastic
      carcinogenesis models.
AB  - BACKGROUND: Heidenreich et al. (Risk Anal 1997 17 391-399) considered parameter
      identifiability in the context of the two-mutation cancer model and demonstrated
      that combinations of all but two of the model parameters are identifiable. We
      consider the problem of identifiability in the recently developed carcinogenesis
      models of Little and Wright (Math Biosci 2003 183 111-134) and Little et al. (J
      Theoret Biol 2008 254 229-238). These models, which incorporate genomic
      instability, generalize a large number of other quasi-biological cancer models,
      in particular those of Armitage and Doll (Br J Cancer 1954 8 1-12), the two
      mutation model (Moolgavkar et al. Math Biosci 1979 47 55-77), the generalized
      multistage model of Little (Biometrics 1995 51 1278-1291), and a recently
      developed cancer model of Nowak et al. (PNAS 2002 99 16226-16231).
      METHODOLOGY/PRINCIPAL FINDINGS: We show that in the simpler model proposed by
      Little and Wright (Math Biosci 2003 183 111-134) the number of identifiable
      combinations of parameters is at most two less than the number of biological
      parameters, thereby generalizing previous results of Heidenreich et al. (Risk
      Anal 1997 17 391-399) for the two-mutation model. For the more general model of
      Little et al. (J Theoret Biol 2008 254 229-238) the number of identifiable
      combinations of parameters is at most less than the number of biological
      parameters, where is the number of destabilization types, thereby also
      generalizing all these results. Numerical evaluations suggest that these bounds
      are sharp. We also identify particular combinations of identifiable parameters.
      CONCLUSIONS/SIGNIFICANCE: We have shown that the previous results on parameter
      identifiability can be generalized to much larger classes of quasi-biological
      carcinogenesis model, and also identify particular combinations of identifiable
      parameters. These results are of theoretical interest, but also of practical
      significance to anyone attempting to estimate parameters for this large class of
      cancer models.

PMID- 20046830
TI  - Mechanisms of c-myc degradation by nickel compounds and hypoxia.
AB  - Nickel (Ni) compounds have been found to cause cancer in humans and animal models
      and to transform cells in culture. At least part of this effect is mediated by
      stabilization of hypoxia inducible factor (HIF1a) and activating its downstream
      signaling. Recent studies reported that hypoxia signaling might either antagonize
      or enhance c-myc activity depending on cell context. We investigated the effect
      of nickel on c-myc levels, and demonstrated that nickel, hypoxia, and other
      hypoxia mimetics degraded c-myc protein in a number of cancer cells (A549, MCF-7,
      MDA-453, and BT-474). The degradation of the c-Myc protein was mediated by the
      26S proteosome. Interestingly, knockdown of both HIF-1alpha and HIF-2alpha
      attenuated c-Myc degradation induced by Nickel and hypoxia, suggesting the
      functional HIF-1alpha and HIF-2alpha was required for c-myc degradation. Further
      studies revealed two potential pathways mediated nickel and hypoxia induced c-myc
      degradation. Phosphorylation of c-myc at T58 was significantly increased in cells
      exposed to nickel or hypoxia, leading to increased ubiquitination through Fbw7
      ubiquitin ligase. In addition, nickel and hypoxia exposure decreased USP28, a c
      myc de-ubiquitinating enzyme, contributing to a higher steady state level of c
      myc ubiquitination and promoting c-myc degradation. Furthermore, the reduction of
      USP28 protein by hypoxia signaling is due to both protein degradation and
      transcriptional repression. Nickel and hypoxia exposure significantly increased
      the levels of dimethylated H3 lysine 9 at the USP28 promoter and repressed its
      expression. Our study demonstrated that Nickel and hypoxia exposure increased c
      myc T58 phosphorylation and decreased USP28 protein levels in cancer cells, which
      both lead to enhanced c-myc ubiquitination and proteasomal degradation.

PMID- 20046833
TI  - Large Numbers of Matings Give Female Field Crickets a Direct Benefit but not a
      Genetic Benefit.
AB  - Female crickets can potentially gain both direct and indirect benefits from
      mating multiple times with different males. Most studies have only examined the
      effects of small numbers of matings, although female crickets are capable of
      mating many times. The goal of this paper is to examine the direct and indirect
      benefits of mating large numbers of times for female reproductive success. In a
      previous experiment, female Gryllus vocalis were found to gain diminishing direct
      benefits from mating large numbers of times. In this study I attempt to determine
      whether mating large numbers of times yields similar diminishing returns on
      female indirect benefits. Virgin female Gryllus vocalis crickets were assigned to
      mate five, ten or 15 times with either the same or different males. Females that
      mated more times gained direct benefits in terms of laying more eggs and more
      fertilized eggs. Females that mated with different males rather than mating
      repeatedly with the same male did not have higher offspring hatching success, a
      result that is contrary to other published results comparing female reproductive
      success with repeated versus different partners. These results suggest that
      females that mate large numbers of times fail to gain additional genetic benefits
      from doing so.

PMID- 20046834
TI  - On Association Coefficients for 2x2 Tables and Properties That Do Not Depend on
      the Marginal Distributions.
AB  - We discuss properties that association coefficients may have in general, e.g.,
      zero value under statistical independence, and we examine coefficients for 2x2
      tables with respect to these properties. Furthermore, we study a family of
      coefficients that are linear transformations of the observed proportion of
      agreement given the marginal probabilities. This family includes the phi
      coefficient and Cohen's kappa. The main result is that the linear transformations
      that set the value under independence at zero and the maximum value at unity,
      transform all coefficients in this family into the same underlying coefficient.
      This coefficient happens to be Loevinger's H.

PMID- 20046832
TI  - Avicin D, a plant triterpenoid, induces cell apoptosis by recruitment of Fas and
      downstream signaling molecules into lipid rafts.
AB  - Avicins, a family of triterpene electrophiles originally identified as potent
      inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that
      also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We
      previously showed that Jurkat cells, which express a high level of Fas, are very
      sensitive to treatment with avicins. Thus, we hypothesized that avicins may
      induce cell apoptosis by activation of the Fas pathway. By using a series of cell
      lines deficient in cell death receptors, we demonstrated that upon avicin D
      treatment, Fas translocates to the cholesterol- and sphingolipid-enriched
      membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts
      with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing
      signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid
      raft organization by using a cholesterol-depleting compound, methyl-beta
      cyclodextrin, not only prevents the clustering of Fas and its DISC complex but
      also reduces the sensitivity of the cells to avicin D. Avicin D activates Fas
      pathways independent of the association between extracellular Fas ligands and Fas
      receptors. A deficiency in Fas and its downstream signaling molecules leads to
      the resistance of the cells to avicin D treatment. Taken together, our results
      demonstrate that avicin D triggers the redistribution of Fas in the membrane
      lipid rafts, where Fas activates receptor-mediated cell death.

PMID- 20046835
TI  - A Note on "Constant Latent Odds-Ratios Models and the Mantel-Haenszel Null
      Hypothesis" Hessen, 2005.
AB  - In a recent paper, Hessen (Psychometrika 70(3):497-516, 2005) introduces the
      class of constant latent odds-ratios models as an extension of the Rasch model
      for which the sum score is still the sufficient statistic for ability. In this
      paper the relation between both the general and the general parametric constant
      latent odds-ratios model and the Rasch model is considered.

PMID- 20046836
TI  - Family Functioning and Low Vision: A Systematic Review.
AB  - This review highlights the literature on the function and adjustment process of
      family members of persons with adult-onset vision loss. The majority of the
      literature has focused on the unique role that the family plays in providing both
      instrumental and emotional support to adults with low vision. In contrast, the
      impact of low vision on the psychosocial adjustment of the family has been
      largely understudied. The review concludes with a discussion of the implications
      for clinical practice, along with directions for future research on the family
      within the context of low vision rehabilitation.

PMID- 20046838
TI  - Powered Sit-to-Stand and Assistive Stand-to-Sit Framework for a Powered
      Transfemoral Prosthesis.
AB  - This work extends the three level powered knee and ankle prosthesis control
      framework previously developed by the authors by adding sitting mode. A middle
      level finite state based impedance controller is designed to accommodate sitting,
      sit-to-stand and stand-to-sit transitions. Moreover, a high level Gaussian
      Mixture Model based intent recognizer is developed to distinguish between
      standing and sitting modes and switch the middle level controllers accordingly.
      Experimental results with unilateral transfemoral amputee subject show that
      sitting down and standing up intent can be inferred from the prosthesis sensor
      signals by the intent recognizer. Furthermore, it is demonstrated that the
      prosthesis generates net active power of 50 W during standing up and dissipates
      up to 50 W of power during stand-to-sit transition at the knee joint.

PMID- 20046837
TI  - P19 H-ras induces G1/S phase delay maintaining cells in a reversible quiescence
      state.
AB  - BACKGROUND: Three functional c-ras genes, known as c-H-ras, c-K-ras, and c-N-ras,
      have been largely studied in mammalian cells with important insights into normal
      and tumorigenic cellular signal transduction events. Two K-Ras mRNAs are obtained
      from the same pre-mRNA by alternative splicing. H-Ras pre-mRNA can also be
      alternatively spliced in the IDX and 4A terminal exons, yielding the p19 and p21
      proteins, respectively. However, despite the Ras gene family's established role
      in tumorigenic cellular signal transduction events, little is known about p19
      function. Previous results showed that p19 did not interact with two known p21
      effectors, Raf1 and Rin1, but was shown to interact with RACK1, a scaffolding
      protein that promotes multi-protein complexes in different signaling pathways
      (Cancer Res 2003, 63 p5178). This observation suggests that p19 and p21 play
      differential and complementary roles in the cell. PRINCIPAL FINDINGS: We found
      that p19 regulates telomerase activity through its interaction with p73alpha/beta
      proteins. We also found that p19 overexpression induces G1/S phase delay; an
      observation that correlates with hypophosphorylation of both Akt and p70SK6.
      Similarly, we also observed that FOXO1 is upregulated when p19 is overexpressed.
      The three observations of (1) hypophosphorylation of Akt, (2) G1/S phase delay
      and (3) upregulation of FOXO1 lead us to conclude that p19 induces G1/S phase
      delay, thereby maintaining cells in a reversible quiescence state and preventing
      entry into apoptosis. We then assessed the effect of p19 RNAi on HeLa cell growth
      and found that p19 RNAi increases cell growth, thereby having the opposite effect
      of arrest of the G1/S phase or producing a cellular quiescence state.
      SIGNIFICANCE: Interestingly, p19 induces FOXO1 that in combination with the G1/S
      phase delay and hypophosphorylation of both Akt and p70SK6 leads to maintenance
      of a reversible cellular quiescence state, thereby preventing entry into
      apoptosis.

PMID- 20046839
TI  - Hyperbolic planforms in relation to visual edges and textures perception.
AB  - We propose to use bifurcation theory and pattern formation as theoretical probes
      for various hypotheses about the neural organization of the brain. This allows us
      to make predictions about the kinds of patterns that should be observed in the
      activity of real brains through, e.g., optical imaging, and opens the door to the
      design of experiments to test these hypotheses. We study the specific problem of
      visual edges and textures perception and suggest that these features may be
      represented at the population level in the visual cortex as a specific second
      order tensor, the structure tensor, perhaps within a hypercolumn. We then extend
      the classical ring model to this case and show that its natural framework is the
      non-Euclidean hyperbolic geometry. This brings in the beautiful structure of its
      group of isometries and certain of its subgroups which have a direct
      interpretation in terms of the organization of the neural populations that are
      assumed to encode the structure tensor. By studying the bifurcations of the
      solutions of the structure tensor equations, the analog of the classical Wilson
      and Cowan equations, under the assumption of invariance with respect to the
      action of these subgroups, we predict the appearance of characteristic patterns.
      These patterns can be described by what we call hyperbolic or H-planforms that
      are reminiscent of Euclidean planar waves and of the planforms that were used in
      previous work to account for some visual hallucinations. If these patterns could
      be observed through brain imaging techniques they would reveal the built-in or
      acquired invariance of the neural organization to the action of the corresponding
      subgroups.

PMID- 20046840
TI  - Applications of calendar instruments in social surveys: a review.
AB  - Retrospective reports in survey interviews and questionnaires are subject to many
      types of recall error, which affect completeness, consistency, and dating
      accuracy. Concerns about this problem have led to the development of so-called
      calendar instruments, or timeline techniques. These aided recall procedures have
      been designed to help respondents gain better access to long-term memory by
      providing a graphical time frame in which life history information can be
      represented. In order to obtain more insights into the potential benefits of
      calendar methodology, this paper presents a review of the application of calendar
      instruments, their design characteristics and effects on data quality. Calendar
      techniques are currently used in a variety of fields, including life course
      research, epidemiology and family planning studies. Despite the growing interest
      in these new methods, their application often lacks sufficient theoretical
      foundation and little attention has been paid to their effectiveness. Several
      recent studies however, have demonstrated that in comparison to more traditional
      survey methods, calendar techniques can improve some aspects of data quality.
      While calendar instruments have been shown to be potentially beneficial to
      retrospective data quality, there is an apparent need for methodological research
      that generates more systematic knowledge about their application in social
      surveys.

PMID- 20046841
TI  - Thurstonian-Based Analyses: Past, Present, and Future Utilities.
AB  - Current psychometric models of choice behavior are strongly influenced by
      Thurstone's (1927, 1931) experimental and statistical work on measuring and
      scaling preferences. Aided by advances in computational techniques, choice models
      can now accommodate a wide range of different data types and sources of
      preference variability among respondents induced by such diverse factors as
      person-specific choice sets or different functional forms for the underlying
      utility representations. At the same time, these models are increasingly
      challenged by behavioral work demonstrating the prevalence of choice behavior
      that is not consistent with the underlying assumptions of these models. I discuss
      new modeling avenues that can account for such seemingly inconsistent choice
      behavior and conclude by emphasizing the interdisciplinary frontiers in the study
      of choice behavior and the resulting challenges for psychometricians.

PMID- 20046842
TI  - Erratum to: Immune maintenance in glaucoma: boosting the body's own
      neuroprotective potential.
AB  - Glaucoma, a slow progressive neurodegenerative disorder associated with death of
      retinal ganglion cells and degeneration of their connected optic nerve fibers,
      has been classically linked to high intraocular pressure. Regardless of the
      primary risk factor, degeneration may continue, resulting in further loss of
      neurons and subsequent glaucomatous damage. During the past decade, scientists
      and clinicians began to accept that, in addition or as an alternative to fighting
      off the primary risk factor(s), there is a need to protect the tissue from the
      ongoing spread of damage-an approach collectively termed "neuroprotection." We
      found that the immune system, the body's own defense mechanism, plays a key role
      in the ability of the optic nerve and the retina to withstand glaucomatous
      conditions. This defense involves recruitment of both innate and adaptive immune
      cells that together create a protective niche and thereby halt disease
      progression. The spontaneous immune response might not be sufficient, and
      therefore, we suggest boosting it by immunization (with the appropriate antigen,
      at specific timing and predetermined optimal dosing) which may be developed into
      a suitable therapeutic vaccination to treat glaucoma. This view of immune system
      involvement in glaucoma will raise new challenges in glaucoma research, changing
      the way in which clinicians perceive the disease and the approach to
      therapy.[This corrects the article on p. in vol. .].

PMID- 20046844
TI  - Erratum: An experiment of the combined treatment of traditional Lei-huo-jiu
      therapy with Chinese medicine for the lacrimal gland of Sjogren's syndrome.
AB  - This experiment chooses nonobese diabetic (NOD) mouse as the animal model of
      Sjogren's syndrome and investigates the morphologic changes, the expression of
      inflammatory factors and growth factors of this mouse's lacrimal gland in
      response to a combined treatment of traditional Lei-huo-jiu therapy alone and in
      combination with Chinese medicine. The methods were to (1) use a morphological
      approach to directly observe pathological changes of the lacrimal gland in
      response to combined treatment and (2) to detect the level of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1, and nuclear factor kappa B (NF-kappaB) in
      lacrimal gland tissue caused by the combined treatments using a
      immunohistochemical approach. There is a reduction of the mast cell's
      degranulation and modulation of the level of cytokines in TNF-alpha, IL-1, and NF
      kappaB in the combined therapy group. The combined treatment of traditional Lei
      huo-jiu therapy with Chinese medicine can improve the pathological changes of the
      lacrimal gland tissue of the NOD mouse through modulating the level of TNF-alpha,
      IL-1, and NF-kappaB which results in improved tear secretion and function of the
      lacrimal gland.[This corrects the article on p. in vol. .].

PMID- 20046843
TI  - Erratum: Psychoneuroimmunology: application to ocular diseases.
AB  - Psychoneuroimmunology (PNI) is a relatively new discipline within the field of
      neuroscience which researches the relationship between emotional states, the
      central and peripheral nervous systems, and the endocrine and immune systems.
      Negative psychological states, such as stress, anxiety, and depression, may alter
      immune system regulation and modulation of peripheral cytokines. A plethora of
      PNI studies have shown that increased psychological stress and depression are
      associated with an alteration of immune functioning and worsened health outcomes
      for many conditions. To date, application of PNI methodology has not been
      reported for ocular diseases. This article provides an historical perspective on
      the origins of the rift between the emotional and spiritual from physical aspects
      of disease. A review of how stress is mediated through sympathetic
      adrenomedullary and hypothalamic pituitary axis activation with shifts in
      immunity is provided. The literature which supports spirituality in healing is
      presented. Finally, ocular diseases which would be most amenable to a PNI
      approach are discussed.[This corrects the article on p. in vol. .].

PMID- 20046845
TI  - Erratum: Modulation of microglia by Wolfberry on the survival of retinal ganglion
      cells in a rat ocular hypertension model.
AB  - The active component of Wolfberry (Lycium barbarum), lycium barbarum
      polysaccharides (LBP), has been shown to be neuroprotective to retinal ganglion
      cells (RGCs) against ocular hypertension (OH). Aiming to study whether this
      neuroprotection is mediated via modulating immune cells in the retina, we used
      multiphoton confocal microscopy to investigate morphological changes of microglia
      in whole-mounted retinas. Retinas under OH displayed slightly activated
      microglia. One to 100 mg/kg LBP exerted the best neuroprotection and elicited
      moderately activated microglia in the inner retina with ramified appearance but
      thicker and focally enlarged processes. Intravitreous injection of bacterial
      endotoxin lipopolysaccharide (LPS) decreased the survival of RGCs at 4 weeks, and
      the activated microglia exhibited amoeboid appearance as fully activated
      phenotype. When activation of microglia was attenuated by intravitreous injection
      of macrophage/microglia inhibitory factor, protective effect of 10 mg/kg LBP was
      attenuated. The results implicated that neuroprotective effects of LBP were
      partly due to modulating the activation of microglia.[This corrects the article
      on p. in vol. .].

PMID- 20046846
TI  - Erratum: The two sides of cytokine signaling and glaucomatous optic neuropathy.
AB  - The mechanistic study of glaucoma pathogenesis has shifted to seeking to
      understand the effects of immune responses on retinal ganglion cell damage and
      protection. Cytokines are the hormonal factors that mediate most of the
      biological effects in both the immune and nonimmune systems. CD4-expressing T
      helper cells are a major source of cytokine production and regulation. Type 1
      helper T (Th1) cells are characterized by the production of proinflammatory
      cytokines such as interferon-gamma, interleukin (IL)-2, IL-12, IL-23, and tumor
      necrosis factor-alpha while type 2 helper T (Th2) cells are characterized by the
      production of IL-4, IL-5, IL-6, and IL-10. The balance of Th1/Th2 cytokine
      production influences many pathological processes and plays both causative and
      protective roles in neuronal damage. Growing evidence indicates that imbalances
      of Th1/Th2 cytokine production are involved in neural damage or protection in
      many neurological diseases. In this review, we discuss the possible roles of
      Th1/Th2 cytokine production and imbalance of Th1/Th2 cytokines in retina,
      especially glaucomatous optic neuropathy.[This corrects the article on p. in vol.
      .].

PMID- 20046847
TI  - Mitochondria and the regulation of free radical damage in the eye.
AB  - Neuronal cell death can be determined by the overall level of reactive oxygen
      species (ROS) resulting from the combination of extrinsic sources and intrinsic
      production as a byproduct of oxidative phosphorylation. Key controllers of the
      intrinsic production of ROS are the mitochondrial uncoupling proteins (UCPs). By
      allowing a controlled leak of protons across the inner mitochondrial membrane
      activation of these proteins can decrease ROS and promote cell survival. In both
      primate models of Parkinson's disease and mouse models of seizures, increased
      activity of UCP2 significantly increased neuronal cells survival. In the retina
      UCP2 is expressed in many neurons and glial cells, but was not detected in rod
      photoreceptors. Retinal ganglion cell survival following excitotoxic damage was
      much greater in animals overexpressing UCP2. Traditional Chinese medicines, such
      as an extract of Cistanche tubulosa, may provide benefit by altering
      mitochondrial metabolism.

PMID- 20046849
TI  - Introduction: complementary medicine in ophthalmology.

PMID- 20046850
TI  - The Assumption of Proportional Components when Candecomp is Applied to Symmetric
      Matrices in the Context of Indscal.
AB  - The use of Candecomp to fit scalar products in the context of INDSCAL is based on
      the assumption that the symmetry of the data matrices involved causes the
      component matrices to be equal when Candecomp converges. Ten Berge and Kiers gave
      examples where this assumption is violated for Gramian data matrices. These
      examples are believed to be local minima. It is now shown that, in the single
      component case, the assumption can only be violated at saddle points. Chances of
      Candecomp converging to a saddle point are small but still nonzero.

PMID- 20046848
TI  - Erratum: Neural protection by naturopathic compounds-an example of
      tetramethylpyrazine from retina to brain.
AB  - Given the advantages of being stable in the ambient environment, being permeable
      to the blood-brain and/or blood-eye barriers and being convenient for
      administration, naturopathic compounds have growingly become promising
      therapeutic candidates for neural protection. Extracted from one of the most
      common Chinese herbal medicines, tetramethylpyrazine (TMP), also designated as
      ligustrazine, has been suggested to be neuroprotective in the central nervous
      system as well as the peripheral nerve network. Although the detailed molecular
      mechanisms of its efficacy for neural protection are understood limitedly,
      accumulating evidence suggests that antioxidative stress, antagonism for calcium,
      and suppression of pro-inflammatory factors contribute significantly to its
      neuroprotection. In animal studies, systemic administration of TMP (subcutaneous
      injection, 50 mg/kg) significantly blocked neuronal degeneration in hippocampus
      as well as the other vulnerable regions in brains of Sprague-Dawley rats
      following kainate-induced prolonged seizures. Results from us and others also
      demonstrated potent neuroprotective efficacy of TMP for retinal cells and robust
      benefits for brain in Alzheimer's disease or other brain injury. These results
      suggest a promising prospect for TMP to be used as a treatment of specific
      neurodegenerative diseases. Given the assessment of the distribution, metabolism,
      excretion, and toxicity information that is already available on most
      neuroprotective naturopathic compounds such as TMP, preclinical data to justify
      bringing such therapeutic compounds to clinical trials in humans is
      feasible.[This corrects the article on p. in vol. .].

PMID- 20046851
TI  - Mokken Scale Analysis for Dichotomous Items Using Marginal Models.
AB  - Scalability coefficients play an important role in Mokken scale analysis. For a
      set of items, scalability coefficients have been defined for each pair of items,
      for each individual item, and for the entire scale. Hypothesis testing with
      respect to these scalability coefficients has not been fully developed. This
      study introduces marginal modelling as a framework to derive the standard errors
      for the scaling coefficients and test hypotheses about these coefficients.
      Several examples demonstrate the possibilities of marginal modelling in Mokken
      scale analysis. These possibilities include testing whether Mokken's criteria for
      a scale are satisfied, testing whether scalability coefficients of different
      items are equal, and testing whether scalability coefficients are equal across
      different groups.

PMID- 20046853
TI  - Latent Class Models for Diary Method Data: Parameter Estimation by Local
      Computations.
AB  - The increasing use of diary methods calls for the development of appropriate
      statistical methods. For the resulting panel data, latent Markov models can be
      used to model both individual differences and temporal dynamics. The
      computational burden associated with these models can be overcome by exploiting
      the conditional independence relations implied by the model. This is done by
      associating a probabilistic model with a directed acyclic graph, and applying
      transformations to the graph. The structure of the transformed graph provides a
      factorization of the joint probability function of the manifest and latent
      variables, which is the basis of a modified and more efficient E-step of the EM
      algorithm. The usefulness of the approach is illustrated by estimating a latent
      Markov model involving a large number of measurement occasions and, subsequently,
      a hierarchical extension of the latent Markov model that allows for transitions
      at different levels. Furthermore, logistic regression techniques are used to
      incorporate restrictions on the conditional probabilities and to account for the
      effect of covariates. Throughout, models are illustrated with an experience
      sampling methodology study on the course of emotions among anorectic patients.

PMID- 20046852
TI  - Bile acids in treatment of ocular disease.
AB  - Bear bile has been included in Asian pharmacopeias for thousands of years in
      treatment of several diseases, ranging from sore throat to hemorrhoids. The
      hydrophilic bile acids tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid
      (UDCA) are the major bile acids of bear bile. Both of these are available as
      synthetic formulations and are approved by the health administrations of several
      countries for treatment of cirrhosis and gallstones. This review briefly covers
      the use of bear bile in Traditional Chinese Medicine, bile acid physiology,
      approved use of UDCA and TUDCA in Western medicine, and recent research exploring
      their neuroprotective properties, including in models of ocular disease.

PMID- 20046854
TI  - Vertical distribution and diel patterns of zooplankton abundance and biomass at
      Conch Reef, Florida Keys (USA).
AB  - Zooplankton play an important role in the trophic dynamics of coral reef
      ecosystems. Detailed vertical and temporal distribution and biomass of
      zooplankton were evaluated at four heights off the bottom and at six times
      throughout the diel cycle over a coral reef in the Florida Keys (USA).
      Zooplankton abundance averaged 4396 +/- 1949 SD individuals m(-3), but temporal
      and spatial distributions varied for individual zooplankton taxa by time of day
      and by height off the bottom. Copepods comprised 93-96% of the abundance in the
      samples. Taxon-based zooplankton CHN values paired with abundance data were used
      to estimate biomass. Average daily biomass ranged from 3.1 to 21.4 mg C m(-3) and
      differed by both height off the bottom and by time of day. While copepods were
      the numerically dominant organisms, their contribution to biomass was only 35% of
      the total zooplankton biomass. Our findings provide important support for the new
      emerging paradigm of how zooplankton are distributed over reefs.

PMID- 20046855
TI  - Heterogeneous films of ionotropic hydrogels fabricated from delivery templates of
      patterned paper.
AB  - The use of delivery templates makes it possible to fabricate shaped, millimeter
      thick heterogeneously patterned films of ionotropic hydrogels. These structures
      include two-dimensional (2-D) patterns of a polymer cross-linked by different
      ions (e.g., alginic acid cross-linked with Ca2+ and Fe3+) and patterns of step
      gradients in the concentration of a single cross-linking ion. The delivery
      templates consist of stacked sheets of chromatography paper patterned with
      hydrophobic barriers (waterproof tape, transparency film, or toner deposited by a
      color laser printer). Each layer of paper serves as a reservoir for a different
      solution of cross-linking ions, while the hydrophobic barriers prevent solutions
      on adjacent sheets from mixing. Holes cut through the sheets expose different
      solutions of cross-linking ions to the surface of the templates. Films with
      shaped regions of hydrogels cross-linked by paramagnetic ions can be oriented
      with a bar magnet. Variations in the concentrations of cations used to cross-link
      the gel can control the mechanical properties of the film: for single alginate
      films composed of areas cross-linked with different concentrations of Fe3+, the
      regions cross-linked with high concentrations of Fe3+ are more rigid than regions
      cross-linked with low concentrations of Fe3+. The heterogeneous hydrogel films
      can be used to culture bacteria in various 2-D designs. The pattern of toxic and
      nontoxic ions used to cross-link the polymer determines the pattern of viable
      colonies of Escherichia coli within the film.

PMID- 20046856
TI  - Linking speech errors and phonological grammars: Insights from Harmonic Grammar
      networks.
AB  - Phonological grammars characterize distinctions between relatively well-formed
      (unmarked) and relatively ill-formed (marked) phonological structures. We review
      evidence that markedness influences speech error probabilities. Specifically,
      although errors result in both unmarked as well as marked structures, there is a
      markedness asymmetry: errors are more likely to produce unmarked outcomes. We
      show that stochastic disruption to the computational mechanisms realizing a
      Harmonic Grammar (HG) can account for the broad empirical patterns of speech
      errors. We demonstrate that our proposal can account for the general markedness
      asymmetry. We also develop methods for linking particular HG proposals to speech
      error distributions, and illustrate these methods using a simple HG and a set of
      initial consonant errors in English.

PMID- 20046857
TI  - A Historical Perspective of the Understanding of the Link between Diet and
      Coronary Heart Disease.
AB  - The development of the understanding of the underlying causes of coronary heart
      disease has undergone several stages. Ecological studies, such as the Seven
      Countries' Study, showed a possible relationship between mortality in coronary
      heart disease and intake of saturated fats. The investigated area with the lowest
      rates of cardiovascular disease was the island of Crete, Greece. A discussion
      soon started to evolve around the Mediterranean diet, which at the time consisted
      of mainly foods of vegetable origin, olive oil and cereals of unrefined nature.
      Several clinical trials have been undertaken since, including the Lyon Heart Diet
      Study where it was clearly shown that both mortality and morbidity in coronary
      heart disease was substantially lowered by Mediterranean food compared to
      controls. Dean Ornish proved that an extreme regimen actually could reduce
      already existing sclerotic plaques, while the WHI study showed that a more modest
      diet change diet not cause the intended reduction in heart disease in middle-aged
      women. Another prospective study of a similar age group of women showed that a
      diet with a low glycemic load gave a good reduction in coronary heart disease.
      Multiple studies of different components of food have shown no positive result,
      pointing at the whole diet rather than its components of nutrients being of
      importance. Today, the experts agree on the optimal diet to prevent not only
      heart disease but also cancer forms and other chronic disease such as type 2
      diabetes mellitus. This diet is consisting of a lot of fruit and vegetables, lots
      of fish, less salt and sugar, more unrefined cereals, beans and nuts. Going from
      a general notion of Mediterranean food to testing that food in clinical settings
      and testing nutrients as preventative agents, we can conclude that a generally
      healthy lifestyle, including a healthy diet, appropriate amounts of physical
      activity, good sleep and less stress, is the way to a heart healthy life.

PMID- 20046858
TI  - Building Emotional Resilience to Promote Health.
AB  - In recent years, a growing body of evidence has linked positive emotional health
      with lower cardiovascular morbidity and mortality, independent of negative
      emotion. Several potential mechanisms have been posited to account for these
      associations, including improved health behavior, direct physiological benefits,
      and enhanced resistance to and recovery from stress among individuals with high
      versus low positive emotional resources. Links between positive emotion and
      health have implications for targeted interventions, but no empirical
      investigations to date have tested the impact of efforts to enhance positive
      emotion on cardiovascular risk. Nevertheless, some existing data point to the
      potential value of strategies to increase emotional resources for individuals'
      functional health and capacity to manage stress.

PMID- 20046859
TI  - Examining Trends in Adolescent Environmental Attitudes, Beliefs, and Behaviors
      Across Three Decades.
AB  - Since the Environmental Movement began, adolescents' views have been largely
      ignored in studies of public opinion. The article presents a descriptive analysis
      of trends in the environmental attitudes, beliefs, and behaviors of high school
      seniors from 1976 to 2005 using data from the Monitoring the Future study. Across
      a range of indicators, environmental concerns of adolescents show increases
      during the early 1990s and declines across the remainder of the three decades.
      Declining trends in reports of personal responsibility for the environment,
      conservation behaviors, and the belief that resources are scarce are particularly
      noteworthy. Across all years, findings reveal that youth tended to assign
      responsibility for the environment to the government and consumers rather than
      accepting personal responsibility. Recent declines in environmental concerns for
      this nationally representative sample of youth signal the need for a renewed
      focus on young people's views and call for better environmental education and
      governmental leadership.

PMID- 20046861
TI  - Alcohol Consumption Decisions among Nonabusing Drinkers Diagnosed with Hepatitis
      C: An Exploratory Sequential Mixed Methods Study.
AB  - Most studies of decisions to curtail alcohol consumption reflect experiences of
      abusing drinkers. We employ an exploratory sequential research design to explore
      the applicability of this research to the experience of nonabusing drinkers
      advised to curtail alcohol consumption after a Hepatitis C diagnosis. A
      qualitative component identified 17 new decision factors not reflected in an
      inventory of factors based on synthesis of existing scales. We triangulated
      qualitative data by supplementing semi-structured interviews with Internet
      postings. A quantitative component estimated prevalence and association with
      current drinking of these new decision factors. Patients who quit drinking tended
      to attribute post-diagnosis drinking to occasional triggers, whereas patients who
      were still drinking were more likely to endorse rationales not tied to specific
      triggers.

PMID- 20046862
TI  - Interpretation in Social Anxiety: When Meaning Precedes Ambiguity.
AB  - Cognitive models of anxiety posit that negative beliefs influence socially
      anxious individuals' interpretation of ambiguous social cues. However, paradigms
      used to assess interpretation bias in social anxiety have not addressed such
      beliefs. Furthermore, studies have assessed interpretation with either self
      report or reaction time paradigms, rather than using both methods. In the current
      study, socially anxious and non-anxious participants completed the Word Sentence
      Association Paradigm (WSAP). In the WSAP, participants decide whether or not a
      word (implying a threat or benign interpretation) is related to an ambiguous
      sentence. Threat or benign meanings preceded the ambiguity in order to examine
      the influence of positive and negative beliefs on interpretation of ambiguous
      information. The WSAP results in two types of interpretation indices: (1)
      response latency to make relatedness decisions for threat and benign
      interpretations, and (2) endorsement rates of the relatedness of threat and
      benign interpretations to ambiguous sentences. Results revealed a threat
      interpretation bias and a lack of a benign interpretation bias in both reaction
      time and self-report data. Threat and benign biases were not strongly correlated.
      These findings support the distinction between threat and benign interpretation
      biases.

PMID- 20046860
TI  - Systems analysis of bone.
AB  - The genetic variants contributing to variability in skeletal traits has been well
      studied, and several hundred QTLs have been mapped and several genes contributing
      to trait variation have been identified. However, many questions remain
      unanswered. In particular, it is unclear whether variation in a single gene leads
      to alterations in function. Bone is a highly adaptive system and genetic variants
      affecting one trait are often accompanied by compensatory changes in other
      traits. The functional interactions among traits, which is known as phenotypic
      integration, has been observed in many biological systems, including bone.
      Phenotypic integration is a property of bone that is critically important for
      establishing a mechanically functional structure that is capable of supporting
      the forces imparted during daily activities. In this paper, bone is reviewed as a
      system and primarily in the context of functionality. A better understanding of
      the system properties of bone will lead to novel targets for future genetic
      analyses and the identification of genes that are directly responsible for
      regulating bone strength. This systems analysis has the added benefit of leaving
      a trail of valuable information about how the skeletal system works. This
      information will provide novel approaches to assessing skeletal health during
      growth and aging and for developing novel treatment strategies to reduce the
      morbidity and mortality associated with fragility fractures.

PMID- 20046863
TI  - Productive reduplication in a fundamentally monosyllabic language.
AB  - The question to be addressed in this paper is how a language which is
      fundamentally monosyllabic in structure can have about a dozen different
      reduplication types with at least eight different linguistic functions. The
      language under discussion, American Sign Language (ASL), is one representative of
      a class of languages that makes widespread use of reduplication for lexical and
      morphological purposes. The goal here is to present the set of phonological
      features that permit the productive construction of these forms and a first
      approximation to the feature geometry in which they participate. Reduplication
      forms are dependent on the event structure of the predicate and the associated
      aspectual modifications.

PMID- 20046864
TI  - Effects of sample handling and storage on quantitative lipid analysis in human
      serum.
AB  - There is sparse information about specific storage and handling protocols that
      minimize analytical error and variability in samples evaluated by targeted
      metabolomics. Variance components that affect quantitative lipid analysis in a
      set of human serum samples were determined. The effects of freeze-thaw,
      extraction state, storage temperature, and freeze-thaw prior to density-based
      lipoprotein fractionation were quantified. The quantification of high abundance
      metabolites, representing the biologically relevant lipid species in humans, was
      highly repeatable (with coefficients of variation as low as 0.01 and 0.02) and
      largely unaffected by 1-3 freeze-thaw cycles (with 0-8% of metabolites affected
      in each lipid class). Extraction state had effects on total lipid class amounts,
      including decreased diacylglycerol and increased phosphatidylethanolamine in
      thawed compared with frozen samples. The effects of storage temperature over 1
      week were minimal, with 0-4% of metabolites affected by storage at 4 degrees C, 
      20 degrees C, or -80 degrees C in most lipid classes, and 19% of metabolites in
      diacylglycerol affected by storage at -20 degrees C. Freezing prior to
      lipoprotein fractionation by density ultracentrifugation decreased HDL free
      cholesterol by 37% and VLDL free fatty acid by 36%, and increased LDL cholesterol
      ester by 35% compared with fresh samples. These findings suggest that density
      based fractionation should preferably be undertaken in fresh serum samples
      because up to 37% variability in HDL and LDL cholesterol could result from a
      single freeze-thaw cycle. Conversely, quantitative lipid analysis within
      unfractionated serum is minimally affected even with repeated freeze-thaw cycles.

PMID- 20046866
TI  - Constraint-based probabilistic learning of metabolic pathways from tomato
      volatiles.
AB  - Clustering and correlation analysis techniques have become popular tools for the
      analysis of data produced by metabolomics experiments. The results obtained from
      these approaches provide an overview of the interactions between objects of
      interest. Often in these experiments, one is more interested in information about
      the nature of these relationships, e.g., cause-effect relationships, than in the
      actual strength of the interactions. Finding such relationships is of crucial
      importance as most biological processes can only be understood in this way.
      Bayesian networks allow representation of these cause-effect relationships among
      variables of interest in terms of whether and how they influence each other given
      that a third, possibly empty, group of variables is known. This technique also
      allows the incorporation of prior knowledge as established from the literature or
      from biologists. The representation as a directed graph of these relationship is
      highly intuitive and helps to understand these processes. This paper describes
      how constraint-based Bayesian networks can be applied to metabolomics data and
      can be used to uncover the important pathways which play a significant role in
      the ripening of fresh tomatoes. We also show here how this methods of
      reconstructing pathways is intuitive and performs better than classical
      techniques. Methods for learning Bayesian network models are powerful tools for
      the analysis of data of the magnitude as generated by metabolomics experiments.
      It allows one to model cause-effect relationships and helps in understanding the
      underlying processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of
      this article (doi:10.1007/s11306-009-0166-2) contains supplementary material,
      which is available to authorized users.

PMID- 20046865
TI  - Mass-spectrometry-based metabolomics: limitations and recommendations for future
      progress with particular focus on nutrition research.
AB  - Mass spectrometry (MS) techniques, because of their sensitivity and selectivity,
      have become methods of choice to characterize the human metabolome and MS-based
      metabolomics is increasingly used to characterize the complex metabolic effects
      of nutrients or foods. However progress is still hampered by many unsolved
      problems and most notably the lack of well established and standardized methods
      or procedures, and the difficulties still met in the identification of the
      metabolites influenced by a given nutritional intervention. The purpose of this
      paper is to review the main obstacles limiting progress and to make
      recommendations to overcome them. Propositions are made to improve the mode of
      collection and preparation of biological samples, the coverage and quality of
      mass spectrometry analyses, the extraction and exploitation of the raw data, the
      identification of the metabolites and the biological interpretation of the
      results.

PMID- 20046867
TI  - Systems toxicology study of doxorubicin on rats using ultra performance liquid
      chromatography coupled with mass spectrometry based metabolomics.
AB  - A metabolomics-based systems toxicology approach was used to profile the urinary
      metabolites for the toxicity related processes and pathogenesis induced by
      doxorubicin (DOX) to rats. Endogenous metabolite profiles were obtained with
      ultra performance liquid chromatography-mass spectrometry (UPLC-MS) for rats
      receiving different single dosages of DOX (5, 10 or 20 mg/kg) prior and at three
      time points after dosage. Principal components analysis (PCA) allowed detection
      of two major systemic metabolic changes with the time due to the induced
      toxicity. Furthermore, Analysis of variance (ANOVA) Simultaneous Component
      Analysis (ASCA) was applied to reveal the variation caused by time and dose, and
      their interaction in a multivariate way. Finally, various metabolites involved in
      the toxic processes could be identified using their accurate mass and MS(n)
      experiments, and possible mechanisms of the toxicity of DOX were postulated. In
      conclusion, metabolomics as a systems toxicology approach was able to provide
      comprehensive information on the dynamic process of drug induced toxicity. In
      addition, detection of the systemic toxic effects could be obtained with
      metabolomics at an earlier stage compared to the clinical chemistry and
      histopathological assessment.

PMID- 20046868
TI  - Self-organized criticality theory of autoimmunity.
AB  - BACKGROUND: The cause of autoimmunity, which is unknown, is investigated from a
      different angle, i.e., the defect in immune 'system', to explain the cause of
      autoimmunity. METHODOLOGY/PRINCIPAL FINDINGS: Repeated immunization with antigen
      causes systemic autoimmunity in mice otherwise not prone to spontaneous
      autoimmune diseases. Overstimulation of CD4(+) T cells led to the development of
      autoantibody-inducing CD4(+) T (aiCD4(+) T) cell which had undergone T cell
      receptor (TCR) revision and was capable of inducing autoantibodies. The aiCD4(+)
      T cell was induced by de novo TCR revision but not by cross-reaction, and
      subsequently overstimulated CD8(+) T cells, driving them to become antigen
      specific cytotoxic T lymphocytes (CTL). These CTLs could be further matured by
      antigen cross-presentation, after which they caused autoimmune tissue injury akin
      to systemic lupus erythematosus (SLE). CONCLUSIONS/SIGNIFICANCE: Systemic
      autoimmunity appears to be the inevitable consequence of over-stimulating the
      host's immune 'system' by repeated immunization with antigen, to the levels that
      surpass system's self-organized criticality.

PMID- 20046869
TI  - Conditional inactivation of Brca1, p53 and Rb in mouse ovaries results in the
      development of leiomyosarcomas.
AB  - Epithelial ovarian cancer (EOC) is thought to arise in part from the ovarian
      surface epithelium (OSE); however, the molecular events underlying this
      transformation are poorly understood. Germline mutations in the BRCA1 tumor
      suppressor gene result in a significantly increased risk of developing EOC and a
      large proportion of sporadic EOCs display some sort of BRCA1 dysfunction. To
      generate a model in which Brca1-mediated transformation can be studied, we
      previously inactivated Brca1 alone in murine OSE, which resulted in an increased
      accumulation of premalignant changes, but no tumor formation. In this study, we
      examined tumor formation in mice with conditionally expressed alleles of Brca1,
      p53 and Rb, alone or in combination. Intrabursal injection of adenovirus
      expressing Cre recombinase to inactivate p53 resulted in tumors in 100% of mice.
      Tumor progression was accelerated in mice with concomitant inactivation of Brca1
      and p53, but not Rb and p53. Immunohistologic analyses classified the tumors as
      leiomyosarcomas that may be arising from the ovarian bursa. Brca1 inactivation in
      primary cultures of murine OSE cells led to a suppression of proliferation that
      could be rescued by concomitant inactivation of p53 and/or Rb. Brca1-deficient
      OSE cells displayed an increased sensitivity to the DNA damaging agent cisplatin,
      and this effect could be modulated by inactivation of p53 and/or Rb. These
      results indicate that Brca1 deficiency can accelerate tumor development and alter
      the sensitivity of OSE cells to chemotherapeutic agents. Intrabursal delivery of
      adenovirus intended to alter gene expression in the ovarian surface epithelium
      may, in some strains of mice, result in more rapid transformation of adjacent
      cells, resulting in leiomyosarcomas.

PMID- 20046870
TI  - Cellular levels of HIV unspliced RNA from patients on combination antiretroviral
      therapy with undetectable plasma viremia predict the therapy outcome.
AB  - BACKGROUND: Combination antiretroviral therapy (cART), the standard of care for
      HIV-1 infection, is considered to be successful when plasma viremia remains below
      the detection limit of commercial assays. Yet, cART fails in a substantial
      proportion of patients after the apparent success. No laboratory markers are
      known that are predictive of cART outcome in initial responders during the period
      of undetectable plasma viremia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report
      the results of a retrospective longitudinal study of twenty-six HIV-infected
      individuals who initially responded to cART by having plasma viremia suppressed
      to <50 copies/ml. Eleven of these patients remained virologically suppressed,
      whereas fifteen experienced subsequent cART failure. Using sensitive methods
      based on seminested real-time PCR, we measured the levels of HIV-1 proviral (pr)
      DNA, unspliced (us) RNA, and multiply spliced RNA in the peripheral blood
      mononuclear cells (PBMC) of these patients at multiple time points during the
      period of undetectable plasma viremia on cART. Median under-therapy level of
      usRNA was significantly higher (0.43 log(10) difference, P = 0.0015) in patients
      who experienced subsequent cART failure than in successfully treated patients. In
      multivariate analysis, adjusted for baseline CD4(+) counts, prior ART experience,
      and particular cART regimens, the maximal usRNA level under therapy was the best
      independent predictor of subsequent therapy failure (adjusted odds ratio [95%
      CI], 24.4 [1.5-389.5], P = 0.024). The only other factor significantly associated
      with cART failure was prior ART experience (adjusted odds ratio [95% CI], 12.3
      [1.1-138.4], P = 0.042). Levels of usRNA under cART inversely correlated with
      baseline CD4(+) counts (P = 0.0003), but did not correlate with either baseline
      usRNA levels or levels of prDNA under therapy. CONCLUSION: Our data demonstrate
      that the level of HIV-1 usRNA in PBMC, measured in cART-treated patients with
      undetectable plasma viremia, is a strong predictive marker for the outcome of
      therapy.

PMID- 20046871
TI  - Fgfr3 is a transcriptional target of Ap2delta and Ash2l-containing histone
      methyltransferase complexes.
AB  - Polycomb (PcG) and trithorax (trxG) proteins play important roles in establishing
      lineage-specific genetic programs through induction of chromatin modifications
      that lead to gene silencing or activation. Previously, we described an
      association between the MLL/SET1 complexes and a highly restricted, gene-specific
      DNA-binding protein Ap2delta that is required for recruitment of the MLL/SET1
      complex to target Hoxc8 specifically. Here, we reduced levels of Ap2delta and
      Ash2l in the neuroblastoma cell line, Neuro2A, and analyzed their gene expression
      profiles using whole-genome mouse cDNA microarrays. This analysis yielded 42
      genes that are potentially co-regulated by Ap2delta and Ash2l, and we have
      identified evolutionarily conserved Ap2-binding sites in 20 of them. To determine
      whether some of these were direct targets of the Ap2delta-Ash2l complex, we
      analyzed several promoters for the presence of Ap2delta and Ash2l by chromatin
      immunoprecipitation (ChIP). Among the targets we screened, we identified Fgfr3 as
      a direct transcriptional target of the Ap2delta-Ash2l complex. Additionally, we
      found that Ap2delta is necessary for the recruitment of Ash2l-containing
      complexes to this promoter and that this recruitment leads to trimethylation of
      lysine 4 of histone H3 (H3K4me3). Thus, we have identified several candidate
      targets of complexes containing Ap2delta and Ash2l that can be used to further
      elucidate their roles during development and showed that Fgfr3 is a novel direct
      target of these complexes.

PMID- 20046872
TI  - Derivation of a triple mosaic adenovirus for cancer gene therapy.
AB  - A safe and efficacious cancer medicine is necessary due to the increasing
      population of cancer patients whose particular diseases cannot be cured by the
      currently available treatment. Adenoviral (Ad) vectors represent a promising
      therapeutic medicine for human cancer therapy. However, several improvements are
      needed in order for Ad vectors to be effective cancer therapeutics, which
      include, but are not limited to, improvement of cellular uptake, enhanced cancer
      cell killing activity, and the capability of vector visualization and tracking
      once injected into the patients. To this end, we attempted to develop an Ad as a
      multifunctional platform incorporating targeting, imaging, and therapeutic
      motifs. In this study, we explored the utility of this proposed platform by
      generating an Ad vector containing the poly-lysine (pK), the herpes simplex virus
      type 1 (HSV-1) thymidine kinase (TK), and the monomeric red fluorescent protein
      (mRFP1) as targeting, tumor cell killing, and imaging motifs, respectively. Our
      study herein demonstrates the generation of the triple mosaic Ad vector with pK,
      HSV-1 TK, and mRFP1 at the carboxyl termini of Ad minor capsid protein IX (pIX).
      In addition, the functionalities of pK, HSV-1 TK, and mRFP1 proteins on the Ad
      vector were retained as confirmed by corresponding functional assays, indicating
      the potential multifunctional application of this new Ad vector for cancer gene
      therapy. The validation of the triple mosaic Ad vectors also argues for the
      ability of pIX modification as a base for the development of multifunctional Ad
      vectors.

PMID- 20046873
TI  - Streptococcus pneumoniae coinfection is correlated with the severity of H1N1
      pandemic influenza.
AB  - BACKGROUND: Initial reports in May 2009 of the novel influenza strain H1N1pdm
      estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal
      influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths,
      representing a CFR of 4.5%. Potential explanations for increased CFR included
      virus reassortment or genetic drift, or infection of a more vulnerable
      population. Virus genomic sequencing of 26 Argentinian samples representing both
      severe and mild disease indicated no evidence of reassortment, mutations
      associated with resistance to antiviral drugs, or genetic drift that might
      contribute to virulence. Furthermore, no evidence was found for increased
      frequency of risk factors for H1N1pdm disease. METHODS/PRINCIPAL FINDINGS: We
      examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection
      from Argentina with MassTag PCR, testing for 33 additional microbial agents. The
      study population consisted of 199 H1N1pdm-infected subjects sampled between 23
      June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or
      hospitalization (n = 19); 160 had mild disease. At least one additional agent of
      potential pathogenic importance was identified in 152 samples (76%), including
      Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human
      respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1)
      and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella
      pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1);
      and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n =
      6). The presence of S. pneumoniae was strongly correlated with severe disease. S.
      pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more
      than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe
      disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55
      years of age, the adjusted odds ratio (OR) of severe disease in the presence of
      S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001).
      CONCLUSIONS/SIGNIFICANCE: The association of S. pneumoniae with morbidity and
      mortality is established in the current and previous influenza pandemics.
      However, this study is the first to demonstrate the prognostic significance of
      non-invasive antemortem diagnosis of S. pneumoniae infection and may provide
      insights into clinical management.

PMID- 20046875
TI  - Histidine-rich glycoprotein can prevent development of mouse experimental
      glioblastoma.
AB  - Extensive angiogenesis, formation of new capillaries from pre-existing blood
      vessels, is an important feature of malignant glioma. Several antiangiogenic
      drugs targeting vascular endothelial growth factor (VEGF) or its receptors are
      currently in clinical trials as therapy for high-grade glioma and bevacizumab was
      recently approved by the FDA for treatment of recurrent glioblastoma. However,
      the modest efficacy of these drugs and emerging problems with anti-VEGF treatment
      resistance welcome the development of alternative antiangiogenic therapies. One
      potential candidate is histidine-rich glycoprotein (HRG), a plasma protein with
      antiangiogenic properties that can inhibit endothelial cell adhesion and
      migration. We have used the RCAS/TV-A mouse model for gliomas to investigate the
      effect of HRG on brain tumor development. Tumors were induced with platelet
      derived growth factor-B (PDGF-B), in the presence or absence of HRG. We found
      that HRG had little effect on tumor incidence but could significantly inhibit the
      development of malignant glioma and completely prevent the occurrence of grade IV
      tumors (glioblastoma).

PMID- 20046876
TI  - Subnanomolar Detection Limit Application of Ion-Selective Electrodes with Three
      Dimensionally Ordered Macroporous (3DOM) Carbon Solid Contacts.
AB  - Solid-contact ion-selective electrodes (SC-ISEs) can exhibit very low detection
      limits and, in contrast to conventional ISEs, do not require an optimization of
      the inner filling solution. This work shows that subnanomolar detection limits
      can also be achieved with SC-ISEs with three-dimensionally ordered macroporous
      (3DOM) carbon contacts, which have been shown recently to exhibit excellent long
      term stabilities and good resistance to the interferences from oxygen and light.
      The detection limit of 3DOM carbon-contacted electrodes with plasticized
      poly(vinyl chloride) as membrane matrix can be improved with a high polymer
      content of the sensing membrane, a large ratio of ionophore and ionic sites, and
      conditioning with a low concentration of analyte ions. This permits detection
      limits as low as 1.6*10(-7) M for K(+) and 4.0*10(-11) M for Ag(+).

PMID- 20046874
TI  - A disease model for wheezing disorders in preschool children based on clinicians'
      perceptions.
AB  - BACKGROUND: Wheezing disorders in childhood vary widely in clinical presentation
      and disease course. During the last years, several ways to classify wheezing
      children into different disease phenotypes have been proposed and are
      increasingly used for clinical guidance, but validation of these hypothetical
      entities is difficult. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was
      to develop a testable disease model which reflects the full spectrum of wheezing
      illness in preschool children. We performed a qualitative study among a panel of
      7 experienced clinicians from 4 European countries working in primary, secondary
      and tertiary paediatric care. In a series of questionnaire surveys and structured
      discussions, we found a general consensus that preschool wheezing disorders
      consist of several phenotypes, with a great heterogeneity of specific disease
      concepts between clinicians. Initially, 24 disease entities were described among
      the 7 physicians. In structured discussions, these could be narrowed down to
      three entities which were linked to proposed mechanisms: a) allergic wheeze, b)
      non-allergic wheeze due to structural airway narrowing and c) non-allergic wheeze
      due to increased immune response to viral infections. This disease model will
      serve to create an artificial dataset that allows the validation of data-driven
      multidimensional methods, such as cluster analysis, which have been proposed for
      identification of wheezing phenotypes in children. CONCLUSIONS/SIGNIFICANCE:
      While there appears to be wide agreement among clinicians that wheezing disorders
      consist of several diseases, there is less agreement regarding their number and
      nature. A great diversity of disease concepts exist but a unified phenotype
      classification reflecting underlying disease mechanisms is lacking. We propose a
      disease model which may help guide future research so that proposed mechanisms
      are measured at the right time and their role in disease heterogeneity can be
      studied.

PMID- 20046877
TI  - Monoamine oxidase A gene (MAOA) associated with attitude towards longshot risks.
AB  - Decision making often entails longshot risks involving a small chance of
      receiving a substantial outcome. People tend to be risk preferring (averse) when
      facing longshot risks involving significant gains (losses). This differentiation
      towards longshot risks underpins the markets for lottery as well as for
      insurance. Both lottery and insurance have emerged since ancient times and
      continue to play a useful role in the modern economy. In this study, we observe
      subjects' incentivized choices in a controlled laboratory setting, and
      investigate their association with a widely studied, promoter-region repeat
      functional polymorphism in monoamine oxidase A gene (MAOA). We find that subjects
      with the high activity (4-repeat) allele are characterized by a preference for
      the longshot lottery and also less insurance purchasing than subjects with the
      low activity (3-repeat) allele. This is the first result to link attitude towards
      longshot risks to a specific gene. It complements recent findings on the
      neurobiological basis of economic risk taking.

PMID- 20046878
TI  - Functional and transcriptional characterization of human embryonic stem cell
      derived endothelial cells for treatment of myocardial infarction.
AB  - BACKGROUND: Differentiation of human embryonic stem cells into endothelial cells
      (hESC-ECs) has the potential to provide an unlimited source of cells for novel
      transplantation therapies of ischemic diseases by supporting angiogenesis and
      vasculogenesis. However, the endothelial differentiation efficiency of the
      conventional embryoid body (EB) method is low while the 2-dimensional method of
      co-culturing with mouse embryonic fibroblasts (MEFs) require animal product, both
      of which can limit the future clinical application of hESC-ECs. Moreover, to
      fully understand the beneficial effects of stem cell therapy, investigators must
      be able to track the functional biology and physiology of transplanted cells in
      living subjects over time. METHODOLOGY: In this study, we developed an
      extracellular matrix (ECM) culture system for increasing endothelial
      differentiation and free from contaminating animal cells. We investigated the
      transcriptional changes that occur during endothelial differentiation of hESCs
      using whole genome microarray, and compared to human umbilical vein endothelial
      cells (HUVECs). We also showed functional vascular formation by hESC-ECs in a
      mouse dorsal window model. Moreover, our study is the first so far to transplant
      hESC-ECs in a myocardial infarction model and monitor cell fate using molecular
      imaging methods. CONCLUSION: Taken together, we report a more efficient method
      for derivation of hESC-ECs that express appropriate patterns of endothelial
      genes, form functional vessels in vivo, and improve cardiac function. These
      studies suggest that hESC-ECs may provide a novel therapy for ischemic heart
      disease in the future.

PMID- 20046880
TI  - SNAI1 and SNAI2 are asymmetrically expressed at the 2-cell stage and become
      segregated to the TE in the mouse blastocyst.
AB  - SNAI1 and SNAI2 are transcription factors that initiate Epithelial-to-Mesenchymal
      cell transitions throughout development and in cancer metastasis. Here we show
      novel expression of SNAI1 and SNAI2 throughout mouse preimplantation development
      revealing asymmetrical localization of both SNAI1 and SNAI2 in individual
      blastomeres beginning at the 2-cell stage through to the 8-cell stage where SNAI1
      and SNAI2 are then only detected in outer cells and not inner cells of the
      blastocyst. This study implicates SNAI1 and SNAI2 in the lineage segregation of
      the trophectoderm and inner cell mass, and provides new insight into these
      oncogenes.

PMID- 20046879
TI  - Induction of ovarian leiomyosarcomas in mice by conditional inactivation of Brca1
      and p53.
AB  - BACKGROUND: Approximately one out of every ten cases of epithelial ovarian cancer
      (EOC) is inherited. The majority of inherited cases of EOC result from mutations
      in the breast cancer associated gene 1 (BRCA1). In addition to mutation of BRCA1,
      mutation of the p53 gene is often found in patients with inherited breast and
      ovarian cancer syndrome. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role
      of loss of function of BRCA1 and p53 in ovarian cancer development using mouse
      models with conditionally expressed alleles of Brca1 and/or p53. Our results show
      that ovary-specific Cre-recombinase-mediated conditional inactivation of both
      Brca1(LoxP/LoxP) and p53(LoxP/LoxP) resulted in ovarian or reproductive tract
      tumor formation in 54% of mice, whereas conditional inactivation of either allele
      alone infrequently resulted in tumors (< or =5% of mice). In mice with
      conditionally inactivated Brca1(LoxP/LoxP) and p53(LoxP/LoxP), ovarian tumors
      arose after long latency with the majority exhibiting histological features
      consistent with high grade leiomyosarcomas lacking expression of epithelial,
      follicular or lymphocyte markers. In addition, tumors with conditional
      inactivation of both Brca1(LoxP/LoxP) and p53(LoxP/LoxP) exhibited greater
      genomic instability compared to an ovarian tumor with inactivation of only
      p53(LoxP/LoxP). CONCLUSIONS/SIGNIFICANCE: Although conditional inactivation of
      both Brca1 and p53 results in ovarian tumorigenesis, our results suggest that
      additional genetic alterations or alternative methods for targeting epithelial
      cells of the ovary or fallopian tube for conditional inactivation of Brca1 and
      p53 are required for the development of a mouse model of Brca1-associated
      inherited EOC.

PMID- 20046881
TI  - Exploring hypotheses of the actions of TGF-beta1 in epidermal wound healing using
      a 3D computational multiscale model of the human epidermis.
AB  - In vivo and in vitro studies give a paradoxical picture of the actions of the key
      regulatory factor TGF-beta1 in epidermal wound healing with it stimulating
      migration of keratinocytes but also inhibiting their proliferation. To try to
      reconcile these into an easily visualized 3D model of wound healing amenable for
      experimentation by cell biologists, a multiscale model of the formation of a 3D
      skin epithelium was established with TGF-beta1 literature-derived rule sets and
      equations embedded within it. At the cellular level, an agent-based bottom-up
      model that focuses on individual interacting units (keratinocytes) was used. This
      was based on literature-derived rules governing keratinocyte behavior and
      keratinocyte/ECM interactions. The selection of these rule sets is described in
      detail in this paper. The agent-based model was then linked with a subcellular
      model of TGF-beta1 production and its action on keratinocytes simulated with a
      complex pathway simulator. This multiscale model can be run at a cellular level
      only or at a combined cellular/subcellular level. It was then initially
      challenged (by wounding) to investigate the behavior of keratinocytes in wound
      healing at the cellular level. To investigate the possible actions of TGF-beta1,
      several hypotheses were then explored by deliberately manipulating some of these
      rule sets at subcellular levels. This exercise readily eliminated some hypotheses
      and identified a sequence of spatial-temporal actions of TGF-beta1 for normal
      successful wound healing in an easy-to-follow 3D model. We suggest this
      multiscale model offers a valuable, easy-to-visualize aid to our understanding of
      the actions of this key regulator in wound healing, and provides a model that can
      now be used to explore pathologies of wound healing.

PMID- 20046882
TI  - Diverse hematological malignancies including hodgkin-like lymphomas develop in
      chimeric MHC class II transgenic mice.
AB  - A chimeric HLA-DR4-H2-E (DR4) homozygous transgenic mouse line spontaneously
      develops diverse hematological malignancies with high frequency (70%). The
      majority of malignancies were distributed equally between T and B cell neoplasms
      and included lymphoblastic T cell lymphoma (LTCL), lymphoblastic B cell lymphoma
      (LBCL), diffuse large B cell lymphoma (DLBCL), the histiocyte/T cell rich variant
      of DLBCL (DLBCL-HA/T cell rich DLBCL), splenic marginal zone lymphoma (SMZL),
      follicular B cell lymphoma (FBL) and plasmacytoma (PCT). Most of these neoplasms
      were highly similar to human diseases. Also, some non-lymphoid malignancies such
      as acute myeloid leukemia (AML) and histiocytic sarcoma were found.
      Interestingly, composite lymphomas, including Hodgkin-like lymphomas, were also
      detected that had CD30(+) Hodgkin/Reed-Sternberg (H/RS)-like cells, representing
      a tumor type not previously described in mice. Analysis of microdissected H/RS
      like cells revealed their origin as germinal center B cells bearing somatic
      hypermutations and, in some instances, crippled mutations, as described for human
      Hodgkin lymphoma (HL). Transgene integration in an oncogene was excluded as an
      exclusive driving force of tumorigenesis and age-related lymphoma development
      suggests a multi-step process. Thus, this DR4 line is a useful model to
      investigate common molecular mechanisms that may contribute to important
      neoplastic diseases in man.

PMID- 20046883
TI  - Bone marrow transplantation results in human donor blood cells acquiring and
      displaying mouse recipient class I MHC and CD45 antigens on their surface.
AB  - BACKGROUND: Mouse models of human disease are invaluable for determining the
      differentiation ability and functional capacity of stem cells. The best example
      is bone marrow transplants for studies of hematopoietic stem cells. For organ
      studies, the interpretation of the data can be difficult as transdifferentiation,
      cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as
      differentiation. These events have not been investigated in hematopoietic stem
      cell transplant models. METHODOLOGY/PRINCIPAL FINDINGS: In this study we
      investigated fusion and trogocytosis involving blood cells during bone marrow
      transplantation using a xenograft model. We report that using a standard SCID
      repopulating assay almost 100% of the human donor cells appear as hybrid blood
      cells containing both mouse and human surface antigens. CONCLUSION/SIGNIFICANCE:
      Hybrid cells are not the result of cell-cell fusion events but appear to be due
      to efficient surface antigen transfer, a process referred to as trogocytosis.
      Antigen transfer appears to be non-random and includes all donor cells regardless
      of sub-type. We also demonstrate that irradiation preconditioning enhances the
      frequency of hybrid cells and that trogocytosis is evident in non-blood cells in
      chimera mice.

PMID- 20046884
TI  - Clinical Perspective and Recent Development of PET Radioligands for Imaging
      Cerebral Nicotinic Acetylcholine Receptors.

PMID- 20046885
TI  - A Survey of Statistical Models for Reverse Engineering Gene Regulatory Networks.
AB  - Statistical models for reverse engineering gene regulatory networks are surveyed
      in this article. To provide readers with a system-level view of the modeling
      issues in this research, a graphical modeling framework is proposed. This
      framework serves as the scaffolding on which the review of different models can
      be systematically assembled. Based on the framework, we review many existing
      models for many aspects of gene regulation; the pros and cons of each model are
      discussed. In addition, network inference algorithms are also surveyed under the
      graphical modeling framework by the categories of point solutions and
      probabilistic solutions and the connections and differences among the algorithms
      are provided. This survey has the potential to elucidate the development and
      future of reverse engineering GRNs and bring statistical signal processing closer
      to the core of this research.

PMID- 20046886
TI  - Mind-Body Solutions for Obesity.

PMID- 20046888
TI  - Absorption, Conjugation and Efflux of the Flavonoids, Kaempferol and Galangin,
      Using the Intestinal CACO-2/TC7 Cell Model.
AB  - Flavonoids are biologically active compounds in food with potential health
      effects. We have used the Caco-2 cell monolayer model to study the absorption and
      metabolism of two flavonols, a class of flavonoids, specifically kaempferol and
      galangin. Metabolism experiments allowed identification of 5 kaempferol
      conjugates: 3-, 7- and 4'-glucuronide, a sulphate and a glucurono-sulphate; and 4
      galangin conjugates: 3-, 5- and 7-glucuronides, and a sulphate, using specific
      enzyme hydrolysis, HPLC-MS, and HPLC with post column metal complexation/tandem
      MS. Transport studies showed that the flavonols were conjugated inside the cells
      then transported across the monolayer or effluxed back to the apical side.
      Sulphated conjugates were preferentially effluxed back to the apical side,
      whereas glucuronides were mostly transported to the basolateral side. For
      kaempferol, a small amount of the unconjugated aglycone permeated in both
      directions, indicating some passive diffusion. When kaempferol-3-glucuronide and
      quercetin7-sulphate were applied to either side of the cells, no permeation in
      either direction was observed, indicating that conjugates cannot re-cross the
      cell monolayer. Formation of apical kaempferol-7- and 4'-glucuronides was readily
      saturated, whereas formation of other conjugates at the apical side and all at
      the basolateral side increased with increasing concentration of kaempferol,
      implying different transporters are responsible at the apical and basolateral
      sides. The results highlight the important but complex metabolic changes
      occurring in flavonoids during absorption.

PMID- 20046887
TI  - Discovery of anticancer agents of diverse natural origin.
AB  - A collaborative multidisciplinary research project is described in which new
      natural product anticancer drug leads are obtained from a diverse group of
      organisms, constituted by tropical plants, aquatic cyanobacteria, and filamentous
      fungi. Information is provided on how these organisms are collected and
      processed. The types of bioassays are indicated in which crude extracts of these
      acquisitions are tested. Progress made in the isolation of lead bioactive
      secondary metabolites from three tropical plants is discussed.

PMID- 20046889
TI  - Formation of Mitochondrial Genome Concatemers as an Alternative Mechanism
      Promoting Oncogenic Transformation of Lymphoid Cells.
AB  - We have previously shown that AIDS-associated lymphomas and lymphoma cell lines
      contain mitochondrial genome concatemers not present in normal T-lymphocytes.
      Since cellular homeostasis and energy production rely heavily on mitochondrial
      DNA (mtDNA) stability, mutations in the mtDNA have long been linked to the
      development of various types of cancers. In most of the cases, however,
      neoplastically transformed cells harbor non-mutated mtDNA. Herein, we propose an
      alternative mechanism that shows how the formation of mitochondrial genome
      concatemers may promote oncogenic transformation of normal lymphoid progenitor
      cells when no mtDNA mutations or chromosomal aberrations are present. We detected
      high reactive oxygen species (ROS) levels in the lymphoma samples tested despite
      no identification of putative mutations in the coding mtDNA. We propose that the
      formation of atypical mtDNA configurations (i.e. dimers and concatemers)
      interferes with normal mitochondrial function. Unstable mitochondria lead to
      abnormal assembly and dysfunction of the oxidative phosphorylation (OXPHOS)
      complexes, eventually leading to oxidative stress from elevated production of
      intracellular ROS. ROS have been reported to activate transcription factors
      associated with cellular proliferation and apoptosis inhibition. Therefore, we
      hypothesize that formation of mitochondrial genome concatemers can augment
      endogenous ROS levels capable of promoting oncogenic transformation of normal
      lymphoid progenitor cells.

PMID- 20046890
TI  - Magneto-Hydrodynamics Based Microfluidics.
AB  - In microfluidic devices, it is necessary to propel samples and reagents from one
      part of the device to another, stir fluids, and detect the presence of chemical
      and biological targets. Given the small size of these devices, the above tasks
      are far from trivial. Magnetohydrodynamics (MHD) offers an elegant means to
      control fluid flow in microdevices without a need for mechanical components. In
      this paper, we review the theory of MHD for low conductivity fluids and describe
      various applications of MHD such as fluid pumping, flow control in fluidic
      networks, fluid stirring and mixing, circular liquid chromatography, thermal
      reactors, and microcoolers.

PMID- 20046892
TI  - Timing effects of syllable structure and stress on nasals: a real-time MRI
      examination.
AB  - The coordination of velum and oral gestures for English [n] is studied using real
      time MRI movies to reconstruct vocal tract aperture functions. This technique
      allows for the examination of parts of the vocal tract otherwise inaccessible to
      dynamic imaging or movement tracking. The present experiment considers syllable
      onset, coda, and juncture geminate nasals and also addresses the effects of a
      variety of word stress patterns on segment internal coordination. We find a
      bimodal timing pattern in which near-synchrony of velum lowering and tongue tip
      raising characterizes the timing for onsets and temporal lag between the gestures
      is characteristic for codas, supporting and extending the findings of Krakow
      (1989), 1993) for [m]. Intervocalic word-internal nasals are found to have timing
      patterns that are sensitive to the local stress context, which suggests the
      presence of an underlying timing specification that can yield flexibly. We
      consider these findings in light of the gestural coupling structures described by
      Goldstein and colleagues (Goldstein, Byrd, & Saltzman 2006; Nam, Goldstein, and
      Saltzman in press; Goldstein, Nam, Saltzman, & Chitoran 2008).

PMID- 20046891
TI  - PET Radiotracers for Imaging the Proliferative Status of Solid Tumors.
AB  - Two different strategies have been developed for imaging the proliferative status
      of solid tumors with the functional imaging technique, Positron Emission
      Tomography (PET). The first strategy uses carbon-11 labeled thymidine and/or,
      more recently, fluorine-18 labeled thymidine analogs. These agents are a
      substrate for the enzyme thymidine kinase-1 (TK-1) and provide a pulse label of
      the number of cells in S phase. The second method for imaging the proliferative
      status of a tumor uses radiolabeled ligands that bind to the sigma-2 receptor
      which has a 10-fold higher density in proliferating (P) tumor cells versus
      quiescent (Q) tumor cells. This article compares and contrasts the two different
      strategies for imaging the proliferative status of solid tumors, and describes
      the strengths and weaknesses of each approach. 

PMID- 20046893
TI  - A Scalable Framework For Segmenting Magnetic Resonance Images.
AB  - A fast, accurate and fully automatic method of segmenting magnetic resonance
      images of the human brain is introduced. The approach scales well allowing fast
      segmentations of fine resolution images. The approach is based on modifications
      of the soft clustering algorithm, fuzzy c-means, that enable it to scale to large
      data sets. Two types of modifications to create incremental versions of fuzzy c
      means are discussed. They are much faster when compared to fuzzy c-means for
      medium to extremely large data sets because they work on successive subsets of
      the data. They are comparable in quality to application of fuzzy c-means to all
      of the data. The clustering algorithms coupled with inhomogeneity correction and
      smoothing are used to create a framework for automatically segmenting magnetic
      resonance images of the human brain. The framework is applied to a set of normal
      human brain volumes acquired from different magnetic resonance scanners using
      different head coils, acquisition parameters and field strengths. Results are
      compared to those from two widely used magnetic resonance image segmentation
      programs, Statistical Parametric Mapping and the FMRIB Software Library (FSL).
      The results are comparable to FSL while providing significant speed-up and better
      scalability to larger volumes of data.

PMID- 20046895
TI  - Simultaneous Quantification of Anandamide and Other Endocannabinoids in Dorsal
      Vagal Complex of Rat Brainstem by LC-MS.
AB  - A quantitative method has been developed and validated for the simultaneous
      determination of anandamide (AEA), docosatetraenylethanolamide (DEA) and N
      arachidonyldopamine (NADA) in dorsal vagal complex (DVC) of rat brainstem by
      liquid chromatographic-electrospray ionization mass spectrometry. The analytes
      were extracted from the tissue samples of rat brainstem by a single step liquid
      extraction technique using acetonitrile. The chromatographic separation was
      conducted on a C18 column using a gradient mobile phase consisting of methanol
      and water at a flow rate of 0.3 mL min(-1). The analytes were quantified by
      positive electrospray ionization mass spectrometry with selected ion monitoring
      (SIM) mode. The limits of detection (LOD) for AEA, DEA and NADA were 0.5, 1 and
      0.5 ng mL(-1), respectively. This method required only simple processing of the
      samples and could be applied to monitor the change in the level of these
      compounds in DVC of the rat brain tissue. Time dependent (10-70 min) accumulation
      of the endocannabinoids (AEA, DEA, and NADA) in brain tissue was also studied,
      which included a novel examination of the accumulation of DEA as a function of
      time in rat brain tissue after decapitation.

PMID- 20046896
TI  - PREPARATIVE SEPARATION OF AXIFOLIN-3-GLUCOSIDE, HYPEROSIDE AND AMYGDALIN FROM
      PLANT EXTRACTS BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY.
AB  - High-speed countercurrent chromatography (HSCCC) was successfully used to isolate
      three bioactive compounds, i.e., amygdalin from bitter almond and taxifolin-3
      glucoside and quercetin-3-galactoside (hyperoside) from water extract of
      Agrimonia pilosa Ledeb, respectively. From 1 g of the crude extract 65 mg of
      amygdalin was isolated at 97% purity using a two-phase solvent system composed of
      ethyl acetate-n-butanol-water (5:2:5, v/v) by preparative HSCCC. From a 400 mg
      amount of crude extract of Agrimonia pilosa Ledeb, 11 mg of taxifolin-3-glucoside
      and 8 mg of hyperoside were isolated at 96% purity using a two-phase solvent
      system composed of ethyl acetate-methanol-water (25:1:25, v/v) similarly by
      preparative HSCCC. The final structural identification was performed by MS, (1)H
      NMR and (13)C-NMR Spectra.

PMID- 20046894
TI  - Moderate expression of TRF2 in the hematopoietic system increases development of
      large cell blastic T-cell lymphomas.
AB  - The telomeric repeat binding factor 2 (TRF2) plays a central role in the
      protection of chromosome ends by inhibiting telomeres from initiating a DNA
      damage cascade. TRF2 overexpression has been suggested to induce tumor
      development in the mouse, and TRF2 levels have been found increased in human
      tumors. Here we tested whether moderate expression of TRF2 in the hematopoietic
      system leads to cancer development in the mouse. TRF2 and a GFP-TRF2 fusion
      protein were introduced into hematopoietic precursors, and tested for function.
      TRF2 overexpressing cells were integrated into the hematopoietic system of
      C57BL/6J recipient mice, and animals were put on tumor watch. An increase in the
      development of T-cell lymphomas was observed in secondary recipient animals,
      however, overexpression of the TRF2 transgene was not detectable anymore in the
      tumors. The tumors were characterized as large cell blastic T-cell lymphomas and
      displayed signs of genome instability as evidenced by chromosome fusions.
      However, the rate of lymphoma development in TRF2-overexpressing animals was low,
      suggesting the TRF2 does not serve as a dominant oncogene in the system used.

PMID- 20046897
TI  - Cell Separation by Non-Inertial Force Fields in Microfluidic Systems.
AB  - Cell and microparticle separation in microfluidic systems has recently gained
      significant attention in sample preparations for biological and chemical studies.
      Microfluidic separation is typically achieved by applying differential forces on
      the target particles to guide them into different paths. This paper reviews basic
      concepts and novel designs of such microfluidic separators with emphasis on the
      use of non-inertial force fields, including dielectrophoretic force, optical
      gradient force, magnetic force, and acoustic primary radiation force. Comparisons
      of separation performances with discussions on physiological effects and
      instrumentation issues toward point-of-care devices are provided as references
      for choosing appropriate separation methods for various applications.

PMID- 20046898
TI  - Physiological Profiles During Delay of Gratification: Associations with
      Emotionality, Self-regulation, and Adjustment Problems.
AB  - This longitudinal study utilized a community sample of children (N=91, 45%
      female, 8-11 years at time 1) to investigate physiological responses (heart rate
      reactivity [HRR] and electrodermal responding [EDR]) during delay of
      gratification in relation to emotionality, self-regulation, and adjustment
      problems. Cluster analyses identified three profiles among children who
      successfully delayed: children who waited easily with low EDR and moderate HRR,
      children who had difficulty waiting with high EDR and moderate HRR, and children
      who had difficulty waiting with low EDR and low HRR. The 3 clusters and children
      who did not wait were compared. Children with low EDR-low HRR had the lowest self
      regulation, and like the no-wait group, demonstrated the greatest baseline
      adjustment problems. The high EDR-moderate HRR group demonstrated highest self
      regulation and increases in depression across one year. Distinct profiles among
      children in delay contexts point to children who are over- and under-regulated
      with implications for adjustment problems.

PMID- 20046899
TI  - Microbubble Generation in Phase-Shift Nanoemulsions used as Anticancer Drug
      Carriers.
AB  - The paper describes droplet-to-bubble transition in block copolymer stabilized
      perfluoropentane nanoemulsions. Three physical factors that trigger droplet-to
      bubble transition in liquid emulsions and gels were evaluated, namely heat,
      ultrasound, and injections through fine-gauge needles. Among those listed,
      ultrasound irradiation was found the most efficient factor. Possible mechanisms
      of bubble generation and growth discussed in the paper include liquid-to-gas
      transition inside the individual bubble; bubble coalescence; and diffusion of
      dissolved air and/or perfluoropentane from small bubbles into larger bubbles
      (i.e., Oswald ripening). The last two factors result in irreversibility of the
      droplet-to-bubble transition. In gel matrices, ultrasound-induced droplet-to
      bubble transition was substantially inhibited but was catalyzed by large (hundred
      micron) pre-existing bubbles irradiated by low frequency (hundred kilohertz)
      ultrasound. The dependence of the droplet-to-bubble transition on initial bubble
      size is theoretically treated and the role of increase of surface area in
      promoting bubble coalescence is discussed. Therapeutic implications of observed
      effects are discussed.

PMID- 20046900
TI  - Comparative Study on Separation and Purification of Isoflavones from the Seeds
      and Sprouts of Chickpea by HSCCC.
AB  - Chickpea is known as a plant that is rich in protein, carbohydrates, and
      nutrition, and its seeds and sprouts have been processed into various health
      foods. In the present study, four isoflavones were purified from the seeds and
      sprouts of chickpea by high speed countercurrent chromatography (HSCCC) using two
      biphasic solvent systems composed of n-hexane-ethyl acetate-methanol-water
      (5:5:5:5, v/v) and ethyl acetate-water (1:1 v/v). The results indicated that 14.2
      mg of formononetin, 15.7 mg of biochanin A, 9.1 mg of ononin, 11.3 mg of
      biochanin A-7-O-beta-D-glucoside were obtained from 150 mg of sprout extracts
      with the purity of 92.26%, 95.86%, 95.32%, and 96.56%, respectively. Compared
      with the sprouts, separation of seed extracts yielded less amounts of biochanin A
      7-O-beta-D-glucoside and biochanin A with lower purity. The results indicate that
      four main isoflavones in chickpea, i.e., isoflavones, formononetin, biochanin A,
      ononin, and biochanin A-7-O-beta-D-glucoside, are substantially increased by
      biosynthesis during the seed germination.

PMID- 20046901
TI  - Invariance, or Noninvariance: That Is the Question.
AB  - Nesselroade et al. developed a new, interesting way to enforce invariance at the
      second-order level in P-technique models, while letting first-order structure to
      stray from invariance. We discuss our concerns with this approach under the
      headings of falsifiability, the nature of manifest variables included in models,
      and differential emphasis on generators of behavior versus output behavior. We
      supply a modified idiographic model for P-technique analyses and discuss the
      utility of this new approach in comparison to the Nesselroade et al. procedure.

PMID- 20046902
TI  - Screening of Uruguayan plants for deterrent activity against insects.
AB  - We evaluated the anti-insectan activity of extracts from different vegetative
      parts of ten plant species native to Uruguay. The selected plants belong to five
      families: Bignoniaceae: Clytostoma callistegioides, Dolichandra cynanchoides,
      Macfadyena unguis-cati; Sapindaceae: Dodonaea viscosa, Allophylus edulis,
      Serjania meridionalis; Lamiaceae: Salvia procurrens, Salvia guaranitica;
      Solanaceae: Lycium cestroides; and Phytolaccaceae: Phytolacca dioica. The
      extracts were evaluated in independent bioassays against four insect pests and
      one beneficial insect. Aphid settling inhibition was evaluated with a grass
      specialist, Rhopalosiphum padi, and a feeding generalist, Myzus persicae (both
      Hemiptera: Aphididae). Antifeedant activity was tested with adults of the
      specialist Epilachna paenulata (Coleoptera: Coccinellidae) and larvae of the
      generalist Spodoptera littoralis (Lepidoptera: Noctuidae). Finally, contact
      toxicity was assessed with honey bees, Apis mellifera (Hymenoptera: Apidae).
      Strong settling inhibition (SI) activity (expressed as %SI, where 100% means
      complete inhibition by the extract) was found only for the twig extracts of A.
      edulis (Sapindaceae) against M. persicae (% SI = 77 +/- 4). Antifeedant activity
      (expressed as % of feeding reduction (FR), where 100% means no consumption on
      extract-treated diet) against E. paenulata was significant for the leaf extracts
      of L. cestroides (Solanaceae) (% FR = 100 +/- 0) as well as of all Bignoniaceae
      and Sapindaceae species. No extracts were active against S. littoralis larvae,
      and most of them were innocuous to honey bees, with the exception of L.
      cestroides and S. meridionalis leaf extracts.

PMID- 20046903
TI  - Recreational Activities to Reduce Behavioural Symptoms in Dementia.
AB  - Few clinicians have an educational grounding in the use of nonpharmacological
      therapies for people with dementia. In this article, we explore the utility of
      recreational activities as one nonpharmacological intervention that has
      demonstrated effectiveness for reducing the behavioural symptoms of dementia. The
      implementation of effective recreational activities involves three components:
      understanding the evidence for this approach; acknowledging the need to reduce
      medications that have the potential to interfere with activity effectiveness; and
      individualizing activities so that the maximum benefit from the intervention is
      obtained.

PMID- 20046905
TI  - Culturally tailored foods and CVD prevention.
AB  - Culture plays an integral role in people's food choices and lifestyle decisions.
      Health care messages may conflict with cultural beliefs for many immigrant,
      minority, and low income populations. The multiple ways that culture can
      positively and negatively affect disease risk must be utilized in the development
      of 'culturally tailored' messages or interventions. Only through the creation of
      interventions that are meaningful and culturally-relevant can successful behavior
      stability or change occur. The recognition of current health-promoting factors is
      important to develop rapport and credibility with individuals and population
      groups in order to reduce the risk of CVD and other lifestyle-based chronic
      diseases for optimal health.

PMID- 20046904
TI  - Perceptual normalization for speaking rate III: Effects of the rate of one voice
      on perception of another.
AB  - Individuals vary their speaking rate, and listeners use the speaking rate of
      precursor sentences to adjust for these changes (Kidd, 1989). Most of the
      research on this adjustment process has focused on situations in which there was
      only a single stream of speech over which such perceptual adjustment could occur.
      Yet listeners are often faced with environments in which multiple people are
      speaking simultaneously. Each of these voices provides speaking rate information.
      The challenge for the listener is to determine which sources of information
      should apply in a speech perception situation. Three studies examined when
      listeners would use rate information from one voice to adjust their perception of
      another voice. Results suggested that if only one source of duration information
      was available, listeners used that information, regardless of the speaker or the
      speaker's spatial location. When multiple sources were available, listeners
      primarily used information from the same source as the target item. However, even
      information from a source that differed in both location and talker still
      influenced perception to a slight degree.

PMID- 20046906
TI  - EPIDEMIOLOGY MEETS CULTURAL STUDIES: STUDYING AND UNDERSTANDING YOUTH CULTURES,
      CLUBS AND DRUGS.

PMID- 20046907
TI  - Redistribution by insurance market regulation: Analyzing a ban on gender-based
      retirement annuities.
AB  - We illustrate how equilibrium screening models can be used to evaluate the
      economic consequences of insurance market regulation. We calibrate and solve a
      model of the United Kingdom's compulsory annuity market and examine the impact of
      gender-based pricing restrictions. We find that the endogenous adjustment of
      annuity contract menus in response to such restrictions can undo up to half of
      the redistribution from men to women that would occur with exogenous Social
      Security-like annuity contracts. Our findings indicate the importance of
      endogenous contract responses and illustrate the feasibility of employing
      theoretical insurance market equilibrium models for quantitative policy analysis.

PMID- 20046908
TI  - The Effect of Online Chapter Quizzes on Exam Performance in an Undergraduate
      Social Psychology Course.
AB  - Assigned textbook readings are a common requirement in undergraduate courses, but
      students often do not complete reading assignments or do not do so until
      immediately before an exam. This may have detrimental effects on learning and
      course performance. Regularly scheduled quizzes on reading material may increase
      completion of reading assignments and therefore course performance. This study
      examined the effectiveness of compulsory, mastery-based, weekly reading quizzes
      as a means of improving exam and course performance. Completion of reading
      quizzes was related to both better exam and course performance. The discussion
      includes recommendations for the use of quizzes in undergraduate courses.

PMID- 20046909
TI  - Adaptation of the U.S. Food Security Survey Module for Low-Income Pregnant
      Latinas: Qualitative Phase.
AB  - The objectives of this study were to: 1) assessed the face validity of the 18
      items US Household Food Security Scale Module (US HFSSM) among low-income
      pregnant Latinas and 2) adapt the US HFSSM to the target population. This study
      was conducted in the United States in Hartford, Connecticut where 40% of
      residents are of Latina descent. Three focus groups (N=14(total)) were held with
      pregnant and postpartum Latinas from April - June 2004 to assess the
      understanding and applicability (face validity) of the US HFSSM as well as adapt
      the US HFSSM based on their recommendations. This was followed by pre-testing
      (N=7) to make final adaptations to the US HFSSM. Overall, the items in the US
      HFSSM were clear and understandable to participants, but some questions sounded
      repetitive to them. Participants felt the questions were applicable to other
      pregnant Latinas in their community and shared food security related experiences
      and strategies. Participants recommendations led to key adaptations to the US
      HFSSM including reducing the scale to 15-items, wording statements as questions,
      including two time periods, replacing the term "balanced meals" with "healthy and
      varied", replacing the term "low cost foods" with "cheap foods" and including a
      definition of the term, and including a coping mechanism of avoiding running out
      of food. The adapted US HFSSM was found to have good face validity among pregnant
      Latinas and can be used to assess food insecurity among this vulnerable
      population.

PMID- 20046910
TI  - Biometric identification using knee X-rays.
AB  - Identification of people often makes use of unique features of the face,
      fingerprints and retina. Beyond this, a similar identifying process can be
      applied to internal parts of the body that are not visible to the unaided eye.
      Here we show that knee X-rays can be used for the identification of individual
      persons. The image analysis method is based on the wnd-charm algorithm, which has
      been found effective for the diagnosis of clinical conditions of knee joints.
      Experimental results show that the rank-10 identification accuracy using a
      dataset of 425 individuals is ~56%, and the rank-1 accuracy is ~34%. The dataset
      contained knee X-rays taken several years apart from each other, showing that the
      identifiable features correspond to specific persons, rather than the present
      clinical condition of the joint.

PMID- 20046911
TI  - Multiple demonstrations of metacognition in nonhumans: Converging evidence or
      multiple mechanisms?
AB  - Metacognition allows one to monitor and adaptively control cognitive processes.
      Reports from the last 15 years show that when given the opportunity, nonhuman
      animals selectively avoid taking difficult tests of memory or perception, collect
      more information if needed before taking tests, or "gamble" more food reward on
      correct than on incorrect responses in tests of memory and perception. I review
      representative examples from this literature, considering the sufficiency of four
      classes of mechanism to account for the metacognitive performance observed. This
      analysis suggests that many of the demonstrations of metacognition in nonhumans
      can be explained in terms of associative learning or other mechanisms that do not
      require invoking introspection or access to private mental states. Consideration
      of these accounts may prompt greater appreciation of the diversity of
      metacognitive phenomena and may inform theoretical positions about the nature of
      the mental representations underlying metacognition.

PMID- 20046913
TI  - Psychometric Properties of an Adapted Version of the U.S. Household Food Security
      Survey Module for Assessing Food Insecurity Among Low-Income Pregnant Latinas.
AB  - This study examined the internal validity of an adapted version of the U.S.
      Household Food Security Survey Module administered to a sample of 241 pregnant
      Latinas. Single-parameter logistic (Rasch) measurement model was used to assess
      the psychometric properties of the adapted module. Two of 14 questions examined
      did not fit within the acceptable range (0.70-1.30). The severity level of 12 of
      the 14 questions was similar across two time periods, before pregnancy and the
      past month of pregnancy. These findings suggest the adapted module is valid for
      use among pregnant Latinas, yet some items might not be applicable during
      pregnancy.

PMID- 20046912
TI  - Focusing the uncertainty about nonhuman metacogntion.

PMID- 20046914
TI  - Women-focused treatment agencies and process improvement: Strategies to increase
      client engagement.
AB  - Behavioral health treatment agencies often struggle to keep clients engaged in
      treatment. Women clients often have additional factors such as family
      responsibilities, financial difficulties, or abuse histories that provide extra
      challenges to remaining in care. As part of a national initiative, four women
      focused drug treatment agencies used process improvement to address treatment
      engagement. Interviews and focus groups with staff assessed the nature and extent
      of interventions. Women-focused drug treatment agencies selected relational-based
      interventions to engage clients in treatment and improved four-week treatment
      retention from 66% to 76%. Process improvement interventions in women-focused
      treatment may be useful to improve engagement.

PMID- 20046915
TI  - Rapid rheological screening to identify conditions of biomaterial hydrogelation.
AB  - Hydrogels engineered for biomedical applications consist of numerous components,
      each of which can affect the material assembly and final mechanical properties.
      We present methods that rapidly generate rheological libraries to identify
      regimes of hydrogel assembly in a large composition parameter space. This method
      conserves both material and time, and leads to critical insight into assembly
      mechanisms and mechanics, which can then be used for further materials
      development and optimization.

PMID- 20046916
TI  - Cyanoximes as effective and selective co-crystallizing agents.
AB  - The ability of cyanoxime-based synthons to act as versatile synthetic tools for
      the construction of co-crystals is demonstrated through the preparation and
      structural characterization of seven co-crystals. Cyanoximes can bind effectively
      to both five-membered and six-membered N-heterocyclic hydrogen-bond acceptors,
      and they also display selectivity towards the best acceptor (as determined using
      semi-empirical AM1 calculations) in ditopic compounds.

PMID- 20046917
TI  - Targeted Mentoring: Evaluation of a Program.
AB  - Targeted mentoring refers to mentoring aimed at a particular population. This
      article presents the evaluation of a mentoring program for lesbian, gay,
      bisexual, and transgender (LGBT) persons in social work education. Forty-three
      mentors and proteges responded to a survey regarding their program experiences.
      The results highlight the need for targeted mentoring, although some disparities
      of experience for mentors and proteges in this program are apparent. In general,
      mentors felt positive about participating, giving back to the LGBT community, and
      were more satisfied with their experiences than were the proteges, who were
      looking for more specific types of instrumental and psychosocial support.

PMID- 20046918
TI  - Cocaine Exposure Results in Formation of Dendritic Varicosity in Rat Primary
      Hippocampal Neurons.
AB  - While it has been well documented that drugs of abuse such as cocaine can cause
      enhanced progression of HIV-Associated Neuropathological Disorders (HAND), the
      underlying mechanisms mediating these effects remain poorly understood. In the
      present study, we explored the impact of cocaine exposure (I MUM and 10 MUM) on
      the dendritic beading in rat primary hippocampal neurons. Using the approach of
      transfection with green fluorescent protein, we observed significant dendritic
      swelling in hippocampal neurons exposed to 10 MUM but not 1 MUM of cocaine when
      compared with the saline treated group. Cocaine exposure also resulted in
      decreased expression of the synaptic plasticity gene, Arc as evidenced by Western
      blotting. Intriguingly, cocaine exposure of primary neurons in the presence of
      the neurotoxin-HIV envelope protein gp 120, resulted in increased enhancement of
      neuronal beading as compared with exposure of neurons to either agent alone.
      Taken together these findings imply that cocaine in co-operation with HIV protein
      exacerbates neuronal damage in the brains of HIV-infected cocaine abusers.

PMID- 20046919
TI  - Cultural Pride Reinforcement as a Dimension of Racial Socialization Protective of
      Urban African American Child Anxiety.
AB  - The study objective was to examine how parental endorsement of cultural pride
      reinforcement messages may explain African American child anxiety. Data were
      gathered from 72 African American parents and their elementary school-aged
      children. Results indicated stronger parental endorsement of cultural pride
      reinforcement messages predicted less child anxiety. Additionally parental
      endorsement of these messages moderated the relationship between child mental
      health risk factor exposure and child anxiety. Specifically in the presence of
      high exposure, children of parents who endorsed high levels of cultural pride
      reinforcement messages had significantly lower anxiety scores relative to
      children of parents who endorsed low levels of these messages. Findings indicated
      parental endorsement of these messages may be an important factor in explaining
      African American child anxiety.

PMID- 20046920
TI  - Preparative isolation and purification of flavonoids from the Chinese medicinal
      herb Belamcanda by high-speed countercurrent chromatography.
AB  - High-speed countercurrent chromatography (HSCCC) was applied for separation and
      purification of flavonoids from the extract of belamcanda. High efficiency of
      HSCCC separation was achieved on a two-phase solvent system of n-hexane-ethyl
      acetate-methanol-water (4:5:5:5, v/v) by eluting the lower mobile phase at a flow
      rate of 1.2mL/min and a revolution speed of 800 rpm. Three well-separated peaks
      were obtained in the HSCCC chromatogram and their purities were determined by
      HPLC-UV absorption spectrometry. These peaks were characterized by ESI-MS(n) and
      NMR, and the data compared with the reference standards where three peaks were
      identified as isorhamnetin, irigenin and hispidulin. The purities of each peak
      were 94, 95 and 90% respectively. In HSCCC experiment, 100 mg of the crude
      extract were separated yielding 10 mg of isorhamnetin, 8 mg of irigenin and 7 mg
      of hispidulin. HSCCC thus provides a cost-effective alternative to preparative
      scale HPLC for the semi-preparative scale separation and purification of
      flavonoids from Belamcanda.

PMID- 20046921
TI  - Two-Step Purification of Cordycepin from Cordyceps Millitaris by High-Speed
      Countercurrent Chromatography.
AB  - Cordycepin is successfully isolated and purified from Cordyceps millitaris in two
      step purification by high-speed countercurrent chromatography. Two solvent
      systems, ethyl acetate-1-butanol-water (3:2:5, v/v/v) and trichloromethane
      methanol-1-butanol-water (2:1:0.25:1, v/v/v/v), were used for the two-step
      purification. The purity of the prepared cordycepin was 98.1% according to the
      high-performance liquid chromatography analysis.

PMID- 20046922
TI  - Teaching Discrimination of Adult Gaze Direction to Children with Autism.
AB  - Three young children diagnosed with autism did not reliably locate objects in the
      environment on the basis of an adult's gaze shifts. A training program designed
      to teach gaze following used the activation of remote controlled mechanical toys
      as both prompts and consequences. Over several training sessions, toy activation
      was progressively delayed following the adult's gaze-shift cues. All of the
      children eventually came to anticipate the toy activation and locate the target
      object on the basis of the adult's gaze-shift cue alone. Discrimination of
      another person's gaze direction is discussed in relation to joint attention
      deficits in children with autism.

PMID- 20046923
TI  - Positron Emission Tomography Imaging of Hypoxia.
AB  - Hypoxia imaging has applications in functional recovery in ischemic events such
      as stroke and myocardial ischemia, but especially in tumors in which hypoxia can
      be predictive of treatment response and overall prognosis. Recently there has
      been development of imaging agents utilizing positron emission tomography for non
      invasive imaging of hypoxia. Many of these PET agents have come to the forefront
      of hypoxia imaging. Halogenated PET nitroimidazole imaging agents labeled with
      (18)F (t(1/2) = 110 m) and (124)I (t(1/2) = 110 m) have been under investigation
      for the last 25 years, with radiometal agents ((64)Cu-ATSM) being developed more
      recently. This review focuses on these positron emission tomography imaging
      agents for hypoxia.

PMID- 20046925
TI  - Most People who Think that They are Likely to Enter Psychotherapy also Think it
      is Plausible that They could have Forgotten their own Memories of Childhood
      Sexual Abuse.
AB  - Pezdek and Blandon-Gitlin (in press) found that 25% of their participants
      reported as plausible or very plausible that they themselves could have been a
      victim of childhood sexual abuse without being able to remember it. In addition,
      they found that the 25% figure increased to 61% for participants who reported
      that they were likely at some point in their life to seek psychotherapy. Given
      past work showing that it is easier to implant a false memory for plausible
      events, and counter to Pezdek and Blandon-Gitlin's conclusions, these data point
      to a substantial danger of implanting false memories of childhood sexual abuse
      during therapy in many people and in most people who are likely to go into
      therapy. Theoretical issues regarding plausibility are discussed.

PMID- 20046924
TI  - Inhibition of transcription by platinum antitumor compounds.
AB  - Cisplatin, carboplatin, and oxaliplatin are three FDA-approved members of the
      platinum anticancer drug family. These compounds induce apoptosis in tumor cells
      by binding to nuclear DNA, forming a variety of structural adducts and triggering
      cellular responses, one of which is the inhibition of transcription. In this
      report we present (i) a detailed review of the structural investigations of
      various Pt-DNA adducts and the effects of these lesions on global DNA geometry;
      (ii) research detailing inhibition of cellular transcription by Pt-DNA adducts;
      and (iii) a mechanistic analysis of how DNA structural distortions induced by
      platinum damage may inhibit RNA synthesis in vivo. A thorough understanding of
      the molecular mechanism of action of platinum antitumor agents will aid in the
      development of new compounds in the family.

PMID- 20046927
TI  - Introducing Complementary and Alternative Therapies.

PMID- 20046928
TI  - Excited-State Proton Transfer in Chiral Environments: Photoracemization of
      BINOLs.
AB  - We have studied excited-state proton transfer (ESPT) from chiral proton donors to
      chiral and achiral acceptors. The key role of the exergonicity of the reaction
      and the transition-state position along the reaction coordinate for the existence
      of an enantiomeric effect was established. This effect was observed for "super"
      photoacids (DeltaG ? 0) and vanished for endergonic reactions (DeltaG > 0) where
      a "late" transition state similar to planar achiral binaphtholate anion occurs.
      As a result, photoracemization was observed, as confirmed by circular dichroism
      spectroscopy. The photoracemization effects were studied for several chiral
      photoacids (BINOLs and their ethers) and proton acceptors (amines, aminoalcohols,
      and water) using UV-vis, steady-state fluorescence, and time-resolved
      fluorescence spectroscopies. The nature of the solvent and the proton acceptor,
      as well as the chemical structure of the BINOL, played a pivotal role in the
      photochemical reactivity of the system. Two proposed pathways competed for
      photoracemization: excited-state inter- and intra-molecular proton transfer, the
      former being more effective. Irradiation of the dimethoxy BINOL derivative, which
      lacks an acidic proton and cannot undergo ESPT, produced no appreciable reaction
      or racemization.

PMID- 20046929
TI  - QM/MM Simulation on P450 BM3 Enzyme Catalysis Mechanism.
AB  - Using a structure generated by induced fit modeling of the protein-ligand
      complex, the reaction path for hydrogen atom abstraction in P450 BM3 is studied
      by means of mixed QM/MM methods to determine the structures and energetics along
      the reaction path. The IFD structure is suitable for hydrogen atom abstraction at
      the omega-1 position. The electronic structures obtained are similar to those
      observed in P450 cam. We show that the barrier for the hydrogen abstraction step
      from QM/MM modeling is 13.3 kcal/mol in quartet and 15.6 kcal/mol in doublet.
      Although there is some strain energy present in the ligand, the activation
      barrier is not dramatically affected. A crystal water molecule, HOH502, plays a
      role as catalyst and decreases the activation barrier by about 2 kcal/mol and
      reaction energy by about 3-4 kcal/mol. In order to achieve reactive chemistry at
      the remaining experimentally observed positions in the hydrocarbon tail of the
      ligand, other structures would have to be utilized as a starting point for the
      reaction. Finally, the present results still leave open the question of whether
      DFT methods provide an accurate computation of the barrier height in the P450
      hydrogen atom abstraction reaction.

PMID- 20046926
TI  - PET Imaging of Angiogenesis.
AB  - Angiogenesis is a highly-controlled process that is dependent on the intricate
      balance of both promoting and inhibiting factors, involved in various
      physiological and pathological processes. A comprehensive understanding of the
      molecular mechanisms that regulate angiogenesis has resulted in the design of new
      and more effective therapeutic strategies. Due to insufficient sensitivity to
      detect therapeutic effects by using standard clinical endpoints or by looking for
      physiological improvement, a multitude of imaging techniques have been developed
      to assess tissue vasculature on the structural, functional and molecular level.
      Imaging is expected to provide a novel approach to noninvasively monitor
      angiogenesis, to optimize the dose of new antiangiogenic agents and to assess the
      efficacy of therapies directed at modulation of the angiogenic process. All these
      methods have been successfully used preclinically and will hopefully aid in
      antiangiogenic drug development in animal studies. In this review article, the
      application of PET in angiogenesis imaging at both functional and molecular level
      will be discussed. For PET imaging of angiogenesis related molecular markers, we
      emphasize integrin alpha(v)beta(3), VEGF/VEGFR, and MMPs. 

PMID- 20046930
TI  - The SLIM Study: Slo-Niacin(r) and Atorvastatin Treatment of Lipoproteins and
      Inflammatory Markers in Combined Hyperlipidemia.
AB  - BACKGROUND: The combination of niacin and statin has proven value in
      hyperlipidemia management and heart disease prevention. However, the efficacy of
      the non-prescription time-release niacin, Slo-Niacin(r), is little studied alone
      and not at all with atorvastatin. We gave Slo-Niacin(r) and atorvastatin, singly
      and together to determine efficacy on the combined abnormalities of triglyceride,
      LDL and HDL.  METHODS: 42 men and women with LDL-C>130mg/dL HDL-C <45 (men or
      55mg/dL (women) were randomized to 3 months of atorvastatin 10 mg/day or
      incremental doses of Slo-Niacin(r) to 1500 mg/day. The alternate drug was added
      in the next 3-month segment. Lipid profiles and transaminases were measured
      monthly and other measures at baseline and the end of each treatment sequence. 
      RESULTS: Mean entry lipids (mg/dL) were: TG 187, LDL-C 171, and HDL-C 39. Mean
      BMI was 32.6 Kg/m(2). Monotherapy with Slo-Niacin(r) decreased median
      triglyceride 15%, mean LDL-C 12% and non-HDL-C 15% and increased HDL-C 8%.
      Atorvastatin decreased median triglyceride 26%, and mean LDL-C 36%, non-HDL-C 36%
      and increased HDL-C 6%. Combined therapy decreased median triglyceride 33% and
      mean LDL-C and non-HDL-C each 43%. HDL-C increased 10% (all p<0.001). Median
      remnant-like lipoprotein-C decreased 55%, mean apo-B 40%, median hsCRP 23% (all
      p<0.05), TNFa 12% and no change in IL-6. Mean LDL buoyancy increased 15%, apo-A-I
      5% and median HDL(2)-C 20% (all p<0.05). ALT declined with Slo-Niacin(r)
      treatment alone compared to atorvastatin and also decreased when Slo-Niacin(r)
      was added to atorvastatin. Six subjects dropped out, 3 for niacin related
      symptoms.  CONCLUSIONS: Slo-Niacin(r) 1.5g/day with atorvastatin 10 mg/day
      improved lipoprotein lipids, apoproteins and inflammation markers without
      hepatotoxicity. Slo-Niacin(r) deserves further study as a cost-effective
      treatment of hyperlipidemia.

PMID- 20046931
TI  - PARTITION EFFICIENCY OF NEWLY DESIGNED LOCULAR MULTILAYER COIL FOR COUNTERCURRENT
      CHROMATOGRAPHIC SEPARATION OF PROTEINS USING SMALL-SCALE CROSS-AXIS COIL PLANET
      CENTRIFUGE WITH AQUEOUS-AQUEOUS POLYMER PHASE SYSTEMS.
AB  - Countercurrent chromatographic performance of the locular multilayer coil
      separation column newly designed in our laboratory was evaluated in terms of
      theoretical plate number, peak resolution and retention of the stationary phase
      in protein separation with an aqueous polymer phase system using the small-scale
      cross-axis coil planet centrifuge (X-axis CPC) fabricated in our laboratory. The
      locular column was made from 1.0 mm I.D., 2.0 mm O.D. or 1.5 mm I.D., 2.5 mm O.D.
      PTFE tubing compressed with a pair of hemostat at 2 or 4 cm intervals. The
      protein separation was performed using a set of stable proteins including
      cytochrome C, myoglobin and lysozyme with the 12.5% (w/w) polyethylene glycol
      1000 and 12.5% (w/w) dibasic potassium phosphate system under 1000 rpm of column
      revolution. The 1.5 mm I.D., 2.5 mm O.D. locular tubing compressed at 2 cm
      intervals yielded better partition efficiencies than the non-clamped tubing using
      both lower and upper mobile phases with satisfactory retention of the stationary
      phase. The overall results suggest that the newly designed locular multilayer
      coil is useful to the preparative separation of proteins with aqueous-aqueous
      polymer phase system using our small-scale X-axis CPC.

PMID- 20046932
TI  - Nonverbal Social Skills of Adults with Mild Intellectual Disability Diagnosed
      with Depression.
AB  - Depression is one of the most common psychiatric disorders in adults with
      intellectual disability (ID), yet little is known about depressive behaviors in
      an ID population. This study examined the nonverbal social skills of 18 adults
      with mild ID diagnosed with depression and a matched sample of adults with mild
      ID without depression. Nonverbal social skills were coded from videotapes of
      actual social interactions. Results indicate that adults with mild ID diagnosed
      with depression evidence a profile of maladaptive nonverbal social skills
      including limited body movement, a restricted range of facial expressions,
      infrequent smiling, speaking in a flat and quiet voice, and taking a long time to
      respond to the questions or comments of a social partner. Findings from this
      study have implications for enhancing the early detection and diagnosis of
      depression and guiding theories of and treatments for depression in an ID
      population.

PMID- 20046933
TI  - Accommodating Covariates in ROC Analysis.
AB  - Classification accuracy is the ability of a marker or diagnostic test to
      discriminate between two groups of individuals, cases and controls, and is
      commonly summarized using the receiver operating characteristic (ROC) curve. In
      studies of classification accuracy, there are often covariates that should be
      incorporated into the ROC analysis. We describe three different ways of using
      covariate information. For factors that affect marker observations among
      controls, we present a method for covariate adjustment. For factors that affect
      discrimination (i.e. the ROC curve), we describe methods for modelling the ROC
      curve as a function of covariates. Finally, for factors that contribute to
      discrimination, we propose combining the marker and covariate information, and
      ask how much discriminatory accuracy improves with the addition of the marker to
      the covariates (incremental value). These methods follow naturally when
      representing the ROC curve as a summary of the distribution of case marker
      observations, standardized with respect to the control distribution.

PMID- 20046934
TI  - Countercurrent Chromatographic Separation of Lipophilic Ascorbic Acid Derivatives
      and Extract from Kadsura Coccinea Using Hydrophobic Organic-Aqueous Two-Phase
      Solvent Systems.
AB  - Countercurrent chromatographic (CCC) separation of lipophilic ascorbic acid
      derivatives and the crude extract from Kadsura Coccinea was performed using the
      type-J multilayer coil planet centrifuge with a hydrophobic organic-aqueous two
      phase solvent system composed of n-hexane/ethyl acetate/ethanol/aqueous 0.1%
      trifluoroacetic acid at the volume ratio of (5 : 5 : 6 : 2). The lipophilic
      ascorbic acid derivatives were separated in the order of L-ascrobyl 2,6
      dibutyrate, L-ascorbyl 6-palmitate and L-ascorbyl 6-stearate by eluting the lower
      phase as the mobile phase, and L-ascorbyl 2,6-dipalmitate was separated by
      eluting the upper phase at the opposite direction. The above solvent system was
      then applied to the CCC separation of the extract prepared from K. coccinea. With
      lower phase mobile, the extract was mainly separated into two peaks corresponding
      to lignans and triterpenoids accordingly. The HPLC analysis of the fractions
      showed that the former peak contained Kadsulignan N, Schizandrin H and
      Neokadsuranin as lignans, and the latter peak, Micranoic acid A, Neokadsuranic
      acid B and beta-Sitosterol as triterpenoids. The overall results indicate that
      the hydrophobic organic-aqueous two-phase solvent system used in the present
      studies was useful for the CCC separation of lignans and triterpenoids present in
      the natural products.

PMID- 20046935
TI  - Near-infrared squaraine dyes for fluorescence enhanced surface assay.
AB  - Commercially available, near-infrared fluorescent squaraine dyes (Seta-635 and
      Seta-670) were covalently bound to antibodies and employed insurface enhanced
      immunoassay. From fluorescence intensity and lifetime changes determined for a
      surface which had been coated with silver nanoparticles as well as a non-coated
      glass surface, both labelled compounds exhibited a 15 to 20-fold enhancement of
      fluorescence on the silver coated surface compared to that achieved on the non
      coated surface. In addition, the fluorescence lifetime changes drastically for
      both labels in the case of silver-coated surfaces. The fluorescence signal
      enhancement obtained for the two dyes was greater than that previously recorded
      for Rhodamine Red-X and AlexaFluor-647 labels.

PMID- 20046936
TI  - Organization of lower rim O-alkylated p-phosphonic acid calix[4]arenes.
AB  - Lower rim O-methyl, -n-butyl, and n-octadecyl calix[4]arenes bearing p-phosphonic
      acid groups on the upper rim have been prepared in high yield, compounds 12-14.
      Where possible the compounds have been characterized in the solid state using X
      ray diffraction, or as the precursor phosphate esters or a cesium salt. The cone
      conformation ethyl phosphate ester for the octadecyl compound crystallizes in a
      bi-layer 39.1 A thick which approaches the 40 A of biological membranes. The 1,3
      alternate cone conformation of the cesium salt of the O-methyl phosphonic acid
      has a metal ion coordinated to two methoxy groups, four O-P (two from neighboring
      calixarenes), and two eta(3)-C(3) moieties from two 1,3-disposed aromatic rings.
      MALDI-TOF spectra of compounds 12-14 show successive peaks corresponding to 15,
      33 and 16 calixarene units, which is consistent with the intra-molecular H
      bonding capabilities of the di-protic phosphonic acid groups where the
      calixarenes are arranged into layers, including bilayers.

PMID- 20046937
TI  - Recent Applications of Imines as Key Intermediates in the Synthesis of Alkaloids
      and Novel Nitrogen Heterocycles.
AB  - One of the major challenges in contemporary synthetic organic chemistry is the
      design and development of new tactics and strategies and their application to
      concise and efficient syntheses of biologically active natural products.
      Strategies that utilize reactions that enable the rapid assembly of the skeletal
      framework of such targets are thus especially attractive. In this context, we
      have developed novel applications of imine chemistry in Mannich and related
      reactions, cascade processes, and multicomponent reactions to rapidly assemble
      structural subunits common to diverse families of alkaloids. The practical
      utility of these chemistries is evidenced by their use in the execution of facile
      total syntheses of (+/-)-epilupinine (1), (+/-)-tashiromine (2), (-)-epimyrtine
      (3), and (+/-)-roelactamine (4) as well as other nitrogen heterocycles of
      potential biological interest.

PMID- 20046938
TI  - BIS, BAS, and response conflict: Testing predictions of the revised reinforcement
      sensitivity theory.
AB  - Gray's (1970) reinforcement sensitivity theory (RST) was recently updated (Gray &
      McNaughton, 2000), but the changes have not received extensive empirical
      validation. The study tests three novel predictions of the revised RST. First,
      the behavioral activation system (BAS) is expected to be sensitive to both
      conditioned and unconditioned incentives. Second, the behavioral inhibition
      system (BIS) is expected to be sensitive to conflicting incentives such as
      between unconditioned and conditioned stimuli, and not to avoidance responses or
      aversive stimuli alone. Third, during approach-avoidance conflicts only, BAS is
      expected to moderate BIS responses to conflict such that individuals with high
      BAS show the strongest effect of BIS. In order to test these hypotheses, we
      developed a novel incentive task that crosses approach/avoidance conditioned
      responses to appetitive/aversive unconditioned stimuli. Conflict between
      unconditioned and conditioned stimuli occurred on the approach-aversive and avoid
      appetitive trials. Results confirm the predictions and provide support for the
      revised RST.

PMID- 20046940
TI  - Triangular Helical Column for Centrifugal Countercurrent Chromatography.
AB  - Effective column space and stationary phase retention have been improved by
      changing the configuration of the helical column originally used for toroidal
      coil countercurrent chromatography. The use of an equilateral triangular core for
      the helix column doubles effective column space and retains the stationary phase
      over 40% of the total column capacity without increasing the column pressure. The
      present results suggest that the stationary phase retention and the peak
      resolution will be further improved using new column designs fabricated by a new
      technology called "laser sintering for rapid prototyping."

PMID- 20046939
TI  - Cortisol Reactivity, Maternal Sensitivity, and Infant Preference for Mother's
      Familiar Face and Rhyme in 6-Month-Old Infants.
AB  - This study investigated how cortisol (stress) reactivity and mothers' behavioral
      sensitivity affect familiarity preferences in 6-month-old infants. Relations
      between sensitivity and stress were explored using saliva samples taken from
      mothers and infants before, and 20-min after, two preferential looking
      experiments. Photographs and voice recordings from infants' mothers were
      incorporated into standard visual preference tasks. Sensitivity was assessed by
      determining the degree of behavioral synchrony between mother and infant from a
      10-min interaction period preceding the preferential looking experiments. Results
      showed that decreasing infant cortisol reactivity and greater maternal
      sensitivity were associated with familiarity preferences for mother's face
      stimuli. For the experiment with voice stimuli, a sex difference was obtained in
      the relationship between the directionality of cortisol reactivity and
      familiarity preferences. Results are related to a parallel study with 3-month-old
      infants (Thompson & Trevathan, 2008), and issues are discussed in terms of
      infants' developing emotional independence from mother.

PMID- 20046941
TI  - Supramolecular synthesis based on a combination of hydrogen- and halogen bonds.
AB  - A family of supramolecular reagents containing two different binding sites,
      pyridine and amino-pyrimidine, were allowed to react with iodo- or bromo
      substituted benzoic acids in order to assemble individual molecules into larger
      architectures with precise intermolecular interactions, using a combination of
      hydrogen- and halogen-bonds. The hydrogen-bond based amino-pyrimidine/carboxylic
      acid or amino-pyrimidinium/carboxylate synthons are responsible for the assembly
      of the primary structural motif in every case (7/7 times, 100% supramolecular
      yield), while Icdots, three dots, centeredN, Brcdots, three dots, centeredN, and
      Icdots, three dots, centeredO, halogen bonds play a structural supporting role by
      organizing these supermolecules into extended 1-D and 2-D architectures (5/7
      times, 71% supramolecular yield). These results illustrate how two different non
      covalent interactions can be employed side-by-side in the reliable construction
      of extended molecular solid-state networks with predictable connectivity and
      dimensionality.

PMID- 20046942
TI  - Photosensitized Singlet Oxygen Production upon Two-Photon Excitation of Single
      Walled Carbon Nanotubes and Their Functionalized Analogs.
AB  - Single-walled carbon nanotubes (SWNTs) functionalized with -COOH (along with some
      sulphonation and nitration), and/or modified with chitosan were prepared and
      tested for their singlet oxygen ((1)O(2)) production. The emission from (1)O(2)
      observed upon SWNT irradiation at 532 nm was due to a two-photon process, while
      (1)O(2) production via excitation at 355 nm occurred through a conventional one
      photon pathway. The relative quantum yield of (1)O(2) production at excitation
      wavelength of 532 nm was found to be 0.00, 0.07-0.13 and 0.24-0.54 for highly
      functionalized, partially-functionalized and non-functionalized SWNT samples
      respectively. The nanotube-mediated generation of (1)O(2) may find applications
      in both targeted destruction of tumor cells and selective degradation of drug
      molecules. Our research provides a practical approach to modulate the production
      of reactive oxygen species from SWNTs via surface functionalization/modification.

PMID- 20046943
TI  - The influence of visual feedback and register changes on sign language
      production: A kinematic study with deaf signers.
AB  - Speakers monitor their speech output by listening to their own voice. However,
      signers do not look directly at their hands and cannot see their own face. We
      investigated the importance of a visual perceptual loop for sign language
      monitoring by examining whether changes in visual input alter sign production.
      Deaf signers produced American Sign Language (ASL) signs within a carrier phrase
      under five conditions: blindfolded, wearing tunnel-vision goggles, normal
      (citation) signing, shouting, and informal signing. Three-dimensional movement
      trajectories were obtained using an Optotrak Certus system. Informally produced
      signs were shorter with less vertical movement. Shouted signs were displaced
      forward and to the right and were produced within a larger volume of signing
      space, with greater velocity, greater distance traveled, and a longer duration.
      Tunnel vision caused signers to produce less movement within the vertical
      dimension of signing space, but blind and citation signing did not differ
      significantly on any measure, except duration. Thus, signers do not "sign louder"
      when they cannot see themselves, but they do alter their sign production when
      vision is restricted. We hypothesize that visual feedback serves primarily to
      fine-tune the size of signing space rather than as input to a comprehension-based
      monitor.

PMID- 20046944
TI  - What Patients and Families Don't Hear: Backstage Communication in Hospice
      Interdisciplinary Team Meetings.
AB  - Backstage communication has been shown to play a vital role in a bona fide
      group's teamwork. Hospice interdisciplinary teams are considered bona fide
      groups, and hospice interdisciplinary team meetings constitute backstage
      communication because they occur away from patients and families. Video
      recordings of interdisciplinary team meetings were systematically coded for
      backstage communication mess ages and the extent to which different
      interdisciplinary team members participated in backstage communication was
      explored. Results revealed that predominant backstage communication messages
      included offering of impressions and formal reporting. The sharing of backstage
      messages in interdisciplinary team meetings enable hospice staff to manage
      emotions in the safety of the backstage as well as prepare for frontstage
      professionalism.

PMID- 20046945
TI  - Electrochemical Immunosensors for Interleukin-6. Comparison of Carbon Nanotube
      Forest and Gold Nanoparticle platforms.
AB  - Electrochemical immunosensors based on single wall nanotube (SWNT) forests and 5
      nm glutathione-protected gold nanoparticles (GSH-AuNP) were developed and
      compared for the measurement of human cancer biomarker interleukin-6 (IL-6) in
      serum. Detection was based on sandwich immunoassays using multiple (14-16)
      horseradish peroxidase labels conjugated to a secondary antibody. Performance was
      optimized by effective blocking of non-specific binding (NSB) of the labels using
      bovine serum albumin. The GSH-AuNP immunosensor gave a detection limit (DL) of 10
      pg mL(-1) IL-6 (500 amol mL(-1)) in 10 muL calf serum, which was 3-fold better
      than 30 pg mL(-1) found for the SWNT forest immunosensor for the same assay
      protocol. The GSH-AuNPs platform also gave a much larger linear dynamic range (20
      4000 pg mL(-1)) than the SWNT system (40-150 pg mL(-1)), but the SWNTs had 2-fold
      better sensitivity in the low pg mL(-1) range.

PMID- 20046946
TI  - gamma-H2AX as a biomarker of DNA damage induced by ionizing radiation in human
      peripheral blood lymphocytes and artificial skin.
AB  - Ionizing radiation (IR) exposure is inevitable in our modern society and can lead
      to a variety of deleterious effects including cancer and birth defects. A
      reliable, reproducible and sensitive assessment of exposure to IR and the
      individual response to that exposure would provide much needed information for
      the optimal treatment of each donor examined. We have developed a diagnostic test
      for IR exposure based on detection of the phosphorylated form of variant histone
      H2AX (gamma-H2AX), which occurs specifically at sites of DNA double-strand breaks
      (DSBs). The cell responds to a nascent DSB through the phosphorylation of
      thousands of H2AX molecules flanking the damaged site. This highly amplified
      response can be visualized as a gamma-H2AX focus in the chromatin that can be
      detected in situ with the appropriate antibody. Here we assess the usability of
      gamma-H2AX focus formation as a possible biodosimeter for human exposure to IR
      using peripheral blood lymphocytes irradiated ex vivo and three-dimensional
      artificial models of human skin biopsies. In both systems, the tissues were
      exposed to 0.2-5 Gy, doses of IR that might be realistically encountered in
      various scenarios such as cancer radiotherapies or accidental exposure to
      radiation. Since the gamma-H2AX response is maximal 30 minutes after exposure and
      declines over a period of hours as the cells repair the damage, we examined the
      time limitations of the useful detectibility of gamma-H2AX foci. We report that a
      linear response proportional to the initial radiation dose was obtained 48 hours
      and 24 hours after exposure in blood samples and skin cells respectively. Thus,
      detection of gamma-H2AX formation to monitor DNA damage in minimally invasive
      blood and skin tests could be useful tools to determine radiation dose exposure
      and analyze its effects on humans.

PMID- 20046947
TI  - Extracting Kinetic and Stationary Distribution Information from Short MD
      Trajectories via a Collection of Surrogate Diffusion Models.
AB  - Low-dimensional stochastic models can summarize dynamical information and make
      long time predictions associated with observables of complex atomistic systems.
      Maximum likelihood based techniques for estimating low-dimensional surrogate
      diffusion models from relatively short time series are presented. It is found
      that a heterogeneous population of slowly evolving conformational degrees of
      freedom modulates the dynamics. This underlying heterogeneity results in a
      collection of estimated low-dimensional diffusion models. Numerical techniques
      for exploiting this finding to approximate skewed histograms associated with the
      simulation are presented. In addition, statistical tests are also used to assess
      the validity of the models and determine physically relevant sampling
      information, e.g. the maximum sampling frequency at which one can discretely
      sample from an atomistic time series and have a surrogate diffusion model pass
      goodness-of-fit tests. The information extracted from such analyses can possibly
      be used to assist umbrella sampling computations as well as help in approximating
      effective diffusion coefficients. The techniques are demonstrated on simulations
      of Adenylate Kinase.

PMID- 20046948
TI  - Origin of Substituent Effects in Edge-to-Face Aryl-Aryl Interactions.
AB  - Substituent effects in the edge-to-face configuration of the benzene dimer have
      been studied using modern density functional theory. An accurate interaction
      potential energy curve has been computed for the unsubstituted dimer using ab
      initio methods with large basis sets. The recommended binding energy for the edge
      to-face benzene dimer is 2.31 kcal mol(-1), estimated at the counterpoise
      corrected CCSD(T)/aug-cc-pVTZ level of theory. For both edge-ring and face-ring
      substituted dimers, interaction energies correlate with sigma(m) for the
      substituents, indicating that substituent effects can be understood qualitatively
      in terms of simple electrostatic effects, although in the latter case dispersion
      results in some scatter in the data. In contrast to prevailing models of
      substituent effects in benzene dimers, polarization of the pi-system of the
      substituted ring does not induce substituent effects. For edge-ring-substituted
      dimers, substituent effects arise from differential electrostatic interactions
      between the hydrogens on the substituted ring and the pi-cloud of the face ring
      and direct interactions of the substituents with the unsubstituted ring. For face
      ring-substituted dimers, substituent effects arise from direct electrostatic and
      dispersion interactions of the substituents with the edge ring. Substituents with
      sigma(m) > 0.12 favor edge ring substitution while for sigma(m) < 0.12
      substitution on the face ring is preferred.

PMID- 20046949
TI  - Collective Self-Esteem as a Coping Resource for Male-to-Female Transsexuals.
AB  - The fear of experiencing discrimination often provokes symptoms of psychological
      distress. One coping resource is positive identification with one's social group
      known as collective self-esteem. This preliminary study investigated whether
      collective self-esteem was related to fears regarding a transsexual identity and
      psychological distress among 53 self-identified male-to-female transsexuals (mean
      age = 50.79). Participants were recruited from transgender events held in Arizona
      and California. The majority (81%) reported living full-time as women (mean
      length of time living as a woman = 6.33 years). Negative feelings about the
      transsexual community and fears regarding the impact of a transsexual identity
      were positively related to psychological distress. A regression model revealed
      that the fear of how a transsexual identity would affect one's life was the best
      predictor of the severity of psychological distress. These results are consistent
      with findings from other historically marginalized groups whereby the stress of
      being stigmatized by society adversely affects mental health.

PMID- 20046950
TI  - A note on exact image reconstruction from a limited number of projections.
AB  - In a recent paper in this journal by Kesidis and Papamarkos "A new method for the
      exact reconstruction of any gray-scale image from its projections is proposed."
      In this note we point out that this method is a special case of a well-known
      approach (peeling) and that it can produce exact reconstructions only under
      assumptions that are not realistic for practical methods of data collection.
      Further, we point out that some statements made in the paper regarding
      disadvantages of the algebraic reconstruction techniques (ART) as compared to the
      method of the paper are false.

PMID- 20046951
TI  - FAMILY STRUCTURE TRANSITIONS AND MATERNAL PARENTING STRESS.
AB  - Data from the Fragile Families and Child Wellbeing Study (N = 4,176) are used to
      examine family structure transitions and maternal parenting stress. Using
      multilevel modeling, we find that mothers who exit coresidential relationships
      with biological fathers or enter coresidential relationships with nonbiological
      fathers report higher levels of parenting stress than mothers in stable
      coresidential relationships. Mothers who enter coresidential relationships with
      biological fathers report lower levels of parenting stress than mothers who
      remain single. Mothers' resources, especially their relationships with biological
      fathers, account for most of the associations between transitions and parenting
      stress, with posttransition resources being more important than pretransition
      resources. Mothers with high levels of education are less affected by transitions
      than mothers with less education.

PMID- 20046952
TI  - Correcting Instrumental Variables Estimators for Systematic Measurement Error.
AB  - Instrumental variables (IV) estimators are well established to correct for
      measurement error on exposure in a broad range of fields. In a distinct prominent
      stream of research IV's are becoming increasingly popular for estimating causal
      effects of exposure on outcome since they allow for unmeasured confounders which
      are hard to avoid. Because many causal questions emerge from data which suffer
      severe measurement error problems, we combine both IV approaches in this article
      to correct IV-based causal effect estimators in linear (structural mean) models
      for possibly systematic measurement error on the exposure. The estimators rely on
      the presence of a baseline measurement which is associated with the observed
      exposure and known not to modify the target effect. Simulation studies and the
      analysis of a small blood pressure reduction trial (n = 105) with treatment
      noncompliance confirm the adequate performance of our estimators in finite
      samples. Our results also demonstrate that incorporating limited prior knowledge
      about a weakly identified parameter (such as the error mean) in a frequentist
      analysis can yield substantial improvements.

PMID- 20046953
TI  - Regression calibration for dichotomized mismeasured predictors.
AB  - Epidemiologic research focuses on estimating exposure-disease associations. In
      some applications the exposure may be dichotomized, for instance when threshold
      levels of the exposure are of primary public health interest (e.g., consuming 5
      or more fruits and vegetables per day may reduce cancer risk). Errors in exposure
      variables are known to yield biased regression coefficients in exposure-disease
      models. Methods for bias-correction with continuous mismeasured exposures have
      been extensively discussed, and are often based on validation substudies, where
      the "true" and imprecise exposures are observed on a small subsample. In this
      paper, we focus on biases associated with dichotomization of a mismeasured
      continuous exposure. The amount of bias, in relation to measurement error in the
      imprecise continuous predictor, and choice of dichotomization cut point are
      discussed. Measurement error correction via regression calibration is developed
      for this scenario, and compared to naively using the dichotomized mismeasured
      predictor in linear exposure-disease models. Properties of the measurement error
      correction method (i.e., bias, mean-squared error) are assessed via simulations.

PMID- 20046954
TI  - Novel Design for Centrifugal Countercurrent Chromatography: I. Zigzag Toroidal
      Column.
AB  - The toroidal coil using an equilateral triangular core has improved both
      retention of the stationary phase and peak resolution of the conventional
      toroidal coil in centrifugal countercurrent chromatography. To further improve
      the retention of stationary phase and peak resolution, a novel zigzag toroidal
      coil was designed and the performance of the system was evaluated at various flow
      rates. The results indicated that both retention of stationary phase and peak
      resolution were improved as the flow rate was decreased. Modification of the
      tubing by pressing at given intervals with a pair of pliers improved the peak
      resolution without increasing the column pressure. All these separations were
      performed under low column pressure indicating the separation can be further
      improved by increasing the column length and/or revolution speed without damaging
      the separation column.

PMID- 20046955
TI  - A Survey of Solvents for the Conrad-Limpach Synthesis of 4-Hydroxyquinolones.
AB  - A study on the synthesis of a 4-hydroxyquinoline derivative using the Conrad
      Limpach reaction led to the identification of inexpensive and user-friendly
      solvents for this thermal condensation.

PMID- 20046956
TI  - Bias, efficiency, and agreement for group-testing regression models.
AB  - Group testing involves pooling individual items together and testing them
      simultaneously for a rare binary trait. Whether the goal is to estimate the
      prevalence of the trait or to identify those individuals that possess it, group
      testing can provide substantial benefits when compared to testing subjects
      individually. Recently, group-testing regression models have been proposed as a
      way to incorporate covariates when estimating trait prevalence. In this paper, we
      examine these models by comparing fits obtained from individual and group testing
      samples. Relative bias and efficiency measures are used to assess the accuracy
      and precision of the resulting estimates using different grouping strategies. We
      also investigate the agreement of individual and group-testing regression
      estimates for various grouping strategies and the effects of group size
      selection. Depending on how groups are formed, our results show that group
      testing regression models can perform very well when compared to the analogous
      models based on individual observations. However, different grouping strategies
      can provide very different results in finite samples.

PMID- 20046958
TI  - Sequence Encoders Enable Large-Scale Lexical Modeling: Reply to Bowers and Davis
      (2009).
AB  - Sibley, Kello, Plaut, and Elman (2008) proposed the sequence encoder as a model
      that learns fixed-width distributed representations of variable-length sequences.
      In doing so, the sequence encoder overcomes problems that have restricted models
      of word reading and recognition to processing only monosyllabic words. Bowers and
      Davis (in press) recently claimed that the sequence encoder does not actually
      overcome the relevant problems, and hence is not a useful component of large
      scale word reading models. In this reply, it is noted that the sequence encoder
      has facilitated the creation of large-scale word reading models. The reasons for
      this success are explained, and stand as counterarguments to claims made by
      Bowers and Davis.

PMID- 20046959
TI  - PREPARATIVE ISOLATION OF ISORHAMNETIN FROM STIGMA MAYDIS USING HIGH-SPEED
      COUNTERCURRENT CHROMATOGRAPHY.
AB  - Preparative high-speed countercurrent chromatography (HSCCC) has been
      successfully used for the isolation and purification of isorhamnetin from Stigma
      maydis. This was achieved in two stages: the first separation was performed with
      a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water
      (HEMW) at a volume ratio of 5:5:5:5, yielding isorhamnetinat 65.6 %, which is
      followed by the second run using a two-phase solvent system composed of HEMW
      5:5:6:4, v/v. From 700 mg of the crude extract 11.8 mg of isorhamnetin was
      obtained at a high purity of 98%. The final identification was performed by MS,
      (1)H-NMR and (13)C-NMR spectra.

PMID- 20046957
TI  - Interplay of metal ions and urease.
AB  - Urease, the first enzyme to be crystallized, contains a dinuclear nickel
      metallocenter that catalyzes the decomposition of urea to produce ammonia, a
      reaction of great agricultural and medical importance. Several mechanisms of
      urease catalysis have been proposed on the basis of enzyme crystal structures,
      model complexes, and computational efforts, but the precise steps in catalysis
      and the requirement of nickel versus other metals remain unclear. Purified
      bacterial urease is partially activated via incubation with carbon dioxide plus
      nickel ions; however, in vitro activation also has been achieved with manganese
      and cobalt. In vivo activation of most ureases requires accessory proteins that
      function as nickel metallochaperones and GTP-dependent molecular chaperones or
      play other roles in the maturation process. In addition, some microorganisms
      control their levels of urease by metal ion-dependent regulatory mechanisms.

PMID- 20046960
TI  - Bacillus Calmette-Guerin immunotherapy for urothelial carcinoma of the bladder.
AB  - Mycobacterium bovis bacille Calmette-Guerin (BCG) is one of the great success
      stories of immunotherapy as a treatment for superficial urothelial carcinoma of
      the bladder. Despite clinical effectiveness in over 50% of patients, the high
      incidence of local side effects and presence of nonresponders has led to efforts
      to improve the therapy. Recent advances have suggested a role for neutrophils and
      TNF-related apoptosis-inducing ligand (TRAIL) in the antitumor inflammatory
      response. Cell wall components of mycobacteria alone, lowered doses of BCG, and
      combination with cytokines have been studied as ways to improve the immune
      response associated with BCG and/or reduce toxicity. This review will discuss the
      clinical use of BCG, its proposed mechanism of action, and directions of future
      research to improve efficacy and decrease side effects.

PMID- 20046962
TI  - Micropower CMOS Integrated Low-Noise Amplification, Filtering, and Digitization
      of Multimodal Neuropotentials.
AB  - Electrical activity in the brain spans a wide range of spatial and temporal
      scales, requiring simultaneous recording of multiple modalities of
      neurophysiological signals in order to capture various aspects of brain state
      dynamics. Here, we present a 16-channel neural interface integrated circuit
      fabricated in a 0.5 mum 3M2P CMOS process for selective digital acquisition of
      biopotentials across the spectrum of neural signal modalities in the brain,
      ranging from single spike action potentials to local field potentials (LFP),
      electrocorticograms (ECoG), and electroencephalograms (EEG). Each channel is
      composed of a tunable bandwidth, fixed gain front-end amplifier and a
      programmable gain/resolution continuous-time incremental DeltaSigma analog-to
      digital converter (ADC). A two-stage topology for the front-end voltage amplifier
      with capacitive feedback offers independent tuning of the amplifier bandpass
      frequency corners, and attains a noise efficiency factor (NEF) of 2.9 at 8.2 kHz
      bandwidth for spike recording, and a NEF of 3.2 at 140 Hz bandwidth for EEG
      recording. The amplifier has a measured midband gain of 39.6 dB, frequency
      response from 0.2 Hz to 8.2 kHz, and an input-referred noise of 1.94 muV rms
      while drawing 12.2 muA of current from a 3.3 V supply. The lower and higher
      cutoff frequencies of the bandpass filter are adjustable from 0.2 to 94 Hz and
      140 Hz to 8.2 kHz, respectively. At 10-bit resolution, the ADC has an SNDR of 56
      dB while consuming 76 muW power. Time-modulation feedback in the ADC offers
      programmable digital gain (1-4096) for auto-ranging, further improving the
      dynamic range and linearity of the ADC. Experimental recordings with the system
      show spike signals in rat somatosensory cortex as well as alpha EEG activity in a
      human subject. 

PMID- 20046963
TI  - Dynamics of Microvillus Extension and Tether Formation in Rolling Leukocytes.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin mediates
      leukocyte rolling under conditions of flow. In human neutrophils, a type of
      leukocyte belonging to the innate immune system, PSGL-1 molecules are located on
      the neutrophil's surface ruffles, called microvilli. Each newly formed P-selectin
      PSGL-1 bond can become load bearing, imposing on its microvillus a pulling force
      that deforms the microvillus. Depending on the magnitude of the bond force, a
      microvillus can be extended, or a thin membrane cylinder (a tether) can be formed
      at the tip of the microvillus. Here we propose a Kelvin-Voigt viscoelastic
      material as an improved model for microvillus extension. Using a modified version
      of our Event-Tracking Model of Adhesion (ETMA), we demonstrate how P-selectin
      PSGL-1 load-bearing bonds shape microvillus deformation during neutrophil rolling
      at low shear (wall shear rate of 50 s(-1), P-selectin site density of 150
      molecules MUm(-2)). We also discuss the impact of microvillus deformability on
      neutrophil rolling. We find that the average microvillus extension constitutes
      65% of the total microvillus-tether complex extension, and that the rolling
      neutrophil may never fully rest. A quantitative comparison with the corresponding
      non-deformable microvilli case supports a concept that the ability of the
      microvillus to deform stabilizes cell rolling.

PMID- 20046961
TI  - Integrating costimulatory agonists to optimize immune-based cancer therapies.
AB  - While immunotherapy for cancer has become increasingly popular, clinical benefits
      for such approaches remain limited. This is likely due to tumor-associated immune
      suppression, particularly in the advanced-disease setting. Thus, a major goal of
      novel immunotherapeutic design has become the coordinate reversal of existing
      immune dysfunction and promotion of specific tumoricidal T-cell function.
      Costimulatory members of the TNF-receptor family are important regulators of T
      cell-mediated immunity. Notably, agonist ligation of these receptors restores
      potent antitumor immunity in the tumor-bearing host. Current Phase I/II
      evaluation of TNF-receptor agonists as single-modality therapies will illuminate
      their safety, mechanism(s) of action, and best use in prospective combinational
      immunotherapy approaches capable of yielding superior benefits to cancer
      patients.

PMID- 20046964
TI  - Speaking and Hearing Clearly: Talker and Listener Factors in Speaking Style
      Changes.
AB  - This article provides an overview of the research concerning the nature of the
      distinct, listener-oriented speaking style called 'clear speech' and its effect
      on intelligibility for various listener populations. We review major findings
      that identify talker, listener and signal characteristics that contribute to the
      characteristically high intelligibility of clear speech. Understanding the
      interplay of these factors sheds light on the interaction between higher level
      cognitive and lower-level sensory and perceptual factors that affect language
      processing. Clear speech research is, thus, relevant for both its theoretical
      insights and practical applications. Throughout the review, we highlight open
      questions and promising future directions.

PMID- 20046966
TI  - Antismoking Threat and Efficacy Appeals: Effects on Smoking Cessation Intentions
      for Smokers with Low and High Readiness to Quit.
AB  - This study examined the effects of sequencing different types of antismoking
      threat and efficacy appeals on smoking cessation intentions for smokers with low
      and high levels of readiness to quit. An experiment was done to test predictions
      based on Witte's (1992) Extended Parallel Process Model and research by Cho and
      Salmon (2006). A national probability sample of 555 adult smokers was recruited
      to take part in this study. Results found a positive two-way interaction effect
      between message threat and perceived level of message efficacy on intentions to
      seek help for quitting. A three-way interaction effect was found between message
      threat, perceived level of message efficacy, and readiness to quit on quitting
      intentions. Both threat and efficacy were important for smokers with low
      readiness to quit, whereas efficacy was most important among smokers with high
      readiness to quit. Implications of the results for antismoking campaigns are
      discussed along with limitations and future directions.

PMID- 20046967
TI  - The Legacy Project Intervention to Enhance Meaningful Family Interactions: Case
      Examples.
AB  - Manualized reminiscence and life review therapies are supported as an evidence
      based, effective treatment for depression among older adults, but this
      therapeutic approach is usually individually administered and has rarely been
      applied in palliative care settings. We combined mutual reminiscence and life
      review with engagement in meaningful activity and examined the efficacy of this
      family-based dyadic intervention to decrease caregiving stress and increase
      family communication. Seventeen individuals living with chronic, life-limiting
      illnesses in the community and their family caregivers received three home visits
      with a master's-level interventionist. During these sessions and through
      structured homework activities, the interventionist actively worked with the
      family to construct a personal Legacy Project, usually a scrapbook with photos, a
      cookbook, or audiotaped stories that celebrated the life of the ill individual.
      All participants in the intervention group initiated a Legacy Project and
      reported that Legacy activities improved family communication. Participation in
      Legacy creation also resulted in increased positive emotional experiences in
      patient and caregiver groups. These results are illustrated through careful
      examination of three case studies.

PMID- 20046969
TI  - Parental Monitoring, Personality, and Delinquency: Further Support for a
      Reconceptualization of Monitoring.
AB  - Stattin and Kerr (2000) suggested reconceptualizing "parental monitoring" and
      presented evidence from a Swedish sample that challenged current operational
      definitions. We replicate and extend their findings. Parental knowledge
      ("monitoring") related more strongly to child disclosure than to parental
      solicitation of information in a more ethnically-diverse U. S. sample. We then
      addressed whether adolescents' personalities accounted for the links between
      child disclosure, parental knowledge, and delinquency. Solicitation, knowledge,
      and disclosure generally did not predict delinquency when controlling for
      adolescent personality. Personality contributed significant incremental validity
      to the statistical prediction of delinquency above and beyond solicitation,
      knowledge, and disclosure; the reverse was generally not true. Adolescents'
      personalities largely account for the "parental monitoring"-delinquency
      association, which supports reconceptualizing monitoring.

PMID- 20046970
TI  - THE PATH AND PROMISE OF FATHERHOOD FOR GANG MEMBERS.
AB  - While an increase in research on criminal desistance has occurred in recent
      years, little research has been applied to the gang field. Using qualitative
      interview data, this article examines fatherhood as a potential turning point in
      the lives of 91 gang members in the San Francisco Bay Area. Fatherhood initiated
      important subjective and affective transformations that led to changes in
      outlook, priorities and future orientation. However, these subjective changes
      were not sufficient unless accompanied by two additional features: first, changes
      in the amount of time spent on the streets and, second, an ability to support
      oneself or one's family with legal income. Though fatherhood is no panacea,
      becoming a father did act as an important turning point toward desistance and
      motivator for change for some.

PMID- 20046965
TI  - Monoclonal antibodies in the treatment of pancreatic cancer.
AB  - Human pancreatic cancer is a malignant disease with almost equal incidence and
      mortality. Effective diagnostic and therapeutic strategies are still urgently
      needed to improve its survival rate. With advances in structural and functional
      genomics, recent work has focused on targeted molecular therapy using monoclonal
      antibodies. This review summarizes the target molecules on the tumor cell surface
      and normal tissue stroma, which are related to pancreatic cancer oncogenesis,
      tumor growth or resistance to chemotherapy, as well as molecules involved in
      regulating inflammation and host immunoresponses. Targeted molecules include cell
      surface receptors, such as the EGF receptor, HER2, death receptor 5 and IGF-1
      receptor. Effects of monoclonal antibodies against these target molecules alone
      or in combination with chemotherapy, small-molecule signal transduction
      inhibitors, or radiation therapy are also discussed. Also discussed are the use
      of toxin or radioisotope conjugates, and information relating to the use of these
      targeting agents in pancreatic cancer clinical trials. Although targeted
      molecular therapy with monoclonal antibodies has made some progress in pancreatic
      cancer treatment, especially in preclinical studies, its clinical application to
      improve the survival rate of pancreatic cancer patients requires further
      investigation.

PMID- 20046972
TI  - Quantifying DNA melting transitions using single-molecule force spectroscopy.
AB  - We stretched a DNA molecule using atomic force microscope and quantified the
      mechanical properties associated with B and S forms of double-stranded DNA
      (dsDNA), molten DNA, and single-stranded DNA (ssDNA). We also fit overdamped
      diffusion models to the AFM time series and used these models to extract
      additional kinetic information about the system. Our analysis provides additional
      evidence supporting the view that S-DNA is a stable intermediate encountered
      during dsDNA melting by mechanical force. In addition, we demonstrated that the
      estimated diffusion models can detect dynamical signatures of conformational
      degrees of freedom not directly observed in experiments.

PMID- 20046971
TI  - Environmental Exposure of Aquatic and Terrestrial Biota to Triclosan and
      Triclocarban.
AB  - The synthetic biocides triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) and
      triclocarban (3,4,4'-trichlorocarbanilide) are routinely added to a wide array of
      antimicrobial personal care products and consumer articles. Both compounds can
      persist in the environment and exhibit toxicity toward a number of biological
      receptors. Recent reports of toxicological effects in wildlife, human cell
      cultures, and laboratory animals have heightened the interest in the occurrence
      of these biocide and related toxic effects. The present study aimed to summarize
      published environmental concentrations of biocides and contrast them with
      toxicity threshold values of susceptible organisms. Environmental occurrences and
      toxicity threshold values span more than six orders of magnitude in
      concentration. The highest biocide levels, measured in the mid parts-per-million
      range, were determined to occur in aquatic sediments and in municipal biosolids
      destined for land application. Crustacea and algae were identified as the most
      sensitive species, susceptible to adverse effects from biocide exposures in the
      parts-per-trillion range. An overlap of environmental concentrations and toxicity
      threshold values was noted for these more sensitive organisms, suggesting
      potential adverse ecological effects in aquatic environments. Affirmative
      evidence for this is lacking, however, since studies examining environmental
      occurrences of biocides vis-a-vis the health and diversity of aquatic species
      have not yet been conducted.

PMID- 20046973
TI  - Maternal Sensitivity and the Learning-Promoting Effects of Depressed and Non
      Depressed Mothers' Infant-Directed Speech.
AB  - The hypothesis that aspects of current mother-infant interactions predict an
      infant's response to maternal infant-directed speech (IDS) was tested. Relative
      to infants of non-depressed mothers, those of depressed mothers acquired weaker
      voice-face associations in response to their own mothers' IDS in a conditioned
      attention paradigm, although this was partially attributable to demographic
      differences between the two groups. The extent of fundamental frequency
      modulation (DeltaF(0)) in maternal IDS was smaller for infants of depressed than
      non-depressed mothers, but did not predict infant learning. However, Emotional
      Availability Scale ratings of maternal sensitivity, coded from videotapes of
      mothers and infants engaged in a brief play interaction, were significant
      predictors of infant learning, even after maternal depression, its demographic
      correlates, and antidepressant medication use had been taken into account. These
      findings are consistent with a role for experience-dependent processes in
      determining IDS's effects on infant learning.

PMID- 20046974
TI  - Early Feeding Abilities in Children with Cerebral Palsy: A Parental Report Study.
AB  - PURPOSE: The goals of this study were to 1) describe the feeding skills of young
      children with cerebral palsy (CP); and 2) elucidate the type and severity of
      feeding problems for children with and without oral-motor involvement.  METHOD:
      Parents of 37 children (16 females, 21 males) with CP, who ranged in age from 11
      58 months (mean age = 41 months), completed questionnaires regarding their
      child's past and current feeding abilities. Children were also clinically
      evaluated to determine whether each had evidence of oral-motor involvement. 
      RESULTS: Children with CP and oral-motor involvement had significantly more
      difficulty with self-feeding, increased frequency of coughing and choking,
      increased prevalence of swallowing evaluation and feeding therapy, and were
      introduced to solid food at a later age relative to children with CP who did not
      have oral-motor involvement. Both groups of children were similar in their
      history of tube feeding, bottle feeding, difficulty with solid foods, use of
      adaptive equipment, duration of mealtimes, and presence of choking, coughing, and
      gagging.  CONCLUSIONS: Children with and without oral-motor involvement initially
      presented with similar feeding difficulties. However, feeding problems appeared
      to resolve to a greater extent in children without oral-motor involvement. The
      difficulties identified early in life, for children with oral-motor involvement,
      appeared to persist with development.

PMID- 20046975
TI  - Spatial Linear Mixed Models with Covariate Measurement Errors.
AB  - Spatial data with covariate measurement errors have been commonly observed in
      public health studies. Existing work mainly concentrates on parameter estimation
      using Gibbs sampling, and no work has been conducted to understand and quantify
      the theoretical impact of ignoring measurement error on spatial data analysis in
      the form of the asymptotic biases in regression coefficients and variance
      components when measurement error is ignored. Plausible implementations, from
      frequentist perspectives, of maximum likelihood estimation in spatial covariate
      measurement error models are also elusive. In this paper, we propose a new class
      of linear mixed models for spatial data in the presence of covariate measurement
      errors. We show that the naive estimators of the regression coefficients are
      attenuated while the naive estimators of the variance components are inflated, if
      measurement error is ignored. We further develop a structural modeling approach
      to obtaining the maximum likelihood estimator by accounting for the measurement
      error. We study the large sample properties of the proposed maximum likelihood
      estimator, and propose an EM algorithm to draw inference. All the asymptotic
      properties are shown under the increasing-domain asymptotic framework. We
      illustrate the method by analyzing the Scottish lip cancer data, and evaluate its
      performance through a simulation study, all of which elucidate the importance of
      adjusting for covariate measurement errors.

PMID- 20046976
TI  - Variable Selection for Partially Linear Models with Measurement Errors.
AB  - This article focuses on variable selection for partially linear models when the
      covariates are measured with additive errors. We propose two classes of variable
      selection procedures, penalized least squares and penalized quantile regression,
      using the nonconvex penalized principle. The first procedure corrects the bias in
      the loss function caused by the measurement error by applying the so-called
      correction-for-attenuation approach, whereas the second procedure corrects the
      bias by using orthogonal regression. The sampling properties for the two
      procedures are investigated. The rate of convergence and the asymptotic normality
      of the resulting estimates are established. We further demonstrate that, with
      proper choices of the penalty functions and the regularization parameter, the
      resulting estimates perform asymptotically as well as an oracle procedure (Fan
      and Li 2001). Choice of smoothing parameters is also discussed. Finite sample
      performance of the proposed variable selection procedures is assessed by Monte
      Carlo simulation studies. We further illustrate the proposed procedures by an
      application.

PMID- 20046977
TI  - ESTIMATION IN A SEMI-PARAMETRIC TWO-STAGE RENEWAL REGRESSION MODEL.
AB  - We discuss estimation in a two-stage modulated renewal process designed for
      analysis of paired data on a single individual. We consider a model with
      proportional hazard intensities. U-process methods are used to show consistency
      and asymptotic normality of the parameter estimates.

PMID- 20046978
TI  - Do Older Adults Know Their Spouses' End-of-Life Treatment Preferences?
AB  - When terminally ill patients become mentally incapacitated, the patient's
      surrogate often makes treatment decisions in collaboration with health care
      providers. We examine how surrogates' errors in reporting their spouse's
      preferences are affected by their gender, status as durable power of attorney for
      health care (DPAHC), whether the surrogate and spouse held discussions about end
      of-life preferences, and the spouse's health status. We apply structural equation
      models to data from 2,750 married couples in their mid 60s who participated in
      the 2004 wave of the Wisconsin Longitudinal Study. Surrogates reported their
      spouse's preferences incorrectly 13 and 26 percent of the time in end-of-life
      scenarios involving cognitive impairment and physical pain, respectively.
      Surrogates projected their own preferences onto the spouse. Similar patterns
      emerged regardless of surrogate gender, surrogate status as DPAHC, marital
      discussions about end-of-life, or spousal health status. We discuss implications
      for the process of surrogate decision-making and for future research.

PMID- 20046979
TI  - Identification of emotionally ambiguous interpersonal stimuli among dysphoric and
      nondysphoric individuals.
AB  - This study examined whether dysphoria influences the identification of non
      ambiguous and ambiguous facial expressions of emotion. Dysphoric and non
      dysphoric college students viewed a series of human faces expressing sadness,
      happiness, anger, and fear that were morphed with each other to varying degrees.
      Dysphoric and non-dysphoric individuals identified prototypical emotional
      expressions similarly. However, when viewing ambiguous faces, dysphoric
      individuals were more likely to identify sadness when mixed with happiness than
      non-dysphoric individuals. A similar but less robust pattern was observed for
      facial expressions that combined fear and happiness. No group differences in
      emotion identification were observed for faces that combined sadness and anger or
      fear and anger. Dysphoria appears to enhance the identification of negative
      emotion in others when positive emotion is also present. This tendency may
      contribute to some of the interpersonal difficulties often experienced by
      dysphoric individuals.

PMID- 20046980
TI  - Thermostat artifacts in replica exchange molecular dynamics simulations.
AB  - We explore the effects of thermostats in replica exchange molecular dynamics
      (REMD) simulations. For thermostats that do not produce a canonical ensemble,
      REMD simulations are found to distort the configuration-space distributions. For
      bulk water, we find small deviations of the average potential energies, the
      buildup of tails in the potential energy distributions, and artificial
      correlations between the energies at different temperatures. If a solute is
      present, as in protein folding simulations, its conformational equilibrium can be
      altered. In REMD simulations of a helix-forming peptide with a weak-coupling
      (Berendsen) thermostat, we find that the folded state is overpopulated by about
      10% at low temperatures, and underpopulated at high temperatures. As a
      consequence, the enthalpy of folding deviates by almost 3 kcal/mol from the
      correct value. The reason for this population shift is that non-canonical
      ensembles with narrowed potential energy fluctuations artificially bias toward
      replica exchanges between low-energy folded structures at the high temperature
      and high-energy unfolded structures at the low temperature. We conclude that REMD
      simulations should only be performed in conjunction with thermostats that produce
      a canonical ensemble.

PMID- 20046981
TI  - Personality Disorder in Social Networks: Network Position as a Marker of
      Interpersonal Dysfunction.
AB  - The present study investigated social network position as a marker of
      interpersonal functioning in personality disorders. Participants were groups of
      military recruits (N=809) in 21 training groups. Participants completed self- and
      informant-versions of the Multisource Assessment of Personality Pathology, acting
      as both targets and judges in a round-robin design. Network characteristics were
      associated with both self- and peer-reported personality disorder traits.
      Consistent with DSM-IV descriptors, measures of centrality and degree
      connectivity were positively associated with Narcissistic and Histrionic PDs, and
      negatively associated with Avoidant, Schizoid, and Schizotypal PDs.

PMID- 20046982
TI  - Internal Functionalization and Surface Modification of Vinylsilsesquioxane
      Nanoparticles.
AB  - The interior of 237 nm spherical vinylsilsesquioxane nanoparticles has been
      covalently modified and their surface functionalized under mild conditions to
      yield a novel type of hybrid silsesquioxane nanoparticles. Data obtained from
      thermogravimetric and elemental analysis show that the vinyl groups inside the
      nanoparticles can be easily brominated or hydroborated, leading to the
      nanoparticles containing 59.9 wt% of bromine or 3.6 wt% of boron, respectively.
      Our results demonstrate that the vinyl groups inside the nanoparticles are highly
      accessible, which may lead to the preparation of a host of hybrid organosilica
      nanoparticles with complex structures. We also show that the surface of the
      brominated and boronated nanoparticles is unhindered for further amination.

PMID- 20046984
TI  - Waiting for Brandon: How Readers Respond to Small Mysteries.
AB  - When readers experience narratives they often encounter small mysteries-questions
      that a text raises that are not immediately settled. In our experiments,
      participants read stories that introduced characters by proper names (e.g., "It's
      just that Brandon hasn't called in so long"). Resolved versions of the stories
      specified the functions those characters' assumed in their narrative worlds with
      respect to the other characters (e.g., Brandon was identified as the speaker's
      grandson); unresolved versions of the stories did not immediately provide that
      information. We predicted that characters whose functions were still unresolved
      would remain relatively accessible in the discourse representations. We tested
      that prediction in Experiments 1 and 2 by asking participants to indicate whether
      a name (e.g., Brandon) had appeared in the story. Participants responded most
      swiftly when the characters remained unresolved. In the latter experiments, we
      demonstrated that the presence of an unresolved character disrupted processing of
      information that followed that character's introduction (Experiment 3) but not
      information that preceded that introduction (Experiment 4). These results support
      the general importance of providing a theoretical account of readers' responses
      to narrative mysteries.

PMID- 20046983
TI  - Collecting Duct Renin: A major player in Angiotensin II-dependent Hypertension.
AB  - Recently, the focus of interest on the role of the renin angiotensin system in
      the pathophysiology of hypertension has shifted towards greater emphasis on new
      developments in local renin angiotensin systems in specific tissues. We have
      focused our recent investigations on the role of the intrarenal-intratubular RAS
      in hypertension. All of the components needed for angiotensin II generation are
      present within the various compartments in the kidney. This brief review is
      focused on recent evidence that inappropriate activation of renin in distal
      nephron segments, by acting on angiotensinogen generated in the proximal tubule
      cells and delivered to the distal nephron may contribute to increased distal
      intrarenal angiotensin II formation, sodium retention and development and
      progression of hypertension.

PMID- 20046985
TI  - 2-year-olds use distributional cues to interpret transitivity-alternating verbs.
AB  - Two-year-olds assign appropriate interpretations to verbs presented in two
      English transitivity alternations, the causal and unspecified-object alternations
      (Naigles, 1996). Here we explored how they might do so. Causal and unspecified
      object verbs are syntactically similar. They can be either transitive or
      intransitive, but differ in the semantic roles they assign to the subjects of
      intransitive sentences (undergoer and agent, respectively). To distinguish verbs
      presented in these two alternations, children must detect this difference in role
      assignments. We examined distributional features of the input as one possible
      source of information about this role difference. Experiment 1 showed that in a
      corpus of child-directed speech, causal and unspecified-object verbs differed in
      their patterns of intransitive-subject animacy and lexical overlap between nouns
      in subject and object positions. Experiment 2 tested children's ability to use
      these two distributional cues to infer the meaning of a novel causal or
      unspecified-object verb, by separating the presentation of a novel verb's
      distributional properties from its potential event referents. Children acquired
      useful combinatorial information about the novel verb simply by listening to its
      use in sentences, and later retrieved this information to map the verb to an
      appropriate event.

PMID- 20046986
TI  - Glial response to polyglutamine-mediated stress.
AB  - Neurodegenerative trinucleotide (CAG) repeat disorders are caused by the
      expansion of polyglutamine tracts within the disease proteins. Some of these
      proteins have an unknown function. How does expanded polyglutamine cause target
      neurons to degenerate, is not clear. Recent evidence suggests that intercellular
      miscommunication may contribute to polyglutamine pathogenesis in CAG repeat
      disorders. Polyglutamine induced degeneration of the target neuron can be
      mediated via glia-neuron interactions. Here we hypothesize during
      neurodegenerative process the failure of cell: cell interactions have more severe
      consequences than alterations in intracellular neuron biology. We further believe
      that bidirectional communication between neurons and glia are prerequisite for
      the normal development and function of either cell-type. Understanding
      intercellular signaling mechanisms such as glial trophic factors and their
      receptors, cell adhesion or other well-defined signaling molecules provide
      opportunities for developing potential therapies.

PMID- 20046987
TI  - Biological basis for the co-morbidity between smoking and mood disorders.
AB  - Nicotine dependence is still the major preventable cause of death in the
      developed world, and has strong comorbity with mood disorders including major
      depression. Depressed patients are more likely to smoke cigarettes, and quitting
      can precipitate an episode of depression in some subjects. Interestingly,
      antidepressants, particularly the atypical antidepressant buproprion, are
      therapeutics that can help smokers quit. Despite these observations, the
      underlying biological factors of the relationship between smoking and depression
      remain unclear. Results from clinical and pre-clinical studies have seemed
      somewhat paradoxical because heightened cholinergic activity can induce
      depression while both nicotine and nicotinic antagonists can be antidepressant
      like. These observations can be reconciled by considering that high affinity
      nicotinic receptors in the brain can be desensitized by chronic nicotine use,
      leading to blunted cholinergic activity. Based on this hypothesis, nicotinic
      antagonists have recently been tested as treatments for depression in human
      subjects, particularly as adjunct therapy along with classical antidepressants.
      These data suggest that the relationship between smoking and depression may be
      partially explained by the fact that depressed patients smoke in an effort to
      self-medicate depressive symptoms by desensitizing their nicotinic receptors.
      This possibility suggests new avenues for treatment of both nicotine dependence
      and depressive disorders.

PMID- 20046988
TI  - Effect of PCBs on the lactational transfer of methyl mercury in mice: PBPK
      modeling.
AB  - MeHg and PCB exposure to lactating mice were analyzed and a physiologically-based
      pharmacokinetic (PBPK) model was developed to describe the lactational transfer
      of MeHg in mice. The influence of albumin on the lactational transfer of MeHg was
      incorporated into the PBPK model. Experimental results with lactating mice and
      their pups showed that co-exposure with PCB congeners increased the lactational
      transfer of MeHg to the pups, which was associated with the rise of albumin
      levels in maternal blood. Observed results were matched with PBPK model
      simulations conducted under the assumptions that (1) MeHg bound to plasma albumin
      is transferred to maternal milk, and (2) PCB congeners may increase the
      lactational transfer of MeHg by escalating albumin levels in maternal blood.
      Further refinement of PBPK model quantitatively described the pharmacokinetic
      changes of MeHg by co-exposure with PCBs in pup's tissues.

PMID- 20046989
TI  - Direct Conversion of Aldehydes and Ketones to Allylic Halides by a NbX(5-)[3,3]
      Rearrangement.
AB  - Sequential addition of vinylmagnesium bromide and NbCl(5), or NbBr(5), to a
      series of aldehydes and ketones directly provides homologated, allylic halides.
      Transposition of the intermediate vinyl alkoxide is envisaged through a metalla
      halo-[3,3] rearrangement with concomitant delivery of the halogen to the terminal
      carbon. The [3,3] rearrangement is equally effective for the conversion of a
      propargyllic alcohol to the corresponding allenyl bromide.

PMID- 20046990
TI  - Differences in female and male involvement in lethal violence in Russia.
AB  - Relatively little is known of the distributions of homicide event characteristics
      in non-Western nations in which women relative to men are involved. This article
      utilizes unique homicide narratives drawn from Russian court and police records
      to compare homicide victim, offender, and event characteristics by sex of victim
      and separately by sex of offender. Results from logistic regression show that
      homicides in which a female was the victim or offender were more likely to occur
      between intimates and to occur in the home, whereas homicides involving males
      were more likely to occur in a public place, to be alcohol-related, to involve a
      firearm, and to involve a victim and offender who did not know each other well.
      These results not only present an important first glimpse at women as homicide
      victims and offenders in Russia specifically, but also provide a point of
      comparison with findings from similar analyses undertaken in the West, and
      present further initial observations upon which to construct a cohesive theory
      about female involvement in serious violent events.

PMID- 20046991
TI  - Aziridines as intermediates in diversity-oriented syntheses of alkaloids.
AB  - The efficient synthesis of small molecules that collectively comprise optimal
      small-molecule screening collections is an important goal. With this in mind, we
      have used N-alkyl aziridines in a regio- and stereochemically controlled
      synthesis of polycyclic heterocycles based on nucleophilic ring opening and
      subsequent intramolecular cyclization.

PMID- 20046992
TI  - Comparison of Research Designs for Two Controlled Trials of Mass Media
      Interventions.
AB  - This paper compares two controlled trials of mass media interventions, factors
      influencing their designs, and design lessons learned from these experiences.
      Mass media evaluations based on a scientific research model are motivated by gaps
      in knowledge. The results of such research are intended to serve the needs of
      consensus development processes through which confident recommendations can be
      made for intervention strategies that should be more widely applied. For these
      purposes, the scientific research context emphasizes internal validity of
      evaluation design, such as controlled experiments. This paper describes two such
      trials, implemented at different times with differing social contexts for youth
      cigarette smoking, smoking prevention research evidence bases, and tobacco
      control environments. Common and unique features of the two trials are reviewed,
      and observations are noted about the conditions under which controlled trials of
      mass media interventions might be warranted.

PMID- 20046993
TI  - Metallic Nanostructures as Localized Plasmon Resonance Enhanced Scattering Probes
      for Multiplex Dark Field Targeted Imaging of Cancer Cells.
AB  - In this paper, we report the use of bioconjugated gold nanorods and silver
      nanoparticles as targeted localized surface plasmon resonance enhanced scattering
      probes for dark field multiplex and transmission electron microscopy (TEM)
      imaging of pancreatic cancer cells. We take advantage of the spectrally widely
      separated localized plasmon resonance of the gold nanorods and silver
      nanoparticles which produce wavelength selective plasmon resonance scattering to
      allow multiplex imaging with high contrast. By functionalizing the surfaces,
      aqueous dispersions of bioconjugated gold nanorods and silver nanoparticles are
      prepared. We demonstrate receptor-mediated delivery of bioconjugated gold
      nanorods and silver nanoparticles simultaneously into pancreatic cancer cells,
      using multiplexed dark field microscopy technique. We also show that the
      bioconjugated metallic nanostructures can be used for high contrast TEM imaging
      as well.

PMID- 20046994
TI  - Role of NKT cells in anterior chamber-associated immune deviation.
AB  - Cells in the eye have a limited capacity for regeneration and, as such, immune
      mediated inflammation can lead to blindness. The eye is designed to quench immune
      mediated inflammation - a condition known as immune privilege. An important
      component of immune privilege is the dynamic immunoregulatory process termed
      anterior chamber-associated immune deviation (ACAID), which is initiated when
      antigens enter the eye. ACAID suppresses the initiation of antigen-specific
      inflammation in the eye and the effector stages of immune reactions. Four organ
      systems are crucial for the induction of ACAID: the eye, thymus, spleen and
      sympathetic nervous system. Multiple cell populations contribute to ACAID, with
      natural killer T cells playing a crucial role in the thymic and splenic phases of
      ACAID. Interactions between natural killer T cells and multiple cell populations
      in the spleen culminate in the tight regulation of immune-mediated inflammation
      in the eye and the preservation of vision.

PMID- 20046996
TI  - Satisfaction with Counseling among Black Males in Transition from the Foster Care
      System.
AB  - Using the Multidimensional Adolescent Satisfaction Scale (Garland, Saltzman, &
      Aarons, 2000), satisfaction with counseling and associated variables were
      examined among Black males (n = 47) transitioning from the foster care system.
      Potential associated variables assessed were foster care custody status,
      counseling status, diagnosis of major depression and disruptive behavior disorder
      based DSM-IV criteria, history of placement in congregate care settings,
      attitudes toward mental health services, stigma beliefs, and masculine norms.
      Results from simultaneous multiple regression analysis showed that attitudes
      toward mental health services contributed significantly to satisfaction with
      counseling. Specifically, Black males who expressed more positive attitudes
      toward mental health services in terms of confidence in mental health
      professionals and the therapeutic process reported greater satisfaction.
      Implications and future research directions are discussed.

PMID- 20046995
TI  - Validating CHARMM parameters and exploring charge distribution rules in structure
      based drug design.
AB  - Using an extensive series of TIBO compounds that are non-nucleoside inhibitors of
      HIV-1 reverse transcriptase, we have systematically evaluated the quality of
      recently developed ligand parameters that are consistent with the CHARMM22 force
      field. Thermodynamic integration simulations for 44 pairs of TIBO compounds
      achieve a high level of success with an overall average unsigned error (AUE) in
      the relative binding affinities of 1.3 kcal/mol; however, the accuracy is
      strongly dependent on the size differential between the substituents sampled as
      well as the class of functional group. Low errors are observed among the alkyl,
      allyl, aldehyde, nitrile, trifluorinated methyl, and halide TIBO derivatives and
      large systematic errors among thioether derivatives. We have also investigated
      how different charge assignment schemes for small molecules impact the quality of
      computed binding affinities for a subset of this series. This study demonstrates
      the advantage of using model compounds to derive physically meaningful charge
      distributions and bond-charge increments for rapidly expanding fragment libraries
      for drug development applications. Specifically, in the absence of a bond-charge
      increment for a given pair of atom types, the strategy of adopting CHELPG charges
      from localized regions of model compounds provides reliable results when modeling
      with the CHARMM force field.

PMID- 20046997
TI  - Quantitative Determination of the Regioselectivity of Nucleophilic Addition to
      eta-Propargyl Rhenium Complexes and Direct Observation of an Equilibrium Between
      eta-Propargyl Rhenium Complexes and Rhenacyclobutenes.
AB  - PMe(3) adds selectively to the central carbon of the eta(3)- propargyl complex
      [C(5)Me(5)(CO)(2)Re(eta(3)-CH(2)C=CCMe(3))][BF(4)] (1-t-Bu) to form the
      metallacyclobutene [C(5)Me(5)(CO)(2)Re(CH(2)C(PMe(3))=CCMe(3))][BF(4)] (7). The
      rate of rearrangement of the metallacyclobutene 7 to eta(2)-alkyne complex
      [C(5)Me(5)(CO)(2)Re(eta(2)-Me(3)PCH(2)C=CCMe(3))][BF(4)] (8) is is independent of
      phosphine concentration, consistent with a dissociative mechanism proceeding via
      eta(3)-propargyl complex 1-t-Bu. The rate of this rearrangement is 480 times
      slower than the rate of exchange of PMe(3) with the labeled metallacyclobutene 7
      d(9). This rate ratio provides an indirect measurement of the regioselectivity
      for addition of PMe(3) to the central carbon of eta(3)-propargyl complex 1-t-Bu
      to give 7 compared to addition to a terminal carbon to give 8. The addition of
      PPh(3) to 1-t-Bu gives the metallacyclobutene
      [C(5)Me(5)(CO)(2)Re(CH(2)C(PPh(3))=CCMe(3))][BF(4)] (11). Low temperature (1)H
      NMR spectra provide evidence for an equilibrium between metallacyclobutene 11 and
      eta(3)-propargyl complex 1-t-Bu (K(eq) ~ 44 M(-1) at -46  degrees C and DeltaG
      degrees  (0  degrees C) = -1.2 +/- 0.2 kcal mol(-1)).

PMID- 20046998
TI  - GOOD HEALTH AND THE BRIDGING OF STRUCTURAL HOLES.
AB  - Bridges that span structural holes are often explained in terms of the
      entrepreneurial personalities or rational motivations of brokers, or structural
      processes that lead to the intersection of social foci. I argue that the
      existence and use of bridges in interpersonal networks also depends on
      individuals' health. Poor health may make it more difficult to withstand the
      pressures and to execute some of the common tasks associated with bridging (e.g.,
      brokerage). I examine this possibility using egocentric network data on over
      2,500 older adults drawn from the recent National Social Life, Health, and Aging
      Project (NSHAP). Multivariate regression analyses show that both cognitive and
      functional health are significantly positively associated with bridging, net of
      sociodemographic and life-course controls. The relationship between functional
      (kinesthetic) health and bridging appears to be partially mediated by network
      composition, as older adults who have poorer functional health also tend to have
      networks that are richer in strong ties. Several potential mediation mechanisms
      are discussed. Cognitive function remains significantly associated with bridging
      net of network composition, suggesting that the inherent challenges of
      maintaining bridging positions may be more difficult to cope with for those who
      have cognitive impairments than for those who have functional impairments such as
      limited mobility. An alternative explanation is that cognitively impaired
      individuals have more difficulty recognizing (and thus strategically using)
      bridges in their networks. Theoretical implications and possibilities for future
      research are discussed.

PMID- 20046999
TI  - Do gender differences in the role of dysfunctional attitudes in depressive
      symptoms depend on depression history?
AB  - Gender differences in the moderating role of dysfunctional attitudes in the
      relationship between life stress and depressive symptoms were examined with and
      without controlling for the presence of lifetime history of depression. When
      lifetime history of depression was controlled, dysfunctional attitudes played a
      moderating role in the relationship between life stress and depressive symptoms
      for both men and women. However, when lifetime history of depression was not
      controlled, dysfunctional attitudes moderated the relationship of life stress and
      depressive symptoms for women only. The results suggest gender differences in the
      moderating role of dysfunctional attitudes may be contingent on lifetime history
      of depression and that past depression may exert differing effects for men and
      women.

PMID- 20047000
TI  - The role of african american ethnicity and metabolism in sentinel polychlorinated
      biphenyl congener serum levels.
AB  - Polychlorinated biphenyls (PCBs) are environmental contaminants found in the
      serum of human populations across the globe. A small set of sentinel PCB
      congeners (IUPAC# 101, 118, 138, 153, and 180) commonly sought in human serum are
      often used as markers of exposure. The Chicago Great Lakes cohort of pregnant
      African American women was developed to study organochlorine exposure through
      Great Lakes resources in a pregnant African American population and their
      children. Comparison of PCB serum concentrations in women reporting mixed
      race/ethnicity within the cohort shows significant elevations of serum PCB 101
      and 118 in women reporting exclusive African American ancestry.Incubations were
      performed using pooled human liver microsomes followed by individual recombinant
      human CYP isoform microsomes to identify whether the other sentinel congeners are
      metabolized by human CYP 450. In human liver microsome metabolism experiments
      with the sentinel PCB congeners (IUPAC# 101, 118, 138, 153, and 180), only PCB
      101 metabolism produced an identifiable metabolite. However, a significant loss
      of parent compound was observed for PCB 118 incubations with human liver
      microsomes. The loss of PCB 101 and PCB 118 in microsome experiments indicates
      they are likely metabolized in human liver. Therefore, CYP 450 mediated metabolic
      differences may contribute to differences in serum concentrations by
      race/ethnicity.PCB metabolism has an important impact on toxicity. PCB
      metabolites have been shown to differ significantly in toxicity profiles relative
      to parent compounds. Biomonitoring studies of PCB serum levels have correlated
      with toxicity for the metabolizeable congeners such as PCB 101 and PCB 118.
      However, measureable amounts of metabolizeable parent congeners such as PCB 101
      may not be detectable in the serum of study participants. Because PCB 118 is
      metabolized, but is also readily found in human serum, it may be a better marker
      of metabolism related PCB toxicity. Human specific PCB metabolism is difficult to
      characterize but has important pathophysiological ramifications and deserves
      further study.

PMID- 20047001
TI  - Self-Esteem Depends on the Beholder: Effects of a Subtle Social Value Cue.
AB  - The idea that self-esteem functions as a gauge or "sociometer" of social value
      (Leary & Baumeister, 2000) is supported by research on direct social feedback. To
      examine if the sociometer model is relevant to more subtle social value cues, the
      implicit self-esteem of women was assessed a week after an interaction with an
      experimenter. Consistent with the sociometer model, Week 2 self-esteem depended
      on a subtle social value cue encountered during Week 1. When the Week 1
      experimenter wore a t-shirt celebrating larger bodies (i.e., "everyBODY is
      beautiful"), heavier women had higher self-esteem than lighter women in Week 2.
      As hypothesized, this effect was relationship-specific, occurring only when the
      same experimenter administered Week 1 and 2 sessions.

PMID- 20047002
TI  - Simulating Brain Tumor Heterogeneity with a Multiscale Agent-Based Model: Linking
      Molecular Signatures, Phenotypes and Expansion Rate.
AB  - We have extended our previously developed 3D multi-scale agent-based brain tumor
      model to simulate cancer heterogeneity and to analyze its impact across the
      scales of interest. While our algorithm continues to employ an epidermal growth
      factor receptor (EGFR) gene-protein interaction network to determine the cells'
      phenotype, it now adds an implicit treatment of tumor cell adhesion related to
      the model's biochemical microenvironment. We simulate a simplified tumor
      progression pathway that leads to the emergence of five distinct glioma cell
      clones with different EGFR density and cell 'search precisions'. The in silico
      results show that microscopic tumor heterogeneity can impact the tumor system's
      multicellular growth patterns. Our findings further confirm that EGFR density
      results in the more aggressive clonal populations switching earlier from
      proliferation-dominated to a more migratory phenotype. Moreover, analyzing the
      dynamic molecular profile that triggers the phenotypic switch between
      proliferation and migration, our in silico oncogenomics data display spatial and
      temporal diversity in documenting the regional impact of tumorigenesis, and thus
      support the added value of multi-site and repeated assessments in vitro and in
      vivo. Potential implications from this in silico work for experimental and
      computational studies are discussed.

PMID- 20047003
TI  - Drop-the-Losers Design: Binomial Case.
AB  - Drop-the-losers designs were introduced for normal distributions as a method of
      combining phase II and III clinical trials together under a single protocol with
      the purpose of more rapidly evaluating drugs by eliminating as much as possible
      the delays that typically occur between the two phases of clinical development.
      In the design, the sponsor would administer k treatments along with a control in
      the first stage. During a brief interim period, efficacy data would be used to
      select the best treatment (with a rule to deal with ties) for further evaluation
      against the control in a second stage. At the end of the study, data from both
      stages would be used to draw inferences about the selected treatment relative to
      the control with adjustments made for selection in between the two stages.
      Because the inferences are model based, exact confidence intervals can be
      determined for the parameter of interest. In the present case, the parameter of
      concern is the probability of a beneficial response that is dichotomous in
      nature.

PMID- 20047004
TI  - Synthesis of [F]fallypride in a micro-reactor: rapid optimization and multiple
      production in small doses for micro-PET studies.
AB  - A commercial coiled-tube micro-reactor (NanoTek; Advion) was used as a convenient
      platform for the synthesis of [(18)F]fallypride in small doses (0.5-1.5 mCi) for
      micro-PET studies of brain dopamine subtype-2 receptors in rodents. Each
      radiosynthesis used low amounts (20-40 mug; 39-77 nmol) of tosylate precursor and
      [(18)F]fluoride ion (0.5-2.5 mCi). Optimization of the labeling reaction in the
      apparatus, with respect to the effects of precursor amount, reaction temperature,
      flow rate and [(18)F]fluoride ion to precursor ratio, was achieved rapidly and
      the decay-corrected radiochemical yield of [(18)F]fallypride (up to 88%) was
      reproducible. The low amounts of material used in each radiosynthesis allowed
      crude [(18)F]fallypride to be purified rapidly on an analytical-size reverse
      phase HPLC column, preceding formulation for intravenous injection. Scale-up of
      the reaction was easily achieved by continuously infusing reagent precursor
      solutions to obtain [(18)F]fallypride in much greater quantity.

PMID- 20047006
TI  - An Effective Hamiltonian Molecular Orbital-Valence Bond (MOVB) Approach for
      Chemical Reactions Applied to the Nucleophilic Substitution Reaction of
      Hydrosulfide Ion and Chloromethane.
AB  - An effective Hamiltonian mixed molecular orbital and valence bond (EH-MOVB)
      method is described to obtain an accurate potential energy surface for chemical
      reactions. Building upon previous results on the construction of diabatic and
      adiabatic potential surfaces using ab initio MOVB theory, we introduce a diabatic
      coupling scaling factor to uniformly scale the ab initio off-diagonal matrix
      element H(12) such that the computed energy of reaction from the EH-MOVB method
      is in agreement with the target value. The scaling factor is very close to unity,
      resulting in minimal alteration of the potential energy surface of the original
      MOVB model. Furthermore, the relative energy between the reactant and product
      diabatic states in the EH-MOVB method can be improved to match the experimental
      energy of reaction. A key ingredient in the EH-MOVB theory is that the off
      diagonal matrix elements are functions of all degrees of freedom of the system
      and the overlap matrix is explicitly evaluated. The EH-MOVB method has been
      applied to the nucleophilic substitution reaction between hydrosulfide and
      chloromethane to illustrate the methodology and the results were matched to
      reproduce the results from ab initio valence bond self-consistent valence bond
      (VBSCF) calculations. The diabatic coupling (the off-diagonal matrix element in
      the generalized secular equation) has small variations along the minimum energy
      reaction path in the EH-MOVB model, whereas it shows a maximum value at the
      transition state and has nearly zero values in the regions of the ion-dipole
      complexes from VBSCF calculations. The difference in the diabatic coupling
      stabilization is attributed to the large overlap integral in the computationally
      efficient MOVB method.

PMID- 20047005
TI  - Perspective on Diabatic Models of Chemical Reactivity as Illustrated by the Gas
      Phase S(N)2 Reaction of Acetate Ion with 1,2-Dichloroethane.
AB  - Diabatic models are widely employed for studying chemical reactivity in condensed
      phases and enzymes, but there has been little discussion of the pros and cons of
      various diabatic representations for this purpose. Here we discuss and contrast
      six different schemes for computing diabatic potentials for a charge
      rearrangement reaction. They include (i) the variational diabatic configurations
      (VDC) constructed by variationally optimizing individual valence bond structures
      and (ii) the consistent diabatic configurations (CDC) obtained by variationally
      optimizing the ground-state adiabatic energy, both in the nonorthogonal molecular
      orbital valence bond (MOVB) method, along with the orthogonalized (iii) VDC-MOVB
      and (iv) CDC-MOVB models. In addition, we consider (v) the fourfold way (based on
      diabatic molecular orbitals and configuration uniformity), and (vi) empirical
      valence bond (EVB) theory. To make the considerations concrete, we calculate
      diabatic electronic states and diabatic potential energies along the reaction
      path that connects the reactant and the product ion-molecule complexes of the gas
      phase bimolecular nucleophilic substitution (S(N)2) reaction of 1,2-dichloethane
      (DCE) with acetate ion, which is a model reaction corresponding to the reaction
      catalyzed by haloalkane dehalogenase. We utilize ab initio block-localized
      molecular orbital theory to construct the MOVB diabatic states and ab initio
      multi-configuration quasidegenerate perturbation theory to construct the fourfold
      way diabatic states; the latter are calculated at reaction path geometries
      obtained with the M06-2X density functional. The EVB diabatic states are computed
      with parameters taken from the literature. The MOVB and fourfold-way adiabatic
      and diabatic potential energy profiles along the reaction path are in qualitative
      but not quantitative agreement with each other. In order to validate that these
      wave-function-based diabatic states are qualitatively correct, we show that the
      reaction energy and barrier for the adiabatic ground state, obtained with these
      methods, agree reasonably well with the results of high-level calculations using
      the composite G3SX and G3SX(MP3) methods and the BMC-CCSD multi-coefficient
      correlation method. However, a comparison of the EVB gas-phase adiabatic ground
      state reaction path with those obtained from MOVB and with the fourfold way
      reveals that the EVB reaction path geometries show a systematic shift towards the
      products region, and that the EVB lowest-energy path has a much lower barrier.
      The free energies of solvation and activation energy in water reported from
      dynamical calculations based on EVB also imply a low activation barrier in the
      gas phase. In addition, calculations of the free energy of solvation using the
      recently proposed SM8 continuum solvation model with CM4M partial atomic charges
      lead to an activation barrier in reasonable agreement with experiment only when
      the geometries and the gas-phase barrier are those obtained from electronic
      structure calculations, i.e., methods i-v. These comparisons show the danger of
      basing the diabatic states on molecular mechanics without the explicit
      calculation of electronic wave functions. Furthermore, comparison of schemes i-v
      with one another shows that significantly different quantitative results can be
      obtained by using different methods for extracting diabatic states from wave
      function calculations, and it is important for each user to justify the choice of
      diabatization method in the context of its intended use.

PMID- 20047007
TI  - Rules Versus Evidence in Memory and Non-Memory Decision-Making.
AB  - Recent research using functional magnetic resonance imaging has revealed that
      memory retrieval often places considerable demands on prefrontal cortex (PFC), a
      region known to underpin complex decision-making. Regional dissociations within
      PFC suggest that memory retrieval recruits several decision processes shared with
      complex decision making in non-memory domains. Here we briefly review data
      highlighting the role of dorsolateral prefrontal cortex (dlPFC) during memory and
      non-memory judgments, which suggest that dlPFC is sensitive to decision
      complexity during memory retrieval. As decision complexity increases, decision
      makers may be more susceptible to stress and/or fatigue with consequent failures
      of memory judgment.

PMID- 20047008
TI  - Quantifying relationships between selected work-related risk factors and back
      pain: a systematic review of objective biomechanical measures and cost-related
      health outcomes.
AB  - The objective of this investigation was to use published literature to
      demonstrate that specific changes in workplace biomechanical exposure levels can
      predict reductions in back injuries. A systematic literature review was conducted
      to identify epidemiologic studies which could be used to quantify relationships
      between several well-recognized biomechanical measures of back stress and
      economically relevant outcome measures. Eighteen publications, describing 15
      research studies, which fulfilled search criteria were found. Quantitative
      associations were observed between back injuries and measures of spinal
      compression, lifting, lifting ratios, postures, and combinations thereof. Results
      were intended to provide safety practitioners with information that could be
      applied to their own work situations to estimate costs and benefits of ergonomic
      intervention strategies before they are implemented.

PMID- 20047009
TI  - Synthesis of the Chlorofusin Cyclic Peptide.
AB  - An efficient and convergent solution-phase synthesis of the cyclic peptide of the
      natural product chlorofusin, a reported inhibitor of the MDM2-p53 interaction, is
      detailed.

PMID- 20047010
TI  - Dipolar Second-Order Nonlinear Optical Chromophores Containing Ferrocene,
      Octamethylferrocene, and Ruthenocene Donors and Strong pi-Acceptors: Crystal
      Structures and Comparison of pi-Donor Strengths.
AB  - Crystal structures have been determined for six dipolar polyene chromophores with
      metallocenyl - ferrocenyl (Fc), octamethylferrocenyl (Fc"), or ruthenocenyl (Rc) 
      donors and strong heterocyclic acceptors based on 1,3-diethyl-2-thiobarbituric
      acid or 3-dicyanomethylidene-2,3-dihydrobenzothiophene-1,1-dioxide. In each case,
      crystals were found to belong to centrosymmetric space groups. For one example,
      polymer-induced heteronucleation revealed the existence of two additional
      polymorphs, which were inactive in second-harmonic generation, suggesting that
      they were also centrosymmetric. The bond-length alternations between the formally
      double and single bonds of the polyene bridges are reduced compared to simple
      polyenes, indicating significant contribution from charge-separated resonance
      structures, although the metallocenes are not significantly distorted towards the
      [(eta(6)-fulvene)(eta(5)-cyclopentadienyl)metal(II)](+) extreme. DFT geometries
      are in excellent agreement with those determined crystallographically; while the
      pi-donor strengths of the three metallocenyl groups are insufficiently different
      to result in detectable differences in the crystallographic bond-length
      alternations, the DFT geometries, as well as DFT-calculations of partial charges
      for atoms, suggest that pi-donor strength decreases in the order Fc" ? Fc > Rc.
      NMR, IR and electrochemical evidence also suggests that octamethylferrocenyl is
      the stronger pi-donor, exhibiting similar pi-donor strength to a p
      (dialkylamino)phenyl group, while ferrocenyl and ruthenocenyl show very similar
      pi-donor strengths to one another in chromophores of this type.

PMID- 20047012
TI  - Individual, Household, and Community U.S. Migration Experience and Infant
      Mortality in Rural and Urban Mexico.
AB  - This study explores rural and urban differences in the relationship between U.S.
      migration experience measured at the individual, household, and community levels
      and individual-level infant mortality outcomes in a national sample of recent
      births in Mexico. Using 2000 Mexican Census data and multi-level regression
      models, we find that women's own U.S. migration experience is associated with
      lower odds of infant mortality in both rural and urban Mexico, possibly
      reflecting a process of healthy migrant selectivity. Household migration has
      mixed blessings for infant health in rural places: remittances are beneficial for
      infant survival, but recent out-migration is disruptive. Recent community-level
      migration experience is not significantly associated with infant mortality
      overall, although in rural places, there is some evidence that higher levels of
      community migration are associated with lower infant mortality. Household- and
      community-level migration have no relationship with infant mortality in urban
      places. Thus, international migration is associated with infant outcomes in
      Mexico in fairly complex ways, and the relationships are expressed most
      profoundly in rural areas of Mexico.

PMID- 20047011
TI  - The tumor proteasome as a novel target for gold(III) complexes: implications for
      breast cancer therapy.
AB  - Although cisplatin plays a vital role in the treatment of several types of human
      cancer, its wide use is limited by the development of drug resistance and
      associated toxic side effects. Gold and gold complexes have been used to treat a
      wide range of ailments for many centuries. In recent years, the use of gold(III)
      complexes as an alternative to cisplatin treatment was proposed due to the
      similarities of gold and platinum. Gold(III) is isoelectronic with platinum(II)
      and gold(III) complexes have the same square-planar geometries as platinum(II)
      complexes, such as cisplatin. Although it was originally thought that gold(III)
      complexes might have the same molecular target as cisplatin, several lines of
      data indicated that proteins, rather than DNA, are targeted by gold complexes. We
      have recently evaluated cytotoxic and anti-cancer effects of several gold(III)
      dithiocarbamates against human breast cancer cells in vitro and in vivo. We have
      identified the tumor proteasome as an important target for gold(III) complexes
      and have shown that proteasome inhibition by gold(III) complexes is associated
      with apoptosis induction in breast cancer cells in vitro and in vivo.
      Furthermore, treatment of human breast tumor-bearing nude mice with a gold(III)
      dithiocarbamate complex was associated with tumor growth inhibition, supporting
      the significance of its potential development for breast cancer treatment.

PMID- 20047013
TI  - Who Knows Best? Preschoolers Sometimes Prefer Child Informants Over Adult
      Informants.
AB  - Do preschoolers think adults know more about everything than children? Or do they
      recognize that there are some things that children might know more about than
      adults? Three-, four-, and five-year-olds (N = 65) were asked to decide whether
      an adult or child informant would better be able to answer a variety of questions
      about the nutritional value of foods and about toys. Children at all ages chose
      to direct the food questions to the adult and the toy questions to the child.
      Thus, there are some kinds of information for which preschoolers expect that a
      child would be a better informant than an adult.

PMID- 20047014
TI  - Discoveries from the Abyss: The Abyssomicins and Their Total Synthesis.
AB  - Abyssomicin C is a recently discovered antibiotic with promising antibacterial
      activity, high structural complexity, and a novel mechanism of action. We give an
      account of our abyssomicin campaign and some of the discoveries that were borne
      of our total synthesis efforts, including a new Lewis acid-templated Diels-Alder
      reaction, the previously undescribed atrop-abyssomicin C, a facile Bronsted acid
      catalyzed isomerization of abyssomicin C, and clarification of the likely
      biosynthetic origin of abyssomicin D.

PMID- 20047016
TI  - Internalized Homophobia and Relationship Quality among Lesbians, Gay Men, and
      Bisexuals.
AB  - We examined the associations between internalized homophobia, outness, community
      connectedness, depressive symptoms, and relationship quality among a diverse
      community sample of 396 lesbian, gay, and bisexual (LGB) individuals. Structural
      equation models showed that internalized homophobia was associated with greater
      relationship problems both generally and among coupled participants independent
      of outness and community connectedness. Depressive symptoms mediated the
      association between internalized homophobia and relationship problems. This study
      improves current understandings of the association between internalized
      homophobia and relationship quality by distinguishing between the effects of the
      core construct of internalized homophobia and its correlates and outcomes. The
      findings are useful for counselors interested in interventions and treatment
      approaches to help LGB individuals cope with internalized homophobia and
      relationship problems.

PMID- 20047015
TI  - Endocrine disrupting chemicals in indoor and outdoor air.
AB  - The past 50 years have seen rapid development of new building materials,
      furnishings, and consumer products and a corresponding explosion in new chemicals
      in the built environment. While exposure levels are largely undocumented, they
      are likely to have increased as a wider variety of chemicals came into use,
      people began spending more time indoors, and air exchange rates decreased to
      improve energy efficiency. As a result of weak regulatory requirements for
      chemical safety testing, only limited toxicity data are available for these
      chemicals. Over the past 15 years, some chemical classes commonly used in
      building materials, furnishings, and consumer products have been shown to be
      endocrine disrupting chemicals-that is they interfere with the action of
      endogenous hormones. These include PCBs, used in electrical equipment, caulking,
      paints and surface coatings; chlorinated and brominated flame retardants, used in
      electronics, furniture, and textiles; pesticides, used to control insects, weeds,
      and other pests in agriculture, lawn maintenance, and the built environment;
      phthalates, used in vinyl, plastics, fragrances, and other products;
      alkylphenols, used in detergents, pesticide formulations, and polystyrene
      plastics; and parabens, used to preserve products like lotions and sunscreens.
      This paper summarizes reported indoor and outdoor air concentrations, chemical
      use and sources, and toxicity data for each of these chemical classes. While
      industrial and transportation-related pollutants have been shown to migrate
      indoors from outdoor sources, it is expected that indoor sources predominate for
      these consumer product chemicals; and some studies have identified indoor sources
      as the predominant factor influencing outdoor ambient air concentrations in
      densely populated areas. Mechanisms of action, adverse effects, and dose-response
      relationships for many of these chemicals are poorly understood and no systematic
      screening of common chemicals for endocrine disrupting effects is currently
      underway, so questions remain as to the health impacts of these exposures.

PMID- 20047017
TI  - Preclinical evaluation of a monoclonal antibody (3C6) specific for prostate
      specific membrane antigen.
AB  - Better tumor markers are needed for early diagnosis and staging of prostate
      cancer, and for monitoring therapeutic response than the currently used prostate
      specific antigen (PSA). Prostate specific membrane antigen (PSMA) is highly
      expressed on the surface of prostatic epithelial cells making it a good target
      for prostate cancer. In this study, mAb 3C6, specific for the extracellular
      epitope of PSMA, was evaluated both in vitro and in vivo for PSMA-targeting.
      Immunoreactivity and specificity of mAb 3C6 was evaluated by flow cytometry using
      prostate cell lines expressing PSMA such as LNCaP and 22Rv1 and a cell line,
      DU145, that expresses very little PSMA. 3C6 was conjugated with the acyclic CHX
      A" DTPA chelate, radiolabeled with (111)In, and its in vitro and in vivo
      properties were assessed. The biodistribution of the radioimmunoconjugate
      evaluated in athymic mice bearing xenografts of three human prostate carcinoma
      cell lines shows high uptake after 72 hr in LNCaP tumors (%ID/g 22.93 +/- 6.32)
      and 22Rv1 (%ID/g 10.44 +/- 2.32) in contrast to low uptake by the DU145 tumors
      (%ID/g 4.27 +/- 0.37). Planar gamma-scintigraphic images obtained for xenografted
      tumor bearing mice demonstrated targeting for PSMA positive tumors suggesting
      possible applications in imaging and for targeted radiation therapy.

PMID- 20047018
TI  - A Longitudinal Examination of Physiological Regulation in Cocaine-Exposed Infants
      Across the First 7 Months of Life.
AB  - This study examined the association between prenatal exposure to cocaine and
      physiological regulation across the first 7 months of age. Measures of
      respiratory sinus arrhythmia (RSA) were obtained from 169 (82 cocaine-exposed and
      87 nonexposed) infants during baseline periods at 1 month and 7 months of age and
      during tasks designed to elicit positive and negative affect at 7 months of age.
      After controlling for maternal age, gestational age, and obstetrical risk,
      structural equation modeling indicated that the association between prenatal
      exposure to cocaine and baseline RSA at 7 months of age was direct even in the
      presence of an indirect effect through baseline RSA at 1 month of age. There were
      no indirect effects through maternal affect during mother-infant interactions
      assessed at 1 month of age. Analyses also indicated a direct association between
      prenatal exposure to cocaine and RSA regulation to negative affect at 7 months of
      age.

PMID- 20047019
TI  - Mindfulness Research Update: 2008.
AB  - OBJECTIVE: To briefly review the effects of mindfulness on the mind, the brain,
      the body, and behavior. METHODS: Selective review of MEDLINE, PsycINFO, and
      Google Scholar databases (2003-2008) using the terms "mindfulness", "meditation",
      "mental health", "physical health", "quality of life", and "stress reduction." A
      total of 52 exemplars of empirical and theoretical work were selected for review.
      RESULTS: Both basic and clinical research indicate that cultivating a more
      mindful way of being is associated with less emotional distress, more positive
      states of mind, and better quality of life. In addition, mindfulness practice can
      influence the brain, the autonomic nervous system, stress hormones, the immune
      system, and health behaviors, including eating, sleeping and substance use, in
      salutary ways. CONCLUSION: The application of cutting-edge technology toward
      understanding mindfulness - an "inner technology" - is elucidating new ways in
      which attention, awareness, acceptance, and compassion may promote optimal health
      - in mind, body, relationships, and spirit.

PMID- 20047020
TI  - Mapping Urban Risk: Flood Hazards, Race, & Environmental Justice In New York"
AB  - This paper demonstrates the importance of disaggregating population data
      aggregated by census tracts or other units, for more realistic population
      distribution/location. A newly-developed mapping method, the Cadastral-based
      Expert Dasymetric System (CEDS), calculates population in hyper-heterogeneous
      urban areas better than traditional mapping techniques. A case study estimating
      population potentially impacted by flood hazard in New York City compares the
      impacted population determined by CEDS with that derived by centroid-containment
      method and filtered areal weighting interpolation. Compared to CEDS, 37 percent
      and 72 percent fewer people are estimated to be at risk from floods city-wide,
      using conventional areal weighting of census data, and centroid-containment
      selection, respectively. Undercounting of impacted population could have serious
      implications for emergency management and disaster planning. Ethnic/racial
      populations are also spatially disaggregated to determine any environmental
      justice impacts with flood risk. Minorities are disproportionately undercounted
      using traditional methods. Underestimating more vulnerable sub-populations
      impairs preparedness and relief efforts.

PMID- 20047021
TI  - Electroosmotic pumps for microflow analysis.
AB  - With rapid development in microflow analysis, electroosmotic pumps are receiving
      increasing attention. Compared to other micropumps, electroosmotic pumps have
      several unique features. For example, they are bi-directional, can generate
      constant and pulse-free flows with flow rates well suited to microanalytical
      systems, and can be readily integrated with lab-on-chip devices. The magnitude
      and the direction of flow of an electroosmotic pump can be changed instantly. In
      addition, electroosmotic pumps have no moving parts. In this article, we discuss
      common features, introduce fabrication technologies and highlight applications of
      electroosmotic pumps.

PMID- 20047023
TI  - Too Tired to Tell the Truth: Self-Control Resource Depletion and Dishonesty.
AB  - The opportunity to profit from dishonesty evokes a motivational conflict between
      the temptation to cheat for selfish gain and the desire to act in a socially
      appropriate manner. Honesty may depend on self-control given that self-control is
      the capacity that enables people to override antisocial selfish responses in
      favor of socially desirable responses. Two experiments tested the hypothesis that
      dishonesty would increase when people's self-control resources were depleted by
      an initial act of self-control. Depleted participants misrepresented their
      performance for monetary gain to a greater extent than did non-depleted
      participants (Experiment 1). Perhaps more troubling, depleted participants were
      more likely than non-depleted participants to expose themselves to the temptation
      to cheat, thereby aggravating the effects of depletion on cheating (Experiment
      2). Results indicate that dishonesty increases when people's capacity to exert
      self-control is impaired, and that people may be particularly vulnerable to this
      effect because they do not predict it.

PMID- 20047022
TI  - Micropatterning of bioactive self-assembling gels.
AB  - Microscale topographical features have been known to affect cell behavior. An
      important target in this area is to integrate top down techniques with bottom up
      self-assembly to create three-dimensional (3D) patterned bioactive mimics of
      extracellular matrices. We report a novel approach toward this goal and
      demonstrate its use to study the behavior of human mesenchymal stem cells
      (hMSCs). By incorporating polymerizable acetylene groups in the hydrophobic
      segment of peptide amphiphiles (PAs), we were able to micro-pattern nanofiber
      gels of these bioactive materials. PAs containing the cell adhesive epitope
      arginine-glycine-aspartic acid-serine (RGDS) were allowed to self-assemble within
      microfabricated molds to create networks of either randomly oriented or aligned
      ~30 nm diameter nanofiber bundles that were shaped into topographical patterns
      containing holes, posts, or channels up to 8 MUm in height and down to 5 MUm in
      lateral dimensions. When topographical patterns contained nanofibers aligned
      through flow prior to gelation, the majority of hMSCs aligned in the direction of
      the nanofibers even in the presence of hole microtextures and more than a third
      of them maintained this alignment when encountering perpendicular channel
      microtextures. Interestingly, in topographical patterns with randomly oriented
      nanofibers, osteoblastic differentiation was enhanced on hole microtextures
      compared to all other surfaces.

PMID- 20047024
TI  - Moderate sedation for echocardiography of preschoolers.
AB  - Preschoolers frequently require sedation for echocardiograms. This study compared
      various sedation drugs at the authors' institution, as well as the charges for
      moderate versus deep sedation. From 2001 to 2007, sedation was administered to
      703 patients ages 2 to 4 years. Four drug regimens were used: chloral hydrate
      (CH), chloral hydrate with diphenhydramine (CH + D), chloral hydrate with
      hydroxyzine hydrochloride (CH + H), and midazolam. The mean onset of sedation was
      37 min, and the mean duration of sedation was 47 min. The CH group fell asleep
      the most quickly (30 min; p < 0.001), and the CH + D patients experienced the
      most prolonged sedations (13%; p < 0.001). Studies were completed by 97% of the
      chloral hydrate group, 98% of the CH + D group, and 94% of the CH + H group
      compared with 66% of the midazolam group (p < 0.001). Complications (7.4%) were
      minor and not significant for any particular medication. The charges for moderate
      sedation averaged $709 compared with $3,628 for deep sedation. The findings
      demonstrated that chloral hydrate was the fastest-acting agent and had a high
      success rate with minimally prolonged sedations. The low complication rate for
      chloral hydrate, and the much lower cost for its use to induce moderate sedation
      have made chloral hydrate our preference for the echocardiographic sedation of
      preschoolers.

PMID- 20047026
TI  - Postnatal growth of rhabdomyoma prior to tumor regression.
AB  - We report a case of a 1-month-old infant with multiple intracardiac rhabdomyomas.
      In contrast to the known natural history of rhabdomyomas to show postnatal
      regression, this patient showed marked tumor progression prior to initiation of
      tumor regression at 10 months of age. In the absence of pronounced cardiovascular
      compromise, this finding should serve to encourage continued conservative
      management of rhabdomyomas despite tumor progression.

PMID- 20047027
TI  - Morphological comparison between adolescent and adult lumbar pedicles using
      computerised tomography scanning.
AB  - BACKGROUND: To study the morphological difference between the lumbar pedicle in
      adolescent and adult groups as only less information is known about their pedicle
      morphology, especially in Malaysian population. METHODS: The pedicle parameters
      of the lumbar spine in adolescent and adult groups including transverse outer
      pedicle diameter, transverse inner pedicle diameters, medial wall cortical
      thickness, lateral wall cortical thickness, pedicle length, transverse pedicle
      angle and sagittal pedicle angle were measured using computerised tomography (CT)
      scanning. The measurements in both groups were compared and analysed using
      statistical method. RESULTS: In adolescent group, the mean transverse outer
      diameter was 8.9 +/- 1.2 mm, transverse inner diameter was 6.3 +/- 1.2 mm, medial
      cortical thickness was 1.6 +/- 1.2 mm, lateral cortical thickness was 1.3 +/- 1.2
      mm, pedicle length was 41.7 +/- 3.8 mm, transverse angle was 20.0 +/- 2.5 degrees
      and sagittal angle was 16.0 +/- 1.7 degrees . In adult group, the mean transverse
      outer diameter was 9.8 +/- 1.3 mm, transverse inner diameter was 7.0 +/- 1.2 mm,
      medial cortical thickness was 1.7 +/- 1.2 mm, lateral cortical thickness was 1.4
      +/- 1.6 mm, pedicle length was 44.8 +/- 5.0 mm, transverse angle was 21.7 +/- 2.3
      degrees and sagittal angle was 17.4 +/- 1.7 degrees . Comparing the mean of the
      two age groups, all the measurements were significantly smaller (p < 0.05) in the
      adolescent patients. CONCLUSIONS: Pedicle morphology in adolescent and adult
      population is different in all parameters, especially in males. Understanding of
      specific pedicle morphology for each group is imperative for safety in spinal
      procedures using pedicle route.

PMID- 20047028
TI  - A genetic locus and gene expression patterns associated with the priming effect
      on lettuce seed germination at elevated temperatures.
AB  - Seeds of most cultivated varieties of lettuce (Lactuca sativa L.) fail to
      germinate at warm temperatures (i.e., above 25-30 degrees C). Seed priming
      (controlled hydration followed by drying) alleviates this thermoinhibition by
      increasing the maximum germination temperature. We conducted a quantitative trait
      locus (QTL) analysis of seed germination responses to priming using a recombinant
      inbred line (RIL) population derived from a cross between L. sativa cv. Salinas
      and L. serriola accession UC96US23. Priming significantly increased the maximum
      germination temperature of the RIL population, and a single major QTL was
      responsible for 47% of the phenotypic variation due to priming. This QTL
      collocated with Htg6.1, a major QTL from UC96US23 associated with high
      temperature germination capacity. Seeds of three near-isogenic lines (NILs)
      carrying an Htg6.1 introgression from UC96US23 in a Salinas genetic background
      exhibited synergistic increases in maximum germination temperature in response to
      priming. LsNCED4, a gene encoding a key enzyme (9-cis-epoxycarotinoid
      dioxygenase) in the abscisic acid biosynthetic pathway, maps precisely with
      Htg6.1. Expression of LsNCED4 after imbibition for 24 h at high temperature was
      greater in non-primed seeds of Salinas, of a second cultivar (Titan) and of NILs
      containing Htg6.1 compared to primed seeds of the same genotypes. In contrast,
      expression of genes encoding regulated enzymes in the gibberellin and ethylene
      biosynthetic pathways (LsGA3ox1 and LsACS1, respectively) was enhanced by priming
      and suppressed by imbibition at elevated temperatures. Developmental and
      temperature regulation of hormonal biosynthetic pathways is associated with seed
      priming effects on germination temperature sensitivity.

PMID- 20047029
TI  - Perceived social support, hope, and quality of life of persons living with
      HIV/AIDS: a case study from Nepal.
AB  - PURPOSE: This study investigates the relationship among perceived satisfaction
      from social support, hope, and QOL of PLWHA. METHOD: A cross-sectional in design
      was applied, among a sample of 160 HIV-infected persons receiving treatment,
      care, and support from eight community-based NGOs. QOL was assessed using the WHO
      (QOL)-26 tool, and social support was assessed by use of a modified Sarason's
      Social Support Questionnaire. A Hope Assessment Scale was also developed.
      RESULTS: The non-family support network was greater than family support network.
      Overall satisfaction from social support and hope was significantly correlated
      with QOL; the greatest effect of social support was on environmental functioning,
      and the lowest was on social relationships, emotional support was less a
      predictor of social relationship than other types of supports. CONCLUSION: The
      effect of perceived satisfaction from social support was through the mediation
      variable hope. As it has widely been recognized that community-based support is
      vital for issues of quality of life, strategies to improve social support and
      hope intervention programs are strongly encouraged. The results of the study have
      implications for providing care, treatment, and psycho-social support to maintain
      or enhance quality of life of PLWHA.

PMID- 20047030
TI  - Translational medicine--a paradigm shift in modern drug discovery and
      development: the role of biomarkers.
AB  - The success rate of novel medical entities that are submitted for registration by
      the regulatory agencies and followed successful marketing has been stagnating for
      the past decade. Failure in efficacy and safety continue to be the prime hurdles
      and causes of failure. Translational medicine is a new function within the
      pharmaceutical industry R&D organization aimed to improve the predictability and
      success of drug discovery and development. Biomarkers are the essence of the
      translational medicine strategy focus on disease biomarker, patient selection,
      pharmacodynamic responses (efficacy and safety) target validation, compound
      target interaction). Successful deployment of biomarkers research, validation and
      implementation is adopted and embraced as key strategy to improved the drug
      discovery and development towards new medical entities.

PMID- 20047031
TI  - Natural products in drug discovery: present status and perspectives.
AB  - Natural products and their derivatives have been and continue to be rich sources
      for drug discovery. However, natural products are not drugs. They are produce in
      nature and through biological assays they are identified as leads, which become
      candidates for drug development. More than 60% of the drugs that are in the
      market derive from natural sources. During the last two decades, research aimed
      at exploiting natural products as a resource has seriously declined. This is in
      part due to the development of new technologies such as combinatorial chemistry,
      metagenomics and high-throughput screening. However, the new drug discovery
      approaches did not fulfilled the initial expectations. This has lead to a renewed
      interest in natural products, determined by the urgent need for new drugs, in
      particular to fight against infections caused by multi-resistant pathogens.

PMID- 20047032
TI  - Protein pharmaceuticals: discovery and preclinical development.
AB  - Proteins are natural molecules that carry out important cellular functions within
      our bodies. Their precise role is crucial to the maintenance of good health.
      Malfunctioning proteins or those not produced optimally result in disease. The
      foundation of biopharmaceutical drug therapy has therefore been to modulate
      cellular function by targeting specific proteins expressed on or outside the
      cell. Because most biopharmaceuticals are natural in origin, they are
      biologically and chemically very different from conventional medicines. In
      addition to differences in mechanism of action, biopharmaceuticals differ in the
      process by which they get manufactured and delivered. Because of their large,
      complex structure, they must often be produced by culturing cells and then
      purified from a host of cellular components. This can be time-consuming and
      costly. Also, most biopharmaceuticals are given by injection under the skin or by
      infusion into the veins. This creates significant limitations to their utility.
      Nonetheless, biopharmaceuticals can be very powerful and selective in disease
      applications such as in rheumatoid arthritis or cancer. This chapter describes
      methods by which proteins drugs are discovered, optimized and developed. It also
      covers novel agents and next generation proteins as well as some of the
      challenges and opportunities in the area.

PMID- 20047033
TI  - The role of nanobiotechnology in drug discovery.
AB  - The potential applications of nanotechnology in life sciences, particularly
      nanobiotechnology, include those for drug discovery. This chapter shows how
      several of the nanotechnologies including nanoparticles and various nanodevices
      such as nanobiosensors and nanobiochips are being used to improve drug discovery.
      Nanoscale assays using nanoliter volumes contribute to cost saving. Some
      nanosubstances such as fullerenes are drug candidates. There are some safety
      concerns about the in vivo use of nanoparticles that are being investigated.
      However, future prospects for applications in healthcare of drugs discovered
      through nanotechnology and their role in the development of personalized medicine
      appear to be excellent.

PMID- 20047034
TI  - Conotoxin venom peptide therapeutics.
AB  - Venom peptides offer enormous opportunity for the discovery of peptide drug
      leads. This review focusses on the potential of cone snails that have developed
      arrays of small peptides as part of highly evolved venoms used for prey capture
      and defence. Many of these peptides selectively modulate ion channels and
      transporters, making them a valuable source of new ligands for studying the role
      these targets play in normal and disease physiology. A number of these
      conopeptides reduce pain in animals models and several are now in preclinical and
      clinical development for the treatment of severe pain often associated with
      diseases such as cancer.

PMID- 20047035
TI  - Shark novel antigen receptors--the next generation of biologic therapeutics?
AB  - Over recent decades we have witnessed a revolution in health care as new classes
      of therapeutics based on natural biological molecules have become available to
      medical practitioners. These promised to target some of the most serious
      conditions that had previously evaded traditional small molecule drugs, such as
      cancers and to alleviate many of the concerns of patients and doctors alike
      regarding adverse side effects and impaired quality of life that are often
      associated with chemo-therapeutics. Many early 'biologics' were based on
      antibodies, Nature's answer to invading pathogens and malignancies, derived from
      rodents and in many ways failed to live up to expectations. Most of these issues
      were subsequently negated by technological advances that saw the introduction of
      human or "humanized' antibodies and have resulted in a number of commercial
      'block-busters'. Today, most of the large pharmaceutical companies have product
      pipelines that include an increasing proportion of biologic as opposed to small
      molecule compounds. The limitations of antibodies or other large protein drugs
      are now being realized however and ever more inventive solutions are being sought
      to develop equally efficacious but smaller, more soluble, more stable and less
      costly alternatives to broaden the range of drug-able targets and therapeutic
      options. The aim of this chapter is to introduce the reader to one such novel
      approach that seeks to exploit a unique antibody-like protein evolved by
      ancestral sharks over 450 M years ago and that may lead to a host of new
      therapeutic opportunities and help us to tackle some of the pressing clinical
      demands of the 21 st century.

PMID- 20047036
TI  - Immune interventions of human diseases through toll-like receptors.
AB  - Toll-like receptors (TLRs) are the immune sensors for infections, triggering
      robust innate immune activation followed by protective adaptive immunity against
      various infectious diseases. Recent evidence, however, has suggested that TLRs
      are involved in the pathogenesis of many diseases, including not only infectious
      diseases but also autoimmune diseases, allergy and atherosclerosis. Therefore,
      prophylactic or therapeutic application of TLR-based immune interventions should
      be potent, but their safety must be demonstrated using experimental animal models
      as well as human resources, including analysis of single nucleotide
      polymorphisms. Here, we focus on recent advances in understanding of the
      protective and pathogenic roles of TLRs in human diseases.

PMID- 20047037
TI  - Genome-based vaccine development: a short cut for the future.
AB  - Bacterial infectious diseases remain a major cause of deaths and disabilities in
      the world. Although conventional vaccinology approaches were successful in
      conferring protection against several diseases, they failed in providing
      efficient vaccines against many others. Together to the sequencing of the first
      genome, a new chapter in the vaccinology history started to be written. Reverse
      vaccinology changed the way to think about vaccine development, using the
      information provided by the microorganisms' genome against themselves. Since
      then, reverse vaccinology has evolved and helped researchers to overcome the
      limits of the conventional vaccinology approaches and led to the discovery and
      development of novel vaccines concerning emerging diseases, like Neisseria
      meningitidis B and Streptococcus agalactiae. A lot of work must be done, but
      deciphering the information provided by genome sequences and using it to better
      understand the host-pathogen interactions has proved to be the key for
      protection.

PMID- 20047038
TI  - The antigenome: from protein subunit vaccines to antibody treatments of bacterial
      infections?
AB  - New strategies are needed to master infectious diseases. The so-called "passive
      vaccination", i.e., prevention and treatment with specific antibodies, has a
      proven record and potential in the management of infections and entered the
      medical arena more than 100 years ago. Progress in the identification of specific
      antigens has become the hallmark in the development of novel subunit vaccines
      that often contain only a single immunogen, frequently proteins, derived from the
      microbe in order to induce protective immunity. On the other hand, the monoclonal
      antibody technology has enabled biotechnology to produce antibody species in
      unlimited quantities and at reasonable costs that are more or less identical to
      their human counterparts and bind with high affinity to only one specific site of
      a given antigen. Although, this technology has provided a robust platform for
      launching novel and successful treatments against a variety of devastating
      diseases, it is up till now only exceptionally employed in therapy of infectious
      diseases. Monoclonal antibodies engaged in the treatment of specific cancers seem
      to work by a dual mode; they mark the cancerous cells for decontamination by the
      immune system, but also block a function that intervenes with cell growth. The
      availability of the entire genome sequence of pathogens has strongly facilitated
      the identification of highly specific protein antigens that are suitable targets
      for neutralizing antibodies, but also often seem to play an important role in the
      microbe's life cycle. Thus, the growing repertoire of well-characterized protein
      antigens will open the perspective to develop monoclonal antibodies against
      bacterial infections, at least as last resort treatment, when vaccination and
      antibiotics are no options for prevention or therapy. In the following chapter we
      describe and compare various technologies regarding the identification of
      suitable target antigens and the foundation of cognate monoclonal antibodies and
      discuss their possible applications in the treatment of bacterial infections
      together with an overview of current efforts.

PMID- 20047039
TI  - HSV as a vector in vaccine development and gene therapy.
AB  - The very deep knowledge acquired on the genetics and molecular biology of herpes
      simplex virus (HSV), major human pathogen whose lifestyle is based on a long-term
      dual interaction with the infected host characterized by the existence of lytic
      and latent infections, has allowed the development of potential vectors for
      several applications in human healthcare. These include delivery and expression
      of human genes to cells of the nervous system, selective destruction of cancer
      cells, prophylaxis against infection with HSV or other infectious diseases and
      targeted infection of specific tissues or organs. Three different classes of
      vectors can be derived from HSV-1: replication-competent attenuated vectors,
      replication-incompetent recombinant vectors and defective helper-dependent
      vectors known as amplicons. This chapter highlights the current knowledge
      concerning design, construction and recent applications, as well as the potential
      and current limitations of the three different classes of HSV-1-based vectors.

PMID- 20047040
TI  - Virus-like particles as a vaccine delivery system: myths and facts.
AB  - Vaccines against viral disease have traditionally relied on attenuated virus
      strains or inactivation of infectious virus. Subunit vaccines based on viral
      proteins expressed in heterologous systems have been effective for some
      pathogens, but have often suffered from poor immunogenicity due to incorrect
      protein folding or modification. In this chapter we focus on a specific class of
      viral subunit vaccine that mimics the overall structure of virus particles and
      thus preserves the native antigenic conformation of the immunogenic proteins.
      These virus-like particles (VLPs) have been produced for a wide range of
      taxonomically and structurally distinct viruses, and have unique advantages in
      terms of safety and immunogenicity over previous approaches. With new VLP
      vaccines for papillomavirus beginning to reach the market place we argue that
      this technology has now 'come-of-age' and must be considered a viable vaccine
      strategy.

PMID- 20047041
TI  - Applications of bacterial ghosts in biomedicine.
AB  - Bacterial Ghosts (BG) are empty cell envelopes of Gram-negative bacteria which
      have been produced by E-mediated lysis. BG are devoid of cytoplasmic content and
      in combination with the expression of the nuclease SNUC, BG are also devoid of
      chromosomal and plasmid DNA. Proof of concept and proof of principle studies
      showed that BG candidate vaccines are highly immunogenic and in many instances
      induce protective immunity against lethal challenge in animal models. Due to
      their nature of being bacterial envelope complexes, BG are endowed with intrinsic
      natural adjuvant activity. BG are able to stimulate the innate and adaptive
      immune system without any addition of exogenous adjuvants. Although the use of
      plasmid encoded genetic information is essential for the final make up of BG, BG
      are not to be considered as genetically manipulated organisms (GMO), as they are
      nonliving and devoid of genetic information. The latter aspect is of great
      importance for safety, as no pathogenic islands or antibiotic resistance
      cassettes can be transferred to other bacteria by horizontal gene transfer. This
      is an important difference to other chemical-, heat- and pressure- or radiation
      inactivated vaccine candidates, which also very often need artificial adjuvants
      to be added to improve their immunogenicity. The final BG vaccine preparations
      are freeze dried and are stable for many years at ambient temperature. BG can
      also be used as carrier and delivery vehicles for drugs or active substances in
      tumor therapy and due to specific targeting of tumor cells allow a higher
      specificity of treatment and a reduction of the total amount of drug per
      application. As carrier of enzymatic activity BG can be used for a new concept of
      probiotics which can synthesise active compounds from substrates of the
      environment where they are applied with a certain preference for the gut system.
      Thus, BG represent a promising technology platform for novel vaccines including
      combination or DNA vaccines, as drug carriers for therapeutic approaches in tumor
      treatment and as novel probiotics.

PMID- 20047042
TI  - Immune modulators with defined molecular targets: cornerstone to optimize
      rational vaccine design.
AB  - Vaccination remains the most valuable tool for preventing infectious diseases.
      However, the performance of many existing vaccines should be improved and there
      are diseases for which vaccines are still not available. The use of well-defined
      antigens for the generation of subunit vaccines has led to products with an
      improved safety profile. However, purified antigens are usually poorly
      immunogenic, making essential the use of adjuvants. Despite the fact that
      adjuvants have been used to increase the immunogenicity of vaccines for more than
      70 years, only a handful has been licensed for human use (e.g., aluminium salts,
      the micro-fluidized squalene-in-water emulsion MF59 and monophosphoryl lipid A).
      Thus, the development of new adjuvants which are able to promote broad and
      sustained immune responses at systemic and mucosal levels still remains as a
      major challenge in vaccinology. Recent advances in our understanding of the
      immune system have facilitated the identification of new biological targets for
      screening programs aimed at the discovery of novel immune stimulators. This
      resulted in the identification of new candidate adjuvants, which made possible
      the modulation of the immune responses elicited according to specific needs. A
      number of promising adjuvants which are currently under preclinical or clinical
      development will be described in this chapter.

PMID- 20047043
TI  - Innovative approaches to develop prophylactic and therapeutic vaccines against
      HIV/AIDS.
AB  - The acquired immunodeficiency syndrome (AIDS) emerged in the human population in
      the summer of 1981. According to the latest United Nations estimates, worldwide
      over 33 million people are infected with human immunodeficiency virus (HIV) and
      the prevalence rates continue to rise globally. To control the alarming spread of
      HIV, an urgent need exists for developing a safe and effective vaccine that
      prevents individuals from becoming infected or progressing to disease. To be
      effective, an HIV/AIDS vaccine should induce broad and long-lasting humoral and
      cellular immune responses, at both mucosal and systemic level. However, the
      nature of protective immune responses remains largely elusive and this represents
      one of the major roadblocks preventing the development of an effective vaccine.
      Here we summarize our present understanding of the factors responsible for
      resistance to infection or control of progression to disease in human and monkey
      that may be relevant to vaccine development and briefly review recent approaches
      which are currently being tested in clinical trials. Finally, the rationale and
      the current status of novel strategies based on nonstructural HIV-1 proteins,
      such as Tat, Nef and Rev, used alone or in combination with modified structural
      HIV-1 Env proteins are discussed.

PMID- 20047044
TI  - New strategies to overcome the drawbacks of currently available flu vaccines.
AB  - Vaccination represents the most efficient tool to control morbidity and mortality
      resulting from influenza infections in humans. The currently licensed influenza
      vaccines provide good protection levels in healthy adults, whereas lower
      protection is generally achieved in ageing individuals who are at a higher risk
      of developing severe clinical manifestations. Future improvements in influenza
      vaccines should address the needs of high risk groups including the elderly,
      small children and chronic patients. Recently, due to the increased incidence of
      avian influenza pandemic outbreaks, the prevention of a potential human influenza
      pandemic turned into another crucial issue in the influenza vaccination field.
      The development and validation of manufacturing processes for efficient and safe
      pandemic vaccines became one of the top priorities of health, regulatory and
      funding agencies all over the world. In the pandemic context, the development of
      novel vaccines administered via the mucosal route may play a significant role by
      reducing virus shedding from infected individuals. This chapter provides insights
      in the limitations of existing manufacturing processes, new approaches to
      overcome limitation in vaccine production, mechanisms of action of current
      vaccines and discuss potential strategies to improve the immunogenicity and
      efficacy of influenza vaccines.

PMID- 20047045
TI  - Carnosine supplementation protects rat brain tissue against ethanol-induced
      oxidative stress.
AB  - Ethanol causes oxidative stress and tissue damage. The aim of this study was to
      investigate the effect of antioxidant carnosine on the oxidative stress induced
      by ethanol in the rat brain tissue. Forty male rats were divided equally into
      four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus
      carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected
      intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day
      ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH
      + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals
      were sacrificed using ketamine and brain tissues were removed. Malondialdehyde
      (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide
      dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain
      tissue specimens were significantly increased in the CAR and EtOH groups when
      compared to the control animals. MDA and PCO levels in the EtOH group were
      significantly increased as compared to the other groups (P < 0.05). CAR treatment
      also decreased MDA levels in the CAR group as compared to the control group.
      Increased SOD activities were obtained in the EtOH + CAR group as compared to the
      control (P < 0.05). CAR levels in the rat brain were significantly increased in
      the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These
      findings indicated that carnosine may appear as a protective agent against
      ethanol-induced brain damage.

PMID- 20047046
TI  - Exogenously expressed human Ku70 stabilizes Ku80 in Xenopus oocytes and induces
      heterologous DNA-PK catalytic activity.
AB  - The Ku protein is a heterodimer composed of 70 kD (Ku70) and 80 kD (Ku80)
      subunits. Ku is the regulatory component of the DNA-dependent protein kinase (DNA
      PK) that has a catalytic subunit of approximately 460 kD (DNA-PK(cs)). In this
      study, the two polypeptides (Ku80/Ku70) of the human Ku were expressed in Xenopus
      oocytes in order to investigate their over-expression, sub-cellular localization,
      and functional interaction with the Xenopus DNA-PK(cs). In vitro-transcribed
      mRNAs for Ku70 and Ku80 were obtained from the respective plasmid constructs. The
      exogenously expressed proteins from the injected mRNAs were immunoprecipitated
      using a specific anti-T7 Tag antibody. The T7 Tag epitope is present in the
      vector at the amino-terminus and is in-frame with the Ku cDNA sequences. While
      injected Ku70 mRNA translated to a full-length Ku70 polypeptide that translocated
      to the nucleus, injected Ku80 mRNA resulted in the expression of a truncated
      product that was retained in the cytoplasm. Although Ku80 mRNA was stable for a
      period of 18 h in the oocytes post-microinjection, the protein was only
      stabilized when co-expressed with Ku70, suggesting that Ku80 is susceptible to
      proteolytic degradation when not dimerized with Ku70. Furthermore, the
      immunocomplex was capable of phosphorylating the DNA-PK-specific substrate
      thereby indicating that the holoenzyme could functionally reconstitute in vivo in
      the oocytes by heterologous subunits thus demonstrating evolutionary conservation
      of the enzyme subunit structure and function among diverse species.

PMID- 20047047
TI  - Lipid peroxidation in the fungus Curvularia lunata exposed to nickel.
AB  - The effect of Ni(2+) on fungal growth, cellular fatty acid profile and lipid
      peroxidation was studied (with an emphasis on the kinetics of these processes) in
      the strain of filamentous fungus Curvularia lunata. In the cultures supplemented
      with 0.2 and 0.6 mM Ni(2+) the lag phase was extended and the specific growth
      rate decreased, however, the maximum yield of biomass at the stationary phase
      reached, respectively, 97 and 27% of the control. The treatment with Ni(2+)
      changed the proportion of 18 C atom fatty acids, with the most significant
      decrease in the content of linoleic acid (18:2) followed by a rise in the degree
      of fatty acid saturation. In the mycelia exposed to Ni(2+) the levels of TBARS
      (lipid peroxidation products) increased and ranged between 156 and 823% over the
      control. The presented data reveal that the oxidative stress resulting, among
      others, in membrane lipid peroxidation is involved in the mechanisms of the
      nickel toxicity towards C. lunata and suggest that this fungus exhibits an
      ability to cope, to some extent, with the increased level of lipid peroxides.

PMID- 20047048
TI  - Camptosemin, a tetrameric lectin of Camptosema ellipticum: structural and
      functional analysis.
AB  - Lectins have been classified into a structurally diverse group of proteins that
      bind carbohydrates and glycoconjugates with high specificity. They are extremely
      useful molecules in the characterization of saccharides, as drug delivery
      mediators, and even as cellular surface makers. In this study, we present
      camptosemin, a new lectin from Camptosema ellipticum. It was characterized as an
      N-acetyl-D-galactosamine-binding homo-tetrameric lectin, with a molecular weight
      around 26 kDa/monomers. The monomers were stable over a wide range of pH values
      and exhibited pH-dependent oligomerization. Camptosemin promoted adhesion of
      breast cancer cells and hemagglutination, and both activities were inhibited by
      its binding of sugar. The stability and unfolding/folding behavior of this lectin
      was characterized using fluorescence and far-UV circular dichroism
      spectroscopies. The results indicate that chemical unfolding of camptosemin
      proceeds as a two-state monomer-tetramer process. In addition, small-angle X-ray
      scattering shows that camptosemin behaves as a soluble and stable homo-tetramer
      molecule in solution.

PMID- 20047049
TI  - Comparative study of the pneumatization of the mastoid air cells and paranasal
      sinuses using three-dimensional reconstruction of computed tomography scans.
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      the pneumatization of mastoid air cells and PNS using three-dimensional (3D)
      reconstruction of computed tomography (CT) scans of the PNS. METHODS: A
      retrospective review of PNS CT scans from 60 cases was performed. Patients with
      evidence of sinusitis or mastoiditis, or a history of head trauma, were excluded
      from the study. Volumes were measured using 3D reconstruction based on axial
      images of 1 mm thickness. Volumes of the mastoid air cells (right and left),
      frontal sinus, sphenoid sinus, and maxillary sinuses (right and left) were
      obtained and compared using statistical analysis. RESULTS: The volume of mastoid
      air cells and sinuses did change with age, but the volumes of male subjects were
      larger than those of females. There was a positive correlation between the
      pneumatization of mastoid air cells and that of the sphenoid sinus; however, no
      relationship was observed between the volume of mastoid air cells and that of the
      maxillary sinuses. CONCLUSIONS: This study examined whether a similarity in
      pneumatization exists between the mastoid air cells and PNS of individuals; these
      results may be useful in understanding the normal and pathological conditions of
      both structures.

PMID- 20047050
TI  - Localization of pterion in neonatal cadavers: a morphometric study.
AB  - PURPOSE: Pterion is defined as a junction of temporal, frontal, parietal, and
      sphenoid bones. In newborns, pterion may be defined as a region that shows
      variability in the exact location because of the lack of complete bony structure.
      The aim of this study is to define the topographic anatomy of this important
      surgical point, pterion, and the variability of its localization on craniums of
      newborn cadavers. METHODS: Our study was performed using 35 term neonatal cadaver
      specimens. We measured the distances between the pterion and other critical
      points and used a scale diagram for the definition of pterional area. RESULTS:
      Our scale diagram showed that pterion is mostly localized in regions c, d, e, and
      f on the length and regions 2, 3, 4, and 5 on the width. Localization was not
      observed in regions a, b, g, and h, and in areas of squares 1 and 6. The most
      observed localization of pterion was the e4 (24.28%) area. CONCLUSION: This study
      provides a detailed knowledge on localization of this important point, pterion,
      which will be useful for the clinicians at operation planning and treatment
      stages, serving for the success in surgery in the presence of this variable
      topographic cranial anatomy.

PMID- 20047051
TI  - Impact of routine angiographic follow-up after percutaneous coronary drug-eluting
      stenting for unprotected left main disease: the Turin Registry.
AB  - BACKGROUND: Most cardiologists performing percutaneous coronary intervention
      (PCI) with drug-eluting stents (DES) for unprotected left main disease (ULM)
      mandate mid-term angiographic follow-up, yet there are few data supporting this
      approach. We aimed to retrospectively compare the outcome of patients with ULM
      treated with DES according to their follow-up management strategy. METHODS:
      Patients with ULM stenosis undergoing PCI with DES and surviving up to 6 months
      were retrospectively identified from our ongoing database. We distinguished those
      undergoing clinical follow-up only, those with clinically driven angiographic
      follow-up, and those with routine angiographic follow-up. The primary end-point
      was the long-term rate of major adverse cardiac events (MACE, i.e., death,
      myocardial infarction, bypass surgery, or repeat ULM PCI). RESULTS: A total of
      198 patients were included: 55 (28%) in the clinical follow-up group, 64 (32%) in
      the clinically driven angiographic follow-up group, and 79 (40%) in the routine
      angiographic follow-up group. After 37.0 +/- 15.7 months, mortality was similar
      in the 3 groups (respectively 7.3, 4.7, and 5.9%, p = 0.27). However, MACE were
      significantly more common in the clinically driven angiographic follow-up group
      (42.2 vs. 7.3 and 26.1%, p = 0.02), mainly due to the expected increase in repeat
      revascularization in those undergoing angiographic follow-up (23.4 vs. 1.8 and
      13.14%). Notably, there were no differences in the rate of stent thrombosis
      across the three groups, with rates of 3.1 vs. 1.8 and 2.5% (p = 0.35).
      CONCLUSIONS: An expectant management can be safely adopted in most patients with
      ULM treated percutaneously, as long as a low threshold for control coronary
      angiography is maintained.

PMID- 20047053
TI  - Comparison of early onset breast cancer patients to older premenopausal breast
      cancer patients.
AB  - BACKGROUND: The objective of this study was to show differences between breast
      cancer patients < or =35 and >35 years with regard to tumor characteristics and
      to present the patient-relevant outcomes overall survival (OAS) and recurrence
      free survival (RFS). METHODS: We analyzed data from 119 women aged 35 years or
      younger with breast cancer and compared multiple parameters against breast cancer
      patients between 36 and 55 (n = 1,097), all pre-menopausal. Data were adjusted
      for tumor characteristics and therapy. RESULTS: There was no statistically
      significant difference in tumor size, axillary lymph node involvement, and
      histological subtypes. On the contrary, grading lymphovascular invasion and
      receptor negativity showed statistically significant differences. Unadjusted
      hazard ratio are 2.11 (1.32-3.39) (OAS) and 1.92 (1.35-2.73) (RFS). Multi
      adjusted hazard ratio are 2.97 (1.70-5.18) (OAS) and 2.11 (1.42-3.13) (RFS).
      CONCLUSIONS: In conclusion, young breast cancer patients still have a poor
      prognosis. Even after adjustment of the data, OAS and RFS showed a worse
      prognosis. Normal prognostic factors like tumor size, axillary lymph node
      involvement, and grading can therefore be not the explanation for the more
      aggressive disease progress within early onset breast cancer patients.

PMID- 20047052
TI  - Intravascular ultrasound study and evidence of pathological coronary flow reserve
      in patients with isolated coronary artery aneurysms.
AB  - OBJECTIVES: Isolated coronary artery aneurysms (CA) are defined as non
      obstructive lesions with luminal dilation > or =2-fold of normal coronary
      diameters. METHODS: A coronary sinus study with incremental atrial pacing was
      performed in 19 patients with bilateral fusiform CA to investigate myocardial
      ischemia. Intravascular ultrasound was performed to characterize the lesions
      morphology. The average peak velocity in the aneurysmatic segment of the left
      anterior descending artery was simultaneously measured by a Doppler flow wire.
      Coronary flow volumes, vascular resistances and flow reserve after administration
      of papaverin were calculated. Ten patients without heart disease served as a
      control group (CG). RESULTS: Intravascular ultrasound revealed large true CA with
      a cross-sectional area of 34.2 +/- 4.1 mm(2) and only slight atherosclerosis.
      Exercise-induced myocardial ischemia was found in CA presenting with a cardiac
      lactate production and an only 1.6-fold increase in coronary blood flow. A
      significant smaller coronary flow reserve of 1.51 was revealed in CA when
      compared with CG (2.86, P < 0.02) corresponding to a coronary vascular resistance
      of 0.59 versus 0.35 (P < 0.03) mmHg (ml/min) after papaverin. CONCLUSIONS:
      Coronary artery aneurysms were unequivocally identified as an entity of ischemic
      non-obstructive coronary artery disease with a markedly reduced flow reserve.

PMID- 20047054
TI  - Association of serum relaxin with striae gravidarum in pregnant women.
AB  - AIMS: The cause of striae gravidarum is still unclear. The study objective was to
      test the hypothesis that relaxin is involved in the process of striae gravidarum
      appearance during pregnancy. METHODS: A prospective observational study in 32
      pregnant women. Participants were observed at 12th, 24th and 36th gestational
      week. During each session, striae scoring was assessed and blood for relaxin
      estimation was withdrawn. The striae assessment was done according to Davey
      score. Serum relaxin was estimated using Relaxin ELISA kit (Immunodiagnostic AG,
      Bensheim, Germany). RESULTS: Serum relaxin levels decreased as the pregnancy
      advanced (585.9 +/- 295.1, 424.2 +/- 253.8, 402.1 +/- 221.2 pg/ml, respectively)
      but this decrease did not attain statistical significance. Pregnant women with
      striae gravidarum had lower serum relaxin levels compared to those without striae
      gravidarum at 36th gestational weeks, 330.8 +/- 175.2 vs 493.8 +/- 245.8 pg/ml (P
      = 0.037), respectively. The severity of striae gravidarum during pregnancy did
      not correlate with serum relaxin levels. CONCLUSION: Lower serum relaxin levels
      could contribute to the occurrence of striae gravidarum during pregnancy through
      decreased elasticity of the connective tissue.

PMID- 20047055
TI  - Pharmacogenetics of antidepressive treatment.
AB  - The search of the genetic predictors of response to antidepressants is a rapidly
      expanding field. A large number of clinical studies are reporting partly
      inconsistent results. Emerging new results focus on new candidate single
      nucleotide polymorphisms--particularly in the 5HT2a-receptor gene and the gene
      coding for the co-chaperone FKBP5. The impact of the 5HTTLPR polymorphism on
      therapeutic outcome and side effects under treatment with SSRIs has to be viewed
      in a more complex manner than previously proposed. All replicable genetic
      associations display only a very modest effect. Despite of enormous research
      efforts, currently pharmacogenetics of therapeutic effects and of side effects of
      antidepressants are unable to guide decisions on the selection of the most
      beneficial drug for an individual patient.

PMID- 20047056
TI  - Unilateral reduced sense of smell is an early indicator for global olfactory
      loss.
AB  - It is estimated that 15% of normosmic subjects demonstrate lateralized smell
      loss. The majority of individuals will not notice this difference between
      nostrils as long as olfactory function of the better nostril remains in the
      normal range. We were interested in the question whether subjects demonstrating
      clinically significant side differences of olfactory function are at risk to
      develop bilateral olfactory loss. Normosmic individuals with such side
      differences ("difference group", n = 35) were re-tested on average 4.6 years
      after baseline investigations. Additionally, 58 subjects who did not demonstrate
      side differences ("control group") were also re-investigated. All participants
      received detailed olfactory testing using the "Sniffin' Sticks" involving tests
      for odor threshold, odor discrimination, and odor identification. Olfactory
      testing at follow-up indicated lower olfactory function (p = 0.005) in the
      "difference group" than in the "control group". The degree of side difference at
      baseline correlated negatively with the results from olfactory testing at follow
      up (r = -0.29; p = 0.01). These results suggest that individuals with side
      differences of olfactory function are at risk to develop bilateral olfactory loss
      within 4.5 years. Thus, the degree of lateralized smell function is an indicator
      for future smell loss.

PMID- 20047057
TI  - Acute brain MRI-DWI patterns and stroke recurrence after mild-moderate stroke.
AB  - Brain ischemic lesions identified by diffusion-weighted imaging (DWI) have been
      shown to predict high risk of early future ischemic events in patients with
      transient ischemic attacks and minor stroke. The aim of this study is to analyze
      different brain MRI-DWI patterns in patients with mild-moderate stroke to define
      acute patterns related with a higher risk of stroke recurrence in long-term
      follow-up (from 6 to 36 months). Retrospective review of case series from a
      prospective stroke record including 253 patients with mild-moderate stroke (NIHSS
      from 1 to 7) and acute MRI-DWI lesions. MRI-DWI lesions were analyzed to
      determine clinically relevant lesions, based on the number, location, age and
      affected arterial territories. We defined three patterns: (1) multiple versus
      single lesions; (2) single deep versus single cortical lesions; and (3) single
      lesions versus multiple lesions affecting different arterial territories and/or
      of different age. The impact of these patterns on recurrence was analyzed by Cox
      regression analysis. 38 patients (15.0%) suffered a recurrence. Univariate
      analysis showed the risk of recurrence for each pattern. Pattern 1: patients with
      multiple lesions had greater risk of recurrence than those with single lesions
      (28.2 vs. 9.9%; OR: 3.75 (95% CI: 1.76-7.27), p < 0.0001). Pattern 2: patients
      with single cortical lesions had higher risk than those with deep lesions (14.3
      vs. 6.7% OR: 2.33 (95% CI: 0.86-6.33), p < 0.089). Pattern 3: patients with
      multiple DWI in different territories or different age had the highest recurrence
      rate (30.6%), OR: 4.01 (95% CI: 1.70-9.47), p < 0.001, compared to patients with
      single lesions. Cox regression analysis adjusted by possible confounders, showed
      that for pattern 1 the OR for recurrence was 2.49 (95% CI: 1.27-4.89), p = 0.008;
      for pattern 2, OR:1.99 (95% CI: 0.74-5.37), p = 0.17; for pattern 3, OR: 2.85
      (95% CI: 1.31-6.15), p = 0.008. Brain MRI-DWI patterns assessed in the acute
      phase of mild-moderate stroke are useful to identify those patients at high risk
      of recurrence.

PMID- 20047058
TI  - Multiple cerebral infarctions in a patient with Churg-Strauss syndrome.
AB  - Neurological manifestation of Churg-Strauss syndrome (CSS) is common and usually
      consists of peripheral neuropathy due to small-vessel vasculitis, while cerebral
      manifestation is less frequent. We report the case of a 77-year-old woman with
      multiple cerebral infarctions and hypereosinophilia. The presence of
      hypereosinophilia, asthma, sinusitis and vasculitis led to the diagnosis of CSS.
      As cerebral infarctions occurred monophasically and an elevation of heart enzymes
      was present, we assumed cardiac involvement and multiple cerebral infarctions due
      to cardiac embolism. Treatment with high-dose IV methylprednisone and
      cyclophosphamide pulses led to significant improvement. This case illustrates
      multiple cerebral infarctions in CSS. CSS should always be considered in patients
      with hypereosinophilia and stroke.

PMID- 20047059
TI  - Insensitivity of visual assessment of hippocampal atrophy in familial Alzheimer's
      disease.
AB  - Medial temporal atrophy is a well-established marker for Alzheimer's disease
      (AD). However, due to normal variation in the size of medial temporal structures
      and variability in how radiologists interpret images, the use of clinical reads
      in establishing the presence of pathological atrophy is imprecise. A limitation
      of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic
      uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to
      develop AD and most subjects do not undergo autopsy verification of the
      diagnosis. In persons with or at-risk for AD due to fully-penetrant autosomal
      dominant mutations in the PSEN1 and APP genes, the diagnosis or future
      development of AD can be predicted with essentially 100% accuracy. We used this
      predictability to assess the ability of radiologists to detect hippocampal
      atrophy (HA) in persons destined to develop AD. Coronal T1-weighted MRI scans of
      39 persons demented from (n = 4) or at-risk for inheriting (n = 35) PSEN1 or APP
      mutations were independently assessed by two radiologists and the presence or
      absence of HA determined. Of the 39 subjects, 26 were FAD mutation carriers.
      Fifteen of 28 asymptomatic at-risk persons were FAD mutation carriers and four of
      these were rated as having atrophy for a sensitivity of 27% and a specificity of
      85%. Among seven mildly affected yet non-demented subjects, atrophy was detected
      in three and in the four demented subjects HA was identified in two. Our results
      suggest that radiologists' ability to detect HA in persons in whom the diagnosis
      of incipient AD is certain is sub-optimal and quantitative MRI techniques or
      other biological markers of the disease are needed.

PMID- 20047060
TI  - Occupational silica exposure as a risk factor for scleroderma: a meta-analysis.
AB  - OBJECTIVES: Among potential environmental risk factors for systemic sclerosis
      (SSc), occupational exposures have received some attention. In this meta
      analysis, we examined the association between SSc and occupational exposure to
      silica. METHODS: We searched Medline, Toxline, BIOSIS, and Embase (1949 and
      November 2009) for original articles published in any language. Sixteen studies
      are included in the analysis, of which, 3 are cohort studies, 9 case-control and
      4 are of other designs. The combined estimator of relative risk (CERR) and 95%
      confidence interval (CI) were calculated using fixed or random effect models.
      RESULTS: Significant heterogeneity was detected (I (2) = 97.2%; P < 0.01), and
      the CERR was 3.20 (95% CI, 1.89-5.43). The CERR for studies in females was 1.03
      (95% CI, 0.74-1.44) and was 3.02 (95% CI, 1.24-7.35) for males. The CERR for case
      control studies was 2.24 (95% CI, 1.65-3.31) and was 15.49 (95% CI, 4.54-52.87)
      for cohort studies. CONCLUSIONS: The findings suggest that silica exposure may be
      a significant risk factor for developing SSc and specifically in males. Further
      observational studies examining the role of occupational silica exposure in the
      context of other risk factors are needed.

PMID- 20047062
TI  - The association of disproportionate skeletal growth and abnormal radius dimension
      ratio with curve severity in adolescent idiopathic scoliosis.
AB  - Abnormal anthropometric measurements during the peripubertal growth spurt have
      been documented in adolescent idiopathic scoliosis (AIS). Magnetic resonance (MR)
      imaging studies of the spine have suggested a disproportionate endochondral and
      membranous ossification in AIS. The present study aimed at investigating whether
      disproportional ossification and skeletal growth occurred in the peripheral bone
      of AIS patients using the radius as the target bone. Skeletally mature AIS girls
      with different severity (n = 290) and age-matched control healthy girls (n = 80)
      were recruited. The anthropometric parameters were recorded. The midshaft of non
      dominant radius was scanned with peripheral quantitative computed tomography
      (pQCT) and the radius diameter was calculated from the cross-sectional area.
      Radius dimension ratio was derived from the ratio of radius diameter to radius
      length. The anthropometric parameters were compared between AIS and control with
      adjustment for age. The radius dimension ratio was further correlated with curve
      severity in AIS girls using Pearson's correlation test. The analysis showed that
      the arm span and radius length were slightly longer in AIS girls. The BMI of AIS
      girls was significantly lower than the controls. The radius dimension ratio in
      severe AIS girls was significantly lower than the controls and the ratio of AIS
      girls correlated with the curve severity (r = -0.120; p = 0.039). The abnormal
      radius dimension ratio supported the presence of systemic growth abnormalities in
      AIS. Disproportional endochondral-membranous ossification could explain for the
      observation. The observation of the association of radius dimension ratio with
      curve severity provides an important potentially clinically measurable parameter
      for further longitudinal studies on the prognostication of curve progression in
      AIS.

PMID- 20047061
TI  - Hierarchical fine mapping of the cystic fibrosis modifier locus on 19q13
      identifies an association with two elements near the genes CEACAM3 and CEACAM6.
AB  - On 19q13, TGFB1 and the cystic fibrosis modifier 1 locus (CFM1) have been
      identified as modifiers of the course of the monogenic disease cystic fibrosis
      (CF). Recently, we have described a transmission disequilibrium at the
      microsatellite D19S197, localized between TGFB1 and CFM1. To map the
      corresponding molecular variants, we have selected informative SNP markers within
      a 600-kb area and compared two-marker-haplotype-distributions between
      phenotypically contrasting sib pair groups, intending to type only
      phylogenetically old markers by aiming for close-to-maximal polymorphism
      information content of the SNPs. Starting with a seed set of five SNPs that cover
      intermarker distances of up to 50 kb, we have iteratively added more SNPs to the
      map, until we could identify two genomic fragments of 3,289 and 2,052 bp for
      which pairs with contrasting phenotypes showed different haplotype distributions
      on the final 17-SNP-map (P(raw) = 0.0002, P(corr17SNPs) = 0.0106 and P(raw) =
      0.0008, P(corr17SNPs) = 0.0469, respectively). Resequencing of these fragments of
      four unrelated individuals for each element showed that the mildly and severely
      affected pairs differ in seven SNPs and concordant pairs differ from discordant
      pairs in five SNPs. Annotation of these variants indicate that CEACAM6 and a
      regulatory element near the 3' end of CEACAM3 are associated with CF disease
      severity and intrapair discordance, respectively. While our approach was only
      guided by the markers' position, the involvement of genes from the CEACAM family
      in host defense and innate immunity designates these proteins as likely modifiers
      of the multi-organ disease cystic fibrosis which is known for its cytokine
      imbalance and pro-inflammatory phenotype.

PMID- 20047063
TI  - Total serum cholesterol levels and suicide attempts in child and adolescent
      psychiatric inpatients.
AB  - Associations between cholesterol and suicidal behavior in adolescent patients
      have not been explored in depth. In this study, 66 patients consecutively
      admitted to a psychiatric inpatient unit following attempted suicide were
      compared with a control group of 54 patients with no history of suicide attempts.
      The age range of the sample was from 8 to 18 years old. Cholesterol levels were
      significantly lower in attempted suicide patients than in controls (p < 0.02),
      supporting the hypothesis that lower cholesterol levels might be associated with
      suicidal behavior in patients with similar acute phase of their disorder.

PMID- 20047064
TI  - High-yield production of citric acid by Yarrowia lipolytica on glycerol in
      repeated-batch bioreactors.
AB  - An acetate negative mutant of Yarrowia lipolytica Wratislavia AWG7 was found to
      be suitable for the production of high amounts of citric acid in long-term
      repeated-batch cultures. When 40% of fresh replaced medium was fed, this strain
      produced 154 g l(-1), on average, which corresponded to a 0.78 g g(-1) yield and
      a productivity of 1.05 g l(-1) h(-1). The activity of the culture remained stable
      for more than 1,650 h, i.e., 16 cycles of the repeated-batch bioreactors.

PMID- 20047066
TI  - Platelet-rich plasma and 1,25(OH)2 vitamin D3 synergistically stimulate
      osteogenic differentiation of adult human mesenchymal stem cells.
AB  - Mesenchymal stem cell proliferation and differentiation are regulated by growth
      factors and systemic hormones in a concerted manner. We have examined the effects
      of platelet-rich plasma (PRP) and its interaction with 1,25(OH)(2) vitamin D(3)
      [1,25(OH)(2)D(3)] on the differentiation and proliferation of human mesenchymal
      stem cells (hMSCs). PRP stimulated cell proliferation in a manner inversely
      proportional to the dose. Exposure to PRP inhibited hMSC osteogenic
      differentiation. Co-treatment with PRP and 1,25(OH)(2)D(3), however,
      synergistically stimulated osteogenic differentiation. Serial co-treatment with
      PRP and 1,25(OH)(2)D(3) showed that this synergistic effect was due to the
      modulation of a 1,25(OH)(2)D(3)-induced differentiation by PRP rather than vice
      versa.

PMID- 20047067
TI  - Mycogenic metal nanoparticles: progress and applications.
AB  - Nanotechnology is relevant to diverse fields of science and technology. Due to
      the many advantages over non-biological systems, several research groups have
      exploited the use of biological systems for the synthesis of nanoparticles. Among
      the different microbes used for the synthesis of nanoparticles, fungi are
      efficient candidates for fabrication of metal nanoparticles both intra- and
      extracellulary. The nanoparticles synthesized using fungi present good
      polydispersity, dimensions and stability. The potential applications of
      nanotechnology and nanoparticles in different fields have revolutionized the
      health care, textile and agricultural industries and they are reviewed here.

PMID- 20047068
TI  - Fusion expression of cecropin B-like antibacterial peptide in Escherichia coli
      and preparation of its antiserum.
AB  - Antibacterial peptides have a broad range of antibacterial properties that makes
      them highly toxic for expression in Escherichia coli. For prepare an antiserum to
      detect these peptides, we developed a cecropin B mutant with a green fluorescent
      protein fusion partner resulting in high expression of a 37 kDa fusion peptide in
      E. coli with a yield of 7.9 mg/l culture medium after purification on Ni-IDA
      resin. Guinea pigs when immunized with the fusion peptide produced a specific
      antiserum which titers in excess of 1:25,600.

PMID- 20047069
TI  - In vivo effects of NbSiR silencing on chloroplast development in Nicotiana
      benthamiana.
AB  - Sulfite reductase (SiR) performs dual functions, acting as a sulfur assimilation
      enzyme and as a chloroplast (cp-) nucleoid binding protein. In this study, we
      examined the in vivo effects of SiR deficiency on chloroplast development in
      Nicotiana benthamiana. Virus-induced gene silencing of NbSiR resulted in leaf
      yellowing and growth retardation phenotypes, which were not rescued by cysteine
      supplementation. NbSiR:GFP fusion protein was targeted to chloroplasts and
      colocalized with cp-nucleoids. Recombinant full-length NbSiR protein and the C
      terminal half of NbSiR possessed cp-DNA compaction activities in vitro, and
      expression of full-length NbSiR in E. coli caused condensation of genomic DNA.
      NbSiR silencing differentially affected expression of plastid-encoded genes,
      inhibiting expression of several genes more severely than others. In the later
      stages, depletion of NbSiR resulted in chloroplast ablation. In NbSiR-silenced
      plants, enlarged cp-nucleoids containing an increased amount of cp-DNA were
      observed in the middle of the abnormal chloroplasts, and the cp-DNAs were
      predominantly of subgenomic sizes based on pulse field gel electrophoresis. The
      abnormal chloroplasts developed prolamellar body-like cubic lipid structures in
      the light without accumulating NADPH:protochlorophyllide oxidoreductase proteins.
      Our results suggest that NbSiR plays a role in cp-nucleoid metabolism, plastid
      gene expression, and thylakoid membrane development.

PMID- 20047070
TI  - Ghrelin and obestatin expression in oral squamous cell carcinoma: an
      immunohistochemical and biochemical study.
AB  - The underlying molecular mechanism of carcinogenesis in oral squamous cell
      carcinoma (OSCC) is poorly understood and appears to be controlled on many
      genetic, environmental, and hormonal factors. Obestatin and ghrelin, two recently
      discovered hormones, are co-expressed in endocrine cells. The purpose of this
      investigation was to examine the immunohistochemical features of OSCCs in
      relation to the tissue concentration of ghrelin and obestatin. The association
      between OSCC and Epstein Barr Virus (EBV) status was also explored. The
      expression of ghrelin and obestatin was examined by immunohistochemistry and
      immunoassay in oral biopsy specimens: 10 benign squamous epithelial cell samples,
      10 microinvasive squamous cell carcinomas, and seven well-differentiated and
      seven poorly differentiated OSCCs. The presence of EBV was evaluated in these
      samples using immunohistochemistry. The concentrations of ghrelin and obestatin
      in tissue homogenates were measured by RIA and ELISA, respectively. Squamous cell
      carcinomas and benign tissue samples were positive for anti-EBV antibody, and
      obestatin and ghrelin were shown to be co-expressed in all stratified squamous
      epithelium samples. Expression of ghrelin and obestatin was decreased or absent
      in OSCCs in relation to the invasiveness of the carcinoma; ghrelin and obestatin
      levels in cancerous tissue homogenates were lower than in benign tissue
      homogenates. These results indicate that the concentrations and distribution of
      immunoreactive obestatin and ghrelin might be helpful in distinguishing OSCC from
      benign tumors. Maintaining normal levels of these hormones might be required for
      regulation of normal cell division. However, detailed studies will be required
      for better understanding of the complex mechanism of carcinogenesis relating to
      OSCCs.

PMID- 20047071
TI  - Alterations in erythrocyte membrane fluidity and Na+/K+ -ATPase activity in
      chronic alcoholics.
AB  - Ethanol disorders biological membranes causing perturbations in the bilayer and
      also by altering the physicochemical properties of membrane lipids. But, chronic
      alcohol consumption also increases nitric oxide (NO) production. There was no
      systemic study was done related to alcohol-induced production of NO and
      consequent formation of peroxynitrite mediated changes in biophysical and
      biochemical properties, structure, composition, integrity and function of
      erythrocyte membranes in chronic alcoholics. Hence, keeping all these conditions
      in mind the present study was undertaken to investigate the role of over produced
      nitric oxide on red cell membrane physicochemical properties in chronic
      alcoholics. Human male volunteers aged 44 +/- 6 years with similar dietary habits
      were divided into two groups, namely nonalcoholic controls and chronic alcoholics
      (~125 g of alcohol at least five times per week for the past 10-12 years).
      Elevated nitrite and nitrate levels in plasma and lysate, changes in erythrocyte
      membrane individual phospholipid composition, increased lipid peroxidation,
      protein carbonyls, cholesterol and phospholipids ratio (C/P ratio) and
      anisotropic value (gamma) with decreased sulfhydryl groups and Na(+)/K(+)-ATPase
      activity in alcoholics was evident from this study. RBC lysate NO was positively
      correlated with C/P ratio (r = 0.547) and anisotropic (gamma) value (r = 0.428),
      Na(+)/K(+)-ATPase activity was negatively correlated with RBC lysate NO (r = 
      0.372) and anisotropic (gamma) value (r = -0.624) in alcoholics. Alcohol-induced
      overproduction of nitric oxide reacts with superoxide radicals to produce
      peroxynitrite, which appears to be responsible for changes in erythrocyte
      membrane lipids and the activity of Na(+)/K(+)-ATPase.

PMID- 20047072
TI  - High-altitude adaptation of yak based on genetic variants and activity of lactate
      dehydrogenase-1.
AB  - This study investigates the molecular mechanism by which yaks (Bos grunniens)
      adapt to hypoxia based on lactate dehydrogenase (LDH). Three LDH1 variants of the
      yak were revealed in tissue extracts by electrophoresis, including LDH1-F, LDH1
      M, and LDH1-S. Kinetic analysis using purified LDH1 variants showed that the yak
      LDH1-M variant exhibited a similar K (m) (NADH) and the same mobility on a gel as
      bovine LDH1, and the LDH1-F variant showed significant differences in K (m)
      values for NADH or pyruvate from the other two variants of yak LDH1 and bovine
      LDH1. Among the three muscles assayed, yak longissimus dorsi showed the highest
      LDH activity and the lowest malate dehydrogenase (MDH) activity; heart muscle was
      exactly the opposite. Our results suggest that the three LDH1 variants might play
      an important role in the adaptation to hypoxia.

PMID- 20047073
TI  - Demographic history and population structure of blackfin flounder (Glyptocephalus
      stelleri) in Japan revealed by mitochondrial control region sequences.
AB  - The demographic history and population genetic structure of the blackfin flounder
      (Glyptocephalus stelleri) along coastal regions of Japan were investigated.
      Genetic variation in DNA sequences was examined from the first hypervariable
      region of the mitochondrial DNA control region. A high level of haplotypic
      diversity (h = 0.99 +/- 0.004) was detected, indicating a high level of
      intrapopulation genetic diversity. The starburst structure of the minimum
      spanning tree suggested a very recent origin for most haplotypes. The demographic
      history of G. stelleri was examined using neutrality tests and mismatch
      distribution analysis, which also indicated a Pleistocene population expansion at
      about 124,100-413,400 years ago. Hierarchical molecular variance analysis and
      conventional population Fst comparisons revealed no significant genetic
      differentiation throughout the range examined.

PMID- 20047074
TI  - Apoptosis and its functional significance in molluscs.
AB  - Programmed cell death leading to apoptosis is essential for normal development
      and homeostasis in plants and throughout the animal kingdom. Although there are
      differences in apoptotic mechanisms between lower animals and vertebrates,
      crucial biochemical components of the programmed cell death pathways remained
      remarkably conserved throughout evolution. Despite decades of studies on the
      neurobiology and development of mollusks, comparatively little is known about the
      mechanisms of apoptosis in this phylum. In this review, an attempt is made to
      summarize data obtained on mollusks so far, and to discuss the molecular
      mechanisms, the functional and ecological significance of apoptosis and the
      advantages of snail preparations as tools for programmed cell death research. A
      definitive comparison of the data obtained on mollusks with those obtained on the
      more widely studied vertebrates, will contribute to the better understanding of
      the apoptotic process in general and of its evolutionary development.

PMID- 20047075
TI  - Potassium humate inhibits carrageenan-induced paw oedema and a graft-versus-host
      reaction in rats.
AB  - It has been shown in a previous study that brown coal-derived potassium humate is
      safe and effective in suppressing contact hypersensitivity in rats. In this study
      the efficacy of potassium humate on other types of inflammation was determined.
      Preparative TLC followed by mass spectroscopy was used in an attempt to
      fingerprint the product. The effects of potassium humate, at an oral dose of 60
      mg/kg bodyweight, on a delayed type hypersensitivity reaction, a carrageenan
      induced inflammation model and an allogeneic graft-versus-host reaction (GVHR) in
      rats were investigated. Paw oedema was used as a measure of inflammation. It was
      found that potassium humate had no effect on the delayed type hypersensitivity
      reaction but significantly inhibited the increase in paw volume of the
      carrageenan-induced oedema in rats which compared favourably with indomethacin
      treatment. Furthermore, potassium humate inhibited the GVHR induced in normal and
      cyclophosphamide-treated immune-incompetent rats. The identification of a
      naturally occurring compound that is safe and effective in reducing different
      types of inflammation merits further evaluation in clinical trials.

PMID- 20047076
TI  - Fragile X mental retardation protein in learning-related synaptic plasticity.
AB  - Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation
      protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP
      is thought to contribute to synaptic plasticity by regulating plasticity-related
      protein synthesis and other signaling pathways. Previous studies have mostly
      focused on the roles of FMRP within the hippocampus--a key structure for spatial
      memory. However, recent studies indicate that FMRP may have a more general
      contribution to brain functions, including synaptic plasticity and modulation
      within the prefrontal cortex. In this brief review, we will focus on recent
      studies reported in the prefrontal cortex, including the anterior cingulate
      cortex (ACC). We hypothesize that alterations in ACC-related plasticity and
      synaptic modulation may contribute to various forms of cognitive deficits
      associated with FXS.

PMID- 20047077
TI  - Serum response factor is essential for the proper development of skin epithelium.
AB  - Mammalian epidermis is a stratified epithelium that serves as a barrier
      protecting the organism from mechanical stress and dehydration. Previous studies
      have demonstrated the importance of the actin cytoskeleton in the establishment
      of a functional skin epithelium. Despite what is known about the actin
      cytoskeleton in epithelial sheet formation, the molecules important for
      controlling the actin cytoskeleton during epidermal development have not been
      determined. Serum response factor (SRF) is a transcription factor that is
      considered to be an important regulator of the actin cytoskeleton. To examine the
      role of SRF in the developing mouse epidermis, we have employed gene targeting to
      ablate Srf in keratinocytes. Conditional inactivation of Srf during the embryonic
      timepoint leads to a defect in the organization of the epidermis.
      Immunohistochemical analyses demonstrated a marked loss of the filamentous actin
      cytoskeleton and E-cadherin localization in epidermis, as well as an aberration
      in the localization of tight junction proteins. Moreover, impairment of the
      "inside-out" epidermal barrier was shown. Srf conditional knockout keratinocytes
      are unable to establish proper intercellular connections or form an epithelial
      sheet as shown by histological examination and induced keratinocyte
      differentiation experiments. Our results demonstrate that Srf is essential for
      the actin-mediated sealing of epithelial cell-cell contacts and the development
      of functional stratified skin epithelium in vivo.

PMID- 20047078
TI  - Downregulation of cough by exercise and voluntary hyperpnea.
AB  - No information exists on the effects of hyperpnea on the sensory and cognitive
      aspects of coughing evoked by inhalation of tussigenic agents. The threshold for
      the cough reflex induced by inhalation of increasing concentrations of
      ultrasonically nebulized distilled water (fog), and the index of cough reflex
      sensitivity, was assessed in 12 healthy humans in control conditions, during
      exercise, and during voluntary isocapnic hyperventilation (VIH) to the same level
      as the exercise. The intensity of the urge-to-cough (UTC), a cognitive component
      of coughing, was also recorded throughout the trials. The log-log relationship
      between inhaled fog concentrations and the correspondingly evoked UTC values, an
      index of the perceptual magnitude of the UTC sensitivity, was also calculated.
      Cough appearance was always assessed audiovisually. At an exercise level of 80%
      of anaerobic threshold, the mean cough threshold was increased from a control
      value of 1.03 +/- 0.65 to 2.25 +/- 1.14 ml/min (p < 0.01), i.e., cough
      sensitivity was downregulated. With VIH, the mean (+/-SD) threshold increased
      from 1.03 +/- 0.65 to 2.42 +/- 1.16 ml/min (p < 0.01), a similar downregulation.
      With exercise and VIH compared with control, mean UTC values at cough threshold
      were not significantly changed: control, 3.83 +/- 1.11 cm; exercise, 3.12 +/-
      0.82 cm; VIH, 4.08 +/- 1.67 cm. Since the slopes of the log fog concentration/log
      UTC value were approximately halved during exercise and VIH compared with
      control, the UTC sensitivity to fog was depressed (p < 0.01). The results
      indicate that the adjustments brought into action by exercise-induced or
      voluntary hyperventilation exert inhibitory influences on the sensory and
      cognitive components of fog-induced cough.

PMID- 20047079
TI  - FMD, reproducibility, and acute exercise in the obese: are the results
      confounded?

PMID- 20047080
TI  - High-dose antithrombin III prevents heat stroke by attenuating systemic
      inflammation in rats.
AB  - OBJECTIVE: Systemic inflammatory mediators, including the high mobility group box
      1 (HMGB1) protein, play important roles in the development of various
      inflammatory conditions. Although anticoagulants, such as antithrombin III (AT
      III), inhibit inflammation resulting from various causes, their anti-inflammatory
      mechanism of action is not well understood. Nevertheless, as heat stroke is a
      severe inflammatory response disease, we hypothesized that AT III would inhibit
      inflammation and prevent heat stress-induced acute heat stroke. METHODS: Male
      Wistar rats received a bolus injection of saline or 250 U of AT III per kg of
      body weight into the tail vein, followed by heat stress (exposure to 42 degrees C
      for 30 min). Levels of cytokines (interleukin-1 beta, interleukin-6, and TNF
      alpha), NOx, and HMGB1 were measured in serum and tissue at regular intervals for
      6 h after the heat stress induction. RESULTS: Levels of cytokines, NOx, and HMGB1
      in serum decreased over time in AT III-treated rats. AT III pretreatment also
      reduced NOx levels during heat stress-induced inflammation. As a result, AT III
      pretreatment improved survival in a rat model of heat stress-induced acute
      inflammation. CONCLUSIONS: Our data suggest that AT III pretreatment inhibited
      the secretion of cytokines, NOx, and HMGB1, and prevented heat stress-induced
      acute inflammation.

PMID- 20047082
TI  - Exfoliating goblet cell hyperplasia mimicking pterygium: a clinicopathological
      case report.
AB  - We present an interventional case report of exfoliating goblet cell hyperplasia
      mimicking pterygium. A 44-year-old male with bilateral lesions of the nasal
      bulbar conjunctiva extending over the cornea, consistent with pterygia, underwent
      surgical excision of the lesion in his left eye. Histopathologic examination
      revealed an exophytic lesion made up of proliferated goblet cells with benign
      cytologic features. Some of the goblet cells were atrophic and seemed to be
      desquamating from the lesion surface. Cytologic examination of a tear specimen
      collected from the right eye revealed the presence of exfoliated goblet cells
      admixed with mucin material. The lesion had not recurred three months after
      surgery. Exfoliating goblet cell hyperplasia, a condition not previously reported
      on the ocular surface, may mimic pterygium. Histopathologic examination is
      required to establish the diagnosis.

PMID- 20047081
TI  - Associations between plasma insulin-like growth factor-I and the markers of
      inflammation interleukin 6, C-reactive protein and YKL-40 in an elderly
      background population.
AB  - BACKGROUND AND OBJECTIVE: The objective of the present study was to test the
      hypothesis that circulating levels of insulin-like growth factor-I (IGF-I) are
      inversely associated with inflammatory processes in an elderly background
      population. PATIENTS AND DESIGN: We conducted a population-based study comprising
      629 individuals, aged 50-89 years. Associations between plasma IGF-I versus
      interleukin 6 (IL-6) and the acute phase proteins high sensitive C-reactive
      protein (hsCRP) and YKL-40 were evaluated by linear regression analyses.
      Subsequently, the population was dichotomised at a CRP level of 3.0 mg/L and the
      associations were re-evaluated in the two subgroups. RESULTS: Adjusted for
      confounding variables, plasma IGF-I was inversely related to IL-6, hsCRP and YKL
      40 (all P < 0.001). The strongest association was found for YKL-40 with a 34%
      reduction in YKL-40 per twofold increase in IGF-I. A significant inverse
      association between IGF-I and all markers of inflammation persisted in
      individuals with hsCRP below 3.0 mg/L whereas only YKL-40 was significantly
      associated with IGF-I in individuals with hsCRP above 3.0 mg/L. CONCLUSIONS: The
      data support the hypothesis of an inverse association between GH/IGF-I signalling
      and inflammation, and suggest that the relationship between the IGF-I and
      inflammation might be more predominant in healthy individuals with a low
      inflammatory activity.

PMID- 20047083
TI  - Lottery ticket preferences as indicated by the variation in the number of
      winners.
AB  - Many gamblers believe that it is possible to find a strategy to beat the lottery
      including selecting numbers that are due to come up or looking for a bias in past
      numbers. In this paper, we examine sales figures and variations in the number of
      winners for the various prize levels of a popular Canadian lottery to detect
      lottery ticket preferences. It was determined that the lottery outcomes conformed
      well to a random outcome. No evidence of either a bias myth or due to come up
      myth was found. However ticket popularity indicated a marked preference for the
      number 7 and low numbers, and the avoidance of high numbers and adjacent numbers.
      In addition we found a linear and a quadratic relationship between past frequency
      of the numbers and ticket popularity indicating a belief in both the due to come
      up and the bias myths. The findings suggest strong non-random preferences in the
      selection of lottery numbers.

PMID- 20047084
TI  - The effect of school dropout on verbal ability in adulthood: a propensity score
      matching approach.
AB  - Compared to high school graduates, adolescents who drop out of school are more
      likely to have a range of negative outcomes, including lower verbal capacities;
      however, the true nature of this association is not well-understood. Dropping out
      of school could have an important effect on reducing verbal skills, or the link
      between dropping out of school and diminished verbal skills could be a spurious
      association that is the result of unmeasured confounding variables. The current
      study tested these two competing perspectives by using propensity-score-matching
      (PSM) to unpack the association between school dropout and verbal skills among
      7,317 respondents from the National Longitudinal Study of Adolescent Health (51%
      female, 49% male; 62% Caucasian, 38% minority). The results of the PSM models
      indicated a small yet meaningful statistically significant effect of dropout on
      verbal skills in adulthood even after taking into account a range of confounders.
      We conclude by discussing the implications of our results.

PMID- 20047085
TI  - An examination of social disorganization and pluralistic neighborhood theories
      with rural mothers and their adolescents.
AB  - Neighborhoods matter for youth; yet, most literature focuses on neighborhood
      deficits rather than strengths. To understand how best to capture neighborhoods,
      this study used census- and perception-based measures of neighborhood
      characteristics as suggested by social disorganization and pluralistic
      neighborhood theories, respectively, to determine the association between
      structural characteristics and perceptions of positive and negative neighborhood
      characteristics. The ethnically diverse (59% White and 34% African American)
      sample (N = 1,414) consisted of early adolescents (53% female) and their mothers.
      We found that participants perceived distinct positive and negative neighborhood
      characteristics. For adolescents and mothers, neighborhood structural
      characteristics were positively associated with risk perceptions (e.g., physical
      and social disorder) but differently associated with positive neighborhood
      characteristics. In addition, participants perceived their neighborhoods
      differently (e.g., adolescents perceived less informal social control but more
      cohesion than their mothers). We discuss the importance of the neighborhood
      context, particularly positive neighborhood characteristics, for rural families.

PMID- 20047086
TI  - Health and role functioning: the use of focus groups in the development of an
      item bank.
AB  - BACKGROUND: Role functioning is an important part of health-related quality of
      life. However, assessment of role functioning is complicated by the wide
      definition of roles and by fluctuations in role participation across the life
      span. The aim of this study is to explore variations in role functioning across
      the lifespan using qualitative approaches, to inform the development of a role
      functioning item bank and to pilot test sample items from the bank. METHODS:
      Eight focus groups were conducted with a convenience sample of 38 English
      speaking adults recruited in Rhode Island. Participants were stratified by gender
      and four age groups. Focus groups were taped, transcribed, and analyzed for
      thematic content. RESULTS: Participants of all ages identified family roles as
      the most important. There was age variation in the importance of social life
      roles, with younger and older adults rating them as more important. Occupational
      roles were identified as important by younger and middle-aged participants. The
      potential of health problems to affect role participation was recognized.
      Participants found the sample items easy to understand, response options
      identical in meaning and preferred five response choices. CONCLUSIONS:
      Participants identified key aspects of role functioning and provided insights on
      their perception of the impact of health on their role participation. These
      results will inform item bank generation.

PMID- 20047087
TI  - Somatically ill persons' self-nominated quality of life domains: review of the
      literature and guidelines for future studies.
AB  - OBJECTIVE: To review which domains somatically ill persons nominate as
      constituting their QoL. Specific objective is to examine whether the method of
      enquiry affect these domains. METHODS: We conducted two literature searches in
      the databases PubMed/Medline, CINAHL and Psychinfo for qualitative studies
      examining patients' self-defined QoL domains using (1) SEIQoL and (2) study
      specific questions. For each database, two researchers independently assessed the
      eligibility of the retrieved abstracts and three researchers subsequently
      classified all QoL domains. RESULTS: Thirty-six eligible papers were identified:
      27 studies using the SEIQoL, and nine presenting data derived from study-specific
      questions. The influence of the method of enquiry on patients' self-nominated QoL
      domains appears limited: most domains were presented in both types of studies,
      albeit with different frequencies. CONCLUSIONS: This review provides a
      comprehensive overview of somatically ill persons' self-nominated QoL domains.
      However, limitations inherent to reviewing qualitative studies (e.g., the varying
      level of abstraction of patients' self-defined QoL domains), limitations of the
      included studies and limitations inherent to the review process, hinder cross
      study comparisons. Therefore, we provide guidelines to address shortcomings of
      qualitative reports amenable to improvement and to stimulate further improvement
      of conducting and reporting qualitative research aimed at exploring respondents'
      self-nominated QoL domains.

PMID- 20047088
TI  - Convulsant action of diphenyl diselenide in rat pups: measurement and correlation
      with plasma, liver and brain levels of compound.
AB  - Diphenyl diselenide [(PhSe)2], an organoselenium compound, presents toxicological
      effects in rat pups, manifested by the appearance of seizure episodes. The aim of
      this study was to carry out the determination and quantification of (PhSe)2 in
      plasma, liver and brain of rat pups after oral administration (p.o) of this
      compound (500 mg/kg). The second objective of this study was to correlate the
      latency to the appearance for the first seizure episode with (PhSe)2 plasma,
      liver and brain levels. Analysis of (PhSe)2 in plasma, liver and brain samples
      was performed by gas chromatography/flame ionized detector system (GC/FID). The
      average levels of (PhSe)2 in plasma, liver and brain of rat pups were 3.67, 5.07
      and 1.15 microg/ml, respectively, at 20.58 min post dosing, the latency media for
      the first seizure episode. (PhSe)2 levels in plasma did not correlate with the
      latency for the first seizure episode induced by this compound. A significant
      negative correlation between the latency for the first seizure episode and the
      levels of (PhSe)2 liver and brain of rat pups was found. It demonstrates that rat
      pups which had highest levels of (PhSe)2 in liver and brain showed the shortest
      latency for the first seizure episode.

PMID- 20047089
TI  - Multi-muscle synergies in a dual postural task: evidence for the principle of
      superposition.
AB  - We used the framework of the uncontrolled manifold hypothesis to quantify multi
      muscle synergies stabilizing the moment of force about the frontal axis (M(Y))
      and the shear force in the anterior-posterior direction (F(X)) during voluntary
      body sway performed by standing subjects. We tested a hypothesis whether the
      controller could stabilize both M(Y) and F(X) at the same time when the task and
      the visual feedback was provided only on one of the variables (M(Y)). Healthy
      young subjects performed voluntary body sway in the anterior-posterior direction
      while different loads were attached at the ankle level producing horizontal
      forces acting forward or backwards. Principal component analysis was used to
      identify three M-modes within the space of integrated indices of muscle
      activation. Variance in the M-mode space across sway cycles was partitioned into
      two components, one that did not affect a selected performance variable (M(Y) or
      F(X)) and the other that did. Under all loading conditions and for each
      performance variable, a higher value for the former variance component was found.
      We interpret these results as reflections of two multi-M-mode synergies
      stabilizing both F(X) and M(Y). The indices of synergies were modulated within
      the sway cycle; both performance variables were better stabilized when the body
      moved forward than when it moved backward. The results show that the controller
      can use a set of three elemental variables (M-modes) to stabilize two performance
      variables at the same time. No negative interference was seen between the synergy
      indices computed for the two performance variables supporting the principle of
      superposition with respect to multi-muscle postural control.

PMID- 20047090
TI  - Grabbing subitizing with both hands: bimanual number processing.
AB  - Visual judgment of small numerosities (<4) is generally assumed to be done
      through subitizing, which is a faster process than counting. Subitizing has also
      been shown to occur in haptic judgment of the number of spheres in the hand.
      Furthermore, interactions have been shown to exist between visually perceived
      numbers and hand motor action. In this study, we compare enumeration of a set of
      spheres presented to one hand (unimanual) and enumeration of the same total
      number of spheres presented divided over the two hands (bimanual). Our results
      show that, like in vision, a combination of subitizing and counting is used to
      process numbers in active touch. This shows that numbers are processed in a
      modality-independent way. This suggests that there are not only interactions
      between perception of numbers and hand motor action, but rather that number
      representation is modality-independent.

PMID- 20047091
TI  - Site of stimulation effects on the prevalence of the tactile motion aftereffect.
AB  - The motion aftereffect (MAE) refers to the apparent motion of a stationary
      stimulus following adaptation to a continuously moving stimulus. There is a
      growing consensus that the fast adapting (FA) rather than the slowly adapting
      (SA) afferent units mediate the tactile version of the MAE. The present study
      investigated which FA units underlie the tactile MAE by measuring its prevalence,
      duration, and vividness on different skin areas that vary in their composition of
      FA units. Specifically, the right cheek, volar surface of the forearm, and volar
      surface of the hand were adapted using a ridged cylindrical drum, which rotated
      at 60 rpm for 120 s. Although there was no difference in duration or vividness
      between the skin surfaces tested, the tactile MAE was reported twice as often on
      the hand compared to the cheek and forearm, which did not differ significantly
      from one another. This suggests that the FA I units in the glabrous skin and the
      hair follicle and/or the FA I and field units in the hairy skin contribute to the
      tactile MAE.

PMID- 20047092
TI  - The effect of menthol application to the skin on sweating rate response during
      exercise in swimmers and controls.
AB  - We tested the hypothesis that menthol application would reduce the magnitude and
      initiation of sweating via excitation of cold-sensitive afferent pathways and
      concurrently via a cross-inhibition of heat loss pathways in acclimatized
      (swimmers, SW) and non acclimatized (control, CON) subjects in cool water. It was
      expected this effect to be exaggerated in SW subjects. Eight SW and eight CON
      subjects cycled at 60% of their VO(2)max, as long as to reach 38 degrees C in
      rectal temperature (Tre), without or with (4.6 g per 100 ml of water) all-body
      application of menthol sediment. Heart rate (HR), Tre, sweating rate (SwR), the
      proximal-distal skin temperature gradient (TSk(f-f)), and oxygen consumption
      (VO(2)) were measured continuously. VO(2) and HR were similar between groups and
      conditions. Menthol increased TSk(f-f), Tre threshold for SwR [+0.32 (0.01)
      degrees C] and Tre gain, while menthol reduced exercise time by 8.1 (4.1) min. SW
      group showed higher changes in Tre threshold for SwR [+0.50 (0.01) degrees C for
      SW vs. +0.13 (0.03) degrees C for CON], higher Tre gain, lower time for Tre
      increase and shorter exercise time [-10.7 (7) min for SW vs. -4.9 (4) min for
      CON] in menthol condition. Upon exercise initiation, previously applied menthol
      on the skin seems to induce vasoconstriction, results in a delayed sweating,
      which in turn affects the rectal temperature. Acclimatized subjects showed higher
      delay in SwR and earlier rise in Tre, which most probably is due to the inter
      group differences in cold receptors activity.

PMID- 20047093
TI  - Effects of ageing and fitness on skin-microvessel vasodilator function in humans.
AB  - The impact of cardiopulmonary fitness (VO(2max)) on the age-related decline in
      skin-microvessel vasodilator function has not been fully established and the
      inter-relationships among different measures of microvascular vasodilator
      function are unknown. We used laser Doppler flowmetry to assess relative changes
      in forearm skin blood flow to various stimuli in three groups of adults: young (n
      = 15; 27 +/- 2 years), older sedentary (n = 14; 65 +/- 6 years) and older fit (n
      = 15; 61 +/- 5 years). Local-heating induced and post-occlusive hyperaemia
      responses were higher in the young and older fit groups compared to the older
      sedentary group (P < 0.05) and were moderately correlated with VO(2max) in the
      pooled cohort of older adults (r = 0.49-0.58; P < 0.05). Peak hyperaemia
      responses to acetylcholine and sodium nitroprusside were higher in young compared
      to older sedentary adults (P < 0.05) and were not associated with VO(2max) in
      older adults (P > 0.05). Associations among different measures of microvascular
      vasodilator function were generally moderate at best. In summary, the local
      heating and reactive hyperaemia data indicate that the age-related decline in
      skin-microvessel vasodilator function can be ameliorated through regular aerobic
      exercise training. As this is not supported by the iontophoresis data, we
      recommend that, when assessing microvascular function, the use of a single
      physiological or pharmacological stimulation coupled to laser Doppler flowmetry
      should be avoided. Finally, the moderate correlations between outcomes probably
      reflect the distinct mediators that are responsible for the vasodilator response
      to each test.

PMID- 20047094
TI  - The function of ADAMTS13 in thrombogenesis in vivo: insights from mutant mice.
AB  - Recently, two independent groups have established ADAMTS13-deficient mice using
      gene-targeting techniques. In humans, genetic or acquired deficiency in ADAMTS13
      leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP).
      Surprisingly, ADAMTS13-deficient mice are viable with no apparent signs of TTP.
      However, these mouse models indicate that ADAMTS13 down-regulates platelet
      adhesion and aggregation in vivo, and ADAMTS13 deficiency can provide enhanced
      thrombus formation at the site of vascular lesions. In addition, ADAMTS13 by
      cleaving hyperactive ultra-large von Willebrand factor multimers not only down
      regulates thrombosis but also inflammation. ADAMTS13-congenic mice that carry a
      truncated form of ADAMTS13 lacking the C-terminal domains have also been
      developed. Phenotypes of the congenic mice indicate the physiological
      significance of the C-terminal domains of ADAMTS13 in down-regulating thrombus
      growth. The studies mentioned here in different mouse models uncover the in vivo
      function of ADAMTS13 and strengthened the understanding of the mechanism of
      systemic disease TTP.

PMID- 20047095
TI  - Comparative analysis of remission induction therapy for high-risk MDS and AML
      progressed from MDS in the MDS200 study of Japan Adult Leukemia Study Group.
AB  - A total of 120 patients with high-risk myelodysplastic syndrome (MDS) and AML
      progressed from MDS (MDS-AML) were registered in a randomized controlled study of
      the Japan Adult Leukemia Study Group (JALSG). Untreated adult patients with high
      risk MDS and MDS-AML were randomly assigned to receive either idarubicin and
      cytosine arabinoside (IDR/Ara-C) (Group A) or low-dose cytosine arabinoside and
      aclarubicin (CA) (Group B). The remission rates were 64.7% for Group A (33 of 51
      evaluable cases) and 43.9% for Group B (29 out of 66 evaluable cases). The 2-year
      overall survival rates and disease-free survival rates were 28.1 and 26.0% for
      Group A, and 32.1 and 24.8% for Group B, respectively. The duration of CR was
      320.6 days for Group A and 378.7 days for Group B. There were 15 patients who
      lived longer than 1,000 days after diagnosis: 6 and 9 patients in Groups A and B,
      respectively. However, among patients enrolled in this trial, intensive
      chemotherapy did not produce better survival than low-dose chemotherapy. In
      conclusion, it is necessary to introduce the first line therapy excluding the
      chemotherapy that can prolong survival in patients with high-risk MDS and MDS
      AML.

PMID- 20047096
TI  - Blimp-1 is a tumor suppressor gene in lymphoid malignancies.
AB  - B lymphocyte-induced maturation protein (Blimp-1) is a transcriptional factor,
      which controls the terminal differentiation of mature B cells to plasma cells.
      Blimp-1 is also called positive regulatory domain I-binding factor-1 (PRDI-BF1)
      or PR (PRDI-BF1-RIZ) domain zinc finger protein 1 (PRDM1). Furthermore, Blimp-1
      is located in chromosome 6q21-22.1, a region frequently deleted in several tumors
      including lymphoid malignancies and has been supposed to be a candidate of tumor
      suppressor gene. Recently, mutational inactivation of Blimp-1 has been identified
      in a subset of diffuse large B-cell lymphomas of the activated B-cell type. In
      addition, an important role for Blimp-1 in maintaining the homeostasis of
      effector T cells is emerging and high expression of Blimp-1beta, a splicing
      variant of Blimp-1, have been presumed to be associated with poor prognosis in T
      cell lymphoma although this aspect of the gene needs further investigation. For
      this reason, we focused on the tumor suppressor function of Blimp-1 on not only B
      but also T cell malignancies in this review.

PMID- 20047097
TI  - A man with concomitant polycythaemia vera and chronic myeloid leukemia: the
      dynamics of the two disorders.
AB  - The co-occurrence of JAK2 V617F mutation with BCR-ABL reciprocal translocation is
      uncommon. We report a 60-year-old man who initially presented with phenotype of
      polycythemia vera (PV), which evolved into chronic myeloid leukemia and back to
      PV once treatment with imatinib was commenced. JAK2 V617F mutation and BCR-ABL
      fusion transcripts were detected in the initial sample. However, JAK2 V617F
      alleles diminished when BCR-ABL mRNA burden increased and reappeared once the
      patient was commenced on imatinib. The dynamic interaction between JAK2 V617F and
      BCR-ABL implies that two independent clones exist with the JAK2 V617F clone only
      achieving clonal dominance when BCR-ABL positive clones are suppressed by
      imatinib.

PMID- 20047098
TI  - Cerebral venous sinus thrombosis after allogeneic stem cell transplantation.

PMID- 20047099
TI  - Successful prior treatment with dasatinib followed by stem cell transplantation
      in a patient with CML in blastic crisis with a BCR-ABL mutation.
AB  - We report a case of imatinib- and nilotinib-resistant Ph-positive chronic myeloid
      leukemia (CML) in blast crisis in which successful pretreatment with dasatinib
      with cord blood transplantation resulted in molecular remission. Before dasatinib
      therapy, the patient was found to have a F359V BCR-ABL mutation. He was treated
      with dasatinib for just 16, 19 days before allogeneic stem cell transplantation.
      This successful case indicates that reduction of tumor burden by second
      generation tyrosine kinase inhibitors, in combination with stem cell
      transplantation, might be effective to treat CML, even in the advanced phase.

PMID- 20047108
TI  - Ludwig Haberlandt--"Grandfather of the Pill".

PMID- 20047100
TI  - Effects of superior colliculus ablation on the air-righting reflex in the rat.
AB  - To examine how the superior colliculus, the motor center of orientation and
      avoidance, could interact with postural reflexes, we investigated effects of
      unilateral and bilateral ablations on air-righting reflex movements in otherwise
      intact rats. Superior colliculus ablations variously modified righting movements:
      After falling from the supine position, the rats sometimes showed dorsiflexion
      instead of normal ventriflexion; the motor sequence of rotation from the fore- to
      the hindquarter was often modified to simultaneous rotation; lateral turn from
      supine to prone position was occasionally insufficient; body direction that was
      normally kept constant during falling was often changed; final posture sometimes
      deviated from the horizontal position. The first three abnormalities occurred
      almost twice in frequency as lesions increased from unilateral to bilateral
      ablation, and in unilaterally ablated rats, did so in righting contraversive to
      the lesions. Multiple influences of tectoreticular input to the air-righting
      reflex center are discussed.

PMID- 20047109
TI  - [Challenges in acute stroke].

PMID- 20047111
TI  - A chestnut frier with burn wounds on his fingers.

PMID- 20047112
TI  - Ludwig Haberlandt--A pioneer in hormonal contraception.
AB  - Ludwig Haberlandt (1 February 1885 - 22 July 1932), pioneer in hormonal
      contraception, was born in Graz, where he graduated from the university in 1909
      in medicine summa cum laude and began his career as a physiologist. The idea of
      temporary hormonal contraception in the female body entered his mind in February
      1919, when he was already Professor of Physiology in Innsbruck. He pursued his
      project ambitiously and by 1921 demonstrated temporary hormonal contraception in
      a female animal by transplanting ovaries from a second, pregnant, animal. From
      1923, after further successful scientific work in this field, he began
      highlighting the importance of clinical trials in presentations. From then, he
      was criticized by his colleagues, who accused him of hindering unborn life. His
      idea was contradictory to the moral, ethic, religious and political agendas of
      that time in Europe. In 1927 official reports escalated, his family was
      ostracized by the local population, and Ludwig Haberlandt refused any further
      interviews. Against all opposition, in 1930 he began clinical trials after
      successful production of a hormonal preparation, Infecundin, by the G. Richter
      Company in Budapest, Hungary. Although at the peak of his scientific career, he
      was unable to pursue other scientific agendas because of the disputed
      contraception project. After he committed suicide, on 22 July 1932, scientific
      discussion about hormonal contraception ceased until 1970 when scientists began
      referring to his earlier medical and scientific work.

PMID- 20047110
TI  - Innate immune dysfunction in acute and chronic liver disease.
AB  - Liver cirrhosis is a common disease causing great public-health concern because
      of the frequent complications requiring hospital care. Acute liver failure is
      also prone to several complications but is rare. One of the main complications
      for both acute and chronic liver diseases is infection, which regularly causes
      decompensation of cirrhosis, possibly leading to organ failure and death. This
      review focuses on innate immune function in cirrhosis, acute-on-chronic liver
      failure and acute liver failure. The known defects of Kupffer cells, neutrophils
      and monocytes are discussed, together with the pathophysiological importance of
      gut permeability, portal hypertension and intrinsic cellular defects, and the
      role of endotoxin, albumin, lipoproteins and toll-like receptors. Based on these
      different pathomechanisms, the available information on therapeutic strategies is
      presented. Antibiotic and probiotic treatment, nutritional support, artificial
      liver support, and experimental strategies such as inhibition of toll-like
      receptors and use of albumin and colony-stimulating factors are highlighted.

PMID- 20047113
TI  - [Implementation of thrombolysis in acute stroke--10-year results of the Innsbruck
      stroke registry].
AB  - BACKGROUND: Randomized controlled trials have yielded evidence for the efficacy
      and safety of intravenous alteplase in the therapy of acute ischemic stroke. A
      large patient registry has recently confirmed the safe implementation of this
      therapy in the clinical routine setting. METHODS: Between January 1998 and
      December 2007 302 stroke patients were treated with 0.9 mg/kg rt-PA at the stroke
      unit of the Innsbruck University Hospital. Severity and circumstances of the
      stroke event, indicators of pre- and intrahospital management as well as safety
      and outcome at three months were prospectively assessed in the local thrombolysis
      database. RESULTS: The number of patients receiving intravenous thrombolysis
      increased continuously from 2 patients in 1998 to 67 in 2007 and 87 patients in
      2008. 43% of our patients were females. The median age and NIHSS-score on
      admission was 67 and 16, respectively. The mean onset-to-needle time decreased
      from 171 min to 110 min--mainly due to a substantial shortening of the door-to
      needle time from 105 min to 45 min. A proportion of 41% of our patients were
      treated in the main working time while 59% received rt-PA during night and
      weekend service. A total of 38% of our patients were functionally independent at
      three months (mRS 0-2). Once considering the high initial stroke severity in our
      patient series and correcting the NIHSS scores to levels usually seen in
      randomized control trials and patient registries, 56% of our patients would reach
      a good outcome (mRS 0-2). The rate of symptomatic intracranial bleedings was low
      at 6.3%. CONCLUSION: Our data reinforce that intravenous thrombolysis is safe in
      the treatment of acute ischemic stroke in clinical routine setting. Establishment
      of modern stroke services and the implementation of structural operating
      procedures have contributed to an increase in the number of treated patients and
      a parallel decrease in door-to-needle time at our hospital. Widespread
      educational programs in the general community, introduction of optimized pre
      hospital triage algorithms as well as the potential extension of the 3-hour
      window to 4.5 hours all are suitable measures to further extend the benefit of
      i.v. thrombolysis to large proportion of stroke patients.

PMID- 20047114
TI  - Efficacy of systematic endurance and resistance training on muscle strength and
      endurance performance in elderly adults--a randomized controlled trial.
AB  - BACKGROUND: Aging is associated with loss in both muscle mass and the metabolic
      quality of skeletal muscle. A major part of these changes is associated with an
      age-related decrease in the level of physical activity and may be counteracted by
      endurance training (ET) and resistance training (RT). OBJECTIVE: Since both
      muscle strength and aerobic power decrease with age, we investigated what form of
      training might be best for improvements in physical performance in the elderly.
      In detail, we wanted to know whether systematic ET can augment muscle strength
      and/or whether systematic RT can augment the aerobic power of healthy elderly
      adults. METHODS: Forty-two volunteers (32 women, 10 men) were recruited for the
      study and randomized into three groups: 13 persons undertook a continuous 6-month
      ET program, 15 undertook a continuous 6-month RT program and 14 served as a
      control group. All persons performed a cycling test to measure aerobic power
      (VO(2max)) and maximum workload (W(max)) before and after the training period.
      Maximum strength was determined from one repetition maximum (1-RM). RESULTS:
      After 6 months of RT, maximum strength increased by an average of 15% for leg
      press (P < 0.01), 25% for bench press (P < 0.01) and 30% for bench pull (P <
      0.001); ET showed no effect on maximum strength except for the 1-RM in bench
      pull. Aerobic power improved by 6% in the ET group and by 2.5% in the RT group,
      neither of which was significant. Maximum workload improved significantly by 31%
      in the ET group (P < 0.001) and by 6% in the RT group (P = 0.05). ET resulted in
      a significant 5.3% reduction of body fat (P < 0.05), whereas only RT increased
      lean body mass by 1.0 +/- 0.5 kg. CONCLUSION: RT leads to a genuine increase in
      lean body mass and muscle strength in healthy elderly adults and is therefore the
      best method for treatment of amyotrophia. ET appears to be the most efficacious
      training mode for maintaining and improving maximum aerobic power in the elderly
      and should be viewed as a complement to RT. The loading intensity to promote
      hypertrophy should approach 60-80% of 1-RM with an exercise volume ranging from 3
      to 6 sets per muscle group per week of 10-15 repetitions per exercise. ET should
      be performed on two days per week controlled by a heart rate according to 60% of
      VO(2max) and an exercise volume ranging from 30 to 60 minutes per week.

PMID- 20047116
TI  - Ischemic stroke associated with adenoviral infection in a 4-year-old boy.
AB  - We present a case of childhood arterial ischemic stroke associated with proven
      adenoviral upper respiratory tract infection in a previously healthy 4-year-old
      boy. Adenoviral meningitis and encephalitis have been reported repeatedly, thus
      confirming the neuroinvasive capability of these viruses. However, an association
      between adenoviral infection and arterial ischemic stroke has not been described
      thus far. HIV and varicella zoster virus are the only microorganisms that have
      been consistently associated with arterial ischemic stroke in the absence of
      acute central nervous system infection. In HIV-infected individuals ischemic
      stroke can be caused by vasculitis and hypercoagulability. Granulomatous
      arteritis of the vessel wall causes post-varicella cerebral infarction and
      ischemic stroke after herpes zoster ophthalmicus. We suggest that in our patient
      a post-varicella cerebral infarction-like mechanism of adenoviral spread to the
      affected artery wall occurred through the ophthalmic branch of the trigeminal
      nerve. Adenoviruses are neuroinvasive and inflamed conjunctiva might have
      permitted introduction of the virus into ophthalmic nerve tissue. In consequence,
      the stenotic lesion of the artery might have been induced by the presence of
      adenovirus and the subsequent inflammatory reaction. We recommend a prompt quest
      for adenoviral infection in all previously healthy children with fever and
      clinical presentation compatible with ischemic stroke, because timely diagnosis
      and treatment could improve the outcome and hasten neurological recovery.

PMID- 20047115
TI  - Nephro- and neuroprotective effects of rosiglitazone versus glimepiride in
      normoalbuminuric patients with type 2 diabetes mellitus: a randomized controlled
      trial.
AB  - BACKGROUND: Thiazolidinediones represent a novel class of drugs that exert
      pleiotropic effects at various levels and lower blood glucose through reduction
      of insulin resistance in patients with type 2 diabetes mellitus. MAIN PURPOSE:
      The nephro- and neuroprotective effects of rosiglitazone vs. glimepiride were
      evaluated in normoalbuminuric patients with type 2 diabetes mellitus. The
      relevance of several biomarkers in the diagnosis of incipient diabetic
      nephropathy and cerebral microangiopathy was also assessed. METHODS: A total of
      34 normoalbuminuric patients with type 2 diabetes mellitus were enrolled in a 1
      year open-label randomized controlled trial. Group A comprised 17 patients (7
      men, 10 women, mean age 63 +/- 8.07 years) treated with rosiglitazone plus
      metformin; Group B comprised 17 patients (7 men, 10 women, mean age 63.2 +/- 7.19
      years) treated with glimepiride plus metformin. All patients were assessed at
      initiation, at 6 months and by the end of the study concerning serum and urinary
      beta2-microglobulin, urinary a1-microglobulin, serum cystatin C, serum
      creatinine, glomerular filtration rate, C-reactive protein, fibrinogen, glycated
      hemoglobin, cholesterol, triglycerides, hemoglobin, and the urinary
      albumin/creatinine ratio (UACR). Cerebral hemodynamic parameters were also
      measured: pulsatility index and resistance index in the internal carotid artery
      and middle cerebral artery, and intima-media thickness in the common carotid
      artery. RESULTS: At 1 year there were differences between groups A and B
      regarding serum cystatin C (P < 0.04), urinary beta2-microglobulin (P < 0.004),
      urinary a1-microglobulin (P < 0.0001), C-reactive protein (P < 0.0001),
      fibrinogen (P < 0.0001), serum creatinine (P < 0.0024), glomerular filtration
      rate (P < 0.0010), UACR (P < 0.0001), and the cerebral hemodynamic indices. The
      increase in a1- and beta2-microglobulin preceded the occurrence of
      microalbuminuria. UACR correlated with urinary a1- microglobulin (r = 0.4854),
      urinary beta2-microglobulin (r = 0.4867), and serum cystatin C (r = 0.3702). The
      cerebrovascular parameters improved in group A vs. group B and correlated with
      urinary beta2- and a1-microglobulin, C-reactive protein, fibrinogen, glomerular
      filtration rate, and duration of diabetes. CONCLUSION: Rosiglitazone demonstrated
      its nephro- and neuroprotective effects in normoalbuminuric patients with type 2
      diabetes mellitus by the end of the follow-up period and these effects were
      beyond glycemic control. Urinary beta2- and a1-microglobulin are significant
      biomarkers for incipient diabetic nephropathy and diabetic cerebral
      microangiopathy. These biomarkers showed that proximal tubule dysfunction may
      develop before the stage of microalbuminuria.

PMID- 20047117
TI  - Gastrointestinal stromal tumors: Recommendations on diagnosis, therapy and follow
      up care in Austria.
AB  - Adequate treatment of gastrointestinal stromal tumors (GISTs) is linked to an
      interdisciplinary treatment approach. Austrian representatives of medical
      oncology, surgery, pathology, radiology and gastroenterology have issued this
      consensus manuscript within the context of currently available and published
      literature. The paper contains guidelines and recommendations for diagnosis,
      therapy and follow-up of GIST patients in Austria.

PMID- 20047119
TI  - Therapeutic factors considered according to the preoperative splenic volume for a
      prolonged increase in platelet count after partial splenic embolization for liver
      cirrhosis.
AB  - PURPOSE: Infarcted splenic volume has been identified as the predictive factor
      for a prolonged increase in platelet count after partial splenic embolization
      (PSE). However, despite enough infarcted splenic volume, some patients show only
      a slight increase in platelet counts after PSE because of rapid regrowth of the
      noninfarcted splenic parenchyma within several months post-PSE. The purpose of
      this study was to determine the therapeutic factors based on the preoperative
      splenic volume for a prolonged increase in platelet counts after PSE. METHODS: In
      72 cirrhotic patients with follow-ups longer than 1 year post-PSE, depending on
      the preoperative splenic volume, the splenic factors associated with a prolonged
      increase in platelet counts at 1 year after PSE were retrospectively examined.
      RESULTS: In 57 patients with preoperative splenic volumes <or=700 ml, the
      preoperative splenic volume (P = 0.001), infarcted splenic volume (P < 0.001),
      and splenic infarction ratio (P = 0.001) showed positive correlations with
      increments in platelet counts at 1 year post-PSE. In 15 patients with
      preoperative splenic volumes >700 ml, noninfarcted splenic volume (P = 0.003) and
      splenic infarction ratio (P = 0.002) showed negative and positive correlations
      with the increment in platelet counts at 1 year post-PSE, respectively.
      CONCLUSIONS: In patients with splenic volumes <or=700 ml, the infarcted splenic
      area significantly affects the prolonged increase in platelet counts post-PSE. In
      patients with splenic volumes >700 ml, the noninfarcted splenic area is
      significant.

PMID- 20047121
TI  - Can an incomplete stent expansion modulate the effects of TIPS?

PMID- 20047122
TI  - Gastrointestinal stromal tumor: a bridge between bench and bedside.
AB  - Gastrointestinal stromal tumor (GIST) is considered to be driven by a gain-of
      function mutation in the KIT or PDGFRA gene. Cure can be obtained only by
      complete surgical removal of the GIST; however, imatinib, an inhibitor of KIT and
      PDGFRA, is indicated for advanced, recurrent, and/or metastatic GISTs. Imatinib
      exhibited remarkable clinical effects on advanced GISTs, with substantial
      tolerability. Its efficacy greatly depends on the genotype of GIST. The drug,
      however, met intrinsic or acquired resistance during the treatment, of which the
      molecular mechanisms were mostly dependent on the genotype of GIST, including
      primary mutations or secondary mutations in the kinase domains of the
      corresponding target genes, respectively. Although sunitinib had substantial
      effects on imatinib-resistant GIST, this drug also encountered primary or
      secondary resistance depending on the genotype. Thus, advanced GIST may require
      multidisciplinary treatment. Because resistance mechanisms show some regularity,
      it is hoped that, in the near future, we may be able to develop a new drug to
      which resistance does not occur easily, based on scientific evidence.

PMID- 20047123
TI  - Current understanding of SPEM and its standing in the preneoplastic process.
AB  - Gastric cancer is the second leading cause of cancer-related death worldwide, but
      the details of gastric carcinogenesis remain unclear. In humans, two
      preneoplastic metaplasias are associated with the precancerous stomach:
      intestinal metaplasia and spasmolytic polypeptide-expressing metaplasia (SPEM).
      While mouse models of Helicobacter sp. infection have not shown intestinal
      metaplasia, a number of mouse models lead to the evolution of SPEM. In this
      review, we summarize increasing data that indicates that SPEM arises in the
      setting of parietal cell loss, either following acute druginduced oxyntic atrophy
      or in chronic oxyntic atrophy associated with H. felis infection. Importantly,
      recent investigations support the origin of SPEM through transdifferentiation
      from mature chief cells following parietal cell loss. Novel biomarkers of SPEM,
      such as HE4, hold promise as specific markers of the metaplastic process distinct
      from normal gastric lineages. Staining with HE4 in humans and other studies in
      gerbils suggest that SPEM arises initially in the human stomach following
      parietal cell loss and then further evolves into intestinal metaplasia, likely in
      association with chronic inflammation. Further studies are needed to broaden our
      knowledge of metaplasia and early cancer-specific biomarkers that could give
      insights into both lineage derivation and preneoplasia detection.

PMID- 20047124
TI  - Association between dietary heterocyclic amine levels, genetic polymorphisms of
      NAT2, CYP1A1, and CYP1A2 and risk of stomach cancer: a hospital-based case
      control study in Japan.
AB  - BACKGROUND: Although the associations between grilled (broiled) or barbecued
      meats or fish intake and stomach cancer risk have been investigated, the evidence
      implicating heterocyclic amine (HCA) intake as a cause of stomach cancer is
      limited. We conducted a case-control study to investigate the association between
      HCA intake and stomach cancer risk. We also investigated the possible effect of
      genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on stomach cancer. METHODS: HCA
      exposure data were assessed using a self-administered food-frequency
      questionnaire, and estimated HCA intake was verified by measuring 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values in human hair. A total of 149
      cases and 296 controls were included in the analyses. Odds ratios (ORs) were
      calculated, using conditional logistic regression analysis, to compare intake
      levels between the first and third tertiles. RESULTS: Results showed no
      statistically significant increase in the risk of stomach cancer with respect to
      total HCA intake (OR, 1.11; 95% confidence interval [CI], 0.36, 3.49), or with
      respect to the intake of individual HCAs; namely, PhIP, 2-amino-3, 4
      dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx). Genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not
      influence the association of HCA intake with stomach cancer. CONCLUSION: In the
      present study, with a limited sample size of subjects with low HCA exposure, no
      association was found between HCA intake and stomach cancer, nor was there any
      evidence of any influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on
      the risk of stomach cancer.

PMID- 20047125
TI  - Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer
      refractory to fluorouracil, irinotecan, and cisplatin.
AB  - BACKGROUND: Although triweekly administration of paclitaxel is approved for
      gastric cancer in Japan, currently, the drug is often delivered with a weekly
      schedule because of the equivalent efficacy and lesser toxicity of this dosing
      schedule as compared with the triweekly administration schedule. Weekly
      administration of paclitaxel as second-line or first-line chemotherapy for
      gastric cancer has been reported to yield a response rate of about 20%. Because
      there has been no report of the efficacy of weekly paclitaxel in the third-line
      setting, this retrospective study investigated the efficacy and toxicities of
      weekly paclitaxel used in the third-line setting for the treatment of gastric
      cancer refractory to all three key drugs, fluorouracil, irinotecan, and
      cisplatin, used in clinical practice. METHODS: In 85 patients with advanced or
      recurrent histologically confirmed gastric adenocarcinoma who had failed to
      respond to prior chemotherapy regimens containing fluorouracil, irinotecan, and
      cisplatin, paclitaxel (80 mg/m(2)) was administered weekly, three times, for 3
      weeks out of 4. RESULTS: The median number of courses was 3 (range, 1-38). The
      overall response rate was 23.2% (19/82) in the patients with measurable lesions,
      and ascites disappeared in 15 of 48 patients (31.3%). Progression-free survival
      was 105 days and the median survival time was 201 days from the initiation of
      paclitaxel administration. Grade 3 or 4 leukopenia, neutropenia, anemia, and
      thrombocytopenia were observed in 25 (29%), 25 (29%), 37 (44%), and 3 (4%)
      patients. Other, nonhematological, toxicities were nausea, vomiting, anorexia,
      sensory neuropathy, fatigue, and febrile neutropenia. CONCLUSION: Weekly
      paclitaxel administration shows activity against advanced gastric cancer also in
      the third-line setting.

PMID- 20047126
TI  - A phase II study of doxifluridine and docetaxel combination chemotherapy for
      advanced or recurrent gastric cancer.
AB  - BACKGROUND: The aim of this study was to establish the efficacy and safety of
      doxifluridine and docetaxel for patients with advanced or recurrent gastric
      cancer. METHODS: The regimen consisted of oral administration of doxifluridine
      533 mg/m(2) per day on days 1-14 and an intravenous infusion of docetaxel 50
      mg/m(2) on day 8. The primary endpoint was the overall response rate. The
      secondary endpoints were overall survival, progression-free survival, and
      toxicities. RESULTS: Between June 2004 and December 2006, a total of 40 eligible
      patients were enrolled in this study. Seven of them showed a partial response,
      with an overall response rate of 17.5%. The response rate was 18.8% in 32
      patients with refractory tumors. The median progression-free survival time and
      the median overall survival time were 2.6 months and 12.7 months, respectively,
      in all 40 patients; and 2.6 months and 14.0 months, respectively, in the 32
      patients with refractory tumors. Grade 3/4 hematological toxicity included
      neutropenia in 52.5%, leukocytopenia in 17.5%, and febrile neutropenia in 7.5%.
      Grade 3 or more nonhematological toxicities were infrequent. CONCLUSION: The
      combination chemotherapy of doxifluridine and docetaxel was well tolerated and
      relatively effective when used as a second-line chemotherapy for advanced or
      recurrent gastric cancer.

PMID- 20047127
TI  - Analysis of the color patterns of early gastric cancer using an autofluorescence
      imaging video endoscopy system.
AB  - BACKGROUND: Using a novel autofluorescence imaging video endoscopy system (AFI),
      tumors in the esophagus and the colon appeared purple in a green background, but
      the color patterns of early gastric cancer (EGC) were found to vary. Factors
      associated with these patterns remain unknown. The aims of the present study were
      to classify the color patterns of EGCs and to investigate the correlation between
      the patterns and clinicopathological features. METHODS: A total of 107 EGCs that
      had been evaluated by AFI endoscopy, prior to endoscopic or surgical resection,
      were included. The color patterns of EGCs in AFI images and the association
      between tumor color and clinicopathological factors were evaluated. These factors
      included tumor morphology, location, size, background color, histological type,
      depth of invasion, lymphatic or vessel permeation, and ulceration. RESULTS: The
      color patterns of EGCs were classified into the following four groups: purple
      tumors in a green background (52%); green tumors with a purple margin in a green
      background (21%); green tumors in a purple background (17%); and purple tumors in
      a purple background (10%). Univariate analysis showed that macroscopic type,
      histological type, ulceration, and background AFI color were significantly
      associated with tumor color, whereas multivariate analysis revealed that
      macroscopic type was the only independent contributor to tumor color. CONCLUSION:
      The present study has enabled a clearer understanding of the significance of
      tumor color in relation to the AFI imaging of EGCs. Recognition of the color
      patterns in AFI images should help in the diagnosis of EGCs.

PMID- 20047128
TI  - Gastric schwannoma exhibiting increased fluorodeoxyglucose uptake.
AB  - This is the first case of gastric schwannoma that exhibited increased
      accumulation of [(18)F] fluorodeoxyglucose (FDG) on positron emission tomography
      (PET) imaging. The patient was a 60-year-old woman in whom
      esophagogastroduodenoscopy showed a submucosal tumor, about 25 mm in size, in the
      upper body of the stomach, with ulceration at the top of the tumor. Endoscopic
      ultrasonography revealed a well-defined hypoechoic mass located in the proper
      muscle layer of the stomach. The specimen taken from the tumor showed only
      inflammatory degenerative tissue. Abdominal computed tomography revealed a tumor
      in the upper body of the stomach. FDG-PET showed FDG uptake (standardized uptake
      value [SUV] max 5.8) coincident with the tumor. Hence, the tumor was diagnosed
      initially as a gastrointestinal stromal tumor of the stomach. Laparoscopic
      partial gastrectomy was performed. Pathological examination showed that the tumor
      consisted of spindle cells with large nuclei, and mitosis was absent. The Ki-67
      labeling index of the tumor cells was 4%. Immunohistochemically, the tumor cells
      showed a positive reaction for S-100 protein, whereas they were negative for KIT,
      CD 34, and alpha-smooth muscle actin protein. The tumor was diagnosed as a benign
      gastric schwannoma. Gastric schwannoma should be included in the differential
      diagnosis of submucosal tumors of the stomach with FDG uptake.

PMID- 20047129
TI  - Insulin resistance in chronic hepatitis C: mechanisms and clinical relevance.
AB  - Insulin resistance is the main clinical and pathogenetic feature of the metabolic
      syndrome, one of the major health problems worldwide. Chronic liver diseases may
      induce insulin resistance. The hepatic manifestation of the metabolic syndrome is
      nonalcoholic fatty liver disease. Insulin promotes the storage of energy in the
      fed state by stimulation of glycogen synthesis, lipogenesis, suppression of
      gluconeogenesis and VLDL formation. Epidemiological studies have shown that
      chronic hepatitis C induces insulin resistance. Insulin resistance in chronic
      hepatitis C is associated with progression of liver fibrosis, resistance to
      antiviral therapy and development of hepatocellular carcinoma. Here we review the
      major findings from epidemiological studies from 1994 to the present which have
      resulted in our current knowledge of insulin resistance in chronic hepatitis C.
      We further summarise the preliminary pathogenetic models that explain the
      development of hepatitis C virus-induced insulin resistance. Finally, we draw
      conclusions for the clinical management of these patients.

PMID- 20047130
TI  - Outpatient treatment of pulmonary embolism.
AB  - Pulmonary embolism (PE) is traditionally treated in hospital. Growing evidence
      from non randomized prospective studies suggests that a substantial proportion of
      patients with non-massive PE might be safely treated in the outpatient setting
      using low molecular weight heparins. Based on this evidence, professional
      societies started to recommend outpatient care for selected patients with non
      massive PE. Despite these recommendations, outpatient treatment of non-massive PE
      appears to be uncommon in clinical practice. The major barriers to PE outpatient
      care are, firstly, the uncertainty as how to identify low risk patients with PE
      who are candidates for outpatient care and secondly the lack of high quality
      evidence from randomized trials demonstrating the safety of PE outpatient care
      compared to traditional inpatient management. Also, although clinical prognostic
      models, echocardiography and cardiac biomarkers accurately identify low risk
      patients with PE in prospective studies, the benefit of risk stratification
      strategies based on these instruments should be demonstrated in prospective
      management studies and clinical trials before they can be implemented as decision
      aids to guide PE outpatient treatment. Before high quality evidence documenting
      the safety of an outpatient treatment approach is published, outpatient
      management of non-massive PE cannot be generally recommended.

PMID- 20047131
TI  - Myocardial contrast echocardiography for the distinction of hypertrophic
      cardiomyopathy from athlete's heart and hypertensive heart disease.
AB  - BACKGROUND: Myocardial contrast echocardiography (MCE) is able to measure in vivo
      relative blood volume (rBV, i.e., capillary density), and its exchange frequency
      b, the constituents of myo-cardial blood flow (MBF, ml min-1 g-1). This study
      aimed to assess, by MCE, whether left ventricular hypertrophy (LVH) in
      hypertrophic cardiomyopathy (HCM) can be differentiated from LVH in triathletes
      (athlete's heart, AH) or from hypertensive heart disease patients (HHD). METHODS:
      Sixty individuals, matched for age (33 +/- 10 years) and gender, and subdivided
      into four groups (n = 15) were examined: HCM, AH, HHD and a group of sedentary
      individuals without LVH (S). rBV (ml ml-1), b (min-1) and MBF, at rest and during
      adenosine-induced hyperaemia, were derived by MCE in mid septal, lateral and
      inferior regions. The ratio of MBF during hyperaemia and MBF at rest yielded
      myocardial blood flow reserve (MBFR). RESULTS: Septal wall rBV at rest was lower
      in HCM (0.084 +/- 0.023 ml ml-1) than in AH (0.151 +/- 0.024 ml ml-1, p <0.01)
      and in S (0.129 +/- 0.026 ml ml-1, p <0.01), but was similar to HHD (0.097 +/-
      0.016 ml ml-1). Conversely, MBFR was lowest in HCM (1.67 +/- 0.93), followed by
      HHD (2.8 +/- 0.93, p <0.01), by S (3.36 +/- 1.03, p <0.001) and by AH (4.74 +/-
      1.46, p <0.0001). At rest, rBV <0.11 ml ml-1 accurately distinguished between HCM
      and AH (sensitivity 99%, specificity 99%), similarly MBFR < or =1.8 helped to
      distinguish between HCM and HHD (sensitivity 100%, specificity 77%). CONCLUSIONS:
      rBV at rest, most accurately distinguishes between pathological LVH due to HCM
      and physiological, endurance-exercise induced LVH.

PMID- 20047133
TI  - Innate immunity against retroviral pathogens: from an ambiguous genetic self to
      novel therapeutic approaches.
AB  - Almost half of the human genome is derived from exogenous genetic invaders, most
      of them related to retroviruses. This is the consequence of longstanding
      interactions between retroelements and higher organisms, governed by a delicate
      equilibrium between virus-based evolutionary forces and control by host defense
      mechanisms. Insight into these longstanding genetic conflicts is suggesting leads
      for novel therapeutic strategies to fight HIV infection. In 2001, the Human
      Genome Organisation (HUGO) and the Human Genome Project (HGP) consortia provided
      first drafts of the sequence of the human genome. Completed in 2004, this effort
      opened new avenues for understanding the genetic bases of both physiological and
      pathological process, hence to move towards a more global comprehension of health
      and disease. As insights into the content of the human genome were gained, it
      quickly became apparent that only a fraction, barely two percent, encodes for
      proteins, which had been traditionally considered as the main executive arms of
      the cell. More strikingly even, close to 50 percent of human DNA was found to
      derive from genetic invaders called transposons, most of them retroelements
      functionally related to the human immunodeficiency virus (HIV). Found in the
      genomes of all species, transposons are motors of evolution, yet their
      uncontrolled spread can be fatal to their host organisms. Their presence in
      higher species thus reflects a delicate equilibrium between occasional
      permissiveness and tight restriction, through innate immunity mechanisms also
      engaged in protection against their exogenous viral counterparts.

PMID- 20047132
TI  - Pulse oximetry screening for congenital heart defects in Switzerland: most but
      not all maternity units screen their neonates.
AB  - QUESTIONS: In Switzerland, the screening of neonates for congenital heart defects
      (CHD) by using pulse oximetry (PO) on the first day of life was recommended in
      2005. We assessed the current practice of Swiss maternity units regarding PO
      screening to define the actual screening rate in Switzerland and to detect
      possible difficulties in the implementation of this screening. METHODS: This
      descriptive study was conducted by means of a standardized questionnaire that was
      sent to all Swiss maternity units. RESULTS: The response rate was 100%. 76% of
      the units perform regular PO screening and, on the basis of the number of births
      for 2007, this means that 85% of newborns in Switzerland undergo screening.
      Although units which do not perform PO screening include every category of
      maternity unit, the screening is performed to a significantly lower extent in
      birthing centres than in hospitals (p <0.001). The number of unscreened neonates
      was 5398 within small units (<1000 births per year) while it was 6137 within
      large units (>1000 births per year). The main reasons for not performing PO
      screening are financial factors and the belief that clinical signs are sufficient
      for the detection of CHD. CONCLUSIONS: Greater effort is needed to implement a
      nationwide PO screening program for CHD. Special attention should be paid to
      birthing centres given their limited capacity to treat newborns with critical
      CHD.

PMID- 20047134
TI  - Molecular autopsy in sudden cardiac death and its implication for families:
      discussion of the practical, legal and ethical aspects of the multidisciplinary
      collaboration.
AB  - Sudden cardiac death (SCD) is a major cause of premature death in young adults
      and children in developed countries. Standard forensic autopsy procedures are
      often unsuccessful in determining the cause of SCD. Post-mortem genetic testing,
      also called molecular autopsy, has revealed that a non-negligible number of these
      deaths are a result of inherited cardiac diseases, including arrhythmic disorders
      such as congenital long QT syndrome and Brugada syndrome. Due to the heritability
      of these diseases, the potential implications for living relatives must be taken
      into consideration. Advanced diagnostic analyses, genetic counselling, and
      interdisciplinary collaboration should be integral parts of clinical and forensic
      practice. In this article we present a multidisciplinary collaboration
      established in Lausanne, with the goal of properly informing families of these
      pathologies and their implications for surviving family members. In Switzerland,
      as in many other countries, legal guidelines for genetic testing do not address
      the use of molecular tools for post-mortem genetic analyses in forensic practice.
      In this article we present the standard practice guidelines established by our
      multidisciplinary team.

PMID- 20047135
TI  - Genetic polymorphisms of GSTP1 related to response to 5-FU-oxaliplatin-based
      chemotherapy and clinical outcome in advanced colorectal cancer patients.
AB  - OBJECTIVE: To determine whether genetic polymorphisms of GSTP1 Ile105Val (A-->G)
      predict chemosensitivity and clinical outcome in patients with advanced
      colorectal cancer, treated by 5-FU/oxaliplatin-based chemotherapy. METHODS: In
      this retrospective study, the population consisted of 122 advanced colorectal
      cancer patients (III stage 51, IV stage 71). Patients were treated with 5-FU
      oxaliplatin-based chemotherapy, and their response was evaluated after at least
      two cycles of treatments; all patients (122) were evaluated for median survival
      time (MST). GSTP1 genotypes were detected by TaqMan-MGB probe methods. RESULTS:
      75 patients (61.47%) were Ile/Ile genotype, 10 (8.2%) were Val/Val genotype, and
      37 (30.33%) were Ile/Val genotype. Patients possessing the glutathione S
      transferase P1-105 Val/Val genotype showed a response rate of 60.0% compared to
      25.89% in patients harboring at least one GSTP1-105 Ile allele (p = 0.032). GSTP1
      105 Val/Val patients demonstrated a significant superior median survival time of
      20.4 months (95% CI: 11.85 to 28.95) compared to 6.5 months (95% CI: 4.26 to
      8.74) in patients with 105 Ile/Ile genotype and 10.3 months (95% CI: 7.05 to
      13.55; p <0.01) in patients with GSTP1 105 Ile/Val genotype. CONCLUSION: The
      GSTP1 105Val/105Val genotype is associated with a higher clinical response rate
      to oxaliplatin-based chemotherapy and with increased survival of patients with
      advanced colo-rectal cancer, receiving 5-FU/oxaliplatin chemotherapy.

PMID- 20047136
TI  - H1N1 pandemic: watch out for the first wave in Switzerland.

PMID- 20047137
TI  - Is sugar consumption detrimental to health? A review of the evidence 1995-2006.
AB  - Many countries set quantitative targets for added sugars, justifying this by
      expressing concern about the likely impact of sugar on weight control, dental
      health, diet quality, or metabolic syndrome. This review considers whether
      current intakes of sugar are harmful to health, and analyses recent literature
      using a systematic approach to collate, rank, and evaluate published studies from
      1995-2006. Results from high quality obesity studies did not suggest a positive
      association between body mass index and sugar intake. Some studies, specifically
      on sweetened beverages, highlighted a potential concern in relation to obesity
      risk, although these were limited by important methodological issues. Diet
      adequacy appeared to be achieved across sugar intakes of 6 to 20% energy,
      depending on subject age. Studies on metabolic syndrome reported no adverse
      effects of sugar in the long-term, even at intakes of 40-50% energy. The evidence
      for colorectal cancer suggested an association with sugar, but this appeared to
      have been confounded by energy intake and glycemic load. There was no credible
      evidence linking sugar with attention-deficit, dementia, or depression. Regarding
      dental caries, combinations of sugar amount/frequency, fluoride exposure, and
      food adhesiveness were more reliable predictors of caries risk than the amount of
      sugar alone. Overall, the available evidence did not support a single
      quantitative sugar guideline covering all health issues.

PMID- 20047138
TI  - Wine oxidation and the role of cork.
AB  - The present review aims to show the state of the art of oxidation mechanisms
      occurring especially in white wines by taking into account knowledge from
      different fields in relation to the subject. It is therefore divided into three
      main parts. First, the mechanisms of oxidation relevant to white wine are
      discussed in the light of recent scientific literature. Next, the phenomenon of
      oxygen solubility in wine during the winemaking process, and in particular during
      bottling is stated theoretically as well as practically. Finally, the aspect of
      wine conservation after bottling is examined with respect to mass transfers which
      may occur through the closure, with a special emphasis on cork. Currently,
      specific physico-chemical properties still make cork closures the most important
      closure type used for the wine market, and especially for high quality wines.
      This final section will also include a review of studies performed on this
      subject, which have been analyzed in detail from a theoretical mass transfer
      point of view, in order to assess the extent to which the proposed scientific
      tools and the observed tendencies are relevant to progress in the understanding
      of the impact of this parameter on the behavior of a wine.

PMID- 20047139
TI  - Evidence-based review on the effect of normal dietary consumption of fructose on
      development of hyperlipidemia and obesity in healthy, normal weight individuals.
AB  - In recent years, there has been episodic speculation that an increase in
      consumption of fructose from foods and beverages is an underlying factor
      responsible for the relatively recent increase in obesity and obesity-related
      diseases such as diabetes. Reports in support of this hypothesis have been
      published, showing that concentrations of triglycerides (TG) are higher and
      concentrations of insulin and hormones associated with satiety are lower in
      animals following the ingestion of fairly large quantities of fructose, compared
      to other carbohydrates. However, results from human studies are inconsistent. A
      possible reason for the inconsistent results is that they are dependent on the
      particular study population, the design of the studies, and/or the amount of
      fructose administered. A systematic assessment of the strength and quality of the
      studies and their relevance for healthy, normal weight humans ingesting fructose
      in a normal dietary manner has not been performed. The purpose of this review was
      to critically evaluate the existing database for a causal relationship between
      the ingestion of fructose in a normal, dietary manner and the development of
      hyperlipidemia or increased body weight in healthy, normal weight humans, using
      an evidence-based approach. The results of the analysis indicate that fructose
      does not cause biologically relevant changes in TG or body weight when consumed
      at levels approaching 95th percentile estimates of intake.

PMID- 20047140
TI  - Response to "Health risks of genetically modified foods".

PMID- 20047142
TI  - Immunomodulatory therapies and the risk of opportunistic infections.

PMID- 20047143
TI  - hERG: protein trafficking and potential for therapy and drug side effects.
AB  - Drug-induced QT interval prolongation is associated with torsade de pointes
      arrhythmia and sudden cardiac death. Acquired long QT syndrome poses a
      significant liability in pharmaceutical drug development, and has resulted in
      drugs being recalled from the market. This off-target property is caused
      primarily by the inhibition of cardiac hERG K+ currents. As a result, guidelines
      were established by The International Conference on Harmonisation of Technical
      Requirements for Registration of Pharmaceuticals for Human Use (ICH) requiring
      the preclinical evaluation of direct hERG channel blockade and QT prolongation.
      This review discusses established, as well as newly discovered and currently
      under-recognized, pro-arrhythmic mechanisms that are associated with hERG protein
      trafficking. Defective hERG trafficking is a research area of intensive
      scientific activity, and the implementation of screening for this type of hERG
      liability should be considered in order to improve the risk assessment and
      detection of drug-associated cardiotoxicity in safety pharmacology.

PMID- 20047144
TI  - Functional consequences of mTOR inhibition.
AB  - TOR (target of rapamycin) is a serine-threonine protein kinase that is conserved
      across a diverse range of species from fungi to mammals. The signaling pathway
      that is anchored by TOR is also conserved across species. In mammals, mTOR
      integrates growth factor, amino acid, nutrient and energy sensing signals, and
      thus plays a major role in cell growth and proliferation, protein synthesis and
      autophagy. As a result of the pivotal role of mTOR in signaling, the aberrant
      regulation of mTOR has been implicated in several disease processes, including
      cancer, diabetes, ocular diseases and neurodegenerative disorders, as well as in
      lifespan extension. More recently, rapamycin (sirolimus) analogs that antagonize
      the mTOR signaling pathway have been approved for the treatment of several
      cancers. This review describes some recent advances in the understanding of mTOR
      signaling, with an emphasis on the functional consequences of mTOR inhibition and
      therapeutic intervention strategies.

PMID- 20047145
TI  - The biological effects of isoform-specific PI3-kinase inhibition.
AB  - The four isoforms of class I phosphatidylinositol-3-kinase (PI3K) were originally
      thought to be redundant in function; however, further research and new
      technologies have revealed that each subunit has distinct characteristics. In the
      past decade the number of PI3K inhibitors has increased from a few agents with
      unacceptable promiscuity and pharmacological properties, to a family of selective
      agents that are either progressing through experimental development or are in
      clinical trials. These agents, with two notable exceptions, target multiple
      members of the PI3K class I isoforms. As data become increasingly available, the
      concept that inhibiting a single PI3K isoform may offer improved therapeutic
      benefit, while eliminating the potentially negative effects of pan-isoform
      inhibition, is driving efforts to develop more specific inhibitors. However,
      questions remain regarding the best isoform to inhibit for maximum benefit in
      different pathological settings, and whether increased specificity may lead to a
      loss in efficacy as a result of isoform redundancy in some settings. This review
      discusses the current understanding of individual PI3K isoforms in physiology and
      pathological states, as well as the status of PI3K inhibitors in preclinical and
      clinical development.

PMID- 20047146
TI  - Interactions between traditional Chinese medicines and Western therapeutics.
AB  - Traditional Chinese medicine (TCM) is a holistic approach to health that attempts
      to bring the body, mind and spirit into harmony. TCM is an essential part of the
      healthcare system in several Asian countries, and is considered a complementary
      or alternative medical system in most Western countries. An integration of the
      traditional Chinese and Western systems of medicine has begun in multiple medical
      centers internationally, and there is increasing evidence that several herbs and
      combinations of herbs used in TCM impart important pharmacological effects. The
      number of databases and compilations of herbs, herbal formulations, phytochemical
      constituents and molecular targets is increasing, primarily because of the
      widespread use of TCM in combination with Western drugs. The continued popularity
      of herbal remedies worldwide suggests that evidence-based research in this field,
      as well as information regarding the potential efficacy and safety of
      phytochemical constituents in herbs and TCM formulations, are essential,
      particularly when TCM is used in combination with other drugs. Herb-drug
      interactions are similar to drug-drug interactions in terms of their effects on
      ADME properties. Improvements in the knowledge of the molecular targets and
      metabolic pathways, as well as of the synergistic and inhibitory effects
      associated with important phytochemicals from herbs and herbal formulations, will
      lead to the development of rational approaches for the safe combination of
      healthcare systems from different cultures.

PMID- 20047148
TI  - Cytochrome P450 proteins: retention and distribution from the endoplasmic
      reticulum.
AB  - Cytochrome P450 (CYP) is a large family of well-conserved integral membrane
      proteins localized primarily in the membrane of the endoplasmic reticulum (ER),
      where these enzymes metabolize a variety of both endogenous and exogenous
      compounds. It has become apparent that these microsomal CYP proteins are also
      present in other cellular compartments, such as the cell surface and in
      mitochondria, where the enzymes display catalytic activity toward CYP-specific
      substrates, in some cases with altered substrate specificity. CYP-drug adducts
      exposed at the cell surface are important mediators of idiosyncratic drug
      toxicities. Therefore, understanding the molecular mechanisms responsible for
      directing these microsomal CYPs to other, non-ER cellular compartments is
      important. These alternatively localized CYPs should be considered as possible
      drug targets and as important factors during drug discovery and development, as
      the detoxification capacity is lower in the compartments where such CYP proteins
      are located. This review discusses the mechanisms of intracellular CYP transport,
      and the implications of the presence of CYP proteins in extra-ER compartments for
      drug metabolism and toxicity.

PMID- 20047147
TI  - The role of metabolites in predicting drug-drug interactions: focus on
      irreversible cytochrome P450 inhibition.
AB  - The irreversible inhibition of cytochrome P450 (CYP) enzymes can cause
      significant drug-drug interactions (DDIs). The formation of metabolites is
      fundamental for the inactivation of CYP enzymes. Of the 19 CYP enzyme
      inactivators for which the mechanism of action has been established, 10 have
      circulating metabolites, which are on the metabolic pathway to inactivation of
      the CYP enzyme. Because inactivation of CYP enzymes usually requires multiple
      metabolic steps, the prediction of interactions between metabolites and CYPs in
      vivo may require complex models and the availability of data generated in vitro
      from each metabolite. Data discussed in this review suggest that circulating
      metabolites are more important in CYP inhibition in vivo than has been
      acknowledged.

PMID- 20047150
TI  - Roles of CD44 in chemical-induced liver injury.
AB  - CD44 has been identified as one of the adhesion molecules that regulate cell
      migration in inflamed tissue. The principal ligand of CD44 is hyaluronan, and
      CD44 is involved in the metabolism of this compound. Furthermore, an increasing
      quantity of evidence suggests that CD44 has various functions related to
      inflammatory disease. This review focuses on the potential roles of CD44 in the
      pathogenesis of chemical-induced liver injury and discusses some of the functions
      of this protein in pathological processes. The discovery that CD44 deficiency
      induces severe liver injury, (associated with an increase in hepatocyte
      apoptosis) rather than suppressing liver inflammation is summarized. These data
      suggest that targeted therapies against adhesion molecules should be monitored
      carefully to ensure that liver disease is not exacerbated by treatment.

PMID- 20047149
TI  - Drug targeting: learning from toxin entry and trafficking in mammalian cells.
AB  - A significant number of therapeutic targets reside inside cells and intracellular
      organelles. Therapeutics therefore must be able to gain access to cellular
      compartments, and be able to interact specifically with a given molecule to exert
      a desired effect. Many naturally occurring toxins perform such targeting with
      apparent ease, making them excellent paradigms for the delivery of therapeutics
      to the cell interior. By studying the mechanisms of cell entry, trafficking and
      modes of toxicity of these model delivery vectors, researchers can decipher how
      cells transport both endogenous molecules and exogenously applied therapeutics
      inside cells. Perhaps more importantly, the exploitation of cell binding and
      trafficking motifs could allow a therapeutic to target specifically, traffic
      within and escape from cellular compartments; in addition, toxic domains can be
      used to disrupt cell function specifically for therapeutic purposes. This review
      provides an overview of recent developments in the understanding of toxin
      targeting and trafficking, and discusses how these developments could result in
      opportunities for the design of more specific and efficient systems for
      therapeutic targeting.

PMID- 20047151
TI  - Challenges in the prediction and modeling of oral absorption and bioavailability.
AB  - To predict the performance of a drug following oral dosing, a thorough
      understanding of the dissolution, uptake and metabolism of the compound is
      required. In this review, approaches to in silico modeling of these processes are
      discussed. Although oral absorption, which is limited by dissolution and passive
      permeation, is to some extent predictable, bioavailability, which is influenced
      by first-pass metabolism in the intestines and liver, is much more difficult to
      predict. Much of the difficulty in predicting oral absorption and bioavailability
      is in the experimental quantification of solubility in the gastrointestinal tract
      lumen, membrane permeability, plasma protein binding, metabolism and active
      transport, rather than the formulating of the mathematical models.

PMID- 20047152
TI  - Factors affecting drug release from liposomes.
AB  - Liposomes are the most widely used nanocarrier systems in medicine. Common
      strategies for tumor-specific drug delivery using liposomes include the passive
      accumulation of liposomes that have an increased circulation half-life, which is
      possible as a result of the leakiness of tumor neovasculature, as well as the
      active targeting of liposomes using surface-bound ligands. However, such
      targeting of the nanocarrier is not effective if the encapsulated drug within the
      liposome is not released at the intended site. Drug release can be influenced by
      both the membrane composition of the liposome and the choice of drug. In addition
      to environmental triggers, such as low pH and the presence of particular enzymes,
      external stimuli such as heat or ultrasound have gained attention in the clinic.
      This review provides a summary of the various approaches to modifying drug
      release from liposomes.

PMID- 20047153
TI  - Recent advances in the understanding of drug-mediated infusion reactions and
      cytokine release syndrome.
AB  - Infusion reactions and cytokine release syndrome (CRS) are an emerging issue in
      drug development and are of particular importance with the development of new
      therapeutic proteins. Increasing concerns regarding patient safety require a
      better understanding of the mechanism involved and the development of novel
      methods for preventing and predicting such reactions and CRS. This review
      discusses developments during the past few years in understanding the mechanisms
      that cause infusion reactions and CRS, advances in approaches to prevent CRS, the
      reason why preclinical animal models are unreliable predictors of CRS, and new
      developments in the design and analysis of in vitro screening systems for the
      prediction of CRS.

PMID- 20047155
TI  - Drugs to treat fibromyalgia - the transatlantic difference.
AB  - Fibromyalgia is a disorder characterized by chronic widespread musculoskeletal
      pain and stiffness. In 2007, the US FDA approved pregabalin as the first drug
      indicated for the management of fibromyalgia. Within 18 months, the agency had
      also approved duloxetine and milnacipran for the same indication. However,
      although these drugs are already marketed in Europe for other indications, the
      European regulatory authorities recently rejected extending approval for these
      three drugs for the treatment of fibromyalgia. This editorial discusses the
      possible reasons for this 'transatlantic difference'.

PMID- 20047156
TI  - The tetrahydrobiopterin pathway and pain.
AB  - Novel approaches for treating chronic pain are required to address a widely
      recognized, yet largely underserved and unmet, clinical need. The recently
      discovered link between tetrahydrobiopterin (BH4) synthesis and pain in
      preclinical models and humans provides a promising new approach for treating
      neuropathic and other forms of chronic pain. The rate-limiting enzyme in BH4
      synthesis, guanosine triphosphate cyclohydrolase 1 (GCH1), and sepiapterin
      reductase (SPR) are both promising drug targets based on initial active-site
      characterization of the SARs of these two enzymes. Reducing the elevated BH4
      levels associated with pain to baseline, while maintaining sufficient BH4 levels
      to limit side effects is the goal of discovery programs for novel therapeutics
      targeting GCH1 or SPR.

PMID- 20047157
TI  - COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence.
AB  - Antidepressant and antipsychotic drugs, predominantly serotonin and/or
      norepinephrine reuptake inhibitors and dopamine D2-antagonizing antipsychotic
      compounds, have several limitations. In addition, the exact pathophysiological
      mechanism leading to serotonergic, noradrenergic and dopaminergic dysfunction in
      psychotic disorders remains unclear. It has been postulated that an inflammatory
      mechanism may be involved in the pathogenesis of both depression and psychotic
      disorders. Furthermore, the differential activation of the enzyme indoleamine 2,3
      dioxygenase (IDO) and of the tryptophan/kynurenine metabolic pathway, resulting
      in the increased production of kynurenic acid in schizophrenia, and a possible
      increase in quinolinic acid in depression, also may play a key role in these
      diseases. Such differences are associated with an imbalance in glutamatergic
      neurotransmission that may contribute to increased levels of NMDA agonism in
      depression and NMDA antagonism in schizophrenia. In addition, immunological
      imbalance results in the increased production of PGE2 in schizophrenia and
      depression, as well as increased COX-2 expression in schizophrenia. Although
      there is evidence supporting the hypothesis that interactions between immune
      system components, IDO, the serotonergic system and glutamatergic
      neurotransmission play a key role in schizophrenia and depression, several gaps
      in knowledge remain, such as regarding the role of genetics, disease course,
      gender and different psychopathological states. There is evidence indicating that
      anti-inflammatory therapy may have beneficial effects in schizophrenia and major
      depression (MD). COX-2 inhibitors have been tested in animal models and in
      preliminary clinical trials, demonstrating favorable activity compared with
      placebo, both in schizophrenia and MD. However, the effects of COX-2 inhibition
      in the CNS, as well as toward different components of the inflammatory system,
      kynurenine metabolism and glutamatergic neurotransmission, require further
      evaluation, which should include clinical trials with larger numbers of patients.
      The potential inflammatory mechanism in schizophrenia and MD, and the possible
      therapeutic advantages of targeting this mechanism in the treatment of these
      disorders is discussed in this review.

PMID- 20047158
TI  - ICE/caspase 1 inhibitors and IL-1beta receptor antagonists as potential
      therapeutics in epilepsy.
AB  - Epilepsy is a disabling neurological disorder that is characterized by recurring,
      unprovoked seizures. Drug-resistant epilepsy affects approximately 30% of
      individuals with epilepsy; thus, one of the main challenges for epilepsy therapy
      is the development of alternative anticonvulsant approaches. The discovery that
      inflammatory mediators contribute significantly to the onset and recurrence of
      seizures in experimental models, as well as the presence of inflammatory
      molecules in human epileptogenic tissue, highlight the possibility of targeting
      specific inflammation-related pathways to control seizures that are otherwise
      resistant to the available anti-epileptic drugs. This review summarizes the proof
      of-principle evidence, obtained in experimental disease models, demonstrating the
      anticonvulsant activity of specific anti-inflammatory drugs, such as inhibitors
      of IL-1-converting enzyme/caspase 1 and antagonists of IL-1beta receptors. Drugs
      that block IL-1beta actions have entered clinical trials as potential
      therapeutics for autoimmune and inflammatory pathologies, and may also have
      therapeutic potential in epilepsies associated with proinflammatory processes in
      the brain.

PMID- 20047159
TI  - FAAH and MAGL inhibitors: therapeutic opportunities from regulating
      endocannabinoid levels.
AB  - Apart from their widespread recreational abuse, the psychoactive preparations of
      the plant Cannabis sativa and its major psychotropic component, Delta9
      tetrahydrocannabinol (THC), are also known for their medicinal properties.
      Following the identification of receptors for THC - the cannabinoid CB1 and CB2
      receptors - in mammals, various pharmaceutical strategies have attempted to
      exploit the properties of the cannabinoid system while minimizing psychotropic
      side effects. The cloning of the cannabinoid CB1 and CB2 receptors enabled the
      discovery of the endogenous agonists of the receptors, the endocannabinoids, and
      eventually led to the identification of enzymes that catalyze endocannabinoid
      inactivation. Unlike exogenously administered THC and synthetic CB1 and CB2
      agonists, the endocannabinoids that are produced endogenously following the onset
      of several pathologies may act in a site- and time-specific manner to minimize
      the consequences of such conditions. This observation has suggested the
      possibility of targeting endocannabinoid-degrading enzymes to prolong the
      precisely regulated pro-homeostatic action of endocannabinoids. Two major enzymes
      have been cloned and investigated thoroughly: fatty acid amide hydrolase (FAAH)
      and monoacylglycerol lipase (MAGL). Inhibitors of these enzymes have demonstrated
      therapeutic benefit in animal models of several disorders, including neuropathic
      pain, anxiety and inflammatory bowel diseases, as well as against the
      proliferation and migration of cancer cells. This review describes the major
      biochemical properties of FAAH and MAGL, and the design and pharmacological
      properties of inhibitors of these enzymes.

PMID- 20047161
TI  - Neurophysiological methodologies: diagnosis of peripheral nerve disease and
      assessment of pharmacological agents.
AB  - Recent developments in the field of neurophysiology have led to the refinement of
      neurophysiological techniques, enabling clinical investigators to assess
      neuropathy patients with greater precision. In addition to conventional nerve
      conduction studies and electromyography, novel axonal excitability techniques and
      quantitative sensory testing may be used to improve diagnosis and to characterize
      and serially monitor peripheral nerve disorders. A significant expansion in the
      number of clinical trials being conducted for neurological indications has
      increased the impetus to further develop neurophysiological measures that reflect
      the responsiveness to drug therapies. Measures such as motor unit number
      estimation and the neurophysiological index may facilitate the advancement of
      compounds in the drug discovery pipeline. This review summarizes several
      electrodiagnostic and neurophysiological techniques, both conventional and novel,
      highlighting recent advances that are relevant to disease diagnosis and the
      assessment of patient response to treatment strategies.

PMID- 20047160
TI  - Neurobiological mechanisms of addiction: focus on corticotropin-releasing factor.
AB  - Drug addiction is a chronically relapsing disorder that is characterized by a
      compulsion to take drugs and loss of control in limiting intake. Medications that
      are on the market for the treatment of drug addiction target either the direct
      reinforcing effects of abuse (eg, naltrexone) or the consequent protracted
      abstinence syndrome (eg, acamprosate). Both conceptual and neurobiological
      advances in research have suggested that brain stress systems contribute to the
      withdrawal/negative affect and preoccupation/anticipation stages of the addiction
      cycle that promote the compulsivity of drug-taking in addiction. Validated animal
      models of the stress component of addiction and improved understanding of the
      neurocircuitry and neuropharmacological mechanisms involved in perturbations of
      this component suggest that corticotropin-releasing factor systems are a viable
      target for the development of future medications for drug addiction.

PMID- 20047162
TI  - Latrepirdine, a potential novel treatment for Alzheimer's disease and
      Huntington's chorea.
AB  - Latrepirdine (Dimebon) is a small-molecule compound under development by
      Medivation Inc and Pfizer Inc for the treatment of Alzheimer's disease and
      Huntington's chorea. Originally developed and marketed as an antihistamine in
      Russia, latrepirdine has since demonstrated potential for the treatment of
      neurodegenerative diseases. Early research suggested that the mechanism of action
      was centered on AChE inhibition and NMDA antagonism. More recent research
      questions these early findings, and other mechanisms of action have been proposed
      and investigated. In phase II clinical trials, latrepirdine demonstrated
      clinically relevant improvements in patients with Alzheimer's disease and
      Huntington's chorea. At the time of publication, phase III clinical trials had
      been initiated. Given the robustness of the phase II clinical data, latrepirdine
      has a high likelihood of success in phase III trials and in subsequently being
      granted regulatory approval.

PMID- 20047163
TI  - BL-1020, an oral antipsychotic agent that reduces dopamine activity and enhances
      GABAA activity, for the treatment of schizophrenia.
AB  - In schizophrenia, a psychiatric disorder that affects approximately 1% of the
      global population and is associated with substantial disability, a significant
      proportion of patients (usually estimated to be at least 30%) fail to respond to
      treatment, and many patients have difficulty continuing treatment because of side
      effects. At the time of publication, all available medications for schizophrenia
      targeted dopamine and other monoamine neurotransmitters. However, a substantial
      amount of research suggests that patients with schizophrenia have underlying
      deficits within the GABA neurotransmitter system. BL-1020, being developed by
      BioLineRx Ltd under license from Tel Aviv University Ltd and Bar-Ilan Research &
      Development Co Ltd, is a novel compound consisting of the well-established
      antipsychotic drug perphenazine and GABA. Preclinical studies of BL-1020
      indicated that the compound penetrated the brain and was efficacious in rodents,
      with a significant reduction in side effects compared with the administration of
      perphenazine. BL-1020 was well tolerated in all clinical trials conducted, and
      clinically meaningful improvements were demonstrated in phase II trials in
      patients with schizophrenia. Further data from phase II and subsequent phase III
      trials will be required to derive conclusions for BL-1020 regarding overall
      efficacy.

PMID- 20047164
TI  - Almorexant, a dual orexin receptor antagonist for the treatment of insomnia.
AB  - Almorexant (ACT-078573) is an orally active dual orexin receptor antagonist that
      is being developed by Actelion Ltd, in collaboration with GlaxoSmithKline plc,
      for the treatment of primary insomnia. Almorexant is a first-in-class compound
      that targets the orexin system, which plays a key role in wake promotion and
      stabilization, in addition to having other regulatory functions. Decreasing
      orexin activity was hypothesized to have a sleep-promoting effect. Preclinical
      studies and phase I clinical trials have demonstrated that almorexant decreases
      alertness and increases sleep in healthy rats, dogs and humans when administered
      during the active phase of the circadian cycle, at peak endogenous orexin tone.
      No significant toxicological or safety concerns have been identified in studies
      in animals and humans, including no evidence of cataplexy, a sudden postural
      muscle tone weakening that is triggered by emotional stimuli and is considered
      unique to narcolepsy. The reported efficacy and safety data for almorexant
      support the continued development of the compound. At the time of publication,
      phase III clinical trials were underway, but no results had been reported;
      Actelion and GlaxoSmithKline were also investigating almorexant for other orexin
      related neurological disorders. The use of an orexin receptor antagonist for the
      treatment of sleep disorders appears to be an approach that may provide unique
      benefits.

PMID- 20047165
TI  - [New occupational diseases in mental health care].

PMID- 20047166
TI  - [Free will in forensic psychiatry].
AB  - BACKGROUND: There is a lack of clarity and some concern about the role that the
      concept of 'free will' plays in the assessment of legal accountability in
      forensic psychiatry. People are particularly concerned that the 'free will'
      concept might embroil psychiatrists in difficult philosophical problems. Recently
      it has been suggested that in order to avoid confusion it would be better if
      forensic psychiatrists ignored the free will concept completely. AIM: To analyse
      the problem of free will in forensic psychiatry and to investigate how psychiatry
      can deal with it. METHOD: Discussions took place about recent forensic
      psychiatric and philosophical literature of free will and legal accountability,
      particularly in the Netherlands. RESULTS: Free will is a serious philosophical
      problem and no solution is yet in sight. Psychiatrists, however, should not let
      themselves be distracted by metaphysical problems. The problem of free will
      points to a significant lack of clarity concerning the nature of the assessment
      of legal accountability itself. The matter needs to be researched and empirical
      ethics seems to be a possible way of approaching the problem. CONCLUSION: The
      problem of free will demonstrates the importance of doing (interdisciplinary)
      research into the assessment of legal accountability, for instance, via empirical
      ethics.

PMID- 20047167
TI  - [Free will not to be neglected in forensic psychiatry].

PMID- 20047168
TI  - [Effectiveness of antidepressants. Implications of two meta-analyses for clinical
      practice].
AB  - BACKGROUND: Following reports of new scientific research there are frequently
      discussions in the media about the effectiveness of antidepressants. AIM: To find
      out whether recently published meta-analyses about the effectiveness of
      antidepressants have consequences for clinical practice. METHOD: Two recent meta
      analyses which investigated the effectiveness of antidepressants are discussed.
      results The two studies were conducted along similar lines using similar methods.
      Both meta-analyses concluded that antidepressants are effective in the more
      serious type of depressive disorders. They are less effective in mild depressive
      disorders. CONCLUSION: On the basis of these two meta-analyses it was concluded
      that antidepressants should be prescribed solely for patients with severe
      depressive disorders.

PMID- 20047169
TI  - [Disclosure of conflicts of interest in the Tijdschrift voor Psychiatrie].
AB  - Between March 2000 and December 2008 authors disclosed conflicts of interest in
      9% of articles in the Tijdschrift voor Psychiatrie. For the same period, in the
      articles dealing with pharmaceuticals, the percentage of articles containing
      disclosures of conflict of interest was considerably higher, namely 24%. The
      policy of the journal with regard to the disclosure of conflicts of interest has
      helped to promote transparency. Further efforts are needed to encourage authors
      to disclose conflicts of interest.

PMID- 20047170
TI  - [Reaction on 'Less need for insulin, a surprising effect of phototherapy in
      insulin-dependent diabetes mellitus'].

PMID- 20047171
TI  - [New concepts for practice guideline development in German child and adolescent
      psychiatry and psychotherapy].

PMID- 20047172
TI  - [Algorithms for the medical treatment of Attention-Deficit/Hyperactivity Disorder
      with specific co-morbidities].
AB  - BACKGROUND: In clinical practice Attention Deficit Hyperactivity Disorder (ADHD)
      is a challenge for diagnostic and therapeutic effort due to a number of co
      morbidities, e.g., depression, anxiety disorders, Tourette Syndrome and impulsive
      aggression that can be a complication or a result of the core symptoms or evolve
      parallel to the basic disorder. The therapeutic strategies incorporate a
      multimodal access with a combination of psychosocial, psychotherapeutic and
      medical measures. The combination of various medical substances for an effective
      treatment of these co-morbidities, especially Serotonin-Reuptake Inhibitors
      (SSRIs) and atypical neuroleptics with psychostimulants has substantially reduced
      the occurrence of the main symptoms of the disorder in many cases and thus can
      also lead to a decrease in the occurrence of co-morbidities. Where this strategy
      fails to suffice, it is recommended to consider medical treatment strategies in
      combination with other substances that alternatively or in combination with
      psychostimulants increasingly positively influence co-morbid symptoms. OBJECTIVE
      AND METHOD: Based on a Medline literature search we report the results of
      combined medical approaches for an effective medical treatment of the ADHD core
      symptoms accompanied by serious co-morbid symptoms. Hereby we focused on the
      above cited disorders. Combined treatment options that include psychostimulants
      are considered in particular. Moreover, recommendations for medical treatment
      strategies oriented to the clinical cardinal symptoms are presented in the form
      of algorithms. Evidence-based literature and practical experience are critically
      reviewed. RESULTS: In most cases it will be sufficient to begin the treatment
      with a psychostimulant because co-morbid symptoms also will be significantly
      reduced. However, if the latter are in the foreground of the clinical picture,
      antidepressants or neuroleptics are to be considered as primary or equivalent
      treatment options. CONCLUSIONS: Since in Germany most of the substances discussed
      are not licensed for use in paediatric treatment, proofs of efficacy in children
      are lacking. One also must reckon with the frequent occurrence of side effects.
      Finally, little data exist on treatments that include the use of
      psychostimulants.

PMID- 20047173
TI  - [Undetected Hashimoto encephalopathy--a diagnostic challenge in child psychiatry
      and child neurology].
AB  - The literature is reviewed. Hashimoto encephalopathy is a steroid-responsive
      encephalopathy associated with Hashimoto thyroiditis (SREHT). The incidence of
      SREHT in childhood is underestimated. Two subtypes have been described. The
      diffuse progressive type is associated with insidious onset and progressive
      impairment of mental status, such as confusion, somnolence, and psychosis. The
      vasculitic type is characterized by acute stroke-like episodes associated with
      focal neurologic features and seizures. Hashimoto encephalopathy (SREHT) is a
      clinical condition with elevated thyroid antibody titers encompassing persistent
      or relapsing seizures, myoclonus, focal neurologic deficits and neuropsychiatric
      disorders such as psychosis, delusions and hallucinations, and affective
      disorders. By far, the vast majority of reports on paediatric and adult patients
      describe a dramatic clinical response to either methylprednisolone pulse therapy
      or daily oral prednisone or prednisolone.

PMID- 20047174
TI  - [Outpatient treatment of selective mutism: long-standing selective mutism in a 17
      year-old male].
AB  - The present case report describes the successful treatment of a 17 year old male
      adolescent suffering for 10 years from selective mutism. Following a summary
      review of recent publications on therapy approaches, the report describes the
      treatment concept in the present case, including detailed assessment of co-morbid
      disorders, motivation for change, behaviour therapy with supporting drug
      intervention, and intensive co-operation with parents and other caretakers.

PMID- 20047175
TI  - [Psychopharmacotherapy in adolescents with borderline personality disorder in
      inpatient and outpatient psychiatric treatment].
AB  - OBJECTIVE: The majority of adult patients with borderline personality disorder
      (BPD) are treated with psychotropic drugs. However, there are no data on
      psychotropic therapy in adolescents. This study examines the prevalence of BPD in
      an adolescent population undergoing either inpatient or outpatient psychiatric
      treatment and assesses psychotropic prescription patterns in adolescent in- and
      outpatients with BPD. METHODS: Out of a population of adolescents undergoing
      psychiatric treatment over a seven-year observation period, 58 adolescent
      patients with BPD (16.7 +/- 2.5 years) were investigated retrospectively with
      regard to their first episode of treatment, type of medication, and different
      risk variables. RESULTS: Out of the investigated population, 37 inpatients and 21
      outpatients received treatment. Inpatients were shown to have higher rates of
      risk variables (approx. 68% with co-morbid disorders and approx. 49% with self
      harmful behaviour, significantly (p < .001) more attempted suicides in their
      patient history) and higher rates of psychotropic treatment (p < .001).
      Antidepressants (SSRI and NaSSA) were most commonly prescribed, followed by
      neuroleptics. More than 50% of the medicated patients were treated with multiple
      psychotropic drugs administered simultaneously. CONCLUSIONS: Pharmacotherapy in
      BPD has a high and increasing therapeutic value, with the prescription of
      psychotropic drugs being primarily symptom-orientated. Pharmacotherapy of co
      morbid disorders should be accorded equal treatment priority. In line with this,
      psychotropic treatment of BPD in adolescents is increasingly important. Inpatient
      adolescents are more burdened in terms of psychiatric risk variables, and also
      receive medication more often.

PMID- 20047176
TI  - [Subjective evaluation of DBT treatment by adolescent patients with eating
      disorders and the correlation with evaluations by their parents and
      psychotherapists].
AB  - OBJECTIVE: The subjective evaluation of a psychotherapeutic treatment may be an
      essential aspect of the recovery from an eating disorder. Our study investigates
      the subjective treatment evaluation by patients with eating disorders and the
      accordance with their parents' and psychotherapist's evaluation. METHOD: In a
      sample of 41 eating-disorder patients (M(Age) = 16.3; SD = 1.26), their parents
      and psychotherapists, we used a questionnaire (FBB) to assess satisfaction with
      Dialectical Behavioral Therapy treatment. RESULTS: Our results show good ratings,
      as well as good correlations between patients and parents. CONCLUSIONS: The
      findings implicate the importance of assessing a subjective therapy rating in
      addition to objective parameters.

PMID- 20047180
TI  - Does the fixed combination of bimatoprost/timolol really produce a better
      benefit/risk balance than the fixed combination of latanoprost/timolol?

PMID- 20047183
TI  - Sutureless amniotic membrane fixation with fibrin glue in symptomatic bullous
      keratopathy with poor visual potential.

PMID- 20047184
TI  - The effect of different doses of intracameral bevacizumab on surgical outcomes of
      trabeculectomy for neovascular glaucoma.

PMID- 20047187
TI  - Generation of a triple-gene knockout mammalian cell line using engineered zinc
      finger nucleases.
AB  - Mammalian cells with multi-gene knockouts could be of considerable utility in
      research, drug discovery, and cell-based therapeutics. However, existing methods
      for targeted gene deletion require sequential rounds of homologous recombination
      and drug selection to isolate rare desired events--a process sufficiently
      laborious to limit application to individual loci. Here we present a solution to
      this problem. Firstly, we report the development of zinc-finger nucleases (ZFNs)
      targeted to cleave three independent genes with known null phenotypes. Mammalian
      cells exposed to each ZFN pair in turn resulted in the generation of cell lines
      harboring single, double, and triple gene knockouts, that is, the successful
      disruption of two, four, and six alleles. All three biallelic knockout events
      were obtained at frequencies of >1% without the use of selection, displayed the
      expected knockout phenotype(s), and harbored DNA mutations centered at the ZFN
      binding sites. These data demonstrate the utility of ZFNs in multi-locus genome
      engineering.

PMID- 20047188
TI  - Disulfide trapping of protein complexes on the yeast surface.
AB  - Protein complexes are common in nature and play important roles in biology, but
      studying the quaternary structure formation in vitro is challenging since it
      involves lengthy and expensive biochemical steps. There are frequent technical
      difficulties as well with the sensitivity and resolution of the assays. In this
      regard, a technique that can analyze protein-protein interactions in high
      throughput would be a useful experimental tool. Here, we introduce a combination
      of yeast display and disulfide trapping that we refer to as stabilization of
      transient and unstable complexes by engineered disulfide (STUCKED) that can be
      used to detect the formation of a broad spectrum of protein complexes on the
      yeast surface using fluorescence labeling. The technique uses an engineered
      intersubunit disulfide to covalently crosslink the subunits of a complex, so that
      the disulfide-trapped complex can be displayed on the yeast surface for detection
      and analysis. Transient protein complexes are difficult to display on the yeast
      surface, since they may dissociate before they can be detected due to a long
      induction period in yeast. To this end, we show that three different quaternary
      structures with the subunit dissociation constant K(d) approximately 0.5-20
      microM, the antibody variable domain (Fv), the IL-8 dimer, and the p53-MDM2
      complex, cannot be displayed on the yeast surface as a noncovalent complex.
      However, when we introduce an interchain disulfide between the subunits, all
      three systems are efficiently displayed on the yeast surface, showing that
      disulfide trapping can help display protein complexes that cannot be displayed
      otherwise. We also demonstrate that a disulfide forms only between the subunits
      that interact specifically, the displayed complexes exhibit functional
      characteristics that are expected of wt proteins, the mutations that decrease the
      affinity of subunit interaction also reduce the display efficiency, and most of
      the disulfide stabilized complexes are formed within the secretory pathway during
      export to the surface. Disulfide crosslinking is therefore a convenient way to
      study weak protein association in the context of yeast display.

PMID- 20047189
TI  - High-level rapid production of full-size monoclonal antibodies in plants by a
      single-vector DNA replicon system.
AB  - Plant viral vectors have great potential in rapid production of important
      pharmaceutical proteins. However, high-yield production of hetero-oligomeric
      proteins that require the expression and assembly of two or more protein subunits
      often suffers problems due to the "competing" nature of viral vectors derived
      from the same virus. Previously we reported that a bean yellow dwarf virus
      (BeYDV)-derived, three-component DNA replicon system allows rapid production of
      single recombinant proteins in plants (Huang et al., 2009. Biotechnol Bioeng 103:
      706-714). In this article, we report further development of this expression
      system for its application in high-yield production of oligomeric protein
      complexes including monoclonal antibodies (mAbs) in plants. We showed that the
      BeYDV replicon system permits simultaneous efficient replication of two DNA
      replicons and thus, high-level accumulation of two recombinant proteins in the
      same plant cell. We also demonstrated that a single vector that contains multiple
      replicon cassettes was as efficient as the three-component system in driving the
      expression of two distinct proteins. Using either the non-competing, three-vector
      system or the multi-replicon single vector, we produced both the heavy and light
      chain subunits of a protective IgG mAb 6D8 against Ebola virus GP1 (Wilson et
      al., 2000. Science 287: 1664-1666) at 0.5 mg of mAb per gram leaf fresh weight
      within 4 days post-infiltration of Nicotiana benthamiana leaves. We further
      demonstrated that full-size tetrameric IgG complex containing two heavy and two
      light chains was efficiently assembled and readily purified, and retained its
      functionality in specific binding to inactivated Ebola virus. Thus, our single
      vector replicon system provides high-yield production capacity for hetero
      oligomeric proteins, yet eliminates the difficult task of identifying non
      competing virus and the need for co-infection of multiple expression modules. The
      multi-replicon vector represents a significant advance in transient expression
      technology for antibody production in plants.

PMID- 20047190
TI  - Covalent dimerization of camelidae anti-human TNF-alpha single domain antibodies
      by the constant kappa light chain domain improves neutralizing activity.
AB  - The tumor necrosis factor-alpha (TNFalpha) plays an important role in a number of
      chronic inflammatory disorders. Monoclonal camelidae variable heavy chain domain
      only antibodies (V(H)H) have been developed to antagonize the action of human
      TNFalpha (anti-TNF-V(H)H). Here we describe a strategy to obtain functional
      dimeric anti-TNF-V(H)H molecules, based on the C-terminal fusion of a kappa light
      chain domain to the anti-TNF-V(H)H. The resulting fusion protein was transiently
      expressed by use of viral vectors in Nicotiana benthamiana((Nb)) leaves and
      purified. Competitive ELISA and cell cytotoxicity assays revealed that the
      dimerized anti-(Nb)TNF-V(H)H(Ckappa) proteins blocked TNFalpha-activity more
      effectively than either the monomeric Escherichia coli((Ec)) produced anti
      (Ec)TNF-V(H)H or the monomeric anti-(Nb)TNF-V(H)H(Ckappa). We suggest that
      enhanced inhibition shown by dimeric anti-(Nb)TNF-V(H)H(Ckappa) proteins is
      achieved by an increase in avidity.

PMID- 20047191
TI  - Dissolved oxygen and pH profile evolution after cryovial thaw and repeated cell
      passaging in a T-75 flask.
AB  - Routine cell culture is done in small-scale disposable vessels (typically 0.1-100
      mL volumes) in academia and industry. Despite their wide use in bioprocess
      development (i.e., process optimization and process validation), miniature
      process scouting devices (PSDs) are considered "black boxes" because they are
      generally not equipped with sensors. In this study, we show that on-line
      monitoring of dissolved oxygen (DO) and pH in a T-75 flask-based PSD can be
      achieved during cell passaging and that this information can be linked to
      different cellular metabolic states. In this case, on-line monitoring of DO and
      pH show three distinctive metabolic regions in passages 1-18, 19-28, 29-54 and in
      particular, the shift in the pH curve, the specific oxygen uptake rate (q(O2)),
      and the lactate production rate to the oxygen consumption rate yield (Y(Lac/ox))
      confirm the existence of these distinctive metabolic regions. These findings are
      particularly useful because they show that sensor equipped PSDs can help to
      monitor cell culture behavior after thaw, in pre- and seed culture prior to scale
      up and in development/optimization studies. Such routine monitoring will help to
      develop more consistent cell culture techniques.

PMID- 20047192
TI  - Influence of the hydrostatic pressure and pH on the asymmetric 2-hydroxyketone
      formation catalyzed by Pseudomonas putida benzoylformate decarboxylase and
      variants thereof.
AB  - Benzoylformate decarboxylase (BFD) from Pseudomonas putida is a thiamine
      diphosphate-dependent (ThDP) enzyme that catalyzes the asymmetric C--C bond
      formation to (S)-2-hydroxypropiophenone [(S)-HPP] starting from benzaldehyde and
      acetaldehyde. The enantioselectivity of BFD was shown to be a function of
      temperature and substrate concentration. It can additionally be changed by site
      directed mutagenesis on hot spot positions in the active site. In this article,
      we present the effect of hydrostatic pressure up to 250 MPa on the
      enantioselectivity for the recombinant wtBFD as well as for the variants BFD
      F464I, BFD A460I, and BFD A460I-F464I. A general tendency toward lower amounts of
      (S)-HPP could be observed at increasing pressures. For two of these variants an
      increase in pressure even caused an inversion in the enantioselectivity and thus
      increasing enantiomeric excesses, respectively. A pressure-induced increase in
      enantioselectivity could therefore be observed for the first time in biocatalysis
      to the best of our knowledge. Furthermore, the pH is shown to be a parameter that
      also significantly influences the enantioselectivity of the reaction mentioned
      above.

PMID- 20047194
TI  - Cyclic acetal hydroxyapatite composites and endogenous osteogenic gene expression
      of rat marrow stromal cells.
AB  - In this study, bone marrow stromal cells (BMSCs) were differentiated on cyclic
      acetal composites containing hydroxyapatite (HA) particles (110 or 550 nm). These
      composites were evaluated for their role in influencing osteogenic signalling by
      encapsulated BMSCs. While a number of factors exert influence on osteogenic
      signalling during the production of an osteogenic matrix, we hypothesize that HA
      particles may upregulate bone growth factor expression due to enhanced BMSC
      adhesion. To this end, fluorescence-activated cell sorting (FACS) analysis was
      performed for the evaluation of BMSC surface marker expression after culture on
      two-dimensional (2D) cyclic acetal/HA composites. Three-dimensional (3D)
      composites were then fabricated by incorporating 110 or 550 nm HA particles at 5,
      10 and 50 ng/ml concentrations. Bone growth factor molecules (TGFbeta1, FGF-2 and
      PDGFa), bone biomarker molecules (ALP, OC, OPN and OCN) and extracellular matrix
      related molecules (FN, MMP-13, Dmp1 and aggrecan) were selected for evaluation of
      osteogenic signalling mechanisms when in presence of these composites. FACS
      results at day 0 demonstrated that BMSCs were a heterogeneous population with a
      small percentage of cells staining positive for CD29, CD90 and CD51/61, while
      staining negative for CD34 and CD45. At day 3, a significant enrichment of cells
      staining strongly for CD29, CD90 and CD51/61 was achieved. Gene expression
      patterns for bone growth factors and extracellular matrix molecules were found to
      be largely dependent upon the size of HA particles. Bone marker molecules, except
      OCN, had unaltered expression patterns in response to the varied size of HA
      particles. Overall, the results indicate that larger-sized HA particles
      upregulate PDGF and these groups were also associated with the most significant
      increase in osteodifferentiation markers, particularly ALP. Our results suggest
      that endogenous signalling is dependent upon material properties. Furthermore, we
      propose that studying gene expression patterns induced by the surrounding
      biomaterials environment is a fundamental step in the creation of engineered
      tissues.

PMID- 20047195
TI  - Set-up and docking of the da Vinci surgical system: prospective analysis of
      initial experience.
AB  - BACKGROUND: Set-up and docking of the da Vinci surgical system are assumed to
      extend overall operating times. We hypothesized that these tasks could be
      achieved in adequate times. Therefore, a prospective analysis of set-up and
      docking times of the da Vinci Surgical System was conducted. METHODS: We
      prospectively analysed set-up and docking times with the da Vinci surgical system
      in our division. RESULTS: Ninety-six patients were operated on over 30 months in
      our institution. Median set-up time was 22 (range 9-50) min and median docking
      time was 10 (range 2-70) min. Surgeons with previous docking experience were
      significantly faster than inexperienced surgeons: 8 (range 2-50) vs. 17.5 (range
      10-70) min. Both set-up and docking showed a fast learning curve. CONCLUSION: The
      data support the conclusion that both set-up and docking of the robot can be
      achieved in adequate times and have a low impact on overall operating time.

PMID- 20047196
TI  - Ultrasonographic prediction of homozygous alpha0-thalassemia using placental
      thickness, fetal cardiothoracic ratio and middle cerebral artery Doppler: alone
      or in combination?
AB  - OBJECTIVE: To compare the predictive values of three ultrasonographic parameters:
      placental thickness (PT), fetal cardiothoracic ratio (CTR) and middle cerebral
      artery peak systolic velocity (MCA-PSV), alone or in combination, in pregnancies
      affected by homozygous alpha(0)-thalassemia at 12-20 weeks' gestation. METHODS:
      Pregnant women at risk of carrying a fetus affected by homozygous alpha(0)
      thalassemia were studied from 1995 to 2006 using serial ultrasonography at 12-15
      weeks, 16-20 weeks and 30 weeks' gestation. We measured CTR and PT from 1995, and
      MCA-PSV as well from 1997. An invasive prenatal test was offered if cardiomegaly
      with or without placentomegaly was detected but the MCA-PSV results were used
      only retrospectively for analysis. RESULTS: Of a total of 777 at-risk fetuses
      studied, 138 (17.8%) were affected by homozygous alpha(0)-thalassemia. At 12-15
      weeks' gestation, 598 ultrasound examinations were performed. CTR was better than
      both PT and MCA-PSV in the prediction of affected pregnancies. The highest
      sensitivity (98.3%) was achieved by the combination of CTR and/or MCA-PSV at a
      false-positive rate of 15.8%. At 16-20 weeks' gestation, 410 ultrasound
      examinations were performed, 121 of which were at the patient's first visit and
      289 of which were at a follow-up visit. Both CTR and MCA-PSV predicted the
      affected pregnancies equally well. The sensitivity of CTR was 100.0%, but the
      false-positive rate was 5.2%. In contrast, the false-positive rate of MCA-PSV
      alone was 1.4% and that of the combination of CTR and MCA-PSV was 0%, although
      their sensitivities were less than 65%. CONCLUSIONS: The data suggest that adding
      MCA-PSV to CTR in the prediction of homozygous alpha(0)-thalassemia can increase
      the sensitivity at 12-15 weeks and decrease the false-positive rate at 16-20
      weeks' gestation.

PMID- 20047197
TI  - Regulation of high-density lipoprotein by inflammatory cytokines: establishing
      links between immune dysfunction and cardiovascular disease.
AB  - Coronary artery disease is a primary co-morbidity in metabolic diseases such as
      metabolic syndrome, diabetes and obesity. One contributing risk factor for
      coronary artery disease is low high-density lipoprotein-cholesterol (HDLc).
      Several factors influence steady-state HDLc levels, including diet, genetics and
      environment. Perhaps more important to coronary artery disease is factors that
      attribute to the dynamics of reverse cholesterol transport, storage, and
      excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to
      serve as a cholesterol acceptor and transporter all contribute to HDLc's function
      as a negative regulator of cardiovascular disease. With the recent failure of
      torcetrapid, focus is being placed on HDLc biology and its role in various
      metabolic diseases. Low HDLc levels are often associated with an increased state
      of background inflammation. Recently, several syndromes with clear pro
      inflammatory components have been shown to be inversely correlated with low HDLc
      levels in the absence of obesity, diabetes and metabolic syndrome. Early studies
      with HDLc during the acute-phase response suggest that HDLc is substantially
      physically modified during acute infection and sepsis, and recent studies show
      that HDLc is physically modified by chronic pro-inflammatory disease. In this
      review, several of these connections are described and cytokine signalling
      related to HDLc is examined.

PMID- 20047198
TI  - Annual report of the Australian Meningococcal Surveillance Programme, 2008.
AB  - In 2008, there were 260 laboratory-confirmed cases of invasive meningococcal
      disease (IMD) analysed by the National Neisseria Network, a nationwide network of
      reference laboratories. One hundred and forty-nine isolates of Neisseria
      meningitidis from invasive cases of meningococcal disease were available for
      which the phenotypes (serogroup, serotype and serosubtype) and antibiotic
      susceptibility were determined. An additional 111 cases were confirmed by non
      culture based methods. Nationally, 223 (85%) laboratory-confirmed cases where a
      serogroup was determined were infected with serogroup B and 17 (6.5%) infected
      with serogroup C meningococci. Nationally, the total number of confirmed cases
      has remained relatively stable since 2006, but the number of cases in each
      jurisdiction may vary from year to year. Queensland had the highest number of
      recorded cases in 2008. Typical primary and secondary disease peaks were observed
      in those aged 4 years or less and in adolescents and young adults respectively.
      Serogroup B cases predominated in all age groups and jurisdictions. The common
      phenotypes circulating in Australia were again B:15:P1.7 and B:4:P1.4. Although
      serogroup C cases were numerically low, phenotype C:2a:P1.5 predominated in this
      group. No evidence of meningococcal capsular 'switching' was detected. About
      three-quarters of all isolates showed decreased susceptibility to the penicillin
      group of antibiotics (MIC 0.06-0.5 mg/L). All isolates remained susceptible to
      ceftriaxone. One isolate had reduced susceptibility to rifampicin and two to
      ciprofloxacin.

PMID- 20047199
TI  - Annual report of the Australian Gonococcal Surveillance Programme, 2008.
AB  - The Australian Gonococcal Surveillance Programme monitors the antibiotic
      susceptibility of Neisseria gonorrhoeae isolated in all states and territories.
      In 2008 the in vitro susceptibility of 3,110 isolates of gonococci from public
      and private sector sources was determined by standardised methods. Different
      antibiotic susceptibility patterns were again seen in the various jurisdictions
      and regions. Resistance to the penicillins nationally was at 44% and ranged
      between 25% in Queensland and 73% in South Australia with the exception of the
      Northern Territory, where the proportion of drug resistant strains was 4%.
      Quinolone resistance in gonococci isolates also continued to increase so that
      nationally 54% of all isolates were ciprofloxacin-resistant, and most of this
      resistance was at high minimal inhibitory concentrations (MIC) levels. The
      proportions of quinolone resistant gonococci detected ranged between 80% in South
      Australia and 31% in Western Australia. All isolates remained sensitive to
      spectinomycin. Approximately 1.1% of isolates showed some decreased
      susceptibility to ceftriaxone (MIC 0.06 mg/L or more) and azithromycin resistance
      was also present in low numbers of gonococci with MICs up to 16 mg/L. A high
      proportion of gonococci examined in larger urban centres were from male patients
      and rectal and pharyngeal isolates were common in men. In other centres and in
      rural Australia the male to female ratio of cases was lower, and most isolates
      were from the genital tract.

PMID- 20047200
TI  - OzFoodNet quarterly report, 1 April to 30 June 2009.

PMID- 20047201
TI  - Gene analysis and biomarker identification.

PMID- 20047202
TI  - Unexpected presence of mycoplasma probes on human microarrays.

PMID- 20047203
TI  - An Urgent Matter. Identifying Your Patients' Cardiovascular Risk and Improving
      Their Outcomes. Introduction.

PMID- 20047204
TI  - Medical archives and MSS news, 2009.

PMID- 20047206
TI  - [Implants in partially edentulous patients with history of periodontal disease].
AB  - BACKGROUND: Microbiota associated with periodontal diseases were also associated
      with periimplant diseases. The purpose of this study was to determine the
      clinical status and composition of subgingival microbiota of implants and natural
      teeth in a group of partially edentulous patients with history of periodontal
      disease. METHODS: 38 partially edentulous patients with history of periodontal
      disease, treated with dental implants, were selected for this study. Patients
      selected for the study were in good health condition and did not take any
      antibiotics in the last six months. One year after second stage surgery a total
      of 72 implants and 38 teeth underwent clinical and microbiological examination.
      Clinical parameters were PD, PAL, PI and GI. Subgingival plaque samples were
      analyzed by dark-field microscopy and cultural analysis. RESULTS: Clinical
      parameters didn't show any significant differences between periodontal and
      periimplant tissues. Dark-field microscopic examination showed higher prevalence
      of rods and spirochetes around implants than around teeth. There were no
      differences detected by cultural examination in the subgingival microbiota at
      peri-implant and periodontal sites. CONCLUSIONS: Findings from this study showed
      no differences between implants and teeth in partially edentulous patients with
      history of periodontal disease one year after second stage surgery. Implants were
      colonized by microbiota similar to that observed around teeth and were well
      maintained in patients with a history of periodontitis.

PMID- 20047205
TI  - Biocompatibility in vitro of titanium dental implants. Immunocytochemical
      expression of fibronectin and extracellular matrix receptors.
AB  - BACKGROUND: Cell-substratum interactions play a peculiar role in cell
      proliferation, differentiation and migration. They are regulated by various
      glycoproteins, among which fibronectin, and by receptors connecting cells to the
      extracellular matrix, i.e. integrins. Therefore, the aim of this study was to
      correlate the proliferation rates of the human fibroblast line WI-38 cultured in
      presence of titanium dental implants to cell adhesion capability to substrata.
      METHODS: WI-38 fibroblasts were cultured in presence of four dental implants in
      titanium (one hydroxyapatite coated) for 48, 72 and 96 hours. Cell proliferation
      was evaluated by detecting 5-bromodeoxyuridine incorporation. Fibronectin
      organization and alpha5beta1 integrin expression were evidenced by indirect
      immunofluorescence. RESULTS: A correlation between fibronectin organization and
      cell proliferation rates was demonstrated: cultures showing fibronectin mainly
      organized in fibrils presented the highest cell proliferation degrees. After 96
      hours, the observed decrease of the number of proliferating cells corresponded to
      a different fibronectin organization. In presence of the hydroxyapatite coated
      implant, colocalization of fibronectin and alpha5beta1 integrin was represented
      in focal contacts in cultures exhibiting the highest proliferation rate, while
      cells with the lowest proliferation one expressed alpha5beta1 integrin in point
      contacts. CONCLUSIONS: Evidences obtained in this work showed that both the
      organization of fibronectin and the expression of alpha5beta1 integrin are
      strictly correlated to cell proliferation rates. Therefore, these parameters
      could be useful for evaluating the biocompatibility of dental materials in vitro.

PMID- 20047207
TI  - [Thermoelastic analysis of nickel-titanium endodontic files].
AB  - BACKGROUND: Technological progress in the endodontic field has allowed the
      creation of innovative nickel-titanium endodontic instruments, made with a
      superelastic alloy with a reduced modulus of elasticity. The elastic properties
      of the NiTi alloy can undergo significant variations in connection with
      mechanical movements and cyclic fatigue induced on the instruments caused by
      their repeated usage, especially in canals which are anatomically difficult to
      shape. The state of tension of the instrument determines a deformation of the
      geometry of the files and, therefore, a modification in their properties.
      Similarly to mechanical stress, thermal treatments can influence the properties
      of the alloy. The aim of the study is to subject the NiTi alloy to repeated
      thermomechanical cycles, examining the influence of the mechanical and thermal
      stress on the temperature at the beginning and end of the martensite
      transformation, on the increase of recovery of deformation during the cooling
      phase and on the change in the internal structure of the material. METHODS: The
      instruments (30 ProFile Maillefer) were subdivided into 5 groups: Group I,
      composed of 6 new ProFiles submitted to 14 sterilization cycles in an autoclave
      for 30 minutes each; Group II, formed by 6 unused ProFiles subjected to one
      sterilization cycle in an autoclave; Group III made up of 6 new ProFiles used as
      controls; Group IV made up of 6 ProFiles submitted to clinical use on endodontic
      simulators in plexiglas for a total time of 240 seconds; Group V consisting of 6
      ProFiles used on endodontic simulators for a total time of 480 seconds. All the
      above mentioned samples were tested using a thermomechanic dynamic analyzer
      (DMTA) produced by Rheometric Scientific. RESULTS: The files from Group III
      (control) show an elastic deformation curve typical of nickel-titanium
      instruments. The samples from Groups IV and V subjected to sequential use on
      endodontic simulators evidenced modifications in their elastic behaviour compared
      to the control instruments. The operative use caused modifications in the
      original properties of the alloy, with a reduction in elasticity proportional to
      the number of uses. The instruments that underwent 14 cycles of sterilization in
      the autoclave (I group) present dynamic analysis curves which are different
      compared to the new unsterilized ProFiles. After 14 cycles there is a
      modification in the response of the instruments to thermodynamic stress.
      CONCLUSIONS: Both the samples undergoing repeated mechanical stress on Plexiglas
      endodontic simulators and those sterilized in the autoclave at thermodynamic
      analysis show significant modification in modulus of elasti- city. The different
      taper does not influence the experimental results, there not being any
      significant differences found in the elastic behaviour between ProFiles.

PMID- 20047208
TI  - [Release of nickel from orthodontic appliances].
AB  - BACKGROUND: The increase of orthodontic treatments in the last few years has
      drawn the attention of operators on the possible side effects connected with the
      application of fixed orthodontic appliances. These effects include allergic
      reactions and cytotoxic phenomena caused by orthodontic materials on tissues of
      the oral cavity. The introduction of high nickel content materials has received
      considerable attention for the high incidence of nickel sensitization. Cases of
      patients who developed hypersensitivity reaction after the application of
      orthodontic appliances are reported in the literature. These allergic reactions
      are the consequence of the electrochemical breakdown which the metallic alloys
      undergo in oral fluids. METHODS: Therefore this study evaluates the quantity of
      nickel ions released from the orthodontic appliances in aqueous solutions at
      different pH during a period of 28 days. The solutions have been analyzed by
      atomic absorption spectrophotometry. RESULTS: The results indicate that the
      quantities of nickel released are higher in the solutions with a lower pH and in
      the first days of the experiment. The cumulative values obtained after 28 days in
      the solutions at lower pH can be considered negligible compared to nickel
      dietetic daily intake. CONCLUSIONS: Therefore the results are reassuring to the
      application of orthodontic appliances, but do not exclude that little quantities
      of nickel may cause a state of sensitization and allergic reaction on sensitized
      patients.

PMID- 20047209
TI  - [Glutathione-S-transferase expression in oral squamous cell carcinoma].
AB  - BACKGROUND: A large number of oral cancer patients shows poor or partial response
      to chemotherapy and the mechanisms are poorly understood. Glutathione-S
      transferase (GST) is one of the molecules involved in resistance to natural
      product-based chemotherapeutics. It is an enzyme able to conjugate several
      substances (metabolites, drugs) to reduct glutathione. Today several isoenzymes
      of GST are known: GST-alpha, GST-mu, GST-pi, GST-theta. Over-expression of
      glutathione S-transferase-pi class isozyme is often associated with malignant
      transformation. Several studies reported that GST-pi staining patterns and their
      distribution may be helpful in identifying high-risk oral lesions. However, GST
      is surely involved in resistance to alchilant agents. OBJECTIVE: To verify the
      possibility of implication of GST in oral cancerogenesis and in natural
      chemioresistance, the authors examined the protein expression patterns by
      immunohistochemistry in paraffin-embedded specimens of primary untreated oral
      cancers (OSCC). METHODS: GST-a and GST-pi expression in 17 cases of OSCC at
      different degree of cellular differentiation have been evaluated by
      immunohistochemistry. RESULTS: The GST-pi expression in primary tumours
      predominantly varied from mild to moderate levels. The GST-a expression was often
      quite similar to GST-pi expression with a few exceptions. CONCLUSIONS: Expression
      of GST enzymes is an important signal for multidrug resistance: positive staining
      for both GST-pi and GST-a could constitute a hallmark of chemoresistant groups of
      OSSC.

PMID- 20047210
TI  - [Odontostomatologic symptomatology in eating disorders. A controlled study].
AB  - BACKGROUND: This study investigated odontostomatologic signs and symptoms
      associated with Anorexia Nervosa and Bulimia Nervosa (Eating Disorders, ED).
      METHODS: The authors have examined the following conditions in a group of 14
      female subjects (average age: 23.5 +/-4.8) suffering for ED, compared to a
      control group of 12 female subjects (average age: 22.58 +/-1.83) negative for ED
      diagnostic criteria: temporo-mandibular joint status, salivary pH, periodontal
      indexes (plaque index, bleeding index, pockets presence, gingival recession
      presence), dental indexes (DMF-T, DMF-S; dental erosion or perymolisis), salivary
      glands swelling, oral hygiene habits (related to vomiting behavior). RESULTS: The
      results obtained revealed a greater prevalence of gingival recession, diffuse
      marginal gingivitis, perymolysis, salivary glands involvement, lower salivary pH
      in the Eating Disorders (ED) group when compared with a non-ED control group. The
      results, obtained for the first time from a group of Italian subjects resident in
      a mediterranean country, agree with those obtained by authors working in an anglo
      saxon area. CONCLUSIONS: Since odontostomatologic pathologies may be the only
      detectable sign of Anorexia Nervosa and/or Bulimia Nervosa,the data presented in
      this study could facilitate the early identification of these patients and
      provide guidelines for the evaluation of oral pathologies in anorexic and bulimic
      patients.

PMID- 20047211
TI  - [The use of Bichat's fat pad in temporomandibular joint surgery. First
      evaluation].
AB  - BACKGROUND: The study aimed to evaluate the possibility of using Bichat's fit pad
      as a free graft in the surgical treatment of ankylosis of the temporomandibular
      joint. METHODS: A retrospective study with a follow-up from 9 to 12 months was
      performed in six patients with ankylosis of the temporomandibular joint, for a
      total of nine joints treated at the Maxillofacial Surgical Unit of George Eastman
      Hospital in Rome. Five joints were treated using Bichat's fat pad and four with a
      myofacial flap of temporal muscle. Surgery was performed under general
      anesthesia. The ankylotic block was removed through a preauricular access and a
      graft was then inserted between the operated bone surfaces. All patients
      underwent a complete clinical examination to record maximum jaw aperture, lateral
      movements and protrusion. The following X-rays were also performed: tooth arches,
      bilateral temporomandibular stratigraphy in PA and LL projections,; with mouth
      open and closed, and CT using an axial and coronal projection. RESULTS: The tests
      showed good functional recovery of the joint after arthrotomy and free pad graft.
      No patient showed lateral deviation in maximum aperture or postoperative
      malocclusion. CONCLUSIONS: The technique used was simple and represents a valid
      alternative to other solutions. It is mainly indicated in the event of
      coronoidectomy concomitant to the removal of ankylosis or if the temporal muscle
      is not available.

PMID- 20047212
TI  - [Effects of calcium way of Schwann cells on damage of peripheral nerve induced by
      acrylamide].
AB  - OBJECTIVE: To explore the mechanism of Schwann cells on damage of peripheral
      nerve injured by acrylamide. METHODS: (1) Animal model: the neurobehavior and
      pathologic changes within exposure and recovery period were observed. The changes
      of Synapsin-I and S-100beta were measured by immunohistochemical method. (2) Cell
      mode: in this study, primary culture of Schwann cells and dorsal root ganglion
      (DRG) neurons and the co-culture of the two cells were established before the
      test. The toxicity of ACR on nerve cells was measured by MTT. Intracellular
      calcium concentration was examined for the protection of Schwann cells. RESULTS:
      Toxic symptoms of female were occurred obviously at cumulative dose (300-400
      mg/kg). The reparative changes were found significantly after recovering 4 to 5
      weeks. The signals of S-100beta were weakened after exposure. But within the
      extended recovery period, its positive signals were gradually increased in
      consistent with the decrease of toxic symptoms. The changes of Synapsin-I were
      consistent with that of S-100beta. Compared with non co-cultured neurons, co
      cultured neurons have significant lower intracellular calcium concentration
      injured by acrylamide. CONCLUSION: The calcium channel of Schwann cells effects
      on the repair of peripheral nerve which is injured by acrylamide and Synapsin-I
      may be a key role site.

PMID- 20047214
TI  - [Synthesis and identification of artificial antigen to the common moiety of some
      organophosphorus pesticides].
AB  - OBJECTIVE: To develop an immunoassay for multiple residues of organophosphorus
      pesticides. METHODS: The generic hapten O, O-dimethyl-O-(4-carboxyphenyl)ester
      (HP) was synthesized by the reaction between O, O-Dimethyl
      phosphorochloridothionate and 4-hydroxybenzoic acid methyl ester, and then
      conjugated to bovine serum albumin (BSA) by active ester method for immunogens
      and ovalbumin (OVA) by mixed anhydride reaction for coating antigens. RESULTS:
      The hapten was synthesized successfully, which was characterized by MS. The
      coupling ratios were 15.6:1 (HP-BSA) and 16.2:1(HP-OVA), respectively, calculated
      by UV spectrophotometry. CONCLUSION: suggested that the artificial antigens could
      be used for production of broad specificity anti-organophosphorous pesticides
      antibody.

PMID- 20047213
TI  - [Metabolic activation of benzo(a)pyrene enhanced transformation of human
      bronchial epithelium cell HBETR].
AB  - OBJECTIVE: To study the application of different metabolic activation systems in
      benzo(a)pyrene [B(a)P]-induced human bronchial epithelium cell HBETR
      transformation. METHODS: In vitro metabolic activations of B(a)P were compared
      with rat liver S9 fraction mix, overexpression of a key enzyme (P450 CYP1A1), and
      prior low dose B(a)P (1 micromol/L) induction. Using soft agar assay and
      tumorigenicity assay, the different metabolic activation systems were compared to
      the influence on transformation of human bronchial epithelium cell HBETR.
      RESULTS: Both immunoblotting and enzyme activity showed that cells overexpressing
      CYP1A1 (HBETR-1A1) and 48 h after low dose B(a)P induction (HBETR-IN) had high
      level expression of CYP1A1. There were no obvious changes in the biology
      characteristic of these cells. The latencies of cell transformation in HBETR-1A1
      and HBETR-IN cells were 11 weeks when cells were treated with B(a)P at
      concentration of 20 micromol/L, while it took 14 weeks to achieve cell
      transformation in their control cells. The latencies of malignant transformation
      in HBETR cells in presence or absence of S9-mix were 14 weeks and 20 weeks,
      respectively. The efficiencies of cell transformation were in consonance with the
      protein level of endogenous CYP1A1 enzyme and its enzyme activity. CONCLUSION:
      The three metabolic conditions of the addition of rat liver S9 fraction mix,
      overexpression of a key enzyme (CYP1A1), and low dose B(a) P induction could
      enhance the B(a)P metabolic activation and shorten the latency of malignant
      transformation. In terms of the feasibility, difficulty of manipulation,
      stability, and reliability, low dose B(a)P induction could seem to be a
      prospective system used in metabolic activation in comparison with rat liver S9
      fraction mix addition.

PMID- 20047215
TI  - [Studies on performance standard for hemolytic toxins in harmful bloom algae].
AB  - OBJECTIVE: To explore a performance standard for hemolytic toxins in harmful
      bloom algae. METHODS: Using Chattonella marina as hemolytic substances producing
      organism, methods and conditions were compared and optimized including cell
      breakage, distillation temperature, blood origin and storage of algal pellets in
      extraction and activity determination of hemolytic toxins. RESULTS: The hemolytic
      activity of C. marina broken by supersonic method was 288.23 HU/L, higher than
      that by freezing--thawing method (94.89 HU/L), suggesting that supersonic method
      could be more optimal to break microalgal cells. When the supersonic treatment
      times were 5, 10, 20 and 30 min, the hemolytic activities were 80.57, 157.45,
      288.23 and 279.17 HU/L, respectively, indicating that 20 min of supersonic
      treatment was suitable. When the distillation temperature were 40, 60 and 80
      degrees C, the hemolytic activities were 288.23, 124.97 and 120.68 HU/L,
      respectively, meaning that high distillation temperature in extraction of
      hemolytic substances lowed the hemolytic activities of samples. Bloods from
      various animals such as human, fish, rat and rabbit exhibited different
      sensitivity to the hemolytic toxins, of which rabbit erythrocyte was the most
      sensitive. The hemolytic activities to human, fish, rat and rabbit were 244.98,
      288.23, 266.35 and 195.47HU/L, respectively. The storage of algal pellets for 3
      days at the temperature of 0 degrees C did not reveal a significant loss in
      hemolytic activity, while significant losses were observed at the temperature of
      20 degrees C or -20 degrees C only after one day. CONCLUSION: Supersonic method
      could be more optimal to break cell in comparison with freeze-thaw method.
      Optimal conditions for broken algal cells by supersonic method were 200 W for 20
      min at the temperature of 4 degrees C. The distillation temperature in extraction
      of hemolytic substances should be maintained under the temperature of 40 degrees
      C. The rabbit erythrocyte could be the most optimal blood to detect hemolytic
      activity due to its high sensitivity. The algal pellets could be kept at the
      temperature of 0 degrees C for 3 days before determination of activity.

PMID- 20047216
TI  - [Study on development of the principles for determination and evaluation of
      antimicrobial effectiveness of food preservatives].
AB  - OBJECTIVE: To establish the principles for determination and evaluation of the
      preservative properties demonstrates the effectiveness of a substance when used
      as a food preservative. METHODS: Sorbic acids were chosen as the model food
      preservative and the Gram positive bacterium Staphylococcus aureus, Gram negative
      bacteria Escherichia coli and Salmonella enteritidis, yeast Candida albicans and
      the filamentous fungus Aspergillus niger, A. flavas, Geotrichum candidum,
      Penicillium islandicum and Peniciuium cyclopium were employed as the experimental
      microorganisms. The test involves adding fresh and active cultures standardized
      to a concentration between 10(2) and 10(5) cfu/ml directly to sorbic acid
      solution at different concentrations ranged from 0.25 to 2 g/L to simulate
      contamination. The mixture was held for two days and microorganism survivals were
      monitored at regular intervals of 3, 6, 24 and 48 h, respectively. RESULTS:
      Sorbic acids were active against an extensive range of bacteria, yeasts and
      molds. The inhibition got stronger and stronger with either the extension of time
      against microorganisms or the increasing in concentration of sorbic acid. The
      antibacterial activity of sorbic acid were a little bit stronger than its
      antimycotic activity, with the lower minimum inhibitory concentration and the
      shorter inhibitory time in bacteria than those in fungi. In general, Gram
      negative bacteria were more sensitive to sorbic acid than Gram positive one.
      CONCLUSION: The experimental design could be science-based, sound and available
      in evaluation of the antimicrobial effectiveness of food preservatives.

PMID- 20047217
TI  - [Study on rapid detection techniques of PCR-ELISA for Listeria monocytogenes].
AB  - OBJECTIVE: To develop rapid PCR-ELISA methods for detecting Listeria
      monocytogenes, and detect food samples artificially contaminated with Listeria
      monocytogenes. METHODS: Specific primers for Listeria monocytogenes pathogenic
      gene hlyA were selected based on the Genbank data by using molecular biological
      software DNAman6.0. Digoxigenin-labeled hlyA fragments were obtained by using
      commercial kit. Specific capture probes were obtained by comparing bacterial
      pathogenic gene sequences in the Genbank. PCR-ELISA methods were developed and
      the Listeria monocytogenes isolates with different serotypes were detected. The
      sensitivity of PCR and PCR-ELISA was determined by artificially inoculating
      Listeria monocytogenes strains in milk. RESULTS: It took 6 hours to detect
      Listeria monocytogenes in food samples by PCR-ELISA. The accordance rate to the
      bacteriological method was 100%. After 12 h pre-enrichment, the detection limit
      of PCR-ELISA method was 1 CFU/25 ml milk. The sensitivity of PCR-ELISA method was
      10-100 times as PCR. CONCLUSION: The PCR-ELISA method for rapidly detecting
      Listeria monocytogenes was established. The sensitivity, specificity and
      reliability of the method proved to be good. It would be valuable to improve the
      precaution and prediction abilities of food-borne diseases and enhance the
      chronergy and accuracy of detection method.

PMID- 20047218
TI  - [Micronucleus rate and chromosome aberration of mouse embryo liver induced by
      formaldehyde].
AB  - OBJECTIVE: To study the micronucleus rate and chromosome aberration of mouse
      embryo liver induced by formaldehyde. METHODS: The pregnant mice (been pregnant
      for 13 days) were divided into 5 groups randomly: Formaldehyde was given as
      intraperitoneal injection (0.00, 0.20, 2.00, 20.00 mg/kg) for exposure group and
      Cyclophosphamide (30 mg/kg) for positive control group. When the 14th days (i.e
      After exposed in formaldehyde 18 hours), escapes the cervical vertebra cervical
      killed off pregnant mouse, peels on both sides of the uterus, takes an embryo
      respectively each side, beheads and emits the circumference blood, takes out the
      embryo liver, performs micronucleus experiment and chromosome aberration
      experiment by use of embryo liver, validate embryo liver blood micronucleus rate
      and the chromosome distortion factor. RESULTS: The micronucleus rate and
      chromosome aberration (mainly for chromosome breakage, polyploid) rate of
      embryonic liver showed significant differences in formaldehyde exposure group
      (2.00, 20.00 mg/kg) compared with the control group (P < 0.01). CONCLUSION: The
      micronucleus rate and chromosome aberration of mouse embryos liver induced by
      formaldehyde.

PMID- 20047220
TI  - [Meta analysis of effects on maternal passive smoking during pregnancy on fetal
      low birth weight].
AB  - OBJECTIVE: To analyze the effect of passive smoking of pregnancy women in early
      pregnancy and different stages during pregnancy on fetal Low-Birth-Weight.
      METHODS: Meta analysis was applied to analyze the relationship between maternal
      passive smoking during pregnancy and fetal low-birth-weight. NCBI, OVID-MEDLINE,
      CNKI, VIP and CBM were searched with the language limited to Chinese and English.
      The search was finished in April 2008. Pooled ORs with 95% CI were estimated.
      RESULTS: Totally, 26 papers were got, including 20 cohort studies and 6 case
      control studies. Maternal passive smoking was associated with an increased risk
      of low-birth-weight. The unadjusted pooled OR was 1.65 (95% CI = 1.39-1.97), and
      the adjusted pooled OR was 1.60 (95% Ci = 1.25 - 2.05). The pooled OR of exposure
      with lowest and highest level were OR = 1.53 (95% CI: 1.14 - 2.04)and OR =
      2.53(95% CI: 1.46-4.36), respectively. The pooled OR of exposure at early
      pregnancy was 1.12 (95% CI = 0.82-1.55), with no statistically significance.
      CONCLUSION: Maternal passive smoking during pregnancy could increase the risk of
      delivering a low birth-weight baby. Middle or late pregnancy might be the
      sensitive period of passive smoking's effect. Whether passive smoking' s
      threshold effect exists or not is still not sure.

PMID- 20047219
TI  - [Meta-analysis of the effects on hormone replacement therapy and oral
      contraceptives associated with female lung cancer risk].
AB  - OBJECTIVE: To evaluate the effects of hormone replacement therapy (HRT) and oral
      contraceptives (OCs) on lung cancer risk in women. METHODS: We retrieved studies
      by systematically searching Medline and other computerized databases. Pooled odds
      ratios (OR) were appropriately derived from fixed-effects or, in the presence of
      heterogeneity, random-effects models. RESULTS: Twelve studies were identified
      including 3 cohort studies and 9 case-control studies. The OR value associated
      with HRT was 0.88 (95% CI: 0.77-1.01). Subgroup analyses by smoking revealed that
      the OR value associated with HRT in smokers' and non-smokers' women were 0.76(95%
      CI: 0.61-0.95) and 0.78 (95% CI: 0.64-0.95), respectively. There was no
      statistical relationship between lung cancer risk and OCs (OR = 0.95; 95% CI:
      0.83-1.20). CONCLUSION: The results suggest a potential decreased risk of female
      lung cancer might be associated with HRT. Additional well-designed studies are
      warranted to validate these findings.

PMID- 20047221
TI  - [Meta-analysis of effect of intervention with folic acid on neural tube defects].
AB  - OBJECTIVE: To provide evidences for decision-making on neural tube defects
      prevention according to evaluating the effect of intervention with 0.4 mg folic
      acid on the incidence of neural tube defects in China. METHODS: Meta-analysis
      with software of Review Manager 4.2 version was used to synthetically and
      quantitatively evaluate the studies included. The Peto method of fixed effect
      model and random effect model (DerSimonin and Laird) were applied to estimate
      combined effect values and their corresponding 95% confidence intervals of
      homogenous and inhomogenous data respectively. RESULTS: Six pieces of literature
      included in which the studies were folic acid intervention were inhomogenous
      (chi2 = 13.43, P = 0. 02). Random effect model of Meta-analysis method were used.
      The combined effect values of intervention with folic acid on neural tube defects
      among women were strikingly significance (Z = 5.17, P = 0.00001). The pooled RR
      values were 0.36 (95% CI: 0.25-0.53). CONCLUSION: Intervention with folic acid on
      neural tube defects are effective.

PMID- 20047222
TI  - [Effect of pregnancy rats supplemented with docosahexaenoic acid on carnitine
      palmitoyl transferase-I gene expression in offspring].
AB  - OBJECTIVE: To investigate the effect on lipid metabolic and carnitine palmitoyl
      transferase-I (CPT-I) gene expression of offspring when their maternal rats
      supplemented with docosahexaenoic acid (DHA) during pregnancy. METHOD: Female SD
      rats were randomly divided into A, B, C groups. Group A was fed with basic diet,
      group B was supplemented with low dose of DHA, and group C supplemented with high
      dose of DHA during pregnancy. All the male offspring were suckled by maternal
      rats in group A. Offspring were fed with basic diet from weaning (week 3) to week
      8. Body weight, body fat, triglycerides (TG), total cholesterol (TC), high
      density lipoprotein (HDL-C) and CPT- I mRNA level were observed in eight rats of
      every group. RESULTS: The birth body weights in three groups of offspring of rats
      were no significantly difference(P > 0.05). At the end of 8 weeks, the body
      weights in group C was significantly lower than that of the group A/P < 0.05),
      then the body fat, TG in B and C were significantly lower than those of group A
      (P < 0.05), but HDL-C in C were significantly higher than those of group A (P <
      0.05), but the TC was no significant difference in three groups. The CPT-I mRNA
      levels in B and C were persistently higher than those of group A during
      experiment. CONCLUSION: Supplementation with DHA during pregnancy mediate fatty
      acid oxidation and decrease blood lipid in offspring that could persistently
      increase CPT-I gene expression. But excess DHA consumption during pregnancy could
      cause adverse health effects in offspring.

PMID- 20047223
TI  - [The relationship between anemia and physical development among children at the
      ages of 3-6 years in 21 counties of China].
AB  - OBJECTIVE: To explore the relationship between anemia and childhood growth among
      preschool children. METHODS: The data were from the records of Children Follow-up
      Study Project carried out by Institute of Reproductive and Child Health of Peking
      University and the records of related perinatal health care surveillance system
      in 21 counties/cities of Hebei, Jiangsu and Zhejiang provinces. These children
      were divided into three groups based on the hemoglobin concentration-non-anemia
      group, mild anemia group and middle & grave anemia group. The body height, body
      weight, BMI, HAZ, WAZ, stunting rate and underweight rate of each group were
      compared. RESULTS: The body height and body weight of each anemia group were
      significantly lower than those of non-anemia group. For each group of the anemic
      boys at the ages of 3-, 4-, 5-, 6-7 years, their body heights were averagely
      shorter by 0.65, 0.69, 0.94 and 1.42 cm and their body weights were averagely
      lighter by 0.22 kg, 0.18 kg, 0.38 kg, 0.63 kg than those of non-anemic boys
      respectively. As for anemic girls at the ages of 3-, 4-, 5-, 6-7 years, the body
      height gaps were 0.93, 0.74, 0.88 and l.7lcm and body weight gaps were 0.29,
      0.22, 0.35 and 0.78 kg respectively. The anemic children were at higher risk for
      stunting (OR = 1.37) and underweight (OR = 1.32) after adjusting for birth
      weight, urban & country district, maternal height, maternal BMI at the first
      prenatal visit, maternal education and occupation. CONCLUSION: There was a
      significant correlation of growth retardation with childhood anemia, and more
      efforts should be made to prevent and treat childhood anemia in order to promote
      children growth.

PMID- 20047224
TI  - [Effects of low-iron intervention in pregnant rat on hematology parameters of
      adulthood offspring].
AB  - OBJECTIVE: To explore the effect of low-iron intervene in pregnant rat on
      hematologic parameters of its offspring in adulthood. METHODS: Wistar female rats
      at the age of six weeks were divided into two groups randomly: experimental group
      were feeded with low-iron diet, control group were feeded with iron-sufficient
      diet. They were mated with healthy male rats after four weeks and the iron
      intervention were carried out until the lactation period end. Iron-sufficient
      diet were then given to all rats for ten weeks and this period were called iron
      balancing period. After that control group and experimental group were divided
      into two groups respectively and all the rats were killed to detect Hb, RET, RDW,
      FEP, SI, SF, TIBC et al after sixteen weeks. RESULTS: Iron intervention in
      pregnant rats resulted in the iron deficiency of their offspring. In comparison
      with control group, Hb and RET of the offspring whose mother feeded with low
      level iron diet in pregnancy were significantly elevated after four and six weeks
      in intervention again. While TIBC were also higher than those of control when
      intervention period was ended. CONCLUSION: Iron deficiency during pregnant rats
      produce long-dated affect on iron intake of their offspring in growth phase and
      adulthood, but it did not show stronger capability of anti-anemia than control
      rats.

PMID- 20047225
TI  - [The influence of the nutrient supplement for children on the nutrition and
      health status and intelligence of children of schooling age in the countryside of
      children of schooling age during 2 years].
AB  - OBJECTIVE: To analyze the effect of complex nutrients on growth and development,
      intelligence and nutrition state of 6-12 years old children in two continuous
      years. METHODS: According to the rural school's similar condition, such as social
      economical statement, education condition and proportion of students entering
      schools, 6 rural schools were respectively selected in Xishui County of Hubei
      Province as the experimental group and control group. In the former, middle and
      later periods (2004, 2005, 2006 ), growth and development, nutrition state and
      intelligence were analyzed and compared. RESULTS: The increase of height and
      weight in experimental group were higher than those of the control group. In 2
      years, height in experimental group increased 12.9 cm, while the control group
      increased 11.5 cm. Weights increased in experimental group were 6.6 kg, while the
      control group increased 5.2 kg. Girl's bone density in experimental group
      increased from 0.236 g/cm in 2004 to 0.280 g/cm in 2006. The hemoglobin contents
      of 4 age group's children in experimental group increased significantly (P <
      0.05) . While the anemia prevalence decreased 25 .8% in 2 years, the control
      group decreased 7.2%. Moreover, other results showed that the complex nutrients
      also have some effect on the intelligence in experiment group. CONCLUSIONS: The
      complex nutrients supplement could improve the rural school children's growth and
      development, bone and intelligence.

PMID- 20047226
TI  - [A survey of health effects on population exposure to a dust event in Beijing
      City].
AB  - OBJECTIVE: To assess the acute health effects of the population exposure to a
      dust event in Beijing. METHODS: A total of 845 children from 4 primary schools
      and 1653 adults were investigated in Beijing by the questionnaires during a dust
      event in the spring of 2005. The symptoms, such as upper respiratory and stimuli
      symptoms, were recorded daily. The daily air pollution (PM10, NO2 and SO2) data
      were monitored at the same time. The association between the concentrations of
      air pollutants and the incidence of symptoms in exposed population were analyzed
      by multiple regression models. RESULTS: Positive associations were found between
      the PM15 concentrations and respiratory symptoms both in children and adults
      during the dust event. The children were more susceptible than adults to air
      pollution. CONCLUSION: The dust events could have adverse effect on human
      respiratory health. There were positive association between increased ambient air
      PM10 concentration and incidence of upper respiratory symptoms.

PMID- 20047227
TI  - [The analysis of the present situations of smoking habits in the Hui minority
      primary school students in the backward region of Ningxia].
AB  - OBJECTIVE: To find out the current situations of smoking habits in the Hui
      minority primary school students that have in the backward region and the
      different situations between the suburb region and the rural area. METHODS: 512
      Hui minority primary school students were choosed from grade one to grade five of
      four different primary schools in 20 classes in the township of Yuanzhou
      District, Guyuan City, Ningxia Province. The preliminary investigations on the
      situations were carried out to find out the elements which affect the students on
      learning to smoke or becoming negative smokers. RESULTS: The youngest smoker was
      at the ages of 6 years Hui minority primary school student. The total percentages
      of smoking were 23.4%, and the rates went up as their grades raise. While the
      rates of the negative smokers takes 62.7%, and the rates in suburb region were
      more higher than those in the rural area (chi2 = 4.25, P < 0.05). The rates of
      the Hui minority primary school students, from the suburb and the rural areas,
      whose families had smokers were 57.5% and 46.7% respectively (P < 0.05). The
      first cigarette for those students who learning to smoke in the suburb and the
      rural area usually came from their family, from their classmates or friends. And
      these three main sources are equal one another. Among all the negative smokers in
      the suburb and the rural area, the rates of getting the cigarettes from their
      families takes 52.2% and 73.7% respectively, with statistical significance (chi2
      = 23.72, P < 0.005). In case of the awareness about the harm from smoking,
      although the rates of students that realise it takes 90% in the suburb and the
      rural areas, their awareness and attitudes towards the harm from negative smoking
      are both a little bit poor, but this awareness in the suburb region is still
      better than in the rural area. CONCLUSION: The rates of possible smokers among
      the Hui minority primary school students in the backward region of Ningxia
      Province were more higher. And it has a close relationship with their living
      environment.

PMID- 20047228
TI  - [The study on pulmonary tuberculosis knowledges and its influencing factors among
      middle school students of Three-Gorges Reservoir in Chongqing].
AB  - OBJECTIVE: To investigate the pulmonary tuberculosis knowledge and its
      influencing factors among middle school students of Three-Gorges Reservoir
      poverty county in Chongqing, in order to provide basis for health education of
      tuberculosis knowledges. METHODS: 1639 middle school students were randomly
      collected and surveyed by self-developed questionnaire, which mainly concerned
      about tuberculosis relevant knowledge. Chi2 test and logistic stepwise regression
      analysis were utilized to study the major factors affecting pulmonary
      tuberculosis knowledge of middle school students. RESULTS: Overall awareness
      rates on tuberculosis relevant knowledge of Middle school students in the
      reservoir area were 31.1%. Average scores of tuberculosis relevant knowledge were
      5.95 +/- 3.47. Multivariate non-conditional logistic regression analysis
      identified that 6 factors had significant influence on score of knowledge part (P
      < 0.05), including grade, gender, home location, education level of father,
      family tuberculosis history, and family economic status. The students' knowledge
      were mainly learned from broadcasting, TV programs (69.4%), books, magazines,
      newspapers (56.9%), and tuberculosis preventive education booklet or leaflets
      (44.7%). CONCLUSION: The key steps of promoting middle school students' overall
      awareness rate on tuberculosis relevant knowledge should include enhancement of
      relevant health education, the improvement of parental educational level, and the
      development of economy.

PMID- 20047229
TI  - [Relationship between tea-drinking and anaemia of rural reproductive married
      women in a community-based cross-sectional study in China].
AB  - OBJECTIVE: To determine the prevalence of anaemia and the relationship between
      tea-drinking and anaemia in reproductive married women in rural China. METHOD: A
      cross-sectional study was carried out in four rural communities in Deqing County,
      Zhejiang Province, China. A total of 1425 reproductive married women at the ages
      of 20 to 49 years participated in this study and had a satisfactory measure of
      hemoglobin. Their general information, health status and lifestyle behaviors were
      collected. Hemoglobin was tested by Drabkin Method. Chi-square test, and binary
      and multinomial Logistic regression models were used for statistical analysis in
      SPSS 11.0. RESULT: Among 1425 subjects, the average concentration of hemoglobin
      were 114.7 +/- 17.0 g/L, the prevalences of anaemia were 63.3%, and most were
      mild and moderate anaemia (Such prevalence were 63.5%, 63.2% and 63.4%
      respectively at the ages of 20-30 years, 31-40 years, and 41-49 years.). Subjects
      with tea-drinking were higher in average concentration of hemoglobin than those
      of no tea-drinking (t = 3.33, P = 0.001). There were significant associations
      between tea-drinking and anaemia OR was 0.56 (95% CI: 0.45, 0.73). Further, such
      protective effects of tea-drinking were observed among subjects with different
      anaemia [ORs were 0.57 (95% CI: 0.43, 0.75), 0.57 (95% CI: 0.43, 0.75), and 0.28
      (95% CI: 0.11, 0.70)] in mild, moderate and severe anaemia, respectively.
      CONCLUSION: The prevalence of anaemia in reproductive married women in rural of
      China could be higher and tea-drinking could be a possible protective factor.

PMID- 20047230
TI  - [Level of microwave radiation from mobile phone base stations built in
      residential districts].
AB  - OBJECTIVE: To investigate the condition of microwave radiation pollution from
      mobile phone base station built in populated area. METHODS: Random selected 18
      residential districts where had base station and 10 residential districts where
      had no base stations. A TES-92 electromagnetic radiation monitor were used to
      measure the intensity of microwave radiation in external and internal living
      environment. RESULTS: The intensities of microwave radiation in the exposure
      residential districts were more higher than those of the control residential
      districts (p < 0.05). There was a intensity peak at about 10 m from the station,
      it would gradually weaken with the increase of the distance. The level of
      microwave radiation in antenna main lobe region is not certainly more higher than
      the side lobe direction, and the side lobe direction also is not more lower. At
      the same district, where there were two base stations, the electromagnetic field
      nestification would take place in someplace. The intensities of microwave
      radiation outside the exposure windows in the resident room not only changed with
      distance but also with the height of the floor. The intensities of microwave
      radiation inside the aluminum alloys security net were more lower than those of
      outside the aluminum alloys security net (p < 0.05), but the inside or outside of
      glass-window appears almost no change (p > 0.05). CONCLUSIONS: Although all the
      measure dates on the ground around the base station could be below the primary
      standard in "environment electromagnetic wave hygienic standard" (GB9175-88),
      there were still a minorities of windows which exposed to the base station were
      higher, and the outside or inside of a few window was even higher beyond the
      primary safe level defined standard. The aluminum alloys security net can partly
      shield the microwave radiation from the mobile phone base station.

PMID- 20047231
TI  - [A experimental study on the effect of fluorine capture of calcium based coal
      briquette].
AB  - OBJECTIVE: To study on the fluorine capture effect of calcium based coal
      briquette with fluorine capture additive in coal-burning fluorosis area. METHODS:
      Add proper proportions of calcium based fluorine capture additive in high
      fluorine coal for making coal briquette were added, and were added the fluorine
      in coal cinder in order to reduce its emission. Meanwhile, to determine the
      composes of coal briquette were added, the percentage of fluorine in coal cinder
      and the concentration of fluoride, sulfur dioxide and PM10 were determinated, to
      evaluate the effect of fluorine capture and the level of door air pollution.
      RESULT: After pilot-scale studying on the effect of fluorine capture in 30
      households at coal-burning fluorosis area in Guiding of Guizhou Province. The
      average fluorine capture rate were 71.8%, and the average concentration of
      fluoride were 0.0052 mg/m3, which reduces by 27.8% in comparison with control
      group and were lower than environmental air quality standard (0.007 mg/m3); and
      the average concentration of SO2 were 0.67 mg/m3, which reduces 52.8% in
      comparison with control group and slightly higher than those of indoor air
      quality standard (0.5 mg/m3). CONCLUSION: The application of the coal briquette
      made by calcium based fluorine capture additive could reduce the pollution caused
      by high fluorine coal, could improve the quality of indoor air.

PMID- 20047232
TI  - [Study on reproductive and immune toxicity of male rats exposed to As2O3].
AB  - OBJECTIVE: To study on reproductive and immune toxicity of male rats exposed to
      subacute As2O3. METHODS: 24 male rats of KM-strain were divided into four groups
      and were given by gavage deionized water, 2.0, 4.0 and 8.0 mg As/(kg x bw) for 7
      days. After the exposure, the rats were killed and the testis, epididymis were
      collected and analysed. RESULTS: (1) In comparison with control, testicular and
      epididymal weights were lower than those of high dose group (P < 0.05), but there
      were no difference of testicular indexes between exposed group and control. The
      stained sperm count were lower than those of arsenic exposure group (P > 0.05),
      and malformation rate of sperm were significant increase in middle- and high-dose
      group (P < 0.05); (2) Compared to control, the weight and index of immune organ
      was decrease in middle-and high-dose group, and the spleen weight and index was
      significantly lower in high-dose group (P < 0.05). CONCLUSION: As2O3 can induce
      reproductive and immunotoxicity in male mice.

PMID- 20047233
TI  - [Effects of high-sugar and high-fat diet on growth and carbohydrate, lipid
      metabolism in Wistar rats].
AB  - OBJECTIVE: To study the effects of high-sugar and high-fat diet on the growth and
      carbohydrate, lipid metabolism of Wistar rats. METHODS: According to their weight
      and fasting blood glucose, twenty male Wistar rats were randomly divided into 2
      groups (n = 10): control group and experimental group, and were fed by normal
      diet and high-sugar and high-fat diet respectively for 6 weeks. The growth curve
      of rats and food utilization were observed, the parameters of carbohydrate and
      lipid metabolism were measured. RESULTS: After 6 weeks feeding, the body weight,
      food utilization, body weight accounted for the percentage of visceral fat, serum
      total cholesterol and low-density lipoprotein cholesterol of experimental group
      were significantly higher than those of control group (P < 0.05), and serum high
      density lipoprotein cholesterol of experimental group was significantly lower
      than that of control group (P < 0.01) . The fasting plasma glucose (FPG) of two
      groups was no significant difference. The glucose tolerance of experimental rats
      was impaired, the area under the curve of glucose was significantly higher than
      that of control rats. CONCLUSIONS: High-sugar and high-fat diet could cause the
      enhance of central accumulation of body fat, and increased serum total
      cholesterol, resulting in decreased glucose tolerance ability for type 2 diabetes
      in the process of an important risk factor.

PMID- 20047234
TI  - [Effect of broken black tea on the formation of dental enamel and the contents of
      twelve kinds of chemical elements].
AB  - OBJECTIVE: The aim of this study was to investigate the effect of broken black
      tea with slightly hyper-normal fluoride content which was near the level of
      people tea-drinking habits on enamel morphological structure and its content of
      chemical elements. Thirty six rats were divided randomly into 3 groups: one was
      control group and another two groups fed with broken black tea infusion with F-
      content of 8.2 mg/l and 16.4 mg/l, respectively. After 360 days, collected 144
      teeth, observed their morphological structure by electron micrograph, Scanning
      electron micrographs (SEM) and also analyzed concentrations of several chemical
      elements in tooth by x-ray fluorescence spectrometry (XRF). Chronic dental
      fluorosis in rats was induced by treatment with broken black tea with slightly
      hyper-normal fluoride content. Hyper-calcification and hypo-calcification
      appeared in enamel of those teeth from both broken black tea treated groups in
      dose-dependent manner. Twelve kinds of chemical elements, such as Ca, Mg, P, Al,
      Cl were examined. The contents of Ca, P, Mg were reduced and that of Al and Cl
      were increased significantly. Compared with control group, the levels of Si, S,
      Fe were lower in those teeth from treated group (broken black tea with the F-
      content of 8.2 mg/l), while higher in those teeth from treated group (broken
      black tea with the F- content of 16.4 mg/l). Long-term drinking broken black tea
      with hyper-normal fluoride content could cause chronic dental fluorosis, and its
      injury in enamel was related with Hyper-calcification and hypo-calcification
      mainly. Those changes of several chemical elements level in enamel, such as Ca,
      P, Al, Cl, were suggested that these chemical elements have influences on the
      development and mineralization of enamel.

PMID- 20047235
TI  - [Synthesis and identification of sulfonamides artificial antigen].
AB  - OBJECTIVE: To synthesise N-sulfanil-4-aminobutyric acid mother nucleus derivative
      of sulfonamides, and its artificial antigens in order to explore the methods of
      preparation were discussed. METHODS: N-sulfanil-4-aminobutyric acid was
      synthesized and confirmed by 1HNMR, 13CNMR, IR, ESI-MS. N-sulfanil-4-aminobutyric
      acid artificial antigen was synthesized by the methods of active ester coupling,
      and was identified by UV scan. Single factor test and orthogonal test design
      methods L9(3(3)) were employed to study the influence of the factors such as the
      initial molar ratio of reagents, activate hapten time and the coupling time to
      the coupling rate, as to determine the optimal reaction conditions for synthesis.
      The obtained results showed that the initial molar ratio of hapten to BSA 50:1,
      activated hapten time 6 hours, coupling time 4 hours. The artificial antigen was
      prepared by the optimal reaction conditions. The artificial antigen was injected
      into Balb/c mice and the blood samples were obtained from tails of Balb/c mice
      after the 5th injection and detected by iELISA method. RESULTS: The structure of
      N-sulfanil-4-aminobutyric acid was correct. The artificial antigen was prepared.
      CONCLUSION: Antigens was acquired successfully.

PMID- 20047236
TI  - [Effect of an active component from Forsythia suspensa (Thunb.) Vahl against
      respiratory syncytial virus in vitro].
AB  - OBJECTIVE: To study the extraction of an active component LC-4 from Forsythia
      suspensa (Thunb.) Vahl and anti-respiratory syncytial virus (RSV) effect in
      vitro. METHODS: The extration from boiling water of Forsythia suspensa were
      extracted by hot water extraction and were precipitated by ethanol and were
      elicited by macroporous adsorptive resins column chromatography. Then the
      antiviral active component LC-4 was separated from the production by eluting. The
      cytotoxicities and antiviral effect of LC-4 were tested by the Neutral Red assay
      and the cytopathic effect (CPE) inhibition assay. Ribavirin was used as the
      positive drug in the study. The antiviral effect of prevention and treatment of
      maximum dose of non-cytotoxicity of LC-4 was tested in Hela cell line. RESULTS:
      LC-4 showed that the concentration were 25.4 microg/ml with the medium
      cytotoxicity and were 2.11 microg/ml with the medium effective concentration
      (EC50). The corresponding treatment index of LC-4 was 12.04. It also exhibited
      obviously inhibition effect on RSV replications when LC-4 was added at 2 h, 4 h,
      6 h and 8 h after infection (P < 0.05). The CPE was significant difference in
      comparison with control group, when the concentration of LC-4 between 31.25
      microg/ml and 3.91 microg/ml was added at 2 h before infection (P < 0.05).
      CONCLUSION: LC-4 could significantly prevent and inhibit RSV replications in
      vitro.

PMID- 20047237
TI  - [Optimization of the REP-PCR molecular classification method of Salmonella and
      its application in drug-resistant strains].
AB  - OBJECTIVE: To optimize the reaction conditions of REP-PCR molecular
      classification method of Salmonella; primarily apply it in drug-resistant
      strains, and supply data to a system of Salmonella homology tracing. METHODS:
      Genomic DNA of Salmonella enteritidis 510041 was used as the template for PCR.
      Target sequences in 510041 genomic DNA were amplified with the primers designed
      according to the references. To optimize template concentration, Mg2+
      concentration, primers concentration of PCR, the factor to be optimized was
      designed in different concentration grads and other factors were fixed. The REP
      PCR fingerprint maps of 24 strains of Salmonella epidemic drug-resistant isolates
      were analyzed with the optimum reaction conditions. The 24 strains of Salmonella
      epidemic drug-resistant isolates were classified according to their fingerprint
      maps, and the classification results were compared to classification results form
      drug-resistant spectrum. RESULTS: The fingerprint map bands were most clear when
      25 microl of the reaction system contained 100 ng template, 2.0 mmol/L Mg2+ and
      0.4 micromol/L each primer. The REP-PCR fingerprint maps of different serotypes
      and serum clusters of Salmonella were different. The amplification products
      contained 2 to 6 bands, whose length were between 0.5 kb to 2.5 kb. The 24
      strains of Salmonella isolates were classified in 15 types according to
      fingerprint maps and 7 types according to drug-resistant spectrum. CONCLUSION:
      The optimum REP-PCR molecular classification method of Salmonella was established
      fingerprint maps classification method was more sensitive than drug-resistant
      spectrum classification method.

PMID- 20047238
TI  - [Study on simultaneous determination method for banded synthesis hormones
      residues in egg products].
AB  - OBJECTIVE: To develop method of 7 banded synthesis sex hormones residues in egg
      products determined by ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS). METHODS: The sample were enzymolied and target
      compounds were extracted with methanol. ZnCl2 was added to the extract solution
      to remove lipid and then analytes were purified by LC-C18 and LC-NH2 solid phase
      extraction cartridge and further determined by UPLC-MS/MS under positive
      ionization and multiple reaction monitoring (MRM) modes. RESULTS: The limits of
      detection (LOD) of UPLC-MS/MS method used for testing Chlormadione acetate (CDA),
      Medroxypogesterone acetate (MPA), Megestrol Acetate (MA), Testosterone propionate
      (TSP), Norgestrel (NG), Methyltestosterone (MTS) and Nandrolone (NT) in egg
      products ranged from 0.012 to 0.23 microg/kg, and the limits of quantification
      (LOQ) were from 0.04 to 0.76 microg/kg. Experiments on spiked samples of egg
      products showed that at addition level of 2.0 microg/kg, the average recoveries
      of the sex hormones ranged from 80.2% to 114%, and coefficients of variation from
      6.7% to 14.3%; while at addition level of 4.0 microg/kg, the average recoveries
      ranged from 75% to 119%, and coefficient of variation from 2.9% to 7.3%.
      CONCLUSION: The method could be able to identify and quantify banded synthesis
      hormones residues in eggs and egg products. It could be simple and sensitive,
      suitable for statutory residue testing.

PMID- 20047239
TI  - [15 rare earth elements in cosmetics determined by inductively coupled plasma
      mass spectrometry].
AB  - OBJECTIVE: To establish an ICP-MS method for the simultaneous determination of 15
      rare earth elements (REEs) in Cosmetics. METHODS: Cosmetics were digested with
      HNO3 + H2O2 by microwave oven. An interference-free isotope was chosen for earth
      REE as 89Y, 139 La, 140Ce, 141Pr, 146Nd, 147Sm, 153Eu, 157Gd, 159Tb, 163Dy,
      165Ho, 166Er, 169Tm, 172Yb, 175Lu, 15 REEs were determined by ICP-MS. RESULTS:
      The correlation coefficient r > or = 0.9998. The recovery rates and relative
      standard deviations could 89.3%-114.6% and 1.45%-7.93%. In the detection for real
      samples, La, Ce, Nd and Y were detected in creamy samples. 13 REEs in powdery
      samples, were detected except for Tm, Lu. Maybe their raw material source were
      different. CONCLUSION: The results indicated that the method could be simple,
      rapid, sensitive and accurate, which could meet the demand of the simultaneous
      determination for 15 rare earth elements analysis in Cosmetics.

PMID- 20047240
TI  - [Application of predictive microbiology in fungi growth and mycotoxin
      production].
AB  - Food spoilage and food poisoning caused by fungi is an important issue in the
      field of food safety. The linear regression equations and predictive models are
      developed through the study on the effect of environmental factors on fungi
      growth and mycotoxin production. This is easier to understand fungi activities.
      Predictive microbiology plays an important role in evaluation of food spoilage
      and food poisoning. The application of predictive modelling in fungi growth and
      mycotoxin production are reviewed.

PMID- 20047241
TI  - [The application of LC-MS/MS in measurement of oxidative stress parameters].
AB  - OBJECTIVE: Oxidative stress is frequently cited as a cause of various disease
      states. There is increasingly intense scientific and clinical interest in
      oxidative stress. However, there remain many analytical limitations to currently
      available assays for oxidative stress markers. Recent improvements in software,
      hardware, and instrumentation design have made liquid chromatography and tandem
      mass spectroscopy (LC-MS/MS) methods for the determination of many oxidative
      stress markers. In particular, LC-MS/MS could often provide the advantages of
      higher specificity, higher sensitivity, and the capacity to determine multiple
      analytes. The sensitivity limits for LC-MS/MS usually lay within the ranges of fg
      pg of analyte per LC on-column injection. In this article, the present
      capabilities of LC-MS/MS were briefly presented and some specific examples of the
      strengths of these LC-MS/MS assays were discussed. The selected examples included
      methods for isoprostanes, oxidized proteins and amino acids, and DNA biomarkers
      of oxidative stress.

PMID- 20047242
TI  - [The impacts of extreme events of weather and climate on infectious disease].
AB  - OBJECTIVE: In this paper the articles on the impacts of extreme events of weather
      and climate on infectious disease were summarized, in which were published in
      China from 1995 to 2008. Among all kinds of extreme events of weather and
      climate, flood, warm winter, high temperature and drought had the most obvious
      effect on infectious disease. In this paper, the impact on epidemic and
      activities of vectors and infectious parasites, as well as the change of
      incidence and epidemic scale of related infectious disease were respectively
      reviewed.

PMID- 20047243
TI  - Glycemic control among older adult hematopoietic cell transplant recipients.
AB  - Adults age 55 and older with hematological malignancies who require hematopoietic
      cell transplantation (HCT) for survival are at risk for a number of nonmalignancy
      related, potentially life-threatening outcomes, often due to suboptimal immune
      function. Evidence is emerging regarding how abnormal glycemic levels-newly
      termed malglycemia-impair cells of the immune system. Further, older adult HCT
      recipients appear highly susceptible to malglycemic states, particularly
      hyperglycemia, due to treatment regimens, nutritional imbalances, states of
      immobility, and stress, all coupled with the natural aging process. Patients with
      preexisting diabetes may be at further risk for malglycemic states. The growing
      number of older adults receiving HCT will substantially increase the likelihood
      nurses will have to provide care to HCT survivors. Therefore, it is important
      nurses in all practice settings have an understanding of the short-and long-term
      effects of glycemic status on immune function.

PMID- 20047244
TI  - The next generation of geriatric nurse specialists.

PMID- 20047245
TI  - Assessing the mirrors in long-term care homes: a preliminary survey.
AB  - A preliminary survey of the mirrors available to residents was conducted in 10
      long-term care homes. The framework underlying the study was Lawton's theory that
      the planned environment functions to maintain, support, and stimulate. The
      findings were discouraging. Some facilities had no mirrors available for bedbound
      residents or wheelchair users. In most facilities, a resident could not view his
      or her lower body in a mirror. The majority of mirrors were obstructed from view.
      This pilot study suggests a need for future mirror research. Implications for
      nursing are discussed, and placement of mirrors is described.

PMID- 20047246
TI  - Implementing evidence-based practice in Taiwanese nursing homes: attitudes and
      perceived barriers and facilitators.
AB  - To date, there is a paucity of research investigating nurses' perceptions of
      evidence-based practice (EBP) in nursing homes, especially in non-Western
      countries. This descriptive, quantitative study investigated attitudes toward and
      perceived barriers and facilitators to research utilization among 89 Taiwanese
      RNs. The majority of nurses expressed positive attitudes toward research and EBP.
      The most frequently cited barriers were related to insufficient authority to
      change practice, difficulty understanding statistical analyses, and a perceived
      isolation from knowledgeable colleagues with whom to discuss the research. EBP
      facilitators included improved access to computers and Internet facilities in the
      workplace, more effective research training, and collaboration with academic
      nurses. These findings are similar to those from research conducted in Western
      countries and indicate that further education and training in research for nurses
      working in nursing homes would be beneficial.

PMID- 20047247
TI  - Strategies for reducing polypharmacy in older adults.
AB  - Polypharmacy is a major concern in the care of older adults. Multiple factors
      contribute to this problem, and recognizing these factors is an initial step in
      addressing the problem. Further, identifying those individuals at risk for
      medication problems, as well as implementing specific strategies in practice to
      reduce the problem, will enable clinicians to develop safe and evidence-based
      medication regimens that minimize the risk of adverse drug reactions. The key to
      treating older adults is not necessarily to find a set number of medications and
      try to stay below it, but to find the right medication at the right dosage and
      for the shortest possible duration on a case-by-case basis. This individualized
      approach to treating patients will provide a much safer and effective means of
      practicing and will improve patients' quality of life.

PMID- 20047248
TI  - Developing a comprehensive electronic health record to enhance nursing care
      coordination, use of technology, and research.
AB  - As in acute care, use of health information technology in long-term care holds
      promise for increased efficiency, better accuracy, reduced costs, and improved
      outcomes. A comprehensive electronic health record (EHR), which encompasses all
      health care measures that clinicians want to use-both standard health care
      assessments and those acquired through emerging technology-is the key to
      improved, efficient clinical decision making. New technologies using sensors to
      passively monitor older adults at home are being developed and are commercially
      available. However, integrating the clinical information systems with passive
      monitoring data so that clinical decision making is enhanced and patient records
      are complete is challenging. Researchers at the University of Missouri (MU) are
      developing a comprehensive EHR to: (a) enhance nursing care coordination at
      TigerPlace, independent senior housing that helps residents age in place; (b)
      integrate clinical data and data from new technology; and (c) advance technology
      and clinical research.

PMID- 20047250
TI  - Exposure to the airborne mould Botrytis and its health effects.
AB  - Most investigations into the correlation between exposure to fungi and
      detrimental health effects focus on the 2-4 most prevalent genera in ambient air,
      both outdoors and indoors. Yet over 80 genera of fungi have been shown to have
      allergenic potential. Also, there is no agreement about threshold values for
      exposure to fungi. One of the fungal genera expected to be less prevalent in
      ambient air and known to cause allergy is Botrytis. In this review, we
      investigate the airborne exposure level and health effect of Botrytis, both at
      general exposure and in occupational settings. The surveyed papers show that
      Botrytis is found globally with different spore seasons depending on the region
      investigated. The levels of Botrytis in the percentage of all fungi have a
      calculated median of around 1.1% in the different environments, confirming that
      it is among the less prevalent fungi. Furthermore, a substantial proportion of
      patients and workers are allergic to Botrytis cinerea, and when B. cinerea was
      included in extended test panels additional allergic patients were found. Thus,
      B. cinerea is as important as the more prevalent mould genera Cladosporium and
      Alternaria and we suggest that it should be included in standard allergic tests
      panels.

PMID- 20047251
TI  - Important phytopathogenic airborne fungal spores in a rural area: incidence of
      Botrytis cinerea and Oidium spp.
AB  - The effects of the climatic changes more and more frequently, favour the
      emergence and the development of plant diseases. Botrytis cinerea and Oidium spp.
      spores are often responsible for enormous productivity losses in cultures with
      high commercial interests such as the grapevine. This work aims to detect these
      airborne spores, before the emergence of lesions in Vitis vinifera. In the rural
      area of Amares, the seasonal distribution of the concentration of the 2 spore
      types, was continuously studied between 1 March-31 October (2005-2007), using a 7
      day volumetric Hirst-type spore trap. These data was compared with
      phytopathological data. B. cinerea sporulation occurs in March-April while Oidium
      spp. occurs in April-May. Fluctuations were observed due to the influence of
      different meteorological factors. The emergence of the first signs of grey mould
      and powdery mildew were preceded by increments of B. cinerea and Oidium spp.
      spore concentration. The precocious detection of increasing trends in airborne
      spore concentration of B. cinerea and Oidium spp. can notify the probable onset
      of grey mould and powdery mildew leading to application of lower quantities of
      phytopharmaceutical products in the most favourable developmental stage.

PMID- 20047249
TI  - Anxiety, depression, and cognitive impairment in dementia-specific and
      traditional assisted living.
AB  - With the rapid growth of the assisted living (AL) industry, the number of AL
      residences providing dementia care continues to increase. The purpose of this
      article is to describe and compare demographic characteristics; frequency and
      type of psychiatric diagnoses; level of cognition, depression, and anxiety
      symptoms; and use of psychotropic medication among older adults in dementia
      specific assisted living (DSAL) and traditional assisted living (TAL) residences.
      Secondary analysis of screening data collected during a cross-sectional,
      descriptive pilot project compared 18 participants from two DSAL facilities and
      28 participants from three TAL facilities. DSAL participants with dementia were
      more cognitively impaired than TAL participants with dementia (p < 0.001) and
      used more antipsychotic (67%), anxiolytic (60%), antidepressant (53%), and
      cognitive-enhancing (87%) medications. No statistically significant differences
      in demographic factors or levels of anxiety or depression were observed among
      residents in either setting.

PMID- 20047252
TI  - Seroprevalence of Q fever, brucellosis and leptospirosis in farmers and
      agricultural workers in Bari, Southern Italy.
AB  - To establish the seroprevalence of antibodies to C. burnetii, Leptospira and
      Brucella in subjects at risk of exposure, 128 workers exposed to farm animals and
      280 healthy blood donors were studied. Antibodies to C. burnetii, Leptospira and
      Brucella were determined by indirect immunofluorescence assay, by
      microagglutination test (MAT) and by standard tube agglutination test,
      respectively. Of subjects exposed to farm animals 73.4 % were positive for anti
      C. burnetii IgG (titer > or = 20) compared to 13.6 % of control subjects (p <
      0.0001). The seroprevalence was found mainly among the veterinarians (100 %) and
      the animal breeding workers (84 %). The trend of percentage of positivity to
      antibodies to C. burnetii is significant only in the group of workers > or = 70
      years, when adjusted for sex and occupation. None of the subjects examined had
      antibodies to Leptospira and Brucella. Further improvements in the occupational
      hygiene of the work environment is advisable.

PMID- 20047253
TI  - Occurrence of cases of borreliosis certified as an occupational disease in the
      province of Wielkopolska (Poland).
AB  - The aim of the study was to analyze the occurrence of cases of borreliosis to
      classify as an occupational disease in the province [voivodeship] of Wielkopolska
      in the years 2000-2007. The data as a basis for this analysis originated from the
      database on the occupational disease certification created by the Public Health
      Service in Poznan. Documentation from the years 2000-2007 reviewed. The maximum
      number of the cases of borreliosis in the territory of Wielkopolska certified as
      the occupational disease fell in the years 2002-2003. In the territory of
      Wielkopolska, borreliosis as an occupational disease has been significantly more
      often certified in men. The population at the age of 41-60 prevailed in that
      case. The districts with the biggest number of certificed cases of borreliosis as
      an occupational disease include the following: Miedzychod, Poznan, Czarnkow
      Trzcianka, Gostyn, Jarocin, Leszno and Krotoszyn. Further analyses concerning
      real exposure to infection with spirochaetes Borrelia burgdorferi and its effects
      in the population of the workers of forestry and agriculture in the territory of
      Wielkopolska is recommended. It should be suspected that the epidemiologic data
      concerning the cases of borreliosis in the occupational conditions are
      understated.

PMID- 20047254
TI  - Multilevel analysis of the impact of environmental factors and agricultural
      practices on the concentration in hay of microorganisms responsible for farmer's
      lung disease.
AB  - Farmer's lung disease (FLD) is common in eastern France. It is the main form of
      occupational hypersensitivity pneumonitis, caused by chronic inhalation of
      microorganisms (antigens) from mouldy hay, straw, or grain. The purpose of this
      study was to assess, with a panel of data collected between 1997-2003,
      environmental factors and agricultural practices that independently modify
      concentrations in hay of microorganisms potentially responsible for FLD. A total
      of 629 hay samples from 86 farms were included in statistical analyses using
      linear multilevel regression models allowing to consider the nested structure of
      the data: individual-level (batch of hay) and group-level (farm). The outcome
      variable of these models was the concentration in hay (logarithmic value of
      concentration+1) of microorganisms incriminated in FLD (Absidia corymbifera,
      Eurotium spp., thermophilic actinomycetes). The simultaneous analysis of batch of
      hay- and farm-level factors showed that bad climatic conditions of harvest, high
      density hay-packing modes, (especially round bales) and altitude (2nd plateau,
      ]700-900] m) were the main factors associated with high concentrations of these
      microorganisms in hay. This study allowed clarification of the factors that
      influence the microbial concentration of hay with etiological agents of FLD.

PMID- 20047255
TI  - Occurrence of microscopic fungi and mycotoxins in conserved high moisture corn
      from Slovakia.
AB  - Contamination by microscopic fungi and mycotoxins in high moisture corn (HMC)
      silages conserved by chemical additives was investigated. The samples were
      examined for the concentration and identification of microscopic fungi able to
      grow on Malt and Czapek-Dox agar and for mycotoxins content (deoxynivalenol, T-2
      toxin, zearalenone and total aflatoxins, fumonisins, ochratoxins) by direct
      competitive enzyme-linked immunosorbent assays. The average fungal counts were
      3.37 +- 2.52 log cfu/g in control HMC silages, 2.91 +- 0.51 log cfu/g in HMC
      silages treated by organic salts and inorganic salt, 3.62 +- 1.46 log cfu/g in
      HMC ensiled with organic acids and 3.49 +- 1.12 log cfu/g of HMC silages treated
      by organic acids along with organic salt. In this study, 740 isolates belonging
      to 10 fungal species representing 9 genera were recovered. The genera of
      microscopic fungi most frequently found in HMC were Penicillium (56.49
      percentages) and Paecilomyces (32.16 percentages). T-2 toxin was the secondary
      metabolite with the highest concentration ranging from 179.13 +- 3.04 to 249.40 +
      24.69 micrograms/kg, followed by deoxynivalenol and total fumonisins. The
      highest mean of deoxynivalenol level was 0.13 +- 0.02 mg/kg and concentration of
      total fumonisins ranged from 20.13 +- 2.53 to 90.33 +- 10.35 micrograms/kg. This
      study indicated that application of chemical additives containing organic acids,
      organic salts and inorganic salt was sufficient to inhibit mycotoxins formation.
      The use of calcium formiate, sodium benzoate and sodium nitrite resulted in high
      hygienic quality of HMC silages and significantly reduced the concentration of
      zearalenone, deoxynivalenol and total ochratoxins and fumonisins.

PMID- 20047256
TI  - Swine confinement buildings: effects of airborne particles and settled dust on
      airway smooth muscles.
AB  - Swine confinement workers are exposed to various contaminants. These agents can
      cause airway inflammation and bronchoconstriction. This study was undertaken to
      evaluate if the bronchoconstrictive effects of swine barn air and settled dust
      are mediated by endotoxin, and if these effects are directly mediated on airway
      smooth muscles. Mouse tracheas where isolated and mounted isometrically in organ
      baths. Tracheas, with or without epithelium, were attached to a force transducer
      and tension was recorded. Concentrated swine building air at 68 EU/ml or settled
      dust extract at 0.01 g/ml were added for 20 minutes and tracheal smooth muscle
      contraction was measured. Direct role of LPS was assessed by removing it from air
      concentrates with an endotoxin affinity resin. Swine barn air and settled dust
      extract caused contraction of tracheal smooth muscle by 26 and 20%, respectively,
      of the maximal induced by methacholine. Removal of epithelium did not affect the
      contractile effects. LPS alone and LPS with peptidoglycans did not induce
      contraction. However, when endotoxin was removed from swine barn air
      concentrates, it lost 24% of its contractile effect. Concentrated swine barn air
      and settled dust have direct effects on airway smooth muscles. This effect is
      partially due to LPS but a synergy with other components of the environment of
      swine confinement buildings is required.

PMID- 20047257
TI  - Testing of human specimens for the presence of highly pathogenic zoonotic avian
      influenza virus A(H5N1) in Poland in 2006-2008 - justified or unnecessary steps?
AB  - Since 1997, human infections with highly pathogenic zoonotic avian influenza
      viruses have shown that the risk of influenza pandemic is significant. In Europe,
      infections caused by the highly pathogenic avian influenza A(H7N7) virus were
      confirmed in the human population in 2003 in the Netherlands. Moreover, outbreaks
      of A(H5N1) infections were observed in wild and farm birds in different European
      regions, including Poland in 2006-2008. This study presents 16 patients in Poland
      from whom clinical specimens were collected and tested for A(H5N1) highly
      pathogenic avian influenza. This article shows the results of laboratory tests
      and discusses the legitimacy of the collection and testing of the specimens. All
      patients were negative for A(H5N1) infection. Nevertheless, only two patients met
      clinical and epidemiological criteria from the avian influenza case definition.
      The conclusion is that there is still a strong necessity for increasing the
      awareness of medical and laboratory staff, as well as the awareness of some
      occupational groups about human infections with avian influenza viruses,
      including the importance of seasonal influenza vaccination. It should also be
      emphasized that in the case of patients suspected of being infected with avian
      influenza, the information about clinical symptoms is insufficient and must be
      accompanied by a wide epidemiological investigation.

PMID- 20047258
TI  - The concentration of volatile organic compounds (VOCs) in pig farm air.
AB  - The aim of the study was to assess the level of air pollution by volatile organic
      compounds (VOCs) in a pig fattening house and in its vicinity. Air samples for
      chromatographic analysis were taken in the fattening house and in the vicinity of
      the farm. The air quality study shows that the level of organic gaseous
      pollutants was twice as high in the fattening house as in the atmospheric air.
      Almost a half of the organic gaseous pollutants determined in the fattening house
      air are listed among the harmful chemical factors in the work environment.
      Comparison of the results of the atmospheric air samples taken from the vicinity
      of the farm with the valid standards also shows very high levels of air pollution
      in the vicinity of the farm. A mean concentration of the sum of mercaptans,
      phenol, xylene, 2-methyl-1-propanol, and toluene exceeded their basic values
      determined in the atmospheric air stated for the calendar year [18].

PMID- 20047259
TI  - Seroepidemiological study of Lyme borreliosis among forestry workers in southern
      Poland.
AB  - Forestry workers are a professional group particularly exposed to tick-borne
      infections; however, continuous monitoring of anti-Borrelia burgdorferi
      antibodies in this group enables faster diagnosis and more effective treatment
      for borreliosis. A group of 1,155 forestry workers from six forest inspectorates
      in southern Poland were examined with the immunoenzymatic method (ELISA test).
      The general level of anti-Borrelia burgdorferi antibodies was 12.8 % in IgM
      class, and 25 % in IgG class. Markedly more seropositive results were found in
      the group of fieldworkers (13.8 % - IgM and 25.0 % - IgG) than in office workers
      (10.0 % - IgM and 13.7 % - IgG). The highest proportions of infections both in
      IgM and IgG class (17.4 % and 34.8 %, respectively) were recorded in the group of
      persons over 50 years of age, the lowest - in the group of workers younger than
      30 (IgM - 13.0 %, IgG - 14.1%). Significant differences in the level of
      seropositive results in IgG class were related to the workers' gender - in women
      the percentage was 9.8 %, in men - 28.1 %. It was found that in the studied
      region of southern Poland, considered to be non-endemic, borreliosis occurs as a
      health risk to forestry workers.

PMID- 20047260
TI  - Incidence of fungals in a vineyard of the denomination of origin ribeiro (Ourense
      - north-western Spain).
AB  - Knowledge about the fungal spores most abundant in the atmosphere of a vineyard
      is of great use since it allows development of prediction models of the spore
      concentration, and therefore application of phytosanitary treatments only when
      high levels of fungal propaguls are detected. In this study the concentration of
      phytopathogenic spores is related with the different phenological stages of the
      vineyard, and a prediction model developed for each fungal type using
      meteorological, phenological and spore concentrations variables. The study was
      carried out in a vineyard of the Ribeiro district during the year 2007. For the
      aerobiological study a volumetric Hirst type trap was used, while phenological
      observations were carried out on 20 plants of the three varieties monitored
      (Treixadura, Godello and Loureira) following the phenological scale standardized
      by the BBCH. Botrytis reached the highest annual total value with 16,145 spores,
      followed by Plasmopara with 747 spores and Uncinula with 578 spores. In order to
      forecast the concentration of the phytopathogenic fungal spores, equations of
      lineal regression were elaborated including as estimators, variables with high
      correlation coefficient. For Botrytis the regression equation explained 42.4% of
      the variability of spore concentration, 26.1% for Uncinula and 24.7% for
      Plasmopara.

PMID- 20047261
TI  - What is the percentage of pathogenic borreliae in spirochaetal findings of
      mosquito larvae?
AB  - In this study, larvae (1,179 ex.) of mosquito genera Culex were examined for the
      presence of spirochaetes by Dark Field Microscopy (DFM) at the locality of
      Blansko (Czech Republic) in of 2004-2008. DFM spirochaete positive samples (25.4
      %) were investigated by nested PCR; only 4 samples were positive for the presence
      of Borrelia burgdorferi sensu lato, which is 0.3 % of the total examined samples.
      We can conclude that only a low percentage of pathogenic borreliae are presented
      in mosquito larvae, while the spirochaete of undefined genera infect larvae in
      high amounts.

PMID- 20047262
TI  - Factors involved in the phenological mechanism of Alnus flowering in Central
      Europe.
AB  - The objectives of this paper are to ascertain the main factors involved in the
      phenological mechanism of alder flowering in Central Europe by understanding the
      influence of the main meteorological parameters, the North Atlantic Oscillation
      (NAO) effect and the study of the Chill and Heat requirements to overcome
      dormancy. Airborne pollen (1995-2007) was collected in Poznan (Poland) by means a
      volumetric spore trap. Temperatures for February, and January and February
      averages of the NAO are generally key factors affecting the timing of the alder
      pollen seasons. Chilling accumulation (which started in Poznan at the beginning
      of November, while the end took place during the month of January) of 985 CH with
      a threshold temperature of -0.25 degrees C, followed by 118 GDD degrees C with a
      threshold temperature of 0.5 degrees C, were necessary to overcome dormancy and
      produce the onset of flowering. The calculated dormancy requirements, mean
      temperatures of the four decades of the year, and January and February average
      NAO index recorded during the period before flowering, were used to construct
      linear and multiple regression models in order to forecast the start date of the
      alder pollen seasons Its accuracy was tested using data from 2007, and the
      difference between the predicted and observed dates ranged from 3-7 days.

PMID- 20047263
TI  - Occurrence of IgG antibodies to Anaplasma phagocytophilum in humans suspected of
      Lyme borreliosis in eastern Slovakia.
AB  - Human granulocytic anaplasmosis (HGA) and Lyme borreliosis (LB) are tick-borne
      and emerging infectious diseases caused by the Anaplasma phagocytophilum and
      Borrelia burgdorferi species. In Europe, including Slovakia, the principal vector
      of both pathogens is the common tick - Ixodes ricinus, in which double infections
      with these pathogens have been reported. The aim of our study was evidence of IgG
      antibodies against A. phagocytophilum in blood sera of humans with suspects LB
      from several Clinics of University Hospitals, and the evaluation of the
      possibility of B. burgdorferi and A. phagocytophilum co-infection in examined
      patients. The serological method ELISA was used to detect IgM and IgG antibodies
      against B. burgdorferi. Anti-A. phagocytophilum IgG antibodies were analyzed by
      the A. phagocytophilum Indirect Immunofluorescence Antibody (IFA) IgG test. A
      total of 214 human samples (91 men, 123 women) were obtained from patients living
      in Kosice town and in villages around Kosice (Eastern Slovakia). IgG antibodies
      against A. phagocytophilum were detected in 15 cases (6 men, 9 women), which
      represented 7.0 % positivity. Two cases of the co-infection B. burgdorferi with
      A. phagocytophilum, which equals 0.93 % of the total number, were found.

PMID- 20047264
TI  - Cathelicidin LL-37, granzymes, TGF-beta1 and cytokines levels in induced sputum
      from farmers with and without COPD.
AB  - The cathelicidin LL-37 is an antimicrobial and lipopolysaccharide neutralizing
      peptide, possessing pro-inflammatory, tissue repair and remodeling activities.
      Recent reports indicate that the progression of COPD might be connected with
      increased levels of LL-37. The numerous experimental data show the potential role
      of LL-37 in the response to the exposure to organic dust (containing
      lipopolysaccharide and microorganisms) which is one of the major COPD causative
      factors. This work strives to further prove the role of LL-37 in the development
      of COPD. A cross-sectional study was conducted in 30 farmers in the early stages
      of COPD according to GOLD, 36 healthy farmers and 16 healthy urban dwellers.
      Collection of induced-sputum samples and lung function testing were conducted
      before and after work. The quantification of the LL-37 in sputum samples was
      performed by mass spectrometry and radioisotope techniques. Levels of granzymes A
      and B, IL-8, IFN-gamma and TGF-beta1 in sputum were measured by ELISA technique.
      Statistical analysis was conducted by Kruskal-Wallis and Mann-Whitney U tests.
      Significantly higher levels of LL-37 were observed in sputum samples from farmers
      with COPD compared to healthy individuals. The concentration of LL-37 in sputum
      from farmers was significantly higher compared to urban dwellers. The same was
      true for both granzymes A and B. The results of this study suggest that LL-37 and
      granzymes A and B may add to the development of COPD. The results suggest also
      their role in an organism's response to organic dust exposure.

PMID- 20047265
TI  - Anaplasma phagocytophilum infection of red foxes (Vulpes vulpes).
AB  - The investigation of Anaplasma phagocytophilum infection covered 111 red foxes
      from the Mazovian Province. Determination was based on PCR amplification of 16S
      rRNA gene and the portion of msp4 gene coding MSP4 major surface protein. The
      presence of A. phagocytophilum was found in 2.7 % of foxes.

PMID- 20047266
TI  - Influence of hyperosmotic conditions on basophil CD203c upregulation in patients
      with food-dependent exercise-induced anaphylaxis.
AB  - Increased in vitro basophil activation in buffers of slightly elevated osmolarity
      in 2 cases of food-dependent exercise-induced anaphylaxis is presented. These
      data may suggest the importance of basophil activation degree in pathogenesis of
      this life threatening syndrome.

PMID- 20047267
TI  - Drinking of chokeberry juice from the ecological farm Dzieciolowo and
      distensibility of brachial artery in men with mild hypercholesterolemia.
AB  - The aim of the study was to estimate the influence of drinking chokeberry juice
      on the endothelial function in men with mild hypercholesterolemia. It was shown
      that chronic treatment with flavonoids improves vascular function and reduces
      cardiovascular remodelling by increasing NO release from endothelial cells. A
      group of 35 men diagnosed with mild hypercholesterolemia (mean age: 53.9 +-5.8
      years), with no earlier pharmacological treatment, were enrolled to the study. In
      all men, assessment of endothelial function, and serum lipids level were carried
      out at four time points: at the beginning of the studies, after 6 weeks of
      regular drinking of chokeberry juice, after 6 weeks without drinking the juice,
      then after repeated 6 weeks of drinking chokeberry juice. During the study,
      significant decreases in serum total cholesterol, LDL cholesterol and
      triglycerides levels were observed. A statistically significant increase in serum
      nitric oxide (NO) concentration and in the flow mediated dilatation (FMD) were
      observed. At the beginning, FMD > or = 7 % was present in 13 of 35 subjects (37.1
      %). After 6 weeks of regular chokeberry juice drinking, FMD > or = 7 % was
      present in 29 of 35 subjects (82.9 %). However, after 6 weeks abstaining from
      drinking the juice and repeated exposure to 6 weeks drinking of chokeberry juice,
      FMD > or = 7 % was present in all studied subjects. Regular drinking of
      chokeberry juice has a beneficial effect on endothelial function and lipid
      metabolism in men with mild hypercholesterolemia.

PMID- 20047268
TI  - Maternal passive smoking during pregnancy and neonatal health.
AB  - The objective of the study was the evaluation of effect of passive smoking among
      pregnant women on the health condition of their newborn babies. The study covered
      150 healthy, non-smoking women from the Lublin Region. Among the total number of
      respondents, 45.34 % were not exposed during pregnancy to passive smoking at
      their workplace, while 13.33 % were passive smokers throughout the whole period
      of pregnancy. The state of their babies was assessed according to the APGAR
      Scale. A statistically significant correlation was noted between the maternal
      exposure to passive smoking during pregnancy and evaluation of the babies
      according to the APGAR Scale. No statistically significant relationship was noted
      between the date of delivery, the birth weight of babies, the onset of lactation,
      the problems with breastfeeding and maternal passive smoking during pregnancy.

PMID- 20047269
TI  - The occurrence of Toxoplasma gondii and Borrelia burgdorferi sensu lato in Ixodes
      ricinus ticks from east Poland with the use of pcr.
AB  - 715 Ixodes ricinus ticks from 4 regions of Lublin macroregion (Piotrowice,
      Polesie National Park, Dabrowa and Leczynsko-Wlodawskie Lakeland) were examined
      for the presence of Borrelia burgdorferi sensu lato and Toxoplasma gondi, using
      polymerase chain reaction (PCR) and nested-PCR methods. The clonal type of
      samples tested positive for T. gondii was identified by amplification and
      fragmenting with restrictions enzymes (RFLP-restriction fragment length
      polymorphism). Positive results were confirmed by sequencing. The overall
      percentage of tick infection with B. burgdorferi sensu lato (s.l.) was 12.7 %,
      and with T. gondii - 12.6 %. The coincidence of both pathogens was found in 2.4 %
      of the examined specimens. The highest proportions of infections were detected in
      females, among all the developmental stages, both in the case of single pathogens
      (23.5 % of ticks infected with B. burgdorferi s.l., and 19.7% - with T. gondii),
      and their coincidence (3.8 % of all the tested females). RFLP PCR test detected
      that type I and atypical (type A) T. gondii strains were most common in ticks.
      The presence of type II/III was confirmed exclusively in females.

PMID- 20047270
TI  - Fungi on wheat bran and their toxinogenity.
AB  - To survey the overall fungal contamination and toxicological potential of
      isolated fungi, a mycological investigation of 56 samples of wheat bran was
      carried out during March-June 2004 in Slovakia. Despite of low values of water
      activity found in the samples reaching an average of 0.54, the individual samples
      were contaminated with fungi in a range from 1.82 x 10(1) - 3.42 x 10(4) colonies
      forming units per gram of sample (CFU/g). A total number of 65 fungal species
      pertaining to 23 genera were recovered. The most dominant and diverse genus was
      Penicillium (20 spp.) followed by Aspergillus (10 spp.) and Cladosporium (3 spp.)
      with 100 percentages, 89 percentages and 72 percentages frequency, respectively.
      Isolates of potentially toxinogenic species recovered from the samples were found
      to produce various mycotoxins, namely citrinin (23 isolates), cyclopiazonic acid
      (43 isolates), griseofulvin (23 isolates), ochratoxin A (14 isolates), patulin
      (30 isolates), penitrem A (18 isolates) and sterigmatocystin (7 isolates).
      Furthermore, fumonisin B1 as well as moniliformin producing Fusarium strains,
      were recovered. It is evident that this type of cereal commodity is a significant
      source of toxicologically relevant species of which majority are true
      toxinogenic.

PMID- 20047271
TI  - Vertically aligned boron nitride nanosheets: chemical vapor synthesis,
      ultraviolet light emission, and superhydrophobicity.
AB  - Boron nitride (BN) is a promising semiconductor with a wide band gap (
      approximately 6 eV). Here, we report the synthesis of vertically aligned BN
      nanosheets (BNNSs) on silicon substrates by microwave plasma chemical vapor
      deposition from a gas mixture of BF(3)-N(2)-H(2). The size, shape, thickness,
      density, and alignment of the BNNSs were well-controlled by appropriately
      changing the growth conditions. With changing the gas flow rates of BF(3) and
      H(2) as well as their ratio, the BNNSs evolve from three-dimensional with
      branches to two-dimensional with smooth surface and their thickness changes from
      20 to below 5 nm. The growth of the BNNSs rather than uniform granular films is
      attributed to the particular chemical properties of the gas system, mainly the
      strong etching effect of fluorine. The alignment of the BNNSs is possibly induced
      by the electrical field generated in plasma sheath. Strong UV light emission with
      a broad band ranging from 200 to 400 nm and superhydrophobicity with contact
      angles over 150 degrees were obtained for the vertically aligned BNNSs. The
      present BNNSs possess the properties complementary to carbon nanosheets such as
      intrinsically semiconducting, high temperature stability, and high chemical
      inertness and may find applications in ultraviolet nanoelectronics, catalyst
      supports, electron field emission, and self-cleaning coatings, etc., especially
      those working at high temperature and in harsh environments.

PMID- 20047272
TI  - Inhibition of xanthine oxidase by Acacia confusa extracts and their
      phytochemicals.
AB  - Acacia confusa Merr. (Leguminosae) is traditionally used as a medicinal plant in
      Taiwan. In the present study, the XOD-inhibitory activity of ethanolic extracts
      from A. confusa was investigated for the first time. Results demonstrated that
      the ethanolic extract of A. confusa heartwood had a strong XOD-inhibitory
      activity. Among all fractions derived from heartwood extracts, the EtOAc fraction
      exhibited the best inhibitory activity. Following column chromatography and
      reverse-phase high-performance liquid chromatography, eight specific
      phytochemicals including melanoxetin, 7,8,3',4'-tetrahydroxyflavone, transilitin,
      okanin, 3,7,8,3'-tetrahydroxy-4'-methoxyflavone, 7,8,3'-trihydroxy-3,4'
      dimethoxyflavone, 7,3',4'-trihydroxyflavone, and 7,3',4'-trihydroxy-3
      methoxyflavone were isolated and identified from the EtOAc fraction. In addition,
      the IC(50) values indicated that okanin showed the strongest XOD-inhibitory
      effect (IC(50) value of 0.076 microM), followed by melanoxetin (0.274 microM) and
      allopurinol (4.784 microM). The present study revealed that okanin and
      melanoxetin showed excellent inhibition on XOD in noncompetitive and competitive
      mode, respectively, and their inhibitory activity is better than that of
      allopurinol. This is the first study that demonstrates the XOD-inhibitory
      performance of okanin and melanoxetin.

PMID- 20047273
TI  - Characterization of adsorption and degradation of diuron in carbonatic and
      noncarbonatic soils.
AB  - The adsorption and degradation of the pesticide diuron in carbonatic and
      noncarbonatic soils were investigated to better understand the fate and transport
      of diuron in the environment. Batch adsorption experiments yielded isotherms that
      were well-described by the linear model. Adsorption coefficients normalized to
      soil organic carbon content (K(oc)) were lowest for carbonatic soils, averaging
      259 +/- 48 (95% CI), 558 +/- 109, 973 +/- 156, and 2090 +/- 1054 for carbonatic
      soils, Histosols, Oxisols, and Spodosols, respectively. In addition, marl
      carbonatic soils had much lower K(oc) values (197 +/- 27) than nonmarl-carbonatic
      soils. Diuron degradation data fit a first-order reaction kinetics model,
      yielding half-lives in soils ranging from 40 to 267 days. There was no
      significant difference between the average diuron degradation rate coefficients
      of each of the soil groups studied. Given the low adsorption capacity of
      carbonatic soils, it may be advisable to lower herbicide application rates in
      agricultural regions with carbonatic soils such as southern Florida to protect
      aquatic ecosystems and water quality.

PMID- 20047274
TI  - Orientational microdynamics and magnetic-field-induced ordering of clay platelets
      detected by 2H NMR spectroscopy.
AB  - The orientation of montmorillonite clays induced by a static magnetic field is
      quantified by using (2)H NMR spectroscopy. Indeed, the residual quadrupolar
      splitting of the (2)H resonance line measured for heavy water is a direct
      consequence of the specific orientation of the clay platelets in the static
      magnetic field. In the dilute regime, this residual splitting increases linearly
      with clay concentration, which confirms that the clay/clay electrostatic
      repulsions remain negligible by comparison with the diamagnetic coupling of these
      anisotropic platelets. At higher concentration, the electrostatic repulsion
      between clay particles markedly enhances the detected splitting. Such enhancement
      is well predicted by numerical simulations. By varying the size of the clay
      platelets and the strength of the static magnetic field, it is possible to
      evaluate the order of magnitude of the diamagnetic susceptibility of these
      anisotropic colloids.

PMID- 20047275
TI  - Applications of direct analysis in real time-mass spectrometry (DART-MS) in
      Allium chemistry. (Z)-butanethial S-oxide and 1-butenyl thiosulfinates and their
      S-(E)-1-butenylcysteine S-oxide precursor from Allium siculum.
AB  - Lachrymatory (Z)-butanethial S-oxide along with several 1-butenyl thiosulfinates
      was detected by DART mass spectrometry upon cutting Allium siculum , a popular
      ornamental Allium species used in some cultures as a spice. (Z)-Butanethial S
      oxide isolated from the plant was shown to be identical to a synthetic sample.
      Its likely precursor, (R(S),R(C),E)-S-(1-butenyl)cysteine S-oxide
      (homoisoalliin), was isolated from homogenates of A. siculum, and a closely
      related species Allium tripedale , and fully characterized. Through use of LC-MS,
      a series of related gamma-glutamyl derivatives were tentatively identified in A.
      siculum and A. tripedale homogenates, including gamma-glutamyl-(E)-S-(1
      butenyl)cysteine and its S-oxide, gamma-glutamyl-S-butylcysteine and its S-oxide,
      and gamma-glutamyl-S-methylcysteine and its S-oxide. Because compounds containing
      the 1-butenyl group have not been previously identified in genus Allium species,
      this work extends the range of known Allium sulfur compounds. The general
      applicability of DART mass spectrometry in identifying naturally occurring,
      thermally fragile thial S-oxides and thiosulfinates is illustrated with onion,
      Allium cepa , as well as a plant from a different genus, Petiveria alliacea .

PMID- 20047276
TI  - Antitrypanosomal activity of 1,2-dihydroquinolin-6-ols and their ester
      derivatives.
AB  - The current chemotherapy for second stage human African trypanosomiasis is
      unsatisfactory. A synthetic optimization study based on the lead antitrypanosomal
      compound 1,2-dihydro-2,2,4-trimethylquinolin-6-yl 3,5-dimethoxybenzoate
      (TDR20364, 1a) was undertaken in an attempt to discover new trypanocides with
      potent in vivo activity. While 6-ether derivatives were less active than the lead
      compound, several N1-substituted derivatives displayed nanomolar IC(50) values
      against T. b. rhodesiense STIB900 in vitro, with selectivity indexes up to
      >18000. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate (10a) displayed
      an IC(50) value of 0.014 microM against these parasites and a selectivity index
      of 1700. Intraperitoneal administration of 10a at 50 (mg/kg)/day for 4 days
      caused a promising prolongation of lifespan in T. b. brucei STIB795-infected mice
      (>14 days vs 7.75 days for untreated controls). Reactive oxygen species were
      produced when T. b. brucei were exposed to 10a in vitro, implicating oxidative
      stress in the trypanocidal mode of action of these 1,2-dihydroquinoline
      derivatives.

PMID- 20047277
TI  - 2,4,6-trisubstituted triazines as protein a mimetics for the treatment of
      autoimmune diseases.
AB  - A first-in-class series of low molecular weight trisubstituted triazines were
      synthesized and evaluated for their ability to mimic protein A binding to human
      IgG antibody. The structure-activity relationship (SAR) demonstrates that the 1,3
      phenylenediamine component was essential for robust activity. Twenty-two
      compounds, represented by lead molecule 34, displayed significant activity
      compared to protein A. These compounds may prove useful for the treatment of
      autoimmune disease.

PMID- 20047278
TI  - Comparison of homogeneous single-label fluorometric binding assays: fluorescence
      polarization and dual-parametric quenching resonance energy transfer technique.
AB  - The time-resolved fluorescence technique, quenching resonance energy transfer,
      QRET, relies on a single-labeled binding partner in combination with a soluble
      quencher. The quencher reduces efficiently the fluorescence of the unbound
      labeled ligand, whereas the fluorescence of the bound fraction is detectable.
      This approach allows the development of homogeneous screening assays in a simple
      and cost-effective manner. In this study, two single-label fluorometric methods,
      fluorescence polarization (FP) and the QRET technique, are compared in a simple
      biochemical model immunoassay of estradiol. Estradiol-6-amino was labeled with
      fluorescein and lanthanide(III) chelates for the FP and QRET assays,
      respectively. The labeled estradiols were allowed to compete against free
      estradiol, and the assay parameters were investigated. The EC(50) value of QRET
      assay using europium(III)-labeled estradiol was 0.1 nM, and the assay sensitivity
      was approximately 10 pM. These values were more than 10-fold lower than those for
      the FP assay with Z' values higher than 0.75 for both assays. The high
      sensitivity was attributed to a low concentration of antibody fragment and
      labeled estradiol used in the QRET assay. This reduces cost in screening studies
      without sacrificing the assay performance. A signal-to-background ratio (S/B) of
      more than 20 was reached in the QRET assay at elevated concentration of the assay
      components, whereas S/B of 3.6 was measured in the FP assay when both assays
      shared the same EC(50) value of 1 nM. Multiplexing of assays is a cost-effective
      means to run screening studies as multiple data can be extracted from a single
      experiment. Therefore, multiplexing of the QRET assay was investigated and its
      feasibility was successfully demonstrated in a dual-parametric assay using
      estradiol labeled with europium(III) and terbium(III) chelates.

PMID- 20047279
TI  - Two-step in vitro antibody affinity maturation enables estradiol-17beta assays
      with more than 10-fold higher sensitivity.
AB  - Immunoassays for haptens depend on competitive hapten-anti-hapten reactions, and
      consequently their sensitivities are significantly influenced by the affinities
      of anti-hapten antibodies. Thus, genetically engineered antibodies, which have
      much higher affinities than native antibodies, should increase assay
      sensitivities. Here, we created a mutated single-chain Fv fragment (scFv) against
      estradiol-17beta (E(2)) that allowed immunoassays with a much improved
      sensitivity. Two steps of affinity maturation were performed on a "wild-type"
      scFv (scFv#E4-4) composed of V(H) and V(L) domains from a mouse anti-E(2)
      antibody (Ab#E4-4). First, we conducted complementarity-determining region (CDR)
      targeted mutagenesis by "CDR-shuffling". Gene fragments encoding CDRs H2, H3, L1,
      and L3, each of which contained random point mutations, were combined by
      "shuffling" into the gene encoding the scFv#E4-4 scaffold. After phage display
      and repeated panning, we isolated a mutated scFv clone [scFv#m1-e7; Ile(L29)Val]
      that had 5-fold higher affinity (K(a) = 2.6 x 10(8) M(-1)) compared to the Ab#E4
      4 Fab fragment (Fab#E4-4). Next, the entire V(H) and V(L) of this clone were
      randomly mutated by error-prone polymerase chain reaction (PCR). From this
      library, we found an improved clone, scFv#m2-c4 (K(a) = 6.3 x 10(8) M(-1);
      Lys(H19)Arg, Tyr(H56)Phe, Ser(H84)Pro, Glu(H85)Gly, Gln(L27)Arg, Leu(L36)Met,
      Ser(L63)Gly, and Ser(L77)Gly). ScFv#m2-c4 had more than 10-fold higher
      sensitivity (the midpoint of its dose-response curve was 0.56 ng) than Fab#E4-4
      (midpoint 9.0 ng/assay) in a competitive E(2) radioimmunoassay, and even higher
      sensitivity [midpoint 21 pg/assay, and a limit of detection of 0.47 pg (1.7
      fmol)/assay] in a competitive enzyme-linked immunosorbent assay. Cross-reactivity
      with selected E(2)-related endogenous steroids strongly suggested that scFv#m2-c4
      has improved specificity compared to conventional antibodies.

PMID- 20047280
TI  - Novel synthesis of the hexahydroimidazo[1,5b]isoquinoline scaffold: application
      to the synthesis of glucocorticoid receptor modulators.
AB  - The first stereoselective synthesis of the hexahydroimidazo[1,5b]isoquinoline
      (HHII) scaffold as a surrogate for the steroidal A-B ring system is described.
      The structure-activity relationships of the analogs derived from this scaffold
      show that the basic imidazole moiety is tolerated by the glucocorticoid receptor
      (GR) in terms of binding affinity, although the partial agonist activity in the
      transrepressive assays depends on the substitution pattern on the B-ring. More
      importantly, most compounds in the HHII series bearing a tertiary alcohol moiety
      on the B-ring are either inactive or significantly less active in inducing GR
      mediated transactivation, thus displaying a "dissociated" pharmacology in vitro.

PMID- 20047281
TI  - Electrochemical surface plasmon resonance: basic formalism and experimental
      validation.
AB  - A quantitative formalism of electrochemical surface plasmon resonance (EC-SPR)
      was developed for studying electrochemical reactions. The EC-SPR signal from the
      reactions was found to be a convolution function of electrochemical current, and
      therefore, EC-SPR is a powerful tool that can provide information similar to the
      conventional current-based electrochemical techniques. As an example, potential
      sweep EC-SPR was analyzed in details and was found to provide a new way to
      measure convolution voltammetry without the need of numerical integration. In
      addition to the benefits provided by the conventional convolution voltammetry,
      the EC-SPR has several unique advantages, including (1) spatial resolution that
      is particularly attractive for studying heterogeneous reactions, (2) optical
      properties of the reactions species that may assist identification of reaction
      mechanisms, and (3) high surface sensitivity for studying surface binding of the
      reaction species. Experiments and numerical simulations were carried out for a
      model system, hexaammineruthenium(III) chloride. The simultaneously measured
      electrochemical current and SPR response confirmed the relationship between the
      two quantities, and the numerical simulations were in excellent agreement with
      the measurements.

PMID- 20047282
TI  - Nickel-catalyzed reductive cross-coupling of aryl halides with alkyl halides.
AB  - The direct reductive cross-coupling of alkyl halides with aryl halides is
      described. The transformation is efficient (equimolar amounts of the starting
      materials are used), generally high-yielding (all but one between 55 and 88%
      yield), highly functional-group-tolerant [OH, NHBoc, NHCbz, Bpin, C(O)Me,
      CO(2)Et, and CN are all tolerated], and easy to perform (uses only benchtop
      stable reagents, tolerates small amounts of water and oxygen, changes color when
      complete, and uses filtration workup). The reaction appears to avoid the
      formation of intermediate organomanganese species, and a synergistic effect was
      found when a mixture of two ligands was employed.

PMID- 20047283
TI  - Construction of all-carbon quaternary center by R2AlCl-mediated ring-opening
      reaction of oxacycles.
AB  - An unexpected R(2)AlCl-mediated ring-opening reaction of oxacycles for the
      formation of all-carbon quaternary centers was discovered, and a possible
      mechanism is proposed. The developed chemistry provides a concise approach to
      synthesize structural diverse of dolastane-type compounds.

PMID- 20047284
TI  - Shock wave study of the thermal decomposition of CF3 and CF2 radicals.
AB  - The thermal dissociation reactions CF(3) + M --> CF(2) + F + M (reaction 1 ) and
      CF(2) + M --> CF + F + M (reaction 3 ) were studied behind shock waves. CF(2)
      radicals were monitored through their UV absorption. By working at very low
      reactant concentrations, the rate coefficients of the unimolecular processes
      could be derived. Reaction 1 was investigated between 1600 and 2300 K in the
      intermediate range of the falloff curves, at approximately 10 times larger bath
      gas pressures than employed in earlier work (Srinivasan, N. K.; Su, M.-C.;
      Michael, J. V.; Jasper, A. W.; Klippenstein, S. J.; Harding, L. B. J. Phys. Chem.
      A 2008, 112, 31). The combination of the two sets of data, together with
      theoretical modeling, allows one to construct falloff curves and to provide
      complete representations of the temperature and pressure dependences of the rate
      coefficients. Reaction 3 was studied in the limiting low-pressure range and, over
      the range 2900-3800 K, a rate coefficient k(3) = [Ar] 1.6 x 10(15) exp(-48,040
      K/T) cm(3) molecule(-1) s(-1) was obtained. Representations of the rate
      coefficients over the full falloff curves were again derived by theoretical
      modeling.

PMID- 20047285
TI  - Band shape heterogeneity of the low-energy chlorophylls of CP29: absence of mixed
      binding sites and excitonic interactions.
AB  - A number of spectroscopic characteristics of three almost isoenergetic, red
      shifted chlorophylls (chls) in the PS II antenna complex CP29 are investigated
      with the aim of (i) determining whether their band shapes are substantially
      identical or not, (ii) addressing the topical problem of whether they are
      involved in excitonic interactions with other chls, and (iii) establishing
      whether their binding sites may be defined as "mixed" with respect to their
      capacity to bind chls a and b. The three chls A2-CHL612, A3-CHL613, and B3-CHL614
      were analyzed after in vitro apoprotein-pigment reconstitution using the CP29
      coding sequence from Arabidopsis thaliana for both the wild-type and mutant
      complexes. Difference spectra thermal broadening analyses indicated that the half
      bandwidths varied between 12 and 15 nm (at room temperature), due mainly to
      differences in the optical reorganization energy (25-40 cm(-1)). Moreover, only
      the A2 chl displayed an intense vibrational band in the 300-600 cm(-1) interval
      from the 0-0 transition. We conclude that within the red absorbing (approximately
      680 nm) antenna chls of a single chl-protein complex a marked spectral band shape
      heterogeneity exists. By analysis of the absorption and circular dichroism
      spectra no evidence was found of significantly strong excitonic interactions. The
      single gene mutation of the A3 and B3 binding sites causes absorption changes in
      both the long wavelength chl a absorbing region and in the chl b spectral region.
      This has previously been observed and was attributed to "mixed" chl a/b binding
      sites [Bassi, R., Croce, R., Cugini, D., and Sandona, D. (1999) Proc. Natl. Acad.
      Sci. U.S.A. 96,10056-10061]. This interpretation, while in principle not being
      unreasonable, is shown to be incorrect for these two chls.

PMID- 20047286
TI  - Effect of hydrophobicity on the interaction between antimicrobial peptides and
      poly(acrylic acid) microgels.
AB  - The influence of peptide hydrophobicity on the interaction between antimicrobial
      peptides and poly(acrylic acid) microgels was studied by end-tagging the
      kininogen-derived antimicrobial peptide GKHKNKGKKNGKHNGWK (GKH17) and its
      truncated variant KNKGKKNGKH (KNK10) with oligotryptophan groups of different
      lengths. Microgel deswelling and reswelling in response to peptide binding and
      release was studied by micromanipulator-assisted light- and fluorescence
      microscopy, peptide uptake in microgels was determined from solution depletion
      measurements, and peptide oligomerization was monitored by fluorescence
      spectroscopy. Results showed that oligomerization/aggregation of the
      hydrophobically end-tagged peptides is either absent or characterized by exposure
      of the tryptophan residues to the aqueous ambient, the latter suggesting small
      aggregation numbers. In addition, peptide uptake and affinity to the poly(acrylic
      acid) microgels increase with the number of tryptophan residues in the
      hydrophobic end tag, whereas peptide-induced microgel deswelling kinetics did not
      display this tag-length dependence to the same extent. Instead, long end tags
      resulted in anomalous shell formation, opposing further peptide-induced network
      deswelling. Theoretical modeling suggested that the deswelling kinetics in
      response to peptide binding is largely controlled by stagnant layer diffusion,
      but also that for peptides with sufficiently long hydrophobic tags, the shell
      constitutes an additional diffusion barrier, thus resulting in slower microgel
      deswelling. In addition, GKH17 and KNK10 peptides lacking the tryptophan end tags
      were substantially released on reducing peptide-microgel electrostatic
      interactions through addition of salt, an effect more pronounced for the shorter
      KNK10 peptide, whereas the hydrophobically end-tagged peptides remained bound to
      the microgels also at high ionic strength.

PMID- 20047287
TI  - Salt effect on the aggregation behavior of 1-decyl-3-methylimidazolium bromide in
      aqueous solutions.
AB  - Understanding of the specific salt effect on the aggregation behavior of ionic
      liquids (ILs) is relevant to multiple applications. In this work, the influence
      of a series of 15 salts on the aggregation behavior of [C(10)mim]Br in aqueous
      solutions has been investigated by conductivity, fluorescence, and dynamic light
      scattering. It was shown that NaCl, NaBr, NaI, CH(3)CO(2)Na, NaSCN, NaNO(3),
      NaBrO(3), NaClO(3), C(6)H(5)COONa, Na(2)CO(3), Na(2)SO(4), Na(2)C(4)H(4)O(6), and
      Na(3)CH(5)O(7) have salting-out effect, whereas FeBr(3) and AlBr(3) have salting
      in effect on the aggregation of [C(10)mim]Br in aqueous solutions. The effect of
      anions of the added sodium salts on the critical aggregation concentration (CAC),
      degree of anionic binding (beta), and aggregation number (N(agg)) of the IL
      basically follows the Hofmeister series, and the CAC values decrease but the beta
      and N(agg) values increase with increasing concentration of the salts.
      Hydrophobicity of the anions is suggested to play important roles in the salt
      effect on the aggregation of [C(10)mim]Br in aqueous solutions. Furthermore, the
      IL aggregates were found to grow slowly as the increase of the salt
      concentrations under studied static conditions, and resulting in the increased
      aggregation number of the IL. These results are expected to be useful in the
      applications of ionic liquids.

PMID- 20047288
TI  - Subdiffusive molecular motion in nanochannels observed by fluorescence
      correlation spectroscopy.
AB  - The influence of confinement on biomolecule motion in glass channels of
      nanometric height has been investigated with fluorescence correlation
      spectroscopy (FCS). We measured intrachannel molecule diffusion time and
      concentration based on a single-component diffusion model as a function of
      molecule size to channel height (r(g)/h). Poly(ethylene glycol) (PEG) of 20 kDa
      and dextran of 40 kDa showed a reduction of their diffusion coefficients of
      almost 1 order of magnitude when nanochannel height approached probe diameter,
      whereas rhodamine 6G (Rh6G) was shown to be almost unaffected from confinement.
      Subdiffusive motion has been proven for flexible molecules in nanochannels, and
      deviations toward a square root dependence of mobility with time for confinement
      up to molecule size r(g)/h approximately 0.5 were registered. Diffusion
      coefficient time dependence has been evaluated and described with a model that
      accounts for diffusion time increase due to molecule rearrangements related to
      molecule flexibility and surface interactions dynamics. The evaluation of the
      subdiffusive mode and the key parameters extracted at the single-molecule level
      of partitioning, intrachannel diffusion time, desorption time, and binding
      probability at surfaces can be exploited for the engineering of bioanalytic
      nanodevices.

PMID- 20047289
TI  - Glucocorticoid receptor phosphorylation modulates transcription efficacy through
      GRIP-1 recruitment.
AB  - The role of GR phosphorylation in modulating GR-mediated transcription is not
      fully understood. Here we show that the hGR is rapidly phosphorylated at S211 and
      S226 in response to the synthetic agonist dexamethasone (dex) in COS-1 cells.
      Using a triple phosphorylation mutant hGR construct, we demonstrate that
      phosphorylation at one or more S residues (from S203, S211, and S226) is required
      for maximal hGR-mediated transcriptional activation on the MMTV promoter in
      response to dex in COS-1 cells, but that this effect is promoter selective.
      Phosphorylation at these residues does not affect unliganded or agonist-induced
      hGR degradation, suggesting that the mechanism whereby hGR phosphorylation at
      these residues regulates GR-mediated transactivation via a GRE does not involve
      changes in GR half-life. We have previously shown a direct correlation between
      efficacy for transactivation and interaction of the hGR with glucocorticoid
      receptor interacting protein-1 (GRIP-1). Here we show by pull-down assays in the
      absence and presence of glucocorticoid response elements (GREs) that
      phosphorylation of the hGR is required for GR-GRIP-1 interaction. Chromatin
      immunoprecipitation (ChIP) assays revealed that hGR phosphorylation at one or
      more S residues (from S226, S211, and S203) is required for the recruitment of
      GRIP-1 to the synthetic MMTV promoter as well as to the endogenous GRE-containing
      glucocorticoid-induced leucine zipper (GILZ) promoter in intact COS-1 cells, but
      not for nuclear localization. Our results support the conclusion that
      phosphorylation at S203, S211, and/or S226 of the hGR is required for a maximal
      transcriptional response via the synthetic MMTV and endogenous GILZ GREs in COS-1
      cells, to enable recruitment of GRIP-1 to the hGR.

PMID- 20047290
TI  - Unprecedented marriage of a cationic pentanuclear cluster and a 2D polymeric
      anionic layer based on a flexible tripodal ligand and a Cu(II) ion.
AB  - The anionic CdI(2)-type topological net, [Cu(2)(tci)(2)](2-), and the
      pentanuclear copper cluster cation [Cu(5)(tci)(2)(OH)(2)(H(2)O)(8)](2+) [tci =
      tris(2-carboxyethyl)isocyanurate] form a complementary 3D supramolecular
      framework. Interestingly, there exist centrosymmetric cyclic (H(2)O)(18) clusters
      in the cavities.

PMID- 20047292
TI  - Tautomeric equilibrium of uracil and thymine in model protein-nucleic acid
      contacts. Spectroscopic and quantum chemical approach.
AB  - This work deals with tautomeric transformations of uracil (Ura) and thymine (Thy)
      in their model complexes with the deprotonated carboxylic group. Essential
      changes in the UV spectra of the bases upon their interaction with NaAc,
      vanishing signals of both imino protons in (1)H NMR spectra, and a perceptible
      decrease in intensity of both IR bands, related to the stretching vibrations
      nu(C=O) of the carbonyl groups, imply involvement of enolic tautomers. Results of
      quantum chemical calculations of the double complexes of the Ura(Thy) tautomers
      with CH(3)COO(-) at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory
      proved to be incompatible with the spectral features: despite the fact that the
      complexes of the enolic tautomers are much closer in energy to the diketo ones as
      compared to isolated tautomers, the energy gap between them is such that in
      tautomeric equilibrium dominate diketo forms. Calculations of triple complexes of
      the type CH(3)COO(-):Ura(Thy) tautomer:Na(+), taking into account the effect of
      the Na(+) coordination with tautomers, show that three triple complexes formed by
      enolic tautomers appeared more stable than those formed by diketo ones. This
      makes the UV and (1)H NMR data understandable, but the high residual intensity of
      the nu(C=O) bands in the IR spectra remains unclear. At that ion, Na(+) itself
      was not able to disturb the tautomeric equilibrium in the coordination complexes
      of the type Ura(Thy) tautomer:Na(+). To evaluate the DMSO effect, the CPCM
      solvation model was applied to triple complexes of the Ura tautomers. It appeared
      that in the solution there is coexistence between the diketo and enolic tautomers
      in a ratio of 53%:47%. This makes possible reconciliation of our experimental
      data. The biological significance of high-energy tautomers of nucleotide bases is
      discussed.

PMID- 20047293
TI  - FerriCast: a macrocyclic photocage for Fe3+.
AB  - The non-siderophoric Fe(3+) photocage FerriCast (4,5-dimethoxy-2-nitrophenyl)-[4
      (1-oxa-4,10-dithia-7-aza-cyclododec-7-yl)phenyl] methanol (2) has been prepared
      in high yield using an optimized two-step reaction sequence that utilizes a
      trimethylsilyl trifluoromethanesulfonate (TMSOTf) assisted electrophilic aromatic
      substitution as the key synthetic step. Spectrophotometric assessment of Fe(3+)
      binding to FerriCast revealed a binding stoichiometry and metal ion affinity
      dependent on the nature of the counterion. Exposure of FerriCast to 350 nm light
      initiates a photoreaction that converts FerriCast into FerriUnc (4,5-dimethoxy-2
      nitrosophenyl)-[4-(1-oxa-4,10-dithia-7-aza-cyclododec-7-yl)phenyl]-methanone),
      which binds Fe(3+) less strongly owing to resonance delocalization of the anilino
      lone pair into the benzophenone pi-system. The release of Fe(3+) upon photolysis
      of FerriCast also was evaluated using a previously reported turn-on fluorescent
      sensor that utilizes the same macrocyclic ligand (4-(1-oxa-4,10-dithia-7-aza
      cyclododec-7-yl)phenyl, AT(2)12C4). In contrast to the original reports on
      AT(2)12C4-based Fe(3+) sensors, FerriCast does not interact with ferric iron in
      aqueous solution. Introduction of oxygen containing solvents (MeOH, H(2)O, DMSO,
      MES, and phosphate buffers) to CH(3)CN solutions of metalated FerriCast lead to
      rapid decomplexation as measured by UV-visible spectroscopy. Further
      investigations contradicted the published conclusions on the aqueous coordination
      chemistry of AT(2)12C4, but also confirmed the unique and unexpected selectivity
      of the macrocycle for Fe(3+) in nonaqueous solvents. The crystallographic
      analysis of [Cu(AT(2)12C4)Cl](+) provides a rare example of a bifurcated hydrogen
      bond, and evidence for redox chemistry with the ligand. Spectrophotometric
      analysis of the model ligand with redox active metal ions provide evidence for
      AT(2)12C4(*+), a quasi-stable species the presence of which suggests caution
      should be taken when evaluating the interaction of aniline-containing systems
      with redox active metal ions.

PMID- 20047294
TI  - Electronic structure of selected FeNO7 complexes in heme and non-heme
      architectures: a density functional and multireference ab initio study.
AB  - The multiconfigurational CASSCF/CASPT2 approach, along with various functionals
      of density functional theory, is applied to selected iron(II)-nitrosyl
      ({FeNO}(7)) complexes, both with heme and nonheme groups. The energetics of the
      lowest doublet and quartet spin states at the correlated ab initio (CASPT2) level
      is presented for the first time. Comparison of the CASSCF and (unrestricted) DFT
      spin densities indicates that the nonhybrid functionals yield the spin densities
      most closely to the ab initio ones. The analysis of the multiconfigurational
      CASSCF wave function in terms of the localized active orbitals allows one to
      resolve the nature of Fe-NO bonding as a mixture of Fe(II)-NO(0) and Fe(III)-NO(
      ) resonance structures (in comparable contributions) for both spin states and
      various ligands.

PMID- 20047291
TI  - Phosphoproteomics for the masses.
AB  - Protein phosphorylation serves as a primary mechanism of signal transduction in
      the cells of biological organisms. Technical advancements over the last several
      years in mass spectrometry now allow for the large-scale identification and
      quantitation of in vivo phosphorylation at unprecedented levels. These
      developments have occurred in the areas of sample preparation, instrumentation,
      quantitative methodology, and informatics so that today, 10 000-20 000
      phosphorylation sites can be identified and quantified within a few weeks. With
      the rapid development and widespread availability of such data, its translation
      into biological insight and knowledge is a current obstacle. Here we present an
      overview of how this technology came to be and is currently applied, as well as
      future challenges for the field.

PMID- 20047295
TI  - Chemical-text hybrid search engines.
AB  - As the amount of chemical literature increases, it is critical that researchers
      be enabled to accurately locate documents related to a particular aspect of a
      given compound. Existing solutions, based on text and chemical search engines
      alone, suffer from the inclusion of "false negative" and "false positive"
      results, and cannot accommodate diverse repertoire of formats currently available
      for chemical documents. To address these concerns, we developed an approach
      called Entity-Canonical Keyword Indexing (ECKI), which converts a chemical entity
      embedded in a data source into its canonical keyword representation prior to
      being indexed by text search engines. We implemented ECKI using Microsoft Office
      SharePoint Server Search, and the resultant hybrid search engine not only
      supported complex mixed chemical and keyword queries but also was applied to both
      intranet and Internet environments. We envision that the adoption of ECKI will
      empower researchers to pose more complex search questions that were not readily
      attainable previously and to obtain answers at much improved speed and accuracy.

PMID- 20047296
TI  - Comparison of the type of liposome involving cytokine production induced by non
      CpG Lipoplex in macrophages.
AB  - To improve the transfection efficiency of plasmid DNA (pDNA) into cells, various
      types of cationic liposome have been used to prepare pDNA/cationic liposome
      complexes (lipoplexes). It is well-known that lipoplexes induce a large amount of
      proinflammatory cytokines because unmethylated CpG dinucleotides (CpG motifs)
      abundantly present in pDNA are recognized by Toll-like receptor-9 (TLR9)
      expressed in immune cells such as macrophages and dendritic cells. This
      nonspecific cytokine production is problematic in nonviral gene therapy.
      Moreover, recent studies have demonstrated that lipoplexes induce not only
      proinflammatory cytokines but also another type of cytokine, type I interferons
      (IFNs), irrespective of the frequency of CpG motifs in DNA and the expression of
      TLR9. To gain more insight into the CpG motif- and TLR9-independent induction of
      type I IFNs and proinflammatory cytokines by lipoplex, macrophage activation was
      evaluated in vitro using various cationic liposomes complexed with pDNA
      containing no CpG motifs. The production of IFN-beta, TNF-alpha and IL-6 by
      lipoplex was confirmed to be induced independently of the interaction between CpG
      DNA and TLR9 in macrophages from TLR9-knockout mice. Then, the release of the
      cytokines, the mRNA expression of Z-DNA binding protein-1 (Zbp1), a cytosolic
      double-stranded DNA sensor, and the cellular uptake of pDNA were examined in a
      macrophage-like cell line, RAW264.7. The level of cytokine production and the
      increase in the Zbp1 mRNA varied depending on the type of cationic liposome used.
      A good correlation was observed between the cytokine level and the Zbp1 mRNA. A
      confocal microscopic study using fluorescently labeled pDNA complexes showed that
      the complexes that released a lot of cytokines showed an enhanced distribution of
      pDNA-derived fluorescence into the cytosol. These results suggest that different
      intracellular trafficking derived from the type of liposomes determines the
      recognition of pDNA by ZBP1 after uptake of lipoplexes by the macrophages,
      followed by the release of type I IFNs and inflammatory cytokines. The present
      study demonstrates that cationic liposomes should be selected based on these
      findings for optimization of DNA-based therapies using lipoplexes.

PMID- 20047297
TI  - Copper-catalyzed annulation of 2-formylazoles with o-aminoiodoarenes.
AB  - In the presence of catalytic CuI and sparteine, 2-formylpyrroles can be annulated
      with o-aminoiodoarenes to give substituted pyrrolo[1,2-a]quinoxalines and related
      heterocycles. The reaction also works for annulation of 2-formylindoles, 2
      formylimidazole, 2-formylbenzimidazole, and a 3-formylpyrazole.

PMID- 20047299
TI  - Excited-state intramolecular proton transfer of naphthalene-fused 2-(2'
      hydroxyaryl)benzazole family.
AB  - Intramolecularly hydrogen-bonded organic compounds often exhibit fluorescence
      emission at considerably longer wavelengths than typical fluorescence as a result
      of excited-state intramolecular proton transfer (ESIPT). The structure-property
      relationship of such ESIPT molecules, however, remains obscure. The present
      article reports the excited-state dynamics of a new family of ESIPT molecules, 2
      (2'-hydroxynaphthyl)benzazoles 1-3, based on steady-state and time-resolved
      spectroscopy measurements. In comparison with the parent compound HBO, all three
      compounds 1-3 exhibited absorption bands at longer wavelengths and emitted
      fluorescence from the excited keto-tautomer K* at shorter wavelengths, indicating
      that the introduction of a naphthalene ring increases the energy gap between the
      ground and excited states for the keto-tautomer despite the expansion of the
      aromatic ring. Time-resolved fluorescence spectra revealed dual emission for
      compounds 1 and 3, consisting of two distinct fluorescence bands originating from
      K* and the excited rotamer E'*, whereas 2 exhibited fluorescence only from the K*
      state. In the transient absorption spectra, both the T-T absorption band and the
      ground state absorption band of the Z-keto tautomer were observed for 1, whereas
      only the T-T absorption band was observed for 2 and only the Z-keto tautomer band
      was observed for 3.

PMID- 20047300
TI  - Adjacent pulsed nanoelectrospray ionization emitters for the alternating
      generation of ions of opposite polarity.
AB  - An approach that allows for adjacent closely spaced nanoelectrospray ionization
      (nESI) emitters to be pulsed alternately to generate ions of opposite polarity
      for transmission through a common interface is described. The potential
      difference between two or more nESI emitters in close proximity is minimized by
      applying the same polarity to both emitters at any given point in time but with
      the magnitude of only the active emitter's potential being sufficiently high to
      sustain a stable spray. The reduced difference in potential between emitters
      allows the distance between emitters to be decreased to within a few millimeters
      so that compromises imposed by the use of multiple emitters for the generation of
      ions from distinct solutions using a common atmosphere interface are minimized.

PMID- 20047301
TI  - Intramolecular chalcogen-tin interactions in [(o-MeEC6H4)CH2]2SnPh(2-n)Cl(n) (E =
      S, O, CH2; n = 0, 1, 2) and intermolecular chlorine-tin interactions in the meta-
      and para-methoxy isomers.
AB  - Organotin(IV) compounds of the type [(o-MeEC(6)H(4))CH(2)](2)SnPh(2-n)Cl(n) were
      synthesized, E = O, n = 0 (1), n = 1 (2), and n = 2 (3); E = S, n = 0 (4), n = 1
      (5), and n = 2 (6); and E = CH(2), n = 0 (7), n = 1 (8), and n = 2 (9). The
      dichloro compounds 3 and 6 have been investigated by single-crystal X-ray
      diffraction and exhibit bicapped tetrahedral geometry at the tin atom as a
      consequence of significant intramolecular Sn...O (3) and Sn...S (6) secondary
      bonding, in monomolecular units. Compound 3, when crystallized from a hexane/THF
      solvent mixture, shows two different conformers, 3' and 3'', in the crystal
      structure; 3' has two equivalent Sn...O interactions, while 3'' has two
      nonequivalent Sn...O interactions. Upon the recrystallization of 3 from hexane,
      only a single structural form is observed, 3'. The Sn...E distances in 3', 3'',
      and 6 are 71.3, 73.5 and 72.9, and 76.3% of the SigmavdW radii, respectively. The
      meta- and para-substituted isomers of 3 (10, 11) exhibit a distortion at the tin
      atom due to self-association via intermolecular Sn...Cl interactions, resulting
      in polymeric structures. (119)Sn NMR spectroscopy suggests that the
      intramolecular Sn...E interactions persist in solution for the dichloride
      compounds 3 and 6.

PMID- 20047302
TI  - Inhibition of breast cancer cell growth and invasiveness by dual silencing of HER
      2 and VEGF.
AB  - Overexpression of HER-2 accounts for approximately 25% of all breast cancer
      cases, while 87.7% of HER-2 positive breast cancers are associated with
      upregulated VEGF. The objective of this study is to explore the combination
      therapy of blocking HER-2 and VEGF expressions simultaneously using siRNA. This
      is the first report to examine the effect of dual silencing of HER-2 and VEGF
      genes on tumor growth and invasiveness. We have designed nine HER-2 siRNAs and
      ten VEGF siRNAs, and identified potent siRNA which can silence the target gene up
      to 75-83.5%. The most potent HER-2 and VEGF siRNAs were used to conduct
      functional studies in HER-2 positive breast cancer cells. Tumor invasiveness
      properties including cell morphology change, in vitro migration, cell spreading,
      and adhesion to ECM were evaluated. In addition, cell proliferation and apoptosis
      were examined after the siRNA treatment. Our data demonstrated for the first time
      that HER-2 siRNA could inhibit cell migration and invasion abilities. Combination
      of HER-2 and VEGF siRNAs exhibited synergistic silencing effect on VEGF. Both HER
      2 siRNA and VEGF siRNA showed significant inhibition on cell migration and
      proliferation. HER-2 siRNA also demonstrated dramatic suppression on cell
      spreading and adhesion to ECM, as well as induction of apoptosis. Dual silencing
      of HER-2 and VEGF exhibited significant cell morphology change, and substantial
      suppression on migration, spreading, cell adhesion, and proliferation. Our
      observations suggested that HER-2 positive breast cancer may be more effectively
      treated by dual inhibition of HER-2 and VEGF gene expressions using siRNA.

PMID- 20047304
TI  - Helical carbon nanotubes: catalytic particle size-dependent growth and magnetic
      properties.
AB  - The exact knowledge of helical carbon nanotube (HCNT) growth mechanism has not
      yet been completely clarified, and effective synthesis of high-purity helical
      carbon nanotubes in high yield still remains a tremendous challenge. In this
      study, HCNTs were synthesized via a catalytic chemical vapor deposition method
      using Fe nanoparticles as catalysts. We performed systematic experiments to
      investigate the specific effect of catalytic particle size (CPS) on the selective
      growth of HCNTs, such as on the morphology, yield, mobility of carbon atoms, and
      HCNT purity of carbon products. Our study showed that the CPS plays a key role in
      the selectivity to HCNTs, yield, and morphology of the carbon products, and a
      small catalytic particle is favorable to HCNT formation. We hope that this result
      may give a beneficial suggestion to obtain highly pure HCNTs. A CPS-dependent
      growth mechanism for HCNTs was finally proposed. Magnetic measurements
      demonstrated that the HCNTs are ferromagnetic properties and show high
      magnetization at room temperature.

PMID- 20047303
TI  - Visualizing water molecules in transmembrane proteins using radiolytic labeling
      methods.
AB  - Essential to cells and their organelles, water is both shuttled to where it is
      needed and trapped within cellular compartments and structures. Moreover, ordered
      waters within protein structures often colocalize with strategically placed polar
      or charged groups critical for protein function, yet it is unclear if these
      ordered water molecules provide structural stabilization, mediate conformational
      changes in signaling, neutralize charged residues, or carry out a combination of
      all these functions. Structures of many integral membrane proteins, including G
      protein-coupled receptors (GPCRs), reveal the presence of ordered water molecules
      that may act like prosthetic groups in a manner quite unlike bulk water.
      Identification of "ordered" waters within a crystalline protein structure
      requires sufficient occupancy of water to enable its detection in the protein's X
      ray diffraction pattern, and thus, the observed waters likely represent a subset
      of tightly bound functional waters. In this review, we highlight recent studies
      that suggest the structures of ordered waters within GPCRs are as conserved (and
      thus as important) as conserved side chains. In addition, methods of radiolysis,
      coupled to structural mass spectrometry (protein footprinting), reveal dynamic
      changes in water structure that mediate transmembrane signaling. The idea of
      water as a prosthetic group mediating chemical reaction dynamics is not new in
      fields such as catalysis. However, the concept of water as a mediator of
      conformational dynamics in signaling is just emerging, because of advances in
      both crystallographic structure determination and new methods of protein
      footprinting. Although oil and water do not mix, understanding the roles of water
      is essential to understanding the function of membrane proteins.

PMID- 20047305
TI  - Sulfonation of alkyl phenyl ether self-assembled monolayers.
AB  - The sulfonation of phenyl ether decorated self-assembled monolayers (SAMs) was
      studied with an eye toward creating surfaces with a particularly high negative
      charge density based on a close-packed array of phenyl rings with more than one
      sulfonic acid group per molecule. The product distribution and kinetics of this
      process were studied by ultraviolet, infrared, and photoelectron spectroscopies
      and by monitoring changes in the thickness and wetting properties of the SAM. The
      sulfonation chemistry could be effected without undermining monolayer integrity
      and the isomer distribution of ortho- and para-monosulfonated material, along
      with the percentages of mono- and disulfonated molecules could be established
      throughout the process. As doubly sulfonated molecules appeared, the reaction
      slowed drastically. Ultimately, sulfonation stops completely with approximately
      60% of the molecules disulfonated and 20% each of the two monosulfonated isomers.
      This striking constraint on monolayer reactivity and the relationship between the
      surface chemistry and variations in SAM structure are discussed.

PMID- 20047306
TI  - Roles for cationic residues at the quinolinic acid binding site of quinolinate
      phosphoribosyltransferase.
AB  - Quinolinic acid phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) forms
      nicotinate mononucleotide (NAMN) from quinolinic acid (QA) and 5-phosphoribosyl 1
      pyrophosphate (PRPP). Previously determined crystal structures of QAPRTase.QA and
      QAPRTase.PA.PRPP complexes show positively charged residues (Arg118, Arg152,
      Arg175, Lys185, and His188) lining the QA binding site. To assess the roles of
      these residues in the Salmonella typhimurium QAPRTase reaction, they were
      individually mutated to alanine and the recombinant proteins overexpressed and
      purified from a recombineered Escherichia coli strain that lacks the QAPRTase
      gene. Gel filtration indicated that the mutations did not affect the dimeric
      aggregation state of the enzymes. Arg175 is critical for the QAPRTase reaction,
      and its mutation to alanine produced an inactive enzyme. The k(cat) values for
      R152A and K185A were reduced by 33-fold and 625-fold, and binding affinity of
      PRPP and QA to the enzymes decreased. R152A and K185A mutants displayed 116-fold
      and 83-fold increases in activity toward the normally inactive QA analogue,
      nicotinic acid (NA), indicating roles for these residues in defining the
      substrate specificity of QAPRTase. Moreover, K185A QAPRTase displayed a 300-fold
      higher k(cat)/K(m) for NA over the natural substrate QA. Pre-steady-state
      analysis of K185A with QA revealed a burst of nucleotide formation followed by a
      slower steady-state rate, unlike the linear kinetics of WT. Intriguingly, pre
      steady-state analysis of K185A with NA produced a rapid but linear rate for NAMN
      formation. The result implies a critical role for Lys185 in the chemistry of the
      QAPRTase intermediate. Arg118 is an essential residue that reaches across the
      dimer interface. Mutation of Arg118 to alanine resulted in 5000-fold decrease in
      k(cat) value and a decrease in the binding affinity of QA and PRPP to R152A.
      Equimolar mixtures of R118A with inactive or virtually inactive mutants produced
      approximately 50% of the enzymatic activity of WT, establishing an interfacial
      role for Arg118 during catalysis.

PMID- 20047307
TI  - Interactions at the 2 and 5 positions of 5-phosphoribosyl pyrophosphate are
      essential in Salmonella typhimurium quinolinate phosphoribosyltransferase.
AB  - Quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) catalyzes an
      unusual phosphoribosyl transfer that is linked to a decarboxylation reaction to
      form the NAD precursor nicotinate mononucleotide, carbon dioxide, and
      pyrophosphate from quinolinic acid (QA) and 5-phosphoribosyl 1-pyrophosphate
      (PRPP). Structural studies and sequence similarities with other PRTases have
      implicated Glu214, Asp235, Lys153, and Lys284 in contributing to catalysis
      through direct interaction with PRPP. The four residues were substituted by site
      directed mutagenesis. A nadC deletant form of BL21DE3 was created to eliminate
      trace contamination by chromosomal QAPRTase. The mutant enzymes were readily
      purified and retained their dimeric aggregation state on gel filtration.
      Substitution of Lys153 with Ala resulted in an inactive enzyme, indicating its
      essential nature. Mutation of Glu214 to Ala or Asp caused at least a 4000-fold
      reduction in k(cat), with 10-fold increases in K(m) and K(D) values for PRPP.
      However, mutation of Glu214 to Gln had only modest effects on ligand binding and
      catalysis. pH profiles indicated that the deprotonated form of a residue with
      pK(a) of 6.9 is essential for catalysis. The WT-like pH profile of the E214Q
      mutant indicated that Glu214 is not that residue. Mutation of Asp235 to Ala did
      not affect ligand binding or catalysis. Mutation of Lys284 to Ala decreased
      k(cat) by 30-fold and increased K(m) and K(D) values for PRPP by 80-fold and at
      least 20-fold, respectively. The study suggests that Lys153 is necessary for
      catalysis and important for PRPP binding, Glu214 provides a hydrogen bond
      necessary for catalysis but does not act as a base or electrostatically to
      stabilize the transition state, Lys284 is involved in PRPP binding, and Asp235 is
      not essential.

PMID- 20047308
TI  - Ultrafast dynamics of resonance energy transfer in myoglobin: probing local
      conformation fluctuations.
AB  - We report here our systematic characterization of resonance energy transfer
      between intrinsic tryptophan and the prosthetic heme group in myoglobin in order
      to develop a novel energy-transfer pair as a molecular ruler in heme proteins to
      study local conformation fluctuations. With site-directed mutagenesis, we
      designed four tryptophan mutants along the A-helix of myoglobin and each mutant
      contains only a single tryptophan-heme energy-transfer pair. With femtosecond
      resolution, we observed, even at separation distances of 15-25 A, ultrafast
      energy transfer in tens to hundreds of picoseconds. On these time scales, the
      donor and acceptor cannot be randomized and the orientation factor in Forster
      energy transfer is highly restricted. Thus, direct measurement of the orientation
      factor changes at different mutation sites reveals relative local structure
      flexibility and conformation fluctuations as particularly demonstrated here for
      positions of tryptophan 7 and 14. More importantly, the local environment
      relaxation occurs on the similar time scales of the energy transfer dynamics,
      resulting in a nonequilibrium dynamic process. With femtosecond- and wavelength
      resolved fluorescence dynamics, we are able to determine the time scales of such
      nonequilibrium energy-transfer dynamics and elucidate the mechanism of the
      nonexponential energy-transfer dynamics caused by local dynamic heterogeneity
      and/or local environment relaxation.

PMID- 20047309
TI  - New nucleotide analogues with enhanced signal properties.
AB  - We describe synthesis and testing of a novel type of dye-modified nucleotides
      which we call macromolecular nucleotides (m-Nucs). Macromolecular nucleotides
      comprise a nucleotide moiety, a macromolecular linear linker, and a large
      macromolecular ligand carrying multiple fluorescent dyes. With incorporation of
      the nucleotide moiety into the growing nucleic acid strand during enzymatic
      synthesis, the macromolecular ligand together with the coupled dyes is bound to
      the nucleic acid. By the use of this new class of modified nucleotides, signals
      from multiple dye molecules can be obtained after a single enzymatic
      incorporation event. The modified nucleotides are considered especially useful in
      the fields of nanobiotechnology, where signal stability and intensity is a
      limiting factor.

PMID- 20047310
TI  - Experimental and computational studies indicate specific binding of pVHL protein
      to Aurora-A kinase.
AB  - Overexpression of Aurora-A kinase is commonly detected in many cancers, whereas
      the von Hippel-Lindau protein (pVHL) is frequently mutated or absent in renal
      cell carcinoma and is involved in the Ub proteasome complex, an important
      degradation pathway. In order to establish a link between Aurora-A overexpression
      and lack of pVHL protein, we hypothesized that pVHL regulates Aurora-A expression
      through a physical interaction. We present the first evidence, from both
      biological assays and computational biology techniques, that human pVHL binds
      strongly to Aurora-A kinase. Extensive molecular modeling, docking, and dynamic
      simulations demonstrate that the structure of the pVHL protein would allow it to
      bind to the TPX2 binding region of Aurora-A. In view of Aurora-A's importance as
      a therapeutic target for the treatment of cancer, this observation provides novel
      insights into the Aurora-A/pVHL pathway. In addition, the detailed Aurora-A/pVHL
      binding structure obtained will be valuable for the design of future Aurora-A
      inhibitors as therapeutic agents.

PMID- 20047312
TI  - Uncertainty analysis of the nonideal competitive adsorption-donnan model: effects
      of dissolved organic matter variability on predicted metal speciation in soil
      solution.
AB  - Ion binding models such as the nonideal competitive adsorption-Donnan model (NICA
      Donnan) and model VI successfully describe laboratory data of proton and metal
      binding to purified humic substances (HS). In this study model performance was
      tested in more complex natural systems. The speciation predicted with the NICA
      Donnan model and the associated uncertainty were compared with independent
      measurements in soil solution extracts, including the free metal ion activity and
      fulvic (FA) and humic acid (HA) fractions of dissolved organic matter (DOM).
      Potentially important sources of uncertainty are the DOM composition and the
      variation in binding properties of HS. HS fractions of DOM in soil solution
      extracts varied between 14 and 63% and consisted mainly of FA. Moreover, binding
      parameters optimized for individual FA samples show substantial variation. Monte
      Carlo simulations show that uncertainties in predicted metal speciation, for
      metals with a high affinity for FA (Cu, Pb), are largely due to the natural
      variation in binding properties (i.e., the affinity) of FA. Predictions for
      metals with a lower affinity (Cd) are more prone to uncertainties in the fraction
      FA in DOM and the maximum site density (i.e., the capacity) of the FA. Based on
      these findings, suggestions are provided to reduce uncertainties in model
      predictions.

PMID- 20047311
TI  - Synthesis and gene delivery of poly(amido amine)s with different branched
      architecture.
AB  - A general strategy to improve the transfection efficiency as well as lower the
      cytotoxicity for polycationic vectors has been developed. Through the
      polycondensation addition of N,N'-methylene bisacrylamide and 1-(2
      aminoethyl)piperazine in a water/N,N-dimethylformamide cosolvent, a series of
      cationic poly(amido amine)s with same repeating units but different branched
      architecture have been prepared. With the increase in branched architecture, the
      cationic polymers become more and more compact, accompanied by the enhancement of
      primary and tertiary amino groups. Therefore, the buffering capacities and DNA
      condensation capabilities of cationic poly(amido amine)s are strengthened
      greatly, whereas the correspondent cytotoxicity decreases. Correspondingly, the
      transfection efficiency is improved by more than three orders of magnitude. The
      results of this study indicate that the gene delivery can be readily regulated by
      only changing the branched architecture of polycations.

PMID- 20047313
TI  - Synthesis, substitution kinetics, and electrochemistry of the first
      tetrathiafulvalene-containing beta-diketonato complexes of rhodium(I).
AB  - The synthesis of the first rhodium(I) cyclooctadiene complexes containing
      tetrathiafulvalene (TTF) groups substituted on a beta-diketonato ligand in either
      the methine position (3 position), [Rh(cod)(H(3)CCOC{S-TTF-(MeS)(3)}COCH(3))]
      (3), or terminal position (1 position), [Rh(cod){(Me(3)-TTF)COCHCOCH(3)}] (4), is
      reported. The effect of the beta-diketonato substitution position on the kinetics
      of substitution of the TTF-containing beta-diketonato ligand with 1,10
      phenanthroline from 3 and 4 to give [Rh(cod)(phen)](+), as well as on the
      electrochemical properties of 3 and 4, was investigated. Second-order
      substitution rate constants, k(2), in methanol were found to be almost
      independent of the substitution position, with 4 (k(2) = 2.09 x 10(3) dm(3) mol(
      1) s(-1)) reacting only about twice as fast as 3. An appreciable solvent pathway
      in the substitution mechanism was only observed for 4 with k(s) = 42 s(-1). A
      complete mechanism for both substitution reactions is proposed. The
      electrochemistry of 3 and 4 in CH(2)Cl(2)/0.10 mol dm(-3)
      [N((n)Bu)(4)][B(C(6)F(5))(4)] showed three redox processes. Two of these were
      electrochemically reversible and are associated with the redox-active TTF group.
      For 3, TTF-based formal reduction potentials, E degrees', were observed at 0.082
      and 0.659 V vs Fc/Fc(+), respectively; 4 exhibited them at -0.172 and 0.703 V vs
      Fc/Fc(+) at a scan rate of 100 mV s(-1). A Rh(II)/Rh(I) redox couple was observed
      at E degrees' = 0.89 V for 3, after both TTF oxidations were completed, and at
      0.51 V for 4; this is between the two TTF redox processes. The more difficult
      oxidation of the Rh(I) center of 3 indicates more effective electron-withdrawing
      from the Rh(I) center to the first-oxidized TTF(+) group at the methine position
      of the beta-diketonato ligand of 3(+) than to the terminal-substituted TTF(+)
      group in 4(+).

PMID- 20047314
TI  - Detection of alternative splice variants at the proteome level in Aspergillus
      flavus.
AB  - Identification of proteins from proteolytic peptides or intact proteins plays an
      essential role in proteomics. Researchers use search engines to match the
      acquired peptide sequences to the target proteins. However, search engines depend
      on protein databases to provide candidates for consideration. Alternative
      splicing (AS), the mechanism where the exon of pre-mRNAs can be spliced and
      rearranged to generate distinct mRNA and therefore protein variants, enable
      higher eukaryotic organisms, with only a limited number of genes, to have the
      requisite complexity and diversity at the proteome level. Multiple alternative
      isoforms from one gene often share common segments of sequences. However, many
      protein databases only include a limited number of isoforms to keep minimal
      redundancy. As a result, the database search might not identify a target protein
      even with high quality tandem MS data and accurate intact precursor ion mass. We
      computationally predicted an exhaustive list of putative isoforms of Aspergillus
      flavus proteins from 20 371 expressed sequence tags to investigate whether an
      alternative splicing protein database can assign a greater proportion of mass
      spectrometry data. The newly constructed AS database provided 9807 new
      alternatively spliced variants in addition to 12 832 previously annotated
      proteins. The searches of the existing tandem MS spectra data set using the AS
      database identified 29 new proteins encoded by 26 genes. Nine fungal genes
      appeared to have multiple protein isoforms. In addition to the discovery of
      splice variants, AS database also showed potential to improve genome annotation.
      In summary, the introduction of an alternative splicing database helps identify
      more proteins and unveils more information about a proteome.

PMID- 20047315
TI  - EPR and Mossbauer spectroscopy show inequivalent hemes in tryptophan dioxygenase.
AB  - Tryptophan 2,3-dioxygenase (TDO) is an essential enzyme in the pathway of NAD
      biosynthesis and important for all living organisms. TDO catalyzes oxidative
      cleavage of the indole ring of L-tryptophan (L-Trp), converting it to N
      formylkynurenine (NFK). The crystal structure of TDO shows a dimer of dimer
      quaternary structure of the homotetrameric protein. The four catalytic sites of
      the protein, one per subunit, contain a heme that catalyzes the activation and
      insertion of dioxygen into L-Trp. Because of the alpha(4) structure and because
      only one type of heme center has been identified in previous spectroscopic
      studies, the four hemes sites have been presumed to be equivalent. The present
      work demonstrates that the heme sites of TDO are not equivalent. Quantitative
      interpretation of EPR and Mossbauer spectroscopic data indicates the presence of
      two dominant inequivalent heme species in reduced and oxidized states of the
      enzyme, which is consistent with a dimer of dimer protein quaternary structure
      that now extends to the electronic properties of the hemes. The electronic
      properties of the hemes in the reduced state of TDO change significantly upon L
      Trp addition, which is attributed to a change in the protonation state of the
      proximal histidine to the hemes. The binding of O(2) surrogates NO or CO shows
      two inequivalent heme sites. The heme-NO complexes are 5- and 6-coordinate
      without L-Trp, and both 6-coordinate with L-Trp. NO can be selectively
      photodissociated from only one of the heme-NO sites and only in the presence of L
      Trp. Cryoreduction of TDO produces a novel diamagnetic heme species, tentatively
      assigned as a reduced heme-OH complex. This work presents a new description of
      the heme interactions with the protein, and with the proximal His, which must be
      considered during the general interpretation of physical data as it relates to
      kinetics, mechanism, and function of TDO.

PMID- 20047316
TI  - Catalytic alkylation of methyl-N-heteroaromatics with alcohols.
AB  - A novel catalytic C-C coupling reaction in which N-heteroaromatic-substituted
      methyl groups are efficiently alkylated using primary alcohols is introduced. The
      synthesis protocol is based on iridium catalysts and most likely relies on the
      "borrowing hydrogen" or "hydrogen autotransfer" mechanism. A variety of substrate
      combinations can readily be employed in this reaction, including pyrimidines,
      pyrazines, pyridazines, and even fairly activated 2- and 4-picolines.

PMID- 20047317
TI  - Solvent effects on catalysis by Escherichia coli dihydrofolate reductase.
AB  - Hydride transfer catalyzed by dihydrofolate reductase (DHFR) has been described
      previously within an environmentally coupled model of hydrogen tunneling, where
      protein motions control binding of substrate and cofactor to generate a tunneling
      ready conformation and modulate the width of the activation barrier and hence the
      reaction rate. Changes to the composition of the reaction medium are known to
      perturb protein motions. We have measured kinetic parameters of the reaction
      catalyzed by DHFR from Escherichia coli in the presence of various cosolvents and
      cosolutes and show that the dielectric constant, but not the viscosity, of the
      reaction medium affects the rate of reaction. Neither the primary kinetic isotope
      effect on the reaction nor its temperature dependence were affected by changes to
      the bulk solvent properties. These results are in agreement with our previous
      report on the effect of solvent composition on catalysis by DHFR from the
      hyperthermophile Thermotoga maritima. However, the effect of solvent on the
      temperature dependence of the kinetic isotope effect on hydride transfer
      catalyzed by E. coli DHFR is difficult to explain within a model, in which long
      range motions couple to the chemical step of the reaction, but may indicate the
      existence of a short-range promoting vibration or the presence of multiple nearly
      isoenergetic conformational substates of enzymes with similar but distinct
      catalytic properties.

PMID- 20047319
TI  - Influence of osmolytes and denaturants on the structure and enzyme activity of
      alpha-chymotrypsin.
AB  - Enzymes are very sensitive and highly complex systems, exhibiting a substantial
      degree of structural variability in their folded state. In the presence of
      cosolvents, the fluctuations among vast numbers of folded and unfolded
      conformations occur via many different pathways, and alternatively, enzymes can
      be stabilized or destabilized. To understand the contribution of osmolytes and
      denaturants on the stabilization, related to the associated structural changes
      and enzyme activity of alpha-chymotrypsin (CT), we have monitored differential
      scanning calorimeter (DSC), circular dichroism (CD), enzyme activity, and gel
      electrophoresis as a function of osmolyte or denaturant concentration. The
      present investigation compares the compatibility of osmolytes and deleterious
      effects of denaturants on the structure, function, and enzyme activity of CT.
      This comparison has provided new important insight on the contribution of
      cosolvent effects on protein folding/unfolding, enzyme activity, and
      understanding of protein-solvent interactions. Our DSC results reveal that the
      enthalpy change (DeltaH) and Gibbs free energy of change (DeltaG(u)) of CT in
      osmolyte (trimethylamine N-oxide (TMAO), betaine, sarcosine, proline, and
      sucrose) increase linearly as osmolyte concentration increases, while those
      values decrease sharply in the presence of denaturants (urea and guanidine
      hydrochloride (GdnHCl)). The modifications in the secondary structure of this
      beta/beta protein, as quantified by the CD spectra, showed reasonable enhancement
      for beta-strands in the presence of the osmolytes as compared to buffer, which
      contributes to its stabilization power. Evidently, we observed that naturally
      occurring osmolytes have a dominant contribution to the stabilization of CT while
      not enhancing its enzyme activity. In contrast, our results revealed that the
      denaturants enhanced the surface of the enzyme by binding to the surface of CT,
      which leads to zero enzyme activity.

PMID- 20047320
TI  - Hyperfine resolved Fourier transform microwave and millimeter-wave spectroscopy
      of the iodomethyl radical, CH2I (X2B1).
AB  - Fourier-transform microwave and millimeter-wave spectra of the iodomethyl
      radical, CH(2)I, have been observed in the ground vibronic state in the frequency
      ranges 17-38 GHz and 200-610 GHz, respectively. The pi-electron radical was
      produced either by iodine abstraction from diiodomethane (CH(2)I(2)) or by
      hydrogen abstraction from iodomethane (CH(3)I). Seventy-three hyperfine resolved
      lines owing to the two hydrogen and to the iodine nuclei have been detected in
      the microwave region, including K(a) = 0 (ortho species) and K(a) = 1 (para
      species). No hyperfine splitting due to the hydrogen nuclei could be observed for
      the para species, directly confirming the planarity of the radical and that the
      ground electronic state is (2)B(1). More than 400 a-type transitions that span
      the values N' < or = 35, K(a) < or = 6, were detected. A global least-squares
      analysis of the measured lines was conducted and led to the determination of an
      exhaustive list of molecular constants. In particular, the sign of the Fermi
      contact constant of iodine was unambiguously determined to be negative, which is
      opposite to that of the other monosubstituted halomethyl radicals. This work
      allowed a systematic comparison of the structural and bonding properties among
      the CH(2)X analogues (where X = F, Cl, Br, and I) owing to the hyperfine coupling
      constants of both the hydrogen and halogen nuclei.

PMID- 20047322
TI  - Experimental determination of single CdSe nanowire absorption cross sections
      through photothermal imaging.
AB  - Absorption cross sections ((sigma)abs) of single branched CdSe nanowires (NWs)
      have been measured by photothermal heterodyne imaging (PHI). Specifically, PHI
      signals from isolated gold nanoparticles (NPs) with known cross sections were
      compared to those of individual CdSe NWs excited at 532 nm. This allowed us to
      determine average NW absorption cross sections at 532 nm of (sigma)abs = (3.17 +/
      0.44) x 10(-11) cm2/microm (standard error reported). This agrees well with a
      theoretical value obtained using a classical electromagnetic analysis ((sigma)abs
      = 5.00 x 10(-11) cm2/microm) and also with prior ensemble estimates. Furthermore,
      NWs exhibit significant absorption polarization sensitivities consistent with
      prior NW excitation polarization anisotropy measurements. This has enabled
      additional estimates of the absorption cross section parallel ((sigma)abs) and
      perpendicular ((sigma)abs(perpendicular) to the NW growth axis, as well as the
      corresponding NW absorption anisotropy ((rho)abs). Resulting values of (sigma)abs
      = (5.6 +/- 1.1) x 10(-11) cm2/microm, (sigma)abs(perpendicular) = (1.26 +/- 0.21)
      x 10(-11) cm2/microm, and (rho)abs = 0.63+/- 0.04 (standard errors reported) are
      again in good agreement with theoretical predictions. These measurements all
      indicate sizable NW absorption cross sections and ultimately suggest the
      possibility of future direct single NW absorption studies.

PMID- 20047323
TI  - Enantioselective hydrogenation of alpha-aryloxy and alpha-alkoxy alpha,beta
      unsaturated carboxylic acids catalyzed by chiral spiro iridium/phosphino
      oxazoline complexes.
AB  - The iridium-catalyzed highly enantioselective hydrogenation of alpha-aryloxy and
      alpha-alkoxy-substituted alpha,beta-unsaturated carboxylic acids was developed.
      By using chiral spiro phosphino-oxazoline ligands, the hydrogenation proceeded
      smoothly to produce various alpha-aryloxy- and alpha-alkoxy-substituted
      carboxylic acids with extremely high enantioselectivities (ee up to 99.8%) and
      reactivities (TON up to 10,000) under mild conditions. The hydrogenation of alpha
      benzyloxy-substituted alpha,beta-unsaturated acids provided an efficient
      alternative for the synthesis of chiral alpha-hydroxy acids after an easy
      deprotection. A mechanism involving a catalytic cycle between Ir(I) and Ir(III)
      was proposed on the basis of the coordination model of the unsaturated acids with
      the iridium metal center. The rationality of the catalytic cycle, with an olefin
      dihydride complex as the key intermediate, was supported by the deuterium
      labeling studies. The X-ray diffraction analysis of the single crystal of
      catalyst revealed that the rigid and sterically hindered chiral environment
      created by the spiro phosphino-oxazoline ligands is the essential factor that
      permits the catalyst to obtain excellent chiral discrimination. A chiral
      induction model was suggested on the basis of the catalyst structure and the
      product configuration.

PMID- 20047324
TI  - Controlling the fenton reaction in wine.
AB  - The fate of hydrogen peroxide in a model wine system was studied under a
      competitive scenario in the presence of ferrous ions and sulfur dioxide. The
      metal-catalyzed reduction of hydrogen peroxide (H(2)O(2)), referred to as the
      Fenton reaction, yields hydroxyl radicals capable of oxidizing ethanol to
      acetaldehyde and is now thought to be a key step in nonenzymatic wine oxidation.
      It appears that sulfur dioxide (SO(2)) exerts its protective function in wine by
      scavenging hydrogen peroxide in oxidizing wine, thereby diverting peroxide from
      the Fenton route. In this study, the factors affecting the rate and outcome of
      hydroxyl radical-mediated ethanol oxidation were examined under wine conditions.
      The exclusion of oxygen in the model wine led to conditions wherein ferric ions
      (50 microM) were rapidly reduced, presumably by 1-hydroxyethyl radicals. This
      resulted in the complete stoichiometric conversion of H(2)O(2) (300 microM) to
      hydroxyl radicals, giving an equimolar concentration of acetaldehyde (
      approximately 300 microM). Surprisingly, the yield of acetaldehyde was markedly
      depressed in the presence of oxygen. The addition of a model phenol, 4
      methylcatechol (4-MeC; 12 mM), did not protect the ethanol from hydroxyl radical
      mediated oxidation under the conditions tested but rather appeared to slightly
      increase the rate of the Fenton reaction, perhaps by forming a complex with the
      added iron. The competition for H(2)O(2) in the presence of Fe(II) ions and SO(2)
      was also examined, and the effect of added 4-MeC, as well as dissolved oxygen,
      was investigated. Higher concentrations of 1-hydroxyethyl radicals, which were
      trapped by N-tert-butyl-alpha-phenylnitrone (PBN) and detected by electron
      paramagnetic resonance spectroscopy, were observed when oxygen was excluded and
      when 4-MeC was included.

PMID- 20047321
TI  - DNA-mediated charge transport in redox sensing and signaling.
AB  - The transport of charge through the DNA base-pair stack offers a route to carry
      out redox chemistry at a distance. Here we describe characteristics of this
      chemistry that have been elucidated and how this chemistry may be utilized within
      the cell. The shallow distance dependence associated with these redox reactions
      permits DNA-mediated signaling over long molecular distances in the genome and
      facilitates the activation of redox-sensitive transcription factors globally in
      response to oxidative stress. The long-range funneling of oxidative damage to
      sites of low oxidation potential in the genome also may provide a means of
      protection within the cell. Furthermore, the sensitivity of DNA charge transport
      to perturbations in base-pair stacking, as may arise with base lesions and
      mismatches, may be used as a route to scan the genome for damage as a first step
      in DNA repair. Thus, the ability of double-helical DNA in mediating redox
      chemistry at a distance provides a natural mechanism for redox sensing and
      signaling in the genome.

PMID- 20047326
TI  - Effects of hydration and oxygen vacancy on CO2 adsorption and activation on beta
      Ga2O3(100).
AB  - The effects of hydration and oxygen vacancy on CO(2) adsorption on the beta
      Ga(2)O(3)(100) surface have been studied using density functional theory slab
      calculations. Adsorbed CO(2) is activated on the dry perfect beta-Ga(2)O(3)(100)
      surface, resulting in a carbonate species. This adsorption is slightly
      endothermic, with an adsorption energy of 0.07 eV. Water is preferably adsorbed
      molecularly on the dry perfect beta-Ga(2)O(3)(100) surface with an adsorption
      energy of -0.56 eV, producing a hydrated perfect beta-Ga(2)O(3)(100) surface.
      Adsorption of CO(2) on the hydrated surface as a carbonate species is also
      endothermic, with an adsorption energy of 0.14 eV, indicating a slightly
      repulsive interaction when H(2)O and CO(2) are coadsorbed. The carbonate species
      on the hydrated perfect surface can be protonated by the coadsorbed H(2)O to a
      bicarbonate species, making the CO(2) adsorption exothermic, with an adsorption
      energy of -0.13 eV. The effect of defects on CO(2) adsorption and activation has
      been examined by creating an oxygen vacancy on the dry beta-Ga(2)O(3)(100)
      surface. The formation of an oxygen vacancy is endothermic, by 0.34 eV, with
      respect to a free O(2) molecule in the gas phase. Presence of the oxygen vacancy
      promoted the adsorption and activation of CO(2). In the most stable CO(2)
      adsorption configuration on the dry defective beta-Ga(2)O(3)(100) surface with an
      oxygen vacancy, one of the oxygen atoms of the adsorbed CO(2) occupies the oxygen
      vacancy site, and the CO(2) adsorption energy is -0.31 eV. Water favors
      dissociative adsorption at the oxygen vacancy site on the defective surface. This
      process is spontaneous, with a reaction energy of -0.62 eV. These results
      indicate that, when water and CO(2) are present in the adsorption system
      simultaneously, water will compete with CO(2) for the oxygen vacancy sites and
      impact CO(2) adsorption and conversion negatively.

PMID- 20047325
TI  - Blueberry supplementation improves memory in older adults.
AB  - The prevalence of dementia is increasing with expansion of the older adult
      population. In the absence of effective therapy, preventive approaches are
      essential to address this public health problem. Blueberries contain polyphenolic
      compounds, most prominently anthocyanins, which have antioxidant and anti
      inflammatory effects. In addition, anthocyanins have been associated with
      increased neuronal signaling in brain centers, mediating memory function as well
      as improved glucose disposal, benefits that would be expected to mitigate
      neurodegeneration. This study investigated the effects of daily consumption of
      wild blueberry juice in a sample of nine older adults with early memory changes.
      At 12 weeks, improved paired associate learning (p = 0.009) and word list recall
      (p = 0.04) were observed. In addition, there were trends suggesting reduced
      depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also
      compared the memory performances of the blueberry subjects with a demographically
      matched sample who consumed a berry placebo beverage in a companion trial of
      identical design and observed comparable results for paired associate learning.
      The findings of this preliminary study suggest that moderate-term blueberry
      supplementation can confer neurocognitive benefit and establish a basis for more
      comprehensive human trials to study preventive potential and neuronal mechanisms.

PMID- 20047327
TI  - Charge separation in a niobate nanosheet photocatalyst studied with photochemical
      labeling.
AB  - Photolabeling was employed to probe charge separation and the distribution of
      redox-active sites on the surface of nanosheets derived from the layered
      photocatalysts KCa(2)Nb(3)O(10). Electron microscopy reveals 1-50 nm particles of
      silver, gold, iridium oxide, and manganese dioxide particles and small atomically
      sized clusters of platinum and IrO(x) on the nanosheet surfaces and along the
      edges. The sizes, shapes, and particle densities vary with the deposition
      conditions, i.e., the precursor concentration and the presence of sacrificial
      agents. Overall, the study shows that photogenerated electrons and holes are
      accessible throughout the nanosheets, without evidence for spatial charge
      separation across the sheet.

PMID- 20047328
TI  - Capillary negative pressure measured by nanochannel collapse.
AB  - A new method is presented to measure capillarity-induced negative pressure.
      Negative pressures of several bars have been measured for five different liquids
      (ethanol, acetone, cyclohexane, aniline, and water) over a range of surface
      tension. Capillary negative pressure was measured in 79 +/- 3 nm silica
      nanochannels on the basis of the determination of the critical channel width for
      elastocapillary collapse of the flexible plate covering the channels. The results
      are consistent with the Young-Laplace equation.

PMID- 20047329
TI  - Self-assembled nanofibers of fluorescent zeolite L crystals and conjugated
      polymer.
AB  - Through this work, we present self-assembled structures which can be obtained by
      mixing surface modified dye loaded zeolite L crystals and cationic precursors of
      a conjugated polymer. The zeolite crystals are modified with anionic end groups
      which give the former a polyanionic character and allow a polyelectrolytic
      assembly. Microfluidic forces, introduced during the drying of a drop of water
      containing both polyelectrolytes casted on a clean glass substrate, and localized
      adsorption on the single zeolite crystal lead to the formation of micro- and
      nanofibers of highly ordered zeolite nanocrystals. As a result, the fibers
      display a very well polarized emission from the organic dye included into the
      nanochannels of the inorganic crystal. Playing on the relative concentrations of
      polycation and zeolites, and after thermal conversion of the polymer precursor,
      rigid and insoluble fibers with diameters ranging from less than 200 nm to a few
      micrometers are obtained.

PMID- 20047331
TI  - Design, synthesis, biological properties, and molecular modeling investigations
      of novel tacrine derivatives with a combination of acetylcholinesterase
      inhibition and cannabinoid CB1 receptor antagonism.
AB  - Pyrazolines 7-10 were designed as novel CB(1) receptor antagonists, which
      exhibited improved turbidimetric aqueous solubilities. On the basis of their
      extended CB(1) antagonist pharmacophore, hybrid molecules exhibiting cannabinoid
      CB(1) receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting
      activities were designed. The target compounds 12, 13, 20, and 21 are based on 1
      (tacrine) as the AChE inhibitor (AChEI) pharmacophore and two different CB(1)
      antagonistic pharmacophores. The imidazole-based 20 showed high CB(1) receptor
      affinity (48 nM) in combination with high CB(1)/CB(2) receptor subtype
      selectivity (>20-fold) and elicited equipotent AChE inhibitory activity as 1.
      Molecular modeling studies revealed the presence of a binding pocket in the AChE
      enzyme which nicely accommodates the CB(1) pharmacophores of the target compounds
      12, 13, 20, and 21.

PMID- 20047330
TI  - Small molecules and stem cells. Potency and lineage commitment: the new quest for
      the fountain of youth.

PMID- 20047332
TI  - Distal interactions within the par3-VE-cadherin complex.
AB  - par3 is a multiple-PDZ-containing scaffold protein that is central to the
      organization of an evolutionarily conserved cell polarity complex consisting of
      par3, par6, and aPKC. The ability of par3 PDZ domains to target various adhesion
      molecules and enzymes at the plasma membrane leads to the controlled localization
      of par6 and aPKC, which has firmly established its role in epithelial cell
      polarity. Of the numerous PDZ ligands associated with par3, interaction of its
      third PDZ domain with the class II ligand found within the C-terminal tail of
      vascular endothelial cadherin (VE-Cad) suggests a role in endothelial cell
      polarity as well, but the molecular details of the interaction are unknown.
      Previously determined structures of par3-PDZ3 bound to the class I ligand found
      within the C-terminal tail of the phosphoinositide phosphatase PTEN revealed two
      discrete binding sites: a canonical PDZ-ligand interaction site and a distal site
      involving charge-charge complements. Currently, it is unclear if par3-PDZ3
      employs both canonical and distal binding modes in its association with VE-Cad or
      if these modes are unique to the PTEN interaction, suggesting a possible
      mechanism for ligand specificity within the polarity network. The structure of
      par3-PDZ3 bound to the C-terminal tail of VE-Cad presented in this work shows
      that both canonical and distal interactions are utilized in binding. Biophysical
      measurements using fluorescence polarization and two-dimensional NMR implicate
      the intermolecular charge pairing of aspartic acid 777 (VE-Cad) and arginine 609
      (par3-PDZ3) as a crucial modulator of complex formation. Phosphorylation of VE
      Cad at serine 776 increases its affinity for par3, demonstrating that post
      translational modifications outside of the canonical carboxylate binding site can
      enhance PDZ-ligand interactions. Comparison of the VE-Cad and PTEN complexes
      highlights how the unique molecular architecture of par3-PDZ3 can accommodate
      both canonical and distal interaction modes that allow dual-class specificity for
      these two ligand types.

PMID- 20047333
TI  - Synthesis and crystal structure of 2'-se-modified guanosine containing DNA.
AB  - Selenium modification of nucleic acids is of great importance in X-ray crystal
      structure determination and functional study of nucleic acids. Herein, we
      describe a convenient synthesis of a new building block, the 2'-SeMe-modified
      guanosine (G(Se)) phosphoramidite, and report the first incorporation of the 2'
      Se-G moiety into DNA. The X-ray crystal structure of the 2'-Se-modified octamer
      DNA (5'-GTG(Se)TACAC-3') was determined at a resolution of 1.20 A. We also found
      that the 2'-Se modification points to the minor groove and that the modified and
      native structures are virtually identical. Furthermore, we observed that the 2'
      Se-G modification can significantly facilitate the crystal growth with respect to
      the corresponding native DNA.

PMID- 20047334
TI  - Cu-catalyzed N-alkynylation of imidazoles, benzimidazoles, indazoles, and
      pyrazoles using PEG as solvent medium.
AB  - A facile and efficient Cu(I)-catalyzed cross-coupling method is reported for the
      preparation of N-alkynyl or N-bromoalkenyl heteroarenes from bromoalkynes.
      Generally superior yields and functional group tolerance were obtained with
      microwave (MW) irradiation using imidazole, benzimidazole, pyrazole, and indazole
      substrates and poly(ethylene glycol) 400 (PEG400) as an additive. We speculate
      that PEG400 acts as both a Cu(I)-stabilizing ligand as well as a phase transfer
      solvent.

PMID- 20047335
TI  - Fenton-treated functionalized diamond nanoparticles as gene delivery system.
AB  - When raw diamond nanoparticles (Dnp, 7 nm average particle size) obtained from
      detonation are submitted to harsh Fenton-treatment, the resulting material
      becomes free of amorphous soot matter and the process maintains the
      crystallinity, reduces the particle size (4 nm average particle size), increases
      the surface OH population, and increases water solubility. All these changes are
      beneficial for subsequent Dnp covalent functionalization and for the ability of
      Dnp to cross cell membranes. Fenton-treated Dnps have been functionalized with
      thionine and the resulting sample has been observed in HeLa cell nuclei. A
      triethylammonium-functionalized Dnp pairs electrostatically with a plasmid having
      the green fluorescent protein gene and acts as gene delivery system permitting
      the plasmid to cross HeLa cell membrane, something that does not occur for the
      plasmid alone without assistance of polycationic Dnp.

PMID- 20047336
TI  - A novel method of production and biophysical characterization of the catalytic
      domain of yeast oligosaccharyl transferase.
AB  - Oligosaccharyl transferase (OT) is a multisubunit enzyme that catalyzes N-linked
      glycosylation of nascent polypeptides in the lumen of the endoplasmic reticulum.
      In the case of Saccharomyces cerevisiae, OT is composed of nine integral membrane
      protein subunits. Defects in N-linked glycosylation cause a series of disorders
      known as congenital disorders of glycosylation (CDG). The C-terminal domain of
      the Stt3p subunit has been reported to contain the acceptor protein recognition
      site and/or catalytic site. We report here the subcloning, overexpression, and a
      robust but novel method of production of the pure C-terminal domain of Stt3p at
      60-70 mg/L in Escherichia coli. CD spectra indicate that the C-terminal Stt3p is
      highly helical and has a stable tertiary structure in SDS micelles. The well
      dispersed two-dimensional (1)H-(15)N HSQC spectrum in SDS micelles indicates that
      it is feasible to determine the atomic structure by NMR. The effect of the
      conserved D518E mutation on the conformation of the C-terminal Stt3p is
      particularly interesting. The replacement of a key residue, Asp(518), located
      within the WWDYG signature motif (residues 516-520), led to a distinct tertiary
      structure, even though both proteins have similar overall secondary structures,
      as demonstrated by CD, fluorescence and NMR spectroscopies. This observation
      strongly suggests that Asp(518) plays a critical structural role, in addition to
      the previously proposed catalytic role. Moreover, the activity of the protein was
      confirmed by saturation transfer difference and nuclear magnetic resonance
      titration studies.

PMID- 20047337
TI  - NMR mapping of the IFNAR1-EC binding site on IFNalpha2 reveals allosteric changes
      in the IFNAR2-EC binding site.
AB  - All type I interferons (IFNs) bind to a common cell-surface receptor consisting
      of two subunits. IFNs initiate intracellular signal transduction cascades by
      simultaneous interaction with the extracellular domains of its receptor subunits,
      IFNAR1 and IFNAR2. In this study, we mapped the surface of IFNalpha2 interacting
      with the extracellular domain of IFNAR1 (IFNAR1-EC) by following changes in or
      the disappearance of the (1)H-(15)N TROSY-HSQC cross peaks of IFNalpha2 caused by
      the binding of the extracellular domain of IFNAR1 (IFNAR1-EC) to the binary
      complex of IFNalpha2 with IFNAR2-EC. The NMR study of the 89 kDa complex was
      conducted at pH 8 and 308 K using an 800 MHz spectrometer. IFNAR1 binding
      affected a total of 47 of 165 IFNalpha2 residues contained in two large patches
      on the face of the protein opposing the binding site for IFNAR2 and in a third
      patch located on the face containing the IFNAR2 binding site. The first two
      patches form the IFNAR1 binding site, and one of these matches the IFNAR1 binding
      site previously identified by site-directed mutagenesis. The third patch
      partially matches the IFNalpha2 binding site for IFNAR2-EC, indicating allosteric
      communication between the binding sites for the two receptor subunits.

PMID- 20047338
TI  - Reversible dimerization of Aequorea victoria fluorescent proteins increases the
      dynamic range of FRET-based indicators.
AB  - Fluorescent protein (FP)-based Forster resonance energy transfer (FRET)
      technology is useful for development of functional indicators to visualize second
      messenger molecules and activation of signaling components in living cells.
      However, the design and construction of the functional indicators require careful
      optimization of their structure at the atomic level. Therefore, routine
      procedures for constructing FRET-based indicators currently include the
      adjustment of the linker length between the FPs and the sensor domain and
      relative dipole orientation of the FP chromophore. Here we report that, in
      addition to these techniques, optimization of the dimerization interface of
      Aequorea FPs is essential to achieve the highest possible dynamic range of signal
      change by FRET-based indicators. We performed spectroscopic analyses of various
      indicators (cameleon, TN-XL, and ATeam) and their variants. We chose variants
      containing mutant FPs with different dimerization properties, i.e., no, weak, or
      enhanced dimerization of the donor or acceptor FP. Our findings revealed that the
      FPs that dimerized weakly yielded high-performance FRET-based indicators with the
      greatest dynamic range.

PMID- 20047339
TI  - Temporal proteomic analysis of human cervicovaginal fluid with impending term
      labor.

PMID- 20047340
TI  - Single-step procedure for the isolation of proteins at near-native conditions
      from mammalian tissue for proteomic analysis on antibody microarrays.
AB  - The process of extracting comprehensive proteome representations is a crucial
      step for many proteomic studies. While antibody microarrays are an evolving and
      promising methodology in proteomics, the issue of protein extraction from tissues
      for this kind of analysis has never been addressed. Here, we describe a single
      step extraction buffer for the isolation of proteins from mammalian tissues under
      native conditions in an effective and reproducible manner. Protein was extracted
      from cell lines BxPC-3 and SU.86.86, rat organs (pancreas, liver, heart and lung)
      and human pancreatic cancer tissues using several buffer systems that contained
      individual nonionic or zwitterionic detergents in comparison to commercial
      extraction buffers. Also, detergent combinations were used that included at least
      one polymeric phenylethylene glycol, a long-chain amidosulfobetaine, cholate and
      a zwitterionic detergent. Extracts were analyzed for protein quantity and
      quality. The detergent cocktails exhibited superior extraction capacity.
      Additionally, they demonstrated a substantially higher recovery of membrane and
      compartmental proteins as well as much better preservation of protein
      functionality. Also, they did not interfere with subsequent analysis steps such
      as labeling. In Western blot and antibody microarray assays, they outperformed
      the other buffer systems, indicating that they should also be useful for other
      types of proteomic studies.

PMID- 20047341
TI  - Photoinduced fluorescent cross-linking of 5-chloro- and 5-fluoro-4-thiouridines
      with thymidine.
AB  - Two highly fluorescent, thermally stable diastereomeric photoadducts, 3a,b, are
      formed when either 5-chloro-4-thiouridine, 1, or 5-fluoro-4-thiouridine, 2, are
      photoexcited with 366 nm UV light in the presence of thymidine (T). 5-Fluoro-4
      thiouridine, 2, exhibits photoreactivity much higher than that of the 5-chloro
      derivative 1. In both cases the photoreaction is very clean, leading to highly
      eficient conversion of the 5-halogeno-4-thiouridine (1, 2) and T to photoadducts
      3a,b. The identity and structure of 3a was confirmed using mass spectrometry and
      2-D NMR. The epimeric relationship of 3a,b was established by UV circular
      dichroism spectroscopy. The geometry of the fluorescent photoadduct is consistent
      with formation of an interstrand cross-link in a DNA duplex if 1 or 2 is flanked
      by T in an opposite strand.

PMID- 20047342
TI  - Diastereoselective Diels-Alder reactions with an allenyl-containing spiro-amido
      chiral auxiliary.
AB  - A novel allenyl-containing 1,3-spiro-amido alcohol auxiliary has been prepared
      and used in a variety of diastereoselective Diels-Alder reactions providing
      exclusively endo adducts with diastereomeric ratios ranging from 2:1 to >99:1.

PMID- 20047343
TI  - A divergent strategy for attaching polypyridyl ligands to peptides.
AB  - A divergent method for incorporating polypyridyl ligands into peptides is
      reported. Three N-Fmoc unnatural amino acids (1-3) that contain varying linkers
      between the alpha-carbon and a 2-(hydroxymethyl)pyridyl group were synthesized in
      enantioenriched form. These amino acids were used as anchors for incorporating
      multidentate ligands onto a peptide chain in a site-specific fashion. Multiple
      peptide-ligand conjugates were synthesized from single precursors by solution- or
      solid-phase methods. Peptides containing more than one metal-binding unit can be
      produced by this method.

PMID- 20047344
TI  - Effective purification of single-walled carbon nanotubes with reversible
      noncovalent functionalization.
AB  - An effective purification method for single-walled carbon nanotubes (SWNTs) based
      on a combination of oxidative acid treatment and reversible noncovalent
      functionalization with 1-pyreneacetic acid is reported. The functionalization was
      selective toward the nanotubes, allowing a nearly complete removal of residual
      metal catalysts and carbonaceous impurities. The resulting highly pure SWNTs
      remained solvent-dispersible, a valuable feature to potential applications that
      require solvent-based processing. The functionalization agent could be recovered
      quantitatively and reused. Effects of the purification process on the composition
      and properties of the nanotube sample were evaluated.

PMID- 20047345
TI  - Colorimetric sensing of alpha-amino acids and its application for the "label
      free" detection of protease.
AB  - A new indirect approach to explore sensitive colorimetric sensors toward alpha
      amino acids is proposed: the pink solution of 1 and copper ions changed to
      colorless immediately upon the addition of alpha-amino acids. As the hydrolysis
      of bovine serum albumin (BSA) with the aid of trypsin produces alpha-amino acids,
      the complex of 1/Cu(2+)/BSA could act as a label-free, sensitive, selective
      sensor toward trypsin. The detection process could be visually observed by naked
      eyes.

PMID- 20047346
TI  - Sleep research and sleep medicine.

PMID- 20047347
TI  - Does effective management of sleep disorders improve pain symptoms?
AB  - Co-morbid insomnia is a much more frequent problem than primary insomnia. In co
      morbid insomnia, management of the underlying disease can improve sleep
      difficulty. Conversely, treating the sleep disorder may also improve the co
      morbid condition. For example, patients with painful chronic illnesses are more
      likely to experience sleep disturbance than patients with non-painful illnesses.
      Moreover, there is evidence that insomnia further exacerbates pain in these
      illnesses. This suggests that a reciprocal relationship exists between pain and
      sleep, and that intervention targeted primarily at insomnia may improve pain.
      Treatment options for sleep disorders in the context of pain that have been
      assessed include cognitive behavioural therapy for insomnia and various
      pharmacological therapies. In randomized clinical trials, cognitive behavioural
      therapy significantly improved insomnia secondary to chronic pain compared with
      control therapy, but pain was only improved in patients in whom it was associated
      with pain disorders other than fibromyalgia. Of the pharmacological agents
      studied (zopiclone, zolpidem and triazolam), only triazolam improved both sleep
      and pain to a greater extent than placebo. Overall, clinical data supporting a
      cause-effect relationship between insomnia and pain are preliminary and are
      limited to several small trials. Further investigation is required to clarify the
      extent of the link between insomnia and pain and whether successfully managing
      insomnia secondary to pain improves pain symptoms. Areas of particular interest
      include investigation of the effect of sleep agents on analgesia and the effect
      of analgesics on sleep.

PMID- 20047348
TI  - Do sleep disorders and associated treatments impact glucose metabolism?
AB  - Over the past decade substantial evidence has accumulated implicating disorders
      of sleep in the pathogenesis of various metabolic abnormalities. This review,
      which is based on workshop discussions that took place at the 6th annual meeting
      of the International Sleep Disorders Forum: The Art of Good Sleep 2008 and a
      systematic literature search, provides a critical analysis of the available
      evidence implicating sleep disorders such as obstructive sleep apnoea (OSA),
      insomnia, short or long-term sleep duration and restless legs syndrome as
      potential risk factors for insulin resistance, glucose intolerance, type 2
      diabetes mellitus and the metabolic syndrome. The review also highlights the
      evidence on whether treatment of specific sleep disorders can decrease metabolic
      risk. In total, 83 published reports were selected for inclusion. Although
      several studies show clear associations between sleep disorders and altered
      glucose metabolism, causal effects and the underlying pathophysiological
      mechanisms involved have not been fully elucidated. OSA appears to have the
      strongest association with insulin resistance, glucose intolerance, type 2
      diabetes and the metabolic syndrome. There are, however, limited data supporting
      the hypothesis that effective treatment of sleep disorders, including OSA, has a
      favourable effect on glucose metabolism. Large randomized trials are thus
      required to address whether improvement of sleep quality and quantity can curtail
      excess metabolic risk. Research is also required to elucidate the mechanisms
      involved and to determine whether the effects of treatment for sleep disorders on
      glucose metabolism are dependent on the specific patient factors, the type of
      disorder and the duration of metabolic dysfunction. In conclusion, there is
      limited evidence on whether sleep disorders alter glucose metabolism and whether
      treatment can reduce the excess metabolic risk.

PMID- 20047349
TI  - Does effective management of sleep disorders reduce cancer-related fatigue?
AB  - Cancer and cancer therapy are often associated with symptoms such as fatigue and
      sleep disturbances, before, during and after therapy. These symptoms of fatigue
      and poor sleep often occur in parallel having a significant impact on the
      physical functioning of patients with cancer. A strong correlation between cancer
      related fatigue (CRF) and sleep has been observed in several studies, suggesting
      that they may be reciprocally related. The co-clustering of these symptoms
      suggests that they may have similar underlying aetiology and that treatments
      targeting either symptom may positively affect the other. Studies examining these
      clusters have shown that these symptoms often co-vary together. The potential
      mechanisms that link the relationship between insomnia and CRF are intriguing but
      require further investigation. Despite the high prevalence of insomnia and the
      often bidirectional relationship between poor sleep and fatigue, there are
      limited data to support the use of sleep management interventions as a means to
      reduce fatigue in patients with cancer. Assessment of the available evidence
      across trials is complicated by different study designs, patient selection
      criteria, stage of cancer treatment and by the nature of the interventions
      studied. Improvements from baseline in both sleep parameters and CRF have been
      documented in a limited number of studies, including two randomized-controlled
      trials using cognitive behavioural therapy for insomnia (CBT-I). In contrast, the
      efficacy of pharmacological therapies in reducing both insomnia and CRF is
      largely lacking. Clearly, treating clinically significant insomnia is likely to
      have benefits for the patient with cancer and for those who are recovering from
      cancer. In particular, pharmacotherapies for insomnia, singly or in combination
      with CBT-I, should be evaluated in multicentre randomized clinical trials to
      examine their efficacy in improving sleep quality and reducing associated CRF.

PMID- 20047350
TI  - Does effective management of sleep disorders reduce depressive symptoms and the
      risk of depression?
AB  - The link between co-morbid insomnia and depression has been demonstrated in
      numerous groups. Insomnia has been associated with: (1) an increased risk of
      developing subsequent depression; (2) an increased duration of established
      depression; and (3) relapse following treatment for depression. In addition,
      specific insomnia symptoms, such as nocturnal awakening with difficulty resuming
      sleep, are more strongly associated with depression than classic symptoms of
      insomnia. Participants of a workshop, held at the 6th annual meeting of The
      International Sleep Disorders Forum: The Art of Good Sleep in 2008, evaluated
      whether the effective management of sleep disorders could reduce both concurrent
      depressive symptoms and the risk of developing subsequent depression. Following
      the workshop, a targeted literature review was conducted. Initial evidence
      demonstrated that in patients with insomnia and co-morbid depression either
      pharmacological treatment of insomnia or psychological treatment in the form of
      cognitive behavioural therapy for insomnia improved both insomnia and depressive
      symptoms. Although these appeared to be promising treatment strategies, however,
      of the 27 identified treatment studies, only one large well-designed randomized
      controlled trial comparing the efficacy of eszopiclone plus fluoxetine with
      placebo plus fluoxetine demonstrated unequivocal evidence that improvements in
      insomnia symptoms conferred additive benefits on depressive outcomes. In
      addition, it was unclear whether any differences exist in efficacy between
      sedating versus non-sedating pharmacotherapies for insomnia in this patient
      group. Further studies of sufficient sample size and duration are needed to
      evaluate combinations of pharmacological (either sedating or non-sedating) and
      psychological interventions in co-morbid insomnia and depression. This article
      reviews the level of evidence, recommendations and areas of particular interest
      for further study and discussion arising from this workshop.

PMID- 20047351
TI  - Does effective management of sleep disorders reduce substance dependence?
AB  - Insomnia is often associated with substance dependence, with evidence suggesting
      that individuals seeking medical attention for sleep complaints are more likely
      to have drug or alcohol abuse problems than the general population. Disturbed
      sleep is associated with the abuse of a variety of drugs, with patients dependent
      on nicotine, alcohol and illicit drugs all reporting poor sleep. In addition,
      withdrawal from nicotine, alcohol and drugs of abuse is also associated with
      insomnia, and this may result in an increased risk of relapse if the sleep
      problems remain unresolved. Although studies suggest that the majority of
      pharmacological and behavioural interventions for insomnia are effective in
      treating sleep disturbances in dependent patients undergoing short-term drug
      withdrawal and short and long-term alcohol withdrawal, several questions remain
      unanswered. For example, little is known about the risk of relapse in abstinent
      drug-dependent patients experiencing withdrawal-related insomnia, the effect of
      insomnia treatment on nicotine withdrawal, or whether insomnia interventions
      prevent relapse. Participants of a workshop, held at the 6th annual meeting of
      The International Sleep Disorders Forum: The Art of Good Sleep in 2008, evaluated
      whether the effective management of sleep disorders could reduce substance
      dependence and the risk of relapse. Following the workshop a targeted literature
      review was conducted addressing this question. Data from this review that either
      pharmacological or cognitive behavioural treatment of insomnia could reduce the
      risk of relapse in substance dependence were substantially lacking. Further
      research is therefore required to increase our understanding of the impact of
      insomnia on patients with substance dependence.

PMID- 20047353
TI  - Primary care for patient complexity, not only disease.
AB  - Primary care is increasingly geared toward standardized care and decision-making
      for common chronic conditions, combinations of medical and mental health
      conditions, and the behavioral aspects of care for those conditions. Yet even
      with well-integrated team-based care for health conditions in place, some
      patients do not engage or respond as well as clinicians would wish or predict.
      This troubles patients and clinicians alike and is often chalked up informally to
      "patient complexity." Indeed, every clinician has encountered complex patients
      and reacted with "Oh my gosh"-but not necessarily with a patterned vocabulary for
      exactly how the patient is complex and what to do about it. Based on work in the
      Netherlands, patient complexity is defined here as interference with standard
      care and decision-making by symptom severity or impairments, diagnostic
      uncertainty, difficulty engaging care, lack of social safety or participation,
      disorganization of care, and difficult patient-clinician relationships. A
      blueprint for patient-centered medical home must address patient complexity by
      promoting the interplay of usual care for conditions and individualized attention
      to patient-specific sources of complexity-across whatever diseases and conditions
      the patient may have.

PMID- 20047352
TI  - Can improving sleep influence sleep-disordered breathing?
AB  - Sleep-disordered breathing (SDB) encompasses a group of disorders that include
      obstructive sleep apnoea (OSA), central sleep apnoea (CSA) and nocturnal
      hypoventilation. SDB commonly coexists with sleep disorders such as insomnia and
      restless legs syndrome, and sleep deprivation has been shown to play a role in
      the pathogenesis of SDB. Participants of a workshop, held at the 6th annual
      meeting of The International Sleep Disorders Forum: The Art of Good Sleep in
      2008, evaluated whether the effective management of sleep disorders could result
      in a reduction in SDB. Following the workshop, a critical review of the
      literature in the field of sleep and SDB was conducted in order to assess the
      impact of improving sleep on SDB, and to determine whether measures taken to
      improve sleep result in a subsequent improvement in SDB. Results showed that
      studies evaluating the influence of improved sleep on respiratory abnormalities
      in patients with SDB are lacking. Studies in patients with OSA, with or without
      obesity-hypoventilation syndrome, show that therapy with continuous positive
      airways pressure and non-invasive ventilation improves sleep parameters with
      beneficial effects on SDB. Studies involving small numbers of patients have shown
      that the antidepressants fluoxetine and mirtazapine produce improvements in sleep
      parameters and the apnoea-hypopnoea index, and that acetazolamide may improve
      CSA. The benzodiazepines flurazepam, temazepam and nitrazepam, the hypnotic
      zolpidem, the melatonin receptor agonist ramelteon and gamma-hydroxybutyrate have
      all been shown to improve sleep, but are not associated with reductions or
      worsening in SDB. It is clear that there is a distinct knowledge gap with regard
      to the benefit of improving sleep disturbances for subsequent improvements in
      SDB. Randomized controlled clinical trials investigating the effect of
      pharmacological and non-pharmacological improvement of sleep disorders focusing
      on whether there is improvement in coexisting OSA/SDB are clearly needed.
      Furthermore, well-designed clinical trials investigating the role of hypnotic
      agents in improving SDB in certain phenotypes will enable the development of
      treatment recommendations for primary care physicians managing these patients in
      routine clinical practice.

PMID- 20047354
TI  - Managing childhood chronic illness: parent perspectives and implications for
      parent-provider relationships.
AB  - When children have special health care needs, parents assume the roles of care
      coordinator, medical expert, and systems advocate as well as their typical
      parenting roles. They face many challenges in managing their child's chronic
      condition in the context of everyday life. Health care providers are uniquely
      positioned to assist parents in meeting those challenges and to promote parent
      competency and confidence in their child's care. The data for this analysis were
      collected during classes for parents of children with chronic conditions who took
      part in a randomized controlled study of a curriculum's effectiveness. During
      facilitated discussions, parents discussed challenges they faced and generated
      strategies they found helpful. Qualitative data analysis revealed dominant themes
      across subject areas. Challenges included social isolation, strained
      relationships and ongoing frustrations with health care and educational systems.
      Helpful strategies focused on being prepared, connecting with peers, becoming an
      advocate, developing partnerships and caring for one's self. Implications for
      health care providers include: understanding common challenges parents face;
      promoting parent-to-parent connections; and building partnerships with parents
      and their children with special needs.

PMID- 20047355
TI  - Stress among fathers of young children with type 1 diabetes.
AB  - Although fathers' stress has been shown to have important implications for
      children's health and well-being, few studies of children with Type 1 diabetes
      have considered paternal parenting stress. The current study contributes to the
      literature by exploring correlates of fathers' pediatric parenting stress in a
      sample of young children with Type 1 diabetes. Forty-three fathers of children 2
      6 years old with Type 1 diabetes completed self-report questionnaires examining
      pediatric parenting stress, child behavior, participation in diabetes management
      tasks, and parental psychological resources. Results of multiple regression show
      that fathers' pediatric parenting stress is positively associated with state
      anxiety and mother-reported difficult child behavior. These findings suggest that
      fathers may experience parenting stress differently than mothers, and that their
      experiences may have implications not only for their own level of anxiety, but
      also for their children's behavior.

PMID- 20047356
TI  - Maternal fatigue and its relationship to the caregiving environment.
AB  - For women with an autoimmune illness, fatigue can be a debilitating symptom that
      impacts many aspects of their life. There is scant research on maternal fatigue
      and its impact on the caregiving environment for either well women or women with
      chronic illnesses. The objective of this study was to examine the role maternal
      fatigue played in the caregiving environment, specifically in the mother's
      experience of the daily hassles of parenting, the discipline style she employed,
      and how she monitored her child's whereabouts. Two-hundred sixty-two mothers
      participated in this study: 103 mothers with multiple sclerosis (MS), 68 mothers
      with rheumatoid arthritis (RA), and a comparison group of 91 well mothers.
      Mothers completed questionnaires assessing their self-reported levels of fatigue,
      depression, quality and quantity of sleep, parenting daily hassles, discipline
      styles, and monitoring. After sleep, depression, and number of children were
      controlled for, fatigue explained additional variance in predicting monitoring
      for all three groups of mothers. Fatigue was also a significant predictor of
      parenting daily hassles for both well mothers and mothers with RA, but not for
      mothers with MS. For mothers with MS, it was the covariates (i.e., the number of
      children in the family and sleep quality and quantity) that were predictive of
      parenting daily hassles. Several explanations for mothers with MS not being as
      influenced by fatigue are discussed.

PMID- 20047357
TI  - Barriers and facilitators of adolescent behavioral health in primary care:
      Perceptions of primary care providers.
AB  - Several major policy reports describe the central role of primary care in
      improving the delivery of behavioral health care services to children and
      adolescents. Although primary care providers are uniquely positioned to provide
      these services, numerous obstacles hinder the integration of these services,
      including time, clinic management and organization issues, training, and
      resources. Although many of these obstacles have been described in the
      literature, few studies have investigated these issues from the first-person
      perspective of front-line providers. The purpose of this study, therefore, is to
      provide an in-depth description of primary care providers' attitudes and
      perceptions of adolescent behavioral health care across a diversity of primary
      care settings (i.e., Federally Qualified Health Center [FQHC], FQHC-Look Alike,
      school-based, military). Sixteen focus groups were conducted at 5 primary care
      clinics. Thematic analysis was used to analyze the focus group data. Obstacles to
      integration are presented as well as strategies to overcome these challenges,
      using training and education, working groups, and community collaboratives.

PMID- 20047358
TI  - Family-centered maternity care for deaf refugees: the patient-centered medical
      home in action.
AB  - The intersection of 2 underserved populations-refugees and deaf individuals
      presents novel challenges to health care systems and has not been described
      previously. A patient-centered medical home (PCMH) is uniquely equipped to
      provide outstanding primary care to disadvantaged groups. As an illustrative case
      study, we present our experience applying principles of the PCMH to address an
      extremely challenging clinical situation: providing high-quality maternity care
      to a recently immigrated Vietnamese refugee couple lacking formal language
      skills. We describe how enhanced access, continuity, coordination, and cultural
      appropriateness can facilitate favorable outcomes in even daunting circumstances.
      By collaborating with multiple interpreters, the health center staff, and the
      extended family, we effectively mobilized an expanded system of care to ensure
      informed consent and shared decision making, ultimately culminating in a
      successful labor and vaginal delivery. Through organizational and individual
      commitment to the tenets of the PCMH, we demonstrate the particular strengths of
      family medicine training sites in caring for similar patients and families with
      complex cultural and linguistic barriers to care.

PMID- 20047363
TI  - Exposure to nitrogen dioxide is not associated with vascular dysfunction in man.
AB  - BACKGROUND: Exposure to air pollution is associated with increased
      cardiorespiratory morbidity and mortality. It is unclear whether these effects
      are mediated through combustion-derived particulate matter or gaseous components,
      such as nitrogen dioxide. OBJECTIVES: To investigate the effect of nitrogen
      dioxide exposure on vascular vasomotor and six fibrinolytic functions. METHODS:
      Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered
      air for 1 h during intermittent exercise in a randomized double-blind crossover
      study. Bilateral forearm blood flow and fibrinolytic markers were measured before
      and during unilateral intrabrachial infusion of bradykinin (100-1000 pmol/min),
      acetylcholine (5-20 microg/min), sodium nitroprusside (2-8 microg/min), and
      verapamil (10-100 microg/min) 4 h after the exposure. Lung function was
      determined before and after the exposure, and exhaled nitric oxide at baseline
      and 1 and 4 h after the exposure. RESULTS: There were no differences in resting
      forearm blood flow after either exposure. There was a dose-dependent increase in
      forearm blood flow with all vasodilators but this was similar after either
      exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose
      dependent increase in plasma tissue-plasminogen activator, but again there was no
      difference between the exposures. There were no changes in lung function or
      exhaled nitric oxide following either exposure. CONCLUSION: Inhalation of
      nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function.
      Nitrogen dioxide does not appear to be a major arbiter of the adverse
      cardiovascular effects of air pollution.

PMID- 20047364
TI  - The impact of increasing neurological disability of multiple sclerosis on health
      utilities: a systematic review of the literature.
AB  - BACKGROUND: Multiple sclerosis (MS) is a debilitating disease, accompanied by
      neurological symptoms of varying severity. Utilities are a key summary index
      measure used in assessing health-related quality of life in individuals with MS.
      OBJECTIVES: To provide a systematic review of the literature on utilities of
      relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients and to
      review changes in utilities associated with the increasing neurological
      disability of different stages of MS, as measured by the Expanded Disability
      Status Scale (EDSS). METHODS: Employing pre-defined search terms and
      inclusion/exclusion criteria, systematic searches of the literature were
      conducted in EMBASE, MEDLINE, PsycINFO, the Health Economic Evaluation Database
      (HEED), and the NHS Economic Evaluations Database (NHS/EED). Proceedings for the
      International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the
      European Society for Treatment and Research in MS (ECTRIMS), the American Society
      for Treatment and Research in MS (ACTRIMS), and the Latin American Society for
      Treatment and Research in MS (LACTRIMS) were reviewed in addition to the UK
      National Institute for Health and Clinical Excellence website and the table of
      contents of PharmacoEconomics and Value in Health. RESULTS: This review
      identified 18 studies reporting utilities associated with health states of MS.
      Utilities ranged from 0.80 to 0.92 for patients with an EDSS score of 1, from
      0.49 to 0.71 for patients with an EDSS score of 3, from 0.39 to 0.54 for patients
      with an EDSS score of 6.5, and from -0.19 to 0.1 for patients with an EDSS score
      of 9. LIMITATIONS: Several of the studies reviewed relied on data from patient
      organizations, which may not be fully representative of the general patient
      populations. Additionally, the majority of the studies relied on retrospective
      data collection. CONCLUSIONS: Utilities decrease substantially with increasing
      neurological disability. Cross-country differences are minimal with utility
      scores following a similar pattern across countries for patients at similar
      disease severity levels. This consistency in findings is noteworthy, as there is
      a reliable evidence base for selecting utility values for economic evaluation
      analyses. However, more research is needed to explore potential differences in
      utilities between RRMS and SPMS patients.

PMID- 20047365
TI  - The economics of upper gastrointestinal bleeding in a US managed-care setting: a
      retrospective, claims-based analysis.
AB  - OBJECTIVE: To assess 12-month healthcare resource utilization and costs
      associated with upper gastrointestinal (UGI) bleeding events. METHODS: Patients
      hospitalized with a UGI bleeding event were identified in US national health-plan
      claims data (1999-2003) and propensity matched to control patients without UGI
      bleeding in the same health plan. Matching criteria included age, gender, index
      date, Charlson Comorbidity Index score, geographic region, and prior medical
      utilization. RESULTS: A total of 9,033 UGI-bleed patients and 579,018 control
      patients met the inclusion criteria, yielding 4,651 matched pairs. After
      matching, differences between the UGI bleed and general population cohorts
      remained for office visits, ER visits, and ER costs during the 6-month baseline
      period prior to the index date. During the 12 months following the index date,
      both UGI-related healthcare utilization and total healthcare, medical, and
      pharmacy costs incurred by the UGI-bleed cohort were significantly greater (p<
      0.0001) than those incurred by the general population cohort (mean of $20,405 vs.
      3,652), even after excluding the initial hospitalization costs (mean of $11,228
      vs. 3,652). Costs were primarily due to inpatient hospitalizations (mean of
      $13,059 for the UGI-bleed cohort vs. $729 for the general population cohort) and
      ambulatory services (mean of $4,037 for the UGI-bleed cohort vs. $1,537 for the
      general population cohort). Sixteen percent of the UGI-bleed cohort had a GI
      related hospitalization, and about 40% of total costs occurred after the initial
      hospitalization. CONCLUSIONS: Patients with UGI bleeds experienced significantly
      higher (p< 0.0001) 12-month health-resource utilization and costs than patients
      without UGI bleeds. This study provides empirical evidence of the long-term
      economic burden associated with UGI bleeding. Interpretation of the results
      should take into account the lack of available information in claims data that
      could have an effect on study outcomes, such as particular clinical and disease
      specific parameters that are not mitigated by propensity score and comorbidity
      index matching. In addition, this study is limited by the intensive demographic
      matching that was done between the two cohorts, which may have eliminated the
      sickest UGI patients and the healthiest general health-plan population patients.

PMID- 20047453
TI  - Room for improvement: mixed portrayal of young people with mental illness on
      Australian television news.
AB  - OBJECTIVE: The aim of the present study was to review television news depiction
      of mental illness in children and adolescents to test the hypothesis that
      positive portrayals of adults with mental illness also apply to young people.
      METHODS: Content and frame analysis of first-person depictions and overall news
      angle was carried out to determine whether depictions were positive, neutral or
      negative. RESULTS: The media portrayal of young people with mental illnesses was
      mixed. Overall, 10 items (29%) of news angles were positive, 13 items (37%)
      neutral and nine items (26%) negative. Positive themes were significantly less
      frequent for young people compared to adults (10 items, 29% compared to 151
      items, 66%), and negative themes were more frequent (nine items, 26% vs 21 items,
      9%). First-person depictions, however, were similar for young people and adults
      (24 items, 69% vs 150 items, 66%). An anti-medication sub-theme was notable.
      CONCLUSIONS: Overall the portrayal of young people with mental illnesses on
      television news is not as positive as that for adults. Similar to adults,
      however, first-person depictions resulted in a more positive representation of
      young people. Fewer first-person depictions in combination with an anti
      medication theme and historically less access to appropriate services for young
      people may have contributed to the less positive results for young people with
      mental illnesses.

PMID- 20047454
TI  - Pharmacological management in children and adolescents with pervasive
      developmental disorder.
AB  - OBJECTIVE: Pervasive developmental disorder (PDD) is associated with emotional
      and behavioural problems. There is no pharmacological cure for PDD, but some
      comorbidities and dysfunctional behaviours in PDD can be managed
      pharmacologically. The aim of the present study was to provide a better
      understanding of the efficacy and limitations in the currently available agents.
      METHODS: Electronic literature searches were conducted from the following
      sources: MEDLINE, Cochrane Library, PSYARTICLES and PsycINFO. Search terms
      included, but were not limited to, 'autism', 'PDD', 'autism spectrum disorder'
      ('ASD'), and 'pharmacological management'. RESULTS: A range of pharmacological
      agents are available for the management of various dysfunctional symptoms in PDD.
      Broadly speaking, these agents help in the management of repetitive stereotyped
      behaviours, anxiety, aggression/irritability/self-injurious behaviour,
      hyperactivity/inattention and in sleep. CONCLUSIONS: There is a paucity of
      systemic, well-conducted trials on the use of pharmacological agents in the
      management of PDD, and more research in this area is warranted.

PMID- 20047457
TI  - Proteases from psychrotrophs: an overview.
AB  - Proteases are hydrolytic enzymes which catalyze the total hydrolysis of proteins
      in to amino acids. Although proteolytic enzymes can be obtained from animals and
      plants but microorganisms are the preferred source for industrial applications in
      view of scientific and economical advantage. Among various groups of microbes,
      psychrotrophs are ideal candidates for enzymes production keeping in mind that
      enzymes active at low temperature and stable under alkaline condition, in
      presence of oxidants and detergents are in large demand as laundry additive. The
      proteases from psychrotrophs also find application in environmental
      bioremediation, food and molecular biology. During the previous two decades,
      proteases from psychrotrophs have received increased attention because of their
      wide range of applications, but the full potential of psychrotrophic proteases
      has not been exploited. This review focuses attention on the present status of
      knowledge on the production, optimization, molecular characteristics,
      applications, substrate specificity, and crystal structure of psychrotrophic
      proteases. The review will help in making strategies for exploitation of
      psychrotrophic protease resources and improvement of enzymes to obtain more
      robust proteases of industrial and biotechnological significance.

PMID- 20047458
TI  - The peptide that binds: a systematic review of oxytocin and its prosocial effects
      in humans.
AB  - Oxytocin is a neuropeptide involved in a wide variety of social behaviors in
      diverse species. Recent research on its effects in humans has generated an
      arresting picture of its role in the dynamic function of the social brain. This
      review presents a broad overview of this uniquely social peptide, with a
      particular focus on extant studies of its effects in humans. After a short
      discussion of the evolutionary history of the oxytocin system, critical aspects
      of its peripheral and central physiology, and several salient technical issues
      surrounding human oxytocin research, a systematic review of studies of the
      effects of intranasal oxytocin in humans is presented. These effects include
      alterations in social decision making, processing of social stimuli, certain
      uniquely social behaviors (e.g., eye contact), and social memory. Oxytocin's
      prosocial influence is then framed by an evolutionary perspective on its role in
      mammalian social bonding and attachment. Finally, limitations in current human
      oxytocin research and oxytocin's potential therapeutic applications are
      discussed. Key conclusions are (1) human research with intranasal oxytocin has
      uniquely enhanced our understanding of the microstructure and function of the
      human social brain, and (2) the oxytocin system is a promising target for
      therapeutic interventions in a variety of conditions, especially those
      characterized by anxiety and aberrations in social function.

PMID- 20047459
TI  - Hallucinations in nonpsychotic disorders: toward a differential diagnosis of
      "hearing voices".
AB  - While auditory hallucinations (AH) are prototypic psychotic symptoms whose
      clinical presence is often equated with a psychotic disorder, they are commonly
      found among those without mental illness as well as those with nonpsychotic
      disorders not typically associated with hallucinations in DSM-IV. This
      incongruity presents a significant challenge for clinical work and efforts to
      revise the next iteration of the DSM. Auditory hallucinations found among
      "normal" people suggest that either AH are not as pathologic as they are
      typically taken to be, or that less-than-hallucinatory experiences are routinely
      mischaracterized as AH. Such hallucinations in the context of conversion
      disorder, trauma, sensory deprivation, and certain cultural settings strengthen
      an association between AH and psychopathology but suggest limited diagnostic
      specificity and relevance. It may be useful to think of AH like coughs-common
      experiences that are often, but not always, symptoms of pathology associated with
      a larger illness. Although these issues have been known for many years, they are
      rarely discussed in American psychiatry and need to be addressed in future
      research and clinical work.

PMID- 20047461
TI  - Over the rainbow: a case of traumatic brain injury.

PMID- 20047460
TI  - The psychopharmacology algorithm project at the Harvard South Shore Program: an
      update on bipolar depression.
AB  - This updated version of the bipolar depression algorithm of the
      Psychopharmacology Algorithm Project at the Harvard South Shore Program aims to
      provide an organized, sequential, and evidence-supported approach for the
      treatment of that disorder. After initial evaluation and diagnosis, the
      psychiatrist should first assess whether there is an urgent indication for ECT.
      If ECT is not indicated, and the patient has psychotic symptoms, then an
      antipsychotic should be part of the medication regimen. Next, if the patient is
      not currently treated with mood stabilizers, there is a slight preference for
      lithium. If lithium is not effective or tolerated, treatment with quetiapine or
      lamotrigine should be initiated. If the patient is currently taking other mood
      stabilizers, their dosage should be optimized, and the clinician should consider
      adding or switching to lithium, quetiapine, or lamotrigine. Next, if the patient
      is not at especially high risk of mood destabilization, an antidepressant can be
      added in the bipolar depressed patient who has failed trials of lithium,
      quetiapine, and lamotrigine. Rapid-cycling depressed patients may require
      combinations of two or three mood stabilizers. ECT, along with other
      psychopharmacological options, could be reconsidered for the treatment of
      refractory bipolar depressed patients.

PMID- 20047464
TI  - Pisces and cancer: the stars align.

PMID- 20047462
TI  - A new role for endophenotypes in the GWAS era: functional characterization of
      risk variants.

PMID- 20047465
TI  - Identification of a heritable model of testicular germ cell tumor in the
      zebrafish.
AB  - Germ cell tumors (GCTs) affect infants, children, and adults and are the most
      common cancer type in young men. Progress in understanding the molecular basis of
      GCTs has been hampered by a lack of suitable animal models. Here we report the
      identification of a zebrafish model of highly penetrant, heritable testicular GCT
      isolated as part of a forward genetic screen for cancer susceptibility genes. The
      mutant line develops spontaneous testicular tumors at a median age of 7 months,
      and pedigree analysis indicates dominant inheritance of the GCT susceptibility
      trait. The zebrafish model exhibits disruption of testicular tissue architecture
      and the accumulation of primitive, spermatogonial-like cells with loss of
      spermatocytic differentiation. Radiation treatment leads to apoptosis of the
      tumor cells and tumor regression. The GCT-susceptible line can serve as a model
      for understanding the mechanisms regulating germ cells in normal development and
      disease and as a platform investigating new therapeutic approaches for GCTs.

PMID- 20047466
TI  - What a fish can learn from a mouse: principles and strategies for modeling human
      cancer in mice.
AB  - This review highlights the current techniques used to generate transgenic mouse
      models of cancer, with an emphasis on recent advances in the use of ubiquitous
      promoters, models that use Cre-loxP and Flip-FRT recombinase technology,
      inducible systems, RNAi to target genes, and transposon mutagenesis. A concluding
      section discusses new imaging systems that visualize tumor progression and the
      microenvironment in vivo. In this review, these techniques and strategies used in
      mouse models of cancer are highlighted, as they are pertinent and relevant to the
      development of zebrafish models of cancer.

PMID- 20047467
TI  - Zebrafish tumor assays: the state of transplantation.
AB  - Tumor transplant studies are important tools for studying cancer biology in a
      model organism. Transplantation is especially important for assaying tumor cell
      malignancy and migration capabilities, and is critical for identifying putative
      cancer stem cell populations. In this review, we discuss the current state of
      tumor transplantation studies performed in the zebrafish. We address several
      zebrafish-specific considerations for development of the transplant assay,
      including choosing recipient animals, transplant methods, and post-transplant
      observation. We also examine how the zebrafish is an advantageous model for
      transplantation, particularly with development of the translucent fish.
      Transplantation has already been critical for characterizing zebrafish models of
      leukemia, rhabdomyosarcoma, and melanoma. With further development of imaging
      techniques and other tools, zebrafish tumor transplantation will continue to
      contribute to our understanding of tumor cell biology.

PMID- 20047469
TI  - Global repression of cancer gene expression in a zebrafish model of melanoma is
      linked to epigenetic regulation.
AB  - We have established a model of melanoma progression in zebrafish through the
      generation of transgenic lines specifically expressing oncogenic human HRAS in
      the melanocytic lineage. In these tumors we have carried out quantitative
      expression analysis of several putative cancer genes, from known and predicted
      cancer gene lists. In particular, we analyzed 39 out of 101 putative cancer genes
      identified with a bioinformatics approach and selected for the low frequency of
      duplication and the high connectivity in protein networks. Data obtained by real
      time polymerase chain reaction analysis from zebrafish melanoma tissue shows that
      the expression of many cancer genes is downregulated in zebrafish melanomas,
      whereas only cell cycle genes are upregulated. To understand whether this trend
      is due to global repression of gene expression associated to a repressive
      chromatin state, we investigated whether changes of histone methylation were
      detectable in our melanoma model. We found substantial differences in the levels
      of H3K9me3, H4K20me2, H3K27me3, H3K4me3, and H3R2me2a immunostaining in melanoma
      tissue when compared with normal skin. Thus our analysis suggests that in our
      model, like in human melanoma, important changes occur to the methylation status
      of histones. Although the outcome of these changes is still unknown, they could
      be responsible for the global repression of gene expression through epigenetic
      regulation shown in this study.

PMID- 20047470
TI  - LIMK1 and LIMK2 are important for metastatic behavior and tumor cell-induced
      angiogenesis of pancreatic cancer cells.
AB  - The two LIM kinases (LIMKs) LIMK1 and LIMK2 are members of the PDZ/LIM family.
      These serine/threonine protein kinases are involved in actin cytoskeleton
      reorganization through phosphorylation and inactivation of ADF/cofilin. Different
      subcellular localizations of LIMK1 and LIMK2 suggest different functions. LIMK1
      is implicated in microtubule disassembly in endothelial- and cancer cells,
      whereas LIMK2 plays a role in cell cycle progression. To compare the role of the
      two LIMKs in cancer-related processes, we used a cell-based in vitro migration
      assay, as well as two zebrafish xenograft assays. We analyzed here the metastatic
      behavior and tumor cell-induced neovascularization of pancreatic cancer cells in
      which both LIMK genes were silenced by siRNAs. Both LIMK1 and LIMK2 single knock
      down led to a reduction of invasion and metastatic behavior in the zebrafish
      xenograft metastasis assay. Interestingly, the double knock down completely
      blocked invasion and formation of micrometastasis in vivo. Moreover, in the
      zebrafish xenograft angiogenesis assay, we observed a reduction of pancreatic
      cancer cell-induced angiogenesis for both the LIMK1 and LIMK2 knockdowns. Our
      results demonstrate similar functions for the two LIMKs in pancreatic cancer
      cells and suggest an important role for both LIMK1 and LIMK2 in tumor progression
      and metastasis formation.

PMID- 20047468
TI  - Zebrafish have a competent p53-dependent nucleotide excision repair pathway to
      resolve ultraviolet B-induced DNA damage in the skin.
AB  - Ultraviolet (UV) light is a primary environmental risk factor for melanoma, a
      deadly form of skin cancer derived from the pigmented cells called melanocytes.
      UVB irradiation causes DNA damage, mainly in the form of pyrimidine dimers (cis
      syn cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts),
      and organisms have developed complex multiprotein repair processes to cope with
      the DNA damage. Zebrafish is becoming an important model system to study the
      effects of UV light in animals, in part because the embryos are easily treated
      with UV irradiation, and the DNA damage repair pathways appear to be conserved in
      zebrafish and mammals. We are interested in exploring the effects of UV
      irradiation in young adult zebrafish, so that we can apply them to the study of
      gene-environment interactions in models of skin cancer. Using the Xiphophorus UV
      melanoma model as a starting point, we have developed a UV irradiation treatment
      chamber, and established UV treatment conditions at different ages of
      development. By translating the Xiphophorus UV treatment methodology to the
      zebrafish system, we show that the adult zebrafish skin is competent for
      nucleotide excision DNA damage repair, and that like in mammalian cells, UV
      treatment promotes phosphorylation of H2AX and a p53-dependent response. These
      studies provide the groundwork for exploring the role of UV light in melanoma
      development in zebrafish.

PMID- 20047471
TI  - Disease modeling in zebrafish: cancer and immune responses--a report on a
      workshop held in Spoleto, Italy, July 20-22, 2009.
AB  - The growing interest in using zebrafish for genetic and functional dissection of
      malignancy and infection was highlighted by the second international workshop on
      Zebrafish Models of Cancer and the Immune Response in Spoleto, Italy (July 20-22,
      2009). The overarching theme of the state-of-the-art reports featured the unique
      suitability of zebrafish for in vivo monitoring of fundamental biologic and
      pathologic processes. For example, in vivo imaging was employed for the first
      demonstration of direct development of hematopoietic stem cells from hemogenic
      epithelium and for visualization of T-cell homing and interaction with thymic
      epithelial cells. In addition, in vivo monitoring was instrumental for developing
      disease models of solid tumors, leukemia, and of inflammatory conditions, and for
      assessing the efficacy of small molecule drugs under physiologic and pathologic
      conditions. The success of zebrafish small molecule screens was underscored by
      the identification of prostaglandin E2 (PGE2) as an efficient inducer of stem
      cell expansion that led to the initiation of the first human trial on the
      efficacy of PGE2 in bone marrow transplantation. Further, zebrafish models of
      infectious diseases such as tuberculosis have been established that are now
      amenable to high-throughput in vivo drug screens, a much-needed development in
      the fight against drug-resistant microorganisms. The success of this workshop and
      the rapidly growing field of cancer and the immune response in zebrafish have
      spawned follow-up meetings in Boston (June 2010) and Edinburgh (2011).

PMID- 20047475
TI  - LGL leukemia and HTLV.
AB  - Samples were obtained from 53 large granular lymphocytic leukemia (LGLL) patients
      and 10,000 volunteer blood donors (VBD). Sera were screened in an HTLV-1 enzyme
      immunoassay (EIA) and further analyzed in peptide-specific Western blots (WB).
      DNAs were analyzed by HTLV-1, -2, -3, and -4-specific PCR. Forty four percent of
      LGLL patients vs. 0.12 % of VBD had anti-HTLV antibodies via EIA (p < 0.001). WB
      and PCR revealed that four LGLL patients (7.5%) vs. one VBD patient (0.01%) were
      infected with HTLV-2 (p < 0.001), suggesting an HTLV-2 etiology in a minority of
      cases. No LGLL patient was positive for HTLV-1, -3, or -4, whereas only one EIA
      positive VBD was positive for HTLV-1 and none for HTLV-3 or -4. The HTLV EIA
      positive, PCR-negative LGLL patients' sera reacted to epitopes within HTLV p24
      gag and gp21 env. Other then the PTLV/BLV viruses, human endogenous retroviral
      element HERV K10 was the only sequence homologous to these two HTLV peptides,
      raising the possibility of cross-reactivity. Although three LGLL patients (5.7%)
      vs. none of 110 VBD patients tested positive for antibodies to the homologous
      HERV K10 peptide (p = 0.03), the significance of the anti-HTLV seroreactivity
      observed in many LGLL patients remains unclear. Interestingly, out of 36 HTLV-1
      positive control subjects, 3 (8%) (p = 0.014) were positive for antibodies to
      HERV K10; all three had myelopathy. Out of 64 HTLV-2-positive control subjects 16
      (25%) (p = <0.001) were positive for HERV K10 antibodies, and 4 (6%) of these had
      myelopathy. Out of 22 subjects with either HTLV-1 or -2 myelopathy, 7 (31.8%)
      were positive for HERV K10 antibodies, and out of 72 HTLV-infected subjects
      without myelopathy, 12 (16.7%) were positive for anti-HERV K10 antibodies (p =
      0.11). The prevalence of anti-HERV K10 antibodies in these populations and the
      clinical implications thereof need to be pursued further.

PMID- 20047476
TI  - Pneumocystis infection: seeing beyond the tip of the iceberg.

PMID- 20047477
TI  - Emergence of resistance to azithromycin-atovaquone in immunocompromised patients
      with Babesia microti infection.
AB  - BACKGROUND: Babesiosis is an emerging tickborne malaria-like infection
      principally caused by Babesia microti. This infection typically resolves either
      spontaneously or after administration of a 7-10-day course of azithromycin plus
      atovaquone or clindamycin plus quinine. Although certain highly immunocompromised
      patients may respond suboptimally to these drug regimens, unlike the situation
      with malaria there has been no reported evidence that the cause of treatment
      failure is infection with drug-resistant strains of B. microti. METHODS:
      Emergence of drug resistance in B. microti was defined as the development of a
      microbiologic relapse (recurrent parasitemia or a marked increase in parasitemia)
      in association with both clinical and laboratory abnormalities indicative of
      active babesiosis in a patient after 28 days of uninterrupted antibabesia drug
      therapy and while still receiving treatment. RESULTS: The clinical case histories
      of 3 highly immunocompromised patients who received a subcurative course of
      azithromycin-atovaquone associated with the eventual development of resistance to
      this drug regimen are described. One of the 3 patients died of complications
      related to babesiosis. CONCLUSIONS: B. microti may become resistant to
      azithromycin-atovaquone during the treatment of babesiosis with this combined
      drug regimen in highly immunocompromised patients. Although research is needed to
      determine the optimal therapy for highly immunocompromised patients with
      babesiosis, reducing the level of immunosuppression when possible would appear to
      be a desirable strategy.

PMID- 20047478
TI  - Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over
      7 decades.
AB  - BACKGROUND: Pneumococcal infections have historically played a major role in
      terms of morbidity and mortality. We explored historical trends of invasive
      pneumococcal disease (IPD) and pneumococcal serotypes in a population exposed to
      limited antibiotic selective pressure and conjugate pneumococcal vaccination
      (PCV). METHODS: Retrospective cohort study based on nationwide laboratory
      surveillance data on IPD collected uninterruptedly in Denmark during 1938-2007.
      Changes in the reported incidence and trends of pneumococcal serotypes were
      explored using nonlinear regression analysis. RESULTS: There were 25,502 IPD
      cases included in our study. The median incidence of IPD increased from 2.8 cases
      per 100,000 population (interquartile range [IQR], 1.5-2.6) during the first 4
      decades to 15.7 cases per 100,000 population (IQR, 7-20.4) during the 1980s and
      1990s, mainly attributed to an increase in the number of bacteremia cases. The
      incidence of meningitis remained relatively stable, with a median of 1.3 cases
      per 100,000 population (IQR, 0.9-1.6). The proportions of serotypes/groups 4 and
      9 increased; the proportion of serotype 18C decreased; the proportions of
      serotypes 6, 7F, 14, and 23F remained stable; and serotype 2 nearly disappeared.
      Before the 1960s, serotypes 1, 2, 3, and 5 presented peaks every 2-3 years,
      becoming less frequent during the 1970s with peaks every 7-10 years. Between 20%
      and 90% of IPD in children <5 years were caused by PCV serotypes during the last
      4 decades. Cases of IPD caused by serotype 19A increased before introduction of
      PCV. Between 1993 and 2007, the level of resistance to macrolides and beta
      lactams was 6%. CONCLUSIONS: The epidemiology of IPD and single serotypes has
      constantly changed over the past 7 decades. PCV serotypes appeared to dominate
      the pneumococcal population.

PMID- 20047479
TI  - Elevations in mortality associated with weaning persist into the second year of
      life among uninfected children born to HIV-infected mothers.
AB  - BACKGROUND: Early weaning has been recommended to reduce postnatal human
      immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping
      breast-feeding at different ages for mortality of uninfected children born to HIV
      infected mothers. METHODS: During a trial of early weaning, 958 HIV-infected
      mothers and their infants were recruited and followed up from birth to 24 months
      postpartum in Lusaka, Zambia. One-half of the cohort was randomized to wean
      abruptly at 4 months, and the other half of the cohort was randomized to continue
      breast-feeding. We examined associations between uninfected child mortality and
      actual breast-feeding duration and investigated possible confounding and effect
      modification. RESULTS: The mortality rate among 749 uninfected children was 9.4%
      by 12 months of age and 13.6% by 24 months of age. Weaning during the interval
      encouraged by the protocol (4-5 months of age) was associated with a 2.03-fold
      increased risk of mortality (95% confidence interval [CI], 1.13-3.65), weaning at
      6-11 months of age was associated with a 3.54-fold increase (95% CI, 1.68-7.46),
      and weaning at 12-18 months of age was associated with a 4.22-fold increase (95%
      CI, 1.59-11.24). Significant effect modification was detected, such that risks
      associated with weaning were stronger among infants born to mothers with higher
      CD4(+) cell counts (>350 cells/microL). CONCLUSION: Shortening the normal
      duration of breast-feeding for uninfected children born to HIV-infected mothers
      living in low-resource settings is associated with significant increases in
      mortality extending into the second year of life. Intensive nutritional and
      counseling interventions reduce but do not eliminate this excess mortality.

PMID- 20047481
TI  - Therapy failure following selection of enfuvirtide-resistant HIV-1 in
      cerebrospinal fluid.
AB  - We report the selection of enfuvirtide-resistant human immunodeficiency virus
      type 1 in cerebrospinal fluid, resulting in subsequent loss of viral suppression
      in the plasma. This case report emphasizes the potential danger of low-level
      penetration of entry inhibitors into the central nervous system.

PMID- 20047482
TI  - Mortality among HIV-exposed infants: the first and final frontier.

PMID- 20047483
TI  - Preferential lower respiratory tract infection in swine-origin 2009 A(H1N1)
      influenza.
AB  - We report a case of 2009 influenza A(H1N1) virus infection in which virus was
      detected predominantly in specimens from the lower respiratory tract but was
      absent or at very low levels in nasopharyngeal swab samples. This presentation
      suggests that, in certain hosts or for particular variants of 2009 A(H1N1) virus,
      the lower respiratory tract may be the preferred site of infection.

PMID- 20047480
TI  - Clinical practice guidelines for the management of cryptococcal disease: 2010
      update by the infectious diseases society of america.
AB  - Cryptococcosis is a global invasive mycosis associated with significant morbidity
      and mortality. These guidelines for its management have been built on the
      previous Infectious Diseases Society of America guidelines from 2000 and include
      new sections. There is a discussion of the management of cryptococcal
      meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)
      infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected
      and nontransplant hosts. There are specific recommendations for other unique risk
      populations, such as children, pregnant women, persons in resource-limited
      environments, and those with Cryptococcus gattii infection. Recommendations for
      management also include other sites of infection, including strategies for
      pulmonary cryptococcosis. Emphasis has been placed on potential complications in
      management of cryptococcal infection, including increased intracranial pressure,
      immune reconstitution inflammatory syndrome (IRIS), drug resistance, and
      cryptococcomas. Three key management principles have been articulated: (1)
      induction therapy for meningoencephalitis using fungicidal regimens, such as a
      polyene and flucytosine, followed by suppressive regimens using fluconazole; (2)
      importance of early recognition and treatment of increased intracranial pressure
      and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in
      patients with renal impairment. Cryptococcosis remains a challenging management
      issue, with little new drug development or recent definitive studies. However, if
      the diagnosis is made early, if clinicians adhere to the basic principles of
      these guidelines, and if the underlying disease is controlled, then
      cryptococcosis can be managed successfully in the vast majority of patients.

PMID- 20047484
TI  - Epidemiology of Hepatitis B virus infection in a US cohort of HIV-infected
      individuals during the past 20 years.
AB  - BACKGROUND: The epidemiologic trends of hepatitis B virus (HBV) infection in
      human immunodeficiency virus (HIV)-infected patients over the past 20 years are
      largely unknown. METHODS: Prevalence and risk factors for HBV infection overall,
      at the time of HIV infection, and after HIV infection were examined in an ongoing
      observational HIV cohort study. Risk factors for HBV infection at the time of
      diagnosis of HIV infection were evaluated using logistic regression, and risk of
      incident HBV infection after diagnosis of HIV infection was evaluated using Cox
      proportional hazards models. RESULTS: Of the 2769 evaluable participants, 1078
      (39%) had HBV infection, of whom 117 (11%) had chronic HBV infection. The yearly
      cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995
      to 36% in 2008 (P < .001). The prevalence of HBV infection at the time of
      diagnosis of HIV infection decreased during 1989-2008 from 34% to 9% (P < .001).
      The incidence of HBV infection after diagnosis of HIV infection decreased from
      4.0 cases per 100 person-years during the pre-highly active antiretroviral
      therapy (HAART) era to 1.1 cases per 100 person-years during the HAART era (P <
      .001); however, this incidence remained unchanged during 2000-2008 (P = .49),
      with >20% of HBV infections occurring after HIV infection being chronic.
      Decreased risk of HBV infection after diagnosis of HIV infection was associated
      with higher CD4 cell count and the use of HBV-active HAART. Receipt of 1 dose of
      HBV vaccine was not associated with reduced risk of HBV infection after diagnosis
      of HIV infection. CONCLUSIONS: Although the burden of HBV infection overall is
      slowly decreasing among HIV-infected individuals, the persistent rate of HBV
      infection after diagnosis of HIV infection raises concern that more-effective
      prevention strategies may be needed to significantly reduce the prevalence of HBV
      infection in this patient population.

PMID- 20047485
TI  - Fungal infections in leukemia patients: how do we prevent and treat them?
AB  - Invasive fungal infections (IFIs) remain an important cause of morbidity and
      mortality in patients with acute or chronic leukemia. Advances in the
      pharmacotherapy of fungal infections and a shift in the epidemiological
      characteristics of fungal pathogens toward fluconazole-resistant Candida species
      and saprophytic molds have placed a greater emphasis on selection of broader
      spectrum agents for empirical therapy of IFIs in this high-risk population. Newer
      diagnostic modalities, such as the Aspergillus galactomannan test, the 1,3-beta-d
      glucan test, and polymerase chain reaction detection of fungal DNA, may
      facilitate the earlier diagnosis of IFIs, but their role in detecting
      breakthrough infection and their usefulness as a marker to withhold antifungal
      therapy in high-risk leukemia patients with IFI are less obvious, especially in
      patients who are receiving antifungal prophylaxis. Only 2 strategies have been
      shown in prospective studies to improve survival from mold infection in patients
      with acute myelogenous leukemia or myelodysplastic syndrome: (1) preemptive
      initiation of antifungal therapy at first sign of invasive aspergillosis on
      computed tomography (CT) scan and (2) antifungal prophylaxis with posaconazole.
      CT-guided treatment decisions are more complex in patients with advanced
      leukemia, however, because of concomitant infection or relapsing malignancy.
      Similarly, posaconazole is often not a viable prophylaxis or treatment option in
      patients with poor oral intake, gastrointestinal dysfunction, or possible drug
      interaction (eg, proton pump inhibitor prophylaxis in patients on high-dose
      glucocorticosteroids). As a result, the management of IFI in patients with
      leukemia demands an individualized treatment plan.

PMID- 20047486
TI  - Pneumocystis colonization in older adults and diagnostic yield of single versus
      paired noninvasive respiratory sampling.
AB  - The presence of Pneumocystis was assessed in oropharyngeal wash specimens from
      110 adults (median age, 76 years; age range, 69-95 years), 66 of whom had a
      paired nasal swab specimen. Pneumocystis jirovecii DNA was detected in 12.8% of
      oropharyngeal wash specimens, and the frequency increased to 21.5% in paired
      specimens. Pneumocystis colonization is prevalent in older adults. Double
      noninvasive sampling increases the diagnostic yield.

PMID- 20047487
TI  - Pneumocystis colonization is highly prevalent in the autopsied lungs of the
      general population.
AB  - BACKGROUND: Increasing reports of Pneumocystis DNA in noninvasive respiratory
      specimens from immunocompetent asymptomatic adults and the characteristic lung
      tropism of Pneumocystis suggest that asymptomatic pulmonary infections with
      Pneumocystis occur after primary infection. However, studies searching for
      Pneumocystis in the autopsied lungs of healthy immunocompetent adults have not
      met with success. METHODS: Lungs of people who died of violent causes (accidents,
      homicide, and suicide) and of nonviolent causes (diseases causing a rapid demise
      in the street) in Santiago, Chile-for whom an autopsy was legally required-were
      examined for Pneumocystis by nested polymerase chain reaction (PCR) DNA
      amplification of the mitochondrial large subunit ribosomal RNA-specific P.
      jirovecii gene and immunofluorescent microscopic analysis. Lung tissue
      concentration methods and analysis of approximately 3% of the weight of the right
      upper lobe (RUL) were needed to reach the sensitivity threshold of the assays.
      Individuals determined to be P. jirovecii negative after analysis of 3% of the
      RUL weight in the violent death group were confirmed to be negative by analyzing
      additional tissue, totaling 6%-7% of the RUL weight. RESULTS: P. jirovecii was
      identified by nested PCR in 50 (64.9%) of 77 individuals (34 [61.8%] of 55 in the
      violent death group and 15 [78.9%] of 19 in the nonviolent death group; P > .05)
      and additionally by microscopic analysis in all individuals who tested positive
      for P. jirovecii DNA in the violent death group. Analysis of tissue beyond 3.0%
      of the RUL weight for the individuals who tested negative yielded consistently
      negative results. CONCLUSIONS: A mild P. jirovecii pulmonary infection is
      prevalent in more than half of the general adult population. Our results
      strengthen the concept that immunocompetent adults develop frequent self-limited
      reinfections throughout life and participate in the circulation of P. jirovecii
      as an infective reservoir for susceptible individuals.

PMID- 20047489
TI  - A relational extension of the notion of motifs: application to the common 3D
      protein substructures searching problem.
AB  - The geometrical configurations of atoms in protein structures can be viewed as
      approximate relations among them. Then, finding similar common substructures
      within a set of protein structures belongs to a new class of problems that
      generalizes that of finding repeated motifs. The novelty lies in the addition of
      constraints on the motifs in terms of relations that must hold between pairs of
      positions of the motifs. We will hence denote them as relational motifs. For this
      class of problems, we present an algorithm that is a suitable extension of the
      KMR paradigm and, in particular, of the KMRC as it uses a degenerate alphabet.
      Our algorithm contains several improvements that become especially useful when-as
      it is required for relational motifs-the inference is made by partially
      overlapping shorter motifs, rather than concatenating them. The efficiency,
      correctness and completeness of the algorithm is ensured by several non-trivial
      properties that are proven in this paper. The algorithm has been applied in the
      important field of protein common 3D substructure searching. The methods
      implemented have been tested on several examples of protein families such as
      serine proteases, globins and cytochromes P450 additionally. The detected motifs
      have been compared to those found by multiple structural alignments methods.

PMID- 20047490
TI  - The accurate prediction of protein family from amino acid sequence by measuring
      features of sequence fragments.
AB  - The rapid advances in proteomic analyses coupled with the completion of multiple
      genomes have led to an increased demand for determining protein functions. The
      first step is classification or prediction into families. A method was developed
      for the prediction of protein family based only on protein sequence using support
      vector machine (SVM) models. In these models, the amino acids were classified
      into three categories (apolar, polar, and charged). Consecutive fragments ranging
      from one to five were annotated by amino acid type to define the protein features
      of each protein. SVM models were constructed based on the protein features of a
      training set of proteins and then examined with an independent set of proteins.
      The approach was tested for 20 protein families from the iProClass database of
      Protein Information Resources (PIR). For two-class SVM models, an average
      prediction accuracy of 0.9985 was achieved, while for multi-class SVM models an
      accuracy of 0.9941 was achieved. This study demonstrates that SVM based methods
      can accurately recognize and predict the protein family to which a sequence
      belongs based solely on its primary amino acid sequence.

PMID- 20047491
TI  - Tabu search and binary particle swarm optimization for feature selection using
      microarray data.
AB  - Gene expression profiles have great potential as a medical diagnosis tool because
      they represent the state of a cell at the molecular level. In the classification
      of cancer type research, available training datasets generally have a fairly
      small sample size compared to the number of genes involved. This fact poses an
      unprecedented challenge to some classification methodologies due to training data
      limitations. Therefore, a good selection method for genes relevant for sample
      classification is needed to improve the predictive accuracy, and to avoid
      incomprehensibility due to the large number of genes investigated. In this
      article, we propose to combine tabu search (TS) and binary particle swarm
      optimization (BPSO) for feature selection. BPSO acts as a local optimizer each
      time the TS has been run for a single generation. The K-nearest neighbor method
      with leave-one-out cross-validation and support vector machine with one-versus
      rest serve as evaluators of the TS and BPSO. The proposed method is applied and
      compared to the 11 classification problems taken from the literature.
      Experimental results show that our method simplifies features effectively and
      either obtains higher classification accuracy or uses fewer features compared to
      other feature selection methods.

PMID- 20047492
TI  - Use of wrapper algorithms coupled with a random forests classifier for variable
      selection in large-scale genomic association studies.
AB  - Modern large-scale genetic association studies generate increasingly high
      dimensional datasets. Therefore, some variable selection procedure should be
      performed before the application of traditional data analysis methods, for
      reasons of both computational efficiency and problems related to overfitting. We
      describe here a "wrapper" strategy (SIZEFIT) for variable selection that uses a
      Random Forests classifier, coupled with various local search/optimization
      algorithms. We apply it to a large dataset consisting of 2,425 African-American
      and non-Hispanic white individuals genotyped for 4,869 single-nucleotide
      polymorphisms (SNPs) in a coronary heart disease (CHD) case-cohort association
      study (Atherosclerosis Risk in Communities), using incident CHD and plasma low
      density lipoprotein (LDL) cholesterol levels as the dependent variables. We show
      that most SNPs can be safely removed from the dataset without compromising the
      predictive (classification) accuracy, with only a small number of SNPs (sometimes
      less than 100) containing any predictive signal. A statistical (SUMSTAT) approach
      is also applied to the dataset for comparison purposes. We describe a novel
      method for refining the subset of signal-containing SNPs (FIXFIT), based on an
      Extremal Optimization algorithm. Finally, we compare the top SNP rankings
      obtained by different methods and devise practical guidelines for researchers
      trying to generate a compact subset of predictive SNPs from genome-wide
      association datasets. Interestingly, there is a significant amount of overlap
      between seemingly very heterogeneous rankings. We conclude by constructing
      compact optimal predictive SNP subsets for CHD (less than 150 SNPs) and LDL (less
      than 300 SNPs) phenotypes, and by comparing various rankings for two well-known
      positive control SNPs for LDL in the apolipoprotein E gene.

PMID- 20047493
TI  - United-residue (UNRES) Langevin dynamics simulations of trpzip2 folding.
AB  - The folding mechanism of beta-hairpins might provide fundamental knowledge that
      helps us to understand how large proteins fold. However, all-atom molecular
      dynamics is difficult to do large-scale and long-time simulations, even for small
      peptides. In this article, we report a large-scale simulation of the beta-hairpin
      trpzip2 by Langevin dynamics with united-residue (UNRES) force field. We obtained
      374 successfully folding trajectories of trpzip2. The results show that trpzip2
      can fold into the native structure by adopting two different mechanisms: (1)
      zipper, and (2) simultaneous zipper and collapse. The former occurs with a larger
      probability. Furthermore, the folding of trpzip2 is heterogeneous. Our results
      clarify the inconsistencies in the current picture of the folding mechanisms of
      trpzip2 and other similar beta-hairpins.

PMID- 20047494
TI  - A computation to integrate the analysis of genetic variations occurring within
      regulatory elements and their possible effects.
AB  - Single nucleotide polymorphisms (SNPs) and short tandem repeats (STRs) are the
      most common genetic variations, are widespread within genomes, and form the
      diversity within species. These genetic variations affect many regulatory
      elements such as transcription factor binding sites (TFBSs), DNA methylation
      sites on CpG islands, and microRNA target sites; these elements have been found
      to play major as well as indirect roles in regulating gene expression. Currently,
      systems are available to display such genetic variation occurring within
      regulatory elements. To understand and display all the potential variation
      described above, we have developed a web-based system tool, the Regulatory
      Element and Genetic Variation Viewer (REGV Viewer [REGV]), which provides a
      friendly web interface for users and shows genetic variation information within
      regulatory elements by either inputting a gene list or selecting a chromosome by
      name. Moreover, our tool not only supports logic operation queries, but after a
      query is submitted, it also shows a high-throughput simulation, including
      combined data, statistical graphs, and graphical views of the genetic variants
      and regulatory elements. Additionally, when the SNP variation occurs within TFBSs
      and if the SNP allele frequency and TFBS position weight matrices (PWMs) are
      available, our system will show the new putative TFBSs resulting from the SNP
      variation.

PMID- 20047495
TI  - The molecular diagnosis of parechovirus infection: has the time come?

PMID- 20047496
TI  - Infant deaths associated with human parechovirus infection in Wisconsin.
AB  - BACKGROUND: From December 1987 through August 2004, lung tissue, nasopharyngeal
      swabs, and colon swab specimens obtained during 1263 autopsies of infants and
      young children were examined to assess the role of viruses in deaths of children
      aged <2 years. METHODS: Multiple cell cultures were used to isolate viruses. With
      4 exceptions, virus isolates were identified by neutralization,
      immunofluorescence assay, or enzyme immunoassay. RNA extracted from these 4
      isolates and associated autopsy specimens was tested using parechovirus-specific
      real-time polymerase chain reaction (RT-PCR) and sequencing assays. RESULTS:
      Specimens from 426 (34%) autopsies were positive for at least 1 virus;
      enteroviruses and adenoviruses were the most commonly identified. Human
      parechoviruses (HPeVs) were identified antigenically in isolates from 18
      decedents (all HPeV type 1) and by RT-PCR in isolates and multiple autopsy
      specimens from 4 decedents with untypeable virus isolates. Sequencing of the VP1
      region identified these 4 HPeVs as HPeV type 3 (n = 3) and HPeV type 6 (n = 1).
      Despite the detection of HPeV, the deaths of decedents 3 and 4 were determined to
      have been from noninfectious causes. CONCLUSIONS: These are the first confirmed
      HPeV type 3 and HPeV type 6 detections in the United States. This is also the
      initial report of fatal cases with associated HPeV type 3 infection. These
      results support prior findings associating HPeVs with serious disease in young
      children. Clinical testing for HPeVs and routine HPeV surveillance by public
      health laboratories will help determine the burden of disease caused by HPeVs.

PMID- 20047497
TI  - Gastroenteritis and food-borne disease in elderly people living in long-term
      care.
AB  - Elderly people in long-term care facilities (LTCFs) may be more vulnerable to
      infectious gastroenteritis and food-borne disease and more likely to experience
      serious outcomes. We review the epidemiology of gastroenteritis and food-borne
      diseases in elderly residents of LTCFs to inform measures aimed at preventing
      sporadic disease and outbreaks. Gastroenteritis in elderly people is primarily
      acquired from other infected persons and contaminated foods, although infections
      may also be acquired when residents have poor personal hygiene, have contaminated
      living environments or water, or have contact with infected pets. Early
      recognition of outbreaks and implementation of control measures is critical to
      reduce the effects on LTCF residents and staff members. Although outbreaks among
      LTCF residents are common, they are challenging to investigate, and there are
      still major gaps in our knowledge, particularly in regards to controlling
      noroviruses, the incidence and causes of specific infections, and sources of food
      borne disease.

PMID- 20047498
TI  - Developing a coordinated response to drug abuse in Pakistan.
AB  - This paper describes moves towards the coordination of efforts to respond to the
      worsening drug abuse situation in Pakistan which affects all segments of society.
      The efforts reported seek to rectify inconsistencies in treatment policy
      resulting in unsatisfactory outcomes. Examples of collaborative strategies with
      encouraging results need further underpinning and expansion. There is, however, a
      lack of realization at the policy level of the need to effect changes in
      treatment formulated on a consistent and evidence-based approach. Policy has
      therefore been reviewed and proposals made for a comprehensive treatment strategy
      in line with international best practices to deal with this problem effectively
      and efficiently. Establishment of an addiction study centre at university level
      to continue professional and academic development is suggested.

PMID- 20047499
TI  - Evidence for an effect of fetal growth on the risk of tuberculosis.
AB  - We examined the risk of tuberculosis in relation to birth weight and ponderal
      index among 21,596 Swedish twins born from 1926 through 1958. Using a cohort
      design, tuberculosis risk was 11% lower for every 500 g of birth weight (P = .05)
      and 8% lower for every 0.2 of ponderal index, calculated as birth weight in grams
      multiplied by 100 and divided by the cube of birth length in centimeters (P =
      .08). The association between birth weight and tuberculosis was stronger in male
      individuals than in female individuals. In co-twin control analyses among disease
      discordant monozygotic twins, tuberculosis risk was 46% lower for every 500 g of
      birth weight (P = .05). The association was stronger in male individuals (87%
      risk reduction; P = .02) than it was in female individuals (16% reduction; P =
      .62). A similarly stronger relation with male sex, compared with female sex, was
      found for ponderal index. Because associations among monozygotic twins are
      largely independent of shared genetic or environmental factors, we postulate that
      fetal growth may play a causal role in susceptibility to tuberculosis, possibly
      through early programming of immunity.

PMID- 20047500
TI  - How to shorten patient follow-up after treatment for Trypanosoma brucei gambiense
      sleeping sickness.
AB  - BACKGROUND. Clinical management of human African trypanosomiasis requires patient
      follow-up of 2 years' duration. At each follow-up visit, cerebrospinal fluid
      (CSF) is examined for trypanosomes and white blood cells (WBCs). Shortening
      follow-up would improve patient comfort and facilitate control of human African
      trypanosomiasis. METHODS. A prospective study of 360 patients was performed in
      the Democratic Republic of the Congo. The primary outcomes of the study were
      cure, relapse, and death. The WBC count, immunoglobulin M level, and specific
      antibody levels in CSF samples were evaluated to detect treatment failure. The
      sensitivity and specificity of shortened follow-up algorithms were calculated.
      RESULTS. The treatment failure rate was 37%. Trypanosomes, a WBC count of > or =
      100 cells/microL, and a LATEX/immunoglobulin M titer of 1:16 in CSF before
      treatment were risk factors for treatment failure, whereas human immunodeficiency
      virus infection status was not a risk factor. The following algorithm, which had
      97.8% specificity and 94.4% sensitivity, is proposed for shortening the duration
      of follow-up: at 6 months, patients with trypanosomes or a WBC count of > or = 50
      cells/microL in CSF are considered to have treatment failure, whereas patients
      with a CSF WBC count of > or = 5 cells/microL are considered to be cured and can
      discontinue follow-up. At 12 months, the remaining patients (those with a WBC
      count of > or = 6-49 cells/microL) need a test of cure, based on trypanosome
      presence and WBC count, applying a cutoff value of > or = 20 cells/microL.
      CONCLUSION. Combining criteria for failure and cure allows follow-up of patients
      with second-stage human African trypanosomiasis to be shortened to a maximum
      duration of 12 months.

PMID- 20047501
TI  - Effectiveness of monovalent rotavirus vaccine (Rotarix) against severe diarrhea
      caused by serotypically unrelated G2P[4] strains in Brazil.
AB  - BACKGROUND. In a Latin American trial, a monovalent G1P[8] rotavirus vaccine
      showed high efficacy against severe rotavirus diarrhea. Protection was lower
      against serotypically unrelated G2P[4] strains, which circulated infrequently.
      This case-control study was undertaken to assess the effectiveness of this
      monovalent G1P[8] rotavirus vaccine against G2P[4] strains in Brazil. METHODS.
      Case patients were children with severe G2P[4] rotavirus diarrhea who presented
      at a hospital in Recife, Brazil, from March 2006 through September 2008.
      Vaccination rates among case patients were compared with rates among 2 groups of
      control participants-children with rotavirus-negative diarrhea and children
      admitted for acute respiratory tract infection (ARI)-to calculate vaccine
      effectiveness, after controlling for the birth month and year. RESULTS. We
      enrolled 70 G2P[4] rotavirus-positive case patients with severe diarrhea, 484
      rotavirus-negative control participants with diarrhea, and 416 control
      participants with ARI, aged 6 months. Among children aged 6-11 months, the
      effectiveness of the vaccine against G2P[4] diarrhea was 77% (95% confidence
      interval [CI], 42%-91%) and 77% (95% CI, 43%-90%) among the rotavirus-negative
      control participants with diarrhea and control participants with ARI,
      respectively. Vaccine effectiveness in children aged 12 months decreased to -24%
      (95% CI, -190% to 47%) and 15% (95% CI, -101 to 64) among the rotavirus-negative
      control groups with diarrhea and ARI, respectively. CONCLUSIONS. This monovalent
      G1P[8] rotavirus vaccine was effective against severe G2P[4] rotavirus diarrhea
      among children aged 6-11 months. Effectiveness declined among children aged 12
      months, which suggests waning immunity.

PMID- 20047502
TI  - Quantifying the evolution and impact of antimalarial drug resistance: drug use,
      spread of resistance, and drug failure over a 12-year period in Papua New Guinea.
AB  - BACKGROUND. Antimalarial use is a key factor driving drug resistance and reduced
      treatment effectiveness in Plasmodium falciparum malaria, but there are few
      formal, quantitative analyses of this process. METHODS. We analyzed drug usage,
      drug failure rates, and the frequencies of mutations and haplotypes known to be
      associated with drug resistance over a 12-year period (1991-2002) in a site in
      Papua New Guinea. This period included 2 successive treatment policies:
      amodiaquine (AQ) or chloroquine (CQ) from 1991 through 2000 and their subsequent
      replacement by sulfadoxine-pyrimethamine (SP) plus AQ or SP plus CQ. RESULTS.
      Drug use approximated 1 treatment per person-year and was associated with
      increasing frequencies of pfcrt and pfmdr1 mutations and of treatment failure.
      The frequency of pfdhfr mutations also increased, especially after the change in
      treatment policy. Treatment failure rates multiplied by 3.5 between 1996 and 2000
      but then decreased dramatically after treatment policy change. CONCLUSIONS. With
      high levels of resistance to CQ, AQ, and SP, the deployment of the combination of
      both drugs appears to increase clinical effectiveness but does not decelerate
      growth of resistance. Our estimates of mutation and haplotype frequencies provide
      estimates of selection coefficients acting in this environment, which are key
      parameters for understanding the dynamics of resistance.

PMID- 20047503
TI  - HIV infection and aging independently affect brain function as measured by
      functional magnetic resonance imaging.
AB  - We investigated the interactions between human immunodeficiency virus (HIV)
      infection and aging and their effects on brain function demands by means of
      functional magnetic resonance imaging (fMRI). A multiple-regression model was
      used to study the association and interaction between fMRI measures, HIV
      serostatus, and age for 26 HIV-infected subjects and 25 seronegative subjects.
      Although HIV serostatus and age independently affected fMRI measures, no
      interaction occurred. Functional brain demands in HIV-positive subjects were
      equivalent to those of HIV-negative subjects who were 15-20 years older. Frailty
      parallels between HIV infection and aging could result from continued
      immunological challenges depleting resources and triggering increased metabolic
      demands. In the future, fMRI could be a noninvasive biomarker to assess HIV
      infection in the brain.

PMID- 20047504
TI  - Combining low-dose cyclophosphamide with GM-CSF-secreting prostate cancer
      immunotherapy enhances antitumor immune effects.
AB  - Prostate GVAX((R)) is an allogeneic cell-based prostate cancer vaccine engineered
      to secrete GM-CSF. The release of GM-CSF by this immunotherapy serves to recruit
      dendritic cells, which then present tumor antigens to T cells, thus initiating
      antitumor immune responses. However, preclinical data show that, when used alone,
      cell-based immunotherapy is generally unable to break specific T-cell tolerance
      in tumor-bearing hosts. The study by Wada and colleagues employed an
      autochthonous prostate cancer mouse model to demonstrate that low-dose
      cyclophosphamide given prior to a cell-based GM-CSF-secreting vaccine (T-GVAX)
      abrogated immune tolerance, augmented prostatic CD8(+) T-cell infiltration,
      mediated depletion of regulatory T cells (Tregs), and increased expression of
      dendritic cell maturation markers. In addition, this combination decreased the
      wet weight of mouse prostate glands, lowered histological tumor scores, and
      increased the density of apoptotic bodies. These findings add to existing data
      from other preclinical models showing enhancement of antitumor immunity when
      cyclophosphamide is administered in sequence with GM-CSF-secreting immunotherapy
      for the treatment of breast and pancreatic cancers. These studies provide a
      rationale for designing clinical trials that combine low-dose cyclophosphamide
      with GM-CSF-secreting cell-based immunotherapy in patients with prostate and
      other cancers.

PMID- 20047505
TI  - Potential for long-acting muscarinic antagonists in chronic obstructive pulmonary
      disease.
AB  - IMPORTANCE OF THE FIELD: The prevention and relief of symptoms by regular use of
      bronchodilators is central to the pharmacological management of chronic
      obstructive pulmonary disease (COPD). AREAS COVERED IN THIS REVIEW: The aim of
      this article is to review the effects of inhaled muscarinic antagonists in the
      treatment of stable COPD. WHAT THE READER WILL GAIN: An update of the clinical
      studies performed with the long-acting inhaled muscarinic antagonist (LAMA)
      tiotropium bromide in patients with COPD is given. In recent years, combinations
      of a LAMA and a long-acting inhaled beta2-agonist (LABA), and 'triple therapy'
      consisting of a LAMA, a LABA, and an inhaled steroid are being developed. Issues
      of safety of inhaled anticholinergics in COPD are discussed and a short overview
      of new LAMAs being developed for COPD is given. TAKE HOME MESSAGES: The
      importance of anticholinergic drug treatment in COPD was largely advanced by the
      development of the first LAMA, tiotropium bromide. The vast experience obtained
      with tiotropium bromide has paved the way for new LAMAs such as aclidinium
      bromide and glycopyrrolate (NVA-237).

PMID- 20047506
TI  - Ketoconazole enantiomer for the treatment of diabetes mellitus.
AB  - The impact of hypercortisolism on multiple metabolic conditions is well
      recognized; the metabolic manifestations of Cushing's syndrome overlap with those
      seen in type 2 diabetes and the metabolic syndrome. Ketoconazole (KTZ), a widely
      used antifungal agent that inhibits various enzymes in adrenal cortisol
      synthesis, is effective in treating hypercortisolemia, but its use is limited by
      toxicities. KTZ is a racemic compound of two cis-enantiomers: (2R,4S)-(+)-KTZ and
      (2S,4R)-(-)-KTZ. The consideration of an enantiomer with selective effect but
      minimal metabolic toxicity has driven the development of DIO-902 ([2S,4R]-[-]
      KTZ) for the treatment of patients with type 2 diabetes and the metabolic
      syndrome. To evaluate the safety profile and effect of KTZ enantiomer, (2S,4R)-(
      )-KTZ, on cortisol production, glycemia, and lipid profiles in patients with type
      2 diabetes. Review of multiple published studies and examination of preliminary
      results from a Phase IIb clinical trial. Twelve weeks of treatment with DIO-902
      resulted in reduced levels of HbA1c, FPG, total and LDL cholesterol as well as
      weight loss and decreased BP. In a previously conducted Phase IIa study, C
      reactive protein levels decreased with DIO-902 treatment. Unfortunately, the
      development of this agent has been terminated due to unacceptable safety
      profiles.

PMID- 20047507
TI  - Targeting silibinin in the antiproliferative pathway.
AB  - IMPORTANCE OF THE FIELD: Due to the failure and severe toxicity of cancer
      chemotherapy, silibinin, a natural flavonoid from the seeds of milk thistle, has
      recently received more attention for its potential anticancer and nontoxic roles
      in animals and humans. Silibinin has clearly demonstrated inhibition of multiple
      cancer cell signaling pathways, including growth inhibition, inhibition of
      angiogenesis, chemosensitization, and inhibition of invasion and metastasis.
      Cumulative evidence implicates that silibinin is a potential agent for cancer
      chemoprevention and chemotherapy. AREAS COVERED IN THIS REVIEW: Our aim is to
      discuss the recent progress of silibinin in regulating multiple anticancer
      proliferative signaling pathways; the review covers literature mainly from the
      past 3 - 5 years. WHAT THE READER WILL GAIN: One of the strategies for tumor
      therapy is eradication of cancer cells through targeting specific cell
      proliferative pathways. This review highlights the current knowledge of silibinin
      in regulating multiple cellular proliferative pathways in cancer cells, including
      receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle
      regulatory and apoptotic signaling pathways. TAKE HOME MESSAGE: The molecular
      mechanisms of silibinin-mediated antiproliferative effects are mainly via
      receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle
      regulatory and apoptotic signaling pathways in various cancer cells. Targeting
      inhibition of proliferative pathways through silibinin treatment may provide a
      new approach for improving chemopreventive and chemotherapeutic effects.

PMID- 20047508
TI  - Topically applied capsaicin inhibits sensitivity to touch but not to warmth or
      heat-pain in the region of secondary mechanical hyperalgesia.
AB  - The aim of this study was to investigate tactile sensitivity near the site of
      primary hyperalgesia evoked by capsaicin applied topically to the dorsolateral
      aspect of the hand. In the first experiment (N = 15), touch thresholds increased
      in the fifth finger ipsilateral to the topically applied capsaicin, but remained
      unchanged at greater distances from the site of capsaicin treatment. In a second
      experiment (N = 12), the effect of the capsaicin treatment on sensations evoked
      not only by light touch but also by warmth, heat-pain, and pressure-pain to a 2
      mm diameter steel probe was investigated in the fifth finger. Again, tactile
      sensitivity was inhibited at the fifth finger, even though stimulation with a
      cotton bud evoked no discomfort; moreover, sensitivity to warmth and heat-pain
      were unimpaired. However, sensitivity to pressure-pain increased in the fifth
      finger after the capsaicin treatment, possibly due to activation of nociceptors
      sandwiched between the probe tip and bone that normally responded to sharp
      stimuli. These findings suggest that the central mechanisms that mediate
      secondary mechanical hyperalgesia suppress sensitivity to innocuous tactile
      sensations. This effect may contribute to tactile hypoesthesia in chronic pain
      conditions.

PMID- 20047509
TI  - Cortical control of appropriate tongue protrusion during licking in cats-
      increase in regional cerebral blood flow (rCBF) of the contralateral area P and
      in tongue protrusion after the unilateral area P lesion.
AB  - Adequate tongue protrusion may be regulated by cat bilateral area P (the motor
      cortex for jaw and tongue movements) (Hiraba and Sato, Somatosens Mot Res
      2005b;22:183-192). The ICMS (intracortical microstimulation) in the unilateral
      area P evoked motor effects of tongue protrusion without deviation (Hiraba and
      Sato, Somatosens Mot Res 2004;23:1-12), and cats with the unilateral lesion of
      area P showed abnormal tongue protrusion without deviation during licking (Hiraba
      and Sato, Somatosens Mot Res 2005b;22:183-192). Further, the measurements of the
      regional cerebral blood flow (rCBF) in the bilateral jaw and tongue motor
      cortical areas were shown to have the same activity rate during the lateral
      licking (Hiraba and Sato, Somatosens Mot Res 2005c;22:307-317). We assumed from
      these results that cortical control for tongue protrusion was executed by
      networks between the bilateral area P including inhibitory interneurons. We
      prepared the measurable cats of the rCBF in the contralateral side after the
      unilateral area P lesion. Changes in the rates of rCBF and tongue protrusion
      during licking were examined over a long time course of about 1-2 months after
      the unilateral area P lesion. All cats after the unilateral area P lesion showed
      increased rate (double or triple in comparison with the normal ones) of rCBF of
      the contralateral area P in the early (0-20 days) phase. On the other hand,
      increased rates of tongue protrusion were about 120% in the early phase, and
      about 180% in the middle (21-35 days) and late (36-last days) phases. The results
      support the organization of networks between bilateral area P including the
      inhibitory interneurons.

PMID- 20047511
TI  - Influence of vision and motor imagery styles on equilibrium control during whole
      body rotations.
AB  - To investigate the influence of vision and motor imagery styles on equilibrium
      control, displacements of the supporting foot during spontaneous whole-body
      rotations ("pirouette") by expert female ballet dancers were analyzed using three
      dimensional kinematics. Four turn types were defined according to direction
      (clockwise, CW vs. counterclockwise, CCW) and supporting foot (SF, left vs.
      right). Visual influences were examined by including two visual conditions
      (blindfolded vs. full-vision). Motor imagery styles were determined using the
      Vividness of Movement Imagery Questionnaire (VMIQ) (Kinesthetic, n = 4 vs.
      Visual/Kinesthetic, n = 6). Turning direction preference was assessed by a closed
      response questionnaire in which all dancers indicated that they preferred CW turn
      direction. Kinesthetic dancers showed more SF displacement during CCW (non
      preferred direction) than CW (preferred direction) pirouettes. However,
      Visual/Kinesthetic dancers showed no significant effect of turn direction.
      Furthermore, Kinesthetic dancers showed no significant effect of vision on SF
      displacement whereas Visual/Kinesthetic dancers showed significantly higher SF
      displacement when vision was occluded. Thus there appears to be a selective
      effect of vision on Visual/Kinesthetic dancers, and a selective effect of turn
      direction on Kinesthetic dancers. These results suggest that perceptual styles
      should be taken into consideration when training tasks that require fine
      equilibrium control because the factors that perturb balance differ depending on
      perceptual style.

PMID- 20047510
TI  - Functional connectivity for somatosensory and motor cortex in spastic diplegia.
AB  - Functional connectivity (fcMRI) was analyzed in individuals with spastic diplegia
      and age-matched controls. Pearson correlations (r-values) were computed between
      resting state spontaneous activity in selected seed regions (sROI) and each voxel
      throughout the brain. Seed ROI were centered on foci activated by tactile
      stimulation of the second fingertip in somatosensory and parietal dorsal
      attention regions. The group with diplegia showed significantly expanded networks
      for the somatomotor but not dorsal attention areas. These expanded networks
      overran nearly all topological representations in somatosensory and motor areas
      despite a sROI in a fingertip focus. A possible underlying cause for altered
      fcMRI in the group with dipegia, and generally sensorimotor deficits in spastic
      diplegia, is that prenatal third trimester white-matter injury leads to localized
      damage to subplate neurons. We hypothesize that intracortical connections become
      dominant in spastic diplegia through successful competition with diminished or
      absent thalamocortical inputs. Similar to the effects of subplate ablations on
      ocular dominance columns (Kanold and Shatz, Neuron 2006;51:627-638), a spike
      timing-dependent plasticity model is proposed to explain a shift towards
      intracortical inputs.

PMID- 20047512
TI  - Quantitative determination of 3,4-methylenedioxymethamphetamine by thin-layer
      chromatography in ecstasy illicit pills in Tehran.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is the major ingredient of ecstasy
      illicit pills. It is a hallucinogen, central nervous system stimulant, and
      serotonergic neurotoxin that strongly releases serotonin from serotonergic nerves
      terminals. Moreover, it releases norepinephrine and dopamine from nerves
      terminal, but to a lesser extent than serotonin. Poisoning and even death from
      abusing MDMA-containing ecstasy illicit pills among abusers is usual. Thus,
      quantitative determination of MDMA content of ecstasy illicit pills in illicit
      drug bazaar must be done regularly to find the most high dose ecstasy illicit
      pills and removing them from illicit drug bazaar. In the present study, MDMA
      contents of 13 most abundant ecstasy illicit pills were determined by
      quantitative thin-layer chromatography (TLC). Two procedures for quantitative
      determination of MDMA contents of ecstasy illicit pills by TLC were used:
      densitometric and so-called 'scraping off' methods. The former was done in a
      reflection mode at 285 nm and the latter was done by absorbance measurement of
      eluted scraped off spots. Limit of detection (LOD), considering signal-to-noise
      ratio (S/N) of 2, and limit of quantification (LOQ), regarding S/N of 10, of
      densitometric and scraping off methods were 0.40 microg, 1.20 microg, and 6.87
      mug, 20.63 microg, respectively. Repeatabilities (within-laboratory error) of
      densitometric and scraping off methods were 0.5% and 3.6%, respectively. The
      results showed that the ecstasy illicit pills contained 24-124.5 mg and 23.9
      122.2 mg MDMA by densitometric and scraping off methods, respectively.

PMID- 20047514
TI  - Salmonella brain abscess in a patient on chronic azathioprine therapy for
      myasthenia gravis: report of an unusual case and review of literature in the
      postantibiotic era.
AB  - Focal intracranial infections caused by Salmonella species in adults are
      exceedingly uncommon. Structural brain injury with coexisting immunocompromised
      status appears to predispose adults to this rare manifestation of Salmonella
      infection. We report a case of Salmonella brain abscess in a patient with
      myasthenia gravis on chronic azathioprine therapy without any prior structural
      brain lesion. We reviewed world literature and discuss their analysis of
      Salmonella brain abscess in adult population in the postantibiotic era.

PMID- 20047515
TI  - Relative roles of heme-irons and globin-thiols in the genesis of acellular
      hemoglobin mediated vasoconstriction.
AB  - In addition to heme-irons, reactive (beta-globin thiols (betaCys93s) of
      hemoglobin (Hb) also have been shown to interact with endogenous nitric oxide
      (NO) thereby contributing to vascular tone regulation. What relative roles do
      these NO binding sites contribute to the overall Hb-mediated vasoactivity?
      Several test Hbs with either or both the NO binding sites preliganded or blocked
      were prepared and tested in a rat thoracic aortic ring model. Hbs tested were:
      NEM-Hb (ferrous Hb with masked thiols), HbNO (ferrous Hb preliganded with NO),
      Hb(+)CN (ferric Hb liganded with CN(-)), NEM-HbNO and NEM-Hb(+)CN (Hbs with both
      heme-iron and cysteine sites preliganded or blocked). Typically, >0.2 microM
      control Hb significantly increased isometric tension in agonist stimulated vessel
      rings (58.1 +/-7.0% over baseline). At comparable concentrations, NEM-Hb also
      caused a significant contraction (50.7+/-9.5%) while HbNO and Hb(+)CN did not (
      5.5+/-6.0% and -3.7+/-4.6%, respectively). For these Hbs, masking thiols as well
      did not significantly alter respective vascular effects. Ferrous sperm whale
      myoglobin (Mb), which has no reactive thiol, elicited a significant contraction
      (55.1+/-13.2%) while metMb did not (-0.8+/-3.2%), suggesting the relative
      importance of heme-iron ligand and oxidation state in Hb vasoactivity.
      Additionally, ferrous or ferric equine heart cytochrome-C, a heme protein with no
      readily available heme-iron and cysteine binding sites, did not elicit notable
      contraction. Human Hb variants in which (betaCys93s are deleted or substituted
      with non-cysteine residues did not reveal any documented significant hemodynamic
      abnormalities. These results indicate that reactive globin-thiols do not appear
      to play a prominent role relative to heme-irons in Hb-mediated vasoconstriction.

PMID- 20047516
TI  - Evaluation of various ions and compounds on nitrilase produced from Streptomyces
      sp.
AB  - The nitrilase produced from a new isolate is evaluated for its activity in
      presence of a number of different ions and compounds at optimal conditions. It
      was found that the activity of nitrilase increased up to 10-20% in presence of
      most of the divalent ions at a concentration of 5 mM relative to the control.
      Silver, mercury, tin, DTT, ascorbic acid and thiourea, respectively, were
      observed as potential inhibitors of the enzyme catalysis. The investigation on
      storage stability of whole cells in presence of a number of stabilizers showed
      that the enzyme is stable (relative activity 50%) for more than 120 days at
      various temperatures.

PMID- 20047517
TI  - Relationship between CX3CR1 genetic polymorphism and carotid atherosclerosis.
AB  - To investigate the possible association between V249I and T280M polymorphisms and
      carotid atherosclerosis (CAS) in a Han population in northern China we studied
      328 patients with increased carotid artery intima-media thickness (C-IMT) and 292
      healthy controls with normal C-IMT. T280M and V249I polymorphic genotypes of
      CX3CR1 were determined by polymerase chain reaction restriction fragment length
      polymorphism. Results showed that the M280 allele frequency in CAS group was
      significantly lower than that in the controls. Logistic regression analysis
      revealed that the decreased frequency of the M280 allele was an independent risk
      factor for CAS.

PMID- 20047518
TI  - The observation of phenotypic changes of Schwann cells after rat sciatic nerve
      injury.
AB  - To describe the phenotypic changes of Schwann cells during nerve regeneration, we
      made two different neurorrhaphy models after rat sciatic nerves injury, the
      epineurium neurorrhaphy and small gap bridging suture. Then, at selected time
      points after surgery (1d, 3d, 5d, 7d, 2 weeks, 3 weeks), the materials were drawn
      for detecting the expression of GFAP, Sox2, Krox20 by immunofluorescence. GFAP is
      expressed in non-myelin-forming Schwann cells and Krox20 is a marker for myelin
      forming cells in the adult nerve. Sox2 is a marker for neural stem and progenitor
      cells. Our findings showed the rule of phenotypic changes of Schwann cells during
      nerve regeneration. Furthermore, the difference in the phenotypic changes of
      Schwann cells between two operation methods indicated that the small gap changes
      the regenerated microenvironment and may be one of the reasons that small gap
      bridging suture is superior to the epineurium suture.

PMID- 20047519
TI  - The delayed repair of sciatic nerve defects with tissue-engineered nerve grafts
      in rats.
AB  - The purpose of this study was to evaluate the feasibility of using tissue
      engineered nerve grafts for delayed repair of peripheral nerve defects. A 1-month
      delayed, 10-mm long sciatic nerve defect was created for rats, which were divided
      into three grafted groups and a non-grafted group. For bridging the nerve
      defects, the rats in three grafted groups were subjected to surgical repair with
      tissue-engineered nerve grafts made of a chitosan/polyglycolic acid (PGA) conduit
      filled with neural stem cells (NSCs), chitosan/PGA conduits, and autologous nerve
      grafts, respectively. At 3 months after nerve grafting, the data from
      electrophysiology, retrograde tracing and histological investigation revealed
      that the better outcomes in sciatic nerve regeneration and target muscle re
      innervation were achieved in three grafted groups as compared to those in non
      grafted group without major differences between three grafted groups. Our results
      suggest that grafting of chitosan/PGA conduits might be a promising technique for
      repairing peripheral nerve injuries after a 1-month delay, while introduction of
      NSCs seem to show no significant additional benefits to regenerative outcomes.

PMID- 20047520
TI  - Programmed cell death 5 factor enhances triptolide-induced fibroblast-like
      synoviocyte apoptosis of rheumatoid arthritis.
AB  - OBJECTIVE: To study the effect of programmed cell death 5 (PDCD5) on apoptosis of
      rheumatoid arthritis fibroblast-like synoviocyte (RAFLS) induced by triptolide.
      METHOD: Cultured synovial cells in vitro from RA patients were transfected with
      Ad-PDCD5. In protein level, expression of PDCD5 protein in Ad-PDCD5 transfected
      RAFLS was detected by Western blot. RAFLS transfected with Ad-PDCD5 were cultured
      in presence or absence of triptolide and RAFLs apoptosis was determined by flow
      cytometry. RESULT: Transfection of RAFLS with increasing concentration of Ad
      PDCD5 (50-300 MOI) resulted in dose-dependent increase of PDCD5 production.
      Apoptotic cells percentage of no transfection group, Ad-null group and Ad-PDCD5
      group were, respectively, (22.41 +/- 3.87)%, (28.77 +/- 12.97)%, and (48.87 +/-
      12.69)%. Alternatively, transfection without triptolide stimuli had no effect.
      The data showed that gene transfection of PDCD5 alone without triptolide was not
      sufficient to activate RAFLS apoptosis; PDCD5 acted as an enhancer rather than
      inductor of apoptosis. CONCLUSION: Overexpression of PDCD5 could enhance
      apoptosis of RA FLS induced by triptolide; PDCD5 may be a potential therapeutic
      target to RA.

PMID- 20047521
TI  - LTB4 can stimulate human osteoclast differentiation dependent of RANKL.
AB  - Our previous study showed that Leukotriene B4 can directly stimulate osteoclast
      differentiation independent of RANKL. In order to determine whether Leukotriene
      B4 could indirectly stimulate human osteoclast differentiation through increasing
      RANKL expression of rheumatoid arthritis fibroblast-like synoviocytes, we utilize
      the coculture model of rheumatoid arthritis fibroblast-like synoviocytes and
      monocyte, which were stimulated in the presence of 2.5 ng/ml M-CSF in the control
      group, 2.5 ng/ml M-CSF+10(-8)M LTB4 in the experimental group a, and 2.5 ng/ml M
      CSF+10(-8)M LTB4+100 ng/ml OPG in the experimental group b. After culture for 3
      weeks, the number of multinucleated TRAP staining positive osteoclast-like cells
      stained with TRAP was counted to evaluate the differentiation effect in each
      group. There was almost no osteoclast-like cell in the control group and the
      experimental group b. There were many osteoclast-like cells in the experimental
      group a. These results indicated that Leukotriene B4 is capable of inducing
      osteoclast differentiation by a RANKL-dependent mechanism.

PMID- 20047522
TI  - The prediction and prevention of preterm birth and its consequences: an unmet
      challenge to perinatal medicine, science and society.

PMID- 20047523
TI  - Women's attitudes to and perceptions of oral health and dental care during
      pregnancy.
AB  - AIMS: To assess pregnant women's opinions on and perceptions of oral health and
      their relationship to oral hygiene and dental care practices. METHODS:
      Questionnaire survey on perceived oral health, oral hygiene and utilization of
      dental services among 649 nulliparae attending for antenatal care at all public
      antenatal clinics in Adelaide, South Australia. RESULTS: Women rated their
      general health significantly better than their oral health (P<0.001) and
      attributed more importance to healthy teeth for their baby than for themselves
      (P<0.001). Only 35% had dental care during pregnancy; 35% had no dental visit for
      at least two years and 27% reported cost as a major deterrent. Eighteen percent
      had experienced gingival bleeding before pregnancy and 41% during pregnancy.
      Gingival bleeding outside pregnancy was clearly related to perceived oral health
      (P<0.001), but this was less so for bleeding during pregnancy. The latter was not
      related to age, level of education, employment, marital status, or smoking
      habits. Only 38% of women with gingival bleeding in pregnancy had a dental care
      visit in pregnancy and 28% considered their oral health as very good.
      CONCLUSIONS: Many pregnant women do not perceive gingival bleeding as indicating
      inflammatory disease and seek no professional help for it. Maternity care
      providers need to devote more attention to oral health in antenatal clinics and
      antenatal education.

PMID- 20047524
TI  - Atosiban vs. ritodrine as a tocolytic in external cephalic version at term: a
      prospective cohort study.
AB  - OBJECTIVE: To compare the success rate of external cephalic version (ECV) at term
      using ritodrine or atosiban as a tocolytic agent. STUDY DESIGN: Prospective
      cohort study with a sample of 236 pregnant women with a breech presentation at
      term, from November 2006 to March 2008. Data have been analyzed from the moment
      the cephalic version is performed until the time of delivery. RESULTS: ECV
      success rate using ritodrine as a tocolytic agent was 56.8% compared to 31.4%
      with atosiban. Ritodrine increases the version success potential more
      significantly than atosiban (P<0.05). In both cases, the use of ECV reduced the
      rate of cesarean sections, although a higher number of versions are required with
      atosiban [numbers needed to treat (NNT)=9.08] to avoid a cesarean section
      compared to ritodrine (NNT=3.41). CONCLUSIONS: Ritodrine seems better than
      atosiban as tocolytic agent for ECVs.

PMID- 20047525
TI  - Role of parental folate pathway single nucleotide polymorphisms in altering the
      susceptibility to neural tube defects in South India.
AB  - AIM: To investigate the role of four parental folate pathway single nucleotide
      polymorphisms (SNPs) i.e., methylene tetrahydrofolate reductase (MTHFR) 677C>T,
      MTHFR 1298A>C, methionine synthase reductase (MTRR) 66A>G and glutamate
      carboxypeptidase (GCP) II 1561C>T on susceptibility to neural tube defects (NTDs)
      in 50 couples with NTD offspring and 80 couples with normal pregnancy outcome.
      RESULTS: Maternal MTHFR 677C-->T (odds ratio (OR): 2.69, 95% confidence interval
      (CI): 1.35-5.34) and parental GCP II 1561C-->T (maternal: OR: 1.89, 95% CI: 1.12
      3.21 and paternal: OR: 3.23, 95% CI: 1.76-5.93) were found to be risk factors for
      a NTD. Both paternal and maternal GCP II T-variant alleles were found to interact
      with MTHFR 677T- and MTRR G-variant alleles in increasing the risk for NTD.
      Segregation of data based on type of defect revealed an association between
      maternal 677T-allele and meningomyelocele (OR: 9.00, 95% CI: 3.77-21.55,
      P<0.0001) and an association between parental GCP II 1561T-allele and anencephaly
      (maternal: OR: 2.25, 95% CI: 1.12-4.50, P<0.05 and paternal: OR: 4.26, 95% CI:
      2.01-9.09, P<0.001). CONCLUSIONS: Maternal MTHFR C677T and parental GCP II C1561T
      polymorphisms are associated with increased risk for NTDs. Apart from individual
      genetic effects, epistatic interactions were also observed.

PMID- 20047526
TI  - The potential of 4D sonography in the assessment of fetal neurobehavior-
      multicentric study in high-risk pregnancies.
AB  - OBJECTIVE: An evolving challenge for obstetrician is to better define normal and
      abnormal fetal neurological function in utero in order to better predict
      antenatally which fetuses are at risk for adverse neurological outcome. PATIENTS
      AND METHODS: Prenatal neurological assessment in high-risk fetuses using four
      dimensional ultrasound applying the recently developed Kurjak antenatal
      neurodevelopmental test (KANET). Postnatal neurological assessment was performed
      using Amiel Tison's neurological assessment at term (ATNAT) for all live-borns
      and general movement (GM) assessment for those with borderline and abnormal
      ATNAT. RESULTS: Inclusion criteria were met by 288 pregnant women in four centers
      of whom 266 gave birth to a live-born baby. It was revealed that 234 fetuses were
      neurologically normal, 7 abnormal and 25 borderline. Out of 7 abnormal fetuses
      ATNAT was borderline in 5 and abnormal in 2, whereas GM assessment was abnormal
      in 5 and definitely abnormal in 2. Out of 25 KANET borderline fetuses, ATNAT was
      normal in 7, borderline in 17 and abnormal in 1, whereas the GM assessment was as
      follows: normal optimal in 4, normal suboptimal in 20, and abnormal in 1. In
      summary, out of 32 borderline and abnormal fetuses ATNAT was normal in 7,
      borderline in 22 and abnormal in 3; GM assessment was normal optimal in 4, normal
      suboptimal in 20, abnormal in 6 and definitely abnormal in 2. CONCLUSION: The
      sonographic test requires further studies before being recommended for wider
      clinical practice.

PMID- 20047527
TI  - Racial/ethnic disparities in infant mortality.
AB  - AIMS: This study examines predictors of neonatal and postneonatal mortality among
      infants born to black, white, and Hispanic women. METHODS: Linked birth/infant
      death records from North Carolina for the period 1999-2007 were the source of
      data. Logistic regression models were constructed to estimate the effect of
      maternal and infant characteristics on neonatal (<28 days) and postneonatal (28
      364 days) mortality. RESULTS: Analyses revealed no racial/ethnic differences in
      neonatal mortality, but increased risk among black infants for postneonatal
      death. Inadequate prenatal care was associated with an increased risk for
      neonatal mortality across all three racial/ethnic groups. Younger maternal age
      and lower educational levels were associated with postneonatal deaths for black
      and white women, but not Hispanic. A previous child loss, being unmarried and
      labor/delivery complications increased the risk for postneonatal mortality only
      among white women. Black infants had higher rates of death attributed to sudden
      infant death syndrome (SIDS), infections, low birth weight (LBW)/prematurity,
      respiratory conditions, and injuries. CONCLUSIONS: Early initiation of prenatal
      care, access to risk-appropriate obstetric and neonatal services, and
      participation in intervention programs that support parenting of LBW/preterm
      infants throughout the first year of life are likely to yield the greatest impact
      in reducing infant mortality.

PMID- 20047530
TI  - Evaluation of errors in a clinical laboratory: a one-year experience.
AB  - BACKGROUND: Efficient laboratory service is the cornerstone of modern health care
      systems. Scientific innovations have contributed to substantial improvements in
      the field of laboratory science, but errors still prevail. These errors are
      classified as preanalytical, analytical and postanalytical, depending upon the
      time of presentation. METHODS: The data for 67,438 routine venous blood specimens
      were scrutinized, and errors were documented over the period of 1 year in the
      clinical biochemistry laboratory of Govind Ballabh Pant Hospital in Delhi, India.
      RESULTS: Preanalytical errors were most common, with a frequency of 77.1%
      followed by postanalytical 15% and analytical 7.9%, respectively. CONCLUSIONS:
      Our study illustrates the importance of proper venipuncture procedures,
      analytical expertise and correct transcription of numerical data for precise and
      accurate reporting of results to clinicians. There is an urgent need for close
      inter-departmental cooperation to meet the goal of ensuring patient well being.

PMID- 20047531
TI  - Plasma nitrite/nitrate concentrations in patients with schizophrenia.
AB  - BACKGROUND: Nitric oxide (NO) is known to be a signaling molecule with many
      physiogical functions including apoptotic process regulation. Since apoptosis may
      contribute to the pathophysiology of schizophrenia, this study was undertaken to
      determine the plasma concentrations of NO in schizophrenics. METHODS:
      Nitrite/nitrate (NO(2)(-)/NO(3)(-)) concentrations were measured in plasma from
      40 patients with schizophrenia, and 36 age- and gender-matched healthy persons
      using a colorimetric test. RESULTS: Plasma NO(2)(-)/NO(3)(-) concentrations were
      significantly higher in patients with schizophrenia (102.8+/-34.7 micromol/L,
      p<0.0001) than in controls (69.2+/-13.2 micromol/L). Also, mean NO(2)(-)/NO(3)(-)
      values in female patients and controls were significantly higher (118.2+/-44.7
      micromol/L, p<0.001; 74.8+/-16.1 micromol/L, p<0.05, respectively) compared to
      males (94.7+/-25.3 micromol/L, 67.6+/-10.8 micromol/L). Significant correlation
      was seen between plasma NO(2)(-)/NO(3)(-) concentrations and heredity, number of
      episodes and peripheral blood mononuclear cell (PBMC) caspase-3 activity, which
      was significantly higher in patients than in controls (p<0.05). There was no
      significant difference in NO(2)(-)/NO(3)(-) concentrations between patients with
      different Positive and Negative Syndrome Scale (PANSS) scores or between patients
      treated with haloperidol (97.2+/-31.2 micromol/L) and those treated with other
      atypical antipsychotic drugs (109.8+/-33.7 micromol/L). Both parameters showed no
      significant differences between smokers and non-smokers. CONCLUSIONS: This study
      showed that plasma NO(2)(-)/NO(3)(-) concentrations were significantly increased
      in patients with schizophrenia, being significantly higher in female than male
      patients, and showing a significant correlation with heredity, number of episodes
      and PBMC caspase-3 activity. These results suggest that NO could be considered an
      inducer or regulator of apoptosis in patients with schizophrenia.

PMID- 20047532
TI  - Improvement of the cardiac marker N-terminal-pro brain natriuretic peptide
      through adjustment for renal function: a stratified multicenter trial.
AB  - BACKGROUND: N-terminal-pro brain natriuretic peptide (NT-proBNP) is a useful
      cardiac marker that is also influenced by renal dysfunction. It was our objective
      to assess the relationship between NT-proBNP concentrations in plasma and
      worsening renal function, and to attempt adjustment of NT-proBNP for renal
      dysfunction in a prospective, stratified multi-center study. METHODS: We
      stratified 203 male patients according to their cardiac status and the estimated
      glomerular filtration rate (eGFR). Cardiac disease was assessed by medical
      history, physical examination and standardized echocardiography. Patients were
      stratified according to the following: absence of cardiac history and
      abnormalities (control, CTRL, n=66), cardiac history without left ventricular
      hypertrophy (LVH) or left ventricular systolic dysfunction (LVD) (history, n=30),
      LVH without systolic dysfunction (LVH, n=68), and LVD [ejection fraction (EF)
      <40%, LVD, n=39]. Renal disease was stratified according to the eGFR: 15-30
      mL/min (n=52), 31-75 mL/min (n=99), and >75 mL/min (n=52). RESULTS: NT-proBNP was
      correlated with eGFR in the entire study population and for all levels of cardiac
      disease (all p<0.01). Regression analysis allowed adjustment of NT-proBNP for
      eGFR in a continuous manner, and this adjustment significantly improved the
      predictive value (receiver operating characteristic curve for symptomatic LVD
      from 0.80 to 0.86, p<0.01; sensitivity from 74% to 83% and specificity from 68%
      to 79%). CONCLUSIONS: NT-proBNP correlates inversely and significantly with eGFR
      throughout all levels of cardiac strata. We propose for the first time a
      continuous adjustment algorithm which markedly improves the predictive values of
      NT-proBNP in male patients with impaired renal function.

PMID- 20047533
TI  - Serum total and free sialic acid in patients with chronic liver disease.

PMID- 20047534
TI  - Measurement of nitrotyrosine in plasma by immunoassays is fraught with danger:
      commercial availability is no guarantee of analytical reliability.

PMID- 20047537
TI  - Why we need tobacco sales data for good tobacco control.

PMID- 20047538
TI  - Heart failure with preserved ejection fraction - coming to terms with an
      oxymoron.

PMID- 20047539
TI  - Lifelong consequences of poor fetal growth.

PMID- 20047540
TI  - Health care reform in the United States: an opportunity for primary care?

PMID- 20047541
TI  - Caveat anicula! Beware of quiet little old ladies: demographic features,
      pharmacotherapy, readmissions and survival in a 10-year cohort of patients with
      heart failure and preserved systolic function.
AB  - OBJECTIVE: To determine whether heart failure with preserved systolic function
      (HFPSF) has different natural history from left ventricular systolic dysfunction
      (LVSD). DESIGN AND SETTING: A retrospective analysis of 10 years of data (for
      patients admitted between 1 July 1994 and 30 June 2004, and with a study census
      date of 30 June 2005) routinely collected as part of clinical practice in a large
      tertiary referral hospital. MAIN OUTCOME MEASURES: Sociodemographic
      characteristics, diagnostic features, comorbid conditions, pharmacotherapies,
      readmission rates and survival. RESULTS: Of the 2961 patients admitted with
      chronic heart failure, 753 had echocardiograms available for this analysis. Of
      these, 189 (25%) had normal left ventricular size and systolic function. In
      comparison to patients with LVSD, those with HFPSF were more often female (62.4%
      v 38.5%; P = 0.001), had less social support, and were more likely to live in
      nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal
      impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and
      atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic
      heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to
      be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P =
      0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001).
      Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P =
      0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v
      2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912).
      CONCLUSIONS: Patients with HFPSF were predominantly older women with less social
      support and higher readmission rates for associated comorbid illnesses. We
      therefore propose that reduced survival in HFPSF may relate more to comorbid
      conditions than suboptimal cardiac management.

PMID- 20047542
TI  - Birthweight and natural deaths in a remote Australian Aboriginal community.
AB  - OBJECTIVES: To describe associations between birthweight and infant, child and
      early adult mortality from natural causes in a remote Australian Aboriginal
      community against a background of rapidly changing mortality due to better health
      services. DESIGN, PARTICIPANTS AND SETTING: Cohort study of 995 people with
      recorded birthweights who were born between 1956 and 1985 to an Aboriginal mother
      in a remote Australian Aboriginal community. Participants were followed through
      to the end of 2006. MAIN OUTCOME MEASURES: Rates of natural deaths of infants
      (aged 0 to < 1 year), children (aged 1 to < 15 years) and adults (aged 15 to < 37
      years), compared by birth intervals (1956-1965, 1966-1975 and 1976-1985 for
      infants and children, and 1956-1962 and 1963-1969 for adults) and by birthweight.
      RESULTS: Birthweights were low, but increased over time. Deaths among infants and
      children decreased dramatically over time, but deaths among adults did not. Lower
      birthweights were associated with higher mortality. Adjusted for birth interval,
      hazard ratios for deaths among infants, children and adults born at weights below
      their group birthweight medians were 2.30 (95% CI, 1.13-4.70), 1.78 (95% CI, 1.03
      3.07) and 3.49 (95% CI, 1.50-8.09), respectively. The associations were
      significant individually for deaths associated with diarrhoea in infants, with
      cardiovascular and renal disease in adults, and marginally significant for deaths
      from pulmonary causes in children and adults. CONCLUSION: The striking
      improvements in infant and child survival over time must be applauded. We
      confirmed a predisposing effect of lower birthweights on deaths in infants and
      children, and showed, for the first time, an association between lower
      birthweights and deaths in adults. Together, these factors are probably
      contributing to the current epidemic of chronic disease in Aboriginal people, an
      effect that will persist for decades. Similar phenomena are probably operating in
      developing countries.

PMID- 20047543
TI  - Role of general practitioners in managing age-related hearing loss.
AB  - OBJECTIVE: To assess the extent to which general practitioners in Australia are
      engaged in identifying age-related hearing loss and facilitating its management.
      DESIGN, SETTING AND PARTICIPANTS: Cross-sectional analysis of data collected
      between 1998 and 2000 from the Blue Mountains Hearing Study (BMHS), a
      representative population-based cohort of people aged >or= 50 years in two
      postcode areas west of Sydney. Also analysed were data collected between 2003 and
      2008 from random samples of Australian GPs who participated in the Bettering the
      Evaluation and Care of Health (BEACH) study, a national continuous cross
      sectional survey of GP activity. MAIN OUTCOME MEASURES: Rate of facilitating
      management and identification of hearing loss in older patients; content of GP
      patient encounters with hearing-impaired people; characteristics of participants
      seeking help from their GP. RESULTS: Of older people in the BMHS with measured
      (objective) bilateral hearing loss, about a third reported seeking help from
      their GP. BEACH survey data showed that only about 3 per 1,000 GP consultations
      with patients aged >or= 50 years involved management of age-related hearing loss.
      For every 100 age-related hearing problems managed, GPs undertook 12 procedural
      treatments, provided 20 referrals to specialists, and made 29 referrals to allied
      health professionals. CONCLUSION: In their routine consultations with patients,
      GPs have opportunities to identify hearing loss and appropriately refer patients
      to specialists or allied health professionals. Although GPs are responding to
      patient presentations for hearing loss, referring around 50% of cases, there
      appear to be relatively few cases in which hearing loss is identified
      opportunistically. Levels of identification and management of hearing loss by GPs
      in Australia are relatively low.

PMID- 20047544
TI  - Single-dose azithromycin versus seven days of amoxycillin in the treatment of
      acute otitis media in Aboriginal children (AATAAC): a double blind, randomised
      controlled trial.
AB  - OBJECTIVE: To compare the clinical effectiveness of single-dose azithromycin
      treatment with 7 days of amoxycillin treatment among Aboriginal children with
      acute otitis media (AOM) in rural and remote communities in the Northern
      Territory. DESIGN, SETTING AND PARTICIPANTS: Aboriginal children aged 6 months to
      6 years living in 16 rural and remote communities were screened for AOM. Those
      diagnosed with AOM were randomly allocated to receive either azithromycin (30
      mg/kg as a single dose) or amoxycillin (50mg/kg/day in two divided doses for a
      minimum of 7 days). We used a double-dummy method to ensure blinding. Our study
      was conducted from 24 March 2003 to 20 July 2005. MAIN OUTCOME MEASURES: Failure
      to cure AOM by the end of therapy; nasal carriage of Streptococcus pneumoniae and
      non-capsular Haemophilus influenzae (NCHi). RESULTS: We followed 306 of 320
      children (96%) allocated to the treatment groups. Single-dose azithromycin did
      not reduce (or increase) the risk of clinical failure (50% failure rate [82/165])
      compared with amoxycillin (54% failure rate [83/155]) (risk difference [RD], - 4%
      [95% CI, - 15% to 7%]; P = 0.504). Compared with amoxycillin, azithromycin
      significantly reduced the proportion of children with nasal carriage of S.
      pneumoniae (27% v 63%; RD, - 36% [95% CI, - 47% to - 26%]; P < 0.001) and NCHi
      (55% v 85%; RD, - 30% [95% CI, - 40% to - 21%]; P < 0.001). Nasal carriage of S.
      pneumoniae with intermediate or full resistance to penicillin was lower (but not
      significantly so) in the azithromycin group (10% v 16%), but this group had
      significantly increased carriage of azithromycin-resistant S. pneumoniae (10% v
      3%; RD, 7% [95% CI, 0.1% to 12%]; P = 0.001). Carriage of beta-lactamase
      producing NCHi was about 5% in both groups. CONCLUSION: Although azithromycin
      reduced nasal carriage of S. pneumoniae and NCHi, clinical failure was high in
      both treatment groups. The possibility of weekly azithromycin treatment in
      children with persistent AOM should be evaluated. TRIAL REGISTRATION: Australian
      Clinical Trials Registry ACTRN 12609000691246.

PMID- 20047545
TI  - A new model for neurology care in the emergency department.
AB  - OBJECTIVE: To assess the feasibility of using a rapid access neurology clinic to
      assess and manage patients considered safe to discharge home from the emergency
      department (ED), yet requiring specialist neurology review. DESIGN, SETTING AND
      PARTICIPANTS: The ED Rapid Access Neurology (ED RAN) clinic was trialled at Royal
      Prince Alfred Hospital, a major tertiary teaching hospital in Sydney, over a 12
      month period (23 March 2008 - 22 March 2009). The service uses a new clinic and
      referral system to offer suitable patients specialist neurology outpatient review
      within 5 working days of their discharge from the ED. MAIN OUTCOME MEASURES:
      Quality of patient care, patient satisfaction, estimated service impact on the
      hospital system. RESULTS: During the 12-month trial period, 311 patients were
      referred to the ED RAN clinic. Of these referrals, 222 patients (71%) attended
      the clinic, where a number of serious neurological diagnoses were made, and eight
      patients required admission after specialist review. All patients attending the
      clinic found the visit helpful. Consultant ED physicians believed that the clinic
      prevented 83 unnecessary admissions and 188 out-of-hours neurology registrar
      consultations, and saved an estimated 809 hours of ED bed time. CONCLUSIONS: The
      ED RAN clinic provides a viable model for improving the quality of patient care,
      with high levels of patient satisfaction. This model of care may allow
      significant cost savings and help to relieve the major access block in Australian
      EDs.

PMID- 20047546
TI  - Acceptance of pandemic (H1N1) 2009 influenza vaccination by the Australian
      public.
AB  - OBJECTIVE: To investigate the Australian public's expectations, concerns and
      willingness to accept vaccination with the pandemic (H1N1) 2009 influenza
      vaccine. DESIGN, SETTING AND PARTICIPANTS: A computer-assisted telephone
      interview survey was conducted between 20 August and 11 September 2009 by trained
      professional interviewers to study issues relating to vaccine uptake and
      perceived safety. The sample comprised 1155 randomly selected representative
      adults who had participated in a 2007 national study exploring knowledge and
      perceptions of pandemic influenza. MAIN OUTCOME MEASURES: Likely acceptance of
      pandemic (H1N1) 2009 vaccination, factors associated with acceptance, and
      respondents' willingness to share Australian vaccine with neighbouring developing
      countries. RESULTS: Of 1155 possible participants, 830 (72%) were successfully
      interviewed. Twenty per cent of the study group (169/830) reported that they had
      developed influenza-like symptoms during the 2009 pandemic period. Most
      respondents (645/830, 78%) considered pandemic (H1N1) 2009 to be a mild disease,
      and 211/830 (25%) regarded themselves as being at increased risk of infection.
      Willingness to accept pandemic (H1N1) 2009 vaccination was high (556/830, 67%)
      but was significantly lower than when pandemic vaccination uptake was
      investigated in 2007 (88%; P < 0.0001). Respondents who had already been
      vaccinated against seasonal influenza and those who perceived pandemic (H1N1)
      2009 to be severe were significantly more willing to accept vaccination. Most
      respondents (793/822, 96%) were willing to share surplus vaccine with developing
      countries in our region. CONCLUSION: Although two-thirds of Australian adults
      surveyed were willing to accept pandemic (H1N1) 2009 vaccination, and most
      supported sharing vaccine with developing countries, there is a need for
      accessible information on vaccine safety for those who are undecided about
      vaccination.

PMID- 20047547
TI  - Evidence-based guidelines for the management of hip fractures in older persons:
      an update.
AB  - OBJECTIVE: To update evidence-based guidelines for the treatment of proximal
      femoral fractures published in the Journal in 2003. DATA SOURCES: Systematic
      search of MEDLINE, CINAHL and EMBASE for articles published from October 2001 to
      June 2008, and the Cochrane Database of Systematic Reviews (most recent issue
      searched - Issue 2, 2008). STUDY SELECTION: Randomised controlled trials and meta
      analyses of all aspects of acute-care hospital treatment and rehabilitation for
      proximal femoral fractures among participants aged 50 years or older with
      proximal femoral fractures not associated with metastatic disease or multiple
      trauma. DATA EXTRACTION: All studies were reviewed independently by two
      assessors, who recorded individual study results, and an assessment of study
      quality and treatment conclusions was made according to Cochrane Collaboration
      protocols. If necessary, a third review was performed to reach consensus.
      RESULTS: 128 new studies were identified and 81 met our inclusion criteria.
      Recommendations for time to surgery, thromboprophylaxis, anaesthesia, analgesia,
      prophylactic antibiotics, surgical fixation of fractures, nutritional status,
      mobilisation and rehabilitation have been updated. Also, recommendations
      regarding surgical wound closure, management of postoperative delirium,
      osteoporosis treatment and hip protectors have been added. The guidelines include
      the current National Health and Medical Research Council grades of
      recommendations for clinical guidelines. CONCLUSIONS: Significant changes in
      recommendations have been made, particularly in relation to surgery,
      rehabilitation and tertiary prevention. Hip fracture should be treated according
      to the most up-to-date evidence to achieve the best possible outcomes and optimal
      use of limited resources.

PMID- 20047548
TI  - Myths of ideal hospital occupancy.
AB  - Significant problems in health care, such as access block and long waiting lists
      for elective surgery, have led to calls for keeping hospital occupancy at no more
      than 85%. It is elementary queueing theory that a finite-capacity system with
      variable demand cannot sustain both full utilisation and full availability.
      However, the statement that there is a single level of ideal or safe occupancy
      suitable for all situations is a simplistic interpretation and application of the
      underlying science. We argue that specific study and action are necessary to
      understand and deal with the problems of long waiting lists and access block in
      any given health care facility.

PMID- 20047549
TI  - High-functioning pervasive developmental disorders in adults.
AB  - High-functioning pervasive developmental disorders (PDDs) have only recently been
      widely recognised; they are diagnosed mainly in children. Key features are
      impaired social cognition and communication; obsessive interests, routines or
      activities; and social or occupational dysfunction. There are scant data about
      the prevalence of high-functioning PDDs in adults, and it is possible that many
      Australian adults with these conditions are undiagnosed. A specialist
      multidisciplinary approach is used for both children with PDDs and adults with
      other neuropsychiatric disabilities, and has the potential to help adults with
      high-functioning PDDs. Increased awareness and diagnosis of these conditions
      should not limit career or personal goals of individuals with PDDs but should aid
      them in finding happy and productive careers and lives.

PMID- 20047550
TI  - Spleen registry may help reduce the incidence of overwhelming postsplenectomy
      infection in Victoria.

PMID- 20047551
TI  - Persistent unilateral right diaphragmatic palsy following liver transplantation.

PMID- 20047552
TI  - The Australian Medical Council draft code of professional conduct: good practice
      or creeping authoritarianism? Comment.

PMID- 20047553
TI  - Use of selective serotonin reuptake inhibitors and suicidal ideation: findings
      from the 2007 National Survey of Mental Health and Wellbeing.

PMID- 20047554
TI  - Use of complementary and alternative medicine by patients with osteoporosis in
      Australia.

PMID- 20047555
TI  - Building capacity in medical education research in Australia.

PMID- 20047556
TI  - "Through a glass, darkly": the clinical and ethical implications of Munchausen
      syndrome. Comment.

PMID- 20047557
TI  - General practice: survival by adaptation.

PMID- 20047559
TI  - Cloning and functional characterization of pig CMP-N-acetylneuraminic acid
      hydroxylase for the synthesis of N-glycolylneuraminic acid as the xenoantigenic
      determinant in pig-human xenotransplantation.
AB  - In the present study, the pig CMP-N-acetylneuraminic acid hydroxylase gene
      (pcmah), a key enzyme for the synthesis of NeuGc (N-glycolylneuraminic acid), was
      cloned from pig small intestine and characterized. The ORF (open reading frame)
      of pcmah was 1734 bp, encoding 577 amino acids and consisting of 14 exons. Organ
      expression pattern analysis reveals that pcmah mRNA is mainly expressed in pig
      rectum, tongue, spleen and colon tissues, being the most highly expressed in
      small intestine. In the ectopic expression of pcmah, when pig kidney PK15 cells
      and human vascular endothelial ECV304 cells were transfected with the cloned
      pcmah, the NeuGc contents of these transfectants were greater in comparison with
      vector transfectants used as controls. In addition, in the functional analysis of
      NeuGc, HSMC (human-serum-mediated cytotoxicity) was elevated in the ectopic NeuGc
      expressing pcmah-transfected cells compared with controls. Moreover, binding of
      human IgM to the pcmah-transfected cells was significantly increased, whereas
      binding of IgG was slightly increased, indicating that the human IgM type was a
      major anti-NeuGc antibody. Furthermore, pcmah silencing by shRNA (short hairpin
      RNA) resulted in a decrease in NeuGc content and xenoantigenicity in PK15. From
      the results, it was concluded that the pcmah gene was capable of synthesizing the
      NeuGc acting as a xenoantigen in humans, confirming the NeuGc-mediated rejection
      response in pig-human xenotransplantation.

PMID- 20047560
TI  - Fenofibrate improves endothelial function in the brachial artery and forearm
      resistance arterioles of statin-treated Type 2 diabetic patients.
AB  - Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular
      disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these
      patients, residual risk remains high. Fenofibrate corrects atherogenic
      dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy
      lowers CVD risk. We investigated whether fenofibrate improves endothelial
      dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15
      statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)
      cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow
      mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145
      mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment
      periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated
      dilatation) were measured by ultrasonography at the start and end of each
      treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of
      microcirculatory endothelial function, and serum lipids, lipoproteins and apo
      (apolipoprotein) concentrations were also measured. Compared with placebo,
      fenofibrate increased FMD (mean absolute 2.1+/-0.6 compared with -0.3+/-0.6%,
      P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF
      {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100
      ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with -1.5
      (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols
      (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P < or = 0.03), but did
      not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in
      FMD was inversely associated with on-treatment LDL-cholesterol (r=-0.61, P=0.02)
      and apoB-100 (r=-0.54, P=0.04) concentrations. Fenofibrate improves endothelial
      dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to
      enhanced reduction in LDL-cholesterol and apoB-100 concentrations.

PMID- 20047561
TI  - Gene expression patterns of osteocyte-like MLO-Y4 cells in response to cyclic
      compressive force stimulation.
AB  - Although osteocytes have long been regarded as mechanosensors for translating
      mechanical signals into biochemical signals to regulate the other bone cells, the
      global gene expression patterns and pathways of osteocytes responding to
      mechanical stimulation are not well defined. We investigated CCF (cyclic
      compressive force) responsive gene expression patterns at different time-points
      using Mouse genome-wide oligonucleotide microarrays with an osteocyte-like MLO-Y4
      cell model. We performed a SOM (self-organizing maps) clustering algorithm based
      on pattern similarity to organize clusters of temporal expression patterns, and
      used qRT-PCR (quantitative reverse transcriptase PCR) analysis to validate
      expression patterns of selected genes. We also used functional and pathway
      analysis to evaluate the biological features of the data. In this study, we
      derived a biological hypothesis from the gene expression profiles that CCF
      triggers a tightly regulated transcriptional programme to induce bone resorption
      cell signalling and involves common pathways in osteocytes.

PMID- 20047562
TI  - Characterization of RNase HII substrate recognition using RNase HII-argonaute
      chimaeric enzymes from Pyrococcus furiosus.
AB  - RNase H (ribonuclease H) is an endonuclease that cleaves the RNA strand of RNA
      DNA duplexes. It has been reported that the three-dimensional structure of RNase
      H is similar to that of the PIWI domain of the Pyrococcus furiosus Ago
      (argonaute) protein, although the two enzymes share almost no similarity in their
      amino acid sequences. Eukaryotic Ago proteins are key components of the RNA
      induced silencing complex and are involved in microRNA or siRNA (small
      interfering RNA) recognition. In contrast, prokaryotic Ago proteins show greater
      affinity for RNA-DNA hybrids than for RNA-RNA hybrids. Interestingly, we found
      that wild-type Pf-RNase HII (P. furiosus, RNase HII) digests RNA-RNA duplexes in
      the presence of Mn2+ ions. To characterize the substrate specificity of Pf-RNase
      HII, we aligned the amino acid sequences of Pf-RNase HII and Pf-Ago, based on
      their protein secondary structures. We found that one of the conserved secondary
      structural regions (the fourth beta-sheet and the fifth alpha-helix of Pf-RNase
      HII) contains family-specific amino acid residues. Using a series of Pf-RNase HII
      Pf-Ago chimaeric mutants of the region, we discovered that residues Asp110,
      Arg113 and Phe114 are responsible for the dsRNA (double-stranded RNA) digestion
      activity of Pf-RNase HII. On the basis of the reported three-dimensional
      structure of Ph-RNase HII from Pyrococcus horikoshii, we built a three
      dimensional structural model of RNase HII complexed with its substrate, which
      suggests that these amino acids are located in the region that discriminates DNA
      from RNA in the non-substrate strand of the duplexes.

PMID- 20047563
TI  - Coping with multiple sclerosis: a 5-year follow-up study.
AB  - OBJECTIVES: To examine how coping styles among patients with multiple sclerosis
      (MS) change over time and how patients' coping styles after 5 years are
      associated with disability pension. MATERIALS AND METHODS: Seventy-six MS
      patients and 94 healthy controls were included in this study. The patients were
      examined at baseline and 5 years later. This included a neurological examination
      and information on disability pension and a questionnaire assessing coping (the
      COPE scale). Controls were registered at baseline only. RESULTS: Compared to
      healthy controls, MS patients were more passive in coping with disease related
      distress. This was even more pronounced 5 years later. Disability pensioned
      patients employed more social support, venting of emotions and behavioural
      disengagement at follow-up. CONCLUSION: This study shows that patients with MS
      employ coping styles that may be inadequate and this is not improved by adaption
      over time. Although patients also use strategies to enhance their lives, these
      findings suggest that there may be a potential for improving the lives of
      patients with MS through interventions that may enhance adequate coping with the
      disease.

PMID- 20047564
TI  - Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset
      seizures: a non-comparative, open-label study (ZEUS).
AB  - OBJECTIVES: To assess the efficacy and tolerability of zonisamide in a study
      allowing flexible dosing in a more diverse and less refractory population than
      assessed in randomized controlled trials. METHODS: This 19-week, non-comparative
      study of adjunctive zonisamide included 281 adults who had at least four partial
      onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to
      zonisamide doses were allowed after titration, except during two fixed-dose
      periods (weeks 10-13 and 16-19). RESULTS: At the end of the second fixed-dose
      period (median dose 300 mg/day), the median reduction in monthly seizure
      frequency was 33.3-41.1%; > or =50% responder rate was 40.9-44.2%; and seizure
      freedom rate was 15.0-15.9%, depending on the analysis used. The most common
      adverse events were fatigue (16.7%) and somnolence (15.3%). CONCLUSIONS:
      Zonisamide demonstrated efficacy in a setting more reflective of clinical
      practice and was generally well tolerated.

PMID- 20047565
TI  - Quantitative diffusion tensor imaging for evaluation of motor function in
      patients with brain infarcts.
AB  - OBJECTIVE: To evaluate the quantitative diffusion value in ipsilateral cerebral
      peduncle of patients with differing motor function abilities and analyse the
      thresholds discriminating the poor motor function disability. METHOD: Twenty-nine
      patients who previously suffered stroke underwent diffusion tensor imaging
      examinations. Motor function was evaluated 8 months after the event. The
      ipsilateral apparent diffusion coefficient (ADC) and fractional anisotropy (FA)
      of cerebral peduncle and ADC ratio and FA ratio of patients with different motor
      function scales were analysed. RESULTS: The ipsilateral FA value and FA ratio
      were distinctly different in patients with different motor function scales, and
      significantly correlated with the motor function scales. There was no significant
      difference of ipsilateral ADC and ADC ratio, and neither had correlation with
      motor function scale. The patients with poor motor function scale could be
      discriminated by the cutoff value of ipsilateral FA of 0.453 and FA ratio of
      0.623 with sensitivity of 90%, 75% and specificity of 88.9%, 88.9% respectively.
      CONCLUSIONS: The ipsilateral FA value and FA ratio were feasible and better
      imaging indices in discriminating patients with poor motor function ability.

PMID- 20047566
TI  - Serum adiponectin acutely after an ischemic stroke: implications for a long
      lasting, suppressed anti-inflammatory role.
AB  - OBJECTIVE: Past ischemic stroke (IS) patients display suppressed adiponectin
      (ADPN) levels a few months after disease onset. It is still unclear whether
      hypoadiponectinemia is already present by the early stages of stroke or occurs as
      a delayed effect of the acute ischemic reaction. In the present study we
      investigated ADPN levels acutely after an IS. MATERIALS AND METHODS: Serum ADPN
      was measured in 82 consecutive acute IS patients, and 30 stroke-free subjects of
      similar age and sex distributions. RESULTS: Patients had significantly lower ADPN
      levels than controls. Higher ADPN was significantly associated with reduced odds
      for IS accounting for age, sex and high-density lipoproteins. This association
      was strengthened after further adjustments for potential confounders. ADPN levels
      remained suppressed even 6 months after stroke. CONCLUSIONS: ADPN is
      significantly suppressed already by the early phases of stroke, and remains
      unchanged 6 months later. We propose a stable-over-time anti-inflammatory role of
      ADPN in IS, unrelated to the acute ischemic reaction.

PMID- 20047567
TI  - Autonomic dysfunction in presymptomatic and early symptomatic Huntington's
      disease.
AB  - OBJECTIVES: Although autonomic dysfunction was found in advanced Huntington's
      disease (HD) patients it is not clear whether there is autonomic dysfunction in
      presymptomatic and early symptomatic HD. MATERIAL & METHODS: Different
      cardiovascular autonomic tests were performed in 14 presymptomatic HD mutation
      carriers (PHD), 11 early symptomatic HD patients (EHD) and in 25 sex and age
      matched controls. RESULTS: We found attenuated response to simple mental
      arithmetic test (relative heart rate in PHD and EHD was 10% lower than in
      controls; diastolic pressure was 10.6% lower in EHD than in controls; P < 0.05)
      and exaggerated response to the late phase of cold pressor test (relative heart
      rate was 10% higher in PHD and 7% higher in EHD than in controls; P < 0.05). The
      rest of the cardiovascular autonomic tests did not reveal significant differences
      between patients and controls. CONCLUSIONS: Our results suggest that subtle
      autonomic dysfunction occurs even in PHD and EHD.

PMID- 20047568
TI  - Whole-body high-field MRI shows no skeletal muscle degeneration in young patients
      with recessive myotonia congenita.
AB  - BACKGROUND: Muscle magnetic resonance imaging (MRI) is the most sensitive method
      in the detection of dystrophic and non-dystrophic abnormalities within striated
      muscles. We hypothesized that in severe myotonia congenita type Becker muscle
      stiffness, prolonged transient weakness and muscle hypertrophy might finally
      result in morphologic skeletal muscle alterations reflected by MRI signal
      changes. AIM OF THE STUDY: To assess dystrophic and/or non-dystrophic alterations
      such as fatty or connective tissue replacement and muscle edema in patients with
      severe recessive myotonia congenita. METHODS: We studied three seriously affected
      patients with myotonia congenita type Becker using multisequence whole-body high
      field MRI. All patients had molecular genetic testing of the muscle chloride
      channel gene (CLCN1). RESULTS: Molecular genetic analyses demonstrated recessive
      CLCN1 mutations in all patients. Two related patients were compound heterozygous
      for two novel CLCN1 mutations, Q160H and L657P. None of the patients showed
      skeletal muscle signal changes indicative of fatty muscle degeneration or edema.
      Two patients showed muscle bulk hypertrophy of thighs and calves in line with the
      clinical appearance. CONCLUSIONS: We conclude that (i) chloride channel
      dysfunction alone does not result in skeletal muscle morphologic changes even in
      advanced stages of myotonia congenita, and (ii) MRI skeletal muscle alterations
      in myotonic dystrophy must be clear consequences of the dystrophic disease
      process.

PMID- 20047569
TI  - A relationship between migraine and biliary tract disorders: findings in two
      Swedish samples of elderly twins.
AB  - OBJECTIVES: To investigate whether there is a relationship between the clinical
      occurrence of migraine and biliary tract disorders (BTD) and to study whether
      there is a genetic influence on such an association. MATERIALS AND METHODS: The
      near lifetime morbidity for migraine and BTD was examined in two Swedish twin
      samples: OCTO-Twin (149 MZ and 202 DZ pairs; 234 men, 468 women; 80 years of age
      or older at inclusion), and the GENDER study (249 unlike-sex DZ-pairs; 70-80
      years of age at inclusion). The diagnosis of BTD was established by perusal of
      medical records from the last twenty years. The diagnosis of migraine was based
      on iterated questionnaires and personal interviews. RESULTS: The odds ratio (OR)
      of BTD among OCTO-Twin subjects suffering from migraine was 3.5 (1.9-6.7) in
      monozygotic pairs and 1.7 (1.0-2.9) in dizygotic pairs The corresponding figures
      among the GENDER unlike-sex DZ-pairs was 2.7 (1.6-4.5). Migraine was associated
      with female sex and waist circumference. CONCLUSIONS: There is a relationship
      between the occurrence of migraine and BTD, also when controlling for the fact
      that both disorders are more frequent in women. The association appears to be
      partly attributable to genetic influences.

PMID- 20047570
TI  - Computerized cognition assessment during acetylcholinesterase inhibitor treatment
      in Alzheimer's disease.
AB  - OBJECTIVES: Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog)
      has become a standard clinical trials outcome for cognition, but has been
      recognized as deficient in areas including coverage of cognitive domains,
      sensitivity and standardization. Computerized test batteries may address some of
      these issues. The cognitive drug research computerized assessment (CDR) system is
      validated in Alzheimer's disease (AD). This study was designed to further
      evaluate validity in relation to ADAS-Cog, mini mental state examination (MMSE)
      and cerebrospinal fluid (CSF) biomarkers and psychometric properties, in a
      population of Alzheimer's patients on stable anticholinesterase treatment.
      MATERIALS AND METHODS: Patients completed cognition assessments, CSF and blood
      sampling at baseline and 6 months later. Data for 65 patients were evaluated.
      RESULTS: The CDR system demonstrated good psychometric properties in this
      population. Measures of psychomotor speed showed possible sensitivity to decline
      over 6 months. CONCLUSIONS: There are a number of methodological problems with
      current cognition assessment methodology for clinical trials. Computerized
      measures and in particular millisecond reaction time measures, may address many
      of these issues.

PMID- 20047571
TI  - Statin treatment after a recent TIA or stroke: is effectiveness shown in
      randomized clinical trials also observed in everyday clinical practice?
AB  - AIM AND BACKGROUND: The benefit of statin treatment in patients with a previous
      ischemic stroke or transient ischemic attack (TIA) has been demonstrated in
      randomized clinical trials (RCT). However, the effectiveness in everyday clinical
      practice may be decreased because of a different patient population and less
      controlled setting. We aim to describe statin use in an unselected cohort of
      patients, identify factors related to statin use and test whether the effect of
      statins on recurrent vascular events and mortality observed in RCTs is also
      observed in everyday clinical practice. METHODS: In 10 centers in the
      Netherlands, patients admitted to the hospital or visiting the outpatient clinic
      with a recent TIA or ischemic stroke were prospectively and consecutively
      enrolled between October 2002 and May 2003. Statin use was determined at
      discharge and during follow-up. We used logistic regression models to estimate
      the effect of statins on the occurrence of vascular events (stroke or myocardial
      infarction) and mortality within 3 years. We adjusted for confounders with a
      propensity score that relates patient characteristics to the probability of using
      statins. RESULTS: Of the 751 patients in the study, 252 (34%) experienced a
      vascular event within 3 years. Age, elevated cholesterol levels and other
      cardiovascular risk factors were associated with statin use at discharge. After 3
      years, 109 of 280 (39%) of the users at discharge had stopped using statins.
      Propensity score adjusted analyses showed a beneficial effect of statins on the
      occurrence of the primary outcome (odds ratio 0.8, 95% CI: 0.6-1.2). CONCLUSION:
      In our study, we found poor treatment adherence to statins. Nevertheless, after
      adjustment for the differences between statin users and non-statin users, the
      observed beneficial effect of statins on the occurrence of vascular events within
      3 years, although not statistically significant, is compatible with the effect
      observed in clinical trials.

PMID- 20047572
TI  - Pharmacokinetic interaction study between eslicarbazepine acetate and lamotrigine
      in healthy subjects.
AB  - OBJECTIVE: Anti-epileptic drugs are often used in combination. Both
      eslicarbazepine (main metabolite of eslicarbazepine acetate, ESL) and lamotrigine
      undergo conjugation with glucuronic acid, and both eslicarbazepine and its
      glucuronide and lamotrigine glucuronide undergo extensive renal elimination;
      therefore, there is a potential for interaction. This study investigated the
      interaction between ESL and lamotrigine in healthy subjects. METHODS: Open-label
      study in two parallel groups of 16 healthy volunteers each. After an 8-day
      treatment with ESL or lamotrigine, ESL (1200 mg once-daily) and lamotrigine (150
      mg once-daily) were co-administered for 19 days. Geometric mean ratios (GMR) and
      90% confidence intervals (90% CI) for maximum plasma concentration (C(max)) and
      area under the plasma concentration-time curve in the dosing interval (AUC(0-24))
      were calculated for eslicarbazepine (ESL active metabolite) and lamotrigine.
      RESULTS: The C(max) and AUC(0-24) GMR (90% CI) were, respectively, 95% (87-102%)
      and 96% (91-102%) for eslicarbazepine, and 88% (82-94%) and 86% (81-92%) for
      lamotrigine. The 90% CI of the C(max) and AUC(0-24) GMR fell within the
      prespecified acceptance interval (80-125%) both for eslicarbazepine and
      lamotrigine. CONCLUSION: There was no significant pharmacokinetic interaction
      between ESL and lamotrigine in healthy subjects. Therefore, no dosage adjustment
      appears to be usually required in either lamotrigine or ESL when the drugs are co
      administered.

PMID- 20047573
TI  - The socio-economical burden of hypersomnia.
AB  - OBJECTIVES: In the absence of socio-economical consequences of hypersomnia this
      study addresses the factual indirect and direct costs. METHODS: Two thousand two
      hundred and eight patients with a hypersomnia diagnosis from 1998 to 2005 were
      identified in the Danish national patient registry (NPR), each compared with 4
      age and gender adjusted, randomly chosen citizens selected from the Civil
      Registration System Statistics. The health cost was decomposed in direct and
      indirect yearly costs, including labor supply and social transfer payments.
      Direct costs included frequencies and costs of discharges and outpatient use by
      cost weights according to diagnosis related groups and specific outpatient prices
      based on data from The Danish Ministry of Health. The use of and costs of drugs
      was based on data from the Danish Medicines Agency. The frequencies and costs
      from primary sectors were based on data from The National Health Security.
      Indirect costs were based on income data from the coherent social statistics
      (CSS). RESULTS: Patients with hypersomnia presented significant higher health
      related contact rate, expenses and medication use. No differences were identified
      in employment and income. The yearly sum of direct and indirect costs were yearly
      euro3402 vs. euro1212 in controls (P < 0.001), corresponding to a yearly excess
      costs euro2190. The patients presented higher transfer income, total euro889.
      CONCLUSION: Hypersomnia patient present higher health and medication uses, and
      social transfer income and thus represent a significant socio-economical burden.

PMID- 20047575
TI  - SIRT6 protects against pathological damage caused by diet-induced obesity.
AB  - The NAD+-dependent SIRT6 deacetylase is a therapeutic candidate against the
      emerging metabolic syndrome epidemic. SIRT6, whose deficiency in mice results in
      premature aging phenotypes and metabolic defects, was implicated in a calorie
      restriction response that showed an opposite set of phenotypes from the metabolic
      syndrome. To explore the role of SIRT6 in metabolic stress, wild type and
      transgenic (TG) mice overexpressing SIRT6 were fed a high fat diet. In comparison
      to their wild-type littermates, SIRT6 TG mice accumulated significantly less
      visceral fat, LDL-cholesterol, and triglycerides. TG mice displayed enhanced
      glucose tolerance along with increased glucose-stimulated insulin secretion. Gene
      expression analysis of adipose tissue revealed that the positive effect of SIRT6
      overexpression is associated with down regulation of a selective set of
      peroxisome proliferator-activated receptor-responsive genes, and genes associated
      with lipid storage, such as angiopoietin-like protein 4, adipocyte fatty acid
      binding protein, and diacylglycerol acyltransferase 1, which were suggested as
      potential targets for drugs to control metabolic syndrome. These results
      demonstrate a protective role for SIRT6 against the metabolic consequences of
      diet-induced obesity and suggest a potentially beneficial effect of SIRT6
      activation on age-related metabolic diseases.

PMID- 20047574
TI  - Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity,
      hydration, and strength in aged mice.
AB  - Aging or glucocorticoid excess decrease bone strength more than bone mass in
      humans and mice, but an explanation for this mismatch remains elusive. We report
      that aging in C57BL/6 mice was associated with an increase in adrenal production
      of glucocorticoids as well as bone expression of 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) type 1, the enzyme that activates glucocorticoids.
      Aging also decreased the volume of the bone vasculature and solute transport from
      the peripheral circulation to the lacunar-canalicular system. The same changes
      were reproduced by pharmacologic hyperglucocorticoidism. Furthermore, mice in
      which osteoblasts and osteocytes were shielded from glucocorticoids via cell
      specific transgenic expression of 11beta-HSD type 2, the enzyme that inactivates
      glucocorticoids, were protected from the adverse effects of aging on osteoblast
      and osteocyte apoptosis, bone formation rate and microarchitecture,
      crystallinity, vasculature volume, interstitial fluid, and strength. In addition,
      glucocorticoids suppressed angiogenesis in fetal metatarsals and hypoxia
      inducible factor-1alpha transcription and vascular endothelial growth factor
      production in osteoblasts and osteocytes. These results, together with the
      evidence that dehydration of bone decreases strength, reveal that endogenous
      glucocorticoids increase skeletal fragility in old age as a result of cell
      autonomous effects on osteoblasts and osteocytes leading to interconnected
      decrements in bone angiogenesis, vasculature volume, and osteocyte-lacunar
      canalicular fluid.

PMID- 20047577
TI  - Proton pump inhibitors as a risk factor for paediatric Clostridium difficile
      infection.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs)
      may play an important role on the onset of Clostridium difficile-associated
      disease (CDAD) in adults. The impact of Clostridium difficile on children treated
      with gastric acid-suppressing agents remains unknown. AIM: To investigate the
      relationship between CDAD and exposure to acid suppressive therapy in
      hospitalized paediatric patients. METHODS: We reviewed the medical records of
      children, with a diagnosis of protracted diarrhoea and abdominal pain, whose
      stool was analysed for C. difficile toxins. We identified 68 patients with CDAD.
      For each patient, we randomly selected one control subjects with stool analysis
      negative for C. difficile. Comorbid illnesses, previous hospitalizations,
      antibiotics, corticosteroids, immunosuppressants and gastric acid suppressing
      exposures were recorded. RESULTS: The use of PPI was significantly higher in C.
      difficile positive group compared with C. difficile negative group [odds ratio
      (OR): = 4.5; 95% confidence interval (CI) = 1.4-14.4]. We also found a trend for
      the use of H(2)RAs in patients infected by C. difficile compared with C.
      difficile negative comparison group (OR: = 3.8; 95% CI = 0.7-18.9). CONCLUSIONS:
      Children exposed to PPIs therapy seem to be at higher risk for the development of
      Clostridium difficile-associated disease.

PMID- 20047578
TI  - Clinical and economic outcomes in a population-based European cohort of 948
      ulcerative colitis and Crohn's disease patients by Markov analysis.
AB  - BACKGROUND: Forecasting clinical and economic outcomes in ulcerative colitis (UC)
      and Crohn's disease (CD) patients is complex, but necessary. AIMS: To determine:
      the frequency of treatment-classified clinical states; the probability of
      transition between states; and the economic outcomes. METHODS: Newly diagnosed UC
      and CD patients, allocated into seven clinical states by medical and surgical
      treatments recorded in serial 3-month cycles, underwent Markov analysis. RESULTS:
      Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most
      frequent clinical outcomes were medical/surgical remission (medication-free) and
      mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids),
      comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively.
      The probability of drug-response in patients receiving systemic
      corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had
      similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery
      was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes,
      surgery was costlier in UC per cycle, but the outlay over 10 years was greater in
      CD. Drug-refractory UC and CD cases engendered high costs in the cohort.
      CONCLUSIONS: Most patients on 5-aminosalicylates, corticosteroids and
      immunomodulators had favourable clinical and economic outcomes over 10 years.
      Drug-refractory and surgical patients exhibited greater long-term expenses.

PMID- 20047579
TI  - Natural history of Crohn's disease in patients who underwent intentional
      restorative proctocolectomy with ileal pouch-anal anastomosis.
AB  - BACKGROUND: Crohn's disease is generally considered a relative contraindication
      for restorative proctocolectomy with ileal pouch anastomosis (IPAA). The natural
      history of IPAA in these patients has not well been defined. AIM: To evaluate the
      natural history of IPAA in patients with a well-defined preoperative Crohn's
      disease. METHODS: All patients from the Pouchitis Clinic who had a preoperative
      diagnosis of Crohn's disease were screened and 11 patients met the inclusion
      criteria. The control group (with a 1:4 ratio) consisted of IPAA patients with a
      preoperative diagnosis of UC. RESULTS: During the follow-up period of 5.0 years,
      7 of 11 (63.6%) with a preoperative diagnosis of Crohn's disease developed
      Crohn's disease of the pouch. Crohn's disease of the pouch developed 0.2-15 years
      after ileostomy closure. The remaining four patients with a preoperative
      diagnosis of Crohn's disease did not demonstrate signs of Crohn's disease in 2,
      11, 11 and 24 years after pouch surgery, respectively. CONCLUSIONS: Post
      operative development of Crohn's disease of the pouch was common in patients with
      a preoperative diagnosis of Crohn's disease who underwent IPAA. Long-term medical
      therapy was often required. Large multi-centre studies are warranted to delineate
      further the natural history of the disease, before Crohn's disease is considered
      an indication for IPAA.

PMID- 20047580
TI  - Childhood coeliac disease: towards an improved serological mass screening
      strategy.
AB  - BACKGROUND: In 1997-1998, 6127 asymptomatic children aged 2-4 years were screened
      for coeliac disease (CD) by anti-endomysium (EmA) testing in the Netherlands.
      After 6 (+/-2) months, biopsies were performed in 57 seropositive children;
      31(54%) had villous atrophy, but 26 (46%), all HLA-DQ2/DQ8 positive, had normal
      histology. AIMS: To reduce the number of unnecessary biopsies after serological
      mass screening for CD in asymptomatic young children by optimizing screening
      procedures. METHODS: Comparing different tests and optimizing their cut-off
      point: screening samples were tested for EmA, tissue-transglutaminase (tTGA),
      antigliadin and deamidated-gliadin-peptides (anti-DGP) antibodies. Determining
      serological persistence over time: persistence of EmA and tTGA was determined by
      testing serological samples obtained at biopsy. RESULTS: Tissue-transglutaminase
      and anti-DGP correlated with EmA. Optimization of standard cut-off points not
      only reduced unnecessary biopsies by 50-96% but also reduced sensitivity. EmA
      persisted in all CD children, but in only 50% of the non-CD children. tTGA
      persisted in 83% of CD, but in only 15% of non-CD children. CONCLUSIONS: Coeliac
      disease antibodies may be present transiently in genetically predisposed
      children. To avoid unnecessary biopsies, serological mass screening procedures
      may be improved by repeating EmA and/or tTGA in initially seropositive young
      children after 6 months, before proceeding to biopsy. This may reduce the number
      of unnecessary biopsies that are performed.

PMID- 20047581
TI  - The response of Crohn's strictures to endoscopic balloon dilation.
AB  - BACKGROUND: Endoscopic balloon dilation has been shown to be an alternative to
      surgery in the treatment of Crohn's symptomatic strictures. AIM: To analyse the
      impact of the type of the strictures -de novo or anastomotic - their location and
      their length on the outcome of endoscopic balloon dilation. METHODS: Between
      December 1999 and June 2008, 55 patients underwent 93 balloon dilations for 74
      symptomatic strictures. One stricture was located in the duodenum, 39 strictures
      were in the terminal ileum, 17 at the ileocoecal anastomosis after a preceding
      resection and 17 in the colon. RESULTS: Endoscopic treatment was successful in
      76% of the patients during an observation period of 44 (1-103) months. Of the
      patients, 24% required surgery. All patients who underwent surgery had de novo
      strictures in the terminal ileum. These strictures were significantly longer
      compared with the ileal strictures that responded to endoscopic treatment [7.5 (1
      25) cm vs. 2.5 (1-25) cm; P = 0.006]. CONCLUSIONS: The long-term success of
      endoscopic balloon dilation depends on the type of the strictures, their location
      and their length. Failure of endoscopic treatment was observed only in long
      segment strictures in the terminal ileum.

PMID- 20047582
TI  - Some severe maternal diseases might be caused by fetal-versus-maternal disease
      (FVMD).
AB  - Pregnancy-related disease is a common challenging clinical problem. From our
      review and clinical experience, we hypothesize that many severe pregnancy-related
      complications might be caused by a fetal-versus-maternal disease (FVMD), based on
      the fact that maternal disease is related to immunity and that fetal cells are
      present in maternal blood. Fetus is a semi-antigen and can be considered as a
      tumor or graft. The pathophysiology of FVMD must be complex. We speculate it to
      be a three-step process: impaired maternal immunological function, fetal T-cell
      activation and injury of target organs. More experiments and research will be
      needed to prove our hypothesis.

PMID- 20047583
TI  - Role of inflammatory cytokines and eNOS gene polymorphism in pathophysiology of
      pre-eclampsia.
AB  - PROBLEM: Pre-eclampsia involves endothelial vascular dysfunction. The aim of this
      study was to test the hypothesis that (i) endothelial nitric oxide (NO) synthase
      Glu298Asp gene polymorphism limits constitutive NO production causing endothelial
      dysfunction and (ii) inflammatory cytokines impairs endothelium dependent
      relaxation in pre-eclampsia. METHOD OF STUDY: This cross-sectional study included
      50 women with pre-eclampsia and 50 healthy pregnant women. Their blood samples
      were analyzed for NO, inflammatory cytokines and endothelial NO synthase (eNOS)
      gene polymorphism. RESULT: Decreased NO levels whereas increased tumor necrosis
      factor-alpha, interleukin (IL)-6 and interleukin-2 were found in pre-eclampsia (P
      < 0.001). No significant differences were found in genotype/allele distribution
      between two groups. Significant negative correlation was observed between NO and
      IL-6 in pre-eclamptic group (P = 0.001). CONCLUSION: An IL-6-mediated endothelium
      dependent NO-cyclic guanine monophosphate-mediated relaxation pathway may be
      inhibited in systemic vessels in pre-eclampsia. As observed in this study
      Glu298Asp eNOS gene polymorphism did not showed significant association with pre
      eclampsia.

PMID- 20047584
TI  - No association between the GSTP1 exon 5 polymorphism and susceptibility to
      advanced stage endometriosis in the Korean population.
AB  - PROBLEM: To investigate whether the glutathione-S-transferase P1 (GSTP1) exon 5
      polymorphism is associated with susceptibility to advanced stage endometriosis in
      Korean women. METHOD OF STUDY: Case-control study in a collective of 260 patients
      and 164 controls. Genotyping of the GSTP1 exon 5 polymorphism was performed by
      using real-time TaqMan PCR assay. RESULTS: The genotype distribution of the GSTP1
      exon 5 polymorphism in the endometriosis group was not significantly different
      from that of the control group (AA/AG/GG rates were 64.2%/32.7%/3.1% and
      65.2%/31.7%/3.0% for the endometriosis and control groups, respectively, P =
      0.977). Further subgroup analysis according to either stage or bilaterality of
      ovarian endometrioma also found no significant difference in the genotype
      distribution between any of the endometriosis subgroups and the control group.
      CONCLUSION: These findings suggest that the GSTP1 exon 5 polymorphism is not a
      major determinant of the development of advanced stage endometriosis in the
      Korean population.

PMID- 20047585
TI  - Leptin on peritoneal macrophages of patients with endometriosis.
AB  - PROBLEM: The expression of cyclooxygenase (COX)-2 is considered as a marker of
      macrophage activation and has been implicated in the development of
      endometriosis. Leptin is an immunomodulator, which may also affect the
      development of endometriosis. However, how leptin contributes to these
      pathological processes has not been completely understood. The aim of this study
      was to investigate the effects of leptin on peritoneal macrophages and its
      relationship with endometriosis. METHODS OF STUDY: Peritoneal fluid from 60 women
      of reproductive age was obtained while they underwent laparoscopy. Forty patients
      had endometriosis and 20 patients did not have endometriosis. The concentration
      of leptin in the peritoneal fluid and prostaglandin F(2alpha) levels was measured
      by ELISA, and the other protein expression using Western blot when peritoneal
      macrophages were stimulated with leptin. RESULTS: Concentration of leptin in
      peritoneal fluid was increased in patients with endometriosis compared with
      disease-free normal control. Functional leptin receptor was present in peritoneal
      macrophages. Treatment of peritoneal macrophages with leptin induced COX-2
      expression. Production of prostaglandin F(2alpha) by peritoneal macrophages was
      increased after leptin stimulation in women with endometriosis. CONCLUSION:
      Elevated concentration of leptin in peritoneal fluid may contribute to the
      pathological process of endometriosis through activation of peritoneal
      macrophages.

PMID- 20047586
TI  - Role of regulatory and angiogenic cytokines in invasion of trophoblastic cells.
AB  - PROBLEM: Trophoblast invasion is a temporally and locally restricted process,
      which regulates implantation and oxygen arrival to the embryo through the dialog
      with spiral artery endothelium. Trophoblast factors with angiogenic potential are
      activated by hypoxia. Their capacities to induce proliferation, migration, and
      invasion of trophoblastic cells have been investigated. METHOD OF STUDY: The
      expression of interleukin (IL)-6, CD126, CD130, vascular endothelial growth
      factor (VEGF), and hypoxia inducible factor-1alpha (HIF-1alpha) has been silenced
      in JEG-3 choriocarcinoma cells by using siRNA. Silencing efficacy has been
      assessed by ELISA, PCR or Western blotting. Proliferation has been measured by
      flow cytometry, migration by a transwell assay, and invasion by a Matrigel assay.
      RESULTS: Proliferation was significantly reduced by silencing of CD126 or CD130,
      migration by silencing of IL-6, VEGF, or HIF-1alpha, and invasion by silencing of
      IL-6 and HIF-1alpha. CONCLUSION: The expression of IL-6, VEGF, and HIF-1alpha in
      trophoblastic cells is involved in the control of trophoblast invasion and
      migration.

PMID- 20047587
TI  - Procreative beneficence: cui bono?
AB  - Recently, Julian Savulescu and Guy Kahane have defended the Principle of
      Procreative Beneficence (PB), according to which prospective parents ought to
      select children with the view that their future child has 'the best chance of the
      best life'. I argue that the arguments Savulescu and Kahane adduce in favour of
      PB equally well support what I call the Principle of General Procreative
      Beneficence (GPB). GPB states that couples ought to select children in view of
      maximizing the overall expected value in the world, not just the welfare of their
      future child. I further argue that Savulescu and Kahane's claim that PB has
      significantly more weight than competing moral principles, such as GPB, lacks
      justification. A possible argument for PB having significant weight builds on a
      principle of parental partiality towards one's own children. But this principle
      does not support PB; it supports a Principle of Sibling-Oriented Procreative
      Beneficence (SPB), according to which parents selecting a child should maximize
      the benefit of all their children. Indeed, PB itself will in some cases be self
      effacing in favour of SPB.

PMID- 20047588
TI  - Competence, practical rationality and what a patient values.
AB  - According to the principle of patient autonomy, patients have the right to be
      self-determining in decisions about their own medical care, which includes the
      right to refuse treatment. However, a treatment refusal may legitimately be
      overridden in cases where the decision is judged to be incompetent. It has
      recently been proposed that in assessments of competence, attention should be
      paid to the evaluative judgments that guide patients' treatment decisions. In
      this paper I examine this claim in light of theories of practical rationality,
      focusing on the difficult case of an anorexic person who is judged to be
      competent and refuses treatment, thereby putting themselves at risk of serious
      harm. I argue that the standard criteria for competence assess whether a
      treatment decision satisfies the goals of practical decision-making, and that
      this same criterion can be applied to a patient's decision-guiding commitments.
      As a consequence I propose that a particular understanding of practical
      rationality offers a theoretical framework for justifying involuntary treatment
      in the anorexia case.

PMID- 20047589
TI  - Predictive testing and existential absurdity: resonances between experiences
      around genetic diagnosis and the philosophy of Albert Camus.
AB  - Predictive genetic testing may confront those affected with difficult life
      situations that they have not experienced before. These life situations may be
      interpreted as 'absurd'. In this paper we present a case study of a predictive
      test situation, showing the perspective of a woman going through the process of
      deciding for or against taking the test, and struggling with feelings of
      alienation. To interpret her experiences, we refer to the concept of absurdity,
      developed by the French Philosopher Albert Camus. Camus' writings on absurdity
      appear to resonate with patients' stories when they talk about their body and
      experiences of illness. In this paper we draw on Camus' philosophical essay 'The
      Myth of Sisyphus' (1942), and compare the absurd experiences of Sisyphus with the
      interviewee's story. This comparison opens up a field of ethical reflection. We
      demonstrate that Camus' concept of absurdity offers a new and promising approach
      to understanding the fragility of patients' situations, especially in the field
      of predictive testing. We show that people affected might find new meaning
      through narratives that help them to reconstruct the absurd without totally
      overcoming it. In conclusion, we will draw out some normative consequences of our
      narrative approach.

PMID- 20047590
TI  - The contributions of empirical evidence to socio-ethical debates on fresh embryo
      donation for human embryonic stem cell research.
AB  - This article is a response to McLeod and Baylis (2007) who speculate on the
      dangers of requesting fresh 'spare' embryos from IVF patients for human embryonic
      stem cell (hESC) research, particularly when those embryos are good enough to be
      transferred back to the woman. They argue that these embryos should be frozen
      instead. We explore what is meant by 'spare' embryos. We then provide empirical
      evidence, from a study of embryo donation and of embryo donors' views, to
      substantiate some of their speculations about the problems associated with
      requesting fresh embryos. However, we also question whether such problems are
      resolved by embryo freezing, since further empirical evidence suggests that this
      raises other social and ethical problems for patients. There is little evidence
      that the request for embryos for research, in itself, causes patients distress.
      We suggest, however, that no requests for fresh embryos should be made in the
      first cycle of IVF treatment. Deferring the request to a later cycle ensures that
      potential donors are better informed (by experience and reflection) about the
      possible destinations of their embryos and about the definition of 'spare
      embryos'. Both this article, and that by McLeod and Baylis, emphasize the need to
      consider the views and experiences of embryo donors when evaluating the ethics of
      embryo donation for hESC research.

PMID- 20047591
TI  - Annexin II promotes invasion and migration of human hepatocellular carcinoma
      cells in vitro via its interaction with HAb18G/CD147.
AB  - HAb18G/CD147, a member of the immunoglobulin family enriched on the surface of
      tumor cells, is reported to be correlated with invasion, metastasis, growth, and
      survival of malignant cells. Here, we found that annexin II, a 36-kDa Ca(2+)- and
      phospholipid-binding protein and in vivo substrate for tyrosine kinase and PKC,
      is a new interaction protein of HAb18G/CD147 in human hepatocellular carcinoma
      (HCC) cells. In the present study, we explored the unclear role of annxin II in
      HCC invasion and migration and the interaction effects between HAb18G/CD147 and
      annexin II. Our data show that downregulation of annexin II in HCC cells
      significantly decreased the secretion of MMP, migration ability, and invasive
      potential, and affected the cytoskeleton rearrangement of tumor cells. The MMP-2
      level and invasive potential of HCC cells were regulated by both annexin II and
      HAb18G/CD147. Also, interaction effects exist between the two molecules in tumor
      progression, including MMP-2 production, migration, and invasion. These results
      suggest that annexin II promotes the invasion and migration of HCC cells in
      vitro, and annexin II and HAb18G/CD147 interact with each other in the same
      signal transduction pathway working as a functional complex in tumor progression.

PMID- 20047592
TI  - Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and
      survival of advanced gastric cancer patients treated with cetuximab plus modified
      FOLFOX6.
AB  - Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor
      (EGFR). The present study investigated the association between germline genetic
      polymorphisms and the treatment outcome of cetuximab plus modified leucovovin,
      fluorouracil, and oxaliplatin (FOLFOX)6 chemotherapy in advanced gastric cancer
      (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a
      phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16
      polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth
      factor-alpha (TGFA), thymidylate synthase, excision repair cross-complementation
      group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A
      and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival.
      Twenty-one patients had low repeats (sum of both alleles <or=37), and 17 patients
      had high repeats (sum >or=38). Patients with low CA repeats had longer
      progression-free survival (adjusted hazard ratio [HR] 0.42 [95% confidence
      interval [CI] 0.19-0.96], P = 0.040) and overall survival (adjusted HR 0.40 [95%
      CI 0.16-0.99], P = 0.048) compared with patients with high CA repeats. In
      addition, the tumor EGFR expression was higher in patients with a lower number of
      CA repeats. The association between the CA repeat status and survival was not
      found in a separate cohort of AGC patients (n = 68) treated only with modified
      FOLFOX6. These results suggest that the EGFR intron 1 CA repeat polymorphism
      could be a useful, predictive biomarker of cetuximab efficacy in AGC and merits
      further investigation in randomized studies.

PMID- 20047593
TI  - Myristoylated alanine-rich C kinase substrate phosphorylation promotes
      cholangiocarcinoma cell migration and metastasis via the protein kinase C
      dependent pathway.
AB  - Myristoylated alanine-rich C kinase substrate (MARCKS), a substrate of protein
      kinase C (PKC) has been suggested to be implicated in cell adhesion, secretion,
      and motility through the regulation of the actin cytoskeletal structure. The
      quantitative real-time-polymerase chain reaction analysis revealed that MARCKS is
      significantly overexpressed in Opisthorchis viverrini-associated
      cholangiocarcinoma (CCA) (P = 0.001) in a hamster model, which correlated with
      the results of mRNA in situ hybridization. An immunohistochemical analysis of 60
      CCA patients revealed a significant increase of MARCKS expression. Moreover, the
      log-rank analysis indicated that CCA patients with a high MARCKS expression have
      significantly shorter survival times than those with a low MARCKS expression (P =
      0.02). This study investigated whether MARCKS overexpression is associated with
      CCA metastasis. Using a confocal microscopic analysis of CCA cell lines that had
      been stimulated with the PKC activator, 12-0-tetradecanoyl phorbol-13-acetate
      (TPA), MARCKS was found to be translocated from the plasma membrane to the
      perinuclear area. In addition, phosphorylated MARCKS (pMARCKS) became highly
      concentrated in the perinuclear area. Moreover, an adhesion assay demonstrated
      that the exogenous overexpression of MARCKS remarkably promoted cell attachment.
      Interestingly, after TPA stimulation, the CCA cell line-depleted MARCKS showed a
      decrease in migration and invasion activity. It can be concluded that in non
      stimulation, MARCKS promotes cell attachment to the extracellular matrix. After
      TPA stimulation, PKC phosphorylates MARCKS leading to cell migration or invasion.
      Taken together, the results of this study reveal a prominent role for MARCKS as
      one of the key players in the migration of CCA cells and suggest that cycling
      between MARCKS and pMARCKS can regulate the metastasis of biliary cancer cells.

PMID- 20047594
TI  - Physically active families - de-bunking the myth? A qualitative study of family
      participation in physical activity.
AB  - BACKGROUND: The benefits of physical activity for reducing obesity and related
      chronic diseases are well known. The need for more family-based interventions to
      increase physical activity is frequently cited in the literature; however, little
      is known about if and how families are physically active together, and what
      factors might influence family-based participation in regular physical activity.
      This study examined the types of activities (physical and sedentary) engaged in
      as a family and explored parents' perceptions of the importance, frequency,
      nature and barriers to family physical activity. METHODS: Semi-structured
      telephone interviews were conducted with 30 parents (26 female, four male) of 10-
      to 11-year-old schoolchildren who attended either low, middle or high socio
      economic status schools in Bristol, UK. Interviews were transcribed verbatim,
      anonymized and analysed using conventional content analysis. RESULTS: The
      majority of parents rated family engagement in physical activity as important,
      and identified benefits such as increased parent-child communication, spending
      time together, enjoyment, enhanced mental health, weight control and physical
      fitness. Despite these benefits most parents reported their families did little
      or no physical activity together as a family unit during the week, and any
      activities performed together were usually sedentary in nature. They reported
      increased family physical activity on the weekends but rarely including the full
      family unit simultaneously. Parents in two-parent households commonly paired off
      with one or more children because of complexities of schedules. Commonly reported
      barriers were busy lifestyles, diverse ages and interests of children and adults,
      bad weather, and lack of access to facilities, transportation and money to
      support activities. CONCLUSIONS: Family-based interventions might be more
      effective if they are designed to accommodate the complex demands and needs of
      two-parent and single-parent families and provide affordable, diverse activities
      appealing to a wide range of interests.

PMID- 20047595
TI  - Birth outcomes associated with prenatal participation in a government support
      programme for mothers with low incomes.
AB  - BACKGROUND: Women with low incomes are at higher risk to have low-birthweight
      (LBW) babies and less likely to participate in prenatal support programmes than
      women with higher incomes. This study examined birth outcomes among participants
      in the Newfoundland and Labrador Mother-Baby Nutrition Supplement (MBNS), a
      prenatal programme for women with low incomes that provides a monthly financial
      supplement and printed information on infant health and development, along with a
      referral to public health nursing services. METHODS: Application data (e.g.
      mother's age, education) for those who applied between August 2002 and December
      2004 were obtained from the Provincial Government. Birth outcomes (e.g.
      birthweight, weeks of gestation) were available for 1599 women. Of these, 862
      were parity zero and subsequently delivered full-term infants. Comparisons were
      made on demographics, timeliness of enrolment and rates of full-term LBW.
      RESULTS: Participants were more often single, younger and less educated than the
      average woman who gave birth in the Province or Canada in 2004. Women enrolled
      early were less likely to have a full-term LBW baby than those enrolled late
      (chi(2)((1)) = 4.03, P = 0.045). Mothers enrolled late had a higher rate of full
      term LBW than was the case in the Province [risk ratio (RR) = 2.76, 95%
      confidence interval (CI) = 1.61-4.74] and Canada (RR = 2.53, 95% CI = 1.55-4.21)
      whereas those enrolled earlier, despite increased risk due to low income, age and
      education, single status and zero parity, had rates of full-term LBW on par with
      the Province (RR = 1.29, 95% CI = 0.71-2.32) and Canada (RR = 1.19, 95% CI = 0.68
      2.08). CONCLUSION: The MBNS is an effective intervention for improving birth
      outcomes in women considered at risk. The challenge is to enrol pregnant women as
      early as possible. Future research will examine what programme component or
      combination of components (e.g. financial, information, referral) affects birth
      outcomes.

PMID- 20047596
TI  - Screening injured children for physical abuse or neglect in emergency
      departments: a systematic review.
AB  - BACKGROUND: Screening markers are used in emergency departments (EDs) to identify
      children who should be assessed for possible physical abuse and neglect. We
      conducted three systematic reviews evaluating age, repeat attendance and injury
      type as markers for physical abuse or neglect in injured children attending EDs.
      METHODS: We included studies comparing markers in physically abused or neglected
      children and non-abused injured children attending ED or hospital. We calculated
      likelihood ratios (LRs) for age group, repeat attendance and injury type (head
      injury, bruises, fractures, burns or other). Given the low prevalence of abuse or
      neglect, we considered that an LR of 10 or more would be clinically useful.
      RESULTS: All studies were poor quality. Infancy increased the risk of physical
      abuse or neglect in severely injured or admitted children (LRs 7.7-13.0, 2
      studies) but was not strongly associated in children attending the ED (LR 1.5,
      95% CI: 0.9, 2.8; one study). Repeat attendance did not substantially increase
      the risk of abuse or neglect and may be confounded by chronic disease and socio
      economic status (LRs 0.8-3.9, 3 studies). One study showed no evidence that the
      type of injury substantially increased the risk of physical abuse or neglect in
      severely injured children. CONCLUSIONS: There was no evidence that any of the
      markers (infancy, type of injury, repeated attendance) were sufficiently accurate
      (i.e. LR >or= 10) to screen injured children in the ED to identify those
      requiring paediatric assessment for possible physical abuse or neglect.
      Clinicians should be aware that among injured children at ED a high proportion of
      abused children will present without these characteristics and a high proportion
      of non-abused children will present with them. Information about age, injury type
      and repeat attendances should be interpreted in this context.

PMID- 20047597
TI  - Development of the Child's Challenging Behaviour Scale (CCBS) for mothers of
      school-aged children with disabilities.
AB  - BACKGROUND: Caring for a child with a disability can be especially difficult when
      the child exhibits challenging behaviours. Childhood disability often calls for
      the mother to be conscientious, capable and organized to meet the child's health
      and developmental needs. Mothers are known to feel particularly stressed when
      their child also behaves in ways that are difficult to manage. In these
      circumstances maternal mental health may be compromised and mothers therefore
      need more support. The Child's Challenging Behaviour Scale (CCBS) is an 11-item
      scale that measures a mother's report of challenging behaviours exhibited by
      their child with disability, that are associated with compromised maternal mental
      health and caregiving difficulties. This paper describes the initial development
      and psychometric evaluation of the CCBS. METHODS: A mixed methodology instrument
      design model was used to develop the CCBS. A qualitative study generated items,
      and quantitative data were collected from 152 mothers of a child with a
      disability. RESULTS: The CCBS showed excellent internal consistency (Cronbach's
      alpha = 0.89) and factor analysis supported its unidimensionality. Construct
      validity was supported by correlations with the PedsQL Psychosocial Health
      Summary Score (rho =-0.51) and cooperation taking medication (rho = 0.40). There
      were significant differences in CCBS scores between groups of children with and
      without either autism or psychiatric conditions. The CCBS showed moderate
      correlations with self-reported health status; the mother's sense of empowerment
      (rho =-0.44); and family cohesion (rho =-0.30). Mothers with a mental health
      condition recorded significantly higher CCBS scores. CONCLUSIONS: The CCBS is a
      brief, psychometrically sound instrument that provides clinicians with a new tool
      that measures a mother's rating of their child's behaviours that are challenging
      and associated with reduced maternal well-being. The CCBS assists professionals
      to identify mothers and family situations who may be in need of more support and
      interventions.

PMID- 20047598
TI  - Acceptability and usefulness of the group interaction training programme It Takes
      Two to Talk to parents of pre-school children with motor disorders.

PMID- 20047599
TI  - Prevalence and social patterning of limiting long-term illness/disability in
      children and young people under the age of 20 years in 2001: UK census-based
      cross-sectional study.

PMID- 20047600
TI  - Parenting stress in US families: implications for paediatric healthcare
      utilization.
AB  - OBJECTIVE: According to family stress models, parental responses to stress
      disrupt interactions between parent and child and may lead to parental inability
      to seek timely medical care for their child. The objective of this study was to
      quantitatively assess the relationship between high parenting stress and child
      healthcare utilization. METHODS: We used the 2003-2004 National Survey of
      Children's Health to determine the prevalence of parenting stress in US families
      and associated socio-demographic variables. We used weighted logistic regression
      to investigate associations between parenting stress and healthcare utilization,
      controlling for other parental psychosocial and socio-demographic variables. The
      primary independent variables were parenting stress, parental mental health,
      parental coping and social support. The main dependent variables were emergency
      care, sick visits to primary care and preventive care in the past 12 months.
      RESULTS: Nationally, 13% of children lived in households with at least one parent
      experiencing high parenting stress. Socio-demographic variables associated with
      the highest odds of parenting stress included Black race, special needs status
      and non-English primary language. Parents with high parenting stress had a higher
      odds (adjusted odds ratio 1.24, 95% confidence interval 1.10-1.41) of seeking
      emergency care for their children compared with parents with low parenting
      stress, controlling for other parental psychosocial factors and socio-demographic
      variables. CONCLUSIONS: Having a parent who is experiencing high parenting stress
      is associated with greater utilization of paediatric emergency care.
      Interventions targeted at parenting stress may provide families with needed
      support and reduce unnecessary emergency care utilization.

PMID- 20047601
TI  - Adverse birth outcomes among pregnancies of teen mothers: age-specific analysis
      of national data in Taiwan.
AB  - BACKGROUND: This study was conducted to evaluate the risks of adverse birth
      outcomes including low birthweight, preterm and small-for-gestational age among
      teen mothers. METHODS: Data were collected from the Taiwan Birth Registry between
      1985 and 1997. Among a total of 1,185,597 live births born to mothers aged 24
      years or less, 151,259 (12.8%) were born to teen mothers aged 19 years or less.
      Crude odds ratios (ORs), adjusted ORs (AORs), their 95% confidence intervals and
      test for linear trend of maternal age-specific AOR were estimated using logistic
      regression analysis. RESULTS: After controlling for certain birth characteristics
      and socio-economic factors, the age-specific analysis showed significantly
      gradient variations in increased risks of adverse birth outcomes among births of
      teen mothers, where the elevated risk was lessened in older teen mothers. Teen
      mothers aged 16 years or less were observed to experience particularly high AORs
      for all adverse birth outcomes of interest. CONCLUSIONS: Not all teen mothers
      experienced the same magnitude of increased risk of adverse birth outcomes in
      Taiwan. Considering all teen mothers as the same group may have overlooked the
      particularly high risks of adverse birth outcomes among very young teen mothers
      (16 years or less), who are especially vulnerable to such elevated risks.

PMID- 20047602
TI  - Utility of the rapid antigen detection BinaxNOW Influenza A&B test for detection
      of novel influenza A (H1N1) virus.
AB  - Nasopharyngeal aspirates, collected during outbreaks, of the novel influenza A
      (H1N1) virus in Barcelona, were used to compare the accuracy of a rapid antigen
      based test (Binax) with the real-time RT-PCR assay developed by the CDC. The
      sensitivity, specificity and positive predictive value of the rapid test are
      higher in patients less than 18 years old and during the acute stage of the
      epidemic than in adult patients.

PMID- 20047607
TI  - In-vitro activities of tetracyclines, macrolides, fluoroquinolones and
      clindamycin against Mycoplasma hominis and Ureaplasma ssp. isolated in Germany
      over 20 years.
AB  - Antimicrobial resistance in genital mycoplasmas is increasing and shows global
      variation. We determined the susceptibilities of 469 mycoplamas, comprising 290
      Mycoplasma hominis and 179 ureaplasma isolates collected during 1983 and 1989
      2004, to eleven antibacterials by agar dilution. Additionally, we analyzed the
      results of routine E-testing during 2005-2008. Doxycycline was the most active
      tetracycline with (MIC90 of 1 and 8 mg/L for ureaplasmas and M. hominis,
      respectively. Significantly more M. hominis isolates (approximately 10-13%) than
      ureaplasmas (approximately 1-3%) were resistant to tetracyclines. Ofloxacin was
      effective against both species (>95% susceptibility). Ciprofloxacin was
      moderately active against M. hominis and less active against ureaplasmas (70.3%
      and 35.2% susceptibility, respectively). Clarithromycin and josamycin were the
      most potent macrolides (MIC90 of 0.5 mg/L) against ureaplasmas. Erythromycin had
      the lowest activity (MIC90 of 8 mg/L) against ureaplasmas like clindamycin which
      was the most potent agent against M. hominis. Cross-resistance was found between
      tetracyclines (53-93%), macrolides and erythromycin (70-100%), and between
      erythromycin and ciprofloxacin (43-55%). M. hominis became more resistant to
      tetracyclines and fluoroquinolones between 1989 and 2004, although there was
      little change during 2005-2008. Ureaplasmas became more resistant to cipfloxacin
      during 1997 - 2004 and showed high resistance rates to erythromycin during 1989
      2008. Doxycycline is still the drug of first-choice for the treatment of
      ureaplasmal infections and may be used for co-infection with M. hominis.

PMID- 20047608
TI  - Transplantation with pancreas after living donor kidney vs. living donor kidney
      alone in type 1 diabetes mellitus recipients.
AB  - Living donor kidney transplantation (LDKT) in type 1 diabetic recipients (T1DM)
      may be followed by a pancreas after living donor kidney (PALK). The impact of the
      PALK is largely unknown. Adult T1DM living donor kidney recipients (1997-2007)
      listed for pancreas transplantation were divided into those who subsequently
      received pancreas transplantation and those who did not (living donor kidney
      transplant alone [LDKA]). Outcomes were compared. A sub-analysis was performed in
      recipients with at least one yr of kidney graft survival and limiting PALK to
      those who underwent pancreas transplantation in the first year. Of 4554
      recipients, 23% received PALK. PALK had more favorable baseline characteristics.
      At the end of eight yr, we found significantly superior patient (85% vs. 75%) and
      kidney graft survival (75% vs. 62%) in PALK group. The adjusted hazard ratios of
      PALK (LDKA as reference) were 0.65 (95%CI: 0.52-0.81) for death and 0.63 (0.54
      0.76) for renal graft loss. In sub-group analysis, there was a trend toward
      decreased death in PALK (HR = 0.78: 0.57-1.07). In conclusion, only 23% of those
      wait-listed received a pancreas with patient and kidney survival superior to
      LDKA. Pancreas transplant in the first year after kidney transplant was
      associated with a trend toward better long-term patient survival.

PMID- 20047609
TI  - Metabolic syndrome and new onset diabetes after transplantation in kidney
      transplant recipients.
AB  - BACKGROUND: Metabolic syndrome (MS) and new onset diabetes after transplant
      (NODAT) are common in kidney transplant patients. We studied the relationship
      between the two conditions and their impact on metabolic and cardiovascular risk
      profiles. METHODS: All non-diabetic patients transplanted between 1999 and 2005
      who were followed up to 2006 were included. MS and NODAT were determined. Kaplan
      Meier survival and various regression analyses were performed to determine the
      clinical correlates for both conditions and their association with various
      cardiovascular risk factors. RESULTS: Among 591 patients, 314 (53.1%) had MS and
      90 (15.2%) developed NODAT. The two conditions were highly associated with each
      other as 84 patients with NODAT also had MS (14.2%). Elevated body mass index and
      fasting glucose levels at transplant were risk factors for both conditions,
      whereas weight gain after transplant was associated only with MS. African
      American, old age, and hypertension-related ESRD were risk factors for NODAT.
      Finally, the presence of MS was associated with reduced kidney function and
      elevated uric acid levels, whereas the presence of NODAT with elevated pulse
      pressure. CONCLUSIONS: MS and NODAT are highly prevalent and significantly
      associated with impaired metabolic and cardiovascular risk profiles. Early
      identification of such conditions may facilitate targeted therapeutic
      intervention.

PMID- 20047610
TI  - Randomized trial of early corticosteroid reduction vs. regular-dose
      corticosteroid maintenance in combination with tacrolimus and mycophenolate
      mofetil in living donor kidney transplant recipients: the Brazilian CORRETA
      trial.
AB  - This multicenter, randomized trial aimed to compare the safety and efficacy of an
      early reduction in corticosteroid dose vs. long-term maintenance in Brazilian
      patients on an immunosuppressive regimen based on tacrolimus and mycophenolate
      mofetil (MMF). In the control arm, prednisone was progressively reduced from days
      8 to 90 and then kept for 12 months. In the experimental arm, prednisone was
      given for 12 months at the dose of 5 mg every other day. Endpoints were the
      composite occurrence of death, graft loss, or Banff III acute rejection, and
      safety. A total of 83 patients were enrolled, and 77 were analyzed for efficacy
      safety. One death occurred in each group. There were no cases of graft loss and
      one case of grade 3 acute rejection in the early reduction arm. There was no
      difference in the rate of the composite primary endpoint between both arms
      (p=0.215), and there were no significant differences between both arms in terms
      of adverse events. Except for higher incidence of hypertriglyceridemia levels
      among patients in the regular-dose arm, there were no significant differences
      between both arms in terms of adverse events. The results of this trial suggest
      that early reduction of corticosteroid can be feasible and safe within a
      timeframe of 12 months in patients receiving tacrolimus and MMF.

PMID- 20047611
TI  - Risk factors for pneumonia caused by multidrug-resistant Gram-negative bacilli
      among liver recipients.
AB  - Pneumonia caused by multidrug-resistant (MDR) Gram-negative bacilli is associated
      with a higher mortality rate. The appropriate empiric therapy is based on the
      understanding of local etiology and MDR pattern. This study was to evaluate the
      spectrum of Gram-negative bacilli, MDR rate, risk factors and mortality in 475
      liver transplantation (LT) recipients. In the first six months after LT, the
      incidence of bacterial pneumonia was 21.3% (101/475). The overall infectious
      incidence during the first post-transplant month was 80.2%. The most frequent
      pneumonia isolates were Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas
      aeruginosa and Staphylococcus aureus. Gram-negative bacilli accounted for 69.6%
      of all pneumonia pathogens. Of the main 124 Gram-negative bacilli isolates, MDR
      rate was 58.9%. Four risk factors for post-LT pneumonia caused by MDR Gram
      negative bacilli were LT candidates with grade II-IV encephalopathy (OR 2.275,
      95%CI 1.249-4.124, p = 0.006), prolonged duration of endotracheal intubation (OR
      8.224, 95%CI 4.276-15.815, p = 0.013), tracheostomy (OR 4.929, 95%CI 1.099
      18.308, p = 0.027) and post-LT episode(s) of reoperations (OR 10.597, 95%CI 3.726
      30.134, p < 0.001). MDR Gram-negative bacterial pneumonia-related mortality was
      significantly higher than that because of antibiotic-susceptible bacilli (45.6%
      vs. 11.4%, p = 0.010). Our data suggest that pneumonia caused by MDR Gram
      negative bacilli after LT is common, and associated with the severity of
      underlying disease, prolonged mechanical ventilation and upper abdominal surgery.

PMID- 20047612
TI  - Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six
      months following renal transplant.
AB  - BACKGROUND: Specific anti-human leukocyte antigen antibodies (HLA) in the post
      transplant period may be present with acute rejection episodes (ARE), and high
      soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss.
      METHODS: HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels
      were determined prior to transplantation in 72 patients. Soluble CD30 levels and
      PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.
      RESULTS:   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine
      of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive
      PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had
      donor-specific antibodies (DSA) in serum samples pre-transplantation, two
      subjects developed DSA. Three subjects without ARE had positive PRA only in post
      transplantation samples. Soluble CD30 levels were higher in pre-transplant
      samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30
      levels were elevated in subjects who experienced rejection and were significantly
      higher at seven d (p = 0.0004) and six months (p = 0.03). CONCLUSIONS: Higher
      sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels
      may represent a risk factor for acute rejection.

PMID- 20047613
TI  - Significance of patient self-monitoring for long-term outcomes after lung
      transplantation.
AB  - BACKGROUND: Lung transplant (LTx) recipients' adherence to regular self
      monitoring of lung function (SMLF) is important in maintaining health. This study
      investigated patients' behavior based on electronic monitoring (EM) and compared
      these findings with self-reported data. METHODS: This single-center study
      included 269 patients following LTx. Patients reported on adherence regarding
      SMLF, and data were compared to electronically stored measurements for the last
      three months prior to self-reporting. RESULTS: Non-adherence was 59.4% based on
      EM for a total of 22,052 measurements performed. Main reported reasons for non
      adherence were forgetfulness (22%), lack of time (19%), and good self-perception
      of health status (19%). Determinants for non-adherence were patients constraining
      beliefs (p <= 0.0001), low perceived support from the transplant center (p <=
      0.008), a history of infections (p <= 0.014) and rejections (p <= 0.043), and
      bronchiolitis obliterans (p <= 0.006). Multiple logistic regression revealed low
      perceived support from the transplant center (OR 3.22; 95% CI 1.32-7.83; p <
      0.01), and lack of support from patient organizations (OR 2.19; 95% CI 1.02-4.72;
      p < 0.04) as independent predictors for non-adherence. CONCLUSIONS: LTx
      recipients had some difficulties maintaining SMLF on a daily basis. Non-adherence
      regarding lung function monitoring may provide a clinically relevant estimate of
      suspect cases for critical events impacting outcomes after LTx.

PMID- 20047614
TI  - Bone marrow cells obtained from cirrhotic rats do not improve function or reduce
      fibrosis in a chronic liver disease model.
AB  - BACKGROUND: The objective of this study was to evaluate the therapeutic potential
      of bone marrow cells (BMCs) obtained from cirrhotic donors in a model of chronic
      liver disease. METHODS: Chronic liver injury was induced in female Wistar rats by
      the association of an alcoholic diet with intraperitoneal injections of carbon
      tetrachloride. BMCs obtained from cirrhotic donors or placebo were injected
      through the portal vein. Blood analysis of alanine aminotransferase (ALT) and
      albumin levels, ultrasound assessment including the measurement of the portal
      vein diameter (PVD) and liver echogenicity, histologic evaluation with
      hematoxylin and eosin and Sirius red staining, and quantification of collagen
      deposition were performed. RESULTS: ALT and albumin blood levels showed no
      significant differences between the experimental groups two months after
      injection. Additionally, no significant variation in PVD and liver echogenicity
      was found. Histological analysis also showed no significant variation in collagen
      deposition two months after placebo or BMC injection. CONCLUSION: This study
      suggests that, even though BMC therapy using cells from healthy donors has
      previously shown to be effective, this is not the case when BMCs are obtained
      from cirrhotic animals. This result has major clinical implications when
      considering the use of autologous BMCs from patients with chronic liver diseases.

PMID- 20047615
TI  - Comparison of biliary complications in adult living-donor liver transplants
      performed at two busy transplant centers.
AB  - Adult living-donor liver transplantation (ALDLT) has a high rate of biliary
      complications. We identified risk factors that correlate with biliary leaks and
      strictures by combining data from two centers. Records of ALDLT right lobe
      recipients (n = 156) at two centers between December 1998 and February 2005 were
      reviewed. Leak rate was analyzed in 144 recipients after we excluded those with
      hepatic artery thrombosis or death within 30 d of transplant. Stricture rate was
      also analyzed in 132 recipients after we excluded those with graft survival or
      follow-up <180 d. Biliary reconstructions were performed using either duct-to
      duct (DD) or Roux-en-Y hepaticojejunostomy and were subclassified by anatomic
      type, number of anastomoses performed, and stent use. Prevalence of a leak and/or
      a stricture was 39%; 11% of recipients developed both. Single DD anastomoses
      between the graft right hepatic duct to the recipient common duct had
      significantly lower incidence of leaks compared to all other anastomotic types.
      Early leak was predictive of late stricture development (p = 0.006), but
      recipient demographics, diagnosis, warm ischemia time, anastomosis type, duct
      number, year of transplant, stent use, and transplant center were not. The
      results suggest donors with a single right hepatic duct reconstructed to the
      recipient common bile duct are the most likely to avoid biliary problems after
      ALDLT.

PMID- 20047616
TI  - Transition from donor candidates to live kidney donors: the impact of race and
      undiagnosed medical disease states.
AB  - BACKGROUND: Living kidney donors (LKD) allow for increased access to lifesaving
      organs for transplantation. There is a relative paucity of African American (AA)
      live kidney donors. The prevalence of medical disease in LKD candidates has not
      been well studied. We examined the medical limitations to living kidney donation
      in a large Midwestern transplant center. METHODS: A total of 2519 adults (age >=
      18) evaluated as potential LKD (PD) between January 1, 1996 and June 30, 2006
      were prospectively followed until evaluation outcome (completed live donation,
      medical exclusion from live donation, non-medical exclusion from live donation).
      Logistic regression was used to examine the effect of age on donor exclusion, and
      chi-square tests were used to compare the likelihood of donor exclusions between
      racial and gender groups. RESULTS: Sixty percent of PD were female (n = 1300),
      and 86% were Caucasian (CA) (n = 1862). Overall, 48.7% of PD who underwent
      evaluation became LKD. The odds of donation were 52% lower in AA compared to CA
      (OR 0.48 p < 0.001). Among PD excluded from donation, the most common medical
      diagnoses were hypertension (HTN) (24.7%), inadequate creatinine clearance
      (10.6%) and a positive final crossmatch (10.5%). The rate of PD exclusion for
      obesity was twofold higher in AA compared to CA (12.8% vs. 5.8%, p < 0.001).
      CONCLUSIONS: Hypertension in PD is equally significant barrier to living kidney
      donation in AA and CA whereas obesity is a greater barrier in AA.

PMID- 20047617
TI  - The association between eNOS intron 4 VNTR polymorphism and delayed graft
      function of kidney allografts.
AB  - Nitric oxide (NO) is a multifunctional agent which serves as a key signaling
      molecule in physiological processes such as host defense, neuronal communication,
      and the regulation of vascular tone. Different polymorphic variations have been
      identified in the human NOS3 (eNOS) gene.The aim of the present study was to
      examine the association between polymorphisms of the NOS3 gene (G894T
      substitution within exon 7 and intron 4 VNTR polymorphism) and the development of
      delayed graft function as well as acute and chronic rejection.One hundred eighty
      seven recipients of first renal transplants were included in the study. There
      were no significant associations between these polymorphisms and acute and
      chronic kidney allograft rejection. The intron 4 polymorphism was associated with
      delayed graft function after transplantation. The results of this study suggest
      that patients with the a allele of the eNOS intron 4 VNTR polymorphism may be
      predisposed to delayed graft function.

PMID- 20047618
TI  - Randomized crossover study to assess the inter- and intrasubject variability of
      morning mycophenolic acid concentrations from enteric-coated mycophenolate sodium
      and mycophenolate mofetil in stable renal transplant recipients.
AB  - The delayed release of mycophenolic acid (MPA) from enteric-coated mycophenolate
      sodium (EC-MPS, myfortic(r)) may have an impact on the variability of MPA trough
      (C0 h) levels. A randomized, two-period crossover study was performed in 24
      maintenance renal transplants to evaluate the inter- and intrasubject variability
      of MPA predose levels from EC-MPS and mycophenolate mofetil (MMF, CellCept(r)),
      both in combination with cyclosporine. Patients received EC-MPS (720 mg b.i.d.)
      and MMF (1000 mg b.i.d.) for a period of 21 d each. MPA plasma levels were
      measured over the final seven consecutive days at -1, 0, 1, 2, and 3 h after the
      morning MPA dose. Intersubject coefficients of variation (%CV) for MPA troughs
      were 47.5% (95% CI, 34.1-80.3) and 54.4% (40.0-86.8) for EC-MPS and MMF,
      respectively; intrasubject %CVs were 62.7% (55.1-72.9) and 42.8% (37.9-49.2).
      High MPA C0 h levels>10 MUg/mL were rarely observed with both EC-MPS (1.8%) and
      MMF (0.6%). Mean MPA area under the curve (AUC)0-3 h was comparable between
      treatments, while MPA C0 h was on average 46% higher with EC-MPS. In conclusion,
      predose MPA trough level monitoring appears of limited value during EC-MPS and
      MMF therapy given the large intrasubject variability in MPA C0 h levels with both
      treatments.

PMID- 20047619
TI  - Measurement of CD4+ T-cell function in predicting allograft rejection and
      recurrent hepatitis C after liver transplantation.
AB  - Recurrence of hepatitis C virus (HCV) can be difficult to distinguish from acute
      cellular rejection (ACR) following liver transplantation. The Cylex Immune
      Function Assay (ImmuKnow) provides objective measure of recipient's immune
      function. The goal is to assess the ability of this assay to distinguish these
      similar conditions. A retrospective review was performed in 54 recipients with
      HCV. ImmuKnow assays were measured with allograft biopsies. Levels of adenosine
      triphosphate (ATP) release from CD4+ T cells (ng/mL) were compared with the
      following biopsy result classifications: 365 +/- 130 with ACR (n = 11), 152 +/-
      100 with recurrent HCV (n = 26), 240 +/- 71 with normal biopsies (n = 12), and
      157 +/- 130 with overlapping features of ACR and recurrent HCV (n = 5).
      Recipients with recurrent HCV had lower immune response than those with ACR (p <
      0.0001).Using a cutoff level of 220, the sensitivity and specificity for
      distinguishing two conditions were 88.5% and 90.9%, respectively. When recipients
      with overlapping features had low immune response, three of four recipients'
      subsequent biopsies showed recurrent HCV. In conclusion, the ImmuKnow assay can
      be a sensitive and specific additional test for distinguishing recurrent HCV from
      ACR and may be useful for predicting which recipients may be most vulnerable to
      recurrent HCV.

PMID- 20047620
TI  - Colestilan monotherapy significantly improves glycaemic control and LDL
      cholesterol levels in patients with type 2 diabetes: a randomized double-blind
      placebo-controlled study.
AB  - AIM: To evaluate the plasma glucose-reducing activity and safety of colestilan, a
      bile acid sequestrant, in patients with type 2 diabetes. METHODS: Patients with
      fasting plasma glucose (FPG) 7.2-11.1 mmol/l and HbA (1c)> or =7.0% were randomly
      allocated in double-blind manner to receive colestilan or placebo therapy for 12
      weeks. RESULTS: A total of 183 patients entered the double-blind treatment phase.
      At 12 weeks, colestilan significantly reduced HbA (1c) and FPG vs. placebo by
      0.9% and 1.2 mmol/l respectively (both p < 0.001). A significant (p < 0.001)
      22.5% reduction of LDL cholesterol was also observed in the 172 patients
      evaluated (colestilan group: n = 86; placebo group: n = 86). However, no
      significant reduction of fasting insulin was observed (p = 0.087). No incidence
      of hypoglycaemia was reported in this study. CONCLUSION: Colestilan improved
      glycaemic control and reduced LDL cholesterol levels in patients with type 2
      diabetes.

PMID- 20047621
TI  - Misleading results of randomized trials: the example of renal artery stenting.

PMID- 20047622
TI  - Efficacy of an olmesartan medoxomil-based treatment algorithm in patients
      stratified by age, race, or sex.
AB  - Demographic factors are known to influence the prevalence of hypertension, and
      evidence suggests that they may also influence the response of patients with
      hypertension to blood pressure (BP)-lowering therapies. To determine the effect
      of demographic factors on the efficacy and safety of an olmesartan medoxomil (OM)
      based treatment regimen, we performed a prespecified subgroup analysis of a 12
      week, randomized, placebo-controlled, titrate-to-goal study in patients with
      hypertension, stratifying patients into treatment groups according to age, sex,
      or race. After 12 weeks, OM-based therapy significantly reduced BP from baseline
      in blacks, non-blacks, men, women, and patients younger than 65 or 65 years and
      older compared with placebo, and enabled 51.9% to 79.5% of patients to achieve a
      BP goal of <140/90 mm Hg. The differences in BP-lowering efficacy of OM-based
      therapy between subgroups were not clinically significant, and treatment was
      generally well tolerated in all groups. This study demonstrates that an OM-based
      treatment algorithm is an effective and safe option for achieving recommended BP
      goal in patients with hypertension including blacks, non-blacks, men, women, and
      patients younger than 65 or 65 years and older.

PMID- 20047624
TI  - Comparison of office, ambulatory, and home blood pressure antihypertensive
      response to atenolol and hydrochlorthiazide.
AB  - Office, home, and ambulatory blood pressure (BP) demonstrate variable
      associations with outcomes. The authors sought to compare office BP (OBP), home
      BP (HBP), and ambulatory BP (ABP) for measuring responses to hydrochlorothiazide
      (HCTZ), atenolol, and their combination. After completing washout, eligible
      patients were randomized to atenolol 50 mg or HCTZ 12.5 mg daily. Doses were
      doubled after 3 weeks and the alternate drug was added after 6 weeks if BP was
      >120/70 mm Hg (chosen to allow maximum opportunity to assess genetic associations
      with dual BP therapy in the parent study). OBP (in triplicate), HBP (twice daily
      for 5 days), and 24-hour ABP were measured at baseline, after monotherapy, and
      after combination therapy. BP responses were compared between OBP, HBP, and ABP
      for each monotherapy and combination therapy. In 418 patients, OBP overestimated
      BP response compared with HBP, with an average 4.6 mm Hg greater reduction in
      systolic BP (P<.0001) and 2.1 mm Hg greater reduction in diastolic BP (P<.0001)
      across all therapies. Results were similar for atenolol and HCTZ monotherapy. ABP
      response was more highly correlated with HBP response (r=0.58) than with OBP
      response (r=0.47; P=.04). In the context of a randomized clinical trial, the
      authors have identified significant differences in HBP, OBP, and ABP methods of
      measuring BP response to atenolol and HCTZ monotherapy.

PMID- 20047626
TI  - Assessing the validity of the Omron HEM-907XL oscillometric blood pressure
      measurement device in a National Survey environment.
AB  - Blood pressure (BP) readings taken by Omron HEM-907XL were compared with the
      results obtained using sphygmomanometer (HgS) in 509 individuals using 2002
      Association for the Advancement of Medical Instrumentation (AAMI) criteria. With
      the exception of diastolic BP in youth ages 13 to 19 years (mean difference, 
      1.77 mm Hg; standard deviation, 8.65), the Omron device met the criteria.
      Agreement for hypertension (BP >or=140/90 mm Hg) was above chance (kappa=0.68)
      and, compared with HgS, Omron underestimated the prevalence of hypertension by
      2.65%. The Omron and HgS measurements were highly correlated (r=0.94 for systolic
      BP and r=0.83 for diastolic BP). Both increased systolic and diastolic BP
      decreased device agreement (beta-coefficient=-0.10872, P<.0001; beta-coefficient=
      0.25981, P<.0001, respectively). The Omron device meets AAMI criteria with the
      exception of diastolic BP in youth ages 13 to 19 years. However, Omron
      underestimated the prevalence of hypertension and device agreement decreases with
      increased systolic and diastolic BP.

PMID- 20047627
TI  - Treatment of hypertension in the inpatient setting: use of intravenous labetalol
      and hydralazine.
AB  - Acute blood pressure elevations are commonly treated in hospitalized patients.
      There are no guidelines for appropriate practice and no evidence that such
      treatment is useful. The authors performed a retrospective review of medical and
      pharmacy records to determine how often intravenous hydralazine and labetalol are
      ordered and administered. During a 1-year study period, a total of 29,545
      hospitalizations were recorded. The authors identified 2189 patients (7.4% of all
      patients) for whom 7242 orders were written for hydralazine as needed (10-20 mg
      per dose) and 5915 for labetalol (10-20 mg per dose). Ordered drugs were
      administered in 60.3% of patients, and the average number of doses administered
      was 5.3+/-8.2 (mean +/- SD) for hydralazine and 5.6+/-7.7 for labetalol. Hospital
      length of stay (LOS) for patients for whom hydralazine was ordered was 12.0+/
      15.9 days for those who received at least 1 dose and 7.1+/-9.0 days for those who
      did not receive a dose (P<.001). For patients for whom labetalol was ordered,
      patients receiving at least 1 dose had an LOS of 11.8+/-16.1 days vs 7.9+/-10.4
      days for those who did not receive a dose (P<.001). Treatment of elevated blood
      pressure in in-patients is a common practice. The authors suggest that evidence
      is needed to determine whether the practice is of benefit.

PMID- 20047628
TI  - Secondary hypertension in overweight and stage 1 hypertensive children: a Midwest
      Pediatric Nephrology Consortium report.
AB  - According to the Fourth Report on the Diagnosis, Evaluation, and Treatment of
      High Blood Pressure in Children and Adolescents, stage 1 hypertension is often
      primary in origin and associated with overweight. In contrast, stage 2
      hypertension is more often secondary in origin and, hence, requires more
      extensive evaluation according to task force recommendations. The objective of
      this retrospective study was to evaluate whether the presence of stage 1
      hypertension in overweight pediatric patients precludes workup for secondary
      hypertension (SH). This study included children (5-18 years) with hypertension
      (defined and staged per task force recommendations) referred to 4 pediatric
      nephrology centers in the Midwest region. Of the 246 referred patients, 166
      patients with primary hypertension (PH) and SH were included for body mass index
      and hypertension stage analysis. The study revealed no significant differences in
      the mean age at diagnosis (PH, 13.1+/-3.1 years; SH, 12.4+/-3.8 years),
      distribution of overweight (PH, 89.4% BMI >85th percentile; SH, 80% BMI >85th
      percentile), and stage 1 (PH, 45%; SH, 40%) or 2 hypertensive (PH,55%; SH, 60%)
      children between PH vs SH. Overweight and presence of stage 1 hypertension should
      not preclude evaluation for SH.

PMID- 20047629
TI  - Compliance with the treatment of hypertension: the potential of combination
      therapy.
AB  - Patient adherence to antihypertensive medication is vital to ensure the
      successful treatment of hypertension. Low levels of adherence to and persistence
      with prescribed therapy are major factors leading to the current poor rates of
      blood pressure control among patients with hypertension. There are many reasons
      for nonadherence to therapy including patient-, physician-, and therapy-related
      factors. Poor tolerability has a detrimental effect on adherence, therefore
      reducing the apparent effectiveness of agents with dose-dependent side effects.
      Various effective combination therapies are recommended by current guidelines,
      eg, beta-blocker plus calcium channel blocker (CCB), angiotensin receptor blocker
      (ARB) plus thiazide diuretic, angiotensin-converting enzyme (ACE) inhibitor plus
      thiazide diuretic, CCB plus thiazide diuretic, ACE inhibitor plus CCB, and ARB
      plus CCB, and these have the potential to increase adherence to therapy by
      combining a favorable tolerability profile with once-daily dosing.

PMID- 20047632
TI  - Dysglycemia predicts cardiovascular and kidney disease in the Kidney Early
      Evaluation Program.
AB  - The cardiometabolic syndrome has been associated with both chronic kidney disease
      (CKD) and cardiovascular disease (CVD). Using data from the National Kidney
      Foundation-Kidney Early Evaluation Program, the authors sought to investigate
      this association in a targeted CKD cohort. A total of 26,992 patients met
      eligibility criteria including age 18 years and older, diabetes, hypertension, or
      family history of CKD, diabetes, or hypertension and excluded those taking renal
      replacement therapy. Individuals were identified by Third Report of the National
      Cholesterol Education Program Adult Treatment Panel (NCEP-ATP III) criteria
      (dysglycemia, hypertension, and dyslipidemia) and World Health Organization
      criteria (obesity and proteinuria). Univariate and multivariate analyses were
      used to evaluate increasing components of the cardiometabolic syndrome, CKD, and
      CVD. On multivariate analysis there was a graded relationship between increasing
      components with an increased prevalence of CKD and CVD. Additionally, there was a
      graded trend with the stage of dysglycemia (eg, normoglycemia, prediabetes, and
      overt diabetes) and increasing CKD. However, there was only an increased
      prevalence of CVD observed in the clinically diabetic group. This trend was also
      observed with increasing serum glucose levels and an increasing percent of CVD
      and CKD up to 160 mg/dL. However, prevalent CVD increased at >140 mg/dL and
      prevalent CKD at >180 mg/dL. Therefore, data support that increasing metabolic
      components and dysglycemia are strongly associated with an increased prevalence
      of CKD and CVD.

PMID- 20047633
TI  - Obesity-related cardiorenal syndrome.
AB  - The term obesity cardiomyopathy has previously been used to describe a clinical
      syndrome in obese patients typically consisting of eccentric left ventricular
      hypertrophy with preserved ejection fraction and diastolic dysfunction and is
      often associated with right ventricular dysfunction independent of the presence
      of the obstructive sleep apnea syndrome. Although several publications have
      described the early stages of this syndrome, little is known about the end stages
      of the disease. The authors conducted a retrospective study of a subset of
      edematous obese patients with multiple common medical comorbidities who present
      with a clinical syndrome in the setting of physiologic stress or infection. Under
      severe physiologic stress these patients developed pulmonary hypertension, right
      sided volume overload, decreased effective arterial blood volume, and renal
      failure. Often, these findings were in the setting of obstructive sleep apnea.
      This retrospective study focuses on an obesity-related cardiorenal syndrome but
      also serves to provide a foreground for acknowledging the broad spectrum of
      cardiovascular pathology, including pulmonary hypertension, diastolic
      dysfunction, and sleep apnea, seen in the obese.

PMID- 20047634
TI  - The effects of resistance training on metabolic health with weight regain.
AB  - To determine whether resistance training effectively maintains improvements in
      cardiometabolic syndrome risk factors during weight regain, 9 individuals lost 4%
      to 6% of their body weight during an 8- to 12-week diet- and aerobic exercise
      induced weight loss phase followed by a controlled weight regain phase (8-12
      weeks), during which they regained approximately 50% of the lost weight while
      participating in a supervised resistance training program. Following weight loss
      (6.0%+/-0.3%), body mass index, body fat percentage, waist circumference, all
      abdominal adipose tissue depots, total cholesterol, low-density lipoprotein
      cholesterol, insulin, and homeostasis model assessment (HOMA) were significantly
      reduced, while quantitative insulin-sensitivity check index (QUICKI) and
      cardiorespiratory fitness (maximal oxygen consumption) significantly increased.
      During weight regain (48.3%+/-3.3% of lost weight), body fat percentage, waist
      circumference, and maximal oxygen consumption were maintained and muscular
      strength and lean body mass significantly increased. Abdominal adipose tissue
      depots, insulin, HOMA, and QUICKI did not significantly change after weight
      regain. Resistance training was effective in maintaining improvements in
      metabolic health during weight regain.

PMID- 20047636
TI  - Impaired intestinal gas propulsion in manometrically proven dysmotility and in
      irritable bowel syndrome.
AB  - BACKGROUND: Intestinal manometry is the current gold standard for diagnosing
      small bowel dysmotility; however, the functional significance of abnormal
      manometry is unknown. Our aim was to determine whether, and to what extent,
      intestinal gas propulsion is impaired in patients with manometrically proven
      dysmotility compared with healthy controls and patients with IBS. METHODS:
      Clearance and tolerance of a jejunal gas load (12 mL min(-1) for 2 h) were
      measured in 15 patients with severe abdominal symptoms and intestinal dysmotility
      evidenced by manometry, 15 patients with IBS and 15 healthy subjects. Thereafter,
      the effect of neostigmine (0.5 mg i.v. bolus) vs placebo (i.v. saline) was tested
      in six dysmotility patients. KEY RESULTS: After 2-h gas infusion, patients with
      dysmotility developed significantly more gas retention (717 +/- 91 mL) than IBS
      patients (372 +/- 82 mL; P = 0.0037) and healthy subjects (17 +/- 67 mL; P <
      0.0001 vs dysmotility; P = 0.0060 vs IBS). Despite the greater retention in
      dysmotility patients, abdominal perception (2.5 +/- 0.6 score) and distension (7
      +/- 2 mm girth increment) were similar to IBS (3.9 +/- 0.6 score and 7 +/- 2 mm,
      respectively). In dysmotility patients, neostigmine produced immediate clearance
      of gas, and by 30 min had reduced gas retention (by -552 +/- 182 vs 72 +/- 58 mL
      after saline; P = 0.008), abdominal symptoms (by -0.8 +/- 0.3 score vs 0.3 +/-
      0.2 after saline; P = 0.019) and distension (girth change -5 +/- 1 mm; P = 0.003
      vs-2 +/- 2 mm after saline). CONCLUSION & INFERENCES: Patients with manometric
      dysmotility have markedly impaired intestinal gas propulsion. In IBS patients,
      impaired gas propulsion is less pronounced but associated with concomitant
      sensory dysfunction and poor tolerance of gas retention.

PMID- 20047637
TI  - The contractile deceleration point: an important physiologic landmark on
      oesophageal pressure topography.
AB  - BACKGROUND: This study aimed to correlate oesophageal bolus transit with features
      of oesophageal pressure topography (OPT) plots and establish OPT metrics for
      accurately measuring peristaltic velocity. METHODS: About 18 subjects underwent
      concurrent OPT and fluoroscopy studies. The deglutitive Contractile Front
      Velocity (CFV) in OPT plots was subdivided into an initial fast phase (CFV(fast))
      and subsequent slow phase (CFV(slow)) separated by a user-defined deceleration
      point (CDP). Fluoroscopy studies were analyzed for the transition from the
      initial rapidly propagated luminal closure associated with peristalsis to slow
      bolus clearance characteristic of phrenic ampullary emptying and to identify the
      pressure sensors at the closure front and at the hiatus. Oesophageal pressure
      topography measures were correlated with fluoroscopic milestones of bolus
      transit. Oesophageal pressure topography studies from another 68 volunteers were
      utilized to develop normative ranges for CFV(fast) and CFV(slow). KEY RESULTS: A
      distinct change in velocity could be determined in all 36 barium swallows with
      the fast and slow contractile segments having a median velocity of 4.2 cm s(-1)
      and 1.0 cm s(-1), respectively. The CDP noted on OPT correlated closely with
      formation of the phrenic ampulla making CFV(fast) (mean 5.1 cm s(-1)) correspond
      closely to peristaltic propagation and CFV(slow) (mean 1.7 cm s(-1)) to ampullary
      emptying. CONCLUSIONS & INFERENCES: The deceleration point in the CFV on OPT
      plots accurately demarcated the early region in which the CFV reflects
      peristaltic velocity (CFV(fast)) from the later region where it reflects the
      progression of ampullary emptying (CFV(slow)). These distinctions should help
      objectify definitions of disordered peristalsis, especially spasm, and improve
      understanding of impaired bolus transit across the oesophagogastric junction.

PMID- 20047639
TI  - Upper gastrointestinal motility changes following spinal cord injury.
AB  - Spinal cord injury (SCI) is associated with severe autonomic dysfunction in both
      the acute and chronic phases. Upper gastrointestinal (GI) motor dysfunction has
      been previously reported in humans and rats. Gastric emptying (GE) of a solid
      meal--as measured by the [(13)C]-octanoic acid breath test--is delayed in the
      first 3 weeks after either spinal cord transection (SCT) or contusion (SCC) in
      rats. This is one of the main findings of a new paper by Qualls-Creekmore et al.
      in the current issue of this journal. Previous studies in rats only reported
      impairment of GE, intestinal and GI transit of liquid after SCI, but the authors
      observed that the delay of the GE of solid was more prominent after SCT than SCC.
      Recovery of the delay of GE of solid occurred at 6 weeks after SCC, but not after
      SCT. However, gastric motility changes persisted despite the functional
      normalization of the GE in rats with SCC. Bowel dysfunction is a major physical
      and psychological burden for SCI patients. Collaborative efforts, like the
      development of international standards to evaluate autonomic function after SCI
      will likely clarify the mechanisms of dysfunction and lead to the development of
      new therapeutic strategies.

PMID- 20047640
TI  - Recent advances on the non-classical major histocompatibility complex class I HLA
      G molecule.
AB  - The human leukocyte antigen (HLA)-G non-classical major histocompatibility
      complex (MHC) class I molecule was originally described in first-trimester
      trophoblasts at the fetal-maternal interface in 1990. Eight years later, the
      First International Conference on this molecule was inaugurated by Prof Jean
      Dausset, recipient of the Nobel Prize in Medicine. The Fifth International
      Conference on HLA-G, held in Paris on July 2009, began with a tribute to Prof
      Jean Dausset who left us recently. This conference was co-chaired by Dr Edgardo
      D. Carosella and Prof Hans Grosse-Wilde, included 57 oral presentations and was
      attended by approximately 140 delegates from 16 countries. We summarize here the
      major advances on the HLA-G molecule that were reported, including findings on
      its biological activity and characterization of new mechanisms of action, notably
      through mesenchymal stem cells and regulatory cells, and the previously
      unexplored role of HLA-G on immune cells such as gammadelta T-cells and B
      lymphocytes. Furthermore, the role of HLA-G during pregnancy was revisited and
      its impact in pathologies such as cancer, autoimmune disorders and
      transplantation was further extended.

PMID- 20047641
TI  - Sequencing of a new HLA-DRB1*16 allele (DRB1*1615) with valine at residue 86.
AB  - Human leukocyte antigen (HLA)-DRB1*1615 shows one amino acid replacement at codon
      86 (G>V) regarding DRB1*160101.

PMID- 20047642
TI  - HLA-B*4907 and B*490101 differs by residue 163 placed in a dominant serologic
      epitope.
AB  - Human leukocyte antigen (HLA)-B*4907 was detected in a family from Morocco
      because of inconsistencies found between molecular and serologic typing results.
      B*4907 differs from B*490101 by two nucleotide changes in codon 163, producing an
      amino acid replacement, L>E.

PMID- 20047643
TI  - Norwegian Sami differs significantly from other Norwegians according to their HLA
      profile.
AB  - This study reports extensive genomic data for both human leukocyte antigen (HLA)
      class I and II loci in Norwegian Sami, a native population living in the
      northwest of Europe. The Sami have a distinct culture and their own languages,
      which belong to the Uralic linguistic family. Norwegian Sami (n = 200) were typed
      at the DNA level for the HLA-A, -C, -B, -DRB1 and -DQB1 loci, and compared with a
      non-Sami Norwegian population (n = 576). The two populations exhibited some
      common genetic features but also differed significantly at all HLA loci. The most
      significantly deviating allele frequencies were an increase of HLA-A*03, -B*27, 
      DRB1*08 and -DQB1*04 and a decrease of HLA-A*01, C*01, -DRB1*04 and -DQB1*02
      among Sami compared with non-Sami Norwegians. The Sami showed no deviation from
      Hardy-Weinberg equilibrium. The hypothesis of selective neutrality was rejected
      at all loci except for the A- and C- loci for the Sami. HLA haplotype frequencies
      also differed between the two populations. The most common extended HLA
      haplotypes were A*02-B*27-C*01-DR*08-DQB1*04 in the Sami and A*01-B*08-C*07-DR*03
      DQB1*02 in the other Norwegians. Genetic distance analyses indicated that the
      Norwegian Sami were highly differentiated from other Europeans and were most
      closely related to Finns whose language also belongs to the Uralic linguistic
      family. In conclusion, the Norwegian Sami and the non-Sami Norwegians were
      significantly different at all HLA loci. Our results can be explained by the fact
      that the two populations have different origins and that the Sami population has
      remained smaller and more isolated than its neighbors.

PMID- 20047644
TI  - A new DQA1 allele (DQA1*0510) in a Spanish celiac disease patient.
AB  - Human leukocyte antigen (HLA)-DQA1*0510 has been identified in a Spanish patient
      diagnosed with celiac disease. DQA1*0510 differs from DQA1*0505/09 by a point
      mutation at exon 2 producing an amino acid replacement at codon 77 (I>V).

PMID- 20047645
TI  - Evolutionary history of DLA class II haplotypes in canine diabetes mellitus
      through single nucleotide polymorphism genotyping.
AB  - Strong linkage disequilibrium (LD) is a characteristic of the major
      histocompatibility complex (MHC) region, as well as the genome in general in dogs
      as a consequence of demographic changes with domestication. Disease association
      studies of MHC haplotypes may be affected by high LD and the resultant shared
      genetic backgrounds of haplotypes giving associations with linked but non
      causative mutations, and also by convergent haplotypes, in which combinations of
      alleles have arisen independently. This study provides preliminary tools for dog
      leukocyte antigen (DLA) class II haplotype analysis with 102 single nucleotide
      polymorphisms (SNPs) identified in 14.6 kb and genotyping of 20 of these SNPs to
      tag haplotypes in 60 dogs with diabetes mellitus and in 49 non-diabetic dogs. The
      pattern of LD and analysis of SNP patterns indicated combinations of exon 2
      alleles have arisen through both recombination and convergence. For exon 2
      haplotypes associated with susceptibility or protection from diabetes mellitus, a
      region of fixed differences in SNPs across the DQ region was observed, suggesting
      a region outside exon 2 may be implicated in disease association. Four new DQB1
      promoter alleles restricted to diabetic dogs were identified, as well as a
      substitution difference in the X1 box of the DQB1 promoter that will potentially
      modify the effect of the protective haplotypes within diabetic dogs.

PMID- 20047646
TI  - The Pin 1 inhibitor juglone attenuates kidney fibrogenesis via Pin 1-independent
      mechanisms in the unilateral ureteral occlusion model.
AB  - BACKGROUND: Pin 1 is a peptidyl-prolyl isomerase inhibitor related to cyclophilin
      A and FK506 binding protein (FKBP). Juglone (5-hydroxy-1,4-naphthoquinone) is a
      natural inhibitor of Pin 1 with anti-inflammatory and antifibrotic properties. We
      evaluated the role of Pin 1 in renal fibrogenesis by evaluating the effects of
      juglone on epithelial to mesenchymal transition (EMT) and fibrogenesis in the rat
      unilateral ureteral obstruction (UUO) model and normal rat tubular epithelial
      cells (NRK52E). RESULTS: After 2 weeks of UUO, immunoblot analyses demonstrated
      that juglone (0.25 and 1 mg/kg/24 h) inhibited the deposition of matrix (alpha
      smooth muscle actin (SMA), collagen type III and vimentin) and the activation of
      signaling pathways involved in fibrogenesis (phospho-smad2) and stress response
      (phospho-heat shock protein (HSP)27). Juglone also reduced EMT (alpha-SMA and E
      cadherin dual staining) and oxidative stress (Mn superoxide dismutase (SOD) and
      NAPDH oxidase 2 (Nox-2) dual staining) in the obstructed kidney. There was no
      difference in Pin 1 levels between treatment and control groups. Pin 1 activity
      was significantly decreased in obstructed kidneys regardless of treatment status.
      In vitro, juglone (1 muM) significantly decreased alpha-SMA and p-smad levels
      compared to vehicle. CONCLUSIONS: Juglone attenuates fibrogenesis via Pin 1
      independent mechanisms in the UUO model. The antifibrotic effects of juglone may
      result from the inhibition of smad2 and oxidative stress.

PMID- 20047649
TI  - Amino acid "little Big Bang": representing amino acid substitution matrices as
      dot products of Euclidian vectors.
AB  - BACKGROUND: Sequence comparisons make use of a one-letter representation for
      amino acids, the necessary quantitative information being supplied by the
      substitution matrices. This paper deals with the problem of finding a
      representation that provides a comprehensive description of amino acid intrinsic
      properties consistent with the substitution matrices. RESULTS: We present a
      Euclidian vector representation of the amino acids, obtained by the singular
      value decomposition of the substitution matrices. The substitution matrix entries
      correspond to the dot product of amino acid vectors. We apply this vector
      encoding to the study of the relative importance of various amino acid
      physicochemical properties upon the substitution matrices. We also characterize
      and compare the PAM and BLOSUM series substitution matrices. CONCLUSIONS: This
      vector encoding introduces a Euclidian metric in the amino acid space, consistent
      with substitution matrices. Such a numerical description of the amino acid is
      useful when intrinsic properties of amino acids are necessary, for instance,
      building sequence profiles or finding consensus sequences, using machine learning
      algorithms such as Support Vector Machine and Neural Networks algorithms.

PMID- 20047647
TI  - Standing variation and new mutations both contribute to a fast response to
      selection for flowering time in maize inbreds.
AB  - BACKGROUND: In order to investigate the rate and limits of the response to
      selection from highly inbred genetic material and evaluate the respective
      contribution of standing variation and new mutations, we conducted a divergent
      selection experiment from maize inbred lines in open-field conditions during 7
      years. Two maize commercial seed lots considered as inbred lines, F252 and
      MBS847, constituted two biological replicates of the experiment. In each
      replicate, we derived an Early and a Late population by selecting and selfing the
      earliest and the latest individuals, respectively, to produce the next
      generation. RESULTS: All populations, except the Early MBS847, responded to
      selection despite a short number of generations and a small effective population
      size. Part of the response can be attributed to standing genetic variation in the
      initial seed lot. Indeed, we identified one polymorphism initially segregating in
      the F252 seed lot at a candidate locus for flowering time, which explained 35% of
      the trait variation within the Late F252 population. However, the model that best
      explained our data takes into account both residual polymorphism in the initial
      seed lots and a constant input of heritable genetic variation by new
      (epi)mutations. Under this model, values of mutational heritability range from
      0.013 to 0.025, and stand as an upper bound compare to what is reported in other
      species. CONCLUSIONS: Our study reports a long-term divergent selection
      experiment for a complex trait, flowering time, conducted on maize in open-field
      conditions. Starting from a highly inbred material, we created within a few
      generations populations that strikingly differ from the initial seed lot for
      flowering time while preserving most of the phenotypic characteristics of the
      initial inbred. Such material is unique for studying the dynamics of the response
      to selection and its determinants. In addition to the fixation of a standing
      beneficial mutation associated with a large phenotypic effect, a constant input
      of genetic variance by new mutations has likely contributed to the response. We
      discuss our results in the context of the evolution and mutational dynamics of
      populations characterized by a small effective population size.

PMID- 20047650
TI  - Evaluation of ammonia fibre expansion (AFEX) pretreatment for enzymatic
      hydrolysis of switchgrass harvested in different seasons and locations.
AB  - BACKGROUND: When producing biofuels from dedicated feedstock, agronomic factors
      such as harvest time and location can impact the downstream production. Thus,
      this paper studies the effectiveness of ammonia fibre expansion (AFEX)
      pretreatment on two harvest times (July and October) and ecotypes/locations (Cave
      in-Rock (CIR) harvested in Michigan and Alamo harvested in Alabama) for
      switchgrass (Panicum virgatum). RESULTS: Both harvest date and ecotype/location
      determine the pretreatment conditions that produce maximum sugar yields. There
      was a high degree of correlation between glucose and xylose released regardless
      of the harvest, pretreatment conditions, or enzyme formulation. Enzyme
      formulation that produced maximum sugar yields was the same across all harvests
      except for the CIR October harvest. The least mature sample, the July harvest of
      CIR switchgrass, released the most sugars (520 g/kg biomass) during enzymatic
      hydrolysis while requiring the least severe pretreatment conditions. In contrast,
      the most mature harvest released the least amount of sugars (410 g/kg biomass).
      All hydrolysates were highly fermentable, although xylose utilisation in the July
      CIR hydrolysate was poor. CONCLUSIONS: Each harvest type and location responded
      differently to AFEX pretreatment, although all harvests successfully produced
      fermentable sugars. Thus, it is necessary to consider an integrated approach
      between agricultural production and biochemical processing in order to insure
      optimal productivity.

PMID- 20047651
TI  - The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in
      Xenopus laevis.
AB  - BACKGROUND: The neural crest is a unique population of cells that arise in the
      vertebrate ectoderm at the neural plate border after which they migrate
      extensively throughout the embryo, giving rise to a wide range of derivatives. A
      number of proteins involved in neural crest development have dynamic expression
      patterns, and it is becoming clear that ubiquitin-mediated protein degradation is
      partly responsible for this. RESULTS: Here we demonstrate a novel role for the F
      box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus
      laevis Cdc4 were identified, and designated xCdc4alpha and xCdc4beta. These are
      highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are
      functionally equivalent in terms of their ability to degrade Cyclin E, an
      established vertebrate Cdc4 target. Blocking xCdc4 function specifically
      inhibited neural crest development at an early stage, prior to expression of c
      Myc, Snail2 and Snail. CONCLUSIONS: We demonstrate that Cdc4, an ubiquitin E3
      ligase subunit previously identified as targeting primarily cell cycle regulators
      for proteolysis, has additional roles in control of formation of the neural
      crest. Hence, we identify Cdc4 as a protein with separable but complementary
      functions in control of cell proliferation and differentiation.

PMID- 20047652
TI  - Knowledge transfer for the management of dementia:  a cluster randomised trial of
      blended learning in general practice.
AB  - BACKGROUND: The implementation of new medical knowledge into general practice is
      a complex process. Blended learning may offer an effective and efficient
      educational intervention to reduce the knowledge-to-practice gap. The aim of this
      study was to compare knowledge acquisition about dementia management between a
      blended learning approach using online modules in addition to quality circles
      (QCs) and QCs alone. METHODS: In this cluster-randomised trial with QCs as
      clusters and general practitioners (GPs) as participants, 389 GPs from 26 QCs in
      the western part of Germany were invited to participate. Data on the GPs'
      knowledge were obtained at three points in time by means of a questionnaire
      survey. Primary outcome was the knowledge gain before and after the
      interventions. A subgroup analysis of the users of the online modules was
      performed. RESULTS: 166 GPs were available for analysis and filled out a
      knowledge test at least two times. A significant increase of knowledge was found
      in both groups that indicated positive learning effects of both approaches.
      However, there was no significant difference between the groups. A subgroup
      analysis of the GPs who self-reported that they had actually used the online
      modules showed that they had a significant increase in their knowledge scores.
      CONCLUSION: A blended learning approach was not superior to a QCs approach for
      improving knowledge about dementia management. However, a subgroup of GPs who
      were motivated to actually use the online modules had a gain in knowledge. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN36550981.

PMID- 20047653
TI  - Modular titanium alloy neck adapter failures in hip replacement--failure mode
      analysis and influence of implant material.
AB  - BACKGROUND: Modular neck adapters for hip arthroplasty stems allow the surgeon to
      modify CCD angle, offset and femoral anteversion intraoperatively. Fretting or
      crevice corrosion may lead to failure of such a modular device due to high loads
      or surface contamination inside the modular coupling. Unfortunately we have
      experienced such a failure of implants and now report our clinical experience
      with the failures in order to advance orthopaedic material research and joint
      replacement surgery.The failed neck adapters were implanted between August 2004
      and November 2006 a total of about 5000 devices. After this period, the titanium
      neck adapters were replaced by adapters out of cobalt-chromium. Until the end of
      2008 in total 1.4% (n = 68) of the implanted titanium alloy neck adapters failed
      with an average time of 2.0 years (0.7 to 4.0 years) postoperatively. All, but
      one, patients were male, their average age being 57.4 years (36 to 75 years) and
      the average weight 102.3 kg (75 to 130 kg). The failures of neck adapters were
      divided into 66% with small CCD of 130 degrees and 60% with head lengths of L or
      larger. Assuming an average time to failure of 2.8 years, the cumulative failure
      rate was calculated with 2.4%. METHODS: A series of adapter failures of titanium
      alloy modular neck adapters in combination with a titanium alloy modular short
      hip stem was investigated. For patients having received this particular implant
      combination risk factors were identified which were associated with the
      occurRence of implant failure. A Kaplan-Meier survival-failure-analysis was
      conducted. The retrieved implants were analysed using microscopic and chemical
      methods. Modes of failure were simulated in biomechanical tests. Comparative
      tests included modular neck adapters made of titanium alloy and cobalt chrome
      alloy material. RESULTS: Retrieval examinations and biomechanical simulation
      revealed that primary micromotions initiated fretting within the modular tapered
      neck connection. A continuous abrasion and repassivation process with a
      subsequent cold welding at the titanium alloy modular interface. Surface layers
      of 10 - 30 microm titanium oxide were observed. Surface cracks caused by fretting
      or fretting corrosion finally lead to fatigue fracture of the titanium alloy
      modular neck adapters. Neck adapters made of cobalt chrome alloy show
      significantly reduced micromotions especially in case of contaminated cone
      connection. With a cobalt-chromium neck the micromotions can be reduced by a
      factor of 3 compared to the titanium neck. The incidence of fretting corrosion
      was also substantially lower with the cobalt-chromium neck configuration.
      CONCLUSIONS: Failure of modular titanium alloy neck adapters can be initiated by
      surface micromotions due to surface contamination or highly loaded implant
      components. In the present study, the patients at risk were men with an average
      weight over 100 kg. Modular cobalt chrome neck adapters provide higher safety
      compared to titanium alloy material.

PMID- 20047654
TI  - Identification of genes differentially expressed during interaction of resistant
      and susceptible apple cultivars (Malus x domestica) with Erwinia amylovora.
AB  - BACKGROUND: The necrogenic enterobacterium, Erwinia amylovora is the causal agent
      of the fire blight (FB) disease in many Rosaceae species, including apple and
      pear. During the infection process, the bacteria induce an oxidative stress
      response with kinetics similar to those induced in an incompatible bacteria-plant
      interaction. No resistance mechanism to E. amylovora in host plants has yet been
      characterized, recent work has identified some molecular events which occur in
      resistant and/or susceptible host interaction with E. amylovora: In order to
      understand the mechanisms that characterize responses to FB, differentially
      expressed genes were identified by cDNA-AFLP analysis in resistant and
      susceptible apple genotypes after inoculation with E. amylovora. RESULTS: cDNA
      were isolated from M.26 (susceptible) and G.41 (resistant) apple tissues
      collected 2 h and 48 h after challenge with a virulent E. amylovora strain or
      mock (buffer) inoculated. To identify differentially expressed transcripts,
      electrophoretic banding patterns were obtained from cDNAs. In the AFLP
      experiments, M.26 and G.41 showed different patterns of expression, including
      genes specifically induced, not induced, or repressed by E. amylovora. In total,
      190 ESTs differentially expressed between M.26 and G.41 were identified using 42
      pairs of AFLP primers. cDNA-AFLP analysis of global EST expression in a resistant
      and a susceptible apple genotype identified different major classes of genes. EST
      sequencing data showed that genes linked to resistance, encoding proteins
      involved in recognition, signaling, defense and apoptosis, were modulated by E.
      amylovora in its host plant. The expression time course of some of these ESTs
      selected via a bioinformatic analysis has been characterized. CONCLUSION: These
      data are being used to develop hypotheses of resistance or susceptibility
      mechanisms in Malus to E. amylovora and provide an initial categorization of
      genes possibly involved in recognition events, early signaling responses the
      subsequent development of resistance or susceptibility. These data also provided
      potential candidates for improving apple resistance to fire blight either by
      marker-assisted selection or genetic engineering.

PMID- 20047655
TI  - The BridgeDb framework: standardized access to gene, protein and metabolite
      identifier mapping services.
AB  - BACKGROUND: Many complementary solutions are available for the identifier mapping
      problem. This creates an opportunity for bioinformatics tool developers. Tools
      can be made to flexibly support multiple mapping services or mapping services
      could be combined to get broader coverage. This approach requires an interface
      layer between tools and mapping services. RESULTS: Here we present BridgeDb, a
      software framework for gene, protein and metabolite identifier mapping. This
      framework provides a standardized interface layer through which bioinformatics
      tools can be connected to different identifier mapping services. This approach
      makes it easier for tool developers to support identifier mapping. Mapping
      services can be combined or merged to support multi-omics experiments or to
      integrate custom microarray annotations. BridgeDb provides its own ready-to-go
      mapping services, both in webservice and local database forms. However, the
      framework is intended for customization and adaptation to any identifier mapping
      service. BridgeDb has already been integrated into several bioinformatics
      applications. CONCLUSION: By uncoupling bioinformatics tools from mapping
      services, BridgeDb improves capability and flexibility of those tools. All
      described software is open source and available at http://www.bridgedb.org.

PMID- 20047656
TI  - A computational screen for site selective A-to-I editing detects novel sites in
      neuron specific Hu proteins.
AB  - BACKGROUND: Several bioinformatic approaches have previously been used to find
      novel sites of ADAR mediated A-to-I RNA editing in human. These studies have
      discovered thousands of genes that are hyper-edited in their non-coding intronic
      regions, especially in alu retrotransposable elements, but very few substrates
      that are site-selectively edited in coding regions. Known RNA edited substrates
      suggest, however, that site selective A-to-I editing is particularly important
      for normal brain development in mammals. RESULTS: We have compiled a screen that
      enables the identification of new sites of site-selective editing, primarily in
      coding sequences. To avoid hyper-edited repeat regions, we applied our screen to
      the alu-free mouse genome. Focusing on the mouse also facilitated better
      experimental verification. To identify candidate sites of RNA editing, we first
      performed an explorative screen based on RNA structure and genomic sequence
      conservation. We further evaluated the results of the explorative screen by
      determining which transcripts were enriched for A-G mismatches between the
      genomic template and the expressed sequence since the editing product, inosine
      (I), is read as guanosine (G) by the translational machinery. For expressed
      sequences, we only considered coding regions to focus entirely on re-coding
      events. Lastly, we refined the results from the explorative screen using a novel
      scoring scheme based on characteristics for known A-to-I edited sites. The extent
      of editing in the final candidate genes was verified using total RNA from mouse
      brain and 454 sequencing. CONCLUSIONS: Using this method, we identified and
      confirmed efficient editing at one site in the Gabra3 gene. Editing was also
      verified at several other novel sites within candidates predicted to be edited.
      Five of these sites are situated in genes coding for the neuron-specific RNA
      binding proteins HuB and HuD.

PMID- 20047657
TI  - Refining transcriptional regulatory networks using network evolutionary models
      and gene histories.
AB  - BACKGROUND: Computational inference of transcriptional regulatory networks
      remains a challenging problem, in part due to the lack of strong network models.
      In this paper we present evolutionary approaches to improve the inference of
      regulatory networks for a family of organisms by developing an evolutionary model
      for these networks and taking advantage of established phylogenetic relationships
      among these organisms. In previous work, we used a simple evolutionary model and
      provided extensive simulation results showing that phylogenetic information,
      combined with such a model, could be used to gain significant improvements on the
      performance of current inference algorithms. RESULTS: In this paper, we extend
      the evolutionary model so as to take into account gene duplications and losses,
      which are viewed as major drivers in the evolution of regulatory networks. We
      show how to adapt our evolutionary approach to this new model and provide
      detailed simulation results, which show significant improvement on the reference
      network inference algorithms. Different evolutionary histories for gene
      duplications and losses are studied, showing that our adapted approach is
      feasible under a broad range of conditions. We also provide results on biological
      data (cis-regulatory modules for 12 species of Drosophila), confirming our
      simulation results.

PMID- 20047658
TI  - Constructing majority-rule supertrees.
AB  - BACKGROUND: Supertree methods combine the phylogenetic information from multiple
      partially-overlapping trees into a larger phylogenetic tree called a supertree.
      Several supertree construction methods have been proposed to date, but most of
      these are not designed with any specific properties in mind. Recently, Cotton and
      Wilkinson proposed extensions of the majority-rule consensus tree method to the
      supertree setting that inherit many of the appealing properties of the former.
      RESULTS: We study a variant of one of Cotton and Wilkinson's methods, called
      majority-rule (+) supertrees. After proving that a key underlying problem for
      constructing majority-rule (+) supertrees is NP-hard, we develop a polynomial
      size exact integer linear programming formulation of the problem. We then present
      a data reduction heuristic that identifies smaller subproblems that can be solved
      independently. While this technique is not guaranteed to produce optimal
      solutions, it can achieve substantial problem-size reduction. Finally, we report
      on a computational study of our approach on various real data sets, including the
      121-taxon, 7-tree Seabirds data set of Kennedy and Page. CONCLUSIONS: The results
      indicate that our exact method is computationally feasible for moderately large
      inputs. For larger inputs, our data reduction heuristic makes it feasible to
      tackle problems that are well beyond the range of the basic integer programming
      approach. Comparisons between the results obtained by our heuristic and exact
      solutions indicate that the heuristic produces good answers. Our results also
      suggest that the majority-rule (+) approach, in both its basic form and with data
      reduction, yields biologically meaningful phylogenies.

PMID- 20047659
TI  - Phylogenetic comparative assembly.
AB  - BACKGROUND: Recent high throughput sequencing technologies are capable of
      generating a huge amount of data for bacterial genome sequencing projects.
      Although current sequence assemblers successfully merge the overlapping reads,
      often several contigs remain which cannot be assembled any further. It is still
      costly and time consuming to close all the gaps in order to acquire the whole
      genomic sequence. RESULTS: Here we propose an algorithm that takes several
      related genomes and their phylogenetic relationships into account to create a
      graph that contains the likelihood for each pair of contigs to be adjacent.
      Subsequently, this graph can be used to compute a layout graph that shows the
      most promising contig adjacencies in order to aid biologists in finishing the
      complete genomic sequence. The layout graph shows unique contig orderings where
      possible, and the best alternatives where necessary. CONCLUSIONS: Our new
      algorithm for contig ordering uses sequence similarity as well as phylogenetic
      information to estimate adjacencies of contigs. An evaluation of our
      implementation shows that it performs better than recent approaches while being
      much faster at the same time.

PMID- 20047660
TI  - Mimosa: mixture model of co-expression to detect modulators of regulatory
      interaction.
AB  - BACKGROUND: Functionally related genes tend to be correlated in their expression
      patterns across multiple conditions and/or tissue-types. Thus co-expression
      networks are often used to investigate functional groups of genes. In particular,
      when one of the genes is a transcription factor (TF), the co-expression-based
      interaction is interpreted, with caution, as a direct regulatory interaction.
      However, any particular TF, and more importantly, any particular regulatory
      interaction, is likely to be active only in a subset of experimental conditions.
      Moreover, the subset of expression samples where the regulatory interaction holds
      may be marked by presence or absence of a modifier gene, such as an enzyme that
      post-translationally modifies the TF. Such subtlety of regulatory interactions is
      overlooked when one computes an overall expression correlation. RESULTS: Here we
      present a novel mixture modeling approach where a TF-Gene pair is presumed to be
      significantly correlated (with unknown coefficient) in an (unknown) subset of
      expression samples. The parameters of the model are estimated using a Maximum
      Likelihood approach. The estimated mixture of expression samples is then mined to
      identify genes potentially modulating the TF-Gene interaction. We have validated
      our approach using synthetic data and on four biological cases in cow, yeast, and
      humans. CONCLUSIONS: While limited in some ways, as discussed, the work
      represents a novel approach to mine expression data and detect potential
      modulators of regulatory interactions.

PMID- 20047661
TI  - Fast prediction of RNA-RNA interaction.
AB  - BACKGROUND: Regulatory antisense RNAs are a class of ncRNAs that regulate gene
      expression by prohibiting the translation of an mRNA by establishing stable
      interactions with a target sequence. There is great demand for efficient
      computational methods to predict the specific interaction between an ncRNA and
      its target mRNA(s). There are a number of algorithms in the literature which can
      predict a variety of such interactions--unfortunately at a very high
      computational cost. Although some existing target prediction approaches are much
      faster, they are specialized for interactions with a single binding site.
      METHODS: In this paper we present a novel algorithm to accurately predict the
      minimum free energy structure of RNA-RNA interaction under the most general type
      of interactions studied in the literature. Moreover, we introduce a fast
      heuristic method to predict the specific (multiple) binding sites of two
      interacting RNAs. RESULTS: We verify the performance of our algorithms for joint
      structure and binding site prediction on a set of known interacting RNA pairs.
      Experimental results show our algorithms are highly accurate and outperform all
      competitive approaches.

PMID- 20047662
TI  - Back-translation for discovering distant protein homologies in the presence of
      frameshift mutations.
AB  - BACKGROUND: Frameshift mutations in protein-coding DNA sequences produce a
      drastic change in the resulting protein sequence, which prevents classic protein
      alignment methods from revealing the proteins' common origin. Moreover, when a
      large number of substitutions are additionally involved in the divergence, the
      homology detection becomes difficult even at the DNA level. RESULTS: We developed
      a novel method to infer distant homology relations of two proteins, that accounts
      for frameshift and point mutations that may have affected the coding sequences.
      We design a dynamic programming alignment algorithm over memory-efficient graph
      representations of the complete set of putative DNA sequences of each protein,
      with the goal of determining the two putative DNA sequences which have the best
      scoring alignment under a powerful scoring system designed to reflect the most
      probable evolutionary process. Our implementation is freely available at
      [http://bioinfo.lifl.fr/path/]. CONCLUSIONS: Our approach allows to uncover
      evolutionary information that is not captured by traditional alignment methods,
      which is confirmed by biologically significant examples.

PMID- 20047663
TI  - Linear-time protein 3-D structure searching with insertions and deletions.
AB  - BACKGROUND: Two biomolecular 3-D structures are said to be similar if the RMSD
      (root mean square deviation) between the two molecules' sequences of 3-D
      coordinates is less than or equal to some given constant bound. Tools for
      searching for similar structures in biomolecular 3-D structure databases are
      becoming increasingly important in the structural biology of the post-genomic
      era. RESULTS: We consider an important, fundamental problem of reporting all
      substructures in a 3-D structure database of chain molecules (such as proteins)
      which are similar to a given query 3-D structure, with consideration of indels
      (i.e., insertions and deletions). This problem has been believed to be very
      difficult but its exact computational complexity has not been known. In this
      paper, we first prove that the problem in unbounded dimensions is NP-hard. We
      then propose a new algorithm that dramatically improves the average-case time
      complexity of the problem in 3-D in case the number of indels k is bounded by a
      constant. Our algorithm solves the above problem for a query of size m and a
      database of size N in average-case O(N) time, whereas the time complexity of the
      previously best algorithm was O(Nm(k+1)). CONCLUSIONS: Our results show that
      although the problem of searching for similar structures in a database based on
      the RMSD measure with indels is NP-hard in the case of unbounded dimensions, it
      can be solved in 3-D by a simple average-case linear time algorithm when the
      number of indels is bounded by a constant.

PMID- 20047664
TI  - A simulation study comparing supertree and combined analysis methods using
      SMIDGen.
AB  - BACKGROUND: Supertree methods comprise one approach to reconstructing large
      molecular phylogenies given multi-marker datasets: trees are estimated on each
      marker and then combined into a tree (the "supertree") on the entire set of taxa.
      Supertrees can be constructed using various algorithmic techniques, with the most
      common being matrix representation with parsimony (MRP). When the data allow, the
      competing approach is a combined analysis (also known as a "supermatrix" or
      "total evidence" approach) whereby the different sequence data matrices for each
      of the different subsets of taxa are concatenated into a single supermatrix, and
      a tree is estimated on that supermatrix. RESULTS: In this paper, we describe an
      extensive simulation study we performed comparing two supertree methods, MRP and
      weighted MRP, to combined analysis methods on large model trees. A key
      contribution of this study is our novel simulation methodology (Super-Method
      Input Data Generator, or SMIDGen) that better reflects biological processes and
      the practices of systematists than earlier simulations. We show that combined
      analysis based upon maximum likelihood outperforms MRP and weighted MRP, giving
      especially big improvements when the largest subtree does not contain most of the
      taxa. CONCLUSIONS: This study demonstrates that MRP and weighted MRP produce
      distinctly less accurate trees than combined analyses for a given base method
      (maximum parsimony or maximum likelihood). Since there are situations in which
      combined analyses are not feasible, there is a clear need for better supertree
      methods. The source tree and combined datasets used in this study can be used to
      test other supertree and combined analysis methods.

PMID- 20047665
TI  - A tree-based method for the rapid screening of chemical fingerprints.
AB  - BACKGROUND: The fingerprint of a molecule is a bitstring based on its structure,
      constructed such that structurally similar molecules will have similar
      fingerprints. Molecular fingerprints can be used in an initial phase of drug
      development for identifying novel drug candidates by screening large databases
      for molecules with fingerprints similar to a query fingerprint. RESULTS: In this
      paper, we present a method which efficiently finds all fingerprints in a database
      with Tanimoto coefficient to the query fingerprint above a user defined
      threshold. The method is based on two novel data structures for rapid screening
      of large databases: the kD grid and the Multibit tree. The kD grid is based on
      splitting the fingerprints into k shorter bitstrings and utilising these to
      compute bounds on the similarity of the complete bitstrings. The Multibit tree
      uses hierarchical clustering and similarity within each cluster to compute
      similar bounds. We have implemented our method and tested it on a large real
      world data set. Our experiments show that our method yields approximately a three
      fold speed-up over previous methods. CONCLUSIONS: Using the novel kD grid and
      Multibit tree significantly reduce the time needed for searching databases of
      fingerprints. This will allow researchers to (1) perform more searches than
      previously possible and (2) to easily search large databases.

PMID- 20047666
TI  - QTLs and candidate genes for desiccation and abscisic acid content in maize
      kernels.
AB  - BACKGROUND: Kernel moisture at harvest is an important trait since a low value is
      required to prevent unexpected early germination and ensure seed preservation. It
      is also well known that early germination occurs in viviparous mutants, which are
      impaired in abscisic acid (ABA) biosynthesis. To provide some insight into the
      genetic determinism of kernel desiccation in maize, quantitative trait loci
      (QTLs) were detected for traits related to kernel moisture and ABA content in
      both embryo and endosperm during kernel desiccation. In parallel, the expression
      and mapping of genes involved in kernel desiccation and ABA biosynthesis, were
      examined to detect candidate genes. RESULTS: The use of an intermated recombinant
      inbred line population allowed for precise QTL mapping. For 29 traits examined in
      an unreplicated time course trial of days after pollination, a total of 78 QTLs
      were detected, 43 being related to kernel desiccation, 15 to kernel weight and 20
      to ABA content. Multi QTL models explained 35 to 50% of the phenotypic variation
      for traits related to water status, indicating a large genetic control amenable
      to breeding. Ten of the 20 loci controlling ABA content colocated with previously
      detected QTLs controlling water status and ABA content in water stressed leaves.
      Mapping of candidate genes associated with kernel desiccation and ABA
      biosynthesis revealed several colocations between genes with putative functions
      and QTLs. Parallel investigation via RT-PCR experiments showed that the
      expression patterns of the ABA-responsive Rab17 and Rab28 genes as well as the
      late embryogenesis abundant Emb5 and aquaporin genes were related to desiccation
      rate and parental allele effect. Database searches led to the identification and
      mapping of two zeaxanthin epoxidase (ZEP) and five novel 9-cis-epoxycarotenoid
      dioxygenase (NCED) related genes, both gene families being involved in ABA
      biosynthesis. The expression of these genes appeared independent in the embryo
      and endosperm and not correlated with ABA content in either tissue. CONCLUSIONS:
      A high resolution QTL map for kernel desiccation and ABA content in embryo and
      endosperm showed several precise colocations between desiccation and ABA traits.
      Five new members of the maize NCED gene family and another maize ZEP gene were
      identified and mapped. Among all the identified candidates, aquaporins and
      members of the Responsive to ABA gene family appeared better candidates than
      NCEDs and ZEPs.

PMID- 20047667
TI  - A markov classification model for metabolic pathways.
AB  - BACKGROUND: This paper considers the problem of identifying pathways through
      metabolic networks that relate to a specific biological response. Our proposed
      model, HME3M, first identifies frequently traversed network paths using a Markov
      mixture model. Then by employing a hierarchical mixture of experts, separate
      classifiers are built using information specific to each path and combined into
      an ensemble prediction for the response. RESULTS: We compared the performance of
      HME3M with logistic regression and support vector machines (SVM) for both
      simulated pathways and on two metabolic networks, glycolysis and the pentose
      phosphate pathway for Arabidopsis thaliana. We use AltGenExpress microarray data
      and focus on the pathway differences in the developmental stages and stress
      responses of Arabidopsis. The results clearly show that HME3M outperformed the
      comparison methods in the presence of increasing network complexity and pathway
      noise. Furthermore an analysis of the paths identified by HME3M for each
      metabolic network confirmed known biological responses of Arabidopsis.
      CONCLUSIONS: This paper clearly shows HME3M to be an accurate and robust method
      for classifying metabolic pathways. HME3M is shown to outperform all comparison
      methods and further is capable of identifying known biologically active pathways
      within microarray data.

PMID- 20047668
TI  - Efficient algorithms for analyzing segmental duplications  with deletions and
      inversions in genomes.
AB  - BACKGROUND: Segmental duplications, or low-copy repeats, are common in mammalian
      genomes.  In the human genome, most segmental duplications are mosaics comprised
      of multiple duplicated fragments. This complex genomic organization complicates
      analysis of the evolutionary history of these sequences.   One model proposed to
      explain this mosaic patterns is a model of repeated aggregation and subsequent
      duplication of genomic sequences. RESULTS: We describe a polynomial-time exact
      algorithm to compute duplication distance, a genomic distance defined as the most
      parsimonious way to build a target string by repeatedly copying substrings of a
      fixed source string.  This distance models the process of repeated aggregation
      and duplication.   We also describe extensions of this distance to include
      certain types of substring deletions and inversions.  Finally, we provide a
      description of a sequence of duplication events as a context-free grammar (CFG).
      CONCLUSION: These new genomic distances will permit more biologically realistic
      analyses of segmental duplications in genomes.

PMID- 20047670
TI  - A simple, practical and complete O(n3/log n)-time algorithm for RNA folding using
      the Four-Russians speedup.
AB  - BACKGROUND: The problem of computationally predicting the secondary structure (or
      folding) of RNA molecules was first introduced more than thirty years ago and yet
      continues to be an area of active research and development. The basic RNA-folding
      problem of finding a maximum cardinality, non-crossing, matching of complimentary
      nucleotides in an RNA sequence of length n, has an O(n3)-time dynamic programming
      solution that is widely applied. It is known that an o(n3) worst-case time
      solution is possible, but the published and suggested methods are complex and
      have not been established to be practical. Significant practical improvements to
      the original dynamic programming method have been introduced, but they retain the
      O(n3) worst-case time bound when n is the only problem-parameter used in the
      bound. Surprisingly, the most widely-used, general technique to achieve a worst
      case (and often practical) speed up of dynamic programming, the Four-Russians
      technique, has not been previously applied to the RNA-folding problem. This is
      perhaps due to technical issues in adapting the technique to RNA-folding.
      RESULTS: In this paper, we give a simple, complete, and practical Four-Russians
      algorithm for the basic RNA-folding problem, achieving a worst-case time-bound of
      O(n3/log(n)). CONCLUSIONS: We show that this time-bound can also be obtained for
      richer nucleotide matching scoring-schemes, and that the method achieves
      consistent speed-ups in practice. The contribution is both theoretical and
      practical, since the basic RNA-folding problem is often solved multiple times in
      the inner-loop of more complex algorithms, and for long RNA molecules in the
      study of RNA virus genomes.

PMID- 20047669
TI  - FlexSnap: flexible non-sequential protein structure alignment.
AB  - BACKGROUND: Proteins have evolved subject to energetic selection pressure for
      stability and flexibility. Structural similarity between proteins that have gone
      through conformational changes can be captured effectively if flexibility is
      considered. Topologically unrelated proteins that preserve secondary structure
      packing interactions can be detected if both flexibility and Sequential
      permutations are considered. We propose the FlexSnap algorithm for flexible non
      topological protein structural alignment. RESULTS: The effectiveness of FlexSnap
      is demonstrated by measuring the agreement of its alignments with manually
      curated non-sequential structural alignments. FlexSnap showed competitive results
      against state-of-the-art algorithms, like DALI, SARF2, MultiProt, FlexProt, and
      FATCAT. Moreover on the DynDom dataset, FlexSnap reported longer alignments with
      smaller rmsd. CONCLUSIONS: We have introduced FlexSnap, a greedy chaining
      algorithm that reports both sequential and non-sequential alignments and allows
      twists (hinges). We assessed the quality of the FlexSnap alignments by measuring
      its agreements with manually curated non-sequential alignments. On the FlexProt
      dataset, FlexSnap was competitive to state-of-the-art flexible alignment methods.
      Moreover, we demonstrated the benefits of introducing hinges by showing
      significant improvements in the alignments reported by FlexSnap for the structure
      pairs for which rigid alignment methods reported alignments with either low
      coverage or large rmsd. AVAILABILITY: An implementation of the FlexSnap algorithm
      will be made available online at http://www.cs.rpi.edu/~zaki/software/flexsnap.

PMID- 20047671
TI  - Phylogenetic footprinting of non-coding RNA: hammerhead ribozyme sequences in a
      satellite DNA family of Dolichopoda cave crickets (Orthoptera, Rhaphidophoridae).
AB  - BACKGROUND: The great variety in sequence, length, complexity, and abundance of
      satellite DNA has made it difficult to ascribe any function to this genome
      component. Recent studies have shown that satellite DNA can be transcribed and be
      involved in regulation of chromatin structure and gene expression. Some satellite
      DNAs, such as the pDo500 sequence family in Dolichopoda cave crickets, have a
      catalytic hammerhead (HH) ribozyme structure and activity embedded within each
      repeat. RESULTS: We assessed the phylogenetic footprints of the HH ribozyme
      within the pDo500 sequences from 38 different populations representing 12 species
      of Dolichopoda. The HH region was significantly more conserved than the non
      hammerhead (NHH) region of the pDo500 repeat. In addition, stems were more
      conserved than loops. In stems, several compensatory mutations were detected that
      maintain base pairing. The core region of the HH ribozyme was affected by very
      few nucleotide substitutions and the cleavage position was altered only once
      among 198 sequences. RNA folding of the HH sequences revealed that a potentially
      active HH ribozyme can be found in most of the Dolichopoda populations and
      species. CONCLUSIONS: The phylogenetic footprints suggest that the HH region of
      the pDo500 sequence family is selected for function in Dolichopoda cave crickets.
      However, the functional role of HH ribozymes in eukaryotic organisms is unclear.
      The possible functions have been related to trans cleavage of an RNA target by a
      ribonucleoprotein and regulation of gene expression. Whether the HH ribozyme in
      Dolichopoda is involved in similar functions remains to be investigated. Future
      studies need to demonstrate how the observed nucleotide changes and evolutionary
      constraint have affected the catalytic efficiency of the hammerhead.

PMID- 20047672
TI  - A randomised controlled trial and cost-effectiveness evaluation of "booster"
      interventions to sustain increases in physical activity in middle-aged adults in
      deprived urban neighbourhoods.
AB  - BACKGROUND: Systematic reviews have identified a range of brief interventions
      which increase physical activity in previously sedentary people. There is an
      absence of evidence about whether follow up beyond three months can maintain long
      term physical activity. This study assesses whether it is worth providing
      motivational interviews, three months after giving initial advice, to those who
      have become more active. METHODS/DESIGN: Study candidates (n = 1500) will
      initially be given an interactive DVD and receive two telephone follow ups at
      monthly intervals checking on receipt and use of the DVD. Only those that have
      increased their physical activity after three months (n = 600) will be randomised
      into the study. These participants will receive either a "mini booster" (n =
      200), "full booster" (n = 200) or no booster (n = 200). The "mini booster"
      consists of two telephone calls one month apart to discuss physical activity and
      maintenance strategies. The "full booster" consists of a face-to-face meeting
      with the facilitator at the same intervals. The purpose of these booster sessions
      is to help the individual maintain their increase in physical activity.
      Differences in physical activity, quality of life and costs associated with the
      booster interventions, will be measured three and nine months from randomisation.
      The research will be conducted in 20 of the most deprived neighbourhoods in
      Sheffield, which have large, ethnically diverse populations, high levels of
      economic deprivation, low levels of physical activity, poorer health and shorter
      life expectancy. Participants will be recruited through general practices and
      community groups, as well as by postal invitation, to ensure the participation of
      minority ethnic groups and those with lower levels of literacy. Sheffield City
      Council and Primary Care Trust fund a range of facilities and activities to
      promote physical activity and variations in access to these between
      neighbourhoods will make it possible to examine whether the effectiveness of the
      intervention is modified by access to community facilities. A one-year integrated
      feasibility study will confirm that recruitment targets are achievable based on a
      10% sample. DISCUSSION: The choice of study population, study interventions,
      brief intervention preceding the study, and outcome measure are discussed. TRIAL
      REGISTRATION: Current Controlled Trials: ISRCTN56495859; ClinicalTrials.gov:
      NCT00836459.

PMID- 20047674
TI  - The Plasmodium falciparum merozoite surface protein-1 19 KD antibody response in
      the Peruvian Amazon predominantly targets the non-allele specific, shared sites
      of this antigen.
AB  - BACKGROUND: Plasmodium falciparum re-emerged in Iquitos, Peru in 1994 and is now
      hypoendemic (< 0.5 infections/person/year). Purportedly non-immune individuals
      with discrete (non-overlapping) P. falciparum infections can be followed using
      this population dynamic. Previous work demonstrated a strong association between
      this population's antibody response to PfMSP1-19KD and protection against febrile
      illness and parasitaemia. Therefore, some selection for PfMSP1-19KD allelic
      diversity would be expected if the protection is to allele-specific sites of
      PfMSP1-19KD. Here, the potential for allele-specific polymorphisms in this
      population is investigated, and the allele-specificity of antibody responses to
      PfMSP1-19KD are determined. METHODS: The 42KD region in PfMSP1 was genotyped from
      160 individual infections collected between 2003 and 2007. Additionally, the
      polymorphic block 2 region of Pfmsp1 (Pfmsp1-B2) was genotyped in 781 infection
      months to provide a baseline for population-level diversity. To test whether
      PfMSP1-19KD genetic diversity had any impact on antibody responses, ELISAs
      testing IgG antibody response were performed on individuals using all four allele
      types of PfMSP1-19KD. An antibody depletion ELISA was used to test the ability of
      antibodies to cross-react between allele-types. RESULTS: Despite increased
      diversity in Pfmsp1-B2, limited diversity within Pfmsp1-42KD was observed. All
      160 infections genotyped were Mad20-like at the Pfmsp1-33KD locus. In the Pfmsp1
      19KD locus, 159 (99.4%) were the Q-KSNG-F haplotype and 1 (0.6%) was the E-KSNG-L
      haplotype. Antibody responses in 105 individuals showed that Q-KNG and Q-TSR
      alleles generated the strongest immune responses, while Q-KNG and E-KNG responses
      were more concordant with each other than with those from Q-TSR and E-TSR, and
      vice versa. The immuno-depletion ELISAs showed all samples responded to the
      antigenic sites shared amongst all allelic forms of PfMSP1-19KD. CONCLUSIONS: A
      non-allele specific antibody response in PfMSP1-19KD may explain why other
      allelic forms have not been maintained or evolved in this population. This has
      important implications for the use of PfMSP1-19KD as a vaccine candidate. It is
      possible that Peruvians have increased antibody responses to the shared sites of
      PfMSP1-19KD, either due to exposure/parasite characteristics or due to a human
      genetic predisposition. Alternatively, these allelic polymorphisms are not immune
      specific even in other geographic regions, implying these polymorphisms may be
      less important in immune evasion that previous studies suggest.

PMID- 20047673
TI  - Genomic characterization of the Yersinia genus.
AB  - BACKGROUND: New DNA sequencing technologies have enabled detailed comparative
      genomic analyses of entire genera of bacterial pathogens. Prior to this study,
      three species of the enterobacterial genus Yersinia that cause invasive human
      diseases (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia
      enterocolitica) had been sequenced. However, there were no genomic data on the
      Yersinia species with more limited virulence potential, frequently found in soil
      and water environments. RESULTS: We used high-throughput sequencing-by-synthesis
      instruments to obtain 25- to 42-fold average redundancy, whole-genome shotgun
      data from the type strains of eight species: Y. aldovae, Y. bercovieri, Y.
      frederiksenii, Y. kristensenii, Y. intermedia, Y. mollaretii, Y. rohdei, and Y.
      ruckeri. The deepest branching species in the genus, Y. ruckeri, causative agent
      of red mouth disease in fish, has the smallest genome (3.7 Mb), although it
      shares the same core set of approximately 2,500 genes as the other members of the
      species, whose genomes range in size from 4.3 to 4.8 Mb. Yersinia genomes had a
      similar global partition of protein functions, as measured by the distribution of
      Cluster of Orthologous Groups families. Genome to genome variation in islands
      with genes encoding functions such as ureases, hydrogenases and B-12 cofactor
      metabolite reactions may reflect adaptations to colonizing specific host
      habitats. CONCLUSIONS: Rapid high-quality draft sequencing was used successfully
      to compare pathogenic and non-pathogenic members of the Yersinia genus. This work
      underscores the importance of the acquisition of horizontally transferred genes
      in the evolution of Y. pestis and points to virulence determinants that have been
      gained and lost on multiple occasions in the history of the genus.

PMID- 20047675
TI  - Understanding how education/support groups help lone mothers.
AB  - BACKGROUND: Lone-mother led families are at increased risk of psychosocial
      disadvantage, social isolation and mental health morbidity. Community-based
      programs are more accessible for families seeking assistance. We examine the
      experiences of eight lone mothers participating in a larger randomized controlled
      trial (RCT) of a community-based education/support group program using mixed
      methods. METHODS: A purposeful sample of eight mothers participating in the
      intervention arm of an RCT of community-based support/education groups was
      selected for the qualitative study. Individual interviews asked mothers about
      themselves and their relationships with their children before and after the
      group. Interviews were taped, transcribed and content analysis was used to code
      and interpret the data. Quantitative data collected in the RCT were used to
      describe these mothers. RESULTS: Mothers participating in the RCT and qualitative
      study experienced multiple difficulties, including financial and mood problems.
      These mothers reported that before participating in the group, they had shared
      experiences of social isolation, stigma, a sense of failure, poor relationships
      with their children and difficulties with financial management. After the group,
      mothers identified improved self-esteem, support from other mothers, improved
      parenting skills and improved communication with their children as outcomes of
      group participation. CONCLUSIONS: The qualitative data revealed mothers'
      perceptions of specific areas that improved by participating in the group. The
      utility of complementary information provided by qualitative and quantitative
      methods in understanding program impact, as well as the need for broader
      assistance is noted.

PMID- 20047676
TI  - Random pharmacokinetic profiles of EC-MPS in children with autoimmune disease.
AB  - BACKGROUND: : Therapy with mycophenolate mofetil (MMF) has become a valuable
      therapeutic option in children with autoimmune disease. MMF prescription in
      children with autoimmune diseases differs from that in transplant recipients in
      terms of different dosing regimen, and concomitant administration of other
      immunosuppressive medications. Recently, another formulation of the same active
      compound, mycophenolic acid (MPA), has become available as enteric-coated
      Mycophenolate Sodium (EC-MPS).  Dosing and pharmacokinetics of EC-MPS in
      pediatric autoimmune disease have never been studied. METHOD: S: We therefore
      performed a pilot study on 6 patients, who were treated with EC-MPS. All patients
      underwent 1-2 full 10-point pharmacokinetic (PK) profiles over a 12-hour dosing
      interval. We compared the results with that of 22 similar patients on MMF
      therapy. RESULTS: : Median EC-MPS dose was 724 mg/m2 (range 179-933 mg/m2). The
      MPA Area-Under-The-(Time-Concentration)-Curves (AUCs) on MMF and EC-MPS were
      comparable (54.4 mg x h/L on MMF and 44.0 mg x h/L on EC-MPS, n.s., Mann
      Whitney). After correcting for bioequivalence, the dose-normalized AUCs were also
      similar on both the formulations. However, PK profiles on EC-MPS were quite
      random, and time to maximum concentration varied from 30 minutes to 720 minutes.
      The concentration at six-hour correlated best with the AUC. This was different
      from a homogenous PK-profile on MPA. CONCLUSIONS: : EC-MPS has a different PK
      profile from MMF. The data suggest that patients on EC-MPS must undergo a
      complete PK profile to assess adequate exposure. The 6-hour concentration
      provides an estimate of the exposure and should be targeted between 3-4 mg/L.

PMID- 20047677
TI  - Predictors of health decline in older adults with pneumonia: findings from the
      Community Acquired Pneumonia Impact Study.
AB  - BACKGROUND: The purpose of this study was to identify predictors of health
      decline among older adults with clinically diagnosed community acquired pneumonia
      (CAP). It was hypothesized that older adults with CAP who had lower levels of
      social support would be more likely to report a decline in health. METHODS: A
      telephone survey was used to collect detailed information from older adults about
      their experiences with CAP. A broader determinants of health framework was used
      to guide data collection. This was a community wide study with participants being
      recruited from all radiology clinics in one Ontario community. RESULTS: The most
      important predictors of a health decline included: two symptoms (no energy;
      diaphoresis), two lifestyle variables (being very active; allowing people to
      smoke in their home), one quality of life variable (little difficulty in doing
      usual daily activities) and one social support variable (having siblings).
      CONCLUSIONS: A multiplicity of factors was found to be associated with a decline
      in health among older adults with clinically diagnosed CAP. These findings may be
      useful to physicians, family caregivers and others for screening older adults and
      providing interventions to help ensure positive health outcomes.

PMID- 20047679
TI  - Assessing agreement between malaria slide density readings.
AB  - BACKGROUND: Several criteria have been used to assess agreement between replicate
      slide readings of malaria parasite density. Such criteria may be based on percent
      difference, or absolute difference, or a combination. Neither the rationale for
      choosing between these types of criteria, nor that for choosing the magnitude of
      difference which defines acceptable agreement, are clear. The current paper seeks
      a procedure which avoids the disadvantages of these current options and whose
      parameter values are more clearly justified. METHODS AND RESULTS: Variation of
      parasite density within a slide is expected, even when it has been prepared from
      a homogeneous sample. This places lower limits on sensitivity and observer
      agreement, quantified by the Poisson distribution. This means that, if a
      criterion of fixed percent difference criterion is used for satisfactory
      agreement, the number of discrepant readings is over-estimated at low parasite
      densities. With a criterion of fixed absolute difference, the same happens at
      high parasite densities. For an ideal slide, following the Poisson distribution,
      a criterion based on a constant difference in square root counts would apply for
      all densities. This can be back-transformed to a difference in absolute counts,
      which, as expected, gives a wider range of acceptable agreement at higher average
      densities. In an example dataset from Tanzania, observed differences in square
      root counts correspond to a 95% limits of agreement of -2,800 and +2,500
      parasites/microl at average density of 2,000 parasites/microl, and -6,200 and
      +5,700 parasites/microl at 10,000 parasites/microl. However, there were more
      outliers beyond those ranges at higher densities, meaning that actual coverage of
      these ranges was not a constant 95%, but decreased with density. In a second
      study, a trial of microscopist training, the corresponding ranges of agreement
      are wider and asymmetrical: -8,600 to +5,200/microl, and -19,200 to
      +11,700/microl, respectively. By comparison, the optimal limits of agreement,
      corresponding to Poisson variation, are +/- 780 and +/- 1,800 parasites/microl,
      respectively. The focus of this approach on the volume of blood read leads to
      other conclusions. For example, no matter how large a volume of blood is read,
      some densities are too low to be reliably detected, which in turn means that
      disagreements on slide positivity may simply result from within-slide variation,
      rather than reading errors. CONCLUSIONS: The proposed method defines limits of
      acceptable agreement in a way which allows for the natural increase in
      variability with parasite density. This includes defining the levels of between
      reader variability, which are consistent with random variation: disagreements
      within these limits should not trigger additional readings. This approach merits
      investigation in other settings, in order to determine both the extent of its
      applicability, and appropriate numerical values for limits of agreement.

PMID- 20047678
TI  - Complete genome sequence of the fire blight pathogen Erwinia pyrifoliae DSM
      12163T and comparative genomic insights into plant pathogenicity.
AB  - BACKGROUND: Erwinia pyrifoliae is a newly described necrotrophic pathogen, which
      causes fire blight on Asian (Nashi) pear and is geographically restricted to
      Eastern Asia. Relatively little is known about its genetics compared to the
      closely related main fire blight pathogen E. amylovora. RESULTS: The genome of
      the type strain of E. pyrifoliae strain DSM 12163T, was sequenced using both 454
      and Solexa pyrosequencing and annotated. The genome contains a circular
      chromosome of 4.026 Mb and four small plasmids. Based on their respective role in
      virulence in E. amylovora or related organisms, we identified several putative
      virulence factors, including type III and type VI secretion systems and their
      effectors, flagellar genes, sorbitol metabolism, iron uptake determinants, and
      quorum-sensing components. A deletion in the rpoS gene covering the most
      conserved region of the protein was identified which may contribute to the
      difference in virulence/host-range compared to E. amylovora. Comparative genomics
      with the pome fruit epiphyte Erwinia tasmaniensis Et1/99 showed that both species
      are overall highly similar, although specific differences were identified, for
      example the presence of some phage gene-containing regions and a high number of
      putative genomic islands containing transposases in the E. pyrifoliae DSM 12163T
      genome. CONCLUSIONS: The E. pyrifoliae genome is an important addition to the
      published genome of E. tasmaniensis and the unfinished genome of E. amylovora
      providing a foundation for re-sequencing additional strains that may shed light
      on the evolution of the host-range and virulence/pathogenicity of this important
      group of plant-associated bacteria.

PMID- 20047680
TI  - Extensive analysis of D-J-C arrangements allows the identification of different
      mechanisms enhancing the diversity in sheep T cell receptor beta-chain
      repertoire.
AB  - BACKGROUND: In most species of mammals, the TRB locus has the common feature of a
      library of TRBV genes positioned at the 5'- end of two in tandem aligned D-J-C
      gene clusters, each composed of a single TRBD gene, 6-7 TRBJ genes and one TRBC
      gene. An enhancer located at the 3'end of the last TRBC and a well-defined
      promoter situated at the 5'end of the TRBD gene and/or a undefined promoter
      situated at the 5'end of the TRBD2 are sufficient to generate the full
      recombinase accessibility at the locus. In ruminant species, the 3'end of the TRB
      locus is characterized by the presence of three D-J-C clusters, each constituted
      by a single TRBD, 5-7 TRBJ and one TRBC genes with the center cluster showing a
      structure combined with the clusters upstream and downstream, suggesting that a
      unequal crossover occurred in the duplication. An enhancer downstream the last
      TRBC, and a promoter at the 5'-end of each TRBD gene are also present. RESULTS:
      In this paper we focused our attention on the analysis of a large number of sheep
      TR beta-chain transcripts derived from four different lymphoid tissues of three
      diverse sheep breed animals to certify the use and frequency of the three gene
      clusters in the beta-chain repertoire. As the sheep TRB locus genomic
      organization is known, the exact interpretation of the V-D-J rearrangements was
      fully determined. Our results clearly demonstrate that sheep beta-chain
      constitutes a level of variability that is substantially larger than that
      described in other mammalian species. This is due not only to the increase of the
      number of D and J genes available to the somatic recombination, but also to the
      presence of the trans-rearrangement process. Moreover, the functional complexity
      of beta-chain repertoire is resolved by other mechanisms such as alternative cis-
      and trans-splicing and recombinational diversification that seems to affect the
      variety of the constant region. CONCLUSION: All together our data demonstrate
      that a disparate set of molecular mechanisms operate to perform a diversified
      repertoire in the sheep beta-chain and this could confer some special biological
      properties to the corresponding alphabeta T cells in the ruminant lineage.

PMID- 20047681
TI  - Owner reports of attention, activity, and impulsivity in dogs: a replication
      study.
AB  - BACKGROUND: When developing behaviour measurement tools that use third party
      assessments, such as parent report, it is important to demonstrate reliability of
      resulting scales through replication using novel cohorts. The domestic dog has
      been suggested as a model to investigate normal variation in attention,
      hyperactivity, and impulsive behaviours impaired in Attention Deficit Hyperactive
      Disorder (ADHD). The human ADHD Rating Scale, modified for dogs and using owner
      directed surveys, was applied in a European sample. We asked whether findings
      would be replicated utilizing an Internet survey in a novel sample, where
      unassisted survey completion, participant attitudes and breeds might affect
      previous findings. METHODS: Using a slightly modified version of the prior
      survey, we collected responses (n = 1030, 118 breeds representing 7 breed groups)
      primarily in the United States and Canada. This study was conducted using an
      Internet survey mechanism. RESULTS: Reliability analyses confirmed two scales
      previously identified for dogs (inattention [IA], hyperactivity-impulsivity [HA
      IM]). Models including age, training status, and breed group accounted for very
      little variance in subscales, with no effect of gender. CONCLUSIONS: The factor
      invariance demonstrated in these findings confirms that owner report, using this
      modified human questionnaire, provides dog scores according to "inattention" and
      "hyperactivity-impulsivity" axes. Further characterization of naturally occurring
      variability of attention, activity, and impulsivity in domestic dogs may provide
      insight into genetic backgrounds underlying behaviours impaired in attention and
      associated disorders.

PMID- 20047682
TI  - Analysis of newly established EST databases reveals similarities between heart
      regeneration in newt and fish.
AB  - BACKGROUND: The newt Notophthalmus viridescens possesses the remarkable ability
      to respond to cardiac damage by formation of new myocardial tissue. Surprisingly
      little is known about changes in gene activities that occur during the course of
      regeneration. To begin to decipher the molecular processes, that underlie
      restoration of functional cardiac tissue, we generated an EST database from
      regenerating newt hearts and compared the transcriptional profile of selected
      candidates with genes deregulated during zebrafish heart regeneration. RESULTS: A
      cDNA library of 100,000 cDNA clones was generated from newt hearts 14 days after
      ventricular injury. Sequencing of 11520 cDNA clones resulted in 2894 assembled
      contigs. BLAST searches revealed 1695 sequences with potential homology to
      sequences from the NCBI database. BLAST searches to TrEMBL and Swiss-Prot
      databases assigned 1116 proteins to Gene Ontology terms. We also identified a
      relatively large set of 174 ORFs, which are likely to be unique for urodele
      amphibians. Expression analysis of newt-zebrafish homologues confirmed the
      deregulation of selected genes during heart regeneration. Sequences, BLAST
      results and GO annotations were visualized in a relational web based database
      followed by grouping of identified proteins into clusters of GO Terms. Comparison
      of data from regenerating zebrafish hearts identified biological processes, which
      were uniformly overrepresented during cardiac regeneration in newt and zebrafish.
      CONCLUSION: We concluded that heart regeneration in newts and zebrafish led to
      the activation of similar sets of genes, which suggests that heart regeneration
      in both species might follow similar principles. The design of the newly
      established newt EST database allows identification of molecular pathways
      important for heart regeneration.

PMID- 20047683
TI  - Effects of low power laser irradiation on bone healing in animals: a meta
      analysis.
AB  - PURPOSE: The meta-analysis was performed to identify animal research defining the
      effects of low power laser irradiation on biomechanical indicators of bone
      regeneration and the impact of dosage. METHODS: We searched five electronic
      databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised
      Clinical Trials) for studies in the area of laser and bone healing published from
      1966 to October 2008. Included studies had to investigate fracture healing in any
      animal model, using any type of low power laser irradiation, and use at least one
      quantitative biomechanical measures of bone strength. There were 880 abstracts
      related to the laser irradiation and bone issues (healing, surgery and
      assessment). Five studies met our inclusion criteria and were critically
      appraised by two raters independently using a structured tool designed for rating
      the quality of animal research studies. After full text review, two articles were
      deemed ineligible for meta-analysis because of the type of injury method and
      biomechanical variables used, leaving three studies for meta-analysis. Maximum
      bone tolerance force before the point of fracture during the biomechanical test,
      4 weeks after bone deficiency was our main biomechanical bone properties for the
      Meta analysis. RESULTS: Studies indicate that low power laser irradiation can
      enhance biomechanical properties of bone during fracture healing in animal
      models. Maximum bone tolerance was statistically improved following low level
      laser irradiation (average random effect size 0.726, 95% CI 0.08-1.37, p 0.028).
      While conclusions are limited by the low number of studies, there is concordance
      across limited evidence that laser improves the strength of bone tissue during
      the healing process in animal models.

PMID- 20047684
TI  - Long-term follow-up of beryllium sensitized workers from a single employer.
AB  - BACKGROUND: Up to 12% of beryllium-exposed American workers would test positive
      on beryllium lymphocyte proliferation test (BeLPT) screening, but the
      implications of sensitization remain uncertain. METHODS: Seventy two current and
      former employees of a beryllium manufacturer, including 22 with pathologic
      changes of chronic beryllium disease (CBD), and 50 without, with a confirmed
      positive test were followed-up for 7.4 +/-3.1 years. RESULTS: Beyond predicted
      effects of aging, flow rates and lung volumes changed little from baseline, while
      DLCO dropped 17.4% of predicted on average. Despite this group decline, only 8
      subjects (11.1%) demonstrated physiologic or radiologic abnormalities typical of
      CBD. Other than baseline status, no clinical or laboratory feature distinguished
      those who clinically manifested CBD at follow-up from those who did not.
      CONCLUSIONS: The clinical outlook remains favorable for beryllium-sensitized
      individuals over the first 5-12 years. However, declines in DLCO may presage
      further and more serious clinical manifestations in the future. These conclusions
      are tempered by the possibility of selection bias and other study limitations.

PMID- 20047685
TI  - Apyrase treatment of myocardial infarction according to a clinically applicable
      protocol fails to reduce myocardial injury in a porcine model.
AB  - BACKGROUND: Ectonucleotidase dependent adenosine generation has been implicated
      in preconditioning related cardioprotection against ischemia-reperfusion injury,
      and treatment with a soluble ectonucleotidase has been shown to reduce myocardial
      infarct size (IS) when applied prior to induction of ischemia. However,
      ectonucleotidase treatment according to a clinically applicable protocol, with
      administration only after induction of ischemia, has not previously been
      evaluated. We therefore investigated if treatment with the ectonucleotidase
      apyrase, according to a clinically applicable protocol, would reduce IS and
      microvascular obstruction (MO) in a large animal model. METHODS: A percutaneous
      coronary intervention balloon was inflated in the left anterior descending artery
      for 40 min, in 16 anesthetized pigs (40-50 kg). The pigs were randomized to 40
      min of 1 ml/min intracoronary infusion of apyrase (10 U/ml, n = 8) or saline (0.9
      mg/ml, n = 8), twenty minutes after balloon inflation. Area at risk (AAR) was
      evaluated by ex vivo SPECT. IS and MO were evaluated by ex vivo MRI. RESULTS: No
      differences were observed between the apyrase group and saline group with respect
      to IS/AAR (75.7 +/- 4.2% vs 69.4 +/- 5.0%, p = NS) or MO (10.7 +/- 4.8% vs 11.4
      +/- 4.8%, p = NS), but apyrase prolonged the post-ischemic reactive hyperemia.
      CONCLUSION: Apyrase treatment according to a clinically applicable protocol, with
      administration of apyrase after induction of ischemia, does not reduce myocardial
      infarct size or microvascular obstruction.

PMID- 20047686
TI  - The effectiveness of computerized clinical guidelines in the process of care: a
      systematic review.
AB  - BACKGROUND: Clinical practice guidelines have been developed aiming to improve
      the quality of care. The implementation of the computerized clinical guidelines
      (CCG) has been supported by the development of computerized clinical decision
      support systems.This systematic review assesses the impact of CCG on the process
      of care compared with non-computerized clinical guidelines. METHODS: Specific
      features of CCG were studied through an extensive search of scientific
      literature, querying electronic databases: Pubmed/Medline, Embase and Cochrane
      Controlled Trials Register. A multivariable logistic regression was carried out
      to evaluate the association of CCG's features with positive effect on the process
      of care. RESULTS: Forty-five articles were selected. The logistic model showed
      that Automatic provision of recommendation in electronic version as part of
      clinician workflow (Odds Ratio [OR]= 17.5; 95% confidence interval [CI]: 1.6
      193.7) and Publication Year (OR = 6.7; 95%CI: 1.3-34.3) were statistically
      significant predictors. CONCLUSIONS: From the research that has been carried out,
      we can conclude that after implementation of CCG significant improvements in
      process of care are shown. Our findings also suggest clinicians, managers and
      other health care decision makers which features of CCG might improve the
      structure of computerized system.

PMID- 20047687
TI  - Collagen V-induced nasal tolerance downregulates pulmonary collagen mRNA gene and
      TGF-beta expression in experimental systemic sclerosis.
AB  - BACKGROUND: The purpose of this study was to evaluate collagen deposition, mRNA
      collagen synthesis and TGF-beta expression in the lung tissue in an experimental
      model of scleroderma after collagen V-induced nasal tolerance. METHODS: Female
      New Zealand rabbits (N = 12) were immunized with 1 mg/ml of collagen V in
      Freund's adjuvant (IM). After 150 days, six immunized animals were tolerated by
      nasal administration of collagen V (25 microg/day) (IM-TOL) daily for 60 days.
      The collagen content was determined by morphometry, and mRNA expressions of types
      I, III and V collagen were determined by Real-time PCR. The TGF-beta expression
      was evaluated by immunostaining and quantified by point counting methods. To
      statistic analysis ANOVA with Bonferroni test were employed for multiple
      comparison when appropriate and the level of significance was determined to be p
      < 0.05. RESULTS: IM-TOL, when compared to IM, showed significant reduction in
      total collagen content around the vessels (0.371 +/- 0.118 vs. 0.874 +/- 0.282, p
      < 0.001), bronchioles (0.294 +/- 0.139 vs. 0.646 +/- 0.172, p < 0.001) and in the
      septal interstitium (0.027 +/- 0.014 vs. 0.067 +/- 0.039, p = 0.026). The lung
      tissue of IM-TOL, when compared to IM, showed decreased immunostaining of types
      I, III and V collagen, reduced mRNA expression of types I (0.10 +/- 0.07 vs. 1.0
      +/- 0.528, p = 0.002) and V (1.12 +/- 0.42 vs. 4.74 +/- 2.25, p = 0.009)
      collagen, in addition to decreased TGF-beta expression (p < 0.0001). CONCLUSIONS:
      Collagen V-induced nasal tolerance in the experimental model of SSc regulated the
      pulmonary remodeling process, inhibiting collagen deposition and collagen I and V
      mRNA synthesis. Additionally, it decreased TGF-beta expression, suggesting a
      promising therapeutic option for scleroderma treatment.

PMID- 20047688
TI  - Normal colon epithelium: a dataset for the analysis of gene expression and
      alternative splicing events in colon disease.
AB  - BACKGROUND: Studies using microarray analysis of colorectal cancer have been
      generally beleaguered by the lack of a normal cell population of the same lineage
      as the tumor cell. One of the main objectives of this study was to generate a
      reference gene expression data set for normal colonic epithelium which can be
      used in comparisons with diseased tissues, as well as to provide a dataset that
      could be used as a baseline for studies in alternative splicing. RESULTS: We
      present a dependable expression reference data set for non-neoplastic colonic
      epithelial cells. An enriched population of fresh colon epithelial cells were
      obtained from non-neoplastic, colectomy specimens and analyzed using Affymetrix
      GeneChip EXON 1.0 ST arrays. For demonstration purposes, we have compared the
      data derived from these cells to a publically available set of tumor and matched
      normal colon data. This analysis allowed an assessment of global gene expression
      alterations and demonstrated that adjacent normal tissues, with a high degree of
      cellular heterogeneity, are not always representative of normal cells for
      comparison to tumors which arise from the colon epithelium. We also examined
      alternative splicing events in tumors compared to normal colon epithelial cells.
      CONCLUSIONS: The findings from this study represent the first comprehensive
      expression profile for non-neoplastic colonic epithelial cells reported. Our
      analysis of splice variants illustrate that this is a very labor intensive
      procedure, requiring vigilant examination of the data. It is projected that the
      contribution of this set of data derived from pure colonic epithelial cells will
      enhance studies in colon-related disease and offer a vital baseline for studies
      aimed at elucidating the mechanisms of alternative splicing.

PMID- 20047689
TI  - Changes in neuronal activation patterns in response to androgen deprivation
      therapy: a pilot study.
AB  - BACKGROUND: A common treatment option for men with prostate cancer is androgen
      deprivation therapy (ADT). However, men undergoing ADT may experience physical
      side effects, changes in quality of life and sometimes psychiatric and cognitive
      side effects. METHODS: In this study, hormone naive patients without evidence of
      metastases with a rising PSA were treated with nine months of ADT. Functional
      magnetic resonance imaging (fMRI) of the brain during three visuospatial tasks
      was performed at baseline prior to treatment and after nine months of ADT in five
      subjects. Seven healthy control patients, underwent neuroimaging at the same time
      intervals. RESULTS: ADT patients showed reduced, task-related BOLD-fMRI
      activation during treatment that was not observed in control subjects. Reduction
      in activation in right parietal-occipital regions from baseline was observed
      during recall of the spatial location of objects and mental rotation.
      CONCLUSIONS: Findings, while preliminary, suggest that ADT reduces task-related
      neural activation in brain regions that are involved in mental rotation and
      accurate recall of spatial information.

PMID- 20047690
TI  - The Washington Needle Depot: fitting healthcare to injection drug users rather
      than injection drug users to healthcare: moving from a syringe exchange to
      syringe distribution model.
AB  - Needle exchange programs chase political as well as epidemiological dragons,
      carrying within them both implicit moral and political goals. In the exchange
      model of syringe distribution, injection drug users (IDUs) must provide used
      needles in order to receive new needles. Distribution and retrieval are co
      existent in the exchange model. Likewise, limitations on how many needles can be
      received at a time compel addicts to have multiple points of contact with
      professionals where the virtues of treatment and detox are impressed upon them.
      The centre of gravity for syringe distribution programs needs to shift from
      needle exchange to needle distribution, which provides unlimited access to
      syringes. This paper provides a case study of the Washington Needle Depot, a
      program operating under the syringe distribution model, showing that the
      distribution and retrieval of syringes can be separated with effective results.
      Further, the experience of IDUs is utilized, through paid employment, to provide
      a vulnerable population of people with clean syringes to prevent HIV and HCV.

PMID- 20047692
TI  - Cardiovascular magnetic resonance and PET-CT of left atrial paraganglioma.
AB  - Cardiac paragangliomas are among the rarest primary cardiac tumors. We present a
      case of left atrial paraganglioma in a patient who presented with symptoms and
      signs of catecholamine excess in which cardiovascular magnetic resonance in
      multiple orientations and PET-CT played an important role in the diagnosis and
      tissue characterization.

PMID- 20047691
TI  - Regulation of CCL2 and CCL3 expression in human brain endothelial cells by
      cytokines and lipopolysaccharide.
AB  - BACKGROUND: Chemokines are emerging as important mediators of CNS inflammation
      capable of activating leukocyte integrins and directing the migration of
      leukocyte subsets to sites of antigenic challenge. In this study we investigated
      the expression, release and binding of CCL2 (MCP-1) and CCL3 (MIP-1alpha) in an
      in vitro model of the human blood-brain barrier. METHODS: The kinetics of
      expression and cytokine upregulation and release of the beta-chemokines CCL2 and
      CCL3 were studied by immunocytochemistry and enzyme-linked immunosorbent assay in
      primary cultures of human brain microvessel endothelial cells (HBMEC). In
      addition, the differential binding of these chemokines to the basal and apical
      endothelial cell surfaces was assessed by immunoelectron microscopy. RESULTS:
      Untreated HBMEC synthesize and release low levels of CCL2. CCL3 is minimally
      expressed, but not released by resting HBMEC. Treatment with TNF-alpha, IL-1beta,
      LPS and a combination of TNF-alpha and IFN-gamma, but not IFN-gamma alone,
      significantly upregulated the expression and release of both chemokines in a time
      dependent manner. The released CCL2 and CCL3 bound to the apical and basal
      endothelial surfaces, respectively. This distribution was reversed in cytokine
      activated HBMEC resulting in a predominantly basal localization of CCL2 and
      apical distribution of CCL3. CONCLUSIONS: Since cerebral endothelial cells are
      the first resident CNS cells to contact circulating leukocytes, expression,
      release and presentation of CCL2 and CCL3 on cerebral endothelium suggests an
      important role for these chemokines in regulating the trafficking of inflammatory
      cells across the BBB in CNS inflammation.

PMID- 20047693
TI  - Citation analysis of orthopaedic literature; 18 major orthopaedic journals
      compared for Impact Factor and SCImago.
AB  - BACKGROUND: One of the disadvantages of the Impact Factor (IF) is self-citation.
      The SCImago Journal Rank (SJR) indicator excludes self-citations and considers
      the quality, rather than absolute numbers, of citations of a journal by other
      journals. The present study re-evaluated the influence of self-citation on the
      2007 IF for 18 major orthopaedic journals and investigated the difference in
      ranking between IF and SJR. METHODS: The journals were analysed for self-citation
      both overall and divided into a general group (n = 8) and a specialized group (n
      = 10). Self-cited and self-citing rates, as well as citation densities and IFs
      corrected for self-citation (cIF), were calculated. The rankings of the 18
      journals by IF and by SJR were compared and the absolute difference between these
      rankings (DeltaR) was determined. RESULTS: Specialized journals had higher self
      citing rates (p = 0.01, Deltamedian = 9.50, 95%CI -19.42 to 0.42), higher self
      cited rates (p = 0.0004, Deltamedian = -10.50, 95%CI -15.28 to -5.72) and greater
      differences between IF and cIF (p = 0.003, Deltamedian = 3.50, 95%CI -6.1 to
      13.1). There was no significant correlation between self-citing rate and IF for
      both groups (general: r = 0.46, p = 0.27; specialized: r = 0.21, p = 0.56). When
      the difference in ranking between IF and SJR was compared between both groups,
      sub-specialist journals were ranked lower compared to their general counterparts
      (DeltaR: p = 0.006, Deltamedian = 2.0, 95%CI -0.39 to 4.39). CONCLUSIONS:
      Citation analysis shows that specialized orthopaedic journals have specific self
      citation tendencies. The correlation between self-cited rate and IF in our sample
      was large but, due to small sample size, not significant. The SJR excludes self
      citations in its calculation and therefore enhances the underestimation in
      ranking of specialized journals.

PMID- 20047694
TI  - Long-term prognosis of diabetic patients with acute myocardial infarction in the
      era of acute revascularization.
AB  - BACKGROUND: The long-term prognosis of diabetic patients with acute myocardial
      infarction (AMI) treated by acute revascularization is uncertain, and the optimal
      pharmacotherapy for such cases has not been fully evaluated. METHODS: To
      elucidate the long-term prognosis and prognostic factors in diabetic patients
      with AMI, a prospective, cohort study involving 3021 consecutive AMI patients was
      conducted. All patients discharged alive from hospital were followed to monitor
      their prognosis every year. The primary endpoint of the study was all-cause
      mortality, and the secondary endpoint was the occurrence of major cardiovascular
      events. To elucidate the effect of various factors on the long-term prognosis of
      AMI patients with diabetes, the patients were divided into two groups matched by
      propensity scores and analyzed retrospectively. RESULTS: Diabetes was diagnosed
      in 1102 patients (36.5%). During the index hospitalization, coronary angioplasty
      and coronary thrombolysis were performed in 58.1% and 16.3% of patients,
      respectively. In-hospital mortality of diabetic patients with AMI was comparable
      to that of non-diabetic AMI patients (9.2% and 9.3%, respectively). In total,
      2736 patients (90.6%) were discharged alive and followed for a median of 4.2
      years (follow-up rate, 96.0%). The long-term survival rate was worse in the
      diabetic group than in the non-diabetic group, but not significantly different
      (hazard ratio, 1.20 [0.97-1.49], p = 0.09). On the other hand, AMI patients with
      diabetes showed a significantly higher incidence of cardiovascular events than
      the non-diabetic group (1.40 [1.20-1.64], p < 0.0001). Multivariate analysis
      revealed that three factors were significantly associated with favorable late
      outcomes in diabetic AMI patients: acute revascularization (HR, 0.62);
      prescribing aspirin (HR, 0.27); and prescribing renin-angiotensin system (RAS)
      inhibitors (HR, 0.53). There was no significant correlation between late outcome
      and prescription of beta-blockers (HR, 0.97) or calcium channel blockers (HR,
      1.27). Although standard Japanese-approved doses of statins were associated with
      favorable outcome in AMI patients with diabetes, this was not statistically
      significant (0.67 [0.39-1.06], p = 0.11). CONCLUSIONS: Although diabetic patients
      with AMI have more frequent adverse events than non-diabetic patients with AMI,
      the present results suggest that acute revascularization and standard therapy
      with aspirin and RAS inhibitors may improve their prognosis.

PMID- 20047695
TI  - Deep sequencing identifies novel and conserved microRNAs in peanuts (Arachis
      hypogaea L.).
AB  - BACKGROUND: MicroRNAs (miRNAs) are a new class of small, endogenous RNAs that
      play a regulatory role in the cell by negatively affecting gene expression at the
      post-transcriptional level. miRNAs have been shown to control numerous genes
      involved in various biological and metabolic processes. There have been extensive
      studies on discovering miRNAs and analyzing their functions in model species,
      such as Arabidopsis and rice. Increasing investigations have been performed on
      important agricultural crops including soybean, conifers, and Phaselous vulgaris
      but no studies have been reported on discovering peanut miRNAs using a cloning
      strategy. RESULTS: In this study, we employed the next generation high through
      put Solexa sequencing technology to clone and identify both conserved and species
      specific miRNAs in peanuts. Next generation high through-put Solexa sequencing
      showed that peanuts have a complex small RNA population and the length of small
      RNAs varied, 24-nt being the predominant length for a majority of the small RNAs.
      Combining the deep sequencing and bioinformatics, we discovered 14 novel miRNA
      families as well as 75 conserved miRNAs in peanuts. All 14 novel peanut miRNAs
      are considered to be species-specific because no homologs have been found in
      other plant species except ahy-miRn1, which has a homolog in soybean. qRT-PCR
      analysis demonstrated that both conserved and peanut-specific miRNAs are
      expressed in peanuts. CONCLUSIONS: This study led to the discovery of 14 novel
      and 22 conserved miRNA families from peanut. These results show that regulatory
      miRNAs exist in agronomically important peanuts and may play an important role in
      peanut growth, development, and response to environmental stress.

PMID- 20047696
TI  - Circumferential myocardial strain in cardiomyopathy with and without left bundle
      branch block.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to decrease
      mortality in 60-70% of advanced heart failure patients with left bundle branch
      block (LBBB) and QRS duration > 120 ms. There have been intense efforts to find
      reproducible non-invasive parameters to predict CRT response. We hypothesized
      that different left ventricular contraction patterns may exist in LBBB patients
      with depressed systolic function and applied tagged cardiovascular magnetic
      resonance (CMR) to assess circumferential strain in this population. METHODS: We
      determined myocardial circumferential strain at the basal, mid, and apical
      ventricular level in 35 subjects (10 with ischemic cardiomyopathy, 15 with non
      ischemic cardiomyopathy, and 10 healthy controls). Patterns of circumferential
      strain were analyzed. Time to peak systolic circumferential strain in each of the
      6 segments in all three ventricular slices and the standard deviation of time to
      peak strain in the basal and mid ventricular slices were determined. RESULTS:
      Dyskinesis of the anterior septum and the inferior septum in at least two
      ventricular levels was seen in 50% (5 out of 10) of LBBB patients while 30% had
      isolated dyskinesis of the anteroseptum, and 20% had no dyskinesis in any
      segments, similar to all of the non-LBBB patients and healthy controls. Peak
      circumferential strain shortening was significantly reduced in all cardiomyopathy
      patients at the mid-ventricular level (LBBB 9 +/- 6%, non-LBBB 10 +/- 4% vs.
      healthy 19 +/- 4%; both p < 0.0001 compared to healthy), but was similar among
      the LBBB and non-LBBB groups (p = 0.20). The LBBB group had significantly greater
      dyssynchrony compared to the non-LBBB group and healthy controls assessed by
      opposing wall delays and 12-segment standard deviation (LBBB 164 +/- 30 ms vs.
      non-LBBB 70 +/- 17 ms (p < 0.0001), non-LBBB vs. healthy 65 +/- 17 ms (p =
      0.47)). CONCLUSIONS: Septal dyskinesis exists in some patients with LBBB.
      Myocardial circumferential strain analysis enables detailed characterization of
      contraction patterns, strengths, and timing in cardiomyopathy patients with and
      without LBBB.

PMID- 20047697
TI  - Health-related quality of life among individuals with long-standing spinal cord
      injury: a comparative study of veterans and non-veterans.
AB  - BACKGROUND: Spinal cord-injured (SCI) patients experience poor health-related
      quality of life (HRQOL) and they usually report lower HRQOL than the general
      population or population subgroups in Iran and elsewhere. The aim of this study
      was to compare HRQOL between veterans and non-veterans with SCI in Iran. METHODS:
      This was a cross-sectional study. HRQOL was measured using the 36-item Short Form
      Health Survey (SF-36). Thirty-nine male veterans and 63 non-veteran males with
      SCI were included in the study. Regression analyses were applied to determine the
      variables affecting physical and mental health-related quality of life among the
      patients. RESULTS: The male veterans had a lower HRQOL than the non-veterans with
      SCI. The differences were significant for all measures except for physical and
      social functioning. The greatest difference was observed for bodily pain (P =
      0.001). The regression analysis results indicated that a longer time since injury
      was associated (P = 0.01) with better physical health-related quality of life
      (PCS), while being a veteran (P < 0.001) and having a spinal lesion in the
      cervical region (P = 0.001) were associated with poorer PCS. Older age (P <
      0.001) and higher education (P = 0.01) were associated with better mental health
      related quality of life (MCS), while being a veteran and having a spinal lesion
      in the cervical region (P = 0.02) were associated with poorer MCS. CONCLUSION:
      The study findings showed that veterans with SCI experienced lower HRQOL than
      their non-veteran counterparts. A qualitative study is recommended to evaluate
      why HRQOL was lower in veterans than in non-veterans with SCI although veterans
      had higher incomes as a result of their pensions and increased access to
      equipment, and medications. To improve quality of life in both veterans and non
      veterans with spinal cord injuries, policy changes or implementation of new
      interventions may be essential so that veterans could receive additional support
      (e.g. counseling, recreation therapy, vocational therapy, etc.) and non-veterans
      could meet their basic needs.

PMID- 20047698
TI  - A multicentric observational trial of pegylated liposomal doxorubicin for
      metastatic breast cancer.
AB  - BACKGROUND: Pegylated liposomal doxorubicin (PLD) is active in metastatic breast
      cancer. This observational study evaluated the efficacy and safety of PLD in
      patients treated during routine clinical practice. METHODS: Eligible patients had
      metastatic breast cancer and were treated with PLD according to the dose and
      schedule determined by their physician as part of routine practice. The primary
      objectives were to analyze the efficacy and toxicity of PLD therapy. RESULTS: 125
      patients were assessable. Median age was 62 years, 78% had performance status 0
      1, and 60% had estrogen-receptor-positive disease. PLD treatment was second- or
      third-line in 69% of patients. Prior anthracyclines (adjuvant or metastatic) had
      been used in 56% of patients. The majority of patients (79%) received PLD every 4
      weeks at a median dose of 40 mg/m2. Overall response rate was 43% in all patients
      and 34% in those previously treated with anthracyclines. The most common grade
      3/4 adverse events were skin toxicity/hand-foot syndrome (6%), and leukopenia
      (3%). CONCLUSIONS: This observational study supports the activity and
      tolerability of PLD in metastatic breast cancer as demonstrated in PLD clinical
      trials.

PMID- 20047699
TI  - [Neurological symptoms following lightening strike].
AB  - A 56-year-old man was referred to the neurological outpatients' department
      suffering from problems with walking and painful, burning feet after having been
      struck by lightning 6 months previously. He also experienced orthostatic symptoms
      and episodes of 'flushing' and was unable to tolerate contact with clothing or
      bed sheets on his lower legs or feet. After excluding other possible causes, the
      patient was diagnosed with 'polyneuropathy due to lightning strike'. Gabapentine
      had a favourable effect on the sensory symptoms. Lightening strikes are a rare
      cause of polyneuropathy.

PMID- 20047700
TI  - Molecular mechanisms underlying nutrient-stimulated incretin secretion.
AB  - The incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP) are released from enteroendocrine cells in the
      intestinal epithelium in response to nutrient ingestion. The actions of GLP-1 and
      GIP - not only on local gut physiology but also on glucose homeostasis, appetite
      control and fat metabolism - have made these hormones an attractive area for drug
      discovery programmes. The potential range of strategies to target the secretion
      of these hormones therapeutically has been limited by an incomplete understanding
      of the mechanisms underlying their release. The use of organ and whole-animal
      perfusion techniques, cell line models and primary L- and K-cells has led to the
      identification of a variety of pathways involved in the sensing of carbohydrate,
      fat and protein in the gut lumen. This review focuses on our current
      understanding of these signalling mechanisms that might underlie nutrient
      responsiveness of L- and K-cells.

PMID- 20047701
TI  - Predicting metabolisable energy in commercial rat diets: physiological fuel
      values may be misleading.
AB  - Knowledge about metabolisable energy (ME) intake is crucial for various
      experimental settings in rodent studies. ME considers faecal and renal energy
      losses. In particular, faecal energy excretion can vary considerably between
      differentially composed diets. Thus determination of faecal energy losses, i.e.
      apparent energy digestibility, is the most important experimental approach to
      determine ME. Predictive equations for ME such as Atwater factors or an equation
      for pigs, which are frequently employed for rodent feed, consider an average
      energy digestibility for nutrients and average renal losses for protein. Both
      equations, however, were never validated for rat feed. We therefore determined
      experimentally the digestibility of energy (experimentally determined digestible
      energy - 5.2 kJ/g digestible protein) and nutrients of eleven natural and five
      purified rat diets and compared the present results with the predicted values.
      Compared with natural diets, digestibility of gross energy (GE) and nutrients was
      higher by about 20 % in the purified diets (P < 0.0001). Mean GE digestibility in
      natural diets amounted to 71.4 % (range 53.3-83.5 %; n 11). Atwater factors
      predicted ME with satisfactory accuracy in purified diets. In contrast, for
      natural diets, only the equation for pig feed gave acceptable estimates of ME.
      Choosing an inappropriate predictive equation for ME resulted in considerable
      error. For prediction of ME in mixed rat feed, we propose to use the equation for
      pig feed for natural diets and Atwater factors for purified diets. If the
      equation for pig feed cannot be applied we suggest using the lower modified
      Atwater factors instead of the 'original' Atwater factors to estimate the ME of a
      diet.

PMID- 20047702
TI  - The effect of referral for brief intervention for alcohol misuse on repetition of
      deliberate self-harm: an exploratory randomized controlled trial.
AB  - BACKGROUND: Referral for brief intervention among people who misuse alcohol is
      reported to be effective but its impact among those who present to services
      following deliberate self-harm (DSH) has not been examined. METHOD: Consecutive
      patients who presented to an Emergency Department (ED) following an episode of
      DSH were screened for alcohol misuse. Those found to be misusing alcohol were
      randomly assigned to brief intervention plus a health information leaflet or to a
      health information leaflet alone. The primary outcome was whether the patient
      reattended an ED following a further episode of DSH during the subsequent 6
      months. Secondary outcomes were alcohol consumption, mental health and
      satisfaction with care measured 3 and 6 months after randomization. RESULTS: One
      hundred and three people took part in the study. Follow-up data on our primary
      outcome were obtained for all subjects and on 63% for secondary outcomes. Half
      those referred for brief intervention received it. Repetition of DSH was strongly
      associated with baseline alcohol consumption, but not influenced by treatment
      allocation. There was a non-significant trend towards the number of units of
      alcohol consumed per drinking day being lower among those randomized to brief
      intervention. CONCLUSIONS: Referral for brief intervention for alcohol misuse
      following an episode of DSH may not influence the likelihood of repetition of
      self-harm. Longer-term interventions may be needed to help people who
      deliberately harm themselves and have evidence of concurrent alcohol misuse.

PMID- 20047703
TI  - Cognitive functioning in chronic fatigue syndrome: a meta-analysis.
AB  - BACKGROUND: Cognitive problems are commonly reported in persons with chronic
      fatigue syndrome (CFS) and are one of the most disabling symptoms of this
      condition. A number of cognitive deficits have been identified, although the
      findings are inconsistent and hindered by methodological differences. The current
      study therefore conducted a meta-analysis of research examining cognitive
      functioning in persons with CFS in order to identify the pattern and magnitude of
      any deficits that are associated with this condition. METHOD: A comprehensive
      search of the PubMed and PsycINFO databases for studies that examined cognitive
      functioning in CFS between 1988 and 2008 identified 50 eligible studies. Weighted
      Cohen's d effect sizes, 95% confidence intervals and fail-safe Ns were calculated
      for each cognitive score. RESULTS: Evidence of cognitive deficits in persons with
      CFS was found primarily in the domains of attention, memory and reaction time.
      Deficits were not apparent on tests of fine motor speed, vocabulary, reasoning
      and global functioning. CONCLUSIONS: Persons with CFS demonstrate moderate to
      large impairments in simple and complex information processing speed and in tasks
      requiring working memory over a sustained period of time.

PMID- 20047704
TI  - Cognitive reappraisal modulates performance following negative feedback in
      patients with major depressive disorder.
AB  - BACKGROUND: Depressed patients show impaired performance following negative
      feedback; the probability of committing an error is increased immediately after
      an error. This deficit is assumed to be highly specific and to represent a trait
      marker of major depressive disorder (MDD). Inconsistencies in currently available
      data could reflect inter-individually different strategies to regulate negative
      affect. The present study examined modulation of performance following negative
      feedback by cognitive reappraisal to regulate aversive affect in depressed
      patients. METHOD: Thirty-three depressed patients and 33 control subjects
      performed tasks of varying difficulty over a prolonged time. Emotional feedback
      was given immediately after each trial. Performance was further analysed within
      subgroups using cognitive reappraisal of aversive events with high and low
      frequency. RESULTS: A significant group by task difficulty interaction for
      absolute number of subsequent errors revealed that depressed patients were
      especially impaired when receiving negative feedback more frequently. An
      increased probability of subsequent errors was shown in patients irrespective of
      task difficulty. Analysis of subgroups revealed higher absolute number and
      probability of subsequent errors only in depressed patients habitually not using
      cognitive reappraisal to regulate aversive emotions. Depressed patients using
      this strategy did not differ from controls. CONCLUSIONS: The present results
      replicate the observation of impaired performance in depressed patients following
      failure feedback. Most importantly, a subgroup of patients who habitually rely on
      cognitive reappraisal of aversion-eliciting events, such as negative performance
      feedback, was not impaired. This modulatory influence of emotion regulation
      strategies on performance subsequent to negative feedback suggests that training
      emotion regulation in achievement situations should be incorporated in current
      concepts to prevent relapse.

PMID- 20047705
TI  - Delivery outcome after maternal use of antidepressant drugs in pregnancy: an
      update using Swedish data.
AB  - BACKGROUND: Concerns have been expressed about possible adverse effects of the
      use of antidepressant medication during pregnancy, including risk for neonatal
      pathology and the presence of congenital malformations. METHOD: Data from the
      Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to
      identify women who reported the use of antidepressants in early pregnancy or were
      prescribed antidepressants during pregnancy by antenatal care: a total of 14 821
      women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses,
      infant neonatal diagnoses and the presence of congenital malformations were
      compared with all other women who gave birth, using the Mantel-Haenszel technique
      and with adjustments for certain characteristics. RESULTS: There was an
      association between antidepressant treatment and pre-existing diabetes and
      chronic hypertension but also with many pregnancy complications. Rates of induced
      delivery and caesarean section were increased. The preterm birth rate was
      increased but not that of intrauterine growth retardation. Neonatal complications
      were common, notably after tricyclic antidepressant (TCA) use. An increased risk
      of persistent pulmonary hypertension of the newborn (PPHN) was verified. The
      congenital malformation rate was increased after TCAs. An association between use
      of paroxetine and congenital heart defects was verified and a similar effect on
      hypospadias was seen. CONCLUSIONS: Women using antidepressants during pregnancy
      and their newborns have increased pathology. It is not clear how much of this is
      due to drug use or underlying pathology. Use of TCAs was found to carry a higher
      risk than other antidepressants and paroxetine seems to be associated with a
      specific teratogenic property.

PMID- 20047706
TI  - How should DSM-V classify eating disorder not otherwise specified (EDNOS)
      presentations in women with lifetime anorexia or bulimia nervosa?
AB  - OBJECTIVE: Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by
      longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify
      eating disorder (ED) presentations in individuals who no longer meet full
      criteria for these disorders. To consider this issue, we examined subthreshold
      presentations in women with initial diagnoses of AN and BN. METHOD: A total of
      246 women with AN or BN were followed for a median of 9 years; weekly symptom
      data were collected at frequent intervals using the Longitudinal Interval Follow
      up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations
      that were subthreshold for 3 months, including those narrowly missing full
      criteria for AN or BN, along with binge eating disorder (BED) and purging
      disorder. RESULTS: During follow-up, most women (77.6%) experienced a
      subthreshold presentation. Subthreshold presentation was related to intake
      diagnosis (Wald chi2=8.065, df=2, p=0.018). Individuals with AN most often
      developed subthreshold presentations resembling AN; those with BN were more
      likely to develop subthreshold BN. Purging disorder was experienced by half of
      those with BN and one-quarter of those with AN binge/purge type (ANBP); BED
      occurred in 20% with BN. Transition from AN or BN to most subthreshold types was
      associated with improved psychosocial functioning (p<0.001). CONCLUSIONS:
      Subthreshold presentations in women with lifetime AN and BN were common,
      resembled the initial diagnosis, and were associated with modest improvements in
      psychosocial functioning. For most with lifetime AN and BN, subthreshold
      presentations seem to represent part of the course of illness and to fit within
      the original AN or BN diagnosis.

PMID- 20047707
TI  - How does cognitive behaviour therapy reduce fatigue in patients with chronic
      fatigue syndrome? The role of physical activity.
AB  - BACKGROUND: Cognitive behaviour therapy (CBT) is known to reduce fatigue severity
      in chronic fatigue syndrome (CFS). How this change in symptomatology is
      accomplished is not yet understood. The purpose of the present study was to
      determine whether the effect of CBT on fatigue is mediated by an increase in
      physical activity. METHOD: Three randomized controlled trials were reanalysed,
      previously conducted to evaluate the efficacy of CBT for CFS. In all samples,
      actigraphy was used to assess the level of physical activity prior and subsequent
      to treatment or a control group period. The mediation hypothesis was analysed
      according to guidelines of Baron & Kenny [Journal of Personality and Social
      Psychology (1986)51, 1173-1182]. A non-parametric bootstrap approach was used to
      test statistical significance of the mediation effect. RESULTS: Although CBT
      effectively reduced fatigue, it did not change the level of physical activity.
      Furthermore, changes in physical activity were not related to changes in fatigue.
      Across the samples, the mean mediation effect of physical activity averaged about
      1% of the total treatment effect. This effect did not yield significance in any
      of the samples. CONCLUSIONS: The effect of CBT on fatigue in CFS is not mediated
      by a persistent increase in physical activity.

PMID- 20047708
TI  - Attributions for hallucinations in bipolar affective disorder.
AB  - BACKGROUND: Attributions for hallucinations in the "schizophrenia" spectrum
      disorders have been subject to extensive investigation; however, in comparison
      very little is known about attributions for hallucinations in the bipolar
      disorders spectrum. AIMS: This preliminary study is an attempt to investigate
      attributions for hallucinations in bipolar disorder with regard to prevalence,
      modality and mood state. METHOD: Forty participants were recruited from a larger
      randomized control trial into CBT for bipolar disorder and asked to provide
      information related to attributions for hallucinations both in and out of
      episode. Data was collected using a specially designed instrument based on the
      Belief about Voices Questionnaire (BAVQ). RESULTS: Just under half of the
      participants reported experiencing true hallucinations during their illness.
      Participants tended to report visual hallucinations in mania and auditory
      hallucinations in depression. The vast majority of participants attributed
      hallucinations to illness when out of episode, and unlike in previously reported
      analyses of attributions for hallucinations in the schizophrenia spectrum,
      malevolent/omnipotent attributions were comparatively rare. CONCLUSIONS:
      Attributions for hallucinations in bipolar disorder may be clinically distinct
      from attributions previously observed in the schizophrenia spectrum, and CBT
      aimed at reducing the distress associated with these attributions may have to be
      tailored accordingly.

PMID- 20047710
TI  - Smoking behaviour is associated with expression and phosphorylation of CREB in
      human buffy coat.
AB  - Nicotine induces various acute und chronic pharmacological effects which can be
      long lasting and might lead to nicotine dependence. Nicotinic acetylcholine
      receptors (nAChRs) are involved in nicotine-induced phosphorylation of CREB
      (cyclic AMP response element-binding protein) in PC12h cells. Several studies,
      mainly done in animal models, report that CREB plays a role in anxiety, memory
      and substance abuse as well as in affective disorders. Information regarding
      nicotine effects on gene expression in humans in vivo is rare. The aim of our
      study was to determine whether or not there are differences between smokers and
      non-smoking controls in terms of CREB expression and phosphorylation in human
      buffy coat. Comparing 32 smokers with 76 non-smoking controls we found
      significantly elevated relative (p=0.043) and absolute (p=0.040) CREB
      phosphorylation in the blood of smokers who had smoked two cigarettes in the past
      6 h. In contrast, the score of the State and Trait Anxiety Inventory, total-CREB
      and mRNA-CREB were not significantly different. Multiple regression analysis
      revealed a significant relation between the number of cigarettes smoked daily
      (R2=0.143, p=0.023), the Fagerstrom Test for Nicotine Dependence score (R2=0.145,
      p=0.022) and the expression of CREB. Moreover, in accord with previously
      published data our analysis suggests gender and age as factors that significantly
      influence expression and phosphorylation of CREB. It appears that human buffy
      coat is suitable for studying pharmacological effects of substances such as
      nicotine on selected signal transduction pathways in humans in vivo. This kind of
      study may be helpful for translating findings from animal models and cell
      cultures.

PMID- 20047709
TI  - Genetic variation in HTR2A influences serotonin transporter binding potential as
      measured using PET and [11C]DASB.
AB  - In a previous study we showed that genetic variation in HTR2A, which encodes the
      serotonin 2A receptor, influenced outcome of citalopram treatment in patients
      with major depressive disorder. Since chronic administration of citalopram, which
      selectively and potently inhibits the serotonin transporter (5-HTT), putatively
      enhances serotonergic transmission, it is conceivable that genetic variation
      within HTR2A also influences pretreatment 5-HTT function or serotonergic
      transmission. The present study used positron emission tomography (PET) and the
      selective 5-HTT ligand, [11C]DASB, to investigate whether the HTR2A marker
      alleles that predict treatment outcome also predict differences in 5-HTT binding.
      Brain levels of 5-HTT were assessed in vivo using PET measures of the non
      displaceable component of the [11C]DASB binding potential (BPND). DNA from 43
      patients and healthy volunteers, all unmedicated, was genotyped with 14 single
      nucleotide polymorphisms located within or around HTR2A. Allelic association with
      BPND was assessed in eight brain regions, with covariates to control for race and
      ethnicity. We detected allelic association between [11C]DASB BPND in thalamus and
      three markers in a region spanning the 3' untranslated region and second intron
      of HTR2A (rs7333412, p=0.000045; rs7997012, p=0.000086; rs977003, p=0.000069).
      The association signal at rs7333412 remained significant (p<0.05) after applying
      corrections for multiple testing via permutation. Genetic variation in HTR2A that
      was previously associated with citalopram treatment outcome was also associated
      with thalamic 5-HTT binding. While further work is needed to identify the actual
      functional genetic variants involved, these results suggest that a relationship
      exists between genetic variation in HTR2A and either 5-HTT expression or central
      serotonergic transmission that influences the therapeutic response to 5-HTT
      inhibition in major depression.

PMID- 20047711
TI  - Preclinical characterization of BRL 44408: antidepressant- and analgesic-like
      activity through selective alpha2A-adrenoceptor antagonism.
AB  - Biogenic amines such as norepinephrine, dopamine, and serotonin play a well
      described role in the treatment of mood disorders and some types of pain. As
      alpha2A-adrenoceptors regulate the release of these neurotransmitters, we
      examined the therapeutic potential of BRL 44408, a potent (Ki=8.5 nM) and
      selective (>50-fold) alpha2A-adrenoceptor antagonist (K(B)=7.9 nM). In rats, BRL
      44408 penetrated the central nervous system resulting in peak brain and plasma
      concentrations of 586 ng/g and 1124 ng/ml, respectively. In a pharmacodynamic
      assay, pretreatment with BRL 44408 to rats responding under a fixed-ratio 30
      operant response paradigm resulted in a rightward shift of the clonidine dose
      response curve, an effect indicative of alpha2-adrenoceptor antagonism in vivo.
      Consistent with presynaptic autoreceptor antagonism and tonic regulation of
      neurotransmitter release, acute administration of BRL 44408 elevated
      extracellular concentrations of norepinephrine and dopamine, but not serotonin,
      in the medial prefrontal cortex. Additionally, BRL 44408, probably by inhibiting
      alpha2A heteroceptors, produced a significant increase in cortical levels of
      acetylcholine. In the forced swim test and schedule-induced polydipsia assay, BRL
      44408 produced an antidepressant-like response by dose-dependently decreasing
      immobility time and adjunctive water intake, respectively, while in a model of
      visceral pain, BRL 44408 exhibited analgesic activity by decreasing para
      phenylquinone (PPQ)-induced abdominal stretching. Finally, BRL 44408 did not
      produce deficits in overall motor coordination nor alter general locomotor
      activity. This preclinical characterization of the neurochemical and behavioural
      profile of BRL 44408 suggests that selective antagonism of alpha2A-adrenoceptors
      may represent an effective treatment strategy for mood disorders and visceral
      pain.

PMID- 20047712
TI  - Oxazepam and temazepam attenuate paroxetine-induced elevation of serotonin levels
      in guinea-pig hippocampus.
AB  - Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are used as a first-line
      treatment in depression. However, many depressed patients are also treated with
      benzodiazepines to alleviate increased anxiety and sleep disturbances normally
      associated with depression. Since benzodiazepines inhibit 5-HT neuronal firing
      activity, they might attenuate SSRI-induced increase in extracellular 5-HT
      levels. This study aimed to assess, using in-vivo microdialysis, the effects of
      the benzodiazepines oxazepam or temazepan on the SSRI paroxetine-induced 5-HT
      increase in the hippocampus of freely moving guinea-pigs. It was found that the
      acute systemic administration of paroxetine increased extracellular 5-HT levels.
      Pre-administration of oxazepam or temazepam significantly diminished the
      paroxetine-induced elevation of extracellular 5-HT levels (from 350% to 200% of
      baseline). It was concluded that benzodiazepines attenuate the ability of SSRIs
      to elevate hippocampal 5-HT levels. Thus, co-administration of benzodiazepines
      might affect the therapeutic efficacy of SSRI treatment.

PMID- 20047713
TI  - Converging action of alcohol consumption and cannabinoid receptor activation on
      adult hippocampal neurogenesis.
AB  - Alcoholism is characterized by successive periods of abstinence and relapse,
      resulting from long-lasting changes in various circuits of the central nervous
      system. Accumulating evidence points to the endocannabinoid system as one of the
      most relevant biochemical systems mediating alcohol addiction. The
      endocannabinoid system regulates adult neurogenesis, a form of long-lasting adult
      plasticity that occurs in a few areas of the brain, including the dentate gyrus.
      Because exposure to psychotropic drugs regulates adult neurogenesis, it is
      possible that neurogenesis might be implicated in the pathophysiology, and hence
      treatment, of neurobiological illnesses related to drugs of abuse. Here, we
      investigated the sensitivity of adult hippocampal neurogenesis to alcohol and the
      cannabinoid receptor agonist WIN 55,212-2 (WIN). Specifically, we analysed the
      potential link between alcohol relapse, cannabinoid receptor activation, and
      adult neurogenesis. Adult rats were exposed to subchronic alcohol binge
      intoxication and received the cannabinoid receptor agonist WIN. Another group of
      rats were subjected to an alcohol operant self-administration task. Half of these
      latter animals had continuous access to alcohol, while the other half were
      subjected to alcohol deprivation, with or without WIN administration. WIN
      treatment, when administered during alcohol deprivation, resulted in the greatest
      increase in alcohol consumption during relapse. Together, forced alcohol binge
      intoxication and WIN administration dramatically reduced hippocampal
      neurogenesis. Furthermore, adult neurogenesis inversely correlated with voluntary
      consumption of alcohol. These findings suggest that adult hippocampal
      neurogenesis is a key factor involved in drug abuse and that it may provide a new
      strategy for the treatment of alcohol addiction and dependence.

PMID- 20047714
TI  - Panicolytic-like effect of BDNF in the rat dorsal periaqueductal grey matter: the
      role of 5-HT and GABA.
AB  - A wealth of evidence suggests a role for brain-derived neurotrophic factor (BDNF)
      and its receptor tropomyosin-related kinase B (TrkB) in the aetiology of
      depression and in the mode of action of antidepressant drugs. Less clear is the
      involvement of this neurotrophin in other stress-related pathologies such as
      anxiety disorders. The dorsal periaqueductal grey matter (DPAG), a midbrain area
      rich in BDNF and TrkB receptor mRNAs and proteins, has been considered a key
      structure in the pathophysiology of panic disorder. In this study we investigated
      the effect of intra-DPAG injection of BDNF in a proposed animal model of panic:
      the escape response evoked by the electrical stimulation of the same midbrain
      area. To this end, the intensity of electrical current that needed to be applied
      to DPAG to evoke escape behaviour was measured before and after microinjection of
      BDNF. We also assessed whether 5-HT- or GABA-related mechanisms may account for
      the putative behavioural/autonomic effects of the neurotrophin. BDNF (0.05, 0.1,
      0.2 ng) dose-dependently inhibited escape performance, suggesting a panicolytic
      like effect. Local microinjection of K252a, an antagonist of TrkB receptors, or
      bicuculline, a GABAA receptor antagonist, blocked this effect. Intra-DPAG
      administration of WAY-100635 or ketanserin, respectively 5-HT1A and 5-HT2A/2C
      receptor antagonists, did not alter BDNF's effects on escape. Bicuculline also
      blocked the inhibitory effect of BDNF on mean arterial pressure increase caused
      by electrical stimulation of DPAG. Therefore, in the DPAG, BDNF-TrkB signalling
      interacts with the GABAergic system to cause a panicolytic-like effect.

PMID- 20047715
TI  - Efficacy of the atypical antipsychotic aripiprazole in d-amphetamine-based
      preclinical models of mania.
AB  - The atypical antipsychotic aripiprazole has been demonstrated to reduce symptoms
      of bipolar mania. To further profile the antimanic-like properties of
      aripiprazole in relevant preclinical models, we examined its efficacy in d
      amphetamine-based behavioural models of acute mania in rats. The effects of acute
      and repeated administration of aripiprazole were assessed in the facilitation of
      intracranial self-stimulation (ICSS) and hyperlocomotion after acute d
      amphetamine, and in the sensitized facilitation of ICSS function and
      hyperlocomotion after repeated d-amphetamine. Acutely, aripiprazole (0.75, 1.5
      and 2.5 mg/kg i.p.) increased ICSS thresholds, attenuated the reward-facilitating
      effects of d-amphetamine (0.5 mg/kg i.p.), decreased motor activity and prevented
      d-amphetamine-induced hyperlocomotion. Co-administration of aripiprazole and d
      amphetamine for 7 d resulted in aripiprazole counteracting the d-amphetamine
      induced sensitization in facilitation of brain reward function and
      hyperlocomotion. These results indicate the efficacy of aripiprazole in d
      amphetamine-based preclinical models of acute mania that are characterized by
      increased motivational drive and/or hyperfunction of brain reward.

PMID- 20047717
TI  - Recent advances in psychopathy research.

PMID- 20047716
TI  - DNA sequence variants of the FKBP5 gene are associated with unipolar depression.
AB  - FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and,
      therefore, is suggested to play a role in the regulation of the hypothalamic
      pituitary-adrenocortical system and the pathophysiology of depression.
      Previously, three studies identified single nucleotide polymorphisms (SNPs) in
      the FKBP5 gene associated with response to antidepressants, and one study found
      an association with diagnosis of depression. We selected five markers from the
      region of interest. A case-control sample comprising 268 German in-patients with
      recurrent unipolar depression, and 284 German controls recruited from the general
      population were available. Association of the selected FKBP5 sequence variants
      with clinical depression were analysed. In addition, we explored association with
      treatment response by (a) the Hamilton Depression Rating Scale and (b) the
      dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test, as well as
      association with hippocampal volumes in a subpopulation of 110 patients. For
      three of the five investigated SNPs we were able to show association with the
      diagnosis of depression. In the subpopulation of 110 patients, diagnosis-related
      alleles were also associated with the reduction of cortisol secretion in the
      Dex/CRH test during a 4-wk treatment period, while psychopathological changes
      were not associated. Furthermore, diagnosis-related alleles were associated with
      reduction of the hippocampal volume. This study extends the replicated
      association of a promoter SNP with antidepressant response on a biological level
      by demonstrating normalization of the cortisol response under Dex/CRH stimulation
      during treatment. Furthermore, several of the investigated SNPs were associated
      with the disease status and the intermediate phenotype of hippocampal volume.

PMID- 20047718
TI  - Psychopathy: assessment and forensic implications.
AB  - Psychopathy is commonly viewed as a personality disorder defined by a cluster of
      interpersonal, affective, lifestyle, and antisocial traits and behaviours,
      including grandiosity, egocentricity, deceptiveness, shallow emotions, lack of
      empathy or remorse, irresponsibility, impulsivity, and a tendency to violate
      social norms. In our article, we outline standard methods for the assessment of
      psychopathy, its association with antisocial personality disorder (ASPD), and its
      implications for clinical and forensic issues, including crime and violence, risk
      assessment, and treatment options.

PMID- 20047719
TI  - Extending the construct of psychopathy to youth: implications for understanding,
      diagnosing, and treating antisocial children and adolescents.
AB  - This paper reviews several attempts to extend the construct of psychopathy to
      children and adolescents. The research suggests that the presence of callous
      unemotional (CU) traits may be particularly important. Specifically, the presence
      of these traits designates a clinically important subgroup of youth with
      childhood-onset conduct problems who show a particularly severe, aggressive, and
      stable pattern of antisocial behaviour. Also, children with CU traits show
      numerous emotional, cognitive, and personality features that are distinct from
      other antisocial youth that are similar to features found in adults with
      psychopathy. The research on CU traits has important implications for
      understanding the different causal pathways through which children develop severe
      antisocial and aggressive behaviour, as well as implications for diagnosing and
      intervening with antisocial youth.

PMID- 20047720
TI  - The neurobiology of psychopathy: a neurodevelopmental perspective.
AB  - We provide an overview of the neurobiological underpinnings of psychopathy.
      Cognitive and affective-emotional processing deficits are associated with
      abnormal brain structure and function, particularly the amygdala and
      orbitofrontal cortex. There is limited evidence of lower cortisol levels being
      associated with psychopathic personality. Initial developmental research is
      beginning to suggest that these neurobiological processes may have their origins
      early in life. Findings suggest that psychopathic personality may, in part, have
      a neurodevelopmental basis. Future longitudinal studies delineating
      neurobiological correlates of the analogues of interpersonal-affective and
      antisocial features of psychopathy in children are needed to further substantiate
      a neurodevelopmental hypothesis of psychopathy.

PMID- 20047721
TI  - Incidence and course of suicidal ideation and suicide attempts in the general
      population.
AB  - OBJECTIVE: Suicidal ideation and suicide attempts are important indicators of
      extreme emotional distress. However, little is known about predictors of onset
      and course of suicidality in the general population. Our study tried to fill this
      gap by analyzing data from a prospectively followed community sample. METHOD:
      Data were derived from the Netherlands Mental Health Survey and Incidence Study
      (NEMESIS), a 3-wave cohort study in a representative sample (n = 4848) of the
      Dutch adult general population. RESULTS: The 3-year incidence of suicidal
      ideation and suicide attempts was 2.7% and 0.9%, respectively. Predictors of
      first-onset suicidal ideation and suicide attempts were sociodemographic
      variables (especially the negative change in situation variables), life events,
      personal vulnerability indicators, and emotional (mood and anxiety) disorders.
      Comparison of the corresponding odds ratios and confidence intervals revealed
      that predictors for first-onset suicidal ideation and suicide attempts did not
      differ significantly. One of the strongest predictors of incident suicide
      attempts was previous suicidal ideation. Regarding the course of suicidal
      ideation, it was found that 31.3% still endorsed these thoughts and 7.4% reported
      having made a suicide attempt 2 years later. CONCLUSIONS: Similar predictors were
      found for first-onset suicidal ideation and suicide attempts. This suggests that
      suicidal behaviours may be ordered on a continuum and have shared risk factors.
      While suicidal thoughts may be necessary for, they are not sufficient predictors
      of, suicidal acts. The course of suicidality in the general population can be
      characterized by a minority of people having suicidal experiences that develop
      over time with progressively increasing severity.

PMID- 20047722
TI  - Traditional postpartum practices and rituals: clinical implications.
AB  - OBJECTIVES: In many cultures, postpartum rituals are observed because they are
      believed to have beneficial mental health effects. Our systematic review examines
      the research literature investigating the effects of postpartum rituals on
      postpartum depression (PPD) to determine if the rituals protect against PPD.
      METHODS: MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Library were
      searched (from 1966 to October 31, 2008). Reference lists of relevant articles
      and links to related articles were also examined. Both qualitative and
      quantitative studies that focused on traditional practices and rituals in the
      postpartum period (that is, within the first year following childbirth) and their
      relation to PPD or mood were included. RESULTS: Seventy-two studies were
      considered, with 12 meeting the inclusion criteria. The data were summarized
      according to the type of ritual including: organized support, diet, and other or
      multiple postpartum practices, and evidence for or against a protective effect on
      PPD. Although limited, not all studies suggested that the rituals prevent PPD.
      Overall, there is some evidence that postpartum rituals dictating appropriate and
      wanted social support may be of some protective value, depending on numerous
      contextual factors. CONCLUSIONS: This area needs more culturally sensitive and
      systematic research. Current studies suggest that the key protective element may
      be the presence of welcome support rather than the specific ritual.

PMID- 20047723
TI  - Prospective evaluation of the effect of major depression on working status in a
      population sample.
AB  - OBJECTIVE: Numerous surveys have reported associations between major depressive
      episodes (MDEs) and occupational status, but cross-sectional studies cannot
      quantify the risks of employment transitions nor clarify their temporal
      direction. The goal of our study was to estimate the impact of MDE on subsequent
      employment status in a longitudinal community cohort. METHODS: Data from the
      National Population Health Survey (NPHS) were used. Proportional hazard models
      and logistic regression were employed to evaluate the effect of MDE on working
      status during the 1994 to 2004 interval among respondents who reported working at
      a job or business at baseline. RESULTS: MDE was associated with an increased risk
      of movement to nonworking status. People aged 26 to 45 years with MDEs have more
      than double the risk of this transition (HR = 2.6; 95% CI 1.8 to 3.6, P < 0.001).
      The probability of transition to nonworking status was higher, but the relative
      effect was smaller in people aged 46 to 65 years (HR = 1.2; 95% CI 0.7 to 2.0, P
      = 0.47). Retirement or perceived lack of availability of work did not contribute
      to the association. CONCLUSIONS: MDE is associated with an elevated risk of
      transition from working to nonworking status, especially in people aged 26 to 45
      years.

PMID- 20047724
TI  - Psychological treatment of obsessive-compulsive disorder in patients with major
      depression: a pilot randomized controlled trial.
AB  - OBJECTIVE: To examine the efficacy of cognitive-behavioural therapy (CBT) for
      obsessive-compulsive disorder (OCD) in patients with comorbid major depressive
      disorder (MDD). METHOD: Participants (n = 29) diagnosed with comorbid OCD and MDD
      were randomized to receive standard CBT for OCD or integrated CBT that included
      an exclusive focus on treating MDD in the first phase of treatment and OCD in the
      second phase of treatment. RESULTS: Both treatments resulted in statistically
      significant improvements in OCD and MDD symptoms. Treatment effects and recovery
      rates in the intent-to-treat sample were lower in both treatments, compared with
      past studies that excluded patients with MDD. However, among treatment
      completers, both treatments resulted in statistically significant and clinically
      meaningful improvements in OCD and MDD symptoms. CONCLUSIONS: CBT holds promise
      as an efficacious treatment for people with comorbid OCD and MDD. The high
      treatment dropout rate with comorbid patients suggests that additional treatment
      strategies are required to enhance retention and optimize clinical outcomes.

PMID- 20047725
TI  - Suppression of keratin 18 gene expression in bovine blastocysts by RNA
      interference.
AB  - The expression of the cytoskeleton protein Keratin 18 (KRT18) starts at the onset
      of bovine blastocyst formation. KRT18 is solely expressed in the trophectoderm
      and can therefore be used as a marker for trophectodermal differentiation. In the
      present study, the expression of KRT18 was suppressed by RNA interference to
      probe its functional importance in bovine blastocyst formation. Microinjection of
      KRT18 double-stranded RNA into the cytoplasm of zygotes resulted in reduced KRT18
      mRNA (76% reduction) and protein expression at the blastocyst stage and a lower
      developmental competence (41% reduction in the percentage of blastocyst
      formation) compared with non-injected and phosphate-buffered saline (PBS)
      injected controls. KRT18 downregulation was associated with reduced mRNA
      expression of KRT8, the binding partner of KRT18, but had no effect on the
      expression of KRT19, CDH1 and DSP, other genes involved in intermediate filament
      and cytoskeleton formation. The results of the present study demonstrated that
      KRT18 knockdown in preimplantation embryos results in reduced blastocyst
      formation, but no further morphological aberrations were observed with regard to
      the biological function of KRT18. These observations could be due to the function
      of KRT18 being replaced by that of another gene, the surviving blastocysts
      expressing the minimum level of KRT18 required for normal blastocyst development
      or the possibility that further aberrations may occur later in development.

PMID- 20047726
TI  - Transmission electron microscopy (TEM) of equine conceptuses at 14 and 16 days of
      gestation.
AB  - The present study gives a detailed ultrastructural description of equine
      conceptuses at Day 14 (n = 2) and Day 16 (n = 3) after ovulation. Whereas on Day
      14 only primitive structures were seen, on Day 16 neurulation and formation of
      mesodermal somites had taken place. The ectoderm of the embryo itself and the
      surrounding trophoblast ectodermal cells were characterised by specific cell
      surface differentiations. At the embryonic ectodermal cell surface (14 and 16
      days) remarkable protruded and fused cytoplasmic projections were seen, typically
      associated with macropinocytotic events involved in macromolecule and fluid
      uptake. This finding adds an important point to the expansion mode of the
      hypotone equine conceptus, which is characterised by 'uphill' fluid uptake.
      Numerous microvilli and coated endocytotic pits at the apical trophoblast
      membrane emphasised its absorptive character. Endodermal cells were arranged
      loosely with only apically located cellular junctions leaving large intercellular
      compartments. At the border of the embryonic disc apoptotic cells were regularly
      observed indicating high remodelling activities in this area. Conspicuous blister
      like structures between ectoderm and mesoderm were seen in the trilaminar part of
      Day-14 and -16 conceptuses. These were strictly circumscribed despite not being
      sealed by cellular junctions between germinal layers. It is possible that these
      blisters are involved in embryo positioning; however, further studies are needed
      to verify this.

PMID- 20047727
TI  - Effects on differentiation of reproductive organs and sexual behaviour in
      Japanese quail by excessive embryonic ERalpha activation.
AB  - Exposure of Japanese quail (Coturnix japonica) embryos to oestrogenic substances
      disrupts sexual differentiation of the reproductive tract of both sexes and
      impairs the copulatory behaviour of the adult male. To examine whether these
      effects can be induced by selective activation of oestrogen receptor alpha
      (ERalpha), Japanese quail eggs were injected with various doses of the selective
      ERalpha agonist 16alpha-lactone-oestradiol (16alpha-LE(2)). The natural oestrogen
      17beta-oestradiol (E(2)) was used as a positive control. Both 16alpha-LE(2) and
      E(2) induced formation of an ovary-like cortex in the left testis (ovotestis) and
      reduced the size of the right testis in male embryos. The asymmetry in testis
      size remained in sexually mature males. Both substances induced retention and
      malformation of the Mullerian ducts in embryos of both sexes and malformed
      oviducts in juveniles. Male copulatory behaviour was suppressed by embryonic
      exposure to E(2) and the highest dose of 16alpha-LE(2). However, the lower dose
      of 16alpha-LE(2), which markedly affected development of the reproductive organs,
      was without effects on behaviour. It can therefore not be excluded that the
      behavioural demasculinisation at the 100-fold higher dose involved cross
      activation of oestrogen receptor beta (ERbeta). In conclusion, our results
      suggest that oestrogen-induced disruption of reproductive organ development in
      Japanese quail can be mediated via ERalpha, whereas the role of ERalpha in
      demasculinisation of copulatory behaviour remains to be clarified.

PMID- 20047728
TI  - Developmental kinetics and gene expression in male and female bovine embryos
      produced in vitro with sex-sorted spermatozoa.
AB  - Using bovine embryos generated in vitro from IVF with X-sorted, Y-sorted and
      unsorted spermatozoa, we compared the kinetics of male and female embryo
      development and gene expression between male and female blastocysts. Bovine in
      vitro-matured oocytes (n = 8858) were fertilised with spermatozoa from each of
      three different bulls (X-sorted, Y-sorted or unsorted spermatozoa depending on
      the experiment). The cleavage rate was assessed 24, 27, 30, 33, 36, 40, 44 and 48
      h post insemination (h.p.i.) and blastocyst development was recorded on Days 6-9.
      The relative mRNA abundance of nine genes (GSTM3, DNTM3A, PGRMC1, TP53, BAX,
      COX2, IGF2R, AKR1B1 and PLAC8) was analysed in male and female Day 7 blastocysts
      produced with sorted and unsorted spermatozoa from one bull. Cumulative cleavage
      rate and blastocyst yield were significantly higher in the unsorted group
      compared with the X- or Y-sorted group from the same bull (P < or = 0.05).
      Although differences existed between bulls in terms of cleavage rate, no
      differences were observed in cleavage rate between X- and Y-sorted spermatozoa
      within a bull. The blastocyst yield was significantly higher only for Bull 3 when
      the Y-sorted spermatozoa were used (27.1+2.8 v. 19.1+1.4 for Y- and X-sorted
      spermatozoa, respectively; P < 0.05). There were no differences in the mRNA
      abundance of the nine genes analysed between embryos of the same sex produced
      with sorted or unsorted spermatozoa. However, significant differences in polyA
      mRNA abundance were observed between male and female blastocysts for three genes
      (GSTM3, DNMT3A and PGRMC1; P < or = 0.05). In conclusion, the use of sorted
      rather than unsorted spermatozoa in IVF significantly delays the onset of first
      cleavage. Differences were noted between bulls, but not between X- and Y-sorted
      spermatozoa, and although no differences were found in terms of the mRNA
      abundance of the nine genes tested between sorted and unsorted spermatozoa, sex
      related differences were found in the case of three genes.

PMID- 20047729
TI  - Iloprost, a prostacyclin analogue, stimulates meiotic maturation and early
      embryonic development in pigs.
AB  - Oviduct fluid contains various cytokines and growth factors that enhance the
      embryo development during the preimplantation period. In hatched embryos,
      prostacyclin (PGI(2)) improves implantation, but its role during oocyte
      maturation and early embryo development remains contentious. Therefore, in the
      present study, we examined the effects of a PGI(2) analogue (iloprost) on meiotic
      maturation and early embryonic development in pigs, as well on the structural
      integrity, mitochondrial membrane potential and apoptosis in blastocysts. First,
      meiotic maturation in pig oocytes was examined in the presence of increasing
      concentrations of iloprost (1, 5 and 10 muM). After IVM, a higher proportion of
      iloprost-treated compared with untreated oocytes was in MII (90.0% v. 65.7%,
      respectively; P < 0.05). In addition, protein kinase A activity increased in
      iloprost-treated oocytes, indicating increased intracellular cAMP concentrations.
      After 22 h iloprost treatment (44 h total incubation time), western blotting
      demonstrated increased expression of extracellular signal-regulated kinase (ERK)
      1/2, phosphorylated (p-) ERK1/2, cAMP response element-binding protein (CREB), p
      CREB and cyclo-oxygenase-2, indicating activation of the mitogen-activated
      protein kinase and PGI(2) pathways. In addition, the frequency of polyspermy
      decreased in iloprost-treated oocytes (19.9%) compared with control (35.8%),
      whereas the rate of blastocyst formation increased (P < 0.05). Terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) showed that
      the number of nuclei containing fragmented DNA at the blastocyst stage decreased
      in the iloprost-treated group compared with control (1.2% v. 3.6%, respectively).
      In conclusion, iloprost appears to play a direct role in porcine oocyte
      maturation by enhancing blastocyst structure and survival.

PMID- 20047730
TI  - Ultrasonographic characterisation of prenatal development in European brown hares
      (Lepus europaeus PALLAS, 1778): an evolutionary approach.
AB  - The European brown hare is one species in which reproduction appears to be
      particularly complex. Therefore, we studied the reproductive tract and prenatal
      development using high-resolution ultrasound of 159 pregnancies in 45 captive
      female hares. Consecutive examination of live hares was particularly useful in
      evaluating the very early stages of gestation. As such, it was possible to detect
      corpora lutea by Day 3 and embryonic vesicles, representing the earliest uterine
      embryonic stages, by Day 6. On Day 11, the heart beat of the embryo was
      detectable for the first time. We defined ultrasonographic milestones that were
      characteristic of the different stages of pregnancy. We also calculated growth
      models using eight different morphological parameters, including development of
      the corpus luteum. On the basis of these results, it is now possible to estimate
      the gestational age of a pregnant doe without knowing the date of conception. In
      contrast with the European rabbit, a distant relative, European hares give birth
      to precocial young. A comparison of the prenatal growth rate of both species
      suggests that the precocial state of the hare neonate is a more recently derived
      evolutionary characteristic, whereas the altricial condition of rabbits
      represents the ancestral mode.

PMID- 20047731
TI  - Chronic fetal and maternal instrumentation in pregnant sheep: effect on gestation
      length and birthweight.
AB  - The objective was to compare gestation length in chronically instrumented
      (laboratory) pregnant sheep (n = 131) and in the breeding flock (n = 476) that
      provided the experimental sheep. In the breeding flock, gestation length was
      normally distributed and varied between 141 and 151 days (mean = 147 +/- 0.1
      days). In the laboratory sheep, gestation length varied between 128 and 151 days
      (mean = 142 +/- 1 day), and was bimodal, with 35.9% delivering preterm (<141
      days). To examine potential factors that contributed to the preterm birth, a
      severity score was used, which comprised surgery characteristics, number of
      experiments and maternal or fetal complications. There was a significant inverse
      linear relationship (P < 0.001) between the total severity score and gestation
      length. The median values for the surgical (15 v. 12), overall complication (6 v.
      2), maternal complication (2 v. 0) and fetal complication (2 v. 2) components
      were significantly greater in the preterm compared with the term groups. There
      was no relationship between fetal number and gestation length in either group. It
      is concluded that in chronic pregnant sheep preparations, there is a significant
      incidence of preterm birth and that this is associated with the severity of the
      surgical intervention and with several maternal and fetal complications.

PMID- 20047732
TI  - Involvement of E-cadherin in early in vitro development of adult and juvenile
      sheep embryos.
AB  - The oocyte-to-embryo transition in mammals depends on maternal proteins and
      transcripts, which accumulate during oocyte differentiation. The aim of the
      present study was to examine the role of the junctional proteins beta-catenin and
      E-cadherin during preimplantation in vitro embryo development in sheep, comparing
      the competence of adult and prepubertal oocytes. We analysed the concentration of
      beta-catenin and E-cadherin in immature and in vitro-matured oocytes. There was a
      significant increase in E-cadherin concentration after 24 h of in vitro
      maturation and this was lower in prepubertal oocytes than in adult ones. We
      therefore studied the expression and distribution of E-cadherin during the major
      transition from maternal to embryonic genome. E-cadherin distribution and
      localisation in sheep was age- and developmental-stage dependent and was related
      to developmental kinetics. In fact, in adults, the majority of embryos showed the
      proper distribution of E-cadherin just beneath the membrane surfaces of all
      blastomeres and the percentage of embryos with this distribution increased with
      the increase in cell number during development. On the contrary, and regardless
      of their developmental stage, the majority of prepubertal embryos showed an
      uneven distribution of the protein, often associated with the occurrence of
      cellular fragmentation. In conclusion, our results suggest that E-cadherin plays
      a pivotal role during preimplantation embryo growth in sheep and may be one of
      the possible cytoplasmic factors involved in the reduced developmental competence
      of prepubertal female gametes.

PMID- 20047733
TI  - Spermatocyte apoptosis, which involves both intrinsic and extrinsic pathways,
      explains the sterility of Graomys griseoflavus x Graomys centralis male hybrids.
AB  - Spermatogenic impairment and the apoptotic pathways involved in establishing
      sterility of male hybrids obtained from crossing Graomys griseoflavus females
      with Graomys centralis males were studied. Testes from G. centralis, G.
      griseoflavus and hybrids were compared at different ages. Terminal transferase
      mediated dUTP nick-end labelling assay (TUNEL), Fas, Bax and cytochrome c
      labelling were used for apoptosis evaluation, and calbindin D(28k) staining as an
      anti-apoptotic molecule. In 1-month-old animals, spermatocytes were positive for
      all apoptotic markers, but moderate TUNEL (+) spermatocyte frequency was only
      found in G. centralis. At subsequent ages, the apoptotic markers were
      downregulated in testes from parental cytotypes, but not in hybrid testes. TUNEL
      (+) spermatocytes were present at 78% and 44% per tubule cross-section in 2- and
      3-month-old hybrid animals, respectively. Pachytene spermatocyte death in adult
      hybrids occurs via apoptosis, as revealed by high caspase-3 expression. Calbindin
      was highly expressed in spermatocytes of adult hybrids, in which massive cell
      death occurs via apoptosis. Calbindin co-localisation with TUNEL or Fas, Bax and
      cytochrome c was very limited, suggesting an inverse regulation of calbindin and
      apoptotic markers. Hybrid sterility is due to breakdown of spermatogenesis at the
      pachytene spermatocyte stage. Both extrinsic and intrinsic pathways are involved
      in apoptosis of spermatocytes, which are the most sensitive cell type to
      apoptotic stimuli.

PMID- 20047734
TI  - Reliability of ultrasound for early sexing of goat fetuses derived from natural
      mating and from fresh, frozen and vitrified embryo transfer.
AB  - The aim of the present study was to identify the migration period of the genital
      tubercle and its later differentiation into external genital structures in
      fetuses derived from natural mating and fetuses from fresh, frozen and vitrified
      embryo transfer. A transrectal ultrasound with a double-frequency linear
      transducer (6.0 and 8.0 MHz) was used to monitor 123 goat fetuses, which were
      allocated to one of four groups: fetuses originating from controlled natural
      mating (G1, n = 32) and fetuses derived from fresh (G2, n = 34), frozen (G3, n =
      30) and vitrified (G4, n = 27) embryo transfer. The transferable embryos were
      collected 7 days after mating by laparoscopy. Migration of the genital tubercle
      occurred significantly earlier (P < 0.05) in G1 than in G2, G3 and G4. The
      visualisation of the scrotum, prepuce and vulva occurred significantly earlier (P
      < 0.05) in G1 than in G2, G3 and G4. Our results show that fetal sexing is
      feasible after 55 days for fetuses from natural mating and after 60 days in
      fetuses from fresh and cryopreserved embryos. Thus, real-time ultrasonography is
      a reliable tool for fetal sex determination in goats after Day 50 of pregnancy,
      taking into account both the location of the genital tubercle and the
      identification of external genital structures.

PMID- 20047735
TI  - Energy minimum theorem based on AGA, Lyapunov and force field for CADD
      techniques.
AB  - This paper employs the energy minimum to enhance drug docking efficiency in a
      computer aided drug design (CADD) system. The energy minimum application is used
      to enhance CADD docking performance. The proposed method is discussed in three
      aspects, adaptive genetic algorithms (AGA), Lyapunov stability theorem and
      molecular force field. As in previous researches, docking is the crucial
      component in drug development. The number of docking sites affects the drug
      docking speed. Reducing the scope of the geometric search is the key task. This
      paper proposes AGA to improve geometric molecular docking search efficiency. The
      Lyapunov stability theorem forwards the stability state identification. Protein
      folding intention generally finds the most appropriate stability state when the
      thermodynamic and molecular mechanical free energy has reached the lowest point.
      The AMBER force field simulation is used to discover the molecular statistical
      mechanics in a drug-ligand. AGA was found better in terms of processing the
      geometric graphic search operation. The AGA and Lyapunov algorithms were utilized
      to sieve out the global energy minimum approach from the numerous, raw docking
      sites.

PMID- 20047736
TI  - Ambient air pollution and respiratory health effects in mail carriers.
AB  - Mail carriers represent an occupational group suffering from respiratory symptoms
      and lung function impairment. Although environmental conditions may play role,
      information on the effects of air pollution exposure in this population is
      lacking. The present study was conducted in Athens, Greece, in order to
      investigate the adverse effects of long-term air pollution exposure on
      respiratory outcomes in mail carriers. A total of 226 mail carriers and 73 office
      employees were enrolled. Information on respiratory symptoms, medical,
      occupational, residential and smoking history was obtained through a
      questionnaire. Flow-volume curves were performed in the workplace using a
      portable spirometer. Individualised personal exposure assessment has been applied
      based on long-term residential and occupational subject history linked with
      geographical air pollution distribution. Furthermore, personal measurements were
      obtained for forty-one mail carriers using NO(2) and O(3) passive samplers,
      assuming that current air pollution exposure is sufficiently representative of
      long-term, previous exposure to make a plausible link with current health status.
      The analysis based on exposures estimated on the basis of residential and work
      addresses showed that the most exposed to PM(10) postal workers have rhinitis at
      a higher rate (OR=1.67, 95% CI: 1.01-2.75). In mail carriers there is indication
      that those exposed to higher concentrations of Omicron(3) or PM(10) have a
      greater possibility to present rhinitis (OR=1.63, 95% CI: 0.93-2.88 and OR=1.70,
      95% CI: 0.96-3.03, respectively). The effect of O(3) on rhinitis became even more
      apparent in the analysis based on exposures assessed by personal measurements
      (OR=6.74, 95% CI: 1.24-36.55). Exposure to NO(2) was significantly associated
      with decrements in lung function. For office employees the exposure to air
      pollutants was not associated to any adverse respiratory outcome. Our findings
      suggest that air pollution is a contributing factor for the occurrence of
      rhinitis and lung function impairment in mail carriers.

PMID- 20047737
TI  - Evidence of prokineticin dysregulation in fallopian tube from women with ectopic
      pregnancy.
AB  - OBJECTIVE: To demonstrate expression and regulation of prokineticins (PROKs) and
      their receptors (PROKRs) in fallopian tube (FT) from women who are not pregnant
      and women with ectopic pregnancy (EP). DESIGN: Tissue analysis. SETTING: Large
      United Kingdom teaching hospital. PATIENT(S): Women undergoing hysterectomy for
      benign gynecological conditions (n = 15) and surgery for EP (n = 16).
      INTERVENTION(S): Quantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) and immunohistochemistry were used to determine FT PROK/PROKR messenger RNA
      (mRNA) expression and protein localization, respectively. The PROK/PROKR levels
      were measured in tubal explant cultures stimulated with estrogen (E) and
      progestogen. MAIN OUTCOME MEASURE(S): Differential expression of PROK and PROKR.
      RESULT(S): The FT PROK2 and PROKR1 mRNA levels were up-regulated during the P
      dominant midluteal phase of the menstrual cycle. Increased PROKR1 expression was
      observed in tubal explant cultures treated with medroxy-progesterone acetate
      (MPA). The PROK and PROKR proteins were localized to the epithelium and smooth
      muscle layers of the FT. The PROKR1 and PROKR2 mRNA levels were lower in FT from
      women with EP compared with nonpregnant FT from the midluteal phase.
      CONCLUSION(S): These data suggest a potential role for PROKs in FT function. The
      PROKs are known to affect smooth muscle contraction in the gut. Dysregulated PROK
      expression in FT could affect FT smooth muscle contractility and embryo-tubal
      transport, providing a potential cause for EP.

PMID- 20047738
TI  - Compliance with methotrexate therapy for presumed ectopic pregnancy in an inner
      city population.
AB  - Fewer than 1 in 5 patients comply with the established follow-up protocol to
      treat presumed ectopic pregnancy medically in an urban clinic population.
      Institutions should consider tracking their patient compliance with follow-up to
      determine the efficacy of their treatment decisions.

PMID- 20047739
TI  - Multicenter observational study on slow-cooling oocyte cryopreservation: clinical
      outcome.
AB  - OBJECTIVE: To evaluate the efficacy of oocyte cryopreservation by a single slow
      cooling protocol involving sucrose (0.2 mol/L) in the freezing solution. DESIGN:
      Observational comparison of the clinical outcome in fresh and frozen thawed
      cycles. SETTING: Public and private IVF centers. PATIENT(S): Infertile couples
      undergoing IVF treatment. INTERVENTION(S): Use of a maximum three oocytes in
      fresh cycles, as established by local law, and cryopreservation and later use of
      surplus oocytes. Likewise fresh cycles, maximum three thawed oocytes were used
      per cycle. All thawed oocytes were microinjected. MAIN OUTCOME MEASURE(S):
      Embryologic and clinical parameters of fresh and thawed cycles. RESULT(S): Two
      thousand forty-six patients underwent 2,209 oocyte retrievals involving oocyte
      cryopreservation. Overall, the survival rate of thawed oocytes was 55.8%. In 940
      thaw cycles, the mean numbers of inseminated oocytes and fertilization rates were
      significantly decreased vs. fresh cycles outcomes (2.6 +/- 0.7 vs. 2.9 +/- 0.2
      and 72.5% vs. 78.3%, respectively), as were the rates of implantation (10.1% vs.
      15.4%), pregnancy rates per transfer (17.0% vs. 27.9%), and pregnancy rates per
      cycle (13.7% vs. 26.2%). Differences in clinical outcome were found among
      centers. A pregnancy rate per thawing cycle above 14% was achieved by most
      clinics. Fifty-seven retrievals involving oocyte cryopreservation achieved a
      pregnancy after fresh embryo replacement. Implantation and pregnancy rates per
      embryo transfer and per thawing cycles were 17.5%, 28.6%, and 24.6%,
      respectively. CONCLUSION(S): Under the conditions tested, the clinical outcome of
      oocyte slow-cooling cryopreservation is reduced compared with fresh cycles.
      Nevertheless, in cases of inapplicability of embryo cryopreservation, oocyte
      cryopreservation should be offered to patients with surplus oocytes.

PMID- 20047740
TI  - Depression: an emotional obstacle to seeking medical advice for infertility.
AB  - OBJECTIVE: To investigate the mental and general health of infertile women who
      had not sought medical advice for their recognized infertility and were therefore
      not represented in clinical populations. DESIGN: Longitudinal cohort study.
      SETTING: Population based. PATIENT(S): Participants in the Australian
      Longitudinal Study on Women's Health aged 28-33 years in 2006 who had ever tried
      to conceive or had been pregnant (n = 5,936). INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Infertility, not seeking medical advice. RESULT(S): Compared with
      fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self
      reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01
      1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30
      12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37),
      or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who
      sought medical advice (n = 728), those who had not sought medical advice (n =
      303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental
      health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49),
      heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89).
      Infertile women who had or had not sought medical advice had similar odds of
      reporting an anxiety disorder or anxiety-related symptoms. CONCLUSION(S): Women
      with self-reported depression were unlikely to have sought medical advice for
      infertility. Depression and depressive symptoms may be barriers to seeking
      medical advice for infertility.

PMID- 20047741
TI  - The relation of goal incongruence and self-control demands to indicators of job
      strain among elderly care nursing staff: a cross-sectional survey study combined
      with longitudinally assessed absence measures.
AB  - BACKGROUND: Formerly unconnected lines of research have shown that both the
      perceived incongruence between personal and organizational goals and meeting self
      control demands at work exert adverse influences on indicators of job strain.
      OBJECTIVES: Going beyond this research and drawing on recently developed
      theoretical notions on self-control depleting a limited control resource, the
      present study examines - in addition to main effects - also interactive effects
      of both stressors on various indicators of strain that include not only self
      report measures (dimensions of burnout, psychosomatic complaints) but also
      absence data (sum of days absent, absence frequency) as behavioural outcome.
      DESIGN: A cross-sectional questionnaire survey was conducted in combination with
      absence data referring to a time period of 12 months after administration of the
      questionnaires. SETTING: A municipal organization for residential elderly care
      with six nursing homes located in a large German city. PARTICIPANTS:
      Questionnaires were distributed to the whole nursing staff of which 242 staff
      members filled in the questionnaire and permitted collecting their absence data
      (67% participation rate). METHODS: In addition to descriptive statistics and
      bivariate correlations, hierarchical moderated regression analyses were
      performed. RESULTS: Findings revealed significant main effects of both predictors
      on the criterion measures with signs corresponding to expectations. Over and
      above these main effects, the two-way interaction between goal incongruence and
      self-control demands added a significant amount of incremental variance to the
      prediction of exhaustion, depersonalization, psychosomatic complaints as well as
      the time lost index of absenteeism. In the measure of absence frequency, this
      interaction failed to reach significance. As hypothesized, the form of the
      interactions indicated that the adverse influences of self-control demands are
      strengthened with an increase in the perceived mismatch between personal and
      organizational goals. CONCLUSIONS: Improving the fit between personal and
      organizational goals and strengthening the individual control resource could make
      health care workers less vulnerable against the depleting effects of meeting self
      control demands at work.

PMID- 20047742
TI  - Stress test with dual isotope studies for the documentation of classical ischemic
      preconditioning.
AB  - OBJECTIVES: We investigated whether myocardial perfusion imaging (MPI) can
      demonstrate the effect of classical preconditioning. METHODS: 21 patients with
      documented coronary artery disease (stenosis>or=70%) underwent two exercise
      stress tests (EST) with concomitant MPI, using TL-201 for the first and
      tetrofosmin-Tc-99m for the second. A third MPI was performed at rest, using Tc
      99m. Total defect score was derived by summing tracer uptake in a 17 segments
      left ventricle model, graded on a 5-point scale. Tomographic images were also
      analyzed quantitatively, to derive the total defect size. RESULTS: Maximum ST
      depression did not differ significantly between the two EST (2.2+/-1 vs 2.2+/-1
      mm, p=NS), however in the second EST longer times for onset of ischemic changes
      (228+/-94 vs 265+/-103 s, p=0.01) and appearance of angina (282+/-153 vs 328+/
      177 s, p=0.04) were observed. Exercise perfusion abnormalities were significantly
      lower in the second MPI, in terms of both total defect score (19.2+/-11.5 vs 10+/
      10.4, p<0.0001) and total defect size (28.3+/-16.9 vs 13.8+/-15.8, p<0.0001).
      CONCLUSION: Significant improvement in perfusion pattern was demonstrated in the
      second MPI, accompanied by delayed appearance of ischemic manifestations. The
      improvement in myocardial perfusion extends far beyond the changes that can be
      attributed to differences in myocardial uptake between tracers, reflecting the
      effect of classical preconditioning.

PMID- 20047743
TI  - Enhanced circulating soluble LR11 in patients with coronary organic stenosis.
AB  - LR11, an LDL receptor family member, is expressed in intimal smooth muscle cells.
      It was found that the soluble form of LR11 (sLR11) is detected in serum, and the
      circulating sLR11 levels are positively correlated with intima-media thickness of
      carotid arteries in dyslipidemic subjects. To clarify the significance of serum
      sLR11, the circulating sLR11 levels in patients with organic coronary stenosis
      and the contributing risk factors for them were studied. The subjects, 150
      patients with symptoms of coronary artery disease, underwent coronary
      angiographic examination, and were divided into sex- and age-matched two groups;
      one is organic coronary stenosis group (OCS) and the other is normal coronary
      group (NC). Serum sLR11 levels were significantly higher in OCS than in NC (4.9+/
      2.7 U vs 3.6+/-1.8 U, p<0.05). Multivariate regression analysis showed that
      circulating sLR11 is independent contributing factor for the OCS, as well as
      diabetes mellitus and dyslipidemia. Among various coronary risk factors for sLR11
      level, HbA1c showed the highest correlation coefficient (p<0.01). These results
      suggest that the circulating sLR11 might reflect coronary organic stenosis, and
      that hyperglycemic condition might be promoting factor for expression of LR11 in
      intimal smooth muscle cells.

PMID- 20047744
TI  - Ala54Thr polymorphism of fatty acid-binding protein 2 gene and fasting blood
      lipids: a meta-analysis.
AB  - OBJECTIVE: The results from the published studies on the association of fatty
      acid-binding protein 2 (FABP2) Ala54Thr polymorphism with dyslipidemia are
      conflicting and inconclusive. In this meta-analysis encompassing all the relevant
      studies, we aimed to investigate the association of the FABP2 Ala54Thr
      polymorphism with fasting blood lipids. METHODS: We limited our analysis to the
      following four blood lipid parameters: total cholesterol (TC), triglycerides
      (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein
      cholesterol (HDL-C). Subjects were confined to adults who were at least 18 years
      old. A dominant model was used for this meta-analysis. RESULTS: 30 studies with
      14,401 subjects were included in this meta-analysis. The results showed that the
      carriers of Thr54 allele have higher blood TC and LDL-C than the non-carriers:
      standardized mean difference (SMD)=0.07, 95% CI (confidence interval, 0.02,
      0.11), P=0.005, Pheterogeneity=0.12, and SMD=0.09, 95% CI (0.03, 0.15), P=0.002,
      Pheterogeneity=0.0006, respectively. Significant association between the Ala54Thr
      polymorphism and lower blood HDL-C was also detected under the dominant models:
      SMD=-0.05, 95% CI (-0.09, -0.00), P=0.04, Pheterogeneity=0.10. CONCLUSIONS: Our
      meta-analysis supports the strong association between the Thr54 allele of the
      FABP2 Ala54Thr polymorphism with higher levels of TC and LDL-C, and lower levels
      of HDL-C.

PMID- 20047745
TI  - Decreased apolipoprotein A5 is implicated in insulin resistance-related
      hypertriglyceridemia in obesity.
AB  - Hypertriglyceridemia is associated insulin resistance in obese people. Recently
      identified apolipoprotein A5 (apoA5) is involved in triglyceride (TG) metabolism.
      This study was to investigate the role of apoA5 in insulin resistance-related
      hypertriglyceridemia in obesity. 682 participants including 340 non-obese
      individuals and 342 obese individuals were recruited in this study. Plasma apoA5
      levels were measured. The insulin resistance in participants was assessed by
      homeostasis model assessment of insulin resistance (HOMA-IR). An insulin
      resistant and hypertriglyceridemic rat model was established by high-fructose
      diet with obese Zucker rats as positive controls. Besides, two insulin resistant
      models in vitro were induced by insulin and tumor necrosis factor-alpha
      (TNFalpha) in HepG2 cells. Obese participants had lower plasma apoA5 levels.
      Plasma apoA5 levels were inversely correlated with TG, body mass index and HOMA
      IR in humans. Furthermore, hepatic and plasma apoA5 reduced in fructose-fed rats
      whereas no significant changes of apoA5 were observed in obese Zucker rats. In
      addition, treatment of HepG2 cells with insulin and TNFalpha decreased apoA5
      expression and increased TG content. Thus, decreased apolipoprotein A5 is
      implicated in insulin resistance-related hypertriglyceridemia in obesity.

PMID- 20047746
TI  - Assessment of amputee socket-stump-residual bone kinematics during strenuous
      activities using Dynamic Roentgen Stereogrammetric Analysis.
AB  - The design, construction, and fitting of artificial limbs remain to this day an
      art, dependent on the accumulated expertise of the practitioner/prosthetist.
      Socket fitting is cost ineffective, time consuming, and a source of inconvenience
      for the amputee. Stump-skin slippage within the socket can cause discomfort,
      internal limb pain, and eventually skin ulcers as a result of excessive pressure
      and shear within the socket. This study presents a new method of assessment of
      three-dimensional (3D) socket-stump kinematics/slippage of strenuous activities
      using Biplane Dynamic Roentgen Stereogrammetric Analysis instrumentation. Ten
      below knee amputees participated in the study. A more holistic representation of
      the downward slippage trend of all proximal side skin markers with respect to the
      socket, and an even more characteristic and of higher magnitude downward-and
      anterioposterior slippage (maximum slippage: 151 mm for the fast-stop task and 19
      mm for the step-down task) between the distal markers after impact, was possible
      for both tasks for all amputees. Displacement between skin-to-skin marker pairs
      reached maximum values of approximately 10mm for the step-down trials and up to
      24 mm for the fast stop trials. Maximum skin strain was dependent on the position
      of the skin markers. Distally positioned skin marker pairs demonstrated mainly
      anterioposterior displacement between each other (maximum relative strain: 13
      14%). Maximum relative strain for the proximal markers was 8-10%. This highly
      accurate, in-vivo, patient-specific, unobtrusive dynamic information, presented
      using 3D visualization tools that were up to now unavailable to the clinician
      prosthetist, can significantly impact the iterative cycle of socket fitting and
      evaluation.

PMID- 20047747
TI  - The influence of sagittal center of pressure offset on gait kinematics and
      kinetics.
AB  - OBJECTIVES: Kinetic patterns of the lower extremity joints have been shown to be
      influenced by modification of the location of the center of pressure (CoP) of the
      foot. The accepted theory is that a shifted location of the CoP alters the
      distance between the ground reaction force and the center of the joint, thereby
      modifying torques during gait. Various footwear designs have been reported to
      significantly alter the magnitude of sagittal joint torques during gait. However,
      the relationship between the CoP and the kinetic patterns in the sagittal plane
      has not been examined. The aim of this study was to evaluate the association
      between the sagittal location of the CoP and gait patterns during gait in healthy
      men. METHODS: A foot-worn biomechanical device which allows controlled
      manipulation of the CoP location was utilized. Fourteen healthy men underwent
      successive gait analysis with the device set to convey three different sagittal
      locations of the CoP: neutral, anterior offset and posterior offset. RESULTS: CoP
      translation in the sagittal plane (i.e., from posterior to anterior)
      significantly related with an ankle dorsiflexion torque and a knee extension
      torque shift throughout the stance phase. Likewise, an anterior translation of
      the CoP significantly reduced the extension torque at the hip during pre-swing.
      CONCLUSIONS: The study results confirm a direct correlation between sagittal
      offset of the CoP and the magnitude of joint torques throughout the lower
      extremity.

PMID- 20047748
TI  - Finite element analysis of barbed sutures in skin and tendon tissues.
AB  - Barbed surgical sutures are a new type of knotless suture that are currently
      being used clinically in cosmetic and plastic surgery procedures for faster
      healing and better cosmesis. Clinical studies are also underway to evaluate their
      performance in other deep tissue applications. However, little is known about
      their intrinsic mechanical behavior and their interactions with surrounding
      tissues. The primary objective of the current study was to analyze the mechanical
      behavior of barbed sutures using a finite element analysis approach. First, the
      effect of applying a point-pressure load to the tip of the barb and measuring its
      effect on barb displacement was studied. Second, the effect of an applied
      displacement to a barb anchored either in skin or tendon material for both the
      suture and the surrounding tissue. The results indicate that the flexibility of
      the barb can be increased or decreased by changing the barb geometry. It was
      concluded that the barb geometry and design need to be modified for use with
      different types of tissue. For example, in order to achieve the best mechanical
      anchoring with skin tissue the barb should be more flexible compared to the one
      designed to work with tendon tissue. The uniqueness of this study is that it is
      the first to establish a virtual prototyping and designing method for barbed
      sutures. For example, a new and improved virtual design of barb geometry is
      proposed and validated. It also provides the first report on how to develop a
      virtual bench top suture/tissue pullout testing environment.

PMID- 20047749
TI  - A new method for gravity correction of dynamometer data and determining passive
      elastic moments at the joint.
AB  - Moments measured by a dynamometer in biomechanics testing often include the
      gravitational moment and the passive elastic moment in addition to the moment
      caused by muscle contraction. Gravitational moments result from the weight of
      body segments and dynamometer attachment, whereas passive elastic moments are
      caused by the passive elastic deformation of tissues crossing the joint being
      assessed. Gravitational moments are a major potential source of error in
      dynamometer measurements and must be corrected for, a procedure often called
      gravity correction. While several approaches to gravity correction have been
      presented in the literature, they generally assume that the gravitational moment
      can be adequately modeled as a simple sine or cosine function. With this
      approach, a single passive data point may be used to specify the model, assuming
      that passive elastic moments are negligible at that point. A new method is
      presented here for the gravity correction of dynamometer data. Gravitational
      moment is represented using a generalized sinusoid, which is fit to passive data
      obtained over the entire joint range of motion. The model also explicitly
      accounts for the presence of passive elastic moments. The model was tested for
      cases of hip flexion-extension, knee flexion-extension, and ankle plantar flexion
      dorsiflexion, and provided good fits in all cases.

PMID- 20047751
TI  - Development of an ultra-high-pressure liquid chromatography-tandem mass
      spectrometry multi-residue sulfonamide method and its application to water,
      manure slurry, and soils from swine rearing facilities.
AB  - An analytical method was developed using ultra-high-pressure liquid
      chromatography-triple quadrupole-tandem mass spectrometry (UHPLC-TQ-MS/MS) to
      simultaneously analyze 14 sulfonamides (SA) in 6 min. Despite the rapidity of the
      assay the system was properly re-equilibrated in this time. No carryover was
      observed even after high analyte concentrations. The instrumental detection limit
      based on signal-to-noise ratio (S/N)>3, was below 1 pg/microL (5 pg on column)
      for all SAs except sulfachloropyridazine. Surface water, ground water, soil, and
      slurry manure contained in storage ponds in and around swine [Sus scrofa
      domesticus] rearing facilities were analyzed. Sample cleanup for ground water and
      surface water included using solid phase extraction (SPE) using Oasis hydrophilic
      lipophilic balance (HLB) cartridges. The soil and slurry manure required tandem
      strong anion exchange (SAX) and HLB solid phase extraction cartridges for sample
      cleanup. With few exceptions, the recoveries ranged from 60 to 100% for all
      matrices. The minimum detectable levels were below 2.0 ng/L for water, 30 ng/L
      for slurry manure, and 45 ng/kg for soil except for sulfachloropyridazine. The
      coefficient of variation (CV) was within 20% for most of the compounds analyzed.
      Using this method, sulfamethazine concentrations of 2250-5060 ng/L,
      sulfamethoxazole concentrations of 108-1.47 x 10(6)ng/L, and sulfathiazole
      concentrations of 785-1700 ng/L were found in the slurry manure. Sulfadimethoxine
      (2.0-32 ng/L), sulfamethazine (2.0-5.1 ng/L), and sulfamethoxazole (20.5-43.0
      ng/L) were found in surface water and ground water. In top soil (0-15 cm),
      sulfamethazine ranged 34.5-663 ng/kg dry weight in those locations that received
      slurry manure as a nutrient; no SAs were found in the soil depths between 46 and
      61 cm. The speed makes the method practical for medium to high throughput
      applications. The sensitivity and positive analyte identification make the method
      suitable for the demanding requirements for real world applications.

PMID- 20047750
TI  - Rapid magnetic-mediated solid-phase extraction and pre-concentration of selected
      endocrine disrupting chemicals in natural waters by poly(divinylbenzene-co
      methacrylic acid) coated Fe3O4 core-shell magnetite microspheres for their liquid
      chromatography-tandem mass spectrometry determination.
AB  - A new Fe(3)O(4)/poly(divinylbenzene-co-methacrylic acid) core-shell magnetite
      microspheric material have been successfully developed as magnetic-mediated solid
      phase extraction micro-particle sorbent in dispersion mode (MM-SPE-MP) for the
      determination of selected estrogenic endocrine disrupting chemicals (EDCs),
      namely: estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha
      ethynylestradiol (EE2) and bisphenol-A (BPA), in natural water, via
      quantification by HPLC tandem mass spectrometry. The magnetite Fe(3)O(4) core of
      this MM-SPE-MP sorbent was fabricated by a solvothermal approach and the thin
      layer of amphipolar poly(divinylbenzene-co-methacrylic acid) (pDVB-MAA) coating
      was established via suspension polymerization. The resultant core-shell MM-SPE-MP
      sorbent material was characterized by electron microscopy, X-ray diffraction and
      Fourier-transformed infrared spectroscopy. Particle size distribution of the core
      shell microspheres was within the range 300-700 nm in diameter and the thickness
      of the pDVB-MAA coating was ca. 10nm. This magnetite microspheric material can be
      easily dispersed in aqueous samples and retrieved by the application of external
      magnetic field via a small piece of permanent magnet. The MM-SPE-MP process for
      the selected estrogenic EDCs involved the dispersion of the core-shell
      microspheric sorbent in water samples with sonication, followed by magnetic aided
      retrieval of the sorbent and solvent (methanol) desorption of extracted EDCs for
      LC-MS/MS analysis. Partition equilibrium for all the selected EDCs onto this MM
      SPE-MP sorbent was achieved within 15 min. Recoveries of the EDCs were in ranges
      of 56-111%. Analytes with smaller K(OW) value showed relatively lower recovery
      (and relatively longer equilibration time for partitioning). Method detection
      limits achieved were found to be 1-36 pg ml(-1) (n=3), while the repeatability
      was 6-34% (p<0.05, n=3). This work demonstrates the usefulness of MM-SPE-MP in
      the rapid and highly sensitive monitoring of trace organic contaminants in
      natural waters.

PMID- 20047752
TI  - Macromolecular replication during lignin biosynthesis.
AB  - Lignins play a crucial role in the cell-wall architecture of all vascular plants.
      They are composed of p-hydroxyphenylpropanoid units interconnected through
      covalent bonds formed during lignol radical coupling between six different pairs
      of atomic centers. For 50years, the primary structures of lignins have been
      thought to be random, but for a number of reasons such an assumption is not
      tenable. For example, it has been reported that, by simple physicochemical means,
      the rather recalcitrant lignins in spruce wood can be decisively separated into
      two fractions containing quite dissimilar biopolymer chains. Thus, a paradigm
      shift should be imminent, and a detailed working hypothesis for the mechanism of
      lignin biosynthesis would be invaluable in delineating how the process of
      macromolecular lignin assembly can be properly investigated. In conjunction with
      an earlier experimental result, an explicit model for a template
      dehydropolymerization process has been developed that describes how lignin
      primary structure is replicated. The strengths of the powerful noncovalent
      interactions have been calculated that control the transient placement of lignol
      radicals about to undergo coupling on a double-stranded lignin template. These
      elementary steps engender, in the growing daughter chain, a primary structure
      identical to that of the distal template strand. The interactions are governed by
      dynamical electron correlation in the pi-orbitals of each immobilized lignol
      radical and the complementary aromatic ring in the antiparallel proximal strand.
      The resulting noncovalent forces are computed to be stronger than those
      stabilizing GC/CG base pairs in DNA double-helices, but the mechanism of
      replication is fundamentally different from that of any other biopolymer.

PMID- 20047753
TI  - Uterine natural killer (uNK) cells and their missions during pregnancy: a review.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system. The aim of
      this review is to describe the properties and roles of NK cells in the human
      uterus during pregnancy. Uterine natural killer cells (uNK) constitute a major
      lymphocyte population during early gestation in the uterus. The uterine natural
      killer cells are recognized owing to their CD56(bright), CD16(-), CD3(-)
      phenotype. Their number increases in the first trimester with a subsequent
      decline as pregnancy progresses. They have been shown to be closely associated
      with cells of the extravillous trophoblast (EVT) and spiral arteries. They play
      important roles in remodeling of the spiral arteries, control of trophoblast
      invasion and in the development of the placenta. Some studies have shown the
      number and repertoire of receptors of uNK differ between women with healthy
      pregnancies and those with pathologic pregnancies, such as pre-eclampsia or
      intrauterine growth retardation. During pregnancy, the cytotoxic characteristics
      of the uterine killer cells are not directed towards the fetus, and scientists
      continue to question and explore this phenomenon with increasing evidence that
      these cells may perform differing beneficial roles during pregnancy. Contrary to
      their previously suspected "hostile" characteristics, the uterine killer cells
      are considered to be "friendly" and appear to be essential and very important
      regulators of successful implantation and pregnancy.

PMID- 20047754
TI  - Changes in the gene expression of adiponectin and adiponectin receptors (AdipoR1
      and AdipoR2) in ovarian follicular cells of dairy cow at different stages of
      development.
AB  - Adiponectin is one of the most important, recently discovered adipocytokines that
      acts at various levels to control male and female fertility through central
      effects on the hypothalamus-pituitary axis or through peripheral effects on the
      ovary, uterus, and embryo. We studied simultaneous changes in the gene expression
      pattern of adiponectin and adiponectin receptors 1 and 2 (AdipoR1 and AdipoR2) in
      granulosa and theca cells, cumulus-oocyte complex, and in corpus luteum in
      healthy bovine (Bos tarus) follicles at different stages of development. The
      expression levels of adiponectin, AdipoR1, and AdipoR2 mRNA were lower (P<0.05)
      in granulosa and cumulus cells in comparison with that in theca cells and oocyte.
      In contrast with the oocyte, AdipoR1 in granulosa, theca, and luteal cells was
      expressed (P<0.05) more than AdipoR2. Adiponectin expression increased (P<0.05)
      in granulosa cells and in cumulus-oocyte complex during follicular development
      from small to large follicles. Opposite results were observed in theca cells.
      Expression of adiponectin was highest in the late stages of corpus luteum (CL)
      regression, whereas lower expression was recorded in active CL (P<0.05). AdipoR1
      and AdipoR2 expression increased during the terminal follicular growth in
      granulosa and theca cells (P<0.05) and during the luteal phase progress in CL.
      There was positive correlation between adiponectin mRNA level in granulosa cells
      from large follicles and follicular fluid estradiol concentration (r=0.48,
      P<0.05) and negative correlation between adiponectin mRNA abundance in theca
      cells and follicular fluid progesterone concentration (r=-0.44, P<0.05). In
      conclusion, we found that the physiologic status of the ovary has significant
      effects on the natural expression patterns of adiponectin and its receptors in
      follicular and luteal cells of bovine ovary.

PMID- 20047755
TI  - Seasonal variations in seminal plasma and sperm characteristics of wild-caught
      and cultivated Atlantic cod, Gadus morhua.
AB  - The objective was to investigate changes, throughout the spawning season, in body
      size attributes and quantitative semen characteristics of wild-caught and
      cultivated Atlantic cod, Gadus morhua L. Sperm velocity increased significantly
      throughout the spawning season of cod from both origins. Curvilinear velocity
      (VCL; 30 sec post-activation) increased from 78.9+/-6.5 to 128.2+/-6.5 microm/sec
      (mean+/-SEM) between the beginning and end of the spawning season, respectively,
      for wild-caught cod, whereas for cultivated fish, it increased from 26.6+/-2.4 to
      48.9+/-3.1 microm/sec between January and March. Spermatocrit did not undergo a
      significant seasonal change in wild-caught cod but did thicken for cultivated cod
      (24.6+/-4.2% in January to 40.5+/-4.4% in April; P<0.01). Sperm head area,
      perimeter, length, and width declined significantly at the end of the spawning
      season of cod from both origins (all P values<0.01). Seminal plasma osmolality
      and Na(+) ion concentration followed a dome-shaped function through the spawning
      season for both wild-caught and cultivated cod (P<0.05). For cultivated cod,
      seminal plasma pH was significantly lower at the start of the spawning season
      (P<0.001), whereas Ca(2+) increased then decreased (P<0.05). Body size
      attributes, spermatocrit, and seminal plasma constituents had significant
      relationships with sperm activity variables. These relationships varied as a
      function of time post-activation, month, and fish origin. Our findings may be
      used to (i) assess spermiation stage without killing males; (ii) optimize semen
      collection for hatchery production; (iii) characterize the potential impact of
      farming on sperm quality; and (iv) improve success of sperm cryopreservation and
      short-term storage.

PMID- 20047756
TI  - Quantification of dental erosion--a comparison of stylus profilometry and
      confocal laser scanning microscopy (CLSM).
AB  - OBJECTIVES: Since stylus profilometry applies a force on the sample surface, it
      is logical to hypothesize that the profilometer penetrates the surface of the
      enamel softened by acid solutions. The aims of the present study were, therefore,
      to test the hypothesis that surface profilometry measurements of eroded enamel
      alter the surface of the enamel, to quantify the potential effect of the surface
      alteration (scratches) on the measured values of enamel erosion by atomic force
      microscopy and to compare the values of enamel loss caused by erosion as measured
      by profilometry and non-contact confocal laser scanning microscopy (CLSM).
      METHODS: Enamel samples, cut from unerupted human third molars were treated with
      Volvic Mineral Water and citric acid solutions of different pH values. The enamel
      material loss was measured by two different contact profilometers and a
      reflection mode CLSM. The scratches depth was analyzed by atomic force
      microscopy. RESULTS: Our study demonstrated that the tip of the profilometer
      penetrated the surface of eroded enamel during the profilometry measurements,
      leading to clearly visible surface scratches on the enamel samples. The
      profilometers created surface scratches of a depth ranging from 57.6 (47.1)nm to
      577.1 (157.6)nm on the surface of the eroded enamel and led, therefore, to a
      larger measured value of erosion. It was shown that the depth of the scratches
      depends on the pH value, the erosion time and the profilometer used.
      SIGNIFICANCE: With few exceptions profilometers deliver reliable values of
      erosive enamel material loss, although they create surface scratches on eroded
      enamel. Reflection mode CLSM is a non-tactile, fast and precise method for
      analyzing enamel erosion quantitatively in vitro.

PMID- 20047757
TI  - New zirconia primer improves bond strength of resin-based cements.
AB  - OBJECTIVE: Various chemical interactions can be used to develop ceramic-resin
      bonding and specific approaches are available for zirconia ceramics. This study
      evaluated the effect of a new experimental primer, a mixture of organophosphate
      and carboxylic acid monomers, on the zirconia-to-resin shear bond strength (SBS).
      METHODS: Forty Y-TZP blocks (15x4x2mm) were embedded in an acrylic resin base,
      polished, Al(2)O(3)-sandblasted and randomly divided into eight groups. Three
      different resin-based luting agents (BisCem, Duo-Link, Panavia F) were used to
      build 2.4mm-diameter cylinders (n=15) onto the zirconia surface with and without
      the new experimental zirconia primer. The new primer was also tested with Z100
      restorative composite resin cylinders. In addition, Panavia was used with its own
      primer (Clearfil Ceramic Primer). SBS testing was carried out after 24h of
      storage in water. Scanning electron microscopy (SEM) was used to evaluate the
      zirconia surface topography and failure mode. RESULTS: According to ANOVA and
      Tukey test (alpha=0.05), the association of the experimental primer with the
      restorative composite resin Z100 yielded the highest SBS (29.35MPa) followed by
      DuoLink with the new primer (26.68MPa). The groups that did not receive the
      experimental primer presented the lowest SBS values (from 5.95 to 9.79MPa). The
      failure mode was adhesive for the non-primed specimens and predominantly mixed in
      the primed groups. SIGNIFICANCE: The use of the new zirconia experimental primer
      based on organophosphate/carboxylic acid monomers increased the bond strength of
      different resin-based luting agents including Z100 restorative material.

PMID- 20047758
TI  - A versatile pH sensitive chondroitin sulfate-PEG tissue adhesive and hydrogel.
AB  - We developed a chondroitin sulfate-polyethylene glycol (CS-PEG) adhesive hydrogel
      with numerous potential biomedical applications. The carboxyl groups on
      chondroitin sulfate (CS) chains were functionalized with N-hydroxysuccinimide
      (NHS) to yield chondroitin sulfate succinimidyl succinate (CS-NHS). Following
      purification, the CS-NHS molecule can react with primary amines to form amide
      bonds. Hence, using six arm polyethylene glycol amine PEG-(NH2)6 as a crosslinker
      we formed a hydrogel which was covalently bound to proteins in tissue via amide
      bonds. By varying the initial pH of the precursor solutions, the hydrogel
      stiffness, swelling properties, and kinetics of gelation could be controlled. The
      sealing/adhesive strength could also be modified by varying the damping and
      storage modulus properties of the material. The adhesive strength of the material
      with cartilage tissue was shown to be ten times higher than that of fibrin glue.
      Cells encapsulated or in direct contact with the material remained viable and
      metabolically active. Furthermore, CS-PEG material produced minimal inflammatory
      response when implanted subcutaneously in a rat model and enzymatic degradation
      was demonstrated in vitro. This work establishes an adhesive hydrogel derived
      from biological and synthetic components with potential application in wound
      healing and regenerative medicine.

PMID- 20047759
TI  - DNA/polyethyleneimine/hyaluronic acid small complex particles and tumor
      suppression in mice.
AB  - The highest barriers for non-viral vectors to an efficient in vivo gene
      transfection would be (1) non-specific interaction with biological molecules, and
      (2) large size of the DNA complex particles. Protective coating of the
      DNA/polyethyleneimine (PEI) complexes by hyaluronic acid (HA) effectively
      diminished the adverse interactions with biological molecules. Here we found HA
      also protected the DNA/PEI complexes against aggregation and inactivation through
      lyophilization-and-rehydration procedures. It allows us to prepare the
      concentrated very small DNA complex particles (<70 nm) suspension by preparing
      the complexes at highly diluted conditions, followed by lyophilized-and
      rehydrated to a small volume. In vivo gene expression efficiency of the small
      complex was examined with mice subcutaneously inoculated with B16 melanoma cells.
      These formulations showed high reporter-gene expression level in tumor after
      intravenous injection into tumor-bearing mice. Small complex was then made of the
      plasmid encoding GM-CSF gene, and injected into the mice bearing subcutaneous
      solid B16 tumor. After intravenous injection, it induced apparent tumor growth
      suppression in 50% of the mice. Notably, significant therapeutic effect was
      detected in the mice that received intratumoral injection, and 75% of the mice
      were completely cured with disappearance of tumor.

PMID- 20047760
TI  - Temporal and spatial variations of water quality in the Jinshui River of the
      South Qinling Mts., China.
AB  - Water pollution has become a growing threat to human society and natural
      ecosystems in recent decades, increasing the need to better understand the
      spatial and temporal variabilities of pollutants within aquatic systems. This
      study sampled water quality at 12 sampling sites from October 2006 to August 2008
      in the Jinshui River of the South Qinling Mts., China. Multivariate statistical
      techniques and gridding methods were used to investigate the temporal and spatial
      variations of water quality and identify the main pollution factors and sources.
      Two-way analysis of variance (ANOVA) showed that 25 studied water quality
      variables had significant temporal differences (p<0.01) and spatial variability
      (p<0.01). Using cluster analysis, the 12 sampling sites were classified into
      three pollution level groups (no pollution, moderate pollution, and high
      pollution) based on similarity of water quality variables. Factor analysis
      determined that 80.4% of the total variance was explained by five factors, that
      is, salinity, trophicity, organic pollution, oxide-related process, and erosion.
      The gridding methods illustrated that water quality progressively deteriorated
      from headwater to downstream areas. The analytical results suggested that the
      water pollution primarily resulted from domestic wastewater and agricultural
      runoff, and provided critical information for water resource conservation in
      mountainous watersheds of the South Qinling Mts., China.

PMID- 20047761
TI  - Metal and metallothionein content in bullfrogs: study of a whole watershed
      impacted by agricultural activities.
AB  - Among the various anthropogenic activities potentially affecting amphibian
      populations, agriculture has often been evoked. Fertilizers used in agriculture
      are documented sources of metals that may contaminate nearby rivers. Bullfrogs
      (Rana catesbeiana) were collected within the Yamaska River basin (Quebec, Canada)
      along a gradient of agricultural land use intensity. Hepatic, renal and
      intestinal metal content, along with hepatic metallothionein content, were
      determined. In general, dissolved metal concentrations and accumulated metal
      concentrations in bullfrogs varied little among sites. Hepatic Cu and Zn
      concentrations were significantly different among subwatersheds and were in
      accordance with the gradient in agricultural activities in at least one of the
      three years studied. Liver metallothionein content did not vary significantly
      among the subwatersheds, but they were correlated with Cu content within two
      sites and Cd content at one site. We conclude that R. catesbeiana could be used
      as a biomonitor for Cu contamination and potentially for other metals.

PMID- 20047762
TI  - Use of the Nominal Group Technique (NGT) to understand the perceptions of the
      healthiness of foods associated with African Americans.
AB  - PURPOSE: To determine the degree of overlap between foods considered part of
      African American (AA) culture and those considered to be healthy. METHODS: A
      total of 44 AA men and women were recruited from the Birmingham, AL area, 25
      years of age and older to participate in four Nominal Group Technique (NGT)
      meetings. Participants from the first two groups generated 90 unique food items
      in response to the question "What are the foods you associate with being African
      American?" Participants individually ranked their top three most unhealthy foods.
      The next two groups generated 116 unique food items in response to the question
      "What foods do you consider to be healthy?" Participants individually ranked
      their top three foods that were considered most associated with AA. RESULTS: The
      top five foods associated with AA were chitterlings, fried chicken, pig parts,
      greens prepared with ham hock, and pork ribs. Of the foods associated with AA,
      chitterlings, pig parts, fatback, fried chicken, and greens prepared with ham
      hocks were ranked as the unhealthiest. The top five healthy foods were broccoli,
      boiled greens, baked fish, grapefruit, and broiled fish. From these top five
      healthy foods, only boiled greens were considered to be associated with AA.
      CONCLUSIONS: Many of the foods AA consider as traditional foods are also
      perceived as unhealthy. On the contrary, foods perceived to have the most health
      value may not be a routine part of AA food patterns. Understanding AA perceptions
      of the healthfulness of foods can be informative for culturally appropriate
      nutrition intervention development.

PMID- 20047763
TI  - Monoclonal antibodies specific for discontinuous epitopes direct refolding of
      influenza A virus hemagglutinin.
AB  - Antibodies (Abs) specific for the globular domain of influenza A virus
      hemagglutinin (HA) efficiently neutralize viral infectivity and provide the most
      effective protection against influenza following infection or vaccination. Nearly
      all neutralizing Abs recognize discontinuous determinants formed by residues
      present on different stretches of the HA primary structure. Here, I show that
      approximately 25% of a large panel of neutralizing monoclonal Abs (mAbs),
      including Abs specific for each of the four major antigenic sites, can bind to
      completely denatured HA. Binding of these mAbs to denatured HA occurs much more
      slowly than binding to native HA, but bound mAbs dissociate from denatured and
      native HA with similar kinetics, and amino acid substitutions that reduce mAb
      binding to native HA have a similar effect on mAb interaction with denatured HA.
      HA refolding induced by mAb binding facilitated the binding of mAbs to other
      antigenic sites, indicating that refolding was not limited to the antibody
      interaction domain. These findings validate the localization of antigenic sites
      by identifying amino acid substitutions selected in mAb escape mutants. Further,
      they demonstrate that Abs can facilitate the refolding of denatured proteins,
      which suggests a number of practical applications for optimizing antibody based
      assays, and also for potentially using Abs as specific chaperones for protein
      refolding.

PMID- 20047764
TI  - Direct binding of TRAF2 and TRAF6 to TICAM-1/TRIF adaptor participates in
      activation of the Toll-like receptor 3/4 pathway.
AB  - Using yeast two-hybrid screening, we found three TRAF proteins TRAF1, 2 and 6,
      bound the N-terminal region of the TLR3/4 adaptor TICAM-1 (TRIF). TRAF2, a newly
      identified TICAM-1-binding protein, bound the PxQxS motif (aa 333-338) of TICAM-1
      using mutagenesis by alanine substitutions. TICAM-1 is known to induce the
      activation of NF-kappaB and IRF-3, which leads to activation of the interferon
      (IFN)-beta promoter, an activity that is conserved in the N+TIR fragment (aa 1
      533). By mutation of the two distinct binding sites for TRAF2 and TRAF6 in N+TIR
      TICAM-1, the induction of IFN-beta was completely abrogated. Although the TRAF2
      site single mutation only marginally affected TICAM-1-mediated type I IFN
      induction, it further impaired the function of the TRAF6 site mutant. Moreover,
      double point mutations of the TRAF2 and TRAF6 binding motifs in TICAM-1 N+TIR
      reduced the activation of IRF-3 and NF-kappaB, the critical transcription factors
      for IFN-beta expression. Furthermore, TRAF2/6 functioned as an E3 ligase to
      induce K63-mediated ubiquitination on N+TIR which was abrogated in the mutant
      lacking the TRAF2/6 sites in parallel with IFN-inducing activity. Confocal
      microscopy analysis indicated that TRAF2 and TRAF6 merged with oligomerized (i.e.
      activated) TICAM-1 N+TIR. However, TRAF3, which is another TRAF family member
      essential for TLR3-mediated type-I IFN signaling, still assembled in the mutant
      lacking the TRAF2/6 sites. Our data suggest that the binding of TRAF2 and TRAF6
      to TICAM-1 cooperatively activates the IFN-inducing pathway through
      ubiquitination of TICAM-1, a modification which occurs unrelated to TRAF3
      recruitment in the TICAM-1 signaling complex. TRAF2/6 may participate in TICAM-1
      mediated IFN-beta induction besides TRAF3.

PMID- 20047765
TI  - UV radiation in marine ectotherms: molecular effects and responses.
AB  - This review summarizes current knowledge on ultraviolet radiation (UVR)-induced
      cellular and molecular damage in marine ectotherms (invertebrates and fish). UVR
      impairs sperm motility, reduces fertilization, and causes embryo malformation
      that in turn affects recruitment and therefore the sustainability of natural
      populations. The direct molecular effects of UVR are mediated by absorption of
      certain wavelengths by specific macromolecules and the dissipation of the
      absorbed energy via photochemical reactions. Most organisms have defense
      mechanisms that either prevent UVR-induced damage, or mechanisms that repair the
      damage. Photoprotective pigments, antioxidant defense compounds, and cell cycle
      development genes are some of the molecules involved in UVR defense.
      Photoenzymatic repair and nucleotide excision repair are the two primary DNA
      repair systems in marine ectotherms. We anticipate that toxicogenomic studies
      will gain importance in UVR research because they can elucidate the primary
      processes involved in UVR damage and the cellular response to this damage.

PMID- 20047766
TI  - Seasonal variation in mitochondrial responses to cadmium and temperature in
      eastern oysters Crassostrea virginica (Gmelin) from different latitudes.
AB  - Cadmium (Cd) is an important environmental pollutant that can lead to impairment
      of cellular functions, energy misbalance and negatively impact survival in
      estuarine organisms including oysters. Like other marine bivalves, oysters can
      accumulate high Cd burdens in their tissues and are susceptible to the toxic
      effects of this metal. Presently, the factors that affect sensitivity to Cd
      toxicity and its variation in wild oyster populations are poorly understood. We
      analyzed geographical and seasonal variability of mitochondrial responses to
      elevated temperatures and Cd stress in eastern oysters Crassostrea virginica from
      populations adapted to different thermal regimes (subtropical Texas (TX), warm
      temperate North Carolina (NC) and cold temperate Washington (WA) areas).
      Seasonality had a strong effect on mitochondrial function in oysters from the two
      studied southern populations (TX and NC) but not in their northern (WA)
      counterparts, with decreased mitochondrial abundance and increased rates of
      mitochondrial proton leak in gill tissues of TX and NC oysters in summer.
      Compared to WA oysters, oysters from the two southern populations accumulated Cd
      faster in their tissues, and their mitochondria were more sensitive to Cd
      inhibition in resting and ADP-stimulated states at 20 and 28 degrees C. At 12
      degrees C, inter-populational differences in Cd accumulation rates and
      sensitivity of mitochondrial respiration to Cd were not significant. Within each
      of the three studied populations, sensitivity of mitochondrial ADP-stimulated
      respiration to Cd inhibition increased with increasing temperatures (28>20>12
      degrees C). This indicates that oysters from the two southern sites may be more
      vulnerable to Cd toxicity due to exposure to high environmental temperatures in
      summer, elevated rates of Cd accumulation and high intrinsic sensitivity of their
      mitochondria to Cd. This study suggests that data on sensitivity to pollutants
      obtained for one population of oysters should be extrapolated to other
      conspecific populations with caution and that regulatory standards for water
      pollution based on the studies from one geographical region may not be protective
      for other areas.

PMID- 20047767
TI  - Consumer panel study on elderly people's wishes concerning services.
AB  - This study informs on the wishes and needs of elderly people themselves regarding
      services for the elderly. The data for the study were gathered using a consumer
      panel method. Elderly people desire assistance in heavy cleaning chores, in
      outdoor activities and in carrying out their personal business. Elderly people
      felt that there should be more recreational services available. Elderly people
      link aging with feelings of insecurity and loneliness. Becoming a service user
      for the first time is felt to be a very difficult step to take, and so this
      decision is postponed as long as possible. The elderly people desire a service
      for assessing their individual service needs in an organized, expert and
      objective fashion. The study indicates that elderly people value the human
      contact gained through service provision. The consumer panel method for
      collecting data was successful.

PMID- 20047768
TI  - Impact of type 2 diabetes mellitus on prescription medication burden and out-of
      pocket healthcare expenses.
AB  - AIMS: The number of prescription medications and out-of-pocket expenses of
      individuals with type 2 diabetes mellitus (T2DM) were evaluated to assess the
      economic burden of diabetes. METHODS: The self-reported number of prescription
      medications and out-of-pocket healthcare expenses were evaluated from respondents
      of the United States SHIELD study with and without a diagnosis of T2DM.
      Medications included monotherapy and combination therapy; combination tablets
      were counted as one agent. Analysis of variance and multivariate linear
      regression models adjusted for age, gender, prescription insurance coverage, and
      household income. RESULTS: Of the T2DM respondents (n=3551), 40% were on 1
      prescription antidiabetic agent (7% insulin alone), 26% were on 2 agents, 8% were
      on >or=3 agents, with a mean of 1.3 antidiabetic agents. After adjusting for age,
      gender, insurance coverage, and income, respondents with T2DM had a significantly
      larger total number of prescriptions (6.2) and higher out-of-pocket expenses for
      both annual medical ($1158) and monthly prescription ($144) expenses, compared
      with respondents without T2DM (n=8686) (4.1 prescriptions, $925 annual medical,
      $118 monthly prescription) (p<0.01). CONCLUSIONS: Increased out-of-pocket medical
      and medication costs in T2DM are due to the use of both antidiabetic agents and
      other medications for treatment of comorbid conditions.

PMID- 20047769
TI  - Seasonal fluctuations of glycated hemoglobin levels in Japanese diabetic
      patients.
AB  - AIMS: We examined whether glycated hemoglobin (HbA(1C)) levels of Japanese
      diabetic patients showed seasonal fluctuations. METHODS: Subjects included 2511
      diabetic patients who regularly visited a single diabetic outpatient clinic for
      10 years. A total of 253,477 HbA(1C) measurements, as well as sex, age, BMI, type
      of diabetes, and mode of therapy were extracted from a hospital-based database.
      For the cross-sectional and longitudinal analyses, average monthly HbA(1C) values
      of subjects and amplitudes of seasonal fluctuations were calculated. For the time
      series analysis, seasonal adjustment factors of each subject were classified as
      complete, incomplete, or no fluctuation. RESULTS: Subjects showed a clear
      seasonal fluctuation of HbA(1C) levels, with highest levels in March (7.69%) and
      lowest levels in August (7.46%; p<0.001). The amplitudes of the seasonal
      fluctuations were associated with the mean HbA(1C) levels. The time-series
      analysis showed that 78.3% of patients had complete or incomplete seasonal
      fluctuations. HbA(1C) levels were highest in winter-spring and lowest in summer
      autumn in most patients; however, some patients showed a reverse pattern.
      CONCLUSIONS: Seasonal fluctuations of HbA(1C) levels were recognized in most of
      the Japanese diabetic patients. Physiological or metabolic factors related to
      temperature may be the main cause of seasonal fluctuations in HbA(1C) levels.

PMID- 20047770
TI  - Start improving the quality of care for people with type 2 diabetes through a
      general practice support program: a cluster randomized trial.
AB  - AIMS: To evaluate the effectiveness of a two-arm quality improvement program
      (QIP) to support general practice with limited tradition in chronic care on type
      2 diabetes patient outcomes. METHODS: During 18 months, we performed a cluster
      randomized trial with randomization of General Practices. The usual QIP (UQIP: 53
      GPs, 918 patients) merged standard interventions including evidence-based
      treatment protocol, annual benchmarking, postgraduate education, case-coaching
      for GPs and patient education. The advanced QIP (AQIP: 67 GPs, 1577 patients)
      introduced additional interventions focussing on intensified follow-up, shared
      care and patient behavioural changes. Main outcomes were HbA1c, systolic blood
      pressure (SBP), and low density lipoprotein cholesterol (LDL-C), analyzed by
      generalized estimating equations and linear mixed models. RESULTS: In UQIP,
      endpoints improved significantly after intervention: HbA1c -0.4%, 95% CI [-0.4; 
      0. 3]; SBP -3mmHg, 95% CI [-4; -1]; LDL-C -13mg/dl, 95% CI [-15; -11]. In AQIP,
      there were no significant additional improvements in outcomes: HbA1c -0.4%, 95%
      CI [-0.4; -0.3]; SBP -4mmHg, 95% CI [-5; -2]; LDL-C -14mg/dl, 95% CI [-15; -11].
      CONCLUSIONS: A multifaceted program merging standard interventions in support of
      general practice induced significant improvements in the quality of diabetes
      care. Intensified follow-up in AQIP with focus on shared care and patient
      behaviour changes did not yield additional benefit.

PMID- 20047771
TI  - Leisure-time physical activity and risk of type 2 diabetes in patients with
      established vascular disease or poorly controlled vascular risk factors.
AB  - AIM: To investigate the effect of leisure-time physical activity on the incidence
      of type 2 diabetes (T2DM) in patients with manifest arterial disease, or poorly
      controlled risk factors. METHODS: We examined 3940 patients with manifest
      arterial disease, hypertension or hyperlipidemia, aged 55.2+/-12.2 years. Leisure
      time physical activity was measured by a questionnaire and metabolic equivalent
      (MET) hours per week (h/wk) were calculated. Incident T2DM was evaluated by a
      specific diabetes questionnaire. RESULTS: Most patients (65%) were physically
      inactive (0METh/wk), 12% were insufficiently physically active (0-10.5METh/wk)
      and 23% were sufficiently physically active (>or=10.5METh/wk). During a mean
      follow-up of 4.7 years, 194 (5%) incident cases of T2DM occurred. Sufficiently
      physically active patients had a lower incidence of diabetes (hazard ratio (HR)
      0.55, 95% confidence interval (CI) 0.37-0.83). Patients who were physically
      active and not-obese (BMI<30kg/m(2)) were at the lowest risk for developing T2DM
      (HR 0.18, 95% CI 0.12-0.28) compared with patients who were physically inactive
      and obese. CONCLUSIONS: Leisure-time physical activity is associated with a
      decreased risk of T2DM in patients with manifest arterial disease, or poorly
      controlled risk factors. The combination of physical activity and non-obesity is
      associated with an even lower risk of the development of type 2 diabetes than the
      sum of their independent, protective effect.

PMID- 20047772
TI  - Transcription factor, SP1, in epiretinal membranes of patients with proliferative
      diabetic retinopathy.
AB  - SP1 mRNA was highly expressed in the epiretinal membranes of proliferative
      diabetic retinopathy (PDR), and the SP1 protein was mainly co-localized with
      vascular endothelial growth factor. SP1 might play an important role in the
      angiogenesis of PDR by regulating the promoter activity and expression of genes
      encoding angiogenesis-related factors.

PMID- 20047773
TI  - Physician and patient characteristics associated with prescriptions and costs of
      drugs in the Lazio region of Italy.
AB  - OBJECTIVE: Prescribing medications is one of the most important therapeutic
      activities of a general practitioner (GP) and the quality of such practices is a
      relevant issue. Our objective was to use regional administrative databases to
      assess the following: (a) the prevalence of prescription drug use by patient age
      and gender, (b) different GPs' prescription volumes and average drug expenditure,
      and (c) how GPs' socio-demographic variables may be considered as predictive
      factors in their prescribing practices. METHODS: An observational cross-sectional
      study was carried out in the primary care setting (GPs and paediatricians only)
      on drug utilization in the period 1st January-31st December 2007. Poisson
      regression models were run to estimate the incidence rate ratio (IRR) of
      prevalence adjusted by patients' age. Linear regression models (for GPs and
      paediatricians separately) were performed to test the possible association
      between average drug expenditure and physicians' characteristics. RESULTS: The
      overall prevalence of drug utilization was approximately 65% of the total
      population and this finding is coherent with other studies. Age was a predictive
      determinant of average drug expenditure that was significantly higher for the
      elderly. Younger physicians were more likely to prescribe medications,
      independent of the presence of any chronic condition in their beneficiaries.
      Female GPs, those practicing in a group and those practicing in central Rome had
      a higher average drug expenditure. Results for paediatricians showed that there
      was a very strong geographical effect that influenced average expenditure.
      CONCLUSIONS: Prescribing decisions are subject to a myriad of external factors.
      The present study shows how physicians' characteristics might affect drug
      prescription in terms of prevalence of use, costs and consumption. Using regional
      administrative databases it has been possible to analyse the association between
      doctors' prescribing habits, their socio-demographic factors and characteristics
      of their catchments areas. However, the variability in age groups in terms of
      prevalence, consumption and expenditure suggests that a sophisticated method of
      analysis will be needed in order to implement strategies and interventions able
      to optimise resource use in the health care sector.

PMID- 20047774
TI  - AIBench: a rapid application development framework for translational research in
      biomedicine.
AB  - Applied research in both biomedical discovery and translational medicine today
      often requires the rapid development of fully featured applications containing
      both advanced and specific functionalities, for real use in practice. In this
      context, new tools are demanded that allow for efficient generation, deployment
      and reutilization of such biomedical applications as well as their associated
      functionalities. In this context this paper presents AIBench, an open-source Java
      desktop application framework for scientific software development with the goal
      of providing support to both fundamental and applied research in the domain of
      translational biomedicine. AIBench incorporates a powerful plug-in engine, a
      flexible scripting platform and takes advantage of Java annotations, reflection
      and various design principles in order to make it easy to use, lightweight and
      non-intrusive. By following a basic input-processing-output life cycle, it is
      possible to fully develop multiplatform applications using only three types of
      concepts: operations, data-types and views. The framework automatically provides
      functionalities that are present in a typical scientific application including
      user parameter definition, logging facilities, multi-threading execution,
      experiment repeatability and user interface workflow management, among others.
      The proposed framework architecture defines a reusable component model which also
      allows assembling new applications by the reuse of libraries from past projects
      or third-party software.

PMID- 20047776
TI  - Dark exposure of petunia cuttings strongly improves adventitious root formation
      and enhances carbohydrate availability during rooting in the light.
AB  - The effect of temporary dark exposure on adventitious root formation (ARF) in
      Petuniaxhybrida 'Mitchell' cuttings was investigated. Histological and metabolic
      changes in the cuttings during the dark treatment and subsequent rooting in the
      light were recorded. Excised cuttings were exposed to the dark for seven days at
      10 degrees C followed by a nine-day rooting period in perlite or were rooted
      immediately for 16 days in a climate chamber at 22/20 degrees C (day/night) and a
      photosynthetic photon flux density (PPFD) of 100micromolm(-2)s(-1). Dark exposure
      prior to rooting increased, accelerated and synchronized ARF. The rooting period
      was reduced from 16 days (non-treated cuttings) to 9 days (treated cuttings).
      Under optimum conditions, despite the reduced rooting period, dark-exposed
      cuttings produced a higher number and length of roots than non-treated cuttings.
      An increase in temperature to 20 degrees C during the dark treatment or extending
      the cold dark exposure to 14 days caused a similar enhancement of root
      development compared to non-treated cuttings. Root meristem formation had already
      started during the dark treatment and was enhanced during the subsequent rooting
      period. Levels of soluble sugars (glucose, fructose and sucrose) and starch in
      leaf and basal stem tissues significantly decreased during the seven days of dark
      exposure. This depletion was, however, compensated during rooting after 6 and 24h
      for soluble sugars in leaves and the basal stem, respectively, whereas the
      sucrose level in the basal stem was already increased at 6h. The association of
      higher carbohydrate levels with improved rooting in previously dark-exposed
      versus non-treated cuttings indicates that increased post-darkness carbohydrate
      availability and allocation towards the stem base contribute to ARF under the
      influence of dark treatment and provide energy for cell growth subject to a
      rising sink intensity in the base of the cutting.

PMID- 20047775
TI  - The role of phosphorylatable serine residues in the DNA-binding domain of
      Arabidopsis bZIP transcription factors.
AB  - Reversible phosphorylation plays a crucial role in regulating the activity of
      enzymes and other proteins in all living organisms. Particularly, the
      phosphorylation of transcription factors can modulate their capability to
      regulate downstream target genes. In plants, basic domain-containing leucine
      zipper (bZIP) transcription factors have an important function in the regulation
      of many developmental processes and adaptive responses to the environment. By a
      comprehensive sequence analysis, we identified a set of highly conserved,
      potentially phospho-accepting serines within the DNA-binding domain of plant
      bZIPs. Structural modelling revealed that these serines are in physical contact
      with the DNA and predicts that their phosphorylation will have a major influence
      on the DNA-binding activity of plant bZIPs. In support of this, we show, by means
      of a quantitative in vitro binding assay, that phosphorylation-mimicking
      substitutions of some of these serines strongly interfere with the DNA binding of
      two prototypical Arabidopsis bZIPs, namely AtZIP63 and HY5. Our data suggest that
      the identified serines could serve as in vivo targets for kinases and
      phosphatases, allowing the fine-tuning of bZIP factor activity at the DNA-protein
      interaction level.

PMID- 20047777
TI  - Synthesis and antimicrobial studies on novel sulfonamides containing 4
      azidomethyl coumarin.
AB  - A series of new and novel coumarin-6-sulfonamides with a free C4-azidomethyl
      group have been synthesized as antimicrobials in three steps starting from 7
      methyl-4-bromomethylcoumarin 1. The reaction of 1 with chlorosulfonic acid was
      found to yield the corresponding 6-sulfonylchloride 2, which when treated with
      sodium azide led to intermediate 3. The title sulfonamides 5a-y were obtained
      from the reaction of 3 with various aromatic amines 4 in refluxing benzene. The
      chemical structures of the compounds were elucidated by IR, NMR and LC-MS
      spectral data. All the synthesized compounds have been screened for their in
      vitro anti-bacterial and anti-fungal activities. Some of the compounds have been
      found to be active against both bacterial species at a concentration of 1
      microg/mL.

PMID- 20047778
TI  - An expeditious synthesis and anticancer activity of novel 4-(3'-indolyl)oxazoles.
AB  - A series of 4-(3'-indolyl)oxazole congeners have been synthesized and studied for
      their cytotoxicity against six cancer cell lines. Reaction of 3-acetyl-1'
      benzenesulfonylindole with [hydroxy(tosyloxy)iodo]benzene afforded pure 3
      tosyloxyacetyl-1'-benzenesulfonylindole. Microwave-accelerated neat reaction of 3
      tosyloxyacetyl-1-benzenesulfonylindole with amides resulted in the exclusive
      formation of 4-(1'-benzenesulfonylindol-3'-yl)-2-substituted oxazoles (4) in very
      good yield. Treatment of 4 with aqueous sodium hydroxide under refluxing
      conditions afforded pure 4-(3'-indolyl)-2-substituted oxazoles (5) in excellent
      yield. The 4-(3'-indolyl)oxazoles 5d and 11 were found to be most cytotoxic and
      selective against various cancer cell lines. Compounds 5g, 5j and 5l showed
      moderate anticancer activity.

PMID- 20047779
TI  - Discovery of benzhydrylpiperazine derivatives as CB1 receptor inverse agonists
      via privileged structure-based approach.
AB  - The present study describes the identification via privileged structure-based
      approach of the benzhydrylpiperazine moiety as a potential scaffold to develop
      novel CB(1) receptor modulators. Efficient structural optimization of the initial
      four hit compounds led to a high quality lead series, represented by compound 6c.
      Compound 6c is a highly potent and selective CB(1) receptor inverse agonist that
      is able to reduce body weight in diet-induced obese Sprague-Dawley rats. The
      preparation of privileged structure-based library, the progression from hit to
      lead, the structure-activity relationships in the lead series and in vitro and in
      vivo activity of compound 6c are discussed.

PMID- 20047780
TI  - Vetiver grass is capable of removing TNT from soil in the presence of urea.
AB  - The high affinity of vetiver grass for 2,4,6 trinitrotoluene (TNT) and the
      catalytic effectiveness of urea in enhancing plant uptake of TNT in hydroponic
      media we earlier demonstrated were further illustrated in this soil-pot
      experiment. Complete removal of TNT in urea-treated soil was accomplished by
      vetiver at the low initial soil-TNT concentration (40 mg kg(-1)), masking the
      effect of urea. Doubling the initial TNT concentration (80 mg kg(-1))
      significantly (p<0.002) increased TNT removal by vetiver, in the presence of
      urea. Without vetiver grass, no significant (p=0.475) change in the soil-TNT
      concentrations was observed over a period of 48 days, suggesting that natural
      attenuation of soil TNT could not explain the documented TNT disappearance from
      soil.

PMID- 20047781
TI  - Distribution of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo
      p-dioxins and dibenzofurans (PBDD/Fs) in municipal solid waste incinerators.
AB  - The stack flue gases and the ashes in different units of two municipal solid
      waste incinerators (MSWIs) are sampled to investigate the characteristics of
      polybrominated diphenyl ethers (PBDEs), polybrominated dibenzo-p-dioxins and
      dibenzofurans (PBDD/Fs), and polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs). Bottom ashes (BA) exhibited much higher PBDD/F (8.11-52.2 pg TEQ/g)
      and PBDE contents (20.4-186 ng/g) than those of fly ashes (0.0932-2.02 pg TEQ/g
      and 0.332-25.5 ng/g), revealing that the PBDD/Fs and PBDEs in the feeding waste
      may not be completely destroyed. The PBDE concentrations/contents in the stack
      flue gases (26.1-109 ng/Nm(3)) and in the BA (20.4-186 ng/g) of the MSWIs could
      reach three orders higher than those in the atmosphere and reference soils. PBDE
      contributions to the environment from the stack flue gases or the reutilization
      of BA of MSWIs should not be ignored from the developing PBDE inventory.

PMID- 20047782
TI  - Lead (Pb) isotopic fingerprinting and its applications in lead pollution studies
      in China: a review.
AB  - As the most widely scattered toxic metal in the world, the sources of lead (Pb)
      observed in contamination investigation are often difficult to identify. This
      review presents an overview of the principles, analysis, and applications of Pb
      isotopic fingerprinting in tracing the origins and transport pathways of Pb in
      the environment. It also summarizes the history and current status of lead
      pollution in China, and illustrates the power of Pb isotopic fingerprinting with
      examples of its recent applications in investigating the effectiveness of leaded
      gasoline phase-out on atmospheric lead pollution, and the sources of Pb found in
      various environmental media (plants, sediments, and aquatic organisms) in China.
      The limitations of Pb isotopic fingerprinting technique are discussed and a
      perspective on its development is also presented. Further methodological
      developments and more widespread instrument availability are expected to make
      isotopic fingerprinting one of the key tools in lead pollution investigation.

PMID- 20047784
TI  - Impact of chemical, biological, radiation, and nuclear personal protective
      equipment on the performance of low- and high-dexterity airway and vascular
      access skills.

PMID- 20047783
TI  - Non-completion of personality disorder treatments: a systematic review of
      correlates, consequences, and interventions.
AB  - Non-completion of treatment is a major concern in the provision of therapies for
      people diagnosed with personality disorder, with adverse consequences for
      services, therapists, and other patients. Of even greater concern is that non
      completion of treatment may limit the effectiveness of therapy for individuals.
      Our main aim in this study was to conduct a systematic review of the literature
      on psychosocial treatments for personality disorder to identify factors
      associated with treatment non-completion. Two subsidiary aims were to identify
      studies that reported the relative outcomes of treatment completion and non
      completion, and to identify studies that evaluated psychosocial interventions
      specifically aimed at improving retention in treatment. This information is
      potentially useful in informing selection criteria and directing efforts towards
      improving treatment engagement. Twenty-five empirical studies of factors
      predicting treatment non-completion were identified. The median non-completion
      rate was 37%. A range of patient characteristics, need factors, and environment
      factors were identified as associated with non-completion. However, the studies
      could not be considered homogeneous group for meta-analysis. Four studies
      investigated the effects of treatment non-completion, showing an association with
      adverse outcomes. Only two studies of interventions specifically aimed at
      reducing non-completion were identified. Implications for clinical practice and
      research are discussed.

PMID- 20047785
TI  - Can early serum levels of S100B protein predict the prognosis of patients with
      out-of-hospital cardiac arrest?
AB  - OBJECTIVE: This study aims to know if the level of S100B protein at the
      initiation of cardiopulmonary resuscitation (CPR) and immediately after return of
      spontaneous circulation (ROSC) can predict clinical outcome. MATERIALS AND
      METHODS: A prospective observational study from December 2004 to October 2006 was
      conducted in an urban tertiary hospital emergency department. Clinical
      demographics for out-of-hospital cardiac arrest patients were collected based on
      the Utstein style. Outcomes collected included ROSC for 20min, survival to
      admission, survival and Glasgow Outcome Scale (GOS) at 1 month. S100B protein was
      measured twice before starting CPR (first S100B) and immediately after ROSC
      (second S100B). We investigated the association between S100B protein levels and
      clinical outcomes using a multivariate logistic regression model. RESULTS: A
      total of 151 patients were included (age: 60.2+/-16.8 years, male: 64.2%). Of
      these, 60 (39.7%) had ROSC and 46 (30.5%) survived to admission. After 1 month,
      12 (8.0%) survived and only three patients showed good GOS (>/=4 points). The
      S100B levels were not different for ROSC, survival to admission and 1-month
      survival between survivors and non-survivors (p>0.05, first and second S100 B
      level). For the witnessed out-of-hospital cardiac arrest (OHCA) group (N=87),
      only the first S100B (1.22+/-0.85mugl(-1) vs. 3.91+/-4.25mugl(-1), p<0.001)
      showed significant difference for 1-month survival between survivors and non
      survivors. The first S100B showed significant association with survival to
      emergency department (ED) but not 1-month survival (adjusted odds ratio
      (OR)=0.905, 95% confidence interval=0.821-0.998). CONCLUSION: Higher levels of
      S100B at start of CPR were significantly associated with lower survival to
      admission, and not for 1-month survival.

PMID- 20047786
TI  - Pre-resuscitation factors associated with mortality in 49,130 cases of in
      hospital cardiac arrest: a report from the National Registry for Cardiopulmonary
      Resuscitation.
AB  - AIM: To evaluate key pre-arrest factors and their collective ability to predict
      post-cardiopulmonary arrest mortality. CPR is often initiated indiscriminately
      after in-hospital cardiopulmonary arrest. Improved understanding of pre-arrest
      factors associated with mortality may inform advance care planning. METHODS: A
      cohort of 49,130 adults who experienced pulseless cardiopulmonary arrest from
      January 2000 to September 2004 was obtained from 366 US hospitals participating
      in the National Registry for Cardiopulmonary Resuscitation (NRCPR). Logistic
      regression with bootstrapping was used to model in-hospital mortality, which
      included those discharged in unfavorable and severely worsened neurologic state
      (Cerebral Performance Category >/=3). RESULTS: Overall in-hospital mortality was
      84.1%. Advanced age, black race, non-cardiac, non-surgical illness category, pre
      existing malignancy, acute stroke, trauma, septicemia, hepatic insufficiency,
      general floor or Emergency Department location, and pre-arrest use of
      vasopressors or assisted/mechanical ventilation were independently predictive of
      in-hospital mortality. Retained peri-arrest factors including cardiac monitoring,
      and shockable initial pulseless rhythms, were strongly associated with survival.
      The validation model's AUROC curve (0.77) revealed fair performance. CONCLUSIONS:
      Predictive pre-resuscitation factors may supplement patient-specific information
      available at bedside to assist in revising resuscitation plans during the
      patient's hospitalization.

PMID- 20047787
TI  - Reliability and validity of a scoring instrument for clinical performance during
      Pediatric Advanced Life Support simulation scenarios.
AB  - AIM: To assess the reliability and validity of scoring instruments designed to
      measure clinical performance during simulated resuscitations requiring the use of
      Pediatric Advanced Life Support (PALS) algorithms. METHODS: Pediatric residents
      were invited to participate in an educational trial involving simulated
      resuscitations that employ PALS algorithms. Each subject participated in a
      session comprised of four scenarios (asystole, dysrhythmia, respiratory arrest,
      shock). Video-recorded sessions were independently reviewed and scored by four
      raters using instruments designed to measure performance in terms of timing,
      sequence, and quality. Validity was assessed by two-factor analysis of variance
      with postgraduate year (PGY-1 versus PGY-2) as an independent variable.
      Reliability was assessed by calculation of overall interrater reliability (IRR)
      as well as a generalizability study to estimate variance components of individual
      measurement facets (scenarios, raters) and associated interactions. RESULTS: 20
      subjects were scored by four raters. Based on a two-factor ANOVA, PGY-2s
      outperformed PGY-1s (p<0.05); significant differences in difficulty existed
      between the four scenarios, with dysrhythmia scores being the lowest. Overall IRR
      was high (0.81) and most variance could be attributed to subject (17%), scenario
      (13%), and the interaction between subject and scenario (52%); variance
      attributable to rater was minimal (1.4%). CONCLUSIONS: The instruments assessed
      in this study measure clinical performance during PALS scenarios in a reliable
      and valid manner. Measurement error could be minimized further through the use of
      additional scenarios but additional raters, for a given scenario, would not
      improve reliability. Further studies should assess validity of measurement with
      respect to actual clinical performance during resuscitations.

PMID- 20047788
TI  - Inherited antithrombin deficiency and pregnancy: maternal and fetal outcomes.
AB  - OBJECTIVE: To describe the outcome of pregnancy in women with inherited
      antithrombin (AT) deficiency. STUDY DESIGN: A descriptive retrospective study was
      performed. Medical records were reviewed in order to collect data about maternal
      thrombotic complications and pregnancy outcomes. All women with known inherited
      AT deficiency and at least one pregnancy looked after at the Vall d'Hebron
      University Hospital were included. Relatives with known AT deficiency but no
      pregnancies looked after in our institution were excluded. Eighteen pregnancies
      were registered among nine AT-deficient women during 1991-2005. This cohort
      included women without antithrombotic treatment because AT deficiency was not
      known at the time of their pregnancies. RESULTS: In 12 pregnancies (66.7%)
      anticoagulant therapy with low-molecular weight heparin was given, while not in
      the other six (33.3%) because AT deficiency was not known at this time. Three
      episodes of venous thromboembolism were recorded (16.7%). Among all pregnancies
      10 suffered an adverse outcome (55.6%), including miscarriage (11.1%), stillbirth
      (11.1%), intrauterine growth restriction (33.3%), placental abruption (6.7%),
      preeclampsia (6.7%) and intrapartum fetal distress (23.1%). No relation between
      AT activity and pregnancy complications was found. A lower incidence of pregnancy
      complications was observed among women with antithrombotic treatment.
      CONCLUSIONS: Inherited antithrombin deficiency is associated with a high risk of
      venous thromboembolism during pregnancy and the puerperium. We also observed a
      high incidence of poor pregnancy outcome among AT-deficient women.

PMID- 20047789
TI  - Re: Guido Dalbagni, Kinjal Vora, Matthew Kaag, et al. Clinical outcome in a
      contemporary series of restaged patients with clinical T1 bladder cancer. Eur
      Urol 2009;56:903-10.

PMID- 20047790
TI  - Basilar artery occlusive disease in stroke survivors in a multiethnic population.
AB  - OBJECTIVES: To describe clinical, radiological findings, and outcome in a
      multiethnic population of stroke survivors with basilar artery occlusive disease
      (BAOC). METHODS: Forty patients with infarcts in the basilar artery (BA)
      territory, alive 30 days after the ictus, participated in the study. BA stenosis
      (>50%) or occlusion was shown by magnetic resonance or digital subtraction
      angiography in all patients. Demographical, clinical and radiological
      characteristics were described. Modified Rankin Scale (MRS) scores at 30 days and
      6 months after the ischemic event were evaluated. Association between
      demographical, clinical, radiological features and outcome were analyzed with Chi
      square and Fisher's exact tests. MRS scores at 30 days and 6 months were compared
      with the Wilcoxon test. RESULTS: Sixty percent of the patients were men, and 33%
      were Afro-Brazilian. Mean age was 55.8+/-12.9 years. Most (90%) had multiple
      vascular risk factors. Stroke was preceded by TIA in 48% of the patients, and 80%
      had a history of arterial hypertension. The most common neurological symptom was
      vertigo/dizziness (60%) and the sign, hemiparesis (60%). Most of the infarcts
      were located in the pons (85%) and the BA middle third was the most frequently
      affected segment (33%). BA occlusion occurred in 58% of the patients. More severe
      vascular occlusive lesions were present in Whites (p=0.002) and in patients with
      involvement of the middle third of the BA (p=0.021). Large-artery atherosclerosis
      was the most common stroke etiology (88%) and was more frequent in older patients
      (p<0.001). Most patients were treated with anticoagulation. MRS scores improved
      significantly at 6 months (p<0.001); at this time, 78% of the patients had MRS
      scores between 0 and 2. CONCLUSIONS: We observed different results compared with
      other series: greater proportion of Afro-descendents, higher frequency of
      atherosclerosis and BA occlusion. Rates of preceding TIAs and good outcome at 6
      months were similar to previously published data. These results represent a step
      forward towards understanding BAOC in a multiethnic context.

PMID- 20047791
TI  - The detoxification of lead in Sedum alfredii H. is not related to phytochelatins
      but the glutathione.
AB  - Two ecotypes of S. alfredii [Pb accumulating (AE) and Pb non-accumulating (NAE)]
      differing in their ability in accumulating Pb were exposed to different Pb levels
      to evaluate the effects on plant length, photosynthetic pigments, antioxidant
      enzymes (SOD and APX), cysteine, non-protein thiols (NP-SH), phytochelatins (PCs)
      and glutathione (GSH) vis-a-vis Pb accumulation. Both ecotypes showed significant
      Pb accumulation in roots, however only the AE showed significant Pb accumulation
      in shoots. We found that both AE and NAE of S. alfredii-induced biosynthesis of
      GSH rather than phytochelatins in their tissue upon addition of even high Pb
      levels (200 microM). Root and shoot length were mostly affected in both ecotypes
      after addition of higher Pb concentrations and on longer durations, however
      photosynthetic pigments did not alter upon addition of any Pb treatment. Both
      superoxide dismutase (SOD) and ascorbate peroxidase (APX) activities of AE were
      higher than NAE. The levels of cysteine and NP-SH were also higher in AE than in
      NAE. Hence, the characteristic Pb accumulation of ecotypes differed presumably in
      relation to their capacity for detoxification of Pb. These results suggest that
      enzymatic and non-enzymatic antioxidants play a key role in the detoxification of
      Pb-induced toxic effects in Sedum alfredii. This plant can be used as an
      indicator species for Pb contamination.

PMID- 20047792
TI  - Membrane filtration technologies applied to municipal secondary effluents for
      potential reuse.
AB  - Four UF membranes (denoted GH, GK, PT and PW with MWCO of 1000, 2000, 5000 and
      20,000Da, respectively) and four NF membranes (denoted DL, CK, DK and HL, with an
      approximate MWCO of 150-300Da in all cases) were used for the filtration of an
      effluent generated in a municipal wastewater plant after a secondary treatment.
      The influence of the most important operating variables (nature and MWCO of the
      membranes, transmembrane pressure, tangential velocity, and temperature) on the
      permeate flux was widely discussed, and the resistances to the permeate flux were
      determined following the resistances in series model. Rejection coefficients for
      parameters that measure the global pollutant content of the effluent (chemical
      oxygen demand, total organic carbon, absorbance at 254nm, turbidity, total
      nitrogen and total phosphorus) were also evaluated, and the results revealed that
      both UF and NF are feasible options for the treatment of this effluent, yielding
      a permeate stream that can be reused in several applications. Finally, 28
      pharmaceutical compounds were initially detected in this effluent, and their
      respective rejection coefficients were determined, with eliminations higher than
      75% in the case of NF with the HL membrane. Therefore, it is concluded that NF is
      an excellent option for the removal of toxic pharmaceuticals in municipal
      wastewaters.

PMID- 20047793
TI  - Removal of Zn2+ from aqueous single metal solutions and electroplating wastewater
      with wood sawdust and sugarcane bagasse modified with EDTA dianhydride (EDTAD).
AB  - This work describes the preparation of a new chelating material derived from wood
      sawdust, Manilkara sp., and not only the use of a new support, but also a
      chemically modified sugarcane bagasse synthesized in our previous work to remove
      Zn(2+) from aqueous solutions and electroplating wastewater. The first part
      describes the chemical modification of wood sawdust and sugarcane bagasse using
      ethylenediaminetetraacetic dianhydride (EDTAD) as modifying agent in order to
      introduce carboxylic acid and amine functional groups into these materials. The
      obtained materials such as the modified sugarcane bagasse, EB, and modified wood
      sawdust, ES were then characterized by infrared spectroscopy (IR) and CHN. The
      second part evaluates the adsorption capacity of Zn(2+) by EB and ES from aqueous
      single metal solutions and real electroplating wastewater, which concentration
      was determined through direct titration with EDTA and inductively coupled plasma
      (ICP-OES). Adsorption isotherms were developed using Langmuir model. Zn(2+)
      adsorption capacities were found to be 80 mg/g for ES and 105 mg/g for EB whereas
      for the industrial wastewater these values were found to be 47 mg/g for ES and 45
      mg/g for EB. Zn(2+) adsorption in the wastewater was found to be lower than in
      Zn(2+) spiked solution due to the competition between other cations and/or
      interference of other ions, mainly Ca(2+) and Cl(-) that were present in the
      wastewater.

PMID- 20047794
TI  - Total oxidation of toluene over calcined trimetallic hydrotalcites type
      catalysts.
AB  - Two trimetallic ZnCuAl and MnCuAl hydrotalcites have been successfully
      synthesized by a co-precipitation method. The manganese based material was
      identified as a new hydrotalcite phase. Both lamellar precursors were calcined at
      450 and 600 degrees C and the resulting catalysts were tested on reaction of
      total oxidation of toluene. The solids were characterized by X-ray diffraction,
      thermal analysis, atomic absorption spectroscopy, Fourier transformed infrared
      spectroscopy, N(2) adsorption and H(2) temperature-programmed reduction. It was
      found that ZnCuAl materials are composed of copper and zinc oxides supported on
      alumina; while MnCuAl ones comprise basically spinel phases, which were not
      completely identified. The catalytic behavior of the calcined samples showed that
      Mn hydrotalcite calcined at 450 degrees C exhibited the best catalytic
      performance that corresponds to 100% toluene conversion into CO(2) at about 300
      degrees C.

PMID- 20047795
TI  - Contrasting effects of elevated CO2 on Cu and Cd uptake by different rice
      varieties grown on contaminated soils with two levels of metals: implication for
      phytoextraction and food safety.
AB  - A pot experiment in six open-top chambers with two levels of CO(2) and two multi
      metal contaminated soils was conducted to investigate combined effects of
      elevated CO(2) levels and metals (Cu and Cd) on rice. Elevated CO(2)
      significantly increased the total dry weight biomass of six Chinese rice by 20
      108 and 32-142% for low and high levels of contaminated soils, respectively. We
      observed dilution/little varied phenomena in grain Cu concentration in six rice
      varieties grown on both contaminated soils under elevated CO(2). We found
      significantly higher Cd concentrations in the parts of three rice varieties under
      elevated CO(2), but lower levels for the others. Two major conclusions can be
      drawn from our study: (1) rice varieties with significantly increased biomass and
      metal uptake under elevated CO(2) exhibit greater potential for phytoextraction
      and (2) given expected global increases in CO(2) concentration, CO(2)-induced
      accumulation of metals in rice might be a component contributing to the potential
      health risk in the future, with Cd being a more important threat to human health
      than Cu.

PMID- 20047796
TI  - Oxidation products of sulfamethoxazole in ozonated secondary effluent.
AB  - In this study the antibiotic sulfamethoxazole (SMX) was subjected to ozone
      treatment. Solutions of 60 mg/L and 100 microg/L SMX in pure water and secondary
      municipal effluent were treated. The removal profile of SMX and its oxidation
      products was monitored as a function of transferred ozone dose in both matrices.
      No difference was observed in the ozone dose required for the concentration of
      SMX to fall below the limit of detection in pure water and wastewater. New peaks
      with the same retention times were obtained on the HPLC chromatograms for all
      conditions studied. Solutions with an initial concentration of 60 mg/L required
      83 mg/L of ozone to fall below the limit of detection and eight oxidation
      products were detected. Solutions with an initial concentration of 100 microg/L
      required 14 mg/L of ozone and only four oxidation products were detected. The
      four peaks obtained during experiments at low concentration were observed at the
      same retention times as four of the peaks obtained in higher concentration
      samples. In ozonated wastewater these products were identified as: 4-aminobenzene
      sulfonamide, N-(3-phenylpropyl)-acetamide, 2-methyl-benzoxazole and phenol. In
      addition, methanol, ethanol, acetic acid, methyl acetate and ethyl acetate were
      identified in the higher concentration samples.

PMID- 20047797
TI  - Encapsulating fly ash and acidic process waste water in brick structure.
AB  - Fly ash contains metals such as cadmium, iron, lead, aluminum and zinc in its
      structure in appreciable amounts. These metals can leach out into surface and
      ground waters if fly ash is not properly disposed of. A similar problem also
      exists for acidic process waste waters discharged by numerous industries. The
      purpose of this study was to utilize such wastes as additives in the production
      of construction quality bricks for the purpose of waste elimination. The bricks
      produced were subjected to flexural strength and water retention capacity tests
      along with heavy metal leaching experiments in order to determine the
      applicability of the procedure and the best possible recipes. This paper
      summarizes the results obtained in these tests along with the possible mechanisms
      involved in stabilizing the two wastes in the brick structure.

PMID- 20047798
TI  - Nicotinic acetylcholine receptor but not acetylcholinesterase plays an important
      role in nicotine-related periodontitis.

PMID- 20047799
TI  - The light theory of mental illness: is there a relationship between sunspot
      number and mental disorders?

PMID- 20047800
TI  - A prospective phase III randomized trial of hypofractionation versus conventional
      fractionation in patients with high-risk prostate cancer.
AB  - PURPOSE: To compare the toxicity and efficacy of hypofractionated (62 Gy/20
      fractions/5 weeks, 4 fractions per week) vs. conventional fractionation
      radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate
      cancer. METHODS AND MATERIALS: From January 2003 to December 2007, 168 patients
      were randomized to receive either hypofractionated or conventional fractionated
      schedules of three-dimensional conformal radiotherapy to the prostate and seminal
      vesicles. All patients received a 9-month course of total androgen deprivation
      (TAD), and radiotherapy started 2 months thereafter. RESULTS: The median (range)
      follow-up was 32 (8-66) and 35 (7-64) months in the hypofractionation and
      conventional fractionation arms, respectively. No difference was found for late
      toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and
      16% for gastrointestinal and 14% and 11% for genitourinary in the
      hypofractionation and conventional fractionation groups, respectively. The 3-year
      freedom from biochemical failure (FFBF) rates were 87% and 79% in the
      hypofractionation and conventional fractionation groups, respectively (p =
      0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment
      prostate-specific antigen (iPSA) >20 ng/mL, Gleason score >or=8, or T >or=2c),
      were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The
      multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as
      significant prognostic factors. CONCLUSIONS: Our findings suggest that late
      toxicity is equivalent between the two treatment groups and that the
      hypofractionated schedule used in this trial is superior to the conventional
      fractionation in terms of FFBF.

PMID- 20047801
TI  - Mechanisms underlying the lifetime co-occurrence of tobacco and cannabis use in
      adolescent and young adult twins.
AB  - Using twins assessed during adolescence (Virginia Twin Study of Adolescent
      Behavioral Development: 8-17 years) and followed up in early adulthood (Young
      Adult Follow-Up, 18-27 years), we tested 13 genetically informative models of co
      occurrence, adapted for the inclusion of covariates. Models were fit, in Mx, to
      data at both assessments allowing for a comparison of the mechanisms that
      underlie the lifetime co-occurrence of cannabis and tobacco use in adolescence
      and early adulthood. Both cannabis and tobacco use were influenced by additive
      genetic (38-81%) and non-shared environmental factors with the possible role of
      non-shared environment in the adolescent assessment only. Causation models, where
      liability to use cannabis exerted a causal influence on the liability to use
      tobacco fit the adolescent data best, while the reverse causation model (tobacco
      causes cannabis) fit the early adult data best. Both causation models (cannabis
      to tobacco and tobacco to cannabis) and the correlated liabilities model fit data
      from the adolescent and young adult assessments well. Genetic correlations (0.59
      0.74) were moderate. Therefore, the relationship between cannabis and tobacco use
      is fairly similar during adolescence and early adulthood with reciprocal
      influences across the two psychoactive substances. However, our study could not
      exclude the possibility that 'gateways' and 'reverse gateways', particularly
      within a genetic context, exist, such that predisposition to using one substance
      (cannabis or tobacco) modifies predisposition to using the other. Given the high
      addictive potential of nicotine and the ubiquitous nature of cannabis use, this
      is a public health concern worthy of considerable attention.

PMID- 20047802
TI  - Alcohol misuse and functional impairment in the UK Armed Forces: a population
      based study.
AB  - AIM: To assess whether alcohol misuse was associated with functional impairment
      in the military, and whether an association between any of the measures of
      alcohol misuse and impairment would be explained by psychiatric comorbidity.
      DESIGN: Large cross-sectional study. PARTICIPANTS: 8585 responders of a random
      sample of the regular United Kingdom Armed Forces who completed a questionnaire
      in 2005 were included in the analyses. MEASUREMENTS: Five items of the Short Form
      Questionnaire-36 (SF-36) specifically dealing with functional impairment, and the
      main independent variable was alcohol misuse based on the Alcohol Use Disorders
      Identification Test (AUDIT). FINDINGS: An AUDIT score of > or = 20 was
      consistently associated with impairment with odds ratios between 1.8 (95%
      confidence interval 1.4-2.3) and 3.7 (2.8-4.8). AUDIT scores <20 did not increase
      impairment. Those with a hazardous pattern of drinking (AUDIT score 8-15)
      perceived their functioning to be better than those with an AUDIT score <8. A
      score indicating alcohol dependence was associated with impairment, as, to a
      lesser extent, was alcohol related-harm. Binge drinking was not associated with
      impairment. Half of those with an AUDIT score of > or = 20 had psychological
      comorbidities. CONCLUSION: Perception of impairment was mainly related to those
      with an AUDIT score of > or = 20 or more, those who had an indication of alcohol
      dependence or alcohol related-harm. Intervention on an individual basis should be
      focused on these groups, while effective public health interventions could be
      enhanced for everyone.

PMID- 20047803
TI  - Hepatitis B virus among injecting drug users in Sydney, Australia: prevalence,
      vaccination and knowledge of status.
AB  - BACKGROUND: Despite the availability of an inexpensive and safe vaccine,
      injecting drug users (IDUs) remain at risk of hepatitis B virus (HBV) infection.
      This paper aimed to measure HBV prevalence and vaccination coverage and to assess
      knowledge and concordance of status among IDUs. METHODS: Participants were
      recruited through a primary health care and a drug treatment service and via
      street press in Sydney, Australia. Face-to-face interviews were conducted and
      serology collected. All received $30 for participation. RESULTS: 229 participants
      were recruited, serology was available for 209. Almost all those interviewed had
      been tested for HBV (95%) a median of four (IQR 2-10) times and 61% had been
      tested in the preceding year. Fifty-four percent had evidence of previous
      infection (anti-HBc) and 5% were HBsAg positive. Only 27% had serological
      evidence of vaccination immunity; however, 43% of the sample recalled having
      being told by a health professional that they were vaccinated against HBV.
      Although only three participants reported they did not understand the results of
      their last HBV test, confusion was evident based on self-reported status.
      CONCLUSIONS: Levels of understanding and vaccination coverage were low while
      evidence of prior infection was high among this IDU sample. This is cause for
      concern given the majority of participants were recruited through primary care
      and treatment services. Strategies to bolster vaccination among this group will
      be discussed.

PMID- 20047804
TI  - Antibody to Hsp70 alters response of rabbit preimplantation embryos to
      hyperthermia in vitro.
AB  - The aim of the study was to determine a role of Hsp70 in the response of rabbit
      preimplantation embryos to hyperthermia (HT) in vitro. The embryos were cultured
      at standard (ST, 37.5 degrees C, control) or elevated (HT, 41.5 degrees C)
      temperature for 6h. In half of the embryos from both groups, Hsp70 was blocked by
      the addition of an antibody against Hsp70 into the medium at stages either prior
      to (<or= 8 cell) or after (morula) developmental block (DB). After 6h, the HT
      embryos were post-cultured at 37.5 degrees C for 16-20 h and then evaluated for
      developmental stages, apoptosis (TUNEL, T), cell number and quality of actin
      cytoskeleton. The exposure of embryos to 41.5 degrees C either before or after DB
      did not affect blastocysts (Bl) rate, T-index and embryo cell number. Blockage of
      Hsp70 before DB resulted in no embryos at the Bl stage. From the Hsp70-blocked
      embryos after DB, only 27.6% (ST + anti-Hsp70) and 22.6% (HT + anti-Hsp70) of
      blastocysts were formed, versus 71.4% (ST) and 69.7% (HT) in the non-Hsp70
      blocked group. T-index of Hsp70-blocked embryos prior to DB increased from 6.8%
      (ST) to 28.6% (ST + anti-Hsp70) and from 6.1% (HT) to 29.6% (HT + anti-Hsp70),
      whilst the cell number dropped from 111 +/- 8.1 (ST) to 20.5 +/- 2.42 (ST + anti
      Hsp70) and from 106.8 +/- 8.4 (HT) to 15.4 +/- 1.34 (HT + anti-Hsp70). In
      contrast, in the Hsp70-blocked embryos after DB, neither T-index nor cell number
      was changed comparing to the non-blocked. Damages to the actin cytoskeleton, like
      intracytoplasmic clumps or loss of actin filaments, were only minimally caused by
      hyperthermia but mostly were a result of Hsp70 blockage. In conclusion, the
      embryos at stages before the genome activation (GA) appear to be more sensitive
      to HT. The resistance of pre-GA embryos to HT is related to Hsp70, whilst after
      GA, Hsp70 is probably not the only factor of thermotolerance and the existence of
      an additional protective mechanism(s) is hypothesized.

PMID- 20047805
TI  - Evaluation of shape variability of stallion sperm heads by means of image
      analysis and Fourier descriptors.
AB  - This study quantified and evaluated the variability of sperm head shape for 10
      different stallions. Sperm head shape characteristics including sperm head length
      to width ratio, position of the center of gravity, curvature, and degree of
      roundness were assessed and analysed from images using elliptic Fourier
      descriptors and inverse Fourier transformation. The first four principal
      components accounted for 88.46-92.33% of the total variance and provided a good
      summary of the overall data. In the case of the ejaculate with defective sperm
      heads the components accounted for 97.35-98.21% of variation. The study was able
      to quantitatively confirm that head length to width ratio, which contributed
      48.63-53.48% and 71.30-73.34% to the total variance for normal and defective
      sperm, respectively, was the predominant determining parameter of sperm head
      shape. There were no statistical significant relationships between Fourier
      descriptors and values of sperm concentration and/or motility.

PMID- 20047806
TI  - Collection of trace evidence of explosive residues from the skin in a death due
      to a disguised letter bomb. The synergy between confocal laser scanning
      microscope and inductively coupled plasma atomic emission spectrometer analyses.
AB  - In most deaths caused by explosive, the victim's body becomes a depot for
      fragments of explosive materials, so contributing to the collection of trace
      evidence which may provide clues about the specific type of device used with
      explosion. Improvised explosive devices are used which contain "homemade"
      explosives rather than high explosives because of the relative ease with which
      such components can be procured. Many methods such as chromatography-mass
      spectrometry, scanning electron microscopy, stereomicroscopy, capillary
      electrophoresis are available for use in the identification of explosive residues
      on objects and bomb fragments. Identification and reconstruction of the
      distribution of explosive residues on the decedent's body may give additional
      hints in assessing the position of the victim in relation to the device.
      Traditionally these residues are retrieved by swabbing the body and clothing
      during the early phase, at autopsy. Gas chromatography-mass spectrometry and
      other analytical methods may be used to analyze the material swabbed from the
      victim body. The histological examination of explosive residues on skin samples
      collected during the autopsy may reveal significant details. The information
      about type, quantity and particularly about anatomical distribution of explosive
      residues obtained utilizing confocal laser scanning microscope (CLSM) together
      with inductively coupled plasma atomic emission spectrometer (ICP-AES), may
      provide very significant evidence in the clarification and reconstruction of the
      explosive-related events.

PMID- 20047807
TI  - Forensic analysis of hallucinogenic mushrooms and khat (Catha edulis Forsk) using
      cation-exchange liquid chromatography.
AB  - Hallucinogenic mushrooms (e.g. Psilocybe and Panaeolus species) as well as leaves
      and young shoots of the khat tree (Catha edulis Forsk) are illicit drugs in many
      countries. The exact concentration of the hallucinogenic alkaloids psilocin and
      psilocybin in mushrooms and the sympathomimetic alkaloids cathinone and cathine
      in khat is usually essential for jurisdiction. Facing an increasing number of
      mushroom and khat seizures by German customs authorities, a convenient
      comprehensive quantitative HPLC method based on cation-exchange liquid
      chromatography for these rather "exotic" drugs has been developed which avoids
      time-consuming multi-step sample preparation or chemical derivatization
      procedures. Using this method a number of different hallucinogenic fungi species
      and products that are mainly distributed via the internet have been analysed
      (dried and fresh Psilocybe cubensis Singer as well as P. cubensis collected from
      "grow boxes", Panaeolus cyanescens Berkeley and Broome and so-called "philosopher
      stones" (sclerotia of Psilocybe species)). Highest total amounts of psilocin have
      been detected in dried P. cyanescens reaching up to 3.00+/-0.24 mg per 100 mg.
      The distribution of khat alkaloids in different parts of the khat shoots has been
      studied. High concentrations of cathinone have not only been detected in leaves
      but also in green parts and barks of stalks. Additionally, the sample treatment
      for fresh mushroom and khat samples has been optimised. Highest amounts of
      alkaloids were found when fresh material was freeze-dried.

PMID- 20047808
TI  - Analysis of syndecan-1 and TGF-beta expression in the nasal mucosa and nasal
      polyps.
AB  - OBJECTIVE: Increased understanding of cytokines and their associated
      proteoglycans will contribute to the investigation of the formation of nasal
      polyps. Recently, some studies have suggested that syndecan-1 ectodomains are
      shed in response to low respiratory infection, but no studies regarding nasal and
      paranasal diseases have been reported. Transforming growth factor-beta (TGF-beta)
      is involved in the regulation of nasal polyps, especially in processes crucial to
      the initiation, maintenance, and resolution of inflammatory responses. In the
      nasal mucosa and nasal polyps, we analyzed the expression of syndecan-1, which
      readily promotes infection, and TGF-beta, which plays a role in syndecan-1
      activity. METHODS: Fifteen patients who underwent turbinectomy for the treatment
      of nasal obstruction and seventeen patients with nasal polyps who underwent nasal
      endoscopic sinus surgery were included in this study. The localization of
      syndecan-1 and TGF-beta in the nasal mucosa and nasal polyps was investigated by
      immunohistochemistry, and mRNA transcript levels of syndecan-1 and TGF-beta were
      examined using quantitative real-time PCR. RESULTS: Immunohistochemical staining
      revealed that the expression of syndecan-1 in the nasal mucosa and nasal polyps
      was co-localized with TGF-beta. The mean mRNA expression values for syndecan-1
      and TGF-beta were higher in nasal polyps compared to the nasal mucosa.
      CONCLUSIONS: This is the first report showing expression of syndecan-1 in the
      nasal mucosa and nasal polyps. In nasal polyps, syndecan-1 expression may be
      increased by an unknown mechanism, permitting infection and inducing larger nasal
      polyps. We hypothesize that the accumulation of TGF-beta, which is involved in
      the pathophysiological development of nasal polyps, may result in a change in the
      binding properties of syndecan-1 at inflammatory sites.

PMID- 20047809
TI  - Pretreatment axillary ultrasonography and core biopsy in patients with suspected
      breast cancer: diagnostic accuracy and impact on management.
AB  - Preoperative diagnosis of axillary metastases in breast cancer patients enables
      treatment planning. We aimed to evaluate the diagnostic accuracy of axillary
      ultrasonography and percutaneous biopsy, both alone and in combination, in
      detecting axillary metastases in patients with breast cancer and to assess the
      impact of these techniques on the patients' management. MATERIALS AND METHODS:
      Retrospective study of consecutive patients with suspected breast cancer examined
      between October 2006 and December 2008. The diagnosis of a primary tumor was
      histologically confirmed in all patients. All patients underwent axillary
      ultrasonography and percutaneous core biopsy (14 G) of suspicious lymph nodes. We
      evaluated the morphological characteristics of the lymph nodes by
      ultrasonography. We calculated the diagnostic accuracy of ultrasonography and of
      core biopsy, and assessed the impact of these techniques on patients' treatment.
      RESULTS: We evaluated 675 axillary regions and performed 291 core biopsies of
      axillary lymph nodes in 662 patients. In 650 patients, breast cancer was
      histologically confirmed and in 12 patients malignant tumors in other locations
      were confirmed. The sensitivity and specificity of axillary ultrasonography were
      63.2% and 88.7%, respectively. The absence of a fatty hilum within the lymph node
      was the ultrasonographic finding with the highest positive predictive value for
      malignancy (93.1%). The sensitivity and specificity of axillary core biopsy were
      69.1% and 100%, respectively. Sentinel lymph node biopsy was avoided in 33% of
      initial candidates and immediate breast reconstruction was undertaken in 35.1% of
      the patients with mastectomy and negative axillary core biopsy. CONCLUSIONS:
      Ultrasonography and axillary core biopsy enable adequate pretreatment staging in
      patients with breast cancer and has a positive impact on their management.

PMID- 20047810
TI  - Influence of fluid-attenuated inversion-recovery on stroke apparent diffusion
      coefficient measurements and its clinical application.
AB  - BACKGROUND AND PURPOSE: The application of a fluid-attenuated inversion-recovery
      pulse with a conventional diffusion-weighted MRI sequence (FLAIR DWI) decreases
      the partial volume effects from cerebrospinal fluid on apparent diffusion
      coefficient (ADC) measurements. For this reason, FLAIR DWI may be more useful in
      the evaluation of ischemic stroke, but few studies have looked at the effect of
      FLAIR on ADC measurements in this setting. This study quantitatively compares
      FLAIR DWI and conventional DWI in ischemic stroke of varying ages to assess the
      potential advantages of this technique. METHODS: We respectively analyzed 139 DWI
      studies in patients with ischemic stroke with and without FLAIR at varying time
      points ranging from hyperacute to chronic. ADC values were measured in each
      lesion, as well as in the contralateral normal side. Comparisons were made
      between the ADC values obtained from the DWI sequences with and without FLAIR for
      both the lesion and the normal contralateral side. RESULTS: The ADC measurements
      within the ischemic lesion were very similar on FLAIR DWI and conventional DWI
      for lesions less than 14 days old (p>0.05), but were significantly decreased on
      FLAIR DWI for lesions between 15 and 30 days old and in lesions >31 days old
      (chronic stage) (p<0.01). The contralateral ADC values were all significantly
      decreased on the FLAIR DWI sequence compared with conventional DWI (p<0.01).
      CONCLUSIONS: The application of an inversion pulse does not significantly affect
      the ADC values for early stage ischemic stroke (less than 14 days from symptom
      onset), but results in a more accurate relative ADC measurement by reducing the
      cerebrospinal fluid partial volume effects of the normal contralateral side. In
      addition, combined with the conventional DWI, FLAIR DWI may be helpful in
      determining the age of ischemic lesions.

PMID- 20047811
TI  - CT-analysis of the course of gastrointestinal graft-versus-host disease--patterns
      of involvement.
AB  - OBJECTIVE: To describe the main patterns of distribution of gastrointestinal
      graft-versus-host disease (GVHD) and their chronological course. METHODS: Twenty
      five adult patients (17 men, 8 women, mean age 47 years) were enrolled from
      11/2003 to 11/2007. All patients underwent abdominopelvic CT shortly after onset
      of GVHD-related symptoms and also at follow up. The mean number of CT
      examinations per patient was 3.2+/-2.7 with a total of 81 in a median time period
      of 97 days after HCT. The gastrointestinal tract was divided into 7 segments.
      Gastrointestinal abnormalities were defined as follows: presence of wall
      thickening (>4mm), increased mucosal enhancement, bowel dilatation (>3 cm for the
      small bowel, >8 cm for the colon), fluid-filled loops of the bowel, bowel loop
      separation and double-halo sign. RESULTS: 40% (10/25) of the patients presented a
      classical pattern of evolution of involved segments by GI-GVHD. In these cases,
      especially the small bowel was initially involved showing a retreat with time
      towards the terminal ileum with longer length of stay in this location. 28%
      (7/25) of the patients presented with a nonclassical permanently migratory
      involvement of the GI jumping from one GI segment to another. Other 32% (8/25) of
      our patients revealed a nonclassical persistent, unchanged involvement pattern of
      GI involvement by GVHD at time. CONCLUSION: Contrary to existing reports, our
      data collected in 25 patients diagnosed with GI-GVHD after allogeneic
      hematopoietic stem cell transplantation suggest the presence of three different
      courses (classical, nonclassical migratory and nonclassical persistent) of this
      disorder. Awareness of this knowledge enables more accurate risk stratification.

PMID- 20047812
TI  - A comparison of microwave ablation and bipolar radiofrequency ablation both with
      an internally cooled probe: results in ex vivo and in vivo porcine livers.
AB  - PURPOSE: The purpose of this study was to compare the effectiveness of microwave
      (MW) ablation and radiofrequency (RF) ablation using a single internally cooled
      probe in a hepatic porcine model. MATERIALS AND METHODS: In the ex vivo
      experiment, MW ablations (n=40) were performed with a 2450MHz and 915MHz needle
      antenna, respectively at 60W, 70W power settings. Bipolar RF ablations (n=20)
      were performed with a 3-cm (T30) and 4-cm (T40) active tip needle electrodes,
      respectively at a rated power 30W and 40W according to automatically systematic
      power setting. In the in vivo experiment, the 2450 MHz and 915 MHz MW ablation
      both at 60W and T30 bipolar RF ablation at 30 W were performed (n=30). All of the
      application time were 10 min. Long-axis diameter (Dl), short-axis diameter (Ds),
      ratio of Ds/Dl, the temperature data 5mm from the needle and the time of
      temperature 5mm from the needle rising to 54 degrees C were measured. RESULTS:
      Both in ex vivo and in vivo models, Ds and Dl of 915 MHz MW ablations were
      significantly larger than all the RF ablations (P<0.05); the Ds for all the
      2450MHz MW ablations were significantly larger than that of T30 RF ablations
      (P<0.05). 2450MHz MW and T30 RF ablation tended to produce more elliptical-shaped
      ablation zone. Tissue temperatures 5mm from the needle were considerably higher
      with MW ablation, meanwhile MW ablation achieved significantly faster rate of
      temperature rising to 54 degrees C than RF ablation. For in vivo study after 10
      min of ablation, the Ds and Dl of 2450 MHz MW, 915 MHz MW and Bipolar RF were
      2.35+/-0.75, 2.95+/-0.32, 1.61+/-0.33 and 3.86+/-0.81, 5.79+/-1.03, 3.21+/-0.51,
      respectively. Highest tissue temperatures 5mm from the needle were 80.07+/-12.82
      degrees C, 89.07+/-3.52 degrees C and 65.56+/-15.31 degrees C and the time of
      temperature rising to 54 degrees C were respectively 37.50+/-7.62s, 24.50+/-4.09s
      and 57.29+/-23.24s for three applicators. CONCLUSION: MW ablation may have higher
      potential for complete destruction of liver tumors than RF ablation.

PMID- 20047813
TI  - Diagnostic performance of USPIO-enhanced MRI for lymph-node metastases in
      different body regions: a meta-analysis.
AB  - OBJECTIVES: USPIO (ultrasmall superparamagnetic iron oxide contrast agent) MRI
      was a promising imaging modality in the detection of lymph-node metastases. And
      this meta-analysis is performed to compare the diagnostic accuracy of USPIO
      enhanced MRI with non-enhanced MRI, USPIO-enhanced MRI in various body regions,
      and postcontrast alone for diagnosis of lymph-node metastases. METHODS: A
      comprehensive and systematic search was conducted in PubMed and EMBASE databases.
      After a systematic review of the studies, sensitivity, specificity, the Q* value
      and other measures of accuracy of USPIO-enhanced MRI in the diagnosis of lymph
      node metastases were summarized. The overall test performance was based on
      summary receiver operating characteristic curves. RESULTS: Summary of ROC curve
      analysis for per-lymph-node data shows a pooled sensitivity of 0.90 (95%
      confidential interval [CI]: 0.88-0.91) and overall specificity of 0.96 (95% CI:
      0.95-0.97) for USPIO-enhanced MRI, the Q* value for USPIO-enhanced MRI is 0.9195,
      diagnostic odds ratio (DOR) is 162.28 (95% CI: 91.82-286.81). Non-enhanced MRI
      had less overall sensitivity 0.39 (95% CI: 0.34-0.43) and specificity 0.90 (95%
      CI: 0.89-0.91), respectively, the Q* value for USPIO-enhanced MRI was 0.6321, DOR
      is 5.81 (95% CI: 3.64-9.82). Postcontrast MRI alone had sensitivity 0.85 (95% CI:
      0.81-0.88) and specificity 0.93 (95% CI: 0.91-0.95), respectively, the Q* value
      for USPIO-enhanced MRI was 0.8976, DOR is 76.92 (95% CI: 34.21-172.93). There was
      significant heterogeneity for studies reporting enhanced MRI and non-enhanced
      MRI. CONCLUSIONS: This meta-analysis has shown that USPIO-enhanced MRI offers
      higher diagnostic performance than conventional MRI, and is sensitive and
      specific for the detection of lymph-node metastases. Postcontrast images alone
      can equate diagnostic performance pre- and postcontrast MRI has achieved for
      lymph-node characterization. And the role of USPIO-enhanced MRI in clinical
      practice still needs to be investigated in future studies.

PMID- 20047814
TI  - Molecular detection and phylogenetic analysis of the alkane 1-monooxygenase gene
      from Gordonia spp.
AB  - The alkB gene encodes for alkane 1-monooxygenase, which is a key enzyme
      responsible for the initial oxidation of inactivated alkanes. This functional
      gene can be used as a marker to assess the catabolic potential of bacteria in
      bioremediation. In the present study, a pair of primers was designed based on the
      conserved regions of the AlkB amino acid sequences of Actinobacteria, for
      amplifying the alkB gene from the genus Gordonia (20 Gordonia strains
      representing 13 species). The amplified alkB genes were then sequenced and
      analyzed. In the phylogenetic tree based on the translated AlkB amino acid
      sequences, all the Gordonia segregated clearly from other closely related genera.
      The sequence identity of the alkB gene in Gordonia ranged from 58.8% to 99.1%,
      which showed higher sequence variation at the inter-species level compared with
      other molecular markers, such as the 16S rRNA gene (93.1-99.8%), gyrB gene (77.5
      97.3%) or catA gene (72.4-99.5%). The genetic diversity of four selected loci
      also showed that the alkB gene might have evolved faster than rrn operons, as
      well as the gyrB or catA genes, in Gordonia. All the available actinobacterial
      alkB gene sequences derived from the whole genome shotgun sequencing projects are
      phylogenetically characterized here for the first time, and they exclude the
      possibility of horizontal gene transfer of the alkB gene in these bacterial
      groups.

PMID- 20047815
TI  - The application of fully automated on-line solid phase extraction in bioanalysis.
AB  - This paper describes the application of fully automated on-line solid phase
      extraction to the bioanalysis of three example compounds using the Symbiosis
      platform. The on-line assay performance is compared to off-line methodologies for
      the same compounds. The three example compounds possess a variety of
      physicochemical properties and different extraction modes were applied in off
      line methods. These methods were developed through optimisation of solid phase or
      liquid-liquid extraction and chromatographic separation conditions for each of
      the analytes. Both on-line and off-line methods were evaluated for linearity,
      carryover, imprecision and inaccuracy. Experiments were also performed
      investigating modification of ionisation and selectivity against different
      batches of plasma. On-line and off-line methods were found to be comparable in
      performance. In conclusion, on-line methodology has distinct advantages for the
      analysis of large numbers of samples with a marked reduction in manual operation.

PMID- 20047816
TI  - Evaluating functional decline in patients with Multiple Sclerosis.
AB  - Multiple Sclerosis (MS) is a disease with a wide-ranging impact on functional
      status. The aim of the study was to examine the added value of simultaneously
      evaluating fatigue, personal ADL and handwriting performance as indicators for
      functional decline among patients with MS. Participants were 50 outpatients with
      MS and 26 matched healthy controls. Data collection instruments included a
      disability status scale, the Fatigue Severity Scale (FSS), and the Physical Self
      Maintenance Scale (PSMS). Handwriting performance was evaluated by objective
      computerized measures of the handwriting process (ComPET). Significant
      differences were found between patients with MS and control subjects in their
      fatigue level, their PSMS score and In-air time per stroke while writing. The FSS
      together with specific PSMS items and handwriting measures achieved correct
      classification of 87.7% of the participants. These results are the first step
      towards demonstrating the added value of evaluating body function outcomes
      (fatigue) together with activity performance (handwriting and ADL) to document
      functional decline among patients with MS. These results may contribute to the
      development of practical intervention strategies targeted at improving
      performance abilities among patients with MS.

PMID- 20047817
TI  - Surgical challenges in the treatment of advanced cases of ameloblastoma in the
      developing world: The authors' experience.
AB  - Total mandibulectomy was carried out in 32 patients with extensive oro-facial
      lesions histologically diagnosed as ameloblastoma in four specialist centres in
      south-eastern Nigeria from January 2001 to December 2006. All the patients
      presented at an advanced stage with the whole mandible affected so the treatment
      of choice was total mandibulectomy. The patients gave informed consent for
      surgery. The standard surgical procedure was the same in all cases and was
      performed by the same surgeons. Of the 32 mandibles removed, there were 13 male
      (41%) and 19 female (59%) patients, giving a male-to-female ratio of 1:1.6. Three
      (9%) patients died due to problems relating to anaesthesia while five (16%) had
      postsurgical-related psychosomatic problems. Generally, the postoperative
      recovery was characterized by reduction in the quality of life of these patients
      because immediate jaw reconstruction was not feasible. This article highlights
      the challenges in the surgical management of advanced cases of ameloblastoma in
      the developing world and proposes a middle ground for professional interactions
      and exchange programmes among oral and maxillofacial surgeons across the world to
      assist poorer countries in the management of these advanced cases of oro-facial
      tumours.

PMID- 20047818
TI  - Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and
      resistance.
AB  - Infection due to Acinetobacter baumannii has become a significant challenge to
      modern healthcare systems. The organism shows a formidable capacity to develop
      antimicrobial resistance, yet the clinical impact of A. baumannii infection
      remains unclear. Much is known about the processes involved in multidrug
      resistance, but those underlying the pathogenicity and virulence potential of the
      organism are only beginning to be elucidated. In this article, we provide an
      overview of current knowledge, focusing on mechanisms of pathogenesis, the
      molecular basis of resistance and options for treatment in the absence of novel
      therapeutic agents.

PMID- 20047819
TI  - Deletion of penicillin-binding protein 5 (PBP5) sensitises Escherichia coli cells
      to beta-lactam agents.
AB  - Escherichia coli penicillin-binding protein 5 (PBP5), a dd-carboxypeptidase
      encoded by the dacA gene, plays a key role in the maintenance of cell shape.
      Although PBP5 shares one of the highest copy numbers among the PBPs, it is not
      essential for cell survival. To determine the effect of this redundant PBP on
      beta-lactam antibiotic susceptibility, PBP5 was deleted from O-antigen-negative
      E. coli K-12 (CS109) and O8-antigen-positive E. coli 2443, thus creating strains
      AM15-1 and AG1O5-1, respectively. Compared with the parent strains, both mutants
      were four- to eight-fold more susceptible to all the beta-lactam antibiotics
      tested. Reversion to beta-lactam resistance was observed in the mutants upon
      complementing with cloned PBP5, indicating the involvement of PBP5 in maintaining
      an O-antigen-independent intrinsic beta-lactam resistance in E. coli cells. To
      check whether other dacA homologues were able to substitute this behaviour of E.
      coli PBP5, AG1O5-1 was complemented with its nearest dacA homologues (Salmonella
      enterica serovar Typhimurium LT2, Vibrio cholerae and Haemophilus influenzae).
      All of the cloned homologues were capable of restoring the lost beta-lactam
      resistance in AG1O5-1, either completely or at least partially. Therefore, apart
      from maintaining cell shape, involvement of PBP5 in maintaining intrinsic beta
      lactam resistance is an important physiological observation and we speculate that
      such a strategy of deleting PBP5 may be helpful to introduce beta-lactam
      susceptibility in the laboratory.

PMID- 20047820
TI  - Antimicrobial resistance among clinical isolates from the Chinese Meropenem
      Surveillance Study (CMSS), 2003-2008.
AB  - The Chinese Meropenem Surveillance Study (CMSS) programme was initiated in 2003
      with the aim of monitoring the antimicrobial activity of broad-spectrum agents
      against nosocomial Gram-negative bacilli in China. From 2003 to 2008, a total of
      3892 isolates were collected from 10 teaching hospitals. The minimum inhibitory
      concentrations (MICs) of 11 antimicrobial agents were determined by the agar
      dilution method. During the study period, a marked decrease in the susceptibility
      of Acinetobacter spp. to meropenem and imipenem was noticed, from 94.6% to 60.7%
      and from 92.5% to 62.1%, respectively. However, for Pseudomonas aeruginosa the
      susceptibility was relatively stable, with susceptibility rates of 86.2% to 76.0%
      for meropenem and 74.8% to 70.5% for imipenem. Meropenem and imipenem exhibited
      the highest activities against enterobacterial organisms, with ranges of MIC(90)
      values (MIC for 90% of the organisms) from 0.064mg/L to 0.25mg/L and 0.25 to
      4mg/L, respectively. Except for Acinetobacter spp., the next most active agent
      against the majority of isolates was amikacin, with susceptibility ranging from
      78.8% to 93.3%, followed by piperacillin/tazobactam (73.7% to 98.2%),
      cefoperazone/sulbactam (63.9% to 99.1%), cefepime (67.0% to 95.4%) and
      ceftazidime (54.5% to 93.3%). The percentage of isolates positive for extended
      spectrum beta-lactamases among Escherichia coli, Klebsiella spp. and Proteus
      mirabilis ranged from 50.9% to 66.7%, 25.4% to 42.4% and 8.9% to 24.2%,
      respectively. These CMSS results have demonstrated increasing resistance of
      Acinetobacter spp. to carbapenems, resulting from the spread of highly resistant
      clones. Continued surveillance studies, including CMSS, as well as potent
      measures for controlling the spread of resistant clones are required.

PMID- 20047822
TI  - Radiotherapy demand and activity in England and Australia.

PMID- 20047821
TI  - Fabrication of cationic nanomicelle from chitosan-graft-polycaprolactone as the
      carrier of 7-ethyl-10-hydroxy-camptothecin.
AB  - In this research, amphiphilic brush-like polycations were synthesized, and used
      to fabricate cationic nanomicelle as the carrier of 7-ethyl-10-hydroxy
      camptothecin (SN-38), in order to enhance its cellular uptake, solubility and
      stability in aqueous media. In particular, cationic chitosan-graft
      polycaprolactone (CS-g-PCL) copolymers were synthesized with a facile one-pot
      manner via ring-opening polymerization of epsilon-CL onto the hydroxyl groups of
      CS by using methanesulfonic acid as solvent and catalyst. The formation of CS-g
      PCL nanomicelles was confirmed by fluorescence spectrophotoscopy and particle
      size measurements. It was found that all the nanomicelles showed spherical shapes
      with narrow size distributions. Their sizes ranged from 47 to 113 nm, and the
      zeta potentials ranged from 26.7 to 50.8 mV, depending on the grafting content of
      PCL in CS-g-PCL, suggesting their passive targeting to tumor tissue and
      endocytosis potential. Water-insoluble antitumor drug, SN-38, was easily
      encapsulated into CS-g-PCL nanomicelles by lyophilization method. In comparison
      with bare CS-g-PCL nanomicelles, the corresponding SN-38-loaded nanomicelles
      showed increased particle sizes and a little reduced zeta potentials. With an
      increase of grafting PCL content, the drug encapsulation efficiency (EE) and drug
      loading (DL) of the nanomicelles increased from 64.3 to 84.6% and 6.43 to 8.66%,
      respectively, whereas their accumulative drug release showed a tendency to
      decrease due to the enhanced hydrophobic interaction between hydrophobic drug and
      hydrophobic PCL segments in CS-g-PCL. Also, the CS-g-PCL nanomicelles effectively
      protected the active lactone ring of SN-38 from hydrolysis under physiological
      condition, due to the encapsulation of SN-38 into the hydrophobic cores in the
      nanomicelles. Compared with free SN-38, the SN-38-loaded nanomicelles showed
      essential decreased cytotoxicity against L929 cell line, and bare CS-g-PCL
      nanomicelles almost showed non-toxicity. These results suggested the potential
      utilization of the CS-g-PCL nanomicelles as the carriers of hydrophobic drugs
      with improving the delivery and release properties.

PMID- 20047823
TI  - Spirometry guidelines influence lung function results in a longitudinal study of
      young adults.
AB  - RATIONALE: End of test criteria can influence spirometry results. Epidemiology
      studies initiated before adoption of the 1987 American Thoracic Society (ATS)
      guidelines typically used a 1 or 2 s plateau on the volume-time curve, not a
      minimum test duration of 6 s, to terminate a test. OBJECTIVES: To determine the
      effect of changing guidelines on FEV(1), FVC and FEV(1)/FVC during a longitudinal
      study of young adults. METHODS: Spirometry was performed on participants in the
      Coronary Artery Risk Development in Young Adults (CARDIA) study. Values obtained
      at entry and 2, 5 and 10 years later using accepted procedures were re-evaluated
      using the 2005 ATS-ERS guidelines, which were in effect for the year 20 exam.
      Generalized estimating equations were used to adjust tests with short exhalations
      that were acceptable by then current end of test criteria. RESULTS: The
      percentage of participants at years 0, 2, 5, and 10 with exhalations less than 6
      s but with an acceptable plateau was 33%, 29%, 9%, and 2%, respectively.
      Exhalations less than 6 s occurred more frequently in younger and female
      participants, and were associated with lower FVC and higher FEV(1)/FVC. For short
      exhalations the adjusted FVC was 47 ml and 110 ml higher than the measured FVC
      when 6 and 8 s exhalation times were used. CONCLUSIONS: In longitudinal studies
      of young adults, changing end of test criteria may affect lung function,
      especially among younger and female participants. Determining adjusted values for
      tests with short exhalations may better represent the lung health of
      participants.

PMID- 20047824
TI  - Effect of calcium oxalate on renal cells as revealed by real-time measurement of
      extracellular oxidative burst.
AB  - Calcium oxalate is one of the main constituents of kidney stones and has a proved
      deleterious effect on renal cells that is mediated by oxidative stress. However,
      the subcellular source of this oxidative stress, and whether it is extending to
      the extracellular space or not, is still disputed. Therefore, an electrochemical
      superoxide biosensor was constructed, positioned above A6 renal cells, and used
      to measure in real-time the extracellular oxidative burst following addition of
      calcium oxalate crystals. It was observed that A6 cells do secrete superoxide
      into their extracellular space in few minutes after encountering calcium oxalate
      crystals. The amount of released superoxide peaks at about 20 min. Superoxide is
      cleared away from the extracellular space after approximately 3h. Superoxide
      secretion depends on the presence of superoxide-scavenging enzyme superoxide
      dismutase, the age of the cells, the amount of calcium oxalate crystals, and the
      temperature. Moreover, the effect of calcium oxalate crystals was mimicked by
      phorbol 12-myristate 13-acetate. The developed sensing system can be a useful
      tool for biologists investigating nephrolithiasis at cellular level.

PMID- 20047825
TI  - Electrochemical detection of vascular endothelial growth factors (VEGFs) using
      VEGF antibody fragments modified Au NPs/ITO electrode.
AB  - A new electrochemical technique for the detection of vascular endothelial growth
      factors (VEGFs) as a cancer-related biomarker is presented in this paper. Gold
      nanoparticles (Au NPs) were self-assembled onto an indium tin oxide (ITO)
      electrode to prepare a modified sandwich type electrochemical immunoassay
      platform. VEGF antibodies were cleaved into two half-fragments by 2
      mercaptoethylamine-HCl (2-MEA) and the fragments were immobilized onto the Au NP
      substrates by their thiol groups. Through this strategy, randomly oriented
      attachment of antibodies was prevented which frequently occurs in a general use
      of whole antibody and reduces the number of available sites for the attachment of
      target molecules. VEGF target molecules were applied to the immunoelectrodes and
      they combined with the antibody fragments covering the Au NP electrode, forming
      antigen-antibody complexes. Then, ferrocene-tagged antibodies, which release
      electrons under a proper applied potential, were added to the system and they
      combined with the VEGF molecules pre-attached to the antibody fragments. The
      redox current of ferrocene measured by the differential pulse voltammetry (DPV)
      increased almost linearly from 1.27 x 10(-4) to 4.17 x 10(-4)A according to the
      increase in the concentration of the VEGF target molecules from 100 to 600 pg/ml.
      The measured current values represent the concentration of the VEGF since they
      are proportional to the number of ferrocene molecules which is in turn
      proportional to the concentration of VEGF target molecules. Using this modified
      sandwich immunoassay with the Au NP/ITO electrode, VEGFs as low as 100 pg/ml were
      detected with high specificity.

PMID- 20047826
TI  - Integrating carbon nanotubes and lipid bilayer for biosensing.
AB  - Membrane proteins, which are the target of most drugs, are implicated in many
      critical cellular functions such as signal transduction, bioelectricity,
      exocytosis and endocytosis. Therefore, developing techniques to investigate the
      functions of membrane proteins is obviously important. Here, we have developed a
      novel system by integrating artificial lipid bilayer (biomimetic membrane) with
      single-walled carbon nanotube networks (SWNT-net) based field-effect transistor
      (FET), and demonstrated that such hybrid nanoelectronic biosensors can
      specifically and electronically detect the presence and dynamic activities of
      ionophores (specifically, gramicidin and calcimycin) in their native lipid
      environment. This technique can potentially be used to examine other membrane
      proteins (e.g. ligand-gated ion channels, receptors, membrane insertion toxins,
      and antibacterial peptides) for the purposes of biosensing, fundamental studies,
      or high throughput drug screening.

PMID- 20047827
TI  - Electrochemical impedance biosensor with electrode pixels for precise counting of
      CD4+ cells: a microchip for quantitative diagnosis of HIV infection status of
      AIDS patients.
AB  - Oriented for the quantitative diagnosis of HIV infection status of AIDS patients,
      a cell biosensor based on electrochemical impedance spectroscopy has been
      developed for the precise counting of human CD4(+) cells. In this new biosensor,
      the sensing area was composed of densely packed working electrode pixels, each of
      which was comparable to a single CD4(+) cell in size. CD4(+) cells were captured
      on the chemically modified electrode pixels, and detected individually by
      monitoring the interfacial impedance changes on each independent pixel. The
      detection of a single cell was achieved by the "on" and "off" states of electrode
      pixel, depending on the cell capture status. The cell counting was digitalized by
      summing the electrode pixels in the "on" state (captured with a single cell).
      Compared with peer counting methods, the biosensor reported here was featured
      with a small device dimension, a minimal sample consumption, a finest detection
      resolution and a highest counting accuracy.

PMID- 20047828
TI  - Sensitive giant magnetoresistive-based immunoassay for multiplex mycotoxin
      detection.
AB  - Rapid and multiplexed measurement is vital in the detection of food-borne
      pathogens. While highly specific and sensitive, traditional immunochemical assays
      such as enzyme-linked immunosorbent assays (ELISAs) often require expensive read
      out equipment (e.g. fluorescent labels) and lack the capability of multiplex
      detection. By combining the superior specificity of immunoassays with the
      sensitivity and simplicity of magnetic detection, we have developed a novel
      multiplex magnetic nanotag-based detection platform for mycotoxins that functions
      on a sub-picomolar concentration level. Unlike fluorescent labels, magnetic
      nanotags (MNTs) can be detected with inexpensive giant magnetoresistive (GMR)
      sensors such as spin-valve sensors. In the system presented here, each spin-valve
      sensor has an active area of 90 microm x 90 microm, arranged in an 8 x 8 array.
      Sample is added to the antibody-immobilized sensor array prior to the addition of
      the biotinylated detection antibody. The sensor response is recorded in real time
      upon the addition of streptavidin-linked MNTs on the chip. Here we demonstrate
      the simultaneous detection of multiple mycotoxins (aflatoxins B(1), zearalenone
      and HT-2) and show that a detection limit of 50 pg/mL can be achieved.

PMID- 20047829
TI  - Operation of a sequencing batch reactor for cultivating autotrophic nitrifying
      granules.
AB  - The granulation of nitrifying sludge in a sequencing batch reactor (SBR) fed with
      NH(4)(+)-N-laden inorganic wastewater was investigated. After 120-day operation
      spherical and elliptical granules with an average diameter of 0.32 mm were
      observed. The hydrophobicity surface, settling velocity and specific gravity of
      the matured granules increased with the processing of sludge granulation. Spatial
      distribution of bacterial species within the autotrophic granules was analyzed
      with fluorescence in situ hybridization. Both ammonia- and nitrite-oxidizing
      bacteria were observed in the granular sludge. The Michaelis-Menten equation was
      used to describe their NH(4)(+)-N utilization rate, and the kinetic coefficients
      were calculated to be v(m) = 18.0 mg/g-VSS/h and K(m) = 36.7 mg/l. Taking into
      account the NH(4)(+)-N utilization rate and removal efficiency together, an
      NH(4)(+)-N concentration range of 100-250 mg/l was found to be favourable for the
      operation of the SBR to cultivate nitrifying granules.

PMID- 20047830
TI  - Influence of various nitrogenous electron acceptors on the anaerobic sulfide
      oxidation.
AB  - The effect of nitrate and nitrite as electron acceptors on the performance of
      anaerobic sulfide oxidizing process (ASO process) was investigated. For nitrate
      ASO process, the maximum influent nitrogen concentration was lower than that in
      nitrite-ASO process, but the maximum influent sulfur concentration was higher
      than that of nitrite-ASO process. The half saturation values for nitrogen and
      sulfur in both processes were similar. The minimum reaction time taken for
      nitrite and sulfide was relatively shorter than in nitrite-ASO reactor. As
      indicated by sensitivity ratio, activated sludge was more tolerant to sulfide,
      which had no significant differences between two processes; while it was
      relatively more sensitive to nitrite over nitrate. PCR-DGGE fingerprints, Dice
      and Shannon similarity indices and sequencing results all suggested that the
      microbial communities in both reactors were similar. The use of nitrate as an
      electron acceptor may be preferable over nitrite to treat sulfide-rich
      wastewaters.

PMID- 20047831
TI  - Synthesis and antibacterial activity of benzyl-[3-(benzylamino-methyl)
      cyclohexylmethyl]-amine derivatives.
AB  - A series of benzyl-[3-(benzylamino-methyl)-cyclohexylmethyl]-amine derivatives
      with different substitution pattern on the aromatic ring have been prepared and
      evaluated for their antibacterial activity against Gram-positive and Gram
      negative bacterial strains. Most of the compounds exhibit potent activity against
      Pseudomonas aeruginosa and Staphylococcus epidermidis while compounds 6l and 6m
      showed antibacterial activity against all the four bacterial strains with MIC
      values ranging from 0.002 to 0.016 microg/mL and no hemolytic activity up to 512
      microg/mL in mammalian erythrocytes was observed.

PMID- 20047832
TI  - Living with muscular dystrophy: Personal reflections.

PMID- 20047833
TI  - Falls prediction in elderly people: a 1-year prospective study.
AB  - The aim of the present study was to determine whether force plate variables in
      single- and dual-task situations are able to predict the risk of multiple falls
      in a community-dwelling elderly population. Two hundred and seventy elderly
      persons (225 females, 45 males; age, 73+/-7 years) performed balance assessment
      with and without vision. Seven force plate variables were assessed to predict the
      risk of multiple falls; maximum displacement in the anteroposterior and medial
      lateral directions (Max-AP, Max-ML), mean displacement in the medial-lateral
      direction (MML), the root mean square amplitude in anteroposterior and medial
      lateral directions (RMS-AP, RMS-ML), the average speed of displacement (V), and
      the area of the 95th percentile ellipse (AoE). Falls were prospectively recorded
      during the following year. A total of 437 registered falls occurred during
      monitoring period. The force plate variable RMS-ML in the single-task condition
      (odds ratio, 21.8) predicted multiple falls together with the following
      covariables: history of multiple falls (odds ratio, 5.6), use of medications
      (fall-risk medications or multiple medicine use; odds ratio, 2.3), and gender
      (odds ratio, 0.34). Multiple fallers had a narrower stance width than non
      fallers.

PMID- 20047834
TI  - Structural markers for normal oral mucosa and oral sub-mucous fibrosis.
AB  - This article presents a quantitative approach for the characterization of normal
      oral mucosa (NOM) in respect to thickness and textural properties of its entire
      epithelial layer. Histological images of oral mucosa depict that both thickness
      and tissue architecture at cellular and tissue level undergo change, as mucosa
      converts from normal to precancerous or cancerous state. In this study the
      thickness and fractal dimension of the mucosal epithelium of NOM and oral sub
      mucous fibrosis (OSF) condition have been computed using 83 normal and 29 OSF
      images of oral mucosa. The result shows significant delineation between NOM and
      OSF in respect of both the epithelial thickness (in microm) and fractal
      dimensions. This quantitative characterization of oral epithelium will be of
      immense help for oral onco-pathologists and researchers to assess the biological
      nature of normal and diseased (OSF) mucosa with higher accuracy. Moreover,
      further differential applications may enable them to find out newer accurate
      quantitative diagnostic procedures to that of the usual histopathological gold
      standard for the assessment of malignant potentiality.

PMID- 20047835
TI  - Ultrastructural characterization of the spermatozoa of Aethalion reticulatum
      Linnaeus 1767 (Hemiptera: Auchenorrhyncha: Aethalionidae).
AB  - The Hemiptera order is currently divided into four suborders. Among them the
      Auchenorrhyncha suborder is considered to be paraphyletic. Morphology of insect
      spermatozoa has provided promising characteristics that can be used for
      phylogenetic inference. In this study, Aethalion reticulatum (Aethalionidae)
      spermatozoa were examined by light and electron microscopy. The head of the
      spermatozoa is composed of an acrosome and a nucleus. The nucleus is linear and
      filled with compact chromatin but has electron-lucid spaces. The centriole
      adjunct initiates parallel to the nucleus and terminates in the region anterior
      to the mitochondrial derivatives. Flagella consist of an axoneme, two
      mitochondrial derivatives and two accessory bodies and the axoneme has the
      typical 9+9+2 microtubule pattern. The mitochondrial derivatives are symmetric.
      The accessory bodies are long and are shaped like a half moon when viewed from a
      cross-section. The presence of accessory bodies differs from other species of
      Cicadomorpha previously studied. Spermatozoa morphology of other Auchenorrhyncha
      families can reveal synapomorphies and contribute to systematics of the suborder.

PMID- 20047836
TI  - Microstructure change in poly(ethersulfone) films by swift heavy ions.
AB  - PES membrane of thickness 25 microm was irradiated by Cl(9+) ions of energy 100
      MeV at IUAC, New Delhi. Microstructure changes due to exposure to high-energy
      ions were investigated by Fourier transform infrared (FTIR) and
      ultraviolet/visible (UV/vis) absorption spectroscopies, X-ray diffraction
      technique and by dynamic mechanical analysis (DMA). A significant loss of
      crystallinity is observed by the XRD data. Particle size or grain size calculated
      using Scherrer formula indicates measurable change in particle size of irradiated
      samples. The polymer chain scissions and structure degradations are expected to
      occur for irradiated samples. Optical properties of the films were changed due to
      irradiation that could be clearly seen in the absorption spectra. FTIR does not
      show the remarkable change in the irradiated samples, but there is some change in
      the surface roughness observed by AFM.

PMID- 20047837
TI  - On replacing Am-Be neutron sources in compensated porosity logging tools.
AB  - Authors explored the direct replacement of Am-Be neutron sources in neutron
      porosity logging tools through Monte Carlo simulations using MCNP5. (252)Cf and
      electronic accelerator neutron sources based on the Deuterium-Tritium fusion
      reaction were considered. Between the sources, a tradeoff was noted between
      sensitivity to the presence of hydrogen and uncertainty due to counting
      statistics. It was concluded that both replacement sources as well as accelerator
      sources based on the Deuterium-Deuterium fusion reaction warrant further
      consideration as porosity log sources.

PMID- 20047838
TI  - Optimizing the TLD-100 readout system for various radiotherapy beam doses using
      the Taguchi methodology.
AB  - The TLD-100 readout system was optimized for various radiotherapy beam doses
      using the Taguchi method. The radiotherapy beam was produced by a Varian 21EX
      linear accelerator (LINAC) at 6MV. The beam doses were 50, 100 and 150cGy, and
      the measured data in each group were averaged from three TLD-100 chips. A total
      of nine combinations of four parameters were arranged, in the manner suggested by
      Taguchi. The four parameters were defined as initial temperature, heating rate,
      preheat time and maximum set temperature of the readout system during TLD
      reading. The loss function eta adopted herein was specifically defined to satisfy
      the requirements of both sharp linearity and good reproducibility of the TLD
      reading at various radiotherapy beam doses. The optimized values were: (1) 50(
      composite function)C for initial temperature, (2) 3 (degrees C)/s for heating
      rate, (3) 5 min for the TLD preheat time and (4) 250 degrees C for the maximum
      temperature for TLD reading. Additionally, the parameters that dominated the TLD
      readout were: (1) initial temperature, (2) heating rate and (4) maximum
      temperature setting for TLD reading; and the minor parameter was (3) TLD preheat
      time before reading. The interactions among the dominant parameters were also
      studied: no significant cross interaction occurred between initial temperature
      and heating rate or between initial temperature and maximum temperature. However,
      a complex cross-interaction existed between optimal heating rate and maximum
      temperature.

PMID- 20047839
TI  - PIXE analysis of trace elements in relation to chlorophyll concentration in
      Plantago ovata Forsk.
AB  - Plantago ovata Forsk - an economically important medicinal plant - was analyzed
      for trace elements and chlorophyll in a study of the effects of gamma radiation
      on physiological responses of the seedlings. Proton-induced X-ray emission (PIXE)
      technique was used to quantify trace elements in unirradiated and gamma
      irradiated plants at the seedling stage. The experiments revealed radiation
      induced changes in the trace element and chlorophyll concentrations.

PMID- 20047840
TI  - An unusual cause of pulmonary embolism.

PMID- 20047841
TI  - (EZ)-Cyclobilirubin formation from bilirubin in complex with serum albumin
      derived from various species.
AB  - We determined the specificity of photochemical changes of bilirubin in complex
      with serum albumin from various species. There were no general trends in the
      configurational photoisomerizations of (ZE)-bilirubin/(ZZ)-bilirubin and (EZ)
      bilirubin/(ZZ)-bilirubin associated with the albumins from various species as
      compared to those associated with human serum albumin. The absorbance spectra of
      bilirubin in complex with albumins from various species differed, indicating that
      the three-dimensional structures of (ZZ)-bilirubin bound to the various serum
      albumins, which are substrates of (ZE)- and (EZ)-bilirubin, differ among species.
      The rates of conversion of the (EZ)-bilirubin isomer into the structural
      cyclobilirubin isomer were similar for the albumins of chicken, rat, rabbit, dog,
      bovine, and pig, and were significantly slower than the rate for human serum
      albumin. This suggests that the three-domain human albumin has evolved to allow
      ready conversion of (EZ)-bilirubin to (EZ)-cyclobilirubin. Cyclobilirubin
      formation in a bilirubin-alpha-fetoprotein solution was much lower than that in a
      bilirubin-human serum albumin solution. It is believed that the ability of human
      serum albumin to facilitate the photochemical change of bilirubin was
      evolutionarily selected in response to neonatal jaundice in humans.

PMID- 20047842
TI  - Lung protective ventilation strategies in paediatrics-A review.
AB  - Ventilator Associated Lung Injury (VALI) is an iatrogenic phenomena that
      significantly impacts on the morbidity and mortality of critically ill patients.
      The hazards associated with mechanical ventilation are becoming increasingly
      understood courtesy of a large body of research. Barotrauma, volutrauma and
      biotrauma all play a role in VALI. Concomitant to this growth in understanding is
      the development of strategies to reduce the deleterious impact of mechanical
      ventilation. The majority of the research is based upon adult populations but
      with careful extrapolation this review will focus on paediatrics. This review
      article describes the physiological basis of VALI and discusses the various lung
      protective strategies that clinicians can employ to minimise its incidence and
      optimise outcomes for paediatric patients.

PMID- 20047844
TI  - How vestibular stimulation interacts with illusory hand ownership.
AB  - Artificial stimulation of the peripheral vestibular system has been shown to
      improve ownership of body parts in neurological patients, suggesting vestibular
      contributions to bodily self-consciousness. Here, we investigated whether
      galvanic vestibular stimulation (GVS) interferes with the mechanisms underlying
      ownership, touch, and the localization of one's own hand in healthy participants
      by using the "rubber hand illusion" paradigm. Our results show that left anodal
      GVS increases illusory ownership of the fake hand and illusory location of touch.
      We propose that these changes are due to vestibular interference with spatial
      and/or temporal mechanisms of visual-tactile integration leading to an
      enhancement of visual capture. As only left anodal GVS lead to such changes, and
      based on neurological data on body part ownership, we suggest that this
      vestibular interference is mediated by the right temporo-parietal junction and
      the posterior insula.

PMID- 20047845
TI  - Influence of risk of neurological impairment and procedure invasiveness on health
      professionals' management of procedural pain in neonates.
AB  - OBJECTIVES: To describe how (i) risk of neurological impairment (NI) and (ii)
      procedure invasiveness influence health professionals' assessment and management
      of procedural pain in neonates in the Neonatal Intensive Care Unit (NICU).
      DESIGN: Prospective observational study. SETTING: Three tertiary level NICUs in
      Canada. PARTICIPANTS: 114 neonates, 25-40 weeks gestational age (GA) undergoing
      painful procedures. MAIN OUTCOME MEASURES: Physical and behavioural pain
      indicators and pharmacological and nonpharmacological pain interventions.
      RESULTS: 114 neonates at high (Cohort A, n=35), moderate (Cohort B, n=25) and low
      (Cohort C, n=54) risk of NI were observed during 254 painful procedures performed
      by 147 health professionals. Physical pain indicators were used more frequently
      by health professionals to assess pain with Cohorts A and B than C (p<.05).
      Behavioural pain indicators were used similarly across Cohorts.
      Nonpharmacological interventions were implemented most frequently for pain
      management. Physical interventions were used with 84% of procedures across
      Cohorts; particularly for the most invasive procedures. Infants with the highest
      NI risk (Cohort A) received the most behavioural interventions (p<.05)
      irrespective of procedural invasiveness. Pharmacological interventions were
      implemented with 23.2% of procedures; Cohort B received pharmacological
      interventions most frequently (Cohort B>A, B>C, p<.05) and for increasingly
      invasive procedures (p<.05). CONCLUSIONS: Health professionals use
      multidimensional indicators to assess neonatal pain. Nonpharmacological
      interventions dominate pain management. NI risk status and procedure invasiveness
      are important contextual factors in neonatal pain assessment and management.

PMID- 20047846
TI  - Effects of eccentric jaw exercise on temporal summation in jaw-closing muscles of
      healthy subjects.
AB  - Eccentric jaw exercises has been known to cause muscle soreness but no studies
      have so far examined to what extent temporal summation mechanisms within the
      exercised muscles are changed. The purpose of the present study was to
      investigate the effects of an eccentric biting exercise on the temporal
      summation, mechanical pressure sensitivity and jaw muscle activity. A total of 15
      healthy men participated in a two-session-experiment: In one session, they
      performed 30 min controlled eccentric jaw exercise and the other session served
      as a no-exercise control. Soreness sensations at rest and during maximal biting,
      pressure pain thresholds (PPTs) and electromyographic (EMG) activity during
      maximal jaw biting were recorded before (baseline), immediately after (Post
      task), and 1 day after the exercise (1-day-after). The temporal summation ratio
      using intra-muscular electrical stimulation of the masseter was investigated at
      baseline and at 1-day-after. The eccentric jaw exercise was associated with
      significant increases in soreness sensation and decreased PPTs at Post-task and
      at 1-day-after. The EMG activity and biting force did not change. The summation
      ratio was significantly decreased at 1-day-after in both sessions. The present
      findings demonstrate that eccentric jaw exercise does not induce detectable
      changes in temporal summation. However, the summation ratio may have clinical
      utility to differentiate the location of sensitization.

PMID- 20047847
TI  - Human immunodeficiency virus-hepatitis C virus co-infection in pregnant women and
      perinatal transmission to infants in Thailand.
AB  - OBJECTIVES: The objectives of this study were to assess the prevalence and
      factors associated with hepatitis C virus (HCV) infection in human
      immunodeficiency virus (HIV)-infected and -uninfected Thai pregnant women and the
      rate of HCV transmission to their infants. PATIENTS AND METHODS: Study subjects
      included 1435 HIV-infected pregnant women and their infants, enrolled in a
      perinatal HIV prevention trial, and a control group of 448 HIV-uninfected
      pregnant women. Women were screened for HCV antibodies with an enzyme
      immunoassay. Positive results were confirmed by recombinant immunoblot and HCV
      RNA quantification. Infants were tested for HCV antibodies at 18 months or for
      HCV RNA at between 6 weeks and 6 months. RESULTS: Of the HIV-infected women, 2.9%
      were HCV-infected compared to 0.5% of HIV-uninfected women (p=0.001). Only
      history of intravenous drug use was associated with HCV infection in HIV-infected
      women. Ten percent of infants born to co-infected mothers acquired HCV. The risk
      of transmission was associated with a high maternal HCV RNA (p=0.012), but not
      with HIV-1 load or CD4 count. CONCLUSIONS: Acquisition of HCV through intravenous
      drug use partially explains the higher rate of HCV infection in HIV-infected Thai
      women than in HIV-uninfected controls. Perinatal transmission occurred in 10% of
      infants of HIV-HCV-co-infected mothers and was associated with high maternal HCV
      RNA.

PMID- 20047848
TI  - Evolution of methicillin-resistant Staphylococcus aureus clones in Latin America.
AB  - OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent
      nosocomial bacterial pathogen, associated with significant morbidity and
      mortality. The global incidence is increasing, and Latin America is no exception.
      This article reviews MRSA clonal distribution in Latin America and implications
      for clinical practice. DESIGN: A PubMed literature search (1966-2008) identified
      32 articles that characterized MRSA clones in Latin America. RESULTS: Data from
      these articles show that since 1990, several epidemic MRSA clones have spread in
      Latin America. The multidrug-resistant Brazilian clone is widespread, especially
      in Brazil and Argentina, but more recently clones with susceptibility to a range
      of antibiotics have been detected in Brazil, whereas in Argentina, as in Chile,
      Colombia and Paraguay, the multidrug-resistant Cordobes/Chilean clone prevails.
      In Mexico, the New York/Japan clone is most frequent. Data were not available
      from every country and, despite the increasing prevalence of community MRSA
      infections, most were collected from tertiary care centers. CONCLUSIONS: A
      variety of epidemic MRSA clones are circulating in Latin America, some of which
      harbor genes that encode multidrug resistance or enhanced pathogenicity.
      Continued collection and reporting of epidemiological data is crucial for
      effective prevention and treatment.

PMID- 20047849
TI  - The evolutionary context for herbivore-induced plant volatiles: beyond the 'cry
      for help'.
AB  - Attacks by herbivores elicit changes in the bouquet of volatiles released by
      plants. These herbivore-induced plant volatiles (HIPVs) have been interpreted as
      being indirect defenses. However, given that no studies have yet investigated
      whether HIPVs benefit the fitness of a plant, their defensive function remains to
      be established. Moreover, herbivores, pathogens, pollinators and competitors also
      respond to HIPVs and, in addition, neighbouring plants in native populations also
      emit volatiles that provide a background odour. These considerations enrich the
      evolutionary context of HIPVs and complicate predictions about their adaptive
      value. Molecular advances in our understanding of HIPV signaling and biosynthesis
      is enabling the creation of HIPV-'mute' and possibly HIPV-'deaf' plants. As we
      discuss here, such plants could be used for unbiased examination of the fitness
      value of HIPV emissions under natural conditions.

PMID- 20047850
TI  - Convergence and specificity in the Arabidopsis MAPK nexus.
AB  - Although mitogen-activated protein kinase (MAPK) signal transduction cascades are
      known regulators of various aspects of plant biology, our knowledge of these
      systems has been largely restricted to a small subset of the MAPKs. However,
      global analyses are now revealing that many more of these kinases are probably
      engaged in modulating developmental and fitness adaptation processes in the plant
      kingdom. In this review, we show how these new findings are beginning to define
      the overall architecture of plant MAPK signaling, with a particular focus on the
      interplay between the terminal MPKs and their activators, inactivators and
      cellular targets.

PMID- 20047851
TI  - Controlling ribozyme activity by metal ions.
AB  - The observed rates of ribozyme cleavage reactions are strongly dependent on the
      nature of the metal ion present. Metal ions can thereby exhibit a stronger
      inhibiting or accelerating effect compared to Mg(2+), which is usually considered
      the natural cofactor. Alkaline, alkaline earth, transition, d(10), and other
      metal ions are applied either to gain a spectroscopic handle on the metal center,
      and/or to elucidate the catalytic mechanism. Here we shortly review some of the
      most recent publications on the influence of different metal ions on catalysis of
      the hammerhead, hepatitis delta virus, and group II intron ribozymes. Comparison
      of the observed cleavage rates of hammerhead ribozymes with the metal ion
      affinities of different ligands reveals that these rates correlate perfectly with
      the intrinsic phosphate affinities of the metal ions involved.

PMID- 20047852
TI  - From molecule to model, from environment to evolution: an integrated view of
      growth and development.

PMID- 20047853
TI  - UV absorption and keto-enol tautomerism equilibrium of methoxy and dimethoxy 1,3
      diphenylpropane-1,3-diones.
AB  - UV absorption spectra of 1,3-diphenylpropane-1,3-dione (1), its three methoxy
      derivatives (2-4) and its six dimethoxy derivatives (5-10) in various solvents
      dissolved were collected. The keto-enol tautomerism equilibrium constant was
      calculated with (1)H NMR. The position of the methoxy group in 1,3
      diphenylpropane-1,3-dione was shown to have an influence on the molecule's UV
      absorption spectrum and the keto-enol tautomerism equilibrium constant. The
      methoxy group in the para position increases the absorption of radiation in the
      UV-A range. A shift to the keto form in the keto-enol tautomerism equilibrium is
      experienced by compounds with methoxy groups in ortho position. When two methoxy
      groups are present, the influence of their position is cumulative.

PMID- 20047854
TI  - Synthesis, spectroscopic studies and structures of square-planar nickel(II) and
      copper(II) complexes derived from 2-{(Z)-[furan-2-ylmethyl]imino]methyl}-6
      methoxyphenol.
AB  - Two new nickel(II) [Ni(L)(2)] and copper(II) [Cu(L)(2)] complexes have been
      synthesized with bidentate NO donor Schiff base ligand (2-{(Z)-[furan-2
      ylmethyl]imino]methyl}-6-methoxyphenol) (HL) and both complexes Ni(L)(2) and
      Cu(L)(2) have been characterized by elemental analyses, IR, UV-vis, (1)H, (13)C
      NMR, mass spectroscopy and room temperature magnetic susceptibility measurement.
      The tautomeric equilibria (phenol-imine, O-H...N and keto-amine, O...H-N forms)
      have been systemetically studied by using UV-vis absorption spectra for the
      ligand HL. The UV-vis spectra of this ligand HL were recorded and commented in
      polar, non-polar, acidic and basic media. The crystal structures of these
      complexes have also been determined by using X-ray crystallographic techniques.
      The complexes Ni(L)(2) and Cu(L)(2) crystallize in the monoclinic space group
      P2(1)/n and P2(1)/c with unit cell parameters: a=10.4552(3)A and 12.1667(4)A,
      b=8.0121(3)A and 10.4792(3)A, c=13.9625(4)A and 129.6616(3)A, V=1155.22(6)A(3)
      and 1155.22(6)A(3), D(x)=1.493 and 1.476 g cm(-3) and Z=2 and 2, respectively.
      The crystal structures were solved by direct methods and refined by full-matrix
      least squares to a find R=0.0377 and 0.0336 of for 2340 and 2402 observed
      reflections, respectively.

PMID- 20047855
TI  - Vibrational spectra and normal coordinate analysis of plant growth regulator 1
      naphthalene acetamide.
AB  - FT Raman and IR spectra of the biologically active molecule, 1-naphthalene
      acetamide (NA) have been recorded and analyzed. The equilibrium geometry, bonding
      features and harmonic vibrational wavenumbers of NA have been calculated with the
      help of B3LYP density functional theory (DFT) method. The assignments of the
      vibrational spectra have been carried out with the help of normal coordinate
      analysis (NCA) following the scaled quantum mechanical force field methodology
      (SQMFF). The downshifting of NH(2) stretching wavenumber indicates the formation
      of intermolecular N-Hcdots, three dots, centeredO hydrogen bonding. The NBO
      analysis confirms the occurrence of strong intermolecular hydrogen bonding in the
      molecule.

PMID- 20047843
TI  - Tumor and host factors that may limit efficacy of chemotherapy in non-small cell
      and small cell lung cancer.
AB  - While chemotherapy provides useful palliation, advanced lung cancer remains
      incurable since those tumors that are initially sensitive to therapy rapidly
      develop acquired resistance. Resistance may arise from impaired drug delivery,
      extracellular factors, decreased drug uptake into tumor cells, increased drug
      efflux, drug inactivation by detoxifying factors, decreased drug activation or
      binding to target, altered target, increased damage repair, tolerance of damage,
      decreased proapoptotic factors, increased antiapoptotic factors, or altered cell
      cycling or transcription factors. Factors for which there is now substantial
      clinical evidence of a link to small cell lung cancer (SCLC) resistance to
      chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P
      gp (for non-platinum agents). SPECT MIBI and Tc-TF scanning appears to predict
      chemotherapy benefit in SCLC. In non-small cell lung cancer (NSCLC), the
      strongest clinical evidence is for taxane resistance with elevated expression or
      mutation of class III beta-tubulin (and possibly alpha tubulin), platinum
      resistance and expression of ERCC1 or BCRP, gemcitabine resistance and RRM1
      expression, and resistance to several agents and COX-2 expression (although COX-2
      inhibitors have had minimal impact on drug efficacy clinically). Tumors
      expressing high BRCA1 may have increased resistance to platinums but increased
      sensitivity to taxanes. Limited early clinical data suggest that chemotherapy
      resistance in NSCLC may also be increased with decreased expression of cyclin B1
      or of Eg5, or with increased expression of ICAM, matrilysin, osteopontin, DDH,
      survivin, PCDGF, caveolin-1, p21WAF1/CIP1, or 14-3-3sigma, and that IGF-1R
      inhibitors may increase efficacy of chemotherapy, particularly in squamous cell
      carcinomas. Equivocal data (with some positive studies but other negative
      studies) suggest that NSCLC tumors with some EGFR mutations may have increased
      sensitivity to chemotherapy, while K-ras mutations and expression of GST-pi, RB
      or p27kip1 may possibly confer resistance. While limited clinical data suggest
      that p53 mutations are associated with resistance to platinum-based therapies in
      NSCLC, data on p53 IHC positivity are equivocal. To date, resistance-modulating
      strategies have generally not proven clinically useful in lung cancer, although
      small randomized trials suggest a modest benefit of verapamil and related agents
      in NSCLC.

PMID- 20047856
TI  - Comment on "Growth and characterization of glycine picrate single crystal" by T.
      Uma Devi et al. [Spectrochim. Acta A71 (2008) 340-343].
AB  - The crystal grown and characterized in the title paper in reality is diglycine
      picrate.

PMID- 20047857
TI  - The investigation of the interactions between CdSe quantum dots and human serum
      albumin by resonance Rayleigh scattering and second-order scattering spectra.
AB  - Human serum albumin (HSA) was the most abundant protein in human plasma and has
      significant physiological function. In Tris-HCl buffer solution (pH 7.4), water
      soluble semiconductor CdSe quantum dots (QDs) reacted with HSA and the products
      resulted in a great enhancement of the intensity of resonance Rayleigh scattering
      (RRS) and second-order scattering (SOS). Based on this, a new method was
      developed to investigate the interactions between QDs and HSA. The parameters
      with regard to determination were optimized, and the reaction mechanism was
      discussed. Under optimal conditions, the increments of scattering intensity
      (DeltaI) were directly proportional to the concentrations of HSA in the range of
      0.4-48.0 micromol L(-1). The detection limits were 0.10 micromol L(-1) for RRS
      method and 0.25 micromol L(-1) for SOS method. The proposed method was sensitive,
      simple and rapid. It has been successfully applied to the determination of HSA in
      human urine samples. Analytical results obtained with this novel assay were
      satisfactory.

PMID- 20047858
TI  - Solvatochromic, acid-base features and time effect of some azo dyes derived from
      1,3-benzothiazol-2-ylacetonitrile: experimental and semiempirical investigations.
AB  - The solvatochromism and other spectroscopic properties of seven azo dyes were
      studied, with a particular respect to the role of the solvent basicity, and
      interpreted with the aid of experimental findings and semiempirical data. The
      electronic absorption spectra of the dyes examined in different solvents combined
      with theoretical calculations showed that most of the investigated compounds
      coexist in the hydrazone and/or azo-enamine-common anion equilibrium or in the
      solely anionic form depending upon the nature of the solvent employed. These
      interesting features open up possibilities for the use of these compounds in
      analytical chemistry as acid-base indicators. Furthermore, both of intermolecular
      and intramolecular charge transfer equilibria have been reflected by experimental
      absorption spectra of compounds 4 and 5. The enthalpies of formation predicted at
      PM6 (COSMO) and PM6/CI (COSMO) for the ground (S(0)) and excited (S(1)) states,
      respectively have been successfully used for the explanation of the observed
      bathchromic shift in non-polar solvents. The effect of time on the longer
      wavelength visible band of compound 7 has been thoroughly investigated.

PMID- 20047859
TI  - The preoperative assessment of obstetric patients.
AB  - The importance of early identification and management of the high-risk obstetric
      patient is emphasised in the Confidential Enquiry into Maternal and Child Health
      (CEMACH) report. High-risk patients who need anaesthetic input include those with
      airway problems, cardiorespiratory disease and rare genetic conditions, such as
      malignant hyperthermia and suxamethonium apnoea. Anaesthetic options for labour
      analgesia as well as anaesthesia for operative delivery will need to be discussed
      in detail with the patient if a delivery management plan is to be constructed.
      Input from other medical teams, such as cardiologists or haematologists, are
      often needed. Ultimately, these measures should reduce maternal morbidity and
      mortality.

PMID- 20047860
TI  - Oligometastases and oligo-recurrence: the new era of cancer therapy.
AB  - Recurrence or metastasis of cancer has been considered to occur in the last stage
      of the patient's life. However, the new notions of oligometastases and oligo
      recurrence have been proposed and the paradigm shift in the conceptualization of
      cancer metastasis or cancer recurrence. Oligometastases is the state in which the
      patient shows distant relapse in only a limited number of regions. Local therapy
      such as surgery, radiotherapy and radiofrequency ablation for the relapsed sites
      could thus improve patient's survival. On the other hand, oligo-recurrence is a
      notion similar to oligometastases. However, the conditions of oligo-recurrence
      has a primary site of the cancer controlled, meaning that all gross recurrent or
      metastatic sites could be treated using local therapy.

PMID- 20047861
TI  - Current status and problems in development of molecular target agents for
      gastrointestinal malignancy in Japan.
AB  - Since late 1990s, many molecular target agents have been introduced to clinical
      trials for various kinds of tumors, and some of them showing significant benefits
      have been approved. However, these global trials were mainly conducted outside
      Japan, and the 'drag lag' has been a serious problem in Japan recently. Nowadays,
      Japanese institutions have been participating in some global trials, and the drug
      lags are getting shorter. For colorectal cancer, molecular target agents such as
      bevacizumab and cetuximab have been approved in Japan, resulting in improved
      clinical outcomes. For gastric cancer, Japanese institutions not only contribute
      to the global Phase III trials of trastuzumab and bevacizumab but also show
      leadership in the early development of other new agents. For pancreatic cancer,
      only erlotinib has shown a survival benefit in these 10 years. Worldwide approach
      including Japan is warranted to achieve better clinical outcomes. For liver
      cancer, although Japanese institutions did not participate even in the Asian
      trial of sorafenib, it has been approved in Japan. For esophageal cancer, because
      there has been no new molecular target agents developed by pharmaceutical
      companies, investigator-initiated registration trial will play an important role.
      For all gastrointestinal malignancies, molecular target agents have made a
      progress in their treatments. In the near future, Japanese institutions will
      participate in more and more global trials and should play a specific role in
      worldwide drug development. Furthermore, the optimal use of these new drugs,
      molecular target agents, based on the daily practice should also be explored in
      Japan.

PMID- 20047862
TI  - Cisplatin and etoposide as first-line chemotherapy for poorly differentiated
      neuroendocrine carcinoma of the hepatobiliary tract and pancreas.
AB  - OBJECTIVE: The combination chemotherapy consisting of cisplatin and etoposide,
      one of the standard regimens for small cell lung cancer, has been widely used to
      treat extrapulmonary poorly differentiated neuroendocrine carcinomas. However,
      there were no prior reports limited to the hepatobiliary tract and pancreas as
      the primary sites. METHODS: We reviewed the cases in our database from October
      1995 to January 2009 and retrospectively examined the clinical data of patients,
      with unresectable or recurrent poorly differentiated neuroendocrine carcinoma
      arising from the hepatobiliary tract and pancreas, who received combination
      chemotherapy with cisplatin and etoposide as the first-line treatment. The
      chemotherapy regimen consisted of cisplatin 80 mg/m(2) given intravenously on day
      1 and etoposide 100 mg/m(2) intravenously on days 1-3, repeated every 3-4 weeks.
      RESULTS: Twenty-one patients were treated with the above regimen of cisplatin and
      etoposide combination chemotherapy. The primary tumor site was the liver in 2
      patients, gallbladder in 8 patients, pancreas in 10 patients and ampulla of Vater
      in 1 patient. Although no complete responses were obtained, three patients had
      partial responses, resulting in an overall response rate of 14%. Median
      progression-free survival was 1.8 months, and median overall survival was 5.8
      months. The major adverse events were myelosuppression and gastrointestinal
      toxicities, with Grade 3 or 4 neutropenia (90%), nausea (33%) and anorexia (24%).
      CONCLUSIONS: Cisplatin and etoposide combination as the first-line chemotherapy
      for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma
      had only marginal antitumor activity and relatively severe toxicity compared with
      previous studies on extrapulmonary poorly differentiated neuroendocrine carcinoma
      treated with the same regimen.

PMID- 20047863
TI  - Darwin and the evolution of flowers.

PMID- 20047864
TI  - Darwin's legacy: the forms, function and sexual diversity of flowers.
AB  - Charles Darwin studied floral biology for over 40 years and wrote three major
      books on plant reproduction. These works have provided the conceptual foundation
      for understanding floral adaptations that promote cross-fertilization and the
      mechanisms responsible for evolutionary transitions in reproductive systems. Many
      of Darwin's insights, gained from careful observations and experiments on diverse
      angiosperm species, remain remarkably durable today and have stimulated much
      current research on floral function and the evolution of mating systems. Here I
      review Darwin's seminal contributions to reproductive biology and provide an
      overview of the current status of research on several of the main topics to which
      he devoted considerable effort, including the consequences to fitness of cross-
      versus self-fertilization, the evolution and function of stylar polymorphisms,
      the adaptive significance of heteranthery, the origins of dioecy and related
      gender polymorphisms, and the transition from animal pollination to wind
      pollination. Post-Darwinian perspectives on floral function now recognize the
      importance of pollen dispersal and male outcrossed siring success in shaping
      floral adaptation. This has helped to link work on pollination biology and mating
      systems, two subfields of reproductive biology that remained largely isolated
      during much of the twentieth century despite Darwin's efforts towards
      integration.

PMID- 20047865
TI  - Diversity in obscurity: fossil flowers and the early history of angiosperms.
AB  - In the second half of the nineteenth century, pioneering discoveries of rich
      assemblages of fossil plants from the Cretaceous resulted in considerable
      interest in the first appearance of angiosperms in the geological record.
      Darwin's famous comment, which labelled the 'rapid development' of angiosperms an
      'abominable mystery', dates from this time. Darwin and his contemporaries were
      puzzled by the relatively late, seemingly sudden and geographically widespread
      appearance of modern-looking angiosperms in Late Cretaceous floras. Today, the
      early diversification of angiosperms seems much less 'rapid'. Angiosperms were
      clearly present in the Early Cretaceous, 20-30 Myr before they attained the level
      of ecological dominance reflected in some mid-Cretaceous floras, and angiosperm
      leaves and pollen show a distinct pattern of steadily increasing diversity and
      complexity through this interval. Early angiosperm fossil flowers show a similar
      orderly diversification and also provide detailed insights into the changing
      reproductive biology and phylogenetic diversity of angiosperms from the Early
      Cretaceous. In addition, newly discovered fossil flowers indicate considerable,
      previously unrecognized, cryptic diversity among the earliest angiosperms known
      from the fossil record. Lineages that today have an herbaceous or shrubby habit
      were well represented. Monocotyledons, which have previously been difficult to
      recognize among assemblages of early fossil angiosperms, were also diverse and
      prominent in many Early Cretaceous ecosystems.

PMID- 20047866
TI  - A duplicate gene rooting of seed plants and the phylogenetic position of
      flowering plants.
AB  - Flowering plants represent the most significant branch in the tree of land
      plants, with respect to the number of extant species, their impact on the shaping
      of modern ecosystems and their economic importance. However, unlike so many
      persistent phylogenetic problems that have yielded to insights from DNA sequence
      data, the mystery surrounding the origin of angiosperms has deepened with the
      advent and advance of molecular systematics. Strong statistical support for
      competing hypotheses and recent novel trees from molecular data suggest that the
      accuracy of current molecular trees requires further testing. Analyses of
      phytochrome amino acids using a duplicate gene-rooting approach yield trees that
      unite cycads and angiosperms in a clade that is sister to a clade in which Gingko
      and Cupressophyta are successive sister taxa to gnetophytes plus Pinaceae.
      Application of a cycads + angiosperms backbone constraint in analyses of a
      morphological dataset yields better resolved trees than do analyses in which
      extant gymnosperms are forced to be monophyletic. The results have implications
      both for our assessment of uncertainty in trees from sequence data and for our
      use of molecular constraints as a way to integrate insights from morphological
      and molecular evidence.

PMID- 20047867
TI  - Defining the limits of flowers: the challenge of distinguishing between the
      evolutionary products of simple versus compound strobili.
AB  - Recent phylogenetic reconstructions suggest that axially condensed flower-like
      structures evolved iteratively in seed plants from either simple or compound
      strobili. The simple-strobilus model of flower evolution, widely applied to the
      angiosperm flower, interprets the inflorescence as a compound strobilus. The
      conifer cone and the gnetalean 'flower' are commonly interpreted as having
      evolved from a compound strobilus by extreme condensation and (at least in the
      case of male conifer cones) elimination of some structures present in the
      presumed ancestral compound strobilus. These two hypotheses have profoundly
      different implications for reconstructing the evolution of developmental genetic
      mechanisms in seed plants. If different flower-like structures evolved
      independently, there should intuitively be little commonality of patterning
      genes. However, reproductive units of some early-divergent angiosperms, including
      the extant genus Trithuria (Hydatellaceae) and the extinct genus Archaefructus
      (Archaefructaceae), apparently combine features considered typical of flowers and
      inflorescences. We re-evaluate several disparate strands of comparative data to
      explore whether flower-like structures could have arisen by co-option of flower
      expressed patterning genes into independently evolved condensed inflorescences,
      or vice versa. We discuss the evolution of the inflorescence in both gymnosperms
      and angiosperms, emphasising the roles of heterotopy in dictating gender
      expression and heterochrony in permitting internodal compression.

PMID- 20047868
TI  - The evolution of floral biology in basal angiosperms.
AB  - In basal angiosperms (including ANITA grade, magnoliids, Choranthaceae,
      Ceratophyllaceae) almost all bisexual flowers are dichogamous (with male and
      female functions more or less separated in time), and nearly 100 per cent of
      those are protogynous (with female function before male function). Movements of
      floral parts and differential early abscission of stamens in the male phase are
      variously associated with protogyny. Evolution of synchronous dichogamy based on
      the day/night rhythm and anthesis lasting 2 days is common. In a few clades in
      Magnoliales and Laurales heterodichogamy has also evolved. Beetles, flies and
      thrips are the major pollinators, with various degrees of specialization up to
      large beetles and special flies in some large-flowered Nymphaeaceae,
      Magnoliaceae, Annonaceae and Aristolochiaceae. Unusual structural specializations
      are involved in floral biological adaptations (calyptras, inner staminodes,
      synandria and food bodies, and secretory structures on tepals, stamens and
      staminodes). Numerous specializations that are common in monocots and eudicots
      are absent in basal angiosperms. Several families are poorly known in their
      floral biology.

PMID- 20047869
TI  - The evolution and loss of oil-offering flowers: new insights from dated
      phylogenies for angiosperms and bees.
AB  - The interactions between bees that depend on floral oil for their larvae and
      flowers that offer oil involve an intricate mix of obligate and facultative
      mutualisms. Using recent phylogenies, new data on oil-offering Cucurbitaceae, and
      molecular-dating, we ask when and how often oil-offering flowers and oil-foraging
      bees evolved, and how frequently these traits were lost in the cause of
      evolution. Local phylogenies and an angiosperm-wide tree show that oil flowers
      evolved at least 28 times and that floral oil was lost at least 36-40 times. The
      oldest oil flower systems evolved shortly after the K/T boundary independently in
      American Malpighiaceae, tropical African Cucurbitaceae and Laurasian Lysimachia
      (Myrsinaceae); the ages of the South African oil flower/oil bee systems are less
      clear. Youngest oil flower clades include Calceolaria (Calceolariaceae),
      Iridaceae, Krameria (Krameriaceae) and numerous Orchidaceae, many just a few
      million years old. In bees, oil foraging evolved minimally seven times and dates
      back to at least 56 Ma (Ctenoplectra) and 53 Ma (Macropis). The co-occurrence of
      older and younger oil-offering clades in three of the four geographical regions
      (but not the Holarctic) implies that oil-foraging bees acquired additional oil
      hosts over evolutionary time. Such niche-broadening probably started with
      exploratory visits to flowers resembling oil hosts in scent or colour, as
      suggested by several cases of Muellerian or Batesian mimicry involving oil
      flowers.

PMID- 20047870
TI  - Diversity and evolution of floral structure among early diverging lineages in the
      Ericales.
AB  - This is a combination of review and original data on floral structure and
      diversity in the two earliest diverging lineages of the Ericales, i.e. the
      balsaminoids, comprising Balsaminaceae, Marcgraviaceae and Tetrameristaceae, and
      the polemonioids, comprising Fouquieriaceae and Polemoniaceae. Each clade is
      strongly supported in molecular studies, while structural synapomorphies have
      largely been lacking. For the balsaminoid families, we compare floral morphology,
      anatomy and histology among selected taxa and find that the entire clade is
      strongly supported by the shared presence of nectariferous tissue in the floral
      periphery, thread-like structures on anthers, truncate stigmas, secretion in the
      ovary, as well as mucilage cells, raphides and tannins in floral tissues. A
      possible sister group relationship between Balsaminaceae and Tetrameristaceae is
      supported by the shared presence of post-genital fusion of filaments and ovary
      and a star-shaped stylar canal. For polemonioids, we document unexpected
      diversity of floral features in Polemoniaceae, partly providing structural links
      to Fouquieriaceae. Features include cochlear and quincuncial corolla aestivation,
      connective protrusions, ventrifixed anthers and nectariferous tissue in the base
      of the ovary. In addition, we outline future directions for research on floral
      structure in the Ericales and briefly discuss the general importance of
      structural studies for our understanding of plant phylogeny and evolution.

PMID- 20047871
TI  - On 'various contrivances': pollination, phylogeny and flower form in the
      Solanaceae.
AB  - Members of the euasterid angiosperm family Solanaceae have been characterized as
      remarkably diverse in terms of flower morphology and pollinator type. In order to
      test the relative contribution of phylogeny to the pattern of distribution of
      floral characters related to pollination, flower form and pollinators have been
      mapped onto a molecular phylogeny of the family. Bilateral flower symmetry
      (zygomorphy) is prevalent in the basal grades of the family, and more derived
      clades have flowers that are largely radially symmetric, with some parallel
      evolution of floral bilateralism. Pollinator types ('syndromes') are extremely
      homoplastic in the family, but members of subfamily Solanoideae are exceptional
      in being largely bee pollinated. Pollinator relationships in those genera where
      they have been investigated more fully are not as specific as flower morphology
      and the classical pollinator syndrome models might suggest, and more detailed
      studies in some particularly variable genera, such as Iochroma and Nicotiana, are
      key to understanding the role of pollinators in floral evolution and adaptive
      radiation in the family. More studies of pollinators in the field are a priority.

PMID- 20047872
TI  - Speciation genes in the genus Petunia.
AB  - A major innovation in angiosperms is the recruitment of animal pollinators as a
      means to enhance the efficiency and specificity of pollen transfer. The
      implementation of this reproductive strategy involved the rapid and presumably
      coordinated evolution of multiple floral traits. A major question concerns the
      molecular identity of the genetic polymorphisms that specify the phenotypic
      differences between distinct pollination syndromes. Here, we report on our work
      with Petunia, an attractive model system for quantitative plant genetics and
      genomics. From interspecific crosses, we obtained F2 plants that differed in the
      length of the floral tube or the size of the limb. We used these plants to study
      the behaviour of the hawkmoth pollinator, Manduca sexta. Plants with larger limbs
      were preferentially visited, consistent with the notion that flower size affects
      visibility under low light conditions. The moths also displayed an innate
      preference for shorter tubes. However, in those cases that flowers with long
      tubes were chosen, the animals fed for equal time. Thus, the perception of tube
      length may help the moths, early on, to avoid those plants that are more
      difficult to handle.

PMID- 20047873
TI  - The evolutionary-developmental analysis of plant microRNAs.
AB  - MicroRNAs (miRNAs) control many important aspects of plant development,
      suggesting these molecules may also have played key roles in the evolution of
      developmental processes in plants. However, evolutionary-developmental (evo-devo)
      studies of miRNAs have been held back by technical difficulties in gene
      identification. To help solve this problem, we have developed a two-step
      procedure for the efficient identification of miRNA genes in any plant species.
      As a test case, we have studied the evolution of the MIR164 family in the
      angiosperms. We have identified novel MIR164 genes in three species occupying key
      phylogenetic positions and used these, together with published sequence data, to
      partially reconstruct the evolution of the MIR164 family since the last common
      ancestor of the extant flowering plants. We use our evolutionary reconstruction
      to discuss potential roles for MIR164 genes in the evolution of leaf shape and
      carpel closure in the angiosperms. The techniques we describe may be applied to
      any miRNA family and should thus enable plant evo-devo to begin to investigate
      the contributions miRNAs have made to the evolution of plant development.

PMID- 20047875
TI  - Riding across the selection landscape: fitness consequences of annual variation
      in reproductive characteristics.
AB  - Evolutionary models estimating phenotypic selection in character size usually
      assume that the character is invariant across reproductive bouts. We show that
      variation in the size of reproductive traits may be large over multiple events
      and can influence fitness in organisms where these traits are produced anew each
      season. With data from populations of two orchid species, Caladenia valida and
      Tolumnia variegata, we used Bayesian statistics to investigate the effect on the
      distribution in fitness of individuals when the fitness landscape is not flat and
      when characters vary across reproductive bouts. Inconsistency in character size
      across reproductive periods within an individual increases the uncertainty of
      mean fitness and, consequently, the uncertainty in individual fitness. The
      trajectory of selection is likely to be muddled as a consequence of variation in
      morphology of individuals across reproductive bouts. The frequency and amplitude
      of such changes will certainly affect the dynamics between selection and genetic
      drift.

PMID- 20047874
TI  - Aquilegia as a model system for the evolution and ecology of petals.
AB  - The ranunculid genus Aquilegia holds extraordinary promise as a model system for
      investigating a wide range of questions relating to the evolution and ecology of
      petals. New genetic and genomic resources, including an extensive EST database,
      BAC libraries and physical maps, as well as virus-induced gene silencing are
      facilitating this research on multiple fronts. At the developmental genetic
      level, Aquilegia has been important for elucidating the developmental programme
      for specifying petals and petaloid characteristics. Data suggest that duplication
      events among the petal and stamen identity genes have resulted in sub- and
      neofunctionalization. This expansion of gene function does not include the
      petaloidy of Aquilegia sepals, however, which does not depend on the same loci
      that control identity of the second whorl petals. Of special interest is the
      elaboration of the petal into a nectar spur, a major innovation for the genus.
      Intra- and interspecific variation in the shape and colour of petals, especially
      the spurs, has been shown to be adaptative for different pollinators. Thus,
      understanding the genetic basis of these traits will help us connect the
      ecological interactions driving speciation with the genetic changes responsible
      for remodelling morphology. Progress in this area has focused on the multiple,
      parallel transitions in flower colour and nectar spur length across the genus.
      For flower colour, upstream transcription factors appear to be primarily targets
      of natural selection. Thus research in Aquilegia spans the initial evolution of
      petals and petaloidy to the diversification of petal morphology to the ecological
      basis of petal form, thereby providing a comprehensive picture of the
      evolutionary biology of this critical angiosperm feature.

PMID- 20047876
TI  - The pollination niche and its role in the diversification and maintenance of the
      southern African flora.
AB  - The flora of southern Africa has exceptional species richness and endemism,
      making it an ideal system for studying the patterns and processes of evolutionary
      diversification. Using a wealth of recent case studies, I examine the evidence
      for pollinator-driven diversification in this flora. Pollination systems, which
      represent available niches for ecological diversification, are characterized in
      southern Africa by a high level of ecological and evolutionary specialization on
      the part of plants, and, in some cases, by pollinators as well. These systems are
      asymmetric, with entire plant guilds commonly specialized for a particular
      pollinator species or functional type, resulting in obvious convergent floral
      evolution among guild members. Identified modes of plant lineage diversification
      involving adaptation to pollinators in these guilds include (i) shifts between
      pollination systems, (ii) divergent use of the same pollinator, (iii)
      coevolution, (iv) trait tracking, and (v) floral mimicry of different model
      species. Microevolutionary studies confirm that pollinator shifts can be
      precipitated when a plant species encounters a novel pollinator fauna on its
      range margin, and macroevolutionary studies confirm frequent pollinator shifts
      associated with lineage diversification. As Darwin first noted, evolutionary
      specialization for particular pollinators, when resulting in ecological
      dependency, may increase the risk of plant extinction. I thus also consider the
      evidence that disturbance provokes pollination failure in some southern African
      plants with specialized pollination systems.

PMID- 20047877
TI  - Pollination ecology and the possible impacts of environmental change in the
      Southwest Australian Biodiversity Hotspot.
AB  - The Southwest Australian Biodiversity Hotspot contains an exceptionally diverse
      flora on an ancient, low-relief but edaphically diverse landscape. Since European
      colonization, the primary threat to the flora has been habitat clearance, though
      climate change is an impending threat. Here, we review (i) the ecology of
      nectarivores and biotic pollination systems in the region, (ii) the evidence that
      trends in pollination strategies are a consequence of characteristics of the
      landscape, and (iii) based on these discussions, provide predictions to be tested
      on the impacts of environmental change on pollination systems. The flora of
      southwestern Australia has an exceptionally high level of vertebrate pollination,
      providing the advantage of highly mobile, generalist pollinators. Nectarivorous
      invertebrates are primarily generalist foragers, though an increasing number of
      colletid bees are being recognized as being specialized at the level of plant
      family or more rarely genus. While generalist pollination strategies dominate
      among insect-pollinated plants, there are some cases of extreme specialization,
      most notably the multiple evolutions of sexual deception in the Orchidaceae.
      Preliminary data suggest that bird pollination confers an advantage of greater
      pollen movement and may represent a mechanism for minimizing inbreeding in
      naturally fragmented populations. The effects of future environmental change are
      predicted to result from a combination of the resilience of pollination guilds
      and changes in their foraging and dispersal behaviour.

PMID- 20047878
TI  - Floral adaptation and diversification under pollen limitation.
AB  - Pollen limitation (PL) of seed production creates unique conditions for
      reproductive adaptation by angiosperms, in part because, unlike under ovule or
      resource limitation, floral interactions with pollen vectors can contribute to
      variation in female success. Although the ecological and conservation
      consequences of PL have received considerable attention in recent times, its
      evolutionary implications are poorly appreciated. To identify general influences
      of PL on reproductive adaptation compared with those under other seed-production
      limits and their implications for evolution in altered environments, we derive a
      model that incorporates pollination and post-pollination aspects of PL. Because
      PL always favours increased ovule fertilization, even when population dynamics
      are not seed limited, it should pervasively influence selection on reproductive
      traits. Significantly, under PL the intensity of inbreeding does not determine
      whether outcrossing or autonomous selfing can evolve, although it can affect
      which response is most likely. Because the causes of PL are multifaceted in both
      natural and anthropogenically altered environments, the possible outcrossing
      solutions are diverse and context dependent, which may contribute to the
      extensive variety of angiosperm reproductive characteristics. Finally, the
      increased adaptive options available under PL may be responsible for positive
      global associations between it and angiosperm diversity.

PMID- 20047879
TI  - jORCA: easily integrating bioinformatics Web Services.
AB  - MOTIVATION: Web services technology is becoming the option of choice to deploy
      bioinformatics tools that are universally available. One of the major strengths
      of this approach is that it supports machine-to-machine interoperability over a
      network. However, a weakness of this approach is that various Web Services differ
      in their definition and invocation protocols, as well as their communication and
      data formats-and this presents a barrier to service interoperability. RESULTS:
      jORCA is a desktop client aimed at facilitating seamless integration of Web
      Services. It does so by making a uniform representation of the different web
      resources, supporting scalable service discovery, and automatic composition of
      workflows. Usability is at the top of the jORCA agenda; thus it is a highly
      customizable and extensible application that accommodates a broad range of user
      skills featuring double-click invocation of services in conjunction with advanced
      execution-control, on the fly data standardization, extensibility of viewer plug
      ins, drag-and-drop editing capabilities, plus a file-based browsing style and
      organization of favourite tools. The integration of bioinformatics Web Services
      is made easier to support a wider range of users. .

PMID- 20047880
TI  - Defects in dynamics and functions of actin filament in Arabidopsis caused by the
      dominant-negative actin fiz1-induced fragmentation of actin filament.
AB  - We isolated frizzy1 (fiz1), a novel dominant actin mutant from Arabidopsis. In
      the fiz1 mutant, Glu272 was substituted with lysine in the hydrophobic loop of
      ACT8, which is very important for the polymerization. Live imaging of actin
      filaments revealed that the fiz1 mutation induced fragmentation of actin
      filaments in a semi-dominant manner. In addition, the dynamics of Golgi stacks
      and mitochondria were disrupted by the fiz1 effects. From these results, it was
      strongly suggested that the fiz1 mutation had dominant-negative effects on actin
      polymerization, which causes defects in the functions of actin filaments such as
      organelle transport.

PMID- 20047881
TI  - Hemopexin: anti-inflammatory, pro-inflammatory, or both?

PMID- 20047883
TI  - Editorial: glycyrrhizin against multi-resistant bacteria?

PMID- 20047885
TI  - Editorial: memory CD8 T cells now join "Club 21".
AB  - In this volume, Nguyen and Weng [( 1) ] show an intriguing study in which they
      observed an antagonizing effect by IL-21 on the IL-7- or IL-15-driven expansion
      of CD28(-) nonfunctional memory CD8 T cells and thereby, proposed a new role for
      IL-21 to keep the memory pool fresh and competent. I will summarize previous
      studies and discuss the recent advancement in this context.

PMID- 20047884
TI  - Editorial: quality versus quantity in myeloid infection by a herpesvirus: more
      than one way to skin the CCAAT?

PMID- 20047886
TI  - Editorial: acute inflammation in obesity: IL-17A in the middle of the battle.

PMID- 20047887
TI  - Editorial: macrophage functional phenotypes: no alternatives in dermal wound
      healing?

PMID- 20047888
TI  - Editorial: leukocyte trafficking and matrix metalloproteinase-8 in obliterative
      bronchiolitis.

PMID- 20047889
TI  - A Valepotriate Fraction of Valeriana glechomifolia Shows Sedative and Anxiolytic
      Properties and Impairs Recognition But Not Aversive Memory in Mice.
AB  - Plants of the genus Valeriana (Valerianaceae) are used in traditional medicine as
      a mild sedative, antispasmodic and tranquilizer in many countries. This study was
      undertaken to explore the neurobehavioral effects of systemic administration of a
      valepotriate extract fraction of known quantitative composition of Valeriana
      glechomifolia (endemic of southern Brazil) in mice. Adult animals were treated
      with a single intraperitoneal injection of valepotriate fraction (VF) in the
      concentrations of 1, 3 or 10 mg kg(-1), or with vehicle in the pre-training
      period before each behavioral test. During the exploration of an open field, mice
      treated with 10 mg kg(-1) of VF showed reduced locomotion and exploratory
      behavior. Although overall habituation sessions for locomotion and exploratory
      behavior among vehicle control and doses of VF were not affected, comparison
      between open-field and habituation sessions within each treatment showed that VF
      administration at 1 and 10 mg kg(-1) impaired habituation. In the elevated plus
      maze test, mice treated with VF (10 mg kg(-1)) showed a significant increase in
      the percentage of time spent in the open arms without significant effects in the
      number of total arm entries. VF at 3 mg kg(-1) produced an impairment of novel
      object recognition memory. In contrast, VF did not affect fear-related memory
      assessed in an inhibitory avoidance task. The results indicate that VF can have
      sedative effects and affect behavioral parameters related to recognition memory. 

PMID- 20047890
TI  - Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of
      Cymbopogon ambiguus.
AB  - Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in
      Australia for the treatment of headache, chest infections and muscle cramps. The
      aim of the present study was to screen and identify bioactive compounds from C.
      ambiguus that could explain this plant's anti-headache activity. A
      dichloromethane extract of C. ambiguus was identified as having activity in
      adenosine-diphosphate-induced human platelet aggregation and serotonin-release
      inhibition bioassays. Subsequent fractionation of this extract led to the
      isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and
      trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent
      inhibition of ADP-induced human platelet serotonin release, only eugenol
      displayed potent inhibitory activity with an IC50 value of 46.6  MU M, in
      comparison to aspirin, with an IC50 value of 46.1  MU M. These findings provide
      evidence to support the therapeutic efficacy of C. ambiguus in the non
      conventional treatment of headache and inflammatory conditions. 

PMID- 20047891
TI  - Antioxidant Potential of Momordica Charantia in Ammonium Chloride-Induced
      Hyperammonemic Rats.
AB  - The present study was aimed to investigate the antioxidant potential of Momordica
      charantia fruit extract (MCE) in ammonium chloride-induced (AC) hyperammonemic
      rats. Experimental hyperammonemia was induced in adult male Wistar rats (180-200
      g) by intraperitoneal injections of ammonium chloride (100 mg kg(-1) body weight)
      thrice a week. The effect of oral administration (thrice a week for 8 consecutive
      weeks) of MCE (300 mg kg(-1) body weight) on blood ammonia, plasma urea, serum
      liver marker enzymes and oxidative stress biomarkers in normal and experimental
      animals was analyzed. Hyperammonemic rats showed a significant increase in the
      activities of thiobarbituric acid reactive substances, hydroperoxides and liver
      markers (alanine transaminase, aspartate transaminase and alkaline phosphatase),
      and the levels of glutathione peroxidase, superoxide dismutase, catalase and
      reduced glutathione were decreased in the liver and brain tissues. Treatment with
      MCE normalized the above-mentioned changes in hyperammonemic rats by reversing
      the oxidant-antioxidant imbalance during AC-induced hyperammonemia, and offered
      protection against hyperammonemia. Our results indicate that MCE exerting the
      antioxidant potentials and maintaining the cellular integrity of the liver tissue
      could offer protection against AC-induced hyperammonemia. However, the exact
      underlying mechanism is yet to be investigated, and examination of the efficacy
      of the active constituents of the M. charantia on hyperammonemia is desirable. 

PMID- 20047892
TI  - Neuroprotection Offered by Majun Khadar, a Traditional Unani Medicine, during
      Cerebral Ischemic Damage in Rats.
AB  - Stroke results in damages to many biochemical, molecular and behavioral deficits.
      Present study provides evidence of the protective efficacy of a Unani herbal
      medicine, Majun Khadar (MK), against cerebral ischemia-induced behavioral
      dysfunctions and neurochemical alterations in the hippocampus (HIP). Transient
      focal cerebral ischemia was induced for 2 h followed by reperfusion for 22 h in a
      rat model. Rats were divided into four groups: sham, middle cerebral artery
      occluded (MCAO), drug sham (MK; 0.816 g kg(-1) orally for 15 days) and MK pre
      treated ischemic group (MK + MCAO). Levels of enzymatic and non-enzymatic
      antioxidants were estimated in HIP along with behavioral testing. MK pre
      treatment significantly (P < .05-.001) restored the activities of glutathione
      peroxidase (GP*), glutathione reductase (GR), glutathione S-transferase (GST) and
      decreased the level of lipid peroxidation (LPO) and H2O2 content in HIP in the MK
      + MCAO group which were severely altered in the MCAO group. The content of
      glutathione (GSH), total thiols (TT) and ascorbic acid (AsA) was significantly
      depleted in the MCAO group; pretreatment with MK was able to restore its levels.
      Also in the MK + MCAO group, significant (P < .5-.001) recovery in behavioral
      testing by rota rod and open-field activities was seen as compared with the MCAO
      group. MK alone did not show any change neither in the status of various
      antioxidants nor behavioral functions over sham values. Although detailed studies
      are required for the evaluation of exact neuroprotective mechanism of MK against
      cerebral ischemia these preliminary experimental findings conclude that MK
      exhibits neuroprotective effect in cerebral ischemia by potentiating the
      antioxidant defense system of the brain. 

PMID- 20047893
TI  - Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of
      Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine.
AB  - Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in
      traditional Chinese medicine (TCM), mainly characterized by tiredness,
      emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth.
      Currently, there is no available animal model which can reflect the clinical
      features of this syndrome. In the present paper, we observed the time-course
      changes of whole behavior, body weight, food intake, locomotive activity and
      electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks,
      and measured bleeding time at last according to the clinical features of DQYS and
      one key pathological factor. The results showed that the mice exposed to
      intermittent hypoxia for certain time presented lackluster hair, dull looking
      hair, resistance, attacking, body weight loss, food intake decline, locomotive
      activity decrease, heart rate quickening and T wave elevating, which were similar
      to the major clinical features of DQYS. Meanwhile, bleeding time shortening was
      also found, which was consistent with the clinical fact that DQYS often
      accompanied with blood stasis. The possible explanation was also outlined
      according to the available literature. Such findings suggested chronic
      intermittent hypoxia could induce similar symptoms and signs in mice accorded
      with the clinical features of DQYS, which provided a suitable animal model for
      evaluation of drugs for the treatment of this syndrome and further exploration of
      pathological process or correlation of the syndrome and related diseases. 

PMID- 20047894
TI  - Radium, telomeres, and ribosomes: glass ceilings break in Stockholm.

PMID- 20047895
TI  - A (musical) note on protein purification.

PMID- 20047896
TI  - Creatine kinases: a cornerstone for structural research in the phosphagen kinase
      family.

PMID- 20047897
TI  - Interaction of physostigmine and alfentanil in a human pain model.
AB  - BACKGROUND: Preclinical and clinical studies suggest an important role for
      cholinesterase inhibitors in pain therapy. The aim of this study was to examine
      the analgesic and antihyperalgesic properties of the cholinesterase inhibitor
      physostigmine and the opioid alfentanil, alone and in combination, in an
      experimental pain model in humans. METHODS: Twenty healthy volunteers were
      enrolled in this double-blind and placebo-controlled cross-over study.
      Transcutaneous electrical stimulation at high current densities induced
      spontaneous acute pain and stable areas of hyperalgesia for painful mechanical
      stimuli (pinprick-hyperalgesia). Pain intensities, measured on a numeric rating
      scale (NRS) from 0 to 10, and the extent of the hyperalgesic areas were assessed
      before, during, and 145 min after i.v. infusions of physostigmine (30 microg kg(
      1) in 15 min), alfentanil (20 microg kg(-1) in 2 min), the combination of the
      same doses of both drugs, or saline 0.9%. The type of interaction was determined
      by fitting an interaction model to the data. RESULTS: Starting from a baseline
      value of NRS=6, the maximum reduction of pain intensity was 50.4 (sd 22.3) %
      after alfentanil, 35.4 (20.0) % after physostigmine, and 60.4 (17.1) % after the
      combination. The hyperalgesic areas were reduced by 53.8 (33.2) %, 47.0 (26.3) %,
      and 54.8 (33.2) %, respectively. The data were best described by a model assuming
      an infra-additive interaction for analgesic and antihyperalgesic effects.
      CONCLUSIONS: Physostigmine and alfentanil showed distinct effects on pain and
      hyperalgesia in a human pain model. The interaction of both drugs was found to be
      infra-additive.

PMID- 20047898
TI  - Urgent surgery in patients with a recently implanted coronary drug-eluting stent:
      a phase II study of 'bridging' antiplatelet therapy with tirofiban during
      temporary withdrawal of clopidogrel.
AB  - BACKGROUND: Patients with a recently implanted coronary drug-eluting stent (DES)
      who need urgent surgery are at increased risk of surgical bleeding unless
      clopidogrel is discontinued beforehand, but clopidogrel discontinuation has been
      associated with a high rate of adverse events due to stent thrombosis. This pilot
      study tested the hypothesis that the i.v. perioperative administration of the
      short-acting antiplatelet agent tirofiban allows the safe withdrawal of
      clopidogrel without increasing the rate of surgical bleeding. METHODS: Phase II
      study with a Simon two-stage design. RESULTS: Thirty patients with a recently
      implanted DES [median (range) 4 (1-12) months] and high-risk characteristics for
      stent thrombosis underwent urgent major surgery or eye surgery. Clopidogrel was
      to be withdrawn 5 days before surgery, and tirofiban started 24 h later,
      continued until 4 h before surgery, and resumed 2 h after surgery until oral
      clopidogrel was resumed. The use of aspirin was decided by the surgeon. There
      were no cases of death, myocardial infarction, stent thrombosis, or surgical re
      exploration due to bleeding during the index admission, with a risk estimate of 0
      11.6% (one-tail 97.5% CI). There was one case of thrombolysis in myocardial
      infarction (TIMI) major and one of TIMI minor bleeding in the postoperative
      phase; another four patients were transfused without meeting the TIMI criteria
      for major or minor bleeding. CONCLUSIONS: In patients with a recently implanted
      DES and high-risk characteristics for stent thrombosis needing urgent surgery, a
      'bridging strategy' using i.v. tirofiban may allow temporary withdrawal of oral
      clopidogrel without increasing the risk of bleeding.

PMID- 20047899
TI  - Pharmacological prevention of sevoflurane- and desflurane-related emergence
      agitation in children: a meta-analysis of published studies.
AB  - BACKGROUND: Emergence agitation (EA) in children is increased after sevoflurane
      anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of
      this study was to provide a meta-analysis of the studies of the pharmacological
      prevention of EA in children. METHODS: A comprehensive literature search was
      conducted to identify clinical trials that focused on the prevention of EA in
      children anaesthetized with sevoflurane, desflurane, or both. The data from each
      trial were combined using the Mantel-Haenszel model to calculate the pooled odds
      ratio (OR) and 95% confidence interval. I(2) statistics were used to assess
      statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess
      bias. RESULTS: Thirty-seven articles were found which included a total of 1695
      patients in the intervention groups and 1477 in the control ones. Midazolam and
      5HT(3) inhibitors were not found to have a protective effect against EA [OR=0.88
      (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21
      (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], alpha(2)-adrenoceptors [OR=0.23
      (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia
      [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup
      analysis according to the peroperative analgesia given does not affect the
      results. CONCLUSIONS: This meta-analysis found that propofol, ketamine, fentanyl,
      and preoperative analgesia had a prophylactic effect in preventing EA. The
      analgesic properties of these drugs do not seem to have a role in this effect.

PMID- 20047900
TI  - Intra-cerebral injection of neuromyelitis optica immunoglobulin G and human
      complement produces neuromyelitis optica lesions in mice.
AB  - Neuromyelitis optica is an inflammatory demyelinating disease of the central
      nervous system associated with autoantibodies against the glial water channel
      protein aquaporin-4. It has recently been reported that immunoglobulin from
      neuromyelitis optica patients injected peripherally does not cause lesions in
      naive rats, but only when pre-existing central nervous system inflammation is
      present. Here, we investigated whether immunoglobulin G from aquaporin-4
      autoantibody-positive neuromyelitis optica patients has the potential to damage
      the central nervous system either alone or in the presence of human complement.
      Immunoglobulin G from neuromyelitis optica patients did not activate mouse
      complement and was not pathogenic when injected into mouse brain. However, co
      injection of immunoglobulin G from neuromyelitis optica patients with human
      complement produced neuromyelitis optica-like lesions in mice. Within 12 h of co
      injecting immunoglobulin G from neuromyelitis optica patients and human
      complement, there was a striking loss of aquaporin-4 expression, glial cell
      oedema, myelin breakdown and axonal injury, but little intra-parenchymal
      inflammation. At 7 days, there was extensive inflammatory cell infiltration,
      perivascular deposition of activated complement components, extensive
      demyelination, loss of aquaporin-4 expression, loss of reactive astrocytes and
      neuronal cell death. In behavioural studies, mice injected with immunoglobulin G
      from neuromyelitis optica patients and human complement into the right hemisphere
      preferentially turned to the right at 7 days. No brain inflammation,
      demyelination or right-turning behaviour was seen in wild-type mice that received
      immunoglobulin G from non-neuromyelitis optica patients with human complement, or
      in aquaporin-4-null mice that received immunoglobulin G from neuromyelitis optica
      patients with human complement. We conclude that co-injection of immunoglobulin G
      from neuromyelitis optica patients with human complement reproduces the key
      histological features of neuromyelitis optica and that aquaporin-4 is necessary
      and sufficient for immunoglobulin G from neuromyelitis optica patients to exert
      its effect. In our mouse model, immunoglobulin G from neuromyelitis optica
      patients does not require pre-existing central nervous system inflammation to
      produce lesions.

PMID- 20047901
TI  - Schwann cell p75NTR prevents spontaneous sensory reinnervation of the adult
      spinal cord.
AB  - Schwann cells are attractive candidates for repair of the injured spinal cord.
      Transplanted Schwann cells are permissive to regeneration, but their ability to
      promote regeneration into distal spinal cord remains weak despite their
      production of growth-promoting neurotrophins. Schwann cell activation such as
      that which accompanies peripheral nerve injury results in massive upregulation of
      the p75(NTR) pan-neurotrophin-receptor. Here we test the hypothesis that this
      p75(NTR) upregulation following dorsal root injury limits availability of
      endogenous neurotrophin to axons and restricts regeneration of injured axons into
      the spinal cord. We injured dorsal roots (fourth cervical to second thoracic) in
      mice lacking the neurotrophin-binding domain of p75(NTR) and in wild-type
      littermates. Axonal regeneration was assessed by selective tracing of
      neurotrophin-responsive and non-responsive dorsal root ganglion neurons.
      Functional reinnervation of the spinal cord was assessed in behavioural
      experiments and via Fos immunohistochemistry following formalin injection into
      the forepaw. We also measured levels of nerve growth factor and neurotrophin-3
      following nerve injury in knockout and wild-type mice, and used Trk-Fc receptor
      chimeras to block nerve growth factor and neurotrophin-3 signalling in dorsal
      root ganglion/Schwann cell co-cultures and following dorsal root injury in vivo.
      The roles of neuronal and glial p75(NTR) were assessed in transplant experiments
      in vivo and in co-cultures. We found that nerve growth factor and neurotrophin-3
      responsive axons regenerated into the spinal cord of p75(NTR) knockout mice where
      they made functional connections with dorsal horn neurons. Despite equivalent
      levels of nerve growth factor and neurotrophin-3 in wild-type and knockout mice,
      successful regeneration in knockouts was neurotrophin-dependent. Transplantation
      of p75(-/-) neurons into a wild-type environment, p75(-/-) peripheral nerve
      grafts into the injured p75(+/+) spinal cord, and dissociated sensory
      neuron/Schwann cell co-cultures showed that the absence of p75(NTR) from glia,
      not from neurons, promotes regeneration. These findings indicate that Schwann
      cell p75(NTR) restricts neurotrophin availability to the extent that it prevents
      spontaneous sensory axon regeneration into the spinal cord. The implication is
      that inactivating p75(NTR) in Schwann (or olfactory ensheathing) cells may enable
      axons to grow beyond transplants, improving the outcome of spinal cord injury.

PMID- 20047902
TI  - A clear case of possession. Editorial.

PMID- 20047903
TI  - Copy number variants--an unexpected risk factor for the idiopathic generalized
      epilepsies.

PMID- 20047905
TI  - The ATTRACT trial: rationale for early intervention for iliofemoral DVT.
AB  - The management of acute deep vein thrombosis (DVT) by medical therapy with
      anticoagulation has long been supported by evidence-based clinical practice
      guidelines outlined in the American College of Chest Physicians supplement. Early
      thrombus removal in patients with iliofemoral DVT has been reported to lead to
      improved venous valve function, improved quality of life, and decreased incidence
      of postthrombotic syndrome over anticoagulation alone. The ATTRACT trial will
      randomize patients to medical management with standard anticoagulation versus
      catheter-directed thrombolysis in addition to standard anticoagulation after
      stratification to iliofemoral versus femoropopliteal DVT in order to determine
      the primary outcome of postthrombotic syndrome over a 24-month follow-up.

PMID- 20047904
TI  - Beneficial effects of secretory leukocyte protease inhibitor after spinal cord
      injury.
AB  - Secretory leukocyte protease inhibitor is a serine protease inhibitor produced by
      various cell types, including neutrophils and activated macrophages, and has anti
      inflammatory properties. It has been shown to promote wound healing in the skin
      and other non-neural tissues, however, its role in central nervous system injury
      was not known. We now report a beneficial role for secretory leukocyte protease
      inhibitor after spinal cord injury. After spinal cord contusion injury in mice,
      secretory leukocyte protease inhibitor is expressed primarily by astrocytes and
      neutrophils but not macrophages. We show, using transgenic mice over-expressing
      secretory leukocyte protease inhibitor, that this molecule has an early
      protective effect after spinal cord contusion injury. Furthermore, wild-type mice
      treated for the first week after spinal cord contusion injury with recombinant
      secretory leukocyte protease inhibitor exhibit sustained improvement in locomotor
      control and reduced secondary tissue damage. Recombinant secretory leukocyte
      protease inhibitor injected intraperitoneally localizes to the nucleus of
      circulating leukocytes, is detected in the injured spinal cord, reduces
      activation of nuclear factor-kappaB and expression of tumour necrosis factor
      alpha. Administration of recombinant secretory leukocyte protease inhibitor might
      therefore be useful for the treatment of acute spinal cord injury.

PMID- 20047906
TI  - Superdormant spores of bacillus species germinate normally with high pressure,
      peptidoglycan fragments, and bryostatin.
AB  - Superdormant spores of Bacillus cereus and Bacillus subtilis germinated just as
      well as dormant spores with pressures of 150 or 500 MPa and with or without heat
      activation. Superdormant B. subtilis spores also germinated as well as dormant
      spores with peptidoglycan fragments or bryostatin, a Ser/Thr protein kinase
      activator.

PMID- 20047907
TI  - Complete genome sequence of Staphylococcus lugdunensis strain HKU09-01.
AB  - Staphylococcus lugdunensis is a member of the coagulase-negative staphylococci
      and commonly found as part of the human skin flora. It is a significant cause of
      catheter-related bacteremia and also causes serious infections like native valve
      endocarditis in previously healthy individuals. We report the complete genome
      sequence of this medically important bacterium.

PMID- 20047908
TI  - ATP-dependent carboxylation of acetophenone by a novel type of carboxylase.
AB  - Anaerobic ethylbenzene metabolism in the betaproteobacterium Aromatoleum
      aromaticum is initiated by anaerobic oxidation to acetophenone via (S)-1
      phenylethanol. The subsequent carboxylation of acetophenone to benzoylacetate is
      catalyzed by an acetophenone-induced enzyme, which has been purified and studied.
      The same enzyme is involved in acetophenone metabolism in the absence of
      ethylbenzene. Acetophenone carboxylase consists of five subunits with molecular
      masses of 70, 15, 87, 75, and 34 kDa, whose genes (apcABCDE) form an apparent
      operon. The enzyme is synthesized at high levels in cells grown on ethylbenzene
      or acetophenone, but not in cells grown on benzoate. During purification,
      acetophenone carboxylase dissociates into inactive subcomplexes consisting of the
      70-, 15-, 87-, and 75-kDa subunits (apcABCD gene products) and the 34-kDa subunit
      (apcE gene product), respectively. Acetophenone carboxylase activity was restored
      by mixing the purified subcomplexes. The enzyme contains 1 Zn(2+) ion per
      alphabetagammadelta core complex and is dependent on the presence of Mg(2+) or
      Mn(2+). In spite of the presence of Zn in the enzyme, it is strongly inhibited by
      Zn(2+) ions. Carboxylation of acetophenone is dependent on ATP hydrolysis to ADP
      and P(i), exhibiting a stoichiometry of 2 mol ATP per mol acetophenone
      carboxylated. The enzyme shows uncoupled ATPase activity with either bicarbonate
      or acetophenone in the absence of the second substrate. These observations
      indicate that both substrates may be phosphorylated, which is consistent with
      isotope exchange activity observed with deuterated acetophenone and inhibition by
      carbamoylphosphate, a structural analogue of carboxyphosphate. A potential
      mechanism of ATP-dependent acetophenone carboxylation is suggested.

PMID- 20047909
TI  - The apparent malate synthase activity of Rhodobacter sphaeroides is due to two
      paralogous enzymes, (3S)-Malyl-coenzyme A (CoA)/{beta}-methylmalyl-CoA lyase and
      (3S)- Malyl-CoA thioesterase.
AB  - Assimilation of acetyl coenzyme A (acetyl-CoA) is an essential process in many
      bacteria that proceeds via the glyoxylate cycle or the ethylmalonyl-CoA pathway.
      In both assimilation strategies, one of the final products is malate that is
      formed by the condensation of acetyl-CoA with glyoxylate. In the glyoxylate cycle
      this reaction is catalyzed by malate synthase, whereas in the ethylmalonyl-CoA
      pathway the reaction is separated into two proteins: malyl-CoA lyase, a well
      known enzyme catalyzing the Claisen condensation of acetyl-CoA with glyoxylate
      and yielding malyl-CoA, and an unidentified malyl-CoA thioesterase that
      hydrolyzes malyl-CoA into malate and CoA. In this study the roles of Mcl1 and
      Mcl2, two malyl-CoA lyase homologs in Rhodobacter sphaeroides, were investigated
      by gene inactivation and biochemical studies. Mcl1 is a true (3S)-malyl-CoA lyase
      operating in the ethylmalonyl-CoA pathway. Notably, Mcl1 is a promiscuous enzyme
      and catalyzes not only the condensation of acetyl-CoA and glyoxylate but also the
      cleavage of beta-methylmalyl-CoA into glyoxylate and propionyl-CoA during acetyl
      CoA assimilation. In contrast, Mcl2 was shown to be the sought (3S)-malyl-CoA
      thioesterase in the ethylmalonyl-CoA pathway, which specifically hydrolyzes (3S)
      malyl-CoA but does not use beta-methylmalyl-CoA or catalyze a lyase or
      condensation reaction. The identification of Mcl2 as thioesterase extends the
      enzyme functions of malyl-CoA lyase homologs that have been known only as
      "Claisen condensation" enzymes so far. Mcl1 and Mcl2 are both related to malate
      synthase, an enzyme which catalyzes both a Claisen condensation and thioester
      hydrolysis reaction.

PMID- 20047910
TI  - The ferrichrome uptake pathway in Pseudomonas aeruginosa involves an iron release
      mechanism with acylation of the siderophore and recycling of the modified
      desferrichrome.
AB  - The uptake of iron into Pseudomonas aeruginosa is mediated by two major
      siderophores produced by the bacterium, pyoverdine and pyochelin. The bacterium
      is also able of utilize several heterologous siderophores of bacterial or fungal
      origin. In this work, we have investigated the iron uptake in P. aeruginosa PAO1
      by the heterologous ferrichrome siderophore. (55)Fe uptake assays showed that
      ferrichrome is transported across the outer membrane primarily (80%) by the FiuA
      receptor and to a lesser extent (20%) by a secondary transporter. Moreover, we
      demonstrate that like in the uptake of ferripyoverdine and ferripyochelin, the
      energy required for both pathways of ferrichrome uptake is provided by the inner
      membrane protein TonB1. Desferrichrome-(55)Fe uptake in P. aeruginosa was also
      dependent on the expression of the permease FiuB, suggesting that this protein is
      the inner membrane transporter of the ferrisiderophore. A biomimetic fluorescent
      analogue of ferrichrome, RL1194, was used in vivo to monitor the kinetics of iron
      release from ferrichrome in P. aeruginosa in real time. This dissociation
      involves acylation of ferrichrome and its biomimetic analogue RL1194 and
      recycling of both modified siderophores into the extracellular medium. FiuC, an N
      acetyltransferase, is certainly involved in this mechanism of iron release, since
      its mutation abolished desferrichrome-(55)Fe uptake. The acetylated derivative
      reacts with iron in the extracellular medium and is able to be taken up again by
      the cells. All these observations are discussed in light of the current knowledge
      concerning ferrichrome uptake in P. aeruginosa and in Escherichia coli.

PMID- 20047911
TI  - In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246.
AB  - Human cytomegalovirus (HCMV) remains a serious threat for immunocompromised
      individuals, including transplant recipients and newborns. To date, all drugs
      licensed for the treatment of HCMV infection and disease target the viral DNA
      polymerase. Although these drugs are effective, several drawbacks are associated
      with their use, including toxicity and emergence of drug resistance. Hence, new
      and improved antivirals with novel molecular targets are urgently needed. Here we
      report on the antiviral properties of AIC246, a representative of a novel class
      of low-molecular-weight compounds that is currently undergoing clinical phase II
      studies. The anti-HCMV activity of AIC246 was evaluated in vitro and in vivo
      using various cell culture assays and an engineered mouse xenograft model. In
      addition, antiviral properties of the drug were characterized in comparison to
      the current gold standard ganciclovir. We demonstrate that AIC246 exhibits
      excellent in vitro inhibitory activity against HCMV laboratory strains and
      clinical isolates, retains activity against ganciclovir-resistant viruses, is
      well tolerated in different cell types (median selectivity index, 18,000), and
      exerts a potent in vivo efficacy in a mouse xenograft model. Moreover, we show
      that the antiviral block induced by AIC246 is reversible and the efficacy of the
      drug is not significantly affected by cell culture variations such as cell type
      or multiplicity of infection. Finally, initial mode-of-action analyses reveal
      that AIC246 targets a process in the viral replication cycle that occurs later
      than DNA synthesis. Thus, AIC246 acts via a mode of action that differs from that
      of polymerase inhibitors like ganciclovir.

PMID- 20047912
TI  - Activity of dalbavancin against Bacillus anthracis in vitro and in a mouse
      inhalation anthrax model.
AB  - Bacillus anthracis, the causative agent of anthrax, can produce fatal disease
      when it is inhaled or ingested by humans. Dalbavancin, a novel, semisynthetic
      lipoglycopeptide, has potent activity, greater than that of vancomycin, against
      Gram-positive bacteria and a half-life in humans that supports once-weekly
      dosing. Dalbavancin demonstrated potent in vitro activity against B. anthracis
      (MIC range, < or =0.03 to 0.5 mg/liter; MIC(50) and MIC(90), 0.06 and 0.25
      mg/liter, respectively), which led us to test its efficacy in a murine inhalation
      anthrax model. The peak concentrations of dalbavancin in mouse plasma after the
      administration of single intraperitoneal doses of 5 and 20 mg/kg of body weight
      were 15 and 71 mg/kg, respectively. At 20 mg/kg, the dalbavancin activity was
      detectable for 6 days after administration (terminal half-life, 53 h), indicating
      that long intervals between doses were feasible. The mice were challenged with 50
      to 100 times the median lethal dose of the Ames strain of B. anthracis, an
      inoculum that kills untreated animals within 4 days. The efficacy of dalbavancin
      was 80 to 100%, as determined by the rate of survival at 42 days, when treatment
      was initiated 24 h postchallenge with regimens of 15 to 120 mg/kg every 36 h
      (q36h) or 30 to 240 mg/kg every 72 h (q72h). A regimen of ciprofloxacin known to
      protect 100% of animals was tested in parallel. Delayed dalbavancin treatment
      (beginning 36 or 48 h postchallenge) with 60 mg/kg q36h or 120 mg/kg q72h still
      provided 70 to 100% survival. The low MICs and long duration of efficacy in vivo
      suggest that dalbavancin may have potential as an alternative treatment or for
      the prophylaxis of B. anthracis infections.

PMID- 20047913
TI  - High prevalence of ST131 isolates producing CTX-M-15 and CTX-M-14 among extended
      spectrum-beta-lactamase-producing Escherichia coli isolates from Canada.
AB  - Phenotypic and genotypic methods were used to characterize extended-spectrum-beta
      lactamase (ESBL)-producing Escherichia coli isolated in 2007 from 11 different
      Canadian medical centers. Of the 209 ESBL-producing E. coli isolates tested, 148
      (71%) produced CTX-M-15, 17 (8%) produced CTX-M-14, 5 (2%) produced CTX-M-3, and
      1 produced CTX-M-27. Overall, 96 (46%) of the ESBL producers belonged to clonal
      complex ST131, with the highest prevalence in Brampton, Calgary, and Winnipeg.
      ST131 is an important cause of community onset urinary tract infections due to
      ESBL-producing E. coli across Canada.

PMID- 20047915
TI  - Full Resistance and decreased susceptibility to carbapenems in IMP-13-producing
      Pseudomonas aeruginosa isolates from an outbreak.

PMID- 20047914
TI  - Efficacy of rifampin and its combinations with imipenem, sulbactam, and colistin
      in experimental models of infection caused by imipenem-resistant Acinetobacter
      baumannii.
AB  - There are currently no defined optimal therapies available for multidrug
      resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of
      rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A.
      baumannii in experimental pneumonia and meningitis models. The bactericidal in
      vitro activities of rifampin, imipenem, sulbactam, colistin, and their
      combinations were tested using time-kill curves. Murine pneumonia and rabbit
      meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs
      for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter,
      respectively). Mice were treated with the four antimicrobials and their
      combinations. For the meningitis model, the efficacies of colistin, rifampin and
      its combinations with imipenem, sulbactam, or colistin, and of imipenem plus
      sulbactam were assayed. In the pneumonia model, compared to the control group,
      (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin,
      (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung
      bacterial concentrations (10.6 +/- 0.27 [controls] versus 3.05 +/- 1.91, 2.07 +/-
      1.82, 2.41 +/- 1.37, 3.4 +/- 3.07, 6.82 +/- 3.4, and 4.22 +/- 2.72 log(10) CFU/g,
      respectively [means +/- standard deviations]), increased sterile blood cultures
      (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0%
      versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model
      rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial
      counts (-2.6 and -4.4 log(10) CFU/ml). Rifampin in monotherapy or with imipenem,
      sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental
      models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for
      combined treatment when using rifampin.

PMID- 20047916
TI  - Effectiveness of hand sanitizers with and without organic acids for removal of
      rhinovirus from hands.
AB  - These studies evaluated the effectiveness of ethanol hand sanitizers with or
      without organic acids to remove detectable rhinovirus from the hands and prevent
      experimental rhinovirus infection. Ethanol hand sanitizers were significantly
      more effective than hand washing with soap and water. The addition of organic
      acids to the ethanol provided residual virucidal activity that persisted for at
      least 4 h. Whether these treatments will reduce rhinovirus infection in the
      natural setting remains to be determined.

PMID- 20047917
TI  - Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows
      superior anti-influenza virus activity after a single administration.
AB  - Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate
      (Tamiflu), have been licensed for use for the treatment and prophylaxis of
      influenza. We have reported on laninamivir (code name, R-125489), a novel
      neuraminidase inhibitor, and have discovered that the laninamivir prodrug CS-8958
      worked as a long-acting neuraminidase inhibitor in a mouse influenza virus
      infection model when it is intranasally administered. In this study, CS-8958 was
      administered just once 7 days before infection and showed significant efficacy in
      vivo. The efficacy of a single administration of CS-8958 after viral infection
      was then compared with that of repeated administrations of oseltamivir phosphate
      or zanamivir in mice and ferrets. CS-8958 showed efficacy superior or similar to
      the efficacies of the two licensed NA inhibitors. CS-8958 also significantly
      reduced the titers of an oseltamivir-resistant H1N1 virus with a neuraminidase
      H274Y substitution in a mouse infection model. These results suggest that since
      CS-8958 is characteristically long lasting in the lungs, it may be ideal for the
      prophylaxis and treatment of influenza.

PMID- 20047918
TI  - Antibacterial activity of N-pentylpantothenamide is due to inhibition of coenzyme
      a synthesis.
AB  - Growth inhibition by the pantothenate analog N-pentylpantothenamide (N5-Pan) has
      been attributed to the accumulation of acyl carrier protein carrying a prosthetic
      group modified by incorporation of N5-Pan. This was attributed to an inability of
      the AcpH acyl carrier protein phosphodiesterase to cleave the N5-Pan-modified
      prosthetic group from the protein moiety. We report that AcpH readily removes the
      N5-Pan-modified prosthetic group both in vivo and in vitro and show that N5-Pan
      blocks coenzyme A synthesis.

PMID- 20047919
TI  - Evaluation of new thiazolide/thiadiazolide derivatives reveals nitro group
      independent efficacy against in vitro development of Cryptosporidium parvum.
AB  - Thirty-nine new thiazolide/thiadiazolide compounds were compared with the
      nitrothiazole nitazoxanide for activity against Cryptosporidium parvum
      development in HCT-8 cells. Twenty-seven agents exerted > or =90% inhibition.
      Agents with a lower 50% inhibitory concentration (IC(50)) than nitazoxanide were
      either NO(2) or halogen 5 substituted on the thiazole moiety. Other 5
      substitutions such as methyl, C(3)H(7), C(6)H(11), H, SO(2)CH(3), and SCH(3)
      negatively impacted activity. Five-substituted deacetylated analogues exhibited
      higher IC(50)s than their acetylated counterparts. Halogeno
      thiazolide/thiadiazolides may provide valuable nitro-free alternatives to
      nitazoxanide.

PMID- 20047921
TI  - A conceptual framework for understanding interorganizational relationships
      between nursing homes and emergency departments: examples from the Canadian
      setting.
AB  - Nursing home residents who experience exacerbations of chronic health conditions
      or new illnesses must generally go to the emergency department for health care.
      This reliance on two distinct settings of care requires organizations to engage
      in an interorganizational relationship, which can be problematic, particularly
      when each organization has its own governing structures, policies, practices, and
      culture. Although it is widely acknowledged that interorganizational
      relationships can be the source of much frustration and conflict, little is known
      about their underpinnings. In this article, the authors draw on the literature to
      explore the interorganizational relationship that emerges each time a resident
      transfers between a nursing home and an emergency department in Canada. The
      authors apply this knowledge to develop a conceptual model that can be used to
      explore other interorganizational relationships that are formed when patients
      move between settings of care.

PMID- 20047920
TI  - Pradimicin S, a highly soluble nonpeptidic small-size carbohydrate-binding
      antibiotic, is an anti-HIV drug lead for both microbicidal and systemic use.
AB  - Pradimicin S (PRM-S) is a highly water-soluble, negatively charged derivative of
      the antibiotic pradimicin A (PRM-A) in which the terminal xylose moiety has been
      replaced by 3-sulfated glucose. PRM-S does not prevent human immunodeficiency
      virus (HIV) adsorption on CD4(+) T cells, but it blocks virus entry into its
      target cells. It inhibits a wide variety of HIV-1 laboratory strains and clinical
      isolates, HIV-2, and simian immunodeficiency virus (SIV) in various cell culture
      systems (50% and 90% effective concentrations [EC(50)s and EC(90)s] invariably in
      the lower micromolar range). PRM-S inhibits syncytium formation between
      persistently HIV-1- and SIV-infected cells and uninfected CD4(+) T lymphocytes,
      and prevents dendritic cell-specific intercellular adhesion molecule-3-grabbing
      nonintegrin (DC-SIGN)-mediated HIV-1 and SIV capture and subsequent virus
      transmission to CD4(+) T cells. Surface plasmon resonance (SPR) studies revealed
      that PRM-S strongly binds to gp120 in a Ca(2+)-dependent manner at an affinity
      constant (K(D)) in the higher nanomolar range. Its anti-HIV activity and HIV-1
      gp120-binding properties can be dose-dependently reversed in the presence of an
      (alpha-1,2)mannose trimer. Dose-escalating exposure of HIV-1-infected cells to
      PRM-S eventually led to the isolation of mutant virus strains that had various
      deleted N-glycosylation sites in the envelope gp120 with a strong preference for
      the deletion of the high-mannose-type glycans. Genotypic resistance development
      occurred slowly, and significant phenotypic resistance occurred only after the
      sequential appearance of up to six mutations in gp120, pointing to a high genetic
      barrier of PRM-S. The antibiotic is nontoxic against a variety of cell lines, is
      not mitogenic, and does not induce cytokines and chemokines in peripheral blood
      mononuclear cells as determined by the Bio-Plex human cytokine 27-plex assay. It
      proved stable at high temperature and low pH. Therefore, PRM-S may qualify as a
      potential anti-HIV drug candidate for further (pre)clinical studies, including
      its microbicidal use.

PMID- 20047922
TI  - An analysis of racial/ethnic pay disparities among hospital nurses in New York
      City.
AB  - Despite growing concern over cultural competence and diversity in the registered
      nursing (RN) workforce, minority RNs working in hospitals in New York City who
      were surveyed in 2007 earned less on average than their non-Hispanic White
      counterparts. Regression decomposition was applied to these data to investigate
      how much of the differential could be attributed to different characteristics of
      different racial/ethnic groups and how much could be attributed to differential
      valuation of characteristics between racial/ethnic groups. The earnings
      differential between Black/African American and non-Hispanic White RNs was about
      equally due to different characteristics and differential valuation of
      characteristics, but the earnings differentials between Hispanic/Latino RNs and
      non-Hispanic White RNs and between Asian/Pacific Islander RNs and non-Hispanic
      White RNs were about two-thirds due to different characteristics and one-third
      due to differential valuation of their characteristics. In particular, years of
      nursing experience did not translate into the same earnings advantages for
      minority RNs.

PMID- 20047923
TI  - Justice and impoverished women: the ethical implications of work-based welfare.
AB  - Current U.S. welfare policy, Temporary Assistance for Needy Families, requires
      impoverished people to work in order to receive welfare, and it limits cash
      support to 5 years. Most of the people who have used this program are single
      parent women, and a disturbing number have been terminated at 5 years, not having
      made a successful transition to work. The purpose of this longitudinal study was
      to explore the barriers to success and the social justice of the program from the
      perspective of single-parent women who were terminated. In all, 41 women were
      recruited through community-based purposive sampling, and the primary research
      methods were a qualitative, narrative interview approach and narrative analysis.
      Data from the semistructured interview guide are reported here. Findings describe
      health and socioeconomic burdens, and barriers that lie within the social policy.
      The study has ethical implications for nursing advocacy, and it informs nursing
      interventions for impoverished women and their families.

PMID- 20047924
TI  - Prospective evaluation of non-pharmacological treatment in vasovagal syncope.
AB  - AIMS: Initial treatment of vasovagal syncope (VVS) consists of assuring an
      adequate fluid and salt intake, regular exercise and application of physical
      counterpressure manoeuvres. We examined the effects of this non-pharmacological
      treatment in patients with frequent recurrences. METHODS AND RESULTS: One hundred
      patients with > or =3 episodes of VVS in the 2 years prior to the start of the
      study openly received non-pharmacological treatment. We evaluated this treatment
      both with respect to syncopal recurrences, factors associated with recurrence,
      and quality of life (QoL). The median number of syncopal recurrences was lower in
      the first year of non-pharmacological treatment compared with the last year
      before treatment (median 0 vs. 3; P < 0.001), but 49% of patients experienced at
      least one recurrence. In multivariable analysis, a higher syncope burden prior to
      inclusion was significantly associated with syncopal recurrence. Disease-specific
      QoL improved over time, with larger improvements for patients with more reduction
      in syncope burden. CONCLUSION: In patients with frequent recurrences of VVS, non
      pharmacological treatment has a beneficial effect on both syncopal recurrence and
      QoL, but nearly half of these patients still experience episodes of syncope.

PMID- 20047925
TI  - Does defibrillation threshold increase as left ventricular ejection fraction
      decreases?
AB  - AIMS: Advanced cardiac disease, entailing more hypertrophy, fibrosis, scarring,
      dilatation and conduction delays, poses the question of whether defibrillation
      thresholds (DFTs) increase as left ventricular ejection fraction (LVEF)
      decreases. This question has been approached indirectly or insufficiently in
      previous studies. In this study we add and expand on our previous work,
      stratifying DFT for various LVEF ranges. METHODS AND RESULTS: This retrospective
      analysis included DFT data from three acute, multicentre, randomized studies that
      included 230 ICD/CRT-D patients. All DFTs were obtained with the SVC coil turned
      ON and with pulse-width optimized waveforms based on a 3.5 ms membrane time
      constant. As the LVEF decreased, DFT estimates increased from 395.2 +/- 115 V for
      LVEF > or = 46% to 425.8 +/- 117.6 V for LVEF < or = 25%. However, these changes
      in DFT estimates were very minor and not statistically significant. Only 3% of
      the patients in this population had an elevated DFT of >20 J. CONCLUSION: This
      analysis shows that over a very broad range of LVEF, DFT changes minimally
      (approximately 1 J), if at all. Our results are consistent with previous studies
      that demonstrated no difference in the DFT estimates: (a) between patient groups
      receiving ICD (typically higher LVEF) vs. CRT-D (typically lower LVEF) and (b)
      between patient groups receiving a device for primary prevention indications
      (typically lower LVEF) vs. secondary prevention indications (typically higher
      LVEF).

PMID- 20047926
TI  - Jugular pacing lead extraction with laser sheath: a case report.
AB  - Over the past 20 years, the number of patients with pacemakers (PM) or
      implantable cardioverter defibrillators has risen markedly; consequently, an
      increasing number of lead-removal procedures have become necessary. A 64-year-old
      woman presenting with an infected device pocket and positive bacterial cultures
      (Staphylococcus aureus) was admitted to our department for lead removal; in 1991,
      she underwent VVI PM implantation for atrioventricular II degree Mobitz 1 block,
      and a unipolar lead was introduced via the left jugular vein. The procedure was
      performed in our Electrophysiology Lab with a cardiac surgeon on standby, using
      an excimer laser system emitting the energy at the tip of a flexible, fibre-optic
      12 F sheath, developed by Spectranetics, Inc., Colorado Springs, CO, USA.

PMID- 20047927
TI  - Intrathoracic impedance and pulmonary wedge pressure for the detection of heart
      failure deterioration.
AB  - AIMS: The aims of this analysis were to assess the agreement between implantable
      defibrillator (ICD)-measured intrathoracic impedance and pulmonary capillary
      wedge pressure (PCWP) collected during long-term follow-up, as well as to
      evaluate whether PCWP measures may improve the performance of the impedance
      detection algorithm in predicting heart failure (HF) worsening. METHODS AND
      RESULTS: We studied 23 HF patients implanted with an ICD capable of intrathoracic
      impedance measurement and alerting for fluid accumulation diagnosis. At regular
      follow-up and at visits for HF decompensation or device alert, clinical status
      was assessed and PCWP was non-invasively estimated with a validated echo-Doppler
      method. During 23 +/- 11 months, 45 paired assessments of impedance and PCWP were
      performed. The Kappa analysis revealed good agreement between impedance and PCWP
      (k = 0.701, SE 0.113, P < 0.001). Moreover, PCWP estimations and the paired
      values of the impedance fluid index resulted significantly correlated (r = 0.677,
      P < 0.001). The impedance-alert detected clinical HF deterioration with 92%
      sensitivity and 69% positive predictive value. The combined finding of decreased
      impedance and increased PCWP resulted in enhanced positive predictive value (92%)
      and no change in sensitivity (92%). CONCLUSION: These data confirm the inverse
      correlation between impedance and PCWP at long-term follow-up and suggest the
      potential clinical value of a combined impedance and pressure assessment for the
      improved detection of HF deterioration.

PMID- 20047928
TI  - Changes in P-wave area and P-wave duration after circumferential pulmonary vein
      isolation.
AB  - AIMS: The effect of circumferential pulmonary vein isolation (CPVI) on P-wave
      characteristics is not clear. We used the signal-averaged (SA) electrocardiogram
      (ECG) and the ECG derived vector cardiogram (dVCG) to study the influence of CPVI
      on P-wave duration (PWD) and P-wave area (PWA) and studied whether changes were
      associated with successful outcome after initial CPVI. METHODS AND RESULTS:
      Thirty-nine patients (56 +/- 10 years, 72% males) underwent CPVI for paroxysmal
      or persistent atrial fibrillation (AF). For each patient, an ECG recording was
      taken at the start and end of the ablation procedure. dVCG was derived using the
      inverse Dower transform. PWD was defined by manual annotation of earliest onset
      and latest offset of the SA-P-wave. PWA was calculated as the area under the SA
      ECG curve averaged for the 12 ECG leads (PWA-ECG) and SA-dVCG curve (PWA-dVCG).
      Successful outcome after CPVI was defined as freedom from symptomatic and
      asymptomatic AF at the end of follow-up (11 +/- 5 months). Average PWD decreased
      from 132 +/- 14 to 126 +/- 16 ms (P < 0.01). PWA-ECG and PWA-dVCG decreased
      markedly from 4.64 +/- 1.40 to 3.65 +/- 1.61 mVms (P < 0.001) and from 4.27 +/-
      1.66 to 2.48 +/- 1.59 mVms (P < 0.001). Parameters of PWA were not different
      between successes (n = 31) and failures (n = 8). In contrast, PWD after ablation
      was significantly shorter in patients with successful outcome (123 +/- 16 vs. 135
      +/- 11 ms, P < 0.05). CONCLUSION: (i) CPVI results in a modest but significant
      shortening in PWD and a marked decrease in PWA. (ii) PWD was significantly
      shorter in cases of successful outcome after CPVI.

PMID- 20047929
TI  - Multimodality imaging of a pacemaker lead crossing a primum atrial septal defect.

PMID- 20047930
TI  - Osteosclerotic myeloma with POEMS syndrome.

PMID- 20047931
TI  - Intermittent cardiac shunt mimicking pulmonary embolism and COPD.

PMID- 20047932
TI  - European Public Health Association * President's column: 2010 and forward * EUPHA
      office column: going from Lodz 2009 to Amsterdam 2010.

PMID- 20047933
TI  - Social inequities in environmental risks associated with housing and residential
      location--a review of evidence.
AB  - BACKGROUND: Housing conditions and environmental quality of residential areas are
      differentially distributed in the population. Less affluent population groups are
      more often affected by inadequate housing conditions and higher environmental
      burden in their residential neighbourhoods. A synthesis of the dispersed evidence
      on health-related housing characteristics and social status is needed to provide
      support for housing policies addressing social inequities. METHODS: The
      literature on social inequities and environmental risks related to housing and
      residential location was searched in health, environmental and geographical
      databases and reviewed to summarize the evidence. Household-level socio-economic
      status and income were considered as indicators of social status. The review was
      limited to European evidence. RESULTS: Adequate studies were only available for
      few countries. Most studies identified the less affluent population groups as
      most exposed to environmental risks in the place of residence. Inequities were
      reported for risks experienced within the dwelling (such as exposure to dampness,
      chemical contamination, noise, temperature problems and poor sanitation) and
      related to residential location (neighbourhood quality, traffic-related
      pollution, proximity to pollution sites). Increased exposure to environmental
      risks within more affluent population groups was rarely identified. CONCLUSIONS:
      The review indicates that social status and especially low income are strongly
      associated with increased exposure to environmental risks in the private home or
      related to residential location. However, due to the methodological variety of
      the available studies and the lack of data for many countries, it is not possible
      to provide a general assessment of the magnitude of inequity in Europe at the
      present time.

PMID- 20047934
TI  - Controlling arterial hypertension in the French West Indies: a separate strategy
      for women?
AB  - BACKGROUND: To estimate the prevalence, awareness and treatment of arterial
      hypertension in Guadeloupe. METHODS: In 2007, a cross-sectional study of 1005 men
      and women (54%) aged 25-74 years from Guadeloupe, stratified by sex, age and
      region was set up to determine the prevalence of hypertension. Blood pressure
      (BP) was measured using an automated device and hypertension was defined as
      having a mean BP >= 140/90 mmHg or receiving drug treatment. RESULTS: The
      prevalence of hypertension was 33% for men and 37% for women (P = 0.62). Among
      hypertensive respondents, 57% of men and 80% of women were aware of being
      hypertensive (P < 0.001). BP was controlled for 22 and 44% of hypertensive men
      and women, respectively (P < 0.001). Compared with men (14%), 31% of women were
      obese (>= 30 kg/m2). In multivariate analyses, body mass index (BMI) was
      associated with hypertension in both sexes after controlling for age, occupation,
      education, alcohol consumption, smoking status and physical activity. Compared
      with subjects with a normal BMI, obese men were three times [odds ratio (OR) =
      3.4, 95% confidence interval (CI) = 1.8-6.6 P < 0.001] and obese women two times
      more likely (OR = 2.0, 95% CI = 1.2-3.4, P = 0.017) to be hypertensive. In women,
      low educational attainment was also associated with hypertension (OR = 2.1 95% CI
      = 1.1-4.0, P = 0.030) and mean diastolic BP decreased as educational attainment
      increased after controlling for confounders (F = 5.0, df 2, P = 0.007).
      CONCLUSIONS: Strong gender disparities in hypertension were identified. Separate
      strategies in addressing hypertension in men and women are needed, with an
      improvement in men's follow-up care and health promotion, focussed on nutrition,
      targeted at women.

PMID- 20047935
TI  - Fetal environment and early age at natural menopause in a British birth cohort
      study.
AB  - BACKGROUND: Early life development may influence the timing of natural menopause
      through association with size of the initial follicle pool or early follicular
      loss. This study examines the relationships of birthweight, gestational age and
      birthweight standardized by gestational age with early menopause in the 1958
      British birth cohort study. METHODS: Study participants were over 2900 women with
      data on birthweight, gestational age (obtained at birth), menopausal status at
      age 44-45 years and potential confounding factors. Logistic regression was used
      to study relationships of birthweight, gestational age and birthweight
      standardized by gestational age with post-menopausal status by 44-45 years, with
      and without adjustments for confounding factors. RESULTS: There was a U-shaped
      association between birthweight and menopausal status at 44-45 years: women at
      either extremes of birthweight (<2.5 and >or=4.0 kg) had increased odds of post
      menopausal status compared with those weighing 3.0-3.49 kg [odds ratio (OR) =
      1.91, 95% confidence interval (CI) 1.08, 3.38; 1.81, 95% CI 1.11, 2.97,
      respectively]. Women with higher birthweight standardized by gestational age
      (which indicates faster fetal growth rate) also had increased odds of being post
      menopausal by 44-45 years (OR for fastest quarter versus second fastest quarter =
      1.80; 95% CI 1.16, 2.81). These associations persisted after adjustment for
      socioeconomic position at birth, adult smoking status and use of oral
      contraceptives. CONCLUSIONS: These findings suggest that variations in fetal
      environment may be associated with the timing of menopause. Given that extremes
      of birthweight and higher birthweight standardized by gestational age were
      associated with earlier age at menopause, mechanisms related to these
      characteristics that also regulate ovarian function should be investigated
      further.

PMID- 20047937
TI  - Multi-scale biothermal and biomechanical behaviours of biological materials.

PMID- 20047936
TI  - Dynamic microfunnel culture enhances mouse embryo development and pregnancy
      rates.
AB  - BACKGROUND: Despite advances in in vitro manipulation of preimplantation embryos,
      there is still a reduction in the quality of embryos produced leading to lower
      pregnancy rates compared with embryos produced in vivo. We hypothesized that a
      dynamic microfunnel embryo culture system would enhance outcomes by better
      mimicking the fluid-mechanical and biochemical stimulation embryos experience in
      vivo from ciliary currents and oviductal contractions. METHODS AND RESULTS: Mouse
      embryos were cultured in microdrop-static control, microfunnel-static control or
      microfunnel-dynamic conditions with microfluidics. All groups tested had greater
      than 90% total blastocyst development from zygotes after 96 h culture. Blastocyst
      developmental stage was significantly enhanced (P < 0.01) under dynamic
      microfunnel culture conditions as evidenced by an increased percentage of
      hatching or hatched blastocysts (Microdrop-control 31%; Microfunnel-control 23%;
      Microfunnel-pulsatile 71%) and significantly higher (P < 0.01) average number of
      cells per blastocyst (Microdrop-control 67 +/- 3; Microfunnel-control 60 +/- 3;
      Microfunnel-pulsatile 109 +/- 5). Blastocyst cell numbers in dynamic microfunnel
      cultures (109 +/- 5) more closely matched numbers obtained from in vivo grown
      blastocysts (144 +/- 9). Importantly, dynamic microfunnel culture significantly
      improved embryo implantation and ongoing pregnancy rates over static culture to
      levels approaching that of in utero derived preimplantation embryos. CONCLUSIONS:
      The improved pregnancy outcomes along with the simple and user-friendly design of
      the microfluidic/microfunnel system has potential to alleviate many
      inefficiencies in embryo production for biomedical research, genetic gain in
      domestic species and assisted reproductive technologies in humans.

PMID- 20047938
TI  - A multi-scale view of skin thermal pain: from nociception to pain sensation.
AB  - All biological bodies live in a thermal environment, including the human body,
      where skin is the interface with a protecting function. When the temperature is
      out of the normal physiological range, skin fails to protect, and the pain
      sensation is evoked. Furthermore, in medicine, with advances in laser, microwave
      and similar technologies, various thermal therapeutic methods have been widely
      used to cure disease/injury involving skin tissue. However, the corresponding
      problem of pain relief has limited further application and development of these
      thermal treatments. Skin thermal pain is induced through both direct (i.e. an
      increase/decrease in temperature) and indirect (e.g. thermomechanical and
      thermochemical) ways, and is governed by complicated thermomechanical-chemical
      neurophysiological responses. However, a complete understanding of the underlying
      mechanisms is still far from clear. In this article, starting from an engineering
      perspective, we aim to recast the biological behaviour of skin in engineering
      system parlance. Then, by coupling the concepts of engineering with established
      methods in neuroscience, we attempt to establish multi-scale modelling of skin
      thermal pain through ion channel to pain sensation. The model takes into account
      skin morphological plausibility, the thermomechanical response of skin tissue and
      the biophysical and neurological mechanisms of pain sensation.

PMID- 20047939
TI  - Multi-scale heat and mass transfer modelling of cell and tissue cryopreservation.
AB  - Cells and tissues undergo complex physical processes during cryopreservation.
      Understanding the underlying physical phenomena is critical to improve current
      cryopreservation methods and to develop new techniques. Here, we describe multi
      scale approaches for modelling cell and tissue cryopreservation including heat
      transfer at macroscale level, crystallization, cell volume change and mass
      transport across cell membranes at microscale level. These multi-scale approaches
      allow us to study cell and tissue cryopreservation.

PMID- 20047940
TI  - Fixed negative charge and the Donnan effect: a description of the driving forces
      associated with brain tissue swelling and oedema.
AB  - Cerebral oedema or brain tissue swelling is a significant complication following
      traumatic brain injury or stroke that can increase the intracranial pressure
      (ICP) and impair blood flow. Here, we have identified a potential driver of
      oedema: the negatively charged molecules fixed within cells. This fixed charge
      density (FCD), once exposed, could increase ICP through the Donnan effect. We
      have shown that metabolic processes and membrane integrity are required for
      concealing this FCD as slices of rat cortex swelled immediately (within 30 min)
      following dissection if treated with 2 deoxyglucose + cyanide (2DG+CN) or Triton
      X-100. Slices given ample oxygen and glucose, however, did not swell
      significantly. We also found that dead brain tissue swells and shrinks in
      response to changes in ionic strength of the bathing medium, which suggests that
      the Donnan effect is capable of pressurizing and swelling brain tissue. As
      predicted, a non-ionic osmolyte, 1,2 propanediol, elicited no volume change at
      2000 x 10(-3) osmoles l(-1) (Osm). Swelling data were well described by triphasic
      mixture theory with the calculated reference state FCD similar to that measured
      with a 1,9 dimethylmethylene blue assay. Taken together, these data suggest that
      intracellular fixed charges may contribute to the driving forces responsible for
      brain swelling.

PMID- 20047941
TI  - Novel early response genes in osteoblasts exposed to dynamic fluid flow.
AB  - Cyclic mechanical loads applied to the skeleton from habitual physical activity
      result in increased bone formation. These loads lead to dynamic pressure
      gradients and oscillatory flow of bone interstitial fluid, which, in turn,
      exposes cells resident in the bony matrix to oscillatory fluid shear stress.
      Dynamic fluid flow has previously been shown to be a potent anabolic stimulus for
      cultured osteoblasts. In this study, we used cDNA microarrays to examine early
      phase, broad-spectrum gene expression in MC3T3-E1 osteoblasts in response to
      physical stimulation. RNA was harvested at 30 min and 1 h post-stimulation. RNA
      was used for microarray hybridization as well as subsequent reverse transcription
      polymerase chain reaction (RT-PCR) validation of expression levels for selected
      genes. Microarray results were analysed by both functional and expression profile
      clustering. We identified a small number of genes at both the 30 min and 1 h
      timepoints that were either upregulated or downregulated with flow compared to no
      flow control by twofold or more. From the group of genes upregulated at 30 min,
      we selected nine for RT-PCR confirmation. All were found to be upregulated by at
      least twofold. We identify a novel set of early response genes potentially
      involved in mediating the anabolic response of MC3T3 osteoblasts to flow, and
      provide functional groupings of these genes that may shed light on the relevant
      mechanosensory pathways involved.

PMID- 20047942
TI  - Intercellular calcium wave propagation in linear and circuit-like bone cell
      networks.
AB  - In the present study, the mechanism of intercellular calcium wave propagation in
      bone cell networks was identified. By using micro-contact printing and self
      assembled monolayer technologies, two types of in vitro bone cell networks were
      constructed: open-ended linear chains and looped hexagonal networks with
      precisely controlled intercellular distances. Intracellular calcium responses of
      the cells were recorded and analysed when a single cell in the network was
      mechanically stimulated by nano-indentation. The looped cell network was shown to
      be more efficient than the linear pattern in transferring calcium signals from
      cell to cell. This phenomenon was further examined by pathway-inhibition studies.
      Intercellular calcium wave propagation was significantly impeded when
      extracellular adenosine triphosphate (ATP) in the medium was hydrolysed. Chemical
      uncoupling of gap junctions, however, did not significantly decrease the
      transferred distance of the calcium wave in the cell networks. Thus, it is
      extracellular ATP diffusion, rather than molecular transport through gap
      junctions, that dominantly mediates the transmission of mechanically elicited
      intercellular calcium waves in bone cells. The inhibition studies also
      demonstrated that the mechanical stimulation-induced calcium responses required
      extracellular calcium influx, whereas the ATP-elicited calcium wave relied on
      calcium release from the calcium store of the endoplasmic reticulum.

PMID- 20047943
TI  - Whole cell mechanics of contractile fibroblasts: relations between effective
      cellular and extracellular matrix moduli.
AB  - While much is known about the subcellular structures responsible for the
      mechanical functioning of a contractile fibroblast, debate exists about how these
      components combine to endow a cell with its form and mechanical function. We
      present an analysis of mechanical characterization experiments performed on bio
      artificial tissue constructs, which we believe serve as a more realistic testing
      environment than two-dimensional cell culture. These model tissues capture many
      features of real tissues with the advantage that they can be engineered to model
      different physiological and pathological characteristics. We study here a model
      tissue consisting of reconstituted type I collagen and varying concentrations of
      activated contractile fibroblasts that is relevant to modelling different stages
      of wound healing. We applied this system to assess how cell and extracellular
      matrix (ECM) mechanics vary with cell concentration. Short-term and long-term
      moduli of the ECM were estimated through analytical and numerical analysis of two
      phase elastic solids containing cell-shaped voids. The relative properties of
      cells were then deduced from the results of numerical analyses of two-phase
      elastic solids containing mechanically isotropic cells of varying modulus. With
      increasing cell concentration, the short-term and long-term tangent moduli of the
      reconstituted collagen ECM increased sharply from a baseline value, while those
      of the cells decreased monotonically.

PMID- 20047944
TI  - Prediction and parametric analysis of thermal profiles within heated human skin
      using the boundary element method.
AB  - In this paper, an axisymmetric model of the human skin is developed to simulate
      the steady-state temperature distribution during contact with a hot solid.
      Simulations are carried out using the boundary element method. This study seeks
      to investigate the feasibility of using the boundary element method in the
      studies of burn. A sensitivity analysis is carried out to examine the effects of
      various parameters on the temperature distribution inside the skin during burn.
      Furthermore, a statistical analysis based on the Taguchi method is performed to
      determine the combination of factors that produce the desired outcome (least
      increase in temperature). In order to validate the accuracy of the numerical
      scheme, results obtained using the boundary element method are compared with the
      solutions obtained using the more established finite-element method.

PMID- 20047945
TI  - Strain rate sensitivity of skin tissue under thermomechanical loading.
AB  - There have been limited studies addressing the thermally dependent mechanical
      properties of skin tissue, although this can contribute to a variety of medical
      applications. To address this, an experimental study on the tensile behaviour of
      pig skin tissue under different thermal loading conditions and different
      mechanical stretching rates was performed. The results indicate that there is a
      significant variation among skin tensile behaviours under different temperatures
      and loading rates, which is correlated with dermal collagen denaturation. The
      Ogden model was used to summarize the effect of the strain rate and the
      temperature upon the measured constitutive response through two parameters (alpha
      and mu). These results can be used in future models to improve clinical thermal
      treatments for skin tissue.

PMID- 20047946
TI  - Complete genomic structure of the cultivated rice endophyte Azospirillum sp.
      B510.
AB  - We determined the nucleotide sequence of the entire genome of a diazotrophic
      endophyte, Azospirillum sp. B510. Strain B510 is an endophytic bacterium isolated
      from stems of rice plants (Oryza sativa cv. Nipponbare). The genome of B510
      consisted of a single chromosome (3,311,395 bp) and six plasmids, designated as
      pAB510a (1,455,109 bp), pAB510b (723,779 bp), pAB510c (681,723 bp), pAB510d
      (628,837 bp), pAB510e (537,299 bp), and pAB510f (261,596 bp). The chromosome
      bears 2893 potential protein-encoding genes, two sets of rRNA gene clusters
      (rrns), and 45 tRNA genes representing 37 tRNA species. The genomes of the six
      plasmids contained a total of 3416 protein-encoding genes, seven sets of rrns,
      and 34 tRNAs representing 19 tRNA species. Eight genes for plasmid-specific tRNA
      species are located on either pAB510a or pAB510d. Two out of eight genomic
      islands are inserted in the plasmids, pAB510b and pAB510e, and one of the islands
      is inserted into trnfM-CAU in the rrn located on pAB510e. Genes other than the
      nif gene cluster that are involved in N(2) fixation and are homologues of
      Bradyrhizobium japonicum USDA110 include fixABCX, fixNOQP, fixHIS, fixG, and
      fixLJK. Three putative plant hormone-related genes encoding tryptophan 2
      monooxytenase (iaaM) and indole-3-acetaldehyde hydrolase (iaaH), which are
      involved in IAA biosynthesis, and ACC deaminase (acdS), which reduces ethylene
      levels, were identified. Multiple gene-clusters for tripartite ATP-independent
      periplasmic-transport systems and a diverse set of malic enzymes were identified,
      suggesting that B510 utilizes C(4)-dicarboxylate during its symbiotic
      relationship with the host plant.

PMID- 20047947
TI  - Determination of the in vivo structural DNA loop organization in the genomic
      region of the rat albumin locus by means of a topological approach.
AB  - Nuclear DNA of metazoans is organized in supercoiled loops anchored to a
      proteinaceous substructure known as the nuclear matrix (NM). DNA is anchored to
      the NM by non-coding sequences known as matrix attachment regions (MARs). There
      are no consensus sequences for identification of MARs and not all potential MARs
      are actually bound to the NM constituting loop attachment regions (LARs).
      Fundamental processes of nuclear physiology occur at macromolecular complexes
      organized on the NM; thus, the topological organization of DNA loops must be
      important. Here, we describe a general method for determining the structural DNA
      loop organization in any large genomic region with a known sequence. The method
      exploits the topological properties of loop DNA attached to the NM and elementary
      topological principles such as that points in a deformable string (DNA) can be
      positionally mapped relative to a position-reference invariant (NM), and from
      such mapping, the configuration of the string in third dimension can be deduced.
      Therefore, it is possible to determine the specific DNA loop configuration
      without previous characterization of the LARs involved. We determined in
      hepatocytes and B-lymphocytes of the rat the DNA loop organization of a genomic
      region that contains four members of the albumin gene family.

PMID- 20047948
TI  - Neuronopathic Gaucher disease in the mouse: viable combined selective saposin C
      deficiency and mutant glucocerebrosidase (V394L) mice with glucosylsphingosine
      and glucosylceramide accumulation and progressive neurological deficits.
AB  - Gaucher disease is caused by defective acid beta-glucosidase (GCase) function.
      Saposin C is a lysosomal protein needed for optimal GCase activity. To test the
      in vivo effects of saposin C on GCase, saposin C deficient mice (C-/-) were
      backcrossed to point mutated GCase (V394L/V394L) mice. The resultant mice (4L;C*)
      began to exhibit CNS abnormalities approximately 30 days: first as hindlimb
      paresis, then progressive tremor and ataxia. Death occurred approximately 48 days
      due to neurological deficits. Axonal degeneration was evident in brain stem,
      spinal cord and white matter of cerebellum accompanied by increasing infiltration
      of the brain stem, cortex and thalamus by CD68 positive microglial cells and
      activation of astrocytes. Electron microscopy showed inclusion bodies in neuronal
      processes and degenerating cells. Accumulation of p62 and Lamp2 were prominent in
      the brain suggesting the impairment of autophagosome/lysosome function. This
      phenotype was different from either V394L/V394L or C-/- alone. Relative to
      V394L/V394L mice, 4L;C* mice had diminished GCase protein and activity. Marked
      increases (20- to 30-fold) of glucosylsphingosine (GS) and moderate elevation
      (1.5- to 3-fold) of glucosylceramide (GC) were in 4L;C* brains. Visceral tissues
      had increases of GS and GC, but no storage cells were found. Neuronal cells in
      thick hippocampal slices from 4L;C* mice had significantly attenuated long-term
      potentiation, presumably resulting from substrate accumulation. The 4L;C* mouse
      mimics the CNS phenotype and biochemistry of some type 3 (neuronopathic) variants
      of Gaucher disease and is a unique model suitable for testing pharmacological
      chaperone and substrate reduction therapies, and investigating the mechanisms of
      neuronopathic Gaucher disease.

PMID- 20047949
TI  - CTCF binding is not the epigenetic mark that establishes post-fertilization
      methylation imprinting in the transgenic H19 ICR.
AB  - Imprinted expression of the mouse Igf2/H19 locus is controlled by parent-of
      origin-specific methylation of the imprinting control region (ICR). We previously
      demonstrated that when placed in a heterologous genomic context, the H19 ICR
      fragment contains an intrinsic activity that allows it to acquire differential
      methylation in somatic cells but not in germ cells. In the present study, we
      investigated the requirements for the CTCF-binding sites of the ICR in the
      acquisition of post-fertilization methylation. To this end, two mutant ICR
      fragments were introduced into the human beta-globin locus in a yeast artificial
      chromosome transgenic mouse (TgM) model: 4xMut had mutations in all four ICR CTCF
      binding sites that prevented CTCF binding but retained the methylation target CpG
      motifs, and -9CG harbored mutations in the CpG motifs within the CTCF-binding
      sites but each site retained constitutive CTCF-binding activity. In TgM germ
      cells and pre-implantation blastocysts, the absence of CTCF-binding sites (4xMut)
      did not lead to hypermethylation of the transgenic H19 ICR. However, after
      implantation, the mutations of CTCF sites (4xMut and -9CG) affected the
      maintenance of methylation. These results demonstrated that although the CTCF
      binding sites are indispensable for maintenance of the unmethylated state of the
      maternal ICR in post-implantation embryos, they are not required to establish
      paternal-allele-specific methylation of the transgenic H19 ICR in pre
      implantation embryos.

PMID- 20047951
TI  - Multiplex SILAC analysis of a cellular TDP-43 proteinopathy model reveals protein
      inclusions associated with SUMOylation and diverse polyubiquitin chains.
AB  - Transactive response (TAR) DNA-binding protein 43 (TDP-43) is a major protein
      component within ubiquitin-positive inclusions of frontotemporal lobar
      degeneration and amyotrophic lateral sclerosis. Although TDP-43 is a nuclear
      DNA/RNA-binding protein, in pathological conditions, TDP-43 has been reported to
      redistribute to the cytoplasm where it is cleaved and forms insoluble,
      ubiquitinated, and phosphorylated inclusions. Here we present a cellular model in
      which full-length human TDP-43 or a splicing isoform (TDP-S6) that lacks the C
      terminus is overexpressed in a human cell line and mouse primary neurons. Whereas
      recombinant and endogenous TDP-43 was primarily localized in the nucleus, the
      shorter TDP-S6 formed highly insoluble cytoplasmic and nuclear inclusions
      reminiscent of disease-specific pathology. Western blot analysis of detergent
      insoluble extracts showed an increase in high molecular weight immunoreactive
      species for TDP-S6 compared with TDP-43, consistent with ubiquitination or
      ubiquitin-like modifications. We used a multiplex stable isotope labeling with
      amino acids in cell culture approach to compare the detergent-insoluble proteome
      from mock-, TDP-43-, and TDP-S6-transfected cells. TDP-S6 overexpression caused a
      concomitant increase in both ubiquitin (Ub) and the small Ub-like modifier-2/3
      (SUMO-2/3) within the insoluble proteome. Similarly, full-length TDP-43
      overexpression also resulted in the elevation of SUMO-2/3. Immunofluorescence
      showed strong co-localization of endogenous Ub with both cytoplasmic and nuclear
      TDP-S6 inclusions, whereas SUMO-2/3 was co-localized mainly with the nuclear
      inclusions. Quantitative mass spectrometry further revealed that mixed Lys-48 and
      Lys-63 polyUb linkages were associated with the TDP insoluble fractions. Together
      our data indicate that expression of a TDP-43 splice variant lacking a C terminus
      recapitulates many of the cellular and biochemical features associated with
      disease pathology and that the interplay of ubiquitination and SUMOylation may
      have an important role in TDP-43 regulation.

PMID- 20047950
TI  - Simultaneous characterization of glyco- and phosphoproteomes of mouse brain
      membrane proteome with electrostatic repulsion hydrophilic interaction
      chromatography.
AB  - Characterization of glyco- and phosphoproteins as well as their modification
      sites poses many challenges, the greatest being loss of their signals during mass
      spectrometric detection due to substoichiometric amounts and the ion suppression
      effect caused by peptides of high abundance. We report here an optimized protocol
      using electrostatic repulsion hydrophilic interaction chromatography for the
      simultaneous enrichment of glyco- and phosphopeptides from mouse brain membrane
      protein digest. With this protocol, we successfully identified 544 unique
      glycoproteins and 922 glycosylation sites, which were significantly higher than
      those from the commonly used hydrazide chemistry method (192 glycoproteins and
      345 glycosylation sites). Moreover, a total of 383 phosphoproteins and 915
      phosphorylation sites were recovered from the sample, suggesting that this
      protocol has the potential to enrich both glycopeptides and phosphopeptides
      simultaneously. Of the total 995 glycosylation sites identified from both
      methods, 96% were considered new as they were either annotated as putative or not
      documented in the newly released Swiss-Prot database. Thus, this study could be
      of significant value in complementing the current glycoprotein database and
      provides a unique opportunity to study the complex interaction of two different
      post-translational modifications in health and disease without being affected by
      interexperimental variations.

PMID- 20047952
TI  - Options for fertility preservation in prepubertal boys.
AB  - BACKGROUND: Fertility in adult life may be severely impaired by gonadotoxic
      therapies. For young boys who do not yet produce spermatozoa, cryopreservation of
      immature testicular tissue (ITT) is an option to preserve their fertility, albeit
      still experimental. This paper covers current options for ITT cryopreservation
      and fertility restoration. METHODS: Relevant studies were identified by an
      extensive Medline search of English and French language articles. Search terms
      were: gonadotoxicity, cytoprotection, cryopreservation, ITT, spermatogonia,
      testicular transplantation, testicular grafting and in vitro maturation (IVM).
      RESULTS: Although no effective gonadoprotective drug is yet available for in vivo
      spermatogonial stem cell protection in humans, current evidence supports the
      feasibility of ITT cryopreservation before gonadotoxic treatment with a view to
      fertility preservation. Controlled slow freezing with dimethyl sulfoxide allows
      survival and proliferation of human spermatogonia after xenotransplantation, but
      only partial differentiation. Animal data look promising, since healthy offspring
      have been obtained after transplantation of frozen testicular cell suspensions or
      tissue pieces. However, none of the fertility restoration options from frozen
      tissue, i.e. cell suspension transplantation, tissue grafting and IVM have proved
      efficient and safe in humans as yet. CONCLUSION: While additional evidence is
      required to define optimal conditions for ITT cryopreservation with a view to
      transplantation or IVM, the putative indications for such techniques, as well as
      their limitations according to disease, are outlined.

PMID- 20047953
TI  - Targets of Raf in tumorigenesis.
AB  - Some 25 years ago, Raf was discovered as the transforming principle shared by a
      murine sarcoma and an avian carcinoma virus. Thus, Raf and tumorigenesis have
      been connected from the very beginning. Ten years later, the work of many groups
      instated Raf as the link between Ras, the oncogene most frequently mutated in
      human cancers, and the mitogen-activated protein kinase/extracellular signal
      regulated kinase kinase (MEK/ERK) module, which with its manifold substrates can
      contribute to different aspects of carcinogenesis. Finally, the discovery of
      activating B-Raf mutations in a subset of human cancers, notably melanomas,
      conclusively established Raf as a major player in tumor development. Recent
      studies in animal models now show that endogenous C-Raf is essential for the
      development and maintenance of Ras-induced epidermal tumors. Surprisingly, the
      role of C-Raf in this case is not that of an mitogen-activated protein kinase
      activator, but rather that of an endogenous inhibitor of Rho signaling, expanding
      the range of tumor-related Raf targets. This review focuses on old and new
      targets of Raf in tumorigenesis.

PMID- 20047954
TI  - Variants in blood pressure genes and the risk of renal cell carcinoma.
AB  - Hypertension is a known risk factor for renal cell carcinoma (RCC), although the
      underlying biological mechanisms of its action are unknown. To clarify the role
      of hypertension in RCC, we examined the risk of RCC in relation to 142 single
      nucleotide polymorphisms (SNPs) in eight genes having a role in blood pressure
      control. We analyzed 777 incident and histologically confirmed RCC cases and 1035
      controls who completed an in-person interview as part of a multi-center, hospital
      based case-control study in Central Europe. Genotyping was conducted with an
      Illumina GoldenGate Oligo Pool All assay using germ line DNA. Of the eight genes
      examined, AGT (angiotensinogen) was most strongly associated with RCC (minimum P
      value permutation test = 0.02). Of the 17 AGT tagging SNPs considered,
      associations were strongest for rs1326889 [odds ratio (OR) = 1.35, 95% confidence
      interval (CI) = 1.15-1.58] and rs2493137 (OR = 1.31, 95% CI = 1.12-1.54), which
      are located in the promoter. Stratified analysis revealed that the effects of the
      AGT SNPs were statistically significant in participants with hypertension or high
      body mass index (BMI) (> or =25 kg/m(2)), but not in subjects without
      hypertension and with a normal BMI (<25 kg/m(2)). Also, haplotypes with risk
      conferring alleles of markers located in the promoter and intron 1 regions of AGT
      were significantly associated with RCC compared with the common haplotype in
      subjects with hypertension or high BMI (global P = 0.003). Our findings suggest
      that common genetic variants of AGT, particularly those in the promoter, increase
      RCC risk among subjects who are hypertensive or overweight.

PMID- 20047955
TI  - Lineage-specific patterns of functional diversification in the alpha- and beta
      globin gene families of tetrapod vertebrates.
AB  - The alpha- and beta-globin gene families of jawed vertebrates have diversified
      with respect to both gene function and the developmental timing of gene
      expression. Phylogenetic reconstructions of globin gene family evolution have
      provided suggestive evidence that the developmental regulation of hemoglobin
      synthesis has evolved independently in multiple vertebrate lineages. For example,
      the embryonic beta-like globin genes of birds and placental mammals are not 1:1
      orthologs. Despite the similarity in developmental expression profiles, the genes
      are independently derived from lineage-specific duplications of a beta-globin pro
      ortholog. This suggests the possibility that other vertebrate taxa may also
      possess distinct repertoires of globin genes that were produced by repeated
      rounds of lineage-specific gene duplication and divergence. Until recently,
      investigations into this possibility have been hindered by the dearth of genomic
      sequence data from nonmammalian vertebrates. Here, we report new insights into
      globin gene family evolution that were provided by a phylogenetic analysis of
      vertebrate globins combined with a comparative genomic analysis of three key
      sauropsid taxa: a squamate reptile (anole lizard, Anolis carolinensis), a
      passeriform bird (zebra finch, Taeniopygia guttata), and a galliform bird
      (chicken, Gallus gallus). The main objectives of this study were 1) to
      characterize evolutionary changes in the size and membership composition of the
      alpha- and beta-globin gene families of tetrapod vertebrates and 2) to test
      whether functional diversification of the globin gene clusters occurred
      independently in different tetrapod lineages. Results of our comparative genomic
      analysis revealed several intriguing patterns of gene turnover in the globin gene
      clusters of different taxa. Lineage-specific differences in gene content were
      especially pronounced in the beta-globin gene family, as phylogenetic
      reconstructions revealed that amphibians, lepidosaurs (as represented by anole
      lizard), archosaurs (as represented by zebra finch and chicken), and mammals each
      possess a distinct independently derived repertoire of beta-like globin genes. In
      contrast to the ancient functional diversification of the alpha-globin gene
      cluster in the stem lineage of tetrapods, the physiological division of labor
      between early- and late-expressed genes in the beta-globin gene cluster appears
      to have evolved independently in several tetrapod lineages.

PMID- 20047956
TI  - Insight into the induction mechanism of the GntR/HutC bacterial transcription
      regulator YvoA.
AB  - YvoA is a GntR/HutC transcription regulator from Bacillus subtilis implicated in
      the regulation of genes from the N-acetylglucosamine-degrading pathway. Its 2.4-A
      crystal structure reveals a homodimeric assembly with each monomer displaying a
      two-domain fold. The C-terminal domain, which binds the effector N
      acetylglucosamine-6-phosphate, adopts a chorismate lyase fold, whereas the N
      terminal domain contains a winged helix-turn-helix DNA-binding domain. Isothermal
      titration calorimetry and site-directed mutagenesis revealed that the effector
      binding site in YvoA coincides with the active site of related chorismate lyase
      from Escherichia coli. The characterization of the DNA- and effector-binding
      properties of two disulfide-bridged mutants that lock YvoA in two distinct
      conformational states provides for the first time detailed insight into the
      allosteric mechanism through which effector binding modulates DNA binding and,
      thereby regulates transcription in a representative GntR/HutC family member.
      Central to this allosteric coupling mechanism is a loop-to-helix transition with
      the dipole of the newly formed helix pointing toward the phosphate of the
      effector. This transition goes in hand with the emergence of internal symmetry in
      the effector-binding domain and, in addition, leads to a 122 degrees rotation of
      the DNA-binding domains that is best described as a jumping-jack-like motion.

PMID- 20047957
TI  - Tfold: efficient in silico prediction of non-coding RNA secondary structures.
AB  - Predicting RNA secondary structures is a very important task, and continues to be
      a challenging problem, even though several methods and algorithms are proposed in
      the literature. In this article, we propose an algorithm called Tfold, for
      predicting non-coding RNA secondary structures. Tfold takes as input a RNA
      sequence for which the secondary structure is searched and a set of aligned
      homologous sequences. It combines criteria of stability, conservation and
      covariation in order to search for stems and pseudoknots (whatever their type).
      Stems are searched recursively, from the most to the least stable. Tfold uses an
      algorithm called SSCA for selecting the most appropriate sequences from a large
      set of homologous sequences (taken from a database for example) to use for the
      prediction. Tfold can take into account one or several stems considered by the
      user as belonging to the secondary structure. Tfold can return several structures
      (if requested by the user) when 'rival' stems are found. Tfold has a complexity
      of O(n(2)), with n the sequence length. The developed software, which offers
      several different uses, is available on the web site: http://tfold.ibisc.univ
      evry.fr/TFold.

PMID- 20047958
TI  - Quality measures for protein alignment benchmarks.
AB  - Multiple protein sequence alignment methods are central to many applications in
      molecular biology. These methods are typically assessed on benchmark datasets
      including BALIBASE, OXBENCH, PREFAB and SABMARK, which are important to
      biologists in making informed choices between programs. In this article,
      annotations of domain homology and secondary structure are used to define new
      measures of alignment quality and are used to make the first systematic,
      independent evaluation of these benchmarks. These measures indicate sensitivity
      and specificity while avoiding the ambiguous residue correspondences and
      arbitrary distance cutoffs inherent to structural superpositions. Alignments by
      selected methods that indicate high-confidence columns (ALIGN-M, DIALIGN-T, FSA
      and MUSCLE) are also assessed. Fold space coverage and effective benchmark
      database sizes are estimated by reference to domain annotations, and significant
      redundancy is found in all benchmarks except SABMARK. Questionable alignments are
      found in all benchmarks, especially in BALIBASE where 87% of sequences have
      unknown structure, 20% of columns contain different folds according to
      SUPERFAMILY and 30% of 'core block' columns have conflicting secondary structure
      according to DSSP. A careful analysis of current protein multiple alignment
      benchmarks calls into question their ability to determine reliable algorithm
      rankings.

PMID- 20047959
TI  - Electrostatic hot spot on DNA-binding domains mediates phosphate desolvation and
      the pre-organization of specificity determinant side chains.
AB  - A major obstacle towards elucidating the molecular basis of transcriptional
      regulation is the lack of a detailed understanding of the interplay between non
      specific and specific protein-DNA interactions. Based on molecular dynamics
      simulations of C(2)H(2) zinc fingers (ZFs) and engrailed homeodomain
      transcription factors (TFs), we show that each of the studied DNA-binding domains
      has a set of highly constrained side chains in preset configurations ready to
      form hydrogen bonds with the DNA backbone. Interestingly, those domains that bury
      their recognition helix into the major groove are found to have an electrostatic
      hot spot for Cl(-) ions located on the same binding cavity as the most buried DNA
      phosphate. The spot is characterized by three protein hydrogen bond donors, often
      including two basic side chains. If bound, Cl(-) ions, likely mimicking
      phosphates, steer side chains that end up forming specific contacts with bases
      into bound-like conformations. These findings are consistent with a multi-step
      DNA-binding mechanism in which a pre-organized set of TF side chains assist in
      the desolvation of phosphates into well defined sites, prompting the re
      organization of specificity determining side chains into conformations suitable
      for the recognition of their cognate sequence.

PMID- 20047960
TI  - Investigating the role of the Est3 protein in yeast telomere replication.
AB  - The Est3 subunit of yeast telomerase, which adopts a predicted OB-fold, is
      essential for telomere replication. To assess the possible contributions that
      Est3 might make to enzyme catalysis, we compared telomerase activity from wild
      type and est3-Delta strains of Saccharomyces castellii, which revealed that loss
      of the Est3 subunit results in a 2- to 3-fold decline in nucleotide addition.
      This effect was not primer-specific, based on assessment of a panel of primers
      that spanned the template of the S. castellii telomerase RNA. Furthermore, using
      nuclear magnetic resonance chemical shift perturbation, no chemical shift change
      was observed at any site in the protein upon addition of single-stranded DNA,
      arguing against a role for Est3 in recognition of telomeric substrates by
      telomerase. Addition of exogenous Est3 protein, including mutant Est3 proteins
      that are severely impaired for telomere replication in vivo, fully restored
      activity in est3-Delta telomerase reactions. Thus, Est3 performs an in vivo
      regulatory function in telomere replication, which is distinct from any potential
      contribution that Est3 might make to telomerase activity.

PMID- 20047961
TI  - Finding regulatory DNA motifs using alignment-free evolutionary conservation
      information.
AB  - As an increasing number of eukaryotic genomes are being sequenced, comparative
      studies aimed at detecting regulatory elements in intergenic sequences are
      becoming more prevalent. Most comparative methods for transcription factor (TF)
      binding site discovery make use of global or local alignments of orthologous
      regulatory regions to assess whether a particular DNA site is conserved across
      related organisms, and thus more likely to be functional. Since binding sites are
      usually short, sometimes degenerate, and often independent of orientation,
      alignment algorithms may not align them correctly. Here, we present a novel,
      alignment-free approach for using conservation information for TF binding site
      discovery. We relax the definition of conserved sites: we consider a DNA site
      within a regulatory region to be conserved in an orthologous sequence if it
      occurs anywhere in that sequence, irrespective of orientation. We use this
      definition to derive informative priors over DNA sequence positions, and
      incorporate these priors into a Gibbs sampling algorithm for motif discovery. Our
      approach is simple and fast. It requires neither sequence alignments nor the
      phylogenetic relationships between the orthologous sequences, yet it is more
      effective on real biological data than methods that do.

PMID- 20047962
TI  - Protein arginine methyltransferase 6 regulates multiple aspects of gene
      expression.
AB  - It is well established that transcription and alternative splicing events are
      functionally coupled during gene expression. Here, we report that protein
      arginine N-methyltransferase 6 (PRMT6) may play a key role in this coupling
      process by functioning as a transcriptional coactivator that can also regulate
      alternative splicing. PRMT6 coactivates the progesterone, glucocorticoid and
      oestrogen receptors in luciferase reporter assays in a hormone-dependent manner.
      In addition, small interfering RNA (siRNA) oligonucleotide duplex knockdown of
      PRMT6 disrupts oestrogen-stimulated transcription of endogenous GREB1 and
      progesterone receptor in MCF-7 breast cancer cells, demonstrating the importance
      of PRMT6 in hormone-dependent transcription. In contrast, the regulation of
      alternative splicing by PRMT6 is hormone independent. siRNA knockdown of PRMT6
      increases the exon inclusion:skipping ratio of alternatively spliced exons in
      endogenous vascular endothelial growth factor and spleen tyrosine kinase RNA
      transcripts in both the presence and absence of oestrogen. These results
      demonstrate that PRMT6 has a dual role in regulating gene expression and that
      these two functions can occur independently of each other.

PMID- 20047963
TI  - Differential coregulator requirements for function of the hematopoietic
      transcription factor GATA-1 at endogenous loci.
AB  - The critical regulator of hematopoiesis GATA-1 recruits diverse coregulators to
      chromatin, which mediate transcriptional activation and repression. These
      coregulators include the cell-type-specific multi-zinc finger protein Friend of
      GATA-1 (FOG-1), the histone acetyltransferase CREB binding protein (CBP), and the
      key component of the Mediator complex Med1. While FOG-1 is an established GATA-1
      coregulator, the importance of interactions between GATA-1 and other coregulators
      is poorly understood. Furthermore, whether GATA-1 utilizes multiple coregulators
      at all loci, or if certain coregulators are dedicated to specific loci is
      unknown. We compared the capacity of GATA-1 to recruit and utilize FOG-1 and Med1
      at activated and repressed target genes. Similar to FOG-1, GATA-1 recruited Med1
      to activated genes, and the kinetics of FOG-1 and Med1 recruitment were similar.
      GATA-1 recruited Med1 in Fog1(-/-) cells, indicating that GATA-1-mediated Med1
      recruitment is FOG-1-independent. In contrast to FOG-1, GATA-1 evicted Med1
      during transcriptional repression. Whereas knocking-down FOG-1 had catastrophic
      effects on GATA-1-mediated activation and repression, knocking-down Med1 modestly
      impaired GATA-1 activity only at select loci. These results illustrate both
      similarities and differences between GATA-1-mediated recruitment of FOG-1 and
      Med1 to chromatin, with a fundamental difference being the quantitatively greater
      requirement for FOG-1.

PMID- 20047964
TI  - A novel mechanism for the scission of double-stranded DNA: BfiI cuts both 3'-5'
      and 5'-3' strands by rotating a single active site.
AB  - Metal-dependent nucleases that generate double-strand breaks in DNA often possess
      two symmetrically-equivalent subunits, arranged so that the active sites from
      each subunit act on opposite DNA strands. Restriction endonuclease BfiI belongs
      to the phospholipase D (PLD) superfamily and does not require metal ions for DNA
      cleavage. It exists as a dimer but has at its subunit interface a single active
      site that acts sequentially on both DNA strands. The active site contains two
      identical histidines related by 2-fold symmetry, one from each subunit. This
      symmetrical arrangement raises two questions: first, what is the role and the
      contribution to catalysis of each His residue; secondly, how does a nuclease with
      a single active site cut two DNA strands of opposite polarities to generate a
      double-strand break. In this study, the roles of active-site histidines in
      catalysis were dissected by analysing heterodimeric variants of BfiI lacking the
      histidine in one subunit. These variants revealed a novel mechanism for the
      scission of double-stranded DNA, one that requires a single active site to not
      only switch between strands but also to switch its orientation on the DNA.

PMID- 20047965
TI  - Many sequence-specific chromatin modifying protein-binding motifs show strong
      positional preferences for potential regulatory regions in the Saccharomyces
      cerevisiae genome.
AB  - Initiation and regulation of gene expression is critically dependent on the
      binding of transcriptional regulators, which is often temporal and position
      specific. Many transcriptional regulators recognize and bind specific DNA motifs.
      The length and degeneracy of these motifs results in their frequent occurrence
      within the genome, with only a small subset serving as actual binding sites. By
      occupying potential binding sites, nucleosome placement can specify which
      sequence motif is available for DNA-binding regulatory factors. Therefore, the
      specification of nucleosome placement to allow access to transcriptional
      regulators whenever and wherever required is critical. We show that many DNA
      binding motifs in Saccharomyces cerevisiae show a strong positional preference to
      occur only in potential regulatory regions. Furthermore, using gene ontology
      enrichment tools, we demonstrate that proteins with binding motifs that show the
      strongest positional preference also have a tendency to have chromatin-modifying
      properties and functions. This suggests that some DNA-binding proteins may depend
      on the distribution of their binding motifs across the genome to assist in the
      determination of specificity. Since many of these DNA-binding proteins have
      chromatin remodeling properties, they can alter the local nucleosome structure to
      a more permissive and/or restrictive state, thereby assisting in determining DNA
      binding protein specificity.

PMID- 20047966
TI  - Location analysis for the estrogen receptor-alpha reveals binding to diverse ERE
      sequences and widespread binding within repetitive DNA elements.
AB  - Location analysis for estrogen receptor-alpha (ERalpha)-bound cis-regulatory
      elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)
      on-chip. Here, we present the estrogen response element (ERE) sequences that were
      identified at ERalpha-bound loci and quantify the incidence of ERE sequences
      under two stringencies of detection: <10% and 10-20% nucleotide deviation from
      the canonical ERE sequence. We demonstrate that approximately 50% of all ERalpha
      bound loci do not have a discernable ERE and show that most ERalpha-bound EREs
      are not perfect consensus EREs. Approximately one-third of all ERalpha-bound ERE
      sequences reside within repetitive DNA sequences, most commonly of the AluS
      family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather
      than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets.
      Diverse ERalpha-bound loci were validated using electrophoretic mobility shift
      assay and ChIP-polymerase chain reaction (PCR). The functional significance of
      receptor-bound loci was demonstrated using luciferase reporter assays which
      proved that repetitive element ERE sequences contribute to enhancer function.
      ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to
      these loci in vivo. Our data demonstrate that ERalpha binds to widely variant
      EREs with less sequence specificity than had previously been suspected and that
      binding at repetitive and nonrepetitive genomic targets is favored by specific
      trinucleotide spacers.

PMID- 20047967
TI  - The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a
      pseudouridine-N1-specific methyltransferase.
AB  - Nep1 (Emg1) is a highly conserved nucleolar protein with an essential function in
      ribosome biogenesis. A mutation in the human Nep1 homolog causes Bowen-Conradi
      syndrome-a severe developmental disorder. Structures of Nep1 revealed a dimer
      with a fold similar to the SPOUT-class of RNA-methyltransferases suggesting that
      Nep1 acts as a methyltransferase in ribosome biogenesis. The target for this
      putative methyltransferase activity has not been identified yet. We characterized
      the RNA-binding specificity of Methanocaldococcus jannaschii Nep1 by fluorescence
      and NMR-spectroscopy as well as by yeast three-hybrid screening. Nep1 binds with
      high affinity to short RNA oligonucleotides corresponding to nt 910-921 of M.
      jannaschii 16S rRNA through a highly conserved basic surface cleft along the
      dimer interface. Nep1 only methylates RNAs containing a pseudouridine at a
      position corresponding to a previously identified hypermodified N1-methyl-N3-(3
      amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) in eukaryotic 18S rRNAs.
      Analysis of the methylated nucleoside by MALDI-mass spectrometry, HPLC and NMR
      shows that the methyl group is transferred to the N1 of the pseudouridine. Thus,
      Nep1 is the first identified example of an N1-specific pseudouridine
      methyltransferase. This enzymatic activity is also conserved in human Nep1
      suggesting that Nep1 is the methyltransferase in the biosynthesis of m1acp3-Psi
      in eukaryotic 18S rRNAs.

PMID- 20047968
TI  - SnAvi--a new tandem tag for high-affinity protein-complex purification.
AB  - Systematic tandem-affinity-purification (TAP) of protein complexes was
      tremendously successful in yeast and has changed the general concept of how we
      understand protein function in eukaryotic cells. The transfer of this method to
      other model organisms has been difficult and may require specific adaptations. We
      were especially interested to establish a cell-type-specific TAP system for
      Caenorhabditis elegans, a model animal well suited to high-throughput analysis,
      proteomics and systems biology. By combining the high-affinity interaction
      between in vivo biotinylated target-proteins and streptavidin with the usage of a
      newly identified epitope of the publicly shared SB1 monoclonal antibody we
      created a novel in vivo fluorescent tag, the SnAvi-Tag. We show the versatile
      application of the SnAvi-Tag in Escherichia coli, vertebrate cells and in C.
      elegans for tandem affinity purification of protein complexes, western blotting
      and also for the in vivo sub-cellular localization of labelled proteins.

PMID- 20047969
TI  - Mph1 requires mismatch repair-independent and -dependent functions of MutSalpha
      to regulate crossover formation during homologous recombination repair.
AB  - In budding yeast the DNA helicase Mph1 prevents genome rearrangements during
      ectopic homologous recombination (HR) by suppressing the formation of crossovers
      (COs). Here we show that during ectopic HR repair, the anti-CO function of Mph1
      is intricately associated with the mismatch repair (MMR) factor, MutSalpha. In
      particular, during HR repair using a completely homologous substrate, we reveal
      an MMR-independent function of MutSalpha in generating COs that is specifically
      antagonized by Mph1, but not Sgs1. In contrast, both Mph1 and MutSalpha are
      required to efficiently suppress COs in the presence of a homeologous substrate.
      Mph1 acts redundantly with Sgs1 in this respect since mph1Delta sgs1Delta double
      mutant cells pheno-copy MutSalpha mutants and completely fail to discriminate
      homologous and homeologous sequences during HR repair. However, this defect of
      mph1Delta sgs1Delta cells is not due to an inability to carry out MMR but rather
      is accompanied by elevated levels of gene conversion (GC) and bi-directional GC
      tracts specifically in non-crossover products. Models describing how Mph1,
      MutSalpha and Sgs1 act in concert to suppress genome rearrangements during
      ectopic HR repair are discussed.

PMID- 20047970
TI  - Site-specific chromosomal integration of large synthetic constructs.
AB  - We have developed an effective, easy-to-use two-step system for the site-directed
      insertion of large genetic constructs into arbitrary positions in the Escherichia
      coli chromosome. The system uses lambda-Red mediated recombineering accompanied
      by the introduction of double-strand DNA breaks in the chromosome and a donor
      plasmid bearing the desired insertion fragment. Our method, in contrast to
      existing recombineering or phage-derived insertion methods, allows for the
      insertion of very large fragments into any desired location and in any
      orientation. We demonstrate this method by inserting a 7-kb fragment consisting
      of a venus-tagged lac repressor gene along with a target lacZ reporter into six
      unique sites distributed symmetrically about the chromosome. We also demonstrate
      the universality and repeatability of the method by separately inserting the lac
      repressor gene and the lacZ target into the chromosome at separate locations
      around the chromosome via repeated application of the protocol.

PMID- 20047971
TI  - Tendon augmentation grafts: a systematic review.
AB  - INTRODUCTION: Several biomaterials are available to bridge large tendon defects
      or reinforce tenuous tendon repairs. METHODS: We performed a comprehensive search
      of PubMed, Medline, Cochrane, CINAHL, and Embase databases using various
      combinations of the commercial names of each scaffold and the keywords 'tendon',
      'rotator cuff', 'supraspinatus tendon', 'Achilles tendon', 'scaffold',
      'biomaterials', 'extracellular matrix', 'substitute', and 'devices' over the
      years 1966-2009. All articles relevant to the subject were retrieved, and their
      bibliographies hand searched for further references in the context to
      biomaterials for tendon repair. RESULTS: Many biomaterials are available for
      tendon augmentation. Scanty evidence is available for the use of these scaffolds.
      DISCUSSION: The emerging field of tissue engineering holds the promise to use
      biomaterials for tendon augmentation. Preliminary studies support the idea that
      these biomaterials have the ability to provide an alternative for tendon
      augmentation. However, available data are lacking to allow definitive conclusion
      on the use of biomaterials for tendon augmentation. Additionally, the prevalence
      of postoperative complications encountered with their use varies within the
      different studies. CONCLUSION: Rather than providing strong evidence for or
      against the use of these materials for tendon augmentation, this study instead
      generates potential areas for additional prospective investigation.

PMID- 20047972
TI  - Malignant mesothelioma.
AB  - INTRODUCTION: Mesothelioma is a malignant tumour of the pleura or peritoneum
      caused by asbestos. It is increasing in frequency and the prognosis remains grim,
      with average survival around 1 year. SOURCES OF DATA: Medical literature and
      personal experience. AREAS OF AGREEMENT: Amphibole fibres are far more potent
      than chrysotile in causing mesothelioma. AREAS OF CONTROVERSY: A minority view
      suggests that mesotheliomas in those exposed to chrysotile are caused only by
      tremolite (an amphibole) which contaminates chrysotile. There is a hypothesis,
      for which evidence is weakening, that Simian virus 40 may cause mesothelioma.
      GROWING POINTS: There is emerging evidence of genetic variation in susceptibility
      to fibre carcinogenesis. There are developments in treatment, particularly
      chemotherapy with pemetrexed and cisplatin which prolongs survival and helps
      symptoms. AREAS TIMELY FOR DEVELOPING RESEARCH: Targeted agents for treatment are
      under investigation and may improve the outlook. The role of radical and
      palliative surgery requires clarification.

PMID- 20047973
TI  - Involvement of caspase activation in azaspiracid-induced neurotoxicity in
      neocortical neurons.
AB  - Azaspiracids (AZAs) are a novel group of marine phycotoxins that have been
      associated with severe human intoxication. We found that AZA-1 exposure increased
      lactate dehydrogense (LDH) efflux in murine neocortical neurons. AZA-1 also
      produced nuclear condensation and stimulated caspase-3 activity with an half
      maximal effective concentration (EC(50)) value of 25.8 nM. These data indicate
      that AZA-1 triggers neuronal death in neocortical neurons by both necrotic and
      apoptotic mechanisms. An evaluation of the structure-activity relationships of
      AZA analogs on LDH efflux and caspase-3 activation demonstrated that the full
      structure of AZAs was required to produce necrotic or apoptotic cell death. The
      similar potencies of AZA-1 to stimulate LDH efflux and caspase-3 activation and
      the parallel structure-activity relationships of azaspiracid analogs in the two
      assays are consistent with a common molecular target for both responses. To
      explore the molecular mechanism for AZA-1-induced neurotoxicity, we assessed the
      influence of AZA-1 on Ca(2+) homeostasis. AZA-1 suppressed spontaneous Ca(2+)
      oscillations (EC(50) = 445 nM) in neocortical neurons. A distinct structure
      activity profile was found for inhibition of Ca(2+) oscillations where both the
      full structure as well as analogs containing only the FGHI domain attached to a
      phenyl glycine methyl ester moiety were potent inhibitors. The molecular targets
      for inhibition of spontaneous Ca(2+) oscillations and neurotoxicity may therefore
      differ. The caspase protease inhibitor Z-VAD-FMK produced a complete elimination
      of AZA-1-induced LDH efflux and nuclear condensation in neocortical neurons.
      Although the molecular target for AZA-induced neurotoxicity remains to be
      established, these results demonstrate that the observed neurotoxicity is
      dependent on a caspase signaling pathway.

PMID- 20047974
TI  - Now's the time to find biomarkers on purpose.

PMID- 20047975
TI  - Lung cancer and occupation in a population-based case-control study.
AB  - The authors examined the relation between occupation and lung cancer in the
      large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE)
      case-control study. In 2002-2005 in the Lombardy region of northern Italy, 2,100
      incident lung cancer cases and 2,120 randomly selected population controls were
      enrolled. Lifetime occupational histories (industry and job title) were coded by
      using standard international classifications and were translated into occupations
      known (list A) or suspected (list B) to be associated with lung cancer. Smoking
      adjusted odds ratios and 95% confidence intervals were calculated with logistic
      regression. For men, an increased risk was found for list A (177 exposed cases
      and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and
      most occupations therein. No overall excess was found for list B with the
      exception of filling station attendants and bus and truck drivers (men) and
      launderers and dry cleaners (women). The authors estimated that 4.9% (95%
      confidence interval: 2.0, 7.8) of lung cancers in men were attributable to
      occupation. Among those in other occupations, risk excesses were found for metal
      workers, barbers and hairdressers, and other motor vehicle drivers. These results
      indicate that past exposure to occupational carcinogens remains an important
      determinant of lung cancer occurrence.

PMID- 20047976
TI  - A comparison of sample size and power in case-only association studies of gene
      environment interaction.
AB  - Assuming continuous, normally distributed environmental and categorical genotype
      variables, the authors compare 6 case-only designs for tests of association in
      gene-environment interaction. Novel tests modeling the environmental variable as
      either the response or the predictor and allowing a genetic variable with
      multiallelic variants are included. The authors show that tests imposing the same
      genotypic pattern of inheritance perform similarly regardless of whether genotype
      is the response variable or the predictor variable. The novel tests using the
      genetic variable as the response variable are advantageous because they are
      robust to non-normally distributed environmental exposures. Dominance deviance
      deviation from additivity in the main or interaction effects-is key to test
      performance: When it is zero or modest, tests searching for a trend with
      increasing risk alleles are optimal; when it is large, tests for genotypic
      effects are optimal. However, the authors show that dominance deviance is
      attenuated when it is observed at a proxy locus, which is common in genome-wide
      association studies, so large dominance deviance is likely to be rare. The
      authors conclude that the trend test is the appropriate tool for large-scale
      association scans where the true gene-environment interaction model is unknown.
      The common practice of assuming a dominant pattern of inheritance can cause
      serious losses of power in the presence of any recessive, or modest dominant,
      effects.

PMID- 20047978
TI  - Correlates for human papillomavirus vaccination of adolescent girls and young
      women in a managed care organization.
AB  - The authors studied the characteristics of those who initiated the human
      papillomavirus (HPV) vaccine versus those who did not. Female members of Kaiser
      Permanente Southern California aged 9-26 years were identified and assessed for
      HPV vaccination between October 2006 and March 2008. Multivariable log-binomial
      regression was used to examine the association of the following factors with
      vaccine initiation: 1) demographics, 2) provider characteristics, 3) health care
      utilization, 4) women's health-related conditions, and 5) selected immune-related
      conditions. The study included 285,265 females. All analyses were stratified by 2
      age groups: 9-17 years and 18-26 years. Black race (relative risk (RR)(9-17
      years) = 0.93, RR(18-26 years) = 0.82), having a male primary care provider (RR(9
      17 years) = 0.93, RR(18-26 years) = 0.84), and history of hospitalizations were
      associated with a lower likelihood of vaccine initiation. Higher neighborhood
      income level, physician office visits, and history of influenza vaccination (RR(9
      17 years) = 1.20, RR(18-26 years) = 1.34) were associated with higher HPV vaccine
      uptake. Those with a history of sexually transmitted diseases were more likely
      and those with immune-related conditions were not less likely to initiate the HPV
      vaccine. These findings are helpful for interpreting the results of observational
      safety studies and providing insights for developing targeted HPV vaccination
      programs.

PMID- 20047979
TI  - Superiority of SDAI over DAS-28 in assessment of remission in rheumatoid
      arthritis patients using power Doppler ultrasonography as a gold standard.
AB  - OBJECTIVE: To investigate the accuracy of composite scores in classifying RA
      patients who are in remission using the absence of inflammatory activity detected
      by ultrasound (US) as a gold standard. METHODS: Ninety-seven RA patients who were
      classified by their rheumatologists as being in remission were studied. Disease
      activity was assessed by the DAS-28 and simplified disease activity index (SDAI).
      US examination was performed in mode B and power Doppler (PD) in 42 joints.
      RESULTS: Synovial hypertrophy (SH) and PD were present in 92 (94.8%) and 41
      (42.3%) patients. If we consider 'remission' to be the absence of joints with PD
      signal, no differences were found by DAS-28 between patients in remission and
      those not in remission, although differences were present by SDAI. We then
      calculated the sensitivity (S), specificity (Sp) and positive likelihood ratio
      (LR) of different SDAI cut-off points to predict absence of PD signal. SDAI < 5
      had an S of 65% (95% CI 52, 76), Sp of 55% (95% CI 39, 69) and LR of 1.45 (95% CI
      0.98, 2.15), whereas SDAI < 3.3 had an S of 57% (95% CI 44, 69), Sp of 74% (95%
      CI 58, 85) and LR of 2.24 (95% CI 1.25, 4.01). CONCLUSIONS: Our results suggest
      that the SDAI classification of remission is closer to the concept of an absence
      of inflammatory activity, as defined by the absence of positive PD signal by US.

PMID- 20047977
TI  - Tumor necrosis factor (TNF) and lymphotoxin-alpha (LTA) polymorphisms and risk of
      non-Hodgkin lymphoma in the InterLymph Consortium.
AB  - In an International Lymphoma Epidemiology Consortium pooled analysis,
      polymorphisms in 2 immune-system-related genes, tumor necrosis factor (TNF) and
      interleukin-10 (IL10), were associated with non-Hodgkin lymphoma (NHL) risk.
      Here, 8,847 participants were added to previous data (patients diagnosed from
      1989 to 2005 in 14 case-control studies; 7,999 cases, 8,452 controls) for testing
      of polymorphisms in the TNF -308G>A (rs1800629), lymphotoxin-alpha (LTA) 252A>G
      (rs909253), IL10 -3575T>A (rs1800890, rs1800896), and nucleotide-binding
      oligomerization domain containing 2 (NOD2) 3020insC (rs2066847) genes. Odds
      ratios were estimated for non-Hispanic whites and several ethnic subgroups using
      2-sided tests. Consistent with previous findings, odds ratios were increased for
      "new" participant TNF -308A carriers (NHL: per-allele odds ratio (OR(allelic)) =
      1.10, P(trend) = 0.001; diffuse large B-cell lymphoma (DLBCL): OR(allelic) =
      1.23, P(trend) = 0.004). In the combined population, odds ratios were increased
      for TNF -308A carriers (NHL: OR(allelic) = 1.13, P(trend) = 0.0001; DLBCL:
      OR(allelic) = 1.25, P(trend) = 3.7 x 10(-6); marginal zone lymphoma: OR(allelic)
      = 1.35, P(trend) = 0.004) and LTA 252G carriers (DLBCL: OR(allelic) = 1.12,
      P(trend) = 0.006; mycosis fungoides: OR(allelic) = 1.44, P(trend) = 0.015). The
      LTA 252A>G/TNF -308G>A haplotype containing the LTA/TNF variant alleles was
      strongly associated with DLBCL (P = 2.9 x 10(-8)). Results suggested associations
      between IL10 -3575T>A and DLBCL (P(trend) = 0.02) and IL10 -1082A>G and mantle
      cell lymphoma (P(trend) = 0.04). These findings strengthen previous results for
      DLBCL and the LTA 252A>G/TNF -308A locus and provide robust evidence that these
      TNF/LTA gene variants, or others in linkage disequilibrium, are involved in NHL
      etiology.

PMID- 20047980
TI  - Autoimmunity and recurrent infections in partial complement C3 immunodeficiency.

PMID- 20047981
TI  - Association between transforming growth factor-beta1 T869C polymorphism and
      rheumatoid arthritis: a meta-analysis.
AB  - OBJECTIVE: The results of studies on association between TGF-beta1 T869C
      polymorphism and susceptibility to RA are controversial. The absence of a
      replication of linkage might be due to different ethnicities. The aim of this
      study was to perform a preliminary investigation on the effect size of TGF-beta1
      T869C polymorphism on RA susceptibility through a meta-analysis. METHODS: Case
      control studies on the association of TGF-beta1 T869C with RA were searched up to
      March 2009, and the genotype frequencies in the control group were found to be
      consistent with the Hardy-Weinberg equilibrium. The effect summary odds ratio
      (OR) and 95% CIs were obtained. Publication bias was tested by funnel plot with
      Egger's regression test, and heterogeneity was assessed. RESULTS: Seven studies
      comprising 1122 cases and 1132 controls were included. Heterogeneity was observed
      (chi(2 )= 17.16; P = 0.009). Under the random effects model, the common OR was
      1.38 (95% CI 0.95, 2.01; P = 0.09). In the subgroup meta-analysis, there was an
      association between TGF-beta1 T869C polymorphism and RA in the people of Asian
      descent (OR = 1.93; 95% CI 1.42, 2.62; P < 0.0001), but not in the people of non
      Asian descent (OR = 0.88; 95% CI 0.65, 1.19; P = 0.41). There was no evidence of
      publication bias according to Funnel plot and Egger's regression test (a = 4.778;
      P = 0.14). CONCLUSIONS: There was heterogeneity between studies, and no clear
      evidence of an association on a worldwide population was observed. Subgroup
      analysis results suggest that TGF-beta1 T869C might play a role in RA
      susceptibility for Asians but not for non-Asians. Further studies are required
      for definite conclusions.

PMID- 20047982
TI  - Long-term improvement of lipid profile in patients with refractory systemic lupus
      erythematosus treated with B-cell depletion therapy: a retrospective
      observational study.
AB  - OBJECTIVE: Lipid abnormalities contribute to the increased risk of premature
      atherosclerosis in patients with SLE. This study was undertaken to investigate
      changes in lipid profile after B-cell depletion therapy (BCDT) in patients with
      active SLE who had failed standard immunosuppressive therapy. METHODS: Twelve
      patients with refractory SLE treated with BCDT based on rituximab (two biweekly
      infusions of 1 g) were examined. Lipid profile and lupus activity were measured
      before the infusions and 1 year later. The control group consisted of 26 age- and
      sex-matched lupus patients not treated with BCDT. RESULTS: In the study group,
      the mean levels of total, high-density lipoprotein (HDL) and low-density
      lipoprotein cholesterols were 4.6, 1.4 and 2.4 mmol/l at baseline and changed to
      4.1, 1.6 and 2.0 mmol/l (P = NS, P = 0.04 and P = NS) at 1 year, respectively.
      The atherogenic index was 3.8 at baseline and decreased to 2.7 (P = 0.02). The
      triglyceride (TG) level was 2.1 mmol/l at baseline and decreased to 1.3 mmol/l (P
      = 0.04). BCDT was followed by a significant decrease in global BILAG scores and a
      drop in the mean dose of prednisolone at 1 year (P = 0.01). Reduction in disease
      activity was significantly associated with a reduction in total cholesterol and
      TG levels and an increase in HDL cholesterol levels. In the control group, there
      were no differences in any of the lipid determinations over a 1-year period.
      CONCLUSION. This provisional observational study suggests a favourable long-term
      effect of BCDT on the lipid profile of patients with refractory SLE, which
      correlated with decreasing activity of the disease.

PMID- 20047983
TI  - Expression analysis of the 3 G-protein subunits, Galpha, Gbeta, and Ggamma, in
      the olfactory receptor organs of adult Drosophila melanogaster.
AB  - In many species, olfactory transduction is triggered by odorant molecules that
      interact with olfactory receptors coupled to heterotrimeric G-proteins. The role
      of G-protein-linked transduction in the olfaction of Drosophila is currently
      under study. Here, we supply a thorough description of the expression in the
      olfactory receptor organs (antennae and maxillary palps) of all known Drosophila
      melanogaster genes that encode for G-proteins. Using RT-polymerase chain
      reaction, we analyzed 6 Galpha (G(s), G(i), G(q), G(o), G(f), and concertina), 3
      Gbeta (G(beta5), G(beta13F), and G(beta76C)), and 2 Ggamma genes (G(gamma1) and
      G(gamma30A)). We found that all Galpha protein-encoding genes showed expression
      in both olfactory organs, but G(f) mRNA was not detected in palps. Moreover, all
      the Gbeta and Ggamma genes are expressed in antennae and palps, except for
      G(beta76C). To gain insight into the hypothesis of different G-protein subunits
      mediating differential signaling in olfactory receptor neurons (ORNs), we
      performed immunohistochemical studies to observe the expression of several Galpha
      and Gbeta proteins. We found that Gs, Gi, Gq, and G(beta13F) subunits displayed
      generalized expression in the antennal tissue, including ORNs support cells and
      glial cells. Finally, complete coexpression was found between Gi and Gq, which
      are mediators of the cyclic adenosine monophosphate and IP3 transduction
      cascades, respectively.

PMID- 20047984
TI  - Adult children's problems and successes: implications for intergenerational
      ambivalence.
AB  - Ambivalence theory suggests that parents experience ambivalence due to
      conflicting desires to help children in need and to launch children into
      adulthood. This study examined parents' reports of their adult children's
      problems and successes and implications for ambivalence. Participants aged 40-60
      years (302 men and 331 women from different families) reported on up to 3 of
      their adult children (N = 1,251). Men and women differentiated among children in
      ratings of problems, successes, and ambivalence. Men and not women reported
      greater ambivalence regarding children with more physical-emotional problems and
      less career success. Men and women reported greater ambivalence regarding
      children with less relationship success. Consistent with ambivalence theory,
      individuals feel more ambivalent regarding problematic and less successful
      children but men's ambivalence appears to be more sensitive to their children's
      problems and successes than women's ambivalence.

PMID- 20047985
TI  - Adult age differences and the role of cognitive resources in perceptual-motor
      skill acquisition: application of a multilevel negative exponential model.
AB  - The effects of advanced age and cognitive resources on the course of skill
      acquisition are unclear, and discrepancies among studies may reflect limitations
      of data analytic approaches. We applied a multilevel negative exponential model
      to skill acquisition data from 80 trials (four 20-trial blocks) of a pursuit
      rotor task administered to healthy adults (19-80 years old). The analyses
      conducted at the single-trial level indicated that the negative exponential
      function described performance well. Learning parameters correlated with measures
      of task-relevant cognitive resources on all blocks except the last and with age
      on all blocks after the second. Thus, age differences in motor skill acquisition
      may evolve in 2 phases: In the first, age differences are collinear with
      individual differences in task-relevant cognitive resources; in the second, age
      differences orthogonal to these resources emerge.

PMID- 20047986
TI  - Recognition memory and the hippocampus: A test of the hippocampal contribution to
      recollection and familiarity.
AB  - It has been suggested that the hippocampus selectively supports recollection and
      that adjacent cortex in the medial temporal lobe can support familiarity.
      Alternatively, it has been suggested that the hippocampus supports both
      recollection and familiarity. We tested these suggestions by assessing the
      performance of patients with hippocampal lesions on recognition memory tests that
      differ in the extent to which recollection and familiarity contribute to the
      recognition decision. When targets and foils are highly similar, prior evidence
      suggests that, on a forced-choice test in which targets are presented together
      with highly similar, corresponding foils (the FC-C format), performance is
      supported primarily by familiarity. By contrast, when targets are presented
      together with foils that are similar to other targets (the FC-NC format) or when
      memory is tested in a yes/no (Y/N) format, performance is based much more
      strongly on recollection. Accordingly, a finding that hippocampal damage impaired
      both Y/N recognition and FC-NC recognition but spared FC-C recognition would
      suggest that the hippocampus selectively supports recollection. We administered
      Y/N, FC-C, and FC-NC tests to five memory-impaired patients with circumscribed
      hippocampal lesions and 14 controls. The patients were impaired on all three
      types of recognition test, and there was no indication that the patients were
      disproportionately benefited or disproportionately impaired on any test. This
      pattern of performance suggests that the hippocampus supports both recollection
      and familiarity.

PMID- 20047987
TI  - Evaluation of 4',6-diamidino-2-phenylindole as a fluorescent probe substrate for
      rapid assays of the functionality of human multidrug and toxin extrusion
      proteins.
AB  - Multidrug and toxin extrusion protein 1 (MATE1) and MATE2-K are organic
      cation/H(+) antiporters that have recently been identified and suggested to be
      responsible for the brush border secretory transport of many cationic drugs in
      renal tubules. We here report our finding that 4',6-diamidino-2-phenylindole
      (DAPI) can be used as a probe substrate for rapid assays of the functionality of
      the human MATEs, hMATE1, and hMATE2-K, by taking advantage of its fluorescent
      nature. The specific cellular uptakes of DAPI by cloned hMATE1 and hMATE2-K,
      which were assessed by fluorescence intensity, were found to be rapid and
      saturable with the Michaelis constants of 1.13 and 3.16 microM, respectively,
      indicating that DAPI is a good substrate of both hMATEs. It was found that many
      organic cations inhibit the specific uptake of DAPI by hMATE1 and hMATE2-K, and
      the extents of inhibition are in good correlation with those of inhibition of the
      specific uptake of [(3)H]cimetidine as a typical substrate, indicating comparable
      performances of both substrates as probes in identifying inhibitors. Thus, DAPI
      can be an alternative probe substrate that enables fluorometric rapid assays of
      the functionality of both hMATEs. It was also found that the other major renal
      organic cation transporters, human organic cation transporter 2 (hOCT2), hOCT3,
      human novel organic cation transporter 1 (hOCTN1), and hOCTN2, cannot transport
      DAPI, although hOCT1, which is mainly expressed in the liver, can. Therefore, the
      DAPI uptake assay can be a method specific to the hMATEs among organic cation
      transporters in the human kidney.

PMID- 20047988
TI  - Absorption, distribution, and biliary excretion of cafestol, a potent cholesterol
      elevating compound in unfiltered coffees, in mice.
AB  - Cafestol is a diterpene present in unfiltered coffees. It is the most potent
      cholesterol-elevating compound present in the human diet. However, the precise
      mechanisms underlying this effect are still unclear. In contrast, cafestol is
      also known as a hepatoprotective compound, which is likely to be related to the
      induction of glutathione biosynthesis and conjugation. In the present study, we
      investigated whole-body distribution, biliary excretion, and portal
      bioavailability of cafestol in mice. First, dissection was used to study
      distribution. Five hours after an oral dose with (3)H-labeled cafestol, most
      activity was found in small intestine, liver, and bile. These results were
      confirmed by quantitative whole-body autoradiography in a time course study,
      which also showed elimination of all radioactivity within 48 h after
      administration. Next, radiolabeled cafestol was dosed intravenously to bile duct
      cannulated mice. Five hours after the dose 20% of the radioactivity was found in
      bile. Bile contained several metabolites but no parent compound. After intestinal
      administration of radioactive cafestol to portal vein-cannulated mice, cafestol
      was shown to be rapidly absorbed into the portal vein as the parent compound, a
      glucuronide, and an unidentified metabolite. From the presence of a glucuronide
      in bile that can be deconjugated by a bacterial enzyme and the prolonged
      absorption of parent compound from the gastrointestinal tract, we hypothesized
      that cafestol undergoes enterohepatic cycling. Together with our earlier
      observation that epoxidation of the furan ring occurs in liver, these findings
      merit further research on the process of accumulation of this coffee ingredient
      in liver and intestinal tract.

PMID- 20047989
TI  - Thermodynamic characterization of naturally occurring RNA tetraloops.
AB  - Although tetraloops are one of the most frequently occurring secondary structure
      motifs in RNA, less than one-third of the 30 most frequently occurring RNA
      tetraloops have been thermodynamically characterized. Therefore, 24 stem-loop
      sequences containing common tetraloops were optically melted, and the
      thermodynamic parameters DeltaH degrees , DeltaS degrees , DeltaG degrees (37,)
      and T(M) for each stem-loop were determined. These new experimental values, on
      average, are 0.7 kcal/mol different from the values predicted for these
      tetraloops using the model proposed by Vecenie CJ, Morrow CV, Zyra A, Serra MJ.
      2006. Biochemistry 45: 1400-1407. The data for the 24 tetraloops reported here
      were then combined with the data for 28 tetraloops that were published
      previously. A new model, independent of terminal mismatch data, was derived to
      predict the free energy contribution of previously unmeasured tetraloops. The
      average absolute difference between the measured values and the values predicted
      using this proposed model is 0.4 kcal/mol. This new experimental data and updated
      predictive model allow for more accurate calculations of the free energy of RNA
      stem-loops containing tetraloops and, furthermore, should allow for improved
      prediction of secondary structure from sequence. It was also shown that
      tetraloops within the sequence 5'-GCCNNNNGGC-3' are, on average, 0.6 kcal/mol
      more stable than the same tetraloop within the sequence 5'-GGCNNNNGCC-3'. More
      systemic studies are required to determine the full extent of non-nearest
      neighbor effects on tetraloop stability.

PMID- 20047990
TI  - Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection.
AB  - In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through
      their capacity to regulate both host and viral genes. Recent reports have
      demonstrated that specific miRNAs change in expression level upon infection and
      can impact viral production and infectivity. It is clear that miRNAs are an
      integral component of viral-host interactions, and it is likely that both host
      and virus contain mechanisms to regulate miRNA expression and/or activity. To
      date, little is known about the mechanisms by which miRNAs are regulated in viral
      infection. Here we report the rapid down-regulation of miR-27a in multiple mouse
      cell lines as well as primary macrophages upon infection with the murine
      cytomegalovirus. Down-regulation of miR-27a occurs independently from two other
      miRNAs, miR-23a and miR-24, located within the same genomic cluster, and analysis
      of pri-miRNA levels suggest that regulation occurs post-transcriptionally. miR
      27b, a close homolog of miR-27a (20/21 nucleotide identity), also decreases upon
      infection, and we demonstrate that both miR-27a and miR-27b exert an antiviral
      function upon over-expression. Drug sensitivity experiments suggest that virus
      entry is not sufficient to induce the down-regulation of miR-27 and that the
      mechanism requires synthesis of RNA. Altogether, our findings indicate that miR
      27a and miR-27b have antiviral activity against MCMV, and that either the virus
      or the host encodes molecule(s) for regulating miR-27 accumulation, most likely
      by inducing the rapid decay of the mature species.

PMID- 20047991
TI  - Diagnostic accuracy of 320-row multidetector computed tomography coronary
      angiography in the non-invasive evaluation of significant coronary artery
      disease.
AB  - AIMS: Multidetector computed tomography coronary angiography (CTA) has emerged as
      a feasible imaging modality for non-invasive assessment of coronary artery
      disease (CAD). Recently, 320-row CTA systems were introduced, with 16 cm
      anatomical coverage, allowing image acquisition of the entire heart within a
      single heart beat. The aim of the present study was to assess the diagnostic
      accuracy of 320-row CTA in patients with known or suspected CAD. METHODS AND
      RESULTS: A total of 64 patients (34 male, mean age 61 +/- 16 years) underwent CTA
      and invasive coronary angiography. All CTA scans were evaluated for the presence
      of obstructive coronary stenosis by a blinded expert, and results were compared
      with quantitative coronary angiography. Four patients were excluded from initial
      analysis due to non-diagnostic image quality. Sensitivity, specificity, and
      positive and negative predictive values to detect > or =50% luminal narrowing on
      a patient basis were 100, 88, 92, and 100%, respectively. Moreover, sensitivity,
      specificity, and positive and negative predictive values to detect > or =70%
      luminal narrowing on a patient basis were 94, 95, 88, and 98%, respectively. With
      inclusion of non-diagnostic imaging studies, sensitivity, specificity, and
      positive and negative predictive values to detect > or =50% luminal narrowing on
      a patient basis were 100, 81, 88, and 100%, respectively. CONCLUSION: The current
      study shows that 320-row CTA allows accurate non-invasive assessment of
      significant CAD.

PMID- 20047992
TI  - Unusual unmasking of Brugada syndrome electrocardiographic pattern during
      ajmaline test by leaning forward: a case report.

PMID- 20047993
TI  - Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts
      and myocytes?
AB  - AIMS: Indoxyl sulfate (IS) is a uraemic toxin found at high concentration in
      patients with chronic kidney disease (CKD) co-morbid with chronic heart failure
      (CHF). The aim of this study was to determine direct effects of IS on cardiac
      cells as well as the pro-inflammatory effect of IS. METHODS AND RESULTS: Indoxyl
      sulfate significantly increased neonatal rat cardiac fibroblast collagen
      synthesis (by 145.7% vs. control, P < 0.05) and myocyte hypertrophy (by 134.5%
      vs. control, P < 0.001) as determined by (3)H-proline or (3)H-leucine
      incorporation, respectively. Indoxyl sulfate stimulated tumour necrosis factor
      alpha, interleukin-6 (IL-6), and IL-1beta mRNA expression in THP-1 cells as
      quantified by RT-PCR. Both p38 (RWJ-67657) and MEK1/2 (U0126) inhibitors
      suppressed all these effects by IS. Furthermore, western blot analysis showed
      that IS activated mitogen-activated protein kinase (MAPK) (p38, p42/44) and
      nuclear factor-kappa B (NFkappaB) pathways. 3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay showed that IS exerted its effects without
      affecting cell viability. CONCLUSION: This study has, for the first time,
      demonstrated that IS has pro-fibrotic, pro-hypertrophic, and pro-inflammatory
      effects, indicating that IS might play an important role in adverse cardiac
      remodelling mediated via activation of the p38 MAPK, p42/44 MAPK, and NFkappaB
      pathways. Targeting reduction of IS and/or the pathways it activates may
      represent a novel therapeutic approach to the management of CHF with concomitant
      CKD.

PMID- 20047994
TI  - Risk stratification of patients with aortic stenosis.
AB  - Aortic stenosis (AS) is now the most common indication for valve replacement in
      Europe and North America, with an ever increasing disease prevalence due to the
      ageing population (Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C,
      Levang AW, Tornos P, Vanoverschelde JL, Vermeer F, Boersma E, Ravaud P, Vahanian
      A. A prospective survey of patients with valvular heart disease in Europe: the
      Euro Heart Survey on valvular heart disease. Eur Heart J 2003; 24:1231-1243). The
      recent introduction of transcatheter aortic valve implantation has renewed
      interest in the optimal approach to patient management. Decision making in
      valvular heart disease necessitates a careful evaluation of the risk-to-benefit
      ratio, considering both the results of intervention and the severity-adjusted
      risk of adverse outcomes without intervention.

PMID- 20047995
TI  - Tumorigenicity of the miR-17-92 cluster distilled.
AB  - The miR-17-92 gene cluster, with its six different mature microRNAs (miRNAs), has
      an established oncogenic function. However, the oncogenic contribution of each
      individual miRNA in the cluster has not been assigned. Two studies published in
      the December 15, 2009, issue of Genes & Development by Mu and colleagues (pp.
      2806-2811) and Olive and colleagues (pp. 2839-2849) dissected the miR-17-92
      cluster to its individual miRNA components and identified their relative
      contributions to oncogenic transformation in mouse model systems.

PMID- 20047996
TI  - Leaping forks at inverted repeats.
AB  - Genome rearrangements are often associated with genome instability observed in
      cancer and other pathological disorders. Different types of repeat elements are
      common in genomes and are prone to instability. S-phase checkpoints,
      recombination, and telomere maintenance pathways have been implicated in
      suppressing chromosome rearrangements, but little is known about the molecular
      mechanisms and the chromosome intermediates generating such genome-wide
      instability. In the December 15, 2009, issue of Genes & Development, two studies
      by Paek and colleagues (2861-2875) and Mizuno and colleagues (pp. 2876-2886),
      demonstrate that nearby inverted repeats in budding and fission yeasts recombine
      spontaneously and frequently to form dicentric and acentric chromosomes. The
      recombination mechanism underlying this phenomenon does not appear to require
      double-strand break formation, and is likely caused by a replication mechanism
      involving template switching.

PMID- 20047997
TI  - Switching the mechanism of mating type switching: a domesticated transposase
      supplants a domesticated homing endonuclease.
AB  - Programmed DNA rearrangements are critical for the development of many organisms
      and, intriguingly, can be catalyzed by domesticated mobile genetic elements. In
      this issue of Genes & Development, Barsoum and colleagues (pp. 33-44) demonstrate
      that, in the budding yeast Kluyveromyces lactis, a DNA rearrangement associated
      with mating type switching requires a domesticated transposase and occurs through
      a mechanism distinct from that in the related yeast, Saccharomyces cerevisiae.
      Thus, mechanisms for mating type switching have evolved multiple times,
      indicating the relative ease with which mobile genetic elements can be captured.

PMID- 20047998
TI  - C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control
      in mammals.
AB  - Upstream ORFs (uORFs) are translational control elements found predominantly in
      transcripts of key regulatory genes. No mammalian genetic model exists to
      experimentally validate the physiological relevance of uORF-regulated translation
      initiation. We report that mice deficient for the CCAAT/enhancer-binding protein
      beta (C/EBPbeta) uORF initiation codon fail to initiate translation of the
      autoantagonistic LIP (liver inhibitory protein) C/EBPbeta isoform.
      C/EBPbeta(DeltauORF) mice show hyperactivation of acute-phase response genes,
      persistent repression of E2F-regulated genes, delayed and blunted S-phase entry
      of hepatocytes after partial hepatectomy, and impaired osteoclast
      differentiation. These data and the widespread prevalence of uORFs in mammalian
      transcriptomes suggest a comprehensive role of uORF-regulated translation in
      (patho)physiology.

PMID- 20047999
TI  - Spred1, a negative regulator of Ras-MAPK-ERK, is enriched in CNS germinal zones,
      dampens NSC proliferation, and maintains ventricular zone structure.
AB  - Neural stem cells (NSCs) have great potential for self-renewal, which must be
      tightly regulated to generate appropriate cell numbers during development and to
      prevent tumor formation. The Ras-MAPK-ERK pathway affects mitogen-stimulated
      proliferation, and negative regulators are likely to be important for keeping
      self-renewal in check. Sprouty-related protein with an EVH1 domain (Spred1) is a
      recently discovered negative Ras-MAPK-ERK regulator linked to a neurofibromatosis
      1 (NF-1)-like human syndrome; however, its role in CNS development has not been
      explored. We show that Spred1 is highly enriched in CNS germinal zones during
      neurogenesis. Spred1 knockdown increases NSC self-renewal and progenitor
      proliferation cell-autonomously, and overexpression causes premature
      differentiation. Surprisingly, Spred1 knockdown in vivo in the embryonic mouse
      forebrain frequently resulted in periventricular heterotopia, developmental
      abnormalities often associated with mutations in genes in the vesicular
      trafficking pathway that cause disruption of germinal zones and impair cell
      migration. In cortical progenitor cells, Spred1 localizes within distinct
      vesicles, indicating a potential role in transport. Spred1 knockdown gradually
      leads to disruption of the apical ventricular zone and loss of radial glia
      alignment. This impairs late neuronal migration, resulting in the formation of
      periventricular masses. Thus, Spred1 is critical for normal cortical development,
      as it modulates progenitor self-renewal/proliferation and helps maintain the
      integrity and organization of germinal zones.

PMID- 20048000
TI  - Genetic and biochemical definition of the Hedgehog receptor.
AB  - Although the transporter-like protein Patched (Ptc) is genetically implicated in
      reception of the extracellular Hedgehog (Hh) protein signal, a clear definition
      of the Hh receptor is complicated by the existence of additional Hh-binding
      proteins and, in Drosophila, by the lack of physical evidence for direct binding
      of Hh to Ptc. Here we show that activity of Ihog (Interference hedgehog), or of
      its close relative Boi (Brother of Ihog), is absolutely required for Hh
      biological response and for sequestration of the Hh protein to limit long-range
      signaling. We demonstrate that Ihog interacts directly with Ptc, is required for
      presentation of Ptc on the cell surface, and that Ihog and Ptc are both required
      for high-affinity Hh binding. On the basis of their joint roles in ligand
      binding, signal transduction, and receptor trafficking, we conclude that Ihog and
      Ptc together constitute the Drosophila Hh receptor.

PMID- 20048001
TI  - A coordinated phosphorylation by Lats and CK1 regulates YAP stability through
      SCF(beta-TRCP).
AB  - The Yes-associated protein (YAP) transcription coactivator is a key regulator of
      organ size and a candidate human oncogene. YAP is inhibited by the Hippo pathway
      kinase cascade, at least in part via phosphorylation of Ser 127, which results in
      YAP 14-3-3 binding and cytoplasmic retention. Here we report that YAP is
      phosphorylated by Lats on all of the five consensus HXRXXS motifs.
      Phosphorylation of Ser 381 in one of them primes YAP for subsequent
      phosphorylation by CK1delta/epsilon in a phosphodegron. The phosphorylated
      phosphodegron then recruits the SCF(beta-TRCP) E3 ubiquitin ligase, which
      catalyzes YAP ubiquitination, ultimately leading to YAP degradation. The
      phosphodegron-mediated degradation and the Ser 127 phosphorylation-dependent
      translocation coordinately suppress YAP oncogenic activity. Our study identified
      CK1delta/epsilon as new regulators of YAP and uncovered an intricate mechanism of
      YAP regulation by the Hippo pathway via both S127 phosphorylation-mediated
      spatial regulation (nuclear-cytoplasmic shuttling) and the phosphodegron-mediated
      temporal regulation (degradation).

PMID- 20048002
TI  - Multifunctional factor ENY2 is associated with the THO complex and promotes its
      recruitment onto nascent mRNA.
AB  - Metazoan E(y)2/ENY2 is a multifunctional protein important for transcription
      activation and mRNA export, being a component of SAGA/TFTC and the mRNA export
      complex AMEX. Here, we show that ENY2 in Drosophila is also stably associated
      with THO, the complex involved in mRNP biogenesis. The ENY2-THO complex is
      required for normal Drosophila development, functioning independently on SAGA and
      AMEX. ENY2 and THO arrive on the transcribed region of the hsp70 gene after its
      activation, and ENY2 plays an important role in THO recruitment. ENY2 and THO
      show no direct association with elongating RNA polymerase II. Recruitment of ENY2
      and THO occurs by their loading onto nascent mRNA, apparently immediately after
      its synthesis, while the AMEX component Xmas-2 is loaded onto mRNA at a later
      stage. Knockdown of either ENY2 or THO, but not SAGA or AMEX, affects the
      processing of the transcript's 3' end. Thus, ENY2, as a shared subunit of several
      protein complexes governing the sequential steps of gene expression, plays an
      important role in the coordination of these steps.

PMID- 20048003
TI  - Regulatory elements in eIF1A control the fidelity of start codon selection by
      modulating tRNA(i)(Met) binding to the ribosome.
AB  - eIF1A is the eukaryotic ortholog of bacterial translation initiation factor IF1,
      but contains a helical domain and long unstructured N-terminal tail (NTT) and C
      terminal tail (CTT) absent in IF1. Here, we identify elements in these accessory
      regions of eIF1A with dual functions in binding methionyl initiator tRNA (Met
      tRNA(i)(Met)) to the ribosome and in selecting AUG codons. A pair of repeats in
      the eIF1A CTT, dubbed Scanning Enhancer 1 (SE1) and SE2, was found to stimulate
      recruitment of Met-tRNA(i)(Met) in the ternary complex (TC) with eIF2.GTP and
      also to block initiation at UUG codons. In contrast, the NTT and segments of the
      helical domain are required for the elevated UUG initiation occurring in SE
      mutants, and both regions also impede TC recruitment. Remarkably, mutations in
      these latter elements, dubbed scanning inhibitors SI1 and SI2, reverse the
      defects in TC loading and UUG initiation conferred by SE substitutions, showing
      that the dual functions of SE elements in TC binding and UUG suppression are
      mechanistically linked. It appears that SE elements enhance TC binding in a
      conformation conducive to scanning but incompatible with initiation, whereas SI
      elements destabilize this conformation to enable full accommodation of Met
      tRNA(i)(Met) in the P site for AUG selection.

PMID- 20048004
TI  - Why the pursuit of excellence matters.

PMID- 20048005
TI  - Jazz and the art of conversation.

PMID- 20048006
TI  - Psychological debriefing in schools.

PMID- 20048007
TI  - Why collect individual-level vaccination data?

PMID- 20048008
TI  - Holy fire in an HIV-positive man: a case of 21st-century ergotism.

PMID- 20048010
TI  - White coat revisited.

PMID- 20048009
TI  - Proliferation of prenatal ultrasonography.
AB  - BACKGROUND: The extent to which temporal increases in the use of prenatal
      ultrasonography reflect changes in maternal risk is unknown. In this population
      based study, we examined the use of prenatal ultrasonography from 1996 to 2006 in
      Ontario. METHODS: With fiscal year 1996/97 as the baseline, we evaluated the
      relative risk (RR) and 95% confidence interval (CI) for the change in rates of
      ultrasonography for each subsequent year. The RR was adjusted for maternal age,
      income, rural residence, maternal comorbidities, receipt of genetics consultation
      or amniocentesis--all in the index pregnancy--and history of complications in a
      prior pregnancy. RESULTS: The study sample consisted of 1 399 389 singleton
      deliveries. The rate of prenatal ultrasonography increased from 2055 per 1000
      pregnancies in 1996 to 3264 per 1000 in 2006 (adjusted RR 1.55, 95% CI 1.54
      1.55). The rate increased among both women with low-risk pregnancies (adjusted RR
      1.54, 95% CI 1.53-1.55) and those with high-risk pregnancies (adjusted RR 1.55,
      95% CI 1.54-1.57). The proportion of pregnancies with at least four ultrasound
      examinations in the second or third trimesters rose from 6.4% in 1996 to 18.7% in
      2006 (adjusted RR 2.68, 95% CI 2.61-2.74). Paradoxically, this increase was more
      pronounced among low-risk pregnancies (adjusted RR 2.92, 95% CI 2.83-3.01) than
      among high-risk pregnancies (adjusted RR 2.25, 95% CI 2.16-2.35). INTERPRETATION:
      Substantial increases in the use of prenatal ultrasonography over the past decade
      do not appear to reflect changes in maternal risk. Nearly one in five women now
      undergo four or more ultrasound examinations during the second and third
      trimesters. Efforts to promote more appropriate use of prenatal ultrasonography
      for singleton pregnancies appear warranted.

PMID- 20048012
TI  - Anatomic anomaly in renal blunt trauma.

PMID- 20048013
TI  - Selecting educational interventions for knowledge translation.

PMID- 20048014
TI  - Concerns raised about Ontario's new regime for bariatric surgery.

PMID- 20048015
TI  - Tamiflu still prudent for pandemic influenza, PHAC maintains.

PMID- 20048016
TI  - Nursing degree "opens doors beyond bags, beds and bedpans".

PMID- 20048017
TI  - Raise taxes on high-alcohol products, British Columbia urged.

PMID- 20048018
TI  - The ETS oncogene family transcription factor FEV identifies serotonin-producing
      cells in normal and neoplastic small intestine.
AB  - Neuroendocrine (NE) or carcinoid tumors of the small intestine (SI) frequently
      metastasize and produce the hormone serotonin, causing significant morbidity and
      mortality. A member of the ETS oncogene family of transcription factors, Fev,
      acts with the homeodomain transcription factor Nkx2.2 in the development of
      serotonin neurons in mice. In this study, we investigated the role of Fev in
      normal and neoplastic SI. In NE tumors (NETs) of the SI, serotonin stimulates
      tumor growth and causes debilitating symptoms, such as diarrhea, flushing,
      wheezing, and right-sided valvular heart disease (i.e. carcinoid syndrome).
      Compared with those in the matched normal human SI, FEV expression levels were
      significantly elevated in primary NETs (20-fold, P<0.0001), lymph node metastases
      (35-fold, P=0.004), and NET liver metastases (22-fold, P<0.0001) resected from
      patients with serotonin excess. Fev is expressed in the wild type but not in
      Nkx2.2 (-/-) mouse SI, in which cells producing serotonin are absent. Using
      recombination-based cell lineage tracing, we found that FEV-positive cells give
      rise to serotonin-producing cells in the SI. In Fev (-/-) mouse SI, we observed
      no difference in the number of cells producing serotonin or other hormones. We
      conclude that FEV expression identifies serotonin-producing cells in normal and
      neoplastic SI and is a novel target for diagnosis of patients with NETs of the
      SI.

PMID- 20048019
TI  - Suppression of the P50 evoked response and neuregulin 1-induced AKT
      phosphorylation in first-episode schizophrenia.
AB  - OBJECTIVE: Diminished suppression of the P50 auditory evoked potential is a
      widely used sensory gating phenotype in the molecular genetic studies of
      schizophrenia. The aim of this study was to explore the relationship between this
      phenotype and neuregulin 1-related intracellular signaling processes. METHOD: The
      P50 evoked potential was recorded in 30 first-episode, never-medicated patients
      with schizophrenia and in 30 healthy comparison volunteers. Neuregulin 1-induced
      activation of the phosphoinositide 3'-kinase (PI3K)/protein kinase B
      (AKT)/glycogen synthase kinase-3beta system was characterized by the measurement
      of the phosphorylated AKT to total AKT ratio in peripheral B lymphoblasts.
      RESULTS: Relative to comparison subjects, patients with first-episode
      schizophrenia displayed diminished P50 suppression and decreased neuregulin 1
      induced AKT phosphorylation. There was a significant relationship between P50
      suppression and AKT phosphorylation. CONCLUSION: Decreased neuregulin 1-induced
      activation of the PI3K/AKT system is associated with impaired sensory gating in
      first-episode schizophrenia.

PMID- 20048020
TI  - Association of Western and traditional diets with depression and anxiety in
      women.
AB  - OBJECTIVE: Key biological factors that influence the development of depression
      are modified by diet. This study examined the extent to which the high-prevalence
      mental disorders are related to habitual diet in 1,046 women ages 20-93 years
      randomly selected from the population. METHOD: A diet quality score was derived
      from answers to a food frequency questionnaire, and a factor analysis identified
      habitual dietary patterns. The 12-item General Health Questionnaire (GHQ-12) was
      used to measure psychological symptoms, and a structured clinical interview was
      used to assess current depressive and anxiety disorders. RESULTS: After
      adjustments for age, socioeconomic status, education, and health behaviors, a
      "traditional" dietary pattern characterized by vegetables, fruit, meat, fish, and
      whole grains was associated with lower odds for major depression or dysthymia and
      for anxiety disorders. A "western" diet of processed or fried foods, refined
      grains, sugary products, and beer was associated with a higher GHQ-12 score.
      There was also an inverse association between diet quality score and GHQ-12 score
      that was not confounded by age, socioeconomic status, education, or other health
      behaviors. CONCLUSIONS: These results demonstrate an association between habitual
      diet quality and the high-prevalence mental disorders, although reverse causality
      and confounding cannot be ruled out as explanations. Further prospective studies
      are warranted.

PMID- 20048021
TI  - Static and dynamic cognitive deficits in childhood preceding adult schizophrenia:
      a 30-year study.
AB  - OBJECTIVE: Premorbid cognitive deficits in schizophrenia are well documented and
      have been interpreted as supporting a neurodevelopmental etiological model. The
      authors investigated the following three unresolved questions about premorbid
      cognitive deficits: What is their developmental course? Do all premorbid
      cognitive deficits follow the same course? Are premorbid cognitive deficits
      specific to schizophrenia or shared by other psychiatric disorders? METHOD:
      Participants were members of a representative cohort of 1,037 males and females
      born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent
      follow-up evaluations at specific intervals from age 3 to 32 years, with a 96%
      retention rate. Cognitive development was analyzed and compared in children who
      later developed schizophrenia or recurrent depression as well as in healthy
      comparison subjects. RESULTS: Children who developed adult schizophrenia
      exhibited developmental deficits (i.e., static cognitive impairments that emerge
      early and remain stable) on tests indexing verbal and visual knowledge
      acquisition, reasoning, and conceptualization. In addition, these children
      exhibited developmental lags (i.e., growth that is slower relative to healthy
      comparison subjects) on tests indexing processing speed, attention, visual
      spatial problem solving ability, and working memory. These two premorbid
      cognitive patterns were not observed in children who later developed recurrent
      depression. CONCLUSIONS: These findings suggest that the origins of schizophrenia
      include two interrelated developmental processes evident from childhood to early
      adolescence (ages 7-13 years). Children who will grow up to develop adult
      schizophrenia enter primary school struggling with verbal reasoning and lag
      further behind their peers in working memory, attention, and processing speed as
      they get older.

PMID- 20048022
TI  - The psychiatric sequelae of traumatic injury.
AB  - OBJECTIVE: Traumatic injury affects millions of people each year. There is little
      understanding of the extent of psychiatric illness that develops after traumatic
      injury or of the impact of mild traumatic brain injury (TBI) on psychiatric
      illness. The authors sought to determine the range of new psychiatric disorders
      occurring after traumatic injury and the influence of mild TBI on psychiatric
      status. METHOD: In this prospective cohort study, patients were drawn from recent
      admissions to four major trauma hospitals across Australia. A total of 1,084
      traumatically injured patients were initially assessed during hospital admission
      and followed up 3 months (N=932, 86%) and 12 months (N=817, 75%) after injury.
      Lifetime psychiatric diagnoses were assessed in hospital. The prevalence of
      psychiatric disorders, levels of quality of life, and mental health service use
      were assessed at the follow-ups. The main outcome measures were 3- and 12-month
      prevalence of axis I psychiatric disorders, levels of quality of life, and mental
      health service use and lifetime axis I psychiatric disorders. RESULTS: Twelve
      months after injury, 31% of patients reported a psychiatric disorder, and 22%
      developed a psychiatric disorder that they had never experienced before. The most
      common new psychiatric disorders were depression (9%), generalized anxiety
      disorder (9%), posttraumatic stress disorder (6%), and agoraphobia (6%). Patients
      were more likely to develop posttraumatic stress disorder (odds ratio=1.92, 95%
      CI=1.08-3.40), panic disorder (odds ratio=2.01, 95% CI=1.03-4.14), social phobia
      (odds ratio=2.07, 95% CI=1.03-4.16), and agoraphobia (odds ratio=1.94, 95%
      CI=1.11-3.39) if they had sustained a mild TBI. Functional impairment, rather
      than mild TBI, was associated with psychiatric illness. CONCLUSIONS: A
      significant range of psychiatric disorders occur after traumatic injury. The
      identification and treatment of a range of psychiatric disorders are important
      for optimal adaptation after traumatic injury.

PMID- 20048023
TI  - Evidence, limes, and cement.

PMID- 20048024
TI  - Vertebroplasty, cognitive dissonance, and evidence-based medicine: what do we do
      when the 'evidence' says we are wrong?

PMID- 20048025
TI  - Consternation and questions about two vertebroplasty trials.

PMID- 20048026
TI  - Acetaminophen: old drug, new warnings.
AB  - The US Food and Drug Administration (FDA), concerned about the incidence of acute
      liver failure due to acetaminophen (Tylenol) overdose, has mandated new labeling
      on acetaminophen packaging. It is also considering (but has not enacted) reducing
      the maximum daily dose from 4 g (possibly to 3,250 mg), banning acetaminophen
      narcotic combination products, and changing the current maximum single dose of 1
      g to prescription status, making 650 mg the highest recommended nonprescription
      dose. We review the epidemiology, toxicology, and management of acetaminophen
      overdose and steps the FDA and physicians can take to prevent it.

PMID- 20048027
TI  - Lesions on the hands, high aminotransferase levels.

PMID- 20048028
TI  - Myelodysplastic syndromes: a practical approach to diagnosis and treatment.
AB  - The myelodysplastic syndromes (MDS) are clonal bone marrow disorders that lead to
      underproduction of normal blood cells. The consequent cytopenias result in
      infections and bleeding complications. MDS transform to acute myeloid leukemia in
      one-third of patients. The number of diagnoses has exploded in the past decade as
      a result of increased recognition and understanding of the disease and the aging
      of the population. New therapies can extend life. MDS are now considered the most
      common form of leukemia, and in some cases deserve immediate intervention. This
      review describes common presentations of MDS, optimal diagnostic approaches, and
      therapies for lower-and higher-risk disease.

PMID- 20048029
TI  - Abdominal pain in a 20-year-old woman.

PMID- 20048030
TI  - Food allergy and eosinophilic esophagitis: learning what to avoid.
AB  - Food allergies have increased in prevalence significantly in the past decade and
      so, apparently, has eosinophilic esophagitis. Although the cause of eosinophilic
      esophagitis is unknown, allergic responses including food allergies have been
      implicated. This article reviews both conditions, focusing on how to detect and
      manage them.

PMID- 20048031
TI  - Q: Should we routinely screen for hypercapnia in sleep apnea patients before
      elective noncardiac surgery?

PMID- 20048032
TI  - Chest pain in children and adolescents.

PMID- 20048033
TI  - Expanding our horizons.

PMID- 20048034
TI  - Heart failure in infants and children.

PMID- 20048035
TI  - Pediatric tuberculosis.

PMID- 20048036
TI  - Research and statistics: validity hierarchy for study design and study type.

PMID- 20048037
TI  - Pediatrics in the community: "keep smiling!" the Florida fluoride project.

PMID- 20048038
TI  - Index of suspicion.

PMID- 20048039
TI  - Vaccines in immunocompromised patients.

PMID- 20048040
TI  - The gifted child.

PMID- 20048041
TI  - Microscopic detection of viable Staphylococcus epidermidis in peri-implant tissue
      in experimental biomaterial-associated infection, identified by bromodeoxyuridine
      incorporation.
AB  - Infection of biomedical devices is characterized by biofilm formation and
      colonization of surrounding tissue by the causative pathogens. To investigate
      whether bacteria detected microscopically in tissue surrounding infected devices
      were viable, we used bromodeoxyuridine (BrdU), a nucleotide analogue that is
      incorporated into bacterial DNA and can be detected with antibodies. Infected
      human tissue was obtained postmortem from patients with intravascular devices,
      and mouse biopsy specimens were obtained from mice with experimental biomaterial
      infection. In vitro experiments showed that Staphylococcus epidermidis
      incorporated BrdU, as judged from staining of the bacteria with anti-BrdU
      antibodies. After incubation of bacteria with BrdU and subsequent staining of
      microscopic sections with anti-BrdU antibodies, bacteria could be clearly
      visualized in the tissue surrounding intravascular devices of deceased patients.
      With this staining technique, relapse of infection could be visualized in mice
      challenged with a low dose of S. epidermidis and treated with dexamethasone
      between 14 and 21 days after challenge to suppress immunity. This confirms and
      extends our previous findings that pericatheter tissue is a reservoir for
      bacteria in biomaterial-associated infection. The pathogenesis of the infection
      and temporo-spatial distribution of viable, dividing bacteria can now be studied
      at the microscopic level by immunolabeling with BrdU and BrdU antibodies.

PMID- 20048042
TI  - Pseudomonas aeruginosa alginate promotes Burkholderia cenocepacia persistence in
      cystic fibrosis transmembrane conductance regulator knockout mice.
AB  - Pseudomonas aeruginosa, a major respiratory pathogen in cystic fibrosis (CF)
      patients, facilitates infection by other opportunistic pathogens. Burkholderia
      cenocepacia, which normally infects adolescent patients, encounters alginate
      elaborated by mucoid P. aeruginosa. To determine whether P. aeruginosa alginate
      facilitates B. cenocepacia infection in mice, cystic fibrosis transmembrane
      conductance regulator knockout mice were infected with B. cenocepacia strain BC7
      suspended in either phosphate-buffered saline (BC7/PBS) or P. aeruginosa alginate
      (BC7/alginate), and the pulmonary bacterial load and inflammation were monitored.
      Mice infected with BC7/PBS cleared all of the bacteria within 3 days, and
      inflammation was resolved by day 5. In contrast, mice infected with BC7/alginate
      showed persistence of bacteria and increased cytokine levels for up to 7 days.
      Histological examination of the lungs indicated that there was moderate to severe
      inflammation and pneumonic consolidation in isolated areas at 5 and 7 days
      postinfection in the BC7/alginate group. Further, alginate decreased phagocytosis
      of B. cenocepacia by professional phagocytes both in vivo and in vitro. P.
      aeruginosa alginate also reduced the proinflammatory responses of CF airway
      epithelial cells and alveolar macrophages to B. cenocepacia infection. The
      observed effects are specific to P. aeruginosa alginate, because enzymatically
      degraded alginate or other polyuronic acids did not facilitate bacterial
      persistence. These observations suggest that P. aeruginosa alginate may
      facilitate B. cenocepacia infection by interfering with host innate defense
      mechanisms.

PMID- 20048043
TI  - Neisseria gonorrhoeae survival during primary human cervical epithelial cell
      infection requires nitric oxide and is augmented by progesterone.
AB  - Neisseria gonorrhoeae is an obligate human pathogen that causes gonorrhea. We
      have shown previously that complement receptor 3 and Akt kinase play important
      roles in mediating cervical infection. At present, there are limited data to
      indicate how hormonally induced changes to the mucosal epithelia of the female
      genital tract mediate the course of gonococcal disease. Hence, I have expanded
      upon previous work to investigate the interaction of gonococci with primary human
      cervical epithelial (pex) cells under the variable estrogen and progesterone
      concentrations likely to be encountered in vivo throughout the female menstrual
      cycle. My data indicated that the ability of gonococci to survive and to
      replicate within pex cells was increased under progesterone-predominant
      conditions. Using bacterial survival, immunological, and kinase assays, I show
      that progesterone functioned in an additive manner with gonococcal phospholipase
      D to augment Akt kinase activity. This, in turn, resulted in a parallel increase
      in nitric oxide synthase expression. Nitric oxide production by pex cells was
      dependent upon Akt activity and was increased under progesterone-predominant
      conditions. Whereas both inducible and endothelial nitric oxide synthase
      contributed to nitric oxide production, only inducible nitric oxide synthase
      activity promoted gonococcal survival within pex cells. Collectively, these data
      provide the first clues as to how steroid hormones potentially modulate the
      course of gonococcal disease in women. In addition, these data demonstrate that
      host-derived nitric oxide likely is not protective against gonococci, in vivo;
      rather, nitric oxide may be required to sustain cervical bacterial disease.

PMID- 20048044
TI  - Cryptococcus neoformans variants generated by phenotypic switching differ in
      virulence through effects on macrophage activation.
AB  - Macrophages have a central role in the pathogenesis of cryptococcosis since they
      are an important line of defense, serve as a site for fungal replication, and
      also can contribute to tissue damage. The objective of this study was to
      investigate the interaction of macrophages with cells from smooth-colony variants
      (SM) and mucoid-colony variants (MC) arising from phenotypic switching of
      Cryptococcus neoformans. Alveolar macrophages (AMs) isolated from SM- and MC
      infected mice exhibited differences in gene and surface expression of PD-L1, PD
      L2, and major histocompatibility class II (MHC-II). PD-L1 and PD-L2 are the
      ligands for PD1 and are differentially regulated in Th1- and Th2-type cells. In
      addition, macrophage activation in SM- and MC-infected mice was characterized as
      alternatively activated. Flow cytometric and cytokine analysis demonstrated that
      MC infection was associated with the emergence of Th17 cells and higher levels of
      interleukin-17 (IL-17) in lung tissue, which were reduced by AM depletion. In
      conclusion, our results indicate that macrophages play a significant role in
      maintaining damage-promoting inflammation in the lung during MC infection, which
      ultimately results in death.

PMID- 20048045
TI  - Suppression of Plasmodium cynomolgi in rhesus macaques by coinfection with
      Babesia microti.
AB  - Both Plasmodium and Babesia species are intraerythrocytic protozoans that infect
      a wide range of hosts, including humans, and they elicit similar inflammatory
      responses and clinical manifestations that differ markedly in severity. We
      recently reported that a rhesus macaque that was chronically infected with
      Babesia microti was able to control infection with Plasmodium cynomolgi (a
      parasite of macaques with characteristics very similar to those of Plasmodium
      vivax) better than naive monkeys. To confirm this and to investigate the
      underlying immunopathology, six naive rhesus monkeys were infected with B.
      microti. After 24 days, four of these monkeys and four naive rhesus monkeys were
      challenged with P. cynomolgi blood-stage parasites. B. microti persisted at low
      levels in all monkeys, and the clinical parameters were comparable to those of
      noninfected controls. There was a significant decrease in P. cynomolgi
      parasitemia in animals coinfected with B. microti compared to the parasitemia in
      animals infected with P. cynomolgi alone. This decrease in P. cynomolgi
      parasitemia correlated with increases in the levels of proinflammatory monocytes
      at the time of P. cynomolgi infection and with higher C-reactive protein (CRP)
      serum levels 1 week after malaria infection. Therefore, we conclude that ongoing
      infection with B. microti parasites leads to suppression of malaria infection.

PMID- 20048046
TI  - Intranasal vaccinations with the trans-sialidase antigen plus CpG Adjuvant induce
      mucosal immunity protective against conjunctival Trypanosoma cruzi challenges.
AB  - Trypanosoma cruzi is an intracellular protozoan parasite capable of infecting
      through mucosal surfaces. Our laboratory has previously elucidated the anatomical
      routes of infection after both conjunctival and gastric challenge in mice. We
      have shown that chronically infected mice develop strong immune responses capable
      of protecting against subsequent rechallenge with virulent parasites through
      gastric, conjunctival, and systemic routes of infection. We have also shown that
      intranasal immunizations with the unique T. cruzi trans-sialidase (TS) antigen
      protect against gastric and systemic T. cruzi challenge. In the current work we
      have investigated the ability of purified TS adjuvanted with CpG-containing
      oligonucleotides to induce immunity against conjunctival T. cruzi challenge. We
      confirm that intranasal vaccinations with TS plus CpG induce TS-specific T-cell
      and secretory IgA responses. TS-specific secretory IgA was detectable in the
      tears of vaccinated mice, the initial body fluid that contacts the parasite
      during infectious conjunctival exposures. We further show that intranasal
      vaccinations with TS plus CpG protect against conjunctival T. cruzi challenge,
      limiting local parasite replication at the site of mucosal invasion and systemic
      parasite dissemination. We also provide the first direct evidence that mucosal
      antibodies induced by intranasal TS vaccination can inhibit parasite invasion.

PMID- 20048047
TI  - Pore formation triggered by Legionella spp. is an Nlrc4 inflammasome-dependent
      host cell response that precedes pyroptosis.
AB  - Legionella pneumophila, the etiological agent of Legionnaires disease, is known
      to trigger pore formation in bone marrow-derived macrophages (BMMs) by mechanisms
      dependent on the type IVB secretion system known as Dot/Icm. Here, we used
      several mutants of L. pneumophila in combination with knockout mice to assess the
      host and bacterial factors involved in pore formation in BMMs. We found that
      regardless of Dot/Icm activity, pore formation does not occur in BMMs deficient
      in caspase-1 and Nlrc4/Ipaf. Pore formation was temporally associated with
      interleukin-1beta secretion and preceded host cell lysis and pyroptosis. Pore
      forming ability was dependent on bacterial Dot/Icm but independent of several
      effector proteins, multiplication, and de novo protein synthesis. Flagellin,
      which is known to trigger the Nlrc4 inflammasome, was required for pore formation
      as flaA mutant bacteria failed to induce cell permeabilization. Accordingly,
      transfection of purified flagellin was sufficient to trigger pore formation
      independent of infection. By using 11 different Legionella species, we found
      robust pore formation in response to L. micdadei, L. bozemanii, L. gratiana, L.
      jordanis, and L. rubrilucens, and this trait correlated with flagellin expression
      by these species. Together, the results suggest that pore formation is neither L.
      pneumophila specific nor the result of membrane damage induced by Dot/Icm
      activity; instead, it is a highly coordinated host cell response dependent on
      host Nlrc4 and caspase-1 and on bacterial flagellin and type IV secretion system.

PMID- 20048048
TI  - Population polymorphism of nuclear mitochondrial DNA insertions reveals
      widespread diploidy associated with loss of heterozygosity in Debaryomyces
      hansenii.
AB  - Debaryomyces hansenii, a yeast that participates in the elaboration of foodstuff,
      displays important genetic diversity. Our recent phylogenetic classification of
      this species led to the subdivision of the species into three distinct clades. D.
      hansenii harbors the highest number of nuclear mitochondrial DNA (NUMT)
      insertions known so far for hemiascomycetous yeasts. Here we assessed the
      intraspecific variability of the NUMTs in this species by testing their
      presence/absence first in 28 strains, with 21 loci previously detected in the
      completely sequenced strain CBS 767(T), and second in a larger panel of 77
      strains, with 8 most informative loci. We were able for the first time to
      structure populations in D. hansenii, although we observed little NUMT insertion
      variability within the clades. We determined the chronology of the NUMT
      insertions, which turned out to correlate with the previously defined taxonomy
      and provided additional evidence that colonization of nuclear genomes by
      mitochondrial DNA is a dynamic process in yeast. In combination with flow
      cytometry experiments, the NUMT analysis revealed the existence of both haploid
      and diploid strains, the latter being heterozygous and resulting from at least
      four crosses among strains from the various clades. As in the diploid pathogen
      Candida albicans, to which D. hansenii is phylogenetically related, we observed a
      differential loss of heterozygosity in the diploid strains, which can explain
      some of the large genetic diversity found in D. hansenii over the years.

PMID- 20048050
TI  - Bayesian quantitative trait locus mapping using inferred haplotypes.
AB  - We describe a fast hierarchical Bayesian method for mapping quantitative trait
      loci by haplotype-based association, applicable when haplotypes are not observed
      directly but are inferred from multiple marker genotypes. The method avoids the
      use of a Monte Carlo Markov chain by employing priors for which the likelihood
      factorizes completely. It is parameterized by a single hyperparameter, the
      fraction of variance explained by the quantitative trait locus, compared to the
      frequentist fixed-effects model, which requires a parameter for the phenotypic
      effect of each combination of haplotypes; nevertheless it still provides
      estimates of haplotype effects. We use simulation to show that the method matches
      the power of the frequentist regression model and, when the haplotypes are
      inferred, exceeds it for small QTL effect sizes. The Bayesian estimates of the
      haplotype effects are more accurate than the frequentist estimates, for both
      known and inferred haplotypes, which indicates that this advantage is independent
      of the effect of uncertainty in haplotype inference and will hold in comparison
      with frequentist methods in general. We apply the method to data from a panel of
      recombinant inbred lines of Arabidopsis thaliana, descended from 19 inbred
      founders.

PMID- 20048049
TI  - Activation of a poised RNAPII-dependent promoter requires both SAGA and mediator.
AB  - A growing number of promoters have key components of the transcription machinery,
      such as TATA-binding protein (TBP) and RNA polymerase II (RNAPII), present at the
      promoter prior to activation of transcription. Thus, while transcriptional output
      undergoes a dramatic increase between uninduced and induced conditions, occupancy
      of a large portion of the transcription machinery does not. As such, activation
      of these poised promoters depends on rate-limiting steps after recruitment of TBP
      and RNAPII for regulated expression. Little is known about the transcription
      components required in these latter steps of transcription in vivo. To identify
      components with critical roles in transcription after recruitment of TBP in
      Saccharomyces cerevisiae, we screened for loss of gene expression activity from
      promoter-tethered TBP in >100 mutant strains deleted for a transcription-related
      gene. The assay revealed a dramatic enrichment for strains containing deletions
      in genes encoding subunits of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex
      and Mediator. Analysis of an authentic postrecruitment-regulated gene (CYC1)
      reveals that SAGA occupies the promoter under both uninduced and induced
      conditions. In contrast, Mediator is recruited only after transfer to inducing
      conditions and correlates with activation of the preloaded polymerase at CYC1.
      These studies indicate the critical functions of SAGA and Mediator in the
      mechanism of activation of genes with rate-limiting steps after recruitment of
      TBP.

PMID- 20048051
TI  - Simple Y-autosomal incompatibilities cause hybrid male sterility in reciprocal
      crosses between Drosophila virilis and D. americana.
AB  - Postzygotic reproductive isolation evolves when hybrid incompatibilities
      accumulate between diverging populations. Here, I examine the genetic basis of
      hybrid male sterility between two species of Drosophila, Drosophila virilis and
      D. americana. From these analyses, I reach several conclusions. First, neither
      species carries any autosomal dominant hybrid male sterility alleles: reciprocal
      F(1) hybrid males are perfectly fertile. Second, later generation (backcross and
      F(2)) hybrid male sterility between D. virilis and D. americana is not polygenic.
      In fact, I identified only three genetically independent incompatibilities that
      cause hybrid male sterility. Remarkably, each of these incompatibilities involves
      the Y chromosome. In one direction of the cross, the D. americana Y is
      incompatible with recessive D. virilis alleles at loci on chromosomes 2 and 5. In
      the other direction, the D. virilis Y chromosome causes hybrid male sterility in
      combination with recessive D. americana alleles at a single QTL on chromosome 5.
      Finally, in contrast with findings from other Drosophila species pairs, the X
      chromosome has only a modest effect on hybrid male sterility between D. virilis
      and D. americana.

PMID- 20048052
TI  - Sterile alpha motif domain-mediated self-association plays an essential role in
      modulating the activity of the Drosophila ETS family transcriptional repressor
      Yan.
AB  - The ETS family transcriptional repressor Yan is an important downstream target
      and effector of the receptor tyrosine kinase (RTK) signaling pathway in
      Drosophila melanogaster. Structural and biochemical studies have shown that the N
      terminal sterile alpha motif (SAM) of Yan is able to self associate to form a
      helical polymeric structure in vitro, although the extent and functional
      significance of self-association of full-length Yan remain unclear. In this
      study, we demonstrated that full-length Yan self associates via its SAM domain to
      form higher-order complexes in living cells. Introduction of SAM domain missense
      mutations that restrict Yan to a monomeric state reduces Yan's transcriptional
      repression activity and impairs its function during embryonic and retinal
      development. Coexpression of combinations of SAM domain mutations that permit the
      formation of Yan dimers, but not higher-order oligomers, increases activity
      relative to that of monomeric Yan, but not to the level obtained with wild-type
      Yan. Mechanistically, self-association directly promotes transcriptional
      repression of target genes independent of its role in limiting mitogen-activated
      protein kinase (MAPK)-mediated phosphorylation and nuclear export of Yan. Thus,
      we propose that the formation of higher-order Yan oligomers contributes to proper
      repression of target gene expression and RTK signaling output in developing
      tissues.

PMID- 20048053
TI  - Asf1 can promote trimethylation of H3 K36 by Set2.
AB  - Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble
      nucleosomes and promote histone acetylation. Set2 is an H3 K36 methyltransferase.
      The functions of these proteins intersect in the context of transcription
      elongation by RNA polymerase II: both contribute to the establishment of
      repressive chromatin structures that inhibit spurious intragenic transcription.
      Here we characterize further interactions between budding yeast (Saccharomyces
      cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4
      posttranslational modification, coding region cross-linking of Asf1 and Set2, and
      cooccurrence of Asf1 and Set2 in protein complexes. We find that at some genes
      Asf1 and Set2 control chromatin metabolism as components of separate pathways.
      However, the existence of a low-abundance complex containing both proteins
      suggests that Asf1 and Set2 can more directly collaborate in chromatin
      regulation. Consistent with this possibility, we show that Asf1 stimulates Set2
      occupancy of the coding region of a highly transcribed gene by a mechanism that
      depends on Asf1 binding to H3/H4. This function of Asf1 promotes the switch from
      di- to trimethylation of H3 K36 at that gene. These results support the view that
      Set2 function in chromatin metabolism can intimately involve histone chaperone
      Asf1.

PMID- 20048054
TI  - FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen
      receptor signaling in prostate cancer cells.
AB  - Prostate cancer progression to the androgen-independent (AI) state involves
      acquisition of pathways that allow tumor growth under low-androgen conditions. We
      hypothesized that expression of molecular chaperones that modulate androgen
      binding to AR might be altered in prostate cancer and contribute to progression
      to the AI state. Here, we report that the Hsp90 cochaperone FKBP51 is upregulated
      in LAPC-4 AI tumors grown in castrated mice and describe a molecular mechanism by
      which FKBP51 regulates AR activity. Using recombinant proteins, we show that
      FKBP51 stimulates recruitment of the cochaperone p23 to the ATP-bound form of
      Hsp90, forming an FKBP51-Hsp90-p23 superchaperone complex. In cells, FKBP51
      expression promotes superchaperone complex association with AR and increases the
      number of AR molecules that undergo androgen binding. FKBP51 stimulates androgen
      dependent transcription and cell growth, and FKBP51 is part of a positive
      feedback loop that is regulated by AR and androgen. Finally, depleting FKBP51
      levels by short hairpin RNA reduces the transcript levels of genes regulated by
      AR and androgen. Because the superchaperone complex plays a critical role in
      determining the ligand-binding competence and transcription function of AR, it
      provides an attractive target for inhibiting AR activity in prostate cancer
      cells.

PMID- 20048055
TI  - Paralytic shellfish poisoning toxin-producing cyanobacterium Aphanizomenon
      gracile in northeast Germany.
AB  - Neurotoxic paralytic shellfish poisoning (PSP) toxins, anatoxin-a (ATX), and
      hepatotoxic cylindrospermopsin (CYN) have been detected in several lakes in
      northeast Germany during the last 2 decades. They are produced worldwide by
      members of the nostocalean genera Anabaena, Cylindrospermopsis, and
      Aphanizomenon. Although no additional sources of PSP toxins and ATX have been
      identified in German water bodies to date, the observed CYN concentrations cannot
      be produced solely by Aphanizomenon flos-aquae, the only known CYN producer in
      Germany. Therefore, we attempted to identify PSP toxin, ATX, and CYN producers by
      isolating and characterizing 92 Anabaena, Aphanizomenon, and Anabaenopsis strains
      from five lakes in northeast Germany. In a polyphasic approach, all strains were
      morphologically and phylogenetically classified and then tested for PSP toxins,
      ATX, and CYN by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and
      enzyme-linked immunosorbent assay (ELISA) and screened for the presence of PSP
      toxin- and CYN-encoding gene fragments. As demonstrated by ELISA and LC-MS, 14
      Aphanizomenon gracile strains from Lakes Melang and Scharmutzel produced four PSP
      toxin variants (gonyautoxin 5 [GTX5], decarbamoylsaxitoxin [dcSTX], saxitoxin
      [STX], and neosaxitoxin [NEO]). GTX5 was the most prevalent PSP toxin variant
      among the seven strains from Lake Scharmutzel, and NEO was the most prevalent
      among the seven strains from Lake Melang. The sxtA gene, which is part of the
      saxitoxin gene cluster, was found in the 14 PSP toxin-producing A. gracile
      strains and in 11 non-PSP toxin-producing Aphanizomenon issatschenkoi, A. flos
      aquae, Anabaena planktonica, and Anabaenopsis elenkinii strains. ATX and CYN were
      not detected in any of the isolated strains. This study is the first confirming
      the role of A. gracile as a PSP toxin producer in German water bodies.

PMID- 20048056
TI  - GacA-controlled activation of promoters for small RNA genes in Pseudomonas
      fluorescens.
AB  - The Gac/Rsm signal transduction pathway positively regulates secondary
      metabolism, production of extracellular enzymes, and biocontrol properties of
      Pseudomonas fluorescens CHA0 via the expression of three noncoding small RNAs,
      termed RsmX, RsmY, and RsmZ. The architecture and function of the rsmY and rsmZ
      promoters were studied in vivo. A conserved palindromic upstream activating
      sequence (UAS) was found to be necessary but not sufficient for rsmY and rsmZ
      expression and for activation by the response regulator GacA. A poorly conserved
      linker region located between the UAS and the -10 promoter sequence was also
      essential for GacA-dependent rsmY and rsmZ expression, suggesting a need for
      auxiliary transcription factors. One such factor involved in the activation of
      the rsmZ promoter was identified as the PsrA protein, previously recognized as an
      activator of the rpoS gene and a repressor of fatty acid degradation.
      Furthermore, the integration host factor (IHF) protein was found to bind with
      high affinity to the rsmZ promoter region in vitro, suggesting that DNA bending
      contributes to the regulated expression of rsmZ. In an rsmXYZ triple mutant, the
      expression of rsmY and rsmZ was elevated above that found in the wild type. This
      negative feedback loop appears to involve the translational regulators RsmA and
      RsmE, whose activity is antagonized by RsmXYZ, and several hypothetical DNA
      binding proteins. This highly complex network controls the expression of the
      three small RNAs in response to cell physiology and cell population densities.

PMID- 20048057
TI  - Influence of fatty acid precursors, including food preservatives, on the growth
      and fatty acid composition of Listeria monocytogenes at 37 and 10degreesC.
AB  - Listeria monocytogenes is a food-borne pathogen that grows at refrigeration
      temperatures and increases its content of anteiso-C(15:0) fatty acid, which is
      believed to be a homeoviscous adaptation to ensure membrane fluidity, at these
      temperatures. As a possible novel approach for control of the growth of the
      organism, the influences of various fatty acid precursors, including branched
      chain amino acids and branched- and straight-chain carboxylic acids, some of
      which are also well-established food preservatives, on the growth and fatty acid
      composition of the organism at 37 degrees C and 10 degrees C were studied in
      order to investigate whether the organism could be made to synthesize fatty acids
      that would result in impaired growth at low temperatures. The results indicate
      that the fatty acid composition of L. monocytogenes could be modulated by the
      feeding of branched-chain amino acid, C(4), C(5), and C(6) branched-chain
      carboxylic acid, and C(3) and C(4) straight-chain carboxylic acid fatty acid
      precursors, but the growth-inhibitory effects of several preservatives were
      independent of effects on fatty acid composition, which were minor in the case of
      preservatives metabolized via acetyl coenzyme A. The ability of a precursor to
      modify fatty acid composition was probably a reflection of the substrate
      specificities of the first enzyme, FabH, in the condensation of primers of fatty
      acid biosynthesis with malonyl acyl carrier protein.

PMID- 20048058
TI  - Isolation and characterization of bacteria resistant to metallic copper surfaces.
AB  - Metallic copper alloys have recently attracted attention as a new antimicrobial
      weapon for areas where surface hygiene is paramount. Currently it is not
      understood on a molecular level how metallic copper kills microbes, but previous
      studies have demonstrated that a wide variety of bacteria, including Escherichia
      coli, Staphylococcus aureus, and Clostridium difficile, are inactivated within
      minutes or a few hours of exposure. In this study, we show that bacteria isolated
      from copper alloy coins comprise strains that are especially resistant against
      the toxic properties exerted by dry metallic copper surfaces. The most resistant
      of 294 isolates were Gram-positive staphylococci and micrococci, Kocuria
      palustris, and Brachybacterium conglomeratum but also included the
      proteobacterial species Sphingomonas panni and Pseudomonas oleovorans. Cells of
      some of these bacterial strains survived on copper surfaces for 48 h or more.
      Remarkably, when these dry-surface-resistant strains were exposed to moist copper
      surfaces, resistance levels were close to those of control strains and MICs for
      copper ions were at or below control strain levels. This suggests that mechanisms
      conferring resistance against dry metallic copper surfaces in these newly
      isolated bacterial strains are different from well-characterized copper ion
      detoxification systems. Furthermore, staphylococci on coins did not exhibit
      increased levels of resistance to antibiotics, arguing against coselection with
      copper surface resistance traits.

PMID- 20048059
TI  - Automated quantification and sizing of unbranched filamentous cyanobacteria by
      model-based object-oriented image analysis.
AB  - Quantification and sizing of filamentous cyanobacteria in environmental samples
      or cultures are time-consuming and are often performed by using manual or
      semiautomated microscopic analysis. Automation of conventional image analysis is
      difficult because filaments may exhibit great variations in length and patchy
      autofluorescence. Moreover, individual filaments frequently cross each other in
      microscopic preparations, as deduced by modeling. This paper describes a novel
      approach based on object-oriented image analysis to simultaneously determine (i)
      filament number, (ii) individual filament lengths, and (iii) the cumulative
      filament length of unbranched cyanobacterial morphotypes in fluorescent
      microscope images in a fully automated high-throughput manner. Special emphasis
      was placed on correct detection of overlapping objects by image analysis and on
      appropriate coverage of filament length distribution by using large composite
      images. The method was validated with a data set for Planktothrix rubescens from
      field samples and was compared with manual filament tracing, the line intercept
      method, and the Utermohl counting approach. The computer program described allows
      batch processing of large images from any appropriate source and annotation of
      detected filaments. It requires no user interaction, is available free, and thus
      might be a useful tool for basic research and drinking water quality control.

PMID- 20048060
TI  - Source of nitrous oxide emissions during the cow manure composting process as
      revealed by isotopomer analysis of and amoA abundance in betaproteobacterial
      ammonia-oxidizing bacteria.
AB  - A molecular analysis of betaproteobacterial ammonia oxidizers and a N(2)O
      isotopomer analysis were conducted to study the sources of N(2)O emissions during
      the cow manure composting process. Much NO(2)(-)-N and NO(3)(-)-N and the
      Nitrosomonas europaea-like amoA gene were detected at the surface, especially at
      the top of the composting pile, suggesting that these ammonia-oxidizing bacteria
      (AOB) significantly contribute to the nitrification which occurs at the surface
      layer of compost piles. However, the (15)N site preference within the asymmetric
      N(2)O molecule (SP = delta(15)N(alpha) - delta(15)N(beta), where (15)N(alpha) and
      (15)N(beta) represent the (15)N/(14)N ratios at the center and end sites of the
      nitrogen atoms, respectively) indicated that the source of N(2)O emissions just
      after the compost was turned originated mainly from the denitrification process.
      Based on these results, the reduction of accumulated NO(2)(-)-N or NO(3)(-)-N
      after turning was identified as the main source of N(2)O emissions. The site
      preference and bulk delta(15)N results also indicate that the rate of N(2)O
      reduction was relatively low, and an increased value for the site preference
      indicates that the nitrification which occurred mainly in the surface layer of
      the pile partially contributed to N(2)O emissions between the turnings.

PMID- 20048061
TI  - Probing the molecular determinant for the catalytic efficiency of L-arabinose
      isomerase from Bacillus licheniformis.
AB  - Bacillus licheniformis l-arabinose isomerase (l-AI) is distinguished from other l
      AIs by its high degree of substrate specificity for l-arabinose and its high
      turnover rate. A systematic strategy that included a sequence alignment-based
      first screening of residues and a homology model-based second screening, followed
      by site-directed mutagenesis to alter individual screened residues, was used to
      study the molecular determinants for the catalytic efficiency of B. licheniformis
      l-AI. One conserved amino acid, Y333, in the substrate binding pocket of the wild
      type B. licheniformis l-AI was identified as an important residue affecting the
      catalytic efficiency of B. licheniformis l-AI. Further insights into the function
      of residue Y333 were obtained by replacing it with other aromatic, nonpolar
      hydrophobic amino acids or polar amino acids. Replacing Y333 with the aromatic
      amino acid Phe did not alter catalytic efficiency toward l-arabinose. In
      contrast, the activities of mutants containing a hydrophobic amino acid (Ala,
      Val, or Leu) at position 333 decreased as the size of the hydrophobic side chain
      of the amino acid decreased. However, mutants containing hydrophilic and charged
      amino acids, such as Asp, Glu, and Lys, showed almost no activity with l
      arabinose. These data and a molecular dynamics simulation suggest that Y333 is
      involved in the catalytic efficiency of B. licheniformis l-AI.

PMID- 20048062
TI  - Identification by suppression subtractive hybridization of Frankia genes induced
      under nitrogen-fixing conditions.
AB  - Frankia is an actinobacterium that fixes nitrogen under both symbiotic and free
      living conditions. We identified genes upregulated in free-living nitrogen-fixing
      cells by using suppression subtractive hybridization. They included genes with
      predicted functions related to nitrogen fixation, as well as with unknown
      function. Their upregulation was a novel finding in Frankia.

PMID- 20048063
TI  - Conserved symbiotic plasmid DNA sequences in the multireplicon pangenomic
      structure of Rhizobium etli.
AB  - Strains of the same bacterial species often show considerable genomic variation.
      To examine the extent of such variation in Rhizobium etli, the complete genome
      sequence of R. etli CIAT652 and the partial genomic sequences of six additional
      R. etli strains having different geographical origins were determined. The
      sequences were compared with each other and with the previously reported genome
      sequence of R. etli CFN42. DNA sequences common to all strains constituted the
      greater part of these genomes and were localized in both the chromosome and large
      plasmids. About 700 to 1,000 kb of DNA that did not match sequences of the
      complete genomes of strains CIAT652 and CFN42 was unique to each R. etli strain.
      These sequences were distributed throughout the chromosome as individual genes or
      chromosomal islands and in plasmids, and they encoded accessory functions, such
      as transport of sugars and amino acids, or secondary metabolism; they also
      included mobile elements and hypothetical genes. Sequences corresponding to
      symbiotic plasmids showed high levels of nucleotide identity (about 98 to 99%),
      whereas chromosomal sequences and the sequences with matches to other plasmids
      showed lower levels of identity (on average, about 90 to 95%). We concluded that
      R. etli has a pangenomic structure with a core genome composed of both
      chromosomal and plasmid sequences, including a highly conserved symbiotic
      plasmid, despite the overall genomic divergence.

PMID- 20048065
TI  - Lactobacillus reuteri 2'-deoxyribosyltransferase, a novel biocatalyst for
      tailoring of nucleosides.
AB  - A novel type II nucleoside 2'-deoxyribosyltransferase from Lactobacillus reuteri
      (LrNDT) has been cloned and overexpressed in Escherichia coli. The recombinant
      LrNDT has been structural and functionally characterized. Sedimentation
      equilibrium analysis revealed a homohexameric molecule of 114 kDa. Circular
      dichroism studies have showed a secondary structure containing 55% alpha-helix,
      10% beta-strand, 16% beta-sheet, and 19% random coil. LrNDT was thermostable with
      a melting temperature (T(m)) of 64 degrees C determined by fluorescence, circular
      dichroism, and differential scanning calorimetric studies. The enzyme showed high
      activity in a broad pH range (4.6 to 7.9) and was also very stable between pH 4
      and 7.9. The optimal temperature for activity was 40 degrees C. The recombinant
      LrNDT was able to synthesize natural and nonnatural nucleoside analogues,
      improving activities described in the literature, and remarkably, exhibited
      unexpected new arabinosyltransferase activity, which had not been described so
      far in this kind of enzyme. Furthermore, synthesis of new arabinonucleosides and
      2'-fluorodeoxyribonucleosides was carried out.

PMID- 20048064
TI  - Ecology of speciation in the genus Bacillus.
AB  - Microbial ecologists and systematists are challenged to discover the early
      ecological changes that drive the splitting of one bacterial population into two
      ecologically distinct populations. We have aimed to identify newly divergent
      lineages ("ecotypes") bearing the dynamic properties attributed to species, with
      the rationale that discovering their ecological differences would reveal the
      ecological dimensions of speciation. To this end, we have sampled bacteria from
      the Bacillus subtilis-Bacillus licheniformis clade from sites differing in solar
      exposure and soil texture within a Death Valley canyon. Within this clade, we
      hypothesized ecotype demarcations based on DNA sequence diversity, through
      analysis of the clade's evolutionary history by Ecotype Simulation (ES) and
      AdaptML. Ecotypes so demarcated were found to be significantly different in their
      associations with solar exposure and soil texture, suggesting that these and
      covarying environmental parameters are among the dimensions of ecological
      divergence for newly divergent Bacillus ecotypes. Fatty acid composition appeared
      to contribute to ecotype differences in temperature adaptation, since those
      ecotypes with more warm-adapting fatty acids were isolated more frequently from
      sites with greater solar exposure. The recognized species and subspecies of the
      B. subtilis-B. licheniformis clade were found to be nearly identical to the
      ecotypes demarcated by ES, with a few exceptions where a recognized taxon is
      split at most into three putative ecotypes. Nevertheless, the taxa recognized do
      not appear to encompass the full ecological diversity of the B. subtilis-B.
      licheniformis clade: ES and AdaptML identified several newly discovered clades as
      ecotypes that are distinct from any recognized taxon.

PMID- 20048066
TI  - Impact of temperature on ladderane lipid distribution in anammox bacteria.
AB  - Anaerobic ammonium-oxidizing (anammox) bacteria have the unique ability to
      synthesize fatty acids containing linearly concatenated cyclobutane rings, termed
      "ladderane lipids." In this study we investigated the effect of temperature on
      the ladderane lipid composition and distribution in anammox enrichment cultures,
      marine particulate organic matter, and surface sediments. Under controlled
      laboratory conditions we observed an increase in the amount of C(20) [5]
      ladderane fatty acids compared with the amount of C(18) [5]-ladderane fatty acids
      with increasing temperature and also an increase in the amount of C(18) [5]
      ladderane fatty acids compared with the amount of C(20) [5]-ladderane fatty acids
      with decreasing temperature. Combining these data with results from the natural
      environment showed a significant (R(2) = 0.85, P = <0.0001, n = 121) positive
      sigmoidal relationship between the amounts of C(18) and C(20) [5]-ladderane fatty
      acids and the in situ temperature; i.e., there is an increase in the relative
      abundance of C(18) [5]-ladderane fatty acids at lower temperatures and vice
      versa, particularly at temperatures between 12 degrees C and 20 degrees C. Novel
      shorter (C(16)) and longer (C(22) to C(24)) ladderane fatty acids were also
      identified, but their relative amounts were small and did not change with
      temperature. The adaptation of ladderane fatty acid chain length to temperature
      changes is similar to the regulation of common fatty acid composition in other
      bacteria and may be the result of maintaining constant membrane fluidity under
      different temperature regimens (homeoviscous adaptation). Our results can
      potentially be used to discriminate between the origins of ladderane lipids in
      marine sediments, i.e., to determine if ladderanes are produced in situ in
      relatively cold surface sediments or if they are fossil remnants originating from
      the warmer upper water column.

PMID- 20048067
TI  - Synergistic effects of sodium chloride, glucose, and temperature on biofilm
      formation by Listeria monocytogenes serotype 1/2a and 4b strains.
AB  - Biofilm formation by Listeria monocytogenes is generally associated with its
      persistence in the food-processing environment. Serotype 1/2a strains make up
      more than 50% of the total isolates recovered from food and the environment,
      while serotype 4b strains are most often associated with major outbreaks of human
      listeriosis. Using a microplate assay with crystal violet staining, we examined
      biofilm formation by 18 strains of each serotype in tryptic soy broth with
      varying concentrations of glucose (from 0.25% to 10.0%, wt/vol), sodium chloride
      (from 0.5% to 7.0%, wt/vol) and ethanol (from 1% to 5.0%, vol/vol), and at
      different temperatures (22.5 degrees C, 30 degrees C, and 37 degrees C). A
      synergistic effect on biofilm formation was observed for glucose, sodium
      chloride, and temperature. The serotype 1/2a strains generally formed higher
      density biofilms than the 4b strains under most conditions tested. Interestingly,
      most serotype 4b strains had a higher growth rate than the 1/2a strains,
      suggesting that the growth rate may not be directly related to the capacity for
      biofilm formation. Crystal violet was found to stain both bacterial cells and
      biofilm matrix material. The enhancement in biofilm formation by environmental
      factors was apparently due to the production of extracellular polymeric
      substances instead of the accumulation of viable biofilm cells.

PMID- 20048069
TI  - A novel mouse model for de novo Melanoma.
AB  - Nevus-associated melanomas arise from pre-existing benign lesions, but de novo
      melanomas can also develop in the absence of such lesions. Few studies have
      addressed the latter phenomenon because no animal models have been described in
      which melanomas clearly develop in a de novo manner. In this study, we have
      address this need in defining RFP-RET-transgenic mice (RET mice) as a mouse model
      for multi-step melanomagenesis that proceeds via tumor-free, benign,
      premalignant, and malignant stages. Melanomas from RET mice exhibited decreased
      expression levels of endothelin receptor B (Ednrb) compared with benign tumors.
      In RET mice that were heterozygous for Ednrb (Ednrb+/-;RET mice), >80% of the
      arising primary tumors were malignant. Life span after tumor development in the
      mice was significantly shorter than in RET mice. Lung metastasis after tumor
      development was significantly higher than in RET mice. The observed process of
      melanomagenesis in Ednrb+/-;RET mice, which proceeded without a pre-existing
      benign lesion, along with the emergent characteristics in the model after tumor
      development corresponded well with the formation of de novo melanoma in humans.
      Our findings define a novel transgenic mouse model for de novo melanoma and
      suggest that reduced expression of Ednrb might facilitate the development of de
      novo melanoma in humans.

PMID- 20048070
TI  - Matrix metalloproteinase-7 and premalignant host responses in Helicobacter pylori
      infected mice.
AB  - Helicobacter pylori-induced gastritis is the strongest singular risk factor for
      gastric adenocarcinoma. Matrix metalloproteinase-7 (MMP-7) is a proteolytic
      enzyme that can modify the intestinal microbial replicative niche as well as
      affect tumorigenesis, and H. pylori stimulates expression of MMP-7 in gastric
      epithelial cells in vitro. Utilizing a transgenic murine model of H. pylori
      mediated injury, our experiments now show that gastric inflammation is increased
      within the context of MMP-7 deficiency, which involves both Th1- and Th17
      mediated pathways. Enhanced gastritis in H. pylori-infected mmp-7-/- mice is
      strongly linked to accelerated epithelial cellular turnover. However, more severe
      inflammation and heightened proliferation and apoptosis are not dependent on MMP
      7-mediated bacterial eradication. Collectively, these studies indicate that H.
      pylori-mediated induction of MMP-7 may serve to protect the gastric mucosa from
      pathophysiologic processes that promote carcinogenesis.

PMID- 20048071
TI  - Cancer stem cell tumor model reveals invasive morphology and increased
      phenotypical heterogeneity.
AB  - The recently developed concept of cancer stem cells (CSC) sheds new light on
      various aspects of tumor growth and progression. Here, we present a mathematical
      model of malignancies to investigate how a hierarchical organized cancer cell
      population affects the fundamental properties of solid malignancies. We establish
      that tumors modeled in a CSC context more faithfully resemble human malignancies
      and show invasive behavior, whereas tumors without a CSC hierarchy do not. These
      findings are corroborated by in vitro studies. In addition, we provide evidence
      that the CSC model is accompanied by highly altered evolutionary dynamics
      compared with the ones predicted to exist in a stochastic, nonhierarchical tumor
      model. Our main findings indicate that the CSC model allows for significantly
      higher tumor heterogeneity, which may affect therapy resistance. Moreover, we
      show that therapy which fails to target the CSC population is not only
      unsuccessful in curing the patient, but also promotes malignant features in the
      recurring tumor. These include rapid expansion, increased invasion, and enhanced
      heterogeneity.

PMID- 20048072
TI  - Insulin-like growth factor-I regulates the liver microenvironment in obese mice
      and promotes liver metastasis.
AB  - Among the mechanisms implicated in the tumor-promoting effects of obesity,
      signaling by insulin-like growth factor-I (IGF-I) and insulin has received
      considerable attention. However, the emerging realization that obesity is
      associated with chronic inflammation has prompted other consideration of how the
      IGF-I axis may participate in cancer progression. In the present study, we used
      two mouse models of chronic (LID) and inducible (iLID) igf-1 gene deficiency in
      the liver to investigate the role of IGF-I in regulating the host
      microenvironment and colorectal carcinoma growth and metastasis in obese mice.
      Obese mice had a heightened inflammatory response in the liver, which was
      abolished in mice with chronic IGF-I deficiency (LID). In control animals changes
      to the hepatic microenvironment associated with obesity sustained the presence of
      tumor cells in the liver and increased the incidence of hepatic metastases after
      intrasplenic/portal inoculation of colon carcinoma cells. These changes did not
      occur in LID mice with chronic IGF-1 deficiency. In contrast, these changes
      occurred in iLID mice with acute IGF-1 deficiency, in the same manner as the
      control animals, revealing a fundamental difference in the nature of the
      requirement for IGF-1 on tumor growth and metastasis. In the setting of obesity,
      our findings imply that IGF-1 is critical to activate and sustain an inflammatory
      response in the liver that is needed for hepatic metastasis, not only through
      direct, paracrine effect on tumor cell growth, but also through indirect effects
      involving the tumor microenvironment.

PMID- 20048073
TI  - Combining human and rat sequences in her-2 DNA vaccines blunts immune tolerance
      and drives antitumor immunity.
AB  - Immune tolerance to tumor-associated self-antigens poses a major challenge in the
      ability to mount an effective cancer vaccine response. To overcome immune
      tolerance to HER-2, we formulated DNA vaccines that express both human HER-2 and
      heterologous rat Neu sequences in separate plasmids or as single hybrid
      constructs that encode HER-2/Neu fusion proteins. Candidate vaccines were tested
      in Her-2 transgenic (Tg) mice of BALB/c (BALB), BALB/cxC57BL/6 F1 (F1), or
      C57BL/6 (B6) background, which exhibit decreasing immune responsiveness to HER-2.
      Analysis of various cocktails or hybrid vaccines defined a requirement for
      particular combination of HER/2/Neu sequences to effectively prime immune
      effector cells in HER-2 Tg mice. In B6 HER-2 Tg mice, rejection of HER-2-positive
      tumors protected mice from HER-2-negative tumors, providing evidence of epitope
      spreading. Our findings show that a strategy of combining heterologous antigen
      with self-antigens could produce a potent DNA vaccine that may be applicable to
      other tumor-associated antigens.

PMID- 20048074
TI  - Nucleolar targeting of RelA(p65) is regulated by COMMD1-dependent ubiquitination.
AB  - Stimulation of the NF-kappaB pathway can have proapoptotic or antiapoptotic
      consequences, and one mechanism that determines the outcome is the nuclear
      distribution of RelA. Certain stress stimuli induce nucleolar accumulation of
      RelA thereby mediating apoptosis, whereas others induce nucleoplasmic
      accumulation and inhibition of apoptosis. Here we investigated the mechanisms
      that regulate the nuclear distribution of RelA, specifically, the role of the
      ubiquitin/proteasome system. We found that stress-induced nucleolar translocation
      of RelA is preceded by ubiquitination of the protein. We also found that chemical
      proteasome inhibitors induce the ubiquitination and nucleolar translocation of
      RelA and that this is required for the apoptotic response to these agents. We
      show that the RelA nucleolar localization signal (amino acids 27-30) is a
      critical domain for ubiquitination of the protein but that the lysine residue
      within this motif is not a direct target. We show that RelA binds COMMD1, the
      rate-limiting component of the RelA ubiquitin ligase complex, in response to
      stress. Furthermore, we show that overexpression of COMMD1 promotes stress
      mediated nucleolar targeting of RelA, whereas knockdown of COMMD1 blocks this
      effect, causing RelA to remain in the nucleoplasm. These data identify a new role
      for COMMD1 in regulating the nuclear/nucleolar distribution of RelA and suggest
      that ubiquitination acts as a signal for transport of RelA to the nucleolus.
      These findings have relevance to the design of chemopreventative/anticancer
      agents that act by targeting RelA to the nucleolar compartment.

PMID- 20048075
TI  - Recurrent focal copy-number changes and loss of heterozygosity implicate two
      noncoding RNAs and one tumor suppressor gene at chromosome 3q13.31 in
      osteosarcoma.
AB  - Osteosarcomas are copy number alteration (CNA)-rich malignant bone tumors. Using
      microarrays, fluorescence in situ hybridization, and quantitative PCR, we
      characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of
      osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma
      and contests the view that CNAs in osteosarcoma are nonrecurrent. Most (67%)
      osteo3q13.31 CNAs are deletions, with 75% of these monoallelic and frequently
      accompanied by loss of heterozygosity (LOH) in flanking DNA. Notably, these CNAs
      often involve the noncoding RNAs LOC285194 and BC040587 and, in some cases, a
      tumor suppressor gene that encodes the limbic system-associated membrane protein
      (LSAMP). Ubiquitous changes occur in these genes in osteosarcoma, usually
      involving loss of expression. Underscoring their functional significance,
      expression of these genes is correlated with the presence of osteo3q13.31 CNAs.
      Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers,
      identifying osteo3q13.31 as a generalized candidate region for tumor suppressor
      genes. Osteo3q13.31 genes may function as a unit, given significant correlation
      in their expression despite the great genetic distances between them. In support
      of this notion, depleting either LSAMP or LOC285194 promoted proliferation of
      normal osteoblasts by regulation of apoptotic and cell-cycle transcripts and also
      VEGF receptor 1. Moreover, genetic deletions of LOC285194 or BC040587 were also
      associated with poor survival of osteosarcoma patients. Our findings identify
      osteo3q13.31 as a novel region of cooperatively acting tumor suppressor genes.

PMID- 20048076
TI  - ErbB3 binding protein 1 represses metastasis-promoting gene anterior gradient
      protein 2 in prostate cancer.
AB  - Dysregulation of the developmental gene anterior gradient protein 2 (AGR2) has
      been associated with a metastatic phenotype, but its mechanism of action and
      control in prostate cancers is unknown. In this study, we show that
      overexpression of AGR2 promotes the motility and invasiveness of nonmetastatic
      LNCaP tumor cells, whereas silencing of AGR2 in the metastatic derivative C4-2B
      blocks invasive behavior. ErbB3 binding protein 1 (EBP1), a putative repressor of
      AGR2, is attenuated in prostate cancer. We show that the anti-invasive effect of
      EBP1 occurs, at least in part, through its ability to inhibit AGR2 expression.
      Mechanistic investigations indicate that EBP1 downregulates Foxa1- and Foxa2
      stimulated AGR2 transcription and decreases metastatic behavior. In contrast,
      EBP1 ablation upregulates AGR2 via Foxa1- and Foxa2-stimulated AGR2 promoter
      activity and increases metastatic behavior. In both prostate cell lines and
      primary tumors, we documented an inverse correlation between EBP1 and AGR2
      levels. Collectively, our results reveal an EBP1-Foxa-AGR2 signaling circuit with
      functional significance in metastatic prostate cancer.

PMID- 20048077
TI  - Sodium orthovanadate inhibits p53-mediated apoptosis.
AB  - Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its
      precise effects on p53 function have not been examined. Here, we show that
      vanadate exerts a potent antiapoptotic activity through both transcription
      dependent and transcription-independent mechanisms relative to other p53
      inhibitors, including pifithrin (PFT) alpha. We compared the effects of vanadate
      to PFTalpha and PFTmicro, an inhibitor of transcription-independent apoptosis by
      p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria,
      including the loss of mitochondrial membrane potential, the conformational change
      of Bax and Bak, the mitochondrial translocation of p53, and the interaction of
      p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of
      a mitochondrially targeted temperature-sensitive p53 in stable transfectants of
      SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely
      protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of
      12 Gy. Together, our findings indicated that vanadate effectively suppresses p53
      mediated apoptosis by both transcription-dependent and transcription-independent
      pathways, and suggested that both pathways must be inhibited to completely block
      p53-mediated apoptosis.

PMID- 20048078
TI  - Alpha2-macroglobulin inhibits the malignant properties of astrocytoma cells by
      impeding beta-catenin signaling.
AB  - Targets that could improve the treatment of brain tumors remain important to
      define. This study of a transformation-associated isoform of alpha2-macroglobulin
      (A2M*) and its interaction with the low-density lipoprotein receptor-related
      protein-1 (LRP1) suggests a new mechanism for abrogating the malignant potential
      of astrocytoma cells. LRP1 bound A2M* found to be associated with an inhibition
      of tumor cell proliferation, migration, invasion, spheroid formation, and
      anchorage-independent growth. Transcriptional studies implicated effects on the
      Wnt/beta-catenin signaling pathway. Notably, LRP1 antibodies could phenocopy the
      effects of A2M*. Our findings suggest a pathway of tumor suppression in
      astrocytoma that might be tractable to therapeutic exploitation.

PMID- 20048079
TI  - Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of
      breast cancer patients to neoadjuvant therapy with aromatase inhibitors.
AB  - Aromatase (CYP19) is a critical enzyme in estrogen biosynthesis and aromatase
      inhibitors (AI) are employed widely for endocrine therapy in postmenopausal women
      with breast cancer. We hypothesized that single nucleotide polymorphisms (SNPs)
      in the CYP19 gene may alter the effectiveness of AI therapy in the neoadjuvant
      setting. Genomic DNA was obtained for sequencing from 52 women pre-AI and post-AI
      treatment in this setting. Additionally, genomic DNA obtained from 82 samples of
      breast cancer and 19 samples of normal breast tissue was subjected to
      resequencing. No differences in CYP19 sequence were observed between tumor and
      germ-line DNA in the same patient. A total of 48 SNPs were identified including 4
      novel SNPs when compared with previous resequencing data. For genotype-phenotype
      association studies, we determined the levels of aromatase activity, estrone,
      estradiol, and tumor size in patients pre-AI and post-AI treatment. We defined
      two tightly linked SNPs (rs6493497 and rs7176005 in the 5'-flanking region of
      CYP19 exon 1.1) that were significantly associated with a greater change in
      aromatase activity after AI treatment. In a follow-up study of 200 women with
      early-stage breast cancer who were treated with adjuvant anastrozole, these same
      two SNPs were also associated with higher plasma estradiol levels in patients pre
      AI and post-AI treatment. Electrophoretic mobility shift and reporter gene assays
      confirmed likely functional effects of these two SNPs on transcription of CYP19.
      Our findings indicate that two common genetic polymorphisms in the aromatase gene
      CYP19 vary the response of breast cancer patients to aromatase inhibitors.

PMID- 20048080
TI  - Altered expression of neurotensin receptors is associated with the
      differentiation state of prostate cancer.
AB  - In prostate cancer, traditional treatments such as androgen response manipulation
      often provide only temporary resolution of disease, with emergence of a more
      aggressive, androgen-independent tumor following initial therapy. To treat
      recurrent disease, cell surface proteins that are specifically overexpressed on
      malignant cells may be useful for generating targeted therapeutics. Recent
      evidence suggests that neurotensin receptors (NTR) are recruited in advanced
      prostate cancer as an alternative growth pathway in the absence of androgens. In
      this study, we assessed the potential use of these receptors as targets by
      analyzing NTR expression patterns in human prostate cell lines and primary
      prostate tumor cell cultures derived from patient samples. In primary tumor cell
      cultures, NTR1 was upregulated in cells with a basal phenotype (cytokeratin
      1/5/10/14+), whereas NTR2 and NTR3 were upregulated in cells with luminal
      phenotype (cytokeratin 18+). Similar patterns of NTR expression occurred in
      benign prostate tissue sections, implicating differentiation state as a basis for
      the differences observed in tumor cell lines. Our findings support the use of
      NTRs as tools for therapeutic targeting in prostate cancers composed of both
      poorly differentiated and/or well-differentiated cells.

PMID- 20048081
TI  - Characterization of melanoma cells capable of propagating tumors from a single
      cell.
AB  - Questions persist about the nature and number of cells with tumor-propagating
      capability in different types of cancer, including melanoma. In part, this is
      because identification and characterization of purified tumorigenic subsets of
      cancer cells has not been achieved to date. Here, we report tumor formation after
      injection of single purified melanoma cells derived from three novel mouse
      models. Tumor formation occurred after every injection of individual CD34+p75-
      melanoma cells, with intermediate rates using CD34-p75- cells, and rarely with
      CD34-p75+ cells. These findings suggest that tumorigenic melanoma cells may be
      more common than previously thought and establish that multiple distinct
      populations of melanoma-propagating cells (MPC) can exist within a single tumor.
      Interestingly, individual CD34-p75- MPCs could regenerate cellular heterogeneity
      after tumor formation in mice or multiple passages in vitro, whereas CD34+p75-
      MPCs underwent self-renewal only, showing that reestablishment of tumor
      heterogeneity is not always a characteristic of individual cells capable of
      forming tumors. Functionally, single purified MPCs were more resistant to
      chemotherapy than non-MPCs. We anticipate that purification of these MPCs may
      allow a more comprehensive evaluation of the molecular features that define tumor
      forming capability and chemotherapeutic resistance in melanoma.

PMID- 20048082
TI  - Diagnostic and therapeutic potential of a human antibody cloned from a cancer
      patient that binds to a tumor-specific variant of transcription factor TAF15.
AB  - Human hybridoma technologies permit the cloning of patient antibodies that may
      have desirable qualities. In this study, we report the isolation of a natural IgG
      antibody from a stomach cancer patient that illustrates novel diagnostic and
      therapeutic uses. Human antibody PAT-BA4 recognizes a tumor-specific variant of
      the transcription factor TATA-binding protein-associated factor 15 (TAF15) that
      is expressed on the plasma membrane of stomach cancer and melanoma cells but not
      healthy tissues. TAF15 is a member of the multifunctional TET protein family
      involved in mRNA transcription, splicing, and transport that is normally
      expressed only in the cytoplasm and nucleus of fetal or adult tissue cells.
      However, in malignant cells, TET family members including TAF15 seem to be
      involved in cell adhesion and spreading. In support of this likelihood, we found
      that PAT-BA4 inhibited tumor cell motility and tumor cell adhesion. Our findings
      define a role for a tumor-specific TAF15 antigen in malignant processes.

PMID- 20048083
TI  - Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals
      with ASDs: a consensus report.
AB  - Autism spectrum disorders (ASDs) are common and clinically heterogeneous
      neurodevelopmental disorders. Gastrointestinal disorders and associated symptoms
      are commonly reported in individuals with ASDs, but key issues such as the
      prevalence and best treatment of these conditions are incompletely understood. A
      central difficulty in recognizing and characterizing gastrointestinal dysfunction
      with ASDs is the communication difficulties experienced by many affected
      individuals. A multidisciplinary panel reviewed the medical literature with the
      aim of generating evidence-based recommendations for diagnostic evaluation and
      management of gastrointestinal problems in this patient population. The panel
      concluded that evidence-based recommendations are not yet available. The
      consensus expert opinion of the panel was that individuals with ASDs deserve the
      same thoroughness and standard of care in the diagnostic workup and treatment of
      gastrointestinal concerns as should occur for patients without ASDs. Care
      providers should be aware that problem behavior in patients with ASDs may be the
      primary or sole symptom of the underlying medical condition, including some
      gastrointestinal disorders. For these patients, integration of behavioral and
      medical care may be most beneficial. Priorities for future research are
      identified to advance our understanding and management of gastrointestinal
      disorders in persons with ASDs.

PMID- 20048084
TI  - Recommendations for evaluation and treatment of common gastrointestinal problems
      in children with ASDs.
AB  - Children with autism spectrum disorders (ASDs) can benefit from adaptation of
      general pediatric guidelines for the diagnostic evaluation of abdominal pain,
      chronic constipation, and gastroesophageal reflux disease. These guidelines help
      health care providers determine when gastrointestinal symptoms are self-limited
      and when evaluation beyond a thorough medical history and physical examination
      should be considered. Children with ASDs who have gastrointestinal disorders may
      present with behavioral manifestations. Diagnostic and treatment recommendations
      for the general pediatric population are useful to consider until the development
      of evidence-based guidelines specifically for patients with ASDs.

PMID- 20048085
TI  - To treat or not to treat is the nagging question.

PMID- 20048086
TI  - Meeting the needs of adolescents: pediatric medical education and workforce
      development.

PMID- 20048087
TI  - The next generation of pediatrics.

PMID- 20048088
TI  - Policy statement--Recommended childhood and adolescent immunization schedules-
      United States, 2010.

PMID- 20048089
TI  - Should an ulnar styloid fracture be fixed following volar plate fixation of a
      distal radial fracture?
AB  - BACKGROUND: Ulnar styloid fractures often occur in association with distal radial
      fractures. The purpose of this study was to determine whether an associated ulnar
      styloid fracture following stable fixation of a distal radial fracture has any
      effect on wrist function or on the development of chronic distal radioulnar joint
      instability. METHODS: One hundred and thirty-eight consecutive patients who
      underwent surgical treatment of an unstable distal radial fracture were included
      in this study. During surgery, none of the accompanying ulnar styloid fractures
      were internally fixed. Patients were divided into nonfracture, nonbase fracture,
      and base fracture groups, on the basis of the location of the ulnar styloid
      fracture, and into nonfracture, minimally displaced (< or =2 mm), and
      considerably displaced (>2 mm) groups, according to the amount of ulnar styloid
      fracture displacement at the time of injury. Postoperative evaluation included
      measurement of grip strength and wrist range of motion; calculation of the
      modified Mayo wrist score and Disabilities of the Arm, Shoulder and Hand score;
      as well as testing for instability of the distal radioulnar joint at a mean of
      nineteen months postoperatively. RESULTS: Ulnar styloid fractures were present in
      seventy-six (55%) of the 138 patients. Forty-seven (62%) involved the nonbase
      portion of the ulnar styloid and twenty-nine (38%) involved the base of the ulnar
      styloid. Thirty-four (45%) were minimally displaced, and forty-two (55%) were
      considerably (>2 mm) displaced. We did not find a significant relationship
      between wrist functional outcomes and ulnar styloid fracture level or the amount
      of displacement. Chronic instability of the distal radioulnar joint occurred in
      two wrists (1.4%). CONCLUSIONS: An accompanying ulnar styloid fracture in
      patients with stable fixation of a distal radial fracture has no apparent adverse
      effect on wrist function or stability of the distal radioulnar joint.

PMID- 20048090
TI  - The relationship between time to surgical debridement and incidence of infection
      after open high-energy lower extremity trauma.
AB  - BACKGROUND: Urgent debridement of open fractures has been considered to be of
      paramount importance for the prevention of infection. The purpose of the present
      study was to evaluate the relationship between the timing of the initial
      treatment of open fractures and the development of subsequent infection as well
      as to assess contributing factors. METHODS: Three hundred and fifteen patients
      with severe high-energy lower extremity injuries were evaluated at eight level-I
      trauma centers. Treatment included aggressive debridement, antibiotic
      administration, fracture stabilization, and timely soft-tissue coverage. The
      times from injury to admission and operative debridement as well as a wide range
      of other patient, injury, and treatment-related characteristics that have been
      postulated to affect the risk of infection within the first three months after
      injury were studied, and differences between groups were calculated. In addition,
      multivariate logistic regression models were used to control for the effects of
      potentially confounding patient, injury, and treatment-related variables.
      RESULTS: Eighty-four patients (27%) had development of an infection within the
      first three months after the injury. No significant differences were found
      between patients who had development of an infection and those who did not when
      the groups were compared with regard to the time from the injury to the first
      debridement, the time from admission to the first debridement, or the time from
      the first debridement to soft-tissue coverage. The time between the injury and
      admission to the definitive trauma treatment center was an independent predictor
      of the likelihood of infection. CONCLUSIONS: The time from the injury to
      operative debridement is not a significant independent predictor of the risk of
      infection. Timely admission to a definitive trauma treatment center has a
      significant beneficial influence on the incidence of infection after open high
      energy lower extremity trauma.

PMID- 20048091
TI  - Outcomes of an anatomic posterolateral knee reconstruction.
AB  - BACKGROUND: Chronic posterolateral knee injuries often result in substantial
      patient morbidity and functional instability. The clinical stability and
      functional outcomes following anatomic reconstructions in patients with a chronic
      posterolateral knee injury have not been determined, to our knowledge. METHODS: A
      two-center outcomes study of sixty-four patients with grade-3 chronic
      posterolateral instability was performed. The patients were evaluated
      subjectively with the modified Cincinnati and International Knee Documentation
      Committee (IKDC) subjective scores and objectively with the IKDC objective score.
      RESULTS: Eighteen patients had an isolated posterolateral knee reconstruction,
      and forty-six patients underwent a single-stage multiple-ligament reconstruction
      that included reconstruction of one or both cruciate ligaments along with the
      posterolateral knee reconstruction. The average duration of follow-up was 4.3
      years. The fifty-four patients who were available for follow-up had an average
      total Cincinnati score of 65.7 points. A significant improvement was found
      between the preoperative and postoperative IKDC objective scores for varus
      opening at 20 degrees, external rotation at 30 degrees, reverse pivot shift, and
      single-leg hop. CONCLUSIONS: An anatomic posterolateral reconstruction resulted
      in improved clinical outcomes and objective stability for patients with a grade-3
      posterolateral knee injury.

PMID- 20048092
TI  - Prevalence of rotator cuff tear in paraplegic patients compared with controls.
AB  - BACKGROUND: Musculoskeletal injuries of the shoulder in paraplegic patients with
      long-term survival can result from overuse and/or inappropriate use of
      wheelchairs. The purpose of the present study was to evaluate the prevalence and
      risk of pathological changes in the weight-bearing shoulder girdle of paraplegic
      patients who have been wheelchair-dependent for more than thirty years in
      comparison with able-bodied volunteers. METHODS: One hundred paraplegic patients
      were matched for sex and age with a group of 100 able-bodied volunteers. Two
      hundred shoulders from each group were evaluated with use of magnetic resonance
      imaging. Collected outcome measures included a standardized clinical examination
      protocol, the Constant score, and a visual analog score for pain intensity.
      RESULTS: Shoulder function according to the Constant score was significantly
      worse in the paraplegic patients than in the able-bodied volunteers. Similarly,
      the visual analog scale pain scores were significantly worse for the paraplegic
      patients. Magnetic resonance imaging showed that the prevalence of rotator cuff
      tears in either shoulder was significantly higher in the paraplegic patients than
      in the able-bodied volunteers (63% compared with 15%), resulting in a tenfold
      higher risk of rotator cuff rupture among paraplegic patients. CONCLUSIONS: The
      present study demonstrates that the structural and functional changes of the
      shoulder joint are more severe and the risk of development of shoulder girdle
      damage is significantly higher in individuals with long-term paraplegia than in
      age-matched controls.

PMID- 20048093
TI  - Periacetabular osteotomy in patients fifty years of age or older.
AB  - BACKGROUND: Periacetabular osteotomy has been established as an effective
      treatment for early or mild osteoarthritis caused by developmental dysplasia of
      the hip. However, the optimal method of surgical reconstruction for older
      patients remains controversial. The purpose of this retrospective study was to
      evaluate the clinical and radiographic results of a curved periacetabular
      osteotomy for the treatment of developmental dysplasia of the hip in patients
      fifty years of age or older. METHODS: We evaluated forty-six consecutive hips in
      forty-two patients fifty years of age or older (the older group) who had
      developmental dysplasia of the hip and had undergone a curved periacetabular
      osteotomy between 1995 and 2006 with a minimum two-year follow-up period. The
      mean age was 54.6 years. We compared the clinical and radiographic results of
      this cohort with those of fifty hips in forty-four patients who were less than
      fifty years old (the younger group) and were managed with the same osteotomy. The
      mean age was 32.3 years. The patients were matched according to sex and Tonnis
      grade. Radiographic measurements included the center-edge angle, acetabular roof
      obliquity, acetabular head index, anterior center-edge angle, and head
      lateralization index. RESULTS: The mean Harris hip score improved from 69.6
      points preoperatively to 90.9 points postoperatively in the older group and from
      71.1 points preoperatively to 91.8 points postoperatively in the younger group.
      There were no significant differences in any of the radiographic measurements
      between the two groups preoperatively or postoperatively. The Tonnis grades
      improved in two hips and progressed in three hips in the older group and improved
      in three hips and progressed in three hips in the younger group. CONCLUSIONS:
      Satisfactory results can be obtained clinically and radiographically after curved
      periacetabular osteotomy in patients fifty years of age or older with Tonnis
      grade-1 or 2 osteoarthritis of the hip secondary to developmental dysplasia.

PMID- 20048094
TI  - Comparison of patients undergoing primary shoulder arthroplasty before and after
      the age of fifty.
AB  - BACKGROUND: The reported outcomes of shoulder arthroplasty in patients under the
      age of fifty years are worse than those in patients over fifty. While there are
      several possible explanations for this finding, we explored the possibility that
      patients who had a primary shoulder arthroplasty when they were under fifty years
      of age differed from those who had the procedure when they were over fifty with
      respect to their pre-arthroplasty self-assessed comfort and function, sex
      distribution, and specific type of arthritis. METHODS: The study group consisted
      of patients with glenohumeral arthritis who were treated with a primary shoulder
      arthroplasty by the same surgeon between 1990 and 2008. For each decade of age,
      the sex distribution, the pre-arthroplasty self-assessed shoulder comfort and
      function, and the prevalence of twelve different diagnoses were documented. We
      reviewed the series for three potential causes of worse outcomes in patients
      under fifty years of age as compared with those over fifty years of age: (1) a
      higher percentage of women, (2) a lower score for pre-arthroplasty self-assessed
      comfort and function, and (3) more complex pathological conditions. RESULTS:
      Patients under the age of fifty years were not more likely than those over fifty
      to be female or to have a lower pre-arthroplasty self-assessed comfort and
      function score, but they did have more complex pathological conditions, such as
      capsulorrhaphy arthropathy, rheumatoid arthritis, and posttraumatic arthritis.
      Only 21% of the younger patients had primary degenerative joint disease, whereas
      66% of the older patients had that diagnosis. This difference was significant (p
      < 0.000000001). CONCLUSIONS: Surgeons performing shoulder arthroplasty in
      individuals under the age of fifty should be prepared to encounter pathological
      conditions such as capsulorrhaphy arthropathy, rheumatoid arthritis, and
      posttraumatic arthritis rather than primary osteoarthritis, which is more common
      in individuals older than fifty. The pathoanatomy in these younger patients may
      complicate the surgery, the rehabilitation, and the outcome of the shoulder
      arthroplasty.

PMID- 20048095
TI  - Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with
      quantity?
AB  - BACKGROUND: As the number of studies in the literature is increasing, orthopaedic
      surgeons highly depend on meta-analyses as their primary source of scientific
      evidence. The objectives of this review were to assess the scientific quality and
      number of published meta-analyses on orthopaedics-related topics over time.
      METHODS: We conducted, in duplicate and independently, a systematic review of
      published meta-analyses in orthopaedics in the years 2005 and 2008 and compared
      them with a previous systematic review of meta-analyses from 1969 to 1999. A
      search of electronic databases (MEDLINE, EMBASE, and the Cochrane Database of
      Systematic Reviews) was performed to identify meta-analyses published in 2005 and
      2008. We searched bibliographies and contacted content experts to identify
      additional relevant studies. Two investigators independently assessed the quality
      of the studies, using the Oxman and Guyatt index, and abstracted relevant data.
      RESULTS: We included forty-five and forty-four meta-analyses from 2005 and 2008,
      respectively. While the number of meta-analyses increased fivefold from 1999 to
      2008, the mean quality score did not change significantly over time (p = 0.067).
      In the later years, a significantly lower proportion of meta-analyses had
      methodological flaws (56% in 2005 and 68% in 2008) compared with meta-analyses
      published prior to 2000 (88%) (p = 0.006). In 2005 and 2008, respectively, 18%
      and 30% of the meta-analyses had major to extensive flaws in their methodology.
      Studies from 2008 with positive conclusions used and described appropriate
      criteria for the validity assessment less often than did those with negative
      results. The use of random-effects and fixed-effects models as pooling methods
      became more popular toward 2008. CONCLUSIONS: Although the methodological quality
      of orthopaedic meta-analyses has increased in the past twenty years, a
      substantial proportion continues to show major to extensive flaws. As the number
      of published meta-analyses is increasing, a routine checklist for scientific
      quality should be used in the peer-review process to ensure methodological
      standards for publication.

PMID- 20048096
TI  - Duration of the increase in early postoperative mortality after elective hip and
      knee replacement.
AB  - BACKGROUND: There is increased early postoperative mortality after elective joint
      replacement surgery. However, the magnitude and duration of the increased
      mortality are uncertain. METHODS: Data on total knee and total hip replacement
      from the comprehensive national registries in Australia and Norway were assessed.
      Only patients between fifty and eighty years of age with osteoarthritis were
      included. Overall, the study included 81,856 patients with a total knee
      replacement and 106,254 patients with a total hip replacement. Smoothed intensity
      curves were calculated to show the change in mortality for the early
      postoperative period, whereas the effects of risk factors were studied with use
      of the nonparametric additive Aalen model. RESULTS: We found that early
      postoperative mortality was increased for the first twenty-six postoperative days
      (95% confidence interval, twenty-two to forty-one days). The excess mortality,
      compared with a baseline mortality (calculated as the average mortality from Day
      100 to Day 200), for these twenty-six days was estimated to be 0.12% (95%
      confidence interval, 0.11% to 0.14%). The most important risk factors for
      excessive early postoperative mortality were male sex and high age (more than
      seventy years of age). CONCLUSIONS: There is an increased, but low, early
      postoperative mortality following lower extremity joint replacement surgery. The
      excess mortality persists, but steadily decreases, for approximately the first
      twenty-six postoperative days.

PMID- 20048097
TI  - Risk factors for spinal cord injury during surgery for spinal deformity.
AB  - BACKGROUND: Spinal cord monitoring is now considered standard care during surgery
      for spinal deformity. Combined somatosensory and motor evoked potential
      monitoring allows the detection of early spinal cord dysfunction in most
      patients. The purpose of the current study was to identify clinical factors that
      increase the risk of intraoperative electrophysical changes and to provide
      management recommendations. METHODS: The records of 162 consecutive patients who
      underwent surgery for the treatment of spinal deformity at a tertiary referral
      center were reviewed. Electrophysical monitoring of these patients was considered
      to have been successful if reproducible signals had been obtained. Relevant
      electrophysical changes included a reduction, as compared with baseline, of >50%
      in the amplitude of the somatosensory evoked potentials; an increase, as compared
      with baseline, of >10% in the latency of the somatosensory evoked potentials; a
      loss of motor evoked potentials; and an abrupt decrease of >75% in the motor
      evoked potentials. RESULTS: One hundred and fifty-one (93%) of the 162 patients
      were monitored successfully. Four of the eleven patients with unsuccessful
      monitoring had neuromuscular scoliosis. Twelve of the 151 successfully monitored
      patients had a true electrophysical event, and two of them were found to have new
      postoperative neurologic deficits that represented a change from the findings of
      their preoperative neurologic examination. The determined causes of these
      electrophysical events included curve correction in eight patients, hypotension
      in two, direct cord trauma in one, and malposition of a pedicle screw in one. The
      patients with a true electrophysical event had a significantly higher rate of
      neurologic events than did the patients who did not have a true electrophysical
      event (p < 0.001). The rate of true electrophysical events was significantly
      higher in the patients with cardiopulmonary comorbidities than it was in the
      patients with no comorbidities (p = 0.011). CONCLUSIONS: Combined somatosensory
      and motor evoked potential monitoring effectively prevents neurologic injury in
      most children undergoing surgery for spinal deformity. Despite the potential for
      false-positive results, we recommend setting a low threshold for defining
      relevant electrophysical changes. Rapid intervention can reverse these changes
      and avoid potentially serious neurologic complications. Patients with
      cardiopulmonary comorbidities may be at a higher risk for having relevant
      electrophysical events.

PMID- 20048098
TI  - The effect of short tandem repeat loci and low selenium levels on endemic
      osteoarthritis in China.
AB  - BACKGROUND: The etiology of Kashin-Beck disease, an endemic osteochondropathy, is
      unknown. Environmental factors, including selenium deficiency, have been proposed
      as potential risk factors, but the onset and frequency of this disease vary among
      groups with similar environmental exposures. Some cases of osteoarthritis that
      share similar pathological features with Kashin-Beck disease have been associated
      with specific chromosomal short tandem repeats. In order to better understand the
      pathogenesis of Kashin-Beck disease, we examined fifteen short tandem-repeat loci
      on chromosomes 2 and 11 in patients and control subjects, and assessed the
      interaction between genetic variants and selenium deficiency. METHODS: DNA
      samples from 129 patients with Kashin-Beck disease (the Kashin-Beck disease
      group), seventy-two healthy control subjects from areas where Kashin-Beck disease
      was endemic (control group 1), and forty-eight healthy control subjects from
      areas where Kashin-Beck disease was not endemic (control group 2) were collected,
      and fifteen short tandem repeats were genotyped. The allele frequencies of these
      short tandem-repeat loci were compared among the three groups. Differences in
      selenium concentrations among patients and controls were also examined, and the
      interaction between low selenium levels and the susceptibility loci was
      calculated. RESULTS: The percentages of subjects with short tandem-repeat alleles
      D2S338 (290 bp) and D11S4094 (194 bp) in the Kashin-Beck disease group were
      significantly lower than those in the two control groups, while percentages of
      D2S305 (320 bp) and D11S4149 (221 bp) were higher than those in the control
      groups. The percentage of subjects with D11S4149 (217 bp) in the Kashin-Beck
      disease group was only significantly lower than that in control group 1. The
      percentages of subjects with D11S912 (106 bp) in both the Kashin-Beck disease
      group and control group 1 were significantly lower than those in control group 2.
      Selenium concentrations in serum from subjects in the Kashin-Beck disease group
      and control group 1 were similar, but both were lower than that of control group
      2. The odds ratios of low selenium in serum were between 1.2 and 1.6 (p > 0.05),
      and the odds ratios of interactions between low selenium and the susceptibility
      loci ranged between 0.8 and 1.4 (p > 0.05). CONCLUSIONS: Our results suggest that
      variants of the chromosomal short tandem repeats D11S4094, D11S4149, D2S338, and
      D2S305 are associated with Kashin-Beck disease, and that the frequency of D11S912
      polymorphisms varies in geographic areas with high and low prevalences of Kashin
      Beck disease. Our data did not show a significant interaction between low
      selenium and the susceptibility loci in the occurrence of Kashin-Beck disease.
      The interaction between genetic variabilities and environmental factors can be
      complex, but our results suggest that genetic factors may be more important than
      selenium deficiency in the pathogenesis of Kashin-Beck disease.

PMID- 20048099
TI  - Plantar pressures in patients with and without lateral foot pain after lateral
      column lengthening.
AB  - BACKGROUND: Lateral column lengthening, a commonly used adjuvant for the
      reconstruction of adult flatfoot deformity, can lead to postoperative complaints
      of lateral plantar pain or discomfort. We hypothesized that patients with such
      symptoms would have increased lateral plantar pressures when compared with
      matched controls without these symptoms. METHODS: Ten subjects who had undergone
      lateral column lengthening and were experiencing pain or discomfort in the
      plantar-lateral aspect of the foot were selected. Controls who had undergone
      lateral column lengthening but who were not experiencing such symptoms were
      matched for age, sex, accessory reconstructive procedures, and time from surgery.
      At the time of the present study, the patients had been followed for at least two
      years after the reconstruction and had had removal of hardware. Radiographs of
      each foot were assessed before and after surgery. The patients completed the
      Short Form-36 (SF-36) and Foot and Ankle Outcome Score surveys, and standing
      plantar pressure measurements were obtained. Average mean pressure, peak
      pressure, and maximum force were assessed at twelve anatomic regions and the two
      groups were compared. RESULTS: There were no significant preoperative differences
      between the two groups in terms of radiographic parameters. Patients with pain
      had significantly lower SF-36 Physical Health Summary scores (p < 0.05), SF-36
      Physical Function Subscale scores (p < 0.05), and average Foot and Ankle Outcome
      Scores (p < 0.05). Patients with pain had significantly higher lateral midfoot
      average mean pressure (p < 0.05), peak pressure (p < 0.05), and maximum force (p
      < 0.05). No differences were found in the hindfoot or forefoot regions.
      CONCLUSIONS: Patients who have undergone lateral column lengthening and who
      experience lateral plantar pain have increased plantar pressure values in the
      lateral aspect of the midfoot. The increased pressures in this area cannot be
      accounted for solely by radiographic or demographic factors.

PMID- 20048101
TI  - Assessment of the radii of the medial and lateral femoral condyles in varus and
      valgus knees with osteoarthritis.
AB  - BACKGROUND: Understanding the relationship between the radii of the medial and
      lateral femoral condyles in varus and valgus knees is important for aligning the
      femoral component and for restoring kinematics in total knee arthroplasty. The
      purpose of this study was to test the hypothesis that the asymmetry between the
      radii of the medial and lateral femoral condyles in varus and valgus knees with
      osteoarthritis is small enough to be clinically unimportant. METHODS: A magnetic
      resonance imaging scan was obtained with use of a biplanar, rotational alignment
      protocol in a consecutive series of subjects with end-stage osteoarthritis prior
      to total knee arthroplasty. The alignment protocol oriented the scanning plane so
      that both condyles were imaged in a plane perpendicular to the primary femoral
      axis of the knee about which the tibia flexes and extends. The study included 155
      varus knees and forty-four valgus knees. Radii were calculated from the area of
      the best-fit circle overlaid from 10 degrees to 160 degrees on the subchondral
      corticocancellous bone interface of the medial and lateral femoral condyles. The
      radius of a condyle was the average of the radii on four adjacent images that
      showed the femoral condyle with the largest curvature. RESULTS: In the 155 varus
      knees, the radius of the lateral condyle was an average of 0.1 mm larger than
      that of the medial condyle (p = 0.003). In the forty-four valgus knees, the
      radius of the lateral condyle was an average of 0.2 mm larger than that of the
      medial condyle (p < 0.006). There was a strong association between the radii of
      the medial and lateral femoral condyles in both the varus (r(2) = 0.9210) and the
      valgus (r(2) = 0.9129) knees. CONCLUSIONS: As determined by imaging of the
      femoral condyles perpendicular to the primary femoral axis of the knee, the
      asymmetry between the radii of the medial and lateral femoral condyles in varus
      and valgus knees with end-stage osteoarthritis was < or =0.2 mm, which is small
      enough to be considered clinically unimportant when aligning a total knee
      prosthesis.

PMID- 20048100
TI  - Cognition following computer-assisted total knee arthroplasty: a prospective
      cohort study.
AB  - BACKGROUND: A substantial number of patients experience postoperative cognitive
      changes following total joint arthroplasty. The change in mental status may be
      the result of fat and bone-marrow-debris embolization. We hypothesized that the
      use of computer-assisted total knee arthroplasty, which does not involve the use
      of intramedullary alignment rods, would produce less fat and bone-marrow-debris
      embolization and, hence, fewer changes in mental status. METHODS: Forty-seven
      patients who underwent total knee arthroplasty with use of a computer-assisted
      navigation system and forty-eight patients who underwent conventional total knee
      arthroplasty without the assistance of computer navigation were followed
      prospectively. The validated Folstein Mini-Mental State Examination (MMSE) was
      used to assess the mental status of the patients. The test was administered
      preoperatively, serially postoperatively while the patient was in the hospital,
      and at six months. Medication and oxygen requirements were recorded. RESULTS: On
      the basis of the numbers studied, no significant differences in postoperative
      pain-medication or oxygen requirements were found between the group treated with
      computer-assisted navigation (the navigation group) and the group treated with
      conventional total knee arthroplasty (the control group). The mean postoperative
      MMSE score was 88.9 points in the navigation group and 89.3 points in the control
      group (p = 0.844). Twenty-five patients in the navigation group and thirty-six
      patients in the control group completed the test at six months. The mean score at
      that time was 95.3 points in the navigation group and 96.3 points in the control
      group (p = 0.514). CONCLUSIONS: Further research is needed to determine if fat
      and bone-marrow-debris embolization is truly decreased by the use of computer
      assisted total knee arthroplasty and if such a reduction has any clinical
      relevance.

PMID- 20048102
TI  - The influence of head size and sex on the outcome of Birmingham hip resurfacing.
AB  - BACKGROUND: Hip resurfacing has gained popularity for the treatment of young and
      active patients who have arthritis. Recent literature has demonstrated an
      increased rate of revision among female patients as compared with male patients
      who have undergone hip resurfacing. The aim of the present study was to identify
      any differences in survival or functional outcome between male and female
      patients with osteoarthritis who were managed with metal-on-metal hip
      resurfacing. METHODS: A prospective collection of data on all patients undergoing
      Birmingham Hip Resurfacing at a single institution was commenced in July 1997. On
      the basis of the inclusion and exclusion criteria, 1826 patients (2123 hips,
      including 799 hips in female patients and 1324 hips in male patients) with a
      diagnosis of osteoarthritis who had undergone the procedure between July 1997 and
      December 2008 were identified. The variables of age, sex, preoperative Oxford Hip
      Score, component size used, surgical approach, lead surgeon, and surgeon
      experience were analyzed. A multivariate Cox proportional hazard survival model
      was used to identify which variables were most influential for determining
      revision. RESULTS: The mean duration of follow-up was 3.46 years (range, 0.03 to
      10.9 years). The five-year cumulative survival rate for the 655 hips that were
      followed for a minimum of five years was 97.5% (95% confidence interval, 96.3% to
      98.3%). There were forty-eight revisions. Revision was significantly associated
      with female sex (hazard rate, 2.03 [95% confidence interval, 1.15 to 3.58]; p =
      0.014) and decreasing femoral component size (hazard rate per 4-mm decrease in
      size, 4.68 [95% confidence interval, 4.36 to 5.05]; p < 0.001). Revision was not
      associated with age (p = 0.88), surgeon (p = 0.41), surgeon experience (p =
      0.30), or surgical approach (p = 0.21). A multivariate analysis including the
      covariates of sex, age, surgeon, surgeon experience, surgical approach, and
      femoral component size demonstrated that sex was no longer significantly
      associated with revision when femoral component size was included in the model (p
      = 0.37). Femoral component size alone was the best predictor of revision when all
      covariates were analyzed (hazard rate per 4-mm decrease in size, 4.87 [95%
      confidence interval, 4.37 to 5.42]; p < 0.001). CONCLUSIONS: The present study
      demonstrates that although female patients initially may appear to have a greater
      risk of revision, this increased risk is related to differences in the femoral
      component size and thus is only indirectly related to sex. Patient selection for
      hip resurfacing is best made on the basis of femoral head size rather than sex.

PMID- 20048103
TI  - Ultrasonographic findings in hips with a positive Ortolani sign and their
      relationship to Pavlik harness failure.
AB  - BACKGROUND: In developmental dysplasia, Pavlik harness treatment of hips with a
      positive Ortolani sign fails in up to 40% of such patients; however, no study has
      described factors for failure associated with ultrasonographic parameters. The
      goal of this study was to describe unique ultrasonographic markers in hips with a
      positive Ortolani sign that are associated with Pavlik harness failure. METHODS:
      A retrospective review was performed of all patients less than six months old who
      were treated for developmental dysplasia of the hip with a Pavlik harness from
      1991 to 2005 at a single institution. Inclusion criteria for this study were
      patients with a hip that was dislocated but reducible (a positive Ortolani sign),
      treatment with a Pavlik harness, and an ultrasound examination performed within
      four weeks after the initiation of treatment. The initial coronal ultrasound
      studies were graded with use of the Graf classification, the percentage of
      femoral head coverage, labral morphology, and two new measurements: superior
      femoral head displacement relative to the labrum and total femoral head
      displacement. RESULTS: Eighty-five patients with 115 hips fitting the inclusion
      criteria were identified. Pavlik harness treatment was successful in seventy-two
      hips (63%) and failed in forty-three hips (37%). Increased beta angle, decreased
      femoral head coverage, an inverted labrum, decreased superior femoral head
      displacement relative to the labrum, and decreased total femoral head
      displacement were significantly correlated with Pavlik harness failure (p < 0.001
      for all). A finding of 0 degrees of superior femoral head displacement relative
      to the labrum was seen in 98% of the hips with successful Pavlik harness
      treatment. Total femoral head displacement of less than -30 degrees was found in
      89% of the hips with a failure of Pavlik harness treatment. CONCLUSIONS: We
      identified two new objective measurements on static ultrasound examinations of
      the hip that are associated with the outcome of Pavlik harness treatment in
      patients with developmental dysplasia and a positive Ortolani sign. A femoral
      head positioned below the labrum is strongly associated with success of the
      Pavlik harness treatment, whereas a hip with a femoral head that is located
      substantially superior and lateral to the labrum is associated with Pavlik
      harness treatment failure. The presence of a deficient cartilaginous anlage and
      an inverted labrum may provide a pathoanatomical explanation for Pavlik harness
      treatment failure.

PMID- 20048104
TI  - Coagulation abnormalities in Legg-Calve-Perthes disease.
AB  - BACKGROUND: Legg-Calve-Perthes disease is a pediatric disorder characterized by
      osteonecrosis of the proximal femoral epiphysis. The etiology probably involves
      successive vascular occlusions, in which hypercoagulable disorders may play a
      role. We evaluated the etiologic role of thrombophilia in Legg-Calve-Perthes
      disease in a pediatric population. METHODS: One hundred and sixty-nine
      consecutive patients who had been diagnosed with Legg-Calve-Perthes disease at
      two centers in Rotterdam, the Netherlands, when they were between 1.5 and 13.5
      years of age were identified between 2000 and 2003. The study also included two
      control groups: 474 subjects (16.3 to 73.1 years of age) from a population-based
      case-control study on the etiology of venous thrombosis as well as thirty-eight
      children (1.8 to 18.8 years of age) who were treated for asthma at one of the
      centers. We determined levels of protein C, protein S, factor VIII, and
      fibrinogen and tested for the factor V Leiden and prothrombin G20210A mutations.
      We calculated age and sex-adjusted odds ratios as measures of the relative risk
      of the development of Legg-Calve-Perthes disease. RESULTS: The incidence of Legg
      Calve-Perthes disease was increased in the presence of the factor V Leiden
      mutation (odds ratio, 3.3; 95% confidence interval, 1.6 to 6.7), in the presence
      of the prothrombin G20210A mutation (odds ratio, 2.6; 95% confidence interval,
      1.0 to 6.3), in association with elevated levels of factor VIII (>150 IU/dL)
      (odds ratio, 7.5; 95% confidence interval, 2.2 to 25.2), and in association with
      protein S deficiency (<67 U/dL) (odds ratio, 2.8; 95% confidence interval, 0.7 to
      10.8). Neither high levels of fibrinogen (>4.0 g/L) nor protein C deficiency (<
      or =55 U/dL) had an apparent effect on the risk of Legg-Calve-Perthes disease.
      (Odds ratios were adjusted for age and sex.) Overall, males had a 2.4 times
      higher risk of Legg-Calve-Perthes disease developing than did females. The effect
      of the factor V Leiden mutation, high levels of fibrinogen, and increasing levels
      of factor VIII was stronger in males than in females. The risk of Legg-Calve
      Perthes disease increased with an increasing number of coagulation abnormalities
      in males but not in females. CONCLUSIONS: There appears to be a thrombotic
      component in the etiology of Legg-Calve-Perthes disease.

PMID- 20048105
TI  - In vitro cytotoxic effects of benzalkonium chloride in corticosteroid injection
      suspension.
AB  - BACKGROUND: Some deleterious effects on cartilage and even severe arthropathy
      have been reported after intra-articular corticosteroid injections. The objective
      of the present in vitro study was to determine if an injectable corticosteroid
      suspension is toxic to articular chondrocytes and synovial cells. METHODS: Human
      and bovine articular chondrocytes, bovine synovial cells, mouse C3H10T1/2 cells,
      and human osteosarcoma MG-63 cells were treated for thirty minutes in monolayer
      or suspension culture with an injectable corticosteroid suspension or its
      chemical components, including betamethasone sodium phosphate, betamethasone
      acetate, and benzalkonium chloride (as preservative). Cell viability was
      determined by means of microscopy or flow cytometry analysis. RESULTS: In
      monolayer culture, the betamethasone corticosteroids per se did not cause cell
      death, whereas benzalkonium chloride caused death of articular chondrocytes. In
      suspension culture, betamethasone sodium phosphate at dosages of as high as 6
      mg/mL did not cause significant death of human or bovine articular chondrocytes
      (p > 0.05). In contrast, benzalkonium chloride caused a death rate of 10.6% in
      human articular chondrocytes at a dosage of 10 microg/mL (p < 0.01), 21.0% at a
      dosage of 13.3 microg/mL (p < 0.01), and 99.3% and 99.4% at dosages of 20 and 200
      microg/mL, respectively (p < 0.001 for both). Similarly, benzalkonium chloride
      caused death of bovine articular chondrocytes, bovine synovial cells, C3H10T1/2
      cells, and MG-63 cells in a dose-dependent manner. When treated with a
      combination of betamethasone sodium phosphate and 200 microg/mL benzalkonium
      chloride, >99% of human or bovine articular chondrocytes were dead (p < 0.001).
      CONCLUSIONS: The injectable corticosteroid suspension caused death in in vitro
      culture of human and bovine articular chondrocytes as well as bovine synovial
      cells because of its preservative benzalkonium chloride. The betamethasone
      corticosteroids per se did not cause significant chondrocyte death under the
      conditions tested.

PMID- 20048106
TI  - The value of serum procalcitonin level for differentiation of infectious from
      noninfectious causes of fever after orthopaedic surgery.
AB  - BACKGROUND: Early diagnosis of postoperative orthopaedic infections is important
      in order to rapidly initiate adequate antimicrobial therapy. There are currently
      no reliable diagnostic markers to differentiate infectious from noninfectious
      causes of postoperative fever. We investigated the value of the serum
      procalcitonin level in febrile patients after orthopaedic surgery. METHODS: We
      prospectively evaluated 103 consecutive patients with new onset of fever within
      ten days after orthopaedic surgery. Fever episodes were classified by two
      independent investigators who were blinded to procalcitonin results as infectious
      or noninfectious origin. White blood-cell count, C-reactive protein level, and
      procalcitonin level were assessed on days 0, 1, and 3 of the postoperative fever.
      RESULTS: Infection was diagnosed in forty-five (44%) of 103 patients and involved
      the respiratory tract (eighteen patients), urinary tract (eighteen), joints
      (four), surgical site (two), bloodstream (two), and soft tissues (one). Unlike C
      reactive protein levels and white blood-cell counts, procalcitonin values were
      significantly higher in patients with infection compared with patients without
      infection on the day of fever onset (p = 0.04), day 1 (p = 0.07), and day 3 (p =
      0.003). Receiver-operating characteristics demonstrated that procalcitonin had
      the highest diagnostic accuracy, with a value of 0.62, 0.62, and 0.71 on days 0,
      1, and 3, respectively. In a multivariate logistic regression analysis,
      procalcitonin was a significant predictor for postoperative infection on days 0,
      1, and 3 of fever with an odds ratio of 2.3 (95% confidence interval, 1.1 to
      4.4), 2.3 (95% confidence interval, 1.1 to 5.2), and 3.3 (95% confidence
      interval, 1.2 to 9.0), respectively. CONCLUSIONS: Serum procalcitonin is a
      helpful diagnostic marker supporting clinical and microbiological findings for
      more reliable differentiation of infectious from noninfectious causes of fever
      after orthopaedic surgery.

PMID- 20048107
TI  - Amplified inflammatory response to sequential hemorrhage, resuscitation, and
      pulmonary fat embolism: an animal study.
AB  - BACKGROUND: The objective of this study was to assess the role of pulmonary fat
      embolism caused by intramedullary pressurization of the femoral canal in the
      development of acute lung injury in the setting of acute hemorrhagic shock and
      resuscitation. METHODS: Thirty New Zealand White rabbits were randomly assigned
      to one of four groups: (1) nine animals in which hemorrhagic shock was induced by
      carotid bleeding, resuscitation was performed, and the femoral canal was reamed
      and pressurized with bone cement to induce fat embolism (hemorrhagic shock and
      resuscitation/fat embolism [HR/FE] group); (2) six animals in which shock was
      induced by carotid bleeding, resuscitation was performed, and a sham knee
      incision was made and closed without drilling, reaming, or pressurization
      (hemorrhagic shock and resuscitation [HR] group); (3) eight animals in which no
      hemorrhage or shock was induced but the femoral canal was reamed and pressurized
      with bone cement to induce fat embolism (fat embolism [FE] group); and (4) seven
      animals that had a three-hour ventilation period followed by a sham knee incision
      (control group). The animals were ventilated for four hours following closure.
      Flow cytometry with use of antibodies against CD45 and CD11b was performed to
      test neutrophil activation in whole blood. Histological examination of lung
      specimens was also performed. Plasma and bronchoalveolar lavage fluid were
      analyzed for monocyte chemotactic peptide-1 and interleukin-8 levels with use of
      the ELISA (enzyme-linked immunosorbent assay) method. RESULTS: Three animals in
      the HR/FE group died immediately after canal pressurization and were excluded.
      CD11b mean channel fluorescence was significantly elevated, as compared with
      baseline, only in the HR/FE group at two hours (p = 0.025) and four hours (p =
      0.024) after knee closure. Histological analysis showed that only the HR/FE (p <
      0.001) and HR (p = 0.010) groups had significantly greater infiltration of
      alveoli by polymorphonuclear leukocytes as compared with that in the controls. No
      significant differences in plasma cytokine levels were found between the groups.
      Only the HR/FE group had significantly higher interleukin-8 (p = 0.020) and
      monocyte chemotactic peptide-1 (p = 0.004) levels in the bronchoalveolar lavage
      fluid as compared with those in the controls. CONCLUSIONS: Fat embolism from
      canal pressurization alone did not activate a pulmonary inflammatory response.
      The combination of hemorrhagic shock, resuscitation, and fat embolism elicited
      neutrophil activation, infiltration of alveoli by polymorphonuclear leukocytes,
      and inflammatory cytokine expression in bronchoalveolar lavage fluid.

PMID- 20048108
TI  - Cytotoxic effect of zoledronic acid-loaded bone cement on giant cell tumor,
      multiple myeloma, and renal cell carcinoma cell lines.
AB  - BACKGROUND: Local recurrence with subsequent osteolysis is a problem after
      intralesional curettage of giant cell tumor of bone, myeloma, and metastatic
      carcinoma. The bisphosphonate zoledronic acid (zoledronate) has been shown to
      reduce osteoclast activity, and its local administration is a potentially
      attractive therapy, especially for the osteoclast-rich giant cell tumor. The aim
      of this study was to analyze the elution dynamics of zoledronic acid release from
      acrylic bone cement and its in vitro antitumor efficacy. METHODS: Various
      concentrations of zoledronic acid were mixed with bone cement and placed in
      distilled water. The concentration in the water was measured daily for fourteen
      days. The cytotoxic effects of the dissolved zoledronic acid on cultures of
      multiple myeloma, giant cell tumor, and renal cell carcinoma cells were tested
      with use of the MTT assay (tetrazolium [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] dye) and analyzed according to the zoledronic acid
      concentration and the elapsed time. RESULTS: The release of zoledronic acid was
      greatest during the first twenty-four hours for all concentrations and decreased
      rapidly during the next forty-eight hours to reach a plateau after four days. The
      proliferation assay (MTT) showed zoledronic acid to have significant cytotoxicity
      in cultures of stromal giant cell tumor, multiple myeloma, and renal cell
      carcinoma cells. In addition, zoledronic acid decreased the number of viable
      tumor cells in a dose-dependent manner. Renal cell carcinoma from bone (RBM1-IT4)
      and stromal giant cell tumor of bone were more susceptible to zoledronic acid
      than was multiple myeloma. CONCLUSIONS: The method presented in our study is a
      reproducible technique for evaluating zoledronic acid elution from bone cement
      and determining its impact on tumor growth. Zoledronic acid is released from bone
      cement, remains biologically active despite the polymerization of cement, and
      inhibits the in vitro growth of cell lines from giant cell tumor of bone,
      myeloma, and renal cell carcinoma.

PMID- 20048109
TI  - Predictability of the fulcrum bending radiograph in scoliosis correction with
      alternate-level pedicle screw fixation.
AB  - BACKGROUND: The fulcrum bending radiograph accurately predicts scoliosis curve
      correction in patients with thoracic adolescent idiopathic scoliosis who are
      managed with hooks. We assessed the predictive value of the fulcrum bending
      radiograph in the context of alternate-level pedicle screw fixation of the
      scoliotic spine. METHODS: A prospective radiographic analysis of patients with
      thoracic adolescent idiopathic scoliosis who were managed operatively with
      alternate-level pedicle screw fixation at a single institution was performed. The
      Cobb angle was measured on posteroanterior standing coronal radiographs that were
      made preoperatively and one week postoperatively. The fulcrum flexibility
      percentage and the fulcrum bending correction index percentage were calculated.
      RESULTS: Forty-two patients were assessed. The mean age at the time of surgery
      was 14.6 years, and the mean number of fused levels was 9.4. On the preoperative
      radiographs, the mean values for the standing Cobb angle, the fulcrum bending
      radiograph Cobb angle, and fulcrum flexibility were 57.9 degrees, 21.8 degrees,
      and 62.7%, respectively. On the one-week postoperative radiographs, the mean Cobb
      angle was 15.4 degrees, the mean curve correction was 73.4%, and the mean fulcrum
      bending correction index was 122.1%. A significant, positive correlation was
      noted between the fulcrum bending radiograph angle and the fulcrum bending
      correction index, indicating that the fulcrum bending radiograph could predict
      the correction of flexible curves; however, for stiff curves, pedicle screws
      could provide more correction than the fulcrum bending radiograph predicted.
      CONCLUSIONS: To our knowledge, this is the first study to demonstrate the
      predictive value of the fulcrum bending radiograph in the context of alternate
      level pedicle screw fixation in patients with adolescent idiopathic scoliosis.
      Curve flexibility may dictate the degree of the fulcrum bending correction index,
      whereby a curve that is less flexible may achieve a greater fulcrum bending
      correction index. The fulcrum bending radiograph has potential predictive
      utility. In addition, pedicle screw constructs appear to have a better ability to
      correct scoliosis in comparison with hooks and hybrid constructs.

PMID- 20048110
TI  - The use of rhBMP-2 for the treatment of congenital pseudarthrosis of the tibia: a
      case series.

PMID- 20048111
TI  - Rapid chondrolysis of the knee after anterior cruciate ligament reconstruction: a
      case report.

PMID- 20048112
TI  - Tetrafocal bone transport of the tibia with circular external fixation: a case
      report.

PMID- 20048113
TI  - Induced membranes--a staged technique of bone-grafting for segmental bone loss: a
      report of two cases and a literature review.

PMID- 20048114
TI  - Growth modulation by means of anterior tethering resulting in progressive
      correction of juvenile idiopathic scoliosis: a case report.

PMID- 20048115
TI  - Arteriovenous malformation infiltrating the extensor hallucis longus tendon: a
      case report.

PMID- 20048116
TI  - American Academy of Orthopaedic Surgeons clinical practice guideline on the
      treatment of carpal tunnel syndrome.

PMID- 20048117
TI  - Assessment of hip and knee muscle function in orthopaedic practice and research.
AB  - Isometric evaluation of hip and knee muscle strength can be a useful objective
      assessment tool in the clinic and may be preferred over other forms of dynamic
      muscle testing, such as isokinetic assessment or variable-resistance weight
      lifting. Assessment of isometric strength with use of a handheld dynamometer
      requires little skill and is easily administered, relatively inexpensive, valid,
      reliable, and functional; thus, it could be easily integrated into routine
      clinical examinations. Surface electrical stimulation, electromyography, and
      ultrasonography can be used in conjunction with isometric muscle testing for the
      identification of neuromuscular factors influencing muscle force generation.
      Further research is warranted to investigate the neural and/or muscular
      impairments associated with hip and knee muscle weakness in orthopaedic
      populations, with the ultimate goal of improving rehabilitation strategies.

PMID- 20048118
TI  - Perioperative strategies for decreasing infection: a comprehensive evidence-based
      approach.

PMID- 20048119
TI  - Prevalence of cancer in female orthopaedic surgeons in the United States.

PMID- 20048120
TI  - Proposals for change in orthopaedic education: recommendations from an
      orthopaedic residency directors' peer forum.

PMID- 20048121
TI  - What's new in sports medicine.

PMID- 20048122
TI  - Lack of independent relationship between age-related kidney function decline and
      carotid intima-media thickness in a healthy Chinese population.
AB  - BACKGROUND: Ageing-related decline in kidney function is an independent predictor
      for cardiovascular events and death. However, the underlying mechanism is not
      clear. The purpose of this study was to identify the associations between ageing
      related decline in kidney function and carotid intima-media thickness (IMT) in a
      healthy Chinese population with normal kidney function and with no cardiovascular
      disease. Methods. In cross-sectional study, we examined 852 participants (aged 30
      98 years, 392 men) free from cardiovascular disease and with an estimated
      glomerular filtration rate (eGFR) >60 ml/min/1.73 m(2). Kidney function was
      estimated by using two markers: eGFR, which was evaluated by the creatinine-based
      Modification of Diet in Renal Disease (MDRD) Study equation, and cystatin C
      (CYSC) level. Participants were categorized into quartiles (I-IV) of eGFR and
      CYSC with quartile I representing the best kidney function (the highest eGFR
      quartiles and lowest CYSC). Carotid IMT was analysed using M-mode
      ultrasonography, and elevated carotid IMT was defined as measures above the 75th
      percentile of the sample distribution (0.9 mm). RESULTS: CYSC was significantly
      correlated with age in both males (r = 0.441, P < 0.001) and females (r = 0.634,
      P < 0.001). However, eGFR was only significantly related with age in females (r =
      -0.173, P < 0.001). CYSC was significantly associated with elevated carotid IMT
      in an unadjusted model in quartiles III and IV; the odds ratios (95% CI) were
      3.64 (2.116-6.261) and 6.407 (3.786-10.84), respectively. However, this
      association was significantly attenuated by age adjustment and was lost after
      full adjustment of age and all other confounding variables including sex, body
      mass index, systolic blood pressure, diastolic blood pressure, triglyceride,
      total cholesterol, high-density lipoprotein, low-density lipoprotein, albumin,
      fasting blood glucose, log C-reactive protein, log interleukin-6 and fibrinogen.
      No significant association was found between quartiles of eGFR and higher IMT.
      CONCLUSIONS: Ageing is a major factor contributing to decline in kidney function
      in a healthy population. There is no independent relationship between ageing
      related decline in kidney function and atherosclerosis in a population with
      normal kidney function.

PMID- 20048123
TI  - CD155 is involved in negative selection and is required to retain terminally
      maturing CD8 T cells in thymus.
AB  - During their final maturation in the medulla, semimature single-positive (SP)
      thymocytes downregulate activation markers and subsequently exit into the
      periphery. Although semimature CD4(+) SP cells are sensitive to negative
      selection, the timing of when negative selection occurs in the CD8 lineage
      remains elusive. We show that the abundance of terminally matured CD8(+) SP cells
      in adult thymus is modulated by the genetic background. Moreover, in BALB/c mice,
      the frequency of terminally matured CD8(+) SP cells, but not that of CD4(+) SP
      cells present in thymus, varies depending on age. In mice lacking expression of
      the adhesion receptor CD155, a selective deficiency of mature CD8(+) SP
      thymocytes was observed, emerging first in adolescent animals at the age when
      these cells start to accumulate in wild-type thymus. Evidence is provided that
      the mature cells emigrate prematurely when CD155 is absent, cutting short their
      retention time in the medulla. Moreover, in nonmanipulated wild-type mice,
      semimature CD8(+) SP thymocytes are subjected to negative selection, as reflected
      by the diverging TCR repertoires present on semimature and mature CD8(+) T cells.
      In CD155-deficient animals, a shift was found in the TCR repertoire displayed by
      the pool of CD8(+) SP cells, demonstrating that CD155 is involved in negative
      selection.

PMID- 20048125
TI  - Birch pollen immunotherapy leads to differential induction of regulatory T cells
      and delayed helper T cell immune deviation.
AB  - Correction of an imbalance between allergen-specific T cell subsets is considered
      a critical event in establishing allergen tolerance by specific immunotherapy
      (SIT). In a comprehensive, longitudinal study, distinct T cell populations and Ig
      subtypes were analyzed in subjects allergic to birch pollen during decisive time
      points of SIT (i.e., induction and maintenance phase), as well as in and out of
      birch pollen season. An increase in Bet v 1-specific, IL-10-secreting T cells,
      fulfilling the criteria of inducible type 1 regulatory T (Tr1) cells, was
      observed by the end of the induction phase; this resulted in a decreased ratio of
      allergen-specific IL-5(+) Th2/Tr1 cells. In contrast, CD4(+)CD25(+)CD127(low)
      regulatory T cell numbers did not change. Furthermore, enhanced concentrations of
      allergen-specific IgG Abs were observed, whereas allergen-specific IgE and IgA
      levels remained unchanged. After 1 y of SIT, a reduced ratio of allergen-specific
      Th2/IFN-gamma(+) Th1 cells was apparent. Although untreated and SIT-treated
      allergic subjects developed enhanced Th2 cell responses during birch pollen
      season, only SIT-treated patients experienced elevated numbers of allergen
      specific Tr1 cells, which were associated with reduced skin prick test reactivity
      and diminished clinical symptoms. In coculture assays, allergen-specific Tr1
      cells showed an IL-10- and dose-dependent inhibition of CD4(+)CD25(-) T effector
      cells. Thus, SIT has differential effects on regulatory T cell subsets, resulting
      in an early induction of allergen-specific Tr1 cells associated with an increase
      in allergen-specific IgG, and it leads to a delayed shift from an allergen
      specific Th2- to a Th1-dominated immune response.

PMID- 20048124
TI  - Commensal microbiota and CD8+ T cells shape the formation of invariant NKT cells.
AB  - Commensal bacteria play an important role in formation of the immune system, but
      the mechanisms involved are incompletely understood. In this study, we analyze
      CD1d-restricted invariant NKT (iNKT) cells in germfree mice and in two colonies
      of C57BL/6 mice termed conventional flora and restricted flora (RF), stably
      bearing commensal microbial communities of diverse but distinct composition. In
      germfree mice, iNKT cells were moderately reduced, suggesting that commensal
      microbiota were partially required for the antigenic drive in maintaining
      systemic iNKT cells. Surprisingly, even greater depletion of iNKT cell population
      occurred in RF mice. This was in part attributable to reduced RF levels of
      intestinal microbial taxa (Sphingomonas spp.) known to express antigenic
      glycosphingolipid products. However, memory and activated CD8(+) T cells were
      also expanded in RF mice, prompting us to test whether CD8(+) T cell activity
      might be further depleting iNKT cells. Indeed, iNKT cell numbers were restored in
      RF mice bearing the CD8alpha(-/-) genotype or in adult wild-type RF mice acutely
      depleted with anti-CD8 Ab. Moreover, iNKT cells were restored in RF mice bearing
      the Prf1(-/-) phenotype, a key component of cytolytic function. These findings
      indicate that commensal microbiota, through positive (antigenic drive) and
      negative (cytolytic depletion by CD8(+) T cells) mechanisms, profoundly shape the
      iNKT cell compartment. Because individuals greatly vary in the composition of
      their microbial communities, enteric microbiota may play an important epigenetic
      role in the striking differences in iNKT cell abundance in humans and therefore
      in their potential contribution to host immune status.

PMID- 20048126
TI  - Does the relationship between neighborhood socioeconomic status and health
      outcomes persist into very old age? A population-based study.
AB  - OBJECTIVE: The purpose of this article is (a) to extend previous research on the
      relationship between neighborhood socioeconomic status (SES) and health by
      considering a wide range of health-related measures derived from administrative
      health care records and (b) to explore whether this relationship persists into
      old age. METHOD: The study involved a complete cohort of community-dwelling
      residents in Winnipeg, Canada, who were 65 years or older in 2004/2005 (N =
      77,930). Health measures were derived from administrative claims data. Census
      data were used to derive neighborhood-level SES. RESULTS: Multilevel logistic
      regressions indicated that, relative to individuals living in the most affluent
      areas, those in the poorest areas had significantly higher odds of having
      arthritis, diabetes, hypertension, congestive heart failure, ischemic heart
      disease, chronic obstructive pulmonary disease, depression, and stroke.
      Significant neighborhood income effects tended to be evident among individuals
      age 65 to 75 as well as those age 75+. DISCUSSION: A wide range of health
      conditions among older adults are disproportionately clustered into the poorest
      areas. Programs and services should be designed to meet the needs of older adults
      of any age in such neighborhoods.

PMID- 20048132
TI  - The flu in retrospect: etiology and immunization.

PMID- 20048131
TI  - (124)I-iodopyridopyrimidinone for PET of Abl kinase-expressing tumors in vivo.
AB  - Because of the recent development of an iodopyridopyrimidinone Abl protein kinase
      inhibitor (PKI), (124)I-SKI-212230 ((124)I-SKI230), we investigated the
      feasibility of a PET-based molecular imaging method for the direct visualization
      of Abl kinase expression and PKI treatment. METHODS: In vitro pharmacokinetic
      properties, including specific and nonspecific binding of (124)I-SKI230 to its
      Abl kinase target and interaction with other PKIs, were assessed in cell-free
      medium and chronic myelogenous leukemia (CML) cells overexpressing BCR-Abl
      (K562), in comparison with BT-474 cells that are low in Abl expression. In a
      xenograft tumor model, we assessed the in vivo pharmacokinetics of (124)I-SKI230
      using PET and postmortem tissue sampling. We also tested a paradigm of (124)I
      SKI230 PET after treatment of the animal with a dose of Abl-specific PKI for the
      monitoring of the tumor response. RESULTS: In vitro studies confirmed that SKI230
      binds to Abl kinase with nanomolar affinity, that selective uptake occurs in cell
      lines known to express Abl kinase, that RNAi knock-down supports specificity of
      cellular uptake due to Abl kinase, and that imatinib, an archetype Abl PKI,
      completely displaces SKI230. With SKI230, we obtained successful in vivo PET of
      Abl-expressing human tumors in a nude rat. We were also able to demonstrate
      evidence of substrate inhibition of in vivo radiotracer uptake in the xenograft
      tumor after treatment of the animal as a model of PKI treatment monitoring.
      CONCLUSION: These results support the hypothesis that molecular imaging using PET
      will be useful for the study of in vivo pharmacodynamics of Abl PKI molecular
      therapy in humans.

PMID- 20048133
TI  - Therapeutic windows.

PMID- 20048134
TI  - Tumor-associated, estrogen receptor-related antigen EBAG9: linking intracellular
      vesicle trafficking, immune homeostasis, and malignancy.

PMID- 20048135
TI  - Wishing away inflammation? New links between serotonin and TNF signaling.

PMID- 20048136
TI  - Translational neuroimaging of the CNS: novel pathways to drug development.
AB  - Scientists engaged in drug discovery and development face many critical issues
      along the road to identifying the best drug candidates to bring forward for
      testing in patients. In neuroscience, these challenges can involve particularly
      demanding questions regarding target engagement, the predict ability of endpoints
      in animal models, new disease model validation, CNS penetration, and the
      identification of pharmacodynamic markers. For neurological conditions such as
      Alzheimer's disease, clinical trials of novel drugs that may modify the course of
      disease, rather than targeting specific symptoms, add extra layers of complexity.
      Major studies designed to track the course of a disease increasingly depend on
      noninvasive, translational imaging. In this brief review, we highlight examples
      of the new wave of neuroimaging studies that engender useful biomarkers of
      disease for translational research.

PMID- 20048138
TI  - A storied recipe for success, infused with basil.

PMID- 20048137
TI  - PHD fingers: epigenetic effectors and potential drug targets.
AB  - The plant homeodomain (PHD) finger is found in many chromatin-remodeling
      proteins. This small approximately 65-residue domain functions as an "effector"
      that binds specific epigenetic marks on histone tails, recruiting transcription
      factors and nucleosome-associated complexes to chromatin. Mutations in the PHD
      finger or deletion of this domain are linked to a number of human diseases,
      including cancer, mental retardation, and immunodeficiency. PHD finger-containing
      proteins may become valuable diagnostic markers and targets to prevent and treat
      these disorders. In this review, we highlight the progress recently made in
      understanding the functional significance of chromatin targeting by mammalian PHD
      fingers, detail the molecular mechanisms and structural features of "histone
      code" recognition, and discuss the therapeutic potential of PHD fingers.

PMID- 20048139
TI  - Intracranial dural sinus thrombosis: novel use of a mechanical thrombectomy
      catheter and review of management strategies.
AB  - Management of intracranial dural sinus thrombosis with involvement of multiple
      sinuses is complex, often involving not only the primary problem (thrombosis) but
      acute adverse events consequent to the disease. We highlight the novel use of an
      endovascular device (typically for suction thrombectomy in the peripheral
      vascular system) used in our patient with a life-threatening multi-sinus
      thrombosis. As there is no standard treatment yet for cranial sinus thrombosis,
      our review of the literature highlights some effective management strategies. A
      35-year-old woman developed associated complications of cranial sinus thrombosis
      that included intracranial hypertension caused by an expanding intracranial
      hematoma, pulmonary embolism treated by placement of filters in superior and
      inferior vena cava to eliminate intra- and extracranial sources of emboli, and
      procedure-related retroperitoneal hematoma that necessitated peripheral vascular
      intervention. After failure of several common devices during mechanical
      thrombolysis, a thrombectomy catheter (typically for peripheral vascular
      intervention to aide in the clot removal) was used. Our case highlights the fine
      balance of anticoagulation and thrombolysis and the proactive, aggressive
      approach used by our multispecialty team to manage concurrent factors.

PMID- 20048140
TI  - Unusual cases of multiple symmetrical lipomatosis with neurological disorders.
AB  - Multiple symmetrical lipomatosis (MSL) is a rare disorder of unknown etiology
      defined as the presence of multiple and symmetrical fatty accumulations, usually
      involving the upper trunk, neck and head. Frequently associated findings include
      diabetes mellitus, hyperlipidemia, liver disease, hypothyroidism and
      polyneuropathy of unknown origin, but nevertheless, there are published reports
      of cognitive disorders in patients with MSL. We describe two unusual cases (38
      year-old and 45-year-old Greek men) of MSL who presented with polyneuropathy and
      memory disorders. This is the first description of memory disorders in patients
      with MSL. We propose that Mini-Mental State Examination and assessment of
      cognitive functions should be performed for all patients with MSL. The underlying
      mechanism in our patients remains unknown, and this question should be the
      subject of a future study.

PMID- 20048141
TI  - Severe hydronephrosis in nephrogenic diabetes insipidus.

PMID- 20048145
TI  - p90 ribosomal S6 kinase 1 (RSK1) and the catalytic subunit of protein kinase A
      (PKA) compete for binding the pseudosubstrate region of PKAR1alpha: role in the
      regulation of PKA and RSK1 activities.
AB  - Previously we showed that the inactive form of p90 ribosomal S6 kinase 1 (RSK1)
      interacts with the regulatory subunit, PKARIalpha, of protein kinase A (PKA),
      whereas the active RSK1 interacts with the catalytic subunit (PKAc) of PKA.
      Herein, we demonstrate that the N-terminal kinase domain (NTK) of RSK1 is
      necessary for interactions with PKARIalpha. Substitution of the activation loop
      phosphorylation site (Ser-221) in the NTK with the negatively charged Asp residue
      abrogated the association between RSK1 and PKARIalpha. This explains the lack of
      an interaction between active RSK1 and PKARIalpha. Full-length RSK1 bound to
      PKARIalpha with an affinity of 0.8 nm. The NTK domain of RSK1 competed with PKAc
      for binding to the pseudosubstrate region (amino acids 93-99) of PKARIalpha.
      Overexpressed RSK1 dissociated PKAc from PKARIalpha, increasing PKAc activity,
      whereas silencing of RSK1 increased PKAc/PKARIalpha interactions and decreased
      PKAc activity. Unlike PKAc, which requires Arg-95 and -96 in the pseudosubstrate
      region of PKARIalpha for their interactions, RSK1/PKARIalpha association requires
      all four Arg residues (Arg-93-96) in the pseudosubstrate site of PKARIalpha. A
      peptide (Wt-PS) corresponding to residues 91-99 of PKARIalpha competed for
      binding of RSK1 with PKARIalpha both in vitro and in intact cells. Furthermore,
      peptide Wt-PS (but not control peptide Mut-PS), by dissociating RSK1 from
      PKARIalpha, activated RSK1 in the absence of any growth factors and protected
      cells from apoptosis. Thus, by competing for binding to the pseudosubstrate
      region of PKARIalpha, RSK1 regulates PKAc activity in a cAMP-independent manner,
      and PKARIalpha by associating with RSK1 regulates its activation and its
      biological functions.

PMID- 20048146
TI  - Inhibition of protein kinase Akt1 by apoptosis signal-regulating kinase-1 (ASK1)
      is involved in apoptotic inhibition of regulatory volume increase.
AB  - Most animal cell types regulate their cell volume after an osmotic volume change.
      The regulatory volume increase (RVI) occurs through uptake of NaCl and
      osmotically obliged water after osmotic shrinkage. However, apoptotic cells
      undergo persistent cell shrinkage without showing signs of RVI. Persistence of
      the apoptotic volume decrease is a prerequisite to apoptosis induction. We
      previously demonstrated that volume regulation is inhibited in human epithelial
      HeLa cells stimulated with the apoptosis inducer. Here, we studied signaling
      mechanisms underlying the apoptotic inhibition of RVI in HeLa cells. Hypertonic
      stimulation was found to induce phosphorylation of a Ser/Thr protein kinase Akt
      (protein kinase B). Shrinkage-induced Akt activation was essential for RVI
      induction because RVI was suppressed by an Akt inhibitor, expression of a
      dominant negative form of Akt, or small interfering RNA-mediated knockdown of
      Akt1 (but not Akt2). Staurosporine, tumor necrosis factor-alpha, or a Fas ligand
      inhibited both RVI and hypertonicity-induced Akt activation in a manner sensitive
      to a scavenger for reactive oxygen species (ROS). Any of apoptosis inducers also
      induced phosphorylation of apoptosis signal-regulating kinase 1 (ASK1) in a ROS
      dependent manner. Suppression of (ASK1) expression blocked the effects of
      apoptosis, in hypertonic conditions, on both RVI induction and Akt activation.
      Thus, it is concluded that in human epithelial cells, shrinkage-induced
      activation of Akt1 is involved in the RVI process and that apoptotic inhibition
      of RVI is caused by inhibition of Akt activation, which results from ROS-mediated
      activation of ASK1.

PMID- 20048147
TI  - Viral induction of the zinc finger antiviral protein is IRF3-dependent but NF
      kappaB-independent.
AB  - The zinc finger antiviral protein (ZAP) is an interferon-stimulated gene that
      restricts the replication of retroviruses, alphaviruses, and filoviruses.
      Relatively little is known, however, regarding the detailed mechanism of ZAP
      induction during viral infections. We show that, although being inducible by
      either interferon or virus, expression of ZAP is more efficiently activated by
      virus than are several other classical interferon-stimulated genes and that viral
      induction of ZAP occurs under the direct control of interferon regulatory factor
      3 (IRF3) independent of interferon paracrine/autocrine signaling. ZAP was up
      regulated in cells unresponsive to type I and III interferons upon engagement of
      TLR3, retinoic inducible gene I/melanoma differentiation-associated gene 5
      pathways, or ectopic expression of a constitutively active IRF3 mutant.
      Conversely, induction of ZAP by virus or dsRNA was severely impaired in cells
      expressing a dominant-negative mutant IRF3 and completely abrogated in cells
      lacking IRF3. In contrast to IRF3, ZAP induction was independent of NF-kappaB
      activity. Mutational analysis of the human ZAP promoter revealed that multiple
      interferon-stimulated response elements far distal to the transcription start
      site serve redundantly to control IRF3-dependent induction of ZAP transcription.
      Chromatin immunoprecipitation assays demonstrated that IRF3 selectively binds the
      distal interferon-stimulated response elements in human ZAP promoter following
      viral infection. Collectively, these data suggest that ZAP is a direct target
      gene of IRF3 action in cellular antiviral responses.

PMID- 20048149
TI  - Rheb GTPase controls apoptosis by regulating interaction of FKBP38 with Bcl-2 and
      Bcl-XL.
AB  - FKBP38 is a member of the family of FK506-binding proteins that acts as an
      inhibitor of the mammalian target of rapamycin (mTOR). The inhibitory action of
      FKBP38 is antagonized by Rheb, an oncogenic small GTPase, which interacts with
      FKBP38 and prevents its association with mTOR. In addition to the role in mTOR
      regulation, FKBP38 is also involved in binding and recruiting Bcl-2 and Bcl-X(L),
      two anti-apoptotic proteins, to mitochondria. In this study, we investigated the
      possibility that Rheb controls apoptosis by regulating the interaction of FKBP38
      with Bcl-2 and Bcl-X(L). We demonstrate in vitro that the interaction of FKBP38
      with Bcl-2 is regulated by Rheb in a GTP-dependent manner. In cultured cells, the
      interaction is controlled by Rheb in response to changes in amino acid and growth
      factor conditions. Importantly, we found that the Rheb-dependent release of Bcl
      X(L) from FKBP38 facilitates the association of this anti-apoptotic protein with
      the pro-apoptotic protein Bak. Consequently, when Rheb activity increases, cells
      become more resistant to apoptotic inducers. Our findings reveal a novel
      mechanism through which growth factors and amino acids control apoptosis.

PMID- 20048148
TI  - Lysyl oxidase propeptide inhibits FGF-2-induced signaling and proliferation of
      osteoblasts.
AB  - Pro-lysyl oxidase is secreted as a 50-kDa proenzyme and is then cleaved to a 30
      kDa mature enzyme (lysyl oxidase (LOX)) and an 18-kDa propeptide (lysyl oxidase
      propeptide (LOX-PP)). The presence of LOX-PP in the cell layers of phenotypically
      normal osteoblast cultures led us to investigate the effects of LOX-PP on
      osteoblast differentiation. Data indicate that LOX-PP inhibits terminal
      mineralization in primary calvaria osteoblast cultures when added at early stages
      of differentiation, with no effects seen when present at later stages. LOX-PP was
      found to inhibit serum- and FGF-2-stimulated DNA synthesis and FGF-2-stimulated
      cell growth. Enzyme-linked immunosorbent assay and Western blot analyses show
      that LOX-PP inhibits FGF-2-induced ERK1/2 phosphorylation, signaling events that
      mediate the FGF-2-induced proliferative response. LOX-PP inhibits FGF-2
      stimulated phosphorylation of FRS2alpha and FGF-2-stimulated DNA synthesis, even
      after inhibition of sulfation of heparan sulfate proteoglycans. These data point
      to a LOX-PP target at or near the level of fibroblast growth factor receptor
      binding or activation. Ligand binding assays on osteoblast cell layers with
      (125)I-FGF-2 demonstrate a concentration-dependent inhibition of FGF-2 binding to
      osteoblasts by LOX-PP. In vitro binding assays with recombinant fibroblast growth
      factor receptor protein revealed that LOX-PP inhibits FGF-2 binding in an
      uncompetitive manner. We propose a working model for the respective roles of LOX
      enzyme and LOX-PP in osteoblast phenotype development in which LOX-PP may act to
      inhibit the proliferative response possibly to allow cells to exit from the cell
      cycle and progress to the next stages of differentiation.

PMID- 20048150
TI  - Identification of a key residue mediating bone morphogenetic protein (BMP)-6
      resistance to noggin inhibition allows for engineered BMPs with superior agonist
      activity.
AB  - Bone morphogenetic proteins (BMPs) are used clinically to induce new bone
      formation in spinal fusions and long bone non-union fractures. However, large
      amounts of BMPs are needed to achieve these effects. BMPs were found to increase
      the expression of antagonists, which potentially limit their therapeutic
      efficacy. However, the relative susceptibility of osteoinductive BMPs to
      different antagonists is not well characterized. Here we show that BMP-6 is more
      resistant to noggin inhibition and more potent in promoting osteoblast
      differentiation in vitro and inducing bone regeneration in vivo when compared
      with its closely related BMP-7 paralog. Noggin was found to play a critical role
      as a negative feedback regulator of BMP-7 but not BMP-6-induced biological
      responses. Using BMP-6/7 chimeras, we identified lysine 60 as a key residue
      conferring noggin resistance within the BMP-6 protein. A remarkable correlation
      was found between the presence of a lysine at this position and noggin resistance
      among a panel of osteoinductive BMPs. Introduction of a lysine residue at the
      corresponding positions of BMP-2 and BMP-7 allowed for molecular engineering of
      recombinant BMPs with increased resistance to noggin antagonism.

PMID- 20048151
TI  - Structural basis for acetylated histone H4 recognition by the human BRD2
      bromodomain.
AB  - Recognition of acetylated chromatin by the bromodomains and extra-terminal domain
      (BET) family proteins is a hallmark for transcriptional activation and anchoring
      viral genomes to mitotic chromosomes of the host. One of the BET family proteins
      BRD2 interacts with acetylated chromatin during mitosis and leads to
      transcriptional activation in culture cells. Here, we report the crystal
      structures of the N-terminal bromodomain of human BRD2 (BRD2-BD1; residues 74
      194) in complex with each of three different Lys-12-acetylated H4 peptides. The
      BRD2-BD1 recognizes the H4 tail acetylated at Lys-12 (H4K12ac), whereas the side
      chain of hypoacetylated Lys-8 of H4 binds at the cavity of the dimer interface of
      BRD2-BD1. From binding studies, we identified the BRD2-BD1 residues that are
      responsible for recognition of the Lys-12-acetylated H4 tail. In addition,
      mutation to Lys-8 in the Lys-12-acetylated H4 tail decreased the binding to BRD2
      BD1, implicating the critical role of Lys-8 in the Lys-12-acetylated H4 tail for
      the recognition by BRD2-BD1. Our findings provide a structural basis for
      deciphering the histone code by the BET bromodomain through the binding with a
      long segment of the histone H4 tail, which presumably prevents erasure of the
      histone code during the cell cycle.

PMID- 20048152
TI  - p66shc inhibits insulin-like growth factor-I signaling via direct binding to Src
      through its polyproline and Src homology 2 domains, resulting in impairment of
      Src kinase activation.
AB  - p66(shc) is increased in response to cell stress, and these increases regulate
      growth factor actions. These studies were conducted to determine how p66(shc)
      alters IGF-I-stimulated Src activation, leading to decreased IGF-I actions. Our
      results show that p66(shc) binds to Src through a polyproline sequence motif
      contained in the CH2 domain, a unique domain in p66(shc), and IGF-I stimulates
      this interaction. Disruption of this interaction using a synthetic peptide
      containing the p66(shc) polyproline domain or expression of a p66(shc) mutant
      containing substitutions for the proline residues (P47A/P48A/P50A) resulted in
      enhanced Src kinase activity, p52(shc) phosphorylation, MAPK activation, and cell
      proliferation in response to IGF-I. To determine the mechanism of inhibition, the
      full-length CH2 domain and intact p66(shc) were tested for their ability to
      directly inhibit Src kinase activation in vitro. The CH2 domain peptide was
      clearly inhibitory, but full-length p66(shc) had a greater effect. Deletion of
      the C-terminal Src homology 2 domain in p66(shc) reduced its ability to inhibit
      Src kinase activation. These findings demonstrate that p66(shc) utilizes a novel
      mechanism for modulating Src kinase activation and that this interaction is
      mediated through both its collagen homologous region 2 and Src homology 2
      domains.

PMID- 20048153
TI  - Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple
      kinases and results in differential modulation of CXCR4 signaling.
AB  - The chemokine receptor CXCR4 is a widely expressed G protein-coupled receptor
      that has been implicated in a number of diseases including human immunodeficiency
      virus, cancer, and WHIM syndrome, with the latter two involving dysregulation of
      CXCR4 signaling. To better understand the role of phosphorylation in regulating
      CXCR4 signaling, tandem mass spectrometry and phospho-specific antibodies were
      used to identify sites of agonist-promoted phosphorylation. These studies
      demonstrated that Ser-321, Ser-324, Ser-325, Ser-330, Ser-339, and two sites
      between Ser-346 and Ser-352 were phosphorylated in HEK293 cells. We show that Ser
      324/5 was rapidly phosphorylated by protein kinase C and G protein-coupled
      receptor kinase 6 (GRK6) upon CXCL12 treatment, whereas Ser-339 was specifically
      and rapidly phosphorylated by GRK6. Ser-330 was also phosphorylated by GRK6,
      albeit with slower kinetics. Similar results were observed in human astroglia
      cells, where endogenous CXCR4 was rapidly phosphorylated on Ser-324/5 by protein
      kinase C after CXCL12 treatment, whereas Ser-330 was slowly phosphorylated.
      Analysis of CXCR4 signaling in HEK293 cells revealed that calcium mobilization
      was primarily negatively regulated by GRK2, GRK6, and arrestin3, whereas GRK3,
      GRK6, and arrestin2 played a primary role in positively regulating ERK1/2
      activation. In contrast, GRK2 appeared to play a negative role in ERK1/2
      activation. Finally, we show that arrestin association with CXCR4 is primarily
      driven by the phosphorylation of far C-terminal residues on the receptor. These
      studies reveal that site-specific phosphorylation of CXCR4 is dynamically
      regulated by multiple kinases resulting in both positive and negative modulation
      of CXCR4 signaling.

PMID- 20048154
TI  - Zinc-induced neurotoxicity mediated by transient receptor potential melastatin 7
      channels.
AB  - Transient receptor potential melastatin 7 (TRPM7) channels are novel Ca(2+)
      permeable non-selective cation channels ubiquitously expressed. Activation of
      TRPM7 channels has been shown to be involved in cellular Mg(2+) homeostasis,
      diseases caused by abnormal magnesium absorption, and in Ca(2+)-mediated neuronal
      injury under ischemic conditions. Here we show strong evidence suggesting that
      TRPM7 channels also play an important role in cellular Zn(2+) homeostasis and in
      Zn(2+)-mediated neuronal injury. Using a combination of fluorescent Zn(2+)
      imaging, small interfering RNA, pharmacological analysis, and cell injury assays,
      we show that activation of TRPM7 channels augmented Zn(2+)-induced injury of
      cultured mouse cortical neurons. The Zn(2+)-mediated neurotoxicity was inhibited
      by nonspecific TRPM7 blockers Gd(3+) or 2-aminoethoxydiphenyl borate, and by
      knockdown of TRPM7 channels with small interfering RNA. In addition, Zn(2+)
      mediated neuronal injury under oxygen-glucose deprivation conditions was also
      diminished by silencing TRPM7. Furthermore, we show that overexpression of TRPM7
      channels in HEK293 cells increased intracellular Zn(2+) accumulation and Zn(2+)
      induced cell injury, while silencing TRPM7 by small interfering RNA attenuated
      the Zn(2+)-mediated cell toxicity. Thus, TRPM7 channels may represent a novel
      target for neurological disorders where Zn(2+) toxicity plays an important role.

PMID- 20048156
TI  - Coordination of hepatocyte nuclear factor 4 and seven-up controls insect counter
      defense cathepsin B expression.
AB  - CmCatB, a cathepsin B-type cysteine protease, is insensitive to inhibition by the
      soybean cysteine protease inhibitor (scN). Cowpea bruchids dramatically induce
      CmCatB expression when major digestive proteases are inactivated by dietary scN,
      which is presumably an adaptive strategy that insects use to minimize effects of
      nutrient deficiency. In this study, we cloned the cowpea bruchid hepatocyte
      nuclear factor 4 (CmHNF-4) and demonstrated its involvement in transcriptional
      activation of CmCatB in the digestive tract of scN-adapted bruchids.
      Electrophoretic mobility shift assays demonstrated that CmHNF-4 binds to a CmCatB
      promoter region containing two tandem chicken ovalbumin upstream promoter (COUP)
      sites, which is also the cis-element for Seven-up (CmSvp), a previously
      identified transcriptional repressor of CmCatB. Although CmSvp is predominantly
      expressed in unadapted insect midgut, CmHNF-4 is more abundant in adapted
      bruchids. When transiently expressed in Drosophila S2 cells, CmHNF-4
      substantially increased CmCatB expression through COUP binding. CmSvp inhibited
      CmHNF-4-mediated transcriptional activation even in the absence of its DNA
      binding domain. Thus antagonism resulted, at least in part, from protein-protein
      interactions between CmSvp and CmHNF-4. Association of the two transcription
      factors was subsequently confirmed by glutathione S-transferase pulldown assays.
      Interestingly, anti-CmHNF-4 serum caused a supershift not only with nuclear
      extracts of scN-adapted insect midgut but with that of unadapted control insects
      as well. The presence of CmHNF-4 in unadapted insects further supported the idea
      that interplay between CmSvp and CmHNF-4 controls CmCatB transcription
      activation. Together, these results suggest that coordination between CmHNF-4 and
      CmSvp is important in counter-defense gene regulation in insects.

PMID- 20048155
TI  - Withaferin A targets intermediate filaments glial fibrillary acidic protein and
      vimentin in a model of retinal gliosis.
AB  - Gliosis is a biological process that occurs during injury repair in the central
      nervous system and is characterized by the overexpression of the intermediate
      filaments (IFs) glial fibrillary acidic protein (GFAP) and vimentin. A common
      thread in many retinal diseases is reactive Muller cell gliosis, an untreatable
      condition that leads to tissue scarring and even blindness. Here, we demonstrate
      that the vimentin-targeting small molecule withaferin A (WFA) is a novel chemical
      probe of GFAP. Using molecular modeling studies that build on the x-ray crystal
      structure of tetrameric vimentin rod 2B domain we reveal that the WFA binding
      site is conserved in the corresponding domain of tetrameric GFAP. Consequently,
      we demonstrate that WFA covalently binds soluble recombinant tetrameric human
      GFAP at cysteine 294. In cultured primary astrocytes, WFA binds to and down
      regulates soluble vimentin and GFAP expression to cause cell cycle G(0)/G(1)
      arrest. Exploiting a chemical injury model that overexpresses vimentin and GFAP
      in retinal Muller glia, we demonstrate that systemic delivery of WFA down
      regulates soluble vimentin and GFAP expression in mouse retinas. This
      pharmacological knockdown of soluble IFs results in the impairment of GFAP
      filament assembly and inhibition of cell proliferative response in Muller glia.
      We further show that a more severe GFAP filament assembly deficit manifests in
      vimentin-deficient mice, which is partly rescued by WFA. These findings
      illustrate WFA as a chemical probe of type III IFs and illuminate this class of
      withanolide as a potential treatment for diverse gliosis-dependent central
      nervous system traumatic injury conditions and diseases, and for orphan IF
      dependent pathologies.

PMID- 20048157
TI  - Alpha2,6-sialic acid on platelet endothelial cell adhesion molecule (PECAM)
      regulates its homophilic interactions and downstream antiapoptotic signaling.
AB  - Antiangiogenesis therapies are now part of the standard repertoire of cancer
      therapies, but the mechanisms for the proliferation and survival of endothelial
      cells are not fully understood. Although endothelial cells are covered with a
      glycocalyx, little is known about how endothelial glycosylation regulates
      endothelial functions. Here, we show that alpha2,6-sialic acid is necessary for
      the cell-surface residency of platelet endothelial cell adhesion molecule
      (PECAM), a member of the immunoglobulin superfamily that plays multiple roles in
      cell adhesion, mechanical stress sensing, antiapoptosis, and angiogenesis. As a
      possible underlying mechanism, we found that the homophilic interactions of PECAM
      in endothelial cells were dependent on alpha2,6-sialic acid. We also found that
      the absence of alpha2,6-sialic acid down-regulated the tyrosine phosphorylation
      of PECAM and recruitment of Src homology 2 domain-containing protein-tyrosine
      phosphatase 2 and rendered the cells more prone to mitochondrion-dependent
      apoptosis, as evaluated using PECAM- deficient endothelial cells. The present
      findings open up a new possibility that modulation of glycosylation could be one
      of the promising strategies for regulating angiogenesis.

PMID- 20048158
TI  - Mutations in Lama1 disrupt retinal vascular development and inner limiting
      membrane formation.
AB  - The Neuromutagenesis Facility at the Jackson Laboratory generated a mouse model
      of retinal vasculopathy, nmf223, which is characterized clinically by vitreal
      fibroplasia and vessel tortuosity. nmf223 homozygotes also have reduced
      electroretinogram responses, which are coupled histologically with a thinning of
      the inner nuclear layer. The nmf223 locus was mapped to chromosome 17, and a
      missense mutation was identified in Lama1 that leads to the substitution of
      cysteine for a tyrosine at amino acid 265 of laminin alpha1, a basement membrane
      protein. Despite normal localization of laminin alpha1 and other components of
      the inner limiting membrane, a reduced integrity of this structure was suggested
      by ectopic cells and blood vessels within the vitreous. Immunohistochemical
      characterization of nmf223 homozygous retinas demonstrated the abnormal migration
      of retinal astrocytes into the vitreous along with the persistence of hyaloid
      vasculature. The Y265C mutation significantly reduced laminin N-terminal domain
      (LN) interactions in a bacterial two-hybrid system. Therefore, this mutation
      could affect interactions between laminin alpha1 and other laminin chains. To
      expand upon these findings, a Lama1 null mutant, Lama1(tm1.1Olf), was generated
      that exhibits a similar but more severe retinal phenotype than that seen in
      nmf223 homozygotes. The increased severity of the Lama1 null mutant phenotype is
      probably due to the complete loss of the inner limiting membrane in these mice.
      This first report of viable Lama1 mouse mutants emphasizes the importance of this
      gene in retinal development. The data presented herein suggest that hypomorphic
      mutations in human LAMA1 could lead to retinal disease.

PMID- 20048159
TI  - Assembly of the biogenesis of lysosome-related organelles complex-3 (BLOC-3) and
      its interaction with Rab9.
AB  - The Hermansky-Pudlak syndrome (HPS) is a genetic hypopigmentation and bleeding
      disorder caused by defective biogenesis of lysosome-related organelles (LROs)
      such as melanosomes and platelet dense bodies. HPS arises from mutations in any
      of 8 genes in humans and 16 genes in mice. Two of these genes, HPS1 and HPS4,
      encode components of the biogenesis of lysosome-related organelles complex-3
      (BLOC-3). Herein we show that recombinant HPS1-HPS4 produced in insect cells can
      be efficiently isolated as a 1:1 heterodimer. Analytical ultracentrifugation
      reveals that this complex has a molecular mass of 146 kDa, equivalent to that of
      the native complex and to the sum of the predicted molecular masses of HPS1 and
      HPS4. This indicates that HPS1 and HPS4 interact directly in the absence of any
      other protein as part of BLOC-3. Limited proteolysis and deletion analyses show
      that both subunits interact with one another throughout most of their lengths
      with the sole exception of a long, unstructured loop in the central part of HPS4.
      An interaction screen reveals a specific and strong interaction of BLOC-3 with
      the GTP-bound form of the endosomal GTPase, Rab9. This interaction is mediated by
      HPS4 and the switch I and II regions of Rab9. These characteristics indicate that
      BLOC-3 might function as a Rab9 effector in the biogenesis of LROs.

PMID- 20048160
TI  - Androgen receptor-dependent transactivation of growth arrest-specific gene 6
      mediates inhibitory effects of testosterone on vascular calcification.
AB  - Recent epidemiological studies have found that androgen deficiency is associated
      with a higher incidence of cardiovascular disease in men. However, little is
      known about the mechanism underlying the cardioprotective effects of androgens.
      Here we show the inhibitory effects of testosterone on vascular calcification and
      a critical role of androgen receptor (AR)-dependent transactivation of growth
      arrest-specific gene 6 (Gas6), a key regulator of inorganic phosphate (P(i))
      induced calcification of vascular smooth muscle cells (VSMC). Testosterone and
      nonaromatizable androgen dihydrotestosterone inhibited P(i)-induced calcification
      of human aortic VSMC in a concentration-dependent manner. Androgen inhibited P(i)
      induced VSMC apoptosis, an essential process for VSMC calcification. The effects
      on VSMC calcification were mediated by restoration of P(i)-induced down
      regulation of Gas6 expression and a subsequent reduction of Akt phosphorylation.
      These effects of androgen were blocked by an AR antagonist, flutamide, but not by
      an estrogen receptor antagonist, ICI 182,780. We then explored the mechanistic
      role of the AR in Gas6 expression and found an abundant expression of AR
      predominantly in the nucleus of VSMC and two consensus ARE sequences in the Gas6
      promoter region. Dihydrotestosterone stimulated Gas6 promoter activity, and this
      effect was abrogated by flutamide and by AR siRNA. Site-specific mutation
      revealed that the proximal ARE was essential for androgen-dependent
      transactivation of Gas6. Furthermore, chromatin immunoprecipitation assays
      demonstrated ligand-dependent binding of the AR to the proximal ARE of Gas6.
      These results indicate that AR signaling directly regulates Gas6 transcription,
      which leads to inhibition of vascular calcification, and provides a mechanistic
      insight into the cardioprotective action of androgens.

PMID- 20048161
TI  - Proteoliposomes harboring alkaline phosphatase and nucleotide pyrophosphatase as
      matrix vesicle biomimetics.
AB  - We have established a proteoliposome system as an osteoblast-derived matrix
      vesicle (MV) biomimetic to facilitate the study of the interplay of tissue
      nonspecific alkaline phosphatase (TNAP) and NPP1 (nucleotide
      pyrophosphatase/phosphodiesterase-1) during catalysis of biomineralization
      substrates. First, we studied the incorporation of TNAP into liposomes of various
      lipid compositions (i.e. in pure dipalmitoyl phosphatidylcholine (DPPC),
      DPPC/dipalmitoyl phosphatidylserine (9:1 and 8:2), and DPPC/dioctadecyl
      dimethylammonium bromide (9:1 and 8:2) mixtures. TNAP reconstitution proved
      virtually complete in DPPC liposomes. Next, proteoliposomes containing either
      recombinant TNAP, recombinant NPP1, or both together were reconstituted in DPPC,
      and the hydrolysis of ATP, ADP, AMP, pyridoxal-5'-phosphate (PLP), p-nitrophenyl
      phosphate, p-nitrophenylthymidine 5'-monophosphate, and PP(i) by these
      proteoliposomes was studied at physiological pH. p-Nitrophenylthymidine 5'
      monophosphate and PLP were exclusively hydrolyzed by NPP1-containing and TNAP
      containing proteoliposomes, respectively. In contrast, ATP, ADP, AMP, PLP, p
      nitrophenyl phosphate, and PP(i) were hydrolyzed by TNAP-, NPP1-, and TNAP plus
      NPP1-containing proteoliposomes. NPP1 plus TNAP additively hydrolyzed ATP, but
      TNAP appeared more active in AMP formation than NPP1. Hydrolysis of PP(i) by TNAP
      , and TNAP plus NPP1-containing proteoliposomes occurred with catalytic
      efficiencies and mild cooperativity, effects comparable with those manifested by
      murine osteoblast-derived MVs. The reconstitution of TNAP and NPP1 into
      proteoliposome membranes generates a phospholipid microenvironment that allows
      the kinetic study of phosphosubstrate catabolism in a manner that recapitulates
      the native MV microenvironment.

PMID- 20048162
TI  - G protein betagamma subunits regulate cell adhesion through Rap1a and its
      effector Radil.
AB  - The activation of several G protein-coupled receptors is known to regulate the
      adhesive properties of cells in different contexts. Here, we reveal that
      Gbetagamma subunits of heterotrimeric G proteins regulate cell-matrix
      adhesiveness by activating Rap1a-dependent inside-out signals and integrin
      activation. We show that Gbetagamma subunits enter in a protein complex with
      activated Rap1a and its effector Radil and establish that this complex is
      required downstream of receptor stimulation for the activation of integrins and
      the positive modulation of cell-matrix adhesiveness. Moreover, we demonstrate
      that Gbetagamma and activated Rap1a promote the translocation of Radil to the
      plasma membrane at sites of cell-matrix contacts. These results add to the
      molecular understanding of how G protein-coupled receptors impinge on cell
      adhesion and suggest that the Gbetagamma x Rap1 x Radil complex plays important
      roles in this process.

PMID- 20048163
TI  - GADD45beta enhances Col10a1 transcription via the MTK1/MKK3/6/p38 axis and
      activation of C/EBPbeta-TAD4 in terminally differentiating chondrocytes.
AB  - GADD45beta (growth arrest- and DNA damage-inducible) interacts with upstream
      regulators of the JNK and p38 stress response kinases. Previously, we reported
      that the hypertrophic zone of the Gadd45beta(-/-) mouse embryonic growth plate is
      compressed, and expression of type X collagen (Col10a1) and matrix
      metalloproteinase 13 (Mmp13) genes is decreased. Herein, we report that
      GADD45beta enhances activity of the proximal Col10a1 promoter, which contains
      evolutionarily conserved AP-1, cAMP-response element, and C/EBP half-sites, in
      synergism with C/EBP family members, whereas the MMP13 promoter responds to
      GADD45beta together with AP-1, ATF, or C/EBP family members. C/EBPbeta expression
      also predominantly co-localizes with GADD45beta in the embryonic growth plate.
      Moreover, GADD45beta enhances C/EBPbeta activation via MTK1, MKK3, and MKK6, and
      dominant-negative p38alphaapf, but not JNKapf, disrupts the combined trans
      activating effect of GADD45beta and C/EBPbeta on the Col10a1 promoter.
      Importantly, GADD45beta knockdown prevents p38 phosphorylation while decreasing
      Col10a1 mRNA levels but does not affect C/EBPbeta binding to the Col10a1 promoter
      in vivo, indicating that GADD45beta influences the transactivation function of
      DNA-bound C/EBPbeta. In support of this conclusion, we show that the
      evolutionarily conserved TAD4 domain of C/EBPbeta is the target of the GADD45beta
      dependent signaling. Collectively, we have uncovered a novel molecular mechanism
      linking GADD45beta via the MTK1/MKK3/6/p38 axis to C/EBPbeta-TAD4 activation of
      Col10a1 transcription in terminally differentiating chondrocytes.

PMID- 20048164
TI  - Plasminogen- and fibronectin-binding protein B is involved in the adherence of
      Streptococcus pneumoniae to human epithelial cells.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide.
      The ability of this bacterium to adhere to epithelial cells is considered as an
      essential early step in colonization and infection. By screening a whole genome
      phage display library with sera from infected patients, we previously identified
      three antigenic fragments matching open reading frame spr0075 of the strain R6
      genome. This locus encodes for an approximately 120-kDa protein, herein referred
      to as plasminogen- and fibronectin-binding protein B (PfbB), which displays an
      LPXTG cell wall anchoring motif and six repetitive domains. In this study, by
      using isogenic pfbB-deleted mutants of the encapsulated D39 and of the
      unencapsulated DP1004 type 2 pneumococcal strains, we show that PfbB is involved
      in S. pneumoniae adherence to various epithelial respiratory tract cell lines.
      Our data suggest that PfbB directly mediates bacterial adhesion, because
      fluorescent beads coated with the recombinant PfbB sp17 fragment (encompassing
      one of the six repetitive domains and the C-terminal region) efficiently bound to
      epithelial cells. Mutants lacking PfbB bound to fibronectin and plasminogen
      considerably less efficiently than wild type bacteria, whereas sp17-coated beads
      specifically bound to both of these substrates. Taken together, our data suggest
      that, by directly interacting with fibronectin, PfbB significantly increases the
      ability of S. pneumoniae to adhere to human epithelial cells.

PMID- 20048165
TI  - Saccharomyces cerevisiae Esc2p interacts with Sir2p through a small ubiquitin
      like modifier (SUMO)-binding motif and regulates transcriptionally silent
      chromatin in a locus-dependent manner.
AB  - Saccharomyces cerevisiae Esc2p is a member of a conserved family of proteins that
      contain small ubiquitin-like modifier (SUMO)-like domains. It has been implicated
      in transcriptional silencing and shown to interact with the silencing protein
      Sir2p in a two-hybrid analysis. However, little is known about how Esc2p
      regulates the structure of silent chromatin. We demonstrate here that ESC2
      differentially regulates silent chromatin at telomeric, rDNA, and HM loci.
      Specifically, ESC2 is required for efficient telomeric silencing and Sir2p
      association with telomeric silent chromatin and for silencing and maintenance of
      silent chromatin structure at rDNA. On the other hand, ESC2 negatively regulates
      silencing at HML and HMR and destabilizes HML silent chromatin without affecting
      Sir2p association with chromatin. We present evidence that Esc2p is associated
      with both transcriptionally silent and active loci in the genome, and the
      abundance of Esc2p is not correlated with the chromatin state at a particular
      locus. Using affinity pull-down analyses, we show that Esc2p and Sir2p interact
      in vivo, and recombinant Esc2p and Sir2p interact directly. Moreover, we dissect
      Esc2p and identify a putative SUMO-binding motif that is necessary and sufficient
      for interacting with Sir2p and SUMO and is required for the function of Esc2p in
      transcriptional silencing.

PMID- 20048166
TI  - Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen inhibits
      interferon (IFN) beta expression by competing with IFN regulatory factor-3 for
      binding to IFNB promoter.
AB  - Host cells respond to viral infections by synthesizing and producing antiviral
      molecules such as type I interferons (IFN). The Kaposi sarcoma-associated
      herpesvirus (KSHV) encodes multiple proteins expressed during the lytic
      replication cycle that alter the antiviral response of the host. Considering that
      in Kaposi sarcoma lesions and primary effusion lymphoma cells KSHV is latent in
      the vast majority of cells, we were interested in determining whether latently
      expressed viral proteins have the ability to modulate IFN synthesis. The latency
      associated nuclear antigen (LANA-1) is a large nuclear protein that plays a role
      in the establishment and maintenance of latent KSHV episome in the nucleus of
      infected cells. LANA-1 is also described to modulate the cellular transcription.
      Here, we report that LANA-1 inhibits IFN-beta transcription and synthesis by
      competing with the binding of interferon regulatory factor-3 (IRF3) to the IFNB
      promoter. Using mutants of LANA-1, we have identified the central acidic repeated
      region as the domain essential for interfering with the binding of IRF3 to the
      positive regulatory domains I-III of the IFNB promoter. In addition, the nuclear
      localization of LANA-1 proved essential for IFN-beta inhibition. Thus, LANA-1
      interferes with the formation of IFN-beta enhanceosome by competing with the
      fixation of IRF3 and by inhibiting the expression of the CREB-binding protein.
      The ability of LANA-1 to inhibit IFNB gene expression highlights a new role for
      this protein in cellular gene modulation and immune evasion strategies.

PMID- 20048167
TI  - Src-induced tyrosine phosphorylation of VE-cadherin is not sufficient to decrease
      barrier function of endothelial monolayers.
AB  - Activation of Src family kinases (SFK) and the subsequent phosphorylation of VE
      cadherin have been proposed as major regulatory steps leading to increases in
      vascular permeability in response to inflammatory mediators and growth factors.
      To investigate Src signaling in the absence of parallel signaling pathways
      initiated by growth factors or inflammatory mediators, we activated Src and SFKs
      by expression of dominant negative Csk, expression of constitutively active Src,
      or knockdown of Csk. Activation of SFK by overexpression of dominant negative Csk
      induced VE-cadherin phosphorylation at tyrosines 658, 685, and 731. However,
      dominant negative Csk expression was unable to induce changes in the monolayer
      permeability. In contrast, expression of constitutively active Src decreased
      barrier function and promoted VE-cadherin phosphorylation on tyrosines 658 and
      731, although the increase in VE-cadherin phosphorylation preceded the increase
      in permeability by 4-6 h. Csk knockdown induced VE-cadherin phosphorylation at
      sites 658 and 731 but did not induce a loss in barrier function. Co
      immunoprecipitation and immunofluorescence studies suggest that phosphorylation
      of those sites did not impair VE-cadherin ability to bind p120 and beta-catenin
      or the ability of these proteins to localize at the plasma membrane. Taken
      together, our data show that Src-induced tyrosine phosphorylation of VE-cadherin
      is not sufficient to promote an increase in endothelial cell monolayer
      permeability and suggest that signaling leading to changes in vascular
      permeability in response to inflammatory mediators or growth factors may require
      VE-cadherin tyrosine phosphorylation concurrently with other signaling pathways
      to promote loss of barrier function.

PMID- 20048168
TI  - RANKL-mediated reactive oxygen species pathway that induces long lasting Ca2+
      oscillations essential for osteoclastogenesis.
AB  - RANKL (receptor activator of NF-kappaB ligand) induces osteoclastogenesis by
      activating multiple signaling pathways in osteoclast precursor cells, chief among
      which is induction of long lasting oscillations in the intracellular
      concentration of Ca(2+) ([Ca(2+)](i)). The [Ca(2+)](i) oscillations activate
      calcineurin, which activates the transcription factor NFATc1. The pathway by
      which RANKL induces [Ca(2+)](i) oscillations and osteoclastogenesis is poorly
      understood. Here we report the discovery of a novel pathway induced by RANKL to
      cause a long lasting increase in reactive oxygen species (ROS) and [Ca(2+)](i)
      oscillations that is essential for differentiation of bone marrow-derived
      monocytes into osteoclasts. The pathway includes RANKL-mediated stimulation of
      Rac1 to generate ROS, which stimulate phospholipase Cgamma1 to evoke [Ca(2+)](i)
      oscillations by stimulating Ca(2+) release from the inositol 1,4,5-trisphosphate
      pool and STIM1-regulated Ca(2+) influx. Induction and activation of the pathway
      is observed only after 24-h stimulation with RANKL and lasts for at least 3 days.
      The physiological role of the pathway is demonstrated in mice with deletion of
      the Peroxiredoxin II gene and results in a mark increase is ROS and,
      consequently, a decrease in bone density. Moreover, bone marrow-derived monocytes
      in PrxII(-/-) primary culture show increased ROS and spontaneous [Ca(2+)](i)
      oscillations. These findings identify the primary RANKL-stimulated pathway to
      trigger the late stages of osteoclastogenesis and regulate bone resorption.

PMID- 20048169
TI  - Intra- and interdomain effects due to mutation of calcium-binding sites in
      calmodulin.
AB  - The IQ-motif protein PEP-19, binds to the C-domain of calmodulin (CaM) with
      significantly different k(on) and k(off) rates in the presence and absence of
      Ca(2+), which could play a role in defining the levels of free CaM during Ca(2+)
      transients. The initial goal of the current study was to determine whether Ca(2+)
      binding to sites III or IV in the C-domain of CaM was responsible for affecting
      the kinetics of binding PEP-19. EF-hand Ca(2+)-binding sites were selectively
      inactivated by the common strategy of changing Asp to Ala at the X-coordination
      position. Although Ca(2+) binding to both sites III and IV appeared necessary for
      native-like interactions with PEP-19, the data also indicated that the mutations
      caused undesirable structural alterations as evidenced by significant changes in
      amide chemical shifts for apoCaM. Mutations in the C-domain also affected
      chemical shifts in the unmodified N-domain, and altered the Ca(2+) binding
      properties of the N-domain. Conversion of Asp(93) to Ala caused the greatest
      structural perturbations, possibly due to the loss of stabilizing hydrogen bonds
      between the side chain of Asp(93) and backbone amides in apo loop III. Thus,
      although these mutations inhibit binding of Ca(2+), the mutated CaM may not be
      able to support potentially important native-like activity of the apoprotein.
      This should be taken into account when designing CaM mutants for expression in
      cell culture.

PMID- 20048170
TI  - Amiloride docking to acid-sensing ion channel-1.
AB  - Amiloride is a small molecule diuretic, which has been used to dissect sodium
      transport pathways in many different systems. This drug is known to interact with
      the epithelial sodium channel and acid-sensing ion channel proteins, as well as
      sodium/hydrogen antiporters and sodium/calcium exchangers. The exact structural
      basis for these interactions has not been elucidated as crystal structures of
      these proteins have been challenging to obtain, though some involved residues and
      domains have been mapped. This work examines the interaction of amiloride with
      acid-sensing ion channel-1, a protein whose structure is available using
      computational and experimental techniques. Using molecular docking software,
      amiloride and related molecules were docked to model structures of homomeric
      human ASIC-1 to generate potential interaction sites and predict which analogs
      would be more or less potent than amiloride. The predictions made were
      experimentally tested using whole-cell patch clamp. Drugs previously classified
      as NCX or NHE inhibitors are shown to also inhibit hASIC-1. Potential docking
      sites were re-examined against experimental data to remove spurious interaction
      sites. The voltage sensitivity of inhibitors was also examined. Using the
      aggregated data from these computational and experimental experiments, putative
      interaction sites for amiloride and hASIC-1 have been defined. Future work will
      experimentally verify these interaction sites, but at present this should allow
      for virtual screening of drug libraries at these putative interaction sites.

PMID- 20048171
TI  - Functional p53 status as a biomarker for chemotherapy response in oral-cavity
      cancer.

PMID- 20048173
TI  - Breast conservation treatment with radiation: an ongoing success story.

PMID- 20048172
TI  - Sirolimus and temsirolimus for epithelioid angiomyolipoma.

PMID- 20048175
TI  - Pulmonary calciphylaxis and metastatic calcification with acute respiratory
      failure in multiple myeloma.

PMID- 20048174
TI  - Clinical activity of mTOR inhibition with sirolimus in malignant perivascular
      epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors.
AB  - PURPOSE Perivascular epithelioid cell tumors (PEComas) represent a family of
      mesenchymal neoplasms, mechanistically linked through activation of the mTOR
      signaling pathway. There is no known effective therapy for PEComa, and the
      molecular pathophysiology of aberrant mTOR signaling provided us with a
      scientific rationale to target this pathway therapeutically. On this mechanistic
      basis, we treated three consecutive patients with metastatic PEComa with an oral
      mTOR inhibitor, sirolimus. PATIENTS AND METHODS Patients with advanced PEComa
      were treated with sirolimus and consented to retrospective collection of data
      from their medical records and analysis of archival tumor specimens. Tumor
      response was determined by computed tomography scans obtained at the clinical
      discretion of the treating physicians. Tumors were assessed for
      immunohistochemical evidence of mTORC1 activation and genetic evidence of
      alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were
      observed in all patients. PEComas demonstrated loss of TSC2 protein expression
      and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was
      identified in one PEComa. CONCLUSION Inhibition of mTORC1, pathologically
      activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational
      mechanistic target for therapy in PEComas. The clinical activity of sirolimus in
      PEComa additionally strengthens the pathobiologic similarities linking PEComas to
      other neoplasms related to the tuberous sclerosis complex.

PMID- 20048178
TI  - Superior vena cava syndrome: a presentation of anaplastic thyroid carcinoma.

PMID- 20048176
TI  - Circulating serum free light chains as predictive markers of AIDS-related
      lymphoma.
AB  - PURPOSE HIV-infected persons have an elevated risk of developing non-Hodgkin's
      lymphoma (NHL); this risk remains increased in the era of effective HIV therapy.
      We evaluated serum immunoglobulin (Ig) proteins as predictors of NHL risk among
      HIV-infected individuals. PATIENTS AND METHODS By using three cohorts of HIV
      infected persons (from 1982 to 2005), we identified 66 individuals who developed
      NHL and 225 matched (by cohort, sex, ethnicity, age, and CD4 count), HIV
      infected, lymphoma-free controls who had available stored prediagnostic blood
      samples. Serum/plasma samples obtained 0 to 2 years and 2 to 5 years before
      diagnosis/selection were assayed for IgG, IgM, and IgA levels; monoclonal (M)
      Igs; and kappa and lambda free light chain (FLC) levels. Patients and matched
      controls were compared by using conditional logistic regression. Results The
      kappa and lambda FLCs were both significantly higher in patients (eg, in 2- to 5
      year window: median kappa, 4.24 v 3.43 mg/dL; median lambda, 4.04 v 3.09 mg/dL)
      and strongly predicted NHL in a dose-response manner up to 2 to 5 years before
      diagnosis/selection (eg, NHL risk 3.76-fold higher with kappa concentration at
      least 2.00 times the upper limit of normal, and 8.13-fold higher with lambda
      concentration at least 2.00 times the upper limit of normal compared with normal
      levels). In contrast, IgG, IgM, and IgA levels were similar in patients and
      controls. M proteins were detected in only two patients with NHL (3%) and in nine
      controls (4%), and they were not significantly associated with NHL risk.
      CONCLUSION Elevated FLCs may represent sensitive markers of polyclonal B-cell
      activation and dysfunction and could be useful for identifying HIV-infected
      persons at increased NHL risk.

PMID- 20048177
TI  - Transformation to aggressive lymphoma in nodular lymphocyte-predominant Hodgkin's
      lymphoma.
AB  - PURPOSE Prior observations suggest a higher risk of transformation of nodular
      lymphocyte-predominant Hodgkin's lymphoma (NLPHL) to aggressive lymphoma, most
      commonly diffuse large B-cell lymphoma (DLBCL), than in classical Hodgkin's
      lymphoma. We evaluated the frequency of transformation in all patients diagnosed
      with NLPHL at the British Columbia Cancer Agency with long-term follow-up.
      PATIENTS AND METHODS The Lymphoid Cancer Database of the British Columbia Cancer
      Agency was searched to identify all patients diagnosed with NLPHL between 1965
      and 2006. After pathologic review, 95 patients with NLPHL were confirmed. Results
      Patients with NLPHL had the following characteristics at diagnosis: median age of
      37 years, 73% male, and 68% stage I or II disease. With a median follow-up time
      for living patients of 6.5 years (range, 2.5 to 33 years), 13 patients (14%)
      experienced transformation to aggressive lymphoma (median time to transformation,
      8.1 years; range, 0.35 to 20.3 years). The actuarial risk of transformation to
      aggressive lymphoma was 7% and 30% at 10 and 20 years, respectively.
      Transformation was more likely in patients with initial splenic involvement (P =
      .006) at the time of diagnosis of NLPHL. The 10-year progression-free and overall
      survival rates in patients with transformed lymphoma were 52% and 62%,
      respectively. CONCLUSION The risk of transformation in patients with NLPHL to
      DLBCL is substantial and underappreciated. Because transformation can occur years
      after the primary diagnosis of NLPHL, long-term follow-up of these individuals is
      necessary to accurately estimate the risk of development of secondary DLBCL.

PMID- 20048179
TI  - Alternating systemic and hepatic artery infusion therapy for resected liver
      metastases from colorectal cancer: a North Central Cancer Treatment Group
      (NCCTG)/ National Surgical Adjuvant Breast and Bowel Project (NSABP) phase II
      intergroup trial, N9945/CI-66.
AB  - PURPOSE Prior trials have shown that surgery followed by hepatic artery infusion
      (HAI) of floxuridine (FUDR) alternating with systemic fluorouracil improves
      survival rates. Oxaliplatin combined with capecitabine has demonstrated activity
      in advanced colorectal cancer. Based on this observation a trial was conducted to
      assess the potential benefit of systemic oxaliplatin and capecitabine alternating
      with HAI of FUDR. The primary end point was 2-year survival. PATIENTS AND METHODS
      Patients with liver-only metastases from colorectal cancer amenable to resection
      or cryoablation were eligible. HAI and systemic therapy was initiated after
      metastasectomy. Alternating courses of HAI consisted of 0.2 mg/m(2)/d FUDR and
      dexamethasone, day 1 through 14 weeks 1 and 2. Systemic therapy included
      oxaliplatin 130 mg/m(2) day 1 with capecitabine at 1,000 mg/m(2) twice daily,
      days 1 through 14, weeks 4 and 5. Two additional 3-week courses of systemic
      therapy were given. Capecitabine was reduced to 850 mg/m(2) twice daily after
      interim review of toxicity. Results Fifty-five of 76 eligible patients were able
      to initiate protocol-directed therapy and completed median of six cycles (range,
      one to six). Three postoperative or treatment-related deaths were reported.
      Overall, 88% of evaluable patients were alive at 2 years. With a median follow-up
      of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving
      the liver. Median disease-free survival was 32.7 months. CONCLUSION Alternating
      HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end
      point of higher than 85% survival at 2 years and was clinically tolerable.
      However, the merits of this approach need to be established with a phase III
      trial.

PMID- 20048180
TI  - Burkitt's lymphoma in early pregnancy.

PMID- 20048181
TI  - Hypoxia-inducible factor-1 {alpha} expression predicts superior survival in
      patients with diffuse large B-cell lymphoma treated with R-CHOP.
AB  - PURPOSE Hypoxia-inducible factor (HIF) controls the expression of genes in
      response to hypoxia, as well as a wide range of other cellular processes. We
      previously showed constitutive stabilization of HIF-1alpha in the majority of
      patients with diffuse large B-cell lymphoma (DLBCL). To our knowledge, the
      prognostic significance of HIF in lymphoma has never been investigated. PATIENTS
      AND METHODS We studied the immunohistochemical protein expression of HIF-1alpha
      on tissue microarrays from 153 patients with DLBCL treated in sequential cohorts
      with cyclophosphamide, doxorubicin, oncovin, and prednisone (CHOP) or rituximab
      CHOP (R-CHOP) from 1999 to 2002. Results were correlated with patient outcome.
      Results Median follow-up for all patients was 80 months. Among all patients, HIF
      1alpha was expressed in 62% of germinal center and 59% of non-germinal center
      patients. With HIF-1alpha analyzed as a dependent variable, there were no
      survival differences in CHOP-treated patients. In the R-CHOP group, however, HIF
      1alpha protein expression correlated with significantly improved progression-free
      survival (PFS) and overall survival (OS). Five-year PFS for HIF-1alpha-positive
      patients was 71% v 43% for HIF-1alpha-negative patients (P = .0187), whereas 5
      year OS was 75% and 54%, respectively (P = .025). In multivariate analysis with
      International Prognostic Index criteria, HIF-1alpha remained a significant
      predictor for PFS (P = .026) and OS (P = .043). Compared with other biomarkers,
      HIF-1alpha correlated only with BCL6 (P = .004). In terms of gene expression, we
      found several common gene associations of HIF-1alpha and the stromal-1 signature
      with genes predominantly involved in regulation of the extracellular matrix (eg,
      BGN, COL1A2, COL5A1, and PLOD2). CONCLUSION The expression of HIF-1alpha protein
      is an important independent favorable prognostic factor for survival in patients
      with DLBCL treated with R-CHOP.

PMID- 20048183
TI  - Randomized study of intensified anthracycline doses for induction and recombinant
      interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to
      70 years: results of the ALFA-9801 study.
AB  - PURPOSE In patients with acute myeloid leukemia (AML), induction chemotherapy is
      based on standard doses of anthracyclines and cytarabine. High doses of
      cytarabine have been reported as being too toxic for patients older than age 50
      years, but few studies have evaluated intensified doses of anthracyclines.
      PATIENTS AND METHODS In this randomized Acute Leukemia French Association 9801
      (ALFA-9801) study, high doses of daunorubicin (DNR; 80 mg/m(2)/d x 3 days) or
      idarubicin (IDA4; 12 mg/m(2)/d x 4 days) were compared with standard doses of
      idarubicin (IDA3; 12 mg/m(2)/d x 3 days) for remission induction in patients age
      50 to 70 years, with an event-free survival (EFS) end point. After two
      consolidation courses based on intermediate doses of cytarabine, patients in
      continuous remission were randomly assigned to receive or not receive maintenance
      therapy with recombinant interleukin-2 (rIL-2; 5 x 10(6) U/m(2) x 5 days each
      month) for a total duration of 12 months. A total of 468 patients entered the
      study (median age, 60 years). Results Overall complete remission rate was 77%
      with significant differences among the three randomization arms (83%, 78%, and
      70% in the IDA3, IDA4, and DNR arms, respectively; P = .04). However, no
      significant differences were observed in relapse incidence, EFS, or overall
      survival among the three arms. In the 161 patients randomly assigned for
      maintenance therapy, no difference in outcome was observed between the rIL-2 and
      the no further treatment arms. CONCLUSION Neither intensification of
      anthracycline doses nor maintenance with rIL-2 showed a significant impact on AML
      course, at least as scheduled in this trial.

PMID- 20048182
TI  - Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully
      human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial
      growth factor receptor-2.
AB  - PURPOSE To evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics
      (PKs), pharmacodynamics, and preliminary anticancer activity of ramucirumab (IMC
      1121B), a fully human immunoglobulin G(1) monoclonal antibody targeting the
      vascular endothelial growth factor receptor (VEGFR)-2. PATIENTS AND METHODS
      Patients with advanced solid malignancies were treated once weekly with
      escalating doses of ramucirumab. Blood was sampled for PK studies throughout
      treatment. The effects of ramucirumab on circulating vascular endothelial growth
      factor-A (VEGF-A), soluble VEGFR-1 and VEGFR-2, tumor perfusion, and vascularity
      using dynamic contrast-enhanced magnetic resonance imaging were assessed. Results
      Thirty-seven patients were treated with 2 to 16 mg/kg of ramucirumab. After one
      patient each developed dose-limiting hypertension and deep venous thrombosis at
      16 mg/kg, the next lower dose (13 mg/kg) was considered the MTD. Nausea,
      vomiting, headache, fatigue, and proteinuria were also noted. Four (15%) of 27
      patients with measurable disease had a partial response (PR), and 11 (30%) of 37
      patients had either a PR or stable disease lasting at least 6 months. PKs were
      characterized by dose-dependent elimination and nonlinear exposure consistent
      with saturable clearance. Mean trough concentrations exceeded biologically
      relevant target levels throughout treatment at all dose levels. Serum VEGF-A
      increased 1.5 to 3.5 times above pretreatment values and remained in this range
      throughout treatment at all dose levels. Tumor perfusion and vascularity
      decreased in 69% of evaluable patients. CONCLUSION Objective antitumor activity
      and antiangiogenic effects were observed over a wide range of dose levels,
      suggesting that ramucirumab may have a favorable therapeutic index in treating
      malignancies amenable to VEGFR-2 inhibition.

PMID- 20048184
TI  - Efficacy of low-dose interferon {alpha}2a 18 versus 60 months of treatment in
      patients with primary melanoma of >= 1.5 mm tumor thickness: results of a
      randomized phase III DeCOG trial.
AB  - PURPOSE Low-dose (LD) interferon (IFN) alfa (LDI) has demonstrated a consistent
      disease-free survival benefit for patients with clinically lymph node-negative
      melanoma in clinical trials. However, the optimal duration of treatment is still
      under discussion, and no previous trial has evaluated this question specifically.
      A prolongation of LDI from 18 months to 60 months might be of clinical benefit
      for patients with intermediate or high-risk melanoma. PATIENTS AND METHODS Eight
      hundred fifty patients with resected cutaneous melanoma of at least 1.5 mm tumor
      thickness were included in this prospective randomized, multicenter trial in
      Germany and Austria. Patients had to be clinically lymph node-negative, and
      sentinel node biopsy (SLNB) was performed in a majority of cases. They were
      randomly assigned to receive 3 MU IFNalpha2a three times a week subcutaneously
      for either 18 months (arm A) or 60 months (arm B). Results Of 850 randomly
      assigned patients, 840 were eligible for evaluation after a median follow-up of
      4.3 years. Tumor thickness and other relevant prognostic factors were well
      balanced between both groups. SLNB was performed in 635 patients (75.6%), with a
      positivity rate of 18.0% in arm A and 17.5% in arm B. Neither relapse-free
      survival (arm A, 75.6% v arm B, 72.6%; P = .72; hazard ratio, 1.05; 95% CI, 0.80
      to 1.39) nor distant-metastasis-free survival (81.9% v 79.7%; P = .56; HR, 1.10;
      95% CI, 0.80 to 1.52) or overall survival (85.9% v 84.9%; P = .86; HR, 1.03; 95%
      CI, 0.71 to 1.50) showed significant differences. CONCLUSION A prolongation of
      conventional LDI therapy from 18 to 60 months showed no clinical benefit in
      patients with intermediate and high-risk primary melanoma.

PMID- 20048185
TI  - Exercise, tea consumption, and depression among breast cancer survivors.
AB  - PURPOSE To examine the association of lifestyle factors and supplement use with
      depression among breast cancer survivors. PATIENTS AND METHODS In a population
      based cohort study conducted between April 2002 and December 2006 in Shanghai,
      China, a total of 1,399 women who were diagnosed with stage 0 to III breast
      cancer completed 6-month and 18-month postdiagnosis, in-person interviews.
      Information on sociodemographic, clinical, and lifestyle factors were collected
      through the interviews and through review of medical charts at approximately 6
      months postdiagnosis. A metabolic equivalent (MET) score was calculated from
      reported exercise activities. Quality of life (QOL) was evaluated by the Medical
      Outcomes Short Form-36 Health Survey at 6 months postdiagnosis. Depressive
      symptoms were measured by using a 20-item Center for Epidemiological Studies
      Depression Scale at approximately 18 months postdiagnosis. Results Overall, 26%
      of women reported depressive symptoms and 13% met the criteria of clinical
      depression at 18 months postdiagnosis. Women with a higher exercise level (ie,
      >/= 8.3 MET h/wk) were less likely to have depression than nonexercisers; the
      multivariate adjusted odds ratios (ORs) were 0.71 (95% CI, 0.47 to 1.07) for mild
      depression and 0.56 (95% CI, 0.35 to 0.88) for clinical depression in analyses
      controlled for sociodemographic and clinical factors and baseline QOL. Women who
      increased their exercise level had lower risk for depression. Regular tea
      consumption (ie, > 100 g dried tea leaves/mo) was inversely associated with
      overall depression (OR, 0.39; 95% CI, 0.19 to 0.84). No associations were found
      for dietary intake or supplement use with depression. CONCLUSION Regular exercise
      participation and tea consumption may play an important role in the prevention of
      depression among breast cancer survivors.

PMID- 20048186
TI  - Investigational immunotherapeutics for B-cell malignancies.
AB  - The use of rituximab-based chemoimmunotherapy regimens has remarkably improved
      the response rates, long-term outcomes, and quality of life of patients with B
      cell malignancies. However, a substantial number of patients exhibit either
      primary or acquired resistance to rituximab, which suggests that novel
      immunotherapeutics with distinct mechanisms of action are necessary. A series of
      monoclonal antibodies with specificity against different surface antigens
      expressed on malignant B cells (eg, CD22, CD23, CD40, CD70) and novel
      immunotherapeutics (eg, bispecific monoclonal antibodies, small-modular
      immunopharmaceuticals, T-cell engagers) are currently in clinical or final
      preclinical stages of development. Although these agents offer reason for
      optimism, considerable challenges lie ahead in establishing their real clinical
      value, as well as in integrating them into current therapeutic algorithms for
      patients with B-cell malignancies. This review describes some of the most
      promising investigational immunotherapeutics for the treatment of B-cell
      malignancies.

PMID- 20048187
TI  - Bortezomib as induction before autologous transplantation, followed by
      lenalidomide as consolidation-maintenance in untreated multiple myeloma patients.
AB  - PURPOSE To evaluate the effect of bortezomib as induction therapy before
      autologous transplantation, followed by lenalidomide as consolidation-maintenance
      in myeloma patients. PATIENTS AND METHODS Newly diagnosed patients age 65 to 75
      years were eligible. Induction (bortezomib, doxorubicin, and dexamethasone [PAD])
      included four 21-day cycles of bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11),
      pegylated liposomal doxorubicin (30 mg/m(2) on day 4), and dexamethasone (40
      mg/d; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4).
      Autologous transplantation was tandem melphalan 100 mg/m(2) (MEL100) and stem
      cell support. Consolidation included four 28-day cycles of lenalidomide (25 mg/d
      on days 1 to 21 every 28 days) plus prednisone (50 mg every other day), followed
      by maintenance with lenalidomide (LP-L; 10 mg/d on days 1 to 21) until relapse.
      Primary end points were safety (incidence of grade 3 to 4 adverse events [AEs])
      and efficacy (response rate). Results A total of 102 patients were enrolled. In a
      per-protocol analysis, after PAD, 58% of patients had very good partial response
      (VGPR) or better, including 13% with complete response (CR); after MEL100, 82% of
      patients had at least VGPR and 38% had CR; and after LP-L, 86% of patients had at
      least VGPR and 66% had CR. After median follow-up time of 21 months, the 2-year
      progression-free survival rate was 69%, and the 2-year overall survival rate was
      86%. During induction, treatment-related mortality was 3%; grade 3 to 4 AEs
      included thrombocytopenia (17%), neutropenia (10%), peripheral neuropathy (16%),
      and pneumonia (10%). During consolidation-maintenance, grade 3 to 4 AEs were
      neutropenia (16%), thrombocytopenia (6%), pneumonia (5%), and cutaneous rash
      (4%). CONCLUSION Bortezomib as induction before autologous transplantation,
      followed by lenalidomide as consolidation-maintenance, is an effective regimen.

PMID- 20048188
TI  - Validation of a web-based predictive nomogram for ipsilateral breast tumor
      recurrence after breast conserving therapy.
AB  - PURPOSE IBTR! version 1.0 is a web-based tool that uses literature-derived
      relative risk ratios for seven clinicopathologic variables to predict ipsilateral
      breast tumor recurrence (IBTR) after breast-conserving therapy (BCT). Preliminary
      testing demonstrated over-estimation in high-risk subgroups. This study uses two
      independent population-based datasets to create and validate a modified nomogram,
      IBTR! version 2.0. METHODS Cox regression modeling was performed on 7,811
      patients treated with BCT at the British Columbia Cancer Agency (median follow
      up, 9.4 years). Population-based hazard ratios were generated for the seven
      variables in the original nomogram. A modified nomogram was then tested against
      664 patients from Massachusetts General Hospital (median follow-up, 9.3 years).
      The mean predicted and observed 10-year estimates were compared for the entire
      cohort and for four groups predefined by nomogram-predicted risks: group 1: less
      than 3%; group 2: 3% to 5%; group 3: 5% to 10%; and group 4: more than 10%.
      Results IBTR! version 2.0 predicted an overall 10-year IBTR estimate of 4.0% (95%
      CI, 3.8 to 4.2), while the observed estimate was 2.8% (95% CI, 1.6 to 4.7; P =
      .10). The predicted and observed IBTR estimates were: group 1 (n = 283): 2.2%
      versus 1.3%, P = .40; group 2 (n = 237): 3.8% versus 3.5%, P = .80; group 3 (n =
      111): 6.7% versus 3.2%, P = .05; and group 4 (n = 33): 12.5% versus 8.7%, P =
      .50. CONCLUSION IBTR! version 2.0 is accurate in the majority of patients with a
      low to moderate risk of in-breast recurrence. The nomogram still overestimates
      risk in a minority of patients with higher risk features. Validation in a larger
      prospective data set is warranted.

PMID- 20048189
TI  - TP53 mutations and pathologic complete response to neoadjuvant cisplatin and
      fluorouracil chemotherapy in resected oral cavity squamous cell carcinoma.
AB  - PURPOSE To find out if TP53 functional status predicts response to neoadjuvant
      chemotherapy and thus may be helpful during treatment decision making of oral
      cavity squamous cell carcinoma (SCC) patients. PATIENTS AND METHODS We analyzed
      the predictive value of TP53 mutations and their functional status on the basis
      of the transactivation activity of p53 mutant proteins in 53 pretreatment
      biopsies of oral cavity SCC patients receiving primary cisplatin and fluorouracil
      chemotherapy followed by surgery. Results The surgical specimens showed that 15
      patients (28%) achieved a pathologic complete remission (pCR) at both T and N
      sites, and 38 patients had residual tumor cells. Among the 53 pretreatment
      biopsies, 24 (45%) displayed TP53 mutations: 22 single-nucleotide substitutions
      and two deletions. According to functional status that could be determined only
      for the 22 substitutions, 21 mutations were nonfunctional and one was partially
      functional. TP53 mutation was found in four (27%) of 15 patients who achieved a
      pCR and in 20 (53%) of 38 nonresponder patients; the difference was not
      statistically significant (P = .12). In contrast, two (14%) of 14 cases with pCR
      carried a nonfunctional TP53 mutation, a frequency significantly less than that
      found in the nonresponders (19 [51%] of 37; P = .02). TP53 mutation predicted pCR
      in four (17%) of 24 patients and a nonfunctional mutation in only two (9%) of 22
      patients. CONCLUSION The results indicate that the loss of function
      (transactivation activities) of p53 mutant proteins may predict a significant low
      pCR rate and suboptimal response to cisplatin-based neoadjuvant chemotherapy in
      patients with oral cavity SCC.

PMID- 20048190
TI  - Syndecan-1: a critical mediator in cardiac fibrosis.

PMID- 20048191
TI  - Aldosterone, sodium, and hypertension: lessons from torcetrapib?

PMID- 20048193
TI  - Shear stress mediates endothelial adaptations to exercise training in humans.
AB  - Although episodic changes in shear stress have been proposed as the mechanism
      responsible for the effects of exercise training on the vasculature, this
      hypothesis has not been directly addressed in humans. We examined brachial artery
      flow-mediated dilation, an index of NO-mediated endothelial function, in healthy
      men in response to an acute bout of handgrip exercise and across an 8-week period
      of bilateral handgrip training. Shear stress responses were attenuated in one arm
      by cuff inflation to 60 mm Hg. Similar increases were observed in grip strength
      and forearm volume and girth in both limbs. Acute bouts of handgrip exercise
      increased shear rate (P<0.005) and flow-mediated dilation percentage (P<0.05) in
      the uncuffed limb, whereas no changes were evident in the cuffed arm. Handgrip
      training increased flow-mediated dilation percentage in the noncuffed limb at
      weeks 2, 4, and 6 (P<0.001), whereas no changes were observed in the cuffed arm.
      Brachial artery peak reactive hyperemia, an index of resistance artery
      remodeling, progressively increased with training in the noncuffed limb (P<0.001
      and 0.004); no changes were evident in the cuffed arm. Neither acute nor chronic
      shear manipulation during exercise influenced endothelium-independent glyceryl
      trinitrate responses. These results demonstrate that exercise-induced changes in
      shear provide the principal physiological stimulus to adaptation in flow-mediated
      endothelial function and vascular remodeling in response to exercise training in
      healthy humans.

PMID- 20048192
TI  - Plasticity of GABAergic mechanisms within the nucleus of the solitary tract in
      hypertension.

PMID- 20048194
TI  - Vascular endothelial function is related to white blood cell count and
      myeloperoxidase among healthy middle-aged and older adults.
AB  - Endothelium-dependent dilation (EDD) is impaired with aging, but there is
      significant variability among healthy middle-aged and older adults. We tested the
      hypothesis that EDD is related to white blood cell (WBC) count in healthy men and
      women aged 55 to 75 years (n=48) who have a WBC count within the clinically
      normal range. The peak forearm blood flow response to intrabrachial artery
      infusion of acetylcholine was inversely related to WBC count (r=-0.38; P=0.004)
      and was 34% smaller in subjects with higher versus lower WBC count (more versus
      less than the median of 5.0x10(9) cells per liter; P=0.001). Vascular smooth
      muscle responsiveness to NO (peak forearm blood flow response to sodium
      nitroprusside) was inversely related to WBC count (r=-0.30; P=0.02) but did not
      fully explain the associations with EDD. Inhibition of NO with N(G)-monomethyl-L
      arginine reduced EDD in subjects with lower (-56%; P=0.01) but not higher WBC
      count. Tetrahydrobiopterin selectively improved EDD in subjects with higher WBC
      count (+35%; P=0.01) by increasing NO bioavailability. EDD was related (P<0.05)
      to neutrophil, eosinophil, and monocyte but not lymphocyte or basophil counts.
      Myeloperoxidase, which is secreted by neutrophils and monocytes, consumes NO and
      produces molecules that oxidize tetrahydrobiopterin, was inversely related to EDD
      (r=-0.35; P=0.02), and was 42% higher in subjects with a higher WBC count
      (P=0.02). No other factors contributed to the relation between EDD and WBC count.
      Among healthy middle-aged and older adults, impaired EDD is related to higher
      neutrophil, eosinophil, and monocyte-based WBC count mediated by reduced
      responsiveness to NO and increased myeloperoxidase-associated reductions in
      tetrahydrobiopterin and NO bioavailability.

PMID- 20048195
TI  - Intraaortic pulse pressure amplification in subjects at high coronary risk.
AB  - Peripheral (brachial) pulse pressure normally exceeds central (aortic) pulse
      pressure but is a less powerful predictor of cardiovascular risk. The difference
      between the 2 variables, called pulse pressure amplification, has never been
      specifically studied between the proximal and distal aorta in coronary patients.
      Our goal was to determine aortic pulse pressure amplification in subjects at high
      coronary risk, with emphasis on associated renal and inflammatory factors. Blood
      pressure was measured invasively in the ascending aorta, abdominal aorta (at the
      level of kidneys), and iliac artery in 101 subjects (mean age, 63+/-11 years; 61
      men) undergoing coronary angiography. Independently of age, sex, and the presence
      of coronary stenosis, the increase of pulse pressure between the ascending and
      terminal aorta was over 10 mm Hg (P<0.001), whereas mean blood pressure remained
      unchanged. Pulse pressure amplification did not differ significantly between
      patients with and without coronary artery stenosis. Irrespective of confounding
      variables, high pulse pressure measured in the ascending aorta and at the level
      of renal arteries (but not in the iliac artery) was independently related to
      proteinuria. The increase in pulse pressure from the ascending aorta to the renal
      level was negatively associated with leukocyte count, even after multivariate
      adjustment (beta coefficient, -0.19; 95% CI, -0.39 to 0.0; P<0.05). Increased
      plasma creatinine and aortic pulse wave velocity were independently and
      positively correlated (beta coefficient, 0.36; CI, 0.18 to 0.54; P<0.001).
      Independently of coronary atherosclerosis, aortic pulse pressure integrates the
      predictive value of aortic, inflammatory, and renal factors.

PMID- 20048196
TI  - Sympathetic nervous system modulation of inflammation and remodeling in the
      hypertensive heart.
AB  - Chronic activation of the sympathetic nervous system is a key component of
      cardiac hypertrophy and fibrosis. However, previous studies have provided
      evidence that also implicate inflammatory cells, including mast cells (MCs), in
      the development of cardiac fibrosis. The current study investigated the potential
      interaction of cardiac MCs with the sympathetic nervous system. Eight-week-old
      male spontaneously hypertensive rats were sympathectomized to establish the
      effect of the sympathetic nervous system on cardiac MC density, myocardial
      remodeling, and cytokine production in the hypertensive heart. Age-matched Wistar
      Kyoto rats served as controls. Cardiac fibrosis and hypertension were
      significantly attenuated and left ventricular mass normalized, whereas cardiac MC
      density was markedly increased in sympathectomized spontaneously hypertensive
      rats. Sympathectomy normalized myocardial levels of interferon-gamma, interleukin
      6, and interleukin 10, but had no effect on interleukin 4. The effects of
      norepinephrine and substance P on isolated cardiac MC activation were
      investigated as potential mechanisms of interaction between the two. Only
      substance P elicited MC degranulation. Substance P was also shown to induce the
      production of angiotensin II by a mixed population of isolated cardiac
      inflammatory cells, including MCs, lymphocytes, and macrophages. These results
      demonstrate the ability of neuropeptides to regulate inflammatory cell function,
      providing a potential mechanism by which the sympathetic nervous system and
      afferent nerves may interact with inflammatory cells in the hypertensive heart.

PMID- 20048197
TI  - Cyclin-dependent kinase 5 phosphorylates endothelial nitric oxide synthase at
      serine 116.
AB  - Nitric oxide (NO) production in endothelial cells (EC) is regulated by multisite
      phosphorylation of specific serine and threonine residues in endothelial NO
      synthase (eNOS). Among these, eNOS-Ser116 is phosphorylated in the basal state,
      and its phosphorylation contributes to basal NO production. Here, we investigated
      the mechanism by which eNOS-Ser116 is phosphorylated during the basal state using
      bovine aortic EC. Although a previous study suggested that protein kinase C was
      involved in eNOS-Ser116 phosphorylation, overexpression of various protein kinase
      C isoforms did not affect eNOS-Ser116 phosphorylation. An in silico analysis
      using a motif scan revealed that the eNOS-Ser116 residue might be a substrate for
      proline-directed protein kinases. Roscovitine, a specific inhibitor of cyclin
      dependent kinase (CDK), 1, 2, and 5, but not an inhibitor of mitogen-activated
      protein kinase kinase or glycogen synthase kinase 3beta, inhibited eNOS-Ser116
      phosphorylation dose dependently. Furthermore, purified CDK1, 2, or 5 directly
      phosphorylated eNOS-Ser116 in vitro. Ectopic expression of the dominant-negative
      CDK5 but not dominant-negative CDK1 or dominant-negative CDK2 repressed eNOS
      Ser116 phosphorylation and increased NO production. In addition, CDK5 activity
      was detected in bovine aortic EC, and coimmunoprecipitation and confocal
      microscopy studies revealed a colocalization of eNOS and CDK5. Cotransfection of
      CDK5 and p25, the specific CDK5 activator, increased eNOS-Ser116 phosphorylation
      and decreased NO production, but its parent molecule, p35, and p39, another
      activator, were not detected in bovine aortic EC, which suggests the existence of
      a novel CDK5 activator. Overall, this is the first study to find that CDK5 is a
      physiological kinase responsible for eNOS-Ser116 phosphorylation and regulation
      of NO production.

PMID- 20048198
TI  - Syndecan-1 amplifies angiotensin II-induced cardiac fibrosis.
AB  - Syndecan-1 (Synd1) is a transmembrane heparan sulfate proteoglycan that functions
      as a coreceptor for various growth factors and modulates signal transduction. The
      present study investigated whether Synd1, by affecting growth factor signaling,
      may play a role in hypertension-induced cardiac fibrosis and dysfunction.
      Expression of Synd1 was increased significantly in mouse hearts with angiotensin
      II-induced hypertension, which was spatially related to cardiac fibrosis.
      Angiotensin II significantly impaired fractional shortening and induced cardiac
      fibrosis in wild-type mice, whereas these effects were blunted in Synd1-null
      mice. Angiotensin II significantly increased cardiac expression of connective
      tissue growth factor and collagen type I and III in wild-type mice, which was
      blunted in Synd1-null mice. These findings were confirmed in vitro, where
      angiotensin II induced the expression of both connective tissue growth factor and
      collagen I in fibroblasts. The absence of Synd1 in either Synd1-null fibroblasts,
      after knockdown of Synd1 by short hairpin RNA, or after inhibition of heparan
      sulfates by protamine attenuated this increase, which was associated with reduced
      phosphorylation of Smad2. In conclusion, loss of Synd1 reduces cardiac fibrosis
      and dysfunction during angiotensin II-induced hypertension.

PMID- 20048199
TI  - Blood pressure, blood flow, and oxygenation in the clipped kidney of chronic 2
      kidney, 1-clip rats: effects of tempol and Angiotensin blockade.
AB  - Angiotensin II maintains renal cortical blood flow and renal oxygenation in the
      clipped kidney of early 2-kidney, 1-clip Goldblatt hypertensive (2K,1C) rats. The
      involvement of Ang II is believed to decline, whereas oxidative stress increases
      during the progression of 2K,1C hypertension. We investigated the hypothesis that
      the acute administration of drugs to inhibit reactive oxygen species (Tempol),
      angiotensin II type 1 receptors (candesartan), or angiotensin-converting enzyme
      (enalaprilat) lowers mean arterial pressure and increases kidney blood flow and
      oxygenation in the clipped kidney of chronic 2K,1C rats in contrast to sham
      controls. Twelve months after left renal artery clipping or sham, mean arterial
      pressure, renal cortical blood flow, and renal cortical and medullary oxygen
      tension were measured after acute administration of Tempol followed by
      enalaprilat or candesartan followed by enalaprilat. The mean arterial pressure of
      the 2K,1C rat was reduced by candesartan (-9%) and, more effectively, by Tempol (
      35%). All of the applied treatments had similar blood pressure-lowering effects
      in sham rats (average: -21%). Only Tempol increased cortical blood flow (+35%)
      and cortical and medullary oxygen tensions (+17% and +94%, respectively) in
      clipped kidneys of 2K,1C rats. Administration of enalaprilat had no additional
      effect, except for a modest reduction in cortical blood flow in the clipped
      kidney of 2K,1C rats when coadministered with candesartan (-10%). In conclusion,
      acute administration of Tempol is more effective than candesartan in reducing the
      mean arterial blood pressure and improving renal blood perfusion and oxygenation
      in the clipped kidney of chronic 2K,1C rats.

PMID- 20048200
TI  - Varenicline for smoking cessation in patients with coronary heart disease.

PMID- 20048201
TI  - Too much, too little, or just right?: untangling endogenous erythropoietin in
      heart failure.

PMID- 20048202
TI  - Get with the guidelines: a new chapter?

PMID- 20048203
TI  - Feeling the elephant of cardiovascular cell therapy.

PMID- 20048204
TI  - Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis:
      results of the aortic stenosis progression observation: measuring effects of
      rosuvastatin (ASTRONOMER) trial.
AB  - BACKGROUND: Aortic stenosis (AS) is an active process with similarities to
      atherosclerosis. The objective of this study was to assess the effect of
      cholesterol lowering with rosuvastatin on the progression of AS. METHODS AND
      RESULTS: This was a randomized, double-blind, placebo-controlled trial in
      asymptomatic patients with mild to moderate AS and no clinical indications for
      cholesterol lowering. The patients were randomized to receive either placebo or
      rosuvastatin 40 mg daily. A total of 269 patients were randomized: 134 patients
      to rosuvastatin 40 mg daily and 135 patients to placebo. Annual echocardiograms
      were performed to assess AS progression, which was the primary outcome; the
      median follow-up was 3.5 years. The peak AS gradient increased in patients
      receiving rosuvastatin from a baseline of 40.8+/-11.1 to 57.8+/-22.7 mm Hg at the
      end of follow-up and in patients with placebo from 41.6+/-10.9 mm Hg at baseline
      to 54.8+/-19.8 mm Hg at the end of follow-up. The annualized increase in the peak
      AS gradient was 6.3+/-6.9 mm Hg in the rosuvastatin group and 6.1+/-8.2 mm Hg in
      the placebo group (P=0.83). Treatment with rosuvastatin was not associated with a
      reduction in AS progression in any of the predefined subgroups. CONCLUSIONS:
      Cholesterol lowering with rosuvastatin 40 mg did not reduce the progression of AS
      in patients with mild to moderate AS; thus, statins should not be used for the
      sole purpose of reducing the progression of AS. Clinical Trial Registration
      Information- URL: http://www.controlled-trials.com/. CLINICAL TRIAL REGISTRATION
      NUMBER: ISRCTN 32424163.

PMID- 20048205
TI  - Joint effects of physical activity, body mass index, waist circumference, and
      waist-to-hip ratio on the risk of heart failure.
AB  - BACKGROUND: Obesity increases heart failure (HF) risk; however, the independent
      effect of physical activity and the joint effect of physical activity and
      adiposity on HF risk are not established. We evaluated the single and joint
      associations of physical activity and different indicators of adiposity (body
      mass index, waist circumference, and waist-to-hip ratio) with HF risk. METHODS
      AND RESULTS: Study cohorts included 59 178 Finnish participants who were 25 to 74
      years of age and free of HF at baseline. During a mean follow-up of 18.4 years,
      1921 men and 1693 women developed HF. The multivariable-adjusted hazard ratios of
      HF associated with low, moderate, and high physical activity were 1.00, 0.79, and
      0.69 (P(trend)<0.001) for men and 1.00, 0.86, and 0.68 (P(trend)<0.001) for
      women, respectively. The multivariable-adjusted hazard ratios of HF at different
      levels of body mass index (<25, 25 to 29.9, and >or=30 kg/m(2)) were 1.00, 1.25,
      and 1.99 (P(trend)<0.001) for men and 1.00, 1.33, and 2.06 (P(trend)<0.001) for
      women, respectively. Abdominal adiposity, measured by waist circumference or
      waist-to-hip ratio, was associated with a greater risk of HF among both men and
      women (all P(trend)<0.01). In joint analyses, the protective effect of physical
      activity was consistent in subjects at all levels of body mass index.
      CONCLUSIONS: General overweight and general and abdominal obesity are
      independently associated with an increased risk of HF, whereas moderate or high
      levels of physical activity are associated with a reduced risk of HF. The
      protective effect of physical activity on HF risk is observed at all levels of
      body mass index.

PMID- 20048206
TI  - Effects of right ventricular ejection fraction on outcomes in chronic systolic
      heart failure.
AB  - BACKGROUND: Studies of the effect of right ventricular ejection fraction (RVEF)
      on outcomes in heart failure (HF) are limited by small sample size and short
      follow-up. METHODS AND RESULTS: We examined the effect of baseline RVEF on
      outcomes in 2008 Beta-Blocker Evaluation of Survival Trial (BEST) participants
      with HF and left ventricular ejection fraction <or=35% during 24 months of mean
      follow-up. RVEF, estimated by gated-equilibrium radionuclide ventriculography,
      was used to categorize patients into 4 RVEF groups: >or=40% (n=733), 30% to 39%
      (n=531), 20% to 29% (n=473), and <20% (n=271). Unadjusted rates for all-cause
      mortality in patients with RVEF >or=40%, 30% to 39%, 20% to 29%, and <20% were
      27%, 32%, 35%, and 47%, respectively. When compared with patients with RVEF
      >or=40%, unadjusted hazard ratios and 95% confidence intervals for all-cause
      mortality for those with RVEF 30% to 39%, 20% to 29%, and <20% were 1.19 (0.97 to
      1.46; P=0.087), 1.45 (1.17 to 1.78; P=0.001), and 1.98 (1.59 to 2.47; P<0.0001),
      respectively. Respective multivariable-adjusted hazard ratios (95% confidence
      intervals) for all-cause mortality associated with RVEF 30% to 39%, 20% to 29%,
      and <20% were 1.07 (0.87 to 1.32; P=0.518), 1.12 (0.89 to 1.40; P=0.328), and
      1.32 (1.02 to 1.71; P=0.034), respectively. Adjusted hazard ratios (95%
      confidence intervals) for other outcomes associated with RVEF <20% (compared with
      >or=40%) were as follows: cardiovascular mortality, 1.33 (1.01 to 1.76; P=0.041);
      HF mortality, 1.61 (1.03 to 2.52; P=0.037); sudden cardiac death, 1.29 (0.87 to
      1.91; P=0.212); all-cause hospitalization, 1.21 (1.00 to 1.47; P=0.056); and HF
      hospitalization, 1.39 (1.10 to 1.77; P=0.007). CONCLUSIONS: Baseline RVEF <20% is
      a significant independent predictor of mortality and HF hospitalization in
      systolic HF.

PMID- 20048207
TI  - Adherence of catheterization laboratory cardiologists to American College of
      Cardiology/American Heart Association guidelines for percutaneous coronary
      interventions and coronary artery bypass graft surgery: what happens in actual
      practice?
AB  - BACKGROUND: The American College of Cardiology and the American Heart Association
      have issued guidelines for the use of coronary artery bypass graft surgery (CABG)
      and percutaneous coronary interventions (PCI) for many years, but little is known
      about the impact of these evidence-based guidelines on referral decisions.
      METHODS AND RESULTS: A cardiac catheterization laboratory database used by 19
      hospitals in New York State was used to identify treatment (CABG surgery, PCI,
      medical treatment, or nothing) recommended by the catheterization laboratory
      cardiologist for patients undergoing catheterization with asymptomatic/mild
      angina, stable angina, and unstable angina/non-ST-elevation myocardial infarction
      between January 1, 2005, and August 31, 2007. The recommended treatment was
      compared with indications for these patients based on American College of
      Cardiology/American Heart Association guidelines. Of the 16 142 patients
      undergoing catheterization who were found to have coronary artery disease, the
      catheterization laboratory cardiologist was the final source of recommendation
      for 10 333 patients (64%). Of these 10 333 patients, 13% had indications for CABG
      surgery, 59% for PCI, and 17% for both CABG surgery and PCI. Of the patients who
      had indications for CABG surgery, 53% were recommended for CABG and 34% for PCI.
      Of the patients with indications for PCI, 94% were recommended for PCI. For the
      patients who had indications for both CABG surgery and PCI, 93% were recommended
      for PCI and 5% for CABG surgery. Catheterization laboratory cardiologists in
      hospitals with PCI capability were more likely to recommend patients for PCI than
      hospitals in which only catheterization was performed. CONCLUSIONS: Patients with
      coronary artery disease receive more recommendations for PCI and fewer
      recommendations for CABG surgery than indicated in the American College of
      Cardiology/American Heart Association guidelines.

PMID- 20048208
TI  - Relations of biomarkers of distinct pathophysiological pathways and atrial
      fibrillation incidence in the community.
AB  - BACKGROUND: Biomarkers of multiple pathophysiological pathways have been related
      to incident atrial fibrillation (AF), but their predictive ability remains
      controversial. METHODS AND RESULTS: In 3120 Framingham cohort participants (mean
      age 58.4+/-9.7 years, 54% women), we related 10 biomarkers that represented
      inflammation (C-reactive protein and fibrinogen), neurohormonal activation (B
      type natriuretic peptide [BNP] and N-terminal proatrial natriuretic peptide),
      oxidative stress (homocysteine), the renin-angiotensin-aldosterone system (renin
      and aldosterone), thrombosis and endothelial function (D-dimer and plasminogen
      activator inhibitor type 1), and microvascular damage (urinary albumin excretion;
      n=2673) to incident AF (n=209, 40% women) over a median follow-up of 9.7 years
      (range 0.05 to 12.8 years). In multivariable-adjusted analyses, the biomarker
      panel was associated with incident AF (P<0.0001). In stepwise-selection models
      (P<0.01 for entry and retention), log-transformed BNP (hazard ratio per SD 1.62,
      95% confidence interval 1.41 to 1.85, P<0.0001) and C-reactive protein (hazard
      ratio 1.25, 95% confidence interval 1.07 to 1.45, P=0.004) were chosen. The
      addition of BNP to variables recently combined in a risk score for AF increased
      the C-statistic from 0.78 (95% confidence interval 0.75 to 0.81) to 0.80 (95%
      confidence interval 0.78 to 0.83) and showed an integrated discrimination
      improvement of 0.03 (95% confidence interval 0.02 to 0.04, P<0.0001), with 34.9%
      relative improvement in reclassification analysis. The combined analysis of BNP
      and C-reactive protein did not appreciably improve risk prediction over the model
      that incorporated BNP in addition to the risk factors. CONCLUSIONS: BNP is a
      predictor of incident AF and improves risk stratification based on well
      established clinical risk factors. Whether knowledge of BNP concentrations may be
      used to target individuals at risk of AF for more intensive monitoring or primary
      prevention requires further investigation.

PMID- 20048209
TI  - Intracoronary administration of cardiac progenitor cells alleviates left
      ventricular dysfunction in rats with a 30-day-old infarction.
AB  - BACKGROUND: Administration of cardiac progenitor cells (CPCs) 4 hours after
      reperfusion ameliorates left ventricular function in rats with acute myocardial
      infarction (MI). Clinically, however, this approach is not feasible, because
      expansion of autologous CPCs after acute MI requires several weeks. Therefore, we
      sought to determine whether CPCs are beneficial in the more clinically relevant
      setting of an old MI (scar). METHODS AND RESULTS: One month after coronary
      occlusion/reperfusion, rats received an intracoronary infusion of vehicle or
      enhanced green fluorescent protein-labeled CPCs. Thirty-five days later, CPC
      treated rats exhibited more viable myocardium in the risk region, less fibrosis
      in the noninfarcted region, and improved left ventricular function. Cells that
      stained positive for enhanced green fluorescent protein that expressed
      cardiomyocyte, endothelial, and vascular smooth muscle cell markers were observed
      only in 7 of 17 treated rats and occupied only 2.6% and 1.1% of the risk and
      noninfarcted regions, respectively. Transplantation of CPCs was associated with
      increased proliferation and expression of cardiac proteins by endogenous CPCs.
      CONCLUSIONS: Intracoronary administration of CPCs in the setting of an old MI
      produces beneficial structural and functional effects. Although exogenous CPCs
      can differentiate into new cardiac cells, this mechanism is not sufficient to
      explain the benefits, which suggests paracrine effects; among these, the present
      data identify activation of endogenous CPCs. This is the first report that CPCs
      are beneficial in the setting of an old MI when given by intracoronary infusion,
      the most widely applicable therapeutic approach in patients. Furthermore, this is
      the first evidence that exogenous CPC administration activates endogenous CPCs.
      These results open the door to new therapeutic applications for the use of
      autologous CPCs in patients with old MI and chronic ischemic cardiomyopathy.

PMID- 20048210
TI  - Efficacy and safety of varenicline for smoking cessation in patients with
      cardiovascular disease: a randomized trial.
AB  - BACKGROUND: Smoking cessation is a key component of secondary cardiovascular
      disease prevention. Varenicline, a partial alpha4beta2 nicotinic acetylcholine
      receptor agonist, is effective for smoking cessation in healthy smokers, but its
      efficacy and safety in smokers with cardiovascular disease are unknown. METHODS
      AND RESULTS: A multicenter, randomized, double-blind, placebo-controlled trial
      compared the efficacy and safety of varenicline with placebo for smoking
      cessation in 714 smokers with stable cardiovascular disease. Participants
      received varenicline (1 mg twice daily) or placebo, along with smoking-cessation
      counseling, for 12 weeks. Follow-up lasted 52 weeks. The primary end point was
      carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 (last
      4 weeks of treatment). The continuous abstinence rate was higher for varenicline
      than placebo during weeks 9 through 12 (47.0% versus 13.9%; odds ratio, 6.11; 95%
      confidence interval [CI], 4.18 to 8.93) and weeks 9 through 52 (19.2% versus
      7.2%; odds ratio, 3.14; 95% CI, 1.93 to 5.11). The varenicline and placebo groups
      did not differ significantly in cardiovascular mortality (0.3% versus 0.6%;
      difference, -0.3%; 95% CI, -1.3 to 0.7), all-cause mortality (0.6% versus 1.4%;
      difference, -0.8%; 95% CI, -2.3 to 0.6), cardiovascular events (7.1% versus 5.7%;
      difference, 1.4%; 95% CI, -2.3 to 5.0), or serious adverse events (6.5% and 6.0%;
      difference, 0.5%; 95% CI, -3.1 to 4.1). As a result of adverse events, 9.6% of
      varenicline and 4.3% of placebo participants discontinued study drug.
      CONCLUSIONS: Varenicline is effective for smoking cessation in smokers with
      cardiovascular disease. It was well tolerated and did not increase cardiovascular
      events or mortality; however, trial size and duration limit definitive
      conclusions about safety. Clinical Trial Registration Information- URL:
      http://www.clinicaltrials.gov/ct2/show/NCT00282984. Unique identifier:
      NCT00282984.

PMID- 20048211
TI  - Soluble CD40 ligand impairs the function of peripheral blood angiogenic outgrowth
      cells and increases neointimal formation after arterial injury.
AB  - BACKGROUND: Recent work has revealed an essential involvement of soluble CD40
      ligand (sCD40L) in inflammation and atherosclerosis. We investigated whether
      sCD40L functionally affects peripheral blood-derived angiogenic early outgrowth
      cells (EOCs) and neointimal remodeling after arterial injury. METHODS AND
      RESULTS: Besides myeloid and endothelial markers, cultured human EOCs strongly
      expressed CD40 mRNA and protein. EOC adhesion to fibronectin, fibrinogen,
      intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 under
      flow conditions, as well as their transmigration toward stromal cell-derived
      factor-1alpha, was dose-dependently reduced after preincubation with recombinant
      human sCD40L for 24 hours. Integrin expression was unaffected by sCD40L, implying
      that integrin adhesiveness was attenuated. Surface-immobilized CD40L supported
      much lower adhesion of EOCs than fibronectin. Treatment of EOCs with sCD40L
      increased superoxide anion production and decreased viability and proliferation.
      Notably, CD40(-/-) mice displayed reduced neointima and improved re
      endothelialization after carotid wire injury compared with wild-type mice, and
      therapeutic infusion of control EOCs but not EOCs pretreated with sCD40L
      attenuated neointimal growth after wire injury in nude mice. Furthermore,
      neointimal growth was more markedly diminished by infusion of spleen-derived
      CD40(-/-) mouse EOCs than by that of wild-type EOCs. Preincubation of wild-type
      EOCs but not CD40(-/-) EOCs with sCD40L before their infusion markedly aggravated
      neointimal formation. Treatment with sCD40L attenuated luminal incorporation of
      EOCs and accelerated neointimal progression. CONCLUSIONS: Endothelial dysfunction
      due to persistently elevated plasma levels of sCD40L may be attributable to an
      impairment of EOC function. Hence, in the context of arterial injury, therapeutic
      blockade of sCD40L may provide a novel strategy for accelerating endothelial
      regeneration and attenuating neointimal remodeling.

PMID- 20048212
TI  - Update on cardiovascular implantable electronic device infections and their
      management: a scientific statement from the American Heart Association.
AB  - Despite improvements in cardiovascular implantable electronic device (CIED)
      design, application of timely infection control practices, and administration of
      antibiotic prophylaxis at the time of device placement, CIED infections continue
      to occur and can be life-threatening. This has prompted the study of all aspects
      of CIED infections. Recognizing the recent advances in our understanding of the
      epidemiology, risk factors, microbiology, management, and prevention of CIED
      infections, the American Heart Association commissioned this scientific statement
      to educate clinicians about CIED infections, provide explicit recommendations for
      the care of patients with suspected or established CIED infections, and highlight
      areas of needed research.

PMID- 20048213
TI  - Endogenous erythropoietin and outcome in heart failure.
AB  - BACKGROUND: Endogenous erythropoietin is increased in patients with heart failure
      (HF). Previous small-scale data suggest that these erythropoietin levels are
      related to prognosis. This study aims to analyze the clinical and prognostic
      value of erythropoietin levels in relation to hemoglobin in a large cohort of HF
      patients. METHODS AND RESULTS: In patients hospitalized for HF, endogenous
      erythropoietin levels were measured at discharge and after 6 months. In anemic
      patients, the relation between erythropoietin and hemoglobin levels was
      determined by calculating the observed/predicted ratio of erythropoietin levels.
      We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were
      male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median
      erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher
      erythropoietin levels at baseline were independently related to an increased
      mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to
      3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher
      than median at baseline and at 6 months) were related to an increased mortality
      risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The
      observed/predicted ratio was determined in a subset of anemic patients, 79% of
      whom had erythropoietin levels lower than expected and 9% had levels higher than
      expected on the basis of their hemoglobin. Multivariate Cox regression analysis
      revealed that a higher observed/predicted ratio was related to an increased
      mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12;
      P=0.003). CONCLUSIONS: Erythropoietin levels predict mortality in HF patients,
      and persistently elevated levels have an independent prognostic value. In anemic
      HF patients, the majority had a low observed/predicted ratio. However, a higher
      observed/predicted ratio may be related to an independent increased mortality
      risk.

PMID- 20048214
TI  - Ventricular geometry, strain, and rotational mechanics in pulmonary hypertension.
AB  - BACKGROUND: We tested the hypothesis that right ventricular (RV) pressure
      overload affects RV function and further influences left ventricular (LV)
      geometry, which adversely affects LV twist mechanics and segmental function.
      METHODS AND RESULTS: Echocardiographic images were prospectively acquired in 44
      patients (age, 46+/-12 years; 82% women) with evidence of pulmonary hypertension
      (estimated pulmonary artery systolic pressure, 71+/-23 mm Hg) and in 44 age- and
      gender-matched healthy subjects. Patients with intrinsic LV diseases were
      excluded. RV lateral wall longitudinal strain (LS) and interventricular septal
      (IVS) LS were reduced in the pulmonary hypertension group compared with control
      subjects (-15.9+/-7.6% versus -25.5+/-6.1%, P<0.001; and -17.3+/-4.4% versus 
      20.2+/-3.9%, P=0.002, respectively), whereas LV lateral wall LS was preserved. RV
      lateral wall LS and IVS LS, but not LV lateral wall LS, correlated with pulmonary
      artery systolic pressure (r=0.56, P<0.01; r=0.32, P<0.01) and LV eccentricity
      index (r=0.57, P<0.01; r=0.57, P<0.01). IVS and LV lateral wall circumferential
      strain (CS) were both reduced in the pulmonary hypertension group. Although IVS
      CS and LV lateral wall CS correlated with pulmonary artery systolic pressure and
      LV eccentricity index, after adjustment of CS for LV eccentricity index,
      differences between groups persisted for IVS CS (P<0.01) but not LV lateral wall
      CS (P=0.09). LV torsion was decreased in patients with pulmonary hypertension
      compared with control subjects (9.6+/-4.9 degrees versus 14.7+/-4.9 degrees ,
      P<0.001). LV torsion inversely correlated with pulmonary artery systolic pressure
      (r=-0.39, P<0.01) and LV eccentricity index (r=-0.3, P<0.01). LV untwisting rates
      were similar in both groups (P=0.7). CONCLUSIONS: Chronic RV pressure overload
      directly affects RV longitudinal systolic deformation. RV pressure overload
      further influences IVS and LV geometry, which impairs LV torsion and segmental LS
      and CS, more for the IVS than for the free wall of the LV.

PMID- 20048215
TI  - Model for end-stage liver disease score predicts left ventricular assist device
      operative transfusion requirements, morbidity, and mortality.
AB  - BACKGROUND: The Model for End-Stage Liver Disease (MELD) predicts events in
      cirrhotic subjects undergoing major surgery and may offer similar prognostication
      in left ventricular assist device candidates with comparable degrees of
      multisystem dysfunction. METHODS AND RESULTS: Preoperative MELD scores were
      calculated for subjects enrolled in the University of Michigan Health System
      (UMHS) mechanical circulatory support database. Univariate and multiple
      regression analyses were performed to investigate the ability of patient
      characteristics, laboratory data (including MELD scores), and hemodynamic
      measurements to predict total perioperative blood product exposure and operative
      mortality. The ability of preoperative MELD scores to predict operative mortality
      was evaluated in subjects enrolled in the Interagency Registry of Mechanically
      Assisted Circulatory Support (INTERMACS), and results were compared with those
      from the UMHS cohort. The mean+/-SD MELD scores for the UMHS (n=211) and
      INTERMACS (n=324) cohorts were 13.7+/-6.1 and 15.2+/-5.8, respectively, with 29
      (14%) and 19 (6%) perioperative deaths. In the UMHS cohort, median total
      perioperative blood product exposure was 74 units (25th and 75th percentiles, 44
      and 120 units). Each 5-unit MELD score increase was associated with 15.1+/-3.8
      units (beta+/-SE) of total perioperative blood product exposure. Each 10-unit
      increase in total perioperative blood product exposure increased the odds of
      operative death (odds ratio, 1.05; 95% confidence interval, 1.01 to 1.10). Odds
      ratios, measuring the ability of MELD scores to predict perioperative mortality,
      were 1.5 (95% confidence interval, 1.1 to 2.0) and 1.5 (95% confidence interval,
      1.1 to 2.1) per 5 MELD units for the UMHS and INTERMACS cohorts, respectively.
      When MELD scores were dichotomized as >or=17 and <17, risk-adjusted Cox
      proportional-hazard ratios for 6-month mortality were 2.5 (95% confidence
      interval, 1.2 to 5.3) and 2.5 (95% confidence interval, 1.1 to 5.4) for the UMHS
      and INTERMACS cohorts, respectively. CONCLUSIONS: The MELD score identified left
      ventricular assist device candidates at high risk for perioperative bleeding and
      mortality.

PMID- 20048216
TI  - Operative and middle-term results of cardiac surgery in nonagenarians: a bridge
      toward routine practice.
AB  - BACKGROUND: Age >90 years represents in many centers an absolute contraindication
      to cardiac surgery. Nonagenarians are a rapidly growing subset of the population
      posing an expanding clinical problem. To provide helpful information in regard to
      this complex decision, we analyzed the operative and 5-year results of coronary
      and valvular surgical procedures in these patients. METHODS AND RESULTS: We
      retrospectively reviewed 127 patients aged >or=90 years who underwent cardiac
      surgery within our hospital group in the period 1998 to 2008. Kaplan-Meier and
      multiple logistic regression analyses were performed. A longer follow-up than
      most published studies and the largest series published thus far are presented.
      Mean age was 92 years (range, 90 to 103 years). Mean logistic EuroSCORE was
      21.3+/-6.1. Sixty patients had valvular surgery (including 11 valve repairs), 49
      patients had coronary artery bypass grafting, and 18 had valvular plus coronary
      artery bypass grafting surgery (55 left mammary artery grafts implanted). Forty
      five patients (35.4%) were operated on nonelectively. Operative mortality was
      13.4% (17 cases). Fifty-four patients (42.5%) had a complicated postoperative
      course. There were no statistically significant differences in the rate and type
      of complications between patient strata on the basis of type of surgery
      performed. Nonelective priority predicted a complicated postoperative course.
      Predictors of operative mortality were nonelective priority and previous
      myocardial infarction. Kaplan-Meier survival estimates at 5 years were comparable
      between patient groups on the basis of procedure performed. CONCLUSIONS: Although
      the rate of postoperative complications remains high, cardiac surgery in
      nonagenarians can achieve functional improvement at the price of considerable
      operative and follow-up mortality rates. Cardiac operations in these very elderly
      subjects are supported if appropriate selection is made and if the operation is
      performed earlier and electively. Our results should contribute to the
      development of guidelines for cardiac operations in nonagenarians.

PMID- 20048217
TI  - Miranda--the Tempest.

PMID- 20048218
TI  - Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients
      with first-episode schizophrenia.
AB  - CONTEXT: Postmortem investigations and the receptor affinity profile of atypical
      antipsychotics have implicated the participation of serotonin(2A) receptors in
      the pathophysiology of schizophrenia. Most postmortem studies point toward lower
      cortical serotonin(2A) binding in schizophrenic patients. However, in vivo
      studies of serotonin(2A) binding report conflicting results, presumably because
      sample sizes have been small or because schizophrenic patients who were not
      antipsychotic-naive were included. Furthermore, the relationships between
      serotonin(2A) binding, psychopathology, and central neurocognitive deficits in
      schizophrenia are unclear. OBJECTIVES: To assess in vivo brain serotonin(2A)
      binding potentials in a large sample of antipsychotic-naive schizophrenic
      patients and matched healthy controls, and to examine possible associations with
      psychopathology, memory, attention, and executive functions. DESIGN: Case-control
      study. SETTING: University hospital, Denmark. PARTICIPANTS: A sample of 30 first
      episode, antipsychotic-naive schizophrenic patients, 23 males and 7 females, and
      30 matched healthy control subjects. INTERVENTIONS: Positron emission tomography
      with the serotonin(2A)-specific radioligand fluorine 18-labeled altanserin and
      administration of a neuropsychological test battery. MAIN OUTCOME MEASURES:
      Binding potential of specific tracer binding, scores on the Positive and Negative
      Syndrome Scale, and results of neuropsychological testing. RESULTS: Schizophrenic
      patients had significantly lower serotonin(2A) binding in the frontal cortex than
      did control subjects. A significant negative correlation was observed between
      frontal cortical serotonin(2A) binding and positive psychotic symptoms in the
      male patients. No correlations were found between cognitive functions and
      serotonin(2A) binding. CONCLUSION: The results suggest that frontal cortical
      serotonin(2A) receptors are involved in the pathophysiology of schizophrenia.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00207064.

PMID- 20048219
TI  - Metabolic testing rates in 3 state Medicaid programs after FDA warnings and
      ADA/APA recommendations for second-generation antipsychotic drugs.
AB  - CONTEXT: In 2003, the Food and Drug Administration (FDA) required a warning on
      diabetes risk for second-generation antipsychotic (SGA) drugs. The American
      Diabetes Association (ADA) and American Psychiatric Association (APA) recommended
      glucose and lipid testing for all patients starting to receive SGA drugs.
      OBJECTIVE: To characterize associations between the combined warnings and
      recommendations and baseline metabolic testing and SGA drug selection. DESIGN:
      Interrupted time-series analysis. SETTING: California, Missouri, and Oregon.
      Patients A total of 109 451 individuals receiving Medicaid who began taking SGA
      medication and a control cohort of 203 527 patients who began taking albuterol
      but did not receive antipsychotic medication. INTERVENTIONS: Prewarning and
      postwarning trends in metabolic testing were compared using laboratory claims for
      the cohort collected January 1, 2002, through December 31, 2005. Changes in SGA
      prescribing practices were similarly evaluated. MAIN OUTCOME MEASURES: Monthly
      rates of baseline serum glucose and lipid testing for SGA-treated and propensity
      matched albuterol-treated patients and monthly share of new prescriptions for
      each SGA drug. RESULTS: Initial testing rates for SGA-treated patients were low
      (glucose, 27%; lipids, 10%). The warning was not associated with an increase in
      glucose testing among SGA-treated patients and was associated with only a
      marginal increase in lipid testing rates (1.7%; P = .02). Testing rates and
      trends in SGA-treated patients were not different from background rates observed
      in the albuterol control group. New prescriptions of olanzapine (higher metabolic
      risk) declined during the warning period (annual share decline, 19.9%; P < .001).
      New prescriptions of aripiprazole (lower metabolic risk) increased during the
      warning period (share increase, 12.1%; P < .001) but may be attributable to the
      elimination of prior authorization in California during the same time frame.
      Quetiapine, risperidone, and ziprasidone use were not associated with the
      warning. CONCLUSIONS: In a Medicaid-receiving population, baseline glucose and
      lipid testing for SGA-treated patients was infrequent and showed little change
      following the diabetes warning and monitoring recommendations. A change in SGA
      drug selection consistent with intentions to reduce metabolic risk was observed.

PMID- 20048220
TI  - National trends in psychotropic medication polypharmacy in office-based
      psychiatry.
AB  - CONTEXT: Psychotropic medication polypharmacy is common in psychiatric outpatient
      settings and, in some patient groups, may have increased in recent years.
      OBJECTIVE: To examine patterns and recent trends in psychotropic polypharmacy
      among visits to office-based psychiatrists. DESIGN: Annual data from the 1996
      2006 cross-sectional National Ambulatory Medical Care Surveys were analyzed to
      examine patterns and trends in psychotropic polypharmacy within nationally
      representative samples of 13 079 visits to office-based psychiatrists. SETTING:
      Office-based psychiatry practices in the United States. PARTICIPANTS: Outpatients
      with mental disorder diagnoses visiting office-based psychiatrists. MAIN OUTCOME
      MEASURE: Number of medications prescribed in each visit and specific medication
      combinations. RESULTS: There was an increase in the number of psychotropic
      medications prescribed across years; visits with 2 or more medications increased
      from 42.6% in 1996-1997 to 59.8% in 2005-2006; visits with 3 or more medications
      increased from 16.9% to 33.2% (both P < .001). The median number of medications
      prescribed in each visit increased from 1 in 1996-1997 to 2 in 2005-2006 (mean
      increase: 40.1%). The increasing trend of psychotropic polypharmacy was mostly
      similar across visits by different patient groups and persisted after controlling
      for background characteristics. Prescription for 2 or more antidepressants,
      antipsychotics, sedative-hypnotics, and antidepressant-antipsychotic
      combinations, but not other combinations, significantly increased across survey
      years. There was no increase in prescription of mood stabilizer combinations. In
      multivariate analyses, the odds of receiving 2 or more antidepressants were
      significantly associated with a diagnosis of major depression (odds ratio [OR],
      3.44; 99% confidence interval [CI], 2.58-4.58); 2 or more antipsychotics, with
      schizophrenia (OR, 6.75; 99% CI, 3.52-12.92); 2 or more mood stabilizers, with
      bipolar disorder (OR, 15.46; 99% CI, 6.77-35.31); and 2 or more sedative
      hypnotics, with anxiety disorders (OR, 2.13; 99% CI, 1.41-3.22). CONCLUSIONS:
      There has been a recent significant increase in polypharmacy involving
      antidepressant and antipsychotic medications. While some of these combinations
      are supported by clinical trials, many are of unproven efficacy. These trends put
      patients at increased risk of drug-drug interactions with uncertain gains for
      quality of care and clinical outcomes.

PMID- 20048221
TI  - Depression care in the United States: too little for too few.
AB  - OBJECTIVE: To determine the prevalence and adequacy of depression care among
      different ethnic and racial groups in the United States. DESIGN: Collaborative
      Psychiatric Epidemiology Surveys (CPES) data were analyzed to calculate
      nationally representative estimates of depression care. SETTING: The 48
      coterminous United States. PARTICIPANTS: Household residents 18 years and older
      (N = 15 762) participated in the study. MAIN OUTCOME MEASURES: Past-year
      depression pharmacotherapy and psychotherapy using American Psychiatric
      Association guideline-concordant therapies. Depression severity was assessed with
      the Quick Inventory of Depressive Symptomatology Self-Report. Primary predictors
      were major ethnic/racial groups (Mexican American, Puerto Rican, Caribbean black,
      African American, and non-Latino white) and World Mental Health Composite
      International Diagnostic Interview criteria for 12-month major depressive
      episode. RESULTS: Mexican American and African American individuals meeting 12
      month major depression criteria consistently and significantly had lower odds for
      any depression therapy and guideline-concordant therapies despite depression
      severity ratings not significantly differing between ethnic/racial groups. All
      groups reported higher use of any past-year psychotherapy and guideline
      concordant psychotherapy compared with pharmacotherapy; however, Caribbean black
      and African American individuals reported the highest proportions of this use.
      CONCLUSIONS: Few Americans with recent major depression have used depression
      therapies and guideline-concordant therapies; however, the lowest rates of use
      were found among Mexican American and African American individuals. Ethnic/racial
      differences were found despite comparable depression care need. More Americans
      with recent major depression used psychotherapy over pharmacotherapy, and these
      differences were most pronounced among Mexican American and African American
      individuals. This report underscores the importance of disaggregating
      ethnic/racial groups and depression therapies in understanding and directing
      efforts to improve depression care in the United States.

PMID- 20048222
TI  - Incidence and risk patterns of anxiety and depressive disorders and
      categorization of generalized anxiety disorder.
AB  - CONTEXT: Controversy surrounds the diagnostic categorization of generalized
      anxiety disorder (GAD). OBJECTIVES: To examine the incidence, comorbidity, and
      risk patterns for anxiety and depressive disorders and to test whether
      developmental features of GAD more strongly support a view of this condition as a
      depressive as opposed to an anxiety disorder. DESIGN: Face-to-face, 10-year
      prospective longitudinal and family study with as many as 4 assessment waves. The
      DSM-IV Munich Composite International Diagnostic Interview was administered by
      clinically trained interviewers. SETTING: Munich, Germany. PARTICIPANTS: A
      community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34
      years at last follow-up. MAIN OUTCOME MEASURES: Cumulative incidence of GAD,
      other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic
      disorder), and depressive disorders (major depressive disorder, and dysthymia).
      RESULTS: Longitudinal associations between GAD and depressive disorders are not
      stronger than those between GAD and anxiety disorders or between other anxiety
      and depressive disorders. Survival analyses reveal that the factors associated
      with GAD overlap more strongly with those specific to anxiety disorders than
      those specific to depressive disorders. In addition, GAD differs from anxiety and
      depressive disorders with regard to family climate and personality profiles.
      CONCLUSIONS: Anxiety and depressive disorders appear to differ with regard to
      risk constellations and temporal longitudinal patterns, and GAD is a
      heterogeneous disorder that is, overall, more closely related to other anxiety
      disorders than to depressive disorders. More work is needed to elucidate the
      potentially unique aspects of pathways and mechanisms involved in the
      etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by
      cross-sectional features and diagnostic comorbidity patterns, minimizes the
      importance of longitudinal data on risk factors and symptom trajectories.

PMID- 20048223
TI  - Brain serotonin and dopamine transporter bindings in adults with high-functioning
      autism.
AB  - CONTEXT: Autism is a neurodevelopmental disorder that is characterized by
      repetitive and/or obsessive interests and behavior and by deficits in sociability
      and communication. Although its neurobiological underpinnings are postulated to
      lie in abnormalities of the serotoninergic and dopaminergic systems, the details
      remain unknown. OBJECTIVE: To determine the occurrence of changes in the binding
      of serotonin and dopamine transporters, which are highly selective markers for
      their respective neuronal systems. DESIGN: Using positron emission tomography, we
      measured the binding of brain serotonin and dopamine transporters in each
      individual with the radioligands carbon 11 ((11)C)-labeled trans-1,2,3,5,6,10
      beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN
      5652) and 2beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane ([(11)C]WIN-35,428),
      respectively. Statistical parametric mapping was used for between-subject
      analysis and within-subject correlation analysis with respect to clinical
      variables. SETTING: Participants recruited from the community. PARTICIPANTS:
      Twenty men (age range, 18-26 years; mean [SD] IQ, 99.3 [18.1]) with autism and 20
      age- and IQ-matched control subjects. RESULTS: Serotonin transporter binding was
      significantly lower throughout the brain in autistic individuals compared with
      controls (P < .05, corrected). Specifically, the reduction in the anterior and
      posterior cingulate cortices was associated with the impairment of social
      cognition in the autistic subjects (P < .05, corrected). A significant
      correlation was also found between repetitive and/or obsessive behavior and
      interests and the reduction of serotonin transporter binding in the thalamus (P <
      .05, corrected). In contrast, the dopamine transporter binding was significantly
      higher in the orbitofrontal cortex of the autistic group (P < .05, corrected in
      voxelwise analysis). In the orbitofrontal cortex, the dopamine transporter
      binding was significantly inversely correlated with serotonin transporter binding
      (r = -0.61; P = .004). CONCLUSIONS: The brains of autistic individuals have
      abnormalities in both serotonin transporter and dopamine transporter binding. The
      present findings indicate that the gross abnormalities in these neurotransmitter
      systems may underpin the neurophysiologic mechanism of autism. Our sample was not
      characteristic or representative of a typical sample of adults with autism in the
      community.

PMID- 20048224
TI  - Influence of environmental factors in higher risk of sudden infant death syndrome
      linked with parental mental illness.
AB  - CONTEXT: Since national risk reduction campaigns have been conducted, sudden
      infant death syndrome (SIDS) has become increasingly concentrated among
      disadvantaged families, including those affected by mental illness. However,
      causal mechanisms specific to this group are poorly understood. OBJECTIVES: To
      estimate relative risk and compare risk factor prevalence in infants with and
      without parental psychiatric inpatient history, and to explore effect
      modification after the 1992 Swedish risk reduction campaign. DESIGN: National
      birth cohort. Parental psychiatric admissions, maternal prenatal smoking,
      obstetric and social risk factors, and cause-specific infant death were
      ascertained via linkage between national registers. SETTING: The Swedish
      population, 1978 through 2004. PARTICIPANTS: All singleton live births (N = 2.5
      million). MAIN OUTCOME MEASURE: Incidence of SIDS. RESULTS: Risk of SIDS was
      higher with a history of parental inpatient care, especially if both parents were
      admitted with any mental illness (odds ratio, 6.8; 95% confidence interval, 4.7
      10.0), or if the mother (6.5; 4.9-8.7) or both parents (9.5; 5.5-16.4) had an
      alcohol/drug disorder. A 2-fold higher risk was also seen if the mother or father
      was admitted with any psychiatric illness other than alcohol or other drug
      disorders. Elevated risk persisted even if the last maternal inpatient episode
      had occurred 5 or more years before the infant's birth. After the national
      campaign, risk factor prevalence (especially maternal antenatal smoking) remained
      high in this population, and relative risks therefore increased. During 1992
      through 2004, smoking and individual social adversity measures jointly accounted
      for approximately half the excess risk linked with maternal psychiatric inpatient
      history, whereas the confounding effects of obstetric factors were minimal.
      CONCLUSIONS: Tailored approaches are needed to ensure that standard safety advice
      is effectively communicated to these vulnerable families. In particular, mentally
      ill pregnant women should be encouraged and better supported to stop smoking.
      Families with 2 affected parents require particularly strong support. A clearer
      understanding is needed as to why high risk factor prevalence persists among
      these parents.

PMID- 20048225
TI  - Structural differences in adult orbital and ventromedial prefrontal cortex
      predicted by infant temperament at 4 months of age.
AB  - CONTEXT: The term temperament refers to a biologically based predilection for a
      distinctive pattern of emotions, cognitions, and behaviors first observed in
      infancy or early childhood. High-reactive infants are characterized at age 4
      months by vigorous motor activity and crying in response to unfamiliar visual,
      auditory, and olfactory stimuli, whereas low-reactive infants show low motor
      activity and low vocal distress to the same stimuli. High-reactive infants are
      biased to become behaviorally inhibited in the second year of life, defined by
      timidity with unfamiliar people, objects, and situations. In contrast, low
      reactive infants are biased to develop into uninhibited children who
      spontaneously approach novel situations. OBJECTIVE: To examine whether
      differences in the structure of the ventromedial or orbitofrontal cerebral cortex
      at age 18 years are associated with high or low reactivity at 4 months of age.
      DESIGN: Structural magnetic resonance imaging in a cohort of 18-year-olds
      enrolled in a longitudinal study. Temperament was determined at 4 months of age
      by direct observation in the laboratory. SETTING: Athinoula A. Martinos Center
      for Biomedical Imaging, Massachusetts General Hospital. PARTICIPANTS: Seventy-six
      subjects who were high-reactive or low-reactive infants at 4 months of age. MAIN
      OUTCOME MEASURE: Cortical thickness. RESULTS: Adults with a low-reactive infant
      temperament, compared with those categorized as high reactive, showed greater
      thickness in the left orbitofrontal cortex. Subjects categorized as high reactive
      in infancy, compared with those previously categorized as low reactive, showed
      greater thickness in the right ventromedial prefrontal cortex. CONCLUSIONS: To
      our knowledge, this is the first demonstration that temperamental differences
      measured at 4 months of age have implications for the architecture of human
      cerebral cortex lasting into adulthood. Understanding the developmental
      mechanisms that shape these differences may offer new ways to understand mood and
      anxiety disorders as well as the formation of adult personality.

PMID- 20048226
TI  - Brief, personality-targeted coping skills interventions and survival as a non
      drug user over a 2-year period during adolescence.
AB  - CONTEXT: Selective interventions targeting personality risk are showing promise
      in the prevention of problematic drinking behavior, but their effect on illicit
      drug use has yet to be evaluated. OBJECTIVE: To investigate the efficacy of
      targeted coping skills interventions on illicit drug use in adolescents with
      personality risk factors for substance misuse. DESIGN: Randomized controlled
      trial. SETTING: Secondary schools in London, United Kingdom. PARTICIPANTS: A
      total of 5302 students were screened to identify 2028 students aged 13 to 16
      years with elevated scores on self-report measures of hopelessness, anxiety
      sensitivity, impulsivity, and sensation seeking. Seven hundred thirty-two
      students provided parental consent to participate in this trial. INTERVENTION:
      Participants were randomly assigned to a control no-intervention condition or a 2
      session group coping skills intervention targeting 1 of 4 personality profiles.
      MAIN OUTCOME MEASURES: The trial was designed and powered to primarily evaluate
      the effect of the intervention on the onset, prevalence, and frequency of illicit
      drug use over a 2-year period. RESULTS: Intent-to-treat repeated-measures
      analyses on continuous measures of drug use revealed time x intervention effects
      on the number of drugs used (P < .01) and drug use frequency (P < .05), whereby
      the control group showed significant growth in the number of drugs used as well
      as more frequent drug use over the 2-year period relative to the intervention
      group. Survival analysis using logistic regression revealed that the intervention
      was associated with reduced odds of taking up the use of marijuana (beta = -0.3;
      robust SE = 0.2; P = .09; odds ratio = 0.7; 95% confidence interval, 0.5-1.0),
      cocaine (beta = -1.4; robust SE = 0.4; P < .001; odds ratio = 0.2; 95% confidence
      interval, 0.1-0.5), and other drugs (beta = -0.7; robust SE = 0.3; P = .03; odds
      ratio = 0.5; 95% confidence interval, 0.3-0.9) over the 24-month period.
      CONCLUSION: This study extends the evidence that brief, personality-targeted
      interventions can prevent the onset and escalation of substance misuse in high
      risk adolescents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00344474.

PMID- 20048227
TI  - Psychological treatments of binge eating disorder.
AB  - CONTEXT: Interpersonal psychotherapy (IPT) is an effective specialty treatment
      for binge eating disorder (BED). Behavioral weight loss treatment (BWL) and
      guided self-help based on cognitive behavior therapy (CBTgsh) have both resulted
      in short-term reductions in binge eating in obese patients with BED. OBJECTIVE:
      To test whether patients with BED require specialty therapy beyond BWL and
      whether IPT is more effective than either BWL or CBTgsh in patients with a high
      negative affect during a 2-year follow-up. DESIGN: Randomized, active control
      efficacy trial. SETTING: University outpatient clinics. PARTICIPANTS: Two hundred
      five women and men with a body mass index between 27 and 45 who met DSM-IV
      criteria for BED. Intervention Twenty sessions of IPT or BWL or 10 sessions of
      CBTgsh during 6 months. MAIN OUTCOME MEASURES: Binge eating assessed by the
      Eating Disorder Examination. RESULTS: At 2-year follow-up, both IPT and CBTgsh
      resulted in greater remission from binge eating than BWL (P < .05; odds ratios:
      BWL vs CBTgsh, 2.3; BWL vs IPT, 2.6; and CBTgsh vs IPT, 1.2). Self-esteem (P <
      .05) and global Eating Disorder Examination (P < .05) scores were moderators of
      treatment outcome. The odds ratios for low and high global Eating Disorder
      Examination scores were 2.8 for BWL, 2.9 for CBTgsh, and 0.73 for IPT; for self
      esteem, they were 2.4 for BWL, 1.9 for CBTgsh, and 0.9 for IPT. CONCLUSIONS:
      Interpersonal psychotherapy and CBTgsh are significantly more effective than BWL
      in eliminating binge eating after 2 years. Guided self-help based on cognitive
      behavior therapy is a first-line treatment option for most patients with BED,
      with IPT (or full cognitive behavior therapy) used for patients with low self
      esteem and high eating disorder psychopathology. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00060762.

PMID- 20048228
TI  - IMAGE CARDIO MED: Two different mechanisms of myocardial ischemia involving 2
      separate myocardial segments in a patient with normal coronary angiography.

PMID- 20048229
TI  - Letter by Henrikson regarding article, "Endocarditis secondary to Microsporidia:
      giant vegetation in a pacemaker user".

PMID- 20048230
TI  - Letter by Paraskevas regarding article, "Risk factors for abdominal aortic
      aneurysms: a 7-year prospective study: the Tromso study".

PMID- 20048231
TI  - Letter by Goldstein et al regarding article, "Risk factors for abdominal aortic
      aneurysms: a 7-year prospective study: the Tromso study".

PMID- 20048233
TI  - Cardiovascular networks: systems-based approaches to cardiovascular disease.

PMID- 20048234
TI  - New P2Y(12) inhibitors.

PMID- 20048235
TI  - IMAGE CARDIO MED: Bronchocoronary collateral circulation: clinical utility of
      cardiac computed tomography.

PMID- 20048236
TI  - Long-term effects of prenatal and infancy nurse home visitation on the life
      course of youths: 19-year follow-up of a randomized trial.
AB  - OBJECTIVE: To examine the effect of prenatal and infancy nurse home visitation on
      the life course development of 19-year-old youths whose mothers participated in
      the program. DESIGN: Randomized trial. SETTING: Semirural community in New York.
      PARTICIPANTS: Three hundred ten youths from the 400 families enrolled in the
      Elmira Nurse-Family Partnership program. Intervention Families received a mean of
      9 home visits (range, 0-16) during pregnancy and 23 (range, 0-59) from birth
      through the child's second birthday. MAIN OUTCOME MEASURES: Youth self-reports of
      educational achievement, reproductive behaviors, welfare use, and criminal
      involvement. RESULTS: Relative to the comparison group, girls in the pregnancy
      and infancy nurse-visited group were less likely to have been arrested (10% vs
      30%; relative risk [RR], 0.33; 95% confidence interval [CI], 0.13-0.82) and
      convicted (4% vs 20%; 0.20; 0.05-0.85) and had fewer lifetime arrests (mean: 0.10
      vs 0.54; incidence RR [IRR], 0.18; 95% CI, 0.06-0.54) and convictions (0.04 vs
      0.37; 0.11; 0.02-0.51). Nurse-visited girls born to unmarried and low-income
      mothers had fewer children (11% vs 30%; RR, 0.35; 95% CI, 0.12-1.02) and less
      Medicaid use (18% vs 45%; 0.40; 0.18-0.87) than their comparison group
      counterparts. CONCLUSIONS: Prenatal and infancy home visitation reduced the
      proportion of girls entering the criminal justice system. For girls born to high
      risk mothers, there were additional positive program effects consistent with
      results from earlier phases of this trial. There were few program effects for
      boys.

PMID- 20048237
TI  - Reducing maternal intimate partner violence after the birth of a child: a
      randomized controlled trial of the Hawaii Healthy Start Home Visitation Program.
AB  - OBJECTIVES: To estimate whether home visitation beginning after childbirth was
      associated with changes in average rates of mothers' intimate partner violence
      (IPV) victimization and perpetration as well as rates of specific IPV types
      (physical assault, verbal abuse, sexual assault, and injury) during the 3 years
      of program implementation and during 3 years of long-term follow-up. DESIGN:
      Randomized controlled trial. SETTING: Oahu, Hawaii. PARTICIPANTS: Six hundred
      forty-three families with an infant at high risk for child maltreatment born
      between November 1994 and December 1995. Intervention Home visitors provided
      direct services and linked families to community resources. Home visits were to
      initially occur weekly and to continue for at least 3 years. MAIN OUTCOME
      MEASURES: Women's self-reports of past-year IPV victimization and perpetration
      using the Conflict Tactics Scale. Blinded research staff conducted maternal
      interviews following the child's birth and annually when children were aged 1 to
      3 years and then 7 to 9 years. RESULTS: During program implementation,
      intervention mothers as compared with control mothers reported lower rates of IPV
      victimization (incidence rate ratio [IRR], 0.86; 95% confidence interval [CI],
      0.73-1.01) and significantly lower rates of perpetration (IRR, 0.83; 95% CI, 0.72
      0.96). Considering specific IPV types, intervention women reported significantly
      lower rates of physical assault victimization (IRR, 0.85; 95% CI, 0.71-1.00) and
      perpetration (IRR, 0.82; 95% CI, 0.70-0.96). During long-term follow-up, rates of
      overall IPV victimization and perpetration decreased, with nonsignificant between
      group differences. Verbal abuse victimization rates (IRR, 1.14, 95% CI, 0.97
      1.34) may have increased among intervention mothers. CONCLUSION: Early-childhood
      home visitation may be a promising strategy for reducing IPV.

PMID- 20048239
TI  - Health care worker knowledge, attitudes, and beliefs regarding mandatory
      influenza vaccination.
AB  - OBJECTIVE: To determine the attitudes, beliefs, and knowledge of children's
      hospital health care workers toward mandatory influenza vaccination. DESIGN: Self
      administered, Web-based questionnaire. SETTING: A large, tertiary children's
      hospital. PARTICIPANTS: A random sample of 585 health care workers, including
      physicians, nurses, and all other hospital employees. Outcome Measure Attitudes
      of health care workers toward mandatory policies for annual influenza vaccination
      of health care workers as related to their opinions on safety, effectiveness, and
      knowledge about influenza and influenza vaccination. RESULTS: Many employees
      (70%) thought influenza vaccination should be mandatory for health care workers
      who did not have a medical contraindication. Nearly everyone, 363 of 391 (94%),
      who favored mandatory immunization had been immunized themselves. Of those who
      opposed mandatory immunization, 45 of 81 (55.6%) had been immunized (P < .001).
      Individuals who supported mandatory policies were more likely to believe that the
      vaccine is safe for both children and adults. There was no significant difference
      between the percentages of promandate and antimandate employees who believed
      influenza was dangerous for the patients where they work (66.5% and 62%,
      respectively, P = .07). Only 29% of antimandate employees believed they were at
      high risk of contracting influenza, compared with 51% of promandate employees (P
      < .001). CONCLUSIONS: Approval of mandatory influenza vaccine policies was high;
      however, attitudes about the dangers of influenza for patients were not
      associated with acceptance of mandatory vaccination policies for health care
      workers. Educational efforts targeting health care workers' fears and
      misconceptions about influenza vaccines might help to decrease the reservoir of
      unimmunized health care workers.

PMID- 20048238
TI  - Novel influenza A(H1N1) in a pediatric health care facility in New York City
      during the first wave of the 2009 pandemic.
AB  - OBJECTIVE: To describe the burden of care experienced by our pediatric health
      care facility in New York, New York, from May 3, 2009, to July 31, 2009, during
      the novel influenza A(H1N1) pandemic that began in spring 2009. DESIGN:
      Retrospective case series. SETTING: Pediatric emergency departments and inpatient
      facilities of New York-Presbyterian Hospital. Patients Children presenting to the
      emergency departments with influenza-like illness (ILI) and children aged 18
      years or younger hospitalized with positive laboratory test results for influenza
      A from May 3, 2009, to July 31, 2009. MAIN OUTCOME MEASURES: Proportion of
      children with ILI who were hospitalized and proportion of hospitalized children
      with influenza A with respiratory failure, bacterial superinfection, and
      mortality. RESULTS: When compared with the same period in 2008, the pediatric
      emergency departments experienced an excess of 3750 visits (19.9% increase).
      Overall, 27.7% of visits were for ILI; 2.5% of patients with ILI were
      hospitalized. Of the 115 hospitalized subjects with confirmed influenza A (median
      age, 4.3 years), 93 (80.9%) had underlying conditions. Four (3.5%) had identified
      bacterial superinfection, 1 (0.9%) died, and 35 (30.4%) were admitted to a
      pediatric intensive care unit; of these 35 patients, 11 had pneumonia and
      required mechanical ventilation, including high-frequency oscillatory ventilation
      (n = 3). CONCLUSIONS: At our center, 2.5% of children with ILI presenting to the
      emergency departments during the first wave of the 2009 novel influenza A(H1N1)
      pandemic were hospitalized. Of the 115 hospitalized children with confirmed
      influenza A, 9.6% had respiratory failure and 0.9% died. These findings can be
      compared with the disease severity of subsequent waves of the 2009 novel
      influenza A(H1N1) pandemic.

PMID- 20048240
TI  - Asthma care quality for children with minority-serving providers.
AB  - OBJECTIVE: To compare asthma care quality for children with and without minority
      serving providers. DESIGN: Cross-sectional telephone survey of parents, linked
      with a mailed survey of their children's providers. SETTING: A Medicaid
      predominant health plan and multispecialty provider group in Massachusetts.
      PARTICIPANTS: A total of 563 children with persistent asthma, identified by
      claims and encounter data. Main Exposure Whether the child's provider was
      minority serving (>25% of patients black or Latino). Outcomes Parent report of
      whether the child had (1) ever received inhaled steroids, (2) received influenza
      vaccination during the past season, and (3) received an asthma action plan in the
      past year. RESULTS: In unadjusted analyses, Latino children and those with
      minority-serving providers were more likely to have never received inhaled
      steroids. In adjusted models, the odds of never receiving inhaled steroids were
      not statistically significantly different for children with minority-serving
      providers (odds ratio [OR], 1.29; 95% confidence interval [CI], 0.63-2.64), or
      for Latino vs white children (OR, 1.76; 95% CI, 0.74-4.18); odds were increased
      for children receiving care in community health centers (OR, 4.88; 95% CI, 1.70
      14.02) or hospital clinics (OR, 4.53; 95% CI, 1.09-18.92) vs multispecialty
      practices. Such differences were not seen for influenza vaccinations or action
      plans. CONCLUSIONS: Children with persistent asthma are less likely to receive
      inhaled steroids if they receive care in community health centers or hospital
      clinics. Practice setting mediated initially observed disparities in inhaled
      steroid use by Latino children and those with minority-serving providers. No
      differences by race/ethnicity or minority-serving provider were observed for
      influenza vaccinations or asthma action plans.

PMID- 20048241
TI  - Sleep duration and hyperglycemia among obese and nonobese children aged 3 to 6
      years.
AB  - OBJECTIVE: To investigate the association between sleep duration and risk of
      hyperglycemia among preschool Chinese children. DESIGN: A population-based cross
      sectional study. SETTING: Seventy-one randomly selected kindergartens in Tianjin,
      China. PARTICIPANTS: Six hundred nineteen obese (body mass index z score > or
      =1.65) and 617 nonobese (body mass index z score <1.65) children aged 3 to 6
      years were recruited and matched by age. Main Exposure Sleep duration. MAIN
      OUTCOME MEASURES: Hyperglycemia, defined as a fasting glucose level of 100 mg/dL
      or higher. RESULTS: Obese children were more likely to have shorter sleep
      duration (< or =8 hours) compared with their nonobese counterparts (P < .001).
      Compared with those who slept for 9 or 10 hours per night, those who slept for 8
      hours or less had a significantly higher likelihood of having hyperglycemia,
      controlling for age and sex (odds ratio [OR], 1.65; 95% confidence interval [CI],
      1.12-2.45). After further adjustment for other potential confounders, the
      association still remained statistically significant (OR, 1.64; 95% CI, 1.09
      2.46). In the stratified multivariable analyses, those who were obese and slept
      for 8 hours or less had an increased risk of having hyperglycemia (OR, 2.12; 95%
      CI, 1.06-4.21) compared with those who were nonobese and slept for 9 hours or
      more. CONCLUSIONS: Shorter sleep duration is associated with an increased risk of
      having hyperglycemia among preschool Chinese children. Whether adequate sleep may
      help maintain euglycemia among children, especially for those who are overweight
      or obese, warrants further investigation.

PMID- 20048242
TI  - Childhood predictors of adult type 2 diabetes at 9- and 26-year follow-ups.
AB  - OBJECTIVE: To determine whether pediatric office measures (waist circumference,
      body mass index [BMI], systolic [SBP] and diastolic [DBP] blood pressure, and
      parental diabetes) and laboratory measures (glucose, triglyceride, high-density
      lipoprotein cholesterol, and insulin) predict risk of type 2 diabetes mellitus
      (T2DM) at ages 19 and 39 years. DESIGN: Nine- and 26-year prospective follow-ups
      of schoolchildren. SETTING: Urban and suburban schools. PARTICIPANTS: One
      thousand sixty-seven girls starting at age 10 years in the National Growth and
      Health Study and 822 schoolchildren aged 6 to 18 years at entry from the
      Princeton Follow-up Study. Outcome Measure Development of T2DM. RESULTS: In the
      Princeton Follow-up Study, childhood SBP and BMI in the top fifth percentile and
      black race predicted T2DM at age 39 years (area under the receiver-operator curve
      [AUC] = 0.698). Adding a childhood glucose level of 100 mg/dL or higher, and high
      density lipoprotein cholesterol in the bottom fifth percentile and triglyceride
      concentration in the top fifth percentile as explanatory variables increased AUC
      to 0.717 and 0.709, respectively. If childhood BMI, SBP, and DBP were all lower
      than the 75th percentile, likelihood of T2DM at age 39 years was 2%; the
      likelihood was 1% if the parents had no DM. In the National Growth and Heath
      Study, SBP in the top fifth percentile and parental diabetes predicted T2DM at
      age 19 years (AUC = 0.699). Adding insulin in the top fifth percentile increased
      AUC to 0.764, with insulin being a significant variable. If childhood BMI, SBP,
      and DBP were all lower than the 75th percentile, the likelihood of T2DM at age 19
      years was 0.2%, 0.2% if the parents were also free of DM, and 0.3% if childhood
      insulin was also less than the 75th percentile. CONCLUSIONS: Office-based
      childhood measures predict the presence and absence of future T2DM 9 and 26 years
      after baseline. Childhood insulin measurement improves prediction, facilitating
      approaches to primary prevention of T2DM.

PMID- 20048243
TI  - Survival sex work involvement as a primary risk factor for hepatitis C virus
      acquisition in drug-using youths in a canadian setting.
AB  - OBJECTIVE: To examine whether there were differential rates of hepatitis C virus
      (HCV) incidence in injecting drug-using youths who did and did not report
      involvement in survival sex work. DESIGN: Data were derived from 2 prospective
      cohort studies of injecting drug users (May 1, 1996, to July 31, 2007). Analyses
      were restricted to HCV antibody-negative youths who completed baseline and at
      least 1 follow-up assessment. SETTING: Vancouver, British Columbia, Canada.
      PARTICIPANTS: Of 3074 injecting drug users, 364 (11.8%) were youths (aged 14-24
      years) with a median age of 21.3 years and a duration of injecting drug use of 3
      years. Main Exposure Survival sex work involvement. MAIN OUTCOME MEASURE: The
      Kaplan-Meier method and Cox proportional hazards regression were used to compare
      HCV incidence among youths who did and did not report survival sex work. RESULTS:
      Baseline HCV prevalence was 51%, with youths involved in survival sex work
      significantly more likely to be HCV antibody positive (60% vs 44%; P = .002). In
      baseline HCV antibody-negative youths, the cumulative HCV incidence at 36 months
      was significantly higher in those involved in survival sex work (68.4% vs 38.8%;
      P < .001). The HCV incidence density was 36.8 (95% confidence interval [CI], 24.2
      53.5) per 100 person-years in youths reporting survival sex work involvement at
      baseline compared with 14.1 (9.4-20.3) per 100 person-years in youths not
      reporting survival sex work. In multivariate Cox proportional hazards analyses,
      survival sex work was the strongest predictor of elevated HCV incidence (adjusted
      relative hazard, 2.30; 95% CI, 1.27-4.15). CONCLUSION: This study calls attention
      to the critical need for evidence-based social and structural HCV prevention
      efforts that target youths engaged in survival sex work.

PMID- 20048244
TI  - Parental refusal of varicella vaccination and the associated risk of varicella
      infection in children.
AB  - OBJECTIVE: To quantify both the individual-level and attributable risk of
      varicella infection requiring medical care in children whose parents refuse
      varicella immunizations. DESIGN: Matched case-control study with conditional
      logistic regression analysis. SETTING: Kaiser Permanente of Colorado (KPCO)
      health plan between 1998 and 2008. PARTICIPANTS: Each pediatric physician
      diagnosed case of varicella (n = 133) was matched to 4 randomly selected controls
      (n = 493). Cases were matched by age, sex, and length of enrollment in KPCO. Main
      Exposures Varicella vaccine refusal. OUTCOME MEASURES: Varicella infection.
      RESULTS: There were 7 varicella vaccine refusers (5%) among the cases and 3
      (0.6%) among the controls. Children of parents who refused varicella
      immunizations were at a greatly increased risk of varicella infection requiring
      medical care (odds ratio, 8.6; 95% confidence interval, 2.2-33.3) compared with
      children of parents who accepted vaccinations (P = .004). In the entire KPCO
      pediatric population, 5% of varicella cases were attributed to parental vaccine
      refusal. CONCLUSIONS: Children of parents who refuse varicella immunizations are
      at high risk of varicella infection relative to vaccinated children. These
      results will be helpful to health care providers and parents when making
      decisions about immunizing children.

PMID- 20048245
TI  - Incidence and seasonality of hypothermia among newborns in southern Nepal.
AB  - OBJECTIVE: To quantify incidence, age distribution, and seasonality of neonatal
      hypothermia among a large population cohort. DESIGN: Longitudinal cohort study.
      SETTING: Sarlahi, Nepal. PARTICIPANTS: A total of 23 240 newborns born between
      September 2, 2002, and February 1, 2006. Main Exposures Community-based workers
      recorded axillary temperature on days 1 through 4, 6, 8, 10, 12, 14, 21, and 28
      (213 636 total measurements). MAIN OUTCOME MEASURES: Regression smoothing was
      used to describe axillary temperature patterns during the newborn period.
      Hypothermia incidence in the first day, week, and month were estimated using
      standard cutoffs. Ambient temperatures allowed comparison of mild hypothermia
      (36.0 degrees C to <36.5 degrees C) and moderate or severe hypothermia (<36.0
      degrees C) incidence over mean ambient temperature quintiles. RESULTS:
      Measurements lower than 36.5 degrees C were observed in 21 459 babies (92.3%);
      half (48.6%) had moderate or severe hypothermia, and risk peaked in the first 24
      to 72 hours of life. Risk of moderate or severe hypothermia increased by 41.3%
      (95% confidence interval, 40.0%-42.7%) for every 5 degrees C decrease in average
      ambient temperature. Relative to the highest quintile, risk was 4.03 (95%
      confidence interval, 3.77-4.30) times higher among babies exposed to the lowest
      quintile of average ambient temperature. In the hot season, one-fifth of the
      babies (18.2%) were observed below the moderate hypothermia cutoff. CONCLUSIONS:
      Mild or moderate hypothermia was nearly universal, with substantially higher risk
      in the cold season. However, incidence in the hot season was also high; thus,
      year-round thermal care promotion is required. Research on community, household,
      and caretaker practices associated with hypothermia can guide behavioral
      interventions to reduce risk.

PMID- 20048246
TI  - Male circumcision for the prevention of acquisition and transmission of sexually
      transmitted infections: the case for neonatal circumcision.
AB  - The American Academy of Pediatrics (AAP) male circumcision policy states that
      while there are potential medical benefits of newborn male circumcision, the data
      are insufficient to recommend routine neonatal circumcision. Since 2005, however,
      3 randomized trials have evaluated male circumcision for prevention of sexually
      transmitted infections. The trials found that circumcision decreases human
      immunodeficiency virus acquisition by 53% to 60%, herpes simplex virus type 2
      acquisition by 28% to 34%, and human papillomavirus prevalence by 32% to 35% in
      men. Among female partners of circumcised men, bacterial vaginosis was reduced by
      40%, and Trichomonas vaginalis infection was reduced by 48%. Genital ulcer
      disease was also reduced among males and their female partners. These findings
      are also supported by observational studies conducted in the United States. The
      AAP policy has a major impact on neonatal circumcision in the United States. This
      review evaluates the recent data that support revision of the AAP policy to fully
      reflect the evidence of long-term health benefits of male circumcision.

PMID- 20048247
TI  - Interventions for reducing adolescent alcohol abuse: a meta-analytic review.
AB  - OBJECTIVE: To assess the effectiveness of substance abuse interventions for their
      ability to reduce adolescent alcohol use. DATA SOURCES: MEDLINE; PsycINFO; ERIC;
      Wilson Social Science Abstracts; Criminal Justice Abstracts; Social Work
      Abstracts; Social Science Citation Index; Dissertations Abstracts International;
      National Criminal Justice Research Service; Social, Psychological,
      Criminological, Educational Trials Register; and the PsiTri databases from 1960
      through 2008. STUDY SELECTION: Of 64 titles and abstracts identified, 16 studies
      and 26 outcomes constituted the sample. The researchers calculated Hedges g
      effect sizes and used a random-effects model to calculate adjusted pooled effect
      sizes. Heterogeneity was explored using stratified analyses. Main Exposure
      Completion of a substance abuse intervention that aimed to reduce or eliminate
      alcohol consumption. MAIN OUTCOME MEASURES: Abstinence, frequency of alcohol use,
      and quantity of alcohol use measured between 1 month and 1 year upon completion
      of treatment. RESULTS: Pooled effects of standardized mean differences indicate
      that interventions significantly reduce adolescent alcohol use (Hedges g = -0.61;
      95% confidence interval [CI], -0.83 to -0.40). Stratified analyses revealed
      larger effects for individual treatment (Hedges g = -0.75; 95% CI, -1.05 to 
      0.40) compared with family-based treatments (Hedges g = -0.46; 95% CI, -0.66 to 
      0.26). CONCLUSIONS: Treatments for adolescent substance abuse appear to be
      effective in reducing alcohol use. Individual-only interventions had larger
      effect sizes than family-based interventions and effect sizes decreased as length
      of follow-up increased. Furthermore, behavior-oriented treatments demonstrated
      promise in attaining long-term effects.

PMID- 20048248
TI  - Broadening understanding of the long-term effects of risk- and protection-focused
      prevention on the public health: lessons from nurse-family partnerships.

PMID- 20048249
TI  - Newborn circumcision: routine or not routine, that is the question.

PMID- 20048250
TI  - Picture of the month: adrenoleukodystrophy and adrenomyeloneuropathy.

PMID- 20048251
TI  - Historical trends in low birth weight.

PMID- 20048252
TI  - Risk of parental dissolution of partnership following the loss of a child to
      cancer: a population-based long-term follow-up.

PMID- 20048253
TI  - Advice for patients: Male circumcision: new information about health benefits.

PMID- 20048254
TI  - Are you being served?

PMID- 20048255
TI  - It's the data!
AB  - Three articles from the early years of Molecular Biology of the Cell (MBoC) have
      had remarkably many citations in the literature since their publication
      approximately 10 years ago. As a coauthor of these articles and the former editor
      of MBoC, I was asked for possible explanations. I believe the answer lies in the
      unusual nature of these articles: each presents and summarizes gene expression
      data for nearly every gene in the yeast or human genomes. Continuing interest in
      the data themselves by cell biologists, rather than results or conclusions drawn
      by the authors, best accounts for the citation history. The flatness of the
      numbers of citations over time, the continuing high rate of accesses to
      individual Web sites set up to allow searching and display of the underlying
      data, and the large fraction of citations in journals focused on mathematics and
      computation all support the same conclusion: it's the data.

PMID- 20048256
TI  - A tale of mother and daughter.
AB  - Loving science and nature and being a scientist can be very different, yet the
      two are so intertwined in a scientist's life that you will certainly experience
      both aspects. This essay presents my perspective on how, as one who loves science
      and nature, I came to fall in love with centrosome behavior in stem cells and how
      I came to run a lab as a scientist. When I started, there was a big gap between
      my love for science and my experience as a scientist. I filled this gap by
      learning a "laid-back confidence."

PMID- 20048257
TI  - A developmental journey and lessons learned along the way.
AB  - A career in science is a journey of wonder and discovery. To succeed in science
      requires curiosity, perseverance, a good dose of luck, and wise guidance from
      those who have taken the journey ahead of you. We also need to use our science
      skills to contribute to public debate on complex issues of the day.

PMID- 20048258
TI  - It's a wonderful life: a career as an academic scientist.
AB  - Many years of training are required to obtain a job as an academic scientist. Is
      this investment of time and effort worthwhile? My answer is a resounding "yes."
      Academic scientists enjoy tremendous freedom in choosing their research and
      career path, experience unusual camaraderie in their lab, school, and
      international community, and can contribute to and enjoy being part of this
      historical era of biological discovery. In this essay, I further elaborate by
      listing my top ten reasons why an academic job is a desirable career for young
      people who are interested in the life sciences.

PMID- 20048259
TI  - Walking along the serendipitous path of discovery.
AB  - Deciphering of the molecular mechanism of the "unfolded protein response" (UPR)
      provides a wonderful example of how serendipity can shape scientific discovery.
      Secretory and membrane proteins begin their journey to the cell surface in the
      endoplasmic reticulum (ER). Before leaving the organelle, proteins are quality
      controlled, and only properly folded proteins are transported onwards. The UPR
      detects an insufficiency in the protein-folding capacity in the ER and in the
      ways of a finely tuned homeostat adjusts organelle abundance according to need.
      If the protein-folding defect in the ER cannot be corrected, the UPR switches
      from a cell-protective to a cell-destructive mode and activates apoptosis in
      metazoan cells. Such life or death decisions position the UPR in the center of
      numerous pathologies, including viral infection, protein-folding diseases,
      diabetes, and cancer. The UPR proved to be a rich field for serendipitous
      discovery because the molecular machines that transmit information about
      insufficient protein folding and activate appropriate gene expression programs
      function in unusual, unprecedented ways. A key regulatory switch in the UPR, for
      example, is a cytoplasmic, nonconventional mRNA spicing reaction, initiated by a
      bifunctional transmembrane kinase/endoribonuclease.

PMID- 20048261
TI  - Recreation of the terminal events in physiological integrin activation.
AB  - Increased affinity of integrins for the extracellular matrix (activation)
      regulates cell adhesion and migration, extracellular matrix assembly, and
      mechanotransduction. Major uncertainties concern the sufficiency of talin for
      activation, whether conformational change without clustering leads to activation,
      and whether mechanical force is required for molecular extension. Here, we
      reconstructed physiological integrin activation in vitro and used cellular,
      biochemical, biophysical, and ultrastructural analyses to show that talin binding
      is sufficient to activate integrin alphaIIbbeta3. Furthermore, we synthesized
      nanodiscs, each bearing a single lipid-embedded integrin, and used them to show
      that talin activates unclustered integrins leading to molecular extension in the
      absence of force or other membrane proteins. Thus, we provide the first proof
      that talin binding is sufficient to activate and extend membrane-embedded
      integrin alphaIIbbeta3, thereby resolving numerous controversies and enabling
      molecular analysis of reconstructed integrin signaling.

PMID- 20048262
TI  - Activation of Cdc6 by MyoD is associated with the expansion of quiescent myogenic
      satellite cells.
AB  - MyoD is a transcriptional factor that is required for the differentiation of
      muscle stem cells (satellite cells). In this study, we describe a previously
      unknown function for MyoD in regulating a gene (Cdc6) that is vital to endowing
      chromatin with the capability of replicating DNA. In C2C12 and primary mouse
      myoblasts, we show that MyoD can occupy an E-box within the promoter of Cdc6 and
      that this association, along with E2F3a, is required for its activity. MyoD and
      Cdc6 are both expressed after quiescent C2C12 myoblasts or satellite cells in
      association with myofibers are stimulated for growth, but MyoD appears at least 2
      3 h earlier than Cdc6. Finally, knockdown of MyoD impairs the ability of C2C12
      cells to express Cdc6 after leaving quiescence, and as a result, they cannot
      fully progress into S phase. Our results define a mechanism by which MyoD helps
      myogenic satellite cells to enter into the first round of DNA replication after
      transitioning out of quiescence.

PMID- 20048263
TI  - The cytoplasmic tail of fibrocystin contains a ciliary targeting sequence.
AB  - Sensory functions of primary cilia rely on ciliary-localized membrane proteins,
      but little is known about how these receptors are targeted to the cilium. To
      further our understanding of this process, we dissected the ciliary targeting
      sequence (CTS) of fibrocystin, the human autosomal recessive polycystic kidney
      disease gene product. We show that the fibrocystin CTS is an 18-residue motif
      localized in the cytoplasmic tail. This motif is sufficient to target green
      fluorescent protein (GFP) to cilia of ciliated cells and targets GFP to lipid
      rafts if the cells are not ciliated. Rab8, but not several other Rabs implicated
      in ciliary assembly, binds to the CTS in a coimmunoprecipitation assay. Dominant
      negative Rab8 interacts more strongly than wild-type or constitutively active
      Rab8, and coexpression of this dominant-negative mutant Rab8 blocks trafficking
      to the cilium. This suggests that the CTS functions by binding regulatory
      proteins like Rab8 to control trafficking through the endomembrane system and on
      to the cilium.

PMID- 20048264
TI  - Summaries for patients. Smoking, quitting smoking, and the risk for type 2
      diabetes.

PMID- 20048265
TI  - Summaries for patients. Adherence to HIV treatment and costs of care.

PMID- 20048266
TI  - In clinic. Diabetic ketoacidosis.
AB  - This issue provides a clinical overview of diabetic ketoacidosis focusing on
      prevention, diagnosis, treatment, practice improvement, and patient information.
      Readers can complete the accompanying CME quiz for 1.5 credits. Only ACP members
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      are interested in these primary resources for more detail can consult
      www.acponline.org, http://pier.acponline.org, and other resources referenced
      within each issue of In the Clinic.

PMID- 20048268
TI  - Association of antiretroviral therapy adherence and health care costs.
AB  - BACKGROUND: Antiretroviral therapy (ART) adherence predicts HIV disease
      progression and survival, but its effect on direct health care costs is unclear.
      OBJECTIVE: To determine the effect of ART adherence on direct health care costs
      among adults in a resource-limited setting. DESIGN: Cohort study. SETTING: Aid
      for AIDS, a private-sector disease management program in South Africa. PATIENTS:
      6833 HIV-infected adults who started ART between 6 August 2000 and 30 April 2006.
      MEASUREMENTS: Monthly direct health care costs authorized by Aid for AIDS were
      averaged over all months. Pharmacy claim adherence, expressed as a percentage,
      was categorized into quartiles, from 1 (lowest) to 4 (highest). Effects of
      covariates on monthly total costs were assessed with a 2-step model with logit
      for probability of nonzero costs and a generalized linear model (GLM). RESULTS:
      Total mean monthly costs were $370 (SD, $644). Mean monthly costs of ART were $32
      (SD, $18); hospitalizations, $151 (SD, $436); consultations, $76 (SD, $66);
      investigations, $37 (SD, $50); and non-ART medications, $53 (SD, $180). Total
      mean monthly costs ranged from $313 (SD, $598) for quartile 4 to $376 (SD, $657)
      for quartile 1. Hospitalization costs increased from 29% to 51% of total costs as
      adherence decreased. In the GLM 2-step model, moving from adherence quartile 1 to
      quartile 2, 3, or 4 increased the probability of having nonzero total monthly
      costs by 0.078, 0.15, and 0.21 percentage point, respectively (P < 0.001). For
      patients with nonzero costs, increasing adherence from quartile 1 to quartile 2,
      3, or 4 decreased total monthly costs by $70, $133, and $192, respectively (P <
      0.001). Moving from adherence quartiles 1 to 4 had the highest decrease in net
      overall median monthly health care costs (-$85 [interquartile range, -$116 to 
      $41]). LIMITATIONS: Indirect health care costs were not included. Experience may
      not reflect that of public HIV/AIDS programs. CONCLUSION: High ART adherence was
      associated with lower mean monthly direct health care costs, particularly reduced
      hospitalization costs, in this South African HIV cohort.

PMID- 20048267
TI  - Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort
      study.
AB  - BACKGROUND: Cigarette smoking is an established predictor of incident type 2
      diabetes mellitus, but the effects of smoking cessation on diabetes risk are
      unknown. OBJECTIVE: To test the hypothesis that smoking cessation increases
      diabetes risk in the short term, possibly owing to cessation-related weight gain.
      DESIGN: Prospective cohort study. SETTING: The ARIC (Atherosclerosis Risk in
      Communities) Study. PATIENTS: 10,892 middle-aged adults who initially did not
      have diabetes in 1987 to 1989. MEASUREMENTS: Smoking was assessed by interview at
      baseline and at subsequent follow-up. Incident diabetes was ascertained by
      fasting glucose assays through 1998 and self-report of physician diagnosis or use
      of diabetes medications through 2004. RESULTS: During 9 years of follow-up, 1254
      adults developed type 2 diabetes. Compared with adults who never smoked, the
      adjusted hazard ratio of incident diabetes in the highest tertile of pack-years
      was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults
      quit smoking. After adjustment for age, race, sex, education, adiposity, physical
      activity, lipid levels, blood pressure, and ARIC Study center, compared with
      adults who never smoked, the hazard ratios of diabetes among former smokers, new
      quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to
      2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight
      change and leukocyte count attenuated these risks substantially. In an analysis
      of long-term risk after quitting, the highest risk occurred in the first 3 years
      (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12
      years. LIMITATION: Residual confounding is possible even with meticulous
      adjustment for established diabetes risk factors. CONCLUSION: Cigarette smoking
      predicts incident type 2 diabetes, but smoking cessation leads to higher short
      term risk. For smokers at risk for diabetes, smoking cessation should be coupled
      with strategies for diabetes prevention and early detection.

PMID- 20048269
TI  - Systematic review: prediction of perioperative cardiac complications and
      mortality by the revised cardiac risk index.
AB  - BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to predict
      perioperative cardiac complications. PURPOSE: To evaluate the ability of the RCRI
      to predict cardiac complications and death after noncardiac surgery. DATA
      SOURCES: MEDLINE, EMBASE, and ISI Web of Science (1966 to 31 December 2008).
      STUDY SELECTION: Cohort studies that reported the association of the RCRI with
      major cardiac complications (cardiac death, myocardial infarction, and nonfatal
      cardiac arrest) or death in the hospital or within 30 days of surgery. DATA
      EXTRACTION: Two reviewers independently extracted study characteristics,
      documented outcome data, and evaluated study quality. DATA SYNTHESIS: Of 24
      studies (792 740 patients), 18 reported cardiac complications; 6 of the 18
      studies were prospective and had uniform outcome surveillance and blinded outcome
      adjudication. The RCRI discriminated moderately well between patients at low
      versus high risk for cardiac events after mixed noncardiac surgery (area under
      the receiver-operating characteristic curve [AUC], 0.75 [95% CI, 0.72 to 0.79]);
      sensitivity, 0.65 [CI, 0.46 to 0.81]; specificity, 0.76 [CI, 0.58 to 0.88];
      positive likelihood ratio, 2.78 [CI, 1.74 to 4.45]; negative likelihood ratio,
      0.45 [CI, 0.31 to 0.67]). Prediction of cardiac events after vascular noncardiac
      surgery was less accurate (AUC, 0.64 [CI, 0.61 to 0.66]; sensitivity, 0.70 [CI,
      0.53 to 0.82]; specificity, 0.55 [CI, 0.45 to 0.66]; positive likelihood ratio,
      1.56 [CI, 1.42 to 1.73]; negative likelihood ratio, 0.55 [CI, 0.40 to 0.76]). Six
      studies reported death, with a median AUC of 0.62 (range, 0.54 to 0.78). A pooled
      AUC for predicting death could not be calculated because of very high
      heterogeneity (I(2) = 95%). LIMITATION: Studies generally were of low
      methodological quality, had varied definitions of cardiac events, and were
      statistically and clinically heterogeneous. CONCLUSION: The RCRI discriminated
      moderately well between patients at low versus high risk for cardiac events after
      mixed noncardiac surgery. It did not perform well at predicting cardiac events
      after vascular noncardiac surgery or at predicting death. High-quality research
      is needed in this area of perioperative medicine.

PMID- 20048270
TI  - Recommended adult immunization schedule: United States, 2010.

PMID- 20048271
TI  - Cultural competency training and performance reports to improve diabetes care for
      black patients: a cluster randomized, controlled trial.
AB  - BACKGROUND: Increasing clinician awareness of racial disparities and improving
      communication may enhance diabetes care among black patients. OBJECTIVE: To
      evaluate the effect of cultural competency training and performance feedback for
      primary care clinicians on diabetes care for black patients. DESIGN: Cluster
      randomized, controlled trial conducted between June 2007 and May 2008.
      (ClinicalTrials.gov registration number: NCT00436176) SETTING: 8 ambulatory
      health centers in eastern Massachusetts. PARTICIPANTS: 124 primary care
      clinicians caring for 2699 (36%) black and 4858 (64%) white diabetic patients.
      INTERVENTION: INTERVENTION clinicians received cultural competency training and
      monthly race-stratified performance reports that highlighted racial differences
      in control of hemoglobin A(1c) (HbA(1c)) and low-density lipoprotein (LDL)
      cholesterol levels and blood pressure. MEASUREMENTS: Clinician awareness of
      racial differences in diabetes care and rates of achieving clinical control
      targets among black patients at 12 months. RESULTS: White and black patients
      differed significantly in baseline rates of achieving an HbA(1c) level less than
      7% (46% vs. 40%), an LDL cholesterol level less than 2.59 mmol/L (<100 mg/dL)
      (55% vs. 43%), and blood pressure less than 130/80 mm Hg (32% vs. 24%) (all P <
      0.050). At study completion, intervention clinicians were significantly more
      likely than control clinicians to acknowledge the presence of racial disparities
      in the 8 health centers as a whole (82% vs. 59%; P = 0.003), within their local
      health center (70% vs. 51%; P = 0.020), and among their own patients (63% vs.
      43%; P = 0.037). Black patients of clinicians in the intervention and control
      groups did not differ at 12 months in rates of controlling HbA(1c) level (48% vs.
      45%; P = 0.24), LDL cholesterol level (48% vs. 49%; P = 0.40), or blood pressure
      (23% vs. 25%; P = 0.47). LIMITATION: 11% of primary care teams did not attend
      cultural competency training sessions. CONCLUSION: The combination of cultural
      competency training and race-stratified performance reports increased clinician
      awareness of racial disparities in diabetes care but did not improve clinical
      outcomes among black patients.

PMID- 20048272
TI  - Spending more to save more: interventions to promote adherence.

PMID- 20048273
TI  - The revised cardiac risk index delivers what it promised.

PMID- 20048274
TI  - Adult immunization guidelines: challenges and opportunities.

PMID- 20048275
TI  - Why geriatrics?

PMID- 20048276
TI  - Advice.

PMID- 20048277
TI  - Concerns about meta-analysis of glucose control and cardiovascular disease in
      type 2 diabetes.

PMID- 20048278
TI  - Pulse versus daily oral cyclophosphamide in ANCA-associated vasculitis.

PMID- 20048279
TI  - Pulse versus daily oral cyclophosphamide in ANCA-associated vasculitis.

PMID- 20048280
TI  - Glycemic control in the intensive care unit.

PMID- 20048281
TI  - Pulse versus daily oral cyclophosphamide in ANCA-associated vasculitis.

PMID- 20048282
TI  - Spoons systematically bias dosing of liquid medicine.

PMID- 20048284
TI  - Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying
      the active site of AID.
AB  - High-affinity antibodies are generated by somatic hypermutation with nucleotide
      substitutions introduced into the IgV in a semirandom fashion, but with intrinsic
      mutational hotspots strategically located to optimize antibody affinity
      maturation. The process is dependent on activation-induced deaminase (AID), an
      enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is
      sensitive to the identity of the 5'-flanking nucleotide. As a critical test of
      whether such DNA deamination activity underpins antibody diversification and to
      gain insight into the extent to which the antibody mutation spectrum is dependent
      on the intrinsic substrate specificity of AID, we investigated whether it is
      possible to change the IgV mutation spectrum by altering AID's active site such
      that it prefers a pyrimidine (rather than a purine) flanking the targeted
      deoxycytidine. Consistent with the DNA deamination mechanism, B cells expressing
      the modified AID proteins yield altered IgV mutation spectra (exhibiting a purine
      ->pyrimidine shift in flanking nucleotide preference) and altered hotspots.
      However, AID-catalyzed deamination of IgV targets in vitro does not yield the
      same degree of hotspot dominance to that observed in vivo, indicating the
      importance of features beyond AID's active site and DNA local sequence
      environment in determining in vivo hotspot dominance.

PMID- 20048285
TI  - B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for
      establishing long-lived antibody responses in humans.
AB  - Engagement of cytokine receptors by specific ligands activate Janus kinase-signal
      transducer and activator of transcription (STAT) signaling pathways. The exact
      roles of STATs in human lymphocyte behavior remain incompletely defined.
      Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent
      regulator of B cell differentiation. We have studied patients with inactivating
      mutations in STAT1 or STAT3 to dissect their contribution to B cell function in
      vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the
      number of functional, antigen (Ag)-specific memory B cells and abolished the
      ability of IL-21 to induce naive B cells to differentiate into plasma cells
      (PCs). This resulted from impaired activation of the molecular machinery required
      for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell
      formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3
      plays a critical role in generating effector B cells from naive precursors in
      humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific
      humoral immune responses and provide a mechanism for the functional antibody
      deficit in STAT3-deficient patients.

PMID- 20048286
TI  - Heterozygous deficiency of delta-catenin impairs pathological angiogenesis.
AB  - Vascular and neuronal networks share a similar branching morphology, and emerging
      evidence implicates common mechanisms in the formation of both systems. delta
      Catenin is considered a neuronal catenin regulating neuron cell-cell adhesion and
      cell motility. Here, we report expression of delta-catenin in vascular
      endothelium, and show that deletion of only one allele of delta-catenin is
      sufficient to impair endothelial cell motility and vascular assembly in vitro and
      pathological angiogenesis in vivo, thereby inhibiting tumor growth and wound
      healing. In contrast, deletion of one or both allele of delta-catenin had no
      effects on hormone-induced physiological angiogenesis in the uterus. Molecular
      analysis confirmed a gene dosage effect of delta-catenin on Rho GTPase activity.
      Moreover, we show that inflammatory cytokines, but not angiogenic factors,
      regulate delta-catenin expression, and the levels of delta-catenin positively
      correlate to human lung cancers. Collectively, our data suggest that
      inflammation, commonly associated with disease conditions, induces delta-catenin
      expression that specifically regulates pathological, and not physiological,
      angiogenesis. Because only pathological angiogenesis is sensitive to decreased
      levels of delta-catenin, this may provide a good target for antiangiogenic
      therapy.

PMID- 20048288
TI  - Remote sensing of soil degradation: introduction.
AB  - In the 21st century, mapping and monitoring the occurrence of soil degradation
      will be an important component of successful land management. Remote sensing,
      with its unique ability to measure across space and time, will be an increasingly
      indispensible tool for assessing degradation. However, much of the recent
      experience and progress in using remote sensing and other geospatial technologies
      to map soil degradation is reported outside of the peer-reviewed literature. This
      motivated the organization of a special collection of papers focused on remote
      sensing of soil degradation, to highlight recent successes, common challenges,
      and promising new approaches. This introductory paper provides an overview of the
      papers, gaps in knowledge, and future research directions. Across several regions
      and types of degradation, many assessments to date have relied heavily on data
      from the Landsat satellite sensor. Many approaches have also relied at some point
      on subjective visual interpretation, either of the satellite imagery itself or to
      provide field data used to train models that use satellite data. While
      subjectivity is not necessarily bad, it precludes repeatability and makes it even
      more important to rigorously test model estimates with independent data. Overall,
      it remains quite challenging to find robust relationships between remote sensing
      measures and soil degradation, particularly for slight to moderate levels of
      degradation. There have nonetheless been some clear successes, and there remains
      great potential for progress. Promising directions outlined in the papers include
      using multi-year measures of vegetation condition, combining different sensor
      systems including optical and radar data, and using advanced statistical
      techniques such as Bayesian networks and decision trees.

PMID- 20048289
TI  - Remote sensing and geographic information system for appraisal of salt-affected
      soils in India.
AB  - Quantification of the nature, extent, and spatial distribution of salt-affected
      soils (SAS) for India and the world is essential for planning and implementing
      reclamation programs in a timely and cost-effective manner for sustained crop
      production. The national extent of SAS for India over the last four decades was
      assessed by conventional and remote sensing approaches using diverse
      methodologies and class definitions and ranged from 6.0 to 26.1 million hectares
      (Mha) and 1.2 to 10.1 Mha, respectively. In 1966, an area of 6 Mha under SAS was
      first reported using the former approach. Three national estimates, obtained
      using remote sensing, were reconciled using a geographic information system,
      resulting in an acceptable extent of 6.73 Mha. Moderately and severely salt
      encrusted lands having large contiguous area have been correctly mapped, but
      slightly salt-encrusted land having smaller affected areas within croplands has
      not been accurately mapped. Recent satellite sensors (e.g., Resourcesat-1,
      Cartosat-2, IKONOS-II, and RISAT-2), along with improved image processing
      techniques integrated with terrain and other spatial data using a geographic
      information system, are enabling mapping at large scale. Significant variations
      in salt encrustation at the surface caused by soil moisture, waterlogging
      conditions, salt-tolerant crops, and dynamics of subsurface salts present
      constraints in appraisal, delineation, and mapping efforts. The article provides
      an overview of development, identification, characterization, and delineation of
      SAS, past and current national scenarios of SAS using conventional and remote
      sensing approaches, reconciliation of national estimates, issues of SAS mapping,
      and future scope.

PMID- 20048290
TI  - Salinity monitoring in Western Australia using remotely sensed and other spatial
      data.
AB  - The southwest of Western Australia is affected by dryland salinity that results
      in the loss of previously productive agricultural land, damage to buildings,
      roads, and other infrastructure, decline in pockets of remnant vegetation and
      biodiversity, and reduction in water quality. Accurate information on the
      location and rate of change of the extent of saline land over the region is
      required by resource managers. For the first time, comprehensive, spatially
      explicit maps of dryland salinity and its change over approximately 10 yr for the
      southwest agricultural region of Western Australia have been produced
      operationally in the 'Land Monitor' project. The methods rely on an integrated
      analysis of long-term sequences of Landsat TM satellite image data together with
      variables derived from digital elevation models (DEMs). Understanding of the
      physical process and surface expression of salinity provided by experts was used
      to guide the analyses. Ground data-the delineation of salt-affected land by field
      experts-was collected for training and validation. The results indicate that the
      land area currently affected by salinity in Western Australia's southwest is
      about 1 million hectares (in 1996) and the annual rate of increase is about
      14,000 ha. This is a lesser extent than many previous estimates and lower rate of
      change than generally predicted from limited hydrological data. The results are
      widely distributed and publicly available. The key to providing accurate mapping
      and monitoring information was the incorporation of time series classification of
      a sequence of images over several years combined with landform information.

PMID- 20048291
TI  - A methodology to estimate the future extent of dryland salinity in the southwest
      of Western Australia.
AB  - In the southwestern agricultural region of Western Australia, the clearing of the
      original perennial vegetation for annual vegetation-based dryland agriculture has
      lead to rising saline groundwater levels. This has had effects such as reduced
      productivity of agricultural land, death of native vegetation, reduced stream
      water quality and infrastructure damage. These effects have been observed at many
      locations within the 18 million ha of cleared land. This has lead to efforts to
      quantify, in a spatially explicit way, the historical and likely future extent of
      the area affected, with the view to informing management decisions. This study
      was conducted to determine whether the likely future extent of the area affected
      by dryland salinity could be estimated by means of developing spatially explicit
      maps for use in management and planning. We derived catchment-related variables
      from digital elevation models and perennial vegetation presence/absence maps. We
      then used these variables to predict the salinity hazard extent by applying a
      combination of decision tree classification and morphological image processing
      algorithms. Sufficient objective data such as groundwater depth, its rate of
      rise, and its concentration of dissolved salts were generally not available, so
      we used regional expert opinion (derived from the limited existing studies on
      salinity hazard extent) as training and validation data. We obtained an 87%
      agreement in the salinity hazard extent estimated by this method compared with
      the validation data, and conclude that the maps are sufficient for planning. We
      estimate that the salinity hazard extent is 29.7% of the agricultural land.

PMID- 20048292
TI  - Regional-scale assessment of soil salinity in the Red River Valley using multi
      year MODIS EVI and NDVI.
AB  - The ability to inventory and map soil salinity at regional scales remains a
      significant challenge to scientists concerned with the salinization of
      agricultural soils throughout the world. Previous attempts to use satellite or
      aerial imagery to assess soil salinity have found limited success in part because
      of the inability of methods to isolate the effects of soil salinity on vegetative
      growth from other factors. This study evaluated the use of Moderate Resolution
      Imaging Spectroradiometer (MODIS) imagery in conjunction with directed soil
      sampling to assess and map soil salinity at a regional scale (i.e., 10-10(5)
      km(2)) in a parsimonious manner. Correlations with three soil salinity ground
      truth datasets differing in scale were made in Kittson County within the Red
      River Valley (RRV) of North Dakota and Minnesota, an area where soil salinity
      assessment is a top priority for the Natural Resource Conservation Service
      (NRCS). Multi-year MODIS imagery was used to mitigate the influence of temporally
      dynamic factors such as weather, pests, disease, and management influences. The
      average of the MODIS enhanced vegetation index (EVI) for a 7-yr period exhibited
      a strong relationship with soil salinity in all three datasets, and outperformed
      the normalized difference vegetation index (NDVI). One-third to one-half of the
      spatial variability in soil salinity could be captured by measuring average MODIS
      EVI and whether the land qualified for the Conservation Reserve Program (a USDA
      program that sets aside marginally productive land based on conservation
      principles). The approach has the practical simplicity to allow broad application
      in areas where limited resources are available for salinity assessment.

PMID- 20048293
TI  - Remote sensing of land degradation: experiences from Latin America and the
      Caribbean.
AB  - Land degradation caused by deforestation, overgrazing, and inappropriate
      irrigation practices affects about 16% of Latin America and the Caribbean (LAC).
      This paper addresses issues related to the application of remote sensing
      technologies for the identification and mapping of land degradation features,
      with special attention to the LAC region. The contribution of remote sensing to
      mapping land degradation is analyzed from the compilation of a large set of
      research papers published between the 1980s and 2009, dealing with water and wind
      erosion, salinization, and changes of vegetation cover. The analysis undertaken
      found that Landsat series (MSS, TM, ETM+) are the most commonly used data source
      (49% of the papers report their use), followed by aerial photographs (39%), and
      microwave sensing (ERS, JERS-1, Radarsat) (27%). About 43% of the works analyzed
      use multi-scale, multi-sensor, multi-spectral approaches for mapping degraded
      areas, with a combination of visual interpretation and advanced image processing
      techniques. The use of more expensive hyperspectral and/or very high spatial
      resolution sensors like AVIRIS, Hyperion, SPOT-5, and IKONOS tends to be limited
      to small surface areas. The key issue of indicators that can directly or
      indirectly help recognize land degradation features in the visible, infrared, and
      microwave regions of the electromagnetic spectrum are discussed. Factors
      considered when selecting indicators for establishing land degradation baselines
      include, among others, the mapping scale, the spectral characteristics of the
      sensors, and the time of image acquisition. The validation methods used to assess
      the accuracy of maps produced with satellite data are discussed as well.

PMID- 20048294
TI  - Radar remote sensing of wind-driven land degradation processes in northeastern
      Patagonia.
AB  - Wind-driven land degradation negatively impacts on rangeland production and
      infrastructure in the Valdes Peninsula, northeastern Patagonia. The Valdes
      Peninsula has the most noticeable dunefields of the Patagonian drylands. Wind
      erosion has been assessed at different scales in this region, but often with
      limited data. In general, terrain features caused by wind activity are better
      discriminated by active microwaves than by sensors operating in the visible and
      infrared regions of the electromagnetic spectrum. This paper aims to analyze wind
      driven land degradation processes that control the radar backscatter observed in
      different sources of radar imagery. We used subsets derived from SIR-C, ERS-1 and
      2, ENVISAT ASAR, RADARSAT-1, and ALOS PALSAR data. The visibility of aeolian
      features on radar images is mostly a function of wavelength, polarization, and
      incidence angle. Stabilized sand deposits are clearly observed in radar images,
      with defined edges but also signals of ongoing wind erosion. One of the most
      conspicuous features corresponds to old track sand dunes, a mixture of active and
      inactive barchanoid ridges and parabolic dunes. This is a clear example of
      deactivation of migrating dunes under the influence of vegetation. The L-band
      data reveal details of these sand ridges, whereas the C-band data only allow
      detecting a few of the larger tracks. The results of this study enable us to make
      recommendations about the utility of some radar sensor configurations for wind
      driven land degradation reconnaissance in mid-latitude regions.

PMID- 20048295
TI  - A review of vegetated buffers and a meta-analysis of their mitigation efficacy in
      reducing nonpoint source pollution.
AB  - Vegetated buffers are a well-studied and widely used agricultural management
      practice for reducing nonpoint-source pollution. A wealth of literature provides
      experimental data on their mitigation efficacy. This paper aggregated many of
      these results and performed a meta-analysis to quantify the relationships between
      pollutant removal efficacy and buffer width, buffer slope, soil type, and
      vegetation type. Theoretical models for removal efficacy (Y) vs. buffer width (w)
      were derived and tested against data from the surveyed literature using
      statistical analyses. A model of the form Y = K x (1-e(-bxw)), (0 < K < or = 100)
      successfully captured the relationship between buffer width and pollutant
      removal, where K reflects the maximum removal efficacy of the buffer and b
      reflects its probability to remove any single particle of pollutant in a unit
      distance. Buffer width alone explains 37, 60, 44, and 35% of the total variance
      in removal efficacy for sediment, pesticides, N, and P, respectively. Buffer
      slope was linearly associated with sediment removal efficacy either positively
      (when slope < or = 10%) or negatively (when slope > 10%). Buffers composed of
      trees have higher N and P removal efficacy than buffers composed of grasses or
      mixtures of grasses and trees. Soil drainage type did not show a significant
      effect on pollutant removal efficacy. Based on our analysis, a 30-m buffer under
      favorable slope conditions (approximately 10%) removes more than 85% of all the
      studied pollutants. These models predicting optimal buffer width/slope can be
      instrumental in the design, implementation, and modeling of vegetated buffers for
      treating agricultural runoff.

PMID- 20048296
TI  - Lag time in water quality response to best management practices: a review.
AB  - Nonpoint source (NPS) watershed projects often fail to meet expectations for
      water quality improvement because of lag time, the time elapsed between adoption
      of management changes and the detection of measurable improvement in water
      quality in the target water body. Even when management changes are well-designed
      and fully implemented, water quality monitoring efforts may not show definitive
      results if the monitoring period, program design, and sampling frequency are not
      sufficient to address the lag between treatment and response. The main components
      of lag time include the time required for an installed practice to produce an
      effect, the time required for the effect to be delivered to the water resource,
      the time required for the water body to respond to the effect, and the
      effectiveness of the monitoring program to measure the response. The objectives
      of this review are to explore the characteristics of lag time components, to
      present examples of lag times reported from a variety of systems, and to
      recommend ways for managers to cope with the lag between treatment and response.
      Important processes influencing lag time include hydrology, vegetation growth,
      transport rate and path, hydraulic residence time, pollutant sorption properties,
      and ecosystem linkages. The magnitude of lag time is highly site and pollutant
      specific, but may range from months to years for relatively short-lived
      contaminants such as indicator bacteria, years to decades for excessive P levels
      in agricultural soils, and decades or more for sediment accumulated in river
      systems. Groundwater travel time is also an important contributor to lag time and
      may introduce a lag of decades between changes in agricultural practices and
      improvement in water quality. Approaches to deal with the inevitable lag between
      implementation of management practices and water quality response lie in
      appropriately characterizing the watershed, considering lag time in selection,
      siting, and monitoring of management measures, selection of appropriate
      indicators, and designing effective monitoring programs to detect water quality
      response.

PMID- 20048297
TI  - Methane flux in cropland and adjacent riparian buffers with different vegetation
      covers.
AB  - While water quality functions of conservation buffers established adjacent to
      cropped fields have been widely documented, the relative contribution of these re
      established perennial plant systems to greenhouse gases has not been completely
      documented. In the case of methane (CH(4)), these systems have the potential to
      serve as sinks of CH(4) or may provide favorable conditions for CH(4) production.
      This study quantifies CH(4) flux from soils of riparian buffer systems comprised
      of three vegetation types and compares these fluxes with those of adjacent crop
      fields. We measured soil properties and diel and seasonal variations of CH(4)
      flux in 7 to 17 yr-old re-established riparian forest buffers, warm-season and
      cool-season grass filters, and an adjacent crop field located in the Bear Creek
      watershed in central Iowa. Forest buffer and grass filter soils had significantly
      lower bulk density (P < 0.01); and higher pH (P < 0.01), total carbon (TC) (P <
      0.01), and total nitrogen (TN) (P < 0.01) than crop field soils. There was no
      significant relationship between CH(4) flux and soil moisture or soil temperature
      among sites within the range of conditions observed. Cumulative CH(4) flux was 
      0.80 kg CH(4)-C ha(-1) yr(-1) in the cropped field, -0.46 kg CH(4)-C ha(-1) yr(
      1) within the forest buffers, and 0.04 kg CH(4)-C ha(-1) yr(-1) within grass
      filters, but difference among vegetation covers was not significant. Results
      suggest that CH(4) flux was not changed after establishment of perennial
      vegetation on cropped soils, despite significant changes in soil properties.

PMID- 20048298
TI  - Greenhouse gas, animal performance, and bacterial population structure responses
      to dietary monensin fed to dairy cows.
AB  - The present study investigated the effects of a feed additive and rumen microbial
      modifier, monensin sodium (monensin), on selected variables in lactating dairy
      cows. Monensin fed cows (MON, 600 mg d(-1)) were compared with untreated control
      cows (CON, 0 mg d(-1)) with respect to the effects of monensin on the production
      of three greenhouse gases (GHG), methane (CH(4)), nitrous oxide (N(2)O), and
      carbon dioxide (CO(2)), along with animal performance (dry matter intake; DMI),
      milk production, milk components, plasma urea nitrogen (PUN), milk urea nitrogen
      (MUN), and the microbial population structure of fresh feces. Measurements of GHG
      were collected at Days 14 and 60 in an environmental chamber simulating
      commercial dairy freestall housing conditions. Milk production and DMI
      measurements were collected twice daily over the 60-d experimental period; milk
      components, PUN, and MUN were measured on Days 14 and 60. The microbial
      population structure of feces from 6 MON and 6 CON cows was examined on three
      different occasions (Days 14, 30, and 60). Monensin did not affect emissions of
      methane (CH(4)), nitrous oxide (N(2)O), and carbon dioxide (CO(2)). Over a 24-h
      period, emissions of CH(4), N(2)O, and CO(2) decreased in both MON and CON
      groups. Animal performance and the microbial population structure of the animal
      fresh waste were also unaffected for MON vs. CON cows.

PMID- 20048299
TI  - Influence of urea fertilizer placement on nitrous oxide production from a silt
      loam soil.
AB  - Urea placement in band or nests has been shown to enhance N use efficiency, but
      limited work has been done to assess its affect on N(2)O emissions. This study
      compared N(2)O emissions from urea prills applied to an Amsterdam silt loam (fine
      silty, mixed, superactive, frigid Typic Haplustolls) using broadcast, band, and
      nest placements. Experiments were conducted in greenhouse pots (200 kg N ha(-1))
      and in canola (Brassica rapa L.) seeded fields using rates of 100 kg N ha(-1)
      (recommended) and 200 kg N ha(-1). Urea placement affected N(2)O emission
      patterns and cumulative N(2)O losses in the greenhouse and field. Urea prills
      placed in nests, and sometimes bands delayed N(2)O production with peak flux
      activity occurring later, and elevated emission activity being more prolonged
      than for broadcast applications. Differences were more obvious at 200 kg N ha(
      1). These effects were attributed to a delay in urea hydrolysis and inhibition of
      nitrification. The fraction of applied urea-N lost as N(2)O for broadcast, band,
      and nest placements applied at the recommended rate averaged 2.0, 2.7, and 5.8 g
      N kg(-1) N, respectively. The fraction of applied urea-N lost as N(2)O averaged
      2.9, 10.4, and 9.2 g N kg(-1) N for broadcast, band, and nest placements when
      urea-N rate was increased from 100 to 200 kg N ha(-1), respectively. Greater
      N(2)O production with nest placement may in part be due to significant soil NO(2)
      N accumulations. Potential benefits to crop fertilizer use efficiency that come
      with placement of urea in concentrated zones may lead to enhanced N(2)O
      production.

PMID- 20048300
TI  - Simplified method for quantifying theoretical underestimation of chamber-based
      trace gas fluxes.
AB  - Closed chambers used to measure soil-atmosphere exchange of trace gases including
      nitrous oxide (N(2)O) and carbon dioxide (CO(2)) generate errors due to
      suppression of the gas concentration gradient at the soil-atmosphere interface. A
      method is described here for estimating the magnitude of flux underestimation
      arising from chamber deployment. The technique is based on previously established
      gas transport theory and has been simplified to facilitate application while
      preserving the fundamental physical relationships. The method avoids the use of
      nonlinear regression but requires knowledge of soil properties including texture,
      bulk density, water content, temperature, and pH. Two options are presented: a
      numerical technique which is easily adapted to spreadsheet application, and a
      graphical method requiring minimal calculation. In both cases, the magnitude of
      theoretical flux underestimation (TFU) is determined, taking into account effects
      of chamber geometry and deployment time, the flux-calculation scheme, and
      properties of the soil and gas under consideration. Application to actual data
      and recent studies confirmed that TFU can vary widely within and across sites.
      The analysis also revealed a highly linear correlation between soil water content
      and TFU, suggesting that previously observed relationships between water content
      and trace gas flux may in part reflect artifacts of chamber methodology. The
      method described here provides a practical means of improving the absolute
      accuracy of flux estimates and normalizing data obtained using different chamber
      designs in different soils.

PMID- 20048301
TI  - Soil carbon dynamics and carbon budget of newly reconstructed tall-grass prairies
      in south central Iowa.
AB  - In addition to their aesthetic and environmental qualities, reconstructed
      prairies can act as C sinks and potentially offset rising atmospheric CO(2)
      concentration. The objective of this study was to quantify C budget components of
      newly established prairies on previously cultivated land. Net ecosystem
      production (NEP) was estimated using a C budgeting approach that assessed SOC
      content, soil surface CO(2)-C emission, and above- and belowground plant biomass.
      Study was conducted in southern Iowa, in 2005 to 2007. Results show that
      differences between sites for potential total C input were primarily due to root
      biomass contributions, which ranged from 0.8 to 5.4 Mg C ha(-1). Average
      potential aboveground biomass C input was 2.7 Mg C ha(-1) in 2006 and 5.5 Mg C
      ha(-1) in 2007. Total soil CO(2)-C emissions from heterotrophic respiration
      increased as prairie age increased from 2.9 to 4.0 Mg C ha(-1) and 3.1 to 4.7 Mg
      C ha(-1) in 2006 and 2007, respectively. Determination of NEP showed that the
      1998 and 2003 reconstructed prairie sites had the greatest potential for soil C
      sequestration at 4.1 and 4.4 Mg C ha(-1). Increases in SOC content were only
      observed in the youngest established prairie site (2003) and the no-till site in
      2003 at 2.1 and 2.6 Mg C ha(-1) yr(-1), respectively. Declines of SOC
      sequestration rates occurred when potential C equilibrium was reached (R(h) =
      NPP) within 10 yr since prairie establishment.

PMID- 20048302
TI  - Identification of Naegleria fowleri in warm ground water aquifers.
AB  - The free-living amoeba Naegleria fowleri was identified as the etiological agent
      of primary amoebic meningoencephalitis that caused the deaths of two children in
      Peoria, Arizona, in autumn of 2002. It was suspected that the source of N.
      fowleri was the domestic water supply, which originates from ground water
      sources. In this study, ground water from the greater Phoenix Metropolitan area
      was tested for the presence of N. fowleri using a nested polymerase chain
      reaction approach. Phylogenetic analyses of 16S rRNA sequences of bacterial
      populations in the ground water were performed to examine the potential link
      between the presence of N. fowleri and bacterial groups inhabiting water wells.
      The results showed the presence of N. fowleri in five out of six wells sampled
      and in 26.6% of all ground water samples tested. Phylogenetic analyses showed
      that beta- and gamma-proteobacteria were the dominant bacterial populations
      present in the ground water. Bacterial community analyses revealed a very diverse
      community structure in ground water samples testing positive for N. fowleri.

PMID- 20048303
TI  - Trends and transformation of nutrients and pesticides in a coastal plain aquifer
      system, United States.
AB  - Four local-scale sites in areas with similar corn (Zea mays L.) and soybean
      [Glycine max (L.) Merr.] agriculture were studied to determine the effects of
      different hydrogeologic settings of the Northern Atlantic Coastal Plain (NACP) on
      the transport of nutrients and pesticides in groundwater. Settings ranged from
      predominantly well-drained soils overlying thick, sandy surficial aquifers to
      predominantly poorly drained soils with complex aquifer stratigraphy and high
      organic matter content. Apparent age of groundwater, dissolved gases, N isotopes,
      major ions, selected pesticides and degradates, and geochemical environments in
      groundwater were studied. Agricultural chemicals were the source of most
      dissolved ions in groundwater. Specific conductance was strongly correlated with
      reconstructed nitrate (the sum of N in nitrate and N gas) (R(2) = 0.81, p <
      0.0001), and is indicative of the relative degree of agricultural effects on
      groundwater. Trends in nitrate were primarily related to changes in manure and
      fertilizer use at the well-drained sites where aquifer conditions were
      consistently oxic. Nitrate was present in young groundwater but completely
      removed over time through denitrification at the poorly drained sites where there
      were variations in chemical input and in geochemical environment. Median
      concentrations of atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine
      2,4-diamine), metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1
      methylethyl)acetamide), and some of their common degradates were higher at well
      drained sites than at poorly drained sites, with concentrations of degradates
      generally higher than those of the parent compounds at all sites. An increase in
      the percentage of deethylatrazine to total atrazine over time at one well-drained
      site may be related to changes in manure application.

PMID- 20048304
TI  - Use of insoluble polyacrylate polymers to aid phytostabilization of mine soils:
      effects on plant growth and soil characteristics.
AB  - We evaluated the use of polyacrylate polymers to aid phytostabilization of mine
      soils. In a pot experiment, perennial ryegrass was grown in a mine soil and in
      uncontaminated soil. Growth was stimulated in the polymer-amended mine soil
      compared with an unamended control, and water-extractable levels of soil Cu and
      Zn decreased after polymer application. In an experiment performed in six 60-cm
      diameter cylinders filled with fertilized mine soil, polymers were applied to
      three cylinders, with the remainder used as unamended control. Total biomass
      produced by indigenous plant species sown in polymer-amended soil was 1.8 (Spring
      Summer) or 2.4 times (Fall-Winter) greater than that of plants from unamended
      soil. The application of polymers to the mine soil led to the greatest activity
      of soil enzymes. Soil pH, biomass of Spergularia purpurea and Chaetopogon
      fasciculatus, and activities of protease and cellulase had large loadings on
      principal component (PC)1, whereas growth of Briza maxima and the activities of
      urease, acid phosphatase, and beta-glucosidase had large loadings on PC2. The
      treatments corresponding to controls were located on the negative side of PC1 and
      PC2. Amended treatments were on the positive side of PC2 (Spring-Summer) or on
      the positive side of PC1 (Fall-Winter), demonstrating differential responses of
      plants and soil parameters in the two growth cycles.

PMID- 20048305
TI  - Dynamic factor analysis for estimating ground water arsenic trends.
AB  - Drinking ground water containing high arsenic (As) concentrations has been
      associated with blackfoot disease and the occurrence of cancer along the
      southwestern coast of Taiwan. As a result, 28 ground water observation wells were
      installed to monitor the ground water quality in this area. Dynamic factor
      analysis (DFA) is used to identify common trends that represent unexplained
      variability in ground water As concentrations of decommissioned wells and to
      investigate whether explanatory variables (total organic carbon [TOC], As,
      alkalinity, ground water elevation, and rainfall) affect the temporal variation
      in ground water As concentration. The results of the DFA show that rainfall
      dilutes As concentration in areas under aquacultural and agricultural use.
      Different combinations of geochemical variables (As, alkalinity, and TOC) of
      nearby monitoring wells affected the As concentrations of the most decommissioned
      wells. Model performance was acceptable for 11 wells (coefficient of efficiency
      >0.50), which represents 52% (11/21) of the decommissioned wells. Based on DFA
      results, we infer that surface water recharge may be effective for diluting the
      As concentration, especially in the areas that are relatively far from the
      coastline. We demonstrate that DFA can effectively identify the important factors
      and common effects representing unexplained variability common to decommissioned
      wells on As variation in ground water and extrapolate information from existing
      monitoring wells to the nearby decommissioned wells.

PMID- 20048306
TI  - Determining phosphorus and sediment release rates from five Irish tillage soils.
AB  - The aim of this study was to compare the nutrient and sediment releases from five
      Irish tillage soils, inclined at 10- and 15-degree slopes, under a simulated
      rainfall intensity of 30 mm h(-1) in a controlled laboratory study. Using the
      relationship between soil test phosphorus (STP) in the five soils and the
      dissolved reactive phosphorus (DRP) released in surface runoff, a runoff
      dissolved phosphorus risk indicator (RDPRI) was developed to identify the STP
      level for Irish tillage soils above which there may be a potential threat to
      surface water quality. The results of this study indicated that tillage soils may
      produce surface runoff P concentrations in excess of 30 microg L(-1) (the value
      above which eutrophication of rivers is likely to occur and the maximum allowable
      concentration of DRP in rivers under the EU Water Framework Directive, WFD) if
      their Morgan's phosphorus (P(m)), Mehlich 3 phosphorus (M3-P), and water
      extractable phosphorus (WEP) concentrations exceed 9.5 mg L(-1), 67.2 mg kg(-1),
      and 4.4 mg kg(-1), respectively. This work reinforces the statutory agronomic
      based requirements of the European Communities (Good Agricultural Practice for
      Protection of Waters) Regulations 2009 (S.I. no. 101 of 2009). A statistical
      analysis showed that WEP gave the best prediction for runoff DRP.

PMID- 20048307
TI  - Spatially distributed lateral nitrate transport at the catchment scale.
AB  - In river catchments, N transformation and storage processes during lateral
      transport are important in controlling N loads of surface waters. There is a lack
      of approaches which capture lateral flows and associated N transformation in a
      spatially distributed way. The aim of this paper is to develop a new conceptual N
      transport and transformation model which simulates the lateral nitrate transport
      in subsurface flow from the source area to the receiving water body. The
      developed tool is based on the object modeling system (OMS) framework and
      consists of the analytical spatially distributed hydrological model J2000, the
      nitrate recharge model Meta Candy and a new groundwater N routing component.
      Nitrate degradation in groundwater is calculated stoichiometrically according to
      a predefined amount on oxidizable substrate. The new modeling approach was tested
      in a small agricultural lower mountain range catchment of Thuringia, Germany. The
      calibration of the N model using a 4-yr period showed reasonable results for
      nitrate load calculations with a Nash and Sutcliff coefficient of 0.78. The 3-yr
      validation period produced Nash-Sutcliff (NS) values of 0.75. There was a clear
      relationship of the goodness-of-fit between the hydrological simulations and the
      nitrate concentration calculations. Due to short residence times of the interflow
      nitrate degradation was restricted to slow base flow components. The new approach
      can be used to target N source areas within a catchment and assess the impact of
      these source areas on the N load of surface waters in a spatially distributed
      manner.

PMID- 20048308
TI  - Selecting and applying cesium-137 conversion models to estimate soil erosion
      rates in cultivated fields.
AB  - The fallout radionuclide cesium-137 ((137)Cs) has been successfully used in soil
      erosion studies worldwide. However, discrepancies often exist between the erosion
      rates estimated using various conversion models. As a result, there is often
      confusion in the use of the various models and in the interpretation of the data.
      Therefore, the objective of this study was to test the structural and
      parametrical uncertainties associated with four conversion models typically used
      in cultivated agricultural landscapes. For the structural uncertainties, the Soil
      Constituent Redistribution by Erosion Model (SCREM) was developed and used to
      simulate the redistribution of fallout (137)Cs due to tillage and water erosion
      along a simple two-dimensional (horizontal and vertical) transect. The SCREM
      predicted (137)Cs inventories were then imported into the conversion models to
      estimate the erosion rates. The structural uncertainties of the conversion models
      were assessed based on the comparisons between the conversion-model-estimated
      erosion rates and the erosion rates determined or used in the SCREM. For the
      parametrical uncertainties, test runs were conducted by varying the values of the
      parameters used in the model, and the parametrical uncertainties were assessed
      based on the responsive changes of the estimated erosion rates. Our results
      suggest that: (i) the performance/accuracy of the conversion models was largely
      dependent on the relative contributions of water vs. tillage erosion; and (ii)
      the estimated erosion rates were highly sensitive to the input values of the
      reference (137)Cs level, particle size correction factors and tillage depth.
      Guidelines were proposed to aid researchers in selecting and applying the
      conversion models under various situations common to agricultural landscapes.

PMID- 20048309
TI  - A watershed-scale assessment of cost-effectiveness of sediment abatement with
      flow diversion terraces.
AB  - Soil conservation beneficial management practices (BMPs) are effective at
      controlling soil loss from farmlands and minimizing water pollution in
      agricultural watersheds. However, costs associated with implementing and
      maintaining these practices are high and often deter farmers from using them.
      Consequently, it is necessary to conduct cost-benefit analysis of BMP
      implementation to assist decision-makers with planning to provide the greatest
      level of environmental protection with limited resources and funding. The Soil
      and Water Assessment Tool (SWAT) was used to evaluate the efficacy of flow
      diversion terraces (FDT) in abating sediment yield at the outlet of Black Brook
      Watershed (BBW), northwestern New Brunswick. Different FDT-implementation
      scenarios were expressed as the ratio of land area protected by FDT to the total
      cultivated area. From this analysis, we found that average annual sediment yield
      decreased exponentially with increased FDT protection. When the proportion of FDT
      protected areas was low, sediment reductions caused by FDT increased sharply with
      increasing use of FDT. Similarly, marginal sediment yield abatement costs (dollar
      per tonne of sediment reduction) increased exponentially with increasing
      proportion of FDT-protected area. The results indicated that increasing land
      protection with FDT from 6 to 50% would result in a reduction of about 2.1 tonne
      ha(-1) yr(-1) and costs of sediment reduction increased from $7 to $12 per tonne.
      Increasing FDT-protected cropland from 50 to 100%, a reduction of about 0.9 tonne
      of sediment ha(-1) yr(-1) would occur and the costs would increase from $12 to
      $53 per tonne of sediment yield reduction.

PMID- 20048310
TI  - Sorption of sulfonamide antimicrobial agents to humic acid-clay complexes.
AB  - The interaction of sulfonamide antimicrobial agents with smectite clay minerals
      and humic acid (HA)-clay complexes was investigated in batch experiments to
      assess the influence of adsorbed humic acid on sulfonamide sorption. Soil HA-clay
      complexes were produced at HA:clay ratios of 1:5, 1:50, and 1:100 (w/w).
      Vibrational and electronic spectroscopy indicated the preferential adsorption of
      polar and aliphatic components of HA to smectite surfaces, a phenomenon most
      readily discerned at the two lower HA:clay ratios (1:50 and 1:100). Humic acid
      adsorption to smectite clay minerals enhanced sulfamethazine [2-(p
      aminobenzenesulfonamido)-4,6-dimethyl pyrimidine] sorption, especially at the
      highest HA:clay ratio (1:5). Sulfamethazine sorption to adsorbed HA generally
      increased with the abundance of carboxyl (and possibly other O- and N-containing)
      moieties and aliphatic carbon content. Both the smectite surface and the adsorbed
      humic acids contributed to sulfamethazine sorption-desorption hysteresis;
      hysteresis in sulfamethazine sorption to the adsorbed humic acids was equal to or
      larger than for adsorption to the smectites. Competitive sorption with a
      structurally similar sulfonamide antimicrobial was apparent only at high
      competitor concentrations. This study indicates that sorption to organic carbon
      and clay mineral surfaces as well as the hysteretic sorption behavior warrant
      consideration in predicting the transport of these antimicrobial agents in soils
      and subsurface environments.

PMID- 20048311
TI  - Effect of combined Bacillus subtilis on the sorption of phenanthrene and 1,2,3
      trichlorobenzene onto mineral surfaces.
AB  - In the natural environment, minerals are often associated with coexisting
      microorganisms. These interactions have profound impacts on the fate of a wide
      variety of contaminants. However, little information is available on the sorption
      of hydrophobic organic compounds (HOC), such as polycyclic aromatic hydrocarbons
      and chlorinated benzenes, onto the composites of minerals with bacteria, and
      knowledge of the influence of combined bacteria on HOC sorption to minerals is
      limited. In our study, sorption isotherms of phenanthrene (Phen) and 1,2,3
      trichlorobenzene (TCB) onto Bacillus subtilis, minerals (kaolinite,
      montmorillonite, and goethite), and mineral-B. subtilis composites were studied
      to determine the role of B. subtilis in sorption. For pure mineral systems, the
      order of Phen and TCB sorption affinity was montmorillonite > kaolinite >
      goethite. For mineral-B. subtilis composites, the trend was montmorillonite >
      goethite > kaolinite, consistent with that of their ability to combine with
      bacteria. The coating of B. subtilis with minerals enhanced the sorption due to
      the strong sorption of Phen and TCB onto B. subtilis cells and the increase of
      total organic carbon of minerals. With increasing B. subtilis concentration,
      sorption of Phen and TCB on pure B. subtilis cells decreased, but sorption on
      kaolinite surface increased. Sodium azide can greatly reduce sorption capacity
      but increases sorption linearity for B. subtilis and mineral-B. subtilis
      composites. Compared with TCB, Phen had higher sorption affinity due to its high
      hydrophobicity. Our results may be useful for understanding the role of bacteria
      in regulating the distribution and transport of HOCs in the environment.

PMID- 20048312
TI  - Effect of plant age on PCB accumulation by Cucurbita pepo ssp. pepo.
AB  - A greenhouse experiment was conducted to investigate polychlorinated biphenyl
      (PCB) uptake and translocation from soil over time in pumpkin plants (Cucurbita
      pepo ssp. pepo cv. Howden). Plants were grown in weathered soil collected from a
      former industrial site contaminated with Aroclor 1248 (mean [PCB](soil) = 6.5 mg
      kg(-1)). Plants were harvested five times over 42 d and analyzed for total PCB
      concentration in the root and shoot tissues. The concentration of PCBs in the
      root was not significantly different between harvests (mean [PCB](root) = 21.5 mg
      kg(-1)). The concentration of PCBs in the shoots was also relatively stable over
      time (mean [PCB](shoot) = 3.5 mg kg(-1)) despite increases in shoot biomass
      (fresh weight of 4.3 g at Day 12 to 59 g at Day 42). This suggests that PCBs were
      continuously accumulated throughout the growth period. The trends found in this
      study indicate the optimal time to harvest C. pepo ssp pepo plants to maximize
      PCB phytoextraction is when the plant shoot has reached its maximum biomass.

PMID- 20048313
TI  - Responses of a dominant temperate grassland plant (Leymus chinensis) to elevated
      carbon dioxide and nitrogen addition in China.
AB  - The impact of elevated atmospheric CO(2) concentration on plant communities is
      varied and strongly dependent on the dominant species response, as well as
      nutrient conditions. Responses of a dominant species (Leymus chinensis) to
      elevated CO(2) and N application were examined with open-top chambers in a
      typical temperate grassland in northern China for 3 yr. The significant effect of
      elevated CO(2) on L. chinensis growth was mainly reflected in the higher
      photosynthetic rates, increased leaf number, larger shoot and root biomass, and
      higher root/shoot (R/S) ratio. Enhancement of root biomass induced by elevated
      CO(2) was larger (40%) than that of shoot biomass (9%). In contrast, N
      application had a significant impact on most growth indices examined in this
      study, which was reflected in the enhanced aboveground growth and depressed
      belowground growth. Nitrogen application significantly reduced the R/S ratio by
      an average of 40%. Nitrogen addition significantly enhanced the proportion of
      senescent biomass and decreased the proportion of green leaf biomass under
      elevated CO(2). There were no CO(2) x N interactions on most of the measured
      variables, except on photosynthetic rate and the proportion of aboveground
      biomass. Plant growth variables showed high interannual variation. These results
      indicate that belowground growth of L. chinensis is more sensitive to elevated
      CO(2) than is the aboveground. Aboveground growth of L. chinensis is much more
      sensitive to N application than to CO(2) enrichment. Therefore, the effect of
      elevated CO(2) on L. chinensis steppe is more likely to be underestimated if only
      aboveground parts are considered.

PMID- 20048314
TI  - Combining LiDAR and IKONOS data for eco-hydrological classification of an
      ombrotrophic peatland.
AB  - Remote sensing techniques have potential for peatland monitoring, but most
      previous work has focused on spectral approaches that often result in poor
      discrimination of cover types and neglect structural information. Peatlands
      contain structural "microtopes" (e.g., hummocks and hollows) which are linked to
      hydrology, biodiversity and carbon sequestration, and information on surface
      structure is thus a useful proxy for peatland condition. The objective of this
      work was to develop and test a new eco-hydrological mapping technique for
      ombrotrophic (rain-fed) peatlands using a combined spectral-structural remote
      sensing approach. The study site was Wedholme Flow, Cumbria, UK. Airborne light
      dectection and ranging (LiDAR) data were used with IKONOS data in a combined
      multispectral-structural approach for mapping peatland condition classes. LiDAR
      data were preprocessed so that spatial estimates of minimum and maximum land
      surface height, variance and semi-variance (from semi-variogram analysis) were
      extracted. These were assimilated alongside IKONOS data into a maximum likelihood
      classification procedure, and thematic outputs were compared. Ecological survey
      data were used to validate the results. Considerable improvements in thematic
      separation of peatland classes were achieved when spatially-distributed
      measurements of LiDAR variance or semi-variance were included. Specifically, the
      classification accuracy improved from 71.8% (IKONOS data only) to 88.0% when a
      LiDAR semi-variance product was used. Of note was the improved delineation of
      management classes (including Eriophorum bog, active raised bog and degraded
      raised bog). The application of a combined textural-optical approach can improve
      land cover mapping in areas where reliance on purely spectral discrimination
      approaches would otherwise result in considerable thematic uncertainty.

PMID- 20048315
TI  - Denitrification of nitrogen released from senescing algal biomass in coastal
      agricultural headwater streams.
AB  - Assimilation of inorganic N by photoautotrophs has positive impacts on nutrient
      retention; however this retention is only temporary. As the biomass senesces,
      organic and inorganic forms of N are released back to the stream where they can
      be further transformed (i.e., nitrification, denitrification) or exported
      downstream. The purpose of this study was to assess the fate of the remineralized
      N, particularly the potential for removal by denitrification. Experiments were
      conducted on intact sediment cores from streams in an agricultural watershed.
      Cores were amended with varying ages of algal leachate and denitrification rates
      were measured with a membrane inlet mass spectrometer. Results of this study
      demonstrated that senescing algal biomass stimulated denitrification rates and
      provided a source of N and labile C to denitrifiers. Regardless of leachate age,
      addition of leachate to intact cores revealed a net loss of dissolved inorganic N
      from the water column. Denitrification rates were most strongly related to
      concentrations of dissolved and particulate C in the overlying water and
      secondarily to C quality (molar C to N ratio of total dissolved C and N) and
      NO(3)(-) flux. Using a mass balance approach, the proportion of N from senescing
      algal biomass that was denitrified accounted for as much as 10% of the total
      dissolved nitrogen (TDN) and up to 100% of the NO(3)(-) during a 3-h experiment.
      These results suggest an important link between instream algal uptake and
      eventual denitrification thereby providing a pathway for permanent removal of
      watershed-derived N from the stream ecosystem.

PMID- 20048316
TI  - Phosphorus runoff from turfgrass as affected by phosphorus fertilization and
      clipping management.
AB  - Phosphorus enrichment of surface water is a concern in many urban watersheds. A 3
      yr study on a silt loam soil with 5% slope and high soil test P (27 mg kg(-1)
      Bray P1) was conducted to evaluate P fertilization and clipping management
      effects on P runoff from turfgrass (Poa pratensis L.) under frozen and nonfrozen
      conditions. Four fertilizer treatments were compared: (i) no fertilizer, (ii)
      nitrogen (N)+potassium (K)+0xP, (iii) N+K+1xP, and (iv) N+K+3xP. Phosphorus rates
      were 21.3 and 63.9 kg ha(-1) yr(-1) the first year and 7.1 and 21.3 kg ha(-1) yr(
      1) the following 2 yr. Each fertilizer treatment was evaluated with clippings
      removed or clippings recycled back to the turf. In the first year, P runoff
      increased with increasing P rate and P losses were greater in runoff from frozen
      than nonfrozen soil. In year 2, total P runoff from the no fertilizer treatment
      was greater than from treatments receiving fertilizer. This was because reduced
      turf quality resulted in greater runoff depth from the no fertilizer treatment.
      In year 3, total P runoff from frozen soil and cumulative total P runoff
      increased with increasing P rate. Clipping management was not an important factor
      in any year, indicating that returning clippings does not significantly increase
      P runoff from turf. In the presence of N and K, P fertilization did not improve
      turf growth or quality in any year. Phosphorus runoff can be reduced by not
      applying P to high testing soils and avoiding fall applications when P is needed.

PMID- 20048317
TI  - Impacts of fertilization on water quality of a drained pine plantation: a worst
      case scenario.
AB  - Intensive plantation forestry will be increasingly important in the next 50 yr to
      meet the high demand for domestic wood in the United States. However, forest
      management practices can substantially influence downstream water quality and
      ecology. This study analyses, the effect of fertilization on effluent water
      quality of a low gradient drained coastal pine plantation in Carteret County,
      North Carolina using a paired watershed approach. The plantation consists of
      three watersheds, two mature (31-yr) and one young (8-yr) (age at treatment). One
      of the mature watersheds was commercially thinned in 2002. The mature unthinned
      watershed was designated as the control. The young and mature-thinned watersheds
      were fertilized at different rates with Arborite (Encee Chemical Sales, Inc.,
      Bridgeton, NC), and boron. The outflow rates and nutrient concentrations in water
      drained from each of the watersheds were measured. Nutrient concentrations and
      loadings were analyzed using general linear models (GLM). Three large storm
      events occurred within 47 d of fertilization, which provided a worst case
      scenario for nutrient export from these watersheds to the receiving surface
      waters. Results showed that average nutrient concentrations soon after
      fertilization were significantly (alpha = 0.05) higher on both treatment
      watersheds than during any other period during the study. This increase in
      nutrient export was short lived and nutrient concentrations and loadings were
      back to prefertilization levels as soon as 3 mo after fertilization.
      Additionally, the mature-thinned watershed presented higher average nutrient
      concentrations and loadings when compared to the young watershed, which received
      a reduced fertilizer rate than the mature-thinned watershed.

PMID- 20048318
TI  - Seasonal losses of dissolved organic carbon and total dissolved solids from rice
      production systems in northern California.
AB  - Water quality concerns have arisen related to rice (Oryza sativa L.) field drain
      water, which has the potential to contribute large amounts of dissolved organic
      carbon (DOC) and total dissolved solids (TDS) to the Sacramento River. Field
      scale losses of DOC or TDS have yet to be quantified. The objectives of this
      study were to evaluate the seasonal concentrations of DOC and TDS in rice field
      drain water and irrigation canals, quantify seasonal fluxes and flow-weighted
      (FW) concentrations of DOC and TDS, and determine the main drivers of DOC and TDS
      fluxes. Two rice fields with different straw management practices (incorporation
      vs. burning) were monitored at each of four locations in the Sacramento Valley.
      Fluxes of DOC ranged from 3.7 to 34.6 kg ha(-1) during the growing season (GS)
      and from 0 to 202 kg ha(-1) during the winter season (WS). Straw management had a
      significant interaction effect with season, as the greatest DOC concentrations
      were observed during winter flooding of straw incorporated fields. Fluxes and
      concentrations of TDS were not significantly affected by either straw management
      or season. Total seasonal water flux accounted for 90 and 88% of the variability
      in DOC flux during the GS and WS, respectively. Peak DOC concentrations occurred
      at the onset of drainflow; therefore, changes in irrigation management may reduce
      peak DOC concentrations and thereby DOC losses. However, the timing of peak DOC
      concentrations from rice fields suggest that rice field drainage water is not the
      cause of peak DOC concentrations in the Sacramento River.

PMID- 20048319
TI  - Phosphorus runoff from waste water treatment biosolids and poultry litter applied
      to agricultural soils.
AB  - Differences in the properties of organic phosphorus (P) sources, particularly
      those that undergo treatment to reduce soluble P, can affect soil P solubility
      and P transport in surface runoff. This 2-yr field study investigated soil P
      solubility and runoff P losses from two agricultural soils in the Mid-Atlantic
      region after land application of biosolids derived from different waste water
      treatment processes and poultry litter. Phosphorus speciation in the biosolids
      and poultry litter differed due to treatment processes and significantly altered
      soil P solubility and dissolved reactive P (DRP) and bioavailable P (FeO-P)
      concentrations in surface runoff. Runoff total P (TP) concentrations were closely
      related to sediment transport. Initial runoff DRP and FeO-P concentrations varied
      among the different biosolids and poultry litter applied. Over time, as sediment
      transport declined and DRP concentrations became an increasingly important
      component of runoff FeO-P and TP, total runoff P was more strongly influenced by
      the type of biosolids applied. Throughout the study, application of lime
      stabilized biosolids and poultry litter increased concentrations of soil-soluble
      P, readily desorbable P, and soil P saturation, resulting in increased DRP and
      FeO-P concentrations in runoff. Land application of biosolids generated from
      waste water treatment processes that used amendments to reduce P solubility
      (e.g., FeCl(3)) did not increase soil P saturation and reduced the potential for
      DRP and FeO-P transport in surface runoff. These results illustrate the
      importance of waste water treatment plant process and determination of specific P
      source coefficients to account for differential P availability among organic P
      sources.

PMID- 20048321
TI  - The green alga, Cladophora, promotes Escherichia coli growth and contamination of
      recreational waters in Lake Michigan.
AB  - A linkage between Cladophora mats and exceedances of recreational water quality
      criteria has been suggested, but not directly studied. This study investigates
      the spatial and temporal association between Escherichia coli concentrations
      within and near Cladophora mats at two northwestern Lake Michigan beaches in Door
      County, Wisconsin. Escherichia coli concentrations in water underlying mats were
      significantly greater than surrounding water (p < 0.001). Below mat E. coli
      increased as the stranded mats persisted at the beach swash zone. Water adjacent
      to Cladophora mats had lower E. coli concentrations, but surpassed EPA swimming
      criteria the majority of sampling days. A significant positive association was
      found between E. coli concentrations attached to Cladophora and in underlying
      water (p < 0.001). The attached E. coli likely acted as a reservoir for
      populating water underlying the mat. Fecal bacterial pathogens, however, could
      not be detected by microbiological culture methods either attached to mat biomass
      or in underlying water. Removal of Cladophora mats from beach areas may improve
      aesthetic and microbial water quality at affected beaches. These associations and
      potential natural growth of E. coli in bathing waters call into question the
      efficacy of using E. coli as a recreational water quality indicator of fecal
      contaminations.

PMID- 20048320
TI  - Modifying broiler diets with phytase and vitamin D metabolite (25-OH D(3)):
      impact on phosphorus in litter, amended soils, and runoff.
AB  - Adding phytase and 25- hydroxycholecalciferol (25-OH D(3)) to broiler diets has
      been shown effective at reducing total P concentrations in broiler litter. This
      study was conducted to determine the impact of field application of broiler
      litter from modified diets on P solubility in litter-amended soils and P losses
      in runoff. Five broiler diets and their resulting litters were evaluated: a high
      P diet, a low P diet, each of those basal diets with phytase added, and a low P
      diet with phytase and 25-OH D(3) added. A field study was initiated at two sites
      with each of the five broiler litters and a commercial P fertilizer (triple
      superphosphate [TSP]) applied at the same total P rate (150 kg P ha(-1)) and a
      control where no P was applied. Soil P was monitored over time at two depths (0-5
      cm and 0-15 cm) soils were collected in the spring and fall to perform rainfall
      simulation studies. Broiler litter or TSP application increased soil water
      soluble P and Mehlich 3-P concentrations relative to the control, however there
      were no consistent differences detected between litter treatments. Results from
      the rainfall simulation experiments indicate that diet modification with phytase
      or 25-OH D(3) does not increase the potential for P losses in runoff from amended
      soils relative to traditional diets. Moreover, broiler diet modification to
      reduce excreted P could be a potentially effective method for reducing watershed
      scale P surpluses in areas of intensive broiler production, without raising
      concerns over soluble P losses from litter-amended soils.

PMID- 20048322
TI  - Transport and fate of phosphorus during and after manure spill simulations.
AB  - Animal manure spills contribute to P loading of surface waters and little is
      known about the effectiveness of the current manure spill clean-up methods to
      mitigate P contamination. Manure spill clean-up consists of containing, removing,
      and land applying the contaminated water column, while P-enriched fluvial
      sediments remain in place. Therefore, the objectives of this study were to (i)
      understand how P partitions between the water column and fluvial sediments during
      a manure spill, and (ii) evaluate the efficacy of current manure spill clean-up
      methods to remediate manure contaminated sediments. Manure spill simulations were
      conducted using fluvarium techniques and sediments collected from three drainage
      areas of two drainage ditches. Sediments with the greatest clay content (33%)
      resulted in a significantly greater P buffering capacity (10.3 L kg(-1)) and
      removed P from the water column at the greatest rate during the manure spill
      simulation relative to sediments with < 6% clay. Phosphorus uptake length for all
      sediments ranged from 574 to 815 m and the adsorption flux ranged from 8.9 to
      16.7 mg m(-2) h(-1). After simulating the current manure spill remediation
      methods, P desorbed to the water from all sediments exceeded the Environmental
      Protection Agency total P criteria (0.076 mg L(-1)) for the region by at least
      67%. Furthermore, results from this study suggest that the current manure spill
      remediation method needs refining to mitigate P from the total fluvial system
      water column and sediment following a spill.

PMID- 20048323
TI  - Simulating pesticide transport from a sloped tropical soil to an adjacent stream.
AB  - Preferential flow from stream banks is an important component of pesticide
      transport in the mountainous areas of northern Thailand. Models can help evaluate
      and interpret field data and help identify the most important transport
      processes. We developed a simple model to simulate the loss of pesticides from a
      sloped litchi (Litchi chinensis Sonn.) orchard to an adjacent stream. The water
      regime was modeled with a two-domain reservoir model, which accounts for rapid
      preferential flow simultaneously with slow flow processes in the soil matrix.
      Preferential flow is triggered when the topsoil matrix is saturated or the
      infiltration capacity exceeded. In addition, close to matrix saturation, rainfall
      events induce water release to the fractures and lead to desorption of pesticides
      from fracture walls and outflow to the stream. Pesticides undergo first order
      degradation and equilibrium sorption to soil matrix and fracture walls. The model
      was able to reproduce the dynamics of the discharge reasonably well (model
      efficiency [EF] = 0.56). The cumulative pesticide mass (EF = 0.91) and the
      pesticide concentration in the stream were slightly underestimated, but the
      deviation from measurement data is acceptable. Shape and timing of the simulated
      concentration peaks occurred in the same pattern as observed data. While the
      effect of surface runoff and preferential interflow on pesticide mass transport
      could not be absolutely clarified, according to our simulations, most
      concentration peaks in the stream are caused by preferential interflow pointing
      to the important role of this flow path in the hilly areas of northern Thailand.

PMID- 20048324
TI  - Leaching of three sulfonylurea herbicides during sprinkler irrigation.
AB  - Sulfonylurea herbicides are widely applied on the Canadian prairies to control
      weeds in a variety of crops. Several sulfonylurea herbicides are mobile in soil,
      and there is concern about their possible movement to ground water. This study
      was performed to assess the susceptibility of three sulfonylurea herbicides
      commonly used in prairie crop production to leach under a worst-case scenario.
      Thifensulfuron-methyl, tribenuron-methyl, and rimsulfuron were applied to a 9-ha
      tile-drained field, and then approximately 300 mm of irrigation water were
      applied over a 2-wk period using a center pivot. The commencement of tile-drain
      flow corresponded to the rise of the water table above tile-drain depth, and peak
      flow rates corresponded to the greatest depths of ground water above the tile
      drains. The volume of irrigation water intercepted by the tile drains in each
      quadrant was determined by site hydrology and represented <10% of the irrigation
      water applied. Concentrations of thifensulfuron-methyl, tribenuron-methyl, and
      rimsulfuron in the tile-drain effluent ranged (analysis by liquid
      chromatography/tandem mass spectrometry) from 2.0 to 248 ng L(-1), not detected
      (nd) to 55 ng L(-1), and nd to 497 ng L(-1), respectively. Total herbicide
      transport from the root zone in each quadrant was estimated at <0.5% of the
      amount of each sulfonylurea herbicide applied. Thifensulfuron-methyl was the only
      herbicide detected in ground water, with concentrations ranging from 1.2 to 2.5
      ng L(-1). With the frequency and amount of rainfall typically encountered in the
      prairie region of Canada, detectable concentrations (>1 ng L(-1)) of these
      sulfonylurea herbicides in ground water would be unlikely.

PMID- 20048325
TI  - Effect of compost-, sand-, or gypsum-amended waste foundry sands on turfgrass
      yield and nutrient content.
AB  - To prevent the 7 to 11 million metric tons of waste foundry sand (WFS) produced
      annually in the USA from entering landfills, current research is focused on the
      reuse of WFSs as soil amendments. The effects of different WFS-containing
      amendments on turfgrass growth and nutrient content were tested by planting
      perennial ryegrass (Lolium perenne L.) and tall fescue (Schedonorus phoenix
      (Scop.) Holub) in different blends containing WFS. Blends of WFS were created
      with compost or acid-washed sand (AWS) at varying percent by volume with WFS or
      by amendment with gypsum (9.6 g gypsum kg(-1) WFS). Measurements of soil
      strength, shoot and root dry weight, plant surface coverage, and micronutrients
      (Al, Fe, Mn, Cu, Zn, B, Na) and macronutrients (N, P, K, S, Ca, Mg) were
      performed for each blend and compared with pure WFS and with a commercial potting
      media control. Results showed that strength was not a factor for any of the
      parameters studied, but the K/Na base saturation ratio of WFS:compost mixes was
      highly correlated with total shoot dry weight for perennial ryegrass (r = 0.995)
      and tall fescue (r = 0.94). This was further substantiated because total shoot
      dry weight was also correlated with shoot K/Na concentration of perennial
      ryegrass (r = 0.99) and tall fescue (r = 0.95). A compost blend containing 40%
      WFS was determined to be the optimal amendment for the reuse of WFS because it
      incorporated the greatest possible amount of WFS without major reduction in
      turfgrass growth.

PMID- 20048326
TI  - Matrix-based fertilizers reduce nutrient and bacterial leaching after manure
      application in a greenhouse column study.
AB  - We tested the efficacy of matrix-based fertilizers (MBFs) to reduce Escherichia
      coli and Enterococcus spp., NH(4), NO(3), dissolved reactive phosphorus (DRP),
      and total phosphorus (TP) in leachate and soil after dairy manure application in
      greenhouse column studies. The MBFs are composed of inorganic N and P in
      compounds that are relatively loosely bound (MBF8) to more tightly bound (MBF9)
      mixtures using combinations of starch, cellulose, lignin, Al(2)(SO(4))(3)18H(2)O,
      and/or Fe(2)(SO(4))(3)3H(2)O to create a matrix that slowly releases the
      nutrients. One day after the first dairy manure application, E. coli numbers were
      greater in leachate from control columns than in leachate from columns receiving
      MBFs. After three dairy manure applications, E. coli and Enterococcus spp.
      numbers in leachates were not consistently different between controls and columns
      receiving MBFs. When MBF8 was applied to the soil, the total amount of DRP, TP,
      NH(4), and NO(3) in leachate was lower than in the control columns. Bermudagrass
      receiving MBFs had greater shoot, root, and total biomass than grass growing in
      the control columns. Grass shoot, root, and total biomass did not differ among
      columns receiving MBFs. Nitrogen and phosphorus bound to the
      Al(2)(SO(4))(3)18H(2)O or Fe(2)(SO(4))(3)3H(2)O-lignin-cellulose matrix become
      gradually available to plants over the growing season. The MBF8 and MBF9
      formulations do not depend on organic or inorganic coatings to reduce N and P
      leaching and have the potential with further testing and development to provide
      an effective method to reduce N and P leaching from soils treated with animal
      waste.

PMID- 20048327
TI  - Phosphorus distribution in untreated and composted solid fractions from slurry
      separation.
AB  - The distribution of phosphorus (P) (water-soluble inorganic P [P(i)], acid
      soluble P(i), and residual P) was determined in 40 samples of solids from solid
      liquid separated slurry. These were collected from separation plants using
      different technologies, separating by simple mechanical means, by flocculation as
      pre-treatment before mechanical separation or by anaerobic digestion followed by
      separation and centrifugation. Simple mechanical separation yielded a low solid
      TP content (8-9 g P kg(-1) dry matter [DM]) compared with separation by
      flocculation (26 g P kg(-1) DM) or by anaerobic digestion-centrifugation (33.4 g
      P kg(-1) DM). Acid-soluble P(i) predominated in the high P-yielding solids,
      whereas organic-bound or residual P was a minor component in all slurry solids.
      Acid-soluble P(i) and residual P were significantly correlated with total
      phosphorus (TP) content (R(2) = 0.855 and R(2) = 0.584), but water-soluble P(i)
      was uncorrelated (R(2) = 0.077). The relative distribution of P(i) to TP in the
      solids showed a high proportion of water-soluble P(i) in solids from simple
      mechanical separation, whereas the absolute concentrations were highest in solids
      from separation by flocculation and anaerobic digestion-centrifugation. Three
      solid fractions, representing the range of solids variability produced by the
      separation techniques, were composted for 30 d, and the P distribution was
      compared before and after composting. Total mass of P was conserved during
      composting, but water-soluble P(i) as a proportion of TP decreased in most cases.
      The most pronounced decrease in water-soluble P(i) was observed during composting
      of the solids separated using flocculation. However, changes in short- to medium
      term bioavailability of P were modest, and thus the potential benefits of
      composting regarding storage and handling can presumably be realized without
      seriously compromising the P fertilization quality.

PMID- 20048328
TI  - Long-term effects of land application of class B biosolids on the soil microbial
      populations, pathogens, and activity.
AB  - This study evaluated the influence of 20 annual land applications of Class B
      biosolids on the soil microbial community. The potential benefits and hazards of
      land application were evaluated by analysis of surface soil samples collected
      following the 20th land application of biosolids. The study was initiated in 1986
      at the University of Arizona Marana Agricultural Center, 21 miles north of
      Tucson, AZ. The final application of biosolids was in March 2005, followed by
      growth of cotton (Gossypium hirsutum L.) from April through November 2005.
      Surface soil samples (0-30 cm) were collected monthly from March 2005, 2 wk after
      the final biosolids application, through December 2005, and analyzed for soil
      microbial numbers. December samples were analyzed for additional soil microbial
      properties. Data show that land application of Class B biosolids had no
      significant long-term effect on indigenous soil microbial numbers including
      bacteria, actinomycetes, and fungi compared to unamended control plots.
      Importantly, no bacterial or viral pathogens were detected in soil samples
      collected from biosolid amended plots in December (10 mo after the last land
      application) demonstrating that pathogens introduced via Class B biosolids only
      survived in soil transiently. However, plots that received biosolids had
      significantly higher microbial activity or potential for microbial
      transformations, including nitrification, sulfur oxidation, and dehydrogenase
      activity, than control plots and plots receiving inorganic fertilizers. Overall,
      the 20 annual land applications showed no long-term adverse effects, and
      therefore, this study documents that land application of biosolids at this
      particular site was sustainable throughout the 20-yr period, with respect to soil
      microbial properties.

PMID- 20048329
TI  - Nitrogen source tracking with delta(15)N content of coastal wetland plants in
      Hawaii.
AB  - Inter- and intra-site comparisons of the nitrogen (N) stable isotope composition
      of wetland plant species have been used to identify sources of N in coastal
      areas. In this study, we compared delta(15)N values from different herbaceous
      wetland plants across 34 different coastal wetlands from the five main Hawaiian
      Islands and investigated relationships of delta(15)N with land use, human
      population density, and surface water quality parameters (i.e., nitrate,
      ammonium, and total dissolved N). The highest delta(15)N values were observed in
      plants from wetlands on the islands of Oahu (8.7-14.6 per thousand) and Maui (8.9
      9.2 per thousand), whereas plants from wetlands on the islands of Kauai, Hawaii,
      and Molokai had delta(15)N values usually <4 per thousand. The enrichment in
      delta(15)N values in plant tissues from wetlands on Oahu and Maui was most likely
      a result of the more developed and densely populated watersheds on these two
      islands. Urban development within a 1000-m radius and population density were
      positively correlated to average delta(15)N vegetation values from each wetland
      site (r = 0.56 and 0.51, respectively; p < 0.001). This suggested that site mean
      delta(15)N values from mixed stands of wetland plants have potential as indices
      of N sources in coastal lowland wetlands in Hawaii and that certain sites on Oahu
      and Maui have experienced significant anthropogenic N loading. This information
      can be used to monitor future changes in N inputs to coastal wetlands throughout
      Hawaii and the Pacific.

PMID- 20048330
TI  - Seeps regulate stream nitrate concentration in a forested Appalachian catchment.
AB  - Surface seeps can be defined as locations where upwelling ground water saturates
      the surface for most of the year and excess ground water can be delivered to the
      stream channel via surface flowpaths. If a stream is predominantly fed by seeps,
      then ground water added to the stream via these surface flowpaths may result in
      reduced interactions with the subsurface riparian zone. It is generally believed
      that seep ground water that upwells and then flows along surface flowpaths can be
      subject to diminished denitrification and biologic uptake processes. Seep effects
      on stream nitrate (NO(3)) concentration were studied in Baldwin Creek (5.35
      km(2)), southwestern Pennsylvania. Nitrate retention within seep zones was
      evaluated over a 1-yr period (May 2002-2003) using a monthly, nested (top and
      bottom of seep) sampling approach along 15 individual seeps. Seep samples were
      analyzed for NO(3)-N, NH(3)-N, and dissolved organic carbon, along with stream
      waters and streamflow measurements at seven stream stations. Seeps were generally
      NO(3) sinks with concentrations decreasing downseep: 31% median annual reduction
      and 73% maximum monthly reduction. During cold and wet periods, seeps frequently
      behaved as NO(3) sources to the stream (NO(3) concentrations increased or
      remained constant downseep). Seep temperature and discharge were related to
      seasonal variability in seep NO(3) retention. Seasonal variations in stream NO(3)
      concentration have been attributed to upland soil and vegetation processes in
      numerous watersheds. At Baldwin Creek, seep NO(3) processing regulated the
      seasonal variability of stream NO(3) concentrations. These results suggest that
      seeps provide important water quality functions and can modulate the effects of
      elevated regional N deposition in Appalachian catchments.

PMID- 20048331
TI  - A method to construct dose-response curves for a wide range of environmental
      factors and plant traits by means of a meta-analysis of phenotypic data.
AB  - In the past, biologists have characterized the responses of a wide range of plant
      species to their environment. As a result, phenotypic data from hundreds of
      experiments are publicly available now. Unfortunately, this information is not
      structured in a way that enables quantitative and comparative analyses. We aim to
      fill this gap by building a large database which currently contains data on 1000
      experiments and 800 species. This paper presents methodology to generalize across
      different experiments and species, taking the response of specific leaf area
      (SLA; leaf area:leaf mass ratio) to irradiance as an example. We show how to
      construct and quantify a normalized mean light-response curve, and subsequently
      test whether there are systematic differences in the form of the curve between
      contrasting subgroups of species. This meta-analysis is then extended to a range
      of other environmental factors important for plant growth as well as other
      phenotypic traits, using >5300 mean values. The present approach, which we refer
      to as 'meta-phenomics', represents a valuable tool in understanding the
      integrated response of plants to their environment and could serve as a benchmark
      for future phenotyping efforts as well as for modelling global change effects on
      both wild species and crops.

PMID- 20048332
TI  - Proteomics of Thlaspi caerulescens accessions and an inter-accession cross
      segregating for zinc accumulation.
AB  - Metal hyperaccumulator plants have previously been characterized by
      transcriptomics, but reports on other profiling techniques are scarce. Protein
      profiles of Thlaspi caerulescens accessions La Calamine (LC) and Lellingen (LE)
      and lines derived from an LCxLE cross were examined here to determine the co
      segregation of protein expression with the level of zinc (Zn) hyperaccumulation.
      Although hydrophobic proteins such as membrane transporters are not disclosed,
      this approach has the potential to reveal other proteins important for the Zn
      hyperaccumulation trait. Plants were exposed to metals. Proteins were separated
      using two-dimensional electrophoresis and those showing differences among
      accessions, lines or metal exposures were subjected to mass-spectrometric
      analysis for identification. Crossing decreased the number of different proteins
      in the lines compared with the parents, more so in the shoots than in the roots,
      but the frequencies of Zn-responsive proteins were about the same in the
      accessions and the selection lines. This supports the finding that the Zn
      accumulation traits are mainly determined by the root and that Zn accumulation
      itself is not the reason for the co-segregation. This study demonstrates that
      crossing accessions with contrasting Zn accumulation traits is a potent tool to
      investigate the mechanisms behind metal hyperaccumulation. Four tentatively
      identified root proteins showed co-segregation with high or low Zn accumulation:
      manganese superoxide dismutase, glutathione S-transferase, S-formyl glutathione
      hydrolase, and translation elongation factor 5A-2. However, these proteins may
      not be the direct determinants of Zn accumulation. The role of these and other
      tentatively identified proteins in Zn accumulation and tolerance is discussed.

PMID- 20048334
TI  - The telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor
      initiating cells leading to decreased proliferation and tumor growth.
AB  - PURPOSE: Telomerase activity is one of the hallmarks of cancer and is a highly
      relevant therapeutic target. The effects of a novel human telomerase antagonist,
      imetelstat, on primary human glioblastoma (GBM) tumor-initiating cells were
      investigated in vitro and in vivo. EXPERIMENTAL DESIGN: Tumor-initiating cells
      were isolated from primary GBM tumors and expanded as neurospheres in vitro. The
      GBM tumor-initiating cells were treated with imetelstat and examined for the
      effects on telomerase activity levels, telomere length, proliferation,
      clonogenicity, and differentiation. Subsequently, mouse orthotopic and
      subcutaneous xenografts were used to assess the in vivo efficacy of imetelstat.
      RESULTS: Imetelstat treatment produced a dose-dependent inhibition of telomerase
      (IC(50) 0.45 micromol/L). Long-term imetelstat treatment led to progressive
      telomere shortening, reduced rates of proliferation, and eventually cell death in
      GBM tumor-initiating cells. Imetelstat in combination with radiation and
      temozolomide had a dramatic effect on cell survival and activated the DNA damage
      response pathway. Imetelstat is able to cross the blood-brain barrier in
      orthotopic GBM xenograft tumors. Fluorescently labeled GBM tumor cells isolated
      from orthotopic tumors, following systemic administration of imetelstat (30 mg/kg
      every day for three days), showed approximately 70% inhibition of telomerase
      activity. Chronic systemic treatment produced a marked decrease in the rate of
      xenograft subcutaneous tumor growth. CONCLUSION: This preclinical study supports
      the feasibility of testing imetelstat in the treatment of GBM patients, alone or
      in combination with standard therapies.

PMID- 20048336
TI  - Actin and cellular architecture at a glance.

PMID- 20048335
TI  - K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia
      patients with residual disease on imatinib mesylate.
AB  - PURPOSE: Chronic myeloid leukemia (CML) can be responsive to T-cell-mediated
      immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM
      CSF producing vaccine derived from a CML cell line that expresses several CML
      associated antigens. A pilot study was developed to determine if K562/GM-CSF
      immunotherapy could improve clinical responses to imatinib mesylate (IM) in
      patients with chronic myeloid leukemia. EXPERIMENTAL DESIGN: Patients with
      chronic phase CML who achieved at least a major cytogeneic response but remained
      with persistent, measurable disease despite one or more years on imatinib
      mesylate were eligible. Each was given a series of four vaccines administered in
      three-week intervals, with or without topical imiquimod, while remaining on a
      stable dose of imatinib mesylate. CML disease burden was measured serially before
      and after vaccination. RESULTS: Nineteen patients were vaccinated, with a median
      duration of previous imatinib mesylate therapy of 37 (13-53) months. Mean PCR
      measurements of BCR-ABL for the group declined significantly following the
      vaccines (P = 0.03). Thirteen patients had a progressive decline in disease
      burden, 8 of whom had increasing disease burden before vaccination. Twelve
      patients achieved their lowest tumor burden measurements to date following
      vaccine, including seven subjects who became PCR-undetectable. CONCLUSIONS:
      K562/GM-CSF vaccine appears to improve molecular responses in patients on
      imatinib mesylate, including achieving complete molecular remissions, despite
      long durations of previous imatinib mesylate therapy.

PMID- 20048337
TI  - Understanding large multiprotein complexes: applying a multiple allosteric
      networks model to explain the function of the Mediator transcription complex.
AB  - The regulation of transcription and of many other cellular processes involves
      large multi-subunit protein complexes. In the context of transcription, it is
      known that these complexes serve as regulatory platforms that connect activator
      DNA-binding proteins to a target promoter. However, there is still a lack of
      understanding regarding the function of these complexes. Why do multi-subunit
      complexes exist? What is the molecular basis of the function of their constituent
      subunits, and how are these subunits organized within a complex? What is the
      reason for physical connections between certain subunits and not others? In this
      article, I address these issues through a model of network allostery and its
      application to the eukaryotic RNA polymerase II Mediator transcription complex.
      The multiple allosteric networks model (MANM) suggests that protein complexes
      such as Mediator exist not only as physical but also as functional networks of
      interconnected proteins through which information is transferred from subunit to
      subunit by the propagation of an allosteric state known as conformational spread.
      Additionally, there are multiple distinct sub-networks within the Mediator
      complex that can be defined by their connections to different subunits; these sub
      networks have discrete functions that are activated when specific subunits
      interact with other activator proteins.

PMID- 20048338
TI  - Functional interplay between LIS1, NDE1 and NDEL1 in dynein-dependent organelle
      positioning.
AB  - LIS1, NDE1 and NDEL1 modulate cytoplasmic dynein function in several cellular
      contexts. However, evidence that they regulate dynein-dependent organelle
      positioning is limited. Here, we show that depletion of NDE1 or NDEL1 alone
      profoundly affected the organisation of the Golgi complex but did not cause it to
      disperse, and slightly affected the position of endocytic compartments. However,
      striking dispersal of organelles was observed when both NDE1 and NDEL1 were
      depleted. A substantial portion of NDE1 and NDEL1 is membrane associated, and
      depletion of these proteins led to complete loss of dynein from membranes.
      Knockdown of LIS1 also caused the Golgi complex to fragment and disperse
      throughout the cell, and caused endocytic compartments to relocalise to the
      periphery. Depletion of LIS1, which is primarily cytosolic, led to partial loss
      of membrane-associated dynein, without affecting NDE1 and NDEL1. These data
      suggest that NDE1 and NDEL1 act upstream of LIS1 in dynein recruitment, and/or
      activation, on the membrane. Consistent with this hypothesis, expression of
      exogenous NDE1 or NDEL1 rescued the effects of LIS1 depletion on Golgi
      organisation, whereas LIS1 was only partially effective at rescuing the loss of
      NDE1 and NDEL1.

PMID- 20048339
TI  - Canonical Notch signaling in the developing lung is required for determination of
      arterial smooth muscle cells and selection of Clara versus ciliated cell fate.
AB  - Lung development is the result of complex interactions between four tissues:
      epithelium, mesenchyme, mesothelium and endothelium. We marked the lineages
      experiencing Notch1 activation in these four cellular compartments during lung
      development and complemented this analysis by comparing the cell fate choices
      made in the absence of RBPjkappa, the essential DNA binding partner of all Notch
      receptors. In the mesenchyme, RBPjkappa was required for the recruitment and
      specification of arterial vascular smooth muscle cells (vSMC) and for regulating
      mesothelial epithelial-mesenchymal transition (EMT), but no adverse affects were
      observed in mice lacking mesenchymal RBPjkappa. We provide indirect evidence that
      this is due to vSMC rescue by endothelial-mesenchymal transition (EnMT). In the
      epithelium, we show that Notch1 activation was most probably induced by Foxj1
      expressing cells, which suggests that Notch1-mediated lateral inhibition
      regulates the selection of Clara cells at the expense of ciliated cells.
      Unexpectedly, and in contrast to Pofut1-null epithelium, Hes1 expression was only
      marginally reduced in RBPjkappa-null epithelium, with a corresponding minimal
      effect on pulmonary neuroendocrine cell fate selection. Collectively, the primary
      roles for canonical Notch signaling in lung development are in selection of Clara
      cell fate and in vSMC recruitment. These analyses suggest that the impact of
      gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous
      contribution from endothelial or vSMC-derived signals.

PMID- 20048340
TI  - CDC6 interaction with ATR regulates activation of a replication checkpoint in
      higher eukaryotic cells.
AB  - CDC6, a replication licensing protein, is partially exported to the cytoplasm in
      human cells through phosphorylation by Cdk during S phase, but a significant
      proportion remains in the nucleus. We report here that human CDC6 physically
      interacts with ATR, a crucial checkpoint kinase, in a manner that is stimulated
      by phosphorylation by Cdk. CDC6 silencing by siRNAs affected ATR-dependent
      inhibition of mitotic entry elicited by modest replication stress. Whereas a Cdk
      phosphorylation-mimicking CDC6 mutant could rescue the checkpoint defect by CDC6
      silencing, a phosphorylation-deficient mutant could not. Furthermore, we found
      that the CDC6-ATR interaction is conserved in Xenopus. We show that the presence
      of Xenopus CDC6 during S phase is essential for Xenopus ATR to bind to chromatin
      in response to replication inhibition. In addition, when human CDC6 amino acid
      fragment 180-220, which can bind to both human and Xenopus ATR, was added to
      Xenopus egg extracts after assembly of the pre-replication complex, Xenopus Chk1
      phosphorylation was significantly reduced without lowering replication, probably
      through a sequestration of CDC6-mediated ATR-chromatin interaction. Thus, CDC6
      might regulate replication-checkpoint activation through the interaction with ATR
      in higher eukaryotic cells.

PMID- 20048341
TI  - Neuronal low-density lipoprotein receptor-related protein 1 binds and endocytoses
      prion fibrils via receptor cluster 4.
AB  - For infectious prion protein (designated PrP(Sc)) to act as a template to convert
      normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the
      two forms of prion protein (PrP) must interact closely. The neuronal receptor
      that rapidly endocytoses PrP(C) is the low-density lipoprotein receptor-related
      protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor
      that binds and rapidly endocytoses smaller oligomeric forms of infectious prion
      fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most
      ligands independently to its receptor clusters 2 and 4, PrP(C) and PrP(Sc)
      fibrils bind only to receptor cluster 4. PrP(Sc) fibrils out-compete PrP(C) for
      internalization. When endocytosed, PrP(Sc) fibrils are routed to lysosomes,
      rather than recycled to the cell surface with PrP(C). Thus, although LRP1 binds
      both forms of PrP, it traffics them to separate fates within sensory neurons. The
      binding of both to ligand cluster 4 should enable genetic modification of PrP
      binding without disrupting other roles of LRP1 essential to neuronal viability
      and function, thereby enabling in vivo analysis of the role of this interaction
      in controlling both prion and LRP1 biology.

PMID- 20048342
TI  - Caspase-1 targets the TLR adaptor Mal at a crucial TIR-domain interaction site.
AB  - Toll-like receptors (TLRs) are crucial components of innate immunity, ensuring
      efficient responses against invading pathogens. After ligand binding, TLR
      signaling is initiated by recruitment of adaptor molecules, a step mediated by
      homotypic Toll-IL-1 receptor (TIR) domain interactions. Four TIR-containing TLR
      adaptor molecules are described, all of which are susceptible to modification and
      strict regulation. For example, caspase-1 is reported to cleave the TLR adaptor
      Mal at position D198, an event that is indispensible for Mal function. In this
      report, we use the mammalian two-hybrid technique MAPPIT to study the
      implications of Mal cleavage. We show that a Mal mutant, which mimics caspase-1
      cleavage and a caspase-1-uncleavable MalD198A mutant, are abrogated in their
      bridging function and lose the ability to activate NF-kappaB. A MalD198E mutant
      is still fully functional, suggesting that caspase-1 cleavage of Mal is not
      necessary for Mal-mediated signaling. D198 of Mal is conserved in MyD88 and TLR4
      TIR domains and the negatively charged amino acid at this position is crucial for
      the interactions and function of Mal, MyD88 and TLR4 TIR. Our data suggest an
      inhibitory, rather than an activating role for caspase-1 in Mal regulation, and
      show that the caspase-1 cleavage site in Mal is part of a TIR-domain interaction
      site.

PMID- 20048343
TI  - E-cadherin-mediated survival of androgen-receptor-expressing secretory prostate
      epithelial cells derived from a stratified in vitro differentiation model.
AB  - The androgen receptor (AR) is expressed in differentiated secretory prostate
      epithelial cells in vivo. However, in the human prostate, it is unclear whether
      androgens directly promote the survival of secretory cells, or whether secretory
      cells survive through androgen-dependent signals from the prostate stroma.
      Biochemical and mechanistic studies have been hampered by inadequate cell-culture
      models. In particular, large-scale differentiation of prostate epithelial cells
      in culture has been difficult to achieve. Here, we describe the development of a
      differentiation system that is amenable to functional and biochemical analysis
      and its application to deciphering the survival pathways in differentiated AR
      expressing epithelial cells. Confluent prostate epithelial cell cultures were
      treated with keratinocyte growth factor (KGF) and dihydrotestosterone. After 2
      weeks, a suprabasal cell layer was formed in which cells no longer expressed
      alpha2, alpha3, alpha6, alphav, beta1 or beta4 integrins or p63, K5, K14, EGFR,
      FGFR2IIIb or Bcl-2, but instead expressed AR and androgen-induced differentiation
      markers, including K18, K19, TMPRSS2, Nkx3.1, PMSA, KLK2 and secreted prostate
      specific antigen (PSA). Differentiated prostate cell survival depended on E
      cadherin and PI3K, but not KGF, androgen, AR or MAPK. Thus survival of
      differentiated prostate epithelial cells is mediated by cell-cell adhesion, and
      not through androgen activity or prostate stroma-derived KGF.

PMID- 20048344
TI  - The cell adhesion molecule Roughest depends on beta(Heavy)-spectrin during eye
      morphogenesis in Drosophila.
AB  - Cell junctions have both structural and morphogenetic roles, and contain complex
      mixtures of proteins whose interdependencies are still largely unknown. Junctions
      are also major signaling centers that signify correct integration into a tissue,
      and modulate cell survival. During Drosophila eye development, the activity of
      the immunoglobulin cell adhesion molecule Roughest (also known as Irregular
      chiasm C-roughest protein) mediates interommatidial cell (IOC) reorganization,
      leading to an apoptotic event that refines the retinal lattice. Roughest and the
      cadherin-based zonula adherens (ZA) are interdependent and both are modulated by
      the apical polarity determinant, Crumbs. Here we describe a novel relationship
      between the Crumbs partner beta(Heavy)-spectrin (beta(H)), the ZA and Roughest.
      Ectopic expression of the C-terminal segment 33 of beta(H) (betaH33) induces
      defects in retinal morphogenesis, resulting the preferential loss of IOC. This
      effect is associated with ZA disruption and Roughest displacement. In addition,
      loss-of-function karst and roughest mutations interact to cause a synergistic and
      catastrophic effect on retinal development. Finally, we show that beta(H)
      coimmunoprecipitates with Roughest and that the distribution of Roughest protein
      is disrupted in karst mutant tissue. These results suggest that the apical
      spectrin membrane skeleton helps to coordinate the Cadherin-based ZA with
      Roughest-based morphogenesis.

PMID- 20048345
TI  - Humanized SFTPA1 and SFTPA2 transgenic mice reveal functional divergence of SP-A1
      and SP-A2: formation of tubular myelin in vivo requires both gene products.
AB  - Surfactant protein A (SP-A) plays a role in lung innate immunity and surfactant
      related functions. Two functional genes, SP-A1 (SFTPA1) and SP-A2 (SFTPA2), are
      present in humans and primates (rodents have one gene). Single gene SP-A1 or SP
      A2 proteins expressed in vitro are functional. To study their role in vivo, we
      generated humanized transgenic (hTG) C57BL/6 mice, SP-A1(6A(4)) and SP-A2(1A(3)).
      The SP-A cDNA in experimental constructs was driven by the 3.7-kb SP-C promoter.
      Positive hTG mice were bred with SP-A knock-out mice to generate F8 offspring for
      study. Epithelial alveolar type II cells were SP-A-positive, and Clara cells were
      negative by immunohistochemistry in hTG mice. The levels of SP-A in lungs of two
      hTG lines used were comparable with those in human lungs. Southern blot analysis
      indicated that two cDNA copies of either SP-A1(6A(4)) or SP-A2(1A(3)) were
      integrated as a concatemer into the genome of each of the two hTG lines. Electron
      microscopy analysis revealed that hTG mice with a single SP-A1(6A(4)) or SP
      A2(1A(3)) gene product lacked tubular myelin (TM), but hTG mice carrying both had
      TM. Furthermore, TM was observed in human bronchoalveolar lavage fluid only if
      both SP-A1 and SP-A2 gene products were present and not in those containing
      primarily (>99.7%) either SP-A1 or SP-A2 gene products. In vivo rescue study
      confirmed that TM can only be restored after administering exogenous SP-A
      containing both SP-A1 and SP-A2 into the lungs of SP-A knock-out mice. These
      observations indicate that SP-A1 and SP-A2 diverged functionally at least in
      terms of TM formation.

PMID- 20048346
TI  - Time is moving on.... a moment to reflect.

PMID- 20048347
TI  - Current perceptions of respite care: experiences of family and informal carers of
      people with a learning disability.
AB  - Access to regular, high-quality respite care has a beneficial impact on a carer's
      ability to fulfil their caring role, but provision varies widely. The current
      study aims to report family and informal carers' perceptions of respite care
      services offered to them by their local authority. A mixed method, triangulated
      design, yielded both quantitative and qualitative data. Members of a parent/carer
      federation were sent a questionnaire which included a section on 'respite care';
      151 of 647 responded. Two focus groups were held with 15 carers who had
      previously completed the questionnaire. The majority of carers reported that
      their respite needs were not being met. Unmet needs were hampered by the lack of
      information regarding criteria for access to respite. Discrepancies were evident
      between professionals and carers on a shared definition of respite care. Carers
      were unsure of exactly which activities constituted respite care and for whom the
      service was being provided.

PMID- 20048348
TI  - Impact of parents' involvement and engagement in a learning readiness programme
      for children with severe and profound intellectual disability and complex needs
      in India.
AB  - Cognitive, social, motor and language skills are key factors that contribute to
      the quality of life for people with learning disabilities and for their carers.
      Development of these skills for children with severe learning disabilities who
      have other complex needs however remains a challenge. A pilot study was
      undertaken by the staff from The Jai Vakeel School for Children in Need of
      Special Care, Mumbai, with a view to examining the effects of training offered by
      parents of children with severe learning disabilities and complex needs on their
      emotional, social, language, cognitive and motor skill development. Using a
      Parental Involvement/Engagement Scale it was seen that children with lower
      parental involvement had less improvement in the above areas whilst children with
      higher parental involvement showed greater improvement. The findings are
      discussed in relation to the hypothesis that the pre-clinical condition of the
      child will affect the outcome of therapy.

PMID- 20048349
TI  - Education and training for learning disability practice: key messages from
      contemporary literature.
AB  - Over the last quarter of a century, much attention has justifiably been given to
      the closure of long-stay hospitals and the subsequent community-based experiences
      of people with learning disabilities. This has inevitably led to debate regarding
      how best they might continue to be supported, and by whom. Having identified a
      range of accredited provision currently available to prepare or develop staff
      working with adults with learning disabilities in the United Kingdom, this
      article reviews a range of contemporary literature relating to education in
      learning disability health and social care that is typically produced and viewed
      in isolation. Four themes are identified: training social carers, user
      involvement, (inter)professional practice and work-based learning. Key messages
      emerge from these themes to form recommendations for the future education of
      learning disability practitioners across the workforce.

PMID- 20048350
TI  - Do individuals with schizophrenia and a borderline intellectual disability
      benefit from psychoeducational groups?
AB  - Studies on psychoeducation in schizophrenia demonstrate significant effects on
      rehospitalization rates, compliance and knowledge. Within the framework of the
      Munich COGPIP study we examined whether borderline intellectual disability in
      patients with schizophrenia limits the benefit from psychoeducational groups. A
      total of 116 inpatients with schizophrenic or schizoaffective disorders were
      recruited for the COGPIP study. A manualized, interactive psychoeducational
      programme of eight sessions (4 weeks) was initiated. Measures of knowledge,
      adherence and the concept of illness were completed before and after the groups.
      The short-term outcome of 22 participants with schizophrenia and borderline
      intellectual disability (IQ 70-85) was compared with the outcome of 75
      participants with schizophrenia and IQ > 85. Results showed that individuals with
      schizophrenia and borderline intellectual disability could be successfully
      integrated into general psychoeducational groups. The conclusion is that
      borderline intellectual disability should not be an exclusion criterion for
      participation in such groups.

PMID- 20048351
TI  - Listening to women with intellectual disabilities and mental health problems: a
      focus on risk and resilient factors.
AB  - Women without intellectual disabilities are more likely to develop mental health
      problems as a result of physiological functioning and psychosocial risk factors.
      However, little is known about the mental health of women with intellectual
      disabilities. The aim of this study was to explore a small group of women's
      perceptions of the risk and protective factors pertaining to their mental health
      conditions. Twelve semi-structured interviews were conducted in 2007 in Northern
      Ireland. Thematic content analysis identified three risk factors and four
      protective/resilient factors. None of the women identified physiological
      functioning as a risk factor. Results suggest that women with intellectual
      disabilities experience psychosocial risk factors similar to those reported by
      women without intellectual disability. Additional risk factors place them at
      higher risk of developing mental health problems. However, more research is
      required.

PMID- 20048353
TI  - Long-term care legislation at long last?

PMID- 20048355
TI  - Long-term care: who gets it, who provides it, who pays, and how much?
AB  - Long-term care in the United States is needed by 10.9 million community
      residents, half of them nonelderly, and 1.8 million nursing home residents,
      predominantly elderly. Ninety-two percent of community residents receive unpaid
      help, while 13 percent receive paid help. Paid community-based long-term care
      services are primarily funded by Medicaid or Medicare, while nursing home stays
      are primarily paid for by Medicaid plus out-of-pocket copayments. Per person
      expenditures are five times as high, and national expenditures three times as
      high, for nursing home residents compared to community residents. This suggests
      that a redistribution of spending across care settings might produce substantial
      savings or permit service expansions.

PMID- 20048356
TI  - Medicare and medicaid in long-term care.
AB  - Medicare and Medicaid, two publicly funded health programs, both cover
      populations in need of long-term care, but they are poorly coordinated. Gaps
      often exist in some services while there is overlap in others. This can lead to
      inefficient delivery of services and confusion among program recipients and
      providers alike. Spending on postacute services in Medicare and long-term care
      services in Medicaid has grown more rapidly than enrollment in either program
      since 1999. Although growing numbers of people receive home and community-based
      services paid for by the two programs, there are wide variations across states
      and among target groups. The system of long-term care is in need of structural
      reform.

PMID- 20048357
TI  - The accumulated challenges of long-term care.
AB  - During the past century, long-term care in the United States has evolved through
      five cycles of development, each lasting approximately twenty years. Each,
      focusing on distinct concerns, produced unintended consequences. Each also added
      a layer to an accumulation of contradictory approaches--a patchwork system now
      pushed to the breaking point by increasing needs and financial pressures. Future
      policies must achieve a better synthesis of approaches inherited from the past,
      while addressing their unintended consequences. Foremost must be assuring access
      to essential care, delivery of high-quality services in an increasingly
      deinstitutionalized system, and a reduction in social and economic disparities.

PMID- 20048358
TI  - Sizing up the market for assisted living.
AB  - Assisted living has emerged as an important housing and long-term care option for
      older Americans. To date, development of this sector has occurred largely without
      government financing or regulation. In this study we used primary data that we
      collected on county-level assisted living supply to gain a fuller understanding
      of this sector nationally. Reflecting their reliance on private resources,
      assisted living facilities are located disproportionately in areas with higher
      educational attainment, income, and housing wealth. As this sector evolves,
      policymakers will have to contend with issues related to access to services,
      public financing, quality of care, and regulatory oversight.

PMID- 20048359
TI  - Diversion, transition programs target nursing homes' status quo.
AB  - As millions of Americans age and exercise their preference for long-term care in
      the least restrictive environment, policymakers search for ways to increase
      community-based services. A new federal program--Money Follows the Person--is off
      to a slow but promising start. The program's "downstream" approach moves
      residents out of nursing homes and into community care settings. For example,
      states with mature nursing home transition programs have managed to relocate 25
      35 percent of their nursing home residents to assisted living. Other programs
      successfully using "upstream" strategies to keep people out of nursing homes have
      not been widely copied. The challenge for policymakers is to maintain funding and
      flexibility so that nursing homes are no longer the default option for older
      adults and people with disabilities.

PMID- 20048360
TI  - New state strategies to meet long-term care needs.
AB  - Consumer-directed long-term care service programs give participants the
      flexibility they want, while reducing unmet need for home and community-based
      services and supports. States' efforts to expand such programs under Medicaid,
      including those supported by federal Cash and Counseling demonstration and
      evaluation grants, are often hindered by challenges related to costs, staffing
      and organizational issues, new infrastructure requirements, and resistance from
      stakeholders. Yet states have developed a number of successful strategies for
      overcoming these challenges, even in financially trying times. Their experiences
      offer valuable insights, guidance, and encouragement to other states
      contemplating consumer-directed service expansions.

PMID- 20048361
TI  - The revolving door of rehospitalization from skilled nursing facilities.
AB  - Almost one-fourth of Medicare beneficiaries discharged from the hospital to a
      skilled nursing facility were readmitted to the hospital within thirty days; this
      cost Medicare $4.34 billion in 2006. Especially in an elderly population, cycling
      into and out of hospitals can be emotionally upsetting and can increase the
      likelihood of medical errors related to care coordination. Payment incentives in
      Medicare do not encourage providers to coordinate beneficiaries' care. Revising
      these incentives could achieve major savings for providers and improved quality
      of life for beneficiaries.

PMID- 20048362
TI  - Elderly hispanics more likely to reside in poor-quality nursing homes.
AB  - The proportion of Hispanics age sixty-five and older who are living in nursing
      homes rose from 5 percent in 2000 to 6.4 percent in 2005. Although segregation in
      nursing homes seems to have declined slightly, elderly Hispanics are more likely
      than their non-Hispanic white peers to reside in nursing homes that are
      characterized by severe deficiencies in performance, understaffing, and poor
      care.

PMID- 20048363
TI  - Applying market-based reforms to long-term care.
AB  - Recent trends in U.S. long-term care policy reflect three broad goals Americans
      have for the quality of long-term care: improving quality of life, reducing
      fragmentation of delivery and financing, and increasing use of home and community
      based care. At the same time, market-based reforms--namely, public reporting and
      pay-for-performance--have taken on their own momentum, aimed at improving the
      clinical quality of care among nursing home and home health care providers. The
      focus of reporting systems should be broadened to include quality of life in
      addition to clinical quality and to make measures less dependent on the setting
      in which care is delivered.

PMID- 20048364
TI  - Advancing nursing home quality through quality improvement itself.
AB  - The traditional approaches to improving the quality of care at U.S. nursing homes
      -regulation, inspection, and accountability through public reporting--have
      produced modest results. Greater progress could be made by focusing incentives on
      broader processes related to improving quality. This could foster a culture of
      upstream identification and solving of problems that would supplement existing
      downstream requirements to meet specific safety and care standards.

PMID- 20048365
TI  - Lessons from public long-term care insurance in Germany and Japan.
AB  - The U.S. Congress is considering the Community Living Assistance Services and
      Supports (CLASS) Act, a voluntary insurance program that would help pay for long
      term services and supports to disabled Americans. In Germany and Japan, social
      insurance programs are universal, support family caregivers, and allow
      individuals considerable flexibility in securing the services they require. We
      explored differences between Germany and Japan in program goals, eligibility
      process, scope, size, and sustainability for possible applications in the United
      States. Moreover, when we compared public spending on long-term care, we found
      that spending in the United States is actually higher than in Germany even now,
      prior to enactment of the CLASS Act, and is only slightly lower than in Japan.

PMID- 20048366
TI  - The complementarity of public and private long-term care coverage.
AB  - Discussions about long-term care financing often get mired in the false dichotomy
      that long-term care should be primarily either a public or a private
      responsibility. Our starting premise is that public and private long-term care
      coverage can best serve complementary roles. Therefore, public policy should
      focus on supporting both mechanisms to achieve efficient and equitable outcomes.
      The current state of the private long-term care insurance market, and the
      possible reasons for its modest size, provide a starting point for exploring how
      public policy might interface more productively with it, in the context of both
      existing and potential programs, such as the proposed Community Living Assistance
      Services and Supports (CLASS) Act.

PMID- 20048368
TI  - Improving the long-term care workforce serving older adults.
AB  - There is a worsening shortage of competent, committed, paid long-term care
      workers who are able to meet the needs of older adults. Efforts to address the
      shortage must be informed by a conceptual framework that acknowledges the unique
      circumstances affecting these workers. These include nontraditional market
      forces, low compensation and prestige, limited career opportunities, and
      inadequate preparation for evolving roles and responsibilities. Applying this
      framework, we identify strategies that can reverse current trends by expanding
      worker supply; improving education, training, and developmental activities; and
      making delivery of long-term care services and supports to older people a more
      attractive alternative to employment in acute and primary care settings.

PMID- 20048367
TI  - Genetic testing for Alzheimer's and long-term care insurance.
AB  - A genetic marker known as apolipoprotein E provides a clear signal of a person's
      risk of developing Alzheimer's disease and thus that person's future need for
      long-term care. People who find that they have the variant of the trait that
      increases Alzheimer's disease risk are more likely to purchase long-term care
      insurance after receiving this information. If the information is widely
      introduced into the insurance market, coverage rates could be affected in
      different ways, depending on who possesses that information. Policymakers will
      eventually need to confront the issue of the use of this and other markers in the
      pricing of long-term care insurance.

PMID- 20048369
TI  - Bridging troubled waters: family caregivers, transitions, and long-term care.
AB  - Families are the bedrock of long-term care, but policymakers have traditionally
      considered them "informal" caregivers, as they are not part of the formal paid
      caregiving workforce. As chronic and long-term care systems have become more
      complex and as more demanding tasks have been shifted to families, this view is
      no longer sustainable. The care transition process offers a critical opportunity
      to treat family caregivers as important care partners. Enhancing their
      involvement, training, and support will contribute to reducing unnecessary
      rehospitalizations and improving patient outcomes. The contributions and
      experiences of family caregivers should be considered in gathering information to
      shape policies and practice; training health care professionals; developing
      programs; and reforming financing.

PMID- 20048370
TI  - The faces of home care.

PMID- 20048371
TI  - A new medicare end-of-life benefit for nursing home residents.
AB  - Many elderly people spend their final days in nursing homes. For them, high
      quality end-of-life care is an important component of their overall care.
      Unfortunately, the Medicare hospice benefit-the primary source of palliative care
      coverage for Medicare beneficiaries-is a poor fit with the nursing home setting.
      We recommend creating a separate end-of-life Medicare benefit for nursing home
      residents based on documented need for services that neither requires physicians
      to certify a person's prognosis, nor requires beneficiaries to choose it or to
      agree to forgo curative care. Nursing homes would be paid directly for end-of
      life care services and held accountable for their quality.

PMID- 20048372
TI  - Raising the standard: palliative care in nursing homes.
AB  - More than two-thirds of long-stay nursing home residents suffer from dementia.
      This illness has a variable and unpredictable course that renders it a poor fit
      for the six-month life-expectancy requirement of the Medicare hospice benefit.
      Palliative care-a form of treatment that strives to match care to patient goals,
      relieve pain, and improve quality of life for people with chronic or life
      threatening illnesses-should be the standard of practice for all elderly dementia
      patients in nursing homes, regardless of prognosis. Similar principles could
      apply to other long-term residents with underlying chronic diseases who would
      benefit from palliative care. Indeed, we would argue that the growing acceptance
      of the culture-change movement centered on elder-directed goals in nursing homes
      is promising evidence of the goodness-of-fit of palliative care principles in the
      long-term care setting.

PMID- 20048373
TI  - End of life: a workplace issue.
AB  - Many employers have not placed a priority on addressing end-of-life issues. Yet
      these issues affect their employees who serve as caregivers to ailing parents and
      siblings, who experience a health crisis for themselves or a partner, or who care
      for a critically ill child. End-of life issues affect employers' cost of
      benefits, workers' productivity, and absentee and "presenteeism" rates, and they
      can undermine employees' effectiveness at work. Some employers have begun to
      address end-of-life issues with targeted programs and are gathering data to
      evaluate their impacts. Potential solutions include using existing resources;
      training managers to assist employees in need; and monitoring the costs of end-of
      life challenges. In an environment where end-of-life issues are politically
      charged, employers must clearly communicate their motives to workers and assure
      them that end-of-life resources have beneficial intent.

PMID- 20048374
TI  - Health spending growth at a historic low in 2008.
AB  - In 2008, U.S. health care spending growth slowed to 4.4 percent--the slowest rate
      of growth over the past forty-eight years. The deceleration was broadly based for
      nearly all payers and health care goods and services, as growth in both price and
      nonprice factors slowed amid the recession. Despite the slowdown, national health
      spending reached $2.3 trillion, or $7,681 per person, and the health care portion
      of gross domestic product (GDP) grew from 15.9 percent in 2007 to 16.2 percent in
      2008. These developments reflect the general pattern that larger increases in the
      health spending share of GDP generally occur during or just after periods of
      economic recession. Despite the overall slowdown in national health spending
      growth, increases in this spending continue to outpace growth in the resources
      available to pay for it.

PMID- 20048376
TI  - Physician orders contribute to high-tech imaging slowdown.
AB  - The utilization rate of advanced diagnostic imaging (magnetic resonance imaging,
      computed tomography, and nuclear medicine) in Medicare outpatients rose 72.7
      percent between 2000 and 2005, sparking concern among policymakers. However,
      analysis of discretionary use of these exams indicates that their use largely
      stabilized after 2005. Some have credited the Deficit Reduction Act of 2005,
      which sharply reduced reimbursements for advanced imaging done in physicians'
      offices. But the fact that the leveling was more pronounced in hospital
      outpatient facilities than in physicians' offices indicates that the explanation
      lies elsewhere. More likely, there has been a change in physicians' ordering
      patterns, possibly due to the influence of radiology business management
      companies (RBMs) and imaging guidelines promulgated by specialty societies.

PMID- 20048378
TI  - The loneliness of fighting a rare cancer.
AB  - After her mother is diagnosed with gallbladder cancer, a journalist researches
      how to help find effective therapies for patients who get rare diseases.

PMID- 20048377
TI  - Cancer therapy costs influence treatment: a national survey of oncologists.
AB  - A national survey of medical oncologists indicates that rising cancer treatment
      costs are influencing clinical practice, even as oncologists tend not to
      communicate with patients about costs. The survey shows that 84 percent of
      oncologists say that patients' out-of-pocket spending influences treatment
      recommendations. Only 43 percent always or frequently discuss costs with
      patients. Among those surveyed, 79 percent favor more comparative effectiveness
      research; 80 percent support more cost-effectiveness data, although only 42
      percent feel well prepared to interpret it. The results suggest that physicians
      support federally funded comparative effectiveness research but that they wish to
      retain a central role in making decisions about how and when to use expensive
      cancer treatments. The results also support educating physicians about cost
      effectiveness and how to communicate with patients regarding cost.

PMID- 20048379
TI  - Foundation work in long-term care.
AB  - Health foundations have invested in services, research, and advocacy to improve
      the financing and delivery of long-term services and supports. This article
      describes some of the broad array of approaches they have taken--in such areas as
      aging in place, assisted living, "culture change" in nursing homes, quality
      improvement, augmenting the workforce, and paying for care.

PMID- 20048380
TI  - Calorie labeling and obesity.

PMID- 20048382
TI  - Microarrays.

PMID- 20048381
TI  - Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism
      for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic
      hamsters.
AB  - We investigated the role of proprotein convertase subtilisin/kexin type 9 (PCSK9)
      in the resistance of dyslipidemic hamsters to statin-induced LDL-cholesterol (LDL
      C) reduction and the molecular mechanism by which statins modulated PCSK9 gene
      expression in vivo. We utilized the fructose diet-induced dyslipidemic hamsters
      as an in vivo model and rosuvastatin to examine its effects on liver PCSK9 and
      LDL receptor (LDLR) expression and serum lipid levels. We showed that
      rosuvastatin induced PCSK9 mRNA to a greater extent than LDLR mRNA in the hamster
      liver. The net result was that hepatic LDLR protein level was reduced. This
      correlated closely with an increase in serum LDL-C with statin treatment. More
      importantly, we demonstrated that in addition to an increase in sterol response
      element binding protein 2 (SREBP2) expression, rosuvastatin treatment increased
      the liver expression of hepatocyte nuclear factor 1 alpha (HNF1alpha), the newly
      identified key transactivator for PCSK9 gene expression. Our study suggests that
      the inducing effect of rosuvastatin on HNF1alpha is likely a underlying mechanism
      accounting for the higher induction of PCSK9 than LDLR because of the utilization
      of two transactivators (HNF1alpha and SREBP2) in PCSK9 transcription versus one
      (SREBP2) in LDLR transcription. Thus, the net balance is in favor of PCSK9
      induced degradation of LDLR in the hamster liver, abrogating the effect of
      rosuvastatin on LDL-C lowering.

PMID- 20048383
TI  - A review of statistical methods for preprocessing oligonucleotide microarrays.
AB  - Microarrays have become an indispensable tool in biomedical research. This
      powerful technology not only makes it possible to quantify a large number of
      nucleic acid molecules simultaneously, but also produces data with many sources
      of noise. A number of preprocessing steps are therefore necessary to convert the
      raw data, usually in the form of hybridisation images, to measures of biological
      meaning that can be used in further statistical analysis. Preprocessing of
      oligonucleotide arrays includes image processing, background adjustment, data
      normalisation/transformation and sometimes summarisation when multiple probes are
      used to target one genomic unit. In this article, we review the issues
      encountered in each preprocessing step and introduce the statistical models and
      methods in preprocessing.

PMID- 20048384
TI  - Multiple testing and its applications to microarrays.
AB  - The large-scale multiple testing problems resulting from the measurement of
      thousands of genes in microarray experiments have received increasing interest
      during the past several years. This article describes some commonly used criteria
      for controlling false positive errors, including familywise error rates, false
      discovery rates and false discovery proportion rates. Various statistical methods
      controlling these error rates are described. The advantages and disadvantages of
      these methods are discussed. These methods are applied to gene expression data
      from two microarray studies and the properties of these multiple testing
      procedures are compared.

PMID- 20048385
TI  - Gene set enrichment analysis made simple.
AB  - Among the many applications of microarray technology, one of the most popular is
      the identification of genes that are differentially expressed in two conditions.
      A common statistical approach is to quantify the interest of each gene with a p
      value, adjust these p-values for multiple comparisons, choose an appropriate cut
      off, and create a list of candidate genes. This approach has been criticised for
      ignoring biological knowledge regarding how genes work together. Recently a
      series of methods, that do incorporate biological knowledge, have been proposed.
      However, the most popular method, gene set enrichment analysis (GSEA), seems
      overly complicated. Furthermore, GSEA is based on a statistical test known for
      its lack of sensitivity. In this article we compare the performance of a simple
      alternative to GSEA. We find that this simple solution clearly outperforms GSEA.
      We demonstrate this with eight different microarray datasets.

PMID- 20048386
TI  - Prior biological knowledge-based approaches for the analysis of genome-wide
      expression profiles using gene sets and pathways.
AB  - An increasing challenge in analysis of microarray data is how to interpret and
      gain biological insight of profiles of thousands of genes. This article provides
      a review of statistical methods for analysis of microarray data by incorporating
      prior biological knowledge using gene sets and biological pathways, which consist
      of groups of biologically similar genes. We first discuss issues of individual
      gene analysis. We compare several methods for analysis of gene sets including
      over-representation anlaysis, gene set enrichment analysis, principal component
      analysis, global test and kernel machine. We discuss the assumptions of these
      methods and their pros and cons. We illustrate these methods by application to a
      type II diabetes data set.

PMID- 20048387
TI  - Reconstructing transcriptional regulatory networks through genomics data.
AB  - One central problem in biology is to understand how gene expression is regulated
      under different conditions. Microarray gene expression data and other high
      throughput data have made it possible to dissect transcriptional regulatory
      networks at the genomics level. Owing to the very large number of genes that need
      to be studied, the relatively small number of data sets available, the noise in
      the data and the different natures of the distinct data types, network inference
      presents great challenges. In this article, we review statistical and
      computational methods that have been developed in the last decade in response to
      genomics data for inferring transcriptional regulatory networks.

PMID- 20048388
TI  - Multiple Escherichia coli RecQ helicase monomers cooperate to unwind long DNA
      substrates: a fluorescence cross-correlation spectroscopy study.
AB  - The RecQ family helicases catalyze the DNA unwinding reaction in an ATP
      hydrolysis-dependent manner. We investigated the mechanism of DNA unwinding by
      the Escherichia coli RecQ helicase using a new sensitive helicase assay based on
      fluorescence cross-correlation spectroscopy (FCCS) with two-photon excitation.
      The FCCS-based assay can be used to measure the unwinding activity under both
      single and multiple turnover conditions with no limitation related to the size of
      the DNA strands constituting the DNA substrate. We found that the monomeric
      helicase was sufficient to perform the unwinding of short DNA substrates.
      However, a significant increase in the activity was observed using longer DNA
      substrates, under single turnover conditions, originating from the simultaneous
      binding of multiple helicase monomers to the same DNA molecule. This functional
      cooperativity was strongly dependent on several factors, including DNA substrate
      length, the number and size of single-stranded 3'-tails, and the temperature.
      Regarding the latter parameter, a strong cooperativity was observed at 37 degrees
      C, whereas only modest or no cooperativity was observed at 25 degrees C
      regardless of the nature of the DNA substrate. Consistently, the functional
      cooperativity was found to be tightly associated with a cooperative DNA binding
      mode. We also showed that the cooperative binding of helicase to the DNA
      substrate indirectly accounts for the sigmoidal dependence of unwinding activity
      on ATP concentration, which also occurs only at 37 degrees C but not at 25
      degrees C. Finally, we further examined the influences of spontaneous DNA
      rehybridization (after helicase translocation) and the single-stranded DNA
      binding property of helicase on the unwinding activity as detected in the FCCS
      assay.

PMID- 20048389
TI  - The relative effects of abciximab and tirofiban on platelet inhibition and C
      reactive protein during coronary intervention.
AB  - BACKGROUND: We sought to compare the efficacy of tirofiban and abciximab on
      platelet inhibition as well as their effects of platelet inhibition on C-reactive
      protein levels during percutaneous coronary intervention (PCI). METHODS: Using a
      randomized, double-blind study design, 95 consecutively eligible patients were
      randomized to receive either tirofiban or abciximab before undergoing native
      coronary artery revascularization with a stent. Clinical endpoints were death,
      nonfatal MI, target vessel revascularization (TVR) with coronary artery bypass
      grafting or PCI within 30 days of the study procedure. The medications were
      compared for differences in platelet aggregation as measured by a rapid function
      platelet assay, as well as measurements of the inflammatory marker C-reactive
      protein (CRP) at frequent intervals following drug administration during PCI.
      RESULTS: A total of 95 patients were randomized to abciximab (n = 44) or
      tirofiban (n= 51). There was no significant difference in platelet aggregation
      documented throughout the procedure (10-, 20-, 30-, 45-minute time points). In
      diabetic patients abciximab had significantly lower platelet inhibition as
      compared to tirofiban at 10 minutes (84.17 +/- 8.28% vs. 90.40 +/- 5.79%; p =
      0.0097). Using a Spearman correlation coefficient model, hs-CRP demonstrated an
      inverse relationship with platelet inhibition over time (-0.7307, p = 0.0002) in
      patients treated with abciximab. CONCLUSION: There is no major difference in
      platelet inhibition between tirofiban and abciximab during PCI. In this study,
      tirofiban showed a greater inhibition in diabetic subsets at the first time point
      within PCI. Platelet inhibition may be inversely related to the levels of CRP
      during PCI.

PMID- 20048390
TI  - Measuring the right compound at the right time is not always easy.

PMID- 20048391
TI  - Increased vascular access complications in patients with renal dysfunction
      undergoing percutaneous coronary procedures using arteriotomy closure devices.
AB  - BACKGROUND: Arteriotomy closure device (ACD) use has increased following
      percutaneous transfemoral coronary procedures (PTCP). However, their safety in
      patients with chronic kidney disease (CKD) is not known. Therefore, we evaluated
      the complication rates of ACD among patients with CKD. METHODS: Six-hundred ten
      consecutive patients who underwent PTCP and ACD were retrospectively studied.
      Patients were grouped according to their creatinine clearance (CrCl in
      ml/min/1.73 m2) calculated by the Cockcroft-Gault formula using the National
      Kidney Foundation classification system; Stage I (CrCl > or = 90); Stage II (60
      89); Stage III (30-59); Stage IV (15-29); and Stage V (< or = 15). The primary
      endpoint was the combined incidence of pseudoaneurysm, retroperitoneal hematoma,
      femoral artery thrombosis, surgical vascular repair, and groin infection.
      RESULTS: Among 610 patients 283 (46%) underwent PCI. The primary endpoint was
      seen in 66 (10.8%) patients. Univariate predictors of primary outcome were lower
      CrCl (p < 0.001), and presence of peripheral vascular disease (p = 0.03). There
      was an inverse relationship between CrCl and complication rate. CKD was the
      strongest independent multivariate predictor for the primary endpoint (OR 1.032;
      95% CI 1.019-1.046; p < 0.0001), driven by higher infection (p < 0.0001),
      thrombosis (p = 0.003) and hematoma (p = 0.007). CONCLUSIONS: Renal function
      appears to be significantly associated with vascular access-site complications.
      Worsening renal function is associated with higher vascular access site
      complications, largely driven by an increased infection rate.

PMID- 20048392
TI  - Making a smooth vascular exit--does your kidney function matter?

PMID- 20048393
TI  - Association between off-label use of drug-eluting stents and subsequent stent
      thrombosis: a case-control analysis.
AB  - OBJECTIVES: We sought to examine the association between off-label drug-eluting
      stent (DES) use and stent thrombosis (ST) in unselected patients undergoing
      percutaneous coronary intervention (PCI). BACKGROUND: DES are frequently used in
      clinical and angiographic scenarios not initially tested and approved by the FDA
      (off-label use) resulting in lingering concerns about the higher risk of ST in
      these situations. METHODS: Out of 5,383 patients undergoing PCI at a single
      center between 2004 and 2006, 380 had death or myocardial infarction within 1
      year. After adjudication using Academic Research Consortium definitions, patients
      with possible, probable or definite ST were termed cases. Cases were matched with
      controls, free of ST at 1 year, using geographic and temporal similarities. Off
      label usage was defined using manufacturer's instructions and other standard
      criteria. RESULTS: Overall, the proportion of off-label usage was higher among
      cases than controls (58% vs. 43%; p = 0.002) and both cases with
      definite/probable ST (77% vs. 59%; p = 0.08) and possible ST (54% vs. 37%; p =
      0.002) had a higher off-label use than respective controls. Off-label use among
      cases with ST remained higher within the following subgroups: off-label by
      manufacturer's criteria (36% vs. 27%; p = 0.05), left main stent implantation (2%
      vs. 0%; p = 0.01), ostial (12% vs. 6%; p = 0.04) and bifurcated lesions (26% vs.
      9%; p < 0.001). In multivariate analysis, being a case independently predicted
      off-label use (OR 1.68, 95% CI: 1.10-2.57; p = 0.02). CONCLUSIONS: In this case
      control analysis, off-label use of DES was independently associated with ST
      within 1 year, although the increased risk was moderate.

PMID- 20048394
TI  - Three years since the FDA advisory panel on drug-eluting stents: what have we
      learned about off-label use and stent thrombosis?

PMID- 20048395
TI  - How much alcohol should we infuse in the coronary artery of hypertrophic
      cardiomyopathy patients?
AB  - BACKGROUND: Although alcohol septal ablation (ASA) is increasingly used in
      hypertrophic cardiomyopathy (HC) patients who are refractory to medical therapy,
      the amount of alcohol that is required has not been well studied. This study
      sought to determine the amount of alcohol that is necessary to achieve clinical
      benefits of ASA. METHODS: Myocardial perfusion imaging was used to determine the
      size of the myocardial infarction produced by ASA in 54 HC patients. Left
      ventricular outflow gradients (LVOTg) were determined invasively before and after
      ASA and by Doppler echocardiography before and at a median of 3 months after ASA.
      RESULTS: LVOTg decreased at rest and after provocation in response to ASA and
      this was maintained on follow-up at 3 months. There was no relationship between
      the amount of alcohol infused and the infarct mass as determined by myocardial
      perfusion imaging. While the infarct mass was not correlated with the drop in the
      LVOTg at rest or with provocation, the quantity of alcohol infused was correlated
      with the drop in LVOTg at rest (r = 0.27, p = 0.05) and with provocation (r =
      0.34, p = 0.02). Furthermore, infusing more than 2ml of absolute alcohol was
      associated with a drop in the LVOTg by more than 60 mmHg at rest (p = 0.02) and
      by more than 130 mmHg with provocation (p = 0.05). CONCLUSIONS: Although lower
      amounts of alcohol infusion are desirable to avoid side-effects, it might be
      prudent to infuse around 2 ml of absolute alcohol in order to achieve the
      desirable degree of LVOTg reduction in ASA.

PMID- 20048396
TI  - Repeat coronary revascularization procedures after successful bare-metal or drug
      eluting stent implantation.
AB  - BACKGROUND: The goal of this study was to assess the rate and anatomical targets
      of repeat revascularization procedures in routine clinical practice after either
      bare-metal stent (BMS) or drug-eluting stent (DES) implantation. Randomized
      trials provide a reference standard for comparing outcomes after BMS or DES, but
      the rates of repeat revascularization procedures in clinical trials do not
      necessarily represent the rates in routine practice. METHODS: Baseline and 1-year
      follow-up angiographic data from a cardiac catheterization laboratory data
      registry with 31 participating hospitals were analyzed. RESULTS: In 17 hospitals
      14,459 eligible patients had a BMS implanted between 1998 and 2003, and in 20
      hospitals 9,575 eligible patients had a DES implanted in 2005. DES patients had
      more multivessel disease and diabetes than BMS patients, but fewer DES patients
      had all diseased vessels stented. Over the subsequent year, there were
      significantly fewer repeat procedures in the initially stented region after DES
      than BMS (4.7% vs. 8.1%), but significantly more procedures in previously
      unstented remote segments (7.8% vs. 4.3%). Consequently, the overall rate of
      additional percutaneous coronary intervention admissions was not reduced by DES
      (12.5% vs. 12.3%; p > 0.7). CONCLUSIONS: In this sample of routine clinical
      practice DES reduced repeat intervention of the stented segment to a lesser
      extent than has been reported in randomized trials. For our cohort, the reduction
      in restenosis was offset by increased use of additional interventional procedures
      to treat remote segments, predominantly within the first 2 months after initial
      stenting.

PMID- 20048397
TI  - Drug-eluting versus bare metal stents--a one horse race?

PMID- 20048398
TI  - A poly-N-acetyl glucosamine hemostatic dressing for femoral artery access site
      hemostasis after percutaneous coronary intervention: a pilot study.
AB  - BACKGROUND: Arterial puncture closure devices have improved time to hemostasis
      and ambulation after percutaneous coronary intervention (PCI) relative to
      traditional manual compression, though complication rates for both methods leave
      room for improvement. In a pilot registry, the authors evaluated a topical
      hemostatic dressing containing poly-N-acetyl glucosamine (p-GlcNAc) post PCI in
      fully anticoagulated patients. METHODS AND RESULTS: In 100 patients undergoing
      PCI via the common femoral artery in the short-stay unit, the p-GlcNAc hemostatic
      dressing was applied with 15 minutes of manual compression at arterial access
      sites after arterial sheath removal. Procedural antiplatelet and anticoagulation
      therapies were aspirin, clopidogrel and bivalirudin. Patients were observed
      during 2 hours of bed rest and attempted to ambulate 2 hours post hemostasis.
      Effectiveness was assessed based on times to hemostasis and ambulation. Data were
      stratified by time elapsed since bivalirudin bolus or discontinuation of infusion
      (30 minutes, > 30-60 minutes, > 60 minutes). Mean time to hemostasis was 15.5
      minutes. Mean time from hemostasis to ambulation was 2.08 hours; 87% of patients
      ambulated at 2 hours. Sheaths were removed at a mean 40.38 minutes after
      discontinuing bivalirudin. Anticoagulation status (as assessed by time since
      discontinuation of bivalirudin) did not influence time to hemostasis or
      ambulation. There was a single major complication (pseudoaneurysm), two minor
      rebleeds requiring additional manual compression, and 1 hematoma > 5 cm.
      CONCLUSIONS: This p-GlcNAc topical hemostatic dressing safely achieved hemostasis
      at arterial access sites and early ambulation, even with nearly immediate sheath
      removal after PCI with systemic anticoagulation using bivalirudin.

PMID- 20048399
TI  - Unresolved issues associated with early initiation of antiplatelet therapy in
      acute coronary syndromes.
AB  - Early initiation of antiplatelet therapy in addition to aspirin is critical for
      all patients with acute coronary syndrome (ACS) due to improved short- and long
      term outcomes. Thus, evidence-based practice guidelines for ACS management
      recommend early and intensive initiation of antiplatelet therapy with aspirin,
      clopidogrel, and/or glycoprotein (GP) IIb/IIIa inhibitors. Despite the
      comprehensive nature of current guidelines, several important clinical issues
      concerning the optimal initiation of antiplatelet therapy remain. This review
      addresses four of these clinical issues: When should GP IIb/IIIa inhibitors be
      initiated? When should clopidogrel be initiated? What is the optimal clopidogrel
      loading dose? How should antiplatelet therapy be approached in chronically
      anticoagulated patients?

PMID- 20048400
TI  - Unusual coronary anatomical anomaly: common origin for all three major coronary
      arteries arising from the right coronary sinus.

PMID- 20048401
TI  - Complete atrioventricular block: a rare presentation of mitral valve
      endocarditis.
AB  - Infective endocarditis is one of the uncommon causes of complete atrioventricular
      (AV) block. Complications from aortic valve infection are more often associated
      with conduction abnormalities than with mitral valve endocarditis. In fact,
      complete AV block rarely occurs in mitral valve infections, with only a few cases
      having been reported. We report a case of mitral valve endocarditis in which the
      initial presentation was fever and newly developed, complete AV block. Patients
      with mitral valve endocarditis complicated by complete AV block are at high risk.
      Prompt investigation, administration of appropriate antibiotics and consideration
      of early surgical intervention are needed.

PMID- 20048402
TI  - Inability of intracoronary stenting to provide long-term relief for coronary
      compression secondary to chronic constrictive pericarditis.
AB  - Chronic constrictive pericarditis can result in extrinsic compression of coronary
      arteries during diastole. We present one such case wherein the coronary
      compression and the resultant cardiac ischemia developed late after surgical
      pericardiectomy, and treatment with intracoronary stenting was unsuccessful.
      Issues pertaining to management of this rare condition are discussed and a case
      made for surgical treatment for such patients.

PMID- 20048403
TI  - Successful retrograde recanalization of a left anterior descending artery chronic
      total occlusion through a previously placed left anterior descending-to-diagonal
      artery stent.
AB  - Since the introduction of the retrograde technique, the success rate of chronic
      total occlusion (CTO) percutaneous coronary intervention (PCI) has increased
      significantly in patients with suitable anatomy. To our knowledge, retrograde
      recanalization of a CTO from the abluminal side of a previously placed stent has
      not been reported. We describe a case of retrograde PCI of a mid left anterior
      descending (LAD) artery CTO through a previously placed proximal LAD stent which
      extended into the diagonal artery. The occluded mid LAD was recanalized using the
      retrograde approach in which retrograde wire crossing into the proximal LAD was
      successful only after high pressure balloon expansion of the previously placed
      proximal LAD-to-diagonal stent. Intravascular ultrasound imaging was also used to
      confirm an intraluminal location of the retrograde guidewire.

PMID- 20048404
TI  - Don't rule out retroperitoneal bleeding just because the angiogram was done from
      the radial artery.
AB  - The use of radial artery for vascular access for cardiac catheterization and
      intervention has gained increasing acceptance over the last few years as result
      of the lower risk of vascular complications compared to use of the femoral
      artery. The strong evidence showing that major bleeding (commonly access site
      related) is an independent predictor of mortality in acute coronary syndrome
      patients undergoing intervention has only accelerated this change. This case
      highlights that although the risk of access site complications is reduced with
      the radial approach there remains a risk of spontaneous bleeding elsewhere due to
      the use of multiple potent antiplatelet and anticoagulant therapy in the
      treatment of acute coronary syndromes. Early recognition of bleeding is of the
      utmost importance as delay increases the likelihood complications of bleeding
      including death.

PMID- 20048405
TI  - Spontaneous multivessel coronary artery dissection.
AB  - As opposed to iatrogenic coronary dissection, spontaneous dissection is an
      extremely rare clinical condition. Typically seen in a single coronary vessel of
      peripartum women presenting with acute coronary syndrome, there are isolated case
      reports of men presenting multivessel involvement for this life-threatening
      condition. We describe a 54-year-old male with a history of diabetes,
      hypertension and methamphetamine abuse who presented to the emergency after a
      brief, witnessed cardiac arrest. Admission ECG revealed sinus tachycardia with
      inferior Q waves. He was found to have frequent runs of non-sustained ventricular
      tachycardia and minimal troponin-T elevation. His 2-D echocardiogram showed
      apical akinesis with an ejection fraction of 50%. Cardiac catheterization
      revealed a patent left main artery with a spontaneous dissection involving the
      mid to distal LAD artery, as well as large first diagonal branch with proximal
      dissection. His dominant RCA also showed long spontaneous dissection extending
      from proximal to distal vessel, along with distal focal 90% atherosclerotic
      lesion. Ramus intermedius and left circumflex vessels were free of disease. The
      patient underwent a 2-vessel coronary artery bypass grafting (CABG) with
      excellent outcome. Although cocaine abuse has been known to be associated with
      spontaneous dissection, this is the first reported case of a methamphetamine user
      presenting with multivessel coronary dissection.

PMID- 20048406
TI  - Retrograde recanalization of a chronic ostial occlusion of the left anterior
      descending artery: how to manage extreme takeoff angles.
AB  - Chronic total coronary occlusions (CTO) still remain one of the most technically
      challenging clinical scenearios in which to perform interventions. Although the
      antegrade approach is the most common method of CTO recanalization, a retrograde
      attempt improves the success rate and its usagehas been increasingly adopted in
      the recent years. However, the retrograde method requires exceptional expertise
      and skills in order to apply a wide variety of strategies, devices and imaging
      modalities. We report a case of retrograde recanalization of an ostial left
      anterior descending artery CTO of at least 10 years duration, and discuss some
      specific issues of a new channel dilating catheter, and practical precautions to
      keep in mind in the retrograde approach such as the availability of snare
      technique to facilitate retrograde wire capture and externalization.

PMID- 20048408
TI  - CdZn2KB2O6F, a new fluoride borate crystal.
AB  - During an attempt to grow crystals of the nonlinear optical material
      Cd(3)Zn(3)B(4)O(12) using a KBF(4) flux, crystals of a new cadmium dizinc
      potassium borate fluoride compound, CdZn(2)KB(2)O(6)F, were unexpectedly
      isolated. The structure consists of layers constructed of distorted corner
      sharing ZnO(3)F tetrahedra and BO(3) triangles. Both Zn and B reside on threefold
      rotation axes, while the F(-) anion is located at a site of 3.2 symmetry. The
      Cd(II) (site symmetry 3) and K(+) (site symmetry 3.2) ions occupy six- and nine
      coordinate interlayer sites, respectively. The BO(3) triangles and ZnO(3)
      pyramids from the ZnO(3)F tetrahedra share bridging O atoms with each other to
      form an extended [ZnBO(3)] layer parallel to (001). Although these layers are
      similar to the [MBO(3)] layers seen in other compounds, they are uniquely bridged
      here by the Cd centres and F(-) anions to form a three-dimensional framework. In
      so doing, a series of channels is formed along the [010] direction and the K(+)
      cations are found in these channels.

PMID- 20048409
TI  - [Not Available].
AB  - The title compound, namely lithium cobalt(II/III) bis(diphosphate),
      Li(4.03)Co(1.97)(P(2)O(7))(2), is a new mixed-valent lithium/cobalt(II/III)
      phosphate. Three metal sites out of seven are occupied simultaneously by Li(+)
      and Co(II/III) ions. This disorder was established both from an analysis of the
      atomic displacement ellipsoids and Li/Co-O bond distances, and by means of a
      charge-distribution (CHARDI) model, which provides satisfactory agreement on the
      computed charges (Q) for all the cations.

PMID- 20048410
TI  - KBa7Mg2B14O28F5, a new borate with an unusual heptaborate group and double
      perovskite unit.
AB  - A new borate, potassium barium magnesium borate fluoride,
      KBa(7)Mg(2)B(14)O(28)F(5), with a nominal 7:1 composition of BaB(2)O(4) to
      KMg(2)F(5), has been found during the growth of BaMgBO(3)F crystals with a KF
      flux. It crystallized in the space group C2/c and is composed of isolated
      heptaborate [B(7)O(14)](7-) groups and double perovskite [Mg(2)O(6)F(5)](13-)
      units.

PMID- 20048411
TI  - Intermolecular dihydrogen- and hydrogen-bonding interactions in diammonium closo
      decahydrodecaborate sesquihydrate.
AB  - The asymmetric unit of the title salt, 2NH(4)(+).B(10)H(10)(2-).1.5H(2)O or
      (NH(4))(2)B(10)H(10).1.5H(2)O, (I), contains two B(10)H(10)(2-) anions, four
      NH(4)(+) cations and three water molecules. (I) was converted to the anhydrous
      compound (NH(4))(2)B(10)H(10), (II), by heating to 343 K and its X-ray powder
      pattern was obtained. The extended structure of (I) shows two types of hydrogen
      bonding interactions (N-H...O and O-H...O) and two types of dihydrogen-bonding
      interactions (N-H...H-B and O-H...H-B). The N-H...H-B dihydrogen bonding forms a
      two-dimensional sheet structure, and hydrogen bonding (N-H...O and O-H...O) and O
      H...H-B dihydrogen bonding link the respective sheets to form a three-dimensional
      polymeric network structure. Compound (II) has been shown to form a polymer with
      the accompanying loss of H(2) at a faster rate than (NH(4))(2)B(12)H(12) and we
      believe that this is due to the stronger dihydrogen-bonding interactions shown in
      the hydrate (I).

PMID- 20048412
TI  - Zoledronate complexes. I. Poly[[mu2-aqua[mu3-1-hydroxy-2-(1H,3H-imidazol-3-ium-1
      yl)ethylidenediphosphonato]potassium(I)] monohydrate].
AB  - The title compound, {[K(C(5)H(9)N(2)O(7)P(2))(H(2)O)].H(2)O}(n), is polymeric and
      consists of layers parallel to (001) interconnected by hydrogen-bonding and pi-pi
      interactions. The K(+) cation is eightfold coordinated in a KO(8) environment by
      O atoms from three different chelating zoledronate units and two coordinated
      water molecules. The zoledronate group presents its usual zwitterionic character,
      with negative charges in the singly protonated phosphonate groups and a positive
      charge at the protonated imidazole N atom. The anion binds to three different
      K(+) cations in a (so far unreported) triply chelating manner. Intra- and
      interplanar interactions are enhanced by a variety of hydrogen bonds involving
      all available O-H and N-H donors. A strong imidazole-phosphonate C-H...O
      interaction is present in the structure.

PMID- 20048413
TI  - The hydrated and anhydrous gold(III) tetrachloride salts of L-ecgonine, an
      important forensic toxicology marker for cocaine.
AB  - The structure of the hydrated gold(III) tetrachloride salt of L-ecgonine
      {hydronium tetrakis[(1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8
      azoniabicyclo[3.2.1]octane-2-carboxylate pentakis[tetrachloridoaurate(III)]
      hexahydrate}, (C(9)H(16)NO(3))(4)(H(3)O)[AuCl(4)](5).6H(2)O, demonstrates an
      unprecedented stoichiometric relationship between the cations and anions in the
      unit cell. The previous tropane alkaloid structures, including the related
      hydrochloride salts, all have a cation-anion ratio of 1:1, as does the anhydrous
      salt described here, namely (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8
      azoniabicyclo[3.2.1]octane-2-carboxylate tetrachloridoaurate(III),
      (C(9)H(16)NO(3))[AuCl(4)]. The hydrated salt, however, consists of four
      monopositive N-protonated units of the alkaloid and five [AuCl(4)](-) counter
      ions, plus seven solvent water molecules. The H atom required for change balance
      has been assigned to a water molecule. In addition, the hydrate has a novel
      arrangement, with all seven of the water molecules and all of the O atoms in the
      cations participating in an alternating arrangement of interleaved sheets of the
      anionic species. Both the hydrate and the anhydrous salt of the same
      toxicologically important marker for cocaine show that the cation and anion are
      in close proximity to each other, as was found in the gold(III) tetrachloride
      salt of L-cocaine.

PMID- 20048414
TI  - catena-Poly[[bis(acetonitrile-kappaN)manganese(II)]-bis(mu
      trifluoromethanesulfonato-kappa2O:O')].
AB  - The title compound, [Mn(CF(3)SO(3))(2)(CH(3)CN)(2)](n), has an Mn(II) cation on
      an inversion centre in an octahedral environment. The trifluoromethanesulfonate
      anions act as bridging ligands and form a one-dimensional coordination polymer in
      the direction of the a axis. The F atoms of the trifluoromethanesulfonate anions
      form layers parallel to the ab plane, but despite short intermolecular distances,
      no stabilizing F...F interactions are detected. The Mn-N and C-C bonds of the
      acetonitrile ligand are analyzed according to the Hirshfeld rigid-bond test.
      Renninger effects in the reflection data are considered, explored and discussed.

PMID- 20048415
TI  - 7-Methoxy-2,3-dioxo-1,4-dihydroquinoxalin-6-aminium chloride monohydrate.
AB  - Single crystals of the title compound, C(9)H(10)N(3)O(3)(+).Cl(-).H(2)O, were
      obtained by recrystallization from hydrochloric acid. The cations stack along the
      crystallographic a direction. The 2,3-dioxo-1,4-dihydroquinoxaline group shows a
      significant deviation from planarity [r.m.s. deviation from the best plane =
      0.063 (2) A]. Hydrogen bonding links the cations, chloride anions and water
      molecules to form an extended three-dimensional architecture.

PMID- 20048416
TI  - (E)-4,4'-Bis(1,3-benzoxazol-2-yl)stilbene at 150 and 375 K.
AB  - The title compound, a chromophore of formula C(28)H(18)N(2)O(2), crystallizes
      with the molecule lying on an inversion centre to give one-half of a
      crystallographically independent molecule in the asymmetric unit. The molecule is
      almost planar, with slight deviation of the benzene rings from the mean molecular
      plane. The structure is characterized by a herringbone packing arrangement
      arising from C-H...pi and pi-pi intermolecular interactions. The benzoxazole
      group is disordered between two orientations, with occupancy factors of 0.669
      (10) and 0.331 (10) at 150 K [0.712 (7) and 0.288 (7) at 375 K].

PMID- 20048417
TI  - Dithioether ligands containing a 2,6-disubstituted pyridine linker with two
      thioether-heterocycle arms.
AB  - The structure of 2,6-bis(2-pyridyltsulfanylmethyl)pyridine (pytmp), (I),
      C(17)H(15)N(3)S(2), presents a twisted conformation, with the three planar
      moieties almost perpendicular to each other. The structures of two related
      derivatives, namely 2,6-bis(6-methyl-2-pyridylsulfanylmethyl)pyridine (mpytmp),
      (II), C(19)H(19)N(3)S(2), and 2,6-bis(4-methyl-2-pyrimidylsulfanylmethyl)pyridine
      (mprtmp) n-pentane hemisolvate, (III), C(17)H(17)N(5)S(2).0.5C(5)H(12), present
      extended planar fragments with just one quasi-perpendicular arylsulfanylmethyl
      side arm, such that the molecules are folded in an L-shaped conformation. All
      three conformations appear different from those adopted by similar compounds,
      demonstrating the great flexibility of such species, although such differences in
      conformational behaviour might drive specific coordination modes.

PMID- 20048418
TI  - A pair of diastereomeric 1:2 salts of (R)- and (S)-2-methylpiperazine with
      (2S,3S)-tartaric acid.
AB  - The crystal structures of a pair of diastereomeric 1:2 salts of (R)- and (S)-2
      methylpiperazine with (2S,3S)-tartaric acid, namely (R)-2-methylpiperazinediium
      bis[hydrogen (2S,3S)-tartrate] monohydrate, (I), and (S)-2-methylpiperazinediium
      bis[hydrogen (2S,3S)-tartrate] monohydrate, (II), both
      C(5)H(14)N(2)(2+).2C(4)H(5)O(6)(-).H(2)O, each reveal the formation of well
      defined head-to-tail-connected hydrogen tartrate chains; these chains are linked
      into a two-dimensional sheet via intermolecular hydrogen bonds involving hydroxy
      groups and water molecules, resulting in a layer structure. The (R)-2
      methylpiperazinediium ions lie between the hydrogen tartrate layers in the most
      stable equatorial conformation in (I), whereas in (II), these ions are in an
      unstable axial position inside the more interconnected layers and form a larger
      number of intermolecular hydrogen bonds than are observed in (I).

PMID- 20048419
TI  - A simple hydrogen-bonded chain in (3Z)-3-{1-[(5-phenyl-1H-pyrazol-3
      yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one, and a hydrogen-bonded ribbon of
      centrosymmetric rings in the self-assembled adduct (3Z)-3-{1-[(5-methyl-1H
      pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one-6-(2-hydroxyethyl)-2,5
      dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one (1/1).
AB  - (3Z)-3-{1-[(5-Phenyl-1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)
      one, C(15)H(15)N(3)O(2), (I), and the stoichiometric adduct (3Z)-3-{1-[(5-methyl
      1H-pyrazol-3-yl)amino]ethylidene}-4,5-dihydrofuran-2(3H)-one-6-(2-hydroxyethyl)
      2,5-dimethylpyrazolo[1,5-a]pyrimidin-7(4H)-one (1/1),
      C(10)H(13)N(3)O(2).C(10)H(13)N(3)O(2), (II), in which the two components have the
      same composition but different constitutions, are formed in the reactions of 2
      acetyl-4-butyrolactone with 5-amino-3-phenyl-1H-pyrazole and 5-amino-3-methyl-1H
      pyrazole, respectively. In each compound, the furanone component contains an
      intramolecular N-H...O hydrogen bond. The molecules of (I) are linked into a
      chain by a single intermolecular N-H...O hydrogen bond, while in (II), a
      combination of one O-H...N hydrogen bond, within the selected asymmetric unit,
      and two N-H...O hydrogen bonds link the molecular components into a ribbon
      containing alternating centrosymmetric R(4)(4)(20) and R(6)(6)(22) rings.

PMID- 20048420
TI  - Monitoring structural transformations in crystals. 13. On photocyclization in
      2,3,4,5,6-pentamethylbenzophenone, 1,3-diphenylbutan-1-one and 2,4,6-triisopropyl
      4'-methoxybenzophenone.
AB  - The geometrical parameters governing the potential for the photocyclization
      reaction occurring in crystals of 2,3,4,5,6-pentamethylbenzophenone, C(18)H(20)O,
      (I), 1,3-diphenylbutan-1-one, C(16)H(16)O, (II), and 2,4,6-triisopropyl-4'
      methoxybenzophenone, C(23)H(30)O(2), (IV), have been evaluated. Compound (IV)
      undergoes photocyclization but (I) and (II) do not, despite the fact that their
      geometrical parameters appear equally favourable for reaction. The structure of
      the partially reacted crystal of the photoactive compound, i.e. 2,4,6
      triisopropyl-4'-methoxybenzophenone-3,5-diisopropyl-7-(4-methoxyphenyl)-8,8
      dimethylbicyclo[4.2.0]octa-1,3,5-trien-7-ol (9/1),
      0.90C(23)H(30)O(2).0.10C(23)H(30)O(2), (III), was also determined, providing
      structural evidence for the reactivity of the compound. It has been found that
      the carbonyl group of the photoactive compound reacts with one of the two o
      isopropyl groups. The study has shown that the intramolecular geometrical
      parameters are not the only factors influencing the reactivity of compounds in
      crystals.

PMID- 20048421
TI  - Multicomponent crystals of erlotinib.
AB  - Erlotinib [systematic name: N-(3-ethynylphenyl)-6,7-bis(2
      methoxyethoxy)quinazolin-4-amine], a small-molecule epidermal growth factor
      receptor inhibitor, useful for the treatment of non-small-cell lung cancer, has
      been crystallized as erlotinib monohydrate, C(22)H(23)N(3)O(4).H(2)O, (I), the
      erlotinib hemioxalate salt [systematic name: 4-amino-N-(3-ethynylphenyl)-6,7
      bis(2-methoxyethoxy)quinazolin-1-ium hemioxalate],
      C(22)H(24)N(3)O(4)(+).0.5C(2)O(4)(2-), (II), and the cocrystal erlotinib fumaric
      acid hemisolvate dihydrate, C(22)H(23)N(3)O(4).0.5C(4)H(4)O(4).2H(2)O, (III). In
      (II) and (III), the oxalate anion and the fumaric acid molecule are located
      across inversion centres. The water molecules in (I) and (III) play an active
      role in hydrogen-bonding interactions which lead to the formation of tetrameric
      and hexameric hydrogen-bonded networks, while in (II) the cations and anions form
      a tetrameric hydrogen-bonded network in the crystal packing. The title
      multicomponent crystals of erlotinib have been elucidated to study the assembly
      of molecules through intermolecular interactions, such as hydrogen bonds and
      aromatic pi-pi stacking.

PMID- 20048422
TI  - 2-Cyano-N-(2,6-dimethoxypyrimidin-4-yl)-3-[4-(dimethylamino)phenyl]acrylamide and
      dimethylammonium 6-cyano-1,3-dimethyl-2,4,5-trioxo-1,2,3,4,5,8
      hexahydropyrido[2,3-d]pyrimidin-8-ide: a pi-stacked dimer and a hydrogen-bonded
      ribbon containing three types of ring.
AB  - The bond distances in 2-cyano-N-(2,6-dimethoxypyrimidin-4-yl)-3-[4
      (dimethylamino)phenyl]acrylamide, C(18)H(19)N(5)O(3), (I), and in the anionic
      component of the salt dimethylammonium 6-cyano-1,3-dimethyl-2,4,5-trioxo
      1,2,3,4,5,8-hexahydropyrido[2,3-d]pyrimidin-8-ide,
      C(2)H(8)N(2)(+).C(10)H(7)N(4)O(3)(-), (II), provide evidence for the occurrence
      of electronic polarization. There are no hydrogen bonds in the structure of (I),
      instead pairs of molecules are linked into centrosymmetric dimers by a single pi
      pi stacking interaction. In (II), a combination of a two-centre N-H...O hydrogen
      bond, a three-centre N-H...(O)(2) hydrogen bond, together utilizing all three O
      atoms, and a two-centre C-H...N hydrogen bond, link the components into a ribbon
      containing R(1)(2)(6), R(2)(2)(10) and R(6)(6)(30) rings.

PMID- 20048423
TI  - 1-(6-Amino-1,3-benzodioxol-5-yl)-3-(2-oxo-1,2-dihydroquinolin-3-yl)prop-2-enone:
      a sheet built by pi-stacking of hydrogen-bonded chains of rings.
AB  - The bond distances in the molecule of the title compound, C(19)H(14)N(2)O(4),
      provide evidence for electronic polarization in the aminoarylpropenone fragment
      and for bond fixation in the quinolinone unit. Molecules are linked by N-H...O
      and C-H...O hydrogen bonds into chains in which centrosymmetric rings of
      R(2)(2)(8) and R(2)(2)(18) types alternate, and these chains are linked into
      sheets by a single aromatic pi-pi stacking interaction.

PMID- 20048424
TI  - 5-Amino-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde hemihydrate: a polarized
      electronic structure within hydrogen-bonded sheets of R(10)(8)(34) rings.
AB  - In the title compound, C(11)H(11)N(3)O.0.5H(2)O, the water molecule lies across a
      twofold rotation axis in the space group Pbcn. The bond distances in the organic
      component provide evidence for polarization of the electronic structure. The
      molecular components are linked into puckered sheets of R(10)(8)(34) rings by a
      combination of O-H...N and N-H...O hydrogen bonds; adjacent sheets are weakly
      linked by an aromatic pi-pi stacking interaction. Comparisons are made with some
      fused-ring analogues.

PMID- 20048425
TI  - Three-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds
      of L-tartaric acid with the associative-group monosubstituted pyridines 3
      aminopyridine, 3-carboxypyridine (nicotinic acid) and 2-carboxypyridine
      (picolinic acid).
AB  - The 1:1 proton-transfer compounds of L-tartaric acid with 3-aminopyridine [3
      aminopyridinium hydrogen (2R,3R)-tartrate dihydrate,
      C(5)H(7)N(2)(+).C(4)H(5)O(6)(-).2H(2)O, (I)], pyridine-3-carboxylic acid
      (nicotinic acid) [anhydrous 3-carboxypyridinium hydrogen (2R,3R)-tartrate,
      C(6)H(6)NO(2)(+).C(4)H(5)O(6)(-), (II)] and pyridine-2-carboxylic acid [2
      carboxypyridinium hydrogen (2R,3R)-tartrate monohydrate,
      C(6)H(6)NO(2)(+).C(4)H(5)O(6)(-).H(2)O, (III)] have been determined. In (I) and
      (II), there is a direct pyridinium-carboxyl N(+)-H...O hydrogen-bonding
      interaction, four-centred in (II), giving conjoint cyclic R(1)(2)(5)
      associations. In contrast, the N-H...O association in (III) is with a water O
      atom acceptor, which provides links to separate tartrate anions through
      O(hydroxy) acceptors. All three compounds have the head-to-tail C(7) hydrogen
      bonded chain substructures commonly associated with 1:1 proton-transfer hydrogen
      tartrate salts. These chains are extended into two-dimensional sheets which, in
      hydrates (I) and (III) additionally involve the solvent water molecules. Three
      dimensional hydrogen-bonded structures are generated via crosslinking through the
      associative functional groups of the substituted pyridinium cations. In the sheet
      structure of (I), both water molecules act as donors and acceptors in
      interactions with separate carboxyl and hydroxy O-atom acceptors of the primary
      tartrate chains, closing conjoint cyclic R(4)(4)(8), R(3)(4)(11) and R(3)(3)(12)
      associations. Also, in (II) and (III) there are strong cation carboxyl-carboxyl O
      H...O hydrogen bonds [O...O = 2.5387 (17) A in (II) and 2.441 (3) A in (III)],
      which in (II) form part of a cyclic R(2)(2)(6) inter-sheet association. This
      series of heteroaromatic Lewis base-hydrogen L-tartrate salts provides further
      examples of molecular assembly facilitated by the presence of the classical two
      dimensional hydrogen-bonded hydrogen tartrate or hydrogen tartrate-water sheet
      substructures which are expanded into three-dimensional frameworks via peripheral
      cation bifunctional substituent-group crosslinking interactions.

PMID- 20048426
TI  - Synthesis and structures of substituted triphenyl(phenylimino)phosphoranes.
AB  - Three substituted triphenyl(phenylimino)phosphoranes, namely (4
      cyanophenylimino)triphenylphosphorane, C(25)H(19)N(2)P, (I), (4
      nitrophenylimino)triphenylphosphorane, C(24)H(19)N(2)O(2)P, (II), and (3
      nitrophenylimino)triphenylphosphorane, C(24)H(19)N(2)O(2)P, (III), were
      synthesized as precursors for the preparation of substituted
      diphenylcarbodiimides. All three compounds display a supramolecular arrangement
      in which the substituted benzene rings are organized in an antiparallel fashion.
      The nitro group on the ring participates in C-H...O and O...pi interactions,
      forming intermolecular dimers. Compound (III) shows disorder which involves the
      rotation of one of the phenyl rings of the triphenylphosphine group.

PMID- 20048427
TI  - Hydrogen-bond motifs in N-monosubstituted derivatives of barbituric acid: 5-allyl
      5-isopropyl-1-methylbarbituric acid (enallylpropymal) and 1,5-di(but-2-enyl)-5
      ethylbarbituric acid.
AB  - Both title structures exhibit essentially planar barbiturate rings. The crystal
      structure of enallylpropymal (5-allyl-5-isopropyl-1-methylbarbituric acid),
      C(11)H(16)N(2)O(3), is composed of centrosymmetric N-H...O hydrogen-bonded
      dimers, while 1,5-di(but-2-enyl)-5-ethylbarbituric acid, C(14)H(20)N(2)O(3),
      forms N-H...O hydrogen-bonded helical chains. Each of the ten known crystal
      structures of closely related N-monosubstituted derivatives of barbituric acid
      displays one of the fundamental N-H...O hydrogen-bonded motifs of the two title
      structures, i.e. either a dimer or a chain.

PMID- 20048428
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium channel blockers and EBM].
AB  - Calcium channel blockers are antihypertensive drugs which are prescribed widely
      for reducing high blood pressures. This is due to confirmed and stable efficacy,
      small side effects, and less influence on metabolism. Nowadays, many clinical
      trials, studies have proven that calcium channel blockers strongly reduce high
      blood pressure, prevent cardiovascular disease and stroke, and regress left
      ventricular hypertrophy. Some studies suggest that they are as beneficial as ACE
      inhibitors, angiotensin II receptor blockers, and diuretics.

PMID- 20048429
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium channel blockers and JSH2009].
AB  - Japanese Society of Hypertension Committee published Guidelines for the
      Management of Hypertension in 2009 (JSH2009). The first choices of
      antihypertensive drugs are calcium channel blockers, angiotensin II receptor
      blockers, angiotensin converting enzyme inhibitors, diuretics, and beta
      adrenergic blockers. Because dihydropyridine calcium channel blockers have the
      greatest hypotensive efficacy without affecting organ blood flow, they are
      indicated in the patients with complications and the aged. Positive indications
      of calcium channel blockers are left ventricular hypertrophy, tachycardia (non
      dihydropyridine), angina pectoris, chronic phase of cerebrovascular disease, and
      elderly patients. Patients with bradycardia are contraindicated by non
      dihydropyridine calcium channel blockers.

PMID- 20048430
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Classification of calcium channel blockers].
AB  - Calcium channel blockers have been widely recognized as important medicines for
      the treatment of cardiovascular diseases, including hypertension and angina
      pectoris. In Japan, more than 15 calcium channel blockers are clinically
      available, and their pharmacological profiles are known to vary in terms of
      action on subtypes of voltage-dependent Ca(2+) channels, tissue selectivity, and
      influence on the sympathetic nerve activity. Thus, the classification of calcium
      channel blockers is useful for understanding the similarity and differences of
      the drugs' action, leading to optimum prescription.

PMID- 20048431
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium channel blockers and autonomic nervous system].
AB  - Calcium channel blockers are widely used for the treatment of hypertension.
      Although they are effective for their strong vasodilator action, there are
      concerns regarding related baroreflex-mediated activation of sympathetic nervous
      system. However, long-acting calcium channel blockers, such as amlodipine, are
      now known safe for the treatment of hypertension. Furthermore, the new type of
      calcium channel blockers, such as cilnidipine with N-type calcium channel
      blocking action, or azelnidipine that has sympatho-inhibitory action with anti
      oxidant effect, provide a new insight for the future use of calcium channel
      blockers.

PMID- 20048432
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Effects of calcium channel blockers on oxidative stress].
AB  - Calcium channel blockers (CCB) are widely used for the treatment of hypertension
      and angina pectoris. In vitro experiments show that CCBs decrease oxidative
      stress via multiple pathways. In various animal models, protective effects of
      CCBs against oxidative stress and organ injury have been examined. The data
      obtained indicate that organ-protective effects of CCBs, which cannot be simply
      explained by their hypotensive action, are largely mediated through their strong
      antioxidative effects. Clinical studies also support the idea that CCBs may be
      effective in reducing organ injury associated with oxidative stress during the
      development of hypertension. In this review, we discuss the potential mechanisms
      mediating the CCB-dependent antioxidative effects.

PMID- 20048433
TI  - [Calcium antagonists: current and future applications based on new evidence. The
      mechanisms on lowering serum uric acid level by calcium channel blockers].
AB  - In hypertensive subjects, their serum uric acid levels tend to be higher because
      of decreasing urinary secretion or overproduction of uric acid. Among calcium
      channel blockers (CCBs) , long acting nifedipine and cilnidipine reveal serum
      uric acid lowering action. They decrease the production of uric acid precursor in
      skeletal muscles under anaerobic condition induced by hypertension or insulin
      resistance. Hyperuricemia is considered to be a risk factor of not only gout but
      also renal and cardiovascular diseases, thus, it is important to use CCBs without
      adverse effect on uric acid metabolisms.

PMID- 20048434
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Combination antihypertensive therapy with calcium channel blockers].
AB  - Because epidemiological studies have indicated that the relation of blood
      pressure to cardiovascular risk is lineally extended to the normal blood pressure
      range, strict blood pressure control is desired in the antihypertensive therapy.
      For this purpose, combination of multiple antihypertensive drug is required in a
      large part of hypertensive patients. In combining antihypertensive drugs, it is
      preferable that the antihypertensive effects are augmented and the adverse
      effects are cancelled each other. Calcium channel blockers exert consistent
      hypotensive effects dose-dependently and scarcely cause hazardous side effects.
      Calcium channel blockers are preferentially used when angina pectoris and
      cerebrovascular disease exist, moreover, the prominent antihypertensive effects
      are useful as combination drugs for the treatment of diabetes mellitus and
      chronic renal diseases where the strict blood pressure control is strongly
      needed.

PMID- 20048435
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium channel blockers and single-pill combination].
AB  - Ca channel blocker (CCB) is widely used as an anti-hypertensive and anti-ischemic
      heart disease drug in Japan. CCB or angiotensin receptor antagonist (ARB) is
      selected as a first line anti-hypertensive drug. However, mono-therapy is often
      insufficient and combination therapy is needed to achieve the adequate blood
      pressure control. Hypertensive patients are also sometimes combined with
      dyslipidemia. In these reasons, a single pill combination of CCB and ARB or
      statin play an important role in hypertensive and anti-atherosclerotic therapy.

PMID- 20048436
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Pleiotropic effects of calcium channel blockers on vascular endothelial
      function].
AB  - Ample evidence has demonstrated that calcium channel blockers (CCBs) exert
      pleiotropic effects on vasculature, leading to restoring endothelial dysfunction
      and suppressing progression of atherosclerosis both in experimental and clinical
      settings. CCBs protect vasculature by various antioxidative mechanisms as follows
      : stimulating endothelial NO production and/or restoring decline in circulating
      adiponectin and HDL level. Moreover, CCBs has been also demonstrated to enhance
      circulating endothelial progenitor cell level, of which has been known to
      correlate to endothelial function. through its antioxidative property.
      Accordingly, these evidences suggest that CCB could be expected as another
      antiatherosclerotic remedy in patient population.

PMID- 20048437
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium antagonists and diabetes].
AB  - Diabetic vascular complication is a leading cause of acquired blindness, end
      stage renal failure, a variety of neuropathies and accelerated atherosclerosis,
      which could account for disabilities and high mortality rates in patients with
      diabetes. The formation and accumulation of advanced glycation end products
      (AGEs) have been known to progress at an accelerated rate in diabetes. Recent
      understanding of this process has confirmed that AGEs-their receptor RAGE system
      is implicated in the pathogenesis of diabetic vascular complication. Therefore,
      besides blood glucose and pressure control, the inhibition of the AGE-RAGE axis
      may be a novel therapeutic target for preventing vascular complications in
      diabetes. Recently, nifedipine, one of the most widely used Ca channel blockers,
      has been reported to exert anti-oxidative and anti-AGE-RAGE axis properties. The
      use of nifedipine, in addition to ensuring blood pressure control, may have
      beneficial effects in preventing cardiorenal vascular events in patients with
      diabetes.

PMID- 20048438
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Neuroprotective effect of calcium antagonists].
AB  - Voltage-dependent Ca(2+) channels have been divided into at least 5 types (L-, N
      , T-, P-, and Q-type). L/N-type Ca(2+) channel blocker cilnidipine could reduce
      the size of cerebral infarction in the rat focal brain ischemia. L-type Ca(2+)
      channel blocker amlodipine reduced cerebral edema and inhibit neuronal cell
      death. N-type Ca(2+) channel blocker omega-conotoxin reduce the size of cerebral
      infarction and inhibit delayed neuronal cell death in hippocampal CA1 area. It is
      suggested that calcium antagonist has neuroprotective effect.

PMID- 20048439
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Cardio-protective effect of calcium antagonists].
AB  - Calcium antagonists block calcium influx through the L-type calcium channel to
      produce dilatation of resistant arteries including coronary arteries. Due to
      arterial vasodilatation, calcium antagonists have beneficial effects for ischemic
      heart disease, left ventricular hypertrophy and heart failure. Some of calcium
      antagonists are known to have the inhibitory action for T-type or N-type calcium
      channel which might be beneficial for the inhibition of reactive tachycardia.
      Calcium antagonists may also retard the progression of atherosclerosis to prevent
      cardiovascular events.

PMID- 20048440
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Renal protective action of calcium channel blockers].
AB  - Ca channel blockers have been widely prescribed as an antihypertensive agent in
      Japan, because the blood pressure (BP) lowering effect of it is strong among
      Japanese patients whose amount of salt intake is high and patients with chronic
      kidney disease (CKD) whose sodium sensitivity of BP is enhanced. In addition, it
      can maintain the perfusion pressure into important organs including kidneys
      despite lowered systemic BP, and can be used efficiently in combinations with
      many types of antihypertensive agents. On the other hand, most of Ca channel
      blockers dilate mainly preglomerular afferent arterioles, resulting in elevated
      glomerular capillary pressure. Therefore, renal protection by Ca channel blockers
      remains in debate. We will discuss the renal protective action of new Ca channel
      blockers, which can dilate postglomerular efferent arterioles.

PMID- 20048441
TI  - [Calcium antagonists: current and future applications based on new evidence.
      Calcium channel blockers in the elderly with hypertension].
AB  - As calcium channel blocker (CCB) shows high level of tolerance, blood pressure
      lowering effect and organ blood flow, we usefully use to manage the elderly
      hypertensives, and the guideline by Japanese Society of Hypertension in 2009
      reveals as a first line drug. Although there is a few multi-center study about
      the elderly hypertensives, Syst-Eur, NICS-EH, STOP Hypertension-2, PATE
      Hypertension, CASE-J showed CCB could prevent the occurrence of cerebro
      cardiovascular events. CCB also prevents cerebro-cardiovascular events in the
      elderly hypertensives with diabetes. Accumulating these evidences, CCB is very
      useful for treatment of elderly hypertensive patients not only as a first-line
      drug, but also a second or third-line drug.

PMID- 20048442
TI  - [ASBMR 2009 Report. Meeting report on the ASBMR. ASBMR topics].
AB  - This overview summarizes topics from the 31(th) Annual Meeting of ASBMR held at
      Colorado Convention Center in Denver on September 11-15, 2009. Out of the 300
      orally presented papers, I picked up mainly translational and clinical studies,
      focusing on hormones such as PTH, vitamin D, estrogen and FGF23, and new anti
      osteoporotic drugs.

PMID- 20048443
TI  - [ASBMR 2009 Report. Meeting report on the ASBMR. ASBMR topics].
AB  - This is a meeting report on the ASBMR which was held from September 11th to 15th
      2009 in Colorado, Denver. In this report, we focus on recent advances in
      understanding the roles of Wnt signaling in the regulation of bone metabolism.

PMID- 20048444
TI  - [Nutrition and bone health. Food for specified health use (FOSHU) and bone
      health].
AB  - It is known that food has biological regulation functions. The Food for Specified
      Health Use (FOSHU) is the food, of which a functional component was identified,
      of which the biological regulation function has been confirmed in clinical
      trials, and of which a health claim was permitted by the Ministry of Health,
      Labor and Welfare. Currently, three categories of Food for Specified Health Use
      exist concerning bone health: foods helping mineral absorption, foods helping
      mineral absorption and conditioning the intestines, and foods for people
      concerned about bone health. Incorporating Food for Specified Health Use properly
      into diet could help bone health.

PMID- 20048445
TI  - The biochemistry of belief.

PMID- 20048446
TI  - Farmers' suicide: Across culture.

PMID- 20048447
TI  - 'Cinemadness': In search of sanity in films.

PMID- 20048448
TI  - Prayer and healing: A medical and scientific perspective on randomized controlled
      trials.
AB  - Religious traditions across the world display beliefs in healing through prayer.
      The healing powers of prayer have been examined in triple-blind, randomized
      controlled trials. We illustrate randomized controlled trials on prayer and
      healing, with one study in each of different categories of outcome. We provide a
      critical analysis of the scientific and philosophical dimensions of such
      research. Prayer has been reported to improve outcomes in human as well as
      nonhuman species, to have no effect on outcomes, to worsen outcomes and to have
      retrospective healing effects. For a multitude of reasons, research on the
      healing effects of prayer is riddled with assumptions, challenges and
      contradictions that make the subject a scientific and religious minefield. We
      believe that the research has led nowhere, and that future research, if any, will
      forever be constrained by the scientific limitations that we outline.

PMID- 20048450
TI  - Suicide in South India: A community-based study in Kerala.
AB  - BACKGROUND: Studies from Tamil Nadu, South India, have reported the world's
      highest suicide rates. As per official reports, Kerala, another South Indian
      state has the highest suicide rate among the major states in India. OBJECTIVE:
      The purpose of this analysis is to estimate the rates and age-specific incidence
      of suicide in a rural community in Kerala, under continuous observation for the
      last five years. SETTINGS AND DESIGN: The study setting comprised of seven
      contiguous panchayats constituting a development block in Kerala. A prospective
      cohort study design was used. MATERIALS AND METHODS: Through regular home visits,
      every death that occurred in the community was captured by local resident health
      workers and the cause of death assigned. STATISTICAL ANALYSIS: Suicide rates by
      age and sex and relative share of suicide deaths to all-cause deaths in men and
      women were calculated. RESULTS: During the five-year period from 2002 to 2007,
      284 cases of suicide were reported. The suicide rates were 44.7/100,000 for males
      and 26.8/100,000 for females. Male to female suicide ratio was 1.7. Among females
      aged between 15 and 24, suicides constituted more than 50% of all deaths. Male to
      female ratio of suicide varied from 0.4 in children aged 14 years or less to 4.5
      in the 45-54 year age group. CONCLUSION: Our analysis shows that the level of
      under-reporting of suicides in rural Kerala is much less than that reported in
      Tamil Nadu.

PMID- 20048449
TI  - Current perspectives in the treatment of resistant schizophrenia.
AB  - This article summarizes the current knowledge base on the diagnosis and
      management of treatment resistant schizophrenia. While the prevalence of
      treatment resistant schizophrenia is definition dependent, estimates have ranged
      from 30% to up to 60%. This article first looks into the various diagnostic
      criteria of treatment resistant schizophrenia. Then the literature is reviewed
      about the pharmacotherapeutics of its management. Clozapine emerges to be the
      gold standard. In addition risperidone and high dose olanzapine also emerge as
      clinically useful options. Other emerging adjunctive treatment options are
      equally addressed.

PMID- 20048451
TI  - A comparative study of sexual dysfunction involving risperidone, quetiapine, and
      olanzapine.
AB  - BACKGROUND: With the advent of newer antipsychotic drugs, side effects such as
      sexual dysfunction have been a major contributor toward treatment compliance.
      There are only a few studies that have compared different atypical antipsychotic
      agents regarding sexual dysfunction. We have not come across any data in this
      area on Indian population. AIMS: To determine and compare the frequency of sexual
      dysfunction associated with risperidone, olanzapine, and quetiapine, among
      patients with clinically stable schizophrenia. SETTINGS AND DESIGN: It is a cross
      sectional hospital-based study. The subjects were recruited for the study by the
      purposive sampling technique. MATERIALS AND METHODS: The total sample size was
      102, consisting of 25 each in the quetiapine and risperidone groups, 22 in the
      olanzapine group, and 30 healthy volunteers. A Brief Psychiatric Rating Scale and
      Sexual Functioning Questionnaire (SFQ) were administered. The Kruskal Wallis test
      was used to compare the variables in the demographic data and the mean
      chlorpromazine equivalent doses of the study groups. To analyze the sexual
      dysfunction, the mean scores on all the domains of sexual functioning in SFQ were
      compared across the study groups using the Chi square test, for proportions.
      RESULTS AND CONCLUSION: Twenty-three percent of the healthy volunteers had some
      impairment in one or more domains of sexual functioning. For the medication
      groups this was 96, 88, and 90%, respectively for risperidone, quetiapine, and
      olanzapine. However, there was statistically no significant difference across the
      study groups although it was relatively less with quetiapine.

PMID- 20048452
TI  - Clinical practice with antidementia and antipsychotic drugs: Audit from a
      geriatric clinic in India.
AB  - BACKGROUND: Dementia is one of the most disabling disorders afflicting the
      elderly, with a staggering emotional and economic impact. Antidementia agents
      have been used for delaying cognitive decline. Antipsychotics are commonly
      prescribed for behavioral symptoms associated with dementia. OBJECTIVES: To
      explore the use of anti-dementing agents and antipsychotics used in patients with
      a diagnosis of dementia Materials and Methods: A retrospective chart review
      method; geriatric clinic of tertiary care setting. RESULTS: The study sample
      included 51 consecutive patients with a diagnosis of dementia. The commonest
      subtype of dementia that was diagnosed was Alzheimer's disease (45%), followed by
      Frontotemporal dementia (25%).The commonest antidementia drug that was used was
      donepezil, which alone was prescribed in 27 patients (52%). The commonest
      antipsychotic used was quetiapine, which was used in 24 patients (47%).
      CONCLUSIONS: The study found donepezil to be the most commonly prescribed
      antidementia drug and quetiapine to be the most commonly used antipsychotic in a
      tertiary care geriatric clinic, in a developing country. There is a need to study
      the cost-effectiveness of antidementia and antipsychotic drugs in patients with
      dementia, in developing countries.

PMID- 20048453
TI  - Apoptosis in subicular neurons: A comparison between suicide and Addison's
      disease.
AB  - BACKGROUND: Stress and depression shows possible links to neuronal death in
      hippocampus. Subiculum plays a prominent role in limbic stress integration and
      direct effect of corticosteroids on subicular neurons needs to be defined to
      assess its subsequent impact on hippocampal plasticity. AIM: This study was
      intended to assess apoptosis in subicular neurons of a young depressed suicide
      victim, where presumably stress induced excess of corticosteroids and a case of
      young Addison's disease with low level of corticosteroids. MATERIALS AND METHOD:
      Both bilateral adrenal glands (Addison's) and subiculum (both cases) were
      initially stained with hematoxylin and eosin; subicular neurons of both cases
      were examined for the degree of apoptosis using 'ApopTag Kit'. Apoptotic cell
      counts were expressed as average number of labeled cells/mm 2 and the results
      were analysed statistically using a non-parametric Mann-Whitney U test. RESULT:
      Apoptotic neurons were detected in the subicular region of both suicide and
      Addison victims, and it is statistically significant in both right and left
      between the cases (P < 0.05). In suicide victim, the neuronal apoptosis is
      considerably significant between the two hemispheres (P < 0.05), in contrast to
      Addison disease where the number of neuronal cell death between right and left
      was statistically insignificant (P > 0.05). CONCLUSION: The present study
      confirms the vulnerability of the subicular neurons to apoptosis, possibly due to
      corticosteroids in both ends of spectrum.

PMID- 20048454
TI  - Duration of first admission and its relation to the readmission rate in a
      psychiatry hospital.
AB  - BACKGROUND: Most psychiatric illnesses have a chronic relapsing course. It is
      estimated that the readmission rate for discharged patients is approximately 40
      50% within one year of their discharge from the hospital. The current emphasis in
      mental health service is on brief hospitalization and providing community-based
      services. AIM: To understand the relationship between the duration of first
      hospital admission and the rates of readmission in a psychiatry hospital.
      MATERIALS AND METHODS: All the patients admitted at Asha hospital, Hyderabad for
      the first time between16 September, 2003 to 15 March, 2004, were included in the
      study. The hospital records of these patients were examined and the data was
      collected on various variables, which included demographic variables, duration of
      hospital stay, diagnosis, and the number of readmissions for a period of
      approximately three-and-a-half years. The duration of the first hospital stay was
      divided into four categories, Group 1:1-7 days, Group 2:8 to 14 days, Group 3:15
      to 30 days, and Group 4: More than 30 days. RESULTS: The sample consisted of 516
      patients, out of whom 17 were excluded because of insufficient data. Two hundred
      and fifty patients belonged to Group 1 (1 to 7 days), 206 patients in Group 2 (8
      to 14 days), Group 3 (15 to 30 days) constituted 35 patients, and eight patients
      were in Group 4 ( > 30 days). CONCLUSION: The length of the initial hospital stay
      is important to prevent future hospitalization. There are no definite predictors
      for readmission that could be detected, except for the length of the initial
      admission in the study.

PMID- 20048455
TI  - The conceptualization of terms: 'Mood' and 'affect' in academic trainees of
      mental health.
AB  - BACKGROUND: The management of psychiatric disorders should ideally be carried out
      by a multidisciplinary team that consists of mental health professionals from
      different disciplines. All mental health professionals are expected to learn
      similar basic clinical skills during their training, despite the difference in
      their graduation. OBJECTIVE: To compare the conceptualization of the terms 'mood'
      and 'affect' in all academic trainees of mental health in the Central Institute
      of Psychiatry (CIP), Ranchi, India. MATERIALS AND METHODS: The 'modified mood and
      affect questionnaire' administered to all mental health trainees of CIP, Ranchi,
      India, in this study. The participants were requested to mark one response
      (either 'true', 'false' or 'not sure') for each item. The completed questionnaire
      was collected on the spot. RESULTS: The statistical analysis was done for the
      data from psychiatric residents and trainees of clinical psychology. The
      statistical differences were observed between these two groups in response to the
      items-'Mood is the moment to moment emotional tone' and items of 'sign/symptom
      dimension'. CONCLUSIONS: The observed statistical difference in items could be
      the reflection of the differences in the description of 'mood' and 'affect' in
      textbooks of psychopathology, as well as, the difference in their graduation. The
      trainees of clinical psychology may be benefitted with more exposure in medical
      knowledge during their training.

PMID- 20048456
TI  - Experiences of a sensitization program on common mental disorders for primary
      care physicians using problem-based learning approach.
AB  - Authors describe their experience of conducting a series of one-day sensitization
      programs on common mental disorders for primary care doctors. One hundred and two
      doctors attended the program. A problem-based learning approach involving active
      participation by the participants was used. The program was conducted as a part
      of the educational activities under the National Mental Health Program of India.
      It is suggested that this approach can be used effectively to impart training to
      mental health professionals in low-income countries like India.

PMID- 20048458
TI  - Online infidelity: The new challenge to marriages.
AB  - Increased usage of the Internet has given rise to a new challenge to marriages:
      That of online infidelity, which is perceived to be as traumatic as actual
      infidelity. This article highlights the negative impact of online infidelity on
      marital relationship and its detrimental effect on the mental health of the
      offended spouse using a case vignette. The article discusses the importance of
      marital therapy in dealing with the factors contributing to online infidelity and
      in rebuilding marital trust.

PMID- 20048457
TI  - Report of the Indo-US health care summit 2009 - Mental health section.
AB  - The 2nd Indo-US Health Care Summit held in January 2009 was a forum to discuss
      collaboration between physicians in the US and India on medical education, health
      care services and research. Six specialties were represented including Mental
      Health (MH). Using Depression as the paradigmatic disorder, the following
      objectives were developed. Objective I - Leadership and Public Education: Linkage
      with like-minded agencies and organizations. The core message should be simple.
      Major Depression is a brain disorder. Depression is treatable. Timely treatment
      prevents disability and suicide. Objective II - Medical Education: To improve
      psychiatric education, it was proposed that (1) relations between US/UK and
      Indian mid-level institutions be established, (2) teaching methods such as tele
      psychiatry and online courses be pursued, (3) use models of teaching excellence
      to arouse student interest, and (4) develop core curricula for other branches of
      medicine, and CME. Objective III - Reduce Complications of Depression (Suicide,
      Alcoholism): Goals include (1) decriminalizing attempted suicide, (2) improving
      reporting systems, and including depression, psychosis, alcoholism, and suicide
      in the national registry, (3) pilot studies in vulnerable groups on risk and
      interventions, and (4) education of colleagues on alcoholism as a link between
      psychiatric and medical disorders. Objective IV - Integrating MH Treatment&
      Primary Health Care: The focus should be on training of general practitioners in
      psychiatry. Available training modules including long distance learning modules
      to be suitably modified for India. Collaborations and specific project designs
      are to be developed, implemented and monitored by each specialty group and
      reviewed in future summits.

PMID- 20048459
TI  - Dissociative fugue in the elderly.
AB  - Dissociative fugue is a rarely reported diagnostic entity. It is one of the least
      understood and yet clinically one of the most fascinating disorders in Mental
      Health. Here, we describe a case of fugue in a 62-year-old housewife who was
      brought to our hospital with pockets of memory loss. This case illustrates the
      need for timely referrals, which could channelize valuable professional time and
      help avoid expensive and unnecessary investigations.

PMID- 20048460
TI  - Venlafaxine-induced psychotic symptoms.
AB  - Venlafaxine, an antidepressant belongs to Serotonin Norepinephrine Reuptake
      Inhibitors (SNRI), blocks the synaptic reuptake of serotonin in lower doses and
      also blocks reuptake of norepinephrine in higher doses. In addition it also
      blocks dopamine reuptake in still higher doses. This last mechanism of action is
      found to cause psychotic symptoms. Very few cases are reported with this adverse
      effect of venlafaxine. Here is a case report where a 32 year-old male with social
      phobia developed delusions of persecution on two occasions when he was put on
      venlafaxine 150 mg/day, which responded to withdrawal of venlafaxine and a short
      course of antipsychotics. The delusions never reappeared when he was maintained
      on escitalopram.

PMID- 20048461
TI  - Moving towards ICD-11 and DSM-V: Concept and evolution of psychiatric
      classification.
AB  - A classification is as good as its theory. As the etiology of psychiatric
      disorders is still not clearly known, we still define them categorically by their
      clinical syndrome. There are doubts if they are valid discrete disease entities
      and if dimensional models are better to study them. We have come a long way till
      ICD-10 and DSM-IV, but there are shortcomings. With advances in genetics and
      neurobiology in the future, classification of psychiatric disorders should
      improve further. The concept, evolution, current status and challenges facing
      psychiatric classification are discussed in this review.

PMID- 20048462
TI  - Desvenlafaxine.

PMID- 20048463
TI  - The story of antipsychotics: Past and present.

PMID- 20048464
TI  - Amoxapine-induced tardive dyskinesia.

PMID- 20048465
TI  - Obsessive-compulsive disorder of vowels (rare type).

PMID- 20048466
TI  - Toluene associated schizophrenia-like psychosis.

PMID- 20048467
TI  - Return to fitness.
AB  - The cornerstone of personal health is prevention. The concept of exercise as
      medicine is a lesson I have preached throughout my career, both with my patients
      in my private practice as well as through my years working with athletes at all
      levels including the Philadelphia 76ers basketball team and the Pennsylvania
      Ballet. It is also a message I relayed as a Special Advisor to the President's
      Council on Physical Fitness and Sports (PCPFS) during the first Bush
      administration, working closely with my old friend-and fitness advocate and
      visionary himself-Governor Arnold Schwarzenegger, who served as Chairman to the
      PCPFS. Arnold's impact on our nation's health was an extremely positive one that
      was felt in communities from coast-to-coast. Exercise, activity, and prevention
      were key components of his prescription for change and improved health for our
      country. He has also always personally inspired me to see my role as a physician
      and "healer" in a much broader context.

PMID- 20048468
TI  - Effect of fish oil-derived omega-3 polyunsaturated Fatty Acid supplementation on
      exercise-induced bronchoconstriction and immune function in athletes.
AB  - Exercise-induced bronchoconstriction (EIB) is a condition in which vigorous
      physical activity triggers acute airway obstruction in asthmatic and nonasthmatic
      individuals with hyperresponsive airways. Studies have shown that inflammatory
      mediators and contraction of airway smooth muscle are central components in the
      pathogenesis of EIB, and it has long been recognized that leukotrienes and
      prostaglandins play an important role in the EIB response. Clinical responses to
      current therapy, such as leukotriene modifiers and corticosteroids are
      heterogeneous, and even with optimal treatment there is a substantial burden of
      unaddressed disease. While daily medications such as leukotriene modifiers
      provide only modest protection against symptoms, prolonged use of several
      medications can result in reduced effectiveness or tachyphylaxis. Although the
      treatment of EIB almost exclusively involves pharmacotherapy, there is now
      convincing evidence that dietary modification has the potential to reduce the
      severity of this condition. Omega-3 polyunsaturated fatty acids, such as
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oils, compete
      with arachidonic acid as substrates for the formation of proinflammatory
      mediators, such as leukotrienes, prostaglandins, and cytokines. Studies have
      shown that 3 weeks of fish oil supplementation, rich in EPA and DHA, reduces
      exercise-induced airway narrowing, airway inflammation, and bronchodilator use in
      elite athletes and asthmatic individuals with EIB. Based on the evidence to date,
      fish oil supplementation may represent a potentially beneficial treatment
      intervention for athletes and asthmatic individuals with EIB. From this, it
      follows that physicians should pay more attention to what their asthma/EIB
      patients eat, and incorporate dietary assessment and nutritional counseling in
      their everyday practice. KEYWORDS: omega-3; polyunsaturated fatty acid; fish oil;
      exercise-induced bronchoconstriction.

PMID- 20048469
TI  - Grain foods and health: a primer for clinicians.
AB  - Preventing many chronic diseases in North America requires substantial changes in
      dietary habits. Achieving a better balance of grain-based foods through the
      inclusion of whole grains is one scientifically supported dietary recommendation.
      Epidemiological and other types of research continue to document health benefits
      for diverse populations who have adequate intakes of both folic acid-fortified
      grain foods and whole grains. Folic acid fortification of grains is associated
      with reduced incidence of neural tube and other birth defects and may be related
      to decreased risk of other chronic disease. Whole grain intake is associated with
      reduced risk of chronic disease. Specifically, there is a decreased risk of
      obesity, coronary heart disease, hypertension, stroke, metabolic syndrome, type 2
      diabetes, and some cancers observed among the highest whole grain eaters compared
      with those eating little or no whole grains. Nationally promulgated dietary
      recommendations such as those in the US Dietary Guidelines or by health promotion
      organizations such as the American Heart Association have incorporated the
      science on whole grains, recommending that consumers increase their whole grain
      intake. The US Dietary Guidelines state that consumers select half of the
      recommended bread and cereal servings as whole grain. Thus, the recommendations
      recognize the importance of adequate folic acid intake from refined, fortified
      grains to reduce the risk of birth defects and other disorders and to reflect the
      existing science on whole grains. The association between whole grains and
      decreased chronic disease is not surprising because whole grains are a source of
      vitamins, minerals, fatty acids, anti oxidants, and other phytochemicals and
      dietary fiber. Each of these components can act singly or in tandem to contribute
      to specific health-maintaining and disease-preventing mechanisms. Health
      professionals should be aware of these benefits and advocate these dietary
      strategies to help prevent chronic disease and to improve overall health.
      KEYWORDS: nutrition; whole grain; folic acid; disease prevention; diet;
      mortality; diabetes; cereal; pseudocereal; phytochemicals; anti-oxidants.

PMID- 20048470
TI  - The critical role of vitamin B12.
AB  - Vitamin B12 affects the peripheral and central nervous systems, bone marrow, skin
      and mucous membranes, bones, and vessels, as well as the normal development of
      children. Although there is undoubtedly an association between vitamin B12 and
      homocysteinemia, their relative influence on cardiovascular events is
      controversial. Some large studies confirm that a supplementation with group B
      vitamins did not reduce the risk of major cardiovascular events or all-cause
      mortality in patients with vascular disease. The outcomes of these and similar
      trials could have been different had the researchers considered the following
      points: Using vitamin B12 or B-complex as secondary prevention of cardiovascular
      events for patients with irreversible changes of blood vessels is probably in
      error. Rather, vitamin B12 or B-complex should be used as primary prevention.
      Also, using high doses of vitamin B12 will probably be more effective than using
      low doses of "group B vitamins" The effect of vitamin B12 on the proliferation of
      malignant cells has been examined in vivo and in vitro in numerous studies. Their
      results indicate that methylcobalamin inhibits the proliferation of malignant
      cells and propose the possibility of methylcobalamin as a candidate of
      potentially useful agents for the treatment for some malignant tumors. There are
      many articles indicating the increasing prevalence of low vitamin B12 level in
      different segments of general population. In order to prevent serious health
      problems, vitamin B12 routine fortification should be seriously considered and
      discussed. KEYWORDS: vitamin B12; homocysteine; malignancy; vitamin B12 routine
      fortification; recurrent aphthous stomatitis.

PMID- 20048471
TI  - Sacroiliac joint dysfunction: evaluation and treatment.
AB  - Sacroiliac joint (SIJ) dysfunction is once again garnering attention as a
      treatable diagnosis for the millions of individuals suffering from acute and
      chronic low back pain. Theoretically, excessive or restricted motion at the SIJ
      can alter the mechanics of the spine and pelvis causing pain. Oft en the
      clinician's history and physical examination are nonspecific in the evaluation of
      low back pain and a high index of suspicion is required to consider SIJ
      dysfunction as the cause for the patient's symptoms. Multiple physical
      examination maneuvers exist to detect SIJ dysfunction, but none are individually
      sensitive or specific enough to diagnose SIJ dysfunction alone. The clinician
      should learn 3 to 5 tests that can easily be performed and replicated for the
      evaluation of SIJ dysfunction and use them consistently in patients presenting
      with low back pain. Sacroiliac joint anesthetic blocks using computed tomography
      (CT) or fluoroscopic-guided injection are considered the gold standards for
      diagnosing SIJ dysfunction as the cause for nonspecific low back pain. Imaging
      studies and laboratory evaluations are generally unnecessary for the diagnosis of
      SIJ dysfunction unless specific elements of the history and physical suggest
      alternate etiologies. Interventions to treat the pain of SIJ dysfunction include
      nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, corti costeroid
      injections, osteopathic manipulation, radiofrequency denervation, SIJ belts, and
      surgery. While there are few high-level evidence studies evaluating and comparing
      these treatments in individuals with SIJ pain, patients may respond to one, or a
      combination of these treatments. KEYWORDS: sarcoiliac joint; sarcoiliac joint
      dysfunction; spine; low back pain.

PMID- 20048472
TI  - Exercise-associated hyponatremia.
AB  - Disorders of serum sodium concentration occur commonly in athletes participating
      in endurance sports. While hypernatremia is the most commonly seen disorder,
      hyponatremia can occur in 2% to 7% of participants. Hyponatremia is due to a
      combination of excessive water or hypotonic fluid intake as well as high levels
      of arginine vasopressin (or anti diuretic hormone), which limits the ability of
      the kidney to excrete water. Most of these cases are associated with either no or
      minimal side effects and do not require specific therapy other than close
      monitoring and fluid restriction. However, a small number of athletes may present
      with severe and life-threatening hyponatremia associated with cerebral edema and
      possibly noncardiogenic pulmonary edema. Rapid diagnosis and appropriate therapy
      of these symptomatic athletes with hypertonic saline is required to prevent
      severe complications or death. The ability to have rapid on-site measurement of
      serum sodium concentration greatly facilitates accurate diagnosis and therapy.
      Prevention is based on widespread education regarding the risks of overhydration
      and judicious intake of fluids during endurance events. KEYWORDS: hyponatremia;
      cerebral edema; therapy; hypertonic saline.

PMID- 20048473
TI  - Progression of Resistance Training Intensity among Older COPD Patients: A
      Comparison of 2 Resistance Training Studies.
AB  - OBJECTIVE: This comparison study examined strength and functional fitness (FF)
      outcomes between 2 single-set resistance training (SSRT) studies of differing
      intensity progressions (rapid progression [RP] versus delayed progression [DP])
      among elderly pulmonary rehabilitation (PR) patients to determine if there is a
      threshold effect for training intensity. METHODS: Twenty PR patients
      participating in identical hospital-based PR programs, which met twice a week for
      8 weeks, were randomly assigned to SSRT programs, which differed in intensity
      progression (RP: n = 10, mean age = 71.0 +/- 3.7 years; DP: n = 10, mean age =
      65.4 +/- 7.8 years). The SSRT consisted of 1 set of 8 to 15 repetitions of 5
      exercises. For both studies, training loads were determined equally. Load
      increases in the RP study consisted of 5% to 10% immediately following a session
      where 10 repetitions were completed. Load increases for the DP study consisted of
      3 to 5 lbs following 2 consecutive sessions wherein 12 repetitions were
      completed. RESULTS of the primary outcomes data from both SSRT studies were
      compared to determine the presence of a threshold effect for intensity
      progression. The outcomes evaluated in both studies were upper and lower body
      strength and various FF measures. Repeated measures controlling for age,
      pulmonary function, and body mass index (BMI) were used to assess the presence of
      significant differences. To determine statistical significance, alpha was set at
      P < 0.05. RESULTS: Rapid progression resulted in greater increases in upper body
      strength (chest press; P = 0.021) and FF (arm curl test, P = 0.001; lift and
      reach test, P = 0.003) than DP. CONCLUSIONS: Rapid progression of training
      intensity in a SSRT involving elderly PR patients appears superior to delayed
      progression. KEYWORDS: strength training; weight lifting; older adults; exercise
      intensity; pulmonary rehabilitation; COPD.

PMID- 20048474
TI  - Normal resting electrocardiographic variants in young athletes.
AB  - With a growing awareness of the tragedy of sudden cardiac arrest (SCA) in young
      athletes, more extensive pre-participation examinations are being performed prior
      to competitive sport participation. In addition to a history and physical, young
      athletes often have a 12-lead resting electrocardiogram (ECG) to better identify
      heart disease associated with SCA. Complicating this process is that certain
      "abnormal" resting ECG findings are considered normal variants in healthy
      children and young adults. The ability to recognize these normal variants is
      often useful in preventing excessive referral of patients to cardiologists for
      evaluation of resting ECG's that are benign variations of normal and in making
      sound decisions regarding appropriate clearance to exercise. This review
      describes these normal variants. KEYWORDS: normal variants; early repolarization;
      athlete's heart.

PMID- 20048475
TI  - Changing the Face of Hockey: A Study of the Half-Visor's Ability to Reduce the
      Severity of Facial Injuries of the Upper-Half of the Face among East Coast Hockey
      League Players.
AB  - OBJECTIVE: The purpose of the study was to identify the effectiveness of half
      visors by qualitatively comparing the severity, location, and mechanism of facial
      injuries involving the upper-half of the face among an equal number of East Coast
      Hockey League (ECHL) players with and without half-visors. Full visors were not
      included in the study because ECHL players do not wear full visors. DESIGN: A
      stratified sample was retrospectively collected from 5 seasons of ECHL players
      who suffered facial injuries to the upper-half of the face with and without half
      visors. The upper-half of the face is the region purported to be protected by the
      half-visor. A total of 186 injuries were identified to the upper-half of the face
      (93 wore half-visors and 93 wore no protection). SETTING: Johnstown Cambria
      County War Memorial Arena, Johnstown, PA. RESULTS: High-sticking was the most
      common mechanism of injury. Injury severity scores for lacerations with standard
      deviations by injury location (ie, forehead, cheek) were statistically
      significant in the half-visor group when compared with the no-visor group. The
      injury severity scores for contusions due to collisions were statistically higher
      in the no-visor group compared with the half-visor group. CONCLUSIONS: Most
      injury mechanisms occur from an upward trajectory, which could easily slip under
      the half-visor and strike the upper-half of the face and eye region. The half
      visor may not adequately protect the upper-half of the face from common injury
      mechanisms. KEYWORDS: facial protection in hockey; half-visor; hockey facial
      injuries; facial injury mechanisms.

PMID- 20048476
TI  - Exercise-induced anaphylaxis: a serious but preventable disorder.
AB  - Described for the first time approximately 30 years ago, exercise-induced
      anaphylaxis is a rare disorder characterized by development of a severe allergic
      response occurring after mild-to-strenuous physical activity. This disorder is
      especially important to recognize with the recent increase in physical activity
      and health fitness fads. A number of predisposing factors (eg, prior ingestion of
      particular food groups) linked to exercise-induced anaphylaxis has been outlined
      over the years. Mechanisms governing the condition are still being unveiled, and
      it is likely that one mechanism involves mast cell degranulation and inflammatory
      mediator generation resulting from the biochemical effects of exercise, sometimes
      in the presence of an ingested allergen such that wheat or shell fish. Clinical
      manifestations usually occur after around 10 minutes of exercise, and follow a
      specific sequence, starting with pruritis and widespread urticarial lesions,
      evolving into a more typical anaphylactic picture with respiratory distress and
      vascular collapse. Fatality is exceedingly rare, with only one documented case in
      the literature. There is an overlap of symptoms with other syndromes (such as
      systemic mastocytosis and cholinergic urticaria), and these should be remembered
      when establishing a differential. Treatment of exercise-induced anaphylaxis
      consists of immediate stabilization geared toward the anaphylactic response with
      epinephrine and anti histamines. The patient needs to be educated on preventive
      measures and equipped with an epinephrine autoinjector in the event of an
      emergency. Exercise-induced anaphylaxis remains a potentially serious disorder,
      and the health care provider should be aware of its clinical features and
      effective management strategies. KEYWORDS: anaphylaxis; allergy; exercise;
      hypotension; urticaria; asthma.

PMID- 20048477
TI  - Comparison of baseline neuropsychological testing in amateur versus professional
      boxers.
AB  - The aim of the study is to investigate cognitive functions in boxers. The study
      population was composed of 2 groups of male boxers with no history of head
      concussions (except during boxing): a) 33 amateurs at their first examination; b)
      27 professionals. Subjects were requested to: a) fulfill a questionnaire
      collecting demographic data, level of education, occupational status, boxing
      record (for professionals), and number of head concussions during boxing; b)
      undergo a computerized neuropsychological (NP) test (CogSport) measuring simple
      and complex reaction time (RT). Professionals were significantly (P < 0.0001)
      older (29.4 +/- 4.19 years) and started boxing at a younger age (14.5 +/- 3.94 vs
      20.3 +/- 4.77 years, P < 0.0001) than debutants (24.1 +/- 5.13 years). Debutants
      showed significantly shorter simple RTs than professionals, both at the beginning
      (0.244 +/- 0.007 vs 0.249 +/- 0.007 s, P = 0.005) and the end (0.247 +/- 0.007 vs
      0.251 +/- 0.008 s, P = 0.028) of NP test. Complex RTs did not differ between
      groups. Professionals showed a positive significant correlation between simple RT
      at the beginning of NP test and the total number of disputed (P = 0.043) and won
      (P = 0.035) bouts. In conclusion, professionals show a longer simple RT compared
      with debutants, with no difference regarding more complex cognitive tasks. A
      possible explanation may be found in an adaptation of skilled boxers to better
      (and longer) evaluate external stimuli before giving a motor response. KEYWORDS:
      boxing; CogSport; reaction time; neuropsychological test.

PMID- 20048478
TI  - The H-Wave((R)) Device Induces NODependent Augmented Microcirculation and
      Angiogenesis, Providing Both Analgesia and Tissue Healing in Sports Injuries.
AB  - The hypothesis that the H-Wave(R) device (Electronic Waveform Lab, Inc.,
      Huntington Beach, CA), a small-diameter fiber stimulator, is a paradigm shift of
      electrotherapeutic treatment of pain associated with human neuropathies and
      sports injuries is based on a number of its properties. The primary effect of H
      Wave(R) device stimulation (HWDS) is the stimulation of "red-slow-twitch"
      skeletal muscle fibers. The authors propose, based on the unique waveform, that
      the H-Wave(R) device specifically and directly stimulates the small smooth muscle
      fibers within the lymphatic vessels ultimately leading to fluid shifts and
      reduced edema. In unpublished rat studies, it has been observed that HWDS induces
      protein clearance. The H-Wave(R) device was designed to stimulate an ultra low
      frequency (1-2 Hz), low tension, nontetanizing, and nonfatiguing contraction,
      which closely mimics voluntary or natural muscle contractions. The H-Wave(R)
      device can stimulate small fibers due in part to its exponentially decaying
      waveform and constant current generator activity. The main advantage of these
      technologies over currently applied electrical stimulators (eg, transcutaneous
      electrical nerve stimulator [TENS], interferential [IF], neuromuscular electrical
      stimulation [NMES], high-volt galvanic, etc.) is that H-Wave?'s(R) small fiber
      contraction does not trigger an activation of the motor nerves of the large white
      muscle fibers or the sensory delta and C pain nerve fibers, thus eliminating the
      negative and painful effects of tetanizing fatigue, which reduces transcapillary
      fluid shifts. Another function of the H-Wave(R) device is an anesthetic effect on
      pain conditions, unlike a TENS unit which in the short term activates a
      hypersensory overload effect (gate theory) to stop pain signals from reaching the
      thalamic region of the brain. When the H-Wave(R) device is used at high frequency
      (60 Hz), it acts intrinsically on the nerve to deactivate the sodium pump within
      the nerve fiber, leading to a long-lasting anesthetic/analgesic effect due to an
      accumulative postsynaptic depression. Moreover, HWDS produces a nitric oxide (NO)
      dependent enhancement of microcirculation and angiogenesis in rats. Thus, the
      authors hypothesize that because of these innate properties of the H-Wave(R)
      device, it may provide a paradigm shift for the treatment of both short- and long
      term inflammatory conditions associated with pain due to sports injuries. A
      recent meta-analysis found a moderate-to-strong effect of the H-Wave(R) device in
      providing pain relief, reducing the requirement for pain medication, and
      increasing functionality. The most robust effect was observed for improved
      functionality, suggesting that the H-Wave(R) device may facilitate a quicker
      return to the field. KEYWORDS: H-Wave(R) device; sportsmedicine, nitric oxide
      dependent blood flow; analgesia; angiogenesis.

PMID- 20048479
TI  - Pancreatic Injury Following Blunt Abdominal Trauma during a Soccer Game.
AB  - This article reports a case of unusual pancreatic trauma, underestimated
      initially and treated surgically at a later stage. A 26-year-old man presented
      with an abdominal trauma sustained during a soccer game. The patient arrived 24
      hours after the trauma with abdominal pain associated to vomiting and intestinal
      occlusion. Laboratory tests revealed elevated serum amylase levels. An abdominal
      computed tomography (CT) scan showed a pancreatic parenchymal dishomogeneity at
      the passage between body and tail, highly suspicious for pancreatic full
      thickness laceration. Magnetic resonance pancreatography (MRP) demonstrated
      possible duct involvement. The patient was urgently submitted to distal
      pancreatectomy with splenectomy. This case demonstrates a rare mechanism of
      injury and the potential importance of serial CT scans in the diagnosis, grading,
      and management of isolated pancreatic injury. KEYWORDS: pancreatic injury; blunt
      abdominal trauma; pancreas; duct disruption.

PMID- 20048480
TI  - Female athlete triad in monozygotic twins.
AB  - Female monozygotic twins, both international endurance athletes aged 18 years,
      presented for a dual energy x-ray absorptiometry (DXA) scan as part of a
      university clinical trial. Twin 1 had only menstruated twice since menarche; Twin
      2 had not yet started menstruating. Both twins acknowledged suffering from
      disordered eating for approximately 3 years. Both twins presented with low lumbar
      spine bone mineral density (BMD) and normal total body, total hip, and femoral
      neck BMD. DIAGNOSIS: Female athlete triad comprising disordered eating with
      insufficient energy availability, amenorrhea, and low age-related BMD.
      MANAGEMENT: Despite some weight gain and reduction of athletic training and
      competition over a 5-year period, lumbar BMD remained low in both twins and was
      complicated by a rapid decline in BMD at the hips. Twin 2 remained amenorrheic.
      The oral contraceptive pill was not effective in maintaining BMD in the other
      twin. Contraindicated treatment with bisphosphonates was not tolerated and
      promptly ceased. This case seminar emphasizes the absence of a clear physician
      coordinated multi-disciplinary treatment approach and the complexity in treating
      all the components of the triad in young athletes. KEYWORDS: female athlete
      triad; monozygotic; amenorrhea; bone mineral density.

PMID- 20048481
TI  - Focal motor seizure in a wrestler with a sport-related concussion.
AB  - Although sport-related concussion is a common injury, it is infrequently
      associated with seizure. While concussive convulsions, consisting of brief,
      generalized myoclonic activity while an athlete is unconscious have been
      described, the authors are aware of no published cases of concussion complicated
      by focal motor seizures. The authors describe the case of a 16-year-old male
      wrestler who sustained a sport-related concussion complicated by a focal motor
      seizure. The acute assessment and management of his injury, as well as follow-up
      until resolution of his symptoms, is presented. A brief review of the association
      between convulsive activity and mild traumatic brain injury follows. KEYWORDS:
      concussion; mild traumatic brain injury; seizure.

PMID- 20048482
TI  - Measuring the efficacy of antihypertensive therapy by ambulatory blood pressure
      monitoring in the primary care setting.
AB  - This study demonstrates the efficacy of ambulatory blood pressure monitoring to
      measure anti hypertensive effect. Original Article: White WB, Giles T, Bakris GL,
      Neutel JM, Davidai G, Weber MA. Measuring the efficacy of antihypertensive
      therapy by ambulatory blood pressure monitoring in the primary care setting. Am
      Heart J. 2006;151(1):176-184. KEYWORDS: anti hypertensive therapy; blood
      pressure; hypertension.

PMID- 20048483
TI  - Independent and combined effects of aerobic exercise and pharmacological
      strategies on serum triglyceride concentrations: a qualitative review.
AB  - Elevated fasting and postprandial serum triglyceride concentrations are
      associated with cardiovascular disease morbidity and mortality. Aerobic exercise
      reduces serum triglyceride concentrations in the presence or absence of weight
      loss. Although pharmacological interventions are often used in combination with
      aerobic exercise to achieve target triglyceride concentrations, information on
      the combined effects of aerobic exercise and lipid-modifying agents on serum
      triglycerides is limited. This review examines the independent and combined
      effects of both interventions on serum fasting and postprandial triglyceride
      concentrations from the available literature. Reductions in serum triglycerides
      after aerobic exercise are associated with an increase in skeletal muscle
      lipoprotein lipase activity and a decrease in hepatic triglyceride and very-low
      density lipoprotein (VLDL) synthesis and secretion. Lipid-modifying agents such
      as niacin, omega-3 fatty acids, and statins also decrease fasting and
      postprandial triglycerides by increasing lipoprotein lipase (LPL) activity and/or
      decreasing VLDL synthesis. When combined, lipid-modifying agents may reduce
      fasting and postprandial triglyceride secretion to an extent in which aerobic
      exercise cannot provide any additional benefit. These observations indicate that
      aerobic exercise and pharmacological strategies reduce serum triglycerides by
      similar mechanisms, which may attenuate the triglyceride-lowering capacity of the
      concordant treatment.

PMID- 20048484
TI  - Intramyocellular lipids: effect of age, obesity, and exercise.
AB  - Obese individuals with metabolic syndrome are predicted to have a 5 times greater
      risk of developing type 2 diabetes and a 3 times greater risk of myocardial
      infarction than those without metabolic syndrome. Many obese patients with
      metabolic risk factors have an accumulation of triglycerides within the skeletal
      muscle fibers, ie, intramyocellular lipids (IMCL). Individuals with metabolic
      syndrome have a greater risk of developing IMCL depots, and these stores are
      related to increased cardiovascular risk and type 2 diabetes. A few studies have
      shown, moreover, that aging seems to result in an increase in IMCL stores,
      although little is known about how exercise influences these stores. In healthy
      young individuals, IMCL depots have been shown to decrease in response to acute
      exercise, but very little is known about the effects of exercise training on IMCL
      depots in obese individuals. Understanding how IMCL depots can be altered with
      exercise (both resistance and aerobic exercise) in older and obese individuals
      seems to be critical in preventing disease.

PMID- 20048485
TI  - Acute exercise does not attenuate postprandial oxidative stress in prediabetic
      women.
AB  - Individuals with impaired lipid and glucose metabolism are at increased risk for
      postprandial oxidative stress. Acute exercise can attenuate the rise in both
      blood triglyceride (TAG) and glucose, and increase antioxidant enzyme activity
      after food intake, which may decrease the oxidative stress response. This study
      investigated the effect of acute exercise on blood TAG and oxidative stress
      biomarkers in prediabetic women. Sixteen prediabetic women (30 +/- 3 years of
      age; fasting blood glucose, 107 +/- 3 mg x dL(-1); body mass index, 32 +/- 2 kg x
      m(-2)) consumed a high-fat meal with and without a session of aerobic exercise 15
      minutes preceding the meal (45-minute duration, 65% heart rate reserve), in a
      random order cross-over design. Blood samples were collected premeal (fasted) and
      at 1, 2, 4, and 6 hours postmeal and assayed for Trolox equivalent antioxidant
      capacity (TEAC), xanthine oxidase (XO) activity, hydrogen peroxide (H2O2),
      malondialdehyde (MDA), TAG, and glucose. No interaction or condition main effects
      were noted (P > 0.05). However, time main effects were noted for XO, H2O2, MDA,
      and TAG (P < 0.0001), with values higher from 1 to 6 hours postmeal compared with
      premeal, and for TEAC (P = 0.05), with values lower at 4 hours postmeal. Glucose
      remained relatively unchanged (P > 0.05). Acute exercise, performed at the
      intensity and duration of the present study, does not influence postprandial TAG
      and oxidative stress in obese prediabetic women. Such individuals may need a
      greater volume of exercise for measurable effects.

PMID- 20048486
TI  - The effect of lean fish consumption on triglyceride levels.
AB  - Marine omega-3 fatty acids have an important role in reducing the risk of
      coronary artery disease (CAD). The American Heart Association recommends 1 g/day
      of omega-3 fatty acids for patients with CAD, and for those without CAD, the
      consumption of a variety of fish (preferably fatty fish) at least twice a week is
      recommended. Greater amounts of omega-3 fatty acids (4 g per day) are recommended
      to treat hypertriglyceridemia. Fish oil capsules are often needed to provide the
      greater quantities of omega-3 fatty acids necessary to treat
      hypertriglyceridemia, which should not obscure the important triglyceride
      lowering effects of seafood consumption. The effects of fish consumption on
      plasma lipids and lipoproteins are well described in studies that have generally
      been conducted with fatty fish and fish oil capsules. This study of a group of
      men and women in a strictly controlled dietary setting showed that compared with
      a cholesterol-free diet, both lean fish and beef diets raised plasma low-density
      lipoprotein cholesterol levels, but the fish diet resulted in lower levels of
      plasma total cholesterol, very-low-density lipoprotein (VLDL) triglycerides, and
      VLDL cholesterol, while the beef diet resulted in higher plasma high-density
      lipoprotein cholesterol levels. These findings can help practitioners to extend
      their dietary recommendations to incorporate significant quantities of low-fat
      fish to reduce triglyceride levels.

PMID- 20048487
TI  - Does bicycling contribute to erectile dysfunction? Examining the evidence.
AB  - Bicycling is a popular means of recreation, transport, and fitness training for
      many people around the world, but questions have been raised about its threat to
      sexual function. This review summarizes some of the data on whether cycling is or
      is not an independent risk factor for erectile dysfunction and other sexual
      complaints. Space limitations will confine our discussion to men, although these
      problems are also important in women.

PMID- 20048488
TI  - Current concepts: recognition and management of common activity-related
      gastrointestinal disorders.
AB  - Sports medicine clinicians may encounter a wide variety of activity-related
      gastrointestinal (GI) disorders. The advancing ages and burgeoning obesity rates
      of the US population have generally increased the prevalence of GI conditions
      among adults. However, conditioned younger athletes with normal body mass indices
      also may experience disquieting activity-related GI disorders. While often mild
      and transient, some of these GI conditions may disrupt exercise routines or pose
      significant health risks to affected individuals. Gastroesophageal reflux occurs
      frequently during physical activity and should be empirically treated with
      activity reduction and dietary modifications in conjunction with antisecretory
      agents. Persistent or worrisome symptoms merit upper endoscopy, a thorough
      evaluation for non-GI causes and, rarely, surgery. Altered GI motility commonly
      occurs during vigorous activities that use dynamic or fluctuating body positions.
      Dietary and exercise modifications are usually enough to resolve these symptoms.
      Physical activity may also precipitate GI bleeding from upper and/or lower
      sources. Although mild or occult bleeding is most common, significant bleeding
      merits a thorough diagnostic evaluation after stabilization and treatment.
      Adequate hydration and gradual exercise progression may be particularly helpful
      to prevent the recurrence of bleeding. The judicious use of medications in
      conjunction with nonsteroidal anti-inflammatory drug avoidance may also be
      necessary. Fortunately, most activity-related GI disorders are self-limited and
      can be managed conservatively. After a brief period of modified activity,
      clinically stable individuals may progress their activity levels as symptoms
      allow.

PMID- 20048489
TI  - Original research: long-term efficacy and safety of periarticular hyaluronic acid
      in acute ankle sprain.
AB  - The objectives of this study were to determine the long-term efficacy and safety
      of periarticular hyaluronic acid (HA) injections in acute lateral ankle sprain. A
      randomized, controlled, prospective trial in a primary sports medicine and
      emergency practice involved 158 competitive athletes who suffered an acute grade
      1 or 2 lateral ankle sprain, and who were randomly assigned within 48 hours of
      injury. Patients were randomly assigned at baseline to periarticular injection
      with HA + standard of care (rest, ice, elevation, and compression [RICE]) or
      placebo injection (PL) + standard of care (RICE) treatment at baseline assessment
      and day 4 after injury. Follow-up was at 30, 90, and 712 days after treatment.
      Assessments at baseline and days 4, 8, 30, 90, and 712 included visual analogue
      scale (VAS) (0-10 cm) pain on weight bearing and walking 20 m, patient global
      assessment of ankle injury (5-point categorical scale), patient satisfaction with
      treatment (5-point categorical scale), time to return to pain-free and disability
      free sport, recurrent ankle sprain, total number of days missing from primary
      sport activity, and adverse events (AEs). Time to intervention was 39 +/- 4 hours
      with no difference between groups. A significant reduction in VAS pain on both
      weight bearing and walking was observed at all follow-up assessments for HA
      compared with PL (P < 0.001). Time to pain-free and disability-free return to
      sport was 11 (+/- 8) versus 17 (+/- 8) days for HA and PL, respectively (P <
      0.05). At 24 months, in the PL versus HA group, there were 2 versus 0 lower limb
      fractures, 16 versus 7 second ankle sprains (P < 0.05), 3 versus 1 third ankle
      sprains, and a significantly greater number of days missing primary sport
      activity (41 vs 21; P < 0.002). Significantly greater patient satisfaction was
      also observed for HA versus PL at all follow-up assessments. No serious AEs were
      recorded throughout follow-up. Periarticular HA treatment for acute ankle sprain
      was highly satisfactory in the short and long term versus PL. This was associated
      with reduced pain, more rapid return to sport, fewer recurrent ankle sprains,
      fewer missed days from sport, and with few associated AEs to 24 months.

PMID- 20048490
TI  - Exertional rhabdomyolysis and acute kidney injury.
AB  - Skeletal muscle breakdown occurs normally with exercise, followed by muscle
      repair and physiologic adaptation. Strenuous, unaccustomed, prolonged, and
      repetitive exercise, particularly when associated with other risk factors such as
      hot and humid climate or sickle cell trait can cause clinically significant
      exertional rhabdomyolysis (ER). Although most cases are asymptomatic and resolve
      without sequelae, ER is the most common cause of exercise-related myoglobinuric
      acute renal injury and acute renal failure in athletes. Exercise-related muscle
      pain, elevated serum creatine kinase (CK), and "cola-colored" urine have been
      described as a classic presentation of ER. The exact mechanism of ER has not been
      clearly elucidated. Most studies suggest a cascade of events that include
      depletion of adenosine triphosphate (ATP), impaired function of the Na+- K+
      ATPase system, intracellular excess calcium accumulation, sarcolemma damage, and
      release of intracellular proteins and other substances into blood. Excess
      myoglobin that is filtered at the glomerulus can lead to myoglobinuric acute
      renal injury. Cessation of physical activity, relative rest during clinical
      recovery, and early aggressive fluid replacement are mainstays of treatment.
      Return to play after recovery from ER is influenced by associated risk factors
      that may predispose the athlete to recurrence and is guided by signs, symptoms,
      and CK levels. This article reviews the definitions, pathophysiology, diagnosis,
      and management of ER with specific relevance to acute kidney injury.

PMID- 20048491
TI  - Return-to-play decisions in athletes with cardiac conditions.
AB  - Many sets of guidelines written by experts in their fields can assist sports
      medicine physicians to make return-to-play decisions for athletes with known or
      suspected cardiac conditions. These guidelines can be divided into pre
      participation screening guidelines, such as the 2007 American Heart Association
      (AHA) 12-element screening examination, and specific recommendations for those
      with heart disease or symptoms. Several important documents fall into the latter
      category. Among these are the 36th Bethesda Guidelines, the European Society of
      Cardiology Guidelines, the AHA Consensus Document for Young People with Genetic
      Conditions, the Heart Rhythm Society Guidelines, and the Guidelines for Masters
      Athletes. Guidelines are designed to enhance the sports medicine physician's
      probability of detecting heart disease and making wise participation and return
      to-play decisions in athletes with high-risk cardiac conditions, such as
      hypertrophic cardiomyopathy, anomalous coronary artery, myocarditis, and valvular
      heart disease. Guidelines also aid in writing exercise prescriptions for those
      deemed too high risk for sports participation. Because the guidelines may not be
      entirely consistent on all topics, or based on opinion rather than research
      evidence, many cases require additional input from a cardiologist or
      electrophysiologist. Guidelines address not only specific disease entities, but
      also how corrective surgery, ablations, implantable defibrillators, or drug
      therapy can influence return-to-play decisions. They are updated as new studies
      become available to provide physicians with the most up-to-date information.

PMID- 20048492
TI  - Upper extremity injuries in golf.
AB  - Golf is an asymmetric sport with unique patterns of injury depending upon the
      skill level. Higher handicap players typically experience injuries that result
      from swing mechanics, whereas lower handicap and professional players have
      overuse as the major cause of their injuries. The majority of shoulder injuries
      affecting golfers occur in the nondominant shoulder. Common shoulder injuries
      include subacromial impingement, rotator cuff pathology, glenohumeral
      instability, and arthritis involving the acromioclavicular and/or glenohumeral
      joints. Lead arm elbow pain resulting from lateral epicondylosis (tennis elbow)
      is the leading upper extremity injury in amateur golfers. Tendon injury is the
      most common problem seen in the wrist and forearm of the golfer. Rehabilitation
      emphasizing improvement in core muscle streng is important in the treatment of
      golf injury. Emerging treatments for tendinopathy include topical nitrates,
      ultrasound-guided injection of therapeutic substances, and eccentric
      rehabilitation. There is evidence supporting physiotherapy, and swing
      modification directed by a teaching professional, for treatment of upper
      extremity golf injuries. This article focuses on upper extremity injuries in
      golf, including a discussion of the epidemiology, causes, diagnosis, treatment,
      and prevention of injuries occurring in the shoulder, elbow, wrist, and hand.

PMID- 20048493
TI  - Clinical examination of scaphoid fractures.
AB  - Undetected scaphoid fractures may lead to complications, including nonunion,
      malunion, avascular necrosis, and wrist arthritis. A competent physical
      examination is essential for the diagnosis of scaphoid fractures in the setting
      of occult fractures presenting with normal radiographs. The differential
      diagnosis of occult scaphoid fractures includes acute tears of the scaphoid
      lunate ligament, Kienbock's disease, occult ganglion, nondisplaced radial styloid
      fractures, and injury to the radial aspect of the radio-scapho-capitate ligament.
      All of these may have normal plain radiographs but often can be distinguished
      based on physical examination findings. The 2 key points of such an examination
      include the exact location of point tenderness and provocative special tests.
      Although Watson's scaphoid shift test is classically described for scaphoid
      instability, we highlight its significance in the setting of scaphoid fractures.

PMID- 20048494
TI  - Effects of low-intensity exercise on patients with peripheral artery disease.
AB  - BACKGROUND: Peripheral artery disease (PAD) is one of the many unhealthy
      conditions that may get worse with age. Its most common symptom is intermittent
      claudication (IC). Intermittent claudication is the exercise-induced ischemic
      pain caused by the reduced blood flow to the lower extremities. OBJECTIVES: To
      investigate the effects of low intensity treadmill walking on the functional
      capacity of PAD patients with IC. Walking ability (time, rate, and distance),
      heart rate, and blood pressure responses were recorded before, during, and after
      each exercise session. Only the initial and final values recorded were used for
      data analysis. This 6-week program of low-intensity, pain-free endurance training
      was designed to keep the exercise level low enough to minimize ischemic leg pain.
      METHODS: Thirteen PAD patients volunteered for twice weekly exercise sessions for
      6 consecutive weeks. Each session consisted of a 10-minute warm-up consisting of
      routine, pain-free static and proprioceptive neuromuscular facilitation
      stretching. Each patient exercised for 10 to 20 minutes as tolerated on the
      treadmill. Proprioceptive neuromuscular facilitation was conducted following
      walking. RESULTS: As a group the patients with PAD had an average 148%
      improvement in distance, 34% in rate, and 94% in duration of walking. Five of the
      13 patients had over 100% improvement in distance, with the maximum being 525%.
      One of the 13 patients had a 100% improvement in rate. Four of the 13 patients
      had over 100% improvement in duration, with the maximum being 500%. CONCLUSIONS:
      This study introduces a new method of low-intensity treadmill walking exercise,
      which seems to be an effective nonpharmacologic treatment even within a 6-week
      period for patients with IC due to PAD. It also supports the benefits of walking
      exercise to increase the mobility of these patients, thus improving functional
      capacity of life.

PMID- 20048495
TI  - Body image, disordered eating, and anabolic steroids in male bodybuilders:
      current versus former users.
AB  - PURPOSE: To examine body image, disordered eating, and psychological
      characteristics typically observed in people with eating disorders in current,
      former, and nonsteroid-using male bodybuilders. METHODS: Fifty bodybuilders
      recruited from local gymnasia completed anonymous questionnaires designed to
      assess eating attitudes, body image, weight and shape preoccupation, and general
      psychological characteristics. Ten subjects were classified as currently using
      anabolic-androgenic steroids, 12 were former users, and 28 had never used
      steroids. RESULTS: Compared with former users and non-users, current steroid
      users reported higher scores on weight and shape preoccupation, body
      dissatisfaction, drive for increased muscle tone, depression, ineffectiveness,
      perfectionism, and interpersonal distrust. No differences emerged between former
      users and non-users. CONCLUSIONS: Current but not previous anabolic-androgenic
      steroids use is associated with considerable body image disturbance, eating
      related psychopathology, and poorer psychological adjustment. Theoretical and
      clinical implications of these findings are discussed.

PMID- 20048496
TI  - Independence: a new reason for recommending regular exercise to your patients.
AB  - There are many good reasons to advise regular and adequate physical activity:
      longevity seems extended by up to 2 years, and the risk of a wide range of
      chronic disorders is substantially reduced. However, from the viewpoint of the
      overall, quality-adjusted lifespan, perhaps the most important reason is the
      ability of physical activity to counter the relentless, age-related decrease in
      physical capacity (maximal aerobic power, muscle strength, flexibility, and
      balance). The case is detailed for maximal aerobic power, which deteriorates by
      about 5 mL/ [kg x min] for each decade of adult life. Independence is generally
      at risk when the maximal oxygen intake has dropped to 18 mL/ [kg x min] in men
      and 15 mL/ [kg x min] in women. A sedentary person typically reaches this
      threshold between 80 and 85 years old. However, regular physical activity can
      augment maximal oxygen transport by 5 to 10 mL/ [kg x min], setting back the need
      for institutional support by 10 to 20 years.

PMID- 20048497
TI  - Exercise and the aging mind: buffing the baby boomer's body and brain.
AB  - Among the fears of aging are loss of memory, cognitive decline, and loss of
      independence. Baby boomers have entered the "aged" cohort and are actively
      seeking ways to maintain strong bodies and strong minds. Bench to clinical
      research suggests that keeping physically active and engaged in moderate to
      vigorous exercise may be vital to brain health. Because exercise promotes
      neurogenesis, increased brain volume, and improved cognitive function, it can
      help the aging brain to retain plasticity. However the precise mechanisms by
      which exercise accomplishes these changes in the brain are not clearly
      understood. This study argues that "what is good for the heart is good for the
      brain," although more research is needed to determine the optimal exercise
      prescription for brain health and successful cognitive aging.

PMID- 20048498
TI  - Case report: exercise-associated hyponatremia with rhabdomyolysis during
      endurance exercise.
AB  - Exercise-associated hyponatremia (EAH) has been well described in the literature,
      and its pathogenesis has been elucidated. The most common presenting symptoms of
      EAH are confusion or severe alterations in mental status. Although rhabdomyolysis
      in association with hyponatremia has been described in other settings, only 1
      case of EAH associated with rhabdomyolysis at presentation has been previously
      described. In this article, we report on the occurrence of EAH with
      rhabdomyolysis in 4 athletes participating in the West Highland Way Race, a 95
      mile endurance foot race. The pathogenesis of this association is described with
      implications for therapy.

PMID- 20048499
TI  - Case report: a case of persistent back pain and constipation in a 5-year-old boy.
AB  - Pediatric intramedullary spinal cord tumors are rare and account for 3% to 6% of
      all central nervous system tumors. Astrocytomas are infiltrating neoplasms, and
      they predominate in the pediatric population. We report a case of an
      intramedullary spinal cord astrocytoma in a 5-year-old boy with nonspecific mid
      back pain for 3 months. Physical examination revealed clonus, thoracolumbar
      tenderness, and pain with sitting straight leg raises. An urgent magnetic
      resonance imaging showed an intramedullary tumor in the mid-thoracic cord,
      confirmed by surgical excision. The physician should maintain a high index of
      suspicion when evaluating the pediatric patient who presents with unexplained and
      persistent back pain. Associated findings, including nocturnal pain and
      neurological symptoms may indicate a more serious underlying pathology such as a
      tumor. Early detection, prompt treatment, and proper post surgical management
      will often lead to improved outcomes in patients.

PMID- 20048500
TI  - Case report: injuries associated with interactive game consoles: preliminary
      data.
AB  - The use of motion-sensing video game software has provided users with the ability
      to mimic movements in many sports such as baseball, tennis, and boxing.
      Epidemiology on injuries and overuse of motion-sensing video game systems is
      minimal because the systems have only been available for 2 years. This case
      series report presents preliminary data on injuries related to the game systems
      from the first full year of use. Methods included the use of secondary data from
      the National Electronic Injury Surveillance System for 2007. The query found 21
      cases of injury related to the use of the "Wii" video game system (Nintendo of
      America Inc., Redmond, WA). Results indicated that females were more prone to
      injuries, and the mean age was 16 years. Most injuries were soft tissue in nature
      and located in the shoulders, hands and fingers, and the face and neck region.
      Our discussion includes prevention strategies for reducing injury risk when
      playing motion-sensing video games.

PMID- 20048501
TI  - Questioning the efficacy of antihypertensive therapy by ambulatory blood pressure
      monitoring in the primary care setting.
AB  - PRACTICE PEARL: This study demonstrates the efficacy of ambulatory blood pressure
      monitoring to measure antihypertensive effect. Original Article: White WB, Giles
      T, Bakris GL, Neutel JM, Davidai G, Weber MA. Measuring the efficacy of anti
      hypertensive therapy by ambulatory blood pressure monitoring in the primary care
      setting. Am Heart J. 2006;151(1):176-184.

PMID- 20048502
TI  - The association of depressive symptoms with prediabetes versus diagnosed
      diabetes: is ignorance really bliss?
AB  - PRACTICE PEARL: Although unrecognized prediabetes (impaired fasting glucose
      and/or impaired glucose tolerance) is not associated with concurrent depressive
      symptoms, screening for development of depression in individuals with
      treated/recognized type 2 diabetes remains important. Original Article: Rhee MK,
      Musselman D, Ziemer DC, et al. Unrecognized glucose intolerance is not associated
      with depression. Screening for Impaired Glucose Tolerance study 3 (SIGT 3).
      Diabet Med. 2008;25(11):1361-1365.

PMID- 20048503
TI  - Effectiveness of the early addition of rosiglitazone to control hyperglycemia
      after unsuccessful submaximal sulphonylurea monotherapy: the Rosiglitazone Early
      Versus SULphonylurea Titration (RESULT) Study.
AB  - Practice Pearl: This study demonstrates the effectiveness of the early addition
      of rosiglitazone to control hyperglycemia after unsuccessful submaximal
      sulphonylurea monotherapy. Original Article: Rosenstock J, Goldstein BJ, Vinik
      AI, et al. RESULT Study Group. Effect of early addition of rosiglitazone to
      sulphonylurea therapy in older type 2 diabetes patients (> 60 years): the
      Rosiglitazone Early vs. SULphonylurea Titration (RESULT) study.

PMID- 20048504
TI  - Are you 3-d fit?

PMID- 20048505
TI  - Protein for exercise and recovery.
AB  - Dietary protein is required to promote growth, repair damaged cells and tissue,
      synthesize hormones, and for a variety of metabolic activities. There are
      multiple sources of proteins available; however, animal sources of protein
      contain all essential amino acids and are considered complete sources of protein,
      whereas plant proteins lack some of the essential amino acids and are therefore
      classified as incomplete. There is a significant body of evidence to indicate
      that individuals who are engaged in intense training require more dietary protein
      than sedentary counterparts (ie, 1.4-2 g/kg/day). For most individuals, this
      level of protein intake can be obtained from a regular and varied diet. However,
      recent evidence indicates that ingesting protein and/or amino acids prior to,
      during, and/or following exercise can enhance recovery, immune function, and
      growth and maintenance of lean body mass. Consequently, protein and amino acid
      supplements can serve as a convenient way to ensure a timely and/or adequate
      intake for athletes. Finally, adequate intake and appropriate timing of protein
      ingestion has been shown to be beneficial in multiple exercise modes, including
      endurance, anaerobic, and strength exercise.

PMID- 20048506
TI  - New data on the clinical impact of exercise training, fish oils, and statins in
      heart failure.
AB  - Despite major advances in the field of cardiovascular (CV) diseases, heart
      failure (HF) continues to result in considerable CV morbidity and mortality and
      accounts for an increasing number of acute hospitalizations in adult patients.
      Recent major trials have focused on exercise training programs and the widely
      available nutraceutical omega-3 polyunsaturated fatty acids or fish oil and
      statins in patients with HF. In this article, we provide insight into the
      interpretation of the evidence base for these distinct interventions in HF and
      provide guidance for the clinical incorporation of exercise training and fish oil
      therapy for additional CV protection in chronic HF.

PMID- 20048507
TI  - Proposed role of calcium and dairy food components in weight management and
      metabolic health.
AB  - Dietary calcium and dairy foods have demonstrated an antiobesity effect in animal
      studies, observational and population studies, and randomized clinical trials.
      Moreover, there is a strong theoretical framework to explain the effects of
      dietary calcium on energy metabolism. The supporting mechanisms include dietary
      calcium-correcting suboptimal calcium intakes, thereby preventing the endocrine
      response (parathyroid hormone [PTH] and calcitriol), which favors adipocyte
      energy storage and inhibits adipocyte loss via apoptosis. Dietary calcium appears
      to further promote energy loss via formation of calcium soaps in the
      gastrointestinal tract and thereby modestly reduces net energy absorption.
      Dietary calcium appears to be responsible for approximately 50% of the
      antiobesity bioactivity of dairy foods. The additional dairy bioactivity has not
      been fully identified, but is primarily localized in whey protein. The major
      components are the angiotensin-converting enzyme (ACE) inhibitor activity of whey
      proteins and the high concentration of leucine in whey. This high leucine content
      appears to be primarily responsible for the repartitioning of dietary energy from
      adipose tissue to skeletal muscle during weight loss, resulting in greater
      preservation of skeletal muscle and accelerated loss of adipose tissue during
      negative energy balance. Finally, high-calcium diets suppress obesity-induced
      oxidative and inflammatory stress independently from its role in modulating
      adiposity; these effects are similarly augmented by other dairy food components.
      However, the number of randomized clinical trials conducted is still modest, and
      a small number have not confirmed significant effects in weight management. Thus,
      the protective effects of dairy foods against obesity and its comorbidities are
      promising, but warrant further large-scale studies.

PMID- 20048508
TI  - Tennis: for the health of it!
AB  - Tennis is a sport with numerous health benefits for individuals of all ages. It
      is also a tremendously effective fitness activity. Regular participants
      experience a wide variety of health-related physical and mental benefits, from
      improved cardiovascular, metabolic, and bone health to improved agility,
      coordination, and even stress and anxiety management. Physicians and other health
      care professionals can play an important role in educating patients and the
      public about the health benefits of tennis as well as motivating them to take up
      this activity as part of an overall exercise prescription. Based on the
      scientific evidence available, it is difficult to find an activity that offers as
      wide a range of overall health benefits as tennis, and individuals who take up
      tennis reap tremendous rewards.

PMID- 20048509
TI  - Prescribing physical activity: applying the ACSM protocols for exercise type,
      intensity, and duration across 3 training frequencies.
AB  - When physicians advise patients to attain more physical activity, they usually
      recommend a walking program. However, in a similar way to no exercise, those
      embarking on a walking program will typically lose 4 to 6 lb of lean weight and
      reduce their resting metabolic rate 2% to 3% every decade. These effects may be
      mitigated by the inclusion of resistance exercise. The American College of Sports
      Medicine (ACSM) minimum exercise guidelines recommend 20 minutes of aerobic
      activity 3 days per week, and 1 set (8-12 repetitions) of 8 to 10 resistance
      exercises to train the major muscle groups 2 days per week. However, large-scale
      testing of these recommendations in a field setting has been minimal. Men and
      women between 21 and 80 years (N = 1725) [corrected] participated in a 10-week
      combined strength and aerobic activity program based on the ACSM protocols for
      exercise intensity and duration across 3 training frequencies (1, 2, or 3
      sessions/week). Across all training frequencies, mean changes included a
      reduction in body fat of 1.97%, a decrease in fat weight of 1.7 kg, an increase
      in lean weight of 1.35 kg, a reduction in systolic blood pressure of 3.83 mm Hg,
      and a reduction in diastolic blood pressure of 1.73 mm Hg. More frequent weekly
      training sessions were associated with greater improvements in body fat percent,
      fat weight, and lean weight. Participants responded favorably to the ACSM
      exercise program with a 91% completion rate and a 95% satisfaction rating. This
      article presents recommendations for prescribing safe, effective, and time
      efficient exercise programs.

PMID- 20048510
TI  - Rhegmatogenous retinal detachment.
AB  - Patients often present after trauma with symptoms of vision loss or loss of a
      field of vision from a rhegmatogenous retinal detachment (RRD). This study aims
      to equip the health care provider with knowledge on the recognition, evaluation,
      and management of RRD to improve communication between the patient and
      consultant. The article highlights the symptoms, signs (including ophthalmoscopic
      findings), and pathogenesis of RRD. Causes and presentations of RRD are
      considered. Treatment paradigms are discussed and surgical options for treatment
      of RRDs are reviewed, including pneumatic retinopexy, pars plana vitrectomy, and
      scleral buckle surgery.

PMID- 20048511
TI  - beta(2)-Adrenergic agonist administration and strength training.
AB  - beta(2)-Adrenergic agonists (beta(2)AA) produce myriad effects throughout the
      human body. Prescribed concurrently with theophylline for the bronchodilatory
      effects they offer in the treatment of asthma and chronic obstructive pulmonary
      disease, beta(2)AA actions include many beneficial and adverse changes when
      administered to animals at supraphysiological doses. Beneficial changes include
      improved musculoskeletal health and function, which can be maintained because
      adverse changes are reduced if oral beta(2)AA are given at therapeutic dosages in
      humans with concurrent resistive exercise administration. Combined oral beta(2)AA
      resistive exercise treatments have been shown to produce gains in musculoskeletal
      health and function in numerous healthy and disuse atrophy human models. The
      mechanism(s) by which beta(2)AA exert their effects are a function of multiple
      factors, not the least of which includes the type of model receiving the drug
      treatment. Combined oral beta(2)AA-resistive exercise treatments in humans showed
      that adverse effects were greatly reduced when prudent and safer drug
      administration practices were employed (eg, screening subjects for tolerance
      before drug treatment). Results from human research trials suggest that
      administration of the combined treatment improves musculoskeletal function and
      performance with minimal health risk if proper precautions are followed. A
      related issue is administration of the combined treatment as an ergogenic aid to
      athletic performance. Given the results presented in this article, physicians
      should be wary of potential drug abuse and administer beta(2)AA only under
      appropriate circumstances when such a treatment is warranted.

PMID- 20048512
TI  - An approach to the diagnosis and treatment of plantar fasciitis.
AB  - Plantar fasciitis is a painful condition affecting many athletes. Anatomic and
      biomechanical factors combined with overuse can contribute to its genesis.
      Correction of gait disturbances, changes in footwear, use of tension night
      splints, and stretching of tight calf and plantar tissues have all be proven to
      relieve symptoms. Anti-inflammatory modalities, including medications,
      iontophoresis, and corticosteroid injection generally provide temporary
      improvement. Recent studies on the efficacy of extracorporeal shock wave therapy
      are conflicting. Injections with platelet-rich plasma or sclerotic agents are
      currently under investigation for use in this and other similar conditions. A
      small percentage of patients with refractory symptoms may benefit from surgical
      release of the plantar fascia. Diagnosis and correction of biomechanical factors
      leading to this condition should be a mainstay of treatment and may prevent
      recurrences.

PMID- 20048513
TI  - Foot pain: biomechanical basics as a guide for assessment and treatment.
AB  - A large percentage of Americans will likely have a foot problem in their
      lifetime. Foot pain has a multitude of diagnoses; however, most can be properly
      diagnosed with a basic understanding of the biomechanics of gait. For pain-free
      ambulation, human feet go through a series of rotatory motions involving
      pronation and supination. Pathologic biomechanics are generally divided into
      excessive pronation or excessive supination. Treatment is often directed at
      minimizing the pathologic biomechanical forces to assist with pain-free walking.

PMID- 20048514
TI  - Biomechanical analysis of stresses to the fifth metatarsal bone during sports
      maneuvers: implications for fifth metatarsal fractures.
AB  - Fifth metatarsal stress fractures are an increasing problem in elite and
      recreational athletic populations. One possible mechanism of injury is the many
      bending moments applied to the fifth metatarsal during dynamic sports maneuvers
      involving rapid changes in direction and speed. A potentially important bending
      moment is loading of the base versus the head of the fifth metatarsal, which
      tends to cause a bending moment along the bone. To determine which maneuver
      applies the greatest pressure differential between the base and head of the fifth
      metatarsal, 10 college-aged male athletes performed running straight, jump take
      off, jump landing, cutting right, cutting left, and accelerating while plantar
      pressures were recorded using a Pedar insole system (Novel Electronics, Inc., St.
      Paul, MN). Peak pressure at the fifth metatarsal base was subtracted from the
      peak pressure at the fifth metatarsal head to obtain the fifth metatarsal
      pressure differential-a corollary to the bending moment. The greatest fifth
      metatarsal pressure differential was observed during acceleration maneuvers (20 +
      or - 13.1 N/cm(2); P < 0.0001) followed by running straight (11.6 + or - 8
      N/cm(2); P < 0.0008). The other maneuvers had low pressure differentials: jump
      take-off (4.2 + or - 10.6 N/cm(2)), jump landing (3.7 + or - 9.2 N/cm(2)),
      cutting left (2.3 + or - 4.2 N/cm(2)), and cutting right (-2.1 + or - 10
      N/cm(2)). It appears that acceleration maneuvers may apply the largest bending
      moments to the fifth metatarsal and could lead to stress fractures. Because fifth
      metatarsal stress fractures are associated with rapid increases in training
      volume, reducing the number of acceleration events may be effective in altering
      the balance between bone resorption and bone formation and reducing stress
      fracture risk. Careful planning of training programs allowing for adequate rest
      between intense bouts of exercise involving many acceleration maneuvers may be
      the best preventative measure.

PMID- 20048515
TI  - Ankle instability in sports.
AB  - Ankle stability is integral to normal motion and to minimizing the risk of ankle
      sprain during participation in sport activities. The ability of the dynamic and
      static stabilizers of the ankle joint to maintain their structural integrity is a
      major component of the normal gait cycle. In sports, this quality assumes even
      greater importance given the range of movement and stresses imposed on the ankle
      during various sporting disciplines. In the general population, the incidence of
      ankle sprain is very high. In several studies, injuries to the lateral ankle
      ligaments have been shown to be the most common sports-related injuries,
      accounting for approximately 25% of all sports-related injuries. Furthermore, up
      to 80% of all ankle sprains involve the lateral ligament complex. Other studies
      have estimated their incidence as approximately 5000 injuries per day in the
      United Kingdom and 23 000 in the United States. Aggressive treatment of the
      sprained ankle is essential to maintain foot and ankle mobility and prevent
      prolonged disability and subsequent overuse injuries among athletes, both
      professional and "weekend warriors" alike.

PMID- 20048516
TI  - Technique and safety aspects of resistance exercises: a systematic review of the
      literature.
AB  - A systematic review of the scientific literature was conducted to identify the
      optimal ranges of motion for preventing injury in the main joints of the body
      during resistance exercise performance. These ranges of motion are independent of
      the type in which the resistance exercises could be applied (ie, adults, elderly,
      athletes, recreational exercisers), and the regions examined include the
      shoulder, spine, and knee, which are injured most often. It can be concluded that
      during the performance of any resistance exercise, it is possible to put
      anatomical structures at risk with certain body positions; therefore, it is
      necessary to understand these movements so injury can be avoided.

PMID- 20048517
TI  - Basketball clinic educates asthmatic children.
AB  - Healthy Hoops Kentucky is a new and innovative health program in Jefferson
      County, Kentucky that teaches asthmatic children (9-13 years) and their families
      how to manage the disease through the appropriate use of medications, proper
      nutrition, monitored exercise, and recreational activities. The Healthy Hoops
      Kentucky program includes asthma screenings at selected YMCA after-school care
      facilities and community health fairs, asthma awareness seminars for sports and
      school coaches, and a half-day basketball event held once a year, featuring local
      university coaches and current and former college basketball players.

PMID- 20048518
TI  - Cardiorespiratory responses to maximal arm and leg exercise in national-class
      marathon runners.
AB  - Marathon runners (MR) are among the most aerobically fit athletes in the world.
      Although aerobic capacity (VO(2)max) during arm exercise generally varies between
      64% and 80% of leg VO(2)max (mean 70%) in healthy men, few data are available
      regarding the comparative arm fitness of MR. To clarify the relationship between
      arm and leg fitness in MR, we studied 10 national-class MR (mean + or - standard
      deviation age 30 + or - 4 years) whose best marathon times averaged < 2 hours and
      40 minutes. Each MR underwent lower and upper body maximal exercise evaluations
      with measurement of cardiorespiratory variables using indirect calorimetry during
      treadmill testing (standard Bruce protocol) and arm-crank ergometry,
      respectively. Our subjects achieved VO(2)max levels equaling 75.8 + or - 7.1
      mL/kg/min (5.2 + or - 0.6 L/min) during treadmill testing, which was
      significantly higher than the level of cardiorespiratory fitness achieved during
      maximal arm exercise (45.4 + or - 12.4 mL/kg/min [3.1 + or - 0.9 L/min]; P <
      0.01). In addition, maximal heart rate (183.2 + or - 8.2 vs 163.7 + or - 10 bpm)
      and systolic blood pressure (201.8 + or - 10.1 vs 186.6 + or - 12.1 mm Hg) were
      significantly higher (P < 0.01 and P < 0.05, respectively) during maximal leg
      versus arm exercise. Relative arm fitness (arm VO(2)max/leg VO(2)max) was
      extremely variable (41%-76%), averaging 60% + or - 13%. Although MR are able to
      achieve significantly higher VO(2)max values during treadmill testing than those
      observed in the general population, their relative arm fitness appears to be
      slightly reduced. These findings add to and strongly support the specificity of
      measurement and training concept.

PMID- 20048519
TI  - A lower-limb training program to improve balance in healthy elderly women using
      the T-bow device.
AB  - Ageing impairs balance, which increases the risk of falls. Fall-related injuries
      are a serious health problem associated with dependency and disability in the
      elderly and results in high costs to public health systems. This study aims to
      determine the effects of a training program to develop balance using a new device
      called the T-Bow. A total of 28 women > 65 years were randomly assigned to an
      experimental group (EG) (n = 18; 69.50 [0.99] years), or a control group (CG) (n
      = 10; 70.70 [2.18] years). A program for lower limbs was applied for 8 weeks
      using 5 exercises on the T-Bow: squat, lateral and frontal swings, lunges, and
      plantarflexions. The intensity of the exercises was controlled by time of
      exposure, support base, and ratings of perceived exertion. Clinical tests were
      used to evaluate variables of balance. Static balance was measured by a 1-leg
      balance test (unipedal stance test), dynamic balance was measured by the 8-foot
      up-and-go test, and overall balance was measured using the Tinetti test. Results
      for the EG showed an increase of 35.2% in static balance (P < 0.005), 12.7% in
      dynamic balance (P < 0.005), and 5.9% in overall balance (P > 0.05). Results for
      the CG showed a decline of 5.79% in static balance (P > 0.05) but no change in
      the other balance variables. Thus the data suggest that implementing a training
      program using the T-Bow could improve balance in healthy older women.

PMID- 20048520
TI  - Case report: peptic ulcer disease in a professional athlete.
AB  - Peptic ulcer disease (PUD) is a common problem that affects 4 million people in
      the United States. Although its prevalence has not been studied in the athletic
      population, one would suspect PUD would affect athletes at a similar rate or
      higher based on the predispositions to certain risk factors of this disease. This
      case report addresses the particular predispositions for PUD in a professional
      football athlete.

PMID- 20048521
TI  - Consensus statement on concussion in sport - the Third International Conference
      on Concussion in Sport held in Zurich, November 2008.
AB  - This paper is a revision and update of the recommendations developed following
      the 1st (Vienna) and 2nd (Prague) International Symposia on Concussion in Sport.
      The Zurich Consensus statement is designed to build on the principles outlined in
      the original Vienna and Prague documents and to develop further conceptual
      understanding of this problem using a formal consensus-based approach. A detailed
      description of the consensus process is outlined at the end of this document
      under the "background" section (see Section 11). This document is developed for
      use by physicians, therapists, certified athletic trainers, health professionals,
      coaches and other people involved in the care of injured athletes, whether at the
      recreational, elite, or professional level. While agreement exists pertaining to
      principal messages conveyed within this document, the authors acknowledge that
      the science of concussion is evolving, and therefore management and return-to
      play (RTP) decisions remain in the realm of clinical judgment on an
      individualized basis. Readers are encouraged to copy and distribute freely the
      Zurich Consensus document and/or the Sports Concussion Assessment Tool (SCAT2)
      card, and neither is subject to any copyright restriction. The authors request,
      however, that the document and/or the SCAT2 card be distributed in their full and
      complete format.

PMID- 20048522
TI  - Addition of extended-release niacin to statin therapy: effects on atherosclerotic
      progression.

PMID- 20048523
TI  - Effects of aerobic exercise on non-high-density lipoprotein cholesterol in
      children and adolescents.

PMID- 20048524
TI  - Chronic kidney disease, exercise, and sports in children, adolescents, and
      adults.
AB  - Individuals with chronic kidney disease have poor exercise tolerance and are
      easily fatigued compared with their healthy peers. The primary reasons for poor
      exercise tolerance include anemia, effects of chronic uremia and metabolic
      acidosis on the heart and skeletal muscles, and lower levels of physical
      activity. Studies suggest that regular and early implementation of both aerobic
      and resistance exercise programs in persons with chronic kidney disease have
      positive effects on muscle function, exercise tolerance, and quality of life.
      Before starting any exercise program, a medical assessment and exercise testing
      are generally recommended. No consensus exists regarding allowing young athletes
      with a solitary kidney who want to participate in contact or collision sports.
      Decisions to allow participation in different sports and leisure activities
      should be made on an individual basis, considering multiple factors. This article
      reviews factors that affect exercise tolerance in persons with chronic kidney
      disease, the effects of exercise, and exercise recommendations.

PMID- 20048525
TI  - Features and management of compulsive exercising in eating disorders.
AB  - Compulsive exercising is a common feature of patients with eating disorders. It
      is reported more frequently by patients with restricting-type anorexia nervosa
      than with other eating disorders. It is associated with higher eating disorder
      psychopathology, dietary restraint, general psychopathology, and specific
      personality features (ie, higher levels of perfectionism, persistence, and lower
      novelty seeking). It is a potent maintaining mechanism of eating disorder
      psychopathology, and it increases the risk of overuse injuries, bone fractures,
      and cardiac complications. It also appears to be a predictor of poor treatment
      outcome. Literature are lacking regarding its treatment, but cognitive-behavioral
      therapy in its enhanced form appears to be a promising treatment in hospitalized
      patients.

PMID- 20048526
TI  - Impact of psychosocial risk factors on the heart: changing paradigms and
      perceptions.
AB  - To combat cardiovascular disease (CVD), physicians and allied health care
      professionals often focus on modifying conventional risk factors such as
      cigarette smoking, hypertension, hypercholesterolemia, and diabetes. However, a
      recent review of published research demonstrated that 75% to 90% of coronary
      artery disease (CAD) incidence is explained by these risk factors, either alone
      or in combination. This has stimulated a vigorous search for other correctable
      risk factors (ie, to explain the remaining incidence [10%-25%]), including
      genetic anomalies, markers of inflammation (C-reactive protein, lipoprotein
      associated phospholipase A2), and specific lipid/lipoprotein particles to enhance
      risk stratification. Nevertheless, an escalating body of research provides strong
      evidence for the adverse effects of psychosocial factors in the development of
      CVD and in the prognosis of patients with CAD.

PMID- 20048527
TI  - Functional improvement with hylan G-F 20 in patients with knee osteoarthritis.
AB  - A systematic review of randomized, controlled, prospective clinical studies is
      described (8 trials; N = 1674 patients), with > 100 patients in each, which
      evaluated functional outcomes with hylan G-F 20 in secondary analyses. Hylan G-F
      20 significantly improved Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC) physical function versus appropriate/conventional
      care or corticosteroid, it significantly improved loss of activity versus saline,
      and it had similar functional improvements compared with progressive knee
      exercises or nonsteroidal anti-inflammatory drugs. Functional improvements with
      hylan G-F 20 also improved with pain relief. Hylan G-F 20 should be considered as
      part of a multimodal arthritis treatment regimen that focuses on improving
      function.

PMID- 20048528
TI  - Reducing the risk of noncontact anterior cruciate ligament injuries in the female
      athlete.
AB  - High school and collegiate female athletes have a significantly increased risk of
      sustaining a noncontact anterior cruciate ligament injury compared with male
      athletes participating in the same sport. This review summarizes the current
      knowledge of the risk factors hypothesized to influence this problem, and the
      neuromuscular training programs designed to correct certain biomechanical
      problems noted in female athletes. The risk factors include a genetic
      predisposition for sustaining a knee ligament injury, environmental factors,
      anatomical indices, hormonal influences, and neuromuscular factors. The greatest
      amount of research in this area has studied differences between female and male
      athletes in movement patterns during athletic tasks; muscle strength, activation,
      and recruitment patterns; and knee joint stiffness under controlled, preplanned,
      and reactive conditions in the laboratory. Neuromuscular retraining programs have
      been developed in an attempt to reduce these differences. The successful programs
      teach athletes to control the upper body, trunk, and lower body position; lower
      the center of gravity by increasing hip and knee flexion during activities; and
      develop muscular strength and techniques to land with decreased ground reaction
      forces. In addition, athletes are taught to preposition the body and lower
      extremity prior to initial ground contact to obtain the position of greatest knee
      joint stability and stiffness. Two published programs have significantly reduced
      the incidence of noncontact anterior cruciate ligament injuries in female
      athletes participating in basketball, soccer, and volleyball. Other programs were
      ineffective, had a poor study design, or had an insufficient number of
      participants, which precluded a true reduction in the risk of this injury. In
      order to determine which risk factors for noncontact anterior cruciate ligament
      ruptures are significant, future investigations should include larger cohorts of
      athletes in multiple sports, analyze factors from all of the major risk
      categories, and follow athletes for at least one full athletic season. Future
      risk assessment studies should incorporate reactive tasks under more realistic
      sports conditions.

PMID- 20048529
TI  - Effects of a 12-month randomized controlled trial of aerobic or resistance
      exercise during and following cancer treatment in women.
AB  - Weight gain is common during and following cancer treatment and contributes to
      many adverse health consequences and increased risk of recurrence for cancer
      survivors. The purpose of this longitudinal randomized controlled trial was to
      compare differences in weight change and body composition among newly diagnosed
      cancer survivors receiving chemotherapy who were randomly assigned to usual care
      control, aerobic exercise, or resistance exercise interventions. It was
      hypothesized that cancer survivors become more sedentary during treatment,
      leading to positive energy balance that in turn worsens body composition. One
      hundred one subjects completed the 12-month study. Data collected included body
      composition (body weight and dual energy x-ray absorptiometry scan), aerobic
      capacity (12-minute walk), and muscle strength (1 repetition maximum). Aerobic
      exercisers were found to have significant improvements in body composition,
      aerobic capacity, and muscle strength. Resistance exercisers also benefitted, but
      were less compliant with the intervention over time. Thus, exercise during and
      following cancer treatment is an important intervention to maintain and perhaps
      improve body composition of cancer survivors, which may improve survival, reduce
      comorbidities, and improve quality of life.

PMID- 20048530
TI  - Individualized 12-week exercise training programs enhance aerobic capacity of
      cancer survivors.
AB  - Changes in aerobic capacity were evaluated after 12 weeks of training among a
      motivated heterogeneous group of cancer survivors (N = 54 [41 women and 13 men]),
      living at moderate altitude. Changes in power at lactate threshold (PT(lact)),
      peak power (P(peak)), and peak oxygen uptake (VO(2) peak) were evaluated in this
      group (average age, 53.8 + or - 10.8 years) that completed a minimum of 12 weeks
      of an individualized exercise program (on average 5 days x week(-1) for 47.5 + or
      - 17.2 min x session(-1)). Daily exercise duration was based on the goals and
      functional capacity of each individual. Training intensity for each subject was
      based on heart rate (HR) value at lactate threshold (T(lact)) obtained during a
      symptom-limited cardiopulmonary exercise test. Intensity was categorized into 5
      ranges: recovery (60%-80% HR T(lact)); endurance (80%-100% HR T(lact)); threshold
      (100%-105% HR T(lact)); intervals (105%-115% HR T(lact)); and maximal efforts (>
      or = 115% HR T(lact)). Overall compliance with the exercise prescription was
      approximately 72% and subjects reported exercising within the 5 training ranges,
      12.1%, 63.9%, 18.6%, 4.2%, and 1.2% of the time, respectively. After training,
      PT(lact) increased 9.5% (121.8 + or - 43.5 vs 133.2 + or - 34.1 W; P < 0.05),
      P(peak) increased 12.6% (175.5 + or - 55.6 vs 195.6 + or - 54.2 W; P < 0.05) and
      VO(2) peak increased 11.4% (33.4 + or - 12.5 vs 37.2 + or - 10.4 mL x kg(-1) x
      min(-1); P < 0.05). The results of this research indicate that: 1)
      cardiopulmonary exercise testing with lactate threshold determination was safe
      and effective in the evaluation and exercise prescription phase for a group of
      cancer survivors and 2) a training program based on 2 higher intensity workouts
      per week can elicit significant changes in aerobic capacity of a diverse group of
      cancer survivors.

PMID- 20048531
TI  - Exercise training before and after lung transplantation.
AB  - The benefits of exercise training in individuals with chronic lung diseases such
      as chronic obstructive pulmonary disease, cystic fibrosis, and interstitial lung
      disease have been well documented. Although there is limited research available,
      it appears that exercise is safe and beneficial for people with severe end-stage
      chronic lung disease who are awaiting lung transplantation in addition to
      recipients of lung transplants. Evidence-based guidelines for exercise training
      in the pre- and post-lung transplantation phases have not yet been developed.
      However, by considering exercise guidelines for people with chronic lung disease
      and in older adults in light of the physiological changes that can occur either
      pre- or post-lung transplantation, a safe and appropriate exercise training
      program can be developed. Depending on the individual's exercise capacity and
      goals, the training program may include aerobic and resistance exercise, and
      flexibility and balance training. In the pre-transplant and acute post-transplant
      phases, the intensity of exercise is dictated primarily by symptom limitation and
      adequate rest, which is required between exercise bouts to allow for recovery. In
      the post-transplant phase, it is possible for lung transplant recipients to
      increase their exercise capacity and even participate in sports. Further research
      needs to be conducted to determine the optimal training guidelines and the long
      term benefits of exercise, both in lung transplant candidates and recipients.

PMID- 20048532
TI  - The effect of whole body vibration short-term exercises on respiratory gas
      exchange in overweight and obese women.
AB  - AIMS: To assess the effect of whole body vibration on oxygen uptake and carbon
      dioxide production among overweight and obese women. METHODS: In a randomized
      controlled trial, anthropometric measurements were taken in 20 adult overweight
      women. Ventilation of oxygen, carbon dioxide, and heart rate were measured using
      a portable gas-analysis system. After each exercise, a Borg's scale score was
      assessed. Exercises were performed on a vibration platform with a frequency of 35
      Hz and with the intensity set on "high" (amplitude of 4 mm). Two dynamic
      exercises (squatting and calf raises) and one static exercise (standing) were
      performed during 3 minutes with and without vibration in a randomized order, with
      10 minutes rest between exercises. Mean values of the third minute of exercise
      were compared. RESULTS: Ventilation of oxygen and carbon dioxide were
      consistently, significantly higher in the exercises with vibration compared with
      the exercises without vibration. Borg's scale scores only showed a significant
      difference between calf raises with and without vibration. CONCLUSION: The
      addition of whole body vibration to both static and dynamic exercises appears to
      significantly increase oxygen uptake in overweight and obese women. More research
      is needed to determine the physiological pathway and clinical relevance of this
      increase.

PMID- 20048533
TI  - SCOUT trial reports on the safety profile of sibutramine in patients with
      cardiovascular diseases.

PMID- 20048534
TI  - Longitudinal assessment of bariatric surgery study evaluates physical activity
      levels of bariatric surgery candidates.

PMID- 20048535
TI  - Congratulations to the physician and sportsmedicine team for being accepted into
      the National Library of Medicine!

PMID- 20048536
TI  - Health care reform: hope for change.

PMID- 20048537
TI  - Summary of the National Athletic Trainers' Association position statement on the
      acute management of the cervical spine-injured athlete.
AB  - The incidence of catastrophic cervical spine injury in sports is low compared
      with other injuries. However, cervical spine injuries necessitate delicate and
      precise management, often involving the combined efforts of a variety of health
      care providers. The outcome of a catastrophic cervical spine injury depends on
      the efficiency of this management process and timeliness of transfer to a
      controlled environment for diagnosis and treatment. The objective of the National
      Athletic Trainers' Association (NATA) position statement on the acute care of the
      cervical spine-injured athlete is to provide the certified athletic trainer, team
      physician, emergency responder, and other health care professionals with
      recommendations on how to best manage a catastrophic cervical spine injury in an
      athlete. Recommendations are based on current evidence pertaining to prevention
      strategies to reduce the incidence of cervical spine injuries in sport; emergency
      planning and preparation to increase management efficiency; maintaining or
      creating neutral alignment in the cervical spine; accessing and maintaining the
      airway; stabilizing and transferring the athlete with a suspected cervical spine
      injury; managing the athlete participating in an equipment-laden sport such as
      football, hockey, or lacrosse; and imaging considerations in the emergency
      department.

PMID- 20048538
TI  - The acute effects of local vibration therapy on ankle sprain and hamstring strain
      injuries.
AB  - AIMS: The purpose of this study was to determine if biomechanical muscle
      stimulation (BMS) applied directly to different segments of the body using the
      Swisswing device results in acute improvements in range of motion and perceived
      stiffness in physically active adults with acute or subacute ankle sprain and
      hamstring strain injuries. METHODS: Two separate groups of individuals with grade
      I or II ankle sprain (n = 5; 21.2 +/- 1.9 years) or hamstring strain (Nn= 5; 20.6
      +/- 1.8 year) underwent 20 minutes of a controlled therapy consisting of ice,
      compression, and elevation, and 10 minutes of segmental BMS using the Swisswing
      at 20 Hz. Ankle (dorsiflexion, plantar flexion, inversion, eversion), hamstring
      flexibility, and subjective ratings of stiffness were assessed prior to control
      treatment (baseline), post-control treatment, and post-Swisswing treatment.
      RESULTS: Relative to the post-control condition, Swisswing treatment
      significantly (P < 0.03 for all) increased ankle dorsiflexion and eversion and
      hamstring flexibility, and significantly (P <or= 0.05) decreased perceived ankle
      and hamstring stiffness. CONCLUSION: Segmental BMS therapy using the Swisswing
      device appears to have significant acute benefits for improving flexibility and
      reducing perceived stiffness in healthy adults with ankle or hamstring injury.
      Future research is needed to determine the duration of these effects and if
      repeated periods of segmental BMS therapy aid in long-term injury recovery.

PMID- 20048539
TI  - Current developments concerning medial tibial stress syndrome.
AB  - Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries
      in athletes who run. Studies have reported MTSS to occur in 4% to 20% of this
      population. It can be defined as an overuse injury that creates pain over an area
      covering the distal to middle third of the posteriomedial tibial border, which
      occurs during exercise and creates cyclic loading. Differential diagnosis
      includes ischemic disorders and stress fractures. Although the pathology of this
      injury is understood, the etiology is less agreed upon. This makes it difficult
      for clinicians to diagnose and treat this common injury. The purpose of this
      article is to present health care practitioners with the most current information
      regarding MTSS so they can better diagnose and treat this common injury. To this
      end, a literature review was conducted, with the most current results presented.
      The areas of etiological theories, imaging techniques, and treatment options for
      MTSS were searched. Five of the most prevalent etiological theories are presented
      with supporting evidence. Of the imaging tools available to the clinician,
      magnetic resonance imaging (MRI) and bone scintigraphy have comparable
      specificity and sensitivity. Clinicians should first make the clinical diagnosis
      of MTSS, however, because of high percentages of positive MRI scans in
      asymptomatic patients. There have been few randomized controlled trials
      investigating treatment options for athletes with MTSS. Those that have been
      performed rendered no significant findings, leading researchers to conclude that
      rest is equal to or better than other treatment options. Given the evidence,
      treatment suggestions for practitioners caring for athletes with MTSS are
      provided.

PMID- 20048540
TI  - Computerized neuropsychological profiles of South African versus US athletes: a
      basis for commentary on cross-cultural norming issues in the sports concussion
      arena.
AB  - Computerized programs are widely used as part of the overall medical management
      of concussion in order to monitor recovery and facilitate safe return-to-play
      decisions. Typically, neurocognitive profiles of concussed athletes are compared
      with baseline and/or normative data in the absence of baseline scores. However,
      the cultural equivalence of performance on neuropsychological tests cannot be
      assumed and has not been sufficiently researched. The purpose of this study was
      to investigate the neuropsychological test profiles of the ImPACT (Immediate
      Postconcussion Assessment and Cognitive Testing) on age-matched South African
      (SA) rugby and US football players. Participants included 11 257 English
      speaking, predominantly white male athletes from multiple SA and US schools and
      sports organizations in 3 age groups: 11 to 13 years (SA, n = 301; US, n = 775);
      14 to 16 years (SA, n = 997; US, n = 4081); and 17 to 21 years (SA, n = 319; US,
      n = 4784). ImPACT neurocognitive composite scores (verbal and visual memory,
      visual motor speed, reaction time, impulse control) and the ImPACT total symptom
      score, derived from the initial baseline testing, were used for comparison
      purposes between the targeted groups. Independent t-test comparisons revealed
      overall equivalence between the SA and US athletes on the neurocognitive
      measures, but they also revealed consistently higher symptom scores for SA
      athletes in association with clinically relevant effect sizes. It was concluded
      that US neurocognitive normative data on the ImPACT test are appropriate for use
      on South African athletes whose first language is English, whereas culture
      specific sensitivity for symptom reporting on this same population should be
      taken into consideration for management purposes. It is argued that
      neurocognitive equivalence is less likely to apply in educationally disadvantaged
      populations. The use of registered psychologists is deemed necessary to provide
      contextualized interpretations of computerized test scores, thereby protecting
      against misdiagnosis that may occur within the concussion management arena via
      actuarial approaches that fail to take sociocultural complexities into account.

PMID- 20048541
TI  - Sports after knee arthroplasty: partial versus total knee arthroplasty.
AB  - Osteoarthritis becomes more prevalent with increasing age, and currently is
      occurring more frequently in the "baby boomer" generation (ages 44-66 years).
      However, many individuals may be reluctant to undergo arthroplasty procedures
      because potential activity limitations. Thus, physicians must consider each
      patient's history and desired activity level after treatment. Osteoarthritis
      treatments include nonoperative measures such as weight reduction, injections,
      and nonsteroidal anti-inflammatory drugs, as well as operative options, including
      partial and total knee arthroplasty. Each treatment type will vary in its impact
      on activity levels. If arthroplasty is required, patients must be cautioned to
      minimize component overload, which may result in polyethylene wear and loosening;
      however, cardiopulmonary fitness and general conditioning benefits of activity
      can be maintained.

PMID- 20048542
TI  - Physician follow-up care for osteoporosis after fragility fractures.
AB  - Osteoporosis affects > 10 million Americans each year. The disease is
      characterized by low bone mass and decreased bone strength, and patients often
      sustain fragility fractures. Previous research highlights low rates of
      identification and treatment of the disease after a fragility fracture, yet
      patients are still overlooked. This study identified patients who did not receive
      proper osteoporosis care after a fragility fracture in Southeastern Pennsylvania.
      In a telephone interview, we asked patients who had sustained a fragility
      fracture in 2008 and were treated at one orthopedic practice about information on
      events before and after their fractures. We concluded that a patient's bone
      health had suboptimal care if, after the fracture, the patient had no doctor
      interview, did not receive bone mineral density testing, and did not begin or
      change medications. Of the 224 patients who participated in our study, we
      determined that 149 (67%) patients received insufficient osteoporosis care. One
      hundred fourteen (63%) women and 35 (80%) men received inadequate osteoporosis
      care. The high incidence of unsatisfactory care, particularly in men, indicates
      that osteoporosis care continues to be a problem. We believe that one
      contributing factor is physician accountability for care. Our study indicates
      that no specific specialist takes responsibility for follow-up care, possibly
      signifying the lack of an adequate system for identifying and treating the
      disease. The opportunity to address this issue should be a high priority for both
      primary care physicians and orthopedic surgeons.

PMID- 20048543
TI  - Examining the degree of pain reduction using a multielement exercise model with a
      conventional training shoe versus an ultraflexible training shoe for treating
      plantar fasciitis.
AB  - Plantar fasciitis is a common injury to the plantar aponeurosis, manifesting as
      pain surrounding its proximal insertion at the medial calcaneal tubercle. Pain is
      typically worse in the morning when getting out of bed, and may subside after the
      tissue is sufficiently warmed up. For running-based athletes and individuals who
      spend prolonged periods of time on their feet at work, plantar fasciitis may
      become recalcitrant to conservative treatments such as ice, rest, and anti
      inflammatory medication. Exercise-based therapies have received only limited
      attention in the literature for this common problem, yet they are becoming
      increasingly validated for pain relief and positive tissue remodeling at other
      sites of similar soft-tissue overuse injury. This study reports on pain outcomes
      in individuals experiencing chronic plantar fasciitis while wearing a shoe with
      an ultraflexible midsole (Nike Free 5.0) (FREE) versus a conventional training
      (CON) shoe in a 12-week multielement exercise regimen, and after a 6-month follow
      up. Adults with >or= 6-month history of painful heel pain were recruited and
      randomly assigned to wear 1 of the 2 shoes. All subjects completed the same
      exercise protocol. A visual analogue scale item tracked peak pain in the
      preceding 24 hours taken at baseline, 6- and 12-week points, and at the 6-month
      follow-up. Twenty-one subjects completed the program (9 FREE; 12 CON). Both
      groups reported significant improvements in pain by the 6-month follow-up, and
      the FREE group reported an overall reduced level of pain throughout the study as
      a result of lower mean pain scores at the midpoint and post-test compared with
      the CON group. The exercise regimen employed in this study appears to reduce pain
      associated with chronic plantar fasciitis, and in doing so, the Nike 5.0 shoe may
      result in reductions in pain earlier than conventional running shoes.

PMID- 20048544
TI  - Review of exercise and the risk of benign prostatic hyperplasia.
AB  - It has been long appreciated that a healthy lifestyle plays a critical role in
      cardiovascular health. It is now apparent that the same is true in the
      development of benign prostatic hyperplasia (BPH) and lower urinary tract
      symptoms (LUTS). Since 1995, 14 studies have been identified that investigate the
      clinical relationship between exercise and BPH/LUTS. No randomized controlled
      trials have been performed, but useful prospective cohort data originating from
      recent publications on the medical treatment of BPH and prevention of prostate
      cancer are available. Most of the literature supports a clinically significant,
      independent, and strong inverse relationship between exercise and the development
      of BPH/LUTS. Several mechanisms for this relationship have been proposed,
      including decreased sympathetic tone, avoidance of metabolic syndrome, and
      reduced oxidative damage to the prostate.

PMID- 20048545
TI  - Exercise performance by hemodialysis patients: a review of the literature.
AB  - Hemodialysis (HD) patients exhibit poor functional capacity and reduced quality
      of life as a result of the complications associated with end-stage renal disease
      (ESRD). A review of the literature indicates that regular physical activity can
      reduce the complications associated with ESRD by inducing adaptations in the
      cardiovascular, nervous, and musculoskeletal systems. In turn, this increases
      functional capacity and enhances quality of life in patients on HD. Hemodialysis
      patients can safely participate in a variety of exercise programs with minimal
      adverse effects. Intradialytic exercise programs that can incorporate aerobic and
      resistance exercise promote exercise adherence and should be encouraged on
      dialysis units.

PMID- 20048546
TI  - The effects of caffeine on ventilation and pulmonary function during exercise: an
      often-overlooked response.
AB  - The effects of caffeine on exercise performance have been well documented, with
      most reviews focusing on the metabolic, hormonal, and/or central nervous system
      effects. However, caffeine's effects on ventilation and pulmonary function are
      often overlooked. Studies have shown that caffeine is a strong ventilatory
      stimulant, increasing the sensitivity of the peripheral chemoreceptors in
      untrained subjects and increasing exercise ventilation at all workloads in highly
      trained endurance athletes. The consequences of increased exercise ventilation
      could hold either positive or negative effects for exercise performance. Anti
      inflammatory and bronchoprotective effects of caffeine are great enough to
      consider its efficacy as a possible prophylactic antiasthma treatment. Although
      an upper urinary concentration limit exists for caffeine with international
      sports doping control agencies, caffeine's universal accessibility in the
      marketplace has resulted in its daily use being increasingly more socially
      acceptable as an ergogenic substance for sport and exercise.

PMID- 20048547
TI  - An overview of seasonal affective disorder and its treatment options.
AB  - Seasonal affective disorder (SAD) is defined as a history of major depressive
      episodes that recur regularly at a particular time of year. Depending on the
      diagnostic instruments and criteria available, the reported prevalence (1%-10%)
      varies. Neurotransmitter abnormalities have been implicated in the
      pathophysiology, but they do not necessarily explain the seasonal pattern or the
      known chronobiological abnormalities in SAD compared with nonseasonal depression.
      Circadian rhythm abnormalies have been hypothesized to account for these aspects
      of SAD, and they provide a rationale for the therapeutic use of light therapy.
      Family history, twin, and molecular genetics studies suggest that hereditary
      factors are also involved. Light therapy and antidepressant medication are
      effective treatment options, with limited evidence for the efficacy of
      psychotherapy. Some studies demonstrate that narrow-band short wavelength "blue"
      light, naturalistic dawn simulation, and high-density negative air ionization are
      effective. Patients should be informed of the benefits of diet and exercise.
      Light therapy should be clinically monitored in the same manner, as it is done
      for other antidepressant treatments.

PMID- 20048548
TI  - Interplay of oxidants and antioxidants during exercise: implications for muscle
      health.
AB  - Muscle contraction results in generation of reactive oxygen and nitrogen species
      (RONS) at a rate determined by the intensity, frequency, and duration of the
      exercise protocols. Strenuous exercise causes oxidation of protein, lipid, and
      DNA, release of cytosolic enzymes, and other signs of cell damage; however, only
      exhaustive exercise is detrimental. Indeed, the regulation of vascular tone, the
      excitation-contraction coupling, growth, and differentiation in skeletal muscle,
      are governed in part by RONS. This is accomplished by RONS interaction with redox
      sensitive transcription factors, leading to increased gene expression of
      antioxidant enzymes, cytoprotective proteins, and other enzymes involved in
      muscle metabolic functions. However, high levels of RONS generation are known to
      cause oxidative stress, activate certain pathogenic pathways, and accelerate
      aging. This article reviews research from the past decades on the interplay of
      oxidants and antioxidants in skeletal muscle, with particular reference to
      increased contractile activity. Adaptation of muscle to increased oxidative
      stress and the potential mechanisms involved will be highlighted. The role of
      redox-controlled cell signaling in skeletal muscle health and function is also
      described.

PMID- 20048549
TI  - Exercise causing thrombosis.
AB  - Thrombophilia refers to the increased tendency to form blood clots (thrombosis),
      which is a major cause of morbidity and mortality. Thrombosis is associated with
      various chronic conditions such as cancer, diabetes, renal disorders, and
      cardiovascular disease. The incidence and associated complications of thrombosis
      are likely to increase significantly in the next few decades because of aging
      populations. Regular exercise has been proposed to decrease the risk of
      developing thrombosis, although there are inconsistent data from studies
      investigating its effects, with reports of both increased and decreased
      thrombotic risk across a variety of subject cohorts. Confounders such as age,
      gender, hormonal variations, physical activity, underlying disease and treatment,
      and body composition also contribute to the difficulty in assessing and defining
      the precise effects of exercise in preventing thrombotic events. However, there
      is evidence suggesting that physical activity is beneficial for reducing
      thrombotic risk in younger individuals and those with chronic conditions. This
      article aims to summarize the known risk factors for thrombosis and briefly
      review the benefits of exercise in the general population. Furthermore, this
      article highlights the additional factors in a cohort of individuals that would
      (at first) appear unlikely to be at risk of thrombosis--elite athletes.

PMID- 20048550
TI  - Anabolic steroid abuse and dependence in clinical practice.
AB  - The nonmedical use of anabolic-androgenic steroids (AAS) appeals to athletes
      across several sports, particularly those whose activity makes muscle size and
      strength advantageous, and in individuals (usually men) with body dysmorphic
      disorder. Patterns of nonmedical use, including supratherapeutic doses of
      illicitly obtained drugs, increase the risk for adverse psychiatric and other
      medical consequences. Although AAS users may be more likely to consult physicians
      for nonpsychiatric medical consequences than changes in their mental status, it
      is argued that the motivation for persistent use despite adverse consequences is
      sustained in large part by psychological variables. Therefore, all physicians who
      treat nonmedical AAS users will benefit from an understanding of these
      psychological variables, including the potential for AAS to cause dependence.
      This article aims to aid such understanding, and guidelines are suggested for
      assessment and treatment of nonmedical AAS users.

PMID- 20048551
TI  - Benign prostatic hyperplasia: does lifestyle play a role?
AB  - Benign prostatic hyperplasia (BPH) is a very common condition in older men,
      affecting up to 80% of men aged >or= 80 years in the United States. It typically
      leads to lower urinary tract symptoms, which often require medical management.
      The exact cause of BPH is unknown, and the only 2 established factors associated
      with BPH are age and the presence of androgens. Although the presence of
      testosterone is required for the development of BPH, testosterone is not thought
      to be the underlying factor causing BPH because testosterone levels decrease in
      older men. Recent studies have reported that BPH is associated with elevations in
      plasma estradiol/testosterone ratio, insulin, and insulin-like growth factor-I.
      Daily aerobic exercise can reduce all of these plasma factors, particularly when
      combined with a low-fat, high-fiber diet consisting of whole grains, fruits, and
      vegetables. In cell culture studies, this type of lifestyle regimen has recently
      been shown to reduce the growth of serum-stimulated prostate epithelial cells and
      the growth of androgen-dependent prostate cancer cell lines.

PMID- 20048553
TI  - Exercise capacity: a crystal ball in forecasting future health outcomes?
AB  - Although regular physical activity plays an important role in promoting
      cardiovascular health, Williams(1) reported that a high level of
      cardiorespiratory fitness (aerobic capacity) markedly reduces one's risk of
      cardiovascular disease, and the reduction is greater compared with merely being
      physically active (Figure 1). Moreover, there appears to be an inverse
      relationship between cardiorespiratory fitness and complications after bariatric
      surgery among morbidly obese adults. Other provocative data support the
      hypothesis that aerobic capacity, expressed as milliliters of oxygen per kilogram
      of body weight per minute (mL O2/kg/min) or as metabolic equivalents (METs; 1 MET
      3.5 mL O2/kg/min), is inversely associated with health care costs. Collectively,
      these findings and other recent reports suggest that the estimation or direct
      measurement of aerobic capacity can provide independent and additive data in
      forecasting future health outcomes.

PMID- 20048552
TI  - Spontaneous pneumomediastinum and epidural pneumatosis in an adolescent
      precipitated by weight lifting: a case report and review.
AB  - Spontaneous pneumomediastinum is an uncommon condition in athletes. The most
      common cause of spontaneous pneumomediastinum is alveolar rupture into the
      bronchovascular sheath as a result of increased intrathoracic pressure. Epidural
      pneumatosis (pneumorrhachis) has been rarely associated with spontaneous
      pneumomediastinum. In this article, we describe a case of a 17-year-old male who
      presented with neck and chest pain that started 14 hours after a weight lifting
      session. He developed both a pneumomediastinum and epidural pneumatosis--an
      association that is rarely reported in a setting without trauma. To our
      knowledge, there have been only 5 case reports of pneumomediastinum precipitated
      by weight lifting. Improper breathing technique during weight lifting can
      increase the intrathoracic pressure and the risk of pneumomediastinum; hence, it
      is important that physicians and trainers who work with athletes provide
      instructions regarding proper breathing techniques during weight lifting. In
      addition to the case discussion, this article reviews spontaneous
      pneumomediastinum and epidural pneumatosis.

PMID- 20048554
TI  - Does the coingestion of carbohydrate and amino acids improve recovery from
      endurance exercise?
AB  - Practice Pearl: This study demonstrates the importance of protein/amino acids for
      recovery in endurance athletes. Original Article: Skillen RA, Testa M, Applegate
      EA, Heiden EA, Fascetti AJ, Casazza GA. Effects of an amino acid-carbohydrate
      drink on exercise performance after consecutive-day exercise bouts. Int J Sport
      Nutr Exerc Metab. 2008;18(5):473-492.

PMID- 20048555
TI  - Treating hypertriglyceridemia with prescription omega-3 fatty acid ethyl esters.
AB  - Practice Pearl: Clinical trials in patients with very high triglycerides show
      that four 1-g capsules of prescription omega-3 ethyl ester fatty acids taken
      daily can significantly decrease triglyceride levels and are well tolerated.
      Original Article: Sadovsky R, Kris-Etherton P. Prescription omega-3-acid ethyl
      esters for the treatment of very high triglycerides. Postgrad Med.
      2009;121(4):145-150.

PMID- 20048556
TI  - [Androgen replacement therapy improves health-related quality of life in late
      onset hypogonadism patients].
AB  - We examined the effects of androgen replacement therapy (ART) on scores of a
      comprehensive health-related quality of life (HR-QOL) scale (SF-36) in late onset
      hypogonadism (LOH) patients. We received answer sheets on SF-36 from 112 men aged
      37 to 75 years (mean 56.2) who underwent ART between September 2002 and June
      2007. The serum free testosterone levels before ART was 7.32+/-2.09 pg/ml. 250 mg
      of testosterone enanthate was injected intra-muscularly once per 3-4 weeks for 3
      months. When ART was effective to improve the symptoms, it was continued for a
      total of 6 months and was stopped. We evaluated the changes in score on SF-36
      between pre-treatment and 3, 6, and 9 months after initiation of treatment.
      Although prior to ART all subcategory scores on SF-36 were lower than those for
      age-matched healthy Japanese men, each was significantly improved after beginning
      of ART, especially that for the role-emotional (RE), social functioning (SF),
      mental health (MH) and vitality (VT) subscales. No significant difference was
      noted between 3 months after initiation of treatment and 6 or 9 months (3 months
      after stopping ART) in any subcategory score. ART for LOH patients was effective
      not only in curing symptoms but also in improving HR-QOL. The effects of ART
      presented in early periods of treatments and were maintained at least 3 months
      after stopping the treatment.

PMID- 20048557
TI  - [IgG4-related idiopathic retroperitoneal fibrosis: a case report].
AB  - A 75-year-old man visited our hospital with the complaint of lumbago due to
      bilateral hydronephrosis. Computed tomographic (CT) scan revealed a thick and
      homogeneous retroperitoneal soft-tissue mass with isodensity to the muscle, which
      extended from around the kidneys to the bladder. His serum IgG4 level was
      extremely high. He also had proptosis. He was diagnosed as having retroperitoneal
      fibrosis due to IgG4- related sclerosing disease, and treated with glucocorticoid
      and azathioprine. After 2 months, partial regression of the mass was observed.

PMID- 20048558
TI  - [A case of pheochromocytoma associated with neurofibromatosis type 1].
AB  - Pheochromocytoma occurs in 0.1 to 5.7% of patients with type 1 neurofibromatosis
      (NF1). Radiological findings of pheochromocytoma are often similar to those of
      neurofibroma; therefore, any pheochromocytoma should be excised in hypertensive
      patients with NF1. A 60-year-old male patient with NF1 was referred to this
      hospital for an incidentally discovered right adrenal mass, 7 x 6 mm in diameter.
      The patient had multiple benign tumors and suffered from hypertension for 4
      years. Laboratory findings showed increased serum and urine catecholamine levels.
      Magnetic resonance imaging (MRI) revealed a high signal intensity on T2-weighted
      images, which was enhanced by gadolinium contrast. The mass was positive for 131
      I-metaiodobenzylguanidine (MIBG) scintigraphy. A laparoscopic adrenalectomy was
      performed. A histopathological diagnosis of pheochromocytoma was made. The
      patient's post-operative course was uneventful, and blood pressure was
      normalized. Screening of the adrenal tumor is strongly recommended for NF1
      patients with hypertension, since any unfavorable events due to catecholamine
      such as cardiomyopathy and fatal arrhythmia can be avoided by adequate surgical
      intervention.

PMID- 20048559
TI  - [A case of retroperitoneal Mullerian cyst resected laparoscopically].
AB  - A 67-year-old female patient had a cystic mass, 6 cm in diameter, which was
      incidentally detected on the dorsal side of the cecum in the retroperitoneum. A
      laparoscopic tumor excision was performed. Microscopically, the majority of the
      cystic wall consisted of Mullerian type serous epithelium, partially including
      the columnar epithelium containing round nuclei and mucin production. The
      columnar epithelium was similar to the uterocervical epithelium, and there was
      proliferation of dense collagen fibers resembling ovarian stroma under the
      epithelium. These microscopic findings were consistent with ovarian seromucinous
      cystadenoma. Therefore, the cyst was diagnosed to be a retroperitoneal Mullerian
      cyst. This is the 15th case of a cyst of this type reported and is the first case
      in which a laparoscopic excision was performed.

PMID- 20048560
TI  - [Multiple inflammatory pseudotumor of the paranephric fat].
AB  - A 57-year-old man was referred to our hospital because of a paranephric tumor
      detected by preoperative computed tomography (CT) for the ascending colon
      carcinoma. Since the paranephric tumor was small, surgical treatment was
      performed only for the colon carcinoma. The follow-up CT showed increase in size
      and number of paranephric tumor masses. It was suspected to be a soft tissue
      malignant tumor. Left radical nephrectomy was performed. Pathological findings
      revealed inflammatory pseudotumor of the paranephric fat. To our knowledge, this
      is the 4th case with inflammatory pseudotumor of the paranephric fat.

PMID- 20048561
TI  - [A case of leiomyosarcoma in a huge bladder diverticulum].
AB  - A 68-year-old man was admitted to our hospital for investigation of dysuria and
      palpable lower abdominal mass. Computed tomography and magnetic resonance imaging
      demonstrated a huge bladder diverticulum tumor which infiltrated the mesentery
      and abdominal wall with multiple lymph node swelling in the pelvis. The tumor was
      partially resected by a transurethral approach and was histologically diagnosed
      as malignant neoplasm with marked necrosis. The patients underwent partial
      cystectomy with dissection of the mesentery and ileum. Pathological examination
      showed the tumor to be a leiomyosarcoma with mesentery infiltration. The patient
      had local recurrence with pulmonary metastasis two weeks after the operation and
      died 39 days after the operation. This is the third case of leiomyosarcoma of the
      diverticulum of urinary bladder reported in Japan.

PMID- 20048563
TI  - [A case of giant prostate carcinoma difficult to diagnose because of absence of
      urinary difficulty].
AB  - A 76-year-old man who had been suffering from bilateral leg edema and lower
      abdominal distension since June 2008, consulted our hospital. The computed
      tomography revealed a giant pelvic mass with a high value of prostate specific
      antigen. A transrectal prostatic biopsy was performed and the histopathological
      diagnosis was poorly differentiated adenocarcinoma of prostate. The clinical
      stage was D2 with multiple lung metastases but no bone metastasis. After 3 months
      of multiple androgen blockade (MAB), the multiple lung metastases disappeared.
      MAB is being continued.

PMID- 20048562
TI  - [A pheochromocytoma of urinary bladder treated with neoadjuvant chemotherapy].
AB  - A 69-year-old female presented with hypertension and a solid mass in the bladder
      on ultrasonography. Cystoscopy revealed a submucosal tumor in the right lateral
      wall of the bladder. A transurethral resection was performed. Histologically,
      pathologic examination revealed a malignant pheochromocytoma. She refused
      surgical therapy and radiation therapy. She had no treatment for two years. She
      suddenly complained of gross hematuria. T2-weighted magnetic resonance imaging
      showed a bladder tumor of high intensity and extra-bladder invasion. She was
      treated with chemotherapy (CVD) for 26 cycles. Since the tumor size was reduced,
      she was referred to our hospital for operative indication. Partial cystectomy was
      performed. Histologically, the tumor was a pheochromocytoma of the urinary
      bladder. Ten months after the operation, she has no clinical evidence of
      recurrence.

PMID- 20048564
TI  - [Rectourethral fistula after radical retropubic prostatectomy: a case report].
AB  - The patient, a 56-year-old man, had surgery for anal fistula at the age of 28. In
      August 2007, he underwent a radical retropubic prostatectomy (RRP) for prostate
      cancer. Rectal injury was not recognized during the operation. However, on the
      8th postoperative day, fecaluria appeared, and rectourethral fistula was
      diagnosed. We attempted conservative therapy including diverting colostomy and
      continued drainage using a urethral catheter. Subsequently, the fistula closed
      spontaneously 3 months after RRP. Eight months after RRP, we performed a
      transanal repair of rectal mucosa based on the rectal wall advancement flap
      procedure. The postoperative course was uneventful, and the colostomy was closed
      in July 2008. By April 2009, he had normal voiding and full anal continence
      without fistula recurrence.

PMID- 20048565
TI  - [Testicular Leydig cell tumor presenting as male infertility: a case report].
AB  - A Leydig cell tumor is a rare disease entity occurring in the testis.
      Occasionally it is considered to be related to male infertility. We report a case
      study of a Leydig cell tumor in a single testis presenting as male infertility. A
      38-year-old male was referred to our hospital because of a tumor in his right
      testis. He had undergone left orchiectomy at one year old because of a testicular
      tumor. During an examination related to the infertility, ultrasound revealed a 1
      cm tumor. Tumor markers were all within normal ranges.Hormonal examination showed
      that luteinizing hormone (LH) 30.3 mIU/ml (1.5-12.4) and follicle stimulating
      hormone (FSH) 11.9 mIU/ml (1.7-8.6) were higher than normal limits, but total
      testosterone(total T) and estradiol (E2) were within normal ranges. Tumor
      enucleation was first performed, and then testicular sperm extraction (TESE) was
      carried out from a macroscopically normal site of the testis.Histopathological
      diagnosis was a benign Leydig cell tumor surrounded by Leydig cell hyperplasia.
      For 12 months after the operation there has been no recurrence. Although high LH
      and FSH persisted, total T and E2 were within normal ranges.

PMID- 20048566
TI  - [Torsion of a testicular cancer in cryptorchidism prolapsing out of the inguinal
      canal: a case report].
AB  - A 47-year-old man visited our hospital suffering from intensive pain of the
      swelling mass in his left inguinal region. He had never recognized the left
      testis in his scrotum, and felt the left inguinal mass growing slowly since a
      year ago. Computed tomography and Doppler uitrasonography revealed a mass
      approximately 5 cm in diameter separating from intestines in the abdominal cavity
      and not supplied sufficient blood flow. We suspected that the mass was a
      testicular cancer in cryptorchidism with testicular torsion and performed
      orchiectomy. At the time of the operation, the mass and the spermatic cord were
      twisted and prolapsed out of the aponeurosis of external abdominal oblique
      muscle. Histopathologically, malignant degeneration was demonstrated in the
      undescended testis, and the cell type was seminoma. We definitely diagnosed the
      mass as torsion of a testicular cancer in cryptorchidism prolapsing out of the
      inguinal canal.

PMID- 20048572
TI  - Simple two-stage reconstructive technique for the treatment of infected dura
      mater.

PMID- 20048573
TI  - Various Z-plasty designs for the treatment of columellar scar in rhinoplasty.

PMID- 20048574
TI  - Discussion. Outcomes and patient satisfaction following breast reconstruction
      with bilateral pedicled TRAM flaps in 105 consecutive patients.

PMID- 20048575
TI  - Postburn philtrum and upper lip reconstruction.

PMID- 20048576
TI  - Fat grafting in postmastectomy breast reconstruction with expanders and
      prostheses in patients who have received radiotherapy: formation of new
      subcutaneous tissue.
AB  - BACKGROUND: In secondary mammary reconstruction in irradiated patients, the use
      of expanders and prostheses is controversial, given that radiotherapy increases
      tissue fibrosis and capsular contracture. The authors assessed the usefulness of
      tissue expansion, prostheses, and fat grafting in patients who had received
      radiotherapy. METHODS: The authors conducted a study of 65 mastectomized patients
      (age range, 34 to 62 years) who had received radiotherapy with a 6-MeV electron
      accelerator. In the first operation, they inserted the Natrelle 133-MV expander
      (Allergan, Inc., Irvine, Calif.) endoscopically under the pectoralis major at the
      end of the mastectomy scar and performed total immediate expansion. The authors
      injected a mean quantity of 150 +/- 25 cc of fat in the upper quadrants between
      the skin and the muscle and also inside the muscle. After 3 months, they removed
      the expander through the same incision, inserted the McGhan Style 410 cohesive
      silicone prosthesis, and injected a mean 150 +/- 30 cc of fat in the lower
      quadrants. In the third stage, the nipple-areola complex was reconstructed.
      RESULTS: Mean follow-up was 1 year, with controls after 1 week, 1 month, 3
      months, and 12 months. No complications were recorded with the fat injections.
      Patients' mean satisfaction rating was 4 on a scale of 1 (low) to 5 (high), and
      the capsular contracture was never above 1 on the Baker classification.
      CONCLUSION: In mastectomized patients who received radiotherapy, fat grafting in
      addition to traditional tissue expander and implant breast reconstruction
      achieves better reconstructive outcomes with the creation of new subcutaneous
      tissue, accompanied by improved skin quality of the reconstructed breast without
      capsular contracture.

PMID- 20048577
TI  - Use of an arteriovenous fistula in facial reanimation after cystic hygroma
      resection.

PMID- 20048578
TI  - Management of chronic seroma following latissimus dorsi breast reconstruction: a
      new technique.

PMID- 20048579
TI  - Nipple reconstruction on implant-only breast mounds: the use of a delay.

PMID- 20048580
TI  - Increasing the versatility of the latissimus dorsi skin paddle in breast
      reconstruction.

PMID- 20048581
TI  - Magnetic resonance imaging-based breast volumetry in breast surgery: a transfer
      from neurosurgery.

PMID- 20048582
TI  - Breast reconstruction and lymphedema.
AB  - BACKGROUND: The authors conducted this study to determine the following: Does
      delayed breast reconstruction that requires surgical dissection in the previously
      operated on and/or irradiated axilla lead to a higher incidence of lymphedema? In
      patients who have developed lymphedema following mastectomy, does delayed breast
      reconstruction with autologous flap reduce the severity of the lymphedema?
      METHODS: Four hundred eighty-two consecutive delayed autologous breast
      reconstructions performed at the authors' institution were evaluated. The authors
      evaluated the effects of flap choice, recipient vessel choice, previous
      radiotherapy, and previous axillary node dissection on lymphedema development
      after breast reconstruction. The authors also evaluated the effect of autologous
      breast reconstruction on the status of the preexisting lymphedema. RESULTS: Four
      hundred forty-four delayed breast reconstructions were performed using 394 free
      flaps and 50 latissimus dorsi flaps in patients with no lymphedema. Lymphedema
      developed in 16 cases (3.6 percent). The type of flap, the site of recipient
      vessel, previous radiotherapy, and previous axillary node dissection did not have
      a significant effect on the incidence of lymphedema after breast reconstruction.
      Breast reconstructions were performed in 38 patients who already had lymphedema:
      nine (23.7 percent) demonstrated significant improvement, and none demonstrated
      worsening of lymphedema after breast reconstruction. CONCLUSIONS: The incidence
      of lymphedema following delayed autologous breast reconstruction is low, and the
      use of thoracodorsal vessels or a latissimus dorsi flap, even in patients with
      previous axillary node dissection or irradiation, was not associated with a
      significantly higher risk of developing lymphedema. In patients who developed
      lymphedema following mastectomy, delayed autologous breast reconstruction may
      help reduce the severity of lymphedema.

PMID- 20048583
TI  - Salvage of an infected and exposed breast device with implant retention and
      delayed exchange.

PMID- 20048584
TI  - Malignant skin tumor in a composite tissue (bilateral hand) allograft recipient.

PMID- 20048585
TI  - Flexor pollicis longus tendon rupture after volar plating of a distal radius
      fracture.

PMID- 20048586
TI  - Long-term survival with decreased morbidity in the treatment of a malignant
      peripheral nerve sheath tumor.

PMID- 20048587
TI  - Computed tomographic angiography with VirSSPA three-dimensional software for
      perforator navigation improves perioperative outcomes in DIEP flap breast
      reconstruction.
AB  - BACKGROUND: Vascular anatomy of the abdominal wall varies greatly, especially in
      the case of the perforator branches of the deep inferior epigastric artery.
      Preoperative three-dimensional reconstructions with VirSSPA software have been
      used in the authors' center since the year 2007 for the planning of perforator
      flaps in breast reconstruction. The main objectives were to reduce surgery time
      and the number of complications. METHODS: A comparative study was conducted in 70
      patients subjected to delayed breast reconstruction based on unilateral deep
      inferior epigastric perforator (DIEP) flaps. Half of the patient group underwent
      preoperative imaging with computed tomographic angiography-guided VirSSPA
      reconstruction, whereas the other half was subjected to preoperative Doppler
      ultrasound for perforator mapping. Operation time ranges, lengths of stay, and
      operative complications were assessed. RESULTS: The use of VirSSPA preoperative
      planning correlated with operative times reduced by a mean of 2 hours 8 minutes.
      In addition, a statistically significant reduction (>45 percent) in the incidence
      of any flap-related complications was observed in patients undergoing
      preoperative computed tomographic angiography-guided VirSSPA reconstruction and a
      decrease above 50 percent in overall donor-site morbidity. The use of computed
      tomographic angiography-guided VirSSPA three-dimensional reconstruction was found
      to be a protective factor against developing any kind of complication after DIEP
      flap surgery (odds ratio, 0.03; 95 percent confidence interval, 0.006 to 0.15).
      CONCLUSIONS: Computed tomographic angiography-guided VirSSPA three-dimensional
      reconstruction in the assessment of perforator flaps was proved to be safe and
      reliable. The main benefits of this technique were the reduction of surgical time
      and reduction of the number of complications.

PMID- 20048588
TI  - Acute dorsal radiocarpal dislocation associated with scapholunate ligament
      avulsion: a proposal for surgical treatment.

PMID- 20048589
TI  - Liebenberg syndrome: first case of monovular twins.

PMID- 20048590
TI  - Do waistline and umbilical position really change after abdominoplasty?

PMID- 20048591
TI  - Medial thigh fasciocutaneous flaps for reconstruction of the scrotum following
      Fournier gangrene.

PMID- 20048592
TI  - A note of caution on the use of the distally based anterolateral thigh flap:
      anatomical evidence.

PMID- 20048593
TI  - Bilateral sciatic neurapraxia following combined abdominoplasty and mastopexy.

PMID- 20048594
TI  - Breast reduction in gigantomastia using the posterosuperior pedicle: an
      alternative technique, based on preservation of the anterior intercostal artery
      perforators.
AB  - BACKGROUND: The purpose of this study was to describe and evaluate the outcomes
      of breast reduction in cases of gigantomastia using a posterosuperior pedicle.
      METHODS: Four hundred thirty-one breast reductions were performed between 2004
      and 2007. Fifty patients of 431 (11.6 percent) responded to the inclusion
      criteria (>1000 g of tissue removed per breast (100 breasts). The mean age was
      33.2 years (range, 17 to 58 years). The average notch-to-nipple distance was 37.9
      cm (range, 35 to 46 cm). The mean body mass index was 27 (range, 22 to 35 cm).
      The technique of the posterosuperior pedicle was used, in which the perforators
      from fourth anterior intercostal arteries are preserved (posterior pedicle).
      Results were evaluated by means of self-evaluation at 1 year postoperatively.
      RESULTS: The average weight resected was 1231 g (range, 1000 to 2500 g). The
      length of hospital stay was 2.3 days (range 2 to 4 days). Thirty seven patients
      evaluated their results as "very good" (74 percent), nine as "good" (18 percent),
      and four as "acceptable" (8 percent). There were no "poor" results. The chief
      complaint was insufficient breast reduction (four patients), despite the
      considerable improvement in their daily life (8 percent). Back pain totally
      resolved in 46 percent and partially (with significant improvement) in 54 percent
      of cases. One major and seven minor complications were recorded. CONCLUSIONS: The
      posterosuperior pedicle for breast reduction is a reproducible and versatile
      technique. The preservation of the anterior intercostal artery perforators
      enhances the reliability of the vascular supply to the superior pedicle.

PMID- 20048595
TI  - Influence of foot height on tissue oxygenation of diabetic feet.

PMID- 20048596
TI  - Choosing a residency program.

PMID- 20048597
TI  - New system of collecting fat with a bottle of Redon drainage.

PMID- 20048598
TI  - Chronic headaches/migraines: extending indications for breast reduction.
AB  - BACKGROUND: In patients with macromastia, the currently accepted indications for
      reduction mammaplasty are back pain, neck pain, shoulder grooving, and intertrigo
      in the inframammary fold. Occipital neuralgia and chronic headaches/migraines are
      not indications, but the authors noted anecdotally that numerous patients with
      macromastia complained of chronic headaches/migraines, and many of them reported
      headache improvement following surgery. Therefore, the authors conducted a
      retrospective review of their cases to evaluate this association. METHODS: A
      retrospective chart review of all patients undergoing reduction mammaplasty
      between 2003 and 2008 performed by the senior author (I.D.) was conducted.
      Patients were followed with clinic visits and telephone interviews. Collected
      data included preoperative symptoms, pain scores, and postoperative findings.
      Statistical analysis was conducted using the paired t test. RESULTS: Of the 84
      patients who underwent reduction mammaplasty for macromastia between 2003 and
      2008, 58 (69 percent) had chronic headaches preoperatively. Of these 58 patients,
      31 (53 percent) reported a greater than 50 percent reduction in headache
      frequency and severity, with 12 (21 percent) stating that their headaches
      resolved completely after surgery. These patients reported a mean pain score of
      7.2 (of 10) before surgery that dropped to 3.2 after reduction mammaplasty. Of
      all patients, 90 percent reported an improvement in their quality of life.
      CONCLUSIONS: The authors' data show that patients with macromastia who have
      occipital neuralgia and/or chronic headaches/migraines can experience headache
      relief following reduction mammaplasty. Future research should evaluate headaches
      as indications for reduction mammaplasty. Those patients whose headaches do not
      improve following breast reduction should consider further specialized evaluation
      and treatment.

PMID- 20048599
TI  - The deep inferior epigastric perforator flap: myth and reality.

PMID- 20048600
TI  - Breast tissue expander device volume: should it be a factor?

PMID- 20048601
TI  - Human tissue-resident stem cells combined with hyaluronic acid gel provide
      fibrovascular-integrated soft-tissue augmentation in a murine photoaged skin
      model.
AB  - BACKGROUND: Transplantation of adipose tissue-resident mesenchymal stem cells has
      been found to contribute to the establishment of a supportive fibrovascular
      network. The authors sought to evaluate the potential of human adipose tissue
      derived stem cells to integrate with nonanimal stabilized hyaluronic acid as a
      novel injectable soft-tissue filler. METHODS: Cell proliferation was measured by
      bromodeoxyuridine incorporation. Interactions of adipose tissue-derived stem
      cells with hyaluronic acid were documented by scanning electron microscopy. The
      effect of this combination on procollagen mRNA was assessed by real-time
      polymerase chain reaction. The potential therapeutic effects were evaluated in an
      athymic murine photoaged skin model by histology and by high-resolution magnetic
      resonance imaging. Angiogenesis was assessed by microvessel density analysis.
      RESULTS: Under in vitro culture conditions, the authors found an equal
      proliferation capacity of adipose tissue-derived stem cells grown on hyaluronic
      acid versus controls. Scanning electron microscopy showed enhanced establishment
      of complex microvillous networks in adipose tissue-derived stem cells adherent to
      hyaluronic acid compared with controls. Adipose tissue-derived stem cells and
      hyaluronic acid induced a significant increase in procollagen 1-alpha-2 mRNA
      expression compared with controls. In an athymic murine photoaged skin model,
      injection of this combination ablated photoinduced skin wrinkles. Magnetic
      resonance imaging revealed a consistent and stable volume fill by adipose tissue
      derived stem cells and nonanimal stabilized hyaluronic acid at 3 weeks. Adipose
      tissue-derived stem cells actively incorporated into the hyaluronic acid fill and
      showed an organized fibrovascular network at 3 weeks. CONCLUSION: The combination
      of adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid
      holds promise as a tool with which to achieve lasting volume fill in
      reconstructive surgical soft-tissue augmentation.

PMID- 20048602
TI  - Interaction of wingless protein (Wnt), transforming growth factor-beta1, and
      hyaluronan production in fetal and postnatal fibroblasts.
AB  - BACKGROUND: Mammalian fetal skin injury heals scarlessly. The intrinsic
      differences between embryonic and adult fibroblasts that underlie this
      observation are poorly understood. Several studies have linked Wnt proteins with
      skin morphogenesis. The authors' study aimed to establish a correlation between
      beta-catenin-dependent (canonical) Wnt protein, transforming growth factor (TGF)
      beta1, and the expression of hyaluronan synthesis enzymes during scarless versus
      scarring wound healing. METHODS: Wnt signaling was quantified after 1.5-mm skin
      wounds were created in BAT-gal fetal (e16.5) and postnatal (p1) mice. Canonical
      Wnt signals were localized by X-gal staining and quantified with quantitative
      real-time polymerase chain reaction. Primary embryonic and postnatal mouse dermal
      fibroblasts were treated with recombinant Wnt3a or TGF-beta1. Proliferation was
      assayed by bromodeoxyuridine incorporation. Gene expression of enzymes that
      regulate hyaluronan production and turnover was examined by quantitative real
      time polymerase chain reaction (hyaluronan synthases or HAS1-3, hyaluronadase-2),
      as well as other target genes for Wnt and TGF-beta (Axin2, TGF-beta1, TGF-beta3,
      type 1 collagen, proliferating cell nuclear antigen). RESULTS: Canonical Wnt
      signaling increased following wounding in postnatal, but not fetal, mice. In
      vitro, rmWnt3a increased postnatal fibroblast proliferation but not in embryonic
      cells. Both Wnt3a and TGF-beta1 induced HAS2 and HAS3 gene expression in
      embryonic fibroblasts, while HAS1 and Hyal2 were induced in postnatal
      fibroblasts. Finally, rmWnt3a significantly increased type I collagen expression,
      particularly in postnatal fibroblasts, and influenced expression of TGF-beta
      isoforms. CONCLUSIONS: Increased canonical Wnt signaling occurs during postnatal
      but not fetal cutaneous wound repair. Fetal and postnatal fibroblasts have a
      disparate response to rmWnt3a in vitro. rmWnt3a affects postnatal fibroblasts in
      a similar fashion to rhTGF-beta1, a known profibrotic cytokine.

PMID- 20048603
TI  - The effect of epidural anesthesia on muscle flap tolerance to venous ischemia.
AB  - BACKGROUND: Venous ischemia is a major cause of failure after free tissue
      transfers and replantations. The combination of general and epidural anesthesia
      leads to vasodilatation and improves tissue perfusion. Postoperative pain relief
      and sympathetic blockage are additional benefits of epidural anesthesia. The
      purpose of this study was to determine whether epidural anesthesia has benefits
      on microcirculation and neutrophil functions in muscle flaps subjected to venous
      ischemia. METHOD: Thirty Sprague-Dawley rats were divided into three groups:
      group I, general anesthesia; group II, spinal anesthesia; and group III, epidural
      anesthesia. Cremaster flaps were prepared, postcapillary venules were selected
      under intravital videomicroscopy, and flaps were subjected to venous ischemia.
      Images were recorded from preselected postcapillary venules before venous
      ischemia (baseline) and following reperfusion. Neutrophil rolling and adhesion,
      functional capillary density, and diameters of postcapillary venules were
      evaluated. RESULTS: The increase in rolling neutrophils in group III was
      significantly lower than in groups I and II at 60 and 120 minutes. Change of
      adherent neutrophils in group III was significantly lower than in groups I and II
      at 15, 60 and 120 minutes. There was significantly more reduction in inner
      diameter of postcapillary venules in groups I and II compared with group III.
      Functional capillary density in groups I and II was significantly lower than in
      group III. CONCLUSION: Epidural anesthesia regulated neutrophil functions,
      salvaged functional capillaries, and prevented vasoconstriction of postcapillary
      venules in cremaster muscle flaps subjected to venous ischemia. Spinal and
      general anesthesia, however, were found to be ineffective in improving
      microcirculation of muscle flaps subjected to venous ischemia.

PMID- 20048605
TI  - Discussion. First U.S. near-total human face transplantation: a paradigm shift
      for massive complex injuries.

PMID- 20048604
TI  - Rodent facial nerve recovery after selected lesions and repair techniques.
AB  - BACKGROUND: Measuring rodent facial movements is a reliable method for studying
      recovery from facial nerve manipulation and for examining the behavioral
      correlates of aberrant regeneration. The authors quantitatively compared recovery
      of vibrissal and ocular function following three types of clinically relevant
      nerve injury. METHODS: One hundred seventy-eight adult rats underwent facial
      nerve manipulation and testing. In the experimental groups, the left facial nerve
      was either crushed, transected, and repaired epineurially, or transected and the
      stumps suture-secured into a tube with a 2-mm gap between them. Facial recovery
      was measured for the ensuing 1 to 4 months. Data were analyzed for whisking
      recovery. Previously developed markers of co-contraction of the upper and
      midfacial zones (possible synkinesis markers) were also examined. RESULTS:
      Animals in the crush groups recovered nearly normal whisking parameters within 25
      days. The distal branch crush group showed improved recovery over the main trunk
      crush group for several days during early recovery. By week 9, the
      transection/repair groups showed evidence of recovery that trended further upward
      throughout the study period. The entubulation groups followed a similar recovery
      pattern, although they did not maintain significant recovery levels by the study
      conclusion. Markers of potential synkinesis increased in selected groups
      following facial nerve injury. CONCLUSIONS: Rodent vibrissal function recovers in
      a predictable fashion following manipulation. Generalized co-contraction of the
      upper and midfacial zones emerges following facial nerve manipulation, possibly
      related to aberrant regeneration, polyterminal axons, or hypersensitivity of the
      rodent to sensory stimuli following nerve manipulation.

PMID- 20048606
TI  - Treatment of earlobe keloids by extralesional excision combined with preoperative
      and postoperative "sandwich" radiotherapy.
AB  - BACKGROUND: Earlobe keloids can form after cosmetic ear piercing, trauma,
      infection, or burns, or spontaneously. These keloids are highly resistant for
      treatment and are followed by severe cosmetic implications. There are various
      surgical and nonsurgical treatment modalities for earlobe keloids, with no
      universally accepted treatment policy and a wide range of reported recurrence
      rates. The authors present their experience of treating earlobe keloids using the
      "sandwich" technique protocol; extralesional excision and external-beam
      radiotherapy are given a day before and a day after the operation. METHODS: The
      authors retrospectively reviewed all patients with earlobe keloids treated by the
      "sandwich" technique between the years 1996 and 2005. Patients were categorized
      into two groups: a high-risk group for previously treated patients and patients
      with a tendency for hypertrophic scars and keloids, and a low-risk group for the
      others. All patients underwent extralesional excision of the keloid and local
      radiotherapy before the excision and following it. Follow-up was a minimum of
      half a year and included a patient satisfaction questionnaire and documentation
      of keloid recurrence or cure. RESULTS: A total of 23 patients were treated by
      this protocol; 57 percent were male. Patients had an average age of 24 years. The
      most common keloid etiology was earlobe piercing. Recurrence rates for the low
      risk and high-risk groups were 25 and 27 percent [percent of the patients],
      respectively. Overall patient satisfaction was high. CONCLUSION: The combined
      excision and "sandwich" radiotherapy technique is a simple and effective method
      for treating earlobe keloids, with high patient satisfaction and low recurrence
      and complication rates.

PMID- 20048607
TI  - Long-term results for the use of gold eyelid load weights in the management of
      facial paralysis.
AB  - BACKGROUND: The placement of gold eyelid load weights to improve passive upper
      eyelid animation is integral to the management of patients with facial palsy,
      particularly for patients with long-term paralysis. METHODS: In a retrospective
      cohort review, outcomes after placement of 104 gold weights in 94 eyelids
      implanted by one surgeon from 1986 to 2000 were evaluated. The primary outcome
      measures were improvement in corneal exposure and visual acuity. Secondary
      outcome measures included time to removal and rates of adverse effects and
      complications. RESULTS: Mean time of follow-up was 43.37 +/- 41.40 months (range,
      1 to 53 months). Visual acuity and corneal compensation improved after weight
      placement (p = 0.0001), while the necessary daily ocular care decreased. Overall,
      91 (97 percent) of the 94 first-time weights implanted were successful in
      providing improved protection for the patient's eye and decreasing the daily care
      needs. Eleven weights (10.6 percent) became exposed and were removed. Kaplan
      Meier survival curve analysis predicted a 3 percent exposure rate at 12 months, 5
      percent at 24 months, and 10 percent at 5 years, which increased to 35 percent at
      153 months. When needed, replacement weights were equally effective in
      maintaining ocular health. CONCLUSIONS: This study demonstrates that gold eyelid
      load weights help preserve vision and improve corneal compensation, while
      minimizing ocular nursing care. The complications are few, but after
      approximately 5 years, the incidence of weight exposure increases to
      approximately 10 percent. The exposure rate continues to increase with longer
      follow-up intervals. Extruded weights can be replaced multiple times with the
      expectation that they will continue to provide a good result.

PMID- 20048608
TI  - Direct tongue neurotization: the effect on speech intelligibility in patients
      with Mobius syndrome.
AB  - BACKGROUND: Mobius syndrome is a disorder characterized by developmental
      impairment of cranial nerve VII, VI, often XII, and other cranial nerves. Facial
      reanimation in such patients restores the ability of some motion and of limited
      emotional expression. In one-fourth of these patients, hypoglossal involvement
      results in severe speech impairment due to tongue atrophy and lack of voluntary
      mobility. Bilabial incompetence due to facial paralysis further deteriorates
      speech capability. Direct tongue neurotization has been used by the senior author
      (J.K.T) to improve tongue function and speech intelligibility in patients with
      Mobius syndrome. This study presents the senior author's experience with the
      technique as a component of multistage facial reanimation procedures. METHODS:
      Data collection was performed by retrospective review on six patients with Mobius
      syndrome who underwent direct tongue neurotization. In addition, each patient was
      videotaped for 30 minutes preoperatively and postoperatively according to a
      standardized protocol. RESULTS: Four independent investigators scored speech
      intelligibility in each patient using a standardized grading system. The results
      showed considerable improvement in speech intelligibility and articulation.
      Higher improvement was noted in patients with partial bilateral hypoglossal
      involvement than in patients with complete unilateral involvement of the
      hypoglossal nerve, as well as in younger ages. No difference was noted between
      sexes. CONCLUSIONS: To the authors' knowledge, this is the first study presenting
      the effect of direct tongue neurotization on speech intelligibility in patients
      with Mobius syndrome. Tongue neurotization has therefore an important role in
      restoring the ability of these patients to communicate and obtain the potential
      to develop normal social skills.

PMID- 20048609
TI  - Circumferential pharyngoesophageal reconstruction with a supraclavicular artery
      island flap.

PMID- 20048610
TI  - Advancements in free flap monitoring in the last decade: a critical review.
AB  - BACKGROUND: The authors conducted a review of the recent literature on the
      monitoring of free flaps to create an overview of the current monitoring devices
      and their potential as an ideal monitoring method. METHODS: A literature-based
      study was conducted using the PubMed and Cochrane databases. The following search
      terms were used: "flap" and "monitoring." All monitoring methods found between
      January of 1999 and January of 2009 were evaluated. Monitoring methods that were
      described in five or more clinical reports were further investigated. RESULTS:
      The advantages and disadvantages of conventional monitoring methods, the
      implantable Doppler system, color duplex sonography, near-infrared spectroscopy,
      microdialysis, and laser Doppler flowmetry are presented. Furthermore, an
      overview is given of their potential as ideal monitoring method. CONCLUSIONS: The
      implantable Doppler system, near-infrared spectroscopy, and laser Doppler
      flowmetry appear to be the best monitoring devices currently available. As most
      of the publications on monitoring have focused on the reliability of the systems,
      future research should also address their cost efficiency.

PMID- 20048611
TI  - Evaluation of a new wound closure device for linear surgical incisions: 3M Steri
      Strip S Surgical Skin Closure versus subcuticular closure.
AB  - BACKGROUND: Technological innovations are often adopted before scientific
      comparison to an accepted standard. The authors' study compared suture with a new
      coaptive film device, 3M Steri-Strip S Surgical Skin Closure, on linear
      incisions. METHODS: Patients undergoing Wise-pattern breast reduction or
      abdominal procedures had paired incisions randomly assigned to Steri-Strip S or
      suture closure. Key outcome measures were closure time, patient comfort, and scar
      quality at 6 months by patients and surgeons using a new scar evaluation tool,
      visual assessment of linear scars. Statistical differences between the two
      closure techniques were assessed by Wilcoxon signed rank test. RESULTS: Of 59
      patients, eight were excluded from randomization (a surgeon judged Steri-Strip S
      to be a nonviable closure technique for mismatched wound edges). Fifty-one
      patients (breast, n = 24; abdomen, n = 27) were randomized. Operative time with
      Steri-Strip S for breast was 2.0 minutes (SD = 1.1) versus suture closure at 4.6
      minutes (SD = 1.5; p < 0.001). Similarly, Steri-Strip S versus suture for the
      abdomen was faster (p < 0.001; 4.9 minutes, SD = 2.3 versus 10.1 minutes, SD =
      3.4). Comfort scores did not differ between closures [5.8 (SD = 2.7) versus 6.9
      (SD = 2.0), respectively, on breast (p = 0.142) and 7.7 (SD = 1.8) versus 7.7 (SD
      = 2.3) on abdomen (p = 0.903)]. Complication rates did not differ between closure
      types. Patients' visual assessment of linear scars rating of breasts was 3.8 (SD
      = 2.9) for Steri-Strip S and better at 2.6 (SD = 2.9) for suture (p = 0.008). One
      surgeon rated breast Steri-Strip S scars worse than suture scars (4.3 versus 3.7;
      p = 0.014). For abdominal scars, there was no difference in the patient or
      surgeon ratings. CONCLUSIONS: Steri-Strip S permits faster wound closure than
      suture. On the basis of patient reports of comfort and scar quality, surgeons
      increase efficiency and maintain quality with the use of Steri-Strip S on
      abdominal wounds but not on breast wounds.

PMID- 20048612
TI  - Fibula free flap reconstruction of the pelvis in children after limb-sparing
      internal hemipelvectomy for bone sarcoma.
AB  - BACKGROUND: Neoadjuvant chemotherapy has improved the treatment of bone sarcomas,
      making wide resection with limb salvage frequently possible. However, resection
      of iliac tumors without reconstruction causes pelvic instability and significant
      leg length discrepancy. Free vascularized bone autograft reconstruction
      represents a potentially optimal method for iliac reconstruction because of the
      faster healing time and rapid hypertrophy of the grafts. Furthermore, living
      incorporated autograft may be more durable in the setting of radiation therapy or
      chemotherapy. The purpose of this study was to characterize the successful
      reconstruction of the pelvis in children using a triangular double-barrel fibula
      free flap following limb-sparing internal hemipelvectomy for sarcoma. METHODS: A
      retrospective review of the operative records and patient charts was performed
      with identification of patient characteristics, operative details, postoperative
      outcomes, complications, and need for additional procedures. RESULTS: Four
      patients were identified who underwent fibula free flap reconstruction of the
      hemipelvis following type I resection with preservation of the hip joint. The
      mean age of the patients was 13.4 years, with a mean follow-up of 7.2 years. Flap
      survival was 100 percent, no postoperative infections occurred, and there were no
      local recurrences. All four patients returned to independent ambulation. The
      female patient was ultimately able to bear two children. One patient required
      epiphysiodesis for leg length discrepancy. CONCLUSIONS: An "A-frame" double
      barrel fibula free flap can be used effectively for reconstruction of the type I
      internal hemipelvectomy defect. It permits a return to ambulation and minimizes
      leg length discrepancy and other complications, which may be critical in the
      immature pediatric skeleton.

PMID- 20048613
TI  - Pedicled perforator flaps: a new principle in reconstructive surgery.
AB  - BACKGROUND: In the evolution of flap physiology and reconstruction, there has
      been a trend of decreased donor-site morbidity. In this article, the chronology
      of flap reconstruction is discussed, with particular emphasis on the current
      state of nonmicrosurgical perforator based flaps. METHODS: A literature search
      was conducted to study the evolution of flap physiology and reconstruction. Using
      this database, the authors describe the evolution of pedicled perforator flap
      reconstruction. Various examples of perforator-based flaps are discussed in this
      article. RESULTS: The literature review identified examples of scenarios where
      pedicled perforator flaps from various regions of the body are viable options.
      Several clinical cases are presented with respect to each region. CONCLUSION:
      Pedicled perforator flaps are a new concept in nonmicrosurgical perforator flap
      reconstruction.

PMID- 20048614
TI  - Reconstruction of major traumatic segmental bone defects of the tibia with
      vascularized bone transfers.
AB  - BACKGROUND: Segmental bone defects of the tibia after high-energy trauma are limb
      threatening conditions. Multiple treatment options have been proposed, including
      nonvascularized bone grafts, vascularized bone transfers, and callus distraction.
      A series of 41 patients with major segmental defects of the tibia treated with
      vascularized bone reconstruction is presented. METHODS: Forty-one acute or
      nonacute segmental bone defects of the tibia, 4 cm or more in length, were
      included in the series. In acute defects (nine cases), a single-stage or two
      stage reconstruction with vascularized bone transfer was performed. In nonacute
      segmental infected bone defects (32 cases), single-stage reconstruction with
      vascularized bone transfer (seven cases) or two-stage reconstruction with
      vascularized bone transfer (25 cases) was performed. Reconstruction was performed
      with fibular flaps in 38 cases (36 contralateral free and two ipsilateral
      pedicled flaps) and iliac flaps in three cases. Bone fixation was performed with
      screws and external fixation, with early conversion to locking plate internal
      fixation. RESULTS: Two fibular flaps needed urgent revision for venous
      congestion. One fibular flap was lost. Infection after vascularized bone transfer
      occurred in two delayed reconstructions. Bone healing occurred in all cases.
      Stress fractures occurred in three fibular flaps. Time to bone union was 5 to 9
      months, and time to full weight bearing was 9 to 14 months. CONCLUSIONS: The use
      of vascularized bone transfer in the treatment of major segmental tibial defects
      was successful in the present series. The management of bone fixation and
      infection in these cases is discussed.

PMID- 20048615
TI  - Axillary nerve reconstruction in 176 posttraumatic plexopathy patients.
AB  - BACKGROUND: In posttraumatic brachial plexus palsy, shoulder stabilization is of
      utmost importance before reanimation of the distal upper extremity. The aim of
      this study was to present the authors' experience with axillary nerve
      reconstruction in 148 patients with posttraumatic plexopathy. Functional outcomes
      were assessed and correlated with the following factors: severity score,
      denervation time, and donor nerve used. METHODS: The medical records of 176
      patients who underwent axillary nerve reconstruction performed by a single
      surgeon between 1978 and 2006 were reviewed. The results were analyzed in 148
      patients who had adequate follow-up (>24 months). Nerve reconstruction was
      performed using 94 intraplexus donor nerves and 55 extraplexus donor nerves;
      axillary-to-axillary repair was performed in 13 patients, and 15 patients had
      microneurolysis. One hundred forty patients had interposition nerve grafts. A
      total of 135 patients had concomitant neurotization of the suprascapular nerve.
      RESULTS: Results were good or excellent in 45.95 percent of patients. The
      intraplexus donors yielded significantly better shoulder function than the
      extraplexus donors. The length of the nerve graft had a direct influence on
      deltoid recovery. Patients with a severity score higher than 10 attained
      significantly better results than patients with multiple root avulsions. Surgery
      earlier than 4 months yielded significantly better functional outcomes than
      delayed operation of more than 8 months. CONCLUSIONS: Early primary axillary
      nerve reconstruction offers rewarding glenohumeral joint stability and an
      acceptable range of shoulder function. Concomitant neurotization of the
      suprascapular nerve yielded improved outcomes in shoulder abduction and external
      rotation.

PMID- 20048616
TI  - The diminishing presence of plastic surgeons in hand surgery: a critical
      analysis.
AB  - BACKGROUND: A growing trend of diminished presence of plastic surgery within the
      field of hand surgery has been observed in the membership of the American Society
      for Surgery of the Hand, applications for Certificate of Added Qualifications in
      Surgery of the Hand, and applications for hand surgery fellowships. METHODS: The
      American Society for Surgery of the Hand resident education subcommittee has
      investigated this trend, collecting data from the Association of American Medical
      Colleges, the American Board of Orthopaedic Surgery, the American Board of
      Plastic Surgery, the National Residency Matching Program, the Accreditation
      Council for Graduate Medical Education, the American Society for Surgery of the
      Hand, the American Association of Hand Surgery, and the Certificate of Added
      Qualifications in Surgery of the Hand and from an online survey of plastic
      surgery-trained hand surgeons in the United States. RESULTS: These data indicate
      that the subspecialty of hand surgery enjoys growing popularity with increasing
      fellowship applicants annually; uses an effective, fair, and multidisciplinary
      match; and demonstrates continued and healthy growth in its premier academic
      society. Despite these positive indicators, the percentage of new plastic surgery
      diplomates obtaining Certificate of Added Qualifications in Surgery of the Hand
      has decreased from 10 percent (20 applicants per year) to 4 percent (8 applicants
      per year), the percentage of examinees for the Certificate of Added
      Qualifications in Surgery of the Hand originating from plastic surgery training
      backgrounds has decreased from 30 percent to 15 percent, the percentage of the
      overall body of actively practicing plastic surgeons in the United States that
      hold Certificate of Added Qualifications in Surgery of the Hand qualifications is
      steadily decreasing (now to 10 percent), and the plastic surgery membership in
      the American Society for Surgery of the Hand is demonstrating negligible growth
      despite the overall expansion of the American Society for Surgery of the Hand.
      CONCLUSIONS: This report serves as a detailed and systematic account of these
      findings, a balanced interpretation, and a proposal of specific potential
      solutions. These include recommendations for changes in the structure and content
      of plastic surgery training programs and the National Residency Matching Program
      hand surgery fellowship designations.

PMID- 20048617
TI  - Discussion. The diminishing presence of plastic surgeons in hand surgery: a
      critical analysis.

PMID- 20048618
TI  - Resection of amblyogenic periocular hemangiomas: indications and outcomes.
AB  - BACKGROUND: Periocular hemangiomas can induce irreversible amblyopia by multiple
      mechanisms: visual deprivation, refractive error (astigmatism and/or
      anisometropia), or strabismus. There is a subset of complicated periocular
      hemangiomas most effectively managed by resection. METHODS: The authors reviewed
      all patients from 1999 to 2008 with a periocular hemangioma that was either
      completely resected or debulked; whenever necessary, the levator apparatus was
      reinserted. Infants were included in the study if they had complete preoperative
      and postoperative ophthalmic assessments and there was more than a 6-month follow
      up interval. RESULTS: Thirty-three children were treated with a mean operative
      age of 6.2 months and a mean follow-up interval of 48.2 months. The majority of
      hemangiomas were well-localized and caused corneal deformation with astigmatism
      or blepharoptosis. Intralesional or oral corticosteroid administration was
      attempted in almost one-half of patients. Postoperatively, the degree of
      astigmatism was statistically improved: from 3.0 diopters to 1.11 diopters (p <
      0.001). When resection was performed in infants younger than 3 months (19
      patients), astigmatism was less severe preoperatively and the correction was
      slightly greater postoperatively (from 2.76 diopters to 0.80 diopters). Resection
      performed after 3 months (14 patients) of age also resulted in improvement of
      astigmatism (from 3.39 diopters to 1.38 diopters). Reinsertion of the levator
      expansion was required in 34 percent of patients. CONCLUSIONS: The authors
      advocate early resection of a well-localized periocular hemangioma to prevent
      potentially irreversible amblyopia caused by either corneal deformation or
      blepharoptosis. The longer a complicated periocular hemangioma is observed, the
      greater the astigmatism and the less amenable it will be to correction following
      tumor removal.

PMID- 20048619
TI  - Tensor veli palatini preservation, transection, and transection with tensor
      tenopexy during cleft palate repair and its effects on eustachian tube function.
AB  - BACKGROUND: During cleft palate repair, levator sling palatoplasty with tensor
      veli palatini tendon transection significantly improves speech results. However,
      the procedure may pose a risk to eustachian tube function. This study assesses
      the impact of three types of palatoplasty techniques on eustachian tube function:
      no tensor transection, tensor transection alone, and a new addition to the
      palatoplasty technique, tensor tenopexy. METHODS: A retrospective review was
      conducted of all patients undergoing cleft palate repair at two institutions
      between 1997 and 2001. Three cleft palate repair groups were studied: no tensor
      transection (n = 64), tensor transection alone (n = 31), and tensor tenopexy (n =
      52). The percentages of patients requiring myringotomy tubes at each year of age
      were compared among the three groups. RESULTS: By 7 years of age, there was a
      significantly decreased need for myringotomy tubes in patients who underwent no
      tensor transection compared with patients who underwent tensor transection alone
      (38 percent versus 61 percent, respectively; p = 0.05), as well as for patients
      who underwent tensor tenopexy compared with patients who underwent tensor veli
      palatini tendon transection (23 percent versus 61 percent, respectively; p <
      0.001). Also, by the age of 7, there was a trend toward a decreased need for
      myringotomy tubes in patients who underwent tensor tenopexy compared with
      patients who underwent no tensor transection (23 percent versus 38 percent,
      respectively; p = 0.11). CONCLUSIONS: No tensor transection and tensor tenopexy
      significantly decrease the need for myringotomy tubes compared with tensor
      transection alone. There is a small decrease in the need for myringotomy tubes
      when comparing tensor tenopexy with no tensor transection.

PMID- 20048620
TI  - Pharyngeal flap outcomes in nonsyndromic children with repaired cleft palate and
      velopharyngeal insufficiency.
AB  - BACKGROUND: Velopharyngeal insufficiency occurs in 5 to 20 percent of children
      following repair of a cleft palate. The pharyngeal flap is the traditional
      secondary procedure for correcting velopharyngeal insufficiency; however, because
      of perceived complications, alternative techniques have become popular. The
      authors' purpose was to assess a single surgeon's long-term experience with a
      tailored superiorly based pharyngeal flap to correct velopharyngeal insufficiency
      in nonsyndromic patients with a repaired cleft palate. METHODS: The authors
      reviewed the records of all children who underwent a pharyngeal flap performed by
      the senior author (J.B.M.) between 1981 and 2008. The authors evaluated age of
      repair, perceptual speech outcome, need for a secondary operation, and
      complications. Success was defined as normal or borderline sufficient
      velopharyngeal function. Failure was defined as borderline insufficiency or
      severe velopharyngeal insufficiency with recommendation for another procedure.
      RESULTS: The authors identified 104 nonsyndromic patients who required a
      pharyngeal flap following cleft palate repair. The mean age at pharyngeal flap
      surgery was 8.6 +/- 4.9 years. Postoperative speech results were available for 79
      patients. Operative success with normal or borderline sufficient velopharyngeal
      function was achieved in 77 patients (97 percent). Obstructive sleep apnea was
      documented in two patients. CONCLUSION: The tailored superiorly based pharyngeal
      flap is highly successful in correcting velopharyngeal insufficiency, with a low
      risk of complication, in nonsyndromic patients with repaired cleft palate.

PMID- 20048621
TI  - Mercedes Benz pattern craniosynostosis.
AB  - BACKGROUND: The complex craniosynostoses, which include all nonsyndromic multiple
      sutural fusions, represent a small fraction of patients presenting with
      craniosynostosis. Among these are a trisutural fusion, dubbed the "Mercedes Benz
      pattern," involving the sagittal and both lambdoid sutures. The purpose of this
      report is to review the authors' series of this unusual form of craniosynostosis,
      to identify associated anomalies, and to assess treatment outcomes. METHODS: The
      authors conducted a retrospective clinical outcome assessment of all patients
      presenting with Mercedes Benz pattern craniosynostosis. Growth was assessed by
      direct anthropologic measurements, and significance was assessed by the t test.
      RESULTS: Over a 17-year period, 11 of 802 patients presenting with
      craniosynostosis were identified with Mercedes Benz pattern synostosis (1.4
      percent). Three patients had additional sutural involvement and two had
      identifiable genetic syndromes. Seven of 11 (64 percent) had cerebellar tonsillar
      herniation on preoperative imaging, and four symptomatic patients (36 percent)
      have required Chiari decompressions. Three patients have required more than one
      remodeling procedure. Serial postoperative anthropologic measurements identified
      progressive brachycephaly, with diminished growth in both head circumference and
      skull length (mean follow-up, 3.75 years). Cognitive function was grossly normal,
      except for one syndromic patient. CONCLUSIONS: Despite fusion of the sagittal
      suture, the surgical treatment for Mercedes Benz pattern craniosynostosis should
      include skull lengthening, not reduction. The authors' findings for diminished
      postoperative growth suggest that an overcorrection be considered. Fourth or
      fifth sutural involvement correlated with additional corrections. Given the
      observed high incidence for symptomatic cerebellar tonsillar herniation, routine
      magnetic resonance evaluations are recommended for affected individuals.

PMID- 20048622
TI  - Harnessing the potential of the free fibula osteoseptocutaneous flap in mandible
      reconstruction.
AB  - BACKGROUND: The free fibula osteoseptocutaneous flap remains the first choice for
      segmental mandible and contiguous soft-tissue defect reconstructions in most
      situations. METHODS: Several important principles are described that should be
      respected during skin paddle design: fibula contouring, insetting, and fixation,
      and dental implant osseointegration. Recent advancements that address
      difficulties in height contouring, particularly at the anterior segment, are
      highlighted. RESULTS: The presented methods can help provide an optimal
      mandibular reconstruction that restores mechanical functions, facial aesthetics,
      and complete dental competence. CONCLUSION: Efficient interdisciplinary
      communication and teamwork are necessary throughout the longitudinal care of the
      patient if optimal results are to be achieved.

PMID- 20048623
TI  - New technique combined with suture and incision method for creating a more
      physiologically natural double-eyelid.
AB  - BACKGROUND: A combination of incision and nonincision surgical approaches is
      necessary to create a more physiologically natural double-eyelid. METHODS: The
      location of the partial incision and the burying location are determined. Through
      a partial incision, the levator aponeurosis is isolated and fixed to the tarsal
      plate. A single-knot continuous suture is performed. The location of the
      continuous suture passing through the tarsal plate is at a level that is slightly
      lower than that at which the levator aponeurosis is fixed to the tarsal plate.
      RESULTS: A total of 562 patients were operated on from November of 2006 through
      October of 2008. The double-eyelid operation was performed on 386 patients, the
      upper blepharoplasty with skin excision was performed in 91 patients, and a
      secondary operation was performed in 85 patients. Combined mild to moderate
      blepharoptosis was corrected simultaneously in all cases. The follow-up period
      ranged from 6 months to 2 years. Individual patient recovery time varied from 2
      weeks to 2 months. CONCLUSIONS: The advantages of the authors' technique are as
      follows: (1) the process of forming a double-eyelid is natural; (2) the power of
      the levator palpebrae muscle regarding the eye-opening process is transmitted to
      pull up the entire lid margin, allowing the eyes to be easily opened with minimal
      effort; and (3) there is minimal surgical scarring when the eyes are closed.

PMID- 20048624
TI  - Aging of the mandible and its aesthetic implications.
AB  - BACKGROUND: Facial aging is a dynamic process involving the aging of soft-tissue
      and bony structures. In this study, the authors demonstrate how specific bony
      aspects of the mandible change with age in both genders and what impact these
      structural changes may have on overall facial aesthetics. METHODS: Facial bone
      three-dimensional computed tomographic scans were obtained from 120 Caucasian
      subjects (60 women and 60 men). Our study population consisted of 20 male and 20
      female subjects in each of three age categories (20 to 40, 41 to 64, and > or =
      65 years). Edentulous patients were excluded. The following measurements were
      obtained: bigonial width, ramus breadth, ramus height, mandibular body height,
      mandibular body length, and mandibular angle. The data were analyzed with one-way
      analysis of variance and two-tailed t tests, with results considered significant
      at a value of p < 0.05. RESULTS: There was no significant change with regard to
      bigonial width or ramus breadth across age groups for either gender. Ramus
      height, mandibular body height, and mandibular body length decreased
      significantly with age for both genders, whereas the mandibular angle increased
      significantly for both genders with increasing age. CONCLUSIONS: These results
      suggest that the bony elements of the mandible change significantly with age for
      both genders and that these changes, coupled with soft-tissue changes, lead to
      the appearance of the aged lower third of the face.

PMID- 20048625
TI  - Effect of weight loss after bariatric surgery on skin and the extracellular
      matrix.
AB  - BACKGROUND: Obese patients experience dramatic physical and metabolic changes in
      the skin and its collagen. Bariatric surgery is known to result in significant
      improvement in obesity-associated comorbid conditions and metabolic disturbances.
      The aim of this study was to evaluate skin quality following weight loss surgery
      and its suitability to produce an extracellular matrix for use in reconstructive
      procedures. METHODS: During circumferential lipectomy, skin tissue was obtained
      from 10 patients following bariatric surgery. The samples were subjected to
      histologic examination and to study by differential scanning calorimetry. A
      retrospective review of patient records was used to determine time between
      bariatric and body lift procedures and to identify subject demographic and
      clinical data, including body mass index, excess weight loss, and comorbid
      conditions. RESULTS: Plastic surgery followed bariatric surgery by 20.5 +/- 11
      months, and patients experienced an average weight loss of 132.1 +/- 61.0 lb.
      Histologic evaluation of post-bariatric surgery skin samples showed a poorly
      organized collagen structure, elastin degradation, and regions of scar formation
      within macroscopically normal areas. Differential scanning calorimetry showed
      increased enthalpy of phase transition and decreased onset temperature for
      collagen denaturation in striae distensae samples compared with bulk bariatric
      skin samples, consistent with tissue matrix degradation in striae. CONCLUSION:
      Skin tissue in this patient population exhibited significant signs of damage to
      extracellular matrix components despite the duration of time since the bariatric
      procedure.

PMID- 20048626
TI  - Procedural risk for venous thromboembolism in abdominal contouring surgery: a
      systematic review of the literature.
AB  - BACKGROUND: To ensure that patients receive appropriate thromboembolic
      prophylaxis, other specialties have begun using risk stratification models.
      Because these models do not include plastic surgery patients, research must be
      directed toward exploring the risk associated with these operations. A systematic
      review of the literature was performed to address these issues. METHODS: A
      thorough search for all articles discussing abdominal contouring surgery was
      conducted. Data were collected from this institution through a retrospective
      chart review and included in the analysis. Procedures were divided into four
      groups, dependent on what was reported, as follows: abdominoplasty alone,
      abdominoplasty with an intraabdominal procedure, abdominoplasty with another
      plastic surgical procedure, and circumferential abdominoplasty. Frequencies of
      venous thromboembolism were recorded. Chi-square analysis was performed to
      examine for statistical differences. RESULTS: One hundred fourteen articles were
      reviewed; 30 articles were included in the analysis. Circumferential
      abdominoplasty was associated with the highest venous thromboembolism rate (3.40
      percent). This was statistically higher than the thromboembolic rate of
      abdominoplasty (0.35 percent) (p < 0.0001) and abdominoplasty with concomitant
      plastic surgery (0.79 percent) (p < 0.0001). Abdominoplasty combined with an
      intraabdominal procedure was associated with the second highest rate of
      thromboembolism (2.17 percent). This rate was higher than abdominoplasty alone (p
      < 0.001) and abdominoplasty with concomitant plastic surgery (p = 0.02).
      CONCLUSIONS: Circumferential abdominoplasty and abdominoplasty performed in
      combination with an intraabdominal procedure were demonstrated to have
      significantly increased risk for venous thromboembolism. Patients undergoing
      these procedures should be risk stratified and have perioperative prophylaxis
      managed accordingly. It is suggested that both of these operations be placed into
      a higher exposing risk category within the modified Davison-Caprini risk
      assessment model.

PMID- 20048627
TI  - Difficulties with subpectoral augmentation mammaplasty and its correction: the
      role of subglandular site change in revision aesthetic breast surgery.
AB  - BACKGROUND: Difficulties that arise with subpectoral breast implant placement
      include the following: malpositioning of the implant; improper superior
      contouring; and unnatural movement with chest muscle contraction. Correction of
      these deformities is easily achieved by removal of the subpectoral implant,
      resuspension of the pectoralis major muscle to the chest wall, and reaugmentation
      with a new implant in the subglandular plane. This study defines a correction
      modality for the adverse results of subpectoral implant placement in augmentation
      mammaplasty. METHODS: Pectoralis major resuspension was performed in 36 patients
      undergoing revision aesthetic breast surgery from 1995 to 2006. All patients had
      previously placed subpectoral breast implants performed elsewhere with unwanted
      movement, malposition, and/or capsular contracture. All patients underwent
      explantation of the breast implant, modified capsulectomy, pectoralis major
      resuspension, and reaugmentation of the breast in the subglandular position. In
      cases of symmastia, medial capsulodesis and sternal bolster sutures were used.
      Patients were evaluated for resolution of symptoms, satisfaction, and
      complications. RESULTS: Malposition (62 percent), capsular contracture (53
      percent), and symmastia (10 percent) were the most common indications for
      revision, but 100 percent of patients were dissatisfied with abnormal breast
      movement. The average follow-up time was 20 months. The silicone implants were
      commonly used, with an average volume change decrease of 27 cc. Unwanted implant
      movement was eliminated completely (100 percent), symmastia was corrected (100
      percent), and capsular contraction was significantly decreased in each respective
      group. Patient satisfaction with this procedure was high, with a low complication
      rate. CONCLUSIONS: Pectoralis major resuspension can be performed successfully in
      aesthetic breast surgery. It can be applied safely to correct problems of
      unwanted implant movement, symmastia implant malposition, and capsular
      contraction. The use of silicone gel implants in a novel tissue plane may be
      beneficial in this diverse, reoperative patient population.

PMID- 20048628
TI  - Microdermabrasion: an evidence-based review.
AB  - Microdermabrasion is a popular technique used in the treatment of several skin
      problems, including acne, acne scarring, striae distensae, and photoaging. This
      article will review the relevant literature and use an evidence-based approach to
      evaluate the clinical efficacy of microdermabrasion in skin care. In summary,
      microdermabrasion appears to be a procedure that can produce changes in dermal
      matrix constituents and result in improvement in skin contour irregularities. It
      may also be beneficial in improving transepidermal delivery of certain
      medications. Its role in the treatment of dyschromias and acne vulgaris is
      limited.

PMID- 20048629
TI  - Antioxidants and skin care: the essentials.

PMID- 20048630
TI  - Transconjunctival blepharoplasty for upper and lower eyelids.
AB  - BACKGROUND: Transconjunctival blepharoplasty remains a popular and safe technique
      to treat periorbital aging. In the lower lid, it can be used successfully for
      orbital fat excision, redistribution, or septal tightening. In the upper lid,
      transconjunctival blepharoplasty has a role in removal of the nasal fat pad via
      an isolated, direct approach. METHODS: The authors review anatomy, indications,
      and surgical approaches for upper and lower lid transconjunctival blepharoplasty.
      RESULTS: Potential complications, patient results, and the senior author's
      personal series are discussed. CONCLUSIONS: In the lower lid, this technique can
      be advocated in an effort to avoid lower lid complications such as sclera show or
      lid malposition. In the upper lid, it can be effective in treating isolated fat
      pads with minimal skin excess.

PMID- 20048631
TI  - Mammometrics: the standardization of aesthetic and reconstructive breast surgery.

PMID- 20048632
TI  - Mirror, mirror on the wall: the interface between illusion and reality in
      aesthetic surgery.

PMID- 20048636
TI  - Demineralized bone matrix and resorbable mesh bilaminate cranioplasty.

PMID- 20048637
TI  - Allograft maxillary composite face transplantation.

PMID- 20048639
TI  - Facial paralysis measurement with a handheld ruler.

PMID- 20048640
TI  - Propranolol as first-line treatment for infantile hemangiomas.

PMID- 20048642
TI  - Anatomical basis for the keystone island flap in the upper thigh.

PMID- 20048643
TI  - Calf augmentation with autologous tissue injection.

PMID- 20048646
TI  - Evidence-based medicine?

PMID- 20048650
TI  - Safety during regional anesthesia: what do we know and how can we improve our
      practice?

PMID- 20048651
TI  - Practice guidelines often fail to keep pace with the rapid evolution of medicine:
      a call for clinicians to remain vigilant and revisit their own practice patterns.

PMID- 20048652
TI  - Pulsed radiofrequency: rebel without cause.

PMID- 20048653
TI  - The efficiency of pulsed radiofrequency application on L5 and l6 dorsal roots in
      rabbits developing neuropathic pain.
AB  - BACKGROUND: Injury of a peripheral nerve may lead to neuropathic pain, a form of
      chronic pain that does not respond to traditional pain therapies. The aim of this
      study was to investigate the effect of pulsed radiofrequency (PRF) applied to the
      L5 and L6 dorsal roots on the neuropathic pain that develops after sciatic nerve
      injury in rabbits. METHODS: In this study, 18 New Zealand rabbits were used.
      These were divided into 3 groups. In groups 1 and 2, the left sciatic nerve was
      tightly ligated as a partial ligation model with 4-0 silk sutures. Group 3 was a
      sham group. Pulsed radiofrequency was applied to group 1 rabbits on both dorsal
      roots at 42 degrees C for 8 mins. The responses of all the groups to thermal and
      mechanical stimuli were measured for a period of 4 weeks after this process.
      RESULTS: Ten days after ligation of the left sciatic nerve and before PRF
      application, neuropathic pain occurred; the responses of groups 1 and 2 to the
      hot plate test and to the mechanical stimulus were lower (P < 0.005) when
      compared with the baseline values. There were no statistically significant
      differences between baseline values and group 1 rabbits' responses to the hot
      plate test 2 weeks after the application of PRF or to the mechanical stimulus 3
      weeks after RF application. The decrease seen in group 2 persisted after 4 weeks
      (P < 0.001). CONCLUSIONS: The hyperalgesia that develops as a result of
      neuropathic pain in rabbits was observed to be reduced by PRF application.

PMID- 20048654
TI  - A prospective, randomized comparison between single- and double-injection
      ultrasound-guided infraclavicular brachial plexus block.
AB  - BACKGROUND: This prospective, randomized, observer-blinded study compared single-
      and double-injection ultrasound-guided infraclavicular brachial plexus block for
      upper extremity surgery. METHODS: Eighty-eight patients were randomly allocated
      to receive a single-injection (n = 44) or double-injection (n = 44) ultrasound
      guided infraclavicular block. The main outcome variable was the onset time. A
      blinded observer recorded the onset time, block-related pain scores, success rate
      (surgical anesthesia), and the incidence of complications. Performance time
      (defined as the sum of imaging and needling times) and the number of needle
      passes were also recorded during the performance of the block. The total
      anesthesia-related time was defined as the sum of the performance and onset
      times. RESULTS: No differences in imaging, needling, performance, and onset and
      total anesthesia-related times were found between the 2 groups. There were no
      differences in the rate of surgical anesthesia (93.1%-97.7%). The number of
      needle passes was also similar; however, the double-injection technique resulted
      in slightly less procedural discomfort (1.1 [SD, 1.6] vs 2.1 [SD, 2.1]; P =
      0.021). There were no differences in the incidence of adverse events. CONCLUSION:
      The double-injection ultrasound-guided infraclavicular block provides no
      significant advantages compared with its single-injection counterpart.

PMID- 20048655
TI  - Analgesic effectiveness of a continuous versus single-injection interscalene
      block for minor arthroscopic shoulder surgery.
AB  - BACKGROUND AND OBJECTIVES: The utility of continuous perineural infusions for
      lesser painful shoulder procedures is not well established. We hypothesized that
      the addition of a continuous interscalene ropivacaine infusion to a single
      injection interscalene block would improve analgesia after minor arthroscopic
      shoulder surgery. METHODS: An ultrasound-guided interscalene catheter targeting
      the C5-C6 roots/superior trunk was placed preoperatively in patients undergoing
      arthroscopic subacromial decompression, excision lateral clavicle, or
      stabilization. Ropivacaine 0.5% 30 mL was administered via this catheter before
      surgery was conducted under general anesthesia. All patients received
      dexamethasone and ondansetron antiemetic prophylaxis. At surgery conclusion,
      patients were randomly assigned to catheter removal in the postanesthesia care
      unit ("SS," n = 30) or to an elastomeric infusion of ropivacaine 0.2% 2 mL/hr
      with patient-controlled 5-mL boluses every hour ("Continuous," n = 31).
      Multimodal analgesia (acetaminophen, diclofenac, and rescue tramadol) was
      administered in both groups. Patients were questioned on postoperative days 1 and
      2 for numerical rating pain score (0-10), supplemental tramadol consumption, and
      adverse effects of treatment. RESULTS: Median (quartiles) worst numerical rating
      pain score was lower in the Continuous group on day 1 on movement (SS = 4 [3-6],
      Continuous = 2 [0-4], P = 0.008) and at rest (SS = 2 [2-5], Continuous = 1 [0-3],
      P = 0.007) but was similar between groups on day 2. Median (quartiles) tramadol
      tablet consumption was lower in the Continuous group on both day 1 (SS = 1 [0-2],
      Continuous = 0 [0-0], P < 0.001) and day 2 (SS = 1 [0-2], Continuous = 0 [0-1], P
      = 0.017). Adverse effects of treatment were similar between groups except for
      numerically rated arm numbness, which was higher for the Continuous group. One
      patient in the SS group required 2 nights of hospitalization for intravenous
      opioid. CONCLUSIONS: After minor arthroscopic shoulder surgery, the addition of a
      continuous interscalene ropivacaine infusion to a single-shot interscalene block
      reduces pain, especially with movement, during the first 24 hrs.

PMID- 20048656
TI  - Needle-induced paresthesiae during single-shot spinal anesthesia: a comparison of
      sitting versus lateral decubitus position.
AB  - BACKGROUND AND OBJECTIVES: Paresthesiae occasionally occur during spinal puncture
      or injection of local anesthetic for spinal anesthesia. No information is
      currently available regarding the effects of the patient's position on the
      incidence of needle-induced paresthesiae. The purpose of this prospective,
      observational study was to compare the occurrence of needle-induced paresthesiae
      in patients who received single-shot spinal anesthesia in the sitting position or
      in the lateral decubitus position. METHODS: A total of 620 patients operated on
      under spinal anesthesia were included. Spinal anesthesia was performed in the
      sitting position in 142 patients and in the lateral decubitus position in 478
      patients. All blocks were performed with a 25-gauge, 90-mm, Sprotte needle, at
      the L3-L4 or L4-L5 level. Patients' demographics, patients' position (lateral
      decubitus or sitting), number of skin punctures, incidence of paresthesiae, and
      success of the anesthesia were recorded. RESULTS: The overall incidence of
      paresthesiae was higher in the lateral decubitus position (16.95%) compared with
      the sitting position (9.15%) (P = 0.0230). The number of punctures and the
      success rate were similar in both positions. Studying the incidence of
      paresthesiae for each position, when performing 1 or more punctures, there was no
      position-related difference noted if a single-needle puncture was sufficient to
      perform the block (8.0% in the lateral decubitus group versus 5.1% in the sitting
      group) (P = 0.3305). This difference between positions was significant when more
      than a single-needle puncture was required (34.1% in the lateral decubitus group
      versus 18.6% in the sitting group) (P = 0.0497). CONCLUSIONS: Patient's position
      may influence the occurrence of needle-induced paresthesiae during spinal
      anesthesia. Lateral decubitus position resulted in a higher incidence of
      paresthesiae than the sitting position. However, there is no position-related
      difference noted if a single-needle puncture is sufficient to perform the block.

PMID- 20048657
TI  - Local anesthetic effects on human neutrophil priming and activation.
AB  - BACKGROUND: The anti-inflammatory effects of local anesthetics (LAs) are well
      documented. Local anesthetics in micromolar concentrations inhibit extracellular
      oxygen release in isolated neutrophils; the underlying mechanism seems to be an
      inhibition of leukocyte priming. It remains unclear, however, if first, these
      effects also can be observed in whole blood, and second, if the priming of other
      neutrophil functions is similarly attenuated by LAs. Furthermore, the effects of
      LAs on intracellular generation of oxidative species remain to be investigated.
      METHODS: Whole-blood samples from healthy volunteers were incubated for 0, 1, or
      3 hrs with different concentrations (10 to 10 M) of either lidocaine,
      ropivacaine, QX314, or NaCl 0.9% as control. Dihydroethidium was added to
      quantify oxidative burst. Samples were primed with platelet-activating factor
      (PAF, 10 M) and/or activated with formyl-methyl-leucyl-phenylalanine (10 M) for
      15 mins each. After staining for CD11b and lysis of erythrocytes, samples were
      analyzed by flow cytometry. RESULTS: Priming of leukocytes is a relevant
      mechanism in whole blood. Platelet-activating factor stimulates the priming of
      oxidative burst and CD11b expression. Lidocaine up to millimolar concentrations
      did not affect the PAF priming and formyl-methyl-leucyl-phenylalanine activation
      of oxidative burst. The priming of CD11b expression and the priming and
      activation of changes in cell morphology were significantly attenuated by
      lidocaine. CONCLUSIONS: The intracellular generation of reactive oxygen species
      remains largely unaffected by LAs in clinical concentrations. This suggests that
      the anti-inflammatory effects of LAs do not interfere with the host defense.

PMID- 20048658
TI  - Long-lasting analgesic effects of intraoperative thoracic epidural with
      bupivacaine for liver resection.
AB  - OBJECTIVES: Continuous epidural analgesia may be considered in liver resection
      but is often avoided because of possible coagulopathies and the risk of epidural
      hematoma in the postoperative period. On the other hand, there is no coagulation
      defect during the surgery. Effective prevention of postoperative pain may require
      continuous sensory ablation throughout the surgery event. METHODS: A prospective,
      randomized, double-blind study was conducted to evaluate the efficacy of
      intraoperative epidural anesthesia on postoperative morphine consumption via
      patient-controlled analgesia after liver surgery in 2 groups of patients. One
      group (epidural) received, intraoperatively, thoracic epidural bupivacaine
      perfusion (0.5% at 3 mL/hr) added to preoperative intrathecal morphine (0.5 mg)
      and fentanyl (15 microg). The other group (placebo) was administered the same
      intrathecal narcotics but with a sham epidural. Forty-four patients scheduled for
      major liver resection (> or =2 segments) were recruited. Patient-controlled
      analgesia morphine consumption, pain at rest and with movement, sedation, nausea,
      pruritus, and respiratory frequency were evaluated at 6, 9, 12, 18, 24, 36, and
      48 hrs after intrathecal morphine injection. RESULTS: Patients in the placebo
      group consumed twice as much morphine during each time interval than patients in
      the epidural group (at 48 hrs: 123 [SD, 46] vs 59 [SD, 25] mg; P < 0.0001). Pain
      evaluation on visual analog scale at rest and on movement was lower in the
      epidural group (P = 0.017 and P = 0.037). CONCLUSION: Intraoperative thoracic
      epidural infusion of bupivacaine, added to intrathecal morphine, decreased
      postoperative morphine consumption with better pain relief compared with the
      placebo.

PMID- 20048659
TI  - Executive summary: regional anesthesia in the patient receiving antithrombotic or
      thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine
      Evidence-Based Guidelines (Third Edition).

PMID- 20048661
TI  - Regional Anaesthesia adventures: Carl Koller Lecture, ESRA 2008.

PMID- 20048662
TI  - The truth, the whole truth, and nothing but the truth.

PMID- 20048663
TI  - Clopidogrel and neuraxial block: the role of the PFA II and P2Y12 assays.

PMID- 20048665
TI  - Most reported subdural injections are not in the subdural space, they are
      intradural! Reply to dr. Collier.

PMID- 20048666
TI  - Re: Most reported subdural injections are not in the subdural space, they are
      intradural! Reply to dr. Collier.

PMID- 20048667
TI  - An electrocardiograph artifact caused by peripheral nerve stimulation during an
      interscalene brachial plexus nerve block.

PMID- 20048668
TI  - Re: Ultrasound-guided posterior approach for the placement of a continuous
      interscalene catheter. Reply to dr. Narouze.

PMID- 20048669
TI  - Re: Bad needles can't do good blocks. Reply to dr. Forget.

PMID- 20048670
TI  - Re: Effects of local anesthetic concentration and dose on continuous interscalene
      nerve blocks: a dual-center, randomized, observer-masked, controlled study. Reply
      to dr. Borgeat.

PMID- 20048671
TI  - Re: Implications of a permanent cardiac pacemaker in peripheral nerve blockade.
      Reply to dr. Dolan.

PMID- 20048672
TI  - Paraffin tissue microarrays constructed with a cutting board and cutting board
      arrayer.
AB  - Paraffin tissue microarrays (PTMAs) are blocks of paraffin containing up to 1300
      paraffin tissue core biopsies (PTCBs). Normally, these PTCBs are punched from
      routine paraffin tissue blocks, which contain tissues of differing thicknesses.
      Therefore, the PTCBs are of different lengths. In consequence, the sections of
      the deeper portions of the PTMA do not contain all of the desired PTCBs. To
      overcome this drawback, cutting boards were constructed from panels of plastic
      with a thickness of 4 mm. Holes were drilled into the plastic and filled
      completely with at least one PTCB per hole. After being trimmed to a uniform
      length of 4 mm, these PTCBs were pushed from the cutting board into corresponding
      holes in a recipient block by means of a plate with steel pins. Up to 1000
      sections per PTMA were cut without any significant loss of PTCBs, thereby
      increasing the efficacy of the PTMA technique.

PMID- 20048673
TI  - Implementation of a Canadian external quality assurance program for breast cancer
      biomarkers.

PMID- 20048674
TI  - Cell proliferation index determination by immunohistochemical detection of hCDC47
      protein.
AB  - A member of the human minichromosome maintenance complex protein family, hCDC47
      (alias MCM7) has been identified as a component of the regulatory mechanism in
      cell proliferation. The expression of this protein, as determined by
      immunohistochemistry, was investigated to determine its application as a
      proliferation marker. A mouse monoclonal antibody (Clone 47DC141, NeoMarkers,
      Fremont CA) raised against recombinant hCDC47 protein was tested against a wide
      range of tissues. Immunoreaction patterns were determined in normal and
      neoplastic, human tissues, including skin, tonsils and lymph nodes, primary, and
      metastatic brain tumors. The protein was detected in the nuclei of both, normal
      and neoplastic proliferating cells. Similarly, we also examined the distribution
      of hCDC47 in normal rat and mouse tissues, and rodent and human tumors grown in
      nude mice.The pattern of immunolocalization was identical to that seen in human
      tissue, with positive nuclear immunoreaction readily identified in proliferating
      cells. Western immunoblot was carried out on extracts from PANC cells (human
      pancreatic adenocarcinoma cell line) to confirm the specificity of the protein.
      To correlate Ki67 protein immunoexpression with hCDC47 antibody reactivity,
      semiquantitative comparisons were carried out on parallel tissue sections. There
      was excellent correlation in the distribution pattern of the 2 markers, although
      hCDC47 was more sensitive.Thus this marker may have important clinical and
      research applications because of its activity in formalin-fixed, paraffin
      embedded, proliferating, normal, and neoplastic tissue. More significantly, its
      application to animal tissue makes it a reliable and easy to use, proliferation
      marker for experimental studies.

PMID- 20048675
TI  - The 1918 influenza pandemic: lessons for 2009 and the future.
AB  - The 1918 to 1919 H1N1 influenza pandemic is among the most deadly events in
      recorded human history, having killed an estimated 50 to 100 million persons.
      Recent H5N1 avian influenza epizootics associated with sporadic human fatalities
      have heightened concern that a new influenza pandemic, one at least as lethal as
      that of 1918, could be developing. In early 2009, a novel pandemic H1N1 influenza
      virus appeared, but it has not exhibited unusually high pathogenicity.
      Nevertheless, because this virus spreads globally, some scientists predict that
      mutations will increase its lethality. Therefore, to accurately predict, plan,
      and respond to current and future influenza pandemics, we must first better
      understand the events and experiences of 1918. Although the entire genome of the
      1918 influenza virus has been sequenced, many questions about the pandemic it
      caused remain unanswered. In this review, we discuss the origin of the 1918
      pandemic influenza virus, the pandemic's unusual epidemiologic features and the
      causes and demographic patterns of fatality, and how this information should
      impact our response to the current 2009 H1N1 pandemic and future pandemics. After
      92 yrs of research, fundamental questions about influenza pandemics remain
      unanswered. Thus, we must remain vigilant and use the knowledge we have gained
      from 1918 and other influenza pandemics to direct targeted research and pandemic
      influenza preparedness planning, emphasizing prevention, containment, and
      treatment.

PMID- 20048676
TI  - Intensive care unit-acquired weakness.
AB  - OBJECTIVE: Severe weakness is being recognized as a complication that impacts
      significantly on the pace and degree of recovery and return to former functional
      status of patients who survive the organ failures that mandate life-support
      therapies such as mechanical ventilation. Despite the apparent importance of this
      problem, much remains to be understood about its incidence, causes, prevention,
      and treatment. DESIGN: Review from literature and an expert round-table. SETTING:
      The Brussels Round Table Conference in 2009 convened more than 20 experts in the
      fields of intensive care, neurology, and muscle physiology to review current
      understandings of intensive care unit-acquired weakness and to improve clinical
      outcome. MAIN RESULTS: Formal electrophysiological evaluation of patients with
      intensive care unit-acquired weakness can identify peripheral neuropathies,
      myopathies, and combinations of these disorders, although the correlation of
      these findings to weakness measurable at the bedside is not always precise. For
      routine clinical purposes, bedside assessment of neuromuscular function can be
      performed but is often confounded by complicating factors such as sedative and
      analgesic administration. Risk factors for development of intensive care unit
      acquired weakness include bed rest itself, sepsis, and corticosteroid exposure. A
      strong association exists between weakness and long-term ventilator dependence;
      weakness is a major determinant of patient outcomes after surviving acute
      respiratory failure and may be present for months, or indefinitely, in the
      convalescence phase of critical illness. CONCLUSION: Although much has been
      learned about the physiology and cell and molecular biology of skeletal and
      diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis,
      the application of these understandings to the bedside requires more study in
      both bench models and patients. Although a trend toward greater immobilization
      and sedation of patients has characterized the past several decades of intensive
      care unit care, recent studies have demonstrated that early physical and
      occupational therapy, including during the period of intubation and ventilator
      support, can be safely performed and will likely improve patient outcomes with
      regard to functional status.

PMID- 20048677
TI  - Impact of time to antibiotics on survival in patients with severe sepsis or
      septic shock in whom early goal-directed therapy was initiated in the emergency
      department.
AB  - OBJECTIVE: To study the association between time to antibiotic administration and
      survival in patients with severe sepsis or septic shock in whom early goal
      directed therapy was initiated in the emergency department. DESIGN: Single-center
      cohort study. SETTING: The emergency department of an academic tertiary care
      center from 2005 through 2006. PATIENTS: Two hundred sixty-one patients
      undergoing early goal-directed therapy. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Effects of different time cutoffs from triage to antibiotic
      administration, qualification for early goal-directed therapy to antibiotic
      administration, triage to appropriate antibiotic administration, and
      qualification for early goal-directed therapy to appropriate antibiotic
      administration on in-hospital mortality were examined. The mean age of the 261
      patients was 59 +/- 16 yrs; 41% were female. In-hospital mortality was 31%.
      Median time from triage to antibiotics was 119 mins (interquartile range, 76-192
      mins) and from qualification to antibiotics was 42 mins (interquartile range, 0
      93 mins). There was no significant association between time from triage or time
      from qualification for early goal-directed therapy to antibiotics and mortality
      when assessed at different hourly cutoffs. When analyzed for time from triage to
      appropriate antibiotics, there was a significant association at the <1 hr
      (mortality 19.5 vs. 33.2%; odds ratio, 0.30 [95% confidence interval, 0.11-0.83];
      p = .02) time cutoff; similarly, for time from qualification for early goal
      directed therapy to appropriate antibiotics, a significant association was seen
      at the < or =1 hr (mortality 25.0 vs. 38.5%; odds ratio, 0.50 [95% confidence
      interval, 0.27-0.92]; p = .03) time cutoff. CONCLUSIONS: Elapsed times from
      triage and qualification for early goal-directed therapy to administration of
      appropriate antimicrobials are primary determinants of mortality in patients with
      severe sepsis and septic shock treated with early goal-directed therapy.

PMID- 20048678
TI  - Surgical "buy-in": the contractual relationship between surgeons and patients
      that influences decisions regarding life-supporting therapy.
AB  - OBJECTIVE: There is a general consensus by intensivists and nonsurgical providers
      that surgeons hesitate to withdraw life-sustaining therapy on their operative
      patients despite a patient's or surrogate's request to do so. The objective of
      this study was to examine the culture and practice of surgeons to assess
      attitudes and concerns regarding advance directives for their patients who have
      high-risk surgical procedures. DESIGN: A qualitative investigation using one-on
      one, in-person interviews with open-ended questions about the use of advance
      directives during perioperative planning. Consensus coding was performed using a
      grounded theory approach. Data accrual continued until theoretical saturation was
      achieved. Modeling identified themes and trends, ensuring maximal fit and
      faithful data representation. SETTING: Surgical practices in Madison and
      Milwaukee, WI. SUBJECTS: Physicians involved in the performance of high-risk
      surgical procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      describe the concept of surgical "buy-in," a complex process by which surgeons
      negotiate with patients a commitment to postoperative care before undertaking
      high-risk surgical procedures. Surgeons describe seeking a commitment from the
      patient to abide by prescribed postoperative care, "This is a package deal, this
      is what this operation entails," or a specific number of postoperative days, "I
      will contract with them and say, 'look, if we are going to do this, I am going to
      need 30 days to get you through this operation.'" "Buy-in" is grounded in a
      surgeon's strong sense of responsibility for surgical outcomes and can lead to
      surgeon unwillingness to operate or surgeon reticence to withdraw life-sustaining
      therapy postoperatively. If negotiations regarding life-sustaining interventions
      result in treatment limitation, a surgeon may shift responsibility for
      unanticipated outcomes to the patient. CONCLUSIONS: A complicated relationship
      exists between the surgeon and patient that begins in the preoperative setting.
      It reflects a bidirectional contract that is assumed by the surgeon with distinct
      implications and consequences for surgeon behavior and patient care.

PMID- 20048679
TI  - T-cell dysfunction in HIV-1-infected patients with impaired recovery of CD4 cells
      despite suppression of viral replication.
AB  - INTRODUCTION: CD4 T-cell recovery is impeded in some HIVinfected patients despite
      successful combination antiretroviral therapy (cART) with suppressed HIV RNA. We
      hypothesized that T-cell dysfunction would be increased in these patients.
      METHODS: In the Danish HIV Cohort Study, we identified HIV-1-infected patients
      initiating cART with a CD4 cell count <100 cells per microliter, followed by HIV
      RNA <50 copies per milliliter for 3 years. Patients with a CD4 count <200 cells
      per microliter after 3 years were identified as cases; 42 patients with a CD4
      count > or = 200 cells per microliter were selected as controls. Six-color flow
      cytometry was performed on whole blood. Cytokine levels in supernatants from
      whole blood stimulations were assessed. RESULTS: The case and control groups
      comprised 18 and 35 patients, respectively. Cases were older than controls
      (median: 54/46 years). The fraction of CD28+ cells was decreased among cases in
      the CD4+ and CD8+ T-cell subsets (P = 0.0014/P = 0.0349) and in the corresponding
      naive subsets (P = 0.0011/P , 0.0001). Cases had higher expression of human
      leukocyte antigen (HLA)-DR on naive CD4 and CD8 T cells (P = 0.0007/P = 0.0028).
      The production of interleukin (IL)-10 and IL-2 to phytohemagglutinin was
      decreased in cases (P < 0.0001/P = 0.019). CONCLUSIONS: Patients with impaired
      CD4 recovery shared a dysregulated T-cell phenotype with low CD28, high HLA-DR
      expression, and low IL-2 and IL-10 production.

PMID- 20048680
TI  - Provider-focused intervention increases adherence-related dialogue but does not
      improve antiretroviral therapy adherence in persons with HIV.
AB  - BACKGROUND: Physicians' limited knowledge of patients' antiretroviral adherence
      may reduce their ability to perform effective adherence counseling. METHODS: We
      conducted a randomized, cross-over study of an intervention to improve
      physicians' knowledge of patients' antiretroviral adherence. The intervention was
      a report given to the physician before a routine office visit that included data
      on Medication Event Monitoring System and self-reported data on antiretroviral
      adherence, patients' beliefs about antiretroviral therapy, reasons for missed
      doses, alcohol and drug use, and depression. We audio recorded 1 intervention and
      1 control visit for each patient to analyze differences in adherence-related
      dialogue. RESULTS: One hundred fifty-six patients were randomized, and 106
      completed all 5 study visits. Paired audio recorded visits were available for 58
      patients. Using a linear regression model that adjusted for site and baseline
      Medication Event Monitoring System adherence, adherence after intervention visits
      did not differ significantly from control visits (2.0% higher, P = 0.31, 95%
      confidence interval: -1.95% to 5.9%). There was a trend toward more total
      adherence-related utterances (median of 76 vs. 49.5, P = 0.07) and a significant
      increase in utterances about the current regimen (median of 51.5 vs. 32.5, P =
      0.0002) in intervention compared with control visits. However, less than 10% of
      adherence-related utterances were classified as "problem solving" in content, and
      one third of physicians' problem-solving utterances were directive in nature.
      CONCLUSIONS: Receipt of a detailed report before clinic visits containing data
      about adherence and other factors did not improve patients' antiretroviral
      adherence. Analyses of patient-provider dialogue suggests that providers who care
      for persons with HIV may benefit from training in adherence counseling
      techniques.

PMID- 20048681
TI  - Changes in the composition of the human fecal microbiome after bacteriotherapy
      for recurrent Clostridium difficile-associated diarrhea.
AB  - Clostridium difficile-associated disease (CDAD) is the major known cause of
      antibiotic-induced diarrhea and colitis, and the disease is thought to result
      from persistent disruption of commensal gut microbiota. Bacteriotherapy by way of
      fecal transplantation can be used to treat recurrent CDAD, which is thought to
      reestablish the normal colonic microflora. However, limitations of conventional
      microbiologic techniques have, until recently, precluded testing of this idea. In
      this study, we used terminal-restriction fragment length polymorphism and 16S
      rRNA gene sequencing approaches to characterize the bacterial composition of the
      colonic microflora in a patient suffering from recurrent CDAD before and after
      treatment by fecal transplantation from a healthy donor. Although the patient's
      residual colonic microbiota, prior to therapy was deficient in members of the
      bacterial divisions-Firmicutes and Bacteriodetes, transplantation had a dramatic
      impact on the composition of the patient's gut microbiota. By 14 days
      posttransplantation, the fecal bacterial composition of the recipient was highly
      similar to that of the donor and was dominated by Bacteroides spp. strains and an
      uncharacterized butyrate producing bacterium. The change in bacterial composition
      was accompanied by resolution of the patient's symptoms. The striking similarity
      of the recipient's and donor's intestinal microbiota following after
      bacteriotherapy suggests that the donor's bacteria quickly occupied their
      requisite niches resulting in restoration of both the structure and function of
      the microbial communities present.

PMID- 20048682
TI  - Independent factors associated with early outcome in Chinese cirrhotic patients
      after cessation of initial esophageal variceal hemorrhage.
AB  - BACKGROUND, PURPOSE, AND METHOD: Cirrhotic patients with acute esophageal
      variceal (EV) hemorrhage are characterized by high mortality. This study was
      conducted to investigate the independent indicators of mortality in Chinese
      cirrhotic patients within 6 weeks after cessation of initial EV bleeding. Ninety
      seven consecutive cirrhotic patients with EV bleeding but without evidence of
      infection who were admitted to our hospital between December 2006 and February
      2009 were retrospectively analyzed. Ten patients who died and 87 patients who
      survived were enrolled in the mortality and survival groups, respectively. The
      characteristics and laboratory data at admission of patients in the 2 groups were
      compared. Time of death in the mortality group, rebleeding and infection in both
      the mortality and survival groups were also evaluated. RESULTS: The incidence of
      mortality after cessation of initial EV bleeding was 10.3% (10/97). Incidences of
      infection and rebleeding were significantly higher in the mortality group than in
      the survival group (60% vs. 21%, 70% vs. 8%). Other parameters such as age, sex,
      etiology of liver cirrhosis, severity of liver disease (ascites, spleen diameter,
      platelet count, hepatocellular carcinoma, portal vein thrombosis), severity of EV
      bleeding (hemoglobin, blood pressure, requirements of blood transfusion), and
      differential vasoactive medications had no significant influence on incidence of
      mortality. All deaths were caused by rebleeding or sepsis, and all rebleeding
      occurred before infection. Most (67%) patients with rebleeding had postbanding
      ulcer bleeding. Generally, mortality, rebleeding, and infection occurred within 2
      weeks after cessation of initial EV bleeding. CONCLUSIONS: This study provides
      evidence that the incidence of early mortality after cessation of initial EV
      bleeding is significantly associated with bacterial infection and rebleeding.
      Rebleeding can increase the possibility of infection. Therefore, prevention of
      infection and rebleeding plays a major role in improving the early outcome in
      Chinese cirrhotic patients with EV bleeding.

PMID- 20048683
TI  - Delayed release phosphatidylcholine in chronic-active ulcerative colitis: a
      randomized, double-blinded, dose finding study.
AB  - BACKGROUND: In 2 preceding studies, delayed release phosphatidylcholine (rPC) was
      found to (a) improve disease activity and (b) withdraw steroids in patients with
      chronic-active ulcerative colitis. GOAL: Objective of the study was to determine
      the most effective rPC dose with least adverse events. STUDY: A randomized, dose
      controlled, double-blinded study. Four groups of 10 patients each with nonsteroid
      treated, chronic-active ulcerative pancolitis with a clinical activity index
      (CAI) and endoscopic activity index (EAI) >or=7. Patients were treated with oral
      rPC at doses of 0.5, 1, 3, and 4 g daily over 12 weeks. RESULTS: The CAI changes
      from baseline to the end of the study were 2.5 (0.5 g), 7.0 (1 g), 5.5 (3 g), and
      6.0 (4 g dose arm). Significant improvement of the CAI was registered between the
      lowest rPC dose of 0.5 g (control group) and all higher doses of 1.0, 3.0, and
      4.0-g rPC (P<or=0.05). Remission (CAI <or=3) was reached in 5/10 and 6/10
      patients in the 3 and 4-g dose groups compared with no patients in the 0.5-g arm
      (P=0.033). In the 1-g dose group only 3/10 patients reached remission (P=0.21).
      The rates of clinical response (>or=50% CAI improvement) were 70% in all of the
      effective dose groups (1 to 4 g, P=0.003). This was paralleled by the EAI
      improvement and by the rates of mucosal healing. Median time to clinical response
      was 5 (IQR 2 to 8) weeks. Bloating was registered in 40% of the patients
      irrespective of the treatment dose. Three of the 10 patients in the 4 g dose
      group reported nausea. CONCLUSION: We found a saturable dose response of rPC in
      the treatment of chronic-active ulcerative colitis with effective doses >or=1 g
      per day; doses of 3 and 4 g seem to be superior in achieving remission.

PMID- 20048684
TI  - Treatment of chronic hepatitis C using a 4-week lead-in with nitazoxanide before
      peginterferon plus nitazoxanide.
AB  - GOALS: The primary aim of this study was to further evaluate the efficacy of
      peginterferon plus nitazoxanide without ribavirin using a 4-week lead-in.
      BACKGROUND: The initial treatment of chronic hepatitis C with nitazoxanide used
      12 weeks of nitazoxanide monotherapy before combination therapy with
      peginterferon with or without ribavirin. STUDY: This open-label pilot study
      enrolled 44 treatment-naive patients with chronic hepatitis C (40 with genotype
      4; 3 with genotype 1; and 1 with genotype 2). The patients received oral
      nitazoxanide 500 mg twice daily for 4 weeks followed by nitazoxanide plus
      peginterferon alfa-2a 180 mug weekly for 36 weeks and were then followed for 24
      weeks. The results of this study were compared with those from an overlapping
      historical trial using 12 weeks of nitazoxanide lead-in. RESULTS: A sustained
      virologic response (SVR) was achieved in 80% of patients, which was similar to
      the SVR rates in the historical trial, that is, 79% and 61% in patients treated
      with and without ribavirin, respectively. A rapid virologic response occurred in
      59% of patients, which was also similar to the rapid virologic response rates in
      the historical trial (64% and 54% in patients treated with and without ribavirin,
      respectively). All 4 patients with genotypes 1 and 2 had an SVR. CONCLUSIONS: The
      nitazoxanide lead-in phase before combination therapy with peginterferon can
      likely be reduced from 12 weeks to 4 weeks without compromising virologic
      response rates. In addition, treatment of chronic hepatitis C with peginterferon
      plus nitazoxanide without ribavirin is promising and requires further study.

PMID- 20048685
TI  - Transarterial chemoembolization in patients with hepatocellular carcinoma and
      renal insufficiency.
AB  - BACKGROUND: Renal dysfunction is often present in patients with cirrhosis and
      hepatocellular carcinoma (HCC). Acute renal failure (ARF) may occur after
      transarterial chemoembolization (TACE) owing to radiocontrast agent. This study
      investigated the incidence and risk factors of ARF and prognostic predictors in
      HCC patients with preexisting renal insufficiency undergoing TACE. METHODS: A
      total of 566 HCC patients undergoing TACE were enrolled. Renal insufficiency was
      defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m.
      RESULTS: In a mean follow-up duration of 18+/-16 months, 231 (40.8%) patients
      undergoing TACE died. Renal insufficiency that was present in 134 (23.7%)
      patients at baseline, independently predicted a poor prognosis in the Cox
      proportional hazards model [risk ratio (RR): 1.47, P=0.012]. Of them, 13 (10%)
      and 6 (5%) patients had transient and prolonged ARF after TACE, respectively.
      Post-TACE gastrointestinal bleeding [odds ratio (OR): 16.54, P=0.001] and higher
      Cancer of the Liver Italian Program (CLIP) scores (> or =2; OR: 4.22, P=0.02)
      were independent risk factors for ARF in the multivariate logistic regression
      analysis. In the Cox model, prolonged ARF (RR: 3.28, P<0.001) and higher CLIP
      scores (> or =2; RR: 2.13, P<0.001) were independent poor prognostic predictors
      for HCC patients with renal insufficiency receiving TACE. CONCLUSIONS:
      Gastrointestinal bleeding and higher CLIP scores are associated with the
      development of ARF in patients with HCC and renal insufficiency undergoing TACE.
      Higher CLIP scores and renal insufficiency, either preexisting before TACE or as
      a complication of TACE, are poor prognostic predictors in HCC patients receiving
      TACE.

PMID- 20048686
TI  - Platelet indices are not suitable for screening of leukemia.

PMID- 20048687
TI  - Acute promyelocytic leukemia treated with idarubicin complicated by focal
      segmental glomerulosclerosis.
AB  - The authors report a 9-year-old boy presenting with a left cerebral ischemic
      infarction as the first manifestation of acute promyelocytic leukemia. During
      consolidation chemotherapy, the patient developed nephrotic syndrome and a renal
      biopsy revealed focal segmental glomerulosclerosis (FSGS). Remission in bone
      marrow was achieved with chemotherapy, however, new intracranial ischemic areas
      developed on follow-up. Acute promyelocytic leukemia complicated by FSGS has not
      been previously reported in children. There may be a relationship between
      anthracycline treatment and FSGS. Thrombosis could be related with both leukemia
      and nephrotic syndrome, here thrombosis was the initial symptom, before FSGS was
      diagnosed.

PMID- 20048688
TI  - INI1 (BAF 47) immunohistochemistry is an essential diagnostic tool for children
      with hepatic tumors and low alpha fetoprotein.
AB  - Malignant rhabdoid tumor (MRT) of the liver is a rare malignancy with grave
      prognosis. This entity should be considered in the differential diagnosis of any
      aggressive liver tumor with low levels of alpha fetoprotein. We report 2 cases of
      hepatic MRT presenting in infancy. In these 2 cases, we show that loss of INI1
      facilitates making the correct diagnosis of primary hepatic MRT utilizing BAF 47
      (INI1 gene product) immunostains. Difficulty encountered in making this rare
      diagnosis, including the need for repeated biopsies, can be avoided if MRT is
      considered in the differential diagnosis early on and BAF 47 immunohistochemistry
      is ordered.

PMID- 20048689
TI  - Isolated renal relapse in acute lymphoblastic leukemia.
AB  - Current therapy for acute lymphoblastic leukemia have resulted in cure rates over
      80%. Relapses occur most frequently in the bone marrow. We report the unusual
      case of a young man who presented with an isolated kidney relapse after
      maintaining remission from acute lymphoblastic leukemia for over 6 years. Sites
      of extramedullary relapse and a review of the literature are discussed.

PMID- 20048690
TI  - The critically ill child with novel H1N1 influenza A: a case series.
AB  - OBJECTIVE: To describe the presentation, course, and outcome of critically ill
      children with novel H1N1 influenza disease. DESIGN: Retrospective case series.
      SETTING: Pediatric intensive care unit in an urban tertiary academic center.
      PATIENTS: Thirteen consecutive patients admitted between June 2009 and August
      2009 and known or subsequently found to be infected with novel H1N1 influenza A.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, laboratory, and
      radiographic data were reviewed. The patients were predominantly male (62%), aged
      5 months to 21 yrs, and most (92%) had known risk factors for severe disease.
      Direct fluorescent antibody testing had a high false-negative rate (62%) and
      delayed treatment in some cases. The respiratory illness presented clinically
      with both bronchoconstriction and alveolar consolidation to varying degrees.
      Bacterial superinfection occurred frequently (23%). Forty-six percent of patients
      required mechanical ventilation and 23% required inotropic support for
      hypotension. None of the patients in this series required extracorporeal membrane
      oxygenation. Intensive care unit length of stay did not differ between an early
      (within 48 hrs) oseltamivir treatment group (length of stay, 4.2 +/- 4.4 days)
      vs. a late treatment group (length of stay, 6.8 +/- 8.8 days). All patients
      survived to hospital discharge. CONCLUSIONS: Underlying chronic illness
      (especially respiratory illness) seems associated with critical novel H1N1
      influenza disease in children. Respiratory manifestations are highly variable
      among patients and within a single patient involving both bronchoconstriction and
      alveolar disease. Therapies must be individualized and rapidly adjusted. The
      duration of critical illness was not different between early and late treatment
      groups. Whether this is reflective of sample size or indicative of the importance
      of therapeutic intervention at any time early during infection in critically ill
      patients is unclear. Bacterial superinfection was more common than previously
      reported for seasonal influenza A. Moderate novel H1N1 influenza disease,
      including respiratory failure and hypotension, had 100% survival in our series.

PMID- 20048691
TI  - Prospective study on the outcome of patients with hepatocellular carcinoma
      registered for living donor liver transplantation: how long can they wait?
AB  - BACKGROUND.: In countries where cadaveric organ donation is limited, living donor
      liver transplantation (LDLT) has been reserved as a rescue option for the
      patients with uncontrollable hepatocellular carcinoma (HCC). PATIENTS AND
      METHODS.: Between March 2002 and June 2006, 56 patients with HCC had been
      registered as a LDLT candidate after HCC cannot be treated conventionally. We
      compared the survival rates between the patients who underwent LDLT (living donor
      liver transplantation group: LT, n=29) and those who did not undergo LDLT (no
      transplantation group: NLT, n=27). In the NLT group, we examined the periods
      suitable for resection or ablation (from first diagnosis to registration),
      suitable for LDLT, and unsuitable for LDLT. RESULTS.: Even among the patients who
      did not meet Milan criteria (LT: n=10, NLT: n=16), 1- and 3-year survival rates
      were significantly higher in the LT group than in the NLT group: 90.0% and 60.0%
      vs. 75.0% and 8.3%, respectively (P=0.046). In the NLT group, the median periods
      suitable for resection or ablation, suitable for LDLT, and unsuitable for LDLT
      were 28.9, 12.2, and 3.5 months, respectively. CONCLUSIONS.: LDLT is acceptable
      for the patients who gave up the conventional treatment. Approximately 12 months
      remain for the LDLT candidates with HCC to decide to undergo it.

PMID- 20048692
TI  - First report on a series of HIV patients undergoing rapamycin monotherapy after
      liver transplantation.
AB  - INTRODUCTION: Some experimental trials have demonstrated that rapamycin (RAPA) is
      able to inhibit HIV-1 progression in three different ways: (1) reducing CCR5-gene
      transcription, (2) blocking interleukin-2 intracellular secondary messenger
      (mammalian target of rapamycin), and (3) up-regulating the beta-chemokine
      macrophage inflammatory protein (MIP; MIP-1alpha and MIP-1beta). We present the
      preliminary results of a prospective nonrandomized trial concerning the first HIV
      patient series receiving RAPA monotherapy after liver transplantation (LT).
      METHODS: Since June 2003, 14 HIV patients have received cadaveric donor LT due to
      end-stage liver disease (ESLD) associated or not associated with hepatocellular
      carcinoma, scored by the model for ESLD system. Patients were assessed using the
      following criteria for HIV characterization: CD4 T-cell count more than 100/mL
      and HIV-RNA levels less than 50 copies/mL. Primary immunosuppression was based on
      calcineurin inhibitors (CI), whereas switch to RAPA monotherapy occurred in cases
      of CI complications or Kaposi's sarcoma. RESULTS: Mean overall post-LT follow-up
      was 14.8 months (range: 0.5-52.6). Six of 14 patients were administered RAPA
      monotherapy. Mean preswitch period from CI to RAPA was 67 days (range: 10-225
      days). Mean postswitch follow-up was 11.9 months (range: 2-31 months). All
      patients were affected by ESLD, which was associated with hepatocellular
      carcinoma in seven patients. ESLD occurred due to hepatitis C virus (HCV)-related
      hepatopathy for nine patients, hepatitis B virus-related hepatopathy for one
      patient, and hepatitis B virus-HCV hepatopathy for four patients. Significantly
      better control of HIV and HCV replication was found among patients taking RAPA
      monotherapy (P=0.0001 and 0.03, respectively). CONCLUSIONS: After in vitro and in
      vivo experimental evidence of RAPA antiviral proprieties, to our knowledge, this
      is the first clinical report of several significant benefits in long-term
      immunosuppression maintenance and HIV-1 control among HIV positive patients who
      underwent LT.

PMID- 20048693
TI  - Intramedullary cavity as an implant site for bioartificial pancreas: an in vivo
      study on diabetic canine.
AB  - BACKGROUND: Fibrous tissue outgrowth and hypoxia are the major restrictions for
      the application of bioartificial pancreas (BAP). Accordingly, the intramedullary
      cavity is proposed as an implant site, and a BAP constructed of calcium phosphate
      cement chamber was implanted. METHODS: Mouse insulinoma cells were encapsulated
      in agarose gel and then enclosed in a calcium phosphate cement chamber to
      fabricate a BAP. BAPs were implanted in the femoral intramedullary cavity of
      diabetic dogs. Pre- and postprandial blood glucose levels were monitored
      perioperatively. Blood samples were collected for the analysis of C-peptide
      level, and physiological conditions were observed at predetermined intervals.
      BAPs were retrieved at 12 weeks postoperatively for histologic examination.
      RESULTS: Preprandial blood glucose level of diabetic dogs decreased from 420 +/-
      25 to 223 +/- 47 mg/dL at 1 day postoperatively and was maintained in the range
      of 259 +/- 36 mg/dL for 12 weeks. As serum C-peptide level increased from 5.3 +/-
      2.8 to 105.7 +/- 19.4 pmol/L, the rate of decrease of postprandial blood glucose
      was accelerated. Histologic examination revealed that recipient bone tissues were
      binding to the surfaces of BAPs directly; there was no development of fibrous
      tissue. Immunohistochemical stain was positive for insulin in the enclosed
      insulinoma cells. CONCLUSIONS: This study demonstrated that BAPs implanted into
      the intramedullary cavity functioned well during the experimental period. Thus,
      the intramedullary cavity can serve as an implant site for BAPs.

PMID- 20048694
TI  - Are B cells agreeable to veto?

PMID- 20048695
TI  - Reduction in cardiovascular death after kidney transplantation.
AB  - BACKGROUND: Cardiovascular (CVS) disease is the commonest cause of death after
      kidney transplantation. In the general population, CVS mortality has reduced
      significantly over the last two decades; however, this trend has not been
      specifically examined in the kidney transplant population. METHODS: We studied
      all patients in Australia and New Zealand with a functioning kidney transplant
      between 1980 and 2007 and examined trends in the cause and timing of all 2195
      deaths recorded after kidney transplantation in the Australia and New Zealand
      Dialysis and Transplant registry. Poisson regression was used to compare death
      rates over the time periods. RESULTS: CVS events were the commonest cause of
      death throughout all the time points examined; however, CVS death rates
      significantly decreased with an adjusted risk ratio of 0.61 (95% confidence
      interval, 0.38-0.96; P=0.034) for 2005 to 2007 era. In comparison, death rates
      due to malignancy have increased significantly over this period. Decreased CVS
      death rates have occurred despite increasing comorbidity at the time of
      transplantation. Factors associated with CVS death were older recipient age,
      preexisting CVS disease, and diabetes mellitus. There was a significantly lower
      CVS death rate in patients with a glomerular filtration rate >48 mL/min compared
      with those with poor renal function (risk ratio, 0.66; 95% confidence interval,
      0.45-0.95; P=0.024). CONCLUSIONS: These trends suggest improvements in CVS risk
      management and outcomes in the kidney transplant population in Australia and New
      Zealand.

PMID- 20048696
TI  - Neutralizing antibodies against HIV-1: can we elicit them with vaccines and how
      much do we need?
AB  - PURPOSE OF REVIEW: This review describes some of the major obstacles that have
      impeded progress in the development of an effective neutralizing antibody-based
      HIV-1 vaccine and explains why it may be possible to overcome these obstacles. A
      renewed interest in the B-cell response in HIV-1-infected individuals is
      emphasized. RECENT FINDINGS: New assay technologies and access to large numbers
      of clinical specimens have permitted a detailed assessment of the neutralizing
      antibody response in HIV-1-infected individuals. Recent studies have demonstrated
      that B cells can be stimulated to generate high titers of broadly cross-reactive
      neutralizing antibodies against multiple genetic subtypes of the virus.
      Preliminary evidence suggests that some of these antibodies are directed against
      epitopes in the CD4 binding site on monomeric gp120, whereas many others are
      directed against epitopes that remain to be identified. SUMMARY: The rationale
      for pursuing an effective neutralizing antibody-based HIV-1 vaccine is
      strengthened by the recent demonstration of potent neutralizing antibody
      responses in a subset of HIV-1-infected individuals. Information on how this
      response develops and what epitopes are targeted could provide the insights that
      are needed to design improved vaccine strategies.

PMID- 20048697
TI  - Genetic and antigenic features of the transmitted virus.
AB  - PURPOSE OF REVIEW: Methodological and analytical advances in obtaining genetic
      information during acute HIV infection have provided an unprecedented view into
      viral transmission and early immune evasion. The findings suggest that a better
      understanding of the restricted viral diversity that follows mucosal transmission
      could lead to novel strategies for vaccine, microbicide or other therapeutic
      interventions. RECENT FINDINGS: During sexual transmission of HIV-1, viral
      diversity is reduced presumably due to obstacles an infectious virion must
      overcome to establish infection within a new host. Recently, single-genome
      amplification followed by direct sequencing from samples obtained during acute
      infection has been utilized to quantify the actual number of infecting variants.
      Overall, the vast majority (over 75%) of new infections were initiated by a
      single genetic variant. Transmission of multiple variants from a single donor
      (between two and five) was also observed and is associated with factors that
      compromise the genital mucosa. These analyses included over 200 patients
      representing subtypes A, B, C, D and have been reproduced in nonhuman primate
      model systems. SUMMARY: During acute infection, there is limited viral diversity
      in most patients, which provides a window of opportunity for vaccines or
      therapies to inhibit or prevent infection. Identifying the common genetic and
      antigenic properties of newly transmitted viruses will be necessary to advance
      vaccine design.

PMID- 20048698
TI  - Specificity of the autologous neutralizing antibody response.
AB  - PURPOSE OF REVIEW: It has long been known that autologous neutralizing antibodies
      (AnAbs) exert pressure on the envelope of HIV, resulting in neutralization
      escape. However, recently, progress has been made in uncovering the precise
      targets of these potent early antibodies. RECENT FINDINGS: AnAbs primarily target
      variable regions of the HIV-1 envelope, explaining the strain-specificity of
      these antibodies. Despite high neutralizing potential and cross-reactivity, anti
      V3 antibodies do not contribute to autologous neutralization. The V1V2 is
      commonly immunogenic in early HIV-1 and simian human immunodeficiency virus
      infections, though the nature of these epitopes remains to be determined. In
      subtype C viruses, the C3 region is a neutralization target, possibly as a result
      of its more exposed and amphipathic structure. Autologous neutralization appears
      to be mediated by very few AnAb specificities that develop sequentially
      suggesting the possibility of immunological hierarchies for both binding and
      neutralizing antibodies. The role of AnAbs in preventing superinfection and in
      restricting virus replication is reexamined in the context of recent data.
      SUMMARY: New studies have greatly contributed toward our understanding of the
      specificities mediating autologous neutralization and highlighted potential
      vulnerabilities on transmitted viruses. However, the contribution of AnAbs to the
      development of neutralization breadth remains to be characterized.

PMID- 20048699
TI  - Specificities of broadly neutralizing anti-HIV-1 sera.
AB  - PURPOSE OF REVIEW: Effective vaccine-elicited immunity against HIV-1 infection
      will likely require broadly neutralizing antibodies to interrupt the fusion
      promoting functions of the viral envelope glycoprotein spikes. Efforts in this
      area have, however, been fraught with challenges. The handful of existing broadly
      neutralizing monoclonal antibodies has provided information on some of the virus'
      sites of vulnerability, fueling a decade of structure-informed vaccine design.
      The fact that very few bnmAbs have been recovered to date illustrates the poor
      immunogenicity of these epitopes. Recognizing that progress may require more
      basic information, there has been a notable shift in the field toward identifying
      new chinks in HIV-1's armor. These efforts are based on the observation that some
      infected patients develop exceptionally broad serum neutralizing antibodies
      responses, a better understanding of which would be valuable for vaccine efforts
      aimed at eliciting similar specificities. RECENT FINDINGS: New mapping
      methodologies are now providing an appreciation of the incidence of specificities
      similar to the existing known bnmAbs as well as some intriguing insights into
      novel specificities. SUMMARY: The new information emerging from mapping efforts
      should help to sharpen efforts to isolate new bnmAbs and moreover, may provide
      crucial information for the rational design of novel vaccine candidates.

PMID- 20048700
TI  - HIV-1-specific antibody responses during acute and chronic HIV-1 infection.
AB  - PURPOSE OF REVIEW: The humoral immune response to HIV-1 throughout infection is
      comprised of complex mixtures of antibody isotypes with numerous HIV-1
      specificities. However, unlike antibody responses to most infections, protective
      antibody responses are delayed and do not arise until long after HIV-1 latency is
      established. We review recent data on HIV-1-specific antibody isotypes induced
      following HIV-1 transmission: to understand the effects of HIV-1 on B cell and T
      cell effector responses, to understand the timing of the rise and fall of
      different anti-HIV-1 antibodies and to understand how antibodies could contribute
      to protective immunity if they were either pre-existing or elicited immediately
      after HIV-1 transmission. RECENT FINDINGS: Studies of the earliest events
      following infection by the transmitted/founder virus have recently revealed that
      early destruction of B cell generative microenvironments may be responsible for
      delay of potentially protective anti-HIV-1 antibody responses. Unlike the initial
      CD8 T cell response to HIV-1, the initial induced antibody response is usually
      ineffective in controlling virus replication during acute HIV-1 infection.
      SUMMARY: The antibody isotypes and specificities elicited during HIV-1 infection
      can provide a window into deciphering the detrimental effects of HIV-1 on B cell
      and T cell responses. Additionally, further characterization of the virus
      inhibitory capabilities of anti-HIV-1 antibody isotypes can define the spectrum
      of potential protective HIV-1 antibodies that could be readily elicited by
      experimental vaccines and adjuvants.

PMID- 20048701
TI  - Immunogenicity of HIV-1 envelope glycoprotein oligomers.
AB  - PURPOSE OF REVIEW: We summarize and discuss recent developments regarding the
      immunogenicity of human immunodeficiency virus type 1 (HIV-1) envelope
      glycoprotein (Env) oligomers, focusing, for the most part, on trimeric,
      recombinant protein immunogens. RECENT FINDINGS: The three-dimensional cryo
      electron tomography images of the HIV-1 Env trimeric spike, coupled with previous
      data demonstrating the impact on envelope glycoprotein (gp120)-transmembrane
      glycoprotein (gp41) cleavage of the architecture of the Env trimers, provide
      exciting information that may lead to new avenues for novel immunogen design.
      Through new processes to map region-specific anti-Env antibodies present in
      immune serum, it is now possible to define antibody specificities against
      conformationally sensitive surfaces of Env. A number of strategies designed to
      counteract the immunodominance of the HIV-1 Env variable regions were attempted,
      and a recent study demonstrates that immunization with Env trimers provides
      sterilizing protection against mucosal challenge with virus. Importantly,
      protection against the challenge virus was associated with in-vitro HIV-1
      neutralization titers. SUMMARY: Several studies within the past 18 months provide
      exciting structural information and the development of tools that have the
      potential to improve Env trimer design and the analysis of trimer immunogenicity
      studies. The ability to predict protection against a challenge virus through an
      in-vitro neutralization screen may be very helpful for evaluation of immunogens
      to move forward into clinical trials.

PMID- 20048702
TI  - Fc receptor-mediated antiviral antibodies.
AB  - PURPOSE OF REVIEW: We summarize current information on Fc receptor-mediated
      antiviral activities of antibodies. These activities include Fcgamma receptor
      mediated inhibition and neutralization of HIV on antigen-presenting cells,
      antibody-dependent cellular cytotoxicity, and antibody-dependent cell-mediated
      virus inhibition (ADCVI). RECENT FINDINGS: An Fcgamma receptor-mediated mechanism
      that results in augmented neutralization and may render nonneutralizing
      antibodies inhibitory has been demonstrated in antigen-presenting cell. Antibody
      dependent cellular cytotoxicity antibody activity correlates inversely with HIV
      disease progression in humans, and higher vaccine-induced antibody-dependent
      cellular cytotoxicity antibody responses are associated with lower acute simian
      immunodeficiency virus viremia levels in macaques. Following vaccination with
      rgp120, ADCVI antibody levels are higher among those with a lower rate of
      sexually acquired HIV infection. Nonneutralizing simian immunodeficiency virus
      immune serum that prevents infection of newborn macaques after oral challenge has
      potent ADCVI antibody activity. Abrogating the ability of the Fc segment of the
      broadly neutralizing mAb b12 to bind to Fcgamma receptors and to mediate ADCVI
      substantially reduces b12's protective effect in a simian/human immunodeficiency
      virus vaginal challenge model. SUMMARY: Fc-FcgammaR interactions play a critical
      role in the biological function of antibody and are likely to be instrumental in
      preventing or modulating lentiviral infection. Exploiting antibody responses that
      depend on Fc-FcgammaR interactions may help widen the breadth and increase the
      potency of vaccine-induced antibody. Although the importance of generating
      optimal Fab-antigen interactions cannot be overestimated, improving Fc-FcgammaR
      interactions through adjuvants or other strategies provides another option for
      improving HIV vaccines and immunotherapies.

PMID- 20048703
TI  - Complement, Fc receptors and antibodies: a Trojan horse in HIV infection?
AB  - PURPOSE OF REVIEW: Because complement is present in all fluids of the body,
      including serum, saliva and seminal fluid, and is found at mucosal surfaces and
      in the brain, all pathogens have to deal with complement proteins. Thus,
      immediately upon entering the host, independent on the route of infection, HIV
      activates the complement system. Although a first line of immune defense,
      complement cannot eliminate retroviral infections completely. RECENT FINDINGS:
      Recent data indicate that complement, in concert with non-neutralizing
      antibodies, contributes to the control of HIV replication at early stages of
      infection. In parallel or at later stages, complement and non-neutralizing
      antibodies may counteract the immune response by enhancing HIV infection via
      complement and Fc-receptor-positive cells in 'cis' and 'trans'. SUMMARY: This
      review highlights current knowledge in this field and emphasizes the contribution
      of complement and non-neutralizing antibodies in controlling versus and enhancing
      infection.

PMID- 20048704
TI  - Impact of host cell variation on the neutralization of HIV-1 in vitro.
AB  - PURPOSE OF REVIEW: In this review we present current advances in our
      understanding of HIV-1 neutralization assays that employ primary cell types, as
      compared with those that utilize cell lines and the newer, more standardized
      pseudovirus assays. A commentary on the challenges of standardizing in-vitro
      neutralization assays using primary cells is included. RECENT FINDINGS: The data
      from reporter cell line neutralization assays may agree with results observed in
      primary cells; however, exceptions have recently been reported. Multiple
      variables exist in primary cell assays using peripheral blood mononuclear cells
      from HIV-seronegative donors; in-vitro neutralization titers can vary
      significantly based on the donor cells used for assay targets and for virus
      propagation. Thus, more research is required to achieve validated primary cell
      neutralization assays. SUMMARY: HIV-vaccine-induced antibody performance in the
      current neutralization assays may function as a 'gatekeeper' for HIV-1 subunit
      vaccine advancement. Development of standardized platforms for reproducible
      measurement of in-vitro neutralization is therefore a high priority. Given the
      considerable variation in results obtained from some widely applied HIV
      neutralization platforms, parallel evaluation of new antibodies using different
      host cells for assay targets, as well as virus propagation, is recommended until
      immune correlates of protection are identified.

PMID- 20048705
TI  - The implications of patterns in HIV diversity for neutralizing antibody induction
      and susceptibility.
AB  - PURPOSE OF REVIEW: Designing an HIV vaccine capable of eliciting broadly cross
      reactive neutralizing antibodies is an extraordinarily difficult challenge. Here
      we focus on the implications of HIV diversity for vaccine design, detailing the
      impact of levels of variation in epitopes of known potent neutralizing
      antibodies, and summarizing patterns of overall variation in regional domains
      within gp120. Strategies for rational vaccine design, to enhance coverage of
      HIV's natural diversity, are considered. RECENT FINDINGS: Each amino acid in an
      envelope gp120 three-dimensional structure was grouped with its 10 nearest
      neighbors and classified by their natural sequence variability. Within-subtype
      variation is superimposed on patterns of subtype-specific variation. Regions
      under selection with moderate diversity are realistic vaccine targets; their
      variation reflects the value of escape in these regions, whereas the level of
      diversity is potentially approachable with a vaccine. SUMMARY: HIV diversity is
      so extensive that vaccine design strategies may benefit by factoring in diversity
      from the earliest stages, even for vaccines that target relatively conserved
      regions.

PMID- 20048706
TI  - New virologic reagents for neutralizing antibody assays.
AB  - PURPOSE OF REVIEW: This review summarizes current and novel virologic reagents
      employed for the development and application of in-vitro assays that assess
      neutralizing activity of antibodies against HIV-1. Characteristics of several
      virologic approaches are placed in context with various cellular targets and
      assay read-outs intended to determine potency and breadth of neutralization in
      patient cohorts and clinical vaccine trials. RECENT FINDINGS: New molecular
      virologic reagents developed for in-vitro primary cell-based assays promise to
      facilitate rigorous and standardized assessment of anti-HIV-1-neutralizing
      antibody responses elicited by vaccine immunogens. SUMMARY: Comprehensive
      assessment of anti-HIV-1 antibody potency and breadth is essential for evaluating
      vaccine immunogens, the advancement of vaccine candidates into clinical trials,
      and ultimately the development of effective vaccine strategies. Env-pseudovirion
      and recombinant reporter cell line neutralization assays are important tools for
      rapid and standardized measurement of neutralizing antibody activity. However,
      recent studies indicate that reporter cell lines fail to detect neutralization
      activity of certain antibodies observed when analyzed in peripheral blood
      mononuclear cells and may yield results on neutralizing antibody breadth that are
      discordant with peripheral blood mononuclear cell assays. Importantly, it remains
      unknown whether current in-vitro assays may be predictive of a protective
      neutralizing antibody response elicited by vaccine immunogens. This situation
      underscores the significance of standardizing existing, complementary methods as
      well as developing new assay concepts that assess neutralization in primary
      cells. Thus, this chapter focuses on new virologic reagents that promise to
      facilitate reaching this goal.

PMID- 20048707
TI  - Antibody-secreting B cells in HIV infection.
AB  - PURPOSE OF REVIEW: Several recent advances are permitting a detailed examination
      of the HIV-specific B-cell response. In this review, we summarize these advances
      and their implications for understanding the response to HIV during chronic
      infection or in vaccine. RECENT FINDINGS: In HIV-infected patients, aberrant B
      cell phenotypes have been associated with diminished humoral responses to other
      pathogens. HIV-specific B cells are overrepresented in some of these abnormal
      subsets. Over the past 2 years, flow cytometry-based techniques have been
      developed to stain HIV-specific B cells. These techniques are permitting a re
      examination of frequency, phenotype, and function of HIV-specific B cells. They
      are also permitting the isolation of HIV-specific B cells in high purity.
      Immunoglobulin G from sorted HIV-specific B cells is oligoclonal, uses a limited
      repertoire of immunoglobulin genes, and targets multiple epitopes on Env.
      SUMMARY: It is likely that the defects found in total B cells in HIV-infected
      patients also play a role in the poorly effective HIV-specific antibody response.
      A subset of HIV-infected patients produced broadly neutralizing antibodies.
      Understanding this antibody response, and the B cells that underlie it, may be
      critical in efforts to elicit neutralizing antibodies against HIV.

PMID- 20048708
TI  - Challenges for structure-based HIV vaccine design.
AB  - PURPOSE OF REVIEW: We review structural information on the native HIV envelope
      trimer and the known epitopes for broadly neutralizing antibodies and discuss how
      this structural information should guide the design of more effective immunogens.
      RECENT FINDINGS: Recent epitope mapping of HIV-positive sera demonstrates that
      the immune system is able to mount a potent and broadly neutralizing antibody
      response against conserved elements of the HIV envelope. The structure of
      trimeric envelope spikes on intact HIV-1 virions (the target of neutralizing
      antibodies) was determined at low resolution using cryo-electron tomography.
      Fitting high-resolution crystal structures of monomeric gp120 complexed with
      different neutralizing ligands into the cryo-electron density maps provides
      useful models for the native virion trimer and for mechanisms of neutralization.
      SUMMARY: So far, all attempts to elicit broadly neutralizing antibodies against
      HIV by immunization have failed. Recent structural information on the virion
      associated HIV envelope spike and of the precise interaction of broadly
      neutralizing mAbs with their epitopes clarifies the steric and geometric
      constraints faced by antibodies targeting conserved HIV epitopes. Implications
      for vaccine design are discussed.

PMID- 20048709
TI  - Novel adjuvants for B cell immune responses.
AB  - PURPOSE OF REVIEW: To summarize recent progress in the development of adjuvants
      with a special focus on adjuvants that enhance B-cell responses to protein-based
      vaccines. Both established and new experimental approaches are described and also
      briefly we discuss how adjuvants and virus-based vaccines interact with the
      immune system. RECENT FINDINGS: Two new adjuvants were recently approved for
      human applications and many others are in preclinical or clinical testing.
      Significant advances were made to describe the mechanism of action of adjuvants.
      For example, aluminum hydroxide salts were shown to engage Nalp3, a member of the
      cytosolic NOD-like receptors and activation of B cells via invariant natural
      killer cell presentation of alpha-galactosylceramide was described. The effects
      of Toll-like receptor ligands on B-cell differentiation were further
      characterized and a peptide derived from IPS-1, a cytosolic signaling molecule,
      was shown to provide adjuvant effect. Stimulation of protective antibodies
      against HIV-1 may require extensive antibody affinity maturation, thus long-term
      exposure or repeated administration of antigen may be needed to induce effective
      B-cell responses. SUMMARY: Advances in our understanding of how specific
      signaling pathways link innate and adaptive immunity provides a basis for the
      design of improved adjuvants to promote broad and potent B-cell responses.

PMID- 20048710
TI  - Neurological disease: the effects of HIV and antiretroviral therapy and the
      implications for early antiretroviral therapy initiation.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine the literature
      regarding HIV-associated neurocognitive disorders, early HIV infection of the
      central nervous system (CNS), the role of the peripheral immune system in
      controlling HIV infection and disease within the brain and the potential role
      that early antiretroviral treatment may play in the preservation of
      neurocognitive health in patients with more than 500 CD4+ cells/microl. RECENT
      FINDINGS: In the post highly active antiretroviral therapy (HAART) era, HIV
      associated neurocognitive disorders remain prevalent and even mild-moderate
      immunosuppression carries a risk for the development of HIV-associated dementia.
      HIV infection of the CNS occurs early in the illness, and data suggest that a
      robust peripheral immune system is key to the long-term control of CNS HIV
      infection. HAART results in clinical, neuropsychological and neuroradiological
      improvement in patients with HIV-associated neurocognitive disorders, and the
      prescription of HAART regimens with good cerebrospinal fluid penetration appears
      to be preferable in this setting. There is little evidence that HAART causes CNS
      toxicity. The benefits and risks of HAART in the preservation or enhancement of
      neurocognitive function in well, HIV-infected patients with more than 500 CD4+
      cells/microl are unknown. SUMMARY: The prescription of HAART in well, HIV
      infected patients with high CD4+ cell counts may afford enhanced control of CNS
      HIV infection as a result of the benefits of HAART upon peripheral immune
      function. In turn, this may result in superior or preserved neurocognitive
      performance in comparison to the current practice of commencing HAART when CD4+
      cells reach 350 cells/microl or lower. This hypothesis will be tested in an
      upcoming randomized clinical trial.

PMID- 20048712
TI  - Epidemiology of treatment failure: a focus on recent trends.
AB  - PURPOSE OF REVIEW: As antiretroviral therapy has been refined with the
      development of more potent agents and simpler regimens, fewer individuals
      experience treatment failure. This review will highlight recent trends in
      treatment failure and virologic resistance in the developed world and resource
      limited settings. RECENT FINDINGS: The goal of antiretroviral therapy in all
      individuals, regardless of prior treatment exposure or HIV drug resistance, is to
      achieve full suppression of viral replication with a viral load of less than 50
      copies/ml. This goal has been made a reality by the development of newer agents
      and simpler, better tolerated regimens. Recent cohort studies have demonstrated
      improved virologic outcomes in the current antiretroviral era, with decreased
      rates of virologic failure and associated resistance. Improved tolerability has
      aided adherence, which remains a key determinant of treatment success. Cohorts in
      resource-limited settings report improved clinical and virologic outcomes as
      rollout of highly active antiretroviral therapy programs continues. SUMMARY:
      There has been a reassuring decrease in the frequency of virological failure and
      drug resistance in the modern highly active antiretroviral therapy era. This
      observation provides an important incentive to strengthen support of
      antiretroviral therapy programs to optimize virological outcomes, particularly in
      resource-limited settings in which access to newer agents and laboratory
      monitoring may be needed to ensure sustainable success.

PMID- 20048711
TI  - Defining treatment failure in resource-rich settings.
AB  - PURPOSE OF REVIEW: To define treatment failure in resource-rich settings;
      summarizing current guidelines, assays, the significance of detectable viremia,
      and definitions of treatment failure in clinical and research settings. RECENT
      FINDINGS: The goal of treatment should be full viral suppression, even in highly
      treatment-experienced patients. SUMMARY: Treatment failure is defined as repeated
      HIV RNA values above the lower limit of detection of a sensitive assay (usually
      50 copies/ml). This criterion is based on evidence that the maximum clinical
      benefit of antiretroviral therapy is derived by keeping the viral load as low as
      possible. Full viral suppression should be achievable in all patients, both
      treatment-naive and experienced. Transient, low-detectable viremia ('blips') may
      not predict virologic breakthrough. However, consecutive or higher-level
      transient viremia is associated with risk of treatment failure. Defining failure
      by a confirmed HIV RNA more than 50 copies/ml is the most conservative approach,
      but the use of such low limits of detection in clinical trials may lead to a high
      false-positive 'failure' rate, thus a definition of 200 copies/ml may be
      preferable. Variation in clinical trial endpoint definitions creates a challenge
      for comparing results between studies. For example, using a composite endpoint to
      define treatment failure may result in a high proportion of 'failures' that are
      not related to poor virologic response.

PMID- 20048713
TI  - The use of resistance testing in the management of HIV-1-infected patients.
AB  - PURPOSE OF REVIEW: Resistance testing has become an important component of the
      recommended care for treatment-naive and treatment-experienced HIV-infected
      patients in the developed world, and their use has been shown to improve clinical
      outcomes. Despite the widespread use of resistance testing, the clinician faces a
      number of challenges in optimally applying these technologies to antiretroviral
      management. RECENT FINDINGS: Even with the aid of a genotypic interpretation
      system, the interpretation of a genotype is complex and benefits from expert
      input. Phenotypic resistance testing is limited by cost and availability for many
      patients. Standard resistance testing (both genotypes and phenotypes) is unable
      to detect minority species. The presence of resistant minority populations has
      been associated with virologic failure. However, the current techniques available
      to detect their presence are cumbersome and not soon likely to become part of
      routine clinical care. The development of the chemokine (C-C motif) receptor 5
      antagonists has provided new challenges in quantifying antiretroviral resistance.
      SUMMARY: Resistance testing plays a central role in the management of treatment
      experienced patients. Further progress in the interpretation of resistance
      testing, especially as new agents are developed, will continue to add value to
      the care of HIV-infected patients.

PMID- 20048715
TI  - Adherence to antiretroviral therapy: the more you look, the more you see.
AB  - PURPOSE OF REVIEW: There is evolving understanding of adherence to antiretroviral
      therapy (ART) and the consequences of nonadherence. The present review aims to
      discuss recent research findings that illuminate lingering clinical questions or
      contribute to the contextual framework for future research. RECENT FINDINGS:
      Although some patients can achieve undetectable viral load at moderate adherence
      levels, studies confirmed that achieving very high adherence optimizes
      virological and clinical outcomes. In computer modeling, earlier initiation of
      ART despite suboptimal adherence was associated with improved survival and
      quality-adjusted life years. Better adherence and virological outcomes occurred
      when ART was initiated during hospitalization versus outpatient setting, and when
      depressed patients were treated with selective serotonin reuptake inhibitors.
      Differential adherence to individual drugs in an antiretroviral regimen appears
      to be common. Preliminary data from randomized studies designed to evaluate
      patient-selected treatment partners showed no clear benefit on long-term viral
      suppression. SUMMARY: Earlier initiation of ART may be desirable even in some
      patients with suboptimal adherence. Adherence should be reinforced during periods
      of viral suppression, maximum adherence should be targeted, and attention paid to
      differential adherence and treatment of depression.

PMID- 20048714
TI  - Tropism testing in the clinical management of HIV-1 infection.
AB  - PURPOSE OF REVIEW: A variety of methods are available to determine HIV-1 co
      receptor usage, commonly referred to as viral tropism. This article reviews
      recent data on phenotypic and genotypic assays of HIV-1 tropism. RECENT FINDINGS:
      Tropism assays are used to determine co-receptor usage of HIV-1 in patients who
      may be candidates for treatment with CCR5 antagonists. Phenotypic assays are used
      most often in the clinical trials of CCR5 antagonists, and are considered the
      'gold standard' for comparison with other methods of tropism testing.
      Enhancements have allowed detection of a lower threshold of minor CXCR4-using
      species. When compared with phenotypic assays, genotypic methods have poor
      sensitivity but good specificity at detecting CXCR4-using HIV-1. Preliminary
      results from a recent comparative study suggest that some genotypic methods may
      perform as well as phenotypic tests in predicting virologic response to CCR5
      antagonists. Several studies show that tropism testing may provide useful
      prognostic information regarding the risk of disease progression. SUMMARY:
      Understanding the characteristic of different tropism assays is important for
      their clinical use. Although phenotypic testing currently is favored, genotypic
      assays may be a suitable alternative in appropriate settings.

PMID- 20048716
TI  - First-line regimen failure of antiretroviral therapy: a clinical and evidence
      based approach.
AB  - PURPOSE OF REVIEW: To provide a clinical approach for choosing an appropriate
      second-line antiretroviral (ARV) regimen in HIV-positive patients with virologic
      failure. RECENT FINDINGS: Patients should be carefully evaluated as to why
      failure occurred and undergo HIV resistance testing to guide second-line
      treatment options. The new regimen should be initiated as soon as possible to
      avoid evolution of resistance. There is a paucity of clinical trial data to make
      recommendations for optimal second-line regimens. With failure, a member of the
      alternative class nonnucleoside reverse transcriptase inhibitor or ritonavir
      protease inhibitor] is traditionally combined with two active nucleoside reverse
      transcriptase inhibitors. Etravirine may be effective, if adequately supported,
      depending upon the resistance profile. If protease inhibitor resistance is
      detected, second-generation agents such as darunavir/r or tipranavir/r are
      preferred. Integrase or entry inhibitors may be added if there is protease
      inhibitor intolerance or if an active NRTI backbone cannot be constructed
      CONCLUSION: Many options are available for second-line regimens. Decisions should
      be tailored to patients' needs and results of resistance testing. Two to three
      active agents must be included. Although the absolute number of agents is not
      critical, the goal is to develop a regimen that maximally suppresses HIV viral
      replication and provides an adequate barrier to prevent the emergence of
      resistance.

PMID- 20048717
TI  - Multidrug resistance: a clinical approach.
AB  - PURPOSE OF REVIEW: New antiretroviral agents have recently become available
      within existing and new drug classes, increasing treatment options for patients
      with multidrug-resistant virus. This review discusses the challenges that these
      new agents pose for the management of treatment-experienced patients. RECENT
      FINDINGS: Recent studies of the efficacy and safety of new antiretroviral drugs
      illustrate that drug regimens containing new agents are well tolerated and can
      suppress viremia in even the most drug-resistant patients. The goal of any new
      regimen should therefore be suppression of plasma HIV RNA levels to less than 50
      copies/ml, even in treatment-experienced patients. Patients should be given a
      regimen with at least two, or preferably three, fully active drugs after careful
      consideration of their treatment and adherence history, current and prior
      genotype tests, comorbidities, and concomitant medications. Newer and more
      tolerable agents also offer the possibility of regimen simplification among
      patients with multidrug-resistant HIV who are virologically suppressed. SUMMARY:
      Clinicians must optimize the pairing and sequencing of recently available
      antiretroviral agents. Future studies should continue to investigate the optimal
      use of new agents in order to further improve long-term treatment efficacy in
      patients with multidrug-resistant HIV infection.

PMID- 20048718
TI  - Drugs in traditional drug classes (nucleoside reverse transcriptase
      inhibitor/nonnucleoside reverse transcriptase inhibitor/protease inhibitors) with
      activity against drug-resistant virus (tipranavir, darunavir, etravirine).
AB  - PURPOSE OF REVIEW: This review focuses on the use of tipranavir/ritonavir,
      darunavir/ritonavir and etravirine for the treatment of HIV infection that has
      become resistant to protease inhibitors and/or nonnucleoside reverse
      transcriptase inhibitors. RECENT FINDINGS: Tipranavir/ritonavir and
      darunavir/ritonavir are boosted protease inhibitors highly active against HIV
      that has developed mutations that confer resistance to other protease inhibitors.
      For both drugs, there are scores to predict activity based on a combination of
      mutations. Best results are obtained when each drug is combined with one and
      preferably two other completely active antiretrovirals. The interaction profile
      and toxicity profile is better for darunavir/ritonavir, which in addition has
      shown positive outcomes in clinical trials of patients with early
      failure.Etravirine is a nonnucleoside reverse transcriptase inhibitor highly
      active against HIV that has developed mutations that confer resistance to
      nevirapine or efavirenz. Clinical trials results suggest that etravirine should
      be used with other active antiretrovirals. Best results for etravirine have been
      obtained in combination with darunavir/ritonavir in patients with extensive
      protease inhibitor and nonnucleoside reverse transcriptase inhibitor resistance.
      The role of etravirine for the treatment of early failure of efavirenz-based or
      nevirapine-based regimens remains to be elucidated. Resistance to etravirine
      requires the accumulation of multiple reverse transcriptase mutations different
      from K103N, which has no impact on activity. SUMMARY: Tipranavir/ritonavir,
      darunavir/ritonavir and etravirine are very important additions to the
      therapeutic armamentarium against HIV that has become resistant to protease
      inhibitors and nonnucleoside reverse transcriptase inhibitors.

PMID- 20048719
TI  - Novel drug classes: entry inhibitors [enfuvirtide, chemokine (C-C motif) receptor
      5 antagonists].
AB  - PURPOSE OF REVIEW: To provide an update on viral entry inhibitors focusing on
      recently published clinical trials, the routine clinical use of these
      medications, and future drug candidates. RECENT FINDINGS: Clinical trials and
      cohort studies support the efficacy of both enfuvirtide and maraviroc in the
      management of treatment-experienced patients. In clinical practice, tolerability
      issues, particularly injection site reactions, have limited the clinical use of
      enfuvirtide. Providers should be aware of the need for tropism determination and
      dosing requirements for maraviroc. The novel chemokine (C-C motif) receptor 5
      blocking agent, vicriviroc, has shown promise and is currently in phase III
      clinical development. SUMMARY: The rapid pace of scientific discovery and
      pharmaceutical development has led to the release of several novel and well
      tolerated antiretroviral agents, with activity against resistant isolates. Entry
      inhibitors remain a critical therapeutic option for treatment-experienced
      patients. Providers need to be familiar with these agents, and future drug
      development should be encouraged.

PMID- 20048720
TI  - Integrase inhibitors in salvage therapy regimens for HIV-1 infection.
AB  - PURPOSE OF REVIEW: To review current knowledge and the role of integrase
      inhibitors in the setting of HIV salvage therapy. We will discuss results from
      recent studies and literature and comment on the potential for integrase
      inhibitors in defined clinical settings. RECENT FINDINGS: Raltegravir has been
      studied most intensively in treatment-experienced patients and is the first
      integrase inhibitor that has been licensed for use in this patient group. Most
      studies have shown good tolerability data and very potent virus suppression. In
      patients with limited treatment options, switching from enfuvirtide appears to be
      well tolerated, whereas switching from a protease inhibitor-based regimen may
      increase the rates of viral failure. Elvitegravir also showed good results in
      early phase clinical trials and is currently undergoing phase III clinical
      trials. SUMMARY: Given that integrase inhibitors belong to a new class of
      antiretroviral agents with a diverse drug resistance profile, and are active
      against both chemokine (C-C motif) receptor 5 and chemokine (C-X-C motif)
      receptor 4 strains, they are exciting additions to salvage therapy regimen.
      Raltegravir and elvitegravir are metabolized via different pathways, which will
      affect their respective use. The major limitation for the use of integrase
      inhibitors is a potentially low threshold for viral drug resistance, so
      functional monotherapy must be avoided.

PMID- 20048721
TI  - Investigational agents for salvage.
AB  - PURPOSE OF REVIEW: There have been several new compounds developed from new and
      old antiretroviral drug classes recently that are active against highly resistant
      HIV-1. The management of patients who are highly drug experienced is complex and
      challenging and this article reviews current knowledge on the investigational
      agents in development for these patients. This review will examine some of the
      compounds that may have a role to play in highly experienced patients in the
      future. RECENT FINDINGS: Studies in early phases of therapy and some dose-ranging
      efficacy and safety clinical trials of investigational drugs have brought some
      drugs closer to licensing. New drugs in established classes not only have to be
      less toxic than the already licensed compounds but also have to be active against
      resistant viruses, these conditions make drug development difficult. SUMMARY: It
      is now possible for the majority of patients who are highly experienced in terms
      of drug treatment and who have virological failure to achieve HIV-1 viral loads
      below the limit of detection. There are, however, some patients who continue to
      have virological failure and develop further resistance and these patients need
      therapy that is effective; new drugs are being developed to meet this need.

PMID- 20048722
TI  - Resistance to novel drug classes.
AB  - PURPOSE OF REVIEW: Understanding the mechanisms that underlie resistance
      development to novel drugs is essential to a better clinical management of
      resistant viruses and to prevent further resistance development and spread.
      RECENT FINDINGS: Integrase inhibitors and CCR5 antagonists are the more recent
      antiretroviral classes developed. The HIV-1 integrase, responsible for the
      chromosomal integration of the newly synthesized double-stranded viral DNA into
      the host genomic DNA, represents a new and important target; and two integrase
      inhibitors (INIs), raltegravir and elvitegravir, have been shown promising
      results in clinical trials. Viral entry is also an attractive step for the
      development of new drugs against HIV variants resistant to current antiretroviral
      drugs, and two CCR5 antagonists have been designed to inhibit HIV-1 binding to R5
      co-receptor and are under clinical investigation. SUMMARY: Drug resistance to
      INIs occurs through the selection of mutations within HIV integrase. The kinetic
      of selection seems rapid and one mutation alone is able to confer resistance to
      integrase inhibitor, suggesting that this class of drug has a low genetic
      barrier. Two ways could explain the failure of the CCR5 antagonist class: a rapid
      outgrowth of pre-existing archived X4 virus or the selection of a resistance to
      CCR5 antagonists through amino acid changes in V3 loop.

PMID- 20048723
TI  - Management of antiretroviral failure and resistance in developing countries.
AB  - PURPOSE OF REVIEW: As scale-up of antiretroviral therapy in developing countries
      continues, an increasing number of patients developing antiretroviral failure and
      resistance are being identified. This review focuses on the identification and
      management of these complex patients in settings with limited antiretroviral drug
      options and resources. RECENT FINDINGS: The number of patients receiving second
      line and salvage therapies remains lower than the number of patients who are
      eligible for these therapies. This situation is a result of delays in the
      recognition and management of antiretroviral failure caused by a lack of
      sensitive diagnostic techniques, and effective and tolerable alternative
      antiretroviral drugs. Alternative treatment options using currently available
      therapies in developing countries are suggested for the management of patients
      with antiretroviral failure and resistance. Strategies to enhance the durability
      of antiretroviral regimens to minimize the risk of failure are also discussed.
      SUMMARY: The development of antiretroviral failure and drug resistance among HIV
      infected patients in developing countries is of increasing concern. Intensive
      efforts by HIV care and treatment programs are required to ensure the timely and
      effective diagnosis and management of these patients. Efforts to minimize the
      risk of failure are also needed given the significant cost and resource
      limitations in these settings.

PMID- 20048724
TI  - Decoding the Mediterranean diet. Basic ingredients at heart of healthy-eating
      plan.

PMID- 20048725
TI  - Occassional spikes in blood pressure could lead to more lasting problem.

PMID- 20048726
TI  - American Heart Association urges Americans to cut back on sugar.

PMID- 20048727
TI  - Pelvic problems. Muscle dysfunction can cause symptoms.

PMID- 20048728
TI  - Mayo Clinic office visit. Testing C-reactive protein. An interview with Thomas
      Behrenbeck, M.D., Ph.D.

PMID- 20048729
TI  - Healthy eating on a budget. Save on food without sacrificing nutrition.

PMID- 20048730
TI  - Are "e-cigarettes" safer than regular ones?

PMID- 20048731
TI  - What is ocular rosacea?

PMID- 20048736
TI  - Presynaptically silent synapses studied with light microscopy.
AB  - Synaptic plasticity likely underlies the nervous system's ability to learn and
      remember and may also represent an adaptability that prevents otherwise damaging
      insults from becoming neurotoxic. We have been studying a form of presynaptic
      plasticity that is interesting in part because it is expressed as a digital
      switching on and off of a presynaptic terminal s ability to release vesicles
      containing the neurotransmitter glutamate. Here we demonstrate a protocol for
      visualizing the activity status of presynaptic terminals in dissociated cell
      cultures prepared from the rodent hippocampus. The method relies on detecting
      active synapses using staining with a fixable form of the styryl dye FM1-43,
      commonly used to label synaptic vesicles. This staining profile is compared with
      immunostaining of the same terminals with an antibody directed against the
      vesicular glutamate transporter 1 (vGluT-1), a stain designed to label all
      glutamate synapses regardless of activation status. We find that depolarizing
      stimuli induce presynaptic silencing. The population of synapses that is silent
      under baseline conditions can be activated by prolonged electrical silencing or
      by activation of cAMP signaling pathways.

PMID- 20048740
TI  - Little vector, big gene transduction: fragmented genome reassembly of adeno
      associated virus.

PMID- 20048741
TI  - Stem cell vaccination against cancer: fighting fire with fire?

PMID- 20048744
TI  - New year, new improvements.

PMID- 20048743
TI  - Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human
      glioblastoma cells independent of PTEN status.
AB  - MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate
      gene expression after transcription. Aberrant expression of miRNAs has been shown
      to be involved in tumorigenesis. We showed that miR-21 was one of the most
      frequently overexpressed miRNA in human glioblastoma (GBM) cell lines. To explore
      whether miR-21 can serve as a therapeutic target for glioblastoma, we
      downregulated miR-21 with a specific antisense oligonucleotide and found that
      apoptosis was induced and cell-cycle progression was inhibited in vitro in U251
      (PTEN mutant) and LN229 (PTEN wild-type) GBM cells; xenograft tumors from
      antisense-treated U251 cells were suppressed in vivo. Antisense-miR-21-treated
      cells showed a decreased expression of EGFR, activated Akt, cyclin D, and Bcl-2.
      Although miR-21 is known to regulate PTEN and downregulation of miR-21 led to
      increased PTEN expression both endogenously and in a reporter gene assay, the GBM
      suppressor effect of antisense-miR-21 is most likely independent of PTEN
      regulation because U251 has mutant PTEN. Microarray analysis showed that the
      knockdown of miR-21 significantly altered expression of 169 genes involved in
      nine cell-cycle and signaling pathways. Taken together, our studies provide
      evidence that miR-21 may serve as a novel therapeutic target for malignant
      gliomas independent of PTEN status.

PMID- 20048746
TI  - Effect of prototypical inducers on ligand activated nuclear receptor regulated
      drug disposition genes in rodent hepatic and intestinal cells.
AB  - AIM: The aim of this study was to investigate the impact on expression of mRNA
      and protein by paradigm inducers/activators of nuclear receptors and their target
      genes in rat hepatic and intestinal cells. Furthermore, assess marked inter
      laboratory conflicting reports regarding species and tissue differences in
      expression to gain further insight and rationalise previously observed species
      differences between rodent and human based systems. METHODS: Quantitative real
      time-polymerase chain reaction (QRT-PCR) and immunoblots were used to assess
      messenger RNA (mRNA) and protein expression for CYP2B2, CYP3A1, CYP3A2, CYP3A9,
      ABCB1a, ABCB1b, ABCC1, ABCC2, pregnane X receptor (PXR), farnesoid X receptor
      (FXR) and constituitive androstane receptor (CAR) in rat hepatoma cell line
      H411E, intestinal cells, Iec-6, and rat primary hepatocytes, in response to
      exposure for 18 h with prototypical inducers. RESULTS: Dexamethasone (DEX) and
      pregnenolone 16alpha carbonitrile (PCN) significantly induced PXR, CYP3A9, ABCB1a
      and ABCB1b. However, when co-incubated, DEX appeared to restrict PCN-dependent
      induction. Chenodeoxycholic acid (CDCA) was the only ligand to induce FXR in all
      three cell types. Despite previously reported species differences between PCN and
      rifampicin (RIF), both compounds exhibited a similar profile of induction.
      CONCLUSION: Data presented herein may explain some of the discrepancies
      previously reported with respect to species differences from different
      laboratories and have important implications for study design.

PMID- 20048747
TI  - 4'-Chloro-3,5-dihydroxystilbene, a resveratrol derivative, induces lung cancer
      cell death.
AB  - AIM: To examine the antitumor effect of 4'-chloro-3,5-dihydroxystilbene, a
      resveratrol derivative, on lung adenocarcinoma A549 cells. METHODS: The cytotoxic
      IC(50) was determined by direct cell counting. Flow cytometry,
      monodansylcadaverine (MDC) staining, transfection, Western blot and a proteasome
      activity assay were used to study the cellular mechanism of 4'-chloro-3,5
      dihydroxystilbene. A xenograft nude mouse model was used to analyze the antitumor
      effect in vivo. RESULTS: 4'-Chloro-3,5-dihydroxystilbene induced a rapid and
      persistent increase in the intracellular reactive oxygen species in the cells,
      but the cell death could not be inhibited by two antioxidant agents. The
      derivative caused sub-G(1) formation, a decrease in the mitochondria membrane
      potential and poly (ADP-ribose) polymerase degradation, and the caspase inhibitor
      Z-VAD-FMK could partially prevent cell death. It also induced a significant
      increase in intracellular acidic vacuoles, LC3-II formation and intracellular GFP
      LC3 aggregation. An autophagic inhibitor partially reversed cell death.
      Additionally, 4'-chloro-3,5-dihydroxystilbene induced the accumulation of
      ubiquitinated conjugates and inhibited proteasome activity in cells. In an in
      vivo study, 4'-chloro-3,5-dihydroxystilbene retarded tumor growth in nude mice.
      CONCLUSION: These data suggest that the resveratrol derivative 4'-chloro-3,5
      dihydroxystilbene could be developed as an anti-tumor compound.

PMID- 20048748
TI  - Trichostatin A sensitizes cisplatin-resistant A549 cells to apoptosis by up
      regulating death-associated protein kinase.
AB  - AIM: To investigate the apoptosis-inducing effect of trichostatin A (TSA) in the
      human lung adenocarcinoma cisplatin-resistant cell line (A549/CDDP) and to
      examine whether TSA can enhance sensitivity to cisplatin treatment and the
      underlying molecular mechanisms of such an enhancement. METHODS: Cell viability
      was evaluated using the Neutral Red assay. Apoptosis was assessed using Hoechst
      33258 staining and flow cytometry analysis. Protein expression was detected by
      Western blotting. To determine the role of Death-associated protein kinase (DAPK)
      in TSA-induced apoptosis in the A549/CDDP cell line, cells were transfected with
      pcDNA3.1(+)-DAPK, which has a higher expression level of DAPK compared to
      endogenous expression, and DAPK activity was inhibited by both over-expression C
      terminal fragment of DAPK which may competitive binding DAPK substrates to
      inhibit the function of DAPK and RNA interference. RESULTS: TSA induced apoptosis
      in both A549 cells and A549/CDDP cells. TSA enhanced the sensitivity of A549/CDDP
      cells to cisplatin, along with concomitant DAPK up-regulation. When DAPK was over
      expressed, A549/CDDP cells became sensitive to cisplatin and the cytotoxicity of
      TSA could be increased. Moreover, the cytotoxicity of TSA could be alleviated by
      inhibition of DAPK activity by the expression of a recombinant C-terminal
      fragment of DAPK or RNA interference. CONCLUSION: TSA induced sensitivity to
      cisplatin treatment in cisplatin-resistant A549 cells. The up-regulation of DAPK
      is one of the mechanisms mediating sensitization to TSA-induced apoptosis in
      cisplatin-resistant cells.

PMID- 20048750
TI  - Advances in molecular genetics of panic disorder.
AB  - The molecular genetic research on panic disorder (PD) has grown tremendously in
      the past decade. Although the data from twin and family studies suggest an
      involvement of genetic factors in the familial transmission of PD with the
      heritability estimate near 40%, the genetic substrate underlying panicogenesis is
      not yet understood. The linkage studies so far have suggested that chromosomal
      regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 are associated with the
      transmission of PD phenotypes. To date, more than 350 candidate genes have been
      examined in association studies of PD, but most of these results remain
      inconsistent, negative, or not clearly replicated. Only Val158Met polymorphism of
      the catechol-O-methyltransferase gene has been implicated in susceptibility to PD
      by several studies in independent samples and confirmed in a recent meta
      analysis. However, the specific role of this genetic variation in PD requires
      additional analysis considering its gender- and ethnicity-dependent effect and
      putative impact on cognitive functions. The recent advantages in bioinformatics
      and genotyping technologies, including genome-wide association and gene
      expression methods, provide the means for far more comprehensive discovery in PD.
      The progress in clinical and neurobiological concepts of PD may further guide
      genetic research through the current controversies to more definitive findings.

PMID- 20048749
TI  - Expanding the range of ZNF804A variants conferring risk of psychosis.
AB  - A trio of genome-wide association studies recently reported sequence variants at
      three loci to be significantly associated with schizophrenia. No sequence
      polymorphism had been unequivocally (P<5 * 10(-8)) associated with schizophrenia
      earlier. However, one variant, rs1344706[T], had come very close. This
      polymorphism, located in an intron of ZNF804A, was reported to associate with
      schizophrenia with a P-value of 1.6 * 10(-7), and with psychosis (schizophrenia
      plus bipolar disorder) with a P-value of 1.0 * 10(-8). In this study, using 5164
      schizophrenia cases and 20,709 controls, we replicated the association with
      schizophrenia (odds ratio OR = 1.08, P = 0.0029) and, by adding bipolar disorder
      patients, we also confirmed the association with psychosis (added N = 609, OR =
      1.09, P = 0.00065). Furthermore, as it has been proposed that variants such as
      rs1344706[T]-common and with low relative risk-may also serve to identify regions
      harboring less common, higher-risk susceptibility alleles, we searched ZNF804A
      for large copy number variants (CNVs) in 4235 psychosis patients, 1173 patients
      with other psychiatric disorders and 39,481 controls. We identified two CNVs
      including at least part of ZNF804A in psychosis patients and no ZNF804A CNVs in
      controls (P = 0.013 for association with psychosis). In addition, we found a
      ZNF804A CNV in an anxiety patient (P = 0.0016 for association with the larger set
      of psychiatric disorders).

PMID- 20048752
TI  - Outcome parameters in spinal cord injury research: a systematic review using the
      International Classification of Functioning, Disability and Health (ICF) as a
      reference.
AB  - OBJECTIVES: This study is part of the development of an International
      Classification of Functioning, Disability and Health (ICF) Core Set for spinal
      cord injury (SCI). Its specific objectives were to identify outcome parameters
      reported in published studies on individuals with SCI in the early post-acute and
      chronic situation, and to identify and quantify the concepts of the reported
      parameters using the ICF as a reference. METHODS: Electronic searches of Medline,
      EMBASE, PsycINFO and CINAHL from 2001 to 2005 were carried out. All outcome
      parameters and their underlying concepts were retrieved from the included
      studies. These concepts were linked to categories of the ICF using standardized
      rules. RESULTS: From the 6681 abstracts retrieved, 2205 were randomly selected
      (33.0%) and 281 studies met the inclusion criteria (12.7%). A total number of
      5217 concepts were retrieved from standardized and non-standardized measures, of
      which 4049 (77.6%) could be linked to 175 different ICF categories: 56 out of 114
      Body Functions, 19 out of 56 Body Structures, 62 out of 118 Activities and
      Participation and 38 out of 74 Environmental Factors categories. Second-level
      categories reported in >20% of all studies were pain, remunerative employment,
      health services, systems and policies, school education and higher education.
      CONCLUSION: The ICF provides a valuable reference to identify and quantify the
      concepts of measures focusing on SCI in the early post-acute and chronic
      situation. The findings show a great diversity in the consequences of SCI and
      underscore the importance of social participation and environment for people with
      SCI.

PMID- 20048754
TI  - Diagnostic criteria of traumatic central cord syndrome. Part 1: a systematic
      review of clinical descriptors and scores.
AB  - STUDY DESIGN: Systematic review. BACKGROUND: The applied definition of traumatic
      central cord syndrome (TCCS) lacks specific quantified diagnostic criteria.
      OBJECTIVE: To review currently applied TCCS diagnostic criteria and quantitative
      data regarding the 'disproportionate weakness' between the upper and lower
      extremities described in original studies reporting on TCCS subjects. METHODS: A
      MEDLINE (1966 to 2008) literature search was conducted. The descriptors applied
      to define TCCS were extracted from all included articles. We included original
      studies that reported on the differences in motor score (based on the Medical
      Research Council scale) between the total upper extremity motor score (UEMS) and
      the total lower extremity motor score (LEMS), in a minimum of five TCCS patients
      at the time of hospital admission. The mean difference between the total UEMS and
      the total LEMS of the patients included in each study was calculated. Case
      reports were excluded. RESULTS: None of the identified studies on TCCS patients
      reported inclusion and/or exclusion criteria using a quantified difference
      between the UEMS and LEMS. Out of 30 retrieved studies, we identified seven
      different clinical descriptors that have been applied as TCCS diagnostic
      criteria. Nine studies reporting on a total of 312 TCCS patients were eligible
      for analysis. The mean total UEMS was 10.5 motor points lower than the mean total
      LEMS. CONCLUSIONS: There is no consensus on the diagnostic criteria for TCCS.
      Nevertheless, this review revealed an average of 10 motor points between the UEMS
      and LEMS as a possible TCCS diagnostic criterion. However, further discussion by
      an expert panel will be required to establish definitive diagnostic criteria.

PMID- 20048753
TI  - A systematic review of the therapeutic interventions for heterotopic ossification
      after spinal cord injury.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To conduct a systematic review of the
      effectiveness of interventions used to prevent and treat heterotopic ossification
      (HO) after spinal cord injury (SCI). SETTING: St Joseph's Parkwood Hospital,
      London, Ontario, Canada. METHODS: MEDLINE, CINAHL, EMBASE and PsycINFO databases
      were searched for articles addressing the treatment of HO after SCI. Studies were
      selected by two reviewers and were only included for analysis if at least 50% of
      the subjects had an SCI, there were at least three SCI subjects and if the study
      subjects participated in a treatment or intervention. Study quality was assessed
      by two independent reviewers using the Downs and Black evaluation tool for all
      studies, as well as the PEDro assessment scale for randomized control trials
      only. Levels of evidence were assigned using a modified Sackett scale. RESULTS: A
      total of 13 studies met the inclusion criteria. The selected articles were
      divided into prevention or treatment of post-SCI HO. Nonsteroidal anti
      inflammatory drugs (NSAIDs), warfarin, and pulse low-intensity electrogmagnetic
      field (PLIMF) therapy were reviewed as prophylactic measures. Bisphosphonates,
      radiotherapy and excision were reviewed as treatments of post-SCI HO.
      CONCLUSIONS: Pharmacological treatments of HO after SCI had the highest level of
      research evidence supporting their use. Of these, NSAIDs showed greatest efficacy
      in the prevention of HO when administered early after an SCI, whereas
      bisphosphonates were the intervention with strongest supportive evidence once HO
      had developed. Of the non-pharmacological interventions, PLIMF was supported by
      the highest level of evidence; however, more research is needed to fully
      understand its role.

PMID- 20048755
TI  - Parameters for positive outcome of the in-hospital rehabilitation of spinal cord
      lesion patients: the Boberg Quality Score.
AB  - STUDY DESIGN: Monocentric Cohort Study. OBJECTIVE: Development of a multi
      dimensional outcome score of the rehabilitation of spinal cord injury (SCI)
      patients. SETTING: Level 1 Trauma centre with large spinal unit. METHODS: During
      the rehabilitation of 161 patients with SCI between 2005 and 2007 following
      outcome parameters were assessed at different time points: functional status,
      pain, emotion, energy, sleep, social isolation, knowledge and self-management
      attitude. The results for these parameters were statistically evaluated with
      regard to different grades of paralysis and analyzed for socio-demographic
      influence factors. Correlation and factor analysis were then applied to evaluate
      the dependencies of the parameters and the dimensional structure of the applied
      score. RESULTS: For all factors a positive trend was found during the course of
      rehabilitation. Only the functional status is caused by spinal cord lesion. Age,
      sex and social isolation have no direct influence on the result with regard to
      functional status. For interactive dependencies of the parameters a three
      dimensional structure was found: Success in the parameters, emotion, energy or
      social status, is independent of success in the parameter functional status. The
      result of the functional status is, next to the type of spinal injury, mainly
      influenced by the self-management attitude. The level of knowledge gained during
      rehabilitation is independent of the success in the other parameters. CONCLUSION:
      By the combination of functional, psychological and cognitive parameters into a
      result score it is possible to determine the quality of a rehabilitation process
      in its multiple dimensions and for different levels and grades of palsy. By this
      it is possible to analyze and compare the effectiveness and efficiency of
      rehabilitation on a national and international level. Longitudinal comparison of
      the long-term effects of rehabilitation after SCI is also possible, for example,
      in the course of follow-up examinations. SPONSORSHIP: Deutsche Gesetzliche
      Unfallversicherung (German Statutory Occupational Accident Insurance).

PMID- 20048751
TI  - Differential effects of prenatal and postnatal expressions of mutant human DISC1
      on neurobehavioral phenotypes in transgenic mice: evidence for neurodevelopmental
      origin of major psychiatric disorders.
AB  - Strong genetic evidence implicates mutations and polymorphisms in the gene
      Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and
      mood disorders. Recent studies have shown that DISC1 has important functions in
      both brain development and adult brain function. We have described earlier a
      transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1)
      that acts in a dominant-negative manner to induce the marked neurobehavioral
      abnormalities. To gain insight into the roles of DISC1 at various stages of
      neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1)
      only prenatal period, (2) only postnatal period, or (3) both periods. All periods
      of expression similarly led to decreased levels of cortical dopamine (DA) and
      fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal
      expression produced increased aggression and enhanced response to
      psychostimulants in male mice along with increased linear density of dendritic
      spines on neurons of the dentate gyrus of the hippocampus, and lower levels of
      endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain
      volume, whereas selective postnatal expression gave rise to decreased social
      behavior in male mice and depression-like responses in female mice as well as
      enlarged lateral ventricles and decreased DA content in the hippocampus of female
      mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1
      exerts differential effects on neurobehavioral phenotypes, depending on the stage
      of development at which the protein is expressed. The multiple and diverse
      abnormalities detected in mutant DISC1 mice are reminiscent of findings in major
      mental diseases.

PMID- 20048756
TI  - Glucose tolerance and physical activity level in people with spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional, observational study. OBJECTIVES: To evaluate the
      associations of physical activity and neurological lesion level with glucose
      tolerance in people with spinal cord injury (SCI). SETTING: New South Wales,
      Australia. METHODS: Twenty-five people (5 women, 20 men) with SCI (>6 months post
      injury) aged between 18 and 65 years were recruited. Exclusion criteria included
      known coronary heart disease, stroke or diabetes. Participants underwent an oral
      glucose tolerance test. Fasting and 2-h plasma glucose concentrations were
      classified according to the World Health Organization categories of glycemia.
      Participants also completed the Physical Activity Scale for Individuals with
      Physical Disabilities and mean MET-hours day(-1) was calculated. Associations
      with the 2-h plasma glucose concentration were calculated through multiple and
      stepwise regressions. RESULTS: Participants presented with complete or incomplete
      tetraplegia (n=11 TETRA) or complete or incomplete paraplegia (n=14 PARA) with
      neurological lesion levels ranging from C3/4 to T12. Mean 2-h plasma glucose was
      7.13+/-2.32 mmol l(-1). Nine participants had disordered glycemia (n=6 TETRA; n=3
      PARA) and the remaining participants had normal glucose tolerance. Those
      participants with normal glucose tolerance participated in more moderate-vigorous
      and strength exercise and undertook more non-exercise-related mobility than those
      with disordered glycemia. Physical activity and age, but not lesion level were
      independent determinants of 2-h plasma glucose concentration (r=0.683, P=0.001),
      explaining 47% of the variance. CONCLUSION: Physical activity level is
      independently associated with glucose tolerance in people with SCI. Non-exercise
      activity may also be important for maintaining normal glycemia.

PMID- 20048757
TI  - Neuroanatomy and neurophysiology related to sexual dysfunction in male neurogenic
      patients with lesions to the spinal cord or peripheral nerves.
AB  - STUDY DESIGN: Review article. OBJECTIVES: The neuroanatomy and physiology of
      psychogenic erection, cholinergic versus adrenergic innervation of emission and
      the predictability of outcome of vibration and electroejaculation require a
      review and synthesis. SETTING: University Hospital Belgium. METHODS: We reviewed
      the literature with PubMed 1973-2008. RESULTS: Erection, emission and ejaculation
      are separate phenomena and have different innervations. It is important to
      realize, which are the afferents and efferents and where the motor neuron of the
      end organ is located. When interpreting a specific lesion it is important to
      understand if postsynaptic fibres are intact or not. Afferents of erection,
      emission and ejaculation are the pudendal nerve and descending pathways from the
      brain. Erection is cholinergic and NO-mediated. Emission starts cholinergically
      (as a secretion) and ends sympathetically (as a contraction). Ejaculation is
      mainly adrenergic and somatic. For vibratory-evoked ejaculation, the reflex arch
      must be complete; for electroejaculation, the postsynaptic neurons (paravertebral
      ganglia) must be intact. CONCLUSION: Afferents of erection, emission and
      ejaculation are the pudendal nerve and descending pathways from the brain.
      Erection is cholinergic and NO-mediated. Emission starts cholinergically (as a
      secretion) and ends sympathetically (as a contraction). Ejaculation is mainly
      adrenergic and somatic. In neurogenic disease, a good knowledge of neuroanatomy
      and physiology makes understanding of sexual dysfunction possible and
      predictable. The minimal requirement for the success of penile vibration is a
      preserved reflex arch and the minimal requirement for the success of
      electroejaculation is the existence of intact post-ganglionic fibres.

PMID- 20048758
TI  - Transrectal high-intensity focused ultrasound (HIFU) treatment of localized
      prostate cancer: review of technical incidents and morbidity after 5 years of
      use.
AB  - The objective of this study was to report on technical incidents and early and
      late complications occurring in high-intensity focused ultrasound (HIFU)
      treatment of patients with localized prostate cancer. We performed a
      retrospective review of patients who were treated by Ablatherm at our centre. We
      recorded all technical incidents, treatment discontinuations and early (<1 month)
      and late complications. A total of 74 HIFU procedures were performed in 65
      patients (55 first-line HIFU treatments and 10 cases of salvage therapy after
      radiotherapy) over a 5-year period. Median follow-up was 41 months (10-64
      months). All the procedures were well tolerated and no intra- or peri-operative
      deaths occurred. Six technical incidents in the overall population (8.1%) led to
      discontinuation of the procedure. The early complication rate in patients
      undergoing first-line HIFU was 36.4%: urinary retention (20%), dysuria (5.4%),
      urinary infection (3.6%), haematuria (3.6%) and urethral stenosis (3.6%). The
      late complication rate was 12.7%: urethral stenosis (9%) and dysuria (3.6%).
      There were no cases of rectourethral fistula. The long-term urinary incontinence
      rate was 20% and the de novo erectile dysfunction rate was 77.1%. Nine
      complications (16.4%) required surgical management. The overall complication rate
      was 49%. Ablatherm is a reliable technique with a relatively high complication
      rate. However, most complications were minor and required surgical management in
      a few cases only. Our results confirm that all patients who are offered HIFU
      treatment should be properly informed of the risks, in particular with regard to
      continence and sexual function.

PMID- 20048759
TI  - Immunolocalization of STIM1 in the mouse brain.
AB  - Capacitative Calcium Entry (CCE) in neurons seems to depend, as in non-excitatory
      cells, on endoplasmic reticulum calcium sensors STIM1 or STIM2. We show
      localization of STIM1 in the mouse brain by immunohistochemistry with a specific
      antibody. STIM1 immunoreactivity has wide, but not uniform, distribution
      throughout the brain and is observed in neuropil and cells. The most intensive
      immunoreactivity is observed in Purkinje neurons of cerebellum. High/moderate
      levels of immunostaining are found in hippocampus, cerebral cortex and in cortico
      medial amygdala, low in thalamus and basolateral amygdala. Co-staining with anti
      NeuN antibody identify STIM1 immunopositive cells as neurons. Real time PCR
      demonstrates that Stim2 expression is 7-fold higher than that of Stim1 in
      hippocampus and 3-fold in other regions. Immunoblotting confirms that levels of
      STIMs vary in different brain regions. The data show that STIM1 and STIM2 are
      present in the brain, thus both can be involved in CCE, depending on neuronal
      type.

PMID- 20048760
TI  - Xenon blocks AMPA and NMDA receptor channels by different mechanisms.
AB  - The noble gas xenon (Xe) inhibits not only NMDA receptors (NMDARs) but also the
      two other subtypes of glutamate receptor i.e. AMPA (AMPARs) and kainate
      receptors. Preliminary studies on AMPARs suggest that Xe sensitivity might be
      coupled to receptor desensitization. In order to find out if this hypothesis can
      be applied to all glutamate receptors, we analyzed additional 'non-desensitizing'
      AMPARs mutants and compared these with homologous mutants of NMDARs. Membrane
      currents of Neuro2A or SH-SY5Y cells transfected with cDNA encoding AMPA- or NMDA
      receptors were investigated by whole cell recordings under voltage clamp
      conditions. Agonists (glutamate, kainate, NMDA) were applied to the cells by
      means of a rapid perfusion system. Xenon was preincubated for 20 s before testing
      it in combination with the particular agonist. Xe (3.5 mM) reduced peak and
      plateau currents of AMPA wild-type receptors [GluR1(i); GluR2(i,Q)] activated for
      5 s with 3 mM glutamate, by 45 and 55% respectively. With mutant AMPARs showing
      greatly diminished or abolished desensitization i.e. GluR1(i)_L497Y,
      GluR1(i)_A636T(Lc) GluR2(i,Q)_R649E and GluR2(i,Q)_A643T(Lc) the reduction by Xe
      was significantly smaller and varied by between 4 and 20%. In contrast, no
      difference in the blocking capacity of Xe was observed comparing wild-type NR1
      1a/NR2A receptors with receptors having point mutations within NR2A that
      substantially slowed (NR2A_A651T(Lc)) or accelerated (NR2A_M823W) receptor
      desensitization. Thus, our data indicate that in AMPARs channel blockade by Xe is
      related to desensitization, whereas in NMDARs no evidence for such a relation was
      found. Thus, Xe seems to exert its inhibiting effect on various ionotropic
      glutamate receptors by different molecular mechanisms.

PMID- 20048761
TI  - Expression of bone morphogenetic proteins-2/4 in neural stem cells and their
      lineages.
AB  - Neural stem cells (NSCs) are multipotent progenitor cells that possess the
      ability to self-renew and generate different neural cell types. Bone
      morphogenetic proteins (BMPs) play critical roles in the determination of the
      fate of NSCs. Although some reports delineate BMP expression in the early
      developing central nervous system (CNS) they deal mainly with its expressions in
      restricted areas. However, little information is available for BMP expression in
      NSCs and their lineages. In this study, based on an in vitro model in which NSCs
      can self-renew and differentiate into astrocytes, neurons or oligodendrocytes, we
      mimicked the environment of NSC development in vivo. Using an antibody which can
      recognize BMP-2 and BMP-4, we showed that BMP-2/4 is only expressed in
      astrocytes. Inflammatory cytokines (tumor necrosis factor-alpha and/or interferon
      gamma) do not influence the expression pattern of BMPs in NSCs and their
      lineages. These results suggest that astrocytes might be one source of BMPs
      during the differentiation of NSCs and in the inflammatory environment after CNS
      injury.

PMID- 20048762
TI  - Changes in NGF/c-Fos double staining in the structures of the limbic system in
      juvenile and aged rats exposed to forced swim test.
AB  - This study aimed to investigate the influence of acute (a single 15 min) and
      chronic (15 min daily for 21 days) exposure to forced swim (FS) test on nerve
      growth factor (NGF)/c-Fos cells in hypothalamic paraventricular (PV) and
      supraoptic (SO) nuclei, the central (CeA) and medial (MeA) amygdaloid nuclei and
      CA3-hippocampus in juvenile (P28) and aged (P360) rats. The double
      immunofluorescence (-ir) method was used to detect NGF-ir and c-Fos-ir cells. The
      amount of NGF/c-Fosir cells in relation to all NGF-ir cells is shown as a
      percentage. In the acute FS test an increase in NGF/c-Fos-ir cells (P<.05) was
      observed in all studied structures of juvenile rats and in the PV and SO of the
      aged individuals. After chronic FS stress, the NGF/c-Fos-ir ratio remained
      unaltered (except in the SO) in P28, but it increased (P<.05) in all investigated
      regions in P360 compared with the controls. The findings may reflect the state of
      molecular plasticity within the limbic hypothalamicpituitary- adrenocortical
      (HPA) axis in both age groups, yet the phenomenon of habituation in NGF/c-Fos-ir
      after chronic FS exposure was observed only in juvenile animals.

PMID- 20048763
TI  - Alcohol reverses depressive and pronociceptive effects of chronic stress in mice
      with enhanced activity of the opioid system.
AB  - The role of the opioid system in mediating effects of alcoholism and stress in
      depression is far from clear. We studied, therefore, the effects of chronic mild
      stress (CMS) and alcohol drinking on depression-like behavior and nociception in
      lines of mice selected for high (HA) or low (LA) swim stress-induced analgesia.
      Compared to the LA mice, the HA animals display up-regulation of opioid receptor
      system function and depression-like behavior in tail suspension test (TST). We
      report now that alcohol reverses depressive and pronociceptive effect of CMS in
      HA mice. In contrast, in LA mice CMS does not affect nociception or behavior in
      TST and the animals are not susceptible to alcohol under CMS. The results suggest
      that opioid system activity may determine the effects of alcohol on behavior
      under stress and, therefore, link predispositions to depression and to
      alcoholism.

PMID- 20048764
TI  - GABA receptor subunits in human auditory cortex in normal and stroke cases.
AB  - GABA receptors are ubiquitous in the cerebral cortex and play a major role in
      shaping responses of cortical neurons. GABA(A) and GABA(B) receptor subunit
      expression was visualized by immunohistochemistry in human auditory areas from
      both hemispheres in 9 normal subjects (aged 43-85 years; time between death and
      fixation 6-24 hours) and in 4 stroke patients (aged 59-87 years; time between
      death and fixation 7-24 hours) and analyzed qualitatively for GABA(A) and
      semiquantitatively for GABA(B) receptor subunits. In normal brains, the primary
      auditory area (TC) and the surrounding areas TB and TA displayed distinct GABA(A)
      receptor subunit labeling with differences among cortical layers and areas. In
      postacute and chronic stroke we found a layer-selective downregulation of the
      alpha-2 subunit in the anatomically intact cerebral cortex of the intact and of
      the lesioned hemisphere, whereas the alpha-1, alpha-3 and beta-2/3 subunits
      maintained normal levels of expression. The GABA(B) receptors had a distinct
      laminar pattern in auditory areas and minor differences among areas. Unlike in
      other pathologies, there is no modulation of the GABA(B) receptor expression in
      subacute or chronic stroke.

PMID- 20048765
TI  - Thalidomide fails to be therapeutic following contusive spinal cord injury in
      rats.
AB  - Mechanical damage to the spinal cord (SC) generates self-destructive processes
      that contribute to post-traumatic neurodegeneration. Because thalidomide
      apparently counteracts these effects its use clinically has been proposed
      enthusiastically. Nonetheless, we tested its action as a neuroprotectant in a
      clinically relevant model of SC injury in rats. We administered thalidomide
      intraperitoneally to rats subjected to thoracic SC contusion as single or
      repeated doses within the first 24 h after injury. Edema, neutrophil
      infiltration, and cord tissue preservation/destruction were assessed in the SC 24
      h after injury and motor function for 7 weeks. Rats treated with thalidomide
      showed significant increase in SC water compared with naive rats, but not vehicle
      treated rats; their neutrophil infiltration and amount of spared/destroyed cord
      tissue was not different from vehicle-treated rats; and in no case was motor
      performance improved after thalidomide. In conclusion, thalidomide failed here to
      be therapeutic, discouraging its use clinically for SC trauma.

PMID- 20048766
TI  - Centroid extraction and illusions of extent with different contextual flanks.
AB  - In the present study, a computational model of the automatic centroid extraction
      based on the processes of local integration of excitatory profiles in the visual
      pathways has been developed. The model predictions have been compared with the
      results of our psychophysical examination of the perceptual distortions of the
      spatial extent. In experiments, the subjects matched two spatial intervals
      flanked by one of the three types of the contextual objects: either the Muller
      Lyer wings, or vertical stripes, or spot pairs. A good resemblance between the
      theoretical functions and dependencies of the illusions' magnitudes on various
      spatial parameters of the stimuli has provided evidence that the effects caused
      by indirect positional coding via centroids are powerful enough to explain the
      phenomena of the geometric illusions investigated.

PMID- 20048767
TI  - Cortical lateralization patterns related to self-estimation of emotional state.
AB  - The relationships between subjectively-reported emotional state and hemispheric
      laterality were investigated. Participants' emotional state was modified using
      emotional slides. Self-estimation of Energy Arousal and Hedonic Tone (positive
      valence) as well as Tense Arousal (negative valence) was derived from the
      Activation-Deactivation Adjective Checklist and the UWIST Mood Adjective
      Checklist. Energy arousal was found to be associated with right frontal dominance
      in the alpha2 (10-12 Hz) band, together with left frontal dominance in the beta2
      (16-24 Hz) band. It was also related to left alpha2 dominance in the central and
      centro-parietal cortex. The effects for the Hedonic Tone scale were limited to a
      frontal beta2 effect. Surprisingly, no effects of state estimates from the
      tension scales were observed. It can be concluded that selected qualities of
      subjective emotional state measured by adjective lists can be related in specific
      ways to hemispheric laterality, as measured by EEG methods.

PMID- 20048768
TI  - Behavioral sleep in captive owl monkey (Aotus azarae) and squirrel monkey
      (Saimiri boliviensis).
AB  - The objective of this study was to test the hypothesis that activity-behavioral
      sleep parameters differ between nocturnallyactive owl monkeys and diurnally
      active squirrel monkeys which are sympatric and of Bolivian origin. The total
      sleep time (TST) and sleep episode length (SEL) of 7 adult owl monkey siblings
      and 4 adult squirrel monkeys were quantitated by actigraphy for 7 days under
      captive conditions. The higher TST/24 h values and longer SEL/12 h quiescent
      phase quantitated for owl monkeys in comparison to that of squirrel monkeys
      clearly indicate that the behavioral sleep is markedly different between these
      two groups, though they are sympatric in wild. Significant differences noted in
      the sleep architecture between squirrel monkeys and owl monkeys can be attributed
      to the influences in the selected sleep niche, threat perception from predators,
      and disturbances from natural elements (especially rain) in the natural habitat.

PMID- 20048769
TI  - Is spatial memory transformed during the consolidation process? Effect of
      reminding.
AB  - Several studies in rats have shown activation of cortical regions and concurrent
      deactivation of the hippocampus during the retrieval of spatial memory, as the
      consolidation process progresses. To determine whether during this post-learning
      period of memory reorganization, spatial memories are transformed from a specific
      to a more generic representation, in Experiment 1 we compare remote spatial
      memory measured using a single probe trial versus relearning. Results show that
      spatial memory can be effectively retrieved using a single probe trial during the
      18 days following learning; after this time a retraining procedure is necessary.
      In Experiment 2 and 3 we tested the effect of a reminder treatment on the
      retrieval of remote memory. Results indicate that when the reminder was applied
      after experimental day 18, the treatment did not significantly improve the
      retrieval of spatial memory during a retention test (Exp. 2); however, if the
      reminder was applied before day 18, a significant improvement during the
      retention test was observed (Exp. 3). In order to investigate the extent to which
      memory becomes more difficult to retrieve as time passes due specifically to a
      retrieval deficit, in experiment 4 no significant differences, but marginal ones,
      were detected between an overtrained group and a control group when the retention
      test took place 30 days after the end of learning. Overall, the present results
      suggest that as the consolidation process progresses, spatial information becomes
      more difficult to recover, in part because the original detailed trace has
      gradually been transformed into a more schematic representation.

PMID- 20048770
TI  - ERPs and the evoked cardiac response to auditory stimuli: Intensity and cognitive
      load effects.
AB  - The evoked cardiac response (ECR) may be described as the sum of two independent
      response components: an initial HR deceleration (ECR1) and a slightly later
      acceleration (ECR2) hypothesized to reflect stimulus registration and cognitive
      processing load, respectively. This study investigated processing load effects in
      the ECR and the event-related potential (ERP). Stimulus intensity was varied
      within subjects, and cognitive load was varied between subjects, in a counting/no
      counting task with a long interstimulus interval. The ECR showed a significant
      effect of counting, but not intensity. ERPs showed the expected obligatory
      processing effects in the N1, and substantial effects of cognitive load in the
      Late Positive Complex. Both ERP components varied with intensity. These novel
      data offer support for ANS-CNS similarities in reflecting some aspects of
      stimulus processing, but further work is needed to understand the possible
      contribution of ERP subcomponents to these effects.

PMID- 20048771
TI  - Paradoxical form of filled/empty optical illusion.
AB  - The filled/empty illusion (Oppel-Kundt) is one of the oldest geometrical-optical
      illusions, but the determinants of the illusion are not yet sufficiently
      understood. We studied magnitude of the illusory effect as a function of the
      height of vertical strokes subdividing a spatial extension of fixed length, using
      the psychophysical standard-variable matching paradigm. For vertical strokes
      shorter than, or of the same height as strokes delimiting the standard, the
      length was over-reproduced consistently with earlier studies of the illusion.
      However, for vertical strokes three times longer than the delimiters, the
      illusory effect paradoxically decreased, and attained negative values in two of
      six subjects. The magnitude of the effect thus depends on the patterning of the
      space between the delimiters, not merely on the number of subdividing elements.

PMID- 20048772
TI  - Diverse functions of perineuronal nets.
AB  - Perineuronal nets represent well-organised components of the extracellular
      matrix, which are surrounding cell bodies, dendrites, and axon segments of a
      particular class of neurones as well as forming lattice-like structures. The role
      of perineuronal nets is not fully elucidated yet. Perineuronal nets may play a
      beneficial role by stabilizing the extracellular milieu assuring the
      characteristic features of enveloped neurons and protecting them from the
      influence of harmful agents. On the other hand, perineuronal nets create a
      barrier which limits neuronal plasticity and counteracts regeneration. This
      review examines recent evidence concerning the significance of the occurrence of
      perineuronal nets.

PMID- 20048774
TI  - The response of scanning Fabry-Perot interferometers to atomic transition
      profiles.

PMID- 20048773
TI  - Nonlinearity in holey optical fibers: measurement and future opportunities
      errata.

PMID- 20048775
TI  - Synchronization of several Q-switched optical masers.

PMID- 20048776
TI  - Vertical double-pass multiple reflection element for internal reflection
      spectroscopy.
AB  - A vertical double-pass internal reflection element for internal reflection
      spectroscopy is described which can be dipped into vessels containing liquids or
      powders to record their spectra. It has the advantage over the horizontal double
      pass internal reflection element in that no additional optical components are
      required to reorient the spectrometer slit image. Photographs are presented of
      internal reflection elements showing the actual paths of the light beams outside
      and inside the internal reflection elements.

PMID- 20048777
TI  - A laser output coupler using frustrated total internal reflection.
AB  - A unique component has been developed, constructed, and incorporated into an
      optically pumped ruby laser system. Without using thin film optical coatings,
      this component allows a known fraction of the radiation to be coupled from a
      laser system while simultaneously serving as the partial reflector at the output
      end of the laser. The output coupler, herein described, utilizes a frustrated
      total internal reflection configuration and is fabricated of fused silica with an
      air gap 0.483 micro in thickness as the critically controlled element. Techniques
      have been developed for establishing and maintaining the spacing of the silica
      members to a predetermined fraction of the ruby emission wavelength of 6943 A.
      The measured transmission, reflection, and scattering loss characteristics of the
      coupler are discussed. In addition, schematic diagrams and photographs of the
      operating coupler are shown. This coupler has withstood repeated Q-spoiled bursts
      of laser radiation without damage. However, equivalent radiation pulses have
      consistently destroyed dielectric reflectors. Thus, more reproducible laser
      experiments can be performed with this coupler than with conventional optically
      coated reflectors.

PMID- 20048778
TI  - The frustrated total reflection filter. 1. Spectral analysis.
AB  - The method of modal expansion is used to develop a theory for the analysis of
      frustrated total reflection (FTR) filters or similar layered systems of finite
      lateral extent. The theory is applied to determine the (spectral) transmission
      properties of the FTR filter of finite lateral extent (for an incident plane wave
      propagating in direction of maximum transmission). It is found that the
      finiteness of the lateral dimensions of the filter has a great effect on the
      transmission properties of the filter. The results are in agreement with
      available experimental data and clearly show that the unbounded wave theory
      (i.e., an analysis which assumes that both the incident electromagnetic radiation
      and the filter are of infinite lateral extent) cannot be applied to FTR filters
      even when the lateral filter dimensions are several orders of magnitude larger
      than the wavelength of the incident radiation.

PMID- 20048779
TI  - Improvement of silicon solar cell performance through the use of thin film
      coatings.
AB  - Thin film coatings are used universally in solar cell power systems for
      spacecraft. Antireflective coatings are used to increase the amount of useful
      energy reaching the active surface of the cell. Multilayer interference filters
      are employed to reject unwanted portions of the solar spectrum in order to reduce
      equilibrium temperature and to prevent ultraviolet damage. Glass covers are used
      in conjunction with these coatings for the purpose of increasing the thermal
      emittance of the surface. Appreciable performance increases can be obtained
      through the uses of these filters and coatings.

PMID- 20048780
TI  - Optics and spectroscopy.

PMID- 20048781
TI  - Evaporated inhomogeneous thin films.
AB  - A theoretical and experimental investigation of inhomogeneous CeO(2)-MgF(2) and
      ZnS-Na(3)AIF(6) anti-reflection coatings for the visible spectrai region has been
      made. By a proper choice of the refractive index profile, the reflectance may be
      considerably reduced. In the infrared region, Ge-MgF(2) films on Ge substrates
      are shown to give a low reflectance with a small wavelength dependence.

PMID- 20048782
TI  - Optical properties of multisource thermally evaporated III-V semiconductor
      compounds.
AB  - A variety of III-V semiconductor films has been prepared using the multisource
      technique. The availability of such layers widens the possibilities for applying
      semiconductors to optical components requiring controlled layers such as
      interference filters. A study of the dispersion of refractive indices in films of
      InSb and InAs indicates that such properties behave similarly to those of the
      bulk materials. However, those absorption processes which are determined by
      excess carrier scattering can become much larger than in the bulk. Intrinsic edge
      absorption in n-type InAs films exhibits exponential behavior similar to that of
      bulk samples having approximately the same carrier concentrations. Solid
      solutions of III-V mixtures can be effected using the multisource technique
      permitting studies of such parameters as effective masses and reststrahlen
      frequencies as functions of the solutions. The reststrahlen frequency for a
      Ga((3/4))In((1/4))Sb film is given.

PMID- 20048783
TI  - Computational method for determining n and k for a thin film from the measured
      reflectance, transmittance, and film thickness.
AB  - A computational method of determining n and k for an evaporated film from the
      measured reflectance, transmittance, and film thickness has been programmed for
      an IBM 7094 computer. The method consists of modifications to the NOTS multilayer
      film program. The basic program computes normal incidence reflectance,
      transmittance, phase change on reflection, and other parameters from the optical
      constants and thicknesses of all materials. In the modification, n and k for the
      film are varied in a prescribed manner, and the computer picks from among these
      values one n and one k which yield reflectance and transmittance values almost
      equalling the measured values. Results are given for films of silicon and
      aluminum.

PMID- 20048784
TI  - Further studies on MgF(2)-overcoated aluminum mirrors with highest reflectance in
      the vacuum ultraviolet.
AB  - MgF(2)-overcoated aluminum films with high-vacuum ultraviolet reflectance have
      been the subject of further investigations of the preparation parameters
      affecting their reflectance, and of the effect of aging and exposure to
      conditions likely to be encountered in their applications. Techniques for
      monitoring the thickness of MgF(2) by reflectance measurements with ultraviolet
      light and by complete evaporation of weighed quantities of MgF(2) are described.
      It is shown that MgF(2)-protected aluminum mirrors retain their high-vacuum
      ultraviolet reflectance during extended exposure to air, ultraviolet irradiation,
      and bombardment with 1-MeV electrons and 5-MeV protons, and that such mirrors can
      be easily cleaned if contaminated with oil.

PMID- 20048786
TI  - Stresses developed in optical film coatings.
AB  - The development of stress in evaporated dielectric and metal films, used as
      optical coatings, has been investigated experimentally by observing the bending
      of a thin silica strip as it becomes coated. The strip forms one mirror of a
      laser interferometer mounted within the coating chamber, giving high measurement
      sensitivity. Stress data on a number of materials commonly used in coating are
      presented, and the behavior of multilayer coatings investigated. Analysis of the
      effect of film stress upon the figure of optical surfaces is given, and the
      influence of stress upon the mechanical stability of multilayers is discussed.

PMID- 20048787
TI  - Realisations d'empilements de couches minces dielectriques d'epaisseurs
      quelconques; utilisation d'un calculateur analogique.
AB  - The preparation of dielectric multilayer coatings of nonequal thicknesses poses a
      problem of close control. The procedures of optical control of the coating itself
      (measurement of R or T extremes of R or T zeros of dR/dlambda, usually reserved
      for lambda/4 stacks) may also be used here; a preliminary study with the aid of
      an analog computer allows one to foresee progressively the different stages and
      to choose for each of the layers, the most precise method. The experimental
      results agree with the predicted.

PMID- 20048788
TI  - Multilayer mirrors with high reflectance over an extended spectral region.
AB  - The design of mirrors composed of multilayer stacks of dielectric films is
      considered. High reflectance over an extended spectral range is attained by
      positioning the stacks so that on a wavelength scale their high-reflectance bands
      are either contiguous or overlapping. Certain precautions must be taken in the
      choice of stacks to avoid deep-reflectance minima from developing within the
      extended high-reflectance region. Some of these are discussed and illustrated
      with both computional and experimental curves. The techniques of extending the
      high-reflectance regions are applicable not only to mirrors, but also to low- and
      high-pass cutoff filters and to multilayer polarizers.

PMID- 20048789
TI  - On a dielectric multilayer fiber by baumeister.
AB  - It is well known that the reflection in the passband of dielectric multilayer
      filters can be appreciably reduced by small adjustments in the layer thicknesses.
      Baumeister designed such a filter using a computer program to refine an initial
      approximate design. This paper presents another design approach based on the
      concept of Herpin equivalent layer.

PMID- 20048790
TI  - High performance blocking filters for the region 1 micro to 20 micro.
AB  - A set of filters based on the sequence of semiconductor edges is described which
      offers continuity of short-wave infrared blocking. The rejection throughout the
      stop region is greater than 10(3) for each filter and the transmission better
      than 70% through one octave with a square cutoff. The cutoff points are located
      at intervals of about two-thirds of an octave. Filters at 2.6 micro, 5.5 micro,
      and 12 micro which use a low-passing multilayer in combination with a
      semiconductor absorption edge are described in detail. The design of multilayers
      for optimum performance is discussed by analogy with the synthesis of electric
      circuit filters.

PMID- 20048791
TI  - Infrared modulation by means of frustrated total internal reflection.
AB  - Most infrared systems and instruments require mechanical chopping or scanning
      mechanisms for modulating the radiation signal. For some applications,
      particularly in space, it is desirable to eliminate sliding or rotating
      mechanical components. One means of accomplishing this is by means of frustrated
      internal reflection. Spacings and motions of the order of 0.05 wavelength are
      necessary which are difficult to control in the visible spectral region, but, in
      the 8-12 micro infrared region, the scale is twenty times greater, and a
      modulation cell based on this principle becomes quite practical. The
      characteristics of frustrated internal reflection are briefly summarized, and a
      modulation cell constructed on these principles is described. This cell has a
      clear aperture of 12.7 mm and produces 80% modulation of 10- micro radiation. A
      lead zirconate titanate piezoelectric stack is used for moving the frustrating
      element, which gives a frequency response higher than 6 kc/sec.

PMID- 20048792
TI  - Optical misalignment due to temperature gradients in electrooptic modulator
      crystals.
AB  - A possible source of misalignment of light in an optical communication system,
      utilizing electrooptic modulators, is the deflection of the light beam within the
      modulator crystal due to temperature gradients. The present paper investigates
      the light deflection resulting from a linear temperature gradient across various
      modulator crystals. The total effect is found to be the sum of two contributions,
      one due to the crystal expansion, the other due to the index of refraction
      gradient, and is found to be smaller, by the factor 10, in quartz than in KDP.
      The experimental method described provides also a simple way of determining dn/dT
      in crystals for both ordinary and extraordinary rays.

PMID- 20048793
TI  - A tunable birefringent filter.
AB  - A rotating-field phase shifter is described which permits continuous electronic
      tuning of birefringent filters over extended spectral regions. The use of such
      phase shifters reduces the conditions for tuning synchronism between all filter
      stages to a simple relationship between the electrical driving frequencies.
      Materials which exhibit a dual transverse electrooptical effect and no natural
      birefringence may be employed, and a number of suitable candidates are discussed.
      Also proposed is a modification of the classical Lyot filter which utilizes
      reflection-type elements between crossed polarizers. Such a design considerably
      reduces the number of optical components required by an adjustable filter of
      conventional form. The appropriate theory is given for both the simple-element
      and the split-element cases. It is shown that a filter of this type can be tuned
      successfully over a wide range of wavelengths if only certain of the phase
      shifter wave plates are achromatic. Fresnel rhombs are shown to be applicable as
      simple achromatic lambda/4 plates. A mechanically tuned four-stage filter has
      been constructed with reflection-type elements and Fresnel rhombs. Its
      performance was found to be in agreement with theory. The feasibility of
      electronic tuning is demonstrated by the results of frequency modulation
      experiments with a nitrobenzene Kerr cell and a circularly polarized electric
      field.

PMID- 20048794
TI  - Factors affecting the performance of commercial interference filters.
AB  - Measurements of the transmission characteristics of commercial narrow-band
      interference filters made by different manufacturers are described. The effect of
      angle of incidence on center wavelength, bandwidth, and maximum transmittance are
      shown to be important, and measurements on typical filters are compared with
      theory. Nonuniformity of transmission over the filter surface is shown to have a
      significant effect on the spectral quality and mean wavelength of the transmitted
      radiation. Variation of filter temperature from -60 degrees C to +60 degrees C
      resulted mainly in a wavelength shift in the transmission band of +0.1 A/ degrees
      C to 0.3 A/ degrees C with little change in form. The experimental results
      provide a basis for specification of the characteristics that are important in
      practical applications, and relatively simple mathematical expressions are shown
      to be useful in predicting some of the observed variations.

PMID- 20048795
TI  - Spectrum of a Fabry-Perot resonant cavity containing an active medium.
AB  - A Michelson interferometer has been used to measure the visibility curves for the
      6328 A neon emission line in a 90% He-10% Ne gas mixture in order to determine
      the effect of an optical cavity upon the line shape when the medium exhibits a
      net gain and yet the system is below lasing threshold. An analytical model for
      the effect of the cavity is proposed and a computer program set up to fit the
      model to the data. The cavity gain and finesse are used as variable parameters.
      The same techniques can be applied to a laser and the number of longitudinal
      lasing modes can be determined; however, in this case the gain and to some extent
      the finesse are indeterminate.

PMID- 20048796
TI  - Frequency control of a Nd(3+) glass laser.
AB  - It is found that laser emission can be obtained in narrow lines less than 0.1 A
      wide anywhere within a 130-A interval centered about the peak emission at 1.06 mu
      by the use of thin reflecting plates acting as wavelength-sensitive mode
      selectors. For a plate aligned perpendicular to the axis of the laser the
      emission is at those wavelengths at which the plate thickness is an odd number of
      quarter wavelengths. The plate tends to produce a spiking emission as a function
      of time and no loss in output energy.

PMID- 20048797
TI  - The effect of axial magnetic fields on gas lasers.
AB  - An expression is obtained for the intensity of polarized light transmitted
      through a laser amplifier and linear polarizer, as a function of the strength of
      an axial magnetic field. The result is compared with an experiment reported by
      Hotz in which it was claimed that the natural width of the laser transition was
      measured. The effect of applying a magnetic field parallel to the axis of a laser
      having plane-parallel windows is also considered. The variation in the frequency
      of beats between oppositely circularly polarized modes, as a function of magnetic
      field, is obtained. The result shows that an experiment performed by Culshaw and
      Kannelaud cannot be interpreted as a level-crossing effect as was previously
      supposed.

PMID- 20048798
TI  - Stimulated Raman effect in some tetrahedral molecules.
AB  - Stimulated Raman spectra have been excited in liquid SnCl(4) and in methane gas
      making use of a medium high-power ruby laser. The spectra have been photographed
      by means of a high-resolution grating spectrograph. The Deltagamma value
      approximately nu(1) for methane was found to be 2916.605 cm(-1) +/- 0.012 cm(-1).
      No detectable pressure shift was observed over a range of gas densities from 3
      amagat to 12 amagat. The stimulated Raman lines in methane are very sharp and
      only slightly broader than the laser line. In SnCl4 the first Stokes line
      consists of only a single component instead of the expected isotopic triplet. The
      half-intensity width of this line was found to be 0.5 cm(-1). At least 0.15 cm(
      1) of this line-width must be due to the stimulated Brillouin doublet since the
      threshold is lower for the stimulated Brillouin effect than for the stimulated
      Raman effect. The stimulated Brillouin effect was observed with a Fabry-Perot
      etalon. Measurements of the Fabry-Perot patterns gave a value of 840 m per see
      for the velocity of sound in SnCl(4) at 27 degrees C.

PMID- 20048799
TI  - A recording sampling system for measuring laser energy.
AB  - An apparatus has been designed and built which simultaneously measures the energy
      incident on a biological system which is being exposed to a laser beam. The
      advantages of the direct reading system are: (1) no attention is required of the
      laser operator, (2) a permanent record is produced, (3) true integration of the
      pulse train is accomplished, (4) high inherent accuracy, (5) in conjunction with
      a fast oscilloscope, it reproduces pulse waveforms with minimum distortion, and
      (6) calibration is simple and direct. Basically the system employs a fast high
      current capability photodiode, a high-quality integrating capacitor, an emission
      limited pump diode with a servo-motor amplifier combination for dark current
      balance. The photodiode cathode surface is S-1 so that both ruby and neodymium
      wavelengths 694.3 mmicro and 1060 mmicro, respectively, may be measured.
      Reproducibility is better than 3% when compared with a blackbody receiver (cone
      radiometer). A Tektronix 585A oscilloscope and P-80 cathode follower probe fitted
      with a 50-Omega load resistor can be plugged into the photodiode housing in place
      of the integrating capacitor for waveform observation and power-level
      measurements. Calibration on an absolute basis is easily accomplished by
      simultaneous comparison with a calibrated blackbody receiver (cone radiometer).

PMID- 20048800
TI  - Consideration of atmospheric turbulence in laser systems design.
AB  - The physical basis for various effects of atmospheric turbulence on laser systems
      is briefly discussed, and certain limitations of the theoretical results given by
      Tatarski are summarized. The most important conclusion is that Tatarski's results
      for amplitude and phase fluctuations, while they are not applicable for a laser
      beam of arbitrary diameter, do provide an adequate approximation when the beam
      diameter is at least a factor of 2 greater than the lateral correlation length
      for amplitude fluctuations, which is true in many applications. The effects
      analyzed in some detail are beam steering, beam spreading, image dancing, image
      blurring, scintillation, and phase fluctuations, certain of which are intimately
      related. As to specific applications, the signal-to-noise ratio for an AM signal
      passing through the turbulent atmosphere is derived in terms of the power
      fluctuation, and communication links are considered in terms of this ratio; the
      effect of power fluctuations on the probability of detection for the laser radar
      is discussed in general, and a special example is given; finally, the spot size
      on the moon's surface for a transmitter located on the earth's surface is
      calculated for different turbulence conditions.

PMID- 20048801
TI  - The absorption of laser radiation along atmospheric slant paths.
AB  - The absorption of laser radiation along atmospheric slant paths is calculated
      when Lambert's law is valid. Illustrative results are given for absorbing gases
      which are distributed uniformly throughout the atmosphere and when the
      temperature variation of the line intensities and half-width can be neglected.
      These results are then generalized to include cases of nonuniformly distributed
      gases with a temperature variation along the path. The effect of the overlapping
      of spectral lines is studied through the use of the Elsasser model. Finally, it
      is shown that large differences in the absorptance may occur between
      corresponding frequencies in the red and violet wings when there is a shift in
      the position of the line center with pressure. This line shift could ideally be
      studied with laser sources.

PMID- 20048802
TI  - Optical design considerations in photobleaching with cw lasers.
AB  - A new method is described which uses the stabilized output radiation of a cw
      laser as an exciting light source to study reversible and irreversible nonlinear
      absorption effects of organic dyes in aqueous solutions at high laser power
      densities. Design concepts which emerged from a closer study of the laser beam
      properties and its interaction with liquids are discussed. It is felt that this
      method is applicable not only for photolytic studies, but also in spectroscopic,
      spectrophotometric, and other experiments with cw lasers.

PMID- 20048803
TI  - A spectral radiometer for reentry measurements.
AB  - A radiometer specifically designed to measure the radiant power emitted by a
      reentry event is discussed. The measurement problem is presented. The optical
      design problem is evaluated. The result of a computer-designed optical
      configuration is given. The electronic circuits and data recording system are
      discussed, and the performance of the system is evaluated in terms of the
      measurement problem.

PMID- 20048804
TI  - Zero reflection from thin absorbing films on a metal base.

PMID- 20048806
TI  - Electron beam excitation in laser crystals.

PMID- 20048805
TI  - Laser-induced breakdown in oxygen gas at high pressure.

PMID- 20048807
TI  - Comments on the paper by A. J. Bevolo and W. A. Barker.

PMID- 20048808
TI  - Saturation of electroluminescent image-retaining panels by laser beams.

PMID- 20048809
TI  - Birefringence of natural quartz.

PMID- 20048810
TI  - Interferometric measurements using the wavefront reconstruction technique.

PMID- 20048811
TI  - A signal sampling photomultiplier circuit.

PMID- 20048812
TI  - Eight-channel polychromator to measure narrow transient spectral profiles in the
      ultraviolet.

PMID- 20048813
TI  - Comments on reciprocal-mode 2pi-sr-mirror reflectometers.

PMID- 20048814
TI  - Applied optics of optics and opticists.

PMID- 20048816
TI  - A laser end reflector with spectral tuning capability.

PMID- 20048815
TI  - Further remarks on "A numerical method for determining the relative spectral
      response of the vidicons in a nimbus satellite system".

PMID- 20048817
TI  - Optical methods of temperature measurement.
AB  - The history of the laws of thermal radiation is briefly reviewed, and the
      theoretical relations basic to some of the optical methods of temperature
      measurement are given. Comments on a number of optical methods are presented, as
      well as a selected reference with each method where more detail is available. In
      conclusion, several problems, in areas of uncertainty in the field of optical
      methods of temperature measurement, are suggested in the belief that a solution
      to these problems will greatly enhance the technical value of this field.

PMID- 20048818
TI  - On the possibility of excitation heating of ions to high temperature.
AB  - Cyclic or chainlike inelastic collision processes are invoked as an hypothesis to
      explain the grossly nonthermodynamic properties of energetic carbon and gas-fed
      carbon arcs confined by magnetic fields. Elastic collisions between the fast
      electrons (upsilon_ > upsilon(+) but E_ << E(+)) and the hot ions appear to be
      only about one-tenth as efficient a process for heating the ions as the proposed
      multiple inelastic collision process, which we call excitation-heating. In
      addition, a revised treatment of the rate of energy transfer from hot carbon ions
      to the very cold electrons (upsilon_ < upsilon(+)) reduces the conventional ion
      cooling rate by a factor of about 6.

PMID- 20048819
TI  - An evaluation of an high temperature blackbody as a working standard of spectral
      radiance.
AB  - For those interested in measuring the spectral radiance of high-intensity arcs,
      especially in the ultraviolet region, the 3000 degrees C blackbody has several
      advantages over the conventional tungsten ribbon filament standard of spectral
      radiance. At a wavelength of 250 nm, it is between two and three orders of
      magnitude more intense and could have 30% to 40% less uncertainty in its spectral
      radiance. Moreover, by using the blackbody, measurements could be extended to
      wavelengths shorter than 250 nm. On the other hand, the intensity advantage of
      the blackbody can be nearly eliminated by operating and calibrating a tungsten
      standard-type lamp well over its rated current. Tests have shown that the
      stability of these lamps operated at 45 A and 50 A is suitable for calibration
      purposes.

PMID- 20048820
TI  - Spectroscopic temperature profile measurements in inhomogeneous hot gases.
AB  - Temperature distributions in inhomogeneous hot gases were determined from line-of
      sight infrared spectral measurements. Radiance and transmittance of combustion
      products of flat flames were measured at each of several CO(2)-band frequencies
      near 4.3 micro. Measurements of isothermal samples showed how the CO(2)
      transmittance varied with temperature. Radiance measurements were made on samples
      with known nonisothermal temperature profiles. Radiance equations were so
      formulated that they could be solved for the temperature profile of the
      nonisothermal sample by an iterative procedure, using the transmittance and
      radiance data described above. Temperature profiles obtained by this procedure
      were in good agreement with the predetermined thermal structures of the
      specimens.

PMID- 20048821
TI  - Optical activities in industry.

PMID- 20048822
TI  - Measurements of temperature profiles at the exit of small rockets.
AB  - The sodium line reversal technique was used to determine the reversal temperature
      profile across the exit of small rockets. Measurements were made on one 73-kg
      thrust rocket, and two 23-kg thrust rockets with different injectors. The large
      rocket showed little variation of reversal temperature across the plume. However,
      the 23-kg rockets both showed a large decrease of reversal temperature from the
      axis to the edge of the plume. In addition, the sodium line reversal technique of
      temperature measurement was compared with an infrared technique developed in
      these laboratories.

PMID- 20048823
TI  - Optical temperature measurements in shock tubes from relative emission
      intensities.
AB  - A method is presented for obtaining spectroscopic temperatures in shock tubes
      using relative emission from two wavelength regions of a molecular band system.
      Experimental results are given for the OH violet system obtained in the reflected
      wave region near 3500 degrees K. These results show that equilibrium conditions
      prevail and that the spectroscopic temperatures agree with those calculated from
      shock wave velocities. A resume of the appropriate theoretical considerations is
      given along with a detailed discussion of the experimental techniques required. A
      brief discussion is also given of some other techniques used to measure
      temperatures in shock tubes, and comments are made regarding these methods as
      well as on some of the general problems associated with spectroscopic temperature
      measurements in shock tubes.

PMID- 20048824
TI  - Spectroradiometric pyrometry of shock-heated gases by infrared emission and
      absorption measurements.
AB  - A spectroradiometric pyrometer was developed to measure temperatures of shock
      heated gases with time resolution of about 10 microsec. Gas temperatures in shock
      heated CO(2)-N(2) mixtures and in self-sustaining detonations were determined by
      simultaneously measuring infrared spectral radiance and absorptance at selected
      wavelengths in CO(2) and H(2)O band spectra. By Kirchhoff's law, the ratio
      (radiance/absorptance) equals the Planck blackbody radiance, from which the
      temperature is easily found. The measured temperatures agreed with values
      calculated from the measured shock velocities.

PMID- 20048825
TI  - Transmission of infrared radiation from flames by CO(2).
AB  - The transmission of infrared radiation from flames through various pathlengths of
      CO(2) was determined in the laboratory. The results show that a considerable
      amount of flame energy is transmitted in the regions 2.5 micro to 3.5 micro and
      4.0 micro to 5.5 micro. For example, a cell length of 1500 cm of CO(2) at 760-mm
      pressure, equivalent to the CO(2) content in 50,000 m of atmosphere at sea level,
      transmitted 20% of the energy in the band region from 4.0 micro to 5.5 micro.
      Integrated transmittances for the bands at various pressures and cell lengths are
      presented in tabular form.

PMID- 20048826
TI  - An improved double-beam infrared microspectrometer.
AB  - The conversion of single-beam monochromators to double-beam microspectrometers is
      described. The principal advantage of the present system over others used is a
      great improvement in the long-term stability of the electronics; other advantages
      include simplicity, compactness, and complete freedom from beats due to mains
      frequency pickup. The system has been designed for use, in conjunction with a
      polarizer, for the examination of fibers, small crystals, and small areas of
      oriented biological macromolecules as well as for microsamples.

PMID- 20048827
TI  - A wide spectral range ultra-rapid scan spectrometer.
AB  - A grating spectrometer has been designed and built which allows extremely rapid
      scanning rates (over 200 A/ microsec) over a wide spectral range (4000-11,000 A)
      in one order with a theoretical resolving power of approximately 6000. The basic
      principles of the instrument are described together with some spectra (taken at
      speeds of approximately 90 A/microsec) illustrating its capabilities.

PMID- 20048828
TI  - Infrared spectral reflectance of some common minerals.
AB  - Infrared reflectance spectra of minerals of the carbonate, sulfate, nitrate, and
      silicate families exhibit spectral absorption band patterns that can be detected
      in reflection from surface minerals. These features could perhaps be used to
      identify such minerals from infrared reflection spectra of the moon and some
      planets; they might also be a source of confusion in interpretation of
      atmospheric spectra.

PMID- 20048829
TI  - Concepts and techniques of microwave optics.
AB  - The fast-developing domain of microwave optics is surveyed, with main emphasis on
      those aspects of interest to optical scientists. Special attention is devoted to
      the newer trends in that field of research. The following aspects are covered:
      diffraction theory of microwave optics, microwave optical instruments, beam
      waveguides, and components for millimeter waves.

PMID- 20048830
TI  - Mie scattering and absorption cross sections for absorbing particles.
AB  - The Mie scattering and absorption cross sections for spherical particles are
      calculated as a function of the complex index of refraction, n = n(1) - in(2).
      Curves of the efficiency factors for absorption, scattering, and extinction are
      given for n(1) = 1.01, 1.33, 1.5, and 2 and for n(2) = 10(-4), 10(-2), 10(-1), 1,
      and 10. The influence of the absorption on the efficiency factors is discussed.
      The results are compared with previously proposed simplified expressions for
      these factors. The variation of the scattered intensity with angle as n(2) is
      varied is illustrated in some typical cases. Finally the influence of n(2) on the
      narrow resonances which occur for large values of n(1) is discussed.

PMID- 20048831
TI  - Optical activities in the universities.

PMID- 20048832
TI  - Calculated slant-path absorption and distribution of atmospheric water vapor.
AB  - A procedure is described for determining the amount and distribution of water
      vapor along a slant path through the atmosphere above 13.7 km. A multilayer
      analysis is used in which the transmittance of each layer is calculated and the
      accumulative effect obtained at the altitude of observation. The method depends
      upon the contribution of each line to the absorptance in a finite spectral
      region.

PMID- 20048833
TI  - Correlation between atmospheric backscattering and meteorological visual range.
AB  - On the basis of our present knowledge of the distribution of natural haze
      particles in the atmosphere, the relation between backscatter intensity and the
      visual range, or the extinction coefficient, has been analyzed. It can be shown
      that the various processes which cause the changes in visibility (increasing
      particle number, changes in particle size distribution, etc.) result in rather
      different backscatter conditions. Only by a combination of such processes is it
      possible to explain a relation between backscatter and extinction coefficient as
      it can be derived from experimental data. It therefore becomes clear that such a
      relation cannot be a unique one and that it will change from one situation to
      another.

PMID- 20048834
TI  - Improvements to a source emitting a continuum from the visible to the soft x
      rays.
AB  - The authors describe the following improvements to a three-electrode vacuum spark
      source: reduction of the size of the triggering device, electronic control of the
      discharge rate, and a completely coaxial mounting of the electrodes along the
      optical axis. The performance thus obtained is specified, and absorption spectra
      are shown as examples of the use of the source in the far ultraviolet (100 A to
      2000 A).

PMID- 20048835
TI  - A photoelectric focus and seeing monitor for solar telescopes.
AB  - A solar focus and seeing monitor is described which utilizes the properties of an
      image of the telescope objective formed after putting a knife edge next to the
      solar limb. In a very simple way simultaneous measurements are obtained for the
      telescope focus and for the image motion and blurring produced by the earth's
      atmosphere.

PMID- 20048837
TI  - Anastigmatic cassegrain type telescope.
AB  - The 152-cm telescope of the Cerro Tololo Inter-American Observatory in Chile is
      to be made to a design producing images that are free of the usual Ritchey
      Chretien astigmatism. A 38-cm diam fused-quartz correcting plate is used to give
      a field diameter of 1. degrees 5, over which images are less than 0.5 see of arc
      in diameter.

PMID- 20048836
TI  - Ein Verfahren zur Beobachtung astronomischer Objekte mit hoher Auflosung und
      grosser Lichtstarke.
AB  - An observation method for astronomical objects is described which improves
      especially the angular resolving power and in some cases also the limit of
      detection. A modulator which is far away from a light detector modulates the
      light of the wanted object. Proper information handling enables the detector to
      decide between this light and the light of other objects. This method makes it
      possible to resolve details on the surface of fixed stars nearby the earth. The
      method can also be used to observe other physical phenomena which propagate like
      beams.

PMID- 20048838
TI  - Prime focus correctors involving aspherics.
AB  - The 380-cm Kitt Peak telescope will have an f/2.8 hyperbolic primary. Three
      tentative field correctors for prime focus use are described; they each have one
      or more aspheric surfaces.

PMID- 20048839
TI  - Applied optics of optics and opticists.

PMID- 20048840
TI  - Best-fit sphere approximation to a general, aspheric surface.
AB  - In manufacturing an aspheric lens or mirror, it is often convenient to generate a
      spherical surface as a starting point. The radius of the sphere should be such
      that the volume of glass which must be removed to achieve the final aspheric is a
      minimum. Equations for this best-fit sphere are developed and arranged in a form
      well suited for computer programming.

PMID- 20048841
TI  - Theory of concentric circular grid.
AB  - Any image-forming optical system is usually tested for aberrations by looking at
      the image plane. A point source is placed at some distance from the system (this
      may be a very large or small distance depending on the particular system) and its
      image by the optical system is studied by any of many methods available. The
      present paper presents the theory of a method in which a grating containing a
      series of concentric circles is placed at the image of the point source.
      Characteristic patterns are derived for the usual aberrations of optical systems
      and some typical photographs of these patterns are presented. Finally, this
      method is compared to the Ronchi test in which a series of straight lines are
      used for the grating.

PMID- 20048842
TI  - Interferometric measurement of large indices of refraction.
AB  - A method for determination of refractive indices which may be applied to thin
      flat plates of optical materials is considered. It is particularly suited for use
      with materials whose refractive indices are large (>1.8), but is not limited in
      the range of refractive index it can determine. The method uses an interferometer
      to measure the optical pathlength through a sample, and is shown to have moderate
      accuracy: +/-2 x 10(-4) in refractive index for a sample 0.5 mm thick. The effect
      of a nonideal sample is considered, and is shown to have only a small effect on
      the accuracy. The method has been applied to singlecrystal barium titanate in the
      visible spectrum, and tabulated results are given.

PMID- 20048843
TI  - OSA technical groups.

PMID- 20048845
TI  - The metric system.

PMID- 20048844
TI  - Photoelectrically induced free carrier absorption and amplification of light in
      cadmium sulfide.
AB  - It has been demonstrated that it is possible to control the intensity of visible
      and infrared light being transmitted through cadmium sulfide by controlled
      variations in photoelectrically induced free charge carrier densities which
      absorb the transmitted light. The free carrier optical absorption coefficient is
      extended to fit the case of photoelectrically induced free carrier absorption in
      semiconductors. This results in a theoretical modulation parameter which predicts
      the extent to which light transmission can be controlled by induced free carrier
      absorption. An experimental technique is presented which demonstrates that
      photoelectrically induced variations in the density of free carriers in CdS can
      indeed bring about a consequential control of the light transmission. Complete
      control over the transmission, in addition to light amplification by stimulated
      absorption, is demonstrated in CdS for both infrared and visible light between
      0.6 micro and 4.0 micro. Theoretically computed and experimentally observed
      values of modulation are in fair agreement, considering the limitation of the
      theory and the nature of the solid. The observed transmitted wavelength
      dependence in CdS is discussed on the basis of both the free carrier absorption
      theory and various photoconductivity mechanisms, and it is shown to be reasonably
      consistent with modern theory.

PMID- 20048846
TI  - A study in street lighting reflector design.
AB  - The solution to a problem in asymmetric reflector design for illumination is
      described. Working backward from a required rectangular and nonuniform light
      distribution pattern, the reflector geometry is arrived at by a combination of
      calculus and geometric construction. The central curve is computed from the
      general reflector equation lnR = tan (theta - d/2) dtheta, the integration being
      performed on an approximate matching function or graphically. The off-center
      contours are then obtained by means of an original drafting-board construction
      which is described, and the complete reflector shape is thus defined.

PMID- 20048847
TI  - 1.0621-micro He-Ne gas laser.

PMID- 20048848
TI  - Effect of ultraviolet pumping on ruby laser output.

PMID- 20048850
TI  - Calibration of an optical compensator by ellipsometry.

PMID- 20048849
TI  - A double slit with continuously variable separation.

PMID- 20048851
TI  - The far infrared transmission of polyethylene at reduced temperatures.

PMID- 20048852
TI  - Transmission of Irtran materials from 50 micro to 300 micro.

PMID- 20048853
TI  - Threshold for stimulated Raman spectra.

PMID- 20048854
TI  - Men and milestones in optics-IV. The first fifty years of the Optical Society of
      America.

PMID- 20048855
TI  - Staggered broad-band reflecting multilayers.
AB  - Considerable broadening of the reflectance band of a multilayer stack may be
      obtained by staggering the layer thicknesses in such a way that they form either
      an arithmetic or geometric progression. Results are shown for asymmetric and
      symmetric filters of 15, 25, and 35 layers. The presence of the narrowband
      transmission peaks exhibited by the symmetric filters is explained, and the
      advantages of the use of this type of filter as an interference filter is
      discussed.

PMID- 20048856
TI  - A radiometer-sonde for observing emission from atmospheric water vapor.
AB  - A balloon borne instrument is described which measures the downward flux of
      thermal radiation from atmospheric water vapor in the region of 6.3 micro. Use is
      made of a liquid-air-cooled gold-doped germanium detector together with a 40 cps
      vibrating vane chopper which operates at the same temperature as the detector.
      The responsivity of the detector increases with height, enabling measurements to
      be made over about four orders of magnitude. Signals, after amplification and
      synchronous rectification, are transmitted to the ground via an FM/FM telemetry
      system. Regular energy calibration is performed by reference to a local blackbody
      at a known temperature. The complete assembly weighs 2.5 kg and is flown on a
      conventional rubber balloon as part of a regular meteorological sounding. Twelve
      ascents have been made and measurements obtained up to 32 km. Results have been
      used to calculate stratospheric humidity profiles.

PMID- 20048858
TI  - Atmospheric transmission in the CO(2) bands between 12 micro and 18 micro.
AB  - Calculations have been made of high-resolution transmission in the CO(2)
      absorption bands between 12 micro and 18 micro by direct integration across the
      bands, for both homogeneous and atmospheric slant paths. Mixed Doppler-Lorentz
      broadening has been used at pressures lower than 100 mb. A method to eliminate
      the Curtis-Godson approximation has been developed and applied to the slant-path
      calculations. Comparisons have been made with previous theoretical and
      experimental data, and reasons for the discrepancies are discussed.

PMID- 20048859
TI  - Dispersion measurements on polytetrafluorethylene in the far infrared.
AB  - The reflection spectrum of polytetrafluorethylene has been determined in the far
      infrared over the range 22-143 micro by a Fourier method using observations made
      on a dispersive two-beam interferogram. The utility of the method, particularly
      when applied to the anomalous dispersion associated with a resonance absorption,
      is demonstrated, and values of the real and imaginary parts of the complex
      refractive index are determined. The relation between these parts of the index
      for the resonance at 202 cm(-1) (49.5 micro) agrees with the classical
      expectation of a circular plot in the complex plane.

PMID- 20048860
TI  - Far infrared study of the copper halides at low temperatures.
AB  - The far infrared spectra of the copper halides CuCl, CuBr, and Cul have been
      measured in transmission and in reflection at various fixed temperatures from
      room temperature to liquid-helium temperature. Marked changes of such parameters
      as resonance frquency and damping as a function of temperature have been
      observed, also a line-splitting in the case of CuCl. In addition, a considerable
      increase in the asymmetry of the transmission curves with decreasing temperature
      has been observed.

PMID- 20048861
TI  - Optical activities in industry.

PMID- 20048862
TI  - Far infrared transmission filters for the 300-18 cm (-1) spectral region.
AB  - A simplified method for the fabrication of crystal powder transmission filters is
      reported. Transmission filter combinations are described for the 300-18 cm(-1)
      spectral region. The application of these filters in a small grating spectrometer
      is demonstrated by water vapor spectra.

PMID- 20048864
TI  - Applied optics of optics and opticists.

PMID- 20048863
TI  - Unstable optical resonators.
AB  - A technique, firmly based on a development from ray optics, is presented for
      calculating the loss due to the finite sizes of curved mirrors when these form an
      unstable optical resonator. If paraxial rays launched within such a resonator are
      confined near the resonator axis, the resonator is termed stable; otherwise it is
      termed unstable, and is known to have high losses. Siegman has recently presented
      a geometrical method, brilliantly constructed ad hoc, for calculating these
      losses in unstable resonators, and indicated where these might be advantageous in
      laser application. The ray optical theory presented here, which employs the
      concept of ray modes in an equivalent beam waveguide, is shown to yield results
      equivalent to those of Siegman for all cases considered by him. However, being
      derived from conventional ray optics, the validity of the formulas is
      independently established, and these formulas are immediately applicable to re
      entrant resonators and resonators containing inhomogeneous media. The fractional
      loss per resonator pass is equal to 1-|lambda(2)|, where |lambda(2)| < this 1 is
      an eigenvalue of the transfer matrix T, representing the corresponding ray
      transformation.

PMID- 20048866
TI  - MICRO-65, International Symposium on Applied Microscopy, University of Sheffield,
      England, 6-9 July 1965.

PMID- 20048865
TI  - The relations between the axial aberrations of photographic lenses and their
      optical transfer functions.
AB  - The wave aberration of a photographic lens can be represented for an axial image
      point by means of three coefficients. The usual values of these coefficients are
      studied. The optical transfer function (OTF) is computed from the wave aberration
      by means of an analog computer and represented as a function of the size and the
      shape of the wave aberration. The influence of stopping down the aperture on the
      image quality is investigated.

PMID- 20048867
TI  - The modulation transfer function of an optical system with a rotationally
      symmetric circle of confusion.
AB  - The relationship between an optical system's circle of confusion and the quality
      of the image it forms is not specified by any universally accepted criterion.
      However, a simple geometric theory helps place the problem in perspective. As a
      first-order approximation, the circle of confusion is considered to be a
      uniformly illuminated disk. Then the illumination at a point in the image is the
      average of the illumination which would occur in the geometric image within an
      aperture of finite diameter centered at this point in the image plane. If the
      circle of confusion has a more complex radial illumination distribution, the
      image-forming process can be considered as the combined operation of a number of
      concentric averaging apertures of varying radii. If the circle of confusion has a
      Gaussian radial illumination distribution, a solution for the modulation transfer
      function can be obtained in closed form.

PMID- 20048870
TI  - We can safely set for a subscription.

PMID- 20048869
TI  - Optical design of wollaston-prism digital light deflectors.
AB  - The optical design of Wollaston-prism digital light-deflection systems is
      analyzed. It is found that the performance of the system is limited by (1) the
      diffraction spreading of the incident light beam, (2) the walk-off of the beam at
      the exit aperture, (3) the generation of spurious light, and (4) distortions in
      the angular deviation of each prism. The magnitude and functional dependence of
      these limitations are calculated, and criteria are supplied for the design of
      practical Wollaston-prism light-deflection systems. The design procedure is
      outlined, and numerical examples are given. The examples show that high-speed
      Wollaston-prism systems having a capacity of more than 10(6) bits are practical
      at the present time.

PMID- 20048871
TI  - A spherical mask to compensate for cos(3) and cos(4) illuminance variation.
AB  - A dyed or pigmented gelatin mask cast in a shallow spherical mold cavity can
      provide excellent compensation for the cos(3)alpha or cos(4)alpha fall-off of
      illuminance on a flat surface. Computed data are shown for the imperfection of
      correction under a variety of geometric conditions, and some typical applications
      are described.

PMID- 20048872
TI  - A null-balance vidicon spectrophotometer.
AB  - Automatic control theory was applied to the null-balance processing of spectral
      data generated by a vidicon television camera. The spectrum, after passing
      through reference and sample cells, was focused on the vidicon faceplate. The
      camera detects a single wavelength with each horizontal scan. The scan generates
      monochromatic dark reference, source reference, and sample signals. The voltage
      signals (video) are processed by a nonlinear null-balance loop. The loop computes
      the ratio (I/I(0))(gamma) at each scanned wavelength. gamma is a constant
      introduced by the vidicon light transfer characteristic. The train of horizontal
      scans generated in one vertical vidicon scan represents the scanned spectrum. The
      entire spectrum is thereby scanned without mechanical motion. The null-balance
      loop renders the spectrophotometer insensitive to changes in line voltage,
      amplifier drift, or shift in spectral sensitivity. The oscilloscope readout
      displays two horizontal lines representing 100% transmission and dark level as a
      function of wavelength. The sample absorption spectrum is traced between these
      two lines. (I/I(0))(gamma) is obtained by linear interpolation between these
      limits. gamma has a numerical value of less than unity and therefore tends to
      compress the photometric scale (I/I(0)). That is, the low light level signals are
      of larger amplitude than those of a linear scale. Gamma becomes a constant
      coefficient of the extinction coefficient and presents no problem in quantitative
      chemical analysis.

PMID- 20048873
TI  - OSA Technical Groups.

PMID- 20048874
TI  - Flat-field spectrograph camera designs.
AB  - The final designs for the short-focus spectrographic cameras for the 213-cm Kitt
      Peak reflector are here defined. Duplicates of some of these cameras will be used
      also on the 152-cm telescope of the Cerro Tololo Inter-American Observatory in
      Chile.

PMID- 20048876
TI  - Detection of low angle optical scattering by Fabry-Perot resonance.

PMID- 20048875
TI  - Precision mapping of pairs of uncoated optical flats.
AB  - The essential features of apparatus suitable for routine mapping of pairs of
      wedged uncoated optical flats are described. In this method the aperture of the
      pair of flats is scanned in a regular pattern, and information about the spacing
      uniformity is derived from the interference of light reflected from the flat
      surfaces. Accuracies within about lambda/500 are obtained.

PMID- 20048877
TI  - An interesting infrared planet horizon sensor design.

PMID- 20048878
TI  - Tuning fork choppers for infrared spectrometers.

PMID- 20048879
TI  - Inexpensive water-insoluble window material for the 16 micro to 21 micro
      wavelength region.

PMID- 20048880
TI  - A hybrid narrow band filter.

PMID- 20048881
TI  - A precision all-purpose optical tester.

PMID- 20048882
TI  - Experimental confirmation of standing waves in laser resonators.

PMID- 20048883
TI  - Optical tracking; a brief survey of the field.
AB  - A survey on the topic of optical tracking is presented. This includes system
      considerations, techniques, categories, and applications currently utilized in
      the field of optical tracking. In addition, a brief historical description is
      included.

PMID- 20048884
TI  - Vidicon star tracker.
AB  - In many applications of star trackers, extremely short acquisition times, as well
      as accuracy and sensitivity, are required. Tracking systems employing the vidicon
      as a radiation sensor have been shown to provide the necessary speed of
      acquisition for such applications. This paper discusses the various theoretical
      and practical considerations involved in using the vidicon as a sensor in a star
      tracking system. A typical system configuration including telescope, sensor, and
      processing electronics is presented. The various optical and sensor parametric
      relationships required in the design of a vidicon star tracker are fully
      discussed and analyzed.

PMID- 20048885
TI  - Digital laser ranging and tracking using a compound axis servomechanism.
AB  - Optical systems for tracking and ranging have advantages over other systems
      because of the inherent spatial efficiency of optical frequency energy. Plane
      polarized, coherent laser beams provide a control of optical energy not
      previously available. Utilizing laser light, this system gives precise tracking
      and slant-range information at a real-time sampling rate of 200 c/s. A compound
      axis servo system, made possible by a mirror system mounted on a tracking
      pedestal, provides angular data by tracking a laserilluminated retroreflector
      mounted on the target. Slant range to the retroreflector is determined by a
      digital-mode, frequency-modulated, cw-laser ranging system, whose resolution and
      sampling rate are under independent control.

PMID- 20048886
TI  - Survey of infrared trackers.
AB  - A summary of the method of operation, performance characteristics, and
      applications of existing infrared tracking devices is presented for all systems
      described in accessible literature. Seekers, or devices for homing and system
      guidance, are specifically excluded. Applications are discussed from the
      standpoint of important physical considerations, i.e., target size and spectral
      radiance, background radiance, etc., a summary table of existing system
      characteristics is included, and three graphs of performance of three actual
      systems are presented.

PMID- 20048887
TI  - Our former managing editor, MissWakeling.

PMID- 20048888
TI  - Precision laser automatic tracking system.
AB  - A precision laser tracker has been constructed and tested that is capable of
      tracking a low-acceleration target to an accuracy of about 25 microrad root mean
      square. In tracking high-acceleration targets, the error is directly proportional
      to the angular acceleration. For an angular acceleration of 0.6 rad/sec(2), the
      measured tracking error was about 0.1 mrad. The basic components in this tracker,
      similar in configuration to a heliostat, are a laser and an image dissector,
      which are mounted on a stationary frame, and a servocontrolled tracking mirror.
      The daytime sensitivity of this system is approximately 3 x 10(-10) W/m(2); the
      ultimate nighttime sensitivity is approximately 3 x 10(-14) W/m(2). Experimental
      tests were performed to evaluate both dynamic characteristics of this system and
      the system sensitivity. Dynamic performance of the system was obtained, using a
      small rocket covered with retroreflective material launched at an acceleration of
      about 13 g at a point 204 m from the tracker. The daytime sensitivity of the
      system was checked, using an efficient retroreflector mounted on a light
      aircraft. This aircraft was tracked out to a maximum range of 15 km, which
      checked the daytime sensitivity of the system measured by other means. The system
      also has been used to track passively stars and the Echo I satellite. Also, the
      system tracked passively a +7.5 magnitude star, and the signal-to-noise ratio in
      this experiment indicates that it should be possible to track a + 12.5 magnitude
      star.

PMID- 20048889
TI  - The effect of scintillating target intensity upon the performance of a pulse
      position modulation optical tracker.
AB  - A prominent noise source encountered in guidance systems based upon daytime
      optical tracking of targets near the ground is the fluctuation in received target
      irradiance caused by atmospheric scintillation. The scintillation observed can be
      reduced somewhat by appropriate optical design; however, the associated signal
      processing system must still operate upon a scintillating input signal. Thus, it
      becomes essential to understand the manner in which scintillation affects the
      signal-processing performance. If the tracker is of a type which codes the target
      position into the arrival time of an electrical pulse, the influence of the
      atmospheric scintillation is made manifest through random variations in both the
      amplitude of the signal pulse and its shape. The effect of these random
      variations upon the performance of a specific type of signal-pulse processing is
      derived in some detail, and calculations of the variance in the measured signal
      pulse arrival time are presented. Detection probability and false alarm
      probability are also presented as functions of the atmospheric scintillation
      index.

PMID- 20048890
TI  - A practical method for sensor absolute calibration.
AB  - This paper describes a method of performing sensor calibrations using an NBS
      standard of spectral irradiance. The method shown, among others, was used for
      calibration of the Mariner IV Canopus sensor. Agreement of inflight response to
      preflight calibrations performed by this technique has been found to be well
      within 10%.

PMID- 20048891
TI  - A direct-reading comparison spectroradiometer.
AB  - A modification of the Cary Model 14 for radiometry is described which allows
      recording in microwatts per square mlllimeter per nanometer on the ordinate and
      linear wavelength on the abscissa through the range 250-2500 nm. A 5.08-cm diam
      rotating integrating sphere is used to compare standard to unknown sources at a
      30 c/s rate. The undispersed radiation from the sphere is directed through the
      entrance slit of the monochromator. After dispersion by the monochromator the
      energy is received by a single phototube or PbS detector as alternate pulses of
      standard and unknown energy. This design results in common optical elements
      throughout the instrument except for the standard and unknown sources themselves.
      An electrical calibration system permits an ordinate scale reading irradiance
      directly in microwatts per square centimeter per nanometer with simple provisions
      for range change. The instrument provides a dynamic range of 2 x 10(6) to 1. A
      large open area is provided for mounting unknown sources. The entrance optical
      system is designed so that remote sources can be viewed conveniently.

PMID- 20048892
TI  - Scanning spectrometer of the gillieson type.
AB  - A new type of plane grating monochromator has been devised in which the grating
      is illuminated by convergent light. The main feature of this design is an
      arrangement by which the grating is simultaneously translated and rotated by
      means of a simple rotation about an axis displaced from the grating face. The
      motion is such that the spectrum remains in good focus on a fixed exit slit over
      a range of wavelengths from zero order to 5000 A in the third order for a grating
      with 600 lines/mm. This type of mount has the advantages of small aberrations and
      small astigmatism over the usable range. Because there are only two reflections,
      the instrument is best suited for studying problems where low light level might
      be of concern, such as for astronomical work or for use in the far ultraviolet.

PMID- 20048894
TI  - Optical activities in the universities.

PMID- 20048893
TI  - The measurement of the temperatures of molecules in cool stars.
AB  - The spectra of red stars display a complex profusion of atomic and molecular
      absorption lines and bands. The overlapping of successive absorptions is so
      severe that the usual methods of temperature measurement cannot be applied.
      Instead, an indirect procedure has been attempted involving the calculation of a
      theoretical absorption profile based on a simple model, and comparison with
      observation. The results show that the detailed stellar profile is relatively
      insensitive to excitation temperature, so that this particular stellar parameter
      is relatively uncertain.

PMID- 20048895
TI  - Near infrared scattering by sunlit terrestrial clouds.
AB  - Absolute intensity (radiance) spectra of solar radiation scattered by clouds were
      obtained in the 1.15-micro to 3.6-micro region as a function of cloud type, cloud
      altitude, and scattering angle. The angular dependence of cloud scattering was
      determined at a number of wavelengths between 1.15 micro and 3.6 micro. From 2.6
      micro to 2.9 micro, here water and ice are strongly absorbing and single
      scattering dominates, scattering efficiency increases nearly tenfold as the
      scattering angle decreases from 150 degrees to 45 degrees , in agreement with
      theory. At shorter and longer wavelengths, scattering efficiency increases by
      about a factor of three over the same range of scattering angles. Characteristic
      minima are observed in spectra of ice clouds at 1.5 micro, 2.0 micro, and 2.8
      micro, which are related to absorptions in the bulk material at the same
      wavelengths. The 1.5-micro and 2-micro minima are absent in spectra of liquid
      water clouds, even though the absorption characteristics of bulk water and ice
      are very similar. The differences in scattering behavior are explained on the
      basis of particle size.

PMID- 20048896
TI  - Uncertainties in the optical constants determined from isoreflectance curves.
AB  - The determination of optical constants by the isoreflectance method with
      polarized light is discussed. We consider uniaxial as well as isotropic
      materials. It is shown that the precision of the optical constants determined by
      the intersection of isoreflectors declines with increasing n and k because the
      curves intersect at small angles. Therefore, highly accurate measurements of
      reflectance are called for. The parallel mode of polarization is found to produce
      more precise results than the perpendicular mode. For uniaxial substances,
      however, the optical constants for the extraordinary ray can only be determined
      from the perpendicular mode.

PMID- 20048897
TI  - The elliptical polarization of light scattered by a volume of atmospheric air.
AB  - The scattering of linearly polarized light by aerosol particles produces partly
      polarized light whose ellipticity is theoretically and experimentally
      investigated for the specific case of a continental atmospheric aerosol in a
      volume of air. With the Mie theory and under the assumption of various aerosol
      size-distribution models, the ellipticity has been computed as a function of the
      scattering angle for various wavelengths. The computations have been based upon
      complex indices of refraction: M = 1.5-0.0i, M = 1.5-0.0li, M = 1.5-0.li, M =
      1.44-0.0i, M = 1.4-0.0i, M = 1.33-0.0i. The comparison between computed and
      measured values for the wavelengths of lambda = 0.45 micro to lambda = 0.65 micro
      discloses for dry aerosol a real part of the refractive index m = 1.50 and an
      imaginary part 0.01 <or=5 k > 0.1. With moist aerosol, the real part of the
      refractive index as well as the imaginary part decreases.

PMID- 20048899
TI  - Of optics and opticists.

PMID- 20048898
TI  - Sensitivity of an image intensifier film system.
AB  - Using calibrated light sources, the sensitivities of several commonly used films
      have been determined in terms of the number of photons incident required to
      develop one grain of emulsion. By incorporating an image intensifier in the
      system, the time required to obtain an image of a given quality or information
      content can be reduced significantly. Criteria are discussed whereby an estimate
      of the time advantage can be made for various experimental conditions. Noise,
      quantum fluctuations, spatial resolution, and over-all detection efficiency are
      discussed.

PMID- 20048900
TI  - A method for the measurement of optical retardation angles near 90 degrees.
AB  - A method is described for the calibration of a nonexact quarter-wave plate. This
      method makes use of the sensitive dependence on the retardation angle, for
      retardation angles near 90 degrees , of the functional relation between the
      orientation of the quarter-wave plate optical axis and the orientation of the
      polarization ellipse major axis, both with respect to the axis of the initial
      linear polarizer.

PMID- 20048901
TI  - Correction of lens aberrations by means of holograms.
AB  - Holograms are made of a wavefront emerging from a lens having spherical
      aberration. The hologram, when used in combination with the lens, serves as a
      corrector plate for the lens. Experimental results are given, followed by a third
      order analysis.

PMID- 20048902
TI  - Surface-deformation measurement using the wavefront reconstruction technique.
AB  - This paper describes a new method for the measurement of minute deformations of
      arbitrary three-dimensional objects, such as might occur due to applied stress.
      The method is an application of the wavefront reconstruction technique, as
      developed by Leith and Upatnieks, to the interferometry of three-dimensional
      diffusely reflecting objects. The theory of wavefront reconstruction is sketched.
      A detailed theory for the interpretation of the interference phenomena observed
      in terms of the translations and rotations undergone by a point on the object is
      presented. Experimental results verifying the method and the theory are shown.

PMID- 20048903
TI  - Some further aspects of scatter-fringe interferometry.
AB  - It is shown that an interferometer using one scatter plate and a plane mirror is
      well suited for testing long focus optical systems. Stability is automatically
      achieved in this system because of its +1 magnification. Two methods of
      introducing straight fringes into the field in order to examine a nearly perfect
      optical system, and a method of making scatter plates to give high-contrast
      fringe patterns are described.

PMID- 20048904
TI  - Application of interferometry to the measurement of the pitch of threads on a
      lead screw.
AB  - A rapid, interferometric method for measuring the pitch of a nonrotating lead
      screw that involves no mechanical contact with the thread is described. The
      moving plane mirror of a Michelson interferometer is set on the axis of the lead
      screw. The lead screw is mounted on the carriage of a machine which moves it
      parallel to its axis. The Michelson fringes are counted continuously as the screw
      threads are moved across a light beam. The Michelson interferometer uses the
      green line of a (198)Hg isotope electrodeless lamp. The passage of a pitch point,
      to punctuate the fringe count, is sensed by photoelectric microscopes, and
      associated electronic circuitry, as described herein. The performance of the
      apparatus is presented.

PMID- 20048905
TI  - Rotational-shearing irnterferometry.
AB  - A brief review of lateral- and radial-shearing interferometry is presented
      together with a thorough discussion of the theory of rotational-shearing
      interferometry. A rotational-shearing interferometer is described based on the
      Jamin principle that was built by the authors while at the Institute of Optics at
      the University of Rochester in Rochester, New York. Graphs and photographs of the
      interference patterns of the lenses and a lightweight mirror that were tested
      with this interferometer are presented and discussed. Finally, the effect of the
      size of the source on the degree of coherence of the interference pattern is
      considered.

PMID- 20048906
TI  - Dynamic optical path distortions in laser rods.
AB  - Measurements were made of the thermally induced distortions occurring in laser
      rods as a result of flash lamp heating. Time-resolved interferograms were
      obtained by placing the sample in a Mach-Zehnder interferometer and utilizing a Q
      switched laser as the interferometer-illumination source. It was observed that
      significant distortions occur during the pumping pulse leading to diverging-lens
      effects in the sample rods.

PMID- 20048907
TI  - Laser pumping by intense discharges in z-pinch geometry.
AB  - Optical properties of high-current, low-pressure, noble-gas discharges in z-pinch
      geometry are studied and compared with theta-pinch discharges and standard
      commercial light sources. Results indicate possible usefulness in systems where
      high peak power, high repetition rates or high uv content are demanded.

PMID- 20048908
TI  - Thermal distortion of diffraction-limited optical elements.
AB  - Recent developments of laser materials have advanced the state of the art to a
      point where the optical quality of many of these materials is approaching the
      diffraction limit. Using such components in a laser does not necessarily
      guarantee the generation of diffraction-limited laser beams. One of the severe
      problems is thermal distortion introduced in the optical cavity by the flash
      lamps. Ruby and glass lasers require a minimum of 0.6 J of heat deposition per
      joule of population inversion. Typical figures are 4-6 J per joule of population
      inversion.(1) Nonuniformities in the deposition of this heat cause optical
      distortions which virtually preclude diffraction-limited laser operation even if
      the materials themselves are of diffraction-limited optical quality. This paper
      will investigate these thermal effects in detail, and the relative sensitivity of
      a variety of materials to nonuniform energy depositions will be discussed. Water
      close to its point of maximum density and a certain special type of glass known
      as Pockels glass will be shown to have properties of particular interest for use
      in diffraction-limited lasers.

PMID- 20048909
TI  - Anomalous fluorescent decay of LiF:UO(3) under high-intensity excitation.
AB  - Single crystal samples of LiF:UO(3) were tested for laser action. While no
      unambiguous evidence for laser oscillations was observed, the material did show
      anomalous fluorescent decay under the highintensity pumping in basically two
      respects: (1) a short-lived (20-microsec to 30-microsec) micro-spike was
      exhibited, followed by (2) a period of unusually slow decay. To explain the
      observations, a depopulation mechanism is proposed and discussed.

PMID- 20048910
TI  - Effect of multiple reflections on the design of an elliptic cavity for solid
      state lasers.
AB  - The effects of multiple reflections in an elliptic reflector are investigated.
      The emphasis is on matching the absorption spectrum of laser crystals to laser
      pumps by increasing the effective absorption coefficient in areas of low
      absorption. It is shown that in an ideal case the pump power that would normally
      be lost, because of a low absorption coefficient of the crystal, can be regained
      by multiple reflections from a highly reflective elliptic cylinder. This gain is
      somewhat reduced by refraction of the rays by the crystal and flashlamp. An
      optimum condition for minimizing the refraction losses is derived including the
      effects of multiple reflections.

PMID- 20048911
TI  - Dynamic measurements of phase shifts in laser amplifiers.
AB  - Optical length variations in laser amplifier rods have been studied using two
      interferometers and the coherent 6328 A output from a helium-neon laser for the
      probe beam. The phase shifts measured during the excitation or pump period amount
      to many pi radians even for short (0.6 cm) and moderately pumped rods of ruby and
      neodymium glass. The results indicate the predominantly thermal nature of these
      pump-induced phase shifts.

PMID- 20048912
TI  - A dc-biased Kerr cell light modulator.
AB  - A dc-biased Kerr cell light modulator has been operated continuously at 5 Mc/sec.
      An analysis has been made showing the generation of harmonics as a function of
      applied bias and rf voltages. This shows how these may be chosen to optimize
      generation of a selected harmonic. Experimental data in excellent agreement with
      theory have been obtained. Modulation in excess of 50% at first harmonic has been
      obtained with f voltages of the order of 15% of the dc extinction voltage.

PMID- 20048913
TI  - Experimental and theoretical investigations of the spontaneous infrared radiation
      fluctuations of a high-pressure, high-current argon discharge.
AB  - The equations describing the spontaneous fluctuations of photon radiation are
      given by the Bose-Einstein statistics. These equations are applied to calculate
      the statistical fluctuations of photon radiation emitted by a nonhomogeneous
      plasma. By using a photodetector, the radiation fluctuations are transformed into
      corresponding output current fluctuations. The detector must have special
      properties as to sensitivity, noise, frequency response, and transmission
      characteristics. The InSb photodetector described here has the required
      properties. As a radiation source, the plasma of a stationary argon arc discharge
      at high pressure was used. By measuring and calculating the continuous photon
      radiation, it is possible to determine the temperature distribution in the
      plasma. Investigations of the electrical conductivity confirm the temperature
      distributions. Because of the high temperatures, as well as the sufficient
      optical thickness in the infrared spectral range, determination of the
      fluctuation factors is made possible. Considering the experimental difficulties,
      the agreement between measured and calculated factors is good. Instabilities in
      the plasma have been considered and eliminated in the experimental procedure.

PMID- 20048914
TI  - Copying holograms.

PMID- 20048915
TI  - Thermoplastic xerographic holography.

PMID- 20048916
TI  - Adjustment of narrow-band ultraviolet Fabry-Perot interferometers.

PMID- 20048917
TI  - Generation of a hologram from a moving target.

PMID- 20048918
TI  - On Moire fringes as Fourier test objects.

PMID- 20048920
TI  - The FM laser and optical communication systems.

PMID- 20048919
TI  - Measurement of the modulation of square wave targets in incoherent light.

PMID- 20048921
TI  - Reflector-light source requirements for homogeneous format illumination in night
      aerial photography.

PMID- 20048923
TI  - A double grating monochromator with no tracking error.

PMID- 20048922
TI  - On "Microwave models of optical resonators".

PMID- 20048924
TI  - Ritchey Chretien corrector system.

PMID- 20048925
TI  - Spontaneous Brillouin scattering in gases.

PMID- 20048926
TI  - Perspective rendering of the field intensity diffracted at a circular aperture.

PMID- 20048927
TI  - Some comments upon current optical shop practices.
AB  - The fabrication of optical elements began as an art rather than a science and has
      tended to remain so throughout its history. Today's methods are largely
      extensions of the original techniques. With spaceage demands for rapid response
      as well as quality, some effort is being made to remove optical technology from
      the realm of wizardry by standardizing fabrication procedures and associated
      working materials. However, the diversity of problems encountered in modern
      optical fabrication requires a flexibility of approach which indicates that the
      artisan will always be with us. Examples of some optical fabrication and testing
      procedures employed at the Goddard Space Flight Center are presented.

PMID- 20048929
TI  - Lens making for scientific instrumentation in the seventeenth century.
AB  - With the invention of the telescope and the microscope early in the 17th century,
      the production of optical lenses became an important factor in the development of
      these instruments for scientific observation and investigation. In spite of
      improvements in equipment and techniques, the obstacles to the production of
      suitable lenses were not surmounted until the 18th century because of lack of
      knowledge of the optical properties of lenses, and the difficulties in producing
      glass of suitable clarity due to primitive grinding and polishing techniques. The
      early astronomical lenses were produced by means of the primitive equipment of
      the mirror makers and polishers of pietre dure in Murano and Venice. The first
      professional apparatus for lens grinding and polishing was developed by Ippolito
      Francini of Florence, and subsequently improved by Eustachio Divini and Carlo
      Antonio Manzini. A major advance in the equipment and techniques was made by
      Giuseppe Campani of Rome in the second half of the century. Other important
      contributions were made by Christiaan Huygens in Holland and John Marshall in
      England. Toward the end of the 17th century, craftsmen in England and France made
      great strides in the improvement of apparatus and techniques for lens grinding
      and polishing. In spite of them, however, optical workshop practice improved
      extremely slowly, and it remained virtually unchanged into the 19th century.

PMID- 20048930
TI  - Measurement techniques used in the optics workshop.
AB  - Measurement techniques used in the optics workshop often are complex and
      demanding. Characteristics considered are flatness, parallelism, angularity,
      curvature, length, and surface quality. Types of measuring equipment common to
      the workshop and their relative accuracies are discussed. The present usage of
      the Kosters prism as a workshop measuring device is also discussed.

PMID- 20048931
TI  - Some effects of aerospace thermal environments on high-acuity optical systems.
AB  - The effects of the major features of an aerospace thermal environment on the
      principal components of large-aperture photographic catadioptric systems are
      considered. First approximation solutions to the focal shift and on-axis
      wavefront aberration produced by heat fluxes in windows (or corrector plates) are
      presented. The effects of axial heat fluxes and uniform temperature changes on
      mirror structures representative of current practice in lightweight-mirror
      technology are examined, and first approximations to the deformations of simple
      slab mirrors, Kanigen-coated metal mirrors, and sandwich-plate construction are
      derived. Some conclusions on the comparative utility of Kanigen-coated beryllium
      mirrors and solid or egg-crate fused-silica mirrors are drawn.

PMID- 20048933
TI  - Making corrector plates by Schmidt's vacuum method.
AB  - The theory and procedure are given for figuring corrector plates for Schmidt
      cameras and related systems following Bernhard Schmidt's classic method. The
      figure is achieved while the plate is deformed with a partial vacuum on one side.
      The method easily yields zone-free plates. A modification is described here
      wherein the correct profile is obtained without precise knowledge of the Young's
      modulus or Poisson ratio of the particular glass disk in hand. The method is
      recommended for systems of f/2.5 or slower as there is danger of the plate
      breaking for faster systems.

PMID- 20048934
TI  - Null test for wright telescope mirrors.
AB  - The Wright telescope is a variation of the Schmidt design which uses a corrector
      plate at the focus and whose primary mirror is an oblate spheroid. A null test
      for the mirror is described, which is a modification of the Foucault test, and
      which makes use of the properties of a particular reference ellipse.

PMID- 20048935
TI  - Electroforming of large mirrors.
AB  - Thin metal mirrors are prime candidates for space applications, because of their
      high thermal conductivity, low weight, and ability to withstand vibration during
      launch. Of all the fabrication processes, at the present state of the art,
      electroforming appears the most suitable for producing accurate, thin, metal
      mirrors with satisfactory mechanical and physical properties. Great strides were
      made over the past two years in precision electroforming. These are described
      along with General Electric's spincasting process for the fabrication of masters.

PMID- 20048936
TI  - Calculation of surface distortions of rotating mirrors and their effect on streak
      camera resolution.
AB  - The time resolution of streak cameras is limited by aberrations introduced by the
      rotating mirror. The effect of geometrical distortions of the mirror, rotating at
      maximum speed, may be minimized by appropriate choice of mirror material and
      cross section. The stresses in the rotating mirror and the distortions of its
      reflecting surface were calculated for various geometries of the mirror. By using
      a semianalytical point-match method, the same numerical scheme and the same
      formulas were applicable to all geometries. Sufficient data on the behavior of
      symmetric and partly symmetric cross sections have been obtained to permit
      optimization of the mirror design.

PMID- 20048937
TI  - The metric system.

PMID- 20048938
TI  - The slumping of optical surfaces during coating.
AB  - Slumping of optical surfaces takes place while antireflection substrates are
      being coated at 205 degrees C. Greater slumping is experienced at higher
      temperatures. Optical glasses held in kinetic-designed holders exhibit variable
      memories of reslumping. Glass elements held in nonkinetic and kinetic holders are
      compared at 205 degrees C.

PMID- 20048939
TI  - Air gauge measurement and driven lap polishing in the production of aspheric
      surfaces.
AB  - The increased demand for aspheric surfaces in optical systems has required
      refinements and advances in optical shop technology. Air gauges have been used to
      measure aspheric surfaces in prepolished and polished conditions to accuracies on
      the order of one wavelength of visible light. Small, synchronously driven laps
      have been used in the polishing and figuring of aspheric surfaces with good
      results regarding speed, accuracy, and smoothness. Both techniques provide
      interesting possibilities for future development.

PMID- 20048940
TI  - Simple aspherical surface generator.
AB  - This paper describes a method of grinding a concave mirror to produce a
      prescribed aspheric contour. It also describes polishing and figuring procedures.
      The method was applied to produce a relay optical system that relayed the image
      of the planet Venus, at the same time correcting aberrations. The image relayed
      was formed by an uncorrected spherical primary telescope mirror. The relayed
      image was located at the center of curvature of the mirror. The image here was
      substantially free of spherical aberration.

PMID- 20048941
TI  - Aspherics and surface generation; curve generation on a blanchard.
AB  - Techniques used to produce aspheric and other irregular curves are described in
      this article. Although the machinery is not unique, the manner in which it is
      applied is felt to be unusual. Typical of the many challenging jobs this company
      has produced was the grinding and polishing of numerous massive
      radiationshielding windows. These windows had a density of 3.2. Their physical
      dimensions were 2.1 m by 2.6 m by 125 mm thick. The weight of these windows was
      1915 kg. A description of the equipment and techniques used will be given in a
      future article.

PMID- 20048942
TI  - Of optics and opticists.

PMID- 20048943
TI  - Electrophotooptical technician training at Foothill College.
AB  - The critical steps in establishing a curriculum for a two-year program in
      electrophotooptics training of technologists are reviewed as initiated at
      Foothill College, Los Altos Hills, California.

PMID- 20048944
TI  - An autocollimation measurement of the right angle error with the help of
      polarized light.
AB  - In the paper a new method of the sign establishment for the right-angle deviation
      error in prisms is described. The method has been developed on the basis of the
      known autocollimation method of rightangle control and consists of introducing
      polarized light. Some examples of how to establish the rightangle deviation error
      sign are given.

PMID- 20048945
TI  - Automatic ellipsometer. Automatic polarimetry by means of an ADP polarization
      modulator III.
AB  - An analytical and experimental study of an automatic ellipsometer is reported.
      The polarized beam is modulated simultaneously by two ADP cells, and the
      corresponding two signals are separated and are used to adjust polarizer and
      analyzer settings in any of the four zones. The reproducibility of the setting
      has been demonstrated to be of the order of 0.01 degrees.

PMID- 20048946
TI  - Selection and processing of infrared materials.
AB  - The similarities and differences between specifications and fabrication
      techniques for optical glass and for ir materials are discussed. A general
      familiarity with this subject as applied to the visible region is assumed. Of the
      many materials known to transmit ir radiation, a group of nine is selected for
      emphasis; reasons are given for this selection, and specific comments made on
      each material. Those suggested for general use are germanium, silicon, arsenic
      trisulfide, KRS-5, Irtran-2 and -4, and for restricted uses strontium titanate,
      Irtran-1, and indium antimonide.

PMID- 20048947
TI  - The optical constants of some oxide glasses in the strong absorption region.
AB  - The optical constants n and k have been calculated for fused silica, three
      silicate glasses, and a phosphate glass from reflectance measurements made in the
      strong absorption region, from about 7 micro to 13 micro. Plots of the 2nkv
      product, which corresponds to the conductivity, as a function of frequency are
      used to determine the location of the resonance frequencies in the infrared.

PMID- 20048948
TI  - Duration and intensity of the radiation pulse from a flash tube.
AB  - The peak current, power, and half-peak duration of the current through a flash
      tube are determined. The flash tube may be considered as an element in an R-L-C
      circuit whose electrical behavior is dependent on a single parameter. The
      variation of tube current with voltage is examined and the plasma impedance
      determined. The intensity, rise time, decay time, and half-peak duration of the
      radiation pulse are determined for a range of tube geometries and gas pressures.
      The duration of the radiation pulse depends on that of the current, but the
      intensity is dependent on both gas pressure and power density.

PMID- 20048949
TI  - Zenith skylight intensity and color during the total solar eclipse of 20 July
      1963.
AB  - The zenith skylight intensity was measured, with a resolution of 10 A, over the
      wavelength range from 5200 A to 6400 A during a total solar eclipse at Hermon,
      Maine. The intensity was found to change by about two orders of magnitude in the
      2-min period before totality and reached a minimum during totality of 19.5 kR/A
      at 5200 A. The spectral distribution remained that of the day sky until the sun
      was more than 99.8% obscured. During totality, the shorter wavelengths were
      enhanced, indicating a shift to the blue in sky color. Comparisons with an
      independent measurement from an aircraft show that the intensity scale height of
      the secondary scattered component, predominating at totality, is significantly
      less than that of the day sky. The measurements are compared with the day and
      twilight sky.

PMID- 20048950
TI  - Sky luminances and the directional luminous reflectances of objects and
      backgrounds for a moderately high sun.
AB  - Sky luminance distributions for the upper and lower sky at ground level, 1.52 km
      and 6.10 km are presented for a clear day with a medium high sun. The directional
      luminous reflectances of a variety of natural terrains and man-made surfaces
      measured under a clear sky with a moderately high sun are also presented. These
      data are applicable for use in visibility calculations and supplement the data
      presented in an earlier article [S. Q. Duntley, J. I. Gordon, John H. Taylor, C.
      T. White, A. R. Boileau, J. E. Tyler, R. W. Austin, and J. L. Harris, Appl. Opt.
      3, 549 (1964)].

PMID- 20048951
TI  - Atmospheric properties and reflectances of ocean water and other surfaces for a
      low sun.
AB  - Measurements of illuminance at sea level, directional luminous reflectances of
      ocean water and other surfaces, atmospheric beam transmittance, and path
      luminance for a day with an unobscured, low sun are presented. These data are
      applicable for visibility calculations for downward paths of sight.

PMID- 20048952
TI  - Optimum wavelength intervals for surface temperature radiometry.
AB  - Total reflectance measurements of some common surface minerals in the wavelength
      interval 0.5 micro to 23 micro show pronounced reflection maxima in some regions
      used for radiometric measurements of planetary surface temperatures. Variations
      in emissivity in the regions of such maxima could introduce significant errors
      into such temperature measurements. If measurements are restricted to the windows
      in the atmosphere of earth the 10-micro to 12-micro interval seems the best
      choice for radiometry since, in this interval, minerals are most uniformly black.

PMID- 20048953
TI  - [The optical beam].
AB  - The optical beam emitted by a high power laser has been studied. The beam cross
      section at various locations is considered, from optical and photometrical points
      of view. Output wavefront shaping is deduced as well as some ideas about focusing
      devices.

PMID- 20048954
TI  - Laser wavelength stabilization with a passive interferometer.
AB  - A control system has been devised for stabilizing the output wavelength of a
      laser by reference to an external passive optical element. This element,
      consisting of two spherical mirrors, forms an off-axis resonator that, when
      broadly illuminated by a laser beam, functions as a wavelength-sensitive
      discriminator. The stabilization control loop is closed by using a signal from
      this discriminator to tune the laser by moving one of its mirrors with a
      piezoelectric transducer. The error signal is proportional to changes in
      wavelength of the incident laser beam and is derived from the discriminator
      without deliberate frequency or amplitude modulation of the laser The optical
      arrangement does not return any light in the direction of the source and thus
      avoids wavelength pulling due to spurious reflections. Two independent helium
      neon lasers operating at 6328 A were stabilized against a common reference
      interferometer using this system. Their relative stability was studied by
      heterodyning the two outputs and analyzing the beat spectrum. Each feedback loop
      had a gain of 60 dB at dc falling off to 46 dB at 200 c/s and to 20 dB at 2
      kc/sec. The resulting wavelength stability was about Deltalambda/lambda = 2 x 10(
      10). The residual instability was mainly owing to room noise occurring at
      frequencies above the response of the feedback loops.

PMID- 20048955
TI  - Scanning active interferometer employing linear drive excitation and reflectance
      monitor.
AB  - A 0.93-m scanning active interferometer is described, and performance
      characteristics are discussed. An example of output signal both in the
      transmitted and reflected mode is given for passive and active operation.

PMID- 20048956
TI  - Chemical pumping through thermal decomposition of dimethyl peroxide.
AB  - A search for chemically pumped uv laser action in H(2)CO due to the thermal
      decomposition of CH(3)OOCH(3) is reported. Electrode ac discharge, and rf
      electrodeless discharge spectra of H(2)CO and CO augmented by chemical excitation
      via the reaction CH(3)OOCH(3) --> 2CH(3)O --> CH(3)OH + H(2)CO(*) are presented.
      The rate of production of excited state H(2)CO through thermal decomposition of
      CH(3)OOCH(3) is estimated by analysis of the kinetics of the reaction to be 2.3 x
      10(18) cm(-3) sec(-1). The population inversion DeltaF of H(2)CO required to
      produce stimulated emission in the 4231-A vibronic line is calculated to be 3 x
      10(14) cm(-3) as compared to an available DeltaF of 1.4 x 10(14) cm(Delta1). The
      possibility of using this thermal decomposition to produce excited collision
      partners for inducing laser action in other molecular or atomic species is
      discussed.

PMID- 20048957
TI  - Measurements of the airglow continuum with a birefringent filter photometer.
AB  - The airglow continuum in the immediate vicinity of the strong line emissions of
      the airglow is measured by introducing a second rotating polarizer to the
      birefringent filter. The results are compared with those obtained by other
      workers using different techniques. It is shown that the method would be useful
      for the study of the continuum in the immediate vicinity of the airglow.

PMID- 20048958
TI  - Particle sizing by means of the forward scattering lobe.
AB  - The angular distribution of scattered light in the main lobe of the Fraunhofer
      diffraction pattern of a particle changes rapidly with its size, but is largely
      independent of its refractive index. Even when the particle is so small (diameter
      less than a few wavelengths) that its forward lobe must be calculated from the
      Mie theory, the relative angular distribution within the central part is found to
      be given approximately by the Fraunhofer formula with obliquity factor, even for
      particles smaller than one wavelength, except near a minimum in the particle
      extinction efficiency factor calculated from the Mie theory. A measurement of the
      ratio between the scattered intensities at a pair of convenient angles within the
      lobe can thus give a useful estimate of the size of spherical and nonspherical
      particles without knowing their refractive index. The sizing error caused by the
      narrowing of the lobe near an extinction minimum is acceptable for many practical
      purposes, and can in any case be detected by comparing the size estimates derived
      from measurements at two different wavelengths. Families of curves for sizing by
      this simple procedure have been prepared. Sideways scattering instruments have
      been preferred hitherto because of their easier construction. A realization of
      their possibilities for sizing unknown particles should, however, stimulate the
      development of suitable forward scattering instruments.

PMID- 20048959
TI  - The history and current status of fourier transform spectroscopy.
AB  - This paper is concerned with the development of Fourier transform spectroscopy
      from its beginnings in Michelson's visibility technique through the present day
      application using modern digital computers. Methods used in maximizing the
      efficiency of the computation, as well as the interferometer, are discussed.
      Means of finding the Fourier transform other than by digital computer are
      mentioned, and currently available commercial instruments are named.

PMID- 20048960
TI  - New developments in multiplier phototubes for space research.
AB  - Recent developments in ruggedized high-performance multiplier phototubes are
      described for the uv and visible. The spectral radiant responses of photocathodes
      with peak quantum efficiencies up to 30% and higher are detailed over the
      applicable spectral regions. Photoemissive surfaces with two types of spectral
      responses are included: (a) spectrally selective cathodes of the extreme solar
      blind type for the far uv, and (b) cathodes with broad-band sensitivity over wide
      spectral ranges. The characteristics of dark current (dc and pulse counting),
      current amplification, equivalent noise input, and environmental conditions are
      reviewed for the various new tube types covered.

PMID- 20048961
TI  - On the preparation and properties of an optically isotropic polymer.
AB  - The preparation and properties of a highly cross-linked dibutyl phthalate
      modified methyl methacrylate polymer are described. The material is virtually
      optically isotropic with a refractive index near 1.5 and exhibits low absorption
      in the wavelength region 3000 A to 2 micro. It exhibits good dimensional
      stability when properly annealed and can be easily polished to close optical
      tolerances. It is unaffected by many organic and inorganic solvents. Careful
      preparation and annealing have removed gross density gradients and adventitious
      particle scattering in the medium.

PMID- 20048962
TI  - A universal tester.

PMID- 20048963
TI  - Aspheric mirrors by selective evaporation.

PMID- 20048964
TI  - Fabrication of high quality optical pinholes.

PMID- 20048965
TI  - Random error of interference fringe measurements using a Mach-Zehnder
      interferometer.

PMID- 20048966
TI  - Obtaining increased focal depth in bubble chamber photography by an application
      of the hologram principle.

PMID- 20048967
TI  - Comments on optical art.

PMID- 20048968
TI  - A few remarks regarding the calibration of the birefringent filter photometer.

PMID- 20048969
TI  - An image-forming slitless spectrometer for soft X-ray astronomy.

PMID- 20048970
TI  - Note on reflectance measurements on metals.

PMID- 20048971
TI  - Far infrared transmittance of irtrans 1 to 5 in the 250-10 cm(-1) spectral
      region.

PMID- 20048972
TI  - Humidity effects in the 8-13 micro infrared window.

PMID- 20048973
TI  - The effect of time Jitter in sampling of an interferogram.

PMID- 20048974
TI  - Bowl feed technique for producing supersmooth optical surfaces.

PMID- 20048975
TI  - Light beam scanning using conical refraction and optical activity.

PMID- 20048976
TI  - Perfect match in antireflection systems.

PMID- 20048977
TI  - Aerial photography of the earth's surface; its procurement and use.
AB  - Some of the most important applications of the optical sciences are in the taking
      of aerial photographs of the earth's surface and in the extraction of data from
      them. This article is intended to serve both as an introduction for the articles
      following it in this issue and as a summary of the factors that must be
      considered in the taking and interpretation of aerial photographs. Special
      emphasis is placed on the means by which photographic images of high quality can
      be obtained and viewed in order to facilitate the data extraction process A
      summary of the more important current applications of aerial photography in the
      earth sciences and life sciences also is provided.

PMID- 20048978
TI  - A spectrum matching technique for enhancing image contrast.
AB  - Interpretation of imagery requires contrast between the object being sought and
      its background. A technique is described for increasing the contrast of selected
      objects based on their spectral reflectance or emittance characteristics, and two
      applications are discussed. Means for implementing this technique with an optical
      mechanical scanner, multielement dispersing spectrometer, and electronic signal
      processing equipment are discussed.

PMID- 20048979
TI  - The remote surveillance of forest fires.
AB  - The radiometric considerations for fifteen forest fire surveillance and detection
      systems are reviewed. The system response is optimized in the 3-6-micro spectral
      region. A formulation of system noise-equivalent temperature is presented in
      terms of operational performance requirements and start-of-the-art component
      parameters. The radiometric criteria are investigated for detection of incipient
      forest fires and mapping of terrain background. Obscuration of fire targets by
      timber canopies is discussed. A prototype fire detection system based on these
      considerations is being evaluated.

PMID- 20048980
TI  - Effects of reflection properties of natural surfaces in aerial reconnaissance.
AB  - Measurements of the reflecting and polarizing properties of various soils, sands,
      and vegetation in the visible-and near-ir spectral regions show that dark
      surfaces polarize the reflected radiation strongly while highly reflecting
      surfaces have relatively weak polarizing properties. In general, the reflectance
      of mineral surfaces increases, and the degree of polarization of the reflected
      radiation decreases, with increasing wavelength and increasing angle of
      incidence. There is little or no indication of specular reflection from the
      surfaces for which measurements were made. Introduction of the reflection data
      into the equation of radiative transfer for clear and slightly turbid models of
      the earth's atmosphere shows that the upward radiation that would be incident on
      a high-altitude aircraft or satellite would be dominated by surface-reflected
      radiation for the red and near-ir regions over highly reflecting surfaces such as
      deserts, whereas atmospheric scattering is most important for short wavelengths
      and dark surfaces. Because of polarization effects, atmospheric transmission of
      optical contrasts is better in one orthogonal intensity component than the other,
      the difference being sufficient to merit polarizing optics in reconnaissance
      instrumentation under certain conditions.

PMID- 20048981
TI  - Overcast sky luminances and directional luminous reflectances of objects and
      backgrounds under overcast skies.
AB  - Two sky luminance distributions are given for overcast sky above snow-covered
      terrain, and directional luminous reflectance data are presented which were
      obtained under these skies. Luminous reflectances computed from Krinov spectral
      reflectance data for a variety of natural terrains measured under overcast are
      also included.

PMID- 20048983
TI  - Applied optics of optics and opticists.

PMID- 20048982
TI  - An equation for the local thermal emissivity at the vertex of a diffuse conical
      or V-groove cavity.
AB  - An exact, closed-form expression is derived for the apparent local emissivity of
      a point at the vertex of a diffuse conical or V-groove cavity. This expression is
      obtained by a substitution into an approximate equation for the apparent local
      emissivity of a point within a cavity of any shape. The exact expression depends
      only on the emissivity of the cavity wall material and the angle factor between
      the point at the cavity vertex and the cavity opening. The values predicted by
      this expression agree well with those obtained from a numerical solution of the
      integral equation characteristic of a diffuse conical cavity.

PMID- 20048984
TI  - Effective emissivity of a spherical cavity.
AB  - At the Istituto Termometrico Italiano a spherical cavity has been constructed as
      a radiation source in absolute temperature measurements. In theoretical
      prediction of its effective emissivity, a discrepancy appears between Gouffe's
      and DeVos's formulas. In this paper the authors discuss the approximations
      involved in DeVos's process and report corrections suitable to improve the
      precision of the results. With such corrections, computations based on both
      formulas agree within a wide variation range.

PMID- 20048985
TI  - Description of a Photoelectric Rotating Slit Elevation and Azimuth Sensor.
AB  - The Photoelectric Rotating Slit Elevation and Azimuth Sensor (PERSEAS) measures
      the azimuth and elevation of the line of sight to a target reflecting or emitting
      radiation in the 0.4- tol.1-micro portion of the spectrum. Angular field of view
      is 360 degrees in azimuth and 30 degrees in elevation. Eight stationary lenses
      are used with rotating fiber-optics slits and silicon photodiode detectors to
      produce electrical pulses which are time related to target angular coordinates.
      Data rate is one line-of-sight measurement per 2.5 msec. Accuracy is better than
      1 mrad.

PMID- 20048986
TI  - Effects of a simulated high-energy space environment on the ultraviolet
      transmittance of optical materials between 1050 A and 3000 A.
AB  - Transmittances of LiF, MgF(2), CaF(2), BaF(2), Al(2)O(3), and fused SiO(2)were
      measured from 1050 A to 3000 A before and after irradiation by 10(14)
      electrons/cm(2) first at 1.0 MeV and then at 2.0 MeV. Similar measurements were
      made with 10(14) electrons/cm(2) at 2.0 MeV using A1(2)O(3) to shield fused
      SiO(2), ADP, calcite, and Corning glass filters 9-54 and 7-54 from the direct
      electron beam. The electron energy and dose represent what one might expect to
      encounter in the artificial radiation belt after one year in a circular, near
      polar orbit at 1400 km. From these measurements it is concluded MgF(2), BaF(2),
      and A1(2)O(3) have the greatest potential for space applications in the uv.

PMID- 20048987
TI  - Optical properties and applications of photochromic glass.
AB  - Corning Glass Works has recently developed a series of inorganic bulk
      photochromic materials. The present paper is concerned with the results of an
      extensive laboratory investigation of their properties. It is shown that the
      fatigueless reversibility and the optical characteristics of these glasses hold
      definite. promise for several applications.

PMID- 20048988
TI  - The measurement of homogeneity of optical materials in the visible and near
      infrared.
AB  - A procedure is described for determining the inhomogeneities of a sample of
      optical material in terms of small changes in index of refraction at discrete
      points over the measured surface. The method is used in the visible- and near-ir
      regions of the spectrum. An He-Ne gas laser source was used for the ir
      measurements. The variation in index was mapped with contour lines enclosing
      areas of similar index variations. The largest index change in 1-cm distance was
      noted and recorded as the maximum variation per centimeter. Over twenty-five
      different samples of six different materials were examined. The results are
      presented in a chart indicating the range of maximum refractive index variations
      of the samples observed. Data are shown to illustrate the possibility of
      determining index values to higher precision than the material justifies.

PMID- 20048989
TI  - Complex spatial filtering with binary masks.
AB  - Usually a hologram is produced by means of an interference experiment. Here,
      however, we let a computer- guided plotter draw the hologram. The plot, which has
      to be minified and recorded on film, contains no grey, only binary transmittance
      values. Our binary holograms yield reconstructed images of a quality equal to
      that of images obtained from usual holograms of comparable dimensions. When a
      Fourier hologram is inserted into the Fraunhofer plane of a coherent image
      forming system, it acts as a special type of a spatial filter, a so-called
      optical matched filter. Our binary matched filter is suitable for optical
      character recognition, the same as the usual optical matched filter introduced by
      Vander Lugt.

PMID- 20048990
TI  - OSA Research and Education.

PMID- 20048991
TI  - Interference filters for the far ultraviolet (1700 A to 2400 A).
AB  - The transmission characteristics of Fabry-Perot type aluminum-magnesium fluoride
      aluminum interference filters for the wavelength region 1700 A to 2400 A are
      described. Typical peak transmissions of 0.25 with bandpasses <300 A are obtained
      with first-order filters on fused silica substrates. Secondorder filters give
      narrower bandpasses. Methods of filter preparation are described briefly, and the
      effects of the optical properties of the aluminum reflecting layers on filter
      performance are discussed.

PMID- 20048992
TI  - Backward wave optical amplification by an asymmetric active interference filter.
AB  - Equations are given for reflectance, bandwidth and root gain-bandwidth of an
      active interference filter having unequal mirror reflectances and operating in
      the reflecting mode. Gain for various configurations is compared keeping the
      product of the mirror reflectances constant. It is shown that the reflectance
      gain of an asymmetric configuration can be greater than the transmittance gain
      while the bandwidths are identical. Specific examples are treated to show how
      device gain depends on single-pass gain and input and output mirror reflectances.

PMID- 20048993
TI  - Interferometry through the turbulent atmosphere at an optical path difference of
      354 m.
AB  - A modified Michelson interferometer with a stable He-Ne laser source has been
      used to study fluctuations in the mean refractive index over a long path through
      the turbulent atmosphere. Distinct interference fringes were obtained at mirror
      separations up to 177 m, corresponding to an optical path difference of 354 m.
      The spatial stability of the interference fringes was found to decrease with
      increasing optical path length, indicating an increasing contribution from the
      atmosphere. Details of the interferometer and the experimental procedure are
      given as well as a discussion of the fluctuations in the mean refractive index.

PMID- 20048994
TI  - Interferometry and laser control with solid Fabry-Perot etalons.
AB  - The use and analysis of solid Fabry-Perot etalons for interferometry and laser
      control are discussed and supported with experimental data. Low angle scattering
      is found to be an important factor influencing finesse and peak transmission.
      Thermal tuning sensitivity and wedge-angle control with thermal gradients are
      analyzed and illustrated. Control of laser oscillations using a solid-state
      etalon as a laser cavity end mirror is discussed. The use of the solid etalon as
      an optical cavity coupler is applied to the problem. of sideband energy removal
      from an internally modulated laser.

PMID- 20048995
TI  - A sun-pumped cw one-watt laser.
AB  - 1 W of w laser output has been obtained at room temperature from a sun-pumped,
      neodymium-doped YAG crystal. The water-cooled laser rod was pumped with a
      modified Cassegrain sun-tracking telescope consisting of a 61-cm diam
      paraboloidal primary mirror collector, a water-cooled hyperbolic-cylindric
      secondary mirror and a hemicircular cylindric tertiary mirror. The cylindrical
      image volume was coincident with 24 mm of the 3-mm by 30-mm YAG rod. The spike
      free output was obtained for hours at a time with a late October sun at a 42
      degrees North latitude. Using the same primary mirror and near-unity numerical
      aperture refractors, approximately 1.25 W were obtained in 7 msec pulses from an
      uncooled, sun-pumped, neodymium-doped, glass rod. Further refinements in the
      telescope and the laser crystal, and a space environment, should allow 1 W of
      laser output to be generated by using a 30-cm diam collector.

PMID- 20048996
TI  - Laser mode control by internal modulation using the transverse electrooptic
      effect in quartz.
AB  - A practical method is described for inducing fm and phase-locked oscillations in
      a small He-Ne laser at 6328 A, with negligible reduction of output power.
      Internal phase modulation was produced using the electrooptic effect in synthetic
      crystal quartz. Although crystal quartz has a small electrooptic effect, it has
      nearly ideal optical properties, and excellent optical surfaces can be produced
      on it; thus, the laser power is not reduced significantly when the modulator
      crystal is inserted. The laser spectrum and rf mode beats were observed at
      several modulation frequencies, and suppression of low-frequency amplitude
      modulation on the output was obtained with stable fm or phase-locked operation.
      Agreement with the Harris and McDuff fm theory is discussed.

PMID- 20048997
TI  - [Laser emission].
AB  - In solid-state laser emission, the spectral width mainly depends on two factors:
      frequency shift and broadening due to the short duration of the spikes. The
      latter being more important as the emitted wave train is shorter and the envelope
      slope steeper, it is of interest to consider an O-switched laser. The importance
      of the frequency shift compared to spectral width is determined for single pulses
      by measuring variations of the emitted wavelength as a function of time.
      Experiments are carried out by using a high-speed rotating mirror camera. The
      time resolution is about 3.2 nsec. Some results are reported, deduced from streak
      photographs of Fabry-Perot rings. For a particular mode, a wavelength shift of
      the order of 3 x 10(-3) A in 50 nsec was detected; this shift is not a linear
      function of time.

PMID- 20048998
TI  - Shearing interferometers for testing corner cubes and right angle prisms.
AB  - A wavefront reversing interferometer and an inverting interferometer are
      described for use in testing corner cubes and right angle prisms. Both the
      interferometers are stable, easy to adjust, and require comparatively simple
      setup. They have adequate sensitivity for measuring the divergence of the
      reflected wavefronts, but do not give directly the symmetrical errors of the
      prisms. With the inverting interferometer, the latter can be determined by
      changing the shear. Methods are suggested for testing the prisms during
      manufacture and correcting their defects by use of these interferometers.

PMID- 20049000
TI  - Physics Today.

PMID- 20048999
TI  - A simple ac photometric method for measuring complex Kerr Magnetooptic
      coefficients.
AB  - A method is described for measuring the amplitude and phase of the complex Kerr
      magnetooptic coefficients. A magnetic metal surface to be measured is switched
      between its magnetic states at an ac rate, thereby modulating a reflected light
      beam. By measuring the modulation depth with a synchronous detector and one
      angle, the two quantities above are determined. The method requires no precision
      optical equipment as is needed with polarimetric techniques.

PMID- 20049001
TI  - Optical activities in industry.

PMID- 20049002
TI  - A computer designed lens by a nonexpert.
AB  - This paper describes the approach used by a nonexpert to design a lens by using
      the LASL lens design code for an IBM 7094 computer. The example lens, the
      author's first attempt at lens designing, is to be used as an objective in a high
      speed rotating-mirror smear camera.

PMID- 20049003
TI  - Rays and ray envelopes within stable optical resonators containing focusing
      media.
AB  - In stable resonators any given initially paraxial rays remain close to the axis
      of the structure and are, in fact, confined within well-defined contours-the
      envelope of the ray system. Previously, envelopes of rays in empty resonators had
      been found and their form identified with the variation of the spot size. This
      geometric optical approach is extended to general resonators, comprising
      arbitrary arrangements of lenses and convergent or divergent inhomogeneous
      focusing media. An invariant quadratic form involving parameters descriptive of
      any of the ray segments that result from a given initial ray segment leads to a
      differential equation satisfied by the ray segments and their envelope in
      portions of the resonator. A maximum-minimum problem for the envelope is
      formulated and solved. In convergent media the envelope function is found to be
      periodically modulated. The period of the modulation depends only on the
      properties of the convergent medium; the location of relative maxima and minima,
      as well as their ratio, depends on both the medium and associated optics. In
      special cases, results are compared with available solutions of the corresponding
      electromagnetic problem. A particularly simple resonator is analyzed, and
      envelope characteristics correlated with the stability limits.

PMID- 20049004
TI  - Ionic polishing of optical surfaces.
AB  - The controlled removal of material from the surface of insulators has been
      observed by using a positive ion beam. In the energy range 0.5-2.0 MeV the
      sputtering yield was observed to be unity. The application of this technique to
      the manufacture of high quality optical surfaces is discussed.

PMID- 20049005
TI  - Integrating sphere for the infrared.
AB  - An integrating sphere of simple construction has been developed for the ir. It
      has a high efficiency that is not materially affected by aging processes.
      Experimental measurements of the relative efficiency of this sphere have been
      made for the wavelength range from 1 micro to 2.6 micro. These data agree with
      theoretical predictions. It was also predicted that the efficiency of the sphere
      would increase from 2 micro through to the millimeter wavelength range. The
      measurements show the ir sphere to have a higher efficiency (2.5 times higher at
      2.6 micro) than the conventional MgO-coated integrating sphere.

PMID- 20049006
TI  - Spectral analysis using the electronic scanning spectrometer.
AB  - Spectral scanning is accomplished in an electronic scanning spectrometer by means
      of a television-type camera tube called an image dissector. Since the scanning is
      done electronically, extremely rapid spectral scanning can be performed without
      any mechanical movement. The standard instrument has selectable scan rates of 100
      or 1000 spectral scans per second, although faster and slower scan rates are
      possible. The sensitivity of the spectrometer is the same as a conventional
      mechanical scanning spectrometer using a photomultiplier detector if it were
      possible to scan the latter at the same high rate. The instrument is being used
      to investigate the time variation in spectral output of light sources, but should
      also be useful in other studies such as explosions, shock tubes, lightning,
      plasmas, missile launch and reentry, and other sources of intense transitory
      radiation phenomena.

PMID- 20049007
TI  - Optical activities in the universities.

PMID- 20049008
TI  - Generalization of Seidel astigmatism and Petzval curvature.
AB  - In a paper probably to be published in Optika i Spektroskopiya the wave
      aberration for sagittal focus for the arbitrary surface of rotational symmetry
      has been carried out on the base of the astigmatic beam invariant D(s) =
      nu(s)d(s). The resulting expression for the wave aberration has been reformulated
      into three terms which, in the Seidel region, go over into astigmatism (the
      first) and into the Petzval curvature (the second) while the third disappears.

PMID- 20049009
TI  - Focal properties of a plane grating in a convergent beam.
AB  - Focusing from a plane grating can be accomplished by using convergent radiation
      incident on the grating in such a manner that any incident angle alpha(n), the
      resulting diffraction angle beta(n), will be on the same side of the grating
      normal. The theory for the focal properties is developed by applying Fermat's
      principle of least time to selected terms resulting from a finite series
      expansion of the system's distance function. Derivations are given for finding
      the focal curve equation, astigmatism, and coma, of the most usable configuration
      of the optical components. Discussions of the aberrations disclose methods for
      eliminating the astigmatism and reducing the coma.

PMID- 20049010
TI  - Application of the Abel integral equation to spectrographic data.
AB  - An improved method is proposed for applying the Abel integral equation to
      radiance data gathered from rotationally symmetric sources by side-on
      observation. The method involves dividing the data into a number of segments
      going out from the center. A least-squares polynomial is then fitted to each
      segment so that the inverted Abel integral equation can be integrated exactly to
      yield the emission coefficient. It is shown, with test curves approximating
      spectral line shapes from nonhomogeneous sources, that the method becomes
      superior to the other more common numerical methods of reducing such data as the
      number of data points becomes large. This superiority increases as the data
      scatter increases.

PMID- 20049011
TI  - Intensity measurements in ultramicroscopic studies.
AB  - A method is described that permits the quantitative measurement of light
      scattered by the bulk material and individual scattering centers in transparent
      crystals and photographic recording with an ultramicroscope. The bulk scattering
      observed in sodium chloride single crystals is proved to be Brillouin scattering.
      This suggests the use of Brillouin scattering as a reference for the measurement
      of the intensity of light scattered by individual centers.

PMID- 20049012
TI  - Stimulated effects in N(2) and CH(4) gases.
AB  - Stimulated Brillouin scattering from N(2) and CH(4) using a giant-pulse laser has
      been observed in an arrangement whereby the laser cannot relase and amplify the
      back-scattered radiation. This allows a quantitative study of the parameters
      affecting stimulated Brillouin scattering. The back-scattered beam converges at
      the same angle at which the laser beam diverges. The Brillouin component can have
      a narrow spectral width, one-third that of the laser itself, and in some cases
      can have a duration of only a few nanoseconds. N(2) at high pressure can back
      scatter as much as 45% of the incident power. The speeds of sound in CH(4) and
      N(2) have been measured at lower pressures than were previously reported.

PMID- 20049013
TI  - Integrated intensity of the 6.3-micro band of water vapor.
AB  - A curve of growth method was used to measure the integrated intensity of the 1(
      1)-1(1) rotational line of the nu(2) fundamental band of H(2)O. All measurements
      were taken at a temperature of 523 degrees K, with pressures varying between 0.2
      5 atm. By neglecting vibration-rotation interaction, the total band intensity was
      derived for which a value of S(band) = 220 +/- 22 cm(-2) atm(-1) at NPT was
      found.

PMID- 20049014
TI  - Dynamic orientation of spin I nuclei. II.
AB  - The Jeffries-Abragam effect in an electron-nuclear coupled spin system (S =
      (1/2), I = 1) is studied in detail. From a population-distribution analysis of
      the system, the nuclear orientation parameters are computed and their temperature
      dependence discussed. Conditions for obtaining stimulated emission are examined
      in detail. The results are compared with those of an earlier paper.

PMID- 20049015
TI  - Diffraction by apertures of wavelength dimensions.

PMID- 20049016
TI  - Far infrared transmission through metal light pipes with low thermal conductance.

PMID- 20049017
TI  - Mirror misalignment in fourier spectroscopy using a michelson interferometer with
      circular aperture.

PMID- 20049018
TI  - Recent advances in multicolor wavefront reconstruction.

PMID- 20049019
TI  - On some properties of photographically produced diffraction gratings.

PMID- 20049020
TI  - Transform relations in coherent systems.

PMID- 20049021
TI  - Image orthicon video fall-off.

PMID- 20049022
TI  - Oscillation conditions for superradiant and feed back amplifier lasers.

PMID- 20049023
TI  - Polarization sensitivity of the RCA 6903 photocathode tube.

PMID- 20049024
TI  - Optical methods of molecular spectroscopy.
AB  - A survey is presented of current trends in molecular spectroscopy research using
      optical methods. The scientific interests of workers in this field and areas of
      currently active research are reviewed.

PMID- 20049025
TI  - The Optical Society.

PMID- 20049026
TI  - Kinetic spectroscopy in the infrared: a rapid-scan infrared spectrometer.
AB  - A description is given of an ir spectrometer capable of scanning the region 2-15
      micro in 10 microsec at a repetition rate of 20,000 scans/sec. The application of
      the instrument to problems in kinetic spectroscopy is demonstrated by the flash
      photolysis of CF(3)I: Ar mixtures and the subsequent detection of transient
      absorption at 1250 cm(-1) due to the gaseous CF(3) radical.

PMID- 20049027
TI  - Optical activities in industry.

PMID- 20049028
TI  - A dual recording, variable range, rapid-scan spectrometer; comparison of
      simultaneously recorded stark-broadened Halpha and Hbeta line profiles.
AB  - An ultrarapid scanning spectrometer has been constructed that records spectra at
      a constant angle of diffraction. The spectral scanning is accomplished by the
      rotation of a high-speed rotating mirror (7.6 cm diam) that causes a collimated
      light beam to sweep across a plane grating, changing the angle of incidence. The
      full-aperture scanning range depends upon the over-all grating width, upon the
      grating spacing, and upon the orientation of the grating with respect to the high
      speed mirror. For example, a 12.5-cm, 1200-lines/mm grating gives a scanning
      range of approximately 2000 A on each of two separate detector systems, or a
      total range of 4000 A that can be centered at any wavelength between 4000 A and
      8000 A. This grating provides a theoretical resolving power of approximately
      85,000 in the first order, a reciprocal dispersion of 17.5 A/mm at f/5, and a
      spectral scan speed of 115 A/microsec at 1100 rps. This spectrometer has been
      used to record, simultaneously, Stark-broadened Halpha and Hbeta emission line
      profiles from a transient plasma generated in the impulse tube. Electron
      densities calculated from the half-width of the Hbeta profiles are in good
      agreement with values obtained by fitting the line wings of the self-absorbed
      Halpha profiles to the theoretical profiles of Griem, Kolb, and Shen.

PMID- 20049029
TI  - Double beam spectrophotometry in the far ultraviolet. 1: 1150 A to 3600 A.
AB  - The instrument described is a double beam spectrophotometer with a wavelength
      range of 1150 A to 3600 A. Continua are supplied by three microwave-excited, rare
      gas discharge lamps and a standard hydrogen lamp. A 1-m, normal-incidence,
      concave-grating monochromator is used. The beam splitting arrangement is an
      oscillating toroidal mirror, resonant at 11.3 c/s and arranged so that only a
      single reflection in each beam is required. The detectors are type EMI 6255S,
      each with a sodium salicylate phosphor. A ratio recording measuring system is
      used, with absorbance indicated on a 1.5-cycle logarithmic recorder. The
      performance data include vapor absorption spectra of several organic compounds
      and spectral reflectance measurements of magnesium-fluoride-coated aluminum
      surfaces. Stray light measurements are made by considering the constancy of
      absorbance vs pressure of water vapor at several wavelengths.

PMID- 20049031
TI  - Applied optics of optics and opticists.

PMID- 20049030
TI  - An order sorter for high resolution spectrographs.
AB  - A simple, but versatile, order sorter for use with stigmatic plane grating
      spectrographs is described. The optical components can be interchanged easily to
      obtain the required separation between the orders. The properties of the
      dispersing materials are discussed, and a method for adjusting the order sorter
      is described.

PMID- 20049032
TI  - Astigmatism compensation in the Czerny-turner spectrometer.
AB  - By distorting the plane grating into a concave cylinder, astigmatism found
      normally in the Czerny-Turner spectrometer can effectively be eliminated. The
      level of distortion would require metal grating blanks to avoid shearing
      stresses. The stigmatic principle has recently been demonstrated on a low
      resolution, uv illuminator patterned after the Czerny-Turner spectrograph. For
      the illuminator, it was desired that the image integrity of the circular entrance
      aperture be maintained at the focal plane. There is good reason to believe that
      medium resolution (approximately 1 A) instruments employing this stigmatic
      principle would maintain their resolution.

PMID- 20049033
TI  - Standardization of fluorescence spectra and the calibration of
      spectrofluorimeters.
AB  - A technique is proposed that can be used to calibrate the amplitude of
      fluorescence spectra so that spectra reported by different laboratories can be
      compared quantitatively. The technique is based upon the scattering of light by a
      solution of polystyrene. In order to compare quantitatively data obtained from
      different spectrofluorimeters, these terms are defined: the spectrofluorimetric
      sensitivity, the noise-equivalent concentration, and the fluorophotometric
      reproducibility. The author shows how these quantities can be measured with the
      polystyrene standard.

PMID- 20049034
TI  - Drum dispersion equation for Littrow-type prism spectrometers.
AB  - A simple analytic procedure has been developed for calibrating the wavelength
      drum of a Littrow-type prism spectrometer. Only three measured drum readings are
      required to specify the drum calibration over a broad wavelength range (uv to ir)
      with an accuracy of the order of the instrumental accuracy. This procedure can be
      applied to different prism materials for which measurements of refractive index
      have been performed. It is based on an approximate expression, derived from
      geometrical optics, relating the drum reading D(lambda) to the calculated
      refractive index n(lambda): D= A - B(a(2) - n(2))((1/2)). The index n(lambda) is
      calculated from the appropriate parametric equation. The temperature for the
      n(lambda) values need not be exactly that of the prism temperature during
      measurements. This expression was investigated for wavelengths in the range 0.3
      micro to 2.25 micro using a sodium chloride prism. Computed drum positions D
      agreed with measured drum positions to within experimental error. Unknown
      wavelengths were computed from their measured drum positions to within the
      accuracy of the measurements.

PMID- 20049035
TI  - The circularly symmetric grille spectrometer.
AB  - A grille spectrometer, with grilles formed of alternately transparent and
      nontransparent concentric circular zones, has been constructed. The quantity of
      light that can be accepted from an extended source with such an instrument is
      orders of magnitude greater than that of a slit spectrometer with the same
      resolution, and greater even than that of a scanning Fabry-Perot spectrometer of
      the same resolution. For extended sources of brightness insufficient to bring the
      photon shot noise above detector noise, the grille spectrometer offers an
      advantage over the slit spectrometer and Fabry-Perot in greater signal to noise.
      In cases where the photon shot noise is greater than the detector noise, the
      better signal to noise applied for emission-line sources, and also for continuum
      sources if a large interference filter premonochromator is used. The spectrometer
      is being used in airglow observation.

PMID- 20049036
TI  - A high-resolution, far infrared double-beam lamellar grating interferometer.
AB  - A high-resolution, far ir lamellar grating interferometer that operates in either
      a single-beam or a double-beam differencing mode of operation is described. The
      instrument covers a frequency range of 10 cm(-1) to 125 cm(-1) (1000 micro to 80
      micro). To illustrate the general performance of the instrument the pure
      rotational spectrum of water vapor between 15 cm(-1) and 115 cm(-1) is presented.
      It is estimated that the absorption line centers of strong isolated lines are
      measured to within +/-0.008 cm(-1). To illustrate the resolution of the
      instrument, low wavenumber portions of the pure rotational spectrum of DCl are
      shown. The Cl(35)-Cl(37) isotope splitting of the J = 2 --> 3 transition (32.3
      cm(-1)) is clearly resolved. The calculated separation of these two lines is
      0.094 cm(-1).

PMID- 20049037
TI  - A far infrared interferometric spectrometer with a special electronic computer.
AB  - A far ir interferometric spectrometer with a special electronic computer has been
      constructed. The interferometer is of the conventional Michelson type. The
      electronic computer, which consists of an analog computer to introduce
      apodization and a digital computer to calculate the Fourier cosine transform, is
      fed with the detector output of the interferometer and is operated by electric
      pulses from a moire fringe counter that is part of the mechanism that measures
      the path difference in the interferometer. The digital computer makes the
      calculation in parallel for each of one thousand spectral positions during the
      scanning of the interferogram. It takes 0.45 sec for the calculation at each path
      difference. A spectrogram can be obtained in 10 min; this includes calculations
      at one thousand path differences and 2 min for recording. During the scanning,
      values stored in the memory corresponding to the one thousand spectral positions
      can be displayed on a synchroscope in order to provide a spectrogram that is low
      in resolving power at the beginning and high at the end of the scan. Some results
      obtained with water vapor absorption are shown.

PMID- 20049038
TI  - Real-time spectral synthesis in Fourier spectroscopy.
AB  - A real-time technique to synthesize the spectral distribution from the
      corresponding interferogram is described. A portable real-time synthesizer has
      been constructed and test results are presented. Functions with known spectra and
      an actual interferogram have been used for purposes of evaluation.

PMID- 20049039
TI  - Solid state studies by means of Fourier transform spectroscopy.
AB  - A commercially available Michelson interferometer has been adapted to meet the
      needs of our research. Transmission and reflection measurements of solid state
      materials can be made over the wavelength range of 25-1000 micro (400-10 cm(-1)).
      Provision has been made for the samples in each case to be studied from 4 degrees
      K to 700 degrees K with suitable cryostats and heated sample holders. These
      devices can easily be interchanged in the interferometer and also in a single
      beam far ir vacuum gratings pectrometer so that the measurements can be
      duplicated when necessary, using conventional spectroscopic techniques. The
      interferometer has the unique advantage of covering a broad frequency range
      without changing the operating conditions. A suitable choice of beam splitter
      thickness and ionic crystal powder filter combinations provides maximum
      efficiency in the area of interest. The region beyond 250 micro shows a rapid
      deterioration in signal to noise, and the relative merits of various cooled
      detectors and the Golay detector have been studied. Polarization measurements on
      solids have also been of interest, and various polarizers have been investigated.
      Applications of interferometry applied to a number of solid state problems are
      described. These include the dielectric dispersion in perovskites, compound
      semiconductors, internal molecular and lattice vibrations in inorganic materials
      and other related compounds. The relative advantages of single-sided vs double
      sided interferograms in terms of accurate intensity measurements are compared.
      Examples of each are discussed.

PMID- 20049040
TI  - Transfer efficiency formula for diffusely reflecting laser pumping cavities.
AB  - A method is presented for estimating the transfer efficiency of laser pumping
      cavities that have diffusely reflecting walls. The method is based on the
      assumption that the light inside the cavity is approximately isotropic. It is
      demonstrated that such a simplification leads to estimates of transfer efficiency
      that agree well with estimates obtained by Monte Carlo methods. Curves are given
      for the proportion of isotropic light absorbed by a cylindrical absorbing crystal
      as a function of the product of radius and absorption coefficient. This
      proportion is an important parameter in the transfer efficiency estimation.

PMID- 20049041
TI  - Faraday rotators for high power laser cavities.
AB  - The large values of Faraday rotation obtained with the use of pulsed high field
      magnets are shown to be applicable to the control of laser cavities. Experiments
      are described in which high-field magnets are operated up to 400 kOe in order to
      introduce large rotations in short, highly transparent optical media. With a ruby
      laser, interesting pulse enhancement and periodic equispaced output is observed
      and related to the switching rate of the field, typically 20 kOe/micro sec. Used
      with a cryptocyanine shutter, it is found that either a single giant pulse or a
      well-spaced series of pulses can be obtained. These are synchronized with respect
      to the varying magnetic field with fractional microsecond accuracy.

PMID- 20049042
TI  - A simple polarization calibrator.
AB  - The theory, design, and performance of a simple polarization calibrator based
      upon the polarization of specularly reflected light are presented and discussed.
      A formula is derived for the Rubenson degree of polarization of specularly
      reflected light in terms of the angle of incidence and the refractive index
      (real) of the material of the reflector. Criteria are presented for the design of
      an optimal diaphragm to minimize the depolarizing effects of light that has
      undergone a single internal reflection inside the body of the reflector.

PMID- 20049045
TI  - Wavefronts and construction tolerances for a cat's-eye retroreflector.
AB  - A retroreflector (a device that reflects an incident beam of light through
      exactly 180 degrees ) constructed from a primary concave mirror and a small
      secondary mirror near its paraxial focus, the so-called cat's-eye retroreflector,
      has been investigated. Ray-tracing of systems with both spherical and parabolic
      primaries suggests that the latter are considerably superior to the former and
      comparable to a cube-corner retroreflector. The investigation has also enabled
      mechanical tolerances for the construction of a cat's-eye retroreflector to be
      deduced. The predicted tolerances may be much easier to attain than those for a
      cube-corner retroreflector.

PMID- 20049046
TI  - Simplification of holographic procedures.
AB  - The present state of the holographic art has set many stringent parameters on the
      production of holograms, such as extreme mechanical, temperature, and air
      stability for long periods of time, and slow film emulsions with extremely high
      resolution. The Physical Sciences Laboratory of the U.S. Naval Training Device
      Center has investigated, experimented, and produced many clear high resolution
      holograms in a ground-level Butler Building without close temperature controls
      and using other than expensive, massive, and extremely rigid optical mounts and
      equipment.

PMID- 20049047
TI  - Optical hole sensing using fiber optics.
AB  - An important application of fiber optics to data processing is to illuminate hole
      positions of punched-card reading-stations. In the IBM 59 Card Verifier, flexible
      incoherently oriented bundles are employed to provide a reliable, efficient, and
      practical method of sensing holes in punched cards. A phototransistor detects the
      light coming through open holes and then operates a reed relay directly. In
      addition, a mechanical light chopper also uses fiber optical components to
      provide light pulses for the electronic clock to time the machine. An electronic
      circuit is used to latch reed relays so that the useful signal is digital, rather
      than the analog hole-to-no-hole light ratio.

PMID- 20049048
TI  - Lens designs for a 2032-mm f/8 doublet achromat.
AB  - A lens to be used in photographing the sun's corona in monochromatic light was
      developed from an existing Fraunhofer design. Measured performance of the
      constructed lens exceeded predictions. The original lens design was evaluated and
      modifications prescribed by machine analysis with the LASL program, which makes a
      statistical analysis of the traced skew rays that generate the geometrical image
      spots.

PMID- 20049049
TI  - Rotating prism design for continuous image compensation cameras.
AB  - The rotating prisms used in high-speed motion-picture cameras have been designed
      empirically since their first use thirty-two years ago. During that period, there
      have been advances made in glass technology and fabrication which have resulted
      in the production of better images. This paper summarizes the latest state of the
      art wherein it is demonstrated that prism design should not be confined to the D
      line of the spectrum, but expanded to cover the uv and ir portions of the
      spectrum. The prism design shall cover: (1) selection of the average angle of
      incidence for exposure; (2) the choice of glass or other transparent media; (3)
      the correlationship between image and film velocity; and (4) discussion of the
      inherent aberrations, namely, nonlinear distortion, sagittal and tangential coma,
      prismatic astigmatism, change in back focus due to prism rotation; (5) shuttering
      action; and (6) aperture design. There have only been fragmentary data published
      on the subject to date. It is necessary to secure this thirty years' experience
      before this datum is forever lost. Recommendation for future action is made,
      including computer studies for optimization of design.

PMID- 20049050
TI  - Pinhole array camera for integrated circuits.
AB  - A pinhole camera has been designed, fabricated, and tested for the production of
      multiple images for integrated circuits, consisting of an array of precisely
      positioned, uniform diameter pinholes and a vacuum back to hold the film or
      plate. This camera was designed to replace the step-and-repeat camera method that
      is presently used for producing multiple images. The two basic requirements for
      repetition of circuit patterns are the achievement of high image quality and
      precise registration between all the masks in a set. The arrangement discussed
      here permits lines of 12.5 microm width in the final working mask with precise
      registration to all other masks in the set.

PMID- 20049051
TI  - The ray packet equivalent of a Gaussian light beam.
AB  - A packet of light rays is defined that is equivalent to a Gaussian beam of light.
      The transformation of the Gaussian beam as it passes through any combination of
      perfect lenses and flat dielectric interfaces can be found by applying geometric
      optics to the equivalent ray packet.. The envelope of the ray packet gives the
      Gaussian beam spot size and the curves perpendicular to the average ray slope
      give the Gaussian beam phase fronts.

PMID- 20049052
TI  - An air driven light modulator.

PMID- 20049054
TI  - The rosette--a unipoint multiple internal reflection element.

PMID- 20049053
TI  - A vacuum-tight infrared cell for reactive liquids.

PMID- 20049055
TI  - Demonstration of the application of wavefront reconstruction to interferometry.

PMID- 20049056
TI  - Effect of high-velocity mirror translation on optical coherence in laser
      interferometers.

PMID- 20049058
TI  - Comment on the effect of trapped light on the output of a ruby laser.

PMID- 20049057
TI  - Argon bomb pumping of ruby laser.

PMID- 20049059
TI  - Determination of small wedge-angles using a gas laser.

PMID- 20049060
TI  - Third-order wavefronts and related null tests.

PMID- 20049062
TI  - Rapid determination of radiant flux distribution with photochromic films.

PMID- 20049061
TI  - Faraday effect measurements with pulsed magnetic fields.

PMID- 20049063
TI  - A technique for optically convolving two functions.

PMID- 20049064
TI  - Carboxylic Acid to Thioamide Hydrogen Bonding.
AB  - The lactam groups of dipyrrinones avidly engage in amide-amide hydrogen bonding
      to form dimeric association complexes in nonpolar solvents (in CHCl(3), K(D)
      ~25,000 M(-1) at 22 degrees C). The corresponding thioamides (dipyrrinthiones),
      prepared from dipyrrinones by reaction with Lawesson's reagent, also form
      intermolecularly hydrogen-bonded dimers in nonpolar solvents, albeit with much
      weaker association constants (in CHCl(3), K(D) ~200 M(-1) at 22 degrees C). When
      a carboxylic acid group is tethered to C(9) of the dipyrrinone, as in the
      hexanoic acid of [6]-semirubin, tight intramolecular hydrogen bonding between the
      carboxylic acid group and the lactam moiety (intramolecular K(assoc) >>25,000) is
      found in CHCl(3) with no evidence of dimers. In contrast, the analogous
      dipyrrinthione, [6]-thiosemirubin, eschews intramolecular hydrogen bonds, as
      determined using NMR spectroscopy and vapor pressure osmometry, preferring to
      form intermolecularly hydrogen-bonded dimers of the thioamide-thioamide type.

PMID- 20049065
TI  - S-Methylidene Agents: Preparation of Chiral Non-Racemic Heterocycles.
AB  - Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords
      the desired three-membered heterocycle in excellent yield. The sulfur ylide is
      generated in situ upon decarboxylation of carboxymethylsulfonium betaine
      functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed,
      the highest level of conversion of pi-acceptor to heterocycle was obtained having
      S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene
      aziridinations and epoxidations involving the decarboxylation of
      carboxymethylsulfonium betaine functionality complements existing technologies
      with the advantages of the reaction protocol, levels of conversion and scope.
      While moderate levels of diastereocontrol were observed in the aziridination of
      imine functionality, the four oxiranes resolved using Jacobsen's Co(II)-salen
      complex were obtained in both high yield and enantioselectivity. The isolated
      chiral non-racemic oxiranes constitute the formal synthesis of chelonin-B and
      combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5
      trimethoxybenzaldehyde respectively.

PMID- 20049068
TI  - Quality management and safety culture in medicine - Do standard quality reports
      provide insights into the human factor of patient safety?
AB  - In 1999 the Institute of Medicine (IOM) published the landmark report "To err is
      human: building a safer healthcare system" highlighting critical deficiencies
      within the area of patient safety. As a consequence, safety culture evolved as a
      core component of quality management in medicine. Purpose of the investigation at
      hand was to find out to what extent this is reflected in standard quality reports
      issued by German hospitals providing maximum medical care. Reports issued for the
      year 2006 were analysed with respect to the appearance of indicators for the
      presence of a safety culture. Results suggest that despite the huge awareness for
      patient safety caused by the IOM report, the topic of safety culture does not get
      the anticipated attention within the quality reports. This may indicate that the
      current requirements for the quality reports do not facilitate transparency when
      it comes to the human factor of patient safety.

PMID- 20049067
TI  - Water, electrolytes, vitamins and trace elements - Guidelines on Parenteral
      Nutrition, Chapter 7.
AB  - A close cooperation between medical teams is necessary when calculating the fluid
      intake of parenterally fed patients. Fluids supplied parenterally, orally and
      enterally, other infusions, and additional fluid losses (e.g. diarrhea) must be
      considered. Targeted diagnostic monitoring (volume status) is required in
      patients with disturbed water or electrolyte balance. Fluid requirements of
      adults with normal hydration status is approximately 30-40 ml/kg body weight/d,
      but fluid needs usually increase during fever. Serum electrolyte concentrations
      should be determined prior to PN, and patients with normal fluid and electrolyte
      balance should receive intakes follwing standard recommendations with PN.
      Additional requirements should usually be administered via separate infusion
      pumps. Concentrated potassium (1 mval/ml) or 20% NaCl solutions should be infused
      via a central venous catheter. Electrolyte intake should be adjusted according to
      the results of regular laboratory analyses. Individual determination of
      electrolyte intake is required when electrolyte balance is initially altered
      (e.g. due to chronic diarrhea, recurring vomiting, renal insufficiency etc.).
      Vitamins and trace elements should be generally substituted in PN, unless there
      are contraindications. The supplementation of vitamins and trace elements is
      obligatory after a PN of >1 week. A standard dosage of vitamins and trace
      elements based on current dietary reference intakes for oral feeding is generally
      recommended unless certain clinical situations require other intakes.

PMID- 20049066
TI  - Non-surgical oncology - Guidelines on Parenteral Nutrition, Chapter 19.
AB  - Reduced nutritional state is associated with unfavourable outcomes and a lower
      quality of life in patients with malignancies. Patients with active tumour
      disease frequently have insufficient food intake. The resting energy expenditure
      in cancer patients can be increased, decreased, or remain unchanged compared to
      predicted values. Tumours may result in varying degrees of systemic pro
      inflammatory processes with secondary effects on all significant metabolic
      pathways. Therapeutic objectives are to stabilise nutritional state with
      oral/enteral nutrition and parenteral nutrition (PN) and thus to prevent or
      reduce progressive weight loss. The maintenance or improvement of quality of
      life, and the increase in the effectiveness and a reduction in the side-effects
      of antitumor therapy are further objectives. Indications for PN in tumour
      patients are essentially identical to those in patients with benign illnesses,
      with preference given to oral or enteral nutrition when feasible. A combined
      nutritional concept is preferred if oral or enteral nutrition are possible but
      not sufficient. There are generally no accepted standards for ideal energy and
      nutrient intakes in oncological patients, particularly when exclusive artificial
      nutrition is administered. The use of PN as a general accompaniment to
      radiotherapy or chemotherapy is not indicated, but PN is indicated in chronic
      severe radiogenic enteritis or after allogenic transplantation with pronounced
      mucositis or GvH-related gastrointestinal damage for prolonged periods, with
      particular attention to increased risk of bleeding and infection. No PN is
      necessary in the terminal phase.

PMID- 20049069
TI  - Parenteral nutrition in patients with renal failure - Guidelines on Parenteral
      Nutrition, Chapter 17.
AB  - Partial EN (enteral nutrition) should always be aimed for in patients with renal
      failure that require nutritional support. Nevertheless PN (parenteral nutrition)
      may be necessary in renal failure in patient groups with acute or chronic renal
      failure (ARF or CRF) and additional acute diseases but without extracorporeal
      renal replacement therapy, or in patients with ARF or CRF with additional acute
      diseases on extracorporeal renal replacement therapy, haemodialysis therapy (HD),
      peritoneal dialysis (PD) or continuous renal replacement therapy (CRRT), or in
      patients on HD therapy with intradialytic PN. Patients with renal failure who
      show marked metabolic derangements and changes in nutritional requirements
      require the use of specifically adapted nutrient solutions. The substrate
      requirements of acutely ill, non-hypercatabolic patients with CRF correspond to
      those of patients with ARF who are not receiving any renal replacement patients
      therapy (utilisation of the administered nutrients has to be monitored
      carefully). In ARF patients and acutely ill CRF patients on renal replacement
      therapy, substrate requirements depend on disease severity, type and
      extent/frequency of extracorporeal renal replacement therapy, nutritional status,
      underlying disease and complications occurring during the course of the disease.
      Patients under HD have a higher risk of developing malnutrition. Intradialytic PN
      (IDPN) should be used if causes of malnutrition cannot be eliminated and other
      interventions fail. IDPN should only be carried out when modifiable causes of
      malnutrition are excluded and enhanced oral (like i.e. additional energy drinks)
      or enteral supply is unsuccessful or cannot be carried out.

PMID- 20049070
TI  - Neonatology/Paediatrics - Guidelines on Parenteral Nutrition, Chapter 13.
AB  - There are special challenges in implementing parenteral nutrition (PN) in
      paediatric patients, which arises from the wide range of patients, ranging from
      extremely premature infants up to teenagers weighing up to and over 100 kg, and
      their varying substrate requirements. Age and maturity-related changes of the
      metabolism and fluid and nutrient requirements must be taken into consideration
      along with the clinical situation during which PN is applied. The indication, the
      procedure as well as the intake of fluid and substrates are very different to
      that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy
      needs of premature infants and newborns per kg body weight are markedly higher
      than of older paediatric and adult patients. Premature infants <35 weeks of
      pregnancy and most sick term infants usually require full or partial PN. In
      neonates the actual amount of PN administered must be calculated (not estimated).
      Enteral nutrition should be gradually introduced and should replace PN as quickly
      as possible in order to minimise any side-effects from exposure to PN. Inadequate
      substrate intake in early infancy can cause long-term detrimental effects in
      terms of metabolic programming of the risk of illness in later life. If energy
      and nutrient demands in children and adolescents cannot be met through enteral
      nutrition, partial or total PN should be considered within 7 days or less
      depending on the nutritional state and clinical conditions.

PMID- 20049071
TI  - Amino acids - Guidelines on Parenteral Nutrition, Chapter 4.
AB  - Protein catabolism should be reduced and protein synthesis promoted with
      parenteral nutrion (PN). Amino acid (AA) solutions should always be infused with
      PN. Standard AA solutions are generally used, whereas specially adapted AA
      solutions may be required in certain conditions such as severe disorders of AA
      utilisation or in inborn errors of AA metabolism. An AA intake of 0.8 g/kg/day is
      generally recommended for adult patients with a normal metabolism, which may be
      increased to 1.2-1.5 g/kg/day, or to 2.0 or 2.5 g/kg/day in exceptional cases.
      Sufficient non-nitrogen energy sources should be added in order to assure
      adequate utilisation of AA. A nitrogen calorie ratio of 1:130 to 1:170 (g N/kcal)
      or 1:21 to 1:27 (g AA/kcal) is recommended under normal metabolic conditions. In
      critically ill patients glutamine should be administered parenterally if
      indicated in the form of peptides, for example 0.3-0.4 g glutamine dipeptide/kg
      body weight/day (=0.2-0.26 g glutamine/kg body weight/day). No recommendation can
      be made for glutamine supplementation in PN for patients with acute pancreatitis
      or after bone marrow transplantation (BMT), and in newborns. The application of
      arginine is currently not warranted as a supplement in PN in adults. N-acetyl AA
      are only of limited use as alternative AA sources. There is currently no
      indication for use of AA solutions with an increased content of glycine, branched
      chain AAs (BCAA) and ornithine-alpha-ketoglutarate (OKG) in all patients
      receiving PN. AA solutions with an increased proportion of BCAA are recommended
      in the treatment of hepatic encephalopathy (III-IV).

PMID- 20049073
TI  - Practical handling of AIO admixtures - Guidelines on Parenteral Nutrition,
      Chapter 10.
AB  - All-in-one admixtures (AIO-admixtures) provide safe, effective and low-risk PN
      (parenteral nutrition) for practically all indications and applications. Water,
      energy (carbohydrates and lipids), amino acids, vitamins and trace elements are
      infused together with PN either as industrially-manufactured AIO admixtures
      provided as two- or three-chamber bags (shelf life usually more than 12 months)
      completed with electrolytes and micronutrients where appropriate or as
      individually compounded ready-to-use AIO admixtures (compounding, usually
      prepared by a pharmacy on either a daily or weekly basis and stored at 2-8
      degrees C). Physico-chemical and microbial stability of an AIO admixture is
      essential for the safety and effectiveness of patient-specific PN, and its
      assurance requires specialist pharmaceutical knowledge. The stability should be
      documented for an application period of 24 (-48) hours. It is advisable to offer
      a limited selection of different PN regimes in each hospital. For reasons of drug
      and medication safety, PN admixtures prepared for individual patients must be
      correctly labelled and specifications for storage conditions must also be
      followed during transport. Monitoring is required where applicable.
      Micronutrients are usually administered separately to AIO admixtures. In case
      compatibility and stability have been well documented trace elements and/or
      combination preparations including water-soluble or water-soluble/fat soluble
      vitamin supplements can be added to PN admixtures under strict aseptic
      conditions. AIO admixtures are usually not used as vehicles for drugs
      (incompatibilities).

PMID- 20049072
TI  - Surgery and transplantation - Guidelines on Parenteral Nutrition, Chapter 18.
AB  - In surgery, indications for artificial nutrition comprise prevention and
      treatment of catabolism and malnutrition. Thus in general, food intake should not
      be interrupted postoperatively and the re-establishing of oral (e.g. after
      anastomosis of the colon and rectum, kidney transplantation) or enteral food
      intake (e.g. after an anastomosis in the upper gastrointestinal tract, liver
      transplantation) is recommended within 24 h post surgery. To avoid increased
      mortality an indication for an immediate postoperatively artificial nutrition
      (enteral or parenteral nutrition (PN)) also exists in patients with no signs of
      malnutrition, but who will not receive oral food intake for more than 7 days
      perioperatively or whose oral food intake does not meet their needs (e.g. less
      than 60-80%) for more than 14 days. In cases of absolute contraindication for
      enteral nutrition, there is an indication for total PN (TPN) such as in chronic
      intestinal obstruction with a relevant passage obstruction e.g. a peritoneal
      carcinoma. If energy and nutrient requirements cannot be met by oral and enteral
      intake alone, a combination of enteral and parenteral nutrition is indicated.
      Delaying surgery for a systematic nutrition therapy (enteral and parenteral) is
      only indicated if severe malnutrition is present. Preoperative nutrition therapy
      should preferably be conducted prior to hospital admission to lower the risk of
      nosocomial infections. The recommendations of early postoperative re-establishing
      oral feeding, generally apply also to paediatric patients. Standardised operative
      procedures should be established in order to guarantee an effective nutrition
      therapy.

PMID- 20049074
TI  - Complications and monitoring - Guidelines on Parenteral Nutrition, Chapter 11.
AB  - Compared to enteral or hypocaloric oral nutrition, the use of PN (parenteral
      nutrition) is not associated with increased mortality, overall frequency of
      complications, or longer length of hospital stay (LOS). The risk of PN
      complications (e.g. refeeding-syndrome, hyperglycaemia, bone demineralisation,
      catheter infections) can be minimised by carefully monitoring patients and the
      use of nutrition support teams particularly during long-term PN. Occuring
      complications are e.g. the refeeding-syndrome in patients suffering from severe
      malnutrition with the initiation of refeeding or metabolic, hypertriglyceridemia,
      hyperglycaemia, osteomalacia and osteoporosis, and hepatic complications
      including fatty liver, non-alcoholic fatty liver disease, cholestasis,
      cholecystitis, and cholelithiasis. Efficient monitoring in all types of PN can
      result in reduced PN-associated complications and reduced costs. Water and
      electrolyte balance, blood sugar, and cardiovascular function should regularly be
      monitored during PN. Regular checks of serum electrolytes and triglycerides as
      well as additional monitoring measures are necessary in patients with altered
      renal function, electrolyte-free substrate intake, lipid infusions, and in
      intensive care patients. The metabolic monitoring of patients under long-term PN
      should be carried out according to standardised procedures. Monitoring metabolic
      determinants of bone metabolism is particularly important in patients receiving
      long-term PN. Markers of intermediary, electrolyte and trace element metabolism
      require regular checks.

PMID- 20049075
TI  - Intensive medicine - Guidelines on Parenteral Nutrition, Chapter 14.
AB  - In intensive care patients parenteral nutrition (PN) should not be carried out
      when adequate oral or enteral nutrition is possible. Critically ill patients
      without symptoms of malnutrition, who probably cannot be adequately nourished
      enterally for a period of <5 days, do not require full PN but should be given at
      least a basal supply of glucose. Critically ill patients should be nourished
      parenterally from the beginning of intensive care if they are unlikely to be
      adequately nourished orally or enterally even after 5-7 days. Critically ill and
      malnourished patients should, in addition to a possible partial enteral
      nutrition, be nourished parenterally. Energy supply should not be constant, but
      should be adapted to the stage, the disease has reached. Hyperalimentation should
      be avoided at an acute stage of disease in any case. Critically ill patients
      should be given, as PN, a mixture consisting of amino acids (between 0.8 and 1.5
      g/kg/day), carbohydrates (around 60% of the non-protein energy) and fat (around
      40% of the non-protein energy) as well as electrolytes and micronutrients.

PMID- 20049076
TI  - Guidelines on Parenteral Nutrition from the German Society for Nutritional
      Medicine (DGEM) - overview.

PMID- 20049077
TI  - Gastroenterology - Guidelines on Parenteral Nutrition, Chapter 15.
AB  - In patients with Crohn's disease and ulcerative colitis parenteral nutrition (PN)
      is indicated when enteral nutrition is not possible or should be avoided for
      medical reasons. In Crohn's patients PN is indicated when there are
      signs/symptoms of ileus or subileus in the small intestine, scars or intestinal
      fistulae. PN requires no specific compounding for chronic inflammatory bowel
      diseases. In both diseases it should be composed of 55-60% carbohydrates, 25-30%
      lipids and 10-15% amino acids. PN helps in the correction of malnutrition,
      particularly the intake of energy, minerals, trace elements, deficiency of
      calcium, vitamin D, folic acid, vitamin B12, and zinc. Enteral nutrition is
      clearly superior to PN in severe, acute pancreatitis. An intolerance to enteral
      nutrition results in an indication for total PN in complications such as
      pseudocysts, intestinal and pancreatic fistulae, and pancreatic abscesses or
      pancreatic ascites. If enteral nutrition is not possible, PN is recommended, at
      the earliest, 5 days after admission to the hospital. TPN should not be routinely
      administered in mild acute pancreatitis or nil by moth status <7 days, due to
      high costs and an increased risk of infection. The energy requirements are
      between 25 and 35 kcal/kg body weight/day. A standard solution including lipids
      (monitoring triglyceride levels!) can be administered in acute pancreatitis.
      Glucose (max. 4-5 g/kg body weight/day) and amino acids (about 1.2-1.5 g/kg body
      weight/day) should be administered and the additional enrichment of TPN with
      glutamine should be considered in severe, progressive forms of pancreatitis.

PMID- 20049079
TI  - Ethical and legal points of view in parenteral nutrition - Guidelines on
      Parenteral Nutrition, Chapter 12.
AB  - Adequate nutrition is a part of medical treatment and is influenced by ethical
      and legal considerations. Patients, who cannot be sufficiently fed via the
      gastrointestinal tract, have the fundamental right to receive PN (parenteral
      nutrition) even so patients who are unable to give their consent. General
      objectives in nutrition support are to supply adequate nutrition with regards to
      the prevention of malnutrition and its consequences (increased morbidity and
      mortality), and thereby promoting improved outcome and/or quality of life for the
      patient considering always the patient's needs and wishes. The requests of the
      patient to renounce PN should be respected where a signed living will is helpful.
      During the course of a terminal illness the nutrition has to be adapted
      individually according to the needs and wishes of a patient in the corresponding
      phase. Capability of consent should be checked in each individual case and for
      each measure on an individual basis. Consent should only be accepted if the
      patient is capable of recognizing the nature, meaning and importance of the
      intervention as well as the consequences of relinquishment of such an
      intervention, and is capable to make a self-determined decision. If the patient
      is not capable of consenting, the patient's living will is the most important
      document when determining their assumed will and legally binding. Otherwise a
      guardian appointed by the patient, or the representative appointed by the court
      (if the patient has made no provisions) can make the decision.

PMID- 20049080
TI  - Carbohydrates - Guidelines on Parenteral Nutrition, Chapter 5.
AB  - The main role of carbohydrates in the human body is to provide energy.
      Carbohydrates should always be infused with PN (parenteral nutrition) in
      combination with amino acids and lipid emulsions to improve nitrogen balance.
      Glucose should be provided as a standard carbohydrate for PN, whereas the use of
      xylite is not generally recommended. Fructose solutions should not be used for
      PN. Approximately 60% of non-protein energy should be supplied as glucose with an
      intake of 3.0-3.5 g/kg body weight/day (2.1-2.4 mg/kg body weight/min). In
      patients with a high risk of hyperglycaemia (critically ill, diabetes, sepsis, or
      steroid therapy) an lower initial carbohydrate infusion rate of 1-2 g/kg body
      weight/day is recommended to achieve normoglycaemia. One should aim at reaching a
      blood glucose level of 80-110 mg/dL, and at least a glucose level <145 mg/dL
      should be achieved to reduce morbidity and mortality. Hyperglycaemia may require
      addition of an insulin infusion or a reduction (2.0-3.0 g/kg body weight/day) or
      even a temporary interruption of glucose infusion. Close monitoring of blood
      glucose levels is highly important.

PMID- 20049078
TI  - Lipid emulsions - Guidelines on Parenteral Nutrition, Chapter 6.
AB  - The infusion of lipid emulsions allows a high energy supply, facilitates the
      prevention of high glucose infusion rates and is indispensable for the supply
      with essential fatty acids. The administration of lipid emulsions is recommended
      within < or =7 days after starting PN (parenteral nutrition) to avoid deficiency
      of essential fatty acids. Low-fat PN with a high glucose intake increases the
      risk of hyperglycaemia. In parenterally fed patients with a tendency to
      hyperglycaemia, an increase in the lipid-glucose ratio should be considered. In
      critically ill patients the glucose infusion should not exceed 50% of energy
      intake. The use of lipid emulsions with a low phospholipid/triglyceride ratio is
      recommended and should be provided with the usual PN to prevent depletion of
      essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic
      steatosis. Biologically active vitamin E (alpha-tocopherol) should continuously
      be administered along with lipid emulsions to reduce lipid peroxidation.
      Parenteral lipids should provide about 25-40% of the parenteral non-protein
      energy supply. In certain situations (i.e. critically ill, respiratory
      insufficiency) a lipid intake of up to 50 or 60% of non-protein energy may be
      reasonable. The recommended daily dose for parenteral lipids in adults is 0.7-1.3
      g triglycerides/kg body weight. Serum triglyceride concentrations should be
      monitored regularly with dosage reduction at levels >400 mg/dl (>4.6 mmol/l) and
      interruption of lipid infusion at levels >1000 mg/dl (>11.4 mmol/l). There is
      little evidence at this time that the choice of different available lipid
      emulsions affects clinical endpoints.

PMID- 20049082
TI  - Introduction and methodology - Guidelines on Parenteral Nutrition, Chapter 1.
AB  - Guidelines for Parenteral Nutrition were prepared by the German Society for
      Nutritional Medicine (http://www.dgem.de/), in collaboration with other medical
      associations to provide guidance for quality assurance for parenteral nutrition
      (PN) practice, and to promoting health and quality of life of patients concerned.
      A coordination team proposed topics, working group leaders who along with working
      group members performed systematic literatur searches and drafted recommendations
      in a nominal group process. Recommendations were discussed and agreed upon in a
      structured consensus conference process, followed by a Delphi consensus. The
      current English version of the guidelines was written and updated during the
      period between the last quarter of 2007 and the first quarter of 2009. The
      recommendations of the guidelines should be reviewed, and if necessary updated
      five years after publication.

PMID- 20049081
TI  - Organisation, regulations, preparation and logistics of parenteral nutrition in
      hospitals and homes; the role of the nutrition support team - Guidelines on
      Parenteral Nutrition, Chapter 8.
AB  - PN (parenteral nutrition) should be standardised to ensure quality and to reduce
      complications, and it should be carried out in consultation with a specialised
      nutrition support team whenever possible. Interdisciplinary nutrition support
      teams should be established in all hospitals because effectiveness and efficiency
      in the implementation of PN are increased. The tasks of the team include
      improvements of quality of care as well as enhancing the benefit to cost ratio.
      Therapeutic decisions must be taken by attending physicians, who should
      collaborate with the nutrition support team. "All-in-One" bags are generally
      preferred for PN in hospitals and may be industrially manufactured, industrially
      manufactured with the necessity to add micronutrients, or be prepared "on-demand"
      within or outside the hospital according to a standardised or individual
      composition and under consideration of sterile and aseptic conditions. A
      standardised procedure should be established for introduction and advancement of
      enteral or oral nutrition. Home PN may be indicated if the expected duration of
      when PN exceeds 4 weeks. Home PN is a well established method for providing long
      term PN, which should be indicated by the attending physician and be reviewed by
      the nutrition support team. The care of home PN patients should be standardised
      whenever possible. The indication for home PN should be regularly reviewed during
      the course of PN.

PMID- 20049086
TI  - Revisiting host preference in the Mycobacterium tuberculosis complex:
      experimental infection shows M. tuberculosis H37Rv to be avirulent in cattle.
AB  - Experiments in the late 19th century sought to define the host specificity of the
      causative agents of tuberculosis in mammals. Mycobacterium tuberculosis, the
      human tubercle bacillus, was independently shown by Smith, Koch, and von Behring
      to be avirulent in cattle. This finding was erroneously used by Koch to argue the
      converse, namely that Mycobacterium bovis, the agent of bovine tuberculosis, was
      avirulent for man, a view that was subsequently discredited. However, reports in
      the literature of M. tuberculosis isolation from cattle with tuberculoid lesions
      suggests that the virulence of M. tuberculosis for cattle needs to be
      readdressed. We used an experimental bovine infection model to test the virulence
      of well-characterized strains of M. tuberculosis and M. bovis in cattle, choosing
      the genome-sequenced strains M. tuberculosis H37Rv and M. bovis 2122/97. Cattle
      were infected with approximately 10(6) CFU of M. tuberculosis H37Rv or M. bovis
      2122/97, and sacrificed 17 weeks post-infection. IFN-gamma and tuberculin skin
      tests indicated that both M. bovis 2122 and M. tuberculosis H37Rv were equally
      infective and triggered strong cell-mediated immune responses, albeit with some
      indication of differential antigen-specific responses. Postmortem examination
      revealed that while M. bovis 2122/97-infected animals all showed clear pathology
      indicative of bovine tuberculosis, the M. tuberculosis-infected animals showed no
      pathology. Culturing of infected tissues revealed that M. tuberculosis was able
      to persist in the majority of animals, albeit at relatively low bacillary loads.
      In revisiting the early work on host preference across the M. tuberculosis
      complex, we have shown M. tuberculosis H37Rv is avirulent for cattle, and propose
      that the immune status of the animal, or genotype of the infecting bacillus, may
      have significant bearing on the virulence of a strain for cattle. This work will
      serve as a baseline for future studies into the genetic basis of host preference,
      and in particular the molecular basis of virulence in M. bovis.

PMID- 20049085
TI  - Energy expenditure and energy intake - Guidelines on Parenteral Nutrition,
      Chapter 3.
AB  - The energy expenditure (24h total energy expenditure, TEE) of a healthy
      individual or a patient is a vital reference point for nutritional therapy to
      maintain body mass. TEE is usually determined by measuring resting energy
      expenditure (REE) by indirect calorimetry or by estimation with the help of
      formulae like the formula of Harris and Benedict with an accuracy of +/-20%.
      Further components of TEE (PAL, DIT) are estimated afterwards. TEE in intensive
      care patients is generally only 0-7% higher than REE, due to a low PAL and lower
      DIT. While diseases, like particularly sepsis, trauma and burns, cause a
      clinically relevant increase in REE between 40-80%, in many diseases, TEE is not
      markedly different from REE. A standard formula should not be used in critically
      ill patients, since energy expenditure changes depending on the course and the
      severity of disease. A clinical deterioration due to shock, severe sepsis or
      septic shock may lead to a drop of REE to a level only slightly (20%) above the
      normal REE of a healthy subject. Predominantly immobile patients should receive
      an energy intake between 1.0-1.2 times the determined REE, while immobile
      malnourished patients should receive a stepwise increased intake of 1.1-1.3 times
      the REE over a longer period. Critically ill patients in the acute stage of
      disease should be supplied equal or lower to the current TEE, energy intake
      should be increased stepwise up to 1.2 times (or up to 1.5 times in malnourished
      patients) thereafter.

PMID- 20049084
TI  - Hepatology - Guidelines on Parenteral Nutrition, Chapter 16.
AB  - Parenteral nutrition (PN) is indicated in alcoholic steatohepatitis (ASH) and in
      cirrhotic patients with moderate or severe malnutrition. PN should be started
      immediately when sufficientl oral or enteral feeding is not possible. ASH and
      cirrhosis patients who can be sufficiently fed either orally or enterally, but
      who have to abstain from food over a period of more than 12 hours (including
      nocturnal fasting) should receive basal glucose infusion (2-3 g/kg/d). Total PN
      is required if such fasting periods last longer than 72 h. PN in patients with
      higher-grade hepatic encephalopathy (HE); particularly in HE IV degrees with
      malfunction of swallowing and cough reflexes, and unprotected airways. Cirrhotic
      patients or patients after liver transplantation should receive early
      postoperative PN after surgery if they cannot be sufficiently rally or enterally
      nourished. No recommendation can be made on donor or organ conditioning by
      parenteral administration of glutamine and arginine, aiming at minimising
      ischemia/reperfusion damage. In acute liver failure artificial nutrition should
      be considered irrespective of the nutritional state and should be commenced when
      oral nutrition cannot be restarted within 5 to 7 days. Whenever feasible, enteral
      nutrition should be administered via a nasoduodenal feeding tube.

PMID- 20049088
TI  - Prolonged hypercalcemia following resection of dysgerminoma: a case report.
AB  - Background. Hypercalcemia is a rare but potentially dangerous complication of
      pediatric cancer. Of the dysgerminoma cases reported to date, associated
      hypercalcemia is corrected within 2-7 days of tumor resection. Case. A 13-year
      old female with an ovarian dysgerminoma was found to be hypercalcemic on
      presentation. Following dysgerminoma resection, moderate hypercaclemia persisted
      for 7 days and calcium remained mildly elevated for an additional 7 days. PTHrP
      was undetectable. Immunolocalization studies indicated that 1alpha-hydroxylase
      was expressed in dysgerminoma tissue but 1,25(OH)(2)D(3) was not elevated.
      Conclusion. Persistently elevated calcium levels following tumor resection
      suggests that this case involves a previously undescribed mechanism. Elucidation
      of this mechanism may offer new insights into tumor biology and opportunities for
      therapeutic correction of hypercalcemia in this patient population.

PMID- 20049087
TI  - Clonal characterization of rat muscle satellite cells: proliferation, metabolism
      and differentiation define an intrinsic heterogeneity.
AB  - Satellite cells (SCs) represent a distinct lineage of myogenic progenitors
      responsible for the postnatal growth, repair and maintenance of skeletal muscle.
      Distinguished on the basis of their unique position in mature skeletal muscle,
      SCs were considered unipotent stem cells with the ability of generating a unique
      specialized phenotype. Subsequently, it was demonstrated in mice that opposite
      differentiation towards osteogenic and adipogenic pathways was also possible.
      Even though the pool of SCs is accepted as the major, and possibly the only,
      source of myonuclei in postnatal muscle, it is likely that SCs are not all
      multipotent stem cells and evidences for diversities within the myogenic
      compartment have been described both in vitro and in vivo. Here, by isolating
      single fibers from rat flexor digitorum brevis (FDB) muscle we were able to
      identify and clonally characterize two main subpopulations of SCs: the low
      proliferative clones (LPC) present in major proportion (approximately 75%) and
      the high proliferative clones (HPC), present instead in minor amount
      (approximately 25%). LPC spontaneously generate myotubes whilst HPC differentiate
      into adipocytes even though they may skip the adipogenic program if co-cultured
      with LPC. LPC and HPC differ also for mitochondrial membrane potential
      (DeltaPsi(m)), ATP balance and Reactive Oxygen Species (ROS) generation
      underlying diversities in metabolism that precede differentiation. Notably, SCs
      heterogeneity is retained in vivo. SCs may therefore be comprised of two
      distinct, though not irreversibly committed, populations of cells distinguishable
      for prominent differences in basal biological features such as proliferation,
      metabolism and differentiation. By these means, novel insights on SCs
      heterogeneity are provided and evidences for biological readouts potentially
      relevant for diagnostic purposes described.

PMID- 20049083
TI  - Access technique and its problems in parenteral nutrition - Guidelines on
      Parenteral Nutrition, Chapter 9.
AB  - Catheter type, access technique, and the catheter position should be selected
      considering to the anticipated duration of PN aiming at the lowest complication
      risks (infectious and non-infectious). Long-term (>7-10 days) parenteral
      nutrition (PN) requires central venous access whereas for PN <3 weeks
      percutaneously inserted catheters and for PN >3 weeks subcutaneous tunnelled
      catheters or port systems are appropriate. CVC (central venous catheter) should
      be flushed with isotonic NaCl solution before and after PN application and during
      CVC occlusions. Strict indications are required for central venous access
      placement and the catheter should be removed as soon as possible if not required
      any more. Blood samples should not to be taken from the CVC. If catheter
      infection is suspected, peripheral blood-culture samples and culture samples from
      each catheter lumen should be taken simultaneously. Removal of the CVC should be
      carried out immediately if there are pronounced signs of local infection at the
      insertion site and/or clinical suspicion of catheter-induced sepsis. In case PN
      is indicated for a short period (max. 7-10 days), a peripheral venous access can
      be used if no hyperosmolar solutions (>800 mosm/L) or solutions with a high
      titration acidity or alkalinity are used. A peripheral venous catheter (PVC) can
      remain in situ for as long as it is clinically required unless there are signs of
      inflammation at the insertion site.

PMID- 20049090
TI  - Association between type 2 diabetes loci and measures of fatness.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a metabolic disorder characterized by
      disturbances of carbohydrate, fat and protein metabolism and insulin resistance.
      The majority of T2D patients are obese and obesity by itself may be a cause of
      insulin resistance. Our aim was to evaluate whether the recently identified T2D
      risk alleles are associated with human measures of fatness as characterized with
      Dual Energy X-ray Absorptiometry (DEXA). METHODOLOGY/PRINCIPAL FINDINGS:
      Genotypes and phenotypes of approximately 3,000 participants from cross-sectional
      ERF study were analyzed. Nine single nucleotide polymorphisms (SNPs) in CDKN2AB,
      CDKAL1, FTO, HHEX, IGF2BP2, KCNJ11, PPARG, SLC30A8 and TCF7L2 were genotyped. We
      used linear regression to study association between individual SNPs and the
      combined allelic risk score with body mass index (BMI), fat mass index (FMI), fat
      percentage (FAT), waist circumference (WC) and waist to hip ratio (WHR).
      Significant association was observed between rs8050136 (FTO) and BMI (p = 0.003),
      FMI (p = 0.007) and WC (p = 0.03); fat percentage was borderline significant (p =
      0.053). No other SNPs alone or combined in a risk score demonstrated significant
      association to the measures of fatness. CONCLUSIONS/SIGNIFICANCE: From the
      recently identified T2D risk variants only the risk variant of the FTO gene
      (rs8050136) showed statistically significant association with BMI, FMI, and WC.

PMID- 20049089
TI  - Diacylglycerol-stimulated endocytosis of transferrin in trypanosomatids is
      dependent on tyrosine kinase activity.
AB  - Small molecule regulation of cell function is an understudied area of
      trypanosomatid biology. In Trypanosoma brucei diacylglycerol (DAG) stimulates
      endocytosis of transferrin (Tf). However, it is not known whether other
      trypanosomatidae respond similarly to the lipid. Further, the biochemical
      pathways involved in DAG signaling to the endocytic system in T. brucei are
      unknown, as the parasite genome does not encode canonical DAG receptors (e.g. C1
      domains). We established that DAG stimulates endocytosis of Tf in Leishmania
      major, and we evaluated possible effector enzymes in the pathway with multiple
      approaches. First, a heterologously expressed glycosylphosphatidylinositol
      phospholipase C (GPI-PLC) activated endocytosis of Tf 300% in L. major. Second,
      exogenous phorbol ester and DAGs promoted Tf endocytosis in L. major. In search
      of possible effectors of DAG signaling, we discovered a novel C1-like domain
      (i.e. C1_5) in trypanosomatids, and we identified protein Tyr kinases (PTKs)
      linked with C1_5 domains in T. brucei, T. cruzi, and L. major. Consequently, we
      hypothesized that trypanosome PTKs might be effector enzymes for DAG signaling.
      General uptake of Tf was reduced by inhibitors of either Ser/Thr or Tyr kinases.
      However, DAG-stimulated endocytosis of Tf was blocked only by an inhibitor of
      PTKs, in both T. brucei and L. major. We conclude that (i) DAG activates Tf
      endocytosis in L. major, and that (ii) PTKs are effectors of DAG-stimulated
      endocytosis of Tf in trypanosomatids. DAG-stimulated endocytosis of Tf may be a
      T. brucei adaptation to compete effectively with host cells for vertebrate Tf in
      blood, since DAG does not enhance endocytosis of Tf in human cells.

PMID- 20049091
TI  - Intraseasonal dynamics and dominant sequences in H3N2 influenza.
AB  - Long-term influenza evolution has been well studied, but the patterns of sequence
      diversity within seasons are less clear. H3N2 influenza genomes sampled from New
      York State over ten years indicated intraseasonal changes in evolutionary
      dynamics. Using the mean Hamming distance of a set of amino acid or nucleotide
      sequences as an indicator of its diversity, we found that influenza sequence
      diversity was significantly higher during the early epidemic period than later in
      the influenza season. Diversity was lowest during the peak of the epidemic, most
      likely due to the high prevalence of a single dominant amino acid sequence or
      very few dominant sequences during the peak epidemic period, corresponding with
      rapid expansion of the viral population. The frequency and duration of dominant
      sequences varied by influenza protein, but all proteins had an abundance of one
      distinct sequence during the peak epidemic period. In New York State from 1995 to
      2005, high sequence diversity during the early epidemic suggested that seasonal
      antigenic drift could have occurred primarily in this period, followed by a
      clonal expansion of typically one clade during the peak of the epidemic, possibly
      indicating a shift to neutral drift or purifying selection.

PMID- 20049092
TI  - Male sexual dysfunction: diagnosis and treatment from a sexological and
      interdisciplinary perspective.
AB  - BACKGROUND: Among all types of sexual disturbance in men, disturbances of sexual
      function are the most important in clinical practice. These are classified by the
      segment of the sexual reaction cycle in which they arise (appetence, arousal,
      orgasm, and resolution). Partial functional impairment must be distinguished from
      dysfunction causing significant suffering and requiring treatment. METHODS: The
      authors' clinical experience is supplemented with a selective review of the
      literature on sexual dysfunction, its association with underlying diseases, and
      its impact on sexual and relational satisfaction. RESULTS: The sexual history
      (including the partner's sexual history, as far as this can be obtained) is of
      prime importance in the diagnostic evaluation of sexual disturbances. This
      evaluation must take the multidimensionality and multiple functions of human
      sexuality into account. Chronic frustration of the fundamental psychosocial needs
      for acceptance, closeness, and security is a very important factor that has been
      neglected until now by the prevailing conceptions of the etiology and
      pathogenesis of sexual disturbances. Their treatment involves a combination of
      elements from sexual medicine and psychotherapy, along with somatic medical and
      pharmacotherapeutic intervention, if needed. The goal of syndyastic sex therapy,
      a further development of the previous therapies, is to fulfill these fundamental
      needs and thereby to improve the patient's sexual function and deepen his
      satisfaction with the relationship in its entirety. CONCLUSIONS: It is essential
      to understand the different types of sexual disturbance in their biopsychosocial
      context as well as the significance of sexuality for the individual, and for the
      couple, with respect to reproduction, sexual pleasure, and bonding. Sexual
      disturbances are common, and patients therefore expect their physicians to be
      proficient in sexual medicine. The coverage of this subject in both undergraduate
      and postgraduate medical education in Germany needs to be improved.

PMID- 20049093
TI  - The price of hope: is autologous cord blood storage necessary and useful?

PMID- 20049094
TI  - Stem cells derived from cord blood in transplantation and regenerative medicine.
AB  - BACKGROUND: Physicians of any specialty may be the first persons to whom
      prospective parents turn for information about the acquisition and storage of
      stem cells derived from cord blood. Stem cells can potentially be used to treat
      many diseases, yet they are not a panacea. This article provides an overview of
      their current and possible future applications. METHODS: Original papers were
      retrieved by a selective search of the literature, and the Internet sites and
      advertising brochures of private stem cell banks were also examined. RESULTS:
      Allogeneic hematopoietic stem cells derived from umbilical cord blood (obtained
      from healthy donors, rather than from the patient to be treated) have been in
      routine use worldwide for more than ten years in the treatment of hematopoietic
      diseases. Experiments in cell culture and in animal models suggest that these
      cells might be of therapeutic use in regenerative medicine, but also show that
      this potential can be realized only if the cells are not cryopreserved. There is
      as yet no routine clinical application of autologous hematopoietic stem cells
      from cord blood (self-donation of blood), even though cord blood has been stored
      in private banks for more than ten years. CONCLUSIONS: Autologous stem cells from
      cord blood have poor prospects for use in regenerative medicine, because they
      have to be cryopreserved until use. Physicians should tell prospective parents
      that they have no reason to feel guilty if they choose not to store cord blood in
      a private bank.

PMID- 20049095
TI  - Applying research to public health questions: timing and the environmentally
      relevant dose.

PMID- 20049096
TI  - Good laboratory practices and safety assessments.

PMID- 20049098
TI  - Electromagnetic fields and the precautionary principle.

PMID- 20049100
TI  - Electromagnetic fields: Conference, hearing call up cell phone use.

PMID- 20049101
TI  - Drinking water quality: Better biomarker of DBP exposure.

PMID- 20049103
TI  - Materials science: Bringing biolubricants to industry.

PMID- 20049104
TI  - Invasive species: Pallet-able change in Canada.

PMID- 20049105
TI  - Trash or treasure? Putting coal combustion waste to work.

PMID- 20049106
TI  - Balancing act: creating the right regulation for coal combustion waste.

PMID- 20049107
TI  - Sentinel symptoms of climate change: indicators for related health effects.

PMID- 20049108
TI  - Micro management: understanding how diesel exhaust particles alter cellular
      processes.

PMID- 20049109
TI  - You are where you live: the interrelationship of air pollution, address, and
      walkability.

PMID- 20049110
TI  - Delivering new data: local traffic pollution and pregnancy outcomes.

PMID- 20049111
TI  - Does rapid metabolism ensure negligible risk from bisphenol A?
AB  - BACKGROUND: Bisphenol A (BPA) risks are being evaluated by many regulatory bodies
      because exposure is widespread and the potential exists for toxicity at low
      doses. OBJECTIVE: We evaluated evidence that BPA is cleared more rapidly in
      humans than in rats in relation to BPA risk assessment. DISCUSSION: The European
      Food Safety Authority (EFSA) relied on pharmacokinetic evidence to conclude that
      rodent toxicity data are not directly relevant to human risk assessment. Further,
      the EFSA argues that rapid metabolism will result in negligible exposure during
      the perinatal period because of BPA glucuronidation in pregnant women or
      sulfation in newborns. These arguments fail to consider the deconjugation of BPA
      glucuronide in utero by beta-glucuronidase, an enzyme that is present in high
      concentrations in placenta and various other tissues. Further, arylsulfatase C,
      which reactivates endogenous sulfated estrogens, develops early in life and so
      may deconjugate BPA sulfate in newborns. Biomonitoring studies and laboratory
      experiments document free BPA in rat and human maternal, placental, and fetal
      tissues, indicating that human BPA exposure is not negligible. The pattern of
      these detections is consistent with deconjugation in the placenta, resulting in
      fetal exposure. The tolerable daily intake set by the EFSA (0.05 mg/kg/day) is
      well above effect levels reported in some animal studies. CONCLUSION: This
      potential risk should not be dismissed on the basis of an uncertain
      pharmacokinetic argument. Rather, risk assessors need to decipher the BPA dose
      response and apply it to humans with comprehensive pharmacokinetic models that
      account for metabolite deconjugation.

PMID- 20049112
TI  - Basic exploratory research versus guideline-compliant studies used for hazard
      evaluation and risk assessment: bisphenol A as a case study.
AB  - BACKGROUND: Myers et al. [Environ Health Perspect 117:309-315 (2009)] argued that
      Good Laboratory Practices (GLPs) cannot be used as a criterion for selecting data
      for risk assessment, using bisphenol A (BPA) as a case study. They did not
      discuss the role(s) of guideline-compliant studies versus basic/exploratory
      research studies, and they criticized both GLPs and guideline-compliant studies
      and their roles in formal hazard evaluation and risk assessment. They also
      specifically criticized our published guideline-compliant dietary studies on BPA
      in rats and mice and 17beta-estradiol (E(2)) in mice. OBJECTIVES: As the study
      director/first author of the criticized E(2) and BPA studies, I discuss the uses
      of basic research versus guideline-compliant studies, how testing guidelines are
      developed and revised, how new end points are validated, and the role of GLPs. I
      also provide an overview of the BPA guideline-compliant and exploratory research
      animal studies and describe BPA pharmacokinetics in rats and humans. I present
      responses to specific criticisms by Myers et al. DISCUSSION AND CONCLUSIONS:
      Weight-of-evidence evaluations have consistently concluded that low-level BPA
      oral exposures do not adversely affect human developmental or reproductive
      health, and I encourage increased validation efforts for "new" end points for
      inclusion in guideline studies, as well as performance of robust long-term
      studies to follow early effects (observed in small exploratory studies) to any
      adverse consequences.

PMID- 20049113
TI  - A clash of old and new scientific concepts in toxicity, with important
      implications for public health.
AB  - BACKGROUND: A core assumption of current toxicologic procedures used to establish
      health standards for chemical exposures is that testing the safety of chemicals
      at high doses can be used to predict the effects of low-dose exposures, such as
      those common in the general population. This assumption is based on the precept
      that "the dose makes the poison": higher doses will cause greater effects.
      OBJECTIVES: We challenge the validity of assuming that high-dose testing can be
      used to predict low-dose effects for contaminants that behave like hormones. We
      review data from endocrinology and toxicology that falsify this assumption and
      summarize current mechanistic understanding of how low doses can lead to effects
      unpredictable from high-dose experiments. DISCUSSION: Falsification of this
      assumption raises profound issues for regulatory toxicology. Many exposure
      standards are based on this assumption. Rejecting the assumption will require
      that these standards be reevaluated and that procedures employed to set health
      standards be changed. The consequences of these changes may be significant for
      public health because of the range of health conditions now plausibly linked to
      exposure to endocrine-disrupting contaminants. CONCLUSIONS: We recommend that
      procedures to establish acceptable exposure levels for endocrine-disrupting
      compounds incorporate the inability for high-dose tests to predict low-dose
      results. Setting acceptable levels of exposure must include testing for health
      consequences at prevalent levels of human exposure, not extrapolations from the
      effects observed in high-dose experiments. Scientists trained in endocrinology
      must be engaged systematically in standard setting for endocrine-disrupting
      compounds.

PMID- 20049114
TI  - Global status of DDT and its alternatives for use in vector control to prevent
      disease.
AB  - OBJECTIVE: I review the status of dichlorodiphenyltrichloroethane (DDT), used for
      disease vector control, along with current evidence on its benefits and risks in
      relation to the available alternatives. DATA SOURCES AND EXTRACTION: Contemporary
      data on DDT use were largely obtained from questionnaires and reports. I also
      conducted a Scopus search to retrieve published articles. DATA SYNTHESIS: DDT has
      been recommended as part of the arsenal of insecticides available for indoor
      residual spraying until suitable alternatives are available. Approximately 14
      countries use DDT for disease control, and several countries are preparing to
      reintroduce DDT. The effectiveness of DDT depends on local settings and merits
      close consideration in relation to the alternatives. Concerns about the continued
      use of DDT are fueled by recent reports of high levels of human exposure
      associated with indoor spraying amid accumulating evidence on chronic health
      effects. There are signs that more malaria vectors are becoming resistant to the
      toxic action of DDT, and that resistance is spreading to new countries. A
      comprehensive cost assessment of DDT versus its alternatives that takes side
      effects into account is missing. Effective chemical methods are available as
      immediate alternatives to DDT, but the choice of insecticide class is limited,
      and in certain areas the development of resistance is undermining the efficacy of
      insecticidal tools. New insecticides are not expected in the short term.
      Nonchemical methods are potentially important, but their effectiveness at program
      level needs urgent study. CONCLUSIONS: To reduce reliance on DDT, support is
      needed for integrated and multipartner strategies of vector control and for the
      continued development of new technologies. Integrated vector management provides
      a framework for developing and implementing effective technologies and strategies
      as sustainable alternatives to reliance on DDT.

PMID- 20049115
TI  - A reexamination of the PPAR-alpha activation mode of action as a basis for
      assessing human cancer risks of environmental contaminants.
AB  - BACKGROUND: Diverse environmental contaminants, including the plasticizer di(2
      ethylhexyl)phthalate (DEHP), are hepatocarcinogenic peroxisome proliferators in
      rodents. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation
      and its sequelae have been proposed to constitute a mode of action (MOA) for
      hepatocarcinogenesis by such agents as a sole causative factor. Further, based on
      a hypothesized lower sensitivity of humans to this MOA, prior reviews have
      concluded that rodent hepatocarcinogenesis by PPAR-alpha agonists is irrelevant
      to human carcinogenic risk. DATA SYNTHESIS: Herein, we review recent studies that
      experimentally challenge the PPAR-alpha activation MOA hypothesis, providing
      evidence that DEHP is hepatocarcinogenic in PPAR-alpha-null mice and that the MOA
      but not hepatocarcinogenesis is evoked by PPAR-alpha activation in a transgenic
      mouse model. We further examine whether relative potency for PPAR-alpha
      activation or other steps in the MOA correlates with tumorigenic potency. In
      addition, for most PPAR-alpha agonists of environmental concern, available data
      are insufficient to characterize relative human sensitivity to this rodent MOA or
      to induction of hepatocarcinogenesis. CONCLUSIONS: Our review and analyses raise
      questions about the hypothesized PPAR-alpha activation MOA as a sole explanation
      for rodent hepatocarcinogenesis by PPAR-alpha agonists and therefore its utility
      as a primary basis for assessing human carcinogenic risk from the diverse
      compounds that activate PPAR-alpha. These findings have broad implications for
      how MOA hypotheses are developed, tested, and applied in human health risk
      assessment. We discuss alternatives to the current approaches to these key
      aspects of mechanistic data evaluation.

PMID- 20049116
TI  - Environmental health indicators of climate change for the United States: findings
      from the State Environmental Health Indicator Collaborative.
AB  - OBJECTIVE: To develop public health adaptation strategies and to project the
      impacts of climate change on human health, indicators of vulnerability and
      preparedness along with accurate surveillance data on climate-sensitive health
      outcomes are needed. We researched and developed environmental health indicators
      for inputs into human health vulnerability assessments for climate change and to
      propose public health preventative actions. DATA SOURCES: We conducted a review
      of the scientific literature to identify outcomes and actions that were related
      to climate change. Data sources included governmental and nongovernmental
      agencies and the published literature. DATA EXTRACTION: Sources were identified
      and assessed for completeness, usability, and accuracy. Priority was then given
      to identifying longitudinal data sets that were applicable at the state and
      community level. DATA SYNTHESIS: We present a list of surveillance indicators for
      practitioners and policy makers that include climate-sensitive health outcomes
      and environmental and vulnerability indicators, as well as mitigation,
      adaptation, and policy indicators of climate change. CONCLUSIONS: A review of
      environmental health indicators for climate change shows that data exist for many
      of these measures, but more evaluation of their sensitivity and usefulness is
      needed. Further attention is necessary to increase data quality and availability
      and to develop new surveillance databases, especially for climate-sensitive
      morbidity.

PMID- 20049117
TI  - Comparative toxicity of size-fractionated airborne particulate matter collected
      at different distances from an urban highway.
AB  - BACKGROUND: Epidemiologic studies have reported an association between proximity
      to highway traffic and increased cardiopulmonary illnesses. OBJECTIVES: We
      investigated the effect of size-fractionated particulate matter (PM), obtained at
      different distances from a highway, on acute cardiopulmonary toxicity in mice.
      METHODS: We collected PM for 2 weeks in July-August 2006 using a three-stage
      (ultrafine, < 0.1 microm; fine, 0.1-2.5 microm; coarse, 2.5-10 microm) high
      volume impactor at distances of 20 m [near road (NR)] and 275 m [far road (FR)]
      from an interstate highway in Raleigh, North Carolina. Samples were extracted in
      methanol, dried, diluted in saline, and then analyzed for chemical constituents.
      Female CD-1 mice received either 25 or 100 microg of each size fraction via
      oropharyngeal aspiration. At 4 and 18 hr postexposure, mice were assessed for
      pulmonary responsiveness to inhaled methacholine, biomarkers of lung injury and
      inflammation; ex vivo cardiac pathophysiology was assessed at 18 hr only.
      RESULTS: Overall chemical composition between NR and FR PM was similar, although
      NR samples comprised larger amounts of PM, endotoxin, and certain metals than did
      the FR samples. Each PM size fraction showed differences in ratios of major
      chemical classes. Both NR and FR coarse PM produced significant pulmonary
      inflammation irrespective of distance, whereas both NR and FR ultrafine PM
      induced cardiac ischemia-reperfusion injury. CONCLUSIONS: On a comparative mass
      basis, the coarse and ultrafine PM affected the lung and heart, respectively. We
      observed no significant differences in the overall toxicity end points and
      chemical makeup between the NR and FR PM. The results suggest that PM of
      different size-specific chemistry might be associated with different toxicologic
      mechanisms in cardiac and pulmonary tissues.

PMID- 20049118
TI  - Spatial modeling of PM10 and NO2 in the continental United States, 1985-2000.
AB  - BACKGROUND: Epidemiologic studies of air pollution have demonstrated a link
      between long-term air pollution exposures and mortality. However, many have been
      limited to city-specific average pollution measures or spatial or land-use
      regression exposure models in small geographic areas. OBJECTIVES: Our objective
      was to develop nationwide models of annual exposure to particulate matter < 10
      microm in diameter (PM(10)) and nitrogen dioxide during 1985-2000. METHODS: We
      used generalized additive models (GAMs) to predict annual levels of the
      pollutants using smooth spatial surfaces of available monitoring data and
      geographic information system-derived covariates. Model performance was
      determined using a cross-validation (CV) procedure with 10% of the data. We also
      compared the results of these models with a commonly used spatial interpolation,
      inverse distance weighting. RESULTS: For PM(10), distance to road, elevation,
      proportion of low-intensity residential, high-intensity residential, and
      industrial, commercial, or transportation land use within 1 km were all
      statistically significant predictors of measured PM(10) (model R(2) = 0.49, CV
      R(2) = 0.55). Distance to road, population density, elevation, land use, and
      distance to and emissions of the nearest nitrogen oxides-emitting power plant
      were all statistically significant predictors of measured NO(2) (model R(2) =
      0.88, CV R(2) = 0.90). The GAMs performed better overall than the inverse
      distance models, with higher CV R(2) and higher precision. CONCLUSIONS: These
      models provide reasonably accurate and unbiased estimates of annual exposures for
      PM(10) and NO(2). This approach provides the spatial and temporal variability
      necessary to describe exposure in studies assessing the health effects of chronic
      air pollution.

PMID- 20049119
TI  - The short-chain fatty acid methoxyacetic acid disrupts endogenous estrogen
      receptor-alpha-mediated signaling.
AB  - BACKGROUND: Ethylene glycol monomethyl ether (EGME) exposure is associated with
      impaired reproductive function. The primary metabolite of EGME is methoxyacetic
      acid (MAA), a short-chain fatty acid that inhibits histone deacetylase activity
      and alters gene expression. OBJECTIVE: Because estrogen signaling is necessary
      for normal reproductive function and modulates gene expression, the estrogen
      signaling pathway is a likely target for MAA; however, little is known about the
      effects of MAA in this regard. METHODS: We evaluated the mechanistic effects of
      MAA on estrogen receptor (ER) expression and estrogen signaling using in vitro
      and in vivo model systems. RESULTS: MAA potentiates 17beta-estradiol (E(2))
      stimulation of an estrogen-responsive reporter plasmid in HeLa cells transiently
      transfected with either a human ERalpha or ERbeta expression vector containing a
      cytomegalovirus (CMV) promoter. This result is attributed to increased exogenous
      ER expression due to MAA-mediated activation of the CMV promoter. In contrast to
      its effects on exogenous ER, MAA decreases endogenous ERalpha expression and
      attenuates E(2)-stimulated endogenous gene expression in both MCF-7 cells and the
      mouse uterus. CONCLUSIONS: These results illustrate the importance of careful
      experimental design and analysis when assessing the potential endocrine
      disrupting properties of a compound to ensure biological responses are in
      concordance with in vitro analyses. Given the established role of the ER in
      normal reproductive function, the effects of MAA on the endogenous ER reported
      here are consistent with the reproductive abnormalities observed after EGME
      exposure and suggest that these toxicities may be due, at least in part, to
      attenuation of endogenous ER-mediated signaling.

PMID- 20049120
TI  - Chronic fine and coarse particulate exposure, mortality, and coronary heart
      disease in the Nurses' Health Study.
AB  - BACKGROUND: The relationship of fine particulate matter < 2.5 microm in diameter
      (PM(2.5)) air pollution with mortality and cardiovascular disease is well
      established, with more recent long-term studies reporting larger effect sizes
      than earlier long-term studies. Some studies have suggested the coarse fraction,
      particles between 2.5 and 10 microm (PM(10-2.5)), may also be important. With
      respect to mortality and cardiovascular events, questions remain regarding the
      relative strength of effect sizes for chronic exposure to fine and coarse
      particles. OBJECTIVES: We examined the relationship of chronic PM(2.5) and PM(10
      2.5) exposures with all-cause mortality and fatal and nonfatal incident coronary
      heart disease (CHD), adjusting for time-varying covariates. METHODS: The current
      study included women from the Nurses' Health Study living in metropolitan areas
      of the northeastern and midwestern United States. Follow-up was from 1992 to
      2002. We used geographic information systems-based spatial smoothing models to
      estimate monthly exposures at each participant's residence. RESULTS: We found
      increased risk of all-cause mortality [hazard ratio (HR), 1.26; 95% confidence
      interval (CI), 1.02-1.54] and fatal CHD (HR = 2.02; 95% CI, 1.07-3.78) associated
      with each 10-microg/m(3) increase in annual PM(2.5) exposure. The association
      between fatal CHD and PM(10-2.5) was weaker. CONCLUSIONS: Our findings contribute
      to growing evidence that chronic PM(2.5) exposure is associated with risk of all
      cause and cardiovascular mortality.

PMID- 20049121
TI  - Exposure to hexabromocyclododecanes (HBCDs) via dust ingestion, but not diet,
      correlates with concentrations in human serum: preliminary results.
AB  - BACKGROUND: Hexabromocyclododecane (HBCD) is a high-production-volume chemical
      used as flame retardant in polystyrene insulation and textiles. Because it is not
      chemically bound to the polymer, HBCD can migrate into the environment,
      contaminating indoor dust and foodstuff. OBJECTIVES: We examined for the first
      time the relationship between combined exposure to three HBCD isomers
      (SigmaHBCDs) via ingestion of food (duplicate diets) and indoor dust and HBCD
      concentrations in serum for 16 Belgian adults (20-25 years of age). We also
      determined the chiral signatures of HBCDs to advance understanding of source-to
      human enantioselective degradation and/or metabolism. METHODS: Concentrations and
      chiral signatures of alpha-, beta-, and gamma-HBCD in duplicate diets, dust, and
      serum were measured by liquid chromatography/tandem mass spectrometry. RESULTS:
      Dietary intakes of SigmaHBCDs were 1.2-20 ng/day (average, 7.2 ng/day), whereas
      those estimated under average (20 mg dust/day) and high (50 mg dust/day) dust
      ingestion scenarios were 1.1-15 ng/day (average intake, 3.2 ng/day) and 2.8-38
      ng/day (average intake, 8.0 ng/day), respectively. Concentrations of SigmaHBCDs
      measured in blood serum were < 0.5 to 11 ng/g lipid weight (lw) (average, 2.9
      ng/g lw). Gamma-HBCD dominated in food, whereas alpha-HBCD dominated in dust and
      was the sole isomer in serum. Although exposure via dust ingestion correlated
      significantly (p < 0.01) with concentrations in serum, no such correlation was
      evident with dietary exposure (p > 0.1). Although no enantioselective enrichment
      was detected in either dust or diet, substantial enrichment of (-)alpha-HBCD was
      observed in serum. CONCLUSIONS: Serum concentrations of HBCDs were correlated
      with the exposure via dust, but not via dietary ingestion. The enrichment of the
      (-)alpha-HBCD enantiomer in humans appears to be due to in vivo enantioselective
      metabolism/excretion rather than ingestion of dust or diet.

PMID- 20049122
TI  - Saliva cortisol and exposure to aircraft noise in six European countries.
AB  - BACKGROUND: Several studies show an association between exposure to aircraft or
      road traffic noise and cardiovascular effects, which may be mediated by a noise
      induced release of stress hormones. OBJECTIVE: Our objective was to assess saliva
      cortisol concentration in relation to exposure to aircraft noise. METHOD: A
      multicenter cross-sectional study, HYENA (Hypertension and Exposure to Noise near
      Airports), comprising 4,861 persons was carried out in six European countries. In
      a subgroup of 439 study participants, selected to enhance the contrast in
      exposure to aircraft noise, saliva cortisol was assessed three times (morning,
      lunch, and evening) during 1 day. RESULTS: We observed an elevation of 6.07
      nmol/L [95% confidence interval (CI), 2.32-9.81 nmol/L] in morning saliva
      cortisol level in women exposed to aircraft noise at an average 24-hr sound level
      (L(Aeq,24h)) > 60 dB, compared with women exposed to L(Aeq,24h) < or = 50 dB,
      corresponding to an increase of 34%. Employment status appeared to modify the
      response. We found no association between noise exposure and saliva cortisol
      levels in men. CONCLUSIONS: Our results suggest that exposure to aircraft noise
      increases morning saliva cortisol levels in women, which could be of relevance
      for noise-related cardiovascular effects.

PMID- 20049123
TI  - Lung cancer in a U.S. population with low to moderate arsenic exposure.
AB  - BACKGROUND: Little is known about the carcinogenic potential of arsenic in areas
      with low to moderate concentrations of arsenic (< 100 microg/L) in drinking
      water. OBJECTIVES: We examined associations between arsenic and lung cancer.
      METHODS: A population-based case-control study of primary incident lung cancer
      was conducted in 10 counties in two U.S. states, New Hampshire and Vermont. The
      study included 223 lung cancer cases and 238 controls, each of whom provided
      toenail clippings for arsenic exposure measurement by inductively coupled-plasma
      mass spectrometry. We estimated odds ratios (ORs) of the association between
      arsenic exposure and lung cancer using unconditional logistic regression with
      adjustment for potential confounders (age, sex, race/ethnicity, smoking pack
      years, education, body mass index, fish servings per week, and toenail selenium
      level). RESULTS: Arsenic exposure was associated with small-cell and squamous
      cell carcinoma of the lung [OR = 2.75; 95% confidence interval (CI), 1.00-7.57]
      for toenail arsenic concentration > or = 0.114 microg/g, versus < 0.05 microg/g.
      A history of lung disease (bronchitis, chronic obstructive pulmonary disease, or
      fibrosis) was positively associated with lung cancer (OR = 2.86; 95% CI, 1.39
      5.91). We also observed an elevated risk of lung cancer among participants with a
      history of lung disease and toenail arsenic > or = 0.05 microg/g (OR = 4.78; 95%
      CI, 1.87-12.2) than among individuals with low toenail arsenic and no history of
      lung disease. CONCLUSION: Although this study supports the possibility of an
      increased risk of specific lung cancer histologic types at lower levels of
      arsenic exposure, we recommend large-scale population-based studies.

PMID- 20049124
TI  - Influence of cobalamin on arsenic metabolism in Bangladesh.
AB  - BACKGROUND: Arsenic is a carcinogen to which 35 million people in Bangladesh are
      chronically exposed. The enzymatic transfer of methyl groups to inorganic As
      (iAs) generates monomethylarsonic (MMA) and dimethylarsinic acids (DMA) and
      facilitates urinary As (uAs) elimination. This process is dependent on one-carbon
      metabolism, a pathway in which folate and cobalamin have essential roles in the
      recruitment and transfer of methyl groups. Although DMA(V) is the least toxic
      metabolite, increasing evidence suggests that MMA(III) may be the most cytotoxic
      and genotoxic As intermediary metabolite. OBJECTIVE: We examined the associations
      between plasma cobalamin and uAs metabolites. METHODS: We conducted a cross
      sectional study of 778 Bangladeshi adults in which we over-sampled cobalamin
      deficient participants. Participants provided blood samples for the measurement
      of plasma cobalamin and urine specimens for As measurements. RESULTS: Cobalamin
      was inversely associated with the proportion of total uAs excreted as iAs (%iAs)
      [unstandardized regression coefficient (b) = -0.10; 95% confidence interval (CI),
      -0.17 to -0.02; p = 0.01] and positively associated with %MMA (b = 0.12; 95% CI,
      0.05 to 0.20; p = 0.001). Both of these associations were stronger among folate
      sufficient participants (%iAs: b = -0.17; 95% CI, -0.30 to -0.03; p = 0.02. %MMA:
      b = 0.20; 95% CI, 0.11 to 0.30; p < 0.0001), and the differences by folate status
      were statistically significant. CONCLUSIONS: In this group of Bangladeshi adults,
      cobalamin appeared to facilitate the first As methylation step among folate
      sufficient individuals. Given the toxicity of MMA(III), our findings suggest that
      in contrast to folate, cobalamin may not favorably influence As metabolism.

PMID- 20049125
TI  - Mapping community determinants of heat vulnerability.
AB  - BACKGROUND: The evidence that heat waves can result in both increased deaths and
      illness is substantial, and concern over this issue is rising because of climate
      change. Adverse health impacts from heat waves can be avoided, and epidemiologic
      studies have identified specific population and community characteristics that
      mark vulnerability to heat waves. OBJECTIVES: We situated vulnerability to heat
      in geographic space and identified potential areas for intervention and further
      research. METHODS: We mapped and analyzed 10 vulnerability factors for heat
      related morbidity/mortality in the United States: six demographic characteristics
      and two household air conditioning variables from the U.S. Census Bureau,
      vegetation cover from satellite images, and diabetes prevalence from a national
      survey. We performed a factor analysis of these 10 variables and assigned values
      of increasing vulnerability for the four resulting factors to each of 39,794
      census tracts. We added the four factor scores to obtain a cumulative heat
      vulnerability index value. RESULTS: Four factors explained > 75% of the total
      variance in the original 10 vulnerability variables: a) social/environmental
      vulnerability (combined education/poverty/race/green space), b) social isolation,
      c) air conditioning prevalence, and d) proportion elderly/diabetes. We found
      substantial spatial variability of heat vulnerability nationally, with generally
      higher vulnerability in the Northeast and Pacific Coast and the lowest in the
      Southeast. In urban areas, inner cities showed the highest vulnerability to heat.
      CONCLUSIONS: These methods provide a template for making local and regional heat
      vulnerability maps. After validation using health outcome data, interventions can
      be targeted at the most vulnerable populations.

PMID- 20049126
TI  - A novel approach using DNA-repair-deficient chicken DT40 cell lines for screening
      and characterizing the genotoxicity of environmental contaminants.
AB  - BACKGROUND: Many bacterial or mammalian cell-based test systems, such as the Ames
      test, chromosomal aberration assays, or gene mutation assays, are commonly used
      in developed countries to detect the genotoxicity of industrial chemicals.
      However, the specificity is generally limited and the sensitivity is not
      sufficiently high. In addition, most assays cannot provide information on
      mechanisms of genotoxicity of a given chemical. OBJECTIVES: We aimed to establish
      a sensitive and fast screening method that is also capable of characterizing
      mechanisms of genotoxicity. METHODS: We developed a novel bioassay employing gene
      disrupted clones of the chicken DT40 B-lymphocyte line, which are designed to be
      deficient in several specific DNA repair pathways. Genotoxic chemicals can delay
      cellular proliferation in DNA-repair-deficient clones more significantly than in
      wild-type cells by interfering with DNA replication, thereby inducing DNA damage.
      In addition, we verified the validity of this assay by analyzing the genotoxicity
      of gamma-rays, ultraviolet (UV) light, and sodium metaarsenite (NaAsO(2)). We
      also characterized DNA lesions induced by NaAsO(2). RESULTS: Genotoxicity of
      given stressors was successfully screened based on a comparison of proliferation
      kinetics between wild-type and DNA-repair-deficient mutants in 48 hr. We also
      found that NaAsO(2) apparently induces at least two types of damage: chromosomal
      breaks and UV photoproduct-like DNA lesions. CONCLUSION: This bioassay is a
      reliable and sensitive screening tool for environmental mutagens as well as for
      further characterizing the nature of detected genotoxicity.

PMID- 20049127
TI  - Disruption of microRNA expression in human airway cells by diesel exhaust
      particles is linked to tumorigenesis-associated pathways.
AB  - BACKGROUND: Particulate matter (PM) is associated with adverse airway health
      effects; however, the underlying mechanism in disease initiation is still largely
      unknown. Recently, microRNAs (miRNAs; small noncoding RNAs) have been suggested
      to be important in maintaining the lung in a disease-free state through
      regulation of gene expression. Although many studies have shown aberrant miRNA
      expression patterns in diseased versus healthy tissue, little is known regarding
      whether environmental agents can induce such changes. OBJECTIVES: We used diesel
      exhaust particles (DEP), the largest source of emitted airborne PM, to
      investigate pollutant-induced changes in miRNA expression in airway epithelial
      cells. We hypothesized that DEP exposure can lead to disruption of normal miRNA
      expression patterns, representing a plausible novel mechanism through which DEP
      can mediate disease initiation. METHODS: Human bronchial epithelial cells were
      grown at air-liquid interface until they reached mucociliary differentiation.
      After treating the cells with 10 microg/cm(2) DEP for 24 hr, we analyzed total
      RNA for miRNA expression using microarray profile analysis and quantitative real
      time polymerase chain reaction. RESULTS: DEP exposure changed the miRNA
      expression profile in human airway epithelial cells. Specifically, 197 of 313
      detectable miRNAs (62.9%) were either up-regulated or down-regulated by 1.5-fold.
      Molecular network analysis of putative targets of the 12 most altered miRNAs
      indicated that DEP exposure is associated with inflammatory responses pathways
      and a strong tumorigenic disease signature. CONCLUSIONS: Alteration of miRNA
      expression profiles by environmental pollutants such as DEP can modify cellular
      processes by regulation of gene expression, which may lead to disease
      pathogenesis.

PMID- 20049128
TI  - Healthy neighborhoods: walkability and air pollution.
AB  - BACKGROUND: The built environment may influence health in part through the
      promotion of physical activity and exposure to pollution. To date, no studies
      have explored interactions between neighborhood walkability and air pollution
      exposure. METHODS: We estimated concentrations of nitric oxide (NO), a marker for
      direct vehicle emissions), and ozone (O(3)) and a neighborhood walkability score,
      for 49,702 (89% of total) postal codes in Vancouver, British Columbia, Canada. NO
      concentrations were estimated from a land-use regression model, O(3) was
      estimated from ambient monitoring data; walkability was calculated based on
      geographic attributes such as land-use mix, street connectivity, and residential
      density. RESULTS: All three attributes exhibit an urban-rural gradient, with high
      walkability and NO concentrations, and low O(3) concentrations, near the city
      center. Lower-income areas tend to have higher NO concentrations and walkability
      and lower O(3) concentrations. Higher-income areas tend to have lower pollution
      (NO and O(3)). "Sweet-spot" neighborhoods (low pollution, high walkability) are
      generally located near but not at the city center and are almost exclusively
      higher income. POLICY IMPLICATIONS: Increased concentration of activities in
      urban settings yields both health costs and benefits. Our research identifies
      neighborhoods that do especially well (and especially poorly) for walkability and
      air pollution exposure. Work is needed to ensure that the poor do not bear an
      undue burden of urban air pollution and that neighborhoods designed for walking,
      bicycling, or mass transit do not adversely affect resident's exposure to air
      pollution. Analyses presented here could be replicated in other cities and
      tracked over time to better understand interactions among neighborhood
      walkability, air pollution exposure, and income level.

PMID- 20049129
TI  - Longitudinal mercury monitoring within the Japanese and Korean communities
      (United States): implications for exposure determination and public health
      protection.
AB  - BACKGROUND: Estimates of exposure to toxicants are predominantly obtained from
      single time-point data. Fish consumption guidance based on these data may be
      incomplete, as recommendations are unlikely to consider impact from factors such
      as intraindividual variability, seasonal differences in consumption behavior, and
      species consumed. OBJECTIVES/METHODS: We studied populations of Korean (n = 108)
      and Japanese (n = 106) women living in the Puget Sound area in Washington State
      to estimate mercury exposure based on fish intake and hair Hg levels at two and
      three time points, respectively. Our goals were to examine changes in hair Hg
      levels, fish intake behavior, and Hg body burden over time; and to determine if
      data from multiple time points could improve guidance. RESULTS/CONCLUSION: More
      than 50 fish species were consumed, with eight species representing approximately
      three-fourths of fish consumed by the Japanese and 10 species representing
      approximately four-fifths of fish intake by the Koreans. Fish species responsible
      for most Hg intake did not change over time; < 10 species accounted for most of
      the Hg body burden in each population. Longitudinal variability of hair Hg levels
      changed slowly across the study period. Japanese with hair Hg levels > 1.2 ppm
      (mean, 2.2 ppm) consumed approximately 150% more fish than those with levels < or
      = 1.2 ppm (mean, 0.7 ppm). However, because many participants consumed
      substantial amounts of fish while having hair-Hg levels < or = 1.2 ppm, the
      nutritional benefits offered from fish consumption should be obtainable without
      exceeding the RfD. We observed a 100% difference in fish intake between open
      ended and 2-week recall fish consumption surveys. Open-ended survey data better
      represent Hg intake as determined from hair Hg levels. Single time-point fish
      intake data appear to be adequate for deriving guidance, but caution is
      warranted, as study is required to determine the significance of the different
      outcomes observed using the two survey time frames.

PMID- 20049130
TI  - Black carbon exposure, oxidative stress genes, and blood pressure in a repeated
      measures study.
AB  - BACKGROUND: Particulate matter (PM) air pollution has been associated with
      cardiovascular morbidity and mortality, and elevated blood pressure (BP) is a
      known risk factor for cardiovascular disease. A small number of studies have
      investigated the relationship between PM and BP and found mixed results. Evidence
      suggests that traffic-related air pollution contributes significantly to PM
      related cardiovascular effects. OBJECTIVES: We hypothesized that black carbon
      (BC), a traffic-related combustion by-product, would be more strongly associated
      with BP than would fine PM [aerodynamic diameter < or = 2.5 microm (PM(2.5))], a
      heterogeneous PM mixture, and that these effects would be larger among
      participants with genetic variants associated with impaired antioxidative
      defense. METHODS: We performed a repeated-measures analysis in elderly men to
      analyze associations between PM(2.5) and BC exposure and BP using mixed-effects
      models with random intercepts, adjusting for potential confounders. We also
      examined statistical interaction between BC and genetic variants related to
      oxidative stress defense: GSTM1, GSTP1, GSTT1, NQO1, catalase, and HMOX-1.
      RESULTS: A 1-SD increase in BC concentration was associated with a 1.5-mmHg
      increase in systolic BP [95% confidence interval (CI), 0.1-2.8] and a 0.9-mmHg
      increase in diastolic BP (95% CI, 0.2-1.6). We observed no evidence of
      statistical interaction between BC and any of the genetic variants examined and
      found no association between PM(2.5) and BP. CONCLUSIONS: We observed positive
      associations between BP and BC, but not between BP and PM(2.5), and found no
      evidence of effect modification of the association between BC and BP by gene
      variants related to antioxidative defense.

PMID- 20049131
TI  - Association between local traffic-generated air pollution and preeclampsia and
      preterm delivery in the south coast air basin of California.
AB  - BACKGROUND: Preeclampsia is a major complication of pregnancy that can lead to
      substantial maternal and perinatal morbidity, mortality, and preterm birth.
      Increasing evidence suggests that air pollution adversely affects pregnancy
      outcomes. Yet few studies have examined how local traffic-generated emissions
      affect preeclampsia in addition to preterm birth. OBJECTIVES: We examined effects
      of residential exposure to local traffic-generated air pollution on preeclampsia
      and preterm delivery (PTD). METHODS: We identified 81,186 singleton birth records
      from four hospitals (1997-2006) in Los Angeles and Orange Counties, California
      (USA). We used a line-source dispersion model (CALINE4) to estimate individual
      exposure to local traffic-generated nitrogen oxides (NO(x)) and particulate
      matter < 2.5 mum in aerodynamic diameter (PM(2.5)) across the entire pregnancy.
      We used logistic regression to estimate effects of air pollution exposures on
      preeclampsia, PTD (gestational age < 37 weeks), moderate PTD (MPTD; gestational
      age < 35 weeks), and very PTD (VPTD; gestational age < 30 weeks). RESULTS: We
      observed elevated risks for preeclampsia and preterm birth from maternal exposure
      to local traffic-generated NO(x) and PM(2.5). The risk of preeclampsia increased
      33% [odds ratio (OR) = 1.33; 95% confidence interval (CI), 1.18-1.49] and 42% (OR
      = 1.42; 95% CI, 1.26-1.59) for the highest NO(x) and PM(2.5) exposure quartiles,
      respectively. The risk of VPTD increased 128% (OR = 2.28; 95% CI, 2.15-2.42) and
      81% (OR = 1.81; 95% CI, 1.71-1.92) for women in the highest NO(x) and PM(2.5)
      exposure quartiles, respectively. CONCLUSION: Exposure to local traffic-generated
      air pollution during pregnancy increases the risk of preeclampsia and preterm
      birth in Southern California women. These results provide further evidence that
      air pollution is associated with adverse reproductive outcomes.

PMID- 20049132
TI  - Air pollution, aeroallergens, and emergency room visits for acute respiratory
      diseases and gastroenteric disorders among young children in six Italian cities.
AB  - BACKGROUND: Past studies reported evidence of associations between air pollution
      and respiratory symptoms and morbidity for children. Few studies examined
      associations between air pollution and emergency room (ER) visits for wheezing,
      and even fewer for gastroenteric illness. We conducted a multicity analysis of
      the relationship between air pollution and ER visits for wheezing and
      gastroenteric disorder in children 0-2 years of age. METHODS: We obtained ER
      visit records for wheezing and gastroenteric disorder from six Italian cities. A
      city-specific case-crossover analysis was applied to estimate effects of
      particulate matter (PM), nitrogen dioxide, sulfur dioxide, ozone, and carbon
      monoxide, adjusting for immediate and delayed effects of temperature. Lagged
      effects of air pollutants up to 6 prior days were examined. The city-specific
      results were combined using a random-effect meta-analysis. RESULTS: CO and SO(2)
      were most strongly associated with wheezing, with a 2.7% increase [95% confidence
      interval (CI), 0.5-4.9] for a 1.04-microg/m(3) increase in 7-day average CO and a
      3.4% (95% CI, 1.5-5.3) increase for an 8.0-microg/m(3) increase in SO(2).
      Positive associations were also found for PM with aerodynamic diameter < or = 10
      microg and NO(2). We found a significant association between the 3-day moving
      average CO and gastroenteric disorders [3.8% increase (95% CI, 1.0-6.8)]. When
      data were stratified by season, the associations were stronger in summer for
      wheezing and in winter for gastroenteric disorders. CONCLUSION: Air pollution is
      associated with triggering of wheezing and gastroenteric disorders in children 0
      2 years of age; more work is needed to understand the mechanisms to help prevent
      wheezing in children.

PMID- 20049133
TI  - Anogenital distance from birth to 2 years: a population study.
AB  - BACKGROUND: Anogenital distance (AGD) is sexually dimorphic in rodents and
      humans, being 2- to 2.5-fold greater in males. It is a reliable marker of
      androgen and antiandrogen effects in rodent reproductive toxicologic studies.
      Data on AGD in humans are sparse, with no longitudinal data collected during
      infancy. OBJECTIVE: This study was designed to determine AGD from birth to 2
      years in males and females and relate this to other anthropometric measures.
      MATERIALS AND METHODS: Infants were recruited from the Cambridge Baby Growth
      Study. AGD was measured from the center of the anus to the base of the scrotum in
      males and to the posterior fourchette in females. Measurements were performed at
      birth and at 3, 12, 18, and 24 months of age. RESULTS: Data included 2,168
      longitudinal AGD measurements from 463 male and 426 female full-term infants
      (median = 2 measurements per infant). Mean AGD (+/- SD) at birth was 19.8 +/- 6.1
      mm in males and 9.1 +/- 2.8 mm in females (p < 0.0001). AGD increased up to 12
      months in both sexes and in a sex-dimorphic pattern. AGD was positively
      correlated with penile length at birth (r = 0.18, p = 0.003) and the increase in
      AGD from birth to 3 months was correlated with penile growth (r = 0.20, p =
      0.001). CONCLUSION: We report novel, longitudinal data for AGD during infancy in
      a large U.K. birth cohort. AGD was sex dimorphic at all ages studied. The
      availability of normative data provides a means of utilizing this biological
      marker of androgen action in population studies of the effects of environmental
      chemicals on genital development.

PMID- 20049134
TI  - Self-reported truck traffic on the street of residence and symptoms of asthma and
      allergic disease: a global relationship in ISAAC phase 3.
AB  - BACKGROUND: Associations between traffic pollution on the street of residence and
      a range of respiratory and allergic outcomes in children have been reported in
      developed countries, but little is known about such associations in developing
      countries. METHODS: The third phase of the International Study of Asthma and
      Allergies in Childhood (ISAAC) was carried out in 13- to 14-year-old and 6- to 7
      year-old children across the world. A question about frequency of truck traffic
      on the street of residence was included in an additional questionnaire. We
      investigated the association between self-reported truck traffic on the street of
      residence and symptoms of asthma, rhinoconjunctivitis, and eczema with logistic
      regression. Adjustments were made for sex, region of the world, language, gross
      national income, and 10 other subject-specific covariates. RESULTS: Frequency of
      truck traffic on the street of residence was positively associated with the
      prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema with an
      exposure-response relationship. Odds ratios (95% confidence intervals) for
      "current wheeze" and "almost the whole day" versus "never" truck traffic were
      1.35 (1.23-1.49) for 13- to 14-year-olds and 1.35 (1.22-1.48) for 6- to 7-year
      olds. CONCLUSIONS: Higher exposure to self-reported truck traffic on the street
      of residence is associated with increased reports of symptoms of asthma,
      rhinitis, and eczema in many locations in the world. These findings require
      further investigation in view of increasing exposure of the world's children to
      traffic.

PMID- 20049135
TI  - Recent insights into the mechanisms of vasospastic angina.
AB  - Coronary artery spasm plays an important role in the pathogenesis of many types
      of ischemic heart disease, not only in vasospastic angina but also in myocardial
      infarction and sudden death, particularly in the asian population. Patients with
      vasospastic angina are known to have defective endothelial function due to
      reduced nitric oxide bioavailability. Moreover, markers of oxidative stress and
      plasma levels of C-reactive protein are elevated. Smoking, polymorphysms of
      endothelial nitric oxide synthetase (eNOS), and low-grade inflammation have been
      regarded as the most important risk factors for vasospastic angina. The recent
      body of evidence indicates that RhoA and its down stream effector, ROCK/Rho
      kinase, are associated with hypercontraction of vascular smooth muscle of the
      coronary artery and regulation of eNOS activity. Thus, endothelial dysfunction
      through abnormalities of eNOS and enhanced contractility of vascular smooth
      muscle in coronary artery segments are considered major mechanisms in vasospastic
      angina. However, the precise mechanisms for coronary vasospasm are not well
      understood. This article will review current understanding of the mechanism of
      coronary artery spasm.

PMID- 20049136
TI  - The significance of clopidogrel low-responsiveness on stent thrombosis and
      cardiac death assessed by the verifynow p(2)y(12) assay in patients with acute
      coronary syndrome within 6 months after drug-eluting stent implantation.
AB  - BACKGROUND AND OBJECTIVES: Clopidogrel resistance or low-responsiveness may be
      associated with recurrent atherothrombotic events after drug-eluting stent (DES)
      implantation. We prospectively evaluated the association between clopidogrel
      resistance assessed by the Verifynow P(2)Y(12) assay (Accumetrics, San Diego, CA,
      USA) and stent thrombosis (ST) or cardiac death (CD) in patients with acute
      coronary syndrome (ACS) within 6 months after DES implantation. SUBJECTS AND
      METHODS: We enrolled 237 consecutive patients (160 males, 65.2+/-10.3 years) with
      ACS who received a DES implantation. The composite endpoint was defined to CD or
      ST by Academic Research Consortium definitions within 6 months post-implantation.
      Clopidogrel resistance was defined as <20% inhibition of the P(2)Y(12) receptor.
      RESULTS: Baseline demographic characteristics were similar between 142 normal
      individuals and 95 clopidogrel resistant patients. CD occurred in one case (0.7%)
      in the normal group and two cases (2.13%) in the resistant group (p=0.344). There
      was no episode of ST in the normal group and four episodes in the resistant group
      (4.2%, four definite ST) (p=0.035). Univariate logistic regression revealed an
      adjusted odds ratio (OR) for composite end point of CD or ST of 9.646 {95%
      confidence interval (CI) 1.139-81.679}, and multivariate logistic regression for
      composite end point revealed an OR of 12.074 (95% CI 1.205-120.992). CONCLUSION:
      Clopidogrel low-responsiveness assessed by the Verifynow P(2)Y(12) assay is an
      independent predictor of ST and composite end point of ST or CD in patients with
      ACS within 6 months after DES implantation.

PMID- 20049137
TI  - Relationship between serum biochemical markers of myocardial fibrosis and
      diastolic function at rest and with exercise in hypertrophic cardiomyopathy.
AB  - BACKGROUND AND OBJECTIVES: Recent studies have demonstrated the usefulness of
      biochemical markers of collagen turnover as markers of myocardial fibrosis in
      various diseases. In this study, we hypothesized that increased collagen markers
      in patients with hypertrophic cardiomyopathy (HCM) were correlated with diastolic
      function at rest and diastolic functional reserve during exercise. SUBJECTS AND
      METHODS: Thirty-six patients with HCM and 21 controls with normal left
      ventricular thickness were studied. Mitral septal annular velocities and mitral
      inflow velocities were measured at rest and during graded supine bicycle exercise
      (25 W, 3-minute increments) for the assessment of diastolic function at rest and
      during exercise. By radioimmunoassay, a byproduct of collagen III synthesis
      (PIIINP) and peptides resulting from collagen I synthesis (PINP) and degradation
      (ICTP) were measured. The patients with HCM were divided into two groups
      according to the median value of the PINP/ICTP ratio in the group. RESULTS: At
      rest, the mitral annular early diastolic velocity (E') was lower and the E/E' was
      higher in the patients with HCM with high a PINP/ICTP ratio compared with
      patients with HCM with a low PINP/ICTP ratio and controls (p<0.001, p=0.012).
      With exercise, the Doppler parameters were increased in all groups, but there was
      no significant difference in the change in E' and E/E' during exercise according
      to collagen turnover markers. CONCLUSION: A higher PINP/ICTP ratio was associated
      with resting diastolic dysfunction in patients with HCM; however, there was no
      relationship with augmented diastolic dysfunction during exercise. We suggest
      that the type I collagen synthesis-to-degradation ratio is a useful marker of
      resting diastolic function in patients with HCM.

PMID- 20049138
TI  - Simple method of counterclockwise isthmus conduction block by comparing double
      potentials and flutter cycle length.
AB  - BACKGROUND AND OBJECTIVES: Local wide split double potentials are used as a
      parameter to determine complete conduction block during cavotricuspid isthmus
      ablation in patients with isthmus dependent atrial flutter. However, delayed slow
      conduction in that region can sometimes be very difficult to differentiate from
      complete block. Flutter cycle length (FCL) can be used to confirm isthmus
      conduction block, because FCL is a measure of conduction time around the
      tricuspid annulus (TA). This study was designed to determine which degree of
      splitting of the local electrograms is adequate to confirm complete isthmus
      block, using FCL as a reference. SUBJECTS AND METHODS: Cavotricuspid isthmus
      (CTI) ablation was performed in fifty consecutive patients. The interval between
      the pacing stimulus on the lateral side of the CTI and the first component of the
      double potentials on the block line (SD1) corresponded to the counterclockwise
      conduction time. The interval between the pacing stimulus and second component
      (SD2) represented the clockwise conduction time to the contralateral side of the
      ablation line. SD1 and SD2 were measured before and after complete isthmus block.
      RESULTS: An SD1+SD2 reaching 90% of the FCL identified the counterclockwise
      isthmus conduction block with 94% sensitivity and 100% specificity. CONCLUSION:
      If the sum of SD1 and SD2 following isthmus ablation was close to the FCL,
      complete conduction block was predicted with high diagnostic accuracy and
      positive predictive value for at least counterclockwise conduction.

PMID- 20049139
TI  - Characteristics of myocardial deformation and rotation in subjects with diastolic
      dysfunction without diastolic heart failure.
AB  - BACKGROUND AND OBJECTIVES: There have been very few pathophysiologic studies on
      isolated diastolic dysfunction. We hypothesized that the characteristics of
      isolated diastolic dysfunction would be located, on the clinical continuum,
      between those of a normal heart and diastolic heart failure. SUBJECTS AND
      METHODS: We enrolled 102 subjects who had no history of overt symptoms of heart
      failure and who had a left ventricular ejection fraction of more than 50%. They
      were examined for myocardial deformation and rotation using the two-dimensional
      speckle tracking image (2D-STI) technique. RESULTS: The circumferential strains
      and radial strain at the apical level (RS(apex)) were related to the ratio of the
      transmitral early peak velocity over the early diastolic mitral annulus velocity
      (E/E'). After adjustment for age, the RS(apex) showed a positive relationship
      with the E/E' ratio; whereas, the circumferential strains did not. Instead, the
      circumferential strains demonstrated a significant correlation with age. Basal
      rotation and left ventricular (LV) torsion were also related to age, but had no
      relationship with the E/E' ratio. However, as the E/E' ratio value increased,
      systolic mitral annular velocity decreased. CONCLUSION: Except for the RS(apex),
      LV myocardial deformation and rotation did not vary with the degree of E/E' ratio
      elevation when there was no associated diastolic heart failure. Additionally, in
      clinical situations such as isolated diastolic dysfunction, the advancement of
      age has a relatively greater influence on characteristics of LV myocardial
      deformation and rotation rather than on the E/E' ratio.

PMID- 20049140
TI  - N-terminal pro-B-type natriuretic Peptide in overweight and obese patients with
      and without diabetes: an analysis based on body mass index and left ventricular
      geometry.
AB  - BACKGROUND AND OBJECTIVES: Several recent studies have shown that there is an
      inverse relationship between plasma B-type natriuretic peptide (BNP) and body
      mass index (BMI) in subjects with and without heart failure. Obesity frequently
      coexists with diabetes, so it is important to consider the relationship between
      diabetes and natriuretic peptide levels. We evaluated the influence of diabetes
      on the correlation of BNP and BMI. SUBJECTS AND METHODS: We examined 933 patients
      with chest pain and/or dyspnea undergoing cardiac catheterization between Feb.
      2006 and Nov. 2007 in the Maryknoll cardiac center who had creatinine levels <2.0
      mg/dL and normal systolic heart function. BMI was checked, transthoracic
      echocardiography was performed, and aminoterminal pro-brain natriuretic peptide
      (NT-proBNP) was sampled at the start of each case. RESULTS: In 733 non-diabetic
      patients, mean plasma NT-proBNP levels of non obese individuals (BMI <23
      kg/m(2)), overweight individuals (23</= BMI <25 kg/m(2)), and obese individuals
      (BMI >/=25 kg/m(2)) showed a significant negative correlation with increasing BMI
      (856.39+/-237.3 pg/mL, 601.69+/-159.6 pg/mL, 289.62+/-164.9 pg/mL, respectively,
      p<0.0001). However, in 200 diabetic patients, the correlation between BMI and NT
      proBNP was not significant (r=-0.21, p=0.19), and NT-proBNP did not correlate
      with mitral E/Ea in obese diabetic patients (r=0.14, p=0.56). NT-proBNP was
      significantly correlated with mitral E/Ea in the non-obese (r=0.24, p=0.008) and
      non diabetic (r=0.32, p=0.003) groups. Left ventricular (LV) mass index was
      significantly correlated with NT-proBNP in all BMI groups (r=0.61, p<0.001), and
      patients with concentric cardiac hypertrophy showed the highest NT-proBNP levels.
      CONCLUSION: The present study demonstrates that obese patients have reduced
      concentrations of NT-proBNP compared to non obese patients despite having higher
      LV filling pressures. However, NT-proBNP is not suppressed in obese patients with
      diabetes. This suggests that factors other than cardiac status affect NT-proBNP
      concentrations.

PMID- 20049141
TI  - Eosinophilic endomyocarditis combined with pericardial and pleural effusion.
AB  - Eosinophilic endomyocarditis is a manifestation of hypereosinophilic syndrome,
      characterized by prolonged (>6 months), unexplained peripheral blood eosinophilia
      (>1,500 cells/mm(3)) with end-organ damage in unknown causes. We report a case of
      a 42-year-old patient who developed eosinophilic endomyocarditis following upper
      respiratory tract symptoms for 2 months. Additionally, endomyocarditis was
      combined with massive pleural effusion and pericardial effusion, which have not
      been reported in Korea.

PMID- 20049142
TI  - Hypertension caused by renal arteriovenous fistula.
AB  - We describe a case of secondary hypertension caused by renal arteriovenous
      fistula. An 8-year old girl was hospitalized with a severe headache, vomiting,
      and seizure. Renal angiography demonstrated multiple renal arteriovenous fistula
      and increased blood renin concentration in the left renal vein. Thus, left renal
      arteriovenous fistula and renin induced secondary hypertension were diagnosed.
      Her blood pressure was well controlled by medication with angiotensin converting
      enzyme inhibitor.

PMID- 20049143
TI  - Takayasu's Arteritis Involving the Ostia of Three Large Coronary Arteries.
AB  - Takayasu's arteritis can involve the ostia of coronary arteries. We report a
      patient with Takayasu's arteritis involving the ostia of three large coronary
      arteries who was successfully treated by percutaneous coronary intervention (PCI)
      with a drug-eluting stent (DES) and had a good clinical outcome after 12 months.
      A 37-year-old male with unstable angina was admitted to our cardiovascular
      center. The patient had Takayasu's arteritis and an aortic valve replacement with
      a metallic valve due to severe aortic regurgitation 7 years previously. Coronary
      angiography (CAG) showed a 95% discrete eccentric luminal narrowing at the ostia
      of the large left anterior descending (LAD) and left circumflex (LCX) arteries,
      and a 99% discrete eccentric luminal narrowing at the ostium of the large right
      coronary artery (RCA). The patient was treated with prednisolone for 14 days. Two
      large paclitaxel-eluting stents (PES) were then implanted in the distal left main
      coronary artery using the kissing stent technique. After 6 months, a CAG did not
      reveal restenosis or recurrent coronary artery disease. Thus, PCI with a DES for
      patients with significant coronary involvement secondary to Takayasu's arteritis
      is an effective and an alternative treatment when coronary bypass grafting is not
      option.

PMID- 20049144
TI  - Preparing for a benzodiazepine tsunami.

PMID- 20049145
TI  - Early- versus Late-Onset Dysthymia: A Meaningful Clinical Distinction?
AB  - In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic
      disorder is categorized as either early-onset or late-onset, based upon the
      emergence of symptoms before or after the age of 21, respectively. Does this
      diagnostic distinction have any meaningful clinical implications? In this edition
      of The Interface, we present empirical studies that have, within a single study,
      compared individuals with early-versus late-onset dysthymia. In this review, we
      found that, compared to those with late-onset dysthymia, early-onset patients are
      more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less
      psychological resilience, and have more prominent family loadings for mood
      disorders. These findings suggest that this distinction is meaningful and that
      the early-onset subtype of dysthymia is more difficult to effectively treat.

PMID- 20049146
TI  - The blood brain barrier and the role of cytokines in neuropsychiatry.
AB  - Cytokines have emerged in the past two decades as some of the most extensively
      studied peptide molecules contributing to the pathophysiology of many diseases.
      As a result of these translational efforts, discovery of drugs aimed at reducing
      damage caused by cytokines has been accomplished for some conditions. The
      characterization of the role of cytokines in the pathophysiology of
      neuropsychiatric disorders is still in its infancy. This article highlights the
      growing correlation of brain cytokine levels with corresponding psychiatric
      symptoms, known as cytokine-induced sickness behavior, comprising increased
      sleep, decreased appetite, decreased sexual drive, and overwhelming fatigue
      frequently combined with fever.

PMID- 20049147
TI  - Zonisamide Combined with Cognitive Behavioral Therapy in Binge Eating Disorder: A
      One-year Follow-up Study.
AB  - Objective. Binge eating disorder is a serious, prevalent eating disorder that is
      associated with overweight. Zonisamide is an antiepileptic drug that can promote
      weight loss. We evaluated the efficacy and safety of zonisamide as augmentation
      to individual cognitive behavioral therapy in the treatment of binge eating
      disorder patients. DESIGN: controlled open study. PARTICIPANTS: Twenty four
      threshold and subthreshold binge eating disorder patients were enrolled in the
      cognitive behavioral therapy treatment group, and 28 patients in the cognitive
      behavioral therapy plus zonisamide group. MEASUREMENTS: At the beginning (T0), at
      the end (T1) of treatment, and one year after the end of treatment (T2), body
      mass index was measured and Eating Disorder Examination-Questionnaire, Binge
      Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory were
      administered.Results. At T1 the cognitive behavioral therapy plus zonisamide
      group showed a higher mean reduction of body mass index, Eating Disorder
      Examination-Questionnaire, Beck Depression Inventory, and Binge Eating Scale
      scores. At T2, the cognitive behavior therapy group regained weight, while the
      cognitive behavioral therapy plus zonisamide group reduced their body mass and
      showed a higher reduction in binge eating frequency and Binge Eating Scale,
      Eating Disorder Examination-Questionnaire Restraint, and State and Trait Anxiety
      Inventory scores.Conclusion. The zonisamide augmentation to individual cognitive
      behavior therapy can improve the treatment of binge eating disorder patients,
      reducing body weight and the number of binge eating episodes. These results are
      maintained one year after the end of treatment.

PMID- 20049148
TI  - Are clozapine patients at risk for blood dyscrasias with concomitant tamiflu use?
AB  - Flu vaccination is the best protection against seasonal flu; however, as mutated
      strains of the flu develop and/or unvaccinated people are exposed to the wild
      virus, antiviral prophylaxis becomes more important. High-risk patients, such as
      those institutionalized, are particularly vulnerable to adverse drug events and
      possibly even more so during the course of active viral infection. As clinicians
      pursue antiviral treatment, it is important to know the potential risks of
      prescribing concurrent medication regimens. The objective of this study was to
      contribute to the evolving literature by evaluating the occurrence of blood
      dyscrasias with concurrent use of oseltamivir and clozapine (a drug used to treat
      refractory schizophrenia). This study was a retrospective chart review conducted
      at a 240-bed New York State mental health facility during an influenza outbreak
      where oseltamivir was distributed to the vast majority of inpatients. The records
      of 32 patients treated with concurrent oseltamivir and clozapine were assessed
      for alterations in white blood count and/or absolute neutrophil count at
      designated periods and compared to baseline lab values. A repeated measures ANOVA
      was used to analyze the data. RESULTS: No changes in white blood cell were noted
      as a result of concomitant oseltamivir and clozapine therapy in the study sample;
      however, there were statistically significant differences between the absolute
      neutrophil count from before oseltamivir and the two time periods following
      oseltamivir administration. Cautions are detailed regarding concomitant use;
      however, proactive clozapine discontinuation prior to antiviral treatment is
      unwarranted.

PMID- 20049149
TI  - Cranial Nerves III, IV, and VI: Oculomotor Function.
AB  - Motor activity affecting the direction of gaze, the position of the eyelids, and
      the size of the pupils are served by cranial nerves III, IV, and VI. Unusual
      oculomotor activity is often encountered in psychiatric patients and can be quite
      informative. Evaluation techniques include casual observation and simple tests
      that require no equipment in addition to the sophisticated methods used in
      specialty clinics and research labs. This article reviews pupil size, extraocular
      movements, nystagmus, lid retraction, lid lag, and ptosis. Beyond screening for
      diseases and localizing lesions, these tests yield useful information about the
      individual's higher cortical function, extrapyramidal motor functioning, and
      toxic/pharmacologic state.

PMID- 20049150
TI  - Treatment initiatives for patients with Alzheimer's disease.
AB  - There are several treatment initiatives a psychiatrist should consider when
      treating a patient with Alzheimer's disease. The author discusses five treatment
      initiatives in the order in which they tend to arise during the illness
      progression of a patient with Alzheimer's disease: screening for Alzheimer's
      disease, providing information to patients on nonevidence-based treatments of
      Alzheimer's disease, assisting patients with contacting loved ones as the disease
      progresses, confronting patients with difficult decisions, and discussing moral
      concerns of the patient with his or her loved ones. Case examples and a review of
      literature are also provided.

PMID- 20049151
TI  - Eric R. Kandel: my kind of saint.

PMID- 20049152
TI  - Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor.
AB  - Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor
      (ACT). We report an infant with Cushing syndrome due to adrenocortical carcinoma.
      The patient presented at six months of age with a three-month history of growth
      failure, rapid weight gain, acne, and irritability. Physical examination showed
      obesity, hypertension, and Cushingoid features. Biochemical evaluation showed
      very high serum cortisol, mildly elevated testosterone, and suppressed ACTH.
      Abdominal MRI revealed a heterogeneous right adrenal mass extending into the
      inferior vena cava. Evaluation for metastases was negative. The tumor was removed
      surgically en bloc. Pathologic examination demonstrated low mitotic rate, but
      capsular and vascular invasion. She received no adjuvant therapy. Her linear
      growth has improved and Cushingoid features resolved. Hormonal markers and
      quarterly PET scans have been negative for recurrence 24 months postoperatively.
      In conclusion, adrenocortical neoplasms in children are rare, but should be
      considered in the differential diagnosis of Cushing syndrome.

PMID- 20049154
TI  - Comparison between Actual and Perceived Height of Parents of Children with Short
      Stature and Controls.
AB  - Objectives. We investigate whether parents complaining of their children's short
      stature have misconception of their height. Methods. Parents were asked to report
      their own height and were then measured. We compared the difference between
      reported and actual height of parents of children with short stature (CSS) with
      that of parents coming for a well child care visit (WCC) and parents of children
      referred to the endocrinologist without short stature (Endo). The accuracy of
      reported height from short (below 25%) and tall (above 75%) parents was compared.
      Results. The CSS fathers were shorter than WCC (P < .01) fathers. The CSS mothers
      were shorter than the Endo (P < .01) and WCC (P < .001) mothers. There was no
      difference between reported and actual height when comparing the groups based on
      the reason for the visit or based on the parental height. Conclusions. Parents of
      CSS and short parents do not have a misconception of their height.

PMID- 20049153
TI  - Breast milk hormones and their protective effect on obesity.
AB  - Data accumulated over recent years have significantly advanced our understanding
      of growth factors, cytokines, and hormones in breast milk. Here we deal with
      leptin, adiponectin, IGF-I, ghrelin, and the more recently discovered hormones,
      obestatin, and resistin, which are present in breast milk and involved in food
      intake regulation and energy balance. Little is known about these compounds in
      infant milk formulas. Nutrition in infancy has been implicated in the long-term
      tendency to obesity, and a longer duration of breastfeeding appears to protect
      against its development. Diet-related differences in serum leptin and ghrelin
      values in infancy might explain anthropometric differences and differences in
      dietary habits between breast-fed and formula-fed infants also later in life.
      However, there are still gaps in our understanding of how hormones present in
      breast milk affect children. Here we examine the data related to hormones
      contained in mother's milk and their potential protective effect on subsequent
      obesity.

PMID- 20049155
TI  - Mammary Fat Can Adjust Prolactin Effect on Mammary Epithelial Cells via Leptin
      and Estrogen.
AB  - Leptin, like estrogen, is one of the endo/paracrine factors, which are
      synthesized in and secreted from mature adipocytes. The roles of the mammary fat
      pad and mammary adipocytes in the initiation of lactation are not clear. In this
      study, we showed that combination of prolactin, leptin and estrogen elevated the
      expression of the milk protein beta-lactoglobulin. We also showed that after
      prolactin stimulate the secretion of leptin from the mammary fat, leptin
      upregulated the expression of estrogen receptor alpha in the mammary epithelial
      cells. Also, prolactin affected aromatase mRNA expression in the bovine mammary
      fat and we demonstrated that leptin and prolactin can affect cholesterol
      secretion from explants in culture to the medium. Therefore, we suggest that
      prolactin initiates estrogen expression (as represented by aromatase mRNA) in the
      mammary fat pad, whereas leptin stimulates estrogen receptor alpha expression in
      the mammary epithelial cells. We hypothesize that leptin and estrogen, secreted
      from the mammary fat regulate lactation after stimulation of prolactin.

PMID- 20049156
TI  - Circulating 25-hydroxyvitamin d levels in fully breastfed infants on oral vitamin
      d supplementation.
AB  - Objective. To examine the effectiveness of oral vitamin D(3) (400 IU)
      supplementation on the nutritional vitamin D status of breastfeeding infants.
      Design. As part of a larger ongoing vitamin D RCT trial of lactating women,
      infants of mothers assigned to control received 1 drop of 400 IU vitamin D(3)/day
      starting at one month of age. Infant 25(OH)D levels (mean +/- S.D.) were measured
      by RIA at visits 1, 4, and 7. Results. The infant mean +/- S.D. 25(OH)D at
      baseline was 16.0 +/-9.3 ng/mL (range 1.0-40.8; n = 33); 24 (72.7%) had baseline
      levels <20 ng/mL (consistent with deficiency). The mean levels increased to 43.6
      +/-14.1 (range 18.2-69.7) at 4 months and remained relatively unchanged at month
      7: 42.5 +/-12.1 ng/mL (range 18.9-67.2). The change in values between 1 and 4
      months and 1 and 7 months was statistically significant (P </= .0001), and
      despite a decrease in dose per kilogram, values were not significantly different
      between months 4 and 7 (P = .66). Conclusions. Oral vitamin D(3) supplementation
      as an oil emulsion was associated with significant and sustained increases in
      25(OH)D from baseline in fully breastfeeding infants through 7 months.

PMID- 20049157
TI  - Does vitamin d deficiency cause hypertension? Current evidence from clinical
      studies and potential mechanisms.
AB  - Vitamin D deficiency is widely prevalent across all ages, races, geographical
      regions, and socioeconomic strata. In addition to its important role in skeletal
      development and calcium homeostasis, several recent studies suggest its
      association with diabetes, hypertension, cardiovascular disease, certain types of
      malignancy, and immunologic dysfunction. Here, we review the current evidence
      regarding an association between vitamin D deficiency and hypertension in
      clinical and epidemiological studies. We also look into plausible biological
      explanations for such an association with the renin-angiotensin-aldosterone
      system and insulin resistance playing potential roles. Taken together, it appears
      that more studies in more homogeneous study populations are needed before a firm
      conclusion can be reached as to whether vitamin D deficiency causes or aggravates
      hypertension and whether vitamin D supplementation is safe and exerts
      cardioprotective effects. The potential problems with bias and confounding
      factors present in previous epidemiological studies may be overcome or minimized
      by well designed randomized controlled trials in the future.

PMID- 20049158
TI  - Gender Differences in the Association between Sleep Duration and Body
      Composition: The Cardia Study.
AB  - Sleep duration has been inversely associated with body mass index (BMI). We
      examined the relationship between self-reported sleep duration and BMI, waist
      circumference, and percent body fat in Black and White individuals from the
      CARDIA study. Box-Tidwell regression models were adjusted for age and race (Model
      1), additional lifestyle and demographic variables (Model 2), and physical
      activity (Model 3). There were significant interactions between sleep and gender
      for the main outcome variables. In men, there was a trend for an inverse
      relationship between reported sleep duration and BMI in Model 2 (beta = -0.20, P
      = .053) but not model 3 (beta = -0.139, P = .191). In women, inverse
      relationships were observed between sleep duration and BMI (beta = -0.294, P =
      .005) and waist circumference (beta = -0.442, P = .059), in Model 2. These
      associations became nonsignificant in model 3 (BMI: beta = -0.172, P = .084;
      waist circumference: beta = -0.161, P = .474). Our results are consistent with
      previous findings that sleep is associated with BMI and other body composition
      variables. However, the relationship between self-reported sleep duration and
      body composition may be stronger in women than in men.

PMID- 20049159
TI  - Vitamin d pathway genes, diet, and risk of renal cell carcinoma.
AB  - Mediated by binding to the high-affinity vitamin D receptor (VDR), vitamin D
      forms a heterodimer complex with the retinoid-X-receptor (RXR). Variation in both
      genes has been shown to modify renal cell carcinoma (RCC) risk. Therefore, we
      investigated whether VDR and RXRA polymorphisms modify associations between RCC
      risk and frequency of dietary intake of vitamin D and calcium rich foods, and
      occupational ultraviolet exposure among 777 RCC case and 1035 controls from
      Central and Eastern Europe. A positive association was observed in this
      population between increasing dietary intake frequency of yogurt, while an
      inverse association was observed with egg intake frequency. RXRA polymorphisms,
      located 3' of the coding sequence, modified associations between specific vitamin
      D rich foods and RCC risk, while RXRA polymorphisms, located in introns 1 and 4,
      modified associations with specific calcium rich foods. Results suggest that
      variants in the RXRA gene modified the associations observed between RCC risk and
      calcium and vitamin D intake.

PMID- 20049160
TI  - iFlow: A Graphical User Interface for Flow Cytometry Tools in Bioconductor.
AB  - Flow cytometry (FCM) has become an important analysis technology in health care
      and medical research, but the large volume of data produced by modern high
      throughput experiments has presented significant new challenges for computational
      analysis tools. The development of an FCM software suite in Bioconductor
      represents one approach to overcome these challenges. In the spirit of the R
      programming language (Tree Star Inc., "FlowJo," http://www.owjo.com), these tools
      are predominantly console-driven, allowing for programmatic access and rapid
      development of novel algorithms. Using this software requires a solid
      understanding of programming concepts and of the R language. However, some of
      these tools|in particular the statistical graphics and novel analytical
      methods|are also useful for nonprogrammers. To this end, we have developed an
      open source, extensible graphical user interface (GUI) iFlow, which sits on top
      of the Bioconductor backbone, enabling basic analyses by means of convenient
      graphical menus and wizards. We envision iFlow to be easily extensible in order
      to quickly integrate novel methodological developments.

PMID- 20049161
TI  - Merging mixture components for cell population identification in flow cytometry.
AB  - We present a framework for the identification of cell subpopulations in flow
      cytometry data based on merging mixture components using the flowClust
      methodology. We show that the cluster merging algorithm under our framework
      improves model fit and provides a better estimate of the number of distinct cell
      subpopulations than either Gaussian mixture models or flowClust, especially for
      complicated flow cytometry data distributions. Our framework allows the automated
      selection of the number of distinct cell subpopulations and we are able to
      identify cases where the algorithm fails, thus making it suitable for application
      in a high throughput FCM analysis pipeline. Furthermore, we demonstrate a method
      for summarizing complex merged cell subpopulations in a simple manner that
      integrates with the existing flowClust framework and enables downstream data
      analysis. We demonstrate the performance of our framework on simulated and real
      FCM data. The software is available in the flowMerge package through the
      Bioconductor project.

PMID- 20049162
TI  - Fluorescence intensity normalisation: correcting for time effects in large-scale
      flow cytometric analysis.
AB  - A next step to interpret the findings generated by genome-wide association
      studies is to associate molecular quantitative traits with disease-associated
      alleles. To this end, researchers are linking disease risk alleles with gene
      expression quantitative trait loci (eQTL). However, gene expression at the mRNA
      level is only an intermediate trait and flow cytometry analysis can provide more
      downstream and biologically valuable protein level information in multiple cell
      subsets simultaneously using freshly obtained samples. Because the throughput of
      flow cytometry is currently limited, experiments may need to span over several
      weeks or months to obtain a sufficient sample size to demonstrate genetic
      association. Therefore, normalisation methods are needed to control for technical
      variability and compare flow cytometry data over an extended period of time. We
      show how the use of normalising fluorospheres improves the repeatability of a
      cell surface CD25-APC mean fluorescence intensity phenotype on CD4(+) memory T
      cells. We investigate two types of normalising beads: broad spectrum and spectrum
      matched. Lastly, we propose two alternative normalisation procedures that are
      usable in the absence of normalising beads.

PMID- 20049164
TI  - Assessing the quality of whole genome alignments in bacteria.
AB  - Comparing genomes is an essential preliminary step to solve many problems in
      biology. Matching long similar segments between two genomes is a precondition for
      their evolutionary, genetic, and genome rearrangement analyses. Though various
      comparison methods have been developed in recent years, a quantitative assessment
      of their performance is lacking. Here, we describe two families of assessment
      measures whose purpose is to evaluate bacteria-oriented comparison tools. The
      first measure is based on how well the genome segmentation fits the gene
      annotation of the studied organisms; the second uses the number of segments
      created by the segmentation and the percentage of the two genomes that are
      conserved. The effectiveness of the two measures is demonstrated by applying them
      to the results of genome comparison tools obtained on 41 pairs of bacterial
      species. Despite the difference in the nature of the two types of measurements,
      both show consistent results, providing insights into the subtle differences
      between the mapping tools.

PMID- 20049163
TI  - A survey of flow cytometry data analysis methods.
AB  - Flow cytometry (FCM) is widely used in health research and in treatment for a
      variety of tasks, such as in the diagnosis and monitoring of leukemia and
      lymphoma patients, providing the counts of helper-T lymphocytes needed to monitor
      the course and treatment of HIV infection, the evaluation of peripheral blood
      hematopoietic stem cell grafts, and many other diseases. In practice, FCM data
      analysis is performed manually, a process that requires an inordinate amount of
      time and is error-prone, nonreproducible, nonstandardized, and not open for re
      evaluation, making it the most limiting aspect of this technology. This paper
      reviews state-of-the-art FCM data analysis approaches using a framework
      introduced to report each of the components in a data analysis pipeline. Current
      challenges and possible future directions in developing fully automated FCM data
      analysis tools are also outlined.

PMID- 20049165
TI  - The potential to forgo social welfare gains through overrelianceon cost
      effectiveness/cost utility analyses in the evidence base for public health.
AB  - Economic evaluations of clinical treatments most commonly take the form of cost
      effectiveness or cost utility analyses. This is appropriate since the main
      sometimes the only-benefit of such interventions is increased health. The
      majority of economic evaluations in public health, however, have also been
      assessed using these techniques when arguably cost benefit analyses would in many
      cases have been more appropriate, given its ability to take account of nonhealth
      benefits as well. An examination of the nonhealth benefits from a sample of
      studies featured in a recent review of economic evaluations in public health
      illustrates how overfocusing on cost effectiveness/cost utility analyses may lead
      to forgoing potential social welfare gains from programmes in public health.
      Prior to evaluation, programmes should be considered in terms of the potential
      importance of nonhealth benefits and where these are considerable would be better
      evaluated by more inclusive economic evaluation techniques.

PMID- 20049166
TI  - Myelofibrosis-associated lymphoproliferative disease: retrospective study of 16
      cases and literature review.
AB  - Background. To better describe the clinical, biological, and the outcome of non
      Hodgkin's lymphoma (NHL) with, at the initial presentation, bone marrow fibrosis
      (MF). Patients and Methods. From January 2001 to January 2007, 16 eligible
      patients with NHL and MF were retrieved from the Pathology Department of the
      University hospital of Amiens. Median age of patients was 62 years (range 16-74)
      with a sex ratio male/female of 3. Results. MF is associated with all types of
      lymphoma predominantly with B-cell phenotype and it seems to be more associated
      with low-grade NHL. B-symptoms are more frequent at diagnosis and more patients
      presented with an elevated LDH level. JAK-2 was negative in the 10 patients
      analysed. Two patients presented with features of primary MF with no evidence of
      lymphoma. Overall response rate was 94% after the first line of therapy with
      regression or improvement of MF. Relapse occurred in 8 patients (47%) with
      recurrence of MF in all of them. After a median follow-up of 42 months, 12
      patients were alive with an overall survival rate for the entire group of 75%.
      Conclusions. MF-associated NHL is a rare manifestation which may be associated
      with all types of NHL and its presence does not seem to confer a poor prognosis.
      A search for lymphoproliferation should be considered when the cause of MF is not
      apparent.

PMID- 20049167
TI  - A critical assessment of geographic clusters of breast and lung cancer incidences
      among residents living near the Tittabawassee and Saginaw Rivers, Michigan, USA.
AB  - OBJECTIVES: To assess previously determined geographic clusters of breast and
      lung cancer incidences among residents living near the Tittabawassee and Saginaw
      Rivers, Michigan, using a new set of environmental factors. MATERIALS AND
      METHODS: Breast and lung cancer data were acquired from the Michigan Department
      of Community Health, along with point source pollution data from the U.S.
      Environmental Protection Agency. The datasets were used to determine whether
      there is a spatial association between disease risk and environmental
      contamination. GIS and spatial techniques were combined with statistical analysis
      to investigate local risk of breast and lung cancer. RESULTS AND CONCLUSION: The
      study suggests that neighborhoods in close proximity to the river were associated
      with a high risk of breast cancer, while increased risk of lung cancer was
      detected among neighborhoods in close proximity to point source pollution and
      major highways. Statistically significant (P </= .001) clusters of cancer
      incidences were observed among residents living near the rivers. These findings
      are useful to researchers and governmental agencies for risk assessment,
      regulation, and control of environmental contamination in the floodplains.

PMID- 20049168
TI  - Circulating tumor cell analysis: technical and statistical considerations for
      application to the clinic.
AB  - Solid cancers are a leading cause of death worldwide, primarily due to the
      failure of effective clinical detection and treatment of metastatic disease in
      distant sites. There is growing evidence that the presence of circulating tumor
      cells (CTCs) in the blood of cancer patients may be an important indicator of the
      potential for metastatic disease and poor prognosis. Technological advances have
      now facilitated the enumeration and characterization of CTCs using methods such
      as PCR, flow cytometry, image-based immunologic approaches, immunomagnetic
      techniques, and microchip technology. However, the rare nature of these cells
      requires that very sensitive and robust detection/enumeration methods be
      developed and validated in order to implement CTC analysis for widespread use in
      the clinic. This review will focus on the important technical and statistical
      considerations that must be taken into account when designing and implementing
      CTC assays, as well as the subsequent interpretation of these results for the
      purposes of clinical decision making.

PMID- 20049169
TI  - Successful surgical resection for peritoneal implantation of hepatocellular
      carcinoma at the paracardial portion.
AB  - Peritoneal implantation from hepatocellular carcinoma has been rarely reported.
      It may occur at various sites. Here we present a surgically resected case of
      peritoneal implantation to the diaphragm from hepatocellular carcinoma. A 50-year
      old woman underwent right hemihepatectomy extended to a medial part of Couinaud
      segment IV for hepatocellular carcinoma in May 2000. In December 2008, the
      elevation of alpha-phetoprotein and the appearance of a heterogeneously enhanced
      mass, with dimensions of 9 x 7 cm, and adjacent to the remnant liver and
      pericardium suggested intrahepatic recurrence with markedly enhanced growth.
      After transcatheter arterial embolization, surgical resection under laparotomy
      combined with median sternotomy was selected. Samples of pericardial fluid showed
      no malignancy after cytological examination. At the superior border of the tumor,
      the confluence of pericardium and diaphragm was displaced, but the tumor itself
      showed a generally expanding but not invasive growth. The resected tumor showed
      moderately differentiated hepatocellular carcinoma whose pathology revealed a
      peritoneal implantation to the diaphragm. The patient is in good health without
      any postoperative complications or any further sign of recurrence.

PMID- 20049171
TI  - Eosinophils and oral squamous cell carcinoma: a short review.
AB  - The eosinophil cell has been related as a prognostic indicator for cancers.
      However, its exact function in tumour behaviour is still not clearly defined. In
      the oral cavity the presence of eosinophils can be a favourable prognostic
      indicator as well as it may be associated with a poor prognosis. In this short
      review, we briefly summarize the role of the eosinophils in the general context
      of immunoregulation and its relation to oral squamous cell carcinoma.

PMID- 20049170
TI  - Role of chemokine network in the development and progression of ovarian cancer: a
      potential novel pharmacological target.
AB  - Ovarian cancer is the most common type of gynecologic malignancy. Despite
      advances in surgery and chemotherapy, the survival rate is still low since most
      ovarian cancers relapse and become drug-resistant. Chemokines are small
      chemoattractant peptides mainly involved in the immune responses. More recently,
      chemokines were also demonstrated to regulate extra-immunological functions. It
      was shown that the chemokine network plays crucial functions in the tumorigenesis
      in several tissues. In particular the imbalanced or aberrant expression of CXCL12
      and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of
      immunosuppressive cells, neovascularization, and metastasization. In the last
      years, several molecules able to target CXCR4 or CXCL12 have been developed to
      interfere with tumor growth, including pharmacological inhibitors, antagonists,
      and specific antibodies. This chemokine ligand/receptor pair was also proposed to
      represent an innovative therapeutic target for the treatment of ovarian cancer.
      Thus, a thorough understanding of ovarian cancer biology, and how chemokines may
      control these different biological activities might lead to the development of
      more effective therapies. This paper will focus on the current biology of
      CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian
      cancer development.

PMID- 20049172
TI  - Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female
      Reproductive Cancers.
AB  - We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers.
      Members of the miR-200 family target ZEB1, a transcription factor which represses
      E-cadherin and other genes involved in polarity. We demonstrate that the double
      negative feedback loop between miR-200c and ZEB1 is functional in some, but not
      all cell lines. Restoration of miR-200c to aggressive cancer cells causes a
      decrease in migration and invasion. These effects are independent of E-cadherin
      status. Additionally, we observe that restoration of miR-200c to ovarian cancer
      cells causes a decrease in adhesion to laminin. We have previously reported that
      reintroduction of miR-200c to aggressive cells that lack miR-200c expression
      restores sensitivity to paclitaxel. We now prove that this ability is a result of
      direct targeting of class III beta-tubulin (TUBB3). Introduction of a TUBB3
      expression construct lacking the miR-200c target site into cells transfected with
      miR-200c mimic results in no change in sensitivity to paclitaxel. Lastly, we
      observe a decrease in proliferation in cells transfected with miR-200c mimic, and
      cells where ZEB1 is knocked down stably, demonstrating that the ability of miR
      200c to enhance sensitivity to paclitaxel is not due to an increased
      proliferation rate.

PMID- 20049174
TI  - ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic
      Leukemia.
AB  - In this study, Forty-one out of fifty-seven Tunisian children with B-lineage
      acute lymphoblastic leukemia (B-ALL), and without cytogenetically detectable
      recurrent abnormalities at the time of the diagnosis, were evaluated by
      fluorescence in situ hybridization (FISH) for the t(12;21). This translocation
      leads ETV6-RUNX1 (previously TEL-AML1) fusion gene. 16 patients (28%) had ETV6
      RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss
      of the normal ETV6 allele, and three others showed an extra signal of the RUNX1
      gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the
      RUNX1 gene. One out of the 7 patients was also associated with a t(3;12)
      identified by FISH. This is the first Tunisian study in which we report the
      incidence of t(12;21) among childhood B-lineage ALL and in which we have found
      multiple copies of RUNX1. Finally, our findings confirm that additional or
      secondary genetic changes are commonly encountered in pediatric B-lineage ALL
      with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease
      progression.

PMID- 20049173
TI  - Understanding and Targeting the Eukaryotic Translation Initiation Factor eIF4E in
      Head and Neck Cancer.
AB  - The eukaryotic translation initiation factor eIF4E is elevated in about 30% of
      human malignancies including HNSCC where its levels correlate with poor
      prognosis. Here, we discuss the biochemical and molecular underpinnings of the
      oncogenic potential of eIF4E. Studies in human leukemia specimens, and later in a
      mouse model of prostate cancer, strongly suggest that cells with elevated eIF4E
      develop an oncogene dependency to it, making them more sensitive to targeting
      eIF4E than normal cells. We describe several strategies that have been suggested
      for eIF4E targeting in the clinic: the use of a small molecule antagonist of
      eIF4E (ribavirin), siRNA or antisense oligonucleotide strategies, suicide gene
      therapy, and the use of a tissue-targeting 4EBP fusion peptide. The first
      clinical trial targeting eIF4E indicates that ribavirin effectively targets eIF4E
      in poor prognosis leukemia patients and more importantly leads to striking
      clinical responses including complete and partial remissions. Finally, we discuss
      the relevance of these findings to HNSCC.

PMID- 20049175
TI  - An evaluation of potential occupational exposure to asbestiform amphiboles near a
      former vermiculite mine.
AB  - Amphibole asbestos (AA) has been detected on the surface of tree bark in forests
      neighboring an abandoned vermiculite mine near Libby, Montana. In the present
      study, simulations were performed to assess potential AA exposure associated with
      United States Department of Agriculture Forest Service (FS) occupational
      activities. Bark samples were collected prior, and personal breathing zone (PBZ)
      and Tyvek clothing wipe samples were collected during and immediately after
      trials that simulated FS activities. Transmission electron microscopy (TEM)
      analyses revealed AA bark concentrations up to 15 million structures per square
      centimeter (s/cm(2)). AA was detected in 25% of the PBZ TEM samples. AA was
      detected on wipe samples collected from all activities evaluated. This research
      demonstrates the potential for airborne exposure and transport of AA in the
      Kootenai National Forest. These findings are especially relevant to those that
      work in the area and to the general public who may conduct recreational
      activities.

PMID- 20049176
TI  - Fruit and vegetable consumption close to recommendations. A partly web-based
      nationwide dietary survey in Swedish adults.
AB  - BACKGROUND: Fruit and vegetables (F&V) are strongly associated with health. The
      latest Swedish national dietary survey from a decade ago showed that consumption
      of F&V was below recommended levels. However, current consumption in different
      subgroups is not well known. OBJECTIVE: To investigate the consumption of various
      F&V types in Swedish adults grouped according to sociodemographic factors and
      self-reported physical activity (PA). DESIGN: A cross-sectional survey using a
      quantitative pen-and-paper or web-based questionnaire in a population-based
      random sample of adults 18-84 years (final n=1,304; 51%). A self-administered 24
      h recall and a food frequency questionnaire (FFQ) were used to measure F&V
      consumption. Data on gender, age, education level, country of birth, and PA
      (hours/week) were included as grouping variables. Besides descriptive data, two
      sample t-tests and non-parametric tests were performed. A P-value <0.01 was
      regarded as significant. RESULTS: Mean F&V consumption based on the self
      administered 24-h recall was close to the recommended five portions/day: 5.4 (99%
      CI 5.1-5.6) portions/day among women and 4.7 (4.4-5.0) portions/day among men
      (P<0.001). Also the FFQ showed that women generally consumed more F&V than men
      did. Consumption was lowest among respondents with </= 0.5 h self-reported
      PA/week (P</=0.001), as well as among men born in Sweden (P=0.006). F&V were
      consumed in almost equal amounts, and fresh F&V were most popular. Intake of
      berries and cooked F&V was relatively low. CONCLUSION: The present study shows a
      relatively high F&V consumption close to the recommended five portions per day.
      Gender differences still exist. Also PA and country of birth were significantly
      associated with F&V consumption.

PMID- 20049177
TI  - Environment and health in china: challenges and opportunities.

PMID- 20049178
TI  - Human data on bisphenol a and neurodevelopment.

PMID- 20049179
TI  - Tackling the research challenges of health and climate change.

PMID- 20049180
TI  - Lead exposures from car batteries--a global problem.

PMID- 20049181
TI  - Periodontal disease and environmental cadmium exposure.

PMID- 20049184
TI  - PERSISTENT ORGANIC POLLUTANTS: melting glaciers release frozen toxicants.

PMID- 20049185
TI  - HAZARDOUS WASTE: GAO grades hanford cleanup.

PMID- 20049187
TI  - CHILDREN'S HEALTH: less pollution, less earache?

PMID- 20049188
TI  - RESEARCH ISSUES AND INITIATIVES: NIEHS funds human BPA research.

PMID- 20049189
TI  - Out of plumb: when water treatment causes lead contamination.

PMID- 20049190
TI  - Communication gap: the disconnect between what scientists say and what the public
      hears.

PMID- 20049191
TI  - Hit or miss?: benefits and risks of using nanoparticles for in situ remediation.

PMID- 20049192
TI  - Cadmium and breast cancer: exposure associated with Basal-like phenotype.

PMID- 20049193
TI  - Chronicle of a health crisis: global implications of the 2008 melamine event.

PMID- 20049194
TI  - Pesticides and Parkinson's disease: the legacy of contaminated well water.

PMID- 20049195
TI  - Hypothesis: a unifying mechanism for nutrition and chemicals as lifelong
      modulators of DNA hypomethylation.
AB  - BACKGROUND: Although both nutrition and chemicals are important environmental
      factors modulating epigenetic changes, they are commonly studied separately by
      researchers in different fields. However, these two environmental factors cannot
      be separated from each other in the real world because a number of chemical
      agents contaminate food chains. OBJECTIVE: We propose a unifying mechanism that
      can link epigenetic alterations in relation to DNA hypomethylation due to
      chemical agents and to nutrient deficiency or imbalance, emphasizing the
      importance of an integrative approach in the field of environmental epidemiology.
      DISCUSSION: Methyl groups from S-adenosylmethionine (SAM) are needed for DNA
      methylation. Diets low in sources of methyl groups can lead to global DNA
      hypomethylation by impairing synthesis of SAM. However, even without nutritional
      deficiency, enhanced need to synthesize glutathi-one (GSH) can impair synthesis
      of SAM and perturb DNA methylation, because the methylation cycle and the GSH
      synthesis pathways are biochemically linked. Exposure to environmental chemicals
      is a common situation in which the need for GSH synthesis is enhanced, because
      GSH is consumed to conjugate diverse chemicals. Given that GSH conjugation
      happens at any chemical dose, this hypothesis is relevant even at exposures below
      the high doses that cause toxicologic responses. CONCLUSION: At present, general
      populations are exposed to a large number of chemicals, each at a very low dose.
      Thus, DNA hypomethylation due to chemical exposure may be common in modern
      societies and can synergistically interact with nutrition-induced DNA
      hypomethylation.

PMID- 20049196
TI  - The melamine incident: implications for international food and feed safety.
AB  - BACKGROUND: A major food safety incident in China was made public in September
      2008. Kidney and urinary tract effects, including kidney stones, affected about
      300,000 Chinese infants and young children, with six reported deaths. Melamine
      had been deliberately added at milk-collecting stations to diluted raw milk
      ostensibly to boost its protein content. Subsequently, melamine has been detected
      in many milk and milk-containing products, as well as other food and feed
      products, which were also exported to many countries worldwide. OBJECTIVES: The
      melamine event represents one of the largest deliberate food contamination
      incidents. We provide a description and analysis of this event to determine the
      global implications on food and feed safety. DISCUSSIONS: A series of factors,
      including the intentional character of the milk contamination, the young age of
      the population affected, the large number of potentially contaminated products,
      the global distribution of these products, and the delay in reporting led this
      event to take on unexpected proportions. This incident illustrated the complexity
      of international trade of food products and food ingredients that required
      immediate actions at international level. CONCLUSION: Managing food-safety events
      should be done internationally and early on as soon as multinational consequences
      are expected. Collaboration between food-safety authorities worldwide is needed
      to efficiently exchange information and to enable tracking and recalling of
      affected products to ensure food safety and to protect public health.

PMID- 20049197
TI  - Epidemiology, public health, and the rhetoric of false positives.
AB  - BACKGROUND: As an observational science, epidemiology is regarded by some
      researchers as inherently flawed and open to false results. In a recent paper,
      Boffetta et al. [Boffetta P, McLaughlin JK, LaVecchia C, Tarone RE, Lipworth L,
      Blot WJ. False-positive results in cancer epidemiology: a plea for
      epistemological modesty. J Natl Cancer Inst 100:988-995 (2008)] argued that
      "epidemiology is particularly prone to the generation of false-positive results."
      They also said "the tendency to emphasize and over-interpret what appear to be
      new findings is commonplace, perhaps in part because of a belief that the
      findings provide information that may ultimately improve public health" and that
      "this tendency to hype new findings increases the likelihood of downplaying
      inconsistencies within the data or any lack of concordance with other sources of
      evidence." The authors supported these serious charges against epidemiology and
      epidemiologists with few examples. Although we acknowledge that false positives
      do occur, we view the position of Boffetta and colleagues on false positives as
      unbalanced and potentially harmful to public health. OBJECTIVE: We aim to provide
      a more balanced evaluation of epidemiology and its contribution to public health
      discourse. DISCUSSION: Boffetta and colleagues ignore the fact that false
      negatives may arise from the very processes that they tout as generating false
      positive results. We further disagree with their proposition that false-positive
      results from a single study will lead to faulty decision making in matters of
      public health importance. In practice, such public health evaluations are based
      on all the data available from all relevant disciplines and never to our
      knowledge on a single study. CONCLUSIONS: The lack of balance by Boffetta and
      colleagues in their evaluation of the impact of false-positive findings on
      epidemiology, the charge that "methodological vigilance is often absent" in
      epidemiologists' interpretation of their own results, and the false
      characterization of how epidemiologic findings are used in societal decision
      making all undermine a major source of information regarding disease risks. We
      reaffirm the importance of epidemiologic evidence as a critical component of the
      foundation of public health protection.

PMID- 20049198
TI  - Nanotechnology and in situ remediation: a review of the benefits and potential
      risks.
AB  - OBJECTIVE: Although industrial sectors involving semiconductors; memory and
      storage technologies; display, optical, and photonic technologies; energy;
      biotechnology; and health care produce the most products that contain
      nanomaterials, nanotechnology is also used as an environmental technology to
      protect the environment through pollution prevention, treatment, and cleanup. In
      this review, we focus on environmental cleanup and provide a background and
      overview of current practice; research findings; societal issues; potential
      environment, health, and safety implications; and future directions for
      nanoremediation. We do not present an exhaustive review of chemistry/engineering
      methods of the technology but rather an introduction and summary of the
      applications of nanotechnology in remediation. We also discuss nanoscale
      zerovalent iron in detail. DATA SOURCES: We searched the Web of Science for
      research studies and accessed recent publicly available reports from the U.S.
      Environmental Protection Agency and other agencies and organizations that
      addressed the applications and implications associated with nanoremediation
      techniques. We also conducted personal interviews with practitioners about
      specific site remediations. DATA SYNTHESIS: We aggregated information from 45
      sites, a representative portion of the total projects under way, to show
      nanomaterials used, types of pollutants addressed, and organizations responsible
      for each site. CONCLUSIONS: Nanoremediation has the potential not only to reduce
      the overall costs of cleaning up large-scale contaminated sites but also to
      reduce cleanup time, eliminate the need for treatment and disposal of
      contaminated soil, and reduce some contaminant concentrations to near zero-all in
      situ. Proper evaluation of nanoremediation, particularly full-scale ecosystem
      wide studies, needs to be conducted to prevent any potential adverse
      environmental impacts.

PMID- 20049200
TI  - Use of remotely sensed data to evaluate the relationship between living
      environment and blood pressure.
AB  - BACKGROUND: Urbanization has been correlated with hypertension (HTN) in
      developing countries undergoing rapid economic and environmental transitions.
      OBJECTIVES: We examined the relationships among living environment (urban,
      suburban, and rural), day/night land surface temperatures (LST), and blood
      pressure in selected regions from the REasons for Geographic and Racial
      Differences in Stroke (REGARDS) cohort. Also, the linking of data on blood
      pressure from REGARDS with National Aeronautics and Space Administration (NASA)
      science data is relevant to NASA's strategic goals and missions, particularly as
      a primary focus of the agency's Applied Sciences Program. METHODS: REGARDS is a
      national cohort of 30,228 people from the 48 contiguous United States with self
      reported and measured blood pressure levels. Four metropolitan regions
      (Philadelphia, PA; Atlanta, GA; Minneapolis, MN; and Chicago, IL) with varying
      geographic and health characteristics were selected for study. Satellite remotely
      sensed data were used to characterize the LST and land cover/land use (LCLU)
      environment for each area. We developed a method for characterizing participants
      as living in urban, suburban, or rural living environments, using the LCLU data.
      These data were compiled on a 1-km grid for each region and linked with the
      REGARDS data via an algorithm using geocoding information. RESULTS: REGARDS
      participants in urban areas have higher systolic and diastolic blood pressure
      than do those in suburban or rural areas, and also a higher incidence of HTN. In
      univariate models, living environment is associated with HTN, but after
      adjustment for known HTN risk factors, the relationship was no longer present.
      CONCLUSION: Further study regarding the relationship between HTN and living
      environment should focus on additional environmental characteristics, such as air
      pollution. The living environment classification method using remotely sensed
      data has the potential to facilitate additional research linking environmental
      variables to public health concerns.

PMID- 20049199
TI  - The breast cancer and the environment research centers: transdisciplinary
      research on the role of the environment in breast cancer etiology.
AB  - OBJECTIVES: We introduce and describe the Breast Cancer and the Environment
      Research Centers (BCERC), a research network with a transdisciplinary approach to
      elucidating the role of environmental factors in pubertal development as a window
      on breast cancer etiology. We describe the organization of four national centers
      integrated into the BCERC network. DATA SOURCES: Investigators use a common
      conceptual framework based on multiple levels of biologic, behavioral, and social
      organization across the life span. The approach connects basic biologic studies
      with rodent models and tissue culture systems, a coordinated multicenter
      epidemiologic cohort study of prepubertal girls, and the integration of community
      members of breast cancer advocates as key members of the research team to
      comprise the network. DATA EXTRACTION: Relevant literature is reviewed that
      describes current knowledge across levels of organization. Individual research
      questions and hypotheses in BCERC are driven by gaps in our knowledge that are
      presented at genetic, metabolic, cellular, individual, and environmental
      (physical and social) levels. DATA SYNTHESIS: As data collection on the cohort,
      animal experiments, and analyses proceed, results will be synthesized through a
      transdisciplinary approach. CONCLUSION: Center investigators are addressing a
      large number of specific research questions related to early pubertal onset,
      which is an established risk factor for breast cancer. BCERC research findings
      aimed at the primary prevention of breast cancer will be disseminated to the
      scientific community and to the public by breast cancer advocates, who have been
      integral members of the research process from its inception.

PMID- 20049201
TI  - Synergistic disruption of external male sex organ development by a mixture of
      four antiandrogens.
AB  - BACKGROUND: By disrupting the action of androgens during gestation, certain
      chemicals present in food, consumer products, and the environment can induce
      irreversible demasculinization and malformations of sex organs among male
      offspring. However, the consequences of simultaneous exposure to such chemicals
      are not well described, especially when they exert their actions by differing
      molecular mechanisms. OBJECTIVES: To fill this gap, we investigated the effects
      of mixtures of a widely used plasticizer, di(2-ethylhexyl) phthalate (DEHP); two
      fungicides present in food, vinclozolin and prochloraz; and a pharmaceutical,
      finasteride, on landmarks of male sexual development in the rat, including
      changes in anogenital distance (AGD), retained nipples, sex organ weights, and
      malformations of genitalia. These chemicals were chosen because they disrupt
      androgen action with differing mechanisms of action. RESULTS: Strikingly, the
      effect of combined exposure to the selected chemicals on malformations of
      external sex organs was synergistic, and the observed responses were greater than
      would be predicted from the toxicities of the individual chemicals. In relation
      to other hallmarks of disrupted male sexual development, including changes in
      AGD, retained nipples, and sex organ weights, the combined effects were dose
      additive. When the four chemicals were combined at doses equal to no observed
      adverse effect levels estimated for nipple retention, significant reductions in
      AGD were observed in male offspring. CONCLUSIONS: Because unhindered androgen
      action is essential for human male development in fetal life, these findings are
      highly relevant to human risk assessment. Evaluations that ignore the possibility
      of combination effects may lead to considerable underestimations of risks
      associated with exposures to chemicals that disrupt male sexual differentiation.

PMID- 20049202
TI  - Cadmium malignantly transforms normal human breast epithelial cells into a basal
      like phenotype.
AB  - BACKGROUND: Breast cancer has recently been linked to cadmium exposure. Although
      not uniformly supported, it is hypothesized that cadmium acts as a
      metalloestrogenic carcinogen via the estrogen receptor (ER). Thus, we studied the
      effects of chronic exposure to cadmium on the normal human breast epithelial cell
      line MCF-10A, which is ER-negative but can convert to ER-positive during
      malignant transformation. METHODS: Cells were continuously exposed to low-level
      cadmium (2.5 muM) and checked in vitro and by xenograft study for signs of
      malignant transformation. Transformant cells were molecularly characterized by
      protein and transcript analysis of key genes in breast cancer. RESULTS: Over 40
      weeks of cadmium exposure, cells showed increasing secretion of matrix
      metalloproteinase-9, loss of contact inhibition, increased colony formation, and
      increasing invasion, all typical for cancer cells. Inoculation of cadmium-treated
      cells into mice produced invasive, metastatic anaplastic carcinoma with
      myoepithelial components. These cadmium-transformed breast epithelial (CTBE)
      cells displayed characteristics of basal-like breast carcinoma, including ER
      alpha negativity and HER2 (human epidermal growth factor receptor 2) negativity,
      reduced expression of BRCA1 (breast cancer susceptibility gene 1), and increased
      CK5 (cytokeratin 5) and p63 expression. CK5 and p63, both breast stem cell
      markers, were prominently overexpressed in CTBE cell mounds, indicative of
      persistent proliferation. CTBE cells showed global DNA hypomethylation and c-myc
      and k-ras overexpression, typical in aggressive breast cancers. CTBE cell
      xenograft tumors were also ER-alpha negative. CONCLUSIONS: Cadmium malignantly
      transforms normal human breast epithelial cells-through a mechanism not requiring
      ER-alpha-into a basal-like cancer phenotype. Direct cadmium induction of a
      malignant phenotype in human breast epithelial cells strongly fortifies a
      potential role in breast cancer.

PMID- 20049203
TI  - Diastereomers of the brominated flame retardant 1,2-dibromo-4-(1,2
      dibromoethyl)cyclohexane induce androgen receptor activation in the hepg2
      hepatocellular carcinoma cell line and the lncap prostate cancer cell line.
AB  - BACKGROUND: Reported incidences of prostate cancer and masculinization of animals
      indicate a release of compounds with androgenic properties into the environment.
      Large numbers of environmental pollutants have been screened to identify such
      compounds; however, not until recently was 1,2-dibromo-4-(1,2
      dibromoethyl)cyclohexane (TBECH) identified as the first potent activator of the
      human androgen receptor (hAR). TBECH has been found in beluga whales and bird
      eggs and has also been found to be maternally transferred in zebrafish.
      OBJECTIVES: In the present study we investigated interaction energies between
      TBECH diastereomers (alpha, beta, gamma, and delta) and the hAR, and their
      ability to activate the receptor and induce prostate-specific antigen (PSA)
      expression in vitro. METHODS: We performed computational modeling to determine
      interaction energies between the ligand and the AR ligand-binding site, and
      measured in vitro competitive binding assays for AR by polarization fluorometry
      analysis. We used enzyme-linked immunosorbent assays to determine PSA activity in
      LNCaP and HepG2 cells. RESULTS: We found the gamma and delta diastereomers to be
      more potent activators of hAR than the alpha and beta diastereomers, which was
      confirmed in receptor binding studies. All TBECH diastereomers induced PSA
      expression in LNCaP cells even though the AR present in these cells is mutated
      (T877A). Modeling studies of LNCaP AR revealed that TBECH diastereomers bound to
      the receptor with a closer distance to the key amino acids in the ligand-binding
      domain, indicating stronger binding to the mutated receptor. CONCLUSIONS: The
      present study demonstrates the ability of TBECH to activate the hAR, indicating
      that it is a potential endocrine disruptor.

PMID- 20049204
TI  - Changes in urinary arsenic methylation profiles in a 15-year interval after
      cessation of arsenic ingestion in southwest Taiwan.
AB  - BACKGROUND: Inorganic arsenic (iAs) is carcinogenic to humans. Methylated
      metabolites of arsenic (As) found in the urine could serve as potential tools for
      screening and early detection of cancer in populations exposed to As. Relatively
      little information is available regarding changes in As methylation profiles
      after cessation of As exposure. OBJECTIVE: We examined the changes in urinary
      arsenic (uAs) species profiles over 15 years in a cancer-free population that has
      ceased heavy and prolonged ingestion of As. METHODS: In 1989, a cohort study was
      carried out with 1,081 adults who resided in three villages in southwestern
      Taiwan where arseniasis was hyperendemic. After 15 years of follow-up, a subgroup
      of 205 cancer-free participants had completed all interviews and had uAs
      methylation data available. We used this group in our statistical analysis.
      Arsenic species were measured by high-performance liquid chromatography-hydride
      generation-atomic absorption spectrometry. RESULTS: We compared the initial
      analyses from 1989 with those performed 15 years later and found that the average
      differences for the proportion of urinary iAs, monomethylarsonic acid (MMA(V)),
      and dimethylarsinic acid (DMA(V)) were -4.90%, -6.80%, and 11.69%, respectively.
      The elderly and those residents with longer periods of consuming high-As artesian
      well water exhibited greater changes (decreases) in %MMA(V). CONCLUSION: The As
      methylation profiles indicate increased efficiency in As metabolism in residents
      after cessation of long-term exposure to high-level As. Moreover, the decreased
      %MMA(V) was more pronounced in the elderly cancer-free subcohort subjects.

PMID- 20049205
TI  - Toxicology in the fast lane: application of high-throughput bioassays to detect
      modulation of key enzymes and receptors.
AB  - BACKGROUND: Legislation at state, federal, and international levels is requiring
      rapid evaluation of the toxicity of numerous chemicals. Whole-animal toxicologic
      studies cannot yield the necessary throughput in a cost-effective fashion,
      leading to a critical need for a faster and more cost-effective toxicologic
      evaluation of xenobiotics. OBJECTIVES: We tested whether mechanistically based
      screening assays can rapidly provide information on the potential for compounds
      to affect key enzymes and receptor targets, thus identifying those compounds
      requiring further in-depth analysis. METHODS: A library of 176 synthetic
      chemicals was prepared and examined in a high-throughput screening (HTS) manner
      using nine enzyme-based and five receptor-based bioassays. RESULTS: All the
      assays have high Z' values, indicating good discrimination among compounds in a
      reliable fashion, and thus are suitable for HTS assays. On average, three
      positive hits were obtained per assay. Although we identified compounds that were
      previously shown to inhibit a particular enzyme class or receptor, we
      surprisingly discovered that triclosan, a microbiocide present in personal care
      products, inhibits carboxylesterases and that dichlone, a fungicide, strongly
      inhibits the ryanodine receptors. CONCLUSIONS: Considering the need to rapidly
      screen tens of thousands of anthropogenic compounds, our study shows the
      feasibility of using combined HTS assays as a novel approach toward obtaining
      toxicologic data on numerous biological end points. The HTS assay approach is
      very useful to quickly identify potentially hazardous compounds and to prioritize
      them for further in-depth studies.

PMID- 20049206
TI  - The C8 health project: design, methods, and participants.
AB  - BACKGROUND: The C8 Health Project was created, authorized, and funded as part of
      the settlement agreement reached in the case of Jack W. Leach, et al. v. E.I. du
      Pont de Nemours & Company (no. 01-C-608 W.Va., Wood County Circuit Court, filed
      10 April 2002). The settlement stemmed from the perfluorooctanoic acid (PFOA, or
      C8) contamination of drinking water in six water districts in two states near the
      DuPont Washington Works facility near Parkersburg, West Virginia. OBJECTIVES:
      This study reports on the methods and results from the C8 Health Project, a
      population study created to gather data that would allow class members to know
      their own PFOA levels and permit subsequent epidemiologic investigations.
      METHODS: Final study participation was 69,030, enrolled over a 13-month period in
      2005-2006. Extensive data were collected, including demographic data, medical
      diagnoses (both self-report and medical records review), clinical laboratory
      testing, and determination of serum concentrations of 10 perfluorocarbons (PFCs).
      Here we describe the processes used to collect, validate, and store these health
      data. We also describe survey participants and their serum PFC levels. RESULTS:
      The population geometric mean for serum PFOA was 32.91 ng/mL, 500% higher than
      previously reported for a representative American population. Serum
      concentrations for perfluorohexane sulfonate and perfluorononanoic acid were
      elevated 39% and 73% respectively, whereas perfluorooctanesulfonate was present
      at levels similar to those in the U.S. population. CONCLUSIONS: This largest
      known population study of community PFC exposure permits new evaluations of
      associations between PFOA, in particular, and a range of health parameters. These
      will contribute to understanding of the biology of PFC exposure. The C8 Health
      Project also represents an unprecedented effort to gather basic data on an
      exposed population; its achievements and limitations can inform future legal
      settlements for populations exposed to environmental contaminants.

PMID- 20049207
TI  - Oral exposure to genistin, the glycosylated form of genistein, during neonatal
      life adversely affects the female reproductive system.
AB  - BACKGROUND: Developmental exposure to environmental estrogens is associated with
      adverse consequences later in life. Exposure to genistin (GIN), the glycosylated
      form of the phytoestrogen genistein (GEN) found in soy products, is of concern
      because approximately 20% of U.S. infants are fed soy formula. High circulating
      levels of GEN have been measured in the serum of these infants, indicating that
      GIN is readily absorbed, hydrolyzed, and circulated. OBJECTIVES: We investigated
      whether orally administered GIN is estrogenic in neonatal mice and whether it
      causes adverse effects on the developing female reproductive tract. METHODS:
      Female CD-1 mice were treated on postnatal days 1-5 with oral GIN (6.25, 12.5,
      25, or 37.5 mg/kg/day; GEN-equivalent doses), oral GEN (25, 37.5, or 75
      mg/kg/day), or subcutaneous GEN (12.5, 20, or 25 mg/kg/day). Estrogenic activity
      was measured on day 5 by determining uterine wet weight gain and induction of the
      estrogen-responsive gene lactoferrin. Vaginal opening, estrous cyclicity,
      fertility, and morphologic alterations in the ovary/reproductive tract were
      examined. RESULTS: Oral GIN elicited an estrogenic response in the neonatal
      uterus, whereas the response to oral GEN was much weaker. Oral GIN altered
      ovarian differentiation (i.e., multioocyte follicles), delayed vaginal opening,
      caused abnormal estrous cycles, decreased fertility, and delayed parturition.
      CONCLUSIONS: Our results support the idea that the dose of the physiologically
      active compound reaching the target tissue, rather than the administered dose or
      route, is most important in modeling chemical exposures. This is particularly
      true with young animals in which phase II metabolism capacity is underdeveloped
      relative to adults.

PMID- 20049208
TI  - Household exposures to polybrominated diphenyl ethers (PBDEs) in a Wisconsin
      Cohort.
AB  - BACKGROUND: Human exposure to polybrominated diphenyl ethers (PBDEs) is virtually
      universal in the United States. Although the uses of these chemicals as flame
      retardants in fabrics, foams, and plastics are well defined, human exposure
      pathways are not well understood. OBJECTIVES: This study was designed to assess
      current PBDE body burdens and identify residential sources of exposure among 29
      men and 15 women in 38 households. METHODS: Portable X-ray fluorescence (XRF)
      analyzers were used to measure bromine levels in upholstered furnishings,
      bedding, vehicle interiors, and electronic devices. Vacuum cleaner contents,
      indoor air samples, and blood sera were analyzed for PBDE congeners using
      conventional gas chromatograph methods. RESULTS: Bromine levels varied widely
      within similar household items. The greatest range for upholstered items was
      found among vehicle seat cushions (7-30,600 ppm). For electronic devices,
      television sets ranged from 4 ppm to 128,300 ppm. Based on mixed effects
      modeling, adjusting for couple households, the bromine content in the
      participants' sleeping pillows and primary vehicle seat cushions were the
      strongest predictors of log lipid-adjusted blood serum PBDE concentrations (p
      values = 0.005 and 0.03, respectively). The total pentaBDE congener levels found
      in dust samples and in passive air samples were not significant predictors of
      blood sera levels. CONCLUSIONS: This study demonstrates the usefulness of the
      portable XRF analyzer in identifying household items that may contribute to human
      exposure to PBDEs.

PMID- 20049209
TI  - Lung inflammation, injury, and proliferative response after repetitive
      particulate hexavalent chromium exposure.
AB  - BACKGROUND: Chronic inflammation is implicated in the development of several
      human cancers, including lung cancer. Certain particulate hexavalent chromium
      [Cr(VI)] compounds are well-documented human respiratory carcinogens that release
      genotoxic soluble chromate and are associated with fibrosis, fibrosarcomas,
      adenocarcinomas, and squamous cell carcinomas of the lung. Despite this, little
      is known about the pathologic injury and immune responses after repetitive
      exposure to particulate chromates. OBJECTIVES: In this study we investigated the
      lung injury, inflammation, proliferation, and survival signaling responses after
      repetitive exposure to particulate chromate. METHODS: BALB/c mice were
      repetitively treated with particulate basic zinc chromate or saline using an
      intranasal exposure regimen. We assessed lungs for Cr(VI)-induced changes by
      bronchoalveolar lavage, histologic examination, and immunohistochemistry.
      RESULTS: Single exposure to Cr(VI) resulted in inflammation of lung tissue that
      persists for up to 21 days. Repetitive Cr(VI) exposure induced a neutrophilic
      inflammatory airway response 24 hr after each treatment. Neutrophils were
      subsequently replaced by increasing numbers of macrophages by 5 days after
      treatment. Repetitive Cr(VI) exposure induced chronic peribronchial inflammation
      with alveolar and interstitial pneumonitis dominated by lymphocytes and
      macrophages. Moreover, chronic toxic mucosal injury was observed and accompanied
      by increased airway pro-matrix metalloprotease-9. Injury and inflammation
      correlated with airways becoming immunoreactive for phosphorylation of the
      survival signaling protein Akt and the proliferation marker Ki-67. We observed a
      reactive proliferative response in epithelial cells lining airways of chromate
      exposed animals. CONCLUSIONS: These data illustrate that repetitive exposure to
      particulate chromate induces chronic injury and an inflammatory microenvironment
      that may promote Cr(VI) carcinogenesis.

PMID- 20049210
TI  - Behavioral changes in aging but not young mice after neonatal exposure to the
      polybrominated flame retardant decaBDE.
AB  - BACKGROUND: After several decades of commercial use, the flame-retardant
      chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites are
      pervasive environmental contaminants and are detected in the human body.
      Decabrominated diphenyl ether (decaBDE) is currently the only PBDE in production
      in the United States. OBJECTIVES: Little is known about the health effects of
      decaBDE. In the present study we examined the effects of neonatal decaBDE
      exposure on behavior in mice at two ages. METHODS: Neonatal male and female
      C57BL6/J mice were exposed to a daily oral dose of 0, 6, or 20 mg/kg decaBDE from
      postnatal days 2 through 15. Two age groups were examined: a cohort that began
      training during young adulthood and an aging cohort of littermates that began
      training at 16 months of age. Both cohorts were tested on a series of operant
      procedures that included a fixed-ratio 1 schedule of reinforcement, a fixed
      interval (FI) 2-min schedule, and a light-dark visual discrimination. RESULTS: We
      observed minimal effects on the light-dark discrimination in the young cohort,
      with no effects on the other tasks. The performance of the aging cohort was
      significantly affected by decaBDE. On the FI schedule, decaBDE exposure increased
      the overall response rate. On the light-dark discrimination, older treated mice
      learned the task more slowly, made fewer errors on the first-response choice of a
      trial but more perseverative errors after an initial error, and had lower
      latencies to respond compared with controls. Effects were observed in both dose
      groups and sexes on various measures. CONCLUSIONS: These findings suggest that
      neonatal decaBDE exposure produces effects on behavioral tasks in older but not
      younger animals. The behavioral mechanisms responsible for the pattern of
      observed effects may include increased impulsivity, although further research is
      required.

PMID- 20049211
TI  - Well-water consumption and Parkinson's disease in rural California.
AB  - INTRODUCTION: Investigators have hypothesized that consuming pesticide
      contaminated well water plays a role in Parkinson's disease (PD), and several
      previous epidemiologic studies support this hypothesis. OBJECTIVES: We
      investigated whether consuming water from private wells located in areas with
      documented historical pesticide use was associated with an increased risk of PD.
      METHODS: We employed a geographic information system (GIS)-based model to
      estimate potential well-water contamination from agricultural pesticides among
      368 cases and 341 population controls enrolled in the Parkinson's Environment and
      Genes Study (PEG). We separately examined 6 pesticides (diazinon, chlorpyrifos,
      propargite, paraquat, dimethoate, and methomyl) from among 26 chemicals selected
      for their potential to pollute groundwater or for their interest in PD, and
      because at least 10% of our population was exposed to them. RESULTS: Cases were
      more likely to have consumed private well water and to have consumed it on
      average 4.3 years longer than controls (p = 0.02). High levels of possible well
      water contamination with methomyl [odds ratio (OR) = 1.67; 95% confidence
      interval (CI), 1.00-2.78]), chlorpyrifos (OR = 1.87; 95% CI, 1.05-3.31), and
      propargite (OR = 1.92; 95% CI, 1.15-3.20) resulted in approximately 70-90%
      increases in relative risk of PD. Adjusting for ambient pesticide exposures only
      slightly attenuated these increases. Exposure to a higher number of water-soluble
      pesticides and organophosphate pesticides also increased the relative risk of PD.
      CONCLUSION: Our study, the first to use agricultural pesticide application
      records, adds evidence that consuming well water presumably contaminated with
      pesticides may play a role in the etiology of PD.

PMID- 20049213
TI  - Cancer risk disparities between hispanic and non-hispanic white populations: the
      role of exposure to indoor air pollution.
AB  - BACKGROUND: Hispanics are the fastest growing minority group in the United
      States; however, minimal information is available on their cancer risks from
      exposures to hazardous air pollutants (HAPs) and how these risks compare to risks
      to non-Hispanic whites. METHODS: We estimated the personal exposure and cancer
      risk of Hispanic and white adults who participated in the Relationships of
      Indoor, Outdoor, and Personal Air (RIOPA) study. We evaluated 12 of the sampled
      volatile organic compounds and carbonyls and identified the HAPs of most concern
      and their possible sources. Furthermore, we examined sociodemographic factors and
      building characteristics. RESULTS: Cumulative cancer risks (CCRs) estimated for
      Hispanics (median = 519 x 10(-6), 90th percentile = 3,968 x 10(-6)) and for
      whites (median = 443 x 10(-6), 90th percentile = 751 x 10(-6)) were much greater
      than the U.S. Environmental Protection Agency (EPA) benchmark of 10(-6).
      Cumulative risks were dominated by formaldehyde and p-dichlorobenzene (p-DCB)
      and, to a lesser extent, by acetaldehyde, chloroform, and benzene. Exposure to
      all of these compounds except benzene was primarily due to indoor residential
      sources. Hispanics had statistically higher CCRs than did whites (p </= 0.05)
      because of differences in exposure to p-DCB, chloroform, and benzene.
      Formaldehyde was the largest contributor to CCR for 69% of Hispanics and 88% of
      whites. Cancer risks for pollutants emitted indoors increased in houses with
      lower ventilation rates. CONCLUSIONS: Hispanics appear to be disproportionately
      affected by certain HAPs from indoor and outdoor sources. Policies that aim to
      reduce risk from exposure to HAPs for the entire population and population
      subgroups should consider indoor air pollution.

PMID- 20049212
TI  - Traffic-related air pollution, oxidative stress genes, and asthma (ECHRS).
AB  - BACKGROUND: Traffic-related air pollution is related with asthma, and this
      association may be modified by genetic factors. OBJECTIVES: We investigated the
      role of genetic polymorphisms potentially modifying the association between home
      outdoor levels of modeled nitrogen dioxide and asthma. METHODS: Adults from 13
      cities of the second European Community Respiratory Health Survey (ECRHS II) were
      included (n = 2,920), for whom both DNA and outdoor NO(2) estimates were
      available. Home addresses were geocoded and linked to modeled outdoor NO(2)
      estimates, as a marker of local traffic-related pollution. We examined asthma
      prevalence and evaluated polymorphisms in genes involved in oxidative stress
      pathways [gluthatione S-transferases M1 (GSTM1), T1 (GSTT1), and P1 (GSTP1) and
      NAD(P)H:quinine oxidoreductase (NQO1)], inflammatory response [tumor necrosis
      factor alpha (TNFA)], immunologic response [Toll-like receptor 4 (TLR4)], and
      airway reactivity [adrenergic receptor beta2 (ADRB2)]. RESULTS: The association
      between modeled NO(2) and asthma prevalence was significant for carriers of the
      most common genotypes of NQO1 rs2917666 [odds ratio (OR) = 1.54; 95% confidence
      interval (CI), 1.10-2.24], TNFA rs2844484 (OR = 2.02; 95% CI, 1.30-3.27). For new
      onset asthma, the effect of NO(2) was significant for the most common genotype of
      NQO1 rs2917666 (OR = 1.52; 95% CI, 1.09-2.16). A significant interaction was
      found between NQO1 rs2917666 and NO(2) for asthma prevalence (p = 0.02) and new
      onset asthma (p = 0.04). CONCLUSIONS: Genetic polymorphisms in the NQO1 gene are
      related to asthma susceptibility among persons exposed to local traffic-related
      air pollution. This points to the importance of antioxidant pathways in the
      protection against the effects of air pollution on asthma.

PMID- 20049214
TI  - Mercury induces an unopposed inflammatory response in human peripheral blood
      mononuclear cells in vitro.
AB  - BACKGROUND: The human immune response to mercury is not well characterized
      despite the body of evidence that suggests that Hg can modulate immune responses,
      including the induction of autoimmune disease in some mouse models. Dysregulation
      of cytokine signaling appears to play an important role in the etiology of Hg
      induced autoimmunity in animal models. OBJECTIVES: In this study, we
      systematically investigated the human immune response to Hg in vitro in terms of
      cytokine release. METHODS: Human peripheral blood mononuclear cells (PBMCs) were
      isolated from 20 volunteers who donated blood six separate times. PBMCs were
      cultured with lipopolysaccharide and concentrations of mercuric chloride
      (HgCl(2)) up to 200 nM. Seven cytokines representing important pathways in
      physiologic and pathologic immune responses were measured in supernatants. We
      used multilevel models to account for the intrinsic clustering in the cytokine
      data due to experimental design. RESULTS: We found a consistent increase in the
      release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor
      necrosis factor-alpha, and concurrent decrease in release of the antiinflammatory
      cytokines interleukin 1-receptor antagonist (IL-1Ra) and IL-10 in human PBMCs
      treated with subcytotoxic concentrations of HgCl(2). IL-4, IL-17, and interferon
      gamma increased in a concentration-response manner. These results were replicated
      in a second, independently recruited population of 20 different volunteers.
      CONCLUSIONS: Low concentrations of HgCl(2) affect immune function in human cells
      by dysregulation of cytokine signaling pathways, with the potential to influence
      diverse health outcomes such as susceptibility to infectious disease or risk of
      autoimmunity.

PMID- 20049215
TI  - Residential exposure to traffic and spontaneous abortion.
AB  - BACKGROUND: Studies have shown associations between air pollution or traffic
      exposure and adverse birth outcomes, such as low birth weight. However, very few
      studies have examined the effect of traffic emissions on spontaneous abortion
      (SAB). OBJECTIVE: The goal of this study was to determine whether residential
      exposure to vehicular traffic was associated with SAB. METHODS: Pregnant women
      from a prepaid health plan in California were recruited into a prospective cohort
      study in 1990-1991. Three measures of traffic exposure were constructed for the
      4,979 participants using annual average daily traffic (AADT) counts near each
      residence and distance from residence to major roads. SAB was examined in
      relation to the traffic exposure measures using logistic regression adjusting for
      a number of demographic and lifestyle variables. RESULTS: Of the traffic
      measures, maximum annual average traffic within 50 m showed the strongest
      association with SAB, although it was not statistically significant. The adjusted
      odds ratio (AOR) for the top 90th percentile (AADT greater than 15,199) versus
      the bottom 75th percentile (AADT = 0-1,089) was 1.18 [95% confidence interval
      (CI), 0.87-1.60]. However, subgroup analyses showed statistically significant
      associations for traffic with SAB among African Americans (AOR = 3.11; 95% CI,
      1.26-7.66) and nonsmokers (AOR = 1.47; 95% CI, 1.07-2.04). CONCLUSION: In this
      cohort, living within 50 m of a road with AADT of 15,200 or more was
      significantly associated with SAB among African Americans and nonsmokers. Further
      research is needed to confirm these results and possibly elucidate the mechanisms
      responsible for the findings.

PMID- 20049216
TI  - Prenatal bisphenol A exposure and early childhood behavior.
AB  - BACKGROUND: Prenatal exposure to bisphenol A (BPA) increases offspring aggression
      and diminishes differences in sexually dimorphic behaviors in rodents. OBJECTIVE:
      We examined the association between prenatal BPA exposure and behavior in 2-year
      old children. METHODS: We used data from 249 mothers and their children in
      Cincinnati, Ohio (USA). Maternal urine was collected around 16 and 26 weeks of
      gestation and at birth. BPA concentrations were quantified using high-performance
      liquid chromatography-isotope-dilution tandem mass spectrometry. Child behavior
      was assessed at 2 years of age using the second edition of the Behavioral
      Assessment System for Children (BASC-2). The association between prenatal BPA
      concentrations and BASC-2 scores was analyzed using linear regression. RESULTS:
      Median BPA concentrations were 1.8 (16 weeks), 1.7 (26 weeks), and 1.3 (birth)
      ng/mL. Mean (+/- SD) BASC-2 externalizing and internalizing scores were 47.6 +/-
      7.8 and 44.8 +/- 7.0, respectively. After adjustment for confounders, log(10)
      transformed mean prenatal BPA concentrations were associated with externalizing
      scores, but only among females [beta = 6.0; 95% confidence interval (CI), 0.1
      12.0]. Compared with 26-week and birth concentrations, BPA concentrations
      collected around 16 weeks were more strongly associated with externalizing scores
      among all children (beta = 2.9; 95% CI, 0.2-5.7), and this association was
      stronger in females than in males. Among all children, measurements collected at
      <or= 16 weeks showed a stronger association (beta = 5.1; 95% CI, 1.5-8.6) with
      externalizing scores than did measurements taken at 17-21 weeks (beta = 0.6; 95%
      CI, -2.9 to 4.1). CONCLUSIONS: These results suggest that prenatal BPA exposure
      may be associated with externalizing behaviors in 2-year-old children, especially
      among female children.

PMID- 20049217
TI  - Prenatal exposure to organohalogens, including brominated flame retardants,
      influences motor, cognitive, and behavioral performance at school age.
AB  - BACKGROUND: Organohalogen compounds (OHCs) are known to have neurotoxic effects
      on the developing brain. OBJECTIVE: We investigated the influence of prenatal
      exposure to OHCs, including brominated flame retardants, on motor, cognitive, and
      behavioral outcome in healthy children of school age. METHODS: This study was
      part of the prospective Groningen infant COMPARE (Comparison of Exposure-Effect
      Pathways to Improve the Assessment of Human Health Risks of Complex Environmental
      Mixtures of Organohalogens) study. It included 62 children in whose mothers the
      following compounds had been determined in the 35th week of pregnancy: 2,2'-bis
      (4 chlorophenyl)-1,1'-dichloroethene, pentachlorophenol (PCP), polychlorinated
      biphenyl congener 153 (PCB-153), 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4OH
      CB-107), 4OH-CB-146, 4OH-CB-187, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), BDE
      99, BDE-100, BDE-153, BDE-154, and hexabromocyclododecane. Thyroid hormones were
      determined in umbilical cord blood. When the children were 5-6 years of age, we
      assessed their neuropsychological functioning: motor performance (coordination,
      fine motor skills), cognition (intelligence, visual perception, visuomotor
      integration, inhibitory control, verbal memory, and attention), and behavior.
      RESULTS: Brominated flame retardants correlated with worse fine manipulative
      abilities, worse attention, better coordination, better visual perception, and
      better behavior. Chlorinated OHCs correlated with less choreiform dyskinesia.
      Hydroxylated polychlorinated biphenyls correlated with worse fine manipulative
      abilities, better attention, and better visual perception. The wood protective
      agent (PCP) correlated with worse coordination, less sensory integrity, worse
      attention, and worse visuomotor integration. CONCLUSIONS: Our results demonstrate
      for the first time that transplacental transfer of polybrominated flame
      retardants is associated with the development of children at school age. Because
      of the widespread use of these compounds, especially in the United States, where
      concentrations in the environment are four times higher than in Europe, these
      results cause serious concern.

PMID- 20049218
TI  - A history of alcohol dependence increases the incidence and severity of
      postoperative cognitive dysfunction in cardiac surgical patients.
AB  - Postoperative cognitive dysfunction (POCD) commonly occurs after cardiac surgery.
      We tested the hypothesis that a history of alcohol dependence is associated with
      an increased incidence and severity of POCD in male patients undergoing cardiac
      surgery using cardiopulmonary bypass. Recent verbal and nonverbal memory and
      executive functions were assessed before and one week after surgery in patients
      with or without a history of alcohol dependence. Cognitive function was
      significantly reduced after cardiac surgery in patients with versus without a
      history of alcohol dependence. The results suggest that a history of alcohol
      dependence increases the incidence and severity of POCD after cardiac surgery.

PMID- 20049219
TI  - Chronic traffic-induced PM exposure and self-reported respiratory and
      cardiovascular health in the RHINE Tartu Cohort.
AB  - The relationship between exposure to traffic induced particles, respiratory
      health and cardiac diseases was studied in the RHINE Tartu cohort. A postal
      questionnaire with commonly used questions regarding respiratory symptoms,
      cardiac disease, lifestyle issues such as smoking habits, indoor environment,
      occupation, early life exposure and sleep disorders was sent to 2,460 adults. The
      annual concentrations of local traffic induced particles were modelled with an
      atmospheric dispersion model with traffic flow data, and obtained PM(exhaust)
      concentrations in 40 x 40 m grids were linked with home addresses with GIS. The
      relationship between the level of exhaust particles outside home and self
      reported health problems were analyzed using a multiple logistic regression
      model. We found a significant relation between fine exhaust particles and cardiac
      disease, OR = 1.64 (95% CI 1.12-2.43) for increase in PM(exhaust) corresponding
      to the fifth to the 95th percentile range. The associations also were positive
      but non-significant for hypertension OR = 1.42 (95% CI 0.94-2.13), shortness of
      breath OR = 1.27 (95% CI 0.84-1.94) and other respiratory symptoms.

PMID- 20049220
TI  - Is there a link between wheezing in early childhood and adverse birth outcomes? A
      systematic review.
AB  - We aimed to provide a summary of the existing published knowledge on the
      association between adverse birth outcomes and the development of wheezing during
      the first two years of life. We carried out a systematic review of
      epidemiological studies within the MEDLINE database. Epidemiological studies on
      human subjects, published in English, were included in the review. A
      comprehensive literature search yielded 72 studies for further consideration.
      Following the application of the eligibility criteria we identified nine studies.
      A positive association and an excess risk of wheezing during the first two years
      of life were revealed for adverse birth outcomes.

PMID- 20049222
TI  - Alcoholic pancreatitis: pathogenesis, incidence and treatment with special
      reference to the associated pain.
AB  - Alcoholic pancreatitis continues to stir up controversy. One of the most debated
      points is whether from onset it is a chronic disease or whether it progresses to
      a chronic form after repeated episodes of acute pancreatitis. Histological
      studies on patients with alcoholic pancreatitis have shown that the disease is
      chronic from onset and that alcoholic acute pancreatitis occurs in a pancreas
      already damaged by chronic lesions. Genetic factors may also play a role in the
      pathogenesis of alcoholic disease. The incidence of chronic alcoholic
      pancreatitis seems to have decreased in the last twenty years. Finally, recent
      therapeutic studies which have shown medical or surgical approaches capable of
      reducing the pain episodes in chronic pancreatitis patients will be described.

PMID- 20049223
TI  - Alcohol-induced blackout.
AB  - For a long time, alcohol was thought to exert a general depressant effect on the
      central nervous system (CNS). However, currently the consensus is that specific
      regions of the brain are selectively vulnerable to the acute effects of alcohol.
      An alcohol-induced blackout is the classic example; the subject is temporarily
      unable to form new long-term memories while relatively maintaining other skills
      such as talking or even driving. A recent study showed that alcohol can cause
      retrograde memory impairment, that is, blackouts due to retrieval impairments as
      well as those due to deficits in encoding. Alcoholic blackouts may be complete
      (en bloc) or partial (fragmentary) depending on severity of memory impairment. In
      fragmentary blackouts, cueing often aids recall. Memory impairment during acute
      intoxication involves dysfunction of episodic memory, a type of memory encoded
      with spatial and social context. Recent studies have shown that there are
      multiple memory systems supported by discrete brain regions, and the acute
      effects of alcohol on learning and memory may result from alteration of the
      hippocampus and related structures on a cellular level. A rapid increase in blood
      alcohol concentration (BAC) is most consistently associated with the likelihood
      of a blackout. However, not all subjects experience blackouts, implying that
      genetic factors play a role in determining CNS vulnerability to the effects of
      alcohol. This factor may predispose an individual to alcoholism, as altered
      memory function during intoxication may affect an individual's alcohol
      expectancy; one may perceive positive aspects of intoxication while
      unintentionally ignoring the negative aspects. Extensive research on memory and
      learning as well as findings related to the acute effects of alcohol on the brain
      may elucidate the mechanisms and impact associated with the alcohol-induced
      blackout.

PMID- 20049224
TI  - State adoption of 100% smoke-free acute non federal hospital campus policies.
AB  - To assess the number and percentage of acute care hospitals in the U.S. that have
      adopted smoke-free hospital campus (SFHC) policies, researchers conducted an
      assessment from January 2008 to May 2008 of available data on SFHC policy
      adoption in each state. Slightly more than one third (34.4%) of acute care, non
      Federal hospitals had adopted such policies, with wide variation of policy
      adoption between states.

PMID- 20049226
TI  - Incidence and risk factors of workplace violence on nursing staffs caring for
      chronic psychiatric patients in taiwan.
AB  - This one-year follow-up study determined the incidence and risk factors of
      workplace violence against nursing staff in a psychiatric hospital. The cohort
      members had a website to report events whenever they came across violence. A
      total of 971 events were reported. The incidence rates of physical violence,
      verbal abuse, bullying/mobbing, sexual harassment, and racial harassment were
      1.7, 3.7, 0.2, 0.3, and 0 per staff-year, respectively. Young age, female sex,
      lower education, shorter duration of employment, and high level of anxiety of
      staff seemed to be the determinants of violence. Pre-placement education should
      focus on these staff to reduce workplace violence.

PMID- 20049225
TI  - Agreement between the SCORE and D'Agostino Scales for the classification of high
      cardiovascular risk in sedentary spanish patients.
AB  - BACKGROUND: To evaluate agreement between cardiovascular risk in sedentary
      patients as estimated by the new Framingham-D'Agostino scale and by the SCORE
      chart, and to describe the patient characteristics associated with the observed
      disagreement between the scales. DESIGN: A cross-sectional study was undertaken
      involving a systematic sample of 2,295 sedentary individuals between 40-65 years
      of age seen for any reason in 56 primary care offices. An estimation was made of
      the Pearson correlation coefficient and kappa statistic for the classification of
      high risk subjects (> or =20% according to the Framingham-D'Agostino scale, and >
      or =5% according to SCORE). Polytomous logistic regression models were fitted to
      identify the variables associated with the discordance between the two scales.
      RESULTS: The mean risk in males (35%) was 19.5% +/- 13% with D'Agostino scale,
      and 3.2% +/- 3.3% with SCORE. Among females, they were 8.1% +/- 6.8% and 1.2% +/-
      2.2%, respectively. The correlation between the two scales was 0.874 in males
      (95% CI: 0.857-0.889) and 0.818 in females (95% CI: 0.800-0.834), while the kappa
      index was 0.50 in males (95% CI: 0.44%-0.56%) and 0.61 in females (95% CI: 0.52%
      0.71%). The most frequent disagreement, characterized by high risk according to
      D'Agostino scale but not according to SCORE, was much more prevalent among males
      and proved more probable with increasing age and increased LDL-cholesterol,
      triglyceride and systolic blood pressure values, as well as among those who used
      antihypertensive drugs and smokers. CONCLUSIONS: The quantitative correlation
      between the two scales is very high. Patient categorization as corresponding to
      high risk generates disagreements, mainly among males, where agreement between
      the two classifications is only moderate.

PMID- 20049227
TI  - Impact of co-occurring psychiatric disorders on retention in a methadone
      maintenance program: an 18-month follow-up study.
AB  - We assess the influence of co-occurring psychiatric disorders on retention in 189
      opioid dependent patients in a methadone maintenance treatment (MMT) and
      determine the incidence of psychiatric co-morbidity during an 18-month follow-up
      period. About 68.5 % were retained in the MMT. Neither co-occurring mental
      disorders (chi-square = 0.303, df = 1, p = 0.622) nor methadone doses [85 (88.9)
      vs. 79.2 (85) mg/day, p = 0.672] were related to retention. In the follow-up
      period 19 new diagnoses were made, mainly major depression and antisocial and
      borderline personality disorders. Co-occurring psychiatric disorders should be
      assessed during MMT follow-up.

PMID- 20049228
TI  - Application of the WHO keys of safer food to improve food handling practices of
      food vendors in a poor resource community in Ghana.
AB  - Data was collected from food vendors in a poor resource community in Ghana, which
      showed that the vendors constituted an important source of oro-faecal
      transmission. Following this, the WHO five keys of safer food were utilized in an
      evidence based training programme for the vendors to improve their food handling
      practices. Impact assessment of the food safety training showed that 67.6% of the
      vendors had acquired some knowledge from the workshop and were putting it into
      practice. Lack of food safety equipment was a major hinderance to behavioral
      change among the vendors as far food handling practices are concerned.

PMID- 20049229
TI  - Public health and nursing: a natural partnership.
AB  - The health of individuals occurs within the context of their environment and the
      other individuals they interact with in the communities they live in, work in and
      visit. Promoting the health of the public requires multiple strategies aimed at
      improving the environment, the health knowledge of groups and individuals,
      maintaining adequate food and water, and reducing the spread of disease. Many
      disciplines are needed to meet these goals, but the largest segment of the
      professional health work force required to meet these needs is nursing.
      Historically, nursing leaders in public health such as Florence Nightingale and
      Lillian Wald made significant inroads related to serious health issues because
      they were nurses. Today across the globe, nurses provide the key components of
      public health interventions including well baby care, health education, screening
      and immunization clinics, disaster management and emergency preparedness. With
      the growing nursing shortage in acute care settings, the brain drain of nurses
      from certain areas of the world, the shrinking public dollars for preventive
      health care, the nursing workforce needed to continue to provide these essential
      health care services is threatened. It is essential to put the spot light on
      nursing's role in public health with the hopes of attracting more public funds
      and more nurses to provide these essential services.

PMID- 20049230
TI  - Variation of natural streamflow since 1470 in the middle Yellow River, China.
AB  - Nowadays, as the available water resources throughout the World are becoming
      depleted, in order to manage and plan water resource better, more and more
      attention is being paid into the fluctuating characteristics of water discharges.
      However, the preexisting research was mainly focused on the last half century. In
      this paper, the natural streamflow observed since 1470 at the Sanmenxia station
      in the middle Yellow River basin was collected, and the methods of variation
      coefficient, moving average, Mann-Kendall test and wavelet transform were applied
      to analyze the dynamic characteristics of the streamflow. The results showed
      that, (1) between 1470 and 2007, the natural streamflow changed 200-919 x 10(8)
      m(3), and water discharge varied moderately; (2) in the middle Yellow River
      basin, it appears that the most severe and most persistent droughts during circa
      1868-1990, the periods of 1470s-1490s, 1920s-1930s and 1990s-2000s also presented
      the condition of sustained low flows; (3) the natural streamflow series shows
      increasing and decreasing trends during the periods of 1470-1880 and 1881-2007,
      respectively, but both trends are not significant at >95% confidence; in
      addition, it is still found the streamflow series shows abrupt changes circa
      1845, 1935 and 1960, respectively; (4) within a 250-year scale, there are circa
      11, 26, 67 and 120-year periods for natural streamflow at the Sanmenxia station,
      and the periodicity of the 120-year one is the strongest. The dynamic
      characteristics of natural streamflow is the comprehensive result by many
      influencing factors, such as precipitation, temperature, El Nino-Southern
      Oscillation, sunspots, human activity, etc.

PMID- 20049231
TI  - Leachability of arsenic and heavy metals from mine tailings of abandoned metal
      mines.
AB  - Mine tailings from an abandoned metal mine in Korea contained high concentrations
      of arsenic (As) and heavy metals [e.g., As: 67,336, Fe: 137,180, Cu: 764, Pb:
      3,572, and Zn: 12,420 (mg/kg)]. US EPA method 6010 was an effective method for
      analyzing total arsenic and heavy metals concentrations. Arsenic in the mine
      tailings showed a high residual fraction of 89% by a sequential extraction. In
      Toxicity Characteristic Leaching Procedure (TCLP) and Korean Standard Leaching
      Test (KSLT), leaching concentrations of arsenic and heavy metals were very low
      [e.g., As (mg/L): 0.4 for TCLP and 0.2 for KSLT; cf. As criteria (mg/L): 5.0 for
      TCLP and 1.5 for KSLT].

PMID- 20049232
TI  - Indoor air pollution: an old problem with new challenges.

PMID- 20049233
TI  - Two distinct training methods for a doctrine of life with healthy heart in a low
      socioeconomic society model.
AB  - This study was conducted in three stages in a semi-rural region of Eskisehir,
      Turkey. In the first stage, individuals selected by random sampling were
      evaluated for cardiovascular disease risk factors. In the second stage, Group I
      and Group II training materials were randomly distributed. In the third stage,
      the subjects were screened one year later to assess and determine if there had
      been any changes in their attitudes towards the dangers of cardiovascular
      diseases. The number of active smokers significantly decreased after the training
      in the both groups. The percentage of people with regulated blood pressure
      exhibited an increase in Group II more than Group I.

PMID- 20049234
TI  - Examining factors in the Research Institute on Addictions Self-Inventory (RIASI):
      Associations with alcohol use and problems at assessment and follow-up.
AB  - Impaired driving is a leading cause of alcohol-related deaths and injuries.
      Rehabilitation or remedial programs, involving assessment and screening of
      convicted impaired drivers to determine problem severity and appropriate
      programs, are an important component of society's response to this problem.
      Ontario's remedial program, Back on Track (BOT), involves an assessment process
      that includes administration of the Research Institute on Addictions Self
      Inventory (RIASI) to determine assignment to an education or treatment program.
      The purpose of this study is to identify factors within the RIASI and examine how
      factor scores are associated with alcohol use and problem indicators at
      assessment and six-month follow-up. The sample included 22,298 individuals who
      completed BOT from 2000 to 2005. Principal component factor analysis with varimax
      rotation was conducted on RIASI data and an eight factor solution was retained:
      (1) Negative Affect, (2) Sensation Seeking, (3) Alcohol-Quantity, (4) Social
      Conformity, (5) High Risk Lifestyle, (6) Alcohol Problems, (7) Interpersonal
      Competence, and (8) Family History. Regression analyses were conducted to examine
      associations between factors and alcohol and problem measures obtained at
      assessment and at follow-up. Most factors, except for Interpersonal Competence,
      were associated with more alcohol use and problems at assessment. A similar
      pattern was observed at 6-month follow-up, but interestingly some factors
      (Negative Affect, Sensation Seeking, Alcohol-Quantity and Family History)
      predicted fewer days of alcohol use. The Interpersonal Competence factor was
      associated with significantly lower levels of alcohol use and problems at both
      assessment and follow-up. This work suggests that the RIASI provides information
      on several domains that have important relationships with alcohol problem
      severity and outcomes.

PMID- 20049235
TI  - The role of endocarditis, myocarditis and pericarditis in qualitative and
      quantitative data analysis.
AB  - The current study is the first scientometric analysis of research activity and
      output in the field of inflammatory disorders of the heart (endo-, myo- and
      pericarditis). Scientometric methods are used to compare scientific performance
      on national and on international scale to identify single areas of research
      interest. Interest and research productivity in inflammatory diseases of the
      heart have increased since 1990. The majority of publications about inflammatory
      heart disorders were published in Western Europe and North America. The United
      States of America had a leading position in terms of research productivity and
      quality; half of the most productive authors in this study came from American
      institutions. The analysis of international cooperation revealed research
      activity in countries that are less established in the field of inflammatory
      heart disorder research, such as Brazil, Saudi Arabia and Tunisia. These results
      indicate that future research of heart inflammation may no longer be influenced
      predominantly by a small number of countries. Furthermore, this study revealed
      weaknesses in currently established scientometric parameters (i.e., h-index,
      impact factor) that limit their suitability as measures of research quality. In
      this respect, self-citations should be generally excluded from calculations of h
      index and impact factor.

PMID- 20049236
TI  - Chronic stress and the development of early atherosclerosis: moderating effect of
      endothelial dysfunction and impaired arterial elasticity.
AB  - This study aims to explore the interactive effect of vital exhaustion (VE) and
      endothelial dysfunction on preclinical atherosclerosis, assessed by carotid
      intima-media thickness (IMT). Furthermore, interaction between VE and carotid
      elasticity is examined. Participants were 1,596 young healthy adults from the
      Cardiovascular Risk in Young Finns study. Endothelial dysfunction was measured by
      brachial flow-mediated dilatation (FMD), and carotid elasticity by carotid artery
      compliance (CAC). Significant interactions between FMD and VE, and between CAC
      and VE, for IMT were found in participants with the very lowest FMD and CAC.
      Thus, VE may be harmful if the endothelium is not working properly.

PMID- 20049237
TI  - Health economic assessment: a methodological primer.
AB  - This review article aims to provide an introduction to the methodology of health
      economic assessment of a health technology. Attention is paid to defining the
      fundamental concepts and terms that are relevant to health economic assessments.
      The article describes the methodology underlying a cost study (identification,
      measurement and valuation of resource use, calculation of costs), an economic
      evaluation (type of economic evaluation, the cost-effectiveness plane, trial- and
      model-based economic evaluation, discounting, sensitivity analysis, incremental
      analysis), and a budget impact analysis. Key references are provided for those
      readers who wish a more advanced understanding of health economic assessments.

PMID- 20049238
TI  - Musculoskeletal disorders among cosmetologists.
AB  - A cross-sectional study was performed to investigate the relationships between
      physical, psychosocial, and individual characteristics and different endpoints of
      low back, neck, shoulder, hand/wrist and knee musculoskeletal complaints among
      cosmetologists in Athens, Greece. The study population consisted of 95 female and
      seven male beauty therapists (response rate 90%) with a mean age and duration of
      employment of 38 and 16 years, respectively. Neck pain was the most prevalent
      musculoskeletal complaint, reported by 58% of the subjects, while hand/wrist and
      low back complaints resulted more frequently in self-reported consequences
      (chronicity, care seeking and absenteeism). Significant relationships were found
      between self-reported physical risk factors like prolonged sitting, use of
      vibrating tools, reaching far and awkward body postures and the occurrence of
      musculoskeletal disorders at various body sites. Among psychosocial variables co
      worker support and skill discretion seem to be the most important reflecting
      organizational problems and cognitive-behavioral aspects. The study results also
      suggest that effective intervention strategies most likely have to take into
      account both ergonomic improvements and organizational aspects.

PMID- 20049239
TI  - "This is public health: recycling counts!" Description of a pilot health
      communications campaign.
AB  - This paper describes the development, implementation, and evaluation of a pilot
      recycling campaign. The goal of the campaign was to increase people's awareness
      and knowledge about recycling and the link between a healthy environment and the
      public's health. A total of 258 individuals attended campaign week events and
      completed an initial survey. Results identified inconvenience of recycling
      facility locations as a key barrier to recycling. Post-campaign survey results
      revealed increased recycling of paper, plastic, glass, and cans (p < 0.05). The
      majority of participants "agreed" or "strongly agreed" that as a result of
      campaign messages they had greater awareness about recycling (88.4%) and their
      recycling efforts increased (61.6%).

PMID- 20049240
TI  - Dental caries risk studies revisited: causal approaches needed for future
      inquiries.
AB  - Prediction of high-risk individuals and the multi-risk approach are common
      inquiries in caries risk epidemiology. These studies prepared the ground for
      future studies; specific hypotheses about causal patterns can now be formulated
      and tested applying advanced statistical methods designed for causal studies,
      such as structural equation modeling, path analysis and multilevel modeling.
      Causal studies should employ measurements, analyses and interpretation of
      findings, which are in accordance to causal aims. Examples of causal empirical
      studies from medical and oral research are presented.

PMID- 20049241
TI  - Gender differences in interpersonal problems of alcohol-dependent patients and
      healthy controls.
AB  - Alcohol dependence is a heavy burden on patients, their families, and society.
      Epidemiological studies indicate that alcohol dependence will affect many
      individuals at some time in their lives, with men affected more frequently than
      women. Since alcohol-dependent patients often exhibit a lack of social skills and
      suffer from interpersonal problems, the aim of this study is to elucidate whether
      men and women experience the same interpersonal problems. Eighty-five alcohol
      dependent patients (48 men; 37 women) after detoxification and 62 healthy
      controls (35 men; 27 women) were recruited. Interpersonal problems were measured
      with the Inventory of Interpersonal Problems (IIP-64). Additionally, alcohol
      dependent patients were interviewed with the Alcohol Use Disorders Identification
      Test (AUDIT) and were subtyped according to Lesch's Alcohol Typology (LAT). There
      were no significant gender differences in the AUDIT and LAT between alcohol
      dependent men and women. Interpersonal problems of alcohol-dependent men differed
      significantly in one out of eight dimensions from controls; alcohol-dependent men
      perceive themselves as colder than male controls. Alcohol-dependent women
      differed in four out of eight interpersonal dimensions from female controls.
      Alcohol-dependent women rated themselves as significantly more vindictive, more
      introverted, more overly accommodating and more intrusive than female controls.
      Results suggest that alcohol-dependent men and women suffer from different
      interpersonal problems and furthermore alcohol-dependent women perceive more
      interpersonal problems, whereas the severity of alcohol dependence did not differ
      between the groups. Our findings indicate that alcohol-dependent women may profit
      more from a gender-specific treatment approach aimed at improving treatment
      outcome than alcohol-dependent men.

PMID- 20049242
TI  - Occupational noise exposure and age correction: the problem of selection bias.
AB  - Selection bias often invalidates conclusions about populations based on clinical
      convenience samples. A recent paper in this journal makes two surprising
      assertions about noise-induced permanent threshold shift (NIPTS): first, that
      there is more NIPTS at 2 kHz than at higher frequencies; second, that NIPTS
      declines with advancing age. Neither assertion can be supported with the data
      presented, which were obtained from a clinical sample; both are consistent with
      the hypothesis that people who choose to attend an audiology clinic have worse
      hearing, especially at 2 kHz, than people of the same age and gender who choose
      not to attend.

PMID- 20049243
TI  - Natural environment suitability of China and its relationship with population
      distributions.
AB  - The natural environment factor is one of the main indexes for evaluating human
      habitats, sustained economic growth and ecological health status. Based on
      Geographic Information System (GIS) technology and an analytic hierarchy process
      method, this article presents the construction of the Natural Environment
      Suitability Index (NESI) model of China by using natural environment data
      including climate, hydrology, surface configuration and ecological conditions.
      The NESI value is calculated in grids of 1 km by 1 km through ArcGIS. The spatial
      regularity of NESI is analyzed according to its spatial distribution and
      proportional structure. The relationship of NESI with population distribution and
      economic growth is also discussed by analyzing NESI results with population
      distribution data and GDP data in 1 km by 1 km grids. The study shows that: (1)
      the value of NESI is higher in the East and lower in the West in China; The best
      natural environment area is the Yangtze River Delta region and the worst are the
      northwest of Tibet and southwest of Xinjiang. (2) There is a close correlation
      among natural environment, population distribution and economic growth; the best
      natural environment area, the Yangtze River Delta region, is also the region with
      higher population density and richer economy. The worst natural environment
      areas, Northwest and Tibetan Plateau, are also regions with lower population
      density and poorer economies.

PMID- 20049244
TI  - Mapping environmental dimensions of dengue fever transmission risk in the Aburra
      Valley, Colombia.
AB  - Dengue fever (DF) is endemic in Medellin, the second largest Colombian city, and
      surrounding municipalities. We used DF case and satellite environmental data to
      investigate conditions associated with suitable areas for DF occurrence in 2008
      in three municipalities (Bello, Medellin and Itagui). We develop spatially
      stratified tests of ecological niche models, and found generally good predictive
      ability, with all model tests yielding results significantly better than random
      expectations. We concluded that Bello and Medellin present ecological conditions
      somewhat different from, and more suitable for DF than, those of Itagui. We
      suggest that areas predicted by our models as suitable for DF could be considered
      as at-risk, and could be used to guide campaigns for DF prevention in these
      municipalities.

PMID- 20049245
TI  - Assessment of Japanese stimulant control law offenders using the Addiction
      Severity Index--Japanese version: comparison with patients in treatment settings.
AB  - The present study assessed problems in Japanese prisoners (inmates) who abused
      methamphetamine. Fifty-two male inmates were assessed in 2005-2007 using the
      Addiction Severity Index-Japanese version and compared with 55 male
      methamphetamine abusers in hospitals and recovery centers. The chi(2) and Mann
      Whitney-Wilcoxon tests showed that the inmates had a significantly lower
      education level, more frequently had full-time jobs, had more experience living
      with a sexual partner, and more frequently had a history of juvenile delinquency
      and criminal records than patients. Although psychiatric symptoms, such as
      depression, anxiety, and hallucinations, were not common among inmates, suicidal
      behavior and trouble controlling violence were common in both groups.

PMID- 20049246
TI  - Sudden unexpected death in alcohol misuse--an unrecognized public health issue?
AB  - Sudden arrhythmic cardiac death can occur in chronic misusers of alcohol. The
      only findings at post mortem are fatty liver and a negative or low blood alcohol.
      This is an under-recognized entity. Coroner's post mortems in a typical UK city
      were studied. Seven out of 1,292 (0.5%) post mortems were deemed to have died of
      alcohol associated arrhythmic death. Applying this study to the UK as a whole,
      alcohol related arrhythmic death or as we have termed it SUDAM (Sudden Unexpected
      Death in Alcohol Misuse) probably accounts for around 1,000 deaths, many of which
      are misattributed to other causes.

PMID- 20049247
TI  - Associations between area-level unemployment, body mass index, and risk factors
      for cardiovascular disease in an urban area.
AB  - INTRODUCTION: Cardiovascular Disease (CVD) has been linked to "neighbourhood"
      socioeconomic status (nSES), often operationalized as a composite index of
      aggregate income, occupation and education within predefined administrative
      boundaries. The role of specific, non-composite socioeconomic markers has not
      been clearly explained. It is also unclear whether the relationship between nSES
      and CVD varies according to sex. We sought to determine whether area-level
      unemployment (ALU) was associated with CVD risk, and whether this association
      differed by sex. METHODS: 342 individuals from the Montreal Neighbourhood Survey
      of Lifestyle and Health provided self-reported behavioural and socioeconomic
      information. A nurse collected biochemical and anthropometric data. ALU, a
      weighted average of the proportion of persons 15-years and older available for
      but without work, was measured using a Geographic Information System for a 250 m
      buffer centred on individual residence. Generalized Estimating Equations were
      used to estimate the associations between ALU, body mass index (BMI) and a
      cumulative score for total cardiometabolic risk (TCR). RESULTS: After confounder
      adjustments, the mean 4(th) minus 1(st) quartile difference in BMI was 3.19
      kg/m(2) (95% CI: 2.39, 3.99), while the prevalence ratio for the 4(th) relative
      to 1(st) quartile for TCR was 2.20 (95 % CI: 1.53, 3.17). Sex interacted with
      ALU; women relative to men had greater mean 3.97 kg/m(2) (95% CI: 2.08, 5.85) BMI
      and greater mean TCR 1.51 (95% CI: 0.78, 2.90), contrasted at mean ALU.
      CONCLUSIONS: Area-level unemployment is associated with greater CVD risk, and
      this association is stronger for women.

PMID- 20049248
TI  - Deadly partners: interdependence of alcohol and trauma in the clinical setting.
AB  - Trauma is the leading cause of death for Americans aged 1 to 45. Over a third of
      all fatal motor vehicle collisions and nearly eighty percent of completed
      suicides involve alcohol. Alcohol can be both a cause of traumatic injury as well
      as a confounding factor in the diagnosis and treatment of the injured patient.
      Fortunately, brief interventions after alcohol-related traumatic events have been
      shown to decrease both trauma recidivism and long-term alcohol use. This review
      will address the epidemiology of alcohol-related trauma, the influence of alcohol
      on mortality and other outcomes, and the role of prevention in alcohol-related
      trauma, within the confines of the clinical setting.

PMID- 20049249
TI  - Very low dose fetal exposure to Chernobyl contamination resulted in increases in
      infant leukemia in Europe and raises questions about current radiation risk
      models.
AB  - Following contamination from the Chernobyl accident in April 1986 excess infant
      leukemia (0-1 y) was reported from five different countries, Scotland, Greece,
      Germany, Belarus and Wales and Scotland combined. The cumulative absorbed doses
      to the fetus, as conventionally assessed, varied from 0.02 mSv in the UK through
      0.06 mSv in Germany, 0.2 mSv in Greece and 2 mSv in Belarus, where it was
      highest. Nevertheless, the effect was real and given the specificity of the
      cohort raised questions about the safety of applying the current radiation risk
      model of the International Commission on Radiological Protection (ICRP) to these
      internal exposures, a matter which was discussed in 2000 by Busby and Cato and
      also in the reports of the UK Committee examining Radiation Risk from Internal
      Emitters. Data on infant leukemia in the United Kingdom, chosen on the basis of
      the cohorts defined by the study of Greece were supplied by the UK Childhood
      Cancer Research Group. This has enabled a study of leukemia in the combined
      infant population of 15,466,845 born in the UK, Greece, and Germany between 1980
      and 1990. Results show a statistically significant excess risk RR = 1.43 (95% CI
      1.13 < RR < 1.80 (2-tailed); p = 0.0025) in those born during the defined peak
      exposure period of 01/07/86 to 31/12/87 compared with those born between 01/01/80
      and 31/12/85 and 01/01/88 and 31/12/90. The excess risks in individual countries
      do not increase monotonically with the conventionally calculated doses, the
      relation being biphasic, increasing sharply at low doses and falling at high
      doses. This result is discussed in relation to fetal/cell death at higher doses
      and also to induction of DNA repair. Since the cohort is chosen specifically on
      the basis of exposure to internal radionuclides, the result can be expressed as
      evidence for a significant error in the conventional modeling for such internal
      fetal exposures.

PMID- 20049250
TI  - Examining the dynamic association of BMI and mortality in the Framingham Heart
      Study.
AB  - Based on the 40-year follow-up of the Framingham Heart Study (FHS), we used
      logistic regression models to demonstrate that different designs of an
      observational study may lead to different results about the association between
      BMI and all-cause mortality. We also used dynamic survival models to capture the
      time-varying relationships between BMI and mortality in FHS. The results
      consistently show that the association between BMI and mortality is dynamic,
      especially for men. Our analysis suggests that the dynamic property may explain
      part of the heterogeneity observed in the literature about the association of BMI
      and mortality.

PMID- 20049251
TI  - Toxicological assessment of toxic element residues in swine kidney and its role
      in public health risk assessment.
AB  - In order to ensure the safety of consumers in Serbia the prevalence of toxic
      elements (As, Cd, Hg, Pb) in swine kidney collected from three different areas in
      Serbia (n = 90) was determined by atomic absorption spectrometry. Also, in order
      to find information on the effects of accumulation of toxic elements on swine
      kidney, pathohistological examination of the kidneys was performed. The presence
      of mercury was found in 33.3% of kidney samples in the range of 0.005-0.055
      mg/kg, while the presence of cadmium was detected less often (27.7%) but in
      larger amounts (0.05-1.23 mg/kg). The presence of arsenic was found only in one
      sample, while no lead was found. The results of the metal-to-metal correlation
      analysis supported there were the result of different sources of contamination.
      Pathohistological examination of kidneys confirms tubulopathies with oedema and
      cell vacuolization. In addition, haemorrhages and necrosis of proximal kidney
      tubule cells were found. This study demonstrates that toxic elements in Serbian
      slaughtered pigs are found at levels comparable to those reported in other
      countries, and consequently the levels reported in this study do not represent a
      concern from a consumer safety point of view. The lack of a strong correlation
      between histopathological changes and the incidence of toxic elements found in
      this study might be explained as the result of synergism among toxic elements and
      other nephrotoxic compounds which enhance the toxicity of the individual toxins
      even at the relatively low mean concentrations observed in this study.

PMID- 20049252
TI  - Effect of Medicaid coverage of tobacco-dependence treatments on smoking
      cessation.
AB  - Smoking cessation aids (nicotine replacement products and anti-depressant
      medication) have been proven to double quitting rates compared to placebo in
      several randomized controlled trials. But the high initial cost of cessation aids
      might create a financial barrier to cessation for low-income smokers. In the
      U.S., Medicaid provides health insurance coverage to low-income people, and in
      some states covers smoking cessation products. This paper uses nationally
      representative data of the U.S. to examine how the Medicaid coverage of cessation
      aids affect smoking behavior. The results indicate the Medicaid coverage of
      cessation products is positively associated with successful quitting among women
      aged 18-44.

PMID- 20049253
TI  - Alcoholism and intimate partner violence: effects on children's psychosocial
      adjustment.
AB  - It is widely recognized that alcoholism and relationship violence often have
      serious consequences for adults; however, children living with alcoholic parents
      are susceptible to the deleterious familial environments these caregivers
      frequently create. Given the prevalence of IPV among patients entering substance
      abuse treatment, coupled with the negative familial consequences associated with
      these types of behavior, this review explores what have been, to this point, two
      divergent lines of research: (a) the effects of parental alcoholism on children,
      and (b) the effects of children's exposure to intimate partner violence. In this
      article, the interrelationship between alcoholism and IPV is examined, with an
      emphasis on the developmental impact of these behaviors (individually and
      together) on children living in the home and offers recommendations for future
      research directions.

PMID- 20049254
TI  - Seasonal and spatial variations of indoor pollen in a hospital.
AB  - The airborne indoor pollen in a hospital of Badajoz (Spain) was monitored over
      two years using a personal Burkard sampler. The air was sampled in four places
      indoors-one closed room and one open ward on each of the ground and the third
      floors-and one place outdoors at the entrance to the hospital. The results were
      compared with data from a continuous volumetric sampler. While 32 pollen types
      were identified, nearly 75% of the total counts were represented by just five of
      them. These were: Quercus, Cupressaceae, Poaceae, Olea, and Plantago. The average
      indoor concentration was 25.2 grains/m(3), and the average indoor/outdoor ratio
      was 0.27. A strong seasonal pattern was found, with the highest levels in spring
      and winter, and the indoor concentrations were correlated with the outdoor one.
      Indoor air movement led to great homogeneity in the airborne pollen presence: the
      indoor results were not influenced by whether or not the room was isolated, the
      floor level, or the number of people in or transiting the site during sampling.
      The presence of ornamental vegetation in the area surrounding the building
      affected the indoor counts directly as sources of the pollen.

PMID- 20049255
TI  - An exploratory study of diabetes in a First Nation community with respect to
      serum concentrations of p,p'-DDE and PCBs and fish consumption.
AB  - This study examined the association between self-reported diabetes, fish
      consumption and serum levels of organochlorines in a First Nation community. One
      quarter of the 101 participants reported diabetes. Serum PCBs, but not p,p'-DDE,
      were positively correlated to consumption frequency of total fish, walleye and
      pike, but not trout. Reported diabetes was positively associated to p,p'-DDE and
      some PCB congeners. Odds Ratios (OR) for reported diabetes for those in the upper
      75th percentile for serum p,p'-DDE compared to the others were 3.5 (95% CI 1
      13.8) and 6.1 (95% CI 1.4-27.3) (weight wet and lipid-standardized values,
      respectively) and for total sum of PCBs: 4.91 (95% CI 1.4-19.0) and 5.51 (95% CI
      1.3-24.1). For participants who were in the upper 50th percentile for trout and
      white fish intake, reported diabetes was respectively 6 and 4 times lower
      compared to the others. These findings support the hypothesis that environmental
      exposure to elevated p,p'-DDE and PCBs is associated with increased risk of
      diabetes. Consumption of trout and white fish may be beneficial to reduce risk.

PMID- 20049256
TI  - Geo-relationship between cancer cases and the environment by GIS: a case study of
      Trabzon in Turkey.
AB  - Cancer is an important health issue in Turkey because it ranks as the second
      cause of death in the country. Examination of the relationships between the
      distribution of cancer cases and geo-environmental factors is significant in
      determining the causes of cancer. In this study, GIS were used to provide data
      about the distribution of cancer types in Trabzon province, Turkey. To determine
      the cancer occurrence density, the cancer incidence rates were calculated
      according to local census data, then a cancer density map was produced, and
      correlations between cancer types and geographical factors were examined.

PMID- 20049257
TI  - Externalities from alcohol consumption in the 2005 US National Alcohol Survey:
      implications for policy.
AB  - A subsample (n = 2,550) of the 2005 US National Alcohol Survey of adults was used
      to estimate prevalence and correlates of six externalities from alcohol abuse-
      family problems, assaults, accompanying intoxicated driver, vehicular accident,
      financial problems and vandalized property--all from another's drinking. On a
      lifetime basis, 60% reported externalities, with a lower 12-month rate (9%).
      Women reported more family/marital and financial impacts and men more assaults,
      accompanying drunk drivers, and accidents. Being unmarried, older, white and ever
      having monthly heavy drinking or alcohol problems was associated with more
      alcohol externalities. Publicizing external costs of drinking could elevate
      political will for effective alcohol controls.

PMID- 20049258
TI  - Access to health care and religion among young American men.
AB  - In order to elucidate cultural correlates of utilization of primary health
      services by young adult men, we investigated religion in which one was raised and
      service utilization. Using data from a national survey we tested the hypothesis
      that religion raised predicts access to and utilization of a regular medical care
      provider, examinations, HIV and other STD testing and counseling at ages 18-44
      years in men born between 1958 and 1984. We also hypothesized that religion
      raised would be more predictive of utilization for Hispanic Americans and non
      Hispanic Black Americans than for non-Hispanic White Americans. The study
      included a national sample of 4276 men aged 18-44 years. Descriptive and
      multivariate statistics were used to assess the hypotheses using data on religion
      raised and responses to 14 items assessing health care access and utilization.
      Compared to those raised in no religion, those raised mainline Protestant were
      more likely (p < 0.01) to report a usual source of care (67% vs. 79%), health
      insurance coverage (66% vs. 80%) and physical examination (43% vs. 48%). Religion
      raised was not associated with testicular exams, STD counseling or HIV testing.
      In multivariate analyses controlling for confounders, significant associations of
      religion raised with insurance coverage, a physician as usual source of care and
      physical examination remained which varied by race/ethnicity. In conclusion,
      although religion is a core aspect of culture that deserves further study as a
      possible determinant of health care utilization, we were not able to document any
      consistent pattern of significant association even in a population with high
      rates of religious participation.

PMID- 20049259
TI  - Erythroderma: review of a potentially life-threatening dermatosis.
AB  - Erythroderma, or generalized exfoliative dermatitis, is a disease characterized
      by erythema and scaling of greater than 90% of the body's surface. The resultant
      dysmetabolism is potentially life threatening. A detailed history is to identify
      and treat the underlying cause of this dermatitis. We present two cases of
      erythroderma in African patients and review this important disease.

PMID- 20049260
TI  - Current concepts in the pathogenesis of psoriasis.
AB  - Psoriasis is a multi-factorial skin disease with a complex pathogenesis. Various
      factors which have been suggested to play a key role in the pathogenesis are T
      cells, antigen presenting cells (APC's), keratinocytes, Langerhans' cells,
      macrophages, natural killer cells, an array of Th1 type cytokines, certain growth
      factors like vascular endothelial growth factor (VEGF), keratinocyte growth
      factor (KGF), and others. It has been hypothesized that the disease starts with
      the activation of T cell by an unknown antigen, which leads to secretion of an
      array of cytokines by activated T cells, inflammatory cells, and keratinocytes.
      The characteristic lesion of psoriasis is due to the hyper-proliferation of the
      keratinocyte. Activated Langerhans' cells migrate from skin to lymph nodes
      presenting the antigen to nodal naive T cells (cells that have not been activated
      by antigen previously). The T cells activated by non-antigen-dependent mechanism
      may, however, become antigen-specific memory cells that react with a cross
      reactive auto-antigen such as keratin (molecular mimicry). The genetic background
      of the disease may be suggested from the fact that concordance rate is 63-73% in
      monozygotic twins, as compared to 17-20% in dizygotic twins. Several disease
      susceptibility loci have been suggested as predisposing factors, PSORS1-PSORS9.

PMID- 20049261
TI  - Study of total antioxidant status and glutathione peroxidase activity in Tunisian
      vitiligo patients.
AB  - BACKGROUND: Vitiligo affects one to two percent of the word population. Its
      pathogenesis has not been clarified yet. Multiple mechanisms such as autoimmune,
      neuronal, endocrine and oxidative stress resulting from unbalanced antioxidant
      defense system have been proposed. AIMS: Our purpose was to study the total
      antioxidant status and glutathione peroxidase activity in Tunisian vitiligo
      patients with or without diabetes or dysthyroidism. MATERIALS AND METHODS: We
      studied 60 vitiligo patients and 62 healthy controls. The sex ratio male/female
      in vitiligo patients was (27/33 = 0.81). Patients with vitiligo were divided into
      three groups, according to the association with diabetes or dysthyroidism. The
      total antioxidant status (TAS), glutathione peroxidase activity (GPX activity)
      was evaluated by adaptable methods using Kits. RESULTS AND CONCLUSION: The
      generalized vitiligo was the most frequent type (35 patients versus 25 of focal
      ones). All patients having vitiligo showed low levels of TAS: 0.85 +/- 0.7 and
      low GPX activity: 45 +/- 0.6, as compared to the control group: 1.40 +/- 0.12
      mmol/L; 49 +/- 1.8 U/L, (p < 0.01), for TAS and GPX, respectively. The
      association of low TAS and GPX activities was more pronounced in diabetic
      vitiligo patients than in dysthyroid vitiligo patients. This study demonstrated
      that antioxidant processes depletion (low TAS and low GPX activity) is clearly
      involved with vitiligo in Tunisian patients, regardless of the association of the
      disease with diabetes or dysthyroidism.

PMID- 20049262
TI  - Alopecia areata is not associated with Helicobacter pylori.
AB  - BACKGROUND: Alopecia areata (AA) is an immune-mediated form of hair loss that
      occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has been
      associated with many extra-digestive dermatological conditions. The causal
      relation between alopecia areata and Helicobacter pylori is discussed in this
      study. MATERIALS AND METHODS: We have screened for the presence of H. pylori in
      patients with AA, in order to determine any potential role in its patho
      physiology. We have prospectively studied 31 patients with alopecia areata and 24
      healthy volunteers of similar gender, for the presence of H. pylori stool antigen
      (HpSAg). RESULTS: Optical density values for H. pylori infection was positive in
      18 of the 31 patients evaluated (58.1%), while in 13 patients, the values did not
      support H. pylori infection (41.9%). In the control group, 10 of the 24 (41.7%)
      had positive results. Within the group of alopecia areata, there was no
      significant difference between HpSAg positive and negative patients. CONCLUSIONS:
      The results have shown that a relation between Helicobacter pylori and alopecia
      areata is not supported. We advise that H. pylori detection need not to be
      included in the laboratory work up of alopecia areata.

PMID- 20049263
TI  - Serum leptin, atherogenic lipids and glucose levels in patients with skin tags.
AB  - AIM: To investigate the relationship between serum leptin, atherogenic lipid and
      glucose levels in patients with skin tags and healthy controls. MATERIALS AND
      METHODS: A total of 58 patients, with at least three skin tags, aged 24 to 85
      years, and 31 healthy controls aged 30 to 70 years, were examined in the present
      study. The subjects in all the groups were selected with statistically similar
      Body Mass Index (BMI). Fasting concentrations of plasma glucose, serum lipids
      including triglyceride, total cholesterol, and high-density lipoprotein
      cholesterol (HDL) and low-density lipoprotein cholesterol (LDL), HbA1c, and
      leptin were measured by enzyme-linked immunosorbent assay (ELISA). In addition,
      serum LDL level was calculated using Friedewald's formula. RESULTS: There was no
      significant difference in age, sex, BMI, HbA1c, triglyceride, HDL and leptin
      levels between the groups. Skin tags group showed significantly higher levels of
      total cholesterol and LDL, when compared with the healthy controls groups (P <
      0.01). In addition, regression analysis showed that leptin level was positively
      correlated to serum triglyceride level (r = 0.265, P = 0.044). CONCLUSION: Total
      cholesterol and LDL serum levels should be controlled in patients with skin tags.
      On the other hand, glucose, leptin and HbA1c serum levels may not be as important
      as is being considered in recent times.

PMID- 20049264
TI  - Breast cancer, dermatofibromas and arsenic.
AB  - BACKGROUND: Dermatofibromas are common benign tumors in women, and breast cancer
      is the most common malignancy in women. The aim of this study is to determine if
      there is any relationship between the two conditions. MATERIALS AND METHODS: Five
      patients with dermatofibromas and 10 control patients (two groups) had their skin
      biopsies measured for arsenic by inductively coupled mass spectrometry. Fifty
      randomly selected patients with breast cancer and 50 control patients were
      examined for the presence of dermatofibromas. RESULTS: The dermatofibromas were
      found to have an arsenic concentration of 0.171 micrograms/gram, compared with
      0.06 and 0.07 micrograms/gram of the two control groups. Forty-three out of 50
      patients with breast cancer had dermatofibromas and 32/50 patients with breast
      cancer had multiple dermatofibromas, compared to 10/50 control patients with
      dermatofibromas and only 1/50 with multiple dermatofibromas. CONCLUSIONS: Arsenic
      is important in the development of dermatofibromas and dermatofibromas represent
      a reservoir and important sign of chronic arsenic exposure. Dermatofibromas
      represent an important sign for women at risk for breast cancer, and arsenic may
      represent the cause of the majority of cases of breast cancer.

PMID- 20049265
TI  - Epidemic of hand, foot and mouth disease in West Bengal, India in August, 2007: a
      multicentric study.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) is caused mostly by
      Coxsackievirus A16 (CA16) and enterovirus 71 (EV71). Epidemic of HFMD has
      occurred in India only once in Kerala in 2003. We report here a recent outbreak
      of HFMD in three districts of West Bengal, India. MATERIALS AND METHODS: A case
      detection system developed with 1) three private clinics in three districts; two
      at Howrah and one at Hooghly, 2) Pediatrics Department of two medical colleges in
      Kolkata, 3) 12 practioners of these three districts with 4) a central referral
      center at Department of Dermatology, NRS Medical College, Kolkata where all cases
      from this system were confirmed by a single observer. Pediatric Dermatology unit
      of the Institute of Child Health, Kolkata was another independent unit. RESULTS:
      A total of 38 cases of HFMD were reported till 08.10.07. Age group ranged from 12
      months to 12 years (mean 40.76 months, SD 29.49). Males were slightly higher than
      females (M:F - 21:17). Disease was distributed mostly over buttocks, knees,
      hands, feet - both dorsum and palmar or the plantar surface and the oral mucosa.
      Highest severity noted over the buttocks and the knee. Healing time for skin
      lesions was 6-13 days (mean 9.13 days, SD 1.93). Oral lesions were found in 33
      (86.8%) cases. CONCLUSION: This outbreak far away from the initial one confirmed
      regular outsourcing of the virus with possibilities of future epidemics. Also the
      fact that EV71 induced epidemic is on rise in this part of globe is alarming for
      India. We hope this early report will be of help for strategic planning for a
      better management of the disease and prevention of dreaded neurological
      complications in India.

PMID- 20049266
TI  - Detection of R576 interleukin-4 receptor an allele gene, serum interleukin-4, and
      eosinophilic cationic protein in atopic dermatitis patients.
AB  - Atopic dermatitis (AD) is a chronic pruritic skin disease. It results from a
      complex interplay between strong genetic and environmental factors. The aim of
      this work was to study some biochemical markers of the dermatosis. This included
      detection of R576 interleukin-4 receptor alpha allele gene. Twenty five patients
      with AD and 25 controls participated in this study.

PMID- 20049267
TI  - Oxidant/antioxidant status in obese adolescent females with acne vulgaris.
AB  - BACKGROUND AND OBJECTIVES: Acne vulgaris is a distressing skin condition, which
      can carry with it significant psychological disability. Oxidant/antioxidant
      imbalance leads to increased production of free radicals, that cause many
      diseases. Some nutrients, along with systemic oxidative stress, have been
      implicated in acne vulgaris. The goal of the present study was to assess oxidant
      and antioxidant status in correlation with the incidence of acne vulgaris in
      adolescent obese females. MATERIALS AND METHODS: A total of 60 adolescent females
      (age 16-22 years) were divided into four groups (15 each) as follows: The first
      included obese females with acne; the second included obese females without acne;
      the third included non obese with acne and the fourth included non obese without
      acne. Fasting serum Malondialdehyde (MDA), beta-carotene, and Vitamins A, E, and
      C were measured. In addition, platelet monoamineoxidase (MAO), and erythrocyte
      catechol-o-methyltransferase (COMT) activities were determined. RESULTS: It was
      found that serum MDA was statistically significantly decreased in obese and non
      obese subjects with acne, as compared to those without acne (P<0.05, P<0.001)
      respectively. In contrast, the levels of beta-carotene, vitamins A, E and C and
      the activity of MAO were significantly decreased in the obese and non obese with
      acne, as against the obese and non obese without acne. INTERPRETATION: In obese
      subjects, increased fat content facilitates free radical production and lipid
      peroxidation, as indicated by increased MDA level, which is scavenged by the
      antioxidant vitamins. The decreased activity of MAO may be inhibited by free
      radicals and this causes psychological depression in adolescents. However there
      were non significant changes in the activity of COMT among the studied groups.
      CONCLUSION: The nutritional factors and a weakened antioxidant defense system may
      interplay, to increase the risk of psychological sequelae in acne vulgaris.

PMID- 20049268
TI  - A study comparing chemical peeling using modified Jessner's solution and 15%
      trichloroacetic Acid versus 15% trichloroacetic acid in the treatment of melasma.
AB  - BACKGROUND: Melasma is a symmetric progressive hyperpigmentation of the facial
      skin that occurs in all races but has a predilection for darker skin phenotypes.
      Depigmenting agents, laser and chemical peeling as classic Jessner's solution,
      modified Jessner's solution and trichloroacetic acid have been used alone and in
      combination in the treatment of melasma. OBJECTIVES: The aim of the study was to
      compare the therapeutic effect of combined 15% Trichloroacetic acid (TCA) and
      modified Jessner's solution with 15% TCA on melasma. MATERIALS AND METHODS:
      Twenty married females with melasma (epidermal type), with a mean age of 38.25
      years, were included in this study. All were of skin type III or IV. Fifteen
      percent TCA was applied to the whole face, with the exception of the left malar
      area to which combined TCA 15% and modified Jessner's solution was applied.
      RESULTS: Our results revealed statistically highly significant difference between
      MASI Score (Melasma Area and Severity Index) between the right malar area and the
      left malar area. CONCLUSION: Modified Jessner's solution proved to be useful as
      an adjuvant treatment with TCA in the treatment of melasma, improving the results
      and minimizing postinflammatory hyperpigmentation.

PMID- 20049269
TI  - Malignant transformation of actinic keratoses to squamous cell carcinoma in an
      albino.
AB  - A 25-year-old male, who was a known case of oculocutaneous albinism presented to
      us with right inguinal swellings of six months' duration. He gave a preceding
      history of a similar lump in the right thigh, which was excised at the Chennai
      Government Hospital. He was diagnosed to have oculocutaneous albinism with
      actinic keratoses, with multiple squamous cell carcinomas (with metastatic
      deposits in the right inguinal region) and cutaneous horns. The case is reported
      to highlight preventive aspects in the management of albinos.

PMID- 20049270
TI  - Disseminated cysticercosis with huge muscle hypertrophy.
AB  - Cysticercosis is caused by cysticercus cellulose, which is the larva of Taenia
      solium, the pork tapeworm. The larvae are carried in the blood stream after
      penetrating the walls of the alimentary tract and they lodge in different tissues
      like the skin, skeletal muscles, brain, fundus and heart, to cause disseminated
      cysticercosis. Cases of disseminated cysticercosis have rarely been reported in
      the literature. They may inhabit the muscles and cause muscular hypertrophy,
      which, at times, may assume gross proportions. Morbidity is usually caused by the
      involvement of the central nervous system or the eyes.

PMID- 20049271
TI  - Elephantiasis of the external genitalia: a sequel to cutaneous tuberculosis.
AB  - Tuberculosis continues to be an important public health problem and cutaneous
      tuberculosis constitutes a minor proportion of extra pulmonary manifestations of
      tuberculosis. Elephantiasis of the external genitalia, as a sequel to cutaneous
      tuberculosis, in a 40-year-old diabetic lady is being reported for its rarity.
      The patient also had lesions of healed scrofuloderma of 27 years' duration, in
      both axillae, with residual pedunculated nodules.

PMID- 20049272
TI  - Late reaction, persistent reaction and doubtful allergic reaction: the problems
      of interpretation.
AB  - The standard method of patch test reading is to read the test site for any
      positive allergy at 48 hr and then again at 72/96 hr. A late reading on the
      seventh day is also advised to exclude the irritant reaction (IR) and to notice
      some delayed development of allergic reaction. However, multiple visits are often
      difficult for the patient; therefore, this late reading is sometimes omitted.
      Here a case of plantar hyperkeratosis, due to allergic contact dermatitis, is
      reported with some insight into interpretation of the patch test. The patient
      showed delayed patch test reaction to formaldehyde and colophony, which has never
      been reported before.

PMID- 20049273
TI  - Myxoid neurothekeoma: a rare soft tissue tumor of hand in a 5 month old infant.
AB  - Myxoid Neurothekeoma is a rare benign nerve sheath tumor, commonly seen in young
      females. Patients usually present with a small nodule in different anatomical
      sites, commonly involving the face and the upper limb. We present the case of a
      five-month-old boy, who presented with a nodule on the left thumb. Punch biopsy
      and immunostaining confirmed the diagnosis of myxoid neurothekeoma. We believe
      this is the first reported case of myxoid neurothekeoma below 12 months of age.

PMID- 20049274
TI  - Childhood herpes zoster: a clustering of ten cases.
AB  - Herpes zoster occurs due to reactivation of the latent varicella zoster virus and
      is usually a disease of the elderly. Childhood herpes zoster is believed to be
      rare, though recent studies suggest increasing incidence in children. Here we
      report ten cases of childhood herpes zoster, seven of which occurred within a
      short span of six months, at a tertiary care level hospital in Pokhara, Nepal.
      Only three of the ten children reported previous history of varicella infection
      and none was immunized against varicella. Though childhood herpes zoster
      accounted for less than 1% of the total zoster cases in the past, recent reports
      show an increase in the number of cases in apparently healthy children. So far,
      no studies have been done linking childhood herpes zoster with HIV, though there
      are many studies linking it with other immunocompromised conditions.

PMID- 20049275
TI  - Generalized eruptive syringomas.
AB  - Generalized eruptive syringoma is a rare clinical presentation of a benign
      adnexal tumor that derives from the intraepidermal portion of the eccrine sweat
      ducts. It presents as successive crops of small flesh-colored papules on the
      anterior body surfaces. It generally occurs in the peripubertal period. Treatment
      of this benign condition is cosmetic only. A case of a 28-year-old female with an
      eight-year history of eruptive syringoma is presented.

PMID- 20049276
TI  - Multiple smooth muscle hamartoma: case report and review of the literature.
AB  - Smooth muscle hamartoma (SMH) is a proliferative disorder of cells originating
      from muscle cells. It is a benign tumoral mass that usually presents as a single
      congenital skin-colored and hypertrichotic plaque involving the trunk and
      extremities. Multiple SMHs have rarely been reported in the literature. We
      describe the case of a seven-month-old girl with multiple SMHs located over the
      back and arm areas. The diagnosis was confirmed by biopsy and immunohistochemical
      (IHC) staining. She had no cerebral or skeletal abnormalities and her growth and
      development were normal.

PMID- 20049277
TI  - Multiple cutaneous leiomyomas: pain relief with pulsed hysocine butyl bromide.
AB  - A 35-year-old male patient presented to our outpatient department, complaining of
      multiple, raised skin lesions on the forehead and back, associated with
      intermittent pain, especially on exposure to cold. A diagnosis of cutaneous
      leiomyoma (type 2 segmental) was made, which was confirmed by skin biopsy. The
      patient was started on a trial of pulsed Hyoscine Butyl bromide tablets,
      following which the patient had significant relief from pain associated with the
      lesions.

PMID- 20049278
TI  - Crusted Piloleiomyoma with mental retardation: a rare association.
AB  - Piloleiomyoma is an uncommon benign smooth muscle neoplasm arising from arrector
      pili muscle. It is clinically defined by the presence of solitary or multiple
      reddish brown, dome-shaped, smooth papules or nodules, ranging in size from a few
      millimeters to a centimeter. The patients are otherwise healthy; but mental
      retardation developing in some patients with multiple Piloleiomyomas has been
      emerging as an intriguing matter for analysis by the scientists. In this case
      report, a mentally retarded patient with Piloleiomyoma is described, who, besides
      the characteristic smooth and dome-shaped lesions on the anterolateral aspect of
      the dorsum of the right foot, had developed crusting on one of the largest
      lesions. The histopathological features were consistent with Piloleiomyoma. The
      occurrence of Piloleiomyoma in a mentally retarded child and its unusual crusted
      nature has been rarely reported. The association between Piloleiomyoma and mental
      retardation is further stressed in this case report.

PMID- 20049279
TI  - Intravenous immunoglobulin in dermatology.

PMID- 20049280
TI  - Hirsutism in Kashmir: an etiological study.
AB  - BACKGROUND: Hirsutism refers to the presence of terminal hairs at the body sites
      under androgenic control. Various factors, including genetic makeup and hormonal
      status, influence the rate and pattern of hair growth at these sites. PURPOSE: To
      study the pattern of hirsutism in Kashmir. MATERIALS AND METHODS: Thirty five
      consecutive patients of hirsutism were included in the study. After detailed
      history taking, physical examination and relevant investigations, scoring of
      hirsutism was done using the Ferriman Gallwey (FG) scoring system. FINDINGS: The
      FG score ranged from 10-34. Twenty patients had associated menstrual
      abnormalities. Polycystic ovarian syndrome (PCOS) was diagnosed in four patients,
      hypothyroidism in two and congenital adrenal hyperplasia (CAH) in one. The rest
      of the patients had idiopathic hirsutism. CONCLUSION: Idiopathic hirsutism was
      the most common category, whilst PCOS, hypothyroidism and CAH were also seen.

PMID- 20049281
TI  - Impactitis: the impact factor myth syndrome.
AB  - BACKGROUND: In the early 1960s, Eugene Garfield and Irving Sher created the
      journal impact factor to help select journals for the Science Citation Index
      (SCI). Today it has become a widespread subject of controversy even for Garfield,
      the man who created it who is quoted saying "Impact Factor is not a perfect tool
      to measure the quality of articles but there is nothing better and it has the
      advantage of already being in existence and is, therefore, a good technique for
      scientific evaluation". The use of the term "impact factor" has gradually
      evolved, especially in Europe, to include both journal and author impact. This
      ambiguity often causes problems. It is one thing to use impact factors to compare
      journals and quite another to use them to compare authors. Journal impact factors
      generally involve relatively large populations of articles and citations.
      Individual authors, on average, produce much smaller numbers of articles.
      OBJECTIVES: Impact factor, an index based on the frequency with which a journal's
      articles are cited in scientific publications, is a putative marker of journal
      quality. However, empiric studies on impact factor's validity as an indicator of
      quality are lacking. The authors try to evaluate and highlight the validity of
      Impact Factors and its significance as a tool of assessment for scientific
      publications. METHODS: Analysis of the several reports in literature and from
      their own point of view. CONCLUSION: A journal's impact factor is based on 2
      elements: the numerator, which is the number of citations in the current year to
      any items published in a journal in the previous 2 years, and the denominator,
      which is the number of substantive articles (source items) published in the same
      2 years. The impact factor could just as easily be based on the previous year's
      articles alone, which would give an even greater weight to rapidly changing
      fields.

PMID- 20049282
TI  - Autologous serum skin test.

PMID- 20049283
TI  - The efficacy of topical diphencyprone in the treatment of alopecia areata.

PMID- 20049284
TI  - Dhat syndrome: a reappraisal.

PMID- 20049285
TI  - Sarcoidosis with photosensitive lesions: a rare variant.

PMID- 20049286
TI  - Triple combination of hydroquinone, tretinoin and mometasone furoate with
      glycolic acid peels in melasma.

PMID- 20049287
TI  - Montelukast does not inhibit the late phase reaction in Parthenium dermatitis.

PMID- 20049288
TI  - An 11-year-old boy with dark skin, swallowing difficulty and absence of tears.

PMID- 20049289
TI  - New poverty line and growth chart bring forth sharp inequalities in the Indian
      population.

PMID- 20049290
TI  - Training in clinical research in India: potential and challenges.

PMID- 20049291
TI  - National rural health mission: time to take stock.

PMID- 20049292
TI  - Period prevalence and sociodemographic factors of hypertension in rural
      maharashtra: a cross-sectional study.
AB  - BACKGROUND: Hypertension is most common cardiovascular disease and it account for
      large proportion of all cardiovascular deaths and disability worldwide. RESEARCH
      QUESTIONS: What is the level of prevalence of hypertension in rural area? What
      are the soociodemographic factors associated with hypertension? OBJECTIVES: To
      find out prevalence of hypertension in rural area. STUDY DESIGN: A community
      based cross-sectional study setting: Rural Health Training Centre Paithan, field
      practice area of govt. medical college Aurangabad, Maharashtra. PARTICIPANTS:
      1297 persons aged 19 years and above. STUDY PERIOD: June 2005 to December 2006.
      MATERIALS AND METHODS: A house-to-house survey was conducted by the author
      himself, interviewed the participants by systematic random sampling method, using
      pretested structured standard questionnaire. Two independent blood pressure (BP)
      readings were taken in sitting position by visiting each participant at their
      home. Hypertension was defined as systolic BP more than or equal to 140 mm of Hg
      or diastolic BP more than or equal to 90 mm of Hg or those individuals currently
      taking antihypertensive treatment. STATISTICAL TESTS: Percentiles, Chi Square
      test, Chi-Square for linear trend, multiple logistic regression analysis on SPSS
      software Version 10. RESULTS: Overall prevalence of hypertension in the study
      subjects was 7.24%. Multiple logistic regression analysis identified various
      factors significantly associated with hypertension were age, sex, BMI, additional
      salt intake, smoking, DM, alcohol consumption, and higher socioeconomic status.
      CONCLUSIONS: The overall prevalence of hypertension in study subjects was 7.24%.

PMID- 20049293
TI  - Unmet family planning need: differences and levels of agreement between husband
      wife, haryana, India.
AB  - RESEARCH QUESTION: Is there agreement between husbands and wives regarding unmet
      need of family planning? HYPOTHESIS: The unmet need of family planning is
      perceived more by women then their husbands. OBJECTIVE: 1) To ascertain the unmet
      needs of family planning for husbands and wives. 2) To ascertain the level of
      agreement between husbands and wives regarding unmet needs of family planning.
      DESIGN: A cross-sectional survey SETTING: Dayalpur village in Intensive field
      practice area of Comprehensive Rural Health Services project (CRHSP), Ballabgarh,
      Haryana. STUDY PERIOD: July 2003- June 2005. PARTICIPANTS: included 200 married
      couples selected by simple random sampling. STATISTICAL ANALYSIS: Level of
      agreement between husbands and wives was analyzed using Kappa statistics.
      RESULTS: Unmet need for family planning was 11% (22 out of 200) for husbands and
      17.5% (35 out of 200) for wives. The difference was seen both in unmet need for
      spacing (M-3.5% vs. F-6%) as well as limiting family size (M-7.5% vs. F-11.5%).
      Overall, 93.5% concordance was observed amongst husbands and wives. In all the
      cases where disagreement was seen (6.5%), wives reported having unmet need for
      contraception whereas their husbands perceived none. The unadjusted Kappa
      statistic was 0.73 and prevalence adjusted Kappa was 0.88. CONCLUSION: Unmet need
      for family planning was significantly higher for wives compared to husbands.
      Despite high degrees of agreement amongst the couples, the nature of
      disconcordance reinforces the need for policy makers to take into account the
      perspective of men.

PMID- 20049294
TI  - Sleep deprivation predisposes gujarati Indian adolescents to obesity.
AB  - BACKGROUND AND AIM: Recent studies on various populations indicate that lack of
      sleep is one of the potential risk factors predisposing the youth to obesity.
      Since there is a significant rise in obesity among Indian youth and because
      research indicating the role of sleep in development of obesity among Indian
      population is scant, the current study was undertaken to assess the effect of
      sleep duration on adiposity among Gujarati Indian adolescents. MATERIALS AND
      METHODS: A randomized cross-sectional study was done on 489 voluntarily
      participating Indian adolescents in the age group of 16-19 years. Participants
      were grouped into two categories 1). Adequate Sleep Duration at Night (more than
      seven hours, ASDN) and 2) Inadequate Sleep Duration at Night (less than seven
      hours, IASDN) as reported by the participants. The participants were later
      assessed for adiposity in terms of BMI, BF %, FM, FMI and waist circumference,
      meal frequency per day and physical activity status. RESULTS: In both boys as
      well as girls, the BMI, BF%, FM and FMI were significantly lower in the ASDN
      group than the IASDN group. However, there was an insignificant difference in the
      meal frequency and physical activity status between the ASDN and IASDN group.
      CONCLUSION: Inadequate sleep duration increases adiposity among Gujarati Indian
      adolescents but further studies are required to find out the mechanisms through
      which sleep affects adiposity in this population.

PMID- 20049295
TI  - Prevalence of common ocular morbidities in adult population of aligarh.
AB  - AIMS AND OBJECTIVES: To determine the prevalence of common ocular morbidities
      (cataract, refractive errors, glaucoma, and corneal opacities) and their
      demographic and sociocultural correlates. SETTINGS AND DESIGN: The present cross
      sectional study was conducted in the field practice areas of the Department of
      Community Medicine, JNMC, AMU, Aligarh, for a period of one year, from September
      2005 to August 2006. MATERIALS AND METHODS: Systematic random sampling was done
      to select the required sample size. All adults aged 20 years and above in the
      selected households were interviewed and screened using a 6/9 illiterate 'E'
      chart. Those who could not read the 'E' chart were referred to the respective
      health training center for a complete eye examination by an ophthalmologist.
      STATISTICAL ANALYSIS: Chi- square test. RESULTS: The prevalence of visual
      impairment, low vision, and blindness, based on presenting visual acuity was
      13.0, 7.8, and 5.3%, respectively. The prevalence of cataract was 21.7%.
      Bilateral cataract was present in 16.9% of the population. Cataract was
      significantly associated with age, education, and fuel use. The prevalence of
      myopia, hypermetropia, and astigmatism was 11.5, 9.8, and 3.7%, respectively.
      Glaucoma was diagnosed in six patients, giving a prevalence rate of 0.9%. All the
      six patients of glaucoma were aged above 40 years. The prevalence of corneal
      opacity was 4.2%. CONCLUSION: There is a high prevalence of treatable or
      preventable morbidities such as cataract, refractive errors, and corneal opacity.

PMID- 20049296
TI  - An Epidemiological Study of Filariasis in a Village of District Datia, MP.
AB  - BACKGROUND: District Datia has been known to be endemic for filariasis. A number
      of cases have been reported in recent past. The present study was an
      epidemiological investigation carried out in village Barganya, Datia in the month
      of Sept 2004. AIMS AND OBJECTIVES: The objectives of this study were to confirm
      the epidemic in village Barganya and to study the causes of the present epidemic.
      MATERIALS AND METHODS: The study was a cross sectional study carried out through
      house to house survey, covering a population of 1512. RESULT: A total of 78
      clinically confirmed cases were reported. The study calculated a microfilarial
      rate of 6.9% and 1.65% in males and females respectively. The microfilarial
      density among confirmed cases ranged from 3.1 to 10.6 per 20 cmm. CONCLUSION: The
      study concluded that majority of the cases were males who worked in open field
      and there was a lack of proper management of these cases at village level.

PMID- 20049297
TI  - Sexual Practice and Perception of HIV/AIDS Amongst Men who have Sex with Men in
      Kolkata.
AB  - BACKGROUND AND OBJECTIVES: Men who have Sex with Men (MSM) are a vulnerable
      population and need special attention in the fight against the global pandemic of
      HIV/AIDS. A study was conducted in an MSM clinic to find out to their varied
      socio-demographic characteristics, their knowledge and attitude towards HIV/AIDS,
      and its association with their different sexual practices. MATERIALS AND METHODS:
      Descriptive, cross sectional study conducted in an MSM clinic in central Kolkata.
      RESULTS: A total of 108 MSM were studied over a period of six months. A majority
      (25%) were students, followed by drivers (22.2%), with mean age being 22.8 years.
      About 13.9% of them were illiterate and 30.6% of them married. A majority (75%)
      of the clients were initiated to first sexual act during adolescence. Most (44%)
      of them had indulged in sexual acts with two/three partners in the past one
      month. The most common form of sexual act was receptive anal sex (83.3%). The
      commonest reasons for indulging into such sexual acts with men were increased
      pleasure to have sex with men and increased sexual urge (38.9% and 27.8%) while
      19.4% performed such acts in an intoxicated state. Only 22.2% ever used condom in
      the last one month during sexual acts. Their knowledge and positive attitude
      towards HIV/AIDS increased significantly with increase in literacy status (P less
      than 0.01). Only 36 (33.3%) knew about HIV transmission through anal route while
      only 35.2% knew the correct method to use condom. Favorable sexual practices like
      using a condom or having fewer partners was more among the literates than the
      illiterates (P less than 0.05). Alarmingly 44.4% felt that one should have sex
      without a condom if his sex partner was extremely attractive, 88.9% felt that
      using a condom was not necessary if his partner was clean and hygienic, 69.4%
      felt that anal sex is for fun, so no condom is required while 43.5% felt getting
      HIV was a matter of bad luck. CONCLUSION: Proper IEC to promote condom use and
      promotion of safe sexual practice among MSM is the need of the hour.

PMID- 20049298
TI  - Prevalence of HIV/AIDS and Prediction of Future Trends in North-west Region of
      India: A six-year ICTC-based Study.
AB  - BACKGROUND: The study was conducted to analyze previous six-year prevalence data
      of HIV infection in the Northwest region of India and predict future trends for a
      couple of years. OBJECTIVES: The study was conducted to aid SACS and NACO to plan
      and arrange resources for the future scenario. MATERIALS AND METHODS: All the
      attendees of ICTC, Jaipur, from January 2002 to December 2007 were included and
      variables like age, sex, marital status, occupation, place of residence, pattern
      of risk behavior and HIV serostatus were studied. As per the strategy and policy
      prescribed by NACO, tests (E/R/S) were performed on the serum samples. Data was
      collected; compiled and analyzed using standard statistical methods. Future
      trends of HIV-prevalence in north-west India were anticipated. RESULTS: The
      overall positivity rates among attendees of ICTC, were found to be 12.2%
      (386/3161), 11.8% (519/4381), 11.1% (649/5867), 13% (908/6983), 14% (1385/9911)
      and 17.34% (1756/10133) in the years 2002, 2003, 2004, 2005, 2006 and 2007
      respectively. Future trends for the next couple of years depict further increase
      in prevalence without any plateau. CONCLUSION: Epidemiological studies should be
      carried out in various settings to understand the role and complex relations of
      innumerable behavioral, social and demographic factors, which will help,
      interrupt and control the transmission of HIV/ AIDS.

PMID- 20049299
TI  - A Cross-sectional Study to Determine Prevalence of Obesity in High Income Group
      Colonies of Gwalior City.
AB  - BACKGROUND: Obesity has become a major chronic disorder affecting the larger
      population more than any other disease in the world. OBJECTIVES: 1) To determine
      the prevalence of obesity in both sexes in persons aged 30 years and above. 2) To
      determine the relationship of epidemiological determinants on the obesity status
      in the study subjects. MATERIALS AND METHODS: The present study had been
      undertaken in literate high income group colonies of Gwalior city in which
      persons aged 30 years and above, in a family, were interviewed. A house-to-house
      survey method on a pre-designed, pre-tested structured questionnaire was used.
      Information regarding socio-demographic profile, eating habits and current health
      status were recorded. Anthropometric data regarding height, weight and blood
      pressure was also taken. The data was collected and analyzed using statistical
      software and chi square and proportional statistical test were applied. RESULTS:
      The study showed that 34.4% of males and 31.3 % of females, both aged 30years and
      above were either obese or over weight. There was a statistically significant
      difference noted in the likening of fried food and fast food between obese and
      overweight persons and persons with normal body mass index. CONCLUSIONS: It can
      be concluded from the present study that obesity is a chronic illness. Early
      detection of it can prevent various complications associated with it. BMI plays a
      crucial role in its early detection as it is simple to calculate and can even
      detect the pre-obesity stage in time.

PMID- 20049300
TI  - Profile of Clients Tested HIV Positive in a Voluntary Counseling and Testing
      Center of a District Hospital, Udupi.
AB  - BACKGROUND: The growing menace created by the HIV/AIDS (human immunodeficiency
      virus/acquired immunodeficiency syndrome) has alarmed not only the public health
      officials but also the general community. The Voluntary Counseling and Testing
      Centre (VCTC) services have begun as a cost-effective intervention in reversing
      this epidemic. OBJECTIVES: 1) To study the sociodemographic characteristics of
      HIV-positive clients and their risk behaviors. 2) To elucidate the reasons for
      their visit to the VCTC and know the problems anticipated by the clients after
      revealing their HIV-positive status. STUDY DESIGN: A cross-sectional record-based
      study. MATERIALS AND METHODS: The study was conducted in August 2007 among
      clients who tested positive for HIV in the VCTC of a district hospital in
      Karnataka from January to July 2007. RESULTS: Study included 249 individuals of
      whom 161 were males and rest 88 females. A high percentage of nonresponse
      regarding the pattern of risk behavior was noted among the subjects (males: 42.8%
      and females: 90.9%). Of the individuals who responded, 91 males (98.9%) and 6
      females (75.0%) had multiple heterosexual sex partners, while 1 male had
      homosexual partner. The figures in females show that two (25%) of them had a
      history of blood transfusion. The reason for visiting the VCTC were cited as some
      form of illness (33.3%), confirmation of test results (32.9%), family members
      diagnosed as HIV positive (12.9%) and 11.6% were referred from Directly Observed
      Treatment Scheme (DOTS) center. More than one-thirds of the sample population
      anticipated discrimination at the time of medical treatment. CONCLUSION: People
      have begun using VCTC services, which reflects a change in their attitude toward
      HIV. The study provides us a clue to formulate an effective approach to educate
      people as well as the health personnel who are thought of as one of the important
      sources of discrimination.

PMID- 20049301
TI  - Teenage pregnancy: a socially inflicted health hazard.
AB  - BACKGROUND: Early marriage and confinement are contributing factors to high
      maternal and perinatal mortality and morbidity. OBJECTIVE: To assess the
      magnitude of the problem of teenage pregnancy and its complications. MATERIALS
      AND METHODS: A hospital-based cohort study was undertaken over 4 months among
      women admitted to a rural hospital in West Bengal. The study cohort comprised of
      teenage mothers between 15-19 years old and a control cohort of mothers between
      20-24 years old. Data included demographic variables, available medical records,
      and complications viz. anemia, preterm delivery, and low birth weight. Anemia was
      defined as a hemoglobin level below 10 gm% during the last trimester of
      pregnancy, preterm delivery was defined as occurring within 37 weeks of
      gestation, and low birth weight was defined as babies weighing less than 2500
      grams at birth. RESULT: Teenage pregnancy comprised 24.17% of total pregnancies
      occurring in the hospital during the study period. The study group had 58
      subjects and the control group had 91 subjects. The prevalence of anemia was
      significantly higher (P<0.05) in the women in the teenage group (62.96%) than in
      the women in the control group (43.59%). However, severe anemia with a hemoglobin
      level below 8 gm% was only found in the control group. Preterm delivery occurred
      significantly more (P<0.001) in the study group (51.72%) than in the control
      group (25.88%). The incidence of low birth weight was significantly higher
      (P<0.0001) among the group of teenagers (65.52%) than among the women in the
      control group (26.37%). Not a single newborn was above 3 kg in the study group,
      while none were below 1.5 kg in the control group. The mean birth weight was 2.36
      kg in the study group and 2.74 kg in the control group; the difference was
      strongly significant (P<0.001). CONCLUSION: The study shows that anemia, preterm
      delivery, and low birth weight were more prevalent among teenagers than among
      women who were 20-24 years old. This indicates the need for enhancing family
      welfare measures to delay the age at first pregnancy, thereby reducing the
      multiple complications that may occur in the young mother and her newborn baby.

PMID- 20049302
TI  - Assessment of Risk Factors for Development of Type-II Diabetes Mellitus Among
      Working Women in Berhampur, Orissa.
AB  - OBJECTIVES: 1) Assess general health condition and anthropological parameters of
      the working women. 2) Identify prevalence of Type-II Diabetes among them. 3)
      Assess risk factors associated with development of diabetes. 4) Educate them
      about Life Style Modifications. MATERIALS AND METHODS: A cross sectional study
      was carried out in six educational institutes. A total of 100 working women were
      selected as study population. During the two-month study period, Fasting Blood
      Sugar (FBS) was estimated to identify the diabetics and the Impaired Glucose
      Tolerance (IGT). Information from the study population was collected through pre
      tested questionnaire using several anthropometric measurements. RESULTS: Out of
      100 women, 24 were having FBS compatible with IGT or diabetes. The incidence was
      highest in 46 to 55 yr age group. 75% of women with diabetes or IGT were in
      higher income group. Body Mass Index was more than 25 kg/m(2) in maximum (75%)
      women having diabetes or IGT. 92% women with diabetes or IGT had their Waist Hip
      Ratio >/=0.85. Moreover, orientation towards healthy life style modification to
      control diabetes and its prevention was poor among the study population.
      CONCLUSION: Prevalence of diabetes and IGT was higher among urban working women
      and is increasing with increase in age. Obesity plays a major role in development
      of Type 2 diabetes. Several long- and short-term steps should be taken for
      promotion of healthy life style modifications to prevent diabetes and emergence
      of its complications.

PMID- 20049303
TI  - Enteric Pathogens in HIV/AIDS from a Tertiary Care Hospital.
AB  - BACKGROUND: Patterns of enteric infections in HIV in developing countries may
      differ in several important ways from developed countries, the knowledge of which
      can often guide therapy when resource limitations hamper the exact diagnosis of
      the etiological agent in HIV-associated diarrhea. OBJECTIVES: The primary
      objective of this study was to define and compare the microbial etiologies of
      diarrhea in HIV-1 infected and non infected patients and in HIV infected non
      diarrheal patients. MATERIALS AND METHODS: This study was conducted between April
      2007 and July 2007 at the Department of Microbiology, Maulana Azad Medical
      College, New Delhi. Stool samples from 50 HIV seropositive cases with diarrhea
      (study group), 50 HIV seropositive cases without diarrhea (control group I), and
      50 HIV seronegative cases with diarrhea (control group II) were examined. After
      the diagnosis of HIV infection was made, routine parasitological and
      bacteriological detection was done. An ELISA was used for the detection of
      Clostridium difficile toxin and Cryptosporidium antigen in stool samples.
      RESULTS: The overall prevalence of enteric parasitosis in the study group was 20%
      and the bacteria identified were Escherischia coli in 24% of the case,
      Clostridium difficile in 10% of the cases, Salmonella species and Vibrio cholerae
      in 4% of the cases, and Shigella species in 2% of the cases. Candida species was
      identified in 36% of the cases. CONCLUSIONS: Identification of the etiological
      agent of diarrhea in a patient with AIDS is very important as it can help in the
      institution of appropriate therapy and the reduction of morbidity and mortality
      in these patients.

PMID- 20049304
TI  - Breast feeding practices and newborn care in rural areas: a descriptive cross
      sectional study.
AB  - CONTEXT: Breastfeeding practices play an important role in reducing child
      mortality and morbidity. This study was aimed to describe the breastfeeding
      practices prevalent in rural areas. OBJECTIVES: The primary objective of this
      study was to describe the breastfeeding and newborn care practices in rural areas
      and the secondary objective was to describe the factors affecting the initiation
      and duration of breastfeeding. SETTINGS AND DESIGN: The study was conducted in
      primary health care center (PHC) that is attached to a medical college in
      Kengeri, rural Bangalore, Karnataka. MATERIALS AND METHODS: Mothers with children
      who were 9 months old who came to the PHC for measles vaccination were included
      in the study and data was collected using the pre-tested questionnaire on
      breastfeeding and newborn practices. RESULTS: Our study shows 97% of the mothers
      initiated breastfeeding, 19% used pre lacteal feeds, 90% had hospital deliveries
      and 10% had home deliveries, and 50% used a house knife to cut the umbilical cord
      among home deliveries. CONCLUSIONS: This study emphasizes the need for
      breastfeeding intervention programs especially for the mother during antenatal
      and postnatal check-ups and practices like discarding the colostrum and
      early/late weaning are still widely prevalent and need to be addressed.

PMID- 20049305
TI  - The Culture of Bottle-feeding.

PMID- 20049306
TI  - Knowledge and attitudes of anganwadi supervisor workers about infant
      (breastfeeding and complementary) feeding in gondia district.

PMID- 20049307
TI  - Role of Intensive Training in Strengthening the Skills of HIV Counselors for
      Imparting Quality ICTC Services.

PMID- 20049308
TI  - Overweight, obesity and influence of stress on body weight among undergraduate
      medical students.

PMID- 20049309
TI  - Treatment seeking pattern among parents of children with locomotor disablity.

PMID- 20049310
TI  - A Program on Prevention of Mother to Child Transmission of HIV at Government
      Hospital, Tiruchengode Taluk, Namakkal District.

PMID- 20049311
TI  - Prevalence of hepatitis C virus in aligarh: a seven year experience.

PMID- 20049312
TI  - Family planning prevalence among postpartum mothers attending child welfare
      clinics - a sri lankan experience.

PMID- 20049313
TI  - Future of community medicine in India.

PMID- 20049314
TI  - Biased goiter prevalence estimate.

PMID- 20049315
TI  - WHO Indicators for Valid Assessment of Iodine Deficiency Disorders.

PMID- 20049316
TI  - Persistent left superior vena cava and partial anomalous pulmonary venous return
      in an old asymptomatic female patient.
AB  - Persistent left superior vena cava is a rare congenital venous anomaly. It
      results from failure of closure of the left anterior cardinal vein during cardiac
      development. It is usually asymptomatic but can be associated with other
      congenital cardiac defects including atrial septal defects, ventricular septal
      defects, endocardial cushion defects, tetralogy of Fallot and rhythm
      disturbances. PLSVC should be considered in the presence of a dilated coronary
      sinus on transthoracic echocardiography. The diagnosis can be made when injection
      of contrast in left antecubital vein results in enhancement of the dilated
      coronary sinus before right atrium. MRI, CT-scan and catheterisation can be used
      to confirm the diagnosis.

PMID- 20049317
TI  - Medium-Chain Acyl-CoA Dehydrogenase Deficiency in an Infant with Dilated
      Cardiomyopathy.
AB  - We report about an infant affected by dilated cardiomyopathy (CMP) in whom
      metabolic investigations evidenced medium-chain-acyl-CoA dehydrogenase deficiency
      (MCADD), that is one of three types of inherited disorders of mitochondrial fatty
      acid beta-oxidation. Long-chain and very long-chain 3-hydroxyacyl-coenzyme A
      dehydrogenase deficits are recognized as responsible of hypertrophic or, less
      frequently, dilated cardiomyopathy (CMP) in childhood. Otherwise, to our
      knowledge, no case of MCADD associated to dilated CMP has been reported in
      literature.

PMID- 20049318
TI  - Ross-kabbani operation in an infant with mitral valve dysplasia.
AB  - Background. Mitral valve replacement can be very difficult to obtain in infants
      because the valve annulus diameter can be smaller than the available prosthesis.
      Case Report. We describe the case of a 2-month-old female weighing 3.5 kg
      affected by mitral valve dysplasia leading to severe valve stenosis. Despite full
      medication, the clinical conditions were critical and surgery was undertaken. The
      mitral valve was unsuitable for repair and the orifice of mitral anulus was 12
      mm, too small for a mechanical prosthesis. Therefore, a Ross-Kabbani operation
      was undertaken, replacing the mitral valve with the pulmonary autograft and
      reconstructing the right ventricular outflow tract with an etherograft. Results.
      The postoperative course was uneventful and the clinical conditions are good at 4
      month follow-up. Conclusion. The Ross-Kabbani operation can be an interesting
      alternative to mitral valve replacement in infants when valve repair is not
      achievable and there is little space for an intra-annular mechanical prosthesis
      implant.

PMID- 20049319
TI  - Is race a risk factor for the development of renal artery stenosis?
AB  - Atherosclerotic renal artery disease is a common cause of hypertension and
      chronic kidney disease that may progress into end stage renal failure if not
      diagnosed and treated early. Renal artery stenosis (RAS) has been shown to be an
      independent risk factor for mortality in patients with coronary artery disease.
      We sought to determine whether race is an independent risk factor for developing
      RAS. A retrospective study was conducted including 324 patients with resistant
      hypertension who underwent renal angiography with or without coronary
      angiography. In univariate analysis, Caucasian race was associated with
      significant risk of RAS (OR = 2.3, P = .01). However, this association was no
      longer significant after correcting for additional clinical variables in a
      multivariate model (OR = 1.5, P = .07). There was a strong association between
      smoking and RAS (OR 2.0, P = .02). We conclude that traditional risk factors,
      especially smoking, rather than race, are the most important predictors of RAS
      development.

PMID- 20049320
TI  - Diffuse supravalvular aortic stenosis: surgical repair in adulthood.
AB  - We present the case of a 54-year-old woman in which a diffuse congenital
      supravalvular aortic stenosis (SVAS) was associated with a severe aortic valve
      incompetence and heavy calcification of the aortic annulus. Repair consisted in
      resection of the ascending aorta, patch augmentation of the hypoplastic aortic
      root and annulus, placement of a 20 mm Dacron tubular graft (Vascutek,
      Renfrewshire, UK) and aortic valve replacement with a mechanical prosthesis
      (Sorin, Turin, Italy). Follow-up echocardiography demonstrated normal prosthetic
      valve function and a postoperative three-dimensional computed tomographic scan
      showed a normal shape of the reconstructed ascending aorta.

PMID- 20049321
TI  - Differential impact of tumor suppressor pathways on DNA damage response and
      therapy-induced transformation in a mouse primary cell model.
AB  - The RB and p53 tumor suppressors are mediators of DNA damage response, and
      compound inactivation of RB and p53 is a common occurrence in human cancers.
      Surprisingly, their cooperation in DNA damage signaling in relation to
      tumorigenesis and therapeutic response remains enigmatic. In the context of
      individuals with heritable retinoblastoma, there is a predilection for secondary
      tumor development, which has been associated with the use of radiation-therapy to
      treat the primary tumor. Furthermore, while germline mutations of the p53 gene
      are critical drivers for cancer predisposition syndromes, it is postulated that
      extrinsic stresses play a major role in promoting varying tumor spectrums and
      disease severities. In light of these studies, we examined the tumor suppressor
      functions of these proteins when challenged by exposure to therapeutic stress. To
      examine the cooperation of RB and p53 in tumorigenesis, and in response to
      therapy-induced DNA damage, a combination of genetic deletion and dominant
      negative strategies was employed. Results indicate that loss/inactivation of RB
      and p53 is not sufficient for cellular transformation. However, these proteins
      played distinct roles in response to therapy-induced DNA damage and subsequent
      tumorigenesis. Specifically, RB status was critical for cellular response to
      damage and senescence, irrespective of p53 function. Loss of RB resulted in a
      dramatic evolution of gene expression as a result of alterations in epigenetic
      programming. Critically, the observed changes in gene expression have been
      specifically associated with tumorigenesis, and RB-deficient, recurred cells
      displayed oncogenic characteristics, as well as increased resistance to
      subsequent challenge with discrete therapeutic agents. Taken together, these
      findings indicate that tumor suppressor functions of RB and p53 are particularly
      manifest when challenged by cellular stress. In the face of such challenge, RB is
      a critical suppressor of tumorigenesis beyond p53, and RB-deficiency could
      promote significant cellular evolution, ultimately contributing to a more
      aggressive disease.

PMID- 20049322
TI  - Estrogen receptor alpha as a key target of red wine polyphenols action on the
      endothelium.
AB  - BACKGROUND: A greater reduction in cardiovascular risk and vascular protection
      associated with diet rich in polyphenols are generally accepted; however, the
      molecular targets for polyphenols effects remain unknown. Meanwhile evidences in
      the literature have enlightened, not only structural similarities between
      estrogens and polyphenols known as phytoestrogens, but also in their vascular
      effects. We hypothesized that alpha isoform of estrogen receptor (ERalpha) could
      be involved in the transduction of the vascular benefits of polyphenols.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we used ERalpha deficient mice to show that
      endothelium-dependent vasorelaxation induced either by red wine polyphenol
      extract, Provinols, or delphinidin, an anthocyanin that possesses similar
      pharmacological profile, is mediated by ERalpha. Indeed, Provinols, delphinidin
      and ERalpha agonists, 17-beta-estradiol and PPT, are able to induce endothelial
      vasodilatation in aorta from ERalpha Wild-Type but not from Knock-Out mice, by
      activation of nitric oxide (NO) pathway in endothelial cells. Besides, silencing
      the effects of ERalpha completely prevented the effects of Provinols and
      delphinidin to activate NO pathway (Src, ERK 1/2, eNOS, caveolin-1) leading to NO
      production. Furthermore, direct interaction between delphinidin and ERalpha
      activator site is demonstrated using both binding assay and docking. Most
      interestingly, the ability of short term oral administration of Provinols to
      decrease response to serotonin and to enhance sensitivity of the endothelium
      dependent relaxation to acetylcholine, associated with concomitant increased NO
      production and decreased superoxide anions, was completely blunted in ERalpha
      deficient mice. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that red
      wine polyphenols, especially delphinidin, exert their endothelial benefits via
      ERalpha activation. It is a major breakthrough bringing new insights of the
      potential therapeutic of polyphenols against cardiovascular pathologies.

PMID- 20049323
TI  - Loss of Smyhc1 or Hsp90alpha1 function results in different effects on myofibril
      organization in skeletal muscles of zebrafish embryos.
AB  - BACKGROUND: Myofibrillogenesis requires the correct folding and assembly of
      sarcomeric proteins into highly organized sarcomeres. Heat shock protein 90alpha1
      (Hsp90alpha1) has been implicated as a myosin chaperone that plays a key role in
      myofibrillogenesis. Knockdown or mutation of hsp90alpha1 resulted in complete
      disorganization of thick and thin filaments and M- and Z-line structures. It is
      not clear whether the disorganization of these sarcomeric structures is due to a
      direct effect from loss of Hsp90alpha1 function or indirectly through the
      disorganization of myosin thick filaments. METHODOLOGY/PRINCIPAL FINDINGS: In
      this study, we carried out a loss-of-function analysis of myosin thick filaments
      via gene-specific knockdown or using a myosin ATPase inhibitor BTS (N-benzyl-p
      toluene sulphonamide) in zebrafish embryos. We demonstrated that knockdown of
      myosin heavy chain 1 (myhc1) resulted in sarcomeric defects in the thick and thin
      filaments and defective alignment of Z-lines. Similarly, treating zebrafish
      embryos with BTS disrupted thick and thin filament organization, with little
      effect on the M- and Z-lines. In contrast, loss of Hsp90alpha1 function
      completely disrupted all sarcomeric structures including both thick and thin
      filaments as well as the M- and Z-lines. CONCLUSION/SIGNIFICANCE: Together, these
      studies indicate that the hsp90alpha1 mutant phenotype is not simply due to
      disruption of myosin folding and assembly, suggesting that Hsp90alpha1 may play a
      role in the assembly and organization of other sarcomeric structures.

PMID- 20049324
TI  - Accuracy and reliability of pallor for detecting anaemia: a hospital-based
      diagnostic accuracy study.
AB  - BACKGROUND: Anaemia is a common disorder. Most health providers in resource poor
      settings rely on physical signs to diagnose anaemia. We aimed to determine the
      diagnostic accuracy of pallor for anaemia by using haemoglobin as the reference
      standard. METHODOLOGY/PRINCIPAL FINDINGS: In May 2007, we enrolled consecutive
      patients over 12 years of age, able to consent and willing to participate and who
      had a haemoglobin measurement taken within a day of assessment of clinical pallor
      from outpatient and medicine inpatient department of a teaching hospital. We did
      a blind and independent comparison of physical signs (examination of
      conjunctivae, tongue, palms and nailbed for pallor) and the reference standard
      (haemoglobin estimation by an electronic cell counter). Diagnostic accuracy was
      measured by calculating likelihood ratio values and 95% confidence intervals (CI)
      at different haemoglobin thresholds and area under the receiver operating
      characteristic curve. Two observers examined a subset of patients (n = 128) to
      determine the inter-observer agreement, calculated by kappa statistics. We
      studied 390 patients (mean age 40.1 [SD 17.08] years); of whom 48% were women.
      The haemoglobin was <7 g/dL in 8% (95% confidence interval, 5, 10) patients; <9
      g/dL in 21% (17, 26) patients and <12 g/dL in 64% (60, 70) patients. Among
      patients with haemoglobin <7 g/dL, presence of severe tongue pallor yielded a LR
      of 9.87 (2.81, 34.6) and its absence yielded a LR of 0. The tongue pallor
      outperformed other pallor sites and was also the best discriminator of anaemia at
      haemoglobin thresholds of 7 g/dL and 9 g/dL (area under the receiver operating
      characteristic curves (ROC area = 0.84 [0.77, 0.90] and 0.71[0.64, 0.76])
      respectively. The agreement between the two observers for detection of anaemia
      was poor (kappa values = 0.07 for conjunctival pallor and 0.20 for tongue
      pallor). CONCLUSIONS/SIGNIFICANCE: Clinical assessment of pallor can rule out and
      modestly rule in severe anaemia.

PMID- 20049326
TI  - Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii
      infection in a mouse model.
AB  - Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in
      a susceptible host years or decades after the primary infection; however, the
      mechanisms of reactivation and the cellular reservoir during latency are poorly
      understood. Herein we describe a murine model for Brill-Zinsser disease, and use
      PCR and cell culture to show transient rickettsemia in mice treated with
      dexamethasone >3 months after clinical recovery from the primary infection.
      Treatment of similarly infected mice with cyclosporine failed to produce
      recrudescent bacteremia. Therapy with doxycycline for the primary infection
      prevented recrudescent bacteremia in most of these mice following treatment with
      dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was
      detected by PCR, cell culture, and immunostaining methods in murine adipose
      tissue, but not in liver, spleen, lung, or central nervous system tissues of mice
      4 months after recovery from the primary infection. The lungs of dexamethasone
      treated mice showed impaired expression of beta-defensin transcripts that may be
      involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii
      rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1.
      Collectively these data suggest a role for adipose tissue as a potential
      reservoir for dormant infections with R. prowazekii.

PMID- 20049325
TI  - Human prion diseases in the United States.
AB  - BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative
      disorders that affect humans and animals. The most common form of human prion
      disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a
      recently emerged human prion disease, is a zoonotic foodborne disorder that
      occurs almost exclusively in countries with outbreaks of bovine spongiform
      encephalopathy. This study describes the occurrence and epidemiology of CJD and
      vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and
      vCJD deaths using death certificates of US residents for 1979-2006, and those
      identified through other surveillance mechanisms during 1996-2008. Since CJD is
      invariably fatal and illness duration is usually less than one year, the CJD
      incidence is estimated as the death rate. During 1979 through 2006, an estimated
      6,917 deaths with CJD as a cause of death were reported in the United States, an
      annual average of approximately 247 deaths (range 172-304 deaths). The average
      annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most
      (61.8%) of the CJD deaths occurred among persons >or=65 years of age for an
      average annual incidence of 4.8 per 1,000,000 persons in this population. Most
      deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7
      times higher than that for blacks (1.04 and 0.40, respectively). Three patients
      who died since 2004 were reported with vCJD; epidemiologic evidence indicated
      that their infection was acquired outside of the United States.
      CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence
      rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by
      age and race in the United States. Ongoing surveillance remains important for
      monitoring the stability of the CJD incidence rates, and detecting occurrences of
      vCJD and possibly other novel prion diseases in the United States.

PMID- 20049327
TI  - Automated discovery of novel drug formulations using predictive iterated high
      throughput experimentation.
AB  - BACKGROUND: We consider the problem of optimizing a liposomal drug formulation: a
      complex chemical system with many components (e.g., elements of a lipid library)
      that interact nonlinearly and synergistically in ways that cannot be predicted
      from first principles. METHODOLOGY/PRINCIPAL FINDINGS: The optimization criterion
      in our experiments was the percent encapsulation of a target drug, Amphotericin
      B, detected experimentally via spectrophotometric assay. Optimization of such a
      complex system requires strategies that efficiently discover solutions in
      extremely large volumes of potential experimental space. We have designed and
      implemented a new strategy of evolutionary design of experiments (Evo-DoE), that
      efficiently explores high-dimensional spaces by coupling the power of computer
      and statistical modeling with experimentally measured responses in an iterative
      loop. CONCLUSIONS: We demonstrate how iterative looping of modeling and
      experimentation can quickly produce new discoveries with significantly better
      experimental response, and how such looping can discover the chemical landscape
      underlying complex chemical systems.

PMID- 20049328
TI  - Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated
      phosphorylation.
AB  - BACKGROUND: Circadian rhythms govern a large array of physiological and metabolic
      functions. To achieve plasticity in circadian regulation, proteins constituting
      the molecular clock machinery undergo various post-translational modifications
      (PTMs), which influence their activity and intracellular localization. The core
      clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3beta
      signaling pathway regulates BMAL1 protein stability and activity. PRINCIPAL
      FINDINGS: GSK3beta phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and
      primes it for ubiquitylation. In the absence of GSK3beta-mediated
      phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene
      expression is dampened. Dopamine D2 receptor mediated signaling, known to control
      the Akt-GSK3beta pathway, influences BMAL1 stability and in vivo circadian gene
      expression in striatal neurons. CONCLUSIONS: These findings uncover a previously
      unknown mechanism of circadian clock control. The GSK3beta kinase phosphorylates
      BMAL1, an event that controls the stability of the protein and the amplitude of
      circadian oscillation. BMAL1 phosphorylation appears to be an important
      regulatory step in maintaining the robustness of the circadian clock.

PMID- 20049330
TI  - Askin's Tumor in an Adult: Case Report and Findings on 18F-FDG PET/CT.
AB  - Primitive neuroectodermal tumor (PNET) of the chest wall or Askin's tumor is a
      rare neoplasm of chest wall. It most often affects children and adolescents and
      is a very rare tumor in adults. In this case report, we present an Askin's tumor
      occurred in a 73-year-old male. The patient was admitted with a history of 3
      month lower back pain and cough. In computed tomography, there was a lesion with
      dimensions of 70 x 40 x 65 mm in the superior segment of the lower lobe of the
      left lung. Positron emission tomography/computed tomography with 18F
      flourodeoxyglucose revealed a pleural-based tumor in the left lung with a maximum
      standardized uptake value of 4.36. No distant or lymph node metastases were
      present. The patient had gone through surgery, and wedge resection of the
      superior segment of left lobe and partial resection of the ipsilateral ribs were
      performed. Pathology report with immunocytochemistry was consistent with PNET and
      the patient received chemotherapy after that.

PMID- 20049329
TI  - Hypoglycemia and the origin of hypoxia-induced reduction in human fetal growth.
AB  - BACKGROUND: The most well known reproductive consequence of residence at high
      altitude (HA >2700 m) is reduction in fetal growth. Reduced fetoplacental
      oxygenation is an underlying cause of pregnancy pathologies, including
      intrauterine growth restriction and preeclampsia, which are more common at HA.
      Therefore, altitude is a natural experimental model to study the etiology of
      pregnancy pathophysiologies. We have shown that the proximate cause of decreased
      fetal growth is not reduced oxygen availability, delivery, or consumption. We
      therefore asked whether glucose, the primary substrate for fetal growth, might be
      decreased and/or whether altered fetoplacental glucose metabolism might account
      for reduced fetal growth at HA. METHODS: Doppler and ultrasound were used to
      measure maternal uterine and fetal umbilical blood flows in 69 and 58 residents
      of 400 vs 3600 m. Arterial and venous blood samples from mother and fetus were
      collected at elective cesarean delivery and analyzed for glucose, lactate and
      insulin. Maternal delivery and fetal uptakes for oxygen and glucose were
      calculated. PRINCIPAL FINDINGS: The maternal arterial - venous glucose
      concentration difference was greater at HA. However, umbilical venous and
      arterial glucose concentrations were markedly decreased, resulting in lower
      glucose delivery at 3600 m. Fetal glucose consumption was reduced by >28%, but
      strongly correlated with glucose delivery, highlighting the relevance of glucose
      concentration to fetal uptake. At altitude, fetal lactate levels were increased,
      insulin concentrations decreased, and the expression of GLUT1 glucose transporter
      protein in the placental basal membrane was reduced. CONCLUSION/SIGNIFICANCE: Our
      results support that preferential anaerobic consumption of glucose by the
      placenta at high altitude spares oxygen for fetal use, but limits glucose
      availability for fetal growth. Thus reduced fetal growth at high altitude is
      associated with fetal hypoglycemia, hypoinsulinemia and a trend towards
      lactacidemia. Our data support that placentally-mediated reduction in glucose
      transport is an initiating factor for reduced fetal growth under conditions of
      chronic hypoxemia.

PMID- 20049331
TI  - LDLR expression and localization are altered in mouse and human cell culture
      models of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and
      the most common form of dementia. The major molecular risk factor for late-onset
      AD is expression of the epsilon-4 allele of apolipoprotein E (apoE), the major
      cholesterol transporter in the brain. The low-density lipoprotein receptor (LDLR)
      has the highest affinity for apoE and plays an important role in brain
      cholesterol metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Using RT-PCR and western
      blotting techniques we found that over-expression of APP caused increases in both
      LDLR mRNA and protein levels in APP transfected H4 neuroglioma cells compared to
      H4 controls. Furthermore, immunohistochemical experiments showed aberrant
      localization of LDLR in H4-APP neuroglioma cells, Abeta-treated primary neurons,
      and in the PSAPP transgenic mouse model of AD. Finally, immunofluorescent
      staining of LDLR and of gamma- and alpha-tubulin showed a change in LDLR
      localization preferentially away from the plasma membrane that was paralleled by
      and likely the result of a disruption of the microtubule-organizing center and
      associated microtubule network. CONCLUSIONS/SIGNIFICANCE: These data suggest that
      increased APP expression and Abeta exposure alters microtubule function, leading
      to reduced transport of LDLR to the plasma membrane. Consequent deleterious
      effects on apoE uptake and function will have implications for AD pathogenesis
      and/or progression.

PMID- 20049333
TI  - Aortocaval Fistula in a Behcet's Disease Patient.
AB  - Behcet's disease (BD) is a chronic, recurrent, systemic disease that is
      characterized by oral and genital ulcers and oculocutaneous inflammatory lesions.
      Cardiovascular involvement especially large artery involvement is a serious and
      vital complication of BD. Pseudoaneurysms in the major arteries may be the cause
      of sudden death in BD. In our case a pulsatile abdominal mass was determined to
      be an aortic pseudoaneurysm associated with BD and an aortocaval fistula. Here we
      report this case and a short review of literature because this is the first
      reported aortocaval fistula in a BD patient in English literature.

PMID- 20049332
TI  - Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus
      hemagglutinin.
AB  - The pandemic influenza virus (2009 H1N1) was recently introduced into the human
      population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from "classical
      swine H1N1" virus, which likely shares a common ancestor with the human H1N1
      virus that caused the pandemic in 1918, whose descendant viruses are still
      circulating in the human population with highly altered antigenicity of HA.
      However, information on the structural basis to compare the HA antigenicity among
      2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking.
      By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and
      the 1918 pandemic virus share a significant number of amino acid residues in
      known antigenic sites, suggesting the existence of common epitopes for
      neutralizing antibodies cross-reactive to both HAs. It was noted that the early
      human H1N1 viruses isolated in the 1930s-1940s still harbored some of the
      original epitopes that are also found in 2009 H1N1. Interestingly, while 2009
      H1N1 HA lacks the multiple N-glycosylations that have been found to be associated
      with an antigenic change of the human H1N1 virus during the early epidemic of
      this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which
      became N-glycosylation sites via a single nucleotide mutation in the human H1N1
      virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the
      conserved amino acids will soon be targeted by antibody-mediated selection
      pressure in humans. Indeed, amino acid substitutions predicted here are occurring
      in the recent 2009 H1N1 variants. The present study suggests that antibodies
      elicited by natural infection with the 1918 pandemic or its early descendant
      viruses play a role in specific immunity against 2009 H1N1, and provides an
      insight into future likely antigenic changes in the evolutionary process of 2009
      H1N1 in the human population.

PMID- 20049335
TI  - Intussusception in a premature neonate: a rare often misdiagnosed cause of
      intestinal obstruction.
AB  - Intestinal obstruction in neonatal period is an emergency caused by many surgical
      causes. An extremely rare surgical cause in this group of age is intussusception
      which can be easily confused with other surgical entities. In several reports, a
      significant number of the infants who were included in the study population were
      believed to have necrotizing enterocolitis (NEC). We present a rare cause of
      small intestine obstruction in a preterm female infant that can be easily
      misdiagnosed and confused preoperatively with other clinical entities particular
      for this period.

PMID- 20049334
TI  - Sleep deprivation influences diurnal variation of human time perception with
      prefrontal activity change: a functional near-infrared spectroscopy study.
AB  - Human short-time perception shows diurnal variation. In general, short-time
      perception fluctuates in parallel with circadian clock parameters, while diurnal
      variation seems to be modulated by sleep deprivation per se. Functional imaging
      studies have reported that short-time perception recruits a neural network that
      includes subcortical structures, as well as cortical areas involving the
      prefrontal cortex (PFC). It has also been reported that the PFC is vulnerable to
      sleep deprivation, which has an influence on various cognitive functions. The
      present study is aimed at elucidating the influence of PFC vulnerability to sleep
      deprivation on short-time perception, using the optical imaging technique of
      functional near-infrared spectroscopy. Eighteen participants performed 10-s time
      production tasks before (at 21:00) and after (at 09:00) experimental nights both
      in sleep-controlled and sleep-deprived conditions in a 4-day laboratory-based
      crossover study. Compared to the sleep-controlled condition, one-night sleep
      deprivation induced a significant reduction in the produced time simultaneous
      with an increased hemodynamic response in the left PFC at 09:00. These results
      suggest that activation of the left PFC, which possibly reflects functional
      compensation under a sleep-deprived condition, is associated with alteration of
      short-time perception.

PMID- 20049336
TI  - A novel platelet activating factor receptor antagonist reduces cell infiltration
      and expression of inflammatory mediators in mice exposed to desiccating
      conditions after PRK.
AB  - PURPOSE: To study the contribution of a novel PAF receptor antagonist LAU-0901 in
      the modulation of the increased inflammatory response in mice exposed to
      dessicating conditions (DE) after PRK. METHODS: Eighty 13-14 week old female
      Balb/C mice were used. They were divided into two groups: One group was treated
      with LAU-0901 topical drops. The other group was treated with vehicle. In each
      group ten mice served as controls and ten were placed in DE. The other twenty
      mice underwent bilateral PRK and were divided in two additional groups: ten mice
      remained under normal conditions (NC) and the other ten were exposed to DE. After
      1 week all animals underwent in vivo confocal microscopy, immunostaining and
      western blotting analysis. RESULTS: Confocal microscopy showed an increased
      number of reflective structures in the corneal epithelium after PRK and exposure
      to DE in eyes treated with vehicle as compared to eyes treated with LAU-090).
      Significant decrease of COX-2 and Arginase I expression and reduced alpha SMA
      cells was observed after PRK and exposure to DE in eyes treated with LAU-0901.
      DISCUSSION: Exposure of mice to a DE after PRK increases the epithelial turnover
      rate. PAF is involved in the inflammatory cell infiltration and expression of
      inflammatory cytokines that follow PRK under DE.

PMID- 20049337
TI  - Laparoscopic distal pancreatectomy with splenic conservation: an operation
      without increased morbidity.
AB  - OBJECTIVES: The advent of minimally invasive techniques was marked by a paradigm
      shift towards the use of laparoscopy for benign distal pancreatic masses. Herein
      we describe one center's experience with laparoscopic distal pancreatectomy.
      METHODS: A retrospective chart review was performed for all distal
      pancreatectomies completed laparoscopically from 1999 to 2009. Outcomes from
      those cases completed with a concurrent splenectomy were compared to the spleen
      preserving procedures. RESULTS: Twenty-four patients underwent laparoscopic
      distal pancreatectomy. Seven had spleen-conserving operations. There was no
      difference in the mean estimated blood loss (316 versus 285 mL, P = .5) or
      operative time (179 versus 170 minutes, P = .9). The mean tumor size was not
      significantly different (3.1 versus 2.2 cm, P = .9). There was no difference in
      the average hospital stay (7.1 versus 7.0 days, P = .7). Complications in the
      spleen-preserving group included one iatrogenic colon injury, two pancreatic
      fistulas, and two cases of iatrogenic diabetes. In the splenectomy group, two
      developed respiratory failure, three acquired iatrogenic diabetes, and two
      suffered pancreatic fistulas (71% versus 41%, P = .4). CONCLUSIONS: The
      laparoscopic distal pancreatectomy is a safe operation with a low morbidity.
      Splenic conservation does not significantly increase the morbidity of the
      procedure.

PMID- 20049338
TI  - Quantitative estimation of the nonstationary behavior of neural spontaneous
      activity.
AB  - The "stationarity time" (ST) of neuronal spontaneous activity signals of rat
      embryonic cortical cells, measured by means of a planar Multielectrode Array
      (MEA), was estimated based on the "Detrended Fluctuation Analysis" (DFA). The ST
      is defined as the mean time interval during which the signal under analysis keeps
      its statistical characteristics constant. An upgrade on the DFA method is
      proposed, leading to a more accurate procedure. Strong statistical correlation
      between the ST, estimated from the Absolute Amplitude of Neural Spontaneous
      Activity (AANSA) signals and the Mean Interburst Interval (MIB), calculated by
      classical spike sorting methods applied to the interspike interval time series,
      was obtained. In consequence, the MIB may be estimated by means of the ST, which
      further includes relevant biological information arising from basal activity. The
      results point out that the average ST of MEA signals lies between 2-3 seconds.
      Furthermore, it was shown that a neural culture presents signals that lead to
      different statistical behaviors, depending on the relative geometric position of
      each electrode and the cells. Such behaviors may disclose physiological
      phenomena, which are possibly associated with different adaptation/facilitation
      mechanisms.

PMID- 20049339
TI  - A Unifying Theory for SIDS.
AB  - The Sudden Infant Death Syndrome (SIDS) has four distinctive characteristics that
      must be explained by any theory proposed for it. (1) A characteristic male
      fraction of approximately 0.61 for all postneonatal SIDS in the US; (2) a
      distinctive lognormal-type age distribution arising from zero at birth, mode at
      about 2 months, median at about 3 months, and an exponential decrease with age
      going towards zero beyond one year; (3) a marked decrease in SIDS rate from the
      discovery that changing the recommended infant sleep position from prone to
      supine reduced the rate of SIDS, but it did not change the form of the age or
      gender distributions cited above; (4) a seasonal variation, maximal in winter and
      minimal in summer, that implies subsets of SIDS displaying evidence of seasonal
      low-grade respiratory infection and nonseasonal neurological prematurity. A
      quadruple-risk model is presented that fits these conditions but requires
      confirmatory testing by finding a dominant X-linked allele protective against
      cerebral anoxia that is missing in SIDS.

PMID- 20049340
TI  - Detection of autoantibodies against recombinant desmoglein 1 and 3 molecules in
      patients with pemphigus vulgaris: correlation with disease extent at the time of
      diagnosis and during follow-up.
AB  - The recent availability of cDNA clones for pemphigus antigens has allowed the
      production of recombinant desmoglein 1 and desmoglein 3 molecules and the
      development of an ELISA approach in order to determine levels of antibodies to
      them. The aim of the study was to determine the relationship between
      autoantibodies levels and the extent of both mucosal and skin lesions in 20
      patients with pemphigus vulgaris at the time of diagnosis and during follow-up.
      For the detection of autoantibodies by ELISA we used the recombinant proteins
      expressing overlapping sequences with the entire extracellular desmoglein 1 and
      desmoglein 3 domains. We showed that in presence of mucosal lesions there was a
      correlation between extension of mucosal involvement and autoantibodies titres
      against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions
      there was a statistically significant correlation between extension of skin
      lesions and autoantibodies titres against desmoglein 3, but not against
      desmoglein 1. A not negligible number of patients showed variations of the
      desmoglein 3 autoantibodies titre which did not correlate with the severity of
      both cutaneous and mucosal involvement. Similar results were obtained analyzing
      autoantibodies titres against desmoglein 1. In conclusion, we believe that the
      utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should
      be used with caution to monitor disease severity and response to therapy,
      although it remains a high specific test for the initial diagnosis of pemphigus
      and the identification of a change in the clinical phenotype of this condition.

PMID- 20049341
TI  - Meta-analytic structural equation modeling of the influences of family-centered
      care on parent and child psychological health.
AB  - Background. Family-centered care is now practiced throughout the world by
      physicians, nurses, and allied health care professionals. The call for adoption
      of family-centered care is based on the contention that the physical and
      psychological health of a child is influenced by parents' psychological health
      where family-centered care enhances parent well-being which in turn influences
      child well-being. We empirically assessed whether these relationships are
      supported by available evidence. Method. Meta-analytic structural equation
      modeling was used to test the direct and indirect influences of family-centered
      care and self-efficacy beliefs on parent and child psychological health. Data
      from more than 2900 parents and other caregivers in 15 studies were used for the
      analyses. Results. Family-centered care had indirect effects on parent and child
      psychological health mediated by self-efficacy beliefs. Conclusion. The
      relationships posited in the literature about family-centered care were supported
      by the study results.

PMID- 20049342
TI  - Nosocomial Infections among Pediatric Patients with Neoplastic Diseases.
AB  - Background. Pediatric patients with neoplastic diseases are more likely to
      develop nosocomial infections (NIs). NIs may prolong their hospital stay, and
      increase morbidity and mortality. Objectives. The objectives of this study were
      to determine: (1) the incidence of NIs, (2) sites of NIs, (3) causal organisms,
      and (4) outcomes of NIs among pediatric patients with neoplastic diseases.
      Methods. This study was a prospective cohort study of pediatric patients with
      neoplastic diseases who were admitted to the Chiang Mai University Hospital,
      Thailand. Results. A total of 707 pediatric patients with neoplastic diseases
      were admitted. Forty-six episodes of NIs in 30 patients were reported (6.5
      NIs/100 admission episodes and 7 NIs/1000 days of hospitalization). Patients with
      acute lymphoblastic leukemia had the highest number of NIs (41.3%). The most
      common causal organisms were gram-negative bacteria (47.1%). Patients who had
      undergone invasive procedures were more likely to develop NIs than those who had
      not (P < .05). The mortality rate of patients with NIs was 19.6%. Conclusion.
      Pediatric patients with neoplastic diseases are more likely to develop NIs after
      having undergone invasive procedures. Pediatricians should be aware of this and
      strictly follow infection control guidelines in order to reduce morbidity and
      mortality rates related to NIs.

PMID- 20049343
TI  - Development of items designed to evaluate activity performance and participation
      in children and adolescents with spinal cord injury.
AB  - Background/Objective. Outcomes-based data, whether used clinically or for
      research, are difficult to collect in the pediatric spinal cord injury (SCI)
      population due to a lack of appropriate assessment measures. The purpose of this
      paper is twofold: to describe the process by which two item pools were developed
      to evaluate activity performance and participation among children with SCI and to
      introduce the resultant items specific to pediatric SCI. Methods. The process of
      item development, including construct development, review of related assessment
      tools, chart review, item writing and refinement using focus groups, cognitive
      interviews, and further refinement, was used to create the items pools for
      activity and participation for children and adolescents with SCI. Results. A
      total of 347 items were written for the activity performance construct and 61
      items were written for the participation construct. Several domains were
      established within each construct and items were written for both child and
      parent respondents. Conclusion. The process of detailed item development is the
      first step in the process of developing an outcomes instrument for children and
      adolescents with SCI to assess activity performance and participation. The items
      are representative of pediatric SCI because they address areas specific to
      children and adolescents with SCI such as wheeled mobility, upper extremity
      function with adaptive equipment, role performance, and socialization. After
      testing these items in calibration studies, we will determine if these items can
      be developed into effective computer-adaptive testing applications.

PMID- 20049344
TI  - Logistic Regression and Linear Discriminant Analyses in Evaluating Factors
      Associated with Asthma Prevalence among 10- to 12-Years-Old Children: Divergence
      and Similarity of the Two Statistical Methods.
AB  - Logistic regression and discriminant analyses are both applied in order to
      predict the probability of a specific categorical outcome based upon several
      explanatory variables (predictors). The aim of this work is to evaluate the
      convergence of these two methods when they are applied in data from the health
      sciences. For this purpose, we modeled the association of several factors with
      the prevalence of asthma symptoms with both the two methods and compared the
      result. In conclusion, logistic and discriminant analyses resulted in similar
      models.

PMID- 20049345
TI  - The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian
      Cancer.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is an important novel target in cancer
      therapy. This enzyme is essential in the repair of single-stranded breaks in DNA
      via the base excision repair pathway. Drugs which inhibit PARP are emerging as a
      promising new class of anticancer agents particularly effective against tumors
      which have lost homologous recombination (HR) through loss of functional BRCA1
      and BRCA2. PARP inhibitors potentially represent a major breakthrough for
      patients with hereditary BRCA-associated cancers. Furthermore their role in
      sporadic epithelial ovarian cancer is emerging with identification of additional
      subpopulations of women who may benefit a priority. This paper will summarize the
      mechanism of action of PARP inhibition and its role in the treatment of BRCA1-
      and 2-associated cancers. We will then expand on the broader relevance and future
      directions for PARP inhibition in the clinical setting.

PMID- 20049347
TI  - Funding source and clinical trial outcome.

PMID- 20049348
TI  - Health care reform--let the right voices be heard.

PMID- 20049349
TI  - Acetabular component revision in total hip arthroplasty. Part II: management of
      major bone loss and pelvic discontinuity.
AB  - Use of structural bone graft and/or reconstruction cage devices in acetabular
      revisions with major bone loss has the advantages of providing a stable construct
      at the anatomical hip center of rotation and, theoretically, reconstituting bone
      stock. When the structural graft supports more than 50% of the acetabular
      component, a reconstruction cage device spanning ilium to ischium should be used
      to protect the graft and provide structural stability. Recent introduction of
      trabecular metal cups and augments and custom triflanged acetabular components
      has increased the potential for biological fixation and long-term stability of
      revision constructs. Longer follow-up of these reconstructions is needed.
      Revisions with pelvic discontinuity and major bone loss have a high failure rate
      and require techniques either to reduce and plate the discontinuity or to
      distract the discontinuity to achieve long-term stability.

PMID- 20049350
TI  - Wound management for severe open fractures: use of antibiotic bead pouches and
      vacuum-assisted closure.
AB  - Open fractures complicated by infection, or those requiring extensive soft-tissue
      procedures, are disabling problems for patients and result in significant costs
      for the health care system. As an adjuvant to current protocols involving open
      fractures, antibiotic bead pouches (ABPs) provide high concentrations of local
      antibiotics and can help reduce infection rates. Vacuum-assisted closure (VAC)
      has been shown to decrease the need for, and enhance the success of, free-flap
      coverage for traumatic wounds that are significant enough to preclude primary
      closure, delayed primary closure, or healing by secondary intention. These 2
      modalities may help decrease the complications and costs involved in the
      management of severe open fractures. In this article, we review the theory,
      technique, and efficacy of ABPs and VAC in the management of severe open
      fractures.

PMID- 20049351
TI  - Atrophic nonunion of humeral diaphysis treated with locking plate and recombinant
      bone morphogenetic protein: nine cases.
AB  - Nonunions of the humerus are debilitating for patients and challenging for
      surgeons. We retrospectively reviewed our first 9 humeral nonunions treated with
      a locking plate and commercially available recombinant bone morphogenetic
      protein. At latest follow-up, 8 patients showed clinical and radiographic signs
      of union. One patient had a persistent (11-year) nonunion that failed to unite at
      1 year, despite new bone formation, and underwent revision with the same
      technique. The reported technique is a useful part of the surgeon's armamentarium
      in treating difficult humeral nonunions. We found a high union rate with an
      acceptably low complication rate in this difficult population.

PMID- 20049352
TI  - Porcine small intestine submucosa xenograft augmentation in repair of massive
      rotator cuff tears.
AB  - In this prospective study, we evaluated the efficacy of using porcine small
      intestine submucosa (SIS) xenograft to augment the repair of massive rotator cuff
      tears. Our hypothesis was that SIS xenograft would help restore tendon tissue in
      the human model, as has been shown in several animal studies. Eleven patients
      were followed clinically for a mean of 26 months (range, 14-38 months). Mean
      University of California Los Angeles end-result scores improved from 13.9 before
      surgery to 25.7 after surgery, American Shoulder and Elbow Surgeons scores
      improved from 36.3 to 71.8, and the visual analog scale pain score decreased from
      6.6 to 2.0. All findings were statistically significant (P<.01). At a mean of 25
      months after surgery, magnetic resonance arthrography (MRA) showed the repairs
      partially or completely intact in 44% of shoulders. Intact repairs were thin and
      wispy. There were 3 complications, which included 1 infection and 2 localized
      skin reactions that resolved spontaneously. SIS xenograft did not reconstitute
      rotator cuff tissue or add to the quality of the rotator cuff repair. Given
      clinical concerns about localized reactions in this series and suboptimal MRA
      findings, use of SIS xenograft to augment rotator cuff repairs is not
      recommended.

PMID- 20049353
TI  - Effects of recombinant human bone morphogenetic protein 2 on surgical infections
      in a rabbit posterolateral lumbar fusion model.
AB  - Recombinant human bone morphogenetic proteins (rhBMPs) are often used during
      spine surgery, but their effects on postoperative infections have not been well
      elucidated. Long-bone studies suggest that BMPs may limit local infection and
      facilitate bone formation. Until now, rhBMP-2 had not been evaluated in the
      setting of infected spinal arthrodesis. In the study reported here, we evaluated
      the safety and efficacy of rhBMP-2 and autograft in inducing fusion in the
      setting of surgically acquired infection. Sixty rabbits underwent fusion with
      autograft or rhBMP-2 with coadministration of Staphylococcus aureus or sterile
      saline. In the noninoculated groups, 4/15 autograft and 13/13 rhBMP-2 rabbits
      fused (P<.001). In the inoculated groups, 0/14 autograft and 3/12 rhBMP-2 rabbits
      fused (P = .085). There were 4/14 early deaths caused by infection in the
      autograft group and 0/12 in the rhBMP-2 group (P = .1). Although the difference
      in fusion rates and early deaths from infection for rhBMP-2 and autograft did not
      reach our predetermined alpha error threshold, the data were trending toward
      significance. Our results demonstrated no increase in morbidity or mortality
      associated with use of rhBMP-2 in the setting of local infection. Although BMP
      use with infections remains controversial, these results indicate that rhBMP- 2
      could be used in a contaminated environment.

PMID- 20049355
TI  - Closed-reduction percutaneous pinning of a complex divergent carpometacarpal
      fracture-dislocation involving the 4 ulnar carpometacarpal joints.

PMID- 20049356
TI  - Obturator internus strain in the hip of an adolescent athlete.
AB  - A male 13-year-old presented with acute onset of right hip pain as he prepared to
      kick a soccer ball. A case of acute strain of the obturator internus is reported.
      The strain resolved completely after a period of activity modification and
      physical therapy.

PMID- 20049357
TI  - Intraosseous and extraosseous attachments of flexor tendon to bone: a
      biomechanical in vivo study in rabbits.
AB  - There are 2 popular methods of repairing flexor tendons to the distal phalanx and
      attaching a free tendon graft to bone: intraosseous, by implanting the tendon
      into a bony tunnel, and extraosseous, by suturing the tendon to the cortical
      surface after elevating the periosteum. An in vivo study was designed to
      determine whether one method is stronger than the other. The profundus flexor of
      the third and fourth toes of the hind paw of adult rabbits was divided and
      reattached to the middle phalanx using either an intraosseous tunnel or an
      extraosseous suture. Half the rabbits were killed after 3 weeks, the other half
      after 8 weeks. Repairs were then tested to failure, using an Instron device, and
      compared with the same tendons in the nonoperated limbs. The repaired tendons
      demonstrated similar strength 3 weeks and 8 weeks after surgery but were
      significantly weaker than the nonoperated tendons. The importance of this study
      is that it gives equal credence to these usual methods of tendon attachment.

PMID- 20049358
TI  - Concomitant fractures of capitellum and radial neck in an adolescent.

PMID- 20049359
TI  - Calf endometriosis: a case report and review of musculoskeletal involvement.

PMID- 20049364
TI  - [Uniform format for disclosure of competing interests in ICJME journals].

PMID- 20049365
TI  - Behavioural therapy in the treatment of obesity (I): new directions for clinical
      practice.
AB  - OBJECTIVES: Behavioural therapy (BT) in obesity treatment helps individuals to
      develop skills to achieve healthier body weights. Instead of helping to decide
      what to change, it helps to identify how to change; lifestyle modification is
      essential for any treatment of obesity, be it dieting, medication, surgery, etc.
      Physicians often tend to be unwilling to use BT considering it time-consuming and
      skill-intensive. However, BT can be standardized and used more readily in
      clinical practice. Besides, new approaches have been developed which contribute
      to increase the success of the treatments, like non face-to-face techniques, or
      the new cognitive therapy. SETTING: Classical knowledge on BT has been updated
      with recent publications and information on these new approaches, combined with
      our own experience in the clinical treatment of obesity. RESULTS: Most research
      on BT has been conducted in university-based programs which, despite their
      importance, tell us little about its effectiveness in actual clinical practice.
      Future research might focus on determining how BT can be best applied in a real
      world setting. Examples of new directions are increased maintenance periods, use
      of Internet, and new cognitive therapy. Besides, elucidating the genetic
      component in the prognosis of weight management -the nutrigenomic approach- could
      assist in the development of more effective and individually tailored therapeutic
      strategies; indeed, single nucleotide polymorphisms in candidate genes have been
      related with eating patterns. CONCLUSIONS: This review gives a renewed
      perspective of BT for obesity, offers key-pointers and describes specific ways in
      which medical professionals can promote and encourage self-care of patients.

PMID- 20049366
TI  - Iron deficiency and anaemia in bariatric surgical patients: causes, diagnosis and
      proper management.
AB  - Obesity-induced chronic inflammation leads to activation of the immune system
      that causes alterations of iron homeostasis including hypoferraemia, iron
      restricted erythropoiesis, and finally mild-to-moderate anaemia. Thus,
      preoperative anaemia and iron deficiency are common among obese patients
      scheduled for bariatric surgery (BS). Assessment of patients should include a
      complete haematological and biochemical laboratory work-up, including measurement
      of iron stores, vitamin B12 and folate. In addition, gastrointestinal evaluation
      is recommended for most patients with iron-deficiency anaemia. On the other hand,
      BS is a long-lasting inflammatory stimulus in itself and entails a reduction of
      the gastric capacity and/or exclusion from the gastrointestinal tract which
      impair nutrients absorption, including dietary iron. Chronic gastrointestinal
      blood loss and iron-losingenteropathy may also contribute to iron deficiency
      after BS. Perioperative anaemia has been linked to increased postoperative
      morbidity and mortality and decreased quality of life after major surgery,
      whereas treatment of perioperative anaemia, and even haematinic deficiency
      without anaemia, has been shown to improve patient outcomes and quality of life.
      However, long-term follow-up data in regard to prevalence, severity, and causes
      of anaemia after BS are mostly absent. Iron supplements should be administered to
      patients after BS, but compliance with oral iron is no good. In addition, once
      iron deficiency has developed, it may prove refractory to oral treatment. In
      these situations, IV iron (which can circumvent the iron blockade at enterocytes
      and macrophages) has emerged as a safe and effective alternative for
      perioperative anaemia management. Monitoring should continue indefinitely even
      after the initial iron repletion and anaemia resolution, and maintenance IV iron
      treatment should be provided as required. New IV preparations, such ferric
      carboxymaltose, are safe, easy to use and up to 1000 mg can be given in a single
      session, thus providing an excellent tool to avoid or treat iron deficiency in
      this patient population.

PMID- 20049367
TI  - [National registry of home enteral nutrition in Spain 2007].
AB  - OBJECTIVE: To communicate the results from the registry of Home-Based Enteral
      Nutrition of the NADYASENPE group in 2007. MATERIAL AND METHODS: We included
      every patient in the registry with home enteral nutrition any time from January
      1st to December 31st of 2007. RESULTS: The number of patients with home enteral
      nutrition in 2007 was 5,107 (52% male) from 28 different hospitals. 95.4% of them
      were 15 yr or older, with a mean age of 67.96 +/- 18.12, and 4.2 +/- 3.38 among
      patients aged 14 yr or less. The most common underlying diseases were
      neurological (37.8%) and neoplastic diseases (29.3%). Enteral nutrition was
      administered p.o. in most patients (63.5%), followed by nasogastric tube (25.9%),
      while gastrostomy was only used in 9.2%. The mean time in enteral nutrition
      support was 9.4 months and the most common reasons for withdrawal were death
      (58.7%) and switching to oral intake (32%). Activity was limited in 31.4% of
      patients and 36.01% were house-bound. Most patients needed partial (26.51%) or
      total (37.68%) care assistance. Enteral formula was provided by hospitals to
      69.14% of patients and by pharmacies to 30.17% of them, while disposable material
      was provided by hospitals to 81.63% and by Primary Care to the remaining
      patients. CONCLUSIONS: In 2007, there has been an increase of more than 30% of
      patients registered with home enteral nutrition comparing with 2006, without any
      big difference in other data, but a higher proportion of patients with enteral
      nutrition p.o.

PMID- 20049368
TI  - [High frequency of non-specific eating disorders in obese persons].
AB  - OBJECTIVES: Determine frequency of Eating Disorders and Non-Specific Eating
      Disorders and pathological behaviour in obese patients. SUBJECTS AND METHODS: The
      study includes fifty-four obese patients (BMI > or = 30) consecutively attended
      at the Nutrition Section of the University Hospital of Vigo. Aged 37.5 +/- 11.1.
      Range 18-58, 45 female and 9 male. CONTROL GROUP: 15 adult normal-weight subjects
      (11 female, 4 male), aged 35,3 +/- 9,2 anos. Frequency of Eating Disorders was
      determined by a lifestyle clinical interview and the following questionnaires:
      Eating Attitudes Test 26 (EAT26), Bulimic Investigatory Test Edimburgh (BITE) and
      Questionnaire Eating Weight Patterns Revised (QEWP-R). RESULTS: Twelve out of 54
      (20.6%) patients showed Pathological Behavior, while 5 (4.1%) and 3 (2.5%) had
      Non- Specific Eating Disorders and Classic Eating Disorders respectively, whereas
      in the control group non subjects showed psychological anomalies. When we divided
      obese patients by the degree of obesity, differences in the frequencies of the
      Eating Disorders was no observed. CONCLUSIONS: In our obese patients,
      Pathological Behavior was the most frequent finding followed for Non-Specific
      Eating Disorders and Classic Eating Disorders.

PMID- 20049369
TI  - [Five-year comparison of two techniques of bariatric surgery in patients with
      morbid obesity followed up in a nurse consultation].
AB  - AIMS: To compare the evolution of weight loss and complications in the patients
      subjected to two techniques of bariatric surgery (RVG: ring vertical gastroplasty
      and BP: gastric by pass type Capella) carried out in HospitalLa Paz during the
      years 2000 and 2001. MATERIAL AND METHODS: 51 patients (27 RVG and 24 BP) were
      operated, and 44 (22 RVG and 22 BP) completed the follow-up at 1 year, 43 (22 RVG
      and 21 BP) at 2 years, and 28 (10 RVG and 18 BP) at 5 years. The parameters
      analyzed at 6, 12, 18, 24 months and 5 years were BMI (body mass index), EI
      (effectiveness index), % LW (percentage of lost weight), % LEW (percentage of
      lost excess of weight), alimentary intolerances, digestive complications,
      surgical complications, physical activity and modification of alimentary habits.
      RESULTS: An important reduction of weight was observed at 6 months with both
      techniques (% LEW: 45.8% with RVG and 53.4% with BP). After 12 months the loss of
      weight was significantly higher with BP (% LEW at 2 years: 59.5% with RVG and 83%
      with BP). However, at 5 years a weight recovery was detected in both groups of
      patients. At 12 months the patients subjected to RVG tolerated worse the meat and
      at 18 months the group of BP tolerated worse the rice. There were not significant
      differences in other parameters. CONCLUSION: The long term results are better
      with BP than with RVG. There is a reduction of effectiveness at 5 years that
      could be related with the modification of alimentary habits and with giving up
      attendance to the nurse consultation.

PMID- 20049370
TI  - Resting energy expenditure in white and non-white severely obese women.
AB  - This study aimed to compare the resting energy expenditure (REE) of white and non
      white severely obese Brazilian women. REE was examined in 83 severely obese
      Brazilian women (n = 58 white and 25 non-white) with mean (+/- SD) age 42.99 +/-
      11.35 and body mass index 46.88 +/- 6.22 kg/m(2) who were candidates for gastric
      bypass surgery. Body composition was assessed by air displacement plethysmography
      (ADP) BOD PODO body composition system (Life Measurement Instruments, Concord,
      CA) and REE was measured, under established protocol, with an open-circuit
      calorimeter (Deltatrac II MBM-200, Datex-Ohmeda, Madison, WI, USA). There was no
      significant difference between the REE of white and non-white severely obese
      women (1,953 +/- 273 and 1,906 +/- 271 kcal/d, respectively; p = 0.48). However,
      when adjusted for fat free mass (MLG), REE was significantly higher in nonwhite
      severely obese women (difference between groups of 158.4 kcal, p < 0.01). REE in
      white women was positively and significantly correlated to C-reactive protein
      (PCR) (r = 0.418; P < 0.001) and MLG (r = 0.771; P < 0.001). In the non-white
      women, REE was only significantly correlated to MLG (r = 0.753; P < 0.001). The
      multiple linear regression analysis showed that skin color, MLG and PCR were the
      significant determinants of REE (R(2) = 0.55). This study showed that, after
      adjustment for MLG, non-white severely obese women have a higher REE than the
      white ones. The association of body composition inflammation factors and REE in
      severely obese Brazilian women remains to be further investigated.

PMID- 20049371
TI  - Choice of diet in patients with anorexia nervosa.
AB  - OBJECTIVE: To analyse the diets chosen by anorexic patients and a control group,
      assessing several nutritional aspects. METHOD: Forty-four outpatients with an
      initial diagnosis of restrictive anorexia nervosa (normal BMI at the time of the
      study) and 34 undergraduates chose their diet from a list of common foods.
      Nutritional content, frequency of consumption, and influence of illness and
      treatment duration on the diet chosen were all analysed. RESULTS: Patients' diets
      had a lower caloric content (P = 0.01). Their diets were also lower in niacin (P
      = 0.03), vitamin B12 (P = 0.04), sodium (P = 0.003), zinc (P = 0.04), phosphorus,
      copper and selenium (P = 0.01). Frequency of consumption was lower among patients
      for bread and cereals, meat and cured meats (P = 0.01), sweet foods (P = 0.001),
      and fatty and fried foods (P = 0.05), but higher for vegetables (P = 0.01).
      DISCUSSION: Patients tend to maintain some characteristic eating patterns and
      modify others, not so much in terms of therapeutic objectives but, rather, as a
      way of following more closely the usual eating patterns of the context.

PMID- 20049372
TI  - [G1359A polymorphism of the cannabinoid receptor gene (CNR1) on anthropometric
      parameters and cardiovascular risk factors in patients with morbid obesity].
AB  - BACKGROUND: A polymorphism (1359 G/A) of the CB1 gene has been described, it was
      reported as a common polymorphism in European populations. The aim of our study
      was to investigate the influence of this polymorphism of CB1 receptor gene on
      obesity anthropometric parameters, cardiovascular risk factors and adipocytokines
      in morbid obese patients. DESIGN: A population of 66 morbid obese patients was
      analyzed. An indirect calorimetry, tetrapolar electrical bioimpedance, blood
      pressure, a serial assessment of nutritional intake with 3 days written food
      records and biochemical analysis (lipid profile, adipocytokines, insulin, CRP and
      lipoprotein-a) were performed. The statistical analysis was performed for the
      combined G1359A and A1359A as a group and wild type G1359G as second group, with
      a dominant model. RESULTS: Thirty eight patients (57.6%) had the genotype G1359G
      (wild type group) and 28 (42.4%) patients G1359A (40.0%) (mutant type group).
      Weight (117.4 +/- 17.4 kg vs 109.4 +/- 13.8 kg: p < 0.05), BMI (45.4 +/- 4.7 vs
      43.3 +/- 3.4: p < 0.05), fat mass (60.1 +/- 13.4 kg vs 53,6 +/- 12.8 kg: p <
      0.05), waist circumference (126.3 +/- 10.8 cm vs 122.9 +/- 12.6 cm: p < 0.05), C
      reactive protein (11.2 +/- 8.8 mg/dl vs 7.8 +/- 4.6 mg/dl: p < 0.05), insulin
      (23.5 +/- 19.8 mUI/L vs 18.4 +/- 17.1 mUI/L: p < 0.05) and HOMA (6.46 +/- 6.2 vs
      4.70 +/- 4.6: p < 0.05) were lowers in patients with G1359A genotype. No
      differences were detected between groups in other parameters. CONCLUSION: The
      mutant genotype G1359A is associated with a better cardiovascular profile
      (weight, BMI, fat mass, waist circumference, insulin, HOMA and c reactive
      protein) than wild type group.

PMID- 20049373
TI  - Social and behavioural aspects and their consequences in obese teenagers:
      importance of family's history.
AB  - OBJECTIVES: Overweight, the metabolic syndrome and accompanying diseases are
      dramatically increasing problems. We investigated social and behavioral variables
      that influence overweight in adolescents and tested their influence on plasma
      markers related to diabetes and endothelial dysfunction. METHODS: 79 male
      adolescents were enrolled (age 13-17 years). Endothelial progenitor cells were
      counted by flow cytometry. Adiponectin and soluble E-selectin (sEselectin) were
      determined by ELISA. RESULTS: Body weight differs significantly if the family's
      history was positive for arterial hypertension (p < 0.001), diabetes (p < 0.001),
      hypercholesterolemia (p<0.001), and coronary artery disease (CAD, p < 0.01). The
      hours of physical activity represent a predictor of BMI in linear regression
      analysis (p < 0.001; R(2) = 0.195). Markers for endothelial damage are altered in
      adolescents with positive family history for hyperlipidemia and CAD. CONCLUSION:
      The family's history is an important variable influencing the body weight of
      teenagers. Via obesity and independently, it influences the early development of
      endothelial damage. It might serve to detect teenagers at risk for appropriate
      intervention.

PMID- 20049374
TI  - Comparison of the ActiGraph accelerometer and Bouchard diary to estimate energy
      expenditure in Spanish adolescents.
AB  - INTRODUCTION: The aim of this study was to evaluate the agreement between the
      ActiGraph accelerometer and the Bouchard diary to estimate energy expenditure
      (EE) in a Spanish adolescent population. METHODS: Sixty-one Spanish adolescents,
      aged 12-16 years, were recruited for this study. The Bouchard diary and the
      ActiGraph were administered for 3 consecutive days. EE estimated by the Bouchard
      diary was calculated using 2 different MET category values (BD-Bouchard and BD
      Bratteby). EE estimated by the ActiGraph was calculated using 3 predictive
      equations (AC-Trost, AC-Freedson, and AC-Ekelund). Participants with complete 24
      h data were also analyzed to control the possible loss of accuracy. Agreement was
      examined by Pearson and concordance correlations, paired t-test, and Bland-Altman
      method. RESULTS: Thirty-seven adolescents were included in the analyses with
      complete 72 h. Relationships between EE calculated by the Bouchard diary and the
      ActiGraph were high (ranged: r = 0.61-0.78). Concordance correlations were
      moderate (r c = 0.60) by BD-Bratteby and AC-Trost, and low using BD-Bratteby and
      AC-Ekelund (r c = 0.15). EE estimated by BD-Bratteby and AC-Trost also showed no
      significant differences (P> 0.05) and absolutely agree 0.0 +/- 5.0 MJ/d (95%
      confidence interval: +/- 0.90 MJ/d), but with wide limits of agreement (+/- 9.80
      MJ/d). Relationships were higher and differences were smaller in the 72 h sample
      than in the 24 h sample. CONCLUSIONS: The Bouchard diary and the ActiGraph showed
      high relationships, moderate concordance, and large differences to estimate EE in
      Spanish adolescents. Advantages, disadvantages, and agreements between both
      instruments must be taking into consideration for health-related research.

PMID- 20049375
TI  - Artificial Nutritional Support Registries: systematic review.
AB  - INTRODUCTION: The nutritional registries are data bases through which we obtain
      the information to understand the nutrition of populations. Several main
      nutrition societies of the world have these types of registries, outstanding the
      NADYA (Home artificial and Ambulatory nutrition) group in Spain. The object of
      this study is to determine by means of a systematic review, the existent
      scientific production in the international data bases referred to nutritional
      support registries. METHODS: Descriptive transversal study of the results of a
      critical bibliographic research done in the bioscience data bases: MEDLINE,
      EMBASE, The Cochrane Library, ISI (Web of Sciences), LILACS, CINHAL. RESULTS: A
      total of 20 original articles related to nutritional registries were found and
      recovered. Eleven registries of eight countries were identified: Australia,
      Germany, Italy, Japan, Spain, Sweden, United Status and United Kingdom. The Price
      Index was of 65% and all the articles were published in the last 20 years.
      CONCLUSIONS: The Price Index highlights the innovativeness of this practice. The
      articles related to nutritional support are heterogeneous with respect to data
      and population, which exposes this as a limitation for a combined analysis.

PMID- 20049376
TI  - Chemopreventive response of diclofenac, a non-steroidal anti-inflammatory drug in
      experimental carcinogenesis.
AB  - The chemopreventive response was evaluated of nonsteroidal anti-inflammatory
      drug, Diclofenac, a preferential cyclooxygenase-2 (COX-2) inhibitor in 1,2
      dimethyhydrazine (DMH)-induced colon cancer in rat model. The signs of neoplasm
      were evident in the animals receiving 30mg of DMH per kg body weight in a weekly
      s.c injection for six weeks. The putative biomarker of carcinogenesis was visible
      in the form of multiple plaque lesions in DMH treatment and then regression seen
      in those animals which also received an oral dose of Diclofenac, 8 mg/kg body
      weight whereas no such macroscopic neoplastic lesions were seen in the animals
      receiving Diclofenac only or the control animals receiving the vehicle of the
      drug. Histopathological results showed the presence of early aberrant changes in
      the form of severe dysplasia and also numerous crypt fissions in the apical
      surface of the colonic mucosa. A very high expression of COX-2 was seen in the
      colonic epithelium of DMH-treated rats, as analyzed by immunohistochemistry.
      Also, the apoptotic events were assessed by terminal deoxynucleotidyl dUTP nick
      end labeling (TUNEL) assay, where the DMH group shows few number of TUNEL
      positive cells which dramatically increased in the Diclofenac treatment. The
      results suggest that Diclofenac could be an effective chemopreventive agent in
      colon cancer, where perhaps apoptosis plays a very dominant end effect in cancer
      cell killings.

PMID- 20049377
TI  - [Validation of MNA scale score as a nutritional risk factor in institutionalized
      geriatric patients with moderate and severe cognitive impairment].
AB  - INTRODUCTION: comprehensive geriatric assessment includes examination of the
      nutritional status given the high prevalence of hyponutrition in this kind of
      patients, particularly in patients with associated cognitive impairment. Scales
      for screening the nutritional status include questions on self-perception
      difficult to answer by demented elder patients. OBJECTIVE: To study the
      specificity, the positive predictive value, and the sensitivity of the MNA scale
      to detect malnutrition in patients diagnosed with Alzheimer's disease with
      advanced cognitive impairment. MATERIAL AND METHODS: a population-based
      descriptive study with a sample of 52 patients older than 70 years,
      institutionalized, and with moderate-severe Alzheimer's disease was designed. The
      sensitivity, specificity, and positive predictive value of MNA scale were studied
      regarding the parameters on malnutrition of the American Institute of Nutrition
      (AIN). RESULTS: the sensitivity, specificity, and positive predictive values were
      60%, 94.7%, and 93.8%, respectively. There was a significant correlation (p <
      0.001) between the score obtained with the MNA Scale and the Tinneti's Risk of
      Fall Scale (r = 0.577), the Barthel's function (r = 0.742), the MCT cognitive
      assessment (r = 0.651), and creatinine levels (r = 0.402). More than 50% of the
      sample presented at least one malnutrition parameter altered. CONCLUSIONS: the
      MNA Scale presents lower sensitivity and specificity in these patients. Designing
      a nutritional assessment scale without subjective evaluations and only with
      objective parameters might improve its efficiency in institutionalized elderly
      patients with moderate-severe cognitive impairment.

PMID- 20049378
TI  - [Population wills about the decisions and cares at the end of life].
AB  - OBJECTIVE: To know the wishes and willings of the general population at the end
      of life under the assumption of suffering a terminal disease. METHOD: Crosswise
      quanti-qualitative study. An opinion poll has been made under the assumption of
      suffering a terminal disease with 10 questions about the wishes of the population
      at the end of life Descriptive techniques have been used as well as chi(2)
      Pearson, chi(2) Fisher and Student's T tests for the analysis. Also, analysis of
      the comments contents techniques have been used. RESULTS: 403 polls have been
      analyzed with an age mean of 38.2 years. 63.8% of the people prefer to end their
      life at home IC 95%, [59.1%-68.5%]. The majority prefer their partners as care
      giver 43.4% IC 95% [38.6-48.3]. The 85.9% IC 95% [82.5-89.3] would not wish to be
      undergone to either resuscitation maneuvers or other ways to extend their lifes
      to the maximum. The 49.4% IC 95% [44.5-54.3] would want to receive special
      nutritional support. CONCLUSIONS: It was observed that the oldest population
      refuses to talk about their own death. The vast majority of the polled people
      would want to die at home with their partner's cares. Half of the people want to
      be feed artificially until the end of their days.

PMID- 20049379
TI  - [Dietary modifications, in young Muslims engaged in Ramadan fasting].
AB  - The practice of the Islamic precept of Ramadan (R) imposes to those who practice
      it important physiological and psychological changes due to the water and dietary
      restrictions they are subjected to, which has a particular impact on the Muslim
      students' physical and psychological performances, particularly in multicultural
      Western societies, where there are no schedule adjustments in daily activities.
      Among the changes in lifestyle, consequently, the dietary changes are stressed,
      both qualitative and quantitative. Due to the importance of this issue and facing
      the limited knowledge the Muslim teenagers who live in non-Islamic societies have
      about the effects of Ramadan, it is suggested as main objective of this study the
      analysis of changes in nutrients during R in a group of Muslim students of both
      sexes, in order to solve and prevent some of the problems shown in this period.
      MATERIALS AND METHODS: 55 Muslim youngsters were selected (24 men and 31 women)
      aged between 15 and 18, who practise R; and the diet was analysed by inventory
      over 3 days, one week before fasting and in the second week during it. RESULTS:
      In R there are no relevant changes in caloric intake. The consumption of
      carbohydrates and proteins is increased, and that of fat is decreased.
      DISCUSSION: the changes in R lead to a diet more regulated to nutritional
      recommendations; and to this seems to have contributed the fact that the
      participants took their meals at home, where, in spite of the Western cut of the
      population, it is felt an important influence of North African traditions and
      habits, due to its border contact with Morocco.

PMID- 20049380
TI  - [Effectiveness of dietetic treatment in nephrotic syndrome].
AB  - We present the case of a male patient suffering from a primary amyloidosis and a
      nephrotic syndrome who came to dietotherapy clinic. In the first visit we made a
      nutritional record including an anthropometric evaluation, body composition,
      biochemistry, and food intake. The patient had an excess of body water,
      proteinuria, low plasma protein, albumin, prealbumin and HDL cholesterol levels,
      and high concentrations of total cholesterol, LDL and triglycerides. The
      consumption of protein and sodium was higher than the recommendation. An
      individualized diet was made. Six months later, his weight and the excess of body
      water decreased, but the fat free mass remained unchanged. The levels of albumin
      and prealbumin increased, the proteinuria decreased. Total cholesterol, LDL and
      triglycerides decreased until normal levels. Dietetary treatment in nephrotic
      syndrome is effective to decrease proteinuria, improve cholesterol and
      triglycerides levels, and to prevent malnutrition.

PMID- 20049381
TI  - [Postsurgical chylous ascites: case report and literature review].
AB  - Chylous ascites derives from chyle leakage into the peritoneal cavity, either due
      to rupture or obstruction of abdominal lymphatic vessels. The main clinical sign
      is abdominal distention, while diagnosis requires the presence of triglycerides
      in ascitic fluid. Neoplasms are the most common cause of chylous ascites,
      although less common causes, such as abdominal surgery, should also be
      considered. The mainstay of therapy is hyperproteic diet with fat restriction and
      middle-chain triglycerides. Parenteral nutrition is reserved for cases in which
      dietary treatment fails to restore an optimal nutritional status or is
      contraindicated, whereas surgery is considered for patients that are deemed
      refractory to conservative therapy. We present a case of chylous ascites
      secondary to retroperitoneal lymphadenectomy.

PMID- 20049382
TI  - [There is a relationship between nutritional status assessed by anthropometry and
      family typology in Mexican children between one and four years old].

PMID- 20049383
TI  - Long term effect of Mediterranean diet on weight loss.

PMID- 20049384
TI  - Evidence of improvement of the prescription standard and cost reduction with the
      use of special nutritional formulae in Rio Grande do Sul state/Brazil after
      implementation of a reference center.

PMID- 20049385
TI  - [Complications of enteral nutrition in a patient with gastrostomy].

PMID- 20049386
TI  - Weight concerns and weight reduction practices of Portuguese adolescents.

PMID- 20049387
TI  - [Mediterranean diet and adolescents].

PMID- 20049388
TI  - [Home parenteral nutrition in pediatric cystic fibrosis patients].

PMID- 20049389
TI  - [Archivos in Vancouver and Brasilia].

PMID- 20049390
TI  - [The difficult diagnosis of a simple pneumonia].

PMID- 20049391
TI  - [The clinic of the word].

PMID- 20049392
TI  - [Hypercholesterolemia reduction in children and adolescents after two years of
      intervention].
AB  - INTRODUCTION: Hypercholesterolemia, one of the main risk factors for
      cardiovascular diseases, can be detected since childhood. The early detection and
      a suitable educational process would allow to generate changes of habits and to
      decrease its prevalence. In 2003, total cholesterol (TC) > 170 mg/dl was found in
      39.2% school children and adolescents, aged 5-17 years, of Jovita, Cordoba.
      OBJECTIVE: To assess cholesterol levels decrease after an educational process and
      to analyze the relation between hypercholesterolemia and family history for
      cardiovascular diseases. METHODS: Formal and no formal educational intervention
      was developed for two years, through curricular adaptations, talks, campaigns in
      radio and TV, graphic press, drama, workshops and leaflets. In 2005, cholesterol
      level was assessed, along with a survey on changes of nutritional habits and
      physical activity, and family history. RESULTS: A group of 161 students was
      assesses in both opportunities. There was a significant reduction in total
      cholesterol (average 13 mg/dl; p< 0.0000), 51 students (31.7%) normalized their
      TC values (<170 mg/dl). The effect of regression to the average was 3 mg/dl. In a
      group of 66 students with TC > 199 mg/dl, the variations of the averages were:
      TC= -21 mg/dl, LDL-C= -16 mg/dl. The survey revealed improvements in the habits;
      family history was positive in 59%, unknown in 14%, and negative in 27%, the last
      ones had the best response to the intervention. CONCLUSION: A significant
      reduction of TC was obtained in the studied population; this may be due to the
      educational intervention. More than a quarter of the individuals presented
      negative family history for cardiovascular risk factors. Decrease in TC was
      proportionally better in this group than in those with positive family history.

PMID- 20049393
TI  - [Feeding practices in children aged under 2 years].
AB  - INTRODUCTION: Good feeding practices allow to begin and to achieve healthy life
      styles. OBJECTIVES: To determine the duration of breastfeeding and age of
      introduction of complementary feeding, its type, composition of the meal and
      adults who provide it, in healthy children younger than 2 years in the provinces
      of Mendoza, San Juan and San Luis. To ascertain the social and demographic
      factors associated with them. POPULATION AND METHODS: Cross-sectional descriptive
      study. A voluntary group of pediatricians from the Cuyo Region of Argentina
      Paediatrics Society administered a survey on feeding practices in healthy
      children. RESULTS: 741 surveys were obtain, 51.41% in public's institution.
      Children's age: 11.3 +/- 6.1m. Feeding practices at the time of survey: 66.53%
      were breastfeeding; of the ones who were not breastfed: 95.12% had been
      breastfed, during: 7.8 +/-5.2m. The youngest mothers showed more breastfeeding
      frequency. Children received: mush/porridge from 6m in 64.24%, enriched with oil,
      milk and cheese; meats: 73.28% from 7.8 +/- 2.1m (rank 3-19) and eggs: 60.19%
      from 8.4 +/- 2.6m (rank 3-20); sweetened beverages from 10.49 +/- 3.52 m. First
      meal was offered by mother (88.72%) and she was usually in charge of feeding
      (91.44%). The TV was turned on during the meals at 50.87%. CONCLUSION:
      Breastfeeding was a frequent practice, greater in youngest mother. They were
      common: beginning of complementary feeding at 6 months, enrichment of the first
      meal; wide range of incorporation of eggs and meats, early incorporation of
      sweetened drinks and exposition to TV during the meal time. Usually, the mother
      was the one who fed the children.

PMID- 20049394
TI  - [Factors related to the approval, development and publication of research
      protocols in a paediatric hospital].
AB  - BACKGROUND: Unpublished research is a frequent and reported problem. Objective.
      To analyze factors associated to approval, development and publication of
      research protocols submitted to Hospital Garrahan Institutional Review Board.
      METHOD: Descriptive and observational study. The characteristics from every
      protocol submitted to the IRB (January/2001 to June/2006) were collected and a
      questionnaire was administered in order to explore the accomplishment of the
      study, meeting presentations, publications or mainspring for not-publication. We
      calculated OR and 95% CI to estimate what factors were related to the approval
      and the publication of the studies. RESULTS: 190 research protocols were
      evaluated; 125 (66%) were approved; 84 protocols were carried out (44%) and 40
      (21%) were published. The approval was related to basic research (OR 8,6 95%CI
      2.3-29) and fellowship participation (OR 9.4 95%CI 4-21.7); although,
      experimental design (OR 0.76 95%CI 0.61-0.96) and financial support by
      pharmaceutical industry (OR 0.19 95%CI 0.06-0.60) decreased approval odds. The
      main cause for not publication was the lack of time for the writing of the
      article. We have not found factors related to the publication. CONCLUSION: From
      the presentation of a protocol up to its approval and publication there exists
      barriers that decrease progressively the possibility of completing the research.

PMID- 20049395
TI  - [Overdiagnosis of amebiasis in children with dysentery].
AB  - INTRODUCTION: There are morphologically identical amebaes, but with differences
      that can distinguish them; one as pathogenic: Entamoeba histolytica, and the
      other: Entamoeba dispar, as inoffensive. That brought the new hypothesis that
      many of the cases treated as amebiasis, weren't so. OBJECTIVE: To identify E.
      hystolitica in patients with dysentery, supposed to be caused by amebae. METHODS:
      Transversal and observational study performed between March 2005 and November
      2007 in the city of Santa Fe, Argentina. Stools from children aged 2 months to 15
      years-old with dysentery and direct exams with E. hystolitica/ dispar, were
      studied with ELISA to detect the adhesin of E. histolytica (adhesin Eh).
      Permanent stains for amebae were done as well as stool cultures. Clinical data
      were charted. RESULTS: 75 children were studied; 35 were male and 40, female,
      with a median age of 3 years-old. All of them presented diarrhea with leucocyte,
      73% macroscopic blood on stool and 27% detectable on the microscope. Elisa Eh was
      positive in 21; 3 cases had hematophagous trophozoites. In 15 stool cultures were
      found: S. flexneri S2 type in 5 cases. Other parasites: 6 (Blastocystis homini
      5). In 54 adhesin Eh was negative, 19% of the coulouring detected E. dispar. From
      44 stool cultures: S. flexneri S2 type was detected in 13, Shigella sp in 1, C
      jejuni 5, other: 3. Other parasites: 12 (Blastocystis homini 9). CONCLUSION: In
      this group of children with "amebic dysentery", half of them developed invasive
      bacteriae and only 28% had E. histolytica on stools; that means that the
      prevalence of positive cases in the population could be 18% to 38% [CI 95%
      (0.179; 0.381)].

PMID- 20049397
TI  - [Perinatal bioethics: euthanasia or end-of-life decisions? Analysis of the
      Groningen Protocol].
AB  - The so called "Groningen Protocol" was conceived as a framework to discuss the
      euthanasia in neonates. Originally, it presents three groups of babies who might
      be candidates to this option. We analyzed the protocol in its original context
      and that of the Dutch society in which it was created. The analysis started with
      a careful reading of the protocol in both English and Dutch versions, translated
      later into Spanish. The medical and nursing staff participated in discussing it.
      A final consensus was reached. The Institutional Ethics Committee at our hospital
      discussed it freely and made recommendations for its application as a guideline
      to honestly discuss with parents the clinical condition of their babies, without
      permitting the option included literally in the word euthanasia. We selected four
      extremely ill infants. Their parents were interviewed at least twice daily: three
      stages were identified: the initial one of promoting all possible treatments; a
      second one of guarded and cautious request for the staff to evaluate "suffering",
      and a last one where requests were made to reduce therapeutic efforts to provide
      dignified death. A week after the death of their infants, they were presented
      with the facts of the protocol and the limits of our legal system. In all four
      cases the parents suggested that they would have chosen ending the life of their
      infants, in order to avoid them undue suffering. They clearly pointed out that
      this option emerged as a viable one to them once the ultimate outcome was
      evident. The protocol must not be viewed as a guideline for euthanasia in
      newborns, but rather as a mean to discuss the critical condition of an infant
      with the parents. Its direct implementation in our setting remains difficult. As
      a clear limitation for its overall application remains the definition of what is
      considered "unbearable suffering" in newborns, and how to certify when the infant
      has "no prospect". We emphasize the benefits of securing the help of the Ethics
      Committee and of "second opinions" from authorized physicians.

PMID- 20049396
TI  - [Estimated prevalence of musculoskeletal pain in children, who attend a community
      hospital].
AB  - INTRODUCTION: Musculoskeletal pain is a common symptom in childhood. It is
      estimated that 5 to 19% of healthy children experience musculoskeletal pain.
      AIMS: To estimate the prevalence of musculoskeletal pain and to describe
      epidemiological characteristics in children 3 to 12 years of age, who attend a
      community hospital. POPULATION, MATERIAL AND METHODS: This is an observational
      transversal study. A self-administered questionnaire was completed in the waiting
      room of the Pediatric ambulatory area. Children with chronic diseases were
      excluded. Statistical tests used included chi(2) test, Mc Nemar and a logistic
      regression model analysis. RESULTS: A total of 240 questionnaires were
      distributed and 229 were returned. Median age of children was 6 years and 36 (25
      50) years in their mothers. Fifty four percent were girls. Pain was present in
      21.4% in the last year, and 19.2% in the past 3 months, both groups were
      concordant (Mc Nemar test not significant). Associated factors with pain in the
      last year were: age and family history of current pain and during childhood
      (logistic regression model). No relation was found with sex of the child, mother
      age, mono-parental family, siblings or stress family factors in the last year.
      The musculoskeletal pain was localized in: lower limbs (66%), muscles (52%),
      joints (38%) and was bilateral in 33%. In 40% of children the pain duration was
      transient (minutes), 55% developed pain, at least, once a month and in 51% was
      related to exercise. Limitation of daily living activities due to pain was seen
      in 16%. The pain resolved spontaneously in 50%. Pediatricians were consulted in
      63% of the cases and 8% consulted in Orthopedics. When comparing the pain pattern
      in 2 groups of children (< and > 6 years), we found that older children tended to
      present pain more than once a month and related to exercise. CONCLUSIONS: The
      prevalence of musculoskeletal pain was 21.4%. Pain was associated to child age
      and family history of musculoskeletal pain. Pain was referred to lower limbs
      (mainly muscles), periodic (more than once a month) and related to exercise.

PMID- 20049398
TI  - [Evidence-based pediatrics: diagnostic tests (1st part)].
AB  - To arrive to an accurate diagnosis is a great challenge in medical daily
      practice. Through anamnesis and physical examination, it is possible to have a
      clinical suspicion but it is often required a diagnosis test to confirm or rule
      out it. For the same condition, technological advances have multiplied the
      available tests. From them, doctors have to choose the most suitable test,
      according to its performance, patient characteristics, harms and costs. We will
      analyze the reliability, interpretation and application for one diagnosis test
      results.

PMID- 20049399
TI  - [Juvenile idiopathic arthritis: Part 2. Prognosis and current therapeutic
      approach].
AB  - The prognosis of juvenile idiopathic arthritis has improved substantially during
      the last decade, due to an earlier recognition of the disease, its predictors of
      outcome and the approach to treatment. The introduction of biological agents,
      constitutes a valuable treatment option for children who are resistant or
      refractory to conventional antirheumatic drugs. Disease outcome regarding
      different categories, predictors associated to poor prognosis and the current
      approach to treatment are reviewed in this article.

PMID- 20049400
TI  - [Optic nerve hypoplasia and septo-optic dysplasia].
AB  - The septo-optic dysplasia or De Morsier syndrome is an unusual disorder of the
      embryonic development. It consists of hypoplasia in one or both optic nerves,
      midline cerebral malformations and hypothalamic-pituitary dysfunction, which is
      inconstant. The present work describes the findings of 9 patients with septo
      optic dysplasia.

PMID- 20049401
TI  - [Transpyloric feeding tube placement by gastric air insufflation technique in
      pediatric intensive care patients].
AB  - INTRODUCTION: The aim of the study was to evaluate the success rate of
      transpyloric tube (TPT) placement using air gastric insufflation technique in
      patients hospitalized in the Pediatric Intensive Care Unit. POPULATION, MATERIALS
      AND METHODS: The data were collected retrospectively from a prospective filled
      database. TPT positioning was defined as successful by evaluation of its distal
      end in the abdominal X-ray. Demographic information, success rate, duration of
      the procedure were registered. Descriptive statistics was used to analyze the
      data. RESULTS: There were 37 procedures in 33 patients and 84% of them were on
      mechanical ventilation. The percentage of success in TPT placement was 89%
      (33/37) and the mean duration of the procedure was 12.8 min +/- 5.3. No
      complications were registered. CONCLUSION: TPT placement through the insufflation
      of air in the stomach is a short, simple, effective, and well tolerated procedure
      that can be done at bedside.

PMID- 20049402
TI  - [Hepatitis and coagulopathy secondary to neonatal enteroviral infection].
AB  - Enteroviruses cause a wide spectrum of clinical manifestations in neonates, from
      asymptomatic infection to severe and fulminant, sometimes fatal disease. A septic
      disease is the clinical manifestation of one fourth of the cases in neonates,
      with multiorganic affection. Hepatitis and coagulopathy are related to bad
      prognosis, generally associated to catastrophic hemorrhages. In those cases, an
      aggressive support therapy and correct administration of platelet and clotting
      factor replacement is necessary. The liver, in survivors, frequently has
      sufficient regenerative capacity to allow normalization of hepatic function and
      adequate growth of the child. We present the case of a newborn who developed
      hepatitis and coagulopathy secondary to an enteroviral infection, with total
      recovery and absence of hemorrhagic complication. Her mother had a febrile
      syndrome 24 hours ante partum.

PMID- 20049403
TI  - [Citrobacter koseri brain abscess in an infant: case report and literature
      review].
AB  - We present a 2 month-old female infant admitted to the hospital with macrocephaly
      as main clinical sign, irritability, and vomiting. The computer tomography
      scanning showed a cystic frontal image with contralateral ventricle displacement.
      Surgical intervention was performed. Purulent material culture was positive for
      Citrobacter koseri (diversus). Cerebrospinal fluid culture was negative. The
      infant was treated with antibiotics for 6 weeks with a good outcome. She
      presented postsurgical hydrocephaly and required ventriculoperitoneal valve.

PMID- 20049404
TI  - [National Program on Pediatric Actualization (PRONAP): field works reports on the
      years 2003, 2005, and 2006].
AB  - PRONAP is a distance learning course from the Argentine Society of Paediatrics
      whose primary aim is contributing to improve the child/mother health. Annually,
      participants perform a field work. The subject in 2003 was "Deficiency,
      Disability, and Disablement". In the year 2005, a personal survey on tobacco use
      and knowledge on second-hand smoking was realized; another survey, to parents of
      ten 5-year-old children, was carried on regarding home exposition to ambience
      tobacco smoke. In 2006, the work deals with uremic-haemolytic syndrome and
      included survey implementations. The main results of these three works are
      presented.

PMID- 20049405
TI  - [Previous issue clinical case presentation: HSV infection (type 1)].

PMID- 20049407
TI  - [A normalized ethics is not ethics].

PMID- 20049409
TI  - IL-2 -330 T/G SNP and serum values-potential new tumor markers in neuroendocrine
      tumors of the gastrointestinal tract and pancreas (GEP-NETs).
AB  - Cytokines participate in tumorigenesis of gastroenteropancreatic neuroendocrine
      tumors (GEP-NETs). Single nucleotide polymorphisms (SNPs) in cytokine genes
      influence expression of proteins and are evaluated in cancer susceptibility. The
      aim of this study was to evaluate IL-2 -330 T/G SNP and susceptibility to GEP
      NETs, and analyze the correlation between G-allele and IL-2 serum values in GEP
      NET patients. Moreover we assessed the value of IL-2 as a tumor serum marker. IL
      2 -330 T/G SNP was examined in 101 patients and 150 healthy volunteers and IL-2
      serum levels in patients and 20 controls. Patients' IL-2 serum levels were
      compared to IL-2 -330 T/G genotypes and tumor functional status and finally with
      known markers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid (5
      HIAA). There was a significant difference in genotype distribution of the IL-2 
      330 polymorphisms between GEP-NET and control group (p = 0.0006) as well as in
      the frequency of G-allele (p = 0.010). G-allele correlated with higher IL-2 serum
      levels (p = 0.028) and elevated in all patients, being highest in patients with
      functional tumors (p = 0.039). Compared to CgA and 5-HIAA, IL-2 was more specific
      in detecting GEP-NET patients (p < 0.0001 and p < 0.0001, respectively). Our
      results indicate importance of IL-2 in GEP-NET development and biochemical
      diagnosis.

PMID- 20049410
TI  - A functionally relevant IRF5 haplotype is associated with reduced risk to
      Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG), characterized by systemic vasculitis and
      granulomatous inflammation, is a rare chronic rheumatic condition potentially
      sharing some etiopathological principles with other autoimmune disorders, e.g.,
      rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Several large
      association studies have identified genetic risk factors for RA and SLE. Thereof,
      we have evaluated the relevance of the most promising ones in WG. 22 single
      nucleotide polymorphisms (SNPs) within or in the vicinity of CCL21, CD40, CDK6,
      IL21, IL2RB, IRF5, KIF5A, KLF12, MMEL1, PRKCQ, STAT4, TNFAIP3, and TRAF1/C5 have
      been genotyped in >600 German WG cases and >800 matched controls. While most
      polymorphisms did not show suspicious effects on WG susceptibility, SNPs
      representing TNFAIP3 (rs6922466, p = 0.032, odds ratio (OR) 0.83, 95% confidence
      interval (CI) 0.7--0.98) and CDK6 (rs42041, p = 0.0201, OR 1.21, 95% CI 1.03
      1.43) revealed nominally significant differences in allele distribution. The
      strongest association was detected for a functionally relevant four SNP haplotype
      of IRF5, which comprised a protective effect (p = 0.0000897, p (corrected) =
      0.0012, OR 0.73, 95% CI 0.62-0.85) similar to those previously seen in RA and
      SLE. Thus, we suggest that WG, SLE, and RA share some, but not many, genetic risk
      factors, which supports models of partly overlapping etiopathological mechanisms
      in these disorders.

PMID- 20049411
TI  - Antibody and cell-mediated immunity to Streptococcus pneumoniae: implications for
      vaccine development.
AB  - It has long been assumed that children develop natural immunity to pneumococci
      via the acquisition of anticapsular antibodies, which confers serotype-specific
      immunity to the organism. This view has been further reinforced by the recent
      success of capsular polysaccharide conjugate vaccines in children in reducing
      colonization and disease caused by vaccine-type strains. Less clear, however, is
      whether this mechanism is responsible for the age-related gradual increased
      resistance to pneumococcal carriage and disease. Recent epidemiologic and
      experimental evidence point to the possibility that another mechanism may be
      involved. Here, an alternative possibility is presented, whereby it is proposed
      that acquired immunity to this common human pathogen is derived not only from
      natural acquisition of antibodies (capsular and noncapsular) that provides
      protection against invasive disease but also from the development of pneumococcus
      specific CD4+ T(H)17 cells that reduces the duration of carriage and may also
      impact mucosal disease. This review focuses on the experimental and clinical
      evidence in support of this hypothesis. The implications for future vaccine
      development against Streptococcus pneumoniae are also discussed.

PMID- 20049413
TI  - A novel locus for soybean aphid resistance.
AB  - The soybean aphid (Aphis glycines Matsumura) is an important pest on soybean
      [Glycine max (L.) Merr.] in North America. Aphid resistance has recently been
      found on plant introduction (PI) 567543C, but little is known about its genetic
      control. The objectives of this study were to identify the resistance genes in PI
      567543C with molecular markers and validate them in a different genetic
      background. A mapping population of 249 F(4) derived lines from a cross between
      PI 567543C and a susceptible parent was investigated for aphid resistance in both
      the greenhouse and the field. The broad sense heritability of aphid resistance in
      the field trial was over 0.95. The segregation of aphid resistance in this
      population suggests a major gene controlling the resistance. Bulked segregant
      analysis with molecular markers revealed a potential genomic region. After
      saturating this putative region with more markers, a genetic locus was mapped in
      an interval between Sat_339 and Satt414 on chromosome 16 (linkage group J) using
      the composite interval mapping method. This locus explained the majority of the
      phenotypic variation ranging from 84.7% in the field trial to 90.4% in the
      greenhouse trial. Therefore, the aphid resistance in PI 567543C could be mainly
      controlled by this gene. This aphid resistance gene was mapped on a different
      chromosome than the other resistance genes reported previously from other
      resistant germplasms. This gene appears to be additive based on the aphid
      resistance of the heterozygous lines at this locus. Thus, a new symbol Rag3 is
      used to designate this gene. Moreover, Rag3 was confirmed in a validation
      population. This new aphid-resistance gene could be valuable in breeding aphid
      resistant cultivars.

PMID- 20049412
TI  - Community-associated methicillin-resistant Staphylococcus aureus immune evasion
      and virulence.
AB  - Staphylococcus aureus is a significant cause of human infections globally.
      Methicillin-resistant S. aureus (MRSA) emerged in the early 1960s and is now
      endemic in most healthcare facilities. Although healthcare-associated MRSA
      infections remain a major problem in most industrialized countries, those caused
      by community-associated MRSA (CA-MRSA) are now the most abundant cause of
      bacterial infections in the community in some parts of the world, such as the
      United States. The basis for the emergence and subsequent success of CA-MRSA is
      incompletely defined. However, the ability of the pathogen to cause disease in
      otherwise healthy individuals is likely attributed, in part, to its ability to
      circumvent killing by the innate immune system, which includes survival after
      phagocytosis by neutrophils. In this review, we discuss the role of neutrophils
      in host defense against S. aureus and highlight progress made toward
      understanding mechanisms of CA-MRSA virulence and pathogenesis.

PMID- 20049414
TI  - Evidence for genetic differentiation and divergent selection in an autotetraploid
      forage grass (Arrhenatherum elatius).
AB  - The use of local provenances in restoration, agriculture and forestry has been
      identified as measure to sustain biological diversity and to improve local
      productivity. However, the delineation of regional provenances is challenging
      because it requires the identification of well-defined groups based on
      spatiogenetic differentiation and/or the evidence of local adaptation. In this
      study, we investigate genetic variation at 186 AFLP loci in 46 European
      accessions of the important grassland species Arrhenatherum elatius and ask (1)
      whether genetic variation within accessions differs between European geographical
      regions; (2) at which spatial scale populations are structured across Europe and
      (3) whether putatively adaptive markers contribute to this pattern and whether
      these markers can be related to climatic site conditions. Basic expectations of
      population genetics are likely to be altered in autotetraploid species, thus, we
      adopted a band-based approach to estimate genetic diversity and structuring.
      Compared to other grasses A. elatius showed high genetic diversity and
      considerable differentiation among accessions (Phi(ST) = 0.24). Accessions
      separated in a Western European and a Central/Eastern European group, without
      further structure within groups. A genome scan approach identified four
      potentially adaptive loci, whose band frequencies correlated significantly with
      climatic parameters, suggesting that genetic differentiation in A. elatius is
      also the result of adaptive processes. Knowledge on adaptive loci might in the
      long run also help to adapt ecosystems to adverse climate change effects through
      assisted migration of ecotypes rather than introduction of new species.

PMID- 20049415
TI  - Optimal dietary approaches for prevention of type 2 diabetes: a life-course
      perspective.
AB  - In recent years, several alternative dietary approaches, including high-protein
      and low-glycaemic-load diets, have produced faster rates of weight loss than
      traditional low-fat, high-carbohydrate diets. These diets share an under
      recognised unifying mechanism: the reduction of postprandial glycaemia and
      insulinaemia. Similarly, some food patterns and specific foods (potatoes, white
      bread, soft drinks) characterised by hyperglycaemia are associated with higher
      risk of adiposity and type 2 diabetes. Profound compensatory hyperinsulinaemia,
      exacerbated by overweight, occurs during critical periods of physiological
      insulin resistance such as pregnancy and puberty. The dramatic rise in
      gestational diabetes and type 2 diabetes in the young may therefore be traced to
      food patterns that exaggerate postprandial glycaemia and insulinaemia. The
      dietary strategy with the strongest evidence of being able to prevent type 2
      diabetes is not the accepted low-fat, high-carbohydrate diet, but alternative
      dietary approaches that reduce postprandial glycaemia and insulinaemia without
      adversely affecting other risk factors.

PMID- 20049416
TI  - Operative management options for symptomatic flexible adult acquired flatfoot
      deformity: a review.

PMID- 20049417
TI  - How do bacteria sense and respond to low temperature?
AB  - Rigidification of the membrane appears to be the primary signal perceived by a
      bacterium when exposed to low temperature. The perception and transduction of the
      signal then occurs through a two-component signal transduction pathway consisting
      of a membrane-associated sensor and a cytoplasmic response regulator and as a
      consequence a set of cold-regulated genes are activated. In addition, changes in
      DNA topology due to change in temperature may also trigger cold-responsive
      mechanisms. Inducible proteins thus accumulated repair the damage caused by cold
      stress. For example, the fluidity of the rigidified membrane is restored by
      altering the levels of saturated and unsaturated fatty acids, by altering the
      fatty acid chain length, by changing the proportion of cis to trans fatty acids
      and by changing the proportion of anteiso to iso fatty acids. Bacteria could also
      achieve membrane fluidity changes by altering the protein content of the membrane
      and by altering the levels of the type of carotenoids synthesized. Changes in RNA
      secondary structure, changes in translation and alteration in protein
      conformation could also act as temperature sensors. This review highlights the
      various strategies by which bacteria senses low temperature signal and as to how
      it responds to the change.

PMID- 20049418
TI  - Interaction of transcription activator GvpE with TATA-box-binding proteins of
      Halobacterium salinarum.
AB  - GvpE is the transcriptional activator of the gvp gene cluster involved in gas
      vesicle formation in Haloabacterium salinarum. A 20-nucleotide sequence is
      required for the GvpE-mediated activation of the two oppositely oriented gvp
      promoters, P ( A ) and P ( D ). This sequence is located adjacent to the TATA-box
      and the transcription factor-B-binding site BRE, suggesting an interaction
      between GvpE and proteins of the transcription initiation apparatus. Here, we
      analysed the interaction of GvpE with the five different TATA-box-binding
      proteins, TBP, of Hbt. salinarum PHH1. The His-tagged TbpA through TbpE proteins
      were produced in Escherichia coli, bound to Ni-NTA matrices and tested for
      interaction with GvpE by protein-protein affinity chromatography. All Tbp(His)
      proteins retained the two different GvpE proteins from lysates of Haloferax
      volcanii transformants expressing the respective gvpE reading frame in pJAS35.
      Also, both GvpE(His) proteins bound to Ni-NTA matrices retained TbpB, whereas the
      20-kDa soluble gas vesicle protein GvpH(His) neither bound TbpB nor GvpE from the
      respective lysates of Hfx. volcanii. From these results, it appears that GvpE
      interacts with any TBP of Hbt. salinarum. This interaction might attract TBP and
      subsequently TFB and RNAP to the promoter and thus enhance transcription of the
      gvp gene cluster.

PMID- 20049419
TI  - A comparative analysis of chromosomal aberrations in cultured human lymphocytes
      due to fluoroquinolone drugs at different expression periods.
AB  - Fluoroquinolones (FQ) are broad-spectrum antibacterial agents widely used for the
      treatment of infections with various types of gram negative and gram positive
      bacteria. Specifically, gatifloxacin (GFX) is under development as a component in
      a new antituberculosis fixed-dose drug combination. In the context of this
      project, GFX was also tested for genotoxic activity in human peripheral
      lymphocytes, and the induction of chromosomal aberrations by GFX in PHA-M
      stimulated cultured human lymphocytes, investigated under conditions of
      conventional and increased expression times, was further compared to the
      analogous effects induced by some other second- and third-generation FQ
      antibacterial agents, namely ofloxacin (OFX), ciprofloxacin (CFX) and
      sparfloxacin (SFX). OFX did not induce any significant chromosomal aberrations in
      human lymphocytes. CFX and SFX exhibited slight to moderate clastogenic potential
      at cytotoxic concentrations (150, 175, 200 and 225 microg/ml), and GFX, a third
      generation FQ, induced a clear, concentration-dependent increase in the frequency
      of chromosomal aberrations at cytotoxic concentrations (150, 200 and 250
      microg/ml). These effects were not apparent when metaphases were analysed at the
      conventionally used sampling time of 24 h, but only after prolongation of the
      expression time between treatment and harvesting to a sampling time of 36 h (4 h
      exposure and 32 h expression period). Also, an increased incidence of numerical
      aberrations (polyploidy and endoreduplication) was seen with GFX at non-cytotoxic
      concentrations (12.5, 25, 50 and 75 microg/ml). These effects can be attributed
      to the slight cross-reactivity of FQs between their inhibitory activity towards
      their intended targets, the prokaryotic type II topoisomerase enzymes DNA gyrase
      and topoisomerase IV, and the analogous mammalian enzyme topoisomerase II. We
      have also observed the formation of polycentrics, i.e., chromosomes with five to
      six centromeres, a rarely reported structural aberration, in GFX-treated cells.
      The significance of these observations with respect to the conventional conduct
      of such studies and to the interpretation of the effects is discussed.

PMID- 20049421
TI  - Segmental control for adaptive locomotor adjustments during obstacle clearance in
      healthy young adults.
AB  - Anticipatory locomotor adjustments (ALAs) are used during locomotion to perform
      tasks, such as obstacle clearance, although not much is known as to how these
      ALAs are implemented by the central nervous system (CNS). The current study
      applied the planar law of intersegmental coordination to both leading and
      trailing limbs in a paradigm in which obstacle height and depth were manipulated
      to propose how ALAs are controlled. Ten healthy young adults stepped over nine
      obstacle conditions. Full-body 3D kinematic data were collected and elevation
      angles of the foot, shank, and thigh in the sagittal plane were calculated. For
      each limb within each trial, a principal component analysis was applied to limb
      segment trajectories. As well, a Fourier harmonic series was used to represent
      segment elevation angle trajectories, and phase differences between adjacent
      segments were determined. Planarity was consistently high in both limbs for all
      obstacle conditions, although significant differences between obstacle heights
      were observed. Increases in covariance loop width and rotation of the covariance
      plane accompanied changes in planarity. As observed in previous studies,
      fundamental harmonic phase differences between adjacent segments were highly
      correlated to plane characteristics and these phase differences changed
      systematically with increases in obstacle height. From the results, it is
      proposed that if a given environment requires a change in locomotion, the CNS
      adjusts a basic locomotor pattern if needed through the manipulation of the phase
      differences in the fundamental harmonics of the elevation angles between adjacent
      segments and elevation angle amplitude (with a constraint being intersegmenal
      elevation angle planarity).

PMID- 20049422
TI  - Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis
      in patients with Parkinson's disease.
AB  - Parkinson's disease (PD) patients have been reported to have lower bone mineral
      density (BMD) and higher fracture risk than individuals without PD. We assessed
      the association between hyperhomocysteinemia due to levodopa intake and BMD in PD
      patients. We measured serum homocysteine (Hcy) concentrations and BMD in the
      proximal femur and lumbar spine of PD patients aged 55 years or older (n = 95)
      and three age-/gender-matched control subjects (n = 285). The prevalence of
      osteoporosis was higher in both men (2.5-fold) and women (1.7-fold) with PD than
      in controls, and adjusted odds ratios for osteoporosis were 3.57 (95% confidence
      interval [CI], 1.25-10.20) for men and 2.54 for women (95% CI, 1.31-4.93) with
      PD. Serum Hcy concentrations were significantly higher in PD patients (median =
      13.0 micromol/l) than controls (median = 11.5 micromol/l) (P = 0.005). Serum Hcy
      concentrations were independently associated with BMD values at all proximal
      femur sites in all subjects (P = 0.005 to 0.012). In PD patients, higher serum
      Hcy concentrations were independently associated with higher fracture risk (P =
      0.029). PD patients taking higher doses of levodopa had significantly higher
      serum Hcy concentrations (P = 0.013), and greater levodopa intake was associated
      with lower BMD values in some areas (P = 0.008 to 0.029). In conclusion, these
      findings indicate that hyperhomocysteinemia due to levodopa intake may be one
      additional risk factor for osteoporosis and fracture in PD patients. Reducing Hcy
      may be a therapeutic modality for treating osteoporosis in PD patients taking
      levodopa.

PMID- 20049423
TI  - Stent-graft treatment of traumatic carotid artery dissecting pseudoaneurysm.
AB  - INTRODUCTION: Traumatic pseudoaneurysm of the internal carotid artery (ICA) is a
      rare but serious complication following blunt or penetrating trauma. These
      lesions are difficult to repair surgically. Endovascular management, including
      parent vessel occlusion, bare stent placement, and stent-assisted coil placement,
      are reported to be safe and effective but have certain disadvantages. Placement
      of covered stent grafts has been recently reported but without enough follow-up
      results to achieve consensus. METHODS: In this investigation, we present our
      experience with seven cases of traumatic ICA dissecting pseudoaneurysm treated
      with stent graft with follow-up between 1 and 33 months. RESULTS: Among the seven
      patients, one patient died due to septic shock 7 days after stenting. Follow-up
      angiography or Doppler ultrasound of the other six patients revealed optimal
      result with occluded pseudoaneurysm without restenosis of the ICA. CONCLUSIONS:
      Our results suggest that placement of stent grafts is a safe and effective method
      for treating ICA traumatic-dissecting pseudoaneurysm.

PMID- 20049424
TI  - Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in
      multiple sclerosis.
AB  - INTRODUCTION: Cerebral atrophy is a compound measure of the neurodegenerative
      component of multiple sclerosis (MS) and a conceivable outcome measure for
      clinical trials monitoring the effect of neuroprotective agents. In this study,
      we evaluate the rate of cerebral atrophy in a 6-month period, investigate the
      predictive and explanatory value of other magnetic resonance imaging (MRI)
      measures in relation to cerebral atrophy, and determine sample sizes for future
      short-term clinical trials using cerebral atrophy as primary outcome measure.
      METHODS: One hundred thirty-five relapsing-remitting multiple sclerosis patients
      underwent six monthly MRI scans from which the percentage brain volume change
      (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2
      lesions, and persistent black holes (PBH) were determined. By means of multiple
      linear regression analysis, the relationship between focal MRI variables and PBVC
      was assessed. Sample size calculations were performed for all patients and
      subgroups selected for enhancement or a high T2 lesion load at baseline. RESULTS:
      A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p <
      0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing
      lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were
      associated with an increased rate of atrophy. For a 50% decrease in rate of
      atrophy, the sample size calculations showed that approximately 283 patients per
      arm are required in an unselected sampled population and 185 patients per arm are
      required in a selected population. CONCLUSION: Within a 6-month period,
      significant atrophy can be detected and on-study associations of PBVC and PBHs
      emphasizes axonal loss to be a driving mechanism. Application as primary outcome
      measure in short-term clinical trials with feasible sample size requires a potent
      drug to obtain sufficient power.

PMID- 20049425
TI  - Comparative genomic and phylogenetic analyses reveal the evolution of the core
      two-component signal transduction systems in enterobacteria.
AB  - The two-component signal transduction system (TCST) consists of a histidine
      kinase (HK) and a response regulator (RR). TCSTs play important roles in sensing
      and reacting to environmental changes, and in bacterial pathogenesis. Previously,
      we have identified and characterized TCSTs in Erwinia amylovora, a severe plant
      enterobacterial pathogen, at genome-wide level. Here we conducted a comparative
      genomic analysis of TCSTs in 53 genomes of 16 enterobacterial species. These
      species include important plant, animal, human, and insect pathogenic,
      saprophytic or symbiotic microorganisms. Comparative genomic analysis revealed
      that enterobacteria contain eight pairs of core TCSTs. Phylogenetic trees
      reconstructed from a concatenation of the core set of TCSTs from enterobacteria
      and for individual TCST proteins from species in Proteobacteria showed that most
      TCST protein trees in the Enterobacteriaceae or in species of the gamma
      Proteobacteria agreed well with that of the corresponding 16S rRNA gene. It also
      showed that co-evolutionary relationships existed between cognate partners of the
      HKs and RRs. Several core TCSTs were quite ancient and universal based on
      phylogenomic analysis of protein structures. These results indicate that the core
      TCSTs are relatively conserved, and suggest that these enterobacteria may have
      maintained their ancient core TCSTs and might acquire specific new TCSTs for
      their survival in different environments or hosts, or may have evolved new
      functionalities of the core TCSTs for adaptation to different ecological niches.

PMID- 20049426
TI  - Novel transatrial septoplasty technique for neonates with hypoplastic left heart
      syndrome and an intact or highly restrictive atrial septum.
AB  - Two patients born with hypoplastic left heart syndrome and an intact or highly
      restrictive atrial septum requiring emergent intervention are presented. For both
      patients, rapid septoplasty was performed using a hybrid approach involving
      direct atrial puncture and transatrial cutting balloon dilation of the atrial
      septum. This technique facilitates safe and rapid procedural completion and
      minimizes the risk of procedural complications in this very-high-risk patient
      population.

PMID- 20049427
TI  - Anatomically corrected malposition of the great arteries.
AB  - We present cardiac magnetic resonance images of a 6-year-old with a suspected
      great artery abnormality in the setting of mesocardia, atrial situs solitus, D
      looping of the ventricles, and anatomically corrected malposition of the great
      arteries with subaortic and subpulmonary conus.

PMID- 20049428
TI  - MHC class II DRB1 gene polymorphism in the pathogenesis of Maedi-Visna and
      pulmonary adenocarcinoma viral diseases in sheep.
AB  - Ovine pulmonary adenocarcinoma (OPA) and Maedi-Visna (Maedi) are two chronic
      respiratory diseases of retroviral origin which occur worldwide. It is known that
      different host genetic factors influence the outcome of viral infections. To
      determine if variation in the Mhc-DRB1 gene was associated with progression to
      these ovine diseases, sheep lungs with and without OPA and Maedi lesions were
      collected. A sequence-based method was applied and 40 different alleles were
      detected in the sample analysed. In the allele-by-allele association analysis,
      allele DRB1*0325 had a significant association with susceptibility to Maedi (P =
      0.045). For OPA, DRB1*0143 and DRB1*0323 were significantly associated with
      susceptibility (P = 0.024 and P = 0.029), and allele DRB1*0702 was significantly
      associated with resistance (P = 0.012). Based on these results, the Mhc-DRB1
      alleles were classified by effect in three categories-susceptible (S), resistant
      (R) and neutral (N)-and animals were reassigned the genotypes as S/S, S/R, S/N,
      R/R, R/N and N/N. In a second analysis, penalised logistic regression models
      including a flock effect were run. In Maedi, significant association was detected
      for the N/S heterozygote (P = 0.0007), but not for the S/S homozygote, probably
      as a result of the low number of S/S animals. In OPA, association was detected
      for both the S/S and R/R homozygotes (P = 0.005 and P = 0.047). This allele
      grouping method may be applied in association studies with highly variable genes.
      This is the first study demonstrating significant associations between sheep Mhc
      DRB1 alleles and susceptibility to OPA and Maedi. Therefore, both diseases are
      suitable candidates for more comprehensive genetic studies.

PMID- 20049429
TI  - Improved production of the tallysomycin H-1 in Streptoalloteichus hindustanus
      SB8005 strain by fermentation optimization.
AB  - Tallysomycin (TLM) H-1, a novel TLM analog, is the major product isolated from
      Streptoalloteichus hindustanus SB8005, a genetically engineered strain from S.
      hindustanus E465-94 ATCC 31158. Based on the structural comparison and
      experimental assays, TLM H-1 represents a novel bleomycin (BLM) analog displaying
      DNA cleavage activity similar to its parent compounds TLM and BLM, both
      representatives of the glycopeptide anticancer antibiotics. The low titer of TLM
      H-1 in the engineered SB8005 strain has greatly limited its further study. In
      this paper, fermentation optimization for TLM H-1 production in the SB8005 strain
      is described; single-factor optimization and response surface methodology proved
      invaluable. The results indicated that three variables including distiller's
      grains and solubles, copper sulfate, and maltose out of eight parameters could
      significantly influence the TLM H-1 production. With systematic comparison and
      evaluation, the final optimized fermentation medium was determined. The optimized
      yield of TLM H-1 in the bench-top fermentor was 249.9 mg/L, which is 26.8 times
      higher than reported using the original medium, and 12.9-fold higher than that of
      the parent compound TLM produced by the wild-type strain. This work provides
      important parameters for TLM H-1 production by fermentation and should facilitate
      further mechanistic studies and clinical developments of TLM H-1 as an anticancer
      agent.

PMID- 20049430
TI  - Usefulness of percutaneous biopsy in diagnosing benign renal masses that mimic
      malignancy.
AB  - Percutaneous biopsy has long been used to diagnose malignancies of the kidney. It
      is an established technique with multiple indications. Percutaneous biopsy now
      can be used to diagnose benign conditions that may mimic a malignancy and lead to
      unnecessary treatments. Advances in cytological techniques such as
      immunocytochemistry and cytogenetics have allowed for an increased diagnostic
      yield. In this review, various benign entities that may present as a renal mass
      are discussed and the vital role of percutaneous biopsy detailed.

PMID- 20049431
TI  - Regulation of immunity and oncogenesis by the IRF transcription factor family.
AB  - Nine interferon regulatory factors (IRFs) compose a family of transcription
      factors in mammals. Although this family was originally identified in the context
      of the type I interferon system, subsequent studies have revealed much broader
      functions performed by IRF members in host defense. In this review, we provide an
      update on the current knowledge of their roles in immune responses, immune cell
      development, and regulation of oncogenesis.

PMID- 20049433
TI  - T-tube duodenocholangiostomy for the management of duodenal fistulae.
AB  - BACKGROUND: The tube decompression of the duodenum through an additional point of
      access of the duodenal wall or occasionally via the leak site decreases morbidity
      and mortality in patients with duodenal fistula. The objective of this paper is
      to present the detailed technique and clinical benefits of simplified duodenal
      and biliary decompression achieved by transampullary insertion of a T-tube with
      one-step duodenal closure for the prevention and/or treatment of duodenal leak.
      METHODS: The duodenocholangiostomy using T-tube with laterally perforated long
      duodenal limb was performed preventively in 4 patients and as a secondary
      procedure for septic duodenal leak in another selected 12. The mean output from
      the fistula, length of hospital stay, incidence of pancreatitis, as well as any
      postoperative septic events was recorded. The nutritional schedule during the in
      early postoperative period also was analyzed. RESULTS: The outcome was favorable
      for all patients. The mean length of hospital stay was 19 days. Septic events,
      such as wound or urinary tract infections, were observed in 30% of patients.
      Serum amylase and lipase activity was increased in two patients without a
      clinical picture of pancreatitis. Mean volume of T-tube duodenocholangiostomy
      drainage was approximately 500 ml per day during the first postoperative week.
      Enteral feeding was commenced 10-52 (mean, 21) hours after surgery and was
      followed by the initiation of normal diet on average 5 days postoperatively.
      CONCLUSIONS: Duodenocholangiostomy performed for duodenal decompression may be a
      promising alternative to classical tube duodenostomy for selected patients;
      however, further studies should be made to evaluate fully its practical value.

PMID- 20049432
TI  - Peritoneal damage: the inflammatory response and clinical implications of the
      neuro-immuno-humoral axis.
AB  - BACKGROUND: The peritoneum is a bilayer serous membrane that lines the abdominal
      cavity. We present a review of peritoneal structure and physiology, with a focus
      on the peritoneal inflammatory response to surgical injury and its clinical
      implications. METHODS: We conducted a nonsystematic clinical review. A search of
      the Ovid MEDLINE database from 1950 through January 2009 was performed using the
      following search terms: peritoneum, adhesions, cytokine, inflammation, and
      surgery. RESULTS: The peritoneum is a metabolically active organ, responding to
      insult through a complex array of immunologic and inflammatory cascades. This
      response increases with the duration and extent of injury and is central to the
      concept of surgical stress, manifesting via a combination of systemic effects,
      and local neural pathways via the neuro-immuno-humoral axis. There may be a
      decreased systemic inflammatory response after minimally invasive surgery;
      however, it is unclear whether this is due to a reduced local peritoneal
      reaction. CONCLUSIONS: Interventions that dampen the peritoneal response and/or
      block the neuro-immuno-humoral pathway should be further investigated as possible
      avenues of enhancing recovery after surgery, and reducing postoperative
      complications.

PMID- 20049434
TI  - Peritoneal infusion with cold saline decreased postoperative intra-abdominal
      adhesion formation.
AB  - BACKGROUND: Postoperative intra-abdominal adhesion is a common morbidity after
      laparotomy. We try to determine whether peritoneal infusion with cold saline may
      decrease postoperative intra-abdominal adhesion formation. METHODS: Ninety-six
      male BALB/c mice weighing 25-30 g were randomized into four groups: (I) adhesion
      model with infusion of 4 degrees C cold saline, (II) adhesion model with infusion
      of room temperature saline, (III) adhesion model without infusion of saline, and
      (IV) sham operation without infusion of saline. Adhesion scores, incidence of
      adhesion, and serum cytokines were measured at postoperative days 1, 3, 7, and
      14. RESULTS: Group I had lower adhesion scores than groups II and III (P <
      0.0001). IL-6, IL-10, and TNF-alpha were significantly increased in the groups I,
      II, and III compared to group IV (P < 0.0001). IL-6 in group I was significantly
      decreased compared to that in group III (P < 0.0004). IL-10 in group I was
      significantly increased compared to that in groups II (P < 0.0001) and III (P <
      0.05). TNF-alpha in group I was significantly decreased compared to that in
      groups II (P < 0.0004), and III (P < 0.05). CONCLUSION: Peritoneal infusion with
      cold saline may decrease the degree of postoperative intra-abdominal adhesion
      formation.

PMID- 20049435
TI  - C-reactive protein is an early predictor of septic complications after elective
      colorectal surgery.
AB  - BACKGROUND: Nowadays, most patients who undergo colorectal surgery are discharged
      early. An early predictor of septic complications could avoid readmissions and
      decrease morbidity. CRP could be a good predictor allowing a safe discharge.
      METHODS: A prospective, observational study was conducted from November 2007 to
      October 2008. All patients who underwent elective colorectal surgery were
      included. Clinical (temperature, pulse, abdominal tenderness, bowel movements)
      and laboratory data (C-reactive protein, leukocyte count) were recorded and
      evaluated as early predictors of septic complications (namely, anastomotic
      leaks). All detected leaks were considered fistulas, independently of their
      clinical significance. Clinical and inflammatory parameters were analyzed with
      univariate and multivariate techniques; logistic regression was performed and
      areas under the receiver operating characteristic curve were compared. RESULTS: A
      total of 133 patients were included. The overall incidence of anastomotic leaks
      was 15.5% and mortality was 4.5%. C-reactive protein at postoperative days 2 and
      4 was a good predictor of anastomotic leak (areas under the curve were 0.715 and
      0.845, respectively) and other postoperative septic complications (areas under
      the curve were 0.804 and 0.787), showing the highest accuracy among clinical and
      laboratory data. A cutoff of 125 mg/l in the level of C-reactive protein at
      postoperative day 4 yielded a sensitivity of 81.8% and a negative predictive
      value of 95.8% for the detection of anastomotic leakage. CONCLUSIONS: C-reactive
      protein is a simple way to ensure a safe discharge from hospital after elective
      colorectal surgery. Patients with CRP values >125 mg/l on the fourth
      postoperative day should not be discharged.

PMID- 20049436
TI  - A time-saving technique for specimen extraction in sleeve gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG), first intended as the first
      step of biliopancreatic diversion with duodenal switch (BPD-DS), is gaining
      popularity as a per-se procedure because of its effectiveness on weight loss and
      comorbidity resolution. The extraction of the gastrectomy specimen could be
      challenging and time-consuming. Different techniques have been described for
      specimen withdrawal. In this article we report the technique adopted in more than
      250 LSGs performed in our department. METHODS: In the first 90 LSGs performed in
      our department from October 2002, the specimen was extracted in a retrieval bag
      using an endoloop. In the following 160 cases the technique has been simplified:
      the grasped specimen is withdrawn through the 15-mm trocar site without any
      additional device. RESULTS: We registered only two cases of wound infection
      (1.2%) with the simplified technique, both occurring in the initial cases. There
      were no cases of trocar site hernia formation. CONCLUSION: The technique
      described does not require any special devices and seems to be simpler, saves
      time, and is cost effective if compared with other techniques previously
      reported.

PMID- 20049437
TI  - A systematic review of cases reporting needle tract seeding following thyroid
      fine needle biopsy.
AB  - BACKGROUND: Because of its accuracy and cost-effectiveness, thyroid fine needle
      biopsy (FNB) is the procedure of choice in the preoperative management of thyroid
      nodules. Needle tract seeding (NTS) has been a concern since the earliest days of
      FNB, contributing to the delayed acceptance of FNB as a safe procedure. In this
      review we tried to systematically record all reports of NTS after diagnostic
      thyroid FNB and provide useful hints to minimize the risk of NTS. METHODS:
      Computerized advanced search for primary evidence was performed in the PubMed
      (Public/Publisher Medline) electronic database. The search was not limited by
      publication time or English language. RESULTS: Ten relevant articles were found:
      eight case reports, one case in a surgical series, and one retrospective
      observational study. CONCLUSIONS: Despite initial concerns about the risk of NTS,
      FNB is now considered to be a safe procedure. Although proper FNB technique can
      reduce its risk, NTS is an unavoidable complication of FNB, which clinicians
      should be aware of. However, the incidence of NTS is low and it doesn't seem to
      affect the prognosis because the seedings can be surgically removed without
      recurrence. The management of the thyroid nodules is to-date based on FNB, and
      the benefits from FNB (elimination of needless imaging and surgery) far outweigh
      the potential risk for NTS.

PMID- 20049438
TI  - Role of collaborative academic partnerships in surgical training, education, and
      provision.
AB  - The global disparities in both surgical disease burden and access to delivery of
      surgical care are gaining prominence in the medical literature and media.
      Concurrently, there is an unprecedented groundswell in idealism and interest in
      global health among North American medical students and trainees in anesthesia
      and surgical disciplines. Many academic medical centers (AMCs) are seeking to
      respond by creating partnerships with teaching hospitals overseas. In this
      article we describe six such partnerships, as follows: (1) University of
      California San Francisco (UCSF) with the Bellagio Essential Surgery Group; (2)
      USCF with Makerere University, Uganda; (3) Vanderbilt with Baptist Medical
      Center, Ogbomoso, Nigeria; (4) Vanderbilt with Kijabe Hospital, Kenya; (5)
      University of Toronto, Hospital for Sick Children with the Ministry of Health in
      Botswana; and (6) Harvard (Brigham and Women's Hospital and Children's Hospital
      Boston) with Partners in Health in Haiti and Rwanda. Reflection on these
      experiences offers valuable lessons, and we make recommendations of critical
      components leading to success. These include the importance of relationships,
      emphasis on mutual learning, the need for "champions," affirming that local
      training needs to supersede expatriate training needs, the value of collaboration
      in research, adapting the mission to locally expressed needs, the need for a
      multidisciplinary approach, and the need to measure outcomes. We conclude that
      this is an era of cautious optimism and that AMCs have a critical opportunity to
      both shape future leaders in global surgery and address the current global
      disparities.

PMID- 20049439
TI  - Complications analysis with postoperative choledochoscopy for residual bile duct
      stones.
AB  - BACKGROUND: This study was designed to review the experience of this department
      with the treatment of post-common bile duct exploration residual stones using
      choledochoscopy and to analyze the complications of choledochoscopy and explore
      effective methods of prevention. METHODS: A choledochoscope (PENTAX
      fibercholedochoscope and electronic choledochoscope PENTAX ECN-1530) was used. A
      total of 2,882 postoperative percutaneous choledochoscopy (POC) sessions were
      performed on 986 patients with residual bile duct stones from 1980 to 2008 (408
      men, 578 women; ages range, 21-82 years). Forty-five of these had undergone
      laparoscopic common bile duct exploration (LCBDE); the rest had open bile duct
      exploration. Seventy-six participants had choledochoscopy examination (for
      diagnosis only), and in 910 patients it was performed for both diagnosis and
      therapy (calculi extraction). In 68 cases, plasma shock wave lithotripsy (PSWL)
      was performed for larger stones before choledochoscopy extraction. RESULTS: The
      mean duration of choledochoscopy was 25 min (range, 10 min to 2 h), with a mean
      frequency of 2.85 times (range, 1-11). No mortalities occurred. The procedure was
      unsuccessful in 28 cases in which stones were not accessible because they were
      embedded in distal hepatic ducts or because they were in proximal ducts that were
      severely stenosed. Complications resulted in 13 cases and included perforated
      sinus, biliary peritonitis, sinus hypoplasia, destruction of the T-tube system
      leading to obstruction, basket incarceration, bleeding, and intestinal fistular.
      Choledochoscopic stone clearance was achieved in 95.5% of the cases. CONCLUSIONS:
      Choledochoscopy is an important treatment option for hepatolithus. It has a high
      efficiency for stone extraction and fewer complications. However, it should be
      noted that some of its complications are potentially life-threatening.

PMID- 20049440
TI  - An algorithm informed by the parathyroid hormone level reduces hypocalcemic
      complications of thyroidectomy.
AB  - BACKGROUND: Measurement of the parathyroid hormone (PTH) level following total
      thyroidectomy (TTx) may allow prediction of postoperative hypocalcemia. We
      present an algorithmic method of managing hypocalcemia pre-emptively, based on
      the PTH level 1 h after operation. MATERIALS AND METHODS: We examined 423
      consecutive patients undergoing TTx at a single institution. A subset of patients
      were managed using an algorithm involving routine postoperative oral calcium
      administration and the early addition of oral calcitriol in patients with a low 1
      h postoperative PTH level. Algorithm patients were compared to a concurrent,
      conventionally managed group. Outcomes measured included serum calcium levels,
      symptoms of hypocalcemia, postoperative complications, and receipt of intravenous
      (i.v.) calcium. RESULTS: The algorithm was applied in 135 patients, and 288
      patients were managed conventionally. Critically low calcium levels (total
      calcium <7.5 mg/dl [1.88 mmol/l] or ionized calcium <0.94 mmol/l) were less
      common in algorithm patients (10.6% vs. 25.3%; p < 0.005). Much of this
      difference was attributable to the protective impact of the algorithm on patients
      undergoing TTx for cancer, 30% of whom developed critically low calcium levels
      when managed conventionally. Among patients requiring i.v. calcium, algorithm
      patients received fewer doses (1.29 vs. 1.86; p < 0.05). Low 1-h PTH levels were
      found in 21% (28/133) of algorithm patients, but these did not correlate with low
      calcium levels, suggesting that the algorithm compensated adequately for
      temporary hypoparathyroidism. No patients developed hypercalcemia. CONCLUSIONS:
      An algorithmic approach incorporating early postoperative PTH levels and routine
      administration of oral calcium reduces the risk of severe hypocalcemia after
      total thyroidectomy.

PMID- 20049441
TI  - Standard outpatient re-evaluation for patients not admitted to the hospital after
      emergency department evaluation for acute abdominal pain.
AB  - BACKGROUND: The aim of the present study was to investigate the efficacy and
      safety of standard outpatient re-evaluation for patients who are not admitted to
      the hospital after emergency department surgical consultation for acute abdominal
      pain. METHODS: All patients seen at the emergency department between June 2005
      and July 2006 for acute abdominal pain were included in a prospective study using
      a structured diagnosis and management flowchart. Patients not admitted to the
      hospital were given appointments for re-evaluation at the outpatient clinic
      within 24 h. All clinical parameters, radiological results, diagnostic
      considerations, and management proposals were scored prospectively. RESULTS: Five
      hundred patients were included in this analysis. For 148 patients (30%), the
      final diagnosis was different from the diagnosis after initial evaluation. Eighty
      five patients (17%) had a change in management after re-evaluation, and 20 of
      them (4%) were admitted to the hospital for an operation. Only 6 patients (1.2%)
      had a delay in diagnosis and treatment, which did not cause extra morbidity.
      CONCLUSIONS: Standard outpatient re-evaluation is a safe and effective means of
      improving diagnostic accuracy and helps to adapt management for patients that are
      not admitted to the hospital after surgical consultation for acute abdominal pain
      at the emergency department.

PMID- 20049442
TI  - Assessment of clopidogrel non-response by the PFA-100 system using the new test
      cartridge INNOVANCE PFA P2Y.
AB  - Until now, the PFA-100 system has been considered unsuitable for monitoring
      clopidogrel efficacy. The authors evaluated platelet function in peripheral
      arterial occlusive disease (PAOD) patients using a new PFA-100(R) test cartridge
      (product name: INNOVANCE PFA P2Y*) specifically designed for this purpose. Twenty
      two stable PAOD patients on antithrombotic therapy with clopidogrel alone (n =
      22) and 18 patients undergoing a peripheral catheter intervention, preliminarily
      treated with 100 mg/day of aspirin followed by co-administration of clopidogrel
      (loading dose 300 mg, maintenance dose 75 mg/day), were enrolled in this study.
      Defining non-responsiveness to clopidogrel as an aggregation response within the
      reference range (90% central interval), four (18.2%) non-responders using light
      transmittance aggregometry (LTA) induced by 5 microM adenosine diphosphate (ADP)
      and six (27.3%) non-responders using LTA induced by 2 microM ADP (LateAggr >72.1%
      and >42.9%, respectively) were identified. INNOVANCE PFA P2Y* determined six
      (27.3%) non-responders (CT < 87 s). Agreement between the two aggregometry assays
      and INNOVANCE PFA P2Y* on the definition of clopidogrel response and non-response
      exceeded 70%. Only three patients were uniformly identified as clopidogrel non
      responders by all three assays. When clopidogrel was co-administered with
      aspirin, two (11.1%) non-responders to clopidogrel were detected with INNOVANCE
      PFA P2Y*, whereas ADP-induced LTA found all patients to be responsive. INNOVANCE
      PFA P2Y* appears to be suitable for monitoring the effect of clopidogrel on
      platelet function. Its sensitivity in detecting responsiveness or non
      responsiveness to clopidogrel is comparable to ADP-induced LTA. Additional
      prospective studies are needed to clarify the clinical relevance of the test
      results and classification obtained with INNOVANCE PFA P2Y*.

PMID- 20049443
TI  - Pharmacokinetics of sunitinib malate in subjects with hepatic impairment.
AB  - This study evaluated the effect of hepatic impairment on the pharmacokinetics of
      sunitinib and its active metabolite, SU12662. This open-label study enrolled
      subjects with normal hepatic function (n = 8), mild (Child-Pugh [CP]-A; n = 8),
      or moderate (CP-B; n = 8) hepatic impairment. Subjects received sunitinib 50 mg
      as a single oral dose. Mild or moderate hepatic impairment did not significantly
      alter sunitinib, SU12662, or total drug (TD) systemic exposure. In subjects with
      normal hepatic function, mild, or moderate hepatic impairment, respectively, TD
      AUC(0-infinity) was 1,938, 2,002, and 1,999 ng h/ml, TD AUC(0-last) was 1,913,
      1,956, and 1,958 ng h/ml, and TD C (max) was 26.0, 27.3, and 26.7 ng/ml. There
      were no other notable pharmacokinetic differences and sunitinib was well
      tolerated. The pharmacokinetic findings of this study do not indicate a need to
      adjust the currently approved starting dose of sunitinib (50 mg daily on Schedule
      4/2) for cancer patients with mild to moderate liver impairment.

PMID- 20049444
TI  - Multiple organ tuberculosis of lung, pleura, and peritoneum in ankylosing
      spondylitis during adalimumab therapy.
AB  - A case of multiple organ tuberculosis (TBc) involving lung, pleura, and
      peritoneum in a 39-year-old man with long-standing ankylosing spondylitis (AS)
      treated with adalimumab was presented. The relationship between antitumor
      necrosis factor-alpha (anti-TNF-alpha) therapy and TBc was also reviewed. This
      case illustrates that TBc can develop in multiple organs during adalimumab
      therapy, and thus, the awareness of serious complications of multiple organs and
      atypical extrapulmonary pattern of TBc during anti-TNF-alpha therapy needs to be
      increased.

PMID- 20049445
TI  - Responsiveness to intravenous immunoglobulins and occurrence of coronary artery
      abnormalities in a single-center cohort of Italian patients with Kawasaki
      syndrome.
AB  - Clues to predict the response to intravenous immunoglobulins (IVIG) and the
      development of coronary artery abnormalities (CAA) in children with Kawasaki
      syndrome (KS) are still undefined. We examined retrospectively the medical charts
      of children hospitalized between February 1990 and April 2009 with diagnosis of
      KS. A total of 32 Italian patients with a mean age of 23.8 months were analyzed
      and all received IVIG according to two schemes: 0.4 g/(kg day) for 5 days or 2
      g/kg in a single infusion, combined with oral acetylsalicylic acid. General,
      clinical and laboratory data were registered. Each patient was evaluated with
      echocardiography at admission, then with 3-day and weekly frequency,
      respectively, during hospital stay and for the first 6-8 weeks since onset, and
      finally with a regular 6-12 month follow-up over time, according to patient risk
      stratification. Five patients showing significantly higher values of C-reactive
      protein (CRP) at admission were IVIG-resistant after the first infusion (P =
      0.04) in comparison with the remaining 27. Five patients out of 32 developed CAA,
      with no statistical significance when analyzed for IVIG dosage or IVIG
      resistance. The demonstration of CAA was significantly higher in children aged
      <12 months (P = 0.037). Our experience, limited to a single-center cohort of 32
      patients with KS, though treated with two different IVIG schemes, has shown that
      higher values of CRP and younger age at onset are nodal points in determining,
      respectively, a failure in the response to IVIG and an increased occurrence of
      CAA.

PMID- 20049446
TI  - Comparison of the second and third generation anti-cyclic citrullinated peptide
      antibody assays in the diagnosis of Japanese patients with rheumatoid arthritis.
AB  - The anti-cyclic citrullinated peptide (CCP) antibody has become increasingly
      important in the diagnosis of rheumatoid arthritis (RA), especially for early
      diagnosis. The purpose of this study is to compare the diagnostic usefulness of
      the second and third generation anti-CCP antibody kits among Japanese patients
      with RA. Anti-CCP antibody titers were measured with the second generation
      (MESACUP CCP test, Medical and biological laboratories) and third generation
      (QUANTA Lite CCP3 IgG ELISA, Inova Diagnostics) kits using serum samples from 106
      rheumatoid arthritis (RA) patients and 57 non-RA patients. Sensitivities and
      specificities were compared. The sensitivity and specificity of the second
      generation anti-CCP (anti-CCP2) kit were 88.7 and 89.5%, and those of the third
      generation anti-CCP (anti-CCP3) kit were 91.5 and 87.7%. Area under the receiver
      operating curve showed that anti-CCP2 and anti-CCP3 had similar diagnostic
      performances. Diagnostic performance of the anti-CCP3 assay was comparable with
      the anti-CCP2 assay in Japanese patients with RA.

PMID- 20049447
TI  - Sonozaki syndrome: case report and review of literature.
AB  - Sonozaki syndrome--pustulotic arthro-osteitis (PAO) is a relatively rare, chronic
      illness. This disease belongs to the group of psoriatic arthritis (psoriasis
      arthropatica, artropatia psoriatica) which in turn belongs to the group of
      seronegative arthritis. Sonozaki syndrome includes palmoplantar pustulosis, PPP
      as well as arthro-osteitis. Clinically, symmetrically localised pustulae are
      observed on feet and hands. Effected joints are painful, swollen with a visible
      inflammation. Here, we describe a case of a woman aged 55 with a diagnosis of
      Sonozaki syndrome and hyperthyroidism. At the moment of admission multiple
      changes in the form of pustulae were observed on hands and soles, filled with pus
      and blood of the erythemal basis. Oral and genital mucosa were free from changes.
      The oedema within clavicle and sternum joints was without features of the severe
      inflammation and tactical tenderness. In additional tests, increased BSR 36/62
      was found. Bone scintigraphy-focuses of increased accumulation of MDP-Tc-99 m
      were found in the sternal projection of the clavicle ends at both sides, and the
      left-side change is bigger and more strongly saturated and can probably progress
      to the sternum's manubrium. As a result of the used treatment during
      hospitalisation, (cyclosporine 3 mg/kg and steroid external therapy upon the skin
      changes) the improvement of the local changes was observed as well as no
      progression in the joints' changes. At the moment, the patient is treated in the
      dermatological and rheumatological out-clinic. Early and correct diagnostics
      allows for efficient treatment of Sonozaki syndrome and decreases the risk of
      potential complications, such as the described systemic amyloidosis.

PMID- 20049448
TI  - Health-related quality of life and its associations with mood condition in
      familial Mediterranean fever patients.
AB  - The aim of the present study was to investigate the health-related quality of
      life (HRQOL) and mood conditions in familial Mediterranean fever (FMF) patients.
      Ninety FMF patients (F/M 60/30, median age 29) and 67 control subjects (F/M
      46/21, median age 30) were included in this study. HRQOL was assessed with short
      form-36 (SF-36) and mood conditions were assessed with hospital anxiety
      depression scale (HADS). FMF patients had significantly lower mean scores on SF
      36 physical components compared to the control group. However, mental components
      were comparable between groups. FMF patients were significantly more likely to
      have depression and anxiety compared to the control group [30 (33%) vs. 8 (12%),
      respectively, chi (2) = 9.58, OR (95% CI) = 3.7 (1.5-8.7), p < 0.01 for
      depression and 48 (53%) and 11 (16%), respectively, chi (2) = 22.31, OR (95% CI)
      = 5.8 (2.7-12.5), p < 0.001 for anxiety]. When frequency of anxious subjects was
      adjusted for the presence of concomitant depressive status as a confounding
      factor, the difference between the groups remained statistically significant [chi
      (2) = 11.86, OR (95% CI) = 5.4 (2.1-13.7), p < 0.01]. However, the difference of
      depression status between groups was not statistically significant when adjusted
      for the presence of concomitant anxiety status [chi (2) = 0.08, OR (95% CI) = 1.3
      (0.5-3.8), p = 0.78] and FMF was found to be independently associated with only
      anxiety [OR (95% CI) = 7.1 (2.3-20.3)]. In addition, pure anxious FMF subgroup
      had significantly lower scores of mental health and mental component summary when
      compared to normal mood subgroup. In conclusion, FMF might adversely affect
      HRQOL. Depression and anxiety are more frequent in FMF patients than healthy
      subjects.

PMID- 20049449
TI  - Evaluation of inflammatory change and bone erosion using a murine type II
      collagen-induced arthritis model.
AB  - The exact mechanism of rheumatoid arthritis (RA) is unclear, but a combination of
      genetic, environmental and hormonal factors is thought to be involved. This study
      examined the progressive arthritic reaction of murine type II collagen-induced
      arthritis (CIA), a representative animal model of RA. Arthritic reactions,
      including inflammation and bone erosion were examined using an objective non
      invasive method. Two scoring systems were used to evaluate changes in cutaneous
      inflammation and bone erosion during RA progression. The severity of inflammation
      was evaluated by visual scoring of erythema and edema, while the degree of bone
      erosion was quantified by macroradiographical erosion analysis of specific bones.
      A significant difference was observed in both visual (P = 0.0001, n = 7) and
      radiographic (P < 0.0001, n = 7) examinations for the RA group as compared to the
      control. The relationship between inflammatory change and erosive change in bone
      showed a significant positive correlation, r = 0.9550 (P < 0.0001, n = 7). The
      overall rate of asymmetry was 25.23% in both fore- and hindpaws. The results
      generated from these experiments show that murine CIA is a promising model for
      elucidating the mechanism of RA. In addition, the results of this study may be
      used for monitoring RA progression as well as screening therapy efficacy in the
      joint pathology.

PMID- 20049450
TI  - Perforin level in CD4+ T cells from patients with systemic lupus erythematosus.
AB  - CD4(+) T cells from patients with systemic lupus erythematosus (SLE) exhibit
      increased expression of various proteins contributing to defective function of
      CD4(+) T cells. We evaluated the transcript and protein levels of perforin (PRF1)
      in CD4(+) T cells from SLE patients (n = 41) and healthy individuals (n = 34).
      The CD4(+) T cells were obtained by a positive biomagnetic separation system. The
      amounts of mRNA were determined by reverse transcription and real-time
      quantitative PCR. The protein levels in the CD4(+) T cells were evaluated by
      Western blotting analysis. We observed significantly higher levels of PRF1
      protein (p = 0.013) in SLE CD4(+) T cells than in controls. There was no
      significant increase in PRF1 transcript levels (p = 0.908) in CD4(+) T cells from
      SLE patients as compared to healthy individuals. Moreover, we did not observe a
      correlation between PRF1 transcript and protein levels in SLE CD4(+) T cells and
      disease activity expressed by the SLEDAI scale. We confirmed previous
      observations that demonstrated higher levels of PRF1 protein in CD4(+) T cells
      from SLE patients. However, we did not find a correlation between PRF1
      transcripts and proteins in CD4(+) T cells and SLE disease activity.

PMID- 20049451
TI  - Quality of life in patients with ankylosing spondylitis: relationships with
      spinal mobility, disease activity and functional status.
AB  - The aim of this study was to evaluate quality of life (QOL) in patients with
      ankylosing spondylitis (AS) and to determine the relationships between QOL and
      clinical variables including spinal mobility, disease activity and functional
      status. Forty-eight adult patients who fulfilled the modified New York criteria
      for AS were included in the study. After detailed physical examination, disease
      specific instruments: the Bath ankylosing spondylitis disease activity index
      (BASDAI) and the Bath ankylosing spondylitis functional index (BASFI) were
      applied. QOL was assessed using short form-36 (SF-36). The mean age of the
      patients was 37.0 +/- 9.7 years and the mean duration of symptoms was 11.7 +/-
      8.4 years. Most affected domains of SF-36 were bodily pain, vitality, and
      physical role, respectively. No significant correlations were found between SF-36
      subgroup scores and chest expansion, wall-tragus distance, chin-sternum distance,
      and floor-finger tip distance. Only modified Schober correlated with two SF-36
      domains: physical role and bodily pain. BASDAI and BASFI scores had significant
      negative correlations with all SF-36 domains except for general health.
      Identification of QOL in patients with AS is very important in evaluation of
      illness-related sufferings and development of new management strategies.

PMID- 20049452
TI  - Role of sodium silicate in induction of scleroderma-related autoantibodies in
      brown Norway rats through oral and subcutaneous administration.
AB  - Silica hazard is a growing occupational problem and has been reported to be
      associated with scleroderma via case reports and occupational studies. The aim of
      this study is to demonstrate whether oral or subcutaneous silicate exposure can
      induce an autoimmunity and scleroderma susceptibility in immunosensitive rats.
      Sodium silicate in a dose of 3 mg in 0.2 ml NS was administered through oral and
      subcutaneous routes to 20 brown Norway rats. Autoantibodies including ANA, anti
      RNP, anti-SCL70 and anti-centromere were measured and compared with pre- and post
      challenge serum samples. Serum ANA and anti-RNP were high in significant number
      of rats (P < 0.05) of only the subcutaneous silicate group. There is an increase
      in the number of positive readings of autoantibodies at 14th week in comparison
      with the number of positive readings of autoantibodies at 7th week but P values
      were not significant. It may be concluded that silicate might induce autoimmunity
      and scleroderma and it seems to be that the longer the duration of exposure the
      greater the risk. This is probably the first experimental animal study
      demonstrating the induction of scleroderma-related autoantibodies after challenge
      with silicate.

PMID- 20049453
TI  - An infant with severe refractory Crohn's disease and homozygous MEFV mutation who
      dramatically responded to colchicine.
AB  - Previous studies have suggested that inflammatory bowel disease is particulary
      frequent and severe in familial Mediterranean fever (FMF) families. An 8-month
      old boy was admitted to our hospital with chronic bloody diarrhea, failure to
      thrive and high-grade fever. He was diagnosed as Crohn's disease (CD) based on
      clinical, laboratory and histological findings and, corticosteroid therapy was
      started. The patient did not respond to intensive medical therapy including
      intravenous corticosteroid, mesalazine, azathioprine, intravenous cyclosporine
      and enteral feeding. MEFV gene mutation analysis revealed homozygous M694V
      mutation. In addition to azathioprine and cyclosporine therapy, with the
      diagnosis of FMF, colchicine therapy was started and partial remission was
      observed within 2 weeks. To the best of our knowledge, this is the first report
      of association of CD and FMF in an infant. In cases of CD resistant to medical
      therapy, possibility of underlying FMF should be considered, especially in
      countries where FMF is prevalent.

PMID- 20049454
TI  - Use of cardiac MR imaging to evaluate the presence of myocarditis in autoimmune
      myositis: three cases.
AB  - Cardiac involvement in patients with idiopathic inflammatory myopathies
      (autoimmune myositis) is important to detect because it confers an increased risk
      of mortality. However, detection of myocardial involvement is hampered by a lack
      of sensitivity of traditional non-invasive methods, and the finding of elevated
      cardiac troponin T levels that may be due to regenerating skeletal muscle, rather
      than myocardial damage. Here, we describe three cases of inflammatory myositis
      with elevated troponin T levels, and non-specific echocardiographic and ECG
      findings. Cardiac MR imaging was useful in the evaluation for the presence of
      myocarditis or alternative cardiac pathology.

PMID- 20049455
TI  - Cochlear implantation in a bilateral sensorineural hearing loss patient with
      relapsing polychondritis.
AB  - Relapsing polychondritis (RP) is a rare disease which presents chondritis in
      multiple organs. Characteristic features include auricular chondritis, arthritis,
      nasal chondritis, ocular inflammation, respiratory tract involvement and
      audiovestibular damage. Fifty percent of cases of RP are associated with inner
      ear symptoms such as dizziness and hearing loss. We have recently encountered a
      case of RP in a 34-year-old man who had recurrent chondritis of both auricles and
      progressive bilateral profound sensorineural hearing loss; he had been treated
      many times with steroids, immunosuppressants, plasmapheresis treatments. We
      perfomed a successful cochlear implant surgery on the left ear of this patient.
      This raises the possibility of using cochlear implants in treating patients with
      immune-mediated inner ear disease as well as such RP patients.

PMID- 20049456
TI  - To clamp or not to clamp? Bladder management by suprapubic catheterization in
      patients with neurogenic bladder dysfunction.
AB  - PURPOSE: In a small subset of patients with neurogenic lower urinary tract
      dysfunction, insertion of suprapubic catheters (SPC) cannot be avoided. If SPC
      has to be utilized, catheter clamping and anticholinergic medication are often
      recommended, but evidence supporting this view is scarce. We determined the
      influence of anticholinergic medication and catheter clamping on urodynamic
      parameters and the status of the urinary tract in patients with chronic
      suprapubic catheterization. METHODS: In a retrospective study, the results of
      urodynamic testing, sonographic evaluations, and urinalyses of 85 patients with
      chronic (>1 year) suprapubic catheterization due to neurogenic bladder
      dysfunction were analyzed. RESULTS: The 51 male and 34 female patients (mean age
      55 years) were managed with an SPC for 65.3 +/- 48.0 months. Forty patients had
      an SPC for more than 60 months. Comparing the results before SPC insertion with
      the last follow-up examination, no significant differences in detrusor compliance
      and maximum detrusor pressure were detected, whereas bladder capacity
      significantly decreased. In three patients, alterations of the upper urinary
      tract were found. The results were not significantly different between the
      patients using anticholinergic medication and/or catheter clamping and those who
      did not. CONCLUSIONS: According to our study, routine use of anticholinergic
      medication and clamping of catheter does not seem to be necessary to preserve
      detrusor compliance and renal function in patients with SPC and neurogenic
      bladder dysfunction.

PMID- 20049457
TI  - The fate of conference abstracts: systematic review and meta-analysis of surgical
      treatments for men with benign prostatic enlargement.
AB  - OBJECTIVE: From the literature search for a government-commissioned systematic
      review on surgical treatments for benign prostatic enlargement (BPE), we
      identified the relevant conference abstracts of randomised controlled trials
      (RCTs) which failed to reach full publication and their data were not utilised.
      We aimed to ascertain, first, the reasons of failure to reach full publication
      and second, to estimate the impact of including the abstracts' data. DESIGN: A
      two-part study, consisting of a questionnaire survey and a sensitivity analysis
      of the above said review. METHODS: An ad hoc questionnaire was sent to each
      author of the relevant abstracts, as to determine the reasons of failure to reach
      full publication. The data from the abstracts were then extracted and
      incorporated into sensitivity analysis of the review. RESULTS: Forty-seven
      questionnaires were completed for 47 abstracts. Of these abstracts, 32 of them
      were claimed to have reached full publication. A number of reasons of failure to
      reach full publication were identified, for example: 'being written up' and 'lack
      of time'. Utilizable, relevant data were obtained from eight of the 47 abstracts,
      and put into sensitivity analysis. There were small changes in effect sizes and
      directions for three of 14 reviews' secondary outcomes. CONCLUSION: Common
      reasons of failure to reach full publication were also identified in the context
      for the BPE review. Inclusion of abstract data did not affect primary outcome
      defined in the original review. Identification, summarisation of conference
      abstracts and other grey literature should form an essential exercise for any
      systematic review.

PMID- 20049458
TI  - Effects of capture stress on free-ranging, reproductively active male Weddell
      seals.
AB  - Physiological stress responses to capture may be an indicator of welfare
      challenges induced by animal handling. Simultaneously, blood chemistry changes
      induced by stress responses may confound experimental design by interacting with
      the biological parameters being measured. Cortisol elevation is a common
      indicator of stress responses in mammals and reproductive condition can
      profoundly influence endocrine response. We measured changes in blood cortisol
      and testosterone induced by handling reproductively active male Weddell seals
      (Leptonychotes weddellii) early and late in the breeding season. Weddell seals
      have the highest resting cortisol levels of all mammals yet showed a clear,
      prolonged elevation in cortisol in response to capture. Responses were similar
      when first caught and when caught a second time, later in the breeding season.
      Baseline testosterone levels declined over the breeding season but were not
      altered by capture. Administering a light dose of diazepam significantly
      ameliorated the cortisol response of handled animals without affecting
      testosterone levels. This may be an effective way of reducing acute capture
      stress responses. Male breeding success in years males were handled was no
      different to the years they were not, despite the acute capture response,
      suggesting no long-term impact of handling on male reproductive output.

PMID- 20049459
TI  - Pollinating birds differ in spectral sensitivity.
AB  - Pollinating animals and their angiosperm hosts often show strong co-adaptation in
      traits that increase the likelihood of a successful transfer of pollen and
      nutrient rewards. One such adaptation is the reported colour difference caused by
      unequal distribution of anthocyanidin pigments amongst plant species visited by
      hummingbirds and passerines. This phenomenon has been suggested to reflect
      possible differences in the colour vision of these pollinating birds. The
      presence of any such difference in colour vision would arguably affect the
      ecological and evolutionary interactions between flowers and their visitors,
      accentuating differences in floral displays and attractiveness of plants to the
      favoured avian pollinators. We have tested for differences in colour vision, as
      indicated by the amino acid present at certain key positions in the short
      wavelength-sensitive type 1 (SWS1) visual pigment opsin, between the major groups
      of pollinating birds: the non-passerine Trochilidae (hummingbirds), the passerine
      Meliphagidae (honeyeaters) and Nectariniidae (sunbirds) plus five other Passerida
      passerine families. The results reveal gross spectral sensitivity differences
      between hummingbirds and honeyeaters, on the one hand, and the Passerida species,
      on the other.

PMID- 20049460
TI  - Diagnosis and treatment of vein of Galen aneurysmal malformations.
AB  - INTRODUCTION: Vein of Galen aneurysmal malformations (VGAM) are rare but
      clinically significant intracranial arteriovenous shunt lesions that most often
      present in neonates and infants. METHODS: Retrospective clinical data were
      collected for patients evaluated with a diagnosis of VGAM from 1994 to 2007.
      RESULTS: Thirteen patients with VGAM were evaluated from 1994 to 2007. Seven
      patients presented emergently with medically intractable cardiac failure, and six
      were treated in the first 2 weeks of life. Five children treated after this
      period (1.5-31 months of age) manifested enlarging head circumference, abnormal
      development, or subarachnoid hemorrhage. Eleven patients were managed
      endovascularly. Four disease or procedure-related complications occurred. Two
      complications were associated with poor outcome, both of which occurred in
      patients treated at less than 2 weeks of age. Two other patients experienced
      transient neurological deficits with no evidence of permanent sequelae. Outcome
      in the six patients treated emergently in the first 2 weeks of life included two
      patients who developed normally, one with mild to moderate neurological deficits,
      one with severe neurological deficits, and two deaths. Outcome in the five older
      patients (treated between 1.5 and 31 months) was considerably better than in the
      group treated early and included three with normal outcome and two with mild
      neurological deficits. CONCLUSIONS: Contemporary endovascular techniques remain
      the preferred treatment for VGAM in all age groups. Early diagnosis and
      multimodality treatment are essential for the best management and treatment of
      the complex constellation of clinical problems often arising from this disorder.

PMID- 20049461
TI  - Restrictive ventricular septal defect and critical subaortic stenosis in
      tetralogy of Fallot.
AB  - INTRODUCTION: Tetralogy of Fallot is characterized by a non-restrictive
      malalignment ventricular septal defect (VSD), an overriding aorta and right
      ventricular outflow tract obstruction resulting from anterior deviation of the
      infundibular septum. Due to the large VSD, systolic pressures are equal in both
      ventricles. In rare cases, redundant tricuspid valve tissue may prolapse into the
      VSD resulting in restriction of the defect size and causing suprasystemic
      pressure in the right ventricle. Subaortic obstruction by prolapse of the
      redundant tricuspid tissue into the left ventricular outflow tract, although
      theoretically possible in this situation, has not been described yet in the
      literature. CASE REPORT: We report on a newborn with tetralogy of Fallot
      presenting with cyanosis and severe arterial hypotension a few hours after birth.
      Echocardiography revealed redundant hammock-like accessory tricuspid valve tissue
      almost completely occluding the originally large VSD. Suprasystemic pressure in
      the right ventricle resulted in protrusion of tricuspid valve tissue across the
      VSD and thereby caused severe left ventricular outflow tract obstruction.
      Emergency pulmonary balloon valvuloplasty performed for decompression of the
      right ventricle, reduced prolapse of tricuspid tissue into the left ventricular
      outflow tract and resulted in significant improvement of pulmonary and systemic
      blood flow. CONCLUSION: In tetralogy of Fallot, accessory tricuspid valve tissue
      may obstruct the VSD as well as the left ventricular outflow tract resulting in a
      life threatening condition in newborns shortly after birth.

PMID- 20049462
TI  - Unusual cause of syncope in young girl: arrhythmogenic right ventricular
      cardiomyopathy.

PMID- 20049463
TI  - Glycoprotein VI as a prognostic biomarker for cardiovascular death in patients
      with symptomatic coronary artery disease.
AB  - BACKGROUND: Platelets play a critical role in arterial thrombosis, acute coronary
      syndrome (ACS) and stroke. Platelet collagen receptor glycoprotein VI (GPVI) is
      associated with acute coronary events and a poor clinical outcome. METHODS:
      Between January 2006 and March 2009, we evaluated 2,213 consecutive patients in a
      prospective study design, who presented with chest pain. Among 1,819 patients
      (82.2%) who underwent coronary angiography, 1,652 patients (90.8%) showed a
      coronary and 167 patients (9.2%) a non-coronary origin of chest pain. 901
      patients (54.5%) presented with an ACS, 751 (45.5%) with a stable angina
      pectoris. Clinical outcome was performed by a predefined structured telephone
      interview after a 3-month follow-up (92.8%:1,533 of 1,652 patients). RESULTS:
      Kaplan-Meier analysis for cumulative event-free survival revealed that patients
      with a elevated baseline GPVI expression had a poorer clinical outcome for
      cardiovascular death than patients with decreased GPVI levels (log rank; P =
      0.040). These results were paralleled in composite cumulative survival that
      included myocardial infarction, stroke, and cardiovascular death (log rank; P =
      0.002). Relative risk of cardiovascular death was found at 1.41 (95% CI 1.08
      1.85) for platelet GPVI, 1.64 (95% CI 1.31-2.05) for brain natriuretic peptide,
      1.16 (95% CI 0.81-1.64) for troponin-I and 1.33 (95% CI 0.97-1.82) for C-reactive
      protein. CONCLUSIONS: Patients with CAD presenting increased levels of platelet
      GPVI had a poorer outcome and may profit from a dual antiplatelet therapy. Thus,
      GPVI may be a useful prognostic tool for adverse cardiovascular events. Future
      studies should substantiate GPVI for its potential role of risk prediction and
      consider its prognostic value to improve risk stratification.

PMID- 20049464
TI  - Balloon valvuloplasty of a tricuspid valve stenosis in double balloon technique.

PMID- 20049465
TI  - Diagnostic superiority of a combined assessment of the systolic and early
      diastolic mitral annular velocities by tissue Doppler imaging for the
      differentiation of restrictive cardiomyopathy from constrictive pericarditis.
AB  - BACKGROUND AND AIMS: Echocardiographic tissue Doppler imaging (TDI) has been
      proposed as diagnostic tool for the differentiation between constrictive
      pericarditis (CP) and restrictive cardiomyopathy (RCM). The aim of this study was
      a comprehensive TDI analysis of systolic (S') and early diastolic (E') velocities
      of the septal and lateral mitral annulus (MA) in patients (pts) with severe
      diastolic dysfunction caused either by CP or RCM. METHODS AND RESULTS: Sixty
      consecutive pts (34 men, mean age 61 +/- 11 years), 34 pts with proven CP and 26
      pts with RCM due to cardiac amyloidosis, were included in the study. Forty-two of
      the 60 pts were in NYHA class III (70%). In pts with RCM systolic longitudinal
      velocity (S') was significantly decreased when compared to CP (septal MA 4.1 +/-
      1.5 vs. 7.3 +/- 2.1 cm/s, p < 0.001; lateral MA 4.3 +/- 1.9 vs. 7.0 +/- 1.9 cm/s,
      p < 0.001). In addition, the RCM group showed a significantly decreased early
      diastolic longitudinal velocity (E'), both on the septal (4.1 +/- 1.6 vs. 12.9 +/
      4.9 cm/s, p < 0.001) and lateral side (4.8 +/- 1.9 vs. 11.3 +/- 3.7 cm/s; p <
      0.001) of the mitral annulus. ROC analysis demonstrated an area under the curve
      of 0.889 (S' septal), 0.823 (S' lateral), 0.974 (E' septal), and 0.915 (E'
      lateral) for the differentiation of RCM and CP with a cutoff value of <8 cm/s.
      The combined use of an averaged S' cutoff value <8 cm/s as well as an E' cutoff
      value <8 at the lateral and septal MA demonstrated 93% sensitivity and 88%
      specificity for the diagnosis of RCM. CONCLUSION: TDI provides a diagnostic
      superiority and an accurate discrimination between RCM and CP by using the
      combined cutoff value of <8 cm/s for S' and E' at both sides of the MA.

PMID- 20049466
TI  - Immunoadsorption in dermatology.
AB  - Immunoadsorption (IA), also termed immunoapheresis, has been established as
      effective and specific tool advantageous to plasmapheresis to remove
      immunoglobulin and immune complexes and in cytapheresis, immune cells from the
      circulation. IA was successfully used in various autoantibody-mediated diseases,
      e.g. acquired hemophilia, myasthenia gravis, dilated cardiomyopathy, and Guillain
      Barre syndrome. In dermatology, IA has been applied as an effective adjuvant
      treatment for autoimmune bullous diseases. Autoimmune blistering disorders are a
      heterogeneous group of diseases that are associated with autoantibodies to
      desmosomal (pemphigus group) and basal membrane zone proteins (pemphigoid group,
      epidermolysis bullosa acquisita). Because the pathogenic relevance of
      autoantibodies was clearly demonstrated in the majority of these disorders,
      removal of autoantibodies, therefore, appears to be a rational therapeutic
      approach for these patients. IA has been shown to effectively lower the
      autoantibody levels and leads to rapid clinical responses in patients with
      immunobullous disorders. Here, clinical effects and adverse events of IA in more
      than 50 reported patients with autoimmune blistering disorders are reviewed. In
      addition, an overview of the available IA systems and treatment protocols is
      provided and guidelines of a recent consensus of German, Austrian, and Swiss
      experts for the use of IA in autoimmune bullous diseases are summarized.

PMID- 20049467
TI  - Ichthyosis in Sjogren-Larsson syndrome reflects defective barrier function due to
      abnormal lamellar body structure and secretion.
AB  - Sjogren-Larsson syndrome is a genetic disease characterized by ichthyosis, mental
      retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty
      aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and
      fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with
      Sjogren-Larsson syndrome to better understand how the enzymatic deficiency
      results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing
      activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion
      studies showed abnormal movement of tracer into the extracellular spaces of the
      stratum corneum consistent with a leaky water barrier. The barrier defect could
      be attributed to the presence of abnormal lamellar bodies, many with disrupted
      limiting membranes or lacking lamellar contents. Entombed lamellar bodies were
      present in the cytoplasm of corneocytes suggesting blockade of lamellar body
      secretion. At the stratum granulosum-stratum corneum interface, non-lamellar
      material displaced or replaced secreted lamellar membranes, and in the stratum
      corneum, the number of lamellar bilayers declined and lamellar membrane
      organization was disrupted by foci of lamellar/non-lamellar phase separation.
      These studies demonstrate the presence of a permeability barrier abnormality in
      Sjogren-Larsson syndrome, which localizes to the stratum corneum interstices and
      can be attributed to abnormalities in lamellar body formation and secretion.

PMID- 20049468
TI  - Ovarian tumors associated with pregnancy: a 20-year experience in a teaching
      hospital.
AB  - OBJECTIVE: Pregnancy associated with ovarian tumors was reviewed over a 20-year
      period to determine the maternal and fetal outcome in patients undergoing surgery
      during pregnancy. METHOD: A retrospective study of 94 cases of ovarian tumors
      treated surgically during pregnancy was investigated for incidence, clinico
      pathological features and outcome in a teaching hospital between June 1987 and
      May 2007. RESULTS: The overall incidence of ovarian tumor in pregnant women was 1
      in 505 (0.2%) deliveries. Diagnosis of 69.2% tumors resulted in the first and
      second trimesters of pregnancy. Twenty-two (23.4%) patients presented as an
      emergency at different periods of gestation and 16 (17.1%) tumors were
      incidentally discovered at cesarean section which underlines the significance of
      examining the ovaries routinely at cesarean section. Benign teratoma (39.4%) and
      serous cystadenoma (24.5%) were the most common types of ovarian tumors found in
      the study. The incidence of malignant tumors was 5.3%. Tumors with low malignant
      potential comprised 40% of malignancy. The miscarriage rate after surgery was
      44.4% in the first trimester compared with 16.6% in the second trimester. The
      preterm birth rate was 4.3% in the series. CONCLUSION: The value of clinical and
      ultrasound examinations in early pregnancy as a diagnostic aid is highlighted.
      Whenever an ovarian tumor is detected in pregnancy, malignancy should always be
      suspected. Treatment of an ovarian tumor in pregnancy should be tailored
      according to the age, parity, clinical presentation, gestational age and
      histopathology of the tumor. Removal of persisting or enlarging ovarian masses as
      soon as possible is important to obtain a final histologic diagnosis and rule out
      malignancy. Early diagnosis and appropriate treatment of malignant tumors offers
      the best prognosis for the patient.

PMID- 20049469
TI  - Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised
      patients with and without AIDS.
AB  - The aim of this study was to compare chest computerized tomography (CT) findings
      of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and
      without acquired immune deficiency syndrome (AIDS). Chest CT findings and
      clinical parameters of 38 consecutive immunocompromised patients, nine with AIDS
      and 29 with other causes of immunosuppression, were characterized and compared.
      PCP in patients without AIDS was diagnosed after a significantly shorter time
      interval from symptom onset: 8 +/- 6 vs. 18 +/- 1.0 days (p = 0.024). From a
      radiographic point of view, non-AIDS patients had a significantly higher
      proportion of diffuse ground glass lesions, 86 vs. 44% (p = 0.02), and a lower
      proportion of cystic lesions, 3 vs. 56% (p = 0.015). The two subgroups did not
      differ in smoking status and the number of pack-years. On multivariant analysis,
      only the presence of AIDS was found to be a risk factor for the formation of
      pulmonary cystic lesions. Different immune reactions to the parasite P. jirovecii
      in immunocompromised patients with and without AIDS results in a different time
      lag between symptoms and a correspondingly different radiographic pattern:
      widespread ground glass opacities in the former and cystic lesions in the latter.

PMID- 20049470
TI  - Volumetric capnography for the evaluation of pulmonary disease in adult patients
      with cystic fibrosis and noncystic fibrosis bronchiectasis.
AB  - This study was designed to use volumetric capnography to evaluate the breathing
      pattern and ventilation inhomogeneities in patients with chronic sputum
      production and bronchiectasis and to correlate the phase 3 slope of the
      capnographic curve to spirometric measurements. Twenty-four patients with cystic
      fibrosis (CF) and 21 patients with noncystic fibrosis idiopathic bronchiectasis
      (BC) were serially enrolled. The diagnosis of cystic fibrosis was based on the
      finding of at least two abnormal sweat chloride concentrations (iontophoresis
      sweat test). The diagnosis of bronchiectasis was made when the patient had a
      complaint of chronic sputum production and compatible findings at high-resolution
      computed tomography (HRCT) scan of the thorax. Spirometric tests and volumetric
      capnography were performed. The 114 subjects of the control group for
      capnographic variables were nonsmoker volunteers, who had no respiratory symptoms
      whatsoever and no past or present history of lung disease. Compared with
      controls, patients in CF group had lower SpO(2) (P < 0.0001), higher respiratory
      rates (RR) (P < 0.0001), smaller expiratory volumes normalized for weight
      (V(E)/kg) (P < 0.028), smaller expiratory times (Te) (P < 0.0001), and greater
      phase 3 Slopes normalized for tidal volume (P3Slp/V(E)) (P < 0.0001). Compared
      with controls, patients in the BC group had lower SpO(2) (P < 0.0001), higher RR
      (P < 0.004), smaller V(E)/kg (P < 0.04), smaller Te (P < 0.007), greater
      P3Slp/V(E) (P < 0.0001), and smaller VCO(2) (P < 0.0002). The pooled data from
      the two patient groups compared with controls showed that the patients had lower
      SpO(2) (P < 0.0001), higher RR (P < 0.0001), smaller V(E)/kg (P < 0.05), smaller
      Te (P < 0.0001), greater P3Slp/V(E) (P < 0.0001), and smaller VCO(2) (P <
      0.0003). All of the capnographic and spirometric variables evaluated showed no
      significant differences between CF and BC patients. Spirometric data in this
      study reveals that the patients had obstructive defects with concomitant low
      vital capacities and both groups had very similar abnormalities. The capnographic
      variables in the patient group suggest a restrictive respiratory pattern (greater
      respiratory rates, smaller expiratory times and expiratory volumes, normal peak
      expiratory flows). Both groups of patients showed increased phase III slopes
      compared with controls, which probably indicates the presence of diffuse disease
      of small airways in both conditions leading to inhomogeneities of ventilation.

PMID- 20049471
TI  - Applications of airway pressure release ventilation.
AB  - The purpose of this review is to cover the definition and mechanism of airway
      pressure release ventilation, its advantages, and applications in acute lung
      injury.

PMID- 20049472
TI  - Clinical characteristics, prognosis, and seropositivity to the anti-aquaporin-4
      antibody in Korean patients with longitudinally extensive transverse myelitis.
AB  - Longitudinally extensive transverse myelitis (LETM) is a syndrome with extensive
      spinal cord lesions spanning three or more vertebral segments on spinal cord MRI.
      Although many reports have indicated that LETM is a characteristic feature of
      neuoromyelitis optica (NMO) in Western countries, the clinical characteristics
      and risk for development of NMO in Korean patients with LETM is not clear. We
      retrospectively investigated the clinical, laboratory, radiological features, and
      prognosis of Korean patients with a first-ever episode of idiopathic LETM.
      Patients were classified into four subgroups, depending on their clinical course:
      monophasic LETM, recurrent LETM, NMO, and classic multiple sclerosis (MS). We
      compared various clinical, laboratory, and radiological features between groups.
      Of 20 patients with first-ever LETM, 15 (75%) were men, and 13 (65%) experienced
      clinical relapse over a mean follow-up period of 58 months. Three of 20 patients
      (two with NMO, one with recurrent myelitis) were seropositive for anti-AQP4
      antibodies. The predominance of men in the monophasic and recurrent LETM groups
      compared to the NMO group was remarkable. In conclusion, Korean patients with
      LETM are predominantly male and have low seropositivity for anti-AQP4 antibody,
      which distinguishes them from LETM patients in Western countries. Patients with
      LETM and seropositivity for anti-AQP4 antibody have a high risk of relapse. The
      male predominance and the relatively low seropositive rate for anti-AQP4 suggests
      that rather than being a limited form of NMO, recurrent LETM is a new clinical
      entity in Koreans.

PMID- 20049473
TI  - Alemtuzumab in the treatment of IVIG-dependent chronic inflammatory demyelinating
      polyneuropathy.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an idiopathic immune
      mediated neuropathy causing demyelination and conduction block thought to occur
      as the result of an aberrant autoimmune response resulting in peripheral nerve
      inflammation mediated by T cells and humoral factors. Diagnosis commonly prompts
      initial treatment with steroids or intravenous immunoglobulin (IVIG) on which 5
      35% subsequently become dependent to maintain function. Despite a number of small
      scale trials, the role for alternative long-term immunosuppression remains
      unclear. Alemtuzumab is a humanised monoclonal antibody targeting the CD52
      antigen present on the surface of lymphocytes and monocytes. A single intravenous
      infusion results in rapid and profound lymphopoenia lasting >12 months. We report
      its use and clinical outcome in a small series of patients with severe IVIG
      dependent CIDP. Seven patients (4 Males; 3 Females) who had failed to respond to
      conventional immunosuppression were treated in 5 centres receiving 9 courses of
      alemtuzumab (dose range 60-150 mg). Following treatment, mean monthly IVIG use
      fell 26% from 202 to 149 g and IVIG administration frequency from 22 to 136 days.
      Two patients had prolonged remission, two patients had a partial response and no
      clear benefit was observed in the remaining three patients (2 Males, 1 Females).
      Responding patients had a younger age at onset (19.5 years) and shorter disease
      duration than non-responders. Three patients developed autoimmune disease
      following treatment. Alemtuzumab may offer an alternative treatment for a subset
      of early onset IVIG dependent CIDP patients failing conventional
      immunosuppressive agents, but concerns about toxicity may limit its use.

PMID- 20049474
TI  - Bilateral central serous chorioretinopathy resolving rapidly with treatment for
      obstructive sleep apnea.
AB  - BACKGROUND: Central serous chorioretinopathy (CSR) is a common disorder that
      affects many individuals, often for unknown reasons; we present a case of
      bilateral CSR that rapidly resolved with treatment of obstructive sleep apnea
      (OSA). METHODS: Observational case report. RESULTS: Bilateral decreased vision to
      20/30 OD and 20/40 OS due to typical CSR lesions. Systemic evaluation led to a
      diagnosis of OSA, which was treated and resulted in rapid resolution of the CSR
      and improvement of visual acuity in both eyes. DISCUSSION: We present the first
      case of rapidly resolving bilateral CSR due to the treatment of OSA.

PMID- 20049475
TI  - "Guidance of macular laser photocoagulation: is fluorescein angiography still
      needed?".

PMID- 20049476
TI  - Nucleolin as cell surface receptor for tumor necrosis factor-alpha inducing
      protein: a carcinogenic factor of Helicobacter pylori.
AB  - PURPOSE: Tumor necrosis factor-alpha inducing protein (Tipalpha) is a unique
      carcinogenic factor released from Helicobacter pylori (H. pylori). Tipalpha
      specifically binds to cells and is incorporated into cytosol and nucleus, where
      it strongly induces expression of TNF-alpha and chemokine genes mediated through
      NF-kappaB activation, resulting in tumor development. To elucidate mechanism of
      action of Tipalpha, we studied a binding protein of Tipalpha in gastric
      epithelial cells. METHODS: Tipalpha binding protein was found in cell lysates of
      mouse gastric cancer cell line MGT-40 by FLAG-pull down assay and identified to
      be cell surface nucleolin by flow cytometry using anti-nucleolin antibody.
      Incorporation of Tipalpha into the cells was determined by Western blotting and
      expression of TNF-alpha gene was quantified by RT-PCR. RESULTS: Nucleolin was co
      precipitated with Tipalpha-FLAG, but not with del-Tipalpha-FLAG (an inactive
      mutant). After treatment with Tipalpha-FLAG, incorporated Tipalpha was co
      immunoprecipitated with endogenous nucleolin using anti-nucleolin antibody. The
      direct binding of Tipalpha to recombinant His-tagged nucleolin fragment (284-710)
      was also confirmed. Although nucleolin is an abundant non-ribosomal protein of
      the nucleolus, we found that nucleolin is present on the cell surface of MGT-40
      cells. Pretreatment with anti-nucleolin antibody enhanced Tipalpha-incorporation
      into the cells through nucleolin internalization. In addition, pretreatment with
      tunicamycin, an inhibitor of N-glycosylation, decreased the amounts of cell
      surface nucleolin and inhibited both internalization of Tipalpha and expression
      of TNF-alpha gene. CONCLUSIONS: All the results indicate that nucleolin acts as a
      receptor for Tipalpha and shuttles Tipalpha from cell surface to cytosol and
      nuclei. These findings provide a new mechanistic insight into gastric cancer
      development with Tipalpha.

PMID- 20049477
TI  - A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase
      gene (NOS3) and their effect on the risk of diabetic nephropathy.
AB  - A number of association studies have investigated the role of the nitric oxide
      synthase 3 (NOS3) gene in the development of diabetic nephropathy (DN). However,
      results have been inconclusive, largely because the studies have focused on a
      variety of different polymorphisms and generate inconsistent results. We
      performed a meta-analysis of 28 association studies focusing on three
      polymorphisms in the NOS3 gene (G894T (Glu289Asp), 4b/a, and T-786C) and the risk
      of DN published before July 2009, covering a total of 10,364 subjects. Although
      significant heterogeneity was initially found in the analysis of G894T, it did
      not remain when analysis was done by ethnic subgroups. 894T was negatively
      associated with DN in Caucasian populations of European origin (OR = 0.896, 0.817
      0.983, 95% CI), but was positively associated with DN in East Asian (OR = 2.02,
      1.20-3.42, 95% CI) and other populations. Association of the 4b/a variant was
      observed when studies involving microalbuminuria were excluded (OR = 1.19, 1.02
      1.39, 95% CI). The T-786C variant showed an overall weak association (OR = 1.16,
      1.01-1.34, 95% CI) with little heterogeneity. In summary, our meta-analysis of
      the effect of NOS3 gene polymorphisms on the risk of DN supports the involvement
      of the NOS3 gene in the pathogenesis of DN.

PMID- 20049478
TI  - Intraspecific alkaloid variation in ladybird eggs and its effects on con- and
      hetero-specific intraguild predators.
AB  - Egg predation and cannibalism are common phenomena in predatory ladybirds despite
      the presence of defensive alkaloids. Consumption of heterospecific eggs
      negatively affects survivorship and development; however, intraspecific variation
      in quantities of alkaloids and post-ingestion responses to con- and hetero
      specific alkaloids, are not well understood. We examined variation in the
      quantity of alkaloids in eggs of Harmonia axyridis (Pallas), Coccinella
      septempunctata L., and Hippodamia convergens (Guerin) using gas chromatography
      mass spectrometry, and show a link between heterospecific alkaloids and their
      toxicity and/or costs by feeding high and low alkaloid eggs to first instar H.
      axyridis and C. septempunctata. The repeatability of alkaloid measurements in
      eggs in an egg cluster was high; however, the amount of alkaloids varied
      significantly between egg clutches within and among females. This variation
      affected egg consumption by C. septempunctata when fed H. axyridis eggs. Harmonia
      axyridis accumulated their own alkaloid by cannibalism and synthesized it de
      novo, but C. septempunctata lost some portion of the consumed conspecific
      alkaloids. Both species lost most of the consumed heterospecific alkaloids, but
      C. septempunctata died within 3 days. Most H. axyridis survived to the second
      instar, but C. septempunctata alkaloids led to a significant reduction in weight
      gain compared to an aphid control. In addition, ingestion of high alkaloid C.
      septempunctata extended development of H. axyridis compared to the aphid control
      or conspecific eggs. Harmonia axyridis had greater abilities to process ingested
      con- and hetero-specific alkaloids compared with C. septempunctata, which may, in
      part, explain their interspecific interactions in nature.

PMID- 20049479
TI  - Bird diversity and seed dispersal along a human land-use gradient: high seed
      removal in structurally simple farmland.
AB  - Only few studies have analysed the relationship between biodiversity and
      ecosystem function at the landscape scale although relationships and mechanisms
      known from experimental studies might be different in natural systems. We
      quantified bird diversity and seed removal from 38 wild cherry trees (Prunus
      avium) along a human land-use gradient from forest to structurally diverse to
      simple agricultural systems. High human land-use intensity led to low species
      richness and total abundance of the local bird community around wild cherry
      trees, as expected from previous studies. Nevertheless, trees in structurally
      simple agroecosystems were visited as frequently as trees in structurally complex
      landscapes and in forests. Furthermore, the number of seeds removed per tree did
      not decline with increasing human land-use intensity. Thus, ecosystem function
      was robust in spite of locally reduced bird diversity. The reason might be that
      movement behaviour and movement distances of birds changed along the human land
      use gradient. It appears that birds moved longer distances to forage in fruiting
      cherry trees in structurally simple agroecosystems. This suggests that for
      systems where ecosystem function is mediated by highly mobile organisms, movement
      behaviour and distances are of considerable importance. Increases in movement
      distances with increasing human land-use intensity might also be common in other
      systems in which ecosystem function depends on mobile links.

PMID- 20049480
TI  - A strong conditional mutualism limits and enhances seed dispersal and germination
      of a tropical palm.
AB  - Seed predation and seed dispersal can have strong effects on early life history
      stages of plants. These processes have often been studied as individual effects,
      but the degree to which their relative importance co-varies with seed predator
      abundance and how this influences seed germination rates is poorly understood.
      Therefore, we used a combination of observations and field experiments to
      determine the degree to which germination rates of the palm Astrocaryum mexicanum
      varied with abundance of a small mammal seed predator/disperser, Heteromys
      desmarestianus, in a lowland tropical forest. Patterns of abundance of the two
      species were strongly related; density of H. desmarestianus was low in sites with
      low density of A. mexicanum and vice versa. Rates of predation and dispersal of
      A. mexicanum seeds depended on abundance of H. desmarestianus; sites with high
      densities of H. desmarestianus had the highest rates of seed predation and lowest
      rates of seed germination, but a greater total number of seeds were dispersed and
      there was greater density of seedlings, saplings, and adults of A. mexicanum in
      these sites. When abundance of H. desmarestianus was experimentally reduced,
      rates of seed predation decreased, but so did dispersal of A. mexicanum seeds.
      Critically, rates of germination of dispersed seeds were 5 times greater than
      undispersed seeds. The results suggest that the relationship between A. mexicanum
      and H. desmarestianus is a conditional mutualism that results in a strong local
      effect on the abundance of each species. However, the magnitude and direction of
      these effects are determined by the relative strength of opposing, but related,
      mechanisms. A. mexicanum nuts provide H. desmarestianus with a critical food
      resource, and while seed predation on A. mexicanum nuts by H. desmarestianus is
      very intense, A. mexicanum ultimately benefits because of the relatively high
      germination rates of its seeds that are dispersed by H. desmarestianus.

PMID- 20049481
TI  - Comparison of gas exchange data using the Aquatrainer system and the facemask
      with Cosmed K4b2 during exercise in healthy subjects.
AB  - The aim of this study was to determine the level of agreement between the new
      Aquatrainer system and the facemask in the assessment of submaximal and maximal
      cardiopulmonary responses during exercise performed on ergocycle. Twenty-six
      physically active healthy subjects (mean age: 41 +/- 14 years) performed a
      submaximal constant work test followed by maximal incremental exercise test on
      ergocycle, one with cardiopulmonary responses measured using the Cosmed K4b2
      facemask, the other using the Cosmed K4b2 Aquatrainer. Using the Aquatrainer, the
      gas exchange variables at 100 W were significantly lower for VO(2) (1,483 +/- 203
      vs. 1,876 +/- 204 ml min(-1), P < 0.0001), VCO(2) (1,442 +/- 263 vs. 1,749 +/-
      231 ml min(-1), P < 0.0001), VE (38 +/- 5 vs. 44 +/- 6 l min(-1), P < 0.0001),
      and VT (1.92 +/- 0.47 vs. 2.18 +/- 0.41 l, P < 0.0001) relative to facemask. The
      bias +/-95% limits of agreement (LOA) for VO(2) was 393 +/- 507 ml min(-1) for
      the submaximal constant work test at 100 W and 495 +/- 727 ml min(-1) for
      VO(2max). At maximal intensity, cardiopulmonary responses measured with the
      Aquatrainer system were significantly lower for: VO(2) (2,799 +/- 751 vs. 3,294
      +/- 821 ml min(-1), P < 0.0001), VCO(2) (3,426 +/- 836 vs. 3,641 +/- 946 ml min(
      1), P = 0.012), VE (98 +/- 21 vs. 108 +/- 26 l min(-1), P = 0.0009) relative to
      facemask. A non-constant measurement error [interaction effect: (facemask or
      aquatrainer) x power] was noted from 60 to 270 W for VO(2) (ml min(-1)), VCO(2)
      (ml min(-1)), ventilation (l min(-1)) (P < 0.0001) and VT (l, P = 0.0001).
      Additional studies are required to detect the main sources of error that could be
      physical and/or physiological in nature. Due to the significant measurement
      error, the new Aquatrainer system should be used with extreme caution in filed
      testing conditions of swimmers.

PMID- 20049482
TI  - AQP1 mediates water transport in the carotid body.
AB  - In this study, we explored the presence of aquaporins (AQPs), a family of
      membrane water channel proteins, in carotid body (CB) type I chemoreceptor cells.
      The CB is a polymodal chemoreceptor whose major function is to detect changes in
      arterial O2 tension to elicit hyperventilation during hypoxia. The CB has also
      been proposed to function as a systemic osmoreceptor, thus we hypothesized that
      the presence of AQPs in type I cell membrane may confer higher sensitivity to
      osmolarity changes and hence accelerate the activation of chemoreceptor cells. We
      detected the expression of AQP1, AQP7, and AQP8 in the CB and confirmed the
      location of AQP1 in type I cells. We have also shown that inhibition of AQP1
      expression clearly reduced type I cell swelling after a hyposmotic shock,
      demonstrating that AQP1 has a major contribution in transmembrane water movement
      in these chemoreceptor cells. Interestingly, CB AQP1 expression levels change
      during postnatal development, increasing during the first postnatal weeks as the
      organ matures. In conclusion, in this study, we report the novel observation that
      AQPs are expressed in the CB. We also show that AQP1 mediates water transport
      across the cell membrane of type I cells, supporting the contribution of this
      protein to the osmoreception function of the CB.

PMID- 20049484
TI  - Excess deaths during the 2004 heatwave in Brisbane, Australia.
AB  - The paper examines whether there was an excess of deaths and the relative role of
      temperature and ozone in a heatwave during 7-26 February 2004 in Brisbane,
      Australia, a subtropical city accustomed to warm weather. The data on daily
      counts of deaths from cardiovascular disease and non-external causes,
      meteorological conditions, and air pollution in Brisbane from 1 January 2001 to
      31 October 2004 were supplied by the Australian Bureau of Statistics, Australian
      Bureau of Meteorology, and Queensland Environmental Protection Agency,
      respectively. The relationship between temperature and mortality was analysed
      using a Poisson time series regression model with smoothing splines to control
      for nonlinear effects of confounding factors. The highest temperature recorded in
      the 2004 heatwave was 42 degrees C compared with the highest recorded temperature
      of 34 degrees C during the same periods of 2001-2003. There was a significant
      relationship between exposure to heat and excess deaths in the 2004 heatwave
      [estimated increase in non-external deaths: 75 ([95% confidence interval, CI: 11
      138; cardiovascular deaths: 41 (95% CI: -2 to 84)]. There was no apparent
      evidence of substantial short-term mortality displacement. The excess deaths were
      mainly attributed to temperature but exposure to ozone also contributed to these
      deaths.

PMID- 20049483
TI  - ClC transporters: discoveries and challenges in defining the mechanisms
      underlying function and regulation of ClC-5.
AB  - The involvement of several members of the chloride channel (ClC) family of
      membrane proteins in human disease highlights the need to define the mechanisms
      underlying their function and the consequences of disease-causing mutations.
      Despite the utility of high-resolution structural models, our understanding of
      the molecular basis for function of the chloride channels and transporters in the
      family remains incomplete. In this review, we focus on recent discoveries
      regarding molecular mechanisms underlying the regulated chloride:proton
      antiporter activity of ClC-5, the protein mutated in the Dent's disease-a kidney
      disease presenting with proteinuria and renal failure in severe cases. We discuss
      the putative role of ClC-5 in receptor-mediated endocytosis and protein uptake by
      the proximal renal tubule and the possible molecular and cellular consequences of
      disease-causing mutations. However, validation of these models will require
      future study of the intrinsic function of this transporter, in situ, in the
      membranes of recycling endosomes in proximal tubule epithelial cells.

PMID- 20049485
TI  - Protein profiles of peripheral blood mononuclear cells are useful for
      differential diagnosis of ulcerative colitis and Crohn's disease.
AB  - BACKGROUND: Effective biomarkers for discrimination between ulcerative colitis
      (UC) and Crohn's disease (CD) have not been established yet. In this study, we
      analyzed protein profiles of peripheral blood mononuclear cells (PBMCs) of the
      patients to find such a biomarker. METHODS: Peripheral blood mononuclear cell
      proteins from 17 UC patients, 13 CD patients, and 17 healthy controls were
      separated by two-dimensional gel electrophoresis. The intensities of individual
      protein spots were subjected to discriminant analysis of UC and CD using the
      SIMCA-P+program. RESULTS: We found that 547 protein spots were commonly detected
      among the UC, CD, and healthy groups. Orthogonal partial least squares
      discriminant analysis using 276 protein spots clearly discriminated the UC
      patients from the CD patients (R (2) 0.994; Q (2) 0.462). A similar analysis
      using a further selected 58 protein spots showed higher performance for
      discrimination of the diseases (R (2) 0.948; Q (2) 0.566). Eleven out of the 58
      protein spots were successfully identified; these were functionally related to
      inflammation, oxidation/reduction, the cytoskeleton, endocytotic trafficking, and
      transcription. In addition, the PBMC protein profiles were useful for the
      prediction of disease activity in the UC and the CD patients, and they were also
      useful for predicting disease severity and responses to treatments in the UC
      patients. CONCLUSIONS: PBMC protein profiles are useful for the discrimination of
      UC from CD. The profiles could be a potent biomarker for the differential
      diagnosis of these diseases. Further investigation of the proteins which
      contributed to the discrimination could promote elucidation of the
      pathophysiology of UC and CD.

PMID- 20049487
TI  - Intramedullary lumbar lesion mimicking spinal cord tumor: a case of non
      neoplastic intramedullary spinal cord lesion.
AB  - Non-neoplastic intramedullary spinal lesion cases are rarely seen in the
      literature. We would like to present this case for differential diagnosis of
      intramedullary spinal tumors. The aim of this case report is to attract attention
      on the MRI findings with lack of contrast enhancement and long syrinx formation
      which differs these types of lesions from the intramedullary spinal tumors.
      Intraoperative, pathological and immunohistochemical findings of non-neoplastic
      intramedullary spinal lesion were discussed.

PMID- 20049486
TI  - Posterior decompression with instrumented fusion for thoracic myelopathy caused
      by ossification of the posterior longitudinal ligament.
AB  - We evaluated the clinical results of posterior decompression with instrumented
      fusion (PDF) for thoracic myelopathy due to ossification of the posterior
      longitudinal ligament (OPLL). A total of 24 patients underwent PDF, and their
      surgical outcomes were evaluated by the Japanese Orthopaedic Association (JOA)
      scores (0-11 points) and by recovery rates calculated at 3, 6, 9 and 12 months
      after surgery and at a mean final follow-up of 4 years and 5 months. The mean JOA
      score before surgery was 3.7 points. Although transient paralysis occurred
      immediately after surgery in one patient (3.8%), all patients showed neurological
      recovery at the final follow-up with a mean JOA score of 8.0 points and a mean
      recovery rate of 58.1%. The mean recovery rate at 3, 6, 9 and 12 months after
      surgery was 36.7, 48.8, 54.0 and 56.8%, respectively. The median time point that
      the JOA score reached its peak value was 9 months after surgery. No patient chose
      additional anterior decompression surgery via thoracotomy. The present findings
      demonstrate that despite persistent anterior impingement of the spinal cord by
      residual OPLL, PDF can result in considerable neurological recovery with a low
      risk of postoperative paralysis. Since neurological recovery progresses slowly
      after PDF, we suggest that additional anterior decompression surgery is not
      desirable during the early stage of recovery.

PMID- 20049488
TI  - Natura abhorret a vacuo--use of fibrin glue as a filler and sealant in
      neurosurgical "dead spaces". Technical note.
AB  - OBJECTIVE: The objective of this study is to report our experience and illustrate
      our technique in the use of fibrin glue in the treatment of post-operatory
      cerebrospinal fluid (CSF) leaks and collections following different neurosurgical
      procedures. METHODS: In a 3-year period, 40 subjects underwent endoscopic
      endonasal approach for different sellar and skull base lesions (three tuberculum
      sellae meningiomas, six craniopharyngiomas, three Rathke's cleft cysts and 28
      pituitary macroadenomas), in which an intraoperative CSF leakage was evident. In
      such subjects, the fibrin glue was used as a first step of the final phase of the
      procedure-i.e. the reconstruction of the skull base defect-followed by the other
      materials employed. Furthermore, ten other patients, who had undergone
      transsphenoidal (four cases), spinal (two cases), posterior fossa (three cases)
      and transcortical intraventricular tumour removal (one case) neurosurgical
      procedures and developed CSF leaks or collections, were conservatively treated by
      single or repeated in situ injections of "modified" fibrin glue under local
      anaesthesia according to different described techniques. In total, 50 patients
      constitute the clinical material of the present study. TECHNIQUE: In the cases
      where the fibrin glue was used during the reconstruction phase of the procedure
      (40 cases), the glue was injected inside the tumour cavity to fill the dead space
      left by the removal of the lesion. In case of post-operative CSF leak or CSF
      fluid collection (ten cases), after discarding 50-80% of the thrombin solution to
      obtain prevalence of the product's adhesive properties, fibrin glue was injected
      directly in the path of the CSF leak or into the collection cavity after
      aspiration of the collection's content. This was performed with the provided
      application system or through lumbar or Tuohy needles. Applications were repeated
      every 48 h until the disappearance of the leak. In all the treated cases, the
      disappearance of CSF leaks or collections was obtained with a number of
      applications ranging from one to five. Successful results are stable with a
      follow-up ranging from 6 months to 3 years. CONCLUSIONS: In our experience, the
      injection of fibrin glue has proved to be effective in filling or sealing post
      operative "dead spaces" and treating minor or initial CSF leaks resulting from
      procedures of transsphenoidal, cranial and spinal surgery, adding another
      possibility in the management of many of these dreadful complications.

PMID- 20049489
TI  - Neurosurgical biopsy as the initial diagnosis of xanthogranuloma of the Erdheim
      Chester disease variety of the infundibulum and optic apparatus: letter to the
      editor.

PMID- 20049490
TI  - Response to methylphenidate is not influenced by DAT1 polymorphisms in a sample
      of Brazilian adult patients with ADHD.
AB  - Several lines of evidence suggest a relevant role for the dopamine transporter
      (DAT1) gene not only as a susceptibility factor for attention-deficit
      hyperactivity disorder (ADHD), but also as a predictor of individual
      methylphenidate (MPH) response. Pharmacogenetic studies of MPH response in ADHD
      have mainly focused on the 40-bp variable number of tandem repeats (VNTR) in the
      3' untranslated region (3'-UTR) of DAT1. Most studies were performed in samples
      of children and conflicting findings were obtained. Only two studies have
      assessed 3'-VNTR in samples of adults-one with positive and the other with
      negative findings. In the present study, we investigate three potentially
      relevant polymorphisms in DAT1 gene (-839 C > T; Int8 VNTR and 3'-VNTR), and
      their possible role in therapeutic response to MPH treatment in a sample of 171
      Brazilian adults with ADHD. The diagnostic procedures followed the DSM-IV
      criteria and the outcome measures were the scales Swanson, Nolan, and Pelham
      Rating scale version IV and the Clinical Global Impression-Severity Scale,
      applied at the beginning and after the 30th day of treatment. Drug response was
      assessed by both categorical and dimensional approaches. There was no effect of
      any DAT1 polymorphisms or haplotypes on MPH response. This is the second report
      demonstrating absence of differences in MPH response according to DAT1 genotypes
      in adults with ADHD. Although DAT protein is crucial for the effect of MPH,
      genetic variations in DAT1 gene probably do not have a significant clinical role
      in this sample of adults with ADHD.

PMID- 20049491
TI  - Comparative placebo-controlled polysomnographic and psychometric studies on the
      acute effects of gabapentin versus ropinirole in restless legs syndrome.
AB  - The aim of the present placebo-controlled sleep laboratory study was to compare
      the acute effects of gabapentin (GBT) and ropinirole (ROP) in restless legs
      syndrome (RLS). In a parallel-group design, 40 RLS patients received 300 mg GBT
      and another 40 patients 0.5 mg ROP as compared with placebo. Polysomnographic and
      psychometric measures were obtained in three sleep laboratory nights
      (screening/placebo/drug). Statistics included a Wilcoxon test for differences
      between drug and placebo and a U test for inter-group differences. Sleep
      efficiency and latency were found significantly improved after GBT, while they
      remained unchanged after ROP, with significant inter-drug differences. Sleep
      architecture showed oppositional changes after the two drugs: While GBT decreased
      S1, increased slow-wave sleep and SREM and shortened REM latency, ROP increased
      S2, decreased slow-wave sleep and SREM and increased REM latency. Periodic leg
      movements (PLM) showed a significantly greater decrease after ROP (-73%) than
      after GBT (-35%). Subjective sleep quality improved significantly only after GBT;
      mental performance improved after both drugs with no inter-drug differences. In
      conclusion, the dopamine agonist ROP showed acute therapeutic efficacy with
      regard to PLM measures only, whereas GBT had a less pronounced effect on these
      measures, but improved objective and subjective sleep and awakening quality as
      compared with both placebo and ROP. Differential acute drug effects may serve as
      prognostic indicators of therapeutic response of individual patients.

PMID- 20049492
TI  - Perinatal use of anticonvulsants: differences in attitudes and recommendations
      among neurologists and psychiatrists.
AB  - We surveyed opinions and recommendations about perinatal anticonvulsant (AC)
      treatment among 166 neurologists (n = 88) and psychiatrists (n = 78) practicing
      in Massachusetts. They were similar in the recommendation of routinely informing
      patients of potential teratogenic risks of ACs and avoiding valproate during
      pregnancy. Neurologists were more likely to encourage pregnancy and nursing
      during AC-use than psychiatrists, and psychiatrist were more cautious regarding
      perinatal safety, citing potential neurobehavioral risks and complications of
      breastfeeding. These observations indicate substantial differences in opinions
      between psychiatrists and neurologists regarding AC use during pregnancy.

PMID- 20049493
TI  - Marginal seal stability of one bottle adhesives in Class V vs. Class I cavities.
AB  - The aim of this study was to test the influence of two different cavity
      configurations on marginal stability of recent one bottle "etch & rinse" and
      "self-etch" adhesives in Class V vs. Class I cavities, before and after thermo
      mechanical loading under simulation of dentinal fluid. Forty human upper molars
      were selected and assigned to five experimental groups. Intrapulpal pressure was
      maintained during cavity preparation, restoration placement, finishing and
      stressing. Standardized Class I and V-Shaped Class V cavities were prepared on
      each tooth. Half of the margins of Class V cavities were located in enamel and
      half in dentin. All cavities were restored with different adhesives systems and a
      nano-hybrid composite. Materials were light-cured using a LED unit. Restored
      teeth were loaded in a computer-controlled chewing machine with 1.2 million
      mechanical occlusal cycles simultaneously with 3,000 thermal cycles (5-50-5
      degrees C). Impressions were made with polyvinylsiloxane of each restoration
      before and after loading. Gold-coated epoxy replicas were prepared for SEM
      examination at *200 magnification. Significant differences between materials were
      found both before and after loading (Kruskal-Wallis, Bonferroni, p < 0.05).
      Significant differences were also found between Class I and V restorations
      (Wilcoxon Matched-Pairs Signed-Rank Test, p < 0.05). Even before thermo
      mechanical loading, none of the groups had 100% continuous margin. Marginal seal
      stability of recent one bottle "etch & rinse" and "self-etch" adhesives are
      significantly different and susceptible to cavity configuration.

PMID- 20049494
TI  - Development of digital shade guides for color assessment using a digital camera
      with ring flashes.
AB  - Digital photographs taken with cameras and ring flashes are commonly used for
      dental documentation. We hypothesized that different illuminants and camera's
      white balance setups shall influence color rendering of digital images and affect
      the effectiveness of color matching using digital images. Fifteen ceramic disks
      of different shades were fabricated and photographed with a digital camera in
      both automatic white balance (AWB) and custom white balance (CWB) under either
      light-emitting diode (LED) or electronic ring flash. The Commission
      Internationale d'Eclairage L*a*b* parameters of the captured images were derived
      from Photoshop software and served as digital shade guides. We found
      significantly high correlation coefficients (r2 > 0.96) between the respective
      spectrophotometer standards and those shade guides generated in CWB setups.
      Moreover, the accuracy of color matching of another set of ceramic disks using
      digital shade guides, which was verified by ten operators, improved from 67% in
      AWB to 93% in CWB under LED illuminants. Probably, because of the inconsistent
      performance of the flashlight and specular reflection, the digital images
      captured under electronic ring flash in both white balance setups revealed less
      reliable and relative low-matching ability. In conclusion, the reliability of
      color matching with digital images is much influenced by the illuminants and
      camera's white balance setups, while digital shade guides derived under LED
      illuminants with CWB demonstrate applicable potential in the fields of color
      assessments.

PMID- 20049495
TI  - Effects of metallic or translucent matrices for Class II composite restorations:
      4-year clinical follow-up findings.
AB  - This study evaluated the performance of composite restorations placed with two
      matrix and wedge systems 4 years after placement. In a split-mouth design, 23
      patients were selected and received at least two class II restorations, one with
      metallic matrix and wooden wedge and the other with polyester matrix and
      reflective wedge. One dentist placed the 109 restorations, and all cavities were
      restored using Single Bond and P-60 (3M ESPE) according to the manufacturer's
      instructions. Polymerization was performed through occlusal (metallic matrices)
      or through the reflective wedge (polyester matrices). Restorations were evaluated
      and categorized as alpha (A), bravo (B), charlie (C), and delta (D; modified
      United States Public Health System criteria) at baseline and 4 years after
      placement. Both clinical aspects and interproximal radiographs were considered in
      the evaluation. Data were analyzed with Mann-Whitney and Friedman tests (alpha =
      0.05). Fifteen subjects (78 teeth/102 proximal surfaces) were reassessed after 4
      years. Considering comparisons within matrices in different evaluation time
      points, no significant differences were observed (p > 0.05). Comparing 4-year to
      baseline results, the quality of marginal adaptation (40% and 40.4 %, score A),
      marginal staining (31.3% and 28.8%, score A), and roughness (56% and 46.2%, score
      A) decreased for metallic and translucent matrices, respectively (p < 0.05),
      while color match (9.6%, score A), occlusal contacts (75%, score A), and proximal
      contacts (71.7%, score A) also decreased in quality for translucent matrices (p <
      0.001). Although the matrix and wedge systems evaluated showed similar clinical
      performance, there was clinical quality loss after 4 years, with most of the
      restorations being still acceptable, and no intervention was necessary.

PMID- 20049496
TI  - Prevalence of dental caries in children with neurofibromatosis 1.

PMID- 20049497
TI  - Fracture behaviour of implant-implant- and implant-tooth-supported all-ceramic
      fixed dental prostheses utilising zirconium dioxide implant abutments.
AB  - This in vitro study investigated the fracture behaviour of implant-implant
      supported and implant-tooth-supported all-ceramic fixed dental prostheses (FDP)
      using zirconium dioxide implant abutments (FRIADENT(r) CERCON(r) abutments,
      DENTSPLY Friadent). Six different test groups (n = 8) were prepared. Groups 1, 2,
      4, and 5 represented an implant-implant-supported FDP condition, whereas groups 3
      and 6 simulated an implant-tooth-supported FDP condition. The second right
      premolar of the mandible was replaced with a pontic tooth. In groups 2 and 5,
      implant abutments were individualised by circumferential preparation. XiVe(r) S
      plus screw implants (DENTSPLY Friadent) that were 4.5 mm (first molar) and 3.8 mm
      (first premolar) in diameter and 11 mm in length and metal tooth analogues with
      simulated periodontal mobility, representing the first right premolar, were
      mounted in a polymethyl methacrylate block. The FDPs were cemented with KetacCem
      (3 M Espe GmbH, Germany). Groups 4, 5, and 6 were thermomechanically loaded
      (thermal and mechanical cycling (TCML) = 1.2 * 106; 10,000 * 5 degrees /55
      degrees ) and subjected to static loading until failure. Statistical analysis of
      data obtained for the force at fracture was performed using non-parametric tests.
      All samples tested survived TCML. In the implant-implant-supported groups,
      circumferential abutment preparation resulted in a tendency to lower fracture
      forces compared to groups with unprepared abutments (group 1, 472.75 +/- 24.71 N;
      group 2, 423.75 +/- 48.48 N; group 4, 647.13 +/- 39.10 N; group 5, 555.86 +/-
      30.34 N). The implant-tooth-supported restorations exhibited higher fracture
      loads (group 3, 736.25 +/- 82.23 N; group 6, 720.75 +/- 48.99 N) than the implant
      implant-supported restorations which did not possess circumferentially
      individualised abutments. Statistically significant differences were found when
      comparing the non-artificially aged groups. Implant-tooth-supported FDP
      restorations did exhibit an increased fracture load compared to implant-implant
      supported FDP restorations.

PMID- 20049498
TI  - QSPR modeling of thermal stability of nitroaromatic compounds: DFT vs. AM1
      calculated descriptors.
AB  - The quantitative structure-property relationship (QSPR) methodology was applied
      to predict the decomposition enthalpies of 22 nitroaromatic compounds, used as
      indicators of thermal stability. An extended series of descriptors
      (constitutional, topological, geometrical charge related and quantum chemical)
      was calculated at two different levels of theory: density functional theory (DFT)
      and semi-empirical AM1 approaches. Reliable models have been developed for each
      level, leading to similar correlations between calculated and experimental data
      (R(2) > 0.98). Hence, both of them can be employed as screening tools for the
      prediction of thermal stability of nitroaromatic compounds. If using the AM1
      model presents the advantage to be less time consuming, DFT allows the
      calculation of more accurate molecular quantum properties, e.g., conceptual DFT
      descriptors. In this study, our best QSPR model is based on such descriptors,
      providing more chemical comprehensive relationships with decomposition
      reactivity, a particularly complex property for the specific class of
      nitroaromatic compounds.

PMID- 20049499
TI  - Exploration of the mechanism for LPFFD inhibiting the formation of beta-sheet
      conformation of A beta(1-42) in water.
AB  - The main component of senile plaques found in AD brain is amyloid beta-peptide (A
      beta), and the neurotoxicity and aggregation of A beta are associated with the
      formation of beta-sheet structure. Experimentally, beta sheet breaker (BSB)
      peptide fragment Leu-Pro-Phe-Phe-Asp (LPFFD) can combine with A beta, which can
      inhibit the aggregation of A beta. In order to explore why LPFFD can inhibit the
      formation of beta-sheet conformation of A beta at atomic level, first, molecular
      docking is performed to obtain the binding sites of LPFFD on the A beta(1-42)
      (LPFFD/A beta(1-42)), which is taken as the initial conformation for MD
      simulations. Then, MD simulations on LPFFD/A beta(1-42) in water are carried out.
      The results demonstrate that LPFFD can inhibit the conformational transition from
      alpha-helix to beta-sheet structure for the C-terminus of A beta(1-42), which may
      be attributed to the hydrophobicity decreasing of C-terminus residues of A beta(1
      42) and formation probability decreasing of the salt bridge Asp23-Lys28 in the
      presence of LPFFD.

PMID- 20049500
TI  - The modified Nyhus-Condon femoral hernia repair.
AB  - PURPOSE: When encountered, a femoral hernia requires repair due to its propensity
      for incarceration with associated morbidity and mortality. Several operations
      have been described, including the low approach (Lockwood), the high approach
      (Lotheisen) and McEvedy's preperitoneal approach. Recently, laparoscopic repair
      has also been advocated. The Nyhus-Condon repair, a transverse abdominal
      preperitoneal repair, was first employed in 1943 and has been widely used since.
      The aim of this study was to describe our modification of the Nyhus-Condon
      repair. METHODS: A retrospective review of all patients who underwent this repair
      over an 18-year period was performed. RESULTS: Twenty-seven patients were
      included in the study. The female:male ratio was 16:11. Sixteen operations were
      performed as emergencies. Four patients required resection of a segment of bowel,
      which was performed through the same incision. There were no immediate post
      operative complications. No recurrence was noted with a median follow-up of 4
      years. CONCLUSION: The Nyhus-Condon repair offers an alternative approach to
      femoral hernia repair and has the advantages of allowing bowel resection through
      the same incision with a better cosmetic outcome than the alternative
      preperitoneal McEvedy repair.

PMID- 20049502
TI  - Commentary on Fontaine et al.: "Safety and efficacy of deep brain stimulation in
      refractory cluster headache: a randomized placebo-controlled double-blind trial
      followed by a 1-year open extension".

PMID- 20049501
TI  - Diagnostic value of anti-cyclic citrullinated peptide antibodies in northern
      Chinese Han patients with rheumatoid arthritis and its correlation with disease
      activity.
AB  - This study was to evaluate the diagnostic value of anti-cyclic citrullinated
      peptide (CCP) antibodies in northern Chinese Han patients with rheumatoid
      arthritis (RA) and its correlation with disease activity. Clinical data and serum
      samples were collected from 112 RA patients and 55 non-RA patients. Statistical
      analyses of the correlations among anti-CCP antibodies, other serological
      markers, and the RA patients' clinical characteristics were performed using SPSS
      11.5 software. Anti-CCP antibodies were detected in 77.7% of all RA patients and
      80.4% of the RA patients with a disease duration of 3 years or less. The combined
      diagnosis using high titer anti-CCP antibodies (>or=100 RU/ml) with a concomitant
      positive rheumatoid factor (RF) test exhibited the greatest diagnostic
      specificity; it achieved 87.9% for all RA patients and 90.1% for the patients
      with disease duration of three years or less. Moreover, anti-CCP antibodies
      showed medium correlations to the RA patient's serum RF titer (r = 0.560, P <
      0.001) and disease activity (DAS28 score; r = 0.404, P < 0.001). Compared with
      the patients with low anti-CCP antibody titers (<100 RU/ml), patients with high
      anti-CCP antibody titers showed higher RF titers, worse DAS28 scores, and severe
      morning stiffness (P < 0.01). This study suggests that anti-CCP antibodies can be
      used for RA diagnosis and disease activity evaluation for northern Han Chinese
      patients. A combined diagnosis using both high titers of anti-CCP antibodies
      (>or=100 RU/ml) and a positive RF test markedly improves RA diagnostic
      specificity. Patients' DAS28 scores rise and morning stiffness intensifies with
      increasing anti-CCP antibody titers.

PMID- 20049503
TI  - Determinants of health care costs of HIV-positive patients in the Canary Islands,
      Spain.
AB  - The aims of this study were to estimate medical expenditures on human
      immunodeficiency virus (HIV) treatment and to identify significant associated
      variables. We performed a retrospective multi-centre study in the Canary Islands
      using a sample of 569 patients recruited at outpatient visits. The study examined
      demographic and clinical variables, health-related quality of life (HRQOL), and
      health care resources. Clinical data was obtained from medical records and
      patient interviews. Several empirical models for identifying the relationship
      between health care costs and independent variables were developed. The greatest
      expense came from pharmaceutical expenditure (82.1% of direct costs), while
      hospital costs only represented 4.6% of total expenditure. The data showed a
      statistically significant association between health care costs and the CD4 count
      of the previous year. HRQOL was also a significant variable. Therefore, CD4 cell
      count can be used to predict health care costs in patients. Policymakers could
      use this information to help guide their decisions in allocating limited health
      care resources to HIV treatments.

PMID- 20049504
TI  - Histone deacetylase controls adult stem cell aging by balancing the expression of
      polycomb genes and jumonji domain containing 3.
AB  - Aging is linked to loss of the self-renewal capacity of adult stem cells. Here,
      we observed that human multipotent stem cells (MSCs) underwent cellular
      senescence in vitro. Decreased expression of histone deacetylases (HDACs),
      followed by downregulation of polycomb group genes (PcGs), such as BMI1, EZH2 and
      SUZ12, and by upregulation of jumonji domain containing 3 (JMJD3), was observed
      in senescent MSCs. Similarly, HDAC inhibitors induced cellular senescence through
      downregulation of PcGs and upregulation of JMJD3. Regulation of PcGs was
      associated with HDAC inhibitor-induced hypophosphorylation of RB, which causes RB
      to bind to and decrease the transcriptional activity of E2F. JMJD3 expression
      regulation was dependant on histone acetylation status at its promoter regions. A
      histone acetyltransferase (HAT) inhibitor prevented replicative senescence of
      MSCs. These results suggest that HDAC activity might be important for MSC self
      renewal by balancing PcGs and JMJD3 expression, which govern cellular senescence
      by p16(INK4A) regulation.

PMID- 20049505
TI  - Lysozyme inhibitor conferring bacterial tolerance to invertebrate type lysozyme.
AB  - Invertebrate (I-) type lysozymes, like all other known lysozymes, are dedicated
      to the hydrolysis of peptidoglycan, the major bacterial cell wall polymer,
      thereby contributing to the innate immune system and/or digestive system of
      invertebrate organisms. Bacteria on the other hand have developed several
      protective strategies against lysozymes, including the production of periplasmic
      and/or membrane-bound lysozyme inhibitors. The latter have until now only been
      described for chicken (C-) type lysozymes. We here report the discovery,
      purification, identification and characterization of the first bacterial specific
      I-type lysozyme inhibitor from Aeromonas hydrophila, which we designate PliI
      (periplasmic lysozyme inhibitor of the I-type lysozyme). PliI has homologs in
      several proteobacterial genera and contributes to I-type lysozyme tolerance in A.
      hydrophila in the presence of an outer membrane permeabilizer. These and previous
      findings on C-type lysozyme inhibitors suggest that bacterial lysozyme inhibitors
      may have an important function, for example, in bacteria-host interactions.

PMID- 20049507
TI  - Intra-ocular expression of vascular endothelial growth factor (VEGF) and pigment
      epithelial-derived factor (PEDF) in a case of Eales' disease by
      immunohistochemical analysis: a case report.
AB  - We report a immunohistochemical study of expression of VEGF and PEDF in Eales'
      disease. An enucleated eye from a patient with Eales' disease and an age and sex
      matched donor eyeball were subjected to immunohistochemical and histopathological
      analysis to study the expression of VEGF and PEDF in the retinal region. Strong
      positive anti-VEGF immunostaining was found around the vessel walls in the retina
      in the eyeball from the Eales' disease patient compared with the donor control,
      from which it was almost absent. PEDF staining was detected in the normal donor
      eyeball retinal layers surrounding the blood vessels, and the photoreceptor and
      ganglion cell layer, whereas in the eyeball from Eales' disease patient PEDF
      staining was restricted to the surrounding blood vessels. The strong expression
      of VEGF in eyes with Eales' disease as opposed to weak expression of PEDF
      indicates the propensity of the disease to show neovascularization and recurrent
      hemorrhages.

PMID- 20049508
TI  - Successful treatment of choroidal neovascular membrane in retinitis pigmentosa
      with intravitreal bevacizumab.
AB  - We report a rare association of choroidal neovascularization (CNV) with retinitis
      pigmentosa and note its resolution by intravitreal injection of the anti-vascular
      endothelial growth factor (VEGF), bevacizumab. A classic choroidal neovascular
      membrane was seen in the right eye (RE) of a patient with sector retinitis
      pigmentosa. Bevacizumab 1.25 mg in 0.05 ml was injected intravitreally. The
      choroidal neovascular membrane was seen to regress following this single
      intravitreal bevacizumab injection with formation of a scar. CNV has very rarely
      been seen in association with retinitis pigmentosa. Anti-VEGF drugs have been
      shown to have a beneficial role in CNV with other causes; in this case their
      effectiveness in CNV associated with retinal dystrophies, for example retinitis
      pigmentosa, has been demonstrated.

PMID- 20049506
TI  - Correlates of viral richness in bats (order Chiroptera).
AB  - Historic and contemporary host ecology and evolutionary dynamics have profound
      impacts on viral diversity, virulence, and associated disease emergence. Bats
      have been recognized as reservoirs for several emerging viral pathogens, and are
      unique among mammals in their vagility, potential for long-distance dispersal,
      and often very large, colonial populations. We investigate the relative
      influences of host ecology and population genetic structure for predictions of
      viral richness in relevant reservoir species. We test the hypothesis that host
      geographic range area, distribution, population genetic structure, migratory
      behavior, International Union for Conservation of Nature and Natural Resources
      (IUCN) threat status, body mass, and colony size, are associated with known viral
      richness in bats. We analyze host traits and viral richness in a generalized
      linear regression model framework, and include a correction for sampling effort
      and phylogeny. We find evidence that sampling effort, IUCN status, and population
      genetic structure correlate with observed viral species richness in bats, and
      that these associations are independent of phylogeny. This study is an important
      first step in understanding the mechanisms that promote viral richness in
      reservoir species, and may aid in predicting the emergence of viral zoonoses from
      bats.

PMID- 20049509
TI  - Yersinia ironomics: comparison of iron transporters among Yersinia pestis
      biotypes and its nearest neighbor, Yersinia pseudotuberculosis.
AB  - Although Yersinia pestis epidemic biovars and Yersinia pseudotuberculosis are
      recently diverged, highly related species, they cause different diseases via
      disparate transmission routes. Since iron transport systems are important for
      iron acquisition from hosts and for survival in the environment, we have analyzed
      potential iron transport systems encoded by epidemic and non-epidemic or endemic
      strains of Y. pestis as well as two virulent Y. pseudotuberculosis strains.
      Computational biology analysis of these genomes showed a high degree of
      identity/similarity among 16 proven or possible iron/heme transporters
      identified. Of these, 7 systems were essentially the same in all seven genomes
      analyzed. The remaining 9 loci had 2-6 genetic variations among these genomes.
      Two untested, potential siderophore-dependent systems appear intact in Y.
      pseudotuberculosis but are disrupted or absent in all the endemic Y. pestis
      strains as well as the epidemic strains from the antiqua and mediaevalis biovars.
      Only one of these two loci are obviously disrupted in Y. pestis CO92 (epidemic
      orientalis biovar). Experimental studies failed to identify a role for hemin
      uptake systems in the virulence of pneumonic plague and suggest that Y. pestis
      CO92 does not make a siderophore other than Ybt.

PMID- 20049510
TI  - Bayesian model averaging for evaluation of candidate gene effects.
AB  - Statistical assessment of candidate gene effects can be viewed as a problem of
      variable selection and model comparison. Given a certain number of genes to be
      considered, many possible models may fit to the data well, each including a
      specific set of gene effects and possibly their interactions. The question arises
      as to which of these models is most plausible. Inference about candidate gene
      effects based on a specific model ignores uncertainty about model choice. Here, a
      Bayesian model averaging approach is proposed for evaluation of candidate gene
      effects. The method is implemented through simultaneous sampling of multiple
      models. By averaging over a set of competing models, the Bayesian model averaging
      approach incorporates model uncertainty into inferences about candidate gene
      effects. Features of the method are demonstrated using a simulated data set with
      ten candidate genes under consideration.

PMID- 20049511
TI  - Taxonomic boundaries, phylogenetic relationships and biogeography of the
      Drosophila willistoni subgroup (Diptera: Drosophilidae).
AB  - The Drosophila willistoni subgroup represents a complex with varying taxonomic
      levels. It encompasses D. willistoni and its five sibling species: D.
      equinoxialis, D. insularis, D. paulistorum, D. pavlovskiana and D. tropicalis. Of
      these, D. equinoxialis, D. tropicalis and D. willistoni present differentiation
      at subspecific level, whereas D. paulistorum represents a superspecies, formed by
      six semispecies. Despite this taxonomic and evolutionary complexity, many of
      these semi and subspecific taxa have not yet had their phylogenetic status tested
      in an explicitly molecular study. Aiming to contribute to the understanding of
      the evolution of this challenging group, we analyzed nucleotide sequences from
      two mitochondrial and four nuclear datasets, both individually and
      simultaneously, through different phylogenetic methods. High levels of
      incongruence were detected among partitions, especially concerning the
      mitochondrial sequences. As this incongruence was found to be statistically
      significant and robust to the use of different models and approaches, and
      basically restricted to mitochondrial loci, we suggest that it may stem mainly
      from hybridization-mediated asymmetrical introgression. Despite this, our nuclear
      data finally led to a phylogenetic hypothesis which further refines several
      aspects related to the willistoni subgroup phylogeny. In this respect, D.
      insularis, D. tropicalis, D. willistoni and D. equinoxialis successively branched
      off from the willistoni subgroup main stem, which recently subdivided to produce
      D. paulistorum and D. pavlovskiana. As regards the semispecies evolution, we
      found evidence of a recent diversification, which highly influenced the obtained
      results due to the associated small levels of genetic differentiation, further
      worsened by the possibly associated incompletely sorted ancestral polymorphisms
      and by the possibility of introgression. This study also raises the question of
      whether these semispecies are monophyletic at all. This reasoning is particularly
      interesting when one considers that similar levels of reproductive isolation
      could be attained through infection with different Wolbachia strains.

PMID- 20049512
TI  - Characterization of a para-nitrophenol catabolic cluster in Pseudomonas sp.
      strain NyZ402 and construction of an engineered strain capable of simultaneously
      mineralizing both para- and ortho-nitrophenols.
AB  - Pseudomonas sp. strain NyZ402 was isolated for its ability to grow on para
      nitrophenol (PNP) as a sole source of carbon, nitrogen, and energy, and was shown
      to degrade PNP via an oxidization pathway. This strain was also capable of
      growing on hydroquinone or catechol. A 15, 818 bp DNA fragment extending from a
      800-bp DNA fragment of hydroxyquinol 1,2-dioxygenase gene (pnpG) was obtained by
      genome walking. Sequence analysis indicated that the PNP catabolic gene cluster
      (pnpABCDEFG) in this fragment shared significant similarities with a recently
      reported gene cluster responsible for PNP degradation from Pseudomonas sp. strain
      WBC-3. PnpA is PNP 4-monooxygenase converting PNP to hydroquinone via
      benzoquinone in the presence of NADPH, and genetic analysis indicated that pnpA
      plays a key role in PNP degradation. pnpA1 present in the upstream of the cluster
      (absent in the cluster from strain WBC-3) encodes a protein sharing as high as
      55% identity with PnpA, but was not involved in PNP degradation by either in
      vitro or in vivo analyses. Furthermore, an engineered strain capable of growing
      on PNP and ortho-nitrophenol (ONP) was constructed by introducing onpAB (encoding
      ONP monooxygenase and ortho-benzoquinone reductase which catalyzed the
      transformation of ONP to catechol) from Alcaligenes sp. strain NyZ215 into strain
      NyZ402.

PMID- 20049513
TI  - Protease inhibitor SERPINA1 expression in epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is the most lethal gynecologic cancer with a 5 years
      survival rate of 30-40% in patients diagnosed with high-grade invasive disease
      (TOV). This is in stark contrast to the 95% 5 years survival rate in ovarian
      cancer patients diagnosed with low malignant potential (LMP) disease. The
      progression from localized tumor to invasive metastasis involves matrix
      proteolysis. Protease inhibitors are thought to play a key role by limiting this
      process. Using the Affymetrix HG-U133A GeneChip array, we have studied all serine
      protease inhibitors and found several serpin family members that are
      differentially expressed between LMP and TOV serous tumors. SERPINA1 was selected
      for further study due to its high expression in the majority of LMP tumors and
      its low expression in TOV tumors; observations that were also validated by
      quantitative-PCR (Q-PCR). To study the effects of its over expression on
      different tumorigenic parameters, SERPINA1 was cloned in the pcDNA3.1+ plasmid
      which was subsequently used to derive stable clones from two invasive ovarian
      cancer cell lines, TOV-112D and TOV-1946. We found no effect of SERPINA1 over
      expression on tumor growth in SCID mice although cell migration and invasion were
      affected in in vitro assays. There was also no association between patient
      survival and SERPINA1 immunostaining, however, SERPINA1 localization was
      different in LMP (nuclear) and TOV (cytoplasmic) tumors. SERPINA1 remains an
      interesting candidate since protein homeostasis, regulated by proteases and their
      inhibitors, should be studied holistically in order to assess their full impact
      in tumor progression.

PMID- 20049514
TI  - Protective effects of the volatile oil of Nigella sativa seeds on beta-cell
      damage in streptozotocin-induced diabetic rats: a light and electron microscopic
      study.
AB  - The aim of this study was to evaluate the possible protective effects of the
      volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and
      ultrastructural changes of pancreatic beta-cells in STZ-induced diabetic rats.
      STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce
      diabetes. The rats in NS treated groups were given NS (0.2 ml/kg) once a day
      orally for 4 weeks starting 3 days prior to STZ injection. To date, no
      ultrastructural changes of pancreatic beta-cells in STZ induced diabetic rats by
      NS treatment have been reported. Islet cell degeneration and weak insulin
      immunohistochemical staining was observed in rats with STZ-induced diabetes.
      Increased intensity of staining for insulin, and preservation of beta-cell
      numbers were apparent in the NS-treated diabetic rats. The protective effect of
      NS on STZ-diabetic rats was evident by a moderate increase in the lowered
      secretory vesicles with granules and also slight destruction with loss of cristae
      within the mitochondria of beta-cell when compared to control rats. These
      findings suggest that NS treatment exerts a therapeutic protective effect in
      diabetes by decreasing morphological changes and preserving pancreatic beta-cell
      integrity. Consequently, NS may be clinically useful for protecting beta-cells
      against oxidative stress.

PMID- 20049515
TI  - An ensemble classifier of support vector machines used to predict protein
      structural classes by fusing auto covariance and pseudo-amino acid composition.
AB  - The purpose of this article is to identify protein structural classes by using
      support vector machine (SVM) ensemble classifier, which is very efficient in
      enhancing prediction performance. Firstly, auto covariance (AC) and pseudo-amino
      acid composition (PseAAC) were used in protein representation. AC focuses on
      adjacent effects and PseAA composition takes sequence order patterns into
      account. Secondly, SVMs were trained on the datasets represented by different
      descriptors. The last, ensemble classifier, which constructed on the individual
      classifiers through a voting strategy, gave the final prediction results.
      Meanwhile, very promising prediction accuracy 93.14% was obtained by Jackknife
      test. The experimental results showed that the ensemble system can improve the
      prediction performance greatly and generate more stable and safer predictors. The
      current method featured by fusing the protein primary sequence information
      transferred by AC and described by protein PseAA composition may play an
      important complementary role in other related applications.

PMID- 20049516
TI  - Investigating the function of three non-synonymous SNPs in EGFR gene: structural
      modelling and association with breast cancer.
AB  - Non-synonymous single nucleotide polymorphisms (nsSNPs) represent common genomic
      variations that alter protein sequence and function. Some nsSNPs affecting
      conserved amino acids have been reported to be associated with cancer
      susceptibility. Interestingly, Epidermal Growth Factor Receptor (EGFR) is
      commonly overexpressed and mutated in many cancers. In this study, we
      investigated the structural effect of three deleterious nsSNPs: rs17337451
      (R962G), rs1140476 (R977C) and rs17290699 (H988P) within EGFR using computational
      tools. The modelled mutant dimers showed less stability than wild type EGFR
      dimer. Furthermore, we showed the important role of R962 and H988 residues in the
      EGFR dimer formation. We also report preliminary experimental data for SNP R977C
      suggesting that the variant C977 might confer greater risk for breast cancer.
      These results contribute to an improved understanding of the EGFR dimer stability
      and provide new elements for understanding the relationship between EGFR and
      cancer.

PMID- 20049517
TI  - Heterogeneous properties of individual molecules of beta-galactosidase from the
      thermophilic bacteria Geobacillus stearothermophilus.
AB  - Single enzyme molecule assays were performed on beta-galactosidase from the
      thermophilic bacteria Geobacillus stearothermophilus using a capillary
      electrophoresis-based continuous flow assay and the substrate DDAO-beta-D: 
      galactoside. The enzyme was found to be heterogeneous with respect to catalytic
      rate, electrophoretic mobility and activation energy of catalysis. Catalytic rate
      was also found to vary over time for individual molecules at elevated
      temperature. Comparison with beta-galactosidase from the mesophilic bacteria
      Escherichia coli showed that the variation in activity over time was less
      pronounced and the average activation energy of catalysis was lower for the
      Geobacillus stearothermophilus enzyme. Attempts to measure the properties of
      individual beta-galactosidase molecules from the thermophilic bacteria Thermus
      thermophilus and the cold-adapted bacteria Pseudoalteromas haloplanktis using
      this assay were unsuccessful.

PMID- 20049518
TI  - Explaining Mendelian inheritance in genetic consultations: an IPR study of
      counselor and counselee experiences.
AB  - The explanation of Mendelian inheritance is a key component of most genetic
      counselling consultations, yet no evidence base exists for this area of practice.
      This qualitative study used Interpersonal Process Recall (IPR) to explore how
      information about X-linked inheritance is provided and received in genetic
      counseling. Twelve consultations involving two senior genetic counselors and 21
      counselees were videotaped. Section(s) of videotape featuring the explanation
      were subsequently played back separately to both counselees and counselors and
      their responses and reflections recorded. All interviews were fully transcribed
      and analysed using the constant comparison method. A personalized diagram, drawn
      "live" by the counselor during the consultation was recalled by counselees as
      being central to their understanding of the "bottom line". This helped bridge the
      gap between scientific information and their family experience and did not appear
      to require a baseline understanding of genetic concepts such as genes or
      chromosomes. Counselors reflected on the diagram's positive impact on the way
      they sequenced, paced and tailored the explanation. A positive counselor
      counselee relationship was vital even during this educative exchange: for
      counselees to feel at ease discussing complex genetic information and to help
      gauge counselee understanding.

PMID- 20049520
TI  - Factors determining prenatal HIV testing for prevention of mother to child
      transmission of HIV in Mpumalanga, South Africa.
AB  - This study assessed factors associated with participation in HIV counseling and
      testing and reported reasons for not taking part in Voluntary HIV Counseling and
      Testing among 930 pregnant women attending clinics for antenatal care in South
      Africa. Results indicate that from 930 clients interviewed 87% had agreed to
      participate in individual pre-test HIV counseling and 81.2% had received their
      test results in post-test counseling. Fear for taking the test, lack of
      confidentiality and knowing one's HIV status were the main reasons why women
      refused to test. In multivariable analysis trust of HCT provider was associated
      with participation in HIV pre-test counseling and no risky drinking was
      associated with participation in HIV post-test counseling. These findings suggest
      mistrust towards HCT providers should be reduced and screening and brief
      intervention for alcohol problems provided.

PMID- 20049521
TI  - Risky sex- and drug-seeking in a probability sample of men-for-men online
      bulletin board postings.
AB  - There has been limited research on men who have sex with men's postings in online
      sex-seeking bulletin boards. This study uses a probability sample of 1,438
      advertisements ostensibly posted by men-seeking-men in the New York City section
      of Craigslist.org. Ad's qualitative text were coded for various sex- and drug
      seeking behaviors. The proportion of ads seeking unprotected/uninhibited sex
      (3.0%) and party-n-play (i.e., sex/drug) encounters (4.2%) was low. In contrast,
      12.7% of postings specified safe sex encounters, and 17.5% of postings specified
      that they were "drug and disease free." Prevalence of certain behaviors varied by
      time that ads were posted. Implications for health/community service providers
      are discussed.

PMID- 20049519
TI  - Agreement of self-reported and genital measures of sexual arousal in men and
      women: a meta-analysis.
AB  - The assessment of sexual arousal in men and women informs theoretical studies of
      human sexuality and provides a method to assess and evaluate the treatment of
      sexual dysfunctions and paraphilias. Understanding measures of arousal is,
      therefore, paramount to further theoretical and practical advances in the study
      of human sexuality. In this meta-analysis, we review research to quantify the
      extent of agreement between self-reported and genital measures of sexual arousal,
      to determine if there is a gender difference in this agreement, and to identify
      theoretical and methodological moderators of subjective-genital agreement. We
      identified 132 peer- or academically-reviewed laboratory studies published
      between 1969 and 2007 reporting a correlation between self-reported and genital
      measures of sexual arousal, with total sample sizes of 2,505 women and 1,918 men.
      There was a statistically significant gender difference in the agreement between
      self-reported and genital measures, with men (r = .66) showing a greater degree
      of agreement than women (r = .26). Two methodological moderators of the gender
      difference in subjective-genital agreement were identified: stimulus variability
      and timing of the assessment of self-reported sexual arousal. The results have
      implications for assessment of sexual arousal, the nature of gender differences
      in sexual arousal, and models of sexual response.

PMID- 20049522
TI  - Acceptability of a non-woven device for vaginal drug delivery of microbicides or
      other active agents.
AB  - Vaginal microbicides could reduce incidence of HIV. However, the current method
      of delivering gel formulations (standard applicator) can result in acceptability
      concerns/issues. This study evaluated the concept of using a non-woven textile
      material (modified tampon) for vaginal drug delivery. The study was nested within
      a Phase I randomized safety trial of lime juice concentrations used intra
      vaginally. Of 47 women completing the safety trial, 16 were interviewed about
      their experiences. Overall, women found the concept of non-woven materials for
      vaginal drug delivery acceptable for use in delivering yeast medications (13 of
      16) and STI/HIV preventives (10 of 16).

PMID- 20049523
TI  - Identifying unmet mental health needs in children of formerly homeless mothers
      living in a supportive housing community sector of care.
AB  - This study reports psychosocial characteristics of a sample of 111 children (K to
      2nd grade) and their mothers who were living in urban supportive housings. The
      aim of this study was to document the various types and degree of risk endemic to
      this population. First, we describe the psychosocial characteristics of this
      homeless sample. Second, we compared this homeless sample with a grade-matched,
      high-risk, school-based sample of children (n = 146) who were identified as
      showing early symptoms of disruptive behaviors. Third, we compared the parents in
      both samples on mental health, parenting practices, and service utilization.
      Results showed that children living in supportive housing were in the at-risk
      range and had comparable levels of externalizing problems, internalizing
      problems, school problems and emotional strengths with the school-based risk
      sample receiving prevention services at a family support community agency.
      Mothers in supportive housing reported significantly higher psychological
      distress, less optimal parenting practices and greater service utilization. These
      findings are among the first to provide empirical support for the need to deliver
      prevention interventions in community sectors of care.

PMID- 20049524
TI  - XRCC3 5'-UTR and IVS5-14 polymorphisms and breast cancer susceptibility: a meta
      analysis.
AB  - Published data on the association between XRCC3 5'-UTR and IVS5-14 polymorphisms
      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 these polymorphisms
      and breast cancer risk. The pooled ORs were performed for codominant model,
      dominant model, and recessive model, respectively. A total of four studies were
      involved in the meta-analysis with 6,303 cases and 6,563 controls for XRCC3 5'
      UTR polymorphism and with 6,270 cases and 6,682 controls for XRCC3 IVS5-14
      polymorphism. For XRCC3 5'-UTR A/G polymorphism, significantly elevated breast
      cancer risk was associated with variant genotype when all studies were pooled
      into the meta-analysis (AG vs. AA: OR = 1.11, 95% CI = 1.03-1.19; dominant model:
      OR = 1.09, 95% CI = 1.01-1.17). For XRCC3 IVS5-14 A/G polymorphism, significantly
      decreased breast cancer risk was associated with variant genotype (GG vs. AA: OR
      = 0.86, 95% CI = 0.77-0.96). In conclusion, this meta-analysis suggests that the
      variant G allele of XRCC3 5'-UTR polymorphism is a low-penetrant risk factor for
      developing breast cancer, while the variant G allele of XRCC3 IVS5-14
      polymorphism has a protective effect on breast cancer development.

PMID- 20049525
TI  - In vitro activity of antimicrobial agents against Legionella isolated from
      environmental water systems: first results from Turkey.
AB  - We evaluated the in vitro activity of antimicrobial agents against Legionella
      obtained from hotel and hospital water systems in three different regions of
      Turkey. Sixty-five Legionella strains (Legionella pneumophila serogroup 6 [n=32],
      L. pneumophila serogroup 1 [n=27], L. pneumophila serogroup 3 [n=2], and
      Legionella spp. [n=4]) were tested against levofloxacin, ciprofloxacin,
      clarithromycin, azithromycin, and rifampicin. The minimum inhibitory
      concentration (MIC) values of each antimicrobial agent for these strains was
      determined by the microdilution method using buffered yeast extract medium
      supplemented with 0.1% ketoglutarate broth. L. pneumophila ATCC 33152,
      Staphylococcus aureus ATCC 29213, and Escherichia coli ATCC 25922 were used as
      controls. Minimum inhibitory concentration values were in the following ranges:
      clarithromycin 0.001-0.5 mg/L, azithromycin 0.001-0.5 mg/L, levofloxacin 0.001
      0.5 mg/L, ciprofloxacin 0.001-0.125 mg/L, and rifampicin 0.001- 0.5 mg/L. The
      MIC(90) for rifampicin, levofloxacin, ciprofloxacin, azithromycin, and
      clarithromycin were 0.015, 0.125, 0.06, 0.125, and 0.06 mg/L, respectively. To
      the best of our knowledge, this is the first study to determine in vitro
      activities of antimicrobial agents against Legionella species in Turkey.
      Rifampicin had the lowest MIC(90) value. It would seem that azithromycin and
      clarithromycin exhibit good activity as well as levofloxacin and ciprofloxacin
      against Legionella isolated from environmental water systems in Turkey.

PMID- 20049526
TI  - QPCR: a tool for analysis of mitochondrial and nuclear DNA damage in
      ecotoxicology.
AB  - The quantitative PCR (QPCR) assay for DNA damage and repair has been used
      extensively in laboratory species. More recently, it has been adapted to
      ecological settings. The purpose of this article is to provide a detailed
      methodological guide that will facilitate its adaptation to additional species,
      highlight its potential for ecotoxicological and biomonitoring work, and
      critically review the strengths and limitations of this assay. Major strengths of
      the assay include very low (nanogram to picogram) amounts of input DNA; direct
      comparison of damage and repair in the nuclear and mitochondrial genomes, and
      different parts of the nuclear genome; detection of a wide range of types of DNA
      damage; very good reproducibility and quantification; applicability to properly
      preserved frozen samples; simultaneous monitoring of relative mitochondrial
      genome copy number; and easy adaptation to most species. Potential limitations
      include the limit of detection (approximately 1 lesion per 10(5) bases); the
      inability to distinguish different types of DNA damage; and the need to base
      quantification of damage on a control or reference sample. I suggest that the
      QPCR assay is particularly powerful for some ecotoxicological studies.

PMID- 20049527
TI  - Tau phosphorylation and cleavage in ethanol-induced neurodegeneration in the
      developing mouse brain.
AB  - Previous studies indicated that ethanol-induced neurodegeneration in postnatal
      day 7 (P7) mice, widely used as a model for the fetal alcohol spectrum disorders,
      was accompanied by glycogen synthase kinase-3beta (GSK-3beta) and caspase-3
      activation. Presently, we examined whether tau, a microtubule associated protein,
      is modified by GSK-3beta and caspase-3 in ethanol-treated P7 mouse forebrains. We
      found that ethanol increased phosphorylated tau recognized by the paired helical
      filament (PHF)-1 antibody and by the antibody against tau phosphorylated at
      Ser199. Ethanol also generated tau fragments recognized by an antibody against
      caspase-cleaved tau (C-tau). C-tau was localized in neurons bearing activated
      caspase-3 and fragmented nuclei. Over time, cell debris and degenerated
      projections containing C-tau appeared to be engulfed by activated microglia. A
      caspase-3 inhibitor partially blocked C-tau formation. Lithium, a GSK-3beta
      inhibitor, blocked ethanol-induced caspase-3 activation, phosphorylated tau
      elevation, C-tau formation, and microglial activation. These results indicate
      that tau is phosphorylated by GSK-3beta and cleaved by caspase-3 during ethanol
      induced neurodegeneration in the developing brain.

PMID- 20049528
TI  - Disease severity in sibling pairs with type 1 Gaucher disease.
AB  - The only prognostic markers in Gaucher disease, the most common lysosomal storage
      disorder, are young age at first symptom/sign and the presence of null/severe
      mutations, both being predictive of more severe phenotypes. Therefore, it would
      be helpful to know whether siblings with the same genotype can be expected to
      experience comparable phenotypic expression. All non-neuronopathic sibling pairs
      in our referral clinic (1993-2008) with the same genotype were included. For each
      pair, gender, date of birth, severity score index at presentation, age at
      diagnosis and first symptom/sign, presence of bone involvement, spleen status,
      and use of enzyme replacement therapy were tabulated. There were 90 pairs of
      siblings: two sets of identical twins; 24 pairs of brothers, 24 pairs of sisters,
      and 42 pairs of mixed gender. For all measures of disease severity used, only in
      sibling pairs with an older sister and a younger brother were phenotypes
      significantly different between siblings. Thus, this large cohort of sibling
      pairs with type 1 Gaucher disease confirmed that, in general, the phenotypic
      expression in the younger sibling will be similar enough to that of an older
      affected sibling that genetic counseling may use those findings in a prognostic
      way.

PMID- 20049529
TI  - Tumoral calcinosis.

PMID- 20049531
TI  - Pediatric Gaucher disease type I and mild growth hormone deficiency: a new
      feature?
AB  - A 5-year-old girl was referred to the Department of Pediatrics and Neonatology,
      Guglielmo da Saliceto Hospital, Italy, because of growth retardation. Clinical
      and laboratory investigations showed pallor, hepatosplenomegaly, anemia and
      low/normal platelet count. Further investigations led to the diagnosis of Gaucher
      disease (GD). We believe this is the first report of growth hormone deficiency in
      a growth-retarded child with GD. After 1 year of imiglucerase replacement enzyme
      therapy, her bone age had normalized, linear growth rate had accelerated, and
      insulin growth factor-1 (IGF-1) and, perhaps more interestingly, growth hormone
      deficiency, had normalized. While the pathophysiological mechanisms underlying
      compromised growth in GD are poorly understood, the response to imiglucerase
      reported in this patient suggests that growth hormone deficiency is related to
      the underlying metabolic disorder in GD, rather than a primary endocrine
      pathology. Growth hormone deficiency adds to an already extensive list of
      possible clinical manifestations of this heterogeneous and complex disorder.

PMID- 20049530
TI  - Abnormal nonstoring capillary endothelium: a novel feature of Gaucher disease.
      Ultrastructural study of dermal capillaries.
AB  - Ultrastructural study of skin biopsies in two cases of Gaucher disease (GD)
      patients (types II and III) revealed hitherto unknown alteration of the blood
      capillary endothelial cells (ECs) featured by hypertrophy and numerous
      subplasmalemmal microvesicles underneath both the apical and basal membranes.
      There was also prominent apical membrane folding with formation of filiform and
      large cytoplasmic projections, with occasional transcapillary cytoplasmic
      bridges. Similar, though less frequently expressed, changes were manifested at
      the basal membrane by numerous cytoplasmic projections into the subendothelial
      space. Regressive changes with EC breakdown were rare. Lysosomal storage was
      always absent. Besides EC hypertrophy, there was also increased EC density in the
      capillary lumen, leading to pronounced changes in capillary architecture with
      loose or incomplete EC anchoring. There were also signs of EC sprouting. Some
      pericytes displayed an increase in size and number of cytoplasmic processes,
      which often extended into distant pericapillary regions. The spectrum of changes
      suggests that a significant positive growth effect on EC occurs in GD. The
      putative mechanisms triggered by GBA1 deficiency leading to EC involvement are
      discussed. The authors are well aware of the fact the results, based on a
      nontraditional type of bioptic samples, are preliminary, but they are worth
      following, as further ultrastructural and functional studies of blood endothelium
      in GD may open a novel field in molecular cell pathophysiology of the disorder:
      endothelial dysfunction.

PMID- 20049532
TI  - Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with
      abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5'
      phosphate availability.
AB  - We describe two neonates presenting with perinatal hypophosphatasia and severe
      epileptic encephalopathy resulting in death. Both had increased levels of urinary
      vanillactate, indicating functional deficiency of aromatic amino acid
      decarboxylase, a pyridoxal-5-phosphate (PLP)-dependent enzyme required for
      dopamine and serotonin biosynthesis. Clinical findings and results of subsequent
      metabolic investigations were consistent with secondary pyridoxine-deficient
      encephalopathy. These patients highlight the importance of tissue non-specific
      alkaline phosphatase in the neuronal PLP-dependent metabolism of
      neurotransmitters. In addition, the disturbance of PLP metabolism appears to
      underlie the predominant neurological presentation in our patients. We recommend
      the measurement of serum alkaline phosphatase (ALP) during the assessment of
      perinatal seizures. 

PMID- 20049533
TI  - Study of inborn errors of metabolism in urine from patients with unexplained
      mental retardation.
AB  - Mental retardation (MR) is a common disorder frequently of unknown origin.
      Because there are few studies regarding MR and inborn errors of metabolism (IEM),
      we aimed to identify patients with IEM from a cohort of 944 patients with
      unexplained MR. Biochemical examinations such as determination of creatine (Cr)
      metabolites, acylcarnitines, purine, and pyrimidines in urine were applied. We
      found seven patients with IEM [three with cerebral Cr deficiency syndromes
      (CCDS)], one with adenylosuccinate lyase (ADSL) deficiency, and three, born
      before the neonatal metabolic screening program in Catalonia, with
      phenylketonuria (PKU). All told, they represent 0.8% of the whole cohort. All of
      them had additional symptoms such as epilepsy, movement disorders, autism, and
      other psychiatric disturbances. In conclusion, in patients with MR, it is
      essential to perform a thorough appraisal of the associated signs and symptoms,
      and in most disorders, it is necessary to apply specific analyses. In some cases,
      it is important to achieve an early diagnosis and therapy, which may reduce the
      morbimortality, and to offer genetic counselling.

PMID- 20049534
TI  - Fatty acid oxidation disorders: outcome and long-term prognosis.
AB  - Assessing the outcome of fatty acid oxidation disorders is difficult, as most are
      rare. For diagnosis by newborn screening, the situation is compounded: far more
      cases are diagnosed by screening than by clinical presentation, representing a
      somewhat different cohort. The literature on outcome was reviewed. For disorders
      other than medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency
      there was insufficient evidence to make many firm statements. In MCAD deficiency,
      risk of death in the first 72 h is around 4%, with a further approximately 5-7%
      fatality rate in the first 6 years but very low subsequent risk in previously
      undiagnosed patients. The risk of death after diagnosis is very low at any age,
      with good management. The long-term outcome is good nowadays. Very-long-chain
      acyl-CoA dehydrogenase deficiency poses a risk of death in early infancy, but the
      condition is generally treatable, with a good outcome after diagnosis.
      Approximately 10-20% of patients diagnosed by newborn screening and treated
      nevertheless suffer episodic rhabdomyolysis. Some patients never become
      symptomatic. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is
      treatable, but most patients suffer episodic hypoketotic hypoglycaemia and
      rhabdomyolysis. Generalised mitochondrial tri-functional protein deficiency has
      high early mortality rate. A more insidious presentation also occurs, with
      symptoms sometimes confined to progressive axonal neuropathy. Among carnitine
      cycle disorders, carnitine transporter deficiency, potentially lethal, is
      uniformly successfully treated orally with carnitine. Carnitine-acylcarnitine
      translocase and early-onset carnitine palmitoyl transferase type II (CPT II)
      deficiencies have an extremely high neonatal mortality rate. Late-onset CPT II is
      characterised only by episodic rhabdomyolysis on severe exercise. CPT type IA
      deficiency may often be benign, although early presentation with hypoketotic
      hypoglycaemia certainly occurs.

PMID- 20049535
TI  - Acute eosinophilic endomyocarditis: early diagnosis and localisation of the
      lesion by cardiac magnetic resonance imaging.
AB  - Cardiac involvement is the main cause of morbidity and mortality in
      hypereosinophilic syndrome. In a patient with hypereosinophilia and a normal
      echocardiography, cardiac magnetic resonance imaging (CMR) helped confirm early
      cardiac involvement by demonstrating a typical pattern of left ventricular
      subendocardial and papillary muscle involvement. The use of CMR facilitated
      prompt institution of aggressive therapy and was useful in monitoring response to
      treatment.

PMID- 20049536
TI  - Prognostic value of late gadolinium enhancement in hypertensive patients with
      known or suspected coronary artery disease.
AB  - To determine the prognosis of a myocardial scar assessed by a late gadolinium
      enhancement (LGE) technique of cardiac magnetic resonance (CMR) in hypertensive
      patients with known or suspected coronary artery disease (CAD). Patients with
      systemic hypertension with known or suspected CAD without a clinical history of
      myocardial infarction were enrolled. All patients underwent CMR for assessment of
      cardiac function and LGE. Prognostic data was determined by the occurrence of a
      hard cardiac endpoint, defined as cardiac death or a non-fatal myocardial
      infarction, or major adverse cardiac events (MACEs), defined as cardiac death, a
      non-fatal myocardial infarction, or hospitalization due to heart failure,
      unstable angina, or life-threatening ventricular arrhythmia. A total of 1,644
      patients were enrolled; 48% were males and the mean age was 65 +/- 11 years. The
      average follow-up time was 863 +/- 559 days. Four hundred fifty-three (28%)
      patients had LGE. LGE was the strongest and most independent predictor for hard
      events and MACEs with hazard ratios of 4.77 and 3.38, respectively. Other
      independent predictors of hard events and MACEs were left ventricular ejection
      fraction and mass, the use of a beta-blocker, and a history of heart failure. The
      risk of cardiac events increased as the extent of LGE increased; the hazard ratio
      was 12.74 for hard events for those with a LGE >20% of the myocardium. LGE is the
      most important and independent predictor for cardiac events in hypertensive
      patients with known or suspected CAD.

PMID- 20049537
TI  - Comparison of dual-source CT coronary angiography and conventional coronary
      angiography for detecting coronary artery disease.
AB  - To evaluate the diagnostic accuracy of dual-source CT coronary angiography for
      detecting coronary artery stenosis. From February 2008 to January 2009, dual
      source CT coronary CT angiography (DSCT-CCTA) and conventional coronary
      angiography (CAG) were both performed in 84 patients who had either clinical
      symptoms or a high risk of coronary artery disease. The diagnostic accuracy of
      DSCT-CCTA was evaluated by comparing it with that of CAG, which was regarded as
      the gold standard for making the diagnosis of coronary artery disease. Occlusion
      or stenosis of various degrees was revealed by DSCT-CCTA in 244 segments of 84
      patients. Compared to CAG, segment-based sensitivity, specificity, positive
      predictive value and negative predictive value of DSCT-CCTA were 97.4, 97.8, 92.2
      and 100%, respectively. The diagnostic accuracy of DSCT-CCTA for the detection of
      coronary artery stenosis was 96.5%. The paired chi2 tests revealed no significant
      difference between DSCT-CCTA and CAG for making the diagnosis of coronary artery
      disease (P = 0.076). The diagnostic performance of DSCT-CCTA is generally as
      accurate as that of CAG. Thus, DSCT-CCTA is a reliable non-invasive method for
      detecting coronary artery stenosis.

PMID- 20049538
TI  - The ethics of health barriers to immigration: morality among neighbours.
AB  - Many countries encourage immigration, yet almost without exception they impose
      medical conditions on the admissibility of prospective immigrants. This paper
      examines the ethical defensibility of this practice. It argues that the
      neighbourhood principle, which states that we owe a greater duty to neighbours
      than to strangers, when properly understood, extends to all human beings, that
      economic and safety considerations play only a limited role in ethically
      underwriting an exclusionary policy, and that medical immigration criteria should
      be harmonized with treatment eligibility criteria for citizens of the relevant
      countries themselves.

PMID- 20049539
TI  - Characterization of proteins with wide-angle X-ray solution scattering (WAXS).
AB  - X-ray solution scattering in both the small-angle (SAXS) and wide-angle (WAXS)
      regimes is making an increasing impact on our understanding of biomolecular
      complexes. The accurate calculation of WAXS patterns from atomic coordinates has
      positioned the approach for rapid growth and integration with existing Structural
      Genomics efforts. WAXS data are sensitive to small structural changes in
      proteins; useful for calculation of the pair-distribution function at relatively
      high resolution; provides a means to characterize the breadth of the structural
      ensemble in solution; and can be used to identify proteins with similar folds.
      WAXS data are often used to test structural models, identify structural
      similarities and characterize structural changes. WAXS is highly complementary to
      crystallography and NMR. It holds great potential for the testing of structural
      models of proteins; identification of proteins that may exhibit novel folds;
      characterization of unfolded or natively disordered proteins; and detection of
      structural changes associated with protein function.

PMID- 20049540
TI  - Hydrogen peroxide in upper gastrointestinal bleeding: a coming of age?

PMID- 20049541
TI  - Hepatitis vaccination of men who have sex with men at gay pride events.
AB  - Prevention researchers have advocated primary prevention such as vaccination in
      alternative venues. However, there have been major questions about both the
      attendance of, and the ability to, vaccinate high-risk individuals in such
      settings. The current study seeks to assess the feasibility of vaccinating high
      risk men who have sex with men (MSM) at Gay Pride events. The research questions
      are: Do gay men who are sampled at Gay Pride events engage in more or less risky
      behavior than gay men sampled at other venues? Do the gay men who receive
      hepatitis vaccinations at Gay Pride engage in more or less risky behavior than
      gay men at Gay Pride who do not receive hepatitis vaccination? Of the 3689 MSM
      that completed the Field Risk Assessment (FRA), 1095/3689 = 29.68% were recruited
      at either the 2006 or 2007 Long Beach, California Gay Pride events. The
      remaining, 2594/3689 = 70.32% were recruited at Long Beach gay bars, gay
      community organizations and institutions, and through street recruitment in
      various gay enclaves in the Long Beach area. Logistic regression analysis yielded
      eight factors that were associated with non-attendance of Gay Pride: Age, had sex
      while high in the last 12 months, had unprotected anal intercourse (UAI) in the
      last 12 months, had sex for drugs/money in the last 12 months, been diagnosed
      with a sexually transmitted infection (STI) in the last 12 months, used nitrites
      (poppers) in the last 12 months, and used methamphetamine in the last 12 months.
      Identifying as White, Asian, or African American compared to Hispanic was also
      associated with non-attendance. Bivariate analysis indicated that, of the MSM
      sampled at Gay Pride, 280/1095 = 25.57% received a hepatitis vaccination there.
      The MSM sampled at Gay Pride who reported engaging in UAI or having used any
      stimulant (cocaine, crack-cocaine, or methamphetamine) in the last 12 months were
      more likely to receive hepatitis vaccination on-site. The results provide
      evidence for the viability of successfully vaccinating high-risk MSM at Gay Pride
      events. However, it is vital that no-cost vaccinations are also funded in other
      community settings such as STI clinics, drug treatment programs, prisons,
      universities, and other community resource centers in order to reach those
      additional high-risk MSM who do not attend Gay Pride.

PMID- 20049543
TI  - Acquisition parameters for oncologic imaging with a new SPECT/multislice CT
      scanner.
AB  - INTRODUCTION: Single photon emission computed tomography/computed tomography
      (SPECT/CT) delivers in a single imaging modality the functional-metabolic
      information from the SPECT image, combined with the detailed anatomical
      information from a diagnostic quality CT scanner. METHOD: In this review, we
      provide the details for the acquisition, processing, and display of the SPECT, as
      well as the CT, and the fused SPECT/CT images, with one of the newest devices
      that combines a dual-headed gamma camera with a multislice CT scanner. Also, we
      go over the performance characteristics, including the planning and installation
      requirements for this type of scanners. In addition, we describe what are the
      current and feasible near-future applications of this new and exciting hybrid
      imaging modality. DISCUSSION: The ability to combine an optimized state-of-the
      art SPECT image, with resolutions down to 5 mm, with a diagnostic quality CT
      image-using slices as thin as 1.25 mm-provides a diagnostic advantage that
      potentially can deliver a more convenient and faster diagnosis, with clinical
      implications in a significant percentage of patients. This imaging technique has
      been investigated in a wide range of studies for the oncologic patient, including
      but not limited to bone scintigraphy, (111)In-pentetreotide scintigraphy,
      lymphoscintigraphy, (67)Ga and labeled leukocyte infection imaging, (131)I
      metaiodobenzylguanidine, parathyroid scintigraphy, (131)I diagnostic
      scintigraphy, and (111)In ProstaScint, and for planning of radionuclide therapy.
      CONCLUSION: Therefore, this evolving and exciting imaging modality will continue
      to grow and define its place as an integral part of the evaluation of the cancer
      patient.

PMID- 20049544
TI  - Homogenization of an electrophysiological model for a strand of cardiac myocytes
      with gap-junctional and electric-field coupling.
AB  - We derive a homogenized description of the electrical communication along a
      single strand of myocytes in the presence of gap-junctional and electric-field
      coupling. In the model, cells are electrically coupled through narrow clefts that
      are resistively connected to extracellular space. Cells are also coupled directly
      through gap junctions. We perform numerical simulations of this full model and
      its homogenization. We observe that the full and homogenized descriptions agree
      when gap-junctional coupling is at physiologically normal levels. When gap
      junctional coupling is low, the two descriptions disagree. In this case, only the
      full model captures the behavior that the ephaptic mechanism can speed up action
      potential propagation. A strength of our homogenized description is that it is a
      macroscale model that can account for the preferential localization of Na+
      channels at the ends of cells.

PMID- 20049545
TI  - Properties of the proximate parameter tuning regularization algorithm.
AB  - An important aspect of systems biology research is the so-called "reverse
      engineering" of cellular metabolic dynamics from measured input-output data. This
      allows researchers to estimate and validate both the pathway's structure as well
      as the kinetic constants. In this paper, the recently published 'Proximate
      Parameter Tuning' (PPT) method for the identification of biochemical networks is
      analysed. In particular, it is shown that the described PPT algorithm is
      essentially equivalent to a sequential linear programming implementation of a
      constrained optimization problem. The corresponding objective function consists
      of two parts, the first emphasises the data fitting where a residual 1-norm is
      used, and the second emphasises the proximity of the calculated parameters to the
      specified nominal values, using an infinity-norm. The optimality properties of
      PPT algorithm solution as well as its geometric interpretation are analyzed. The
      concept of optimal parameter locus is applied for the exploration of the entire
      family of optimal solutions. An efficient implementation of the parameter locus
      is also developed. Parallels are drawn with 1-norm parameter deviation
      regularization which attempt to fit the data with a minimal number of parameters.
      Finally, a small example is used to illustrate all of these properties.

PMID- 20049546
TI  - Relationship of opioid use and dosage levels to fractures in older chronic pain
      patients.
AB  - BACKGROUND: Opioids have been linked to increased risk of fractures, but little
      is known about how opioid dose affects fracture risk. OBJECTIVE: To assess
      whether risk of fracture increases with opioid dose among older patients
      initiating sustained use of opioids for chronic non-cancer pain. DESIGN: A cohort
      study that uses Cox proportional hazards models to compare fracture risk among
      current opioid users vs. persons no longer using opioids. PARTICIPANTS: Members
      of an integrated health care plan (N = 2,341) age 60 years and older who received
      3+ opioid prescriptions within a 90-day period for chronic, non-cancer pain
      between 2000 and 2005. MEASUREMENTS: Time-varying measures of opioid use and
      average daily dose in morphine equivalents were calculated from automated data.
      Fractures were identified from automated data and then validated through medical
      record review. RESULTS: Compared with persons not currently using opioids, opioid
      use was associated with a trend towards increased fracture risk (1.28 (95% CI
      (0.99, 1.64 )). Higher dose opioid use (>or=50 mg/day) was associated with a
      9.95% annual fracture rate and a twofold increase in fracture risk (2.00 (95% CI
      (1.24, 3.24)). Of the fractures in the study cohort, 34% were of the hip or
      pelvis, and 37% were associated with inpatient care. CONCLUSIONS: Higher doses
      (>or=50 mg/day) of opioids for chronic non-cancer pain were associated with a
      2.00 increase in risk of fracture confirmed by medical record review. Clinicians
      should consider fracture risk when prescribing higher-dose opioid therapy for
      older adults.

PMID- 20049547
TI  - Patient factors associated with guideline-concordant treatment of anxiety and
      depression in primary care.
AB  - OBJECTIVE: To identify associations of patient characteristics (predisposing,
      enabling and need factors) with guideline-concordant care for anxiety and
      depression in primary care. DESIGN: Analysis of data from the Netherlands Study
      of Depression and Anxiety (NESDA). PARTICIPANTS: Seven hundred and twenty-one
      patients with a current anxiety or depressive disorder, recruited from 67 general
      practitioners (GPs), were included. MEASURES: Diagnoses according to the
      Diagnostic and Statistic Manual of Mental Disorders, fourth edition (DSM-IV) were
      made using a structured and widely validated assessment. Socio-demographic and
      enabling characteristics, severity of symptoms, disability, (under treatment for)
      chronic somatic conditions, perceived need for care, beliefs and evaluations of
      care were measured by questionnaires. Actual care data were derived from
      electronic medical records. Criteria for guideline-concordant care were based on
      general practice guidelines, issued by the Dutch College of General
      Practitioners. RESULTS: Two hundred and eighty-one (39%) patients received
      guideline-concordant care. High education level, accessibility of care,
      comorbidity of anxiety and depression, and severity and disability scores were
      positively associated with receiving guideline-concordant care in univariate
      analyses. In multivariate multi-level logistic regression models, significant
      associations with the clinical need factors disappeared. Positive evaluations of
      accessibility of care increased the chance (OR = 1.31; 95%-CI = 1.05-1.65; p =
      0.02) of receiving guideline-concordant care, as well as perceiving any need for
      medication (OR = 2.99; 95%-CI = 1.84-4.85; p < 0.001), counseling (OR = 2.25; 95%
      CI = 1.29-3.95; p = 0.005) or a referral (OR = 1.83; 95%-CI = 1.09-3.09; p =
      0.02). A low educational level decreased the odds (OR = 0.33; 95%-CI = 0.11-0.98;
      p = 0.04) of receiving guideline-concordant care. CONCLUSIONS: This study shows
      that education level, accessibility of care and patients' perceived needs for
      care are more strongly associated with the delivery of guideline-concordant care
      for anxiety or depression than clinical need factors. Initiatives to improve GPs'
      communication skills around mental health issues, and to improve recognition of
      people suffering from anxiety disorders, could increase the number of patients
      receiving treatment for depression and anxiety in primary care.

PMID- 20049549
TI  - Medical care of hepatitis B among Asian American populations: perspectives from
      three provider groups.
AB  - BACKGROUND: Physicians can play a significant role in helping to decrease the
      hepatitis B virus (HBV) burden among Asian Americans. Few studies have described
      knowledge and practice patterns in the medical community among different provider
      types regarding HBV and liver cancer. OBJECTIVE: Our study explores the HBV
      beliefs, attitudes and practice patterns of medical providers serving Asian
      American communities. DESIGN: We conducted three focus groups with primary care
      providers, liver specialists, and other providers predominantly serving Asian
      American community. We asked about practices and barriers to appropriate medical
      care and outreach. PARTICIPANTS: We moderated three focus groups with 23
      participants, 18 of whom completed and returned demographic surveys. Twelve were
      of Asian ethnicity and 13 spoke English as a second language. Only eight screened
      at least half of their patients, most (72%) using the hepatitis B surface antigen
      test. APPROACH: We used grounded theory methods to analyze focus group
      transcripts. RESULTS: Participants frequently discussed cultural and financial
      barriers to hepatitis care. They admitted reluctance to screen for HBV because
      patients might be unwilling or unable to afford treatment. Cultural differences
      were discussed most by primary care providers; best methods of outreach were
      discussed most by liver specialists; and alternative medicine was discussed most
      by acupuncturists and other providers. CONCLUSIONS: More resources are needed to
      lower financial barriers complicating HBV care and encourage providing guideline
      recommended screenings. Other providers can help promote HBV screening and
      increase community and cultural awareness.

PMID- 20049550
TI  - Biliary complications secondary to post-cholecystectomy clip migration: a review
      of 69 cases.
AB  - INTRODUCTION: Post-cholecystectomy clip migration (PCCM) is rare and can lead to
      complications which include clip-related biliary stones. Most have been reported
      as case reports. This study reviews cases of clip migration reported in the
      literatures. METHOD: Searches and reviews of the literatures from "PubMed,"
      "EMBASE," and "Google Scholar" search engines using the keywords "clip migration"
      and "bile duct stones" were carried out. Eighty cases from 69 publications were
      identified but details for only 69 cases were available for the study. RESULTS:
      The median age at presentations of PCCM was 60 years old (range, 31 to 88 years;
      female, 61.8%) and the median time from the initial cholecystectomy to clinical
      presentations was 26 months (range, 11 days to 20 years). Of primary surgeries,
      23.2% was for complicated gallstones disease. The median number of clips placed
      during surgery was six (range, two to more than ten clips). Common diagnoses at
      presentations of PCCM were obstructive jaundice (37.7%), cholangitis (27.5%),
      biliary colic (18.8%), and acute pancreatitis (8.7%). The median number of
      migrated clip was one (range, one to six). Biliary dilatation and strictures were
      encountered in 74.1% and 28.6%, respectively. Of the 69 cases of PCCM-associated
      complications, 53 (77%) were successfully treated with endoscopic retrograde
      cholangiopancreatography (ERCP), 14 (20.2%) with surgery, and one (1.4%) with
      successful percutaneous transhepatic cholangiography treatment. One patient had
      spontaneous clearance of PCCM. There was no reported mortality related to PCCM.
      CONCLUSION: PCCM can occur at any time but typically occur at a median of 2 years
      after cholecystectomy. Clinical presentations are similar to those with primary
      or secondary choledocholithiasis. Most can be managed successfully with ERCP.

PMID- 20049551
TI  - Epidemiology and prognostic factors in acute superior mesenteric artery
      occlusion.
AB  - BACKGROUND: Reports on trends in incidence and mortality of acute superior
      mesenteric artery (SMA) occlusion and evaluation of prognostic factors in recent
      years are lacking. METHODS: Patients with acute SMA occlusion were identified
      through the in-patient and autopsy registry between 1970 and 1982 (n = 270), 1987
      to 1996 (n = 135), and 2000 and 2006 (n = 100) in Malmo, Sweden. RESULTS: The
      overall incidence rate decreased from 8.6 to 5.4/100,000 person years and the
      autopsy rate from 87% to 25% over time. A higher serum creatinine level was
      associated with a lower probability of undergoing multi-detector row computed
      tomography with intravenous contrast (MDCTiv) (p = 0.006). Not performing a
      MDCTiv (odds ratio 4.0; 95% confidence interval [1.0-16.0]) remained as
      independent prognostic factor for in-hospital mortality. General and vascular
      surgeons collaborated in 25 out of 61 patients that underwent an intervention, of
      which 21 (84%) (p < 0.001) survived. CONCLUSIONS: A close collaboration between
      radiologists and general and vascular surgeons seems to be most important to
      lower the mortality in patients with acute SMA occlusion.

PMID- 20049554
TI  - Properties evaluation of a new MRI contrast agent based on Gd-loaded
      nanoparticles.
AB  - Nanosized materials of gadolinium oxide can provide high-contrast enhancement in
      magnetic resonance imaging (MRI). The aim of this research was to characterize a
      novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and
      gadolinium (III) oxide (Gd2O3) nanoparticles. The size and morphological
      structure of this nanoparticle are determined by particle size analysis device
      (zeta sizer) and transmission electronic microscope. We determined composition of
      Gd2O3 nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic
      resonance signal by T1-weighted MRI. Cytotoxicity of Gd2O3 nanoparticles in SK
      MEL-3 cancer cells was evaluated. Zeta sizer showed Gd2O3 nanoparticles to be 75
      nm in size. EDXA indicated the two main chemical components of gadolinium
      nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a
      significantly higher incremental relaxivity for Gd2O3 nanoparticles compared to
      Magnevist (conventional contrast agent). In such concentrations, the slope of R1
      relaxivity (1/T1) vs. concentration curve of Magnevist and Gd2O3 were 4.33, 7.98
      s-1 mM-1. The slope of R2 relaxivity (1/T2) vs. concentration curve of Magnevist
      and Gd2O3 were 5.06, 13.75 s-1 mM-1. No appreciable toxicity was observed with
      Gd2O3 nanoparticles. Gadolinium-nanocomposite polymer emulsion is well
      characterized and has potential as a useful contrast agent for magnetic resonance
      molecular imaging.

PMID- 20049553
TI  - Fluorine-induced apoptosis and lipid peroxidation in human hair follicles in
      vitro.
AB  - Fluoride is an essential trace element for human body; however, exposure to high
      amounts of fluoride has been documented to be correlated with an increasing risk
      of hair loss. To date, little is known about the mechanism(s) of how fluoride
      affects hair follicles. Here, we demonstrated that middle (1.0 mmol/L) and high
      (10.0 mmol/L) concentrations of sodium fluoride (NaF) significantly inhibited
      hair follicle elongation in vitro, but low NaF (0.1 mmol/L) showed little
      influence. Moreover, treatment with high levels of NaF resulted in a marked
      increase in terminal dUTP nick end labeling-positive cells in the outer layer of
      the outer root sheath, the dermal sheath, and the lower bulb matrix surrounding
      dermal papilla. Furthermore, the enhanced apoptosis was coupled with an increased
      oxidative stress manifested as higher malondialdehyde content. Additionally, the
      presence of selenium considerably antagonized the effects of middle NaF on hair
      follicles, with regard to either the suppression of hair growth or the induction
      of oxidative stress and apoptosis. In conclusion, exposure to high levels of
      fluoride compromises hair follicle growth and accelerate cell apoptosis in vitro.
      The toxicity of fluoride can be reduced by selenium, at least partially via the
      suppression of intracellular oxidative stress.

PMID- 20049555
TI  - Magnetic screening of the potential targeted protein of salvianolic acid B using
      T7 phage display library.
AB  - Salvianolic acid B is one of the effective components from the Chinese
      traditional drug Salvia miltiorrhiza (Danshen), which is widely used as a usual
      clinic drug for atherosclerosis-related disorder patients in China. But the
      targeting protein of salvianolic acid B is still not known. The possible
      targeting proteins of salvianolic acid B were explored by high throughput
      screening in this paper. Attached to the magnetic nanoparticles, salvianolic acid
      B was used for screening the high-affinity protein from the displaying cDNA
      peptide library phage. After biopanning, the selected protein or peptide
      sequences were used to explore the whole proteins containing the selected
      sequences in the National Center for Biotechnology Information website using
      blast. One of the selected phages was carried out by affinity analysis with
      salvianolic acid B using capillary electrophoresis (CE). The CE results indicated
      that the protein or peptide on the surface of the selected phages could bind the
      drug salvianolic acid B. The results are helpful to preliminarily explain the
      pharmacology of salvianolic acid B.

PMID- 20049556
TI  - Typing of genetic markers involved in stress response by fluorescent cDNA
      amplified fragment length polymorphism technique.
AB  - Identification of genetic markers involved in stress response to physical factors
      or chemical substances in organisms is a challenging task. Typing of upregulated
      gene expression due to selective antibacterial pressure is a promising approach
      in the search of molecular mechanisms responsible for development of resistance.
      cDNA-Fluorescent Amplified Fragment Length Polymorphism (cDNA-FAFLP) strategy was
      developed and applied in the search of antimycotic drug resistance marker(s) in
      medically important fungi as an alternative method to microarray analysis. We
      compared differential gene expression of two sensitive Candida albicans reference
      strains (ATCC 10231 and ATCC 60133) and two of their paired resistant to
      fluconazole and itraconazole mutants. Resistant mutants Candida albicans FLC-R,
      resistant to fluconazole (MIC > 128 microg/ml) and Candida albicans ICZ-R,
      resistant to itraconazole (MIC > 4 microg/ml) were obtained in subcultures with
      gradual increase of the antifungal in the culture medium. cDNA-AFLP profile in
      both itraconazole resistant mutants showed specific spectrophotometric peaks with
      5-6-fold RNA overexpression product of 500 bp length compared to the sensitive
      strains. Fluconazole mutants do not reveal RNA level changes under tested by us
      typing conditions. These results indicate that the cDNA-FAFLP strategy is a
      relatively rapid, simple, and reliable method for simultaneous typing of both
      constitutive and induced differences in expression of host genes providing
      insight into the biological processes involved in response to drugs in bacteria
      and fungi. Moreover, this methodology could be tested for typing of the genome
      response of any organism to physical or chemical stress factors.

PMID- 20049557
TI  - Dosage-dependent gene expression from direct repeat locus in rice developed by
      site-specific gene integration.
AB  - In the standard plant transformation practice, transgene copy number is often
      inversely correlated with transgene expression. As the integration locus
      generated by standard methods is mostly complex, consisting of both full-length
      and partial copies arranged in direct or inverted repeat configurations, it is
      difficult to parse the effect of copy number and locus structure. To clearly
      study the effect of transgene copy number on gene expression, it is important to
      control the locus structure and integrate full-length copies. In this study, the
      effect of transgene copy number on transgene expression in plant cells was
      determined using rice callus as a model. To generate full-length integrations,
      Cre-lox-mediated site-specific gene integration method was used. Transgenic rice
      lines consisting of one to three copies of beta-glucuronidase or green
      fluorescent protein genes were developed. Site-specific integration lines were
      characterized and subjected to expression analysis. Lines containing two or three
      copies of either reporter genes displayed 2-4 times higher expression compared to
      the single-copy lines. Therefore, dosage-dependent transgene expression can be
      obtained by integrating full-length copies, and site-specific gene integration
      approach can serve as an efficient tool for generating precise multi-copy
      integrations.

PMID- 20049558
TI  - Primary lymphoma of bone: a case report and review of the literature.
AB  - The purpose of this study was to investigate the clinical signs and therapy of
      primary lymphoma of bone (PLB). One primary lymphoma of bone is described, and
      review of the pertinent literature is introduced. The patient achieved complete
      remission with no evidence of local recurrence. PLB are uncommon malignancies.
      Patients with PLB commonly present with local bone pain, soft tissue swelling and
      a mass or a pathological fracture. Most cases of PLB are classified as diffuse
      large B-cell lymphomas in the WHO classification of hematological malignancies.
      Comprehensive immunohistochemical studies are required to establish an accurate
      histological diagnosis of PLB. Early diagnosis and active treatment can improve
      the prognosis.

PMID- 20049559
TI  - Renal disorder preceding multiple myeloma.
AB  - Renal disorders preceding multiple myeloma (MM) is a rare type of presentation
      for plasma cell dyscrasias. We report a case of 40-year-old female who first
      admitted to the hospital with symptoms and signs of weight loss, nausea and
      vomiting, and with findings of proteinuria renal dysfunction and anemia. Renal
      biopsy revealed light chain deposition and findings mimicking
      membranoproliferative glomerulonephritis (MPGN). Investigation of the patient for
      plasma cell dyscrasia was resulted in normal findings. After 28 months, she was
      re-evaluated and MM was diagnosed.

PMID- 20049560
TI  - High response of second-line chemotherapy with pemetrexed or gemcitabine combined
      with carboplatin in patients with non-small-cell lung cancer experiencing
      progression following 6 months after concluding platinum-based chemotherapy.
AB  - Because of improved therapeutic results after first-line platinum-based
      chemotherapy in patients with stage IV non-small-cell lung cancer (NSCLC), second
      line chemotherapy may be considered for a growing number of patients.
      Approximately, 10% of patients have an interval time after concluding first-line
      platinum-based chemotherapy greater than 6 months. These patients may achieve
      high tumor responses when platinum is again used in second-line treatment. Twenty
      three patients experiencing progression following 6 months after concluding
      platinum-based chemotherapy were managed with second-line treatment with
      carboplatin combined with gemcitabine or pemetrexed. Overall response,
      progression-free survival (PFS), and overall survival (OS) after initiation of
      second-line treatment were calculated for all patients. Median PFS after first
      line treatment was 12.6 months (95% confidence interval [95% CI], 10.4-14.7
      months). Partial response was achieved in 7 of 23 patients, resulting in an
      overall response of 30.4% (95% CI, 11.6-49.0). Following initiation of second
      line chemotherapy, median PFS was 5.9 months (95% CI, 1-10.9 months) and median
      OS was 12.5 months (95% CI, 3.5-21.5 months). The 1-year survival rate for all
      patients was 61.0% (95% CI, 29.5-82.0). Adding these results to those of the 10
      previously published trials, 75 of 326 patients, 23%, (95% CI, 18.7-27.3)
      presented an overall response with the use of second-line platinum-based
      chemotherapy. The use of platinum combinations as second-line chemotherapy seems
      to have a place in the management of patients with advanced NSCLC, especially
      those with an interval time to progression greater than 6 months.

PMID- 20049561
TI  - Randomized, double-blind, crossover study of palonosetron compared with
      granisetron for the prevention of chemotherapy-induced nausea and vomiting in a
      Chinese population.
AB  - The objective of this study was to compare the efficacy and tolerability of
      palonosetron and granisetron in a Chinese population receiving highly emetogenic
      cisplatin-based chemotherapy or moderately emetogenic chemotherapy. Patients were
      stratified by chemotherapy with cisplatin (yes/no) and then randomly assigned to
      receive either palonosetron (0.25 mg i.v.) in the first cycle followed by
      granisetron (3 mg i.v.) in the second cycle or vice versa. The primary efficacy
      endpoint was the proportion of patients with complete response 0-24 h post
      chemotherapy administration. The proportions of patients with complete response
      24-120 and 0-120 h following chemotherapy were also compared. Of the 144 patients
      randomized, 36 (25%) received 60-80 mg/m(2) cisplatin; 66 of 72 patients in the
      palonosetron to granisetron group and 56 of 72 patients in the granisetron to
      palonosetron group completed treatment with both antiemetics. The efficacy and
      safety analyses included 128 palonosetron treatments and 138 granisetron
      treatments. Palonosetron consistently produced numerically higher complete
      response rates than granisetron in the acute phase (0-24 h, 71.09 vs. 65.22%),
      the delayed phase (24-120 h, 60.16 vs. 55.80%), and overall (0-120 h, 53.13 vs.
      50.00%) though the differences were not significant. Both palonosetron and
      granisetron were well tolerated. Palonosetron was well tolerated and effective in
      preventing acute and delayed chemotherapy-induced nausea and vomiting in a
      Chinese population. When used as monotherapy, 0.25-mg palonosetron was not
      inferior to 3-mg granisetron for preventing vomiting following highly or
      moderately emetogenic chemotherapy.

PMID- 20049562
TI  - Survival in 12,653 breast cancer patients with extensive axillary lymph node
      metastasis in the anthracycline era.
AB  - Institutional data are conflicting regarding the prognosis of breast cancer
      patients with extensive (>=10) axillary lymph node (ALN) metastases. We
      hypothesized that overall survival (OS) and disease specific survival (DSS)
      improved after the introduction of anthracycline-based therapy in 1997. We used
      the Surveillance, Epidemiology, and End results (SEER) database to identify
      breast cancer patients with >=10 ALN metastases diagnosed between 1988 and 2004.
      Patients were categorized according to whether they were diagnosed prior to the
      FDA approval of anthracyclines (pre-anthracycline era, pre-AE) or after approval
      (post-anthracycline era, post-AE). Univariate analyses of OS and DSS were
      performed using the Kaplan-Meier method and differences assessed via the log rank
      test. Anthracycline era as an independent predictor of OS and DSS was evaluated
      using Cox proportional hazards models with patient age, hormone receptor status,
      tumor size, use of radiation therapy, and number of metastatic ALNs as
      covariates. Entry criteria were met by 12,653 patients. Of these, 5,655 (44.7%)
      and 6,998 (55.3%) were treated in the pre-AE and post-AE, respectively. On
      univariate analysis, post-AE patients experienced significantly improved rates of
      OS (P<0.001) and DSS (P<0.001) relative to pre-AE patients. On multivariate
      analysis, treatment in the post-AE favorably influenced both OS (Hazard Ratio
      [HR] 0.90, 95% Confidence Interval [CI] 0.84-0.96) and DSS (HR 0.84, CI 0.79
      0.91). Both OS and DSS are poor in patients with extensive ALN metastases.
      Patients with advanced breast cancer treated in the post-AE demonstrated superior
      OS and DSS.

PMID- 20049563
TI  - Identification of tyrosine phosphoproteins in signaling pathway triggered TGF-a
      by using functional proteomics technology.
AB  - Although several groups had conducted proteomics of nasopharyngeal carcinoma
      (NPC), little study was involved in phosphoproteomics, oncogenic signaling, and
      cancer research about NPC. Analysis of phosphotyrosine proteins from transforming
      growth factor alpha (TGF-a) triggered phosphotyrosine proteome permitted the
      identification of novel downstream substrates of the epidermal growth factor
      receptor (EGFR). Using functional proteomics technology based on 2-DE, 2-D
      western blotting, and mass spectrometry, we identified and quantified the
      tyrosine phosphorylation levels of 16 proteins between control and TGF-a-treated
      CNE2 human NPC cells. Among these proteins, tyrosine phosphorylated levels of ten
      proteins were increased, and those of six proteins were decreased in TGF-a
      treated CNE2 cells compared with control. In addition, among these identified
      proteins, ANXA3, KRT8, and KRT18 were validated to be novel tyrosine
      phosphorylation targets of EGFR signaling by IP-western blotting and part of a
      complex EGFR phosphotyrosine signaling network. These novel findings will provide
      new insights into the complex EGFR phosphorylation signaling and may have
      implications in molecular cancer therapy of NPC.

PMID- 20049564
TI  - Characterization of chronic idiopathic thrombocytopenic purpura in Japanese
      children: a retrospective multi-center study.
AB  - The objectives of this study are to clarify (1) the difference in demographic and
      clinical variables at initial presentation between acute and chronic idiopathic
      thrombocytopenic purpura (ITP), and (2) the prognostic factors of patients with
      chronic ITP. We conducted a retrospective analysis of 247 children with newly
      diagnosed ITP between April 1991 and March 2006 who visited one of the 12
      hospitals belonging to the Kyoto University Pediatric Hematologic Study Group.
      180 and 67 cases were classified as the acute type and as the chronic type,
      respectively. Older age, higher initial platelet count, positive medical history
      or concomitant medical diagnosis, the absence of preceding infection or
      vaccination, and the absence of an increase in immunoglobulin were risk factors
      for the chronicity. The prognostic factors in chronic ITP were evaluated in 53
      patients after excluding patients receiving splenectomy or having insufficient
      follow-up data. The overall time required for 50% resolution in patients with
      chronic ITP was approximately 5.6 years. Age at presentation of less than 3 years
      and higher platelet counts at the time of chronic ITP diagnosis were good
      prognostic factors. On the other hand, gender, initial platelet counts, and
      preceding infection or vaccination were not associated with the prognosis.

PMID- 20049565
TI  - CD56 expression in human myeloma cells derived from the neurogenic gene
      expression: possible role of the SRY-HMG box gene, SOX4.
AB  - CD56 is frequently detected on primary myeloma cells from more than 80% patients
      with overt myeloma. In order to clarify the possible mechanisms of CD56
      expression in human myeloma, we underwent screening for potential targets by
      microarray analysis, where the CD56(+) myeloma cell lines showed markedly
      increased expressions of transcription factors involved in the neuronal cell
      lineage compared to the CD56(-) myeloma cell lines. Here, we show that among the
      SOX family of transcription factors, SOX4 was highly up-regulated and SOX1 was
      down-regulated in the CD56(+) myeloma cell lines as well as in primary myeloma
      cases as confirmed by the RT-PCR. ChIP analysis of the CD56 promoter region
      showed specific bindings of SOX4 in the CD56(+) and SOX1 in the CD56(-) myeloma
      cell lines, respectively. shRNA against SOX1 failed to induce CD56 expression in
      CD56(-) myeloma cell line, U266. On the contrary, over-expression of SOX4 in the
      CD56(-) myeloma cell line could induce the CD56 expression. Silencing of SOX4 by
      shRNA transfection down-regulated CD56 expression and induced apoptosis to
      CD56(+) human myeloma cell line, AMO1. Thus, induction of SOX4 gene expression
      might be responsible for the CD56 expression in human myeloma cells.

PMID- 20049566
TI  - Should gram stains have a role in diagnosing hip arthroplasty infections?
AB  - BACKGROUND: The utility of Gram stains in diagnosing periprosthetic infections
      following total hip arthroplasty has recently been questioned. Several studies
      report low sensitivity of the test, and its poor ability to either confirm or
      rule out infection in patients undergoing revision total hip arthroplasty.
      Despite this, many institutions including that of the senior author continue to
      perform Gram stains during revision total hip arthroplasty. QUESTIONS/PURPOSES:
      We assessed the sensitivity, specificity, accuracy, and positive and negative
      predictive values of Gram stains from surgical-site samplings taken from
      procedures on patients with both infected and aseptic revision total hip
      arthroplasties. METHODS: A review was performed on patients who underwent
      revision total hip arthroplasty between 2000 and 2007. Eighty-two Gram stains
      were performed on patients who had infected total hip arthroplasties and
      underwent revision procedures. Additionally, of the 410 revision total hip
      arthroplasties performed on patients who were confirmed infection-free, 120 Gram
      stains were performed. Patients were diagnosed as infected using multiple
      criteria at the time of surgery. Sensitivity, specificity, positive and negative
      predictive values, and accuracy were calculated from these Gram stain results.
      RESULTS: The Gram stain demonstrated a sensitivity and specificity of 9.8% and
      100%, respectively. In this series, the Gram stain had a negative predictive
      value of 62%, a positive predictive value of 100%, and an accuracy of 63%.
      CONCLUSIONS: Gram stains obtained from surgical-site samples had poor sensitivity
      and poor negative predictive value. Based on these findings, as well as those of
      other authors, we believe that Gram stains should no longer be considered for
      diagnosing infections in revision total hip arthroplasty. LEVEL OF EVIDENCE:
      Level III, diagnostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20049567
TI  - Partial-thickness articular surface rotator cuff tears: an all-inside repair
      technique.
AB  - BACKGROUND: Treatment of partial-thickness articular surface rotator cuff tears
      varies from simple debridement with or without an acromioplasty to various repair
      techniques. These repair techniques have included in situ transtendinous methods,
      as well as completion of the tear and repairing the full-thickness defect. The
      transtendinous techniques can be associated with stiffness and completing the
      tear takes down normal intact tissue. Therefore, a technique was developed that
      repairs the articular-side partial- thickness rotator cuff tears with an all
      inside approach that does not violate the intact bursal tissue and does not
      complete the tear. QUESTIONS/PURPOSES: To compare the preoperative and
      postoperative Penn shoulder scores (PSS) associated with an in situ all-inside
      repair technique and the effects of such a repair on postoperative stiffness.
      METHODS: Twenty patients with partial-thickness articular rotator cuff tears
      greater than 50% of the width of the tendon repaired with an all-inside repair
      technique were retrospectively reviewed. Two of the patients were high school
      athletes and the rest self-described as recreational athletes. The minimum
      followup was 16 months (average, 29 months; range, 16-41 months). A validated
      outcome measure (PSS) was used to assess clinical outcome, and postoperative ROM
      was measured. RESULTS: The average PSS score improved from 74 (range, 56-84) to
      92 (range, 86-99). All but one patient was able to return to the same level of
      play or higher. CONCLUSIONS: In situ repairs of partial-thickness articular
      surface tears using an all-inside approach resulted in a substantial increase in
      PSS with no cases of major postoperative clinical stiffness. LEVEL OF EVIDENCE:
      Level IV, therapeutic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20049568
TI  - Carpal and cubital tunnel syndrome: who gets surgery?
AB  - BACKGROUND: Despite the prevalence of carpal and cubital tunnel syndrome, and
      relief of symptoms following timely surgical release, it is unclear how
      nonclinical patient characteristics affect disease management.
      QUESTIONS/PURPOSES: We examined the effects of a variety of factors, such as age,
      gender, and socioeconomic status on the management of both carpal and cubital
      tunnel syndromes. PATIENTS AND METHODS: We retrospectively reviewed the records
      of all 273 patients seen by two hand surgeons with a diagnosis of either carpal
      or cubital tunnel syndrome between January 2005 and January 2007. Demographic,
      clinical (diagnosis, treatment), and socioeconomic (insurance type, median
      income) information was collected. Census data (2000) were used to collect
      information on median household income. The average age was 52 years (range, 19
      87 years), and 65% of the patients were women (n = 178). Eighteen patients had
      Workers Compensation. Of the 273 patients, 86 (32%) had two or more diagnoses.
      RESULTS: Among patients with carpal tunnel syndrome, there was a higher
      proportion of female patients compared to male patients (68% versus 32%); male
      patients with multiple neuropathies had higher rates of surgery than their female
      counterparts (63% versus 41%). Only increasing age was associated with increasing
      likelihood of surgery. Among multiple-diagnosis patients, those with Workers
      Compensation (n = 6) had higher wait times for surgery than their counterparts (n
      = 46) (126 days versus 26 days). CONCLUSION: Patient age was the most important
      predictor of surgical release, and among those with multiple neuropathies, male
      patients were more likely to have surgery than female patients. Patients with
      Workers Compensation may experience long wait times to surgery. LEVEL OF
      EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 20049569
TI  - Tendon properties remain altered in a chronic rat rotator cuff model.
AB  - BACKGROUND: Chronic rotator cuff tears are often associated with pain or poor
      function. In a rat with only a detached supraspinatus tendon, the tendon heals
      spontaneously which is inconsistent with how tears are believed to heal in
      humans. QUESTIONS/PURPOSES: We therefore asked whether a combined supraspinatus
      and infraspinatus detachment in the rat would fail to heal and result in a
      chronic injury in the supraspinatus tendon. METHODS: We acutely detached the
      supraspinatus and infraspinatus tendons in a rat model. At 4, 8, and 16 weeks
      post-detachment, biomechanical testing, collagen organization, and histological
      grading were evaluated for the detached supraspinatus and infraspinatus tendons
      and compared to controls. RESULTS: In the detached supraspinatus tendon, area and
      percent relaxation were increased at all time points while the modulus and
      stiffness were similar to those of controls at 4 and 8 weeks. Collagen
      disorganization increased at late time points while cellularity increased and
      cells were more rounded in shape. In the detached infraspinatus tendon, area and
      percent relaxation were also increased at late time points. However, the modulus
      values initially decreased followed by an increase in both modulus and stiffness
      at 16 weeks compared to control. In the detached infraspinatus, we also observed
      a decrease in collagen organization at all time points and increased cellularity
      and a more rounded cell shape. CONCLUSIONS: Due to the ongoing changes in
      mechanics, collagen organization and histology in the detached supraspinatus
      tendon compared to control animals at 16 weeks, this model may be useful for
      understanding the human chronic tendon tear. CLINICAL RELEVANCE: This rat rotator
      cuff chronic model can be used to test hypotheses regarding injury and repair
      mechanisms that cannot be addressed in human patients or in cadaveric studies.

PMID- 20049571
TI  - High hip center technique using a biconical threaded Zweymuller cup in
      osteoarthritis secondary to congenital hip disease.
AB  - BACKGROUND: The high hip center technique used for a deficient acetabulum is
      reconstruction of the hip at a high center of rotation. In the literature, there
      is no consensus regarding the value of this technique. QUESTIONS/PURPOSES: We
      investigated whether the new-generation biconical threaded Zweymuller cup fixed
      in a high nonanatomic position in patients with arthritis secondary to congenital
      hip disease experienced different rates of polyethylene wear and long-term
      survivorship when compared with anatomically positioned cups. PATIENTS AND
      METHODS: We studied the polyethylene wear rate and Kaplan-Meier survivorship of
      104 titanium threaded Zweymuller cups in 88 patients (81 females), placed in 70
      hips at near-normal hip center and in 34 hips at a high hip center position at a
      distance of 31.1 to 60 mm (mean, 39.7 mm) from the interteardrop line. Minimum
      followup was 2 years (mean +/- SD, 8.6 +/- 3.5 years; range, 2-15 years).
      RESULTS: The mean linear polyethylene wear rates in the near-normal and high hip
      center groups were not different (0.110 +/- 0.050 mm and 0.113 +/- 0.057 mm,
      respectively). The Kaplan-Meier 15-year cup survivorship rates with revision for
      any reason as an event of interest in the near-normal and high hip center groups
      also were not different (97.2% [95% confidence interval, 88.5%-99.3%] and 97.1%
      [95% confidence interval, 73.8%-99.3%], respectively). CONCLUSIONS: The high hip
      center technique using a biconical threaded Zweymuller cup in patients with
      arthritis secondary to congenital hip disease results in a polyethylene wear rate
      and long-term cup survivorship comparable to those observed in anatomically
      positioned cups. LEVEL OF EVIDENCE: Level III, therapeutic study. See the
      Guidelines for Authors for a complete description of level of evidence.

PMID- 20049572
TI  - Postoperative analgesia in TKA: ropivacaine continuous intraarticular infusion.
AB  - BACKGROUND: Postoperative pain control is a challenge in patients undergoing TKA
      due to side effects and technical limitations of current analgesic approaches.
      Local anesthetic infiltration through continuous infusion pumps has been shown to
      reduce postoperative pain in previous studies. QUESTIONS/PURPOSES: We assessed
      the effectiveness of intraarticular ropivacaine infusions in reducing pain and
      postoperative opioid use after TKA and determined whether such infusions
      accelerate functional recovery of the patient and reduce length of hospital stay.
      METHODS: In a randomized, prospective, double-blind study, two groups were
      assigned: Group A (n = 25) underwent continuous intraarticular infusion with 300
      mL ropivacaine 0.2% at a speed of 5 mL/hour through an elastomeric infusion pump
      and Group B (n = 25) had an elastomeric pump insertion with 300 mL saline
      solution at an infusion speed of 5 mL/hour. All patients had the same prosthesis
      model implanted. Parameters analyzed over the first 3 days, at discharge, and 1
      month later included postoperative pain, joint function, opioid use, and length
      of hospital stay. RESULTS: All patients in Group A showed a decrease in pain
      intensity measured by a visual analog scale and opioid use in the first 3 days.
      Mean length of hospital stay was also reduced in Group A (5.72 days) compared to
      Group B (7.32 days). There were no device-related complications. CONCLUSIONS: Use
      of an infusion pump is effective in treating pain after TKA, reducing
      postoperative pain and opioid use. It also improves immediate functionality and
      patient comfort, reducing the mean length of hospital stay, without increasing
      the risk of complications. LEVEL OF EVIDENCE: Level I, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 20049573
TI  - Indications for reverse total shoulder arthroplasty in rotator cuff disease.
AB  - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) was introduced to treat
      rotator cuff tear arthropathy but is now used to treat a variety of problems.
      Although its use has expanded substantially since the FDA's approval in 2004, the
      appropriateness in patients with rotator cuff disease is unclear.
      QUESTIONS/PURPOSES: We review the use of RTSA in patients with rotator cuff
      disease to (1) describe classification of rotator cuff tear reparability and the
      concept of a balanced shoulder; (2) explore the theory behind RTSA design
      relative to rotator cuff arthropathy; (3) discuss the indications and
      contraindications for RTSA; and (4) review published outcomes of RTSA for rotator
      cuff arthropathy. METHODS: We performed a selective review of the literature on
      the use of RTSA in the treatment of rotator cuff disease. RESULTS: Modern RTSA
      designs restore deltoid tension and a functional fulcrum to the rotator cuff
      deficient shoulder, which allows recovery of active shoulder elevation and
      effectively restores function in short- and medium-term followup studies.
      CONCLUSIONS: In short-term followup the RTSA relieves symptoms and restores
      function for patients with cuff tear arthropathy and irreparable rotator cuff
      tears with pseudoparalysis (preserved deltoid contraction but loss of active
      elevation). Severely impaired deltoid function, an isolated supraspinatus tear,
      and the presence of full active shoulder elevation with a massive rotator cuff
      tear and arthritis are contraindications to RTSA. CLINICAL RELEVANCE: For
      properly selected patients who have symptomatic and disabling rotator cuff
      deficiency, RTSA can result in life-changing improvements in pain, motion,
      function, and patient satisfaction. LEVEL OF EVIDENCE: Level V therapeutic study.
      See Guidelines for Authors for a complete description of levels of evidence.

PMID- 20049575
TI  - Accidental fracture of the tip of the Coopdech bronchial blocker during insertion
      for one lung ventilation.
AB  - PURPOSE: The distal tip of a Coopdech bronchial blocker has a preformed
      angulation to aid placement in the desired bronchus. We report two cases wherein
      this design may have resulted in distal tip fracture due to entanglement at the
      level of the Murphy's eye of the endotracheal tube or at the carina. CLINICAL
      FEATURES: A 49-yr-old female had a Coopdech bronchial blocker inserted into her
      right main bronchus for video-assisted thoracoscopic (VAT) lung biopsy.
      Resistance was encountered on its insertion, followed by confirmation of its
      position by fibreoptic bronchoscopy. As lung isolation was inadequate,
      bronchoscopy was repeated during surgery. This showed fracture of the blocker tip
      that required patient repositioning and insertion of another blocker. In a second
      incident, a bronchial blocker was inserted into the right main bronchus of a 19
      yr-old male for VAT bullectomy. This procedure was performed under continuous
      fibreoptic guidance. Nevertheless, it was difficult to pass the blocker tip
      beyond the Murphy's eye of the endotracheal tube, as repeated attempts resulted
      in its entanglement and fracture. Another blocker was inserted by maneuvering the
      tip beyond the Murphy's eye. CONCLUSION: The preformed tip of the Coopdech
      bronchial blocker can be damaged at the Murphy's eye of the endotracheal tube or
      at the carina. This can result in tip fracture, especially during insertion into
      the right main bronchus. Maneuvering the tip away from the Murphy's eye can
      circumvent this problem. Continuous bronchoscopic guidance should be used as
      recommended by the manufacturer.

PMID- 20049574
TI  - Calcium influx measured at single presynaptic boutons of cerebellar granule cell
      ascending axons and parallel fibers.
AB  - Action potential-evoked calcium influx into presynaptic boutons is a key
      determinant of synaptic strength and function. Here, we have examined the calcium
      dynamics at individual presynaptic boutons of the cerebellar granule cells in the
      molecular layer of cerebellar slices and investigated whether different
      subpopulations of granule cell boutons exhibit different calcium dynamics. We
      found that a population of boutons with low basal calcium clearance rates may
      activate a second clearance mechanism and exhibit biphasic calcium decay on high
      calcium influx induced by bursts of action potentials. We also found that boutons
      on ascending axons and parallel fibers show similar calcium influx amplitudes and
      calcium clearance rates in response to action potentials. Lastly, we found that
      parallel fiber boutons located in the inner molecular layer have a higher calcium
      clearance rate than boutons located in the outer molecular layer. These results
      suggest that cerebellar granule cell boutons should not be regarded as a
      homogeneous population, but rather that different subpopulations of boutons may
      exhibit different properties. The heterogeneity of presynaptic boutons may allow
      different learned behaviors to be encoded in the same circuit without mutual
      interference and may be a general mechanism for increasing the computational
      capacity of the brain.

PMID- 20049576
TI  - Rapid sequence induction for appendectomies: a retrospective case-review
      analysis.
AB  - PURPOSE: Rapid sequence induction (RSI) with cricoid pressure is suggested to
      decrease the risk of aspiration of gastric contents. However, the effectiveness
      of RSI has been questioned, and the technique may lead to airway and hemodynamic
      complications. The purpose of this study was to determine the frequency of RSI
      use in patients with acute appendicitis, the types of drugs administered, and the
      occurrence of any complications. METHODS: After approval by the Ethics Committee,
      the charts of patients undergoing appendectomy in a one-year period were examined
      retrospectively. Information was retrieved on Mallampati airway evaluation,
      airway device used, preoxygenation, RSI, and drugs at induction. Reported
      complications were noted, including airway difficulties, hypotension (systolic
      blood pressure < 80 mmHg) and hypertension (>160 mmHg) in the 20-min period after
      induction. RESULTS: General anesthesia with tracheal intubation was used in 248
      of 250 cases reviewed. The Mallampati airway evaluation, preoxygenation, and RSI
      were recorded as performed in 95, 94, and 81% of cases, respectively. Opioids,
      propofol, and neuromuscular blocking agents were given in 98, 98, and 99% of
      patients, respectively. Succinylcholine use was common (80%), with 96% of these
      patients receiving rocuronium precurarization. Difficult intubation with
      successful alternate technique was encountered in three patients (1.2%).
      Hypotension and hypertension occurred in 27% and 8% of patients, respectively.
      There were no documented cases of aspiration. Oxygen desaturation was mentioned
      in one case at induction and in three cases at emergence. CONCLUSION: An RSI with
      opioid, induction agent, and succinylcholine is the technique of choice for
      appendectomies at our institution. The frequency of airway complications is too
      low to recommend a change in practice.

PMID- 20049577
TI  - Temperature and surgical wound heat loss during orthopedic surgery: computer
      simulations and measurements.

PMID- 20049578
TI  - Orogastric tubes do not improve transesophageal echocardiographic imaging during
      cardiac surgery: a randomized trial.
AB  - INTRODUCTION: Image quality is often an overlooked consideration that affects the
      quality and findings of a perioperative transesophageal echocardiography (TEE)
      study. We undertook a study to evaluate the potential benefit of orogastric (OG)
      tube insertion following tracheal intubation as a method to improve TEE image
      quality. METHODS: In this prospective randomized double-blind controlled trial,
      32 adult cardiac surgery patients were randomized to receive either an orogastric
      (OG) tube with suctioning or no OG tube following tracheal intubation and before
      TEE probe insertion. Two independent observers graded the quality of related TEE
      images on a scale from 1 to 4, and the total image scores (total scores out of a
      possible 20) were compared between groups across five different views. All
      analyses were by intention to treat. RESULTS: For the total scores, there was no
      difference between the OG and control groups (mean 12.3 [2.1] vs 12.8 [1.8],
      respectively; P = 0.7). There was a numerically small but statistically
      significant difference in total scores between reviewers (score 2.4 [0.7] vs 2.2
      [0.9]; mean difference -0.2; 95% confidence interval -0.4 to -0.02; P < 0.001).
      For the most part, the raters agreed on the scores for each view. Overall, 96% of
      the total scores were identical or differed by only one point. CONCLUSION: While
      this study was underpowered to detect small changes in image quality, the use of
      an OG tube for routine cases did not improve the overall quality of the related
      images acquired during TEE examination.

PMID- 20049579
TI  - Rare complications associated with epidural blood patches.

PMID- 20049580
TI  - "Pine mouth" syndrome: cacogeusia following ingestion of pine nuts (genus:
      pinus). An emerging problem?
AB  - We report a case of cacogeusia, specifically metallogeusia (a perceived metallic
      or bitter taste) following pine nut ingestion. A 36-year-old male presented with
      cacogeusia one day following ingestion of 10-15 roasted pine nuts (genus: Pinus).
      Symptoms became worst on post-exposure day 2 and progressively improved without
      treatment over 5 days. There were no other symptoms and physical examination was
      unrevealing. All symptoms resolved without sequalae. We contemporaneously report
      a rise in pine nut-associated cacogeusia reported online during the first quarter
      of 2009, and a significant rise in online searches related to pine nut-associated
      cacogeusia (or what the online public has termed "pine mouth") during this time.
      Most online contributors note a similar cacogeusia 1-3 days following pine nut
      ingestion lasting for up to 2 weeks. All cases seem self-limited. Patients
      occasionally describe abdominal cramping and nausea after eating the nuts. Raw,
      cooked, and processed nuts (in pesto, for example) are implicated. While there
      appears to be an association between pine nut ingestion and cacogeusia, little is
      known about this condition, nor can any specific mechanism of specific cause be
      identified. It is not known if a specific species of pine nut can be implicated.
      "Pine mouth" appears to be an emerging problem.

PMID- 20049581
TI  - Outcome following mini-invasive surgical repair of closed Achilles tendon
      rupture.

PMID- 20049582
TI  - Dietary source of stearidonic acid promotes higher muscle DHA concentrations than
      linolenic acid in hybrid striped bass.
AB  - Rapid expansion of aquacultural production is placing increasing demand on fish
      oil supplies and intensified the search for alternative lipid sources. Many of
      the potential alternative sources contain low concentrations of long chain n-3
      fatty acids and the conversion of dietary linolenic acid to longer chain highly
      unsaturated fatty acids is a relatively inefficient process in some species. A 6
      week study was conducted to compare tissue fatty acid (FA) concentrations in
      hybrid striped bass fed either 18:3n-3 (alpha-linolenic acid; ALA) or 18:4n-3
      (stearidonic acid; SDA). Hybrid striped bass were fed either a control diet
      containing fish oil, or diets containing ALA or SDA at three different levels
      (0.5, 1 and 2% of the diet). There were no significant differences in whole
      animal responses between fish fed ALA or SDA. Liver and muscle concentrations of
      ALA and SDA were responsive to dosages fed. However, only 22:6n-3 concentrations
      in muscle were significantly affected by dietary source of 18 carbon precursors.
      Muscle 22:6n-3 concentrations were significantly higher in fish fed SDA compared
      to fish fed ALA. Based on these data, it appears that feeding SDA can increase
      long chain n-3 fatty acid concentrations in fish muscle.

PMID- 20049583
TI  - The spectrum of plant and animal sterols in different oil-derived intravenous
      emulsions.
AB  - Intravenous lipid constituents have different effects on various biological
      processes. Some of these effects are protective, while others are potentially
      adverse. Phytosterols, in particular, seem to be implicated with parenteral
      nutrition-associated cholestasis. The aim of this study is to determine the
      amount of plant and animal sterols present in lipid formulations derived from
      different oil sources. To this end, animal (cholesterol) and plant (beta
      sitosterol, campesterol, and stigmasterol) sterols in seven different
      commercially available intravenous lipid emulsions (ILEs) were quantified by
      capillary gas chromatography after performing a lipid extraction procedure. The
      two major constituents of the lipid emulsions were cholesterol (range 14-57% of
      total lipids) and beta-sitosterol (range 24-55%), followed by campesterol (range
      8-18%) and stigmasterol (range 5-16%). The fish oil-derived formulation was an
      exception, as it contained only cholesterol. The mean values of the different
      sterols were statistically different across ILEs (P = 0.0000). A large percentage
      of pairwise comparisons were also statistically significant (P = 0.000), most
      notably for cholesterol and stigmasterol (14 out of 21 for both), followed by
      campesterol (12 out 21) and beta-sitosterol (11 out 21). In conclusion, most ILEs
      combined significant amounts of phytosterols and cholesterol. However, their
      phytosterols:cholesterol ratios were reversed compared to the normal human diet.

PMID- 20049584
TI  - Use of comparative proteomics to identify key proteins related to hepatic lipid
      metabolism in broiler chickens: evidence accounting for differential fat
      deposition between strains.
AB  - In order to investigate differences in fat metabolism during embryonic
      development, a comparative proteomics strategy was employed using Arbor Acres
      (AA) and San Huang (SH) broiler chickens with different growth and fat deposition
      characteristics. These birds were floor-reared and fed identical diets, and
      embryonic livers were collected from AA and SH chicken embryos on days 9, 14 and
      19 of incubation and hatching. Proteins were extracted and fractionated by two
      dimensional electrophoresis (2-DE), Neuhoff's colloidal Coomassie Blue G-250
      staining was carried out, and stained gels were scanned and analyzed using
      PDQuest7.3 software (Bio-Rad). In-gel trypsin digestion of the differential
      protein spots and matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF-MS) were subsequently assessed. Peptide mass
      fingerprinting of the differentially expressed proteins was performed using the
      server from MASCOT or either Prospector or ProFound, and 37 proteins were
      successfully identified. In the present study, embryo and liver weights showed a
      trend toward enhanced growth during embryonic development. Of the 37 identified
      differential proteins, phosphoenolpyruvate carboxykinase (PEPCK), apolipoprotein
      A-I (Apo A-I), fatty acid-binding protein (L-FABP) and 3-hydroxy-3-methylglutaryl
      Coenzyme A synthase (HMG-CoA synthase) were up-regulated in SH chickens to a
      greater extent than they were in AA chickens. These observations suggest that the
      lipid metabolic proteins and enzymes are inherent characteristics that contribute
      to the apparent differences in fat deposition between the two strains.

PMID- 20049585
TI  - Electron paramagnetic resonance investigation of stratum corneum lipid structure.
AB  - Electron paramagnetic resonance (EPR) in conjunction with a slow-tumbling
      simulation was utilized for defining stratum corneum (SC) lipid structure. We
      found that ordering calculated from the simulation is an appropriate index for
      evaluating SC lipids structure. The SC from two sites (mid-volar forearm and
      lower-leg) of human volunteers was stripped consecutively from one to three times
      using a glass plate coated with a cyanoacrylate resin. Aliphatic spin probes, 5
      doxylstearic acid (5-DSA) and 3beta-doxyl-5alpha-cholestane (CHL), were used to
      monitor SC ordering. EPR spectrum of 5-DSA incorporated in the SC demonstrated a
      characteristic peak for the first strip. However, EPR spectra of CHL in the SC
      did not show a clear difference for each strip, except for the peak intensity.
      The results imply that CHL is not incorporated into the lipid phase as easily as
      5-DSA is. A slow-tumbling simulation of the EPR spectrum was performed to analyze
      the detailed lipid structure. The simulation results for 5-DSA show differences
      in values of the SC ordering as a function of depth. Thus, these results along
      with the simulation analysis provide a detailed SC layer structure.

PMID- 20049586
TI  - The kidney in acute renal failure: innocent bystander, victim or still a suspect?

PMID- 20049587
TI  - The impact of experimental hypoperfusion on subsequent kidney function.
AB  - OBJECTIVE: To investigate the short- and medium-term renal hemodynamic and
      functional responses to both short and sustained hypoperfusion. SUBJECTS: Eleven
      Merinos ewes. SETTING: Animal laboratory of the University Physiology Institute.
      DESIGN: Prospective observational study. INTERVENTIONS: Studies were performed in
      conscious sheep after unilateral nephrectomy with a vascular occluder and flow
      probe implanted on the remaining renal artery. In five sheep, renal blood flow
      (RBF) was reduced by 25, 50 and 75%, respectively, by acute vascular occlusion
      for 30 min at weekly intervals. In another six sheep, RBF was reduced by 80% for
      2 h. MEASUREMENTS AND RESULTS: After 25, 50 or 75% renal hypoperfusion for 30
      min, there was no associated extended loss of renal function. During 2 h of 80%
      hypoperfusion, urine output decreased from 80 to 17 ml, and creatinine clearance
      from 32 to 3 ml/min, whereas plasma creatinine increased from 103 to 132 mumol/l,
      and fractional excretion of sodium and urea increased. Release of occlusion
      induced brief hyperemia before all measured variables returned to normal within 8
      h and remained normal for the following 72 h. At autopsy, the kidneys were
      histopathologically normal. CONCLUSIONS: Various degrees of renal hypoperfusion
      for 30 min did not induce prolonged changes in renal function or blood flow. Even
      with sustained severe hypoperfusion, there was rapid recovery to baseline
      function and flow. Unlike total ischemia, severe hypoperfusion alone is
      insufficient to induce subsequent persistent AKI.

PMID- 20049588
TI  - Stir-bar-sorptive extraction and liquid desorption combined with large-volume
      injection gas chromatography-mass spectrometry for ultra-trace analysis of musk
      compounds in environmental water matrices.
AB  - Stir-bar-sorptive extraction with liquid desorption followed by large-volume
      injection and capillary gas chromatography coupled to mass spectrometry in
      selected ion monitoring acquisition mode (SBSE-LD/LVI-GC-MS(SIM)) has been
      developed to monitor ultra-traces of four musks (celestolide (ADBI), galaxolide
      (HHCB), tonalide (AHTN) and musk ketone (MK)) in environmental water matrices.
      Instrumental calibration (LVI-GC-MS(SIM)) and experimental conditions that could
      affect the SBSE-LD efficiency are discussed. Assays performed on 30-mL water
      samples spiked at 200 ng L(-1) under optimized experimental conditions yielded
      recoveries ranging from 83.7 +/- 8.1% (MK) to 107.6 +/- 10.8% (HHCB).
      Furthermore, the experimental data were in very good agreement with predicted
      theoretical equilibria described by octanol-water partition coefficients (K
      (PDMS/W) ~ K (O/W)). The methodology also showed excellent linear dynamic ranges
      for the four musks studied, with correlation coefficients higher than 0.9961,
      limits of detection and quantification between 12 and 19 ng L(-1) and between 41
      and 62 ng L(-1), respectively, and suitable precision (< 20%). Application of
      this method for analysis of the musks in real water matrices such as tap, river,
      sea, and urban wastewater samples resulted in convenient selectivity, high
      sensitivity and accuracy using the standard addition methodology. The proposed
      method (SBSE-LD/LVI-GC-MS(SIM)) was shown to be feasible and sensitive, with a
      low-sample volume requirement, for determination of musk compounds in
      environmental water matrices at the ultra-trace level, overcoming several
      disadvantages presented by other sample-preparation techniques.

PMID- 20049589
TI  - Some people and places important in the history of analytical chemistry in
      Austria.

PMID- 20049590
TI  - Minimal RNA aptamer sequences that can inhibit or alleviate noncompetitive
      inhibition of the muscle-type nicotinic acetylcholine receptor.
AB  - Combinatorially synthesized nucleotide polymers have been used during the last
      decade to find ligands that bind to specific sites on biological molecules,
      including membrane-bound proteins such as the nicotinic acetylcholine receptors
      (nAChRs). The neurotransmitter receptors belong to a group of four structurally
      related proteins that regulate signal transmission between ~10(11) neurons of the
      mammalian nervous system. The nAChRs are inhibited by compounds such as the
      anticonvulsant MK-801 [(+)-dizocilpine] and abused drugs such as cocaine. Based
      on predictions arising from the mechanism of receptor inhibition by MK-801 and
      cocaine, we developed two classes of RNA aptamers: class I members, which inhibit
      the nAChR, and class II members, which alleviate inhibition of the receptor by MK
      801 and cocaine. The systematic evolution of ligands by the exponential
      enrichment (SELEX) method was used to obtain these compounds. Here, we report
      that we have truncated RNA aptamers in each class to determine the minimal
      nucleic acid sequence that retains the characteristic function for which the
      aptamer was originally selected. We demonstrate that a truncated class I aptamer
      containing a sequence of seven nucleotides inhibits the nAChR and that a
      truncated class II aptamer containing a sequence of only four nucleotides can
      alleviate MK-801 inhibition.

PMID- 20049591
TI  - Highly polar environments catalyze the unfolding of PrP C helix 1.
AB  - The first alpha-helix (H1) likely plays an important role in the conversion of
      the cellular prion protein (PrP(C)) into its pathogenic isoform (PrP(Sc)). In
      this conversion, H1 may either have to unfold or may represent a site of
      intermolecular contact. A recent molecular dynamics simulation suggested that H1
      can unfold if it is detached from the protein core (Hirschberger et al. in
      Biophys J 90:3908, 2006). It has been hypothesized that the high dielectric
      constant epsilon (S) of the bulk water environment facilitates the unfolding of
      H1. To check this hypothesis, we performed a number of replica exchange molecular
      dynamics simulations of an H1 peptide in solvents of different epsilon (S). We
      found that the equilibrium helix fraction in water is less than 40%, in agreement
      with previous experimental findings, and that the helix unfolds much faster in
      water than in less polar solvents. The kinetically stabilizing effect of the
      organic solvents is largely unspecific and correlates well with their dielectric
      constant epsilon (S).

PMID- 20049592
TI  - Bilateral, symmetrical soft tissue calcifications in the face.
AB  - A 50-year-old woman with jaw pain and a history of bisphosphonate use was shown
      on radiography to have ill-defined soft tissue calcifications overlying the
      maxilla, mandible, and zygomatic bones bilaterally. The bones were normal. CT
      revealed similar findings. Although a broad imaging differential diagnosis was
      initially considered, further questioning of the patient revealed a history of
      facial injections with a calcium hydroxylapatite product for cosmetic purposes.
      The appearance of this increasingly popular treatment should be recognized to
      avoid errors in interpretation.

PMID- 20049593
TI  - The periosteum: what is it, where is it, and what mimics it in its absence?
AB  - Nearly every bone in the body is invested in periosteum. The periosteum is in
      some ways poorly understood and has been a subject of controversy and debate.
      This tissue has a major role in bone growth and bone repair and has an impact on
      the blood supply of bone as well as skeletal muscle. Despite the importance of
      the periosteum is has received little attention in the literature in recent
      years.

PMID- 20049594
TI  - Patients with life-threatening arterial renal hemorrhage: CT angiography and
      catheter angiography with subsequent superselective embolization.
AB  - The purpose of this study was to evaluate the technical and clinical success of
      superselective embolization in patients with life-threatening arterial renal
      hemorrhage undergoing preinterventional CT angiography. Forty-three patients with
      clinical signs of life-threatening arterial renal hemorrhage underwent CT
      angiography and catheter angiography. Superselective embolization was indicated
      in the case of a positive catheter angiography. Primary study goals were
      technical and clinical success of superselective embolization. Secondary study
      goals were CT angiographic and catheter angiographic image findings and clinical
      follow-up. The mean time interval between CT angiography and catheter angiography
      was 8.3 +/- 10.3 h (range, 0.2-34.1 h). Arterial renal hemorrhage was identified
      with CT angiography in 42 of 43 patients (98%) and catheter angiography in 39 of
      43 patients (91%) (overview angiography in 4 of 43 patients [9%], selective
      angiography in 16 of 43 patients [37%], and superselective angiography in 39 of
      43 patients [91%]). Superselective embolization was performed in 39 of 43
      patients (91%) and technically successful in 37 of 39 patients (95%). Therefore,
      coil embolization was performed in 13 of 37 patients (35%), liquid embolization
      in 9 of 37 patients (24%), particulate embolization in 1 of 37 patients (3%), and
      a combination in 14 of 37 patients (38%). Clinical failure occurred in 8 of 39
      patients (21%) and procedure-related complications in 2 of 39 patients (5%). The
      30-day mortality rate was 3%. Hemoglobin decreased significantly prior to
      intervention (P < 0.001) and increased significantly after intervention (P <
      0.005). In conclusion, superselective embolization is effective, reliable, and
      safe in patients with life-threatening arterial renal hemorrhage. In contrast to
      overview and selective angiography, only superselective angiography allows
      reliable detection of arterial renal hemorrhage. Preinterventional CT angiography
      is excellent for detection and localization of arterial renal hemorrhage and
      appropriate for guidance of the embolization procedure.

PMID- 20049595
TI  - Endograft collapse after endovascular treatment for thoracic aortic disease.
AB  - Endovascular treatment is an established therapy for thoracic aortic disease.
      Collapse of the endograft is a potentially fatal complication. We reviewed 16
      patients with a thoracic endograft between 2001 and 2006. Medical records of the
      treated patients were studied. Data collected include age, gender, diagnosis,
      indication for endoluminal treatment, type of endograft, and time of follow up.
      All patients (n = 16; mean age, 61 years; range, 21-82 years) underwent computed
      tomography (CT) for location of the lesion and planning of the intervention. Time
      of follow-up with CT scan ranged from 1 to 61 months. Indications for
      endovascular treatment were degenerative aneurysm (n = 7; 44%), aortic dissection
      (n = 2; 12%), perforated aortic ulcer (n = 4; 25%), and traumatic aortic injury
      (n = 3; 19%). Three patients suffered from a collapse of the endograft (one
      patient distal, two patients proximal) between 3 and 8 days after endovascular
      treatment. These patients were younger (mean age, 37 +/- 25 years vs. 67 +/- 16
      years; P < 0.05) and showed more oversizing (proximal, 36 +/- 19.8% vs. 29 +/-
      20.7% [P > 0.05]; distal, 45 +/- 23.5% vs. 38 +/- 21.7% [P > 0.05]). Proximal
      collapse was corrected by placing a bare stent. In conclusion, risk factors for
      stent-graft collapse are a small lumen of the aorta and a small radius of the
      aortic arch curvature (young patients), as well as oversizing, which is an
      important risk factor and is described for different types of endografts and
      protheses (Gore TAG and Cook Zenith). Dilatation of the collapsed stent-graft is
      not sufficient. Following therapy implantation of a second stent or surgery is
      necessary in patients with a proximal endograft collapse. Distal endograft
      collapse can possibly be treated conservatively under close follow-up.

PMID- 20049596
TI  - An unreported pattern of musculocutaneous and median nerve communication with
      multiple variations of biceps brachii: a case report.
AB  - An unreported pattern of communication between musculocutaneous (Mcn) and median
      nerve (Mn) with multiple variations of biceps brachii (Bb) was observed during
      the dissection of a male cadaver. The first branch of the Mcn ended in
      coracobrachialis (Cb). The second was the main Mcn piercing the Cb and giving its
      motor branches to the muscles of the anterior compartment of the arm. It then
      continued as the lateral cutaneous nerve of the forearm. The largest third branch
      also pierced the Cb distal to the main Mcn and communicated with the Mn which was
      classically formed by relevant roots of the medial and lateral cords.
      Additionally, a third head of Bb was observed bilaterally. Slips from the
      pectoralis major were inserted on the tendon of the third head on both sides. The
      origin of the third head was the greater tubercle to the left and the joint
      capsule to the right. These extremely rare patterns of both variations which were
      seen concomitantly in the same subject do not exist in the literature. Lack of
      awareness of such variations with different patterns of communications between
      Mcn and Mn might complicate surgical repair of the nerves. Knowing different
      patterns of Bb variations also have clinical importance as they also may cause
      compression of neurovascular structures or confuse a surgeon during surgical
      procedures.

PMID- 20049597
TI  - Effect of indole-3-acetic acid (IAA) produced by Pseudomonas aeruginosa in
      suppression of charcoal rot disease of chickpea.
AB  - The production of indole-3-acetic acid (IAA), by rhizobacteria, has been
      associated with plant growth promotion, especially root initiation and
      elongation. Isolate TO3 selected from 103 fluorescent pseudomonads, identified as
      Pseudomonas aeruginosa, showed maximum production of IAA. Isolate TO3 having
      biocontrol activity against Macrophomina phaseolina also showed production of
      siderophore and HCN was used to screen the role of bacterial IAA in reducing the
      level of charcoal rot disease occurrence in chickpea. Four IAA defective stable
      mutants of isolate TO3 having biocontrol activity against M. phaseolina were
      developed through 5-bromouracil mutagenesis. Mutant TO(52) showed 76.47%
      reduction in production of IAA. Standard IAA was used in similar concentration as
      present in cell-free culture supernatant of wild isolate TO3 and its mutant
      TO(52). The in vitro and in vivo study showed that IAA-defective mutant TO(52)
      caused reduced biocontrol and plant growth promotory activity than wild isolate
      TO3. Standard IAA showed comparable biocontrol activity to the culture
      supernatant. To some extent better biocontrol and growth promotory activity in
      supernatant than standard IAA indicates the synergistic role of siderophore and
      HCN. The study clearly reports the role of bacterial IAA in suppression of
      charcoal rot disease of chickpea.

PMID- 20049598
TI  - Dual fluorochrome flow cytometric assessment of yeast viability.
AB  - A novel staining protocol is reported for the assessment of viability in yeast,
      specifically the biocontrol yeast, Pichia anomala. Employing both the red
      fluorescent membrane potential sensitive oxonol stain DiBAC(4)(5) (Bis-(1,3
      dibutylbarbituric acid)pentamethine oxonol), a structural analog of the commonly
      used DiBAC(4)(3) (Bis-(1,3-dibutylbarbituric acid)trimethine oxonol), with one of
      the esterase dependent green fluorogenic probes such as CFDA-AM (5
      Carboxyfluorescein diacetate, acetoxymethyl ester) or Calcein-AM (Calcein
      acetoxymethyl ester), a two-color flow cytometric method was developed, which
      yields rapid quantitative information on the vitality and vigor of yeast cell
      cultures. The method was validated by cell sorting and analysis of live, heat
      killed, and UV-treated yeast.

PMID- 20049599
TI  - Cloning and characterization of a plasmid encoded ACC deaminase from an
      indigenous Pseudomonas fluorescens FY32.
AB  - In addition to the characterized mechanisms responsible for many direct effects
      of plant growth promoting bacteria (PGPB) on plants, it has been suggested that a
      number of PGPB contain the enzyme ACC deaminase that catalyzes degradation of 1
      aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of ethylene,
      into alpha-ketobutyrate and ammonia. As part of an effort to obtain an ACC
      deaminase encoding gene from a collection of soil samples, only one bacterial
      isolate, Pseudomonas fluorescens FY32 was capable of growing on ACC as a sole
      source of nitrogen. The ACC deaminase gene was amplified from the above isolate
      by polymerase chain reaction (PCR) giving an expected DNA fragment, 1017 bp.
      Sequence analysis of the fragment showed that it was highly homologous (94% and
      98% identities at nucleotide and amino acid levels, respectively) to the
      previously characterized acdS gene from Pseudomonas sp. 6G5. Furthermore, fusion
      of the ACC deaminase ORF with lacZ gene resulted in the expression of active
      enzyme in Escherichia coli. In addition, further analyses revealed that the acdS
      gene was plasmid-encoded so that a large plasmid (pFY32) with almost 50 kb in
      size was identified from this bacterium. Furthermore, transfer of pFY32 into E.
      coli DH5alpha proved its ACC deaminase activity. This result was in accordance
      with previous reports suggesting horizontal transfer of the acdS gene. However,
      it needs more investigation to identify whether this pFY32 plasmid has undergone
      lateral gene transfer during the evolutionary process.

PMID- 20049600
TI  - Segmental expression of claudin proteins correlates with tight junction barrier
      properties in rat intestine.
AB  - In tubular epithelia, barrier function varies in a segment-specific way. The aim
      of this study was to correlate the presence of tight junction proteins and
      paracellular barrier properties along rat intestine. Tissue segments of duodenum,
      jejunum, ileum, and colon were stripped of submucosal cell layers and mounted in
      Ussing chambers for impedance spectroscopy to measure epithelial resistance (R
      (epi)). In parallel, expression of tight junction proteins was analysed by
      Western blots and immune fluorescence confocal microscopy. Colon showed highest R
      (epi), followed by duodenum, jejunum, and ileum. In small intestine, common
      transepithelial resistance (R (trans) or TER) overestimated true R (epi) by
      approximately 60%. In colon, strongest expression of "tightening" claudins 1, 3,
      4, 5, and 8 was detected. In accordance with R (epi) the most proximal of the
      small intestinal segments, duodenum exhibited highest expression of "tightening"
      claudins and lowest expression of claudins mediating permeability, namely claudin
      2, -7, and -12, compared to jejunum and ileum. These results correspond to the
      specific role of the duodenum as the first segment facing the acidic gastric
      content.

PMID- 20049601
TI  - Bone remodeling in proximal HA-coated versus uncoated cementless SL-Plus((R))
      femoral components: a 5-year follow-up study.
AB  - BACKGROUND AND PURPOSE: Bone resorption at the femoral stem due to stress
      shielding has been particularly observed secondary to cementless hip replacement.
      This prospective study of 126 total-hip replacements was performed to examine
      clinical outcomes and changes in peri-prosthetic bone density after implantation
      of a double-tapered cementless femoral component manufactured with versus without
      hydroxyapatite (HA) coating. METHODS: Sixty-seven femoral components with and 59
      femoral components without proximal HA coating were implanted and examined after
      a mean follow-up of 5.8 (SD 1.1, 2.8-7.8) years. The Harris hip score (HHS) and
      plain radiographs were used for clinical and radiological follow-up evaluations.
      Possible changes in peri-prosthetic bone mineral density (BMD) were measured by
      dual-energy X-ray absorptiometry (DEXA). RESULTS: Clinical outcome, measured by
      HHS, was similar in both groups. On plain radiographs, significantly less
      radiolucent lines were observed for the coated implants. DEXA revealed a
      significant increase in BMD at the proximal zones, along the medial side, and at
      the stem tips in the coated compared with the non-coated implants.
      INTERPRETATION: Hydroxyapatite-coated implants yield favorable radiographic
      characteristics, but no greater clinical benefit after 5 years' implantation.

PMID- 20049602
TI  - Intraoperative three-dimensional fluoroscopy assessment of iliosacral screws and
      lumbopelvic implants stabilizing fractures of the os sacrum.
AB  - INTRODUCTION: Percutaneous iliosacral screw fixation of unstable sacrum fractures
      has gained popularity since its introduction in the 1990s. The combination with
      lumbopelvic implants allows the application even in situations of higher
      instability. Both manual and navigated screw insertion in the sacrum and vertebra
      bodies shows unchanged relevant malpositions. The current standard to control the
      screw position is postoperative computed tomography. The study presents the
      results of assessment of these implants by intraoperative three-dimensional
      fluoroscopy. METHODS: From January 2008 through March 2009, 14 patients had
      stabilization of the dorsal pelvic ring with iliosacral screws alone or in
      combination with lumbopelvic implants. Intraoperative 3D fluoroscopy was
      performed to evaluate the position of the implants stabilizing the posterior
      pelvic ring. RESULTS: Fourteen iliosacral screws and eight pedicle screws were
      depicted. In all patients, we were able to adequately evaluate the placement of
      iliosacral screws, lumbar pedicle screws and iliacal screws. As a consequence of
      intraoperative 3D scan a lumbar pedicle screw was corrected. The entire scanning
      procedure required 5 min. The time for analyzing the 3D scan took 3 min.
      CONCLUSIONS: Intraoperative 3D fluoroscopy is a valuable tool for intraoperative
      assessment of iliosacral screws and lumbopelvic implants. The technique should
      help us to detect intraoperative malplacement of the screws more reliably than
      conventional fluoroscopy and allows an immediate correction of malplaced
      implants. Therefore, a postoperative computed tomography to control the position
      of implants is dispensable.

PMID- 20049603
TI  - Medical problems in hip fracture patients.
AB  - Increasing number of older patients are admitted to hospital with hip fractures.
      This review evaluates the common medical problems that arise as a consequence of
      having a hip fracture. Older patients with fractures commonly have co-morbidities
      that require evaluation prior to and after surgery. Joint acute orthopaedic
      geriatric units have been established to provide comprehensive orthopaedic and
      medical care with some studies showing a reduction in postoperative complications
      and mortality. Recommendations surrounding the care of the older orthopaedic
      patient include early surgical fixation, the use of prophylactic antibiotics and
      thromboembolic prophylaxis, good perioperative pain control to improve
      ambulation, delirium detection and management to decrease the risk complications,
      such as institutionalisation, the avoidance of malnutrition, urinary tract
      management, osteoporosis management and the promotion of early mobilisation to
      improve functional recovery. Physicians are well placed to manage these patients
      with orthopaedic surgeons during the perioperative period. Sufficient evidence
      exists for most recommendations for fracture patients, but further research is
      needed in most areas.

PMID- 20049604
TI  - Two-dimensional fluoroscopic navigation in posterior cruciate ligament
      reconstruction: a preclinical cadaver study.
AB  - OBJECTIVES: To assess the feasibility and accuracy of frameless stereotactic two
      dimensional fluoroscopy-assisted guide pin (GP) placement in posterior cruciate
      ligament (PCL) reconstruction in human cadavers. MATERIALS AND METHODS: A total
      of 13 pins were placed in 7 cadaver specimens, using a fluoroscopic-based
      navigation technique. The knees were fixed noninvasively on a carbon baseplate.
      Interventions were planned on intraoperatively acquired perpendicular
      fluoroscopic images. A stereotactic aiming device was mounted to the carbon
      baseplate and adjusted according to the planned trajectories. GPs were advanced
      through the aiming device to the precalculated depth. GP positions were verified
      by image fusion of the fluoroscopic planning and control data, respectively.
      Measurements were scored on three occasions by one independent observer. In order
      to assess interobserver reliability, measurements were scored by two further
      independent observers on one occasion. RESULTS: The femoral cohort included seven
      GP placements in seven cadavers. Mean GP placement accuracy according to plan was
      1.3 mm (SD 0.9 mm, range 0.3-3.8 mm) at the target point. The recorded femoral
      angular misalignment of GPs was 1.1 degrees (SD 0.9 degrees , range 0.2 degrees 
      3.3 degrees ). The tibial cohort included six GP placements in six cadavers. Mean
      GP placement accuracy according to the plan was 1.8 mm (SD 2.1 mm, range 0.3-9.5
      mm). The recorded tibial angular misalignment of GPs was 1.4 degrees (SD 1.1
      degrees , range 0.1 degrees -5 degrees ). Navigated GP implantation, as planned,
      was optimal in six out of seven cases in the femoral cohort and in four out of
      six cases in the tibial cohort. CONCLUSION: Our preliminary cadaver study
      suggests that the use of fluoroscopic-based navigation combined with a
      stereotactic targeting device may be a helpful tool to improve PCL
      reconstruction. In addition, this method may also be used for other minimal
      invasive skeletal interventions.

PMID- 20049605
TI  - Initial load-to-failure and failure analysis in single- and double-row repair
      techniques for rotator cuff repair.
AB  - AIM: This experimental study aimed to compare the load-to-failure rate and
      stiffness of single- versus double-row suture techniques for repairing rotator
      cuff lesions using two different suture materials. Additionally, the mode of
      failure of each repair was evaluated. METHOD: In 32 sheep shoulders, a
      standardized tear of the infraspinatus tendon was created. Then, n = 8 specimen
      were randomized to four repair methods: (1) Double-row Anchor Ethibond coupled
      with polyester sutures, USP No. 2; (2) Double-Row Anchor HiFi with polyblend
      polyethylene sutures, USP No. 2; (3) Single-Row Anchor Ethibond coupled with
      braided polyester sutures, USP No. 2; and (4) Single-Row Anchor HiFi with braided
      polyblend polyethylene sutures, USP No. 2. Arthroscopic Mason-Allen stitches were
      placed (single-row) and combined with medial horizontal mattress stitches (double
      row). All specimens were loaded to failure at a constant displacement rate on a
      material testing machine. RESULTS: Group 4 showed lowest load-to-failure result
      with 155.7 +/- 31.1 N compared to group 1 (293.4 +/- 16.1 N) and group 2 (397.7
      +/- 7.4 N) (P < 0.001). Stiffness was highest in group 2 (162 +/- 7.3 N/mm) and
      lowest in group 4 (84.4 +/- 19.9 mm) (P < 0.001). In group 4, the main cause of
      failure was due to the suture cutting through the tendon (n = 6), a failure case
      observed in only n = 1 specimen in group 2 (P < 0.001). CONCLUSIONS: A double-row
      technique combined with arthroscopic Mason-Allen/horizontal mattress stitches
      provides high initial failure strength and may minimize the risk of the
      polyethylene sutures cutting through the tendon in rotator cuff repair when a
      single load force is used.

PMID- 20049606
TI  - Soft stabilization with interspinous artificial ligament for mildly unstable
      lumbar spinal stenosis: a multicenter comparison.
AB  - INTRODUCTION: In an attempt to fill a gap between simple decompression alone and
      fusion in the spectrum of surgical treatment for degenerative lumbar spinal
      stenosis (DLSS), the authors sought to demonstrate the efficacy and
      reproducibility of soft stabilization with interspinous artificial ligament after
      microsurgical fenestration to prevent post-decompression segmental instability
      for mildly unstable DLSS. MATERIALS AND METHODS: Clinical outcomes from 556
      patients treated with soft stabilization with artificial ligament following
      microdecompression for mildly unstable DLSS from March 1998 to June 2006 were
      retrospectively obtained from three institutions in three countries. Outcomes
      were measured at a mean of 48.9 months after surgery using MacNab criteria. Peri-
      and postoperative complications and revision surgery cases were also analyzed.
      RESULTS: Follow-up was achieved in 391 (70.3%) of the 556 patients. Clinical
      outcomes were excellent in 43.7%, good in 36.7%, fair in 12.2%, and poor in 7.4%
      of the patients. The overall clinical success rate was 80.4%. No major
      complications except postoperative hematoma and wound infection (6/391 cases,
      1.5%) were observed, and few revision surgeries (2.3%) were done during follow
      up. CONCLUSION: We found favorable and reproducible results with soft
      stabilization with artificial ligament after microdecompression for mildly
      unstable DLSS from three institutions in three countries. Soft stabilization with
      artificial ligament may be concluded to represent an effective prevention of
      increased post-decompression instability with reliable reproducibility for mildly
      unstable DLSS in carefully selected patients.

PMID- 20049607
TI  - Arthrodesis of the subtalar and talonavicular joints through a medial surgical
      approach: a series of 15 cases.
AB  - INTRODUCTION: We report a series of 15 double-hindfoot (subtalar and
      talonavicular joint) arthrodeses through a single medial approach on 14 patients.
      Mean age at surgery was 59.3 years. The chosen surgical technique was always
      identical using a medial approach and performed by a single surgeon. The average
      follow-up was 20.6 months. METHOD: The mean Kitaoka score increased from 44 to
      75, axis of the hindfoot decreased from 21 degrees to 11 degrees in valgus, arch
      foot angle decreased from 142 degrees to 134.4 degrees . Two failures have led to
      a secondary complementary arthrodesis of the talocrural joint. RESULTS:
      Throughout our study, subtalar and talonavicular arthrodesis in the treatment of
      painful valgus deformities of the hindfoot reveals to be a valuable and safe
      alternative. The chosen fixation method combined with a good articular surface
      avivement through medial approach guarantee a long-term fusion. Moreover, resort
      to a medial approach significantly reduces wound complications. CONCLUSION: This
      medial approach procedure permits the fusion without developing non-union and
      provides a significant correction of the fixed deformities.

PMID- 20049608
TI  - Treatment of fractures of the fifth metatarsal with the XS-nail retrospective
      study and comparison with tension-band wiring.
AB  - INTRODUCTION: Many different surgical methods and implants for the treatment of
      fifth metatarsal fractures have been established yet. A high rate of
      complications, such as nonunion, fragment dislocation, refracture, implant
      deformation and irritation are widely occurring due to the insufficient ability
      of the implants to compensate the tension applied to the proximal fragment
      through the peroneal tendon combined with an impaired blood supply at the
      fracture zone. Therefore, the search for improved surgical solutions is
      thoroughly understandable. Thus, we have introduced the XS-nail as an
      intramedullary nail system that bears the ability to provide a compression to the
      fracture zone through a grub screw. In this work, we have analyzed the position
      of the XS-nail in relationship to other methods with special regard to the
      tension-band wiring. METHOD: In a retrospective analysis, we examined 77 cases,
      where a proximal fifth metatarsal fracture has been treated with the XS-nail. As
      a comparison group, we collected data from 47 patients who had been treated with
      tension-band wiring for the same indication in our hospital. Altogether, we
      included 124 patients, representing the largest study population of surgically
      treated cases of proximal fifth metatarsal fractures as compared to the actual
      literature. RESULTS: When compared with the tension-band wiring group, we found
      in mean a shorter duration of the surgery, a lower necessity of an open reduction
      (18 vs. 100%), fewer postsurgical weight-bearing restrictions (54 vs. 100%) and a
      shorter duration of rehabilitation (48 vs. 71 days). Especially, the fracture
      compression was distinctively higher in the XS-nail group (postsurgical lateral
      dislocation was 0-59%). The advantages of the tension-band wiring were found in
      the fixation of small fragments and an easier implant removal. Generally,
      nonunion and refracture were not seen in both methods. When compared with the
      results from literature, we found positive results regarding the hospitalization
      duration, the weight-bearing ability, the rehabilitation course and the patients'
      satisfaction. CONCLUSION: Thus, the XS-nail proved to be an effective and
      technical optimized implant for the treatment of proximal fifth metatarsal
      fractures that provides a rapid full-weight-bearing mobilization and shows good
      long-term results.

PMID- 20049609
TI  - Fixation of Akin osteotomy for hallux abductus with absorbable suture.
AB  - BACKGROUND: The Akin osteotomy is a widely used procedure where various fixation
      methods are available, predominantly with the use of metallic component (wire,
      screw, staple etc.). The aim of this study is to demonstrate the results of our
      modified Akin procedures, where the fixation of the phalangeal osteotomy is
      achieved by absorbable suture, without metallic component. MATERIALS AND METHODS:
      Between July 2004 and October 2008, authors performed their first 22 consecutive
      Akin procedures with the above technique. Mean age of patients was 49 [standard
      deviation (SD) 17, range 19-69] years. Mean follow-up time was 26 (SD 13, range 8
      57) months. RESULTS: Mean correction of the distal articular set angle (DASA) was
      9.4 (SD 7.1, range 5-28) degrees. Mean shortening of the proximal phalanx was 1.8
      (SD 1.0, range 0.3-4.1) mm. Among the 22 osteotomies, there was no evidence of
      non-union, delayed union, excessive bone callus, or loss of correction. 100% of
      the patients would undergo the procedure again, 91% (20/22) were completely
      satisfied; and 9% (2/22) were satisfied, including the one complication case.
      CONCLUSION: The method presented in this study for fixation of the akin osteotomy
      showed results identical to the ones using conventional (metal) fixation
      techniques concerning radiological (correction of DASA, shortening of the
      proximal phalanx), and clinical (complication rate, subjective satisfaction rate)
      findings, without the risk of complication due to hardware irritation.

PMID- 20049610
TI  - Use of proteomics in radiobiological research: current state of the art.

PMID- 20049611
TI  - Comparative proteomic analysis of longan (Dimocarpus longan Lour.) seed abortion.
AB  - Two-dimensional gel electrophoresis (2-DE), coupled with mass spectroscopy, was
      used to study seed abortion in Dimocarpus longan Lour. (cv. Minjiao 64-1) by
      comparing normal and aborted seeds at three developmental stages. More than 1,000
      protein spots were reproducibly detected in 2-DE gels, with 43 protein spots
      being significantly altered in their intensity between normal and aborted seeds
      at least at one stage. Thirty-five proteins were identified by matrix-assisted
      laser desorption ionization-time of flight-tandem mass spectrometry (MALDI-TOF
      MS/MS) analysis and protein database searching. Most of the identified proteins
      were associated with a variety of functions, including energy and metabolism
      (30%), programed cell death (9%), antioxidative processes (14%), chaperonin
      (23%), cell division, amino acid metabolism, secondary metabolism, and other
      functional classes. Furthermore, the expression patterns of HSP70 and cytosolic
      ascorbate peroxidase (cAPX) were validated by immunoblotting analysis. This study
      provides a novel, global insight into proteomic differences between normal and
      aborted seeds in longan. We anticipate that identification of the differentially
      expressed proteins may lead to a better understanding of the molecular basis for
      seed abortion in longan.

PMID- 20049612
TI  - Cloning and characterization of the Gossypium hirsutum major latex protein gene
      and functional analysis in Arabidopsis thaliana.
AB  - The major latex protein (MLP) gene in Gossypium hirsutum was cloned and
      designated Gh-MLP. Expression in cotton root was induced by salt stress and
      Verticillium dahliae toxin, and bioinformatic analysis showed that Gh-MLP encodes
      a 157-amino acid protein that is similar to members of the MLP subfamily in the
      Bet v 1 family. Although the structure of MLP is similar to Bet v 1 family
      proteins, the sequence identity to other subfamilies of Bet v 1 proteins is less
      than 20%. The Gh-MLP promoter contains potential cis-acting elements for response
      to salt stress and fungal elicitor. RT-PCR analysis showed that Gh-MLP expression
      was rapidly induced by NaCl and V. dahliae toxin, and induction was maintained
      over 72 h. However, Gh-MLP transgenic Arabidopsis thaliana did not show
      resistance to V. dahiae, salt tolerance was significantly enhanced. In contrast
      to the wild type, the Gh-MLP transgene allowed plants to germinate normally after
      treatment with 75 mM NaCl. Total flavonoid was twofold higher in transgenic
      Arabidopsis than in the control, suggesting that Gh-MLP might be involved in
      altering flavonoid content. We hypothesize Gh-MLP, like other Bet v 1 family
      proteins, participates in the binding or transport of ligands through its
      specific three-dimensional structure, and takes part in defensive responses to
      biotic and abiotic stresses.

PMID- 20049613
TI  - Comprehensive analysis of rice DREB2-type genes that encode transcription factors
      involved in the expression of abiotic stress-responsive genes.
AB  - DREB2s (dehydration-responsive element-binding protein 2s) are transcription
      factors that interact with a cis-acting DRE (dehydration-responsive element)/CRT
      (C-repeat) sequence and activate the expression of downstream genes involved in
      water- and heat-shock stress responses and tolerance in Arabidopsis thaliana. In
      this study, we performed a comprehensive analysis of all five DREB2-type genes in
      rice (OsDREB2 s: OsDREB2A, OsDREB2B, OsDREB2C, OsDREB2E and OsABI4) to determine
      which of them contribute to plant stress responses. We analysed the expression
      patterns of these genes under abiotic stress conditions, and we examined the
      subcellular localisation and transcriptional activation activity of their
      translational products in protoplasts. Only OsDREB2A and OsDREB2B showed abiotic
      stress-inducible gene expression. In addition, OsDREB2B showed nuclear specific
      localisation and the highest transactivation activity. OsDREB2B has functional
      and non-functional forms of its transcript similar to its orthologues in the
      grass family, and the functional form of its transcript was markedly increased
      during stress conditions. We analysed the splicing mechanism of OsDREB2B with
      transgenic rice that express the non-functional transcript and we found that the
      non-functional form is not a precursor of the functional form; thus, stress
      inducible alternative splicing of pre-mRNA is an important mechanism for the
      regulation of OsDREB2B. Transgenic Arabidopsis plants overexpressing OsDREB2B
      showed enhanced expression of DREB2A target genes and improved drought and heat
      shock stress tolerance. These results suggest that OsDREB2B is a key gene that
      encodes a stress-inducible DREB2-type transcription factor that functions in
      stress-responsive gene expression in rice.

PMID- 20049614
TI  - Molecular anatomy of the kidney: what have we learned from gene expression and
      functional genomics?
AB  - The discipline of paediatric nephrology encompasses the congenital nephritic
      syndromes, renal dysplasias, neonatal renal tumours, early onset cystic disease,
      tubulopathies and vesicoureteric reflux, all of which arise due to defects in
      normal kidney development. Indeed, congenital anomalies of the kidney and urinary
      tract (CAKUT) represent 20-30% of prenatal anomalies, occurring in 1 in 500
      births. Developmental biologists have studied the anatomical and morphogenetic
      processes involved in kidney development for the last five decades. However, with
      the advent of transgenic mice, the sequencing of the genome, improvements in
      mutation detection and the advent of functional genomics, our understanding of
      the molecular basis of kidney development has grown significantly. Here we
      discuss how the advent of new genetic and genomics approaches has added to our
      understanding of kidney development and paediatric renal disease, as well as
      identifying areas in which we are still lacking knowledge.

PMID- 20049616
TI  - Single infusion of rituximab for persistent steroid-dependent minimal-change
      nephrotic syndrome after long-term cyclosporine.
AB  - Rituximab (RTX) has been successfully used as a rescue therapy in children with
      steroid-dependent nephrotic syndrome (SDNS). However, little is known regarding
      maintenance therapy after a successful response to RTX in such patients. The
      efficacy and safety of a single RTX infusion (375 mg/m(2)) were assessed in ten
      patients who had persistent SDNS associated with minimal-change disease (MCD)
      despite the long-term use of cyclosporine (CsA). The mean follow-up after RTX
      infusion was 17 months. Applying RTX resulted in a significant reduction in the
      mean prednisolone (PSL) dose from 0.39 +/-0.18 to 0.15 +/- 0.14 mg/kg per day.
      The mean 12-month relapse rates significantly decreased from 4.1 +/- 1.7 to 0.6
      +/- 0.6. All but one patient who had continued CsA as maintenance therapy after a
      single RTX infusion were able to withdraw from PSL without any relapses during
      the study period, whereas the remaining five patients who discontinued CsA
      experienced relapses after CD19 cells re-emerged, leading to the reintroduction
      of CsA or an additional RTX infusion. Infusion reactions occurred in five of ten
      patients. These data indicate that a single RTX infusion may improve response to
      CsA in patients with persistent SDNS due to the phenomenon of secondary
      resistance to CsA.

PMID- 20049617
TI  - The influence of arbuscular mycorrhizal colonization on soil-root hydraulic
      conductance in Agrostis stolonifera L. under two water regimes.
AB  - The hypothesis that mycorrhizal colonization improves the soil-root conductance
      in plants was experimentally tested in a growth chamber using pot cultures of
      Agrostis stolonifera L. colonized by Glomus intraradices. Plants were grown in 50
      l pots filled with autoclaved sand/silt soil (1:1), with and without the
      mycorrhizal fungus. Within the mycorrhizal treatment, half of the pots remained
      well watered, while the other half was subjected to a progressive water deficit.
      Soil water potential (estimated as plant water potential measured at the end of
      the dark period), xylem water potential measured at the tiller base,
      transpiration rate, and soil water content were monitored throughout the
      experiment. Soil-root hydraulic conductance was estimated as the ratio between
      the instantaneous transpiration rate and the soil and xylem water potential
      difference. To obtain cultures with similar nutritional status, the P in the
      modified Hoagland's nutrient solution was withheld from the inoculated pots and
      applied only once a month. Even though there were no differences on growth or
      nutrient status for the mycorrhizal treatments, water transport was enhanced by
      the inoculum presence. Transpiration rate was maintained at lower xylem water
      potential values in the presence of mycorrhizae. The analysis of the relationship
      between soil-root hydraulic resistance and soil water content showed that
      mycorrhizal colonization increased soil-root hydraulic conductance as the soil
      dried. For these growing conditions, this effect was ascribed to the range of 6
      10%.

PMID- 20049615
TI  - Proteinuria and events beyond the slit.
AB  - The origin of proteinuria is found in either the glomerular filtration device or
      the proximal tubular reabsorption machinery. During equilibrium, small amounts of
      predominantly low molecular weight proteins are filtered and reabsorbed by the
      receptor complex megalin/cubilin/amnionless. This results in a protein-free
      filtrate passing further down the tubule. During glomerular damage, the
      reabsorption machinery in the proximal tubule is challenged due to elevated
      amounts of proteins passing the glomerular filtration slits. Even though it is
      considered to be a high-capacity system, several conditions result in
      proteinuria, thus exposing the cells in the rest of the nephron to a protein-rich
      environment. The impact on cells in the more distal part of the nephron is
      uncertain, but studies support an involvement in fibrosis development. Protein
      accumulation in lysosomes of the proximal tubule, due to increased protein
      internalization, is thought to mediate inflammation and fibrosis, eventually
      leading to renal failure. In contrast, low molecular weight proteinuria develops
      when the endocytic machinery is malfunctioning either by direct or indirect
      causes such as in Imerslund-Grasbeck syndrome (IGS) or Dent's disease,
      respectively. This review discusses the origin of proteinuria and describes the
      structural fundament for protein reabsorption in the proximal tubule as well as
      conditions resulting in low molecular weight proteinuria.

PMID- 20049618
TI  - Characterization of a Taura syndrome virus isolate originating from the 2004
      Texas epizootic in cultured shrimp.
AB  - A comprehensive investigation of the Taura syndrome virus (TSV) isolate that
      caused epizootics in shrimp farms in Texas in 2004 (Texas isolate) revealed that
      this virus was more virulent in laboratory bioassays than the TSV reference
      isolate, Hawaii 1994, causing severe symptom development and rapid mortality.
      Histopathology of moribund animals demonstrated epithelial necrosis within the
      stomach, appendages, general body cuticle and gills, and the surviving animals
      demonstrated moderate to numerous lymphoid organ spheroids. Purified virions
      showed icosahedral morphology, with a diameter of 31 nm. Comparative genome
      analysis showed that the Texas isolate is more closely related to TSV isolates
      from Thailand and China than to the Hawaii isolate. The predicted tertiary
      structures of the inhibition of apoptosis protein (IAP) and protease domains of
      the Texas isolate are very similar to those of the Hawaii isolate. However, the
      RNA-dependent RNA polymerase (RdRp) of the Texas isolate has significant
      structural differences from the Hawaii isolate due to point mutation(s) in the
      RdRp gene. Changes in the RdRp tertiary structure might contribute to the
      replication fidelity, virulence and ecological adaptability of the Texas isolate.

PMID- 20049619
TI  - Lack of heterogeneity of HPV16 E7 sequence compared with HPV31 and HPV73 may be
      related to its unique carcinogenic properties.
AB  - To assess the role of human papillomavirus virus (HPV) genetics in cervical
      lesions, we sequenced the E7 gene of HPV16, 31, or 73 from singly infected women
      who (1) cleared the infection quickly, (2) had type-specific persistent
      infection, or (3) progressed to CIN2 or worse lesions. Four of the 296 HPV16 E7
      nucleotides were variable, compared with 7 of 296 for HPV31 E7 and 4 of 296 for
      HPV73 E7. While most of the polymorphisms in HPV31 and -73 resulted in non
      synonymous amino acid changes, the polymorphisms in the HPV16 E7 resulted in
      synonymous changes. The lack of heterogeneity of HPV16 E7 suggests high
      evolutionary purifying selection that might be related to the unique
      carcinogenicity of HPV16.

PMID- 20049621
TI  - Coincident chronic inflammatory demyelinating polyneuropathy and focal segmental
      glomerulosclerosis: a common autoimmunity?
AB  - A 40-year-old male developed swallowing difficulties, loss of strength, and
      imbalance. On admission, the patient exhibited bifacial, extremity weakness,
      ataxia, impaired sensation, and areflexia. Electrophysiology and nerve biopsy
      suggested demyelination. Spinal fluid revealed increased protein content.
      Plasmapheresis showed benefit, but neuropathy relapsed. At second recurrence,
      urine analysis showed heavy proteinuria. Renal biopsy revealed focal segmental
      glomerulosclerosis (FSGS). Methylprednisolone and oral cyclophosphamide were
      given. Long-term steroids and immunoglobulin showed steady benefit. Concurrence
      of chronic inflammatory demyelinating polyneuropathy and FSGS suggests
      synergistic cellular and humoral autoimmune mechanisms related to either cross
      reactivity within antigenic targets or mimicry between neural and renal epitopes.

PMID- 20049620
TI  - Biochemical characterization of a recombinant short-chain NAD(H)-dependent
      dehydrogenase/reductase from Sulfolobus acidocaldarius.
AB  - The gene encoding a novel alcohol dehydrogenase that belongs to the short-chain
      dehydrogenases/reductases (SDRs) superfamily was identified in the aerobic
      thermoacidophilic crenarchaeon Sulfolobus acidocaldarius strain DSM 639. The
      saadh gene was heterologously overexpressed in Escherichia coli, and the protein
      (SaADH) was purified to homogeneity and characterized. SaADH is a tetrameric
      enzyme consisting of identical 28,978-Da subunits, each composed of 264 amino
      acids. The enzyme has remarkable thermophilicity and thermal stability,
      displaying activity at temperatures up to 75 degrees C and a 30-min half
      inactivation temperature of ~90 degrees C, and shows good tolerance to common
      organic solvents. SaADH has a strict requirement for NAD(H) as the coenzyme, and
      displays a preference for the reduction of alicyclic, bicyclic and aromatic
      ketones and alpha-keto esters, but is poorly active on aliphatic, cyclic and
      aromatic alcohols, and shows no activity on aldehydes. The enzyme catalyses the
      reduction of alpha-methyl and alpha-ethyl benzoylformate, and methyl o
      chlorobenzoylformate with 100% conversion to methyl (S)-mandelate [17%
      enantiomeric excess (ee)], ethyl (R)-mandelate (50% ee), and methyl (R)-o
      chloromandelate (72% ee), respectively, with an efficient in situ NADH-recycling
      system which involves glucose and a thermophilic glucose dehydrogenase. This
      study provides further evidence supporting the critical role of the D37 residue
      in discriminating NAD(H) from NAD(P)H in members of the SDR superfamily.

PMID- 20049622
TI  - Renal disease in AIDS: it is not always HIVAN.
AB  - Human immunodeficiency virus (HIV) infection can cause a broad spectrum of
      clinical manifestations, ranging from an asymptomatic carrier state to severe
      immunodeficiency. The most common renal lesion, HIV-associated nephropathy
      (HIVAN), is a sclerosing glomerulopathy. However, potentially reversible causes
      of renal disease in HIV-infected patients should also be considered. We describe
      two cases of patients with acquired immune-deficiency syndrome (AIDS) who
      presented with rapidly progressive renal failure but were found to have
      reversible etiologies. The first case was found to have syphilis and the second,
      disseminated histoplasmosis; their renal injury resolved after initiation of a
      third-generation cephalosporin antibiotic and amphotericin B, respectively.

PMID- 20049623
TI  - Anatomically anchored template-based level set segmentation: application to
      quadriceps muscles in MR images from the Osteoarthritis Initiative.
AB  - In this paper, we present a semi-automated segmentation method for magnetic
      resonance images of the quadriceps muscles. Our method uses an anatomically
      anchored, template-based initialization of the level set-based segmentation
      approach. The method only requires the input of a single point from the user
      inside the rectus femoris. The templates are quantitatively selected from a set
      of images based on modes in the patient population, namely, sex and body type.
      For a given image to be segmented, a template is selected based on the smallest
      Kullback-Leibler divergence between the histograms of that image and the set of
      templates. The chosen template is then employed as an initialization for a level
      set segmentation, which captures individual anatomical variations in the image to
      be segmented. Images from 103 subjects were analyzed using the developed method.
      The algorithm was trained on a randomly selected subset of 50 subjects (25 men
      and 25 women) and tested on the remaining 53 subjects. The performance of the
      algorithm on the test set was compared against the ground truth using the
      Zijdenbos similarity index (ZSI). The average ZSI means and standard deviations
      against two different manual readers were as follows: rectus femoris, 0.78 +/-
      0.12; vastus intermedius, 0.79 +/- 0.10; vastus lateralis, 0.82 +/- 0.08; and
      vastus medialis, 0.69 +/- 0.16.

PMID- 20049624
TI  - Computer input devices: neutral party or source of significant error in manual
      lesion segmentation?
AB  - Lesion segmentation involves outlining the contour of an abnormality on an image
      to distinguish boundaries between normal and abnormal tissue and is essential to
      track malignant and benign disease in medical imaging for clinical, research, and
      treatment purposes. A laser optical mouse and a graphics tablet were used by
      radiologists to segment 12 simulated reference lesions per subject in two groups
      (one group comprised three lesion morphologies in two sizes, one for each input
      device for each device two sets of six, composed of three morphologies in two
      sizes each). Time for segmentation was recorded. Subjects completed an opinion
      survey following segmentation. Error in contour segmentation was calculated using
      root mean square error. Error in area of segmentation was calculated compared to
      the reference lesion. 11 radiologists segmented a total of 132 simulated lesions.
      Overall error in contour segmentation was less with the graphics tablet than with
      the mouse (P < 0.0001). Error in area of segmentation was not significantly
      different between the tablet and the mouse (P = 0.62). Time for segmentation was
      less with the tablet than the mouse (P = 0.011). All subjects preferred the
      graphics tablet for future segmentation (P = 0.011) and felt subjectively that
      the tablet was faster, easier, and more accurate (P = 0.0005). For purposes in
      which accuracy in contour of lesion segmentation is of the greater importance,
      the graphics tablet is superior to the mouse in accuracy with a small speed
      benefit. For purposes in which accuracy of area of lesion segmentation is of
      greater importance, the graphics tablet and mouse are equally accurate.

PMID- 20049625
TI  - Applications of membrane techniques for purification of natural products.
AB  - The recent development of various membrane-based techniques for the purification
      of valuable natural products is reviewed and covers the important research that
      has been conducted in the last 5 years on the utilization of microfiltration,
      ultrafiltration and nanofiltration techniques, either carried out on their own or
      coupled with other separation techniques, in order to achieve concentration and
      purification of natural products from their biological source. There is also a
      special focus on the research that has been undertaken to overcome the membrane
      fouling encountered in their usage.

PMID- 20049627
TI  - Biochemical characterization of soluble nucleotide
      pyrophosphatase/phosphodiesterase activity in rat serum.
AB  - Biochemical properties of nucleotide pyrophosphatase/phosphodiesterase (NPP) in
      rat serum have been described by assessing its nucleotide phosphodiesterase
      activity, using p-nitrophenyl-5'-thymidine monophosphate (p-Nph-5'-TMP) as a
      substrate. It was demonstrated that NPP activity shares some typical
      characteristics described for other soluble NPP, such as divalent cation
      dependence, strong alkaline pH optimum (pH 10.5), inhibition by
      glycosaminoglycans, and K (m) for p-Nph-5'-TMP hydrolysis of 61.8 +/- 5.2 microM.
      In order to characterize the relation between phosphodiesterase and
      pyrophosphatase activities of NPP, we have analyzed the effects of different
      natural nucleotides and nucleotide analogs. ATP, ADP, and AMP competitively
      inhibited p-Nph-5'-TMP hydrolysis with K (i) values ranging 13-43 microM.
      Nucleotide analogs, alpha,beta-metATP, BzATP, 2-MeSATP, and dialATP behaved as
      competitive inhibitors, whereas alpha,beta-metADP induced mixed inhibition, with
      K (i) ranging from 2 to 20 microM. Chromatographic analysis revealed that
      alpha,beta-metATP, BzATP, and 2-MeSATP were catalytically degraded in the serum,
      whereas dialATP and alpha,beta-metADP resisted hydrolysis, implying that the
      former act as substrates and the latter as true competitive inhibitors of serum
      NPP activity. Since NPP activity is involved in generation, breakdown, and
      recycling of extracellular adenine nucleotides in the vascular compartment, the
      results suggest that both hydrolyzable and non-hydrolyzable nucleotide analogs
      could alter the amplitude and direction of ATP actions and could have potential
      therapeutic application.

PMID- 20049626
TI  - Regulating A549 cells growth by ASO inhibiting miRNA expression.
AB  - MicroRNAs (miRNAs) have a profound impact on cell processes, including
      proliferation, apoptosis, and stress responses. We aimed to explore the role of
      antisense oligonucleotide (ASO) to induce proliferation or apoptosis of A549
      cancer cells by inhibiting the expression of miRNAs. After A549/HBE/293T cells
      were treated with ASO, cells proliferation/apoptosis, and their relevant
      oncogenes/tumor suppressor genes were detected by light and electron microscopy,
      real-time PCR, enzyme-linked immunosorbent assay, etc. The results showed that
      ASO could inhibit the expression of miRNAs effectively. miR-16, miR-17, miR-34a
      c, and miR-125 served as tumor suppressor miRNAs, while miR-20, miR-106, and miR
      150 acted as oncogenic miRNAs. Our results also indicated that miR-16/34a-c, miR
      17-5p, miR-125, miR-106, and miR-150 were the upstream factors, which could
      regulate the expression of BCL-2, E2F1, E2F3, RB1, and P53, respectively. After
      A549 cells treated with ASO for 24 h and different concentrations of anti-cancer
      drug (cisplatin or demethylcantharidin) were added into culture medium, the
      results indicated the percentage of alive cells in group treated with both ASO
      106 (or ASO-150) and anti-cancer drug was lower than that in group treated with
      ASO, or anti-cancer drug, or both ASO-16 (or ASO-34a) and anti-cancer drug. In
      conclusion, ASO (specific to oncogenic miRNAs) could induce A549 cells apoptosis
      by inhibiting oncogenic miRNAs, and could increase chemotherapy sensitivity of
      A549 cells to anti-cancer drug, which holds great promise to lung cancer therapy.

PMID- 20049628
TI  - Time-dependent alterations of cerebral proteins following short-term normobaric
      hyperoxia.
AB  - Sufficient oxygenation is indispensable for cognitive performance in mammals. In
      order to assure adequate oxygenation and to prevent hypoxia in medicine or
      aviation, different approaches of oxygen delivery are realized. With regard to
      hyperoxia, it is well known that it increases the risk of tissue toxicity and
      inflammation by generating radical oxygen species. However, this impact of
      hyperoxia on the expression of specific brain proteins has not been evaluated in
      detail yet. The present study analyzes time-dependent changes in protein
      expression in rat brain after a short-term exposure to normobaric hyperoxia.
      Thirty-six Wistar rats were randomly assigned to six different groups, three
      normobaric hyperoxia (NH) groups or three normobaric normoxia (NN) groups, each
      consisting of n = 6 animals. NH animals were exposed to 100% oxygen, NN rats to
      21% oxygen, each group for 3 h. One group of NH and one group of NN were killed
      immediately after the 3 h, one group each after 3 days and one group each after 7
      days. Rat brains were removed for analysis and whole brain detergent protein
      lysates were separated via two-dimensional gel electrophoresis followed by
      subsequent identification of protein expression alterations by peptide mass
      fingerprinting using mass spectrometry. Also, a functional network mapping and
      molecular pathway analysis were carried out. Statistical analysis was performed
      using analysis of variance (ANOVA) with Bonferroni correction using P < 0.01.
      Physiological parameters of the animals did not differ significantly between the
      two groups except for partial oxygen pressure (580 vs. 89 mmHg; P < 0.05). The
      expression of nine proteins was found to be significantly altered (five up
      regulated: GOT1, CCT2, TCP1, G6PD, and ALB; four down-regulated: PEBP1, PRDX2,
      ENO1, and MDH1). IPA generated a network with eight focus proteins associated
      with pathways in "cell death, cancer, and signalling". Although hyperoxia was
      normobaric and induced for only 3 h, significant changes in brain protein
      expression were detectable immediately after the 3 h, after 3 days, as well as
      after 7 days. This may indicate effects on brain protein expression take place in
      the rat brain following a relatively short period of hyperoxia.

PMID- 20049629
TI  - Analysis of GSTM1 and GSTT1 polymorphisms in circulating plasma DNA of lung
      cancer patients.
AB  - The concentration of free circulating plasma DNA and the genetic profile of
      patients suffering from various types of tumors were studied in an effort to
      increase the understanding of the biomarkers and genetic factors involved in
      predisposing an individual to lung cancer (LC). The polymorphic inheritance of
      glutathione S-transferases (GST), which modulate the effects of various genotoxic
      agents, especially those derived from benzo[a]pyrene, one of the main tobacco
      carcinogens, has been implicated in both cancer risk and prognostics. We
      investigated gene polymorphisms in the blood serum of patients previously
      diagnosed at the Pneumology Division of the Clementino Fraga Filho University
      Hospital of the Federal University of Rio de Janeiro and in buccal swab samples
      of exfoliated oral cells obtained from a population of healthy controls. The
      distribution of GSTM1 and GSTT1 polymorphisms was not significantly different
      between LC patients and the controls, suggesting that GSTM1 and GSTT1 alone or in
      combination are not independent risk factors for LC. However, a close
      relationship between smoking status and LC was clearly demonstrated. The most
      significant risk for LC concerning tobacco smoking was found in the association
      of null genotypes for GSTM1 and GSTT1 (P < 0.0001).

PMID- 20049631
TI  - Effects of membrane depolarization and changes in extracellular [K(+)] on the Ca
      (2+) transients of fast skeletal muscle fibers. Implications for muscle fatigue.
AB  - Repetitive activation of skeletal muscle fibers leads to a reduced transmembrane
      K(+) gradient. The resulting membrane depolarization has been proposed to play a
      major role in the onset of muscle fatigue. Nevertheless, raising the
      extracellular K(+) K(+)(O) concentration ([K(+)](O)) to 10 mM potentiates twitch
      force of rested amphibian and mammalian fibers. We used a double Vaseline gap
      method to simultaneously record action potentials (AP) and Ca(2+) transients from
      rested frog fibers activated by single and tetanic stimulation (10 pulses, 100
      Hz) at various [K(+)](O) and membrane potentials. Depolarization resulting from
      current injection or raised [K(+](O) produced an increase in the resting
      [Ca(2+)]. Ca(2+) transients elicited by single stimulation were potentiated by
      depolarization from -80 to -60 mV but markedly depressed by further
      depolarization. Potentiation was inversely correlated with a reduction in the
      amplitude, overshoot and duration of APs. Similar effects were found for the
      Ca(2+) transients elicited by the first pulse of 100 Hz trains. Depression or
      block of Ca(2+) transient in response to the 2nd to 10th pulses of 100 Hz trains
      was observed at smaller depolarizations as compared to that seen when using
      single stimulation. Changes in Ca(2+) transients along the trains were associated
      with impaired or abortive APs. Raising [K(+)](O) to 10 mM potentiated Ca(2+)
      transients elicited by single and tetanic stimulation, while raising [K(+)](O) to
      15 mM markedly depressed both responses. The effects of 10 mM K(+)(O) on Ca(2+)
      transients, but not those of 15 mM K(+)(O), could be fully reversed by
      hyperpolarization. The results suggests that the force potentiating effects of 10
      mM K(+)(O) might be mediated by depolarization dependent changes in resting
      [Ca(2+)] and Ca(2+) release, and that additional mechanisms might be involved in
      the effects of 15 mM K(+)(O) on force generation.

PMID- 20049632
TI  - Affective modulation of the startle eyeblink and postauricular reflexes in autism
      spectrum disorder.
AB  - Eyeblink and postauricular reflexes to standardized affective images were
      examined in individuals without (n = 37) and with (n = 20) autism spectrum
      disorders (ASDs). Affective reflex modulation in control participants replicated
      previous findings. The ASD group, however, showed anomalous reflex modulation
      patterns, despite similar self-report ratings of pictures. Specifically, the ASD
      group demonstrated exaggerated eyeblink responses to pleasant images and
      exaggerated postauricular responses to unpleasant images. Although ASD is often
      conceptualized in terms of specific deficits in affective responding in the
      social domain, the present results suggest a domain-general pattern of deficits
      in affective processing and that such deficits may arise at an early phase in the
      stream of information processing.

PMID- 20049633
TI  - 'Autistic' local processing bias also found in children gifted in realistic
      drawing.
AB  - We investigated whether typically-developing children with a gift for drawing
      realistically show the local processing bias seen in individuals with autism
      spectrum disorder (ASD). Twenty-seven 6-12 year-olds made an observational
      drawing (scored for level of realism) and completed three local processing tasks,
      and parents completed the Childhood Asperger Syndrome Test (CAST). Drawing score
      predicted local processing performance on all tasks independently of verbal IQ,
      age, and years of art lessons. Drawing score also predicted more frequent
      repetitive behaviors as assessed by the CAST. Thus, skill in realistic drawing is
      associated with a strong local processing bias and a tendency towards repetitive
      behaviors, showing that traits found in individuals with ASD irrespective of
      artistic talent are also found in typically developing children with artistic
      talent.

PMID- 20049635
TI  - Hematocrit and plasma osmolality values of young-of-year shortnose sturgeon
      following acute exposures to combinations of salinity and temperature.
AB  - Little is known about the physiological capabilities of young-of-year (YOY)
      shortnose sturgeon. In this study, plasma osmolality and hematocrit values were
      measured for YOY shortnose sturgeon following 48-h exposures to 12 different
      combinations of salinity and temperature. Hematocrit levels varied significantly
      with temperature and age, and plasma osmolalities varied significantly with
      salinity and age. Plasma osmolality and hematocrit values were similar to
      previously published values for other sturgeons of similar age and size in
      similar treatment conditions.

PMID- 20049636
TI  - BMP-2/PLGA delayed-release microspheres composite graft, selection of bone
      particulate diameters, and prevention of aseptic inflammation for bone tissue
      engineering.
AB  - Autogenous bone grafts are widely used in the repair of bone defects. Growth
      factors such as bone morphogenetic protein 2 (BMP-2) can induce bone regeneration
      and enhance bone growth. The combination of an autogenous bone graft and BMP-2
      may provide a better osteogenic effect than either treatment alone, but BMP-2 is
      easily inactivated in body fluid. The objective of this study was to develop a
      technique that can better preserve the in vivo activity of BMP-2 incorporated in
      bone grafts. In this study, we first prepared BMP-2/poly(lactic-co-glycolic acid)
      (PLGA) delayed-release microspheres, and then combined collagen, the delayed
      release microspheres, and rat autologous bone particulates to form four groups of
      composite grafts with different combinations: collagen in group A; collagen
      combined with bone particulates in group B; collagen combined with BMP-2/PLGA
      delayed-release microspheres in group C; and collagen combined with both bone
      particulates and BMP-2/PLGA delayed-release microspheres in group D. The four
      groups of composite grafts were implanted into the gluteus maximus pockets in
      rats. The ectopic osteogenesis and ALP level in group D (experimental group) were
      compared with those in groups A, B, and C (control groups) to study whether it
      had higher osteogenic capability. Results showed that the composite graft design
      increased the utility of BMP-2 and reduced the required dose of BMP-2 and volume
      of autologous bone. The selection of bone particulate diameter had an impact on
      the osteogenetic potential of bone grafts. Collagen prevented the occurrence of
      aseptic inflammation and improved the osteoinductivity of BMP-2. These results
      showed that this composite graft design is effective and feasible for use in bone
      repair.

PMID- 20049634
TI  - Oral health and risk for head and neck squamous cell carcinoma: the Carolina Head
      and Neck Cancer Study.
AB  - OBJECTIVE: Recent reports have linked oral health and periodontal disease
      indicators with increased risk of squamous cell carcinoma of head and neck
      (SCCHN). Thus far, evidence has been inconclusive; our objective was to study the
      association between oral health and SCCHN risk in the context of a large
      population-based study. METHODS: A population-based case-control study of
      incident SCCHN, the Carolina Head and Neck Cancer Study was carried out in 2002
      2006 in 46 counties in North Carolina. Controls (n = 1,361) were frequency
      matched with cases (n = 1,289) on age, race, and gender. Oral health was assessed
      using interview data on tooth loss and mobility, mouthwash use, and frequency of
      dental visits. RESULTS: Subjects were 26-80 years old (median age = 61). The
      distribution of tooth loss among controls was 0-5 teeth = 60%; 5-14 = 15%; and 16
      28 = 25%. After controlling for covariates, tooth loss did not yield any notable
      association with SCCHN (16-28 vs. 0-5 lost teeth: OR: 1.21, 95% CI: 0.94, 1.56).
      Self-reported history of tooth mobility was moderately associated with increased
      SCCHN risk (OR: 1.33, 95% CI: 1.07, 1.65); however, the association did not
      persist among never smokers. Routine dental visits were associated with 30% risk
      reduction (OR: 0.68, 95% CI: 0.53, 0.87). CONCLUSIONS: These data provide support
      for a possible modest association of periodontal disease, as measured by self
      reported tooth loss indicators, but not tooth loss per se, with SCCHN risk.

PMID- 20049637
TI  - Mechanical evaluation of large-size fourth-generation composite femur and tibia
      models.
AB  - Composite analogue bone models provide consistent geometric and structural
      properties that represent a valuable asset in a range of biomechanical analyses
      and testing procedures. The objective of this study was to evaluate the
      diaphyseal structural properties of the large-size Fourth-Generation composite
      analogue femur and tibia models concentrated on mechanical behaviors under axial
      compression, bending and torsion. Thirty of each large-size composite analogue
      models (femora and tibiae) were tested under medial-lateral four-point bending,
      anterior-posterior four-point bending, axial compression and external rotational
      torque to evaluate flexural rigidity, axial stiffness, torsional rigidity and
      ultimate failure strength. The composite femur was tested under torsion at both
      the femoral neck and the mid-diaphyseal areas. Large-size Fourth-Generation
      composite replicate bones exhibited intra-specimen variations under 10% for all
      cases and was also found to perform within the biological range of healthy adult
      bones (age: <80 years old) range with respect to flexural rigidity (<8%) and
      torsional rigidity (<12%). The failure modes of these composite models were close
      to published findings for human bones (four-point bending: butterfly fragment
      fracture; torsional: spiral fracture; and compression: transverse fracture). The
      large-size composite analogue femur and tibia are close to ideal replicas for
      standardization in biomechanical analyses. One advantage of these analogue models
      is that their variability is significantly lower than that of cadaveric specimens
      for all loading regimens. Published results vary widely in cadaveric studies,
      which is likely due to the high anatomic variability among cadaveric specimens.
      This study evaluated and advanced our overall understanding of the capacity of
      composite analogue bone models mimic the structural properties of average healthy
      adult human bones.

PMID- 20049638
TI  - Incorporating histology into a 3D microscopic computer model of myocardium to
      study propagation at a cellular level.
AB  - We introduce a 3D model of cardiac tissue to study at a microscopic level the
      relationship between tissue morphology and propagation of depolarization. Unlike
      the classical bidomain approach, in which tissue properties are described by the
      apparent conductivity of the tissue, in this "microdomain" approach, we included
      histology by modeling the actual shape of the intracellular and extracellular
      spaces that contain spatially distributed gap-junctions and membranes. The
      histological model of the tissue was generated by a computer algorithm that can
      be tuned to model different histological changes. For healthy tissue, the model
      predicted a realistic conduction velocity of 0.42 m/s based solely on the
      parameters derived from histology. A comparison with a brick-shaped, simplified
      model showed that conduction depended to a moderate extent on the shape of
      myocytes; a comparison with a one-dimensional bidomain model with the same
      overall shape and structure showed that the apparent conductivity of the tissue
      can be used to create an equivalent bidomain model. In summary, the microdomain
      approach offers a means of directly incorporating structural and functional
      parameters into models of cardiac activation and propagation and thus provides a
      valuable bridge between the cellular and tissue domains in the myocardium.

PMID- 20049639
TI  - Towards using photo-plethysmogram amplitude to measure blood pressure during
      sleep.
AB  - There is considerable interest in non-intrusive and reliable continuous
      ambulatory blood pressure measurement systems. Pulse amplitude is the peak to
      trough amplitude of the photo-plethysmogram signal. We compared pulse amplitude
      with a currently popular parameter, the pulse arrival time (PAT), for estimating
      continuous systolic blood pressure (SBP). Overnight sleep data from 18 young,
      healthy subjects (14 M 4 F, age 24+/-5 years, BMI 23.8+/-4.0 kg/m2) was analyzed.
      We found that pulse amplitude was more effective than PAT for estimating SBP
      during sleep. Mean coherence between pulse amplitude and SBP was significantly
      stronger than that for PAT [p<0.001, 95% CI: 0.21-0.25 (finger), 0.11-0.14
      (wrist)]. Correlation between pulse amplitude and SBP was significantly stronger
      than that for PAT [p<0.001, 95% CI: 0.46-0.53 (finger), 0.13-0.20 (wrist)]. SBP
      estimation errors were significantly lower using pulse amplitude [p<0.001, 95%
      CI: -1.55 to -1.29 mmHg (finger), -0.53 to -0.36 mmHg (wrist)]. We also found
      that while pulse amplitude was closely related to SBP, the relationship weakened
      during and around REM sleep (ANOVA of REM, transitional Wake-REM and transitional
      REM-Sleep versus other sleep states: F=24.7, p<0.001). These results suggest that
      pulse amplitude is potentially a more suitable measure than pulse arrival time
      for estimating continuous blood pressure.

PMID- 20049640
TI  - Micro-macro hybrid soft-lithography master (MMHSM) fabrication for lab-on-a-chip
      applications.
AB  - We present a novel micro-macro hybrid soft-lithography master (MMHSM) fabrication
      technique where microdevices having both microscale and macroscale features can
      be replicated with a single soft-lithography step. A poly(methyl methacrylate)
      (PMMA) master having macroscale structures was first created by a bench-top
      milling machine. An imprinting master mold having microscale structures was then
      imprinted on the PMMA surface through a hot-embossing process to obtain a PMMA
      master mold. A poly(dimethylsiloxane) (PDMS) master was then replicated from this
      PMMA master through a standard soft-lithography process. This process allowed
      both microscale (height: 3-20 microm, width: 20-500 microm) and macroscale
      (height: 3.5 mm, width: 1.2-7 mm) structures to co-exist on the PDMS master mold,
      from which final PDMS devices could be easily stamped out in large quantities.
      Microfluidic structures requiring macroscale dimensions in height, such as
      reservoirs or fluidic tubing interconnects, could be directly built into PDMS
      microfluidic devices without the typically used manual punching process. This
      significantly reduced alignment errors and time required for such manual
      fabrication steps. In this paper, we successfully demonstrated the utility of
      this novel hybrid fabrication method by fabricating a PDMS microfluidic device
      with 40 built-in fluidic interfaces and a PDMS multi-compartment neuron co
      culture platform, where millimeter-scale compartments are connected via arrays of
      20 microm wide and 200 microm long microfluidic channels. The resulting
      structures were characterized for the integrity of the transferred pattern sizes
      and the surface roughness using scanning electron microscopy and optical
      profilometry.

PMID- 20049641
TI  - p53 as a marker of prognosis in African-American women with breast cancer.
AB  - BACKGROUND: p53 overexpression has been identified as a poor prognostic marker in
      breast cancer. We investigate the value of p53 status within the context of stage
      and intrinsic subtype classification (subtype), in a group of African-American
      (AA) women of lower socioeconomic status (SES) with primary breast cancer.
      METHODS: Participants were 331 consecutive AA women treated at an urban hospital
      (median follow-up 41 months) with known subtype [luminal A = estrogen receptor
      (ER)+ and/or progesterone receptor (PR)+, human epidermal growth factor receptor
      2 (HER2)-; luminal B = ER+ and/or PR+, HER2+; HER2+ = ER-, PR-, HER2+; basal = ER
      , PR-, HER2-, cytokeratin (CK)5/6+, and/or HER1+; and unclassified = negative for
      all five markers] and p53 (Pab1801 antibody) immunohistochemical status.
      Proportional hazards regression models were used to select and evaluate factors
      prognostic for all-cause mortality. RESULTS: p53+ status was associated with
      grade 3 tumors, ER/PR- status, and basal subtype. On univariate analysis, factors
      related to survival were stage, grade [(3/1) hazard ratio (HR) = 2.64; 95%
      confidence interval (CI), 1.15-6.07], subtype [(ex. basal/luminal A) HR = 2.15;
      95% CI, 1.34-3.45], and p53 status [(+/-) HR = 1.77; 95% CI, 1.15-2.72].
      Multivariable modeling indicated that p53+ status remained a negative prognostic
      factor (HR = 1.63; 95% CI, 1.01-2.59) after adjustment for effects of age, stage,
      grade, and subtype; 5-year adjusted survival was significantly greater for p53-
      (66.7%) than p53+ cases (54.7%). CONCLUSION: p53 status is an independent
      predictor of survival after consideration of other strong prognostic factors such
      as stage, tumor grade, and subtype, and thus may be useful in identifying AA
      women at high risk of breast cancer mortality.

PMID- 20049643
TI  - Ancient Greek and Greco-Roman methods in modern surgical treatment of cancer.

PMID- 20049642
TI  - Difference between proximal and distal microsatellite-unstable sporadic
      colorectal cancers: analysis of clinicopathological and molecular features and
      prognoses.
AB  - BACKGROUND: Distal microsatellite instability (MSI)-high colorectal cancers
      (CRCs) have been investigated by few studies and are generally regarded as having
      similar features to proximal MSI-high CRCs. In the present study, we aimed to
      elucidate whether distal sporadic MSI-high CRCs displayed distinguished
      clinicopathological and molecular features from proximal MSI-high CRCs. METHODS:
      All patients who underwent their first surgical resections for stage I-IV
      sporadic CRCs between August 2003 and August 2006 were initially considered for
      enrollment, and their MSI data were prospectively collected. Among them, 135
      patients with MSI-high CRCs (86 proximal and 49 distal CRCs) were finally
      identified. The clinicopathological and molecular characteristics, and prognosis
      of these cases with MSI-high CRCs were reviewed and compared according to tumor
      site (proximal versus distal). RESULTS: Distal MSI-high CRCs showed significantly
      more frequent association with younger age, male gender, differentiated
      histology, small tumor size, distant metastasis, stability in BAT25 and BAT26,
      and hMLH1 expression on immunohistochemical staining as compared with proximal
      MSI-high CRCs. In addition, distal MSI-high CRCs demonstrated significantly worse
      3-year overall and disease-free survival rates than proximal MSI-high CRCs (87.0%
      versus 97.4%; 81.6% versus 95.9%). For stage III-IV CRCs, distal MSI-high CRCs
      also showed significantly worse 3-year overall and disease-free survival rates
      than proximal MSI-high CRCs (72.2% vs. 90.5%; 58.3% vs. 94.4%). CONCLUSIONS:
      These results indicated that distal sporadic MSI-high CRCs formed a distinct
      subgroup with distinguished clinicopathological and molecular features from
      proximal MSI-high CRCs. In addition, this study demonstrated that distal MSI-high
      CRCs had worse prognosis than proximal MSI-high CRCs.

PMID- 20049644
TI  - KRAS and BRAF mutational status in primary colorectal tumors and related
      metastatic sites: biological and clinical implications.
AB  - BACKGROUND: KRAS and BRAF mutations in primary colorectal tumors (PT) are
      predictive of nonresponse to anti-epidermal growth factor receptor (EGFR)
      antibodies in patients with metastatic colorectal cancer (mCRC). The question of
      primary resistance to anti-EGFR treatment as a result of the presence of KRAS or
      BRAF mutations only in metastases has been raised but not resolved. METHODS: We
      analyzed the mutational status of KRAS and BRAF in 64 new patients with mCRC and
      performed a systematic review of published data from 285 patients. RESULTS: A
      total of 285 and 95 matched PT/metastases were available for the analysis of the
      KRAS and the BRAF status, respectively. An identical mutational pattern of KRAS
      in PT and the matching metastases were reported in all the cases but 14 (5%). In
      six cases (2%), KRAS was mutated in the PT and wild type in the metastatic site,
      whereas in eight cases (3%), KRAS was wild type in the PT and mutated in the
      metastatic site. An identical mutational pattern of BRAF in PT and the matching
      metastases was reported in all but two cases (3%). In one case (1.5%), BRAF was
      mutated in the PT and wild type in the metastatic site, whereas in one case
      (1.5%), BRAF was wild type in the PT and mutated in the metastatic site.
      CONCLUSIONS: The acquisition by metastases of a KRAS or a BRAF mutation that was
      not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is
      not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.

PMID- 20049645
TI  - Revisiting the natural history of tuberculosis. The inclusion of constant
      reinfection, host tolerance, and damage-response frameworks leads to a better
      understanding of latent infection and its evolution towards active disease.
AB  - Once Mycobacterium tuberculosis infects a person it can persist for a long time
      in a process called latent tuberculosis infection (LTBI). LTBI has traditionally
      been considered to involve the bacilli remaining in a non-replicating state
      (dormant) in old lesions but still retaining their ability to induce reactivation
      and cause active tuberculosis (TB) once a disruption of the immune response takes
      place. The present review aims to challenge these concepts by including recent
      experimental data supporting LTBI as a constant endogenous reinfection process as
      well as the recently introduced concepts of damage-response and tolerance
      frameworks to explain TB induction. These frameworks highlight the key role of an
      exaggerated and intolerant host response against M. tuberculosis bacilli which
      induces the classical TB cavity in immunocompetent adults once the constant
      endogenous reinfection process has resulted in the presence of bacilli in the
      upper lobes, where they can grow faster and the immune response is delayed. This
      essay intends to provide new clues to understanding the induction of TB in non
      immunosuppressed patients.

PMID- 20049646
TI  - The role of heparanase in diseases of the glomeruli.
AB  - The glomerular basement membrane (GBM) is a kind of net that remains in a state
      of dynamic equilibrium. Heparan sulfate proteoglycans (HSPGs) are among its most
      important components. There are much data indicating the significance of these
      proteoglycans in protecting proteins such as albumins from penetrating to the
      urine, although some new data indicate that loss of proteoglycans does not always
      lead to proteinuria. Heparanase is an enzyme which cleaves beta 1,4 D: 
      glucuronic bonds in sugar groups of HSPGs. Thus it is supposed that heparanase
      may have an important role in the pathogenesis of proteinuria. Increased
      heparanase expression and activity in the course of many glomerular diseases was
      observed. The most widely documented is the significance of heparanase in the
      pathogenesis of diabetic nephropathy. Moreover, heparanase acts as a signaling
      molecule and may influence the concentrations of active growth factors in the
      GBM. It is being investigated whether heparanase inhibition may cause decreased
      proteinuria. The heparanase inhibitor PI-88 (phosphomannopentaose sulfate) was
      effective as an antiproteinuric drug in an experimental model of membranous
      nephropathy. Nevertheless, this drug is burdened by some toxicity, so further
      investigations should be considered.

PMID- 20049647
TI  - Role of SLAM-associated protein in the pathogenesis of autoimmune diseases and
      immunological disorders.
AB  - Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is an
      adaptor molecule containing a Src homology 2 (SH2) domain. SAP is expressed in T
      cells and natural killer (NK) cells and binds to the cytoplasmic domains of SLAM
      family receptors, resulting in the subsequent recruitment of Fyn. The SAP
      (SH2D1A) gene is located on the X chromosome and is responsible for X-linked
      lymphoproliferative disease, characterized by higher susceptibility to Epstein
      Barr virus infection. The SAP-mediated signal is not only essential for the
      development of NKT cells, i.e. unconventional CD1d-restricted T cells with
      invariant Valpha14 T cell receptors, but also for the regulation of the function
      of NK cells and conventional T cells. The role of SAP-mediated signaling in the
      induction of autoimmune diseases has been analyzed using animal models such as
      lupus, hepatitis, and graft-versus-host disease and is considered important in
      their pathogenesis in humans. In this review we highlight the current findings on
      SAP-mediated signaling in hematopoietic cells and discuss its importance in
      autoimmune diseases and immunological disorders.

PMID- 20049648
TI  - Immunotherapy of rheumatoid arthritis targeting inflammatory cytokines and
      autoreactive T cells.
AB  - Rheumatoid arthritis is a chronic disorder for which there is no known cure.
      Concentrating on specific elements of the abnormal immune response that
      characterizes the disease, scientists are reaching into biotechnology's bag of
      tricks to develop immunotherapeutic techniques. This paper will present some
      advances in the immunotherapy of rheumatoid arthritis targeting inflammatory
      cytokines and autoreactive T cells.

PMID- 20049649
TI  - Cathelicidin LL-37: a multitask antimicrobial peptide.
AB  - The antimicrobial peptide LL-37 is the only known member of the cathelicidin
      family of peptides expressed in humans. LL-37 is a multifunctional host defense
      molecule essential for normal immune responses to infection and tissue injury. LL
      37 peptide is a potent killer of different microorganisms with the ability to
      prevent immunostimulatory effects of bacterial wall molecules such as
      lipopolysaccharide and can therefore protect against lethal endotoxemia.
      Additional reported activities of LL-37 include chemoattractant function,
      inhibition of neutrophil apoptosis, and stimulation of angiogenesis, tissue
      regeneration, and cytokine release (e.g. IL-8). Cellular production of LL-37 is
      affected by multiple factors, including bacterial products, host cytokines,
      availability of oxygen, and sun exposure through the activation of CAP-18 gene
      expression by vitamin D(3). At infection sites, the function of LL-37 can be
      inhibited by charge-driven interactions with DNA and F-actin released from dead
      neutrophils and other cells lysed as the result of inflammation. A better
      understanding of LL-37's biological properties is necessary for its possible
      therapeutic application for immunomodulatory purposes as well as in treating
      bacterial infection.

PMID- 20049650
TI  - The enzymatic activity of type 1 iodothyronine deiodinase (D1) is low in liver
      hemangioma: a preliminary study.
AB  - Type 1 iodothyronine deiodinase (D1) is a crucial enzyme which converts the
      prohormone thyroxine (T4) into active tri-iodothyronine (T3). There has been
      strong evidence that the metabolism of thyroid hormones is disturbed in some
      neoplastic tissues such as thyroid, renal, and breast cancer. However, there are
      few available data about D1 enzyme activity in benign tumors such as hemangioma,
      which is the most common primary liver tumor. Hence this study aimed to determine
      the enzymatic activity of D1 in hemangiomas in relation to healthy liver tissue.
      Seven tumors and healthy control tissues were obtained from patients who had
      liver resection due to hemangioma. The activity was assessed by measurement of
      radioactive iodine released by deiodination catalyzed by D1. It was found that D1
      activity was significantly lower in the hemangiomas than in the healthy
      surrounding tissue (p = 0.0017). The results indicated that thyroid hormones play
      important roles not only in the regulation of cell metabolism, but also in cell
      growth, division, and apoptosis. The active form T3 acts through its nuclear
      receptors and influences the up- and down-regulation of target genes. Healthy
      liver tissue expresses a high level of D1, but disturbed D1 activity may result
      in changes in the local concentration of T3 which may impair gene transcription.
      These finding demonstrate a low enzymatic activity of D1 in liver hemangioma and
      suggest an as yet unknown role of thyroid hormones in this type of benign liver
      tumor.

PMID- 20049651
TI  - Serodiagnostic efficacy of Mycobacterium tuberculosis 30/32-kDa mycolyl
      transferase complex, ESAT-6, and CFP-10 in patients with active tuberculosis.
AB  - Elimination of tuberculosis (TB) largely depends upon definitive rapid diagnosis
      and treatment. Widely used diagnostic tests do not qualify for use in a
      developing country due to lack of either desired accuracy or their cost. In the
      present study an enzyme-linked immunosorbent assay was used to evaluate the
      diagnostic potential of an immuno-dominant 30/32-kDa mycolyl transferase complex
      (Ag85 complex) and Mycobacterium tuberculosis-specific proteins (ESAT-6 and CFP
      10) of the RD1 region. Higher sensitivity (84.1%) with Ag85 complex was observed
      compared with ESAT-6 (64.9%) and CFP-10 (66%), with almost similar specificity
      (Ag85: 85.2%, ESAT-6: 88.9%, CFP-10: 85.2%), whereas the individual components of
      Ag85 complex, i.e. Ag85A, Ag85B, and Ag85C, showed sensitivities of 44.6, 34, and
      80.9% and specificities of 55.6, 74.1, and 40.7% respectively. A cocktail of Ag85
      complex, ESAT-6, CFP-10, Ag85A, Ag85B, and Ag85C antigens also could not help in
      increasing either sensitivity (51.1%) or specificity (85.2%). Furthermore,
      immunoblot analysis using clinical isolates as well as a standard strain (H37Rv)
      of M. tuberculosis also showed strong reactivity of sera from TB patients to Ag85
      complex and, to a lesser extent, also to ESAT-6. To conclude, use of Ag85 complex
      along with ESAT-6 and CFP-10 seems to be promising in minimizing the
      heterogeneous sero-responses of adult TB cases.

PMID- 20049652
TI  - Initial experience with laparoscopic crural closure in the management of hiatal
      hernia in obese patients undergoing sleeve gastrectomy.
AB  - BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) and/or
      hiatal hernia (HH) is significantly increased in morbidly obese patients.
      Laparoscopic bariatric procedures such as gastric banding (LGB) and Roux-en-Y
      gastric bypass have been shown to improve both obesity and reflux symptoms. The
      aim of this paper is to evaluate the effectiveness of laparoscopic sleeve
      gastrectomy (LSG) and hiatal hernia repair (HHR) for the treatment of obesity
      complicated by HH. METHODS: From October 2008, six patients underwent HHR in
      addition to LSG. Clinical outcomes have been evaluated in terms of GERD symptoms
      improvement or resolution, interruption of antireflux medication, and X-ray
      evidence of HH recurrence. RESULTS: Symptomatic HH was diagnosed preoperatively
      in four patients. In two additional patients, HH was asymptomatic and it was
      diagnosed intraoperatively. Prosthetic reinforcement of crural closure was
      performed in two symptomatic cases with a HH >5 cm. Mortality was nil and no
      complications occurred. After a mean follow-up of 4 months, GERD symptoms
      resolution occurred in three patients, while the other patient reported an
      improvement of reflux. Body mass index had fallen from 43.4 to 36.2 kg/m(2). A
      small recurrence in the patient with persistence of reflux symptoms has been
      radiologically reported. CONCLUSIONS: Laparoscopic crural closure in addition to
      LSG could represent a valuable option for the synchronous management of morbid
      obesity and HH, providing good outcomes in terms of weight loss and GERD symptoms
      control.

PMID- 20049653
TI  - Morbidly obese patients--who undergoes bariatric surgery?
AB  - BACKGROUND: Bariatric surgery particularly benefits patients with obesity-related
      comorbidities such as type 2 diabetes and obstructive sleep apnea. We aimed to
      examine whether the variables that influence treatment choice differ between
      morbidly obese patients undergoing bariatric surgery and those opting for
      conservative treatments. METHODS: A total of 505 consecutive morbidly obese
      patients (72% women; mean (SD) age 42 (12) years) who attended our tertiary care
      center between December 2005 and February 2007 were examined by a
      multidisciplinary team and offered surgical or conservative treatment. The chi
      square test, independent samples t test, and multiple logistic regression were
      used in the statistical analyses. RESULTS: A total of 249 (49%) patients
      underwent bariatric surgery. When compared to the conservative group of patients,
      the surgery group was characterized by a significantly higher mean (SD) BMI
      (46.5(6.2) vs. 43.2(5.5) kg/m(2), p < 0.001), earlier onset of obesity (40% vs.
      26% before 12 years of age, p < 0.001), and lower age (41(11) vs. 44(13) years, p
      = 0.002). In contrast, the groups did not differ significantly with respect to
      gender or obesity-related comorbidities. After adjustments for gender, age, onset
      of obesity, and the number of comorbidities, multiple regression revealed that
      patients with BMI 40-50 or >50 kg/m(2) had between 3 (OR = 3.0; 95% CI 1.9-4.9, p
      < 0.001) and 6 (OR = 5.7; 95% CI 3.0-11.0, p < 0.001) times the chance of
      undergoing bariatric surgery when compared to patients with a BMI <40 kg/m(2)
      (reference). CONCLUSION: Our data indicates that increasing BMI rather than
      obesity-related comorbidities, predicted treatment choice in morbidly obese
      patients.

PMID- 20049654
TI  - Long-term outcomes of laparoscopic Roux-en-Y gastric bypass in US veterans.
AB  - BACKGROUND: The objective of this study is to evaluate the long-term outcomes
      following laparoscopic Roux-en-Y gastric bypass (LREYGB) in veteran patients. The
      VA bariatric population differs from its counterpart in the private sector by the
      predominance of a male population, a higher percentage of patients from a lower
      socioeconomic background, a higher mean age, and a higher rate of obesity-related
      comorbidities. METHODS: A retrospective review with prospectively collected data
      was used to analyze postoperative changes of comorbidities and percent of excess
      weight loss (% EWL) in consecutive patients who underwent LREYGB between August
      2003 and September 2006. RESULTS: Among 70 patients, 73% were men with a mean age
      of 52 years (29-66 years). Average preoperative weight and body mass index were
      310 lbs (224-397 lbs) and 46 kg/m(2) (36-60 kg/m(2)), respectively. The incidence
      of major and minor complications was 1.4% and 15.7%, respectively. There were no
      mortalities. Follow-up (f/u) was possible in all patients. At a mean f/u rate of
      39 months, % EWL was 56%. At 1, 3, and 5 years, % EWL was 61%, 53%, and 59%,
      respectively. Thirty-five patients (50%) had type 2 diabetes mellitus (T2DM).
      Glycosylated hemoglobin concentrations returned to normal levels in 91% of
      patients and improved in an additional 6% of T2DM cases. Only 7% of patients are
      still maintained on antidiabetic medications. In patients with more than 1 year
      f/u, most other comorbidities were improved or resolved. CONCLUSIONS: Long-term
      f/u of LREYGB in veteran patients demonstrated significant and durable weight
      loss (56% EWL) with marked improvements in comorbidities especially T2DM.

PMID- 20049656
TI  - Studies on plasmalogen-selective phospholipase A2 in brain.
AB  - Plasmalogen-selective phospholipase A(2) (PlsEtn-PLA(2)) has been purified from
      pig brain using multiple column chromatographic procedure. The purified enzyme
      migrates as a single band on polyacrylamide. It is stimulated by Triton X-100 and
      inhibited by sodium deoxycholate. Purified PlsEtn-PLA(2) is inhibited by
      iodoacetate, and this inhibition can be prevented by beta-meracaptoethanol.
      Treatment of neuronal cell cultures with kainic acid stimulates PlsEtn-PLA(2)
      activity in a dose-dependent manner, and this stimulation can be blocked by
      Ly294486, a selective kainic acid receptor antagonist. Activities of PlsEtn
      PLA(2) are markedly increased in plasma membrane and synaptosomal plasma membrane
      fraction prepared from nucleus basalis and hippocampal region of brains from
      Alzheimer disease patients compared to age-matched controls. It is proposed that
      accumulation of ceramide and increased expression of cytokines may be responsible
      for the stimulation of PlsEtn-PLA(2) in Alzheimer disease.

PMID- 20049655
TI  - Spine remodeling and synaptic modification.
AB  - The majority of excitatory communication occurs at dendritic spines, and spine
      modifications accompany synaptic modifications under both physiological and
      pathological conditions. Although it is increasingly clear that spine remodeling
      is required for synaptic modification, the exact functions and underlying
      molecular mechanisms remain unclear. Here, we review recent progress on this
      topic and discuss the functions of spine remodeling in a broad sense to include
      both alterations in spine size and actin dynamics. We propose that these two
      aspects of actin remodeling have distinct contributions to synaptic modification.

PMID- 20049657
TI  - An fMRI study of multimodal semantic and phonological processing in reading
      disabled adolescents.
AB  - Using functional magnetic resonance imaging, we investigated multimodal (visual
      and auditory) semantic and unimodal (visual only) phonological processing in
      reading disabled (RD) adolescents and non-impaired (NI) control participants. We
      found reduced activation for RD relative to NI in a number of left-hemisphere
      reading-related areas across all processing tasks regardless of task type
      (semantic vs. phonological) or modality (auditory vs. visual modality). Moreover,
      activation differences in these regions, which included the inferior frontal
      gyrus, the superior temporal gyrus, and the occipitotemporal region, were largely
      independent of in-scanner performance in our auditory semantic task. That is,
      although RD participants and NI participants differed in performance in visually
      presented conditions, they did not differ significantly in the auditory
      condition, yet similar patterns of reduced activation were observed in these
      regions across conditions. These findings indicate a neurobiological marker in RD
      that is independent of task, modality, or performance. These findings are
      discussed in the context of current neurobiological models of RD.

PMID- 20049658
TI  - Sun protection intervention for highway workers: long-term efficacy of UV
      photography and skin cancer information on men's protective cognitions and
      behavior.
AB  - BACKGROUND: The risk for skin cancer is increased among older males and outdoor
      workers who have high levels of ultraviolet (UV) exposure. PURPOSE: This study
      was designed to examine the long-term efficacy of UV photography interventions on
      male outdoor workers, the potential mediators of its impact, and the efficacy of
      UV photography and skin cancer vs. aging information with this population.
      METHODS: One hundred forty-eight male outdoor workers were randomly assigned to
      one of four intervention conditions or a control condition in a two by two plus
      one factorial design. The men in the intervention conditions received or did not
      receive a UV photo of their face and watched either a photoaging or skin cancer
      educational video. Participants completed pre-intervention, immediate post
      intervention, and 2-month and 1-year follow-up assessments. RESULTS: Analysis of
      covariance and structural equation modeling revealed that participants in the UV
      photography and cancer information interventions reported higher levels of sun
      protection cognitions, which were significant partial mediators of increases in
      sun protection behaviors and decreases in skin color. CONCLUSIONS: This study
      provides evidence for effective sun protection interventions on male outdoor
      workers that may help reduce skin cancer risk.

PMID- 20049659
TI  - Examining the individual and perceived neighborhood associations of leisure-time
      physical activity in persons with spinal cord injury.
AB  - BACKGROUND: Theory of Planned Behavior (TPB) constructs have been shown to be
      useful for explaining leisure-time physical activity (LTPA) in persons with
      spinal cord injury (SCI). However, other factors not captured by the TPB may also
      be important predictors of LTPA for this population. PURPOSE: The purpose of this
      study is to examine the role of neighborhood perceptions within the context of
      the TPB for understanding LTPA in persons living with SCI. METHODS: This is a
      cross-sectional analysis (n = 574) using structural equation modeling involving
      measures of the TPB constructs, perceived neighborhood esthetics and sidewalks,
      and LTPA. RESULTS: TPB constructs explained 57% of the variance in intentions and
      12% of the variance in behavior. Inclusion of the neighborhood variables to the
      model resulted in an additional 1% of the variance explained in intentions, with
      esthetics exhibiting significant positive relationships with the TPB variables.
      CONCLUSION: Integrating perceived neighborhood esthetics into the TPB framework
      provides additional understanding of LTPA intentions in persons living with SCI.

PMID- 20049660
TI  - Worry as a moderator of the association between risk perceptions and quitting
      intentions in young adult and adult smokers.
AB  - BACKGROUND: Although much work addresses the association between risk perceptions
      and behavior, much less attention has been devoted to identifying psychosocial
      and sociodemographic moderators of this relationship. PURPOSE: We explored
      whether worry moderates the relationship between risk perceptions and behavioral
      intentions in an adult sample (where the relationship is typically positive) and
      a young adult sample (where we have found that the relationship can be negative).
      METHOD: Two samples of smokers (adults and college students) were asked to report
      worry, risk perceptions, and quitting intentions as part of two cessation
      interventions. RESULTS: Among low-worry individuals, the risk
      perception/intentions relationship was positive in the adult sample and negative
      in the young adult sample. However, among high-worry individuals, the
      relationship was negative in the adult sample (and nonsignificant in the young
      adult sample). CONCLUSIONS: These findings suggest that worry can moderate the
      extent to which risk perceptions motivate risk-related intentions and that the
      nature of such moderation may depend on other factors such as age.

PMID- 20049661
TI  - Education and smoking: confounding or effect modification by phenotypic
      personality traits?
AB  - BACKGROUND: Little is known about whether educational gradients in smoking
      patterns can be explained by financial measures of socioeconomic status (SES)
      and/or personality traits. PURPOSE: To assess whether the relationship of
      education to (1) never smoking and (2) having quit smoking would be confounded by
      financial measures of SES or by personality; whether lower Neuroticism and higher
      Conscientiousness would be associated with having abstained from or quit smoking;
      and whether education effects were modified by personality. METHOD: Using data
      from the Midlife Development in the US National Survey, 2,429 individuals were
      classified as current (n = 695), former (n = 999), or never (n = 735) smokers.
      Multinomial logistic regressions examined study questions. RESULTS: Greater
      education was strongly associated with both never and former smoking, with no
      confounding by financial status and personality. Never smoking was associated
      with lower Openness and higher Conscientiousness, while have quit was associated
      with higher Neuroticism. Education interacted additively with Conscientiousness
      to increase and with Openness to decrease the probability of never smoking.
      CONCLUSIONS: Education and personality should be considered unconfounded smoking
      risks in epidemiologic and clinical studies. Educational associations with
      smoking may vary by personality dispositions, and prevention and intervention
      programs should consider both sets of factors.

PMID- 20049662
TI  - [Study of pathogenic mediators in diabetic macular edema by analysis of the
      vitreous humour. Role of erythropoietin and somatostatin].

PMID- 20049663
TI  - [Macular focal treatment guided by the retinal thickness map of the HD-OCT Cirrus
      versus fluorescein angiography for retinal vein occlusions].

PMID- 20049664
TI  - [Retrobulbar triamcinolone injection and glycemic control].
AB  - OBJECTIVE: To look for alterations of glycemic control as a secondary systemic
      effect of the retrobulbar injection of triamcinolone acetonide in diabetic and
      non-diabetic patients. MATERIALS AND METHODS: We studied 40 patients (25 men and
      15 women, 20 with and 20 without diabetes). The injection site in all patients
      was the retrobulbar space, with one injection of 1ml triamcinolone acetonide (40
      mg). Capillary blood glucose was measured at 8 a.m. on the day of treatment as
      baseline, and on the 7 days following the injection. RESULTS: The mean capillary
      blood glucose level was significantly higher at the day 1 post-treatment visit
      (218.3 +/- 70 mg/dl) than at baseline (138.3 +/- 21 mg/dl) in the diabetic group
      (p< 0.001). On day 4 post-treatment, capillary blood glucose remained
      significantly elevated compared to baseline in the diabetic patients (185.7 +/-
      67.8 mg/dl) (p= 0.01). Mean capillary blood glucose was significantly higher at
      the day 1 post-treatment visit (154.2 +/- 30.1 mg/dl) than at baseline (119.3 +/-
      12 mg/dl) in the non-diabetic group (p< 0.001). At the day 4 post-treatment
      visit, capillary blood glucose remained significantly elevated compared to
      baseline in the non-diabetic patients (145.5 +/- 55.8 mg/dl) (p= 0.01).
      CONCLUSIONS: The administration of triamcinolone acetonide by retrobulbar
      injection was followed by elevations in capillary glycemia in diabetic and non
      diabetic patients, but severe hyperglycemia was observed only in the diabetic
      group.

PMID- 20049665
TI  - [Morphological macular changes after cataract surgery: risk factors].
AB  - OBJECTIVE: To analyze morphological macular changes after uncomplicated cataract
      surgery and their correlation with age and arterial hypertension. METHODS: Total
      macular volume (TMV), foveal volume (FOVOL) and foveal thickness (FOV) in
      patients who had undergone cataract surgery were measured using OCT3 Stratus
      before surgery, the day after the intervention and one month later. The data were
      analyzed using SPSS 15.0 software. RESULTS: The study group was composed of 114
      eyes from 114 patients. The mean TMV, FOVOL and FOV in the subgroup of patients
      with signal strength over 6 before cataract surgery were 6.59 (SD0.67) microm(3);
      0.16 (SD0.02) microm(3) and 204.97 (SD29.79) microm. One month after surgery the
      measurements were TMV: 6.93 (SD0.56) microm(3); FOVOL: 0.17 (SD0.06) microm(3)
      and FOV: 218.07 (SD87.60) microm. We found statistically significant differences
      (P<0.05) in TMV, but not in FOVOL or FOV. The group of patients under 74 years
      showed a greater increase in TMV. Patients with arterial hypertension did not
      show an increase in TMV or FOV compared to patients without arterial
      hypertension. CONCLUSIONS: We found a sub-morphological macular oedema one month
      after uncomplicated cataract surgery, with age being a risk factor for developing
      a greater increase in TMV. Arterial hypertension does not seem to be a risk
      factor for these changes.

PMID- 20049666
TI  - [Relationship between standard automated perimetry and optic nerve head
      topography performed with the Heidelberg Retina Tomograph].
AB  - PURPOSE: To determine the correlations between optic nerve head (ONH) parameters
      measured with the Heidelberg Retina Tomograph (HRT), and the main outcomes of
      standard automated perimetry (SAP) in normal, ocular hypertensive, glaucoma
      suspects and glaucomatous subjects. METHODS: Four hundred and twenty-three
      patients were enrolled in the study and classified into four groups depending on
      baseline intraocular pressure, optic nerve head morphology, and SAP results: 87
      normal eyes, 192 ocular hypertensive eyes, 70 glaucoma suspects and 74
      glaucomatous eyes. In the different diagnostic groups, Pearson's correlation
      coefficients were calculated between ONH parameters and mean deviation, pattern
      standard deviation (PSD), number of altered points in each quadrant of the visual
      field (superior-nasal, inferior-nasal, superior-temporal and inferior-temporal),
      number of points altered at different probability levels, and threshold values at
      each point of SAP. RESULTS: In the normal and ocular hypertensive groups, only a
      few weak correlations were found between HRT and SAP parameters. The strength and
      number of significant correlations increased in the suspected glaucoma group. The
      glaucoma group had the strongest correlations, particularly between cup/disc
      ratio and rim/disc ratio with MD (r=0.479) and between rim area and PSD
      (r=0.444). CONCLUSIONS: Weak to moderate correlations were found between some ONH
      parameters obtained with the HRT and SAP results in the glaucoma group.

PMID- 20049667
TI  - [Peripheral vitreoretinal traction exploration by Staurenghi 230 lens and HRA
      II].
AB  - PURPOSE: To report a new technique to explore peripheral vitreous-retinal
      tractions in patients with acute posterior vitreous detachment. MATERIAL AND
      METHODS: A population of 65 patients with acute posterior vitreous detachment was
      studied by panfunduscopic SLO 230 lens and HRA-II to detect peripheral retinal
      tears and vitreous-retinal tractions. RESULTS: In our study, using indirect
      ophthalmoscopic exploration, we identified eleven patients with at least one
      retinal tear. HRA-II combined with the Staurenghi SLO 230 lens was capable of
      detecting 100% of these lesions. In addition, by means of this technology, we
      identified dark retinal zones that corresponded to peripheral retinal traction in
      six patients. None of the 65 patients complained of pain or photophobia during
      the exploration with this contact lens. Retinal tears and peripheral vitreous
      retinal traction were treated by argon laser photocoagulation to create a firm
      chorioretinal adhesion. In two patients we found new retinal tears in the follow
      up, with these new lesions detected by indirect ophthalmoscopy and HRA-II with
      SLO 230 lens. CONCLUSION: HRA-II with the panfunduscopic Staurenghi SLO 230 lens
      can complement the exploration of patients with acute posterior vitreous
      detachment and can help to detect tractional zones that could develop into
      retinal tears.

PMID- 20049668
TI  - [Unilateral exophthalmos as the debut of a non-secretory multiple myeloma].
AB  - CASE REPORT: A 56 year-old male presented blurred vision and diplopia for 2
      months, left unilateral exophthalmos, restricted ocular motility and papilledema.
      The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth
      rib and fourth dorsal vertebral body with associated masses of soft tissues.
      Biopsy was performed and the diagnosis of plasma cell neoplasm was established.
      The diagnosis of non-secretory multiple myeloma was made by analytical criteria
      and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed.
      CONCLUSIONS: The ophthalmologist can play an important role in the diagnosis of
      systemic neoplasms that require the intervention of a multidisciplinary team.

PMID- 20049669
TI  - [Successful Boston keratoprosthesis in a patient with Lyell's syndrome].
AB  - CASE REPORT: We present the case of a woman readmitted to our service to receive
      treatment for severe ophthalmic manifestations due to Lyell's syndrome. This
      intense affectation of the ocular surface along with limbal stem cell deficiency
      are grounds for treatment with Boston type 1 keratoprosthesis, which provided a
      stable and very satisfactory functional result. DISCUSSION: As noted in this case
      report, the Boston Type 1 keratoprosthesis seems to be a viable option after
      multiple failed corneal grafts or in situations with a poor prognosis for primary
      penetrating keratoplasty because of limbal stem cell deficiency, such as Lyell's
      syndrome.

PMID- 20049670
TI  - [An ophthalmology surgeon in the 18th Century: Victoria de Felix].

PMID- 20049671
TI  - [Georges Louis Leclerc, Count of Buffon - Montbard, 1707 - Paris, 1788].

PMID- 20049673
TI  - Comorbidities in primary aldosteronism.
AB  - Patients presenting with primary aldosteronism experience more cardiovascular
      events than patients with essential hypertension independent of blood pressure.
      Therefore, the presence of primary aldosteronism should be detected, not only to
      determine the cause of hypertension, but also to prevent such complications. This
      review focuses on human data regarding increased end-organ damage and
      comorbidities in primary aldosteronism. Special emphasis is put on the effects of
      aldosterone excess on blood vessels, the heart, the kidney, and the brain. The
      data reviewed in our article demonstrate that primary aldosteronism is associated
      with a prevalence of cerebro-, cardiovascular and renal complications that are
      out of proportion to the blood pressure and benefits substantially from treatment
      in the long term. In this view, adrenalectomy and aldosterone antagonist
      treatment seem to be of considerable therapeutic value to control and limit the
      progression of comorbidities in primary aldosteronism.

PMID- 20049672
TI  - Hypothalamic and plasmatic angiotensin metabolism in L-NAME treated rats.
AB  - In order to study the interaction between the renin-angiotensin system (RAS) and
      nitric oxide (NO), we analyzed the activity of aspartyl- (AspAP), glutamyl-
      (GluAP), alanyl- (AlaAP), and cystinylaminopeptidase (CysAP) enzymes involved in
      the RAS cascade, in the hypothalamus, and plasma of normotensive adult male rats
      after the inhibition of NO production with the NO synthase inhibitor L-NAME (L-N
      (G)-nitroarginine methyl ester). L-NAME treatment produced a significant increase
      of systolic blood pressure (SBP). In plasma, while GluAP activity decreased
      significantly, suggesting a lower Ang III formation, the other aminopeptidases
      did not change after L-NAME treatment. In hypothalamus, the activities of AspAP
      and CysAP were not affected after L-NAME treatment. In contrast, GluAP and AlaAP
      increased significantly. These results suggested mainly a higher formation of Ang
      III, but also higher levels of Ang IV in the hypothalamus of L-NAME treated rats.
      Both peptides have hypertensive properties at central level. On the contrary, Ang
      III may counteract the hypertensive action of Ang II at the periphery. Therefore,
      the increased SBP in L-NAME treated rats may be due in part to the increased
      activity of GluAP and AlaAP in hypothalamus and to a decreased activity of GluAP
      in plasma.

PMID- 20049674
TI  - TASK1 and TASK3 potassium channels: determinants of aldosterone secretion and
      adrenocortical zonation.
AB  - Potassium channels control the membrane voltage of aldosterone-producing zona
      glomerulosa cells. They are responsible for the unique K(+) sensitivity of these
      cells and are important molecular targets of angiotensin II signaling. Among the
      78 pore-forming K(+) channels in human genome only a few are found in adrenal
      glands. The 2-P-domain K(+) channels TASK1 and TASK3 are strongly expressed in
      the adrenal cortex and produce a background K(+) conductance, which is pivotal
      for the regulation of the aldosterone secretion in zona glomerulosa cells.
      Disruption of the TASK1 gene in mice resulted in an autonomous aldosterone
      production and caused a remarkable aberrant expression of aldosterone synthase in
      zona fasciculata cells that normally produce glucocorticoids. After puberty, only
      in male mice aldosterone production was switched off in the zona fasciculata and
      regular zonation of aldosterone synthase occurred. In double mutant TASK1(-/
      )/TASK3(-/-) mice, also adult male mice displayed primary hyperaldosteronism.
      Therefore, these knockout mice are interesting models to study mechanisms of
      autonomous aldosterone production and adrenocortical zonation. These data suggest
      that modifications of the adrenocortical K(+) conductances could also contribute
      to autonomic aldosterone production and primary hyperaldosteronism in humans.

PMID- 20049675
TI  - Estradiol supplementation helps overcome central leptin resistance of
      ovariectomized mice on a high fat diet.
AB  - Ovariectomized mice on a high fat diet represent a model of diet-induced obesity
      during estrogen deficiency. Here, we tested the hypothesis that sensitivity to
      centrally administered leptin in ovariectomized mice with diet-induced obesity
      could be restored by estrogen supplementation. Ovariectomized C57BL/6 female mice
      were fed either a standard or high fat diet until they were 27 weeks old.
      Ovariectomized mice on a high fat diet developed extreme obesity and
      hyperleptinemia and moderate hyperinsulinemia compared to those on a standard
      diet. For the last 4 weeks, 17beta-estradiol-3-benzoate or its vehicle was
      administered subcutaneously in a 4-day cyclic regimen. Finally, leptin or saline
      was injected into the third ventricle, and food intake and body weight were
      measured for 36 h. In ovariectomized mice fed a standard diet, the decrease in
      food intake and body weight was significant and was pronounced in 17beta
      estradiol-3-benzoate-supplemented mice. The response to centrally injected leptin
      in ovariectomized mice on a high fat diet was insignificant, whereas in 17beta
      estradiol-3-benzoate-supplemented mice, the effect was significant, particularly
      with respect to body weight. We showed for the first time that central
      insensitivity to leptin in ovariectomized diet-induced obese mice was restored
      with 17beta-estradiol-3-benzoate supplementation, which also attenuated most of
      the parameters of metabolic syndrome. Only circulating adiponectin, a peripheral
      insulin sensitivity marker, was lowered following 17beta-estradiol-3-benzoate
      administration in both high fat and standard diet-fed ovariectomized mice,
      despite of decreased or unchanged glycemia, respectively.

PMID- 20049676
TI  - [Methodical requirements for quality reports of nursing facilities].
AB  - BACKGROUND: Since 2009 there is a legal obligation in Germany to provide quality
      reports for all nursing facilities. OBJECTIVE AND METHODS: Criteria for measuring
      and presenting the quality of care defined for health services are applied to the
      area of nursing care. The German Nursing-Transparency-Order for nursing homes has
      been compared with those attributes. RESULTS: Prior to realisation of the concept
      of publishing quality reports of care facilities, the definition of high-quality
      care standards, an explicit objective for quality reporting and the definition of
      addressees are required. The quality indicators to be derived must be relevant
      from the user's point of view as well as from professional perspectives. Benefits
      and undesirable effects must be weighted out mutually. Relevant for the choice of
      quality indicators are the methodical attributes: strength of evidence, precision
      of definitions, ability of discrimination, reliability and validity. To make the
      results comparable between facilities, it is suggested to include an equally
      stratified random sampling of persons. An aggregation or summation of the results
      may basically only occur when the results have a common content coherence
      (correlation) and the same importance (weighting). Through explicit
      specifications for the assessment, for example, so-called knock-out criteria, it
      must be assured that in essential events like damages under non-expert care,
      there are no compensations by other results. The German Nursing-Transparency
      Order for nursing homes fulfils only one part of the generally established
      methodical quality criteria. CONCLUSION: The procedure for the choice of quality
      indicators must be made clear; the methodical quality must be tested and the test
      results must be published. Above all it must be proven with test results that the
      appraisal of experts and users agrees with the results of the nursing
      transparency (validity). An accompanying research is absolutely necessary.

PMID- 20049677
TI  - [Test-retest reliability of the OVIS Questionnaire--an instrument to evaluate
      oncological care from a patient's point of view].
AB  - OBJECTIVES: The OVIS study aims to outline and assess the health-care situation
      of patients with breast, prostate and skin cancer in Schleswig-Holstein. The used
      form contains questions regarding diagnosis, therapy, rehabilitation, post
      operative health care, and quality of life and was administered approximately one
      year after primary therapy. The objective of this study (substudy of the OVIS
      study) is the evaluation of the test-retest reliability of this questionnaire in
      patients with breast cancer, who were questioned during and one year after
      primary therapy. METHODS: The study population was recruited during their
      ambulant chemotherapy and includes women with adjuvant and neoadjuvant treatment
      of their breast cancer. Patients with advanced metastasis were excluded. In total
      56 patients, for whom medical records and both questionnaires were available,
      were included in this analysis. The test-retest reliability was measured using
      rates of absolute agreement and Cohen's kappa with a 95% confidence interval.
      RESULTS: Of the 73 closed questions, 41% showed good and 52% showed moderate test
      retest reliability. Test-retest reliability was high for questions regarding
      important moments (e.g., notification of breast cancer diagnosis), diagnostic
      (e.g., mammography) or therapeutic procedures (e.g., ablation mammae).
      CONCLUSIONS: Although the time span between both questionings was one year, the
      acquired values of the test-retest reliability are consistent with those from
      comparable studies with shorter questioning intervals. The used questionnaire is
      a reliable instrument to determine the health care situation of women with breast
      cancer in Schleswig-Holstein.

PMID- 20049678
TI  - [Harmless: fact or fiction?].
AB  - The aim of this article is to critically discuss what conclusions can be drawn
      about health risks or innocuousness of exposures from an epistemiological point
      of view. For the interpretation of the epidemiological evidence of health risks,
      several assumptions have to be met--some of them cannot be empirically checked.
      Replication of study findings does not necessarily imply causation. However, it
      is possible to falsify hypotheses based on emipirical studies. This falsification
      principle can also be used for the interpretation of a single study. If we are
      able to falsify all non-causal hypotheses, the causal hypothesis is the only
      hypothesis that has survived and therefore should be taken seriously. Regardless
      of the number and kind of empirical studies, we cannot logically prove that an
      exposure has a harmful effect or not. Therefore, a hypothesis that could not be
      falsified until now should be used for political or other decisions even if there
      is a chance that this hypothesis will be falsified in the future when based on
      more appropriate trials of falsification.

PMID- 20049679
TI  - [Early recognition centres for patients at risk of developing schizophrenia in
      Germany].
AB  - AIM OF THE STUDY: This survey gives a review over the development of early
      diagnosis and treatment of patients being at risk of developing psychoses in
      Germany. METHODS: A survey was carried out at 34 psychiatric departments at
      university hospitals in Germany from January until June 2008. RESULTS: So far, 12
      early detection centres have been set up in Germany offering outpatient
      diagnostic and intervention services. CONCLUSIONS: Early recognition and
      intervention of psychoses has greatly improved in Germany in the last ten years.
      Therefore more research is imperative.

PMID- 20049680
TI  - [Cancer survival analysis in Germany--heading towards representative and
      comparable findings].
AB  - Cancer is an important issue within the German health care system with an
      estimated annual number of 435 000 incident cases and almost 210 000 deaths. Data
      of population-based cancer registries enable us to identify improvements of
      survival in oncological patients due to progress in therapeutic care and
      secondary prevention, as well as to investigate regional and international
      differences of this outcome. Comparing cancer survival rates, however, requires
      considering the impact of both methodical approaches and data quality. Potential
      factors of influence like algorithms, reference population, completeness of case
      ascertainment and quality of follow-up are discussed. For the first time
      harmonized proceedings are recommended in order to achieve comparability of
      population-based cancer survival rates in Germany.

PMID- 20049681
TI  - [Telephone case management: is it beneficial for the care of depression patients
      in Germany? A systematic literature survey].
AB  - BACKGROUND: Strategies are needed to effectively improve the management of
      depression in Germany. Can telephone case management (TCM) be a promising
      strategy to improve depression care in the German health-care system? METHODS: A
      systematic literature review in PubMed, Cochrane Library, ISI Web of Science,
      PsycINFO and PSYNEXplus for randomised controlled trials (RCT) that evaluate TCM
      was carried out. RESULTS: Ten RCTs that compared TCM to treatment as usual were
      found. TCM was more effective in reducing depressive symptoms and in increasing
      satisfaction with care than treatment as usual. Whether TCM was capable of
      significantly improving pharmacotherapy compliance remained controversial.
      DISCUSSION: The effectiveness of TCM seemed to be related to the health-care
      system structure in which it was implemented. Most studies on TCM were conducted
      in US-American Health Maintenance Organizations. Thus, it is unclear to what
      extent these results can be transferred to the German health system. However, in
      the light of the promising results of these studies it seems to be worthwhile to
      test TCM also under conditions of the German health-care system.

PMID- 20049682
TI  - [Mutual communication is often lacking--interviews with professional care givers
      on ambulatory palliative care].
AB  - GOAL OF THE STUDY: Within the study "possibilities and borders of ambulatory
      palliative care" interviews with employees of the outpatient care service were
      carried out. Thereby the subjective view of the professional care givers was the
      maintaining of interest. The focus was on problems in palliative home care, co
      operation with other professionals and family caregivers as well as the
      conditions of their work. METHODS: With the help of qualitative manual
      interviews, the questioning took place with nine cooperating ambulatory care
      services. The interviews were recorded, transliterated, analysed and evaluated
      following the qualitative content analysis of Mayring. RESULTS: From the ambulant
      caregivers' point of view the causes for a failure of home care are particularly
      the poor cooperation with other professionals and the large distress of the
      family caregivers. In contrast, they estimate that a good cooperation with the
      family doctor and other participants of the care, a sufficient qualification and
      networking as well as committed family caregivers and pleased patients are
      beneficial factors for ambulatory palliative care. CONCLUSION: An efficient
      implementation of specialised ambulatory care models (SAPV) is imperative in
      order to ensure an interdisciplinary and cooperative care for palliative patients
      and to afford an effective working field for professional care givers.

PMID- 20049683
TI  - [Health screening and vaccination status--results from a patient survey in German
      general practices].
AB  - The vaccination status of German adults needs improvement. Low participation is
      also known in health screening programmes like the "Check up 35" which is offered
      every two years for adults aged 35 or above. However, the number of participants
      in health screening increases with age whereas vaccination status decreases.
      Within a study about patients' attitudes towards prevention in primary care, we
      investigated the knowledge about the vaccination status. Therefore, an anonymous
      survey was conducted among 333 patients from five general practices in 2007. 76%
      of the potential participants in health screening declared that they utilise it
      at least infrequently. In contrast to those who participate frequently in health
      screening (67%), those who participate infrequently (38%) or never (33%) but
      declare that their vaccination status is complete are significantly rare. Due to
      the results of our study it has to be discussed whether the health screening
      "Check up 35" should be regularly accompanied with vaccination counselling.

PMID- 20049685
TI  - [Health economic evaluation of the integrated care project "OPTI-MuM"].
AB  - AIM: The objective of this study is to evaluate the economic performance of a
      population-based integrated care project in comparison to standard care. METHODS:
      The perspective adopted is that of the participating statutory health insurance
      companies. The well-defined target region allows the distinction of participants
      and non-participants. The quasi-experimental study design, which is based on
      routine data of the participating health insurers, is able to reduce the bias
      caused by the non-randomised group assignment. Based on the year of enrollment
      two separate cohorts were generated. RESULTS: The comparison of group differences
      before and after a propensity score matching shows that this method provides
      appropriate control groups for both cohorts of participants. Taking into account
      4,840 of the 5,164 participants, total savings of ? 87,252 were calculated.
      CONCLUSION: These findings suggest that the method of propensity score matching
      permits a scientifically sound performance measurement for population-based care
      contracts.

PMID- 20049684
TI  - [Pain and pain management for children in Greifswald and East Pomerania:
      comparison with the results of the German Health Interview and Examination Survey
      for Children and Adolescents (KiGGS)].
AB  - AIM OF THE STUDY: Pain in children and adolescents in Germany is a common health
      problem which has a high socioeconomic impact. There have been no studies
      allowing a reliable estimation of the prevalence of pain in children in the 5
      (th) grade (age range 9-13 years) in schools in the region of the city of
      Greifswald and the administrative district East Pomerania. This population-based
      cross-sectional study examined the prevalence of pain in children, the treatment
      of pain and compared these data with the results of the German Health Interview
      and Examination Survey for Children and Adolescents (KiGGS). METHODS: Data were
      collected within the extended dental school examination in autumn 2007 including
      a self-completion questionnaire for the students. Also the parents answered a
      self-completion questionnaire containing questions on their children's socio
      economic status. The pain and sociodemographic questions are compatible with
      those used in the "German Health Survey for Children and Adolescents" (KiGGS).
      RESULTS: Students from 19 schools completed a questionnaire on general pain
      (n=852, proportion of response: 93.2%, mean age: 10 years). Comparing to the
      KiGGS the overall 3-month prevalence is much higher (95.5%). For boys and girls
      headache is the pain associated with the most burden ("Hauptschmerz"). 1/4 of the
      girls (27.9%) and 1/5 (22.4%) of the boys reported their pain with the most
      burden during the last 3 months with a frequency of at least one time per week.
      Students with low socio-economic status took medication against pain
      ("Hauptschmerz") less frequently than students with high socio-economic status.
      Because of their pain ("Hauptschmerz") students with low socio-economic status
      visited a doctor less often than students with a mean or high socio-economic
      status. CONCLUSION: Compared to other epidemiological studies, pain is also a
      common health problem for children in the city of Greifswald and the
      administrative district East Pomerania. The data base enables comprehensive
      conclusions on the health-related state of students in Greifswald/East Pomerania.
      Further studies should examine additional factors on medication and the degree of
      doctor?s visits, e. g., parental attitudes towards medication and parental
      motivation towards the degree of visiting a doctor.

PMID- 20049686
TI  - ["Responsiveness" in psychiatric outpatient care and in hostel management].
AB  - OBJECTIVE: Responsiveness is a concept developed by the World Health Organisation
      (WHO) to evaluate health system performance. It measures how well a health system
      meets its users' legitimate expectations in non-medical related service aspects.
      Responsiveness consists of the categories "patient orientation" and "respect for
      persons". It is operationalised by nine (8+1) domains. This project aims to
      explore the responsiveness concept as a possibility to evaluate the performance
      of mental health care. METHOD: Face to face interviews with users of outpatient
      and hostel mental health services by means of a standardised instrument,
      developed by WHO were carried out. RESULTS: Overall responsiveness in outpatient
      care was rated by a lower proportion of users negative than responsiveness in
      hostel care (15 vs. 20%). Socio-demographic characteristics were related only to
      responsiveness ratings in hostel care when legal guardianship was considered.
      Domains indicated as most important (attention, participation) in out-patient
      care did not perform well there. In hostel care the domains attention and respect
      were rated as most important. These domains performed well. DISCUSSION AND
      CONCLUSIONS: The results are in line with the literature and adequately reflect
      the realities in mental health care. The responsiveness concept offers a
      systematic approach for considering the categories "patient orientation" and
      "respect for persons" as quality criteria in mental health care. Evaluating
      mental health service provision using the concept of responsiveness, indicates
      where to launch reforms in health care.

PMID- 20049687
TI  - [Psychooncological care for breast cancer patients in hospitals and in the
      outpatient sector].
AB  - BACKGROUND: Psycho-oncological care is nowadays an integral part of patient
      oriented health care in oncology. Psycho-oncological services are considered in
      the formulation of guidelines and the existence of such services is a
      precondition for the certification of organ centres. METHODS: For a status quo
      analysis of psycho-oncological health-care services for breast cancer patients in
      inpatient and outpatient care, 101 hospitals (inpatient care) and 124 health-care
      professionals in outpatient psycho-oncological services were questioned by mail.
      RESULTS: Psycho-oncological care in the hospital setting is mainly carried out by
      psychologists and physicians. 2-100% (median: 32.5%) of breast cancer patients
      receive psycho-oncological treatment. The proportion of psycho-oncological
      treatment performed by psychologists is higher in bigger hospitals and in
      hospitals which are part of a breast centre. In outpatient care, psycho
      oncological treatment is mainly carried out by psychologists. Most of the
      interventions are individual therapy sessions (group therapy: median 20%). Most
      of the participants in the outpatient sector are psychodynamic (43%) or
      behavioural (23%) therapists, 40% report other therapeutic backgrounds.
      CONCLUSION: Both the inpatient and the outpatient sectors show a high
      heterogeneity in psycho-oncological care. The results for the inpatient setting
      indicate increasing professionalisation and orientation towards certification
      criteria and treatment guidelines. The heterogeneity in outpatient psycho
      oncological care can be interpreted as desirable diversity which allows for the
      consideration of the varying needs of patients with different diagnoses, disease
      stages, and treatments.

PMID- 20049688
TI  - [UV risk perception by the general public: results of a representative
      questionnaire in Germany].
AB  - AIM OF THE STUDY: For public health promotion purposes it is important to know
      how the general public perceives the risk factor "UV exposure" and how UV risk
      perception is connected to health-related attitudes and beliefs. The aim of the
      study was to collect representative data about UV risk perception in Germany.
      METHODS: A representative telephone survey using the ADM design was carried out
      among 1 501 German residents between May and July 2007. Variables related to UV
      risk knowledge, relevance of risk topics in every-day thinking and risk estimates
      were investigated. Data regarding a subjective benefit evaluation of UV
      exposition was also collected. RESULTS: The results suggest no essential gaps in
      the general knowledge about UV risks, except for the underestimation of UV
      related cataracts. The respondents thought it extremely likely that UV exposure
      would cause health damage such as skin cancer, photoaging or sun burns. People
      were asked to report how often they had thought about a number of health risks
      including UV risks in the last two weeks. It was established that UV risks are
      present but not dominant in people's every-day thinking. Along with it, the risk
      evaluation proves to be rather moderate. The mean value for respondents'
      perceived personal risk is M=5.1, in the midsection of the given 10-point scale.
      The results show that perceived personal risk is not influenced by the serious UV
      health risks such as cancer or cataracts. The results also indicate that UV
      benefit and UV risk perception are not strongly related to one another.
      CONCLUSIONS: In summary, participants' perception and assessment of the various
      health risks of UV exposure seem to be realistic, but the UV risk assessment it
      is not related to the perception of personal risk. One must therefore assume that
      UV health risk information and education campaigns do not necessarily lead to a
      change in the perception of personal UV risk. Rather than addressing primarily
      risk knowledge, UV risk communication should focus more on motivational aspects
      and consider the role of UV benefit perception.

PMID- 20049689
TI  - Isolation of amniotic epithelial stem cells.
AB  - Many of the cell types that can be isolated from placental tissues retain
      phenotypic plasticity that makes them an interesting source of cells for
      regenerative medicine. Several procedures for the isolation of stem cells from
      different parts of the placenta have been reported. This unit describes a
      detailed and simple protocol for the selective isolation of amniotic epithelial
      cells from human term placenta without disturbing the mesenchymal layer. We also
      introduce a simple density separation technique for the enrichment of the
      population for SSEA-4 positive cells.

PMID- 20049690
TI  - In situ hybridization to identify gut stem cells.
AB  - In recent years, considerable effort has been directed towards identifying the
      repertoire of genes specifically expressed in adult stem cells. In this unit, we
      describe an in situ hybridization protocol adapted for the analysis of gene
      expression in the intestinal mucosa. This methodology allows researchers to
      quickly visualize the expression profile of putative stem cell markers with a
      high degree of sensitivity and resolution.

PMID- 20049691
TI  - Regioisomer characterization of triacylglycerols by non-aqueous reversed-phase
      liquid chromatography/electrospray ionization mass spectrometry using silver
      nitrate as a postcolumn reagent.
AB  - Triacylglycerols (TAGs) provide a challenge for mass spectrometry (MS) analysis
      because of their complexity. In particular, for dietary, nutritional and
      metabolic purposes, the positional placement of fatty acids on the glycerol
      backbone of TAGs is a crucial aspect. To solve this problem, we have investigated
      the TAGs' fragmentation patterns using an ion trap mass spectrometer. A series of
      pure regioisomeric pairs of TAGs (POP/PPO, POO/OPO and OSO/SOO) were cationized
      by Ag(+) after their separation by non-aqueous reversed-phase liquid
      chromatography (NARP-LC) before MS to improve MS sensitivity. Electrospray
      ionization-MS (ESI-MS) conditions were optimized in order to produce
      characteristic [M + Ag + AgNO(3)](+) ions from each TAG, which were then
      fragmented to produce MS/MS spectra and then fragmented further to produce up to
      MS(5) spectra. The observation of ions produced by LC-MS(5) of on-line Ag(+)
      cationized TAG provided unambiguous information on the fatty acid distribution on
      the glycerol backbone. These strategies of MS to MS(5) experiments were applied
      to identify components and to determine the regiospecificity of TAG within a
      complex mixture of lipids in natural oils.

PMID- 20049692
TI  - Decomposition of 1,1-dimethyl-1-silacyclobutane on a tungsten filament--evidence
      of both ring C-C and ring Si-C bond cleavages.
AB  - The decomposition of 1,1-dimethyl-1-silacyclobutane (DMSCB) on a heated tungsten
      filament has been studied using vacuum ultraviolet laser single photon ionization
      time-of-flight mass spectrometry. It is found that the decomposition of DMSCB on
      the W filament to form ethene and 1,1-dimethylsilene is a catalytic process. In
      addition, two other decomposition channels exist to produce methyl radicals via
      the Si-CH(3) bond cleavage and to form propene (or
      cyclopropane)/dimethylsilylene. It has been demonstrated that both the formation
      of ethene and that of propene are stepwise processes initiated by the cleavage of
      a ring C-C bond and a ring Si-C bond, respectively, to form diradical
      intermediates, followed by the breaking of the remaining central bonds in the
      diradicals. The formation of ethene via an initial cleavage of a ring C-C bond is
      dominant over that of propene via an initial cleavage of a ring Si-C bond. When
      the collision-free condition is voided, secondary reactions in the gas-phase
      produce various methyl-substituted 1,3-disilacyclobutane molecules. The dominant
      of all is found to be 1,1,3,3-tetramethyl-1,3-disilacyclobutane originated from
      the dimerization of 1,1-dimethylsilene.

PMID- 20049693
TI  - Hybrid pooled-unpooled design for cost-efficient measurement of biomarkers.
AB  - Evaluating biomarkers in epidemiological studies can be expensive and time
      consuming. Many investigators use techniques such as random sampling or pooling
      biospecimens in order to cut costs and save time on experiments. Commonly,
      analyses based on pooled data are strongly restricted by distributional
      assumptions that are challenging to validate because of the pooled biospecimens.
      Random sampling provides data that can be easily analyzed. However, random
      sampling methods are not optimal cost-efficient designs for estimating means. We
      propose and examine a cost-efficient hybrid design that involves taking a sample
      of both pooled and unpooled data in an optimal proportion in order to efficiently
      estimate the unknown parameters of the biomarker distribution. In addition, we
      find that this design can be used to estimate and account for different types of
      measurement and pooling error, without the need to collect validation data or
      repeated measurements. We show an example where application of the hybrid design
      leads to minimization of a given loss function based on variances of the
      estimators of the unknown parameters. Monte Carlo simulation and biomarker data
      from a study on coronary heart disease are used to demonstrate the proposed
      methodology.

PMID- 20049694
TI  - Welcome to EMBO Molecular Medicine!

PMID- 20049695
TI  - EMBO Molecular Medicine--where molecular biology meets clinical research.

PMID- 20049696
TI  - From concepts to cures--and back.

PMID- 20049697
TI  - EMBO Molecular Medicine: Conquering new frontiers.

PMID- 20049698
TI  - More than the sum of its parts: new mouse models for dissecting the genetic
      complexities of Williams-Beuren syndrome.
AB  - Psychiatric disorders are a common, severe and disabling group of diseases where
      progress in finding novel molecular targets has been slow. This is partly due to
      our lack of understanding of the molecular pathophysiology of these conditions as
      they play out in the brain (Insel & Scolnick, 2006). Since many of these diseases
      (such as schizophrenia, bipolar disorder or autism) are highly heritable, a
      genetic approach to dissecting the risk architecture is a promising avenue for
      molecular medicine; however, variants in single genes frequently present in the
      population have only small to moderate effects on complex behavioural phenotypes
      (O'Donovan et al, 2008).

PMID- 20049699
TI  - "Filoviruses": a real pandemic threat?
AB  - Filoviruses are zoonotic and among the deadliest viruses known to mankind, with
      mortality rates in outbreaks reaching up to 90%. Despite numerous efforts to
      identify the host reservoir(s), the transmission cycle of filoviruses between the
      animal host(s) and humans remains unclear. The last decade has witnessed an
      increase in filovirus outbreaks with a changing epidemiology. The high mortality
      rates and lack of effective antiviral drugs or preventive vaccines has propagated
      the fear that filoviruses may become a real pandemic threat. This article
      discusses the factors that could influence the possible pandemic potential of
      filoviruses and elaborates on the prerequisites for the containment of future
      outbreaks, which would help prevent the evolution of filovirus into more virulent
      and more transmissible viruses.

PMID- 20049701
TI  - Expression of the alternative oxidase complements cytochrome c oxidase deficiency
      in human cells.
AB  - Cytochrome c oxidase (COX) deficiency is associated with a wide spectrum of
      clinical conditions, ranging from early onset devastating encephalomyopathy and
      cardiomyopathy, to neurological diseases in adulthood and in the elderly. No
      method of compensating successfully for COX deficiency has been reported so far.
      In vitro, COX-deficient human cells require additional glucose, pyruvate and
      uridine for normal growth and are specifically sensitive to oxidative stress.
      Here, we have tested whether the expression of a mitochondrially targeted,
      cyanide-resistant, alternative oxidase (AOX) from Ciona intestinalis could
      alleviate the metabolic abnormalities of COX-deficient human cells either from a
      patient harbouring a COX15 pathological mutation or rendered deficient by
      silencing the COX10 gene using shRNA. We demonstrate that the expression of the
      AOX, well-tolerated by the cells, compensates for both the growth defect and the
      pronounced oxidant-sensitivity of COX-deficient human cells.

PMID- 20049700
TI  - Spotlight on Mycobacteria and dendritic cells: will novel targets to fight
      tuberculosis emerge?
AB  - Over thousands of years microbes and mammals have co-evolved, resulting in
      extraordinarily sophisticated molecular mechanisms permitting the organisms to
      survive together. Mycobacterium tuberculosis is one of the best examples of
      successful co-evolution, since the bacilli have infected one third of the human
      population, but in 90% of the cases without causing overt disease. Despite this,
      increasing incidence of Human Immunodeficiency Virus (HIV) infection and the
      emergence of drug-resistant strains means that tuberculosis is in fact an
      extremely serious emerging threat to global health. Decades of work have focused
      on the interaction of this pathogen with its established cellular host, the
      macrophage, but still novel therapeautics remain elusive. While the macrophage is
      clearly important, recent evidence suggests that understanding the role of
      dendritic cells, which are key regulators of immunity, may be a crucial step in
      identifying new means of controlling this disease. Novel technologies, in
      particular genome-wide transcriptome analyses, are advancing our ability to
      dissect the complex dynamic relationships between dendritic cells and
      mycobacteria, highlighting new areas for study that have not been previously
      explored.

PMID- 20049702
TI  - The antibiotic ADEP reprogrammes ClpP, switching it from a regulated to an
      uncontrolled protease.
AB  - A novel class of antibiotic acyldepsipeptides (designated ADEPs) exerts its
      unique antibacterial activity by targeting the peptidase caseinolytic protease P
      (ClpP). ClpP forms proteolytic complexes with heat shock proteins (Hsp100) that
      select and process substrate proteins for ClpP-mediated degradation. Here, we
      analyse the molecular mechanism of ADEP action and demonstrate that ADEPs
      abrogate ClpP interaction with cooperating Hsp100 adenosine triphosphatases
      (ATPases). Consequently, ADEP treated bacteria are affected in ClpP-dependent
      general and regulatory proteolysis. At the same time, ADEPs also activate ClpP by
      converting it from a tightly regulated peptidase, which can only degrade short
      peptides, into a proteolytic machinery that recognizes and degrades unfolded
      polypeptides. In vivo nascent polypeptide chains represent the putative primary
      target of ADEP-activated ClpP, providing a rationale for the antibacterial
      activity of the ADEPs. Thus, ADEPs cause a complete functional reprogramming of
      the Clp-protease complex.

PMID- 20049703
TI  - Induced chromosome deletions cause hypersociability and other features of
      Williams-Beuren syndrome in mice.
AB  - The neurodevelopmental disorder Williams-Beuren syndrome is caused by spontaneous
      approximately 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23.
      To functionally dissect the deletion and identify dosage-sensitive genes, we
      created two half-deletions of the conserved syntenic region on mouse chromosome
      5G2. Proximal deletion (PD) mice lack Gtf2i to Limk1, distal deletion (DD) mice
      lack Limk1 to Fkbp6, and the double heterozygotes (D/P) model the complete human
      deletion. Gene transcript levels in brain are generally consistent with gene
      dosage. Increased sociability and acoustic startle response are associated with
      PD, and cognitive defects with DD. Both PD and D/P males are growth-retarded,
      while skulls are shortened and brains are smaller in DD and D/P. Lateral
      ventricle (LV) volumes are reduced, and neuronal cell density in the
      somatosensory cortex is increased, in PD and D/P. Motor skills are most impaired
      in D/P. Together, these partial deletion mice replicate crucial aspects of the
      human disorder and serve to identify genes and gene networks contributing to the
      neural substrates of complex behaviours and behavioural disorders.

PMID- 20049704
TI  - Oxygen-independent degradation of HIF-alpha via bioengineered VHL tumour
      suppressor complex.
AB  - Tumour hypoxia promotes the accumulation of the otherwise oxygen-labile hypoxia
      inducible factor (HIF)-alpha subunit whose expression is associated with cancer
      progression, poor prognosis and resistance to conventional radiation and
      chemotherapy. The oxygen-dependent degradation of HIF-alpha is carried out by the
      von Hippel-Lindau (VHL) protein-containing E3 that directly binds and
      ubiquitylates HIF-alpha for subsequent proteasomal destruction. Thus, the
      cellular proteins involved in the VHL-HIF pathway have been recognized as
      attractive molecular targets for cancer therapy. However, the various compounds
      designed to inhibit HIF-alpha or HIF-downstream targets, although promising, have
      shown limited success in the clinic. In the present study, we describe the
      bioengineering of VHL protein that removes the oxygen constraint in the
      recognition of HIF-alpha while preserving its E3 enzymatic activity. Using
      speckle variance-optical coherence tomography (sv-OCT), we demonstrate the
      dramatic inhibition of angiogenesis and growth regression of human renal cell
      carcinoma xenografts upon adenovirus-mediated delivery of the bioengineered VHL
      protein in a dorsal skin-fold window chamber model. These findings introduce the
      concept and feasibility of 'bio-tailored' enzymes in the treatment of HIF
      overexpressing tumours.

PMID- 20049705
TI  - Challenges in translational research.

PMID- 20049706
TI  - In a flurry of PINK, mitochondrial bioenergetics takes a leading role in
      Parkinson's disease.
AB  - For many years research in Parkinson's disease (PD) has linked mitochondrial
      dysfunction with the characteristic loss of dopaminergic neurons of the
      substantia nigra, accumulation of cytoplasmic inclusions termed Lewy bodies, and
      motor dysfunction (Henchcliffe & Beal, 2008). The most compelling connection is
      that Parkinsonism can be observed in both humans and animals following exposure
      to inhibitors of complex I of the electron transport chain (Betarbet et al,
      2002).

PMID- 20049707
TI  - Noise stresses the junctions to deaf.
AB  - Sitting in the rainforest in Costa Rica, you can hear rain, rushing water,
      howling monkeys, birds and crickets. All are in abundance and although they are
      tantalizing to all your senses, your sense of hearing picks up what you cannot
      see with your eyes or feel with your hands.

PMID- 20049708
TI  - Awaking stem cells from dormancy: growing old and fighting cancer.
AB  - It is generally accepted that a distinguishing property of stem cells (SCs), as
      compared to their more differentiated progenitors, is that of infrequent
      division, often referred to as 'quiescence'. As regards hematopoietic stem cells
      (HSC), their resistance to antiproliferative drugs supports this notion.
      Maintenance of quiescence is thought to be critical for the preservation of HSCs'
      function.

PMID- 20049709
TI  - Innate instruction of adaptive immunity revisited: the inflammasome.
AB  - The innate immune system regulates initial responses to pathogen invasion through
      a set of conserved pattern recognition receptors (PRR). The best-characterized
      PRRs are the Toll-like receptors, which regulate not only the initial pathogen
      defense response, but also adaptive immune responses. Thus, insight into the
      function of PRRs has major implications for our understanding of the physiology
      of vaccination and the pathophysiology of human disease. Recent advances in our
      understanding of a new class of pattern recognition receptors--NOD-like receptors
      (NLR)--have similarly provided insight into both innate and adaptive immunity. In
      particular, the NLR Nlrp3 (also known as Nalp3 or Cias1) forms an intracellular
      multimolecular complex with active caspase-1, called an inflammasome, creating a
      platform for regulating secretion of interleukin-1 (IL-1) family members. Given
      the important role of IL-1 in inflammatory diseases, from gout to rheumatoid
      arthritis, the importance of understanding the regulation of such a cytokine
      cannot be underestimated. In this review, we address new evidence supporting a
      role for adaptive immune activation by recently identified NLR agonists, with a
      particular focus on Nlrp3. Basic questions in our understanding of Nlrp3
      inflammasome activation are also presented.

PMID- 20049710
TI  - Parkinson's disease mutations in PINK1 result in decreased Complex I activity and
      deficient synaptic function.
AB  - Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced
      kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies
      on loss of function and overexpression implicate PINK1 in apoptosis, abnormal
      mitochondrial morphology, impaired dopamine release and motor deficits. However,
      the fundamental mechanism underlying these various phenotypes remains to be
      clarified. Using fruit fly and mouse models we show that PINK1 deficiency or
      clinical mutations impact on the function of Complex I of the mitochondrial
      respiratory chain, resulting in mitochondrial depolarization and increased
      sensitivity to apoptotic stress in mammalian cells and tissues. In Drosophila
      neurons, PINK1 deficiency affects synaptic function, as the reserve pool of
      synaptic vesicles is not mobilized during rapid stimulation. The fundamental
      importance of PINK1 for energy maintenance under increased demand is further
      corroborated as this deficit can be rescued by adding ATP to the synapse. The
      clinical relevance of our observations is demonstrated by the fact that human
      wild type PINK1, but not PINK1 containing clinical mutations, can rescue Complex
      1 deficiency. Our work suggests that Complex I deficiency underlies, at least
      partially, the pathogenesis of this hereditary form of PD. As Complex I
      dysfunction is also implicated in sporadic PD, a convergence of genetic and
      environmental causes of PD on a similar mitochondrial molecular mechanism appears
      to emerge.

PMID- 20049711
TI  - Neutralization of IFNgamma defeats haemophagocytosis in LCMV-infected perforin-
      and Rab27a-deficient mice.
AB  - Hereditary haemophagocytic lymphohistiocytosis (HLH) is a fatal inflammatory
      disease and treatments currently may lead to serious side effects. There is a
      pressing need for effective, less toxic treatments for this disease. Previous
      reports have suggested that interferon gamma (IFNgamma) has a role in the
      pathogenesis of HLH. Here, we report that blocking IFNgamma had a therapeutic
      effect in two different murine models of human hereditary HLH (perforin-deficient
      and Rab27a-deficient mice, both infected with lymphocytic choriomeningitis
      virus). Therapeutic administration of an anti-IFNgamma antibody induced recovery
      from haemophagocytosis in both genetic models, as evidenced by increased survival
      in perforin-deficient mice and correction of blood cytopenia, moderation of body
      temperature changes, decreased cytokinaemia, restoration of splenic architecture
      and reduced haemophagocytosis in the liver of both murine models. Involvement of
      the central nervous system in Rab27a-deficient mice was prevented by anti
      IFNgamma therapy. Hepatic T-cell infiltrates and virus persisted, with no
      detectable harm during the time course of these studies. These data strongly
      suggest that neutralization of IFNgamma could be used in humans to safely
      alleviate the clinical manifestations of haemophagocytosis.

PMID- 20049713
TI  - A meeting of minds: overcoming roadblocks in the development of therapies for
      neurodegenerative disorders.

PMID- 20049712
TI  - Vezatin, an integral membrane protein of adherens junctions, is required for the
      sound resilience of cochlear hair cells.
AB  - Loud sound exposure is a significant cause of hearing loss worldwide. We asked
      whether a lack of vezatin, an ubiquitous adherens junction protein, could result
      in noise-induced hearing loss. Conditional mutant mice bearing non-functional
      vezatin alleles only in the sensory cells of the inner ear (hair cells) indeed
      exhibited irreversible hearing loss after only one minute exposure to a 105 dB
      broadband sound. In addition, mutant mice spontaneously underwent late onset
      progressive hearing loss and vestibular dysfunction related to substantial hair
      cell death. We establish that vezatin is an integral membrane protein with two
      adjacent transmembrane domains, and cytoplasmic N- and C-terminal regions. Late
      recruitment of vezatin at junctions between MDCKII cells indicates that the
      protein does not play a role in the formation of junctions, but rather
      participates in their stability. Moreover, we show that vezatin directly
      interacts with radixin in its actin-binding conformation. Accordingly, we provide
      evidence that vezatin associates with actin filaments at cell-cell junctions. Our
      results emphasize the overlooked role of the junctions between hair cells and
      their supporting cells in the auditory epithelium resilience to sound trauma.

PMID- 20049714
TI  - RNAi-based therapeutics-current status, challenges and prospects.
AB  - RNA interference (RNAi) is a collection of small RNA directed mechanisms that
      result in sequence specific inhibition of gene expression. The notion that RNAi
      could lead to a new class of therapeutics caught the attention of many
      investigators soon after its discovery. The field of applied RNAi therapeutics
      has moved very quickly from lab to bedside. The RNAi approach has been widely
      used for drug development and several phase I and II clinical trials are under
      way. However, there are still some concerns and challenges to overcome for
      therapeutic applications. These include the potential for off-target effects,
      triggering innate immune responses and most importantly obtaining specific
      delivery into the cytoplasm of target cells. This review focuses on the current
      status of RNAi-based therapeutics, the challenges it faces and how to overcome
      them.

PMID- 20049715
TI  - PINK1 function in health and disease.
AB  - The role of mitochondria in sporadic Parkinson's disease (PD) has been debated
      for a little over 20 years since the description of complex I deficiency in the
      substantia nigra pars compacta (SNpc) of PD patients. However, the identification
      of recessive pathogenic mutations in the pink1 gene in familial PD cases firmly
      re-ignited interest in the pathophysiology of mitochondria in PD. PINK1 is a
      putative mitochondrial serine/threonine kinase, which protects cells against
      oxidative stress induced apoptosis. The mechanism by which this is achieved and
      the effect of the pathogenic mutations has been an area of intensive research
      over the past five years. Significant progress has been made and, in this review,
      we summarize the physiological roles that have been assigned to PINK1 and the
      potential mechanisms behind pathogenesis.

PMID- 20049716
TI  - Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and
      hyperinsulinism.
AB  - K(ATP) channels regulate insulin secretion from pancreatic beta-cells. Loss- and
      gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of
      this channel cause hyperinsulinism of infancy and neonatal diabetes,
      respectively. We report two novel mutations in the gating loop of Kir6.2 which
      cause neonatal diabetes with developmental delay (T293N) and hyperinsulinism
      (T294M). These mutations increase (T293N) or decrease (T294M) whole-cell K(ATP)
      currents, accounting for the different clinical phenotypes. The T293N mutation
      increases the intrinsic channel open probability (Po((0))), thereby indirectly
      decreasing channel inhibition by ATP and increasing whole-cell currents. T294M
      channels exhibit a dramatically reduced Po((0)) in the homozygous but not in the
      pseudo-heterozygous state. Unlike wild-type channels, hetT294M channels were
      activated by MgADP in the absence but not in the presence of MgATP; however, they
      are activated by MgGDP in both the absence and presence of MgGTP. These mutations
      demonstrate the importance of the gating loop of Kir channels in regulating
      Po((0)) and further suggest that Mg-nucleotide interaction with SUR1 may reduce
      ATP inhibition at Kir6.2.

PMID- 20049719
TI  - Framing a concept and an agenda for infectious diseases in EMBO Molecular
      Medicine.

PMID- 20049717
TI  - Heterochromatin protein 1alpha: a hallmark of cell proliferation relevant to
      clinical oncology.
AB  - Mammalian cells contain three closely related heterochromatin protein 1 (HP1)
      isoforms, HP1alpha, beta and gamma, which, by analogy to their unique counterpart
      in Schizosaccharomyces pombe, have been implicated in gene silencing, genome
      stability and chromosome segregation. However, the individual importance of each
      isoform during normal cell cycle and disease has remained an unresolved issue.
      Here, we reveal that HP1alpha shows a proliferation-dependent regulation, which
      neither HP1beta nor gamma display. During transient cell cycle exit, the HP1alpha
      mRNA and protein levels diminish. Transient depletion of HP1alpha, but not
      HP1beta or gamma, in tumoural and primary human cells leads to defects in
      chromosome segregation. Notably, analysis of an annotated collection of samples
      derived from carcinomas reveals an overexpression of HP1alpha mRNA and protein,
      which correlates with clinical data and disease outcome. Our results unveil a
      specific expression pattern for the HP1alpha isoform, suggesting a unique
      function related to cell division and tumour growth. The overexpression of
      HP1alpha constitutes a new example of a potential epigenetic contribution to
      tumourigenesis that is of clinical interest for cancer prognosis.

PMID- 20049720
TI  - A surrogate marker for Abeta42 production in the CNS.
AB  - Alzheimer's disease (AD) is the most common cause of dementia. There are
      currently no effective treatments that may delay the onset, slow the progression
      or prevent the disease. Unless such treatments are developed, the number of AD
      cases is expected to double in the next 30 years. There is overwhelming genetic
      and biochemical evidence that the aggregation and buildup of the amyloid-beta
      (Abeta) peptide plays a critical role in AD pathogenesis.

PMID- 20049721
TI  - Neurofibromatosis and lessons for the war on cancer.
AB  - In the war on cancer, a great deal of attention is being paid to knowing the
      'enemy'. It is widely believed that by understanding the driving forces
      underlying cancer, researchers can develop better ways to target the disease.
      Currently, large-scale efforts have been under taken to completely characterize
      molecular changes in common human cancers (http://cancergenome.nih.gov/) (Collins
      & Barker, 2007). However, as more is learned about cancer, the debate increases
      on what exactly the enemy is: cells making up the bulk of the tumour, rare tumour
      stem cells that can regrow the tumour, tumour microenvironment, the subset of
      cancer cells with metastatic potential, etc. Studies of the cancers associated
      with Neurofibromatosis type 1 (NF1) are helping to define the relationship
      between many of these different cell types. It is still unclear how these
      different enemies are related to each other and how they interact to wage
      cancer's war on the patient. 'If you know the enemy and know yourself you need
      not fear the results of a hundred battles.' - Sun Tzu, The Art of War, c. 500
      B.C.

PMID- 20049722
TI  - Jamming bacterial communication: new approaches for the treatment of infectious
      diseases.
AB  - The global rise of anti-microbial resistance, combined with the rapid rate of
      microbial evolution, and the slower development of novel antibiotics, underscores
      the urgent need for innovative therapeutics. We are facing a post-antibiotic era
      with a decreased armamentarium to combat infectious diseases. Development of
      novel drugs will rely on basic research aimed to increase our understanding of
      bacterial pathogenesis and the inter-cellular chemical signalling among bacterial
      cells. Such basic science, when combined with contemporary drug discovery
      technologies, may be translated into therapeutic applications to combat bacterial
      infections. In this review, we discuss many strategies aimed to interfere with
      bacterial cell-to-cell signalling via the quorum-sensing (QS) pathway to inhibit
      bacterial virulence and/or the development of microbial communities (known as
      biofilms), which are refractory to antibiotic treatment. QS antagonists should be
      viewed as blockers of pathogenicity rather than as anti-microbials and because QS
      is not involved in bacterial growth, inhibition of QS should not yield a strong
      selective pressure for development of resistance. QS inhibitors (QSIs) hold great
      expectations and we look forward to their application in fighting bacterial
      infections.

PMID- 20049723
TI  - Streptococcus pneumoniae evades human dendritic cell surveillance by pneumolysin
      expression.
AB  - Dendritic cells (DCs) protect the respiratory epithelium via induction of innate
      immune responses and priming of naive T cells during the initiation of adaptive
      immunity. Streptococcus pneumoniae, a commonly carried asymptomatic member of the
      human nasopharyngeal microflora, can cause invasive and inflammatory diseases and
      the cholesterol-dependent cytotoxin pneumolysin is a major pneumococcal virulence
      factor implicated in compounding tissue damage and mediating inflammatory
      responses. While most studies examining the impact of pneumolysin have been based
      on murine models, we have focused this study on human DC responses. We show that
      expression of haemolytic pneumolysin inhibits human DC maturation, induction of
      proinflammatory cytokines and activation of the inflammasome. Furthermore,
      intracellular production of pneumolysin induces caspase-dependent apoptosis in
      infected DCs. Similarly, clinical isolates with non-haemolytic pneumolysin were
      more proinflammatory and caused less apoptosis compared to clonally related
      strains with active pneumolysin. This study describes a novel role of pneumolysin
      in the evasion of human DC surveillance that could have a profound clinical
      impact upon inflammatory disease progression and highlights the need to study
      human responses to human-specific pathogens.

PMID- 20049724
TI  - The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate
      marker for Abeta42 production in the central nervous system.
AB  - Surrogate markers for the Alzheimer disease (AD)-associated 42-amino acid form of
      amyloid-beta (Abeta42) have been sought because they may aid in the diagnosis of
      AD and for clarification of disease pathogenesis. Here, we demonstrate that human
      cerebrospinal fluid (CSF) contains three APLP1-derived Abeta-like peptides
      (APL1beta) that are generated by beta- and gamma-cleavages at a concentration of
      approximately 4.5 nM. These novel peptides, APL1beta25, APL1beta27 and
      APL1beta28, were not deposited in AD brains. Interestingly, most gamma-secretase
      modulators (GSMs) and familial AD-associated presenilin1 mutants that up-regulate
      the relative production of Abeta42 cause a parallel increase in the production of
      APL1beta28 in cultured cells. Moreover, in CSF from patients with pathological
      mutations in presenilin1 gene, the relative APL1beta28 levels are higher than in
      non-AD controls, while the relative Abeta42 levels are unchanged or lower. Most
      strikingly, the relative APL1beta28 levels are higher in CSF from sporadic AD
      patients (regardless of whether they are at mild cognitive impairment or AD
      stage), than those of non-AD controls. Based on these results, we propose the
      relative level of APL1beta28 in the CSF as a candidate surrogate marker for the
      relative level of Abeta42 production in the brain.

PMID- 20049725
TI  - Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a
      biomarker and survival gene.
AB  - Understanding the biological pathways critical for common neurofibromatosis type
      1 (NF1) peripheral nerve tumours is essential, as there is a lack of tumour
      biomarkers, prognostic factors and therapeutics. We used gene expression
      profiling to define transcriptional changes between primary normal Schwann cells
      (n = 10), NF1-derived primary benign neurofibroma Schwann cells (NFSCs) (n = 22),
      malignant peripheral nerve sheath tumour (MPNST) cell lines (n = 13), benign
      neurofibromas (NF) (n = 26) and MPNST (n = 6). Dermal and plexiform NFs were
      indistinguishable. A prominent theme in the analysis was aberrant
      differentiation. NFs repressed gene programs normally active in Schwann cell
      precursors and immature Schwann cells. MPNST signatures strongly differed; genes
      up-regulated in sarcomas were significantly enriched for genes activated in
      neural crest cells. We validated the differential expression of 82 genes
      including the neural crest transcription factor SOX9 and SOX9 predicted targets.
      SOX9 immunoreactivity was robust in NF and MPSNT tissue sections and targeting
      SOX9 - strongly expressed in NF1-related tumours - caused MPNST cell death. SOX9
      is a biomarker of NF and MPNST, and possibly a therapeutic target in NF1.

PMID- 20049727
TI  - Design principles of pluripotency.

PMID- 20049728
TI  - Searching for adult stem cells in the intestine.

PMID- 20049729
TI  - Epidermal stem cell diversity and quiescence.
AB  - Mammalian epidermis is maintained by self-renewal of stem cells and terminal
      differentiation of their progeny. New data reveal a diversity amongst stem cells
      that was previously unrecognized. Different stem cell populations have different
      locations and differ in whether they are quiescent or actively cycling. During
      normal epidermal homeostasis, each stem cell population feeds a restricted number
      of differentiated lineages. However, in response to injury or genetic
      manipulation the different pools of stem cells demonstrate multi-lineage
      differentiation ability. While it is well established that Wnt signalling
      promotes hair follicle (HF) differentiation, new observations suggest a role for
      EGF receptor signalling in promoting differentiation of interfollicular
      epidermis. NFATc1 maintains quiescence in the HF, while Lrig1 exerts the same
      function in the junctional zone. The stage is now set for exploring the
      relationship between the different epidermal stem cell populations and between
      quiescence and lineage selection.

PMID- 20049730
TI  - Treating lysosomal storage diseases with pharmacological chaperones: from concept
      to clinics.
AB  - Lysosomal storage diseases (LSDs) are a group of genetic disorders due to defects
      in any aspect of lysosomal biology. During the past two decades, different
      approaches have been introduced for the treatment of these conditions. Among
      them, enzyme replacement therapy (ERT) represented a major advance and is used
      successfully in the treatment of some of these disorders. However, ERT has
      limitations such as insufficient biodistribution of recombinant enzymes and high
      costs. An emerging strategy for the treatment of LSDs is pharmacological
      chaperone therapy (PCT), based on the use of chaperone molecules that assist the
      folding of mutated enzymes and improve their stability and lysosomal trafficking.
      After proof-of-concept studies, PCT is now being translated into clinical
      applications for Fabry, Gaucher and Pompe disease. This approach, however, can
      only be applied to patients carrying chaperone-responsive mutations. The recent
      demonstration of a synergistic effect of chaperones and ERT expands the
      applications of PCT and prompts a re-evaluation of their therapeutic use and
      potential. This review discusses the strengths and drawbacks of the potential
      therapies available for LSDs and proposes that future research should be directed
      towards the development of treatment protocols based on the combination of
      different therapies to improve the clinical outcome of LSD patients.

PMID- 20049731
TI  - Partial lipodystrophy and insulin resistant diabetes in a patient with a
      homozygous nonsense mutation in CIDEC.
AB  - Lipodystrophic syndromes are characterized by adipose tissue deficiency. Although
      rare, they are of considerable interest as they, like obesity, typically lead to
      ectopic lipid accumulation, dyslipidaemia and insulin resistant diabetes. In this
      paper we describe a female patient with partial lipodystrophy (affecting limb,
      femorogluteal and subcutaneous abdominal fat), white adipocytes with
      multiloculated lipid droplets and insulin-resistant diabetes, who was found to be
      homozygous for a premature truncation mutation in the lipid droplet protein cell
      death-inducing Dffa-like effector C (CIDEC) (E186X). The truncation disrupts the
      highly conserved CIDE-C domain and the mutant protein is mistargeted and fails to
      increase the lipid droplet size in transfected cells. In mice, Cidec deficiency
      also reduces fat mass and induces the formation of white adipocytes with
      multilocular lipid droplets, but in contrast to our patient, Cidec null mice are
      protected against diet-induced obesity and insulin resistance. In addition to
      describing a novel autosomal recessive form of familial partial lipodystrophy,
      these observations also suggest that CIDEC is required for unilocular lipid
      droplet formation and optimal energy storage in human fat.

PMID- 20049732
TI  - Converting cancer mutations into therapeutic opportunities.
AB  - While the use of synthetic lethality has been around for decades in model
      organism studies, it has only recently been applied to cancer therapy and judging
      by recent results, with great success. Following on a recent paper that
      demonstrates the clinical application of this strategy (Fong et al, 2009), Chris
      Lord and Alan Ashworth further explore the approach and show that poly(ADP
      ribose) polymerase (PARP) inhibitors such as Olaparib can selectively target
      cancer cells defective in phosphatase and tensin homologue (PTEN, Mendes-Pereira
      et al, 2009) and that methotrexate is selectively lethal to MutS-homologue-2
      (MSH2)-deficient tumour cells (Martin et al, 2009).

PMID- 20049733
TI  - Hedgehog signalling in colon cancer and stem cells.
AB  - The participation of the HH pathway in colon cancer has remained controversial.
      In this issue, Varnat et al (2009) demonstrate that HH signalling is essential
      for human colon cancer growth, recurrence, metastases and stem cell expansion.
      This closeup by Gulino et al discusses the paper and its implications.

PMID- 20049734
TI  - Inflammation and EMT: an alliance towards organ fibrosis and cancer progression.
AB  - Recent advances in our understanding of the molecular pathways that govern the
      association of inflammation with organ fibrosis and cancer point to the
      epithelial to mesenchymal transition (EMT) as the common link in the progression
      of these devastating diseases. The EMT is a crucial process in the development of
      different tissues in the embryo and its reactivation in the adult may be regarded
      as a physiological attempt to control inflammatory responses and to 'heal'
      damaged tissue. However, in pathological contexts such as in tumours or during
      the development of organ fibrosis, this healing response adopts a sinister
      nature, steering these diseases towards metastasis and organ failure.
      Importantly, the chronic inflammatory microenvironment common to fibrotic and
      cancer cells emerges as a decisive factor in the induction of the pathological
      EMT.

PMID- 20049735
TI  - Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors.
AB  - The tumour suppressor gene, phosphatase and tensin homolog (PTEN), is one of the
      most commonly mutated genes in human cancers. Recent evidence suggests that PTEN
      is important for the maintenance of genome stability. Here, we show that PTEN
      deficiency causes a homologous recombination (HR) defect in human tumour cells.
      The HR deficiency caused by PTEN deficiency, sensitizes tumour cells to potent
      inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), both in
      vitro and in vivo. PARP inhibitors are now showing considerable promise in the
      clinic, specifically in patients with mutations in either of the breast cancer
      susceptibility genes BRCA1 or BRCA2. The data we present here now suggests that
      the clinical assessment of PARP inhibitors should be extended beyond those with
      BRCA mutations to a larger group of patients with PTEN mutant tumours.

PMID- 20049736
TI  - Methotrexate induces oxidative DNA damage and is selectively lethal to tumour
      cells with defects in the DNA mismatch repair gene MSH2.
AB  - Mutations in the MSH2 gene predispose to a number of tumourigenic conditions,
      including hereditary non-polyposis colon cancer (HNPCC). MSH2 encodes a protein
      in the mismatch repair (MMR) pathway which is involved in the removal of mispairs
      originating during replication or from damaged DNA. To identify new therapeutic
      strategies for the treatment of cancer arising from MMR deficiency, we screened a
      small molecule library encompassing previously utilized drugs and drug-like
      molecules to identify agents selectively lethal to cells lacking functional MSH2.
      This approach identified the drug methotrexate as being highly selective for
      cells with MSH2 deficiency. Methotrexate treatment caused the accumulation of
      potentially lethal 8-hydroxy-2'-deoxyguanosine (8-OHdG) oxidative DNA lesions in
      both MSH2 deficient and proficient cells. In MSH2 proficient cells, these lesions
      were rapidly cleared, while in MSH2 deficient cells 8-OHdG lesions persisted,
      potentially explaining the selectivity of methotrexate. Short interfering (si)RNA
      mediated silencing of the target of methotrexate, dihydrofolate reductase (DHFR),
      was also selective for MSH2 deficiency and also caused an accumulation of 8-OHdG.
      This suggested that the ability of methotrexate to modulate folate synthesis via
      inhibition of DHFR, may explain MSH2 selectivity. Consistent with this
      hypothesis, addition of folic acid to culture media substantially rescued the
      lethal phenotype caused by methotrexate. While methotrexate has been used for
      many years as a cancer therapy, our observations suggest that this drug may have
      particular utility for the treatment of a subset of patients with tumours
      characterized by MSH2 mutations.

PMID- 20049737
TI  - Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that
      is essential for tumour growth, recurrence, metastasis and stem cell survival and
      expansion.
AB  - Human colon cancers often start as benign adenomas through loss of APC, leading
      to enhanced beta CATENIN (beta CAT)/TCF function. These early lesions are
      efficiently managed but often progress to invasive carcinomas and incurable
      metastases through additional changes, the nature of which is unclear. We find
      that epithelial cells of human colon carcinomas (CCs) and their stem cells of all
      stages harbour an active HH-GLI pathway. Unexpectedly, they acquire a high
      HEDGEHOG-GLI (HH-GLI) signature coincident with the development of metastases. We
      show that the growth of CC xenografts, their recurrence and metastases require HH
      GLI function, which induces a robust epithelial-to-mesenchymal transition (EMT).
      Moreover, using a novel tumour cell competition assay we show that the self
      renewal of CC stem cells in vivo relies on HH-GLI activity. Our results indicate
      a key and essential role of the HH-GLI1 pathway in promoting CC growth, stem cell
      self-renewal and metastatic behavior in advanced cancers. Targeting HH-GLI1,
      directly or indirectly, is thus predicted to decrease tumour bulk and eradicate
      CC stem cells and metastases.

PMID- 20049740
TI  - Making the most of what you've got: optimizing residual OXPHOS function in
      mitochondrial diseases.
AB  - Patients affected by mitochondrial OXPHOS disorders are still faced with a grim
      lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent
      data by Giovanni Manfredi on PKA's functions in the mitochondria and now its
      modulation can improve respiration and ATP production in COX-defective cells.

PMID- 20049741
TI  - Neurodegenerative diseases: Lessons from genome-wide screens in small model
      organisms.
AB  - Various age-related neurodegenerative diseases, including Parkinson's disease,
      polyglutamine expansion diseases and Alzheimer's disease, are associated with the
      accumulation of misfolded proteins in aggregates in the brain. How and why these
      proteins form aggregates and cause disease is still poorly understood. Small
      model organisms--the baker's yeast Saccharomyces cerevisiae, the nematode worm
      Caenorhabditis elegans and the fruit fly Drosophila melanogaster--have been used
      to model these diseases and high-throughput genetic screens using these models
      have led to the identification of a large number of genes that modify aggregation
      and toxicity of the disease proteins. In this review, we revisit these models and
      provide a comprehensive comparison of the genetic screens performed so far. Our
      integrative analysis highlights alterations of a wide variety of basic cellular
      processes. Not all disease proteins are influenced by alterations in the same
      cellular processes and despite the unifying theme of protein misfolding and
      aggregation, the pathology of each of the age-related misfolding disorders can be
      induced or influenced by a disease-protein-specific subset of molecular
      processes.

PMID- 20049742
TI  - Cerebrospinal fluid tau and ptau(181) increase with cortical amyloid deposition
      in cognitively normal individuals: implications for future clinical trials of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) pathology is estimated to develop many years before
      detectable cognitive decline. Fluid and imaging biomarkers may identify people in
      early symptomatic and even preclinical stages, possibly when potential treatments
      can best preserve cognitive function. We previously reported that cerebrospinal
      fluid (CSF) levels of amyloid-beta(42) (Abeta(42)) serve as an excellent marker
      for brain amyloid as detected by the amyloid tracer, Pittsburgh compound B (PIB).
      Using data from 189 cognitively normal participants, we now report a positive
      linear relationship between CSF tau/ptau(181) (primary constituents of
      neurofibrillary tangles) with the amount of cortical amyloid. We observe a strong
      inverse relationship of cortical PIB binding with CSF Abeta(42) but not for
      plasma Abeta species. Some individuals have low CSF Abeta(42) but no cortical PIB
      binding. Together, these data suggest that changes in brain Abeta(42) metabolism
      and amyloid formation are early pathogenic events in AD, and that significant
      disruptions in CSF tau metabolism likely occur after Abeta(42) initially
      aggregates and increases as amyloid accumulates. These findings have important
      implications for preclinical AD diagnosis and treatment.

PMID- 20049743
TI  - Molecular aging and rejuvenation of human muscle stem cells.
AB  - Very little remains known about the regulation of human organ stem cells (in
      general, and during the aging process), and most previous data were collected in
      short-lived rodents. We examined whether stem cell aging in rodents could be
      extrapolated to genetically and environmentally variable humans. Our findings
      establish key evolutionarily conserved mechanisms of human stem cell aging. We
      find that satellite cells are maintained in aged human skeletal muscle, but fail
      to activate in response to muscle attrition, due to diminished activation of
      Notch compounded by elevated transforming growth factor beta (TGF-beta)/phospho
      Smad3 (pSmad3). Furthermore, this work reveals that mitogen-activated protein
      kinase (MAPK)/phosphate extracellular signal-regulated kinase (pERK) signalling
      declines in human muscle with age, and is important for activating Notch in human
      muscle stem cells. This molecular understanding, combined with data that human
      satellite cells remain intrinsically young, introduced novel therapeutic targets.
      Indeed, activation of MAPK/Notch restored 'youthful' myogenic responses to
      satellite cells from 70-year-old humans, rendering them similar to cells from 20
      year-old humans. These findings strongly suggest that aging of human muscle
      maintenance and repair can be reversed by 'youthful' calibration of specific
      molecular pathways.

PMID- 20049745
TI  - Novel nanostructured scaffold for osteochondral regeneration: pilot study in
      horses.
AB  - The present in vivo preliminary experiment is aimed at testing mechanical and
      biological behaviour of a new nano-structured composite multilayer biomimetic
      scaffold for the treatment of chondral and osteochondral defects. The three
      dimensional biomimetic scaffold (Fin-Ceramica Faenza S.p.A., Faenza-Italy) was
      obtained by nucleating collagen fibrils with hydroxyapatite nanoparticles, in two
      configurations, bi- and tri-layered, to reproduce, respectively, chondral and
      osteochondral anatomy. Chondral defects (lateral condyle) and deep osteochondral
      defects (medial condyle) were made in the distal epiphysis of the third
      metacarpal bone of both forelimbs of two adult horses and treated respectively
      with the chondral and osteochondral grafts. Both animals were euthanised six
      months follow up. The images obtained at the second look arthroscopy evaluation,
      performed two months after surgery, demonstrated good filling of the chondral and
      osteo-chondral defects without any inflammatory reaction around and inside the
      lesions. At the histological analysis the growth of trabecular bone in the
      osteochondral lesion was evident. Only in one case, the whole thickness of the
      osteochondral lesion was filled by fibrocartilaginous tissue. The formation of a
      tidemark line was evident at the interface with the newly formed bone. Newly
      formed fibrocartilaginous tissue was present in the area of the chondral defect.
      Initial alignment of the collagen fibres was recognisable with polarised light in
      both groups. The results of the present pilot study showed that this novel
      osteochondral and chondral scaffold may act as a suitable matrix to facilitate
      orderly regeneration of bone and hyaline-like cartilage.

PMID- 20049744
TI  - Modulation of mitochondrial protein phosphorylation by soluble adenylyl cyclase
      ameliorates cytochrome oxidase defects.
AB  - Phosphorylation of respiratory chain components has emerged as a mode of
      regulation of mitochondrial energy metabolism, but its mechanisms are still
      largely unexplored. A recently discovered intramitochondrial signalling pathway
      links CO(2) generated by the Krebs cycle with the respiratory chain, through the
      action of a mitochondrial soluble adenylyl cyclase (mt-sAC). Cytochrome oxidase
      (COX), whose deficiency causes a number of fatal metabolic disorders, is a key
      mitochondrial enzyme activated by mt-sAC. We have now discovered that the mt-sAC
      pathway modulates mitochondrial biogenesis in a reactive oxygen species dependent
      manner, in cultured cells and in animals with COX deficiency. We show that
      upregulation of mt-sAC normalizes reactive oxygen species production and
      mitochondrial biogenesis, thereby restoring mitochondrial function. This is the
      first example of manipulation of a mitochondrial signalling pathway to achieve a
      direct positive modulation of COX, with clear implications for the development of
      novel approaches to treat mitochondrial diseases.

PMID- 20049746
TI  - Immobilization of fibronectin in chitosan substrates improves cell adhesion and
      proliferation.
AB  - Covalent grafting of biomolecules is a strategy to improve the biocompatibility
      and bioactivity of materials. However, it is critical to maintain the biological
      activity of the biomolecule upon its attachment to the surface. In the present
      study we compared the biological properties of chitosan, in which the surface was
      enriched with fibronectin (Fn), using two methodologies: chemical immobilization,
      using a water-soluble carbodiimide; and simple adsorption. X-ray photoelectron
      spectroscopy studies confirmed the successful immobilization of Fn onto modified
      membranes. SaOs-2 cells were seeded onto these surfaces to assess the biological
      consequences of such modifications. The presence of Fn stimulated cell adhesion
      on chitosan. It was found that after 7 days of culture in the presence of
      covalently attached Fn, the cells are confluent; significantly fewer cells were
      detected in unmodified film and in film with adsorbed Fn. This result is
      consistent with the fact that considerable desorption of Fn from chitosan takes
      place within 24 h in culture medium. This study showed that Fn may be easily
      covalently attached onto chitosan substrates, improving the biological
      performance of the material. The technique could find applications in tissue
      engineering strategies, as the surface modification of chitosan-based substrates
      could be carried out in more complex geometries, such as in scaffolds or
      particles.

PMID- 20049747
TI  - High-resolution tissue imaging on an orbitrap mass spectrometer by desorption
      electrospray ionization mass spectrometry.

PMID- 20049748
TI  - Monoterpenoid glucoindole alkaloids and iridoids from Pterocephalus pinardii.
AB  - A new secondary metabolite, pterocephaline, along with the known cantleyoside,
      7alpha-morroniside, 3beta,5alpha-tetrahydrodesoxycordifoline lactam, 5S-5
      carboxyvincoside, sweroside, and loganin have been isolated from the aerial parts
      of P. pinardii (Dipsacaceae). Moreover, cantleyoside-methyl-hemiacetal and
      cantleyoside-dimethyl-acetal were obtained as seco-iridoid artifacts. The
      structures were elucidated by extensive spectroscopic methods including 1D-((1)H,
      (13)C and TOCSY) and 2D-NMR (DQF-COSY, HSQC and HMBC). Monoterpenoid glucoindole
      alkaloids were encountered for the first time in Dipsacaceae family.

PMID- 20049749
TI  - NMR characterization of 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate binding to
      chiral molecular micelles.
AB  - NMR spectroscopy was used to characterize the binding of the chiral compound 1,1'
      binaphthyl-2,2'-diyl hydrogen phosphate (BNP) to five molecular micelles with
      chiral dipeptide headgroups. Molecular micelles have covalent linkages between
      the surfactant monomers and are used as chiral mobile phase modifiers in
      electrokinetic chromatography. Nuclear overhauser enhancement spectroscopy
      (NOESY) analyses of (S)-BNP:molecular micelle mixtures showed that in each
      solution the (S)-BNP interacted predominately with the N-terminal amino acid of
      the molecular micelle's dipeptide headgroup. NOESY spectra were also used to
      generate group binding maps for (S)-BNP:molecular micelle mixtures. In these
      maps, percentages are assigned to the (S)-BNP protons to represent the relative
      strengths of their interactions with a specified molecular micelle proton. All
      maps showed that (S)-BNP inserted into a previously reported chiral groove formed
      between the molecular micelle's dipeptide headgroup and hydrocarbon chain. In the
      resulting intermolecular complexes, the (S)-BNP protons nearest to the analyte
      phosphate group were found to point toward the N-terminal Halpha proton of the
      molecular micelle headgroup. Finally, pulsed field gradient NMR diffusion
      experiments were used to measure association constants for (R) and (S)-BNP
      binding to each molecular micelle. These K values were then used to calculate the
      differences in the enantiomers' free energies of binding, Delta(DeltaG). The NMR
      derived Delta(DeltaG) values were found to scale linearly with electrokinetic
      chromatography (EKC) chiral selectivities from the literature.

PMID- 20049750
TI  - Robotic port-site and pelvic recurrences after robot-assisted laparoscopic
      radical hysterectomy for a stage IB1 adenocarcinoma of the cervix with negative
      lymph nodes.
AB  - BACKGROUND: Port-site metastasis (PSM) following minimally invasive surgery for
      gynaecological cancer has been recognized as a potential problem over the last
      two decades. METHODS: A 60 year-old woman with stage Ib1 adenocarcinoma of the
      cervix was treated with radical hysterectomy, bilateral salpingo-oophorectomy and
      bilateral pelvic lymph node dissection, using robot-assisted laparoscopy.
      RESULTS: Eighteen months after primary surgery, the patient developed a pelvic
      recurrence invading both the bladder mucosa and the parametrium. During the
      routine recurrence work-up, we found an 8 mm robotic port-site metastasis (PSM)
      on the abdominal computed tomography (CT) scan. CONCLUSION: This is the first
      case report emphasizing the risk of PSM and early pelvic recurrences in robot
      assisted laparoscopic radical hysterectomy and bilateral pelvic lymph node
      dissection for an early-stage cervical adenocarcinoma patient with negative lymph
      nodes, histologically examined by immunohistochemical ultrastaging.

PMID- 20049751
TI  - A Bayesian approach to joint modeling of protein-DNA binding, gene expression and
      sequence data.
AB  - The genome-wide DNA-protein-binding data, DNA sequence data and gene expression
      data represent complementary means to deciphering global and local
      transcriptional regulatory circuits. Combining these different types of data can
      not only improve the statistical power, but also provide a more comprehensive
      picture of gene regulation. In this paper, we propose a novel statistical model
      to augment protein-DNA-binding data with gene expression and DNA sequence data
      when available. We specify a hierarchical Bayes model and use Markov chain Monte
      Carlo simulations to draw inferences. Both simulation studies and an analysis of
      an experimental data set show that the proposed joint modeling method can
      significantly improve the specificity and sensitivity of identifying target genes
      as compared with conventional approaches relying on a single data source.

PMID- 20049752
TI  - Structural evolution of indomethacin particles upon milling: time-resolved
      quantification and localization of disordered structure studied by IGC and DSC.
AB  - The amorphization of indomethacin was induced by milling. The mass fraction of
      the amorphous phase in the drug milled for various time intervals was determined
      with differential scanning calorimetry (DSC). Because the surface fraction
      amorphized by milling can be much higher than the mass fraction, which can have a
      large impact on the powder properties, a method for quantification of surface
      fraction amorphized by milling using inverse gas chromatography (IGC) was
      developed. A calibration curve was constructed by mixing completely amorphous
      indomethacin (obtained after milling for 120 min) with various amounts of the
      initial crystalline sample. Linear part of the curve was then used to quantify
      the surface amorphous content of samples milled for different time intervals.
      Surface and mass amorphization kinetics were determined and fitted to a first
      order model. It was found that the surface amorphization rate is an order of
      magnitude higher than the mass amorphization rate. Results confirmed that IGC is
      a sensitive method for detection and quantification of the fraction of amorphous
      surface of milled indomethacin powder. If suitably combined with other
      techniques, this method represents a relatively general approach for the
      localization and quantification of the surface amorphous fraction in crystalline
      substances that transform into amorphous ones upon intensive milling.

PMID- 20049753
TI  - Entecavir treatment for up to 5 years in patients with hepatitis B e antigen
      positive chronic hepatitis B.
AB  - Sustained virologic suppression is a primary goal of therapy for chronic
      hepatitis B (CHB). In study entecavir (ETV)-022, 48 weeks of entecavir 0.5 mg was
      superior to lamivudine for virologic suppression for hepatitis B e antigen
      (HBeAg)-positive CHB. A total of 183 entecavir-treated patients from ETV-022
      subsequently enrolled in study ETV-901. We present the results after up to 5
      years (240 weeks) of continuous entecavir therapy. The entecavir long-term cohort
      consists of patients who received >or=1 year of entecavir 0.5 mg in ETV-022 and
      then entered ETV-901 with a treatment gap <or=35 days. In ETV-901 the entecavir
      dose was 1.0 mg daily. For patients with samples available at Year 5, proportions
      with hepatitis B virus (HBV) DNA <300 copies/mL, normal alanine aminotransferase
      (ALT) levels, HBeAg loss, and HBeAg seroconversion were determined. In all, 146
      patients met criteria for inclusion in the entecavir long-term cohort. At Year 5,
      94% (88/94) had HBV DNA <300 copies/mL and 80% (78/98) had normal ALT levels. In
      addition to patients who achieved serologic responses during study ETV-022, 23%
      (33/141) achieved HBeAg seroconversion and 1.4% (2/145) lost hepatitis B surface
      antigen (HBsAg) during study ETV-901. Through 5 years, entecavir resistance
      emerged in one patient. The safety profile of entecavir was consistent with
      previous reports. CONCLUSION: Extended therapy with entecavir through 5 years
      maintained or increased rates of HBV DNA suppression and ALT normalization.
      Additional patients also achieved HBeAg loss and seroconversion. Entecavir
      provides sustained viral suppression with minimal resistance during long-term
      treatment of HBeAg-positive CHB.

PMID- 20049754
TI  - Regioselective exohedral functionalization of La@C82 and its 1,2,3,4,5
      pentamethylcyclopentadiene and adamantylidene adducts.
AB  - The first regioselective functionalization of La@C(82) by two different groups
      has been performed. Bis-adducts of La@C(82) with Cp* and adamantylidene were
      synthesized by using two different routes and characterized. Spectroscopic
      analysis and theoretical calculations reveal that the addition position is
      controlled by the charge density and p-orbital axis vector value of the fullerene
      cage.

PMID- 20049755
TI  - Paper spray for direct analysis of complex mixtures using mass spectrometry.

PMID- 20049756
TI  - Synthesis of S-adenosyl-L-homocysteine capture compounds for selective
      photoinduced isolation of methyltransferases.
AB  - Understanding the interplay of different cellular proteins and their substrates
      is of major interest in the postgenomic era. For this purpose, selective
      isolation and identification of proteins from complex biological samples is
      necessary and targeted isolation of enzyme families is a challenging task. Over
      the last years, methods like activity-based protein profiling (ABPP) and capture
      compound mass spectrometry (CCMS) have been developed to reduce the complexity of
      the proteome by means of protein function in contrast to standard approaches,
      which utilize differences in physical properties for protein separation. To
      isolate and identify the subproteome consisting of S-adenosyl-L-methionine (SAM
      or AdoMet)-dependent methyltransferases (methylome), we developed and synthesized
      trifunctional capture compounds containing the chemically stable cofactor product
      S-adenosyl-L-homocysteine (SAH or AdoHcy) as selectivity function. SAH analogues
      with amino linkers at the N6 or C8 positions were synthesized and attached to
      scaffolds containing different photocrosslinking groups for covalent protein
      modification and biotin for affinity isolation. The utility of these SAH capture
      compounds for selective photoinduced protein isolation is demonstrated for
      various methyltransferases (MTases) acting on DNA, RNA and proteins as well as
      with Escherichia coli cell lysate. In addition, they can be used to determine
      dissociation constants for MTase-cofactor complexes.

PMID- 20049757
TI  - Temperature inhomogeneity during multibubble sonoluminescence.

PMID- 20049758
TI  - Chemical synthesis and biological screening of 2-aminoimidazole-based bacterial
      and fungal antibiofilm agents.
AB  - A collection of 2-aminoimidazole/triazole amides has been synthesized and
      screened for antibiofilm activity. This class of small molecules was found to
      modulate the biofilm activity of Pseudomonas aeruginosa, a multidrug-resistant
      strain of Acinetobacter baumannii (MDRAB), a methicillin-resistant Staphylococcus
      aureus strain (MRSA), Escherichia coli, Rhodospirillum salexigens, Staphylococcus
      epidermidis, Vibrio vulnificus, and vancomycin-resistant Enterococcus faecium as
      well as the yeast Candida albicans and Cryptococcus neoformans. Furthermore, lead
      compounds were found to not lyse red blood cells at active concentrations.

PMID- 20049759
TI  - Mutant lipase-catalyzed kinetic resolution of bulky phenyl alkyl sec-alcohols: a
      thermodynamic analysis of enantioselectivity.
AB  - The size of the stereoselectivity pocket of Candida antarctica lipase B limits
      the range of alcohols that can be resolved with this enzyme. These steric
      constrains have been changed by increasing the size of the pocket by the mutation
      W104A. The mutated enzyme has good activity and enantioselectivity toward bulky
      secondary alcohols, such as 1-phenylalkanols, with alkyl chains up to eight
      carbon atoms. The S enantiomer was preferred in contrast to the wild-type enzyme,
      which has R selectivity. The magnitude of the enantioselectivity changes in an
      interesting way with the chain length of the alkyl moiety. It is governed by
      interplay between entropic and enthalpic contributions and substrates with long
      alkyl chains are resolved best with E values higher than 100. The
      enantioselectivity increases with temperature for the small substrates, but
      decreases for the long ones.

PMID- 20049760
TI  - Glyco-scan: varying glycosylation in the sequence of the peptide hormone PYY3-36
      and its effect on receptor selectivity.
AB  - The increasing prevalence of obesity worldwide calls for safe and highly
      efficacious satiety drugs. PYY3-36 has been implicated in food intake regulation,
      and novel peptide analogues with high Y2 receptor-subtype selectivity and potency
      have potential as drugs for the treatment of obesity. It has been hypothesized
      that PYY3-36 associates with the plasma membrane prior to receptor activation
      such that the amphipathic alpha-helix of PYY3-36 possibly guides the C-terminal
      pentapeptide into the correct conformation for receptor activation. Ala-scans are
      used routinely to study the effect of individual amino acids in a given peptide
      sequence. Here we report the glyco-scan of the peptide hormone PYY3-36, in which
      hydroxyl side-chain functionalities were glycosylated; in addition new
      glycosylation sites were introduced. An array of novel PYY3-36 analogues with a
      glycan positioned in the water-membrane interface or in the N terminal were
      screened for Y-receptor affinity and selectivity as well as metabolic stability.
      Interestingly, in contrast to the Y1 and Y4 receptors, the Y2 receptor readily
      accommodated glycosylations. Especially glycosylations in the alpha-helical
      region of PYY3-36 were favorable both in terms of Y-receptor selectivity and
      endopeptidase resistance. We thus report several PYY3-36 analogues with enhanced
      Y-receptor selectivity. Our results can be used in the design of novel PYY
      analogues for the treatment of obesity. The glyco-scan concept, as systematically
      demonstrated here, has the potential for a wider applicability.

PMID- 20049761
TI  - Protection of human genomic DNA from mechanical stress by reversible folding
      transition.

PMID- 20049762
TI  - Atmospheric reactions of (H)- and (D)-fluoroalcohols with chlorine atoms.
AB  - The reactions of Cl with a series of fluoroalcohols and deuterated
      fluoroalcohols, CF(3)CH(2)OH (k(4)), CF(3)CH(OH)CH(3) (k(5)), CF(3)CH(OH)CF(3)
      (k(6)), CF(3)CH(OD)CF(3) (k(7)) and CF(3)CD(OD)CF(3) (k(8)), are investigated as
      a function of temperature in the range of 268-378 K by laser photolysis-resonance
      fluorescence. To our knowledge, only the CF(3)CH(2)OH + Cl reaction has been
      previously studied from a kinetic point of view. The derived Arrhenius
      expressions obtained using our kinetic data are: k(4) = (1.79+/-0.17) x 10(-13)
      exp[(410+/-26)/T], k(5) = (1.20+/-0.11) x 10(-12) exp[(394+/-14)/T], k(6) =
      (2.32+/-0.18) x 10(-13) exp[-(740+/-12)/T], k(7) = (6.45+/-1.87) x 10(-13) exp[
      (1136+/-94)/T] and k(8) = (4.19+/-1.09) x 10(-13) exp[-(1378+/-81)/T] (in units
      of cm(3) molecule(-1) s(-1) and where errors are +/-sigma). Moreover, a
      theoretical insight into the mechanisms of these reactions is pursued through ab
      initio Moller-Plesset second-order perturbation treatment calculations with the 6
      311G** basis set. Optimized geometries are obtained for reagents, transition
      states and molecular complexes appearing along the different reaction pathways.
      Furthermore, molecular energies are calculated at the quadratic configuration
      interaction with single, double and triple excitations [QCISD(T)] level to obtain
      an estimation of the activation energies. Finally, the rate constants are
      calculated through transition-state theory using Wigner's transmission
      coefficient in order to include the tunnelling-effect corrections.

PMID- 20049763
TI  - Calculation and measurement of terahertz active normal modes in crystalline PETN.
AB  - The terahertz frequency spectrum of pentaerythritol tetranitrate (PETN) is
      calculated using Discover with the COMPASS force field, CASTEP and PWscf. The
      calculations are compared to each other and to terahertz spectra (0.3-3 THz) of
      crystalline PETN recorded at 4 K. A number of analysis methods are used to
      characterise the calculated normal modes.

PMID- 20049764
TI  - Excited-state dynamics of the metal string complex Co3(dpa)4(NCS)2 from
      femtosecond transient absorption spectra.
AB  - Transient absorption spectroscopy is used to study the excited-state dynamics of
      Co(3)(dpa)(4)(NCS)(2), where dpa is the ligand di(2-pyridyl)amido. The pi pi*,
      charge-transfer, and d-d transition states are excited upon irradiation at
      wavelengths of 330, 400 and 600 nm, respectively. Similar transient spectra are
      observed under the experimental temporal resolution and the transient species
      show weak absorption. We thus propose that a low-lying metal-centered d-d state
      is accessed immediately after excitation. Analyses of the experimental kinetic
      traces reveal rapid conversion from the ligand-centered pi pi* and the charge
      transfer states to this metal-centered d-d state within 100 fs. The excited
      molecule then crosses to a second d-d state within the ligand-field manifold,
      with a time coefficient of 0.6-1.4 ps. Because the ground-state bleaching band
      recovers with a time coefficient of 10-23 ps, we propose that an excited molecule
      crosses from the low-lying d-d state either directly within the same spin system
      or with spin crossing via the state (2)B to the ground state (2)A(2) (symmetry
      group C(4)). In this trimetal string complex, relaxation to the ground electronic
      surface after excitation is thus rapid.

PMID- 20049765
TI  - On the reversible photoisomerization of spiropyran-modified zeolite L single
      crystals.

PMID- 20049766
TI  - Reductive splitting of cellulose in the ionic liquid 1-butyl-3-methylimidazolium
      chloride.
AB  - The depolymerization of cellulose is carried out in the ionic liquid 1-butyl-3
      methylimidazolium chloride in the presence of hydrogen gas. First, the ketal 1,1
      diethoxycyclohexane and cellobiose were used as model substrates. For the
      depolymerization of cellulose itself, the combination of a heterogeneous metal
      catalyst and a homogeneous ruthenium catalyst proved effective. One of the
      possible roles of the ruthenium compound is to enhance the transfer of hydrogen
      to the metallic surface. The cellulose is fully converted under relatively mild
      conditions, with sorbitol as the dominant product in 51-74% yield.

PMID- 20049767
TI  - The presence of functional groups key for biodegradation in ionic liquids: effect
      on gas solubility.
AB  - The effect of the incorporation of either ester or ester and ether functions into
      the side chain of an 1-alkyl-3-methylimidazolium cation on the physico-chemical
      properties of ionic liquids containing bis(trifluoromethylsulfonyl)imide or
      octylsulfate anions is studied. It is believed that the introduction of an ester
      function into the cation of the ionic liquids greatly increases their
      biodegradability. The density of three such ionic liquids is measured as a
      function of temperature, and the solubility of four gases-carbon dioxide, ethane,
      methane, and hydrogen-is determined between 303 K and 343 K and at pressures
      close to atmospheric level. Carbon dioxide is the most soluble gas, followed by
      ethane and methane; the mole fraction solubilities vary from 1.8 x 10(-3) to 3.7
      x 10(-2). These solubilities are of the same order of magnitude as those
      determined for alkylimidazolium-based ionic liquids. The chemical modification of
      the alkyl side chain does not result in a significant change of the solvation
      properties of the ionic liquid. All of the solubilities decrease with increasing
      temperature, corresponding to an exothermal solvation process. From the variation
      of this property with temperature, the thermodynamic functions of solvation
      (Gibbs energy, enthalpy, and entropy) are calculated and provide information
      about the solute-solvent interactions and the molecular structure of the
      solutions.

PMID- 20049768
TI  - Generation, capture, and utilization of industrial carbon dioxide.
AB  - As a carbon-based life form living in a predominantly carbon-based environment,
      it is not surprising that we have created a carbon-based consumer society. Our
      principle sources of energy are carbon-based (coal, oil, and gas) and many of our
      consumer goods are derived from organic (i.e., carbon-based) chemicals (including
      plastics, fabrics and materials, personal care and cleaning products, dyes, and
      coatings). Even our large-volume inorganic-chemicals-based industries, including
      fertilizers and construction materials, rely on the consumption of carbon,
      notably in the form of large amounts of energy. The environmental problems which
      we now face and of which we are becoming increasingly aware result from a human
      induced disturbance in the natural carbon cycle of the Earth caused by
      transferring large quantities of terrestrial carbon (coal, oil, and gas) to the
      atmosphere, mostly in the form of carbon dioxide. Carbon is by no means the only
      element whose natural cycle we have disturbed: we are transferring significant
      quantities of elements including phosphorus, sulfur, copper, and platinum from
      natural sinks or ores built up over millions of years to unnatural fates in the
      form of what we refer to as waste or pollution. However, our complete dependence
      on the carbon cycle means that its disturbance deserves special attention, as is
      now manifest in indicators such as climate change and escalating public concern
      over global warming. As with all disturbances in materials balances, we can seek
      to alleviate the problem by (1) dematerialization: a reduction in consumption;
      (2) rematerialization: a change in what we consume; or (3) transmaterialization:
      changing our attitude towards resources and waste. The "low-carbon" mantra that
      is popularly cited by organizations ranging from nongovernmental organizations to
      multinational companies and from local authorities to national governments is
      based on a combination of (1) and (2) (reducing carbon consumption though greater
      efficiency and lower per capita consumption, and replacing fossil energy sources
      with sources such as wind, wave, and solar, respectively). "Low carbon" is of
      inherently less value to the chemical and plastics industries at least in terms
      of raw materials although a version of (2), the use of biomass, does apply,
      especially if we use carbon sources that are renewable on a human timescale.
      There is however, another renewable, natural source of carbon that is widely
      available and for which greater utilization would help restore material balance
      and the natural cycle for carbon in terms of resource and waste. CO(2), perhaps
      the most widely discussed and feared chemical in modern society, is as
      fundamental to our survival as water, and like water we need to better understand
      the human as well as natural production and consumption of CO(2) so that we can
      attempt to get these into a sustainable balance. Current utilization of this
      valuable resource by the chemical industry is only 90 megatonne per year,
      compared to the 26.3 gigatonne CO(2) generated annually by combustion of fossil
      fuels for energy generation, as such significant opportunities exist for
      increased utilization of CO(2) generated from industrial processes. It is also
      essential that renewable energy is used if CO(2) is to be utilized as a C1
      building block.

PMID- 20049769
TI  - Robust non-linear mixed modelling of longitudinal PSA levels after prostate
      cancer treatment.
AB  - The objective of this study was to develop a robust non-linear mixed model for
      prostate-specific antigen (PSA) measurements after a high-intensity focused
      ultrasound (HIFU) treatment for prostate cancer. The characteristics of these
      data are the presence of outlying values and non-normal random effects. A
      numerical study proved that parameter estimates can be biased if these
      characteristics are not taken into account. The intra-patient variability was
      described by a Student-t distribution and Dirichlet process priors were assumed
      for non-normal random effects; a process that limited the bias and provided more
      efficient parameter estimates than a classical mixed model with normal residuals
      and random effects. It was applied to the determination of the best dynamic PSA
      criterion for the diagnosis of prostate cancer recurrence, but could be used in
      studies that rely on PSA data to improve prognosis or compare treatment
      efficiencies and also with other longitudinal biomarkers that, such as PSA,
      present outlying values and non-normal random effects.

PMID- 20049770
TI  - A review comparing the safety and tolerability of memantine with the
      acetylcholinesterase inhibitors.
AB  - OBJECTIVE: Alzheimer's disease (AD) is prevalent among elderly people, who often
      have comorbid conditions, and may be prescribed multiple medications. Drug safety
      and tolerability is paramount in maximising efficacy and optimising patient and
      carer quality of life, as patients are vulnerable to adverse events (AEs) and/or
      compliance difficulties. The two principal categories of drug used in the
      treatment of AD are the acetylcholinesterase inhibitors (AChEIs) and the NMDA
      receptor antagonist, memantine. This paper reviews the most recent safety data
      for memantine in comparison with the AChEIs. DESIGN: Review of most recent
      safety/tolerability data for memantine and AChEIs, derived from meta-analyses,
      pooled analyses, European SPCs and EMEA publications. RESULTS: Memantine was
      found to have a favourable tolerability profile when used as monotherapy or in
      combination with other agents. AChEIs were found to be fairly well tolerated. All
      treatments commonly or very commonly produce dizziness and/or headache. AChEIs
      are associated with many more types of AEs than memantine, particularly in the
      gastrointestinal category. Agitation is a less common AE when comparing memantine
      treatment to placebo, but just as common when comparing AChEI treatment to
      placebo. Withdrawals in memantine-treated groups are comparable to placebo, and
      more common in AChEI-treated groups compared to placebo. Overall, drug-drug
      interactions, contraindications and warnings were fewer for memantine than
      AChEIs. CONCLUSIONS: In both the clinical and naturalistic setting, memantine
      displays a safety and tolerability profile that is favourable and distinct from
      that of AChEIs. Safety and tolerability profiles should be given careful
      consideration when selecting treatment for AD patients.

PMID- 20049771
TI  - Mg2+ modulates integrin-extracellular matrix interaction in vascular smooth
      muscle cells studied by atomic force microscopy.
AB  - Atomic force microscopy (AFM) was used to investigate the interaction between
      alpha5beta1 integrin and fibronectin (FN) in the presence of divalent cations.
      AFM probes were labeled with FN and used to measure binding strength between
      alpha5beta1 integrin and FN by quantifying the force required to break single FN
      integrin bonds on a physiological range of loading rates (100-10,000 pN/s). The
      force necessary to rupture single alpha5beta1-FN bond increased twofold over the
      regime of loading rates investigated. Changes in Mg(2+) and Ca(2+) concentration
      affected the thermodynamical parameters of the interaction and modulated the
      binding energy. These data indicate that the external ionic environment in which
      vascular smooth muscle cells reside, influences the mechanical parameters that
      define the interaction between the extracellular matrix and integrins. Thus, in a
      dynamic mechanical environment such as the vascular wall, thermodynamic binding
      properties between FN and alpha5beta1 integrin vary in relation to locally
      applied loads and divalent cations concentrations. These changes can be recorded
      as direct measurements on live smooth muscle cells by using AFM.

PMID- 20049773
TI  - The public acceptance of nanomedicine: a personal perspective.
AB  - Limited understanding of a subject leads to limited perceptions, including
      misinformed biases and associations. In regard to the field of nanotechnology,
      prior biotechnologies have harmed public perception of nanotechnology through
      association alone. While public bias is slow to convert toward truth, it is
      likely that the medical applications of nanotechnology will foster a renewed
      interest and trust in the field through the prolonged escape from death.

PMID- 20049774
TI  - Nanotechnology and orthopedics: a personal perspective.
AB  - Bone is a nanocomposite material comprised of hierarchically arranged collagen
      fibrils, hydroxyapatite and proteoglycans in the nanometer scale. Cells are
      accustomed to interact with nanostructures, thus providing the cells with a
      natural bone-like environment that potentially enhance bone tissue
      regeneration/repair. In this direction, nanotechnology provides opportunities to
      fabricate as well as explore novel properties and phenomena of functional
      materials, devices, and systems at the nanometer-length scale. Recent studies
      have provided significant insights into the influence of topographical features
      in regulating cell behavior. Topographical features provide essential chemical
      and physical cues that cells can recognize and elicit desired cellular functions
      including preferential adhesion, migration, proliferation, and expression of
      specific cell phenotype to bring desired effects. The current article will
      address some of the nanotechnology implications in addressing issues related to
      orthopedic implants performance and tissue engineering approach to bone
      repair/regeneration.

PMID- 20049775
TI  - Prospects and developments in cell and embryo laser nanosurgery.
AB  - Recently, there has been increasing interest in the application of femtosecond
      (fs) laser pulses to the study of cells, tissues and embryos. This review
      explores the developments that have occurred within the last several years in the
      fields of cell and embryo nanosurgery. Each of the individual studies presented
      in this review clearly demonstrates the nondestructiveness of fs laser pulses,
      which are used to alter both cellular and subcellular sites within simple cells
      and more complicated multicompartmental embryos. The ability to manipulate these
      model systems noninvasively makes applied fs laser pulses an invaluable tool for
      developmental biologists, geneticists, cryobiologists, and zoologists. We are
      beginning to see the integration of this tool into life sciences, establishing
      its status among molecular and genetic cell manipulation methods. More
      importantly, several studies demonstrating the versatility of applied fs laser
      pulses have established new collaborations among physicists, engineers, and
      biologists with the common intent of solving biological problems.

PMID- 20049776
TI  - Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes
      and quantum dots.
AB  - A full understanding of the pharmacokinetic parameters describing nanomaterial
      disposition in the body would greatly facilitate development of a firm foundation
      upon which risk assessment could be based. This review focuses on the disposition
      of carbon based fullerenes and nanotubes, as well as quantum dots (QD) after
      parenteral administration to primarily rodents. The common theme across all
      particle types is that a major determinant of nanomaterial disposition is the
      degree of interaction with the reticuloendothelial (RE) cell system. Small water
      soluble particles evading this system may be excreted by the kidney. Larger
      particles and those with the proper surface charge may get targeted to RE cells
      in the liver, spleen and other organs. Most nanomaterial kinetics are
      characterized by relatively short blood half-lives reflecting tissue extraction
      and not by clearance from the body. In fact, another common attribute to
      nanomaterial kinetics is retention of particles in the body. Finally, unlike many
      small organic drugs, nanomaterials may preferentially be trafficked in the body
      via the lymphatic system that has obvious immunological implications.

PMID- 20049777
TI  - Catalyst-functionalized nanomaterials.
AB  - With rapid development in both nanotechnology and biotechnology, it is now
      possible to combine these two exciting fields to modulate the physical properties
      of nanomaterials with the molecular recognition and catalytic functional
      properties of biomolecules. Such research efforts have resulted in a larger
      number of sensors that can detect a broad range of analytes ranging from metal
      ions, small molecules, and nucleic acids down to proteins. These sensors will
      find important applications in nanomedicine. In this article, the design of
      sensors with four classes of nanomaterials (metallic, semiconductor, magnetic,
      and carbon nanotube nanoparticles) is reviewed. Metallic nanoparticles possess
      distance-dependent optical properties and are useful for designing colorimetric
      sensors. Semiconductor nanoparticles or quantum dots (QDs) appear to be superior
      alternatives to traditional organic fluorophores in many aspects, such as broad
      excitation range, narrow emission peaks, and high photo stability. QD sensors
      based on either energy transfer or charge transfer are summarized. Furthermore,
      magnetic nanoparticles are shown to be useful as smart magnetic resonance imaging
      (MRI) contrast agents. Finally, some carbon nanotubes show near-IR emission
      properties, and thus, are potentially useful for in vivo sensing. Sensors based
      on either tuning the emission intensity or wavelength are discussed.

PMID- 20049779
TI  - Informatics approaches for identifying biologic relationships in time-series
      data.
AB  - A vital goal of the genomic era is to identify biologic relationships between
      genes and gene products and to understand how these relationships influence
      phenotypes. Time course data contain a vast amount of causal and mechanistic
      information about complex systems, but experimental and informatics challenges
      must be overcome to produce and extract this information from biologic systems.
      Mathematical modeling and bioinformatics methods are being developed in
      anticipation of experiments involving the coordinated measurement of cellular and
      molecular quantities at various spatial and temporal scales. Experimental methods
      that probe at the nanoscale will facilitate the exploration of biologic systems
      at the single-cell and single-molecule level, but will also introduce special
      challenges for mathematical modeling because events at nanoscale concentrations
      are subject to the influence of intrinsic noise. This review addresses the
      progress, challenges, and frontiers in the field of time-series informatics. The
      ultimate goal of time-series informatics is to move beyond descriptive
      relationships and toward predictive models of emergent, or systemic, behaviors of
      biologic systems as a whole.

PMID- 20049778
TI  - Nanoparticle-based biologic mimetics.
AB  - Centered on solid chemistry foundations, biology and materials science have
      reached a crossroad where bottom-up designs of new biologically important
      nanomaterials are a reality. The topics discussed here present the
      interdisciplinary field of creating biological mimics. Specifically, this
      discussion focuses on mimics that are developed using various types of metal
      nanoparticles (particularly gold) through facile synthetic methods. These methods
      conjugate biologically relevant molecules, e.g., small molecules, peptides,
      proteins, and carbohydrates, in conformationally favorable orientations on the
      particle surface. These new products provide stable, safe, and effective
      substitutes for working with potentially hazardous biologicals for applications
      such as drug targeting, immunological studies, biosensor development, and
      biocatalysis. Many standard bioanalytical techniques can be used to characterize
      and validate the efficacy of these new materials, including quartz crystal
      microbalance (QCM), surface plasmon resonance (SPR), and enzyme-linked
      immunosorbent assay (ELISA). Metal nanoparticle-based biomimetics continue to be
      developed as potential replacements for the native biomolecule in applications of
      immunoassays and catalysis.

PMID- 20049780
TI  - Radioactive liposomes.
AB  - Many methods of labeling liposomes with both diagnostic and therapeutic
      radionuclides have been developed since the initial discovery of liposomes 40
      years ago. Diagnostic radiolabels can be used to track nanometer-sized liposomes
      in the body in a quantitative fashion. This article reviews the basic methods of
      single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) imaging and labeling of liposomes with single photon and dual
      photon positron emission radionuclides. Examples of the use of these diagnostic
      imaging agents will be shown. The ability to track the uptake of liposomes in
      humans and research animals on a whole body basis is providing researchers with
      an excellent tool for developing liposome-based drug delivery agents. The
      attachment of therapeutic radionuclides to liposomes also has great promise in
      cancer therapy. Recent developments in the use of liposomes carrying therapeutic
      radionuclides for cancer therapy will also be reviewed. Many of the radiolabeling
      and tracking technologies developed for nanosized liposomes will also be useful
      for the imaging and tracking of other nanoparticles.

PMID- 20049781
TI  - Magnetic resonance susceptibility based perfusion imaging of tumors using iron
      oxide nanoparticles.
AB  - Abundant preclinical and preliminary clinical data have convincingly supported
      antiangiogenic therapy as an effective strategy for the inhibition of tumor
      growth. This has led to an acute need for developing biological markers
      (biomarkers) of vascular remodeling that can be monitored in vivo, at repeated
      intervals in large numbers of patients with a variety of tumors in a noninvasive
      manner. Recently, magnetic resonance (MR) perfusion imaging with iron oxide
      nanoparticles has demonstrated the potential to be such a surrogate endpoint,
      that is, a biomarker intended to substitute for a clinical endpoint and
      predictive of clinical benefit. Consequently, both US Food and Drug
      Administration (FDA) and the National Cancer Institute (NCI) have major
      initiatives underway to improve the development of cancer therapies and the
      outcomes for cancer patients via biomarker development and evaluation. The
      biophysical principles, physiological relevance and range of imaging techniques
      underlying the success of susceptibility based contrast MR perfusion imaging with
      iron oxide nanoparticles as such a biomarker, are the subject of this review.

PMID- 20049782
TI  - Optical nanoparticle sensors for quantitative intracellular imaging.
AB  - Real-time measurements of biological/chemical/physical processes, with no
      interferences, are an ultimate goal for in vivo intracellular studies. To
      construct intracellular biosensors that meet such a goal, nanoparticle (NP)
      platforms seem to be most promising, because of their small size and excellent
      engineerability. This review describes the development of NP-based opical sensors
      and their intracellular applications. The sensor designs are classified into two
      types, based on the sensor structures regarding analyte receptor and signal
      transducer. Type 1 sensors, with a single component for both receptor and
      transducer, work by mechanisms similar to those of 'molecular probes'. Type 2
      sensors, with a separate component for receptor and transducer, work by different
      mechanisms that require the presence of specific NPs. A synergistic increase in
      optical signal or selectivity has been reported for these second type of NP
      sensors. With ongoing rapid advances in nanotechnology and instrumentation, these
      NP systems will soon be capable of sensing at the single-molecule level, at the
      point of interest within the living cell, and capable of simultaneously detecting
      multiple analytes and physical parameters.

PMID- 20049783
TI  - Synthesis of poly(alkyl cyanoacrylate)-based colloidal nanomedicines.
AB  - Nanoparticles developed from poly(alkyl cyanoacrylate) (PACA) biodegradable
      polymers have opened new and exciting perspectives in the field of drug delivery
      due to their nearly ideal characteristics as drug carriers in connection with
      biomedical applications. Thanks to the direct implication of organic chemistry,
      polymer science and physicochemistry, multiple PACA nanoparticles with different
      features can be obtained: nanospheres and nanocapsules (either oil- or water
      containing) as well as long-circulating and ligand-decorated nanoparticles. This
      review aims at emphasizing the synthetic standpoint of all these nanoparticles by
      describing the important aspects of alkyl cyanoacrylate chemistry as well as the
      experimental procedures and the different techniques involved for the preparation
      of the corresponding colloidal devices.

PMID- 20049784
TI  - Hydrogel mediated delivery of trophic factors for neural repair.
AB  - Neurotrophins have been implicated in a variety of diseases and their delivery to
      sites of disease and injury has therapeutic potential in applications including
      spinal cord injury, Alzheimer's disease, and Parkinson's disease. Biodegradable
      polymers, and specifically, biodegradable water-swollen hydrogels, may be
      advantageous as delivery vehicles for neurotrophins because of tissue-like
      properties, tailorability with respect to degradation and release behavior, and a
      history of biocompatibility. These materials may be designed to degrade via
      hydrolytic or enzymatic mechanisms and can be used for the sustained delivery of
      trophic factors in vivo. Hydrogels investigated to date include purely synthetic
      to purely natural, depending on the application and intended release profiles.
      Also, flexibility in material processing has allowed for the investigation of
      injectable materials, the development of scaffolding and porous conduits, and the
      use of composites for tailored molecule delivery profiles. It is the objective of
      this review to describe what has been accomplished in this area thus far and to
      remark on potential future directions in this field. Ultimately, the goal is to
      engineer optimal biomaterials to deliver molecules in a controlled and dictated
      manner that can promote regeneration and healing for numerous neural
      applications.

PMID- 20049785
TI  - Mesoporous silica-based nanomaterials for drug delivery: evaluation of structural
      properties associated with release rate.
AB  - We present here a study of the controlled release of amino acid-derived
      amphiphilic molecules from the internal pore structure of mesoporous nanoparticle
      drug delivery systems with different structural properties, namely cubic and
      hexagonal structures of various degrees of complexity. The internal pore surface
      of the nanomaterials presented has been functionalised with amine moieties
      through a one-pot method. Release profiles obtained by conductivity measurements
      are interpreted in terms of specific structural and textural parameters of the
      porous nanoparticles, such as pore geometry and connectivity. Results indicate
      that diffusion coefficients are lower by as much 4 orders of magnitude in two
      dimensional structures in comparison to three-dimensional mesoporous solids. A
      fast release in turn is observed from mesocaged materials AMS-9 and AMS-8, where
      the presence of structural defects is thought to lead to a slightly lower
      diffusion coefficient in the latter. We conclude that the use of single or mixed
      phases of these porous systems can be utilized to provide sustained release over
      long time periods and expect their use in a variety of formulations.

PMID- 20049786
TI  - Current status of nanotechnology approaches for cardiovascular disease: a
      personal perspective.
AB  - Nanotechnology is poised to have an increasing impact on cardiovascular health in
      coming years. Diagnostically, multiplexed point-of-care devices will enable rapid
      genotyping and biomarker measurement to optimize and tailor therapies for the
      individual patient. Nanoparticle-based molecular imaging agents will take
      advantage of targeted agents to provide increased insight into disease pathways
      rather then simply providing structural and functional information. Drug delivery
      will be impacted by targeting of nanoparticle-encapsulated drugs to the site of
      action, increasing the effective concentration and decreasing systemic dosage and
      side effects. Controlled and tailored release of drugs from polymers will improve
      control of pharmacokinetics and bioavailability. The application of
      nanotechnology to tissue engineering will facilitate the fabrication of better
      tissue implants in vitro, and provide scaffolds to promote regeneration in vivo
      taking advantage of the body's own repair mechanisms. Medical devices will
      benefit from the development of nanostructured surfaces and coatings to provide
      better control of thrombogenicity and infection. Taken together, these new
      technologies have enormous potential for improving the diagnosis and treatment of
      cardiovascular diseases.

PMID- 20049788
TI  - Nanoscale imaging of microbial pathogens using atomic force microscopy.
AB  - The nanoscale exploration of microbes using atomic force microscopy (AFM) is an
      exciting research field that has expanded rapidly in the past years. Using AFM
      topographic imaging, investigators can visualize the surface structure of live
      cells under physiological conditions and with unprecedented resolution. In doing
      so, the effect of drugs and chemicals on the fine cell surface architecture can
      be monitored. Real-time imaging offers a means to follow dynamic events such as
      cell growth and division. In parallel, chemical force microscopy (CFM), in which
      AFM tips are modified with specific functional groups, allows researchers to
      measure interaction forces, such as hydrophobic forces, and to resolve nanoscale
      chemical heterogeneities on cells, on a scale of only approximately 25 functional
      groups. Lastly, molecular recognition imaging using spatially resolved force
      spectroscopy, dynamic recognition imaging or immunogold detection, enables
      microscopists to localize specific receptors, such as cell adhesion proteins or
      antibiotic binding sites. These noninvasive nanoscale analyses provide new
      avenues in pathogenesis research, particularly for investigating the action mode
      of antimicrobial drugs, and for elucidating the molecular basis of pathogen-host
      interactions.

PMID- 20049787
TI  - In vivo fluorescence imaging: a personal perspective.
AB  - In vivo fluorescence imaging with near-infrared (NIR) light holds enormous
      potential for a wide variety of molecular diagnostic and therapeutic
      applications. Because of its quantitative sensitivity, inherent biological
      safety, and relative ease of use (i.e., with respect to cost, time, mobility, and
      its familiarity to a diverse population of investigators), fluorescence-based
      imaging techniques are being increasingly utilized in small-animal research.
      Moreover, there is substantial interest in the translation of novel optical
      techniques into the clinic, where they will prospectively aid in noninvasive and
      quantitative screening, disease diagnosis, and post-treatment monitoring of
      patients. Effective deep-tissue fluorescence imaging requires the application of
      exogenous NIR-emissive contrast agents. Currently, available probes fall into two
      major categories: organic and inorganic NIR fluorophores (NIRFs). In the studies
      reviewed herein, we utilized polymersomes (50 nm to 50 microm diameter polymer
      vesicles) for the incorporation and delivery of large numbers of highly emissive
      oligo (porphyrin)-based, organic NIRFs.

PMID- 20049789
TI  - Ferritin nanoparticles as magnetic resonance reporter gene.
AB  - Dynamic imaging of gene expression in live animals is among the exciting
      challenges of molecular imaging. To achieve that, one of the approaches is to use
      reporter genes that encode for the synthesis of easily detectable products. Such
      reporter genes can be designed to be expressed under the control of the
      regulatory elements included in a promoter region of a gene of interest, thus
      allowing the use of the same reporter gene for the detection of multiple genes.
      The most commonly used reporter genes include the firefly light-generating enzyme
      luciferase and the green fluorescent protein detectable by bioluminescence and
      fluorescence optical imaging, respectively. Over the last years a number of
      studies demonstrated the ability to use the iron-binding protein ferritin as a
      reporter gene that allows the detection of gene expression by magnetic resonance
      imaging (MRI). MRI provides high spatial resolution and soft tissue contrast for
      deep tissues along with a large arsenal of functional and anatomical contrast
      mechanisms that can be correlated with gene expression, and can potentially be
      translated into clinical use.

PMID- 20049790
TI  - Commercialization of nanotechnology.
AB  - The emerging and potential commercial applications of nanotechnologies clearly
      have great potential to significantly advance and even potentially revolutionize
      various aspects of medical practice and medical product development.
      Nanotechnology is already touching upon many aspects of medicine, including drug
      delivery, diagnostic imaging, clinical diagnostics, nanomedicines, and the use of
      nanomaterials in medical devices. This technology is already having an impact;
      many products are on the market and a growing number is in the pipeline. Momentum
      is steadily building for the successful development of additional nanotech
      products to diagnose and treat disease; the most active areas of product
      development are drug delivery and in vivo imaging. Nanotechnology is also
      addressing many unmet needs in the pharmaceutical industry, including the
      reformulation of drugs to improve their bioavailability or toxicity profiles. The
      advancement of medical nanotechnology is expected to advance over at least three
      different generations or phases, beginning with the introduction of simple
      nanoparticulate and nanostructural improvements to current product and process
      types, then eventually moving on to nanoproducts and nanodevices that are limited
      only by the imagination and limits of the technology itself. This review looks at
      some recent developments in the commercialization of nanotechnology for various
      medical applications as well as general trends in the industry, and explores the
      nanotechnology industry that is involved in developing medical products and
      procedures with a view toward technology commercialization.

PMID- 20049791
TI  - Occupational exposure to nanomedical applications.
AB  - Applications of nanotechnology in medicine such as cancer treatment drugs,
      imaging agents, and sensors promise to save people's lives and improve quality of
      life. Although only a limited number of nano-enabled medical applications are
      commercially available at this time, many are in the final stages of approval by
      regulatory agencies overseeing medical applications. Workers' exposure to nano
      enabled medical applications in research and development laboratories and
      manufacturing facilities can already occur. This article reviews the information
      available on exposure to nano-enabled medical applications in occupational
      settings such as manufacturing and health care facilities. First, this report
      reviews monitoring exposure to conventional medical applications. Next, it
      describes monitoring exposure to nanomaterials. And, finally, it summarizes
      monitoring exposure to nano-enabled medical applications highlighting their
      unique aspects.

PMID- 20049792
TI  - Noise in biological circuits.
AB  - Noise biology focuses on the sources, processing, and biological consequences of
      the inherent stochastic fluctuations in molecular transitions or interactions
      that control cellular behavior. These fluctuations are especially pronounced in
      small systems where the magnitudes of the fluctuations approach or exceed the
      mean value of the molecular population. Noise biology is an essential component
      of nanomedicine where the communication of information is across a boundary that
      separates small synthetic and biological systems that are bound by their size to
      reside in environments of large fluctuations. Here we review the fundamentals of
      the computational, analytical, and experimental approaches to noise biology. We
      review results that show that the competition between the benefits of low noise
      and those of low population has resulted in the evolution of genetic system
      architectures that produce an uneven distribution of stochasticity across the
      molecular components of cells and, in some cases, use noise to drive biological
      function. We review the exact and approximate approaches to gene circuit noise
      analysis and simulation, and review many of the key experimental results obtained
      using flow cytometry and time-lapse fluorescent microscopy. In addition, we
      consider the probative value of noise with a discussion of using measured noise
      properties to elucidate the structure and function of the underlying gene
      circuit. We conclude with a discussion of the frontiers of and significant future
      challenges for noise biology.

PMID- 20049794
TI  - Using nanoparticles to push the limits of detection.
AB  - The size-dependent chemical and physical properties of nanoparticles inspire the
      design of unique assays and the use of new detection schemes while also offering
      the opportunity to vastly improve the results achieved when using traditional
      signal transduction methods. Herein, the most commonly exploited nanoparticle
      amplification schemes are organized and reviewed on the basis of the detection
      methods used to monitor the nanoparticle property of interest. The topics covered
      include the improved signal photostability and brightness of semiconductor
      quantum dots, the increased extinction coefficient of noble metal nanoparticles,
      the advantages of having a magnetic label on individual target molecules to
      facilitate separation, the multiplexing that is enabled with 'barcoded'
      nanoparticles, and the greatly amplified signals that can be achieved on the
      basis of conductivity changes, generated current, or simply by adding a 'massive'
      nanoparticle onto a small molecule target. Common approaches emerge among
      different nanoparticle materials and detection schemes, and it is also clear that
      there is still significant opportunity to use nanoparticles in as-yet-unimagined
      ways to further improve assay and sensor limits of detection.

PMID- 20049793
TI  - Nanostructured polymer scaffolds for tissue engineering and regenerative
      medicine.
AB  - The structural features of tissue engineering scaffolds affect cell response and
      must be engineered to support cell adhesion, proliferation and differentiation.
      The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells
      interact with prior to forming a new tissue. In this review, bone tissue
      engineering is used as the primary example for the sake of brevity. We focus on
      nanofibrous scaffolds and the incorporation of other components including other
      nanofeatures into the scaffold structure. Since the ECM is comprised in large
      part of collagen fibers, between 50 and 500 nm in diameter, well-designed
      nanofibrous scaffolds mimic this structure. Our group has developed a novel
      thermally induced phase separation (TIPS) process in which a solution of
      biodegradable polymer is cast into a porous scaffold, resulting in a nanofibrous
      pore-wall structure. These nanoscale fibers have a diameter (50-500 nm)
      comparable to those collagen fibers found in the ECM. This process can then be
      combined with a porogen leaching technique, also developed by our group, to
      engineer an interconnected pore structure that promotes cell migration and tissue
      ingrowth in three dimensions. To improve upon efforts to incorporate a ceramic
      component into polymer scaffolds by mixing, our group has also developed a
      technique where apatite crystals are grown onto biodegradable polymer scaffolds
      by soaking them in simulated body fluid (SBF). By changing the polymer used, the
      concentration of ions in the SBF and by varying the treatment time, the size and
      distribution of these crystals are varied. Work is currently being done to
      improve the distribution of these crystals throughout three-dimensional scaffolds
      and to create nanoscale apatite deposits that better mimic those found in the
      ECM. In both nanofibrous and composite scaffolds, cell adhesion, proliferation
      and differentiation improved when compared to control scaffolds. Additionally,
      composite scaffolds showed a decrease in incidence of apoptosis when compared to
      polymer control in bone tissue engineering. Nanoparticles have been integrated
      into the nanostructured scaffolds to deliver biologically active molecules such
      as growth and differentiation factors to regulate cell behavior for optimal
      tissue regeneration.

PMID- 20049795
TI  - Nanomedicine for respiratory diseases.
AB  - Treatment of respiratory diseases and infections has proved to be a challenging
      task, with the incidence of these ailments increasing worldwide. Nanotechnology
      based drug and gene delivery systems offer a possible solution to some of the
      shortfalls of the current treatment regimen. Nanobased drug delivery systems have
      revolutionised the field of pharmacotherapy by presenting the ability to alter
      the pharmacokinetics of the conventional drugs to extend the drug retention time,
      reduce the toxicity and increase the half-life of the drugs. Delivery of
      exogenous genes to the airway epithelium in vivo has been limited by several
      physiological barriers, resulting in the low success rate of these systems. With
      the advent of nanotechnology, DNA compacted with cationic polymers to produce
      nanoparticles has exhibited a significant increase in the transfection
      efficiencies. With nanoparticulate drug/gene delivery systems, specific cells can
      be targeted by functionalising the polymeric nanoparticles with ligands that
      allow the particles to dock at a specific site of the cell. In addition,
      polymeric systems allow for the cargo to be released in a controlled and stimuli
      responsive manner. The advantages that nanoparticulate delivery systems present
      in the treatment of respiratory diseases and infections are summarised in this
      review.

PMID- 20049796
TI  - Nanoparticle therapeutics: a personal perspective.
AB  - Nanotechnology offers many potential benefits to cancer research through passive
      and active targeting, increased solubility/bioavailablility, and novel therapies.
      However, preclinical characterization of nanoparticles is complicated by the
      variety of materials, their unique surface properties, reactivity, and the task
      of tracking the individual components of multicomponent, multifunctional
      nanoparticle therapeutics in in vivo studies. There are also regulatory
      considerations and scale-up challenges that must be addressed. Despite these
      hurdles, cancer research has seen appreciable improvements in efficacy and quite
      a decrease in the toxicity of chemotherapeutics because of 'nanotech'
      formulations, and several engineered nanoparticle clinical trials are well
      underway. This article reviews some of the challenges and benefits of
      nanomedicine for cancer therapeutics and diagnostics.

PMID- 20049797
TI  - In vivo visualization of macrophage infiltration and activity in inflammation
      using magnetic resonance imaging.
AB  - Because macrophages play a key role on host defense, visualization of the
      migration of these cells is of high relevance for both diagnostic purposes and
      the evaluation of therapeutic interventions. The present article addresses the
      use of iron oxide and gadolinium-based particles for the noninvasive in vivo
      detection of macrophage infiltration into inflamed areas by magnetic resonance
      imaging (MRI). A general introduction on the functions and general
      characteristics of macrophages is followed by a discussion of some of the agents
      and acquisition schemes currently used to track the cells in vivo. Attention is
      then devoted to preclinical and clinical applications in the following disease
      areas: atherosclerosis and myocardial infarction, stroke, multiple sclerosis,
      rheumatoid arthritis, and kidney transplantation.

PMID- 20049798
TI  - Magnetic resonance relaxation properties of superparamagnetic particles.
AB  - Nanometric crystals of maghemite are known to exhibit superparamagnetism. Because
      of the significance of their magnetic moment, maghemite nanoparticles are
      exceptional contrast agents and are used for magnetic resonance imaging (of the
      liver, spleen, lymph nodes), for magnetic resonance angiography and for molecular
      and cellular imaging. The relaxivity of these agents depends on their size,
      saturation magnetization and magnetic field and also on their degree of
      clustering. There are different types of maghemite particles whose relaxation
      characteristics are suited to a specific MRI application. The relaxation induced
      by maghemite particles is caused by the diffusion of water protons in the
      inhomogeneous field surrounding the particles. This is well described by a
      theoretical model that takes magnetite crystal anisotropy and Neel relaxation
      into account. Another type of superparamagnetic compound is ferritin, the iron
      storing protein: it contains a superparamagnetic ferrihydrite core. Even if the
      resulting magnetic moment of ferritin is far smaller than for magnetite
      nanoparticles, its massive presence in different organs darkens T(2)-weighted MR
      images, allowing the noninvasive estimation of iron content, thanks to MRI. The
      relaxation induced by ferritin in aqueous solutions has been demonstrated to be
      caused by the exchange of protons between bulk water protons and the surface of
      the ferrihydrite crystal. However, in vivo, the relaxation properties of ferritin
      are still unexplained, probably because of protein clustering.

PMID- 20049799
TI  - Anti-angiogenic perfluorocarbon nanoparticles for diagnosis and treatment of
      atherosclerosis.
AB  - Complementary developments in nanotechnology, genomics, proteomics, molecular
      biology and imaging offer the potential for early, accurate diagnosis.
      Molecularly-targeted diagnostic imaging agents will allow noninvasive phenotypic
      characterization of pathologies and, therefore, tailored treatment close to the
      onset. For atherosclerosis, this includes anti-angiogenic therapy with
      specifically-targeted drug delivery systems to arrest the development of plaques
      before they impinge upon the lumen. Additionally, monitoring the application and
      effects of this targeted therapy in a serial fashion will be important. This
      review covers the specific application of alpha(nu)beta(3)-targeted anti
      angiogenic perfluorocarbon nanoparticles in (1) the detection of molecular
      markers for atherosclerosis, (2) the immediate verification of drug delivery with
      image-based prediction of therapy outcomes, and (3) the serial, noninvasive
      observation of therapeutic efficacy.

PMID- 20049800
TI  - Cell-targeting and cell-penetrating peptides for delivery of therapeutic and
      imaging agents.
AB  - This review will discuss the basic concepts concerning the use of cell-targeting
      peptides (CTPs) and cell-penetrating peptides (CPPs) in the context of
      nanocarrier technology. It deals with the discovery and subsequent evolution of
      CTPs and CPPs, issues concerning their interactions with cells and their
      biodistribution in vivo, and their potential advantages and disadvantages as
      delivery agents. The article also briefly discusses several specific examples of
      the use of CTPs or CPPs to assist in the delivery of nanoparticles, liposomes,
      and other nanocarriers.

PMID- 20049801
TI  - Nanotechnology for bone materials.
AB  - It has been established that for orthopedic-related research, nanomaterials
      (materials defined as those with constituent dimensions less than 100 nm in at
      least one direction) have superior properties compared to conventional
      counterparts. This review summarizes studies that have demonstrated enhanced in
      vitro and in vivo osteoblast (bone-forming cells) functions (such as adhesion,
      proliferation, synthesis of bone-related proteins, and deposition of calcium
      containing mineral) on nanostructured metals, ceramics, polymers, and composites
      thereof compared to currently used implants. These results strongly imply that
      nanomaterials may improve osseointegration, which is crucial for long-term
      implant efficacy. This review also focuses on novel drug-carrying magnetic
      nanoparticles designed to treat various bone diseases (such as osteoporosis).
      Although further investigation of the in vivo responses and toxicity of these
      novel nanomaterials pertinent for orthopedic applications are needed,
      nanotechnology clearly has already demonstrated the ability to produce better
      bone implants and therefore should be further investigated.

PMID- 20049802
TI  - Nanotoxicology: a personal perspective.
AB  - Nanoparticles arise from a wide variety of natural and man-made sources and have
      a diverse array of biological, chemical, and physical properties. The toxicity of
      these particles can be roughly divided into two categories: 1) the enhanced
      delivery of toxic agents 2) toxicity induced the properties of the particle
      itself. The use of nanoparticles to provide enhanced delivery of
      chemotherapeutics is presented followed by a discussion of the size-based effects
      of electron transfer and physical membrane disruption.

PMID- 20049803
TI  - Nanoparticles for photoacoustic imaging.
AB  - Nanoparticles have been designed and applied as contrast enhancers in various
      optical imaging techniques, such as optical coherence tomography, fluorescence
      imaging, and optical reflectance microscopy. As an emerging hybrid imaging
      modality, photoacoustic imaging (PAI) has also benefited from the application of
      these nanoparticle-based contrast agents. We review this rapidly growing field
      and describe the applications of nanoparticles in PAI. Particular focus is given
      to nanoparticles whose absorption mechanism is based on surface plasmon
      resonance, including gold nanoshells, nanorods, and nanocages. Dye-embedded
      nanoparticles are also reviewed. Specifically, the design and application of each
      nanoparticle-based contrast agent in relation to the field of PAI are detailed.

PMID- 20049804
TI  - Nanofibrous composites for tissue engineering applications.
AB  - Development of artificial matrices for tissue engineering is a crucial area of
      research in the field of regenerative medicine. Successful tissue scaffolds, in
      analogy with the natural mammalian extracellular matrix (ECM), are multi
      component, fibrous, and on the nanoscale. In addition, to this key morphology,
      artificial scaffolds must have mechanical, chemical, surface, and electrical
      properties that match the ECM or basement membrane of the specific tissue
      desired. In particular, these material properties may vary significantly for the
      four primary tissues in the body: nerve, muscle, epithelial, and connective. In
      order to address this complex array of attributes with a polymeric material, a
      nanocomposite approach, employing a blend of materials, addition of a particle to
      enhance particular properties, or a surface treatment, is likely to be required.
      In this review, we examine nanocomposite approaches to address these diverse
      needs as a function of tissue type. The review is intended as a bridge between
      material scientists and biomedical researchers to give basic background
      information on tissue biology to the former, and on material processing
      approaches to the latter, in a general manner, and specifically review fibrous
      nanocomposite materials that have previously been used for cell studies, either
      in vivo or in vitro.

PMID- 20049805
TI  - Top-down particle fabrication: control of size and shape for diagnostic imaging
      and drug delivery.
AB  - This review discusses rational design of particles for use as therapeutic vectors
      and diagnostic imaging agent carriers. The emerging importance of both particle
      size and shape is considered, and the adaptation and modification of soft
      lithography methods to produce nanoparticles are highlighted. To this end,
      studies utilizing particles made via a process called Particle Replication In Non
      wetting Templates are discussed. In addition, insights gained into therapeutic
      cargo and imaging agent delivery from related types of polymer-based carriers are
      considered.

PMID- 20049806
TI  - Nanoparticle vaccines against respiratory viruses.
AB  - Influenza virus, respiratory syncytial virus (RSV), and parainfluenza type 3
      virus (PI-3V) are the major viral agents which are consistently involved in
      causing lower respiratory tract disease in humans and animals. The virus
      infection begins in the upper respiratory tract, where immune responses are
      initiated, and then progresses to the lower respiratory tract where destruction
      of cells and tissues leads to bronchitis, bronchiolitis, and pneumonia, which is
      occasionally fatal. Nanoparticle vaccines, incorporating antigenic components
      from influenza, RSV, or PI-3V have been shown to be capable of stimulating
      mucosal and systemic immune responses, which can prevent the spread of infection
      to the lower respiratory tract. The encapsulation of viral proteins within
      nanoparticles may also facilitate production of respiratory vaccines which are
      efficacious in infants, where presence of maternally derived antibodies can
      reduce vaccine efficacy.

PMID- 20049807
TI  - Dextran-doxorubicin/chitosan nanoparticles for solid tumor therapy.
AB  - Chemotherapy is a major therapeutic approach for the treatment of localized and
      metastasized cancers. Whereas potent chemotherapeutic agents seem promising in
      the test tube, clinical trials often fail due to unfavorable pharmacokinetics,
      poor delivery, low local concentrations, and limited accumulation in the target
      cell. The pathophysiology of the tumor vasculature and stromal compartment
      presents a major obstacle to effective delivery of agents to solid tumors. Poor
      perfusion of the tumor, arterio-venous shunting, necrotic and hypoxic areas, as
      well as a high interstitial fluid pressure work against favorable drug uptake.
      Thus, targeted drug delivery using long-circulating particulate drug carriers
      such as hydrogels of controlled size (<100 nm diameter) holds immense potential
      to improve the treatment of cancer by selectively providing therapeutically
      effective drug concentrations at the tumor site [through enhanced permeability
      and retention (EPR) effect] while reducing undesirable side effects. This review
      focuses on the progress of targeted delivery of nanoparticulated anticancer drug
      such as doxorubicin chemically conjugated with dextran and encapsulated in
      chitosan nanoparticles to solid tumor with reduced side effect of drug. Regulated
      particle size and long circulation of these hydrogel nanoparticles in blood help
      them accumulate in tumor tissue through EPR effect as evident from the
      significant regression of the tumor volume. The cardiotoxicity of doxorubicin can
      be minimized by coupling the drug with dextran and encapsulating it in chitosan
      nanoparticles.

PMID- 20049808
TI  - Moving toward exposure and risk evaluation of nanomaterials: challenges and
      future directions.
AB  - Nanotechnology, the commercial development of engineered nanomaterials, promises
      breakthrough innovations by enhancing the performance of existing consumer
      products and enabling development of new devices, architectures, and
      applications. Although these materials and applications are being developed at an
      explosive pace, a fundamental understanding of any potential human health and
      environmental risks resulting from exposure throughout the lifecycle of these
      materials has not advanced as rapidly. Past experience has demonstrated that
      successful introduction of a new technology occurs more readily if it is
      precipitated by a robust appreciation for any inherent risks associated with the
      technology. Such understanding allows the timely development of occupational and
      consumer exposure standards that might be needed to protect human health and the
      environment. Although risk is recognized as the product of hazard and exposure,
      too often exposure patterns are poorly characterized, and risk is based primarily
      or exclusively on the hazard characterization. The extent of exposure to
      nanomaterials in currently available commercial products is relatively unknown.
      Given the number of commercial products that claim to contain engineered
      nanomaterials, it is possible that human and environmental exposure to these
      materials is widespread. This paper is intended to highlight the importance of
      exposure assessment for determining the potential risks of nanomaterials. In
      essence, this is a call to action to the community of exposure scientists,
      toxicologists, and risk assessors to develop, consider, and incorporate requisite
      exposure information in the risk assessment of nanomaterials. Without an
      integrated approach, it will be difficult to meaningfully assess the risks of
      nanomaterials, realize their potential benefits, and foster their sustainable
      development.

PMID- 20049810
TI  - Drug-eluting stent coatings.
AB  - This paper reviews the development of coronary stents from a polymer scientist's
      view point, and presents the first results of an interdisciplinary team assembled
      for the development of new stent systems. Poly(styrene-b-isobutylene-b-styrene)
      block copolymer (SIBS), a nanostructured thermoplastic elastomer, is used in
      clinical practice as the drug-eluting polymeric coating on the Taxus coronary
      stent (trademark of Boston Scientific Co.). Our group has been developing new
      architectures comprising of arborescent (dendritic) polyisobutylene cores
      (D_SIBS), which were shown to be as biocompatible as SIBS. ElectroNanospray
      (Nanocopoeia Inc.) was used to coat test coupons and coronary stents with
      selected D(S)IBS polymers loaded with dexamethasone, a model drug. The surface
      topology varied from smooth to nanosized particulate coating. This paper will
      demonstrate how drug release profiles were influenced by both the molecular
      weight of the polyisobutylene core and spraying conditions of the polymer-drug
      mixture.

PMID- 20049811
TI  - Polyalkylcyanoacrylate nanoparticles for delivery of drugs across the blood-brain
      barrier.
AB  - The major problem in drug delivery to the brain is the presence of the blood
      brain barrier (BBB) which limits drug penetration even if in certain pathological
      situations the BBB is partly disrupted. Among noninvasive techniques to overcome
      this barrier, the use of nanoparticles has been proposed. This review focuses on
      poly(alkylcyanoacrylates) (PACA)-based nanoparticles which have been developed
      for brain targeting. Both types of 'stealth' PACA nanoparticles with modified
      surface, those coated with surfactant and those with chains of polyethylene
      glycol (PEG) linked to the hydrophobic core of PACA are presented. The synthesis
      of polymers, the preparation of nanoparticles with modified surface and their
      physicochemical characterization are described. The review of their in vivo
      results evidenced their ability to enter into the brain using healthy animals or
      models of central nervous system (CNS) diseases. The nature of the surface
      modification (surfactant nature, PEG linkage, drug loading interference) seems to
      have a great influence on the efficacy of brain targeting which can be related to
      the adsorption of some apolipoproteins (Apo E, B, A-I). The mechanism of their
      passage through the BBB has been studied by in vitro and in vivo experiments,
      which suggested the implication of receptor-mediated endocytosis processes.
      According to these data, some antibodies (OX26) and ligands (transferrin, Apo
      E/B/A-I) seem to be good candidates to be coupled with 'stealth' PACA
      nanoparticles in order to increase their passage through the BBB and to promote
      active targeting to the brain.

PMID- 20049809
TI  - Physicochemical factors that affect metal and metal oxide nanoparticle passage
      across epithelial barriers.
AB  - The diversity of nanomaterials in terms of size, shape, and surface chemistry
      poses a challenge to those who are trying to characterize the human health and
      environmental risks associated with incidental and unintentional exposures. There
      are numerous products that are already commercially available that contain solid
      metal and metal oxide nanoparticles, either embedded in a matrix or in solution.
      Exposure assessments for these products are often incomplete or difficult due to
      technological challenges associated with detection and quantitation of
      nanoparticles in gaseous or liquid carriers. The main focus of recent research
      has been on hazard identification. However, risk is a product of hazard and
      exposure, and one significant knowledge gap is that of the target organ dose
      following in vivo exposures. In order to reach target organs, nanoparticles must
      first breach the protective barriers of the respiratory tract, gastrointestinal
      tract, or skin. The fate of those nanoparticles that reach physiological barriers
      is in large part determined by the properties of the particles and the barriers
      themselves. This article reviews the physiological properties of the lung, gut,
      and skin epithelia, the physicochemical properties of metal and metal oxide
      nanoparticles that are likely to affect their ability to breach epithelial
      barriers, and what is known about their fate following in vivo exposures.

PMID- 20049812
TI  - Magnetic quantum dots for multimodal imaging.
AB  - Multimodal contrast agents based on highly luminescent quantum dots (QDs)
      combined with magnetic nanoparticles (MNPs) or ions form an exciting class of new
      materials for bioimaging. With two functionalities integrated in a single
      nanoparticle, a sensitive contrast agent for two very powerful and highly
      complementary imaging techniques [fluorescence imaging and magnetic resonance
      imaging (MRI)] is obtained. In this review, the state of the art in this rapidly
      developing field is given. This is done by describing the developments for four
      different approaches to integrate the fluorescence and magnetic properties in a
      single nanoparticle. The first type of particles is created by the growth of
      heterostructures in which a QD is either overgrown with a layer of a magnetic
      material or linked to a (superpara, or ferro) MNP. The second approach involves
      doping of paramagnetic ions into QDs. A third option is to use silica or polymer
      nanoparticles as a matrix for the incorporation of both QDs and MNPs. Finally, it
      is possible to introduce chelating molecules with paramagnetic ions (e.g., Gd
      DTPA) into the coordination shell of the QDs. All different approaches have
      resulted in recent breakthroughs and the demonstration of the capability of
      bioimaging using both functionalities. In addition to giving an overview of the
      most exciting recent developments, the pros and cons of the four different
      classes of bimodal contrast agents are discussed, ending with an outlook on the
      future of this emerging new field.

PMID- 20049813
TI  - Methotrexate delivery via folate targeted dendrimer-based nanotherapeutic
      platform.
AB  - This paper provides a synopsis of the advancements made in advancing a dendrimer
      based nanomedicine towards human clinical trials by the Michigan Nanotechnology
      Institute for Medicine and Biological Sciences. A brief description of the
      synthesis and characterization of a targeted multifunctional therapeutic will
      demonstrate the simple yet delicate task of producing novel chemotherapeutic
      agents. The results obtained from in vitro and in vivo studies not only
      authenticate the potential of using nanoparticles to target therapeutics but also
      provide valuable insight towards the future directions of this technology. A
      fundamental, cross-disciplinary collaboration was necessary to achieve the
      synthesis and testing of this technology, and was the keystone to establishing
      this innovative invention. Throughout this paper, we will stress that the unique
      collaboration that facilitated the evolution of this technology is vital to the
      success of future developments in nanomedicine.

PMID- 20049815
TI  - ATP-loaded liposomes for treatment of myocardial ischemia.
AB  - A major obstacle to drug therapy for treatment of potential myocardial infarction
      is the limited access to the ischemic myocardium by drugs in an active form.
      Encouraging results have been reported with liposomes loaded with ATP in a
      variety of in vitro and in vivo models. We describe methods for optimized
      encapsulation of ATP in liposomes, enhancement of their effectiveness by
      increasing circulation time, and targeting of injured myocardial cells with
      surface attached antimyosin. In isolated ischemic rat hearts, ATP-loaded
      liposomes and ATP-loaded immunoliposomes effectively protected myocardium from
      ischemia/reperfusion damage as measured by systolic and diastolic functional
      improvements. In vivo, in rabbits with induced localized myocardial ischemia,
      liposomal encapsulation of ATP significantly diminished the proportion of
      ventricular muscle at risk that was irreversibly damaged during reperfusion.
      Therefore, ATP encapsulated in liposomes can provide an effective exogenous
      source for in vivo application which can protect ischemically damaged hearts.

PMID- 20049816
TI  - Nanotechnology in joint replacement.
AB  - This paper reviews the most relevant achievements and new developments in the
      field of nanomaterials and their possible impact on the fabrication of a new
      generation of reliable and longer lasting implants for joint replacement. Special
      emphasis is given to the role of nanocomposites with different microstructural
      designs: micro-nano composites, nano-nano composites, macro-micro-nano composites
      as well as bioinspired hierarchical composite materials. These nanostructured
      materials have opened up an exciting avenue in the design of non-metallic
      biocompatible, crack growth resistant, tough, and mechanically resistant implants
      with a lifespan close to the life expectancy of the patients.

PMID- 20049814
TI  - Biopersistence and potential adverse health impacts of fibrous nanomaterials:
      what have we learned from asbestos?
AB  - Human diseases associated with exposure to asbestos fibers include pleural
      fibrosis and plaques, pulmonary fibrosis (asbestosis), lung cancer, and diffuse
      malignant mesothelioma. The critical determinants of fiber bioactivity and
      toxicity include not only fiber dimensions, but also shape, surface reactivity,
      crystallinity, chemical composition, and presence of transition metals. Depending
      on their size and dimensions, inhaled fibers can penetrate the respiratory tract
      to the distal airways and into the alveolar spaces. Fibers can be cleared by
      several mechanisms, including the mucociliary escalator, engulfment, and removal
      by macrophages, or through splitting and chemical modification. Biopersistence of
      long asbestos fibers can lead to inflammation, granuloma formation, fibrosis, and
      cancer. Exposure to synthetic carbon nanomaterials, including carbon nanofibers
      and carbon nanotubes (CNTs), is considered a potential health hazard because of
      their physical similarities with asbestos fibers. Respiratory exposure to CNTs
      can produce an inflammatory response, diffuse interstitial fibrosis, and
      formation of fibrotic granulomas similar to that observed in asbestos-exposed
      animals and humans. Given the known cytotoxic and carcinogenic properties of
      asbestos fibers, toxicity of fibrous nanomaterials is a topic of intense study.
      The mechanisms of nanomaterial toxicity remain to be fully elucidated, but recent
      evidence suggests points of similarity with asbestos fibers, including a role for
      generation of reactive oxygen species, oxidative stress, and genotoxicity.
      Considering the rapid increase in production and use of fibrous nanomaterials, it
      is imperative to gain a thorough understanding of their biologic activity to
      avoid the human health catastrophe that has resulted from widespread use of
      asbestos fibers.

PMID- 20049817
TI  - Nanobiosystems.
AB  - 'Nanobiosystems' is a relatively new term describing objects in the size range
      below 150 nm and having structures or functions that link to biological
      functions. Key features are that these nanosized objects typically self-assemble,
      are not capable of self-replication, and have functions that take advantage of
      its size. Nanobiosystems can be made entirely of biological or organic molecules
      that are organized into nanoparticles (e.g., liposomes, dendrimers) or be totally
      inorganic (with the exception of surface coatings used for biocompatibility)
      nanoparticles (e.g., gold, iron oxide, quantum dot nanocrystals). More complex
      nanobiosystems are inorganic/biologic hybrid composites that may include complex
      multilayered structures with targeting molecules (e.g., peptides, antibodies,
      aptamers), cell entry-promoting molecules (e.g., HIV-tat peptide sequence), drugs
      (small molecules), genes (therapeutic genes, reporter genes), and core
      nanomaterials (e.g., gold, quantum dot, iron oxide) that give the nanobiosystems
      sometimes unique detection capabilities by a variety of optical and non-optical
      modalities (fluorescence, surface plasmon resonance, magnetic resonance imaging).

PMID- 20049818
TI  - Nanoporous membranes for medical and biological applications.
AB  - Synthetic nanoporous materials have numerous potential biological and medical
      applications that involve sorting, sensing, isolating, and releasing biological
      molecules. Nanoporous systems engineered to mimic natural filtration systems are
      actively being developed for use in smart implantable drug delivery systems,
      bioartificial organs, and other novel nano-enabled medical devices. Recent
      advances in nanoscience have made it possible to precisely control the morphology
      as well as physical and chemical properties of the pores in nanoporous materials
      that make them increasingly attractive for regulating and sensing transport at
      the molecular level. In this work, an overview of nanoporous membranes for
      biomedical applications is given. Various in vivo and in vitro membrane
      applications, including biosensing, biosorting, immunoisolation, and drug
      delivery, are presented. Different types of nanoporous materials and their
      fabrication techniques are discussed with an emphasis on membranes with ordered
      pores. Desirable properties of membranes used in implantable devices, including
      biocompatibility and antibiofouling behavior, are discussed. The use of surface
      modification techniques to improve the function of nanoporous membranes is
      reviewed. Despite the extensive research carried out in fabrication,
      characterization, and modeling of nanoporous materials, there are still several
      challenges that must be overcome in order to create synthetic nanoporous systems
      that behave similarly to their biological counterparts.

PMID- 20049819
TI  - Monodisperse magnetic nanoparticles for biodetection, imaging, and drug delivery:
      a versatile and evolving technology.
AB  - Advances in nanotechnology have pushed forward the synthesis of a variety of
      functional nanoparticles (NPs) such as semiconductor quantum dots (QDs), magnetic
      and metallic NPs. The unique electronic, magnetic, and optical properties
      exhibited by these nanometer-sized materials have enabled a broad spectrum of
      biomedical applications. In particular, iron-oxide-based magnetic NPs have proved
      to be highly versatile deep-tissue imaging agents, having been incorporated into
      clinical applications due to their biocompatibility. This Interdisciplinary
      Review will focus on the recent advances in strategies for the synthesis and
      surface modification of highly monodisperse magnetic NPs and their use in
      imaging, drug delivery, and innovative ultrasensitive bioassays.

PMID- 20049820
TI  - Nanoparticles in sentinel lymph node mapping.
AB  - The lymph nodes and lymphatic vessels are more difficult to access than most
      vascular structures. Interstitial injection of imaging agents is often necessary
      to opacify the lymphatics. Traditionally, radionuclide methods of sentinel node
      imaging have dominated this field, however, limitations in resolution and
      exposure to radiation have encouraged the development of newer imaging methods.
      Among these are magnetic resonance lymphography in which a Gadolinium labeled
      nanoparticle is injected and imaged providing superior anatomic resolution and
      assessment of lymphatic dynamics. Optical imaging employing various nanoparticles
      including quantum dots also provide the capability of mapping each lymphatic
      basin in another "color". Taken together this "toolbox" of lymphatic imaging
      agents is poised to improve our understanding of the lymphatic system.

PMID- 20049821
TI  - Atomic force microscopy and indentation force measurement of bone.
AB  - This review is summarizing the results obtained from atomic force microscopy
      (AFM) and nanoindentation experiments to date. The combination of both techniques
      is especially powerful. It allows to carefully choose indentation locations as
      well as the post-hoc analysis of the created indents, and hence the possibility
      to assess the properties of microstructural elements of bonessue. In addition,
      AFM has improved our understanding of bone ultrastructure and force spectroscopy
      experiments have led to the discovery of a molecular self-healing effect of bone
      that may be based on a small fraction of unstructured proteins. Nanoindentation
      measurements on bone, pose inherent problems since bone is an anisotropic solid
      showing elastic, viscoelastic, and time-dependent plastic behavior. Hence,
      derived parameters such as elastic modulus and hardness are to some extent
      dependent on measurement protocols. However, the development of extensions to the
      Oliver-Pharr method, being the most widely used analysis method, as well as novel
      dynamic testing techniques could improve the situation. Nanoindentation is widely
      used to study bone tissue and some important principal findings have been
      reported to date. These are presented here together with specific results from
      nanoindentation experiments of human and animal bones and tables are presented
      collating the data that can be found in the literature to date.

PMID- 20049822
TI  - Complex mathematical models of biology at the nanoscale.
AB  - Mathematical modeling of nanobiosystems is an exciting and rapidly growing new
      field of research that offers the potential to guide and improve technological
      developments in both nanomedicine and nanobiomaterial science. Unlike the more
      traditional fields of science and engineering, however, models of nanobiosystems
      are notoriously complex. In this paper, we highlight some of the primary sources
      of complexity in nanobiosystems. In particular, we focus on complexity that
      arises from the inherent nonlinearity of natural systems, noise generated by low
      copy numbers of relevant biological constituents, heterogeneity that stems from
      structure in physical systems at the nanoscale, strong coupling between processes
      that occur at different scales, and the large dimensions necessary to represent
      typical biological systems. We then suggest how different mathematical modeling
      techniques are currently being explored and developed to deal with the
      complicated and computationally demanding problems that can arise when modeling
      nanobiosystems. Although a relatively new field, mathematical descriptions of
      nanobiology are becoming increasingly more common and more important for both
      directing and interpreting experimental studies on nanobiosystems. The goal of
      this review is to emphasize the challenges associated with modeling
      nanobiosystems to inspire renewed effort in this highly interdisciplinary, but
      certainly rewarding, field.

PMID- 20049823
TI  - Characterization of nanomaterials for toxicity assessment.
AB  - A key element of any nanomaterial toxicity screening strategy is a detailed and
      comprehensive physicochemical characterization of the test material being
      studied. This is a critical factor for correlating the nanoparticle surface
      characteristics with any measured biological/toxicological responses, as well as
      to provide an adequate reference point for comparing toxicity results with the
      hazard-based findings of other investigators. Moreover, when hazard or risk-based
      evaluations are made on a particular nanomaterial (based on a variety of
      studies), it is important to ensure that the nanoparticle-types are identical or
      very similar in composition. This can only be accomplished if rigorous
      characterization is conducted. In the absence of an adequate assessment of the
      physical characteristics, it is easy to draw general conclusions on nanoparticle
      types which may have similar chemical compositions but, in fact, have different
      sizes, shapes, crystal structures, surface coatings, and surface reactivity
      characteristics. The determination of nanomaterial physicochemical properties is
      vitally important to nanomedicinal applications in that the fate, accumulation,
      and transport of nanomaterials through the body over time may be predicted based
      on specific surface characteristics.

PMID- 20049824
TI  - Transplacental transport of nanomaterials.
AB  - The unique properties of nanoparticles (NP) are key to the excitement over their
      potential application to benefit many aspects of our lives, but are also the
      cause of concern over inadequate toxicological assessment of their possible
      impact on human health. Nanotechnology is a rapidly expanding area of industrial
      activity in which NP are being developed for a wide range of purposes. With some
      of these products already in use, and many more soon to follow, it is critically
      important that the potential risks from this new technology are properly
      assessed. There is a pressing need to understand how engineered NP can interact
      with the human body following exposure as consumers, in the workplace or from the
      environment and fundamental to this is the assessment of NP interactions at
      biological barriers, which control access to the whole organism and specific
      organs. The placenta is a barrier of particular interest because it determines
      exposure of the foetus that represents a vulnerable and sensitive subpopulation
      requiring additional consideration. Little is currently known about whether NP
      can cross the human placental barrier or interfere with placental function but
      suitable transport models have been developed which can be used to clarify the
      mechanisms of cellular interaction and transport across the placenta.

PMID- 20049826
TI  - Carbon nanotubes towards medicinal biochips.
AB  - This overview focuses on the recent advances in carbon nanotube (CNT)-based
      biochips and tries to clarify their potential for modern molecular medicine.

PMID- 20049827
TI  - Molecular beacons and related probes for intracellular RNA imaging.
AB  - Accurately imaging endogenous or non-engineered RNA in live cells is not an easy
      task. Ideally, a probe and imaging strategy will have the following properties:
      (1) functional probes will be delivered to the desired cellular compartment, (2)
      they will achieve the correct level of affinity to bind target RNA efficiently
      but not inhibit their function, (3) be sensitive enough to allow for the accurate
      detection of the cellular RNA population, and (4) allow for the tracking of RNA
      through biogenesis, transport, translation, and degradation pathways. In this
      review, the capabilities of current nucleic acid-based probes and strategies used
      to image native RNA are discussed and analyzed, and probe and strategy
      recommendations for new users are given. The review is concluded by addressing
      topics for future research, all in the hope of achieving the ideal RNA imaging
      probe and strategy.

PMID- 20049828
TI  - Nanotechnology in the design of soft tissue scaffolds: innovations in structure
      and function.
AB  - Engineered scaffolds function to supplement or replace injured, missing, or
      compromised tissue or organs. The current direction in this research area is to
      create scaffolds that mimic the structure and function of the native
      extracellular matrix (ECM). It is believed that the fabrication of a scaffold
      that has both structural integrity and allows for normal cellular function and
      interaction will bring scaffolds closer to clinical relevance. Nanotechnology
      innovations have aided in the development of techniques for the production of
      nanofiber scaffolds. The three major processing techniques, self-assembly, phase
      separation, and electrospinning, produce fibers that rival the size of those
      found in the native ECM. However, the simplicity, versatility, and scalability of
      electrospinning make it an attractive processing method that can be used to
      reproduce aspects of the complexity that characterizes the native ECM. Novel
      electrospinning strategies include alterations of scaffold composition and
      architecture, along with the addition and encapsulation of cells, pharmaceuticals
      and growth factors within the scaffold. This article reviews the major nanofiber
      fabrication technologies as well as delves into recent significant contributions
      to the conception of a meaningful and practical electrospun scaffold.

PMID- 20049829
TI  - Quinoline-n-butylcyanoacrylate-based nanoparticles for brain targeting for the
      diagnosis of Alzheimer's disease.
AB  - A survey of research activity on nanoparticles (NPs) based on polymeric devices
      that could cross the blood-brain barrier (BBB) is given along with the
      presentation of our own data on the development of NPs of n-butyl-2-cyanoacrylate
      (BCA) for brain delivery to aid the early diagnosis of Alzheimer's disease (AD),
      a neurodegenerative disorder of the elderly people, the most prevalent form of
      dementia. Typical data are presented on in vivo detection of amyloid peptides (A
      beta) (amyloid plaques) that are used as targets for developing the biological
      markers for the diagnosis of AD. In order to develop efficient in vivo probes,
      polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated
      with the radio-labeled amyloid affinity drug (125)I-clioquinol (CQ, 5-chloro-7
      iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque
      retention of (125)I-CQ using the NPs of PBCA. The (125)I-CQ discriminately binds
      to the AD post-mortem brain tissue homogenates versus control. (125)I-CQ-PBCA NPs
      labeled the A beta plaques from the AD human post-mortem frontal cortical
      sections on paraffin-fixed slides. Storage phosphor imaging verified preferential
      uptake by AD brain sections compared to cortical control sections. The (125)I-CQ
      PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake
      measured in terms of % ID/g i.e., injected dose compared to (125)I-CQ. Brain
      retention of (125)I-CQ-PBCA NPs was significantly increased in the AD transgenic
      mice (APP/PS1) and in mice injected with aggregated A beta 42 peptide versus age
      matched wild type controls. The results of this study are verified by in vivo
      storage phosphor imaging and validated by histopathological staining of plaques
      and select metal ions, viz. Fe(2+) and Cu(2+). The (125)I-CQ-PBCA NPs had more
      efficient brain entry and rapid clearance in normal mice and enhanced the
      retention in AD mouse brain demonstrating the ideal in vivo imaging
      characteristics. The (125)I-CQ-PBCA NPs exhibited specificity for A beta plaques
      both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs
      as the promising delivery vehicle for in vivo single photon emission tomography
      (SPECT) ((123)I) or PET ((124)I) amyloid imaging agent. The importance of the
      topic in relation to brain delivery and other similar type of work published in
      this area are covered to highlight the importance of this research to medical
      disciplines.

PMID- 20049830
TI  - Probing dynamic fluorescence properties of single and clustered quantum dots
      toward quantitative biomedical imaging of cells.
AB  - We present results on the dynamic fluorescence properties of bioconjugated
      nanocrystals or quantum dots (QDs) in different chemical and physical
      environments. A variety of QD samples was prepared and compared: isolated
      individual QDs, QD aggregates, and QDs conjugated to other nanoscale materials,
      such as single-wall carbon nanotubes (SWCNTs) and human erythrocyte plasma
      membrane proteins. We discuss plausible scenarios to explain the results obtained
      for the fluorescence characteristics of QDs in these samples, especially for the
      excitation time-dependent fluorescence emission from clustered QDs. We also
      qualitatively demonstrate enhanced fluorescence emission signals from clustered
      QDs and deduce that the band 3 membrane proteins in erythrocytes are clustered.
      This approach is promising for the development of QD-based quantitative molecular
      imaging techniques for biomedical studies involving biomolecule clustering.

PMID- 20049831
TI  - Nanogenomics in medicine.
AB  - This review presents the status of technological developments of nanogenomics and
      its applications to medicine. Even if particular emphasis is placed on what has
      been accomplished in our laboratory in the last few years in the area of genes
      microarrays, significant reference to the recent activity of numerous other
      groups can be found in Refs 1,2.

PMID- 20049832
TI  - Heparin-based nanoparticles.
AB  - The combination of nanoparticles and biological molecules is of intense interest
      because of the synergistic properties offered by such newly synthesized
      composites. Heparin (HP), conjugated to nanomaterials, has recently been
      investigated for its chemical and biological properties. HP has a number of
      biological activities that can be enhanced when composited with nanoparticles. In
      addition, HP improves the biocompatibility of nanoparticles improving their
      performance in various biological applications. A variety of recent research
      combines HP and nanomaterials for a myriad of applications. HP has been
      conjugated to the surface of the nanoparticles, such as magnetic and metallic
      nanoparticles, or biodegradable and nondegradable synthetic polymers. HP has also
      been incorporated into the nanoparticles. There are numerous possibilities for
      material composites and chemistries that incorporate HP. This opens the door for
      novel applications ranging from improving anticoagulant activity, for anticancer
      and antitumor therapy, to tissue engineering and biosensors. This review examines
      the different possibilities of HP-based nanoparticle composites and their
      medicinal or biological applications.

PMID- 20049833
TI  - Maximizing safe design of engineered nanomaterials: the NIH and NIEHS research
      perspective.
AB  - Estimating potential risk of an emerging technology as its products are being
      developed offers the greatest potential for success of the technology. The
      National Nanotechnology Initiative was launched in 2000 to provide a federal
      framework to support safe and responsible development of nanotechnology.Within
      this framework, the National Institutes of Health (NIH) focuses resources and
      expertise on both the biomedical applications of nanotechnology and the
      possibility of adverse health effects, or implications research. NIH developed
      the NanoHealth and Safety Enterprise Initiative by identifying shared research
      needs across the nanotechnology applications and implications research
      communities to create an integrated research strategy to maximize resources and
      expedite the development of engineered nanomaterials (ENM) that are safe by
      design. The central goal of this program is to decipher the fundamental
      principles of ENM interactions with biological systems that are relevant to human
      exposure and physiological response. Program components include materials
      science, basic biology, pathobiology, and informatics, as well as a cross
      disciplinary training program for new nanotechnology scientists. The magnitude of
      this program will be best supported by flexible, dynamic funding and research
      mechanisms including the formation of public-private partnerships that span the
      expertise and interests of government, industry, academia, public interest, and
      other stakeholders. It is through such innovative, integrated, and cross
      disciplinary programs that the full promise of nanotechnology may be realized
      while ensuring that this emerging field does not succumb to hidden perils.

PMID- 20049834
TI  - Nanomaterial standards for efficacy and toxicity assessment.
AB  - Decreased toxicity via selective delivery of cancer therapeutics to tumors has
      become a hallmark achievement of nanotechnology. In order to be optimally
      efficacious, a systemically administered nanomedicine must reach cancer cells in
      sufficient quantities to elicit a response and assume its active form within the
      tumor microenvironment (e.g., be taken up by cancer cells and release a toxic
      component once within the cytosol or nuclei). Most nanomedicines achieve
      selective tumor accumulation via the enhanced permeability and retention (EPR)
      effect or a combination of the EPR effect and active targeting to cellular
      receptors. Here, we review how the fundamental physicochemical properties of a
      nanomedicine (its size, charge, hydrophobicity, etc.) can dramatically affect its
      distribution to cancerous tissue, transport across vascular walls, and retention
      in tumors. We also discuss how nanoparticle characteristics such as stability in
      the blood and tumor, cleavability of covalently bound components, cancer cell
      uptake, and cytotoxicity contribute to efficacy once the nanoparticle has reached
      the tumor's interstitial space. We elaborate on how tumor vascularization and
      receptor expression vary depending on cancer type, stage of disease, site of
      implantation, and host species, and review studies which have demonstrated that
      these variations affect tumor response to nanomedicines. Finally, we show how
      knowledge of these properties (both of the nanoparticle and the cancer/tumor
      under study) can be used to design meaningful in vivo tests to evaluate
      nanoparticle efficacy.

PMID- 20049836
TI  - Changes in US antidepressant and antipsychotic prescription patterns during a
      period of FDA actions.
AB  - PURPOSE: To determine if paroxetine versus non-paroxetine selective serotonin
      reuptake inhibitors (SSRIs) prescribing changed after the June 2003 FDA
      Paroxetine Public Health Advisory (PPHA) and if antidepressant and antipsychotic
      prescribing changed after the February 2004 FDA Advisory Committee Meeting
      (FDACM). METHODS: Ecologic analysis using estimates of patients dispensed
      antidepressants and antipsychotics, census data, and promotional spending data.
      Data sources were SDI: Vector One(R), US Census, and IMS Health(R). Measures were
      monthly use levels (number of patients dispensed antidepressants, antipsychotics,
      paroxetine, and non-paroxetine SSRIs prescriptions by age group per population
      count). Percent changes pre- to post-PPHA were used to assess changes in
      paroxetine versus non-paroxetine SSRIs prescribing. Interrupted time series (ITS)
      analysis was performed to examine use level changes post-FDACM by drug groups
      (all antidepressants and all antipsychotics). RESULTS: Post-PPHA mean paroxetine
      use levels decreased for all age groups (range: 5.5-34.1%). Mean non-paroxetine
      SSRIs use levels increased (range: 4.6-17.1%). Post-PPHA changes were greatest
      for 6-12 and 13-17 year olds. Decreased mean antidepressant drug use levels from
      pre- to post-FDACM were observed in all groups under 25 years old. A
      statistically significant decrease in the slopes from pre- to post-FDACM was
      observed for persons aged 13-17 and 18-24 years. The difference between the
      forecasted mean use level and the observed mean use level (in 12-month intervals)
      was statistically significant for all ages combined (-107.26; 95% CI: -166.32, 
      48.20) and 1-5 (-3.1; 95% CI: -4.62, -1.58), 6-12 (-36.02; 95% CI: -62.92, -9.12)
      and 25 years, and older groups (-83.17; 95% CI: -153.95, -12.39). For all age
      groups, decreases in the slopes of antipsychotic drugs use from pre- to post
      FDACM were observed, although these slope changes were not statistically
      significant. The difference between the forecasted mean antipsychotic drugs use
      level and the observed mean use level (in 12-month intervals) was statistically
      significantly lower for all age groups. CONCLUSIONS: Antidepressant use changed
      post-PPHA and -FDACM, with a differential pattern by age. There was no evidence
      of increased antipsychotic use post-FDACM. Ecologic data cannot determine if
      changes were due to depression not treated with medications or the prescribing of
      fewer antidepressants for other conditions.

PMID- 20049835
TI  - Cancer incidence in people with AIDS in Italy.
AB  - People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction
      of highly active antiretroviral therapies (HAART) has improved their life
      expectancy, exposing them to the combined consequences of aging and of a
      prolonged exposure to cancer risk factors. The aim of this study was to estimate
      incidence rates (IR) in PWHA in Italy, before and after the introduction of
      HAART, after adjusting for sex and age through direct standardization. An
      anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer
      Registries (17.3 million, 30% of Italian population) was performed. In PWHA,
      crude IR, sex- and age-standardized IR and age-specific IR were estimated. The
      standardized IR for Kaposi sarcoma and non-Hodgkin lymphoma greatly declined in
      the HAART period. Although the crude IR for all non-AIDS-defining cancers
      increased in the HAART period, standardized IR did not significantly differ in
      the 2 periods (352 and 379/100,000, respectively). Increases were seen only for
      cancer of the liver (IR ratio = 4.6, 95% CI: 1.3-17.0) and lung (IR ratio = 1.8,
      95% CI: 1.0-3.2). Age-specific IRs for liver and lung cancers, however, largely
      overlapped in the 2 periods pointing to the strong influence of the shift in the
      age distribution of PWHA on the observed upward trends. In conclusion,
      standardized IRs for non-AIDS-defining cancers have not risen in the HAART
      period, even if crude IRs of these cancers increased. This scenario calls,
      however, for the intensification of cancer-prevention strategies, notably smoking
      cessation and screening programs, in middle-aged HIV-patients.

PMID- 20049837
TI  - Additional value of EGFR downstream signaling phosphoprotein expression to KRAS
      status for response to anti-EGFR antibodies in colorectal cancer.
AB  - KRAS mutations are a strong predictive marker of resistance to anti-epidermal
      growth factor receptor (EGFR) antibodies in advanced colorectal cancer (CRC) but
      only a subset of wild-type (WT) KRAS patients are responders, suggesting the
      existence of additional markers of resistance to this treatment. The activation
      of EGFR downstream signaling pathways may be one of these ones. In a series of 42
      patients with advanced CRC treated with cetuximab/panitumumab, for whom KRAS
      status was previously determined, we retrospectively analyzed the intratumor
      expression of EGFR downstream signaling phosphoproteins of the RAS/MAPK and
      PI3K/AKT pathways (pERK1/2, pMEK1, pAKT, pP70S6K and pGSK3beta) using Bio-Plex
      phosphoprotein array. Association with tumor response, progression-free survival
      (PFS) and overall survival (OS) was assessed. The expression of all the
      phosphoproteins was higher in KRAS mutated tumors than in WT tumors. The
      expression of pP70S6K was lower in responders than in nonresponder patients. In
      univariate analysis, patients with high pMEK1 or pP70S6K expression had a shorter
      PFS than those with low expression. Patients with high pP70S6K expression also
      had a shorter OS. In multivariate analysis, PFS was shorter for patients with
      high pMEK1 or pP70S6K expression, independently of KRAS status, as OS for
      patients with high pP70S6K expression. Therefore, WT KRAS patients with high
      pP70S6K expression had a shorter survival than those with low expression. Our
      results suggest the importance of EGFR downstream signaling phosphoproteins
      expression in addition to KRAS status to define the subgroup of patients who will
      not benefit from anti-EGFR therapy.

PMID- 20049838
TI  - Cost-effectiveness analysis of cervical cancer prevention based on a rapid human
      papillomavirus screening test in a high-risk region of China.
AB  - This study assessed the cost-effectiveness of a new, rapid human papillomavirus
      (HPV)-DNA screening test for cervical cancer prevention in the high-risk region
      of Shanxi, China. Using micro-costing methods, we estimated the resources needed
      to implement preventive strategies using cervical cytology or HPV-DNA testing,
      including the Hybrid Capture 2 (hc2) test (QIAGEN Corp., Gaithersburg, MD) and
      the rapid HPV-DNA careHPV test (QIAGEN). Data were used in a previously published
      model and empirically calibrated to country-specific epidemiological data.
      Strategies differed by initial test, targeted age, frequency of screening, number
      of clinic visits required (1, 2 or 3) and service delivery setting (national,
      county and township levels). Outcomes included lifetime risk of cancer, years of
      life saved (YLS), lifetime costs and incremental cost-effectiveness ratios (cost
      per YLS). For all screening frequencies, the most efficient strategy used 2-visit
      rapid HPV-DNA testing at the county level, including screening and diagnostics in
      the first visit, and treatment in the second visit. Screening at ages 35, 40 and
      45 reduced cancer risk by 50% among women compliant with all 3 screening rounds,
      and was US$ 150 per YLS, compared with this same strategy applied twice per
      lifetime. This would be considered very cost-effective evaluated against China's
      per-capita gross domestic product (US$ 1,702). By enhancing the linkage between
      screening and treatment through a reduced number of visits, rapid HPV-DNA testing
      3 times per lifetime is more effective than traditional cytology, and is likely
      to be cost-effective in high-risk regions of China.

PMID- 20049839
TI  - Allogeneic hematopoietic stem cell transplantation in ovarian cancer-the EBMT
      experience.
AB  - Although preliminary results suggest that allogeneic hematopoietic stem cell
      transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the
      low patient number in previous studies had limited ability to evaluate the true
      benefit of allo HCT in OC. This retrospective multicenter study included 30
      patients with OC allografted between 1995 and 2005 to determine the outcome of
      patients with OC treated with allo HCT. Prior to allo HCT, patients were in
      complete response (n = 1), partial response (n = 7), stable disease (n = 11) or
      had progressive disease (n = 13). An objective response (OR) was observed in 50%
      (95% CI, 33-67) of patients. Three patients of responding patients had an
      objective response following the development of acute graft-versus-host disease
      (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18
      50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year,
      respectively. With a median follow-up of 74.5 months (range 16-148), median
      progression free survival (PFS) was 6 months and median overall survival (OS) was
      10.4 months. Patients who developed cGvHD following allo HCT had a significant OS
      improvement compared to those who did not (17.6 months vs. 6.5 months, p =
      0.042). However, PFS was not similarly significantly improved in patients who
      developed cGvHD (12 months versus 3.7 months, p = 0.81). Allo HCT in OC may lead
      to graft-versus-OC effects. Their clinical relevance remains to be shown.

PMID- 20049840
TI  - Inter-test agreement and quantitative cross-validation of immunochromatographical
      fecal occult blood tests.
AB  - Immunochromatographical fecal occult blood tests were shown to have higher
      sensitivity for detecting colorectal neoplasms than the commonly used guaiac
      based test. However, positivity rates, sensitivity and specificity vary widely.
      We aimed to assess the reasons for this heterogeneity. Six dichotomous
      (qualitative) immunochromatographical tests were used in the same stool samples,
      taken before cathartic bowel preparation, from 1,330 participants of the German
      colonoscopy screening program. Positivity rates were determined, and inter-test
      agreement beyond chance was quantified by kappa coefficients (kappa). In
      addition, kappa coefficients were expressed in relation to their maximum possible
      values given differences in test positivity rates (kappa/kappa(max)).
      Furthermore, the distribution of fecal hemoglobin concentration was assessed by
      an additional quantitative test in participants classified as clearly positive,
      borderline positive or clearly negative according to the qualitative tests.
      Positivity rates strongly varied from 6.4 to 46.8%. As a result, overall
      agreement between tests was only poor to moderate, with kappa ranging from 0.14
      to 0.61. However, apart from the different positivity rates, agreement was mostly
      very high, with kappa/kappa(max) ranging from 0.53 to 1.00, and exceeding 0.70 in
      12 of 15 cases. Distribution of fecal hemoglobin concentrations in the various
      categories strongly varied across tests. The observed patterns suggest that the
      strongly different positivity rates essentially reflect different cutoff levels
      of tests with otherwise very high inter-test agreement. Definition of cutoffs is
      a critical issue in the application of immunochromatographical tests and should
      be redefined for several of these tests.

PMID- 20049841
TI  - Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian
      carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration
      with downregulation of E-cadherin.
AB  - Histone acetylation/deacetylation controls chromatin activity and subsequent gene
      transcription. Recent studies demonstrated the activation of histone deacetylases
      (HDACs) in various human malignancies; however, the expression and function of
      HDACs in ovarian tumors are not fully understood. In this study, we examined the
      immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained
      from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth
      marker), p21, and E-cadherin and clinicopathological parameters. In addition, we
      analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the
      expression of cell cycle-related molecules and E-cadherin to clarify the
      functional difference among the 3 HDACs. The results indicated that the
      immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins
      increased stepwise in benign, borderline and malignant tumors. The expression of
      HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was
      inversely correlated with E-cadherin expression. Among the HDACs examined, only
      HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC
      inhibitors suppressed the proliferation of ovarian cancer cells in association
      with apoptosis. A specific siRNA for HDAC1 significantly reduced the
      proliferation of ovarian carcinoma cells via downregulation of cyclin A
      expression, but siRNA for HDAC3 reduced the cell migration with elevated E
      cadherin expression. Our results suggested that HDAC1 plays an important role in
      the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell
      adhesion and migration. Therefore, specific therapeutic approaches should be
      considered according to the HDAC subtypes.

PMID- 20049842
TI  - Family history of cancer and risk of pancreatic cancer: a pooled analysis from
      the Pancreatic Cancer Cohort Consortium (PanScan).
AB  - A family history of pancreatic cancer has consistently been associated with
      increased risk of pancreatic cancer. However, uncertainty remains about the
      strength of this association. Results from previous studies suggest a family
      history of select cancers (i.e., ovarian, breast and colorectal) could also be
      associated, although not as strongly, with increased risk of pancreatic cancer.
      We examined the association between a family history of 5 types of cancer
      (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic
      cancer using data from a collaborative nested case-control study conducted by the
      Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies
      from the United States, Europe and China, and a case-control study from the Mayo
      Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and
      1,205 controls. A family history of pancreatic cancer in a parent, sibling or
      child was associated with increased risk of pancreatic cancer [multivariate
      adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A
      family history of prostate cancer was also associated with increased risk (OR =
      1.45, 95% CI = 1.12-1.89). There were no statistically significant associations
      with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast
      cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI =
      0.93-1.47). Our results confirm a moderate sized association between a family
      history of pancreatic cancer and risk of pancreatic cancer and also provide
      evidence for an association with a family history of prostate cancer worth
      further study.

PMID- 20049843
TI  - Preference-based condition-specific measures of health: what happens to cross
      programme comparability?

PMID- 20049846
TI  - Src signaling in cancer invasion.
AB  - Src is a non-receptor cytoplasmic tyrosine kinase which becomes activated
      following the stimulation of plasma membrane receptors including receptor
      tyrosine kinases and integrins, and is an indispensable player of multiple
      physiological homeostatic pathways. Once activated, Src is the starting point for
      several biochemical cascades that thereby propagate signals generated
      extracellularly along intracellular interconnected transduction pathways. Src
      transmits signals promoting cell survival and mitogenesis and, in addition,
      exerts a profound effect on the reorganization of the cytoskeleton and the
      adhesion systems that underpin cell migration and invasion. Because increased
      activity of Src is a frequent occurrence in many types of human cancer, and
      because there is evidence of a prominent role of Src in invasion and in other
      tumor progression-related events such as epithelial-mesenchymal transition (EMT)
      and development of metastasis, inhibitors targeting Src are being viewed as
      promising drugs for cancer therapy.

PMID- 20049844
TI  - Binding site on human immunoglobulin G for the affinity ligand HWRGWV.
AB  - Affinity ligand HWRGWV has demonstrated the ability to isolate human
      immunoglobulin G (hIgG) from mammalian cell culture media. The ligand
      specifically binds hIgG through its Fc portion. This work shows that
      deglycosylation of hIgG has no influence on its binding to the HWRGWV ligand and
      the ligand does not compete with Protein A or Protein G in binding hIgG. It is
      suggested by the mass spectrometry (MS) data and docking simulation that HWRGWV
      binds to the pFc portion of hIgG and interacts with the amino acids in the loop
      Ser383-Asn389 (SNGQPEN) located in the C(H)3 domain. Subsequent modeling has
      suggested a possible three-dimensional minimized solution structure for the
      interaction of hIgG and the HWRGWV ligand. The results support the fact that a
      peptide as small as a hexamer can have specific interactions with large proteins
      such as hIgG.

PMID- 20049847
TI  - Cell-fusion-mediated somatic-cell reprogramming: a mechanism for tissue
      regeneration.
AB  - Spontaneous cell fusion between two cells of different lineages will originate
      new hybrid cells that have different features from the original parent cells. It
      has been shown that injury to a tissue can enhance spontaneous cell-cell fusion
      events. If one of the parent cells of a cell-cell fusion is highly plastic, such
      as a stem cell, and the other is a somatic cell, their fusion can be followed by
      reprogramming events that can generate new hybrid pluripotent cells. These, in
      turn, have the potential to differentiate and regenerate the damaged tissue.
      However, if this process is deregulated, this would provide a mechanism for
      cancer development.

PMID- 20049848
TI  - Resolving a genetic paradox throughout preimplantation genetic diagnosis for
      autosomal dominant severe congenital neutropenia.
AB  - OBJECTIVE: Severe congenital neutropenia is an inherited disease characterized by
      low peripheral blood neutrophils, amenable to bone marrow transplantation.
      Genetic analysis in the family here described detected a ELA2 splice-site
      mutation in the affected child and also in his asymptomatic father. The parents
      requested preimplantation genetic diagnosis (PGD), coupled with HLA matching, to
      obtain a suitable bone marrow donor for the affected child. METHODS: A PGD
      protocol was developed, based on multiplex nested PCR for direct analysis of the
      ELA2 mutation, flanking polymorphic markers and HLA typing. RESULTS: The
      amplification efficiency of the mutation was > 90% in single leukocytes from the
      affected child but only 67% in the father. Analysis of single haploid sperm cells
      from the father demonstrated three different sperm-cell populations: (1) sperm
      cells harboring the ELA2 mutation on the 'affected' haplotype, (2) sperm cells
      without the ELA2 mutation on the 'normal' haplotype, and (3) sperm cells without
      the ELA2 mutation on the 'affected' haplotype. CONCLUSION: These data demonstrate
      that the ELA2 mutation in the father occurred de novo during his embryonic
      development, resulting in somatic as well as germ-line mosaicism. This conclusion
      was also taken into consideration when PGD was performed.

PMID- 20049849
TI  - Potential bias caused by control selection in secondary data analysis: nonaspirin
      nonsteroidal anti-inflammatory drugs and hemorrhagic stroke.
AB  - BACKGROUND: This study investigated the potential for bias introduction when
      selecting controls for secondary analysis of case-control study data. METHODS: We
      used a data set previously collected for an acute brain bleeding analysis (ABBA)
      study, which was designed to investigate the risk of hemorrhagic stroke (HS)
      resulting from the use of phenylpropanolamine in Korea. Cases in that study had
      experienced an HS. Each HS case was matched with age- and gender-based hospital
      and community controls. Information was obtained on drug exposures including
      nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs). Odds ratios (OR) for,
      and 95% confidence intervals (CI) of, experiencing an HS were calculated using
      conditional logistic regressions for each control group. RESULTS: A total of 940
      patients were matched with 1880 controls. The OR of HS occurring in NANSAID users
      was 1.18 (95%CI, 0.80-1.73) in community controls and 0.67 (95%CI, 0.45-0.98) in
      hospital controls. The majority of the hospital controls were selected from
      patients who had visited neurology, neurosurgery, or orthopedic departments.
      CONCLUSION: The difference between OR values estimated from hospital and
      community controls could be the result of selection bias. The study data were
      originally obtained for a different purpose than this study, and NANSAID use was
      not considered when the hospital controls were selected. When performing
      secondary analyses, extra care is needed to note whether the results are
      consistent across control groups and whether there are indications of bias
      related to the selection of those controls.

PMID- 20049850
TI  - Prenatal diagnosis of del(4)(q27q31.23), due to a maternal balanced complex
      chromosome rearrangement, characterized by array-CGH.

PMID- 20049851
TI  - Signal detection of rosuvastatin compared to other statins: data-mining study
      using national health insurance claims database.
AB  - PURPOSE: To detect adverse drug reaction (ADR) signals of rosuvastatin compared
      to other statins with a novel data-mining approach based on relative risk (RR)
      using the national health insurance claims database, and to evaluate the
      usefulness of this method as a tool for signal detection. METHODS: We used the
      Health Insurance Review & Assessment Service (HIRA) claims database (Seoul,
      Korea). Serious adverse events (SAE) were defined as any diagnostic code at the
      time of hospitalization within 12 weeks from a statin prescription date,
      regardless of causality. Among statin users, RRs were calculated to compare the
      proportion of rosuvastatin-specific SAE pairs for rosuvastatin users with the
      corresponding proportion of drug-SAE pairs for users of other statins. Any SAE
      for which the lower limit of the RR's 95% confidence interval was greater than 1
      was defined as a signal. All detected signals were reviewed to determine whether
      the signals corresponded with published adverse events (AEs) exclusive to
      rosuvastatin. RESULTS: Among 96 236 elderly outpatients who received
      rosuvastatin, or other statins, from January 2005 to September 2005, 40 304 drug
      SAE pairs and 376 SAEs were observed. Twenty-five (6.6%) SAEs were detected as
      signals by the RR-based data-mining approach. Among the 13 references AEs
      published to be exclusive to rosuvastatin, 8 (61.5%) were found to correspond
      with the detected signals with a positive predictive value (PPV) of 32%.
      CONCLUSIONS: The RR-based data-mining approach successfully detected signals for
      rosuvastatin using a national health insurance claims database. This approach
      could be useful for safety surveillance of marketed products.

PMID- 20049852
TI  - Impact of growth factors and PTHrP on early and late chondrogenic differentiation
      of human mesenchymal stem cells.
AB  - Common in vitro protocols for chondrogenesis of mesenchymal stem cells (MSCs)
      induce an inadequate, hypertrophic differentiation cascade reminiscent of
      endochondral bone formation. We aimed to modify chondrogenic protocols in order
      to identify potent inducers, promotors, and inhibitors to achieve better
      chondrogenesis. Nine factors suspected to stimulate or inhibit chondrogenesis
      were used for chondrogenic in vitro induction of MSC. Differentiation was
      assessed by immunohistochemistry, alcian-blue staining, qRT-PCR, and
      quantification of alkaline phosphatase (ALP) activity. Pre-differentiated pellets
      were transplanted subcutaneously into SCID mice to investigate stable cartilage
      formation. Transforming growth factor (TGF)-beta was always required for
      chondrogenic differentiation and deposition of a collagen-type-II-positive
      extracellular matrix, while bone morphogenetic protein (BMP)-2, -4, -6, -7, aFGF,
      and IGF-I (10 ng/ml) were alone not sufficiently inductive. Each of these factors
      allowed differentiation in combination with TGF-beta, however, without preventing
      collagen type X expression. bFGF or parathyroid hormone-like peptide (PTHrP)
      inhibited the TGF-beta-responsive COL2A1 and COL10A1 expression and ALP induction
      when added from day 0 or 21. In line with a reversible ALP inhibition, in vivo
      calcification of pellets was not prevented. Late up-regulation of PTH1R mRNA
      suggests that early PTHrP effects may be mediated by a receptor-independent
      pathway. While TGF-beta was a full inducer, bFGF and PTHrP were potent inhibitors
      for early and late chondrogenesis, seemed to induce a shift from matrix anabolism
      to catabolism, but did not selectively suppress COL10A1 expression. Within a
      developmental window of collagen type II(+)/collagen type X(-) cells, bFGF and
      PTHrP may allow inhibition of further differentiation toward hypertrophy to
      obtain stable chondrocytes for transplantation purposes.

PMID- 20049853
TI  - Ion transport in a human lens epithelial cell line exposed to hyposmotic and
      apoptotic stress.
AB  - Membrane transport changes in human lens epithelial (HLE-B3) cells under
      hyposmotic and apoptotic stress were compared. Cell potassium content, K(i),
      uptake of the K congener rubidium, Rb(i), and water content were measured after
      hyposmotic stress induced by hypotonicity, and apoptotic stress by the protein
      kinase inhibitor staurosporine (STP). Cell water increased in hyposmotic (150
      mOsm) as compared to isosmotic (300 mOsm) balanced salt solution (BSS) by >2-fold
      at 5 min and decreased within 15 min to baseline values accompanied by a 40% K(i)
      loss commensurate with cell swelling and subsequent cell shrinkage likely due to
      regulatory volume decrease (RVD). Loss of K(i), and accompanying water, and Rb(i)
      uptake in hyposmotic BSS were prevented by clotrimazole (CTZ) suggesting water
      shifts associated with K and Rb flux via intermediate conductance K (IK)
      channels, also detected at the mRNA and protein level. In contrast, 2 h after 2
      microM STP exposure, the cells lost approximately 40% water and approximately 60%
      K(i), respectively, consistent with apoptotic volume decrease (AVD). Indeed,
      water and K(i) loss was at least fivefold greater after hyposmotic than after
      apoptotic stress. High extracellular K and 2 mM 4-aminopyridine (4-AP) but not
      CTZ significantly reduced apoptosis. Annexin labeling phosphatidylserine (PS) at
      15 min suggested loss of lipid asymmetry. Quantitative PCR revealed significant
      IK channel expression during prolonged hyposmotic stress. Results suggest in HLE
      B3 cells, IK channels likely partook in and were down regulated after RVD,
      whereas pro-apoptotic STP-activation of 4-AP-sensitive voltage-gated K channels
      preceded or accompanied PS externalization before subsequent apoptosis.

PMID- 20049854
TI  - Cyclophilin C-associated protein/Mac-2 binding protein colocalizes with calnexin
      and regulates the expression of tissue transglutaminase.
AB  - Cyclophilin C-associated protein (CyCAP) or Mac-2 binding protein has been
      identified as a binding protein for cyclophilin C in mice and for Mac-2 (galectin
      3) in human, suggesting its multiple binding activity to proteins. In the present
      study, using specific anti-rat-CyCAP antibody, we found that CyCAP colocalizes
      with calnexin at the location near the nuclear envelope, however CyCAP does not
      have colocalization with calreticulin. In senescent fibroblasts and interferon
      gamma (IFNgamma) treated fibroblasts, both calnexin and CyCAP form larger
      polymers and are released from the endoplasmic reticulum (ER) through the
      cellular membrane to the extracellular area. Immunoprecipitation studies further
      confirm that the release of calnexin is through binding to CyCAP. Further, we
      found that tissue transglutaminase (tTG) protein is decreased, however not at the
      RNA level, in CyCAP null fibroblasts, which suggests that CyCAP is involved in
      tTG post-translational modification. Our data give novel evidence that CyCAP
      regulates the post-translational modification of tTG through its colocalization
      with calnexin in ER.

PMID- 20049855
TI  - Differential proteomic analysis reveals novel links between primary metabolism
      and antibiotic production in Amycolatopsis balhimycina.
AB  - A differential proteomic analysis, based on 2-DE and MS procedures, was performed
      on Amycolatopsis balhimycina DSM5908, the actinomycete producing the vancomycin
      like antibiotic balhimycin. A comparison of proteomic profiles before and during
      balhimycin production characterized differentially and constitutively expressed
      protein isoforms, which were associated with 203 ORFs in the A. balhimycina
      genome. These data, providing insights on the major metabolic pathways/molecular
      processes operating in this organism, were used to compile 2-DE reference maps
      covering 3-10, 4-7 and 4.5-5.5 pH gradients available over the World Wide Web as
      interactive web pages (http://www.unipa.it/ampuglia/Abal-proteome-maps).
      Functional clustering analysis revealed that differentially expressed proteins
      belong to functional groups involved in central carbon metabolism, amino acid
      metabolism and protein biosynthesis, energetic and redox balance, sugar/amino
      sugar metabolism, balhimycin biosynthesis and transcriptional regulation or with
      hypothetical and/or unknown function. Interestingly, proteins involved in the
      biosynthesis of balhimycin precursors, such as amino acids, amino sugars and
      central carbon metabolism intermediates, were upregulated during antibiotic
      production. qRT-PCR analysis revealed that 8 out of 14 upregulated genes showed a
      positive correlation between changes at translational and transcriptional
      expression level. Furthermore, proteomic analysis of two nonproducing mutants,
      restricted to a sub-set of differentially expressed proteins, showed that most
      proteins required for the biosynthesis of balhimycin precursors are downregulated
      in both mutants. These findings suggest that primary metabolic pathways support
      anabolic routes leading to balhimycin biosynthesis and the differentially
      expressed genes are interesting targets for the construction of high-yielding
      producer strains by rational genetic engineering.

PMID- 20049856
TI  - Functional proteomic and structural insights into molecular targets related to
      the growth inhibitory effect of tanshinone IIA on HeLa cells.
AB  - Certain antitumor agents have recently been extracted from the roots of Salvia
      miltiorrhiza Bunge. The diterpene derivative, tanshinone IIA, possesses cytotoxic
      activity against several human carcinoma cell lines. It also inhibits invasion
      and metastasis of cancer cells. In the present study, we isolated tanshinone IIA
      from S. miltiorrhiza, and it exhibited strong growth inhibition against human
      cervical cancer cells in dose- and time-dependent manners with a 50% cell growth
      inhibition value of 2.5 microg/mL (8.49 microM). Flow cytometric analysis of cell
      cycle progression revealed that G(2)/M arrest was initiated after a 24 h exposure
      to the drug. It also resulted in DNA fragmentation and degradation of poly (ADP
      ribose) polymerase indicating that tanshinone IIA may be a potential antitumor
      agent. Furthermore, we performed a comprehensive proteomic analysis to survey
      global protein changes induced by tanshinone IIA treatment on HeLa cells.
      Significant changes in the levels of cytoskeleton proteins as well as stress
      associated proteins were observed. Immunoblot analysis and immunofluorescence
      staining were used to confirm the levels of protein expression. Overexpression of
      the vimentin rescued these tanshinone IIA-induced events. Computational docking
      methods indicated that tanshinone IIA could stably bind to the beta-subunit of
      the microtubule protein. An interaction network analysis of these 12 proteins
      using MetaCore software suggested that tanshinone IIA treatment regulated the
      expressions of proteins involved in apoptotic processes, spindle assembly, and
      p53 activation, including vimentin, Maspin, alpha- and beta-tubulin, and GRP75.
      Taken together, our results suggest that tanshinone IIA strongly inhibited the
      growth of cervical cancer cells through interfering in the process of microtubule
      assembly, leading to G(2)/M phase arrest and sequent apoptosis. The success of
      this large-scale effort was assessed by a bioinformatics analysis of proteins
      through predictions of protein domains and possible functional roles. The
      possible contributions of these proteins to the cytotoxicity of tanshinone IIA
      provide potential opportunities for the development of cancer therapeutics.

PMID- 20049857
TI  - Screening of Ole e 1 polymorphism among olive cultivars by peptide mapping and N
      glycopeptide analysis.
AB  - In the present paper, we have used 2-DE coupled to MS analysis to examine the
      molecular variability of the Ole e 1 allergen in three olive cultivars (cvs). Our
      results confirmed that the predicted polymorphism of Ole e 1 at cDNA level is
      extended to the expressed protein. The profiles of both the Ole e 1 peptides and
      the N-glycan variants significantly changed among cvs. We observed that Picual
      and Arbequina cvs presented the highest and lowest degree of Ole e 1
      polymorphism, respectively. Some of these peptides and N-glycans were distributed
      in a cv-specific manner. The putative implications of this molecular polymorphism
      in the development of the allergy symptoms are discussed.

PMID- 20049858
TI  - Application of free-flow IEF to identify protein candidates changing under
      microgravity conditions.
AB  - Using antibody-related methods, we recently found that human thyroid cells
      express various proteins differently depending on whether they are cultured under
      normal gravity (1g) or simulated microgravity (s-microg). In this study, we
      performed proteome analysis in order to identify more gravity-sensitive thyroid
      proteins. Cells cultured under 1g or s-microg conditions were sonicated. Proteins
      released into the supernatant and those remaining in the cell fragments were
      fractionated by free-flow IEF. The fractions obtained were further separated by
      SDS-gel electrophoresis. Selected gel pieces were excised and their proteins were
      determined by MS. A total of 235 different proteins were found. Out of 235
      proteins, 37 appeared to be first identifications in human thyroid cells.
      Comparing SDS gel lanes of equally numbered free-flow IEF fractions revealed
      similar patterns with a number of identical bands if proteins of a distinct cell
      line had been applied, irrespective of whether the cells had been cultured under
      1g or s-microg. Most of the identical band pairs contained identical proteins.
      However, the concentrations of some types of proteins were different within the
      two pieces of gel. Proteins that concentrated differently in such pieces of gel
      are considered as candidates for further investigations of gravitational
      sensitivity.

PMID- 20049859
TI  - Distinct proteomic features of two fibrogenic liver cell populations: hepatic
      stellate cells and portal myofibroblasts.
AB  - In chronic liver diseases, the accumulation of extracellular matrix leading to
      fibrosis is caused by myofibroblasts, the origins of which are debatable. We
      performed a comparative proteomic study to identify markers and gain insight into
      distinct functions of myofibroblasts derived either from hepatic stellate cells
      (HSCs) or from portal mesenchymal cells. After isolation from normal liver and
      culture in similar conditions, myofibroblastic HSCs (MF-HSCs) presented enlarged
      cytoplasms whereas portal myofibroblasts (PMFs) were more proliferative, and
      formed more stress fibers. The two cell types were subjected to comparative
      analyses by 2-D MS/MS. Six proteins were overexpressed in PMFs, with
      myofibroblast-related typical functions. Among them, cofilin-1 showed the
      greatest difference in expression and a lower pI than expected. Immunoblot
      demonstrated higher levels of phosphorylation, a modification of the protein
      implicated in stress fiber formation. Eleven proteins, mostly involved in stress
      response, were overexpressed in MF-HSCs. Cytoglobin had the highest level of
      overexpression, as confirmed by reverse transcription quantitative real-time PCR,
      immunoblot and immunocytochemical analyses. These results identify cytoglobin as
      the best marker for distinguishing MF-HSCs from PMFs and suggest different
      functions for the two cell populations in the liver wound healing response, with
      a prominent role for PMFs in scar formation.

PMID- 20049860
TI  - The secreted and surface proteomes of the adult stage of the carcinogenic human
      liver fluke Opisthorchis viverrini.
AB  - Infection with the human liver fluke, Opisthorchis viverrini, is a serious public
      health problem in Thailand, Laos and nearby locations in Southeast Asia. Both
      experimental and epidemiological evidence strongly implicate liver fluke
      infection in the etiology of one of the liver cancer subtypes, cholangiocarcinoma
      (CCA). To identify parasite proteins critical for liver fluke survival and the
      etiology of CCA, OFFGEL electrophoresis and multiple reaction monitoring were
      employed to characterize 300 parasite proteins from the O. viverrini
      excretory/secretory products and, utilizing selective labeling and sequential
      solubilization, from the host-exposed tegument. The excretory/secretory included
      a complex mixture of proteins that have been associated with cancers, including
      proteases of different mechanistic classes and orthologues of mammalian growth
      factors and anti-apoptotic proteins. Also identified was a cysteine protease
      inhibitor which, in other helminth pathogens, induces nitric oxide production by
      macrophages, and, hence may contribute to malignant transformation of inflamed
      cells. More than 160 tegumental proteins were identified using sequential
      solubilization of isolated teguments, and a subset of these was localized to the
      surface membrane of the tegument by labeling living flukes with biotin and
      confirming surface localization with fluorescence microscopy. These included
      annexins, which are potential immuno-modulators, and orthologues of the
      schistosomiasis vaccine antigens Sm29 and tetraspanin-2. Novel roles in
      pathogenesis were suggested for the tegument-host interface since more than ten
      surface proteins had no homologues in the public databases. The O. viverrini
      proteins identified here provide an extensive catalogue of novel leads for
      research on the pathogenesis of opisthorchiasis and the development of novel
      interventions for this disease and CCA, as well as providing a scaffold for
      sequencing the genome of this fluke.

PMID- 20049861
TI  - Changes in the proteome of Salmonella enterica serovar Thompson as stress
      adaptation to sublethal concentrations of thymol.
AB  - Thymol is a natural biocide and component of some essential oils from herbs. Its
      inhibitory effect on the growth of different microorganisms is well documented.
      The precise targets of the antibacterial action of thymol is not yet been fully
      established, the action seems to take place in different ways. The strain
      Salmonella enterica serovar Thompson MCV1 was grown in the presence of a
      sublethal concentration (0.01%) of thymol. The proteins extracted from treated
      and untreated cells were subjected to 2-D PAGE, followed by in-gel spot digestion
      and subsequent MALDI-TOF analysis. The analysis of gels showed many proteins that
      were either upregulated or downregulated by the presence of thymol, with
      significant changes in proteins belonging to different functional classes. In
      particular, the thioredoxin-1 was not expressed in the treated cells, indicating
      that its absence could be a consequence of the stress caused by the presence of
      thymol. On the other hand, different chaperon proteins were upregulated or de
      novo synthesis such as GroEL and DnaK, key proteins in the protection mechanism
      toward thermal stress. Outer membrane proteins were upregulated in treated cells;
      indeed the bacterial envelope stress response is trigged by the accumulation of
      misfolded outer membrane proteins. Moreover, the thymol seems to impair the
      citrate metabolic pathway, as well as many enzymes involved in the synthesis of
      ATP. Definitely, thymol plays a role in altering very different pathways of cell
      metabolism.

PMID- 20049862
TI  - Differential protein expression on the cell surface of colorectal cancer cells
      associated to tumor metastasis.
AB  - Progression to metastasis is the critical point in colorectal cancer (CRC)
      survival. However, the proteome associated to CRC metastasis is very poorly
      understood at the moment. In this study, we used stable isotope labeling by amino
      acids in cell culture to compare two CRC cell lines: KM12C and KM12SM,
      representing poorly versus highly metastatic potential, to find and quantify the
      differences in protein expression, mostly at the cell surface level. After
      biotinylation followed by affinity purification, membrane proteins were separated
      by SDS-PAGE and analyzed using nanoflow LC-ESI-LTQ. A total of 291 membrane and
      membrane-associated proteins were identified with a p value<0.01, from which 60
      proteins were found to be differentially expressed by more than 1.5-fold. We
      identified a number of cell signaling, CDs, integrins and other cell adhesion
      molecules (cadherin 17, junction plakoglobin (JUP)) among the most deregulated
      proteins. They were validated by Western blot, confocal microscopy and flow
      cytometry analysis. Immunohistochemical analysis of paired tumoral samples
      confirmed that these differentially expressed proteins were also altered in human
      tumoral tissues. A good correlation with a major abundance in late tumor stages
      was observed for JUP and 17-beta-hydroxysteroid dehydrogenase type 8 (HSD17B8).
      Moreover, the combined increase in JUP, occludin and F11 receptor expression
      together with cadherin 17 expression could suggest a reversion to a more
      epithelial phenotype in highly metastatic cells. Relevant changes were observed
      also at the metabolic level in the pentose phosphate pathway and several amino
      acid transporters. In summary, the identified proteins provide us with a better
      understanding of the events involved in liver colonization and CRC metastasis.

PMID- 20049863
TI  - Unrestrictive identification of non-phosphorylation PTMs in yeast kinases by MS
      and PTMap.
AB  - A few protein PTMs, such as phosphorylation and ubiquitination, are known to be
      critical in regulation of protein kinase activities. However, the roles of other
      PTMs have not been extensively studied in kinases. Development of a comprehensive
      description of all types of PTMs and discovering novel in vivo PTMs in low
      abundance represent major analytical challenges. Toward this goal, we have
      developed a strategy for systematic and accurate identification of the full
      spectrum of PTMs in yeast protein kinases. Our strategy involves isolation of GST
      fused kinase proteins, MS analysis, and unrestrictive PTM identification by PTMap
      algorithm. Among the 30 purified yeast kinases, we identified 27 different types
      of PTMs, and 53 PTM sites, among which are 13 novel mass shifts that have not
      been previously reported, likely representing novel PTMs. These results represent
      a significant expansion of our current understanding of PTMs in kinases and
      suggest highly complex regulation of kinase function.

PMID- 20049864
TI  - Proteomic analysis of symbiosome membranes in Cnidaria-dinoflagellate
      endosymbiosis.
AB  - Symbiosomes are specific intracellular membrane-bound vacuoles containing
      microalgae in a mutualistic Cnidaria (host)-dinoflagellate (symbiont)
      association. The symbiosome membrane is originally derived from host plasma
      membranes during phagocytosis of the symbiont; however, its molecular components
      and functions are not clear. In order to investigate the protein components of
      the symbiosome membranes, homogenous symbiosomes were isolated from the sea
      anemone Aiptasia pulchella and their purities and membrane intactness examined by
      Western blot analysis for host contaminants and microscopic analysis using
      various fluorescent probes, respectively. Pure and intact symbiosomes were then
      subjected to biotinylation by a cell impermeant agent (Biotin-XX
      sulfosuccinimidyl ester) to label membrane surface proteins. The biotinylated
      proteins, both Triton X-100 soluble and insoluble fractions, were subjected to 2
      D SDS-PAGE and identified by MS using an LC-nano-ESI-MS/MS. A total of 17
      proteins were identified. Based on their different subcellular origins and
      functional categories, it indicates that symbiosome membranes serve as the
      interface for interaction between host and symbiont by fulfilling several crucial
      cellular functions such as those of membrane receptors/cell recognition,
      cytoskeletal remodeling, ATP synthesis/proton homeostasis, transporters, stress
      responses/chaperones, and anti-apoptosis. The results of proteomic analysis not
      only indicate the molecular identity of the symbiosome membrane, but also provide
      insight into the possible role of symbiosome membranes during the endosymbiotic
      association.

PMID- 20049865
TI  - Screening for therapeutic targets of vorinostat by SILAC-based proteomic analysis
      in human breast cancer cells.
AB  - Histone deacetylases (HDACs) play critical roles in silencing tumor suppressor
      genes. HDAC inhibitors reactivate tumor suppressor genes and inhibit tumor cell
      growth in vitro and in vivo, and several HDAC inhibitors are currently being
      evaluated in clinical trials for cancer therapy. A comprehensive analysis of
      proteins regulated by HDAC inhibitors would enhance our ability to define and
      characterize their essential therapeutic targets. Here, we employed stable
      isotope labeling with amino acids in cell culture-based quantitative proteomics
      to identify acetylated proteins in human breast cancer cells. Treatment with the
      clinically relevant HDAC inhibitor, suberoylanilide hydroxamic acid (vorinostat),
      induces lysine acetylation of 61 proteins in MDA-MB-231 human breast cancer
      cells. Suberoylanilide hydroxamic acid not only induces lysine acetylation in
      chromatin-associated proteins, but also acetylates previously unrecognized
      nonhistone proteins, including transcriptional factors and regulators,
      chaperones, cell structure proteins, and glycolytic enzymes in a time-dependent
      manner. Knowledge of the full repertoire of acetylated proteins will provide a
      foundation for further defining the functions of HDACs in cancer cells.

PMID- 20049866
TI  - Thioredoxin targets of the plant chloroplast lumen and their implications for
      plastid function.
AB  - The light-dependent regulation of stromal enzymes by thioredoxin (Trx)-catalysed
      disulphide/dithiol exchange is known as a classical mechanism for control of
      chloroplast metabolism. Recent proteome studies show that Trx targets are present
      not only in the stroma but in all chloroplast compartments, from the envelope to
      the thylakoid lumen. Trx-mediated redox control appears to be a common feature of
      important pathways, such as the Calvin cycle, starch synthesis and tetrapyrrole
      biosynthesis. However, the extent of thiol-dependent redox regulation in the
      thylakoid lumen has not been previously systematically explored. In this study,
      we addressed Trx-linked redox control in the chloroplast lumen of Arabidopsis
      thaliana. Using complementary proteomics approaches, we identified 19 Trx target
      proteins, thus covering more than 40% of the currently known lumenal chloroplast
      proteome. We show that the redox state of thiols is decisive for degradation of
      the extrinsic PsbO1 and PsbO2 subunits of photosystem II. Moreover, disulphide
      reduction inhibits activity of the xanthophyll cycle enzyme violaxanthin de
      epoxidase, which participates in thermal dissipation of excess absorbed light.
      Our results indicate that redox-controlled reactions in the chloroplast lumen
      play essential roles in the function of photosystem II and the regulation of
      adaptation to light intensity.

PMID- 20049867
TI  - Global phosphoproteomic effects of natural tyrosine kinase inhibitor, genistein,
      on signaling pathways.
AB  - Genistein is a natural protein tyrosine kinase inhibitor that exerts anti-cancer
      effect by inducing G2/M arrest and apoptosis. However, the phosphotyrosine
      signaling pathways mediated by genistein are largely unknown. In this study, we
      combined tyrosine phosphoprotein enrichment with MS-based quantitative proteomics
      technology to globally identify genistein-regulated tyrosine phosphoproteins
      aiming to depict genistein-inhibited phosphotyrosine cascades. Our experiments
      resulted in the identification of 213 phosphotyrosine sites on 181 genistein
      regulated proteins. Many identified phosphoproteins, including nine protein
      kinases, eight receptors, five protein phosphatases, seven transcriptical
      regulators and four signal adaptors, were novel inhibitory effectors with no
      previously known function in the anti-cancer mechanism of genistein. Functional
      analysis suggested that genistein-regulated protein tyrosine phosphorylation
      mainly by inhibiting the activity of tyrosine kinase EGFR, PDGFR, insulin
      receptor, Abl, Fgr, Itk, Fyn and Src. Core signaling molecules inhibited by
      genistein can be functionally categorized into the canonial Receptor-MAPK or
      Receptor-PI3K/AKT cascades. The method used here may be suitable for the
      identification of inhibitory effectors and tyrosine kinases regulated by anti
      cancer drugs.

PMID- 20049868
TI  - Sorting protein lists with nwCompare: a simple and fast algorithm for n-way
      comparison of proteomic data files.
AB  - MS, the reference technology for proteomics, routinely produces large numbers of
      protein lists whose fast comparison would prove very useful. Unfortunately, most
      softwares only allow comparisons of two to three lists at once. We introduce here
      nwCompare, a simple tool for n-way comparison of several protein lists without
      any query language, and exemplify its use with differential and shared cancer
      cell proteomes. As the software compares character strings, it can be applied to
      any type of data mining, such as genomic or metabolomic datalists.

PMID- 20049869
TI  - FragmentationAnalyzer: an open-source tool to analyze MS/MS fragmentation data.
AB  - A thorough understanding of the fragmentation processes in MS/MS can be a
      powerful tool in assessing the resulting peptide and protein identifications. We
      here present the freely available, open-source FragmentationAnalyzer tool
      (http://fragmentation-analyzer.googlecode.com) that makes it straightforward to
      analyze large MS/MS data sets for specific types of identified peptides, using a
      common set of peptide properties. This enables the detection of fragmentation
      pattern nuances related to specific instruments or due to the presence of post
      translational modifications.

PMID- 20049870
TI  - The activation of liver X receptors inhibits toll-like receptor-9-induced foam
      cell formation.
AB  - Toll-like receptors (TLRs) are related to foam cell formation (FCF), key event in
      the establishment/progression of atherosclerosis. The activation of TLR2 and TLR4
      can increase FCF. The aim of this study was to evaluate the role of TLR9 in FCF.
      Murine macrophages were treated with CpG-ODN, TLR9 agonist, and oxidized
      particles of LDL (Paz-PC) and FCF was analyzed by means of Oil Red O staining.
      The administration of CpG-ODN plus Paz-PC onto macrophages increased the amount
      of lipid droplets, correlated to increased levels of tumor necrosis factor (TNF)
      alpha, IFNbeta, and IP-10. The underlying mechanism by which TLR9 ligation
      influenced Paz-PC in the FCF was NF-kappaB- and IRF7-dependent, as observed by
      higher levels of phosphorylated IkappaBalpha, increased nuclear translocation of
      the p65 subunit, lower levels of the total IKKalpha protein and higher release of
      interferon-dependent cytokines, such as IP-10. Liver X receptors (LXRs) regulate
      lipid cellular transport and negatively modulate TLR-dependent signaling
      pathways. Indeed, the addition of GW3965, synthetic LXRs agonist, significantly
      reduced FCF after CpG-ODN plus Paz-PC stimulation. In this condition, we observed
      decreased levels of the nuclear translocation of the p65 subunit, related to the
      higher presence of LXRalpha into the nucleus. TNF-alpha, IP-10, and IFNbeta
      levels were reduced by the administration of GW3965 following CpG-ODN and Paz-PC
      treatment. In conclusion, the activation of TLR9 facilitates the formation of
      foam cells in an NF-kappaB- and IRF7-dependent manner, countered by the
      activation of LXRs. This study further support LXRs as potential anti
      atherosclerotic target.

PMID- 20049871
TI  - Mitogen-activated protein kinase-activated protein kinase 2 (MK2) in skeletal
      muscle atrophy and hypertrophy.
AB  - Skeletal muscle is a highly plastic tissue. Overall muscle growth (hypertrophy)
      or muscle wasting (atrophy) results from alterations in intracellular signaling
      pathways with important regulatory steps occurring in the nucleus as well as in
      the cytoplasm. Previous studies have identified components of the Akt/mTor
      pathway as well as the p38 MAPK pathway as important for skeletal muscle
      hypertrophy and/or atrophy. The present study tests the hypothesis that MK2, a
      substrate of p38 which following phosphorylation, can be exported from the
      nucleus in a complex with p38, may be important for skeletal muscle growth. The
      expression of MK2 was examined in denervated mouse hind-limb (atrophic) and
      hemidiaphragm (transiently hypertrophic) muscles. MK2 mRNA expression decreased
      after denervation in both atrophic (48% of innervated controls, P < 0.001) and
      hypertrophic muscle (34% of innervated controls, P < 0.01) but MK2 protein
      expression decreased only in atrophic muscle (32% of innervated controls, P <
      0.01). The level of T205 phosphorylated MK2 increased after denervation in both
      atrophic (fourfold increase, P < 0.01) and hypertrophic muscles (almost sevenfold
      increase, P < 0.001) whereas the level of T317 phosphorylated MK2 (necessary for
      nuclear export) increased after denervation in hypertrophic muscle (nearly
      threefold increase, P < 0.001) but not in atrophic muscle. Logarithmically
      transformed relative changes in MK2 phosphorylated at T317 correlated well (r(2)
      = 0.7737) with relative changes in muscle weight. The results suggest a role for
      MK2 in the regulation of muscle mass, a role which, at least in part, may be
      related to determining the subcellular localization of p38 in muscle fibers.

PMID- 20049872
TI  - NF-kappaB activation stimulates osteogenic differentiation of mesenchymal stem
      cells derived from human adipose tissue by increasing TAZ expression.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a skeletal catabolic agent that
      stimulates osteoclastogenesis and inhibits osteoblast function. Although TNF
      alpha inhibits the mineralization of osteoblasts, the effect of TNF-alpha on
      mesenchymal stem cells (MSC) is not clear. In this study, we determined the
      effect of TNF-alpha on osteogenic differentiation of stromal cells derived from
      human adipose tissue (hADSC) and the role of NF-kappaB activation on TNF-alpha
      activity. TNF-alpha treatment dose-dependently increased osteogenic
      differentiation over the first 3 days of treatment. TNF-alpha activated ERK and
      increased NF-kappaB promoter activity. PDTC, an NF-kappaB inhibitor, blocked the
      osteogenic differentiation induced by TNF-alpha and TLR-ligands, but U102, an ERK
      inhibitor, did not. Overexpression of miR-146a induced the inhibition of IRAK1
      expression and inhibited basal and TNF-alpha- and TLR ligand-induced osteogenic
      differentiation. TNF-alpha and TLR ligands increased the expression of
      transcriptional coactivator with PDZ-binding motif (TAZ), which was inhibited by
      the addition of PDTC. A ChIP assay showed that p65 was bound to the TAZ promoter.
      TNF-alpha also increased osteogenic differentiation of human gastroepiploic
      artery smooth muscle cells. Our data indicate that TNF-alpha enhances osteogenic
      differentiation of hADSC via the activation of NF-kappaB and a subsequent
      increase of TAZ expression.

PMID- 20049873
TI  - Discovery of a benzoxazine derivative promoting angiogenesis in vitro and in
      vivo.
AB  - Angiogenesis is a multi-step process that refers to the growth of new vessels
      from pre-existing ones. Endothelial proliferation, migration, and tube formation
      constitute a critical step in angiogenesis. Recently, we demonstrated that a
      novel benzoxazine derivative, 6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine
      (ABO) could improve the proliferation of human umbilical vein endothelial cells
      (HUVECs) without basic fibroblast growth factor (bFGF) and serum. In this study,
      we further tested its effect on endothelial angiogenesis with Matrigel assay,
      migration assay, and in vivo chick chorioallantoic membrane (CAM) assay. Our
      results showed that ABO effectively facilitated cell migration and promoted
      capillary-like tube formation in vitro and in vivo. To elucidate the underlying
      mechanisms, we examined intracellular reactive oxygen species (ROS)
      level/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and superoxide
      dismutase (SOD) activities, nitric oxide (NO) level/endothelial nitric oxide
      synthase (eNOS) activity, and mitochondrial membrane potential (MMP). Our data
      indicated that ABO depressed ROS with inhibition of NADPH oxidase instead of SOD
      activity, stimulated NO production and eNOS activation, and restored MMP in
      HUVECs. Our findings suggest that ABO is a promising tool for exploring the
      mechanisms of angiogenesis and may have a therapeutic potential in ischemic
      pathologies.

PMID- 20049874
TI  - Membrane lipid defects are responsible for the generation of reactive oxygen
      species in peripheral blood mononuclear cells from vitiligo patients.
AB  - The pathogenesis of vitiligo, an acquired depigmenting disease of the skin,
      involves oxidative stress. Based on that, the generation of reactive oxygen
      species (ROS) by the mitochondria may be relevant in the pathogenesis of
      vitiligo. Here, we evaluate the biochemical and functional alterations involved
      in the defective activity that has been previously described both in melanocytes
      and peripheral blood mononuclear cells (PBMC) from vitiligo patients. Moreover,
      we used a freeze-thaw test as a mild stress stimulus to disclose any latent
      defects in the assembly of membrane lipids that may compromise the functionality
      of the membrane itself. We show that the lipid constitution of the membrane is
      altered in vitiligo. Specifically, the cardiolipin (CL) level in the
      mitochondrial inner membrane is reduced and the level of cholesterol is
      increased. Furthermore, an increase in the expression level of 3-hydroxy-3methyl
      glutaryl-CoenzymeA-reductase (HMG-CoA reductase), the rate-limiting enzyme for
      cholesterol biosynthesis, was also seen. Associated with that, the expression of
      electron transport chain (ETC) lipid-dependent subunits was also modified, and
      their expression was further affected by the freeze-thaw stress. The expression
      of CL-independent mitochondrial proteins, such as porin and Bcl2, were unaffected
      in vitiligo PBMC. These data confirm that ETC protein expression mainly
      correlates with lipid arrangement and that loss of their expression is not due to
      generalized or random oxidative-mediated damage. We suggest that the modification
      of membrane lipid components in vitiligo cells may be the biochemical basis for
      the mitochondrial impairment and the subsequent production of intracellular ROS
      following the exposure to a mild stress.

PMID- 20049875
TI  - IFN-gamma-receptor signaling ameliorates transplant vasculopathy through
      attenuation of CD8+ T-cell-mediated injury of vascular endothelial cells.
AB  - Occlusive transplant vasculopathy (TV) is the major cause for chronic graft
      rejection. Since endothelial cells (EC) are the first graft cells encountered by
      activated host lymphocytes, it is important to delineate the molecular mechanisms
      that coordinate the interaction of EC with activated T cells. Here, the
      interaction of CD8(+) T cells with Ag-presenting EC in vivo was examined using a
      transgenic heart transplantation model with beta-galactosidase (beta-gal)
      expression exclusively in EC (Tie2-LacZ hearts). We found that priming with beta
      gal peptide-loaded DC failed to generate a strong systemic IFN-gamma response,
      but elicited pronounced TV in both IFN-gamma receptor (IFNGR)-competent, and
      ifngr(-/-) Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8(+) T
      cells with beta-gal-recombinant mouse cytomegalovirus (MCMV-LacZ) in recipients
      of ifngr(+/+) Tie2-LacZ hearts did not precipitate significant TV. However, MCMV
      LacZ infection of recipients of ifngr(-/-) Tie2-LacZ hearts led to massive
      activation of beta-gal-specific CD8 T cells, and led to development of fulminant
      TV. Further analyses revealed that the strong systemic IFN-gamma "storm"
      associated with MCMV infection induced upregulation of programmed death-1 ligand
      1 (PD-L1) on EC, and subsequent attenuation of programmed death-1 (PD-1)
      expressing EC-specific CD8(+) T cells. Thus, IFNGR signaling in ECs activates a
      potent peripheral negative feedback circuit that protects vascularized grafts
      from occlusive TV.

PMID- 20049876
TI  - T-bet, a Th1 transcription factor regulates the expression of Tim-3.
AB  - T-cell immunoglobulin, mucin domain-3 (Tim-3) is a membrane protein expressed at
      late stages of IFN-gamma secreting CD4(+) Th1 cell differentiation and
      constitutively on DC. Ligation of Tim-3 on Th1 cells terminates Th1 immune
      responses. In addition, Tim-3 plays a role in tolerance induction, although the
      mechanism by which this is accomplished has yet to be elucidated. While it is
      clear that Tim-3 plays an important role in the immune system, little is known
      regarding the molecular pathways that regulate Tim-3 expression. In the current
      study, we examine the role of Th1-associated transcription factors in regulating
      Tim-3 expression. Our experiments reveal that Tim-3 expression is regulated by
      the Th1-specific transcription factor T-bet. This introduces a novel paradigm
      into the generation of a Th1 response, whereby a transcription factor responsible
      for effector Th1 cell differentiation also increases the expression of a specific
      counter-regulatory molecule to ensure appropriate termination of pro-inflammatory
      Th1 immune responses.

PMID- 20049877
TI  - c-Rel is crucial for the induction of Foxp3(+) regulatory CD4(+) T cells but not
      T(H)17 cells.
AB  - The NF-kappaB/Rel family member c-Rel was described to be required for the
      development of T(H)1 responses. However, the role of c-Rel in the differentiation
      of T(H)17 and regulatory CD4(+)Foxp3(+) T cells (Treg) remains obscure. Here, we
      show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory
      T(H)17 cells is normal. In contrast, generation of inducible Treg (iTreg) within
      c-Rel-deficient CD4(+) T cells was severely hampered and correlated to reduced
      numbers of Foxp3(+) T cells in vivo. Mechanistically, in vitro conversion of
      naive CD4(+) T cells into iTreg was crucially dependent on c-Rel-mediated
      synthesis of endogenous IL-2. The addition of exogenous IL-2 was sufficient to
      rescue the development of c-Rel-deficient iTreg. Thus, c-Rel is essential for the
      development of Foxp3(+) Treg but not for T(H)17 cells via regulating the
      production of IL-2.

PMID- 20049879
TI  - Investigation of the formation and recognition of a dimeric G-quadruplex in the
      promoter of Bcl-2 proto-oncogene by electrospray ionization mass spectrometry.

PMID- 20049880
TI  - A quick and easy method to identify bacteria by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry.
AB  - Concerns with water quality have increased in recent years, in part due to the
      more frequent contamination of water by pathogens like E. coli and L.
      pneumophila. Current methods for the typing of bacteria in water samples are
      based on culture of samples on specific media. These techniques are time
      consuming, subject to the impact of interferents and do not totally meet all the
      requirements of prevention. There is a need for accurate and rapid identification
      of these microorganisms. This report deals with the detection of bacteria, more
      precisely of Legionella spp., and the development of an analytical strategy for a
      rapid and unambiguous identification of these pathogens in water from diverse
      origins. Therefore, a protein mass mapping using matrix-assisted laser
      desorption/ionisation mass spectrometry (MALDI MS) of whole bacteria combined
      with a home-made database of bacteria spectra is applied. A large variety of
      different bacteria and microorganisms is used to approach the actual composition
      of samples with numerous interferents. The objective is to propose a universal
      method for sampling preparation before MALDI MS analysis and optimised
      spectrometric conditions for reproducible intense peaks. Several experimental
      factors known to influence signal quality such as time and media of culture have
      been studied. The proposed method gives promising results for a sure
      differentiation of Legionella species and subspecies and a rapid identification
      of bacteria which are the most dangerous or difficult to eradicate. This method
      is easy to perform with an excellent reproducibility. The analytical protocol and
      the corresponding database were validated on samples from different origins
      (cooling tower, plumbing hot water).

PMID- 20049881
TI  - Matrix vapor deposition/recrystallization and dedicated spray preparation for
      high-resolution scanning microprobe matrix-assisted laser desorption/ionization
      imaging mass spectrometry (SMALDI-MS) of tissue and single cells.
AB  - Matrix preparation techniques such as air spraying or vapor deposition were
      investigated with respect to lateral migration, integration of analyte into
      matrix crystals and achievable lateral resolution for the purpose of high
      resolution biological imaging. The accessible mass range was found to be beyond
      5000 u with sufficient analytical sensitivity. Gas-assisted spraying methods
      (using oxygen-free gases) provide a good compromise between crystal integration
      of analyte and analyte migration within the sample. Controlling preparational
      parameters with this method, however, is difficult. Separation of the preparation
      procedure into two steps, instead, leads to an improved control of migration and
      incorporation. The first step is a dry vapor deposition of matrix onto the
      investigated sample. In a second step, incorporation of analyte into the matrix
      crystal is enhanced by a controlled recrystallization of matrix in a saturated
      water atmosphere. With this latter method an effective analytical resolution of 2
      microm in the x and y direction was achieved for scanning microprobe matrix
      assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS).
      Cultured A-498 cells of human renal carcinoma were successfully investigated by
      high-resolution MALDI imaging using the new preparation techniques.

PMID- 20049882
TI  - Evaporation of solvent molecules by ultrafast heating: effect on conformation of
      solvated protein.
AB  - Using molecular dynamics simulation, we compare two cases of ultrafast heating of
      a small water droplet containing a solvated protein (echistatin). If the water
      temperature after irradiation is above the critical temperature, explosive
      boiling liberates the protein within some 10 ps of its hydration shell, while its
      temperature remains relatively low. By comparing with the case where the water
      shell is heated to the same final temperature, but without complete evaporation,
      we demonstrate that the protein conformation is governed by the hydration shell
      rather than by the protein temperature.

PMID- 20049883
TI  - Investigation of collision-induced dissociations involving odd-electron ion
      formation under positive electrospray ionization conditions using accurate mass.
AB  - Collision induced dissociation (CID) has been extensively used for structure
      elucidation. CID in the electrospray ionization (ESI) and atmospheric pressure
      chemical ionization (APCI) modes has been found to generate mostly even-electron
      fragment ions while it has been occasionally reported to form odd-electron free
      radical ions. However, the structural requirements and the fragmentation
      mechanisms for free-radical CIDs have not been well characterized in the
      literature. For this purpose, we studied a series of aromatic and non-aromatic
      compounds such as sulfonamides, N-aryl amides, tert-butyl-substituted aromatic
      compounds, aryl alkyl ethers, and O-alkyl aryl oximes using the LTQ and LTQ
      Orbitrap linear ion trap mass spectrometers. The accurate measurement of the
      fragment ion masses established the unambiguous assignment of the fragment
      structures resulting from the test compounds. Our results showed that free
      radical fragmentation is structure dependent and is to a large extent correlated
      with the neighboring groups in the structures that stabilize the newly formed
      free radical ions.

PMID- 20049884
TI  - A microfluidic reactor for rapid, low-pressure proteolysis with on-chip
      electrospray ionization.
AB  - A microfluidic reactor that enables rapid digestion of proteins prior to on-line
      analysis by electrospray ionization mass spectrometry (ESI-MS) is introduced. The
      device incorporates a wide (1.5 cm), shallow (10 microm) reactor 'well' that is
      functionalized with pepsin-agarose, a design that facilitates low-pressure
      operation and high clogging resistance. Electrospray ionization is carried out
      directly from a short metal capillary integrated into the chip outlet.
      Fabrication, involving laser ablation of polymethyl methacrylate (PMMA), is
      exceedingly straightforward and inexpensive. High sequence coverage spectra of
      myoglobin (Mb), ubiquitin (Ub) and bovine serum albumin (BSA) digests were
      obtained after <4 s of residence time in the reactor. Stress testing showed
      little loss of performance over approximately 2 h continuous use at high flow
      rates (30 microL/min). The device provides a convenient platform for a range of
      applications in proteomics and structural biology, i.e. to enable high-throughput
      workflows or to limit back-exchange in spatially resolved hydrogen/deuterium
      exchange (HDX) experiments.

PMID- 20049885
TI  - Real-time measurement of peroxyacetyl nitrate using selected ion flow tube mass
      spectrometry.
AB  - The on-line detection of gaseous peroxyacetyl nitrate (PAN) using selected ion
      flow tube mass spectrometry (SIFT-MS) has been investigated using a synthetic
      sample of PAN in air at a humidity of approximately 30%. Using the H(3)O(+)
      reagent ion, signals due to PAN at m/z 122, 77 and 95 have been identified. These
      correspond to protonated PAN, protonated peractetic acid and its water cluster,
      respectively. These products and their energetics have been probed through
      quantum mechanical calculations. The rate coefficient of H(3)O(+) has been
      estimated to be 4.5 x 10(-9) cm(3) s(-1), leading to a PAN sensitivity of 138
      cps/ppbv. This gives a limit of detection of 20 pptv in 10 s using the [M+H](+)
      ion of PAN at m/z 122.

PMID- 20049886
TI  - Determination and imaging of metabolites from Vitis vinifera leaves by laser
      desorption/ionisation time-of-flight mass spectrometry.
AB  - Analysis of grapevine phytoalexins at the surface of Vitis vinifera leaves has
      been achieved by laser desorption/ionisation time-of-flight mass spectrometry
      (LDI-ToFMS) without matrix deposition. This simple and rapid sampling method was
      successfully applied to map small organic compounds at the surface of grapevine
      leaves. It was also demonstrated that the laser wavelength is a highly critical
      parameter. Both 266 and 337 nm laser wavelengths were used but the 266 nm
      wavelength gave increased spatial resolution and better sensitivity for the
      detection of the targeted metabolites (resveratrol and linked stilbene
      compounds). Mass spectrometry imaging of grapevine Cabernet Sauvignon leaves
      revealed specific locations with respect to Plasmopara viticola pathogen
      infection or light illumination.

PMID- 20049887
TI  - Application of matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry for the study of Helicobacter pylori.
AB  - The characteristics of matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry based investigation of extremely variable bacteria
      such as Helicobacter pylori were studied. H. pylori possesses a very high natural
      variability. Accurate tools for species identification and epidemiological
      characterization could help the scientific community to better understand the
      transmission pathways and virulence mechanisms of these bacteria. Seventeen
      clinical as well as two laboratory strains of H. pylori were analyzed by the
      MALDI Biotyper method for rapid species identification. Mass spectra collected
      were found containing 7-13 significant peaks per sample, and only six protein
      signals were identical for more than half of the strains. Four of them could be
      assigned to ribosomal proteins RL32, RL33, RL34, and RL36. The reproducible peak
      with m/z 6948 was identified as a histidine-rich metal-binding polypeptide by
      tandem mass spectrometry (MS/MS). In spite of the evident protein heterogeneity
      of H. pylori the mass spectra collected for a particular strain under several
      cultivations were highly reproducible. Moreover, all clinical strains were
      perfectly identified as H. pylori species through comparative analysis using the
      MALDI Biotyper software (Bruker Daltonics, Germany) by pattern matching against a
      database containing mass spectra from different microbial strains (n = 3287)
      including H. pylori 26695 and J99. The results of this study allow the conclusion
      that the MALDI-TOF direct bacterial profiling is suited for H. pylori
      identification and could be supported by mass spectra fragmentation of the
      observed polypeptide if necessary.

PMID- 20049888
TI  - Evaluation and performance of desorption electrospray ionization using a triple
      quadrupole mass spectrometer for quantitation of pharmaceuticals in plasma.
AB  - The present work describes the methodology and investigates the performance of
      desorption electrospray ionization (DESI) combined with a triple quadrupole mass
      spectrometer for the quantitation of small drug molecules in human plasma.
      Amoxepine, atenolol, carbamazepine, clozapine, prazosin, propranolol and
      verapamil were selected as target analytes while terfenadine was selected as the
      internal standard common to each of the analytes. Protein precipitation of human
      plasma using acetonitrile was utilized for all samples. Limits of detection were
      determined for all analytes in plasma and shown to be in the range 0.2-40 ng/mL.
      Quantitative analysis of amoxepine, prazosin and verapamil was performed over the
      range 20-7400 ng/mL and shown to be linear in all cases with R(2) >0.99. In most
      cases, the precision (relative standard deviation) and accuracy (relative error)
      of each method were less than or equal to 20%, respectively. The performance of
      the combined techniques made it possible to analyze each sample in 15 s
      illustrating DESI tandem mass spectrometry (MS/MS) as powerful tool for the
      quantitation of analytes in deproteinized human plasma.

PMID- 20049889
TI  - Fragmentation of plumeran indole alkaloids from Aspidosperma spruceanum by
      electrospray ionization tandem mass spectrometry.
AB  - The fragmentation of six plumeran indole alkaloids (PIAs) previously isolated
      from Aspidosperma spruceanum has been investigated by electrospray ionization
      tandem mass spectrometry (ESI-MS/MS) in the positive ion mode. The fragmentation
      pathways have been established on the basis of MS/MS experiments using fragment
      ions generated in-source and deuterium-labeled alkaloids as precursor ions and on
      the basis of accurate mass measurements. Our results demonstrated that the
      fragmentation routes observed for the protonated PIAs are essentially derived
      from a pericyclic reaction and from the opening of rings D and E, followed by 1,4
      hydrogen rearrangements. Product ions resulting from radical eliminations were
      also observed, contrary to the 'even-electron rule'. Our data reveals that some
      product ions from protonated PIAs provide crucial information for the
      characterization of the acyl substituent at N-1, the methoxyl and hydroxyl groups
      at the aromatic moiety, and give evidence of an ether bridge between C-18 and C
      21. The data reported here were used for the dereplication of these compounds in
      a stem bark methanolic extract of Aspidosperma spruceanum.

PMID- 20049890
TI  - ESIprot: a universal tool for charge state determination and molecular weight
      calculation of proteins from electrospray ionization mass spectrometry data.
AB  - Electrospray ionization (ESI) ion trap mass spectrometers with relatively low
      resolution are frequently used for the analysis of natural products and peptides.
      Although ESI spectra of multiply charged protein molecules also can be measured
      on this type of devices, only average spectra are produced for the majority of
      naturally occurring proteins. Evaluating such ESI protein spectra would provide
      valuable information about the native state of investigated proteins. However, no
      suitable and freely available software could be found which allows the charge
      state determination and molecular weight calculation of single proteins from
      average ESI-MS data. Therefore, an algorithm based on standard deviation
      optimization (scatter minimization) was implemented for the analysis of protein
      ESI-MS data. The resulting software ESIprot was tested with ESI-MS data of six
      intact reference proteins between 12.4 and 66.7 kDa. In all cases, the correct
      charge states could be determined. The obtained absolute mass errors were in a
      range between -0.2 and 1.2 Da, the relative errors below 30 ppm. The possible
      mass accuracy allows for valid conclusions about the actual condition of
      proteins. Moreover, the ESIprot algorithm demonstrates an extraordinary
      robustness and allows spectral interpretation from as little as two peaks, given
      sufficient quality of the provided m/z data, without the necessity for peak
      intensity data. ESIprot is independent from the raw data format and the computer
      platform, making it a versatile tool for mass spectrometrists. The program code
      was released under the open-source GPLv3 license to support future developments
      of mass spectrometry software.

PMID- 20049891
TI  - Desulfurization of cysteine-containing peptides resulting from sample preparation
      for protein characterization by mass spectrometry.
AB  - In this study, we have examined two cysteine modifications resulting from sample
      preparation for protein characterization by mass spectrometry (MS): (1) a
      previously observed conversion of cysteine into dehydroalanine, now found in the
      case of disulfide mapping and (2) a novel modification corresponding to
      conversion of cysteine into alanine. Using model peptides, the conversion of
      cysteine into dehydroalanine via beta-elimination of a disulfide bond was seen to
      result from the conditions of typical tryptic digestion (37 degrees C, pH 7.0
      9.0) without disulfide reduction and alkylation. Furthermore, the surprising
      conversion of cysteine into alanine was shown to occur by heating cysteine
      containing peptides in the presence of a phosphine (tris(2-carboxyethyl)phosphine
      hydrochloride (TCEP)). The formation of alanine from cysteine, investigated by
      performing experiments in H(2)O or D(2)O, suggested a radical-based
      desulfurization mechanism unrelated to beta-elimination. Importantly, an
      understanding of the mechanism and conditions favorable for cysteine
      desulfurization provides insight for the establishment of improved sample
      preparation procedures of protein analysis.

PMID- 20049892
TI  - The effects of differentiated water supply after anthesis and nitrogen
      fertilization on delta15N of wheat grain.
AB  - The delta(15)N signature of plants integrates various processes in soil and
      plant. In this study, the effect of different water regimes applied during the
      period of grain growth of winter wheat on grain delta(15)N was examined in a 4
      year field experiment. The treatments comprised water shortage (S), an ample
      water supply (W), and rain-fed crop (R). Zero fertilization (N0) and 200 kg N.ha(
      1) in mineral fertilizer (N1) treatments were studied. The grain (15)N was
      determined during grain growth and at maturity. The water regime, nitrogen
      application and year had a significant effect on mature grain delta(15)N (p <
      0.001). Water and nitrogen explained 54.6% of the variability of delta(15)N in
      the experiment, the year accounted for 10.7% and the interactions for another
      19.6% of the total variability. The analysis of non-mature grain delta(15)N
      showed significant effects of N and year but not of water. Nitrogen fertilization
      reduced the delta(15)N of mature grain in years by 0.7-6.3 per thousand in
      comparison with N0 plants; the reduction was more pronounced under stress
      (average reduction by 4.1 per thousand) than under rain-fed (2.4 per thousand)
      and ample water supply (2.2 per thousand). Water stress decreased the grain
      delta(15)N in fertilized wheat, by 0.1-2.1 per thousand and 0.6-3.6 per thousand
      in experimental years, on average by 1.30 per thousand and 1.79 per thousand in
      comparison with the R and W water supply, respectively. The effect of water
      supply was not significant in non-fertilized wheat. A significant negative linear
      relationship between grain N concentration and delta(15)N in maturity or during
      the grain growth (R(2) = 0.83, R(2) = 0.76, respectively) was found. The observed
      sources of grain delta(15)N variability should be taken into consideration when
      analyzing and interpreting the data on the delta(15)N signature of plant material
      from field conditions.

PMID- 20049893
TI  - A dynamic soil chamber system coupled with a tunable diode laser for online
      measurements of delta13C, delta18O, and efflux rate of soil-respired CO2.
AB  - High frequency observations of the stable isotopic composition of CO(2) effluxes
      from soil have been sparse due in part to measurement challenges. We have
      developed an open-system method that utilizes a flow-through chamber coupled to a
      tunable diode laser (TDL) to quantify the rate of soil CO(2) efflux and its
      delta(13)C and delta(18)O values (delta(13)C(R) and delta(18)O(R), respectively).
      We tested the method first in the laboratory using an artificial soil test column
      and then in a semi-arid woodland. We found that the CO(2) efflux rates of 1.2 to
      7.3 micromol m(-2) s(-1) measured by the chamber-TDL system were similar to
      measurements made using the chamber and an infrared gas analyzer (IRGA) (R(2) =
      0.99) and compared well with efflux rates generated from the soil test column
      (R(2) = 0.94). Measured delta(13)C and delta(18)O values of CO(2) efflux using
      the chamber-TDL system at 2 min intervals were not significantly different from
      source air values across all efflux rates after accounting for diffusive
      enrichment. Field measurements during drought demonstrated a strong dependency of
      CO(2) efflux and isotopic composition on soil water content. Addition of water to
      the soil beneath the chamber resulted in average changes of +6.9 micromol m(-2)
      s(-1), -5.0 per thousand, and -55.0 per thousand for soil CO(2) efflux,
      delta(13)C(R) and delta(18)O(R), respectively. All three variables initiated
      responses within 2 min of water addition, with peak responses observed within 10
      min for isotopes and 20 min for efflux. The observed delta(18)O(R) was more
      enriched than predicted from temperature-dependent H(2)O-CO(2) equilibration
      theory, similar to other recent observations of delta(18)O(R) from dry soils
      (Wingate L, Seibt U, Maseyk K, Ogee J, Almeida P, Yakir D, Pereira JS, Mencuccini
      M. Global Change Biol. 2008; 14: 2178). The soil chamber coupled with the TDL was
      found to be an effective method for capturing soil CO(2) efflux and its stable
      isotope composition at high temporal frequency.

PMID- 20049894
TI  - A new class of anthocyanin-procyanidin condensation products detected in red wine
      by electrospray ionization multi-stage mass spectrometry analysis.
AB  - In our previous work, we have identified, in a model wine solution containing
      malvidin 3-glucoside, epicatechin and acetaldehyde, a new condensation product-
      hydroxylethyl-malvidin-3-glucoside-ethyl-epicatechin. The objective of this work
      was to verify the presence of such new condensation products in red wine. For
      this purpose, red wine was fractionated into various fractions by column
      chromatography on LiChroprep RP 18 and on Toyopearl 40 (F). The phenolic
      composition of each fraction was verified by HPLC-DAD and direct-infusion ESI
      MS(n) analysis. In addition to the well-known anthocyanins and their acetyl and
      coumaroyl derivatives, and several direct and indirect anthocyanin-(epi)catechin
      condensation products, a new class of pigmented products, namely hydroxyethyl
      anthocyanin-ethyl-flavanol compounds, have been detected in red wine. The new
      class of pigmented products would be expected to be the major pigments
      responsible for the color of aged red wine.

PMID- 20049895
TI  - Voltage-dependent calcium and chloride currents in S17 bone marrow stromal cell
      line.
AB  - The bone marrow stromal cell line S17 has been used to study hematopoiesis in
      vitro. In this study, we demonstrate the presence of calcium and chloride
      currents in cultured S17 cells. Calcium currents were of low amplitude or barely
      detectable (50-100 pA). Hence to amplify the currents, we have used barium as a
      charge carrier. Barium currents were identified based on their distinct voltage
      dependence, and sensitivity to dihydropyridines. S17 cells also exhibited a
      slowly activating outward current without inactivation, most commonly seen when
      the sodium of the extracellular solution was replaced either by TEA (TEA/Cs
      saline) or NMDG (NMDG saline), or by addition of amiloride to the extracellular
      solution. This current was abolished either by 500 microM SITS (4,4'
      diisothiocyanatostilbene-2-2'-disulfonic acid) or 500 microM DPC (diphenylamine-2
      carboxylic acid) a cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel blocker, identifying it as a Cl(-) current. RT-PCR identified
      the presence of ENaC and CFTR transcripts. CFTR blockade reduced cell
      proliferation, suggesting that this channel plays a physiological role in
      regulation of S17 cell proliferation.

PMID- 20049896
TI  - EGF and its related growth factors mediate sodium transport in mpkCCDc14 cells
      via ErbB2 (neu/HER-2) receptor.
AB  - Amiloride-sensitive sodium entry, via the epithelial sodium channel (ENaC), is
      the rate-limiting step for Na(+) absorption. Epidermal growth factor (EGF) is
      involved in the regulation of Na(+) transport and ENaC activity. However it is
      still controversial exactly how EGF regulates ENaC and Na(+) absorption. The aim
      of the present study was to characterize the EGF regulation of Na(+) transport in
      cultured mouse renal collecting duct principal mpkCCD(c14) cells, a highly
      differentiated cell line which retains many characteristics of the cortical
      collecting duct (CCD). EGF dose dependently regulates basal transepithelial Na(+)
      transport in two phases: an acute phase (<4 h) and a chronic phase (>8 h).
      Similar effects were observed with TGF-alpha, HB-EGF, and amphiregulin which also
      belong to the EGF-related peptide growth factor family. Inhibition of MEK1/2 by
      PD98059 or U0126 increased acute effects and disrupted chronic effects of EGF on
      Na(+) reabsorption. Inhibition of PI3-kinase with LY294002 abolished acute effect
      of EGF. As assessed by Western blotting, ErbB2 is the most predominant member of
      the ErbB family detected in mpkCCD(c14) cells. Immunohistochemistry analysis
      revealed localization of ErbB2 in the CCD in Sprague-Dawley rat kidneys. Both
      acute and long-term effects of EGF were abolished when cells were treated with
      tyrphostin AG-825 and ErbB2 inhibitor II, chemically dissimilar selective
      inhibitors of the ErbB2 receptor. Thus, we conclude that EGF and its related
      growth factors are important for maintaining transepithelial Na(+) transport and
      that EGF biphasically modulates sodium transport in mpkCCD(c14) cells via the
      ErbB2 receptor.

PMID- 20049897
TI  - Regulation of ATPase activity of transglutaminase 2 by MT1-MMP: implications for
      mineralization of MC3T3-E1 osteoblast cultures.
AB  - A pro-mineralization function for transglutaminase 2 (TG2) has been suggested in
      numerous studies related to bone, cartilage, and vascular calcification. TG2 is
      an enzyme which can perform protein crosslinking functions, or act as a
      GTPase/ATPase depending upon different stimuli. We have previously demonstrated
      that TG2 can act as an ATPase in a Ca(2+)-rich environment and that it can
      regulate phosphate levels in osteoblast cultures. In this study, we investigate
      the role MT1-MMP in regulating the ATPase activity of TG2. We report that
      proteolytic cleavage of TG2 by MT1-MMP in vitro results in nearly a 3-fold
      increase in the ATPase activity of TG2 with a concomitant reduction in its
      protein-crosslinking activity. We show that MC3T3-E1 osteoblasts secreted full
      length TG2 and major smaller fragments of 66 and 56 kDa, the latter having ATP
      binding abilities. MT1-MMP inhibition by a neutralizing antibody suppressed
      mineralization of osteoblast cultures to 35% of control, and significantly
      reduced phosphate levels in conditioned medium (CM). Furthermore, MT1-MMP
      inhibition abolished two of TG2 fragments in the cultures, one of which, the 56
      kDa fragment, has ATPase activity. Neutralization of MT1-MMP at early phases of
      mineralization significantly reduced mineral deposition, but had no effect in
      later phases implying MT1-MMP and TG2 might contribute to the initiation of
      mineralization. The cleavage of TG2 by MT1-MMP likely occurs on the cell
      surface/pericellular matrix where MT1-MMP and TG2 were co-localized. Based on
      these data, we propose that MT1-MMP modulates the extracellular function TG2 as
      part of a regulatory mechanism activates the pro-mineralization function of TG2.

PMID- 20049898
TI  - Modelling opportunity in health under partial observability of circumstances.
AB  - This paper proposes a behavioural model of inequality of opportunity in health
      that integrates John Roemer's framework of inequality of opportunity with the
      Grossman model of health capital and demand for health. The model generates a
      recursive system of equations for health and lifestyles, which is then jointly
      estimated by full information maximum likelihood with freely correlated error
      terms. The analysis innovates by accounting for the presence of unobserved
      heterogeneity, therefore addressing the partial-circumstance problem, and by
      extending the examination of inequality of opportunity to health outcomes other
      than self-assessed health, such as long-standing illness, disability and mental
      health. The results provide evidence for the existence of third factors that
      simultaneously influence health outcomes and lifestyle choices, supporting the
      empirical relevance of the partial-circumstance problem. Accounting for these
      factors, the paper corroborates that the effect of parental and early
      circumstances on adult health disparities is paramount. However, the particular
      set of circumstances that affect each of the analysed health outcomes differs
      substantially. The results also show that differences in educational
      opportunities, and in social development in childhood, are crucial determinants
      of lifestyles in adulthood, which, in turn, shape the observed health
      inequalities.

PMID- 20049899
TI  - The C2 domains of classical and novel PKCs as versatile decoders of membrane
      signals.
AB  - The C2 domains of classical and novel protein kinases C play a very important
      role in decoding signals, which trigger the translocation of these enzymes to the
      plasma membrane and/or other membrane subcellular compartments. The C2 domain of
      classical PKCs has a long reputation as a paradigm of protein responding to
      intracytosolic Ca2+ elevations through a calcium-binding region, where this
      cation acts as a bridge with the phosphatidylserine located in the inner leaflet
      of the plasma membrane. However, more recently, it has been discovered that a
      second site on the C2 domain interacts specifically with the phosphoinositide,
      PtdIns(4,5)P(2). Furthermore, several in vivo studies have shown that both
      calcium and PtdIns(4,5)P(2)-interacting regions are essential for the
      translocation of classical PKCs to the membrane. Other molecules like arachidonic
      and retinoic acid have also been observed to bind to these domains, modulating
      the activity of classical PKCs. The C2 domains of novel PKCs, on the other hand,
      were supposed to play only a secondary role with respect to the C1 domain in the
      activation process of these enzymes. New insights reveal that these C2 domains
      may also receive regulatory inputs and play an important role in the localization
      and activation of these enzymes. In this way, the C2 domain of PKCepsilon has
      been observed to respond to phosphatidic acid and to act together with the C1
      domain in the membrane anchorage and activation of the protein. These domains are
      also regulated by lipid-independent events like protein-protein interactions and
      phosphorylation. In this review we will focus in describing the recent findings
      on structural and functional properties of the C2 domains of PKCs, mainly as
      lipid-interacting modules able to integrate a wide variety of signals in the
      cell.

PMID- 20049900
TI  - Foxa2 and Nurr1 synergistically yield A9 nigral dopamine neurons exhibiting
      improved differentiation, function, and cell survival.
AB  - Effective dopamine (DA) neuron differentiation from neural precursor cells (NPCs)
      is prerequisite for precursor/stem cell-based therapy of Parkinson's disease
      (PD). Nurr1, an orphan nuclear receptor, has been reported as a transcription
      factor that can drive DA neuron differentiation from non-dopaminergic NPCs in
      vitro. However, Nurr1 alone neither induces full neuronal maturation nor
      expression of proteins found specifically in midbrain DA neurons. In addition,
      Nurr1 expression is inefficient in inducing DA phenotype expression in NPCs
      derived from certain species such as mouse and human. We show here that Foxa2, a
      forkhead transcription factor whose role in midbrain DA neuron development was
      recently revealed, synergistically cooperates with Nurr1 to induce DA phenotype
      acquisition, midbrain-specific gene expression, and neuronal maturation. Thus,
      the combinatorial expression of Nurr1 and Foxa2 in NPCs efficiently yielded fully
      differentiated nigral (A9)-type midbrain neurons with clearly detectable DA
      neuronal activities. The effects of Foxa2 in DA neuron generation were observed
      regardless of the brain regions or species from which NPCs were derived.
      Furthermore, DA neurons generated by ectopic Foxa2 expression were more resistant
      to toxins. Importantly, Foxa2 expression resulted in a rapid cell cycle exit and
      reduced cell proliferation. Consistently, transplantation of NPCs transduced with
      Nurr1 and Foxa2 generated grafts enriched with midbrain-type DA neurons but
      reduced number of proliferating cells, and significantly reversed motor deficits
      in a rat PD model. Our findings can be applied to ongoing attempts to develop an
      efficient and safe precursor/stem cell-based therapy for PD.

PMID- 20049901
TI  - Life-sparing effect of human cord blood-mesenchymal stem cells in experimental
      acute kidney injury.
AB  - In search for new sources of mesenchymal stem cells (MSCs) for renal repair in
      acute kidney injury (AKI), we investigated the potential of human cord blood (CB)
      MSCs to cure mice with AKI. Infusion of CB-MSCs in immunodeficient mice with
      cisplatin-induced AKI ameliorated both renal function and tubular cell injury,
      and prolonged survival. Transplanted CB-MSCs localized in peritubular areas,
      limited capillary alterations and neutrophil infiltration. Apoptosis reduced and
      tubular cell proliferation increased by virtue of stem cell capacity to produce
      growth factors. The reno-protective effect of CB-MSCs was further confirmed by
      their ability to inhibit oxidative damage and to induce the prosurvival factor
      Akt in tubular cells. The evidence that CB-MSCs in vitro increased the production
      of growth factors and inhibited IL-1 beta and TNFalpha synthesis when cocultured
      with damaged proximal tubular cells indicates a regenerative and anti
      inflammatory action of stem cell treatment. Altogether these results highlight
      the potential of human CB-MSCs as future cell therapy for testing in human AKI.

PMID- 20049902
TI  - Hypoxia promotes efficient differentiation of human embryonic stem cells to
      functional endothelium.
AB  - Early development of mammalian embryos occurs in an environment of relative
      hypoxia. Nevertheless, human embryonic stem cells (hESC), which are derived from
      the inner cell mass of blastocyst, are routinely cultured under the same
      atmospheric conditions (21% O(2)) as somatic cells. We hypothesized that O(2)
      levels modulate gene expression and differentiation potential of hESC, and thus,
      we performed gene profiling of hESC maintained under normoxic or hypoxic (1% or
      5% O(2)) conditions. Our analysis revealed that hypoxia downregulates expression
      of pluripotency markers in hESC but increases significantly the expression of
      genes associated with angio- and vasculogenesis including vascular endothelial
      growth factor and angiopoitein-like proteins. Consequently, we were able to
      efficiently differentiate hESC to functional endothelial cells (EC) by varying
      O(2) levels; after 24 hours at 5% O(2), more than 50% of cells were CD34+.
      Transplantation of resulting endothelial-like cells improved both systolic
      function and fractional shortening in a rodent model of myocardial infarction.
      Moreover, analysis of the infarcted zone revealed that transplanted EC reduced
      the area of fibrous scar tissue by 50%. Thus, use of hypoxic conditions to
      specify the endothelial lineage suggests a novel strategy for cellular therapies
      aimed at repair of damaged vasculature in pathologies such as cerebral ischemia
      and myocardial infarction.

PMID- 20049903
TI  - Neurons generated from APP/APLP1/APLP2 triple knockout embryonic stem cells
      behave normally in vitro and in vivo: lack of evidence for a cell autonomous role
      of the amyloid precursor protein in neuronal differentiation.
AB  - Alzheimer's disease amyloid precursor protein (APP) has been implicated in many
      neurobiologic processes, but supporting evidence remains indirect. Studies are
      confounded by the existence of two partially redundant APP homologues, APLP1 and
      APLP2. APP/APLP1/APLP2 triple knockout (APP tKO) mice display cobblestone
      lissencephaly and are perinatally lethal. To circumvent this problem, we
      generated APP triple knockout embryonic stem (ES) cells and differentiated these
      to APP triple knockout neurons in vitro and in vivo. In comparison with wild-type
      (WT) ES cell-derived neurons, APP tKO neurons formed equally pure neuronal
      cultures, had unaltered in vitro migratory capacities, had a similar acquisition
      of polarity, and were capable of extending long neurites and forming active
      excitatory synapses. These data were confirmed in vivo in chimeric mice with APP
      tKO neurons expressing the enhanced green fluorescent protein (eGFP) present in a
      WT background brain. The results suggest that the loss of the APP family of
      proteins has no major effect on these critical neuronal processes and that the
      apparent multitude of functions in which APP has been implicated might be
      characterized by molecular redundancy. Our stem cell culture provides an
      excellent tool to circumvent the problem of lack of viability of APP/APLP triple
      knockout mice and will help to explore the function of this intriguing protein
      further in vitro and in vivo.

PMID- 20049904
TI  - Anti-retroviral activity of TRIM5 alpha.
AB  - Human immunodeficiency virus type 1 (HIV-1) shows a very narrow host range
      limited to humans and chimpanzees. Experimentally, HIV-1 does not infect Old
      World monkeys, such as rhesus (Rh) and cynomolgus (CM) monkeys, and fails to
      replicate in activated CD4 positive T lymphocytes obtained from these monkeys. In
      contrast, simian immunodeficiency virus isolated from a macaque monkey (SIVmac)
      can replicate well in both Rh and CM. In 2004, tripartite motif 5 alpha (TRIM5
      alpha) was identified as a host factor which plays an important role in the
      restricted host range of HIV-1. Rh and CM TRIM5 alpha restrict HIV-1 infection
      but not SIVmac, while in comparison, anti-viral activity of human TRIM5 alpha
      against those viruses is very weak. TRIM5 alpha consists of the RING, B-box 2,
      coiled-coil and SPRY (B30.2) domains. The RING domain is frequently found in E3
      ubiquitin ligase and TRIM5 alpha is degraded via the ubiquitin-proteasome pathway
      during HIV-1 restriction. TRIM5 alpha recognises the multimerised capsid (viral
      core) of an incoming virus by its alpha-isoform specific SPRY domain and is
      believed to be involved in innate immunity to control retroviral infection.
      Differences in amino acid sequences in the SPRY domain of TRIM5 alpha of
      different monkey species were found to affect species-specific restriction of
      retrovirus infection, while differences in amino acid sequences in the viral
      capsid protein determine viral sensitivity to restriction. Accurate structural
      analysis of the binding surface between the viral capsid protein and TRIM5 alpha
      SPRY is thus required for the development of new antiretroviral drugs that
      enhance anti-HIV-1 activity of human TRIM5 alpha.

PMID- 20049905
TI  - Enteroviruses, type 1 diabetes and hygiene: a complex relationship.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in which the immune system mounts
      an attack on the host's insulin-producing beta cells. Because most cases of T1D
      cannot be attributed only to individual genetics, it is strongly inferred that
      there is a significant environmental contribution, such as infection, impacting
      disease development. The human enteroviruses (HEV) are common picornaviruses
      often implicated as triggers of human T1D, although precisely which of the
      numerous HEV may be involved in human T1D development is unknown. Experiments
      using non-obese diabetic (NOD) mice, commonly used to model T1D, show that
      induction of T1D by HEV infection in NOD mice is a multifactorial process
      involving both the virus and the host. Interestingly, results demonstrate that
      HEV infection of NOD mice can also induce long-term protection from T1D under
      certain conditions, suggesting that a similar mechanism may occur in humans.
      Based upon both experimental animal and observational human studies, we postulate
      that HEV have a dual role in T1D development and can either cause or prevent
      autoimmune disease. Whichever outcome occurs depends upon multiple variables in
      the host-virus equation, many of which can be deduced from results obtained from
      NOD mouse studies. We propose that the background to the sharply rising T1D
      incidences observed in the 20th century correlates with increased levels of
      hygiene in human societies. Viewing T1D in this perspective suggests that
      potential preventative options could be developed.

PMID- 20049906
TI  - Brief motivational feedback for college students and adolescents: a harm
      reduction approach.
AB  - Alcohol consumption and its attendant problems are prevalent among adolescents
      and young adult college students. Harm reduction has been found efficacious with
      heavy drinking adolescents and college students. These harm reduction approaches
      do not demand abstinence and are designed to meet the individual where he or she
      is in the change process. The authors present a case illustration of a harm
      reduction intervention, the Brief Alcohol Screening and Intervention for College
      Students (BASICS), with a heavy-drinking female college student experiencing
      significant problems as a result of her drinking. BASICS is conducted in a
      motivational interviewing style and includes cognitive-behavioral skills training
      and personalized feedback.

PMID- 20049907
TI  - Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in
      urban minority patients.
AB  - Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated
      interferon and ribavirin have demonstrated sustained viral response rates (SVRs)
      of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may
      not be equivalent. The goal of this study was to assess the effectiveness of HCV
      treatment with pegylated interferon and ribavirin in a treatment-naive, human
      immunodeficiency virus (HIV)-negative, United States urban population with many
      ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from
      2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine
      or the attending-supervised Montefiore Medical Center Liver Clinic. Care was
      supervised by one experienced physician under conditions of everyday clinical
      practice, and appropriate ancillary resources were made available to all
      patients. Two hundred fifty-five patients were treated with a mean age of 50
      years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian,
      13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least
      one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype
      1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly
      higher in faculty practice (27%) than in clinic patients (15%) by intention-to
      treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34%
      clinic). 3.3% of 1,656 treatment-naive, HIV antibody-negative individuals
      ultimately achieved SVR. Current hepatitis C therapies may sometimes be
      unavailable to, inappropriate for, and ineffective in United States urban
      patients. Treatment with pegylated interferon and ribavirin was less effective in
      this population than is implied by multinational phase III controlled trials. New
      strategies are needed to care for such patients.

PMID- 20049908
TI  - Total obstetric brachial plexus palsy: results and strategy of microsurgical
      reconstruction.
AB  - From 2000 to 2006, 35 infants with total obstetric brachial plexus palsy
      underwent brachial plexus exploration and reconstruction. The mean age at surgery
      was 10.8 months (range 3-60 months), and the median age was 8 months. All infants
      were followed for at least 2.5 years (range 2.5-7.3 years) with an average follow
      up of 4.2 years. Assessment was performed using the Toronto Active Movement
      scale. Surgical procedures included neurolysis, neuroma excision and
      interposition nerve grafting and neurotization, using spinal accessory nerve,
      intercostals and contralateral C7 root. Satisfactory recovery was obtained in
      37.1% of cases for shoulder abduction; 54.3% for shoulder external rotation;
      75.1% for elbow flexion; 77.1% for elbow extension; 61.1% for finger flexion,
      31.4% for wrist extension and 45.8% for fingers extension. Using the Raimondi
      score, 18 cases (53%) achieved a score of three or more (functional hand). The
      mean Raimondi score significantly improved postoperatively as compared to the
      preoperative mean: 2.73 versus 1, and showed negative significant correlation
      with age at surgery. In total, obstetrical brachial plexus palsy, early
      intervention is recommended. Intercostal neurotization is preferred for
      restoration of elbow flexion. Tendon transfer may be required to improve external
      rotation in selected cases. Apparently, intact C8 and T1 roots should be left
      alone if the patient has partial hand recovery, no Horner syndrome, and was
      operated early (3- or 4-months old). Apparently, intact nonfunctioning lower
      roots with no response to electrical stimulation, especially in the presence of
      Horner syndrome, should be neurotized with the best available intraplexal donor.

PMID- 20049909
TI  - Free flap failure caused by heparin-induced thrombocytopenia.

PMID- 20049910
TI  - Free flap failure in an anticardiolipin antibody-positive patient with neoplasm-
      a case report.
AB  - We present herein a case of massive arterial thrombosis of a free rectus
      abdominal musculocutaneous flap used for reconstructive surgery of gingival
      carcinoma that could not be rescued. A 54-year-old woman underwent the operation.
      She had experienced two miscarriages in her 20s, but medical history was
      otherwise uneventful. Intraoperatively, the anastomosed artery often showed
      massive arterial thrombosis, and the flaps had become necrotic after bilateral
      flaps were used. Laboratory findings, 7 days postoperatively, showed high levels
      of immunoglobulin G anticardiolipin antibody. This value normalized by 2 months
      postoperatively after using chemotherapy. This case does not match the criteria
      for antiphospholipid syndrome, but some English-language reports have shown
      rising antiphospholipid antibody levels, particularly anticardiolipin antibodies,
      in patients with neoplasm. In those cases, levels have normalized after
      successful therapy. Antiphospholipid antibody levels should be examined before
      surgery to identify risks of hypercoagulability.

PMID- 20049911
TI  - Surgical complications in kidney transplantation in nonhuman primates.
AB  - Surgical complications are important causes of graft loss in the nonhuman primate
      kidney transplantation model. We reviewed the incidence and intervention methods
      in 182 kidney transplantations performed in our lab recently 2 years in
      Cynomolgus monkeys. There were six renal artery thromboses (3.3%), eight urine
      leakages (4.4%), and five ureteral stenoses (2.7%). All renal artery thrombosis
      cases were found within 3 days after surgery. Urine leakage appeared from the 5th
      to 12th day after surgery and all cases were caused by ureter rupture.
      Reexploration was performed in five cases to reanastomose ureter with stent. Four
      cases reached long-term survival. The rest one died of graft rejection. Ureteral
      stenoses were found in long-term survival cases. Ureter reanastomoses with stent
      were performed in two cases. The postoperative renal functions of these two
      monkeys recovered to normal and they survived until study termination. From this
      large number of study, our experience indicated that kidney transplantation in
      the nonhuman primate is a safe procedure with low complications. Reexploration is
      recommended for salvage of the graft with urine leakage and ureteral stenosis.

PMID- 20049912
TI  - Modified retrograde-flow medial plantar island flap for reconstruction of distal
      dorsal forefoot defects--two case reports.
AB  - Soft tissue reconstruction of the distal forefoot and toes poses a difficult
      problem. Skin grafts are not suitable when deep structures are exposed. Local
      flaps are not available, particularly for defects of the toes. Free flaps are
      spared for larger defects. Medial plantar flap has been widely used for plantar
      defects, especially weight-bearing surface of the heel. Distally based retrograde
      flow design of this flap allows the transfer of the pedicled flap distally and
      provides coverage of soft tissue over the metatarsal heads. In this report, we
      further modified the retrograde-flow medial plantar island flap to extend its use
      for distal dorsal forefoot defects. The technique and outcomes of two patients
      are presented.

PMID- 20049913
TI  - Chain conformation and bioactivity of water-soluble polysaccharide extracted from
      Rhizoma Panacis Japonici.
AB  - A water-soluble alpha-(1-->4)-D-glucan heteropolysaccharide with 37% degree of
      branch extracted by base from Rhizoma Panacis Japonici, coded as RPS3, was
      fractionated into six fractions by the method of nonsolvent addition. Their
      weight-average molecular mass (M(w)), polydispersity index (M(w)/M(n)), and
      radius of gyration (s(2)(z) (1/2)) were determined with laser light scattering
      (LLS) and size exclusion chromatography combined with LLS. The structure of the
      fraction was determined by methylation analyses and (13)C NMR. The dependences of
      intrinsic viscosity ([eta]) and s(2)(z) (1/2) on M(w) were established as [eta] =
      0.71 M(w) (0.27 +/- 0.01) (cm(3)/g) and s(2)(z) (1/2) = 1.53 M(w) (0.27 +/- 0.02)
      (nm) in the M(w) range from 5.62 x 10(4) to 3.05 x 10(6) (g/mol) for RPS3 in
      0.15M NaCl aqueous solution at 25 degrees C. On the basis of the current theory
      of the polymer solution, the fractal dimension (d(f)), unperturbed chain
      dimension (A), and characteristic ratio (C(infinity)) were calculated to be 3.0,
      1.48 A, and 15.1, respectively. The results revealed that the RPS3 chains existed
      as spherical conformation in the aqueous solution. Transmission electron
      microscope further provided the evidence of the sphere shape of the RPS3 and its
      fractionated molecules in water. In vitro cytotoxicity assay indicated that the
      fractions could inhibit the tumor cells and showed no harm to normal cells at low
      dose. The bioactivity was relative with molecular mass of the samples.

PMID- 20049914
TI  - Continuous local intraarterial infusion of anticoagulants for microvascular free
      tissue transfer in primary reconstruction of the lower limb following resection
      of sarcoma.
AB  - In free tissue transfers, preventing microvascular thrombosis is the first
      priority to achieve a successful result. Numerous protocols exist for preventing
      thrombosis postoperatively. We performed continuous local intraarterial infusion
      of anticoagulants in 11 patients undergoing wide resection of malignant soft
      tissue tumors, followed by primary microvascular reconstruction in the lower
      limb. A catheter designed for epidural anesthesia was inserted into the femoral
      artery and connected to a syringe pump. A daily dose of 100 ml comprising 2,000 U
      of heparin and 40 microg of prostaglandin E(1) was administered by means of
      continuous infusion for seven consecutive days as a standard regime. There were
      no cases of thrombosis during the continuous local intraarterial infusion of
      anticoagulants. There were no serious systemic complications. Although we have
      described limited cases and supporting data are lacking, we feel that this
      procedure might be useful for microsurgical reconstruction of the lower limb.

PMID- 20049915
TI  - Diagnostic assessment and therapeutic approach for immunodeficiency due to
      chylous dysplasia: A case report.
AB  - Among possible causes of a condition of immunodeficiency, we have to consider the
      presence of a serious chylous dysplasia, due to the great loss of proteins
      through the intestinal lumen. A 20-year-old male, suffered from diarrhoea (2-4
      times a day), weight loss (8 kilos in 5 years), and malnutrition
      (hypogammaglobulinemia, hypoalbuminemia, leukocytopenia with lymphocytopenia).
      Accurate diagnostic assessment allowed to diagnose a protein-losing enteropathy.
      Conventional oil contrast lymphangiography allowed to accurately assess the case
      and to establish a proper therapeutic approach. The operation consisted in
      multiple antigravitational ligatures of dilated and incompetent chylous vessels
      and chylous vessel-mesenteric vein microanastomoses. Parameters concerning
      albumin and leukocytes normalized in 1 week after operation and remained stable
      with time; there were no more episodes of diarrhoea and the patient recovered
      weight. An accurate diagnostic assessment and above all lymphangiography allow to
      diagnose properly difficult cases of immunodeficiency due to intestinal protido
      dispersion and to plan a correct therapeutic functional approach.

PMID- 20049916
TI  - Development of techniques for gastrojejunal bypass surgery in obese mice.
AB  - We have previously described a duodenojejunal bypass (DJB) surgical model in
      healthy C57BL/6 mice. However, our pilot study showed that the same surgical
      technique caused a high mortality rate in obese mice. In this study, to
      significantly improve animal survival rate following bariatric surgery and
      thereby providing a stable surgical model for the study of glucose homeostasis in
      obese mice, we have used modified techniques and developed the end-to-side
      gastrojejunal bypass (GJB) surgery in obese C57BL/6 with impaired glucose
      tolerance. The modification consisted of using the distal part of the jejunum for
      biliopancreatic diversion including: 1) ligation of the distal stomach at the
      level of the pylorus; 2) connection the jejunum to the anterior wall of stomach
      in an end-to-side fashion; and 3) diverting the biliopancreatic secretions
      through the blind limb into the distal jejunum through an end-to-side
      anastomosis. We found that by modifying the proximal end-to-end duodenojejunal
      anastomosis, described in our original model, to an end-to-side gastrojejunal
      anastomosis in these obese mice, we were able to significantly improve the
      postoperative mortality in this study. We have also demonstrated that performing
      the GJB surgery in obese mice resulted in significant weight loss, normalized
      blood glucose levels, and prevented acute pancreatitis. This newly developed GJB
      surgery in the obese mice offers a unique advantage to study the mechanisms of
      gastrointestinal surgery as treatment for type 2 diabetes.

PMID- 20049917
TI  - Anterolateral thigh adipofascial flap for the restoration of facial contour
      deformities.
AB  - From January 2000 to May 2008, 50 patients with facial contour deformities
      underwent soft tissue augmentation with 51 anterolateral thigh (ALT) adipofascial
      flaps. Fifty flaps survived with no complications; partial fat necrosis occurred
      in one flap. Mean follow-up was 16 months. Flaps ranged from 10 x 6 cm to 20 x 12
      cm. Perforators were found in 50 flaps, 43 musculocutaneous perforators (84.3%)
      and 7 septocutaneous perforators (13.7%), with a mean of 2.5 perforators per
      flap. In one flap (2.0%), no perforator was found. In this case, we used an
      anteromedial thigh adipofascial flap using the medial branch of the descending
      branch of lateral circumflex femoral artery as the vascular pedicle. Relatively
      symmetric facial contour was achieved in 20 cases. In 30 cases, adjunctive
      procedures including flap debulking, fat injection, and resuspension were
      necessary, and 23 patients achieved satisfactory outcomes. We conclude that the
      ALT adipofascial flap can be successfully elevated and transplanted for the
      correction of soft tissue facial defects. This flap can provide tissue to fill
      large defects, and posses the qualities of pliability, an excellent blood supply,
      ease of suspension and fixation, and minimal morbidity at the donor site.

PMID- 20049918
TI  - Mechanism of formation of the C-terminal beta-hairpin of the B3 domain of the
      immunoglobulin-binding protein G from Streptococcus. IV. Implication for the
      mechanism of folding of the parent protein.
AB  - A 34-residue alpha/beta peptide [IG(28-61)], derived from the C-terminal part of
      the B3 domain of the immunoglobulin binding protein G from Streptoccocus, was
      studied using CD and NMR spectroscopy at various temperatures and by differential
      scanning calorimetry. It was found that the C-terminal part (a 16-residue-long
      fragment) of this peptide, which corresponds to the sequence of the beta-hairpin
      in the native structure, forms structure similar to the beta-hairpin only at T =
      313 K, and the structure is stabilized by non-native long-range hydrophobic
      interactions (Val47-Val59). On the other hand, the N-terminal part of IG(28-61),
      which corresponds to the middle alpha-helix in the native structure, is
      unstructured at low temperature (283 K) and forms an alpha-helix-like structure
      at 305 K, and only one helical turn is observed at 313 K. At all temperatures at
      which NMR experiments were performed (283, 305, and 313 K), we do not observe any
      long-range connectivities which would have supported packing between the C
      terminal (beta-hairpin) and the N-terminal (alpha-helix) parts of the sequence.
      Such interactions are absent, in contrast to the folding pathway of the B domain
      of protein G, proposed recently by Kmiecik and Kolinski (Biophys J 2008, 94, 726
      736), based on Monte-Carlo dynamics studies. Alternative folding mechanisms are
      proposed and discussed.

PMID- 20049920
TI  - Fast membrane association is a crucial factor in the peptide pep-1 translocation
      mechanism: a kinetic study followed by surface plasmon resonance.
AB  - The use of peptide carriers, termed "cell-penetrating peptides (CPPs)" has
      attracted much attention due to their potential for cellular delivery of
      hydrophilic molecules with pharmacological interest, overcoming the membrane
      barrier. These peptides are able to deliver attached cargos in a nontoxic manner,
      with the uptake mechanisms being either endosomally or physically driven. Pep-1
      is a CPP of particular interest, not only due to outstanding delivery rates but
      also because its mechanism of membrane translocation is exclusively physically
      driven which appears to be dependent on a very high affinity for the phospholipid
      bilayer in the cell membrane. In this study, pep-1-lipid interactions were
      further explored by characterization of the pep-1-lipid association/dissociation
      by surface plasmon resonance. Although a high affinity of pep-1 for lipid
      bilayers was observed in all conditions tested, negatively charged phospholipids
      resulted in a larger peptide/lipid ratio. We also show that pep-1-membrane
      interaction is a fast process described by a multistep model initiated by peptide
      adsorption, primarily governed by electrostatic attractions, and followed by
      peptide insertion in the hydrophobic membrane core. In the context of a cell
      based process, the translocation of pep-1 is a physical mechanism promoted by
      peptide primary amphipathicity and asymmetric properties of the membrane. This
      explains the high efficiency rates of pep-1 when compared with other CPPs.

PMID- 20049921
TI  - Harm reduction therapy with families and friends of people with drug problems.
AB  - This article describes and illustrates the ongoing development of a treatment for
      working with families and friends of drug users using harm reduction principles.
      The author was instrumental in applying harm reduction principles to substance
      abuse and has used these same principles to help families deal with the
      pessimism, pain, and grief that accompany their relationship to a person with an
      active substance abuse problem. The treatment involves learning decision-making
      processes based on both self-care and love for the substance abuser and is based
      on the values of harm reduction, caring, and incrementalism, rather than those of
      codependency, tough love, and abrupt behavior change. A long-term family therapy
      group and two family consultations illustrate the treatment and its applications.

PMID- 20049919
TI  - NMR structure of duplex DNA containing the alpha-OH-PdG.dA base pair: a mutagenic
      intermediate of acrolein.
AB  - Acrolein, a cell metabolic product and main component of cigarette smoke, reacts
      with DNA generating alpha-OH-PdG lesions, which have the ability to pair with
      dATP during replication thereby causing G to T transversions. We describe the
      solution structure of an 11-mer DNA duplex containing the mutagenic alpha-OH
      PdG.dA base pair intermediate, as determined by solution nuclear magnetic
      resonance (NMR) spectroscopy and retrained molecular dynamics (MD) simulations.
      The NMR data support a mostly regular right-handed helix that is only perturbed
      at its center by the presence of the lesion. Undamaged residues of the duplex are
      in anti orientation, forming standard Watson-Crick base pairs alignments.
      Duplication of proton signals at and near the damaged base pair reveals the
      presence of two enantiomeric duplexes, thus establishing the exocyclic nature of
      the lesion. The alpha-OH-PdG adduct assumes a syn conformation pairing to its
      partner dA base that is protonated at pH 6.6. The three-dimensional structure
      obtained by restrained molecular dynamics simulations show hydrogen bond
      interactions that stabilize alpha-OH-PdG in a syn conformation and across the
      lesion containing base pair. We discuss the implications of the structures for
      the mutagenic bypass of acrolein lesions.

PMID- 20049922
TI  - State of the art in harm reduction psychotherapy: an emerging treatment for
      substance misuse.
AB  - Harm reduction psychotherapy is an exciting and emerging treatment for a broad
      spectrum of substance use problems. This article introduces an issue of the
      Journal of Clinical Psychology: In Session devoted to the state of the art of
      harm reduction psychotherapy. We describe the harm reduction paradigm, the
      context for and history of the development of harm reduction psychotherapy, and
      its clinical principles. We then outline and frame the contributions to the
      issue. Our goal is that this issue will encourage psychotherapists to employ more
      harm reduction principles in practice and will provide many evidence-based
      methods to do so.

PMID- 20049924
TI  - Partners in treatment: relational psychoanalysis and harm reduction therapy.
AB  - A relational psychoanalytic harm reduction orientation to the treatment of
      substance misusers is presented and illustrated with a clinical example. Both
      harm reduction therapy and relational psychoanalysis rely on a two-person model
      in which the therapist and client are collaborators in the treatment. In both,
      substance use is seen in the context of the user's internal psychodynamics and
      external environment, and there is an emphasis on treating the person as a whole
      individual whose substance use is one aspect of life, rather than focusing on the
      substance use itself as was often done in the past. Historically, psychoanalysis
      and substance abuse treatment were so different from each other that their paths
      rarely crossed. The introduction of harm reduction therapy to substance abuse and
      the relational orientation in psychoanalysis have brought the fields closer
      together such that the valuable contributions that each can make to the other can
      now be appreciated.

PMID- 20049923
TI  - Harm reduction therapy: a practice-friendly review of research.
AB  - Harm reduction is an umbrella term for interventions aiming to reduce the
      problematic effects of behaviors. Although harm reduction was originally and most
      frequently associated with substance use, it is increasingly being applied to a
      multitude of other behavioral disorders. This article reviews the state of
      empirical research on harm reduction practices including alcohol interventions
      for youth, college students, and a variety of other adult interventions. We also
      review nicotine replacement and opioid substitution, as well as needle exchanges
      and safe injection sites for intravenous drug users. Dozens of peer-reviewed
      controlled trial publications provide support for the effectiveness of harm
      reduction for a multitude of clients and disorders without indications of
      iatrogenic effects. Harm reduction interventions provide additional tools for
      clinicians working with clients who, for whatever reason, may not be ready,
      willing, or able to pursue full abstinence as a goal.

PMID- 20049926
TI  - Treatment of hemophilia in developing countries: a journey of a thousand miles.

PMID- 20049928
TI  - Teratoma with a malignant somatic component in pediatric patients: the
      Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience.
AB  - BACKGROUND: Teratoma with a malignant somatic component (TMSC) is rare but
      described in adults, whereas information on pediatric presentation is sparse.
      PROCEDURE: The Associazione Italiana Ematologia Oncologia Pediatrica identified
      14 cases of TMSC. Clinical files and pathology specimens were reviewed. RESULTS:
      The series (9 female, 5 male) showed the following disease: testis (2),
      sacrococcygeal (3), ovary (3), retroperitoneum (3), mediastinum (2), and foot
      soft tissue (1). Distribution of the somatic component was: carcinoma (4),
      pancreatic neuroendocrine tumor (1), neuroblastoma (3), rhabdomyosarcoma (3),
      rhabdomyosarcoma plus liposarcoma, chondrosarcoma, neurogenic sarcoma (1),
      chondrosarcoma plus neuroectodermal sarcoma (1), malignant peripheral nerve
      sheath tumor (1). Three patients were in stage I, four in stage II, three in
      stage III, and four in stage IV. All but one patient underwent surgery and only
      females showed carcinoma components. Nine patients relapsed or progressed and
      eight died. Six patients are alive and disease-free. Two patients underwent
      complete resection and four were treated based on transformed histologies.
      Relapse-free and overall survival rates were 35.7% and 42.8%, respectively
      (median follow-up, 31 months). CONCLUSIONS: Prognosis for germ cell tumors (GCTs)
      containing MSC is worse than that for GCTs. The pediatric disease appears to be
      more heterogeneous in tumor site distribution and MSC histology than in adults.
      Our series suggests no effects of age, histology, or gender on outcome. Surgery
      has an essential role in localized disease, with complete resection highly
      desirable. Chemotherapy optimized for histology should include reagents directed
      to the somatic malignancy, if chemosensitive. Malignant GCT warrants GCT-directed
      chemotherapy.

PMID- 20049927
TI  - Peripheral blood stem cell support for multiple cycles of dose intensive
      induction therapy is feasible with little risk of tumor contamination in advanced
      stage neuroblastoma: a report from the Childrens Oncology Group.
AB  - BACKGROUND: Poor outcome in Stage 4 neuroblastoma may be improved with increased
      dose intensity of therapy. We investigated the feasibility of sequential
      collection and infusion of peripheral blood stem cells (PBSCs) as hematopoietic
      support for non-myeloablative dose intensive induction chemotherapy given every
      21-28 days. METHODS: Twenty-two children with Stage 4 neuroblastoma (>or=1 year
      of age) received two cycles of high-dose cyclophosphamide (4 g/m(2)), doxorubicin
      (75 mg/m(2)), and vincristine (2 mg/m(2)) followed by three cycles of
      interpatient dose escalating carboplatin (Dose Level 0 = 800 mg/m(2); Dose Level
      1 = 1,000 mg/m(2)), high-dose cyclophosphamide (4 g/m(2)), and etoposide (600
      mg/m(2)). PBSC were harvested following cycle 2, 3, and 4 in Cohort 1 and infused
      after each subsequent cycle. In Cohort 2, PBSC were harvested after cycle 2 and
      split into three aliquots for infusion. Dose limiting toxicity (DLT) and ability
      to administer cycles within 28 days was assessed. RESULTS: Sufficient PBSC (>or=2
      x 10(6) CD34 cells/kg per infusion) were collected from 17/21 eligible patients
      with minimal toxicity and no detectable neuroblastoma cells by immunocytology.
      Carboplatin at 1000 mg/m(2) resulted in DLT of delayed platelet recovery >28 days
      in 4/8 patients. Despite de-escalation to 800 mg/m(2), platelet DLT occurred in
      4/7 Cohort 1 and 3/7 Cohort 2 patients. CONCLUSION: As defined in this protocol,
      doses of carboplatin were not tolerable with the PBSC dose administered. However,
      it was feasible to collect sufficient PBSC from small neuroblastoma patients to
      use as hematopoietic support with minimal risk of tumor contamination and
      toxicity.

PMID- 20049929
TI  - Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and
      chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma.
AB  - We report a 2-year-old female with a subcutaneous tumor who was initially
      misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement
      and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the
      diagnosis of acute lymphoblastic leukemia was established. This necessitated
      further analysis of the subcutaneous tumor. The tissue was positive for immature
      B-cell markers and an immunoglobulin heavy chain gene rearrangement, which
      confirmed the final diagnosis of common type acute lymphoblastic leukemia with
      bulk extramedullary disease. The patient was treated with chemotherapy and was in
      remission 30 months after the diagnosis.

PMID- 20049930
TI  - Ongoing remission after intensive ALL-type chemotherapy in pediatric intestinal T
      cell lymphoma.
AB  - A rare case of primary intestinal T-cell lymphoma (ITL) of an 8-year-old boy is
      reported. Medium- to large-sized tumor cells were betaF1+, CD3+, CD8+. TIA-1+,
      but CD4-, CD5-, CD30-, CD56-, CD20-, CD79a-, TdT-, consistent with an
      intraepithelial lymphocyte (IEL) origin. They showed monoclonal rearrangement of
      the T-cell receptor gamma-chain and no evidence of EBV infection. No clinical,
      histologic, laboratory, or genetic evidence of celiac disease was detected. In
      adults, ITL is often associated with enteropathy and has a very poor outcome. Our
      patient remains in first remission 30 months after finishing the acute
      lymphoblastic leukemia protocol COALL-07-03 high risk standard.

PMID- 20049931
TI  - Inpatient use of laxatives during opioid administration in children with sickle
      cell disease.
AB  - BACKGROUND: Constipation is a frequent adverse drug event seen with opioids, the
      first-line therapy for sickle cell pain crises. Proactive use of laxatives and
      stool softeners is recommended when opioids are prescribed. Our objective was to
      generate national estimates of the inpatient use of laxatives during opioid
      administration in children with sickle cell disease (SCD) and identify
      associations between individual and hospital-level factors and laxative
      prescription. PROCEDURE: We analyzed data from 29 children's hospitals in the
      Pediatric Health Information System, extracting patients 0-18 years of age with
      SCD hospitalized between 7/1/2007 and 6/30/2008. Our main outcome measure was the
      percentage of opioid-receiving patients who also received a laxative or stool
      softener. RESULTS: Six thousand ninety-three total SCD admissions received
      opioids. Two-thirds (66%) of patients received at least one laxative, and 31%
      received more than one. The most commonly prescribed constipation medication was
      polyethylene glycol-electrolyte solution (42.0%), followed by docusate (31.4%)
      and senna (13.6%). Logistic regression revealed that increasing age was
      associated with increased use of laxatives, as were length of stay >1 day (OR =
      3.12), medical as compared to surgical admissions (OR = 4.16), and discharge
      diagnosis of constipation (OR = 18.6). Patients were somewhat less likely to
      receive laxatives in small and large volume hospitals as compared to medium
      hospitals. CONCLUSIONS: A substantial number of hospitalized patients with SCD
      receiving opioids do not receive laxatives and there is unexpected variability in
      the use of these medications. Increased attention needs to be paid to
      constipation prophylaxis in patients with SCD, particularly in younger patients
      and post-surgical patients.

PMID- 20049932
TI  - A prospective study of a long-term follow-up of an observation program for
      neuroblastoma detected by mass screening.
AB  - BACKGROUND: A nationwide mass screening for neuroblastoma (NBL) in 6-month-old
      infants (MS6M) was performed in Japan from 1985 to 2003. Favorable biological
      features were identified for most of the detected tumors; consequently, we began
      an observation program for selected screened patients in 1993. Here, we report
      the clinicopathological findings and present status of patients enrolled in our
      observation program, with the goal of evaluating its usefulness. PROCEDURE:
      Between 1993 and 2003, 53 of 101 patients with NBL detected by MS6M were
      enrolled. The patients were divided into four groups according to changes in
      urinary VMA and HVA levels and tumor size. RESULTS: Urinary VMA and HVA levels
      decreased in 39 of 53 patients. In 17 of these 39 patients, the tumor became
      undetectable (Group A); in 22 patients the tumor was detectable (Group B). In
      seven patients, tumor marker levels varied, and tumor volume gradually increased
      (Group C). In six patients, tumor marker levels and tumor volume increased in the
      short term (Group D). One patient had multiple tumors (1M according to
      International Neuroblastoma Staging System). All tumors in Groups C and D, four
      tumors in Group B, and one tumor in the 1M patient were removed. No unfavorable
      biologic factors were noted in any excised tumor. CONCLUSIONS: The observation
      program of the present study, one of the largest series for MS6M, confirmed that
      over 70% of patients who fulfilled the criteria could be observed without
      surgery.

PMID- 20049933
TI  - Diffuse central nervous system protoplasmic astrocytoma.
AB  - Protoplasmic astrocytoma is an extremely rare form of grade II low grade glioma
      which usually presents as a discrete mass lesion. We describe a 3-year-old female
      with diffuse protoplasmic astrocytoma with parenchymal involvement and
      leptomeningeal spread. This tumour proved extremely difficult to diagnose and
      followed a progressive course. Three superficial biopsies did not give the
      diagnosis and this was only confirmed 8 months from presentation from a larger
      fourth biopsy taken deeper from the cerebellum. To our knowledge this case
      represents the distinct presentation of protoplasmic astrocytoma presenting as
      extensive diffuse meningeal disease.

PMID- 20049934
TI  - Complete free flap loss due to extensive hemodilution.
AB  - BACKGROUND: Free tissue transfer in reconstruction of lower extremity wounds is
      well established. Controversy surrounds type and regimen of intravenous fluid
      application during microsurgery. Hemodilution is supposed to influence
      haemostatic process. PATIENTS AND METHODS: We performed an analysis of 48
      patients treated with a free latissimus dorsi muscle flap to the lower leg for
      posttraumatic soft-tissue coverage. Postoperative latissimus dorsi muscle flap
      perfusion was controlled by clinical monitoring. Intraoperative infusion
      management was evaluated retrospectively. RESULTS: In 4 of 48 included patients,
      a complete loss of free latissimus dorsi muscle flap was registered. Concomitant
      increased saline infusion was detected (4,534 ml versus. 6,125 ml; P = 0.048).
      Similar findings for relation of total infusion volume to body weight were seen
      (44 ml/kg versus 69 ml/kg; P = 0.01). No significant colloid infusion was
      detected. CONCLUSIONS: We demonstrate the clinical relevance of extensive
      intraoperative hyperhydration, which can provoke a complete free flap loss.

PMID- 20049935
TI  - Thoracic neuroblastic tumors in childhood.
AB  - AIM: Thoracic neuroblastic tumors (NBTs) are reported to have better prognosis.
      We aimed to review clinical characteristics, treatment results, and outcome of
      our patients with thoracic NBT. PATIENTS AND METHODS: Files of 87 children
      treated at our hospital between 1973 and 2007 with the diagnoses of thoracic NBT
      were reviewed for clinical and pathological characteristics. Treatment results
      and outcomes of these cases were examined. RESULTS: All but one tumors were
      located in posterior mediastinum, one in the posterior chest wall. Median age of
      all was 2.1 years (range, 0.03-14; F/M: 1.42). Fifteen cases had ganglioneuromas
      (GN), 26 ganglioneuroblastomas (GNBL), and 46 neuroblastomas (NBLs). Stages were:
      I, 20.5%; II, 22.1%; III, 38.2%; IV, 14.7%; IVS, 4.5%. Stages III and IV were
      more common in cases over 1 year of age. In 20 patients diagnoses were
      incidental. Twenty-two of 87 (25.3%) had symptomatic spinal cord compression and
      15 (17.3%) had Horner syndrome. Ten-year overall and event-free survival rates
      were 71.2% and 67.4%, respectively. Survival rates did not differ depending on
      the age being younger or older than 1 year. Ten-year survival rates were 88.8% in
      stages I, II, IVS; 65.3% in stage III and 27.8% in stage IV (P = 0.0002).
      CONCLUSIONS: Thoracic NBLs had a favorable prognosis. This might be a result of
      earlier diagnosis and some distinct biological characteristics. Favorable
      prognosis would suggest less aggressive treatment for such patients. Further
      studies on the biological characteristics of NBLs in the thoracic site and their
      association with outcome should be done.

PMID- 20049937
TI  - Quantification and characterization of subvisible proteinaceous particles in
      opalescent mAb formulations using micro-flow imaging.
AB  - Micro-flow imaging (MFI) has been shown to be more sensitive than light
      obscuration (LO) methods for measuring subvisible proteinaceous particles in
      protein formulations. Given the potential challenges in detecting particulates in
      opalescent mAb formulations, the accuracy of MFI to size and count particles in
      opalescent solutions was investigated and compared to LO and membrane microscopy
      methods. Proteinaceous monoclonal antibody (mAb) particles, generated either by
      chemical denaturation or agitation stress, polystyrene and glass particles were
      used as model systems for measurements in opalescent mAb solutions. The sizing
      and counting accuracies of MFI were unaffected by the opalescence of the medium.
      Using glass particles as a model system for proteinaceous particles, MFI was able
      to detect relatively low particle concentrations (approximately 10/mL) in
      opalescent solutions. MFI showed excellent linearity (R(2) = 0.9969) for
      quantifying proteinaceous particles in opalescent solutions over a wide range of
      particle concentrations (approximately 20-160,000/mL). Analyses of MFI particle
      image intensities revealed significant differences in the transparency of
      proteinaceous particles as a function of their size and mode of generation. LO
      method significantly underestimated proteinaceous particles, particularly those
      in the 2-10 microm size range. The less opaque proteinaceous particles were
      relatively more underestimated by the LO method in opalescent solutions.

PMID- 20049936
TI  - Phase I trial of two schedules of vincristine, oral irinotecan, and temozolomide
      (VOIT) for children with relapsed or refractory solid tumors: a Children's
      Oncology Group phase I consortium study.
AB  - BACKGROUND: In preclinical models, temozolomide, and vincristine are additive or
      synergistic with irinotecan. We examined this three-drug combination in children
      with relapsed solid tumors. Patients received orally administered irinotecan
      together with temozolomide and vincristine on two different schedules, using
      cefixime to reduce irinotecan-associated diarrhea. METHODS: Oral irinotecan was
      given daily on days 1-5 and 8-12 (Schedule A), or on days 1-5 (Schedule B).
      Temozolomide was given on days 1-5, with vincristine 1.5 mg/m(2) administered on
      days 1 and 8 (Schedule A) or day 1 (Schedule B) in 21-day courses. RESULTS: On
      Schedule A, the maximum tolerated dose of oral irinotecan was 35 mg/m(2)/day
      combined with temozolomide 100 mg/m(2)/day and vincristine on days 1 and 8. Dose
      limiting toxicities in 4 of 12 patients included hepatotoxicity, abdominal pain,
      anorexia, hypokalemia, and thrombocytopenia at 50 mg/m(2)/day. Using Schedule B,
      0 of 6 patients experienced dose-limiting toxicity (DLT) at the highest doses
      studied of oral irinotecan 90 mg/m(2)/day, temozolomide 150 mg/m(2)/day x 5, and
      vincristine on day 1. First-course and cumulative toxicity was greater with
      Schedule A. UGT1A1*28 genotype did not correlate with DLT. At the irinotecan dose
      of 90 mg/m(2)/day, the mean SN-38 AUC(inf) was 63 ng/ml hr. Activity was seen in
      sarcoma patients, and overall eight patients received >or=6 courses. CONCLUSIONS:
      The 5-day schedule of VOIT was well tolerated and provided SN-38 exposures
      similar to those achieved with intravenous IRN. Activity on this and prior
      studies suggests a potential role for VOIT in a spectrum of childhood solid
      tumors.

PMID- 20049938
TI  - Diversity of effective treatments of panic attacks: what do they have in common?
AB  - By comparing efficacious psychological therapies of different kinds, inferences
      about common effective treatment mechanisms can be made. We selected six
      therapies for review on the basis of the diversity of their theoretical
      rationales and evidence for superior efficacy: psychoanalytic psychotherapy,
      hypercapnic breathing training, hypocapnic breathing training, reprocessing with
      and without eye-movement desensitization, muscle relaxation, and cognitive
      behavior therapy. The likely common element of all these therapies is that they
      reduce the immediate expectancy of a panic attack, disrupting the vicious circle
      of fearing fear. Modifying expectation is usually regarded as a placebo mechanism
      in psychotherapy, but may be a specific treatment mechanism for panic. The fact
      that this is seldom the rationale communicated to the patient creates a moral
      dilemma: Is it ethical for therapists to mislead patients to help them? Pragmatic
      justification of a successful practice is a way out of this dilemma. Therapies
      should be evaluated that deal with expectations directly by promoting positive
      thinking or by fostering non-expectancy.

PMID- 20049940
TI  - The effects of substituted cyclodextrins on the colloidal and conformational
      stability of selected proteins.
AB  - The effects of various types of substituted and nonsubstituted cyclodextrins
      (CDs) on the physical and colloidal stability of three different proteins were
      studied to further ascertain the mechanism by which cyclodextrins stabilize
      proteins. The three proteins examined in this study are the Clostridium difficile
      Toxoid A, Yersinia pestis low-calcium-response V or V antigen (LcrV), and
      fibroblast growth factor 10 (FGF-10). These three pharmaceutically relevant
      proteins differ in molecular weight, pI, as well as in their secondary and
      tertiary structure. The effects of three parent cyclodextrins (alpha, beta, and
      gamma), as well as several hydroxypropyl (HP-CDs) and sulfobutylether (SBE-CDs)
      cyclodextrins of varying degrees of substitution, on the three proteins were
      examined as a function of pH and temperature. Structural changes and aggregation
      behavior were monitored in the presence and absence of the 17 cyclodextrins using
      circular dichroism, intrinsic fluorescence spectroscopy, and static light
      scattering. Overall, the major effect of the cyclodextrins on the proteins was
      the ability of a majority of them to inhibit thermally induced aggregation. This
      study suggests that the stabilization of proteins by cyclodextrins is dictated by
      their type and degree of substitution, as well as the physical and chemical
      properties of the protein being examined.

PMID- 20049942
TI  - The scientific basis for the duration of stability data required at the time of
      submission.

PMID- 20049943
TI  - Safety evaluation of amphiphilic three-armed star-shaped copolymer micelles.
AB  - In our previous work, we had prepared a biodegradable amphiphilic three-armed
      star-shaped copolymers (SPCE) based on poly(epsilon-caprolactone) (PCL) and
      poly(ethylene glycol) (PEG), which could form micelles by self-assembly method
      and it was a potential carrier for hydrophobic drug. For further application, the
      safety of SPCE micelles was evaluated in vitro and in vivo here. (13)C-NMR was
      used to confirm the formation of the micelles in aqueous solution, and the
      morphology was observed on transmission electron microscope (TEM). Also,
      thermostability of blank SPCE micelles was determined by Malvern Nano-ZS 90 laser
      particle size analyzer. In vitro toxicity evaluation included hemolytic test and
      cytotoxicity. In vivo acute toxicity tests and histopathological study of SPCE
      micelles were carried out on BALB/C mice which were administrated SPCE micelles
      (1 g/kg b.w.) intravenously. In acute toxicity test, the mice were observed
      continuously for 7 days, obtained their body weight every day, at last the mice
      was sacrificed for the following study: the blood of the mice was assigned for
      blood chemistry and routine analysis, the heart, liver, spleen, lung, and kidneys
      were used for histopathological study. All results indicated that the
      biodegradable self-assembled SPCE micelles were nontoxic; therefore, it might be
      used as a safe candidate for drug delivery system.

PMID- 20049941
TI  - Delivery of therapeutic proteins.
AB  - The safety and efficacy of protein therapeutics are limited by three interrelated
      pharmaceutical issues, in vitro and in vivo instability, immunogenicity and
      shorter half-lives. Novel drug modifications for overcoming these issues are
      under investigation and include covalent attachment of poly(ethylene glycol)
      (PEG), polysialic acid, or glycolic acid, as well as developing new formulations
      containing nanoparticulate or colloidal systems (e.g., liposomes, polymeric
      microspheres, polymeric nanoparticles). Such strategies have the potential to
      develop as next generation protein therapeutics. This review includes a general
      discussion on these delivery approaches.

PMID- 20049944
TI  - CD95 is cytoprotective for intestinal epithelial cells in colitis.
AB  - BACKGROUND: CD95 is a member of the tumor necrosis factor receptor family. It is
      constitutively expressed on the basolateral membrane of intestinal epithelial
      cells (IECs) and under certain conditions induces apoptosis when crosslinked by
      its natural ligand, CD95L. A multitude of studies have been published addressing
      the question of where and under which conditions CD95L is produced in the gut in
      normal, inflammatory, and neoplastic situations and whether the apoptosis
      inducing activity of CD95 contributes to pathology. Although some of these
      studies have considerably influenced our view on the role of the CD95/CD95L
      system compelling evidence for an involvement of the CD95/CD95L system in the
      physiological epithelial cell turnover is lacking. METHODS: CD95 signaling
      deficiency in the colon was achieved in 2 ways. By transplanting bone marrow from
      wildtype mice into lethally irradiated mice expressing a signaling deficient
      mutant of CD95 (lpr(cg) mice) and by tissue-specific deletion of CD95 in IECs.
      Mice were treated with either 3 cycles of dextran sulfate sodium (DSS) to induce
      colitis or by injection of azoxymethane (AOM) followed by 3 cycles of DSS to
      induce colon cancer. Disease index and the formation of neoplastic lesions in the
      colon were determined and histological analysis was performed. RESULTS: In each
      mouse model lacking CD95 activity in the colon mice were hypersensitive to DSS
      induced colitis. In the CD95-deficient mice this did not have an effect on
      AOM/DSS-induced cancer formation. CONCLUSIONS: CD95 plays a role in protecting
      the colon from inflammation without contributing to colon cancer, under
      conclusions of increased inflammation.

PMID- 20049945
TI  - Cell death in the colonic epithelium during inflammatory bowel diseases: CD95/Fas
      and beyond.
AB  - CD95 is a member of the death receptor family. It is a prototypical inducer of
      apoptosis that, upon binding of its cognate ligand (CD95L), forms a death
      inducing signaling complex composed of adaptor molecules and initiator caspases
      that transmit the apoptosis signal. The CD95/CD95L system was implicated in the
      etiology of inflammatory bowel disease (IBD) based, primarily, on the finding
      that CD95 is highly expressed in the intestinal epithelial cells and that
      epithelial apoptosis is increased in IBD. In recent years it has been recognized
      that CD95, while playing an important role as an apoptosis-inducing receptor in
      the immune system, also has multiple nonapoptotic functions on nonimmune cells.
      This review critically discusses the data on the possible function of CD95 as an
      apoptosis-inducing receptor in IBD and discusses alternative mechanisms for
      epithelial cell loss in IBD.

PMID- 20049946
TI  - Total nasolacrimal duct obstruction in 2 patients with inflammatory bowel
      disease.

PMID- 20049947
TI  - Activated factor XI and tissue factor in inflammatory bowel disease.

PMID- 20049948
TI  - Evaluation of endoscopic and imaging modalities in the diagnosis of structural
      disorders of the ileal pouch.
AB  - BACKGROUND: Computerized tomography enterography (CTE), gastrograffin enema
      (GGE), magnetic resonance imaging (MRI), and pouch endoscopy (PES) have commonly
      been used to assess ileal pouch disorders. However, their diagnostic utility has
      not been systematically evaluated. The aims of this study were to compare these
      imaging techniques to each other and to optimize diagnosis of pouch disorders by
      using a combination of these diagnostic modalities. METHODS: Clinical data of
      patients from the Pouchitis Clinic from 2003 to 2008 who had a PES and at least 1
      additional imaging modalities (CTE, GGE, or MRI) used for evaluation of ileal
      pouch disorders were retrospectively evaluated. We analyzed the accuracy,
      sensitivity, specificity, negative predictive value (NPV), and positive
      predictive value (PPV) with which these tests were able diagnose pouch inlet and
      distal small bowel and pouch outlet strictures, pouch fistulas, sinuses, and
      leaks. Subsequently, accuracy was recalculated by combining 2 imaging modalities
      to see if this could enhance accuracy. RESULTS: A total of 66 patients underwent
      evaluation with PES and 1 other imaging modality as follows: PES + CTE (n = 23),
      PES + GGE (n = 34), and PES + MRI (n = 26). The mean age was 41.5 +/- 14.5 years,
      with 28 being female (42.4%). Sixty patients (90.9%) had J pouches and 59 (89.4%)
      had a preoperative diagnosis of ulcerative colitis. Overall, CTE, GGE, MRI, and
      PES all had reasonable accuracy for the diagnosis of small bowel and inlet
      strictures (73.9%-95.4%), outlet strictures (87.9%-92.3%), fistula (76.9%-84.8%),
      sinus (68.0%-93.9%), and pouch leak (83-93.9%). CTE had the lowest accuracy for
      small bowel and inlet strictures (73.9%) and MRI had the lowest accuracy for
      pouch sinus (68.0%). Combining 2 imaging tests can increase the accuracy of
      diagnosis to 100% for strictures, fistulas, sinus, and pouch leaks. CONCLUSIONS:
      CTE, GGE, MRI, and PES offer complementary information on disorders of the pouch
      and the combination of these tests increases diagnostic accuracy for complex
      cases.

PMID- 20049949
TI  - Direct comparison of two different mesalamine formulations for the maintenance of
      remission in patients with ulcerative colitis: a double-blind, randomized study.
AB  - BACKGROUND: Mesalamine has been used as the first-line medication for the
      treatment of ulcerative colitis (UC). We directly compared the efficacy and
      safety of two different mesalamine formulations in the maintenance of remission
      in patients with UC. METHODS: In a multicenter, double-blind, randomized study,
      131 patients with quiescent UC were assigned to two groups: 65 to receive a pH
      dependent release formulation of mesalamine at 2.4 g/day (pH-2.4 g) and 66 to
      receive a time-dependent release formulation of mesalamine at 2.25 g/day (Time
      2.25 g). Both formulations were administered three times daily for 48 weeks. The
      primary endpoint was the proportion of patients without bloody stools. RESULTS:
      In the full analysis set (n = 130), the proportion of patients without bloody
      stools was 76.9% in the pH-2.4 g and 69.2% in the Time-2.25 g, demonstrating the
      noninferiority of pH-2.4 g to Time-2.25 g. No statistically significant
      difference in time to bloody stools was found between the two formulations (P =
      0.27, log-rank test), but the time to bloody stools tended to be longer in pH-2.4
      g compared to Time-2.25 g, and a similar trend was observed with regard to the
      time to relapse. No differences were observed between the safety profiles of the
      two formulations. CONCLUSIONS: The pH- and time-dependent release of mesalamine
      formulations were similarly safe and effective. Interestingly, the remission
      phase tended to be longer in the group that received the pH-dependent formulation
      compared to the group that received the time-dependent formulation (UMIN Clinical
      Trials Registry, no. C000000289).

PMID- 20049950
TI  - Direct comparison of two different mesalamine formulations for the induction of
      remission in patients with ulcerative colitis: a double-blind, randomized study.
AB  - BACKGROUND: Mesalamine is the first-line drug for the treatment of ulcerative
      colitis (UC). We directly compared the efficacy and safety of two mesalamine
      formulations for the induction of remission in patients with UC. METHODS: In a
      multicenter, double-blind, randomized study, 229 patients with mild-to-moderate
      active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release
      formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65
      received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33
      received placebo (Placebo). The drugs were administered three times daily for
      eight weeks. The primary endpoint was a decrease in the UC disease activity index
      (UC-DAI). RESULTS: In the full analysis set (n = 225) the decrease in UC-DAI in
      each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in
      Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over
      Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among
      the patients with proctitis-type UC, a significant decrease in UC-DAI was
      observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g.
      No differences were observed in the safety profiles. CONCLUSIONS: Higher dose of
      the pH-dependent release formulation was more effective for induction of
      remission in patients with mild-to-moderate active UC. Additionally, the pH
      dependent release formulation was preferable to the time-dependent release
      formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry,
      no. C000000288).

PMID- 20049951
TI  - Thiopurine maintenance therapy for ulcerative colitis: the clinical significance
      of monitoring 6-thioguanine nucleotide.
AB  - BACKGROUND: 6-Mercaptopurine (6-MP) is an effective maintenance medication in
      patients with ulcerative colitis (UC), but toxic effects like myelosuppression
      limit its clinical benefit. In the blood, 6-thioguanine (6-TGN) is formed from 6
      MP and mediates the therapeutic efficacy and most of the toxicities of 6-MP. The
      level of 6-TGN depends on the activity of thiopurine methyltransferase (TPMT),
      inherited as 1 of its 3 polymorphic forms with low, moderate, or normal/high
      activity. Accordingly, the 6-MP dose needs to be pharmacogenetically guided.
      METHODS: Patients with quiescent UC received 6-MP as maintenance therapy and 6
      TGN was assayed as its concentrations in red blood cells (RBCs) done by high
      performance liquid chromatography. In a preliminary investigation, 30 mg/day 6-MP
      (n = 50) was given orally over 12 weeks to determine the time course of blood 6
      TGN level. Then 257 patients were given 6-MP at 15-80 mg/day in a stepwise manner
      based on RBC 6-TGN, white blood cell count, and body weight to monitor 6-MP
      efficacy and safety profiles. RESULTS: At 30 mg/day 6-MP, RBC 6-TGN peaked over 4
      8 weeks. In the main dosing study, the mean RBC 6-TGN level in patients who
      remained in remission during the 1-year observation time (n = 151) was 322.3 +/-
      119.5 pmole/8 x 10(8) RBC versus 204.8 +/- 78.7 pmole/8 x 10(8) RBC in patients
      (n = 19) who relapsed (P < 0.001). Bone marrow suppression was seen almost
      exclusively at high 6-TGN concentration ranges. Further, a regression plot showed
      an inverse relationship between 6-TGN levels in RBC and TPMT enzyme activity.
      CONCLUSIONS: By regularly measuring RBC 6-TGN in patients with quiescent UC
      receiving 6-MP as maintenance therapy, we could monitor bone marrow suppression
      as well as other toxic side effects. Potentially, this strategy should enable
      physicians to avoid thiopurine-related adverse effects and identify individuals
      who may benefit most from 6-MP maintenance therapy.

PMID- 20049952
TI  - Surgical management of pyogenic complications of Crohn's disease.
AB  - Patients with Crohn's disease are prone to the development of pyogenic
      complications. These complications are most commonly in the form of perianal or
      intraabdominal abscesses and/or fistulas. Complications in these 2 distinct areas
      are managed differently; however, they are similar in the fact that initial
      treatment relies on medical or minimally invasive management to achieve a
      nonacute condition prior to definitive surgical procedure. This article reviews
      the current surgical management of obtaining pyogenic control in both anorectal
      and intraabdominal Crohn's disease.

PMID- 20049953
TI  - Generation and characterization of mice with null mutation of the chloride
      intracellular channel 1 gene.
AB  - CLIC1 belongs to a family of highly conserved and widely expressed intracellular
      chloride ion channel proteins existing in both soluble and membrane integrated
      forms. To study the physiological and biological role of CLIC1 in vivo, we
      undertook conditional gene targeting to engineer Clic1 gene knock-out mice. This
      represents creation of the first gene knock-out of a vertebrate CLIC protein
      family member. We first generated a Clic1 Knock-in (Clic1(FN)) allele, followed
      by Clic1 knock-out (Clic1(-/-)) mice by crossing Clic1(FN) allele with TNAP-cre
      mice, resulting in germline gene deletion through Cre-mediated recombination.
      Mice heterozygous or homozygous for these alleles are viable and fertile and
      appear normal. However, Clic1(-) (/-) mice show a mild platelet dysfunction
      characterized by prolonged bleeding times and decreased platelet activation in
      response to adenosine diphosphate stimulation linked to P2Y(12) receptor
      signaling.

PMID- 20049954
TI  - Radiofrequency recanalization of an occluded long segment left pulmonary artery
      in bidirectional cavopulmonary anastomosis.
AB  - In patients with hypoplastic left heart syndrome who experience the Norwood
      surgical palliative program, development of the pulmonary artery branches is
      crucial. Balloon dilation and stenting may relieve potential stenosis but
      complete occlusion remains difficult to address with transcatheter therapy. We
      report the use of radiofrequency followed by balloon dilation and stenting to
      treat a long segment left pulmonary artery occlusion in a 15-month-old boy
      bidirectional Glenn. The left pulmonary artery was successfully recanalized with
      an excellent short-term outcome. This further enhances the interest of
      radiofrequency for recanalization of occluded pulmonary artery branches, as an
      alternative to surgical reconstruction.

PMID- 20049955
TI  - Treatment of pulmonary vein stenosis with expanded polytetrafluoroethylene
      covered stents.
AB  - Atrium expanded polytetrafluoroethylene covered stents were implanted in the
      stenotic pulmonary veins (n = 5) of three patients. Use of this device was
      feasible in infants and the procedure was well-tolerated without major
      complications. The majority (4/5) of covered stents remained patent for at least
      3 months after implantation. Stents remain patent in the two surviving patients 6
      months after deployment.

PMID- 20049956
TI  - Percutaneous closure of patent foramen ovale and the risk of atrial fibrillation.

PMID- 20049957
TI  - Dual catheter technique for the treatment of severe coronary artery perforations.
AB  - OBJECTIVES: To evaluate the outcome of patients with coronary perforations who
      were treated with the dual catheter approach. BACKGROUND: Coronary artery
      perforation is a grave complication of percutaneous coronary intervention (PCI)
      with high mortality and morbidity. Treating a coronary artery perforation with
      two catheters through dual access enables a rapid delivery of covered stent or
      coils to the vessel, without losing control of the perforation site. METHODS: We
      retrospectively reviewed all patients who had a severe coronary perforation
      during a PCI in our center, and compared outcomes of patients treated with the
      dual versus the traditional single guiding catheter approach. RESULTS: Between
      April 2004 and October 2008, 13,466 PCI's were performed in Columbia University -
      New York Presbyterian Medical Center. There were 33 documented cases of coronary
      perforations during that period of time (0.245%), among these, 26 were
      angiographically severe (Ellis type 2 or 3 perforations). Eleven patients were
      treated acutely with a dual catheter technique whereas the other fifteen patients
      were treated using a single guiding catheter. In the dual catheter group one
      patient expired after emergent CABG (9.1%), and four patients underwent emergent
      paricardiocentesis (36.4%). In patients treated with single catheter, there were
      three deaths (20%), two surgical explorations (13.3%), eight emergent
      pericardiocenthesis (53.3%), and one event of severe anoxic brain damage (6.7%).
      CONCLUSION: The dual catheter technique is a relatively safe and reproducible
      approach to treat a PCI induced severe coronary artery perforation, and may
      improve outcome compared to historical series.

PMID- 20049958
TI  - The OstialPro positioning system for a renal artery stenosis.
AB  - Aorto-ostial lesions pose complex technical challenges in percutaneous
      revascularization procedures. The successful use of the ostial positioning system
      OstialPro has been reported in coronary arteries. This nitinol device has self
      expanding legs that open just distal to the guide catheter. This allows the stent
      to be deployed in the ostium of the vessel with the guide catheter positioned in
      the aorta and allows for accurate anatomic visualization of the plane between the
      ostium and the aorta. Besides coronary interventions, the OstialPro could be
      useful in peripheral vascular interventions for ostial renal, mesenteric or
      vertebral arteries stenoses. We report the case of a patient with a significant
      ostial renal artery stenosis who underwent a successful percutaneous intervention
      using the OstialPro device.

PMID- 20049959
TI  - Use of the sheathless guide catheter during routine transradial percutaneous
      coronary intervention: a feasibility study.
AB  - OBJECTIVE: The aim of this study is to investigate the feasibility of using a 6.5
      Fr sheathless guide catheter as a default system in transradial (TRA)
      percutaneous coronary intervention (PCI). BACKGROUND: TRA PCI has been shown to
      reduce mortality rates through a reduction in access site related bleeding
      complications compared with procedures performed though a femoral approach.
      Complications associated with the TRA route increase with the size of sheath
      used. These complications may be reduced by the use of a sheathless guide
      catheter system (Asahi Intecc, Japan) that is 1-2 Fr sizes smaller in diameter
      than the corresponding introducer sheath. METHODS: We performed PCI in 100
      consecutive cases using 6.5 Fr sheathless guides to determine the procedural
      success, rates of symptomatic radial spasm and radial occlusion. RESULTS:
      Procedural success using the 6.5 Fr sheathless guide catheter system was 100%
      with no cases requiring conversion to a conventional guide and catheter system.
      There were no procedural complications recorded associated with the use of the
      catheter. Adjunctive devices used in this cohort included IVUS, stent delivery
      catheters, distal protection devices, and simple thrombectomy catheters. The rate
      of radial spasm was 5% and the rate of radial occlusion at 2 months was 2%.
      CONCLUSION: Use of the 6.5 Fr sheathless guide catheter system, which has an
      outer diameter <5 Fr sheath, as the default system in routine PCI is feasible
      with a high rate of procedural success via the radial artery.

PMID- 20049960
TI  - Coronary intervention with 4-French catheters.
AB  - OBJECTIVES: We sought to determine whether 4-Fr percutaneous coronary
      intervention (PCI) is associated with technical difficulties that might have an
      unfavorable impact on procedural parameters. BACKGROUND: Four-Fr PCI is often
      associated with difficulties in catheter manipulation, which may lead to greater
      time consumption and increased dye usage when compared with PCI employing larger
      guiding catheters. METHODS: From July 2007 to March 2009, 62 patients underwent 4
      Fr PCI. Procedural characteristics were compared between patients who underwent 4
      Fr PCI in 2007 (early phase: 31 lesions in 26 patients) and those underwent in
      2008 or later (later phase: 40 lesions in 36 patients). RESULTS: Ad-hoc coronary
      intervention (3% vs. 23%, P < 0.05) and deep-vessel intubation (46% vs. 91%, P <
      0.05) were observed less frequently in the late phase than the early phase.
      Fluoroscopy time (8 +/- 6 min vs. 17 +/- 15 min, P < 0.05) and the amount of
      contrast dye used (64 +/- 33 mL vs. 90 +/- 46 mL, P < 0.05) were significantly
      reduced in the late phase than the early phase. No access site-related
      complications were observed in patients in either phase. CONCLUSIONS: The
      performance of 4-Fr PCI requires a certain learning curve, following which a
      reduction in fluoroscopy time and use of contrast dye may be achieved. This
      improvement in procedural parameters and the low incidence of access site-related
      complications might allow 4-Fr PCI to serve as a minimally invasive approach for
      the treatment of coronary artery diseases.

PMID- 20049961
TI  - Systemic rapamycin without loading dose for restenosis prevention after coronary
      bare metal stent implantation.
AB  - OBJECTIVES: The aim of this study was to assess the role of short oral
      administration of rapamycin, without loading dose, in the reduction of restenosis
      rate after bare metal stent implantation. BACKGROUND: Previous studies suggest
      that the administration of oral rapamycin reduces angiographic restenosis after
      bare metal stent implantation. METHODS: This was prospective, open-label study of
      80 patients randomized to either oral rapamycin (2 mg/day for 30 days, starting
      within 24 hr of stent implantation) or no therapy after implantation of a
      coronary bare metal stent. The primary study end point was incidence of
      angiographic binary restenosis and late loss at six months. The secondary end
      points were target lesion revascularization (TLR), target vessel
      revascularization (TVR), and incidence of major adverse cardiovascular events
      (MACE) at 6 months. RESULTS: Angiographic follow up was completed in 72/80 (90%)
      of patients. In the rapamycin group, the drug was well tolerated (22.5% minor
      side effects) and was maintained in 100% of patients. At six months, the in
      segment binary restenosis was 10.5% in rapamycin group vs. 51.4% in no-therapy
      group, P < 0.001) and the in-stent binary restenosis was 7.9% in rapamycin group
      vs. 48.7% in no-therapy group, P < 0.001. The in-segment late loss was also
      significantly reduced with oral therapy (0.29 + or - 0.39 vs. 0.86 + or - 0.64
      mm, respectively, P < 0.001). Similarly, after six months, patients in the oral
      rapamycin group also showed a significantly lower incidence of TLR and TVR (7%
      vs. 22.7%, respectively, P = 0.039) and MACE (7% vs. 22.7%, respectively, P =
      0.039). CONCLUSIONS: This study showed that the administration of oral rapamycin
      (2 mg/day, without loading dose) during 30 days after stent implantation
      significantly reduces angiographic and clinical parameters of restenosis.

PMID- 20049962
TI  - Left main intervention in myocardial infarction.
AB  - We report an 84-year-old patient who suddenly developed nausea, vomiting,
      hypotension, and needed intubation, assisted ventilation and pharmacological
      vasopressor support. Admission EKG showed anterior and lateral leads ST segment
      depression and 2 mm ST segment elevation in avR lead. Angiogram showed
      unprotected left-main coronary-artery (LM) sub-occlusive disease and totally
      occluded ostial right-coronary-artery (RCA), distally filled through the left
      coronary system. Unprotected LM disease was immediately treated with bare metal
      stent. The stent jailed the left-circunflex coronary-artery (LCx) ostium but did
      not compromise the arterial flow. Lately, the patient was discharged in a very
      good health condition. Ten months angiographic follow-up showed an extremely
      compromised LCx ostium treated successfully with drug eluted stent (DES) and mid
      left anterior descendent (LAD) severe lesion, treated with DES.

PMID- 20049963
TI  - Clinical cerebrovascular anatomy.
AB  - Stroke is often the result of carotid atheroma, which may cause ischemia via
      progressive arterial narrowing or lead to superimposed thrombus formation and
      subsequent atheroembolism to the intracerebral vasculature. Revascularization
      through carotid endarterectomy or carotid artery stenting with embolic protection
      devices has produced favorable results in appropriately selected patients. In
      planning the percutaneous approach, an arch aortogram is first acquired to
      determine arch type and identify the presence of any anatomic variants which may
      affect the approach to the procedure and catheter selection. Subsequent imaging
      of the cerebral vasculature is performed to delineate the collateral circulation
      that is present, including an evaluation of the Circle of Willis. Although
      Doppler ultrasound, computed tomography (CT), and magnetic resonance angiography
      (MRA) may be useful in evaluating the presence of carotid or cerebrovascular
      disease, digital subtraction angiography is required prior to performance of a
      percutaneous intervention in order to create a procedural "roadmap".
      Additionally, the comprehensive management of cerebrovascular disease requires a
      detailed knowledge of the specific clinical syndromes that result from ischemia
      in each vascular territory. This methodical review of cerebrovascular anatomy and
      stroke syndromes will provide the operator with the tools to conduct a thorough
      neurological assessment prior to revascularization, evaluate any periprocedural
      complications that may arise, and evaluate the patient with suspected stroke.

PMID- 20049964
TI  - Fine-needle aspiration of follicular patterned lesions of the thyroid: Diagnosis,
      management, and follow-up according to National Cancer Institute (NCI)
      recommendations.
AB  - The National Cancer Institute (NCI) State of the Science Conference on thyroid
      fine-needle aspiration (FNA) proposed that follicular patterned lesions can be
      divided into two diagnostic categories; follicular lesion of undetermined
      significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for
      follicular neoplasm/follicular neoplasm (SFON/FON). The former group can benefit
      from repeat FNA (RFNA) to achieve a more definitive diagnosis and the latter
      should undergo surgical excision for histologic characterization (adenoma vs.
      carcinoma). In this study, we report the combined experience from our
      institutions with thyroid FNA cases that can be placed into NCI-designated
      thyroid FNA diagnostic categories for follicular patterned lesions.The case
      cohort comprised of 857 cases in 645 females and 212 males; 509 cases could be
      classified as FLUS/AUS and 348 as SFON/FON. Histologic follow-up was available in
      273/509 (54%) cases diagnosed as FLUS/AUS and 251/348 (72%) cases diagnosed as
      SFON/FON.RFNA was performed in 203/509 (40%) patients classified as FLUS/AUS.
      RFNA diagnoses were: benign (125 cases), FLUS (46 cases), SFON/FON (20 cases),
      suspicious for papillary carcinoma (7 cases), papillary carcinoma (3 cases) and
      non-diagnostic (2 cases). The malignancy rate on surgical excision in the
      FLUS/AUS group was 27 and 15% with and without RFNA, respectively; and 25% in
      cases diagnosed as SFON/FON.RFNA is effective in managing thyroid nodules
      diagnosed as FLUS/AUS since the malignancy rates are different in cases with or
      without RFNA (27% vs. 15%). The malignancy rate (25%) in cases diagnosed as
      SFON/FON is similar to reported by other authors.

PMID- 20049965
TI  - Micronucleus in atypical urothelial cells.
AB  - The objective of this study is to evaluate the role of micronuclei (MN) in
      identifying the atypical urothelial cells urinary cytology. This is a
      retrospective study of a total of 30 cases of urine samples. Of these, 15 cases
      were selected where the initial diagnosis was atypical urothelial cell and later
      turned out as malignant cells on follow-up histopathology. The rest of the 15
      cases were reported as normal urothelial cells. The number of MN in 1,000
      urothelial cells was counted in all the cases and was expressed as percentage.
      All the cases diagnosed as atypical urothelial cells show the presence of MN. The
      mean number of MN was 2.53 +/- 0.99%. No MN was noted in any of the normal
      urothelial cells in control cases. The Student's t-test of MN scoring was highly
      significant (P < 0.000) in test (atypical urothelial cells) versus control group
      (benign urothelial cells). MN is an important biomarker of malignancy.
      Micronuclear score in atypical urothelial cells in urine cytology smears may help
      in proper diagnosis of the case.

PMID- 20049966
TI  - Interobserver and intraobserver variability in the calculation of the lipid-laden
      macrophage index: implications for its use in the evaluation of aspiration in
      children.
AB  - The lipid-laden macrophage index (LLMI) is a semiquantitative test used to
      evaluate aspiration in children. We assessed the reliability and reproducibility
      of LLMI by calculating interobserver and intraobserver variability among
      pathologists, with and without expertise in cytopathology. Forty-nine
      bronchoalveolar washes/lavages were blindly reviewed by four reviewers and
      assigned an LLMI. Three pathologists (two cytopathologists, one pathology fellow)
      reviewed slides twice and one cytotechnologist reviewed them once. Intraclass
      correlation coefficient (ICC) with 95% confidence interval (C.I.) was used to
      measure overall intraobserver and interobserver agreement. Interobserver
      agreement was also calculated separately for each pair of reviewers. ICC values
      did not indicate an acceptable level of interobserver agreement among
      pathologists, with (ICC = 0.67, 95% C.I.: 0.56-0.77) and without (ICC = 0.77, 95%
      C.I.: 0.61-0.84) the cytotechnologist included in the analysis. An ICC of 0.84
      (95% C.I.: 0.78-0.89) indicated an acceptable level of intraobserver agreement
      among pathologists. When calculated separately for each pair of reviewers, all
      but two ICC values for interobserver agreement were less than 0.75 (the minimally
      acceptable value for a reliable clinical measurement), and the lower confidence
      limit of each of the 95% C.I. was far below the 0.75 cutoff. Using Lin's
      coefficient, intraobserver variability was only acceptable for two pathologists.
      Our study highlights the lack of precision and subjectivity of the LLMI, as well
      as the significant inter and intraobserver bias that may occur among experienced
      and inexperienced pathologists, and cytotechnologists. Clinicians and
      cytopathologists alike should be mindful of this potential pitfall and interpret
      LLMI scores with caution.

PMID- 20049967
TI  - Fractal dimension of cell clusters in effusion cytology.
AB  - In this study, the fractal dimension (FD) of the ball-like tight clusters of
      known metastatic adenocarcinoma cells is compared with the tight cell clusters of
      the benign cells in the effusion fluid to find out the role of FD in
      differentiating malignant from benign cluster in effusion. A total of 68 and 72
      images of cluster of cells from 12 cases of benign and 13 cases of metastatic
      pleural and peritoneal effusion were studied for FD. The mean FD of the cluster
      of cells of benign and malignant effusion was 1.4801 +/- 0.23260 and 1.7175 +/-
      0.09006, respectively. Mann-Whitney U-test showed significant difference of FD
      between the cell clusters of malignant and benign effusion cases (P < 0.0001).
      Cytological features along with the measurement of FD of cell clusters in
      effusion cytology may be helpful in differentiating benign from malignant cases.

PMID- 20049968
TI  - Utility of on-line three-dimensional transesophageal echocardiography during
      percutaneous atrial septal defect closure.
AB  - Key echocardiographic assessments during percutaneous atrial septal defect (ASD)
      closure are the maximal defect diameter, the presence or absence of tissue rims,
      and the spatial relationships between the implanted device and cardiac
      structures. These assessments drive device selection and may help identify
      situations that may place a patient at risk for device erosion or other
      complications. On-line three-dimensional (3D) transesophageal echocardiography
      (TEE) enables the rendering of nearly unlimited tissue planes within an acquired
      pyramidal-shaped volume with minimal image post-processing. We present several
      cases of percutaneous ASD closure guided by on-line 3D TEE imaging that highlight
      the potential advantages of this new imaging technology.

PMID- 20049969
TI  - The sensitivity of cytologic evaluation of pleural fluid in the diagnosis of
      malignant mesothelioma.
AB  - Pleural malignant mesothelioma (MM), which is an aggressive neoplasm with a high
      mortality, frequently manifests initially as pleural effusions. The sensitivity
      of cytologic examination for its diagnosis varies widely in literature and most
      of the figures are from earlier studies with conventional cytologic preparations.
      The objective of this study was to provide the current evidence on the role and
      sensitivity of cytologic examination of pleural fluid in the diagnosis of MM. We
      reviewed the cytologic findings in pleural effusions of a large series of
      histologically proven MM (234 cases) diagnosed in our institution between 2001
      and 2008. Of all cases, 154 (66%) had cytologic material examined. A specific
      diagnosis of MM was rendered or suspected in 53% (79 patients). The lowest
      sensitivity (20%) was noticed in sarcomatoid MM cases. MM was favored over
      adenocarcinoma in 97% of patients with positive cytologic findings that have been
      confirmed with immunohistochemistry. In this series, five cases were inadequate
      and five cases were initially reported as atypical, whereas 65 cases (44%) were
      reported as negative for malignancy. On review of the cytology slides, only four
      cases were upgraded from benign to suspicious compared to four cases downgraded
      from suspicious to atypical but no significant improvement to the diagnosis could
      be made on revision. These data suggested that a cytologic diagnosis contributed
      useful information in patients with epithelioid and biphasic pleural MM.
      Limitations of the cytologic examination of MM should also be acknowledged.

PMID- 20049970
TI  - A new technique for vascular access management in transcatheter aortic valve
      implantation.
AB  - OBJECTIVES: To describe results from a novel percutaneous technique designed to
      minimize the risk of hemorrhage in the event of a major complication during
      transcatheter aortic valve implantation. BACKGROUND: Vascular access management
      is a major challenge in transfemoral TAVI due to the large introducer sheathes
      required. METHODS: Fifty-two pts underwent TAVI between November 2007 and March
      2009. Of these, 37 received an Edwards-Sapien Valve (23 mm valve: 17/37; 26 mm
      valve: 20/37) whilst 15 patients received a CoreValve (26 mm valve: 6/15; 29 mm
      valve: 9/15). Using a crossover technique, the opposing femoral artery was
      cannulated with a 7Fr long sheath. This allowed contralateral passage of a
      balloon and inflation in the proximal iliac. The sheath was then removed and
      Prostar sutures tied in a dry field. Balloon optimization of the puncture site
      was performed as required. RESULTS: In three subjects, elective surgical repair
      was undertaken due to excessive femoral arterial calcification. In the remaining
      49, the crossover technique was employed and closed with two Prostar devices
      (Edwards-Sapien) or one (CoreValve). There were serious "on-table" complications
      in seven patients, six due to the large introducer sheathes used in the TAVI
      procedure-iliac avulsion, two iliac dissections, iliac perforation, common
      femoral perforation and scrotal hematoma. All were repaired safely by combined
      surgical and endovascular techniques, using the crossover technique to ensure
      patient stability. All made a good recovery and were independently ambulant at
      discharge. CONCLUSION: Using crossover balloon inflation as an adjunct to Prostar
      closure may be helpful for managing TAVI vascular access sites.

PMID- 20049971
TI  - Mechanical versus pharmacologic support for cardiogenic shock.
AB  - Dynamic left ventricular outflow tract obstruction is a rare cause of cardiogenic
      shock after an acute myocardial infarction. A case is presented where inotropic
      support and an intra-aortic balloon pump aggravated the cardiac hemodynamics by
      this mechanism. The circulatory support provided by Impella 2.5 heart pump, in
      addition to discontinuation of inotropic support and intra-aortic balloon pump,
      allowed stabilization and successful percutaneous revascularization.

PMID- 20049972
TI  - A VCD robust mode analysis of induced chirality: the case of pulegone in
      chloroform.
AB  - Vibrational modes in an achiral molecule may acquire rotational strength by
      complexation to a chiral molecule, as happens for achiral solvent molecules
      complexed to a chiral solute. We investigate this transfer of chirality in
      vibrational circular dichroism for the pulegone molecule in CDCl(3) solvent from
      the point of view of the robustness concept introduced recently. It turns out
      that the transfer of chirality yields nonrobust modes, which means that, although
      they are observed in vibrational circular dichroism (VCD) experiments, the sign
      of these modes cannot be predicted reliably with standard (Density Functional
      Theory) VCD calculations. This limits the usefulness of the induced chirality
      phenomenon for obtaining information on the intermolecular interactions that give
      rise to it.

PMID- 20049973
TI  - Should fine-needle aspiration cytology be the first choice diagnostic modality
      for assessment of all nonpalpable breast lesions? The experience of a breast
      cancer screening center in Alexandria, Egypt.
AB  - Fine-needle aspiration cytology (FNAC) of breast masses has been replaced by
      ultrasound-guided core-needle biopsy (USG-CNB) in many countries. However, in
      Egypt, breast FNAC continues to play the major role in diagnosing breast masses.
      In this prospective study, we evaluated the efficacy of USG-FNACs performed at a
      breast cancer screening center by comparing the FNAC results with the
      corresponding definitive histological examination outcome. We also investigated
      the role that CNB can play as a complementary diagnostic tool for FNAC in
      selected cases. A total of 229 consecutive nonpalpable breast masses were
      included in this study. Each FNAC was placed into one of four categories: 3.5%
      nondiagnostic, 13.5% benign, 12.3% atypical/suspicious (indeterminate), and 70.7%
      malignant. The overall diagnostic accuracy was 98.9%, with a specificity and
      sensitivity of 99.3 and 96.7%, respectively. The overall positive predictive
      values and negative predictive values were 99.3 and 96.7%, respectively. Only 37
      masses (16%) were converted to CNB, with the indeterminate cytology being the
      most common cause (54%) for this conversion. Two cases demonstrating the superior
      benefit of FNAC over CNB are illustrated. Although we started the study by
      reserving CNB as a first choice to assess microcalcifications without
      architectural distortion, we ended the study by deciding to perform combined FNAC
      and CNB for this type of lesions. In conclusion, aiming to maximize the
      preoperative diagnosis of cancer, it would be cost efficient and time saving to
      use FNAC as a first-line investigation to benefit from the wealth of cytological
      information yielded, followed by CNB in selected cases.

PMID- 20049974
TI  - Metastatic peritoneal mesothelioma in the setting of recurrent ascites: a case
      report.
AB  - Malignant peritoneal mesothelioma is uncommon but rapidly fatal with a median
      survival of less than 1 year. The diagnosis of this entity is often delayed
      because of the nonspecific presenting symptoms and nonspecific cytological
      features of the mesothelial cells in the peritoneal fluids. A 72-year-old man who
      had no known history of exposure to asbestos and had longstanding refractory
      ascites thought to be secondary to alcoholic cirrhosis was found to have
      widespread metastatic malignant mesothelioma involving the lung, liver, pancreas,
      peritoneal, and pelvic wall, skin and subcutaneous tissue.

PMID- 20049975
TI  - Asteroid bodies in lymph node cytology: infrequently seen and still mysterious.
AB  - Granulomatous inflammation is a relatively common finding in routine aspiration
      cytology of lymph nodes. However, asteroid bodies are very rarely encountered in
      cytologic preparations, and most morphologic descriptions result from
      observations made in histologic tissue sections. This brief report describes the
      cytologic findings in paratracheal aspirate smears from a 74-year-old Caucasian
      woman with the history of squamous-cell carcinoma of the right ankle metastatic
      to a right groin lymph node. At the time of removal of the metastatic tumor, the
      patient was noted to have multiple small, mildly FDG-avid lymph nodes in the
      supraclavicular, paratracheal, precarinal, pulmonic hilar, and axillary regions.
      A transbronchial fine-needle aspiration biopsy (FNAB) of a paratracheal lymph
      node showed granulomatous inflammation and numerous multinucleated giant cells
      containing asteroid bodies. No evidence of malignancy was present in any of the
      smears. Additional patient history elicited at the time of FNAB revealed a
      diagnosis 6 years previously of disseminated histoplasmosis infection. A
      concomitant workup for sarcoidosis was negative.

PMID- 20049976
TI  - Emergent percutaneous coronary intervention for resuscitated victims of out-of
      hospital cardiac arrest.
AB  - Long-term survival rates even after successful resuscitation from out-of-hospital
      cardiac arrest are dismal. Most of those initially resuscitated expired during
      their hospitalization. Recent reports have suggested that a more aggressive
      approach to postresuscitation care is the key to better outcome. Waiting for the
      evidence of neurological recovery before acting can result in missed opportunity
      to improve such recovery. Immediate induction of mild therapeutic hypothermia for
      all resuscitated victims who remain comatose offers the best hope for
      neurological recovery. Numerous reports suggest that early coronary angiography
      and PCI also improve outcome among those resuscitated from cardiac arrest whose
      postresuscitation ECG show evidence of ST elevation myocardial infarctions. Most
      promising is combining these two postresuscitation therapies, namely immediate
      induction of hypothermia and early coronary angiography and PCI. Combining these
      therapies has resulted in long-term survival rates of 70% with more than 80% of
      all such survivors neurologically functional. Even those without ST elevation on
      their postresuscitation ECG can greatly benefit from timely induction of
      hypothermia and early angiography/PCI.

PMID- 20049977
TI  - Novel chiroptical analysis of hemoglobin by surface enhanced resonance Raman
      optical activity spectroscopy.
AB  - The metalloprotein hemoglobin (Hb) was studied using surface enhanced resonance
      Raman spectroscopy (SERRS) and surface enhanced resonance Raman optical activity
      (SERROA). The SERROA results are analyzed and compared with the SERRS, and the
      later to the resonance Raman (RRS) performed on Hb. The SERRS measurements
      careful optimization, with respect to the concentration and volume ratio of the
      analyte to colloids, enables for the first time SERROA of this molecule. We
      observed that the most intense SERROA signals were attributed the nu(4), nu(20),
      and nu(21) vibrations, which are sensitive to the redox state of the heme's iron
      ion, and to the presence of its sixth site, bound to exogenous ligand; O(2), NO
      or CO. However, in this study, the SERROA signals corresponding to these
      vibrations appear more sensitive to the Hb oxygen-binding properties than they
      appear in the SERRS or RRS. Moreover, the SERROA signal of Hb has successfully
      been monitored as a function of time, and was observed to be stable for 4-5 min.
      To our knowledge, the SERROA results of Hb, and its comparison to SERRS and RRS,
      are here reported for the first time.

PMID- 20049978
TI  - Reed-Sternberg cells in breast FNA of a patient with left breast mass.
AB  - Hodgkin's lymphoma is a potentially curable malignancy of the lymphatic system
      characterized by a variable number of scattered and large mononucleated and
      multinucleated tumor cells, the Hodgkin and Reed-Sternberg cells residing in an
      abundant heterogeneous admixture of non-neoplastic inflammatory cells. It
      represents approximately 30% of all lymphomas according to the World Health
      Organization (WHO). Patients with Hodgkin's lymphoma typically present with
      painless peripheral adenopathy, fever, night sweats, and weight loss. We report a
      rare case of Hodgkin's lymphoma presented as a breast mass in a 23-year-old woman
      diagnosed on fine needle aspiration (FNA). At presentation, she had no B
      symptoms, or palpable lymphadenopathy.

PMID- 20049979
TI  - KRAS mutation analysis on cytological specimens of metastatic colo-rectal cancer.
AB  - Recent evidences showed that metastatic colorectal cancer (CRC) patients with
      tumors harboring a KRAS gene mutation do not derive benefit from the
      administration of epidermal growth factor receptor-directed monoclonal
      antibodies. Typically, the specimens available for KRAS mutational analysis are
      formalin-fixed paraffin-embedded (FFPE) primary tumor tissue blocks. However, in
      patients with rectal tumours undergoing neoadjuvant therapy, the source of FFPE
      material is limited. In this setting, CRC cytological samples taken from the
      metastatic site may be exploited. However, these specimens show at least some
      degree of necrosis; thus, their suitability for the KRAS assay needs to be
      tested. Here, we show that 18/19 (94.7%) metastatic CRC smears were perfectly
      adequate for codon 12 and 13 KRAS mutational analysis by direct gene sequencing.
      Only one case (5.3%) showing abundant necrotic debris and poor cellular
      preservation was not informative for KRAS status. Codon 12 gene mutations were
      found in 4/18 (22.2%) of the adequate cases (c35G>T n = 2; c34G>T n = 1; c35G>A n
      = 1). Concordance between cytological and FFPE samples, both available in 13
      patients, occurred in 92.3% (12/13) of the cases. Thus, whenever histological
      specimens of CRC are notavailable, KRAS testing may be reliably performed on
      cytological specimens.

PMID- 20049980
TI  - Geographic distribution of autism in California: a retrospective birth cohort
      analysis.
AB  - Prenatal environmental exposures are among the risk factors being explored for
      associations with autism. We applied a new procedure combining multiple scan
      cluster detection tests to identify geographically defined areas of increased
      autism incidence. This procedure can serve as a first hypothesis-generating step
      aimed at localized environmental exposures, but would not be useful for assessing
      widely distributed exposures, such as household products, nor for exposures from
      nonpoint sources, such as traffic. Geocoded mothers' residences on 2,453,717
      California birth records, 1996-2000, were analyzed including 9,900 autism cases
      recorded in the California Department of Developmental Services (DDS) database
      through February 2006 which were matched to their corresponding birth records. We
      analyzed each of the 21 DDS Regional Center (RC) catchment areas separately
      because of the wide variation in diagnostic practices. Ten clusters of increased
      autism risk were identified in eight RC regions, and one Potential Cluster in
      each of two other RC regions.After determination of clusters, multiple mixed
      Poisson regression models were fit to assess differences in known demographic
      autism risk factors between the births within and outside areas of elevated
      autism incidence, independent of case status.Adjusted for other covariates, the
      majority of areas of autism clustering were characterized by high parental
      education, e.g. relative risks >4 for college-graduate vs. nonhigh-school
      graduate parents. This geographic association possibly occurs because RCs do not
      actively conduct case finding and parents with lower education are, for various
      reasons, less likely to successfully seek services.

PMID- 20049982
TI  - Civilization diseases and their relations with nutrition and the lifestyle.

PMID- 20049981
TI  - Expectant management of spontaneous first-trimester miscarriage: prospective
      validation of the '2-week rule'.
AB  - OBJECTIVES: To assess uptake and success of expectant management of first
      trimester miscarriage for a finite 14-day period, in order to evaluate our '2
      week rule' of management. METHODS: This was a prospective observational study
      evaluating our proposed 2-week rule of expectant management, which is based on
      the finding that women managed expectantly are most likely to miscarry in the
      first 14 days and that to wait longer than 2 weeks without intervention does not
      confer a greater chance of successful resolution. Eligible women diagnosed with
      first-trimester miscarriage were offered a choice of expectant management or
      surgical evacuation under general anesthesia. Inclusion criteria for expectant
      management were: diagnosis of incomplete miscarriage (heterogeneous tissue, with
      or without a gestational sac, seen on ultrasound in the uterine cavity and
      distorting the endometrial midline echo), missed miscarriage (crown-rump length
      (CRL) >or= 6 mm with absent fetal heart activity) or empty sac (anembryonic
      pregnancy) based on transvaginal ultrasonography. Women with complete
      miscarriage, missed miscarriage at the nuchal translucency scan, molar pregnancy
      or miscarriage >or= 3 weeks in duration (missed miscarriage in which the CRL was
      >or= 3 weeks smaller than the gestational age based on last menstrual period), or
      with signs of infection or hemodynamic instability were excluded. Expectant
      management consisted of weekly ultrasonography for 2 weeks. If after 2 weeks
      resolution was not complete, surgery was advised. RESULTS: 1062 consecutive
      pregnant women underwent transvaginal ultrasound examination. Of these, 38.6%
      (410/1062) were diagnosed with miscarriage, of whom 241 (59%) were symptomatic at
      the time of presentation and 282 were eligible for the study. These were offered
      expectant management and 80% (227/282) took up this option. 11% (24/227) were
      lost to follow-up; therefore, complete data were available on 203 women. Overall
      spontaneous resolution of miscarriage at 2 weeks was observed in 61% (124/203) of
      women. Rates of spontaneous resolution at 2 weeks according to the type of
      miscarriage were 71% for incomplete miscarriage, 53% for empty sac and 35% for
      missed miscarriage. The incidence of unplanned emergency dilatation and curettage
      due to gynecological infection or hemorrhage was 2.5% (5/203). CONCLUSIONS:
      Expectant management based on the 2-week rule is a viable and safe option for
      women with first-trimester miscarriage. Women with an incomplete miscarriage are
      apparently the most suitable for expectant management.

PMID- 20049983
TI  - Proceedings of the International Research Symposium on Ankyloblepharon-Ectodermal
      Defects-Cleft Lip/Palate (AEC) Syndrome, November 8-10, 2006, Houston, Texas,
      USA.

PMID- 20049984
TI  - Effect of polyamine-deficient chow on Trypanosoma brucei brucei infection in
      rats.
AB  - Polyamines are essential for proliferation of Trypanosoma brucei brucei, and
      feeding rats polyamine-deficient chow (PDC) decreases their blood polyamine
      concentrations. Proliferation of T. b. brucei (IL-tat 1.4 strain) (IL) is not
      restrained within PDC-fed rats. However, symptoms of IL-infected rats such as
      anemia decrease by PDC feeding. We reported cytokine and nitric oxide (NO)
      production of T. b. gambiense (Wellcome strain [WS])-infected rats were affected
      by PDC feeding, and WS proliferation was restrained. Therefore, we investigated
      whether the change in production of cytokines and NO by PDC feeding affects IL
      proliferation and decreases symptoms in vivo. In IL-infected PDC-fed rats, NO,
      interleukin (IL)-12, and tumor necrosis factor-alpha production increased while
      interferon-gamma and IL-10 decreased compared to normal chow-fed rats. IL
      proliferation was restrained by NO production when it was co-cultured with spleen
      cells harvested from uninfected rats. In contrast, IL proliferation in infected
      rats was not changed by PDC feeding, although NO production was increased. The
      results suggest that changes in cytokines and NO production in IL-infected rats
      by PDC feeding have little influence on IL proliferation. However, they may serve
      to decrease symptoms.

PMID- 20049985
TI  - Moderate Echinostoma trivolvis infection has no effects on physiology and fitness
      related traits of larval pickerel frogs (Rana palustris).
AB  - High intensity infections of Echinostoma trivolvis metacercariae decrease
      survival and growth of young amphibian larvae. However, in nature, parasites are
      highly aggregated, which results in a large proportion of the amphibian
      population being only moderately infected. Survival and growth responses at these
      more-common, low-infection levels remain poorly studied. Thus, we investigated
      the effects of moderate Echinostoma trivolvis metacercariae infection (following
      exposure to 0, 10, 30, or 90 cercariae) on the growth and development of pickerel
      frog (Rana palustris) tadpoles. We measured metabolism to determine whether
      increased energy expenditure is a potential physiological mechanism underlying
      previously documented reduced growth. Furthermore, we quantified tadpole
      intestine size, which can exhibit plasticity in response to changing metabolic
      demands, and we characterized metacercariae distribution in tadpole kidneys.
      Metacercariae encysted in the pronephros significantly more than in the
      mesonephros, but tended to occur equally in right and left kidneys. Two mo post
      infection (PI), there were no changes in tadpole survival, development, intestine
      size, or growth related to metacercariae infection. Similarly, metacercariae did
      not significantly increase metabolic rates during encystment or at 1 mo PI. Our
      study demonstrated that modest E. trivolvis infections, representative of a large
      proportion of the host population, had no detectable effects on fitness-related
      traits in laboratory isolation from other ecological variables.

PMID- 20049986
TI  - Development and ultrastructure of Cystoisospora canis Nemeseri, 1959 (syn,
      Isospora canis) monozoic cysts in two noncanine cell lines.
AB  - Cystoisospora canis is a coccidial parasite of the intestinal tract that can
      cause severe disease in dogs. Clinical signs include watery diarrhea, vomiting,
      fever, and weight loss. Extraintestinal stages of Cystoisospora spp. have been
      demonstrated in the mesenteric lymph nodes of paratenic hosts. Information on the
      biology of extraintestinal stages of canine Cystoisospora species is limited. The
      current study examined the development of C. canis in 2 noncanine cell lines and
      the ultrastructure of the monozoic cysts that formed. Monolayers of bovine
      turbinate cells and African green monkey kidney cells were grown on coverslips
      and inoculated with excysted C. canis sporozoites. Coverslips were collected on
      various days and fixed and stained for light microscopy (LM) or transmission
      electron microscopy (TEM). A single, centrally located, slightly crescent-shaped
      sporozoite surrounded by a thick cyst wall within a parasitophorous vacuole was
      observed with the use of LM and TEM. No division and no multinucleated stages
      were observed with either LM or TEM. With TEM, typical organelles of sporozoites
      were observed, such as rhoptries, dense granules, a crystalloid body,
      polysaccharide granules, and a conoid. The structure and ultrastructure of C.
      canis monozoic cysts produced in vitro are similar to extraintestinal cysts of
      other Cystoisospora species in experimentally infected animals and those of
      Cystoisospora belli observed in immunocompromised humans. This is the first study
      that fully demonstrates in vitro the development of what structurally resemble
      extraintestinal cysts of a Cystoisospora spp.

PMID- 20049987
TI  - Changes in gene expression in European eels (Anguilla anguilla) induced by
      infection with swim bladder nematodes (Anguillicola crassus).
AB  - The European eel, Anguilla anguilla, is considered an endangered species that is
      under pressure for many reasons. Among others, the introduced parasite
      Anguillicola crassus is thought to play an important role in the decline of eel
      populations. These nematodes have been shown to negatively affect many fitness
      related traits in eels, e.g., growth, osmoregulation, and stress tolerance.
      Nevertheless, there has been little work on the way in which the host-parasite
      interaction influences the molecular regulation of these key physiological
      processes. We experimentally analyzed the effect of this nematode on the
      expression of genes involved in the physiology of European eels during their
      continental life. Included are genes that are implicated in the eel's somatic
      growth (insulin-like growth factor 1 and thyroid hormone receptor beta),
      osmoregulation (Na+/K+-ATPase beta1 and aquaporin 3), and hematopoiesis
      (hemoglobin alpha-chain). Our results showed the absence of an effect on genes
      involved in fish growth; the parasite may, however, have an effect on
      osmoregulation and hematopoiesis. We also noted a differential impact of male and
      female parasites on the expression of some genes, perhaps owing to the sexual
      dimorphism in body size of the parasite.

PMID- 20049988
TI  - Seasonal dynamics of two mortality-related trematodes using an introduced snail.
AB  - Seasonal dynamics of 2 trematode species, Cyathocotyle bushiensis and
      Sphaeridiotrema globulus, were assessed in relation to life history traits of the
      parasites and their hosts, as well as abundance of host species and abundance of
      infective stages. Both of these trematodes are associated with recurrent
      mortality of migrating waterbirds on the Upper Mississippi River National
      Wildlife and Fish Refuge. An invasive snail species, Bithynia tentaculata, serves
      as intermediate host for both trematode species. In total, 2,970 snails were
      collected at 2 study sites. Prevalence and mean abundance of the 2 trematode
      species varied among dates and was attributed to several factors, including
      migration patterns of definitive hosts, snail population dynamics, and seasonal
      changes in temperature. The surge of new infections of both parasites seems to be
      due to avian hosts foraging at this site during spring migration. The high
      prevalence and abundance of metacercariae among the snail population promote
      mortality among molluscivorous birds by increasing the probability of ingestion
      of a lethal dose. Additionally, mortality of non-molluscivorous birds can be
      explained by accidental ingestion of a couple of highly infected snails resulting
      in a lethal dose.

PMID- 20049989
TI  - Predicted geographic ranges for North American sylvatic Trichinella species.
AB  - Because of a lack of comprehensive surveys, the geographic distributions of the
      North American species of encapsulating Trichinella (T. nativa and its variant
      T6, T. murrelli, and T. spiralis) are poorly characterized in detail. These
      species are potentially zoonotic; therefore, biogeographic information is
      critical to monitoring their status and any distribution changes due to climatic
      and man-made environmental impacts. The maximum entropy (Maxent) program was used
      to model predicted ranges for these sylvatic Trichinella spp., using a limited
      number of available location records with confirmed species identifications
      collected over 55 yr throughout North America. The resulting prediction models
      were shown to be robust, and the species maps created are presented. The
      predicted range of T. nativa is primarily north of the 48 degrees - 52 degrees
      latitudes, overlapping the Tundra, sub-Arctic, and Warm Continental eco-regions.
      Its sympatric genotypic variant, T6, has a predicted range covering primarily the
      sub-Arctic and mountainous Temperate Steppe eco-regions, the latter extending
      below 48 degrees N latitude. In the east, the T6 range includes the Warm
      Continental and the mountainous Hot Continental eco-regions; the T6 range is also
      predicted to extend to the Sierra Madre Mountains of Mexico. The most probable
      range of T. murrelli is centered in the Midwest within the Hot Continental and
      Prairie eco-regions, with an extension southward to the Subtropical and
      Tropical/Subtropical Steppe and Desert eco-regions. In the west, it exists in a
      restricted range characterized as mountainous Mediterranean. The most probable
      distribution of sylvatic T. spiralis is along the humid east North American coast
      (Hot Continental south to Subtropical), and along the coast of northwest North
      America (Marine) to Alaska (subArctic and Tundra). Its most southerly range
      extends into central Mexico (Tropical/Subtropical Desert). The difference in
      relative freeze resistance between T. nativa/T6 and T. murrelli undoubtedly
      accounts for much of this geographic separation. However, the factors responsible
      for the absence of a more southerly distribution of T. nativa are not obvious,
      given the overlap in host range with T. murrelli. The maximum July temperature
      appears to have a significant effect on this distribution pattern. The results of
      the model building highlight subjects for future research on the biotic and
      abiotic factors important in determining Trichinella spp. distributions and
      directions for model validation research.

PMID- 20049990
TI  - Chronology and development of juvenile bluegill parasite communities.
AB  - This study describes the parasite communities of juvenile bluegill and examines
      the development of parasite communities in juvenile bluegill from 2 Michigan
      lakes. Parasitological examination of 510 juvenile bluegill from 2 Michigan lakes
      (Three Lakes II [TL] and Gull Lake [GL]) demonstrated that TL bluegill harbored
      19 parasite species and GL bluegill harbored 16 parasite species. Parasite
      communities of juvenile bluegill from both lakes were dominated by larval
      parasites, particularly larval trematodes. A nonmetric multidimensional scaling
      analysis showed bluegill of similar lengths to have similar parasite communities.
      Relative influences of species richness on parasite infracommunities of juvenile
      bluegill suggest similar patterns of parasite community structure between TL and
      GL. Patterns in parasite colonization evident in both lakes suggest that the
      smallest juvenile bluegill are primarily vulnerable to colonization by parasites
      acquired through direct contact, particularly larval trematodes, while the
      majority of parasites acquired through ingestion are not acquired until juvenile
      bluegill are larger and less-gape limited.

PMID- 20049991
TI  - Morphological and molecular taxonomy of a new species of Fundulotrema and
      comments on Gyrodactylus stephanus (Monogenea: Gyrodactylidae) from Fundulus
      heteroclitus (Actinopterygii: Cyprinodontiformes) in Nova Scotia, Canada.
AB  - Fundulotrema porterensis n. sp. (Monogenea: Gyrodactylidae) is described from the
      mummichog, Fundulus heteroclitus (L.; Cyprinodontidae), inhabiting Porters Lake,
      Nova Scotia, Canada. The new parasite species is characterized by having a
      ventral bar with small anterolateral processes and linguiform membrane,
      differentiating it from all other known species of Fundulotrema. The
      morphological description of F. porterensis is supplemented with 1011 sequenced
      base pairs (bp) of ribosomal DNA (rDNA) spanning both internal transcribed
      spacers (ITS-1 and ITS-2) and 5.8S regions of the genome. A BLAST (basic local
      alignment search tool) search revealed that the 5.8S (157 bp) region varied by 1
      bp from Gyrodactylus turnbulli Harris, 1986 and G. pictae Cable, Oosterhout,
      Barson and Harris, 2005, which also infect cyprinodontids. Morphometrically, F.
      porterensis most closely resembles Fundulotremafoxi (Rawson, 1973), but the 2
      species are easily separated by length of hamuli (50.7 vs. 42.2 microm,
      respectively), length of anterolateral process of the ventral bar (4.9 vs. 8.9
      microm), shape of marginal hooks, and shape of the ventral bar membrane. A
      morphological and molecular supplemental diagnosis of Gyrodactylus stephanus
      Mueller, 1937, from the mummichog, is also presented. This new material provides
      previously unrecorded information on the attributes of the ventral bar, marginal
      hooks, and also clarifies the structure of the male copulatory organ (MCO).

PMID- 20049992
TI  - Polystomoides magdalenensis n. sp. (Monogenoidea: Polystomatidae), a parasite of
      buccal cavity of Trachemys callirostris callirostris (Testudinata: Emydidae) from
      Colombia.
AB  - Polystomoides magdalenensis n. sp. is described from the buccal cavity of the
      Colombian slider Trachemys callirostris callirostris (Gray, 1856) in the middle
      of Magdalena River drainage, Colombia. The new species is characterized by a
      combination of traits, i.e., 29-35 genital spines, outer and inner hamuli length
      (123-150 and 54-63, respectively), testis size (261.4-554.5 x 388.2-768.4),
      marginal hook lengths (45-51), and pharynx length (150-333), as well as testis
      length/oral sucker length, testis length/pharynx length, and testis width/pharynx
      width ratios. This is the first species described from turtles in Colombia and
      the fifth reported in chelonians from South America.

PMID- 20049993
TI  - Genomic analysis of Eimeria spp. populations in relation to performance levels of
      broiler chicken farms in Arkansas and North Carolina.
AB  - The impact of coccidiosis outbreaks on the productivity of broiler chicken farms
      can be substantial, depending on the severity of disease caused by particular
      species and strains of Eimeria. We examined the genetic diversity of Eimeria
      species present in commercial broiler farms in relation to their performance
      level. Four groups of broiler chicken farms in Arkansas (AR) and North Carolina
      (NC), having either high or low performance levels, were sampled for Eimeria spp.
      oocysts. We amplified gDNA from oocysts by using genus-specific primers targeting
      18S ribosomal RNA, the first and second internal transcribed spacer regions, and
      cytochrome c oxidase subunit I as the established species-specific primers.
      Eimeria spp. diversity was not homogenous among the 4 farm groups, with less
      pathogenic species (E. mitis and E. mivati-like) associated with AR and NC high
      performance farms, respectively, and a pathogenic species (E. brunetti)
      associated with AR low-performance farms. Sequence analyses identified multiple
      E. maxima and E. mitis genetic variants, from which 2 E. maxima variants were
      unique to low-performance farms. Distinct populations of sequences at the NC high
      performance farms were identified as E. mivati-like, based on homology searches.
      Our study demonstrated the utility of analyzing multiple genomic loci to assess
      composition and polymorphisms of Eimeria spp. populations.

PMID- 20049994
TI  - Analysis of Schistosoma mansoni population structure using total fecal egg
      sampling.
AB  - Many parasite populations are difficult to sample because they are not uniformly
      distributed between several host species and are often not easily collected from
      the living host, thereby limiting sample size and possibly distorting the
      representation of the population. For the parasite Schistosoma mansoni, we
      investigated the use of eggs, in aggregate, from the stools of infected
      individuals as a simple and representative sample. Previously, we demonstrated
      that microsatellite allele frequencies can be accurately estimated from pooled
      DNA of cloned S. mansoni adults. Here, we show that genotyping of parasite
      populations from reproductively isolated laboratory strains can be used to
      identify these specific populations based on characteristic patterns of allele
      frequencies, as observed by polyacrylamide gel electrophoresis and automated
      sequencer analysis of fluorescently labeled PCR products. Microsatellites used to
      genotype aggregates of eggs collected from stools of infected individuals
      produced results consistent with the geographic distribution of the samples.
      Preferential amplification of smaller alleles, and stutter PCR products, had
      negligible effect on measurement of genetic differentiation. Direct analysis of
      total stool eggs can be an important approach to questions of population genetics
      for this parasite by increasing the sample size to thousands per infected
      individual and by reducing bias.

PMID- 20049995
TI  - Development of an in vitro assay to examine intracellular survival of Perkinsus
      marinus trophozoites upon phagocytosis by oyster (Crassostrea virginica and
      Crassostrea ariakensis) hemocytes.
AB  - Perkinsus marinus is a facultative intracellular parasite that causes "Dermo"
      disease in the eastern oyster Crassostrea virginica. Although hemocytes from
      healthy oysters rapidly phagocytize P. marinus trophozoites, they fail to
      efficiently kill them. Instead, trophozoites survive and proliferate, eventually
      overwhelming the host. Because Chesapeake Bay oyster populations have been
      reduced to unprecedented levels, the introduction of the Suminoe oyster,
      Crassostrea ariakensis (synonymous C. rivularis), has recently been proposed.
      Although this species is refractory to developing Dermo disease, it can be
      infected by Perkinsus spp. and, thus, the mechanistic basis of its disease
      resistance remains intriguing. To examine whether the resistance to develop Dermo
      is due to a high capacity of C ariakensis hemocytes to kill internalized P.
      marinus, we developed an in vitro assay to compare intracellular survival and
      proliferation of P. marinus in C. virginica and C ariakensis hemocytes. Our
      results revealed that P. marinus cultured trophozoites have a similar capacity
      for in vitro survival within hemocytes from both oyster species, suggesting that
      the resistance of C. ariakensis to develop Dermo disease is most likely due to
      reduced parasite pathogenicity for the latter oyster species, rather than to
      infectivity. Together with the currently available P. marinus genome, EST
      sequences, and the transfection methodology we recently developed, this assay
      should significantly contribute to a rigorous identification of the P. marinus
      genes responsible for its intrahemocytic survival.

PMID- 20049996
TI  - In vitro cultivation of Microphallus turgidus (Trematoda: Microphallidae) from
      metacercaria to ovigerous adult with continuation of the life cycle in the
      laboratory.
AB  - In vitro cultivation of trematodes would aid studies on the basic biology of the
      parasites and the development of chemotherapies and vaccines. Our goal was to
      measure the in vitro survival and maturation of metacercariae of Microphallus
      turgidus under different culture conditions. Metacercariae of M. turgidus from
      grass shrimp (Palaemonetes pugio) were excysted and cultured in humidified air at
      37 degrees C in RPMI-1640 medium supplemented with 20% calf, chicken, or horse
      serum. Deposition of eggs was greatest in media containing horse or calf serum.
      Worms survived longest at 37 C, but did not produce greater numbers of eggs than
      worms cultured in RPMI-1640-supplemented horse serum at 42 degrees C. Most eggs
      deposited in vitro (>80%) were normal in shape and, after incubation for 10 days
      at 30 degrees C in brackish water, approximately 30% of them contained miracidia.
      Eighteen percent of hydrobiid snails (Spurwinkia salsa) fed these eggs shed
      cercariae 5-6 wk later. The cercariae were infective to grass shrimp
      (Palaemonetes vulgaris) and developed into metacercariae. This study is
      significant because it is the second instance in which a digenean, and the first
      time that a microphallid, has been demonstrated to develop in vitro from
      metacercariae into adult worms capable of producing infective eggs.

PMID- 20049997
TI  - New species of Pseudabbreviata (Nematoda: Physalopteridae) and other helminths in
      two species of Hypsilurus (Sauria: Agamidae) from Papua New Guinea.
AB  - Pseudabbreviata novaeguineaensis n. sp. from the stomach of Hypsilurus modestus
      (Agamidae) from Papua New Guinea is described and illustrated. The new species
      was also found in the stomach of Hypsilurus papuensis from Papua New Guinea.
      Pseudabbreviata novaeguineaensis n. sp. represents the sixth species assigned to
      the genus and the first from the Australo-Papuan Region. The new species differs
      from other species assigned to Pseudabbreviata by the vulva position in the
      female and pedunculate papillae arrangement in the male tail morphology. In
      addition to the new species, H. modestus harbored Meteterakis crombiei,
      Strongyluris gonyocephali, and larvae of Abbreviata sp. (in cysts).

PMID- 20049998
TI  - Erection of a new onchobothriid genus (Cestoda: Tetraphyllidea) and the
      description of five new species from whaler sharks (Carcharhinidae).
AB  - The onchobothriid Triloculatum n. gen. is erected to house species formerly
      considered members of Phoreiobothrium, but that bear 3, rather than 5 or more,
      bothridial subloculi. The species formerly known as Phoreiobothrium triloculatum
      is designated as its type. This species is redescribed based on 2 syntypes and on
      voucher material consistent with type material taken from the type host,
      Carcharhinus obscurus, from the type and 1 additional locality. Examination of
      the cestode fauna of a diversity of carcharhinid sharks resulted in the discovery
      of an additional 5 new tri-subloculate species belonging to the genus. These
      include: Triloculatum andersonorum n. sp. from Negaprion acutidens; Triloculatumr
      bullardi n. sp. from Carcharhinus brevipinna; Triloculatum geeceearelensis n. sp.
      from Carcharhinus isodon; Triloculatum jodyi n. sp. from Carcharhinus acronotus;
      and Triloculatum oregontwoae n. sp. from Carcharhinus plumbeus. The new species
      differ from one another in the number of proglottids, scolex size, number of
      testes, number of lateral columns of vitelline follicles, and whether they
      possess craspedote or acraspedote proglottids. Histology and scanning electron
      microscopy suggest that the new genus differs further from Phoreiobothrium in
      that its species possess an anterior margin of the posterior loculus that is
      fused to the anterior loculus, rather than free. The diagnosis of Phoreiobothrium
      is emended to accommodate the removal of tri-subloculate species and the new
      information on the condition of the locular interface, and the symmetrical ovary
      and vitelline follicles arranged in 2 lateral bands; each band consisting of 2 to
      many columns of follicles. Existing host data indicate that the new genus is
      restricted to only a subset of the sharks parasitized by species of
      Phoreiobothrium. Results from the examination of a diversity of carcharhinid
      species suggest that species in the new genus may have an affinity for the
      larger, i.e., >200 cm in total length, species of Carcharhinus and Negaprion. One
      of the new Triloculatum species was found to attach in the crypts lying between
      the larger ridges found on the mucosal surface of the posterior inner region of
      the scroll-type spiral intestine of C. brevipinna.

PMID- 20050000
TI  - Characterization of Dictyocaulus species (Nematoda: Trichostrongyloidea) from
      three species of wild ruminants in northwestern Spain.
AB  - Specimens of Dictyocaulus spp. were extracted from the respiratory tracts of 3
      ruminant hosts including roe deer (Capreolus capreolus), red deer (Cervus
      elaphus), and chamois (Rupicapra rupicapra) from wild populations in the province
      of Le6n, northwestern Spain. The near-complete nuclear small-subunit ribosomal
      RNA gene, and 2 regions of the large-subunit ribosomal RNA gene, were amplified
      by PCR and sequenced. The SSU rDNA gene sequences indicated a high level of
      similarity between the isolate from C elaphus and the published sequences for
      Dictyocaulus eckerti. SSU rDNA gene sequences were identical in the isolates from
      C. capreolus and R. rupicapra, and both corresponded to published sequences for
      D. capreolus. The LSU rDNA gene sequences differed in isolates from the latter 2
      hosts, indicating the possible presence of an undescribed Dictyocaulus sp. in R.
      rupicapra. These results showed that the LSU rDNA gene sequences are useful
      indicators of genetic and species diversity in species of Dictyocaulus.

PMID- 20050001
TI  - A new dicyemid from Opisthoteuthis depressa (Mollusca: Cephalopoda: Octopoda).
AB  - A new species of dicyemid mesozoan is described from Opisthoteuthis depressa
      Iijima and Ikeda, 1895, collected from Suruga Bay in Japan. Dicyemennea
      umbraculum n. sp. is a medium species that reaches approximately 3500 microm in
      length. This species attaches to the surface of the renal appendages. The
      vermiform stages are characterized as having 22 or 23 peripheral cells, a disc
      shaped calotte, and an axial cell that extends to the propolar cells. An anterior
      abortive axial cell is absent in vermiform embryos. Infusoriform embryos consist
      of 37 cells; a single nucleus is present in each urn cell, and the refringent
      bodies are solid. This is the first description of a dicyemid from
      Opisthoteuthis.

PMID- 20049999
TI  - Molecular systematics of the avian schistosome genus Trichobilharzia (Trematoda:
      Schistosomatidae) in North America.
AB  - Trichobilharzia is a genus of threadlike schistosomes with a cosmopolitan
      distribution in birds. Species of Trichobilharzia achieve notoriety as major
      etiological agents of cercarial dermatitis, or swimmer's itch. There are 40
      species described in the literature, for which the majority lacks molecular
      sequence information. To better understand the phylogenetic relationships,
      diversity, species boundaries, host use, and geographic distribution of this
      genus better, we surveyed 378 birds and over 10,000 snails from North America.
      The phylogenetic analysis was based on nuclear 18S, 28S rDNA, internal
      transcribed spacer region and mitochondrial cytochrome oxidase I sequence data.
      Specimens were recovered that could be related to 6 of the 14 described species
      of Trichobilharzia from North America (Trichobilharzia physellae, Trichobilharzia
      querquedulae, Trichobilharzia szidati, Trichobilharzia stagnicolae,
      Trichobilharzia franki, and Trichobilharzia brantae). An additional 5 lineages
      were found that could not be related directly to previously described species.
      Trichobilharzia brantae, transmitted by Gyraulus parvus, grouped outside the
      clade containing the recognized species of Trichobilharzia. A subgroup of the
      Trichobilharzia clade designated Clade Q was comprised of closely related species
      whose adults and eggs are similar, yet the European species use lymnaeids whereas
      the North American species use physids as snail hosts. This molecular phylogeny
      provides a useful framework (1) to facilitate identification of worms, including
      those involved in dermatitis outbreaks; (2) to test hypotheses about the
      evolution, diversification, host-parasite interactions and character evolution of
      Trichobilharzia; and (3) to guide future taxonomic revision of Trichobilharzia.

PMID- 20050002
TI  - A new Encephalitozoon species (Microsporidia) isolated from the lubber
      grasshopper, Romalea microptera (Beauvois) (Orthoptera: Romaleidae).
AB  - We describe a new microsporidian species, Encephalitozoon romaleae n. sp.,
      isolated from an invertebrate host, the grasshopper Romalea microptera, collected
      near Weeks Island, Louisiana, and Jacksonville, Florida. This microsporidian is
      characterized by specificity to the gastric caecae and midgut tissues of the host
      and a life cycle that is nearly identical to that of Encephalitozoon hellem and
      Encephalitozoon cuniculi. Mature spores are larger (3.97 x 1.95 microm) than
      those of other Encephalitozoon species. Polar filament coils number 7 to 8 in a
      single row. Analysis of the small subunit (SSU) rDNA shows that E. romaleae fits
      well into the Encephalitozoon group and is a sister taxon to E. hellem. This is
      the first Encephalitozoon species that has been shown to complete its life cycle
      in an invertebrate host.

PMID- 20050003
TI  - New species of Freitascapillaria (Nematoda: Capillariidae) from the intestine of
      Cottus caeruleomentum (Teleostei: Cottidae) in Maryland.
AB  - A new species of capillariid nematode, Freitascapillaria laticauda n. sp.
      (Capillariidae), is described from the intestine of the blue ridge sculpin,
      Cottus caeruleomentum (Cottidae, Scorpaeniformes) from the Blue Lick Run,
      Maryland, United States. It differs from its congeners mainly in the body length
      (male 3.1-5.4 mm, female 7.0-11.1 mm), the length of the male esophagus (1.5-2.9
      mm) and spicule (42-45 microm), and the size of eggs (60-66 x 27-33 microm).
      Previous records of Freitascapillaria spp. were from characid, poeciliid, and
      cyprinid fishes in Brazil, Neotropical Mexico, and China, respectively, so that
      F. laticauda n. sp. is the first species of this genus reported from Nearctic
      North America and from a scorpaeniform fish.

PMID- 20050004
TI  - Two new species of Eimeria (Apicomplexa: Eimeriidae) from eastern red bats,
      Lasiurus borealis (Chiroptera: Vespertilionidae), in Arkansas and North Carolina.
AB  - During August 2003 and August 2004, 11 adult eastern red bats, Lasiurus borealis,
      were collected and their feces examined for coccidian parasites. Bats were
      obtained in August 2003 from Garland, Montgomery, and Yell counties, Arkansas
      (n=6) and in August 2004 from Anson and Montgomery counties, North Carolina
      (n=5). Seven (63.6%) of the bats were passing oocysts of 2 undescribed species of
      Eimeria. Oocysts of Eimeria dowleri n. sp. were subspherical to ellipsoidal, 24.7
      x 22.0 (23-26 x 20-23) microm, with a bilayered wall, externally moderately
      pitted, internally smooth, and with a shape index of 1.1. Micropyle and oocyst
      residuum were absent, but a polar granule was present. Sporocysts were ovoidal,
      13.4 x 9.2 (12-14 x 8-9) pm; shape index was 1.5; Stieda and sub-Stieda bodies
      were present. A sporocyst residuum consisting of homogeneous granules was
      scattered among the sporozoites; sporozoites were elongate, with a subspherical
      anterior refractile body and an elongate posterior refractile body; a nucleus was
      not discernable. Oocysts of Eimeria sealanderi n. sp. were subspherical to
      ellipsoidal, 16.7 x 14.4 (15-18 x 13-16) microm, with a bilayered wall,
      externally lightly pitted, internally smooth, and with a shape index of 1.2. A
      micropyle was absent, but the oocyst residuum and polar granule were present.
      Oocyst residuum consisted of a single, membrane-bound homogenous granule.
      Sporocysts were ovoidal, 8.9 x 5.7 (8-10 x 5-6) microm, with a shape index of
      1.6; Stieda and sub-Stieda bodies were present. The sporocyst residuum consisted
      of 10, to several dozen, homogeneous granules of various sizes loosely clustered
      among the sporozoites, which were elongate and without obvious refractile bodies
      and nucleus. This is the first time any coccidian has been reported from this
      host and the first instance of a bat coccidian reported from North Carolina.

PMID- 20050005
TI  - A new species of tetraphyllidean (Cestoda) from the Largespot River stingray,
      Potamotrygon falkneri (Potamotrygonidae: Chondrichthyes), from the Parana basin.
AB  - Rhinebothrium paranaensis n. sp. (Tetraphyllidea: Cestoda) is described from the
      freshwater stingray Potamotrygon falkneri collected in the Colastine River, a
      tributary to the Lower Parana River in Argentina. The specimens were studied in
      detail using light and scanning electron microscopy and histology. Rhinebothrium
      paranaensis can be distinguished from all valid species in the genus using the
      following combination of characters: worm length, number of proglottids, diamond
      shaped bothridia lacking constriction, number of loculi on the distal surface of
      bothridium, and the lack of vaginal sphincter and external seminal vesicle.

PMID- 20050006
TI  - Azithromycin reduces ocular infection during congenital transmission of
      toxoplasmosis in the Calomys callosus model.
AB  - Toxoplasma gondii is a widely distributed obligatory intracellular parasite that
      causes severe disease to the fetus when transmitted during pregnancy. Drugs used
      to avoid congenital transmission have shown side effects, and their efficacy is
      controversial. The most widely used treatment for acute toxoplasmosis during
      pregnancy is pyrimethamine plus sulfadiazine, which has several side effects. In
      this work, we tested the efficacy of azithromycin in reducing congenital
      transmission of T. gondii in the large vesper mouse, Calomys callosus, a rodent.
      Females of C callosus were inoculated perorally with 20 cysts of ME49 strain of
      T. gondii on the day of fertilization, and fetuses were collected from the 15th
      to the 19th day of gestation. Azithromycin (300 mg/kg), in association with
      pyrimethamine (100 or 50 mg/kg) plus sulfadiazine (100 or 75 mg/kg) and folinic
      acid (15 mg/kg) (SPAf), or vehicle, were administered orally on different days
      after infection. Brain and ocular tissues were removed and processed for
      immunohistochemistry using a polyclonal antibody against T. gondii, or were
      processed for parasite DNA quantification. Toxoplasma gondii was detected in the
      brains of all females and in fetuses' eyes of C. callosus treated with SPAf. On
      the other hand, in females treated with azithromycin, there was a reduction of T.
      gondii in the brains of mothers, and no parasites were detected in eyes of
      fetuses, indicating that azithromycin may represent an alternative treatment for
      toxoplasmosis during pregnancy.

PMID- 20050007
TI  - Helminths parasitizing Columbina picui (Columbiformes: Columbidae) in Brazil.
AB  - Columbina picui (picui ground-dove) is a small, diurnal columbid bird that lives,
      in couples or flocks, in open areas in the countryside and urban centers. The
      species occurs in Brazil and other countries in South America. The aim of this
      study was to identify the helminths that parasitize C. picui in the state of Rio
      Grande do Sul, southern Brazil. Thirty-four specimens were necropsied; in each
      case, the organs were isolated and examined separately. The nematodes and their
      prevalences were: Ascaridia columbae (26.5%) and Ornithostrongylus iheringi
      (11.8%) in the small intestine; Dispharynx nasuta in the proventriculus (5.9%)
      and gizzard (2.9%); and a Dispharynx sp. (2.9%) in the proventriculus. This is
      the first report of D. nasuta parasitizing C. picui in Brazil and the first
      record of A. columbae and O. iheringi infecting C. picui in the state of Rio
      Grande do Sul, Brazil.

PMID- 20050008
TI  - Helminth parasites from the stomach of conger eel, Conger conger, from Madeira
      Island, Atlantic Ocean.
AB  - Geographic variations in the diversity and prevalence of helminth parasites of
      fish can provide important clues as to the relatedness of fish populations. In
      the present work, the stomachs of 64 conger eels, Conger conger, collected during
      1999 and 2000, were examined for the presence of parasites. Four fish were
      infected with L3 stages of the nematode Anisakis simplex s.l. (Anisakidae), 1
      with the nematode Cristitectus congeri (Cystidicolidae), 1 with the
      acanthocephalan Rhadinorhynchus pristis, 17 with postlarvae of Sphyriocephalus
      tergestinus (Eucestoda: Trypanorhyncha), and 55 with Lecithochirium spp.
      (Digenea: Hemiuridae). The hemiurids were the most abundant parasites, with a
      total of 385 individuals recovered. Strong aggregated distributions were found
      for both the digeneans, Lecithochirium musculus and Lecithochirium fusiforme,
      with variance-to-mean ratios (s2/x) and index of discrepancy (D) 13.98 and 0.672
      (for L. musculus) and 8.08 and 0.90 for L. fusiforme, respectively. Intensity of
      L. musculus, L. fusiforme, and S. tergestinus showed significant relationships
      with depth of capture. Differences in number of species and prevalence were found
      between Madeira and the Atlantic coasts of the Iberian Peninsula.

PMID- 20050009
TI  - Notes on population dynamics of Amblyomma ticks (Acari: Ixodidae) in Brazil.
AB  - Previous population dynamics data, generated for Amblyomma parvum Aragao and
      Amblyomma cajennense (Fabricius) in Argentina and southeastern Brazil, have
      indicated that these ticks complete 1 generation per year, with larvae
      predominating in autumn, nymphs in winter, and mostly adults during spring and
      summer. The present study reports population dynamics data for free-living
      Amblyomma spp. ticks in northern Brazil (Amazon forest, latitude 10 degrees S, 63
      degrees W), and for Amblyomma spp. ticks collected on birds in southeastern
      Brazil (latitude 23 degrees S, 45 degrees W). In northern Brazil, adult ticks
      predominated from mid-spring to mid-autumn, larvae predominated in early winter,
      and nymphs from mid-winter to mid-spring. Seven Amblyomma spp. were identified,
      although A. cajennense predominated in 1 of the 2 sites sampled. In southeastern
      Brazil, larval infestations on birds peaked in autumn, followed by a nymphal
      infestation peak in late winter. At least 32% and 75% of these larvae and nymphs,
      respectively, were identified as Amblyomma longirostre (Koch). Similar to
      previous work, the present study showed that Amblyomma spp. larvae and nymphs
      predominated during autumn-winter months, and mostly adults during spring-summer
      months, a pattern compatible with 1 generation/yr, even at latitude 10 degrees S
      in northern Brazil.

PMID- 20050010
TI  - Long-term survival of Toxoplasma gondii sporulated oocysts in seawater.
AB  - Toxoplasma gondii is now recognized as an important pathogen in costal marine
      mammals. Oocysts from cat feces are believed to be washed into seawater and serve
      as a source of infection via transport hosts. Experimentally, it has been
      demonstrated that T. gondii oocysts can sporulate in seawater and remain
      infectious for mice for up to 6 mo. The present study examined the long-term
      survival of T. gondii in seawater (15 ppt NaCl) kept at 4 C or at room
      temperature. Oocysts kept at 4 C for 24 mo were orally infectious for mice, while
      those kept at room temperature for 24 mo were not.

PMID- 20050011
TI  - Trypanosoma cf. varani in an imported ball python (Python reginus) from Ghana.
AB  - Peripheral blood from a ball python (Python reginus) imported from Ghana was
      cultured in Barbour-Stoenner-Kelly (BSK) medium for Borrelia spp. isolation,
      resulting in the prominent appearance of free, and clusters of, trypanosomes in a
      variety of morphological forms. The molecular phylogenetic characterization of
      these cultured trypanosomes, using the small subunit rDNA, indicated that this
      python was infected with a species closely related to Trypanosoma varani Wenyon,
      1908, originally described in the Nile monitor lizard (Varanus niloticus) from
      Sudan. Furthermore, nucleotide sequences of glycosomal glyceraldehyde-3-phosphate
      dehydrogenase gene of both isolates showed few differences. Giemsa-stained blood
      smears, prepared from the infected python 8 mo after the initial observation of
      trypanosomes in hemoculture, contained trypomastigotes with a broad body and a
      short, free flagellum; these most closely resembled the original description of
      T. varani, or T. voltariae Macfie, 1919 recorded in a black-necked spitting cobra
      (Naja nigricollis) from Ghana. It is highly possible that lizards and snakes
      could naturally share an identical trypanosome species. Alternatively, lizards
      and snakes in the same region might have closely related, but distinct,
      Trypanosoma species as a result of sympatric speciation. From multiple
      viewpoints, including molecular phylogenetic analyses, reappraisal of trypanosome
      species from a wide range of reptiles in Africa is needed to clarify the
      relationship of recorded species, or to unmask unrecorded species.

PMID- 20050012
TI  - Evidence-based practice to outcomes management: spiraled learning activities,
      Part IV.

PMID- 20050013
TI  - Association between Mediterranean Diet and late-life cognition.

PMID- 20050014
TI  - Words of wisdom. Re: Active surveillance for the management of prostate cancer in
      a contemporary cohort. Dall'Era MA, Konety BR, Cowan JE, Shinohara K, Stauf F,
      Cooperberg MR, Meng MV, Kane CJ, Perez N, Master VA, Carroll PR. Cancer
      2008;112:2664-70.

PMID- 20050015
TI  - Words of wisdom. Re: Timing of androgen deprivation therapy and its impact on
      survival after radical prostatectomy: a matched cohort study. Siddiqui SA,
      Boorjian SA, Inman B, Bagniewski S, Bergstralh EJ, Blute ML. J Urol 2008;179:1830
      7; discussion 1837.

PMID- 20050016
TI  - Words of wisdom. Re: Prostate cancer-specific survival following salvage
      radiotherapy versus observation in men with biochemical recurrence after radical
      prostatectomy. Trock BJ, Han M, Freedland SJ, Humphreys EB, DeWeese TL, Partin
      AW, Walsh PC. JAMA 2008;299:2760-9.

PMID- 20050017
TI  - Words of wisdom. Re: Phase I clinical trial of a selective inhibitor of CYP17,
      abiraterone acetate, confirms that castration-resistant prostate cancer commonly
      remains hormone driven. Attard G, Reide AHM, Yap TA, Raynaud F, Dowsett M,
      Settatree S, Barrett M, Parker C, Martins V, Folkerd E, Clark J, Cooper C, Kaye
      S, Dearnaley D, Lee G, de Bono JS. J Clin Oncol 2008;26:4563-71.

PMID- 20050018
TI  - Words of wisdom. Re: Weight loss with a low-carbohydrate, Mediterranean, or low
      fat diet. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I,
      Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B,
      Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM,
      Bluher M, Stumvoll M, Stampfer MJ. Dietary Intervention Randomized Controlled
      Trial (DIRECT) Group. N Engl J Med 2008;359:229-41.

PMID- 20050019
TI  - Words of wisdom. Re: Temsirolimus, interferon alfa, or both for advanced renal
      cell carcinoma. Hudes G, Carducci M, Tomczak P, Dutcher J, Figlin R, Kapoor A,
      Staroslawska E, Sosman J, McDermott D, Bodrogi I, Kovacevic Z, Lesovoy V, Schmidt
      Wolf IG, Barbarash O, Gokmen E, O'Toole T, Lustgarten S, Moore L, Motzer RJ;
      Global ARCC Trial. N Engl J Med 2007;356:2271-81.

PMID- 20050020
TI  - Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged
      human skin.
AB  - Skin hair follicles (HF) contain bulge stem cells (SC) that regenerate HFs during
      hair cycles, and repair skin epithelia following injury. As natural aging is
      associated with decreased skin repair capacity in humans, we have investigated
      the impact of age on human scalp HF bulge cell number and function. Here, we
      isolated human bulge cells, characterized as CD200+/KRT15+/KRT19+ cells of the
      HF, by dissection-combined CD200 selection in young and aged human skin. Targeted
      transcriptional profiling indicates that KRT15, KRT19, Dkk3, Dkk4, Tcf3, S100A4,
      Gas1, EGFR and CTGF/CCN2 are also preferentially expressed by human bulge cells,
      compared to differentiated HF keratinocytes (KC). Our results demonstrate that
      aging does not alter expression or localization of these HF SC markers. In
      addition, we could not detect significant differences in HF density or bulge cell
      number between young and aged human scalp skin. Interestingly, hedgehog (Hh)
      signaling is activated in human bulge cells in vivo, and down-regulated in
      differentiated HF KCs, both in young and aged skin. In addition, activation of Hh
      signaling by lentivirus-mediated overexpression of transcription factor Gli1
      induces transcription of HF SC markers KRT15, KRT19, and Gas1, in cultured KCs.
      Together with previously reported knock-out mouse results, these data suggest a
      role for Hh signaling in maintaining bulge cell phenotype in young and aged human
      skin.

PMID- 20050021
TI  - A little respect, please.

PMID- 20050022
TI  - Spreading the word.

PMID- 20050023
TI  - Calling attention to vaccination technique.

PMID- 20050024
TI  - Conservative management usually first call.

PMID- 20050025
TI  - Perspectives on ecological risk assessment of chiral compounds.
AB  - Enantiomers of chiral contaminants can significantly differ in environmental fate
      as well as in effects. Despite this fact, such differences are often ignored in
      regulation and in practice, injecting uncertainty into the estimation of risk of
      chiral compounds. We review the unique challenges posed by stereochemistry to the
      ecological risk assessment of chiral contaminants and existing regulatory
      guidance for chiral pharmaceuticals and pesticides in the United States. We
      identify the advantages of obtaining data on fate and effects of each individual
      enantiomer of chiral contaminants that are either distributed as or may end up as
      enantiomer mixtures in the environment due to enantiomerization. Because
      enantiomers of the same compound are highly likely to coexist in the environment
      with each other and can result in nonadditive effects, we recommend treatment of
      enantiomers as components of a mixture using widely accepted mixture models from
      achiral risk assessment. We further propose the enantiomer hazard ratio for
      retrospectively characterizing relative enantiomer risk and examine uncertainty
      factor magnitudes for effects analysis.

PMID- 20050026
TI  - A new concept for the environmental risk assessment of poorly water soluble
      compounds and its application to consumer products.
AB  - Many consumer products contain lipophilic, poorly soluble ingredients
      representing large-volume substances whose aquatic toxicity cannot be adequately
      determined with standard methods for a number of reasons. In such cases, a
      recently developed approach can be used to define an aquatic exposure threshold
      of no concern (ETNCaq; i.e., a concentration below which no adverse affects on
      the environment are to be expected). A risk assessment can be performed by
      comparing the ETNCaq value with the aquatic exposure levels of poorly soluble
      substances. Accordingly, the aquatic exposure levels of substances with water
      solubility below the ETNCaq will not exceed the ecotoxicological no-effect
      concentration; therefore, their risk can be assessed as being negligible. The
      ETNCaq value relevant for substances with a narcotic mode of action is 1.9
      microg/L. To apply the above risk assessment strategy, the solubility in water
      needs to be known. Most frequently, this parameter is estimated by means of
      quantitative structure/activity relationships based on the log octanol-water
      partition coefficient (log Kow). The predictive value of several calculation
      models for water solubility has been investigated by this method with the use of
      more recent experimental solubility data for lipophilic compounds. A linear
      regression model was shown to be the most suitable for providing correct
      predictions without underestimation of real water solubility. To define a log Kow
      threshold suitable for reliably predicting a water solubility of less than 1.9
      microg/L, a confidence limit was established by statistical comparison of the
      experimental solubility data with their log Kow. It was found that a threshold of
      log Kow = 7 generally allows discrimination between substances with solubility
      greater than and less than 1.9 microg/L. Accordingly, organic substances with a
      baseline toxicity and log Kow > 7 do not require further testing to prove that
      they have low environmental risk. In applying this concept, the uncertainty of
      the prediction of water solubility can be accounted for. If the predicted
      solubility in water is to be below ETNCaq with a probability of 95%, the
      corresponding log Kow value is 8.

PMID- 20050027
TI  - Ecological risks of an old wood impregnation mill: application of the Triad
      approach.
AB  - Although many studies deal with the distribution and mobility of chromated copper
      arsenate (CCA) metals in soil, the ecotoxicity of CCA-contaminated soils is
      rarely studied. The Triad approach was applied to determine the ecological risks
      posed by a CCA mixture at a decommissioned wood impregnation mill in southern
      Finland. A combination of (1) chemical analyses; (2) toxicity tests with plants
      (aquatic: Lemna minor; terrestrial: Lactuca sativa), earthworms (Lumbricus
      rubellus), and enchytraeids (Enchytraeus albidus) conducted on contaminated
      soils, their aqueous extracts, and well water collected from the site; and (3)
      determination of the abundance of enchytraeids and nematodes and the
      bioaccumulation of metals in plants (horsetail) collected from the field were
      used to assess the actual risk. Although metal concentrations were low, L. minor
      growth appeared to be reduced by As contamination of the well water. In soil,
      metals were heterogeneously distributed with total concentrations of 14.8 to 4360
      mg As/kg, 15.2 to 1740 mg Cr/kg, and 4.83 to 790 mg Cu/kg. In several samples,
      concentrations were above Finnish regulatory guideline values and exceeded the
      half maximal effective concentration (EC50) or 50% lethal concentration (LC50)
      values for the toxicity of the individual metals to earthworms and enchytraeids,
      indicating hazards to the ecosystem. (Bio)availability of metals was high, as
      indicated by weak electrolyte extractions and body residues in L. rubellus and E.
      albidus exposed in bioassays. Earthworm survival correlated significantly with
      body metal concentrations, but not with soil total metal concentrations.
      Enchytraeid responses in the soil bioassays were less sensitive to CCA metal
      exposure. Plant growth was affected by CCA pollution, with L. sativa root
      elongation correlating significantly with total and available As concentrations
      and L. minor development being significantly reduced in H2O extracts of the most
      contaminated soil sample. Abundance of enchytraeids and nematodes in the field
      was much lower than in nonpolluted Finnish soils but did not significantly
      correlate with CCA contamination. Arsenic accumulation in horsetail did not
      correlate with As concentrations in soil. Overall, the results of the 3 lines of
      evidence of the Triad approach indicate possible increased risks to the ecosystem
      at the most contaminated sites of the CCA treatment area.

PMID- 20050028
TI  - Multidisciplinary life cycle metrics and tools for green buildings.
AB  - Building sector stakeholders need compelling metrics, tools, data, and case
      studies to support major investments in sustainable technologies. Proponents of
      green building widely claim that buildings integrating sustainable technologies
      are cost effective, but often these claims are based on incomplete, anecdotal
      evidence that is difficult to reproduce and defend. The claims suffer from 2 main
      weaknesses: 1) buildings on which claims are based are not necessarily "green" in
      a science-based, life cycle assessment (LCA) sense and 2) measures of cost
      effectiveness often are not based on standard methods for measuring economic
      worth. Yet, the building industry demands compelling metrics to justify
      sustainable building designs. The problem is hard to solve because, until now,
      neither methods nor robust data supporting defensible business cases were
      available. The US National Institute of Standards and Technology (NIST) Building
      and Fire Research Laboratory is beginning to address these needs by developing
      metrics and tools for assessing the life cycle economic and environmental
      performance of buildings. Economic performance is measured with the use of
      standard life cycle costing methods. Environmental performance is measured by LCA
      methods that assess the "carbon footprint" of buildings, as well as 11 other
      sustainability metrics, including fossil fuel depletion, smog formation, water
      use, habitat alteration, indoor air quality, and effects on human health. Carbon
      efficiency ratios and other eco-efficiency metrics are established to yield
      science-based measures of the relative worth, or "business cases," for green
      buildings. Here, the approach is illustrated through a realistic building case
      study focused on different heating, ventilation, air conditioning technology
      energy efficiency. Additionally, the evolution of the Building for Environmental
      and Economic Sustainability multidisciplinary team and future plans in this area
      are described.

PMID- 20050029
TI  - Ecosystem impairment evaluation on biodiversity and functional diversity for
      contaminated soil assessment.
AB  - A site-specific ecological risk assessment procedure for a qualitative evaluation
      of impairment occurring at the ecosystem level, as a result of soil
      contamination, was developed to integrate and visualize impairment in both
      terrestrial biodiversity and functional diversity and to support the decision
      maker in the contaminated site assessment. An Ecosystem Impairment Matrix (EcoIM)
      was proposed to identify the relationships between the applied measurement
      endpoints and the taxonomic groups living in the terrestrial system and between
      these taxonomic groups and the fundamental ecological processes. A specific
      impairment analysis procedure that used expert judgment allowed for the linking
      of impairment highlighted by the measurement endpoints with the terrestrial
      ecosystem's structure and functionality. Impairment occurring on each ecological
      element (i.e., biodiversity aspects and ecological functions and processes) was
      visualized by colored cells--1 for each relationship among measurement endpoint,
      taxonomic group, and ecological element--to support the expert in the ecosystem
      impairment evaluation. These results were then reported by the expert into the
      Global Ecosystem Impairment Evaluation Matrix (GEM) to summarize the obtained
      information and formulate a final judgment on ecosystem quality status. EcoIM and
      GEM were implemented in Module 2 of the decision support system DSS-ERAMANIA and
      are presented in this paper. The tools have been preliminarily applied to the
      Acna di Cengio (Italy) contaminated site; the results of this application are
      also presented and discussed.

PMID- 20050030
TI  - Sensitivity analysis of pesticides contaminating groundwater by applying
      probability and transport methods.
AB  - The use of pesticides is a potential threat to local groundwater. Once
      groundwater is contaminated, it is very difficult to clean. Thus, it is of
      importance to assess the risk of contaminating local groundwater at an early
      stage when pesticides are found in soils. This knowledge will also help in
      remediation strategies. Traditional methods of deterministic analysis cannot
      explicitly account for the sometimes large uncertainties that exist at this stage
      in the work, whereas probabilistic analyses are better suited for dealing with
      these problems. In this paper, we have combined contaminant transport with a 1st
      order reliability approach. Pesticide concentrations in soil have been studied to
      estimate the probability of failure--that is, of pesticides exceeding established
      critical levels in groundwater. Results indict that failure probability increases
      rapidly within a certain range of pesticide concentrations in soil for different
      critical levels. In given aquifer conditions and contaminants, probabilities of
      contaminants exceeding particular critical levels can easily be obtained
      according to various water usage scenarios. The distribution of importance
      factors among variables indicates the contribution their relative weights make to
      the failure probability. Hence, authorities can easily form sensitivity factors
      to take action and reduce the risk of contaminating the groundwater.

PMID- 20050031
TI  - Polychlorinated biphenyls and Hudson River white perch: implications for
      population-level ecological risk assessment and risk management.
AB  - Risk assessments and risk management decisions concerning risks to wild fish
      populations resulting from exposures to polychlorinated biphenyls (PCBs) and
      related chemicals have been based primarily on observations of effects of
      chemicals on individual organisms. Although the development and application of
      population-level ecological risk-assessment methods is proceeding at a rapid
      pace, the organism-level approach is still being justified by arguments that
      population-level ecological risk assessment is in an early stage of development
      and has not been shown to be reliable. This article highlights the importance of
      including population-level effects in risk-management decision-making, by
      examining the effects of exposures to PCBs on fish populations inhabiting the
      Hudson River, New York, USA, a system in which data have been collected for
      approximately 30 y concerning both concentrations of PCBs in sediment and fish
      tissue and the abundance and reproduction of exposed fish populations. We
      previously tested hypotheses concerning the effects of PCBs on the striped bass
      population of the Hudson River, and found that the available data conflicted with
      all of these hypotheses. Here, we report results of similar analyses of effects
      of historic PCB exposures on the Hudson River white perch population, using an
      extended data set that recently became available. As with striped bass, we found
      no correlation between maternal PCB tissue concentrations and any measure of
      reproductive success in Hudson River white perch during the 30-y period covered
      by the data set. Together with results of studies performed on fish populations
      exposed to PCBs at other sites, our results clearly demonstrate that
      physiological and genetic adaptation, biological compensation, and other
      ecological processes influence responses of fish populations to PCB exposures and
      should be considered in risk management decision-making.

PMID- 20050032
TI  - Application of life cycle thinking in multidisciplinary multistakeholder contexts
      for cross-sectoral planning and implementation of sustainable development
      projects.
AB  - Development planning and implementation is a multifaceted and multiscale task
      mainly because of the involvement of multiple stakeholders across sectors and
      disciplines. Even though top-down sectoral planning is commonly practiced, bottom
      up cross-sectoral planning involving all relevant stakeholders in a
      transdisciplinary learning environment has been recognized as a better option,
      especially if the goal is to drive development projects toward sustainable
      implementation (Rowe and Fudge 2003; Muller et al. 2005; Global Development
      Research Center 2008). Even though many planning approaches have this goal, there
      are limited decision frameworks that are suitable for achieving consensus among
      stakeholders from multiple disciplines with sectoral objectives and priorities.
      In most instances, the upstream and downstream effects of development decisions
      are not thoroughly investigated or communicated with the relevant stakeholders,
      strongly affecting cross-sectoral integration in the real world (Wiek, Brundiers,
      et al. 2006). This article presents methodological aspects of developing a
      stakeholder based life cycle assessment framework (SBLCA) for upstream-downstream
      decision analysis in a multistakeholder development planning context. The
      applicability of the framework is demonstrated using simple examples extracted
      from a pilot case study conducted in Sri Lanka for sustainable posttsunami
      reconstruction at a village scale. The applicability of SBLCA in specific
      planning stages, how it promotes transdisciplinary learning and cross-sectoral
      stakeholder integration in phases of project cycles, and how local stakeholders
      can practice life cycle thinking in their village development planning and
      implementation are discussed.

PMID- 20050033
TI  - The need for adequate quality assurance/quality control measures for selenium
      larval deformity assessments: implications for tissue residue guidelines.
AB  - Assessing the frequency and severity of larval fish deformities is a subjective
      exercise that is subject to considerable parameter uncertainty unless appropriate
      quality assurance/quality control (QA/QC) measures are incorporated. This issue
      has received limited attention in the literature. Only one study was identified
      that contained adequate data to evaluate the reproducibility of larval deformity
      data. Parameter uncertainty was substantially larger than expected. There was
      poor reproducibility between observers for nearly all types and magnitudes of
      deformities, and there were particularly large differences in how mild
      deformities were assessed. The reproducibility of the edema endpoint was the
      poorest of the 4 types of deformity evaluated. Specific recommendations for
      improving the QA/QC aspects of larval deformity assessments include blind and
      nonsequential labeling; explicit effort on the development and application of an
      a priori framework; internal QC checks to quantify the influence of sample
      preservatives, observer drift, or multiple observers; and an external QC check of
      a minimum of 10% of all larval fish. Future selenium reproductive studies should
      include an explicit uncertainty analysis and disclose raw deformity data to
      facilitate recalculation of tissue residue guidelines as the science in this area
      advances.

PMID- 20050034
TI  - Pesticide risk management using indicators for vineyards in the central valley of
      Chile.
AB  - The Apalta catchment is a wine-producing area of 1300 ha, lying south of
      Santiago, located in the Colchagua Valley, near Santa Cruz in the VI Region of
      Chile. The vineyards are planted on slopes of up to 22 degrees, the rows being
      aligned mainly down the slope. This cropping system and its management lead to a
      potential contamination of natural resources. To assess the risk of environmental
      contamination due to the application of pesticides in different pest control
      strategies, indicators at a field level were derived according to a step-by-step
      procedure. Using these indicators, runoff was found to be the main process of
      impact. The different pest control strategies in this catchment caused different
      potential risks, though these in general were low.

PMID- 20050035
TI  - Early decompressive hemicraniectomy in fulminant herpes simplex encephalitis.
AB  - Herpes encephalitis can be a life-threatening condition, despite early
      instauration of acyclovir treatment. In particular patients may succumb to
      rapidly progressive cerebral oedema. We report a 66-year patient with a Glasgow
      Coma Score (GCS) of 6 and incipient uncus herniation of the right temporal lobe
      on the third day. Decompressive hemicraniectomy was immediately performed. The
      long-term outcome was satisfactory with unassisted gait and a Barthel Index score
      of 70 after 9 months.

PMID- 20050036
TI  - Proceedings of the 6th Young Investigators' Symposium on Smooth Muscle. November
      6-9, 2007. Sydney, Australia.

PMID- 20050037
TI  - Brain function investigation by magnetic resonance, electrophysiology, and
      pharmaceutical probes, in combination. Proceedings of the International School on
      Magnetic Resonance and Brain Function 6th Workshop. May 18-25, 2008. Erice,
      Sicily, Italy.

PMID- 20050039
TI  - Preface to the molecular and polymer gels; materials with self-assembled
      fibrillar networks special issue.

PMID- 20050038
TI  - The safety and price of guns in Kentucky.

PMID- 20050040
TI  - Supramolecular hydrogel of a D-amino acid dipeptide for controlled drug release
      in vivo.
AB  - A supramolecular hydrogel based on D-amino acids, which resists hydrolysis
      catalyzed by proteinase K and offers long-term biostability, exhibits controlled
      release in vivo, as proved by the pharmacokinetics of encapsulated 125I tracers
      and the SPECT imaging of the hydrogel-encapsulated 131I tracers. As the first in
      vivo imaging investigation of the drug release properties of the supramolecular
      hydrogel, isotope encapsulation serves as a valid, useful assay for
      characterizing the controlled release properties of supramolecular hydrogels in
      vivo. Our results indicate that supramolecular hydrogels promise new biomaterials
      for controlled drug release.

PMID- 20050041
TI  - Azobenzene-based light-responsive hydrogel system.
AB  - A deoxycholic acid-modified beta-cyclodextrin derivative (2) and an azobenzene
      branched poly(acrylic acid) copolymer (3) were prepared, and the association and
      dissociation of 2 with the trans/cis-azobenzene units in 3 were characterized by
      UV/vis spectroscopy, induced circular dichroism, and 1H NMR spectroscopy. The
      experimental results indicate that the trans-azobenzene units are bound strongly
      within the cavities of 2 whereas the cis-azobenzene is not bound at all. A
      supramolecular inclusion complex (1), formed by 2 and 3, is accompanied by the
      formation of a hydrogel. The light-responsive gel-to-sol and sol-to-gel phase
      transitions of the hydrogel, induced by trans-cis photoisomerization of the
      azobenzene units, were investigated. In the hydrogel system, the trans-azobenzene
      units in 3 are included inside the hydrophobic cavity of 2. Upon photoirradiation
      with UV light of 355 nm, the hydrogel is converted efficiently to the sol phase
      because the trans-azobenzene units are converted photochemically to their cis
      configurations, whereupon the resulting cis-azobenzene units dissociate from 2.
      The hydrogel can be recovered from the sol phase by photoirradiation with visible
      light of 450 nm. The swelling ratio for fresh hydrogel samples, which was found
      to be 8.7 +/- 0.7, was measured for a number of gel-to-sol and sol-to-gel phase
      transition cycles.

PMID- 20050042
TI  - Metal ion and anion-based "tuning" of a supramolecular metallogel.
AB  - A bis(pyridylurea) ligand (1) forms metallogels in methanol in the presence of up
      to 0.5 equiv of copper(II) chloride. The metallogel has been characterized using
      powder X-ray diffraction, SEM, and MAS NMR spectroscopic techniques. The addition
      of further copper(II) chloride gives the unusual crystalline 4:3 coordination
      polymer [Cu3(1)4Cl4]Cl2 x nH2O (2). In the presence of 0.5 equiv of copper(II)
      nitrate, the 2:1 crystalline coordination polymer [Cu(1)2](NO3)2 x H2O x MeOH (5)
      is isolated. Both 2 and 5 have been characterized by single-crystal X-ray
      diffraction. Complex 5 represents a possible model for the gelator and highlights
      key interactions with counteranions that suggest a means to tune gel properties
      using anion binding. The influence of chloride and acetate anions (as their NBu4+
      salts) on the rheological properties of the copper(II) chloride metallogels of 1
      are investigated. The rheology of the anion-containing mixtures shows complex
      behavior with the gel structure apparently evolving over time.

PMID- 20050043
TI  - Two-component thermoreversible hydrogels of melamine and gallic acid.
AB  - A new two-component hydrogel of melamine and gallic acid is reported for three
      different compositions of the components. Optical and scanning electron
      microscopy indicate the fibrillar network structure of the gel, and the DSC study
      indicates a reversible first-order phase transition in the system. The storage
      modulus (G') versus frequency plot is linear and invariant at 35 and 50 degrees C
      but not at 70 degrees C, where it is in the sol state. The theological melting
      point of 58 degrees C is close to the gel melting point obtained from DSC. The
      system shows a strong influence of pH on gelation. An FTIR study indicates H-bond
      formation between the > C=O group of gallic acid and the -NH2 group of melamine.
      1H NMR spectra indicate the presence of pi-pi stacking in the gel. The UV-vis
      peak positions of gallic acid remain unaffected during complexation; however, the
      normalized absorption intensity is higher in the GM13 sol compared to that of
      other complexes. The photoluminescence (PL) spectra of the gels are interesting,
      showing a two-order increase in intensity in the gel state compared to that in
      the sol state. Three different structures of the complexes are proposed for the
      three different compositions of the components.

PMID- 20050044
TI  - Cyanobacterial megamolecule sacran efficiently forms LC gels with very heavy
      metal ions.
AB  - We extracted the megamolecular polysaccharide sacran, which contains carboxylate
      and sulfate groups, from the jellylike extracellular matrix (ECM) of the
      cyanobacterium Aphanothece sacrum, which has mineral adsorption bioactivity. We
      investigated the gelation properties of sacran binding with various heavy metal
      ions. The sacran chain adsorbed heavier metal ions such as indium, rare earth
      metals, and lead ions more efficiently to form gel beads. In addition, trivalent
      metal ions adsorbed onto the sacran chains more efficiently than did divalent
      ions. The investigation of the metal ion binding ratio on sacran chains
      demonstrated that sacran adsorbed gadolinium trivalent ions more efficiently than
      indium trivalent ions. Gel bead formation may be closely correlated to the liquid
      crystalline organization of sacran.

PMID- 20050045
TI  - Pyromellitamide gelators: exponential rate of aggregation, hierarchical assembly,
      and their viscoelastic response to anions.
AB  - The gelation and aggregation properties of a newly synthesized structurally
      simplified tetrahexyl pyromellitamide 2 have been studied and compared to the
      previously reported tetra(ethylhexanoate) pyromellitide 1, indicating that the
      ester groups in the latter significantly impede its aggregation. Morphology
      studies (AFM and TEM) on the aggregates formed by tetrahexyl pyromellitamide 2 in
      cyclohexane revealed highly uniform aggregates with different dimensions at
      different starting concentrations, suggesting that this molecule aggregates in a
      hierarchical fashion from a one-dimensional supramolecular polymer through hollow
      tubes or compressed helices to a network structure and then to a gel. This
      hypothesis is further supported by viscosity measurements that indicate a
      crossover point where individual supramolecular fibers get entangled at
      concentrations above ca. 3 mM in cyclohexane. Addition of 1 equiv of
      tetraalkylammonium salts of chloride or bromide, however, caused the viscosities
      of these pyromellitamide solutions to drop by a factor of 2-3 orders of
      magnitude, demonstrating the sensitivity of these aggregates to the presence of
      small anions. The sensitivity to anions does depend on the solubility of the
      salts used as small anion salts with little solubility in cyclohexane did not
      show this effect. Time-dependent viscosity studies showed that the aggregation of
      pyromellitamide 2 follows an exponential rate law, possibly related to the
      columnar rearrangements that are associated with the observed 6 angstroms
      contraction in d spacing in the XRD pattern of these gels. These results,
      particularly on the importance of kinetics of aggregation of self-assembled
      pyromellitamide gels, will be useful for future development of related materials
      for a number of applications, including tissue engineering and drug delivery.

PMID- 20050046
TI  - Poly(vinyl alcohol)-borate hydro/cosolvent gels: viscoelastic properties,
      solubilizing power, and application to art conservation.
AB  - We report the development of a new type of hydrogel in which a cosolvent has been
      added to the water component. The gel networks are based on the well-known
      poly(vinyl alcohol)-borate systems (PVA-borate). However, it is shown that the
      rheological and solubilizing properties of the hydrogels can be modified
      drastically by the addition of a cosolvent. The studies have focused on 1
      propanol as the added liquid, although it is shown that others (propylene
      carbonate, 1-pentanol, cyclohexanone, and 2-butanol) are amenable to making
      modified hydrogels as well. In addition to the rheological measurements, the gels
      have been investigated by differential scanning calorimetry (free water index)
      and determination of their solubilizing power. Finally, the gels have been
      applied to clean and oxidized varnish (patina) from the surface of a XVI-XVII
      century oil-on-wood painting by Ludovico Cardi detto il Cigoli. The mode of
      cleaning by and removal of the PVA-borate water/1-propanol gel from the painted
      surface demonstrate several advantages over other gels used in art conservation.

PMID- 20050047
TI  - Design and self-assembly of L-glutamate-based aromatic dendrons as ambidextrous
      gelators of water and organic solvents.
AB  - A series of L-glutamate-based dendrons containing aromatic cores ranging from
      phenyl to naphthyl to anthryl were synthesized, and their self-assembly in
      organic solvents as well as in water was investigated. It was found that all of
      these dendrons formed organogels with hexane and simultaneously formed the
      hydrogels with water, thus exhibiting ambidextrous properties. Nanofiber
      structures are essentially formed in organogels and hydrogels, and some
      nanostrips are formed in some of the hydrogels. During gel formation, both
      hydrogen bonds between the amide groups and the pi-pi stacking between the
      aromatic rings played a predominant role in forming the ID nanostructures. Both
      the hydrogels and the organogels containing naphthyl and anthryl groups showed
      fluorescence emission. In comparison with the corresponding compounds in
      solution, the naphthyl-containing dendrons showed a strong enhancement of
      fluorescence in the gel. In the case of anthryl-containing dendrons, fluorescence
      enhancement was observed for the derivative with anthryl substituted at the 9
      position, whereas a decrease was observed for the gels of the 2-substituted
      derivative. Although the chirality of L-glutamate could not be transferred to the
      aromatic chromophores in solution, it was transferred to the chromophores in gels
      as a result of the self-assembly and strong pi-pi interaction of the gelators. On
      the basis of the properties of the organogels and hydrogels, a thermally driven
      chiroptical switch was proposed. That is, the chirality disappeared when the gel
      was heated to solution, whereas it returned when cooled to a gel. The process can
      be repeated many times.

PMID- 20050049
TI  - Metathesis within self-assembled gels: transcribing nanostructured soft materials
      into a more robust form.
AB  - This article reports the covalent capture of self-assembled gel-phase materials
      using alkene metathesis. Gels assembled from a gelator functionalized with
      peripheral alkene groups were reacted with Grubbs' second generation catalyst,
      added as a solution to the top of the gel and allowed to diffuse into the
      material for 24 h. Using this approach, the fibrillar self-assembled network was
      covalently captured, yielding a large amount of insoluble material that was
      robust, thermally stable, and highly swellable in solvents compatible with the
      gelator. Scanning electron microscopy demonstrated that the insoluble
      metathesized material contained nanoscale fibers, which were aligned into rigid
      fiber bundles on drying. When the gelator was assembled in the presence of a
      second non-cross-linkable gelator, self-sorting took place, giving rise to two
      independent gelator networks. Metathesis then generated an insoluble material in
      which the individual gel fibers of the cross-linkable gelator were captured,
      whereas the nonreactive gelator could be washed away. Intriguingly, using this
      approach appeared to hinder the alignment of gel fibers into rigid fiber bundles.
      Instead, individual, well-defined, robust gelator nanofibers were visualized in
      the dried materials. In addition, the material synthesized this way appeared to
      be even more highly porous and swellable on the addition of solvent. In summary,
      this article demonstrates that metathesis is an effective way to capture
      nanostructured gel-phase materials covalently, with the judicious choice of
      additives helping to control the morphology and behavior of the materials
      generated. This approach to nanofabrication could ultimately give rise to
      nanostructured polymeric materials with a wide range of applications.

PMID- 20050048
TI  - Mapping the local osmotic modulus of polymer gels.
AB  - Polymer gels undergo volume phase transition in a thermodynamically poor solvent
      as a result of changes in molecular interactions. The osmotic pressure of gels,
      both synthetic and biological in nature, induces swelling and imparts the
      materials with the capacity to resist compressive loads. We have investigated the
      mechanical and swelling properties of poly(vinyl alcohol) (PVA) gels brought into
      the unstable state by changing the composition of the solvent. Chemically cross
      linked PVA gels were prepared and initially swollen in water at 25 degrees C, and
      then n-propyl alcohol (nonsolvent) was gradually added to the equilibrium liquid.
      AFM imaging and force-indentation measurements were made in water/n-propyl
      alcohol mixtures of different composition. It has been found that the elastic
      modulus of the gels exhibits simple scaling behavior as a function of the polymer
      concentration in each solvent mixture over the entire concentration range
      investigated. The power law exponent n obtained for the concentration dependence
      of the shear modulus increases from 2.3 (in pure water) to 7.4 (in 35% (v/v)
      water + 65% (v/v) n-propyl alcohol mixture). In the vicinity of the theta-solvent
      composition (59% (v/v) water + 41% (v/v) n-propyl alcohol) n approximately 2.9.
      Shear and osmotic modulus maps of the phase separating gels have been
      constructed. It is demonstrated that the latter sensitively reflects the changes
      both in the topography and thermodynamic interactions occurring in the course of
      volume phase transition.

PMID- 20050050
TI  - Lyomesophases of C3-symmetrical bipyridine-based discs in alkanes: an X-ray
      diffraction study.
AB  - The importance of the role of alkane solvents in the self-assembly process of pi
      conjugated molecules is well recognized but hardly understood. Here we present
      our results on the X-ray diffraction studies that we conducted to gain insight
      into the supramolecular structure of mixtures of a bipyridine-based molecule (1)
      with alkanes. Independent of the alkane used (linear or branched), above x(w) >
      0.06 (with x(w) being the weight fraction of 1) the mixtures show lyotropic
      liquid-crystalline behavior. The nature of the lyomesophase depends only on x(w)
      and not on the nature of the alkane (linear or branched). A columnar rectangular
      phase is present when x(w) > 0.66. Upon dilution of 1, a columnar hexagonal phase
      is assigned first (0.50 < x(w) < 0.65), and finally a columnar nematic phase is
      observed when x(w) < 0.50. Concentration-dependent SAXD measurements revealed
      that the dilution of 1 can be viewed as a swelling process. First, solvent
      molecules occupy space between the columns formed by 1, which are not disrupted.
      This process can quantitatively be described by a 2D swelling model. Only at
      lower concentrations does 3D swelling start as the columns start breaking into
      shorter fragments.

PMID- 20050051
TI  - Balancing hydrogen bonding and van der Waals interactions in cyclohexane-based
      bisamide and bisurea organogelators.
AB  - The solvent dependence of the gelation properties, the thermotropic behavior, and
      the melting enthalpy of a series of enantiomerically pure cyclohexane-based
      bisamide and bisurea compounds are reported. The two series of gelators examined
      are related structurally with the intermolecular interactions responsible for
      gelation differing in a systematic manner through varying the length of the alkyl
      tail and the number of hydrogen bonding units present. The gelation properties of
      the compounds in decalin, DMSO, and 1-propanol were studied by FTIR spectroscopy
      and by comparison of the thermal stability of their gels as determined by
      dropping ball experiments and by differential scanning calorimetry (DSC). FTIR
      spectroscopy, supported by the single-crystal X-ray diffraction of a3, indicates
      that the gelator molecules are aggregated through intermolecular hydrogen bonding
      in all of the solvents examined. The thermal stability of the gels in apolar and
      polar solvents was found to be dependent primarily on the relative strength of
      intermolecular hydrogen bonding and van der Waals interactions, respectively,
      compared with the strength of solvent-gelator interactions. The results of DSC
      indicated that the contribution of the difference in intergelator van der Waals
      interactions, compared with the gelator-solvent van der Waals and hydrogen
      bonding interactions, provided by the alkyl tail to the stability of the gel has
      a linear relationship with the number of methylene units in alkyl chains of
      length greater than six. In polar solvents, this contribution lies between 3.5
      and 4.2 kJ mol(-1) per methylene unit, and in apolar solvents, it is 2.2 kJ mol(
      1). The hydrogen bonding interactions were weaker in polar solvents and hence
      gelation occurred only where sufficient compensation was provided by intergelator
      van der Waals interactions. The results show that the direct relation of gelation
      strength to changes in solvent properties is not possible and more complex
      relationships should be considered. Furthermore, it is apparent that the
      development of design rules for the construction of LMWG molecules incorporating
      more than one anisotropic growth element must take into consideration the role of
      the solvent in determining which of the contributions is dominant.

PMID- 20050052
TI  - Vimentin intermediate filament formation: in vitro measurement and mathematical
      modeling of the filament length distribution during assembly.
AB  - The salt-induced in vitro assembly of cytoplasmic intermediate filament (IF)
      proteins such as vimentin is characterized by a very rapid lateral association of
      soluble tetrameric subunits into 60-nm-long full-width "unit-length" filaments
      (ULFs). We have demonstrated for this prototype IF protein that filament
      elongation occurs by the longitudinal annealing of ULFs into short IFs. These IFs
      further longitudinally anneal and thus constitute a progressively elongating
      filament population that over time yields filaments of several microm in length.
      Previously, we provided a mathematical model for the kinetics of the assembly
      process based on the average length distribution of filaments as determined by
      time-lapse electron and atomic force microscopy. Thereby, we were able to
      substantiate the concept that end-to-end-annealing of both ULFs and short
      filaments is obligatory for the formation of long IFs (Kirmse, R.; Portet, S.;
      Mucke, N. Aebi, U.; Herrmann, H.; Langowski, J. J. Biol. Chem. 2007, 282, 18563
      18572). As the next step in understanding the mechanics of IF formation, we have
      expanded our mathematical model to describe the quantitative aspects of IF
      assembly by taking into account geometry constraints as well as the diffusion
      properties of rodlike linear aggregates. Thereby, we have developed a robust
      model for the time-dependent filament length distribution of IFs under standard
      conditions.

PMID- 20050053
TI  - A new species of Anomiopsyllus Baker, 1904 (Insecta: Siphonaptera), and
      noteworthy records of fleas from Nelson's woodrat, Neotoma nelsoni (Rodentia:
      Cricetidae), in the Oriental Basin, Mexico.
AB  - We report the first record of ectoparasites from Nelson's woodrat, Neotoma
      nelsoni, a rare, endemic mammal of east-central Mexico. We also describe a new
      flea species of Anomiopsyllus (A. perontesis n. sp.), which presents a complete
      row of bristles on sternum IX and 3 blunt spines on movable process; provide a
      new country record for the flea Stenistomera alpina (Baker, 1985); and report a
      new host record for the flea Echidnophaga gallinacea (Westwood, 1875). A
      taxonomic key for the new species is included.

PMID- 20050054
TI  - [Organization of timely detection of pulmonary tuberculosis in an investigatory
      isolation ward].
AB  - The purpose of the study was to evaluate the efficiency of fluography (FLG) as a
      technique for the timely detection of cases of pulmonary tuberculosis in an
      investigatory isolation ward. According to the WHO data, at early detection
      stages the bacteria-discharging persons should constitute about 80% of all cases.
      Analysis of the first FLG films made in 22,973 prisoners in 2005-2007 revealed
      abnormalities in 7.6% of the convicts and tuberculosis-associated changes in 77%
      of cases. Sputum smear luminescence microscopy and culture for Mycobacterium
      tuberculosis in 115 patients showed that the persons who discharged bacteria were
      72.2% of the patients. The data suggest that FLG is highly effective in timely
      identifying cases of pulmonary tuberculosis.

PMID- 20050056
TI  - [Impact of information-and-education work with new cases of tuberculosis on
      therapeutic effectiveness].
AB  - The paper describes a procedure for information exposure of new cases of
      tuberculosis, which is based on the prediction of low treatment adherence, by
      using the diagnostic complex that is a scoring system for rating the sociomedical
      and psychological characteristics of patients, which determine the prediction of
      their treatment compliance. Group information work has been done with all
      patients; there has been individual work with risk-group patients to discontinue
      therapy. Comparative analysis of the results of treatment in 131 patients
      demonstrates that the information exposure system has assisted in significantly
      enhancing the patients' adherence to treatment and its efficiency.

PMID- 20050055
TI  - [Diaskintest for tuberculosis in children and adolescents].
AB  - To study whether Diaskintest might be used as a criterion for the activity of
      local tuberculous changes in children and adolescents, the authors examined three
      groups of patients aged 0 to 17 years: 1) 20 patients with new-onset tuberculosis
      in the progression phase; 2) 25 patients with new-onset tuberculosis in the
      regression phase with the signs of consolidation and calcification; 3) 18
      tuberculosis dispensary Group IIIB patients who received the basic course of
      therapy and had residual posttuberculous changes as calcinates and compact foci.
      Group 3 was found to greatly differ from Groups 1 and 2 in the lower rates of
      positive reactions, the higher rate of negative reactions, and smaller papulae
      while the Mantoux test with 2 TE indicated that in Group 3, the papulae were
      smaller than those in Group 2. Responses to the Diaskintest test versus the
      Mantoux 2TE test were significantly more pronounced in patients with progressive
      tuberculosis and less marked in dispensary Group IIB patients who received the
      basic course of antituberculous therapy. Diaskintest was ascertained to be used
      in the complex examination of children and adolescents as a criterion for the
      activity of tuberculous changes in order to choose the tactics of treatment and
      follow-up of children and adolescents. The application of Diaskintest will allow
      more objective formation of dispensary Group IIIA of children served by a local
      phthisiatrician.

PMID- 20050057
TI  - [Physical factors in human ecology and environmental hygiene].
AB  - The paper considers the problem while studying various physical factors of the
      environment. It presents prospects for further investigations of the influence of
      physical factors on human health and the quality of the environment. The paper
      also gives a detailed description of advances and promising lines of studies in
      the area under discussion.

PMID- 20050058
TI  - [Problem of safety provision of nanodimensional objects for human health].
AB  - Nanotechnologies are now considered to be a new industrial revolution. The areas
      of application of current nanomaterials are diverse and comprise electronics,
      chemical industry, building, medicine, and manufacture of foods and consumer
      goods. The unusual physicochemical properties of nanomaterials, which are
      determined by their high dispersity (particle sizes less than 100 nm in at least
      one dimension), may cause them to be able to penetrate across the biological
      barriers of the organism, to interact with biological macromolecules and cell
      structures, and to produce a toxic effect. Today it is recognized that studies of
      the potential toxic properties of nanoparticles and nanomaterials of artificial
      origin must be under way at a brisk pace. To determine the priorities of
      nanotoxicological studies, the authors have developed an algorithm that predicts
      a potential risk posed by nanodimensional objects to human health and the
      environment, by analyzing the safety of their physicochemical properties.

PMID- 20050059
TI  - [Evaluation of physical exposures of motor transport during hygienic examination
      of design materials to establish the size of a sanitary break].
AB  - The paper presents the results of assessing the conformity of building,
      reconstruction, and highway maintenance with the standards, by establishing the
      size of a sanitary break during examination of design materials in case of the
      Saint Petersburg ring road, the West high-speed diameter, E-18 Scandinavia,
      surface high-speed line passenger railway routes in Saint Petersburg, etc.

PMID- 20050060
TI  - [The loudness and hazard of noise; phenomenology, measurement, and evaluation].
AB  - The loudness and hazard of noise as a determinant of sound undesirability are
      considered. Physiological and hygienic acoustics are compared in the context of
      biomechanics and psychoacoustics. Evaluation of pulse noises and a problem of the
      diurnal action of noise on working and non-working populations are considered.
      Despite an abundance of acoustic indices, no uniform theory exists pertaining to
      the population's complaints. The European Union noise regulations, unsolved
      problems, their solution, and prospects are outlined.

PMID- 20050061
TI  - [Assessment of a risk from aviation noise exposure to the population's health].
AB  - The paper gives an algorithm, a procedure for calculation of aircraft noise, and
      its spread modeling. The performed investigations have provided guidelines that
      will become the first Russian official guiding document for assessing a risk from
      aviation noise to human health.

PMID- 20050062
TI  - [Experimental study of proflavine acetate phototransformation processes].
AB  - Changes in proflavine acetate phototransformation processes upon exposure to
      visible-range irradiation were studied by high performance liquid chromatography.
      Proflavine acetate was offered as a photosensitizer during photodynamic water
      disinfection. Dye transformation products upon time-varying exposure to
      irradiation were identified. By using structure-activity relationships and
      information from toxicity databases, the authors evaluated the hazard of the
      identified products and identified the most hazardous ones.

PMID- 20050063
TI  - [Patient radiation safety in the development of the medical standards "patient
      management protocols"].
AB  - The aim of the study was to develop a procedure for substantiating the control
      irradiation levels during medical irradiation. Two databases on the controlled
      parameters of R-equipment and on the individual patient doses from outpatient
      cards were analyzed.

PMID- 20050064
TI  - [Radionuclide indication of the relative economic ecological safety of local
      ecosystems].
AB  - The use of radioactive isotopes as indicators has been theoretically and
      experimentally substantiated for comparison of the ecological safety of local
      ecosystems. The higher concentration of cosmogeneous 7Be and the lower
      concentration of terrestrial 222Rn and its disintegration products in the
      environment are, the safer the total ecological situation is in the local
      ecosystem. Experimental and comparative data on the concentrations of 7Be in the
      surface air and grass in Moscow are given by the years and months of the early
      21st century. The results are assessed as a promising line of the development of
      radioecology.

PMID- 20050065
TI  - [Effect of the drinking water changed by the hydrogen-oxygen composition on some
      biochemical parameters of experimental animals].
AB  - The biological action of the drinking waters containing different deuterium
      levels (7, 30, 60, 90, 250, and 1000 mg/l) on the activity of N-acetyl-b-D
      glucosaminidase, catalase, the content of triglycerides in the serum and liver
      was studied in a chronic (12-month) experiment on outbred albino mature male
      rats. The animals taking the water containing 145 mg/l of deuterium were chosen
      as a control group. The biochemical studies showed the negative effect of the
      waters on some links of the organism's defense of the organism. The most
      pronounced changes were noted in the group of animals taking the water containing
      1000 mg/l of deuterium.

PMID- 20050066
TI  - [The structure of environmental risk factors to the population's health in the
      Kolsky North].
AB  - The paper considers the problem in the comparative assessment of a carcinogenic
      risk and harm from ionizing irradiation and some chemical ambient air pollutants
      (formaldehyde, suspended matter) to the population's health in the Kolsky
      peninsula. The findings suggest that a chemical risk factor has a much greater
      impact on human health than a radiation risk factor, which should be taken into
      account while developing a nature-conservation policy in the region.

PMID- 20050067
TI  - [Problems of the hygienic study and sanitary assessment of constant magnetic
      fields].
AB  - The paper considers the unsolved problems of the safe use of constant magnetic
      fields. Whether the geomagnetic field attenuation factor is substantiated for
      different population groups is discussed.

PMID- 20050068
TI  - [Methodological problems in the study of the electronic state of the environment
      man system].
AB  - The paper considers the problems associated with the need for hygienic regulation
      of the electronic state of the environment, which affects metabolic changes from
      impaired electronic balance in the primary nonspecific electronic regulation
      system.

PMID- 20050069
TI  - [A methodological approach to studying the values of 50-Hz electromagnetic fields
      that influence the workers of power enterprises].
AB  - The necessity of studying the impact of electromagnetic fields (EMF) on the
      health status of the operation staff from power enterprises has stemmed from the
      improper prior significance being attached to this matter. The subjects of the
      investigations were operators' premises, work environment system, and operation
      staff. The intensity of the electrical and magnetic constituents of a 50-Hz EMF
      in the operation staff's workplaces, in the areas adjacent to 500- and 110
      kVsubstation grounding systems, and in the flats of the approximate apartment
      houses where the workers lived was measured. Then their permissible cumulative
      daily exposure was calculated. Working arrangement was also assessed. The
      examinees' behavior was predicted in stress situations. This permitted a
      scientific rationale to be provided for protective measures against exposure to
      electromagnetic irradiations in productive and nonproductive conditions.

PMID- 20050070
TI  - [Contribution of Iu.M. Lopukhin to the development of medical science and
      education in this country].

PMID- 20050071
TI  - [Physico-chemical investigation of blood components using special fluorescent
      probes].
AB  - The objective of this paper was to overview results of the works aimed at the
      development and practical use of fluorescent dies (molecular flourescent probes)
      for the study of blood components carried out at the Institute of Physico
      Chemical Medicine under the guidance of prof. Yu.M. Lopukhin. The new probes were
      used to directly detect and measure lipoproteins in unfractionated plasma and
      serum for the identification of risk factors of cardiovascular diseases. The
      study revealed changes in physico-chemical characteristics of albumin molecules
      in many pathological processes closely related to clinical features and severity
      of the disease. These data were used to develop a simple albumin test for
      clinical application. Probes for measuring electric field potential in leukocytes
      make it possible to diagnose changes of this parameter in patients with immune
      disorders. It is concluded that they carry diagnostically valuable information
      and may be helpful for recording pathological changes at the cellular and
      molecular levels that can not be observed by traditional laboratory methods.

PMID- 20050072
TI  - [Early non-invasive diagnosis of cardiovascular diseases].
AB  - The study was focused on the assessment of diagnostic significance of cholesterol
      content in the corneal layer of epidermis detected by the method based on
      experimental findings that suggest positive correlation between cholesterol
      levels in aortic endothelium and palm corneal epidermis. Surface cholesterol
      level was measured with the use of digitonin conjugate. A specially developed
      photometer proved a valuable tool for quantitative assay of surface cholesterol.
      Surface cholesterol was detected in epidermis of 649 patients with
      angiographically confirmed stenotic atherosclerosis. Its levels were
      significantly different in patients with different localization of
      atherosclerosis and in age-matched controls. The proposed test was found to be of
      great prognostic value even if its results were highly variable due to the
      necessity of separating free and conjugate-bound cholesterol. The enzyme assay of
      surface cholesterol in epidermis obviates this procedure which significantly
      improves reproducibility of results.

PMID- 20050073
TI  - [Clinical and prognostic significance of free radical processes in patients with
      coronary heart disease].
AB  - The aim of the work was to evaluate the diagnostic and prognostic value of the
      characteristics of processes involving free radicals and of high-performance ECG
      (hpECG) in patients with coronary heart disease (CHD). A new method for early
      assessment of the severity of myocardial ischemia and its electric remodelling
      was developed. Malonic dialdehyde levels (MDA) following Cu-induced oxidation
      during 24 hr were shown to correlate with clinical features of CHD (functional
      class of angina, hpECG patterns). hpECG characteristics changed parallel to MDA
      levels, their frequency was related to the severity of CHD. Long-term prognosis
      of unstable angina (12 month follow-up) was aggravated in patients with MDA level
      of 100 nmol/ml. MDA concentration and its dynamics correlated with CHD severity
      and outcome of acute coronary syndrome (ACS): non-Q wave myocardial infarction
      and angina. All patients with ACS underwent its exacerbation within 5-7 days and
      had depleted plasma antioxidative system. MDA and hpECG dynamics can be used to
      evaluate ACS severity and prognosis as a new diagnostic approach to identifying
      CHD patients with the expected unfavourable outcome of the disease.

PMID- 20050074
TI  - [Phylogenetic, pathogenetic fundamentals and a role of clinical biochemistry in
      classification of arterial hypertension].
AB  - Classifications of the clinical forms of arterial hypertension (AH) are aimed at
      differentiating it on etiological grounds; we propose a classification that is
      based on the common pathogenesis of hydrodynamic pressure elevation in the
      intravascular pool of the intercellular medium, i.e. arterial blood pressure
      (BP). We believe that there are only three options for hydrodynamic pressure
      elevation in a mechanical model of the cardiovascular system: 1) a decrease in
      the volume of the arterial bed at a constant volume of intravascular fluid; 2) an
      increase in the volume of intravascular fluid at a constant volume of the
      vascular bed; and 3) increased blood flow resistance at constant volumes of the
      vascular bed and intravascular fluid. These options cover all clinical forms of
      AH in which AP increase is governed by common mechanisms. The first option can be
      related to AH occurring in pheochromoblastoma, glucocorticoid hyperproduction and
      psychoemotional stress. The second is associated with AH developing in excessive
      NaCl consumption with food, increased aldosterone production in Conn's syndrome
      (primary aldosteronism) and reduced production of atrial natriuretic peptide by
      phylogenetically modified myocytes of the right atrium. The third option can be
      linked to all forms of increased peripheral blood flow resistance in the arterial
      bed occurring in coarctation of the aorta, renovascular hypertension, impaired
      flow (endothelium)-dependent vasodilation and moderate spasm of muscular
      arterioles, arterial wall lesion in atherosclerosis, atheromatosis and
      atherothrombosis, Takayasu syndrome, and obliterating endarteritis. Elevation of
      BP in erythemia, under the effect of leukocyte colony-stimulating factor and
      after injection of a recombinant erythropoietin can also be regarded within the
      frames of the third option. From the viewpoint of general biology, all forms of
      AH developing against the background of impaired biological function of
      transcytosis (macropinocytosis) and crossing by food substrates and humoral
      mediators of bilayer structures between the common and local pools of the
      intercellular medium, i.e. blood-brain barrier can be referred to as a
      hematoencephalitic form. Arterial hypertension developing in impaired
      transcytosis across the blood-brain barrier (endothelium+ astrocytes bilayer), an
      encephalopathic form; endothelium+ podocytes bilayer, a renal form;
      endothelium+trophoblasts, placental AH; endothelium +/- pheumocytes, pulmonary
      AH; and endothelium+intimal macrophages, atherosclerosis-related AH. Normal AP
      points to: 1) the physiological level of transcytosis between all pools of the
      intercellular medium; 2) the absence of peripheral blood flow resistance in the
      arterial bed; 3) normal function of muscle arterioles; and 4) the physiological
      levels of metabolic processes in all paracrine cell communities in vivo.

PMID- 20050075
TI  - [Bone resorption and formation markers in women with climacteric syndrome in
      early postmenopause].
AB  - The level of bone metabolites and the indices of calcium and phosphorus
      metabolism were measured in 20 women with climacteric syndrome in postmenopause
      and in 20 women in premenopause, who had normal bone density and did not differ
      in the modified risk factors of osteoporosis. In the climacteric women, the
      normal bone density was accompanied by the elevated levels of CrossLaps and
      osteocalcin. There was no difference in the concentrations of parathormone,
      calcium, and phosphorus. After 9-month non-hormonal correction of climacteric
      syndrome with Estrovel (Ecomir, Russia), the levels of CrossLaps reduced by 45%
      and that of osteocalcin became normal.

PMID- 20050076
TI  - [Assessing the conformity of medical devices for in vitro diagnosis:
      international and domestic experience].
AB  - The conformity of medical articles was assessed for in vitro diagnosis is the
      most importance procedure for their entering the market. This paper describes the
      basic elements of assessment of the conformity of these articles, analyzes
      worldwide experience, shows differences in the Russian regulatory system in the
      circulation of medical articles for in vitro diagnosis, and gives recommendations
      for its improvement.

PMID- 20050077
TI  - Reminders about wound closure.

PMID- 20050078
TI  - By the way, doctor.  Fifteen years ago, I had surgery for a torn meniscus and was
      told I had arthritis.  I'm now 79, and my knee hurts most days, though I still
      exercise daily on a stationary bike.  I hate to take pills.  Should I consider a
      knee replacement?

PMID- 20050079
TI  - The psychological cost of foreclosure.

PMID- 20050080
TI  - Municipal solid waste management at Taman Beringin Transfer Station in Malaysia.

PMID- 20050081
TI  - Emergent right lobe adult-to-adult living-donor liver  transplantation for high
      model for end-stage liver disease  score severe hepatitis.
AB  - The aim of this study was to explore the feasibility of emergency right lobe
      adult-to-adult living-donor liver transplantation (LDLT) for high model for end
      stage liver disease (MELD) score severe hepatitis. Consecutive 10 high MELD score
      severe hepatitis patients underwent emergency right lobe adult-to-adult LDLT in
      our hospital from April to December 2007. The MELD score was 34.50 +/- 2.088. The
      outcomes of these recipients were retrospectively analyzed. Among them, eight
      cases of ABO blood group were identical and two cases compatible, one case was Rh
      negative. Two recipients died and the rest of the recipients and all donors are
      safe; perioperative and 2-year survival rate was 80%. The mean graft-recipient
      weight ratio (GRWR) was 1.27% +/- 0.25%, and graft volume to recipient standard
      liver volume ratio (GV/ESLVR) was 56.7% +/- 6.75%. Of the 10 patients, three
      received right lobe grafts with middle hepatic vein (MHV), four without MHV,
      three without MHV but followed by V and VIII hepatic vein outflow reconstruction.
      An encouraging outcome was achieved in this group: elevated serum creatinine,
      serum endotoxin, decreased serum prothrombin activity, and Tbil returned to
      normal on postoperative days 3, 7, 14, and 28, respectively. One-year survival
      rate was 80%. Outcomes of emergency right lobe adult-to-adult LDLT for high MELD
      score severe hepatitis were fairly encouraging and acceptable. Emergency right
      lobe adult-to-adult LDLT is an effective and life-saving modality for high MELD
      score acute liver failure patients following severe hepatitis.

PMID- 20050082
TI  - The role of spirituality in mental wellbeing.

PMID- 20050083
TI  - Report on the views of patients on mental health wards has just come out.

PMID- 20050084
TI  - Have faith.

PMID- 20050085
TI  - Beyond bars.

PMID- 20050086
TI  - On the road to recovery.

PMID- 20050087
TI  - Proposed changes in assisted suicide.

PMID- 20050088
TI  - Being unemployed today.

PMID- 20050089
TI  - Tougher financial targets new regulatory standards.

PMID- 20050090
TI  - Up close and personal.

PMID- 20050091
TI  - Meeting the mental health needs of older people from black and minority ethnic
      communities.

PMID- 20050092
TI  - 'Showcase Live'!

PMID- 20050093
TI  - Riding out the recession.

PMID- 20050094
TI  - The views of nearest relatives really must be heeded.

PMID- 20050096
TI  - Living with mental illness. Interview by Alita Howe.

PMID- 20050095
TI  - Direct payments.

PMID- 20050098
TI  - Free tutorial.

PMID- 20050097
TI  - [China make a great effort on public health care].

PMID- 20050099
TI  - Critical aspects in hypertension diagnosis and treatment.

PMID- 20050100
TI  - Quality of life and efficacy of nebivolol in an open-label study in hypertensive
      patients. the QoLaN study.
AB  - BACKGROUND: Nebivolol is a highly selective beta-adrenoreceptor antagonist with
      vasodilating properties. This study investigated its effect on quality of life
      (QoL) and blood pressure (BP) in real life conditions. In total, 1468 patients
      were enrolled, 12% diabetics. Nebivolol was prescribed as monotherapy, add-on or
      switch medication. METHODS: In this open-label, prospective study, the JNC-VII BP
      target values were used: < 140/90 and < 130/80 mmHg for diabetics. The responder
      rate and the QoL was determined at baseline and after 4 and 8 weeks. RESULTS:
      After 4 weeks, 27% of subjects reached target BP, 45% after 8 weeks. The
      responder rates were 92, 90 and 83% for the monotherapy, add-on and switch
      groups. Compared with baseline, all showed statistical significance at 8 weeks.
      Similarly to results for the QoL after 8 weeks, the mean improvement in QoL for
      all three groups was 9-10 points (total range: 0-88). CONCLUSIONS: The study
      demonstrates that nebivolol in mild to moderate hypertension is associated with
      overall improvements in QoL, with a marked BP-lowering effect, in monotherapy,
      add-on or switch, irrespective of the glucose tolerance status. It may be
      hypothesized that its dual mode of action explains its BP-lowering effect as well
      as the tolerability.

PMID- 20050101
TI  - Validation of four automatic devices for self-measurement of blood pressure
      according to the International Protocol: the Pic Indolor Personal Check, Comfort
      Check, My Check and Travel Check.
AB  - OBJECTIVE: Four oscillometric devices for self-measurement of blood pressure
      (SBPM) were evaluated according to the International Protocol of the European
      Society of Hypertension (ESH) in four separate studies. The Pic Indolor Personal
      Check, Comfort Check and My Check measure blood pressure (BP) at the brachial
      level; the Travel Check measures radial BP at the wrist level. METHODS: The
      International Protocol includes a total number of 33 subjects. In each study and
      for each subject, four BP measurements were performed simultaneously by two
      observers using mercury sphygmomanometers alternately with three measurements by
      the tested device. The difference between the observers and the device BP values
      (99 pairs) were classified into three categories (< or =5, < or =10, < or =15
      mmHg). RESULTS: All four tested devices passed the validation process. The mean
      differences between the device and mercury readings were 0.1 +/- 2.9 and -0.1 +/-
      3.8 mmHg for systolic and diastolic BP respectively for the Personal Check; -1.0
      +/- 3.7 and 0.2 +/- 3.2 mmHg for the Comfort Check; -0.6 +/- 4.5 and -1.5 +/- 4.3
      mmHg for the My Check; -0.1 +/- 2.0 and 0.6 +/- 1.7 mmHg for the Travel Check.
      CONCLUSION: Readings of the Pic Indolor Personal Check, Comfort Check, My Check
      and Travel Check devices differing by less than 5, 10 and 15 mmHg fulfill the
      International Protocol requirements and therefore can be used by patients for
      SBPM.

PMID- 20050102
TI  - Empathy among medical    school applicants.

PMID- 20050103
TI  - Correlation of attendance    pattern with academic    performance of medical   
      undergraduates in pediatrics.

PMID- 20050104
TI  - Is Wikipedia unsuitable as a    clinical information resource    for medical
      students?

PMID- 20050105
TI  - The need for education in     ultrasonography.

PMID- 20050106
TI  - Designing international    health electives using the    CanMEDS core   
      competencies.

PMID- 20050107
TI  - Establishing a conference for    a small program.

PMID- 20050108
TI  - Student perceptions of the    influence of visual imagery in    medical school
      application    prospectuses in the UK.

PMID- 20050109
TI  - [Malformations and fetal death in the Spanish antiepileptic drug and pregnancy
      registry: results at 6 years].

PMID- 20050110
TI  - [Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease)].

PMID- 20050111
TI  - [Neurological attention to the immigrant population in Almeria].

PMID- 20050112
TI  - [Treatment of tetanus with intrathecal baclofen].

PMID- 20050113
TI  - [Globalization, stroke and Chagas disease on the hundredth anniversary of its
      discovery].

PMID- 20050114
TI  - [Neurological manifestations in accidental poisoning by homeopathic kerosene].

PMID- 20050115
TI  - [Oligodendroglioma simulating acute herpetic encephalitis].

PMID- 20050116
TI  - [Amyotrophic lateral sclerosis syndrome-plus and consumption of cassava
      (Manihot). Is this a new presentation of the neurotoxic motor-neuron syndrome?].

PMID- 20050117
TI  - [Massive fatal subarachnoid haemorrhage after carotid angioplasty and stenting].

PMID- 20050118
TI  - [Acute hyperammonemic encephalopathy in ornithine transcarbamylase deficiency].

PMID- 20050119
TI  - [Peripheral facial paralysis as a first symptom of a pulmonary metastasis].

PMID- 20050120
TI  - [Potassium: something else to think about in progressive paralysis patient].

PMID- 20050121
TI  - [Acute myopia secondary to treatment with topiramate].

PMID- 20050122
TI  - [Lacunar infarction with aphasic semiology secondary to a diaschisis phenomenon].

PMID- 20050124
TI  - Patient information page from the Hormone Foundation. Klinefelter syndrome.

PMID- 20050123
TI  - A Festschrift honoring Shukri F. Khuri, MD: celebrating 15 years of NSQIP
      (National Surgical Quality Improvement Program). The 33rd Annual Meeting of the
      Association of VA Surgeons. April 19. 2009. Boston, Massachusetts, USA.

PMID- 20050125
TI  - Blast crisis.

PMID- 20050126
TI  - [Severe chondrolysis after shoulder arthroscopy: a case series].

PMID- 20050127
TI  - Reduction of cyclosporine following the introduction  of everolimus in
      maintenance heart transplant recipients:  a pilot study.
AB  - Data are scarce concerning the calcineurin inhibitor dose reduction required
      following introduction of everolimus in maintenance heart transplant recipients
      to maintain stable renal function. In a 48-week, multicenter, single-arm pilot
      study in heart transplant patients >12 months post-transplant, everolimus was
      started at 1.5 mg/day (subsequently adjusted to target C(0) 5-10 ng/ml).
      Mycophenolate mofetil or azathioprine was discontinued on the same day and
      cyclosporine (CsA) dose was reduced by 25%, with a further 25% reduction each
      time calculated glomerular filtration rate (cGFR) decreased to <75% of baseline.
      Of 36 patients enrolled, 25 were receiving everolimus at week 48. From baseline
      to week 48, there was a mean decrease of 44.5%, 50.9% and 44.6% in CsA dose, C(0)
      and C(2), respectively. Mean cGFR was 68.9 +/- 14.5 ml/min at baseline and 61.6
      +/- 11.5 ml/min at week 48 (P = 0.018). The prespecified criterion for stable
      renal function was met, i.e. a mean decrease <or=25% of cGFR from baseline. Two
      patients experienced biopsy-proven acute rejection Grade 3A (5.6%). Between
      baseline and week 48, there were significant increases in total cholesterol, LDL
      cholesterol and triglycerides, and small but significant elevations in liver
      enzymes. This 1-year pilot study suggests that CsA dose reduction of ca. 40%
      after initiation of everolimus was associated with a decrease in cGFR, however,
      based on the prespecified criteria stable renal function was attained.

PMID- 20050128
TI  - Beware of neuronal Sunday drivers: Sunday Driver interacts with two distinct
      classes of axonal organelles.

PMID- 20050129
TI  - Helmut Drexler, MD,   1951-2009.

PMID- 20050130
TI  - Symposium: Tribute to Dr. Marshal Urist: musculoskeletal growth factors.

PMID- 20050131
TI  - Complications of hydroxyethyl starch in paediatric patients.

PMID- 20050132
TI  - On call.  My wife and I both enjoy the "Harvard Men's Health Watch" newsletter. 
      We've read that erectile dysfunction can be a warning for future heart disease in
      men.  I'm okay in the department, but my wife is experiencing a drop in her sex
      drive.  She'll be seeing her gynecologist for help, but we wonder if she should
      see a cardiologist, too.

PMID- 20050133
TI  - Prisons.  Denial of HAART does not constitute deliberate indifference.

PMID- 20050134
TI  - Employment.  Administrators did not know employee was HIV positive.

PMID- 20050136
TI  - Proceedings of the Endoscopy Forum, Japan 2007-2008.

PMID- 20050135
TI  - Vaccines.  Group launches first H1N1 trial for HIV-infected pregnant women.

PMID- 20050137
TI  - Proceedings of the International Conference "COPD: Reactive Past, Preventive
      Future", Vancouver, Canada, February 6-7, 2009.

PMID- 20050140
TI  - Comments on cardiac markers article.

PMID- 20050141
TI  - Trigger points comment.

PMID- 20050144
TI  - Proceeding of a symposium honoring Ernest Everett Just, November 21, 2008,
      Washington DC, USA.

PMID- 20050145
TI  - Commentary.

PMID- 20050146
TI  - Commentary.

PMID- 20050147
TI  - [The 49th Annual Meeting of the Japanese Society of Neuropathology. Tokyo, Japan.
      May 20-22, 2008. Abstracts].

PMID- 20050148
TI  - Commentary.

PMID- 20050149
TI  - Commentary.

PMID- 20050150
TI  - Re: Topical 10% zinc sulfate solution for treatment of melasma.

PMID- 20050151
TI  - Destructive basal cell carcinoma in a patient with basal cell nevus syndrome and
      an interstitial deletion of chromosome 9q22.

PMID- 20050153
TI  - [The 55th Annual Meeting of the Japanese Society of Clinical Pathology. Nagoya,
      Japan. November 27-30, 2008. Abstracts].

PMID- 20050152
TI  - A useful tool for design of the W-plasty in the excision of irregular lesions.

PMID- 20050154
TI  - [The 101st Annual Meeting of the Japanese Society of Animal Reproduction.
      Fukuoka, Japan. September 18-20, 2008. Abstracts].

PMID- 20050155
TI  - Proceedings of the 2009 Bovine Respiratory Disease (BRD) Symposium,  5-6 August
      2009, Colorado Springs, Colorado, USA. Introduction.

PMID- 20050156
TI  - Retraction. Allelic variation in the serotonin transporter promoter modulates
      cortical excitability.

PMID- 20050157
TI  - Retraction. Changes in integument histology and protein expression related to the
      molting cycle of the black tiger shrimp, Penaeus monodon.

PMID- 20050158
TI  - [Pressure injuries. Prevention of pressure injuries].

PMID- 20050159
TI  - [Structural and functional specificity of the Dichelobacter nodosus pili.
      Synthesis of the protein pilin of D. nodosus in various bacterial recombinant
      strains].
AB  - The ovine foot rot is a severe infectious disease of sheep. Dichelobacter nodosus
      is an essential pathogen of this disease. An obligatory anaerobic gram-negative
      rod-shaped microorganism has slow rate of accumulating bacterial density and
      fastidious growth requirements. This causes obstacles to vaccine production and
      makes it difficult to diagnose the disease. The diagnosis in this case is more
      expensive. Fimbriae (or pili) are one of the major factors of virulence of D.
      nodosus. Their antigenic and immunogenic properties make them good vaccine
      components for elevated immunogenicity. Since the nucleotide sequence of the fimA
      gene encoding fimbrial subunit was determined, attempts to produce recombinant
      pili were undertaken. The production of the genetic-engineering fimbriae would
      allow the price of the vaccines to be reduced and their manufacture to be
      simplified. The vaccine immunogenicity is increased in this case. At first, E.
      coli was selected as an expression system, but morphogenetic expression of the
      pili was not achieved on its surface because of some differences in the
      biogenesis and structure of fimbriae from D. nodosus. Successful morphogenesis of
      the pili was achieved in Pseudomonas aeruoginosa, which had closest similarity in
      the structure of pili. The level of the immunity obtained after immunization of
      the sheep with recombinant pili was similar to the level of the immunity after
      native pili or whole cells of D. nodosus had been used. This review contains
      information regarding the recombinant strains of Pseudomonas aeruoginosa obtained
      using fimbriae of D. nodosus and expression of pilin genes in different bacterial
      systems.

PMID- 20050160
TI  - [Molecular mechanisms of the plague pathogenic agent interaction with
      invertebrates].
AB  - Microbe Russian Anti-Plague Research Institute, Saratov, Russia The literature
      data and experimental results of the authors on the molecular basis of plague
      agent interaction with invertebrates are discussed. The details of the plague
      agent life cycle, its genome organization, and molecular genetic mechanisms of
      its survival in flea vector and on the nematode cuticule are discussed. The
      experimental data about the ability to form biofilms at abiotic and biotic
      surfaces in the Yersinia pestis strains of the main and non-main subspecies are
      presented. Mechanisms of horizontal and vertical transmission of plague agent are
      considered. The suggestion about participation of the new member in the complex
      parasitic biocenosis (nematode, vector parasite) is put forward.

PMID- 20050161
TI  - [The heterogeneity of the ospa gene of Borrelia garinii and Borrelia afzelii in
      western Siberia and Mongolia].
AB  - 48 full-length Borrelia garinii and Borrelia afzelii from West Siberia and
      Mongolia ospA gene nucleotide sequences was determined. Four groups of Borrelia
      garinii were revealed using the analysis of nucleotide sequences. The most
      variable ospA gene region was demonstrated to be included in region where the
      antigenic determinants of protein were encoded. High homology level was shown for
      nucleotide sequences corresponding to isolates of Borrelia afzelii.

PMID- 20050162
TI  - [Genomic polymorphism of the main subspecies of the plague agent strains].
AB  - Genomic fingerprinting analysis of plague agent strains of the main subspecies
      isolated in natural foci of various types in the Russian Federation and
      neighboring countries suggests their genetic polymorphism, while they are similar
      in phenotypic properties. The strains of the main subspecies, Y. pesis subsp.
      Pestis, fall into four genetic variants, each of them being associated with
      specific carrier species. The conserved genomic fingerprinting profile of each
      genovariant of Y. pesis subsp. Pestis strains ensures the suggested methodic
      approach to be promising for the intraspecies differentiation of plague agent
      strains (including atypical strains). Correlation of genovariants with carrier
      species permits their application for research into enzootic territories, where
      carrier change-over takes place.

PMID- 20050163
TI  - [Many-level polysensory stimulation of brain functions by physical therapeutic
      agents].
AB  - A combination of physiotherapeutic methods for neurorehabilitative treatment has
      been developed and applied to the treatment of 576 patients with neurosurgical
      problems including the loss of brain functions as a sequel to nervous system
      lesions of traumatic, vascular, and other origin. Methodologically, this complex
      is adapted to the level and extent of the lesion and the character of
      regeneration of the nervous tissues. It implies many-level stimulation of
      neuroregeneration by syndromically and pathogenetically substantiated application
      of physical factors in the early post-injury and postoperative periods. The
      proposed approach allows the brain function to be completely restored by virtue
      of persistent compensatory changes in the nervous system. A combination of many
      level magnetic, electrical, and laser stimulation is recommended to manage
      lesions in the speech, motor, and visual analyzers. Combined laser and
      differential electrostimulation may be prescribed to patients with nerve lesions,
      extremely high frequency therapy to those with epileptic syndrome, combined
      microwave therapy to cases with impairment of consciousness, and a variant of
      systemic UV irradiation with underwater shower-massaging for the treatment of
      vegetative and asthenic disturbances. Selected physiological aspects of the
      action of the above physical factors are specified. This physiotherapeutic system
      is protected by 20 RF patents of invention.

PMID- 20050164
TI  - [The strategy of rehabilitative treatment following surgical intervention in
      patients with pseudoarthrosis of the extremities].
AB  - The objective of the present study was to analyse results of the treatment of 267
      patients with pseudoarthrosis of the extremities and to use them for the
      development of criteria for the choice of methods for rehabilitative therapy. It
      was shown that stability of fixation of bone fragments by metal devices in
      patients with false joints (unlike fractures) varies depending on bone tissue
      condition. With this in mind, the patients receiving rehabilitative treatment
      were allocated to three groups differing in the degree of immobilization in the
      postoperative period. One group included the patients who did not need
      immobilization of the affected extremity. The other comprised those requiring
      immobilization only in case of axial load. Patients of the third group needed
      immobilization throughout the entire period until the completion of fragment
      consolidation. The results thus obtained were used to develop tactical schemes of
      combined treatment of patients using up-to-date orthotic techniques. It is
      proposed to divide the postsurgery treatment schedule into the following periods:
      early postoperative, early rehabilitative, the onset of active functional
      loading, and the period of functional and vocational rehabilitation. Such a
      differentiation is believed to enhance efficiency of the above rehabilitative
      strategy and facilitate the adequate choice of combined remedial treatments.
      Excellent and good outcome of rehabilitation with the use of this technology have
      been achieved in 98.9% of the patents.

PMID- 20050165
TI  - [The role of natural medicinal factors in federal and regional recreational zones
      in the rehabilitation of patients following surgical treatment of pathological
      periapical tissues and oral cavity phlegmonas].
AB  - The necessity of considering the problem with which this paper is concerned
      arises from the current scientific discussion of the actions of physicians
      working in municipal healthcare facilities and sanatoria directed toward
      rehabilitation of patients after surgical treatment of periapical tissues and
      oral cavity phlegmonas. The study elucidated the mechanism of action of mineral
      waters (alkaline, sodium hydrocarbonate or boron-containing water with elevated
      fluorine and chlorine content) extracted from natural deposits of the Belgorod
      Region and Krasnodar Krai (Territory). It was shown that drinking these waters
      contributed to the correction of the disturbed balance in the ratio of sodium and
      potassium ions excreted with urine and to the positive dynamics of serum
      phosphorus level in the patients included in this study.

PMID- 20050166
TI  - [The influence of peloids from volcanic deposits in Azerbaijan on the dynamics of
      sugar content in blood and urine and the wound healing in patients at the early
      stages of diabetic gangrene of the lower extremities].
AB  - The treatment of diabetic patients with pyonecrotic lesions in the lower
      extremities requires prolonged reflexo-segmental balneophysiotherapy to normalize
      functions of the nerve centres. Curative volcanic mud solutions (15-24 g/l)
      enriched with organic and nonorganic biologically active compounds from volcanic
      deposits in Azerbaijan were used for the first time to treat such patients.
      Peloids were applied to the lumbar region (location of sympathetic nerve nodes)
      and the lower legs above and beneath the affected sites. The patients were
      subjected to 12-15 seances of peloidotherapy (at 40-41 degrees Celsius) each
      lasting 20-30 minutes. The treatment was preceded by wound sanation using the
      standard procedure and a course of antibiotic therapy based on individual
      antibiotocograms. A total of 86 daibetic patients with leg gangrene underwent
      rheovasographic thermovision examination that revealed enhanced blood supply to
      the affected extremities under the action of the applied peloids. Peloidotherapy
      resulted in the normalization of blood and urine glucose levels in 53 (63%) of
      the patients. Simultaneously, the doses of medicamentous therapy could be
      lowered. Wound and ulcer healing was completed in the majority of the patients
      (86%) by the end of balneophysiotherapy when fresh granulation tissue began to
      develop and signs of oedema to disappear. These patients no longer needed
      amputation.

PMID- 20050167
TI  - [Evgenii Danilovich Gol'dberg and development of pharmacology in Siberia].

PMID- 20050168
TI  - Charles Saul Lieber, a tribute (13 February 1931 to 1 March 2009).

PMID- 20050169
TI  - Tylenol and vaccines--something to avoid?

PMID- 20050170
TI  - ...And expert commentary.

PMID- 20050171
TI  - Do fever reducers prevent repeat febrile seizures?

PMID- 20050172
TI  - ...And what's best for fracture pain in children?

PMID- 20050173
TI  - Do hand sanitizers pose a risk to children?

PMID- 20050174
TI  - A caution about giving Tamiflu to children.

PMID- 20050175
TI  - Product recalls.  Recalls: Children's Animal Masks and Pendants...Clarks
      children's shoes due to choking hazard...and Baby Jogger Strollers.

PMID- 20050176
TI  - Ti: myths about monoamine oxidase inhibitors  perpetuated.

PMID- 20050177
TI  - Cervical cancer: problem solved? Vaccinating girls against human papillomavirus.

PMID- 20050178
TI  - [Pregnancy and venous thromboembolism. North-American and European guidelines.
      American College of Chest Physicians].
AB  - Guidelines concerning the prevention and treatment of pregnancy-associated venous
      thromboembolism (VTE) have been elaborated by the American College of Chest
      Physicians and published in Chest in 2008. In this review, they have been
      compared with European guidelines and discussed taking into account the papers
      published since 2008.Most recommendations are of low grade of evidence because
      randomized studies are lacking during pregnancy and many reflect guidelines
      proposed by experts. The decisions on the most appropriate prophylaxis, dose to
      be administered and moment of pregnancy for starting prophylaxis are often
      decided case by case after careful assessment of the risk of pregnancy-associated
      VTE, on one hand, and the risk for the mother, on the other.Risk factors (age
      >or= 35, obesity, history of VTE with or without sequellae, in vitro
      fertilization)or thrombophilia have to be taken into account. Scores have been
      proposed to improve standardisation and evaluation of the risk of VTE and they
      should be validated.

PMID- 20050179
TI  - [Limb lymphedema: Diagnosis, explorations, complications. French Lymphology
      Society].
AB  - Lymphedema results from impaired lymphatic transport with increased limb volume.
      Primary and secondary forms can be distinguished. Secondary lymphedema of the
      upper limb is the most frequent in France. A 2-cm difference on any segment of
      the limb confirms the diagnosis of lymphedema. Calculated lymphedema volume using
      the formula for a truncated cone is required to assess the efficacy of treatment
      and to monitor follow-up. Primary lymphedema is sporadic but rarely familial.
      Lymphoscintigraphy is useful in the primary form to evaluate precisely lymphatic
      function of the two limbs. Erysipelas is the main complication,but psychological
      or functional discomfort may occur throughout the course of lymphedema. Lipedema
      is the main differential diagnosis, defined as an abnormal accumulation of fat
      from hip to ankle and occurs almost exclusively in obese women.

PMID- 20050180
TI  - Modulation of sterol homeostasis by the Cdc42p effectors  Cla4p and Ste20p in the
      yeast Saccharomyces cerevisiae.
AB  - The conserved Rho-type GTPase Cdc42p is a key regulator of signal transduction
      and polarity in eukaryotic cells. In the yeast Saccharomyces cerevisiae, Cdc42p
      promotes polarized growth through the p21-activated kinases Ste20p and Cla4p.
      Previously, we demonstrated that Ste20p forms a complex with Erg4p, Cbr1p and
      Ncp1p, which all catalyze important steps in sterol biosynthesis. CLA4 interacts
      genetically with ERG4 and NCP1. Furthermore, Erg4p, Ncp1p and Cbr1p play
      important roles in cell polarization during vegetative growth, mating and
      filamentation. As Ste20p and Cla4p are involved in these processes it seems
      likely that sterol biosynthetic enzymes and p21-activated kinases act in related
      pathways. Here, we demonstrate that the deletion of either STE20 or CLA4 results
      in increased levels of sterols. In addition, higher concentrations of steryl
      esters, the storage form of sterols, were observed in cla4Delta cells. CLA4
      expression from a multicopy plasmid reduces enzyme activity of Are2p, the major
      steryl ester synthase, under aerobic conditions. Altogether, our data suggest
      that Ste20p and Cla4p may function as negative modulators of sterol biosynthesis.
      Moreover, Cla4p has a negative effect on steryl ester formation. As sterol
      homeostasis is crucial for cell polarization, Ste20p and Cla4p may regulate cell
      polarity in part through the modulation of sterol homeostasis.

PMID- 20050182
TI  - Electrostatic contacts in the activator protein-1 coiled coil enhance stability
      predominantly by decreasing the unfolding rate.
AB  - The hypothesis is tested that Jun-Fos activator protein-1 coiled coil
      interactions are dominated during late folding events by the formation of
      intricate intermolecular electrostatic contacts. A previously derived cJun-FosW
      was used as a template as it is a highly stable relative of the wild-type cJun
      cFos coiled coil protein (thermal melting temperature = 63 degrees C versus 16
      degrees C), allowing kinetic folding data to be readily extracted. An
      electrostatic mutant, cJun(R)-FosW(E), was created to generate six Arg-Glu
      interactions at e-g'+1 positions between cJun(R) and FosW(E), and investigations
      into how their contribution to stability is manifested in the folding pathway
      were undertaken. The evidence now strongly indicates that the formation of
      interhelical electrostatic contacts exert their effect predominantly on the
      coiled coil unfolding/dissociation rate. This has major implications for future
      antagonist design whereby kinetic rules could be applied to increase the
      residency time of the antagonist-peptide complex, and therefore significantly
      increase the efficacy of the antagonist.

PMID- 20050183
TI  - Helicobacter species in the human colon.
AB  - OBJECTIVE: To determine the prevalence, frequency and colonization patterns of
      Helicobacter species throughout the colon. METHOD: Patients having initial
      colonoscopy for nonspecific gastrointestinal disturbance had colonic biopsies
      taken from up to four sites during colonoscopy and examined for evidence of the
      Helicobacteraceae family using a group-specific PCR. Serum was also collected and
      examined for IgG reactivity to Helicobacter pylori. RESULTS: 100 patients had
      colonoscopy of whom 35 were found to have DNA evidence of Helicobacter species
      throughout the colon, with 22 having H. pylori. Fifteen patients had a
      demonstrable serum IgG response to H. pylori that was not always associated with
      molecular evidence of H. pylori DNA in colon biopsies and vice versa. No specific
      association with colon disease was found in patients with H. pylori infection.
      CONCLUSION: We found evidence of Helicobacter infection in a significant number
      of patients presenting for colonoscopy but no specific association between the
      presence of these bacteria and colon disease. Our finding of disparity between
      molecular and serological techniques to detect Helicobacter species suggests that
      future studies should not rely on serology alone to detect these bacteria in the
      human colon.

PMID- 20050184
TI  - Positive allosteric modulation of alpha7 neuronal nicotinic acetylcholine
      receptors: lack of cytotoxicity in PC12 cells and rat primary cortical neurons.
AB  - BACKGROUND AND PURPOSE: alpha7-Nicotinic acetylcholine receptors (alpha7 nAChRs)
      play an important role in cognitive function. Positive allosteric modulators
      (PAMs) amplify effects of alpha7 nAChR agonist and could provide an approach for
      treatment of cognitive deficits in neuropsychiatric diseases. PAMs can either
      predominantly affect the apparent peak current response (type I) or increase both
      the apparent peak current response and duration of channel opening, due to
      prolonged desensitization (type II). The delay of receptor desensitization by
      type II PAMs raises the possibility of Ca2+-induced toxicity through prolonged
      activation of alpha7 nAChRs. The present study addresses whether type I and II
      PAMs exhibit different cytotoxicity profiles. EXPERIMENTAL APPROACH: The present
      studies evaluated cytotoxic effects of type I PAM [N-(4-chlorophenyl)]-alpha-[(4
      chlorophenyl)-aminomethylene]-3-methyl-5-isoxazoleacet-amide (CCMI) and type II
      PAM 1-[5-chloro-2,4-dimethoxy-phenyl]-3-[5-methyl-isoxazol-3-yl]-urea (PNU
      120596), or 4-[5-(4chloro-phenyl)-2-methyl-3-propionyl-pyrrol-1-yl]
      benzenesulphonamide (A-867744). The studies used cultures of PC12 cells and
      primary cultures of rat cortical neuronal cells. KEY RESULTS: Our results showed
      that neither type I nor type II PAMs had any detrimental effect on cell integrity
      or cell viability. In particular, type II PAMs did not affect neuron number and
      neurite outgrowth under conditions when alpha7 nAChR activity was measured by
      Ca2+ influx and extracellular signal-regulated kinases 1 and 2 phosphorylation,
      following exposure to alpha7 nAChR agonists. CONCLUSIONS AND IMPLICATIONS: This
      study demonstrated that both type I and type II alpha7 nAChR selective PAMs,
      although exhibiting differential electrophysiological profiles, did not exert
      cytotoxic effects in cells endogenously expressing alpha7 nAChRs.

PMID- 20050185
TI  - Multiple muscarinic pathways mediate the suppression of voltage-gated Ca2+
      channels in mouse intestinal smooth muscle cells.
AB  - BACKGROUND AND PURPOSE: Stimulation of muscarinic receptors in intestinal smooth
      muscle cells results in suppression of voltage-gated Ca2+ channel currents
      (I(Ca)). However, little is known about which receptor subtype(s) mediate this
      effect. EXPERIMENTAL APPROACH: The effect of carbachol on I(Ca) was studied in
      single intestinal myocytes from M2 or M3 muscarinic receptor knockout (KO) and
      wild-type (WT) mice. KEY RESULTS: In M2KO cells, carbachol (100 microM) induced a
      sustained I(Ca) suppression as seen in WT cells. However, this suppression was
      significantly smaller than that seen in WT cells. Carbachol also suppressed I(Ca)
      in M3KO cells, but with a phasic time course. In M2/M3-double KO cells, carbachol
      had no effect on I(Ca). The extent of the suppression in WT cells was greater
      than the sum of the I(Ca) suppressions in M2KO and M3KO cells, indicating that it
      is not a simple mixture of M2 and M3 receptor responses. The G(i/o) inhibitor,
      Pertussis toxin, abolished the I(Ca) suppression in M3KO cells, but not in M2KO
      cells. In contrast, the G(q/11) inhibitor YM-254890 strongly inhibited only the
      I(Ca) suppression in M2KO cells. Suppression of I(Ca) in WT cells was markedly
      reduced by either Pertussis toxin or YM-254890. CONCLUSION AND IMPLICATIONS: In
      intestinal myocytes, M2 receptors mediate a phasic I(Ca) suppression via G(i/o)
      proteins, while M3 receptors mediate a sustained I(Ca) suppression via G(q/11)
      proteins. In addition, another pathway that requires both M2/G(i/o) and
      M3/G(q/11) systems may be operative in inducing a sustained I(Ca) suppression.

PMID- 20050186
TI  - P2X2, P2X4 and P2Y1 receptors elevate intracellular Ca2+ in mouse embryonic stem
      cell-derived GABAergic neurons.
AB  - BACKGROUND AND PURPOSE: Neurons derived from mouse embryonic stem cells (mESCs)
      are a valuable resource for basic pharmacological research. With the exception of
      cardiomyocytes, there is relatively little understanding of the pharmacology of
      stem cell-derived differentiated cells. In this study we investigate P2 receptor
      agonist effects on GABAergic neurons derived from mESCs. EXPERIMENTAL APPROACH:
      mESCs were differentiated into GABAergic neurons in the presence of N2B27 culture
      medium. At day 24 of differentiation GABAergic neuronal responsiveness to
      purinergic agonists was investigated using calcium imaging and [3H]-GABA release
      studies. KEY RESULTS: Sub-populations of GABAergic neurons responded to some or
      all of the adenine and uracil nucleotides ATP, ADP, UTP and UDP (all 100 microM)
      with elevations of intracellular Ca2+ ([Ca2+]i). The number of neurons responding
      to ATP was reduced by suramin (100 microM), PPADS (10 microM) and MRS2179 (10
      microM), but not by NF023 (10 microM). The response to ATP was modulated by
      extracellular Zn2+ and pH. Neurons also responded to ATP (100 microM) with the
      release of [3H]-GABA, an effect completely inhibited by tetrodotoxin (100 nM).
      Ap4A and 2-methylthioATP both elicited significant [3H]-GABA release. Reverse
      transcriptase PCR showed the presence of P2X1,2,3,4,5,6 and P2X7, and P2Y1,2 and
      P2Y6 receptors. mESCs expressed P2X2,5 and P2X7 and P2Y1,2 and P2Y6 receptors.
      CONCLUSIONS AND IMPLICATIONS: GABAergic neurons derived from stem cells elevate
      [Ca2+]i predominantly via the activation of P2X2, P2X4 and P2Y1 receptors. This
      study shows that mESCs generate good models of neuronal function for in vitro
      pharmacological investigation.

PMID- 20050187
TI  - Differential effects of medroxyprogesterone acetate on thrombosis and
      atherosclerosis in mice.
AB  - BACKGROUND AND PURPOSE: The risk for cardiovascular events including venous and
      arterial disease and stroke is elevated after treatment with estrogen and
      medroxyprogesterone acetate (MPA) in postmenopausal women. Here, we have
      investigated the effect of MPA on arterial thrombosis and atherosclerosis in a
      murine model of atherosclerosis. EXPERIMENTAL APPROACH: Apolipoprotein E (ApoE)-/
      mice were bilaterally ovariectomized and treated with placebo, MPA (27.7 microg
      day(-1)) and MPA + 17-beta-oestradiol (E2; 1.1 microg day(-1)) for 90 days, on a
      Western-type diet. Thrombotic response was measured in a photothrombosis model,
      platelet activation by fluorescence activated cell sorting (FACS) analysis
      (CD62P) and thrombin generation by the endogenous thrombin potential (ETP).
      Furthermore, aortic plaque burden and aortic root plaque composition were
      determined. KEY RESULTS: MPA and MPA + E2-treated animals showed an aggravated
      thrombotic response shown by significantly reduced time to stable occlusion. The
      pro-thrombotic effect of MPA was paralleled by increased ETP whereas platelet
      activation was not affected. Furthermore, MPA + E2 reduced the number of cells
      positive for alpha-smooth muscle actin and increased hyaluronan in the plaque
      matrix. Interestingly, total plaque burden was reduced by MPA but unchanged by
      MPA + E2. CONCLUSION AND IMPLICATIONS: Long-term treatment with MPA and MPA + E2
      increased arterial thrombosis despite inhibitory effects of MPA on
      atherosclerosis in ApoE-deficient mice. Increased thrombin formation, reduced
      smooth muscle content and remodelling of non-collagenous plaque matrix may be
      involved in the pro-thrombotic effects. Thus, MPA exhibits differential effects
      on arterial thrombosis and on atherosclerosis.

PMID- 20050188
TI  - Novel effects mediated by bradykinin and  pharmacological characterization of
      bradykinin B2  receptor antagonism in human synovial fibroblasts.
AB  - BACKGROUND AND PURPOSE: Bradykinin (BK) and B2 receptors have been implicated in
      the pathophysiology of osteoarthritis (OA), and synovitis is one of its
      hallmarks. Here, the selective B2 receptor antagonists MEN16132 and icatibant
      have been pharmacologically characterized in human synovial cells. EXPERIMENTAL
      APPROACH: Radioligand and functional studies (inositol phosphate (IP)
      accumulation, interleukin (IL)-6 and IL-8 release) were performed in cultured
      synoviocytes. KEY RESULTS: [3H]-BK saturation studies indicated receptor density
      (Bmax) and K(d) values of 121,550 sites per cell and 1.14 nM respectively. In
      synoviocytes, MEN16132 (pK(I) 8.9) was threefold more potent than icatibant
      (pK(I) 8.4). Both antagonists showed competitive antagonism in the BK-induced IP
      assay (control EC50 0.45 nM), with pK(B) values of 9.9 (MEN16132) and 8.1
      (icatibant). 24h incubation with BK induced IL-6 (EC50 216 nM) and IL-8 (EC50 53
      nM) release. Both MEN16132 (IL-6: pIC50 8.1; IL-8: pIC50 8.4) and icatibant (IL
      6: pIC50 6.6; IL-8: pIC50 6.7) completely prevented this BK-induced release.
      Indomethacin did not affect the basal or the IL-6/IL-8 release induced by BK,
      whereas nordihydroguaiaretic acid decreased the basal release, although BK still
      increased IL-6 and IL-8 production. BK-induced IL-8 release was attenuated by
      inhibitors of phospholipase C (U73122), p38 (SB203580), JNK (SP600125), ERK 1/2
      (PD98059) MAPKs, phosphoinositide 3-kinase (LY294002), NF-kappaB (BAY-117085) and
      by the glucocorticoid dexamethasone. CONCLUSIONS AND IMPLICATIONS: Bradykinin via
      B2 receptors can participate in inflammatory events in synovitis. MEN16132 is a
      highly potent B2 receptor antagonist capable of blocking pro-inflammatory
      responses to BK evoked in human synoviocytes.

PMID- 20050190
TI  - Electrophysiological effects of anandamide on rat myocardium.
AB  - BACKGROUND AND PURPOSE: The endocannabinoid, anandamide, has anti-arrhythmic
      effects. The aim of the present study was to explore the electrophysiological
      effects of anandamide on rat myocardium. EXPERIMENTAL APPROACH: Evoked action
      potentials (APs) were recorded using intracellular recording technique in rat
      cardiac papillary muscles. In addition, L-type Ca2+ current was measured and
      analysed using whole-cell patch-clamp recording technique in isolated rat cardiac
      ventricular myocytes. KEY RESULTS: In cardiac papillary muscles, anandamide (1,
      10, 100 nM) decreased AP duration in a concentration-dependent manner.
      Furthermore, 100 nM anandamide decreased AP amplitude, overshoot and Vmax in
      partially depolarized papillary muscles. These effects were abolished by AM251
      (100 nM), a selective antagonist for CB1 receptors, but not AM630 (100 nM), a CB2
      receptor antagonist. Furthermore, an agonist of L-type Ca2+ channels, Bay K 8644
      (0.5 microM), a K+ channel blocker tetraethylammonium chloride (20 mM) and the
      nitric oxide synthase inhibitor L-NAME (1 mM) had no effect on anandamide-induced
      decrease in AP duration. In isolated ventricular myocytes, anandamide (1, 10, 100
      nM) decreased L-type Ca2+ current concentration-dependently, and shifted the
      current-voltage relationship curve of the Ca2+ current. Anandamide (100 nM)
      shifted the steady-state inactivation curve to the left and the recovery curve to
      the right. Blockade of CB1 receptors with AM251 (100 nM), but not CB2 receptors
      with AM630 (100 nM), eliminated the effect of anandamide on L-type Ca2+ currents.
      CONCLUSIONS AND IMPLICATIONS: These data suggest that anandamide suppressed AP
      and L-type Ca2+ current in cardiac myocytes through CB1 receptors.

PMID- 20050191
TI  - Cardiovascular genetics in Iceland: an investment  to bank on?

PMID- 20050189
TI  - Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke, seizures and
      sensorimotor gating deficit.
AB  - BACKGROUND AND PURPOSE: Abnormal glutamatergic activity is implicated in
      neurologic and neuropsychiatric disorders. Selective glutamate receptor
      antagonists were highly effective in animal models of stroke and seizures but
      failed in further clinical development because of serious side effects, including
      an almost complete set of symptoms of schizophrenia. Therefore, the novel
      polyvalent glutamatergic agent 3,5-dibromo-L-phenylalanine (3,5-DBr-L-Phe) was
      studied in rat models of stroke, seizures and sensorimotor gating deficit.
      EXPERIMENTAL APPROACH: 3,5-DBr-L-Phe was administered intraperitoneally as three
      boluses after intracerebral injection of endothelin-1 (ET-1) adjacent to the
      middle cerebral artery to cause brain injury (a model of stroke). 3,5-DBr-L-Phe
      was also given as a single bolus prior to pentylenetetrazole (PTZ) injection to
      induce seizures or prior to the administration of the N-methyl-D-aspartate (NMDA)
      receptor antagonist dizocilpine (MK-801) to cause disruption of prepulse
      inhibition (PPI) of startle (sensorimotor gating deficit). KEY RESULTS: Brain
      damage caused by ET-1 was reduced by 52%, which is comparable with the effects of
      MK-801 in this model as reported by others. 3,5-DBr-L-Phe significantly reduced
      seizures induced by PTZ without the significant effects on arterial blood
      pressure and heart rate normally caused by NMDA antagonists. 3,5-DBr-L-Phe
      prevented the disruption of PPI measured 3 days after the administration of ET-1.
      3,5-DBr-L-Phe also eliminated sensorimotor gating deficit caused by MK-801.
      CONCLUSION AND IMPLICATIONS: The pharmacological profile of 3,5-DBr-L-Phe might
      be beneficial not only for developing a therapy for the neurological and
      cognitive symptoms of stroke and seizures but also for some neuropsychiatric
      disorders.

PMID- 20050193
TI  - Pioneering in cardiology. Development of the artificial pacemaker.

PMID- 20050194
TI  - Distinct effects of CGRP on typical and atypical  smooth muscle cells involved in
      generating  spontaneous contractions in the mouse renal pelvis.
AB  - BACKGROUND AND PURPOSE: We investigated the cellular mechanisms underlying
      spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene
      related peptide (CGRP). EXPERIMENTAL APPROACH: Spontaneous contractions, action
      potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs
      and ATSMCs) within the renal pelvis wall were recorded separately using tension
      and intracellular microelectrode recording techniques and Fluo-4 Ca2+ imaging.
      Immunohistochemical and electron microscopic studies were also carried out. KEY
      RESULTS: Bundles of CGRP containing transient receptor potential cation channel,
      subfamily V, member 1-positive sensory nerves were situated near both TSMCs and
      ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and
      duration of spontaneous phasic contractions, action potentials and Ca2+
      transients in TSMCs. CGRP and agents increasing internal cyclic adenosine
      monophosphate (cAMP) mimicked the nerve-mediated modulation of TSMC activity and
      suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or
      cAMP stimulators was blocked by glibenclamide, while their negative chronotropic
      effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but
      inhibited ATSMC Ca2+ transients, while both 5-hydroxydecanoate and diazoxide, a
      blocker and opener of mitochondrial ATP-sensitive K+ channels, respectively,
      reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of
      mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous
      excitation of TSMCs. CONCLUSIONS AND IMPLICATIONS: The negative chronotropic
      effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather
      than opening of plasmalemmal ATP-sensitive K+ channels in TSMCs. The positive
      inotropic effects of CGRP may derive from activation of TSMC L-type Ca2+
      channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in
      generating Ca2+ transients.

PMID- 20050195
TI  - The chemokine receptor antagonist, TAK-779, decreased experimental autoimmune
      encephalomyelitis by reducing inflammatory cell migration into the central
      nervous system, without affecting T cell function.
AB  - BACKGROUND AND PURPOSE: The C-C chemokine receptor CCR5, and the C-X-C chemokine
      receptor CXCR3 are involved in the regulation of T cell-mediated immune
      responses, and in the migration and activation of these cells. To determine
      whether blockade of these chemokine receptors modulated inflammatory responses in
      the central nervous sytem (CNS), we investigated the effect of a non-peptide
      chemokine receptor antagonist, TAK-779, in mice with experimental autoimmune
      encephalomyelitis (EAE). EXPERIMENTAL APPROACH: EAE was induced by immunization
      of C57BL/6 mice with myelin oligodendrocyte glycoprotein (MOG) 35-55. TAK-779 was
      injected s.c. once a day after immunization. Disease incidence and severity (over
      3 weeks) were monitored by histopathological evaluation and FACS assay of
      inflammatory cells infiltrating into the spinal cord, polymerase chain reaction
      quantification of mRNA expression, assay of T cell proliferation, by [3H]
      thymidine incorporation and cytokine production by enzyme-linked immunosorbent
      assay. KEY RESULTS: Treatment with TAK-779 reduced incidence and severity of EAE.
      It strongly inhibited migration of CXCR3/CCR5 bearing CD4+, CD8+ and CD11b+
      leukocytes to the CNS. TAK-779 did not reduce proliferation of anti-MOG T cells,
      the production of IFN-gamma by T cells or CXCR3 expression on T cells. In
      addition, TAK-779 did not affect production of IL-12 by antigen-presenting cells,
      CCR5 induction on T cells and the potential of MOG-specific T cells to transfer
      EAE. CONCLUSIONS AND IMPLICATIONS: TAK-779 restricted the development of MOG
      induced EAE. This effect involved reduced migration of inflammatory cells into
      the CNS without affecting responses of anti-MOG T cells or the ability of MOG
      specific T cells to transfer EAE.

PMID- 20050196
TI  - Ticagrelor versus clopidogrel in acute coronary syndromes.

PMID- 20050197
TI  - Ticagrelor versus clopidogrel in acute coronary syndromes.

PMID- 20050198
TI  - Ticagrelor versus clopidogrel in acute coronary syndromes.

PMID- 20050199
TI  - US targets disease prevention in health reforms.

PMID- 20050200
TI  - Palifermin: anaphylaxis, oedema and hyperpigmentation. Sucking ice is safer for
      preventing oral mucositis.

PMID- 20050201
TI  - Bisphosphonates: atypical fractures. Femur most often involved.

PMID- 20050202
TI  - SOGC CLINICAL PRACTICE GUIDELINE: guidelines for the management of vasa previa.
AB  - OBJECTIVES: To describe the etiology of vasa previa and the risk factors and
      associated condition, to identify the various clinical presentations of vasa
      previa, to describe the ultrasound tools used in its diagnosis, and to describe
      the management of vasa previa. OUTCOMES: Reduction of perinatal mortality, short
      term neonatal morbidity, long-term infant morbidity, and short-term and long-term
      maternal morbidity and mortality. EVIDENCE: Published literature on randomized
      trials prospective cohort studies, and selected retrospective cohort studies was
      retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane
      Library, using appropriate controlled vocabulary (e.g., selected epidemiological
      studies comparing delivery by Caesarean section with vaginal delivery studies
      comparing outcomes when vasa previa is diagnosed antenatally vs.intrapartum) and
      key words (e.g. vasa previa). Results were restricted to systematic reviews,
      randomized control trials/controlled clinical trials, and observational studies.
      Searches were updated on a regular basis and incorporated into the guideline to
      October 1, 2008. Grey (unpublished) literature was identified through searching
      the websites of health technology assessment and health technology assessment
      related agencies,clinical practice guideline collections, clinical trial
      registries, and from national and international medical specialty societies.
      VALUES: The evidence collected was reviewed by the Diagnostic Imaging Committee
      and the Maternal Fetal Medicine Committee of the Society of Obstetricians and
      Gynaecologists of Canada (SOGC) and quantified using the evaluation of evidence
      guidelines developed by the Canadian Task Force on Preventive Health Care.
      BENEFITS, HARMS, AND COSTS: The benefit expected from this guideline is
      facilitation of optimal and uniform care for pregnancies complicated by vasa
      previa. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada.

PMID- 20050203
TI  - Tacrolimus: confusion between products. Unnecessary line extension.

PMID- 20050204
TI  - Celiac disease affects older adults.  Finnish researchers have discovered that
      sprue, once thought to be a disease of the young, also afflicts people over 55.

PMID- 20050205
TI  - Spinal fracture treatment raises questions.  Vertebroplasty, a widely used
      treatment for osteoporotic spinal fractures, may be no better than placebo.

PMID- 20050206
TI  - 4 Healthy lifestyle factors help ward off chronic disease. Diet, exercise, low
      body mass index and not smoking can reduce the incidence of heart disease,
      diabetes, stroke and cancer.

PMID- 20050207
TI  - New screening methods for breast cancer.  Techniques are evolving to address
      issues of inaccuracy and discomfort.

PMID- 20050208
TI  - Binge drinking is a problem for older adults, too.  More than five drinks at a
      time can lead to accidents, falls, and negative interactions with medications.

PMID- 20050210
TI  - What's a "normal" resting heart rate?  Can it change as a result of age or
      medical conditions such as high blood pressure?

PMID- 20050209
TI  - My doctor recommended I take methotrexate to relieve the pain of the rheumatoid
      arthritis I have in my shoulder. But I've heard that methotrexate can cause liver
      problems. How will I know if I'm developing liver problems?

PMID- 20050211
TI  - Why are omega-3 fatty acids good for you, and what are the best sources other
      than fish?

PMID- 20050212
TI  - Treatment of lung cancer.

PMID- 20050213
TI  - Treatment of lung cancer.

PMID- 20050214
TI  - Treatment of lung cancer.

PMID- 20050215
TI  - Asymptomatic reactivation of JC virus in patients treated with  natalizumab.

PMID- 20050216
TI  - Asymptomatic reactivation of JC virus in patients treated with natalizumab.

PMID- 20050217
TI  - Coronary calcium screening.

PMID- 20050218
TI  - Methods for the analysis of melamine and related compounds in foods: a review.
AB  - In recent years, two adulteration incidents concerning the addition of melamine
      (MEL) and related compounds to dairy products and vegetable proteins have
      occurred in China. These episodes prompted numerous governmental and private
      laboratories to develop or implement methods for the analysis of a wide variety
      of food products for MEL and related compounds, including cyanuric acid,
      ammeline, and ammelide. Methods have been developed for both screening and
      quantitation purposes; procedures used in the methods range from sensitive
      hyphenated chromatographic-mass spectrometric techniques to immunoselective
      assays. Various issues are encountered during the analysis of MEL and related
      compounds in food products. These issues include contamination, matrix effects,
      and analyte instability, and their severity varies according to the method used,
      and matrices and analytes examined.

PMID- 20050219
TI  - Animal genitalia in evolution. Preface.

PMID- 20050220
TI  - Intimate partner violence.

PMID- 20050221
TI  - Chest X-ray quiz.

PMID- 20050222
TI  - Tuberculosis + HIV = a complex calculus.

PMID- 20050223
TI  - What needs to be done in contingent  valuation: have Smith and Sach missed  the
      boat?

PMID- 20050224
TI  - Contingent valuation studies and health policy.

PMID- 20050225
TI  - Contingent valuation: has the debate begun?

PMID- 20050226
TI  - Histomorphometric differences between the left and right internal thoracic
      arteries in humans.

PMID- 20050227
TI  - The fulfillment of a desire.

PMID- 20050228
TI  - Presidential address. Reflections on: our planet and its life, origins, and
      futures.

PMID- 20050229
TI  - Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of
      anaplastic pancreatic carcinoma: a single-center experience.
AB  - OBJECTIVES: Anaplastic carcinoma of the pancreas (ACP) is an aggressive variant
      of ductal adenocarcinoma. The aim of this study was to describe a single-center
      experience with the use of endoscopic ultrasound (EUS) with or without fine
      needle aspiration (FNA) for the diagnosis of ACP. METHODS: The cytology and
      surgical pathology databases were searched for a diagnosis of ACP between 1992
      and 2008. Demographic, clinical,surgical, radiographic, pathological, and EUS
      data were abstracted. RESULTS: Thirteen patients with ACP were identified, which
      represented 0.8% of all pancreatic cancers diagnosed during the study period. Six
      of 13 patients had EUS. Features of these 6 tumors: median diameter of 42 mm
      (range, 20-100 mm), hypoechoic (n = 6), solid (n = 3) or mixed solid and cystic
      (n = 3), heterogeneous (n = 5) or homogeneous (n = 1),and well defined (n = 2) or
      poorly defined (n = 4) borders. Five underwent EUS-FNA of a pancreatic mass, and
      cytology demonstrated ACP in 4 and ductal adenocarcinoma in 1. The diagnosis of
      ACP was confirmed after surgical resection in 2 of these 5, including one in whom
      cytology demonstrated only adenocarcinoma. The sixth patient had EUS without FNA,
      and surgical pathology after distal pancreatectomy found ACP. CONCLUSIONS:
      Anaplastic carcinoma of the pancreas has variable endosonographic features.
      Endoscopic ultrasound-FNA may assist in the cytological diagnosis of these
      tumors.

PMID- 20050230
TI  - Chronic pancreatitis is associated with hyperhomocysteinemia and derangements in
      transsulfuration and transmethylation pathways.
AB  - OBJECTIVES: Homocysteine has been implicated in vascular dysfunction and
      thrombosis, as well as inflammatory conditions. This study was aimed to find out
      whether chronic pancreatitis (CP) is associated with hyperhomocysteinemia and
      derangements of transmethylation and transsulfuration pathways. METHODS: We
      estimated homocysteine and its metabolites in 45 alcoholic CP patients, 45
      tropical CP patients, and 48 healthy controls. RESULTS: Significant increases in
      plasma total homocysteine and decreases in red blood cell folate, reduced
      glutathione, plasma methionine, cysteine, and urinary inorganic
      sulfate/creatinine ratio were observed in both alcoholic and tropical CP patients
      in comparison with healthy controls. Red blood cell glutathione and plasma
      cysteine levels were significantly lower in alcoholic than in tropical CP
      patients. However, plasma vitamin B12 levels were comparable between CP patients
      and controls. No significant differences in these parameters were observed
      between diabetic patients and nondiabetic patients. Multivariate regression
      analysis showed a significant negative correlation between homocysteine and
      folate (r = -0.415, P = 0.001) and a positive correlation between glutathione and
      cysteine levels (r = 0.37, P = 0.003). CONCLUSIONS: Chronic pancreatitis is
      associated with hyperhomocysteinemia and derangements in transmethylation and
      transsulfuration pathways. Low folate levels observed in these patients seem to
      have a key role in this derangement.

PMID- 20050231
TI  - This is a test. Exams for governance boards on quality measures could be a way to
      improve care, accountability in hospitals.
AB  - Hospital board members have little or no training on quality or safety issues and
      a spotty record of oversight in those areas, a new study published by Health
      Affairs has found. Many are convinced that boards have a big role to play in
      improving quality and safety, and that by focusing on those issues, they can
      spark change. "I think it's a question of calling it out. It's all laid out and
      everybody sees it", says former MedStar Chairman E. F. Shaw Wilgis, left.

PMID- 20050232
TI  - In or out. CMS Web site to report outpatient results.

PMID- 20050233
TI  - Between the lines. Hospital profits plunged in '08, but for different reasons
      than expected: AHA.

PMID- 20050234
TI  - The house's SGR dilemma. Senate unlikely to cooperate on bill docs want badly.

PMID- 20050235
TI  - Wellness incentives under fire. American Cancer Society among the detractors.

PMID- 20050236
TI  - Not so fast. FTC decided deal bad for competition: Scott & White.

PMID- 20050237
TI  - Beyond just doctors. Payments to physicians always arouse interest, but others
      deserve scrutiny too.

PMID- 20050238
TI  - Squash the bugs...and your hospital reaps the bottom-line benefits.

PMID- 20050239
TI  - Laboring to unite. After years of feuding and raiding each other's ranks, more
      healthcare unions are joining hands so they can work together on a common pro
      labor agenda.

PMID- 20050240
TI  - The cost of murder. Anti-violence groups, hospitals work to try and stop
      homicides, which have negative impacts on both the community and bottom lines.
AB  - The brutal toll of homicide in their communities has some hospitals working with
      anti-violence groups to halt the slaughter by trying to stop retaliation. Talking
      to victims after an attack is "really this golden window of opportunity, when
      they're open to change", says Marla Becker, left, of Youth Alive.

PMID- 20050241
TI  - Anti-violent beginnings. Hospital-based programs among the options.

PMID- 20050242
TI  - A break, then debate. Abortion, public option still divide reform efforts.

PMID- 20050243
TI  - Bolstering COBRA. Some senators propose extensions to the subsidy.

PMID- 20050245
TI  - IHS' billing under fire. Baucus urges changes in wake of GAO report.

PMID- 20050244
TI  - RAC expansion questioned. Providers not sure of need for more audits outlined in
      Senate bill.

PMID- 20050246
TI  - Fall rush. Markets cool as not-for-profits seek low rates.

PMID- 20050247
TI  - Testing the system. Don't turn task force's mammogram guidelines into political
      football.

PMID- 20050248
TI  - While reform percolates. S.C. Blues, docs team up for medical home pilot.

PMID- 20050264
TI  - Considerations to improve functional annotations in biological databases.
AB  - Despite the great effort to design efficient systems allowing the electronic
      indexation of information concerning genes, proteins, structures, and
      interactions published daily in scientific journals, some problems are still
      observed in specific tasks such as functional annotation. The annotation of
      function is a critical issue for bioinformatic routines, such as for instance, in
      functional genomics and the further prediction of unknown protein function, which
      are highly dependent of the quality of existing annotations. Some information
      management systems evolve to efficiently incorporate information from large-scale
      projects, but often, annotation of single records from the literature is
      difficult and slow. In this short report, functional characterizations of a
      representative sample of the entire set of uncharacterized proteins from
      Escherichia coli K12 was compiled from Swiss-Prot, PubMed, and EcoCyc and
      demonstrate a functional annotation deficit in biological databases. Some issues
      are postulated as causes of the lack of annotation, and different solutions are
      evaluated and proposed to avoid them. The hope is that as a consequence of these
      observations, there will be new impetus to improve the speed and quality of
      functional annotation and ultimately provide updated, reliable information to the
      scientific community.

PMID- 20050265
TI  - Variety of audiologic manifestations in patients with superior semicircular canal
      dehiscence.
AB  - OBJECTIVE: To present diverse symptoms, signs, and findings on diagnostic tests
      of 11 patients with superior semicircular canal dehiscence (SSCD) syndrome and
      surgical treatments for dehiscence of 3 patients. STUDY DESIGN: Retrospective
      case review. SETTING: Tertiary neurotologic and audiologic center. PATIENTS:
      Patients with SSCD documented by history, physical examination, vestibular
      function testing, and high-resolution computed tomographic scans. INTERVENTION:
      Two patients underwent surgical procedures through middle fossa approach, and 1
      patient underwent transmastoid repair. The rest underwent conservative
      treatments. RESULTS: Eleven patients were identified as SSCD. The variety of
      clinical manifestations, including 1) hearing presentations: mix hearing loss (4
      of 11), conductive hearing loss (3 of 11), profound sensorineural hearing loss (2
      of 11), and normal hearing (2 of 11); 2) vestibular manifestations: chronic
      disequilibrium (8 of 11), Tullio phenomenon (7 of 11), Hennebert sign (8 of 11),
      tinnitus (3 of 11), and autophony (3 of 11); and 3) accompanying disorders:
      encephalomeningocele (1 of 11). Abnormal nystagmus was identified in 3 patients.
      Dehiscence of bone overlying superior semicircular canal was confirmed by high
      resolution computed tomographic scan in all cases. Three patients underwent
      operative management. (2 through the middle fossa approach and 1 through a
      transmastoid repair). CONCLUSION: Superior semicircular canal dehiscence
      demonstrates diverse and complex clinical features. Tegmental or petrosal bone
      rarefaction or mild dehiscences can be a harbinger or an aggressive cause of
      developing SSCD. No correlation was observed between the size of dehiscence and
      the severity of vestibular symptoms or the degree of hearing loss. Surgical
      repair of dehiscence can relieve symptoms with low morbidity.

PMID- 20050266
TI  - A summary of the literature on global hearing impairment: current status and
      priorities for action.
AB  - BACKGROUND: Hearing loss (HL) and deafness are global issues that affect at least
      278 million people worldwide. Two thirds of the people who have HL worldwide live
      in developing countries. Importantly, it is estimated that 50% of this HL can be
      prevented. In developing countries, funding for prevention, early detection, and
      rehabilitative programs is severely limited, and therefore, agencies must compete
      against priorities to treat life-threatening, pandemic diseases such as human
      immunodeficiency virus, malaria, and tuberculosis. Delays in diagnosis are
      common, and social attitudes, local customs, and cultural bias are contributing
      factors. OBJECTIVE: The purpose of this review is to gain an understanding of the
      prevalence of HL in the developing world and to focus attention on the growing
      need for both prevention and effective treatment programs. A second goal is to
      use this information to suggest priorities and approaches to address these
      problems worldwide. DATA SOURCES: The data were compiled from a review of the
      literature on the global impacts of hearing impairment and recently published
      reports on the prevalence and cause of hearing impairment in developing nations.
      CONCLUSION: The high prevalence of HL in the developing world is due to a variety
      of factors, including lack of widespread comprehensive immunization programs and
      other medical care, and inadequate funds for intervention once HL is identified.
      International organizations, governments, and nongovernment organizations have
      many opportunities to prevent and treat HL through cost-effective means.

PMID- 20050267
TI  - Cochlear implantation in postmeningitic deafness.
AB  - OBJECTIVES/HYPOTHESIS: To propose guidelines in the management of a profound
      bilateral sensorineural hearing loss after bacterial meningitis. STUDY DESIGN:
      Retrospective chart review. PATIENTS: All 40 postmeningitic cochlear implantation
      surgeries performed between August 1987 and April 2007. METHODS: Descriptive
      analysis of data on the cause of meningitis, preoperative imaging evaluation, age
      at implantation, time elapsed between meningitis and implantation, and relevant
      surgical findings. RESULTS: Twenty-seven children and 13 adults with
      postmeningitic deafness were implanted. Mean age was 3 years 8 months for the
      children and 44 years and 10 months for the adults. The mean time delay between
      meningitis and surgery was 2 years 1 month for children and 28 years for adults.
      Eighteen children (67%) were implanted within a year. Labyrinthitis ossificans
      was evidenced at surgery in 62% of patients. Intraoperative cochlear ossification
      was classified according to the scale described by Smullen and Balkany (2005).
      Stage II ossification was seen in 3 patients within 49 days, with 1 of them as
      soon as 21 days. There was a partial insertion in 9 patients secondary to
      ossification. Open-set speech discrimination was achieved by 37% of the children
      (10 of 27) and 23% of the adults (3 of 13). CONCLUSION: We recommend early
      cochlear implantation for patients with bilateral profound deafness secondary to
      meningitis.

PMID- 20050268
TI  - Improvement in autophony symptoms after superior canal dehiscence repair.
AB  - OBJECTIVE: Autophony, or the unusually loud or disturbing sound of a patient's
      own voice, can be a prominent and disabling symptom of superior canal dehiscence
      (SCD) syndrome. The current study measures autophony symptoms before and after
      SCD plugging to quantify the benefits of surgery. STUDY DESIGN: Patients
      undergoing SCD plugging between September 2007 and October 2008 completed a
      questionnaire before and 3 months after surgery. The questionnaire consisted of
      26 statements to assess the disability caused by the sound of the patient's own
      voice. Patients graded each item on a scale from 0 (never) to 4 (almost always)
      to how often they noted a symptom or experience. Typical statements included
      "hearing my voice has interfered with my ability to work" and "hearing my voice
      has caused me to avoid social situations." An autophony index (AI) was generated
      to grade patient symptoms. SETTING: Tertiary referral center. PATIENTS: Nineteen
      adults with SCD. INTERVENTION: Superior canal dehiscence plugging via a middle
      fossa approach. OUTCOME MEASURES: Change in AI. RESULTS: Preoperatively, the mean
      AI was 42 +/- 27 (mean +/- SD; range, 0-86; 1 patient had no autophony symptoms).
      Postoperative AI decreased 89% to 9 +/- 22, a significant (p < 0.01) decline. Of
      the 18 patients with preoperative autophony, 13 had complete postoperative
      resolution. In 3 remaining patients, the AI decreased but did not resolve. One of
      these had bilateral SCD with contralateral autophony. One patient's mild
      autophony remained unchanged, and another patient with coexisting patulous
      eustachian tube AI increased after SCD plugging. CONCLUSION: In patients with
      significant autophony symptoms, SCD plugging improved 94% of patients. A simple 5
      item AI is provided that will be useful in grading autophony symptoms.

PMID- 20050269
TI  - From the editors.

PMID- 20050270
TI  - Systems biology: Small genome, complex regulation.

PMID- 20050271
TI  - Human disease: Edges, nodes and networks.

PMID- 20050272
TI  - Bioinformatics: SNPs while you wait.

PMID- 20050273
TI  - Regulatory elements: A metamorphosis in synthesis.

PMID- 20050274
TI  - Small RNAs: Sorting the strands.

PMID- 20050275
TI  - Genomics: Maize looks set to amaze.

PMID- 20050276
TI  - Cancer: Small losses, big gains with microRNAs.

PMID- 20050277
TI  - Population genetics: SNPs that come in threes.

PMID- 20050278
TI  - Stop taking warfarin? No way! Comment.

PMID- 20050279
TI  - Adverse outcomes of labour in public and private hospitals in Australia. Comment.

PMID- 20050280
TI  - Adverse outcomes of labour in public and private hospitals in Australia. Comment.

PMID- 20050281
TI  - Patterns of mortality in Indigenous adults in the Northern Territory, 1998-2003.
      Comment.

PMID- 20050282
TI  - [Requirements for analytical quality: use of the concept of biological
      variation].
AB  - By using a clinical biochemistry laboratory as an example, the authors show how
      the analytical quality system practically operates. The advantages of using a
      three-level model for analytical quality requirements on the basis of biological
      variations in analytes are discussed. Only does the use of a few normative
      documents present a possibility of creating an adequate quality system in a
      specific laboratory. The long-term coefficient of analytical variation is the
      most important characteristic of analytical quality and a necessary component of
      the day-to-day work of the laboratory. The level of quality is shown for 27
      analytes. Despite the fact that the laboratory uses the same analytical systems
      as in the world, the level of analytical quality has turned out to be lower than
      in the best laboratories of Europe.

PMID- 20050283
TI  - [Some biochemical parameters in the placenta in discoordinated and powerless
      labors].
AB  - A number of biochemical parameters (total nitrites and nitrates (NO(x)), cyclic
      guanosine monophosphate (cGMP), nitrotyrosine, medium-weight molecules (MCM) in
      the placenta were determined in women with gestosis during discoordinated and
      powerless labor. Thirty placentas (10 placentas from parturients after
      discoordinated labor, 10 from those after powerless labor, 10 placentas as a
      control group) were examined. Changes in the parameters under study were found to
      result in the development of nitroxide and oxidant stresses and endotoxicosis.
      The biochemical parameters should be considered as placental criteria for the
      differential diagnosis of labor anomalies in gestosis, such as powerless and
      discoordinated labors.

PMID- 20050284
TI  - [Discriminant function analysis in the assessment of laboratory values in
      children with food allergy in acute viral hepatitis B].
AB  - The purpose of this investigation was to define the impact of food allergy (FA)
      in children on the time of normalization of a complex of the indices of a blood
      biochemical test for bilirubin and enzymes in acute viral hepatitis B (VHB).
      Discriminant function analysis through the mathematical expression of the
      combined influence of variables in a complex of the values of a blood biochemical
      test for bilirubin and enzymes in children with FA who had experienced a mild
      icteric form of VHB showed the absence of their normalization throughout one-year
      follow-up after hospital discharge. Among the examinees, there were twenty-five 3
      14-year-old children with FA who had experienced a mild icteric form of VHB.
      About half of them were girls (44%). Blood biochemical tests for bilirubin and
      enzymes were carried out in both the acute stage of the disease and in
      convalescence at least 5 times 1, 3, 6, 9, and 12 months after their hospital
      discharge. The similar laboratory tests (blood biochemical tests for bilirubin
      and enzymes, marker spectrum to hepatitis virus) were performed in 20 healthy
      children (a control group).

PMID- 20050285
TI  - [Evaluation of D-dimer in outpatients: clinical value and specific features].
AB  - D-dimer as an activation marker of coagulation and fibrinolysis is a recognized
      diagnostic criterion of deep vein thrombosis, pulmonary thromboembolism, and
      disseminated intravascular coagulation. In recent years, this laboratory test has
      been most frequently used for other purposes: to detect the activation of
      coagulation, to predict the course of diseases, and to determine the duration of
      anticoagulant therapy. Our investigation examined 1514 D-dimer measurements in
      1370 outpatients without acute abnormalities, including 72 patients receiving
      warfarin and 32 patients after myocardial revascularization. 36.1% of cases were
      found to have values of more than 0.5 mkg/ml. Adequate anticoagulant therapy (INR
      2-3) caused a reduction in the level of D-dimer that is an important additional
      laboratory test for the evaluation of antithrombotic defense. Further
      investigations are needed to determine cutoff values for various clinical
      situations.

PMID- 20050286
TI  - A bridge to somewhere.

PMID- 20050287
TI  - Cholesterol metabolism and transport in the pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting
      millions of people worldwide. Apart from age, the major risk factor identified so
      far for the sporadic form of AD is possession of the epsilon4 allele of
      apolipoprotein E (APOE), which is also a risk factor for coronary artery disease
      (CAD). Other apolipoproteins known to play an important role in CAD such as
      apolipoprotein B are now gaining attention for their role in AD as well. AD and
      CAD share other risk factors, such as altered cholesterol levels, particularly
      high levels of low density lipoproteins together with low levels of high density
      lipoproteins. Statins--drugs that have been used to lower cholesterol levels in
      CAD, have been shown to protect against AD, although the protective mechanism(s)
      involved are still under debate. Enzymatic production of the beta amyloid
      peptide, the peptide thought to play a major role in AD pathogenesis, is affected
      by membrane cholesterol levels. In addition, polymorphisms in several proteins
      and enzymes involved in cholesterol and lipoprotein transport and metabolism have
      been linked to risk of AD. Taken together, these findings provide strong evidence
      that changes in cholesterol metabolism are intimately involved in AD pathogenic
      processes. This paper reviews cholesterol metabolism and transport, as well as
      those aspects of cholesterol metabolism that have been linked with AD.

PMID- 20050288
TI  - Cannabinoids prevent the opposite regulation of astroglial connexin43
      hemichannels and gap junction channels induced by pro-inflammatory treatments.
AB  - Brain injuries as well as neurodegenerative diseases, are associated with neuro
      inflammation characterized by astroglial and microglial activation and/or
      proliferation. Recently, we reported that lipopolysaccharide (LPS)-activation of
      microglia inhibits junctional channels and promotes hemichannels, two connexin43
      functions in astrocytes. This opposite regulation is mediated by two pro
      inflammatory cytokines, interleukin-1 beta and tumor necrosis factor-alpha,
      released from activated microglia. Because cannabinoids (CBs) have anti
      inflammatory properties and their receptors are expressed by glial cells, we
      investigated on primary cortical cultures the effects of CB agonists,
      methanandamide and synthetic CBs on (i) cytokines released from LPS-activated
      microglia and (ii) connexin43 functions in astrocytes subjected to pro
      inflammatory treatments. We observed that CBs inhibited the LPS-induced release
      of interleukin-1 beta and tumor necrosis factor-alpha from microglia. Moreover,
      the connexin43 dual regulation evoked by the pro-inflammatory treatments, was
      prevented by CB treatments. Pharmacological characterizations of CB actions on
      astrocytic connexin43 channels revealed that these effects were mainly mediated
      through CB1 receptors activation, although non-CB1/CB2 receptors seemed to
      mediate the action of the methanandamide. Altogether these data demonstrate that
      in inflammatory situations CBs exert, through the activation of different sub
      types of glial CB receptors, a regulation on two functions of connexin43 channels
      in astrocytes known to be involved in neuron survival.

PMID- 20050289
TI  - Amyloid beta serves as an NGF-like neurotrophic factor or acts as a NGF
      antagonist depending on its concentration.
AB  - In the nervous system, both the shape and connectivity of neurons are strongly
      influenced by soluble, extracellular factors. Indeed, we recently demonstrated
      that after binding to p75(NTR), the common neurotrophin receptor, nerve growth
      factor (NGF) controls the morphology and connectivity of cultured mouse
      hippocampal neurons by encouraging the production of fewer yet longer dendrites,
      and by augmenting GABAergic connectivity. These effects of NGF are mediated by
      the differential expression of Enhancer-of-split 1/5 homologs and neurogenin 3.
      Amyloid beta (Abeta), a pathogenic agent in Alzheimer's disease (AD) is known to
      bind to p75(NTR), hence we studied its influence on cultured hippocampal neurons.
      At 800 nM, Abeta(1-40) prevents NGF-induced activation of NF-kappaB and
      consequently, it depresses the expression of Enhancer-of-split 1. Thus, at this
      concentration, the effect of Abeta on neurons is antagonistic to those provoked
      by NGF and accordingly, neurons sprout more yet shorter dendrites and their
      GABAergic input decreases. In contrast, at lower concentration, 20 nM, the
      amyloid induces cellular effects similar to those induced by NGF, both in terms
      of gene expression, neuronal morphology, and GABAergic connectivity. Our results
      demonstrate that Abeta may act as a neurotrophic factor that mimics the activity
      of NGF. However, at higher concentrations, the amyloid behaves as an antagonist
      of NGF, contributing to the advent of AD.

PMID- 20050290
TI  - Development and validation of nail psoriasis quality of life  scale (NPQ10).
AB  - BACKGROUND: The chronic and treatment-resistant nature of nail psoriasis affects
      patients' lives not only physically but also psychologically. Although there are
      scoring systems available for disease severity, there is as yet no scale to
      evaluate the impact of this condition upon the patients' quality of life.
      OBJECTIVES: This study aims to develop and validate a quality of life scale
      specifically for nail psoriasis. METHODS: A questionnaire was developed during a
      study conducted in France between 2004 and 2005. With the cooperation of
      l'Association Pour la Lutte Contre le Psoriasis, the questionnaire was sent to a
      random sample of 4000 of its 17,000 members. RESULTS: The response rate was 33%.
      Of the 1309 questionnaires returned, 795 showed the presence of nail psoriasis
      and these were eligible. The scale score is obtained by adding together the
      responses to the 10 questionnaire items and the result is expressed as a
      percentage. The value of the score obtained is proportional to the functional
      difficulty experienced. The determination of Cronbach's a coefficient and a
      Principal Component Factor Analysis show, respectively, very good internal
      consistency and the unidimensional nature of the scale. Test-retest results on 15
      patients showed good reproducibility. Results were validated with reference to
      the Dermatology Life Quality Index. In this study, the NPQ10 score is
      significantly influenced by gender (women have a higher score) and by the
      duration of psoriasis (recent onset implies greater functional difficulty).
      Finally, the score is much higher when the nail psoriasis affects both the hands
      and the feet. CONCLUSION: This study confirms a change in the quality of life of
      patients who have nail psoriasis. The NPQ10 scale, specific to this condition, is
      simple to use and has the attributes needed in a quality of life scale. The scale
      must now be tested in longitudinal studies (such as clinical trials) to confirm
      its ability to measure a change in status.

PMID- 20050291
TI  - Reversible posterior leukoencephalopathy: a possible threat for psoriatic
      patients treated with biological agents.

PMID- 20050292
TI  - Multiple target-like pigmented   nevi: an inverse halo-nevus   phenomenon.

PMID- 20050293
TI  - [Simultaneous injection of lidocaine improves predictability of effect of
      botulinum toxin].
AB  - Injection of botulinum toxin A is a common procedure in Otorhinolaryngology,
      Ophtalmology and Neurolgy. Recently botulinum toxin treatment has been described
      to improve woundhealing after facial injuries. The lack of immediate
      predictibility of the ensuing paralytic effect is one of the daily challenges of
      botulinum toxin injections. In the present report we describe the simultaneous
      injection of botulinum toxin and lidocaine with the purpose to gain immediate
      feed back of the treatment effect. Furthermore we recommend the addition of
      adrenalin to reduce possible systemical toxin circulation.

PMID- 20050294
TI  - A case of pemphigus   herpetiformis with absence   of antibodies to desmogleins  
      1 and 3.

PMID- 20050295
TI  - Left ventricular assist for pediatric patients with dilated cardiomyopathy using
      the Medos VAD cannula and a centrifugal pump.
AB  - Ventricular assist devices for small pediatric patients are expensive and
      commercially unavailable in Taiwan. We used the Medos ventricular assist device
      cannula (Medos, Aachen, Germany) and a centrifugal pump to support pediatric
      patients with dilated cardiomyopathy and decompensated heart failure. From
      January 2007 to December 2008, three pediatric patients with dilated
      cardiomyopathy were supported using a centrifugal pump as the left ventricular
      assist device. The Medos arterial cannula was sutured to the ascending aorta, and
      the Apex cannula was fixed into the left ventricular apex. When the patient was
      weaned off of cardiopulmonary bypass, the left ventricular assist device pump was
      started. The pump flow was gradually titrated according to the filling status of
      the left ventricle. All the left ventricular assist devices were successfully
      implanted and functioned well. Two patients on extracorporeal membrane
      oxygenation had severe lung edema before left ventricular assist device
      implantation. Both patients required extracorporeal membrane oxygenation for the
      postoperative period until the pulmonary edema was resolved. Among the three
      patients, two successfully bridged to heart transplantation after support for 6
      and 11 days, respectively. The first patient (10 kg) expired due to systemic
      emboli 30 days after left ventricular assist device support. In summary, these
      results suggest that the Medos ventricular assist device cannula and a
      centrifugal pump is an option for temporary left ventricular assist device
      support in patients with intractable heart failure and as a bridge to heart
      transplantation.

PMID- 20050296
TI  - The PediPump: a versatile, implantable pediatric ventricular assist device-
      update IV.
AB  - Cleveland Clinic's PediPump (Cleveland, OH, USA) is a ventricular assist device
      designed for the support of pediatric patients. The PediPump is a mixed-flow
      ventricular assist device with a magnetically suspended impeller measuring 10.5
      mm in diameter by 64.5 mm in length. Progress and achievements for the PediPump
      program are considered according to the development project's three primary
      objectives: Basic engineering: along with size reductions, substantial design
      improvements have been incorporated in each design iteration including the motor,
      magnetic bearings, axial touch points, and heat transfer path; Anatomic modeling
      and device fitting studies: Techniques based on computed tomography and magnetic
      resonance imaging have been developed to create three-dimensional anatomic
      modeling and device-fitting tools to facilitate device implantation and to assist
      in preoperative planning. For in vivo testing, to date, six acute (6-h duration)
      and nine chronic (30-day target duration) implantations have been performed in
      sheep; the implantation of the PediPump appears to be relatively easy with
      excellent hemodynamic performance and minimal hemolysis during support. Cleveland
      Clinic's PediPump program supported by the National Heart, Lung and Blood
      Institute's Pediatric Circulatory Support Program has led to the development of a
      pediatric ventricular assist device that has satisfactory performance in
      preclinical evaluation and appears to be ready to support a program of clinical
      testing.

PMID- 20050297
TI  - Reply: Fertility preservation in   adolescent males: experience   over 22 years
      at Rouen   University Hospital.

PMID- 20050298
TI  - Acute caffeine ingestion: clinical features in patients attending the emergency
      department and Scottish poison centre enquiries between 2000 and 2008.
AB  - BACKGROUND AND AIMS: Little information is available regarding the healthcare
      burden associated with deliberate caffeine ingestion. The present study sought to
      establish the impact of caffeine ingestion on hospital attendances and Poisons
      Centre enquiries in Scotland. METHODS: Retrospective analyses of clinical data
      from patients attending the Royal Infirmary of Edinburgh after acute caffeine
      ingestion, and TOXBASE enquiries from Scotland regarding caffeine poisoning
      between 2000-2008 inclusive. Cochran-Armitage trend tests were used to evaluate
      changes in annual admissions and TOXBASE enquiries. RESULTS: There were 43
      hospital attendances due to deliberate caffeine ingestion, representing 0.2% of
      all poisoning cases. The median (interquartile range) stated dose was 1040 mg
      (600-1500 mg). Minor gastrointestinal symptoms were common, and no patient
      developed features of severe toxicity. There were 1418 enquiries to TOXBASE
      concerning caffeine poisoning, representing 0.2% of all poisoning enquiries from
      Scotland. The proportions of hospital admissions and TOXBASE enquiries due to
      caffeine ingestion have remained constant. CONCLUSION: Caffeine ingestion is
      uncommon, and results in only a small number of hospital attendances and Poisons
      Centre enquiries. In contrast to patterns reported elsewhere, the prevalence of
      caffeine abuse has not increased in Scotland over recent years.

PMID- 20050299
TI  - Reply: A new method for testing   a hypothesis on a cause of   polycystic ovary
      syndrome.

PMID- 20050300
TI  - Effects of electroacupuncture treatment on impaired cognition and quality of life
      in Taiwanese stroke patients.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of
      electroacupuncture on cognitive function and health-related quality of life in
      patients who have had a stroke. DESIGN: This clinical trial employed a
      prospective, randomized, single-blind design. SETTINGS/LOCATION: The study was
      conducted at the department of rehabilitation medicine, Tri-Service General
      Hospital, Taipei, Taiwan. SUBJECTS: Thirty-eight (38) participants were
      recruited, but only 33 completed the study. Seventeen (17) stroke participants
      with cognitive impairment were assigned to the treatment group and 16 were
      assigned to the control group. INTERVENTIONS: Electroacupuncture was applied to
      acupuncture points PC6 and HT7 for 20 minutes twice a week for 8 weeks in the
      treatment group, while participants in each group continued rehabilitation.
      OUTCOME MEASURES: Cognitive assessment (LOTCA-G) and quality-of-life assessment
      (SF-36 and SS-QOL) were carried out in each group at baseline and at 8 weeks
      after treatment. RESULTS: Significant improvement was detected in four subtests
      of LOTCA-G: orientation, perception, praxis, and attention ( p<0.05) between
      treatment and control groups. Significant improvement was also indicated in
      subscales of SF-36 (RP, VT, SF, RE, MH, MCS) and SS-QOL (language) ( p<0.05). No
      correlation was noted between the variables of LOTCA-G and SF-36/SS-QOL except
      four matches: Memory (LOTCA-G) and Mental Component Summary (SF-36): r=0.492;
      Memory (LOTCA-G) and Personality (SS-QOL): r=0.485; Praxis (LOTCA-G) and Language
      (SS-QOL): r=0.616; Orientation (LOTCA-G), and Language (SS-QOL): r=0.534.
      CONCLUSIONS: The results of this study confirm a positive effect of
      electroacupuncture on cognition and quality of life in patients who had a stroke.
      Future research will be required to evaluate potential mechanisms and potential
      long-term benefits.

PMID- 20050301
TI  - Ecological, morphological and genetic divergence of sympatric North Atlantic
      killer whale populations.
AB  - Ecological divergence has a central role in speciation and is therefore an
      important source of biodiversity. Studying the micro-evolutionary processes of
      ecological diversification at its early stages provides an opportunity for
      investigating the causative mechanisms and ecological conditions promoting
      divergence. Here we use morphological traits, nitrogen stable isotope ratios and
      tooth wear to characterize two disparate types of North Atlantic killer whale. We
      find a highly specialist type, which reaches up to 8.5 m in length and a
      generalist type which reaches up to 6.6 m in length. There is a single fixed
      genetic difference in the mtDNA control region between these types, indicating
      integrity of groupings and a shallow divergence. Phylogenetic analysis indicates
      this divergence is independent of similar ecological divergences in the Pacific
      and Antarctic. Niche-width in the generalist type is more strongly influenced by
      between-individual variation rather than within-individual variation in the
      composition of the diet. This first step to divergent specialization on different
      ecological resources provides a rare example of the ecological conditions at the
      early stages of adaptive radiation.

PMID- 20050302
TI  - From the editors.

PMID- 20050303
TI  - Signalling: ABA's greatest hits.

PMID- 20050304
TI  - Sumoylation: Wrestling with filaments.

PMID- 20050305
TI  - To adhere or not to adhere?

PMID- 20050306
TI  - Development: Tension at the borders.

PMID- 20050307
TI  - DNA replication: Keeping up with the leader.

PMID- 20050308
TI  - Small RNAs: Sorting the strands.

PMID- 20050309
TI  - Endocytosis: WASHed and sorted.

PMID- 20050310
TI  - Protein degradation: Step by step.

PMID- 20050311
TI  - Two conformations are better than one: domain motion in cytochrome P450
      reductase. conformational equilibria revealed by nmr and small-angle X-ray
      scattering.

PMID- 20050312
TI  - Low lymphocyte count in acute phase of ST-segment  elevation myocardial
      infarction predicts long-term recurrent  myocardial infarction.
AB  - OBJECTIVE: We sought to determine the relationship between the lowest lymphocyte
      count (lymphocyte(min))obtained within the first 96 h of symptoms onset and the
      risk of postdischarge recurrent spontaneous myocardial infarction (re-MI) in
      patients admitted with ST-segment elevation MI (STEMI). METHODS: We analyzed 549
      consecutive patients admitted with STEMI from a single academic hospital.
      Lymphocyte counts were determined at admission and routinely during the first 96
      h. Lymphocyte(min) was selected as the main exposure. Patients with inflammatory
      or infectious diseases, in-hospital death, or reinfarction were excluded from the
      analysis (final sample= 426 patients). Lymphocyte(min) was divided into quartiles
      (Q) and their association with re-MI was assessed by competing risk analysis.
      Postdischarge death and coronary revascularization were considered competing
      events. RESULTS: During a median follow-up of 36 months, 53 re-MI (12.4%) were
      registered. The re-MI crude rate was significantly higher in patients in the
      lowest lymphocyte(min) quartile (Q1r1045 cells/ml) compared with Q2-Q4: 22.4,
      9.4, 8.4, 9.4%, respectively; P =0.005. In a multivariate setting, Q1 was also
      associated with a significant increased risk of re-MI compared with Q2-Q4 (hazard
      ratio: 2.04, 95% confidence interval: 1.11-3.76; P = 0.021). CONCLUSION: Low
      lymphocyte count obtained within the first 96 h of a STEMI predicts the risk of
      re-MI.

PMID- 20050313
TI  - [Moses Maimonides, "physician of princes, prince of physicians].

PMID- 20050314
TI  - Sensitive cardiac troponin assays.

PMID- 20050315
TI  - Sudden infant death syndrome.

PMID- 20050316
TI  - Proceedings of the 2nd Annual Conference of the International Society for the
      Study of Drug Policy. March 2008. Lisbon, Portugal.

PMID- 20050317
TI  - China Tregs 2008. Proceedings of the International Conference on Regulatory T
      Cells and Clinical Application in Human Diseases. Beijing, China. on 25-27
      October 25-27, 2008.

PMID- 20050318
TI  - From arts to science. Proceedings of the 4th International Symposium on
      Sourdough. October 14-17, 2009. Freising, Germany.

PMID- 20050319
TI  - Changing the "channel": aminopyridines potentiate synaptic and neuromuscular
      transmission by targeting the voltage-activated calcium channel beta subunit.

PMID- 20050320
TI  - Sensitive cardiac troponin assays.

PMID- 20050321
TI  - Injectable collagenase clostridium histolyticum for Dupuytren's contracture.

PMID- 20050322
TI  - Sudden infant death syndrome.

PMID- 20050323
TI  - Electronic patient records.

PMID- 20050324
TI  - Certified implant specialists not playing "what's my line".

PMID- 20050325
TI  - Question: what is the definition of a "specialist"? Answer: no one knows! (at
      least not in Florida...and at least not for now).

PMID- 20050326
TI  - [Clinical and epidemiologic peculiarities of metabolic syndrome in patients with
      occupational diseases].
AB  - The article covers results of metabolic syndrome epidemiology studies in patients
      with occupational diseases. The authors compared occurrence of metabolic syndrome
      for various diagnostic criteria, analyzed prevalence of metabolic syndrome in
      individuals with various length of service in hazardous conditions, defined main
      clinical types of the metabolic syndrome manifestation in patients with
      occupational diseases.

PMID- 20050327
TI  - The first composite face and maxilla transplant.

PMID- 20050328
TI  - Uganda registers successes with child-health volunteers.

PMID- 20050329
TI  - Cooperative action of CD8 T lymphocytes and natural killer cells  controls tumour
      growth under conditions of restricted T-cell  receptor diversity.
AB  - In mice expressing a transgenic T-cell receptor (TCR; TCRP1A) of DBA/2 origin
      with reactivity towards a cancer-germline antigen P1A, the number of TCRP1A CD8+
      T cells in lymphoid organs is lower in DBA/2 than in B10.D2 or B10.D2(x DBA/2)F1
      mice. This reduction results from haemopoietic cell autonomous differences in the
      differentiation of the major histocompatibility complex class I-restricted TCRP1A
      thymocytes controlled by DBA/2 versus B10.D2-encoded genes. We report here that
      the lower number of TCRP1A CD8+ T cells in DBA/2 mice correlated with their poor
      resistance to P1A-expressing mastocytoma solid tumours. Functional potency of
      CD8+ cytolytic T lymphocytes (CTL) from the above strains was not compromised,
      but their number after expansion appeared to be influenced by their genetic
      background. Intriguingly, non-transgenic DBA/ 2 mice resisted P1A+ tumours more
      efficiently despite poor representation of P1A-specific CTL. This was partly the
      result of their more heterogeneous TCR repertoire, including reactivity to non
      P1A tumour antigens because mice that had rejected a P1A+ tumour became resistant
      to a P1A) variant of the tumour. Such 'cross-resistance' did not develop in the
      TCRP1A transgenic mice. Nonetheless, reconstitution of RAGo/o mice with TCRP1A
      CD8+ T cells, with or without CD4+ T cells, or exclusive representation of TCRP1A
      CD8+ T cells in RAGo/o TCRP1A transgenic mice efficiently resisted the growth of
      P1A-expressing tumours. Natural killer cells present at a higher number in RAGo/o
      mice also contributed to tumour resistance, in part through an NKG2D-dependent
      mechanism. Hence, in the absence of a polyclonal T-cell repertoire, precursor
      frequencies of natural killer cells and tumour-specific CTL affect tumour
      resistance.

PMID- 20050330
TI  - Identification of leucocyte surface protein interactions by  high-throughput
      screening with multivalent reagents.
AB  - We describe a high-throughput screening system to detect interactions between
      leucocyte surface proteins, taking into account that these interactions are
      usually of very low affinity. The method involves producing the extracellular
      regions of leucocyte proteins with tags so that they can be bound to
      nanoparticles to provide an avid reagent to screen over an array of 36 similar
      proteins immobilized using the Proteon XPR36 with detection by surface plasmon
      resonance. The system was tested using established interactions that could be
      detected without spurious binding. The ability to detect new interactions was
      shown by identifying a new interaction between carcinoembryonic antigen-related
      cell adhesion molecule 1 and carcinoembryonic antigen-related cell adhesion
      molecule 8.

PMID- 20050331
TI  - Inhibition of cyclooxygenase-2 impairs the expression of essential  plasma cell
      transcription factors and human B-lymphocyte  differentiation.
AB  - Cyclooxygenase (Cox) inhibitors are among the most widely used and commonly
      prescribed medications. Relatively little is understood about their influence on
      human immune responses. Herein, we discovered a novel and important mechanism
      whereby non-steroidal anti-inflammatory drugs (NSAIDs) blunt human B-cell
      antibody production. We demonstrate that the Cox-2 selective small molecule
      inhibitors SC-58125 and NS-398 attenuate the production of human antibody
      isotypes including immunoglobulin M (IgM), IgG1, IgG2, IgG3 and IgG4. In
      addition, inhibition of Cox-2 significantly reduced the generation of CD38+ IgM+
      and CD38+ IgG+ antibody-secreting cells. Interestingly, we discovered that
      inhibition of Cox-2 activity in normal human B cells severely reduced the
      messenger RNA and protein levels of the essential plasma cell transcription
      factor, Blimp-1. These observations were mirrored in Cox-2-deficient mice, which
      had reduced CD138+ plasma cells and a near loss of Blimp-1 expression. These new
      findings demonstrate a critical role for Cox-2 in the terminal differentiation of
      human B lymphocytes to antibody-secreting plasma cells. The use of NSAIDs may
      adversely influence the efficacy of vaccines, especially in the
      immunocompromised, elderly and when vaccines are weakly immunogenic.

PMID- 20050332
TI  - Tumor necrosis factor-a augments lipopolysaccharide-induced  suppressor of
      cytokine signalling 3 (SOCS-3) protein expression  by preventing the degradation.
AB  - The regulatory role of tumour necrosis factor-a (TNF-a) on the expression of
      suppressor of cytokine signalling 3 (SOCS-3) in response to lipopolysaccharide
      (LPS) was examined using peritoneal macrophages from TNF-a-deficient mice. The
      LPS-induced SOCS-3 expression was markedly augmented in macrophages from wild
      type mice whereas such augmentation was not seen in the cells from TNF-a
      deficient mice. However, there was no significant difference in the level of SOCS
      3 messenger RNA expression between macrophages from wild-type mice and those from
      TNF-a-deficient mice. The addition of exogenous TNF-a augmented the LPS-induced
      SOCS-3 expression in macrophages from TNF-a-deficient mice. The pulse chase
      analysis suggested augmented degradation of LPS-induced SOCS-3 protein in
      macrophages from TNF-a-deficient mice. Moreover, MG 132, a 26S proteasome
      inhibitor, sustained the LPS-induced SOCS-3 expression in those cells. The
      tyrosine phosphorylation of SOCS-3 was definitely induced in LPS-stimulated
      macrophages from TNF-a-deficient mice but not wild-type mice. A tyrosine
      phosphatase inhibitor enhanced the tyrosine phosphorylation of SOCS-3 in wild
      type mice and accelerated the degradation. Therefore, it was suggested that TNF-a
      prevented the degradation of SOCS-3 protein via inhibition of the tyrosine
      phosphorylation in LPS-stimulated macrophages.

PMID- 20050333
TI  - The function of CCR3 on mouse bone marrow-derived mast cells  in vitro.
AB  - The mechanisms governing the population of tissues by mast cells are not fully
      understood, but several studies using human mast cells have suggested that
      expression of the chemokine receptor CCR3 and migration to its ligands may be
      important. In CCR3-deficient mice, a change in mast cell tissue distribution in
      the airways following allergen challenge was reported compared with wild-type
      mice. In addition, there is evidence that CCR3 is important in mast cell
      maturation in mouse. In this study, bone marrow-derived mast cells (BMMCs) were
      cultured and CCR3 expression and the migratory response to CCR3 ligands were
      characterized. In addition, BMMCs were cultured from wild-type and CCR3-deficient
      mice and their phenotype and migratory responses were compared. CCR3 messenger
      RNA was detectable in BMMCs, but this was not significantly increased after
      activation by immunoglobulin E (IgE). CCR3 protein was not detected on BMMCs
      during maturation and expression could not be enhanced after IgE activation.
      Resting and IgE-activated immature and mature BMMCs did not migrate in response
      to the CCR3 ligands eotaxin- 1 and eotaxin-2. Comparing wild-type and CCR3
      deficient BMMCs, there were no differences in mast cell phenotype or ability to
      migrate to the mast cell chemoattractants leukotriene B4 and stem cell factor.
      The results of this study show that CCR3 may not mediate mast cell migration in
      mouse BMMCs in vitro. These observations need to be considered in relation to the
      findings of CCR3 deficiency on mast cells in vivo.

PMID- 20050334
TI  - The importance of understanding basic biology.

PMID- 20050335
TI  - Systemic inflammation as a confounding factor in cancer biomarker discovery and
      validation.

PMID- 20050336
TI  - Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin
      resistant Staphylococcus aureus pneumonia.
AB  - OBJECTIVE: To investigate whether adding rifampicin to vancomycin could cure more
      patients with nosocomial methicillin-resistant Staphylococcus aureus pneumonia
      compared with vancomycin-only. DESIGN: Prospective randomized open-label study.
      SETTING: Medical intensive care unit in Seoul, Korea. PATIENTS: Ninety-three of
      183 patients with Gram-positive nosocomial pneumonia. INTERVENTIONS: The enrolled
      patients with subsequently documented methicillin-resistant Staphylococcus aureus
      pneumonia (modified intention-to-treat population) were treated with vancomycin
      (1 g intravenous every 12 hrs) plus rifampicin (300 mg twice daily by mouth) (n =
      41) or with vancomycin-only (n = 42). The intended treatment (at least 5 days)
      was completed in 30 patients in the vancomycin plus rifampicin group and 34
      patients in the vancomycin-only group (per protocol population). MEASUREMENTS AND
      MAIN RESULTS: The primary outcome was the clinical cure rate on day 14 of
      treatment. The secondary outcomes were intensive care unit mortality on days 28
      and 60, and microbiological eradication on day 14. The clinical cure rate in the
      modified intention-to-treat population was 53.7% (22 of 41) in the vancomycin
      plus rifampicin group, and 31.0% (13 of 42) in the vancomycin-only group (p =
      .047), and the respective rates in the per protocol population were 63.3% (19 of
      30) and 38.2% (13 of 34) (p = .079). The respective mortality rates were nine
      (22.0%) of 41 and 16 (38.1%) of 42 on day 28 (p = .151), and 11 (26.8%) of 41 and
      21 (50.0%) of 42 on day 60 (p = .042). The microbiological eradication rate did
      not differ between groups (p = .472). CONCLUSIONS: Vancomycin plus rifampicin
      seems to be more effective than vancomycin alone in the treatment of nosocomial
      methicillin-resistant Staphylococcus aureus pneumonia.

PMID- 20050337
TI  - Chad A. Ellis, Ph.D., appointed Deputy Director for Research at Yale Cancer
      Center.

PMID- 20050338
TI  - Michele Carbone appointed as Director of University of Hawaii's Cancer Research
      Center.

PMID- 20050339
TI  - Federal stimulus package funds innovative cancer studies.

PMID- 20050340
TI  - Using RNAi-based  technique, CSHL  scientists find new tumor suppressor genes in 
      lymphoma.

PMID- 20050341
TI  - NIH awards M.D. Anderson 84 research grants from stimulus funds.

PMID- 20050342
TI  - Inhibitor of heat shock protein is a potential anticancer drug, Penn study finds.

PMID- 20050343
TI  - [Early failure of the Birmingham hip resurfacing].

PMID- 20050344
TI  - [Suspension-plasty or simple resection?].

PMID- 20050345
TI  - [Antibiotic prophylaxis--what works the best?].

PMID- 20050346
TI  - [Hip para-articular femoral fracture--operate immediately?].

PMID- 20050347
TI  - [Management of advanced epithelial cancer of the ovary: towards a change in
      practice?].

PMID- 20050348
TI  - [A foreign body in the neck with injured larynx and common carotid artery].

PMID- 20050349
TI  - [A case of follicular cyst in the maxillary sinus].

PMID- 20050350
TI  - [About the Valsalva maneuver].

PMID- 20050351
TI  - Characteristics of physical measurement consent in a population-based survey of
      older adults.
AB  - BACKGROUND: Collecting physical measurements in population-based health surveys
      has increased in recent years, yet little is known about the characteristics of
      those who consent to these measurements. OBJECTIVE: To examine the
      characteristics of persons who consent to physical measurements across several
      domains, including one's demographic background, health status, resistance
      behavior toward the survey interview, and interviewer characteristics. RESEARCH
      DESIGN, SUBJECTS, AND MEASURES: We conducted a secondary data analysis of the
      2006 Health and Retirement Study, a nationally-representative panel survey of
      older adults aged 51 and older. We performed multilevel logistic regressions on a
      sample of 7457 respondents who were eligible for physical measurements. The
      primary outcome measure was consent to all physical measurements. RESULTS:
      Seventy-nine percent (unweighted) of eligible respondents consented to all
      physical measurements. In weighted multilevel logistic regressions controlling
      for respondent demographics, current health status, survey resistance indicators,
      and interviewer characteristics, the propensity to consent was significantly
      greater among Hispanic respondents matched with bilingual Hispanic interviewers,
      patients with diabetes, and those who visited a doctor in the past 2 years. The
      propensity to consent was significantly lower among younger respondents, those
      who have several Nagi functional limitations and infrequently participate in
      "mildly vigorous" activities, and those interviewed by black interviewers. Survey
      resistance indicators, such as number of contact attempts and interviewer
      observations of resistant behavior in prior wave iterations of the Health and
      Retirement Study were also negatively associated with physical measurement
      consent. The propensity to consent was unrelated to prior medical diagnoses,
      including high blood pressure, cancer (excluding skin), lung disease, heart
      abnormalities, stroke, and arthritis, and matching of interviewer and respondent
      on race and gender. CONCLUSIONS: Physical measurement consent is not strongly
      associated with one's health status, though the findings are somewhat mixed. We
      recommend that physical measurement results be adjusted for characteristics
      associated with the likelihood of consent, particularly functional limitations,
      to reduce potential bias. Otherwise, health researchers should exercise caution
      when generalizing physical measurement results to the population at large,
      including persons with functional limitations that may affect their
      participation.

PMID- 20050352
TI  - Incremental value of using Medicaid claim files to study comorbid conditions and
      treatments in dually eligible beneficiaries.
AB  - BACKGROUND: Although investigations using Medicare claims files are ubiquitous in
      the health services research literature, Medicaid claims files are used less
      frequently. Nonetheless, Medicaid is the major payer for healthcare among low
      income persons. OBJECTIVE: To assess the added value of Medicaid claim files for
      identifying comorbid conditions and cancer treatments in a dually eligible
      sample. RESEARCH DESIGN: Data were obtained from linked statewide tumor
      registries from 2 contiguous Midwestern states (Michigan and Ohio), Medicare and
      Medicaid enrollment files, and Medicare and Medicaid claims files. We estimated
      the prevalence of Charlson Comorbidity Index conditions by counting the number of
      patients with these conditions in the Medicare claims files alone. We then
      estimate the expected percent increase in the prevalence of comorbid conditions
      (along with the 95% confidence interval) that could be obtained by using both
      Medicare and Medicaid claim files. We followed a similar procedure to identify
      treatments provided to dually eligible patients. RESULTS: Medicaid claims added
      very few individuals with comorbid conditions over those identified through
      Medicare claim files. The increase in the prevalence of comorbid conditions was
      between 0% and 2.5%. Likewise, Medicaid claims identified few individuals with
      cancer treatments who were not already identified through Medicare claim files,
      although variations were noted between the 2 states. CONCLUSIONS: This study
      suggests that the incremental value of Medicaid inpatient, outpatient, and
      carrier claims is relatively small over what can be obtained from Medicare claims
      data.

PMID- 20050354
TI  - [Myths and realities: the case of aspirin].

PMID- 20050353
TI  - Rethinking trial strategies for stroke and patent  foramen ovale.
AB  - PURPOSE OF REVIEW: The cause of stroke remains unknown in roughly one third of
      patients, despite extensive investigation. The prevalence of patent foramena
      ovale (PFOs) in the general population is around 25%, but it is doubled in
      cryptogenic stroke patients. This suggests a causal relationship between PFO and
      cryptogenic stroke. This has generally been attributed to paradoxical embolism.
      Regardless of mechanism, nearly 30,000 young patients each year have a
      cryptogenic stroke and PFO. Optimal management is uncertain. RECENT FINDINGS:
      Many physicians recommend PFO closure, an intuitively attractive mechanical
      solution for stroke prevention. Unfortunately, the benefit of PFO closure in
      patients with stroke has not been demonstrated. There are ongoing clinical trials
      comparing the safety and efficacy of PFO closure with that of medical therapy.
      Interpreting these trials will be complicated by two issues: first, it is unclear
      whether a patient's PFO is causally related to the event ('pathogenic') or not
      ('incidental'); and second, recurrent strokes may be due to paradoxical embolism
      or another stroke mechanism. SUMMARY: Substantial heterogeneity of patients
      within trials along these two dimensions of risk may make overall trial results
      difficult to interpret. With appropriate analyses, the trials may be more
      informative than the overall data may suggest.

PMID- 20050355
TI  - FL: pre-suit notice of expert witness required: patient's sister--a veteran nurse
      not qualified: Derespina, v. North Broward Hospital Dist., 4D08-2670 (10/14/2009)
      FL.

PMID- 20050356
TI  - What happened to my State Medical Society?

PMID- 20050357
TI  - Salad days.

PMID- 20050358
TI  - A possible solution, but not the last word.

PMID- 20050359
TI  - The point of control: Can a regulated organ market be moral?

PMID- 20050360
TI  - Improvisation.

PMID- 20050361
TI  - Irrational basis: the legal status of medical marijuana.

PMID- 20050362
TI  - After insurance reform: an adequate safety net can bring us to universal
      coverage.

PMID- 20050363
TI  - The nesting-egg problem: why comparative effectiveness research is trickier than
      it looks.

PMID- 20050364
TI  - The quality mantra: proceed carefully.

PMID- 20050365
TI  - A tool to strengthen the doctor-patient relationship.

PMID- 20050366
TI  - Define "effective" the curious case of chronic cancer.

PMID- 20050367
TI  - Lessons from abroad.

PMID- 20050368
TI  - Charting the future. Credentialing, privileging, quality, and evaluation in
      clinical ethics consultation.
AB  - Clinical ethics consultation has become an important resource, but unlike other
      health care disciplines, it has no accreditation or accepted curriculum for
      training programs, no standards for practice, and no way to measure
      effectiveness. The Clinical Ethics Credentialing Project was launched to pilot
      test approaches to train, credential, privilege, and evaluate consultants.

PMID- 20050370
TI  - Health reform: what's prevention got to do with it?

PMID- 20050371
TI  - Editorial. Recent research in a variety of areas of drug metabolism.

PMID- 20050369
TI  - Risk and the pregnant body.
AB  - Reasoning well about risk is most challenging when a woman is pregnant, for
      patient and doctor alike. During pregnancy, we tend to note the risks of medical
      interventions without adequately noting those of failing to intervene, yet when
      it's time to give birth, interventions are seldom questioned, even when they
      don't work. Meanwhile, outside the clinic, advice given to pregnant women on how
      to stay healthy in everyday life can seem capricious and overly cautious. This
      kind of reasoning reflects fear, not evidence.

PMID- 20050372
TI  - Prediction of deleterious functional effects of non-synonymous single nucleotide
      polymorphisms in human nuclear receptor genes using a bioinformatics approach.
AB  - The nuclear receptor (NR) superfamily represents an important group of regulating
      factors that control the expression of a number of target genes including those
      encoding important drug metabolizing enzymes and drug transporters. Single
      nucleotide polymorphism (SNP) is the most common mutation in the human genome and
      a large number of SNPs have been identified to date. It is unlikely to examine
      the functional impact of all these mutations using an experimental approach. As
      such, we employed two algorithms, Sorting Intolerant from Tolerant (SIFT) and
      Polymorphism Phenotyping (PolyPhen) to predict the impact of non-synonymous SNPs
      (nsSNPs) on NR activities and disease susceptibility. We identified 442 nsSNPs in
      a systematic screening of 48 human NR genes. Using SIFT, of 442 amino acid
      substitutions, 289 (65.38%) were classified as "intolerant". The PolyPhen program
      classified 269 (60.86%) of them as "probably damaging" or "possibly damaging".
      The results from the two algorithms were in concordance. Among the 442 mutations,
      229 of them have been functionally characterized. SIFT predicted 192 of these
      nsSNPs as "intolerant", resulting in a correct prediction rate of 83.84%, while
      PolyPhen gave a prediction rate of 76.86%. For 216 nsSNPs of the androgen
      receptor gene, 149 nsSNPs have been functionally studied and most (121) of them
      resulted in a reduction of receptor activity. SIFT sorted 187 out of 216 as
      "intolerant" (86.57%) and PolyPhen identified 159 out of 216 as "potentially
      intolerant" (73.61%). These results indicate that both SIFT and PolyPhen are
      useful and efficient tools to predict the functional effects of nsSNPs of human
      NR genes.

PMID- 20050373
TI  - Molecular mechanisms of melatonin anticancer effects.
AB  - The authors have shown that, via activation of its MT1 receptor, melatonin
      modulates the transcriptional activity of various nuclear receptors and the
      proliferation of both ER alpha+ and ER alpha- human breast cancer cells.
      Employing dominant-negative (DN) and dominant-positive (DP) G proteins, it was
      demonstrated that G alpha i2 proteins mediate the suppression of estrogen-induced
      ER alpha transcriptional activity by melatonin, whereas the G alpha q proteins
      mediate the enhancement of retinoid-induced RAR alpha transcriptional activity by
      melatonin. In primary human breast tumors, the authors' studies demonstrate an
      inverse correlation between ER alpha and MT1 receptor expression, and confocal
      microscopic studies demonstrate that the MT1 receptor is localized to the caveoli
      and that its expression can be repressed by estrogen and melatonin. Melatonin,
      via activation of its MT1 receptor, suppresses the development and growth of
      breast cancer by regulation of growth factors, regulation of gene expression,
      regulation of clock genes, inhibition of tumor cell invasion and metastasis, and
      even regulation of mammary gland development. The authors have previously
      reported that the clock gene, Period 2 (Per2), is not expressed in human breast
      cancer cells but that its reexpression in breast cancer cells results in
      increased expression of p53 and induction of apoptosis. The authors demonstrate
      that melatonin, via repression of ROR alpha transcriptional activity, blocks the
      expression of the clock gene BMAL1. Melatonin's blockade of BMAL1 expression is
      associated with the decreased expression of SIRT1, a member of the Silencing
      Information Regulator family and a histone and protein deacetylase that inhibits
      the expression of DNA repair enzymes (p53, BRCA1 & 2, and Ku70) and the
      expression of apoptosis-associated genes. Finally, the authors developed an MMTV
      MT1-flag mammary knock-in transgenic mouse that displays reduced ductal
      branching, ductal epithelium proliferation, and reduced terminal end bud
      formation during puberty and pregnancy. Lactating female MT1 transgenic mice show
      a dramatic reduction in the expression of beta-casein and whey acidic milk
      proteins. Further analyses showed significantly reduced ER alpha expression in
      mammary glands of MT1 transgenic mice. These results demonstrate that the MT1
      receptor is a major transducer of melatonin's actions in the breast, suppressing
      mammary gland development and mediating the anticancer actions of melatonin
      through multiple pathways.

PMID- 20050374
TI  - Circadian disruption, fatigue, and anorexia clustering in advanced cancer
      patients: implications for innovative therapeutic approaches.
AB  - A disruption of the circadian timing system, as identified by monitoring of
      marker biorhythms, is common in cancer patients. The recording of the rest
      activity rhythm with a wrist actigraph has been commonly used. This noninvasive
      monitoring allows a robust estimation of circadian disruption. The authors have
      previously found that altered patterns of circadian rest-activity rhythms are
      significantly and independently associated with the severity of fatigue and
      anorexia in patients with metastatic colorectal cancer. Elevated proinflammatory
      cytokines could partly account for this circadian disruption and its associated
      constitutional symptoms. Here, the authors present and discuss the data
      supporting the hypothesis that circadian disruption is often associated with
      fatigue and anorexia, which in turn further alter and dampen circadian
      synchronization, thus, creating a vicious cycle. This body of evidence paves the
      path for innovative therapeutic approaches targeting the circadian timing system
      in an effort to diminish constitutional symptoms induced by cancer and some
      anticancer treatments.

PMID- 20050375
TI  - Prevalence of upper cervical vertebrae anomalies in patients with cleft lip
      and/or palate and noncleft patients.

PMID- 20050376
TI  - Comparison of dental caries prevalence in patients with cleft lip and/or palate
      and their sibling controls.
AB  - OBJECTIVE: To evaluate the prevalence of dental caries in patients with cleft lip
      and/or palate and their cleft-free sibling controls. METHODS: The two subject
      groups (patient and control) comprised 106 participants. The former group
      consisted of 53 patients with cleft lip and/or palate,aged 12 to 29 years, who
      visited the Oral and Maxillofacial Surgery Hospital at Damascus University of
      Syria. The control group consisted of the patients' siblings who had no
      clefts,and they were sex matched to the patient group. Dental caries were
      examined clinically and were reported using the decayed,missing, and filled
      permanent teeth (DMFT) index. The DMFT scores were compared between the two
      groups. RESULTS: The author found an overall association of dental caries with
      the presence of cleft lip and/or palate (odds ratio = 2.52; 95% confidence
      interval =1.389-4.574; p , .05). The DMFT index scores were proportionally higher
      inpatients with cleft lip and/or palate compared with the control group (p ,
      .001). CONCLUSION: Subjects with cleft lip and palate are susceptible to dental
      caries independently of socioeconomic status.

PMID- 20050377
TI  - Interactive Medical Case. Painful purple toes.

PMID- 20050378
TI  - Which prostheses are cost-effective?

PMID- 20050382
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20050383
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20050384
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20050385
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20050386
TI  - Dabigatran versus warfarin in patients with atrial fibrillation.

PMID- 20050387
TI  - Sex hormone-binding globulin and risk of type 2 diabetes.

PMID- 20050388
TI  - Sex hormone-binding globulin and risk of type 2 diabetes.

PMID- 20050389
TI  - Maternal and neonatal herpes simplex virus infections.

PMID- 20050390
TI  - Clinical trials in ventilator treatment: current perspectives and  future
      challenges.
AB  - PURPOSE OF REVIEW: Mortality/morbidity-based end points have been useful in
      evaluating treatments that modulate 'mediator variables' with a large effect
      size. Ventilation is usually a supportive measure, and hence is best seen as a
      'moderator variable'. It can, therefore, have only a modest impact on disease
      specific mortality. In this context, over reliance on final outcome-based end
      points (mortality, length of stay, etc.) risks the abandonment of several
      potentially useful developments. These concepts are important in considering how
      future developments should be evaluated. MAIN FINDINGS: A modest effect size
      implies that large sample sizes will be necessary to demonstrate
      mortality/morbidity benefits. Recruiting large numbers over
      geographically/culturally/economically heterogeneous areas over long periods
      (during which clinical practice is unlikely to remain constant) has several
      limitations. Furthermore, manifestations of critical illness are based on
      nonlinear interactions between insult, host responses and other moderator
      variables. In such nonlinear systems the final outcome is unpredictable and does
      not follow simple linear assumptions. Such 'unexpected' events occurring in
      clinical trials involving moderator variables, may potentially lead to erroneous
      conclusions. SUMMARY: It is crucial that a more dynamic approach, not based on
      final outcome alone, is considered in designing new clinical trials involving new
      ventilation strategies.

PMID- 20050391
TI  - Cost-effectiveness of routine rapid human immunodeficiency virus antibody testing
      before DNA-PCR testing for early diagnosis of infants in resource-limited
      settings.
AB  - BACKGROUND: Infants born to HIV-infected women should receive HIV testing to
      allow early diagnosis and treatment. Recommendations for resource-limited
      settings stress laboratory-based virologic assays. While effective, these tests
      are logistically complex and expensive. This study explored the cost
      effectiveness of incorporating initial screening with rapid HIV tests (RHT) into
      the conventional testing algorithm to screen-out HIV-uninfected infants, thereby
      reducing the need for costly virologic testing. METHODS: Data on HIV prevalence,
      RHT sensitivity and specificity, and costs were collected from 820 HIV-exposed
      children (1.5-18 months) attending 2 postnatal screening programs in Uganda
      during July 2005 to December 2006. Cost-effectiveness models compared the
      conventional testing algorithm DNA polymerase chain reaction (DNA-PCR with Roche
      Amplicor v1.5) with a modified algorithm (initial RHT to screen-out HIV
      uninfected infants before DNA-PCR). RESULTS: The model estimated that the
      conventional algorithm would identify 94.3% (91.8%-94.7%) of HIV-infected
      infants, compared with 87.8% (79.4%-90.5%) for a modified algorithm using RHT
      (HIV 1/2 Determine) and excluding the need for DNA-PCR for HIV antibody-negative
      infants. Costs per infant were $23.47 ($23.32-$23.76) for the conventional
      algorithm and between $22.75 ($21.89-$23.31) and $7.58 ($6.41-$10.75) for the
      modified algorithm, depending on infant age and symptoms. Compared with the
      conventional algorithm, costs per HIV-infected infant identified using the
      modified algorithm were higher in 1.5-to 3-month-old infants, but significantly
      lower in 3-month-old and older infants. Models replicating the whole infant
      testing program showed the modified algorithm would have marginally lower
      sensitivity, but would reduce total program costs by 27% to 40%, producing an
      incremental cost-effectiveness ratio of $1489 ($686-$6781) for the conventional
      versus modified algorithms. CONCLUSIONS: Screening infants with RHT before DNA
      PCR is cost-effective in infants 3 months old or older. Incorporating RHT into
      early infant testing programs could improve cost-effectiveness and reduce program
      costs.

PMID- 20050392
TI  - iPS cells: potent stuff.

PMID- 20050393
TI  - Primer: induced pluripotency.

PMID- 20050395
TI  - Patent watch: Progress in three key patent disputes in 2009.

PMID- 20050394
TI  - Information from the voice fundamental frequency (F0) region accounts for the
      majority of the benefit when acoustic stimulation is added to electric
      stimulation.
AB  - OBJECTIVES: The aim of this study was to determine the minimum amount of low
      frequency acoustic information that is required to achieve speech perception
      benefit in listeners with a cochlear implant in one ear and low-frequency hearing
      in the other ear. DESIGN: The recognition of monosyllabic words in quiet and
      sentences in noise was evaluated in three listening conditions: electric
      stimulation alone, acoustic stimulation alone, and combined electric and acoustic
      stimulation. The acoustic stimuli presented to the nonimplanted ear were either
      low-pass-filtered at 125, 250, 500, or 750 Hz, or unfiltered (wideband). RESULTS:
      Adding low-frequency acoustic information to electrically stimulated information
      led to a significant improvement in word recognition in quiet and sentence
      recognition in noise. Improvement was observed in the electric and acoustic
      stimulation condition even when the acoustic information was limited to the 125
      Hz-low-passed signal. Further improvement for the sentences in noise was observed
      when the acoustic signal was increased to wideband. CONCLUSIONS: Information from
      the voice fundamental frequency (F0) region accounts for the majority of the
      speech perception benefit when acoustic stimulation is added to electric
      stimulation. We propose that, in quiet, low-frequency acoustic information leads
      to an improved representation of voicing, which in turn leads to a reduction in
      word candidates in the lexicon. In noise, the robust representation of voicing
      allows access to low-frequency acoustic landmarks that mark syllable structure
      and word boundaries. These landmarks can bootstrap word and sentence recognition.

PMID- 20050397
TI  - Workshops to support prison nurses.

PMID- 20050399
TI  - Universal Protocol becomes less prescriptive in its 2010 version.

PMID- 20050400
TI  - [Joint recommendations of AWMF and DGUV in co-operation with DGAUM and DGSMP for
      the development of guidelines and recommendations for the assessment of
      occupational diseases].

PMID- 20050401
TI  - Human rights and genetic technologies.

PMID- 20050402
TI  - Bioethics and human rights: curb your enthusiasm.

PMID- 20050403
TI  - Human rights and American bioethics: resistance is futile.

PMID- 20050404
TI  - Estimated health effects of the 2009 H1N1 pandemic on Tehran and Kerman
      populations.

PMID- 20050405
TI  - A concern about "modeling of H1N1 Flu".

PMID- 20050406
TI  - A medical representative's introduction to Southern Africa, 1938-39.

PMID- 20050407
TI  - A history of health care in South Africa until 1997.

PMID- 20050408
TI  - Dust and fibre levels at Penge amosite mine, 1970-1971.

PMID- 20050409
TI  - The writing life of James D. Watson: writing and publishing "The Double Helix".
AB  - The A.J. Orenstein Memorial Lecture, Medical School, Univ. of the Witwatersrand,
      Johannesburg, 15 August 2007.

PMID- 20050410
TI  - The D'Arbela saga: some African reflections.

PMID- 20050411
TI  - Adventures in the golden age of molecular biology.

PMID- 20050412
TI  - Abstracts of the Annual Cardiovascular Research Technologies Meeting, CTR 2009.
      March 4-6, 2009, Washington, DC, USA.

PMID- 20050413
TI  - Autopsy findings in Witwatersrand gold miners, 1907-1913.
AB  - This article reports autopsy findings in black Witwatersrand gold miners who
      originated mainly from Portuguese East Africa. These men died at the
      Witwatersrand Native Labour Association compound in Johannesburg between 1907 and
      1913, just over 20 years after the discovery of gold in South Africa. At that
      time there were shockingly high levels of death and disease on the mines. The
      main causes of death were pneumonia, meningitis, tuberculosis and dysentery.
      Pneumonia and meningitis were the principle causes of death in new recruits
      arriving from Portuguese East Africa and tuberculosis the main cause of mortality
      in referrals from the mines.

PMID- 20050414
TI  - Identification, genetic and biochemical analysis of genes involved in  synthesis
      of sugar nucleotide precursors of xanthan gum.
AB  - A genetic and biochemical analysis of Xanthomonas campestris chromosomal
      functions required for xanthan polysaccharide synthesis (xps) was undertaken.
      Seven xps DNA regions were isolated after conjugation of chemically induced non
      mucoid mutants with a genomic library of X. campestris DNA. No overlapping
      segments between regions were detected, based on physical mapping, indicating the
      unlinked character of these regions. Clones complementing several different
      mutants belonging to the same region contained overlapping segments of X.
      campestris chromosomal DNA. Complementation and biochemical analysis, and DNA
      mapping were used to identify and characterize xpsZZZ, ZV and VZ DNA regions.
      Mutants in these three regions were able to synthesize both lipid intermediates
      and xanthan gum in vitro when sugar nucleotides were provided as substrates. HPLC
      analysis of the intracellular sugar nucleotide content showed that the XpsIII
      group comprises two different classes of mutants : XpsIIIA, defective in UDP
      glucose, UDP-glucuronic acid and GDP-mannose, and XpsIIIB,defective in GDP
      mannose. XpsIV mutants were defective in UDP-glucose and UDP-glucuronic acid, and
      XpsVI mutants were defective only in UDP-glucuronic acid. Analysis of enzyme
      activities involved in the synthesis of UDP-glucose, GDP-mannose and UDP
      glucuronic acid indicated that the xpsZZZA region affects the activity of the
      phosphoglucomutase/phosphomannomutase enzyme, and the xpsZZZB region affects the
      mannoisomerase/phosphomannoisomerase activities. The xpsZV mutations affect the
      activity of the UDPG-pyrophosphorylase enzyme, and the xps VZ mutations affect
      the activity of the UDPG-dehydrogenase enzyme.

PMID- 20050415
TI  - Changes in lipid composition and arachidonic acid turnover during the life  cycle
      of the yeast Dipodascopsis uninucleata.
AB  - Ungerminated ascospores of Dipodascopsis uninucleata contained 18 times more
      lipid (5.5 % dry wt) than germinated cells; the lipid comprised 58 % (w/w)
      glycolipids, 28 % (w/w) neutral lipids (mainly triacylglycerols)and 14 % (w/w)
      phospholipids (mainly phosphatidylcholine and phosphatidylethanolamine). During
      germination the absolute amounts of all three lipid fractions fell sharply but,
      during the subsequent initiation of hyphal growth,the amount of phospholipids
      increased. As these hyphae began to differentiate for the sexual stage of the
      life cycle,the amount of neutral lipid then increased. The fatty acyl groups of
      the glyco-, neutral and phospholipid fractions throughout the life cycle were
      mainly palmitate (16:0), oleate (18: 1) and linoleate (18:2). The percentage of
      16:O remained constant during the life cycle while the relative amounts of 18:2
      plus alpha-linolenate (18:3) in the glyco-,neutral and phospholipid fractions
      first increased during initiation of growth and then decreased during the onset
      of differentiation. The opposite trend occurred with 18: 1. When
      [(3)H]arachidonic acid (ARA) and [1-(14)C]181: were fed separately to D.
      uninucleata, both were rapidly incorporated into phospholipids. Highest
      incorporation of ARA was in the growth phase; during the onset and remainder of
      the differentiation phase, the amount of ARA decreased in this fraction.
      Incorporation of 18: 1 increased during growth and differentiation, with a
      significant proportion(49% to 57%) being incorporated into triacylglycerols
      compared to a much smaller proportion (12% to 17%) of ARA.

PMID- 20050416
TI  - Positional distribution of fatty acids, and molecular species of polar lipids, 
      in the diatom Phaeodactylum tricornutum.
AB  - Each of the four main polar lipids from Phaeodactylum tricornutum UTEX 640,
      monogalactyosyldiacylglycerol(MGDG), digalactosyldiacylglycerol (DGDG),
      sulphoquinovosyldiacylglycerol (SQDG) and phosphatidylcholine(PC), was separated
      into its molecular species by reverse-phase HPLC, and the positional distribution
      of fatty acids in each species was determined. Numbers of separated peaks in each
      lipid class were: MGDG, 10; DGDG,7; SQDG, 10; and PC, 11. Eicosapentaenoic acid
      (EPA) was present in 20 of the 45 molecular species but predominated in the MGDG
      and DGDG classes, where 13 of the proposed structures contained EPA. EPA was
      always located in the sn-1 position except in two lipid species, MG5 and PC2,
      where it was present at both the sn-1 and sn-2 locations. The predominant polar
      lipid molecular species found in P. tricornutum UTEX 640 were(mg total fatty
      acids per g dry weight of biomass) 20:5-16:4-MG, 41-2; 20:5-16:1-DG, 21.0; 16:1
      16:1-SQ,18-2; and 20:5-16: 1-MG, 18-0. [Structure indicates fatty acid at sn-1
      position - fatty acid at sn-2 position -carbohydrate component at sn-3 position
      of the glycerol molecule. ABBREVIATIONS: 20: 5, EPA; 16: 4,hexadecatetraenoic
      acid ; 16 : 1, palmitoleic acid ; MG, monogalactose ; DG, digalactose ; SQ,
      sulphoquinovose.]

PMID- 20050417
TI  - The true story behind Rosai-Dorfman disease.

PMID- 20050418
TI  - Yersinia pestis or: the dyschromatopsic flea.

PMID- 20050419
TI  - A study of 17 patients affected with plexiform neurofibromas in upper and lower
      extremities: comparison between different surgical techniques.
AB  - Plexiform neurofibromas (PN) are one of the most common and severe types of
      neurofibroma that occur in neurofibromatosis type I. These tumours affect long
      portions of nerves, infiltrating the nerve and surrounding tissue thus causing
      significant pain, deformity and functional problems in the affected part of the
      body. Treatment of this variant of neurofibromas is currently surgical. The aim
      of this study was to analyze the surgical treatment of plexiform neurofibromas in
      the lower and upper extremities. The clinical pathological features of 29
      neurofibromas, 12 in the upper extremities and 17 in the lower extremities, as
      diagnosed at the Department of Plastic and Reconstructive Surgery of University
      "La Sapienza" in Rome from 2000 to 2007, were reviewed. We established that
      subtotal and total resection without functional destruction is often possible for
      superficial PN.

PMID- 20050420
TI  - Reconstruction of defect after radical vulvectomy by the use of four-flap local
      transfer--a case report.
AB  - Malignant vulvar tumors must be treated by radical removal of the tumor as well
      as a sufficient amount of surrounding healthy tissue. The resulting defects can
      be resolved by skin transplants, local transfers, skin flaps, muscle flaps or
      free tissue transfers. We describe the case history of a patient who underwent
      radical vulvectomy for a malignant tumor with immediate reconstruction by local
      flaps from the area of inner thighs and mons pubis. The advantages and
      disadvantages of this method are compared to other reconstructive surgery
      methods.

PMID- 20050421
TI  - Laceration and degloving injury of a child's foot--a case report.
AB  - Laceration and degloving injury to a child's foot is quite a rare occurence,
      mostly resulting in persistent consequences. Treatment options for such an injury
      depend on the specific type of injury and the customary practice of each surgical
      department. The authors present the interesting case of 4-year-old boy with
      laceration and degloving injury to his right foot after a collision with a truck,
      suggesting simple treatment using skin graft which has an excellent functional
      and cosmetic effect. Several methods have been described in management of this
      kind of injury, such as microvascular free tissue transfer, free or local flap
      and skin graft. A full-thickness skin graft was used in this case with good
      result, and in our opinion this treatment option need not be reserved for plastic
      surgeons.

PMID- 20050422
TI  - New method of fixation in above-wrist replantation in patient with traumatic
      total carpal loss--a case report.
AB  - The incidence of above-wrist replantations is decreasing, mainly due to better
      working conditions and increased safety precautions. Osteosynthesis with a plate
      or external fixator is usually regarded as the gold standard of fixation. We
      present an unusual case of intramedulary fixation of both forearm bones to the
      2nd and the 5th metacarpal bone in the case of a patient with total carpal loss.
      This kind of fixation gives a satisfactory result with virtually no limitation of
      pronation and supination movements of the wrist.

PMID- 20050423
TI  - Nasal prosthesis supported with self-tapping implants with bioactive surface--a
      case report.
AB  - Nasal prosthesis using dental implants and magnetic abutments is a method of
      choice in replacement of missing hard and soft facial tissues. Nose form,
      coloration, and texture must be as indiscernible from the surrounding natural
      tissues as possible. Rehabilitation efforts can be successful only when patients
      can appear in public without fear of attracting unwanted attention. This case
      report evaluates on a step-by-step basis the materials and methods including
      implants insertion.

PMID- 20050425
TI  - Hospital reimbursement from all payers is at risk.

PMID- 20050424
TI  - If you thought the RACs were a pain, just wait for what's coming next.

PMID- 20050426
TI  - Documentation is the key when issuing HINNs.

PMID- 20050427
TI  - Follow-up calls help patients adhere to treatment plan, avoid readmissions.

PMID- 20050428
TI  - Throughput drive lowers discharge time, LOS.

PMID- 20050429
TI  - Hospital appeals, receives about $2 billion in denials.

PMID- 20050430
TI  - Studies show decrease in senior care continuity.

PMID- 20050431
TI  - Discharge often difficult at children's hospitals.

PMID- 20050432
TI  - Clarifying the role of the ESRD networks.

PMID- 20050433
TI  - Bundling, and what is important for patients.

PMID- 20050434
TI  - Electronic medical records are LEFT RIGHT in the middle.

PMID- 20050435
TI  - Vocational rehabilitation: is your facility on track?
AB  - BACKGROUND: The Conditions for Coverage for End-Stage Renal Disease Facilities
      require that facilities evaluate each patient for referral to vocational
      rehabilitation (VR) services, assist the patient in achieving and sustaining an
      appropriate level of productive activity, and develop a plan that reflects
      individual patient preference. Though research shows that people on dialysis who
      keep working feel better, data collected in the 2008 USRDS Comprehensive Dialysis
      Study indicates that only half of dialysis patients continued to work after
      starting treatment. OBJECTIVES: A review of the data and the reasons dialysis
      patients do not work provides an opportunity to identify resources and strategies
      to address barriers. FMQAI: The Florida ESRD Network (Network 7) initiated a
      quality improvement project in June 2008 to increase the percentage of Florida
      ESRD patients, aged 18 through 54, who were receivingVR services, attending
      school, or employed. METHODS: Using the 2007 ESRD Facility Survey (CMS-2744A)
      data as a baseline, Network 7 employed a two-pronged approach using both
      statewide spread efforts and focus group interventions with a targeted group of
      providers. All facilities identified in the focus group began the project with a
      baseline of 0% of patients ages 18-54 either engaged in VR, working, or in
      school. Quality improvement plan (QIP) workshops, conference calls, tracking
      tools, individualized facility data reports, educational materials, and technical
      assistance were utilized to improve VR rates in Florida. RESULTS: As of December
      31, 2008, Network 7 increased their statewide results (patients aged 18-54 either
      engaged in VR services, attending school or working) by 2.5% over the 2007
      baseline. For the focus group, as of June 30, 2009, results indicate that 40% of
      patients are either engaged in VR, working, or in school. RECOMMENDATIONS: By
      including VR in facility quality assessment and performance improvement (QAPI)
      activities, facilities can demonstrate outcomes-driven practice and enhance the
      independence and quality of life for ESRD patients.

PMID- 20050436
TI  - DaVita program advocates self-management of CKD.
AB  - The pilot study demonstrated facility-based, multidisciplinary team-based
      education adds significant value to educational practice. We continue to partner
      with nephrologists and other health care providers to encourage structured
      education programs, reach more patients to slow the progression of CKD, and
      manage public policy issues related to reimbursement so patients can receive
      necessary education. In a time when CKD education is being considered by public
      policymakers, it is important to demonstrate that there is value in not limiting
      CKD education to a specific population, and in providing that education through
      dialysis centers that already have the infrastructure in place to mount an
      effective, large-scale, standardized program.

PMID- 20050438
TI  - Obama's indirect effect on the diabetes community.

PMID- 20050444
TI  - Scotland forges ahead with new education agenda.

PMID- 20050445
TI  - Same-sex attraction: a model to aid nurses' understanding.
AB  - Young people attracted to people of their own sex are at risk of bullying and
      discrimination. It is often difficult for them to find support. Either
      emotionally or in relation to their health needs. This article explores a model
      to aid nurses in understanding the process individuals go through before coming
      to terms with their sexuality. The model also outlines the steps that nurses can
      take to enhance the care they provide for this vulnerable group of patients and
      clients.

PMID- 20050446
TI  - Nasogastric feeding for infants who have undergone palatoplasty for a cleft
      palate.
AB  - Almost 1,000 babies are born each year with some form of cleft, whether it is a
      palate, lip or a combination. However, with the advent of new regional cleft
      centres and specialist professionals caring for larger numbers of children with a
      cleft lip and palate, the long-term outcomes of these patients should show
      improvement. The nursing care on paediatric wards will make an important
      contribution to these outcomes. In this article, post-operative feeding,
      analgesia and inpatient stays following cleft palate repair are examined. In a
      post-palatoplasty study of 68 babies, 34 who were fed orally and 34
      nasogastrically, the babies who were fed nasogastrically were more settled,
      needed less analgesia and were discharged earlier. The parents of these babies
      were more relaxed knowing their child was fed and had adequate analgesia, and
      nurses believed they were able to give these babies a better quality of care.

PMID- 20050447
TI  - Safe transport from a specialist paediatric intensive care unit to a referral
      hospital.
AB  - There are 23 paediatric intensive care units (PICU) in the UK and 19 of these
      have a retrieval team responsible for the safe and uneventful transfer of
      critically ill children from referring hospitals. There are two established PICUs
      in University Hospitals of Leicester (UHL) NHS Trust that work as a team. In
      2001, a transfer service was introduced to support the UHL PICU retrieval service
      and the referring district general hospitals. At the time of writing this article
      there was no other PICU in the UK providing a dedicated paediatric clinical
      transport nurse service, whose main responsibility is the safe transfer of
      infants and children back to their local hospitals. This article will discuss the
      development of this service and the benefits to PICU and referral hospitals.

PMID- 20050448
TI  - Supporting mentors in clinical practice.
AB  - Students who entered training as of September 2007 are required to have a 'sign
      off mentor' in their final clinical placement to register with the Nursing and
      Midwifery Council. The sign-off mentor status is mandatory for confirming that,
      on completion of the final clinical placement, the student has met all the
      requirements of the pre-registration clinical assessment criteria and can
      register as a qualified nurse. This article describes the role of the clinical
      teacher in preparing and supporting mentors in one area of Wales.

PMID- 20050449
TI  - Illness as a predisposing factor to scalds in children: an exploratory study.
AB  - AIM: To explore whether the presence of illness is a predisposing factor to
      scalds in children aged five years and under. METHOD: A mixed methodology
      approach was used in this exploratory study. The results from the questionnaire
      phase are reported in this article. Questionnaires (n = 90) were sent out to the
      parents and carers of all children who had been admitted to a regional paediatric
      burns unit with scalds in the previous year. Both qualitative and quantitative
      data were collected. FINDINGS: These supported many of the findings in the
      literature. A typical child who had been scalded was a male toddler who was
      injured in the kitchen of his own home in the presence of a carer. Half of the
      children in this study were unwell around the time of the accident. CONCLUSION:
      Although this was a small pilot study, the need for parents and health carers to
      be vigilant is highlighted particularly when a child is unwell.

PMID- 20050450
TI  - The living donor: courage, character and commitment.

PMID- 20050451
TI  - Effects of hyperglycemia on the development of new-onset diabetes after liver
      transplantation.
AB  - CONTEXT: New-onset diabetes after transplantation (NODAT) has been associated
      with cardiovascular and thrombotic complications, acute rejection, and infection
      in transplant recipients. NODAT in kidney transplantation is well described;
      however, data are lacking in liver transplant recipients. OBJECTIVE: To evaluate
      the incidence of new-onset diabetes within 6 months postoperatively in adult
      liver transplant recipients. DESIGN, PARTICIPANTS, SETTING, AND INTERVENTIONS:
      Patients who underwent a liver transplantation at our institution between January
      2004 and December 2005 were retrospectively evaluated. NODAT was defined
      according to the diagnostic criteria of the American Diabetes Association/World
      Health Organization, persistent hyperglycemia (serum glucose > or = 200 mg/dL
      occurring 2 weeks after initial steroid induction and persisting for more than 2
      weeks), or the need for hypoglycemic agents upon discharge. MAIN OUTCOMES:
      Incidence of NODAT within 6 months after transplantation in patients with poor
      glycemic control within the first 2 weeks after transplantation, acute rejection
      episodes, infections, hospital readmissions, and cardiovascular and thrombotic
      events. RESULTS: Forty-five patients were evaluated. Within the first 6 months
      after transplantation, NODAT developed in 11 (24%). Acute rejection, infection,
      hospital readmissions, cardiovascular events, and thrombotic events did not
      differ between the groups. CONCLUSION: Elevated fasting levels of blood glucose
      during the first 2 weeks after liver transplantation may be associated with an
      increased incidence of NODAT and may have predictive value. More studies are
      needed to determine the effects of recognition and treatment of hyperglycemia in
      recent transplant recipients.

PMID- 20050452
TI  - Development of a survey to identify barriers to living donation in kidney
      transplant candidates.
AB  - BACKGROUND: Kidney transplantation from living donors, compared with deceased
      donors, has improved health care outcomes for patients with end-stage renal
      disease; however, less than 40% of transplants come from living donors. Numerous
      barriers may impede the identification of, and transplantation from, living
      donors. OBJECTIVE: To develop and validate a survey to identify barriers that
      transplant candidates may encounter when seeking a living donor for kidney
      transplantation. METHODS: The survey was developed in 3 phases: item
      identification by using persons with a stake in the process to identify key
      components; survey refinement, including assessment of content and face validity;
      and assessment of test-retest reliability by using the kappa coefficient and
      percent agreement for each of the scaled response items. RESULTS: The final
      survey contained 10 items with a Likert scale response and 5 open-ended
      questions. Expert nephrologists in the field confirmed face validity and content
      validity of the survey. The overall kappa coefficient for the scale was 0.76,
      reflecting excellent agreement, with an overall percent agreement of 88.7%.
      CONCLUSION: We developed a survey to identify barriers that kidney transplant
      candidates may experience when seeking a living donor, which demonstrated content
      and face validity as well as reproducibility. This survey can by used by endstage
      renal disease programs to identify barriers in candidates seeking a transplant.
      The results of the survey can be used to develop interventions to overcome such
      barriers with an ultimate goal of increasing rates of living kidney donation.

PMID- 20050453
TI  - Prevalence and correlates of influenza vaccination among kidney transplant
      patients.
AB  - CONTEXT: Immunosuppressive regimens increase kidney transplant patients' risk of
      contracting life-threatening influenza. However, little information exists about
      the prevalence and correlates of influenza vaccinations in this population.
      OBJECTIVE: To determine the prevalence and explore correlates of influenza
      vaccination in kidney transplant recipients. DESIGN, SAMPLE, AND SETTING: This
      cross-sectional study used data from the Supporting Medication Adherence in Renal
      Transplantation study. The convenience sample consisted of 356 adult kidney
      transplant recipients (58.1% male; mean age, 52.9 [SD 13.53] years) recruited
      from 2 Swiss transplant outpatient clinics. Influenza vaccination status was
      assessed by self-report (yes/no). MAIN OUTCOME MEASURE: Known correlates of
      vaccination in chronically ill patients (older age, cohabitation, higher
      education, higher socioeconomic status, financial stability, more comorbid
      diseases, nonsmoking status, and clinical site where care is received) were
      entered into a multiple logistic regression model. RESULTS: Of the 356 patients,
      only 83 (23.3%) reported having been vaccinated against influenza in the previous
      year. Positive vaccination status was significantly related to older age (odds
      ratio, 1.04; 95% confidence interval, 1.02-1.06). CONCLUSION: Despite national
      and international guidelines recommending influenza vaccination in kidney
      transplant recipients, the prevalence of influenza vaccination in this sample was
      low. This study's results suggest that transplant centers need to implement
      policies to maximize influenza vaccination of their patients.

PMID- 20050454
TI  - Caregivers' perspectives on decision making about lung transplantation in cystic
      fibrosis.
AB  - CONTEXT: Lung transplantation extends survival for some patients with advanced
      cystic fibrosis, but it is complicated, has many potential risks, and its
      outcomes are difficult to predict. No standards exist for informed decision
      making about transplantation. OBJECTIVE: To assess decision making from the
      perspective of caregivers of patients who faced the transplant decision before
      dying of cystic fibrosis or transplant complications. DESIGN: Semistructured
      interviews with descriptive and qualitative content analysis. PARTICIPANTS:
      Twenty-eight caregivers of patients with cystic fibrosis who received care at our
      center and died between 1996 and 2006. RESULTS: Of 28 patients who considered
      lung transplantation, 19 (68%) received transplants, 6 (21%) died while waiting
      for transplant, and 3 (11%) declined transplant. Three caregivers (11%) thought
      that the patient did not fully understand the reason for transplant referral.
      Five (18%) thought that the patient did not fully understand potential risks. Ten
      (36%) thought that alternatives were not fully understood. The only alternatives
      to transplant identified, progressive illness and the possibility of earlier
      death without transplant, were unacceptable to most. Thirteen caregivers (46%)
      reported that the patient thought that declining transplant was not an option.
      Caregivers described the decision as "easy" for 19 (68%), often expressing a
      sentiment of "do or die." Those who described the decision as "easy" recalled
      fewer elements of informed decision making. CONCLUSIONS: From caregivers'
      reports, patients with cystic fibrosis may not fully understand risks of and
      alternatives to lung transplantation. Because a strong desire to prolong life
      necessitates honest communication about potential outcomes, interventions are
      needed to facilitate high-quality decision making.

PMID- 20050455
TI  - One kidney transplant center's experience: linking process improvements and
      Medicare/Medicaid conditions of participation.
AB  - CONTEXT: An institutional priority toward transplantation, dedicated team
      dynamics, aggressive clinical growth, and optimal care practices are essential
      for delivering exceptional care to transplant patients. The importance of
      multidisciplinary integration of these priorities throughout the continuum of
      patient care is widely recognized in the transplant arena as well as by the
      Centers for Medicare and Medicaid Services (CMS). In fact, it is the
      collaboration within these aspects of care that is necessary for certification by
      CMS. OBJECTIVES: To establish institution-wide practices, systems, and mechanisms
      to optimize performance of transplant centers through the use of evidence-based
      protocols, clinical innovation, and data-driven quality improvements. To develop
      training programs and competency based orientation addressing the topics needed
      for transplant nurses, multidisciplinary caregivers, and clinical transplant
      coordinators who provide care to transplant patients. To comply with the CMS
      conditions of participation for transplant centers. METHODS: Formation of a renal
      transplant council and multidisciplinary care team. Flow chart of hospital course
      from admission to discharge, carefully examining patients' progression through
      the continuum of care, assessing for barriers to care and knowledge deficits of
      transplant practitioners. RESULTS: Development of multiple clinical process
      improvements resulting in the creation of an environment for continuous learning,
      optimal transplant care, and exceptional outcomes in transplantation as well as
      compliance with CMS conditions of participation for transplant centers.

PMID- 20050456
TI  - Induction immunosuppression for orthotopic heart transplantation: a review.
AB  - OBJECTIVES: To describe the appropriateness and safety of induction
      immunosuppression for patients at risk for fatal rejection, and to describe the
      safety and effectiveness profiles of the induction regimens available in the
      United States. DATA SOURCES: MEDLINE/PubMed database, EMBASE database, Google
      Scholar; references from pertinent articles were also reviewed to identify
      additional data. STUDY SELECTION: A systematic literature review from January 1,
      1980, through June 30, 2008, was performed. Included articles ranged from case
      series to prospective randomized controlled double-blind placebo-controlled
      trials that detailed the following topics with respect to induction
      immunosuppression: risk of fatal rejection, renal sparing, malignancy, OKT3,
      rabbit or equine antithymocyte globulin, daclizumab, basiliximab, and
      alemtuzumab. RESULTS: Patients at highest risk for fatal rejection experienced a
      survival benefit from induction immunosuppression, whereas all other patients
      experienced no benefit or harm. Most of the early data detail positive
      experiences with polyclonal antibody regimens. Several newer trials compare the
      use of polyclonal strategies with the use of anti-CD25 targeted monoclonal
      antibodies. Few researchers have assessed the usefulness of an anti-CD52
      approach. Overall, induction therapy remains a poorly studied and widely variable
      practice among the major US heart transplant centers. CONCLUSION: At present, the
      unrestricted use of induction for all patients does not seem prudent. Induction
      should be individualized for each patient on the basis of a well-designed
      protocol, careful analysis of the transplant center's demographics, and the
      effectiveness and safety profiles of the regimens used.

PMID- 20050457
TI  - Teaching organ and tissue donation in medical and nursing education: a needs
      assessment.
AB  - CONTEXT: Research on organ donation education is limited by its reliance on
      convenience samples (ie, small sample sizes and local schools) and its failure to
      assess methods of instruction on the topic. OBJECTIVE: To describe medical and
      nursing students' training in organ donation by examining curriculum content and
      methods of instruction by using a national sample of medical schools and a
      statewide sample (New York) of nursing schools. DESIGN: Self-report online
      survey. PARTICIPANTS: Nursing and medical deans responsible for curriculum
      development and evaluation. MAIN OUTCOME MEASURE: Participants provided
      information on the inclusion of specific topics in organ donation, skills related
      to organ donation, and the declaration of personal donation intentions within
      their respective educational programs. Methods of instruction on such topics (eg,
      standardized patients, lectures, small groups) also were assessed. RESULTS:
      Although many educational programs include an organ donation component, a
      significant proportion of schools failed to provide instruction on donation
      consent processes, definitions of brain and cardiac death, and the discussion of
      organ donation during a routine health care visit. Most schools rely on lectures
      as the sole method of instruction. Recommendations are made for how deficits in
      instruction might be addressed through future interventions and education.

PMID- 20050458
TI  - Traumatized liver grafts for organ donation? A single-center experience.
AB  - Because the number of patients on waiting lists increases each year, new
      strategies are urgently needed to expand the donor pool. The use of traumatized
      donor livers for orthotopic liver transplantation at a transplant center is
      described. After transplantation, no increased incidence of perioperative
      complications such as bleeding, bile leakage, or liver graft dysfunction were
      observed and the transplanted livers exhibited appropriate long-term function.
      Thus, the use of injured livers may offer new opportunities in transplantation.

PMID- 20050459
TI  - Stability of levothyroxine sodium 0.4 microg/mL in 0.9% sodium chloride
      injection.
AB  - CONTEXT: Intravenous levothyroxine therapy decreases vasopressor requirements and
      prevents cardiovascular collapse in hemodynamically unstable patients eligible
      for organ donation. The stability of levothyroxine when used in this manner is
      unknown. OBJECTIVE: To determine the stability of levothyroxine solution for
      intravenous use at a concentration of 0.4 microg/mL diluted in 0.9% sodium
      chloride. DESIGN: Triplicate sample sets were prepared by reconstituting
      levothyroxine 200 microg for injection with 5 mL of 0.9% sodium chloride with
      further dilution in 500 mL of 0.9% sodium chloride. One sample set was protected
      from light and the other was left unprotected. Both sample sets were stored at
      room temperature, and samples from each were analyzed for initial concentration
      and 4, 8, 12, and 24 hours later. CONCLUSIONS: Levothyroxine sodium 0.4 microg/mL
      in 500 mL 0.9% sodium chloride is stable for 24 hours at room temperature when
      protected from light.

PMID- 20050460
TI  - Family, friends, and faith: how organ donor families heal.
AB  - CONTEXT: Understanding how organ donors' families recover from their grief can
      help organ procurement organizations improve consent rates and increase the
      number of deceased donor organs available for transplant. OBJECTIVE: To determine
      what helps the loved ones of deceased organ donors heal from their grief and
      loss, and to better understand families' needs during the consent process as a
      way of improving overall consent rates for organ donation. DESIGN, SETTING, AND
      PARTICIPANTS: Written survey of all organ and tissue donors' families in the San
      Diego and Imperial County (California) service area during 2006 and 2007. MAIN
      OUTCOME MEASURES: Responses to the 20-question survey addressing factors that
      help healing from grief, as well as contextual information about the families'
      experience at the hospital and the consent process. RESULTS: Most respondents
      (84%) indicated that family support was the most helpful thing in dealing with
      their grief, followed by the support of friends (74%) and religious and cultural
      beliefs (37%). Most (75%) indicated that they agreed to donation so that
      something positive could result from their loss. Most respondents (93%) felt that
      they were given enough information to make an informed decision about donation,
      and 6% indicated that the donation process interfered with funeral or memorial
      arrangements. More than 95% understood that their loved one had died before they
      were approached for consent. Consistent with previous studies, 12% said they
      still had unanswered questions about aspects of donation, and 15% of respondents
      indicated that the discussion about organ donation added more emotional stress to
      their overall experience.

PMID- 20050461
TI  - Pelvic kidney in organ donation: case study.
AB  - An ectopic kidney is a rare congenital anomaly that occurs when the kidney fails
      to ascend to its normal position. Often an ectopic kidney is asymptomatic and the
      kidney is an unexpected finding during organ recovery. The kidney described in
      this case report had normal function and could have been used for
      transplantation, if it had been recovered without 2 renal arteries being damaged
      because of anatomic variation. The renal vasculature in this type of abnormality
      usually ascends from the iliac vessels, and this variation in anatomy should be
      taken into consideration by the recovering surgeon during arterial cannulation
      for organ flushing.

PMID- 20050462
TI  - Kidney donation and transplantation in Eurotransplant 2006-2007: minimizing
      discard rates by using a rescue allocation policy.
AB  - CONTEXT: All organ exchange organizations are challenged to maximize the
      utilization rate of all donors. OBJECTIVE: To investigate the benefit of a rescue
      allocation policy and to study the impact of donor factors on the risk of kidney
      discard. DESIGN AND SETTING: All 4057 donors with kidneys offered for allocation
      to Eurotransplant between 2006 and 2007 were included. Allocation was patient
      oriented, based on a point-score system including recipient and donor factors. If
      an organ offer was rejected 5 times for medical reasons, allocation was switched
      to rescue allocation (ie, the organ was then offered in a center-oriented way). A
      logistic regression model was built to test whether donor factors were predictors
      of rescue allocation or kidney discard. RESULTS: Rescue allocation was used for
      665 donors (16.4%); within this group, transplant rate was 54.3%, resulting in a
      donor discard rate of 304 donors (7.5% of total study group). The multivariate
      model showed that rescue allocation was used significantly more for kidneys from
      child donors and donors with a high creatinine level. Moreover, testing positive
      for hepatitis B surface antigen or antibody to hepatitis C virus was associated
      with an increased probability of rescue allocation. Kidney discard was
      significantly associated with donation after cardiac death, donor age, serum
      creatinine level, history of diabetes, and history of hepatitis. CONCLUSIONS:
      Rescue allocation is effective in lowering donor discard rates. Even with rescue
      allocation, several donor factors were significantly associated with a higher
      discard rate. Use of liberal donor criteria and a rescue allocation policy can
      reduce kidney discards and thus shorten the waiting list for kidney
      transplantation.

PMID- 20050463
TI  - Attitude of nursing staff toward organ donation in a Spanish hospital with a
      solid-organ transplant program.
AB  - CONTEXT: Nursing personnel are fundamental in the organ donation and
      transplantation process, and their attitude toward donation has a decisive effect
      on patients, patients' families, and the general public. OBJECTIVE: To analyze
      the attitudes of nursing personnel toward donation in a transplant hospital and
      the factors that determine those attitudes. MATERIALS AND METHODS: A random
      sample of 305 nurses in different hospital services was taken and stratified by
      type of service. A validated psychosocial questionnaire was used to evaluate
      attitudes toward donation. The survey was completed anonymously and was self
      administered. Student t test, chi2 test, and logistic regression analysis were
      used for statistical analysis. RESULTS: Most respondents (63%) favored organ
      donation. The following variables affected attitude: (1) having a favorable
      attitude toward donation of a family member's organs (P < .001), (2) knowing the
      concept of brain death (P < .001), (3) having discussed organ donation and
      transplantation within the family (P = .001), (4) having a favorable attitude
      toward autopsy (P = .006), (5) fearing mutilation of the body (P < .001), (6) a
      partner's attitude toward organ donation and transplantation (P < .001), and (7)
      the respondent's religion (P = .009). Multivariate analysis yielded the following
      significant factors: (1) fear of mutilation of the body (odds ratio, 9.5), (2)
      partner's attitude toward organ donation and transplantation (odds ratio, 0.2),
      and (3) respondent's religion (odds ratio, 2.7). CONCLUSIONS: Attitudes toward
      organ donation among nurses are similar to attitudes of the general public in
      Spain. Given the influence of nurses on the general public, promotional campaigns
      directed at nurses are a priority.

PMID- 20050464
TI  - Top nurse warns risk tools are not backed by evidence.

PMID- 20050465
TI  - Managers must support nurses to boost their commitment to care.

PMID- 20050466
TI  - See the person in the health professional: how looking after staff benefits
      patients.
AB  - The Point of Care programme at The King's Fund held its first national conference
      last month. A central theme was the importance of staff experience in improving
      quality. Here we explore the reasons why staff experience is important and
      propose practical tips for trusts to support employees. Where staff experience is
      good, patients' experience is more likely to follow suit.

PMID- 20050467
TI  - Depression in adults with long term conditions 1: how to identify and assess
      symptoms.
AB  - The first in this two part unit on depression in adults with long term conditions
      examines new NICE guidance on identifying and managing this mental health
      problem. It discusses the prevalence and causes of depression in this group, how
      to identify and assess the condition, and initial management options for those
      with subthreshold/mild to moderate symptoms.

PMID- 20050468
TI  - NICE guidance to reduce variations in immunisation rates and maximise uptake.

PMID- 20050469
TI  - The risks associated with consumer magazines giving advice on complementary
      therapies.
AB  - BACKGROUND: The increased popularity of complementary and alternative medicine
      (CAM) has led to increased demand for information on it, giving rise to the
      concept of "new experts". However, there is concern about the quality and
      accuracy of this information, much of which is published in popular magazines and
      written by contributors with no medical qualifications. AIM: To examine the
      extent of CAM product advice in women's and health magazines, and the potential
      for adverse drug/herbal interaction. METHOD: Fifteen women's magazines were
      examined over one month. RESULTS AND DISCUSSION: A total of 150 articles were
      identified, of which 131 were written by non-medically qualified contributors,
      mainly journalists. Out of the 150, 95 discussed ingested herbs which had the
      potential for adverse interactions and are contraindicated for certain groups.
      CONCLUSION: The findings have legal and ethical implications. The re-evaluation
      of the journalists' code of conduct to reflect this development in journalism
      should be considered.

PMID- 20050470
TI  - The menopause: effects on the pelvic floor, symptoms and treatment options.
AB  - This article discusses the effects of age and the menopause on the pelvic floor,
      subsequent risks of urogynaecological dysfunction, symptoms of this dysfunction
      and treatment options.

PMID- 20050471
TI  - Desperate times call for inventive measures.

PMID- 20050472
TI  - More policing of trusts will not improve standards.

PMID- 20050473
TI  - A question of regulation.

PMID- 20050474
TI  - Winning ways of first-class sister. Interview by Jennifer Sprinks.

PMID- 20050475
TI  - Coping with on-site fires is burning issue for managers.

PMID- 20050477
TI  - At breaking point: the NHS funding crisis.

PMID- 20050478
TI  - How to keep score of acuity and dependency.
AB  - This article describes how the introduction of an acuity and dependency tool at
      University Hospitals Coventry and Warwickshire NHS Trust has provided nurses with
      a structure for gathering evidence about patient care levels, and discusses how
      this information is shared throughout the trust to improve patient outcomes and
      safety.

PMID- 20050479
TI  - In search of inspired ideas for improving patient care.
AB  - The Health and Social Care Awards were launched to celebrate the excellent or
      innovative work of front line healthcare staff. This article previews the ninth
      award ceremony next year and highlights two of the winners from this year.

PMID- 20050480
TI  - Calculating skill mix: implications for patient outcomes and costs.
AB  - Debate continues about the hierarchy of skilled roles in the nursing workforce.
      For example, should there be grades of qualified nurses other than registered
      nurses? Should all registered nurses be prepared to degree level? And to what
      extent should the nursing workforce comprise staff who are not qualified as
      nurses? Such questions raise critical issues about how different configurations
      of staff affect patient care outcomes and whether judgements can be made about
      their cost effectiveness. This Policy+ article refers to systematically reviewed,
      international evidence in considering the implications for UK nursing of the
      inclusion of a second-level qualified nurse in the skill mix of the nursing
      workforce.

PMID- 20050481
TI  - Pre-registration nursing education standards out for consultation.
AB  - The Nursing and Midwifery Council is developing new standards for pre
      registration nursing education. This article discusses the areas in which
      significant changes to the existing standards are to be made and outlines what
      these changes may mean for the workforce, particularly mentors and managers.

PMID- 20050482
TI  - Role of clinical nurse leadership in improving patient care.
AB  - Leadership in nursing plays a crucial part in the provision of good patient care.
      However, the terms 'nursing leadership' and 'nursing management' are often
      confused. This article discusses the difficulties in defining 'clinical
      leadership', outlines its development in the Republic of Ireland, and identifies
      issues that must be addressed if clinical nurse leaders are to be effective.

PMID- 20050483
TI  - Improved record-keeping with reading handovers.
AB  - Nursing handover has traditionally been performed orally and apart from patients.
      Results of an audit undertaken at the Royal United Hospital, Bath, suggest that
      record-keeping standards there were poor. To improve these standards, a method of
      'reading handover', in which the main method of communication between nurses on
      different shifts is written rather than oral, was introduced on one ward. This
      article discusses the results of this pilot study and suggests that the new
      handover method has improved standards of record keeping.

PMID- 20050484
TI  - Academic exercise.

PMID- 20050485
TI  - Moral courage or moral imperative: which is it?

PMID- 20050486
TI  - The Clinical Nurse Leader: impact on practice outcomes in the Veterans Health
      Administration.
AB  - The Clinical Nurse Leader (CNL) role was designed to meet an identified need for
      expert clinical leadership at the point of care. The Veterans Health
      Administration (VHA) became early adopters of the CNL role, foreseeing the value
      of this pivotal clinical leader at the point of care to meet the complex health
      care needs of America's veterans and shape health care delivery. Impact data were
      collected and assimilated from seven Veterans Administration Medical Centers to
      support how CNLs impact the delivery of quality and safe patient care and how
      practice changes could be sustained. Data collection and analyses resulted in
      many lessons learned. The new CNL role was implemented in a variety of settings
      in the VHA system. Integration of the CNL role in all areas of practice in every
      care setting has the promise of streamlining coordination of care for veterans
      across all spectrums in the provision of care.

PMID- 20050487
TI  - Registered nurses' perceptions of nurse staffing ratios and new hospital payment
      regulations.
AB  - Two regulatory initiatives weigh heavily on the nursing workforce: establishing
      minimum patient-to-nurse staffing ratios in hospitals and payment policy that
      eliminates payment to hospitals for negative consequences of care. Although the
      majority of RNs favor ratios, results also indicate that a good number of RNs
      either do not support ratios or are unsure, which suggests that while strong
      support for ratios exists, the support is not universal. With regard to the
      Centers for Medicare and Medicaid Services hospital payment regulations, while
      many RNs expect that this policy change will increase the emphasis on prevention
      and additional education and training, RNs also believe they will be blamed if
      adverse patient conditions occur. A clear majority think that their work will
      increase, and only a small percentage of RNs think the regulations will lead to
      added respect, more staffing, higher pay, or raise their status. Beyond affecting
      the clinical environment, both regulations will impact RNs' economic value in the
      eyes of the hospitals that employ them.

PMID- 20050488
TI  - New graduate burnout: the impact of professional practice environment, workplace
      civility, and empowerment.
AB  - The future of professional nursing depends on finding ways to create high-quality
      work environments that retain newcomers to the profession. The purpose of this
      study was to examine the combined effect of supportive professional practice
      environments, civil working relationships, and empowerment on new graduates'
      experiences of burnout at work. The results support previous evidence of the
      importance of working environments that enable new graduates to practice
      according to professional standards learned in their educational programs.
      Further, the results provide a more comprehensive understanding of the impact of
      workplace conditions on new graduate burnout by demonstrating the additive value
      of working in collegial work settings in which nurses respected others and
      refrain from incivility behaviors in their day to day work. Given the current
      nursing shortage, every effort must be made to ensure that new graduates are
      exposed to high-quality work environments that engage them with their work.

PMID- 20050489
TI  - Recruitment and retention of nurse educators: a pilot study of what nurse
      educators consider important in their workplaces.
AB  - To better understand the nature of a quality practice environment for nurse
      educators, a survey instrument was constructed and pilot tested. he aim of the
      study was to highlight some of the critical issues needing to be addressed to
      support the recruitment and retention of nurse educators. The knowledge generated
      from the survey makes explicit what nurse educators consider to be important to
      them in their environments and whether they are currently experiencing these
      elements. Based on the preliminary results, additional research needs to be
      undertaken to further develop the psychometric properties of the tool along with
      a closer examination of the culture of schools of nursing. The information
      generated may serve to enhance nurse educators' environments to better reflect
      what they consider to be important.

PMID- 20050490
TI  - Economic evaluation of pressure ulcer care: a cost minimization analysis of
      preventive strategies.
AB  - The purpose of this study was to determine the cost for prevention and treatment
      of pressure ulcers from a hospital perspective and to identify the least resource
      intensive pressure ulcer prevention strategy. Cost analyses were examined from a
      hospital perspective using direct costs. The study was carried out alongside a
      prospective cohort study on the incidence and risk factors for pressure ulcers.
      Two large teaching hospitals in the Netherlands with (partly) opposing approaches
      in prevention, a technological versus a human approach, were analyzed. The main
      outcome measures were resource use, costs of preventive measures and treatment,
      and pressure ulcer incidence in both hospitals. Pressure ulcer prevention through
      a predominantly technical approach resulted in a similar incidence rate as
      prevention through a predominantly human approach. However, the technical
      approach was considerably less expensive.

PMID- 20050491
TI  - A study of a nursing department performance measurement system: using the
      Balanced Scorecard and the Analytic Hierarchy Process.
AB  - The health care industry is under pressure from government and private entities
      as well as from market conditions to contain costs. In an effort to respond to
      these pressures, the case hospital in this study implemented a Balanced Scorecard
      (BSC) in January 2003 and integrated it with the hospital's formal incentive plan
      for non-physicians in January 2005. The nursing department's performance improved
      in the 2 years following the introduction of the plan. This study contributes to
      the literature by demonstrating the performance improvement that results from
      integrating the BSC with an incentive plan in the nursing field. The results
      provide insight into the current BSC performance metrics applied by the case
      nursing department, and could be used as guidelines by other health care
      organizations that wish to implement BSC-based incentive plans.

PMID- 20050492
TI  - Growing ambulatory care nurse leaders in a multigenerational workforce.
AB  - Ambulatory care faces challenges in sustaining a nursing workforce in the future
      as newly licensed nurses are heavily recruited to inpatient settings and
      retirements will impact ambulatory care sooner than other areas. Building a
      diverse team by recruiting nurses of different ages (generations) and skills may
      result in a more successful and robust organization. Knowledge about generational
      characteristics and preferences will aid nurse leaders and recruiters in
      attracting high-quality, talented nurses. Nurses of Generations X and Y can
      increase their likelihood of success in ambulatory care by better understanding
      intergenerational issues.

PMID- 20050493
TI  - An interview with health economist and labor expert Joanne Spetz, PhD. Interview
      by Peter I Buerhaus.

PMID- 20050494
TI  - Getting real on evidence-based staffing.
AB  - Getting your arms around the topic of evidence-based staffing is not simple.
      There is no central place where one can turn to understand what evidence-based
      staffing is, what is necessary to adopt it, and how to measure its effectiveness.
      Organizing the evidence into usable resources and tools that can provide the
      guidance and experience needed to successfully operationalize evidence-based
      staffing is perhaps our biggest barrier. It was against this backdrop that a
      model for evidence-based staffing was developed through a national collaborative
      effort. While change is never easy, it is feasible that letting go of the gross
      inefficiencies, habits, traditions, policies, and practices that will be replaced
      by evidence-based staffing will not be so hard. With the movement grounded in
      science and guided by experience and wisdom, it seems safe to assume that we can
      get there quickly.

PMID- 20050495
TI  - Health care reform: through the lens of change.
AB  - Change theory concepts--drivers, vision, current and future states, and social
      buy-in--provide some analytical leverage in understanding current reform
      challenges. Various contentious issues in the health care reform battle have long
      served to polarize stakeholders and differentiate conservative and liberal
      positions. Successful change efforts are led by the development of a compelling
      vision, which has certain attributes. Change theory postulates that if there is
      not strong dissatisfaction with the current state, the future state is less
      feasible. Social systems change theory is another way to conceptualize and
      broaden our understanding of health policy as a form of social change, how
      environmental or external forces influence policy design, and how the ongoing
      media presentation of a policy influences direction of the outcome.

PMID- 20050496
TI  - Denial and immunity to change: it starts with the leader.
AB  - It is common for leaders to be confronted with resistance that makes forward
      progress impossible. The easiest action for the leader is to label the resistance
      as denial. Labeling behaviors that do not agree with expectations is one way
      leaders keep their immune system intact and fight off valuable feedback. The
      enlightened, well-developed leader is aware of her/his own immune system and can
      monitor the filtering system effectively. We have many opportunities to help
      organizations and leaders think through the roadmap that makes our immune systems
      switch off when new, helpful information is trying to enter.

PMID- 20050497
TI  - [The future of the nursing discipline in the Italian University].
AB  - In a period of important reforms of the Italian University system, problems and
      challenges and the impact of changes on the development of the nursing discipline
      in the university are analyzed.

PMID- 20050498
TI  - [Cohort study of the incidence of heel pressure sores in patients with leg casts
      at the Rizzoli Orthopedic Hospital and of the associated risk factors].
AB  - INTRODUCTION: Pressure sores, especially at the heel, are a side effect of the
      cast. AIM: To assess the incidence of late skin complications (heel pressure
      sores) of a cast and determine risk factors. METHODS: All consecutive patients
      treated with a leg cast over a 16 months observation time were recruited. Risk
      factors were identified by the nurse that placed the cast and skin lesions
      classified with the NPUAP scale when the cast was removed. RESULTS: In the 216
      enrolled patients 17.6% (38) developed a pressure sore: 16/124 in orthopedic
      wards; 22/92 in oncology wards. The multivariate analysis identified the
      following risk factors: administration of cytotoxic drugs (p = 0.033; OR = 2.61;
      having a cancer did not increase the risk); skin redness before cast application
      (p = 0.001; OR = 4.44) and having reported symptoms after the application (p =
      0.000; OR = 7.86). Pressure sores were mainly stage 1 and only 6/216 (2.4%) > or
      = stage II. The type of plaster cast, the material, the number of days it was
      worn and having had a surgery are not significant risk factors. CONCLUSIONS:
      Pressure sores related to leg plaster casts are a frequent complication in at
      risk sub-groups. The acknowledgement and identification of specific risk factors
      may allow to identify and evaluate preventive interventions to improve the care
      of these patients.

PMID- 20050499
TI  - [Modifications of vital signs during hygiene care in intensive care patients: an
      explorative study].
AB  - Hygiene care in critical patients may alter vital signs. Aim of this paper is to
      measure vital signs and their modifications in critical patients during hygiene
      care and measure differences with pre and post hygiene values. METHOD: Vital
      signs of 6 patients two hours before, during and 90 minutes after hygienic care
      were measured. RESULTS: During and 2 hours after the end of hygiene a
      modification of vital signs was observed compared to basic values (mean values
      during/90 min after, compared to baseline): heart rate +11.20%/ +1.48; systolic
      blood pressure +22.68%/+1.56; arterial capillary saturimetry -4.31/+0.27,
      Respiratory frequency +8.10/+2.66, tidal volume +4,04/-7,51, CO2 min/vol +5,34/-
      22.33, bladder temperature -0.85/-0.60. CONCLUSIONS: Hygiene care in critical
      care patients may significantly alter vital signs. Therefore a strict
      haemodinamic and respiratory monitoring is warranted as well as protocols for the
      management of sedation and of vasoactive support.

PMID- 20050500
TI  - ["Diabetes is for me ...": the health care workers perspective].
AB  - AIM: To analyze the representations and meanings of diabetes from the health
      workers perspective through an ethnographic approach. METHOD: Participants who
      attended a national conference on diabetes care were asked to write a narrative
      responding to the question: "For me, diabetes is...". Narratives were
      qualitatively analyzed by two researchers following the principles of content
      analysis. Nvivo software was used to organize and code the data. RESULTS: Of the
      147 conference participants, 140 narratives were analyzed: 86 written by nurses,
      54 by physicians. Six themes emerged: The disease which summarizes the biomedical
      and biopsychosocial definitions of diabetes; The patient's illness experience,
      which describes the impact of diabetes on the patients lives; The clinician's
      experience, where clinicians fear the impact (actual or potential) of diabetes on
      their families or themselves; The clinician-patient relationship, where the
      importance of a good patient-clinician relationship and the related emotions are
      described; and The social and healthcare system, which describes the healthcare
      system as an aid as well as an obstacle in patients' care. CONCLUSION: Despite
      some academic description of diabetes, our results showed that health care
      workers, especially nurses, have a profound comprehension of the patient illness
      experience that sometimes leads to the identification with patients. The
      relationship and patient education were described as a complex and challenging
      area of practice for both professions. Training on relational and emotional
      skills could improve the patients care.

PMID- 20050501
TI  - [When the daily chronicles coincide with the most "hard" epidemiology: the case
      of migrants to Europe].
AB  - The migration from Africa to Europe has become one of the most dramatic
      situations of the violation of fundamental rights of the first decade of the new
      millennium. METHODS: As the official source of epidemiology do not recognize the
      data of peoples who die and/or disappear while trying to reach European borders,
      only "informal" sources can be used to trace the fate of this populations. A
      Mediterranean Observatory called Fortress Europe (http://fortresseurope.
      blogspot.com) has emerged over the last several years as a reference
      documentation centre for this controversial areas. RESULTS: The tables which
      summarize some of the most striking data on mortality and disappearances are
      presented and commented as examples of how real life epidemiology cannot be
      considered a specific or exclusive medical discipline. CONCLUSION: Human rights
      must increasingly be considered one of the key measures and indicators of the
      joint priorities of societal and health care systems.

PMID- 20050502
TI  - [Should Allen test be performed before radial artery cannulation?].
AB  - The Allen test is performed to assess the circulation of the hand. It's
      reliability has been questioned in several studies. The results of a review are
      reported: the criteria of an abnormal Allen test are not agreed on and performing
      it cannot be considered standard care.

PMID- 20050503
TI  - [Materials for an epidemiology of migration].
AB  - The data on the international migration worldwide and in Italy are presented and
      discussed, not only from the specific point of view of health conditions, but
      also by framing their "health burden" in the broader context of their
      contribution to the Italian economy.

PMID- 20050504
TI  - MSD: Delaware's home for a healthy tomorrow.

PMID- 20050505
TI  - Letter from the Capital Campaign Chair.

PMID- 20050507
TI  - Contribution guidelines.

PMID- 20050506
TI  - The case for the Medical Society of Delaware's purchase and renovation of the
      Bowman Conference Center. "Delaware's home for a healthy tomorrow".

PMID- 20050508
TI  - Capital campaign donor recognition opportunities.

PMID- 20050509
TI  - Tax-advantaged ways to fulfill your charitable intentions.
AB  - The Medical Society of Delaware has invited this article to provide its members
      and potential donors with guidance on ways in which tax-advantaged contributions
      may benefit both the donor and the Medical Society's capital campaign,
      "Delaware's Home for a Healthy Tomorrow." Donations to the capital campaign
      should be directed to the Society's subsidiary, Delaware Medical Education
      Foundation, a 501(c)(3) organization, fully qualified for charitable
      contributions.

PMID- 20050510
TI  - Engaging in crucial conversations.

PMID- 20050511
TI  - Shared governance: enhancing nursing practice.

PMID- 20050512
TI  - Pictures and perspectives: a unique reflection on interdialytic weight gain.
AB  - The purpose of this study was to explore the perspectives of managing
      interdialytic weight gain for individuals on hemodialysis. A qualitative design
      was used to elicit patients' stories with some participants using images to
      support their story telling. Data were analyzed using an iterative theming
      process. Themes that arose from preliminary data analysis include magnitude of
      loss, constant struggle, and transition to acceptance. Transition to acceptance
      is not a linear progression to understanding and compliance but a multifaceted,
      tortuous struggle unique to individuals and largely dependent upon support,
      belief in a life worth living, and willingness to engage in surveillance and
      maintenance of behavior. Appreciating the impact and meaning of fluid restriction
      for individuals on hemodialysis will assist health professionals to identify
      support strategies that facilitate healthy fluid gain behaviors.

PMID- 20050513
TI  - African-American women's perceived health status while caring for a relative with
      end stage renal disease.
AB  - This study describes health status, health status changes, and factors predicting
      perceived health status of 75 African-American women caring for relatives with
      end stage renal disease. One-third of participating caregivers rated their health
      as fair or poor; others reported good health. Increased worry, mood changes, and
      stress/tension were problematic. Numbers of prescription medications, physician
      office visits in the past 6 months, and health problems- along with caregiver age
      and depression total score-explained 31% (p = 0.000) of total variance in
      perceived health status. This caregiver population would benefit from health
      promotion interventions.

PMID- 20050514
TI  - Lethality of endocarditis due to S. aureus among patients on hemodialysis.
AB  - This study evaluated the prevalence and risk factors for endocarditis in patients
      undergoing hemodialysis with central venous catheter (CVC) and to identify the
      microorganisms isolated from the bloodstream. This cohort study followed 94
      patients with end stage renal disease (ESRD) who developed bacteremia after the
      insertion of a CVC for dialysis in the hospital Sao Paulo, UNIFESP, Brazil. They
      were divided into two groups: patients with endocarditis (E+) and patients
      without (E-). The prevalence of endocarditis was 29%. Among risk factors, the
      time of hospitalization and residence of the catheter were significantly higher
      (p < 0.001) in group E+. The mortality rate was 15%, and lethality of
      endocarditis was 55%. Of the 38 microorganisms isolated in group E+, 20 were S.
      aureus and 45% of those were MRSA. Group E+ with MRSA presented 100% mortality.
      High mortality and lethality in the E+ group was observed, and of the
      microorganisms isolated, MRSA was the most lethal. This article provides an
      overview of the findings of this study.

PMID- 20050515
TI  - A qualitative analysis of patient-reported symptoms of anemia.
AB  - The objective of this study was to understand how patients with chronic kidney
      disease (CKD) who are on dialysis experience anemia. Methods included the re
      analysis of interviews with patients with CKD on dialysis who became anemic.
      Transcripts were coded for symptoms or the impact of symptoms using ATLAS ti
      software. Patients indicated anemia was associated with decreased "energy" (79%),
      "tired" (76%), "shortness of breath" (72%), and "loss of strength"/"weakness"
      (66%). It was found that patients with CKD on dialysis indicated that anemia is
      associated with a symptom cluster indicating loss of energy. Anemia assessments
      should incorporate these words and concepts. This article provides an overview of
      the results of this study.

PMID- 20050516
TI  - Revisions in the end stage renal disease prospective payment system: implications
      for nephrology nurses.
AB  - A revised end stage renal disease prospective payment system that expands the
      bundle of services payed for under the capitated rate will be gradually phased in
      beginning January 1, 2011. This article provides an overview of some primary
      components of the new payment system that will affect nephrology nurses, with an
      emphasis on the need to continually focus on quality initiatives that will
      improve overall patient outcomes.

PMID- 20050517
TI  - Blood pressure monitoring at home in patients with CKD: a little education can go
      a long way.

PMID- 20050518
TI  - Implications of obesity and kidney transplantation.

PMID- 20050519
TI  - Certified Clinical Hemodialysis Technician (CCHT) examination: dispelling the
      myths.

PMID- 20050520
TI  - Beyond needle placement: the role of the nephrology nurse in arteriovenous
      fistula management.

PMID- 20050521
TI  - Anemia management: a story of sleuthing.
AB  - ESA therapy is commonly initiated when the Hgb is less than 11 g/dL. The shared
      hope and expectation as we partner with patients and their families in the plan
      of care is that the way to attain intended outcomes will be clear and involve no
      mystery. It can be surprising and challenging when those outcomes are not easily
      met. Mr. I achieved the targets for TSAS and ferritin levels, and both he and his
      significant other demonstrated knowledge about anemia and its ramifications and
      skill in the administration of the ESA. However, during the time he was enrolled
      in the CKD anemia management program, he did not achieve or maintain a Hgb
      between 11.0 and 12.0 g/dL. What are the lessons learned and implications for
      nephrology nurses? Be specific with patients about their medications. Ask about
      injectable and intravenous medications, radiotherapy, drugs that affect DNA
      synthesis (such as chemotherapeutic drugs), street drugs, herbal therapies, and
      vitamins. Be thorough when obtaining a medical and lifestyle history, especially
      as it relates to conditions that may affect erythropoiesis, for example, is the
      patient smoking? How much alcohol does he drink? Has he seen a Healthcare
      provider for any old or new problems recently? In addition, patients with CKD
      have many co-morbidities, which may include cancer. ESA therapy becomes much more
      complex in the patient with cancer and CKD, and therapy may necessitate a
      different approach and different Hgb targets. Finally, nurses must be diligent
      and methodical in the quest to uncover the reasons for hyporesponsiveness in the
      patient with CKD who has anemia.

PMID- 20050522
TI  - Fluoroquinolone antibacterials: a review on chemistry, microbiology and
      therapeutic prospects.
AB  - Fluoroquinolones are one of the most promising and vigorously pursued areas of
      contemporary antiinfective chemotherapy depicting broad spectrum and potent
      activity. They have a relatively simple molecular nucleus, which is amenable to
      many structural modifications. These agents have several favorable properties
      such as excellent bioavailability, good tissue penetrability and a relatively low
      incidence of adverse and toxic effects. They have been found effective in
      treatment of various infectious diseases. This paper is an attempt to review the
      therapeutic prospects of fluoroquinolone antibacterials with an updated account
      on their development and usage.

PMID- 20050523
TI  - Indirect spectrofluorimetric determination of mosapride citrate in pharmaceutical
      formulations.
AB  - New europium complexes of 3-oxo-1-hydroxy-quinoline-2-carboxylic acid amide
      derivatives (L1-L3), which are highly luminescent and do not require luminescence
      enhancers are reported. The luminescence intensity of the Eu-L1-3 complexes was
      enhanced by the addition of citrate ions in water solution. A sensitive
      luminescence enhancement system was developed for the determination of citrate
      ions on the base of Eu-9-fluoro-1-hydroxy-5-methyl-3-oxo-6,7-dihydro-3H,5H
      pyrido[3,2,1-ij]quinoline-2-carboxylic acid (2-piperazin-1-yl-ethyl)-amide (L1)
      complex. This effect was applied to the determination of the drug, which is not a
      lanthanide luminescence sensitizer. The Eu-L1- Cit complex with a components'
      ratio 1:1:2 was proposed to be used as the analytical form for the luminescence
      determination of drug - mosapride citrate. The calibration curve is linear in the
      range of 1.0-25.0 microg/mL of mosapride citrate (LOD is 0.35 microg/mL). This
      method was applied for the determination of mosapride citrate in dosage form -
      tablets "Mosid MT" - 2.5 mg.

PMID- 20050524
TI  - Development and validation of GC-FID method for the determination of ethanol
      residue in marjoram ointment.
AB  - Our study describes the procedure development and validation of the GC-FID method
      for the determination of ethanol content in marjoram ointment. At the validation
      procedure linearity ranged from 1 x 10(-4)% to 1 x 10(-1)%, limit of detection
      was 5 x 10(-5)%, relative standard deviation for precision RSD = 1.07%, relative
      standard deviation for intermediate precision RSD = 1.43% and good recoveries
      (average 97,47%) were obtained. It is suggested after the analysis of ethanol
      content in marjoram ointments from different producers that the method is
      intended for routine standardization assays of ethanol. From the data of
      validation criteria it is suggested that the method is suitable for the
      determination and for the quality identification of ethanol residue in
      pharmaceutical products.

PMID- 20050525
TI  - Polyphenols action against oxidative stress formation in endothelial cells.
AB  - The aim of this study was to investigate the influence of epigallocatechin-3
      gallate (EGCG), theaflavins (TFs) and black tea extract (BTE) on oxidative stress
      formation as well as on antioxidant system of human vein endothelial cells
      (HUVEC). HUVEC were incubated for 0,5 h with 100 mM tert-butyl hydroperoxide (t
      BHP) for oxidative stress formation. The influence of EGCG, TFs, and BTE on
      oxidative stress and antioxidant system parameters was investigated by the pre
      incubation for 2 h with 50 mg/mL of each compound. Half hour exposure to t-BHP
      caused statistically significant decrease in GSH-Px activity and in the content
      of GSH, vitamin A, vitamin E as well as tryptophan. Moreover, pretreatment of
      cells with t-BHP caused statistically significant increase in activities of Cu,Zn
      SOD, GSSG-R and in the level of MDA and dityrosine. Pretreated with t-BHP
      endothelial cells, subjected to EGCG, TFs and black tea extract, are partially
      protected against oxidative activity of t-BHP causing statistically significant
      increase in GSH-Px activity, GSH and tryptophan level and decrease in MDA and
      dityrosine level in comparison with HUVEC pretreated with t-BHP group. These
      results indicate the beneficial effect of tea polyphenolic compounds on HUVEC
      antioxidant abilities and, in consequence, their protective effect in cell
      components.

PMID- 20050526
TI  - Synthesis of triazolothiazolidinone derivatives of coumarin with antimicrobial
      activity.
AB  - A series of 2-(substituted phenyl)-3-[3-(2-oxo-2H-chromen-3-yl)-5-thioxo-1,5
      dihydro-4H-1,2,4-triazol-4-yl]-1,3-thiazolidin-4-ones, 8a-n, were synthesized and
      evaluated for their antimicrobial activity. The structures of the compounds were
      confirmed on the basis of their elemental analysis and spectral data. Compounds
      8k, 81 and 8m showed significant inhibition against S. aureus, compound 8m showed
      significant inhibition against E. coli and compounds 8b, 8e, 8i, 8j, 8k, 81 and
      8m showed significant inhibition against C. albicans.

PMID- 20050527
TI  - Analogues of distamycin--synthesis and biological evaluation of new aromatic
      oligopeptides, potential anticancer agents.
AB  - Six new aromatic oligopeptides were synthesized and evaluated for their activity
      in the standard cell line of the mammalian tumor MCF-7 as well as in a cell-free
      system employing the topoisomerase I/II inhibition assay.

PMID- 20050528
TI  - Synthesis, physicochemical and anticonvulsant properties of new N-[(4
      arylpiperazin-1-yl)alkyl]-3-phenyl- and 3-(3-methyl-phenyl)-pyrrolidine-2,5
      diones.
AB  - The series of N-[(4-arylpiperazin-1-yl)-alkyl]-3-phenyl- and 3-(3-methylphenyl)
      pyrrolidine-2,5-diones [VIII-XXV] were synthesized and evaluated for
      anticonvulsant and neurotoxic properties. Initial anticonvulsant screening was
      performed in mice, using intraperitoneal (ip) maximal electroshock-induced
      seizures (MES) and subcutaneous pentylenetetrazole-induced (scPTZ) seizure
      threshold tests. The neurotoxicity was determined applying the rotorod screen.
      Compounds VIII-XXV revealed protection only in the electrically induced seizures
      or were inactive. The most active were Mannich bases of 3-(3-methylphenyl)
      pyrrolidine-2,5-dione with electron-withdrawing substituents at position-3 of 4
      arylpiperazine fragment [XVII, XVIII], as well as compounds with ethylene or
      propylene spacer between imide and 4-arylpiperazine nitrogen atoms [XX-XXII,
      XXV]. All these compounds showed anti-MES protection in mice at doses of 100
      mg/kg. Additionally, when given orally, compound XVIII was also active in rats
      MES screen at a dose of 30 mg/kg.

PMID- 20050529
TI  - Synthesis and pharmacological evaluation of new 1-[3-(4-phenylpiperazin-1-yl)
      propyl]- and 1-[3-(4-phenylpiperidine)-propyl]- 3-aryl-3-alkyl-pyrrolidin-2-one
      derivatives with antiarrhythmic and antihypertensive activity.
AB  - A series of novel phenylpiperazine and phenylpiperidine derivatives bearing a 3,3
      disubstituted pyrrolidin-2-one fragment were synthesized and evaluated for their
      binding affinity for alpha1-adrenoceptors (ARs) and for their antiarrhythmic and
      antihypertensive activities. The highest affinity for alpha1-ARs was displayed by
      1-[2-hydroxy-3-(4-phenylpiperazin-l-yl)-propyl]-3-phenyl-3-n-propyl-pyrrolidin-2
      one (10 a), which binds with pK(i) = 6.43. Among the compounds tested, 1-(2
      hydroxy-3-(4-phenylpiperidin-1-yl)-propylpyrrolidin-2-one (5) was the most active
      in the prophylactic antiarrhythmic activity in adrenaline induced arrhythmia in
      anesthetized rats. Its ED50 value was 4.9 mg/kg intravenously (i.v.). Some of the
      compounds tested significantly decreased the systolic and diastolic pressure in
      normotensive anesthetized rats at a dose of 5.0 mg/kg i.v. and their hypotensive
      effects lasted for longer than an hour.

PMID- 20050530
TI  - Synthesis and anticonvulsant activity of new spirosuccinimides differently
      substituted at the imide nitrogen atom.
AB  - In the present study the series of spirosuccinimides with the aromatic ring at
      the imide nitrogen atom was synthesized. All the compounds were tested for their
      anticonvulsant activity in the maximal electroshock (MES) and subcutaneous
      pentylenetetrazole (scPTZ) screens. The neurotoxic properties were determined
      applying the rotorod test (TOX). The most active were N-(2-methoxyphenyl)- [V]
      and N-(4-chlorophenyl-amino)-2-azaspiro[4.5]decane-1,3-dione [XI] that inhibited
      seizures at a dose of 100 mg/kg in the scPTZ and MES tests, respectively. The
      other derivatives, namely N-(3-methoxyphenyl)- [VI], N-(1-phenylethyl)- [VIII], N
      (diphenylmethyl)- [IX], N-(6-aminopyridin-2-yl)- [XII] 2-azaspiro[4.5]decane-1,3
      diones, and the compounds with the methyl group at position-3 [XIV, XVII] or at
      position-4 [XVIII] of the cyclohexane ring showed anti-MES and/or anti-scPTZ
      protections at doses of 300 mg/kg. The results obtained revealed that
      anticonvulsant activity depended on the substitution mode of the aromatic ring as
      well as the kind of spacer between imide nitrogen atom and aromatic system.

PMID- 20050531
TI  - 2-[(Arylmethoxy)imino]imidazolidines with potential biological activities.
AB  - A series of 2-[(arylmethoxy)imino]imidazolidines was synthesized by reacting 2
      chloro-4,5-dihydroimidazole with corresponding O-arylmethylhydroxylamines and
      evaluated for their alpha-, alpha2-adrenergic and imidazoline I1, I2 receptor
      binding affinities. The most potent 2-[(naphthalen-1
      ylmethoxy)imino]imidazolidine showed a high selectivity and good affinity for the
      [3H]prazosin-labeled alpha1-adrenoceptors (K(i) = 107 nM). Representative
      compounds of this series were also tested in vivo for possible circulatory
      effects in rats after intravenous administration.

PMID- 20050532
TI  - Analysis of the antimicrobial activity of propolis and lysozyme in semisolid
      emulsion systems.
AB  - Propolis as an active natural substance is attractive due to its antimicrobial
      and antimycotic properties. Lysozyme was added to semisolid dermatological
      preparations as a complementary substance capable of potentiating their
      antimicrobial and antimycotic effect; this substance has been used for several
      decades as a preservative in food industry. The aim of this study was to model a
      semisolid emulsion system (o/w) for cutaneous use with moisturizing and
      antimicrobial properties, where the active substances would be propolis and/or
      lysozyme. The microbiological examination was performed under aseptic conditions.
      The microbiological examination was aimed at determining the antimicrobial
      efficacy of the studied preparation in the solid growth media using the wells
      technique. The results of the antimicrobial assay showed that the effectiveness
      of propolis against the growth of S. aureus was intensified by the lysozyme
      introduced into the emulsion systems. In addition to that, the results of
      examinations showed that the active substance propolis in emulsion systems more
      efficiently inhibited spore bacteria (Bacillus cereus) than lysozyme did, yet
      lysozyme had a more pronounced antimycotic (against Candida albicans) effect,
      compared to propolis. All studied cream samples inhibited the growth of Gram
      negative microorganisms (Escherichia coli). The results of this study suggest
      that the application of propolis and lysozyme as the active substances may
      increase the antimycotic and antibacterial effect of the studied preparations.

PMID- 20050533
TI  - Spermatotoxic effect of ochratoxin and its amelioration by Emblica officinalis
      aqueous extract.
AB  - The present study was carried out to evaluate the spermatotoxic effect of
      ochratoxin and it's amelioration by Emblica officinalis aqueous extract. When
      male albino mice were treated with ochratoxin (50 and 100 microg/0.2 mL of olive
      oil/animal/day for 45 days, orally) alterations in various reproductive
      parameters were observed (sperm count, sperm motility, sperm viability and
      fertility rate), when further treated with the aqueous extract of Emblica
      officinalis (2 mg/animal/day for 45 days) amelioration was noted in ochratoxin
      induced spermatotoxic effect. Oral administration of ochratoxin for 45 days
      caused, as compared to vehicle control (Group 2), dose-dependent significant (p <
      0.05) reduction in cauda epididymal sperm count, sperm motility, sperm viability
      and fertility rate (Groups 4, 5). Oral administration of aqueous extract of
      Emblica officinalis alone did not cause any significant changes in above
      mentioned parameters (Group 3). However, Emblica officinalis aqueous extract
      along with ochratoxin treatment caused significant recovery in all the sperm
      parameters as well as in fertility rate (Groups 6, 7) in comparison with
      ochratoxin alone treated animals (Groups 4, 5). Amelioration was higher in high
      dose ochratoxin plus extract treated animals than that of respective low dose.
      When normal human sperm cell suspension was treated with ochratoxin (in vitro),
      various morphological alterations were observed. These were mitigated further,
      when treated with aqueous extract of Emblica officinalis.

PMID- 20050534
TI  - Stability studies of expired tablets of metoprolol tartrate and propranolol
      hydrochloride. Part 1. Content determination.
AB  - In recent years the growing interest in drug stability problem has been observed.
      The stability of pharmaceutical products seems to play an important role from the
      economical point of view. However, there are not many studies that reported about
      the stability of drugs past their expiration dates. The objective of the current
      study was to determine tablet content of expired tablets and tablets with expiry
      date has not been exceeded. The analyzed tablets contained metoprolol tartrate
      (50 mg) and propranolol hydrochloride (10 mg), respectively. Content
      determination was performed using HPLC method with UV detection. The proposed
      method was validated with regard to linearity, sensitivity, intermediate accuracy
      and precision. No discrepancies between the results of determination and the
      declared values range for all the analyzed tablets were observed. The results of
      performed study might suggest that storage of analyzed batches of tablets over
      time period exceeding the expiry date given by the manufacturer did not influence
      their contents.

PMID- 20050535
TI  - Stability studies of expired tablets of metoprolol tartrate and propranolol
      hydrochloride. Part 2. Dissolution study.
AB  - The objective of the current study was to determine tablet content and perform
      dissolution test of expired tablets and tablets which expiry date has not
      exceeded. The analyzed tablets contained metoprolol tartrate (50 mg) and
      propranolol hydrochloride (10 mg), respectively. Content determination was
      performed using spectrophotometric method with UV detection; the percent of
      dissolved substance from tablets during dissolution test was performed using
      spectrophotometric method, as well. The proposed methods were validated with
      regard to linearity, sensitivity, and intermediate accuracy and precision. No
      discrepancies between the results of determination and the declared values range
      for all the analyzed tablets were observed. The results of performed study might
      suggest that the storage of analyzed batches of tablets over time period
      exceeding the expiry date given by the manufacturer did not influence their
      contents.

PMID- 20050536
TI  - Solubility of ocular therapeutic agents in self-emulsifying oils. I. Self
      emulsifying oils for ocular drug delivery: solubility of indomethacin, aciclovir
      and hydrocortisone.
AB  - Self-emulsifying drug delivery systems (SEDDS) were prepared by dissolving
      Cremophor EL, Tween 20, Tween 80 and Span 80 (1% or 5%) in oils (Miglyol 812 or
      castor oil). Solubilities of three ophthalmic drugs, namely aciclovir,
      hydrocortisone and indomethacin were determined in these systems. In addition,
      the effect of a small amount of water (0.5% and 2%) on solubilization properties
      of the systems was estimated. Of the three substances, indomethacin showed the
      best solubility in Miglyol while aciclovir was practically insoluble in this oil.
      The surfactants usually increased drug solubility in the oily phase. Only Tween
      20 was found to decrease the solubility of aciclovir and hydrocortisone in
      Miglyol. Addition of a small amount of water to the oil/surfactant system
      increased solubility of hydrocortisone, but not of indomethacin. The results of
      the current study may be utilized to design a suitable composition of SEDDS and
      allow continuation of research on this type of drug carriers.

PMID- 20050537
TI  - Influence of oxcarbazepine on the antinociceptive action of morphine and
      metamizole in mice.
AB  - Numerous methods of management applied in order to obtain higher therapeutic
      efficacy of drugs with minimum adverse effects include taking advantage of
      interactions taking place between individual agents. Analgesics are combined with
      drugs belonging to other therapeutic groups, including, more and more frequently,
      antiepileptic agents. The influence of oxcarbazepine (10 mg/kg) on the
      antinociceptive effect of morphine (10 mg/kg) and metamizole (500 mg/kg) was
      investigated in mice using the hot-plate and tail-flick tests. All drugs were
      injected intraperitoneally (i.p.). Oxcarbazepine was administered 30 min prior to
      the injection of analgesic drugs. The reactions to noxious stimuli were measured
      30, 60 and 90 min after the administration of an analgesic. The study was further
      conducted for 10 days with repeated drug doses. Single administration of
      oxcarbazepine enhanced the antinociceptive effect of a single dose of morphine,
      and 10-day administration led to a decrease of morphine tolerance in the hot
      plate test. Oxcarbazepine administered in a single dose did not affect
      significantly the antinociceptive effect of metamizole in either of the tests.
      Multiple administration of oxcarbazepine enhanced the antinociceptive effect of
      metamizole in the hot-plate test. Oxcarbazepine alone, administered in a single
      and repeated doses, demonstrated an antinociceptive effect, but only for the hot
      plate test, which indicates involvement of supraspinal structures in
      antinociception.

PMID- 20050538
TI  - Ultrasound enhancement of the reduction of the Basic Green dye in wastewater by
      cast iron.

PMID- 20050539
TI  - Effect of chlorpyrifos on soil microbial populations and enzyme activities.

PMID- 20050540
TI  - Effects of thermally pretreated temperature on bio-hydrogen production from
      sewage sludge.
AB  - Hydrogen can be obtained by anaerobic fermentation of sewage sludge. Therefore,
      in this paper the effects of thermally pretreated temperatures on hydrogen
      production from sewage sludge were investigated under different pre-treatment
      conditions. In the thermal pretreatment, some microbial matters of sludge were
      converted into soluble matters from insoluble ones. As a result, the suspended
      solid (SS) and volatile suspended solid (VSS) of sludge decreased and the
      concentration of soluble COD (SCOD) increased, including soluble carbohydrates
      and proteins. The experimental results showed that all of those pretreated sludge
      could produce hydrogen by anaerobic fermentation and the hydrogen yields under
      the temperatures of 121 degrees C and 50 degrees C were 12.23 ml/g VS (most) and
      1.17 ml/g VS (least), respectively. It illuminated that the hydrogen yield of
      sludge was affected by the thermally pretreated temperatures. Additionally, the
      endurance of high hydrogen yield depended on the translation of microbial matters
      and inhibition of methanogens in the sludge. The temperatures of 100 degrees C
      and 121 degrees C (treated time, 30 min) could kill or inhibit completely the
      methanogens while the others could not. To produce hydrogen and save energy, 100
      degrees C was chosen as the optimal temperature for thermal pretrcatment. The
      composition changes in liquid phase in the fermentation process were also
      discussed. The SCOD of sludge increased, which was affected by the pretreatment
      temperature. The production of volatile fatty acids in the anaerobic fermentation
      increased with the pretreatment temperature.

PMID- 20050541
TI  - Decomposition kinetics of dimethyl methylphospate (chemical agent simulant) by
      supercritical water oxidation.
AB  - Supercritical water oxidation (SCWO) has been drawing much attention due to
      effectively destroy a large variety of high-risk wastes resulting from munitions
      demilitarization and complex industrial chemical. An important design
      consideration in the development of supercritical water oxidation is the
      information of decomposition rate. In this paper, the decomposition rate of
      dimethyl methylphosphonate (DMMP), which is similar to the nerve agent VX and GB
      (Sarin) in its structure, was investigated under SCWO conditions. The experiments
      were performed in an isothermal tubular reactor with a H2O2 as an oxidant. The
      reaction temperatures were ranged from 398 to 633 degrees C at a fixed pressure
      of 24 MPa. The conversion of DMMP was monitored by analyzing total organic carbon
      (TOC) on the liquid effluent samples. It is found that the oxidative
      decomposition of DMMP proceeded rapidly and a high TOC decomposition up to 99.99%
      was obtained within 11 s at 555 degrees C. On the basis of data derived from
      experiments, a global kinetic equation for the decomposition of DMMP was
      developed. The model predictions agreed well with the experimental data.

PMID- 20050542
TI  - Dyes wastewater treatment by reduction-oxidation process in an electrochemical
      reactor packed with natural manganese mineral.
AB  - A novel technology which combined electrochemical process catalyzed by manganese
      mineral with electro-assisted coagulation process was proposed in this study. The
      mineralization of organic pollutant from simulated dye wastewater containing an
      azo dye Acid Red B (ARB) was experimentally investigated using this method. It
      was found that the manganese mineral could catalyze the electrochemical process
      dramatically. The TOC removal percentage of electrochemical treatment catalyzed
      by manganese mineral was 43.6% while the TOC removal percentage of the process
      using the manganese mineral alone and using the electrolysis alone were 9.3% and
      20.8%, respectively. Moreover, it was found that combined electroxidation with
      electro-assisted coagulation process could more effectively eliminate ARB. After
      a period of 180 min electrooxidation and 300 min electroreduction, almost 66.9%
      of TOC was removed, and the dissolved Mn2+ could be effectivly removed. The
      effects of the order of oxidation and reduction, the proper ratio
      electrooxidation/reduction time, and current density on the removal efficiency
      were investigated in detail. In addition, a proposed mechanism of manganese
      mineral-catalyzed electrooxidation-reduction process was discussed in this paper.

PMID- 20050543
TI  - Adsorption removal of thiocyanate from aqueous solution by calcined hydrotalcite.
AB  - A hydrotalcite with Mg/Al molar ratio 2 was prepared by co-precipitation method
      and was characterized by XRD, TG/DTA, Zeta potential and BET surface area. The
      hydrotalcite was calcined at 500 degrees C, with the dehydration from interlayer,
      the dehydroxilation from the brucite-like layer and the decomposition of
      carbonate successively, transformed into the mixed oxide type. The removal of
      thiocyanate from aqueous solution by using the original hydrotalcite and calcined
      hydrotalcite (HTC-500) was investigated. The results showed that the thiocyanate
      adsorption capacity of calcined hydrotalcite was much higher than that of the
      original form. Calcined hydrotalcite was particularly effective at removing
      thiocyanate, and that the effective range of pH for the thiocyanate removal are
      between 5.5-10.0. The experimental data of thiocyanate removal fit nicely with
      Langmuir isotherm, and the saturated adsorption uptake was 96.2 mg SCN-/g HTC
      500. The adsorption of thiocyanate by calcined hydrotalcite follows first-order
      kinetics. And the intercalation to the structure recovery for calcined
      hydrotalcite. But the presence of additional anions could affect the adsorption
      behavior of thiocyanate.

PMID- 20050544
TI  - Advanced treatment of oil recovery wastewater from polymer flooding by UV/H2O2/O3
      and fine filtration.
AB  - In order to purify oil recovery wastewater from polymer flooding (ORWPF) in
      tertiary oil recovery in oil fields, advanced treatment of UV/H2O2/O3 and fine
      filtration were investigated. The experimental results showed that polyacrylamide
      and oil remaining in ORWPF after the conventional treatment process could be
      effectively removed by UV/H2O2/O3 process. Fine filtration gave a high
      performance in eliminating suspended solids. The treated ORWPF can meet the
      quality requirement of the wastewater-bearing polymer injection in oilfield and
      be safely re-injected into oil reservoirs for oil recovery.

PMID- 20050545
TI  - Mechanism study of electrochemical oxidation in the terylene diaphragm cell.
AB  - By using a self-made carbon/polytetrafluoroethylene (C/PTFE) O2-fed as cathode
      and Ti/IrO2/RuO2 as anode, the effects of electrochemical oxidation of phenol and
      the coal-gas wastewater containing phenol were studied. The terylene diaphragm
      which kept pH >12 in cathodic compartment and pH < 1 in the anodic compartment
      was selected in the experiment in comparison with the other types of diaphragm.
      Furthermore, hydroxyl radical (HO*) was determined in the cathodic compartment of
      the diaphragm cell by electron spin resonance spectrum (ESR) and the fluorescence
      spectra. Compared with pH, the accumulated H2O2 and the COD removal of the no
      diaphragm cell, the mechanism of electrochemical oxidation in the terylene
      diaphragm cell was supposed. The degradation of phenol was supposed to be
      cooperative oxidation by direct or indirect electrochemical oxidation at the
      anode and H2O2, HO* produced by oxygen reduction at the cathode. The
      mineralization of phenol in the diaphragm cell was better than that in the no
      diaphragm cell. When the coal-gas wastewater was treated by the electrolysis
      system with terylene diaphragm, the average removal efficiency of the volatile
      phenol and COD were 100% and 79.6%, respectively.

PMID- 20050546
TI  - Iron stability in drinking water distribution systems in a city of China.
AB  - A field study on the estimation and analysis of iron stability in drinking water
      distribution system was carried out in a city of China. The stability of iron ion
      was estimated by pC-pH figure. It was found that iron ion was unstable, with a
      high Fe(OH)3 precipitation tendency and obvious increase in turbidity. The outer
      layer of the corrosion scale was compact, while the inner core was porous. The
      main composition of the scale was iron, and the possible compound constitutes of
      the outer scale were a-FeOOH, gamma-FeOOH, alpha-Fe2O3, gamma-Fe2O3, FeCl3, while
      the inner were Fe3O4, FeCl2, FeCO3. According to the characteristics of the
      corrosion scale, it was thought that the main reason for iron instability was
      iron release from corrosion scale. Many factors such as pipe materials, dissolved
      oxygen and chlorine residual affect iron release. Generally, higher iron release
      occurred with lower dissolved oxygen or chlorine residual concentration, while
      lower iron release occurred with higher dissolved oxygen or chlorine residual
      concentration. The reason was considered that the passivated out layer of scale
      of ferric oxide was broken down by reductive reaction in a condition of low
      oxidants concentration, which would result more rapid corrosion of the pipe and
      red water phenomenon.

PMID- 20050547
TI  - Comparative study on the removal technologies of 2-methylisoborneol (MIB) in
      drinking water.
AB  - Removal of 2-methylisoborneol (MIB) in drinking water by ozone, powdered
      activated carbon (PAC), potassium permanganate and potassium ferrate was
      investigated. The adsorption kinetics of MIB by both wood-based and coat-based
      PACs show that main removal of MIB occurs within contact time of 1 h. Compared
      with the wood-based PAC, the coat-based PAC evidently improved the removal
      efficiency of MIB. The removal percentage of trace MIB at any given time for a
      particular carbon dosage was irrelative to the initial concentration of MIB. A
      series of experiments were performed to determine the effect of pH on the
      ozonation of MIB. The results show that pH has a significant effect on the
      ozonation of MIB. It is conclusive that potassium permanganate and potassium
      ferrate are ineffective in removing the MIB in drinking water.

PMID- 20050548
TI  - Simultaneous phosphorus and nitrogen removal in a continuous-flow two-sludge
      system.
AB  - The ability of simultaneous biological phosphorus and nitrogen removal was
      investigated in a lab-scale continuous-flow two-sludge system. Alternating
      anaerobic and anoxic conditions were combined with contact oxidation stage for
      treating raw municipal wastewater. Long-term experiments showed that the
      contradiction of competing for the organic substrate between denitrifying
      bacteria and PAOs (phosphorus accumulating organisms) in traditional phosphorus
      and nitrogen removal system has been resolved. The system can adapt to low
      influent COD/TN ratio (C/N). Furthermore the SRT (sludge retention time) of
      nitrifying sludge and denitrifying phosphorus removal sludge can be controlled at
      optimal conditions respectively. The removal efficiency of COD, TP, TN, and NH4-N
      was 81.78%, 92.51%,75.75%, and 84.47% respectively. It was also found that the
      appropriate influent C/N should be controlled at the range of 3.8-6, while the
      optimal C/N to the system ranged between 4-5, and the BFR (bypass sludge flow
      rate) should be controlled at 0.35 around.

PMID- 20050549
TI  - Control strategy of shortcut nitrification.
AB  - Shortcut nitrification for ammonium-rich wastewater is energy-saving and cost
      effective procedure that has become one of the hotspots in the field of
      biological denitrogenation. An orthogonal experiment was performed to study the
      combined effects of operational parameters on the performance of internal-loop
      airlift bioreactor for shortcut nitrification. The optimum operational parameters
      for the shortcut nitrification were found as temperature 35 degrees C, pH 8.0,
      dissolved oxygen concentration 1.0 mg/L, ammonium concentration 4 mmol/L and HRT
      16 h, which have different influence on the performance of shortcut nitrification
      reactor. The pH, temperature and dissolved oxygen concentration have significant
      bearing on the process. The results showed that the shortcut nitrification
      reactor could be successfully started up within 42 d, and the reactor performance
      is steady with minimum NO2-/NOx- of 85.2%, maximum 93.4% and average value of
      91.4% in effluent. Based on the analysis of experimental data, a new control
      strategy named "priority + combination" for shortcut nitrification was suggested.
      Through this strategy, the startup and operation of shortcut nitrification for
      ammonium-rich sludge digester liquids were optimized. The control strategy works
      well to keep the reactor operation in steady state and in achieving high
      efficiency for shortcut nitrification.

PMID- 20050550
TI  - Simulation and control strategy for the variational influent of WWTP.
AB  - With the development of activated sludge model, the simulation software for the
      design and operation of wastewater treatment plant (WWTP) was produced and has
      been widely used. The dynamic change of the quality and flow of influent are
      major factors causing the unstable operation of wastewater treatment process. As
      a basic model, ASM1 model was used for the simulation of activated sludge
      process, and double exponential model was selected for the simulation of
      secondary sedimentation tank. The influences of influent change to the aeration
      tank and secondary sedimentation tank were investigated, and the relationship
      among influent change, the quality of effluent and the level of sludge blanket in
      secondary sedimentation tank was established. On the basis of the simulation
      results, the operation of the WWTP could be adjusted under the dynamic change of
      the influent. Furthermore, the controlling strategy combined the feed-forward on
      the influent flow and the feedback on the level of sludge blanket in the
      secondary sedimentation tank was studied.

PMID- 20050551
TI  - Observation of atmospheric nitrous acid with DOAS in Beijing, China.
AB  - Measurements of nitrous acid (HONO) and nitrogen dioxide (NO2) in Beijing City
      have been performed by means of a developed differential optical absorption
      spectroscopy (DOAS) system based on photodiode array (PDA), during the autumn of
      2004. HONO and NO2 were simultaneously identified by their characteristic
      absorption bands in the spectral region between 337 nm and 372 nm with high
      sensibility and time resolution. The concentrations of HONO exhibit obviously
      diurnal variation with a nocturnal maximum and a daytime minimum. The highest
      HONO value up to 11.8 microg/m3 was observed during the night of 2/3 September.
      Possible sources of the observed HONO were discussed. Good correlation to NO2
      indicates that NO2 is a main source component. The measurement also shows direct
      emission of HONO is an important source in strongly polluted urban area.

PMID- 20050552
TI  - Morphology of metal nanoparticles photodeposited on TiO2/silical gel and
      photothermal activity for destruction of ethylene.
AB  - The morphology of supported metal nanoparticles on TiO2/silical gel (TSO) and
      photothermal synergism were investigated for destruction of ethylene. During
      photocatalytic deposition of metal nanopartilces, the effects of pH and light
      intensity on the morphology of coated platinum, palladium, gold on TiO2/silical
      gel were studied. Moreover, these catalysts were characterized by TEM, UV-Vis
      DRS. The pH of preparing solution have strong influence on dispersion, size and
      sites ofPt, Pd and Au on TSO, which were controlled by the electrostatic binding
      of HPtCl6-, AuCl4- and TiOH2+, Pd2+ and TiO- respectively. Platinum, gold and
      palladium nanoparticles were uniformly highly dispersed on the titanol sites not
      silanol of TiO2 /silical gel under pH = 2, pH = 9.9 respectively. For the
      photodegradation of ethylene, they show higher photothermal efficiency than those
      prepared with other pH conditions under UV illumination in a non-circulating
      photoreactor. The optimum weight loadings of Pt, Au, and Pd were 0.25 wt%, 0.5
      wt%, 1 wt%, respectively. The synergistic effect enhanced ethylene removal and
      CO2 production. These results verify that the best photothermal synergistic
      effect depends on the dispersion, size of noble metal nano-particles. FTIR
      analyses of the used Pt-, Pd-TSO catalysts indicated that no significant by
      products were accumulated on the surface of the catalysts, leading to them longer
      lifetime.

PMID- 20050553
TI  - Decomposition of CCl4 and CHCl3 on gliding are plasma.
AB  - Decomposition of chlorinated hydrocarbons, CCl4 and CHCl3, in gliding plasma was
      examined. The effects of initial concentrations, total gas flow rates, and power
      consumption have been investigated. The conversion result was relatively high. It
      reached 80% for CCl4 and 97% for CHCl3. Using atmospheric air as the carrier gas,
      the plasma reaction occurred at exothermic reaction and the main products were
      CO2, CO, and Cl2. Transformation into CCl4 was also detected for CHCl3
      decomposition reaction. The conversion of CCl4 and CHCl3 were increased with the
      increasing applied frequency and decreasing total gas flow rate.

PMID- 20050554
TI  - Mineralogical characterization of airborne individual particulates in Beijing
      PM10.
AB  - This work mainly focuses on the mineralogical study of particulate matter (PM10)
      in Beijing. Samples were collected on polycarbonate filter from April, 2002 to
      March, 2003 in Beijing urban area. Scanning electronic microscopy coupled with
      energy dispersive X-ray (SEM/EDX) was used to investigate individual mineral
      particles in Beijing PM10. 1454 individual mineral particulates from 48 samples
      were analysed by SEM/EDX. The results revealed that mineral particulates were
      complex and heterogeneous. 38 kinds of minerals in PM10 were identified. The clay
      minerals, of annual average percentage of 30.1%, were the main composition among
      the identified minerals, and illite/smectite was the main composition in clay
      minerals, reaching up to 35%. Annual average percentage of quartz, calcite,
      compound particulates, carbonates were 13.5%, 10.9%, 11.95%, 10.31%,
      respectively. Annual average percentage less than 10% were gypsum, feldspar,
      dolomite, and so on. Fluorite, apatite, halite, barite and chloridize zinc
      (ZnCl2) were firstly identified in Beijing PM10. Sulfurization was found on
      surface of mineral particles, suggested extensive atmospheric reaction in air
      during summer.

PMID- 20050555
TI  - Arsenate and phosphate interaction in Saccharomyces cerevisiae.
AB  - In the present study, arsenate (As(V)) and phosphate (P(V)) interactions were
      investigated in growth, uptake and RNA content in yeast (Saccharomyces
      cerevisiae). Yeast grew slowly with As(V) concentrations increasing in the
      medium. However, the maximal population density was almost the same among
      different As(V) treatments. It was in the late log phase that yeast growth was
      augmented by low As(V), which was maybe due to the fact that methionine
      metabolism was stressed by vitamin B6 deprivation, so As(V) treatments did not
      affect maximal population density. However, with P (V) concentrations increasing,
      the maximal population density increased. Therefore, the maximal population
      density was determined by P (V) concentrations in the medium but not by As (V)
      concentrations in the medium. Ycfl p(a tonoplast transpor) transports As(GS)3
      into the vacuole, but arsenic(As) remaining in the thalli was 1.27% with As(V)
      exposure for 60 h, from which it can be speculated that the percentage of As
      transported into vacuole should be lower than 1.27%. However, the percentage of
      As pumped out of cell was 71.49% with As (V) exposure for 68 h. Although two
      pathways (extrusion and sequestration) were involved in As detoxification in
      yeast, the extrusion pathway played a major role in As detoxification. RNA
      content was the highest in the early-log phase and was reduced by As(V).

PMID- 20050556
TI  - Effect of dissolved organic matter on the toxicity of chlorotoluron to Triticum
      aestivum.
AB  - Response of two wheat cultivars (Triticum aestivum cv. YM 158 and NM 9) to the
      herbicide chlorotoluron and the effect of two forms of dissolved organic matter
      on the chlorotoluron toxicity to the plants were characterized. Treatment with
      chlorotoluron at 10-50 microg/ml inhibited the seed germination and a dose
      response was observed. The inhibition of seed germination was correlated to the
      depression of alpha-amylase activities. To identify whether chlorotoluron induced
      oxidative damage to wheat plants, the malondlaldehyde (MDA) content and
      electrolyte leakage were measured. Results showed that both MDA content and
      electrolyte leakage in the chlorotoluron-treated roots significantly increased.
      Activities of several key enzymes were measured that operate in citric acid cycle
      and carbohydrate metabolic pathway. Inhibited activities of citrate synthase and
      NADP-isocitrate dehydrogenase were observed in the chlorotoluron-treated roots as
      compared to control plants. We also examined malate dehydrogenase and
      phosphoenolpyruvate carboxylase in wheat roots exposed to 30 gg/ml chlorotoluron.
      However, none of the enzymes showed significant changes in activities.
      Application of 160 microg/ml dissolved organic matter (DOM) extracted from non
      treated sludge (NTS) and heat-expanded sludge (HES) in the medium with 30
      microg/ml chlorotoluron induced an additive inhibition of seed germination and
      plant growth. The inhibition of growth due to the DOM treatment was associated
      with the depression of activities of alpha-amylase, citrate synthase and NADP
      isocitrate dehydrogenase, as well as the increase in malondlaldehyde content and
      electrolyte leakage. These results suggested that the presence of DOM might
      enhance the uptake and accumulation of chlorotoluron, and thus resulted in
      greater toxicity in wheat plants. The two forms of DOM exhibited differences in
      regulation of chlorotoluron toxicity to the wheat plants. Treatments with DOM-NTS
      induced greater toxicity to plants as compared to those with DOM-HES. In addition
      to DOM affecting chlorotoluron-induced toxicity to wheat plants, the cultivars
      could have also contributed to differences. Generally, NM-9 showed a higher
      sensitivity to chlorotoluron than YM 158 either in the absence or in the presence
      of DOM.

PMID- 20050557
TI  - Influences of petroleum on accumulation of copper and cadmium in the polychaete
      Nereis diversicolor.
AB  - Using the exposure simulation experiment, the action of petroleum affecting the
      accumulation of the trace metals including copper (Cu) and cadmium (Cd) in
      littoral polychaete Nereis diversicolor collected from the Shuangtaizi Estuary in
      Liaoning Province, China was examined. The results showed that there was a
      markedly non-linear relationship between the accumulation of Cu in worms and the
      experimental concentration of Cu in exposure solutions when the concentration of
      petroleum remained at 0, 100, and 220 microl/L, respectively. However,
      significantly non-linear relationship for worms exposed to Cd was observed only
      when the concentration of added petroleum was 0 and 220 microl/L. The
      accumulation of Cu in worms did not differ significantly among the three
      different levels of petroleum concentrations combined with various concentrations
      of Cu. So was the accumulation of Cd in worms (p > 0.05). However, the addition
      of petroleum in exposure solutions brought about an increase in the accumulation
      of Cu in Nereis diversicolor, in comparison with single Cu pollution. On the
      other hand, when the concentration of added petroleum remained at 100 microl/L,
      the accumulation of Cd in worms was lower than that in worms exposed to various
      concentrations of only cadmium. However, the worms exposed to Cd and petroleum
      220 microl/L did not show obvious and identical increase in the accumulation of
      Cd, compared with single Cd exposure. The accumulation of both Cu and Cd in worms
      did not increase significantly with the increases in concentrations of Cu or Cd
      in exposure solutions combined with petroleum (0, 100, and 220 microl/L) under
      the experimental conditions. Although Nereis diversicolor is exposed to very high
      Cu and Cd in exposure solutions, accumulation and detoxification mechanisms are
      sufficient to cope with the extra metal influx in order to survive.

PMID- 20050558
TI  - Reducing non-point source pollution with enhancing infiltration.
AB  - The rainfall system was set up on a slope land, which was used with some
      materials to enhance soil infiltration. The results showed that it was effective
      to enhance the infiltration of rainwater in soil and reduce the pollutants of
      surface runoff. After the soil meliorated by the lignin polymer and zeolite,
      runoff was delayed about 10 min and reduced by 44.40%-50.00%, synchronously, the
      pollutant loads, such as total suspended solids (TSS), chemical oxygen demand by
      ditromate (COD(Cr)), total nitroger (TN) and total phosphorus (TP), were reduced
      on averages by 44.58%, 37.80%, 51.62% and 44.11%, respectively. It is an
      available technique to control the pollution of non-point source from sources.

PMID- 20050559
TI  - Variations among rice cultivars on root oxidation and Cd uptake.
AB  - In order to understand the mechanisms on the variation between rice cultivars in
      Cd uptake and accumulation, two pot soil experiments were conducted with typical
      rice cultivars that varied greatly in soil Cd uptake. The experiments with six
      rice cultivars showed that the root oxidation abilities of rice differed with
      rice cultivars and also with types of the cultivars, the cultivars with indica
      consanguinity were significantly higher than the cultivars with japonica
      consanguinity. Root oxidation abilities of the rice cultivars correlated
      positively and significantly (P < 0.01) with their Cd concentrations and Cd
      quantity accumulations in rice plants. The experiments with two rice cultivars
      showed that significant differences also existed between the two cultivars in pot
      soil redox potentials, which of Shan you 63 (higher soil Cd accumulator) were
      significantly higher than that of Wu yun jing 7 (lower soil Cd accumulator) under
      different soil Cd levels, but the degrees of the differences varied with soil Cd
      levels. The differences were larger under soil Cd treatments than the control.
      The results indicate that root oxidation ability, especially in Cd contaminated
      soil, is one of the main mechanisms which dominate Cd uptake and accumulation by
      rice plant.

PMID- 20050560
TI  - Effects of cerium on growth and physiological mechanism in plants under enhanced
      ultraviolet-B radiation.
AB  - Effect of cerium (Ce3+) on the growth, photosynthesis and antioxidant enzyme
      system in rape seedlings (Brassica juncea L.) exposed to two levels of UV-B
      radiation (T1: 0.15 W/m2 and T2: 0.35 W/m2) was studied by hydroponics under
      laboratory conditions. After 5 d of UV-B treatment, the aboveground growth
      indices were obviously decreased by 13.2%-44.1% (T1) and 21.4%-49.3% (T2),
      compared to CK, and except active absorption area of roots, the belowground
      indices by 14.1%-35.6% (T1) and 20.3%-42.6% (T2). For Ce+UV-B treatments, the
      aboveground and belowground growth indices were decreased respectively by 4.1%
      23.6%, 5.2% -23.3% (Ce+T1) and 10.8%-28.4%, 7.0%-27.8% (Ce+T2), lower than those
      of UV-B treatments. The decrease of growth indices appeared to be the result of
      changes of physiological processes. Two levels of UV-B radiation induced the
      decrease in chlorophyll content, net photosynthesis rate, transpiration rate,
      stomatal conductance and water use efficiency by 11.2%-25.9% (T1) and 20.9%-56.9%
      (T2), whereas increase in membrane permeability and activities of antioxidant
      enzymes including superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD)
      by 6.9%, 22.8%, 21.5%, 9.5% (T1) and 36.6%, 122.3%, 103.5%, 208.9% (T2),
      respectively. The reduction of the photosynthetic parameters in Ce+UV-B
      treatments was lessened to 3.2%-13.8% (Ce+T1) and 4.9%-27.6% (Ce+T2), and the
      increase of membrane permeability and activities of antioxidant enzymes except
      POD in the same treatments were lessened to 2.4%, 8.4%, 6.6% (Ce+T1) and 30.1%,
      116.7%, 75.4% (Ce+T2). These results indicate that the regulative effect of Ce on
      photosynthesis and antioxidant enzymatic function is the ecophysiological basis
      of alleviating the suppression of UV-B radiation on growth of seedlings.
      Furthermore, the protective effect of Ce on seedlings exposed to T1 level of UV-B
      radiation is superior to T2 level.

PMID- 20050561
TI  - Does the long-term application of calcium superphosphate lead to an increase of
      the soil rare earth element contents?
AB  - In order to test whether the long-term application of calcium superphosphate
      leads to an increase of the soil rare earth element contents, superphosphate
      fertilized soils were sampled and compared with superphosphate-free soils.
      Spectrophlame inductively coupled argon plasma atomic emission spectrophotometer
      (ICP-AES) was applied to quantify the rare earth elements (REEs). The total rare
      earth element contents in calcium superphosphate from Zhijin County, west part of
      Guizhou Province, China (produced by the sulphuric acid treatment of the
      apatites) are about 2.54 mg/g. Between 38 and 189 gREEs/hm2 per year (available
      for plants, estimated by 2% citric acid) will be introduced into the soil
      solution when applying 320 kg superphosphate/hm2 per year. The long-term
      application of the latter will increase the REE content by about 18% in the soil
      surface layer in these areas. A statistically significant increase of the content
      of the rare earths in some cultivated soils should not be neglected.

PMID- 20050562
TI  - Effect of herbicide acetochlor on cytochrome P450 monooxygenases and GST of
      earthworms Eisenia fetida.
AB  - To assess the sublethal toxicity of the herbicide acetochlor to earthworms and to
      find out biomarkers possible inducted under acetochlor exposure, Eisenia fetida
      was exposed to artificial soils supplemented with different concentrations of
      acetochlor(5, 10, 20, 40 and 80 mg/kg soil). Effects of the acetochlor on
      cytochrome P450 monooxygenases p-nitroanisole O-demethylase (ODM), aldrin
      epoxidase (AE) and glutathione-S-transferases (GSTs) activities were determined.
      The results revealed cytochrome P450 monooxygenases were elevated with increasing
      concentrations of acetochlor, and the AE activity increased significantly
      compared with control at the concentration of 80 mg/kg (P < 0.05). However, ODM
      activity from E. fetida was not induced significantly by acetochlor at all
      treatments (P > 0.05). Sodium dodecyl sulfate-polyacryamide gel electrophoresis
      (SDS-PAGE) showed that one protein band was visualized and no evident differences
      were found in protein profiles between treatments and control. The GST activity
      increased significantly with longer duration(P < 0.05) and increasing
      concentrations of acetochlor exposure (P < 0.05). This study showed that the
      monooxygenases and GSTs activities in E. fetida could be induced by acetochlor,
      and thus, the AE and GST could be used in sublethal assays for soil contamination
      surveys and GST could be used as biomarkers ofacetochlor exposure in E. fetida.

PMID- 20050563
TI  - Isolation, characterization and phylogenetic analysis of a bacterial strain
      capable of degrading acetamiprid.
AB  - An aerobic bacterium, capable of degrading the new chloronicotine pesticide
      acetamiprid, was isolated from the sludge of pesticide factory after successive
      enrichment cultures and named strain FH2 which is a Gram-negative, rod-shaped,
      obligate aerobic organism with ((0.5-0.7) x (1.5-3.0)) microm of cell size and
      with monotrichous flagellum. It was identified as a member of Pseudomonas sp.
      based on morphology, physio-biochemical properties, Biolog GN2, 16S rDNA sequence
      and phylogenetic characteristic analysis. The isolate could grow optimally at pH
      7.0 and 30 degrees C in acetamiprid-mineral medium with 800 mg/L concentration.
      About 53.3% acetamiprid was degraded by strain FH2 after incubation for 14 d in
      acetamiprid-mineral medium and nearly 96.7% degraded when incubated in
      acetamiprid-yeast mineral medium at 30 degrees C for 14 d. This paper describes
      phylogenetic and degradation characterization of a pure bacterium being able to
      mineralize acetamiprid for the first time.

PMID- 20050564
TI  - Experiments and modelling of phenanthrene biodegradation in the aqueous phase by
      a mixed culture.
AB  - Pollution by polycyclic aromatic hydrocarbons(PAHs) is widespread due to
      unsuitable disposal of industrial waste. They are mostly defined as priority
      pollutants by environmental protection authorities worldwide. Phenanthrene, a
      typical PAH, was selected as the target in this paper. The PAH-degrading mixed
      culture, named ZM, was collected from a petroleum contaminated river bed. This
      culture was injected into phenanthrene solutions at different concentrations to
      quantify the biodegradation process. Results show near-complete removal of
      phenanthrene in three days of biodegradation if the initial phenanthrene
      concentration is low. When the initial concentration is high, the removal rate is
      increased but 20%-40% of the phenanthrene remains at the end of the experiment.
      The biomass shows a peak on the third day due to the combined effects of
      microbial growth and decay. Another peak is evident for cases with a high initial
      concentration, possibly due to production of an intermediate metabolite. The pH
      generally decreased during biodegradation because of the production of organic
      acid. Two phenomenological models were designed to simulate the phenanthrene
      biodegradation and biomass growth. A relatively simple model that does not
      consider the intermediate metabolite and its inhibition of phenanthrene
      biodegradation cannot fit the observed data. A modified Monod model that
      considered an intermediate metabolite (organic acid) and its inhibiting reversal
      effect reasonably depicts the experimental results.

PMID- 20050565
TI  - A remote sensing system of vehicle emissions based on tunable diode laser
      technology.
AB  - As being an effective real-time method of monitoring vehicle emissions on-road, a
      remote sensing system based on the tunable diode laser (TDL) technology was
      presented, and the key technologies were discussed. A field test in Guangzhou
      (Guangdong, China) was performed and was found that the factors, such as slope,
      instantaneous speed and acceleration, had significant influence on the detectable
      rate of the system. Based on the results, the proposal choice of testing site was
      presented.

PMID- 20050566
TI  - Determination of hydroxyl radicals in TiO2/Ti photoelectrocatalytic oxidation
      system using Fe(phen)3(2+) spectrophotometry.
AB  - A new method of determining the cumulate concentration of hydroxyl radicals in
      the TiO2/Ti photoelectrocatalytic (PEC) oxidation system was established by o
      phenanthroline-Fe(II)(Fe(phen)3(2+)) spectrophotometry and using anion exchange
      membrane. Fe (phen)3(2+) can be oxidized to o-phenanthroline
      Fe(III)(Fe(phen)3(3+)) by strong oxidization of hydroxyl radicals(*OH). Then the
      cumulate concentration of hydroxyl radicals can be calculated through determining
      the change of the Fe(phen)3(3+) absorbency at 509 nm. In addition, the research
      results showed the production rate of hydroxyl radicals was affected obviously by
      pH of solution, the cumulate concentration of hydroxyl radicals was the largest
      at nearby the initial pH 6.3 (isoelectric point), and the change direction of pH
      after illumination tended to nearby isoelectric point.

PMID- 20050567
TI  - An improved gas chromatography for rapid measurement of CO2, CH4 and N2O.
AB  - Combining improved injector, gas line and valve-driving modules, a GC equipped
      with FID and ECD, could simultaneously measure CH4, CO2 and N2O in an air sample
      within 4 min. Test results showed that the system has high sensitivity,
      resolution and precision; the linear response range of the system meets the
      requirement of in situ flux measurements. Thus, the system is suitable for
      monitoring fluxes of main greenhouse gases in terrestrial ecosystem since it is
      easy to use, efficacious, stable and reliable to collect data.

PMID- 20050568
TI  - Modification of FGD gypsum in hydrothermal mixed salt solution.
AB  - A novel utilization way of the sludge from wet calcium-based flue gas
      desulfurization (FGD) processes has been developed in this paper. This study
      focused on the conversion of the FGD gypsum into alpha-hemihydrate calcium
      sulfate by a hydrothermal salt solution method at atmospheric pressure.
      Experimental study has been carried out in a batch reactor. Qualitative and
      quantitative analyses were made by DSC/TG thermal analysis, SEM, XRD,
      metalloscope and chemical analysis. The experimental results showed that the
      modification of FGD gypsum was controlled by the dissolution and
      recrystallization mechanisms. With the introduction of FGD gypsum the salt
      solution was supersaturated, then crystal nucleus of alpha-hemihydrate calcium
      sulfate were produced in the solution. With the submicroscopic structure of FGD
      gypsum crystal changed, the crystal nucleus grew up into alpha-hemihydrate
      calcium sulfate crystals. Thus, the modification of FGD gypsum was fulfilled.

PMID- 20050569
TI  - Landfill leachate treatment in assisted landfill bioreactor.
AB  - Landfill is the major disposal route of municipal solid waste (MSW) in most Asian
      countries. Leachate from landfill presents a strong wastewater that needs
      intensive treatment before discharge. Direct recycling was proposed as an
      effective alternative for leachate treatment by taking the landfill as a
      bioreactor. This process was proved not only considerably reducing the pollution
      potential of leachate, but also enhancing organic degradation in the landfill.
      However, as this paper shows, although direct leachate recycling was effective in
      landfilled MSW with low food waste fraction (3.5%, w/w), it failed in MSW
      containing 54% food waste, as normally noted in Asian countries. The initial acid
      stuck would inhibit methanogenesis to build up, hence strong leachate was yielded
      from landfill to threaten the quality of receiving water body. We demonstrated
      the feasibility to use an assisted bioreactor landfill, with a well-decomposed
      refuse layer as ex-situ anaerobic digester to reducing COD loading in leachate.
      By doing so, the refuse in simulated landfill column (2.3 m high) could be
      stabilized in 30 weeks while the COD in leachate reduced by 95% (61000 mg/L to
      3000 mg/L). Meanwhile, the biogas production was considerably enhanced, signaling
      by the much greater amount and much higher methane content in the biogas.

PMID- 20050570
TI  - Reaction site and mechanism in the UV or visible light induced TiO2
      photodegradation of Orange G.
AB  - For TiO2 heterogeneous reaction, the reaction site and the detailed mechanism are
      interesting and controversy topics. In this paper, effects of surface
      fluorination of TiO2 on the photocatalytic degradation of an azo dye, Orange
      G(OG) under UV or visible light irradiation were investigated, and the possible
      reaction site and mechanism were elucidated. The adsorption of OG on TiO2 was
      nearly inhibited by fluoride but its UV light induced photodegradation rate was
      greatly increased by a factor of about 2.7, which was due to the more generated
      free hydroxyl radicals. It supported the views that fluoride could desorb the
      oxidant species from surface and that the reaction sites could move to the bulk
      solution. In TiO2/Vis system, the observed inhibition effects of fluorination
      could be interpreted by the competitive adsorption, which provided additional
      evidences that the visible light sensitized photodegradation of dye pollutants on
      the catalyst surface.

PMID- 20050571
TI  - Arsenic and major cation hydrogeochemistry of the Central Victorian (Australia)
      surface waters.
AB  - This paper reports on the major cations (Ca, Mg, Na and K) and arsenic (As)
      compositions of surface waters collected from major creeks, rivers and lakes in
      Central Victoria (Australia). The surface waters were found to be neutral to
      alkaline (pH 6.7-9.4), oxidised (average redox potential (Eh) about 130 mV) and
      showed variable concentrations of dissolved ions (EC, about 51-4386 microS/cm).
      The concentrations of dissolved major cations in surface waters were found to be
      in the order of Na>>Mg>Ca>K and in soils the contents of metals followed an order
      of abundance as: Ca>Mg>>K>Na. While Na was the least abundant in soils, it
      registered the highest dissolved cation in surface waters. Of the four major
      cations, the average concentration of Na (98.7 mg/L) was attributed to the
      weathering of feldspars and atmospheric input. Relatively highly dissolved
      concentrations of Na and Mg compared with the world average values of rivers
      reflected the weathering of rock and soil minerals within the catchments. The As
      soil level is naturally high (linked to lithology) as reflected by high
      background soil values and mining operations are also considered to be a
      contributory factor. Under relatively alkaline-oxidative conditions low mobility
      of dissolved As (average about 7.9 microg/L) was observed in most of the surface
      waters with a few higher values (> 15 microg/L) around a sewage disposal site and
      mine tailings. Arsenic in soils is slowly released into water under alkaline
      and/or lower Eh conditions. The efficient sink of Fe, Al and Mn oxides acts as a
      barrier against the As release under near neutral-oxidising conditions. High As
      content (average about 28.3 mg/kg) in soils was found to be associated with Fe
      hydroxides as revealed by XRD and SEM analysis. The dissolved As concentration
      was found to be below the recommended maximum levels for recreational water in
      all surface waters (lakes and rivers) in the study area. Catchment lithology
      exerted the fundamental control on surface water chemistry. Sites impacted by
      mining waste dumps showed a decline in water quality.

PMID- 20050572
TI  - Adsorption and photocatalytic degradation of bisphenol A using TiO2 and its
      separation by submerged hollowfiber ultrafiltration membrane.
AB  - This study evaluates the adsorption ability of bisphenol A (BPA) on titanium
      dioxide (TiO2) and its effect on the photocatalysis by advanced oxidation process
      using UV radiation and TiO2 photocatalyst. Degradation of BPA was also evaluated
      for the system without adsorption prior to photocatalytic reaction. The
      separation of TiO2 from BPA solution treated by pilot-scale photocatalytic
      reactor (capacity 0.16 m3) was studied using submerged ultrafiltration (UF)
      membrane. It was found that although adsorption capacity of BPA was not high,
      adsorption played an important role in improving the efficiency of
      photocatalysis. On the other hand, during the separation of TiO2 particles from
      aqueous suspension, the permeate flux of the membrane was strongly affected by
      transmembrane pressure and TiO2 dose. The permeate turbidity was decreased below
      1 NTU.

PMID- 20050573
TI  - Effect of adding Lactobacillus plantarum and soluble carbohydrates to swine
      manure on odorous compounds, chemical composition and indigenous flora.
AB  - Manure odor, which results in the increasing complaints and lawsuits, has
      increased the tension among swine producers and surrounding residents. The
      effects of Lactobacillus plantarum and different rates of soluble carbohydrates
      additions to swine manure on odorous compounds, chemical compounds and indigenous
      flora were evaluated. Additions were calculated on dried manure weight basis.
      Variables monitored included ammonia (NH3), hydrogen sulfide (H2S), odor
      offensiveness, pH, ammonium nitrogen (NH4(+)-N), volatile fatty acids (VFAs),
      urease and indigenous flora. The results indicated that the combination of L.
      plantarum and soluble carbohydrates dramatically reduced manure pH. Lower pH
      resulted in the reduction of NH3 volatilization (34.6%-92.4%, P < 0.01), the
      increases of H2S (P < 0.05) and NH4(+)-N (5.3%-17.5%, P < 0.05). In addition, L.
      plantarum and soluble carbohydrates additions significantly reduced odor
      offensiveness, those VFAs related to malodor indicators (valeric acids, 12.3%
      47.7%, P < 0.05; iso-valeric, 3.5%-23.8%) and the main microorganisms responsible
      for odor production, with the number of Eubacteria in swine manure reducing by
      4.9%, 11.6%, 17.4%, 34.1% and 32.2% respectively.

PMID- 20050574
TI  - Emergence and challenges of eco-medicine in France.
AB  - Increasing popularity of eco-medicine and its preliminary recognition by European
      Union raise questions about a clear definition and its practice in European
      countries as its relevance in France.

PMID- 20050575
TI  - [Recent opinions on the role of acidophilic granulocytes in mechanisms of
      immunological defence and in pathogenesis of selected human diseases].
AB  - This article presents human diseases where the main etiological factor is
      hypereosinophily: eosinophilic cystitis - EC, eosinophilic gastrointestinal
      disorders - EGID, which includes eosinophilic esophagitis - EE, and eosinophilic
      gastritis - EG, and finally nasal polyps - NP. A particular stress is put on the
      absence of correlations between circular hypereosinophily and presence of the
      described diseases.

PMID- 20050576
TI  - [Protective role of leptin in acute gastric ulcers].
AB  - There are few data concerning protective effects of leptin on gastric epithelium
      treated with necrotic factors: ethanol, bile salts and hiperosmotic solutions.
      Further investigations are needed to establish the role of hormone leptin in
      gastroprotection and in the process of chronic gastric ulcers healing in animals.
      Exogenous leptin administration plays protective effects against 75% ethanol
      damage in gastric epithelium. Nitric oxide is involved in gastroprotective
      effects of leptin and CCK.

PMID- 20050577
TI  - [Gastric motility disorders in patients after pancreatoduodenectomy].
AB  - The aim of the study was to evaluate effect of pancreatoduodenectomy on the
      gastric motility in patients with pancreatic carcinoma. In the patients with
      cancer pancreatoduodenectomy causes disorders of gastric myoelectric activity,
      gastric motility and autonomic nervous system function. Gastroparesis after
      surgery seems to depend on specific abnormalities in neurohormonal interaction of
      the GI tract.

PMID- 20050578
TI  - Myoelectric and autonomic nervous system activity in patients with irritable
      bowel syndrome.
AB  - Explanation of the main causes of symptoms and dysfunctions in the FGIDs is
      focused on visceral hypersensitivity. Sympathetic stimulation increases
      sensitivity of visceral receptors. Thus overall influences of the autonomic
      nervous system are important not only in regulation of secretion and motility of
      the gastrointestinal tract but also in visceral sensation. The aim of this study
      was to evaluate gastric motility disturbances and changes in the autonomic
      nervous system (ANS) activity in irritable bowel syndrome patients (IBS). Our
      results show changes of the autonomic system activity in patients with IBS:
      decreased parasympathetic and increased sympathetic activity. The patients with
      autonomic dysfunction had also high percentage of dysrrhythmia time. We conclude
      that dyspeptic symptoms in patients with autonomic dysfunction are caused mostly
      by high adrenergic drive resulting in dysrrhythmias and decrease in the EGG
      amplitude.

PMID- 20050579
TI  - [Influence of vagal stimulation by deep breathing and sham feeding on autonomic
      system response in healthy women].
AB  - Sham feeding (SF) opposite to deep breathing (DB) is not standard method for
      testing autonomic nervous system but is widely used for parasympathetic
      stimulation of gastrointestinal secretion and motility. Differences in vagal
      autonomic system response induced by both methods resulted from different
      localization of receptors and cortical and spinal autonomic centers.

PMID- 20050580
TI  - Pathophysiology of erectile dysfunction in men.
AB  - The increase of life intensity and its stressful impact, a great number of
      various risk factors of ED - erectile dysfunction and aging men population lead
      to a high prevalence and incidence of ED worldwide. It is well known that ED in
      men is a condition of heterogenous aetiology, which determines ED substantial
      diagnostic and therapeutic clinical problem. However, in most cases, ED may be
      managed quite well by the primary care physician who has proper understanding of
      the pathophysiology of ED. This article is intended especially for primary care
      physicians. It reviews physiology of erection and then explores pathophysiologic
      changes that are likely to cause inadequate erection, which enables better
      understanding of ED and consequently is essential for appropriate management.

PMID- 20050581
TI  - [Vagal modulation of nociception in experimental model of viscreal pain].
AB  - Systemic control mechanisms of pain are based on interplay between nervous
      autonomic and immune systems. The aim of this study was to examine a possible
      role of the vagus nerve in regulation of nocyception. Peritoneal inflammation
      increased vagal activity. Pretreatment of PTX had an analgesic effect confirmed
      by amount of WT and decreased vagal activity. The vagotomy decreased nociceptive
      threshold.

PMID- 20050582
TI  - [Effects of melatonin on nociception processes in experimentally model of
      neurophatic pain].
AB  - Melatonin (MT) plays an important role in the regulation of physiological and
      neuroendocrine functions, such as control of circadian rhythms and
      synchronization of seasonal reproductive rhythms in mammals. Melatonin shows its
      antinocieeptive effects in a dose - dependent manner. Melatonin is influencing
      the mechanical allodynia but not thermal hyperalogia. Antinociceptive effects of
      melatonin are having the significant connection with the MT2 receptor stimulation
      and activation of the opioid system.

PMID- 20050583
TI  - [Role of pendoxifiline (PTX) in different and cute and chronic models of pain in
      rats].
AB  - Pentoxifilne (PTX) is a non specific inhibitor of cytokines release, which
      suppress mainly TNF production. The aim of this study was to evaluate behavioural
      activity changes in response to acute and chronic nociceptive stimulus. PTX was
      more effective in neuropathic pain than acute pain model. Use of cytokine
      inhibitors might offer new strategies of drug-resistant chronic pain treatment.

PMID- 20050584
TI  - [Evaluation of morphine metabolism in presence of amantadine and dextromethorphan
      in human serum by high performance liquid chromatography coupled with mass
      spectrometry (LC/MS) method].
AB  - In the present study we assessed by LC/MS method the influence of amantadine and
      dextromethorphan on morphine metabolism in humans in order to explain clinically
      observed phenomenon of amplification of analgesic action of morphine by these
      drugs. Neither dextromethorphan nor amantadine influenced the rate of morphine
      degradation and concentration of morphine metabolites. Thus, our results suggest
      pharmacodynamical, not pharmacokinetic mechanism of interaction.

PMID- 20050585
TI  - Ramipril enhances the endogenous hydrogen sulfide tissue concentration in mouse
      heart and brain.
AB  - BACKGROUND: Hydrogen sulfide (H2S) participates in regulation of different
      physiological and pathological processes of cardiovascular system and nervous
      system. The effect of ramipril - tissue specific angiotensin-converting enzyme
      inhibitor (ACEI) - exceeds renin-angiotensin aldosterone system (RAAS) blockade.
      The influence of ACEI on the metabolism of H2S remains obscure. The aim of the
      study is to assess the impact of ramipril administration on the tissue
      concentration of H2S in mouse heart and brain. METHOD: Thirty mice (CBA) of both
      sexes were given intraperitoneal injections of ramipril solution - 0.125 mg (5
      mg/kg - group D1) and 0.25 mg (10 mg/kg - group D2) for 5 consecutive days at the
      same time of the day (10:30 am). Control group received physiological saline in
      portions of the same volume - 0.2 ml. The measurements of the concentration of
      H2S were performed using spectrophotometric modified method of Siegel. RESULTS:
      There has been a significance rise in the tissue concentration of H2S [microg/g]
      in the heart in group D1 (4.91 +/- 0.07 vs 5.54 +/- 0.12; p = 0.005) and group D2
      (4.91 +/- 0.07 vs 5.94 +/- 0.08; p < 0.001) and in the brain in group D1 (0.61 +/
      0.03 vs 0.69 +/- 0.02; p = 0.02) and non-significant increase in the brain D2
      group (0.61 +/- 0.03 vs 0.65 +/- 0.03; p = 0.16). CONCLUSIONS: Ramipril enhances
      the concentration of endogenous H2S in mouse heart and brain.

PMID- 20050586
TI  - The physiological role of the Gomori-positive glia: a new hypothesis.
AB  - On the basis of histological observations of the brains of intact animals and of
      those injected with a sulfur-containing material (cystamine) we propose that the
      main, if not unique, role of the Gomori-positive glia is to scavenge the brain
      for sulfur-containing material because such material when physiologically present
      (e.g. neurophysin) may give rise to free cysteine that is toxic to neurons, being
      a long-recognized neurotoxin.

PMID- 20050587
TI  - Unraveling excited-state dynamics in a polyfluorene-perylenediimide copolymer.
AB  - Insight into the exciton dynamics occurring in a polyfluorene-perylenediimide (PF
      PDI) copolymer with a reaction mixture ratio of 100 fluorene units to 1 N,N'
      bis(phenyl)-1,6,7,12-tetra(p-tert-octylphenoxy)-perylene-3,4,9,10-tetracarboxylic
      acid diimide (PDI) is presented here. Time-correlated single photon counting and
      femtosecond transient absorption spectroscopy measurements on the PF-PDI
      copolymer have been employed to investigate the excited-state properties of the
      polyfluorene subunit where the exciton is localized (PF) and the incorporated PDI
      chromophore. The experimental results were compared with those obtained from a
      polyfluorene polymer (model PF) and a N,N'-bis(2,6-diisopropylphenyl)-1,6,7,12
      tetra(p-tert-octylphenoxy)-perylene-3,4,9,10-tetracarboxylic acid diimide (model
      PDI) which were used as reference compounds. Because of the high polydispersity
      of the PF-PDI copolymer, there is a polymer fraction present that contains no PDI
      chromophores (polyfluorene polymer fraction (PF polymer fraction)), and wide
      field imaging of single polymers chains of the synthesized PF-PDI copolymer was
      used to estimate this PF polymer fraction. Following the primary excitation of
      the PF in the PF-PDI copolymer, energy hopping between PF's can occur. A fraction
      of the energy of the absorbed photons will be transferred to a PDI chromophore
      via energy transfer from a PF. In a polar solvent, a charge transfer state having
      the S(1) of the PDI moiety as a precursor state is found to form with high
      efficiency on a nanosecond time scale. The data suggest that a fraction of the
      absorbed energy is directed, transferred, and used in charge separation,
      providing a clear view of a multistep mechanism of exciton dissociation into
      charges.

PMID- 20050588
TI  - Comprehensive density functional theory study on the mechanism of activation of
      the nonapeptide hormone oxytocin by metal ions.
AB  - The physiological functions of oxytocin (OT) may be activated by bivalent metal
      ions but not by monovalent ones. However, the reason for this phenomenon is
      unknown. Thus, in the present study, theoretical calculations were performed to
      determine the structures and thermochemical properties of OT and related species:
      OT, [OT+H](+), [OT+2H](2+), [OT+M](+/2+), and [OT+M+H](2+/3+) (M(+) = Na(+) and
      K(+), M(2+) = Co(2+), Ni(2+), Mg(2+), Zn(2+), and Ca(2+)). Their structures and
      vibrational frequencies were determined by the density functional theory based
      method. Their relative electronic energies were determined at the BHandHLYP/6
      311G(2df,p) level with proper considerations of the basis set superposition
      errors. The computed structures were used to explain whether the OT species were
      physiologically active or not, and the mechanism of the activation of OT by
      divalent metal ions but not by monovalent metal ions was determined. The relative
      metal ion affinities of OT were found to be responsible for the relative
      effectiveness of divalent metal ions for the OT activation, which were in the
      order of Co(2+) > Ni(2+) > Mg(2+) > Zn(2+), with a minimal effect by Ca(2+).
      Moreover, the recent observation of the coexistence of [OT+H](+), [OT+2H](2+),
      and [OT+Na+H](2+) in solution in the absence of a divalent metal ion and their
      disappearance in the presence of Zn(2+) were also explained by the computed free
      energy changes of the relevant reactions.

PMID- 20050589
TI  - Heats of vaporization of room temperature ionic liquids by tunable vacuum
      ultraviolet photoionization.
AB  - The heats of vaporization of the room temperature ionic liquids (RTILs) N-butyl-N
      methylpyrrolidinium bistrifluorosulfonylimide, N-butyl-N-methylpyrrolidinium
      dicyanamide, and 1-butyl-3-methylimidazolium dicyanamide are determined using a
      heated effusive vapor source in conjunction with single photon ionization by a
      tunable vacuum ultraviolet synchrotron source. The relative gas phase ionic
      liquid vapor densities in the effusive beam are monitored by clearly
      distinguished dissociative photoionization processes via a time-of-flight mass
      spectrometer at a tunable vacuum ultraviolet beamline 9.0.2.3 (Chemical Dynamics
      Beamline) at the Advanced Light Source synchrotron facility. Resulting in
      relatively few assumptions, through the analysis of both parent cations and
      fragment cations, the heat of vaporization of N-butyl-N-methylpyrrolidinium
      bistrifluorosulfonylimide is determined to be DeltaH(vap)(298.15 K) = 195 +/- 19
      kJ mol(-1). The observed heats of vaporization of 1-butyl-3-methylimidazolium
      dicyanamide (DeltaH(vap)(298.15 K) = 174 +/- 12 kJ mol(-1)) and N-butyl-N
      methylpyrrolidinium dicyanamide (DeltaH(vap)(298.15 K) = 171 +/- 12 kJ mol(-1))
      are consistent with reported experimental values using electron impact
      ionization. The tunable vacuum ultraviolet source has enabled accurate
      measurement of photoion appearance energies. These appearance energies are in
      good agreement with MP2 calculations for dissociative photoionization of the ion
      pair. These experimental heats of vaporization, photoion appearance energies, and
      ab initio calculations corroborate vaporization of these RTILs as intact cation
      anion pairs.

PMID- 20050590
TI  - Discrete-state representation of ion permeation coupled to fast gating in a model
      of ClC chloride channels: comparison to multi-ion continuous space Brownian
      dynamics simulations.
AB  - A discrete-state model of chloride ion motion in a ClC chloride channel is
      constructed, following a previously developed multi-ion continuous space model of
      the same system (Cheng, M. H.; Mamonov, A. B.; Dukes, J. W.; Coalson, R. D. J.
      Phys. Chem. B 2007, 111, 5956) that included a simplistic representation of the
      fast gate in this channel. The reducibility of the many-body continuous space to
      the eight discrete-state model considered in the present work is examined in
      detail by performing three-dimensional Brownian dynamics simulations of each
      allowed state-to-state transition in order to extract the appropriate rate
      constant for this process, and then inserting the pairwise rate constants thereby
      obtained into an appropriate set of kinetic master equations. Experimental
      properties of interest, including the rate of Cl(-) ion permeation through the
      open channel and the average rate of closing of the fast gate as a function of
      bulk Cl(-) ion concentrations in the intracellular and extracellular electrolyte
      reservoirs are computed. Good agreement is found between the results obtained via
      the eight discrete-state model versus the multi-ion continuous space model,
      thereby encouraging continued development of the discrete-state model to include
      more complex behaviors observed experimentally in these channels.

PMID- 20050591
TI  - pKa's of ionizable groups and energetics of protein conformational transitions.
AB  - It is well-known that the stability of proteins is pH-dependent because proteins
      contain groups capable of exchanging protons with their environment. In general,
      all conformational transitions of proteins might be expected to exhibit some pH
      dependence. Using structural data for folded and partially unfolded forms of the
      Drosophila melanogaster engrailed homeodomain, we show that knowledge of the
      pK(a)'s of ionizable groups in different structural forms of a protein is not
      sufficient to determine pH-dependence of the free energy of its conformational
      transitions with accuracy better than 1 kcal/mol. We also describe a convenient
      computational approach for predicting expected errors when free energy of
      conformational transition is derived exclusively from the pK(a) values. This
      approach uses the full interaction free energy matrix between the ionizable
      sites, for the two forms of the protein, which can be determined when appropriate
      structural information is available.

PMID- 20050592
TI  - Organic nanostructures with controllable morphology fabricated from mixed
      (phthalocyaninato)(porphyrinato) europium double-decker complexes.
AB  - The self-assembly behavior of two sandwich-type mixed
      (phthalocyaninato)(porphyrinato) europium double-decker complexes, namely
      Eu(Pc)(TClPP) [Pc = phthalocyaninate; TClPP = meso-tetrakis(4
      chlorophenyl)porphyrinate] (1) and optically active (R)- and (S)
      EuH[Pc(OBNP)(2)](TClPP)] [Pc(OBNP)(2) = phthalocyaninate with two aromatic chiral
      binaphthayl units attached at the nonperipheral positions] (2), has been
      comparatively studied. In addition, a hydrophilic additive with intense adhesive
      ability, sodium carboxymethylcellulose (CMC), was also introduced onto the
      sandwich-type self-assembly systems to combine with double-decker molecules to
      induce additional hydrophilic/hydrophobic interaction. In the absence of the
      additive CMC, the double-decker molecules of 1 self-assemble into nanobelts in
      mixed solvent of chloroform and methanol. Introduction of two aromatic chiral
      binaphthayl units onto the nonperipheral positions of phthalocyanine ligand in
      the sandwich-type mixed double-decker complex 2 leads to the formation of tubal
      nanostructures. Observation of significant difference in the circular dichroism
      (CD) spectra of (R)- and (S)-2 in chloroform from their aggregates dispersed in
      methanol confirms the effective intermolecular interaction due to the interplay
      of pi-pi interaction between adjacent double-decker molecules with chiral
      discrimination among chiral side chains at supramolecular level. With addition of
      CMC, cooperation of intrinsic intermolecular pi-pi interaction with additionally
      introduced hydrophilic/hydrophobic interaction between adjacent double-decker
      molecules induces the formation of nanoscale hollow spheres at 45 degrees C
      during the self-assembly process of 1 and 2.

PMID- 20050593
TI  - Assignment of the 6,6'-dioxo-3,3'-biverdazyl ground state by using broken
      symmetry and spectroscopy oriented configuration interaction techniques.
AB  - The singlet-triplet energy differences (DeltaE(ST)) and the Heisenberg-Dirac-van
      Vleck exchange parameter (J) of 6,6'-dioxo-3,3'-biverdazyl (BVD) have been
      studied by hybrid density functional (HDF), broken symmetry (BS), and
      spectroscopy oriented configuration interaction (SORCI) methods. Energy surface
      scans as a function of the dihedral angle between the two verdazyl rings
      (phi(N2C3C3'N2')) have been performed. The BS computations predict an
      antiferromagnetic ground state. However, the diradical index (R(BS)) ranges from
      97.5 to 99.9%, implying that the interactions between the two unpaired electrons
      are very weak. To calculate J and DeltaE(ST), the multireference character
      introduced by these weak spin-spin interactions must be taken into account.
      Consequently, multireference difference dedicated configuration interaction
      (MRDDCI) methods, as implemented in the SORCI procedure, are used. The in-plane
      pi (IPpi), out-of-plane pi (OPpi), and sigma configurations are included in the
      CI expansions in a balanced fashion. The OPpi-OPpi and OPpi-IPpi overlaps are the
      predominant factors that influence the J and DeltaE(ST) as a function of
      phi(N2C3C3'N2') and cause them to peak around 40 and 140 degrees. In these
      regions, the antiferromagnetic interactions are minimal, and the MRDDCI methods
      predict a triplet ground state. At phi(N2C3C3'N2') = 0,
      DeltaE(ST)[MRDDCI3(14,12)] is in excellent agreement with that of 1,1',5,5'
      tetramethyl-6,6'-dioxo-3,3'-biverdazyl determined experimentally from electron
      paramagnetic resonance (EPR) spectroscopy and differs only by 2.3%. Furthermore,
      DeltaE(ST)[MRDDCI3(14,12)] is consistently smaller than J(Y) as the verdazyl
      rings rotate with respect to each other. This corroborates the theory that the
      HDF-BS technique increases the singlet-triplet energy gap and favors the singlet
      state. Because the SORCI method is specifically designed for large molecules, the
      present very good results open the way for the computation of the magnetic
      properties of larger molecules by the SORCI method. To the best of our knowledge,
      this is the first time that DeltaE(ST) has been computed by the MRDDCI3 method by
      utilizing such a large CI reference space for a molecule of this size.

PMID- 20050594
TI  - Temperature and pressure dependence of the reaction 2CF3 (+ M) <==> C2F6 (+ M).
AB  - Limiting low- and high-pressure rate coefficients as well as full falloff curves
      have been modeled by unimolecular rate theory for the recombination reaction
      2CF(3) (+ M) --> C(2)F(6) (+ M) and the reverse dissociation of C(2)F(6). The
      results are compared with experimental data from the literature. Although there
      are considerable discrepancies (up to a factor of 5) between various experimental
      data near 300 K and the database for high temperatures is still limited, we try
      to conclude on the temperature dependence of the high-pressure rate coefficient.
      We suggest that there is only a small and probably positive temperature
      coefficient of the latter quantity. The present theoretical modeling seems to be
      in agreement with this experimental result, but it is in disagreement with
      conclusions from earlier theoretical work. The difference is attributed to
      different empirical assumptions about the anisotropy of the potential. It is
      shown that nearly all previous experiments (except high-temperature shock wave
      and very low pressure pyrolysis/photolysis experiments) correspond to nearly
      limiting high-pressure conditions.

PMID- 20050595
TI  - Activation of retinal guanylyl cyclase RetGC1 by GCAP1: stoichiometry of binding
      and effect of new LCA-related mutations.
AB  - Retinal membrane guanylyl cyclase (RetGC) and Ca(2+)/Mg(2+) sensor proteins
      (GCAPs) control the recovery of the photoresponse in vertebrate photoreceptors,
      through their molecular interactions that remain rather poorly understood and
      controversial. Here we have determined the main RetGC isozyme (RetGC1):GCAP1
      binding stoichiometry at saturation in cyto, using fluorescently labeled RetGC1
      and GCAP1 coexpressed in HEK293 cells. In a striking manner, the equimolar
      binding of RetGC1 with GCAP1 in transfected HEK293 cells typical for wild-type
      RetGC1 was eliminated by a substitution, D639Y, in the kinase homology domain of
      RetGC1 found in a patient with a severe form of retinal dystrophy, Leber
      congenital amaurosis (LCA). A similar effect was observed with another LCA
      related mutation, R768W, in the same domain of RetGC1. In contrast to the
      completely suppressed binding and activation of RetGC1 by Mg(2+)-liganded GCAP1,
      neither of these two mutations eliminated the GCAP1-independent activity of RetGC
      stimulated by Mn(2+). These results directly implicate the D639 (and possibly
      R768)-containing portion of the RetGC1 kinase homology domain in its primary
      recognition by the Mg(2+)-bound activator form of GCAP1.

PMID- 20050596
TI  - Technique for real-time measurements of endothelial permeability in a
      microfluidic membrane chip using laser-induced fluorescence detection.
AB  - Characterizing permeability of the endothelium that lines blood vessels and heart
      valves provides fundamental physiological information and is required to evaluate
      uptake of drugs and other biomolecules. However, current techniques used to
      measure permeability, such as Transwell insert assays, do not account for the
      recognized effects of fluid flow-induced shear stress on endothelial permeability
      or are inherently low-throughput. Here we report a novel on-chip technique in a
      two-layer membrane-based microfluidic platform to measure real-time permeability
      of endothelial cell monolayers on porous membranes. Bovine serum albumin (a model
      protein) conjugated with fluorescein isothiocyanate was delivered to an upper
      microchannel by pressure-driven flow and was forced to permeate a poly(ethylene
      terephthalate) membrane into a lower microchannel, where it was detected by laser
      induced fluorescence. The concentration of the permeate at the point of detection
      varied with channel flow rates in agreement to less than 1% with theoretical
      analyses using a pore flow model. On the basis of the model, a sequential flow
      rate stepping scheme was developed and applied to obtain the permeability of cell
      free and cell-bound membrane layers. This technique is a highly sensitive, novel
      microfluidic approach for measuring endothelial permeability in vitro, and the
      use of micrometer-sized channels offers the potential for parallelization and
      increased throughput compared to conventional shear-based permeability
      measurement methods.

PMID- 20050597
TI  - Toward verdazyl radical-based materials: ab initio inspection of potential
      organic candidates for spin-crossover phenomenon.
AB  - The origin of magnetic interactions in verdazyl-based radical stackings is
      examined using ab initio wave function and density functional theory (DFT)
      calculations. Starting from the reported crystal structure of the 1,1'
      bis(verdazyl)ferrocene diradical compound, the singlet-triplet energy difference
      has been evaluated on the basis of multireference difference dedicated
      configurations interaction calculations and suggested the innocent role of the
      ferrocene spacer. Using the underlying pi-dimer verdazyl structures, the J
      variations and potential energy surfaces of parallel and antiparallel face-to
      face arrangements have been studied with respect to the verdazyl-verdazyl
      separation to evaluate the Coulomb repulsion U and bandwidth W. While coupled
      cluster CCSD(T) calculations are suggestive of a weak bond formation in both
      dimer arrangements (approximately 40 kJ mol(-1)), the DFT approach fails to
      reproduce the bonding character. The intrinsically delocalized character of the
      magnetic orbitals favors an S = 0 ground state, but importantly, the S = 1 spin
      state is also bound. A typical 0.4 A increase (i.e., 10%) of the verdazyl
      verdazyl equilibrium distance accompanying a 16 kJ mol(-1) adiabatic energy
      difference is calculated between the S = 0 and S = 1 states. In this distance
      separation regime, we finally suggest that either a relative 1.2 A slippage or a
      approximately 42 degrees relative orientation of the verdazyl rings is likely to
      give rise to a high-spin S = 1 ground state. These features are symptomatic of a
      bistable system, and an interpretation of the exchange interaction in verdazyl pi
      dimer structures in terms of spin transition is proposed.

PMID- 20050598
TI  - Multicomponent reaction discovery: three-component synthesis of spirooxindoles.
AB  - The Lewis acid-catalyzed, three-component reaction of isatin and two 1,3
      dicarbonyl compounds is reported. Reactions proceed with high efficiency under
      mild reaction conditions and with good functional group tolerance to afford
      spirooxindole pyranochromenedione derivatives.

PMID- 20050599
TI  - Planned failures from the principle of maximum site occupancy in lanthanide
      helicates.
AB  - Despite the recent emergence of a toolbox fitted with microscopic thermodynamic
      descriptors for predicting the stabilities and speciations of polynuclear
      complexes in solution, the discovery of novel or unusual type of metal-ligand
      assemblies in metallosupramolecular chemistry still often relies on serendipity.
      In order to highlight the novel perspectives offered by a rational exploitation
      of these thermodynamic parameters, the segmental bis-tridentate ligands L7 and L8
      have been designed for providing effective molarities upon reaction with
      trivalent lanthanides, Ln(III), so small that the saturated binuclear triple
      stranded helicates [Ln(2)(Lk)(3)](6+), which obey the well-respected principle of
      maximum site occupancy, cannot be detected in solution because of their
      deliberately planned instabilities. The hierarchical evolution of the effective
      molarities with an increasing number of ligand strands in these complexes indeed
      favors the formation of the alternative unsaturated single-stranded
      [Ln(2)(Lk)](6+) and double-stranded [Ln(2)(Lk)(2)](6+) complexes, whose relative
      speciations in solution depend on the nature of the binding sites introduced into
      the segmental ligand.

PMID- 20050600
TI  - Synthesis of polysubstituted 5-aminooxazoles from alpha-diazocarbonyl esters and
      alpha-isocyanoacetamides.
AB  - A novel and efficient reaction for the synthesis of 2-keto-5-aminooxazoles is
      developed. The entire sequence is realized by simply heating a xylene solution of
      alpha-diazocarbonyl esters and alpha-isocyanoacetamides without any promoters. A
      possible mechanism for the entire sequence is proposed.

PMID- 20050601
TI  - Discrete mercury(II) complexes, one-dimensional and palladium(II)-mediated two
      dimensional silver(I) coordination polymers of NS2-macrocycle: synthesis and
      structural characterization.
AB  - A range of thiaphilic mononuclear (Hg(2+) and Ag(+)) and heterobinuclear
      (Ag(+)/Pd(2+)) complexes (1-6) of an NS(2)-donor macrocycle L with discrete and
      networked forms were prepared and structurally characterized. Reaction of L with
      HgCl(2) afforded a unique 1:1 (cationic/anionic) complex [Hg(2)(L)Cl(5)][Hg(L)Cl]
      (1). Reaction of L with Hg(ClO(4))(2) yielded the sandwich-type 1:2 (metal-to
      ligand) complex [Hg(L)(2)](ClO(4))(2) (2). Contrasting with the mercury(II)
      salts, the reactions of L with AgX (X = NO(3)(-) and CF(3)SO(3)(-)) yielded an
      isostructural one-dimensional (1D) zigzag networks [Ag(L)X](n) (3; X = NO(3)(-)
      and 4; X = CF(3)SO(3)(-)) in which each ring of L is exo-coordinated via two S
      atoms and one N atom to a silver ion which is also bound to one S atom in the
      neighboring L such that the overall coordination geometry about each silver is
      four-coordinate. Whereas, reaction of L with K(2)PdCl(4) gave a discrete
      exocyclic complex 5, [cis-Cl(2)Pd(L)]. Through a successive reaction of the
      complex 5 with AgNO(3), a heterobinuclear two-dimensional (2D) coordination
      polymer 6, [Pd(L)Ag(2.5)(NO(3))(4.5)(H(2)O)(0.5)](n), utilizing exocyclic Pd(II)
      and Ag(I) was isolated and characterized.

PMID- 20050602
TI  - Structural and functional studies of Aspergillus clavatus N(5)
      carboxyaminoimidazole ribonucleotide synthetase .
AB  - N(5)-Carboxyaminoimidazole ribonucleotide synthetase (N(5)-CAIR synthetase), a
      key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of
      aminoimidazole ribonucleotide (AIR) to N(5)-CAIR. To date, this enzyme has been
      observed only in microorganisms, and thus, it represents an ideal target for
      antimicrobial drug development. Here we report the cloning, crystallization, and
      three-dimensional structural analysis of Aspergillus clavatus N(5)-CAIR
      synthetase solved in the presence of either Mg(2)ATP or MgADP and AIR. These
      structures, determined to 2.1 and 2.0 A, respectively, revealed that AIR binds in
      a pocket analogous to that observed for other ATP-grasp enzymes involved in
      purine metabolism. On the basis of these models, a site-directed mutagenesis
      study was subsequently conducted that focused on five amino acid residues located
      in the active site region of the enzyme. These investigations demonstrated that
      Asp 153 and Lys 353 play critical roles in catalysis without affecting substrate
      binding. All other mutations affected substrate binding and, in some instances,
      catalysis as well. Taken together, the structural and kinetic data presented here
      suggest a catalytic mechanism whereby Mg(2)ATP and bicarbonate first react to
      form the unstable intermediate carboxyphosphate. This intermediate subsequently
      decarboxylates to CO(2) and inorganic phosphate, and the amino group of AIR,
      through general base assistance by Asp 153, attacks CO(2) to form N(5)-CAIR.

PMID- 20050603
TI  - Regioselective synthesis of tert-allylic ethers via gold(I)-catalyzed
      intermolecular hydroalkoxylation of allenes.
AB  - A highly regioselective method towards tertiary allylic ethers via gold(I)
      catalyzed intermolecular hydroalkoxylation of allenes is disclosed. Preventing
      subsequent isomerization of the tertiary allylic ether products to primary
      allylic ethers appears to be the key to achieving high regioselectivities.

PMID- 20050604
TI  - Use of task-specific ionic liquid for selective electrocatalytic fluorination.
AB  - Highly selective indirect anodic fluorination of organic compounds was
      successfully carried out for the first time by using a task-specific ionic liquid
      of iodoarene as a mediator in ionic liquid hydrogen fluoride salts.

PMID- 20050605
TI  - Synthesis and characterization of a uranium(III) complex containing a redox
      active 2,2'-bipyridine ligand.
AB  - Hydrotris(3,5-dimethylpyrazolyl)borate uranium(III) diiodide derivatives have
      been prepared as an entry into low-valent uranium chemistry with these ligands.
      The bis(tetrahydrofuran) adduct, Tp*UI(2)(THF)(2) (1) (Tp* = hydrotris(3,5
      dimethylpyrazolyl)borate), was synthesized by addition of sodium hydrotris(3,5
      dimethylpyrazolyl)borate (NaTp*) to an equivalent of UI(3)(THF)(4). Addition of
      2,2'-bipyridine (2,2'-bpy) to 1 displaced the THF molecules producing
      Tp*UI(2)(2,2'-bpy) (2). Both derivatives were characterized by (1)H NMR and IR
      spectroscopies, magnetic measurements, and X-ray crystallography. Reduction of
      both species was attempted with two equivalents of potassium graphite. The
      reduction of 1 did not result in a clean product, but rather decomposition and
      ligand redistribution. However, compound 2 was reduced to form Tp*(2)U(2,2'-bpy),
      3, which is composed of a uranium(III) ion with a radical monoanionic bipyridine
      ligand. This was confirmed by X-ray crystallography, which revealed distortions
      in the bond lengths of the bipyridine consistent with reduction. Further support
      was obtained by (1)H NMR spectroscopy, which showed resonances shifted far
      upfield, consistent with radical character on the 2,2'-bipyridine ligand. Future
      studies will explore the reactivity of this compound as well as the consequences
      for redox-activity in the bipyridine ligand.

PMID- 20050606
TI  - Kinetic and CD/MCD spectroscopic studies of the atypical, three-His-ligated, non
      heme Fe2+ center in diketone dioxygenase: the role of hydrophilic outer shell
      residues in catalysis.
AB  - Diketone cleaving enzyme (Dke1) is a dioxygenase with an atypical, three
      histidine-ligated, mononuclear non-heme Fe(2+) center. To assess the role in
      enzyme catalysis of the hydrophilic residues in the active site pocket, residues
      Glu98, Arg80, Tyr70, and Thr107 were subjected to mutational analysis. Steady
      state and pre-steady state kinetics indicated a role for Glu98 in promoting both
      substrate binding and O(2) reduction. Additionally, the Glu98 substitution
      eliminated the pH dependence of substrate binding (k(cat)(app)/K(M)(app)-pH
      profile) present in wild-type Dke1 (pK(a) = 6.3 +/- 0.4 and 8.4 +/- 0.4). MCD
      spectroscopy revealed that the Glu98 --> Gln mutation leads to the conversion of
      the six-coordinate (6C) resting Fe(2+) center present in the wild-type enzyme at
      pH 7.0 to a mixture of five-coordinate (5C) and 6C sites. The 6C geometry was
      restored with a pH shift to 9.5 which also resulted in ligand field (LF) energy
      splittings identical to that found for wild-type (WT) Dke1 at pH 9.5. In WT Dke1,
      these LF transitions are shifted up in energy by approximately 300 cm(-1) at pH
      9.5 relative to pH 7.0. These data, combined with CD pH titrations which reveal a
      pK(a) of approximately 8.2 for resting WT Dke1 and the Glu98 --> Gln variant,
      indicate the deprotonation of a metal-ligated water. Together, the kinetic and
      spectroscopic data reveal a stabilizing effect of Glu98 on the 6C geometry of the
      metal center, priming it for substrate ligation. Arg80 and Tyr70 are shown to
      promote O(2) reduction, while Thr107 stabilizes the Fe(II) cofactor.

PMID- 20050607
TI  - Effect of cholesterol on electrostatics in lipid-protein films of a pulmonary
      surfactant.
AB  - We report the changes in the electrical properties of the lipid-protein film of
      pulmonary surfactant produced by excess cholesterol. Pulmonary surfactant (PS) is
      a complex lipid-protein mixture that forms a molecular film at the interface of
      the lung's epithelia. The defined molecular arrangement of the lipids and
      proteins of the surfactant film gives rise to the locally highly variable
      electrical surface potential of the interface, which becomes considerably altered
      in the presence of cholesterol. With frequency modulation Kelvin probe force
      microscopy (FM-KPFM) and force measurements, complemented by theoretical
      analysis, we showed that excess cholesterol significantly changes the electric
      field around a PS film because of the presence of nanometer-sized electrostatic
      domains and affects the electrostatic interaction of an AFM probe with a PS film.
      These changes in the local electrical field would greatly alter the interaction
      of the surfactant film with charged species and would immediately impact the
      manner in which inhaled (often charged) airborne nanoparticles and fibers might
      interact with the lung interface.

PMID- 20050608
TI  - In situ STM revelation of the adsorption and polymerization of aniline on Au(111)
      electrode in perchloric acid and benzenesulfonic acid.
AB  - In situ scanning tunneling microscopy (STM) was used to study the adsorption and
      polymerization of aniline on Au(111) single-crystal electrode in 0.1 M perchloric
      acid and 0.1 M benzenesulfonic acids (BSA) containing 30 mM aniline,
      respectively. At the onset potential of aniline's oxidation, approximately 0.8 V
      [vs reversible hydrogen electrode], aniline molecules were adsorbed in highly
      ordered arrays, designated as (3 x 2 square root(3)) and (4 x 2 square root(3))
      in perchloric acid and BSA, respectively. These structures consisted of
      intermingled aniline molecules and perchlorate or BSA(-) anions zigzagging in the
      <110> directions in HClO(4) and in the <121> directions in BSA. The coverage of
      aniline admolecule on Au(111) was lower in BSA than in HClO(4). Raising the
      potential to 0.9 V or more positive values triggered the oxidation and
      polymerization of aniline. With aniline molecules arranging in a way similar to
      the backbone of PAN in HClO(4), they readily coupled with each other to produce
      linear polymeric chains aligned predominantly in the 110 directions of the
      Au(111). Compared with the results observed in H(2)SO(4) (Lee et al. J. Am. Chem.
      Soc. 2009, 131, 6468), the rate of polymerization was slower in HClO(4) and the
      produced PAN molecules tended to aggregate on the Au(111) electrode. PAN
      molecules generated in HClO(4) were anomalously shorter than those formed in
      H(2)SO(4). In 0.1 M BSA, PAN molecules produced by small overpotential (eta < 100
      mV) could assume linear chains or 3D aggregates, depending on [aniline]. These
      results revealed molecular level details in electropolymerization of aniline,
      highlighting the important role of anion in controlling the conformation of PAN
      molecules and the texture of PAN film.

PMID- 20050609
TI  - Improved method for counting DNA molecules on biofunctionalized nanoparticles.
AB  - In order to accurately determine low numbers (1-100) of immobilized ssDNA
      molecules at a single, silica 250 nm nanoparticle surface, we hereby propose an
      integrated approach combining classic single molecule confocal microscopy (SMCM),
      that is, stepwise photobleaching of labeled ssDNA, with modified total internal
      reflection fluorescence microscopy (mTIRF). We postulate that SMCM alone is
      unable to exactly account for all labeled ssDNA because of inherent laser
      polarization effects; that is, perpendicularly oriented molecules to the sample
      surface are not (or are only slightly) susceptible to laser excitation and thus
      are invisible in a classic photobleaching experiment. The SMCM method accounts
      for at best two-thirds (68%) of the present ssDNA molecules. The principle of the
      mTIRF technique, which relies on the creation of highly inclined illumination
      combined with part of the laser remaining in normal Kohler illumination, enables
      accurate counting of SMCM invisible molecules. The combined approach proposed
      here circumvents the polarization issue and allows a complete single molecule
      counting on individual nanoparticles, fully in line with bulk measurements, as
      will be demonstrated.

PMID- 20050610
TI  - Simple rectangular columnar phase of goethite nanorods and its martensitic
      transition to the centered rectangular columnar phase.
AB  - Using high-resolution small-angle X-ray scattering, we observed a new type of the
      columnar phase with a simple rectangular (R(S)) structure in colloidal goethite
      dispersions. Furthermore, it displays a martensitic transition into the usual
      centered rectangular (R(C)) structure in an external magnetic field. The findings
      are rationalized in terms of entropic effects within a simple cell model. We
      interpret the results as an effect of the particle shape and the available
      degrees of freedom on the delicate balance between the space available for
      particle translations and rotations within the two structures.

PMID- 20050611
TI  - Influence of nylon 6 in I3(-)/I(-) redox electrolyte on the photovoltaic
      performance and stability of dye-sensitized solar cells.
AB  - Nylon 6 fibers are used, for the first time, in dye-sensitized solar cells
      (DSSCs). The overall energy conversion efficiency obtained with 0.18 M nylon 6
      reaches 6.2%, which is comparable to that (6.7%) obtained without adding nylon 6
      on the day of cell fabrication. However, it is found that the long-term stability
      of the DSSCs with nylon 6 is superior to that of a reference electrolyte as a
      result of the complexation of nylon 6 with I(3)(-). Furthermore, nylon 6 is found
      to be a corrosion inhibitor for silver metal in the electrolyte containing I(3)(
      ).

PMID- 20050612
TI  - Emerging applications of riboswitches in chemical biology.
AB  - Living systems use RNA sequences known as riboswitches to detect the
      concentrations of small-molecule metabolites within cells and to regulate the
      expression of genes that produce these metabolites. Like their natural
      counterparts, synthetic riboswitches also regulate gene expression in response to
      small molecules. Because synthetic riboswitches can be engineered to respond to
      nonendogenous small molecules, they are powerful tools for chemical and synthetic
      biologists interested in understanding and reprogramming cellular behavior. In
      this review, we present an overview of natural riboswitches, highlight recent
      studies toward developing synthetic riboswitches and provide an overview of
      emerging applications of these RNA switches in chemical biology.

PMID- 20050613
TI  - Light-activated gene expression directs segregation of co-cultured cells in
      vitro.
AB  - Light-directed gene patterning methods have been described as a means to regulate
      gene expression in a spatially and temporally controlled manner. Several methods
      have been reported that use photocaged forms of small molecule effectors to
      control ligand-dependent transcription factors. Whereas these methods offer many
      advantages including high specificity and transient light-sensitivity, the free
      diffusion of the uncaged effector can limit both the magnitude and resolution of
      localized gene induction. Methods to date have been limited by the small fraction
      of irradiated cells that have expression levels significantly above uninduced
      background and have not been shown to affect a defined biological response. The
      tetracycline-dependent transactivator/transrepressor system, RetroTET-ART,
      combined with a photocaged form of doxycycline (NvOC-Dox) can be used to form
      photolithographic patterns of induced expression wherein up to 85% of the
      patterned cells show expression levels above uninduced regions. The efficiency
      and inducibility of the RetroTET-ART system allows one to quantitatively measure
      the limits of resolution and the relative induction levels mediated by a small
      molecule photocaged effector for the first time. Well-defined patterns of
      reporter genes were reproducibly formed within 6-36 h with feature sizes as small
      as 300 microm. After photo-patterning, NvOC-Dox can be rapidly removed, rendering
      cells photoinsensitive and allowing one to monitor GFP product formation in real
      time. Patterned co-expression of the cell surface ligand ephrin A5 on cell
      monolayers creates well-defined patterns that are sufficient to direct and
      segregate co-cultured cells via either attractive or repulsive signaling cues.
      The ability to direct the arrangement of cells on living cell monolayers through
      the action of light may serve as a model system for engineering artificial
      tissues.

PMID- 20050615
TI  - Divergence of biochemical function in the HAD superfamily: D-glycero-D-manno
      heptose-1,7-bisphosphate phosphatase (GmhB).
AB  - D-Glycero-d-manno-heptose-1,7-bisphosphate phosphatase (GmhB) is a member of the
      histidinol-phosphate phosphatase (HisB) subfamily of the haloalkanoic acid
      dehalogenase (HAD) enzyme superfamily. GmhB supports two divergent biochemical
      pathways in bacteria: the d-glycero-d-manno-heptose-1alpha-GDP pathway (in S
      layer glycoprotein biosynthesis) and the l-glycero-d-manno-heptose-1beta-ADP
      pathway (in lipid A biosynthesis). Herein, we report the comparative analysis of
      substrate recognition in selected GmhB orthologs. The substrate specificity of
      the l-glycero-d-manno-heptose-1beta-ADP pathway GmhB from Escherichia coli K-12
      was evaluated using hexose and heptose bisphosphates, histidinol phosphate, and
      common organophosphate metabolites. Only d-glycero-d-manno-heptose 1beta,7
      bisphosphate (k(cat)/K(m) = 7 x 10(6) M(-1) s(-1)) and d-glycero-d-manno-heptose
      1alpha,7-bisphosphate (k(cat)/K(m) = 7 x 10(4) M(-1) s(-1)) displayed
      physiologically significant substrate activity. (31)P NMR analysis demonstrated
      that E. coli GmhB selectively removes the C(7) phosphate. Steady-state kinetic
      inhibition studies showed that d-glycero-d-manno-heptose 1beta-phosphate (K(is) =
      60 microM, and K(ii) = 150 microM) and histidinol phosphate (K(is) = 1 mM, and
      K(ii) = 6 mM), while not hydrolyzed, do in fact bind to E. coli GmhB, which leads
      to the conclusion that nonproductive binding contributes to substrate
      discrimination. High catalytic efficiency and a narrow substrate range are
      characteristic of a well-evolved metabolic enzyme, and as such, E. coli GmhB is
      set apart from most HAD phosphatases (which are typically inefficient and
      promiscuous). The specialization of the biochemical function of GmhB was examined
      by measuring the kinetic constants for hydrolysis of the alpha- and beta-anomers
      of d-glycero-d-manno-heptose 1beta,7-bisphosphate catalyzed by the GmhB orthologs
      of the l-glycero-d-manno-heptose 1beta-ADP pathways operative in Bordetella
      bronchiseptica and Mesorhizobium loti and by the GmhB of the d-glycero-d-manno
      heptose 1alpha-GDP pathway operative in Bacteroides thetaiotaomicron. The results
      show that although each of these representatives possesses physiologically
      significant catalytic activity toward both anomers, each displays substantial
      anomeric specificity. Like E. coli GmhB, B. bronchiseptica GmhB and M. loti GmhB
      prefer the beta-anomer, whereas B. thetaiotaomicron GmhB is selective for the
      alpha-anomer. By determining the anomeric configuration of the physiological
      substrate (d-glycero-d-manno-heptose 1,7-bisphosphate) for each of the four GmhB
      orthologs, we discovered that the anomeric specificity of GmhB correlates with
      that of the pathway kinase. The conclusion drawn from this finding is that the
      evolution of the ancestor to GmhB in the HisB subfamily provided for
      specialization toward two distinct biochemical functions.

PMID- 20050614
TI  - Structural determinants of substrate recognition in the HAD superfamily member D
      glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB) .
AB  - The haloalkanoic acid dehalogenase (HAD) enzyme superfamily is the largest family
      of phosphohydrolases. In HAD members, the structural elements that provide the
      binding interactions that support substrate specificity are separated from those
      that orchestrate catalysis. For most HAD phosphatases, a cap domain functions in
      substrate recognition. However, for the HAD phosphatases that lack a cap domain,
      an alternate strategy for substrate selection must be operative. One such HAD
      phosphatase, GmhB of the HisB subfamily, was selected for structure-function
      analysis. Herein, the X-ray crystallographic structures of Escherichia coli GmhB
      in the apo form (1.6 A resolution), in a complex with Mg(2+) and orthophosphate
      (1.8 A resolution), and in a complex with Mg(2+) and d-glycero-d-manno-heptose
      1beta,7-bisphosphate (2.2 A resolution) were determined, in addition to the
      structure of Bordetella bronchiseptica GmhB bound to Mg(2+) and orthophosphate
      (1.7 A resolution). The structures show that in place of a cap domain, the GmhB
      catalytic site is elaborated by three peptide inserts or loops that pack to form
      a concave, semicircular surface around the substrate leaving group. Structure
      guided kinetic analysis of site-directed mutants was conducted in parallel with a
      bioinformatics study of sequence diversification within the HisB subfamily to
      identify loop residues that serve as substrate recognition elements and that
      distinguish GmhB from its subfamily counterpart, the histidinol-phosphate
      phosphatase domain of HisB. We show that GmhB and the histidinol-phosphate
      phosphatase domain use the same design of three substrate recognition loops
      inserted into the cap domain yet, through selective residue usage on the loops,
      have achieved unique substrate specificity and thus novel biochemical function.

PMID- 20050616
TI  - Predominant (S)-enantioselective inclusion of aryl methyl sulfoxides by (S)
      isoleucyl-(S)-phenylglycines.
AB  - In terms of chiral recognition for racemic aryl methyl sulfoxides in the solid
      state, three kinds of crystalline (S)-alkylglycyl-(S)-phenylglycines were
      examined as potential dipeptides host molecules. When (S)-alanyl-(S)
      phenylglycines [(S,S)-Ala-Phg] crystallized with aryl methyl sulfoxides, the
      stereochemistry of preferentially included sulfoxides depended on the individual
      shapes of the sulfoxides and the enantiomeric excess was relatively low. Although
      (S)-leucyl-(S)-phenylglycines [(S,S)-Leu-Phg] and (S)-isoleucyl-(S)
      phenylglycines [(S,S)-Ile-Phg] mainly included the S-form of aryl methyl
      sulfoxides, the enantiomeric recognition of (S,S)-Ile-Phg was superior to that of
      (S,S)-Leu-Phg. Single-crystal X-ray analysis of these inclusion compounds
      revealed that the dipeptide molecules self-assembled to form layer structures and
      included sulfoxides between these layers through hydrogen bonding between the
      proton of (+)NH(3) and the oxygen of the sulfoxide. Besides these host-guest
      interactions, the phenyl groups of the sulfoxides interacted with each other
      through the phenyl-phenyl interaction. Two adjacent homochiral sulfoxides make a
      pair having a 2-fold screw axis along the channel cavity. Thus, the self
      recognition of sulfoxides made 2(1) helical column structures and had high
      enantioselectivity.

PMID- 20050617
TI  - Synthesis of 4-substituted 3,3-difluoropiperidines.
AB  - Synthetic strategies toward 4-substituted 3,3-difluoropiperidines were evaluated.
      4-Alkoxymethyl- and 4-aryloxymethyl-3,3-difluoropiperidines were synthesized via
      1,4-addition of ethyl bromodifluoroacetate to 3-substituted acrylonitriles in the
      presence of copper powder, followed by borane reduction of the cyano substituent,
      lactamization, and reduction of the lactam. This method was applied to establish
      the synthesis of N-protected 3,3-difluoroisonipecotic acid, a fluorinated gamma
      amino acid. 4-Benzyloxy-3,3-difluoropiperidine was prepared using an analogous
      methodology and was converted to N-protected 3,3-difluoro-4,4
      dihydroxypiperidine, a compound with high potential as a building block in
      medicinal chemistry.

PMID- 20050618
TI  - Molecular template approach for evolution of conducting polymer nanostructures:
      tracing the role of morphology on conductivity and solid state ordering.
AB  - Here, we report a unique molecular template approach, for the first time, to
      study the evolution of the different types of nanomaterial morphologies such as
      nanofiber, nanorod, nanosphere, and nanotube in a single system without changing
      their chemical composition or polymerization route. A renewable resource
      surfactant was self-organized with aniline (95%) and pyrrole (5%) in water to
      produce white emulsion consisting of long-range cylindrical micellar aggregates.
      The dilution of the emulsion with water resulted in the transformation of
      cylindrical to vesicular aggregates without any phase separation. The size and
      shape of the cylindrical and vesicular template aggregates were confirmed by
      dynamic light scattering and electron microscopic analysis. The chemical
      oxidation of the cylindrical templates produced nanofibers and nanorods, whereas
      hollow spheres and nanotubes were produced by vesicular templates. The nanofibers
      were found as long as 4-5 microm length with 200 nm widths, whereas the nanorods
      were shorter in length (0.5-0.7 microm) with 80-120 nm diameter. The hollow
      spheres were obtained in 1 mum diameter with wall thickness of approximately 80
      nm. The length of the nanotubes was found to vary from 1.2 to 1.8 microm. The
      average wall thickness and inner pore diameter of the nanotubes were found as
      approximately 30 nm and approximately 60 nm, respectively. The size and shape of
      the template aggregates match very well with that of the synthesized
      nanomaterials and provide direct evidence for the template-assisted evolution of
      the nanostructure morphology. NMR, FT-IR and UV-visible spectroscopies were
      utilized to confirm the structure and electronic properties of the nanomaterials.
      Wide angle X-ray diffraction and transmission electron microscopy-electron
      diffraction analysis revealed that the nanotubes possessed three-dimensional
      lamellar-type solid states ordering with high percent crystallinity up to 60%.
      Variable temperature four-probe conductivity measurements of all samples showed
      typical I-V plots. The conductivity of the nanofibers was found one order higher
      than that of nanorod, hollow sphere, and nanotubes at all temperatures. The
      present investigation enabled us to establish the role of various types of
      nanomorphologies on properties of nanomaterials such as conductivity and solid
      state ordering without change in their chemical composition.

PMID- 20050619
TI  - Nonadiabatic histidine dissociation of hexacoordinate heme in neuroglobin
      protein.
AB  - In the present work, density functional theory and canonical nonadiabatic Monte
      Carlo transition state theory have been used to investigate the histidine
      dissociation process from hexacoordinate heme in Ngb protein. The potential
      energy surfaces (PES) of the lowest singlet, triplet, and quintet states are
      calculated by stepwise optimization along with the histidine dissociation
      pathway. Based on the calculated two-dimensional PES, the histidine dissociation
      rates for the spin-forbidden processes via singlet to triplet and singlet to
      quintet transitions have been calculated by the nonadiabatic Monte Carlo
      transition state theory in canonical ensemble. The present study provides a
      quantitative description on spin-forbidden histidine dissociation processes.

PMID- 20050620
TI  - Gas-phase chemistry in inductively coupled plasmas for NO removal from mixed gas
      systems.
AB  - Inductively coupled rf plasmas were used to investigate the removal of NO from a
      variety of gas mixtures. Laser-induced fluorescence and optical emission
      spectroscopy were employed to measure the relative gas-phase density of NO as a
      function of the applied rf power, gas mixture, and catalytic substrate type. In
      general, the overall density of NO decreases as a function of applied rf power in
      both NO and N(2)/O(2) plasmas, but the addition of gases such as H(2)O vapor and
      CH(4), as well as the presence of Au-coated substrates, significantly affects the
      behavior of NO in these systems. Rotational and vibrational temperatures for NO
      were measured using laser-induced fluorescence excitation spectra and optical
      emission spectra. Results show NO vibrational temperatures are about a factor of
      5 higher than rotational temperatures and indicate little dependence on applied
      rf power, feed gas composition, or overall system pressure. Possible mechanisms
      for the observed changes in [NO] as well as the rotational and vibrational
      temperature data are addressed.

PMID- 20050621
TI  - Molecular dynamics of regioregular poly(3-hexylthiophene) investigated by NMR
      relaxation and an interpretation of temperature dependent optical absorption.
AB  - The molecular structure and dynamics of regioregulated poly(3-hexylthiophene)
      (P3HT) were investigated using high-resolution solid-state (13)C nuclear magnetic
      resonance (NMR) and optical absorption spectroscopies. A crystal (C)-plastic
      crystal (PC) transition induced by the molecular motion of the aliphatic side
      group was observed for P3HT in the temperature dependence analysis of (13)C NMR
      spectra and spin-lattice relaxation time (T(1C)). The aliphatic side group motion
      in the crystalline state weakened intermolecular pi-pi interaction, resulting in
      the blue shift of the characteristic absorption of the interchain exciton. Above
      the transition temperature, the thiophene twisting motion induces not only
      further collapsing of the intermolecular interaction but also localizing of the
      intrachain exciton, leading to the blue shift of the absorption of both the inter
      and intrachain exciton.

PMID- 20050622
TI  - Self-assembled nanostructures of homopolymer and diblock copolymer blends in a
      selective solvent.
AB  - Self-assembled nanostructures of amphiphilic block copolymers hold great promise
      for applications in nanomedicine. Blending polymers provides an effective way to
      produce multifunctional drug delivery vesicles at micro- and nanoscales. Here we
      investigate the self-assembly of homopolymer and diblock copolymer blends in a
      selective solvent by using the self-consistent field method. It is found that
      self-assembled nanostructures of different sizes and shapes (e.g., vesicles,
      circle- and line-like micelles, and their mixtures) can be obtained by varying
      the concentration and composition of the diblock copolymer. As the chain length
      or concentration of the homopolymer changes, morphological transitions may occur
      among the different nanostructures. On the basis of a number of simulations under
      various conditions, a phase diagram of aggregate morphologies is constructed with
      respect to the mixture ratio and the homopolymer chain length. The theoretical
      method presented here could be used to design novel nanomedicine carriers and to
      optimize their sizes and shapes for specific biomedical applications.

PMID- 20050623
TI  - QM/MM studies of xanthine oxidase: variations of cofactor, substrate, and active
      site Glu802.
AB  - In continuation of our previous QM/MM study on the reductive half-reaction of
      wild-type xanthine oxidase, we consider the effects of variations in the
      cofactor, the substrate, and the active-site Glu802 residue on the reaction
      mechanism. Replacement of the sulfido ligand in the natural cofactor by an oxo
      ligand leads to a substantial increase in the computed barriers, consistent with
      the experimentally observed inactivity of this modified cofactor, whereas the
      selenido form is predicted to have lower barriers and hence higher activity. For
      the substrate 2-oxo-6-methylpurine, the calculated pathways for three different
      tautomers show great similarity to those found previously for xanthine, contrary
      to claims in the literature that the mechanisms for these two substrates are
      different. Compared with the wild-type enzyme, the conversion of xanthine to uric
      acid follows a somewhat different pathway in the Glu802 --> Gln mutant which
      exhibits a lower overall activity, in agreement with recently published kinetic
      data. The present results confirm the basic stepwise reaction mechanism and the
      orientation of the substrate that has been proposed in our previous QM/MM work on
      aldehyde oxidoreductase and xanthine oxidase.

PMID- 20050624
TI  - Competition of sulphation and carbonation reactions during looping cycles for CO2
      capture by CaO-based sorbents.
AB  - Two types of sorbents are investigated here (natural limestone and highly
      reactive calcium aluminate pellets) to elucidate their reactivity in terms of
      sulphation and carbonation and determine the resulting effect on looping cycles
      for CO(2) capture. The sorbents are tested in a thermogravimetric analyzer (TGA)
      apparatus using typical synthetic flue gas mixtures containing 15% CO(2) and
      various concentrations of SO(2). The sulphation and carbonation conversions were
      determined during sulphation/carbonation/calcination cycles. The sorbent
      morphology and its changes were determined by means of a scanning electron
      microscope (SEM). The results showed that sulphation, that is, the formation of
      CaSO(4) at the sorbent surface, is a cumulative process with increasing numbers
      of reaction cycles, which hinders sorbent ability to capture CO(2). In the case
      of high sorbent reactivity, as determined by its morphology, the unfavorable
      effect of sulphation is more pronounced. Unfortunately, any increase in the
      temperature in the carbonation stage accelerates sulphation more than carbonation
      as a result of higher activation energy for the sulphation reaction. The SEM
      analyses showed that although sulphation and carbonation occur during cycles
      involving calcination, an unreacted core/partially sulphated shell sorbent
      particle pattern is formed. The main outcomes of this research indicate that
      special attention should be paid to the sulphation when more reactive and more
      expensive, synthetic CaO-based sorbents are used for CO(2) capture looping
      cycles. Desulphurization of flue gas before CO(2) capture appears to be essential
      because CO(2) looping cycles are so strongly affected by the presence of SO(2).

PMID- 20050625
TI  - Uranyl adsorption and speciation at the fused silica/water interface studied by
      resonantly enhanced second harmonic generation and the chi(3) method.
AB  - We report the first use of resonantly enhanced second harmonic generation (SHG)
      to study uranyl adsorption at a buried mineral oxide/water interface. Uranyl
      adsorption is studied in real-time, under flow conditions, and in the presence of
      environmentally relevant screening electrolyte concentrations. The in situ SHG
      spectrum of surface-bound uranyl reveals a well-defined resonance at 306 nm. By
      monitoring the SHG response at 306 nm, adsorption isotherms were collected for
      uranyl species at the fused silica/water interface at pH 7, and in the presence
      of aqueous carbonate. The measured adsorption free energies determined by the
      Langmuir isotherm are consistent with physisorption via hydrogen bonding. The
      speciation of the surface-active uranyl species at pH 7 was elucidated via a free
      energy versus interfacial potential analysis, which reveals that the uranyl
      adsorbates are either neutral or univalent cationic species. Complementary
      surface charge density data, obtained using the Eisenthal chi(3) technique,
      reveal that the charge on the ionic uranyl species adsorbing under the
      experimental conditions are positive. It is proposed that a mixture of neutral
      and univalent, cationic uranyl species is surface active at pH 7 and in the
      presence of carbonate ions. Insofar as the experimental conditions model those
      found in natural groundwater systems, the results of this work are valuable to
      the prediction and assessment of uranium pollution transport in groundwater and
      soils. Our thermodynamic results can also serve as important benchmarks for
      computer simulations of U(VI) transport in heterogeneous geochemical
      environments.

PMID- 20050626
TI  - Use of a combination of isotopically coded cross-linkers and isotopically coded N
      terminal modification reagents for selective identification of inter-peptide
      crosslinks.
AB  - Cross-linking combined with mass spectrometry has great potential for determining
      three-dimensional structures of proteins and protein assemblies. One of the main
      analytical challenges of this method is the specific detection and identification
      of the inter-peptide crosslinks in the peptide mixture after enzymatic digestion
      of the cross-linked protein complex. These inter-peptide crosslinks are important
      because they provide the critical distance information needed for structural
      proteomics studies. In this paper, we demonstrate the use of isotopically coded N
      terminal modification (ICNTM) in combination with isotopically coded cross
      linkers (ICCL) for specific detection of inter-peptide crosslinks. Inter-peptide
      crosslinks contain two amino termini, compared to one in the case of free
      peptides, dead-end crosslinks, or intra-peptide crosslinks. Therefore, N-terminal
      modification with a 1:1 mixture of heavy and light isotopically coded reagents
      produces inter-peptide crosslinks with a distinct isotopic signature (a 1:2:1
      ratio). Modification also occurs at the epsilon-amino groups of non-cross-linked
      lysine residues, resulting in two modifications per free lysine-containing
      peptide. However, if ICCL and ICNTM are used together, inter-peptide crosslinks
      can be distinguished from free lysine-containing peptides. Specialized software
      has also been developed for the analysis of ICCL + ICNTM experimental data. This
      procedure, combined with software for data analysis, provides a simple and rapid
      method for specific detection of inter-peptide crosslinks.

PMID- 20050627
TI  - Mechanism of ionic recognition by polymer-supported reagents: immobilized
      tetramethylmalonamide and the complexation of lanthanide ions.
AB  - The mechanism of ionic recognition by polymer-supported reagents is probed with
      cross-linked polystyrene modified with tetramethylmalonamide (TMMA) ligands. The
      substrates are lanthanide ions in 0.001-8 M HCl and HNO(3) solutions. The results
      fall into three regions of acid concentration: low, mid, and high. In HCl,
      distribution coefficients are low in 0.001 to 2 M, increase in 4 and 6 M, and
      then decrease in 8 M HCl. In the low-acid region, the metal ion remains with its
      waters of hydration and does not coordinate to the carbonyl oxygens. As the acid
      concentration exceeds 2 M, protonation of the amide occurs to form an iminium
      moiety, electrostatically attracting the anionic lanthanide complex through ion
      exchange and releasing waters of hydration. At high acid concentration, the
      apparent affinity decreases due to competition by the large excess of chloride
      ions for the ion-exchange sites. The affinity sequence in 6 M HCl is Tb > Dy > Eu
      > Gd > Ho > Sm > Er > Tm > Yb > Lu > Nd > Ce > La. The TMMA-Ln interaction is due
      to recognition since there is a point of maximum affinity across the series
      rather than a monotonic trend. The trends are comparable in HNO(3). A comparison
      of the distribution coefficients at the maxima (6 M HCl and 4 M HNO(3)) shows
      nitrate to have greater values than chloride due to a hydration effect, as also
      indicated by results from H(2)SO(4).

PMID- 20050628
TI  - Accurate modeling of spin-state energetics in spin-crossover systems with modern
      density functional theory.
AB  - The energies of different spin multiplicities of a range of iron complexes are
      computed using modern density functional theory (DFT) methods of the generalized
      gradient approximation (GGA; BP86 and OPBE), meta-GGA (TPSS), hybrid meta-GGA
      (TPSSh), hybrid (B3LYP), and double-hybrid (B2PLYP) types. It is shown that so
      far only the double-hybrid density functional B2PLYP, in conjunction with large
      and flexible basis sets (def2-QZVPP), is able to provide qualitatively correct
      results of spin-state energetics for the investigated non-spin-crossover
      complexes. An energy difference of -6 to 0 kcal/mol is proposed to be indicative
      of spin-crossover behavior.

PMID- 20050629
TI  - Vertex-fused metallaborane clusters: synthesis, characterization and electronic
      structure of [(eta5-C5Me5Mo)3MoB9H18].
AB  - The reaction of the [(eta(5)-C(5)Me(5))MoCl(4)] complex with [LiBH(4).THF] in
      toluene at -70 degrees C, followed by pyrolysis at 110 degrees C, afforded dark
      brown [(eta(5)-C(5)Me(5)Mo)(3)MoB(9)H(18)], 2, in parallel with the known
      [(eta(5)-C(5)Me(5)Mo)(2)B(5)H(9)], 1. Compound 2 has been characterized in
      solution by (1)H, (11)B, and (13)C NMR spectroscopy and elemental analysis, and
      the structural types were unequivocally established by crystallographic studies.
      The title compound represents a novel class of vertex-fused clusters in which a
      Mo atom has been fused in a perpendicular fashion between two molybdaborane
      clusters. Electronic structure calculations employing density functional theory
      yield geometries in agreement with the structure determinations, and on grounds
      of density functional theory calculations, we have analyzed the bonding patterns
      in the structure.

PMID- 20050631
TI  - 2,6-Dithiopurine blocks toxicity and mutagenesis in human skin cells exposed to
      sulfur mustard analogues, 2-chloroethyl ethyl sulfide and 2-chloroethyl methyl
      sulfide.
AB  - Sulfur mustard (bis-(2-chloroethyl)sulfide) is a well-known chemical warfare
      agent that induces debilitating cutaneous toxicity in exposed individuals. It is
      also known to be carcinogenic and mutagenic because of its ability to damage DNA
      via electrophilic attack. We previously showed that a nucleophilic scavenger, 2,6
      dithiopurine (DTP), reacts chemically with several electrophilic carcinogens,
      blocking DNA damage in vitro and in vivo and abolishing tumor formation in a two
      stage mouse skin carcinogenesis model. To assess the potential of DTP as an
      antagonist of sulfur mustard, we have utilized monofunctional chemical analogues
      of sulfur mustard, 2-chloroethyl ethyl sulfide (CEES) and 2-chloroethyl methyl
      sulfide (CEMS), to induce toxicity and mutagenesis in a cell line, NCTC2544,
      derived from a human skin tumor. We show that DTP blocks cytotoxicity in CEMS-
      and CEES-treated cells when present at approximately equimolar concentration. A
      related thiopurine, 9-methyl-6-mercaptopurine, is similarly effective. Correlated
      with this, we find that DTP is transported into these cells and that adducts
      between DTP and CEES are found intracellularly. Using a shuttle vector-based
      mutagenesis system, which allows enumeration of mutations induced in the skin
      cells by a blue/white colony screen, we find that DTP completely abolishes the
      mutagenesis induced by CEMS and CEES in human cells.

PMID- 20050630
TI  - Signaling functions of reactive oxygen species.
AB  - We review signaling by reactive oxygen species, which is emerging as a major
      physiological process. However, among the reactive oxygen species, H(2)O(2) best
      fulfills the requirements of being a second messenger. Its enzymatic production
      and degradation, along with the requirements for the oxidation of thiols by
      H(2)O(2), provide the specificity for time and place that are required in
      signaling. Both thermodynamic and kinetic considerations suggest that among
      possible oxidation states of cysteine, formation of sulfenic acid derivatives or
      disulfides can be relevant as thiol redox switches in signaling. In this work,
      the general constraints that are required for protein thiol oxidation by H(2)O(2)
      to be fast enough to be relevant for signaling are discussed in light of the
      mechanism of oxidation of the catalytic cysteine or selenocysteine in thiol
      peroxidases. While the nonenzymatic reaction between thiol and H(2)O(2) is, in
      most cases, too slow to be relevant in signaling, the enzymatic catalysis of
      thiol oxidation by these peroxidases provides a potential mechanism for redox
      signaling.

PMID- 20050632
TI  - Detoxication of sulfur half-mustards by nucleophilic scavengers: robust activity
      of thiopurines.
AB  - Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare
      since World War I and is well known as an acutely toxic vesicant. It has been
      implicated as a carcinogen after chronic low-level exposure and is known to form
      interstrand cross-links in DNA. Sulfur and nitrogen mustards are currently of
      interest as potential chemical threat agents for terrorists because of ease of
      synthesis. Sulfur mustard and monofunctional analogues (half-mustards, 2
      [chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular
      macromolecules, and thus are potentially subject to scavenging by nucleophilic
      agents. We have determined rate constants for the reaction of four purine
      derivatives that contain nucleophilic thiol moieties with several sulfur-half
      mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9
      methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard
      compounds. At near neutral pH, these thiopurines are much better nucleophilic
      scavengers of mustard electrophiles than other low molecular weight thiols such
      as N-acetyl cysteine and glutathione. Progress curves calculated by numerical
      integration techniques indicate that equimolar concentrations of thiopurine
      provide significant reductions in the overall exposure to the episulfonium ions,
      which are the major reactive, electrophiles produced when sulfur mustards are
      dissolved in aqueous solution.

PMID- 20050633
TI  - Kinetico-mechanistic study of the thermal cis-to-trans isomerization of 4,4'
      dialkoxyazoderivatives in nematic liquid crystals.
AB  - 4,4'-Dialkoxy-substituted azobenzenes are usually required for technical
      applications. Here, we study the mechanism through which the azo-dye thermally
      isomerizes from the unstable cis isomer to the more stable trans isomer when it
      is incorporated in the nematic liquid-crystalline state. We have determined the
      kinetic and thermal activation parameters for this process in different nematic
      environments. Their comparison with those values obtained in isotropic media
      demonstrates that the mechanism through which the thermal cis-to-trans
      isomerization takes place is the inversion pathway in all the physical states
      studied. The nematic order increases the rate of the thermal cis-to-trans
      isomerization process. This fact is related to a cooperative interaction
      established between the mesogen molecules and the azo-dye. This effect is not
      present in the isotropic state.

PMID- 20050634
TI  - Low-energy reaction rate constants for the Ni+-assisted decomposition of
      acetaldehyde: observation of C-H and C-C activation.
AB  - Rate constants for the low-energy Ni(+)-assisted dissociative reaction of
      acetaldehyde have been measured under jet-cooled conditions in the gas phase. The
      rate constants are acquired through monitoring the time dependence of fragment
      Ni(+)CO formation. The decomposition of the precursor Ni(+)-acetaldehyde cluster
      ion proceeds via consecutive, parallel reaction coordinates that originate with
      the Ni(+)-assisted cleavage of either a C-C or an aldehyde C-H bond. The energies
      used to initiate these reactions are well below that required to cleave sigma
      bonds in the isolated acetaldehyde molecule. Direct measurement of the reaction
      kinetics over a range of energies indicates that the rate-limiting step in the
      dissociative mechanism changes at cluster ion internal energies = 17,200 +/- 400
      cm(-1). Arguments are presented that this energy marks the closure of the
      dissociative coordinate that initiates with C-H sigma-bond activation and thus
      provides a measure of the activation energy of this dissociative pathway.

PMID- 20050635
TI  - Activation of R235A mutant orotidine 5'-monophosphate decarboxylase by the
      guanidinium cation: effective molarity of the cationic side chain of Arg-235.
AB  - The R235A mutation at yeast orotidine 5'-monophosphate decarboxylase (OMPDC)
      results in a 1300-fold increase in K(m) and a 14-fold decrease in k(cat) for
      decarboxylation of orotidine 5'-monophosphate, corresponding to a 5.8 kcal/mol
      destabilization of the transition state. There is strong activation of this
      mutant enzyme by added guanidinium cation (Gua(+)): 1 M Gua(+) stabilizes the
      transition state by ca. 3 kcal/mol. This stabilization is due to the binding of
      Gua(+) to the binary E(mut) x OMP complex, with a K(d) of 50 mM, to form the 9
      fold more reactive ternary E(mut) x OMP x Gua(+) complex. The "effective
      molarity" of the cationic side chain of Arg-235 at the wild-type enzyme is
      calculated to be 160 M.

PMID- 20050636
TI  - Comparative study of electrostatic models for the amide-I and -II modes: linear
      and two-dimensional infrared spectra.
AB  - We have carried out a comparative study of five ab initio electrostatic frequency
      maps and a semiempirical model for the amide-I and -II modes. Unrestrained
      molecular dynamics simulation of a 3(10)-helical peptide, Z-Aib-L-Leu-(Aib)(2)
      Gly-OtBu, in CDCl(3) is performed using the AMBER ff99SB force field, and the
      linear and two-dimensional infrared (2D IR) spectra are simulated on the basis of
      a vibrational exciton Hamiltonian model. A new electrostatic potential-based
      amide-I and -II frequency map for N-methylacetamide is developed in this study.
      This map and other maps developed by different research groups are applied to
      calculate the local mode frequencies of the amide linkages in the hexapeptide.
      The simulated amide-I line shape from all models agrees well with the previous
      experimental results on the same system, except for an overall frequency shift.
      In contrast, the simulated amide-II bands are more sensitive to the frequency
      maps. Essential features obtained in the electrostatic models are captured by the
      semiempirical model that takes into account only the intramolecular hydrogen
      bonding effects and solvent shifts. Detailed comparisons between the models are
      also drawn through analysis of the local mode frequency shifts. Among all of the
      maps tested in this study, the new four-site potential map performs quite well in
      simulating the amide-II bands. It properly predicts the effects of hydrogen
      bonding on the amide-I and -II frequencies and reasonably simulates the isotope
      dependent amide-I/II cross peaks upon (13)C=(18)O/(15)N substitutions.

PMID- 20050637
TI  - Phenomenological description of a three-center insertion reaction: an information
      theoretic study.
AB  - Information-theoretic measures are employed to describe the course of a three
      center chemical reaction in terms of detecting the transition state and the
      stationary points unfolding the bond-forming and bond-breaking regions which are
      not revealed in the energy profile. The information entropy profiles for the
      selected reactions are generated by following the intrinsic-reaction-coordinate
      (IRC) path calculated at the MP2 level of theory from which Shannon entropies in
      position and momentum spaces at the QCISD(T)/6-311++G(3df,2p) level are
      determined. Several complementary reactivity descriptors are also determined,
      such as the dipole moment, the molecular electrostatic potential (MEP) obtained
      through a multipole expansion (DMA), the atomic charges and electric potentials
      fitted to the MEP, the hardness and softness DFT descriptors, and several
      geometrical parameters which support the information-theoretic analysis. New
      density-based structures related to the bond-forming and bond-breaking regions
      are proposed. Our results support the concept of a continuum of transient of
      Zewail and Polanyi for the transition state rather than a single state, which is
      also in agreement with reaction-force analyses.

PMID- 20050638
TI  - Structure and energetics of C60O: a theoretical study.
AB  - Equilibrium structure geometries and stability of the epoxide [6,6] and open
      [5,6] isomers of C(60)O as well as rearrangement paths between the two isomers
      were determined using the second-order Moller-Plesset perturbation theory (MP2)
      and hybrid density functional theory (DFT, B3LYP and B3PW91) methods. It is
      manifested that the geometrical parameters involved in oxygen binding in C(60)O
      and relative stability between the [6,6] and [5,6] isomer of C(60)O have a strong
      dependence on basis set and electron correlation treatment, and it is important
      to employ an appropriate basis set and correlation level to correctly predict the
      equilibrium geometries and stability of the [6,6] and [5,6] isomers of C(60)O.
      For large enough basis sets at proper correlated levels such as the MP2 and
      B3PW91 DFT methods, the [6,6] isomer is found to be more stable than the [5,6]
      isomer, in contrast to previous semiempirical and low-level ab initio studies.
      The stability of the [6,6] form over the [5,6] form also appears to be derived
      from the difference in vibrational motions between the two isomers. It is also
      found that there appears to exist only one transition state connecting the two
      isomers, and rearrangement from the [6,6] isomer to the [5,6] isomer occurs via
      this transition state in a single step, although the barrier height appears to be
      rather high. A comparison of the simulated IR absorption spectra of the [6,6] and
      [5,6] form at the B3PW91/cc-pVDZ level with the experimental spectrum of C(60)O
      appears to suggest the presence and near-isoenergeticity of the [6,6] and [5,6]
      isomer of C(60)O at low temperature, in accordance with the calculation results
      reported in this paper.

PMID- 20050639
TI  - Template-directed molecular assembly on silicon carbide nanomesh: comparison
      between CuPc and pentacene.
AB  - The template-directed assembly of two planar molecules (copper phthalocyanine
      (CuPc) and pentacene) on SiC nanomesh has been studied by scanning tunneling
      microscopy and photoelectron spectroscopy, respectively. Both molecules are
      trapped as single molecules in the cells of SiC nanomesh at low coverage. At high
      coverage, CuPc forms a highly ordered single-molecular array with identical
      symmetry and periodicity as the substrate, whereas pentacene forms a quasi
      amorphous layer due to the random mixture of three different adsorption
      configurations. This difference in adsorption behavior is attributed to
      differences in molecular geometries. The measured changes of work functions
      reveal weak charge transfer between the molecules and substrate. Both molecules
      are preferentially adsorbed on the SiC nanomesh rather than on graphene. The CuPc
      single-molecular array possesses good long-range order, large area coverage, and
      a molecular density of over 3.0 x 10(13) molecules/cm(2).

PMID- 20050640
TI  - Highly uniform 300 mm wafer-scale deposition of single and multilayered
      chemically derived graphene thin films.
AB  - The deposition of atomically thin highly uniform chemically derived graphene
      (CDG) films on 300 mm SiO(2)/Si wafers is reported. We demonstrate that the very
      thin films can be lifted off to form uniform membranes that can be free-standing
      or transferred onto any substrate. Detailed maps of thickness using Raman
      spectroscopy and atomic force microscopy height profiles reveal that the film
      thickness is very uniform and highly controllable, ranging from 1-2 layers up to
      30 layers. After reduction using a variety of methods, the CDG films are
      transparent and electrically active with FET devices yielding high mobilities of
      approximately 15 cm(2)/(V s) and sheet resistance of approximately 1 kOmega/sq at
      approximately 70% transparency.

PMID- 20050641
TI  - Luminescence oxygen sensor based on a ruthenium(II) star polymer complex.
AB  - A novel quenchometric oxygen sensor based on a low polydispersity (PDI) star
      polymer [Ru(bpyPS(2))(3)](PF(6))(2) (bpy = 2,2'-bipyridine, PS = polystyrene) is
      reported. The synthesis, characterization, photophysics, and oxygen sensing
      properties are examined. Combining the polystyrene support with the oxygen
      sensing ruthenium complex provides much higher doping levels without
      microcrystallization of the complex than traditional two-component sensors. The
      single molecule approach also avoids sensor leaching. While the polydispersity
      was 1.10, indicating a very tight distribution of molecular weights, sensor
      heterogeneity was not completely eliminated, as the luminescence decays were
      still multiexponentials. The likely source of this heterogeneity and possible
      methods for generating more homogeneous materials are discussed.

PMID- 20050642
TI  - Degradation of glass artifacts: application of modern surface analytical
      techniques.
AB  - A detailed understanding of the stability of glasses toward liquid or atmospheric
      attack is of considerable importance for preserving numerous objects of our
      cultural heritage. Glasses produced in the ancient periods (Egyptian, Greek, or
      Roman glasses), as well as modern glass, can be classified as soda-lime-silica
      glasses. In contrast, potash was used as a flux in medieval Northern Europe for
      the production of window panes for churches and cathedrals. The particular
      chemical composition of these potash-lime-silica glasses (low in silica and rich
      in alkali and alkaline earth components), in combination with increased levels of
      acidifying gases (such as SO(2), CO(2), NO(x), or O(3)) and airborne particulate
      matter in today's urban or industrial atmospheres, has resulted in severe
      degradation of important cultural relics, particularly over the last century.
      Rapid developments in the fields of microelectronics and computer sciences,
      however, have contributed to the development of a variety of nondestructive,
      surface analytical techniques for the scientific investigation and material
      characterization of these unique and valuable objects. These methods include
      scanning electron microscopy in combination with energy- or wavelength-dispersive
      spectrometry (SEM/EDX or SEM/WDX), secondary ion mass spectrometry (SIMS), and
      atomic force microscopy (AFM). In this Account, we address glass analysis and
      weathering mechanisms, exploring the possibilities (and limitations) of modern
      analytical techniques. Corrosion by liquid substances is well investigated in the
      glass literature. In a tremendous number of case studies, the basic reaction
      between aqueous solutions and the glass surfaces was identified as an ion
      exchange reaction between hydrogen-bearing species of the attacking liquid and
      the alkali and alkaline earth ions in the glass, causing a depletion of the
      latter in the outermost surface layers. Although mechanistic analogies to liquid
      corrosion are obvious, atmospheric attack on glass ("weathering") is much more
      complex due to the multiphase system (atmosphere, water film, glass surface, and
      bulk glass) and added complexities (such as relative humidity and atmospheric
      pollutant concentration). Weathered medieval stained glass objects, as well as
      artifacts under controlled museum conditions, typically have less transparent or
      translucent surfaces, often with a thick weathering crust on top, consisting of
      sulfates of the glass constituents K, Ca, Na, or Mg. In this Account, we try to
      answer questions about glass analysis and weathering in three main categories.
      (i) Which chemical reactions are involved in the weathering of glass surfaces?
      (ii) Which internal factors (such as the glass composition or surface properties)
      play a dominant role for the weathering process? Can certain environmental or
      climatic factors be identified as more harmful for glasses than others? Is it
      possible to set up a quantitative relationship or at least an approximation
      between the degree of weathering and the factors described above? (iii) What are
      the consequences for the restoration and conservation strategies of endangered
      glass objects? How can a severe threat to precious glass objects be avoided, or
      at least minimized, to preserve these artifacts of our cultural heritage for
      future generations?

PMID- 20050643
TI  - Prediction of the basicities of pyridines in the gas phase and in aqueous
      solution.
AB  - The basicities of 125 pyridine derivatives in the gas phase and in water have
      been correlated with the electron density properties within the framework of
      quantum topological molecular similarity (QTMS). We used the theory of quantum
      chemical topology (QCT) to provide ab initio descriptors that are able to predict
      pK(b) values. Partial least squares (PLS) and the machine-learning technique
      Kriging generated validated models. Properties were considered for systems in
      their neutral and protonated forms. The compounds were divided into a training
      set, used to develop the models, and a test set, for which the predicted values
      of the different models were compared with the experimental ones. The results
      were found to be good for those compounds with substituents in the meta and para
      positions, whereas the use of Kriging was required to obtain reasonable results
      when ortho derivatives were included. The basicity was found to be better
      described in the gas phase than in water. Special attention was paid to external
      validation.

PMID- 20050644
TI  - Density functional investigation of structure and stability of Ge(n) and Ge(n)Ni
      (n = 1-20) clusters: validity of the electron counting rule.
AB  - Structure and electronic properties of neutral and cationic pure and Ni-doped Ge
      clusters containing 1-20 Ge atoms are calculated within the framework of linear
      combination of atomic orbitals density functional theory. It is found that in
      clusters containing more than 8 Ge atoms the Ni atom is absorbed endohedrally in
      the Ge cage. Relative stability of Ni-doped clusters at different sizes is
      studied by calculating their binding energy, embedding energy of a Ni atom in a
      Ge cluster, highest-occupied molecular orbital to lowest-unoccupied molecular
      orbital gap, and the second-order energy difference. Clusters having 20 valence
      electrons turn out to be relatively more stable in both the neutral and the
      cationic series. There is, infact, a sharp drop in IP as the valence electron
      count increases from 20 to 21, in agreement with predictions of shell models.
      Relevance of these results to the designing of Ge-based superatoms is discussed.

PMID- 20050645
TI  - Gas-phase structures of iron trihalides: a computational study of all iron
      trihalides and an electron diffraction study of iron trichloride.
AB  - The molecular structures of the monomers and dimers of all iron trihalides,
      FeF(3), FeCl(3), FeBr(3), and FeI(3), were determined by computations, and the
      structure of iron trichloride monomers and dimers was determined also by gas
      phase electron diffraction. The thermal-average bond length, r(g), of FeCl(3) is
      2.136(5) A, and the estimated equilibrium bond length from experiment, 2.122(6)
      A, is in excellent agreement with the computed value. Vibrational and
      thermodynamic properties have also been calculated for all species. The stability
      of iron trihalides decreases toward the iodide; neither the bromide nor the
      iodide can be evaporated without decomposition. The structures of isomers of
      trimers and tetramers for iron trichloride have also been calculated. The
      connection between the gas-phase and crystal-phase structures and the exceptional
      stability of the dimer is discussed.

PMID- 20050646
TI  - Polarity-sensitive coumarins tailored to live cell imaging.
AB  - Polarity-dependent fluorescent probes are recently attracting interest for high
      resolution cell imaging. Following a stepwise rational approach, we prepared and
      tested a toolbox of new coumarin derivatives tailored to in vivo imaging
      applications. Our compounds are characterized by a donor-(coumarin core)-acceptor
      molecular structure, where the electron donor is represented by alkylether or
      naphthyl groups, and the electron acceptor is represented by benzothiazene and
      cyano groups. Prior to synthesis, the substitution patterns were screened by
      computational methods to provide functional fluorescent derivatives easy to
      synthesize, and with excitation in the visible region of spectrum. We set up a
      robust synthetic procedure tunable on the substitution patterns to achieve. These
      coumarins possess excellent fluorescence quantum yields (up to 0.95), high molar
      extinction coefficients (up to 46,000 M(-1) cm(-1)), and large Stokes shifts.
      Furthermore, they display strong solvatochromism, being almost non-emissive in
      water and very fluorescent in less polar media (up to 780-fold enhancement in
      brightness). The solvatochromism of these compounds can be accounted for by a
      photophysical method encompassing two communicating excited states. When tested
      on cultured cells, the results showed that the developed coumarins were not
      harmful and their photophysical properties were unchanged compared to free
      solution. According to the determined solvatochromic properties, the coumarin
      fluorescence was detected only in the most lipophilic environments of the cell.
      The prepared compounds represent remarkable tools to investigate subtle
      biochemical processes in the cell environment after appropriate conjugation to
      biomolecules, and at the same time constitute the basis for further engineering
      of a new generation of biosensors.

PMID- 20050647
TI  - Homogeneous gold-catalyzed oxidative carboheterofunctionalization of alkenes.
AB  - Homogeneous carboamination, carboalkoxylation and carbolactonization of terminal
      alkenes are realized via oxidative gold catalysis, providing expedient access to
      various substituted N- or O-heterocycles. Deuterium-labeling studies established
      the anti nature of the alkene functionalization and the indispensible role of
      Au(I)/Au(III) catalysis. This study constitutes the first example of
      catalytically converting C(sp(3))-Au bonds into C(sp(3))--C(sp(2)) bonds in a
      cross-coupling manner and opens new opportunities to study gold alkene catalysis
      where alkylgold intermediates can be readily functionalized intermolecularly.

PMID- 20050648
TI  - Switching single azopyridine supramolecules in ordered arrays on Au(111).
AB  - 4,4-Azopyridine trimers and 4-phenylazopyridine dimers have been reversibly
      switched in ordered arrays on Au(111). During the switching process, single weak
      C-H...N hydrogen bonds are broken and reformed.

PMID- 20050649
TI  - Polymer glass transitions switch electron transfer in individual molecules.
AB  - Essentially complete photoinduced electron transfer quenching of the fluorescence
      of a perylene-calixarene compound occurs in poly(methyl acrylate) and poly(vinyl
      acetate) above their glass transition temperatures (T(g)), but the fluorescence
      is completely recovered upon cooling the polymer matrix to a few degrees below
      the T(g). The switching can be observed in an on/off fashion at the level of
      individual molecules.

PMID- 20050650
TI  - Rapid intramolecular hole hopping in meso-meso and meta-phenylene linked linear
      and cyclic multiporphyrin arrays.
AB  - A series of zinc porphyrin arrays comprised of a meso-meso linked porphyrin
      dimer, a meta-phenylene linked dimer, gable-like tetramers consisting of the meso
      meso linked dimers bridged via a meta-phenylene linker, and a dodecameric ring
      composed of this alternating dimeric pattern were singly oxidized, and
      intramolecular hole hopping between the porphyrin moieties was probed using
      electron paramagnetic resonance (EPR) spectroscopy. Electron nuclear double
      resonance (ENDOR) spectroscopy was also used to probe hole hopping within the
      dimers. Rapid hole hopping occurs between both porphyrins within both dimers and
      among three porphyrins of the tetramers with rates >10(7) s(-1) at 290 K.
      Additionally, the hole hops among 8-12 porphyrins in the dodecameric ring with a
      rate that is >10(7) s(-1) at 290 K, but hopping is slow at 180 K. These results
      show that hole hopping is rapid even though the meta-phenyl bridges and direct
      meso-meso linkages do not provide optimal electronic coupling between the
      porphyrins within these multiporphyrin arrays. This greatly expands the scope of
      possible structures that can be employed to tailor the design of long distance
      charge transport systems.

PMID- 20050651
TI  - Nickel/bis(oxazoline)-catalyzed asymmetric Kumada reactions of alkyl
      electrophiles: cross-couplings of racemic alpha-bromoketones.
AB  - The first asymmetric Kumada reactions of alkyl electrophiles are described,
      specifically, cross-couplings of racemic alpha-bromoketones with aryl Grignard
      reagents. Several features of this investigation are of interest. First, the
      couplings proceed at remarkably low temperature (-40 or -60 degrees C), which
      enables the asymmetric synthesis of racemization-prone alpha-arylketones. Second,
      dialkyl ketones undergo enantioselective coupling in good ee and yield. Third,
      readily available bis(oxazolines) are shown for the first time to be effective
      ligands for cross-couplings of alkyl electrophiles, thereby opening the door to
      new opportunities in asymmetric catalysis.

PMID- 20050652
TI  - Bioavailability of nanoscale metal oxides TiO(2), CeO(2), and ZnO to fish.
AB  - Nanoparticles (NPs) are reported to be a potential environmental health hazard.
      For organisms living in the aquatic environment, there is uncertainty on exposure
      because of a lack of understanding and data regarding the fate, behavior, and
      bioavailability of the nanomaterials in the water column. This paper reports on a
      series of integrative biological and physicochemical studies on the uptake of
      unmodified commercial nanoscale metal oxides, zinc oxide (ZnO), cerium dioxide
      (CeO(2)), and titanium dioxide (TiO(2)), from the water and diet to determine
      their potential ecotoxicological impacts on fish as a function of concentration.
      Particle characterizations were performed and tissue concentrations were measured
      by a wide range of analytical methods. Definitive uptake from the water column
      and localization of TiO(2) NPs in gills was demonstrated for the first time by
      use of coherent anti-Stokes Raman scattering (CARS) microscopy. Significant
      uptake of nanomaterials was found only for cerium in the liver of zebrafish
      exposed via the water and ionic titanium in the gut of trout exposed via the
      diet. For the aqueous exposures undertaken, formation of large NP aggregates (up
      to 3 mum) occurred and it is likely that this resulted in limited bioavailability
      of the unmodified metal oxide NPs in fish.

PMID- 20050653
TI  - High-precision measurement of isotope effects on noncovalent host-guest
      interactions.
AB  - The self-assembled supramolecular host [Ga(4)L(6)](12-) can bind cationic guest
      molecules to both the interior and exterior of the host assembly through
      noncovalent interactions. Very small equilibrium isotope effects (EIEs) have been
      precisely measured for the association of benzyltrimethylphosphonium
      isotopologues to the host exterior surface by adapting an NMR titration method
      originally developed by the Perrin group for measuring isotope effects on acidity
      constants. Deuteration of the phosphonium methyl groups was found to have a
      larger EIE than deuteration at the ring and benzyl positions, suggesting subtle
      differences in the noncovalent interactions between the host exterior and
      different guest C-H/D bonds. The application of this method to the measurement of
      EIEs on noncovalent host-guest interactions demonstrates the generality of this
      NMR technique in precisely measuring relative equilibrium constants.

PMID- 20050654
TI  - Transformation products in the life cycle impact assessment of chemicals.
AB  - The current life cycle impact assessment (LCIA) of chemicals focuses only on the
      fate and effects of the parent compound, neglecting the potential impact of
      transformation products. Here, we assess the importance of including the
      potential impact of transformation products in the calculation of
      characterization factors (CF). The developed method is applied to freshwater
      ecotoxicity for 15 pesticides and perchloroethylene, which are all known to have
      potentially persistent transformation products. The inclusion of transformation
      products resulted in a median increase in CF that varied from negligible to more
      than 5 orders of magnitude. This increase, however, can be highly uncertain,
      particularly due to a lack of toxicity data for transformation products and a
      lack of mode of action-specific data. We show in a case study that replacement of
      atrazine with other pesticides for application on corn results in a median impact
      score of 2 orders of magnitude lower when the fate and effects of only the parent
      compounds are included. When transformation products are included, the reduction
      in median impact score would likely be lower (less than 1 order of magnitude). An
      uncertainty analysis showed that the difference in impact scores of atrazine and
      the atrazine replacements was not statistically significant when only the parent
      chemical was considered. When transformation products were included, the
      uncertainty in impact scores was even greater.

PMID- 20050655
TI  - Highly enantioselective intramolecular copper catalyzed C-H insertion reactions
      of alpha-diazosulfones.
AB  - Excellent enantiocontrol (up to 98% ee) is achieved in copper catalyzed C-H
      insertions of alpha-diazosulfones to form thiopyrans, with up to 60% ee in C-H
      insertions leading to sulfolanes.

PMID- 20050656
TI  - Spectroscopic identification of ternary Cm-carbonate surface complexes.
AB  - The influence of dissolved CO(2) on the sorption of trivalent curium (Cm) on
      alumina (gamma-Al(2)O(3)) and kaolinite was investigated by time resolved laser
      fluorescence spectroscopy (TRLFS) using the optical properties of Cm as a local
      luminescent probe. Measurements were performed at T < 20 K on Cm loaded gamma
      Al(2)O(3) and kaolinite wet pastes prepared in the absence and presence of
      carbonate in order to pictorially illustrate any changes through a direct
      comparison of spectra from both systems. The red-shift of excitation and emission
      spectra, as well as the increase of fluorescence lifetimes observed in the
      samples with carbonate, clearly showed the influence of carbonate and was fully
      consistent with the formation of Cm(III) surface species involving carbonate
      complexes. In addition, the biexponential decay behavior of the fluorescence
      lifetime indicated that at least two different Cm(III)-carbonate species exist at
      the mineral-water interface. These results provide the first spectroscopic
      evidence for the formation of ternary Cm(III)-carbonate surface complexes.

PMID- 20050657
TI  - Curvature sensing by the epsin N-terminal homology domain measured on cylindrical
      lipid membrane tethers.
AB  - The protein epsin is believed to play important roles in clathrin-mediated
      endocytosis, including generation of the high membrane curvature necessary for
      vesicle formation. Here we assess the basis for this hypothesis by systematically
      quantifying the curvature dependence of the area density of epsin N-terminal
      homology (ENTH) domain on cylindrical membranes of controlled curvature. In
      cylindrical tethers pulled from micropipet-aspirated giant unilamellar vesicles,
      repartitioning of membrane-bound ENTH from vesicles onto highly curved membranes
      was observed by fluorescence microscopy. First-order thermodynamic theory used to
      analyze our data yielded the first measurement of Leibler's thermodynamic
      curvature-composition coupling coefficient to be reported for an endocytic
      accessory protein. Our results highlight the possibility that epsin contributes
      to cellular membrane curvature sensing and generation, and we believe that our
      method will provide useful contributions toward the goal of relating molecular
      descriptions of interactions to macroscopic membrane remodeling in cells and
      identifying and characterizing roles for proteins in these processes.

PMID- 20050658
TI  - Combined single-molecule photon-stamping spectroscopy and femtosecond transient
      absorption spectroscopy studies of interfacial electron transfer dynamics.
AB  - The inhomogeneous interfacial electron transfer (IET) dynamics of 9-phenyl-2,3,7
      trihydroxy-6-fluorone (PF)-sensitized TiO(2) nanoparticles (NPs) has been probed
      by a single-molecule photon-stamping technique as well as ensemble-averaged
      femtosecond transient absorption spectroscopy. The forward electron transfer
      (FET) time shows a broad distribution at the single-molecule level, indicating
      the inhomogeneous interactions and ET reactivity of the PF/TiO(2) NP system. The
      broad distribution of the FET time is measured to be 0.4 +/- 0.1 ps in the
      transient absorption and picoseconds to nanoseconds in the photon-stamping
      measurements. The charge recombination time, having a broad distribution at the
      single-molecule level, clearly shows a biexponential dynamic behavior in the
      transient absorption: a fast component of 3.0 +/- 0.1 ps and a slow component of
      11.5 +/- 0.5 ns. We suggest that both strong and weak interactions between PF and
      TiO(2) coexist, and we have proposed two mechanisms to interpret the observed IET
      dynamics. A single-molecule photon-stamping technique and ensemble-averaged
      transient absorption spectroscopy provide efficient "zoom-in" and "zoom-out"
      approaches for probing the IET dynamics. The physical nature of the observed
      multiexponential or stretched-exponential ET dynamics in the ensemble-averaged
      experiments, often associated with dynamic and static inhomogeneous ET dynamics,
      can be identified and analyzed by single-molecule spectroscopy measurements.

PMID- 20050659
TI  - Carbon dioxide emission implications if hydrofluorocarbons are regulated: a
      refrigeration case study.
AB  - The U.S. is strongly considering regulating hydrofluorocarbons (HFCs) due to
      their global climate change forcing effects. A drop-in replacement
      hydrofluoroether has been evaluated using a gate-to-grave life cycle assessment
      of greenhouse gas emissions for the trade-offs between direct and indirect carbon
      dioxide equivalent emissions compared to a current HFC and a historically used
      refrigerant. The results indicate current regulations being considered may
      increase global climate change.

PMID- 20050660
TI  - Replacing Mn(2+) with Co(2+) in human arginase i enhances cytotoxicity toward l
      arginine auxotrophic cancer cell lines.
AB  - Replacing the two Mn(2+) ions normally present in human Arginase I with Co(2+)
      resulted in a significantly lowered K(M) value without a concomitant reduction in
      k(cat). In addition, the pH dependence of the reaction was shifted from a pK(a)
      of 8.5 to a pK(a) of 7.5. The combination of these effects led to a 10-fold
      increase in overall catalytic activity (k(cat)/K(M)) at pH 7.4, close to the pH
      of human serum. Just as important for therapeutic applications, Co(2+)
      substitution lead to significantly increased serum stability of the enzyme. Our
      data can be explained by direct coordination of l-Arg to one of the Co(2+) ions
      during reaction, consistent with previously reported model studies. In vitro
      cytotoxicity experiments verified that the Co(2+)-substituted human Arg I
      displays an approximately 12- to 15-fold lower IC(50) value for the killing of
      human hepatocellular carcinoma and melanoma cell lines and thus constitutes a
      promising new candidate for the treatment of l-Arg auxotrophic tumors.

PMID- 20050661
TI  - Influence of staged-air on airflow, combustion characteristics and NO(x)
      emissions of a down-fired pulverized-coal 300 MW(e) utility boiler with direct
      flow split burners.
AB  - Cold airflow experiments were conducted to investigate the aerodynamic field in a
      small-scale furnace of a down-fired pulverized-coal 300 MW(e) utility boiler
      arranged with direct flow split burners enriched by cyclones. By increasing the
      staged-air ratio, a deflected flow field appeared in the lower furnace; larger
      staged-air ratios produced larger deflections. Industrial-sized experiments on a
      full-scale boiler were also performed at different staged-air damper openings
      with measurements taken of gas temperatures in the burner region and near the
      right-side wall, wall heat fluxes, and gas components (O(2), CO, and NO(x)) in
      the near-wall region. Combustion was unstable at staged-air damper openings below
      30%. For openings of 30% and 40%, late ignition of the pulverized coal developed
      and large differences arose in gas temperatures and heat fluxes between the
      regions near the front and rear walls. In conjunction, carbon content in the fly
      ash was high and boiler efficiency was low with high NO(x) emission above 1200
      mg/m(3) (at 6% O(2) dry). For fully open dampers, differences in gas temperatures
      and heat fluxes, carbon in fly ash and NO(x) emission decreased yielding an
      increase in boiler efficiency. The optimal setting is fully open staged-air
      dampers.

PMID- 20050662
TI  - Thallium as a tracer for preindustrial volcanic eruptions in an ice core record
      from Illimani, Bolivia.
AB  - Trace element records from glacier and ice sheet archives provide insights into
      biogeochemical cycles, atmospheric circulation changes, and anthropogenic
      pollution history. We present the first continuous high-resolution thallium (Tl)
      record, derived from an accurately dated ice core from tropical South America,
      and discuss Tl as a tracer for volcanic eruptions. We identify four prominent Tl
      peaks and propose that they represent signals from the massive explosive
      eruptions of the "unknown 1258" A.D. volcano, of Kuwae ( approximately 1450
      A.D.), Tambora (1815 A.D.), and Krakatoa (1883 A.D.). The highly resolved record
      was obtained with an improved setup for the continuous analysis of trace elements
      in ice with inductively coupled plasma sector field mass spectrometry (ICP-SFMS).
      The new setup allowed for a stronger initial acidification of the meltwater and
      shorter tubing length, thereby reducing the risk of memory effects and losses of
      analytes to the capillary walls. With a comparison of the continuous method to
      the established conventional decontamination and analysis procedure for discrete
      samples, we demonstrate the accuracy of the continuous method for Tl analyses.

PMID- 20050663
TI  - Drying affects artemisinin, dihydroartemisinic acid, artemisinic acid, and the
      antioxidant capacity of Artemisia annua L. leaves.
AB  - There is limited information on how postharvest drying of Artemisia annua affects
      artemisinin (ART) biosynthesis and A. annua antioxidant capacity. Antioxidants
      may boost the bioactivity of ART and the crop commercial value. We evaluated the
      effect of freeze, oven, shade, and sun drying, time of drying, and light
      intensity on the leaf concentration of ART, dihydroartemisinic acid (DHAA),
      artemisinic acid (AA), and on the leaf antioxidant capacity. Freeze-dried samples
      had the lowest ART concentrations as compared to the other drying methods.
      However, the ferric reducing antioxidant power assay showed that freeze- and oven
      dried samples had similarly high antioxidant activities, which declined
      significantly after plants were shade- and sun-dried. Shade drying for 1, 2, and
      3 weeks, under ambient or low light, did not change the ART content but
      significantly decreased the leaf antioxidant activity, mainly if sun-dried. A
      significant decrease (82% average) in DHAA was observed for all drying procedures
      as compared to freeze drying, with a simultaneous, significant increase in ART
      (33% average). The average bioconversion of DHAA to ART was 43% for oven- and
      shade-dried plants and 94% for sun-dried plants, reiterating the hypothesis that
      DHAA, not AA, is the main biosynthetic precursor of ART and suggesting that sun
      drying improves the bioconversion from DHAA to ART. Data also indicate that oven
      drying for 24 h at 45 degrees C can provide good levels of both ART and
      antioxidants in leaves. These findings are valuable for the commercial production
      of ART and of bioactive antioxidants that might synergize with the antimalarial
      and anticancer effects of ART when combined in traditional preparations to
      improve human and animal health.

PMID- 20050664
TI  - Changes in arterial blood pressure of a soluble cocoa fiber product in
      spontaneously hypertensive rats.
AB  - The effect produced by long-term intake of a soluble cocoa fiber product (SCFP)
      on the development of hypertension of spontaneously hypertensive rats (SHR) was
      evaluated. Twenty male 3-week-old SHR were divided into two groups of 10 animals
      that drank either tap water (control) or a solution of SCFP (0.75 g/day SCFP)
      until the 20th week of life. Five 20-week-old rats of each group were sacrificed.
      Tap water as drinking fluid was given to all the animals from the 20th to 24th
      week of life. The 24-week-old rats were also sacrificed. Body weight, liquid and
      dry food intake, and arterial blood pressure (tail cuff) were recorded weekly.
      Malondialdehyde (MDA), glucose and angiotensin converting enzyme (ACE) activity
      in the plasma from the sacrificed rats were also obtained, and we evaluated the
      relaxation caused by acetylcholine in the aorta from these animals. SCFP
      attenuated the development of hypertension in SHR; however, the withdrawal of
      SCFP caused an increase in blood pressure in the rats. Body weight gain was
      slower in the group treated with SCFP. SCFP increased liquid intake but decreased
      dry food intake in the rats. SCFP decreased plasma MDA concentrations and
      slightly decreased plasma ACE activity, but no differences were observed in
      plasma glucose and in the aorta responses to acetylcholine in both groups of 20
      week-old SHR. We have demonstrated the antihypertensive and antioxidant
      properties of SCFP. The control of body weight and the control of increased
      angiotensin II may be involved in the antihypertensive effect of this product.

PMID- 20050665
TI  - Human urine and wood ash as plant nutrients for red beet (Beta vulgaris)
      cultivation: impacts on yield quality.
AB  - The objective of this study was to evaluate the effect of human urine and wood
      ash fertilization on the yield and quality of red beet by measuring the
      microbial, nutrient, and antioxidant (betanin) content of the roots. Red beets
      were fertilized with 133 kg of N/ha as mineral fertilizer, urine and ash, and
      only urine with no fertilizer as a control. The mineral-fertilized plants and
      urine- and ash-fertilized plants also received 89 kg of P/ha. Urine and ash and
      only urine fertilizer produced 1720 and 656 kg/ha more root biomass,
      respectively, versus what was obtained from the mineral fertilizer. Few fecal
      coliforms and coliphage were detected in mineral-fertilized and urine- and ash
      fertilized red beet roots. The protein and betanin contents in red beet roots
      were similar in all treatments. In conclusion, this study revealed that urine
      with or without ash can increase the yield of red beet and furthermore the
      microbial quality and chemical quality were similar to the situation in mineral
      fertilized products.

PMID- 20050666
TI  - Primary study on mode of action for macrocyclic fungicide candidates (7B3, D1)
      against Rhizoctonia solani Kuhn.
AB  - A novel macrolactam fungicide candidate (7B3) and a novel aza-macrolactone
      fungicide candidate (D1) were designed and synthesized, and the bioassay showed
      that both displayed excellent fungicidal activity against Rhizoctonia solani
      Kuhn. To elucidate the biochemical mode of action of the two compounds against R.
      solani and illustrate the similarities and differences of action mechanism
      resulting from subtle differences in structure of the two compounds, the effects
      of the two compounds on the ultrastructure of hyphae, electrolyte leakage, and
      respiration of mycelia cell suspension caused by 7B3 or D1 were studied. The
      results showed that the two compounds had very similar modes of action. Both
      induced irregular swelling of hyphae, vacuolation of cytoplasm, and thickening of
      cell wall. The conductivity of mycelia cell suspension increased in the presence
      of 7B3 or D1, which indicated that the two compounds had a similar effect on cell
      membrane permeability. In addition, both 7B3 and D1 were insufficient in
      inhibiting the respiration of mycelia.

PMID- 20050667
TI  - Degradation of 4-nitrophenol, 2-chloro-4-nitrophenol, and 2,4-dinitrophenol by
      Rhodococcus imtechensis strain RKJ300.
AB  - A bacterial strain Rhodococcus imtechensis RKJ300 (= MTCC 7085(T) = JCM 13270(T))
      was isolated from pesticide-contaminated soil of Punjab by the enrichment
      technique on minimal medium containing 4-nitrophenol. Strain RKJ300 is capable of
      utilizing 4-nitrophenol, 2-chloro-4-nitrophenol, and 2,4-dinitrophenol as sole
      sources of carbon and energy. The strain involved both oxidative and reductive
      catabolic mechanisms for initial transformation of these compounds. In the case
      of 2-chloro-4-nitrophenol, colorimetric analysis indicated that nitrite release
      was followed by stoichiometric elimination of chloride ions. Experiments using
      whole cells and cell-free extracts showed chlorohydroquinone and hydroquinone as
      the intermediates of 2-chloro-4-nitrophenol degradation. This is the first report
      of degradation on 2-chloro-4-nitrophenol by a bacterium under aerobic condition
      to the best of our knowledge. However, pathways for degradation of 4-nitrophenol
      and 2,4-dinitrophenol were similar to those reported in other strains of
      Rhodococcus. Laboratory-scale soil microcosm studies demonstrated that the
      organism was capable of degrading a mixture of nitrophenols simultaneously,
      indicating its applicability toward in situ bioremediation of contaminated sites.
      The fate of the augmented strain as monitored by the plate-counting method and
      hybridization technique was found to be fairly stable throughout the period of
      microcosm experiments.

PMID- 20050668
TI  - Cationic amphiphile with shikimic acid headgroup shows more systemic promise than
      its mannosyl analogue as DNA vaccine carrier in dendritic cell based genetic
      immunization.
AB  - Mannosylated cationic vectors have been previously used for delivering DNA
      vaccines to antigen presenting cells (APCs) via mannose receptors expressed on
      the cell surface of APCs. Here we show that cationic amphiphiles containing
      mannose-mimicking quinic acid and shikimic acid headgroups deliver genes to APCs
      via mannose receptor. Cationic amphiphile with shikimic acid headgroup was more
      efficacious than its mannosyl counterpart in combating mouse tumor growth by
      dendritic cell (the most professional APC) based genetic immunization.

PMID- 20050669
TI  - Discovery of (thienopyrimidin-2-yl)aminopyrimidines as potent, selective, and
      orally available pan-PI3-kinase and dual pan-PI3-kinase/mTOR inhibitors for the
      treatment of cancer.
AB  - The PI3K/AKT/mTOR pathway has been shown to play an important role in cancer.
      Starting with compounds 1 and 2 (GDC-0941) as templates, (thienopyrimidin-2
      yl)aminopyrimidines were discovered as potent inhibitors of PI3K or both PI3K and
      mTOR. Structural information derived from PI3K gamma-ligand cocrystal structures
      of 1 and 2 were used to design inhibitors that maintained potency for PI3K yet
      improved metabolic stability and oral bioavailability relative to 1. The addition
      of a single methyl group to the optimized 5 resulted in 21, which had
      significantly reduced potency for mTOR. The lead compounds 5 (GNE-493) and 21
      (GNE-490) have good pharmacokinetic (PK) parameters, are highly selective,
      demonstrate knock down of pathway markers in vivo, and are efficacious in
      xenograft models where the PI3K pathway is deregulated. Both compounds were
      compared in a PI3K alpha mutated MCF7.1 xenograft model and were found to have
      equivalent efficacy when normalized for exposure.

PMID- 20050670
TI  - Rational design of targeted cancer therapeutics through the multiconjugation of
      folate and cleavable siRNA to RAFT-synthesized (HPMA-s-APMA) copolymers.
AB  - A well-defined N-(2-hydroxypropyl)methacrylamide-s-N-(3
      aminopropyl)methacrylamide (HPMA-s-APMA) copolymer, synthesized via reversible
      addition-fragmentation chain transfer (RAFT) polymerization, was utilized for the
      rational design of multiconjugates containing both a gene therapeutic, small
      interfering RNA (siRNA), and a cancer cell targeting moiety, folate. The
      copolymer contains a biocompatible poly(HPMA) portion (91 mol %) and a primary
      amine, APMA, portion (9 mol %). A fraction (20 mol %) of the APMA repeats were
      converted to activated thiols utilizing the amine- and sulfhydryl-reactive
      molecule N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP). 5'-Thiolated sense
      strand RNAs were then coupled to the polymer through a disulfide exchange with
      pendant pyridyldithio moieties, giving an 89 +/- 4% degree of conjugation. The
      unmodified APMA units (80 mol %) were subsequently coupled to amine reactive
      folates with 81 +/- 1% efficiency. This yielded a multiconjugate copolymer with
      91 mol % HPMA, 2 mol % RNA, and 6 mol % folate. siRNA formation was achieved by
      annealing antisense strands to the conjugated RNA sense strands. Subsequent siRNA
      cleavage under intracellular conditions demonstrated the potential utility of
      this carrier in gene delivery. The multiconjugate copolymer and siRNA release
      were characterized by UV-vis spectroscopy and polyacrylamide gel electrophoresis.

PMID- 20050671
TI  - Improvement of the hemocompatibility of PET surfaces using different sulphated
      polysaccharides as coating materials.
AB  - In this study, sulphated polysaccharides were investigated in respect to their
      blood compatibility properties (hemocompatibility). Pure chitosan was treated
      with sulphating agents such as SO(3)/pyridine complex and chlorosulfonic acid
      (HClSO(3)) to obtain 3,6-O-sulfochitosan with low and high concentration of
      sulfur. These synthetically derived materials and the commercially available
      sulphated polysaccharides heparin and dextran sulfate, both with high
      concentrations of sulfur, were coated onto PET foils to act as surfaces with
      strong antithrombotic activity. This treatment should lead to better blood
      compatibility properties of PET materials for medical applications. To examine
      this, the optimized free hemoglobin method was applied to determine the
      antithrombotic activity of these surfaces. Glass as the standard thrombotic
      surface and a heparin-coated PET surface as a surface well-known for its strong
      antithrombotic activity were used as internal references. The experiments showed
      that dextran sulfate and sulphated chitosan with high concentrations of sulfur
      demonstrated the same antithrombotic activity as heparin over the whole period of
      measurement time. In addition, a relationship between the sulfur concentration in
      these sulphated polysaccharides and their blood compatibility properties can be
      demonstrated in this article.

PMID- 20050672
TI  - Highly suppressing wild-type HIV-1 and Y181C mutant HIV-1 strains by 10
      chloromethyl-11-demethyl-12-oxo-calanolide A with druggable profile.
AB  - We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A
      (20, EC(50) = 7.4 nM, SI = 1417), which demonstrates a druggable profile with
      32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice,
      and especially the feature of highly efficient suppression of the wild-type HIV-1
      and Y181C mutant HIV-1 at an EC(50) = 7.4 nM and EC(50) = 0.46 nM, respectively.

PMID- 20050673
TI  - Optical modes excited by evanescent-wave-coupled PbS nanocrystals in
      semiconductor microtube bottle resonators.
AB  - We report on optical modes in rolled-up microtube resonators that are excited by
      PbS nanocrystals filled into the microtube core. Long ranging evanescent fields
      into the very thin walled microtubes cause strong emission of the nanocrystals
      into the resonator modes and a mode shift after a self-removal of the solvent. We
      present a method to precisely control the number, the energy and the localization
      of the modes along the microtube axis.

PMID- 20050674
TI  - Nanoscale structural engineering via phase segregation: Au-Ge system.
AB  - A tunable structural engineering of nanowires based on template-assisted alloying
      and phase segregation processes is demonstrated. The Au-Ge system, which has a
      low eutectic temperature and negligible solid solubility (<10(-3) atom %) of Au
      in Ge at low temperatures, is utilized. Depending on the Au concentration of the
      initial nanowires, final structures ranging from nearly periodic nanodisk
      patterns to core/shell and fully alloyed nanowires are produced. The formation
      mechanisms are discussed in detail and characterized by in situ transmission
      electron microscopy and energy-dispersive spectrometry analyses. Electrical
      measurements illustrate the metallic and semiconducting characteristics of the
      fully alloyed and alternating Au/Ge nanodisk structures, respectively.

PMID- 20050675
TI  - Scaling properties in transistors that use aligned arrays of single-walled carbon
      nanotubes.
AB  - Recent studies and device demonstrations indicate that horizontally aligned
      arrays of linearly configured single-walled carbon nanotubes (SWNTs) can serve as
      an effective thin film semiconductor material, suitable for scalable use in high
      performance transistors. This paper presents the results of systematic
      investigations of the dependence of device properties on channel length, to
      reveal the role of channel and contact resistance in the operation. The results
      indicate that, for the range of channel lengths and SWNT diameters studied here,
      source and drain contacts of Pd yield transistors with effectively Ohmic contacts
      that exhibit negligible dependence of their resistances on gate voltage. For
      devices that use Au, modulation of the resistance of the contacts represents a
      significant contribution to the response. Extracted values of the mobilities of
      the semiconducting SWNTs and the contact resistances associated with metallic and
      semiconducting SWNTs are consistent with previous reports on single tube test
      structures.

PMID- 20050676
TI  - Direct force measurements on double-stranded RNA in solid-state nanopores.
AB  - Solid-state nanopores can be employed to detect and study local structure along
      single molecules by voltage driven translocation through the nanopore. Their
      sensitivity and versatility can be augmented by combining them with a direct
      force probe, for example, optical tweezers. Such a tool could potentially be used
      to directly probe RNA secondary structure through the sequential unfolding of
      duplex regions. Here, we demonstrate the first application of such a system to
      the study of RNA by directly measuring the net force on individual double
      stranded RNA (dsRNA) molecules. We have probed the force on dsRNA over a large
      range of nanopore sizes from 35 nm down to 3.5 nm and find that it decreases as
      the pore size is increased, in accordance with numerical calculations.
      Furthermore, we find that the force is independent of the distance between the
      optical trap and the nanopore surface, permitting force measurement on quite
      short molecules. By comparison with dsDNA molecules trapped in the same
      nanopores, we find that the force on dsRNA is on the order of, but slightly lower
      than, that on dsDNA. With these measurements, we expand the possibilities of the
      nanopore-optical tweezers to the study of RNA molecules with potential
      applications to the detection of RNA-bound proteins, the determination of RNA
      secondary structure, and the processing of RNA by molecular motors.

PMID- 20050677
TI  - Thermal expansion pump for capillary high-performance liquid chromatography.
AB  - A thermal expansion pump (TEP) based on a principle of liquid thermal expansion
      for capillary high-performance liquid chromatography has been developed. The
      novel pump is capable of generating a continuous flow at high pressure for
      constant and stable delivery of binary solvents from nanoliters to microliters
      per minute without splitting. Theoretical equations for controlling fluidic
      output of this pump have been established and validated by a series of
      experiments. Factors affecting flow rate, such as density discrepancy, liquid
      compressibility, and mass loss in output, were taken into account. An assembly of
      the pump system employing two groups of thermal expansion pumps (TEPs) working in
      turns were fabricated, and a controlling strategy for the pump system to maintain
      a continuous delivery without pressure fluctuation even at switching points was
      also developed. Both isocratic and gradients of binary solvent delivery by the
      TEPs were performed. Reproducibility and standard deviation at different flow
      rates were determined. A capillary high-performance liquid chromatography (micro
      HPLC) system consisting of the TEPs, an injection valve, a homemade packed
      capillary column (20 cm x 100 microm i.d. with 5 microm C18), and a laser-induced
      fluorescence detector was set up, and sample separations were carried out.
      Results of RSD = 4% for flow and RSD = 2% for retention times at 500 nL/min were
      achieved. Such a pump system has almost no moving parts except for the solvent
      switches. Its overall costs of manufacture and running are very low. It is proven
      that the TEPs system has great potential and competitive capabilities in
      capillary liquid chromatography.

PMID- 20050678
TI  - Simultaneous imaging of small metabolites and lipids in rat brain tissues at
      atmospheric pressure by laser ablation electrospray ionization mass spectrometry.
AB  - Atmospheric pressure imaging mass spectrometry is a rapidly expanding field that
      offers advantages in the ability to study biological systems in their native
      condition, simplified sample preparation, and high-throughput experiments. In
      laser ablation electrospray ionization (LAESI), the native water molecules in
      biological tissues facilitate sampling by a focused mid-infrared laser beam. The
      ionization of the ablated material is accomplished by electrospray
      postionization. In this work, we demonstrate that the imaging variant of LAESI
      simultaneously provides lateral distributions for small metabolites and lipids
      directly in rat brain sections. To cope with the fragile nature and potential
      dehydration of the brain tissue due to drying in the ambient environment as well
      as to minimize analyte redistribution, a Peltier cooling stage is integrated into
      the LAESI imaging system. We demonstrate the utility of high-resolution (m/Deltam
      > 6000) time-of-flight mass spectrometry with LAESI to deconvolute spatial
      distributions of different chemical species with identical nominal mass. To help
      with the evaluation of the massive data sets, Pearson colocalization maps are
      calculated for selected small metabolites and lipids. We show that this approach
      reveals biologically meaningful correlations between these two classes of
      biomolecules.

PMID- 20050679
TI  - Biophysical characterization of Abeta42 C-terminal fragments: inhibitors of
      Abeta42 neurotoxicity.
AB  - A key event in Alzheimer's disease (AD) is age-dependent, brain accumulation of
      amyloid beta-protein (Abeta) leading to Abeta self-association into neurotoxic
      oligomers. Previously, we showed that Abeta oligomerization and neurotoxicity
      could be inhibited by C-terminal fragments (CTFs) of Abeta42. Because these CTFs
      are highly hydrophobic, we asked if they themselves aggregated and, if so, what
      parameters regulated their aggregation. To answer these questions, we
      investigated the dependence of CTF aqueous solubility, aggregation kinetics, and
      morphology on peptide length and sequence and the correlation between these
      characteristics and inhibition of Abeta42-induced toxicity. We found that CTFs up
      to 8 residues long were soluble at concentrations >100 microM and had a low
      propensity to aggregate. Longer CTFs were soluble at approximately 1-80 microM,
      and most, but not all, readily formed beta-sheet-rich fibrils. Comparison to
      Abeta40-derived CTFs showed that the C-terminal dipeptide I41-A42 strongly
      promoted aggregation. Aggregation propensity correlated with the previously
      reported tendency to form beta-hairpin conformation but not with inhibition of
      Abeta42-induced neurotoxicity. The data enhance our understanding of the physical
      characteristics that affect CTF activity and advance our ability to design,
      synthesize, and test future generations of inhibitors.

PMID- 20050680
TI  - The Western Airborne Contaminant Assessment Project (WACAP): an interdisciplinary
      evaluation of the impacts of airborne contaminants in western U.S. National
      Parks.

PMID- 20050682
TI  - Comment on "brominated flame retardants in children's toys: concentration,
      composition, and children's exposure and risk assessment".

PMID- 20050684
TI  - Anti-tobacco mosaic virus (TMV) Quassinoids from Brucea javanica (L.) Merr.
AB  - Two new quassinoids, javanicolide E (1) and javanicolide F (2), along with
      fifteen known C-20 quassinoids were isolated from the seeds of Brucea javanica
      (L.) Merr. The antitobacco mosaic virus (TMV) activity of these quassinoids was
      screened by the conventional half-leaf and leaf-disk method along with Western
      blot analysis. All of the seventeen quassinoids showed potent anti-TMV activity.
      Among them, eight compounds, brusatol (3), bruceine B (4), bruceoside B (5),
      yadanzioside I (6), yadanzioside L (7), bruceine D (8), yadanziolide A (9), and
      aglycone of yadanziolide D (17), showed strong antiviral activities, with IC(50)
      values in the range of 3.42-5.66 microM, and were much more effective than the
      positive control, ningnanmycin (IC(50) = 117.3 microM). The antiviral structure
      activity relationships of quassinoids against TMV were also discussed.

PMID- 20050683
TI  - Degradation of soluble and fibrillar amyloid beta-protein by matrix
      metalloproteinase (MT1-MMP) in vitro.
AB  - The progressive accumulation of beta-amyloid (Abeta) in senile plaques and in the
      cerebral vasculature is the hallmark of Alzheimer's disease and related
      disorders. Degradation of Abeta by specific proteolytic enzymes is an important
      process that regulates its levels in brain. Matrix metalloproteinase 2 (MMP2) was
      shown to be expressed in reactive astrocytes surrounding amyloid plaques and may
      contribute to Abeta degradation. Membrane type 1 (MT1) MMP is the physiological
      activator for the zymogen pro-MMP2. Here, we show that, in addition to MMP2, its
      activator MT1-MMP is also expressed in reactive astrocytes in regions with
      amyloid deposits in transgenic mice. Using a Cos-1 cell expression system, we
      demonstrated that MT1-MMP can degrade exogenous Abeta40 and Abeta42. A purified
      soluble form of MT1-MMP degraded both soluble and fibrillar Abeta peptides in a
      time-dependent manner, yielding specific degradation products. Mass spectrometry
      analysis identified multiple MT1-MMP cleavage sites on soluble Abeta40 and
      Abeta42. MT1-MMP-mediated Abeta degradation was inhibited with the general MMP
      inhibitor GM6001 or the specific MT1-MMP inhibitor tissue inhibitor of
      metalloproteinases 2. Furthermore, in situ experiments showed that purified MT1
      MMP degraded parenchymal fibrillar amyloid plaques that form in the brains of
      Abeta precursor protein transgenic mice. Together, these findings indicate that
      MT1-MMP possesses Abeta degrading activity in vitro.

PMID- 20050685
TI  - Modulation of electron injection in CdSe-TiO(2) system through medium alkalinity.
AB  - Charge injection from excited CdSe quantum dots into nanostructured TiO(2) film
      can be modulated by varying solution pH. At increasing solution pH, the
      conduction band of TiO(2) shifts 59 mV/pH unit to a more negative potential,
      thereby decreasing the driving force and thus decreasing the rate of nonradiative
      electron transfer from excited CdSe. The emission yield and the average emission
      lifetime increase with increasing pH, thus providing a way to monitor the
      variation in medium pH.

PMID- 20050686
TI  - Origin of intense chiroptical effects in undecagold subnanometer particles.
AB  - Time-dependent density functional theory (TDDFT) calculations are employed to
      examine the optical absorption and circular dichroism (CD) spectra of undecagold
      Au(11)L(4)X(2)(+) (X = Cl, Br) complexes and their Au(2)X(2)L precursors, where L
      is either 2,2'-bis(diphenylphosphino)-1,1'-binaphtyl (BINAP) or 1,4-diphosphino
      1,3-butadiene (dpb). These systems exhibit intense and mirror-image Cotton
      effects in their CD spectra. Experimental peak positions are well reproduced in
      the calculations. The low energy peaks of Au(11)L(4)X(2)(+) arise primarily from
      transitions between delocalized metal superatom orbitals. Bidentate phosphine
      ligands have both a structural and electronic impact on the system. The lowest
      energy structure of Au(11)L(4)X(2)(+) has a chiral C(2) geometry, whereas
      monodentate phosphine ligands lead to a C(1) structure. In addition, the chiral
      core structure of Au(11)L(4)X(2)(+) is not sufficient to explain the strong
      Cotton effects, and the intensity of the CD spectrum is increased by the presence
      of the bidentate phosphine ligands.

PMID- 20050687
TI  - Unintended compositional changes in transgenic rice seeds ( Oryza sativa L.)
      studied by spectral and chromatographic analysis coupled with chemometrics
      methods.
AB  - Unintended compositional changes in transgenic rice seeds were studied by near
      infrared reflectance, GC-MS, HPLC, and ICP-AES coupled with chemometrics
      strategies. Three kinds of transgenic rice with resistance to fungal diseases or
      insect pests were comparatively studied with the nontransgenic counterparts in
      terms of key nutrients such as protein, amino acids, fatty acids, vitamins,
      elements, and antinutrient phytic acid recommended by the Organization for
      Economic Co-operation and Development (OECD). The compositional profiles were
      discriminated by chemometrics methods, and the discriminatory compounds were
      protein, three amino acids, two fatty acids, two vitamins, and several elements.
      Significance of differences for these compounds was proved by analysis of
      variance, and the variation extent ranged from 20 to 74% for amino acids, from 19
      to 38% for fatty acids, from 25 to 57% for vitamins, from 20 to 50% for elements,
      and 25% for protein, whereas phytic acid content did not change significantly.
      The unintended compositional alterations as well as unintended change of physical
      characteristic in transgenic rice compared with nontransgenic rice might be
      related to the genetic transformation, the effect of which needs to be elucidated
      by additional studies.

PMID- 20050689
TI  - Interfacial complexation explains anomalous diffusion in nanofluids.
AB  - A recent report describing dramatic anomalous enhancement in mass transport
      properties of nanofluids (>1000% increase in tracer dye diffusivity) has excited
      intense interest, but the findings have yet to be conclusively confirmed or
      explained. Here we investigate these phenomena using a microfluidic approach to
      directly probe tracer diffusion so that interactions between the suspension's
      principle components (nanoparticles, surfactant, and dye) can be clearly
      identified. Under conditions matching previously reported studies, we
      unexpectedly observe spontaneous formation of highly focused and intensely
      fluorescent plumes at the interface between fluid streams, suggesting strong
      complexation interactions between the dye and nanoparticles. These phenomena,
      driven by competition between the rates at which free tracer molecules are
      transported into the interfacial zone subsequently consumed by dye-nanoparticle
      complexation, have likely been incorrectly interpreted as anomalous diffusion
      enhancement. These interactions are important to consider when devising tracer
      based studies of nanoparticle suspensions and may lay a foundation for new
      adsorption-based analytical methods.

PMID- 20050688
TI  - Quantitative proteomic analysis reveals the perturbation of multiple cellular
      pathways in HL-60 cells induced by arsenite treatment.
AB  - Arsenic is ubiquitously present in the environment; it is a known human
      carcinogen and paradoxically it is also a successful drug for the clinical
      remission of acute promyelocytic leukemia (APL). The cellular responses induced
      by arsenite treatment have been investigated for years; however, the precise
      mechanisms underlying its cytotoxicity and therapeutic activity remain unclear.
      Here we report the use of mass spectrometry together with stable isotope labeling
      by amino acids in cell culture (SILAC) for the comparative study of protein
      expression in HL-60 cells that were untreated or treated with a clinically
      relevant concentration of arsenite. Our results revealed that, among the 1067
      proteins quantified in both forward and reverse SILAC measurements, 56 had
      significantly altered levels of expression induced by arsenite treatment. These
      included the up-regulation of core histones, neutrophil elastase, alpha
      mannosidase as well as the down-regulation of fatty acid synthase and protein
      phosphatase 1 alpha. We further demonstrated that the arsenite-induced growth
      inhibition of HL-60 cells could be rescued by treatment with palmitate, the final
      product of fatty acid synthase, supporting that arsenite exerts its cytotoxic
      effect, in part, via suppressing the expression of fatty acid synthase and
      inhibiting the endogenous production of fatty acid. The results from the present
      study offered important new knowledge for gaining insights into the molecular
      mechanisms of action of arsenite.

PMID- 20050690
TI  - Synthesis of crown ether-linked discotic triphenylenes.
AB  - Novel triphenylene dimers linked by a central crown ether core have been
      synthesized and characterized. The crown ether is most conveniently formed as a
      final step to permit purification and isolation of ion-free material, and
      extension of the protocol permits synthesis of triad structures linked though a
      27-crown-9 macrocycle. The latter compounds present a new discotic motif that
      supports mesophase formation.

PMID- 20050691
TI  - Stretchable, porous, and conductive energy textiles.
AB  - Recently there is strong interest in lightweight, flexible, and wearable
      electronics to meet the technological demands of modern society. Integrated
      energy storage devices of this type are a key area that is still significantly
      underdeveloped. Here, we describe wearable power devices using everyday textiles
      as the platform. With an extremely simple "dipping and drying" process using
      single-walled carbon nanotube (SWNT) ink, we produced highly conductive textiles
      with conductivity of 125 S cm(-1) and sheet resistance less than 1 Omega/sq. Such
      conductive textiles show outstanding flexibility and stretchability and
      demonstrate strong adhesion between the SWNTs and the textiles of interest.
      Supercapacitors made from these conductive textiles show high areal capacitance,
      up to 0.48F/cm(2), and high specific energy. We demonstrate the loading of
      pseudocapacitor materials into these conductive textiles that leads to a 24-fold
      increase of the areal capacitance of the device. These highly conductive textiles
      can provide new design opportunities for wearable electronics and energy storage
      applications.

PMID- 20050692
TI  - Steering epitaxial alignment of Au, Pd, and AuPd nanowire arrays by atom flux
      change.
AB  - We have synthesized epitaxial Au, Pd, and AuPd nanowire arrays in vertical or
      horizontal alignment on a c-cut sapphire substrate. We show that the vertical and
      horizontal nanowire arrays grow from half-octahedral seeds by the correlations of
      the geometry and orientation of seed crystals with those of as-grown nanowires.
      The alignment of nanowires can be steered by changing the atom flux. At low atom
      deposition flux vertical nanowires grow, while at high atom flux horizontal
      nanowires grow. Similar vertical/horizontal epitaxial growth is also demonstrated
      on SrTiO(3) substrates. This orientation-steering mechanism is visualized by
      molecular dynamics simulations.

PMID- 20050693
TI  - Designing 3D COFs with enhanced hydrogen storage capacity.
AB  - Hydrogen storage properties have been studied on newly designed three-dimensional
      covalent-organic framework (3D-COF). The design of these materials was based on
      the ctn network of the ultralow density COF-102. The structures were optimized by
      multiscale techniques and the optimized structures were checked for their storage
      capacities by grand canonical Monte Carlo simulations. Our simulations
      demonstrate that the gravimetric uptake of one of these new COFs can overpass the
      value of 25 wt % in 77 K and reach the Department of Energy's target of 6 wt % in
      room temperature, classifying them between the top hydrogen storage materials.

PMID- 20050694
TI  - Tuning of sorted double-walled carbon nanotubes by electrochemical charging.
AB  - Double-walled carbon nanotubes sorted by density gradient ultracentrifugation
      were examined by Raman spectroscopy and by in situ Raman spectroelectrochemistry.
      The sorted samples had a narrow distribution of diameters of both inner and outer
      tubes, which enabled a comparison of the behavior of inner metallic tubes and
      inner semiconducting nanotubes as a function of the applied electrochemical
      potential. The metallic inner tubes were efficiently doped even though they were
      protected from electrolyte ions by the outer wall, whereas the doping of
      semiconducting inner tubes was observed only at high magnitudes of the electrode
      potential. These results indicate that the doping response of inner tubes is
      predominantly controlled by inner tube electronic properties. On the other hand,
      the effect of electronic structure of the outer tube on the behavior of inner
      tube is weak. Furthermore, the efficiency of the charge transfer from outer to
      inner wall depends on the doping level. A low doping level corresponds to a high
      efficiency of the charge-transfer, while a high doping level shows low charge
      transfer efficiency.

PMID- 20050695
TI  - Enhancement and quenching regimes in metal-semiconductor hybrid optical
      nanosources.
AB  - We report on the emission of hybrid nanosources composed of gold nanoparticles
      coupled with quantum dots. The emission relies on energy transfer from the
      quantum dots to gold nanoparticles which could be de-excited through radiative
      plasmon relaxation. The dependence of the emission efficiency is studied
      systematically as a function of the size of gold nanoparticles and interdistance
      between gold nanoparticles and quantum dots. We demonstrate a size-dependent
      transition between quenching and enhancement and a nonradiative energy transfer
      from the quantum dots to the gold nanoparticles.

PMID- 20050696
TI  - Synthesis of enantioenriched allenes from 1,1-cyclopropanediesters.
AB  - Highly substituted allenes were obtained by the S(N)2' addition of organocuprate
      reagents on 2-propargyl-1,1-cyclopropanediesters. This new methodology permits
      the synthesis of highly enantioenriched allenes as the reaction proceeds with
      retention of the enantiomeric purity of the starting cyclopropane. The use of
      higher order cuprates was instrumental in obtaining the reported results.

PMID- 20050697
TI  - Porous coordination polymer with flexibility imparted by coordinatively
      changeable lithium ions on the pore surface.
AB  - Solvothermal reactions of equimolar zinc acetate, lithium acetate, and 1,3,5
      benzenetricarboxylic acid (H(3)btc) in different mixed solvents yielded
      isostructural three-dimensional frameworks [LiZn(btc)(cG)].lG [cG and lG denote
      coordinated and lattice guests, respectively; cG = (nmp)(0.5)(H(2)O)(0.5), lG =
      (EtOH)(0.5) (1a); cG = H(2)O, lG = EtOH (1b); nmp = N-methyl-2-pyrrolidone] with
      one-dimensional channels occupied by guest molecules and solvent-coordinated,
      extrusive Li(+) ions. Thermogravimetry analyses and powder X-ray diffraction
      measurements revealed that both 1a and 1b can lose all lattice and coordinated
      guests to form a desolvated phase [LiZn(btc)] (MCF-27, 1) and almost retains the
      original framework structure. Gas adsorption measurements on 1 confirmed its
      permanent porosity but suggested a structural transformation from 1a/1b to 1. It
      is noteworthy that only 1a can undergo a single-crystal to single-crystal (SCSC)
      transformation into 1 upon desolvation. The crystal structure of 1 revealed that
      the Li(+) ions were retracted into the channel walls via complementary
      coordination to the carboxylate oxygen atoms in the framework rather than being
      exposed on the pore surface. Single-crystal X-ray diffraction analyses were also
      performed for N(2)- and CO(2)-loaded samples of 1, revealing that the framework
      remained unchanged when the gases were adsorbed. Although the gas molecules could
      not be modeled, the residue electrons inside the channels demonstrated that the
      retracted Li(+) ions still behave as the primary interacting site for CO(2)
      molecules. Nevertheless, solvent molecules such as H(2)O can readily compete with
      the framework oxygen atom to retrieve the extrusive Li(+) ions, accompanying the
      reverse structural transformation, i.e., from 1 to 1a/1b.

PMID- 20050698
TI  - Role of prolyl cis/trans isomers in cyclophilin-assisted Pseudomonas syringae
      AvrRpt2 protease activation.
AB  - In a process contributing to the innate immunity of higher plants, Arabidopsis
      thaliana cyclophilin ROC1 induces the self-cleavage of Pseudomonas syringae
      putative cysteine protease AvrRpt2, triggering limited cleavage of A. thaliana
      RIN4, a negative regulator of plant immunity. We report an increase in AvRpt2
      activity in hydrolysis of decapeptide substrates at -GG- sites of more than 5
      orders of magnitude, in the presence of cyclophilin-like peptidyl prolyl
      cis/trans isomerases including ROC1 or hCyp18. Both full-length AvrRpt2 and its
      21 kDa self-cleavage product (AvrRpt2(72-255)) were found to be equally active
      under these conditions. In contrast to classical isomer-specific proteolysis,
      inertness toward cleavage of a cis/trans prolyl bond isomer at the substrate P4
      subsite is not the cause of cyclophilin-mediated activation of the proteolytic
      reaction. Monitoring single- and double-jump kinetics of proteolytic reactions in
      the presence of the PPIase inhibitor cyclosporin A revealed that the cis/trans
      ratio of potentially relevant prolyl bonds of AvrRpt2(72-255) remained the same
      in the functionally inactive state of AvrRpt2(72-255) and the productive
      AvrRpt2(72-255)-cyclophilin-substrate complex.

PMID- 20050699
TI  - Structural and kinetic characterization of the LPS biosynthetic enzyme D
      alpha,beta-D-heptose-1,7-bisphosphate phosphatase (GmhB) from Escherichia coli.
AB  - Lipopolysaccharide is a major component of the outer membrane of gram-negative
      bacteria and provides a permeability barrier to many commonly used antibiotics.
      ADP-heptose residues are an integral part of the LPS inner core, and mutants
      deficient in heptose biosynthesis demonstrate increased membrane permeability.
      The heptose biosynthesis pathway involves phosphorylation and dephosphorylation
      steps not found in other pathways for the synthesis of nucleotide sugar
      precursors. Consequently, the heptose biosynthetic pathway has been marked as a
      novel target for antibiotic adjuvants, which are compounds that facilitate and
      potentiate antibiotic activity. D-alpha,beta-D-heptose-1,7-bisphosphate
      phosphatase (GmhB) catalyzes the third essential step of LPS heptose
      biosynthesis. This study describes the first crystal structure of GmhB and
      enzymatic analysis of the protein. Structure-guided mutations followed by steady
      state kinetic analysis, together with established precedent for HAD phosphatases,
      suggest that GmhB functions through a phosphoaspartate intermediate. This study
      provides insight into the structure-function relationship of GmhB, a new target
      for combatting gram-negative bacterial infection.

PMID- 20050700
TI  - Fast synthesis of N-acylhydrazones employing a microwave assisted neat protocol.
AB  - A variety of N-acylhydrazones were synthesized under microwave irradiation within
      2.5-10 min, starting from benzo, salicyloyl, and isonicotinic hydrazides. The
      protocol developed employs microwave irradiation in the absence of solvents and
      catalysts, leading to high yields. The results are reproducible in a 500 mg to 5
      g scale.

PMID- 20050701
TI  - "Citation classics" and classic citations in JAFC.

PMID- 20050702
TI  - Use of ATR-FTIR microspectroscopy to monitor autolysis of Saccharomyces
      cerevisiae cells in a base wine.
AB  - In this study, we evaluated the potentialities of ATR-FTIR microspectroscopy
      coupled to PCA in monitoring the major biochemical changes that occur during the
      autolysis of yeasts used for sparkling wine production. For this purpose, mid
      infrared measurements were made on cells of the model strain Saccharomyces
      cerevisiae EC1118 in the course of autolysis induced at 30 degrees C for five
      days in a model and in a base wine. By relating principal component loadings to
      the corresponding absorption bands, it was shown that they well describe
      compositional modifications induced by autolytic process on yeast cells, such as
      partial hydrolysis of proteins, increase of peptides, free nucleotides, lipids,
      mannans, and beta-1,3 glucans. The corresponding score-score plots allowed us to
      monitor the different kinetics and to distinguish among faster, intermediate, and
      slower processes. ATR-FTIR microspectroscopy coupled with PCA is proposed as a
      sensitive method that can provide useful information to select efficient yeast
      strains, capable of accelerated autolysis, to be used in the second fermentation
      and aging of sparkling wines.

PMID- 20050703
TI  - Evaluation of different teas against starch digestibility by mammalian
      glycosidases.
AB  - Current work investigated the ability of different tea (green, oolong and black
      teas) in inhibiting human salivary alpha-amylase (HSA) and mammalian alpha
      glucosidase (AGH). The inhibitory profiles were correlated to their major
      polyphenol content (theaflavins and catechins). The fully fermented black tea was
      demonstrated to be most potent in inhibiting HSA and AGH (IC50 of 0.42 to 0.67
      and 0.56 to 0.58 mg of tea leaves/mL respectively). Its capability in retarding
      the digestion of a real food system (rice noodle) was further elucidated with an
      in vitro digestion study. Results indicated that black tea was able to retard
      starch digestion moderately, thereby allowing a gradual reduction of sugar
      liberation. Polyphenolic profile analysis suggested that the oxidized catechins,
      theaflavins, may be responsible for its activity. We have found that refractive
      index (RI) measurement is a rapid, direct, and highly convenient method for
      quantifying the degree of enzymatic starch digestion and kinetics. The RI method
      has good linearity range, limit of detection (0.1596 mg/mL, maltose equivalent)
      and limit of quantitation (0.6312 mg/mL) and was successfully applied in our
      study.

PMID- 20050704
TI  - Effect of gel firmness at cutting time, pH, and temperature on rennet coagulation
      and syneresis: an in situ 1H NMR relaxation study.
AB  - The objective of this study was to monitor rennet-induced milk gel formation and
      mechanically induced gel syneresis in situ by low-field NMR. pH, temperature, and
      gel firmness at cutting time were varied in a factorial design. The new curve
      fitting method Doubleslicing revealed that during coagulation two proton
      populations with distinct transverse relaxation times (T2,1=181, T2,2=465 ms)
      were present in fractions (f1=98.9%, f2=1.1%). Mechanical cutting of the gel in
      the NMR tube induced macrosyneresis, which led to the appearance of an additional
      proton population (T2,3=1500-2200 ms) identified as whey. On the basis of NMR
      quantification of whey water the syneresis rate was calculated and found to be
      significantly dependent on pH and temperature.

PMID- 20050705
TI  - Antihypertensive effect of a gamma-aminobutyric acid rich tomato cultivar 'DG03
      9' in spontaneously hypertensive rats.
AB  - This study aimed to investigate the effects of a gamma-aminobutyric acid (GABA)
      rich tomato (Solanum lycopersicum L.) cultivar 'DG03-9' in comparison with
      'Momotaro', a commonly consumed tomato cultivar in Japan, on systolic blood
      pressure (SBP) in spontaneously hypertensive rats (SHR). In a single
      administration study, treatment with the GABA-rich cultivar elicited a
      significant decrease in SBP compared to the control group. In a chronic
      administration study, SHR were fed diets containing one of the tomato cultivars
      for 4 weeks. Both cultivars significantly reduced the increase in SBP compared to
      the control. The antihypertensive effect of the GABA-rich cultivar was higher
      than that of the commonly consumed cultivar in both the single- and chronic
      administration studies. Treatment with a comparable amount of GABA elicited a
      similar response to treatment with the GABA-rich cultivar. These results suggest
      that the GABA-rich cultivar 'DG03-9' is a potent antihypertensive food and may be
      useful for treating hypertension effectively.

PMID- 20050706
TI  - Flavonol glycosides of sea buckthorn (Hippophae rhamnoides ssp. sinensis) and
      lingonberry (Vaccinium vitis-idaea) are bioavailable in humans and
      monoglucuronidated for excretion.
AB  - Glucuronidation and excretion of sea buckthorn and lingonberry flavonols were
      investigated in a postprandial trial by analyzing the intact forms of flavonol
      glycosides as well as glucuronides in plasma, urine, and feces. Four study
      subjects consumed sea buckthorn (study day 1) and lingonberry (study day 2)
      breakfasts, and blood, urine, and fecal samples were collected for 8, 24, and 48
      h, respectively. Both glycosides and glucuronides of the flavonol quercetin as
      well as kaempferol glucuronides were detected in urine and plasma samples after
      the consumption of lingonberries; 14% of flavonols in urine were glycosides, and
      86% were glucuronidated forms (wt %). After the consumption of sea buckthorn, 5%
      of flavonols excreted in urine were detected intact, and 95% as the glucuronides
      (wt %). Solely glucuronides of flavonols isorhamnetin and quercetin were found in
      plasma after the consumption of sea buckthorn berries. Only glycosides were
      detected in the feces after each berry trial. Flavonol glycosides and
      glucuronides remained in blood and urine quite long, and the peak concentrations
      appeared slightly later than previously described. The berries seemed to serve as
      a good flavonol supply, providing steady flavonol input for the body for a
      relatively long time.

PMID- 20050708
TI  - A novel approach using hierarchical clustering to select industrial chemicals for
      environmental impact assessment.
AB  - We propose a four-step strategy, based on principal component analysis and
      hierarchical clustering, for selecting structurally dissimilar organic substances
      from a list of commercial, high volume production chemicals. The selection
      strategy also presents alternative structures with similar characteristics, so
      that practical aspects of future testing can be easily addressed. The selected
      compounds listed in this Article are intended for further study regarding their
      environmental impact and as potential pollutants.

PMID- 20050707
TI  - Protein (19)F NMR in Escherichia coli.
AB  - Although overexpression and (15)N enrichment facilitate the observation of
      resonances from disordered proteins in Escherichia coli, (15)N enrichment alone
      is insufficient for detecting most globular proteins. Here, we explain this
      dichotomy and overcome the problem while extending the capability of in-cell NMR
      by using (19)F-labeled proteins. Resonances from small (approximately 10 kDa)
      globular proteins containing the amino acid analogue 3-fluoro-tyrosine can be
      observed in cells, but for larger proteins the (19)F resonances are broadened
      beyond detection. Incorporating the amino acid analogue trifluoromethyl-L
      phenylalanine allows larger proteins (up to 100 kDa) to be observed in cells. We
      also show that site-specific structural and dynamic information about both
      globular and disordered proteins can be obtained inside cells by using (19)F NMR.

PMID- 20050709
TI  - Potentiometric titrations of five synthetic tetraacids as models for indigenous
      C80 tetraacids.
AB  - The acid/base properties, critical micelle concentrations (cmcs), and pH
      dependent solubility of five synthetic tetraacids have been studied at several
      ionic strengths (20-600 mM NaCl) and in the pH range of 1.5-11 using high
      precision potentiometric titrations, tensiometer measurements, and UV
      spectroscopy, respectively. The molecular weight of the tetraacids ranged between
      478 and 983 g/mol. The potentiometric titration data was evaluated in terms of
      thermodynamic equilibrium models, developed in the light of relevant solubility
      data, Langmuir monolayer compressions and cmc of the different tetraacids. The
      results indicate that for two of the tetraacids, called BP5 and BP7, two chemical
      forms fully dominate the speciation of the monomers; the insoluble fully
      protonated form, and the soluble fully deprotonated form. The partly protonated
      species, only play a very minor role in the speciation of these tetraacids. For
      the other tetraacids the results are more complicated; for the smallest
      tetraacid, called BP1, all species seem to play important roles, and for the most
      hydrophobic, BP10, the formation of micelles and aggregates severely complicates
      the evaluation of the speciation. For the tetraacid BP3 one of the partly
      deprotonated forms seems to be important, thus confirming the structure to
      properties relationship. In spite of the complicated micelle formation chemistry,
      and although not actually measured, the acid/base properties for the monomers of
      BP10 were interpreted by means of surface charge densities of the micellar
      aggregates. The modeling indicates an increase of the aggregation number of the
      micelle upon acidification, a result of formation of mixed micelles incorporating
      the fully protonated and deprotonated species. An intrinsic pK(a) of 5.4 for BP5
      was used to model the monomer pK(a) of BP10, and corresponded well with a
      monolayer acidity constant pK(s)(a) of 5.5 obtained from surface collapse
      pressures of Langmuir monolayers as a function of pH.

PMID- 20050710
TI  - Study of pentafluoroethane and its thermal decomposition using UV photoelectron
      spectroscopy and ab initio molecular orbital calculations.
AB  - The UV photoelectron spectrum of CF(3)CHF(2) has been recorded and assigned using
      EOM-CCSD calculations. For the first band, the adiabatic ionization energy (AIE)
      and vertical ionization energy (VIE) have been measured as (12.71 +/- 0.05) and
      (13.76 +/- 0.02) eV, respectively. The measured AIE is higher than the
      recommended value from state-of-the-art ab initio calculations of (12.26 +/-
      0.02) eV because of a large geometry change on ionization, mainly arising from a
      significant increase in the C-C bond length, which results in poor Franck-Condon
      factors in the adiabatic region. The experimental VIE also shows poor agreement
      with the computed value of 14.05 +/- 0.06 eV because, in the higher energy region
      of the first photoelectron band, dissociation of CF(3)CHF(2)(+) to CHF(2)(+) +
      CF(3) occurs. This has a calculated thermodynamic onset of (12.89 +/- 0.20) eV.
      Recommendations are made for the heats of formation, DeltaH(f,298)(slashed
      circle), of CF(3)CHF(2) and CF(3)CHF(2)(+), based on the results of the ab initio
      calculations. Pyrolysis of flowing CF(3)CHF(2) diluted in argon shows evidence of
      production of C(2)F(4) and HF at lower temperatures and CF(2) and CF(3)H at
      higher temperatures. The relative temperature dependence of the observed
      photoelectron bands associated with these molecules is interpreted in terms of
      two decomposition reactions of CF(3)CHF(2) as well as the reaction C(2)F(4) -->
      2CF(2).

PMID- 20050711
TI  - Photodissociation dynamics of propargyl alcohol at 212 nm: the OH production
      channel.
AB  - Photodissociation dynamics of propargyl alcohol (HC identical withC-CH(2)OH) at
      212 nm in the gas phase was investigated by measuring rotationally resolved laser
      induced fluorescence spectra of OH ((2)Pi) radicals exclusively produced in the
      ground electronic state. From the spectra, internal energies of OH and
      translational energy releases to products were determined. The electronic
      transition at 212 nm responsible for the OH dissociation was assigned as the
      pi(C[triple bond]C) --> pi*(C[triple bond]C) transition by time-dependent density
      functional theory calculations. In addition, an energy barrier at the exit
      channel along the reaction coordinate on the excited electronic potential energy
      surface was identified by ab initio calculations. The observed energy
      partitioning among the fragments was successfully modeled by the so-called
      "barrier-impulsive model".

PMID- 20050712
TI  - Measurements of the equilibrium size of supersaturated aqueous sodium chloride
      droplets at low relative humidity using aerosol optical tweezers and an
      electrodynamic balance.
AB  - An approach for examining the hygroscopicity of single aerosol particles over a
      broad range in relative humidity (RH) using aerosol optical tweezers is presented
      and compared with measurements made using an electrodynamic balance. In
      particular, benchmark measurements on aqueous sodium chloride aerosol are
      presented over the RH range 45-75% (293 K), a RH range that had not previously
      been explored with aerosol optical tweezers. Measurements of the variation in
      equilibrium wet droplet size with RH are made using cavity-enhanced Raman
      scattering, with an accuracy of 1 nm in the determination of the wet particle
      radius. The full range of optical tweezers experimental measurements (including
      previous dual trapping comparative studies approaching a saturation relative
      humidity of 100%) are compared with determinations using other experimental
      techniques and with a range of model treatments. An assessment of the models and
      all experimental data for estimating the equilibrium size of a sodium chloride
      droplet suggests that the size can be predicted with an accuracy of better than
      0.1% over the RH range 48-100%. Discrepancies between different measurements lead
      to an increase in uncertainty above 1% below an RH of 48% as efflorescence is
      approached. The optical tweezers' measurements of equilibrium size consistently
      agree with model predictions to within an error of 1% (<50 nm for the size range
      explored here) and mostly with an error of less than +/-0.1%. These data
      demonstrate the highly accurate nature of measurements of thermodynamic
      equilibrium size by aerosol optical tweezers and suggest that this approach may
      be used to investigate the competition between thermodynamic and kinetic factors
      in governing aerosol particle size over the full RH range.

PMID- 20050713
TI  - One-electron oxidation of individual DNA bases and DNA base stacks.
AB  - In calculations performed with DFT there is a tendency of the purine cation to be
      delocalized over several bases in the stack. Attempts have been made to see if
      methods other than DFT can be used to calculate localized cations in stacks of
      purines, and to relate the calculated hyperfine couplings with known experimental
      results. To calculate reliable hyperfine couplings it is necessary to have an
      adequate description of spin polarization which means that electron correlation
      must be treated properly. UMP2 theory has been shown to be unreliable in
      estimating spin densities due to overestimates of the doubles correction.
      Therefore attempts have been made to use quadratic configuration interaction
      (UQCISD) methods to treat electron correlation. Calculations on the individual
      DNA bases are presented to show that with UQCISD methods it is possible to
      calculate hyperfine couplings in good agreement with the experimental results.
      However these UQCISD calculations are far more time-consuming than DFT
      calculations. Calculations are then extended to two stacked guanine bases.
      Preliminary calculations with UMP2 or UQCISD theory on two stacked guanines lead
      to a cation localized on a single guanine base.

PMID- 20050714
TI  - Identification of amino acids responsible for processivity in a Family 1
      carbohydrate-binding module from a fungal cellulase.
AB  - We probe the molecular-level behavior of the Family 1 carbohydrate-binding module
      (CBM) from a commonly studied fungal cellulase, the Family 7 cellobiohydrolase
      (Cel7A) from Trichoderma reesei, on the hydrophobic face of crystalline
      cellulose. With a fully atomistic model, we predict that the CBM alone exhibits
      regions of thermodynamic stability along a cellulose chain corresponding to a
      cellobiose unit, which is the catalytic product of the entire Cel7A enzyme. In
      addition, we determine which residues and the types of interactions that are
      responsible for the observed processivity length scale of the CBM: Y5, Q7, N29,
      and Y32. These results imply that the CBM can anchor the Cel7A enzyme at discrete
      points along a cellulose chain and thus aid in both recognizing cellulose chain
      ends for initial attachment to cellulose as well as aid in enzymatic catalysis by
      diffusing between stable wells on a length scale commensurate with the catalytic,
      processive cycle of Cel7A during cellulose hydrolysis. Comparison of other Family
      1 CBMs show high functional homology to the four amino acids responsible for the
      processivity length scale on the surface of crystalline cellulose, which suggests
      that Family 1 CBMs may generally employ this type of approach for translation on
      the cellulose surface. Overall, this work provides further insight into the
      molecular-level mechanisms by which a CBM recognizes and interacts with
      cellulose.

PMID- 20050715
TI  - Analysis of the magnetic coupling in M3(dpa)4Cl2 systems (M = Ni, Pd, Cu, Ag) by
      ab initio calculations.
AB  - The magnetic exchange parameter (J) of a series of neutral and oxidized
      trinuclear extended metal atom chain complexes [M(3)(dpa)(4)Cl(2)](0/1+), where
      dpa is the anion of di(2-pyridyl)amine, has been extracted employing the complete
      active space second-order perturbation theory (CASPT2). The computed magnetic
      coupling constant for Ni(3)(dpa)(4)Cl(2) (-98 cm(-1)) and the mono-oxidized Cu(3)
      complex (-35 cm(-1)) are in excellent agreement with the experimental estimates.
      This consistence is though not achieved for Cu(3)(dpa)(4)Cl(2), with three S =
      1/2 magnetic centers, for which we surprisingly obtain 1/3 of the experimental
      value only. This worrying result and the possible sources for such large
      discrepancy are analyzed. The magnetic coupling has been also analyzed for the
      hypothetical complexes with Pd(3) and Ag(3) metal chains. Much larger couplings
      are obtained, which is ascribed to the larger spatial extent of the magnetic
      orbitals. Furthermore, we analyze the relative importance of the magnetic
      coupling paths through the sigma-system (through metal coupling) and the delta
      system (through ligand coupling).

PMID- 20050716
TI  - Fever of unknown origin in an infant with an unexpected blood film report: a case
      report.
AB  - INTRODUCTION: Fever of unknown origin (FUO) can be defined as a rectal
      temperature higher than 38.3 degrees C on several occasions over more than 3
      weeks, the diagnosis of which remains uncertain after initial investigations.
      Identification of the causes and management of FUO in children is an important
      role of rural primary care physicians, and is guided by thorough history-taking
      and repeated physical examinations combined with standard laboratory tests and
      simple imaging procedures. This can be difficult in rural practice due to poor
      availability and reliability of laboratory and imaging procedures, and the cost
      and misuse of antibiotics. Dependence on clinical and laboratory examinations may
      fail in diseases presenting in non-endemic areas. Trypanosomiasis is a known
      cause of fever; however, it is an unusual cause of FUO considering the place of
      residence of this patient. CASE REPORT: This report describes a case of
      trypanosomiasis presenting as FUO. The patient was a one-year-old Nigerian female
      who had been managed for malaria and bronchopneumonia for 2 weeks in a private
      clinic and was finally referred for further management to Eku Baptist Hospital, a
      rural mission hospital in the Niger Delta of Nigeria. Results of her laboratory
      tests showed nothing of significance apart from anaemia and trypanosomes
      discovered unexpectedly in the blood film. This was confirmed after a cervical
      lymph node biopsy and microscopic examination of the glandular fluid. Treatment
      with eflornithine was effective. CONCLUSION: The diagnosis of trypanosomiasis in
      this patient highlights that when a patient is not obviously exposed to the
      causative factors of a disease, possible occurrences may present a diagnostic
      problem.

PMID- 20050717
TI  - Amisulpride versus olanzapine in the treatment of schizophrenia in Indian
      patients: randomized controlled trial.
AB  - OBJECTIVE: Atypical antipsychotics are increasingly drugs of first choice in
      schizophrenia. Amisulpride, a new atypical antipsychotic, is reported to be
      effective for both positive and negative symptoms of schizophrenia in Western
      countries but Indian experience is limited. The aim of the present study was
      therefore to conduct a trial of amisulpride versus olanzapine in Indian
      schizophrenia patients. METHODS: Eighty adult patients of either sex were
      randomized to receive standard doses of the two drugs orally, in a single blind
      manner, for 12 weeks, with follow up at 4 and 8 weeks. Effectiveness was assessed
      by changes in scores on the Brief Psychiatric Rating Scale (BPRS), Scale for
      Assessment of Positive Symptoms (SAPS), Scale for Assessment of Negative Symptoms
      (SANS), and physician-administered Clinical Global Impression (CGI) scale.
      Tolerability was assessed by treatment-emergent adverse drug reactions (ADRs).
      RESULTS: Evaluable were 39 patients on amisulpride and 38 on olanzapine. The
      groups were comparable at baseline with respect to demographics, illness duration
      and rating scores. Final BPRS score was lower for olanzapine (33.2 +/- 9.44) than
      for amisulpride (37.7 +/- 9.67). SAPS and SANS scores and CGI rating improved
      individually in both arms but remained comparable between groups throughout the
      study period, but olanzapine reduced SAPS score to a greater extent. ADRs were
      encountered in 67.5% and 47.5% of patients (p = 0.113) on amisulpride and
      olanzapine, respectively. Tremor and insomnia were more frequent with
      amisulpride, while olanzapine caused more weight gain and sedation. No serious
      ADRs occurred. CONCLUSIONS: Amisulpride, although comparable to olanzapine on
      some measures, did not match the improvement seen with the latter drug in BPRS
      and SAPS scores. Despite differences in ADR profiles, overall tolerability was
      satisfactory for both drugs. In Indian patients, amisulpride should therefore be
      an alternative to olanzapine to a limited extent, such as when weight gain and
      sedation are undesirable.

PMID- 20050718
TI  - Use of the Repeatable Battery for the Assessment of Neuropsychological Status
      (RBANS) to investigate group and gender differences in schizophrenia and bipolar
      disorder.
AB  - OBJECTIVE: Gender differences exist in schizophrenia and bipolar disorder (BD),
      therefore the aim of the present study was to clarify the role of gender in
      cognitive deficits in these disorders. METHODS: Cognitive performance was
      examined in schizophrenia (24M : 14F) and BD (16M : 24F) patients compared with
      age-, IQ- and gender-matched control participants (21M : 22F). The Repeatable
      Battery for the Assessment of Neuropsychological Status (RBANS) was used to
      assess five cognitive domains: immediate memory/learning, visuospatial ability,
      language, attention, and delayed memory, which are summed to provide a Total
      score. RESULTS: In comparison to controls, schizophrenia patients showed deficits
      on all domains, while BD patients had impaired immediate memory/learning,
      language and Total score. Schizophrenia patients showed deficits compared to BD
      in the Total score, immediate and delayed memory and visuospatial ability. The
      Total and domain scores were not different in men and women across or within
      groups. There were gender effects on four of the 12 individual cognitive tasks,
      in which female patients outperformed male patients. Further, there were gender
      differences across groups for three of the individual tasks: female schizophrenia
      patients showed poorer story memory and story recall compared to male
      schizophrenia patients; female BD patients had enhanced figure copy performance
      compared to male BD patients. CONCLUSIONS: The RBANS highlighted the cognitive
      deficits in schizophrenia and BD patients compared to controls and also each
      other. There were no overall gender differences in cognition.

PMID- 20050719
TI  - A brief measure of vocational activity and community participation: development
      and reliability of the Activity and Participation Questionnaire.
AB  - OBJECTIVES: Social and economic marginalization are significant problems for many
      people living with mental illness. Clinicians and policy-makers have increased
      their focus on these aspects of recovery. Current outcome measures, however, do
      not support this focus, and detailed functional measures are not suitable for
      routine clinical use. This report describes the development and test-retest
      reliability of the Activity and Participation Questionnaire (APQ6); a self-report
      measure of vocational activity and social participation for routine use in
      community mental health services. METHOD: The APQ6 was developed from concepts of
      the Australian Bureau of Statistics Labour Force Surveys and Census. Field
      testing and consumer consultation were undertaken in New South Wales (NSW) mental
      health rehabilitation services. Test-retest reliability trials were conducted
      simultaneously by research teams in NSW and Queensland. RESULTS: Pairs of short
      cycle test-retest reliability interviews were obtained from 129 mental health
      service consumers. Consumer feedback and test-retest reliability results at
      question and item levels indicate good construct validity. The measure has
      utility as both a telephone and a personal interview in community mental health
      settings. CONCLUSIONS: The reported psychometric properties support the proposed
      use of the APQ6 as a recovery-orientated measure focusing on vocational activity
      and community participation. The APQ6 is being introduced for routine use by NSW
      mental health services.

PMID- 20050720
TI  - Increased risk of acute myocardial infarction after acute episode of
      schizophrenia: 6 year follow-up study.
AB  - OBJECTIVE: The aim of the present study was to estimate the risk of acute
      myocardial infarction (AMI) among patients who received a first hospital
      diagnosis of schizophrenia during a 6 year follow-up period. METHOD: Data from
      the Taiwan National Health Insurance Research Database were used. The study
      cohort consisted of 7353 patients who were hospitalized with a principal
      diagnosis of schizophrenia in 2000. The comparison cohort were 22 059 enrollees
      randomly selected matched with the study group in terms of gender and age. Each
      patient was tracked from their index hospitalization in 2000 until the end of
      2006 to identify whether or not an AMI had occurred during the follow-up period.
      Cox proportional hazard regressions were performed to compute the adjusted 6 year
      survival rate, following adjustment for possible confounding variables. RESULTS:
      A total of 130 patients suffered AMI during the 6 year follow-up period,
      including 30 from the study cohort (0.41% of the schizophrenia patients), and 100
      (0.45%) from the comparison cohort. But after censoring those patients who died
      from non-AMI causes and adjusting for potential confounding factors, the risk of
      AMI occurrence during the 6 year follow-up period was 1.83-fold greater for
      schizophrenia patients (95% confidence interval 5 1.62-2.05) than for patients in
      the comparison cohort. CONCLUSION: Schizophrenia patients had a higher risk of
      AMI compared to patients in the comparison cohort. The present study draws
      attention to the need for clinicians to more actively monitor and treat
      schizophrenia patients with well-recognized risk factors associated with AMI.

PMID- 20050721
TI  - Sex differences in neuropsychological functioning among schizophrenia patients.
AB  - OBJECTIVES: Evidence from the literature addressing sex differences in cognition
      in schizophrenia remains equivocal, with some researchers suggesting that male
      schizophrenia patients are more impaired than female subjects, while others
      report no significant sex differences in cognitive functioning. The aim of the
      present study was to investigate whether the differential pattern of cognitive
      performance observed in healthy men and women is preserved in male and female
      schizophrenia patients. METHOD: Ninety-six schizophrenia patients (56 men) were
      compared with 62 age- and gender-ratio matched healthy controls (31 men), on a
      battery of neuropsychological tests that assessed basic cognitive abilities:
      attention, working memory, abstraction, inhibition, fluency, verbal learning and
      memory, visual memory, visuospatial skills, and psychomotor speed. RESULTS: As a
      group, schizophrenia patients were significantly impaired in each of the
      cognitive domains assessed, with the exception of psychomotor speed. The effect
      of sex was significant for verbal learning and memory, wherein women outperformed
      men. No significant group x sex interactions were found in any cognitive domains,
      indicating that the female advantage typically observed in verbal learning and
      memory remained the same in the schizophrenia patients. CONCLUSION: The degree of
      cognitive impairment is the same for male and female schizophrenia patients.
      Those sex differences found among the patients were typical of the healthy
      population as well. Therefore, differential decrements in basic cognitive domains
      do not appear to account for the favourable course of schizophrenia in women
      relative to men.

PMID- 20050722
TI  - Consistency of diagnostic thresholds in DSM-V.
AB  - OBJECTIVE: DSM-IV diagnostic criteria define thresholds on a continuum of
      symptoms above which the diagnosis is said to be established. Data from the 1997
      Australian Survey of Mental Health and Wellbeing were used for six internalizing
      disorders, and the levels of distress and disability associated with each
      diagnosis were investigated. METHOD: Mean distress (measured by the K-10) and
      disability (measured by the SF12-MCS) scores were identified for people in the
      Survey who reported no physical or mental disorders. The distribution of distress
      and disability showed by people who met criteria for major depressive disorder,
      dysthymia, generalized anxiety disorder, social phobia, post-traumatic stress
      disorder and obsessive-compulsive disorder was plotted against the mean for well
      people, expecting that > or = 90% of people with these mental disorders would
      score as more distressed or disabled than this mean. RESULTS: More than 90% of
      people with dysthymia, major depressive disorder, generalized anxiety disorder or
      with post-traumatic stress disorder scored as more distressed or disabled than
      the mean for well people. A majority were severely distressed or disabled (> 2SD
      above the mean). This remained the case when the clinical significance criteria
      were removed. In social phobia and in obsessive-compulsive disorders between 9%
      and 26% scored below the means for well people, that is, as neither distressed
      nor disabled, a figure that rose to 16-40% when the clinical significance
      criteria were removed. In neither case did a majority of cases score in the
      severe range. CONCLUSIONS: The diagnostic thresholds for social phobia and for
      obsessive-compulsive disorder are less stringent than that for the other
      disorders and require revision in DSM-V.

PMID- 20050723
TI  - Characteristics of Chinese service users in an old age psychiatry service in New
      Zealand.
AB  - OBJECTIVE: There is a paucity of research on the mental health issues of older
      Chinese people in New Zealand. This study aimed to describe the profiles of
      Chinese service users in a community-based old age psychiatry service. METHOD:
      There were 22 older Chinese service users at the time of this cross-sectional
      analysis. Information on their demographics, referral pattern, diagnosis and
      treatment was obtained from their medical records and compared with a sample of
      22 non-Chinese service users. RESULTS: The referral rates for Chinese and non
      Chinese were 0.8% and 1.2% respectively. There did not appear to be any
      differences in the gender ratio, mean age, referral sources, diagnosis and
      medication use in the Chinese and non-Chinese groups. The largest observed
      differences were the higher rates of physical aggression at referral, use of
      Mental Health Act and inpatient treatment in the Chinese group. These
      observations suggest there might have been a delay in seeking care until
      psychiatric symptoms became unmanageable. CONCLUSIONS: There is a need for
      further research to improve primary care, mental health service access and
      responsiveness for older Chinese and other Asian minority groups.

PMID- 20050724
TI  - Physicochemical study on microencapsulation of hydroxypropyl-beta-cyclodextrin in
      dermal preparations.
AB  - OBJECTIVE: To investigate the effect of hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) concentration on the physicochemical properties of the sunscreen agents,
      namely oxybenzone (Oxy), octocrylene (Oct), and ethylhexyl-methoxy-cinnamate
      (Cin), in aqueous solution and cream formulations. METHODS: The inclusion
      complexes of sunscreen agents with hydroxypropyl-beta-cyclodextrin (HP-beta-CD)
      in aqueous solution and solid phase were studied by UV-vis spectrophotmetery,
      differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and
      13C-NMR techniques. The photodegradation reaction of the sunscreen agents'
      molecules in lotion was explored using UV-vis spectrophotometry and high
      performance liquid chromatography (HPLC). RESULTS: The formation of the inclusion
      complexes was confirmed experimentally using DSC, SEM, and 13C-NMR. The results
      of spectrophotometric and HPLC studies have shown that the inclusion complexation
      with HP-beta-CD has the potential to enhance the photostability of the selected
      sunscreen agents in lotion. HPLC results indicated that HP-beta-CD has
      approximately increases the photostability of Oct by six- to eightfold. Moreover,
      the presence of HP-beta-CD in lotion controlled the isomerization process of Cin
      to a certain degree, which was found to be a function of the amount of HP-beta-CD
      added. CONCLUSIONS: It has been demonstrated that the photostability of the
      tested sunscreen agents has been enhanced upon forming inclusion complexes with
      HP-beta-CD in lotion. The results of this study demonstrate that HP-beta-CD can
      be utilized as photostabilizer additive for enhancing the photostability of the
      sunscreen agents' molecules.

PMID- 20050725
TI  - The composition of oil phase modulates venous irritation of lipid emulsion-loaded
      diallyl trisulfide.
AB  - INTRODUCTION: In this study, a nanoemulsion system (LE) was investigated for
      intravenous delivery of diallyl trisulfide (DT), which was a lipophilic and
      venous irritant drug for systemic therapy of bacterial and fungal infection.
      METHODS: Egg phospholipid was chosen as the only emulsifier, soybean oil, medium
      chain triglyceride (MCT), and olive oil were used as the oil phases, forming
      stable DT LEs (o/w) with small particle sizes. The venous irritation of DT LEs
      was evaluated by in vitro human umbilical cord endothelial cells (HUV-EC CRL
      1730) tolerance model with the intracellular ATP and GTP concentrations as the
      indices. RESULTS: The intracellular ATP and GTP reduction changed with the
      incorporation of a variety of oils, which were strongly related with the free DT
      concentration of DT LEs. DISCUSSION: It was deduced that the free DT
      concentrations of LEs made of various oils depended on the particle sizes of the
      DT LEs. In conclusion, the oil phases modulated the free DT concentrations by
      forming DT LEs with different particle sizes, and optimization of the oil phase
      was an effective method to alleviate the venous irritation of DT LEs.

PMID- 20050726
TI  - Combining strategies to optimize a gel formulation containing miconazole: the
      influence of modified cyclodextrin on textural properties and drug release.
AB  - BACKGROUND: Miconazol, an antimycotic drug, is commonly formulated into semisolid
      formulations designed to be applied in the oral cavity to treat oral candidiasis.
      However, given its limited aqueous solubility, permeation through the biological
      membranes is low and therefore its activity is also limited. Cyclodextrins (CDs)
      have been widely used to increase the solubility and stability of poorly water
      soluble drugs. AIM: The aim of this study is to formulate a gel containing an
      inclusion complex between a modified CD, methyl-beta-cyclodextrin (MbetaCD), and
      miconazole (MCZ). The influence of the CD on the textural properties of the
      prepared gel and the drug release from formulation were evaluated. METHODS: The
      gels were prepared using two polymers, Carbopol 71G and Pluronic F127, which were
      selected taking into account their bioadhesiveness and thermal-sensitive gelling
      properties, respectively. Texture profile analyses were performed at two
      different temperatures to ascertain the influence of the temperature on the gel
      texture properties. The in vitro MCZ release profiles from the prepared gel and
      the commercial gel formulations were evaluated and compared using modified Franz
      diffusion cells. RESULTS: The addition of MbetaCD to the gel resulted in a
      decrease of the gel adhesiveness and firmness, and the MCZ release profile
      through f1 and f2 proved to be similar to the commercial product. CONCLUSIONS: A
      gel comprising miconazol in the form of an inclusion complex with MbetaCD showed
      suitable textural properties to be applied to the buccal mucosa. The MbetaCD
      enhanced the solubility of the MCZ in the gel formulation resulting in adequate
      in vitro drug release profiles.

PMID- 20050727
TI  - Techniques to assess film coatings and evaluate film-coated products.
AB  - BACKGROUND: Polymeric film coatings have been applied to pharmaceutical solids
      for decorative, protective, or functional purposes. The application process is
      quite complex, with variables related to the coating formulation, substrate
      properties, processing parameters, and interactions thereof, all of which can
      affect product performance. OBJECTIVE: This article describes a number of
      experimental techniques used to determine the physical, mechanical, adhesive,
      thermal, and permeability properties of free and applied films. These analytical
      tools can be used to optimize product performance, advance our knowledge of the
      film formation process, and investigate interactions between the coating and the
      solid surface. CONCLUSION: Through a better understanding of film-coating
      processes, the cause of problems that arise during manufacturing, defects
      observed in the coating, and changes in performance upon subsequent storage may
      be more quickly and accurately resolved.

PMID- 20050728
TI  - Determination of factors affecting kinetics of solid-state transformation of
      fluconazole polymorph II to polymorph I using diffuse reflectance Fourier
      transform spectroscopy.
AB  - BACKGROUND: It was of interest to investigate the factors affecting kinetics of
      transformation of fluconazole polymorph II (the metastable form) to fluconazole
      polymorph I (the stable form) using diffuse reflectance infrared Fourier
      transform spectroscopy (DRIFTS). METHOD: Fluconazole polymorphs I and II both
      were prepared by crystallization in dichloromethane. The two forms were
      characterized using differential scanning calorimetry, thermogravimetric
      analysis, powder X-ray diffraction, solubility, and DRIFTS. Transformation of
      polymorph II to polymorph I was also studied under different isothermal
      temperatures using DRIFTS. Kinetic analyses of the data were done using model
      dependent and model-independent methods. Eighteen solid-state reaction models
      were used to interpret the experimental results. RESULTS: Based on statistics,
      the Prout-Tompkins model provided the best fit for the transformation. The
      activation energy (E(a)) value derived from the rate constants of the Prout
      Tompkins model was 329 kJ/mol. Model-independent analysis was also applied to the
      experimental results. The average values calculated using both methods were not
      significantly different. Factors affecting kinetics of transformation such as
      mechanical factors, relative humidity, and the effect of seeding were also
      studied. Mechanical factors, which included trituration and compression, proved
      to enhance transformation rate significantly. Relative humidity proved to
      transform both polymorphs to monohydrate form. The presence of seed crystals of
      polymorph I was proved not to affect the transformation process of polymorph II
      to polymorph I. Effect of solvent of crystallization (dichloromethane) was
      studied. A significant change of the rate of transformation was proved in the
      presence of solvent vapors, and a change on the mechanism was proposed.

PMID- 20050729
TI  - Guest Editor's Comments.

PMID- 20050730
TI  - Different approaches for determination of the attachment degree of polyethylene
      glycols to poly(anhydride) nanoparticles.
AB  - PURPOSE: The aim of the study was to find an appropriate method for determination
      of the attachment degree of polyethylene glycol (PEG) to poly(anhydride)
      nanoparticles. METHODS: The nanoparticles were modified with hydroxy
      functionalized or with amino-functionalized PEGs. Three methods for their
      determination were applied and examined: in particular colorimetry, nuclear
      magnetic resonance ( (1) H-NMR), and elemental analysis (EA). RESULTS: The
      attachment degrees determined by (1) H-NMR and colorimetry were similar. The
      associated amounts of PEGs estimated on the basis of EA differed significantly
      than those determined by colorimetry and (1) H-NMR. CONCLUSION: The colorimetric
      determination was considered fast and simple technique, but (1) H-NMR contributed
      to more precise results.

PMID- 20050731
TI  - The application of modeling techniques to film-coating processes.
AB  - BACKGROUND: The modeling of the processes for film coating of solid dosage forms
      can aid in the prediction and troubleshooting of coating operations. AIM: A
      review of the existing approaches to modeling the coating phenomena was
      undertaken with the aim of identifying key assumptions and limitations of each
      approach. METHOD: Models are categorized into macrolevel and microlevel
      approaches. Macrolevel models can predict mass coating uniformity for a batch of
      solids. On the other hand, microlevel models consider phenomena at the scale of
      the liquid droplets sprayed into the process. Macrolevel models consist either of
      phenomenological approaches, whereby the inherent variabilities in the coating
      process are described by probability distributions. Alternatively, first
      principle models based on rigorous descriptions of solid and gas-phase motion can
      be used to describe the multiphase flow behavior in coating equipment. RESULT:
      The advantages of the rigorous macrolevel approach are that extrapolation of
      results for different operating conditions is more reliable than the
      phenomenological approach and much more information is available about the flow
      of both phases. However, these first-principle models are computationally
      intensive and cannot be used for real-time predictions. On the other hand,
      microlevel models describe chemical and physical phenomena occurring when
      droplets of coating solution impact the surfaces of the solid cores and are
      useful in determining the cause of morphological variations in coating
      properties. CONCLUSIONS: Both micro- and macro-level approaches can be used to
      predict and troubleshoot problems in coating processes. The use of such models in
      the control of coating operations is not widespread but offers significant
      potential to improve quality control.

PMID- 20050732
TI  - Comparative use of Invisalign by orthodontists and general practitioners.
AB  - OBJECTIVE: To test the hypothesis that there is no difference in the use of
      Invisalign between orthodontists and general practitioners. MATERIALS AND
      METHODS: A questionnaire was mailed to all Invisalign providers within a 35-mile
      radius of Stony Brook University. The answers were statistically analyzed. The
      level of significance was set at P < .05. RESULTS: Orthodontists started more
      Invisalign cases (P < .0001). General practitioners started more Invisalign cases
      in the last 12 months (P = .0012). For both groups, the percentage of cases
      started in the last 12 months was inversely related to the number of years
      certified in Invisalign (P < .0001). Significant differences in opinion (P <
      .001) were noted between orthodontists and general practitioners regarding the
      level of experience necessary to treat a Class I malocclusion with a large
      diastema, and whether a Class II subdivision case should be treated with
      Invisalign. CONCLUSION: The hypothesis is rejected. The use of Invisalign by
      orthodontists and general practitioners was compared, and significant differences
      were found.

PMID- 20050733
TI  - Evaluation of CBCT digital models and traditional models using the Little's
      Index.
AB  - OBJECTIVE: To determine if measurements obtained from digital models from cone
      beam computed tomography (CBCT) images were comparable to the traditional method
      of digital study models by impressions. MATERIALS AND METHODS: Digital models of
      30 subjects were used. InVivoDental (Anatomage, San Jose, Calif) software was
      used to analyze CBCT scans taken by a Galileos cone beam scanner (Sirona,
      Charlotte, NC) with a field of view of 15 x 15 x 15 cm(3) and a voxel resolution
      of 0.125 mm. OrthoCAD (Cadent, Fairview, NJ) software was used to analyze
      impression scans of patients at different stages of orthodontic treatment.
      Impressions were taken using alginate and were mailed to OrthoCAD for digital
      conversion. The scans were then electronically returned in digital format for
      analysis. RESULTS: The maxillary mean scores for the Little's Index were 9.65 mm
      for digital models and 8.87 mm for InVivoDental models, respectively. The
      mandibular mean scores for the Little's Index were 6.41 mm for digital models and
      6.27 mm for InVivoDental models, respectively. The mean overjet measurements were
      3.32 mm for digital models and 3.52 mm for InVivoDental models, respectively. The
      overbite measurements were 2.29 mm for digital models and 2.26 mm for
      InVivoDental models, respectively. The paired t-test showed no statistical
      significance between the differences in all measurements. CONCLUSIONS: CBCT
      digital models are as accurate as OrthoCAD digital models in making linear
      measurements for overjet, overbite, and crowding measurements.

PMID- 20050734
TI  - Increased occurrence of dental anomalies associated with infraocclusion of
      deciduous molars.
AB  - OBJECTIVE: To test the null hypothesis that there is no relationship between
      infraocclusion and the occurrence of other dental anomalies in subjects selected
      for clear-cut infraocclusion of one or more deciduous molars. MATERIALS AND
      METHODS: The experimental sample consisted of 99 orthodontic patients (43 from
      Boston, Mass, United States; 56 from Jerusalem, Israel) with at least one
      deciduous molar in infraocclusion greater than 1 mm vertical discrepancy,
      measured from the mesial marginal ridge of the first permanent molar. Panoramic
      radiographs and dental casts were used to determine the presence of other dental
      anomalies, including agenesis of permanent teeth, microdontia of maxillary
      lateral incisors, palatally displaced canines (PDC), and distal angulation of the
      mandibular second premolars (MnP2-DA). Comparative prevalence reference values
      were utilized and statistical testing was performed using the chi-square test (P
      < .05) and odds ratio. RESULTS: The studied dental anomalies showed two to seven
      times greater prevalence in the infraocclusion samples, compared with reported
      prevalence in reference samples. In most cases, the infraoccluded deciduous molar
      exfoliated eventually and the underlying premolar erupted spontaneously. In some
      severe phenotypes (10%), the infraoccluded deciduous molar was extracted and
      space was regained to allow uncomplicated eruption of the associated premolar.
      CONCLUSION: Statistically significant associations were observed between the
      presence of infraocclusion and the occurrence of tooth agenesis, microdontia of
      maxillary lateral incisors, PDC, and MnP2-DA. These associations support a
      hypothesis favoring shared causal genetic factors. Clinically, infraocclusion may
      be considered an early marker for the development of later appearing dental
      anomalies, such as tooth agenesis and PDC.

PMID- 20050735
TI  - Autotransplantation of teeth in 215 patients. A follow-up study.
AB  - OBJECTIVE: To evaluate the success rate of autotransplantation of teeth in
      consecutive patients and to analyze factors affecting the outcome. MATERIALS AND
      METHODS: The subjects consisted of 215 consecutive patients (101 women and 114
      men; aged 9.1-56.4 years, median age 15.2 years [P(10) = 11.4, P(90) = 19.7]) who
      had undergone transplantation of a total of 269 teeth, all by the same surgeon.
      In patients with multiple transplants, only the first transplant was included, to
      ensure that all transplanted teeth were independent units. The transplants were
      recorded as unsuccessful if the tooth had been extracted or was surviving but
      with root resorption or ankylosis. The interval between transplantation and final
      follow-up was a median 4.8 years (P(10) = 2.0, P(90) = 5.5) for successful
      transplants and a median of 2.4 years (P(10) = 0.4, P(90) = 7.7) for unsuccessful
      transplants. RESULTS: One-hundred seventy-five (81%) of the transplantations were
      recorded as successful and 40 (19%) as unsuccessful. Twenty-five teeth had been
      extracted and 15 had survived but did not fulfill the criteria for success.
      CONCLUSIONS: The success rate of 215 consecutively transplanted teeth was 81%.
      The highest success rate was for transplantation of premolars to the maxillary
      incisor region (100%). Complications at surgery such as difficult extraction,
      deviant root anatomy, or damaged root periodontium affected the outcome. During
      growth, a successful transplant preserves alveolar bone.

PMID- 20050736
TI  - Root and bone response to the proximity of a mini-implant under orthodontic
      loading.
AB  - OBJECTIVE: To determine the histological reaction of the root and bone as a mini
      implant approaches the root. MATERIALS AND METHODS: Two kinds of mini-implants
      were inserted into the buccal alveolar bone of 4 beagles (2 males and 2 females).
      The specimens were classified as the near-root group, the PDL contact group, the
      root contact group, and the root perforation group. Cementum resorption, dentin
      resorption, cementum repair, cementum growth, ankylosis, root cracking, and root
      fracture were assessed as the implant neared the root. RESULTS: The incidence of
      root resorption increased when the mini-implant was less than 0.6 mm from the
      root in the near-root group and PDL contact group. Root cracking and root
      fracture occurred in the root contact group and root perforation group. Bone
      resorption and ankylosis were observed in some specimens. However, some specimens
      of the PDL contact group and root contact group had cementum growth or little
      root resorption despite proximity to the root. In the root perforation group,
      root resorption and ankylosis occurred on the side opposite the insertion.
      CONCLUSIONS: There is a risk of root contact and severe tissue damage from a
      thick mini-implant and the drilling procedure, either of which can induce root
      resorption or ankylosis. Use of smaller mini-implants may reduce root contact and
      tissue damage. However, the small mini-implant may need enhancement of its
      stability.

PMID- 20050737
TI  - Ultrastructure of the interface between periodontal tissues and titanium mini
      implants.
AB  - OBJECTIVE: To describe the ultrastructure of the interface between periodontal
      tissues and titanium mini-implants in rat mandibles. MATERIALS AND METHODS: A
      titanium mini-implant was placed between the buccal roots of the mandibular first
      molar of 24 adult rats. After 21, 30, 45, 60, 90, and 120 days of implantation,
      the mandibular portion was removed and fixed in cacodylate-buffered 2%
      glutaraldehyde + 2.5% formaldehyde. The material was decalcified and processed
      for scanning and transmission electron microscopy. RESULTS: Ultrastructural
      analysis revealed a thin cementum-like layer at longer times after implantation
      at the areas in which the periodontal ligament was in contact with the implant.
      CONCLUSIONS: The alveolar bone and the periodontal ligament reorganized their
      constituents around the implant, and a thin cementum-like layer was formed at
      longer times after implantation at the areas in which the periodontal ligament
      was in contact with the implant.

PMID- 20050738
TI  - Cone beam computed tomography for assessment of root length and marginal bone
      level during orthodontic treatment.
AB  - OBJECTIVE: To evaluate the accuracy and precision of cone beam computed
      tomography (CBCT) with regard to measurements of root length and marginal bone
      level in vitro and in vivo during the course of orthodontic treatment. MATERIALS
      AND METHODS: Thirteen patients (aged 12-18 years) from an ongoing study and a dry
      skull were examined with CBCT using multiplanar reformatting for measurements of
      root length and marginal bone level. For in vivo evaluation of changes in root
      length, an index according to Malmgren et al was used, along with a modification
      of this method. RESULTS: The in vitro mean difference between physical and
      radiographic measurements was 0.05 mm (SD 0.75) for root length and -0.04 mm (SD
      0.54) for marginal bone level. In vivo the error was <0.35 mm for root length
      determinations and <0.40 mm for marginal bone level assessments. CONCLUSION:
      Despite changes in tooth positions, the CBCT technique yields a high level of
      reproducibility, enhancing its usefulness in orthodontic research.

PMID- 20050739
TI  - Improved lateral cephalometric superimposition using an automated image fitting
      technique.
AB  - OBJECTIVE: To test the feasibility of automated lateral cephalometric radiograph
      (LCR) superimposition using an image fitting algorithm. MATERIALS AND METHODS:
      Using radiopaque markers, we identified seven cephalometric landmarks on three
      dry skulls, took digital LCRs on each in several rotated positions, and used a
      custom software program (XRay3D) to automatically superimpose each rotated image
      on the initial image using an anterior cranial base reference. We measured
      superimposition error at each landmark and adjusted image brightness levels to
      simulate potential fitting error due to exposure variation. RESULTS: The greatest
      mean error for 24 image rotation trials of less than 10 degrees was less than 0.5
      mm. Rotations of 10 degrees or more were not reliably superimposed. Errors of 0.2
      1.6 mm occurred for +/-10% brightness but increased exponentially with further
      brightness alteration. CONCLUSION: Automated superimposition of LCRs, using this
      fitting technique, has great potential when rotation is less than 10 degrees and
      brightness variation is less than 10%.

PMID- 20050740
TI  - Short-term influence of lingual orthodontic therapy on microbial parameters and
      periodontal status. A preliminary study.
AB  - OBJECTIVE: To perform a preliminary study of the short-term effect of fixed,
      customized lingual orthodontic appliances on periodontal and microbial
      parameters. MATERIALS AND METHODS: The sample comprised 20 subjects (6 males and
      14 females) with a mean age of 22.3 years +/- 8.6 years. Before (T(0)) and 4
      weeks after placement (T(1)) of custom-made lingual appliances on the lower teeth
      only, plaque index (PI), probing pocket depth (PPD), and bleeding on probing
      (BOP) were measured. A 16S rRNA-based polymerase chain reaction (PCR) method was
      used to detect Aggregatibacter actinomycetemcomitans ( Aa ) and Porphyromonas
      gingivalis ( Pg ) in the crevicular fluid. To compare periodontal parameters on
      bonded lingual (testing) and unbonded palatal (control) and labial (control)
      sites between T(0) and T(1), the Wilcoxon test was applied. RESULTS: On the
      lingual aspects of bonded teeth, a significant increase of BOP (T(0): 23.4 +/-
      22.5%; T(1): 46.2 +/- 23.5%; P = .001) and PI (T(0): 0.3 +/- 0.3; T(1): 1.0 +/-
      0.7; P = .001) was observed, but no significant changes for PPD (T(0): 2.1 +/-
      0.4 mm; T(1): 2.2 +/- 0.3 mm; P = .286) were found. On control sites, no
      significant changes were recorded for any periodontal parameter. Aa was found in
      25% of the patients at baseline (5 subjects) and in 35% of the patients at T(1)
      (2 additional positive subjects), whereas Pg was found in 5% of the cohort at
      T(0) and at T(1) (same patient). CONCLUSIONS: Even in the short term, insertion
      of fixed lingual appliances induced a worsening of periodontal parameters
      restricted to bonded lingual sites.

PMID- 20050741
TI  - Treatment effects of twin-block and mandibular protraction appliance-IV in the
      correction of class II malocclusion.
AB  - OBJECTIVE: To evaluate the treatment effects of twin-block and Mandibular
      Protraction Appliance-IV (MPA-IV) in the treatment of Class II division 1
      malocclusion. METHODS: Fifty North Indian girls with Class II division 1
      malocclusion, in the age range of 9-13 years, were chosen. The subjects were
      divided among a control group (n = 10), a twin-block group (n = 25), and an MPA
      group (n = 15). Pre-follow-up and post-follow-up lateral cephalograms of control
      subjects and pretreatment and posttreatment lateral cephalograms of the treatment
      subjects were traced manually and subjected to a pitchfork analysis. RESULTS:
      Neither twin-block nor MPA-IV significantly restricted the forward growth of
      maxilla. Mandibular growth and improvement in the sagittal skeletal relation were
      significantly greater in the twin-block subjects. Distal movement of the
      maxillary dentition and mesial movement of the mandibular dentition were more
      prominent in the MPA-IV subjects. Molar correction and overjet reductions were
      significantly greater in the treatment subjects (P < .001). CONCLUSION: Twin
      block and MPA-IV were effective in correcting the molar relationships and
      reducing the overjet in Class II division 1 malocclusion subjects. However, twin
      block contributed more skeletal effects than MPA-IV for the correction of Class
      II malocclusion.

PMID- 20050742
TI  - Root shortening in patients treated with two-step and en masse space closure
      procedures with sliding mechanics.
AB  - OBJECTIVE: To investigate the comparative amount of root shortening between two
      step and en masse space closure procedures. MATERIALS AND METHODS: Fifty-two
      patients were selected from a pool of patients satisfying the following inclusion
      criteria: no evidence of resorption on the pretreatment panoramic radiographs; no
      dental trauma; no dilacerations of incisor roots, anodontia, or impacted canines;
      complete root formation at the start of treatment; intact and caries-free
      incisors; no endodontically treated incisors; Angle Class I or II malocclusion;
      extraction of four first premolars; and space closure with moderate anchorage.
      Patients received treatment with either a two-step or an en masse procedure to
      close the extraction spaces after alignment and leveling with the same
      preadjusted appliances. Root shortening of the maxillary and mandibular incisors
      was evaluated on panoramic radiographs, taken before and after space closure, and
      measured in millimeters. Distortion of measurements caused by panoramic
      radiographs was corrected by using special metal rods ligated to brackets.
      Statistical comparisons of root shortening between space closure procedures were
      investigated with the two-sample t test. RESULTS: No difference was found in the
      amount of root shortening between space closure procedures. The average root
      shortening of maxillary central and lateral incisors was 0.43 +/- 0.12 mm and
      0.58 +/- 0.10 mm, respectively, and that of mandibular central and lateral
      incisors was 0.23 +/- 0.07 mm and 0.22 +/- 0.06 mm, respectively. CONCLUSION: No
      difference should be expected in root resorption between two-step and en masse
      space closure procedure.

PMID- 20050743
TI  - Comparison of low-intensity pulsed ultrasound and pulsed electromagnetic field
      treatments on OPG and RANKL expression in human osteoblast-like cells.
AB  - OBJECTIVE: To compare two clinically applied treatments to stimulate bone healing
      low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic field (PEMF)
      for their effects on RANKL and OPG expression in osteoblast-like cells in vitro.
      MATERIALS AND METHODS: LIPUS or PEMF was applied to Saos-2 cells for 10 minutes
      or 3 hours. RANKL and OPG expressions were analyzed at 0, 4, 8, or 12 hours after
      treatment with real-time PCR. Secreted protein levels in culture supernatant were
      analyzed at the same posttreatment time points using specific ELISA assays.
      RESULTS: Neither LIPUS nor PEMF had an effect on RANKL protein expression. OPG
      protein was significantly increased by LIPUS after 0 and 4 hours (brief short
      term effect) and was increased almost 2.5-fold by PEMF after 8 hours. The mRNA
      levels of OPG and RANKL were hardly affected by LIPUS treatment at any time
      point. PEMF induced a fivefold increase in RANKL mRNA expression at t = 0. A
      brief PEMF treatment of 10 minutes resulted in downregulation of RANKL expression
      after 0 and 4 hours and upregulation at 12 hours. OPG mRNA was downregulated
      after 8 hours. CONCLUSION: The effects of LIPUS or PEMF expression on OPG and
      RANKL are limited. From our experiments, it seems that LIPUS treatment resulted
      in a quick protein response, while the response of cells to PEMF (3 hours) was
      delayed. The increase in OPG protein at 8 hours post PEMF treatment is indicative
      of reduction of osteolysis.

PMID- 20050744
TI  - Leptin levels in gingival crevicular fluid during orthodontic tooth movement.
AB  - OBJECTIVES: To test if leptin can be detected in the gingival crevicular fluid
      (GCF) around moving teeth, and to determine whether any changes occur during
      orthodontic tooth movement. MATERIALS AND METHODS: An upper canine requiring
      distal movement served as the test tooth; the contralateral canine was used as a
      control tooth. The control tooth was included in the orthodontic appliance, but
      was not subjected to the orthodontic force. GCF sampling from the distal sites of
      the test and control teeth was done at baseline, 1 hour, 24 hours, and 168 hours.
      RESULTS: Leptin concentrations of the test teeth decreased in a time-dependent
      manner. When compared with the baseline measurement, the decrease was significant
      at 168 hours (P < .05). CONCLUSIONS: The concentration of leptin in GCF is
      decreased by orthodontic tooth movement; the results of the present study also
      suggest that leptin may have been one of the mediators responsible for
      orthodontic tooth movement.

PMID- 20050745
TI  - Caries risk factors in children under treatment with sectional brackets.
AB  - OBJECTIVE: To longitudinally investigate the caries risk levels in children
      undergoing orthodontic treatment with sectional brackets. MATERIALS AND METHODS:
      A total of 42 children scheduled for orthodontic treatment with sectional
      orthodontic appliances participated in this study. They were divided into two
      groups based on decayed, missing, and filled permanent and deciduous teeth
      (DMFT/dmft) scores and counts of mutans streptococci (MS) prior to treatment. One
      was the low caries risk group (n = 26) and the other was the high caries risk
      group (n = 16). Paraffin-stimulated whole saliva was collected for examination of
      salivary flow rate, buffer capacity, and MS and lactobacilli (LB) levels before
      treatment, 2 and 4 months after appliance placement, and 2, 4, and 8 months after
      appliance removal. RESULTS: The pretreatment salivary flow rates, buffer
      capacity, and MS levels remained statistically unchanged during and after active
      orthodontic treatment in both groups. The levels of LB in the high caries risk
      group were significantly elevated by appliance placement, but upon appliance
      removal started to fall significantly and came a little short of the pretreatment
      levels. In the low caries risk group, the pretreatment levels of LB remained
      statistically unchanged during and after treatment. There were no significant
      differences in salivary flow rate or buffer capacity, but there were significant
      differences in MS and LB scores between the two groups at every measurement time.
      CONCLUSIONS: In children undergoing orthodontic treatment with sectional
      brackets, LB levels are an important part in making caries risk assessment.

PMID- 20050746
TI  - Young people's esthetic perception of dental midline deviation.
AB  - OBJECTIVE: To test the hypothesis that young people's esthetic perception of
      dentition midline deviation or the threshold below which they find the deviation
      "acceptable" depends on the gender and face type of the person with the deviation
      and the gender of the evaluator. MATERIALS AND METHODS: Facial images of six
      young subjects with three different face types were captured, and their dentition
      midlines were altered digitally. The images were evaluated by young people with
      no dental training. Statistical analysis was carried out to determine the
      threshold for acceptable dentition midline deviation and factors influencing
      perception. RESULTS: The mean value for the threshold below which a deviation was
      judged "acceptable" was 2.403 mm (95% confidence interval, 2.315-2.491). The
      preferences of evaluators did not significantly depend on the direction of the
      deviation. Both male and female evaluators were significantly less tolerant of
      deviation in female subjects than in male subjects. However, female evaluators
      were significantly more tolerant of midline deviations in male subjects than were
      male evaluators. In addition, the same degree of deviation was most noticeable in
      male subjects with a tapered face type and least noticeable in female subjects
      with a square face type. CONCLUSIONS: The gender and face type of an individual
      with dentition midline deviation and the gender of the evaluator do affect young
      people's esthetic perception of a dentition midline deviation and the threshold
      below which they find the deviation "acceptable."

PMID- 20050747
TI  - Debris, roughness and friction of stainless steel archwires following clinical
      use.
AB  - OBJECTIVE: To investigate the degree of debris, roughness, and friction of
      stainless steel orthodontic archwires before and after clinical use. MATERIALS
      AND METHODS: For eight individuals, two sets of three brackets (n = 16) each were
      bonded from the first molar to the first premolar. A passive segment of 0.019- x
      0.025-inch stainless steel archwire was inserted into the brackets and tied by
      elastomeric ligature. Debris level (via scanning electron microscopy), roughness,
      and frictional force were evaluated as-received and after 8 weeks of intraoral
      exposure. Mann-Whitney, Wilcoxon signed-rank, and Spearman correlation tests were
      used for statistical analysis at the .05 level of significance. RESULTS: There
      were significant increases in the level of debris (P = .0004), roughness of
      orthodontic wires (P = .002), and friction (P = .0001) after intraoral exposure.
      Significant positive correlations (P < .05) were observed between these three
      variables. CONCLUSION: Stainless steel rectangular wires, when exposed to the
      intraoral environment for 8 weeks, showed a significant increase in the degree of
      debris and surface roughness, causing an increase in friction between the wire
      and bracket during the mechanics of sliding.

PMID- 20050748
TI  - Clinical outcomes of 0.018-inch and 0.022-inch bracket slot using the ABO
      objective grading system.
AB  - OBJECTIVE: To determine if there is a significant difference in the clinical
      outcomes of cases treated with 0.018-inch brackets vs 0.022-inch brackets
      according to the American Board of Orthodontics (ABO) Objective Grading System
      (OGS). MATERIALS AND METHODS: Treatment time and the ABO-OGS standards in
      alignment/rotations, marginal ridges, buccolingual inclination, overjet, occlusal
      relationships, occlusal contacts, interproximal contacts, and root angulations
      were used to compare clinical outcomes between a series of 828 consecutively
      completed orthodontic cases (2005-2008) treated in a university graduate
      orthodontic clinic with 0.018-inch- and 0.022-inch-slot brackets. RESULTS: A two
      sample t-test showed a significantly shorter treatment time and lower ABO-OGS
      score in four categories (alignment/rotations, marginal ridges, overjet, and root
      angulations), as well as lower total ABO-OGS total score, with the 0.018-inch
      brackets. The ANCOVA-adjusting for covariants of discrepancy index, age, gender,
      and treatment time-showed that the 0.018-inch brackets scored significantly lower
      than the 0.022-inch brackets in both the alignment/rotations category and total
      ABO-OGS score. CONCLUSIONS: There were statistically, but not clinically,
      significant differences in treatment times and in total ABO-OGS scores in favor
      of 0.018-inch brackets as compared with the 0.022-inch brackets in a university
      graduate orthodontic clinic (2005-2008).

PMID- 20050749
TI  - Tongue pressure changes before, during and after crib appliance therapy.
AB  - OBJECTIVE: To describe tongue pressure changes before, during, and after crib
      appliance therapy in mixed dentition open bite cases. MATERIALS AND METHODS: A
      crib appliance was applied to each of the 13 patients in the study group. The
      control group consisted of six patients. Tongue pressures were measured using a
      diaphragm-type pressure transducer during rest position and swallowing in
      changing intervals for 12 months in both groups. Tongue pressures were performed
      on the upper first molar, upper and lower central incisors, and on the middle
      spur of the crib appliance. RESULTS: In the study group, the initial resting
      tongue pressure on the upper molar increased after appliance insertion and was
      followed by a decreasing trend for 12 months. The resting tongue pressures on the
      upper and lower incisors remained lower than initial values at the end of 12
      months. Swallowing pressures returned to initial values at the end of 12 months,
      and the changes were insignificant. The resting and swallowing tongue pressures
      on the middle spur of the crib appliance decreased gradually during the 10 months
      (P < .05). Pressure changes in the control group were insignificant for all
      measurements. Open bite values in the study group increased significantly by the
      end of 12 months. CONCLUSIONS: Measurements performed on the crib confirm the
      tongue adaptation to environmental changes. Resting tongue pressures at the 12th
      month remained lower than the initial values. These findings indicate adaptive
      behavior of the tongue to open bite closure and the new position of the incisors.

PMID- 20050750
TI  - Effects of occlusal contact and its area on gravity fluctuation.
AB  - OBJECTIVE: To examine changes in gravity fluctuation caused by experimentally
      altering the area of occlusal contact. MATERIALS AND METHODS: Subjects consisted
      of 15 adult Japanese males with normal stomatognathic function, no missing teeth
      except for the third molars, and equivalent occlusal contact in the anterior and
      bilateral posterior regions. Silicon biteplates fabricated for each subject to
      evaluate gravity fluctuation in relation to changes in occlusal contact area were
      as follows: RP(-)-OC(+) (entire occlusal surface covered in centric occlusion);
      RP(+)-OC(+) (entire occlusal surface covered with bite slightly raised); Ant or
      Pos/RP(+)-OC(+) (anterior or posterior region selectively covered); and RP(+)-OC(
      ) (only retromolar pads covered, no occlusal coverage). RESULTS: No significant
      differences in gravity fluctuation were noted between subjects wearing biteplates
      covering the entire occlusal surface. Subjects wearing biteplates with no
      occlusal contact showed greater gravity fluctuation than those with occlusal
      contact. In addition, gravity fluctuation for the Ant/RP(+)-OC(+) group (no
      occlusal contact in the posterior region) was greater than for RP(+)-OC(+) and
      Pos/RP(+)-OC(+). However, groups with unilateral occlusal contact in the
      posterior region exhibited large right and left sway amplitude. CONCLUSIONS:
      These results suggest that occlusal contact, especially posterior occlusal
      contact, affects gravity fluctuation, and that appropriate occlusion attained by
      maintaining even occlusal contact in the posterior region is crucial for gravity
      fluctuation.

PMID- 20050751
TI  - Corrosion resistance of different nickel-titanium archwires in acidic fluoride
      containing artificial saliva.
AB  - OBJECTIVE: To test the hypothesis that different nickel-titanium (NiTi) archwires
      may have dissimilar corrosion resistance in a fluoride-containing oral
      environment. MATERIALS AND METHODS: Linear polarization test, a fast
      electrochemical technique, was used to evaluate the corrosion resistance, in
      terms of polarization resistance (R(p)), of four different commercial NiTi
      archwires in artificial saliva (pH 6.5) with various NaF concentrations (0%,
      0.01%, 0.1%, 0.25%, and 0.5%). Two-way analysis of variance was used to analyze
      R(p) with the factors of archwire manufacturer and NaF concentration. Surface
      characterizations of archwires were analyzed using scanning electron microscopy,
      atomic force microscopy, and x-ray photoelectron spectroscopy. RESULTS: Both
      archwire manufacturer and NaF concentration had a significant influence on R(p)
      of NiTi archwires. Different surface topography was present on the test NiTi
      archwires that contained the similar surface chemical structure (TiO(2) and trace
      NiO). The surface topography did not correspond to the difference in corrosion
      resistance of the NiTi archwires. Increasing the NaF concentration in artificial
      saliva resulted in a decrease in R(p), or corrosion resistance, of all test NiTi
      archwires. The NiTi archwires severely corroded and showed similar corrosion
      resistance in 0.5% NaF-containing environment. CONCLUSIONS: Different NiTi
      archwires had dissimilar corrosion resistance in acidic fluoride-containing
      artificial saliva, which did not correspond to the variation in the surface
      topography of the archwires. The presence of fluoride in artificial saliva was
      detrimental to the corrosion resistance of the test NiTi archwires, especially at
      a 0.5% NaF concentration.

PMID- 20050752
TI  - The essential work of fracture of thermoplastic orthodontic retainer materials.
AB  - OBJECTIVE: To investigate whether oral cleansing agents affect the essential work
      of fracture (EWF) and plastic work of fracture (PWF) for two types of orthodontic
      thermoplastic retainer materials. MATERIALS AND METHODS: Polyethylene
      terephthalate-glycol (PETG; Tru-Tain Splint) and polypropylene/ethylene-propylene
      rubber (PP-EPR) blend (Essix-C+) sheets were compared. For each material, six
      sets of 25 sheets were thermoformed into double-edge-notched-tension specimens;
      subsets of five specimens were formed with internotch distances (L) equal to 6,
      8, 10, 12, or 14 mm, respectively. Sets were stored (160 hours, 25 degrees C) in
      air (DRY), distilled water (DW), Original Listerine (LIS), mint Crest ProHealth
      (CPH), 3% hydrogen peroxide (HP), or Polident solution (POL). Specimens were
      fractured in tension at 2.54 mm/min. Areas under load-elongation curves were
      measured to determine total work of fracture (W(f)). Linear regressions (W(f) vs
      L [n = 25]) yielded intercepts (EWF) and slopes (PWF). Ninety-five percent
      confidence intervals were used to evaluate differences in EWF and PWF estimates.
      RESULTS: PP-EPR blends showed higher EWFs after storage in HP vs storage in DW.
      PP-EPR blend showed higher EWFs after storage in CPH vs PETG. After HP storage,
      PP-EPR exhibited lower PWFs than with any other storage conditions. PP-EPR
      exhibited higher PWFs than PETG after storage in DRY, DW, and LIS. CONCLUSIONS:
      Compared with DW, none of the cleansers decreased the energy to initiate
      fracture. With one exception, no cleanser decreased the energy to continue
      plastic fracture extension. In PP-EPR blend, increased resistance to fracture
      initiation was observed with CPH and HP, yet, surprisingly, HP decreased
      resistance to plastic fracture growth.

PMID- 20050753
TI  - Influence of natural bovine enamel roughness on bond strength after etching.
AB  - OBJECTIVE: To determine and compare the longitudinal and transverse roughness
      parameters of the enamel surface of bovine teeth and evaluate the influence of
      these parameters on bond strength. MATERIALS AND METHODS: Ninety bovine incisors
      were used. The surface roughness of enamel was measured with a profilometer. For
      each tooth, five readings were taken in the longitudinal plane and five were
      taken in the transverse plane of the long axis of the tooth in an area equal to
      the size of the bracket base. The metal brackets were bonded with Transbond XT,
      and bond strength was evaluated in a universal test machine. RESULTS: There was a
      statistical correlation (P < .01) between the longitudinal and transverse
      roughness measurements. There was no correlation between roughness measurements
      (longitudinal and transverse) and bond strength (P > .05), nor was there a
      correlation between total roughness (longitudinal Ra and transverse Ra) and bond
      strength. The Student's t-test showed that there was a statistically significant
      difference (P < .05) between longitudinal and transverse roughness. CONCLUSION:
      The transverse roughness is greater than the longitudinal roughness, there is a
      strong correlation between longitudinal and transverse roughness, and there is no
      correlation between enamel roughness and bond strength.

PMID- 20050754
TI  - Plant extract ankaferd blood stopper effect on bond strength.
AB  - OBJECTIVE: To determine the effect of Ankaferd Blood Stopper (ABS) on the shear
      bond strength (SBS) of orthodontic attachments. MATERIALS AND METHODS: The study
      material consisted of 60 freshly extracted bovine permanent mandibular incisor
      teeth. All teeth were cleaned and randomly divided into three groups of 20
      specimens and etched with 37% phosphoric acid for 15 seconds, washed, and air
      dried. Teeth in groups 1 and 2 were contaminated with ABS and blood,
      respectively. Teeth in group 3 were only air-dried. Roth Generous maxillary
      central incisor brackets were bonded with Transbond XT to all teeth. SBS was
      applied using a universal test machine. The one-way analysis of variance (ANOVA)
      test was used to determine significant differences in SBS between the three
      groups, and Tukey honestly significant post hoc test was used to compare
      subgroups. RESULTS: The mean bond strengths and standard deviations of groups 1,
      2, and 3 were 9.58 +/- 0.95, 4.04 +/- 0.69, and 19.56 +/- 1.84 MPa, respectively.
      CONCLUSIONS: Specimens contaminated with blood showed a statistically significant
      lower in vitro SBS than those contaminated with ABS. ABS may be used clinically
      for obtaining a blood-free tooth surface during application of the brackets on
      surgically exposed, impacted teeth.

PMID- 20050755
TI  - Self-ligating brackets in orthodontics. A systematic review.
AB  - OBJECTIVE: To evaluate the clinical differences in relation to the use of self
      ligating brackets in orthodontics. MATERIALS AND METHODS: Electronic databases
      were searched; no restrictions relating to publication status or language of
      publication were applied. Randomized controlled trials (RCTs) and controlled
      clinical trials (CCTs) investigating the influence of bracket type on alignment
      efficiency, subjective pain experience, bond failure rate, arch dimensional
      changes, rate of orthodontic space closure, periodontal outcomes, and root
      resorption were selected. Both authors were involved in study selection, validity
      assessment, and data extraction. Disagreements were resolved by discussion.
      RESULTS: Six RCTs and 11 CCTs were identified. Meta-analysis of the influence of
      bracket type on subjective pain experience failed to demonstrate a significant
      advantage for either type of appliance. Statistical analysis of other outcomes
      was unfeasible because of inadequate methodological design and heterogenous
      designs. CONCLUSIONS: At this stage there is insufficient high-quality evidence
      to support the use of self-ligating fixed orthodontic appliances over
      conventional appliance systems or vice versa.

PMID- 20050756
TI  - Multiple endocrine neoplasia-2B presenting with orthodontic relapse.
AB  - The multiple endocrine neoplasia (MEN) syndromes are a relatively uncommon group
      of genetic disorders characterized by the development of tumors in various
      endocrine organs. MEN type 2B is of particular interest to the dental profession
      because of its oral manifestations, which are often some of the earliest
      clinically detectable signs of the disorder. Early identification of this
      syndrome is critical because affected patients often develop a characteristic
      malignancy, medullary carcinoma of the thyroid, at a very early age. We describe
      a 17-year-old male whose initial diagnosis of MEN-2B was triggered by his
      orthodontist's request for an oral and maxillofacial pathology consultation to
      evaluate the patient's oral abnormalities.

PMID- 20050757
TI  - Location and presence of permanent teeth in a complete bilateral cleft lip and
      palate population.
AB  - OBJECTIVE: To describe the location and presence of permanent teeth in
      nonsyndromic complete bilateral cleft lip and palate patients from the Manitoba
      Centre for Craniofacial Difference. MATERIALS AND METHODS: Records of 1570
      patients dating back to 1958 were assessed in this retrospective chart review.
      RESULTS: Thirty-eight patients met the inclusion criteria, providing 76 cleft
      site teeth: A tooth on each side of the cleft was considered to have developed
      from a single lateral incisor tooth bud. The pattern M was assigned when a tooth
      was found mesial to the cleft, D when distal, MD when mesial and distal and AB if
      none was found. Pattern M was noted 9.2% of the time; D, 47.4%; MD, 5.3%; and AB,
      38.2%. Teeth outside the cleft site: In the maxilla, agenesis occurred in 11.9%
      of second premolars and 10.5% of central incisors. In the mandible, agenesis
      occurred in 4.0% of second premolars, 2.6% of lateral incisors, 2.6% of central
      incisors, and 2.6% of second molars. CONCLUSIONS: The lateral incisor was most
      commonly found distal to the cleft. Agenesis of the lateral incisor and teeth
      outside the cleft were more common than in noncleft populations.

PMID- 20050758
TI  - Rapid tooth movement and orthodontic treatment using dentoalveolar distraction
      (DAD). Long-term (5 years) follow-up of a Class II case.
AB  - The purpose of this report is to describe the dentoalveolar distraction (DAD)
      technique and to present its effects on the surrounding structures by presenting
      a Class II case. A 15-year-old skeletal and dental Class II female patient with
      an overjet of 9 mm was treated by DAD osteogenesis. A custom-made, rigid, tooth
      borne intraoral distraction device was used for rapid canine retraction.
      Osteotomies surrounding the canines were made to achieve rapid movement of the
      canines within the dentoalveolar segment, in compliance with distraction
      osteogenesis principles. The amount of canine retraction was 7.5 mm in 12 days at
      a rate of 0.625 mm per day, with no posterior anchorage loss. The canine teeth
      showed 1.6 mm extrusion and 11 degrees inclination change (distal tipping) during
      the same period. Orthodontic treatment continued for 6 months with no clinical
      and radiographic evidence of complications such as root fracture, root
      resorption, ankylosis, and soft tissue dehiscence. The DAD technique is an
      innovative method, because it reduces overall orthodontic treatment time by about
      50%, with no unfavorable effects on periodontal tissues and surrounding
      structures and with no need to use any intraoral or extraoral anchorage
      appliances.

PMID- 20050759
TI  - The platelet functions in patients with ankylosing spondylitis: anti-TNF-alpha
      therapy decreases the mean platelet volume and platelet mass.
AB  - The present study was designed to investigate the interaction between platelet
      indices (mean platelet volume (MPV), platelet count (PLC) and platelet mass
      (PLM)), inflammatory markers and disease activity in ankylosing spondylitis (AS)
      subjects. The effects of anti-TNF-alpha therapy and conventional treatment on
      platelet indices were also compared. We studied 68 patients with AS (group I, 46
      men, age: 36.4 +/- 6.9 years) and as control group 34 age and sex-matched healty
      subjects. All patients received conventional therapy (CT) at the beginning (Group
      I). The patients were reevaluated after 3 months according to Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI) score. Group II consisted of 35
      subjects who responded to the CT and continued to take the same therapy for 3
      months additionally. Group III consisted of 33 subjects who had a high disease
      activity score (BASDAI > 4) after 3 months and were accepted refractory to the CT
      therapy. In Group III the treatment was switched to infliximab and continued for
      3 months at the standard intravenous dose. Significantly higher baseline MPV, PLC
      and PLM was reported as compared to controls decreased by therapy (9.12 +/- 1.20
      vs. 8.35 +/- 0.94 fl, p < 0.001, 340 +/- 69 vs. 251 +/- 56 (x 10(3)/ microL) p <
      0.0001, 3096 +/- 736 vs. 2110 +/- 384; p < 0.0001, respectively). In the same
      way, they were substantially lowered by both treatments in group II and group
      III. PLC and PLM were positively correlated with WBC and ESR (r : 0.44; p <
      0.0001, r : 0.41; p = 0.001, r : 0.52; p < 0.0001, r : 0.41; p = 0.001),
      respectively) in AS patients. Additionally, MPV and PLM were positively
      correlated with BASDAI score (r : 0.41; p < 0.001, r = 0.29; p < 0.001
      respectively). We have found that increased platelet activity reduced by therapy
      in AS patients. Additionally, it was correlated with inflammatory markers and
      disease activity. According to these results, it can be suggested that both anti
      TNF-alpha and conventional therapy might contribute to a decrease in the risk of
      cardiovascular morbidity and mortality in AS patients.

PMID- 20050760
TI  - The platelet indices in patients with rheumatoid arthritis: mean platelet volume
      reflects disease activity.
AB  - The present study was designed to investigate the interaction between platelet
      indices, inflammatory markers and disease activity in rheumatoid arthritis (RA)
      subjects. The effects of anti-TNF-alpha therapy and conventional treatment on
      platelet indices were also compared. We studied 97 patients with RA (19 men, 78
      women: mean age 51 years) and 33 age and sex-matched healthy subjects as a
      control group. All RA patients were administered conventional therapy. After 3
      months of therapy, 35 subjects who had high disease activity score (DAS28 > 5.1)
      were grouped as non-responders and were administered infliximab as a TNF-alpha
      blocker at the standard intravenous dose. Responders to the conventional therapy
      and non-responders were also compared. At baseline white blood cell (WBC),
      erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet count
      and mean platelet volume (MPV) were significantly higher in patients with RA.
      Mean platelet volume was positively correlated with DAS28 score (r = 0.27; p =
      0.007). These markers of inflammation and platelet indices were substantially
      decreased after therapy. The reductions were similar in responders to
      conventional therapy and non-responders (TNF alpha group). In conclusion, we
      found that MPV was correlated with inflammatory markers and disease activity in
      patients with RA. Both anti-TNF-alpha and conventional therapy decreases markers
      of inflammation and platelet indices. MPV can reflect both disease activity and
      response to treatment.

PMID- 20050761
TI  - Platelet-derived microparticle levels are significantly elevated in patients
      treated by elective stenting compared to subjects with diagnostic catheterization
      alone.
AB  - Significant platelet reactivity with endothelial damage may occur during
      percutaneous coronary intervention such as balloon angioplasty and elective
      stenting in patients with stenotic or occluded arteries in coronary artery
      disease. Activated platelets express several surface epitopes to aggregate and
      form heterotypic interactions with leukocytes and endothelial cells, secrete
      biomarkers to enhance their prothrombotic properties and also generate increased
      level of microparticles (PMPs). These events may contribute to subacute stent
      thrombosis induced by the procedure-mediated trauma. Our aim was to study the
      level of PMPs and other platelet activation markers at an early time point after
      stenting with bare metal stent in patients on aspirin antiplatelet pre-treatment,
      and these results were compared to data obtained from subjects with diagnostic
      catheterization alone. We found that at 15 minutes after the completion of
      stenting, the levels of PMPs (557 +/- 83/microl versus 325 +/- 42/microl), the
      platelet P-selectin expression (2.7 +/- 0.3% versus 1.99 +/- 0.1%) and the ratio
      of platelet-monocyte heterotypic aggregates (48 +/- 4% versus 38 +/- 3%) were
      significantly (p < 0.05) elevated in patients compared to unstented subjects, but
      no difference was found in soluble P-selectin values. We suggest that the
      observed cellular changes are early and sensitive markers to detect the platelet
      activating effect of stent implantation.

PMID- 20050762
TI  - Assessment of reperfusion following thrombolysis with mean fibrillation and
      amplitude spectrum area in patients with sustained ventricular fibrillation.
AB  - BACKGROUND: Improved microcirculatory reperfusion in patients with ventricular
      fibrillation (VF) enhances the electrical activity of the fibrillation process
      and increases the likelihood of successful defibrillation. METHODS: Changes in
      amplitude spectrum area (AMSA) and mean fibrillation (MF) in patients with
      sustained VF were analysed after administration of rt-PA variant tenecteplase in
      out-of-hospital cardiac arrest (OHCA) during cardiopulmonary resuscitation (CPR).
      RESULTS: A total of 69 ECG sequences from nine patients were evaluated. Patients
      who received tenecteplase showed significantly longer duration of VF (p = 0.016).
      While AMSA declined significantly during CPR (p = 0.001), MF did not differ
      between groups. There were two survivors in the treatment group and one in the
      control group. CONCLUSION: When tenecteplase was administered during CPR, VF
      lasted significantly longer than in controls. Changes in MF and AMSA did not
      indicate improved myocardial perfusion in patients who received tenecteplase
      during CPR.

PMID- 20050763
TI  - Aldosterone stimulates the proliferation of uterine leiomyoma cells.
AB  - OBJECTIVE: Although uterine leiomyomas are the most common gynaecological benign
      tumour and greatly affect reproductive health and well being, the pathophysiology
      and epidemiology of uterine leiomyomas are not well known. Elevated blood
      pressure has an independent, positive association with risk for clinically
      detected uterine leiomyomas. Aldosterone is a key biological peptide in the renin
      angiotensin-aldosterone system that regulates blood pressure. In this study, we
      investigated the siginificant stimulatory effect of aldosterone on leiomyoma
      cells proliferation. STUDY DESIGN: This study investigated the potential role of
      aldosterone in the proliferation of ELT-3 leiomyoma cells. RESULTS: Aldosterone
      induced ELT-3 leiomyoma cell proliferation and the expression of
      mineralocorticoid receptor (MR) were confirmed. Pre-incubating the cells with the
      MR blockers spironolactone or eplerenone effectively repressed aldosterone
      induced and angiotensin II (Ang II)-induced cell proliferation. Treatment of
      aldosterone increased the levels of Ang II type-1 receptor mRNA. CONCLUSION:
      These experimental findings in vitro show the presence of complex regulation of
      Ang II and aldosterone induced leiomyoma cell proliferation.

PMID- 20050764
TI  - Gabapentin vs. low-dose transdermal estradiol for treating post-menopausal women
      with moderate to very severe hot flushes.
AB  - BACKGROUND: Gabapentin (GPT), a widely used drug in neurology, has been proposed
      as a non-hormonal option for the management of hot flushes in menopausal women
      with contraindications for estrogen therapy. OBJECTIVE: To compare GPT versus low
      dose transdermal estradiol (E(2)) for treating post-menopausal women with
      moderate to very severe hot flushes. METHODS: A total of 45 post-menopausal women
      with moderate to very severe hot flushes were prospectively and single-blinded
      randomised to receive oral GPT 600 mg/night or transdermal 25 microg/day E(2) per
      week. Hot flush intensity and frequency were assessed with the Menopause Rating
      Scale and a numeric scale respectively at baseline and at 1, 4 and 8 weeks. Side
      effects were also assessed. RESULTS: Hot flush intensity and frequency
      significantly decreased for both groups at 1, 4 and 8 weeks of treatment as
      compared to baseline; however, this decrease was statistically more evident for
      the E(2) group. Although the percentage of hot flush intensity and frequency
      reduction at the end of the treatment was higher for E2, this was not
      statistically significant (68.2% vs. 60.6% for intensity and 70.1% vs. 58.9% for
      frequency, respectively, p > 0.05, NS). Encountered side effects included:
      drowsiness, dizziness, fatigue (GPT group) and mastodynia, vaginal spotting and a
      local allergic reaction (E(2) group). Compliance to treatment was 95.6% (GPT
      group) as compared to 90.9% for the E(2) group. CONCLUSION: Despite statistical
      significant differences, from a clinical point of view oral GPT 600 mg was as
      effective as low-dose transdermal E(2) in controlling moderate to severe hot
      flushes in post-menopausal women, and should be recommended as an alternative
      option in those with contraindications to estrogen therapy. More research is
      warranted in this regard.

PMID- 20050765
TI  - Relation between first trimester maternal serum leptin levels and body mass index
      in normotensive and pre-eclamptic pregnancies--role of leptin as a marker of pre
      eclampsia: a prospective case-control study.
AB  - OBJECTIVE: We measured first trimester plasma leptin concentrations in 37 women
      who subsequently developed pre-eclampsia and 53 normotensive controls to
      determine the interrelation between leptin and body mass index (BMI) in both
      groups. We further investigated the association between the risks for pre
      eclampsia with maternal leptin levels. METHODS: Bloods samples were collected at
      13 weeks. Non-parametric tests, Spearman's correlation, linear regression
      analysis and multiple logistic regression analysis were applied in our data.
      RESULTS: 1 kg/m(2) increase in pre-pregnancy BMI was related to a 2.747 (95% CI:
      3.242-2.252) ng/ml rise in leptin concentration among cases and 2.502 (95% CI:
      2.873-2.131) ng/ml rise in leptin concentrations among controls. Increased leptin
      concentration (>or=25.3 ng/ml ) in lean women is associated with a 18.8-fold
      increased risk of pre-eclampsia (adjusted OR: 18.8, CI: 1.8-194, p = 0.014 ).
      Leptin treated as a continuous variable is a significant predictor of pre
      eclampsia (adjusted OR: 1.08, CI: 1.018-1.133, p = 0.009). CONCLUSION: Increased
      leptin concentration can definitely contribute to the prediction of pre-eclampsia
      in lean women, but this is not the case in overweight women. Further research in
      terms of longitudinal case-control studies is required to clarify the predictive
      value of pre-eclampsia.

PMID- 20050766
TI  - The effects of transdermal contraception on lipid profiles, carbohydrate
      metabolism and coagulogram in Thai women.
AB  - OBJECTIVE: To evaluate the effects of the contraceptive patch on lipid profiles,
      carbohydrate metabolism and coagulogram in Thai women. METHODS: Fifty healthy
      Thai women were assigned to use contraceptive patches. Blood chemistries test
      including liver function test, lipid profiles and coagulogram were evaluated at
      baseline, cycles 3 and 6. RESULTS: Total cholesterol, triglyceride and HDL were
      significantly increased, whereas LDL was slightly decreased. The ratio of total
      cholesterol/HDL and LDL/HDL significantly decreased when applying the patch.
      After discontinued use of contraceptive patch, the women whose blood tests
      present hypercholesterol during patch use showed a continuous decrease in blood
      results of total cholesterol level over 3 months. Moreover, mean fasting glucose,
      SGOT, SGPT and alkaline phosphate were decreased. No woman suffering from VTE in
      this study. CONCLUSIONS: The use of contraceptive patch does not exert a negative
      effect on carbohydrate metabolism, lipid profile, liver function test and blood
      coagulogram. However, further studies are required to elucidate the effect of the
      contraceptive on the patch user in long term.

PMID- 20050767
TI  - Polycystic ovary syndrome: a biopsychosocial understanding in young women to
      improve knowledge and treatment options.
AB  - AIM: To assess psychological features in young women with and without PCOS.
      METHODS: Observational, cross-sectional pilot study in young women aged 18-25
      with (n = 24) or without (n = 22) PCOS (age: 22.41 +/- 0.39 vs. 21.95 +/- 0.47
      years, p = 0.46; BMI: 29.17 +/- 1.54 vs. 22.05 +/- 0.83 kg/m(2), p = 0.0003). The
      main outcome measures were quality of life, anxiety, depression, risk perception
      and fears on future health. RESULTS: Women with PCOS demonstrated worsened
      quality of life (p = 0.033) and greater anxiety (p = 0.01) and depression (p =
      0.023) than women without PCOS related to BMI status. Women with PCOS were more
      likely to perceive themselves as at risk of obesity (p = 0.012) and infertility
      (p < 0.0001), and perceived greater importance in reducing future risk of
      prediabetes (p = 0.027), gestational diabetes (p = 0.039), type 2 diabetes (p =
      0.01), heart disease (p = 0.005), obesity (p = 0.0007) and infertility (p =
      0.023) than women without PCOS. Women with PCOS were more likely to have fears
      about future health related to weight gain (p = 0.045), loss of femininity (p =
      0.035), loss of sexuality (p = 0.003) and infertility (p = 0.019) than women
      without PCOS. CONCLUSIONS: Worsened quality of life, anxiety and depression in
      young women with PCOS is related to BMI. Risk perception is appropriately high in
      PCOS, yet perceived risks of future metabolic complications are less common than
      those related to weight gain and infertility.

PMID- 20050768
TI  - Distribution and abundance of parasites of the rhodesgrass mealybug, Antonina
      graminis: reassessment of a classic example of biological control in the
      Southeastern United States.
AB  - Control of the rhodesgrass mealybug, Antonina graminis Maskell (Hemiptera:
      Pseudococcidae), by the encyrtid wasp Neodusmetia sangwani is considered a
      textbook example of classical biological control. However, recent evidence
      suggests that A. graminis is abundant in the southeastern United States and no
      recent surveys have been conducted to determine the status of N. sangwani or
      other A. graminis parasites. A survey was conducted and it was found that N.
      sangwani was uncommon overall, occurring at only 20 percent of survey sites. In
      addition, N. sangwani exhibited a patchy geographic distribution. Possible causes
      for these results are that N. sangwani has not dispersed widely since its
      introduction, or that the imported fire ant, Solenopsis invicta, is interfering
      with biological control. These results suggest that a reevaluation of the
      efficacy of biological control may be necessary. The survey also found two other
      encyrtid wasps utilizing A. graminis as a host. One, Acerophagus sp., is
      apparently native and was nearly as frequent as N. sangwani, while the other,
      Pseudectroma sp., is apparently introduced and relatively rare.

PMID- 20050769
TI  - Impact of darker, intermediate and lighter phenotypes of body melanization on
      desiccation resistance in Drosophila melanogaster.
AB  - A possible link between melanization and desiccation resistance can be inferred
      if within population differences in melanization find significant correlations
      with desiccation resistance and its mechanistic basis i.e. rate of water loss/hr.
      Accordingly, darker, intermediate and lighter phenotypes of body melanization
      were analyzed in wild and laboratory reared Drosophila melanogaster L. (Diptera:
      Clyclorrapha) populations from highland and lowland sites located in close
      proximity at five different latitudinal locations (11.15 degrees N to 31.06
      degrees N) within the Indian subcontinent. In large population samples,
      occurrence of significant within population variability made it possible to
      assort non-overlapping phenotypes of body coloration (i.e. lighter (< 25%),
      intermediate (30 to 40%) and darker (> 45%)) for all the populations which were
      further investigated for desiccation resistance and rate of water loss/hr.
      Significantly, higher desiccation resistance but much reduced rate of water
      loss/hr were observed in darker and intermediate phenotypes in all the
      populations. By contrast, lighter phenotypes exhibited lower desiccation
      tolerance but higher rate of water loss/hr. A regression analysis between traits
      provided similar slope values for wild and laboratory populations. For all three
      physiological traits, predicted trait values from multiple regression analysis as
      a simultaneous function of annual average temperature and relative humidity,
      matched the observed values. We infer that parallel changes in melanization and
      desiccation resistance may result from decreasing annual average temperature and
      relative humidity along increasing latitude as well as altitude on the Indian
      subcontinent.

PMID- 20050770
TI  - Egg formation in lepidoptera.
AB  - Reproductive biology in the Twentieth Century produced comprehensive descriptions
      of the mechanisms of egg formation in most of the major orders of insects. While
      many general principles of ovarian development and physiology emerged, every
      order turned out to have a set of its own special motifs. Discovery of the
      lepidopteran motifs is summarized in this essay. The emphasis is on developmental
      mechanisms, beginning with the early growth and differentiation of female germ
      cells and ending, after many turns in morphogenesis, physiology and biosynthesis,
      with eggs that are filled with yolk and encased in chorions. Examples of uniquely
      lepidopteran traits include the cellular composition of ovarian follicles, the
      number of tubular ovarioles in which they mature, the functions of cell-to-cell
      junctional complexes in their maturation, their use of glycosaminoglycans to
      maintain intercellular patency during vitellogenesis, the role of proton and
      calcium pumps in their ion physiology, a separate postvitellogenic period of
      water and inorganic ion uptake, and the fine structure and protein composition of
      their chorions. Discovery of this combination of idiosyncracies was based on
      advances in the general concepts and techniques of cell and molecular biology and
      on insights borrowed from studies on other insects. The lepidopteran ovary in
      turn has contributed much to the understanding of egg formation in insects
      generally.

PMID- 20050771
TI  - Demography and life history of the egg parasitoid, Trichogramma brassicae, on two
      moths Anagasta kuehniella and Plodia interpunctella in the laboratory.
AB  - The egg parasitoid, Trichogramma brassicae Bezdenko (Hymenoptera:
      Trichogrammatidae) is the most important and widely distributed species of
      Trichogramma in Iran. It attacks eggs of several lepidopterous pests, and is a
      major biological control agent. Rearing parasitoids is necessary for experimental
      work, and, potentially, for mass release in the field. Selecting a suitable host
      is critical for developing a successful rearing method. If other conditions are
      the same, the rate of population increase will be a suitable indicator of
      parasitoid performance on different hosts. However, conclusions based on a single
      generation can be misleading because of the learning ability of parasitoids. Life
      history parameters of T. brassicae were studied on two hosts easily reared in the
      laboratory, Anagasta kuehniella Zeller, and Plodia interpunctella Hubner
      (Lepidoptera: Pyralidae). All the experiments were carried out at 24 +/- 1
      degrees C, 65+/-10% RH, and 16:8 L:D photoperiod. Eight parameters including
      gross and net reproductive rates (GRR and R(0) respectively), intrinsic rate of
      natural increase (r(m)), finite rate of population increase (lambda), intrinsic
      birth and death rates (b and d respectively), cohort generation time (T), and
      doubling time (DT) were compared between two hosts for two generations. All
      parameters showed a highly significant difference (alpha = 0.01) between hosts.
      GRR, R(0), r(m), lambda, and b were higher, while d, T, and DT were lower in
      Anagasta than Plodia. The intrinsic rate of natural increase was 0.2912 and
      0.2145 female/female/day and net replacement rate was 45.51 and 19.26
      female/female/generation in Anagasta and Plodia respectively. Differences between
      generations were significant except for r(m), lambda, and d. The net replacement
      rate was 28.56 and 39 in the 1(st) and 2(nd) generations respectively. These
      results showed that A. kuehniella was a better host than P. interpunctella.
      Higher reproduction occurred in the second generation that may be due to
      increased adaptation to experimental conditions.

PMID- 20050772
TI  - Response of the cutworm Spodoptera litura to sesame leaves or crude extracts in
      diet.
AB  - The effects of extracts of sesame, Sesamum indicum L. (Liamiales: Pedaliaceae),
      and whole leaves of some selected cultivars of sesame were tested using a natural
      host Spodoptera litura (F.) (Lepidoptera: Noctuidae). Indices taken using the
      immature stages include; diet utilization, growth and development and induction
      of detoxification enzymes. The results indicate that S. litura generally selects
      its food amongst cultivars within 6 hours after food presentation. Growth and
      development of the insect is controlled also by plant acceptability and quality.
      Although all the cultivars tested significantly limit insect growth and
      development the variety 56S-radiatum did not allow a complete life cycle as
      pupation from first instar stage was 0%. Generally the crucial period for
      immature S. litura was the larval period, especially the first two instars where
      the weight of an insect fed on an experimental diet was three times lower than
      that of a control diet. The larval developmental period was greater than 40 days
      as compared to 17 days for insects fed a control diet. S. litura also had lowered
      efficiency in utilizing ingested food, from a low of 13% in a sesame cultivar to
      45% in the control diet. The key detoxification enzyme was a glutathione s
      transferase that was confirmed by a 6-fold increase between S. litura fed a plant
      cultivar vs. a control diet towards the substrate 1,2-dichloro-4-nitrobenzene.
      First and second instars of S. litura have a relatively reduced detoxification of
      enzymes in response to plant cultivar diets leading to low survival. A 3% v/w
      crude extract of the cultivars increased enzyme induction towards all the tested
      substrates.

PMID- 20050773
TI  - Pathogenicity of the Fungus, Aspergillus clavatus, isolated from the locust,
      Oedaleus senegalensis, against larvae of the mosquitoes Aedes aegypti, Anopheles
      gambiae and Culex quinquefasciatus.
AB  - The use of insect pathogenic fungi is a promising alternative to chemical control
      against mosquitoes. Among the Hyphomycetes isolated from insects for mosquito
      control, the genus Aspergillus remains the least studied. In September 2005, four
      fungi were isolated from the Senegalese locust, Oedaleus senegalensis Kraus
      (Orthoptera: Acrididae), collected in Dakar, Senegal. One of these fungi,
      identified as Aspergillus clavatus, Desmazieres (Eurotiales: Trichocomaceae) was
      highly pathogenic against larvae of the mosquitoes Aedes aegypti L., Anopheles
      gambiae s.l. Giles and Culex quinquefasciatus Say (Diptera: Culicidae). An
      application of 1.2 mg/ml dry conidia yielded 100% mortality after 24 hours
      against both Ae. aegypti and Cx. quinquefasciatus while with An. gambiae it was
      95%. With unidentified species in the genus Aspergillus, mortality after 24 h was
      <5% against all the larval species. Application of A. clavatus produced in a
      wheat powder medium using doses ranging between 4.3 to 21x107 spores/ml, caused
      11 to 68% mortality against Cx. quinquefasciatus at 24h, and 37 to 100% against
      Ae. aegypti. Microscopic observations showed fungal germination on both Ae.
      aegypti and Cx. quinquefasciatus larvae. Histological studies revealed that A.
      clavatus penetrated the cuticle, invaded the gut and disintegrated its cells.
      Some Cx. quinquefasciatus larvae, treated with A. clavatus reached the pupal
      stage and produced infected adults. However, the infection was mainly located on
      the extremity of their abdomen. These results suggest that A. clavatus could be
      an effective tool to manage mosquito proliferation.

PMID- 20050774
TI  - Daily activity patterns of two co-occurring tropical satyrine butterflies.
AB  - Adult males and females of many insect species are expected to adjust their daily
      activity pattern in order to avoid stressful climatic conditions and increase the
      chances to encounter sexual partners. Using scan sampling methods associated with
      focal individual observations it was found that two satyrine butterflies of
      similar size and morphology, Hermeuptychia hermes (Fabricius) (Leptidoptera:
      Nymphalidae) and Paryphthimoides phronius (Godart), show completely different
      daily activity patterns on forest edges in southeastern Brazil. Hermeuptychia
      hermes presents one abundance peak in the morning and another in the late
      afternoon, while P. phronius abundance peaks in the mid-day, remaining stable
      until 1700 h. This difference is probably due to the occurrence of territorial
      behavior in the later species. The beginning of territorial defense by P.
      phronius males coincided with the time of new-born female activity. However,
      newly hatched females were not sexually receptive. The afternoon territoriality
      in male P. phronius may be in part related to mate acquisition. However, why the
      abundance of H. hermes decreases when the abundance of P. phronius increases is
      less clear.

PMID- 20050775
TI  - Population dynamics of the rubber plantation litter beetle Luprops tristis, in
      relation to annual cycle of foliage phenology of its host, the para rubber tree,
      Hevea brasiliensis.
AB  - The population dynamics of the rubber plantation litter beetle, Luprops tristis
      Fabricius 1801 (Coleoptera: Tenebrionidae) was assessed in relation to the
      phenology of leaf shedding and defoliation pattern of para rubber trees, Hevea
      brasiliensis Mull. Arg (Malpighiales: Euphorbiaceae), during a two year study
      period. The abundance of adults, larvae and pupae per 1m(2) of litter sample was
      recorded. Post dormancy beetles appeared in leaf litter following annual leaf
      shedding, whereas larvae, pupae and teneral adults were present after leaf flush.
      No stages were recorded from plantations following the summer rains until the
      annual litter fall in the next season. Parental adults peaked at the time of leaf
      sprouting and tender leaf fall. Larvae and teneral adults peaked at the time of
      premature fall of green leaves and flowers. Teneral adults of six age classes
      were recorded and all entered dormancy irrespective of the feeding time available
      to each age class. Females outnumbered males in the parent generation, while the
      sex ratio of new generation adults was not biased towards either sex. The
      phenological stages of rubber trees included leaf fall in late December and early
      January, leaf sprouting and new leaf production in January and flowering in
      February. All feeding stages of L. tristis peaked in abundance when premature
      leaves are most abundant in the leaf litter. Prediction of the timing of
      appearance of various developmental stages of L. tristis in plantations, invasion
      into buildings and intensity of population build up in rubber belts is possible
      by tracking the phenology of leaf fall in rubber plantations, time of return of
      post dormancy adults and the onset of summer rainfall. Perfect synchrony was
      recorded between the field return of parental adults with annual leaf shedding,
      the oviposition phase of parental adults with tender leaf fall at the time of
      leaf sprouting, and larval and teneral adult stages with premature fall of
      leaves. Premature leaf availability is suggested as contributing to the
      reproductive efficiency of parental adults, the survival of early developmental
      stages and of new generation adults during dormancy.

PMID- 20050776
TI  - Physiological activity of neuropeptide f on the hindgut of the blood-feeding
      hemipteran, Rhodnius prolixus.
AB  - Current hypotheses propose that, in the invertebrates, neuropeptide F (NPF), the
      vertebrate NPY homologue, may be capable of regulating responses to diverse cues
      related to nutritional status and feeding. An investigation into the effects of
      Drosophila melanogaster NPF (DrmNPF) and Anopheles gambiae NPF (AngNPF) on
      hindgut physiology of Rhodnius prolixus Stal (Heimptera: Reduviidae) suggests a
      myoinhibitory role for these peptides and the R. prolixus native peptide.
      Extracts of the central nervous system of R. prolixus were processed and several
      HPLC-fractions revealed NPF-like activity within the nanomolar equivalent range
      when tested using the hindgut contraction assay. Although NPF has been shown to
      decrease epithelial membrane potential in Aedes aegypti larval midgut
      preparations, NPF does not appear to play a role in epithelial transport of
      potassium in the hindgut. While the function of NPF has yet to be established,
      NPF-like effects suggest multiple physiological roles for NPF among
      invertebrates.

PMID- 20050777
TI  - Preliminary results on evaluation of chickpea, Cicer arietinum, genotypes for
      resistance to the pulse beetle, Callosobruchus maculatus.
AB  - Abstract The chickpea, Cicer arietinum L. (Fabales: Fabaceae), seeds are
      vulnerable, both in the field and in storage, to attack by seed-beetles. Beetles
      of the genus Callosobruchus are major storage pests of chickpea crops and cause
      considerable economic losses. In the present study, a total of 11 chickpea
      genotypes including five 'kabuli' (Mexican white, Diyar, CA 2969, ILC 8617 and
      ACC 245) and six 'desi' chickpeas (ICC 1069, ICC 12422, ICC 14336, ICC 4957, ICC
      4969 and ICC 7509) were evaluated for resistance to the pulse beetle
      Callosobruchus maculatus F. (Coleoptera: Bruchidae). Resistance was evaluated by
      measuring percent damage to seeds. Damage to seeds by C. maculatus was manifested
      by the round exit holes with the 'flap' of seed coat made by emerging adults. Of
      the 11 genotypes tested, only one (ICC 4969) exhibited a complete resistance to
      C. maculatus in both free-choice and no-choice tests; no seed damage was found
      over the test period. In general, the 'desi' chickpeas were more resistant to C.
      maculatus than the 'kabuli' chickpeas. Among the tested chickpea genotypes, only
      ICC 4969 can be used as a source of C. maculatus resistance in breeding
      programmes that could then be grown in organic cultivation free from pesticides.

PMID- 20050778
TI  - Soybean flour and wheat germ proportions in artificial diet and their effect on
      the growth rates of the tobacco budworm, Heliothis virescens.
AB  - Soybean flour and wheat germ are the two most important protein components of
      wheat germ-based insect artificial diets. The effect of modifying the proportion
      of these two ingredients in a Noctuidae-specific diet was investigated utilizing
      the tobacco budworm Heliothis virescens (F.) (Lepidoptera: Noctuidae), with the
      goal of developing a suboptimal diet that, without drastically affecting this
      insect's growth and reproductive rates, could manifest subtle negative effects in
      this insect. The original diet formula contained 2.51% protein. When the
      proportions of soybean flour and wheat germ were changed to 2.15% protein the net
      reproductive rate of the first generation was significantly lower. In the second
      generation, the net reproductive rate, development time, percent female
      survivorship, fertility, intrinsic rate of increase, finite rate of increase and
      female longevity were significantly lower in both the 2.15% and 2.26% protein
      diets. The survival rate of immatures to the adult stage was 1% in the 2.05%
      protein diet in the first generation. Interestingly, females exposed to these
      suboptimal diets produced a significantly higher number of eggs but the survival
      of their larvae was significantly reduced. It is evident from these results that
      modifications to the protein content and the nutrient composition profile of the
      original wheat germ-based insect artificial formula can be used to produce subtle
      negative effects on the growth of tobacco budworm.

PMID- 20050779
TI  - Distributional patterns of Pseudacteon associated with the Solenopsis saevissima
      complex in South America.
AB  - Classical biological control efforts against imported fire ants have largely
      involved the use of Pseudacteon parasitoids. To facilitate further exploration
      for species and population biotypes a database of collection records for
      Pseudacteon species was organized, including those from the literature and other
      sources. These data were then used to map the geographical ranges of species
      associated with the imported fire ants in their native range in South America. In
      addition, we found geographical range metrics for all species in the genus and
      related these metrics to latitude and host use. Approximately equal numbers of
      Pseudacteon species were found in temperate and tropical regions, though the
      majority of taxa found only in temperate areas were found in the Northern
      Hemisphere. No significant differences in sizes of geographical ranges were found
      between Pseudacteon associated with the different host complexes of fire ants
      despite the much larger and systemic collection effort associated with the S.
      saevissima host group. The geographical range of the flies was loosely associated
      with both the number of hosts and the geographical range of their hosts.
      Pseudacteon with the most extensive ranges had either multiple hosts or hosts
      with broad distributions. Mean species richnesses of Pseudacteon in locality
      species assemblages associated with S. saevissima complex ants was 2.8 species,
      but intensively sampled locations were usually much higher. Possible factors are
      discussed related to variation in the size of geographical range, and areas in
      southern South America are outlined that are likely to have been under-explored
      for Pseudacteon associated with imported fire ants.

PMID- 20050781
TI  - Spitting performance parameters and their biomechanical implications in the
      spitting spider, Scytodes thoracica.
AB  - Spitting spiders Scytodes spp. subdue prey by entangling them at a distance with
      a mixture of silk, glue, and venom. Using high-speed videography and differential
      interference contrast microscopy, the performance parameters involved in spit
      ejection by Scytodes thoracica (Araneae, Scytodidae) were measured. These will
      ultimately need to be explained in biomechanical and fluid dynamic terms. It was
      found that the ejection of "spit" from the opening of the venom duct (near the
      proximal end of the fang) was orderly. It resulted in a pattern that scanned
      along a lateral-medial axis (due to fang oscillations) while traversing from
      ventral to dorsal (due to cheliceral elevation). Each lateral-to-medial sweep of
      a fang produced silk-borne beads of glue that were not present during each
      subsequent medial-to-lateral sweep. The ejection of "spit" was very rapid. A full
      scan (5-57 fang cycles, one upsweep of a chelicera) typically occupied less than
      30 ms and involved fang oscillations at 278-1781 Hz. Ejection velocities were
      measured as high as 28.8 m/s. The "spit" was contractile. During the 0.2 s
      following ejection, silk shortened by 40-60% and the product of a full scan by
      both of the chelicerae could exert an aggregate contractile force of 0.1 - 0.3
      mN. Based on these parameters, hypotheses are described concerning the
      biomechanical and fluid dynamic processes that could enable this kind of material
      ejection.

PMID- 20050782
TI  - Comparison of similarity coefficients used for cluster analysis with amplified
      fragment length polymorphism markers in the silkworm, Bombyx mori.
AB  - Establishing accurate genetic similarity and dissimilarity between individuals is
      an essential and decisive point for clustering and analyzing inter and intra
      population diversity because different similarity and dissimilarity indices may
      yield contradictory outcomes. We assessed the variations caused by three commonly
      used similarity coefficients including Jaccard, Sorensen-Dice and Simple matching
      in the clustering and ordination of seven Iranian native silkworm, Bombyx mori L.
      (Lepidoptera: Bombycidae), strains analyzed by amplified fragment length
      polymorphism markers. Comparisons among the similarity coefficients were made
      using the Spearman correlation analysis, dendrogram evaluation (visual inspection
      and consensus fork index--CI(C)), projection efficiency in a two-dimensional
      space, and groups formed by the Tocher optimization procedure. The results
      demonstrated that for almost all methodologies, the Jaccard and Sorensen-Dice
      coefficients revealed extremely close results, because both of them exclude
      negative co-occurrences. Due to the fact that there is no guarantee that the DNA
      regions with negative cooccurrences between two strains are indeed identical, the
      use of coefficients such as Jaccard and Sorensen-Dice that do not include
      negative co-occurrences was imperative for closely related organisms.

PMID- 20050783
TI  - Food preferences of the rubber plantation litter beetle, Luprops tristis, a
      nuisance pest in rubber tree plantations.
AB  - Massive invasion of the litter dwelling beetle, Luprops tristis Fabricius
      (Coleoptera: Tenebrionidae), numbering about 0.5 to 4 million per residential
      building following summer showers, and their prolonged stay in a state of
      dormancy, make them an extreme nuisance in rubber tree plantation belts of the
      Western Ghats in south India. Food preference of post-dormancy adults, larvae and
      teneral adults stages towards tender, mature and senescent leaves were assessed
      in three choice and no choice leaf disc tests. All stages have strong preference
      towards fallen tender leaves and lowest preference towards senescent leaves
      indicating that leaf age is a major attribute determining food selection and food
      preference of L. tristis. Ready availability of the preferred, prematurely
      fallen, tender rubber tree leaves as a food resource is suggested as being
      responsible for the exceptionally high abundance of L. tristis in rubber tree
      plantation belts.

PMID- 20050784
TI  - Pulmonary dendritic cells in lungs of preterm infants: neglected participants in
      bronchopulmonary dysplasia?
AB  - Preterm infants are at risk for bronchopulmonary dysplasia (BPD), a chronic lung
      disease characterized by disrupted alveolar remodeling and microvascular
      dysangiogenesis. The pathogenesis of BPD is multifactorial, with contributions
      from antenatal and/or postnatal infection and inflammation. The potential role of
      dendritic cells, critical immune regulatory cells with potent angiogenic
      activities, remains undetermined. We studied the prevalence and topography of
      dendritic cells in postmortem lungs of short- and long-term ventilated preterm
      infants born between 23 and 29 weeks in gestation. Controls were age-matched
      infants who had lived less than 12 hours. Dendritic cells were identified by anti
      DC-SIGN immunohistochemistry and were co-localized with endothelial and smooth
      muscle cells by double immunofluorescence. Lungs of early and late control
      infants without evidence of antenatal infection contained scattered DC-SIGN
      positive dendritic cells in the peripheral lung parenchyma. Lungs of early
      control infants with a history of chorioamnionitis/antenatal infection and lungs
      of short- or long-term ventilated preterm infants showed a dramatic (more than 3
      fold) increase in dendritic cells. Double labeling highlighted a close
      association between dendritic cells and small- or medium-sized pulmonary vessels.
      In conclusion, we demonstrated that dendritic cells are an integral component of
      normal postcanalicular lung development. Antenatal infection and ventilation/BPD
      are associated with significant pulmonary recruitment of dendritic cells. The
      recently described angiogenic effects of dendritic cells and their intimate
      association with the pulmonary microvasculature indicate that dendritic cells may
      participate in BPD-associated dysangiogenesis. Elucidation of the role of this
      immunovascular axis may lead to novel therapeutic approaches to BPD.

PMID- 20050788
TI  - The vast majority of scientific journals have an impact factor of less than 1.

PMID- 20050785
TI  - Comparison of holding strength of suture anchors on human renal capsule.
AB  - INTRODUCTION: The use of surgical clips as suture anchors has made laparoscopic
      partial nephrectomy (LPN) technically simpler by eliminating the need for
      intracorporeal knot tying. However, the holding strength of these clips has not
      been analyzed in the human kidney. Therefore, the safety of utilizing suture
      anchors is unknown as the potential for clip slippage or renal capsular tears
      during LPN could result in postoperative complications including hemorrhage and
      urinoma formation. With the above in mind, we sought to compare the ability of
      Lapra-Ty clips and Hem-o-lok clips to function as suture anchors on human renal
      capsule. METHODS: Fresh human cadaveric kidneys with intact renal capsules were
      obtained. A Lapra-Ty clip (Ethicon, Cincinnati, OH) or a Hem-o-lok clip (Weck,
      Raleigh, NC) was secured to a no. 1 Vicryl suture (Ethicon) with and without a
      knot, as is typically utilized during the performance of LPN. The suture was then
      placed through the renal capsule and parenchyma and attached to an Imada
      Mechanical Force Tester (Imada, Northbrook, IL). The amount of force required
      both to violate the renal capsule and to dislodge the clip was recorded
      separately. RESULTS: Six Lapra-Ty clips and six Hem-o-lok clips were tested. The
      mean force in newtons required to violate the renal capsule for the Lapra-Ty
      group was 7.33 N and for the Hem-o-lok group was 22.08 N (p < 0.001). The mean
      force required to dislodge the clip from the suture for the Lapra-Ty group was
      9.0 N and for the Hem-o-lok group was 3.4 N (p < 0.001). When two Hem-o-lok clips
      were placed on the suture in series, the mean force required to dislodge the
      clips was 10.6 N. CONCLUSION: When compared with Lapra-Ty clips, using two Hem-o
      lok clips may provide a more secure and cost-effective method to anchor sutures
      on human renal capsule when performing LPN.

PMID- 20050789
TI  - Financial outcomes of palliative care services in an intensive care unit.

PMID- 20050790
TI  - Tumor board response.

PMID- 20050791
TI  - Overpowering or understanding?

PMID- 20050792
TI  - Treatment preferences: impact of risk and benefit in decision-making.
AB  - Understanding treatment preferences of seriously ill patients is complex.
      Previous studies have shown a correlation between the burden and outcome of a
      treatment and the likelihood a patient will accept a given intervention. In this
      study the Willingness to Accept Life Sustaining Treatment (WALT) survey was used
      in a predominantly Latino population receiving care at a large urban safety net
      hospital. Eligible patients were cared for by one of four clinics: (1) human
      immunodeficiency virus (HIV); (2) geriatrics; (3) oncology; or (4) cardiology.
      Hypothetical scenarios reflecting outcomes of resuscitation were presented and
      patients were given information on the burden and outcome of treatment. They were
      then given the option of accepting or declining treatment; 237 completed the
      survey. Patients in our study were willing to accept a high level of cognitive
      (vegetative state) and functional (bed-bound) impairment even when the chance of
      recovery was exceedingly low.

PMID- 20050793
TI  - Hypercalcemia of malignancy #151.

PMID- 20050794
TI  - Oral oxymorphone #181.

PMID- 20050796
TI  - Computed tomography-guided coblation and cementoplasty of a painful acetabular
      metastasis: an effective palliative treatment.
AB  - Percutaneous cementoplasty is an effective palliative treatment for acetabular
      metastases. Potential problems with this technique include inadequate filling and
      intra-articular cement leakage, leading to increased hip pain. We present a case
      of metastatic non-small cell lung cancer in which we illustrate how using
      radiofrequency coblation prior to cement injection creates a well-defined cavity
      allowing controlled cement injection limiting cement extrusion. To the best of
      our knowledge this is the first report in which coblation of an acetabular
      metastasis prior to cement filling has been performed.

PMID- 20050802
TI  - The cancer pain management plan.

PMID- 20050804
TI  - Evolution of senescence in nature: physiological evolution in populations of
      garter snake with divergent life histories.
AB  - Evolutionary theories of aging are linked to life-history theory in that age
      specific schedules of reproduction and survival determine the trajectory of age
      specific mutation/selection balances across the life span and thus the rate of
      senescence. This is predicted to manifest at the organismal level in the
      evolution of energy allocation strategies of investing in somatic maintenance and
      robust stress responses in less hazardous environments in exchange for energy
      spent on growth and reproduction. Here we report experiments from long-studied
      populations of western terrestrial garter snakes (Thamnophis elegans) that reside
      in low and high extrinsic mortality environments, with evolved long and short
      life spans, respectively. Laboratory common-environment colonies of these two
      ecotypes were tested for a suite of physiological traits after control and
      stressed gestations. In offspring derived from control and corticosterone-treated
      dams, we measured resting metabolism; mitochondrial oxygen consumption, ATP and
      free radical production rates; and erythrocyte DNA damage and repair ability. We
      evaluated whether these aging biomarkers mirrored the evolution of life span and
      whether they were sensitive to stress. Neonates from the long-lived ecotype (1)
      were smaller, (2) consumed equal amounts of oxygen when corrected for body mass,
      (3) had DNA that damaged more readily but repaired more efficiently, and (4) had
      more efficient mitochondria and more efficient cellular antioxidant defenses than
      short-lived snakes. Many ecotype differences were enhanced in offspring derived
      from stress-treated dams, which supports the conclusion that nongenetic maternal
      effects may further impact the cellular stress defenses of offspring. Our
      findings reveal that physiological evolution underpins reptilian life histories
      and sheds light on the connectedness between stress response and aging pathways
      in wild-dwelling organisms.

PMID- 20050805
TI  - My, how time flies: Foodborne Pathogens and Disease to begin its seventh year
      with publication frequency to increase in 2010.

PMID- 20050806
TI  - Erythrocyte invasion and merozoite ligand gene expression in severe and mild
      Plasmodium falciparum malaria.
AB  - Erythrocyte invasion is central to malaria parasite replication and virulence.
      Plasmodium falciparum parasites use different alternative erythrocyte receptors
      and vary in expression of erythrocyte-binding antigenic (EBA) proteins and
      reticulocyte-binding protein homologues (Rh). Parasite invasion phenotypes and
      schizont-stage transcript expression profiles of the 8 eba and Rh protein-coding
      genes without internal stop codons were determined for 163 clinical isolates
      cultured ex vivo in The Gambia. There was extensive diversity in ability to
      invade erythrocytes treated with neuraminidase, trypsin, or chymotrypsin, and
      severe malaria isolates were less restricted by trypsin treatment than were mild
      malaria isolates (P = .015). Expression profiles of the eba and Rh genes showed
      distinct clusters indicating coordinated alternative transcription. The most
      divergent of 5 major clusters was dominated by Rh2b, with virtually no expression
      of eba175 or eba140 genes (which were dominant in the other 4 clusters).
      Particular transcripts were significantly correlated with parasitemia (Rh5 was
      positively correlated and eba140 negatively correlated; P < .01 for both) and age
      of patients (eba181 was positively correlated and eba175 negatively correlated; P
      < .001 for both) but not with invasion phenotypes or severity of malaria. Severe
      and mild malaria isolates were also evenly represented across the different
      expression clusters.

PMID- 20050807
TI  - Microcapsules embedded with three-dimensional fibrous scaffolds for cell culture
      and tissue engineering.
AB  - Aggregating into multicellular spheroids within alginate-poly-L-lysine-alginate
      (APA) microcapsules is important in maintaining the cellular viability and
      specific functions. However, in the absence of a vascular network, cells in the
      core of large-sized spheroids are gradually necrotic because of oxygen transfer
      limitations. In this study, a novel APA microcapsule embedded with three
      dimensional fibrous scaffolds (called APA-FS) was proposed to eliminate cellular
      necrosis by regulating cells to form multi-small spheroids. HepG2 cells were
      embedded within the APA-FS to form spheroids and the state of these spheroids was
      evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide assay,
      glucose/lactate metabolism, live/dead staining, and hematoxylin and eosin
      staining. Comparing with the conventional APA microcapsules, the cells within APA
      FS organized into multi-small spheroids. The size of these spheroids depended on
      the concentration of fibrous scaffolds embedded within the microcapsules. In the
      APA-FS embedded with 5% (v/v) fibrous scaffolds, the average size of cellular
      spheroids was controlled below 100 microm and the cellular viability was
      increased by 50% than the control. The results of live/dead staining and
      hematoxylin and eosin staining showed that the improved cellular viability might
      be attributed to the decreased necrosis in the core of these spheroids. The
      improved viability of cells demonstrated the efficiency of this technology. These
      findings implied that this system might provide a more suitable culture
      environment for a variety of tissue engineering applications.

PMID- 20050808
TI  - Multiscale topological guidance for cell alignment via direct laser writing on
      biodegradable polymer.
AB  - Direct laser writing on biodegradable polymer to create microchannels for
      aligning cells is presented here. This technique offers the advantages of ease-of
      manufacturing, ease-of-design, high-speed single-step fabrication, and
      noncontacting to the material. In this work, microchannels of 100 microm width,
      100 microm depth, and 50 microm intervals were created on a biodegradable polymer
      film directly using a Ti-sapphire femtosecond pulsed laser. Multiscale
      topological features were achieved as a result of the laser beam-material
      interaction. These topological features were used to guide cell alignment in the
      microchannels. We present results on the morphology of poly(L-lactide-co-epsilon
      caprolactone) copolymer micromachined by femtosecond laser and demonstrate the
      attachment and alignment of C2C12 myoblast cells in the microchannels. C2C12
      cells exhibited favorable attachment in the channels after 1 day of seeding. High
      degree of alignment was observed after 4 days as cells proliferated into a
      confluent patch inside the channels. This work demonstrated the potential of wavy
      surface features combined with appropriate channel size for high-density cell
      alignment using direct laser writing. This method also offers the opportunity to
      incorporate multiscale topological guidance on other biodegradable polymer
      implants, such as vascular scaffolds and stents, which require directed cell
      organization.

PMID- 20050809
TI  - Mesenchymal stem cells and bovine bone mineral in sinus lift procedures--an
      experimental study in sheep.
AB  - INTRODUCTION: New reconstructive and less invasive methods have been searched to
      optimize bone formation and osseointegration of dental implants in maxillary
      sinus augmentation. PURPOSE: The aim of the presented ovine split-mouth study was
      to compare bovine bone mineral (BBM) alone and in combination with mesenchymal
      stem cells (MSCs) regarding their potential in sinus augmentation. MATERIAL AND
      METHODS: Bilateral sinus floor augmentations were performed in six adult sheep.
      BBM and MSCs were placed into the test side and only BBM in the contra-lateral
      control side of each sheep. Animals were sacrificed after 8 and 16 weeks.
      Augmentation sites were analyzed by computed tomography, histology, and
      histomorphometry. RESULTS: The initial volumes of both sides were similar and did
      not change significantly with time. A tight connection between the particles of
      BBM and the new bone was observed histologically. Bone formation was
      significantly (p = 0.027) faster by 49% in the test sides. CONCLUSION: The
      combination of BBM and MSCs accelerated new bone formation in this model of
      maxillary sinus augmentation. This could allow early placement of implants.

PMID- 20050810
TI  - Expression of Reg family proteins in embryonic stem cells and its modulation by
      Wnt/beta-catenin signaling.
AB  - Regenerating islet (Reg) proteins are involved in the proliferation and
      differentiation of diverse cell types. However, whether embryonic stem cells
      (ESCs) express Reg genes and their corresponding proteins remains unknown. In
      this study, we probed the expression of Reg family members by mouse ESCs (mESCs).
      Mouse Reg1 and Reg3gamma were detected in undifferentiated stem cells.
      Furthermore, we tested if gastrin--an inducer of Reg1 expression in committed
      cells--up-regulates the Reg1 gene in mESCs. Gastrin did not affect the expression
      of Reg1 either in self-renewing mESCs or under conditions permitting their
      differentiation. Moreover, overexpression of Reg genes found in various forms of
      cancer has been linked to dysregulated activation of the canonical Wnt/beta
      catenin cascade. Given the important roles of Wnt signaling in stem cells, we
      investigated if activation of Wnt alters the expression of Reg genes in mESCs.
      Wnt activation led to an increase in Reg1 gene expression with a concomitant
      increase in the amount of secreted Reg1 protein. Finally, the expression pattern
      of genes indicative of differentiation was examined in mESCs that were either
      exposed to soluble Reg1 or overexpressed the Reg1 gene. This is the first account
      of expression of Reg family members by ESCs. Our results show that the canonical
      Wnt cascade affects Reg expression and warrants further studies into the
      potential roles of Reg proteins in stem cell physiology.

PMID- 20050811
TI  - Proteomic characterization of mesenchymal stem cell-like populations derived from
      ovine periodontal ligament, dental pulp, and bone marrow: analysis of
      differentially expressed proteins.
AB  - Postnatal mesenchymal stem/stromal-like cells (MSCs) including periodontal
      ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and bone marrow
      stromal cells (BMSCs) are capable of self-renewal and differentiation into
      multiple mesenchymal cell lineages. Despite their similar expression of MSC
      associated and osteoblastic markers, MSCs retain the capacity to generate
      structures resembling the microenvironments from which they are derived in vivo
      and represent a promising therapy for the regeneration of complex tissues in the
      clinical setting. With this in mind, systematic approaches are required to
      identify the differential protein expression patterns responsible for lineage
      commitment and mediating the formation of these complex structures. This is the
      first study to compare the differential proteomic expression profiles of ex vivo
      expanded ovine PDLSCs, DPSCs, and BMSCs derived from an individual donor. The two
      dimensional electrophoresis was performed and regulated proteins were identified
      by liquid chromatography--electrospray-ionization tandem mass spectrometry (MS
      and MS/MS), database searching, and de novo sequencing. In total, 58 proteins
      were differentially expressed between at least 2 MSC populations in both sheep,
      12 of which were up-regulated in one MSC population relative to the other two. In
      addition, the regulation of selected proteins was also conserved between
      equivalent human MSC populations. We anticipate that differential protein
      expression profiling will provide a basis for elucidating the protein expression
      patterns and molecular cues that are crucial in specifying the characteristic
      growth and developmental capacity of dental and non-dental tissue-derived MSC
      populations. These expression patterns can serve as important tools for the
      regeneration of particular tissues in future stem cell-based tissue engineering
      studies using animal models.

PMID- 20050812
TI  - Targeting the angiopoietin (Ang)/Tie-2 pathway in the crosstalk between acute
      myeloid leukaemia and endothelial cells: studies of Tie-2 blocking antibodies,
      exogenous Ang-2 and inhibition of constitutive agonistic Ang-1 release.
AB  - BACKGROUND: The Tie-2 receptor can bind its agonistic ligand Angiopoietin-1 (Ang
      1) and the potential antagonist Ang-2. Tie-2 can be expressed both by primary
      human acute myeloid leukaemia (AML) cells and endothelial cells, and Tie-2
      blocking antibodies are now being evaluated in clinical trials for cancer
      treatment. DESIGN AND METHODS: We investigated the effects of Tie-2-blocking
      antibodies, exogenous Ang-2 and pharmacological agents on AML cell proliferation
      and the release of angioregulatory mediators. RESULTS: Tie-2-blocking antibodies
      had a growth inhibitory effect on human AML cells co-cultured with microvascular
      endothelial cells, but this inhibition was not observed when leukaemic cells were
      co-cultured with fibroblasts or osteoblasts. AML cell viability in co-cultures
      was not altered by anti-Tie-2. Furthermore, anti-Tie-2 decreased hepatocyte
      growth factor (HGF) levels and increased CXCL8 levels in co-cultures, whereas the
      levels of endocan (a proteoglycan released by endothelial cells) were not
      altered. The only significant effects of exogenous Ang-2 were decreased levels of
      HGF and endocan. Constitutive AML cell release of agonistic Ang-1 was decreased
      by the proteasomal inhibitor bortezomib and the specific IkappaB-kinase/NFkappaB
      inhibitor BMS-345541. CONCLUSION: We conclude that various strategies for
      inhibition of Tie-2-mediated signalling should be considered in AML therapy,
      possibly in combination with other antiangiogenic strategies.

PMID- 20050813
TI  - NX-1207: a novel investigational drug for the treatment of benign prostatic
      hyperplasia.
AB  - IMPORTANCE OF THE FIELD: Lower urinary tract symptoms (LUTS) associated with
      benign prostatic hyperplasia (BPH) is a common affliction among older men that
      can have significant impact on health-related quality of life. BPH is a
      progressive condition that can lead to complications including acute urinary
      retention (AUR) and to surgical intervention. There is an ongoing need for new,
      safe and effective treatments for BPH. Currently available therapies have
      significant safety and efficacy limitations. NX-1207 is a promising first-in
      class drug currently in Phase III trials for the treatment of BPH. AREAS COVERED
      IN THIS REVIEW: This review provides an overview of BPH and currently approved
      medical treatments and drugs as described in the literature and treatment
      practice guidelines in the past 10 years, an outline of the results of the Phase
      II trials of NX-1207 and an expert opinion on the role NX-1207 may play in the
      treatment of men with clinical BPH. WHAT THE READER WILL GAIN: This review aims
      to introduce readers to NX-1207, a new treatment for BPH that is administered in
      an office-based procedure by transrectal intraprostatic injection under
      ultrasound guidance. NX-1207 has selective pro-apoptotic properties, which
      induces focal cell loss in prostate leading to prostate volume reduction with
      both short- and long-term symptomatic improvement. TAKE HOME MESSAGE: In four US
      clinical trials to date, NX-1207 has shown evidence of symptomatic improvement
      substantially better than currently approved BPH medications with no significant
      safety issues. Larger Phase III trials are ongoing to further confirm the
      efficacy, safety and tolerability for this minimally invasive, anesthetic free,
      clinic-based treatment for BPH.

PMID- 20050814
TI  - Cost effectiveness of varenicline versus bupropion and unaided cessation for
      smoking cessation in a cohort of Finnish adult smokers.
AB  - OBJECTIVE: To assess the cost effectiveness of varenicline compared with
      bupropion or unaided cessation for smoking cessation in Finnish adult smokers.
      RESEARCH DESIGN AND METHODS: The BENESCO (BENEfits of Smoking Cessation on
      Outcomes) Markov model was used to follow a hypothetical cohort of smokers making
      a single quit attempt over a lifetime. Gender and age-specific data on the
      incidence and prevalence of five smoking-related diseases (chronic obstructive
      pulmonary disease [COPD], lung cancer, coronary heart disease [CHD], stroke and
      asthma exacerbations) were included in the model. Life-years (LYs), quality
      adjusted life-years (QALYs), total treatment costs and the lifetime cumulative
      incidence of these parameters were the primary outcomes evaluated, and they were
      compared for varenicline versus bupropion and varenicline versus unaided
      cessation. The primary data were derived from Finnish publications and databases.
      Deterministic and probabilistic sensitivity analyses were performed to test the
      robustness of the base-case model. RESULTS: The treatment cohort comprised 229
      301 smokers making a quit attempt. In the lifetime simulation, use of varenicline
      prevented 1965 and 5057 additional cases of smoking-related disease, and 1184 and
      3047 deaths attributable to smoking, when compared with bupropion and unaided
      cessation, respectively. Compared with bupropion and unaided cessation
      varenicline treatment yielded 4392 and 11 303 additional LYs (4851 and 12 485
      QALYs), respectively. Varenicline resulted in cost savings of 15 million and 43
      million euros (euro) compared with bupropion and unaided cessation, respectively.
      In the 20-year time horizon analysis, varenicline yielded an incremental cost
      effectiveness ratio (ICER) of euro8791/QALY and euro7791/QALY gained in
      comparison to bupropion and unaided cessation, respectively. Sensitivity analyses
      supported the robustness of the base-case results for varenicline. CONCLUSION:
      Varenicline dominated over its comparators, i.e. it was more effective and
      resulted in cost saving compared with bupropion and unaided cessation.

PMID- 20050815
TI  - Evaluation of 3-5 months' add-on therapy with montelukast in patients with non
      controlled asthma in Austria: the STAR open-label, real-world, observational
      study.
AB  - OBJECTIVE: To assess the current state of asthma management in Austria and
      evaluate improvement of symptoms and quality of life (QoL) in asthma patients by
      adding the controller substance montelukast to existing therapy. RESEARCH DESIGN
      AND METHODS: Office-based pneumologists across Austria were invited to
      participate in an open-label, multicenter observational study. Male and female
      patients aged from 12-50 years with mild or moderate persistent asthma according
      to GINA guidelines and FEV(1) > 70% predicted were included if they were on
      concurrent asthma treatment, but still had persistent symptoms and reduced
      quality of life. Asthma control was assessed at time of patient anamnesis and
      subsequent follow-up visits. In addition, a physical examination was performed,
      lung function (FEV(1)) was measured and two types of validated QoL questionnaires
      were used: the Juniper Asthma Control Questionnaire was evaluated and documented
      by the physicians at each study visit and the Asthma Quality of Life
      Questionnaire was completed by the patients following each visit. RESULTS: A
      total of 851 patients (343 males, 508 females) were included and 328 patients
      were eligible for evaluation 3-5 months after completing at least two study
      visits. QoL rating by patients was available for 263 at baseline and for 216
      patients after 3-5 months. The physicians' rating of asthma-related QoL showed
      improvements between 6.66 and 11.80% in the categories: nocturnal awakening,
      morning asthma symptoms, reduction of daily activities, wheezing and dyspnoea,
      but no reduction in the use of short acting ss(2)-agonists (SABA). The QoL judged
      by the patients by means of the QoL-Q showed statistically significant
      improvements in 13 of 15 parameters of QoL. The categories: response to cigarette
      smoke and response to air pollution showed positive trends (not significant)
      while the improvement of shortness of breath, response to dust, frustration,
      cough, anxiety, chest pressure, sleep quality, worries about asthma, wheezing,
      symptoms at heavy and moderate exercise and impairment of daily activities and
      activities at work reached statistical significance. CONCLUSION: This open-label,
      multicenter observational study shows significant improvement in six QoL
      parameters evaluated by the physicians and in 13 out of 15 QoL categories judged
      by the patients 3-5 months after adding montelukast to the ongoing asthma
      treatment in patients with mild or moderate persistent asthma. Limitations to
      these conclusions are the lack of a placebo control group (as this was an open
      label study) and the continuing basal asthma therapy, which might contribute to
      improvement of asthma control.

PMID- 20050816
TI  - A survey of scale insects (Sternorryncha: Coccoidea) occurring on table grapes in
      South Africa.
AB  - Increasing international trade and tourism have led to an increase in the
      introduction of exotic pests that pose a considerable economic threat to the agro
      ecosystems of importing countries. Scale insects (Sternorryncha: Coccoidea) may
      be contaminants of export consignments from the South African deciduous fruit
      industry to the European Union, Israel, United Kingdom and the United States, for
      example. Infestations of immature scale insects found on South African fruit
      destined for export have resulted in increasing rates of rejection of such
      consignments. To identify the risk posed by scale insect species listed as
      phytosanitary pests on table grapes to the abovementioned importing countries, a
      field survey was undertaken in 2004-2005 in vineyards throughout all grape
      producing regions in South Africa. Coccoidea species found during the current
      field survey were Planococcus ficus (Signoret), Pseudococcus longispinus
      (Targioni Tozzetti), Coccus hesperidum L. and Nipaecoccus viridis (Newstead).
      With the exception of Pl. ficus, which has only been collected from Vitis
      vinifera (Vitaceae) and Ficus carica (Moraceae) in South Africa, these species
      are polyphagous and have a wide host range. None of the scale insect species
      found to occur in vineyards in South Africa pose a phytosanitary risk to
      countries where fruit are exported except for Ferrisia malvastra (McDaniel) and
      N. viridis that have not been recorded in the USA. All scale insects previously
      found in vineyards in South Africa are listed and their phytosanitary status
      discussed. The results of the survey show that the risk of exporting scale insect
      pests of phytosanitary importance on table grapes from South Africa is limited.

PMID- 20050817
TI  - VPAC receptor mediated tumor cell targeting by protamine based nanoparticles.
AB  - The receptors for vasoactive intestinal peptide (VIP), VPAC1-, VPAC2-, and PAC1
      receptor are overexpressed by various tumor cells. VIP can target these receptors
      and transport conjugates into the cell. However, the use of VIP for tumor cell
      targeting is hampered by the peptides short half-lives due to enzymatic
      degradation. Because protamine-based nanoparticles (proticles) protect the
      peptide and serve as peptide depot, we explored the potential of proticles as
      carrier for VIP-conjugated molecules. The VIP-loaded proticles were stable as
      shown by Fluorescence Correlation Spectroscopy. With Confocal Laser Scanning
      Microscopy, we observed VIP-loaded proticles to specifically target the tumor
      cells. The cell binding triggered the substance release and conjugate
      internalization of VIP-Cy3 in vitro and ex vivo by human tumors. We observed VIP
      releasing proticle depots distributed in rat tissue and human tumors. Our
      findings warrant further studies to explore the proticles potential to enable
      peptide-mediated targeting for in vivo and clinical applications.

PMID- 20050818
TI  - Toxic effects of D-galactose on thymus and spleen that resemble aging.
AB  - Continuous low-dose injection of d-galactose induces changes in mice that
      resemble accelerated aging. As such, these mice have been used as models to study
      mechanisms of aging. Here, we examined whether repeated (daily, for 60 days)
      subcutaneous injections (at 50 mg D-galactose/kg) into young adult (i.e., 2-month
      old) mice induced changes in key immune system organs that were on par with those
      associated with aging. The results showed that galactose-treated mice develop
      histologic changes in their thymic cortical and medullary regions;
      immunohistochemical analysis revealed unorganized distributions of keratin-5 and
      keratin-8 proteins in the thymus of these hosts. These histological changes in
      the thymus of D-galactose-treated mice were also observed in the organs of aged
      (i.e., 24-month-old control mice); however, in this latter group, these changes
      were accompanied by a strong infiltration of adipose cells. Galactose-treated
      mice also evinced alterations within their splenic white and red pulp. Further,
      ultrastructural analyses of the thymus and spleen of the treated mice revealed
      increases in irregularly shaped lymphocytes bearing visible pyknosis. It was also
      seen that levels of autophagy within thymic epithelial cells were greatly
      decreased in the tissues of the galactose-treated mice, an outcome also seen in
      aged mice. Lastly, the level of memory T-lymphocytes and percentage of IgM-B220-B
      lymphocytes in spleens of the galactose-treated mice were both increased (albeit
      insignificantly so) relative to values among splenocytes of age-matched control;
      however, these levels were not clearly as elevated as would be expected in
      "elderly" mice. Taken together, our results strongly suggest that d-galactose
      treatment can induce structural changes in the thymus and spleen, and some
      changes in organ-associated cell phenotypes, that are similar to several effects
      seen with aging. However, the fact that many endpoints do not appear to be truly
      reflective of what should be seen in immune system organs/cells of "elderly" mice
      now calls into question the appropriateness of the use of d-galactose (i.e., is
      it histologically/immunotoxicologically-proper?) to create age-mimicry in mice.

PMID- 20050819
TI  - Nipple discharge screening.
AB  - Nipple discharge is a common complaint among women. It is classified as normal or
      abnormal depending on features such as laterality, cycle variation, quantity,
      color or presentation (i.e., induced vs spontaneous). It can be related to benign
      conditions, such as intraductal papilloma, duct ectasia, plasma cell mastitis or
      galactorrhea; or to malignant conditions such as ductal, lobular or papillary
      carcinoma. Techniques used in nipple discharge evaluation include mammography,
      ultrasound, cytology (which could be assisted by a mammary pump), duct endoscopy,
      ductography, immunochemical methods and at least surgical excision of the
      pathological ducts for diagnosis and treatment in the same procedure.

PMID- 20050821
TI  - Plasma level of malondialdehyde in the cases of acute paraquat intoxication.
AB  - BACKGROUND, MATERIAL, AND METHODS: To assess plasma malondialdehyde (MDA) level
      as a clinical marker in acute paraquat (PQ) intoxication, we sequentially
      investigated 74 patients (40 males and 34 females, aged 49.9 +/- 16.2 years), all
      of whom ingested PQ as a means of suicide from July to December 2008. RESULTS:
      The baseline level of MDA (10.8 +/- 3.5 microM) had no correlation with plasma PQ
      levels of 22.1 +/- 48.7 microg/mL (median: 1.9, range <0.01-228.5) or with volume
      of PQ ingested. However, the following parameters were significantly different
      between survivors and nonsurvivors: the amount of PQ ingestion, plasma PQ levels,
      basal MDA levels, WBC, hemoglobin, hematocrit, platelet counts, albumin, BUN,
      creatinine, potassium, amylase, and arterial blood gas analysis (pH, pCO(2), HCO(
      )(3)).The nonsurvivors' baseline MDA (11.4 +/- 3.8 vs. 9.8 +/- 2.8, p = 0.040)
      was higher than the survivors. However, the baseline level was not a predictor of
      mortality in the univariate and the multivariate binary logistic analyses. Among
      the patients whose MDA levels were measured sequentially, 58.3% of the patients
      (35 out of 60) showed fluctuating MDA levels, 25% (n = 15) showed steady
      decreases, with only 16.6% (n = 10) showing steady increases in MDA levels during
      the observation period. These findings imply the presence of active MDA
      metabolism and/or that the half-life of MDA is very short in the human body.
      CONCLUSION: Both cross-sectional and sequential measurements of plasma MDA do not
      provide reliable information on outcome in patients with acute PQ intoxication.

PMID- 20050820
TI  - Physical activity and lung cancer among non-smokers: a pilot molecular
      epidemiological study within EPIC.
AB  - The association between physical activity, potential intermediate biomarkers and
      lung cancer risk was investigated in a study of 230 cases and 648 controls nested
      within the European Prospective Investigation of Cancer and Nutrition. Data on
      white blood cell aromatic-DNA adducts by (32)P-post-labelling and glutathione
      (GSH) in red blood cells were available from a subset of cases and controls.
      Compared with the first quartile, the fourth quartile of recreational physical
      activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95%
      confidence interval (CI) 0.35-0.90), higher GSH levels (+1.87 micromol GSH g(-1)
      haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR
      1.05, 95% CI 0.38-2.86). Despite being associated with recreational physical
      activity, in these small-scale pilot analyses GSH levels were not associated with
      lung cancer risk (OR 0.95, 95% CI 0.84-1.07 per unit increase in GSH levels).
      Household and occupational activity was not associated with lung cancer risk or
      biomarker levels.

PMID- 20050822
TI  - Pirfenidone: an anti-fibrotic therapy for progressive kidney disease.
AB  - IMPORTANCE OF THE FIELD: Many chronic diseases of various etiologies lead to
      fibrosis and organ dysfunction. Despite many advances in medicine in recent
      years, options to slow the progression of fibrotic diseases have remained
      limited. The recent availability of pirfenidone, an antifibrotic and anti
      inflammatory investigational agent, thus offers a new hope for treating
      progressive fibrotic diseases. AREAS COVERED IN THIS REVIEW: This review provides
      concise review of the available data regarding the mechanism and pharmacokinetics
      of pirfenidone and preclinical and clinical data regarding efficacy and safety in
      fibrotic diseases of the kidney. It also reviews results of clinical trials
      involving pirfenidone in other fibrotic diseases. WHAT THE READER WILL GAIN: The
      review will provide in-depth review of pirfenidone with a renal focus. TAKE HOME
      MESSAGE: Because many of the available clinical trials have been small and/or
      uncontrolled, conclusive evidence regarding efficacy and safety of pirfenidone is
      lacking, particularly in patients with renal or hepatic dysfunction. Larger
      studies are needed to better understand long-term efficacy and safety of this
      medication in various patient populations.

PMID- 20050823
TI  - Clinically validated approaches to the treatment of autoimmune diseases.
AB  - IMPORTANCE OF THE FIELD: Autoimmune diseases are pathological conditions in which
      "self-tolerance" has been broken, and an immune response has been mounted against
      the body's own tissues. More than seventy autoimmune diseases have been
      described, some of which are systemic and others of which are organ-specific.
      Although many of these diseases are rare, the collective prevalence of autoimmune
      diseases in the United States alone is between 5 and 8%, and is increasing. AREAS
      COVERED IN THIS REVIEW: Herein, we review the exciting advances made during the
      past decade (1999 - 2009) in the development of clinically-validated agents for
      the treatment of autoimmune disease. We focus on five of the most prevalent
      conditions: rheumatoid arthritis, psoriasis, multiple sclerosis, Crohn's disease,
      and systemic lupus erythematosus. The discussion is largely restricted to agents 
      both small molecules and macromolecules - that have advanced through randomized,
      controlled clinical trials. WHAT THE READER WILL GAIN: An overview of the
      pathogenesis of each disease is provided, along with a description of the
      therapies. Results from pivotal clinical trials are tabulated for four of the
      disease areas. We also provide summaries of experiences with both failed clinical
      trials and side effects observed during the course of clinical investigations. We
      conclude the review with thoughts on current challenges in the field and the
      prospect for future innovations. TAKE HOME MESSAGE: During the past decade, some
      of the largest advances in the treatment of autoimmune disease have arisen from
      highly potent and selective macromolecule-based therapies (e.g. antibodies,
      recombinant proteins and fusion proteins). Together, these clinical experiences
      have provided insight into the critical mechanisms in autoimmune pathogenesis,
      including inflammatory cytokine release, T-cell migration and co-stimulation, and
      B-cell function.

PMID- 20050824
TI  - The development of the tumor vascular-disrupting agent ASA404 (vadimezan, DMXAA):
      current status and future opportunities.
AB  - IMPORTANCE OF THE FIELD: Targeting tumor vasculature with antiangiogenic agents
      improves outcomes achieved with chemotherapy in some cancers, but toxicity limits
      their applicability. Tumor vascular-disrupting agents (tumor-VDAs) induce an
      acute collapse in tumor vascular supply; ASA404 (vadimezan, 5,6
      dimethylxanthenone-4-acetic acid [DMXAA]) is the tumor-VDA most advanced in
      clinical development. Recent randomized trials of ASA404 in combination with
      chemotherapy suggested a survival advantage in NSCLC comparable to that achieved
      with bevacizumab, but with little additional toxicity. Phase III trials in
      advanced NSCLC have completed accrual, and a review of this exciting agent is
      timely. AREAS COVERED IN THIS REVIEW: This review focuses on the development of
      ASA404 to date, its mechanisms of action, the current body of clinical research
      and potential avenues for therapeutic use. It includes all completed clinical
      trials since it entered clinical testing in 1995 through to 2009. WHAT THE READER
      WILL GAIN: This review will help the reader to understand why ASA404 is unique
      among tumor-VDAs; the clinical trial methodology required to evaluate such
      agents; and its remarkable potential clinical utility. TAKE HOME MESSAGE: ASA404
      is a tumor-VDA that offers considerable potential to improve outcomes in cancer
      patients in combination with existing treatments.

PMID- 20050825
TI  - Tagatose: from a sweetener to a new diabetic medication?
AB  - IMPORTANCE OF THE FIELD: Tagatose is a naturally occurring simple sugar that is a
      more palatable bulk low-calorie (1.5 kcal/g) sweetener. It was approved as a food
      additive by the FDA in 2003. Tagatose has been studied as a potential
      antidiabetic and antiobesity medication. In preliminary studies in humans,
      tagatose has shown a low postprandial blood glucose and insulin response. Its
      proposed mechanism of action may involve interference in the absorption of
      carbohydrates by inhibiting intestinal disaccharidases and glucose transport. It
      may also act through hepatic inhibition of glycogenolysis. AREAS COVERED IN THIS
      REVIEW: This article summarizes tagatose Phase I and II diabetes trials. It
      describes the pharmacodynamics and possible mechanism of action of this agent.
      Literature from 1974 to 2009 is reviewed. WHAT THE READER WILL GAIN: Better
      understanding of the implications of postprandial hyperglycemia. An appreciation
      of the liver as a target of glucose control. Increased awareness of tagatose, a
      sweetener, as a potential new medication that operates through improvement of
      postprandial hyperglycemia. TAKE HOME MESSAGE: Tagatose is currently being
      studied as a postprandial antihyperglycemic agent that may be safer with regard
      to hypoglycemia. Ongoing Phase III clinical trials will provide more definitive
      answers.

PMID- 20050827
TI  - Expression and localization of cystic fibrosis  transmembrane conductance
      regulator in human gingiva.
AB  - CFTR (cystic fibrosis transmembrane conductance regulator) is a cAMP-activated
      chloride channel that regulates electrolyte and water transport. The present
      study investigated the expression and localization of CFTR in human gingiva and
      explored the possible association of CFTR with periodontal conditions. CFTR
      expression in gingival biopsies from five periodontally healthy subjects and ten
      subjects with chronic periodontitis and in the RHGE (reconstituted human gingival
      epithelia) was detected by immunohistochemistry, whereas its expression in
      gingival biopsies was analysed by immunofluorescence staining. CFTR mRNA was
      analysed by reverse transcription-PCR. CFTR mRNA was detected in human gingival
      epithelia and RHGE. CFTR protein was detected in gingival biopsies from both
      healthy subjects and individuals with periodontitis and in RHGE. In healthy
      subjects, CFTR expression was mainly confined to the granular and spinous layers
      of epithelia and localized on the cell membrane. In patients with periodontitis,
      CFTR was detected in all layers of epithelia and the underlying connective
      tissues. The mean CFTR expression levels in periodontitis patients were
      significantly higher than those in healthy subjects. The present study for the
      first time showed the expression and localization of CFTR in human gingival
      epithelia. Elevated CFTR expression in periodontitis subjects implies the
      possible involvement of CFTR in periodontal disease pathogenesis. Further study
      is warranted to confirm the present findings.

PMID- 20050826
TI  - Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of
      epoxyeicosatrienoic acids degradation attenuates hypertension and hypertension
      induced end-organ damage in Ren-2 transgenic rats.
AB  - Recent studies have shown that the renal CYP450 (cytochrome P450) metabolites of
      AA (arachidonic acid), the vasoconstrictor 20-HETE (20-hydroxyeicosatetraenoic
      acid) and the vasodilator EETs (epoxyeicosatrienoic acids), play an important
      role in the pathophysiology of AngII (angiotensin II)-dependent forms of
      hypertension and the associated target organ damage. The present studies were
      performed in Ren-2 renin transgenic rats (TGR) to evaluate the effects of chronic
      selective inhibition of 20-HETE formation or elevation of the level of EETs,
      alone or in combination, on the course of hypertension and hypertension
      associated end-organ damage. Both young (30 days of age) prehypertensive TGR and
      adult (190 days of age) TGR with established hypertension were examined.
      Normotensive HanSD (Hannover Sprague-Dawley) rats served as controls. The rats
      were treated with N-methylsulfonyl-12,12-dibromododec-11-enamide to inhibit 20
      HETE formation and/or with N-cyclohexyl-N-dodecyl urea to inhibit soluble epoxide
      hydrolase and prevent degradation of EETs. Inhibition in TGR of 20-HETE formation
      combined with enhanced bioavailability of EETs attenuated the development of
      hypertension, cardiac hypertrophy, proteinuria, glomerular hypertrophy and
      sclerosis as well as renal tubulointerstitial injury. This was also associated
      with attenuation of the responsiveness of the systemic and renal vascular beds to
      AngII without modifying their responses to noradrenaline (norepinephrine). Our
      findings suggest that altered production and/or action of 20-HETE and EETs plays
      a permissive role in the development of hypertension and hypertension-associated
      end-organ damage in this model of AngII-dependent hypertension. This information
      provides a basis for a search for new therapeutic approaches for the treatment of
      hypertension.

PMID- 20050828
TI  - Management of congenital cytomegalovirus infection: an evidence-based approach.
AB  - Abstract Despite cytomegalovirus being the most common congenital infection
      leading to psychomotor impairment and sensori-neural hearing loss, little is
      known about early identification and management of congenitally infected
      neonates. This article reviews the literature and devises an algorithm for
      identification and management of these neonates. CONCLUSION: Application of the
      current knowledge in the management of congenital cytomegalovirus infected
      neonates could be beneficial, until further evidence is available.

PMID- 20050829
TI  - Do centimetres matter? Self-reported versus estimated height measurements in
      parents.
AB  - AIM: An impressive discrepancy between reported and measured parental height is
      often observed. The aims of this study were: (a) to assess whether there is a
      significant difference between the reported and measured parental height; (b) to
      focus on the reported and, thereafter, measured height of the partner; (c) to
      analyse its impact on the calculated target height range. METHODS/RESULTS: A
      total of 1542 individual parents were enrolled. The parents were subdivided into
      three groups: normal height (3-97th Centile), short (<3%) and tall (>97%)
      stature. Overall, compared with men, women were far better in estimating their
      own height (p < 0.001). Where both partners were of normal, short or tall
      stature, the estimated heights of their partner were quite accurate. Women of
      normal stature underestimated the short partner and overestimated the tall
      partner, whereas male partners of normal stature overestimated both their short
      as well as tall partners. Women of tall stature estimated the heights of their
      short partners correctly, whereas heights of normal statured men were
      underestimated. On the other hand, tall men overestimated the heights of their
      female partners who are of normal and short stature. Furthermore, women of short
      stature estimated the partners of normal stature adequately, and the heights of
      their tall partners were overestimated. Interestingly, the short men
      significantly underestimated the normal, but overestimated tall female partners.
      CONCLUSION: Only measured heights should be used to perform accurate evaluations
      of height, particularly when diagnostic tests or treatment interventions are
      contemplated. For clinical trails, we suggest that only quality measured parental
      heights are acceptable, as the errors incurred in estimates may enhance/conceal
      true treatment effects.

PMID- 20050830
TI  - The prognostic value of early aEEG in asphyxiated infants undergoing systemic
      hypothermia treatment.
AB  - BACKGROUND: Induced moderate hypothermia (HT) for 72 h has been shown to reduce
      the combined outcome of death or severe neurodevelopmental disabilities in
      asphyxiated full-term infants. A pathological amplitude integrated EEG background
      as early as 3-6 h after birth, has been shown to correlate to poor prognosis.
      AIM: The aim of this study was to investigate the correlation between amplitude
      integrated EEG during HT treatment and short-term outcome in asphyxiated full
      term infants with moderate/severe hypoxic-ischaemic encephalopathy. METHODS:
      Between December 2006 and December 2007, 24 infants were treated with moderate HT
      (33.5 degrees C for 72 h) using a cooling mattress. Motor functions were assessed
      at 4 and 12 months of age. RESULTS: Of the total birth cohort of 28,837 infants,
      26 infants fulfilled the criteria for HT treatment (0.9/1000) of whom 23 was
      treated with HT and all of these infants had available amplitude integrated EEG
      data. Normal 1-year outcome was found in 10/15 infants with severely abnormal
      burst-suppression pattern or worse at 6 h of age. Severe abnormalities were found
      to be significantly predictive for abnormal outcome after 36 h. CONCLUSION: Among
      asphyxiated infants treated with HT, only those who had aEEG abnormalities
      persisting at and beyond 24 h after birth showed poor neurological outcome at 1
      year.

PMID- 20050831
TI  - Development of adaptive motor behaviour in typically developing infants.
AB  - AIM: During motor development, infants learn to select adaptive motor strategies
      out of their motor repertoire. The aim of this study is twofold: first, to
      investigate whether the presence of adaptive motor behaviour can be observed
      reliably, and second, to explore the ages at which clinically observable
      transition to adaptive motility emerges for four specific motor functions:
      abdominal progression, sitting motility, reaching and grasping. METHODS: The
      reliability part of the study included 38 assessments of term and preterm infants
      in the age range of 4-18 months. The longitudinal prospective study included 30
      term born typically developing infants with nine assessments between 3 and 18
      months. On the basis of standardized video-recordings of spontaneous motor
      behaviour, the presence of adaptive motor strategies was scored. RESULTS: Intra-
      and interobserver reliability were good. Clinically observable transitions to
      adaptive selection started to emerge from 6 months onwards and peaked between 8
      and 15 months. Transitions developed gradually and occurred at specific ages for
      different motor functions. CONCLUSION: Transition to adaptive motor behaviour can
      be observed reliably. Adaptive motor behaviour develops gradually from 6 months
      onwards at function-specific ages. Comparison of our results to literature showed
      that changes measured by neurophysiologic methods precede clinically observed
      transitions.

PMID- 20050832
TI  - HMG CoA reductase inhibition and endothelial function in children with chronic
      kidney disease (CKD)--a pilot study.

PMID- 20050834
TI  - The risk of overuse injuries.

PMID- 20050836
TI  - Prediction and causal inference.

PMID- 20050837
TI  - Cross-talk between macro- and microcirculation.
AB  - Physiologically, macro- and microcirculation differ markedly as macrocirculation
      deals with pulsatile pressure and flow and microcirculation with steady pressure
      and flow. Various such haemodynamic aspects correspond to a large heterogeneity
      in the structure and function of the vascular tree. In the past, diseases such as
      hypertension and diabetes mellitus were classified on the basis of the structure
      and function of small and large arteries. The purpose of this paper is to review
      the cross-talk between the micro- and macrocirculation. We shall discuss this
      cross-talk from the perspective of the development, physiology and pathology of
      the entire arterial tree.

PMID- 20050838
TI  - Pharmacodynamic effects of haematopoietic cytokines: the view of a clinical
      oncologist.
AB  - The production of haematopoietic cells is under the tight control of a group of
      haematopoietic cytokines. Each cytokine has multiple actions mediated by
      receptors whose cytoplasmic domains contain specialized regions initiating
      survival, proliferation, differentiation commitment, maturation and functional
      activation. Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO),
      and thrombopoiesis-stimulating agents are in routine clinical use to stimulate
      cell production and in total have been used in the management of many millions of
      patients. G-CSF regulates neutrophil production to maintain blood neutrophil
      counts in the normal range. G-CSF is used to prevent febrile neutropenia or to
      increase dose-density in chemotherapy regimens. Despite consistently showing a
      shorter duration of neutropenia, multiple prospective randomized trials have
      documented only modest clinical benefit. A clinical advantage of dose-dense
      chemotherapy has been shown only in specific chemotherapy regimens. Professional
      recommendations tailor the use of CSFs to patients with a high risk of adverse
      outcome of febrile neutropenia. EPO was used to prevent anaemia requiring red
      blood cell transfusion. However, recent studies strongly suggest a negative
      overall effect on mortality, without a plausible biological explanation. It is
      now proposed that its use should be restricted to patients in clinical trials.
      Thrombopoiesis-stimulating agents have only been recently introduced into the
      market for splenectomized and non-splenectomized patients with immune
      thrombocytopenic purpura, a rare disease. Before widely used in other conditions
      such as chemotherapy-induced thrombocytopenia, the lessons learned from the
      example of G-CSF and EPO should be taken seriously.

PMID- 20050839
TI  - An integrated model for the glucose-insulin system.
AB  - The integrated glucose-insulin model was originally developed on a variety of
      intravenous glucose provocation experiments in healthy volunteers and type 2
      diabetic patients. The model, which simultaneously describes time-courses of
      glucose and insulin based on mechanism-based components for production,
      elimination and homeostatic feedback, has been further extended to oral glucose
      provocations, meal tests and insulin administration. The model has been used to
      describe experiments ranging from 4 to 24 hr. Applications of the integrated
      glucose-insulin model include the clinical assessment of the mechanism of action
      of anti-diabetic drugs and the magnitude of their effects. Finally, the model was
      used for optimizing the design of provocation experiments.

PMID- 20050840
TI  - Safety of administration of human butyrylcholinesterase and its conjugates with
      soman or VX in rats.
AB  - We evaluated the effects of conjugated enzyme-nerve agent product resulting from
      the inhibition of bioscavenger human serum butyrylcholinesterase (Hu BChE) by
      nerve agents soman or VX. Rats were trained on a multiple Fixed-Ratio 32,
      Extinction 30 sec. (FR32, Ext30) schedule of food reinforcement and then injected
      (i.m.) with Hu BChE (30 mg/kg), equivalent amounts of Hu BChE-soman conjugate
      (GDC), Hu BChE-VX conjugate, oxotremorine (OXO) (0.316 mg/kg) or vehicle (n = 8,
      each group). On the day of injection and on 10 subsequent daily sessions,
      performance was evaluated on the FR32, Ext30 schedule. Neither conjugates nor Hu
      BChE produced a performance deficit under the schedule. OXO produced a
      substantial decrease in responding on the day of administration, with complete
      recovery observed on subsequent sessions. None of the treatments affected
      circulating acetylcholinesterase (AChE) activity when evaluated 24-72 hr after
      injection. The dose of Hu BChE produced a 20,000-fold increase above baseline in
      circulating BChE activity. Pathological evaluation of organ systems approximately
      2 weeks following administration of conjugates or Hu BChE alone did not show
      toxicity. Taken together, these results suggest that Hu BChE - nerve agent
      conjugates produced following bioscavenger protection against nerve agents soman
      and VX do not appear to be particularly toxic. These results add to the safety
      assessment of Hu BChE as a bioscavenger countermeasure against nerve agent
      exposure.

PMID- 20050841
TI  - Model-based neutrophil-guided dose adaptation in chemotherapy: evaluation of
      predicted outcome with different types and amounts of information.
AB  - One of the most employed approaches to reduce severe neutropenia following
      anticancer drug regimens is to reduce the consecutive dose in fixed steps,
      commonly by 25%. Another approach has been to use pharmacokinetic (PK) sampling
      to tailor dosing, but only rarely have model-based computer approaches utilizing
      collected PK and/or pharmacodynamic (PD) data been used. A semi-mechanistic model
      for myelosuppression that can characterize the interindividual and interoccasion
      variability in the time-course of neutrophils following administration of a wide
      range of anticancer drugs may be used in a clinical setting for model-based dose
      individualization. The aim of this study was to compare current stepwise
      procedures to model-based dose adaptation by simulations, and investigate if the
      overall dose intensity in the population could be increased without increasing
      the risk of severe toxicity. The value of various amounts of PK- and/or PD
      information was compared to standard dosing strategies using a maximum a
      posteriori procedure in NONMEM. The results showed that when information on
      neutrophil counts was available, the additional improvement from PK sampling was
      negligible. Using neutrophil sampling at baseline and an observation near the
      predicted nadir increased the number of patients in the target range by 27% in
      comparison with a one-sided 25% dose adjustment schedule, while keeping the
      number of patients experiencing severe toxicity at a comparable low level after
      five courses of treatment. High interindividual variability did not limit the
      benefit of model-based dose adaptation, whereas high interoccasion variability
      was predicted to make any dose adaptation method less successful. This study
      indicates that for successful model-based dose adaptation clinically, there is no
      need for drug concentration sampling, and that one extra neutrophil measurement
      in addition to the pre-treatment value is sufficient to limit severe neutropenia
      while increasing dose intensity.

PMID- 20050842
TI  - Environmental exposure to methylmercury is associated with a decrease in nitric
      oxide production.
AB  - Some studies have recently suggested that mercury (Hg)-exposed populations face
      increased risks of cardiovascular diseases, and experimental data indicate that
      such risks might be due to reductions in nitric oxide bioavailability. However,
      no previous study has examined whether Hg exposure affects plasma nitrite
      concentrations in humans as an indication of nitric oxide production. Here, we
      investigated whether there is an association between circulating nitrite and Hg
      concentrations in whole blood, plasma and hair from an exposed methylmercury
      (MeHg) population. Hair and blood samples were collected from 238 persons exposed
      to MeHg from fish consumption. Hg concentrations in plasma (PHg), whole blood
      (BHg) and hair Hg (HHg) were determined by inductively coupled plasma-mass
      spectrometry. Mean BHg content was 49.8 +/- 35.2 microg/l, mean PHg was 7.8 +/-
      6.9 microg/l and HHg 14.6 +/- 10.6 microg/g. Mean plasma nitrite concentration
      was 253.2 +/- 105.5 nM. No association was found between plasma nitrite
      concentration and BHg or HHg concentrations in a univariate model. However,
      multiple regression models adjusted for gender, age and fish consumption showed a
      significant association between plasma nitrite and plasma Hg concentration (beta
      = -0.1, p < 0.001). Our findings constitute preliminary clinical evidence that
      exposure to MeHg may cause inhibitory effects on the production of endothelial
      nitric oxide.

PMID- 20050843
TI  - Active-site concentrations of chemicals - are they a better predictor of effect
      than plasma/organ/tissue concentrations?
AB  - Active-site concentrations can be defined as the concentrations of unbound,
      pharmacologically active substances at the site of action. In contrast, the total
      concentrations of the drug in plasma/organ/tissue also include the protein- or
      tissue-bound molecules that are pharmacologically inactive. Plasma and whole
      tissue concentrations are used as predictors of effects and side effects because
      of their ease of sampling, while the concentrations of unbound drug in tissue are
      more difficult to measure. However, with the introduction of microdialysis and
      subsequently developed techniques, it has become possible to test the free drug
      hypothesis. The brain is an interesting organ in this regard because of the
      presence of the blood-brain barrier with its tight junctions and active efflux
      and influx transporters. We have proposed that research into brain drug delivery
      be divided into three main areas: the rate of delivery (PS, CL(in)), the extent
      of delivery (K(p,uu)) and the non-specific affinity of the drug to brain tissue,
      described by the volume of distribution of unbound drug in the brain
      (V(u,brain)). In this way, the concentration of unbound drug at the target site
      can be estimated from the total brain concentration and the plasma concentration
      after measuring the fraction of unbound drug. Results so far fully support the
      theory that active site concentrations are the best predictors when active
      transport is present. However, there is an urgent need to collect more relevant
      data for predicting active site concentrations in tissues with active
      transporters in their plasma membranes.

PMID- 20050844
TI  - Sex differences in animal models of depression and antidepressant response.
AB  - Many stress-related mental disorders, including depression and post-traumatic
      stress disorder occur more often in women than in men. While social and cultural
      factors certainly contribute to these differences, neurobiological sex
      differences seem to also play an important role. A rapidly burgeoning literature
      from basic and clinical research documents sex differences in brain anatomy,
      chemistry and function, as well as in stress and drug responses. For example,
      some clinical studies have reported that women may have a better outcome when
      treated with selective serotonin re-uptake inhibitors, in comparison to tricyclic
      antidepressants. Furthermore, relatively limited basic research has been devoted
      to developing animal models and consequently describing drug treatments which are
      sensitive to sex differences. In this MiniReview, we discuss sex differences in
      behavioural aspects, as well as neurochemical, neurobiological and
      pharmacological findings that we have collected from several different animal
      models and tests of depression. These are the forced swim test, the chronic mild
      stress and the learned helplessness models, the Flinders sensitive line rats,
      which is a genetic model of depression and the lipopolysaccharide-induced
      sickness behaviour, a putative inflammatory model of depression. Collectively,
      our data have shown that in all animal models assayed, serotonergic neurochemical
      responses were differently affected in males and females, ultimately producing
      sex-dependent behavioural effects. In addition, Flinders sensitive line rats
      exhibited a sexually dimorphic response to chronic antidepressant treatment.
      These sex-differentiated neurochemical and behavioural alterations lend support
      to a major role of serotonin in the mediation of sexually dimorphic responses.

PMID- 20050845
TI  - Amelioration of oxaliplatin neurotoxicity by drugs in humans and experimental
      animals: a minireview of recent literature.
AB  - The broad spectrum anti-neoplastic drug oxaliplatin is a third-generation
      platinum compound that inhibits DNA synthesis, mainly by causing intrastrandal
      cross-links in DNA. The drug is particularly useful alone and in combination with
      fluoruracil and leucovorin in colorectal cancer, but it is also used for other
      cancers such as those of the ovary, lung, breast and liver, as well as non
      Hodgkin's lymphoma. The drug is known to cause neurological, gastrointestinal and
      haematological toxicities. Neurotoxicity occurs in most of the treated patients
      and is considered to be a serious limitation for the use of the drug. The
      mechanism of the neurotoxicity is not known with certainty but may involve
      prolongation of sodium channels opening. Strategies to ameliorate oxaliplatin
      neurotoxicity include the use of several 'neuroprotective' drugs. This MiniReview
      attempts to list and comment on the action and use of some of these agents, which
      include carbamazepine, gabapentin, calcium and magnesium salts, reduced
      glutathione, N-acetylcysteine and a few others. None of these drugs have been
      proven to be effective in large, controlled, clinical trials.

PMID- 20050846
TI  - Electrophysiological characterization of isolated human atrial myocytes exposed
      to tegaserod.
AB  - Tegaserod (Teg), a 5-hydroxytryptamine type-4 (5-HT(4)) receptor partial agonist,
      represents a novel treatment for irritable bowel syndrome with constipation and
      chronic constipation. Cardiovascular safety data from pooled clinical studies
      showed a signal suggestive of increased occurrence of ischaemic cardiovascular
      events in patients exposed to Teg versus placebo. Thereafter, marketing of Teg
      was suspended in the USA and other countries. The clinical data did not
      demonstrate a causative effect but raised questions of whether a non-recognized
      effect on the heart was present. Our aim was to evaluate for arrhythmogenic
      potential of Teg on human cardiomyocytes. Cells isolated from human atrial
      specimens during cardiac surgery were used to assess the effects of Teg (1, 10,
      30 and 100 nM) on action potential and I(f) (funny current) by patch-clamp
      technique. Results showed that Teg (at all concentrations tested) did not
      significantly affect action potential characteristics of atrial myocytes when
      driven at different rates (0.2, 0.5 and 1 Hz). In contrast, 5HT significantly
      prolonged action potential duration (1 and 10 nM) and caused cell un-excitability
      (100 nM). Teg, at the highest concentration tested (100 nM, corresponding to 10
      times C(max), produced by the recommended dose of 6 mg b.i.d.) increased the I(f)
      amplitude and caused a shift of its activation curve. This effect of a high
      concentration of Teg is not considered clinically relevant. When evaluated on
      single human atrial cells, Teg does not appear to exhibit arrhythmogenic
      properties, as it did not affect the action potential profile.

PMID- 20050847
TI  - On setting the first dose in man: quantitating biotherapeutic drug-target binding
      through pharmacokinetic and pharmacodynamic models.
AB  - Although the three (perhaps four) phases of clinical drug development are well
      known, it is relatively unappreciated that there are similar phases in pre
      clinical development. These consist of 'Phase I' the initial, normally Research
      Discovery driven pharmacology; 'Phase II' non-good laboratory practice (GLP) dose
      range finding, followed by pivotal 'Phase III' GLP toxicology. Together with an
      array of in vitro experiments comparing species, these stages should enable an
      integrated safety assessment prior to entry into man, documenting to
      investigators and authorities evidence that the new pharmaceutic is unlikely to
      cause harm. Following the lessons learned from TeGenero TGN1412 and subsequent
      updates to regulatory guidelines, there are aspects peculiar to biotherapeutics,
      especially those that target key body systems, where calculations could be made
      for doses for human studies using pharmacokinetic and pharmacodynamic models. Two
      of these are exemplified in this paper. In the first, target-mediated drug
      disposition, where the binding of the drug to a cellular target quantitatively
      affects the pharmacokinetics, enables occupancy to be estimated without recourse
      to independent assays. In the second, assaying captured soluble target, as drug
      target complexes, allows estimation of the concentration of the free ligand
      ensuring that in initial clinical studies, soluble targets are not overly
      suppressed. To support this methodology, it has been demonstrated using
      omalizumab, free and total IgE data that such analyses do predict the suppression
      of the free unbound ligand with reasonable accuracy. Overall, the objective of
      the process is to deliver a justification, through consideration of drug-target
      binding, of a safe starting and therapeutically relevant escalation doses for
      human studies.

PMID- 20050848
TI  - Fluoxetine induces apoptosis in ovarian carcinoma cell line OVCAR-3 through
      reactive oxygen species-dependent activation of nuclear factor-kappaB.
AB  - The apoptotic effect of fluoxetine (FLX), an antidepressant, against human
      epithelial ovarian cancer cell lines OVCAR-3 and SK-OV-3 was investigated in
      relation to the mitochondria-mediated cell death process and nuclear factor (NF)
      kappaB activation. FLX-induced mitochondrial membrane permeability change and
      formation of reactive oxygen species, leading to cell death. FLX-induced increase
      in mitochondrial Bax levels, decrease in cytosolic Bid and Bcl-2 levels, loss of
      the mitochondrial transmembrane potential, cytochrome c release, caspase-3
      activation and up-regulation of p53. Oxidant scavengers and Bay 11-7085 [an
      inhibitor of nuclear factor kappaB (NF-kappaB) activation] prevented the FLX
      induced cell death, increase in phosphorylated inhibitory kappaB-alpha and NF
      kappaB p65 levels, and binding of NF-kappaB p65 to DNA. Results from this study
      suggest that FLX may exhibit apoptotic effect against ovarian cancer cell lines
      by inducing the mitochondrial membrane permeability change, which leads to
      cytochrome c release and subsequent caspase-3 activation, through reactive oxygen
      species-dependent activation of NF-kappaB.

PMID- 20050849
TI  - Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory
      activity in vitro and in a model of psoriasis.
AB  - BACKGROUND AND PURPOSE: Apremilast is an orally administered phosphodiesterase-4
      inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic
      inflammatory diseases. The inhibitory effects of apremilast on pro-inflammatory
      responses of human primary peripheral blood mononuclear cells (PBMC),
      polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes
      were explored in vitro, and in a preclinical model of psoriasis. EXPERIMENTAL
      APPROACH: Apremilast was tested in vitro against endotoxin- and superantigen
      stimulated PBMC, bacterial peptide and zymosan-stimulated polymorphonuclear
      cells, immunonoglobulin and cytokine-stimulated NK cells, and ultraviolet B light
      activated keratinocytes. Apremilast was orally administered to beige-severe
      combined immunodeficient mice, xenotransplanted with normal human skin and
      triggered with human psoriatic NK cells. Epidermal skin thickness, proliferation
      index and inflammation markers were analysed. KEY RESULTS: Apremilast inhibited
      PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon-gamma
      and tumour necrosis factor (TNF)-alpha, and interleukins (IL)-2, IL-12 and IL-23.
      Production of TNF-alpha by NK cells and keratinocytes was also inhibited. In
      vivo, apremilast significantly reduced epidermal thickness and proliferation,
      decreased the general histopathological appearance of psoriasiform features and
      reduced expression of TNF-alpha, human leukocyte antigen-DR and intercellular
      adhesion molecule-1 in the lesioned skin. CONCLUSIONS AND IMPLICATIONS:
      Apremilast displayed a broad pattern of anti-inflammatory activity in a variety
      of cell types and decreased the incidence and severity of a psoriasiform response
      in vivo. Inhibition of TNF-alpha, IL-12 and IL-23 production, as well as NK and
      keratinocyte responses by this phosphodiesterase-4 inhibitor suggests a novel
      approach to the treatment of psoriasis.

PMID- 20050850
TI  - Stimulation of adenosine A(2B) receptors induces interleukin-6 secretion in
      cardiac fibroblasts via the PKC-delta-P38 signalling pathway.
AB  - BACKGROUND AND PURPOSE: Inflammatory response and cytokine activation are
      markedly stimulated after myocardial infarction, and contribute to cardiac
      remodelling. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic
      effects on cardiac remodelling. Adenosine, released by all cell types, binds to a
      class of G protein-coupled receptors to induce various cardiovascular effects.
      The aim of this work was to investigate whether activation of adenosine
      receptors, particularly A(2B) adenosine receptors, could stimulate IL-6 secretion
      in cardiac fibroblasts (CFs). EXPERIMENTAL APPROACH: elisa was used to assess IL
      6 concentration in supernatant, and immunostaining was used to analyse IL-6
      protein level in CFs. The levels of phosphorylated and total p38, extracellular
      signal-regulated kinase, c-Jun N-terminal kinase and protein kinase C-delta (PKC
      delta) were determined by Western blot analysis. KEY RESULTS: Adenosine-5'-N
      ethyluronamide (NECA), a stable adenosine analogue, dose- and time-dependently
      stimulated IL-6 secretion in CFs. The effect of NECA was dose-dependently
      inhibited by an A(2B) antagonist, and silencing of the A(2B) receptor also
      inhibited IL-6 secretion. By using PKC isoform-selective inhibitors and
      translocation peptide inhibitors, the PKC-delta isoform was found to be involved
      in the up-regulation of IL-6 production. Inhibition of p38 by SB203580, and
      adenoviral transfer of dominant-negative p38 inhibited NECA-induced IL-6
      production. Furthermore, PKC-delta functioned as an upstream regulator of p38
      MAPK in this process. CONCLUSIONS AND IMPLICATIONS: We demonstrated a novel
      relationship between adenosine and IL-6 secretion, in that IL-6 secretion induced
      by NECA was mediated by adenosine A(2B) receptor activation in CFs and was
      dependent on a PKCdelta-P38 pathway.

PMID- 20050851
TI  - The intermediate conductance Ca2+-activated K+ channel inhibitor TRAM-34
      stimulates proliferation of breast cancer cells via activation of oestrogen
      receptors.
AB  - BACKGROUND AND PURPOSE: K(+) channels play a role in the proliferation of cancer
      cells. We have investigated the effects of specific K(+) channel inhibitors on
      basal and oestrogen-stimulated proliferation of breast cancer cells. EXPERIMENTAL
      APPROACH: Using the mammary adenocarcinoma cell line MCF-7 we assayed cell
      proliferation by radiolabelled thymidine incorporation in the absence or presence
      of various K(+) channel inhibitors with or without 17beta-oestradiol. KEY
      RESULTS: Inhibitors of K(v)10.1 and K(Ca)3.1 K(+) channels suppressed basal
      proliferation of MCF-7 cells, but not oestrogen-stimulated proliferation. TRAM
      34, a specific inhibitor of K(Ca)3.1 channels increased or decreased cell
      proliferation depending on the concentration. At intermediate concentrations (3
      10 microM) TRAM-34 increased cell proliferation, whereas at higher concentrations
      (20-100 microM) TRAM-34 decreased cell proliferation. The enhancement of cell
      proliferation caused by TRAM-34 was blocked by the oestrogen receptor antagonists
      ICI182,780 and tamoxifen. TRAM-34 also increased progesterone receptor mRNA
      expression, decreased oestrogen receptor-alpha mRNA expression and reduced the
      binding of radiolabelled oestrogen to MCF-7 oestrogen receptor, in each case
      mimicking the effects of 17beta-oestradiol. CONCLUSIONS AND IMPLICATIONS: Our
      results demonstrate that K(+) channels K(v)10.1 and K(Ca)3.1 play a role in
      basal, but not oestrogen-stimulated MCF-7 cell proliferation. TRAM-34, as well as
      inhibiting K(Ca)3.1, directly interacts with the oestrogen receptor and mimics
      the effects of 17beta-oestradiol on MCF-7 cell proliferation and gene modulation.
      Our finding that TRAM-34 is able to activate the oestrogen receptor suggests a
      novel action of this supposedly specific K(+) channel inhibitor and raises
      concerns of interpretation in its use.

PMID- 20050852
TI  - Quercetin and its major metabolites selectively modulate cyclic GMP-dependent
      relaxations and associated tolerance in pig isolated coronary artery.
AB  - BACKGROUND AND PURPOSE: Quercetin is a major flavonoid that contributes to the
      reduced risk of cardiovascular disease associated with dietary ingestion of
      fruits and vegetables. We have pharmacologically characterized the effect of
      quercetin, and its sulphate and glucuronide metabolites, on vasoconstrictor and
      vasodilator responses in the porcine isolated coronary artery. EXPERIMENTAL
      APPROACH: Segments of the porcine coronary artery were prepared for either
      isometric tension recording or determination of cyclic GMP content. The effect of
      quercetin and metabolites on submaximal responses to U46619 was examined in the
      presence and absence of substance P, bradykinin, forskolin, sodium nitroprusside
      (SNP) and glyceryl trinitrate (GTN). KEY RESULTS: Quercetin and quercetin 3'
      sulphate inhibited endothelin and U46619-induced contractions with greater
      potency (three- to fivefold) against the former, while quercetin 3-glucoronide
      was inactive. Quercetin enhanced both the cyclic GMP content of the artery
      (threefold) and cyclic GMP-dependent relaxations to GTN and SNP (two to
      threefold), but forskolin-induced relaxations were unaffected. Although the
      effect of quercetin was qualitatively similar to that noted for UK-114,542, a
      selective inhibitor of phosphodiesterase 5, it was still evident against SNP
      induced relaxations in the presence of 10 nM UK-114,542. Quercetin and quercetin
      3'-sulphate significantly reduced the development of GTN-associated 'tolerance'.
      CONCLUSIONS AND IMPLICATIONS: Quercetin and quercetin 3'-sulphate inhibited
      receptor-mediated contractions of the porcine isolated coronary artery by an
      endothelium-independent action. Quercetin selectively enhanced cyclic-GMP
      dependent relaxations by a mechanism not involving phosphodiesterase 5
      inhibition. In addition, quercetin and quercetin 3'-sulphate opposed GTN-induced
      tolerance in vitro, which may be beneficial for patients treated for angina
      pectoris.

PMID- 20050853
TI  - Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs
      targeting vascular diseases.
AB  - Platelet inhibitors are the mainstay treatment for patients with vascular
      diseases. The current 'gold standard' antiplatelet agent clopidogrel has several
      pharmacological and clinical limitations that have prompted the search for more
      effective platelet antagonists. The candidates include various blockers of the
      purinergic P2Y12 receptor such as prasugrel, an oral irreversible thienopyridine;
      two adenosine triphosphate analogues that bind reversibly to the P2Y12 receptor:
      ticagrelor (oral) and cangrelor (intravenous); elinogrel, a direct-acting
      reversible P2Y12 receptor inhibitor (the only antiplatelet compound that can be
      administered both intravenously and orally); BX 667, an orally active and
      reversible small-molecule P2Y12 receptor antagonist; SCH 530348, SCH 205831, SCH
      602539 and E5555, highly selective and orally active antagonists on the protease
      activated receptor 1. A number of drugs also hit new targets: terutroban, an
      oral, selective and specific inhibitor of the thromboxane receptor; ARC1779, a
      second-generation, nuclease resistant aptamer which inhibits von Willebrand
      factor-dependent platelet aggregation; ALX-0081, a bivalent humanized nanobody
      targeting the GPIb binding site of von Willebrand factor and AJW200, an IgG4
      monoclonal antibody of von Willebrand factor. The pharmacology and clinical
      profiles of new platelet antagonists indicate that they provide more consistent,
      more rapid and more potent platelet inhibition than agents currently used.
      Whether these potential advantages will translate into clinical advantages will
      require additional comparisons in properly powered, randomized, controlled
      trials.

PMID- 20050854
TI  - P2Y receptors and atherosclerosis in apolipoprotein E-deficient mice.
AB  - BACKGROUND AND PURPOSE: P2Y nucleotide receptors are involved in the regulation
      of vascular tone, smooth muscle cell (SMC) proliferation and inflammatory
      responses. The present study investigated whether they are involved in
      atherosclerosis. EXPERIMENTAL APPROACH: mRNA of P2Y receptors was quantified (RT
      PCR) in atherosclerotic and plaque-free aorta segments of apolipoprotein E
      deficient (apoE(-/-)) mice. Macrophage activation was assessed in J774
      macrophages, and effects of non-selective purinoceptor antagonists on
      atherosclerosis were evaluated in cholesterol-fed apoE(-/-) mice. KEY RESULTS:
      P2Y(6) receptor mRNA was consistently elevated in segments with atherosclerosis,
      whereas P2Y(2) receptor expression remained unchanged. Expression of P2Y(1) or
      P2Y(4) receptor mRNA was low or undetectable, and not influenced by
      atherosclerosis. P2Y(6) mRNA expression was higher in cultured J774 macrophages
      than in cultured aortic SMCs. Furthermore, immunohistochemical staining of
      plaques demonstrated P2Y(6)-positive macrophages, but few SMCs, suggesting that
      macrophage recruitment accounted for the increase in P2Y(6) receptor mRNA during
      atherosclerosis. In contrast to ATP, the P2Y(6)-selective agonist UDP increased
      mRNA expression and activity of inducible nitric oxide synthase and interleukin-6
      in J774 macrophages; this effect was blocked by suramin (100-300 microM) or
      pyridoxal-phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS, 10-30 microM).
      Finally, 4-week treatment of cholesterol-fed apoE(-/-) mice with suramin or PPADS
      (50 and 25 mg.kg(-1).day(-1) respectively) reduced plaque size, without changing
      plaque composition (relative SMC and macrophage content) or cell replication.
      CONCLUSIONS AND IMPLICATIONS: These results suggest involvement of nucleotide
      receptors, particularly P2Y(6) receptors, during atherosclerosis, and warrant
      further research with selective purinoceptor antagonists or P2Y(6) receptor
      deficient mice.

PMID- 20050855
TI  - A pyoderma gangrenosum following breast reconstruction: a rare cause of skin
      necrosis.

PMID- 20050856
TI  - Optimizing remission rates using antithyroid drugs for Graves' disease.

PMID- 20050857
TI  - Association of vitamin D status with serum androgen levels in men.
AB  - OBJECTIVE: Studies in rodents indicate a role of vitamin D in male reproduction,
      but the relationship between vitamin D and androgen levels in men is largely
      unexplored. We aimed to investigate the association of 25-hydroxyvitamin D
      [25(OH)D] levels with testosterone, free androgen index (FAI) and SHBG. Moreover,
      we examined whether androgen levels show a similar seasonal variation to 25(OH)D.
      DESIGN: In this cross-sectional study, 25(OH)D, testosterone and SHBG levels were
      assessed by immunoassay in 2299 men who were routinely referred for coronary
      angiography (1997-2000). MEASUREMENTS: Main outcome measures were associations of
      25(OH)D levels with testosterone, SHBG and FAI. FAI was calculated as
      testosterone (nmol/l)/SHBG (nmol/l) x 100. RESULTS: Men with sufficient 25(OH)D
      levels (> or =30 microg/l) had significantly higher levels of testosterone and
      FAI and significantly lower levels of SHBG when compared to 25(OH)D insufficient
      (20-29.9 microg/l) and 25(OH)D-deficient (<20 microg/l) men (P < 0.05 for all).
      In linear regression analyses adjusted for possible confounders, we found
      significant associations of 25(OH)D levels with testosterone, FAI and SHBG levels
      (P < 0.05 for all). 25(OH)D, testosterone and FAI levels followed a similar
      seasonal pattern with a nadir in March (12.2 microg/l, 15.9 nmol/l and 40.8,
      respectively) and peak levels in August (23.4 microg/l, 18.7 nmol/l and 49.7,
      respectively) (P < 0.05 for all). CONCLUSION: Androgen levels and 25(OH)D levels
      are associated in men and reveal a concordant seasonal variation. Randomized
      controlled trials are warranted to evaluate the effect of vitamin D
      supplementation on androgen levels.

PMID- 20050858
TI  - The doctor and the detective.

PMID- 20050859
TI  - The continuum of growth hormone-IGF-I axis defects causing short stature:
      diagnostic and therapeutic challenges.
AB  - The growth hormone (GH)-IGF-I axis is essential for normal foetal and childhood
      growth. Defects at different sites in the axis frequently result in short stature
      which may compromise adult height. We describe a continuum of clinically relevant
      abnormalities from GH deficiency through to GH resistance and discuss the
      implementation and interpretation of investigations. We consider appropriate
      therapy for patients with abnormal auxology and subnormal adult height prognosis,
      highlighting new data to clarify therapeutic choices leading to optimal clinical
      outcome.

PMID- 20050860
TI  - Usefulness of iodine/creatinine ratio from spot-urine samples to evaluate the
      effectiveness of low-iodine diet preparation for radioiodine therapy.
AB  - OBJECTIVE: The success of a low-iodine diet (LID) is best determined by
      measurement of 24-h urine iodine (U-I) excretion. The aim of this study was to
      determine reliable estimates for 24-h U-I based on spot-urine samples and to
      provide cut-offs to determine the effectiveness of LID preparation. DESIGN: We
      prospectively measured iodine levels in 193 patients based on 24-h- and spot
      urine samples before radioactive iodine therapy. The iodine was expressed as the
      24-h U-I excretion (microg/day) and as two different indices from spot urine,
      simple iodine concentration (simple I) and the iodine/creatinine (I/Cr) ratio.
      Poor LID preparation was defined as I excretion of >150 microg/day according to
      the 24-h U-I measurement. RESULTS: The measured 24-h U-I was significantly higher
      than the two indices from spot urine (P < 0.001). However, there were
      statistically significant correlations between the 24-h U-I values and the two
      spot-urine-based indices; the correlation coefficient was 0.539 for simple I and
      0.773 for I/Cr ratio (P < 0.001). The cut-off of I/Cr ratio for poor LID
      preparation was >66.2 microg/g Cr (sensitivity 96.4%, specificity 83.6%, positive
      predictive value 50.0% and negative predictive value 99.3%). CONCLUSIONS: We
      demonstrated that the I/Cr ratio from spot urine could serve as a useful and
      reliable alternative to 24-h urine collection as it has acceptable diagnostic
      values for detecting poor LID preparation.

PMID- 20050861
TI  - Change of symptoms and perceived health in acromegalic patients on pegvisomant
      therapy: a retrospective cohort study within the German Pegvisomant Observational
      Study (GPOS).
AB  - OBJECTIVE: This study aimed at investigating how symptoms and perceived health
      changes in acromegalic patients during pegvisomant treatment in respect to IGF-1
      levels and disease characteristics. DESIGN/PATIENTS: Retrospective, multicentre
      cohort study in 131 acromegalic patients within the German Pegvisomant
      Observational Study (GPOS). MEASUREMENTS: Outcome measure was the change of
      perceived health evaluated by the Patient-Assessed Acromegaly Symptom
      Questionnaire (PASQ) between baseline and after 1 year of pegvisomant therapy.
      Predictors were change in IGF-1 levels, maximal pegvisomant dosage, adverse
      events and comorbidities. RESULTS: Perspiration, soft tissue swelling and
      perceived health improved after 1 year of pegvisomant therapy while other
      symptoms such as headache, fatigue and joint pain remained largely unchanged over
      time. The highest mean IGF-1/upper limit of normal (ULN) values before
      pegvisomant therapy were found in those patients with a reported amelioration in
      perspiration and soft tissue swelling after 1 year of pegvisomant treatment. The
      highest mean decrease of IGF-1/ULN was found in those patients with reported
      amelioration of numbness and tingling of limbs. Other factors such as decrease in
      fasting glucose may play a role as independent predictor for some symptoms such
      as the improvement of headache, perspiration and perceived health, while other
      factors such as maximal pegvisomant dosage, occurrence of adverse events, tumour
      growth, or liver enzyme elevation did not play a predictive role. CONCLUSIONS:
      Patients' symptoms and perceived health are in part an independent construct, not
      merely reflecting IGF-1 status or biochemical control. Subjective measures should
      therefore be regularly documented in acromegalic patients as a patient-oriented
      indicator for treatment success.

PMID- 20050862
TI  - Visceral adiposity is closely correlated with neck circumference and represents a
      significant indicator of insulin resistance in WHO grade III obesity.
AB  - OBJECTIVE: Although associations between visceral adiposity (intra-abdominal fat
      mass) and insulin resistance are well established, previous data include few
      subjects with WHO grade III obesity [body mass index (BMI) > 40 kg/m(2)]. We have
      investigated the relationship between visceral adiposity and insulin resistance
      using computed tomography (CT)-quantified fat mass and the homeostasis model
      assessment for insulin resistance (HOMA-IR) in patients with severe obesity.
      PATIENTS AND METHODS: Eighteen nondiabetic subjects with BMI > 40 kg/m(2) were
      recruited. BMI, and waist, hip and neck circumferences were measured. Fasting
      plasma insulin and glucose were measured to calculate HOMA-IR. A single slice CT
      scan was taken at L4 and visceral and abdominal subcutaneous adipose tissue (VAT
      and ASAT, respectively) quantified using 'SliceOmatic' image analysis software.
      RESULTS: A close correlation was demonstrated between VAT and HOMA-IR (r(2) =
      0.46, P = 0.002), whereas ASAT showed no relationship. Neck circumference
      correlated with both VAT (r(2) = 0.67, P < 0.0001) and HOMA-IR (r(2) = 0.35, P =
      0.01). Waist circumference only correlated significantly with VAT (r(2) = 0.25, P
      = 0.03). CONCLUSIONS: Visceral adiposity remains a strongly significant indicator
      of insulin resistance in WHO grade III obesity. Neck circumference surpasses
      other anthropometric measurements as a powerful marker of both VAT and insulin
      resistance.

PMID- 20050863
TI  - Oral uracil-tegafur plus leucovorin vs fluorouracil bolus plus leucovorin for
      advanced colorectal cancer: a meta-analysis of five randomized controlled trials.
AB  - AIM: The aim of this study was to evaluate systematically the efficacy and safety
      of oral uracil-tegafur (UFT) plus leucovorin (LV) compared with infusional
      fluorouracil (5-FU) plus LV for advanced colorectal cancer. METHOD: Eligible
      studies were identified from Medline, Embase and the Cochrane Library. The end
      points included overall survival and overall tumour response rate, and toxicity
      including leucopenia, febrile neutropenia, stomatitis/mucositis and diarrhoea.
      RESULTS: Five randomized controlled trials were identified. Pooled data
      demonstrated no difference in overall survival between the oral UFT plus LV
      regimen and the 5-FU bolus plus LV regimen [hazard ratio 1.013; 95% confidence
      interval (CI) 0.911-1.127].The fixed-effect pooled estimate for overall tumour
      response rate showed no significant difference between the two regimens (relative
      risk 0.893; 0.672-1.187). Grade 3-4 leucopenia [odds ratio (OR) 0.126; 955 CI
      0.048-0.326], grade 1-4 leucopenia (OR 0.089; 95% CI 0.067-0.119) and grade1-4
      febrile neutropenia (OR 0.020; 95% CI 0.004-0.102) were significantly less
      prominent in the oral UFT regimens. For nonhaematological toxicities, grade 3-4
      stomatitis/mucositis (OR 0.075; 95% CI 0.039-0.146), grade 3-4 infection (OR
      0.484; 95% CI 0.310-0.758), grade 1-4 infection (OR 0.672; 95% CI 0.547-0.826, P
      < 0.001), grade 1-4 diarrhoea (OR 0.743; 95% CI 0.626-0.881) were also less
      likely to happen in patients in the oral UFT plus LV regimen, while there was no
      significant difference between the two treatment regimens with respect to grade 1
      4 stomatitis/mucositis (OR 0.278; 95% CI 0.053-1.456) and grade 3-4 (OR 1.174;
      95% CI 0.983-1.403) diarrhoea. CONCLUSION: Oral UFT or 5-FU bolus combined with
      LV results in similar overall survival and tumour response rates for advanced
      colorectal cancer. The former treatment regimen is greatly superior in terms of
      toxicity, especially haematological toxicity.

PMID- 20050864
TI  - Second lineage of heart forming region provides new understanding of conotruncal
      heart defects.
AB  - Abnormal heart development causes various congenital heart defects. Recent
      cardiovascular biology studies have elucidated the morphological mechanisms
      involved in normal and abnormal heart development. The primitive heart tube
      originates from the lateral-most part of the heart forming mesoderm and mainly
      gives rise to the left ventricle. Then, during the cardiac looping, the outflow
      tract is elongated by the addition of cardiogenic cells from the both pharyngeal
      and splanchnic mesoderm (corresponding to anterior and secondary heart field,
      respectively), which originate from the mediocaudal region of the heart forming
      mesoderm and are later located anteriorly (rostrally) to the dorsal region of the
      heart tube. Therefore, the heart progenitors that contribute to the outflow tract
      region are distinct from those that form the left ventricle. The knowledge that
      there are two different lineages of heart progenitors in the four-chambered heart
      provides new understanding of the morphological and molecular etiology of
      conotruncal heart defects.

PMID- 20050865
TI  - Prey diversity is associated with weaker consumer effects in a meta-analysis of
      benthic marine experiments.
AB  - A rapidly accumulating body of research has shown that species diversity
      consistently affects the functioning of ecosystems. The incorporation of trophic
      complexity and the extension of this research to larger scales and natural ranges
      in species diversity remain as important challenges for understanding the true
      magnitude of these effects in natural systems. Here, we test whether the
      diversity of prey communities affects the magnitude of aggregate consumer
      effects. We conducted a meta-analysis of 57 consumer removal field experiments
      from a range of intertidal and subtidal hard substrate marine communities. We
      found that the richness of the prey community was the strongest predictor of the
      magnitude of consumer effects while controlling for habitat type, taxonomic
      composition, and other variables. Consumer removal increased aggregate prey
      abundance on average by 1200% at the lower limit of prey diversity (two species),
      but only 200% at the upper limit of 37 species. Importantly, compositional change
      was substantial at both high and low prey diversity, suggesting predation
      intensity did not vary with prey richness. Rather diverse prey communities appear
      to be more capable of maintaining abundance via compensatory responses, by
      containing prey species that are resistant to (or tolerant of) predators. These
      results suggest that the effects of species diversity on trophic interactions may
      scale consistently from small-scale manipulations to cross-community comparisons.

PMID- 20050866
TI  - A simultaneous test of trophic interaction models: which vegetation
      characteristic explains herbivore control over plant community mass?
AB  - Predicting herbivore control over plants (i.e. changes in plant mass due to
      herbivore damage) is a central goal of ecology. Progress has been limited,
      however, because the vegetation characteristics thought to influence herbivore
      control are naturally correlated and typically experimentally confounded. To
      address this problem, we defined eight conventional models that predict herbivore
      control over plant community mass, each model based on a different vegetation
      characteristic (i.e. host concentration, tissue nitrogen, growth rate, size,
      tolerance of herbivory or net primary productivity). We then used structural
      equation modelling to test each model against two field experiments. Our results
      clearly rejected all models except for a tolerance of herbivory mechanism; stems
      with greater access to limiting resources better tolerated herbivory, regardless
      of where herbivore activity was greatest. Consequently, herbivore reductions of
      plant community mass were greatest at low resource availability. This adds to
      evidence that herbivore activity poorly predicts herbivore control.

PMID- 20050868
TI  - Metabolic responses of novel cellulolytic and saccharolytic agricultural soil
      Bacteria to oxygen.
AB  - Cellulose is the most abundant biopolymer in terrestrial ecosystems and is
      degraded by microbial communities in soils. However, relatively little is known
      about the diversity and function of soil prokaryotes that might participate in
      the overall degradation of this biopolymer. The active cellulolytic and
      saccharolytic Bacteria in an agricultural soil were evaluated by 16S rRNA (13)C
      based stable isotope probing. Cellulose, cellobiose and glucose were mineralized
      under oxic conditions in soil slurries to carbon dioxide. Under anoxic
      conditions, these substrates were converted primarily to acetate, butyrate,
      carbon dioxide, hydrogen and traces of propionate and iso-butyrate; the
      production of these fermentation end-products was concomitant with the apparent
      reduction of iron(III). [(13)C]-cellulose was mainly degraded under oxic
      conditions by novel family-level taxa of the Bacteroidetes and Chloroflexi, and a
      known family-level taxon of Planctomycetes, whereas degradation under anoxic
      conditions was facilitated by the Kineosporiaceae (Actinobacteria) and cluster
      III Clostridiaceae and novel clusters within Bacteroidetes. Active aerobic sub
      communities in oxic [(13)C]-cellobiose and [(13)C]-glucose treatments were
      dominated by Intrasporangiaceae and Micrococcaceae (Actinobacteria) whereas
      active cluster I Clostridiaceae (Firmicutes) were prevalent in anoxic treatments.
      A very large number (i.e. 28) of the detected taxa did not closely affiliate with
      known families, and active Archaea were not detected in any of the treatments.
      These collective findings suggest that: (i) a large uncultured diversity of soil
      Bacteria was involved in the utilization of cellulose and products of its
      hydrolysis, (ii) the active saccharolytic community differed phylogenetically
      from the active cellulolytic community, (iii) oxygen availability impacted
      differentially on the activity of taxa and (iv) different redox guilds (e.g.
      fermenters and iron reducers) compete or interact during cellulose degradation in
      aerated soils.

PMID- 20050869
TI  - RNA binding proteins mediate the ability of a fungus to adapt to the cold.
AB  - Little is known about how fungi adapt to chilling. In eubacteria, cold shock
      proteins (CSPs) facilitate translation by destabilizing RNA secondary structure.
      Animals and plants have homologous cold shock domains within proteins, and
      additional glycine-rich RNA binding proteins (GRPs), but their role in stress
      resistance is poorly understood. In this study, we identified GRP homologues in
      diverse fungi. However, only Aspergillus clavatus and Metarhizium anisopliae
      possessed cold shock domains. Both M. anisopliae's small eubacteria-like CSP
      (CRP1) and its GRP (CRP2) homologue were induced by cold. Disrupting either Crp1
      or Crp2 greatly reduced metabolism and conidial germination rates at low
      temperatures, and decreased tolerance to freezing. However, while both Crp1 and
      Crp2 reduced freezing-induced production of reactive oxygen species, only Crp1
      protected cells against H(2)O(2) and increased M. anisopliae's virulence to
      caterpillars. Unlike CRP2, CRP1 rescued the cold-sensitive growth defects of an
      Escherichia coli CSP deletion mutant, and CRP1 also demonstrated transcription
      anti-termination activity, so CRP1 can regulate transcription and translation at
      low temperature. Expressing either Crp1 or Crp2 in yeast increased metabolism at
      cold temperatures and Crp1 improved tolerance to freezing. Thus besides providing
      a model relevant to many biological systems, Crp1 and Crp2 have potential
      applications in biotechnology.

PMID- 20050870
TI  - Effect of environmental variables on eukaryotic microbial community structure of
      land-fast Arctic sea ice.
AB  - Sea ice microbial community structure affects carbon and nutrient cycling in
      polar seas, but its susceptibility to changing environmental conditions is not
      well understood. We studied the eukaryotic microbial community in sea ice cores
      recovered near Point Barrow, AK in May 2006 by documenting the composition of the
      community in relation to vertical depth within the cores, as well as light
      availability (mainly as variable snow cover) and nutrient concentrations. We
      applied a combination of epifluorescence microscopy, denaturing gradient gel
      electrophoresis and clone libraries of a section of the 18S rRNA gene in order to
      compare the community structure of the major eukaryotic microbial phylotypes in
      the ice. We find that the community composition of the sea ice is more affected
      by the depth horizon in the ice than by light availability, although there are
      significant differences in the abundance of some groups between light regimes.
      Epifluorescence microscopy shows a shift from predominantly heterotrophic life
      styles in the upper ice to autotrophy prevailing in the bottom ice. This is
      supported by the statistical analysis of the similarity between the samples based
      on the denaturing gradient gel electrophoresis banding patterns, which shows a
      clear difference between upper and lower ice sections with respect to phylotypes
      and their proportional abundance. Clone libraries constructed using diatom
      specific primers confirm the high diversity of diatoms in the sea ice, and
      support the microscopic counts. Evidence of protistan grazing upon diatoms was
      also found in lower sections of the core, with implications for carbon and
      nutrient recycling in the ice.

PMID- 20050871
TI  - Identification and characterization of the PhhR regulon in Pseudomonas putida.
AB  - Pseudomonas putida is a soil microorganism that utilizes aromatic amino acids
      present in root exudates as a nitrogen source. We have previously shown that the
      PhhR transcriptional regulator induces phhAB genes encoding a phenylalanine
      hydroxylase. In this study we show, using microarray assays and promoter fusions,
      that PhhR is a global regulator responsible for the activation of genes essential
      for phenylalanine degradation, phenylalanine homeostasis and other genes of
      unknown function. Recently, it has been shown that phenylalanine catabolism
      occurs through more than one pathway. One of these possible pathways involves the
      metabolism of phenylalanine via tyrosine, p-hydroxyphenylpyruvate, and
      homogentisate. We identified two genes within this pathway that encode an acyl
      CoA transferase involved in the metabolism of acetoacetate. All genes in this
      pathway were induced in response to phenylalanine in a PhhR-proficient
      background. The second potential degradative pathway involves the degradation of
      phenylalanine to produce phenylpyruvate, which seems to be degraded via
      phenylacetyl-CoA. A number of mutants in the paa genes encoding phenylacetyl-CoA
      degradation enzymes fail to grow on phenylpyruvate or phenylacetate, further
      supporting the existence of this second pathway. We found that the PhhR regulon
      also includes genes involved in the biosynthesis of aromatic amino acids that are
      repressed in the presence of phenylalanine, suggesting the possibility of
      feedback at the transcriptional level. In addition, we found that PhhR modulates
      the level of expression of the broad-substrate-specificity MexEF/OprN efflux
      pump. Expression from this pump is under the control of mexT gene product because
      phenylalanine-dependent transcription from the mexE promoter does not occur in a
      mexT mutant background. These results place PhhR as an important regulator in the
      control of bacterial responses to aromatic amino acids.

PMID- 20050872
TI  - Interactions between Nosema microspores and a neonicotinoid weaken honeybees
      (Apis mellifera).
AB  - Global pollinators, like honeybees, are declining in abundance and diversity,
      which can adversely affect natural ecosystems and agriculture. Therefore, we
      tested the current hypotheses describing honeybee losses as a multifactorial
      syndrome, by investigating integrative effects of an infectious organism and an
      insecticide on honeybee health. We demonstrated that the interaction between the
      microsporidia Nosema and a neonicotinoid (imidacloprid) significantly weakened
      honeybees. In the short term, the combination of both agents caused the highest
      individual mortality rates and energetic stress. By quantifying the strength of
      immunity at both the individual and social levels, we showed that neither the
      haemocyte number nor the phenoloxidase activity of individuals was affected by
      the different treatments. However, the activity of glucose oxidase, enabling bees
      to sterilize colony and brood food, was significantly decreased only by the
      combination of both factors compared with control, Nosema or imidacloprid groups,
      suggesting a synergistic interaction and in the long term a higher susceptibility
      of the colony to pathogens. This provides the first evidences that interaction
      between an infectious organism and a chemical can also threaten pollinators,
      interactions that are widely used to eliminate insect pests in integrative pest
      management.

PMID- 20050873
TI  - The septal pore cap is an organelle that functions in vegetative growth and
      mushroom formation of the wood-rot fungus Schizophyllum commune.
AB  - Mushroom-forming basidiomycetes colonize large areas in nature. Their hyphae are
      compartmentalized by perforated septa, which are usually covered by a septal pore
      cap (SPC). Here, we describe, for the first time, the composition and function of
      SPCs using the model system Schizophyllum commune. The SPC of S. commune was
      shown to consist of a proteinaceous matrix covered by a lipid membrane. The
      matrix was demonstrated to define the ultrastructure of the SPC and to consist of
      two main proteins, Spc14 and Spc33. Gene spc14 encodes a protein of 86 amino
      acids, which lacks known domain, signal or localization sequences. Gene spc33
      encodes a 239 and a 340 amino acid variant. Both forms contain a predicted signal
      anchor that targets them to the ER. Immuno-localization showed the presence of
      Spc33 in the SPC but not in ER. From this and previous reports it is concluded
      that the SPC is derived from this organelle. Inactivation of spc33 resulted in
      loss of SPCs and the inability to close septa. The latter may well explain why
      vegetative growth and mushroom formation were severely reduced in strains in
      which spc33 was inactivated.

PMID- 20050876
TI  - Streptomycetes contributing to atmospheric molecular hydrogen soil uptake are
      widespread and encode a putative high-affinity [NiFe]-hydrogenase.
AB  - Uptake of molecular hydrogen (H2) by soil is a biological reaction responsible
      for approximately 80% of the global loss of atmospheric H2. Indirect evidence
      obtained over the last decades suggests that free soil hydrogenases with an
      unusually high affinity for H2 are carrying out the reaction. This assumption has
      recently been challenged by the isolation of Streptomyces sp. PCB7, displaying
      the high-affinity H2 uptake activity previously attributed to free soil enzymes.
      While this finding suggests that actinobacteria could be responsible for
      atmospheric H2 soil uptake, the ecological importance of H2-oxidizing
      streptomycetes remains to be investigated. Here, we show that high-affinity H2
      uptake activity is widespread among the streptomycetes. Among 14 streptomycetes
      strains isolated from temperate forest and agricultural soils, six exhibited a
      high-affinity H2 uptake activity. The gene encoding the large subunit of a
      putative high-affinity [NiFe]-hydrogenase (hydB-like gene sequence) was detected
      exclusively in the isolates exhibiting high-affinity H2 uptake. Catalysed
      reporter deposition-fluorescence in situ hybridization (CARD-FISH) experiments
      targeting hydB-like gene transcripts and H2 uptake assays performed with strain
      PCB7 suggested that streptomycetes spores catalysed the H2 uptake activity.
      Expression of the activity in term of biomass revealed that 10(6)-10(7) H2
      oxidizing bacteria per gram of soil should be sufficient to explain in situ H2
      uptake by soil. We propose that specialized H2-oxidizing actinobacteria are
      responsible for the most important sink term in the atmospheric H2 budget.

PMID- 20050875
TI  - Biogeography of wetland rice methanotrophs.
AB  - We focused on the functional guild of methane oxidizing bacteria (MOB) as model
      organisms to get deeper insights into microbial biogeography. The pmoA gene was
      used as a functional and phylogenetic marker for MOB in two approaches: (i) a
      pmoA database (> 4000 sequences) was evaluated to obtain insights into MOB
      diversity in Italian rice paddies, and paddy fields worldwide. The results show a
      wide geographical distribution of pmoA genotypes that seem to be specifically
      adapted to paddy fields (e.g. Rice Paddy Cluster 1 and Rice Paddy Cluster 2).
      (ii) On the smaller geographical scale, we designed a factorial experiment
      including three different locations, two rice varieties and two habitats (soil
      and roots) within each of three rice fields. Multivariate analysis of terminal
      restriction fragment analysis profiles revealed different community patterns at
      the three field sites, located 10-20 km apart. Root samples were characterized by
      high abundance of type I MOB whereas the rice variety had no effect. With the
      agronomical practice being nearly identical, historical contingencies might be
      responsible for the field site differences. Considering a large reservoir of
      viable yet inactive MOB cells acting as a microbial seed bank, environmental
      conditions might have selected and activated a different subset at a time thereby
      shaping the community.

PMID- 20050877
TI  - Iron stores, liver transaminase levels and metabolic risk in healthy teenagers.
AB  - BACKGROUND: Iron overload may contribute to the pathogenesis of insulin
      resistance. We aimed to investigate the relationship among iron stores, liver
      transaminases and components of the metabolic syndrome in healthy teenagers in a
      cross-sectional study. MATERIAL AND METHODS: We determined body mass index (BMI),
      waist-to-hip-ratio (WHR), blood pressure, liver ultrasound, serum lipids,
      insulin, fasting glucose, liver transaminase levels, hsCRP, iron parameters in
      325 of 341 (95.3%) students (234 men, 16.7 +/- 1.7 years; 91 women, 16.5 +/- 1.7
      years) of one single high school. Male and female study participants were
      allocated to increasing quartiles of body iron stores as assessed by
      sTfr/ferritin and alanine aminotranspeptidase (ALT) levels, and the distribution
      of cardiometabolic risk factors along quartiles was analysed. Regression analysis
      was performed to confirm the independent relationship between parameters.
      RESULTS: In male students, BMI, WHR, systolic and diastolic blood pressure, serum
      triglyceride levels and hsCRP were higher in the top sTfR/ferritin and ALT
      quartiles compared with the lowest quartiles (P < 0.01 for all parameters). In
      female students, sTfR/ferritin were not associated with antropomorphic
      cardiometabolic risk factors but with insulin resistance (HOMA-IR, P = 0.046).
      Moreover, ALT levels were independently related to BMI, waist and hip
      circumference, systolic blood pressure, serum triglyceride and insulin
      concentrations (P < 0.05 for all parameters) in female students. CONCLUSION:
      These results provide evidence for linkage among body iron stores, transaminase
      activity and the prevalence of cardiometabolic risk factors in apparently
      healthy, non-obese adolescents even within the range of normal laboratory and
      anthropomorphic values and suggest that iron stores should be investigated as a
      potentially modifiable risk factor in healthy teenagers.

PMID- 20050878
TI  - Elevated serum dehydroepiandrosterone sulphate level correlates with increased
      risk for metabolic syndrome in the elderly men.
AB  - BACKGROUND: The previous studies regarding the association between endogenous
      dehydroepiandrosterone (DHEA) sulphate level and metabolic syndrome are
      inconsistent. This study aimed to investigate such relationship in elderly
      Taiwanese men. MATERIALS AND METHODS: Five hundred and eighty-five elderly
      Taiwanese men (mean age 68.7 +/- 8.3 years) were enrolled as the baseline cohort
      population in 2000. In addition to a questionnaire, body mass index (BMI), blood
      pressure, fasting blood glucose, lipids, albumin and serum DHEA-S levels were
      measured for each participant. Metabolic syndrome was based on the definition by
      the America Heart Association/National Heart Lung Blood Institute. RESULTS: The
      prevalence of metabolic syndrome was 33.3%. Using multivariate logistic
      regression analyses with adjustments for age, smoking, alcohol, physical
      activities, albumin and BMI, there was a positive relationship between serum DHEA
      S level and metabolic syndrome. The highest DHEA-S quartile group had increased
      risk for metabolic syndrome (odds ratio = 2.68, 95% confidence interval: 1.44
      5.01, P < 0.01) compared with the lowest quartile group. The mean serum DHEA-S
      level increased with increasing number of metabolic syndrome components.
      CONCLUSIONS: The prevalence of metabolic syndrome increases with elevated DHEA-S
      levels among elderly Taiwanese men. Thus, elevated serum DHEA-S level should be
      treated as an important risk factor for metabolic syndrome in elderly men.

PMID- 20050879
TI  - Industry sponsorship and selection of comparators in randomized clinical trials.
AB  - BACKGROUND: Most clinical trials on medical interventions are sponsored by the
      industry. The choice of comparators shapes the accumulated evidence. We aimed to
      assess how often major companies sponsor trials that involve only their own
      products. METHODS: Studies were identified by searching ClinicalTrials.gov for
      trials registered in 2006. We focused on randomized trials involving the 15
      companies that had sponsored the largest number of registered trials in
      ClinicalTrials.gov in that period. RESULTS: Overall, 577 randomized trials were
      eligible for analysis and 82% had a single industry sponsor [89% (166/187) of the
      placebo-control trials, 87% (91/105) of trials comparing different doses or ways
      of administration of the same intervention, and 78% (221/285) of other active
      control trials]. The compared intervention(s) belonged to a single company in 67%
      of the trials (89%, 81% and 47% in the three categories respectively). All 15
      companies strongly preferred to run trials where they were the only industry
      sponsor or even the only owner of the assessed interventions. Co-sponsorship
      typically reflected co-ownership of the same intervention by both companies. Head
      to-head comparison of different active interventions developed by different
      companies occurred in only 18 trials with two or more industry sponsors.
      CONCLUSIONS: Each company generates a clinical research agenda that is strongly
      focused on its own products, while comparisons involving different interventions
      from different companies are uncommon. This diminishes the ability to understand
      the relative merits of different interventions for the same condition.

PMID- 20050880
TI  - Alpha-lipoic acid improves vascular endothelial function in patients with type 2
      diabetes: a placebo-controlled randomized trial.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of alpha-lipoic
      acid (ALA) treatment on endothelium-dependent and -independent vasodilatation,
      assessed by forearm blood flow (FBF), in patients with type 2 diabetes mellitus.
      RESEARCH DESIGN AND METHODS: A total of 30 subjects with type 2 diabetes were
      included in this randomized, controlled, double-blinded, parallel group study.
      FBF responses to intra-arterial acetylcholine (ACh) and glycerol trinitrate (GTN)
      were measured before and after 21 days of intravenous treatment with 600 mg alpha
      lipoic acid or placebo. RESULTS: FBF responses were comparable at baseline. After
      treatment, FBF reactivity to ACh and GTN was unchanged in subjects receiving
      placebo. By contrast, ALA treatment increased endothelium-dependent
      vasodilatation to ACh (P < 0.05) but not to GTN compared with baseline.
      CONCLUSIONS: Intravenous ALA treatment improves endothelium-dependent
      vasodilatation in patients with type 2 diabetes, in the absence of effects on
      forearm vasomotor function. If this salutary action translates into vascular risk
      reduction remains to be established.

PMID- 20050881
TI  - Combination of romiplostim and rituximab: effective therapy of severe immune
      thrombocytopenia.

PMID- 20050882
TI  - Over-expression of CCL3 MIP-1alpha in a blastoid mantle cell lymphoma with
      hypercalcemia.
AB  - We analyzed a case with the blastoid variant of mantle cell lymphoma (MCL-BV), a
      rare subtype of B-cell lymphoma, presenting with marked hypercalcemia at
      diagnosis. Enzyme-linked immunosorbent assay (ELISA) showed elevated serum levels
      of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), macrophage
      inflammatory protein-1alpha (MIP-1alpha), and type I collagen telopeptide, but
      not parathyroid hormone, calcitriol or parathyroid hormone-related peptide at
      diagnosis, suggesting local osteoclastic hypercalcemia in this case. By reverse
      transcription polymerase chain reaction (RT-PCR) analysis, we found predominant
      expression of mRNA for MIP-1alpha in addition to those for receptor-activator of
      nuclear-factor kappa B ligand (RANKL), TNF-alpha, and IL-6 in lymphoma cells
      obtained from the patient. Furthermore, recombinant MIP-1alpha significantly
      stimulated (3)H-thymidine uptake by isolated MCL cells in vitro. Treatment with
      intravenous fluids, bisphosphonate, and methylprednisolone followed by
      combination chemotherapy promptly corrects the hypercalcemia and successfully
      induced complete remission, which was accompanied by a decrease of these
      cytokines in the serum, including MIP-1alpha. In the present case, MIP-1alpha, an
      osteoclast-activating factor produced by mantle lymphoma cells, may contribute to
      the development of hypercalcemia. It likely acts through RANKL expression in
      tumor cells and/or stroma cells, as indicated in multiple myeloma (MM) and adult
      T-cell leukemia/lymphoma (ATLL). Furthermore, MIP-1alpha is also involved in the
      development of an aggressive phenotype on MCL by stimulating proliferation of
      these lymphoma cells. In summary, the present study demonstrated that MIP-1alpha
      is an important factor in the development of both hypercalcemia and an aggressive
      phenotype in some types of B-cell lymphoma.

PMID- 20050883
TI  - Paraoxonase 1 (PON1) polymorphisms and risk for essential tremor.
AB  - BACKGROUND: The polymorphic enzyme human serum paraoxonase 1 (PON1), encoded by
      the gene PON1 (chromosome 7q21.3), plays a major role in the metabolism of
      organophosphorus compounds. We investigated the possible association between the
      PON1 genotype and allelic variants of the polymorphisms Leu55Met and Glu192Arg,
      and the risk for essential tremor (ET). METHODS: We studied the frequency of the
      PON1 genotypes and allelic variants in 201 patients with ET and 220 healthy
      controls using a PCR-RLFP method. RESULTS: The frequencies of the PON1 genotypes
      and allelic variants of the polymorphisms Leu55Met and Gln192Arg did not differ
      significantly between patients with ET and controls. These polymorphisms were
      unrelated with the age of onset of ET. CONCLUSIONS: PON1 polymorphisms are not
      related with the risk for ET.

PMID- 20050884
TI  - What constitutes a 'good' recovery outcome in post-acute Guillain-Barre syndrome?
      Results of a nationwide survey of post-acute GBS sufferers in the United Kingdom.
AB  - BACKGROUND: Eighty percent of people with Guillain-Barre Syndrome (GBS) are said
      to achieve 'good' outcome. 'Good' outcome has been defined as either of the top
      two scores (0 = Healthy, 1 = minor symptoms or signs, able to run) on a 7-point
      ordinal scale called the F-score. This assessment of 'good' outcome appears to be
      an arbitrary benchmark. This study is the first assessment of the differences in
      outcome between post-acute GBS sufferers reporting these scores. It attempts to
      compare the physical and emotional differences between respondents reporting '0'
      and '1' on the F-Score. METHODS: A postal survey was administered to respondents
      through the UK Guillain-Barre Syndrome Support Group's national database and
      included items relating to general patient data, general mobility, F-Score,
      Hospital Anxiety and Depression Scale, SF 36 and Fatigue Severity Scale. RESULTS:
      One thousand five hundred and thirty-five members were surveyed, and of 884/1535
      (58%) questionnaires were returned. Results indicate significant differences
      between those scoring '0' on the F-Score and those scoring '1' in the post-acute
      phase in terms of anxiety, depression, physical functioning, fatigue and
      wheelchair use on discharge. CONCLUSIONS: Significantly poorer outcomes for those
      scoring '1' on the F-Score suggest that only those scoring '0' should constitute
      a 'good' outcome in GBS.

PMID- 20050885
TI  - Neurotransmission in Parkinson's disease: beyond dopamine.
AB  - Parkinson's disease (PD) is most frequently associated with characteristic motor
      symptoms that are known to arise with degeneration of dopaminergic neurons.
      However, patients with this disease also experience a multitude of non-motor
      symptoms, such as sleep disturbances, fatigue, apathy, anxiety, depression,
      cognitive impairment, dementia, olfactory dysfunction, pain, sweating and
      constipation, some of which can be at least as debilitating as the movement
      disorders and have a major impact on patients' quality of life. Many of these non
      motor symptoms may be evident prior to the onset of motor dysfunction. The
      neuropathology of PD has shown that complex, interconnected neuronal systems,
      regulated by a number of different neurotransmitters in addition to dopamine, are
      involved in the aetiology of motor and non-motor symptoms. This review focuses on
      the non-dopaminergic neurotransmission systems associated with PD with particular
      reference to the effect that their modulation and interaction with dopamine has
      on the non-motor symptoms of the disease. PD treatments that focus on the
      dopaminergic system alone are unable to alleviate both motor and non-motor
      symptoms, particularly those that develop at early stages of the disease. The
      development of agents that interact with several of the affected
      neurotransmission systems could prove invaluable for the treatment of this
      disease.

PMID- 20050886
TI  - Dural arteriovenous fistula at the foramen magnum presenting with subarachnoid
      hemorrhage: case reports and literature review.
AB  - BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas (DAVFs) may arise at
      any level from the foramen magnum to the sacrum. Only a few case series of DAVFs
      at the foramen magnum have been reported, especially with patients presenting
      with subarachnoid hemorrhage (SAH). We performed a retrospective study of four
      such cases and summarize experiences in the diagnosis and surgical treatment of a
      DAVF at the foramen magnum. METHODS: Four male patients, aged from 35 to 51
      years, were admitted with severe headache. The cranial computerized tomography
      scans of all four patients showed SAH, with hemorrhage in the fourth ventricle
      with or without hemorrhage in the occipital horns of the lateral ventricles. Pre
      operative digital subtraction cerebral angiography showed a DAVF at the foramen
      magnum draining to medullary veins and/or the straight sinus and the confluence
      of sinuses. Two DAVFs were fed by the vertebral artery, whilst the others were
      fed by dural branches of the occipital artery and/or the ascending pharyngeal
      artery. RESULTS: Three patients underwent direct microsurgical electrocoagulation
      and disconnection of the arteriovenous shunt via an enlargement of the foramen
      magnum and a hemilaminectomy at C1 by the far lateral suboccipital approach. Post
      operative angiography confirmed complete obliteration of the fistula.
      CONCLUSIONS: Cerebral digital subtraction angiography is an effective and
      accurate method for examination of a DAVF at the foramen magnum. It can be
      treated effectively and with minimal surgical trauma by microsurgical
      electrocoagulation and disconnection of the shunt.

PMID- 20050887
TI  - Cognitive impairment after three decades of multiple sclerosis.
AB  - BACKGROUND: Population-based studies of cognitive impairment in patients with
      multiple sclerosis (MS) with long disease duration are limited. The aim of this
      study was to evaluate long-term outcome and the predictors of cognitive
      impairment in a cohort of patients with MS. METHODS: Patients living in Oslo,
      Norway, with definite MS and onset in 1940-1980 alive on 1 May 2006 were
      included. Disability was assessed by Expanded Disability Status Scale (EDSS).
      Cognitive functioning was assessed in terms of psychomotor speed, attention,
      learning/memory and executive functions. RESULTS: A total of 123 patients was
      included. EDSS was < or =3.0 in 26% and > or =6.0 in 60% after mean disease
      duration of 34.5 years. Cognitive impairment was found in 48% of the patients
      eligible for neuropsychological evaluation (n = 84). Typical pattern was moderate
      impairment within areas of information processing, attention and memory. In the
      univariate analysis, younger onset age was significantly associated with
      cognitive impairment (P = 0.014). Younger onset age (P = 0.017) and disease
      course (secondary progressive vs. relapsing-remitting MS, P = 0.049) were
      significantly associated with cognitive impairment in the multivariate analysis.
      CONCLUSIONS: After three decades of disease, half of the MS patients experienced
      reduced cognitive functioning; however, nearly one-third of the patients were
      only mildly disabled based on the EDSS. Younger onset age was associated with
      higher prevalence of cognitive impairment. A thorough evaluation of cognitive
      function in addition to EDSS is essential for evaluating long-term impairment in
      patients with MS.

PMID- 20050888
TI  - EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias.
AB  - BACKGROUND AND PURPOSE: These EFNS guidelines on the molecular diagnosis of
      neurogenetic disorders are designed to provide practical help for the general
      neurologist to make appropriate use of molecular genetics in diagnosing
      neurogenetic disorders. METHODS: Literature searches were performed before expert
      members of the task force wrote proposals, which were discussed in detail until
      final consensus had been reached among all task force members. RESULTS AND
      CONCLUSION: This paper provides updated guidelines for molecular diagnosis of two
      particularly complex groups of disorders, the ataxias and spastic paraplegias.
      Possibilities and limitations of molecular genetic diagnosis of these disorders
      are evaluated and recommendations are provided.

PMID- 20050889
TI  - Neurologic complications of Churg-Strauss syndrome--a prospective monocentric
      study.
AB  - BACKGROUND: Churg-Strauss syndrome (CSS) is a rare systemic vasculitis. Case
      series with a focus on neurologic involvement are not common. With this study, we
      intended to evaluate the frequency and types of neurologic manifestations and
      complications at time of diagnosis and during follow-up of patients with CSS.
      METHODS: In this monocentric study, consecutive patients of our hospital with
      first diagnosis of CSS based on the criteria of the American College of
      Rheumatology were included between 2001 and 2007. Each patient underwent a
      periodic follow-up with clinical and electrophysiologic examination. Data were
      obtained prospectively. RESULTS: Fourteen patients were included. All patients
      had a hypereosinophilia and a history of asthma. Twelve of 14 patients had a
      neurologic involvement, mainly as an acute or subacute multiplex mononeuropathy
      (eight patients) or an axonal polyneuropathy (three patients). Three patients
      suffered from a neuropathy of cranial nerves, and two patients had a cerebral
      infarct. Mean follow-up period was 31 months. With immunosuppressive therapy, 13
      patients had no additional neurologic complications, one patient suffered from a
      cerebral infarct. Initial neurologic symptoms as a result of peripheral
      neuropathy improved, but sequelae of axonal damage were persistently detectable.
      CONCLUSIONS: Even at time of diagnosis of a CSS, neurologic manifestations are
      common, especially as a multiplex mononeuropathy. With a consequent
      immunosuppressive therapy, new neurologic complications can be avoided for the
      most part.

PMID- 20050890
TI  - Hyperhomocysteinemia recurrence in levodopa-treated Parkinson's disease patients.
AB  - BACKGROUND: Patients with Parkinson's disease (PD) and chronically treated with L
      DOPA exhibit, in a percentage of 10-30%, supra-physiological levels of plasma
      total homocysteinemia (tHcy). In this study, we have investigated, in a group of
      hyper-homocysteinemic PD patients, the time of hyper-tHcy recurrence after
      discontinuation of 1-month folate supplementation given to normalize plasma tHcy
      levels. METHODS: Plasma tHcy, cobalamin and folate were assayed before and after
      1-month folate supplementation (5 mg/day), and after 2 and 4 months after folate
      discontinuation in 29 PD patients (16M/13F, mean age 69.4 +/- 6.9 years)
      stabilized on a mean L-DOPA dose of 509.4 +/- 312.1 mg/day. RESULTS: After folate
      supplementation, plasma tHcy levels fell within the normal range in all patients.
      At the 2-month control after folate discontinuation, plasma tHcy remained within
      physiological values in 25 out of 29 patients. Conversely, 4 months after folate
      discontinuation, all patients exhibited hyper-tHcy. CONCLUSIONS: One-month intake
      of 5 mg/day folate normalizes plasma tHcy levels in all hyper-homocysteinemic PD
      patients. Following folate discontinuation, hyper-tHcy recurs in all patients
      within 4 months. Knowledge of this time interval is useful to optimize pulses of
      folate therapy in hyper-homocysteinemic patients with PD.

PMID- 20050892
TI  - Comments on 'aspects of peripheral nerve involvement in patients with treated
      hypothyroidism'.

PMID- 20050893
TI  - EFNS guideline on the management of status epilepticus in adults.
AB  - The objective of the current article was to review the literature and discuss the
      degree of evidence for various treatment strategies for status epilepticus (SE)
      in adults. We searched MEDLINE and EMBASE for relevant literature from 1966 to
      January 2005 and in the current updated version all pertinent publications from
      January 2005 to January 2009. Furthermore, the Cochrane Central Register of
      Controlled Trials (CENTRAL) was sought. Recommendations are based on this
      literature and on our judgement of the relevance of the references to the
      subject. Recommendations were reached by informative consensus approach. Where
      there was a lack of evidence but consensus was clear, we have stated our opinion
      as good practice points. The preferred treatment pathway for generalised
      convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4-8
      mg lorazepam or 10 mg diazepam directly followed by 18 mg/kg phenytoin. If
      seizures continue more than 10 min after first injection, another 4 mg lorazepam
      or 10 mg diazepam is recommended. Refractory GCSE is treated by anaesthetic doses
      of barbiturates, midazolam or propofol; the anaesthetics are titrated against an
      electroencephalogram burst suppression pattern for at least 24 h. The initial
      therapy of non-convulsive SE depends on type and cause. Complex partial SE is
      initially treated in the same manner as GCSE. However, if it turns out to be
      refractory, further non-anaesthetising i.v. substances such levetiracetam,
      phenobarbital or valproic acid should be given instead of anaesthetics. In subtle
      SE, in most patients, i.v. anaesthesia is required.

PMID- 20050894
TI  - Chronic cognitive sequelae after traumatic brain injury are not related to growth
      hormone deficiency in adults.
AB  - OBJECTIVE: The objective of the study was to asses the possible influence of
      hypothalamo-pituitary deficiencies, and growth hormone (GH) deficiency in
      particular, on cognition in adult patients with traumatic brain injury (TBI). TBI
      is a recently identified risk factor for cognitive deficits and hypopituitarism.
      Even the patients with favorable outcome after TBI may present with persistent
      bodily, psychosocial, and cognitive impairments, resembling patients with
      untreated partial or complete pituitary insufficiency. DESIGN: We performed
      retrospective and cross-sectional study of endocrine and cognitive function in
      TBI in 61 patients (aged 37.7 +/- 1.7 years) of both sexes (44 m,17 f), at least
      1 year after TBI (3.9 +/- 0.6 years). Serum insulin-like growth factor 1 (IGF-I),
      thyroxin, thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH),
      luteinizing hormone (LH), testosterone (in men), prolactin, and cortisol were
      measured, and GH secretion was assessed by growth hormone releasing hormone
      (GHRH) + growth hormone releasing peptide-6 (GHRP-6) test. Cognitive function was
      assessed by using a standard neuropsychological battery. RESULTS: GH deficiency
      (GHD) and GH insufficiency (GHI) were found in 20 patients (32.8%). After
      adjustment for confounders [age, body mass index (BMI), education level, time
      elapsed from TBI], there were no significant differences in results of
      neuropsychological tests between patients with TBI with GHD, GHI, and normal GH
      secretion. There were no correlations of neuropsychological variables with
      stimulated peak GH secretion or IGF-I level. CONCLUSIONS: GHD persists long after
      the TBI, independently of trauma severity and age at traumatic event. GH
      secretion is more sensitive to TBI than other pituitary hormones. No evidence is
      found for an association of cognitive function impairment and somatotropic axis
      impairment in adult patients tested more than 1 year after the TBI.

PMID- 20050895
TI  - Apraxia contributes to the motor deficit in Parkinson's Disease and multiple
      system atrophy.

PMID- 20050896
TI  - Apraxia in Parkinson's disease and multiple system atrophy.
AB  - OBJECTIVE: To determine praxis function in patients with Parkinson's disease (PD)
      and multiple system atrophy (MSA). METHODS: Nineteen patients with PD and 16
      patients with probable MSA were recruited into study. Twenty-five age-matched,
      healthy subjects were included as controls. The Mayo Clinic praxis test battery
      was applied. Pantomime tasks, including oral/facial, trunk, and upper extremity
      movement, were used to evaluate ideomotor apraxia (IMA). Sequential tasks,
      including Luria test for ideational apraxia (IDA) and use of actual objects, were
      also tested. In addition, Standardized Mini Mental Test (MMSE), Hamilton
      Depression (HAM-D), and Anxiety (HAM-A) Scales were used. RESULTS: Mean ages of
      the study participants were 66 +/- 7, 68 +/- 5, and 65 +/- 7 years in PD, MSA,
      and control groups, respectively. Mean total praxis score was significantly lower
      for patients with PD (92.4 +/- 4) and MSA (75.9 +/- 18) than for controls (97.4
      +/- 2) (P = 0.000). Transitive performances of upper extremities and sequential
      tasks were significantly impaired in patients with PD compared to control
      subjects (P < 0.05). There was no correlation between total praxis scores and sum
      scores of tremor, bradykinesia, and rigidity of both of the upper limbs of
      patients with PD. Subgroup praxis scores were substantially worse in MSA group (P
      < 0.0001). Compared to control subjects, mean scores for MMSE, HAM-D, and HAM-A
      tests were significantly worse in MSA group, but, for PD patient group, only HAM
      A scores were worse. CONCLUSION: Our results indicate that although not a
      presenting symptom, IMA and IDA may be features of MSA and, to a lesser degree,
      of PD. Also, it seems to be unrelated to the motor features of patients with PD.

PMID- 20050897
TI  - Location and severity of spasticity in the first 1-2 weeks and at 3 and 18 months
      after stroke.
AB  - BACKGROUND AND PURPOSE: There is no consensus concerning the location or severity
      of spasticity, or how this changes with time after stroke. The purpose was to
      describe: the location and severity of spasticity, in different muscle groups,
      during the first 1-2 weeks and at 3 and 18 months after stroke; the association
      between the severity of spasticity and control of voluntary movements; and the
      occurrence of spasticity in younger versus older patients. METHODS: In a cohort
      of consecutive patients, the following parameters were assessed during the first
      1-2 weeks (n = 109) and at 3 (n = 95) and 18 (n = 66) months after first-ever
      stroke: spasticity, by the Modified Ashworth Scale in different muscle groups;
      plantar-flexor clonus, by physical examination; and movement function, by the
      Lindmark Motor Assessment Scale. RESULTS: During the first 1-2 weeks and at 3
      months after stroke, spasticity was most common in the anti-gravity muscles. The
      severity of upper extremity spasticity increased over time (P < 0.05). Upper
      extremity spasticity and movement scores were moderately associated (r = -0.61, P
      < 0.05). At 3 months, spasticity was more common amongst the younger patients (P
      < 0.05). CONCLUSIONS: The results confirm that spasticity is most common in the
      anti-gravity muscles and is associated with the control of voluntary movements.
      As the severity of spasticity also increased after 3 months, when neurally
      mediated spasticity is expected to have passed its peak, intrinsic muscle changes
      may play a larger role than neural components with the passage of time after
      stroke.

PMID- 20050898
TI  - Epidural blood patch in Trendelenburg position pre-medicated with acetazolamide
      to treat spontaneous intracranial hypotension.
AB  - BACKGROUND: Spontaneous intracranial hypotension (SIH) is characterized by
      orthostatic headache, diffuse pachymeningeal enhancement on brain magnetic
      resonance imaging (MRI) and low cerebrospinal fluid (CSF) pressure. Treatment
      ranges from conservative management, such as bed rest, overhydration and
      caffeine, to invasive procedures, such as the autologous epidural blood patch
      (EBP), computed tomography (CT)-guided fibrin glue injection at the site of the
      leak and open surgical intervention. EBP has emerged as the treatment of choice
      for SIH when initial conservative measures fail to bring relief. METHODS: Forty
      two patients with SIH were treated with lumbar autologous EBP in Trendelenburg
      position preceded by pre-medication with acetazolamide. RESULTS: A complete
      recovery was obtained in all patients after one (90%), two (5%) or three (5%)
      EBPs. After EBP, two patients (5%) also performed evacuation of bilateral chronic
      subdural hematoma with mass effect. CONCLUSIONS: Spontaneous intracranial
      hypotension can be effectively cured by lumbar autologous EBP in Trendelenburg
      position pre-medicated with acetazolamide.

PMID- 20050899
TI  - The FTLD-modified Clinical Dementia Rating scale is a reliable tool for defining
      disease severity in frontotemporal lobar degeneration: evidence from a brain
      SPECT study.
AB  - BACKGROUND: Frontotemporal Lobar Degeneration (FTLD) is a heterogeneous disorder
      characterized by impairment in executive functions, behavioural disturbance and
      language deficit. Reliable scales of global impairment are under evaluation. A
      consortium of Mayo Clinic and University of California FTLD Centers has recently
      developed the FTLD-modified Clinical Dementia Rating (CDR) scale to assess FTLD
      severity. OBJECTIVE: To evaluate whether FTLD-modified CDR scores correlate with
      the pattern and degree of brain SPECT hypoperfusion in patients with FTLD.
      METHODS: Ninety-nine patients with FTLD entered the study. Patients underwent a
      clinical evaluation and a wide standardized neuropsychological assessment,
      including mini-mental state examination (MMSE) and FTLD-modified CDR. A brain
      SPECT perfusion imaging study was carried out in each patient. A linear
      correlation analysis between frontotemporal dementia-modified CDR or
      neuropsychological tests scores and perfusion data was performed. RESULTS: There
      was a significant relationship between higher FTLD-modified CDR score and lower
      global regional cerebral blood flow in the frontal and temporal lobes,
      bilaterally. No significant correlation between MMSE and brain frontotemporal
      hypoperfusion was found. The correlation between brain hypoperfusion pattern and
      neuropsychological test scores tapping different cognitive domains fitted with
      previously published data. CONCLUSIONS: The recently introduced FTLD-modified CDR
      scale correlates with the degree of frontotemporal hypoperfusion in patients with
      FTLD. This study confirms and further supports the usefulness of FTLD-modified
      CDR in future clinical trials to monitor disease progression.

PMID- 20050900
TI  - Cut-off scores in MMSE: a moving target?
AB  - BACKGROUND: Cognitive tests are known to be influenced by language, culture and
      education. In addition, there may be an impact of 'epoch' in cognition, because
      there is secular increase in scores of IQ tests in children. If we assume this is
      a long lasting process, then it should persist later in life. METHODS: To test
      this hypothesis, we compared the performance of two cohorts of individuals
      (>or=50 years of age), evaluated 20 years apart using the Mini-Mental State
      Examination (MMSE). RESULTS: Study population included 135 participants in 1988
      and 411 in 2008. MMSE scores were higher in 2008 than in 1988 for literacy x age
      matched subgroups, the difference being significant for participants with lower
      literacy. Score variance was explained by literacy (beta = 0.479, t = 14.598, P =
      0.00), epoch (beta = 0.34, t = 10.33, P = 0.00) and age (beta = -0.142, t = 
      4.184, P = 0.00). CONCLUSION: The present results are in accordance with a
      lifelong secular improvement in cognitive performance. The operational cut-off
      values may change with time, which may have clinical impact in the diagnosis of
      disorders like mild cognitive impairment or dementia.

PMID- 20050901
TI  - A new era in acute neurological consultations.

PMID- 20050902
TI  - Neurological manifestations of Churg-Strauss syndrome.

PMID- 20050903
TI  - The 'hidden work' of a hospital neurologist: 1000 consults later.
AB  - BACKGROUND: A new Web-based, internal neurology referral service was introduced
      in our department to expedite inpatient review for other departments and to allow
      assessment of the impact of neurology consults on patient care throughout the
      hospital, especially in the emergency department (ED). The results of the
      analysis of the first 1000 referrals using the new system are presented. METHODS:
      An intranet referral system was designed by the consultant neurologists. The
      previous method of referral was by handwritten letter. The electronic template
      included 'drop-down' menus and mandatory fields to help guide referring teams. An
      outcome section is completed by the neurology team. RESULTS: An average of 17
      referrals was seen weekly. Seventy-seven per cent were seen within 24 h of
      referral. A consultant neurologist saw 87% of the referrals directly; 13% were
      first seen by a registrar and later discussed with a consultant. Forty per cent
      were seen in the ED of which a one-third of the patients were discharged
      following assessment. The most common reason for referral was seizure(s) or an
      episode of collapse (28%). Patients presenting with stroke/transient ischaemic
      attack represented 13.5%, and 12.5% presented with headaches. The management of
      79% of referred cases was deemed to have been significantly changed after
      neurology review. DISCUSSION: The introduction of a neurology consultant-designed
      and consultant-led intranet referral service has greatly enhanced the delivery of
      the consult service to patients in our hospital. This referral system contributes
      significantly to hospital efficiency and to access for patients to specialist
      assessment.

PMID- 20050904
TI  - Differences in nigro-striatal impairment in clinical variants of early
      Parkinson's disease: evidence from a FP-CIT SPECT study.
AB  - INTRODUCTION: In idiopathic Parkinson's disease (PD), two different clinical
      phenotypes are usually distinguished: a tremor dominant variant (TD) and an
      akinetic-rigid type (ART). TD patients are characterized by a slower disease
      progression and a minor cognitive impairment. Striatal density of DAT, as
      quantified by FP-CIT SPECT, has been reported to correlate with rigidity and
      akinesia but not with tremor. OBJECTIVE: To evaluate FP-CIT uptake in TD and ART
      phenotypes. METHODS: We retrospectively evaluated from our database the pre
      synaptic nigro-striatal function of 24 patients with TD-PD and 38 patients with
      ART-PD who underwent a FP-CIT SPECT within 1 year from disease onset. RESULTS:
      Disease duration, age at the time of SPECT scan and disease severity as measured
      with Unified Parkinson's Disease Rating scale part III (UPDRS III) were not
      statistically different between the two groups. Putamen contralateral to the most
      clinically affected side showed a lower FP-CIT uptake in ART patients compared to
      TD patients. No statistically significant differences emerged when considering
      bilateral caudate and ipsilateral putaminal uptake, as well as asymmetry indices
      and caudate/putamen ratios. FP-CIT contralateral putaminal uptake correlated with
      the severity of rigidity and hypokinesia but not with tremor. CONCLUSIONS: These
      data suggest that other neurotransmitter systems apart from the nigro-striatal
      dopaminergic system are involved in the generation of Parkinsonian tremor, and
      they are consistent with previous evidence of a lack of correlation between
      tremor severity and FP-CIT uptake. Putaminal relative sparing in TD patients
      could partially explain the slower disease progression reported in this PD
      phenotype.

PMID- 20050905
TI  - Bioavailability of interferon-beta in patients with multiple sclerosis - fishing
      for the surrogate.

PMID- 20050906
TI  - Neutralizing antibodies, MxA expression and MMP-9/TIMP-1 ratio as markers of
      bioavailability of interferon-beta treatment in multiple sclerosis patients: a
      two-year follow-up study.
AB  - BACKGROUND: The objective of this study was to correlate the detection of
      neutralizing antibodies (NAbs) by the cytopathic effect (CPE) assay, with the
      expression of myxovirus resistance protein A (MxA), and the ratio between matrix
      metalloproteinase 9 (MMP-9) and its tissular inhibitor (TIMP-1), in order to
      evaluate their usefulness as markers of interferon beta (IFN-beta)
      bioavailability. METHODS: Pairs of blood and serum samples were collected from 50
      patients with multiple sclerosis (MS) during 2 years of IFN-beta treatment.
      Expression of MxA, MMP-9 and TIMP-1 were analysed by quantitative PCR, and NAbs
      were measured by CPE assay. RESULTS: During the study, 60% of patients presented
      NAbs. The number of serum samples that were NAbs+ was significantly increased
      amongst patients with relapses (41/92 vs. 33/108, P = 0.04). With one serum
      sample and with a NAb titre >100 tenfold reduction unit (TRU), 66.7% of patients
      with MS suffered from relapses, 41.7% suffered from progression, and 75% was not
      an optimal clinical responder. We did not find any significant difference in MxA.
      We found that 62.5% of patients with MS patients whose ratio was increased
      twofold after 2 years suffered from relapses, 37.5% suffered from progression,
      and 68.7% was not an optimal clinical responder. CONCLUSION: The early detection
      of NAbs by CPE assay and the finding of only one serum sample with a NAb titre
      >100 TRU seem to be markers of low bioavailability of IFN-beta, whilst a twofold
      decrease in the MMP-9/TIMP-1 ratio by quantitative PCR assay seems to be a marker
      of high bioavailability of IFN-beta.

PMID- 20050907
TI  - Data archiving.

PMID- 20050909
TI  - How does spatial dispersal network affect the evolution of parasite local
      adaptation?
AB  - Studying patterns of parasite local adaptation can provide insights into the
      spatiotemporal dynamics of host-parasite coevolution. Many factors, both biotic
      and abiotic, have been identified that influence parasite local adaptation. In
      particular, dispersal and population structuring are considered important
      determinants of local adaptation. We investigated how the shape of the spatial
      dispersal network within experimental landscapes affected local adaptation of a
      bacteriophage parasite to its bacterial host. Regardless of landscape topology,
      dispersal always led to the evolution of phages with broader infectivity range.
      However, when the spatial dispersal network resulted in spatial variation in the
      breadth of phage infectivity range, significant levels of parasite local
      adaptation and local maladaptation were detected within the same landscape using
      the local versus foreign definition of local adaptation. By contrast, local
      adaptation was not detected using the home versus away or local versus global
      definitions of local adaptation. This suggests that spatial dispersal networks
      may play an important role in driving parasite local adaptation, particularly
      when the shape of the dispersal network generates nonuniform levels of host
      resistance or parasite infectivity throughout a species' range.

PMID- 20050910
TI  - Clines in cuticular hydrocarbons in two Drosophila species with independent
      population histories.
AB  - We took a comparative approach utilizing clines to investigate the extent to
      which natural selection may have shaped population divergence in cuticular
      hydrocarbons (CHCs) that are also under sexual selection in Drosophila. We
      detected the presence of CHC clines along a latitudinal gradient on the east
      coast of Australia in two fly species with independent phylogenetic and
      population histories, suggesting adaptation to shared abiotic factors. For both
      species, significant associations were detected between clinal variation in CHCs
      and temperature variation along the gradient, suggesting temperature maxima as a
      candidate abiotic factor shaping CHC variation among populations. However,
      rainfall and humidity correlated with CHC variation to differing extents in the
      two species, suggesting that response to these abiotic factors may vary in a
      species-specific manner. Our results suggest that natural selection, in addition
      to sexual selection, plays a significant role in structuring among-population
      variation in sexually selected traits in Drosophila.

PMID- 20050911
TI  - Alternate pathways of body shape evolution translate into common patterns of
      locomotor evolution in two clades of lizards.
AB  - Body shape has a fundamental impact on organismal function, but it is unknown how
      functional morphology and locomotor performance and kinematics relate across a
      diverse array of body shapes. We showed that although patterns of body shape
      evolution differed considerably between lizards of the Phrynosomatinae and
      Lerista, patterns of locomotor evolution coincided between clades. Specifically,
      we found that the phrynosomatines evolved a stocky phenotype through body
      widening and limb shortening, whereas Lerista evolved elongation through body
      lengthening and limb shortening. In both clades, relative limb length played a
      key role in locomotor evolution and kinematic strategies, with long-limbed
      species moving faster and taking longer strides. In Lerista, the body axis also
      influenced locomotor evolution. Similar patterns of locomotor evolution were
      likely due to constraints on how the body can move. However, these common
      patterns of locomotor evolution between the two clades resulted in different
      kinematic strategies and levels of performance among species because of their
      morphological differences. Furthermore, we found no evidence that distinct body
      shapes are adaptations to different substrates, as locomotor kinematics did not
      change on loose or solid substrates. Our findings illustrate the importance of
      studying kinematics to understand the mechanisms of locomotor evolution and
      phenotype-function relationships.

PMID- 20050912
TI  - Fitness consequences of sex-specific selection.
AB  - Theory suggests that sex-specific selection can facilitate adaptation in sexually
      reproducing populations. However, sexual conflict theory and recent experiments
      indicate that sex-specific selection is potentially costly due to sexual
      antagonism: alleles harmful to one sex can accumulate within a population because
      they are favored in the other sex. Whether sex-specific selection provides a net
      fitness benefit or cost depends, in part, on the relative frequency and strength
      of sexually concordant versus sexually antagonistic selection throughout a
      species' genome. Here, we model the net fitness consequences of sex-specific
      selection while explicitly considering both sexually concordant and sexually
      antagonistic selection. The model shows that, even when sexual antagonism is
      rare, the fitness costs that it imposes will generally overwhelm fitness benefits
      of sexually concordant selection. Furthermore, the cost of sexual antagonism is,
      at best, only partially resolved by the evolution of sex-limited gene expression.
      To evaluate the key parameters of the model, we analyze an extensive dataset of
      sex-specific selection gradients from wild populations, along with data from the
      experimental evolution literature. The model and data imply that sex-specific
      selection may likely impose a net cost on sexually reproducing species, although
      additional research will be required to confirm this conclusion.

PMID- 20050913
TI  - Life history, habitat saturation and the evolution of fecundity and survival
      altruism.
AB  - Hamilton's rule provides a general description of the conditions for the
      evolution of altruism. But altruism can take different forms depending on which
      life-history trait is affected by the helping behavior (fecundity vs. survival
      helping). In particular, these different forms of helping may have very different
      demographic consequences, which may feed back on evolution. We examine the
      interplay between various forms of helping and demography in viscous populations
      with empty sites. A key component of our analysis is the local density of empty
      sites experienced by a focal individual, which provides a measure of habitat
      saturation. Habitat saturation is shown to have contrasting effects depending on
      (1) whether the physiological costs and benefits of helping affect fecundity,
      survival or both; and (2) whether the costs of helping are paid in a density
      dependent or density-independent manner. For a given level of habitat saturation
      and with density-dependent reproduction, we find that the conditions for the
      evolution of helping should be more favorable in the survival altruism life cycle
      with a cost on fecundity, and more stringent in the fecundity altruism life cycle
      with a cost on survival. More generally, our analysis stresses the importance of
      taking into account the feedback between population demography, life history, and
      kin selection when investigating the selective pressures on altruism.

PMID- 20050914
TI  - Sexual conflict and the maintenance of multivariate genetic variation.
AB  - Mate choice should erode additive genetic variation in sexual displays, yet these
      traits often harbor substantial genetic variation. Nevertheless, recent
      developments in quantitative genetics have suggested that multivariate genetic
      variation in the combinations of traits under selection may still be depleted.
      Accordingly, the erosion and maintenance of variation may only be detectable by
      studying whole suites of traits. One potential process favoring the maintenance
      of genetic variance in multiple trait combinations is the modification of sexual
      selection via sexually antagonistic interactions between males and females. Here
      we consider how interlocus sexual conflict can shape the genetic architecture of
      male sexual traits in the cricket, Teleogryllus commodus. In this species, the
      ability of each sex to manipulate insemination success significantly alters the
      selection acting on male courtship call properties. Using a quantitative genetic
      breeding design we estimated the additive genetic variation in these traits and
      then predicted the change in variation due to previously documented patterns of
      sexual selection. Our results indicate that female choice should indeed deplete
      multivariate genetic variance, but that sexual conflict over insemination success
      may oppose this loss of variance. We suggest that changes in the direction of
      selection due to sexually antagonistic interactions will be an important and
      potentially widespread factor in maintaining multivariate genetic variation.

PMID- 20050915
TI  - The dual benefits of aposematism: predator avoidance and enhanced resource
      collection.
AB  - Theories of aposematism often focus on the idea that warning displays evolve
      because they work as effective signals to predators. Here, we argue that
      aposematism may instead evolve because, by enhancing protection, it enables
      animals to become more exposed and thereby gain resource-gathering benefits, for
      example, through a wider foraging niche. Frequency-dependent barriers (caused by
      enhanced conspicuousness relative to other prey and low levels of predator
      education) are generally assumed to make the evolution of aposematism
      particularly challenging. Using a deterministic, evolutionary model we show that
      aposematic display could evolve relatively easily if it enabled prey to move more
      freely around their environments, or become exposed in some other manner that
      provides fitness benefits unrelated to predation risk. Furthermore, the model
      shows that the traits of aposematic conspicuousness and behavior which lead to
      raised exposure positively affect each other, so that the optimal level of both
      tends to increase when the traits exist together, compared to when they exist in
      isolation. We discuss the ecological and evolutionary consequences of
      aposematism. One conclusion is that aposematism could be a key evolutionary
      innovation, because by widening habitat use it may promote adaptive radiation as
      a byproduct of enhanced ecological opportunity.

PMID- 20050916
TI  - Comparing the substrate specificities of cytochrome c biogenesis Systems I and
      II: bioenergetics.
AB  - c-Type cytochromes require specific post-translational protein systems, which
      vary in different organisms, for the characteristic covalent attachment of heme
      to the cytochrome polypeptide. Cytochrome c biogenesis System II, found in
      chloroplasts and many bacteria, comprises four subunits, two of which (ResB and
      ResC) are the minimal functional unit. The ycf5 gene from Helicobacter pylori
      encodes a fusion of ResB and ResC. Heterologous expression of ResBC in
      Escherichia coli lacking its own biogenesis machinery allowed us to investigate
      the substrate specificity of System II. ResBC is able to attach heme to monoheme
      c-type cytochromes c(550) from Paracoccus denitrificans and c(552) from
      Hydrogenobacter thermophilus, both normally matured by System I. The production
      of holocytochrome is enhanced by the addition of exogenous reductant. Single
      cysteine variants of these cytochromes were not efficiently matured by System II,
      but System I was able to produce detectable amounts of AXXCH variants; this adds
      to evidence that there is no obligate requirement for a disulfide-bonded
      intermediate for the latter c-type cytochrome biogenesis system. In addition,
      System II was able to mature an AXXAH-containing variant into a b-type
      cytochrome, with implications for both heme supply to the periplasm and substrate
      recognition by System II.

PMID- 20050917
TI  - Crystal structure of salt-tolerant glutaminase from Micrococcus luteus K-3 in the
      presence and absence of its product L-glutamate and its activator Tris.
AB  - Glutaminase from Micrococcus luteus K-3 [Micrococcus glutaminase (Mglu); 456
      amino acid residues (aa); 48 kDa] is a salt-tolerant enzyme. Our previous study
      determined the structure of its major 42-kDa fragment. Here, using new
      crystallization conditions, we determined the structures of the intact enzyme in
      the presence and absence of its product L-glutamate and its activator Tris, which
      activates the enzyme by sixfold. With the exception of a 'lid' part (26-29 aa)
      and a few other short stretches, the structures were all very similar over the
      entire polypeptide chain. However, the presence of the ligands significantly
      reduced the length of the disordered regions: 41 aa in the unliganded structure
      (N), 21 aa for L-glutamate (G), 8 aa for Tris (T) and 6 aa for both L-glutamate
      and Tris (TG). L-glutamate was identified in both the G and TG structures,
      whereas Tris was only identified in the TG structure. Comparison of the glutamate
      binding site between Mglu and salt-labile glutaminase (YbgJ) from Bacillus
      subtilis showed significantly smaller structural changes of the protein part in
      Mglu. A comparison of the substrate-binding pocket of Mglu, which is highly
      specific for L-glutamine, with that of Erwinia carotovora asparaginase, which has
      substrates other than L-glutamine, shows that Mglu has a larger substrate-binding
      pocket that prevents the binding of L-asparagine with proper interactions.

PMID- 20050918
TI  - 3T3-L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome
      proliferator-activated receptor-gamma-dependent and mediated by the caspase-3
      dependent apoptotic pathway.
AB  - Although thiazolidinediones (TZDs) are potent promoters of adipogenesis in the
      preadipocyte, they induce apoptosis in several other cell types, such as cancer
      cells, endothelial cells and T-lymphocytes. In this study, we investigated the
      proapoptotic effect of TZDs in mature 3T3-L1 adipocytes, which express high
      levels of the peroxisome proliferator-activated receptor-gamma (PPARgamma)
      protein. Apoptosis was induced in mature 3T3-L1 adipocytes by treatment with
      troglitazone, pioglitazone or prostaglandin J2, and could be blocked by the
      PPARgamma antagonist GW9662. Treatment with PPARgamma agonists also decreased Akt
      1 protein and phosphorylation levels without affecting phosphoinositide 3-kinase
      and PTEN. Further analysis indicated that in troglitazone-treated 3T3-L1
      adipocytes, Bad phosphorylation and Bcl-2 protein levels were reduced, and Bax
      translocation to the mitochondria was increased. Subsequently, cytochrome c
      release and caspase-3 cleavage were observed. TZD-induced adipocyte apoptosis
      could be blocked by the caspase-3 inhibitor Ac-DEVD-CHO or by overexpression of
      Bcl2. In cultured rat primary adipocytes, similar apoptosis-inducing effects of
      troglitazone were also observed. Thus, TZDs promote apoptosis in adipocytes
      through a PPARgamma-dependent pathway. This apoptosis is mediated by the
      inhibition of Akt-1, which decreases Bad phosphorylation and activates the
      mitochondrial apoptotic pathway.

PMID- 20050919
TI  - RMI1 deficiency in mice protects from diet and genetic-induced obesity.
AB  - The aim of this study is to discover and characterize novel energy homeostasis
      related molecules. We screened stock mouse embryonic stem cells established using
      the exchangeable gene trap method, and examined the effects of deficiency of the
      target gene on diet and genetic-induced obesity. The mutant strain 0283, which
      has an insertion at the recQ-mediated genome instability 1 (RMI1) locus,
      possesses a number of striking features that allow it to resist metabolic
      abnormalities. Reduced RMI1 expression, lower fasting-blood glucose and a reduced
      body weight (normal diet) were observed in the mutant mice. When fed a high-fat
      diet, the mutant mice were resistant to obesity, and also showed improved glucose
      intolerance and reduced abdominal fat tissue mass and food intake. In addition,
      the mutants were also resistant to obesity induced by the lethal yellow agouti
      (A(y)) gene. Endogenous RMI1 genes were found to be up-regulated in the liver and
      adipose tissue of KK-A(y) mice. RMI1 is a component of the Bloom's syndrome gene
      helicase complex that maintains genome integrity and activates cell-cycle
      checkpoint machinery. Interestingly, diet-induced expression of E2F8 mRNA, which
      is an important cell cycle-related molecule, was suppressed in the mutant mice.
      These results suggest that the regulation of energy balance by RMI1 is
      attributable to the regulation of food intake and E2F8 expression in adipose
      tissue. Taken together, these findings demonstrate that RMI1 is a novel molecule
      that regulates energy homeostasis.

PMID- 20050920
TI  - Erythrochelin--a hydroxamate-type siderophore predicted from the genome of
      Saccharopolyspora erythraea.
AB  - The class of nonribosomally assembled siderophores encompasses a multitude of
      structurally diverse natural products. The genome of the erythromycin-producing
      strain Saccharopolyspora erythraea contains 25 secondary metabolite gene clusters
      that are mostly considered to be orphan, including two that are responsible for
      siderophore assembly. In the present study, we report the isolation and
      structural elucidation of the hydroxamate-type tetrapeptide siderophore
      erythrochelin, the first nonribosomal peptide synthetase-derived natural product
      of S. erythraea. In an attempt to substitute the traditional activity assay
      guided isolation of novel secondary metabolites, we have employed a dedicated
      radio-LC-MS methodology to identify nonribosomal peptides of cryptic gene
      clusters in the industrially relevant strain. This methodology was based on
      transcriptome data and adenylation domain specificity prediction and resulted in
      the detection of a radiolabeled ornithine-inheriting hydroxamate-type
      siderophore. The improvement of siderophore production enabled the elucidation of
      the overall structure via NMR and MS(n) analysis and hydrolysate-derivatization
      for the determination of the amino acid configuration. The sequence of the
      tetrapeptide siderophore erythrochelin was determined to be D-alpha-N-acetyl
      delta-N-acetyl-delta-N-hydroxyornithine-D-serine-cyclo(L-delta-N-hydroxyornithine
      L-delta-N-acetyl-delta-N-hydroxyornithine). The results derived from the
      structural and functional characterization of erythrochelin enabled the proposal
      of a biosynthetic pathway. In this model, the tetrapeptide is assembled by the
      nonribosomal peptide synthetase EtcD, involving unusual initiation- and
      cyclorelease-mechanisms.

PMID- 20050921
TI  - Accessibility changes within diphtheria toxin T domain when in the functional
      molten globule state, as determined using hydrogen/deuterium exchange
      measurements.
AB  - The translocation domain (T domain) of diphtheria toxin adopts a partially folded
      state, the so-called molten globule state, to become functional at acidic pH. We
      compared, using hydrogen/deuterium exchange experiments associated with MS, the
      structures of the T domain in its soluble folded state at neutral pH and in its
      functional molten globule state at acidic pH. In the native state, the alpha
      helices TH5 and TH8 are identified as the core of the domain. Based on the high
      resolution structure of the T domain, we propose that TH8 is highly protected
      because it is buried within the native structure. According to the same
      structure, TH5 is partly accessible at the surface of the T domain. We propose
      that its high protection is caused by the formation of dimers. Within the molten
      globule state, high protection is still observed within the helical hairpin TH8
      TH9, which is responsible for the insertion of the T domain into the membrane. In
      the absence of the lipid bilayer, this hydrophobic part of the domain self
      assembles, leading to the formation of oligomers. Overall, hydrogen/deuterium
      exchange measurements allow the analysis of interaction contacts within small
      oligomers made of partially folded proteins. Such information, together with
      crystal structure data, are particularly valuable for using to analyze the self
      assembly of proteins.

PMID- 20050922
TI  - Nucleolin/C23 mediates the antiapoptotic effect of heat shock protein 70 during
      oxidative stress.
AB  - Although heat shock protein 70 (Hsp70) has been shown to markedly inhibit
      H(2)O(2)-induced apoptosis in C2C12 cells, and nucleolin/C23 has also been
      implicated in apoptosis, the relationship of these two molecules is still largely
      unknown. The aim of the current study was to investigate the potential
      involvement of nucleolin/C23 in the antiapoptotic mechanism of Hsp70. We found
      that primary cultures of neonatal rat cardiomyocytes underwent apoptosis upon
      H(2)O(2) treatment, and in these cells nucleolin/C23 protein was highly unstable
      and had a half-life of less than 4 h. However, transfection with Hsp70 greatly
      stabilized nucleolin/C23 and also protected the cells from H(2)O(2)-induced
      apoptosis. When nucleolin/C23 was knocked down with an antisense oligomer,
      H(2)O(2)-induced apoptosis became more severe, even in Hsp70-overexpressed cells,
      demonstrating an essential role of nucleolin/C23 in the antiapoptotic effects of
      Hsp70. Similar results were obtained by both nuclear morphology observation and
      caspase-3 activity assay. Therefore, these data provide evidence that
      nucleolin/C23 is an essential downstream effecter of Hsp70 in the protection of
      cardiomyocytes against oxidative stress-induced apoptosis.

PMID- 20050923
TI  - Roles of AP-2 transcription factors in the regulation of cartilage and skeletal
      development.
AB  - During embryogenesis, most of the mammalian skeletal system is preformed as
      cartilaginous structures that ossify later. The different stages of cartilage and
      skeletal development are well described, and several molecular factors are known
      to influence the events of this enchondral ossification, especially transcription
      factors. Members of the AP-2 family of transcription factors play important roles
      in several cellular processes, such as apoptosis, migration and differentiation.
      Studies with knockout mice demonstrate that a main function of AP-2s is the
      suppression of terminal differentiation during embryonic development.
      Additionally, the specific role of these molecules as regulators during
      chondrogenesis has been characterized. This review gives an overview of AP-2s,
      and discusses the recent findings on the AP-2 family, in particular AP-2alpha, AP
      2beta, and AP-2epsilon, as regulators of cartilage and skeletal development.

PMID- 20050924
TI  - Family-based studies indicate association of Engrailed 2 gene with autism in an
      Indian population.
AB  - Engrailed 2 (EN2) is a homeobox transcription factor involved in the patterning
      of cerebellum during brain development. Linkage analysis and studies on knockout
      mice support EN2, located on chromosome 7q36.3, as a potential risk locus for
      autism. Candidate gene approach also suggested association of EN2 with autism
      spectrum disorder (ASD) in various populations. Here, we have investigated the
      association of five markers [rs3735653 (C/T) in exon 1; rs34808376 (GC/-) and
      rs6150410 (CGCATCCCC/-) in promoter region; rs1861972 (A/G) and rs1861973 (C/T)
      in the intron] of the gene with autism and ASD in Indian population using family
      based approach. Probands have been recruited using Diagnostic and Statistical
      Manual of Mental Disorders Fourth Edition (DSM-IV) diagnostic criteria. Genotypic
      distributions conform to Hardy-Weinberg equilibrium. Genotyping analysis showed
      that the intronic single nucleotide polymorphisms (SNPs) are in complete linkage
      disequilibrium showing A-C and corresponding G-T allelic association. We observed
      significant preferential transmission of C allele of rs1861973 from the parents
      to affected offspring [transmission disequilibrium test (TDT): narrow diagnosis
      likelihood ratio statistics (LRS) = 6.63, P = 0.006; broad diagnosis LRS = 4.47,
      P = 0.05]. Interestingly, gender-based investigations showed significant
      transmission of C allele to the affected females [TDT: LRS = 7.36, P = 0.0025;
      haplotype-based haplotype relative risk (HHRR): LRS = 7.16, P = 0.02]. A maternal
      overtransmission for these alleles was also noted (TDT: LRS = 3.65, P = 0.036;
      HHRR: LRS = 2.81, P = 0.036). Bioinformatic analysis using TFSearch showed
      generation of Sp1 binding site in the presence of C allele. While Del-T haplotype
      formed from rs34808376-rs1861973 markers showed increased non-transmission, the
      Ins-C showed significant transmission suggesting protective effect and risk,
      respectively, conferred by these haplotypes in autism etiology. These results
      suggest positive genetic correlation of EN2 with autism in the Indian population.

PMID- 20050925
TI  - Mice lacking synapsin III show abnormalities in explicit memory and conditioned
      fear.
AB  - Synapsin III is a neuron-specific phosphoprotein that plays an important role in
      synaptic transmission and neural development. While synapsin III is abundant in
      embryonic brain, expression of the protein in adults is reduced and limited
      primarily to the hippocampus, olfactory bulb and cerebral cortex. Given the
      specificity of synapsin III to these brain areas and because it plays a role in
      neurogenesis in the dentate gyrus, we investigated whether it may affect learning
      and memory processes in mice. To address this point, synapsin III knockout mice
      were examined in a general behavioral screen, several tests to assess learning
      and memory function, and conditioned fear. Mutant animals displayed no anomalies
      in sensory and motor function or in anxiety- and depressive-like behaviors.
      Although mutants showed minor alterations in the Morris water maze, they were
      deficient in object recognition 24 h and 10 days after training and in social
      transmission of food preference at 20 min and 24 h. In addition, mutants
      displayed abnormal responses in contextual and cued fear conditioning when tested
      1 or 24 h after conditioning. The synapsin III knockout mice also showed aberrant
      responses in fear-potentiated startle. As synapsin III protein is decreased in
      schizophrenic brain and because the mutant mice do not harbor obvious anatomical
      deficits or neurological disorders, these mutants may represent a unique
      neurodevelopmental model for dissecting the molecular pathways that are related
      to certain aspects of schizophrenia and related disorders.

PMID- 20050926
TI  - Genetic influences on 'environmental' factors.
AB  - Childhood environment, social environment and behavior, leisure time activities
      and life events have been hypothesized to contribute to individual differences in
      cognitive abilities and physical and emotional well-being. These factors are
      often labeled 'environmental', suggesting they shape but not reflect individual
      differences in behavior. The aim of this study is to test the hypothesis that
      these factors are not randomly distributed across the population but reflect
      heritable individual differences. Self-report data on Childhood Environment,
      Social Environment and Behavior, Leisure Time Activities and Life Events were
      obtained from 560 adult twins and siblings (mean age 47.11 years). Results
      clearly show considerable genetic influences on these factors with mean broad
      heritability of 0.49 (0.00-0.87). This suggests that what we think of as measures
      of 'environment' are better described as external factors that might be partly
      under genetic control. Understanding causes of individual differences in external
      factors may aid in clarifying the intricate nature between genetic and
      environmental influences on complex traits.

PMID- 20050927
TI  - Thrombin generation and fibrinolysis in anti-factor IX treated blood and plasma
      spiked with factor VIII inhibitor bypassing activity or recombinant factor VIIa.
AB  - Activated prothrombin complex concentrates (aPCC) and recombinant activated
      factor VIIa (rFVIIa) are two important therapies in haemophilia patients with
      inhibitors and improve clot stability. We hypothesized that potential differences
      in procoagulant and fibrinolytic actions of aPCC and rFVIIa may lie in the clot
      stability against fibrinolytic activation. We used thrombin generation,
      fluorescence detection and thromboelastometry in anti-factor IXa (FIXa) aptamer
      treated whole blood (WB) and plasma to evaluate: (i) generation of thrombin and
      activated factor X (FXa) and (ii) viscoelastic properties of blood clots in the
      presence of tissue plasminogen activator (tPA) after addition of aPCC (0.4 U mL(
      1)) or rFVIIa (60 nm). Peak thrombin generation increased from 85 +/- 19 nm in
      aptamer-treated plasma to 276 +/- 83 nm and 119 +/- 22 nm after addition of aPCC
      and rFVIIa respectively (P < 0.001). FXa activity increased within 20 min by 87
      +/- 6% and by 660 +/- 97% after addition of aPCC and rFVIIa respectively (P <
      0.001). TPA-induced lysis time increased from 458 +/- 378 s in aptamer-treated WB
      to 1597 +/- 366 s (P = 0.001) and 1132 +/- 214 s (P = 0.075), after addition of
      aPCC and rFVIIa respectively. In this haemophilia model using the anti-FIXa
      aptamer, the larger amount of thrombin was generated with aPCC compared with
      rFVIIa, while FXa generation was more rapidly increased in the presence of
      rFVIIa. Furthermore, clot formation in anti-FIXa aptamer-treated WB was less
      susceptible to tPA-induced fibrinolysis after adding aPCC compared with rFVIIa.

PMID- 20050928
TI  - Interlocus non-random association of multiallelic polymorphisms spanning the
      coagulation factor VIII gene on human chromosome distalmost Xq28.
AB  - The most common severe hereditary bleeding disorder phenotype in humans, the
      coagulation factor VIII (F8) deficiency haemophilia A (HEMA), maps on Xq28 band,
      a region that comprises 11.7% of genes and 14.2% of phenotypes on X chromosome.
      Information about the distribution and extent of gametic disequilibrium (GD)
      covering the F8 gene is scarce, despite its relevance for linkage and association
      studies. The aim of this study was to determine the patterns, by frequency and
      strength, of non-random multiallelic interallelic associations between two-locus
      combinations of seven microsatellite loci (REN90833, F8Int25.2, F8Int22,
      F8Int13.2, HEMA154311.3, TMLHEInt5 and HEMA154507.3, in that physical order)
      spanning 0.813 Mb on distalmost Xq28. We measured sign-based interallelic D'
      coefficients in 106 men and in 100 women drawn from a single unrelated Brazilian
      population. Significance and patterns of GD using haploid and phased diploid
      sample probabilities were close to conformity. Only 9.18% of the variance of D'
      could be accounted for by changes in length, indicating that GD is not a
      monotonically decreasing function of length. We defined two regions of
      overlapping long-range GD extending 698 735 base pairs (bp) (REN90833/TMLHEInt5
      block) and 689 900 bp (F8Int13.2/HEMA154507.3 block) The extent of GD overlap is
      575 637 bp (F8Int13.2/TMLHEInt5 interstice). Extended haplotype homozygosity
      analysis centred at the F8 intronic loci revealed that the most frequent core
      haplotypes decay the least in the flanking GD. The F8 intronic loci attend
      distinct non-random association forces; F8Int13.2 serves at maintenance of the
      long-range overlapping pattern of GD, whereas F8Int25.2 and F8Int22 serve at
      lessening it in force or effect.

PMID- 20050929
TI  - Long-term evaluation of chromosomal breakages after radioisotope synovectomy for
      treatment of target joints in patients with haemophilia.
AB  - Radioisotope synovectomy (RS) is defined as the intra-articular injection of
      radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the
      target joint. The aim of this study was to investigate genotoxic effects on
      lymphocytes and malign transformation induced by Yttrium(90) (Y(90)) and
      Rhenium(186) (Re(186)) in children with haemophilia undergone RS. Forty
      haemophilia patients were enrolled. The mean age was 16.4 +/- 6.2 years (range: 8
      40). Y(90) was used for knees, Re(186) was used for other joints. For safety,
      cytogenetic analysis was performed to determine potential chromosomal changes
      after RS procedure at three different time points as prior to procedure, 3rd day
      and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was
      used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%)
      prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs
      prior to RS after 3 days of radioisotope exposure. At that time, the patients who
      had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The
      mean frequency of CBs slightly but not significantly increased in the 3rd day.
      However, there was a significant decreasing trend between 3rd and 90th days.
      Radioisotope synovectomy with Y(90) and Re(186) does not seem to induce the
      genotoxic effects significantly on peripheral blood lymphocytes. However, CBs
      even after one year in the re-evaluation of four patients, significant decrease
      in the number of CBs between the 3rd and 90th days and de novo CBs after exposure
      may be accepted as warning signals for young population. It should also be
      pointed out that families and patients be informed properly related with
      historical and potential dangers of radioisotopic agents.

PMID- 20050930
TI  - Maintenance of treatment logs by haemophilia patients.

PMID- 20050931
TI  - Falling into the coverage gap: Part D drug costs and adherence for Medicare
      Advantage prescription drug plan beneficiaries with diabetes.
AB  - OBJECTIVE: To compare drug costs and adherence among Medicare beneficiaries with
      the standard Part D coverage gap versus supplemental gap coverage in 2006. DATA
      SOURCES: Pharmacy data from Medicare Advantage Prescription Drug (MAPD) plans.
      STUDY DESIGN: Parallel analyses comparing beneficiaries aged 65+ with diabetes in
      an integrated MAPD with a gap versus no gap (n=28,780); and in a network-model
      MAPD with a gap versus generic-only coverage during the gap (n=14,984). PRINCIPAL
      FINDINGS: Drug spending was 3 percent (95 percent confidence interval [CI]: 1-4
      percent) and 4 percent (CI: 1-6 percent) lower among beneficiaries with a gap
      versus full or generic-only gap coverage, respectively. Out-of-pocket
      expenditures were 189 percent higher (CI: 185-193 percent) and adherence to three
      chronic drug classes was lower among those with a gap versus no gap (e.g., odds
      ratio=0.83, CI: 0.79-0.88, for oral diabetes drugs). Annual out-of-pocket
      spending was 14 percent higher (CI: 10-17 percent) for beneficiaries with a gap
      versus generic-only gap coverage, but levels of adherence were similar.
      CONCLUSIONS: Among Medicare beneficiaries with diabetes, having the Part D
      coverage gap resulted in lower total drug costs, but higher out-of-pocket
      spending and worse adherence compared with having no gap. Having generic-only
      coverage during the gap appeared to confer limited benefits compared with having
      no gap coverage.

PMID- 20050932
TI  - Managing care? Medicare managed care and patient use of cardiologists.
AB  - OBJECTIVE: To examine the impact of Medicare managed care (MMC) versus Medicare
      fee for service (MFFS) on stent patients' use of physicians with lower resource
      use and better outcomes. DATA SOURCES/STUDY SETTING: Retrospective secondary data
      from 2003 through 2006 for 67,476 patients without acute myocardial infarction,
      staying 2 or more days in hospital, and treated by 486 physicians in Florida
      performing 10 or more cases per quarter. STUDY DESIGN: Analysis was at the
      patient level. Multivariate logistic models estimated the probability of an MMC
      patient using a physician with a particular risk-adjusted profile rank with
      respect to hospital peers. PRINCIPAL FINDINGS: No differences were found in usage
      of physicians with shorter admissions. Compared with MFFS, MMC patients were
      significantly less likely to use physicians whose average mortality was the
      lowest/lowest quartiles/below median among facility peers, and more likely to use
      a physician ranked below median on live discharges directly home (not needing
      home health care, skilled nursing care, or a subacute hospital convalescence).
      Similar results were found with emergency admissions, and where physicians both
      attended and treated. CONCLUSIONS: Florida percutaneous coronary interventions
      patients insured by MMC used physicians with worse outcome profiles than those of
      MFFS patients. Results were not consistent with hospital care differences,
      physician-patient, or payor-physician selection, but they were consistent with
      selection of unobservably sicker members into MMC and concentration of MMC among
      physicians.

PMID- 20050933
TI  - Identification of hospital catchment areas using clustering: an example from the
      NHS.
AB  - OBJECTIVE: To develop a method of hospital market area identification using
      multivariate data, and compare it with existing standard methods. DATA SOURCES:
      Hospital Episode Statistics, a secondary dataset of admissions data from all
      hospitals in England, between April 2005 and March 2006. STUDY DESIGN: Seven
      criteria for catchment area definition were proposed. K-means clustering was used
      on several variables describing the relationship between hospitals and local
      authority districts (LADs) to enable the placement of every LAD into or out of
      the catchment area for every hospital. Principal component analysis confirmed the
      statistical robustness of the method, and the method was compared against
      existing methods using the seven criteria. PRINCIPAL FINDINGS: Existing methods
      for identifying catchment areas do not capture desirable properties of a hospital
      market area. Catchment areas identified using K-means clustering are superior to
      those identified using existing Marginal methods against these criteria and are
      also statistically robust. CONCLUSIONS: K-means clustering uses multivariate data
      on the relationship between hospitals and geographical units to define catchment
      areas that are both statistically robust and more informative than those obtained
      from existing methods.

PMID- 20050934
TI  - Comparison of health outcomes for male seniors in the Veterans Health
      Administration and Medicare Advantage plans.
AB  - OBJECTIVES: To compare the Veterans Health Administration (VHA) with the Medicare
      Advantage (MA) plans with regard to health outcomes. DATA SOURCES: The Medicare
      Health Outcome Survey, the 1999 Large Health Survey of Veteran Enrollees, and the
      Ambulatory Care Survey of Healthcare Experiences of Patients (Fiscal Years 2002
      and 2003). STUDY DESIGN: A retrospective study. EXTRACTION METHODS: Men 65+
      receiving care in MA (N=198,421) or in VHA (N=360,316). We compared the risk
      adjusted probability of being alive with the same or better physical (PCS) and
      mental (MCS) health at 2-years follow-up. We computed hazard ratio (HR) for 2
      year mortality. PRINCIPAL FINDINGS: Veterans had a higher adjusted probability of
      being alive with the same or better PCS compared with MA participants (VHA 69.2
      versus MA 63.6 percent, p<.001). VHA patients had a higher adjusted probability
      than MA patients of being alive with the same or better MCS (76.1 versus 69.6
      percent, p<.001). The HRs for mortality in the MA were higher than in the VHA
      (HR, 1.26 [95 percent CI 1.23-1.29]). CONCLUSIONS: Our findings indicate that the
      VHA has better patient outcomes than the private managed care plans in Medicare.
      The VHA's performance offers encouragement that the public sector can both
      finance and provide exemplary health care.

PMID- 20050935
TI  - Children's exposure to second-hand smoke in the home: a household survey in the
      North of England.
AB  - Exposure of children to second-hand smoke (SHS) leads to increased risk of health
      and social problems and uptake of smoking in the future. We aimed to assess the
      prevalence of children's exposure to SHS in their homes, in a deprived area in
      the North of England and identify what people thought would help them achieve a
      smoke-free home (SFH). We performed a cross-sectional survey of 318 households
      with at least one child aged under 16 years in Beeston Hill, a deprived locality
      in Leeds, England in June 2008. One hundred and seventy-three households [54%,
      95% confidence interval (C.I.) 49-60] had at least one smoker in the house. In
      42% (95% C.I. 35-50) of these households (n = 73), smoking took place in the
      presence of children. The odds of allowing smoking in front of children were 2.2
      (95% C.I. 1.1-4.5) times greater in households whose head had less than A-level
      (national exams at 18 years) or equivalent qualification than in homes with a
      more qualified head of household. 92% of respondents were aware that SHS has
      negative effects on children's health. However, 71% felt more information about
      health risks to children would help reduce exposure to SHS in the home. Smoking
      in the presence of children takes place in a relatively high proportion of
      households with smoker(s), despite media awareness campaigns regarding the
      dangers of passive smoking launched alongside the recently enforced smoke-free
      public and workplaces legislation. Specific promotion of SFHs is needed to
      protect the health of children.

PMID- 20050938
TI  - Sildenafil efficacy in erectile dysfunction secondary to spinal cord injury
      depends on the level of cord injuries.
AB  - To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile
      dysfunction (ED) secondary to upper motor neuron (UMN) and lower motor neuron
      (LMN) spinal cord injury (SCI). After taking consents 105 patients suffering from
      ED were enrolled in this prospective study. Seventy-two patients had signs and
      symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed (UMN and
      LMN) spinal cord injuries. The patients took 50-100 mg sildenafil or placebo
      tablet at least 45 min before sexual intercourse. Based on a IIEF questionnaire,
      success in achieving erection adequate for sexual intercourse was compared
      between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries. In
      patients with UMN disease, sildenafil was effective in 82% of patients and its
      efficacy was statistically higher than placebo (82 vs. 25%, p < 0.05). Twenty
      eight per cent of patients with non-UMN disease had a favourable response to
      sildenafil that was not statistically different from placebo. Sildenafil seems
      more effective in the treatment of neurogenic ED secondary to UMN spinal cord
      injury compared with that secondary to LMN injury. Actually, its efficacy on LMN
      injuries does not seem different from placebo and administration of this
      treatment may not be effective in spinal cord injury which has caused LMN
      symptoms.

PMID- 20050937
TI  - Opportunistic infections and organ-specific diseases in HIV-1-infected children:
      a cohort study (1990-2006).
AB  - OBJECTIVES: Highly active antiretroviral therapy (HAART) has dramatically changed
      the natural history of HIV infection in children, but there are few studies in
      the literature about the incidence of clinical manifestations after HAART in this
      population, compared with adults. The aim of this study was to describe the
      influence of the widespread use of HAART on the development of opportunistic
      infections and organ-specific diseases in HIV-infected children. METHODS: An
      observational study of a cohort of 366 vertically HIV-infected children followed
      from 1990 to 2006 was carried out. According to the main antiretroviral protocol
      used, three calendar periods (CPs) were defined and compared: CP1 (1990-1996: no
      patients on HAART), CP2 (1997-1999: <60% on HAART) and CP3 (2000-2006: >60% on
      HAART). RESULTS: Children experienced a progressive increase in CD4 T cell count
      (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly,
      rates of death, AIDS, opportunistic infections (bacteraemia, candidosis,
      cryptosporidiosis and bacterial pneumonia) and organ-specific diseases (wasting
      syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and
      HIV-associated encephalopathy) were lower in CP2 and CP3 than in CP1.
      CONCLUSIONS: This study provides evidence of improved clinical outcomes in HIV
      infected children over time and shows that mortality, AIDS, opportunistic
      infections and organ-specific diseases declined as HAART was progressively
      instituted in this population.

PMID- 20050936
TI  - Is long-term virological response related to CCR5 Delta32 deletion in HIV-1
      infected patients started on highly active antiretroviral therapy?
AB  - OBJECTIVE: The aim of the study was to determine whether the chemokine (C-C
      motif) receptor 5 (CCR5) Delta32 deletion is associated with long-term response
      to combination antiretroviral treatment (cART) in HIV-1-infected patients.
      METHODS: The genetic substudy of the Agence Nationale de Recherche sur le SIDA
      (ANRS) CO8 APROCO-COPILOTE cohort included 609 patients who started protease
      inhibitor-containing cART in 1997-1999. Patients were considered to have a
      sustained virological response if all plasma HIV RNA measurements in the period
      considered were <500 HIV-1 RNA copies/ml, allowing for a single blip. Virological
      response was compared between patients heterozygous for CCR5 Delta32 (Delta32/wt)
      and wild-type patients (wt/wt) from month 4 to year 3 and from month 4 to year 5.
      Logistic regression analysis was used to adjust for baseline demographical data,
      HIV RNA, CD4 cell count, antiretroviral exposure status, time spent on
      antiretroviral therapy at years 3 and 5 and adherence to treatment (month 4 to
      year 3 or 5). RESULTS: A sustained virological response was more frequent in
      Delta32/wt than in wt/wt patients from month 4 to year 3, with 66%vs. 52% of
      patients, respectively, showing a sustained response (P=0.02); after adjustment
      for potential confounders, the association of Delta32 with a sustained response
      was nearly significant (P=0.07). A sustained virological response was also more
      frequent in Delta32/wt patients up to year 5, with 48% showing a sustained
      response vs. 35% of wt/wt patients (P=0.01); after adjustment, Delta32 remained
      significantly associated with a sustained virological response up to year 5
      (P=0.04). There was no association with CD4 response. CONCLUSION: The Delta32
      deletion in Delta32/wt patients is associated with a beneficial virological
      response to cART in the long term. Whether this association is a direct effect of
      the Delta32 deletion remains unclear and requires confirmation in further
      observational studies.

PMID- 20050939
TI  - Arrangement of PMCA4 in bovine sperm membrane fractions.
AB  - The plasma membrane Ca(2+) -ATPase (PMCA) is the main restorer of Ca(2+) balance
      in sperm. Particularly, PMCA isoform 4 has an essential function in sperm
      fertility by its participation in gaining sperm hypermotility. PMCA activity is
      influenced by its lipid environment. Sperm membranes exhibit lipid raft
      microdomains or detergent-resistant membrane domains, enriched in sphingolipids
      and cholesterol, forming functional specialized areas. Lipid and protein
      composition of lipid rafts alters during the capacitation process, which is
      characterized by a cholesterol efflux. In this study, the localization of PMCA4
      in lipid membrane fractions of the sperm plasma membrane was investigated. We
      identified PMCA4 in both the detergent-resistant membrane (DRM) and in the
      detergent-soluble (DS) fraction of caput and cauda sperm, respectively.
      Capacitation did not influence PMCA4 localization. In immunocytochemical studies
      PMCA4 was co-localized with the lipid raft/DRM marker caveolin in the mid piece
      of caput and cauda sperm. Functional studies with seminal vesicle major protein
      PDC-109 showed that the Ca(2+) -ATPase activity in DS fractions of cauda sperm
      and capacitated cauda sperm was stronger enhanced than in the DRMs. In both
      fractions the effect was statistically significant. In contrast, in lipid overlay
      experiments PDC-109 interacted stronger with the lipids extracted from DRMs than
      with lipids extracted from DS. Our results indicate a possible functional
      compartmentalization of PMCA in bull sperm membranes and point to a presumptive,
      yet unknown interaction partner of Ca(2+) -ATPase and PDC-109, mediating the PDC
      109 action from DRMs to the DS fraction of sperm plasma membrane.

PMID- 20050940
TI  - Relationship between symptoms of androgen deficiency and psychological factors
      and quality of life among Chinese men.
AB  - Androgen deficiency in the ageing male (ADAM) was proposed to characterize a
      symptom cluster of decrease in sexual function and strength, dysphoria and
      osteopenia in ageing men with decreased levels of androgens. Unlike menopause,
      literature on the topic is scarce and focuses mainly on the physiological aspects
      of the problem. However, men with ADAM also face a milieu of psychosocial
      stressors which may adversely affect their mental health. It is pertinent to
      examine ADAM within a psychological context. This study aims to determine the
      prevalence of symptoms of ADAM among Chinese men, and to examine their
      relationship with psychological distress and quality of life. A cross-sectional
      design was employed with standardized questionnaires to assess symptoms of ADAM
      and related psychological factors. The ADAM questionnaire, Hospital Anxiety and
      Depression Scale, Perceived Stress Scale, General Health Questionnaire and Short
      Form Health Survey-12 were administered to a community sample of 311 Chinese men
      (aged 40-80) attending a family medicine clinic in Hong Kong. Demographic
      information was also collected. A total of 87.8% of the sample was screened ADAM
      positive using the ADAM questionnaire. Age, duration of marriage, occupation,
      household income and physical health were found to be significantly associated
      with ADAM status. ADAM positive individuals were found to have higher anxiety and
      depression scores, higher stress level, higher psychiatric morbidity and poorer
      physical and mental quality of life compared with their ADAM negative
      counterparts. Symptoms of ADAM are prevalent among the Chinese. ADAM positivity
      as measured by the ADAM questionnaire is associated with poorer psychological
      well-being and quality of life in the ageing population. Further research and
      clinical attention to the psychological needs of this population is warranted.

PMID- 20050941
TI  - Endocrine disruptors targeting ERbeta function.
AB  - Endocrine disruptive chemicals (EDCs) circulating in the environment constitute a
      risk to ecosystems, wildlife and human health. Oestrogen receptor (ER) alpha and
      beta are targeted by various kinds of EDCs but the molecular mechanisms and long
      term consequences of exposure are largely unknown. Some biological effects of
      EDCs are mediated by the aryl hydrocarbon receptor (AhR), which is a key player
      in the cellular defence against xenobiotic substances. Adding complexity to the
      picture, there is also accumulating evidence that AhR-ER pathways have an
      intricate interplay at multiple levels. In this review, we discuss some EDCs that
      affect the oestrogen pathway by targeting ERbeta. Furthermore, we describe some
      effects of AhR activities on the oestrogen system. Mechanisms as well as
      potential adverse effects on human health are discussed.

PMID- 20050942
TI  - Relating juvenile spatial distribution to breeding patterns in anadromous
      salmonid populations.
AB  - 1. Spatial within-population heterogeneity in density probably affects
      competition intensity and may have a fundamental role in shaping population
      dynamics and carrying capacity. This may be particularly relevant for organisms
      where limitations on juvenile mobility cause maternal choice of breeding
      locations to influence the spatial distribution of younger life stages. 2. In
      this study, we mapped redd locations and the resulting densities of juveniles the
      following year along the entire reach (9.2 km) of a river holding natural
      populations of anadromous salmonids (Atlantic salmon and brown trout). These data
      were used to quantify the spatial scale over which breeding influences juvenile
      densities, and hence becomes important for density-dependent processes. 3.
      Although the observed cumulative distributions indicated a relatively uniform
      distribution of breeding along the river, autocorrelation analyses identified
      spatial patchiness of both breeding and resulting juveniles on a local scale.
      Furthermore, cross-correlations suggested a close spatial relationship between
      distribution of redds and juveniles. 4. Using spatially explicit hockey-stick
      stock-recruitment functions, we found juvenile salmonid density to be mostly
      influenced by the amount of breeding upstream of a given location. This influence
      decreased rapidly within the first 75-150 m. Thus, female choice with regard to
      breeding location gave rise to a heterogeneous distribution of offspring on a
      spatial scale of almost two orders of magnitude finer than that of the whole
      population (9.2 km). 5. The results are consistent with smaller scale
      experimental studies of salmonids, and emphasize the role for maternal choice of
      breeding locations in causing substantial spatial heterogeneity in juvenile
      densities within natural populations. Due to effects of density heterogeneity on
      overall levels of competition, this adds another layer of complexity to the
      dynamics of salmonid populations even in populations where breeding appears to be
      relatively uniformly distributed through space, and potentially also for a range
      of other organisms where juvenile dispersal is constrained.

PMID- 20050943
TI  - Effects of dietary glucose inclusion on reproductive performance, milk
      compositions and blood profiles in lactating sows.
AB  - Twenty-four multiparous sows were used to investigate the effects of dietary
      glucose inclusion on reproductive performance, milk compositions, blood
      metabolites and hormones during lactation. The sows were randomly assigned to
      four treatments and each treatment had six replicates (sows). The diets were
      added with 0%, 1%, 3% or 5% glucose at the expense of corn and fed to sows for 24
      days. The loss of backfat thickness during lactation was quadratically decreased
      (p = 0.008) and the wean-to-oestrus interval was shortened (linear, p = 0.013;
      quadratic, p = 0.009) with increasing levels of dietary glucose supplementation.
      The reproductive performance was not affected (p > 0.05) by different dietary
      glucose contents. Increased concentrations of total solid and fat in milk were
      noted (p < 0.05), whereas there was no difference on colostrum compositions. With
      increasing levels of dietary glucose inclusion, the concentrations of blood urea
      nitrogen (p = 0.004) and glucose (p = 0.029) were linearly increased at weaning.
      The concentrations of insulin were increased at post-farrowing (linear, p =
      0.027; quadratic p = 0.013) and weaning (linear, p = 0.029; quadratic, p =
      0.017), respectively. Furthermore, the pulses of insulin and FSH at weaning were
      linearly (p = 0.049) and quadratically (p = 0.015) increased with the increasing
      levels of dietary glucose inclusion. In conclusion, this study indicated that
      inclusion of 3% glucose in lactating diet could reduce backfat loss, increase
      milk fat and have no negative effect on reproductive performance in multiparous
      sows.

PMID- 20050945
TI  - Digestibility and nitrogen utilization in sheep fed enset (Ensete ventricosum)
      pseudostem or corm and graded levels of Desmodium intortum hay to wheat straw
      based diets.
AB  - The aim of this study was to investigate the effects of different levels of
      Desmodium intortum (Desmodium) hay supplementation in sheep fed fixed amounts of
      enset pseudostem or corm and a basal diet of wheat straw on intake, digestibility
      and nitrogen utilization. Eighteen male sheep with a mean (+/- SD) live weight of
      20.5 +/- 1.45 kg were assigned to six treatments in a completely randomized
      design and fed either 108 g dry matter (DM) enset pseudostem or 165 g DM enset
      corm each with three levels (100, 200 and 300 g) of hay supplementation. For the
      pseudostem diets, there was no significant difference in total DM intake. Total
      crude protein (CP) intake and N retention increased with increasing levels of hay
      in both pseudostem and corm diets. The apparent digestibility of DM, OM, CP, acid
      detergent fibre and neutral detergent fibre (NDF) and microbial nitrogen supply
      (MN) at 100 g was lower that other levels of supplementation. For the corm diets,
      total DM and OM intake and MN supply increased with increasing levels of hay. The
      digestibility decreased (p < 0.001) with increasing levels of supplementation.
      The results suggest that at least 300 g (395 g/kg dietary DM) of Desmodium hay is
      required in pseudostem diets, whereas 200 g (337 g/kg dietary DM) may be
      sufficient in corm diets for efficient nutrient utilization.

PMID- 20050944
TI  - Luteinizing hormone and growth hormone secretion in early lactating Spanish beef
      cows.
AB  - The episodic release of luteinizing hormone (LH) and growth hormones (GH) was
      studied in three suckling regimens and two breeds of Spanish suckled cows. Parda
      de Montana (PA) cows (n = 21) were assigned to once-daily, twice-daily or ad
      libitum (ADLIB) suckling. Pirenaica (PI) cows (n = 7) were used to evaluate the
      breed effect in twice-daily suckling. Coccygeal blood samples were collected
      twice weekly during lactation to determine the interval from calving to first
      ovulation through peripheral progesterone. On day 32 +/- 3 post-partum, jugular
      blood samples were drawn at 15 min intervals during 8 h to analyse circulating LH
      and GH. The interval to first ovulation was greater in PA cows suckling ADLIB
      than in restricted suckling treatment (RESTR1), whereas in RESTR2 it did not
      differ from the other two treatments. There were no differences between PA and PI
      cows in the interval to first ovulation. RESTR1 cows showed a tendency to have
      shorter LH peak widths than ADLIB cows. PA cows showed a tendency to have longer
      LH peak widths than their PI counterparts. There were no differences across
      treatments or breeds in any of the GH measures of secretion. The LH release was
      more affected by breed than by suckling frequency, whereas that of GH was not
      influenced by any of these parameters. The variables that best allowed
      discrimination between ADLIB and restricted nursing systems were the interval to
      post-partum first ovulation, LH peak number and the mean GH concentration.

PMID- 20050946
TI  - Influence of dietary fat source and supplementary alpha-tocopheryl acetate on
      pulmonary hypertension and lipid peroxidation in broilers.
AB  - An experiment was conducted to examine pulmonary hypertension and lipid
      peroxidation of broilers as affected by dietary fat source and alpha-tocopheryl
      acetate. Two hundred and forty day-old male chicks were used in a completely
      randomized design with five treatments consisted of four replicates and 12 chicks
      per replicate. Treatments included a control group that received no supplemental
      fat (treatment 1) or groups that received diets supplemented with beef tallow,
      soybean oil, a 50:50 blend of beef tallow and soybean oil, or soybean oil plus
      alpha-tocopheryl acetate added at 220 mg/kg (treatments 2 to 5). All diets were
      kept isoenergetic and isonitrogenous and diet treatments 2 to 5 had 50 g/kg of
      fat supplement. Results showed that weight gain and feed consumption were
      significantly (p <= 0.05) increased by adding fat to the diet during the starter
      stage. However, birds that received fat-supplemented diets gained less (p <=
      0.05) during the grower period. Serum malone dialdehyde concentration and
      glutathione peroxidase activity were not affected by dietary treatments with the
      exception that inclusion of alpha-tocopheryl acetate to the diet supplemented
      with soybean oil significantly (p < 0.05) reduced the activity of the enzyme when
      measured at 21 days of age. The relative weights of heart and liver and the right
      ventricle weight to total ventricle weight ratio were greater in broilers fed fat
      supplemented diets (p < 0.05).

PMID- 20050947
TI  - Gelatinase activities and haptoglobin concentrations in healthy and in
      degenerative articular cartilage of pigs.
AB  - The objectives of this study were to investigate the activity of the matrix
      metalloproteinase (MMP)-2 and MMP-9 in healthy and in degenerative cartilage and
      to characterize the relation with the acute phase protein haptoglobin (HP) in
      articular cartilages of pigs. Joint surfaces of the proximal and distal humerus
      and femur of fattening pigs were histopathologically classified. In addition,
      cartilage homogenates and synovia were obtained. The tissue homogenates were
      analysed for gelatinase activity by zymography and by activity assay. The
      concentrations of HP in cartilage homogenates, in synovia and in serum were
      analysed by ELISA. High enzymatic activity of the MMP-2 latent form was observed
      in zymography in all samples. Zymographic activities of MMP-2 active form and MMP
      9 (active and latent form) were detected at low levels in some samples.
      Comparison of the zymographic activities of gelatinases in unaltered vs. altered
      cartilages yielded no differences. In contrast to zymography, cartilage
      homogenates were negative for MMP-2 and MMP-9 in the activity assays. The
      concentrations of HP in cartilage homogenates and in synovia from samples without
      alteration and from samples with massive alterations were not different. When
      classified according to their HP concentration, cartilage homogenates with
      increased HP concentrations had higher (p < 0.05) zymographic activities of the
      MMP-2 active form. For the two MMPs investigated, there was no detectable
      relationship with degenerative processes in the cartilage.

PMID- 20050948
TI  - Effect of different levels of mannan-oligosaccharide supplementation on the
      apparent ileal digestibility of nutrients, N-balance and growth performance of
      weaned piglets.
AB  - Several studies report that dietary mannan-oligosaccharides (MOSs) improve the
      growth performance of piglets, however, only a few studies focus on nutrient
      digestibility. The aim of the study was to investigate the effect of dietary MOS
      on ileal digestibility of nutrients and on N-balance and growth performance of
      piglets weaned at 28 days of age. Three experiments were conducted: a
      digestibility trial with a total of 30, simple T-cannulated piglets (Exp. 1), a N
      balance trial with a total of 48 intact piglets (Exp. 2) and a performance trial
      with a total of 324 piglets (Exp. 3). In Exp. 1 and 2, the same five dietary
      treatments were carried out by supplementing the basal diet with 0, 1, 2, 4 g MOS
      or with 0.2 g antibiotic growth promoter (AGP, Avilamycin) per kg of diet. In
      Exp. 3, three dietary treatments were used as follows: the basal diet was
      supplemented no additive, 2 g MOS or 0.2 g AGP (Avilamycin) per kg of diet.
      Dietary MOS (2 or 4 g/kg) enhanced the ileal digestibility of crude protein
      similar to antibiotics. Addition of 1 g/kg MOS significantly increased the
      digestibility of Ca and P by 8.4% and 7.7% units, respectively; however, further
      increment did not enhance the absorption. Addition of 1 or 2 g/kg MOS
      significantly increased the ileal digestibility of lysine, methionine, cystine
      and threonine with the same magnitude or even more than the AGP. In our study,
      MOS supplementation had no influence on N-balance and growth parameters. Because
      of the better apparent ileal digestibility of certain nutrients, however, the
      protein, lysine, methionine, cystine, threonine, Ca and P contents of the diet
      can probably be reduced without weakening the rearing performance of piglets,
      when the diet is supplemented with 2 g/kg MOS.

PMID- 20050949
TI  - Monitoring of vitamin E status of dry, early and mid-late lactating organic dairy
      cows fed conserved roughages during the indoor period and factors influencing
      forage vitamin E levels.
AB  - Analysis of blood plasma of 60 cows selected on six Flemish organic dairy farms
      revealed that on average 12% of all samples and on one farm up to 28% of the
      organic cows showed plasma vitamin E concentrations less than 3.0 MUg/ml, which
      is considered the minimum level to avoid health risks due to vitamin E shortages.
      Furthermore, this study showed early lactating and dry cows to be more at risk in
      relation to animals in mid-late lactation. In European organic farming, vitamin
      supplements are only allowed if granted by the local authority to satisfy daily
      requirements. Therefore, the vitamin E content of the feedstuffs used on the
      farms was determined. Grass clover silage (GCS) and mixed silage had
      significantly more vitamin E than hay, maize or grain (p < 0.05) [mean (SD): 52
      (35), 29 (20), 4.5 (1.7), 4.9 (4.4) and 7.1 (3.8) mg/kg DM, respectively].
      Apparently, variation in the vitamin E content in the silage samples was huge.
      Hence, the vitamin E content of ryegrass, white and red clover was determined in
      a second lab scale experiment and the effects of wilting, DM content and
      supplementation of ensiling additives were investigated. Fresh ryegrass had a
      higher vitamin E content than white and red clover (p < 0.05) [156 (11.3), 49.3
      (0.67) and 74.3 (5.73) MUg/g DM, respectively]. These differences remained after
      the wilting or ensiling. Supplementation of formic acid or lactic acid bacteria
      at ensiling had no significant effect on the vitamin E content. Overall, it can
      be concluded that GCS is the most important source of vitamin E in organic dairy
      farming. A legal possibility for case-related supplementation should be retained
      in organic dairy farming as approximately 18% of all dry and early lactating cows
      were at risk of vitamin E shortage.

PMID- 20050950
TI  - Inulin-coated butyrate increases ileal MCT1 expression and affects mucosal
      morphology in the porcine ileum by reduced apoptosis.
AB  - Carbohydrates, which were not digested in the jejunum, will be fermented by micro
      organisms to short chain fatty acids. These are transported by the
      monocarboxylate transporter 1 (MCT1) through the gut wall and serve as fuels for
      colonic cells. To deliver butyrate to the distal part of the intestine, inulin
      with a low precaecal digestibility was chosen as a coating material.
      Approximately 150 g of inulin-coated butyrate (containing 81 g butyrate) per day
      was fed to pigs (mean weight: 97 kg) over a period of 6 days after an adaptation
      period of 6 days with linear increasing amounts of butyrate. The following
      observations compared to controls were observed: (1) coating was digested
      microbially in the ileum; (2) MCT1-mRNA showed a higher expression in the ileum;
      (3) apoptosis was reduced in the ileum but mitosis was not changed; and (4)
      length of villi increased by approximately 25% in the ileum. Feeding inulin
      coated butyrate resulted in an increased ileal surface. Delivery of butyrate to
      the colon requires a more resistant inulin-coating.

PMID- 20050951
TI  - Ruminal and total tract phosphorus release from feedstuffs in cattle measured
      using the mobile nylon bag technique.
AB  - Phosphorus (P) excretion in manure is a concern for dairy and beef producers.
      Excess P released into surface water runoff can lead to eutrophication and algal
      blooms in streams and lakes. One approach to reducing P excretion is to reduce
      dietary P. Data regarding P release from feedstuffs is limited and more precise
      formulations based on specific feed P release in the digestive tract may be one
      way to lower excreted P. In this experiment, the mobile nylon bag technique was
      used to determine the disappearance of P in corn silage, alfalfa hay, Coastal
      bermudagrass hay, and Tifton-85 bermudagrass hay in steers after ruminal (24 h),
      ruminal + pepsin/HCl (rumen + PHCl), and ruminal + pepsin/HCl + intestinal (rumen
      + PHCl + I) incubation. Ruminal disappearance of P differed (p < 0.05) between
      feedstuffs and by site of incubation. Total tract (rumen + PHCl + I) P
      disappearance for corn silage, alfalfa hay, Coastal bermudagrass hay, and Tifton
      85 bermudagrass hay were 90.6%, 93.7%, 83.8% and 84.0% respectively. The range in
      P release (approximately 7%) indicates that considering P availability when
      balancing rations could have a measurable impact on subsequent P excretion from
      ruminants. More data concerning P availability as affected by other feed
      ingredients or plant species, maturity, and/or quality are needed to more
      accurately define P release from ruminant feeds.

PMID- 20050952
TI  - Nitrogen and energy utilization in lactating dairy goats fed diets with different
      legume seeds.
AB  - The N and energy utilization of diets with different legume seeds was analysed in
      lactating goats. Four isonitrogenous and isoenergetic diets were used and in each
      case 30% of the protein was supplied by one of four different legume seeds:
      lupins (L), faba beans (FB), bitter vetch (BV) and vetch (V). A group of eight
      Granadina goats, allocated to a replicated 4 * 4 Latin Square, were used. The N
      and energy utilization of the different diets may be considered adequate; milk
      N/intake N was approximately 0.20, milk N/N balance was approximately 0.50 and
      milk energy/metabolizable energy was approximately 0.30. Under similar N and
      energy intakes, faecal and urinary excretion of N and the quantities in milk did
      not vary significantly. However, the partition of the N balance between milk
      production and deposit within the body varied depending on the diet. Although
      this N available to the metabolism was the highest for the FB diet, the quantity
      of this directed to milk was the lowest. Finally, the faecal and urinary
      excretion with respect to the quantity directed to milk production did not vary
      significantly among the different diets.

PMID- 20050953
TI  - Description of development of rumen ecosystem by PCR assay in milk-fed, weaned
      and finished lambs in an intensive fattening system.
AB  - This study examined the reticulo-rumen characteristics of the microbial community
      and its fermentative characteristics in milk-fed, at weaning and finished lambs
      in a conventional fattening system. Five lambs were assigned to each of three
      groups: milk-fed lambs slaughtered at 30 days (T30), weaned lambs slaughtered at
      45 days (T45) and 'finished lambs' slaughtered at 90 days (T90). At slaughter,
      rumen size, fermentation parameters (pH, volatile fatty acids and microbial
      enzyme activity) and protozoal counts were recorded. Quantitative PCR was used to
      quantify the genes encoding 16S and 18S ribosomal DNA of the rumen bacterial and
      protozoal populations, respectively, and the sequential colonization of the rumen
      by cellulolytic (Ruminococcus albus, Ruminococcus flavefaciens) and amylolytic
      (Prevotella ruminicola, Streptococcus bovis) bacteria, and protozoa (Entodinium
      sp.). Denaturing gradient gel electrophoresis was used to study the development
      of rumen microbiota biodiversity. Intake of solid food before weaning caused a
      significant increase in rumen weight (p < 0.0001) and bacterial DNA (p < 0.05)
      and volatile fatty acid analysis concentration (p < 0.01), whereas pH declined.
      In milk-fed lambs, cellulolytic bacteria were evident after 30 days. Thereafter,
      in the 45-day and 90-day groups, the proportions of R. flavefaciens decreased and
      R. albus increased. Amylolytic bacteria were present in milk-fed lambs; the
      proportion of P. ruminicola increased in fattening lambs and S. bovis was the
      least abundant species. Protozoal concentrations were irregular; milk-fed lambs
      had a significant number of protozoa species from Entodinium and subfamily
      Isotrichiidae, but they disappeared at weaning. Lamb rumen were refaunated in
      some individuals at 90 days (Entodinium and subfamily Diplodiniinae spp.),
      although individual concentrations were variable.

PMID- 20050954
TI  - Ileal endogenous amino acid flow of broiler chickens under high ambient
      temperature.
AB  - High environmental temperature has detrimental effects on the gastrointestinal
      tract of poultry. An experiment was conducted to determine the effect of acute
      heat stress on endogenous amino acid (EAA) flow in broiler chickens. A total of
      90, day-old broiler chicks were housed in battery cages in an environmentally
      controlled chamber. Chicks were fed a nitrogen-free diet on day 42 following
      either no heat exposure (no-heat) or 2 weeks exposure to 35 +/- 1  degrees C for
      3 h from days 28 to 42 (2-week heat) or 1 week exposure to 35 +/- 1  degrees C
      for 3 h from days 35 to 42 (1 week heat). The most abundant amino acid in the
      ileal flow was glutamic acid, followed by aspartic acid, serine and threonine in
      non-heat stressed group. The EAA flow in 1-week heat and 2-week heat birds were
      significantly (p < 0.05) higher than those under no heat exposure (14682, 11161
      and 9597 mg/kg of dry matter intake respectively). Moreover, the EAA flow of 2
      week heat group was less than 1-week heat group by approximately 36%. These
      observations suggest that the effect of heat stress on EAA flow is mostly
      quantitative; however, heat stress may also alter the content of EAA flow
      qualitatively.

PMID- 20050955
TI  - Intravenous injections of cobalt reduce fatty acid desaturation products in milk
      and blood of lactating cows.
AB  - The objective of this study was to determine whether intravenous infusion of Co
      affects levels of fatty acid desaturation products in bovine milk. Six cows were
      assigned to two replicated 3 * 3 Latin squares with 14-day periods. Treatment
      occurred on days 1 to 5 and depuration occurred on days 6-14. Two treatments were
      tested, the first consisting of per os supplementation of 3.5 g Co daily in the
      form of Co acetate and the second consisting of intravenous injection of 175 mg
      Co daily in the form of Co acetate diluted in saline solution. The third
      treatment was a control. Both Co treatments decreased cis-9 18:1 levels from
      approximately 18 to 14 g/100 g fatty acids, and increased 18:0 levels from 11 to
      17 g/100 g fatty acids in milk fat (p < 0.001). The proportions of cis-9 10:1,
      cis-9 12:1, cis-9 14:1, cis-9 16:1 and cis-9 17:1 decreased (p < 0.001), whereas
      17:0 and trans-11 18:1 increased (p < 0.001). In blood plasma, levels of cis
      (6,9,12) 18:3 (p < 0.001) and cis (8,11,14,17) 20:4 (p = 0.008) decreased after
      both the Co treatments. It is concluded that intravenous supply of Co reduces
      levels of fatty acid desaturation products in both bovine milk and blood.

PMID- 20050956
TI  - Increased colostral somatic cell counts reduce pre-weaning calf immunity, health
      and growth.
AB  - Our objective was to study the relationships between colostral somatic cell
      counts (SCC, a criterion for mastitis severity at parturition) and early calf
      growth, blood indicators of immunity, and pre-weaning faecal and health states.
      Sixty-nine Holstein cows were assigned to three groups of greater (n = 21, 5051 *
      10(3)), medium (n = 38, 2138 * 10(3)) and lower (n = 10, 960 * 10(3)) colostral
      SCC (per ml) in a completely randomized design. Calves received 2 l of colostrum
      on day 1, and jugular blood was sampled at birth, at 3 h after the first
      colostrum feeding and at 42 days of age for immunoglobulin G (IgG) measurements.
      Calves were fed transition milk from their dams until 3 days of age and whole
      milk from 4 to 60 days of age twice daily at 10% of body weight. Health status
      and faecal physical scores were recorded daily for 42 days. Increased colostral
      SCC was associated with increased serum IgG at parturition. Colostral pH
      increased and fat percentage decreased linearly with the rising SCC. Feeding
      colostrum with greater SCC was associated with reduced serum IgG concentrations
      at 3 h after first colostrum feeding, greater incidences of diarrhoea and
      compromised health status during the first 42 days of age, and reduced weaning
      weight gain, but had no effects on calf body length and withers height. Colostral
      volume and percentages of protein, lactose, solids-non-fat, total solids and IgG
      were comparable among groups. Results suggest a role for SCC, as an indicator of
      mastitis and colostral health quality, in affecting calf health. As a result of
      the novelty of calf health dependence on colostral SCC found, future studies to
      further characterize such relationships and to uncover or rule out possible
      mediators are required before colostral SCC could be recommended for routine on
      farm use in managing dry cow and calf production.

PMID- 20050957
TI  - A long-RP narrow QRS complex tachycardia with alternating cycle length: what is
      the mechanism?

PMID- 20050958
TI  - The modified anterior line: an alternative linear lesion in perimitral flutter.
AB  - INTRODUCTION: Ablation of left atrial flutter (LAF) is often limited by the need
      for technically demanding linear lesions. We evaluated the safety and efficacy of
      a new modified anterior line (MAL), connecting the anterior/anterolateral mitral
      annulus with the left superior pulmonary vein for ablation of perimitral flutter.
      METHODS AND RESULTS: MAL was performed in 65 patients (15 females, age 63.6 +/-
      9.8 years) with perimitral flutter using 3D mapping systems (70.8% Carto, 29.2%
      NavX). Perimitral flutter was either the presenting arrhythmia (73.8%) or an
      intermediate organized rhythm during atrial fibrillation ablation. Follow-up
      included repetitive 7-day Holter with 93.8% of patients off antiarrhythmics. MAL
      was acutely effective in 63/65 patients (96.9%). Termination to sinus rhythm
      occurred in 36 of 65 patients (55.4%), and in 27 of 65 patients (41.5%) there was
      a change to another LAF type. Bidirectional block across the MAL was achieved in
      56 of 65 patients (86.1%). After 6 months of follow-up, 20 of 41 patients (48.8%)
      had a LAF recurrence, with 6 patients undergoing a reablation. In all redo
      patients the MAL was still complete and LAF mechanism was different to the
      initially targeted. No major complication occurred during the ablation procedures
      or in the postablation period. CONCLUSION: The MAL is a safe and effective linear
      lesion for the treatment of perimitral LAF. Its value compared to more
      established linear lesions as the mitral isthmus line has to be evaluated in
      larger studies.

PMID- 20050959
TI  - The novel electrophysiology of complex fractionated atrial electrograms: insight
      from noncontact unipolar electrograms.
AB  - BACKGROUND: The noncontact mapping (NCM) system possesses the merit of global
      endocardial recording for unipolar and activation mapping. OBJECTIVE: We aimed to
      evaluate the unipolar electrogram characteristics and activation pattern over the
      bipolar complex fractionated atrial electrogram (CFAE) sites during atrial
      fibrillation (AF). METHODS: Twenty patients (age 55 +/- 11 years old, 15 males)
      who underwent NCM and ablation of AF (paroxysmal/persistent = 13/7) were
      included. Both contact bipolar (32-300 Hz) and NCM virtual unipolar electrograms
      (0.5-300 Hz) were simultaneously recorded along with the activation pattern
      (total 223 sites, 11 +/- 4 sites/patient). A CFAE was defined as a mean bipolar
      cycle length of <or= 120 ms with an intervening isoelectric interval of more than
      50 ms (Group 1A, n = 63, rapid repetitive CFAEs) or continuous fractionated
      activity (Group 1B, n = 59, continuous fractionated CFAEs), measured over a 7.2
      second duration. Group 2 consisted of those with a bipolar cycle length of more
      than 120 ms (n = 101). RESULTS: The Group 1A CFAE sites exhibited a shorter
      unipolar electrogram cycle length (129 +/- 11 vs 164 +/- 20 ms, P < 0.001), and
      higher percentage of an S-wave predominant pattern (QS or rS wave, 63 +/- 13% vs
      35 +/- 13%, P < 0.001) than the Group 2 non-CFAE sites. There was a linear
      correlation between the bipolar and unipolar cycle lengths (P < 0.001, R = 0.87).
      Most of the Group 1A CFAEs were located over arrhythmogenic pulmonary vein ostia
      or nonpulmonary vein ectopy with repetitive activations from those ectopies (62%)
      or the pivot points of the turning wavefronts (21%), whereas the Group 1B CFAEs
      exhibited a passive activation (44%) or slow conduction (31%). CONCLUSIONS: The
      bipolar repetitive and continuous fractionated CFAEs represented different
      activation patterns. The former was associated with an S wave predominant
      unipolar morphology which may represent an important focus for maintaining AF.

PMID- 20050960
TI  - Atrial resynchronization following heart transplantation in childhood.
AB  - Despite preserved left ventricular function, exercise capacity is often impaired
      after cardiac transplantation due to autonomic denervation of the donor's sinus
      node. We present our experience with atrio-atrial resynchronization in 2
      pediatric heart transplant recipients. Both were highly active, suffered from
      chronotropic incompetence, and underwent successful atrial resynchronization with
      an objective improvement in exercise capacity, restoration of a physiologic
      chronotropic response, and resolution of dyspnea. Long-term stable recipient
      sinus node function may, therefore, be maintained in some cardiac transplant
      recipients with standard atrio-atrial anastomes. Atrio-atrial pacing may be
      feasible and effective years after transplantation.

PMID- 20050961
TI  - Conduction delay in right ventricle as a marker for identifying high-risk
      patients with Brugada syndrome.
AB  - OBJECTIVES: To evaluate the significance of conduction delay (CD) in the right
      ventricle (RV) in Brugada syndrome (BS) as a marker for risk stratification of
      sudden death. METHODS: Twenty-five patients with BS (7 with documented
      ventricular fibrillation (VF), 8 with syncope, and 10 without symptoms) and 10
      control subjects were paced from the RV apex using 8 beats of drive pacing and a
      single extra-stimulus. CDs in the right ventricular outflow tract (RVOT) (CD-RV)
      and in the lateral left ventricle (L-LV) (CD-LV), and the local electrogram
      durations at a single extra-stimulus in RVOT (D-RV) and L-LV (D-LV) were
      calculated. We also evaluated changes in 12-lead ECG parameters in 16 patients
      with BS after pilsicainide challenge test (Pilsicainide-test). RESULTS: Maximal
      CD-RV and maximal D-RV were significantly larger than maximal CD-LV and maximal D
      LV in BS (26 +/- 10 and 105 +/- 15 vs 20 +/- 6 and 92 +/- 15 ms, P < 0.05,
      respectively). Maximal CD-RV and maximal D-RV in patients with documented VF were
      the largest among the 3 groups. There was a significant positive correlation
      between maximal CD-RV or maximal D-RV and changes in QRS duration in leads V2 and
      V5 and in S wave duration in lead II and V5 after Pilsicainide-test (CD-RV; r =
      0.54, 0.51, 0.56, and 0.53: D-RV; r = 0.55, 0.5, 0.57, and 0.53, P < 0.05,
      respectively). In control subjects, there were no significant differences.
      CONCLUSIONS: CD in RV was a useful marker for identifying high-risk patients with
      BS. CD in the RV, especially in the RVOT epicardium, may be related to
      arrhythmias in BS.

PMID- 20050962
TI  - Paroxysmal high-grade atrioventricular block and syncope in a previously healthy
      child: what is the mechanism?

PMID- 20050963
TI  - Cell interactions in bone tissue engineering.
AB  - Bone fractures, where the innate regenerative bone response is compromised,
      represent between 4 and 8 hundred thousands of the total fracture cases, just in
      the United States. Bone tissue engineering (TE) brought the notion that, in cases
      such as those, it was preferable to boost the healing process of bone tissue
      instead of just adding artificial parts that could never properly replace the
      native tissue. However, despite the hype, bone TE so far could not live up to its
      promises and new bottom-up approaches are needed. The study of the cellular
      interactions between the cells relevant for bone biology can be of essential
      importance to that. In living bone, cells are in a context where communication
      with adjacent cells is almost permanent. Many fundamental works have been
      addressing these communications nonetheless, in a bone TE approach, the 3D
      perspective, being part of the microenvironment of a bone cell, is as crucial.
      Works combining the study of cell-to-cell interactions in a 3D environment are
      not as many as expected. Therefore, the bone TE field should not only gain
      knowledge from the field of fundamental Biology but also contribute for further
      understanding the biology of bone. In this review, a summary of the main works in
      the field of bone TE, aiming at studying cellular interactions in a 3D
      environment, and how they contributed towards the development of a functional
      engineered bone tissue, is presented.

PMID- 20050964
TI  - High efficacy and minimal peptide required for the anti-angiogenic and anti
      hepatocarcinoma activities of plasminogen K5.
AB  - Kringle 5(K5) is the fifth kringle domain of human plasminogen and its anti
      angiogenic activity is more potent than angiostatin that includes the first four
      kringle fragment of plasminogen. Our recent study demonstrated that K5 suppressed
      hepatocarcinoma growth by anti-angiogenesis. To find high efficacy and minimal
      peptide sequence required for the anti-angiogenic and anti-tumour activities of
      K5, two deletion mutants of K5 were generated. The amino acid residues outside
      kringle domain of intact K5 (Pro452-Ala542) were deleted to form K5mut1(Cys462
      Cys541). The residue Cys462 was deleted again to form K5mut2(Met463-Cys541).
      K5mut1 specifically inhibited proliferation, migration and induced apoptosis of
      endothelial cells, with an apparent two-fold enhanced activity than K5.
      Intraperitoneal injection of K5mut1 resulted in more potent tumour growth
      inhibition and microvessel density reduction than K5 both in HepA-grafted and
      Bel7402-xenografted hepatocarcinoma mouse models. These results suggested that
      K5mut1 has more potent anti-angiogenic activity than intact K5. K5mut2, which
      lacks only the amino terminal cysteine of K5mut1, completely lost the activity,
      suggesting that the kringle domain is essential for the activity of K5. The
      activity was enhanced to K5mut1 level when five acidic amino acids of K5 in NH(2)
      terminal outside kringle domain were replaced by five serine residues (K5mut3).
      The shielding effect of acidic amino acids may explain why K5mut1 has higher
      activity. K5, K5mut1 and K5mut3 held characteristic beta-sheet spectrum while
      K5mut2 adopted random coil structure. These results suggest that K5mut1 with high
      efficacy is the minimal active peptide sequence of K5 and may have therapeutic
      potential in liver cancer.

PMID- 20050966
TI  - Why birds eat colourful grit: colour preferences revealed by the colour of
      gizzard stones.
AB  - Colour preferences from sexual or social contexts are assumed to have arisen
      owing to preferences for specific kinds of food, representing a sensory bias, but
      once colour preferences have evolved in a sexual context, they may also be
      expressed during foraging. We tested whether preferences for specific body
      colours (i.e. plumage and soft parts) were related to colour preferences for grit
      ingested by birds. Birds eat grit to facilitate break down of food by the
      gizzard, and this function is independent of the colour of grit, but depends on
      the physical properties of stones. Bird species were significantly consistent in
      colour of grit, and grit of different colours varied in prevalence among species,
      even when analyses were restricted to a sample from a single locality. There were
      positive correlations between presence of lilac and red grit in the gizzard and
      presence of sexually dichromatic lilac and red colour on the body. There was a
      positive correlation between red grit colour and red sexually monochromatic body
      colour. Bird species with many different sexual colours, but not sexually
      monochromatic colours on their body had many different colours of grit. Males had
      more lilac and red grit than females, with this effect differing among species,
      whereas that was not the case for grit of other colours. These findings are
      consistent with the sensory bias hypothesis that birds express preferences for
      grit of specific colours and a high diversity of colours related to sexual
      colouration of the body, even when the colour of such grit is only visible to the
      individual at the moment of ingestion.

PMID- 20050965
TI  - Longitudinal pathways linking child maltreatment, emotion regulation, peer
      relations, and psychopathology.
AB  - BACKGROUND: The aim of this study was to investigate longitudinal relations among
      child maltreatment, emotion regulation, peer acceptance and rejection, and
      psychopathology. METHODS: Data were collected on 215 maltreated and 206
      nonmaltreated children (ages 6-12 years) from low-income families. Children were
      evaluated by camp counselors on emotion regulation and internalizing and
      externalizing symptomatology and were nominated by peers for peer acceptance and
      rejection. RESULTS: Structural equation modeling analyses revealed that
      experiencing neglect, physical and/or sexual abuse, multiple maltreatment
      subtypes, and earlier onset of maltreatment were related to emotion
      dysregulation. Lower emotion regulation (Time 1) was associated with higher
      externalizing symptomatology (Time 1) that contributed to later peer rejection
      (Time 2), which in turn was related to higher externalizing symptomatology (Time
      2). Conversely, higher emotion regulation was predictive of higher peer
      acceptance over time, which was related to lower internalizing symptomatology
      controlling for initial levels of symptomatology. CONCLUSIONS: The findings
      emphasize the important role of emotion regulation as a risk or a protective
      mechanism in the link between earlier child maltreatment and later
      psychopathology through its influences on peer relations.

PMID- 20050967
TI  - Iridovirus infections in finfish - critical review with emphasis on ranaviruses.
AB  - Viruses in three genera of the family Iridoviridae (iridoviruses) affect finfish.
      Ranaviruses and megalocytiviruses are recently emerged pathogens. Both cause
      severe systemic disease, occur globally and affect a diversity of hosts. In
      contrast, lymphocystiviruses cause superficial lesions and rarely cause economic
      loss. The ranavirus epizootic haematopoietic necrosis virus (EHNV) from Australia
      was the first iridovirus to cause epizootic mortality in finfish. Like other
      ranaviruses, it lacks host specificity. A distinct but closely related virus,
      European catfish virus, occurs in finfish in Europe, while very similar
      ranaviruses occur in amphibians in Europe, Asia, Australia, North America and
      South America. These viruses can be distinguished from one another by conserved
      differences in the sequence of the major capsid protein gene, which informs
      policies of the World Organisation for Animal Health to minimize transboundary
      spread of these agents. However, limited epidemiological information and
      variations in disease expression create difficulties for design of sampling
      strategies for surveillance. There is still uncertainty surrounding the taxonomy
      of some putative ranaviruses such as Singapore grouper iridovirus and Santee
      Cooper ranavirus, both of which cause serious disease in fish, and confusion
      continues with diseases caused by megalocytiviruses. In this review, aspects of
      the agents and diseases caused by ranaviruses are contrasted with those due to
      megalocytiviruses to promote accurate diagnosis and characterization of the
      agents responsible. Ranavirus epizootics in amphibians are also discussed because
      of possible links with finfish and common anthropogenic mechanisms of spread. The
      source of the global epizootic of disease caused by systemic iridoviruses in
      finfish and amphibians is uncertain, but three possibilities are discussed: trade
      in food fish, trade in ornamental fish, reptiles and amphibians and emergence
      from unknown reservoir hosts associated with environmental change.

PMID- 20050968
TI  - Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative
      disease.
AB  - To investigate the role of the Wnt inhibitor Dickkopf-1 (DKK-1) in the
      pathophysiology of neurodegenerative diseases, we analysed DKK-1 expression and
      localization in transgenic mouse models expressing familial Alzheimer's disease
      mutations and a frontotemporal dementia mutation. A significant increase of DKK-1
      expression was found in the diseased brain areas of all transgenic lines, where
      it co-localized with hyperphosphorylated tau-bearing neurons. In TgCRND8 mice,
      DKK-1 immunoreactivity was detected in neurons surrounding amyloid deposits and
      within the choline acetyltransferase-positive neurons of the basal forebrain.
      Active glycogen synthase kinase-3 (GSK-3) was found to co-localize with DKK-1 and
      phospho-tau staining. Downstream to GSK-3, a significant reduction in beta
      catenin translocation to the nucleus, indicative of impaired Wnt signaling
      functions, was found as well. Cumulatively, our findings indicate that DKK-1
      expression is associated with events that lead to neuronal death in
      neurodegenerative diseases and support a role for DKK-1 as a key mediator of
      neurodegeneration with therapeutic potential.

PMID- 20050969
TI  - Prosaposin in the secretome of marrow stroma-derived neural progenitor cells
      protects neural cells from apoptotic death.
AB  - Functionally, adult stem cells not only participate in replication and
      differentiation to various cell lineages, but also may be involved in rescuing
      cells from apoptosis. Identifying functional factors secreted by stem cells, as
      well as their target cells, may advance our understanding of stem cells'
      multifaceted physiologic functions. Here, we report that mouse bone marrow
      stromal cell-derived neuroprogenitor cells (mMSC-NPC) provide a protective
      function by secreting a key factor, prosaposin (PSAP), capable of rescuing mature
      neurons from apoptotic death. This factor is identified as the lead protein in
      the secretome of mMSC-NPC cultures by tandem mass spectroscopic profiling, and
      further validated by western blotting and immunocytochemistry. The secretome of
      MSC-NPC reduces toxin-induced cell death in cultures of rat pheochromocytoma
      neuronal cells, human ReNcell CX neurons, and rat cortical primary neurons;
      removal of PSAP by immunodepletion annuls this protective effect. This neuronal
      protection against toxin treatment was validated further by the recombinant PSAP
      peptide. Interestingly, the secretome of neuronal culture does not possess such a
      self-protective action. We suggest that upon injury, a subgroup of MSCs
      differentiates into neural/neuronal progenitor cells, and remains in this
      intermediate stem cell-like stage, defending injured neighboring mature neurons
      from apoptosis by secreting PSAP.

PMID- 20050970
TI  - Resveratrol reduces glutamate-mediated monocyte chemotactic protein-1 expression
      via inhibition of extracellular signal-regulated kinase 1/2 pathway in rat
      hippocampal slice cultures.
AB  - Published evidence has linked glutamate with the pathogenesis of Alzheimer's
      disease (AD) and the up-regulation of a variety of chemokines, including monocyte
      chemotactic protein-1 (MCP-1)/chemokine ligand 2, with AD-associated pathological
      changes. In this study, we assessed the potential molecular basis for the role of
      glutamate in hippocampal inflammation by determining its effects on MCP-1
      induction. We also attempted to identify the mechanism by which resveratrol
      (trans-3,5,4'-trihydroxystilbene), a polyphenolic phytostilbene, modulates the
      expression of MCP-1 in the glutamate-stimulated hippocampus. An ex vivo study
      using rat hippocampal slices demonstrated a time- and dose-dependent increase in
      MCP-1 release from glutamate-exposed hippocampus. This increase was accompanied
      by enhanced MCP-1 gene expression via the activation of the MEK/extracellular
      signal-regulated kinase (ERK) pathway and interleukin-1beta (IL-1beta)
      expression. The inhibition of the MEK/ERK pathway with SL327, which is capable of
      crossing the blood-brain barrier, nearly abolished the observed glutamate-induced
      effects. Furthermore, anti-IL-1beta antibodies suppressed the glutamate-induced
      expression of MCP-1 mRNA and protein, whereas an isotype-matched antibody exerted
      only minimal effects. It is worthy of note that resveratrol, to a similar degree
      as SL327, down-regulated glutamate-induced IL-1beta expression and reduced the
      expression of MCP-1 mRNA and protein release via the inactivation of ERK1/2.
      These results indicate that the activation of the MEK/ERK pathway and the
      consequent IL-1beta expression are essential for glutamate-stimulated MCP-1
      production in the hippocampus. Additionally, our data reveal an anti-inflammatory
      mechanism of resveratrol involving the inactivation of the ERK1/2 pathway in the
      hippocampus, which is linked principally to AD-associated cognitive dysfunction.

PMID- 20050971
TI  - Differential sensitivity of the inner ear sensory cell populations to forced cell
      cycle re-entry and p53 induction.
AB  - Previous studies have shown that the maintenance of post-mitotic state is
      critical for the life-long survival of the inner ear mechanosensory cells, the
      hair cells. A general concept is that differentiated, post-mitotic cells rapidly
      die following cell cycle re-entry. Here we have compared the response of
      postnatal cochlear (auditory) and utricular (balance) hair cells to forced cell
      cycle reactivation and p53 up-regulation. Forced S-phase entry was triggered
      through the human papillomavirus-16 E7 oncogene misexpression in explant
      cultures. It induced DNA damage and p53 induction in cochlear outer hair cells
      and these cells were rapidly lost, before entry into mitosis. The death was
      attenuated by p53 inactivation. In contrast, despite DNA damage and p53
      induction, utricular hair cells showed longer term survival and a proportion of
      them progressed into mitosis. Consistently, pharmacological elevation of p53
      levels by nutlin-3a led to a death-prone phenotype of cochlear outer hair cells,
      while other hair cell populations were death-resistant. These data have important
      clinical implications as they show the importance of p53 in sensory cells that
      are essential in hearing function.

PMID- 20050972
TI  - Naturally occurring phytochemicals for the prevention of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disease increasingly
      recognized as one of the most important medical problems affecting the elderly.
      Although a number of drugs, including several cholinesterase inhibitors and an
      NMDA receptor antagonist, have been approved for use, they have been shown to
      produce diverse side effects and yield relatively modest benefits. To overcome
      these limitations of current therapeutics for AD, extensive research and
      development are underway to identify drugs that are effective and free of
      undesirable side effects. Certain naturally occurring dietary polyphenolic
      phytochemicals have received considerable recent attention as alternative
      candidates for AD therapy. In particular, curcumin, resveratrol, and green tea
      catechins have been suggested to have the potential to prevent AD because of
      their anti-amyloidogenic, anti-oxidative, and anti-inflammatory properties. These
      polyphenolic phytochemicals also activate adaptive cellular stress responses,
      called 'neurohormesis', and suppress disease processes. In this commentary, we
      describe the amyloid-beta-induced pathogenesis of AD, and summarize the
      intracellular and molecular targets of selected dietary phytochemicals that might
      slow the progression of AD.

PMID- 20050974
TI  - MicroRNA-92 modulates K(+) Cl(-) co-transporter KCC2 expression in cerebellar
      granule neurons.
AB  - MicroRNAs have been associated to fine-tuning spatial and temporal control of
      gene expression during neuronal development. The neuronal Cl(-) extruding,
      K(+)Cl(-) co-transporter 2 (KCC2) is known to play an important role in neuronal
      Cl(-) homeostasis and in determining the physiological response to activation of
      anion selective GABA receptors. Here we show that microRNA-92 is developmentally
      down-regulated during maturation of rat cerebellar granule neurons (CGNs) in
      vitro. Computational predictions suggest several high-ranking targets for
      microRNA-92 including the KCC2 gene. Consistently, the KCC2 protein levels were
      up-regulated in mature CGN in vitro and a functional association between microRNA
      92 and KCC2 3' untranslated region was established using luciferase assays. The
      generation of an inward directed Cl(-) electrochemical gradient, necessary for
      the hyperpolarizing effect of GABA, requires robust KCC2 expression in several
      neuronal types. Here we show that lentiviral-mediated microRNA-92 over-expression
      reduced KCC2 protein levels and positively shifted reversal potential of GABA
      induced Cl(-) currents in CGNs. In addition KCC2 re-expression reversed microRNA
      92 electrophysiological phenotype. Consistently microRNA-92 inhibition induced
      both an increase of the level of KCC2 and a negative shift in GABA reversal
      potential. These findings introduce a new player in the developmental change of
      GABA from depolarization to hyperpolarization.

PMID- 20050973
TI  - Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway.
AB  - Recently more evidences support baicalein (Bai) is neuroprotective in models of
      ischemic stroke. This study was conducted to determine the molecular mechanisms
      involved in this effect. Either permanent or transient (2 h) middle cerebral
      artery occlusion (MCAO) was induced in rats in this study. Permanent MCAO led to
      larger infarct volumes in contrast to transient MCAO. Only in transient MCAO, Bai
      administration significantly reduced infarct size. Baicalein also markedly
      reduced apoptosis in the penumbra of transient MCAO rats. Additionally, oxygen
      and glucose deprivation (OGD) was used to mimic ischemic insult in primary
      cultured cortical neurons. A rapid increase in the intracellular reactive oxygen
      species level and nitrotyrosine formation induced by OGD was counteracted by Bai,
      which is parallel with attenuated cell injury. The reduction of phosphorylation
      Akt and glycogen synthase kinase-3beta (GSK3beta) induced by OGD was restored by
      Bai, which was associated with preserved levels of phosphorylation of PTEN, the
      phophatase that negatively regulates Akt. As a consequence, Bcl-2/Bcl-xL
      associated death protein phosphorylation was increased and the protein level of
      Bcl-2 in motochondria was maintained, which subsequently antagonize cytochrome c
      released in cytosol. LY294002 blocked the increase in phospho-AKT evoked by Bai
      and abolished the associated protective effect. Together, these findings provide
      evidence that Bai protects neurons against ischemia injury and this
      neuroprotective effect involves PI3K/Akt and PTEN pathway.

PMID- 20050975
TI  - Oligomerization in the endoplasmic reticulum and intracellular trafficking of
      kainate receptors are subunit-dependent but not editing-dependent.
AB  - Investigating subunit assembly of ionotropic glutamate receptor complexes and
      their trafficking to the plasma membrane under physiological conditions in live
      cells has been challenging. By confocal imaging of fluorescently labeled kainate
      receptor (KAR) subunits combined with digital co-localization and fluorescence
      resonance energy (FRET) transfer analyses, we investigated the assembly of
      homomeric and heteromeric receptor complexes and identified the subcellular
      location of subunit interactions. Our data provide direct evidence for
      oligomerization of KAR subunits as early as following their biosynthesis in the
      endoplasmic reticulum (ER). These oligomeric assemblies pass through the Golgi
      apparatus en route to the plasma membrane. We show that the amino acid at the Q/R
      editing site of the KAR subunit GluR6 neither determines subunit oligomerization
      in the ER nor ER exit or plasma membrane expression, and that it does not alter
      GluR6 interaction with KA2. This finding sets KARs apart from alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, where in the absence of
      auxiliary proteins Q isoforms exit the ER much more efficiently than R isoforms.
      Furthermore, although KA2 subunits do not form functional homotetrameric
      complexes, we visualized their oligomerization (at least dimerization) in the ER.
      Finally, we demonstrate that plasma membrane expression of GluR6/KA2 heteromeric
      complexes is modulated not only by GluR6 but also KA2.

PMID- 20050976
TI  - An update on clinical proteomics in Alzheimer's research.
AB  - Alzheimer's disease (AD) is a pathologically complex and aetiologically
      multifactorial dementing disorder affecting millions of people worldwide. The
      pathological brain changes are assumed to occur decades prior to the onset of
      clinical symptoms. The diagnosis of early AD remains problematic and is mainly
      based on clinical and neuropsychological findings after the onset of symptoms.
      Currently available drugs are able to delay the symptom progression of the
      disease but not to attenuate the progression of pathological brain changes. Many
      studies exploring AD proteomes have been conducted as the middle of 1990s as a
      consequence of recent advances in the development of both gel-based and gel-free
      proteomics approaches. It is hoped that proteomics can contribute to improving
      the understanding, diagnosis, and follow-up of the progression of AD. In this
      review, we summarise the present status of proteome alterations, with emphasis on
      quantitative approaches, in AD brain, CSF and blood, and their relevance to
      dementia research.

PMID- 20050977
TI  - The endogenous cannabinoid, anandamide, inhibits dopamine transporter function by
      a receptor-independent mechanism.
AB  - The endocannabinoid, anandamide (AEA), modulates the activity of the dopamine
      transporter (DAT) in heterologous cells and synaptosomal preparations. The
      cellular mechanisms mediating this effect are unknown. The present studies
      employed live cell imaging techniques and the fluorescent, high affinity DAT
      substrate, 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP(+)), to address
      this issue. AEA addition to EM4 cells expressing yellow fluorescent protein
      tagged human DAT (hDAT) produced a concentration-dependent inhibition of ASP(+)
      accumulation (IC(50): 3.2 +/- 0.8 microM). This effect occurred within 1 min
      after AEA addition and persisted for 10 min thereafter. Pertussis toxin did not
      attenuate the effects of AEA suggesting a mechanism independent of G(i)/G(o)
      coupled receptors. The amidohydrolase inhibitor, phenylmethylsulfonyl fluoride
      (0.2 mM), failed to alter the AEA-evoked inhibition of ASP(+) accumulation.
      Methanandamide (10 microM), a metabolically stable analogue of AEA inhibited
      accumulation but arachidonic acid (10 microM) was without effect suggesting that
      the effects of AEA are not mediated by its metabolic products. The extent of AEA
      inhibition of ASP(+) accumulation was not altered in cells pre-treated with 1
      microM URB597, a specific and potent fatty acid amide hydrolase inhibitor, and
      the cyclooxygenase inhibitor, indomethacin (5 microM) Live cell imaging revealed
      a significant redistribution of hDAT from the membrane to the cytosol in response
      to AEA treatment (10 microM; 10 min). Similarly biotinylation experiments
      revealed that the decrease in DAT function was associated with a reduction in
      hDAT cell surface expression. These results demonstrate that AEA modulates DAT
      function via a cannabinoid receptor-independent mechanism and suggest that AEA
      may produces this effect, in part, by modulating DAT trafficking.

PMID- 20050978
TI  - L-DOPA-induced dopamine efflux in the striatum and the substantia nigra in a rat
      model of Parkinson's disease: temporal and quantitative relationship to the
      expression of dyskinesia.
AB  - L-DOPA-induced dyskinesia in Parkinson's disease is associated with large
      increases in brain dopamine (DA) levels following drug dosing, but the precise
      significance of this phenomenon is not understood. Here we compare DA efflux and
      metabolism in the striatum and the substantia nigra in dyskinetic and non
      dyskinetic animals following a standard dose of L-DOPA. Rats with 6
      hydroxydopamine lesions were treated chronically with L-DOPA, monitored on the
      abnormal involuntary movements scale, and then subjected to intracerebral
      microdialysis under freely-moving conditions. Following s.c. L-DOPA injection,
      peak extracellular DA levels in both striatum and substantia nigra were about
      twice as large in dyskinetic animals compared to non-dyskinetic rats. This effect
      was not attributable to differences in DOPA levels or DA metabolism. The larger
      DA efflux in dyskinetic animals was blunted by 5-HT1A/5-HT1B receptor agonists
      and tetrodotoxin infusion, reflecting release from serotonin neurons. Striatal
      levels of serotonin and its main metabolite, 5-hydroxyindolacetic acid were
      indeed elevated in dyskinetic animals compared to non-dyskinetic rats, indicating
      a larger serotonergic innervation density in the former group. High DA release
      was, however, not sufficient to explain dyskinesia. The 'abnormal involuntary
      movements output' per unit concentration of striatal extracellular DA was indeed
      much larger in dyskinetic animals compared to non-dyskinetic cases at most time
      points examined. The present results indicate that both a high DA release post-L
      DOPA administration and an increased responsiveness to DA must coexist for a full
      expression of dyskinesia.

PMID- 20050979
TI  - Balanced effect of PACAP and FasL on granule cell death during cerebellar
      development: a morphological, functional and behavioural characterization.
AB  - It is now established that the development of the CNS requires equilibrium
      between cell survival and apoptosis. Pituitary adenylate cyclase-activating
      polypeptide (PACAP) exerts a powerful protective effect on cerebellar granule
      cells by inhibiting the caspase 3. In contrast, Fas ligand (FasL) plays an
      essential role during ontogenesis in eliminating supernumerary neurons by
      apoptosis. To determine if PACAP and FasL interact during cerebellar development,
      we characterized the effects of these factors on cerebellar morphogenesis and
      caspase 3 activity in PACAP+/+ and PACAP-/- mice. First, we demonstrated in vivo
      that PACAP is able to reverse the diminution of internal granule cell layer
      thickness induced by FasL in PACAP+/+ and PACAP-/- mice. Second, ex vivo and
      immunohistochemical studies revealed that interaction between FasL and PACAP
      occurs through the caspase 3 activity. Third, behavioural study showed a
      significant difference for the PACAP + FasL group in the righting reflex test at
      P8 which does not persist at P60. Finally, a time course study revealed that the
      pro-apoptotic effect of FasL characterized at P8 was followed by a progressive
      compensatory mechanism in caspase 3 activity and bromodeoxyuridine incorporation.
      These data suggest that PACAP and FasL interact during cerebellar development to
      control apoptosis of granule cells and may affect some motor cerebellar
      functions.

PMID- 20050980
TI  - Co-operativity in agonist binding at the D2 dopamine receptor: evidence from
      agonist dissociation kinetics.
AB  - There is much evidence to suggest that G protein coupled receptors exist as
      oligomers but the relevance to their function is unclear. We have, therefore,
      examined the binding of the radiolabelled agonist [(3)H]NPA to membranes of CHO
      cells expressing the D(2) dopamine receptor in dissociation rate experiments.
      When [(3)H]NPA dissociation was started by dilution, the dissociation rate in the
      absence of sodium ions was unaffected by addition of the antagonist/inverse
      agonist (+)-butaclamol, but was accelerated by addition of agonists e.g.
      dopamine, suggesting that the receptor was not behaving as a monomer with a
      single binding site. The very low efficacy partial agonist, aripiprazole provided
      an intermediate level of acceleration of dissociation. [(3)H]NPA dissociation
      experiments started by addition of ligands without dilution gave a similar
      pattern. [(3)H]NPA dissociation could also be accelerated by GTP. Dissociation of
      [(3)H]NPA in the presence of GTP and dopamine provided a greater acceleration
      than for either modulator alone, suggesting synergistic effects related to
      receptor/G protein interaction. When [(3)H]NPA dissociation experiments were
      performed in the presence of sodium ions, dissociation was faster than in their
      absence but the rate still depended on the ligand present in the assay. Overall
      the data cannot be explained by a ternary complex model and are consistent with
      an oligomeric receptor in which binding of [(3)H]NPA, as an example of an agonist
      ligand, can be modulated co-operatively by ligands binding elsewhere in the
      oligomer. Interactions with G proteins also occurs providing further modulation
      of [(3)H]NPA binding. Both agonists and G proteins are proposed to modulate the
      oligomer by switching high affinity agonist binding sites to low affinity sites.

PMID- 20050981
TI  - Evaluation of survivin as a prognostic marker in oral squamous cell carcinoma.
AB  - BACKGROUND: Poor prognosis of oral squamous cell carcinoma (OSCC) is partly
      attributed to the lack of significant tumor marker for accurate staging and
      prognostication. We have evaluated survivin, which is a member of the inhibitor
      of apoptosis family as a cancer marker associated with proliferation,
      angiogenesis, oral carcinogenesis, and OSCC patient survival, as we reported a
      prognostic significance of survivin expression in lymph node previously. METHODS:
      To evaluate survivin expression in six OSCC cell lines, Western blotting was
      performed. Hamster oral carcinogenesis model was used to observe changes of
      survivin expression in oral carcinogenesis. Finally, we assessed the diagnostic
      and prognostic significance of survivin in a series of 38 primary OSCC through
      immunohistochemistry (CD31, PCNA) and Kaplan-Meier's test. RESULTS: Survivin
      expression was detected in all OSCC cell lines at a varying level but not
      observed in normal gingival keratinocyte cells. In hamster model, survivin
      expression was observed from 8 weeks through 16 weeks and the intensity of
      expression became strong until 16 weeks. Clinicopathological analysis revealed a
      significant correlation between survivin expression and lymph node metastasis (P
      = 0.006) and proliferation (P < 0.001). However, there was no significant
      relationship with differentiation, micro vessel density, and cancer stage based
      on TNM. Survivin overexpression had a significant negative effect on survival of
      patients. CONCLUSIONS: These results demonstrate the significant relationship
      between survivin expression and oral carcinogenesis and aggressiveness of OSCC
      including survival rate of patient. Survivin therefore may be used as a
      significant cancer marker to gain prognostic information of OSCC.

PMID- 20050983
TI  - Exploratory factor analysis of the Brazilian OHIP for edentulous subjects.
AB  - The use of seven domains for the Oral Health Impact Profile (OHIP)-EDENT was not
      supported for its Brazilian version, making data interpretation in clinical
      settings difficult. Thus, the aim of this study was to assess patients' responses
      for the translated OHIP-EDENT in a group of edentulous subjects and to develop
      factor scales for application in future studies. Data from 103 conventional and
      implant-retained complete denture wearers (36 men, mean age of 69.1 +/- 10.3
      years) were assessed using the Brazilian version of the OHIP-EDENT. Oral health
      related quality of life domains were identified by factor analysis using
      principal component analysis as the extraction method, followed by varimax
      rotation. Factor analysis identified four factors that accounted for 63% of the
      19 items total variance, named masticatory discomfort and disability (four
      items), psychological discomfort and disability (five items), social disability
      (five items) and oral pain and discomfort (five items). Four factors/domains of
      the Brazilian OHIP-EDENT version represent patient-important aspects of oral
      health-related quality of life.

PMID- 20050982
TI  - Rigid confocal endoscopy for in vivo imaging of experimental oral squamous intra
      epithelial lesions.
AB  - BACKGROUND: A rigid confocal endoscope has been developed to assess the oral
      squamous epithelium of mice and to determine sensitivity, specificity, and
      accuracy of this new technology. METHODS: This endoscope is connected to the
      commercially available Heidelberg Retina Tomograph (HRT). HRT is a device with a
      670-nm diode laser designed to acquire topographical measurements of the optic
      nerve head. Real-time rigid confocal endoscopy is demonstrated by imaging the
      epithelial lesions of a mice model. Six-week-old male C57Bl/6 mice were randomly
      divided into a non-treated group (n = 10) and into a 4-nitroquinoline 1-oxide (4
      NQO)-treated group (n = 50). In the 4-NQO-treated group, the mice obtained 4
      nitroquinoline 1-oxide in the drinking water (100 microg/ml) to induce
      tumourigenesis in the mouse tongue. The 4-NQO-solution was diluted in the
      drinking water for mice. After an 8-16-week carcinogen treatment with 4-NQO (ad
      libitum), mouse tongues were dissected within 3 h after CO(2) overdose. After
      confocal microscopy of all lesions of the tongue, conventional histopathological
      investigation was performed. RESULTS: The inter-rater reliability for the two
      observers of the confocal microscopic findings was found to be Kappa = 0.59 (P <
      0.001). The penetration depth varied in the healthy tissue of the underside of
      the tongue throughout this study and was measured between 104 and 240 microm. In
      keratotic lesions, the penetration depths were diminished and varied between 80
      and 140 microm. Strong keratinization inhibits the evaluation of the epithelium.
      For differentiation between low-grade and high-grade squamous intra-epithelial
      lesions, a sensitivity and specificity of 73% and 88% was reached. CONCLUSIONS:
      The animal experiment with this non-invasive new technology indicates that this
      imaging technology facilitates the detection of pre-cancerous lesions of the
      underside of the oropharynx. Human studies on oropharyngeal and laryngeal lesions
      are needed to prove the applicability of this method in the field of
      otorhinolaryngology.

PMID- 20050984
TI  - Mandibular Kennedy Class I implant-tooth-borne removable partial denture: a
      systematic review.
AB  - The purpose of this systematic review is to evaluate the use of implant-tooth
      borne removable partial dentures in prosthetic rehabilitation of Kennedy Class I
      partially edentulous arches. A comprehensive search was performed in MEDLINE,
      EMBASE, Cochrane Oral Health Group's Trials Register, Cochrane Central Register
      of Controlled Trials, UK National Research Register, Australian New Zealand
      Clinical Trials Registry (ANZCTR), conference proceedings and abstracts up to 25
      August 2009. Searching the reference list of the selected articles and hand
      searching of several journals were also performed. A total of nine studies were
      included. Of these, two were randomized, three were retrospective and four were
      case reports. All but two had a low reporting quality (level IV on a four-level
      hierarchy of evidence). Nevertheless, the improvement in function, aesthetics and
      stability has been demonstrated in all studies with minimal prosthetic care.
      Within the limitations of this study, implant-assisted/supported removable
      partial denture may provide a simple, economical and less invasive treatment
      modality. The predictability of such approach in the management of bilateral
      distal-extension situation is, however, still questionable. A higher quality of
      published studies namely with a focus on long-term randomized clinical trials are
      needed.

PMID- 20050985
TI  - Oral environmental factors affecting number of microbes in saliva of complete
      denture wearers.
AB  - The purpose of this study was to clarify which oral environmental factors
      affected number of microbes in saliva in an edentulous environment. We enrolled
      68 edentulous subjects in the study. Numbers of total anaerobic bacteria and
      Candida species in saliva were determined. Age, sex, un-stimulated salivary flow
      rate, pH and viscosity of saliva, histatin level in saliva, tongue coating
      status, tongue pressure, denture plaque status, material of denture base,
      duration of edentulism, frequency of self oral health care and number of
      cigarettes per day were also investigated as oral environmental factors.
      Correlation between number of total anaerobic bacteria or Candida species and
      each oral environmental factor was determined with the Spearman rank correlation
      coefficient. Stepwise logistic regression analysis was used to identify which
      factors were significantly associated with level of total anaerobic bacteria and
      Candida species. Correlation and stepwise logistic regression analyses revealed
      associations between un-stimulated salivary flow rate, tongue coating status,
      denture plaque status or frequency of self oral health care and number of total
      anaerobic bacteria. The correlation analysis showed a significant correlation
      between age and number of total anaerobic bacteria. Stepwise logistic analysis
      revealed associations between pH of saliva or viscosity of saliva and level of
      anaerobic bacteria; it also revealed associations between histatin level in
      saliva or un-stimulated salivary flow rate and level of Candida species. We
      conclude that salivary flow rate, in particular, affects number of salivary
      microbes in an edentulous environment.

PMID- 20050986
TI  - Does long-term use of unstable dentures weaken jaw muscles?
AB  - Although it is well known that conventional denture wearers have lower maximum
      bite forces than dentate subjects, no previous studies have compared the strength
      of the jaw muscles between these two groups. This study compared maximum bite
      forces, electromyographic (EMG) activity and estimated jaw muscle strength among
      three groups: (i) 17 edentulous subjects using newly acquired implant-retained
      overdentures (seven men, 10 women; mean age 60.3 +/- 13.0 years); (ii) 10 age
      matched, fully dentate subjects (five men, five women; mean age 57.9 +/- 11.0
      years); and (iii) 39 young, fully dentate subjects (19 men, 20 women; mean age
      24.4 +/- 3.5 years). Electromyographic activity was recorded from subjects'
      bilateral superficial masseter and anterior temporalis muscles while they
      generated maximum voluntary bite forces at the right central incisor, right first
      premolar and right first molar positions. Jaw muscle strength was estimated as
      the ratio of average EMG activity for all four muscles to the maximum bite force.
      At all three bite positions, edentulous subjects produced maximum bite forces
      that were less than half that of dentate subjects. Edentulous subjects also
      produced significantly less EMG activity and had significantly lower estimated
      jaw muscle strength. Our results suggest that weakened jaw muscles are one factor
      contributing to lower maximum bite forces among users of conventional dentures.

PMID- 20050987
TI  - Effect of pre-heating on the viscosity and microhardness of a resin composite.
AB  - The effect of pre-heating resin composite on pre-cured viscosity and post-cured
      surface hardness was evaluated. Groups of uncured specimens were heated to 60
      degrees C and compared with control groups (24 degrees C) with respect to
      viscosity and surface hardness. Mean (SD) viscosities of the pre-heated specimens
      (n = 15) were in the range of 285 (13)-377 (11) (Pa) compared with 642 (35)-800
      (23) (Pa) at ambient temperature. There was a statistically significant
      difference between the two groups (P < 0.001). Mean (SD) Vickers microhardness
      (VHN) of the pre-heated group (n = 15) was 68.6 (2.3) for the top surface and
      68.7 (1.8) for the bottom surface measured at 24 h post curing (specimen
      thickness = 1.5 mm). The corresponding values for the room temperature group were
      60.6 (1.4) and 59.0 (3.5). There was a statistically significant difference
      between corresponding measurements taken at the top and bottom for the pre-heated
      and room temperature groups (P < 0.001). There was no significant difference
      between top and bottom measurements within each group. Pre-heating resin
      composite reduces its pre-cured viscosity and enhances its subsequent surface
      hardness. These effects may translate as easier placement together with an
      increased degree of polymerization and depth-of-cure.

PMID- 20050988
TI  - Association of disease-predisposition polymorphisms of the melatonin receptors
      and sunshine duration in the global human populations.
AB  - Melatonin is predominantly involved in signaling circadian and seasonal rhythms,
      and its synthesis is regulated by the environmental light/dark cycle. The
      selection pressure by geographically different environmental light/dark cycles,
      which is predominantly determined by sunshine duration, on the global
      distribution of genetic polymorphisms in the melatonin pathway is not well
      understood. Recent genetic association studies identified various disease
      predisposition polymorphisms in this pathway. We investigated the correlations
      between the prevalence of these clinically important single nucleotide
      polymorphisms (SNPs) and sunshine duration among worldwide human populations from
      twelve regions in the CEPH-HGDP database rs4753426, a recently reported
      predisposition SNP for type 2 diabetes in the promoter of the MT(2) melatonin
      receptor gene (MTNR1B), which was not included in the CEPH-HGDP genotyping array,
      was additionally genotyped. This SNP showed a marginally significant correlation
      in 760 CEPH-HGDP DNA samples (r = -0.5346, P = 0.0733), and it showed the most
      prominent association among the candidate melatonin pathway SNPs examined. To
      control for population structure, which may lead to a false positive correlation,
      we genotyped this SNP in a replication set of 1792 subjects from China. The
      correlation was confirmed among Chinese populations (r = -0.8694, P = 0.0002),
      and was also statistically significant after correction of other climatic and
      geographical covariants in multiple regression analysis (beta = -0.907, P = 1.94
      x 10(-5)). Taken together, it suggests that the human melatonin signaling
      pathway, particularly MT(2) melatonin receptor may have undergone a selective
      pressure in response to global variation in sunshine duration.

PMID- 20050989
TI  - Beneficial effects of melatonin on nicotine-induced vasculopathy.
AB  - Tobacco smoking is responsible for death of many people each year and increases
      the risk of developing numerous disorders, particularly cardiovascular disease
      and cancer. Among the components of cigarette smoke, nicotine is known to excert
      proatherosclerotic, prothrombotic and proangiogenic effects on vascular
      endothelial cells. The current study was designed to investigate the mechanisms
      by which nicotine induces endothelial dysfunction and further to examine whether
      melatonin protects against nicotine-induced vasculopathy. Four groups of male
      rats (controls, melatonin-treated, nicotine treated [100 microg/mL in drinking
      water], and nicotine plus melatonin [5 mg/kg/day] treated) were used in this
      study. After 28 days all the animals were killed by decapitation and the aorta
      was removed. We evaluated the hydroxyproline content, and the different
      expression of proteins involved in several types of stress (ERK1/2), in fibrosis
      (TGF-beta1, NF-kappaB) and in recruitment of circulating leukocytes onto the
      vessel wall, including intercellular adhesion molecule-1 (ICAM-1) and vascular
      cellular adhesion molecule-1 (VCAM-1). These metabolic pathways are important in
      the development of nicotine-induced atherosclerosis and hypertension. Our results
      show that nicotine induces marked structural and functional alterations in the
      aorta. Nicotine receptor binding results in activation and phosphorylation of ERK
      1/2. This enzyme, in turn, activates both TGF-beta1 and NF-kappaB; they stimulate
      respectively the synthesis of type I collagen, responsible of fibrosis, and
      moreover ICAM-1, VCAM-1 and reactive oxygen species. Based on these findings,
      melatonin is able to minimize the negative effects of nicotine by blocking the
      activation of ERK and the other signalling pathways in which this enzyme is
      involved.

PMID- 20050990
TI  - The protective effect of melatonin on methamphetamine-induced calpain-dependent
      death pathway in human neuroblastoma SH-SY5Y cultured cells.
AB  - Methamphetamine (METH) is a potent psychostimulant drug that may cause neuronal
      cell degeneration. The underlying mechanisms of METH-induced neuronal toxicity
      remains poorly understood. In this study, we investigated an important role of
      calpain-dependent cascades in methamphetamine-induced toxicity in human
      dopaminergic neuroblastoma SH-SY5Y cultured cell lines. In addition, the
      protective effect of melatonin against METH-induced calpain-dependent death
      pathway was also investigated. The results of this study show that METH
      significantly decreased cell viability and tyrosine hydroxylase phosphorylation
      in SH-SY5Y cultured cells. Melatonin reversed the toxic effect of METH by
      inducing cell viability. In addition, melatonin was able to restore the reduction
      in mitochondrial function and phosphorylation of tyrosine hydroxylase in SH-SY5Y
      treated cells. An induction of calpain expression and activity but a reduction of
      calpain inhibitor (calpastatin) protein levels were observed in SH-SY5Y cells
      treated with METH but these effects were diminished by melatonin. These results
      implicated calpain-dependent death pathways in the processes of METH-induced
      toxicity and also indicated that melatonin has the capacity to reverse this toxic
      effect in SH-SY5Y cultured cells.

PMID- 20050991
TI  - Targeting school-based dental sealant programs: who is at "higher risk"?
AB  - OBJECTIVES: To assess the effect of various school-level Free and Reduced Price
      Meal Program (FRPMP) enrollment-based risk thresholds on the ability of school
      based sealant programs (S-BSPs) to reach higher risk children. METHODS: We used
      data from a statewide third grade oral health survey to compare: a) prevalence of
      dental caries for higher-risk children, using three different sets of child risk
      criteria based on social determinants; and b) dental caries and other access
      related indicators for children at higher-risk schools based on four FRPMP-based
      thresholds (> or = 60 percent of children FRPMP-enrolled, > or = 50 percent, > or
      = 40 percent, > or = 30 percent). In addition, we used school enrollment and
      FRPMP enrollment data to compare the percentages of eligible schools and of
      higher-risk children resulting from the various thresholds. RESULTS: The
      prevalence of caries experiences and untreated caries were not significantly
      different for higher risk children categorized by the respective child caries
      risk criteria. Regardless of school-level risk threshold, children at higher risk
      schools were more likely to have caries experience, untreated caries, and no
      recent dental visit and less likely to have private dental insurance than
      children at lower risk schools. For these measures, children at higher risk
      schools were similar to each other regardless of risk threshold and were similar
      to higher risk children at all schools. The number of additional higher risk
      children per additional higher risk school showed a large decline between the 40
      49 percent and 30-39 percent FRPMP enrollment tiers. CONCLUSIONS: Targeting
      higher risk schools to reach higher risk children is a practical and effective
      approach for increasing sealant prevalence through S-BSPs.

PMID- 20050992
TI  - Reaction of sleepiness indicators to partial sleep deprivation, time of day and
      time on task in a driving simulator--the DROWSI project.
AB  - Studies of driving and sleepiness indicators have mainly focused on prior sleep
      reduction. The present study sought to identify sleepiness indicators responsive
      to several potential regulators of sleepiness: sleep loss, time of day (TOD) and
      time on task (TOT) during simulator driving. Thirteen subjects drove a high
      fidelity moving base simulator in six 1-h sessions across a 24-h period, after
      normal sleep duration (8 h) and after partial sleep deprivation (PSD; 4 h). The
      results showed clear main effects of TOD (night) and TOT but not for PSD,
      although the latter strongly interacted with TOD. The most sensitive variable was
      subjective sleepiness, the standard deviation of lateral position (SDLAT) and
      measures of eye closure [duration, speed (slow), amplitude (low)]. Measures of
      electroencephalography and line crossings (LCs) showed only modest responses. For
      most variables individual differences vastly exceeded those of the fixed effects,
      except for subjective sleepiness and SDLAT. In a multiple regression analysis,
      SDLAT, amplitude/peak eye-lid closing velocity and blink duration predicted
      subjective sleepiness bouts with a sensitivity and specificity of about 70%, but
      were mutually redundant. The prediction of LCs gave considerably weaker, but
      similar results. In summary, SDLAT and eye closure variables could be candidates
      for use in sleepiness-monitoring devices. However, individual differences are
      considerable and there is need for research on how to identify and predict
      individual differences in susceptibility to sleepiness.

PMID- 20050993
TI  - Sleep history affects task acquisition during subsequent sleep restriction and
      recovery.
AB  - The aim of the present study was to examine if sleep amount prior to sleep
      restriction mediated subsequent task acquisition on serial addition/subtraction
      and reaction time (RT) sub-tasks of the Automated Neuropsychological Assessment
      Metric. Eleven males and 13 females [mean (SD) age = 25 (6.5) years] were
      assigned to either an Extended [10 h time in bed (TIB)] (n = 12) or Habitual
      [Mean (SD) = 7.09 (0.7)] (n = 12) sleep group for 1 week followed by one baseline
      night, seven sleep restriction nights (3 h TIB) and five recovery nights (8 h
      TIB). Throughout baseline, restriction and recovery, mathematical and serial RT
      tasks were administered hourly each day (08:00-18:00 h). Math and serial RT
      throughput for each task (speed x accuracy product) was analysed using a mixed
      model anova with fixed effects for sleep group, day and time-of-day followed by
      post hoc t-tests (Bonferroni correction). Math throughput improved for both
      groups during sleep restriction, but more so compared with baseline for the prior
      sleep Extended group versus the Habitual group during recovery. In sum, 1 week of
      sleep extension improved resilience during subsequent sleep restriction and
      facilitated task acquisition during recovery, demonstrating that nightly sleep
      duration exerts long-term (days, weeks) effects.

PMID- 20050994
TI  - Sleep deprivation impairs spatial working memory and reduces hippocampal AMPA
      receptor phosphorylation.
AB  - Sleep is important for brain function and cognitive performance. Sleep
      deprivation (SD) may affect subsequent learning capacity and ability to form new
      memories, particularly in the case of hippocampus-dependent tasks. In the present
      study we examined whether SD for 6 or 12 h during the normal resting phase prior
      to learning affects hippocampus-dependent working memory in mice. In addition, we
      determined effects of SD on hippocampal glutamate alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptors and their regulatory pathways, which
      are crucially involved in working memory. After 12 h SD, but not yet after 6 h,
      spatial working memory in a novel arm recognition task was significantly
      impaired. This deficit was not likely due to stress as corticosterone levels
      after SD were not significantly different between groups. In parallel with the
      change in cognitive function, we found that 12 h SD significantly reduced
      hippocampal AMPA receptor phosphorylation at the GluR1-S845 site, which is
      important for incorporation of the receptors into the membrane. SD did not affect
      protein levels of cyclic-AMP-dependent protein kinase A (PKA) or phosphatase
      calcineurin (CaN), which regulate GluR1 phosphorylation. However, SD did reduce
      the expression of the scaffolding molecule A-kinase anchoring protein 150
      (AKAP150), which binds and partly controls the actions of PKA and CaN. In
      conclusion, a relatively short SD during the normal resting phase may affect
      spatial working memory in mice by reducing hippocampal AMPA receptor function
      through a change in AKAP150 levels. Together, these findings provide further
      insight into the possible mechanism of SD-induced hippocampal dysfunction and
      memory impairment.

PMID- 20050995
TI  - The sleep of children with attention deficit hyperactivity disorder on and off
      methylphenidate: a matched case-control study.
AB  - In the present study, we assessed the effects of regular use of methylphenidate
      medication in children diagnosed with attention deficit hyperactivity disorder
      (ADHD) on sleep timing, duration and sleep architecture. Twenty-seven children
      aged 6-12 years meeting diagnostic criteria for Diagnostic and Statistical Manual
      version IV ADHD and 27 control children matched for age (+/-3 months) and gender.
      Two nights of standard polysomnographic (PSG) recordings were conducted. ADHD
      children were allocated randomly to an on- or 48 h off-methylphenidate protocol
      for first or second recordings. Control children's recordings were matched for
      night, but no medication was used. Mixed modelling was employed in the analyses
      so that the full data set was used to determine the degree of medication effects.
      Methylphenidate in ADHD children prolonged sleep onset by an average of 29 min
      [confidence interval (CI) 11.6, 46.7], reduced sleep efficiency by 6.5% (CI 2.6,
      10.3) and shortened sleep by 1.2 h (CI 0.65, 1.9). Arousal indices were
      preserved. Relative amounts of stages 1, 2 and slow wave sleep were unchanged by
      medication. Rapid eye movement sleep was reduced (-2.4%) on the medication night,
      an effect that became non-significant when control data were incorporated in the
      analyses. PSG data from ADHD children off-medication were similar to control
      data. Our findings suggest that methylphenidate reduces sleep quantity but does
      not alter sleep architecture in children diagnosed with ADHD. An adequate amount
      of sleep is integral to good daytime functioning, thus the sleep side effects of
      methylphenidate may affect adversely the daytime symptoms the drug is targeted to
      control.

PMID- 20050996
TI  - Perception of experimental pain is reduced after provoked waking from rapid eye
      movement sleep.
AB  - Patients with chronic pain often complain of pain when they wake at night, but
      the accuracy of their perception of the pain after waking at night is unknown.
      While cognitive functions are reduced for a short time after waking from sleep, a
      situation known as sleep inertia, it is unclear how sleep inertia may affect the
      perception of pain. We investigated the effects of sleep inertia on the
      perception of experimentally induced pain. Fourteen male volunteers were exposed
      to a randomized thermal heat stimulus of 43.1 degrees C 'hot' and 46.5 degrees C
      'hurting' during provoked waking from Stage 2 sleep, slow wave sleep and rapid
      eye movement (REM) sleep. Subjects rated their pain on awakening on a Visual
      Analogue Scale at 30 s after awakening and each minute thereafter for 5 min. We
      found no change in pain perception over the 5-min period irrespective of
      temperature used or sleep stage. However, perceived pain when awoken abruptly
      from REM sleep was significantly lower than the awake score for both the hot (P =
      0.0069) and hurting (P = 0.0025) temperatures. Pain perception when woken from
      Stage 2 sleep or slow wave sleep was not significantly different from perception
      when awake. Our findings indicate that sleep inertia reduces pain perception when
      awoken abruptly from REM. This suggests that patients who wake up in pain either
      perceive accurately the pain they are experiencing, or at worst underestimate the
      level of pain if woken from REM sleep.

PMID- 20050997
TI  - Cardiorespiratory response to spontaneous cortical arousals during stage 2 and
      rapid eye movement sleep in healthy children.
AB  - Arousal from sleep is associated with transient and abrupt cardiorespiratory
      changes, and elevated arousals associated with sleep disorders may trigger
      adverse cardiovascular sequela. In this paper, we provide the first data in
      children on cardiorespiratory responses to cortical arousal. Heart rate and
      ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep
      were investigated in 40 normal, healthy Caucasian children (age: 7.7 +/- 2.6
      years; body mass index z-score: 0.30 +/- 0.8). All children underwent overnight
      polysomnography studies. Cortical arousals were scored according to standard
      criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to
      cortical arousal onset. Breathing rates were quantified three breaths before and
      after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R
      R interval shortening of about 15%, independent of age and gender. The R-R
      interval shortening initiated at least 3 s before the cortical arousal onset. The
      breathing interval immediately after cortical arousal onset was significantly
      shortened (P < 0.001). In conclusion, cortical arousals in children are
      associated with an increase in breathing rate and significant heart rate
      accelerations, which typically precede the cortical arousal onset.

PMID- 20050998
TI  - Anti-PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis:
      the role of non-drug risk factors and evidence for a stoichiometry-based model of
      immunization.
AB  - BACKGROUND: Heparin-induced thrombocytopenia is an antibody-mediated disorder
      exhibiting variable frequency in different clinical settings. Antibodies
      recognize PF4/heparin complexes formed at optimal stoichiometric molar ratios.
      OBJECTIVE: To identify clinical factors influencing risk of anti-PF4/heparin
      immunization. PATIENTS/METHODS: We performed observational studies and
      exploratory analyses of the frequency of anti-PF4/heparin antibody formation in
      6324 patients who received enoxaparin or fondaparinux in four randomized
      controlled trials of postorthopedic surgery thromboprophylaxis. Variables
      included surgery type (knee vs. hip), timing of first anticoagulant dose (pre-
      vs. postsurgery), circumstances of surgery (elective vs. hip fracture),
      anticoagulant (enoxaparin vs. fondaparinux) and body-mass index (BMI). We applied
      a stoichiometry-based model that predicts immunization risk based on expected
      differences in PF4/anticoagulant ratios in different settings, and specifically
      used this model to predict the effect of increasing BMI quartiles upon relative
      risk (RR) of immunization for fondaparinux vs. enoxaparin. RESULTS: Anti
      PF4/heparin immunization was more frequent after knee vs. hip surgery
      (particularly for enoxaparin), and when enoxaparin was given post- rather than
      pre-elective surgery; however, the opposite occurred with hip fracture surgery,
      that is, antibody formation was more frequent when enoxaparin or fondaparinux was
      given presurgery. The RR of immunization for fondaparinux vs. enoxaparin
      decreased significantly for increasing BMI quartiles, an effect predominantly
      because of increasing immunization with enoxaparin at increasing BMI quartiles.
      CONCLUSIONS: Several non-drug factors--including type and circumstances of
      surgery, timing of first anticoagulant dose and BMI--influence risk of anti
      PF4/heparin antibody formation, consistent with a stoichiometry-based
      immunization model of PF4 and anticoagulant ratios occurring during the early
      peri-operative period.

PMID- 20050999
TI  - Re-exposure to heparin in uremic patients requiring hemodialysis with heparin
      induced thrombocytopenia.

PMID- 20051000
TI  - Uveal inflammation in septic newborn foals.
AB  - BACKGROUND: Septicemia in humans is described as a leading cause of uveitis,
      which eventually can induce blindness. HYPOTHESIS/OBJECTIVES: Uveal inflammatory
      findings could be related to sepsis severity in newborn foals and might be used
      as an indirect indicator for survival. ANIMALS: Seventy-four septic foals, 54
      nonseptic foals, and 42 healthy foals. METHODS: Prospective observational
      clinical study. A detailed blinded, ophthalmic examination was performed by
      boarded ophthalmologists on all admitted newborn foals. Foals were grouped as
      septic (when blood culture resulted positive or the sepsis score was > or =14),
      nonseptic, and controls. Based on blood culture results, the septic group was
      subdivided into bacteremic and nonbacteremic foals. RESULTS: Blood culture was
      performed in 62/74 septic foals, from which 35 (56%) were bacteremic and 27 (44%)
      were non-bacteremic. Anterior uveitis was diagnosed in a significantly (P < .005)
      higher number of septic/bacteremic foals (14/35, 40%) than in
      septic/nonbacteremic foals (5/27, 19%), nonseptic foals (4/54, 7%), and control
      foals (0%). Anterior chamber fibrin was only observed in 4/14 (29%)
      septic/bacteremic foals with anterior uveitis. Anterior uveitis was also
      associated with posterior uveitis in 6/35 (19%) septic/bacteremic foals. The
      diagnosis of uveitis was related to nonsurvival (P = .001, odds ratio = 6.2, 95%
      confidence interval = 2.1-18.2). CONCLUSIONS AND CLINICAL IMPORTANCE: Anterior
      uveitis is highly prevalent in septic newborn foals, especially in those with a
      positive blood culture, and it should be considered as a survival prognostic
      factor.

PMID- 20051001
TI  - Tracheal collapse and bronchomalacia in dogs: 58 cases (7 /2001-1 /2008).
AB  - BACKGROUND: Tracheobronchomalacia is diagnosed in people by documentation of a
      reduction in airway diameter during bronchoscopy. While tracheal collapse in the
      dog has been well described in the literature, little information is available on
      bronchomalacia in the dog. HYPOTHESES: Bronchomalacia is common in dogs with
      tracheal collapse, is associated with inflammatory airway disease, and is poorly
      documented radiographically. ANIMALS: One hundred and fifteen dogs admitted for
      evaluation for respiratory disease and examined by bronchoscopy. METHODS: Case
      controlled, observational study. Dogs examined and having a bronchoscopic
      procedure performed by a single operator were separated into groups with and
      without visually identified airway collapse. Clinical parameters and
      bronchoalveolar lavage findings were compared between groups. Radiographs were
      reviewed in masked fashion to assess the sensitivity and specificity for
      detection of bronchomalacia. RESULTS: Tracheobronchomalacia was documented in 50%
      of dogs examined, with tracheal collapse in 21% and bronchomalacia in 47%. In
      dogs with bronchomalacia, collapse of the right middle (59%) and left cranial
      (52%) lung lobes was identified most commonly. Dogs with bronchomalacia were
      significantly more likely to display normal airway cytology and to have mitral
      regurgitation and cardiomegaly than dogs without airway collapse (P < .05).
      Radiographs were insensitive for detection of airway collapse. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Bronchomalacia was identified more commonly than tracheal
      collapse in this population of dogs, and documentation required bronchoscopy.
      This study could not confirm a role for airway inflammation in bronchomalacia,
      and further studies are required to determine the role of cardiomegaly in the
      disorder.

PMID- 20051002
TI  - Randomized clinical trial of long-acting oxytetracycline, foot trimming, and
      flunixine meglumine on time to recovery in sheep with footrot.
AB  - BACKGROUND: Internationally, foot trimming is used by most farmers, and
      parenteral antibacterials by some, to treat sheep with footrot. Nonsteroidal anti
      inflammatory drugs (NSAID) are sometimes used. No clinical trials have compared
      these treatments. OBJECTIVES: To investigate the above treatments on time to
      recovery from lameness and foot lesions in sheep with footrot. ANIMALS: Fifty
      three sheep with footrot on a commercial farm in England. METHODS: In a
      randomized factorial design, the sheep were allocated to 6 treatment groups. The
      treatments were oxytetracycline spray to all sheep (positive control) and one or
      more of parenteral administration of long-acting oxytetracycline, flunixine
      meglumine, and foot trimming on day 1 or 6 of diagnosis. Follow-up was for 15
      days. Time to recovery from lameness and lesions was investigated with discrete
      time survival models. RESULTS: There was significant association (P < .05)
      between recovery from lameness and lesions. Sheep receiving antibacterials
      parenterally recovered faster from lameness (odds ratio [OR]: 4.92 [1.20-20.10])
      and lesions (OR: 5.11 [1.16-22.4]) than positive controls, whereas sheep foot
      trimmed on day 1 (lameness-OR: 0.05 [0.005-0.51]; lesions-OR: 0.06 [0.008-0.45])
      or day 6 of diagnosis (lameness OR: 0.07 [0.01-0.72]; lesions OR: 0.07 [0.01
      04).56]) recovered more slowly than positive controls. NSAID had no significant
      effect on recovery. CONCLUSIONS AND CLINICAL IMPORTANCE: If foot trimming on day
      1 or 6 of diagnosis was stopped and parenteral antibacterials were used, then
      over 1 million sheep/annum lame with footrot in the United Kingdom would recover
      more rapidly with benefits to productivity. Globally, this figure would be much
      higher.

PMID- 20051003
TI  - Canine sterile nodular panniculitis: a retrospective study of 14 cases.
AB  - BACKGROUND: Sterile nodular panniculitis (SNP) is an uncommon inflammatory
      condition of subcutaneous fat that can be idiopathic, but has also been
      associated with underlying conditions such as pancreatic disease or systemic
      lupus erythematosus (SLE). The pathogenesis and clinical course of the condition
      are not well understood. OBJECTIVES: To retrospectively review cases of SNP
      associated with systemic signs, concurrent disease, or both and characterize the
      clinical, laboratory, imaging, and histopathologic findings, treatment, and
      response to treatment. ANIMALS: Fourteen dogs with histologically confirmed SNP
      diagnosed between 1996 and 2008. METHODS: Retrospective study. RESULTS: Skin
      lesions were ulcerated or draining nodules in 9 dogs and nonulcerative
      subcutaneous nodules in 5. Most dogs had systemic signs, such as fever,
      inappetence, lethargy, and multiple lesions. Common clinicopathologic findings
      included neutrophilia with or without left shift, increased alkaline phosphatase
      activity, mild hypoglycemia, hypoalbuminemia, and proteinuria. Concurrent
      diseases included pancreatic disease, SLE, rheumatoid arthritis, polyarthritis,
      lymphoplasmacytic colitis, and hepatic disease. Dogs responded to
      immunosuppressive doses of corticosteroids when administered. Prognosis for
      recovery was related to the underlying disease process. CONCLUSIONS AND CLINICAL
      IMPORTANCE: SNP is not a single disease. Rather, it is a cutaneous marker of
      systemic disease in many cases. After thorough evaluation for concurrent disease
      and infectious causes, immunosuppressive treatment is often effective.

PMID- 20051004
TI  - Echocardiographic assessment of hemodynamic changes produced by two methods of
      inducing fluid deficit in dogs.
AB  - BACKGROUND: Hydration status is important to the cardiovascular system because of
      its effects on preload. Decreased preload can alter echocardiographic
      measurements of systolic and diastolic function, potentially confounding
      interpretation of results. HYPOTHESIS/OBJECTIVES: Mild fluid deficits are
      associated with measurable echocardiographic changes that are validated by
      physical and biochemical markers of decreased intravascular volume. ANIMALS:
      Twenty-five healthy staff/student-owned dogs with no evidence of cardiac or renal
      disease. METHODS: Prospective, interventional laboratory study. Dogs were
      randomly assigned to water deprivation (WD) alone for 8 hours (n = 13) or to
      furosemide treatment (FTx, 2.5mg/kg IV) followed by WD for 8 hours (n = 12).
      Echocardiograms, biochemical sampling, and physical parameters were measured at
      baseline, and after 4 and 8 hours. RESULTS: Both protocols induced fluid deficit
      as indicated by significant (P < .00001) decreases in weight at 4 hours (WD,
      1.1%; FTx, 3.7%) and 8 hours (WD, 2.7%; FTx, 4.5%). Furosemide significantly
      decreased left ventricular end-diastolic volume (54.3 +/- 19.3-42.1 +/- 17.3 mL,
      P < .0001), cardiac index (4.2 +/- 1.1-2.9 +/- 0.9 L/min/M2, P < .0001), and
      mitral valve E wave velocity (0.79 +/- 0.2-0.66 +/- 0.2 m/s, P = .0004). These
      changes were accompanied by significant increases in blood urea nitrogen
      concentration (13.8 +/- 2.6-14.8 +/- 2.7 mg/dL, P = .04), vasopressin
      concentration (1.4 +/- 1.2-3.3 +/- 1.9 pg/mL, P = .045), and PCV (49.8 +/- 4.5
      53.2 +/- 6.5%, P = .006). Effects of water deprivation alone were similar, but
      less pronounced. CONCLUSIONS AND CLINICAL IMPORTANCE: Mild fluid deficits have
      measurable hemodynamic effects in dogs. Hydration status should be considered
      when evaluating cardiac function by echocardiogram.

PMID- 20051005
TI  - Comparison of oral prednisone and prednisone combined with metronidazole for
      induction therapy of canine inflammatory bowel disease: a randomized-controlled
      trial.
AB  - BACKGROUND: Although prednisone and metronidazole are commonly used to treat
      canine inflammatory bowel disease (IBD), no randomized-controlled trials have
      been performed. HYPOTHESIS: Combination drug therapy with prednisone and
      metronidazole will be more effective than prednisone alone for treatment of
      canine IBD. Reduction in disease severity will be accompanied by decreased canine
      IBD activity index (CIBDAI) scores and serum C-reactive protein (CRP)
      concentrations. ANIMALS: Fifty-four pet dogs diagnosed with IBD of varying
      severity. METHODS: Dogs were randomized to receive oral prednisone (1 mg/kg; n =
      25) or prednisone and metronidazole (10 mg/kg; n = 29) twice daily for 21 days.
      Clinical (CIBDAI) scores and serum CRP were determined at diagnosis and after 21
      days of drug therapy. The primary efficacy measure was remission at 21 days,
      defined as a 75% or greater reduction in baseline CIBDAI score. RESULTS:
      Differences between treatments in the rate of remission (both exceeding 80%) or
      the magnitude of its change over time were not observed. CRP concentrations in
      prednisone-treated dogs were increased because of many dogs having active
      disease. Both treatments reduced CRP in comparison with pretreatment
      concentrations. An interaction between CIBDAI and CRP was identified in 42 of 54
      dogs (78%), whereas 8 of 54 dogs (15%) showed disagreement between these indices.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Prednisone is as effective as combined
      treatment with prednisone and metronidazole for induction therapy of canine IBD.
      CRP may be normal or increased in dogs with IBD and may be useful in assessing
      the response of individual dogs to treatment along with changes in the CIBDAI.

PMID- 20051007
TI  - Spontaneous clearance and the beneficial impact of treatment on clearance during
      recent hepatitis C virus infection.

PMID- 20051006
TI  - Hepatitis C virus modulates human monocyte-derived dendritic cells.
AB  - This study is to examine the monocyte-derived dendritic cell (DC) response to
      hepatitis C virus (HCV) in a cell culture system. Adherence-derived DCs were
      incubated with various titres of JFH-1 (HCV genotype 2a), generated from
      transfected Huh 7.5 cells or co-incubated with Newcastle disease virus (NDV).
      Infection and the type 1 interferon (IFN) response were assessed by real-time
      reverse transcriptase-polymerase chain reaction, morphology by light microscopy
      and immunophenotype by flow cytometry. Our data demonstrated no viral replication
      or particle release from DC after HCV infection. Morphologically, monocytes
      showed a tendency to shift to immature DCs when cultured with HCV, when compared
      with control monocytes. This shift was confirmed by flow cytometry and appeared
      to be related to viral titres. There was also an increase in immature DC numbers.
      HCV infection induced IFNbeta expression in DCs, and the amount seemed to be
      inversely correlated with viral titres indicating that HCV has the capacity to
      negatively regulate such cells. However, IFNalpha does not appear to be affected
      by direct contact with the virus. A strong IFNbeta signal induced by NDV in DC
      was substantially diminished by HCV. HCV negatively affects the maturation of DCs
      and suppresses the type 1 IFN response of DC. Our results suggest a mechanism of
      viral evasion of host immunity.

PMID- 20051008
TI  - Persistent and transient hepatitis B virus (HBV) infections in children born to
      HBV-infected mothers despite active and passive vaccination.
AB  - Combined passive and active immunization for newborns very effectively prevents
      perinatal hepatitis B virus (HBV) infections. In the Netherlands, babies born to
      hepatitis B surface antigen (HBsAg)-positive women receive passive immunization
      with hepatitis B and at least three active HBsAg vaccinations. Serological
      testing for the presence of HBV markers was offered for all infants born to HBsAg
      positive mothers between January 2003 and July 2007, after completion of their
      vaccination schedule. About 75% of the infants (n = 1743) completed their HB
      vaccination schedule and participated in the serologic evaluation. Twelve of them
      (0.7%) were found to be HBV infected. Furthermore, we identified three older
      children with high levels of anti-HBc, anti-HBs and anti-HBe, while they were
      HBsAg and HBV DNA negative. This serologic profile is evidence for a resolved HBV
      infection. In the group of older children (1.5-5 years of age, n = 728), about
      half of the HBV-infected children (3 of 7) had already cleared their infection at
      the time of sampling. For a proper evaluation of the efficacy of a new
      intervention programme to prevent vertical HBV transmission, it is also important
      to analyse the HBV markers in serum collected when the children are older than
      1.5 years. In a programmatic setting, all children born to HBV-infected mothers
      should be tested not only for the level of anti-HBs but also for the absence of
      HBsAg, because 2 of the 12 HBV-infected children (17%) had a high level of anti
      HBs.

PMID- 20051009
TI  - Population genetics of Mioscirtus wagneri, a grasshopper showing a highly
      fragmented distribution.
AB  - The genetic consequences of population fragmentation and isolation are major
      issues in conservation biology. In this study we analyse the genetic variability
      and structure of the Iberian populations of Mioscirtus wagneri, a specialized
      grasshopper exclusively inhabiting highly fragmented hypersaline low grounds. For
      this purpose we have used seven species-specific microsatellite markers to type
      478 individuals from 24 localities and obtain accurate estimates of their genetic
      variability. Genetic diversity was relatively low and we detected genetic
      signatures suggesting that certain populations of M. wagneri have probably passed
      through severe demographic bottlenecks. We have found that the populations of
      this grasshopper show a strong genetic structure even at small geographical
      scales, indicating that they mostly behave as isolated populations with low
      levels of gene flow among them. Thus, several populations can be regarded as
      independent and genetically differentiated units which require adequate
      conservation strategies to avoid eventual extinctions that in highly isolated
      localities are not likely to be compensated for with the arrival of immigrants
      from neighbouring populations. Overall, our results show that these populations
      probably represent the 'fragments' of a formerly more widespread population and
      highlight the importance of protecting Iberian hypersaline environments due to
      the high number of rare and endangered species they sustain.

PMID- 20051010
TI  - Genetic structure in the Mediterranean seagrass Posidonia oceanica: disentangling
      past vicariance events from contemporary patterns of gene flow.
AB  - The Mediterranean Sea is a two-basin system, with the boundary zone restricted to
      the Strait of Sicily and the narrow Strait of Messina. Two main population groups
      are recognized in the Mediterranean endemic seagrass Posidonia oceanica,
      corresponding to the Western and the Eastern basins. To address the nature of the
      East-West cleavage in P. oceanica, the main aims of this study were: (i) to
      define the genetic structure within the potential contact zone (i.e. the Strait
      of Sicily) and clarify the extent of gene flow between the two population groups,
      and (ii) to investigate the role of present water circulation patterns vs. past
      evolutionary events on the observed genetic pattern. To achieve these goals, we
      utilized SSR markers and we simulated, with respect to current regime, the
      possible present-day dispersal pattern of Posidonia floating fruits using 28-day
      numerical Lagrangian trajectories. The results obtained confirm the presence of
      the two main population groups, without any indices of reproductive isolation,
      with the break zone located at the level of the Southern tip of Calabria. The
      populations in the Strait of Sicily showed higher affinity with Western than with
      Eastern populations. This pattern of genetic structure probably reflects
      historical avenues of recolonization from relict glacial areas and past
      vicariance events, but seems to persist as a result of the low connectivity among
      populations via marine currents, as suggested by our dispersal simulation
      analysis.

PMID- 20051011
TI  - Nuclear gene phylogeography reveals the historical legacy of an ancient inland
      sea on lineages of the western pond turtle, Emys marmorata in California.
AB  - The historical biogeography of California's taxa has been the focus of extensive
      research effort. The western pond turtle (Emys marmorata) is an example of a wide
      ranging taxon that spans several well-known California diversity hotspots. Using
      a dataset comprised of one mitochondrial and five nuclear loci, we elucidate the
      major biogeographic patterns of the western pond turtle across the California
      landscape. By employing a combination of phylogenetic and network-based
      approaches, we recovered a relatively ancient (c. 2-8 Ma) north/south split among
      populations of E. marmorata and find an area of intergradation centred in the
      Central Coast Ranges of California. In addition, discordant mitochondrial/nuclear
      genetic patterns suggest subsequent gene flow from northern populations and from
      San Joaquin Valley populations into the Central Coast Ranges after the Pliocene
      Pleistocene marine embayment of the Great Central Valley subsided. Our results
      emphasize the utility of nuclear DNA phylogeography for recovering the impact of
      relatively ancient biogeographic events, and suggest that the Central Coast
      Ranges of California have played a major role in the geographic structuring of
      the western pond turtle, and possibly other co-distributed taxa.

PMID- 20051012
TI  - Invasive aspergillosis caused by Aspergillus terreus in a living donor liver
      transplant recipient successfully treated by caspofungin.
AB  - Invasive aspergillosis is one of the most severe complications after liver
      transplantation characterised by early dissemination of disease and high
      mortality. Recent data show that the prognosis is diminishing even further when
      Aspergillus terreus, a strain resistant to standard treatment with amphotericin,
      is isolated. We report a high risk liver transplant recipient with multiple co
      morbidities including renal failure and allograft dysfunction in whom pulmonary
      aspergillosis due to A. terreus was successfully treated by the echinocandin
      antifungal agent caspofungin.

PMID- 20051013
TI  - Differences in patient risk factors and source of candidaemia caused by Candida
      albicans and Candida glabrata.
AB  - There is an increasing frequency of candidaemia caused by Candida glabrata which
      has decreased in vitro susceptibility to fluconazole. Differences in risk factors
      for candidaemia caused by C. glabrata and C. albicans have not been formally
      evaluated in a diverse patient group. We performed a retrospective study of adult
      inpatients from January 1, 2003 to April 30, 2008 with C. glabrata and C.
      albicans candidaemia at a single tertiary care centre in Detroit, Michigan to
      evaluate for differences in risk factors and presumed source of infection in
      these groups. Patients' underlying conditions, risk factors and source of
      infection (probable or definite) were compared. Among 119 patients, 80 (67.2%)
      were C. albicans and 39 (32.8%) C. glabrata. Using logistic regression analysis,
      patients with C. glabrata infection were more likely to have diabetes mellitus
      (OR 2.43; 95% CI, 1.06-5.54) and abdominal source of infection (OR 4.53, 95% CI,
      1.72-11.92). Mortality rates in the two groups were similar. Patients with C.
      glabrata candidaemia are more likely to be diabetic and have an abdominal source
      of infection compared with patients with C. albicans.

PMID- 20051014
TI  - Pseudopolyneuritic form of ALS revisited: clinical and pathological
      heterogeneity.
AB  - Pseudopolyneuritic form of ALS is a subtype of ALS characterized by distal
      weakness of the unilateral lower limb and absence of Achilles tendon reflex (ATR)
      at disease onset. Recognition of this form of ALS is important for clinicians
      because the combination of distal weakness of the lower limb and absence of ATR
      usually suggests peripheral neuropathy. We reviewed the clinical records of 42
      autopsy-proven sporadic ALS cases and found three cases that showed onset of
      weakness of the unilateral lower limb with distal dominance and absence of ATR.
      The disease duration in the three cases was 2, 3 and 19 years, respectively. The
      clinical features of the patient with a course of 19 years had been restricted to
      lower motor neuron signs. Histopathologically, consistent findings in the three
      cases were severe motor neuron loss throughout the whole spinal cord, with
      relative preservation of the hypoglossal nucleus. Reflecting this finding, TDP-43
      positive neuronal cytoplasmic inclusions in the spinal cord were sparse in two
      cases, and absent in a third. In the patient showing a clinical course of 19
      years, mild corticospinal tract degeneration appeared to correspond to the
      absence of upper motor neuron signs and prolonged disease duration. In this case
      only, Bunina bodies were not demonstrated. In this study, we clarified the
      clinical and pathological heterogeneity of this form of ALS.

PMID- 20051015
TI  - Pinealoblastoma with prominent retinoblastic differentiation: an unusual case in
      an adult.
AB  - We present an extremely rare case of pinealoblastoma with retinoblastic
      differentiation in a 32-year-old woman who presented with a history of
      intermittent headache of 2 years duration and diminution of vision for 2 months
      which eventually lead to total loss of vision. The fundus examination showed
      bilateral secondary optic atrophy. She did not have any previous history of
      retinoblastoma. The family history was non-contributory. Paraffin section of the
      tumor showed a primitive neuroectodermal tumor with numerous Flexner
      Wintersteiner rosettes and the tumor cells were strongly positive for
      synaptophysin and negative for GFAP, S-100 protein and epithelial membrane
      antigen. This is the first case in the literature of a sporadic case of
      pinealoblastoma with prominent retinoblastic differentiation as evidenced
      histomorphologically by the presence of numerous Flexner-Wintersteiner rosettes
      in an adult female.

PMID- 20051016
TI  - Cytopathy of an infiltrating monocyte lineage during the early phase of infection
      with murinecoronavirus in the brain.
AB  - Viral spread during the early stages after infection was compared between a
      highly neurovirulent mouse hepatitis virus (MHV), JHMV cl-2 strain (cl-2), and
      its low-virulent mutant, soluble-receptor-resistant (srr)7. The infection of
      cells with srr7 (soluble-receptor-resistant mutant 7) is dependent on a known MHV
      receptor (MHVR), carcinoembryonic cell adhesion molecule 1a, whereas cl-2 shows
      MHVR-independent infection. Initial viral antigens were detected between 12 and
      24 h post-inoculation (p.i) in the infiltrating cells that appeared in the
      subarachnoidal space of mouse brains infected with viruses. There were no
      significant differences in the intensity or spread of viral antigens in the
      inflammatory cells between the two viruses. However, 48 h after infection with cl
      2, viral antigen-positive cells in the grey matter with the shape of neurons,
      which do not express MHVR, were detected, while srr7 infection was observed
      primarily in the white matter. Some of the viral antigen-positive inflammatory
      cells found in the subarachnoidal space during the early phase of infection
      reacted with anti-F4/80 or anti-CD11b monoclonal antibodies. Syncytial giant
      cells (SGCs) expressing viral and CD11b antigens were also detected among these
      inflammatory cells. These antigen-positive cells appeared in the subarachnoidal
      space prior to viral antigen spread into the brain parenchyma, indicating that
      viral encephalitis starts with the infection of infiltrating monocytes which
      express MHVR. Furthermore, the observation indicates that viral infection has
      cytopathic effects on the monocyte lineage, which plays a critical role in innate
      immunity, leading to the rapid spread of viruses during the early stage of
      infection.

PMID- 20051017
TI  - Primary glioblastomas with and without EGFR amplification: relationship to
      genetic alterations and clinicopathological features.
AB  - Glioblastomas express a notable heterogeneity in both the histological and cell
      patterns with glial astrocytic differentiation. Primary glioblastoma, which is
      the most frequent presentation (90-95%), occurs mainly in older patients and
      arises de novo, without any clinical or histological evidence of a less malignant
      precursor lesion. EGFR amplification has been identified as a genetic hallmark of
      primary glioblastomas and occurs in 40-60% of cases. However, there exist primary
      glioblastomas without EGFR amplification/overexpression. The purpose of this
      study was to stabilize the association between cases with and without EGFR gene
      amplification with clinical and genetic parameters in 45 cases of primary
      glioblastomas. EGFR amplification was observed in 24 cases (53%), while in the
      remaining 21 cases (47%) this alteration was not displayed. And whereas EGFR was
      overexpressed in 79% of cases with EGFR amplification, only 33% of the cases
      without EGFR amplification showed overexpression. The amplification of EGFR was
      associated with amplifications in MDM2 and CDK4 and a higher percentage of cases
      with promoter methylation of INK4a. Only one case of glioblastoma with EGFR
      amplification presented TP53 mutation simultaneously. Seven remaining cases with
      TP53 mutations were glioblastomas without EGFR amplification. The INK4a, INK4b
      and ARF deletions were similar in the two groups. Primary glioblastomas with and
      without EGFR amplification did not show any significant differences in average
      survival. The genetic studies suggest the existence of molecular subtypes within
      primary glioblastoma that may, when fully defined, contribute toward the
      development of drugs that specifically target tumors with divergent genetic
      profiles.

PMID- 20051018
TI  - Intraventricular pleomorphic xanthoastrocytoma with anaplastic features.
AB  - Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic tumor that usually
      occurs in the superficial cerebral hemispheres of children and young adults and
      has a relatively favorable prognosis. We report an unusual case of
      supratentorial, intraventricular tumor in a 52-year-old man. The tumor was
      composed of pleomorphic cells, including giant cells, most of which were
      multinucleated, and small cells. In addition, frequent xanthic changes in the
      cytoplasm of the tumor cells, and widespread reticulin deposits and lymphocytic
      infiltrates in the stroma were characteristic features. Large areas of necrosis
      were also evident. However, mitotic figures were rare (1-2 mitoses per 10 high
      power fields). Many tumor cells were positive for GFAP, and a number were
      positive for neurofilament protein and synaptophysin, indicating their neuronal
      differentiation. In addition, occasional tumor cells were positive for CD34. p53
      protein was entirely negative in the tumor cells. In diagnosing this tumor
      histopathologically, differentiation between PXA and giant cell glioblastoma
      (GCG), a rare variant of glioblastoma, was problematic. However, considering the
      overall histopathological picture, a final diagnosis of PXA with anaplastic
      features was made. The present case indicates that PXA can occur as an
      intraventricular tumor, and suggests that in some instances, it would be very
      difficult to differentiate PXA and GCG histopathologically.

PMID- 20051019
TI  - Dual pathology in Rasmussen's encephalitis: a study of seven cases and review of
      the literature.
AB  - Dual pathology has previously been reported in less than 10% of cases of
      Rasmussen's encephalitis (RE). Given the rarity of RE, it appears unlikely that
      dual pathology in RE is merely a coincidence. We therefore reviewed all cases of
      RE experienced in our institution to assess for an additional/associated
      pathology. A total of seven patients with RE were identified in our archives.
      Seven children (4 boys and 3 girls, age range: 3-16 years, mean: 9.5 years) with
      medically refractory epilepsy underwent surgical resection for intractable
      seizures. The surgical specimens were examined with routine neurohistological
      techniques, and immunohistochemistry was performed with an extensive panel of
      antibodies for viruses, lymphocytes, microglia/macrophages, human leukocyte
      antigen (HLA)-DR, astrocytes, and neurons. Relevant literature was reviewed.
      Microscopically, all seven cases demonstrated the inflammatory pathology of RE in
      the cortex and white matter with leptomeningeal and perivascular lymphocytic
      infiltration, microglial nodules with/without neuronophagia, neuronal loss and
      gliosis. The HLA-DR antibody was extremely helpful in highlighting the extent of
      microglial cell proliferation/activation that was not appreciable with standard
      histology. An unexpected finding in all seven cases was the presence of cortical
      dysplasia. In our series of seven cases, there was co-occurrence of the
      inflammatory/destructive pathology of RE with malformative/dysplastic features in
      cortical architecture in 100% of cases, raising questions about the possible
      relationships between the two entities. Awareness of the possibility of dual
      pathology in RE is important for clinical and pathological diagnosis, and may
      affect the management and outcome of these patients. Immunohistochemistry is very
      helpful to make a definitive diagnosis of both pathologies.

PMID- 20051020
TI  - Metabolic surgery: an evolution through bariatric animal models.
AB  - Metabolic surgery was developed through the application and experience gained
      from bariatric or weight loss procedures. Much of our knowledge from the
      procedures comes from the study of animal models, where they have revealed
      anatomic feasibility, systemic physiological elements and cellular metabolic
      effects. The first generation of operation included the jejunoileal bypass and
      partial ileal bypass that led to the development of the current procedures
      including Roux-en-Y gastric bypass, biliopancreatic diversion, adjustable gastric
      banding and sleeve gastrectomy. These operations carry significant metabolic
      benefits and can reduce the risk of diabetes, heart disease and cancer. Further
      insights from these animal models can reveal genetic, molecular and systemic
      effects that can enhance and develop the next generation of metabolic operations.

PMID- 20051021
TI  - Managing superior vena cava syndrome as a complication of pacemaker implantation:
      a pooled analysis of clinical practice.
AB  - BACKGROUND: Superior vena cava syndrome (SVCS) is a rare complication of
      pacemaker implantation. Numerous methods have been employed to treat this
      condition, ranging from anticoagulation and thrombolysis to surgical
      interventions and stenting. However, thus far only small case series have been
      reported and there is no currently accepted standard of care. METHODS: Our group
      preformed a PubMed literature search to identify cases of symptomatic SVCS that
      developed following implantation of permanent pacemakers or implanatable
      cardioverter defibrillators and were treated with one of five different
      modalities: anticoagulation, thrombolysis, venoplasty, stenting, and surgical
      reconstuction. Duration of follow-up and incidence of recurrence of symptoms were
      the main end-points. RESULTS: One hundred and four eligible cases from 74
      different publications were identified, in which SVCS presented at a median of 48
      (range 0-396) months after device implantation. We found that over the last 40
      years, conservative treatments have been replaced by surgical reconstruction, and
      most recently by stenting, as the most common therapeutic modality employed.
      Anticoagulation, thrombolysis, and venoplasty alone were all associated with high
      recurrence rates. Surgery and stenting were more successful: recurrence rates
      were 12% and 5% over a median follow-up of 16 (range: 2-179) and 9.5 (range: 2
      60) months, respectively. CONCLUSIONS: Currently, transvenous stenting is the
      most common treatment used for pacemaker-related SVCS, usually with conservation
      of the implanted leads. Both surgery and stenting appear to be effective
      treatments, with low incidences of recurrent SVCS over the first 12 months, but
      there is unfortunately a paucity of data on long-term outcomes. (PACE 2010; 420
      425).

PMID- 20051022
TI  - Former small for gestational age (SGA) status is associated to changes of insulin
      resistance in obese children during weight loss.
AB  - OBJECTIVE: Former small for gestational age (SGA) children are at risk of both
      obesity and insulin resistance. Longitudinal studies are required to assess a
      possible relationship between former SGA status and insulin resistance
      independent of weight status. We hypothesized that obese children with former
      appropriate for gestational age (AGA) status improve their insulin resistance
      during weight loss more effectively compared to obese children with former SGA
      status. METHODS: A 1-yr longitudinal follow-up study design was adopted in the
      primary care setting and 341 obese children [8% SGA, mean age 10.5 +/- 0.1 yr,
      body mass index (BMI) 27.7 +/- 0.2, BMI-standard deviation score (SDS) 2.47 +/-
      0.02] were taken for the study. Outpatient 1-yr intervention was based on
      exercise, behavior and nutrition therapy. We measured insulin resistance index
      following the Homeostasis model assessment model (HOMA), blood pressure, lipids,
      glucose, and insulin in all children before and after the 1-yr intervention.
      RESULTS: In a multiple linear regression analysis adjusted for age, gender, and
      pubertal stage, changes of HOMA were significantly related to changes of BMI-SDS
      (-2.55 per loss of 1 BMI-SDS unit; p < 0.001) and SGA status (+2.05 for SGA
      children; p < 0.001). Changes of BMI-SDS together with gender and age explained
      10% of the variance of changes of HOMA, while SGA status explained an additional
      4%. After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status
      was not significantly related to any other considered cardiovascular risk factor.
      CONCLUSIONS: Change of weight status predicted change of HOMA in obese children
      participating in a lifestyle intervention. Changes of HOMA were also predicted by
      former SGA status supporting that former SGA status influences insulin
      resistance.

PMID- 20051023
TI  - Low incidence of hepatic veno-occlusive disease in pediatric patients undergoing
      hematopoietic stem cell transplantation attributed to a combination of
      intravenous heparin, oral glutamine, and ursodiol at a single transplant
      institution.
AB  - We report the low incidence of hepatic VOD in pediatric patients with various
      diagnoses including hematologic malignancies and non-malignant conditions
      transplanted at our institution. Retrospective review of 188 patients who
      underwent HSCT and received a combined prophylactic regimen of intravenous
      heparin, oral glutamine, and ursodiol was undertaken. Analysis of the outcome of
      VOD revealed only one clinical case with acute myeloid leukemia; the patient
      developed hepatic VOD 10 days after receiving myeloablative chemotherapy with
      busulfan and CTX followed by HLA-matched related peripheral blood stem cell
      transplantation. The low incidence of hepatic VOD in an otherwise high-risk
      pediatric transplant population is an important observation, which may be partly
      attributed to this prophylactic regimen, and warrants further randomized clinical
      trials for confirmation.

PMID- 20051024
TI  - Biliary complications after paediatric liver transplantation.

PMID- 20051025
TI  - Size-reduced lung transplantation in children--an option worth to consider!
AB  - Lung transplantation is an accepted therapy for pediatric end-stage lung disease.
      However, there is a shortage of suitable donor organs. Therefore, the use of
      downsized lung allografts seems a valuable option. We report our experience of
      downsized pediatric lung transplantation in comparison with standard full-size
      pediatric lung transplantation over one decade. Pediatric recipients undergoing
      downsized or standard lung transplantation were included (January 1997-December
      2006). We compared pretransplant clinical data and surgical and post-operative
      complications and post-transplant outcome. Ten pediatric lung transplants were
      performed (median patient age 15.6 yr [12.3-17.8]). Nine of 10 patients had CF.
      Five patients underwent standard full-size lung transplantation; five had
      downsized lung transplants. "Downsized" recipients had significantly lower median
      height and weight Z-scores. Donor/recipient length difference was significantly
      greater in the "Downsized" Group (p<0.05). All patients had comparable post
      transplant functional outcome without additional surgical complications or
      morbidities in "downsized" recipients. Median post-transplant survival was 65
      months (5-77) in the "Standard" Group compared to 86 months (64-121) in the
      "Downsized" Group (p=0.1). Our data suggest that downsized lung transplantation
      in pediatric recipients may have post-transplant outcomes comparable to full-size
      lung transplantation without significant complications.

PMID- 20051026
TI  - Pediatric liver transplantation for primary malignant liver tumors with a focus
      on hepatic epithelioid hemangioendothelioma: the UNOS experience.
AB  - Treatment for HEH does not follow a standardized algorithm. From clinical
      experience, it is assumed that pediatric patients with HEH will fare as well as
      other common pediatric liver tumors post-OLT. The UNOS dataset was examined for
      patients with pediatric OLT between 1987 and 2007. Patients were grouped into non
      tumors, HB, HCC, HEH, and rare liver tumors. COD analysis was calculated using
      Fisher's exact test. Patient, allograft, and recurrence-free survival were
      compared using Kaplan-Meier curves and log-rank tests. A total of 366 patients
      with pediatric OLT were identified with primary liver tumors (HB - 237, HCC - 58,
      HEH - 35, other - 36). HEH patient survival (five yr: 60.6%) was poorer than non
      tumor OLTpatient survival (five yr: 84.4%). Survival was worse when compared to
      HB (five yr: 72%) and rare liver tumors (five yr: 78.9%), but better than HCC
      (five yr: 53.5%). Allograft survival in HEH (five yr: 50.1%) lies between HB
      (five yr: 63.6%) and HCC (five yr: 42.8%). COD analysis demonstrates recurrence
      as a major cause in HB and HCC, but not for HEH or other liver tumors. The data
      suggest that patient survival may not be as high as previously believed and
      further investigation is warranted.

PMID- 20051027
TI  - Induction of leaf senescence by low nitrogen nutrition in sunflower (Helianthus
      annuus) plants.
AB  - Different parameters which vary during the leaf development in sunflower plants
      grown with nitrate (2 or 20 mM) for a 42-day period have been determined. The
      plants grown with 20 mM nitrate (N+) showed greater leaf area and specific leaf
      mass than the plants grown with 2 mM nitrate (N-). The total chlorophyll content
      decreased with leaf senescence, like the photosynthetic rate. This decline of
      photosynthetic activity was greater in plants grown with low nitrogen level (N-),
      showing more pronounced senescence symptoms than with high nitrogen (N+). In both
      treatments, soluble sugars increased with aging, while starch content decreased.
      A significant increase of hexose to sucrose ratio was observed at the beginning
      of senescence, and this raise was higher in N- plants than in N+ plants. These
      results show that sugar senescence regulation is dependent on nitrogen,
      supporting the hypothesis that leaf senescence is regulated by the C/N balance.
      In N+ and N- plants, ammonium and free amino acid concentrations were high in
      young leaves and decreased progressively in the senescent leaves. In both
      treatments, asparagine, and in a lower extent glutamine, increased after
      senescence start. The drop in the (Glu+Asp)/(Gln+Asn) ratio associated with the
      leaf development level suggests a greater nitrogen mobilization. Besides, the
      decline in this ratio occurred earlier and more rapidly in N- plants than in N+
      plants, suggesting that the N- remobilization rate correlates with leaf
      senescence severity. In both N+ and N- plants, an important oxidative stress was
      generated in vivo during sunflower leaf senescence, as revealed by lipid
      peroxidation and hydrogen peroxide accumulation. In senescent leaves, the
      increase in hydrogen peroxide levels occurred in parallel with a decline in the
      activity of antioxidant enzymes. In N+ plants, the activities of catalase and
      ascorbate peroxidase (APX) increased to reach their highest values at 28 days,
      and later decreased during senescence, whereas in N- plants these activities
      started to decrease earlier, APX after 16 days and catalase after 22 days,
      suggesting that senescence is accelerated in N-leaves. It is probable that
      systemic signals, such as a deficit in amino acids or other metabolites
      associated with the nitrogen metabolism produced in plants grown with low
      nitrogen, lead to an early senescence and a higher oxidation state of the cells
      of these plant leaves.

PMID- 20051028
TI  - Effects of copper on the photosynthesis of intact chloroplasts: interaction with
      manganese.
AB  - Highly purified, intact chloroplasts were prepared from pea (Pisum sativum L.)
      and spinach (Spinacia oleracea L.) following an identical procedure, and were
      used to investigate the cupric cation inhibition on the photosynthetic activity.
      In both species, copper inhibition showed a similar inhibitor concentration that
      decreases the enzyme activity by 50% (IC(50) approximately 1.8 microM) and did
      not depend on the internal or external phosphate (Pi) concentration, indicating
      that copper did not interact with the Pi translocator. Fluorescence analysis
      suggested that the presence of copper did not facilitate photoinhibition, because
      there were no changes in maximal fluorescence (F(m)) nor in basal fluorescence
      (F(o)) of copper-treated samples. The electron transport through the photosystem
      II (PSII) was also not affected (operating efficiency of PSII-F'v/F'm similar in
      all conditions). Yet, under Cu(2+) stress, the proportion of open PSII reaction
      centers was dramatically decreased, and the first quinone acceptor (Q(A))
      reoxidation was fully inhibited, as demonstrated by the constant photochemical
      quenching (q(P)) along experiment time. The quantum yield of PSII electron
      transport (Phi(PSII)) was also clearly affected by copper, and therefore reduced
      the photochemistry efficiency. Manganese, when added simultaneously with copper,
      delayed the inhibition, as measured by oxygen evolution and chlorophyll
      fluorescence, but neither reversed the copper effect when added to copper
      inhibited plastids, nor prevented the inhibition of the Hill activity of isolated
      copper-treated thylakoids. Our results suggest that manganese competed with
      copper to penetrate the chloroplast envelope. This competition seems to be
      specific because other divalent cations e.g. magnesium and calcium, did not
      interfere with the copper action in intact chloroplasts. All results do suggest
      that, under these conditions, the stroma proteins, such as the Calvin-Benson
      cycle enzymes or others are the most probable first target for the Cu(2+) action,
      resulting in the total inhibition of chloroplast photosynthesis and in the
      consequent unbalanced rate of production and consumption of the reducing power.

PMID- 20051029
TI  - A fluorometer-based method for monitoring oxidation of redox-sensitive GFP
      (roGFP) during development and extended dark stress.
AB  - Redox-sensitive GFP (roGFP) localized to different compartments has been shown to
      be suitable for determination of redox potentials in plants via imaging. Long
      term measurements bring out the need for analyzing a large number of samples
      which are averaged over a large population of cells. Because this goal is too
      tedious to be achieved by confocal imaging, we have examined the possibility of
      using a fluorometer to monitor changes in roGFP localized to different
      subcellular compartments during development and dark-induced senescence. The
      degree of oxidations determined by a fluorometer for different probes was similar
      to values obtained by confocal image analysis. Comparison of young and old leaves
      indicated that in younger cells higher levels of H(2)O(2) were required to
      achieve full roGFP oxidation, a parameter which is necessary for calculation of
      the degree of oxidation of the probe and the actual redox potential. Therefore,
      it is necessary to carefully determine the H(2)O(2) concentration required to
      achieve full oxidation of the probe. In addition, there is an increase in
      autofluorescence during development and extended dark stress, which might
      interfere with the ability to detect changes in oxidation-reduction dependent
      fluorescence of roGFP. Nevertheless, it was possible to determine the full
      dynamic range between the oxidized and the reduced forms of the different probes
      in the various organelles until the third day of darkness and during plant
      development, thereby enabling further analysis of probe oxidation. Hence,
      fluorometer measurements of roGFP can be used for extended measurements enabling
      the processing of multiple samples. It is envisaged that this technology may be
      applicable to the analysis of redox changes in response to other stresses or to
      various mutants.

PMID- 20051030
TI  - The responses of light interception, photosynthesis and fruit yield of cucumber
      to LED-lighting within the canopy.
AB  - Mathematical models of light attenuation and canopy photosynthesis suggest that
      crop photosynthesis increases by more uniform vertical irradiance within crops.
      This would result when a larger proportion of total irradiance is applied within
      canopies (interlighting) instead of from above (top lighting). These irradiance
      profiles can be generated by Light Emitting Diodes (LEDs). We investigated the
      effects of interlighting with LEDs on light interception, on vertical gradients
      of leaf photosynthetic characteristics and on crop production and development of
      a greenhouse-grown Cucumis sativus'Samona' crop and analysed the interaction
      between them. Plants were grown in a greenhouse under low natural irradiance
      (winter) with supplemental irradiance of 221 micromol photosynthetic photon flux
      m(-2) s(-1) (20 h per day). In the interlighting treatment, LEDs (80% Red, 20%
      Blue) supplied 38% of the supplemental irradiance within the canopy with 62% as
      top lighting by High-Pressure Sodium (HPS)-lamps. The control was 100% top
      lighting (HPS lamps). We measured horizontal and vertical light extinction as
      well as leaf photosynthetic characteristics at different leaf layers, and
      determined total plant production. Leaf mass per area and dry mass allocation to
      leaves were significantly greater but leaf appearance rate and plant length were
      smaller in the interlighting treatment. Although leaf photosynthetic
      characteristics were significantly increased in the lower leaf layers,
      interlighting did not increase total biomass or fruit production, partly because
      of a significantly reduced vertical and horizontal light interception caused by
      extreme leaf curling, likely because of the LED-light spectrum used, and partly
      because of the relatively low irradiances from above.

PMID- 20051031
TI  - Glutamate induces series of action potentials and a decrease in circumnutation
      rate in Helianthus annuus.
AB  - Reports concerning the function of glutamate (Glu) in the electrical and movement
      phenomena in plants are scarce. Using the method of extracellular measurement, we
      recorded electrical potential changes in the stem of 3-week-old Helianthus annuus
      L. plants after injection of Glu solution. Simultaneously, circumnutation
      movements of the stem were measured with the use of time-lapse images. Injection
      of Glu solution at millimolar (200, 50, 5 mM) concentrations in the basal part of
      the stem evoked a series of action potentials (APs). The APs appeared in the site
      of injection and in different parts of the stem and were propagated acropetally
      and/or basipetally along the stem. Glu injection also resulted in a transient,
      approximately 5-h-long decrease in the stem circumnutation rate. The APs
      initiated and propagating in the sunflower stem after Glu injection testify the
      existence of a Glu perception system in vascular plants and suggest its
      involvement in electrical, long-distance signaling. Our experiments also
      demonstrated that Glu is a factor affecting circumnutation movements.

PMID- 20051032
TI  - Tubers from potato lines expressing a tomato Kunitz protease inhibitor are
      substantially equivalent to parental and transgenic controls.
AB  - Recombinant protease inhibitors represent useful tools for the development of
      insect-resistant transgenic crops, but questions have been raised in recent years
      about the impact of these proteins on endogenous proteases and chemical
      composition of derived food products. In this study, we performed a detailed
      compositional analysis of tubers from potato lines expressing the broad-spectrum
      inhibitor of Ser and Asp proteases, tomato cathepsin D inhibitor (SlCDI), to
      detect possible unintended effects on tuber composition. A compositional analysis
      of key nutrients and toxic chemicals was carried out with tubers of SlCDI
      expressing and control (comparator) lines, followed by a two-dimensional gel
      electrophoresis (2-DE) proteomic profiling of total and allergenic proteins to
      detect eventual effects at the proteome level. No significant differences were
      observed among control and SlCDI-expressing lines for most chemicals assayed, in
      line with the very low abundance of SlCDI in tubers. Likewise, proteins detected
      after 2-DE showed no quantitative variation among the lines, except for a few
      proteins in some control and test lines, independent of slcdi transgene
      expression. Components of the patatin storage protein complex and Kunitz protease
      inhibitors immunodetected after 2-DE showed unaltered deposition patterns in
      SlCDI-expressing lines, clearly suggesting a null impact of slcdi on the
      intrinsic allergenic potential of potato tubers. These data suggest, overall, a
      null impact of slcdi expression on tuber composition and substantial equivalence
      between comparator and SlCDI-expressing tubers despite reported effects on leaf
      protein catabolism. They also illustrate the usefulness of proteomics as a tool
      to assess the authenticity of foods derived from novel-generation transgenic
      plants.

PMID- 20051033
TI  - A companion protease inhibitor for the protection of cytosol-targeted recombinant
      proteins in plants.
AB  - We reported earlier the potential of tomato cathepsin D inhibitor (SlCDI) as an
      in-built stabilizing agent for the protection of recombinant proteins in
      transgenic plant leaf crude extracts (Plant Biotechnol J.4, 359-368). Here we
      document the potential of SlCDI for the in situ protection of proteins in potato
      leaves. Total protein assays with control and SlCDI-expressing potato lines
      indicated a positive impact of slcdi transgene expression on leaf protein
      content, with a mean relative increase of 35%-40% depending on the light regime.
      Out of approximately 700 proteins detected on 2-D gels, only 20 exhibited a
      significantly altered level on a protein-specific basis, whereas most proteins
      were up-regulated on a leaf fresh weight basis, albeit at variable rates.
      Quantitative reverse trancriptase-PCR assays for rubisco activase showed similar
      transcript levels in leaves of test and control lines despite protein levels
      increased by two- to threefold in SlCDI-expressing lines. These observations,
      along with the unrelated biological functions assigned to MS-identified proteins
      up-regulated in leaves and protease assays showing slightly increased proteasome
      activity in protein extracts of SlCDI-expressing lines, suggest a general,
      proteasome-independent protein stabilizing effect of SlCDI in planta. Transient
      expression assays with human alpha(1)-antichymotrypsin also showed a stabilizing
      effect for SlCDI on heterologous proteins, leading to net levels of the human
      protein increased by approximately 2.5-fold in SlCDI-expressing plants. These
      data illustrate, overall, the potential of SlCDI as an in vivo protein
      stabilizing agent in transgenic plant systems, useful to improve protein levels
      and recombinant protein accumulation.

PMID- 20051034
TI  - Transgenic maize lines with cell-type specific expression of fluorescent proteins
      in plastids.
AB  - Plastid number and morphology vary dramatically between cell types and at
      different developmental stages. Furthermore, in C4 plants such as maize,
      chloroplast ultrastructure and biochemical functions are specialized in mesophyll
      and bundle sheath cells, which differentiate acropetally from the proplastid form
      in the leaf base. To develop visible markers for maize plastids, we have created
      a series of stable transgenics expressing fluorescent proteins fused to either
      the maize ubiquitin promoter, the mesophyll-specific phosphoenolpyruvate
      carboxylase (PepC) promoter, or the bundle sheath-specific Rubisco small subunit
      1 (RbcS) promoter. Multiple independent events were examined and revealed that
      maize codon-optimized versions of YFP and GFP were particularly well expressed,
      and that expression was stably inherited. Plants carrying PepC promoter
      constructs exhibit YFP expression in mesophyll plastids and the RbcS promoter
      mediated expression in bundle sheath plastids. The PepC and RbcS promoter fusions
      also proved useful for identifying plastids in organs such as epidermis, silks,
      roots and trichomes. These tools will inform future plastid-related studies of
      wild-type and mutant maize plants and provide material from which different
      plastid types may be isolated.

PMID- 20051035
TI  - Tobacco as a production platform for biofuel: overexpression of Arabidopsis DGAT
      and LEC2 genes increases accumulation and shifts the composition of lipids in
      green biomass.
AB  - When grown for energy production instead for smoking, tobacco can generate a
      large amount of inexpensive biomass more efficiently than almost any other
      agricultural crop. Tobacco possesses potent oil biosynthesis machinery and can
      accumulate up to 40% of seed weight in oil. In this work, we explored two
      metabolic engineering approaches to enhance the oil content in tobacco green
      tissues for potential biofuel production. First, an Arabidopsis thaliana gene
      diacylglycerol acyltransferase (DGAT) coding for a key enzyme in triacylglycerol
      (TAG) biosynthesis, was expressed in tobacco under the control of a strong
      ribulose-biphosphate carboxylase small subunit promoter. This modification led to
      up to a 20-fold increase in TAG accumulation in tobacco leaves and translated
      into an overall of about a twofold increase in extracted fatty acids (FA) up to
      5.8% of dry biomass in Nicotiana tabacum cv Wisconsin, and up to 6% in high-sugar
      tobacco variety NC-55. Modified tobacco plants also contained elevated amounts of
      phospholipids. This increase in lipids was accompanied by a shift in the FA
      composition favourable for their utilization as biodiesel. Second, we expressed
      in tobacco Arabidopsis gene LEAFY COTYLEDON 2 (LEC2), a master regulator of seed
      maturation and seed oil storage under the control of an inducible Alc promoter.
      Stimulation of LEC2 expression in mature tobacco plants by acetaldehyde led to
      the accumulation of up to 6.8% per dry weight of total extracted FA. The obtained
      data reveal the potential of metabolically modified plant biomass for the
      production of biofuel.

PMID- 20051037
TI  - Production of compact plants by overexpression of AtSHI in the ornamental
      Kalanchoe.
AB  - Growth retardation is an important breeding aim and an essential part of
      horticultural plant production. Here, the potential of transferring the
      Arabidopsis short internode (shi) mutant phenotype was explored by expressing the
      AtSHI gene in the popular ornamental plant Kalanchoe. A 35S-AtSHI construct was
      produced and transferred into eight genetically different cultivars of Kalanchoe
      by Agrobacterium tumefaciens. The resulting transgenic plants showed dwarfing
      phenotypes like reduced plant height and diameter, and also more compact
      inflorescences, as a result of increased vegetative height. The shi phenotype was
      stable over more than five vegetative subcultivations. Compared with Arabidopsis,
      the ectopic expression of AtSHI in Kalanchoe showed several differences. None of
      the Kalanchoe SHI-lines exhibited alterations in leaf colour or morphology, and
      most lines were not delayed in flowering. Moreover, continuous treatment of lines
      delayed in flowering with low concentrations of gibberellins completely restored
      the time of flowering. These features are very important as a delay in flowering
      would increase plant production costs significantly. The effect of expression
      controlled by the native Arabidopsis SHI promoter was also investigated in
      transgenic Kalanchoe and resulted in plants with a longer flowering period. Two
      AtSHI like genes were identified in Kalanchoe indicating a widespread presence of
      this transcription factor. These findings are important because they suggest that
      transformation with the AtSHI gene could be applied to several species as a tool
      for growth retardation, and that this approach could substitute the use of
      conventional chemical growth regulation in plant production.

PMID- 20051036
TI  - Chloroplast-derived vaccine antigens confer dual immunity against cholera and
      malaria by oral or injectable delivery.
AB  - Cholera and malaria are major diseases causing high mortality. The only licensed
      cholera vaccine is expensive; immunity is lost in children within 3 years and
      adults are not fully protected. No vaccine is yet available for malaria.
      Therefore, in this study, the cholera toxin-B subunit (CTB) of Vibrio cholerae
      fused to malarial vaccine antigens apical membrane antigen-1 (AMA1) and merozoite
      surface protein-1 (MSP1) was expressed in lettuce and tobacco chloroplasts.
      Southern blot analysis confirmed homoplasmy and stable integration of transgenes.
      CTB-AMA1 and CTB-MSP1 fusion proteins accumulated up to 13.17% and 10.11% (total
      soluble protein, TSP) in tobacco and up to 7.3% and 6.1% (TSP) in lettuce,
      respectively. Nine groups of mice (n = 10/group) were immunized subcutaneously
      (SQV) or orally (ORV) with purified antigens or transplastomic tobacco leaves.
      Significant levels of antigen-specific antibody titres of immunized mice
      completely inhibited proliferation of the malarial parasite and cross-reacted
      with the native parasite proteins in immunoblots and immunofluorescence studies.
      Protection against cholera toxin challenge in both ORV (100%) and SQV (89%) mice
      correlated with CTB-specific titres of intestinal, serum IgA and IgG1 in ORV and
      only IgG1 in SQV mice, but no other immunoglobulin. Increasing numbers of
      interleukin-10(+) T cell but not Foxp3(+) regulatory T cells, suppression of
      interferon-gamma and absence of interleukin-17 were observed in protected mice,
      suggesting that immunity is conferred via the Tr1/Th2 immune response. Dual
      immunity against two major infectious diseases provided by chloroplast-derived
      vaccine antigens for long-term (>300 days, 50% of mouse life span) offers a
      realistic platform for low cost vaccines and insight into mucosal and systemic
      immunity.

PMID- 20051038
TI  - The effect of the heterologous expression of Phragmites australis gamma
      glutamylcysteine synthetase on the Cd2+ accumulation of Agrostis palustris.
AB  - Heavy metal pollution has become one of the most serious environmental problems
      today. To develop a more efficient plant to clean up heavy metal contaminated
      soils, a gamma-glutamylcysteine synthetase (GCS) cDNA, named PaGCS, was isolated
      by PCR from Phragmites australis. The PaGCS sequence was transformed via
      agroinfection into the heavy metal intolerant grass Agrostis palustris. Five
      confirmed transgenic A. palustris plants expressing PaGCS were compared with the
      wild-type line for growth and Cd(2+) accumulation, as well as for the expression
      of a number of phytochelatin synthesis and stress-responsive enzymes when
      challenged with Cd(2+) stress. GCS and phytochelatin synthase (PCS) were up
      regulated in the transgenic lines. All the transgenic lines accumulated more
      Cd(2+) and phytochelatins (PCs) than the wild-type line, and three of the five
      lines grew more effectively than the wild-type after either five or 21 d of
      Cd(2+) stress. Variation among the transgenics was observed for the distribution
      of Cd(2+) in the root, shoot and leaf. The malondialdehyde content of all the
      transgenic lines was lower than that of the wild type under Cd(2+) treatment,
      while the activity of both superoxide dismutase and peroxidase present in the
      transgenic lines increased markedly 24 h after Cd(2+) stress, and then rapidly
      declined.

PMID- 20051039
TI  - Do photosynthetic limitations of evergreen Quercus ilex leaves change with long
      term increased drought severity?
AB  - Seasonal drought can severely impact leaf photosynthetic capacity. This is
      particularly important for Mediterranean forests, where precipitation is expected
      to decrease as a consequence of climate change. Impacts of increased drought on
      the photosynthetic capacity of the evergreen Quercus ilex were studied for two
      years in a mature forest submitted to long-term throughfall exclusion. Gas
      exchange and chlorophyll fluorescence were measured on two successive leaf
      cohorts in a control and a dry plot. Exclusion significantly reduced leaf water
      potential in the dry treatment. In both treatments, light-saturated net
      assimilation rate (A(max)), stomatal conductance (g(s)), maximum carboxylation
      rate (V(cmax)), maximum rate of electron transport (J(max)), mesophyll
      conductance to CO2 (g(m)) and nitrogen investment in photosynthesis decreased
      markedly with soil water limitation during summer. The relationships between leaf
      photosynthetic parameters and leaf water potential remained identical in the two
      treatments. Leaf and canopy acclimation to progressive, long-term drought
      occurred through changes in leaf area index, leaf mass per area and leaf chemical
      composition, but not through modifications of physiological parameters.

PMID- 20051040
TI  - Species-specific activation time-lags can explain habitat restrictions in
      hydrophilic lichens.
AB  - Photosystem II (PSII) activation after hydration with water or humid air was
      measured in four hydrophilic and a generalist lichen to test the hypothesis that
      slow activation might explain habitat restriction in the former group. For the
      hydrophilic species, activation was after 4 h nearly completed in Lobaria
      amplissima and Platismatia norvegica, while only c. 50% for Bryoria bicolor and
      Usnea longissima. The generalist Platismatia glauca was activated
      instantaneously. The effect of this on lichen field performance was investigated
      using a dynamic model separating the two water sources rain and humid air. Model
      simulations were made using the species-specific characteristics and climate data
      from 12 stream microhabitats. For U. longissima, slow PSII activation could
      reduce realized photosynthesis by a factor of five. Bryoria bicolor was almost as
      severely affected, while P. norvegica displayed moderate reductions. Lobaria
      amplissima displayed longer realized activity periods even in unfavourable
      microclimates, possibly because of a higher water loss resistance. Both close
      proximity to streams and presence of turbulent water had a positive impact on
      realized activity among the slowly activated species, coinciding with observed
      distribution patterns of hydrophilic species. The results presented here may thus
      partly explain observed habitat restrictions of rare hydrophilic lichens.

PMID- 20051041
TI  - Modelling hydration and photosystem II activation in relation to in situ rain and
      humidity patterns: a tool to compare performance of rare and generalist epiphytic
      lichens.
AB  - A dynamic water and activity model was developed to assess how efficiently
      lichens can exploit in situ rain and humid air. The capacity to rehydrate and
      activate photosynthesis [i.e. photosystem II (PSII)] by these water sources was
      compared among four hydrophilic and one generalist epiphytic lichen. Hydration
      status, potential (instant activation) and realized (delayed activation) day
      light activity were simulated using a model based on species-specific hydration,
      PSII activation characteristics and in situ water content for Platismatia
      norvegica in three microclimatic scenarios. The results showed that delayed PSII
      activation could have profound effects on lichens' ability to exploit
      environmental water sources. During rain, realized activity was reduced by 19, 34
      and 56% compared to simulations assuming instant activation for three hydrophilic
      lichens in the driest microclimate. During humid air, the reduction was 81% for
      the most extreme species and scenario, because of slow hydration and low
      equilibrium water content. Many and brief hydration events may thus hamper
      species with slow activation and fast desiccation kinetics. No evidence of
      compensation by a 'water-holding' morphology was observed among studied species.
      The developed model may provide a tool for identifying suitable habitats for long
      term persistence of lichens with physiological constraints.

PMID- 20051042
TI  - Fertility time trends in dairy herds in northern Portugal.
AB  - The economics of dairy production are in great part dictated by the reproductive
      efficiency of the herds. Many studies have reported a widespread decrease in
      fertility of dairy cows. In a previous work (Rocha et al. 2001), we found a very
      poor oestrus detection rate (38%), and consequently a delayed calving to 1st AI
      and calving to conception intervals. However, a good conception rate at 1st AI
      was noted (51%) resulting in a low number of inseminations per pregnancy (IAP)
      (1.4). Here, results from a subsequent fertility time trend assessment study
      carried out in the same region for cows born from 1992 to 2002 are reported.
      Statistical linear models were used to analyse the data. Estimate linear
      contrasts of least square means were computed from each model. The number of
      observations per studied index varied from 12,130 (culling rate) to 57,589 (non
      return rate). Mean age at first calving was 28.9 +/- 0.14 months, without (p >
      0.05) variation over time. There was a small, but significant (p < 0.05),
      deterioration of all other parameters. Non-return rates at 90 days and calving
      rate at 1st AI decreased 0.3% per trimester, with a consequent increase of 0.04
      IA/parturition. Oestrus detection rate decreased 0.13% per year, and calving at
      1st AI and calving-conception intervals increased 0.17 and 0.07 days/year
      respectively, while intercalving interval increased 1.7 days per year. From
      12,130 cows calving, only 1,816 had a 4th lactation (85% culling/losses). The
      data was not meant to draw conclusions on the causes for the decreased fertility
      over time, but an increase of milk production from 6537 kg to 8590 kg (305 days)
      from 1996 to 2002 is probably one factor to take into consideration. Specific
      measures to revert or slow down this trend of decreasing fertility are warranted.
      Available strategies are discussed.

PMID- 20051044
TI  - Emerging technologies for the thorax: indications, management and complications.
AB  - The field of interventional pulmonology has rapidly expanded to include the
      management and treatment of complex diseases of the chest. The management of
      central airway obstruction, pleural disease diagnosis, treatment and palliation,
      advanced bronchoscopic techniques to aid in the diagnosis of lung cancer and
      innovative therapies to treat asthma and COPD have all emerged over the past
      decade. As astute clinicians, we are all aware of the risks and benefits of using
      these therapies to treat our patients. In order to appropriately treat and manage
      these often complex medical situations, the physician should have an expert
      knowledge of all available modalities, the expertise to safely perform the
      procedure and the ability to minimize the risk of and manage the associated
      complications that may arise. In this chapter we review and update some of the
      bronchoscopic and pleural interventions offered by interventional pulmonologists
      as well as the associated complications and management.

PMID- 20051045
TI  - Comparison of pulmonary diseases in common variable immunodeficiency and X-linked
      agammaglobulinaemia.
AB  - Patients with CVID are at greater risk of developing lung complications than
      patients with XLA because of delayed diagnosis and possible immune dysregulation.
      Early diagnosis and appropriate treatment reduces the incidence of pulmonary
      infections in both groups of patients. However, CVID patients are prone to
      progressive lung disease despite optimal immunoglobulin therapy. BACKGROUND AND
      OBJECTIVE: Pulmonary disease is the most common complication in patients with
      common variable immunodeficiency (CVID) or X-linked agammaglobulinaemia (XLA).
      Pulmonary disease may progress despite immunoglobulin replacement therapy. In
      this study pulmonary complications were compared in patients with CVID or XLA.
      METHODS: Pulmonary complications were evaluated in 115 patients (76 with CVID and
      39 with XLA) by reviewing hospital records of chest infections, pulmonary
      function tests and high-resolution CT scans. RESULTS: Thirty-two patients with
      XLA (82%) presented with 59 episodes of pneumonia before diagnosis, whereas 15
      patients (38.4%) experienced pneumonia after immunoglobulin replacement therapy
      (1.67 vs 0.45 episodes per patient per year). Among the CVID patients, 196
      episodes of pneumonia were documented in 59 patients (77.6%) before diagnosis,
      while 36 patients (47.3%) experienced pneumonia after therapy (1.11 vs 0.58
      episodes of pneumonia per patient per year). Forty-seven (41%) patients (38 with
      CVID and 9 with XLA) developed chronic lung disease. The CVID patients developed
      more complications, including bronchiectasis and lymphoid interstitial
      pneumonitis, than the XLA patients. CONCLUSIONS: Patients with CVID had a greater
      likelihood of developing lung disease, possibly due to delayed diagnosis and
      immune dysregulation, as compared with XLA patients. Early diagnosis of patients
      with primary antibody deficiencies and adequate i.v. immunoglobulin replacement
      therapy substantially reduces the number of pulmonary infections. However, CVID
      patients are prone to progression of lung disease despite optimal immunoglobulin
      therapy because of the nature of the disease. This important issue should be
      addressed in further studies.

PMID- 20051046
TI  - Non-invasive positive pressure ventilation during sleep at 3800 m: Relationship
      to acute mountain sickness and sleeping oxyhaemoglobin saturation.
AB  - Overnight oxyhaemoglobin desaturation is related to AMS. AMS can be debilitating
      and may require descent. Positive pressure ventilation during sleep at high
      altitude may prevent AMS and therefore be useful in people travelling to high
      altitude, who are known to suffer from AMS. BACKGROUND AND OBJECTIVE: Ascent to
      high altitude results in hypobaric hypoxia and some individuals will develop
      acute mountain sickness (AMS), which has been shown to be associated with low
      oxyhaemoglobin saturation during sleep. Previous research has shown that positive
      end-expiratory pressure by use of expiratory valves in a face mask while awake
      results in a reduction in AMS symptoms and higher oxyhaemoglobin saturation. We
      aimed to determine whether positive pressure ventilation would prevent AMS by
      increasing oxygenation during sleep. METHODS: We compared sleeping oxyhaemoglobin
      saturation and the incidence and severity of AMS in seven subjects sleeping for
      two consecutive nights at 3800 m above sea level using either non-invasive
      positive pressure ventilation that delivered positive inspiratory and expiratory
      airway pressure via a face mask, or sleeping without assisted ventilation. The
      presence and severity of AMS were assessed by administration of the Lake Louise
      questionnaire. RESULTS: We found significant increases in the mean and minimum
      sleeping oxyhaemoglobin saturation and decreases in AMS symptoms in subjects who
      used positive pressure ventilation during sleep. Mean and minimum sleeping SaO2
      was lower in subjects who developed AMS after the night spent without positive
      pressure ventilation. CONCLUSIONS: The use of positive pressure ventilation
      during sleep at 3800 m significantly increased the sleeping oxygen saturation; we
      suggest that the marked reduction in symptoms of AMS is due to this higher
      sleeping SaO2. We agree with the findings from previous studies that the
      development of AMS is associated with a lower sleeping oxygen saturation.

PMID- 20051047
TI  - Surgery should be the first line of treatment for empyema.
AB  - Few thoracic conditions present such considerable challenges as pleural space
      infections, herein termed 'empyema' as a general term. Patients may present with
      free-flowing infected pleural effusions that readily drain by catheter or, at the
      other extreme, with organized intrapleural collections of pus with thick pleural
      peels that require open decortication. In the transition from a simple to complex
      empyema, patients pass through the intermediary, or 'fibrinopurulent' stage. Such
      patients require careful assessment to determine the ideal management approach.
      Although existing trials provide insufficient evidence to standardize drainage
      approaches, an accepted principle directs clinicians to drain empyemas promptly
      and completely. In this pro-con presentation, two recognized experts on empyema-
      a thoracic surgeon and an interventional radiologist-approach management from
      decidedly opposite perspectives. The surgeon prefers video-assisted thoracoscopic
      surgery as primary therapy for fibrinopurulent empyemas. The radiologist counters
      that imaging-guided, small-bore catheters, sometimes with adjunctive fibrinolytic
      drugs, provide effective therapy for select patients. In the absence of high
      quality data to settle this debate, both experts present reasoned and thoughtful
      approaches, which produce superior clinical outcomes in their own institutions.
      So readers should recognize that controversy exists in empyema management and
      carefully review each expert's comments. Within each are essential elements of
      care that can be integrated into a multidisciplinary approach. Readers may
      conclude from this debate that each institution should develop a collaborative
      model for managing empyemas that integrates differing expertise to customize care
      for individual patients and continuously measure and improve their patients'
      outcomes.

PMID- 20051048
TI  - Clinical characteristics of combined pulmonary fibrosis and emphysema.
AB  - This study describes the clinical characteristics of patients with CPFE and
      compares these with patients with COPD. It should therefore be noteworthy that
      the prevalence of lung cancer might be high in CPFE patients. BACKGROUND AND
      OBJECTIVE: Patients with combined pulmonary fibrosis and emphysema (CPFE) are
      sometimes seen, and we speculate that these patients have some different clinical
      characteristics from COPD patients. This study clarifies the clinical
      characteristics of CPFE patients. METHODS: This was a retrospective study of 47
      stable patients with concurrent emphysema and diffuse parenchymal lung disease
      with fibrosis, based on the findings of chest CT (CPFE patients). The clinical
      characteristics of CPFE patients were compared with those of emphysema-dominant
      COPD patients without parenchymal lung disease (COPD patients). RESULTS: Forty
      six of the 47 CPFE patients were male. Paraseptal emphysema was particularly
      common in the CPFE group. Honeycombing, ground-glass opacities and reticular
      opacities were present in 75.6%, 62.2% and 84.4% of CPFE patients, respectively.
      Twenty-two of the 47 CPFE patients (46.8%) had lung cancer. Pulmonary function
      tests showed that the CPFE group had milder airflow limitation and lower
      diffusing capacity than the COPD group. Desaturation during 6-min walking test in
      CPFE patients tended to be more severe than in COPD patients, if the level of
      FEV1 or 6MWD was equal. CONCLUSIONS: CPFE patients had some different clinical
      characteristics in comparison with COPD patients and may also have a high
      prevalence of lung cancer.

PMID- 20051049
TI  - Trafficking of MHC class II in dendritic cells is dependent on but not regulated
      by degradation of its associated invariant chain.
AB  - In dendritic cells (DC), newly synthesized MHCII is directed to endosomes by its
      associated invariant chain (Ii). Here, Ii is degraded after which MHCII is loaded
      with peptides. In immature DC, ubiquitination of peptide-loaded MHCII drives its
      sorting to lysosomes for degradation. Ubiquitination of MHCII is strongly reduced
      in response to inflammatory stimuli, resulting in increased expression of MHCII
      at the plasma membrane. Whether surface exposure of MHCII is also regulated
      during DC maturation by changing the rate of Ii degradation remained unresolved
      by conflicting results in the literature. We here pinpoint experimental problems
      that have contributed to these controversies and demonstrate that immature and
      mature DC degrade Ii equally efficient at proper culture conditions. Only when DC
      were cultured in glutamine containing media, endosome acidification and Ii
      degradation were restricted in immature DC and enhanced in response to
      lipopolysaccharide (LPS). These effects are caused by ammonia, a glutamine
      decomposition product. This artificial behavior could be prevented by culturing
      DC in media containing a stable dipeptide as glutamine source. We conclude that
      Ii degradation is a prerequisite for but not a rate limiting step in MHCII
      processing.

PMID- 20051051
TI  - West Nile virus in 2006 and 2007: the Canadian Blood Services' experience.
AB  - BACKGROUND: The Canadian blood supply has been screened for West Nile virus (WNV)
      since 2003. A strategy for targeted individual-donation nucleic acid testing (ID
      NAT) was implemented in 2004 to identify potentially infectious donations that
      may be missed by minipool (MP) testing. In 2007, Canada experienced a larger
      epidemic than in previous years providing an opportunity to evaluate the ID-NAT
      triggering algorithm in higher-risk areas. STUDY DESIGN AND METHODS: A specially
      created database and internal-external communication identified regions for
      targeted ID-NAT using MP and community triggers. WNV-positive donations
      identified by ID-NAT were reexamined in MP to assess the efficacy of targeted ID
      NAT in identifying potentially infectious donations that may have been missed by
      MP testing. WNV-positive donation data from 2006 and 2007 were analyzed to
      examine temporal and geographic trends. A telephone survey about symptoms was
      carried out after the 2007 season. RESULTS: In total 78 WNV-positive donations
      were identified (66 true-positives and four false-positives being in 2007). Most
      positive donations were in the late summer, concentrated in the same western
      provinces as community cases. Fifty-two donations were identified by ID-NAT and
      46% were consistently positive in MP. Of the other 54%, 74% were immunoglobulin
      (Ig)M- and/or IgG-positive. Fifty-six percent of donors experienced mostly mild
      symptoms before or after donation (but all said they were well at the time of
      donation). CONCLUSION: WNV-positive donations correspond geographically with the
      epidemic. MP testing identifies most potentially infectious donations with a
      smaller potential benefit from targeted ID-NAT. Mild symptoms are common but may
      not deter donation.

PMID- 20051050
TI  - Gangliosides and beta1-integrin are required for caveolae and membrane domains.
AB  - Caveolae are plasma membrane domains involved in the uptake of certain pathogens
      and toxins. Internalization of some cell surface integrins occurs via caveolae
      suggesting caveolae may play a crucial role in modulating integrin-mediated
      adhesion and cell migration. Here we demonstrate a critical role for gangliosides
      (sialo-glycosphingolipids) in regulating caveolar endocytosis in human skin
      fibroblasts. Pretreatment of cells with endoglycoceramidase (cleaves
      glycosphingolipids) or sialidase (modifies cell surface gangliosides and
      glycoproteins) selectively inhibited caveolar endocytosis by >70%, inhibited the
      formation of plasma membrane domains enriched in sphingolipids and cholesterol
      ('lipid rafts'), reduced caveolae and caveolin-1 at the plasma membrane by
      approximately 80%, and blunted activation of beta1-integrin, a protein required
      for caveolar endocytosis in these cells. These effects could be reversed by a
      brief incubation with gangliosides (but not with asialo-gangliosides or other
      sphingolipids) at 10 degrees C, suggesting that sialo-lipids are critical in
      supporting caveolar endocytosis. Endoglycoceramidase treatment also caused a
      redistribution of focal adhesion kinase, paxillin, talin, and PIP Kinase Igamma
      away from focal adhesions. The effects of sialidase or endoglycoceramidase on
      membrane domains and the distribution of caveolin-1 could be recapitulated by
      beta1-integrin knockdown. These results suggest that both gangliosides and beta1
      integrin are required for maintenance of caveolae and plasma membrane domains.

PMID- 20051052
TI  - Consensus recommendations of pediatric transfusion medicine objectives for
      clinical pathology residency training programs.
AB  - BACKGROUND: Pediatric transfusion medicine (PTM) is a subspecialty of transfusion
      medicine with no formal training program and few specialists. The Pediatric
      Transfusion Medicine Academic Awardees (PedsTMAA) group surveyed PTM content
      experts to identify relevant objectives for the first formal PTM curriculum.
      STUDY DESIGN AND METHODS: Eight North American PTM experts were invited to
      participate in a two-step consensus process. PTM-related objectives compiled from
      a review of existing training documents were organized into a survey. Experts
      were asked to rate each objective for relevancy for a clinical pathology trainee.
      Content validity indexes (CVIs) and asymmetric confidence intervals (ACIs) of
      expert ratings and analysis of respondents' comments were used to identify
      relevant objectives. RESULTS: Six experts participated and reviewed 117
      objectives. Based on content validity criteria (CVI > or = 0.83 and lower-limit
      95% ACI > or = 3), a total of 65 objectives were considered relevant. Twenty
      three objectives were rated "very relevant" by all the experts while some
      proposed objectives were determined to be not relevant, out of date, or
      inappropriate for a resident trainee level. CONCLUSIONS: The PedsTMAA group
      identified 65 objectives for a PTM curriculum. Twenty-three represent a clear
      core set of objectives and should be considered for clinical pathology training.
      The next step is to consider the teaching strategies and evaluation methods that
      will be employed to best deliver this content addressing competency in medical
      knowledge.

PMID- 20051053
TI  - Exploring opinions and beliefs about cord blood donation among Hispanic and non
      Hispanic black women.
AB  - BACKGROUND: Despite higher birth rates among non-Hispanic blacks and Hispanics,
      the availability of umbilical cord blood from these groups is lower due to lower
      donation rates than that of non-Hispanic whites. Similar racial and ethnic
      disparities in donation rates have been found for blood and organ donation. This
      study is among the first to explore beliefs and attitudes toward umbilical cord
      blood donation among Hispanic and non-Hispanic black women. STUDY DESIGN AND
      METHODS: Five focus groups composed of Hispanic and non-Hispanic black women were
      conducted to explore how women conceptualize information needs about umbilical
      cord blood donation and from whom women want to receive information about
      donation. Participants were adult women who had given birth within the past year
      or were pregnant. RESULTS: Lack of basic information regarding umbilical cord
      blood, its harvesting and use, and the steps and conditions necessary to donate
      were primary barriers to donation. Women expressed confusion over the differences
      between "donation" and "banking." The social value of donation was explicitly
      weighed in terms of the cost of the donation effort. Doctors were viewed as
      critical sources for information about donation, although women expressed
      skepticism about doctors' ability to convey sufficient information during short
      office visits. CONCLUSION: Efforts to increase donation rates among Hispanic and
      non-Hispanic black women should include information about both the technical
      aspects and the social value of donation. The specific terms "umbilical" and
      "donation" should be used consistently to prevent misunderstanding. Information
      should be provided by physicians with follow-up by other health providers.

PMID- 20051054
TI  - Removal by adsorbent beads of biological response modifiers released from
      platelets, accumulated during storage, and potentially associated with platelet
      transfusion reactions.
AB  - BACKGROUND: Recent studies have demonstrated that biological response modifiers
      (BRMs) released from platelets (PLTs) during storage may have a clinical
      significance in PLT transfusion reactions. Washing PLTs and partial substitution
      of plasma with artificial solutions reduce transfusion reactions, but the washing
      procedure is time-consuming, and partial plasma substitution is not sufficient to
      completely eliminate transfusion reactions. STUDY DESIGN AND METHODS: This study
      determined the levels of three BRMs: soluble CD40 ligand (sCD40L); regulated upon
      activation, normal T-cell expressed, and secreted (RANTES, CCL5); and
      transforming growth factor-beta1 (TGF-beta1). These BRMs were released from PLTs
      during storage up to Day 10. To selectively remove these BRMs, four types of
      cellulose beads were investigated. The levels of these three BRMs in plasma
      derived from PLT concentrates (PCs) stored for 10 days or in PCs stored for 5
      days were determined after treatment with or without each adsorbent bead for 3
      hours. RESULTS: These three BRMs accumulated in proportion to the storage
      duration. The 3-hour treatment with cellulose beads possessing sulfate ester
      groups (A) or phosphate ester groups (B) effectively removed sCD40L and RANTES
      and partly removed TGF-beta1. In addition, although PLT activation was minimally
      induced, PLT counts decreased by approximately 13% to 30%, after these
      treatments. CONCLUSIONS: This study revealed that Cellulose Beads A or B are
      effective in removing the three BRMs that accumulate during PLT storage.
      Additional in vitro assays and in vivo studies are required to evaluate whether
      this method is effective in reducing transfusion reactions.

PMID- 20051055
TI  - Preharvest hematopoietic progenitor cell counts predict CD34+ cell yields in
      granulocyte-colony-stimulating factor-mobilized peripheral blood stem cell
      harvest in healthy donors.
AB  - BACKGROUND: The hematopoietic progenitor cell (HPC) count measured by the Sysmex
      hematology analyzer can determine the timing for leukapheresis in autologous
      peripheral blood stem cell (PBSC) harvest. We evaluated whether a HPC count could
      predict CD34+ cell yield in healthy, unrelated donors after granulocyte-colony
      stimulating factor mobilization. STUDY DESIGN AND METHODS: A total of 117 healthy
      donors underwent 161 PBSC leukapheresis procedures in our institution. The HPCs
      and CD34+ cells were identified by an automated hematology analyzer and flow
      cytometry, respectively. Using Spearman's rank test, we evaluated the
      relationships between preharvest HPCs, CD34+ cell counts, and CD34+ cell yields
      in the apheresis product. A receiver operating characteristic (ROC) curve
      analysis was used to identify the cutoff value of HPC for adequate mobilization
      and harvest yield. RESULTS: The HPC count had a moderate correlation with the
      preharvest CD34+ cell count (r = 0.502, p < 0.001), and an HPC count of more than
      21.3 x 10(6)/L could exclude poor mobilization (<20 x 10(6) CD34+ cells/L) with
      sensitivity and specificity of 89.2 and 83.3%. However, the relationship between
      HPC count and CD34+ cell yield was not marked (r = 0.321, p < 0.001). The area
      under the curve for HPCs was significantly smaller than the preharvest CD34+ cell
      count on the ROC curve for predicting adequate harvest yield (>10 x 10(6) CD34+
      cells/L of processed blood volume, 0.678 vs. 0.850, p = 0.001). CONCLUSION:
      Although the preapheresis HPC count could predict mobilization in healthy donors
      before leukapheresis, it may not be a superior index for predicting CD34+ cell
      yield compared with the preharvest CD34+ cell count.

PMID- 20051056
TI  - Immunoglobulin M red blood cell alloantibodies are frequently adsorbed by rabbit
      erythrocyte stroma.
AB  - BACKGROUND: Rabbit erythrocyte stroma (RESt, Immucor) adsorption is often used to
      remove cold autoantibodies from patient samples to facilitate detection of
      underlying alloantibodies. However, reports in the literature show that
      adsorption of clinically significant alloantibodies can occur. A 2006 study by
      Storry and colleagues suggested that immunoglobulin (Ig)M antibodies are adsorbed
      by RESt regardless of antigen specificity. In our study, we further investigated
      the adsorption of IgM red blood cell alloantibodies by RESt. STUDY DESIGN AND
      METHODS: A total of 12 sera containing monoclonal IgM antibodies of various
      specificities (anti- D, -C, -c, -E, -e, -K, -Jk(b), and -S) and titers, which
      were all shown to exhibit only IgM reactivity after dithiothreitol treatment, and
      two sera with polyclonal IgG (anti-Fy(a) and -K) were all adsorbed by RESt.
      Titers of unadsorbed, once-adsorbed, and twice-adsorbed IgM and IgG antibodies
      were determined in parallel. RESULTS: Ten of the 12 monoclonal IgM samples showed
      significant (more than fourfold) reduction in titer after RESt adsorptions. Both
      of the polyclonal IgG samples tested showed insignificant (fourfold or less)
      reduction in titer. CONCLUSIONS: RESt is known to effectively remove IgM cold
      autoantibodies. Our results show that monoclonal IgM alloantibodies are also
      frequently adsorbed by RESt with significant reduction in titer. Adsorption is
      variable and some IgM alloantibodies are not adsorbed. Further studies may
      elucidate the effect of RESt adsorption on IgG alloantibodies. Caution is needed
      when RESt is employed to remove interferences by cold autoantibodies in
      pretransfusion testing, and the risk of missed IgM alloantibodies must be
      considered.

PMID- 20051057
TI  - Piperacillin-induced immune hemolysis: new cases and a concise review of the
      literature.
AB  - BACKGROUND: In this study, the data of eight new patients in conjunction with
      previously reported cases with piperacillin-induced immune hemolytic anemia
      (PIHA) are described. STUDY DESIGN AND METHODS: Five patients with cystic
      fibrosis and three patients with other disorders developed massive hemolysis
      after administration of piperacillin. Serologic tests were carried out using
      standard techniques. Tests for drug-dependent antibodies (ddab) were performed in
      the presence and absence of piperacillin and its ex vivo antigens (urine of
      patients treated with piperacillin). RESULTS: Hemolysis was acute and severe in
      all eight patients. The direct antiglobulin test was positive in all cases. Sera
      from four patients reacted with red blood cells (RBCs) in the presence of
      piperacillin as well as its ex vivo antigens. Sera from three patients showed
      positive reactivity with untreated RBCs in the presence of piperacillin, and the
      serum from the remaining patient was reactive only in the presence of
      piperacillin ex vivo antigens. Other patients with PIHA have been reported in the
      literature. Three of these patients also had cystic fibrosis. CONCLUSION: To date
      approximately 26 patients with PIHA have been described and at least eight of
      these patients had cystic fibrosis. It is unclear whether patients with cystic
      fibrosis might be susceptible in developing PIHA.

PMID- 20051058
TI  - Function of platelets in apheresis platelet concentrates and in patient blood
      after transfusion as assessed by Impact-R.
AB  - BACKGROUND: Platelet (PLT) transfusion is a mainstream therapy for preventing or
      treating bleeding episodes in patients with thrombocytopenia. The efficacy is
      usually estimated from the corrected count increment of PLTs after transfusion,
      which does not assess PLT function. We therefore evaluated PLT function in blood
      samples of patients with thrombocytopenia before and after transfusion. STUDY
      DESIGN AND METHODS: PLT function was assessed in 24 chemotherapy-treated patients
      and in the PLT concentrates (PCs) by the Impact-R (DiaMed). This device evaluates
      PLT adhesion and aggregation recorded as surface coverage (%) and size of
      aggregates (AS microm(2)). P-selectin expression was determined by flow
      cytometry. RESULTS: The PCs were stored for a median of 70 hours before
      transfusion. An analysis stratified by the median storage of PCs (<70 hr or >70
      hr) showed no differences in the SC, the AS, and P-selectin expression between
      these concentrates' groups. Transfusion resulted in an increase of adhering PLTs
      in the patients after transfusion. There were no differences in the AS and in P
      selectin expression before and after transfusion, but the AS increased after
      transfusion upon ex vivo exposure to adenosine 5'-diphosphate. P-selectin
      expression was significantly lower in the patient group receiving PCs stored for
      more than 70 hours. CONCLUSION: The current trial shows the feasibility of using
      the Impact-R to assess the function of transfused PLTs in the patient's blood
      stream.

PMID- 20051059
TI  - Is "transfusion-associated necrotizing enterocolitis" an authentic pathogenic
      entity?
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) sometimes occurs after a transfusion,
      but it is unclear whether this is a chance association or cause and effect. STUDY
      DESIGN AND METHODS: We compared features of neonates that developed surgical NEC
      within 48 hours after transfusion with others that developed NEC not preceded by
      transfusion. We assessed the blood used for transfusion and feeding practices
      among NEC cases and controls. RESULTS: Forty neonates developed surgical NEC
      after a transfusion and 72 developed NEC unrelated to a transfusion. Those with
      NEC after transfusion were born at earlier gestation (mean 27 weeks, 90%
      confidence interval [CI] 26-28 years vs. mean 30, 90% CI 29-31; p < 0.001) and
      were of lower birth weight (mean 981 g, 90% CI 835-1128 g vs. mean 1371 g, 90% CI
      1245-1496; p < 0.001) and developed NEC later during their neonatal intensive
      care unit course (day of life: mean 23, 90% CI 20-27 vs. mean 16, 90% CI 13-19; p
      < 0.001). Transfusions were more prevalent among those that developed NEC (p <
      0.001). The blood transfused to those that developed NEC was not older, but those
      who developed NEC had been fed larger volumes of milk in the 24 hours before and
      during transfusion (p = 0.04) and were more likely to have been fed a bovine
      product during that period (p = 0.004). CONCLUSION: Approximately one-third of
      surgical NEC cases in our system occurred after a transfusion. We speculate that
      a target area for reducing the prevalence of posttransfusion NEC involves feeding
      practices immediately before and during RBC transfusion.

PMID- 20051060
TI  - Protein quality in Mirasol pathogen reduction technology-treated, apheresis
      derived fresh-frozen plasma.
AB  - BACKGROUND: The Mirasol pathogen reduction technology (PRT) system for plasma is
      based on a riboflavin (vitamin B(2)) and ultraviolet (UV) light treatment process
      resulting in pathogen inactivation due to irreversible photo-oxidative damage of
      nucleic acids. The purpose of this study was to evaluate the in vitro protein
      quality of apheresis-derived plasma treated with riboflavin and UV light in
      comparison with untreated fresh-frozen plasma (FFP). STUDY DESIGN AND METHODS:
      Twenty apheresis plasma samples (270 + or - 10 mL) were combined with 35 + or - 5
      mL of riboflavin solution (500 microM), yielding a mean 60 microM final
      riboflavin concentration, and then exposed to UV light (6.24 J/mL). Riboflavin
      and UV light-treated plasma was then flash frozen, within 8 hours of collection,
      generating treated FFP. Treated FFP was thawed and analyzed using standard
      coagulation assays, and the percent retention of protein activity was reported,
      relative to untreated, paired controls. RESULTS: Plasma proteins demonstrated
      different sensitivities to riboflavin and UV treatment. The amount of total
      protein remained unchanged. After treatment, fibrinogen (antigen) showed 99%
      retention; Factor (F)XII, FXIII, ADAMTS-13, and von Willebrand factor (ristocetin
      cofactor) 96% to 100%. Fibrinogen retained 77% activity, FII 80%, FVIIIc 75%, and
      FV 73% after treatment. Antithrombin, protein S, plasminogen, and alpha(2)
      antiplasmin retained between 91 and 100% activity. CONCLUSION: The results from
      this study demonstrate that coagulant and anticoagulant proteins in riboflavin
      and UV light-treated (PRT) apheresis plasma are well preserved.

PMID- 20051061
TI  - Quality evaluation of frozen apheresis red blood cell storage with 21-day
      postthaw storage in additive solution 3 and saline-adenine-glucose-mannitol:
      biochemical and chromium-51 recovery measures.
AB  - BACKGROUND: The Czech Republic decided to build the frozen red blood cell (RBC)
      bank for military contingency and civil emergency preparedness. Storage methods
      were validated with (51)Cr recovery measures out to 21 days postthaw. STUDY
      DESIGN AND METHODS: A total of 139 apheresis RBC units collected in additive
      solution (additive solution 3 [AS-3] or saline-adenine-glucose-mannitol [SAG-M])
      were obtained from volunteers by double erythrocytapheresis; all were sterilely
      glycerolized, frozen, stored for at least 30 days at a minimum of -65 degrees C
      in collection or cryogenic bags, thawed, sterilely deglycerolized, and stored at
      4 +/- 2 degrees C for up to 21 days in AS-3 or SAG-M. Units were sampled before
      storage and after thaw weekly. Metabolic intermediates and (51)Cr recovery
      measures were obtained to determine the index of therapeutic effectiveness (ITE).
      RESULTS: Despite losses associated with cryoconservation and eventual transfer to
      cryogenic bags, 3-week storage with optimum ITE was obtained with frozen storage
      in primary collection or cryogenic bags and postthaw storage in AS-3. Such cells
      would pass as acceptable in vitro hematology and biochemistry variables.
      CONCLUSIONS: A system for frozen RBC storage with 3-week, postthaw, liquid
      storage has been validated. With commercially available components and automated
      processing, it is capable of supporting civilian rare blood and emergency and
      international military combat and peacekeeping support use patterns.

PMID- 20051062
TI  - Descending deep neck infection in a liver transplant patient.
AB  - Descending deep neck space infections are serious conditions that appear as a
      complication of cervical and odontogenic infections. Infecting bacteria descend
      into the mediastinum causing systemic toxicity and septic shock. Liver transplant
      patients are at increased risk of developing life-threatening infections, but
      reports about descending deep neck space infections in these patients are scarce.
      Here, we report a case of deep neck infection resulting in mediastinitis in a
      liver transplant patient. Streptococcus anginosus was isolated in blood cultures.

PMID- 20051063
TI  - Automated counting of nucleated cells in equine synovial fluid without and with
      hyaluronidase pretreatment.
AB  - BACKGROUND: Microscopy is usually used to obtain manual total and differential
      cell counts in equine synovial fluid. A faster, more precise method is desirable.
      OBJECTIVES: The objectives were to compare an automated impedance method with a
      manual method for obtaining total and differential cell counts in equine synovial
      fluid and to evaluate the effect of pretreatment with hyaluronidase on automated
      results. METHODS: Synovial fluid samples (n=48) were collected into EDTA and
      analyzed within 48 hours. Automated total and differential cell counts were
      evaluated using a Medonic CA620-VET hematology analyzer before and after
      pretreatment for 5-30 minutes with hyaluronidase (final concentration 0.01
      mg/mL). A hemacytometer count and microscopic evaluation of a direct smear were
      used as the reference method. Intra-assay coefficients of variation (CV) were
      determined. RESULTS: Thirty-one of 46 untreated samples and 0/46 hyaluronidase
      treated samples were error-flagged by the analyzer. Correlation between automated
      (ANCC) and manual (MNCC) nucleated cell counts in untreated samples (n=15;
      R(2)=0.93) and pretreated samples (n=46; R(2)=0.94) was high, and pseudomedian
      difference was low. Intra-assay CVs for samples with medium and high cellularity
      were significantly lower for ANCC (1.5-2.7%) compared with MNCC (6.1-15.7%)
      (P<.01). Valid automated differential cell counts were not obtained. CONCLUSIONS:
      Automated total cell counts obtained on the Medonic analyzer correlate well with
      manual counts in equine synovial fluid; however, pretreatment with hyaluronidase
      is required to minimize error flags. Automated differential counts are not
      accurate for synovial fluid.

PMID- 20051065
TI  - Special care dentistry on a global scale.

PMID- 20051064
TI  - Hematologic and biochemical reference intervals for Norwegian crossbreed grower
      pigs.
AB  - BACKGROUND: Hematologic and biochemical reference intervals depend on many
      factors, including environment and age. Reference intervals for Norwegian grower
      pigs are lacking, and previously published reference intervals for similar pigs
      from other countries are now outdated due to significant changes in management
      and breeding on the pig farms. OBJECTIVES: The aim of this study was to determine
      updated reference intervals for hematologic and biochemical analytes in healthy
      crossbred grower pigs, and to compare the results among 3 different farms.
      METHODS: Blood samples were collected from 104 clinically healthy pigs of the
      most common Norwegian crossbreed (Landrace Yorkshire sow x Landrace Duroc boar).
      The pigs were 12-16 weeks old, weighed 30-50 kg, of both sexes, and lived on 3
      farms in eastern Norway. Automated hematologic and biochemical analysis were
      performed using ADVIA 2120 and ADVIA 1650 analyzers. RESULTS: Five samples were
      excluded because of hemolysis (1) or outliers (4). Reference intervals were
      calculated using parametric or nonparametric methods, depending on data
      distribution. Mean, median, minimum, and maximum values were tabulated.
      CONCLUSIONS: The reference intervals calculated in this study will be useful for
      the diagnosis and monitoring of disease in this widespread crossbreed pig.
      Compared with previously published reference values, reference intervals for
      total WBC count, creatine kinase and alanine aminotransferase activities, and
      albumin, bilirubin, and urea concentrations in this study differed notably.

PMID- 20051067
TI  - Complications associated with anesthesia administration for dental treatment in a
      special needs clinic.
AB  - The goal of this study was to identify and quantify complications occurring with
      the administration of anesthesia for the dental treatment of patients with
      special needs. Anesthesia providers completed a standardized evaluation form,
      delineating possible complications for 202 consecutive ambulatory patients
      receiving anesthesia in a special needs clinic. Statistical analysis of four
      types of administered anesthesia showed that the overall complication rate was
      23.8%. Evaluation of the data showed complications that were considered either
      mild (95.8%), or moderate (4.2%), while no reports of severe complications
      occurred. Airway obstruction and nausea/vomiting were the most frequently
      encountered complications. Variables found to affect the incidence of anesthetic
      complications included ASA classification, anesthetic technique, Mallampati
      airway classification, and type of dental procedure performed. An evaluation of
      the results of the study showed that the majority of complications that occurred
      with anesthesia during care of patients with special needs were mild and did not
      lead to severe adverse events. Our findings show that anesthesia administered
      during dental treatment for patients with special needs is safe and effective.

PMID- 20051068
TI  - The self-reported oral health status and behaviors of adults who are deaf and
      blind.
AB  - This qualitative study explored perceived oral health, felt need, oral health
      knowledge and behaviors, and utilization of dental services among a community of
      deaf and blind adults in Toronto, Canada. Seven adults participated in in depth
      interviews facilitated by intervenors skilled in communication with people who
      are deaf and blind. Subjects reported that their oral health was good, however
      oral health knowledge was poor and daily oral hygiene practices were minimal. Few
      subjects had ever received dental health education and were largely unaware of
      how to prevent dental disease. A subsidized dental program enabled subjects to
      have regular dental visits, though they were concerned about the costs of more
      complex dental treatment not covered by the program. They also worried about
      finding an alternative source of care once their eligibility for the program
      ceased at the age of 65. The presence of the subsidized sympathetic dental
      program and the facilitative role of intervenors promoted utilization of dental
      care for many of the subjects who participated in this study. There is a clear
      need to develop appropriate dental health education programs for this group of
      people, which would harness the support of the community of deaf and blind people
      and their intervenors. The interventions need to be sensitive and appropriate for
      the individual's level of impairment.

PMID- 20051069
TI  - Hurler syndrome: a case report of a 5-year follow-up of dental findings after
      bone marrow transplantation.
AB  - Hurler syndrome is a rare autosomal recessive disorder of mucopolysaccharide
      metabolism. It results from a deficiency in lysosomal enzymes responsible for the
      breakdown of glycosaminoglycans. Affected individuals may show progressive
      physical and mental deterioration as glycosaminoglycans are deposited in the
      organs of the body. Bone marrow transplantation (BMT) is effective in improving
      some of the clinical manifestations of Hurler syndrome. Death is caused by
      cardiorespiratory failure and usually occurs before the second decade of life. In
      this case report, the course of dental development was followed over 5 years,
      from the primary dentition into the permanent dentition, of a child who was
      successfully treated with a bone marrow transplant in infancy. The timing of bone
      marrow therapy has significant and variable effect on the stages of tooth
      development with implications for the long-term maintenance of the dentition.

PMID- 20051070
TI  - An assessment of the dental health of chronic institutionalized patients with
      psychiatric disease in Israel.
AB  - Many institutionalized patients with psychiatric disease have been discharged
      into the community and the patients who remain hospitalized are at a particularly
      high risk for dental disease. This study assessed the oral health and treatment
      needs of chronically hospitalized patients with psychiatric disease in Israel. A
      random sample of 301 patients hospitalized for more than 1 year in 14 of 18
      psychiatric institutions in Israel was drawn from the National Psychiatric
      Hospitalization Registry, and 84.4% of them were examined. Their dental status
      was evaluated using decayed, missing, filled teeth (DMF-T) index and demographic
      and medical data were retrieved from the patients' files. Of the 254 patients
      examined, 4 (1.6%) were caries-free, 176 (69%) patients had only a partial
      natural dentition, while 66 (26%) were edentulous. The average DMF-T score was
      23.8. The caries component accounted for 2.7 of the DMF-T, the missing teeth
      component was 20, and the restored teeth component was only 1.1. There was a
      negative correlation between age and treated caries, and a positive correlation
      between age and missing teeth. Not all edentulous patients had dentures. These
      findings confirm the need to improve the oral health of chronic psychiatric
      inpatients and the need for dental treatment. The existing policy should be
      adjusted to integrate the currently separated delivery of the dental services for
      institutions and community settings. Dental professionals in the health service
      should be rewarded to restore teeth in this population rather than just to
      extract them.

PMID- 20051071
TI  - Recessive dystrophic epidermolysis bullosa--oral rehabilitation using
      stereolithography and immediate endosseous implants.
AB  - Dental management of patients with epi-dermolysis bullosa (EB) is challenging
      because of the severe soft tissue lesions associated with this disease. A case
      history is presented where two immediate endosseous implants were placed in the
      mandible of a patient with recessive dystrophic EB using computer-aided
      technology to plan the surgery and prosthetic rehabilitation. After a 24-month
      follow-up, the prosthesis was stable with healthy asymptomatic soft tissue around
      the implants. The stereolithographic model provides a precise and noninvasive
      copy of the mandibular and maxillary arches of patients with EB for
      rehabilitation of the dentition with immediate endosseous implants and a
      prosthesis.

PMID- 20051072
TI  - Occurrence of ameloblastoma in a patient with nasopharyngeal carcinoma after
      treatment by irradiation.
AB  - Ameloblastoma is the most common clinically significant epithelial odontogenic
      tumor, and is considered a benign but locally aggressive tumor of the
      craniofacial region. We present the case history of a 46-year-old male patient
      who had a nasopharyngeal carcinoma (NPC) treated by irradiation, which was
      complicated by the occurrence of an ameloblastoma. Following a review of the
      English language literature, this case history was identified as being the first
      report, to our knowledge, of the occurrence of ameloblastoma in a patient who had
      been irradiated for an NPC. This case report highlights the importance of regular
      dental care for a patient who had an NPC and was treated with radiation therapy.

PMID- 20051073
TI  - Keeping mental health promotion alive.

PMID- 20051074
TI  - Adherence according to Mary Poppins: strategies to make the medicine go down.
AB  - PURPOSE: This article reviews the prevalence, risk factors, and burden of
      nonadherence in mood and psychotic disorders, and presents evidence-based,
      disease-specific strategies shown to improve adherence. CONCLUSION: A
      comprehensive approach based on the goal of remission, designed around the
      patient's individual needs, facilitates adherence, leads to improved quality of
      life, and reduces disease burden. PRACTICE IMPLICATIONS: Adherence in mood and
      psychotic disorders can be improved when providers take time to build trusting
      relationships; identify risk factors; anticipate nonadherence; individualize
      treatment; and educate patients, families, and other healthcare providers.

PMID- 20051075
TI  - Prevalence of negative birth perception, disaffirmation, perinatal trauma
      symptoms, and depression among postpartum women.
AB  - PURPOSE: This study documented new case and estimated annual case prevalence, and
      relationships among women's negative birth perceptions, provider disaffirmation,
      perinatal trauma symptoms, and depression at 6-7 months postpartum. DESIGN AND
      METHODS: An exploratory investigation of 71 White women (20.8% of the total
      population) was conducted. CONCLUSIONS. New case prevalence of negative birth
      perceptions (9.6:100), perinatal trauma symptoms (10.2:100), disaffirmation
      (8.6:100), and depression (15.7:100) are greater than other prominent high burden
      diseases. Variables were significantly correlated. PRACTICE IMPLICATIONS:
      Findings reinforce the need for psychiatric liaison advanced practice nurses
      caring for childbearing women, including roles for detection/screening, educating
      professionals in communication, legislative/advocacy for funding, and further
      research.

PMID- 20051076
TI  - Biologic correlates to the development of post-traumatic stress disorder in
      female victims of intimate partner violence: implications for practice.
AB  - PURPOSE: The purpose of this article is to discuss the current literature about
      the risk of post-traumatic stress disorder (PTSD) in victims of intimate partner
      violence (IPV). CONCLUSIONS: PTSD is a complex and serious syndrome with
      emotional symptoms, psychiatric symptoms, and physical consequences. PTSD is
      associated with impaired immune function, obesity, increased risk of diabetes,
      increased severity of premenstrual syndrome symptoms, depression, suicide, and
      increased likelihood of re-abuse. Female victims of IPV develop PTSD and related
      consequences at a rate of 74-92%, compared to 6-13% in non-abused women. PRACTICE
      IMPLICATIONS: Advanced practice nurses (APNs) are likely to see one or both of
      these problems in their practices. The vague, nonspecific symptoms can present
      challenges to APNs. Biologic correlates are identified to help the APNs identify
      those most at risk of developing PTSD. Treatment options are discussed.

PMID- 20051077
TI  - Fathers, daughters, and anorexia nervosa.
AB  - PURPOSE: The study described the nature and meaning of the father-daughter
      relationship throughout the daughter's (N = 11) life from the perspective of the
      daughter, who has been in a 2-year recovery from anorexia nervosa (AN).
      Particular consideration was given to the changes over time. DESIGN AND METHODS:
      A narrative analysis method was used to examine the daughter's stories. FINDINGS:
      Several patterns emerged. This study is an exploration of the paths and processes
      that lead to, through, and into recovery from AN with regard to the father
      daughter relationship. PRACTICE IMPLICATIONS: The results have implications for
      nursing practice, research, and health policy.

PMID- 20051078
TI  - What community living problems do persons with schizophrenia report during
      periods of stability?
AB  - PURPOSE: This article describes problems reported by persons with schizophrenia
      while stable. DESIGN AND METHODS: This descriptive study followed 12 outpatients
      with at least 6 months without psychiatric hospitalization for 3 months in the
      community. FINDINGS. The most frequently reported problems were missed
      appointments and loneliness. Anxiety was the most commonly reported psychiatric
      symptom. No participant reported any psychotic symptoms, but participants
      reported conflict at home. PRACTICE IMPLICATIONS: Medication- and appointment
      adherence monitoring are ongoing priorities, as are the provision of
      interventions designed to support adherence. Stable persons with schizophrenia
      are poised to garner maximum benefit from support like family education and
      social skills training.

PMID- 20051079
TI  - Health consequences of childhood sexual abuse.
AB  - PURPOSE: This article provides a summary for advocacy, court testimony,
      assessment, treatment, prevention, and further research studies in the field of
      childhood sexual abuse. FINDINGS: A literature review identifies the psychiatric,
      social, and disease disorders to which this population is predisposed. Adult
      survivors experience more depression, obesity, autoimmune disorders (irritable
      bowel syndrome, asthma, fibromyalgia), eating disorders, and addictions. PRACTICE
      IMPLICATIONS: A holistic perspective allows understanding of health consequences
      for survivors. A model through which to consider these phenomena is presented.
      CONCLUSIONS: The long-term consequences of childhood sexual abuse must be
      assessed and addressed by healthcare professionals.

PMID- 20051080
TI  - Development and evaluation of a guideline for nursing care of suicidal patients
      with schizophrenia.
AB  - PURPOSE: The purpose of this study was to develop and test an evidence-based
      guideline that would support nursing care for suicidal patients with
      schizophrenia. DESIGN AND METHODS: Systematic review of the literature and
      consultation of experts preceded completion of the guideline. Twenty-one nurses
      from two mental health institutions tested the guideline for feasibility in
      nursing practice. FINDINGS: The guideline was found to support discussing
      suicidality with patients and assessing suicide risk. Participants endorsed
      implementation of the guideline in mental health care. PRACTICE IMPLICATIONS:
      Nurses who care for patients with schizophrenia are advised to use this guideline
      as a foundation for their care.

PMID- 20051081
TI  - Cultural competence: a systemic challenge to nursing education, knowledge
      exchange, and the knowledge development process.

PMID- 20051084
TI  - A complementary ecological model of the coordinated school health program.
AB  - BACKGROUND: A complementary ecological model of the coordinated school health
      program (CSHP) reflecting 20 years of evolved changes is proposed. Ecology refers
      to the complex interrelationship between intrapersonal factors, interpersonal
      processes and primary groups, institutional factors, community factors, and
      public policy. METHODS: Public health and child development theories that
      incorporate the influence of personal and social environments on health behavior,
      along with models that incorporate the influence of ecology, were consulted.
      RESULTS: Concepts from several models were combined with the 8 components of CSHP
      to formulate an ecological model involving 6 program and services components in
      an inner circle surrounded by 4 concentric rings representing the healthy school
      environment, essential structures of CSHP, local school district governance, and
      family and community involvement. CONCLUSION: This complementary ecological model
      is intended to serve as an additional conceptual approach to CSHP practice,
      evaluation, and research, and should prove especially useful to practitioners and
      researchers who already have a fundamental understanding of CSHP.

PMID- 20051085
TI  - An ecological model of the coordinated school health program: a commentary.

PMID- 20051086
TI  - Obesity prevention in early adolescence: student, parent, and teacher views.
AB  - BACKGROUND: Obesity is a significant health problem among today's youth; however,
      most school-based prevention programs in this area have had limited success.
      Focus groups were conducted with seventh- to eighth-grade students, parents, and
      teachers to provide insight into the development of a comprehensive program for
      the prevention of adolescent obesity: the Teen Eating and Activity Mentoring in
      Schools project (TEAMS). METHODS: Questions addressed (1) beliefs about the
      relationship between early adolescent behavior and health; (2) early adolescents'
      physical activity habits, preferences, influences, and barriers; (3) early
      adolescents' dietary habits, preferences, influences, and barriers; and (4)
      recommendations for interventions to promote physical activity and healthy eating
      in early adolescence. RESULTS: Qualitative analyses revealed that early
      adolescents had a good understanding of the relationship between their behavior
      and their health, although they had a limited understanding of what constitutes
      healthy eating. Youth participants reported preferences for a number of healthy
      foods and physical activities, but identified numerous barriers preventing their
      engagement. The major difference between students, parents, and teachers
      reflected the operation of the fundamental attribution error with early
      adolescents attributing their unhealthy behaviors to situational factors,
      teachers blaming parents, and parents blaming their children. CONCLUSIONS:
      Implications of these findings for the development of school-based, integrated
      strategies for obesity prevention among early adolescents are discussed.

PMID- 20051087
TI  - Individual, family, and community environmental correlates of obesity in Latino
      elementary school children.
AB  - BACKGROUND: The prevalence of overweight children has reached epidemic
      proportions, and affects Latinos youth more than other subgroups in the United
      States. Given the prevalence of obesity and its economic consequences, community
      health initiatives have shifted toward primary prevention at younger ages.
      METHODS: Data representing all levels of the ecological systems theory were
      collected using diverse methods. Participants were children enrolled in K-2nd
      grade and their parents. RESULTS: Overweight children were less active compared
      to normal weight children. The parents of overweight children provided less
      instrumental support to engage in activity and set fewer limits on their child's
      activities. Similarly, parents of overweight children were less likely to
      control, but more likely to set limits on their child's diet compared to parents
      of normal weight children. Parents who rated their health more positively and
      were less acculturated were more likely to have children who were overweight.
      School and community level variables were not significantly correlated with
      children's weight. Adjusting for the aforementioned variables, parents' weight
      status was positively associated with children's weight. CONCLUSIONS: Social and
      structural environments in which Hispanic children are reared may play an
      important role in determining their risk for obesity and related behaviors.
      Parents' weight was among the strongest correlate of child weight; however, the
      extent to which this influence functions primarily through biological or
      social/structural influences is not entirely clear. The role of school and
      community factors on child's health practices and body mass index needs to be
      further examined.

PMID- 20051088
TI  - Physical activity and sports team participation: associations with academic
      outcomes in middle school and high school students.
AB  - BACKGROUND: Previous studies have found that higher physical activity levels are
      associated with greater academic achievement among students. However, it remains
      unclear whether associations are due to the physical activity itself or sports
      team participation, which may involve requirements for maintaining certain
      grades, for example. The purpose of this study is to examine the associations
      between sports team participation, physical activity, and academic outcomes in
      middle and high school students. METHODS: Data were drawn from Project EAT
      (Eating Among Teens), a survey of middle and high school students (n = 4746).
      Students self-reported their weekly hours of physical activity, sports team
      participation, and academic letter grades. Two statistical models were
      considered: first, 2 separate regression analyses with grade point average (GPA)
      as the outcome and either sports team participation or physical activity as the
      predictor; second, a single regression with GPA as the outcome and both sports
      team participation and physical activity as the simultaneous predictors. RESULTS:
      For high school girls, both physical activity and sports team participation were
      each independently associated with a higher GPA. For high school boys, only
      sports team participation was independently associated with a higher GPA. For
      middle school students, the positive association between physical activity and
      GPA could not be separated from the relationship between sports team
      participation and a higher GPA. CONCLUSIONS: Regardless of whether academic
      success was related to the physical activity itself or to participation on sports
      teams, findings indicated positive associations between physical activity
      involvement and academic achievement among students.

PMID- 20051089
TI  - Academic achievement and adolescent drug use: an examination of reciprocal
      effects and correlated growth trajectories.
AB  - BACKGROUND: The primary aim was to examine correlated growth trajectories and
      reciprocal effects between academic achievement and drug use over the course of
      junior high school. METHODS: One hundred and three male and 98 female students
      from 3 rural junior high schools were surveyed 4 times over the course of 3
      years. Dual trajectory latent growth models were estimated. RESULTS: Growth
      trajectories of school achievement and drug use over the course of junior high
      were highly correlated. Students who demonstrated deteriorating achievement
      during the course of junior high school showed an increase in drug use during
      this same time frame. Cross-process regressions indicated that students who
      demonstrated superior academic achievement in sixth grade exhibited a shallower
      rate of increase in drug use (ie, their drug use escalated to a lesser extent).
      CONCLUSIONS: The processes of academic disengagement (as marked by deteriorating
      grades) and drug use during adolescence appear to be related to one another.
      Prevention initiatives aimed at keeping adolescents academically engaged in
      school may have protective benefits against escalation of drug use.

PMID- 20051090
TI  - Integrating the revised asthma guidelines into school nursing scope and standards
      of practice.

PMID- 20051094
TI  - Wound cleansing, topical antiseptics and wound healing.
AB  - Quality of care is a critical requirement for wound healing and 'good' care of
      wounds has been synonymous with topical prevention and management of microbial
      contamination. Topical antiseptics are antimicrobial agents that kill, inhibit or
      reduce the number of microorganisms and are thought to be essential for wounds
      infection control. However, they have long and commonly been used on wounds to
      prevent or treat infection, the merits of antiseptic fluid irrigation have
      received little scientific study. Unlike antibiotics that act selectively on a
      specific target, antiseptics have multiple targets and a broader spectrum of
      activity, which include bacteria, fungi, viruses, protozoa and even prions.
      Although certain skin and wound cleansers are designed as topical solutions with
      varying degrees of antimicrobial activity, concerns have been raised. Wound
      cleansers may affect normal human cells and may be antimitotic adversely
      affecting normal tissue repair. Repeated and excessive treatment of wounds with
      antiseptics without proper indications may have negative outcomes or promote a
      microenvironment similar to those found in chronic wounds. However, when applied
      at the proper times and concentrations, some classes of antiseptics may provide a
      tool for the clinician to drive the wound bed in desired directions. The present
      review summarises the various antiseptics in use and their negative impact on the
      wound healing mechanisms. It is clear that the role of antiseptics on wounds and
      their role in wound care management need to be reconsidered.

PMID- 20051096
TI  - Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and
      laser confocal microscopy: type I and III collagens.
AB  - Although dermal collagens appear increased in hypertrophic scars, this has not
      been tested in tissue samples using objective methods. We compared the expression
      of types I and III collagen in hypertrophic and non hypertrophic scars at 6-12
      and 18-24 months after burn using a quantitative method. Among 17 patients with
      extensive burns, 3 patients had acute scars, 8 had hypertrophic or non
      hypertrophic scars at 6-12 months after burn and 6 had hypertrophic or non
      hypertrophic scars at 18-24 months after burn. After clinical assessment of scars
      using the Vancouver scale, immunohistochemistry for types I and III collagens was
      performed. Images were captured with a laser scanning confocal microscope and the
      relative amounts of types I and III collagens were determined in superficial and
      deep dermis. The effects of time and scar type were assessed using two-way
      analysis of variance (ANOVA) and Tukey's test. Collagen III scar/normal ratios
      were higher in hypertrophic scars at both time points (P = 0.05). There were no
      differences in collagen I scar/normal ratios. Large variation was observed in
      scars during the acute phase regarding the expression of collagens. Easily
      accessed by immunohistochemistry and confocal microscopy, type III collagen
      deposition may help in determining scar phenotype, differentiating hypertrophic
      and non hypertrophic scars.

PMID- 20051097
TI  - A clinical investigation into the microbiological status of 'locally infected'
      leg ulcers.
AB  - The complex interactions between patients and the microbial species that reside
      in their wounds are not yet fully characterised. Investigations to date have
      dealt with either those organisms that cause infections or those that establish
      long-term colonisations. The objective of this open, prospective pilot study was
      to quantitatively and qualitatively assess the microbiological status of 'locally
      infected' venous leg ulcers. Three different sampling techniques were used to
      recover organisms from 20 venous leg ulcers that had failed to progress towards
      healing and comparisons made to explore the distribution of colonised flora
      within the wound. In total, 116 isolates were recovered (mean of 5.8 per ulcer)
      with highest recovery rates seen with swabs. Greatest agreement of colonisation
      and counts was found between swabs and absorbent polyvinyl acetate (PVA) foam
      disc, and also between PVA discs and biopsies. Lowest agreement was between the
      distribution of anaerobes and coryneforms in swabs and biopsies, suggesting
      uneven vertical distribution within ulcers. No justification for using routine
      biopsies in locally infected venous leg ulcers was found.

PMID- 20051098
TI  - Dignity's wooly uplift.

PMID- 20051099
TI  - Placental thrombomodulin expression in recurrent miscarriage.
AB  - BACKGROUND: Early pregnancy loss can be associated with trophoblast insufficiency
      and coagulation defects. Thrombomodulin is an endothelial-associated
      anticoagulant protein involved in the control of hemostasis and inflammation at
      the vascular beds and it's also a cofactor of the protein C anticoagulant
      pathway. DISCUSSION: We evaluate the Thrombomodulin expression in placental
      tissue from spontaneous recurrent miscarriage and voluntary abortion as controls.
      Thrombomodulin mRNA was determined using real-time quantitative polymerase chain
      reaction. Reduced expression levels of thrombomodulin were found in recurrent
      miscarriage group compared to controls (1.82-fold of reduction), that corresponds
      to a reduction of 45% (from control group Delta CT) of thrombomodulin expression
      in spontaneous miscarriage group respect the control groups. SUMMARY: We cannot
      state at present the exact meaning of a reduced expression of Thrombomodulin in
      placental tissue. Further studies are needed to elucidate the biological pathway
      of this important factor in the physiopathology of the trophoblast and in
      reproductive biology.

PMID- 20051095
TI  - Intra-lesional injections of recombinant human epidermal growth factor promote
      granulation and healing in advanced diabetic foot ulcers: multicenter,
      randomised, placebo-controlled, double-blind study.
AB  - A multicenter, double-blind, placebo-controlled trial was carried out to evaluate
      the intra-lesional infiltration of recombinant epidermal growth factor (EGF) in
      Wagner's grade 3 or 4 diabetic foot ulcers (DFUs). Subjects (149) were randomised
      to receive EGF (75 or 25 microg) or placebo, three times per week for 8 weeks and
      standard good wound care. The main endpoint was granulation tissue covering > or
      = 50% of the ulcer at 2 weeks. It was achieved by 19/48 controls versus 44/53 in
      the 75 microg group [odds ratio (OR): 7.5; 95% confidence interval (CI): 2.9
      18.9] and 34/48 in the 25 microg group (OR: 3.7; 1.6-8.7). Secondary outcome
      variables such as end-of-treatment complete granulation response (28/48 controls,
      46/53 with 75 microg and 34/48 with 25 microg EGF), time-to-complete response
      (controls: 5 weeks; both EGF dose groups: 3 weeks), and wound closure after
      follow-up (25/48 controls, 40/53 with 75 microg and 25/48 with 25 microg EGF)
      were also treatment dependent. Multivariate analyses yielded that they were
      significantly enhanced by 75 microg EGF treatment and neuropathic versus ischemic
      ulcers. Most adverse events were mild and no drug-related severe adverse
      reactions were reported. It was concluded that recombinant human EGF (rhEGF)
      local injections offer a favourable risk-benefit balance in patients with
      advanced DFU.

PMID- 20051100
TI  - IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast
      and lung cancer patients.
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-I) signalling is important for
      cancer initiation and progression. Given the emerging evidence for the role of
      the stroma in these processes, we aimed to characterize the effects of IGF-I on
      cancer cells and stromal cells separately. METHODS: We used an ex vivo culture
      model and measured gene expression changes after IGF-I stimulation with cDNA
      microarrays. In vitro data were correlated with in vivo findings by comparing the
      results with published expression datasets on human cancer biopsies. RESULTS:
      Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show
      some common and other distinct response patterns. Among the up-regulated genes in
      the stromal fibroblasts we observed a significant enrichment in proliferation
      associated genes. The expression of the IGF-I induced genes was coherent and it
      provided a basis for the segregation of the patients into two groups. Patients
      with tumours with highly expressed IGF-I induced genes had a significantly lower
      survival rate than patients whose tumours showed lower levels of IGF-I induced
      gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset).
      Furthermore, based on an IGF-I induced gene expression signature derived from
      primary lung fibroblasts, a separation of prognostically different lung cancers
      was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset).
      CONCLUSION: Expression patterns of genes induced by IGF-I in primary breast and
      lung fibroblasts accurately predict outcomes in breast and lung cancer patients.
      Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts
      might be promising predictors for the response to IGF-I targeted therapies. See
      the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741
      7015/8/2.

PMID- 20051101
TI  - Basic and clinical significance of IGF-I-induced signatures in cancer.
AB  - The insulin-like growth factor (IGF) system mediates growth, differentiation and
      developmental processes; it is also involved in various metabolic activities.
      Deregulation of IGF system expression and action is linked to diverse
      pathologies, ranging from growth deficits to cancer development. Targeting of the
      IGF axis emerged in recent years as a promising therapeutic approach in cancer
      and other medical conditions. Rational use of IGF-I-induced gene signatures may
      help to identify patients who might benefit from IGF axis-directed therapeutic
      modalities. In the accompanying research article in BMC Medicine, Rajski et al.
      show that IGF-I-induced gene expression in primary breast and lung fibroblasts
      accurately predict outcomes in breast and lung cancer patients.See the associated
      research paper by Rajski et al: http://www.biomedcentral.com/1741-7015/8/1.

PMID- 20051102
TI  - Epithelial-mesenchymal transition in primary human bronchial epithelial cells is
      Smad-dependent and enhanced by fibronectin and TNF-alpha.
AB  - BACKGROUND: Defective epithelial repair, excess fibroblasts and myofibroblasts,
      collagen overproduction and fibrosis occur in a number of respiratory diseases
      such as asthma, chronic obstructive pulmonary disease (COPD) and pulmonary
      fibrosis. Pathological conversion of epithelial cells into fibroblasts
      (epithelial-mesenchymal transition, EMT) has been proposed as a mechanism for the
      increased fibroblast numbers and has been demonstrated to occur in lung alveolar
      epithelial cells. Whether other airway cell types also have the capability to
      undergo EMT has been less explored so far. A better understanding of the full
      extent of EMT in airways, and the underlying mechanisms, can provide important
      insights into airway disease pathology and enable the development of new
      therapies. The main aim of this study was to test whether primary human bronchial
      epithelial cells are able to undergo EMT in vitro and to investigate the effect
      of various profibrotic factors in the process. RESULTS: Our data demonstrate that
      primary human bronchial epithelial cells (HBECs) are able to undergo EMT in
      response to transforming growth factor-beta 1 (TGF-beta1), as revealed by typical
      morphological alterations and EMT marker progression at the RNA level by real
      time quantitative polymerase chain reaction and, at the protein level, by western
      blot. By using pharmacological inhibitors we show that this is a Smad-dependent
      mechanism and is independent of extracellular signal-related kinase pathway
      activation. Additional cytokines and growth factors such as tumour necrosis
      factor-alpha (TNF-alpha), interleukin-1 beta (IL1beta) and connective tissue
      growth factor (CTGF) were also tested, alone or in combination with TGF-beta1.
      TNF-alpha markedly enhances the effect of TGF-beta1 on EMT, whereas IL1beta shows
      only a very weak effect and CTGF has no significant effect. We have also found
      that cell-matrix contact, in particular to fibronectin, an ECM component
      upregulated in fibrotic lesions, potentiates EMT in both human alveolar
      epithelial cells and HBECs. Furthermore, we also show that the collagen discoidin
      domain receptor 1 (DDR1), generally expressed in epithelial cells, is
      downregulated during the EMT of bronchial epithelium whereas DDR2 is unaffected.
      Our results also suggest that bone morphogenetic protein-4 is likely to have a
      context dependent effect during the EMT of HBECs, being able to induce the
      expression of EMT markers and, at the same time, to inhibit TGF-beta induced
      epithelial transdifferentiation. CONCLUSIONS: The results presented in this study
      provide additional insights into EMT, a potentially very important mechanism in
      fibrogenesis. We show that, in addition to alveolar epithelial type II cells,
      primary HBECs are also able to undergo EMT in vitro upon TGF-beta1 stimulation
      via a primarily Smad 2/3 dependent mechanism. The effect of TGF-beta1 is
      potentiated on fibronectin matrix and in the presence of TNF-alpha, representing
      a millieu reminiscent of fibrotic lesions. Our results can contribute to a better
      understanding of lung fibrosis and to the development of new therapeutic
      approaches.

PMID- 20051103
TI  - Do consumers' preferences for improved provision of malaria treatment services
      differ by their socio-economic status and geographic location? A study in
      southeast Nigeria.
AB  - BACKGROUND: Improvement of utilization of malaria treatment services will depend
      on provision of treatment services that different population groups of consumers
      prefer and would want to use. Treatment of malaria in Nigeria is still
      problematic and this contributes to worsening burden of the disease in the
      country. Therefore this study explores the socio-economic and geographic
      differences in consumers' preferences for improved treatment of malaria in
      Southeast Nigeria and how the results can be used to improve the deployment of
      malaria treatment services. METHODS: This study was undertaken in Anambra state,
      Southeast Nigeria in three rural and three urban areas. A total of 2,250 randomly
      selected householders were interviewed using a pre tested interviewer
      administered questionnaire. Preferences were elicited using both a rating scale
      and ranking of different treatment provision sources by the respondents. A socio
      economic status (SES) index was used to examine for SES differences, whilst urban
      rural comparison was used to examine for geographic differences, in preferences.
      RESULTS: The most preferred source of provision of malaria treatment services was
      public hospitals (30.5%), training of mothers (19%) and treatment in Primary
      healthcare centres (18.1%). Traditional healers (4.8%) and patent medicine
      dealers (4.2%) were the least preferred strategies for improving malaria
      treatment. Some of the preferences differed by SES and by a lesser extent, the
      geographic location of the respondents. CONCLUSION: Preferences for provision of
      improved malaria treatment services were influenced by SES and by geographic
      location. There should be re-invigoration of public facilities for appropriate
      diagnosis and treatment of malaria, in addition to improving the financial and
      geographic accessibility of such facilities. Training of mothers should be
      encouraged but home management will not work if the quality of services of patent
      medicine dealers and pharmacy shops where drugs for home management are purchased
      are not improved. Therefore, there is the need for a holistic improvement of
      malaria treatment services.

PMID- 20051104
TI  - The B chromosomes of the African cichlid fish Haplochromis obliquidens harbour
      18S rRNA gene copies.
AB  - BACKGROUND: Diverse plant and animal species have B chromosomes, also known as
      accessory, extra or supernumerary chromosomes. Despite being widely distributed
      among different taxa, the genomic nature and genetic behavior of B chromosomes
      are still poorly understood. RESULTS: In this study we describe the occurrence of
      B chromosomes in the African cichlid fish Haplochromis obliquidens. One or two
      large B chromosome(s) occurring in 39.6% of the analyzed individuals (both male
      and female) were identified. To better characterize the karyotype and assess the
      nature of the B chromosomes, fluorescence in situ hybridization (FISH) was
      performed using probes for telomeric DNA repeats, 18S and 5S rRNA genes, SATA
      centromeric satellites, and bacterial artificial chromosomes (BACs) enriched in
      repeated DNA sequences. The B chromosomes are enriched in repeated DNAs,
      especially non-active 18S rRNA gene-like sequences. CONCLUSION: Our results
      suggest that the B chromosome could have originated from rDNA bearing
      subtelo/acrocentric A chromosomes through formation of an isochromosome, or by
      accumulation of repeated DNAs and rRNA gene-like sequences in a small proto-B
      chromosome derived from the A complement.

PMID- 20051105
TI  - THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic
      primitive cell survival in vivo.
AB  - BACKGROUND: The transcription/export complex is evolutionarily conserved from
      yeast to man and is required for coupled transcription elongation and nuclear
      export of mRNAs. FMIP(Fms interacting protein) is a member of the THO
      (suppressors of the transcriptional defects of hpr1delta by overexpression)
      complex which is a subcomplex of the transcription/export complex. THO complex
      (THOC) components are not essential for bulk poly (A)+ RNA export in higher
      eukaryotes, but for the nuclear export of subset of mRNAs, however, their exact
      role is still unclear. RESULTS: To study the role of THOC5/Fms interacting
      protein in vivo, we generated THOC5/Fms interacting protein knockout mice. Since
      these mice are embryonic lethal, we then generated interferon inducible
      conditional THOC5/Fms interacting protein knockout mice. After three poly
      injections all of the mice died within 14 days. No pathological alterations,
      however, were observed in liver, kidney or heart. Thus we considered the
      hematopoietic system and found that seven days after poly injection, the number
      of blood cells in peripheral blood decreased drastically. Investigation of bone
      marrow cells showed that these became apoptotic within seven days after poly
      injection. Committed myeloid progenitor cells and cells with long term
      reconstituting potential were lost from bone marrow within four days after poly
      injection. Furthermore, infusion of normal bone marrow cells rescued mice from
      death induced by loss of THOC5/Fms interacting protein. CONCLUSION: THOC5/Fms
      interacting protein is an essential element in the maintenance of hematopoiesis.
      Furthermore, mechanistically depletion of THOC5/Fms interacting protein causes
      the down-regulation of its direct interacting partner, THOC1 which may contribute
      to altered THO complex function and cell death.

PMID- 20051106
TI  - Non-invasive evaluation of nigrostriatal neuropathology in a proteasome inhibitor
      rodent model of Parkinson's disease.
AB  - BACKGROUND: Predominantly, magnetic resonance imaging (MRI) studies in animal
      models of Parkinson's disease (PD) have focused on alterations in T2 water 1H
      relaxation or 1H MR spectroscopy (MRS), whilst potential morphological changes
      and their relationship to histological or behavioural outcomes have not been
      appropriately addressed. Therefore, in this study we have utilised MRI to scan in
      vivo brains from rodents bearing a nigrostriatal lesion induced by intranigral
      injection of the proteasome inhibitor lactacystin. RESULTS: Lactacystin induced
      parkinsonian-like behaviour, characterised by impaired contralateral forelimb
      grip strength and increased contralateral circling in response to apomorphine. T2
      weighted MRI, 3-weeks post-lesion, revealed significant morphological changes in
      PD-relevant brain areas, including the striatum and ventral midbrain in addition
      to a decrease in T2 water 1H relaxation in the substantia nigra (SN), but not the
      striatum. Post-mortem histological analyses revealed extensive dopaminergic
      neuronal degeneration and alpha-synuclein aggregation in the SN. However,
      extensive neuronal loss could also be observed in extra-nigral areas, suggesting
      non-specific toxicity of lactacystin. Iron accumulation could also be observed
      throughout the midbrain reflecting changes in T2. Importantly, morphological, but
      not T2 relaxivity changes, were significantly associated with both behavioural
      and histological outcomes in this model. CONCLUSIONS: A pattern of morphological
      changes in lactacystin-lesioned animals has been identified, as well as
      alterations in nigral T2 relaxivity. The significant relationship of
      morphological changes with behavioural and histological outcomes in this model
      raises the possibility that these may be useful non-invasive surrogate markers of
      nigrostriatal degeneration in vivo.

PMID- 20051107
TI  - Molecular characterization of Legionella pneumophila-induced interleukin-8
      expression in T cells.
AB  - BACKGROUND: Legionella pneumophila is the causative agent of human Legionnaire's
      disease. During infection, the bacterium invades macrophages and lung epithelial
      cells, and replicates intracellularly. However, little is known about its
      interaction with T cells. We investigated the ability of L. pneumophila to infect
      and stimulate the production of interleukin-8 (IL-8) in T cells. The objective of
      this study was to assess whether L. pneumophila interferes with the immune system
      by interacting and infecting T cells. RESULTS: Wild-type L. pneumophila and
      flagellin-deficient Legionella, but not L. pneumophila lacking a functional type
      IV secretion system Dot/Icm, replicated in T cells. On the other hand, wild-type
      L. pneumophila and Dot/Icm-deficient Legionella, but not flagellin-deficient
      Legionella or heat-killed Legionella induced IL-8 expression. L. pneumophila
      activated an IL-8 promoter through the NF-kappaB and AP-1 binding regions. Wild
      type L. pneumophila but not flagellin-deficient Legionella activated NF-kappaB,
      p38 mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and
      transforming growth factor beta-associated kinase 1 (TAK1). Transfection of
      dominant negative mutants of IkappaBalpha, IkappaB kinase, NF-kappaB-inducing
      kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8
      activation. Inhibitors of NF-kappaB, p38 MAPK, and JNK blocked L. pneumophila
      induced IL-8 expression. In addition, c-Jun, JunD, cyclic AMP response element
      binding protein, and activating transcription factor 1, which are substrates of
      p38 MAPK and JNK, bound to the AP-1 site of the IL-8 promoter. CONCLUSIONS: Taken
      together, L. pneumophila induced a flagellin-dependent activation of TAK1, p38
      MAPK, and JNK, as well as NF-kappaB and AP-1, which resulted in IL-8 production
      in human T cells, presumably contributing to the immune response in Legionnaire's
      disease.

PMID- 20051108
TI  - Corynebacterium diphtheriae invasion-associated protein (DIP1281) is involved in
      cell surface organization, adhesion and internalization in epithelial cells.
AB  - BACKGROUND: Corynebacterium diphtheriae, the causative agent of diphtheria, is
      well-investigated in respect to toxin production, while little is known about C.
      diphtheriae factors crucial for colonization of the host. In this study, we
      investigated the function of surface-associated protein DIP1281, previously
      annotated as hypothetical invasion-associated protein. RESULTS: Microscopic
      inspection of DIP1281 mutant strains revealed an increased size of the single
      cells in combination with an altered less club-like shape and formation of chains
      of cells rather than the typical V-like division forms or palisades of growing C.
      diphtheriae cells. Cell viability was not impaired. Immuno-fluorescence
      microscopy, SDS-PAGE and 2-D PAGE of surface proteins revealed clear differences
      of wild-type and mutant protein patterns, which were verified by atomic force
      microscopy. DIP1281 mutant cells were not only altered in shape and surface
      structure but completely lack the ability to adhere to host cells and
      consequently invade these. CONCLUSIONS: Our data indicate that DIP1281 is
      predominantly involved in the organization of the outer surface protein layer
      rather than in the separation of the peptidoglycan cell wall of dividing
      bacteria. The adhesion- and invasion-negative phenotype of corresponding mutant
      strains is an effect of rearrangements of the outer surface.

PMID- 20051109
TI  - Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-kappaB pathway in
      carcinoma cells by inhibiting IKK phosphorylation.
AB  - BACKGROUND: The Epstein-Barr virus (EBV)-encoded EBNA1 protein is expressed in
      all EBV-associated tumours, including undifferentiated nasopharyngeal carcinoma
      (NPC), where it is indispensable for viral replication, genome maintenance and
      viral gene expression. EBNA1's transcription factor-like functions also extend to
      influencing the expression of cellular genes involved in pathways commonly
      dysregulated during oncogenesis, including elevation of AP-1 activity in NPC cell
      lines resulting in enhancement of angiogenesis in vitro. In this study we sought
      to extend these observations by examining the role of EBNA1 upon another pathway
      commonly deregulated during carcinogenesis; namely NF-kappaB. RESULTS: In this
      report we demonstrate that EBNA1 inhibits the canonical NF-kappaB pathway in
      carcinoma lines by inhibiting the phosphorylation of IKKalpha/beta. In agreement
      with this observation we find a reduction in the phosphorylation of IkappaBalpha
      and reduced phosphorylation and nuclear translocation of p65, resulting in a
      reduction in the amount of p65 in nuclear NF-kappaB complexes. Similar effects
      were also found in carcinoma lines infected with recombinant EBV and in the EBV
      positive NPC-derived cell line C666-1. Inhibition of NF-kappaB was dependent upon
      regions of EBNA1 essential for gene transactivation whilst the interaction with
      the deubiquitinating enzyme, USP7, was entirely dispensable. Furthermore, in
      agreement with EBNA1 inhibiting p65 NF-kappaB we demonstrate that p65 was
      exclusively cytoplasmic in 11 out of 11 NPC tumours studied. CONCLUSIONS:
      Inhibition of p65 NF-kappaB in murine and human epidermis results in tissue
      hyperplasia and the development of squamous cell carcinoma. In line with this,
      p65 knockout fibroblasts have a transformed phenotype. Inhibition of p65 NF
      kappaB by EBNA1 may therefore contribute to the development of NPC by inducing
      tissue hyperplasia. Furthermore, inhibition of NF-kappaB is employed by viruses
      as an immune evasion strategy which is also closely linked to oncogenesis during
      persistent viral infection. Our findings therefore further implicate EBNA1 in
      playing an important role in the pathogenesis of NPC.

PMID- 20051110
TI  - Adaptation and validation of the Charlson Index for Read/OXMIS coded databases.
AB  - BACKGROUND: The Charlson comorbidity index is widely used in ICD-9 administrative
      data, however, there is no translation for Read/OXMIS coded data despite
      increasing use of the General Practice Research Database (GPRD). Our main
      objective was to translate the Charlson index for use with Read/OXMIS coded data
      such as the GPRD and test its association with mortality. We also aimed to
      provide a version of the comorbidity index for other researchers using similar
      datasets. METHODS: Two clinicians translated the Charlson index into Read/OXMIS
      codes. We tested the association between comorbidity score and increased
      mortality in 146 441 patients from the GPRD using proportional hazards models.
      RESULTS: This Read/OXMIS translation of the Charlson index contains 3156 codes.
      Our validation showed a strong positive association between Charlson score and
      age. Cox proportional models show a positive increasing association with
      mortality and Charlson score. The discrimination of the logistic regression model
      for mortality was good (AUC = 0.853). CONCLUSION: We have translated a commonly
      used comorbidity index into Read/OXMIS for use in UK primary care databases. The
      translated index showed a good discrimination in our study population. This is
      the first study to develop a co-morbidity index for use with the Read/OXMIS
      coding system and the GPRD. A copy of the co-morbidity index is provided for
      other researchers using similar databases.

PMID- 20051111
TI  - Effects of alfa-hydroxy-isocaproic acid on body composition, DOMS and performance
      in athletes.
AB  - BACKGROUND: Alfa-Hydroxy-isocaproic acid (HICA) is an end product of leucine
      metabolism in human tissues such as muscle and connective tissue. According to
      the clinical and experimental studies, HICA can be considered as an anti
      catabolic substance. The present study investigated the effects of HICA
      supplementation on body composition, delayed onset of muscle soreness (DOMS) and
      physical performance of athletes during a training period. METHODS: Fifteen
      healthy male soccer players (age 22.1+/-3.9 yr) volunteered for the 4-week double
      blind study during an intensive training period. The subjects in the group HICA
      (n = 8) received 583 mg of sodium salt of HICA (corresponding 500 mg of HICA)
      mixed with liquid three times a day for 4 weeks, and those in the group PLACEBO
      (n = 7) received 650 mg of maltodextrin mixed with liquid three times a day for
      the same period. According to a weekly training schedule, they practiced soccer 3
      - 4 times a week, had strength training 1 - 2 times a week, and had one soccer
      game during the study. The subjects were required to keep diaries on training,
      nutrition, and symptoms of DOMS. Body composition was evaluated with a dual
      energy X-ray absorptiometry (DXA) before and after the 4-week period. Muscle
      strength and running velocity were measured with field tests. RESULTS: As
      compared to placebo, the HICA supplementation increased significantly body weight
      (p < 0.005) and whole lean body mass (p < 0.05) while fat mass remained constant.
      The lean body mass of lower extremities increased by 400 g in HICA but decreased
      by 150 g in PLACEBO during the study. This difference between the groups was
      significant (p < 0.01). The HICA supplementation decreased the whole body DOMS
      symptoms in the 4(th )week of the treatment (p < 0.05) when compared to placebo.
      Muscle strength and running velocity did not differ between the groups.
      CONCLUSION: Already a 4-week HICA supplementation of 1.5 g a day leads to small
      increases in muscle mass during an intensive training period in soccer athletes.

PMID- 20051112
TI  - Serum levels of soluble Fas, soluble tumor necrosis factor-receptor II,
      interleukin-2 receptor and interleukin-8 as early predictors of hepatocellular
      carcinoma in Egyptian patients with hepatitis C virus genotype-4.
AB  - BACKGROUND: Liver disease progression from chronic hepatitis C virus (HCV)
      infection to hepatocellular carcinoma (HCC) is associated with an imbalance
      between T-helper 1 and T-helper 2 cytokines. Evaluation of cytokines as possible
      candidate biomarkers for prediction of HCC was performed using soluble Fas(sFas),
      soluble tumor necrosis factor receptor-II (sTNFR-II), interleukin-2 receptor (IL
      2R) and interleukin-8 (IL-8). RESULTS: The following patients were recruited: 79
      with HCV infection, 30 with HCC, 32 with chronic liver disease associated with
      elevated liver enzyme levels (with or without cirrhosis) in addition to 17 with
      chronic HCV with persistent normal alanine aminotransferase levels (PNALT). Nine
      normal persons negative either for HCV or for hepatitis B virus were included as
      a control group. All persons were tested for sFas, sTNFR-II, IL-2R and IL-8 in
      their serum by quantitative ELISA. HCC patients had higher levels of liver
      enzymes but lower log-HCV titer when compared to the other groups. HCC patients
      had also significantly higher levels of sFas, sTNFR-II and IL-2R and
      significantly lower levels of IL-8 when compared to the other groups. Exclusion
      of HCC among patients having PNALT could be predicted with 90 % sensitivity and
      70.6 % specificity when sTNFR-II is [greater than or equal to] 389 pg/ml or IL-8
      is < 290 pg/ml. CONCLUSIONS: Serum TNFR-II, IL-2Ralpha and IL-8, may be used as
      combined markers in HCV-infected cases for patients at high risk of developing
      HCC; further studies, however, are mandatory to check these findings before their
      application at the population level.

PMID- 20051113
TI  - Acute kidney injury in severe trauma assessed by RIFLE criteria: a common feature
      without implications on mortality?
AB  - BACKGROUND: Acute kidney injury (AKI) has been hard to assess due to the lack of
      standard definitions. Recently, the Risk, Injury, Failure, Loss and End-Stage
      Kidney (RIFLE) classification has been proposed to classify AKI in a number of
      clinical settings. This study aims to estimate the frequency and levels of
      severity of AKI and to study its association with patient mortality and length of
      stay (LOS) in a cohort of trauma patients needing intensive care. METHODS:
      Between August 2001 and September 2007, 436 trauma patients consecutively
      admitted to a general intensive care unit (ICU), were assessed using the RIFLE
      criteria. Demographic data, characteristics of injury, and severity of trauma
      variables were also collected. RESULTS: Half of all ICU trauma admissions had
      AKI, which corresponded to the group of patients with a significantly higher
      severity of trauma. Among patients with AKI, RIFLE class R (Risk) comprised 47%,
      while I (Injury) and F (Failure) were, 36% and 17%, respectively. None of these
      patients required renal replacement therapy. No significant differences were
      found among these three AKI classes in relation to patient's age, gender, type
      and mechanism of injury, severity of trauma or mortality. Nevertheless,
      increasing severity of acute renal injury was associated with a longer ICU stay.
      CONCLUSIONS: AKI is a common feature among trauma patients requiring intensive
      care. Although the development of AKI is associated with an increased LOS it does
      not appear to influence patient mortality.

PMID- 20051114
TI  - Schistosoma mansoni infection reduces the incidence of murine cerebral malaria.
AB  - BACKGROUND: Plasmodium and Schistosoma are two of the most common parasites in
      tropical areas. Deregulation of the immune response to Plasmodium falciparum,
      characterized by a Th1 response, leads to cerebral malaria (CM), while a Th2
      response accompanies chronic schistosomiasis. METHODS: The development of CM was
      examined in mice with concomitant Schistosoma mansoni and Plasmodium berghei ANKA
      infections. The effect of S. mansoni egg antigen injection on disease development
      and survival was also determined. Cytokine serum levels were estimated using
      ELISA. Statistical analysis was performed using t-test. RESULTS: The results
      demonstrate that concomitant S. mansoni and P. berghei ANKA infection leads to a
      reduction in CM. This effect is dependent on infection schedule and infecting
      cercariae number, and is correlated with a Th2 response. Schistosomal egg antigen
      injection delays the death of Plasmodium-infected mice, indicating immune
      involvement. CONCLUSIONS: This research supports previous claims of a protective
      effect of helminth infection on CM development. The presence of multiple
      parasitic infections in patients from endemic areas should therefore be carefully
      noted in clinical trials, and in the development of standard treatment protocols
      for malaria. Defined helminth antigens may be considered for alleviation of
      immunopathological symptoms.

PMID- 20051115
TI  - A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage
      disease type 0.
AB  - BACKGROUND: Glycogen storage disease type 0 is an autosomal recessive disease
      presenting in infancy or early childhood and characterized by ketotic
      hypoglycemia after prolonged fasting and postprandial hyperglycemia and
      hyperlactatemia. Sixteen different mutations have been identified to date in the
      gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen
      storage in the liver. CASE PRESENTATION: Biochemical evaluation as well as direct
      sequencing of exons and exon-intron boundary regions of the GYS2 gene were
      performed in a patient presenting fasting hypoglycemia and postprandial
      hyperglycemia and her parents. The patient was found to be compound heterozygous
      for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel
      frameshift mutation (966_967delGA/insC) which introduces a stop codon 21
      aminoacids downstream from the site of the mutation that presumably leads to loss
      of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of
      the parents after an oral glucose tolerance test were evaluated to investigate a
      possible impact of the carrier status on the metabolic profile. The mother, who
      presented a positive family history of type 2 diabetes, was classified as glucose
      intolerant and the father, who did not exhibit metabolic changes after the
      glucose overload, had an antecedent history of hypoglycemia after moderate
      alcohol ingestion. CONCLUSION: The current results expand the spectrum of known
      mutations in GYS2 and suggest that haploinsufficiency could explain metabolic
      abnormalities in heterozygous carriers in presence of predisposing conditions.

PMID- 20051116
TI  - Another look at Emergency Department HIV screening in practice: no need to revise
      expectations.
AB  - BACKGROUND: A recent study reported a lower than expected specificity and
      positive predictive value of the rapid oral HIV test in the setting of routine
      emergency department (ED) screening.   These results appeared inconsistent with
      the findings in another urban Emergency Department during the same time period.
      OBJECTIVE: To compare the specificity and positive predictive vale (PPV) of an
      oral rapid HIV test used in an ED screening program in Washington DC with that
      performed in the USHER clinical trial. DESIGN: Period cross-sectional analysis of
      rapid oral HIV testing conducted in an ongoing HIV screening program emergency
      department patients. SETTING: The George Washington University Emergency
      Department (Washington DC) from 7 February to 1 October 2007. PATIENTS: 1,560
      adults seen in the ED for non-HIV-related presenting complaints, who participated
      in the HIV screening program. INTERVENTION: Rapid HIV testing with the OraQuick
      ADVANCE Rapid HIV-1/2 Antibody Test (OraSure Technologies, Bethlehem,
      Pennsylvania). PATIENTS with reactive rapid test results were offered Western
      blot testing for confirmation. MEASUREMENTS: Specificity and positive predictive
      value for the program were determined.  Findings were compared to those found in
      the USHER trial. RESULTS: Of 1,560 patients screened for HIV, 13 [0.8%, 95% CI
      0.38% to 1.28%] had a reactive HIV screening test, and all were confirmed to be
      positive by Western Blot.  The specificity was 100% (95% CI 99.6%-100%).
      LIMITATION: Since non-reactive tests were not confirmed, the test sensitivity
      cannot be determined. CONCLUSION: Review of our data conflict with findings from
      the USHER study surrounding false positive OraQuick HIV screening. Our data
      suggest that rapid HIV screening protocols implemented in EDs outside of the
      clinical trial paradigm perform effectively without an excess of false positive
      results. Compared with other screening tests, HIV rapid screening should remain
      an essential component of ED practice.

PMID- 20051117
TI  - Expression of semaphorin 3A and its receptors in the human intervertebral disc:
      potential role in regulating neural ingrowth in the degenerate intervertebral
      disc.
AB  - INTRODUCTION: Intervertebral disc (IVD) degeneration is considered a major
      underlying factor in the pathogenesis of chronic low back pain. Although the
      healthy IVD is both avascular and aneural, during degeneration there is ingrowth
      of nociceptive nerve fibres and blood vessels into proximal regions of the IVD,
      which may contribute to the pain. The mechanisms underlying neural ingrowth are,
      however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance
      molecule with the ability to repel nerves seeking their synaptic target. This
      study aimed to identify whether members of the Class 3 semaphorins were expressed
      by chondrocyte-like cells of the IVD addressing the hypothesis that they may play
      a role in repelling axons surrounding the healthy disc, thus maintaining its
      aneural condition. METHODS: Human IVD samples were investigated using reverse
      transcription polymerase chain reaction (RT-PCR) to identify gene expression of
      sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A
      protein was also localised within sections of normal and degenerate human IVD and
      immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31
      to correlate semaphorin 3A expression with nerve and blood vessel ingrowth,
      respectively. RESULTS: Sema3A protein was expressed highly in the healthy disc,
      primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A
      expression decreased significantly in this region, although cell clusters within
      the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for
      sema3A receptors was also identified in healthy and degenerate tissues. CD31 and
      PGP9.5 were expressed most highly in degenerate tissues correlating with low
      expression of sema3A. CONCLUSIONS: This study is the first to establish the
      expression of semaphorins and their receptors in the human IVD with a decrease
      seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles,
      act as a barrier to neuronal ingrowth within the healthy disc.

PMID- 20051118
TI  - The Short Anxiety Screening Test in Greek: translation and validation.
AB  - BACKGROUND: The aim of the current study was to assess the reliability and
      validity of the Greek translation of the Short Anxiety Screening Test (SAST), for
      use in primary care settings. The scale consists of 10 items and is a brief
      clinician rating scale for the detection of anxiety disorder in older people,
      particularly, in the presence of depression. METHODS: The study was performed in
      two rural primary care settings in Crete. The sample consisted of 99 older (76 +/
      6.3 years old) people, who fulfilled the participating criteria. The translation
      and cultural adaptation of the questionnaire was performed according to
      international standards. Internal consistency using the Cronbach alpha
      coefficient and test-retest reliability using the intraclass correlation
      coefficient (ICC) was used to assess the reliability of the tool. An exploratory
      factor analysis using Varimax with Kaiser normalisation (rotation method) was
      used to examine the structure of the instrument, and for the correlation of the
      items interitem correlation matrix was applied and assessed with Cronbach alpha.
      RESULTS: Translation and backtranslation did not reveal any specific problems.
      The psychometric properties of the Greek version of the SAST scale in primary
      care were good. Internal consistency of the instrument was good, the Cronbach
      alpha was found to be 0.763 (P <0.001) and ICC (95% CI) for reproducibility was
      found to be 0.763 (0.686 to 0.827). Factor analysis revealed three factors with
      eigenvalues >1.0 accounting for 60% of variance, while the Cronbach alpha was
      >0.7 for every item. CONCLUSIONS: The Greek translation of the SAST questionnaire
      is comparable with that of the original version in terms of reliability, and can
      be used in primary healthcare research. Its use in clinical practice should be
      primarily as a screening tool only at this stage, with a follow-up consisting of
      a detailed interview with the patient, in order to confirm the diagnosis.

PMID- 20051119
TI  - Assessing a risk tailored intervention to prevent disabling low back pain-
      protocol of a cluster randomized controlled trial.
AB  - BACKGROUND: Although most patients with low back pain (LBP) recover within a few
      weeks a significant proportion has recurrent episodes or will develop chronic low
      back pain. Several mainly psychosocial risk factors for developing chronic LBP
      have been identified. However, effects of preventive interventions aiming at
      behavioural risk factors and unfavourable cognitions have yielded inconsistent
      results. Risk tailored interventions may provide a cost efficient and effective
      means to take systematic account of the individual risk factors but evidence is
      lacking. METHODS/DESIGN: This study will be a cluster-randomised controlled trial
      comparing screening and a subsequent risk tailored intervention for patients with
      low back pain to prevent chronic low back pain compared to treatment as usual in
      primary care. A total of 600 patients from 20 practices in each study arm will be
      recruited in Berlin and Goettingen. The intervention comprises the following
      elements: Patients will be assigned to one of four risk groups based on a
      screening questionnaire. Subsequently they receive an educational intervention
      including information and counselling tailored to the risk group. A
      telephone/email consulting service for back pain related problems are offered
      independent of risk group assignment. The primary outcomes will be functional
      capacity and sick leave. DISCUSSION: This trial will evaluate the effectiveness
      of screening for risk factors for chronic low back pain followed by a risk
      tailored intervention to prevent chronic low back pain. This trial will
      contribute new evidence regarding the flexible use of individual physical and
      psychosocial risk factors in general practice. TRIAL REGISTRATION: ISRCTN
      68205910.

PMID- 20051120
TI  - Therapeutic efficacy of Artemether/Lumefantrine (Coartem(R)) against Plasmodium
      falciparum in Kersa, South West Ethiopia.
AB  - BACKGROUND: Artemether/Lumefantrine (Coartem(R)) has been used as a first-line
      treatment for uncomplicated Plasmodium falciparum infection since 2004 in
      Ethiopia. In the present study the therapeutic efficacy of
      artemether/lumefantrine for the treatment of uncomplicated P. falciparum
      infection in Kersa, Jima zone, South-west Ethiopia, has been assessed. METHODS: A
      28 day therapeutic efficacy study was conducted between November 2007 and January
      2008, in accordance with the 2003 WHO guidelines. Outcomes were classified as
      early treatment failure (ETF), late clinical failure (LCF), late parasitological
      failure (LPF) and adequate clinical and parasitological response (ACPR). RESULTS:
      90 patients were enrolled and completed the 28 day follow-up period after
      treatment with artemether/lumefantrine. Cure rate was very high, 96.3%, with 95%
      CI of 0.897-0.992 (PCR uncorrected). Age-stratified data showed adequate clinical
      and parasitological response (ACPR) to be 100% for children under 5 and 97.4% and
      87.3% for  children aged 5-14, and adults, respectively. There was no early
      treatment failure (ETF) in all age groups. Fever was significantly cleared on day
      3 (P<0.05) and 98% of parasites where cleared on day 1 and almost all parasites
      were cleared  on day 3. 72.5% of gametocytes were cleared on day 1, the remaining
      27.5% of gametocytes were maintained up to day 3 and total clearance was observed
      on day 7. Hemoglobin concentration showed a slight increase with parasitic
      clearance (P>0.05). No major side effect was observed in the study except the
      occurrence of mouth ulcers in 7% of the patients. CONCLUSIONS: The current study
      proved the excellent therapeutic efficacy of artemether/lumefantrine in the study
      area and the value of using it. However, the proper dispensing and absorption of
      the drug need to be emphasized in order to utilize the drug for a longer period
      of time. This study recommends further study on the toxicity of the drug with
      particular emphasis on the development of oral ulcers in children.

PMID- 20051121
TI  - An evolutionary consequence of dosage compensation on Drosophila melanogaster
      female X-chromatin structure?
AB  - BACKGROUND: X chromosomes are subject to dosage compensation in Drosophila males.
      Dosage compensation requires cis sequence features of the X chromosome that are
      present in both sexes by definition and trans acting factors that target
      chromatin modifying machinery to the X specifically in males. The evolution of
      this system could result in neutral X chromatin changes that will be apparent in
      females. RESULTS: We find that the general chromatin structure of female X
      chromosomes is distinct from autosomes. Additionally, specific histone marks
      associated with dosage compensation and active chromatin marks on the male X
      chromosome are also enriched on the X chromosomes of females, albeit to a lesser
      degree. CONCLUSIONS: Our data indicate that X chromatin structure is
      fundamentally different from autosome structure in both sexes. We suggest that
      the differences between the X chromosomes and autosomes in females are a
      consequence of mechanisms that have evolved to ensure sufficient X chromosome
      expression in the soma of males.

PMID- 20051122
TI  - Decoding pooled RNAi screens by means of barcode tiling arrays.
AB  - BACKGROUND: RNAi screens via pooled short hairpin RNAs (shRNAs) have recently
      become a powerful tool for the identification of essential genes in mammalian
      cells. In the past years, several pooled large-scale shRNA screens have
      identified a variety of genes involved in cancer cell proliferation. All of those
      studies employed microarray analysis, utilizing either the shRNA's half hairpin
      sequence or an additional shRNA-associated 60 nt barcode sequence as a molecular
      tag. Here we describe a novel method to decode pooled RNAi screens, namely
      barcode tiling array analysis, and demonstrate how this approach can be used to
      precisely quantify the abundance of individual shRNAs from a pool. RESULTS: We
      synthesized DNA microarrays with six overlapping 25 nt long tiling probes
      complementary to each unique 60 nt molecular barcode sequence associated with
      every shRNA expression construct. By analyzing dilution series of expression
      constructs we show how our approach allows quantification of shRNA abundance from
      a pool and how it clearly outperforms the commonly used analysis via the shRNA's
      half hairpin sequences. We further demonstrate how barcode tiling arrays can be
      used to predict anti-proliferative effects of individual shRNAs from pooled
      negative selection screens. Out of a pool of 305 shRNAs, we identified 28
      candidate shRNAs to fully or partially impair the viability of the breast
      carcinoma cell line MDA-MB-231. Individual validation of a subset of eleven shRNA
      expression constructs with potential inhibitory, as well as non-inhibitory,
      effects on the cell line proliferation provides further evidence for the accuracy
      of the barcode tiling approach. CONCLUSIONS: In summary, we present an improved
      method for the rapid, quantitative and statistically robust analysis of pooled
      RNAi screens. Our experimental approach, coupled with commercially available
      lentiviral vector shRNA libraries, has the potential to greatly facilitate the
      discovery of putative targets for cancer therapy as well as sensitizers of drug
      toxicity.

PMID- 20051123
TI  - Impaired neurogenesis, learning and memory and low seizure threshold associated
      with loss of neural precursor cell survivin.
AB  - BACKGROUND: Survivin is a unique member of the inhibitor of apoptosis protein
      (IAP) family in that it exhibits antiapoptotic properties and also promotes the
      cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is
      highly expressed in neural precursor cells in the brain, yet its function there
      has not been elucidated. RESULTS: To examine the role of neural precursor cell
      survivin, we first showed that survivin is normally expressed in periventricular
      neurogenic regions in the embryo, becoming restricted postnatally to
      proliferating and migrating NPCs in the key neurogenic sites, the subventricular
      zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene
      inactivation strategy to delete the survivin gene prenatally in those neurogenic
      regions. Lack of embryonic NPC survivin results in viable, fertile mice
      (SurvivinCamcre) with reduced numbers of SVZ NPCs, absent rostral migratory
      stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as
      intracerebroventricular gene delivery of survivin during embryonic development
      increases olfactory bulb neurogenesis, detected postnatally. SurvivinCamcre
      brains have fewer cortical inhibitory interneurons, contributing to enhanced
      sensitivity to seizures, and profound deficits in memory and learning.
      CONCLUSIONS: The findings highlight the critical role that survivin plays during
      neural development, deficiencies of which dramatically impact on postnatal neural
      function.

PMID- 20051124
TI  - Bio-psychosocial determinants of time lost from work following non life
      threatening acute orthopaedic trauma.
AB  - BACKGROUND: To determine factors predicting the duration of time away from work
      following acute orthopaedic non life threatening trauma METHODS: Prospective
      cohort study conducted at four hospitals in Victoria, Australia. The cohort
      comprised 168 patients aged 18-64 years who were working prior to the injury and
      sustained a range of acute unintentional orthopaedic injuries resulting in
      hospitalization. Baseline data was obtained by survey and medical record review.
      Multivariate Cox proportional hazards regression analysis was used to examine the
      association between potential predictors and the duration of time away from work
      during the six month study. The study achieved 89% follow-up. RESULTS: Of the 168
      participants recruited to the study, 68% returned to work during the six month
      study. Multivariate Cox proportional hazards regression analysis identified that
      blue collar work, negative pain attitudes with respect to work, high initial pain
      intensity, injury severity, older age, initial need for surgery, the presence of
      co-morbid health conditions at study entry and an orthopaedic injury to more than
      one region were associated with extended duration away from work following the
      injury. Participants in receipt of compensation who reported high social
      functioning at two weeks were 2.58 times more likely to have returned to work
      than similar participants reporting low social functioning. When only those who
      had returned to work were considered, the participant reported reason for return
      to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41
      (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to"
      did not achieve significance. CONCLUSIONS: Many injury-related and psycho social
      factors affect the duration of time away from work following orthopaedic injury.
      Some of these are potentially modifiable and may be amenable to intervention.
      Further consideration of the reasons provided by participants for returning to
      work may provide important opportunities for social marketing approaches designed
      to alleviate the financial and social burden associated with work disability.

PMID- 20051125
TI  - Conceptual and practical challenges for implementing the communities of practice
      model on a national scale--a Canadian cancer control initiative.
AB  - BACKGROUND: Cancer program delivery, like the rest of health care in Canada,
      faces two ongoing challenges: to coordinate a pan-Canadian approach across
      complex provincial jurisdictions, and to facilitate the rapid translation of
      knowledge into clinical practice. Communities of practice, or CoPs, which have
      been described by Etienne Wenger as a collaborative learning platform, represent
      a promising solution to these challenges because they rely on bottom-up rather
      than top-down social structures for integrating knowledge and practice across
      regions and agencies. The communities of practice model has been realized in the
      corporate (e.g., Royal Dutch Shell, Xerox, IBM, etc) and development (e.g., World
      Bank) sectors, but its application to health care is relatively new. The Canadian
      Partnership Against Cancer (CPAC) is exploring the potential of Wenger's concept
      in the Canadian health care context. This paper provides an in-depth analysis of
      Wenger's concept with a focus on its applicability to the health care sector.
      DISCUSSION: Empirical studies and social science theory are used to examine the
      utility of Wenger's concept. Its value lies in emphasizing learning from peers
      and through practice in settings where innovation is valued. Yet the communities
      of practice concept lacks conceptual clarity because Wenger defines it so broadly
      and sidelines issues of decision making within CoPs. We consider the implications
      of his broad definition to establishing an informed nomenclature around this
      specific type of collaborative group. The CoP Project under CPAC and communities
      of practice in Canadian health care are discussed. SUMMARY: The use of
      communities of practice in Canadian health care has been shown in some instances
      to facilitate quality improvements, encourage buy in among participants, and
      generate high levels of satisfaction with clinical leadership and knowledge
      translation among participating physicians. Despite these individual success
      stories, more information is required on how group decisions are made and applied
      to the practice world in order to leverage the potential of Wenger's concept more
      fully, and advance the science of knowledge translation within an accountability
      framework.

PMID- 20051126
TI  - TreeGraph 2: combining and visualizing evidence from different phylogenetic
      analyses.
AB  - BACKGROUND: Today it is common to apply multiple potentially conflicting data
      sources to a given phylogenetic problem. At the same time, several different
      inference techniques are routinely employed instead of relying on just one. In
      view of both trends it is becoming increasingly important to be able to
      efficiently compare different sets of statistical values supporting (or
      conflicting with) the nodes of a given tree topology, and merging this into a
      meaningful representation. A tree editor supporting this should also allow for
      flexible editing operations and be able to produce ready-to-publish figures.
      RESULTS: We developed TreeGraph 2, a GUI-based graphical editor for phylogenetic
      trees (available from http://treegraph.bioinfweb.info). It allows automatically
      combining information from different phylogenetic analyses of a given dataset (or
      from different subsets of the dataset), and helps to identify and graphically
      present incongruences. The program features versatile editing and formatting
      options, such as automatically setting line widths or colors according to the
      value of any of the unlimited number of variables that can be assigned to each
      node or branch. These node/branch data can be imported from spread sheets or
      other trees, be calculated from each other by specified mathematical expressions,
      filtered, copied from and to other internal variables, be kept invisible or set
      visible and then be freely formatted (individually or across the whole tree).
      Beyond typical editing operations such as tree rerooting and ladderizing or
      moving and collapsing of nodes, whole clades can be copied from other files and
      be inserted (along with all node/branch data and legends), but can also be
      manually added and, thus, whole trees can quickly be manually constructed de
      novo. TreeGraph 2 outputs various graphic formats such as SVG, PDF, or PNG,
      useful for tree figures in both publications and presentations. CONCLUSION:
      TreeGraph 2 is a user-friendly, fully documented application to produce ready-to
      publish trees. It can display any number of annotations in several ways, and
      permits easily importing and combining them. Additionally, a great number of
      editing- and formatting-operations is available.

PMID- 20051127
TI  - A novel approach to simulate gene-environment interactions in complex diseases.
AB  - BACKGROUND: Complex diseases are multifactorial traits caused by both genetic and
      environmental factors. They represent the major part of human diseases and
      include those with largest prevalence and mortality (cancer, heart disease,
      obesity, etc.). Despite a large amount of information that has been collected
      about both genetic and environmental risk factors, there are few examples of
      studies on their interactions in epidemiological literature. One reason can be
      the incomplete knowledge of the power of statistical methods designed to search
      for risk factors and their interactions in these data sets. An improvement in
      this direction would lead to a better understanding and description of gene
      environment interactions. To this aim, a possible strategy is to challenge the
      different statistical methods against data sets where the underlying phenomenon
      is completely known and fully controllable, for example simulated ones. RESULTS:
      We present a mathematical approach that models gene-environment interactions. By
      this method it is possible to generate simulated populations having gene
      environment interactions of any form, involving any number of genetic and
      environmental factors and also allowing non-linear interactions as epistasis. In
      particular, we implemented a simple version of this model in a Gene-Environment
      iNteraction Simulator (GENS), a tool designed to simulate case-control data sets
      where a one gene-one environment interaction influences the disease risk. The
      main aim has been to allow the input of population characteristics by using
      standard epidemiological measures and to implement constraints to make the
      simulator behaviour biologically meaningful. CONCLUSIONS: By the multi-logistic
      model implemented in GENS it is possible to simulate case-control samples of
      complex disease where gene-environment interactions influence the disease risk.
      The user has full control of the main characteristics of the simulated population
      and a Monte Carlo process allows random variability. A knowledge-based approach
      reduces the complexity of the mathematical model by using reasonable biological
      constraints and makes the simulation more understandable in biological terms.
      Simulated data sets can be used for the assessment of novel statistical methods
      or for the evaluation of the statistical power when designing a study.

PMID- 20051128
TI  - Treatment outcome of thalidomide based regimens in newly diagnosed and
      relapsed/refractory non-transplant multiple myeloma patients: a single center
      experience from Thailand.
AB  - BACKGROUND: Thalidomide based regimen is an effective and well tolerated therapy
      in multiple myeloma (MM) patients, however, there were a small number of studies
      written about the results of thalidomide therapy in non-transplant MM patients.
      We therefore conducted a retrospective study of 42 consecutive patients with
      newly diagnosed and relapsed/refractory MM treated with thalidomide- based
      induction regimens followed by thalidomide maintenance therapy. RESULTS:
      Induction regimens with thalidomide and dexamethasone, and the oral combination
      of melphalan, prednisolone and thalidomide were administrated in 22 and 16
      patients, respectively. The remaining 4 patients received other thalidomide-
      containing regimens. Twenty-nine patients received thalidomide as a salvage
      regimen. Twenty-three out of 26 patients achieving complete remission (CR) and
      very good partial remission (VGPR) received thalidomide maintenance. Of the 41
      evaluable patients, median time of treatment was 21 months (3- 45 months), ORR
      was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS
      and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was
      42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving
      thalidomide maintenance therapy were 67 and 80%, respectively. CONCLUSIONS:
      Prolonged thalidomide therapy enhanced survival rate and less frequently
      developed serious toxicity in non-transplant multiple myeloma patients.

PMID- 20051129
TI  - Differential expression of Toll-like receptors on human alveolar macrophages and
      autologous peripheral monocytes.
AB  - BACKGROUND: Toll-like receptors (TLRs) are critical components in the regulation
      of pulmonary immune responses and the recognition of respiratory pathogens such
      as Mycobacterium Tuberculosis (M.tb). Through examination of human alveolar
      macrophages this study attempts to better define the expression profiles of TLR2,
      TLR4 and TLR9 in the human lung compartment which are as yet still poorly
      defined. METHODS: Sixteen healthy subjects underwent venipuncture, and eleven
      subjects underwent additional bronchoalveolar lavage to obtain peripheral blood
      mononuclear and bronchoalveolar cells, respectively. Surface and intracellular
      expression of TLRs was assessed by fluorescence-activated cell sorting and qRT
      PCR. Cells were stimulated with TLR-specific ligands and cytokine production
      assessed by ELISA and cytokine bead array. RESULTS: Surface expression of TLR2
      was significantly lower on alveolar macrophages than on blood monocytes (1.2 +/-
      0.4% vs. 57 +/- 11.1%, relative mean fluorescence intensity [rMFI]: 0.9 +/- 0.1
      vs. 3.2 +/- 0.1, p < 0.05). The proportion of TLR4 and TLR9-expressing cells and
      the rMFIs of TLR4 were comparable between alveolar macrophages and monocytes. The
      surface expression of TLR9 however, was higher on alveolar macrophages than on
      monocytes (rMFI, 218.4 +/- 187.3 vs. 4.4 +/- 1.4, p < 0.05) while the
      intracellular expression of the receptor and the proportion of TLR9 positive
      cells were similar in both cell types. TLR2, TLR4 and TLR9 mRNA expression was
      lower in bronchoalveolar cells than in monocytes.Pam3Cys, LPS, and M.tb DNA
      upregulated TLR2, TLR4 and TLR9 mRNA in both, bronchoalveolar cells and
      monocytes. Corresponding with the reduced surface and mRNA expression of TLR2,
      Pam3Cys induced lower production of TNF-alpha, IL-1beta and IL-6 in
      bronchoalveolar cells than in monocytes. Despite comparable expression of TLR4 on
      both cell types, LPS induced higher levels of IL-10 in monocytes than in alveolar
      macrophages. M.tb DNA, the ligand for TLR9, induced similar levels of cytokines
      in both cell types. CONCLUSION: The TLR expression profile of autologous human
      alveolar macrophages and monocytes is not identical, therefore perhaps
      contributing to compartmentalized immune responses in the lungs and systemically.
      These dissimilarities may have important implications for the design and efficacy
      evaluation of vaccines with TLR-stimulating adjuvants that target the respiratory
      tract.

PMID- 20051130
TI  - Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods.
AB  - OBJECTIVE: To present the design, methods, and rationale of the Child/Adolescent
      Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi
      site, randomized placebo-controlled trial that examined the relative efficacy of
      cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB)
      against pill placebo (PBO) for the treatment of separation anxiety disorder
      (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and
      adolescents. METHODS: Following a brief review of the acute outcomes of the CAMS
      trial, as well as the psychosocial and pharmacologic treatment literature for
      pediatric anxiety disorders, the design and methods of the CAMS trial are
      described. RESULTS: CAMS was a six-year, six-site, randomized controlled trial.
      Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years)
      with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of
      four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety
      symptoms, safety, and functional outcomes, as well as putative mediators and
      moderators of treatment response were completed in a multi-measure, multi
      informant fashion. Manual-based therapies, trained clinicians and independent
      evaluators were used to ensure treatment and assessment fidelity. A multi-layered
      administrative structure with representation from all sites facilitated cross
      site coordination of the entire trial, study protocols and quality assurance.
      CONCLUSIONS: CAMS offers a model for clinical trials methods applicable to
      psychosocial and psychopharmacological comparative treatment trials by using
      state-of-the-art methods and rigorous cross-site quality controls. CAMS also
      provided a large-scale examination of the relative and combined efficacy and
      safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI)
      treatments to date for the most commonly occurring pediatric anxiety disorders.
      Primary and secondary results of CAMS will hold important implications for
      informing practice-relevant decisions regarding the initial treatment of youth
      with anxiety disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT00052078.

PMID- 20051131
TI  - A comparison of the clinical effectiveness and costs of mental health nurse
      supplementary prescribing and independent medical prescribing: a post-test
      control group study.
AB  - BACKGROUND: Supplementary prescribing for mental health nurses was first
      introduced in the UK in 2003. Since then, a number of studies have reported
      stakeholders' perceptions of the success of the initiative. However, there has
      been little experimental research conducted into its effectiveness. This paper
      reports findings from the first known study to compare the cost and clinical
      impact of mental health nurse supplementary prescribing to independent medical
      prescribing. METHODS: A post-test control group experimental design was used to
      compare the treatment costs, clinical outcomes and satisfaction of patients in
      receipt of mental health nurse supplementary prescribing with a matched group of
      patients in receipt of independent prescribing from consultant psychiatrists. The
      sample comprised 45 patients in receipt of mental health nurse supplementary
      prescribing for a minimum of six months and a matched group (by age, gender,
      diagnosis, and chronicity) of patients prescribed for by psychiatrists. RESULTS:
      There were no significant differences between patients in the nurse supplementary
      prescribers' group and the independent prescribers' group in terms of medication
      adherence, health status, side effects, and satisfaction with overall care. Total
      costs per patient for service use were 803 pounds higher for the nurse
      prescribers' group but this difference was not significant (95% confidence
      interval--1341 pounds to 3020 pounds). CONCLUSIONS: No significant differences
      were found between the health and social outcomes of patients in the mental
      health nurse supplementary prescribers' group, and those prescribed for by the
      independent medical prescribers. The cost appraisal also showed that there was no
      significant difference in the costs of the two types of prescribing, although the
      pattern of resources used differed between patients in the two prescriber groups.
      The results suggest that mental health nurse supplementary prescribers can
      deliver similar health benefits to patients as consultant psychiatrists without
      any significant difference in patients' service utilisation costs.

PMID- 20051132
TI  - A simple algebraic cancer equation: calculating how cancers may arise with normal
      mutation rates.
AB  - BACKGROUND: The purpose of this article is to present a relatively easy to
      understand cancer model where transformation occurs when the first cell, among
      many at risk within a colon, accumulates a set of driver mutations. The analysis
      of this model yields a simple algebraic equation, which takes as inputs the
      number of stem cells, mutation and division rates, and the number of driver
      mutations, and makes predictions about cancer epidemiology. METHODS: The equation
      [p = 1 - (1 - (1 - (1 - u)d)k)Nm ] calculates the probability of cancer (p) and
      contains five parameters: the number of divisions (d), the number of stem cells
      (N x m), the number of critical rate-limiting pathway driver mutations (k), and
      the mutation rate (u). In this model progression to cancer "starts" at conception
      and mutations accumulate with cell division. Transformation occurs when a
      critical number of rate-limiting pathway mutations first accumulates within a
      single stem cell. RESULTS: When applied to several colorectal cancer data sets,
      parameter values consistent with crypt stem cell biology and normal mutation
      rates were able to match the increase in cancer with aging, and the mutation
      frequencies found in cancer genomes. The equation can help explain how cancer
      risks may vary with age, height, germline mutations, and aspirin use. APC
      mutations may shorten pathways to cancer by effectively increasing the numbers of
      stem cells at risk. CONCLUSIONS: The equation illustrates that age-related
      increases in cancer frequencies may result from relatively normal division and
      mutation rates. Although this equation does not encompass all of the known
      complexity of cancer, it may be useful, especially in a teaching setting, to help
      illustrate relationships between small and large cancer features.

PMID- 20051133
TI  - Clinical profile of parkinsonism and Parkinson's disease in Lagos, Southwestern
      Nigeria.
AB  - BACKGROUND: Current data on the pattern of parkinsonism and Parkinson's disease
      in Nigerians are sparse.This database was designed to document the clinical
      profile of PD in Nigerians, and compare this to prior observations. METHODS: A
      database of patients presenting to the Neurology out-patients clinic of the Lagos
      University Teaching Hospital was established in October 1996. Demographic and
      clinical data at presentation (disease stage using Hoehn and Yahr scale; 'off'
      state severity on the Unified Parkinson's disease Rating Scale) were documented
      for patients diagnosed with parkinsonism between October 1996 and December 2006.
      Cases were classified as Parkinson's disease or secondary parkinsonism (in the
      presence of criteria suggestive of a secondary aetiology). RESULTS: The hospital
      frequency of parkinsonism (over a 2-year period, and relative to other neurologic
      disorders) was 1.47% (i.e. 20/1360). Of the 124 patients with parkinsonism, 98
      (79.0%) had PD, while 26 (21.0%) had secondary parkinsonism. Mean age (SD) at
      onset of PD (61.5 (10.0) years) was slightly higher than for secondary
      parkinsonism (57.5 (14.0) years) (P = 0.10). There was a male preponderance in PD
      (3.3 to 1) and secondary parkinsonism (2.7 to 1), while a positive family history
      of parkinsonism was present in only 1.02% (1/98) of PD. There was a modestly
      significant difference in age at onset (SD) of PD in men (60.3 (10.4)) compared
      to women (65.2 (7.9)) (T = 2.08; P = 0.04). The frequency of young onset PD (< or
      = 50 years) was 16.3% (16/98). The mean time interval from onset of motor
      symptoms to diagnosis of PD was 24.6 +/- 26.1 months with majority presenting at
      a median 12 months from onset. On the H&Y scale, severity of PD at presentation
      was a median 2.0 (range 1 to 4). PD disease subtype was tremor-dominant in 31
      (31.6%), mixed 54 (55.1%) and akinetic-rigid 14 (14.3%). Hypertension was present
      as a co-morbidity in 20 (20.4%), and diabetes in 6 (6.12%). CONCLUSIONS: The
      clinical profile of PD in Nigerians is similar to that in other populations, but
      is characterized by delayed presentation as has been reported in other developing
      countries. Young-onset disease occurs but may be less commonly encountered, and
      frequency of a positive family history is lower than in western populations.

PMID- 20051134
TI  - Residual gammaH2AX foci as an indication of lethal DNA lesions.
AB  - BACKGROUND: Evidence suggests that tumor cells exposed to some DNA damaging
      agents are more likely to die if they retain microscopically visible gammaH2AX
      foci that are known to mark sites of double-strand breaks. This appears to be
      true even after exposure to the alkylating agent MNNG that does not cause direct
      double-strand breaks but does produce gammaH2AX foci when damaged DNA undergoes
      replication. METHODS: To examine this predictive ability further, SiHa human
      cervical carcinoma cells were exposed to 8 DNA damaging drugs (camptothecin,
      cisplatin, doxorubicin, etoposide, hydrogen peroxide, MNNG, temozolomide, and
      tirapazamine) and the fraction of cells that retained gammaH2AX foci 24 hours
      after a 30 or 60 min treatment was compared with the fraction of cells that lost
      clonogenicity. To determine if cells with residual repair foci are the cells that
      die, SiHa cervical cancer cells were stably transfected with a RAD51-GFP
      construct and live cell analysis was used to follow the fate of irradiated cells
      with RAD51-GFP foci. RESULTS: For all drugs regardless of their mechanism of
      interaction with DNA, close to a 1:1 correlation was observed between clonogenic
      surviving fraction and the fraction of cells that retained gammaH2AX foci 24
      hours after treatment. Initial studies established that the fraction of cells
      that retained RAD51 foci after irradiation was similar to the fraction of cells
      that retained gammaH2AX foci and subsequently lost clonogenicity. Tracking
      individual irradiated live cells confirmed that SiHa cells with RAD51-GFP foci 24
      hours after irradiation were more likely to die. CONCLUSION: Retention of DNA
      damage-induced gammaH2AX foci appears to be indicative of lethal DNA damage so
      that it may be possible to predict tumor cell killing by a wide variety of DNA
      damaging agents simply by scoring the fraction of cells that retain gammaH2AX
      foci.

PMID- 20051135
TI  - Improved adherence with once-daily versus twice-daily dosing of mometasone
      furoate administered via a dry powder inhaler: a randomized open-label study.
AB  - BACKGROUND: Poor adherence with prescribed asthma medication is a major barrier
      to positive treatment outcomes. This study was designed to determine the effect
      of a once-daily administration of mometasone furoate administered via a dry
      powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily
      administration. METHODS: This was a 12-week open-label study designed to mimic an
      actual clinical setting in patients >or=12 years old with mild-to-moderate
      persistent asthma. Patients were randomized to receive MF-DPI 400 microg once
      daily in the evening or MF-DPI 200 microg twice-daily. Adherence was assessed
      primarily using the number of actual administered doses reported from the device
      counter divided by the number of scheduled doses. Self-reports were also used to
      determine adherence. Health-related quality of life, healthcare resource
      utilization, and days missed from work or school were also reported. RESULTS:
      1233 patients were randomized. The mean adherence rates, as measured by the
      automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400
      microg once-daily in the evening (93.3%) than with MF-DPI 200 microg twice-daily
      (89.5%). Mean adherence rates based on self-reports were also significantly
      better (P < 0.001) with MF-DPI 400 microg QD PM (97.2%) than with MF-DPI 200
      microg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17
      years old). Health-related quality of life improved by 20% in patients using MF
      DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily.
      Very few (<8%) patients missed work/school. CONCLUSION: Mean adherence rates were
      greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing
      regimen.This trial was completed prior to the ISMJE requirements for trial
      registration.

PMID- 20051136
TI  - Impact of clinical urgency, physician supply and procedural capacity on regional
      variations in wait times for coronary angiography.
AB  - BACKGROUND: Despite universal health care, there continues to be regional access
      disparities to coronary angiography in Canada. Our objective was to evaluate the
      extent to which demand-side factors such as clinical urgency/need, and supply
      side factors, as reflected by differences in physician and procedural supply
      account for these inequalities. METHODS: Our cohort consisted of 74,254
      consecutive patients referred for coronary angiography in Ontario, Canada between
      April 1st 2005 and March 31st 2006, divided into three urgency strata based on a
      clinical urgency scale. Cox-proportional hazard models were developed, adjusting
      for age, gender, socioeconomic status (SES), region, and urgency score, with
      greater hazard ratios (HR) indicating shorter wait times. To evaluate mediators
      of any residual wait-time differences, we examined the influence of the regional
      supply of cath lab facilities, invasive cardiologists and general practitioners
      (GP). RESULTS: We found that the urgency score was a significant predictor of
      wait time in all three strata (urgent patients: HR 1.61 for each unit increase in
      patient urgency (95% Confidence interval (CI) 1.55-1.67); semi-urgent patients:
      HR 1.55 (95% CI 1.44-1.68); elective patients: HR 1.13 (95% CI 1.08-1.18)). After
      accounting for clinical need/urgency, regional wait time differences persisted;
      these were most consistently associated with variation in cath lab supply. The
      impact of invasive cardiologist supply was restricted to urgent patients while
      that of GP supply was confined to semi-urgent and elective patients. CONCLUSION:
      We found that there remained significant regional disparities in access to
      coronary angiography after accounting for clinical need. These disparities are
      partially explained by variations in supply of both procedural capacity and
      physician services, most notably in elective and semi-urgent patients.

PMID- 20051137
TI  - Honoring Leslie A. Geddes - farewell ...
AB  - Honor thy father and thy mother, say the Holy Scriptures1, for they at least gave
      thee this biological life, but honor thy teachers, too, for they gave thee
      knowledge and example.Leslie Alexander Geddes took off on a long, long trip,
      Sunday October 25, 2009, leaving his body for medical and research use. The
      departing station was West Lafayette, Indiana, where he set foot in 1974, at
      Purdue University, stamping there a unique deep imprint, similar and probably
      more profound than the one left at Baylor College of Medicine (BCM), Houston,
      Texas, in the period 1955-1974. Memories came back as a flood the minute after a
      message broke the news to me: When I first met him visiting the Department of
      Physiology at BCM back in 1962, my first Classical Physiology with Modern
      Instrumentation Summer Course ... The versatile Physiograph was the main
      equipment, an electronic-mechanical three or four channel recorder that could
      pick up a variety of physiological variables. Les and his collaborators had
      introduced also the impedance pneumograph, which was a simplified version of
      previous developments made by others. It became a ubiquitous unit that trod many
      roads in the hands of eager and curious students. Ventricular fibrillation and
      especially its counterpart, defibrillation, stand out as subjects occupying his
      concern along the years. Many were the students recruited to such effort and long
      is the list of papers on the subject. Physiological signals attracted
      considerable part of his activities because one of his perennial mottos was
      measurement is essential in physiology. He has written thirteen books and over
      eight hundred scientific papers, receiving also several prizes and distinctions.
      Not only his interests stayed within the academic environment but an industrial
      hue was manifested in over 20 USA patents, all applied to medical use. History of
      science and technology was another area in which, often with Hebbel Hoff, he
      uncovered astounding and delightful information. It is beyond my capability to
      review everything Les did, least of all what he did during the long span at
      Purdue.

PMID- 20051138
TI  - Non- medical prescribing in Australasia and the UK: the case of podiatry.
AB  - BACKGROUND: The last decade has witnessed a rapid transformation in the role
      boundaries of the allied health professions, enabled through the creation of new
      roles and the expansion of existing, traditional roles. A strategy of health care
      'modernisation' has encompassed calls for the redrawing of professional
      boundaries and identities, linked with demands for greater workforce flexibility.
      Several tasks and roles previously within the exclusive domain of medicine have
      been delegated to, or assumed by, allied health professionals, as the workforce
      is reshaped to meet the challenges posed by changing demographic, social and
      political contexts. The prescribing of medicines by non-medically qualified
      healthcare professionals, and in particular the podiatry profession, reflects
      these changes. METHODS: Using a range of key primary documentary sources derived
      from published material in the public domain and unpublished material in private
      possession, this paper traces the development of contemporary UK and Australasian
      podiatric prescribing, access, supply and administration of medicines.
      Documentary sources include material from legislative, health policy, regulatory
      and professional bodies (including both State and Federal sources in Australia).
      RESULTS: Tracing a chronological, comparative, socio-historical account of the
      emergence and development of 'prescribing' in podiatry in both Australasia and
      the UK enables an analysis of the impact of health policy reforms on the use of,
      and access to, medicines by podiatrists. The advent of neo-liberal healthcare
      policies, coupled with demands for workforce flexibility and role transfer within
      a climate of demographic, economic and social change has enabled allied health
      professionals to undertake an expanding number of tasks involving the sale,
      supply, administration and prescription of medicines. CONCLUSION: As a challenge
      to medical dominance, these changes, although driven by wider healthcare policy,
      have met with resistance. As anticipated in the theory of medical dominance,
      inter-professional jurisdictional disputes centred on the right to access,
      administer, supply and prescribe medicines act as obstacles to workforce change.
      Nevertheless, the broader policy agenda continues to ensure workforce redesign in
      which podiatry has assumed wider roles and responsibilities in prescribing.

PMID- 20051139
TI  - Detecting positive selection from genome scans of linkage disequilibrium.
AB  - BACKGROUND: Though a variety of linkage disequilibrium tests have recently been
      introduced to measure the signal of recent positive selection, the statistical
      properties of the various methods have not been directly compared. While most
      applications of these tests have suggested that positive selection has played an
      important role in recent human history, the results of these tests have varied
      dramatically. RESULTS: Here, we evaluate the performance of three statistics
      designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To
      analyze the properties of these tests, we introduce a new computational method
      that can model complex population histories with migration and changing
      population sizes to simulate gene trees influenced by recent positive selection.
      We demonstrate that iHS performs substantially better than the other two
      statistics, with power of up to 0.74 at the 0.01 level for the variation best
      suited for full genome scans and a power of over 0.8 at the 0.01 level for the
      variation best suited for candidate gene tests. The performance of the iHS
      statistic was robust to complex demographic histories and variable recombination
      rates. Genome scans involving the other two statistics suffer from low power and
      high false positive rates, with false discovery rates of up to 0.96 for ALnLH.
      The difference in performance between iHS and ALnLH, did not result from the
      properties of the statistics, but instead from the different methods for
      mitigating the multiple comparison problem inherent in full genome scans.
      CONCLUSIONS: We introduce a new method for simulating genealogies influenced by
      positive selection with complex demographic scenarios. In a power analysis based
      on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective
      sweeps. We also show that the single-site iHS statistic is more powerful in a
      candidate gene test than the multi-site statistic, but that the multi-site
      statistic maintains a low false discovery rate with only a minor loss of power
      when applied to a scan of the entire genome. Our results highlight the need for
      careful consideration of multiple comparison problems when evaluating and
      interpreting the results of full genome scans for positive selection.

PMID- 20051140
TI  - ANMM4CBR: a case-based reasoning method for gene expression data classification.
AB  - BACKGROUND: Accurate classification of microarray data is critical for successful
      clinical diagnosis and treatment. The "curse of dimensionality" problem and noise
      in the data, however, undermines the performance of many algorithms. METHOD: In
      order to obtain a robust classifier, a novel Additive Nonparametric Margin
      Maximum for Case-Based Reasoning (ANMM4CBR) method is proposed in this article.
      ANMM4CBR employs a case-based reasoning (CBR) method for classification. CBR is a
      suitable paradigm for microarray analysis, where the rules that define the domain
      knowledge are difficult to obtain because usually only a small number of training
      samples are available. Moreover, in order to select the most informative genes,
      we propose to perform feature selection via additively optimizing a nonparametric
      margin maximum criterion, which is defined based on gene pre-selection and sample
      clustering. Our feature selection method is very robust to noise in the data.
      RESULTS: The effectiveness of our method is demonstrated on both simulated and
      real data sets. We show that the ANMM4CBR method performs better than some state
      of-the-art methods such as support vector machine (SVM) and k nearest neighbor
      (kNN), especially when the data contains a high level of noise. AVAILABILITY: The
      source code is attached as an additional file of this paper.

PMID- 20051141
TI  - Cellular receptor binding and entry of human papillomavirus.
AB  - Human papillomaviruses (HPVs), recognized as the etiological agents for the skin,
      plantar, genital, and laryngopharyngeal wart, have been previously in numerous
      studies demonstrated to present a close link between HPV infection and certain
      human cancers, some putative candidates of HPV cell receptor and possible
      pathways of cell entry proposed. This review was to highlight the investigations
      and remaining questions regarding the binding and entry process.

PMID- 20051142
TI  - Tocotrienols are good adjuvants for developing cancer vaccines.
AB  - BACKGROUND: Dendritic cells (DCs) have the potential for cancer immunotherapy due
      to their ability to process and present antigens to T-cells and also in
      stimulating immune responses. However, DC-based vaccines have only exhibited
      minimal effectiveness against established tumours in mice and humans. The use of
      appropriate adjuvant enhances the efficacy of DC based cancer vaccines in
      treating tumours. METHODS: In this study we have used tocotrienol-rich fraction
      (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness
      of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week
      old female BALB/c mice were injected subcutaneously with DC and supplemented with
      oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL).
      Experimental mice were also injected with DC pulsed with tumour lysate and
      supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which
      were supplemented daily with carrier oil (control) and with TRF (TRF). After
      three times vaccination, mice were inoculated with 4T1 cells in the mammary
      breast pad to induce tumour. RESULTS: Our study showed that TRF in combination
      with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously
      significantly inhibited the growth of 4T1 mammary tumour cells as compared to
      control group. Analysis of cytokines production from murine splenocytes showed
      significant increased productions of IFN-gamma and IL-12 in experimental mice
      (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected
      with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher
      numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in
      the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. CONCLUSION:
      Our study show that TRF has the potential to be an adjuvant to augment DC based
      immunotherapy.

PMID- 20051143
TI  - Attraction of Anopheles gambiae to odour baits augmented with heat and moisture.
AB  - BACKGROUND: The search for a standard human surrogate in the form of a synthetic
      mosquito attractant has been the goal of many laboratories around the world.
      Besides alleviating the occupational risk subjected to volunteers participating
      in vector surveillance and control, discovery of potent attractants underpins the
      development and deployment of mass trapping devices for controlling mosquito
      borne diseases. METHODS: A dual-port olfactometer was used to assess behavioural
      responses of female Anopheles gambiae mosquitoes towards synthetic versus natural
      (whole human emanations and worn socks) attractants. The synthetic attractants
      included a standard blend consisting of ammonia, carbon dioxide and water; and
      Ifakara blend 1 (IB1) consisting of various aliphatic carboxylic acids. Natural
      attractants were obtained from two males known to be less and highly attractive
      (LA and HA, respectively) to the mosquitoes. Mosquito responses to the
      volunteers' worn socks were also investigated. The effect of heat (25-27 degrees
      C) and moisture (75-85%) on the mosquito behavioural responses was determined.
      RESULTS: A significantly higher proportion of mosquitoes was attracted to each
      volunteer when compared to the standard blend. Whereas the proportion of
      mosquitoes attracted to person LA versus IB1 (49% versus 51%, respectively; P =
      0.417) or his worn socks did not differ (61% versus 39%, respectively; P =
      0.163), far more mosquitoes were attracted to person HA relative to IB1 (96%
      versus 4%; P = 0.001) or his worn socks (91% versus 9%; P = 0.001). Person HA
      attracted a significantly higher proportion of mosquitoes than his worn socks,
      the standard blend and IB1 when these were augmented with heat, moisture or both
      (P = 0.001). Similar results were obtained with person LA except that the
      proportion of mosquitoes attracted to him versus his worn sock augmented with
      heat (P = 0.65) or IB1 augmented with heat and moisture (P = 0.416) did not
      differ significantly. CONCLUSIONS: These findings indicate that olfactory cues
      are key mediators of the mosquito host-seeking process and that heat and moisture
      play a minor role. The need for a standard, highly stringent positive control for
      screening synthetic attractants is strongly highlighted.

PMID- 20051144
TI  - A comparison of SNP and STR loci for delineating population structure and
      performing individual genetic assignment.
AB  - BACKGROUND: Technological advances have lead to the rapid increase in
      availability of single nucleotide polymorphisms (SNPs) in a range of organisms,
      and there is a general optimism that SNPs will become the marker of choice for a
      range of evolutionary applications. Here, comparisons between 300 polymorphic
      SNPs and 14 short tandem repeats (STRs) were conducted on a data set consisting
      of approximately 500 Atlantic salmon arranged in 10 samples/populations. RESULTS:
      Global FST ranged from 0.033-0.115 and -0.002-0.316 for the 14 STR and 300 SNP
      loci respectively. Global FST was similar among 28 linkage groups when averaging
      data from mapped SNPs. With the exception of selecting a panel of SNPs taking the
      locus displaying the highest global FST for each of the 28 linkage groups, which
      inflated estimation of genetic differentiation among the samples, inferred
      genetic relationships were highly similar between SNP and STR data sets and
      variants thereof. The best 15 SNPs (30 alleles) gave a similar level of self
      assignment to the best 4 STR loci (83 alleles), however, addition of further STR
      loci did not lead to a notable increase assignment whereas addition of up to 100
      SNP loci increased assignment. CONCLUSION: Whilst the optimal combinations of
      SNPs identified in this study are linked to the samples from which they were
      selected, this study demonstrates that identification of highly informative SNP
      loci from larger panels will provide researchers with a powerful approach to
      delineate genetic relationships at the individual and population levels.

PMID- 20051145
TI  - [The cause of death of Theo van Gogh (1857-1891)].
AB  - In 1992 Theo van Gogh's medical files from the Willem Arntsz Huis, a psychiatric
      centre in Utrecht, the Netherlands, were made available. A study based on two
      copies of these files was published in this journal earlier. While reviewing the
      archives, the author noticed a third copy which included an extra (last) page
      that was missing in the other two copies. This page provided medical information
      regarding Theo van Gogh's final days. Based on this new information the present
      article corrects some misconceptions about his death. For example, it is commonly
      thought that Theo had uraemia or, like his brother Vincent the painter (1853
      1890), committed suicide. This new information demonstrates that this is not the
      case. The extra page, dated 26 January 1891, shows that on the two days before he
      died Theo suffered two epileptic fits, most probably symptomatic to his dementia
      paralytica. After the second fit he did not regain consciousness. Heartbeat and
      respiration gradually weakened and he passed away on January 25th at eleven
      thirty P.M. Other symptoms mentioned were vomiting, fever and early signs of
      decubitus. The family did not give permission for a post-mortem.

PMID- 20051146
TI  - [Chylous ascites].
AB  - A 49-year-old female presented in a casualty department with acute abdomen. The
      CT scan revealed an extensive build-up of peritoneal and retroperitoneal fluid.
      Laparotomy revealed chylous ascites in the abdominal cavity. The patient made a
      successful recovery following treatment with total parenteral nutrition. No cause
      of the chylous ascites was found. Extensive diagnostics are indicated in adults
      with chylous ascites without a history of surgery as the most common cause of the
      condition in this group is malignant lymphoma. Treatment is targeted at a good
      nutritional status, lowering chylous production and treating the underlying
      causes.

PMID- 20051147
TI  - [Focal liver lesion after normal pregnancy].
AB  - Two months after a normal pregnancy, a 27-year-old woman presented with a focal
      liver lesion, which was first interpreted on CT as 'multiple liver cell
      adenomas'. 2 months later, it turned out to be a metastasis of a choriocarcinoma.
      This rare neoplasm will often be omitted from the differential diagnosis of liver
      lesions found during or after pregnancy. However, it is important not to miss
      this diagnosis since choriocarcinoma metastasis can be successfully treated.
      Therefore, it is advisable when focal liver lesions are found in women of child
      bearing age also to measure human chorionic gonadotropin (hCG) serum
      concentration.

PMID- 20051149
TI  - [Summary of the practice guideline 'Prevention and early diagnosis of cervical
      cancer' of the Dutch College of General Practitioners].
AB  - A persistent infection with human papillomavirus (HPV) underlies all cases of
      cervical cancer. HPV testing is repeated 6 months after initial Pap smears 2 or
      3a1. As vaccination against HPV is now included in the National Immunisation
      Programme of the Netherlands, yearly cervical cancer morbidity and mortality
      rates are expected to be cut by half. After vaccination against HPV, women still
      need to participate in the cervical cancer screening programme. Breastfeeding is
      no longer a contraindication for making Pap smears, provided that breastfeeding
      is indicated on the cytology application form. Liquid-based cervical cytology is
      an equivalent to conventional cervical cytology and offers the possibility of
      testing for HPV. General practitioners are responsible for communicating results
      from the cervical cancer screening programme to the participating women.

PMID- 20051150
TI  - [Summary of Dutch College of General Practitioners guidelines on "Rectal
      bleeding"].
AB  - Rectal bleeding is often caused by a harmless disorder such as haemorrhoids or an
      anal fissure, but may be a symptom of colorectal cancer or inflammatory bowel
      disease. Risk factors for colorectal cancer are: older age (arbitrary > 50
      years), a first-degree relative aged < 70 years with colorectal cancer, change in
      bowel habit, blood mixed with stools and the absence of anal or perianal
      symptoms. Colonoscopy should be performed when colorectal cancer is suspected.
      Treatment of haemorrhoids and anal fissures by the general practitioner
      especially includes education, treatment of comorbidity and, if necessary, local
      treatment. Proctoscopy is feasible in general practice.

PMID- 20051151
TI  - [Guideline 'Diagnosis and treatment of abdominal aortic aneurysm'].
AB  - The evidence-based guideline 'Diagnosis and treatment of abdominal aortic
      aneurysm' is applicable to all patients with an atherosclerotic fusiform or
      ruptured aneurysm of the abdominal aorta (AAA) and can be found on www.vaat
      chirurgie.nl, click on Richtlijnen. An AAA with a diameter < 5.5 cm is treated
      conservatively and monitored by sonographic surveillance. All patients are
      advised secondary prevention with antiplatelet therapy, a statin, treatment of
      hypertension and smoking cessation. Depending on comorbidity, the indication for
      an operation is an AAA diameter of 5.5 cm. The anatomical characteristics of the
      AAA guides the choice for an open operation or endovascular aneurysm repair
      (EVAR). In view of the lower perioperative mortality, EVAR is the treatment of
      choice. Due to the high prevalence of AAA in siblings of patients with an AAA the
      screening of these family members should be considered. The minimum number of
      elective operations per hospital per year has been set at 15.

PMID- 20051153
TI  - [Practice guideline 'Pharmaceutical pain treatment during labour'; the woman's
      request is sufficient indication].
AB  - The basic principle of the practice guideline 'Pharmaceutical pain treatment
      during labour' is that during labour every woman can have adequate pain treatment
      at her request. Most women experience severe pain during labour, but
      retrospective satisfaction also depends on the support of care-givers and on the
      extent to which the woman was involved in decisions relating to her situation. A
      number of medical indications require good pain management. Epidural analgesia is
      the safest and most effective method, preferably as patient-controlled analgesia
      (PCA). PCA with remifentanil appears promising, but remains to be adequately
      investigated. Pethidine is far less effective. Recommended organisational changes
      include structured provision of information on pharmaceutical pain management in
      the 30th week of pregnancy, to be developed by midwives, obstetricians and
      anaesthetists. Other recommended changes include referral to another hospital for
      the treatment of choice, development of local protocols across primary and
      secondary care with agreements about out-patient referral to the anaesthetist,
      structured daily contact between obstetricians and anaesthetists, the time lapse
      between the request for pain treatment and the administration of the treatment,
      and the site of administration and monitoring.

PMID- 20051154
TI  - [Interstitial pneumonitis as an adverse effect of thalidomide].
AB  - A 67-year-old man was admitted to the hospital with symptoms of progressive
      dyspnoea. For 2 months he had received second-line treatment with dexamethasone
      and thalidomide for a multiple myeloma. Physical examination revealed a
      tachypnoeic patient and arterial blood gas analysis revealed a respiratory
      alkalosis and severe hypoxaemia. A high-resolution CT scan showed diffuse ground
      glass opacities in both lungs. Pulmonary function testing indicated severe
      diffusion capacity impairment. Bronchoalveolar lavage and cultures excluded the
      possibility of an infectious agent. The thalidomide treatment was discontinued
      whereupon the hypoxaemia and the ground glass opacities resolved and the
      diffusion capacity impairment improved. When a patient treated with thalidomide
      presents with dyspnoea and hypoxaemia with ground glass opacities, thalidomide
      induced pneumonitis should be considered. Withdrawing thalidomide is the only
      treatment.

PMID- 20051156
TI  - [Multidisciplinary guidelines for 'Apparent life threatening event' (ALTE)].
AB  - In order to reach a consensus concerning diagnosis, support and follow-up in
      children with an 'apparent life threatening event' (ALTE) multidisciplinary
      guidelines have been developed by the Dutch Paediatric Association and the Dutch
      Institute for Healthcare Improvement (CBO). All children presenting as an
      emergency with ALTE should undergo inpatient clinical observation for 24-72 h,
      with at least 24 h of cardio-respiratory monitoring. Observation does not need to
      be continued once an explanation for the incident has been established. The most
      common causes of ALTE are: gastro-oesophageal reflux (31%), neurological insult
      (11%) and lower respiratory tract infection (8%). Results from a targeted case
      history and from physical and neurological examination serve as a guideline for
      further investigations and support, in accordance with the formulated flowchart.
      A complete blood-count, CRP- and glucose concentration determination, blood-gas
      analysis and exploratory urine analysis should be carried out in all infants
      admitted with an ALTE, and an acute phase urine sample should be collected and
      frozen for possible metabolic investigation at a later date. Routine monitoring
      at home is not recommended following an ALTE.

PMID- 20051158
TI  - [Sleep disorders and the ability to drive, revision of legislation].
AB  - Professional truck drivers suffering from obstructive sleep apnoea syndrome
      (OSAS) are more often involved in traffic accidents. OSAS can be treated
      successfully and the effects of treatment are visible almost immediately.
      Treatment of OSAS has shown a significant reduction in the number of traffic
      accidents. Based on criteria for effective treatment, the requirements for the
      ability to drive have recently been modified by ministerial decree. The period
      during which persons with OSAS were not allowed to drive was formerly at least 1
      year for a passenger car and 5 years for a truck or bus. The period has now been
      reduced to 2 and 3 months respectively. Legislation has also been adjusted for
      drivers with narcolepsy and idiopathic hypersomnia for whom the use of
      psychostimulant drugs is allowed. The modified legislation is intended to prevent
      underdiagnosis, may improve driving safety and is in the public interest.

PMID- 20051159
TI  - [Guideline 'Medicinal care for drug addicts in penal institutions'].
AB  - In the Netherlands, the policy on care for prisoners who are addicted to opiates
      is still heterogeneous. The recent guidelines entitled 'Medicinal care for drug
      addicts in penal institutions' should contribute towards unambiguous and more
      evidence-based treatment for this group. In addition, it should improve and bring
      the care pathways within judicial institutions and mainstream healthcare more
      into line with one another. Each rational course of medicinal treatment will
      initially be continued in the penal institution. In penal institutions the help
      on offer is mainly focused on abstinence from illegal drugs while at the same
      time limiting the damage caused to the health of the individual user. Methadone
      is regarded at the first choice for maintenance therapy. For patient safety, this
      is best given in liquid form in sealed cups of 5 mg/ml once daily in the morning.
      Recently a combination preparation containing buprenorphine and naloxone - a
      complete opiate antagonist - has become available. On discontinuation of opiate
      maintenance treatment intensive follow-up care is necessary. During this period
      there is considerable risk of a potentially lethal overdose. Detoxification
      should be coupled with psychosocial or medicinal intervention aimed at preventing
      relapse. Naltrexone is currently the only available opiate antagonist for
      preventing relapse. In those addicted to opiates, who also take benzodiazepines
      without any indication, it is strongly recommended that these be reduced and
      discontinued. This can be achieved by converting the regular dosage into the
      equivalent in diazepam and then reducing this dosage by a maximum of 25% a week.

PMID- 20051160
TI  - [Neuraminidase inhibitors and high risk of influenza complications: considered
      and widely-supported recommendations].
AB  - It has been suggested that it is unwise to employ neuraminidase inhibitors in
      order to diminish the risk of influenza-related complications in cases of
      infection with the new influenza A(H1N1). However, the major argument, i.e. that
      the beneficial effects shown in the published evidence may be due to age
      differences between treatment and placebo groups, can easily be refuted. The
      Netherlands' policy to limit treatment to those patient groups who are considered
      at high risk of influenza complications is a sound one. In addition, it is
      endorsed by recent guidelines of the WHO and CDC.

PMID- 20051161
TI  - [Practice guideline 'Diagnosis and treatment of rheumatoid arthritis'].
AB  - Treatment early in the course of the disease, along with early diagnosis, has a
      positive influence on clinical outcome in patients with rheumatoid arthritis
      (RA). Therapeutic strategies, including the use of 'disease-modifying
      antirheumatic drug' (DMARD) combinations, have proved effective, with relatively
      few side effects. New insights into the pathophysiology of RA have lead to the
      development of novel therapeutic agents that have been demonstrated to be highly
      effective. Patients should be monitored intensively with respect to the effect of
      therapy on reduction of disease activity, followed by modification of therapeutic
      strategy in the case of a suboptimal treatment response. Various non
      pharmacological interventions, such as exercise therapy and patient education,
      are available to help patients to cope with the consequences of the disease.
      Optimizing treatment of RA by means of this approach will help to realize the
      goal of current therapy: to achieve and sustain remission and, thereby, an
      optimal functional level.

PMID- 20051162
TI  - [Guideline on urothelial carcinoma of the bladder].
AB  - Urothelial carcinoma of the bladder is diagnosed predominantly in people over 60
      years of age. The most common symptom is haematuria. Smoking is an important risk
      factor (relative risk 2.5 to 3). Cystoscopy is performed whenever bladder
      carcinoma is suspected. The recurrence rate of a non-muscle invasive urothelial
      carcinoma is high (31-78% within 5 years). A single intravesical instillation
      with a chemotherapeutic agent within 24 hours of transurethral resection (TUR)
      reduces the risk of recurrence. Carcinoma in situ (CIS) should be treated as high
      grade urothelial carcinoma. Standard treatment for patients with non-metastasized
      muscle-invasive urothelial carcinoma is cystectomy in combination with extensive
      lymph node dissection. There are several possibilities for urinary diversion
      following cystectomy, none of which are any better than the others. Bladder
      sparing brachytherapy may be used in patients with solitary T1 - T2 urothelial
      carcinoma < 5 cm. Neoadjuvant cisplatin-containing chemotherapy prior to
      cystectomy in muscle-invasive carcinoma only slightly improves survival.
      Cisplatin-containing combination chemotherapy is the standard treatment for
      metastasized urothelial carcinoma.

PMID- 20051163
TI  - [Ogilvie Syndrome induced by clozapine].
AB  - Clozapine is an antipsychotic drug which is used in the treatment of therapy
      resistant schizophrenia. The most frequently reported side effects (occurring in
      more than 10% of patients) are gastro-intestinal complaints, including
      constipation. Here we describe the case of a 28-year-old man with schizophrenia
      who developed constipation and abdominal distension for several weeks while
      taking clozapine. He was admitted as an emergency suffering from clozapine
      induced Ogilvie syndrome (acute pseudo-obstruction caused by a disturbed balance
      in the autonomic regulation of intestinal motility). Treatment on the intensive
      care unit was required because of septic shock and multiple organ dysfunction
      syndrome. Colonoscopy showed severe ischaemic colitis without signs of
      perforation or obstruction. Because conservative treatment with enemas,
      prokinetic drugs and antibiotics did not have sufficient effect, the cholinergic
      drug neostigmine was added to the treatment regimen. This led to a good clinical
      response, thereby averting the need for surgery. This case illustrates that
      decreased intestinal motility can be a severe problem for patients taking
      clozapine, which may lead to life-threatening complications.

PMID- 20051165
TI  - [Tick-borne encephalitis after a holiday in Southern Germany].
AB  - A 56-year-old man was admitted to hospital with complaints of headache, fever and
      photophobia, 3 weeks after being bitten by ticks in Southern Germany. Two weeks
      before admission he had experienced a short period of a flu-like illness, from
      which he spontaneously recovered. Based on the tick bites in Southern Germany and
      the biphasic course of the illness shortly afterwards, we made the diagnosis tick
      borne encephalitis, Fruhsommer-Meningoenzephalitis in German (FSME). The
      diagnosis was confirmed serologically. FSME is caused by a flavivirus, which is
      transmitted via tick bites. In 72-87% of cases the course is biphasic. The virus
      subtype and the degree of central nervous system involvement determine the
      prognosis. The patient may experience residual symptoms. The treatment is
      symptomatic. Active immunisation offers protection, but is only recommended to
      those who stay frequently or for a long period in areas where the virus is
      endemic.

PMID- 20051166
TI  - [A boy with oral vesicles and cutaneous lesions].
AB  - A 9-year-old boy had oral vesicles and cutaneous lesions due to hand foot and
      mouth disease.

PMID- 20051167
TI  - [The Dutch College of General Practitioners' practice guideline on arthritis].
AB  - The Dutch College of General Practitioners' new practice guideline on arthritis
      combines arthritis and gout. One of the important improvements in this guideline
      is that it recommends that patients be referred to the rheumatologist as soon as
      4 weeks after being seen, or earlier, if rheumatoid arthritis is likely or
      suspected. Obviously, these early referrals are related to the large increase in
      effective treatment options in rheumatoid arthritis, particularly after early
      treatment (window of opportunity). The new guideline relating to gout advocates
      the use of oral prednisone as the second choice in patients without an adequate
      treatment response or who do not tolerate NSAIDs: colchicine and intra-articular
      injections may be attractive alternatives.

PMID- 20051169
TI  - [Azole-resistant invasive aspergillosis].
AB  - Invasive aspergillosis caused by medical triazole-resistant Aspergillus fumigatus
      is described in two patients. A 31-year-old male with chronic granulomatous
      disease developed pulmonary aspergillosis despite itraconazole prophylaxis. A.
      fumigatus was cultured from the lung and was found to be azole-resistant. The
      patient was successfully treated with caspofungin. The second patient was a 13
      year-old boy with acute lymphoid leukaemia. He developed pulmonary aspergillosis
      that failed to respond to voriconazole therapy. The infection spread to the brain
      and an azole-resistant isolate was cultured from a lung biopsy. Despite a switch
      to liposomal amphotericin B in combination with caspofungin, the infection
      progressed and the patient died. Azole-resistance has emerged in A. fumigatus and
      may develop through the treatment of patients. However, there is evidence that in
      the Netherlands, resistance might be emerging through fungal exposure to azole
      fungicides. Azole resistance further complicates the management of invasive
      aspergillosis and should be considered as cause for treatment failure.

PMID- 20051170
TI  - [Management and treatment of pregnant women with hepatitis B].
AB  - Every year about 800 chronic hepatitis B infections are identified in the
      Netherlands as result of the nationwide pregnancy screening. About one-third of
      these are newly discovered infections. In recent years there has been a marked
      increase in treatment options for chronic hepatitis B infection using antiviral
      drugs. Pregnant women can now be treated as well. A pregnant woman with a low
      viral load does not require immediate treatment, as due to the passive
      immunisation and active vaccination of the newborn the chances of infection due
      to perinatal transmission are negligible. Treatment of the mother can therefore
      be postponed until after the birth. However, when the pregnant woman has a high
      viral load (>10(9) copies/ml in serum), perinatal transmission can still occur
      despite vaccination of the newborn. In these women, antiviral treatment in the
      last trimester of the pregnancy should be considered. At present, experience of
      treating HBV-infected pregnant women has only been gained with lamivudine. It
      appears that the quantity of circulating virus decreases due to the treatment.
      Treatment should always be supervised by a gastroenterologist or an
      infectiologist. Detection, referral and treatment of the mother and child are
      described in several guidelines that have recently been updated and harmonized
      with each other. These include a practice guideline from the Dutch College of
      General Practitioners, a guideline from the Centre for Infectious Disease Control
      of the National Institute for Public Health and the Environment, and a guideline
      from the Netherlands Society of Gastroenterology.

PMID- 20051171
TI  - [IGZ report on the PROPATRIA study: lessons from the study].

PMID- 20051172
TI  - [PROPATRIA and safety in clinical trials. Comments on the IGZ-CCMO-VWA-raport].

PMID- 20051173
TI  - [Heart and evolution--form and function of all mammalian hearts are identical].
AB  - The 200th anniversary of the birth of Charles Darwin this year (2009) is a
      perfect reason to focus on the evolution of the mammalian heart. All life on
      earth is the result of a process called evolution. The human being is a product
      of evolution and has all the characteristics of a mammal. Size, form and function
      of the mammalian heart may be viewed in relation to evolution. All morphological
      and functional properties of the heart in all currently existing mammalian
      species are practically identical. This implies that during the eons in which all
      mammals had to adapt to climate and geological changes by which they
      differentiated into almost limitless varieties, whether they be mice, whales or
      humans, the heart hardly, if at all, participated in this process and remained
      unaffected. This must lead to the conclusion that the heart of the first mammals
      on earth was already well equipped to fulfil the functional demands of all future
      mammalian species.

PMID- 20051174
TI  - [Comfort after a sad outcome of pregnancy. Two letters of Frederick the Great to
      Wilhelmina of Prussia].
AB  - After her unfortunate experience of parturition Princess Wilhelmina of Prussia,
      married to stadhouder Prince Willem V, received two letters of comfort from her
      beloved godfather King Frederick II (Frederick the Great) of Prussia. These
      letters illustrate the special close connection there was between them. The
      letters also give a view on the difficult question of giving comfort after
      perinatal death.

PMID- 20051175
TI  - [Professor Pel and 'glandular fever'].
AB  - Pieter Klaesz Pel (1852-1919) was professor of internal medicine at the
      University of Amsterdam, for more than 35 years. His name - and that of Ebstein -
      is linked to periodic fever in combination with enlargement of the spleen and the
      lymphatic system. It is contested whether the patients in question had Hodgkin's
      disease.

PMID- 20051176
TI  - [Pseudologia fantastica. Recognition and treatment of pathological lying].
AB  - Although a clear definition of pseudologia fantastica cannot be found in the
      literature, there is consensus that this condition differs quantitatively and
      qualitatively from 'normal lying'. We discuss recognition of pseudologia
      fantastica based on 2 patients who presented with suicidal ideations at the
      casualty department following a traumatic event. Early recognition is important
      in order to break the pattern of lying, to restrict the use of medical resources
      and, finally, to act in accordance with the general principle of 'primum-non
      nocere'. Although a psychiatric diagnostic workup might be worthwhile, it remains
      difficult to engage these patients for psychiatric treatment.

PMID- 20051177
TI  - [Diagnostic image. A man with a swelling under his jaw].
AB  - A 79-year-old man had a tumour under his jaw, due to tuberculosis in a lymph node
      following BCG treatment for carcinoma of the bladder.

PMID- 20051178
TI  - [Fireworks injuries treated by Dutch ophthalmologists New Year 2008/'09].
AB  - OBJECTIVE: To list and describe eye injuries caused by consumer fireworks around
      New Year 2008/'09. DESIGN: Descriptive study. METHODS: All members of the
      Netherlands Society of Ophthalmology (NOG) were called upon by the board to
      register all the firework-related eye injuries they treated between 27 December
      2008 and 4 January 2009. As well as several details about the patient, type of
      firework, nature of the accident, type and severity of injury, and treatment were
      registered. RESULTS: In total, 95% of ophthalmologists on duty at the turn of the
      year sent in registration forms. They treated and registered a total of 268
      patients with 315 eye injuries caused by fireworks. 56 % of patients were
      bystanders. Most victims were male. 59% (n = 158) of patients were minors (3-17
      years); the majority were 10-15-year-old boys. One third of the eyes (n = 99)
      sustained permanent damage. In 47 eyes the extent of the damage was such that it
      led to irreversible loss of vision, and in 24 eyes to complete loss of vision. 15
      of these 24 eyes were surgically removed. 'Bangers' caused most injuries, but
      rockets caused the most serious injuries. CONCLUSION: On medical grounds the NOG
      believes that the current policy of tolerance regarding fireworks makes the risk
      of eye injuries to which the Dutch population is exposed, too high. As long as
      consumer fireworks are allowed, the NOG advises that protective polycarbonate
      glasses be worn while lighting and watching of fire-works.

PMID- 20051179
TI  - [Voices from the past: castrate singers].
AB  - Castration is a severely mutilating procedure. In Italy in the period around 1600
      1850 even up to 4,000 yearly prepubescent boys per year underwent a bilateral
      orchidectomy to preserve their boyish high voice in order to become a 'castrato'
      singer. The operation was not without health risks and must have caused severe
      psychological problems, but some of the victims would become very famous, such as
      Carlo Broschi (1705-1782), better known as Farinelli. However, the majority of
      the castrati would remain unknown. Tradition has it that that the castrati were
      welcomed with euphoria by the general public. The last castrato at the Vatican,
      Alessandro Moreschi, died in 1922. The surviving recordings of the voice of this
      last official castrato give an impression of how the castrati's singing may have
      sounded. Several attempts have been made since to imitate the sound of the
      castrati, for example by digitally mixing soprano and countertenor voices.

PMID- 20051180
TI  - [Hospital in Arles].
AB  - During his stay in the south of France, Van Gogh had a fight with his friend
      Gauguin. This resulted in Van Gogh being admitted to the Arles hospital, where he
      painted two paintings.

PMID- 20051181
TI  - [Extra-mammary Paget's disease of the scrotum].
AB  - An 82-year-old man presented with an itching rash on his scrotum that he had had
      for several years. Histopathological examination revealed a normal epidermis with
      multiple atypical cells, organised both solitary and group-wise within the
      epidermis. The diagnosis of extra-mammary Paget's disease (EMPD) was made.
      Further investigation showed no signs of underlying malignancy. The man was
      operated upon and the lesion was completely removed. EMPD is an intra-epidermal
      adenocarcinoma, found in areas with apocrine sweat glands. Primary EMPD (75%)
      probably arises from pluripotent stem cells in the epidermis. Over time it can
      invade the dermis and deeper tissues and metastasize. In secondary EMPD (25%)
      there is epidermal invasion of malignant cells of skin adnexal adenocarcinomas,
      or there is an association with adenocarcinomas of nearby internal organs.
      Immunohistochemical investigation may help to discriminate between primary and
      secondary EMPD. Average mortality is 26%. Treatment depends on the presence of an
      underlying malignancy, but surgery is the preferred option. The risk of relapse
      varies from 8 to 61%, which makes a long-term follow-up necessary.

PMID- 20051182
TI  - [Secondary use of human tissue: consent and better information required].
AB  - Human tissue remaining after diagnostic procedures is important for use in
      scientific research. This 'secondary use' of tissue is regulated by the Dutch
      Medical Treatment Contracts Act and the Code of Conduct for Proper Secondary Use
      of Human Tissue of the Dutch Federation of Biomedical Scientific Societies.
      Patients have the right to opt-out of further use of their residual tissue, but
      the procedures for objection and the provision of information involved are not
      regulated by statute. Dutch patients have a positive attitude to further use of
      human tissue for other purposes. They prefer, however, a procedure in which they
      are informed verbally by their health professional about research with residual
      tissue. The information can be brief and is best provided early in the treatment.
      Administrative and technical modifications of the current registration systems
      are necessary to support the opting-out procedure in practice. By taking the
      preferences of patients into account, trust in medical practice can be
      maintained.

PMID- 20051183
TI  - Evaluating the effects of implementation intention and self-concordance on
      behaviour.
AB  - The purpose of the present study was to investigate effects of implementation
      intentions on taking one multivitamin tablet, everyday, for 2 weeks, among
      individuals who endorsed self-concordant and self-discordant forms of motivation.
      A 2 (implementation intentions: yes, no) * 3 (motivation: self-concordance, self
      discordance, control) experimental design was adopted with university students
      being exposed to manipulations of implementation intentions, self-concordance,
      and self-discordance (male = 110, female = 120, M age = 23.50 years, SD = 7.21).
      Results of the study indicated that while implementation intentions increased
      multivitamin intake for individuals who endorsed self-concordant and self
      discordant forms of motivation, the combination of self-concordance and
      implementation intentions produced particularly enhanced levels of compliance on
      multivitamin intake. The implications of results of the present study to theory
      development and practice are discussed.

PMID- 20051185
TI  - Current state and future possibilities for ambient intelligence to support
      improvements in the quality of health and social care.

PMID- 20051186
TI  - Health-related decision making: the use of information giving models in different
      care settings.

PMID- 20051187
TI  - Providing quality primary care in the Caribbean.

PMID- 20051189
TI  - Does appraisal enhance learning, improve practice and encourage continuing
      professional development? A survey of general practitioners' experiences of
      appraisal.
AB  - BACKGROUND: Revalidation of the medical profession is under review and a system
      has been proposed to ensure doctors meet standards of practice and
      professionalism. The current appraisal system allows clinicians to chart their
      progress and identify developmental needs in order to improve performance.
      Appraisal is now an annual compulsory requirement for all doctors. AIM AND
      OBJECTIVES: The aim of the study was to investigate the experiences of general
      practitioners (GPs) of the current appraisal process. The specific objectives
      were to consider the impact the appraisal process had exerted on their learning,
      practice and individual continuing professional development (CPD). METHODS: We
      employed a cross-sectional design using a postal questionnaire sent to all
      doctors who work as GPs (n = 385) in West Kent. MAIN RESULTS: Questionnaires were
      returned from 71.7% of doctors (n = 276). The key findings obtained were that
      47.5% (n = 131) of doctors stated that taking part in the appraisal process had
      enhanced their learning, 40.2% (n = 111) felt that the appraisal process had
      improved their practice and 55.8% (n = 154) stated that the appraisal process had
      encouraged their CPD. Qualitative findings derived from thematic analysis of open
      questions revealed that participants viewed the role of the appraiser as
      respected peer to be vital and there was a need for independence in the
      appraiser's appointment. The time-consuming nature of the appraisal process was
      emphasised, with little protected time for preparation of documentation and
      engagement in CPD. Concerns were expressed about links between appraisal and
      revalidation. CONCLUSIONS: Many doctors considered that the appraisal process had
      enhanced their learning, improved their practice and encouraged their CPD. A
      vital, independent role for the appraiser was emphasised as was a need to review
      the time-consuming nature of the current appraisal process, together with
      identifying protected time to complete this and CPD engagement. As the role of
      appraisal within the revalidation process changes it is recognised that ensuring
      the quality, consistency and nature of appraisal will be essential to maintain
      the confidence of patients and doctors.

PMID- 20051190
TI  - Impact of patient education on quality of bowel preparation in outpatient
      colonoscopies.
AB  - BACKGROUND: High-quality bowel preparation is essential for successful outpatient
      colonoscopy. Currently, the rate of adequate bowel preparation for outpatient
      colonoscopy in the USA is low. Patients often fail to adhere to recommended
      preparation instructions. Limited literature exists on evaluating educational
      intervention as a means of improving the quality of bowel preparation prior to
      outpatient colonoscopy. OBJECTIVE: Our objective was to determine the effect of
      an educational intervention on the quality of outpatient colonoscopy preparation.
      The secondary objective was to determine whether the quality of bowel preparation
      improves overall colonoscopy outcomes as measured by rate of polyp detection and
      caecal intubation time. METHODS: A single-blinded, prospective, randomised,
      controlled trial was conducted in two inner-city gastroenterology clinics in the
      USA. One hundred and sixty-four subjects were enrolled and randomly assigned to
      one of two groups. The control group subjects received verbal and written
      instructions for colonoscopy. The intervention group subjects received the same
      instructions and were then asked to answer a questionnaire. The subjects'
      responses were reviewed and an additional explanation of the preparation process
      provided. An attending gastroenterologist determined the quality of each bowel
      preparation at the time of colonoscopy using the Universal Preparation Assessment
      Scale. RESULTS: The educational intervention had no impact on the overall quality
      of bowel preparation (P=0.12). However, the type of food (liquid vs solid)
      consumed during the 24 hours prior to the procedure (P=0.04) and the time since
      the last solid meal (P=0.03) did have an impact on preparation quality. Other
      significant factors included elapsed time to first bowel movement from the
      initiation of bowel preparation (P=0.05) and age younger than 55 (P=0.02).
      Adequate bowel preparation was associated with shorter total procedure (P=0.001)
      and caecal intubation (P=0.01) times. CONCLUSION: Our study failed to demonstrate
      any effect of an educational intervention on the quality of colonoscopy
      preparation. However, adherence to simple dietary instructions did have a
      significant impact on the quality of bowel preparation. Adequate bowel
      preparation was associated with shorter procedure time and caecal intubation
      time.

PMID- 20051191
TI  - Back pain management in primary care: patients' and doctors' expectations.
AB  - BACKGROUND: Expectations may be a key element for improving quality of health
      care, yet several barriers interfere with understanding and optimising
      expectations in back pain primary care. OBJECTIVE: To review the literature
      related to expectations, back pain patients' and doctors' expectations and
      sources of unmatched expectations. METHODS: Review of qualitative and
      quantitative studies investigating back pain management in primary care settings,
      and eliciting patients' and/or doctors' pre-visit or post-visit expectations.
      RESULTS: Reviewing the literature reveals that expectations are defined and
      conceptualised in various ways, with several terms used interchangeably, which
      suggests a lack of clear definition and conceptual framework. Patients have a
      wide range of specific expectations for care, which can be measured, and may play
      a vital role in their satisfaction: doctors also seem to have their own
      expectations. However, studies of such expectations are scarce and there is a
      lack of valid measurement tools to capture such aspects. DISCUSSION: Shortcomings
      in literature included the use of different meanings and definitions for
      expectations, which interfered with understanding the results of previous
      research. Previous studies focused on patients' general rather than condition
      specific expectations; no study explored doctors' expectations or the congruency
      between patients' and doctors' back pain-specific expectations. CONCLUSIONS:
      There is a need for standardisation of definition in expectations research and a
      valid measurement tool that is condition specific. Understanding patients' and
      doctors' expectations may be a key factor for improving quality of care, in terms
      of both process and outcome.

PMID- 20051192
TI  - The anatomy, physiology and pathogenesis of a significant untoward incident.
AB  - This paper provides a structured chronology of an investigation into a
      significant untoward incident in an elderly care ward. Using Reason's Swiss
      Cheese Model, which has become one of the dominant paradigms for analysing
      clinical and patient safety incidents, it charts the interplay of national and
      local policies resulting in unsafe practice. A qualitative approach was used in
      this multidimensional investigation. This approach aimed to discover what
      actually happened in the specific and related incidents and the underlying
      causes. Thus, the anatomy of the incident refers to the structure of staffing,
      the physiology includes the process in place at the time of the incident and the
      pathogenesis alludes to the development of the incident. The findings report on
      the patients involved in the incident. The investigation also explores how
      strategic financial directions from the Department of Health impact on staffing
      levels and training. These are contextualised using the concepts of the Swiss
      Cheese Model to assist understanding of how and why the incident occurred. Key
      points emanating from a learning event are captured to aid understanding and the
      importance of being cognisant of the ever present risks in clinical practice. The
      impact of the investigation on staff and the primary care trust are also
      presented.

PMID- 20051193
TI  - The Torfaen referral evaluation project.
AB  - BACKGROUND: This paper provides an overview of the Referral Evaluation Project,
      which took place in South East Wales, UK during 2007-2008. AIM: To engage general
      practitioners (GPs) and consultants in the local hospitals of Gwent Healthcare
      Trust in discussions as to the validity, quality and appropriateness of GPs'
      referrals and to increase the quality of those referrals. To discuss with other
      healthcare professionals the use of community-based services, which could be used
      instead of referral to hospital. METHOD: A year-long scheme whereby GPs were
      funded for weekly protected time to discuss their referrals retrospectively by
      peer review, and to attend six-weekly cluster meetings where representatives from
      the practices met with consultants to discuss the appropriateness of those
      referrals and the use of alternative community-based services. Referral data were
      fed back to the practices by personnel from the local health board (LHB). The
      evaluation involved three practices in Torfaen, South East Wales; Torfaen LHB
      staff, consultants in Gwent Healthcare Trust, and other health professionals. The
      main outcomes used were indicators of referral quality as judged by the GPs,
      referral rates to hospital orthopaedics and emergency admissions, and evidence of
      increased use of community-based services. RESULTS: The quality of referrals as
      judged by doctors' peers improved. Referral rates in orthopaedics and emergency
      admissions showed a striking reduction by up to 50%, variability between
      practices decreased, and referrals to local services increased. Alternative
      community-based services were explored and an understanding of the best local
      pathways for some common conditions was reached. CONCLUSION: This approach was
      felt to be a more sustainable and more intuitive method of improving the quality
      of referrals and reducing inappropriate demand compared to other approaches, for
      example, conventional referral management centres.

PMID- 20051194
TI  - Primary care and care for chronic cancer patients in Europe: position paper of
      the European Forum for Primary Care.

PMID- 20051195
TI  - Scientific editors' report: volume 72 - December 31, 2009.

PMID- 20051196
TI  - "Campylobacter transfer from naturally contaminated chicken thighs to cutting
      boards is inversely related to initial load," a comment on: J. Food Prot. 72(9):
      1836-1840 (2009).

PMID- 20051198
TI  - Control of Salmonella on sprouting mung bean and alfalfa seeds by using a
      biocontrol preparation based on antagonistic bacteria and lytic bacteriophages.
AB  - The following reports on the application of a combination of antagonistic
      bacteria and lytic bacteriophages to control the growth of Salmonella on
      sprouting mung beans and alfalfa seeds. Antagonistic bacteria were isolated from
      mung bean sprouts and tomatoes by using the deferred plate assay to assess anti
      Salmonella activity. From the isolates screened, an Enterobacter asburiae strain
      (labeled "JX1") exhibited stable antagonistic activity against a broad range of
      Salmonella serovars (Agona, Berta, Enteritidis, Hadar, Heidelberg, Javiana,
      Montevideo, Muenchen, Newport, Saint Paul, and Typhimurium). Lytic bacteriophages
      against Salmonella were isolated from pig or cattle manure effluent. A
      bacteriophage cocktail prepared from six isolates was coinoculated with E.
      asburiae JX1 along with Salmonella in broth culture. The combination of E.
      asburiae JX1 and bacteriophage cocktail reduced the levels of Salmonella by 5.7
      to 6.4 log CFU/ml. Mung beans inoculated with Salmonella and sprouted over a 4
      day period attained levels of 6.72 + or - 0.78 log CFU/g. In contrast, levels of
      Salmonella were reduced to 3.31 + or - 2.48 or 1.16 + or - 2.14 log CFU/g when
      the pathogen was coinoculated with bacteriophages or E. asburiae JX1,
      respectively. However, by using a combination of E. asburiae JX1 and
      bacteriophages, the levels of Salmonella associated with mung bean sprouts were
      only detected by enrichment. The biocontrol preparation was effective at
      controlling the growth of Salmonella under a range of sprouting temperatures (20
      to 30 degrees Celsius) and was equally effective at suppressing the growth of
      Salmonella on sprouting alfalfa seeds. The combination of E. asburiae JX1 and
      bacteriophages represents a promising, chemical-free approach for controlling the
      growth of Salmonella on sprouting seeds.

PMID- 20051199
TI  - Development of multitarget real-time PCR for the rapid, specific, and sensitive
      detection of Yersinia pestis in milk and ground beef.
AB  - Real-time PCR has been used previously to detect Yersinia pestis; this study
      applies this rapid, specific, and sensitive nucleic acid-based method to the
      detection and quantitation of Y. pestis specifically in food. Five sets of
      primers and corresponding TaqMan dual-labelled fluorogenic hybridization probes
      for Y. pestis were designed and optimized for specificity testing using genomic
      DNA from 71 bacterial strains. Four Y. pestis -specific primer and probe sets
      were developed, based on the virulence plasmid targets, and used to distinguish
      this bacterium from the various Yersinia and other bacterial species tested. An
      additional primer and probe set, based on a chromosomal gene target,
      distinguished Y. pestis and Yersinia pseudotuberculosis from the various Yersinia
      and other bacterial species tested. With optimized conditions, the quantitative
      detection limit of the probes for Y. pestis pure cultures ranged from 13 to 220
      CFU. Standard curves were generated for the probes and used to determine the
      amplification efficiencies. The primers and probes demonstrated high
      amplification efficiencies, and their performance was evaluated using spiked milk
      and ground beef samples. The quantitative detection limit was 10(1) to 10(3)
      CFU/ml in milk and 10(2) to 10(5) CFU/g in ground beef without any preenrichment
      step. Testing the hybridization probes on food samples demonstrated the detection
      of Y. pestis in a foodborne application; this is the first such report, to our
      knowledge.

PMID- 20051200
TI  - Relationships between processing delay and microbial load of broiler neck skin
      samples.
AB  - The measurable microbial load on poultry carcasses during processing is
      determined by a number of factors including farm or origin, processing hygiene,
      and external temperature. This study investigated associations between carcass
      microbial load and progressive delays to processing. A total of 30 carcasses were
      delayed immediately after defeathering and before evisceration in a commercial
      abattoir in groups of five, and were held at ambient temperature for 1, 2, 3, 4,
      6, and 8 h. Delayed carcasses were reintroduced to the processing line, and
      quantitative assessment of total viable count, coliforms, Staphylococcus aureus,
      and Pseudomonas spp. was undertaken on neck skin flap samples collected after
      carcass chilling and then pooled for each group. Sampling was repeated on 5
      separate days, and the data were combined. Significant increases in total viable
      count (P = 0.001) and coliforms (P = 0.004), but not for S. aureus or Pseudomonas
      loads, were observed across the 8-h period of delay. In line with previous
      studies, there was significant variation in microbiological data according to
      sampling day. In conclusion, there is a significant and measurable decline in
      microbiological status of uneviscerated but defeathered poultry carcasses after
      an 8-h delay, but the variability of sampling results, reflecting the wide range
      of factors that impact microbial load, means that it is not possible to determine
      maximum or minimum acceptable periods of processing delay based on this criterion
      alone.

PMID- 20051201
TI  - Bacteriophage significantly reduces Listeria monocytogenes on raw salmon fillet
      tissue.
AB  - We have demonstrated the antilisterial activity of generally recognized as safe
      (GRAS) bacteriophage LISTEX P100 (phage P100) on the surface of raw salmon fillet
      tissue against Listeria monocytogenes serotypes 1/2a and 4b. In a broth model
      system, phage P100 completely inhibited L. monocytogenes growth at 4 degrees
      Celsius for 12 days, at 10 degrees Celsius for 8 days, and at 30 degrees Celsius
      for 4 days, at all three phage concentrations of 10(4), 10(6), and 10(8) PFU/ml.
      On raw salmon fillet tissue, a higher phage concentration of 10(8) PFU/g was
      required to yield 1.8-, 2.5-, and 3.5-log CFU/g reductions of L. monocytogenes
      from its initial loads of 2, 3, and 4.5 log CFU/g at 4 or 22 degrees Celsius.
      Over the 10 days of storage at 4 degrees Celsius, L. monocytogenes growth was
      inhibited by phage P100 on the raw salmon fillet tissue to as low as 0.3 log
      CFU/g versus normal growth of 2.6 log CFU/g in the absence of phage. Phage P100
      remained stable on the raw salmon fillet tissue over a 10-day storage period,
      with only a marginal loss of 0.6 log PFU/g from an initial phage treatment of 8
      log PFU/g. These findings illustrate that the GRAS bacteriophage LISTEX P100 is
      listericidal on raw salmon fillets and is useful in quantitatively reducing L.
      monocytogenes.

PMID- 20051202
TI  - Increased inactivation of exopolysaccharide-producing Pediococcus parvulus in
      apple juice by combined treatment with enterocin AS-48 and high-intensity pulsed
      electric field.
AB  - The cyclic peptide bacteriocin enterocin AS-48 was tested (at final
      concentrations of 0.175, 0.613, and 1.05 AU/ml) against the exopolysaccharide
      producing cider spoilage strain Pediococcus parvulus 48 in apple juice in
      combination with high-intensity pulsed electric field (HIPEF) treatment (35 kV/cm
      and 150 Hz for 4 mus and bipolar mode). The effect of the combined treatments was
      studied by surface response methodology, with AS-48 concentration and HIPEF
      treatment time as process variables. A bacteriocin concentration of 0.613 AU/ml
      in combination with HIPEF treatment time of 1,000 micros reduced the population
      of pediococci by 6.6 log cycles in apple juice and yielded an apple juice that
      was free from pediococci during a 30-day storage period at 4 and 22 degrees
      Celsius. In contrast, application of HIPEF treatment alone had no effect on the
      surviving pediococci during storage of juice at 22 degrees Celsius. The combined
      treatment significantly improved the stability of the juice against spoilage by
      exopolysaccharide-producing P. parvulus.

PMID- 20051203
TI  - Production, characterization, and antimicrobial activity of a bacteriocin from
      newly isolated Enterococcus faecium IJ-31.
AB  - This work aimed to isolate and characterize Enterococcus spp. from indigenous
      dairy products in Islamabad, Pakistan. By classical microbiological techniques,
      one strain from a butter sample was identified to be Enterococcus faecium, and we
      designated it E. faecium IJ-31. The precise identity of this strain was then
      established by determining the sequence of its 16S and 23S rRNA genes. The
      sequence homology searches revealed matches with a number of previously reported
      strains, such as E. faecium HN-N3 and HN-N29, both isolated from swine intestines
      in China. The newly isolated strain was tested for hemolysis and antibiotic
      sensitivity; it was nonhemolytic on sheep and human blood and sensitive to
      vancomycin. Consistent with its vancomycin sensitivity, repeated attempts to
      amplify the vancomycin resistance genes vanA and vanB failed. Similar attempts to
      amplify the virulence genes gelE, agg, and cyl also failed, suggesting the
      absence of these genes. In contrast, the enterocin-P gene, entP, readily
      amplified with primers based on the previously reported sequences, and the
      deduced sequence showed near identity with a number of reported sequences from E.
      faecium. Further, the 71-residue enterocin-P sequence from strain IJ-31 is only
      the second complete sequence reported. The enterocin was partially purified and
      tested for antibacterial activity. It showed potent inhibitory activity against
      many bacteria, including Listeria monocytogenes, a routinely used test strain.
      Further, the enterocin showed potent activity against Bacillus subtilis and
      Bacillus cereus. The enterocin retained antibacterial activity even following
      heating to 121 degrees Celsius for 15 min. Further, it also retained activity
      after exposure to pH values ranging from 4 to 10. However, proteinase K treatment
      rendered the peptide nonfunctional.

PMID- 20051204
TI  - High-pressure treatment for shelf-life extension and quality improvement of
      oysters cooked in a traditional Taiwanese oyster omelet.
AB  - Whole oysters were processed using high-pressure (HP) treatment at 250 and 300
      MPa for 0 to 10 min and stored at 4 degrees Celsius for up to 28 days. HP-treated
      oysters and untreated oysters were evaluated for lipid oxidation, growth of
      microorganisms, and sensory characteristics after cooking at 160 degrees Celsius
      for 90 s. Microbial counts after HP treatment revealed that the bacterial load
      was initially reduced at all pressures. HP-treated oysters had significantly
      higher pH and moisture (P < 0.05) relative to control (untreated) oysters during
      storage. HP treatment increased lipid oxidation with unpleasant odor during
      storage compared with the control. HP treatment decreased redness but did not
      significantly affect the brightness and yellowness of cooked oysters. From tests
      of mechanical properties, 300 MPa-treated oysters after cooking had significantly
      increased toughness as measured by cutting force. HP-treated oysters after
      cooking received higher quality scores than did the control during the storage
      trial. Results indicated that 300 MPa for 2 min is the optimum HP treatment that
      results in oysters most acceptable for oyster omelets during storage at 4 degrees
      Celsius, and this treatment may extend the shelf life of these oysters to 21
      days.

PMID- 20051205
TI  - Antigenicity and viability of Anisakis larvae infesting hake heated at different
      time-temperature conditions.
AB  - Heat treatments (40 to 94 degrees Celsius, 30 s to 60 min) were applied to
      different batches of Anisakis simplex L3 larvae isolated from hake ovaries and
      viscera to study the effect of heat on the viability of the larvae measured as
      mobility, emission of fluorescence under UV light, and changes in color after
      staining with specific dyes, and on A. simplex antigenic proteins. The aim was to
      determine the lowest time-temperature conditions needed to kill the larvae to
      avoid anisakiasis in consumers, and to evaluate whether high temperature modifies
      the antigenicity of A. simplex extracts. Heating at 60 degrees Celsius for 10 min
      (recommended by some authors) was considered unsafe, as differences in viability
      between batches were found, with some larvae presenting spontaneous movements in
      one batch. At higher temperatures (> or = 70 degrees Celsius for > or = 1 min),
      no movement of the larvae was observed. Antigenic protein Ani s 4 and A. simplex
      crude antigens were detected in the larvae heated at 94 + or - 1 degrees Celsius
      for 3 min. This indicates that allergic symptoms could be provoked in previously
      sensitized consumers, even if the larvae were killed by heat treatment.

PMID- 20051206
TI  - Reduction of patulin in apple cider by UV radiation.
AB  - The presence of the mycotoxin patulin in processed apple juice and cider presents
      a continual challenge to the food industry as both consumer health and product
      quality issues. Although several methods for control and/or elimination of
      patulin have been proposed, no unifying method has been commercially successful
      for reducing patulin burdens while maintaining product quality. In the present
      study, exposure to germicidal UV radiation was evaluated as a possible
      commercially viable alternative for the reduction and possible elimination of the
      patulin mycotoxin in fresh apple cider. UV exposure of 14.2 to 99.4 mJ/cm(2)
      resulted in a significant and nearly linear decrease in patulin levels while
      producing no quantifiable changes in the chemical composition (i.e., pH, Brix,
      and total acids) or organoleptic properties of the cider. For the range of UV
      doses tested, patulin levels decreased by 9.4 to 43.4%; the greatest reduction
      was achieved after less than 15 s of UV exposure. The method of UV radiation (the
      CiderSure 3500 system) is an easily implemented, high-throughput, and cost
      effective method that offers simultaneous UV pasteurization of cider and juice
      products and reduction and/or elimination of patulin without unwanted alterations
      in the final product.

PMID- 20051207
TI  - Drug residues recovered in feed after various feedlot mixer truck cleanout
      procedures.
AB  - A study was conducted to determine the effectiveness of two methods of equipment
      cleanout, sequencing or flushing, for reducing drug carryover in feedlot mixer
      trucks. Feed samples were collected from total mixed rations before and after
      various feed mixer equipment cleanout procedures. Medicated rations contained
      either 11 ppm of tylosin or 166 or 331 ppm of chlortetracycline. There were no
      differences between sequencing and flushing or between flushing with dry barley
      and flushing with barley silage in the median proportion of drug recovered in the
      next ration. A larger drug reduction was achieved using flush material at a
      volume of 10 versus 5% of the mixer capacity and mixing the flush material for 3
      versus 4 min. Regardless of the drug or prescription concentrations in the total
      mixed rations or the equipment cleanout procedure used, concentrations of
      chlortetracycline and tylosin recovered were very low.

PMID- 20051208
TI  - Microbiological sampling of carcasses by excision or swabbing with three types of
      sponge or gauze.
AB  - Fifty-five bovine, 50 equine, 60 ovine, and 50 porcine carcasses were sampled in
      a slaughterhouse in eastern Spain. Two samples were taken from each carcass, one
      using the excision method and the other using the swabbing method. Four different
      materials were used for swabbing: cellulose, polyurethane, or viscose sponges,
      and medical gauze. Samples were collected at the end of the process by four
      different people before the carcasses were taken to the cooler. The samples were
      examined for total viable bacteria counts (TVCs) and Enterobacteriaceae counts
      (ECs). The mean TVC for all species sampled by excision was 4.50 log CFU/cm(2),
      which was significantly higher than the 3.53 log CFU/cm(2) obtained by swabbing.
      The TVCs obtained using gauze and the cellulose and polyurethane sponges were
      significantly higher (P < 0.05) than the corresponding TVCs obtained using
      viscose sponges. Animal species, the person who collected the samples, and
      microbiological load also had a significant effect on TVC. ECs were obtained from
      82.8% of excision samples, from larger percentages of samples obtained using
      cellulose or polyurethane sponges or gauze swabs, but from smaller percentages of
      samples obtained using viscose sponges. The Enterobacteriaceae load significantly
      influenced the EC. In contrast, animal species and the person who collected the
      samples had no significant effect. The cellulose sponge, polyurethane sponge, and
      gauze gave high mean log counts of aerobic bacteria and Enterobacteriaceae, which
      makes these swab types suitable for use in slaughterhouses for the purpose of
      assessing production process hygiene.

PMID- 20051209
TI  - Characteristics of shiga toxin-producing Escherichia coli isolated from Swiss raw
      milk cheese within a 3-year monitoring program.
AB  - Food is an important vehicle for transmission of Shiga toxin-producing
      Escherichia coli (STEC). To assess the potential public health impact of STEC in
      Swiss raw milk cheese produced from cow's, goat's, and ewe's milk, 1,422 samples
      from semihard or hard cheese and 80 samples from soft cheese were examined for
      STEC, and isolated strains were further characterized. By PCR, STEC was detected
      after enrichment in 5.7% of the 1,502 raw milk cheese samples collected at the
      producer level. STEC-positive samples comprised 76 semihard, 8 soft, and 1 hard
      cheese. By colony hybridization, 29 STEC strains were isolated from 24 semihard
      and 5 soft cheeses. Thirteen of the 24 strains typeable with O antisera belonged
      to the serogroups O2, O22, and O91. More than half (58.6%) of the 29 strains
      belonged to O:H serotypes previously isolated from humans, and STEC O22:H8,
      O91:H10, O91:H21, and O174:H21 have also been identified as agents of hemolytic
      uremic syndrome. Typing of Shiga toxin genes showed that stx(1) was only found in
      2 strains, whereas 27 strains carried genes encoding for the Stx(2) group, mainly
      stx(2) and stx(2vh-a/b). Production of Stx(2) and Stx(2vh-a/b) subtypes might be
      an indicator for a severe outcome in patients. Nine strains harbored hlyA
      (enterohemorrhagic E. coli hemolysin), whereas none tested positive for eae
      (intimin). Consequently, semihard and hard raw milk cheese may be a potential
      source of STEC, and a notable proportion of the isolated non-O157 STEC strains
      belonged to serotypes or harbored Shiga toxin gene variants associated with human
      infections.

PMID- 20051210
TI  - Effect of alpha-cyclodextrin-cinnamic acid inclusion complexes on populations of
      Escherichia coli O157:H7 and Salmonella enterica in fruit juices.
AB  - Cinnamic acid (CA), a naturally occurring organic acid found in fruits and
      spices, has antimicrobial activity against spoilage and pathogenic bacteria, but
      low aqueous solubility limits its use. The purpose of this study was to determine
      the effectiveness of solubility-enhancing alpha-cyclodextrin-CA inclusion
      complexes against Escherichia coli O157:H7 and Salmonella enterica serovars
      suspended in apple cider or orange juice at two different incubation temperatures
      (4 and 26 degrees Celsius). Two concentrations (400 and 1,000 mg/liter) of alpha
      cyclodextrin-CA inclusion complex were aseptically added to apple cider
      inoculated with E. coli O157:H7 (7 log CFU/ml) and orange juice inoculated with a
      cocktail of six Salmonella enterica serovars (7 log CFU/ml). Samples were
      extracted at 0 min, at 2 min, and at 24-h intervals for 7 days, serially diluted
      in 0.1 % peptone, spread plated in duplicate onto tryptic soy agar, and incubated
      at 35 degrees Celsius for 24 h. Populations of E. coli O157:H7 in apple cider
      were significantly reduced (P < or = 0.05) during the 7-day sampling period in
      all solutions regardless of temperature. Compared with the controls, populations
      were significantly reduced by the addition of 400 and 1,000 mg/liter inclusion
      complex, but reductions were not significantly different (P > or = 0.05) between
      the two treatment groups (400 and 1,000 mg/liter). Salmonella was significantly
      reduced in all solutions regardless of temperature. There were significant
      differences between the control and each inclusion complex concentration at 4 and
      26 degrees Celsius. Coupled with additional processing steps, alpha-cyclodextrin
      CA inclusion complexes may provide an alternative to traditional heat processes.

PMID- 20051211
TI  - Molecular screening, isolation, and characterization of enterohemorrhagic
      Escherichia coli O157:H7 from retail shrimp.
AB  - Foodborne outbreaks attributed to the contamination of foods with
      enterohemorrhagic Escherichia coli (EHEC) O157:H7 are a growing global concern.
      Fish and shrimp samples obtained from different retail fish markets in Cochin,
      India, were screened by direct PCR assays targeting three important virulence
      markers of EHEC, the intimin protein (eaeA gene), enterohemolysin (hlyA gene),
      and Shiga toxin (stx gene). One shrimp (Fenneropenaeus indicus) sample was
      positive for all these virulence markers, and seven typical E. coli O157:H7
      isolates were recovered from the marker-positive shrimp sample. This is the first
      report of recovery of typical E. coli O157:H7 from fish or shellfish in India.
      All the typical EHEC isolates had a characteristic reaction in eosin methylene
      blue agar and belonged to IMViC (indole, methyl red, Voges Proskauer, Simmons
      citrate reactions) biotype I. These isolates also were negative for sorbitol and
      methylumbelliferyl-beta-glucuronide and exhibited beta-hemolytic activity. One
      isolate showed self-agglutination for E. coli O157 antisera and produced a false
      positive reaction with CHROMagar O157. These typical EHEC isolates belonged to a
      restricted biotype group and had a very low multiple antibiotic resistance index.
      Isolation of E. coli O157:H7 in fish and shellfish indicates that strict
      adherence to hygienic handling methods and proper cooking or processing is needed
      before consumption of these products.

PMID- 20051212
TI  - Rapid estimation of microbial populations in fish samples by using terminal
      restriction fragment length polymorphism analysis of 16S rDNA.
AB  - A rapid system using terminal restriction fragment length polymorphism (T-RFLP)
      analysis targeting 16S rDNA is described for microbial population analysis in
      edible fish samples. The defined terminal restriction fragment database was
      constructed by collecting 102 strains of bacteria representing 53 genera that are
      associated with fish. Digestion of these 102 strains with two restriction
      enzymes, HhaI and MspI, formed 54 pattern groups with discrimination to the genus
      level. This T-RFLP system produced results comparable to those from a culture
      based method in six natural fish samples with a qualitative correspondence of
      71.4 to 92.3%. Using the T-RFLP system allowed an estimation of the microbial
      population within 7 h. Rapid assay of the microbial population is advantageous
      for food manufacturers and testing laboratories; moreover, the strategy presented
      here allows adaptation to specific testing applications.

PMID- 20051213
TI  - Development of biogenic amines during the ripening of Italian dry sausages.
AB  - The effect of modification of different chemical and microbiological parameters
      and the production of biogenic amines (histamine, cadaverine, putrescine, and
      tyramine) was examined during ripening of various types of typical Italian dry
      sausages (salami). Water activity decreased from 0.97 to 0.87, and pH reached the
      lowest value between the 13th and the 20th day of the ripening period, and then
      increased. Putrescine (up to 122.7 mg/kg) and tyramine (up to 105.9 mg/kg) mean
      levels showed dominance in comparison with cadaverine (up to 26.1 mg/kg) and
      histamine (up to 6.2 mg/kg) mean values in all sausage types. The highest
      putrescine and tyramine concentrations were observed in salami with the largest
      diameters. This comparative study suggests a good correlation between microbial
      behavior and amine evolution, particularly tyramine and putrescine, in dry
      sausage production.

PMID- 20051214
TI  - Detection of prohibited animal products in livestock feeds by single-strand
      conformation polymorphism analysis.
AB  - Single-strand conformation polymorphism (SSCP) analysis of amplicons produced
      from a mitochondrial DNA region between the tRNA(Lys) and ATPase8 genes was
      applied for the detection of animal product within livestock feeds.
      Identification of prohibited animal (cattle, elk, sheep, deer, and goat) and
      nonprohibited animal (pig and horse) products from North America was possible
      based on the differential display of the single-stranded DNA fragments for the
      different animal species on SSCP gels. This method allowed specific detection and
      identification of mixed genomic DNA from different animal species. Trace amounts
      of cattle-derived materials were also detected in pig meat and bone meal and in
      grain-based feeds fortified with 10, 5, 1, or 0% porcine meat and bone meal. This
      study demonstrates the applicability of SSCP analyses to successfully identify
      the origin of animal species derived materials potentially present in animal
      feeds.

PMID- 20051215
TI  - Utility of clinical-epidemiological profiles in outbreaks of foodborne disease,
      Catalonia, 2002 through 2006.
AB  - The objective of this study was to evaluate the use of clinical-epidemiological
      profiles for classifying non-laboratory-confirmed outbreaks of foodborne disease
      (FBD) in Catalonia between 2002 and 2006 and for elucidating associations among
      factors contributing to these outbreaks. A total of 275 nonfamily outbreaks were
      studied, of which 190 (69.1%) were laboratory confirmed and 85 (30.9%) were not.
      In 176 (92.6%) of laboratory-confirmed outbreaks and 69 (81.2%) of non-laboratory
      confirmed outbreaks, information was obtained on contributing factors (P =
      0.009). In 72% of non-laboratory-confirmed outbreaks, the etiology was assigned
      by using clinical-epidemiological profiles; thus, 93% of outbreaks eventually
      were associated with an etiology. In laboratory-confirmed outbreaks, poor
      personal hygiene was positively associated with norovirus (odds ratio [OR], 2.69;
      95% confidence interval [CI], 1.47 to 4.89; P = 0.0007) and negatively associated
      with Salmonella and Campylobacter (OR, 0.54; 95% CI, 0.33 to 0.89; P = 0.01), and
      an unsafe source was positively associated with Salmonella and Campylobacter (OR,
      4.07; 95% CI, 1.72 to 10.09; P = 0.001) and negatively associated with norovirus
      (OR, 0.14; 95% CI, 0.04 to 0.58; P = 0.001). No differences were found among
      contributing factors associated with outbreaks with a laboratory-confirmed
      etiology and those associated with outbreaks with an etiology assigned according
      to the clinical-epidemiological profiles. Clinical-epidemiological profiles are
      useful for determining what prevention and control strategies are appropriate to
      the agents involved in each community and for designing outbreak investigations.

PMID- 20051217
TI  - Parameters for determining inoculated pack/challenge study protocols.
AB  - The National Advisory Committee on Microbiological Criteria for Foods developed
      guidelines for conducting challenge studies on pathogen inhibition and
      inactivation studies in a variety of foods. The document is intended for use by
      the food industry, including food processors, food service operators, and food
      retailers; federal, state, and local food safety regulators; public health
      officials; food testing laboratories; and process authorities. The document is
      focused on and limited to bacterial inactivation and growth inhibition and does
      not make specific recommendations with respect to public health. The Committee
      concluded that challenge studies should be designed considering the most current
      advances in methodologies, current thinking on pathogens of concern, and an
      understanding of the product preparation, variability, and storage conditions.
      Studies should be completed and evaluated under the guidance of an expert
      microbiologist in a qualified laboratory and should include appropriate
      statistical design and data analyses. This document provides guidelines for
      choice of microorganisms for studies, inoculum preparation, inoculum level,
      methods of inoculation, incubation temperatures and times, sampling
      considerations, and interpreting test results. Examples of appropriately designed
      growth inhibition and inactivation studies are provided.

PMID- 20051216
TI  - The REFLECT statement: methods and processes of creating reporting guidelines for
      randomized controlled trials for livestock and food safety.
AB  - The conduct of randomized controlled trials in livestock with production, health,
      and food-safety outcomes presents unique challenges that may not be adequately
      reported in trial reports. The objective of this project was to modify the
      CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the
      unique aspects of reporting these livestock trials. A two-day consensus meeting
      was held on November 18-19, 2008 in Chicago, Ill, United States of America, to
      achieve the objective. Prior to the meeting, a Web-based survey was conducted to
      identify issues for discussion. The 24 attendees were biostatisticians,
      epidemiologists, food-safety researchers, livestock production specialists,
      journal editors, assistant editors, and associate editors. Prior to the meeting,
      the attendees completed a Web-based survey indicating which CONSORT statement
      items may need to be modified to address unique issues for livestock trials. The
      consensus meeting resulted in the production of the REFLECT (Reporting Guidelines
      for Randomized Control Trials) statement for livestock and food safety (LFS) and
      22-item checklist. Fourteen items were modified from the CONSORT checklist, and
      an additional sub-item was proposed to address challenge trials. The REFLECT
      statement proposes new terminology, more consistent with common usage in
      livestock production, to describe study subjects. Evidence was not always
      available to support modification to or inclusion of an item. The use of the
      REFLECT statement, which addresses issues unique to livestock trials, should
      improve the quality of reporting and design for trials reporting production,
      health, and food-safety outcomes.

PMID- 20051218
TI  - Influence of anesthetic drugs and concurrent psychiatric medication on seizure
      adequacy during electroconvulsive therapy.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is performed under anesthesia and
      muscle relaxation. Only well-generalized seizures seem to have the high
      "adequacy" or "quality" that have been claimed to reflect positive predictive
      power for the outcome of an ECT course. The induction of well-generalized
      seizures can be potentially influenced by several variables. One major variable
      is concurrent medication including anesthetic drugs, since most anesthetic drugs
      are potent anticonvulsives. We hypothesized a negative influence of anesthetics
      and benzodiazepines but a positive effect of antidepressants and antipsychotics
      concurrently applied during ECT on seizure adequacy. METHOD: We included
      inpatients (n = 41) with a DSM-IV-diagnosed major depressive episode treated with
      ECT (411 ECT sessions) during a period of 20 months (May 2005 to December 2006)
      in an open label and noncontrolled study. A repeated measurement regression
      analysis was performed with 8 seizure adequacy parameters as dependent variables.
      We indirectly quantified narcotic agent influence with bispectral index
      monitoring. RESULTS: In contrast to the impact of psychiatric comedication, this
      measure of "depth of narcosis" prior stimulation turned out to influence most
      seizure adequacy parameters in a highly significant manner. CONCLUSIONS: Thus, we
      concluded that the anticonvulsive properties of narcotic agents have much higher
      influence than concomitant psychotropic medication. Our data support the view
      that a significant influence of concurrent psychotropic drugs on seizure adequacy
      markers is missing, especially when directly compared with other confounders like
      stimulation energy, age, and depth of narcosis. The latter suggests to further
      prove the idea that lighter anesthesia is indeed an important tool to get
      patients faster into remission.

PMID- 20051219
TI  - Noninvasive brain stimulation with high-frequency and low-intensity repetitive
      transcranial magnetic stimulation treatment for posttraumatic stress disorder.
AB  - OBJECTIVE: We aimed to investigate the efficacy of 20 Hz repetitive transcranial
      magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal
      cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress
      disorder (PTSD)-associated symptoms. METHOD: In this double-blind, placebo
      controlled phase II trial conducted between October 2005 and July 2008, 30
      patients with DSM-IV-diagnosed PTSD were randomly assigned to receive 1 of the
      following treatments: active 20 Hz rTMS of the right DLPFC, active 20 Hz rTMS of
      the left DLPFC, or sham rTMS. Treatments were administered in 10 daily sessions
      over 2 weeks. A blinded rater assessed severity of core PTSD symptoms,
      depression, and anxiety before, during, and after completion of the treatment
      protocol. In addition, a battery of neuropsychological tests was measured before
      and after treatment. RESULTS: Results show that both active conditions-20 Hz rTMS
      of left and right DLPFC-induced a significant decrease in PTSD symptoms as
      indexed by the PTSD Checklist and Treatment Outcome PTSD Scale; however, right
      rTMS induced a larger effect as compared to left rTMS. In addition, there was a
      significant improvement of mood after left rTMS and a significant reduction of
      anxiety following right rTMS. Improvements in PTSD symptoms were long lasting;
      effects were still significant at the 3-month follow-up. Finally,
      neuropsychological evaluation showed that active 20 Hz rTMS is not associated
      with cognitive worsening and is safe for use in patients with PTSD. CONCLUSIONS:
      These results support the notion that modulation of prefrontal cortex can
      alleviate the core symptoms of PTSD and suggest that high-frequency rTMS of right
      DLPFC might be the optimal treatment strategy.

PMID- 20051220
TI  - A comparison of the efficacy of medications for adult attention
      deficit/hyperactivity disorder using meta-analysis of effect sizes.
AB  - OBJECTIVES: Medications used to treat attention-deficit/hyperactivity disorder
      (ADHD) in adults have been well researched, but comparisons among drugs are
      hindered by the absence of direct comparative trials. Our objectives were to (1)
      estimate the effect size of the medications used to treat adult ADHD, (2)
      determine if differences in the designs of studies confound comparisons of
      medication efficacy, (3) quantify the evidence for differences in effect sizes
      among medications, and (4) see if features of study design influence estimates of
      efficacy. DATA SOURCES: The following search engines were used: PubMed, Ovid,
      ERIC, CINAHL, MEDLINE, PREMEDLINE, the Cochrane database, e-psyche, and Social
      Sciences Abstracts. Presentations from the American Psychiatric Association and
      American Academy of Child and Adolescent Psychiatry meetings were reviewed. STUDY
      SELECTION: A literature search was conducted to identify double-blind, placebo
      controlled studies of ADHD in adults published in English after 1979. Only trials
      that used DSM-III, -III-R, or -IV ADHD criteria and followed subjects for > or =
      2 weeks were selected. DATA EXTRACTION: Meta-analysis regression assessed the
      influence of medication type and study design features on medication effects.
      RESULTS: Nineteen trials met criteria and were included in this meta-analysis.
      These trials studied 13 drugs using 18 different outcome measures of hyperactive,
      inattentive, or impulsive behavior. After trials were stratified on the class of
      drug studied (short-acting stimulant vs long-acting stimulant vs nonstimulant),
      significant differences in effect size were observed between stimulant and
      nonstimulant medications (P = .006 and P = .0001, respectively, for short- and
      long-acting stimulants vs nonstimulants), but the effect for short-acting
      stimulants was not significant after correcting for study design features. The
      effect sizes for each drug class were similar in magnitude to what we previously
      reported for medication treatment studies of children with ADHD. We found
      significant heterogeneity of effect sizes for short-acting stimulants (P < .001)
      but not for other medication groups. CONCLUSIONS: Although both stimulant and
      nonstimulant medications are effective for treating ADHD in adults, stimulant
      medications show greater efficacy for the short durations of treatment
      characteristic of placebo-controlled studies. We found no significant differences
      between short- and long-acting stimulant medications. Study design features vary
      widely among studies and can confound indirect comparisons unless addressed
      statistically as we have done in this study.

PMID- 20051221
TI  - A double-blind, placebo-controlled study of armodafinil for excessive sleepiness
      in patients with treated obstructive sleep apnea and comorbid depression.
AB  - OBJECTIVE: Treatment of excessive sleepiness in the context of obstructive sleep
      apnea (OSA) may be particularly difficult in those with depression because
      depression and/or antidepressant medications may cause sleepiness and fatigue in
      addition to that due to the OSA. This study evaluating armodafinil, a
      nonamphetamine wakefulness-promoting medication, is the first trial for treatment
      of excessive sleepiness in patients with treated OSA and comorbid depression.
      METHOD: Men and women with OSA diagnosed using International Classification of
      Sleep Disorders criteria being treated with continuous positive airway pressure
      and comorbid major depressive disorder or dysthymic disorder according to DSM-IV
      TR criteria were enrolled into a 12-week, randomized, double-blind, parallel
      group study between September 2007 and March 2009 at 60 outpatient sites.
      Patients maintained on stable monotherapy with a serotonergic antidepressant and
      with a 17-item Hamilton Depression Rating Scale score < 17 received placebo or
      armodafinil (target dose: 200 mg once daily). Coprimary outcomes were the
      proportion of patients with at least minimal improvement on the Clinical Global
      Impression of Change (CGI-C) as related to excessive sleepiness and mean change
      from baseline in Maintenance of Wakefulness Test mean sleep latency at final
      visit; the key secondary outcome was mean change in the Epworth Sleepiness Scale
      score. RESULTS: 249 patients were enrolled: 125 in the armodafinil group and 124
      in the placebo group. The proportion of patients with at least minimal
      improvement on the CGI-C was statistically significantly greater in the
      armodafinil group (69%) compared with the placebo group (53%, P = .012). Mean
      (SD) increase in Maintenance of Wakefulness Test sleep latency was numerically
      but not significantly greater following armodafinil (2.6 [7.1] min) versus
      placebo (1.1 [7.6] min, P = .30) treatment. Mean decrease in Epworth Sleepiness
      Scale score was greater in the armodafinil group (-6.3 [4.8]) than in the placebo
      group (-4.8 [4.9], nominal P = .003). Headache, dry mouth, and insomnia were the
      most common adverse events occurring with armodafinil treatment. There was no
      clinically significant effect on depression in either group as measured by the
      Quick Inventory of Depressive Symptomatology-Self-Report 16. CONCLUSIONS:
      Armodafinil significantly improved overall clinical condition related to
      excessive sleepiness as rated by the CGI-C and was well tolerated in patients
      with treated OSA and comorbid depression. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00518986.

PMID- 20051222
TI  - A mammalian reporter system for fast and quantitative detection of intracellular
      A-to-I RNA editing levels.
AB  - An important molecular mechanism to create protein diversity from a limited set
      of genes is A-to-I RNA editing. RNA editing converts single adenosines into
      inosines in pre-mRNA. These single base conversions can have a wide variety of
      consequences. Editing can lead to codon changes and, consequently, altered
      protein function. Moreover, editing can alter splice sites and influences miRNA
      biogenesis and target recognition. The two enzymes responsible for editing in
      mammals are adenosine deaminase acting on RNA (ADAR) 1 and 2. However, it is
      currently largely unknown how the activity of these enzymes is regulated in vivo.
      Editing activity does not always correlate with ADAR expression levels,
      suggesting posttranscriptional or posttranslational mechanisms for controlling
      activity. To investigate how editing is regulated in mammalian cells, we have
      developed a straightforward quantitative reporter system to detect editing
      levels. By employing luciferase activity as a readout, we could easily detect
      different levels of editing in a cellular context. In addition, increased levels
      of ADAR2 correlated with increased levels of luciferase activity. This reporter
      system therefore sets the stage for the effective screening of cDNA libraries or
      small molecules for strong modulators of intracellular editing to ultimately
      elucidate how A-to-I editing is regulated in vivo.

PMID- 20051223
TI  - The product of the alternative oxidase is still H2O.

PMID- 20051224
TI  - Unusual oxygen binding behavior of a 24-meric crustacean hemocyanin.
AB  - Hemocyanins from Crustacea usually are found as 1x6 or 2x6-meric assemblies. An
      exception is the hemocyanin isolated from thalassinidean shrimps where the main
      component is a 24-meric structure. Our analysis of oxygen binding data of the
      thalassinidean shrimp Upogebia pusilla based on a three-state MWC-model revealed
      that despite the 24-meric structure the functional properties can be described
      very well based on the hexamer as allosteric unit. In contrast to the hemocyanins
      from other thalassinidean shrimps the oxygen affinity of hemocyanin from U.
      pusilla is increased upon addition of l-lactate. A particular feature of this
      hemocyanin seems to be that l-lactate already enhances oxygen affinity under
      resting conditions which possibly compensates the rather low intrinsic affinity
      observed in absence of l-lactate. The fast rate of oxygen dissociation might
      indicate that in this hemocyanin a higher cooperativity is less important than a
      fast response of saturation level to changes in oxygen concentration.

PMID- 20051226
TI  - Characterization of BNT2, an intrinsically curved DNA of Escherichia coli
      O157:H7.
AB  - The gene regulation by intrinsically curved DNA is one way for bacterial sensing
      of and response to environmental changes. Previously, we showed that the genetic
      element BNT2 upstream of the ecf (eae-positive conserved fragment) operon in the
      Escherichia coli O157:H7 virulence plasmid (pO157) has characteristics typical of
      intrinsically curved DNA, including the presence of multi-homopolymeric
      adenine:thymine tracts (AT tracts) and electrophoretic anomaly at 4 degrees C.
      Here we report that a local intrinsic curvature induced by the two phased AT
      tracts within the unusual promoter sequence of BNT2 played a major role for its
      temperature-dependent promoter activity. The base substitution of the AT tract in
      the spacer DNA between the -35 and the unusual -10 regions of the BNT2 promoter
      with non-AT tract sequence reduced intrinsic curvature slightly at 4 degrees C,
      but greatly affected its transcriptional activity. This implies that such a local
      intrinsic curvature within the unusual promoter of BNT2 is important for
      thermoregulation of the ecf operon.

PMID- 20051227
TI  - Leptin upregulates the expression of plasminogen activator inhibitor-1 in human
      vascular endothelial cells.
AB  - A prothrombotic state in obesity may be partially responsible for the higher
      incidence of atherosclerotic complications. However the factors responsible for
      this prothrombotic state, linked with high levels of plasminogen activator
      inhibitor-1 (PAI-1), are not fully known. Leptin is elevated in obesity and
      studies have shown a positive correlation between leptin and PAI-1 levels in
      human subjects, along with a negative correlation with tissue-type plasminogen
      activator (tPA). We tested the hypothesis that leptin induces PAI-1 and inhibits
      tPA expression using human coronary artery endothelial cells (HCAEC) in culture
      as these cells play an important role in atherosclerosis. We demonstrate that
      leptin induces the transcription and translation of PAI-1 in HCAEC. The leptin
      dependent upregulation of PAI-1 mRNA and protein was comparable to insulin
      induced PAI-1 expression. We show leptin concentration (0-150 ng/ml) dependent
      increases in PAI-1 mRNA and protein after 6 and 12h of leptin administration,
      respectively. Increased intracellular PAI-1 expression correlates with increased
      PAI-1 activity in conditioned media and inhibition of specific ERK1/2 pathway by
      treatment with PD98059 (20-40 microM) inhibits leptin dependent PAI-1 expression.
      However no changes in tPA expression were seen with time or increasing
      concentrations of leptin. Also leptin treatment did not alter total tPA
      concentration or tPA activity in conditioned media. In conclusion, our study
      shows that leptin upregulates the expression of PAI-1 in vascular endothelial
      cells via activation of ERK1/2 but does not regulate tPA expression. These
      studies demonstrate a novel mechanism for the prothrombotic role of leptin in
      development of atherosclerosis.

PMID- 20051228
TI  - CTCF is a DNA methylation-sensitive positive regulator of the INK/ARF locus.
AB  - The INK4B-ARF-INK4A (INK/ARF) locus is composed of three tumor suppressor genes,
      which are kept silenced by DNA methylation in different cancer types. In
      addition, a non-coding RNA (ANRIL) is transcribed in the anti-sense orientation
      upstream of the ARF gene. The resulting divergent promoter region is bound by the
      chromatin insulator protein CTCF in association with histone H3 tri-methylated on
      lysine 4, irrespective of transcription of ANRIL and ARF. Methylation of the
      overlapping CpG island abolishes CTCF binding and the associated modification,
      which can be restored by 5-Aza-2'-deoxycytidine (5-Aza-dC) treatment. shRNA knock
      down of CTCF expression dramatically reduces the induction of ANRIL and ARF, but
      also that of INK4A and INK4B expression by 5-Aza-dC. We propose that CTCF is an
      essential factor for transcription of the INK/ARF locus and that abrogation of
      its binding by DNA methylation contributes to the permanent silencing of several
      genes of the locus in tumors.

PMID- 20051229
TI  - Water deprivation increases angiotensin-converting enzyme but not AT(1) receptor
      expression in brainstem and paraventricular nucleus of the hypothalamus of the
      rat.
AB  - The rostral ventrolateral medulla (RVLM) is critical to the maintenance of blood
      pressure. It has been proposed that blood-borne Ang II can influence the RVLM via
      a neural connection between the circumventricular organs and paraventricular
      nucleus of the hypothalamus (PVH) and that a component of this pathway is
      angiotensinergic. A period of water deprivation leads to increased ability of
      angiotensin type 1 (AT(1)) receptor antagonists to reduce blood pressure when
      administered into the RVLM and PVH. We studied the differences in AT(1) receptor
      and angiotensin-converting enzyme (ACE) expression in these and other brain
      regions involved in blood pressure regulation and water intake following
      dehydration. AT(1) receptor and ACE expression in brains of rats deprived of
      water for 48 h were compared to that of water-replete rats by quantitative
      receptor autoradiography. AT(1) receptor expression was increased in the
      subfornical organ and periventricular nucleus of the hypothalamus, but not in
      other brain regions measured. ACE expression was increased in the RVLM, PVH,
      choroid plexus, median preoptic nucleus, and organosum vasculosum of the lamina
      terminalis. These findings suggest that increased Ang II production but not
      increased receptor expression in the PVH and RVLM is the mechanism by which Ang
      II in the brain helps to sustain systemic blood pressure during periods of water
      deprivation.

PMID- 20051231
TI  - Differences in processing violations of sequential and feature regularities as
      revealed by visual event-related brain potentials.
AB  - Identifying novel or unexpected events which violate predictions based on the
      regularities extracted from our environment is crucially important for adaptive
      behavior. However, the exact dynamics of processing such events is not well
      understood. Furthermore, it is not known in which degree the process of deviant
      detection differs across contexts and how much it depends on the characteristics
      of deviant events. This issue was addressed by the present study which used event
      related potentials (ERPs) in order to investigate the dynamics of identifying two
      types of deviants presented within the same visual setting. These events violated
      expectations based on two different types of information contained within each
      trial, either temporal order of stimulus presentation (sequential deviant) or
      physical attributes shared by the majority of individual stimuli (feature
      deviant). The obtained results indicate a certain degree of similarity in
      detecting two deviant types which, when task-relevant, both elicited N2 and P3b
      event-related potential components. However, significant differences across
      different stages of their processing were also identified. First, only feature,
      but not sequential deviants elicited an N1 enhancement. Furthermore, N2 and P3b
      responses elicited by sequential and feature deviants differed in their latency
      and topography and, in case of P3b, amplitude. Taken together, these results
      suggest that the dynamics of detecting different types of deviants strongly
      depends on the specific characteristics of such events. Furthermore, the
      identified differences in the topography of N2 and P3b indicate distinct
      mechanisms underlying several stages of their processing.

PMID- 20051230
TI  - Changes in regional activity are accompanied with changes in inter-regional
      connectivity during 4 weeks motor learning.
AB  - Structural equation modeling (SEM) and fMRI were used to test whether changes in
      the regional activity are accompanied by changes in the inter-regional
      connectivity as motor practice progresses. Ten healthy subjects were trained to
      perform finger movement task daily for 4 weeks. Three sessions of fMRI images
      were acquired within 4 weeks. The changes in inter-regional connectivity were
      evaluated by measuring the effective connectivity between the primary motor area
      (M1), supplementary motor area (SMA), dorsal premotor cortex (PMd), basal ganglia
      (BG), cerebellum (CB), and posterior ventrolateral prefrontal cortex (pVLPFC).
      The regional activities in M1 and SMA increased from pre-training to week 2 and
      decreased from week 2 to week 4. The inter-regional connectivity generally
      increased in strength (with SEM path coefficients becoming more positive or
      negative) as practice progressed. The increases in the strength of the inter
      regional connectivity may reflect long-term reorganization of the skilled motor
      network. We suggest that the performance gain was achieved by dynamically tuning
      the inter-regional connectivity in the motor network.

PMID- 20051232
TI  - Dissociation of the electrophysiological correlates of familiarity strength and
      item repetition.
AB  - Event-related potentials (ERPs) were employed to investigate the relationship
      between the familiarity strength of recognition memory test items (pictures of
      animate and inanimate objects) and a putative ERP correlate of familiarity, the
      mid-frontal 'old/new' effect. A modified Remember/Know task was used in which
      subjects endorsed items as 'remembered' if any detail of the study presentation
      could be retrieved and, if not, judged the old/new status of the item using a 4
      point confidence scale ('confident old' to 'confident new'). Studied test items
      elicited a mid-frontal old/new effect that varied according to the rated
      familiarity of the eliciting item. Thus, prior findings that the mid-frontal
      effect is graded according to familiarity strength are not attributable to the
      confounding influence of study status, as has been suggested. ERPs elicited by
      studied and unstudied items that were rated equally familiar differed in the same
      latency range as that occupied by the mid-frontal old/new effect. Furthermore,
      the scalp topography of this repetition effect differed significantly from the
      topography of the mid-frontal effect. The findings suggest that ERPs elicited by
      recognition memory test items are modulated during the 300-500 ms latency range
      both by the familiarity strength of the item and, separately, by an implicit
      memory process that acts independently of the processes supporting familiarity
      driven recognition judgments.

PMID- 20051233
TI  - Descending projections to the hindbrain and spinal cord in the paddlefish
      Polyodon spathula.
AB  - In vertebrates, almost all motor neurons innervating skeletal muscles are located
      in the hindbrain and spinal cord, and all brain centers that control behavior
      have descending projections into these parts of the central nervous system. With
      tracer injections into the spinal cord and hindbrain, we have studied cell groups
      with descending projections in the paddlefish. Spinal cord injections reveal
      retrogradely labeled cells in all reticular and raphe nuclei, as well as the
      nucleus of the medial longitudinal fascicle. Additional cell groups with
      projections to the spinal cord are the nucleus of the fasciculus solitarius,
      descending trigeminal nucleus, several octavolateral nuclei, the dorsal
      hypothalamic nucleus, and the pretectum. The only primary sensory fibers with
      descending projections are trigeminal fibers. Hindbrain injections reveal a
      number of additional cell groups in di- and mesencephalon. The most prominent
      source is the mesencephalic tectum. Other descending cells were found in the
      dorsal posterior thalamic nucleus, ventral thalamus, torus semicircularis,
      lateral mesencephalic nucleus, and the central gray of the mesencephalon. Our
      data show that descending spinal projections are comparable to those of other
      vertebrates and that the tectum is the most important motor control center
      projecting to the hindbrain. A surprising result was that the dorsal posterior
      thalamic nucleus also projects to the hindbrain. This nucleus is thought to be a
      center that relays sensory information to the telencephalon. Further studies are
      needed to determine the complete set of projections of the dorsal thalamus in
      paddlefish and other fishes to gain insights into its functional role.

PMID- 20051234
TI  - Preference for a high fat diet, but not hyperphagia following activation of mu
      opioid receptors is blocked in AgRP knockout mice.
AB  - Activation of mu opioid receptors (MOR) makes animals hyperphagic and selectively
      increases their preference for a high fat diet independent of their dietary
      preference. The orexigenic peptide Agouti Related Peptide (AgRP) also produces
      hyperphagia and increased the preference for a high fat diet. In this paper, we
      tested the hypothesis that the effect of MOR on feeding behavior will be
      attenuated in the absence of the orexigenic peptide AgRP. Immunohistochemical
      studies demonstrated that MOR are co-localized on AgRP neurons located in the
      arcuate nucleus. This finding is consistent with a role of MOR in mediating the
      release of AgRP. Our data also demonstrated that the wild-type (FVB) animals
      preferred a diet high in fat whereas the AgRP knockout (AgRP KO) mice did not.
      mRNA expression of MOR in the hypothalamus was not significantly different
      between AgRP KO mice and their wild-type control. In a dose-response experiment,
      the low dose (0.025 microg) of a MOR agonist, DAMGO, increased cumulative food
      intake in wild-type and AgRP KO mice. The low and middle (0.25 microg) dose of
      DAMGO significantly increased the amount of high fat diet eaten by the wild-type
      animals, but did not significantly change the amount of high fat diet eaten by
      the AgRP KO mice. The highest dose of DAMGO (2.5 microg) reduced food intake in
      the control and AgRP KO mice, probably due to somnolence. These data demonstrate
      that the increased preference for a high fat diet after stimulation of MOR is
      attenuated in the absence of AgRP, but the increase in food intake (i.e.
      hyperphagia) is not.

PMID- 20051235
TI  - Misaligning face halves increases and delays the N170 specifically for upright
      faces: implications for the nature of early face representations.
AB  - The N170 is an occipito-temporal visual event-related potential that is larger in
      response to faces than other nonface object categories and has been associated
      with the early activation of visual face representations in the human brain. It
      has been recently showed that spatially misaligning the bottom and top halves of
      a face stimulus-a manipulation used in behavioural studies to disrupt the
      processing of the whole face configuration (i.e. holistic processing)-increases
      the latency and the amplitude of the N170, particularly in the right hemisphere.
      Here we show that these observations cannot be accounted for by a general effect
      of spatial misalignment of visual patterns. A first experiment showed that the
      effect of misalignment on the N170 was larger when both top and bottom halves of
      the stimulus were made of face parts (i.e. a full face) compared to when one of
      the two halves was made of visual noise. The N170 delay and increase for
      misaligned faces is similar to the effect of upside-down face inversion, a
      manipulation thought to disrupt holistic processing. Supporting this view, in a
      second experiment in which we presented upside-down versions of the stimuli used
      in the first experiment, we did not observe such a larger effect of misalignment
      on the N170 for a full face compared to the control conditions. These
      observations support the view that the early face representation activated in the
      human brain at the level of the N170, is that of a global upright face pattern.
      Specifically, when the global configuration of a face is modified by inverting it
      or spatially misaligning its top and bottom halves, the activation of its
      representation is delayed in cortical areas coding preferentially for faces.
      Moreover, when the global face configuration is disrupted, the face stimulus
      appears to recruit additional neural processes compared to normal face
      processing, leading to an increase of the N170 amplitude on the scalp.

PMID- 20051236
TI  - Antinociceptive effects of galanin in the central nucleus of amygdala of rats, an
      involvement of opioid receptors.
AB  - The central nucleus of amygdala (CeA) is a very important brain structure
      involved in multiple physiological functions, especially in pain modulation.
      There are high densities of galanin and galanin receptors found in the CeA. The
      present study was performed to explore the antinociceptive effects of galanin in
      the CeA of rats, and possible involvements of opioid receptors in the galanin
      induced antinociception. Intra-CeA injection of galanin induced dose-dependent
      increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and
      mechanical stimulations in rats. Interestingly, the amtinociceptive effect
      induced by intra-CeA injection of galanin was blocked by intra-CeA injection of
      naloxone, a common opioid receptor antagonist, indicating an involvement of
      opioid receptors in the galanin-induced antinociception in the CeA of rats.
      Moreover, intra-CeA injection of either selective mu-opioid receptor antagonist
      beta-funaltrexamine (beta-FNA) or delta-opioid receptor antagonist naltrindole,
      but not kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI),
      significantly attenuated the galanin-induced increases in HWLs in the CeA of
      rats. Taken together, the results demonstrate that galanin induces
      antinociceptive effects in the CeA of rats, and both mu- and delta-opioid
      receptors are involved in the galanin-induced antinociception.

PMID- 20051237
TI  - Event-related potential correlates of item and source memory strength.
AB  - Event-related potential (ERP) studies of recognition memory have shown
      dissociations between item recognition and source memory, wherein item
      recognition is associated with the mid-frontal FN400 component, which varies
      continuously with item memory strength, while source memory is associated with
      the late parietal effect (LPC). There is current debate about whether source
      memory can vary along a continuum of memory strength or is a threshold process.
      The LPC has been shown to be generally sensitive to correct versus incorrect
      source judgments, but varying levels of "source strength" along a single
      dimension of source evidence have not been tested. The current experiment had
      participants encode novel visual objects in one of two different task contexts by
      performing either a conceptual or perceptual judgment about the object. On a
      subsequent memory test, participants made an old/new decision on a 4-point
      confidence scale followed by a source memory confidence judgment, in which they
      indicated their confidence about which task they had performed with the object at
      encoding. ERPs from the memory test were examined for electrophysiological
      correlates of both item and source memory strength. Item memory was associated
      with differences in the 300-500 ms time window, consistent with the timing of the
      FN400. Differences in the amplitude of the LPC were observed between correct and
      incorrect source decisions, consistent with previous findings. Comparing low and
      high confidence source decisions also revealed differences, suggesting that the
      LPC is also sensitive to variations in the strength of source memory.

PMID- 20051238
TI  - Ubiquitin-positive intranuclear inclusions in neuronal and glial cells in a mouse
      model of the fragile X premutation.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset
      neurodegenerative disorder caused by CGG trinucleotide repeat expansions in the
      fragile X mental retardation 1 (FMR1) gene. The neuropathological hallmark of the
      disease is the presence of ubiquitin-positive intranuclear inclusions in neurons
      and in astrocytes. Ubiquitin-positive intranuclear inclusions have also been
      found in the neurons of transgenic mice model carrying an expanded CGG((98))
      trinucleotide repeat of human origin but have not previously been described in
      glial cells. Therefore, we used immunocytochemical methods to determine the
      pathological features of nuclear and/or cytoplasmic inclusions in astrocytes,
      Bergmann glia, and neurons, as well as relationships between inclusion patterns,
      age, and repeat length in CGG knock-in (KI) mice in comparison with wild-type
      mice. In CGG KI mice, ubiquitin-positive intranuclear inclusions were found in
      neurons (e.g., pyramidal cells, GABAergic neurons) throughout the brain in
      cortical and subcortical brain regions; these inclusions increased in number and
      size with advanced age. Ubiquitin-positive intranuclear inclusions were also
      present in protoplasmic astrocytes, including Bergmann glia in the cerebellum.
      The morphology of intranuclear inclusions in CGG KI mice was compared to that of
      typical inclusions in human neurons and astrocytes in postmortem FXTAS brain
      tissue. This new finding of previously unreported pathology in astrocytes of CGG
      KI mice now provides an important mouse model to study astrocyte pathology in
      human FXTAS.

PMID- 20051239
TI  - Simultaneous interpreters as a model for neuronal adaptation in the domain of
      language processing.
AB  - In the context of language processing, proficiency and age of acquisition have
      reliably been shown to have a strong influence on the functional and structural
      architecture of the human brain. The aim of the present EEG study was to examine
      the impact of language training as experienced by simultaneous interpreters (SI)
      on auditory word processing and to disentangle its influence from that of
      proficiency and age of acquisition. Eleven native German SI and controls matched
      in L2 proficiency and age of acquisition were asked to judge whether auditory
      presented disyllabic noun pairs both within and across the German (L1) and
      English (L2) languages were either semantically congruent or incongruent. We
      revealed enlarged N400 responses in SI while they detected incongruent trials
      both within the native (L1) and non-native (L2) language and also while they
      performed the task in the opposite direction as specifically trained (L1 to L2).
      These enlarged N400 responses in SI suggest a training-induced altered
      sensitivity to semantic processing within and across L1 and L2. The enlarged N400
      responses we revealed in SI to congruent noun pairs during the German-English
      condition (L1 to L2) may indicate that SI could not benefit from an L1 prime when
      the target was a L2 word, suggesting additional processing resulting from long
      term backwards (L2 to L1) training.

PMID- 20051240
TI  - Assessment of different induction protocols to elicit long-term depression (LTD)
      in the rat visual cortex in vivo.
AB  - Changes in synaptic efficacy, including long-term potentiation (LTP) and long
      term depression (LTD), provide mechanisms for experience-induced plasticity of
      cortical and subcortical circuits. LTP is readily induced under drastically
      different experimental conditions (e.g., in vitro and in vivo). However, few
      studies have compared the effectiveness of different induction protocols to
      elicit synaptic depression, especially under in vivo conditions. Here, we
      assessed the effectiveness of four different low frequency stimulation (LFS)
      protocols, applied to the lateral geniculate nucleus, to induce LTD-like changes
      of local field postsynaptic potentials (fPSPs) recorded on the surface of the
      primary visual cortex (V1) of urethane-anesthetized rats. Three LFS protocols
      (900 pulses at 1 Hz; 1800 pulses at 1 Hz, 1800 pulses at 1 Hz, repeated three
      times), known to induce LTD in neocortical and hippocampal slice preparations,
      failed to induce synaptic depression. In contrast, strong low frequency burst
      stimulation (3 pulses/burst at 20 Hz, 900 bursts repeated at 1 Hz) resulted in
      significant, but transient ( approximately 20 min) depression of fPSPs in V1.
      This effect was resistant to systemic treatment with MK 801 (0.5 mg/kg) or local,
      cortical application of either APV (10 mM) or MCPG (10 mM), indicative of non
      essential roles of N-methyl-d-aspartate and metabotropic glutamate receptors. A
      similar depressant effect was also observed under sodium pentobarbital
      anesthesia. These experiments emphasize the resistance of the in vivo neocortex
      to express the long-lasting down-regulation of synaptic strength, observations
      that require integration into current models and theories regarding the functions
      of LTD as a homeostatic and experience-dependent plasticity mechanism.

PMID- 20051241
TI  - Mechanical contributions to astrocyte adhesion using a novel in vitro model of
      catheter obstruction.
AB  - Drainage and diversion of cerebrospinal fluid (CSF) through shunt systems is the
      most common treatment for hydrocephalus, but complications due to tissue
      obstruction of the catheter occur in up to 61% of patients. Although shunt
      systems have undergone limited technological advancements to resist mammalian
      cell adhesion, there is a need to further reduce adhesion that can exacerbate
      obstruction. The high intrinsic variability in clinical studies and an inability
      to predict chronic adhesion of host cells in vitro while maintaining the
      environmental conditions observed in hydrocephalus have impeded progress. We
      designed the hydrocephalus shunt catheter bioreactor (HSCB) to measure
      inflammatory cell adhesion under experimentally manipulated conditions of CSF
      pressure, pulsation rate, and flow rates. For a 20-h period, astrocytes were
      perfused through the pulsatile flow system, and adhesion on silicone catheters
      was recorded. These results were compared with those obtained under static cell
      culture conditions. Astrocyte adhesion was significantly increased under
      conditions of increased flow rate (0.25 and 0.30 mL/min), and a trend toward
      increased adhesion was observed under conditions of elevated pressure and
      pulsation rate. Because the HSCB represents physiologic conditions more
      accurately than static cell culture, our results suggest that standard static
      cell culturing techniques are insufficient to model inflammatory cell adhesion on
      catheters used in the treatment of hydrocephalus and that changes to the
      ventricular microenvironment can alter the mechanisms of cellular adhesion. The
      HSCB represents a relevant test system and is an effective model system for the
      analysis of cellular adhesion and occlusion of shunt catheters.

PMID- 20051242
TI  - Deficiency of the negative immune regulator B7-H1 enhances inflammation and
      neuropathic pain after chronic constriction injury of mouse sciatic nerve.
AB  - Peripheral nerve injury induces a profound local inflammatory response that
      involves T cells and macrophages and augments the generation of neuropathic pain.
      The mechanisms underlying immune cell activation or inhibition in the peripheral
      nervous system, however, are unknown. The co-inhibitory molecule B7-H1 (PD-L1,
      CD274) attenuates immune cell proliferation and cytokine production and protects
      from inflammation-induced tissue damage. We analyzed the temporal gene expression
      profile of B7-H1 and different cytokines after chronic constriction injury (CCI)
      of the sciatic nerve, a lesion paradigm inducing neuropathic pain, by
      quantitative real-time polymerase chain reaction and immunohistochemistry in B7
      H1(-/-) mice and wild-type (WT) controls. B7-H1 mRNA was markedly induced in WT
      nerves after CCI, and macrophages could be identified as major B7-H1 source. The
      proinflammatory mediators tumor necrosis factor alpha (TNFalpha) and monocyte
      chemoattractant protein-1 (MCP-1) displayed a strong, but transient expression in
      degenerating nerves on day 1 after CCI in WT mice, while a biphasic expression
      peak on day 1 and day 28 was found in B7-H1(-/-) mice. Overall, TNFalpha and MCP
      1 levels in B7-H1-deficient nerves dramatically exceeded those in WT controls. In
      contrast, induction of the anti-inflammatory cytokine interleukin(IL)-10 was
      restricted to WT nerves. The observation that B7-H1 deficiency enhances
      inflammation upon CCI was further corroborated by immunohistochemistry showing
      increased numbers of T cells and macrophages in injured nerves from B7-H1(-/-)
      mice. Interestingly, mechanical hyperalgesia was more pronounced in the absence
      of B7-H1. Our study identifies B7-H1 as an important suppressor of the
      inflammatory response and neuropathic pain occurring after peripheral nerve
      injury.

PMID- 20051243
TI  - Effects of deep brain stimulation of the cerebellothalamic pathways on the sense
      of smell.
AB  - The cerebellum and the motor thalamus, connected by cerebellothalamic pathways,
      are traditionally considered part of the motor-control system. Yet, functional
      imaging studies and clinical studies including patients with cerebellar disease
      suggest an involvement of the cerebellum in olfaction. Additionally, there are
      anecdotal clinical reports of olfactory disturbances elicited by electrical
      stimulation of the motor thalamus and its neighbouring subthalamic region. Deep
      brain stimulation (DBS) targeting the cerebellothalamic pathways is an effective
      treatment for essential tremor (ET), which also offers the possibility to explore
      the involvement of cerebellothalamic pathways in the sense of smell. This may be
      important for patient care given the increased use of DBS for the treatment of
      tremor disorders. Therefore, 21 none-medicated patients with ET treated with DBS
      (13 bilateral, 8 unilateral) were examined with "Sniffin' Sticks," an established
      and reliable method for olfactory testing. Patients were studied either with DBS
      switched on and then off or in reversed order. DBS impaired odor threshold and,
      to a lesser extent, odor discrimination. These effects were sub-clinical as none
      of the patients reported changes in olfactory function. The findings, however,
      demonstrate that olfaction can be modulated in a circumscribed area of the
      posterior (sub-) thalamic region. We propose that the impairment of the odor
      threshold with DBS is related to effects on an olfacto-motor loop, while
      disturbed odor discrimination may be related to effects of DBS on short-term
      memory.

PMID- 20051244
TI  - A subunit of decaprenyl diphosphate synthase stabilizes octaprenyl diphosphate
      synthase in Escherichia coli by forming a high-molecular weight complex.
AB  - The length of the isoprenoid-side chain in ubiquinone, an essential component of
      the electron transport chain, is defined by poly-prenyl diphosphate synthase,
      which comprises either homomers (e.g., IspB in Escherichia coli) or heteromers
      (e.g., decaprenyl diphosphate synthase (Dps1) and D-less polyprenyl diphosphate
      synthase (Dlp1) in Schizosaccharomyces pombe and in humans). We found that
      expression of either dlp1 or dps1 recovered the thermo-sensitive growth of an E.
      coli ispB(R321A) mutant and restored IspB activity and production of Coenzyme Q
      8. IspB interacted with Dlp1 (or Dps1), forming a high-molecular weight complex
      that stabilized IspB, leading to full functionality.

PMID- 20051245
TI  - Assessing stress in animal populations: Do fecal and plasma glucocorticoids tell
      the same story?
AB  - Many studies have recently focused on stress as a marker of an animal's well
      being. Since animals respond to a stressor by increasing their glucocorticoid
      (GC) levels there has been much interest in measuring these hormones. Fecal GC
      analyses have been used in a wide range of studies as they are an easily
      obtained, non-invasive measure of these stress hormones. However, these analyses
      rest on two major assumptions. First, they assume that fecal GC metabolites
      reflect free, biologically active levels of GCs in the plasma. Second, they
      assume that differences in fecal GC metabolite levels among animals are an
      accurate reflection of their physiological state and thus of their ability to
      respond to a stressor. We tested these assumptions in a population of free
      ranging snowshoe hares (Lepus americanus) in the southwestern Yukon, from 2006 to
      2008. Both assumptions were verified. Plasma free cortisol levels mirrored bile
      and fecal cortisol metabolite (FCM) levels, but plasma total cortisol levels did
      not. Differences in FCM concentrations among hares robustly predicted their
      response to a hormonal challenge. Hares with higher FCM concentrations showed a
      greater resistance to the suppression of their free plasma cortisol following a
      dexamethasone injection and a more marked increase of free plasma cortisol
      following an ACTH injection. Furthermore, we found that changes in FCM
      concentrations in autumn and winter over two years reliably tracked changes in
      plasma free cortisol levels obtained from the hormonal challenge test. These
      results indicate that both fecal and plasma measures of an animal's stress
      physiology are concordant: they tell the same story.

PMID- 20051247
TI  - Brief postinfarction calcineurin blockade affects left ventricular remodeling and
      Ca2+ handling in the rat.
AB  - The role of calcineurin (CN) pathway in the post-myocardial infarction (MI) heart
      remains unclear. We investigated effects of early and brief inhibition of CN
      pathway with cyclosporine A (CsA) after MI on both immediate and delayed changes
      in left ventricular (LV) morphology, haemodynamics, and cardiomyocyte
      performance. CsA/saline was administered for 4 days, starting 24 h after MI/sham
      surgery in the rat. MI resulted in CN overactivity, peaking on day 3, accompanied
      by significant intracellular Ca(2+) overload due to marked decrease of NCX
      function. On day 7 and in week 8, CN activity decreased and normalized,
      respectively. It was accompanied by normalization of Ca(2+) handling parameters
      (only SERCA function was moderately decreased). CsA abolished post-MI CN
      overactivity, protected against Ca(2+) overload on day 3 and slightly improved
      SERCA function on day 7. Moreover, CsA reduced hypertrophy on days 3 and 7 after
      MI, increased wall stress on day 7 and in week 8, and lowered ejection fraction,
      augmented LV dilation as well increased mortality in week 8. Our study
      demonstrates that blockade of brief post-MI CN overactivity with CsA has delayed
      detrimental effects: increased mortality and worse LV function. CsA prevented
      early cardiomyocyte hypertrophy, decreased wall thickness and thus increased the
      wall stress, the main stimulus for detrimental LV dilation. Furthermore, CsA
      treatment prevented early Ca(2+) overload related to decreased NCX function. Role
      of this early Ca(2+) overload is unclear; it might be an element of positive
      feedback loop amplifying CN activation in post-MI heart.

PMID- 20051246
TI  - Oral progestin induces rapid, reversible suppression of ovarian activity in the
      cat.
AB  - The influence of oral progestin (altrenogest; ALT) on cat ovarian activity was
      studied using non-invasive fecal steroid monitoring. Queens were assigned to
      various ALT dosages: (1) 0mg/kg (control; n=5 cats); (2) 0.044 mg/kg (LOW; n=5);
      (3) 0.088 mg/kg (MID; n=6); or (4) 0.352 mg/kg (HIGH; n=6). Fecal estrogen and
      progestagen concentrations were quantified using enzyme immunoassays for 60 days
      before, 38 days during and 60 days after ALT treatment. Initiation of follicular
      activity was suppressed in all cats during progestin treatment, whereas controls
      continued to cycle normally. Females (n=6) with elevated fecal estrogens at
      treatment onset completed a normal follicular phase before returning to baseline
      and remained suppressed until treatment withdrawal. All cats receiving oral
      progestin re-initiated follicular activity after treatment, although MID cats
      experienced the most synchronized return (within 10-16 days). Mean baseline fecal
      estrogens and progestagens were higher (P<0.05) after treatment in HIGH, but not
      in LOW or MID cats compared to pre-treatment values. The results demonstrate
      that: (1) oral progestin rapidly suppresses initiation of follicular activity in
      the cat, but does not influence a follicular phase that exists before treatment
      initiation; and (2) queens return to normal follicular activity after progestin
      withdrawal. This study provides foundational information for research aimed at
      using progestin priming to improve ovarian response in felids scheduled for
      ovulation induction and assisted breeding.

PMID- 20051248
TI  - KChIP2 attenuates cardiac hypertrophy through regulation of Ito and intracellular
      calcium signaling.
AB  - Recent evidence shows that the auxiliary subunit KChIP2, which assembles with
      pore-forming Kv4-subunits, represents a new potential regulator of the cardiac
      calcium-independent transient outward potassium current (I(to)) density. In
      hypertrophy and heart failure, KChIP2 expression has been found to be
      significantly decreased. Our aim was to examine the role of KChIP2 in cardiac
      hypertrophy and the effect of restoring its expression on electrical remodeling
      and cardiac mechanical function using a combination of molecular, biochemical and
      gene targeting approaches. KChIP2 overexpression through gene transfer of
      Ad.KChIP2 in neonatal cardiomyocytes resulted in a significant increase in I(to)
      channel forming Kv4.2 and Kv4.3 protein levels. In vivo gene transfer of KChIP2
      in aortic banded adult rats showed that, compared to sham-operated or Ad.beta-gal
      transduced hearts, KChIP2 significantly attenuated the developed left ventricular
      hypertrophy, robustly increased I(to) densities, shortened action potential
      duration, and significantly altered myocyte mechanics by shortening contraction
      amplitudes and maximal rates of contraction and relaxation velocities and
      decreasing Ca(2+) transients. Interestingly, blocking I(to) with 4-aminopyridine
      in KChIP2-overexpressing adult cardiomyocytes significantly increased the Ca(2+)
      transients to control levels. One-day-old rat pups intracardially transduced with
      KChIP2 for two months then subjected to aortic banding for 6-8 weeks (to induce
      hypertrophy) showed similar echocardiographic, electrical and mechanical
      remodeling parameters. In addition, in cultured adult cardiomyocytes, KChIP2
      overexpression increased the expression of Ca(2+)-ATPase (SERCA2a) and sodium
      calcium exchanger but had no effect on ryanodine receptor 2 or phospholamban
      expression. In neonatal myocytes, KChIP2 notably reversed Ang II-induced
      hypertrophic changes in protein synthesis and MAP-kinase activation. It also
      significantly decreased calcineurin expression, NFATc1 expression and nuclear
      translocation and its downstream target, MCiP1.4. Altogether, these data show
      that KChIP2 can attenuate cardiac hypertrophy possibly through modulation of
      intracellular calcium concentration and calcineurin/NFAT pathway.

PMID- 20051249
TI  - Concurrent growth of phenotypic features: a phenomenological universalities
      approach.
AB  - Different physical features of an organism are often measured concurrently,
      because their correlations can be used as predictors of longevity, future health,
      or adaptability to an ecological niche. Since, in general, we do not know a
      priori if the temporal variations in the measured quantities are causally
      related, it may be useful to have a method that could help us to identify
      possible correlations and to obtain parameters that may vary from population to
      population. In this paper we develop a procedure that may detect underlying
      relationships. We do this by generalizing the recently introduced concept of
      phenomenological universalities to the complex field. In this generalization,
      allometric growth is described by a complex function, whose real and imaginary
      parts represent two phenotypic traits of the same organism. As particular
      solutions of the resulting problem, we obtain generalizations of the Gompertz and
      the von Bertalanffy-West growth equations. We then apply the procedure to two
      biological systems in order to show how to determine the existence of mutual
      interference between trait variations.

PMID- 20051250
TI  - Co-stimulation with TLR7/8 and TLR9 agonists induce down-regulation of innate
      immune responses in sheep blood mononuclear and B cells.
AB  - Toll-like receptors (TLRs) play an important role in the activation of innate and
      adaptive immune responses. Stimulation with multiple TLR agonists may result in
      synergistic, complimentary or inhibitory effects on innate immune responses. In
      this study, we investigated the effects of co-stimulation of sheep peripheral
      blood mononuclear cells (PBMC) and B cells with agonists for TLR3, 4, 7/8 and 9.
      Sheep PBMC stimulated with either CpG (TLR9 agonist) or RNA oligoribonucleotides
      ([ORNs], TLR7/8 agonist) exhibited significant IL-12 production, but only CpG
      induced IFNalpha, IgM and proliferative responses. In contrast, poly(I:C) (TLR3
      agonist) and LPS (TLR4 agonist) did not induce any of these responses.
      Interestingly, we observed that co-stimulation of PBMC with CpG+ORN or
      CpG+imiquimod (another TLR7/8 agonist) resulted in significant reduction in CpG
      induced IFNalpha production, B cell proliferation and IgM responses. Pre
      incubation of cells with CpG prior to exposure of the cells to imiquimod resulted
      in similar inhibitory responses indicating that the down-regulatory mechanisms
      are not associated with competition for cellular uptake or for receptors of the
      two agonists. Sheep B cells constitutively expressed TLR7, TLR8 and TLR9 mRNA
      transcripts, suggesting a possible role of TLR cross-talk in the down-regulatory
      mechanisms. Down-regulation of responses by co-stimulation with closely related
      TLRs may be a regulatory mechanism by which the host prevents overstimulation of
      innate immune responses.

PMID- 20051251
TI  - Sequence analysis of plasmid pIR52-1 from Lactobacillus helveticus R0052 and
      investigation of its origin of replication.
AB  - Lactobacillus helveticus R0052 is a bacterium used in commercial probiotic
      preparations. R0052 contains a small, cryptic plasmid comprised of eight open
      reading frames, four of which encode proteins of unknown function. Based on the
      sequence of the replication initiation protein RepA, pIR52-1 is a member of the
      recently described RepA_N family of Gram-positive theta-replicating plasmids. The
      repA gene of pIR52-1 is the minimal origin of replication for L. helveticus and
      other Lactobacillus hosts. Additionally, pIR52-1 belongs to a subgroup of the
      RepA_N plasmid family which have RepA proteins of high amino acid identity and a
      conserved, non-coding element upstream of repA which, in pIR52-1, is responsible
      for the control of plasmid copy number and contributes to plasmid maintenance.

PMID- 20051252
TI  - Environmental factors and genetic susceptibility promote urinary bladder cancer.
AB  - Cancer of the urinary bladder is the second most common malignancy of the
      genitourinary tract, currently accounting for up to 5% of all newly diagnosed
      tumours in the western world. Urinary bladder carcinogenesis seems to develop
      from the interaction of environmental exposure and genetic susceptibility.
      Smoking, specific industrial chemicals, dietary nitrates and arsenic represent
      the most important exogenous risk factors. Chromosomal abnormalities, silencing
      of certain genes by abnormal methylation of their promoter region, alterations in
      tumour suppressor genes and proto-oncogenes that induce uncontrolled cell
      proliferation and reduced apoptosis, are molecular mechanisms that have been
      reported in bladder carcinogenesis. In this article, we discuss the environmental
      risk factors of bladder cancer and we review the genetic and epigenetic
      alterations, including aberrant DNA methylation and deregulation of microRNAs
      expression. We also discuss the role of p53 and retinoblastoma suppressor genes
      in disease progression. Finally, we present recent reports on the use of
      molecular profiling to predict disease stage and grade and direct targeted
      therapy.

PMID- 20051253
TI  - In vivo methylmercury exposure induced long-lasting epileptiform activity in
      layer II/III neurons in cortical slices from the rat.
AB  - Prenatal and postnatal methylmercury (MeHg) exposure has been shown to increase
      neuronal excitability and seizure susceptibility. To determine if early postnatal
      MeHg exposure causes a similar effect, we examined changes in field potentials in
      layer II/III neurons in cortical slices of rat following in vivo MeHg treatment.
      Rats received 0 (0.9% NaCl), 0.75 mg/kg/day or 1.5mg/kg/day MeHg subcutaneously
      for 15 or 30 days beginning on postnatal day 5, after which cortical slices were
      prepared for field potential recordings. In slices from rats treated with
      vehicle, single pulse stimulation of layer IV of cortical slices induced a
      typical field excitatory postsynaptic potential (fEPSP) with a single spike. This
      type of fEPSPs was also seen in slices from rats with 15 day treatment with 0.75
      mg/kg/day or 1.5mg/kg/day MeHg. However, 30-day treatment with either MeHg dose
      resulted in fEPSPs with multiple spikes (epileptiform activity) in 40% of animals
      examined. This epileptiform activity remained observable in 50-60% animals in
      which MeHg exposure had been terminated for 30 days. However, slices from control
      animals still showed fEPSPs with single spike. Thus, these data suggest that
      postnatal MeHg exposure in vivo altered neuronal excitability and induced a long
      lasting hyperexcitability in cortical neurons.

PMID- 20051254
TI  - Paeonol, the main active principles of Paeonia moutan, ameliorates alcoholic
      steatohepatitis in mice.
AB  - AIM OF STUDY: Paeonol, a major phenolic component of Moutan Cortex, is
      traditionally used as a Chinese herbal medicine in various diseases including
      hepatitis. Evidence shows that paeonol has anti-inflammatory, anti-tumor, and
      anti-atherosclerosis effects. However, the effect of paeonol on alcoholic liver
      injury remains obscure. The present investigation was designed to determine the
      effects of paeonol on alcohol-induced hepatic injury in mice. MATERIALS AND
      METHODS: The degree of alcoholic liver injury was evaluated biochemically by
      measuring serum markers and pathological examination. Real-time PCR and ELISA
      methods were used to check the expression of cytokines. Western blotting was used
      to check CYP 450 expression. RESULTS: Treatment with paeonol significantly
      attenuated the level of serum aminotransferase, reduced the severe extent of
      hepatic cell damage, steatosis, and the infiltration of inflammatory cells in a
      model of alcoholic liver injury (P<0.05). Interestingly, paeonol markedly
      decreased hepatic mRNA expression of lipogenic genes (P<0.05) while had no effect
      on protein expression of hepatic CYP2E1. Furthermore, paeonol significantly
      decreased serum and tissue inflammatory cytokine levels, tissue lipid
      peroxidation, neutrophil infiltration and inhibited the apoptosis of hepatocytes
      (P<0.05). Kupffer cells isolated from ethanol-fed mice produced high amounts of
      tumor necrosis factor alpha, whereas Kupffer cells from paeonol treatment ethanol
      fed mice produced less tumor necrosis factor alpha (P<0.05). CONCLUSIONS: These
      findings suggest that paeonol may represent a novel, protective strategy against
      alcoholic liver injury by attenuating hepatic steatosis, inflammatory response
      and apoptosis.

PMID- 20051255
TI  - In vivo pharmacokinetics of bakuchiol after oral administration of bakuchiol
      extraction in rat plasma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (Fabaceae) was a
      traditional Chinese medicine for the treatment of various skin diseases such as
      psoriasis, vitiligo and chronic graft-versus-host, and has been proved to show
      anticancer, cytotoxic, anti-bacterial, cardiac, diaphoretic, diuretic, stimulant,
      aphrodisiac and tonic effects. Bakuchiol was one of the main active ingredients
      of this traditional Chinese medicine. AIM OF THE STUDY: In this paper,
      pharmacokinetic study was conducted to obtain pharmacokinetic parameters of
      bakuchiol. MATERIALS AND METHODS: Bakuchiol was enriched using resin inform the
      ethanol extract of Psoralea corylifolia L., HPLC-UV was used to determine the
      concentration of bakuchiol in rat plasma at different time points after
      administration. The main pharmacokinetic parameters of bakuchiol in rat were
      obtained based on the analysis of the plasma sample. RESULTS: The
      pharmacokinetics of bakuchiol was fitted with a two-compartment model and it was
      eliminated relative slowly in rats. CONCLUSIONS: The HPLC-UV method was
      successfully applied to study the pharmacokinetics of bakuchiol in rats.

PMID- 20051256
TI  - Pharmacokinetic comparisons of typical constituents in white peony root and
      sulfur fumigated white peony root after oral administration to mice.
AB  - AIM: White peony root and sulfur fumigated white peony root are produced by
      different processing methods from the root of Paeonia lactiflora Pall, but the
      two traditional Chinese medicines are used under the same common name white peony
      root. In order to clarify the influence of sulfur fumigation on pharmacokinetics
      of the main monoterpene glucoside components in white peony root, an
      investigation was carried out to compare the pharmacokinetics of sodium
      paeoniflorin sulfonate (1) and paeoniflorin (2), benzoylpaeoniflorin sulfonate
      (3) and benzoylpaeoniflorin (4), as well as 1 in sulfur fumigated white peony
      root extract (SWPE) and 2 in white peony root extract (WPE). MATERIALS AND
      METHODS: A high-performance liquid chromatographic (HPLC) assay was developed to
      determine the plasma concentrations of the four analytes. Kunming species of mice
      were orally administered the four compounds and the two extracts with
      approximately the same dose. RESULTS: It was found that C(max) and AUC of 1 and 3
      were increased (P<0.05), and the T(max) and t(1/2) were prolonged (P<0.05) by
      comparison with that of 2. Similar results were also observed for the
      pharmacokinetics parameters of 1 in SWPE and 2 in WPE. However,
      benzoylpaeoniflorin (4) was not detected in plasma collected at certain intervals
      after administered orally to mice. CONCLUSIONS: These results indicate that
      sulfonation of the monoterpene components could improve the bioavailability and
      delay the absorption of them in mice.

PMID- 20051257
TI  - Effect of Wujijing Oral Liquid on menstrual disturbance of women.
AB  - OBJECTIVE: Wujijing Oral Liquid (WJJ) contained principally the flesh essence of
      the black-boned chicken. As a kind of food and medicine in China, it was used to
      treat the menstrual disturbance traditionally, but the exact mechanism of the
      action was not yet clear. The clinical effects of the WJJ on the symptoms of the
      menstrual disturbance and the reproductive hormones were studied in this paper.
      MATERIALS AND METHODS: The 53 women with the menstrual disturbance were selected
      as the study object, and then they were randomly divided to receive either WJJ
      10mL twice daily (n=28) or the placebo (n=25) from the 1st day after menstrual
      flow for 2 menstrual cycles. On the 1st day after the discontinuation of the
      medication but before the treatment, the scores for the menstrual pattern and the
      related symptoms were obtained and the blood samples were collected to test the
      reproductive hormones. The serum levels of the follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), prolactin (PRL) and estradiol (E2) were examined
      by enzyme-linked immunosorbent assay (ELISA). The levels of progesterone (P) and
      testosterone (T) in serum were measured by the radioimmunoassay. RESULTS: The
      score for the primary and related symptoms of the menstruation was increased
      significantly among patients treated with the WJJ. The differences on the FSH,
      PRL, and E2 levels of patients were significant before and after the treatment
      with WJJ. Comparing the WJJ group and the placebo group, the levels of P and T
      differed significantly after treatment. The oral liquid of WJJ was found to be
      safe, as it did not cause any change in the hepatic and renal functional
      parameters. CONCLUSION: The oral liquid of Wujijing could improve the menstrual
      disturbance and were generally safe and well tolerated. The possible mechanism
      could be associated with its effects in reinforcing the kidney and regulating the
      hypothalamus-pituitary-ovary axis (HPOA).

PMID- 20051258
TI  - Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate
      fraction of Acorus calamus in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The radix of Acorus calamus L. (AC) is widely
      used in the therapy of diabetes in traditional folk medicine of America and
      Indonesia, and we previously reported the insulin sensitizing activity of the
      ethyl acetate fraction of AC (ACE). AIM OF THE STUDY: To investigate the insulin
      releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.
      MATERIALS AND METHODS: Insulin releasing and alpha-glucosidase inhibitory effects
      of different fractions from AC were detected in vitro using HIT-T15 cell line and
      alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose
      were detected in fasted and glucose/amylum challenged normal mice. RESULTS: AC
      and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in
      vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum
      glucose, and suppressed the increase of blood glucose levels after 2g/kg glucose
      loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited
      alpha-glucosidase activity in vitro with an IC(50) of 0.41 microg/ml, and
      100mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg
      amylum loading in normal mice. CONCLUSIONS: Apart from its insulin sensitizing
      effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and
      alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and
      cardiovascular complications.

PMID- 20051259
TI  - Anxiolytic and sedative activities of Passiflora edulis f. flavicarpa.
AB  - AIM OF THE STUDY: Many plants in the genus Passiflora have long been used in
      traditional folk medicines as a remedy for many neurogenic diseases in many
      countries. A number of species of the genus was studied about their
      neuropharmacological activities, but the results were inconsistent. No literature
      reported neuropharmacological studies on Passiflora edulis f. flavicarpa as yet.
      The present study was aimed at evaluating the anxiolytic and sedative activities
      of Passiflora edulis f. flavicarpa. MATERIALS AND METHODS: Swiss albino mice were
      used as experimental animals in elevated plus-maze (EPM) test and spontaneous
      activity (SA) test to assay the behavioral effects of ethanolic extract (EE) of
      the aerial part of Passiflora edulis f. flavicarpa and its fractions, viz. petrol
      ether extract (PEE), ethyl acetate extract (EAE), n-BuOH extract (BE) and aqueous
      extract (AE), together with subfractions of BE, viz. BEF-I, BEF-II, BEF-III, BEF
      IV and isoorientin, a flavonoid component isolated from BEF-III. RESULTS: In the
      EPM test, single-dose oral administration of EE (300 mg/kg and 400mg/kg), BE (125
      mg/kg and 200mg/kg), AE (200mg/kg and 300 mg/kg), BEF-I (200mg/kg), BEF-II
      (200mg/kg), BEF-III (100mg/kg), or isoorientin (20mg/kg) resulted in anxiolytic
      like effects, but a sedative-like activity was produced at higher doses, such as
      300 mg/kg of BE, 200mg/kg of BEF-III, or 40 mg/kg and 80 mg/kg of isoorientin.
      The results of the SA test manifested that treatment with 400mg/kg of EE, 300
      mg/kg of BE, or 40 mg/kg and 80 mg/kg of isoorientin compromised motor activity
      in mice, which are in line with the results of the EPM test. CONCLUSIONS: The
      aerial part of Passiflora edulis f. flavicarpa was anxiolytic at low dose but
      sedative at high dose. Flavonoids are important active constituents. Since AE
      contained little flavonoids, it was conjectured that there were other components
      responsible for the anxiolytic effect of Passiflora edulis f. flavicarpa besides
      flavonoids.

PMID- 20051260
TI  - The dual actions of Sanmiao wan as a hypouricemic agent: down-regulation of
      hepatic XOD and renal mURAT1 in hyperuricemic mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Sanmiao wan (SMW) is widely used for the
      treatment of gout and hyperuricemia in traditional Chinese medicine. AIM OF THE
      STUDY: The aim of the present study was to investigate the hypouricemic effects
      of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic
      mice. MATERIALS AND METHODS: SMW at 489, 978 and 1956 mg/kg was orally
      administered to hyperuricemic and normal mice, and standard drug allopurinol
      (2.5mg/kg) was served as a positive control. The effects of SMW on serum, urine
      and liver levels of uric acid, serum levels of creatinine, and activity of
      hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of
      SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1
      (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting
      methods, respectively. RESULTS: SMW significantly reduced uric acid levels in
      serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in
      hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1
      mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced
      elevation in serum creatinine levels of mice. However, SMW did not show any
      effects in normal mice. CONCLUSION: These findings suggested that SMW produced
      dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid
      production and down-regulating renal mURAT1 to decrease urate reabsorption and
      enhance urate excretion in hyperuricemic mice.

PMID- 20051261
TI  - Anti-inflammatory properties of phenolic compounds and crude extract from
      Porphyra dentata.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Porphyra dentata, a red edible seaweed, has long
      been used worldwide in folk medicine for the treatment of inflammatory diseases
      such as hypersensitivity, lymphadenitis, bronchitis. AIMS OF STUDY: To clarify
      the anti-inflammatory role of Porphyra dentata crude extract and its identified
      phenolic compounds by investigating their effect on the nitric oxide
      (NO)/inducible nitric oxide synthase (iNOS) transcription pathway in macrophage
      RAW 264.7 cells. MATERIALS AND METHODS: Porphyra dentata crude extract was
      prepared with methanol. High performance liquid chromatography (HPLC) hyphenated
      to electrospray ionization mass spectrometry (ESI-MS) and UV detection were
      utilized to analyze the extract fingerprints. Nitrite measurement, iNOS promoter
      activity and nuclear factor-kappaB (NF-kappaB) enhancer activity were used to
      assess the anti-inflammatory effect in lipopolysaccharide (LPS) challenged mouse
      RAW 264.7 cell line. RESULTS: Phenolic compounds (catechol, rutin and hesperidin)
      were identified in the crude extract of Porphyra dentata. The crude extract and
      the phenolic compounds inhibited the production of NO in LPS-stimulated RAW 264.7
      cells. Catechol was a more potent suppressor of the up-regulation of iNOS
      promoter and NF-kappaB enhancer than rutin and yet, hesperidin alone failed to
      inhibit either activity. CONCLUSION: Our results indicate that catechol and
      rutin, but not hesperidin, are primary bioactive phenolic compounds in the crude
      extract to suppress NO production in LPS-stimulated macrophages via NF-kappaB
      dependent iNOS gene transcription. The data also explain the anti-inflammatory
      use and possible mechanism of Porphyra dentata in iNOS implicated diseases.

PMID- 20051262
TI  - Biochemical mechanism of Wu-Zi-Yan-Zong-Wan, a traditional Chinese herbal
      formula, against alcohol-induced oxidative damage in CYP2E1 cDNA-transfected
      HepG2 (E47) cells.
AB  - AIM OF THE STUDY: Wu-Zi-Yan-Zong-Wan (WZ) is a traditional Chinese herbal formula
      which is commonly used for treating patients with "Yang deficiency". In the
      present study, the effect of WZ on ethanol-induced toxicity in CYP2E1 cDNA
      transfected HepG2 (E47) cells was investigated. MATERIALS AND METHODS: WZ extract
      was obtained by extracting the herbal powder with 50% ethanol (v/v, in water) and
      the effect of the extract on ethanol-induced toxicity was investigated in
      cultured cells. RESULTS: The treatment with WZ extract (12.5-200 microg/mL) for
      24h dose-dependently protected against ethanol-induced toxicity in E47 cells, as
      evidenced by the enhanced cell viability and decreased extent of lactate
      dehydrogeanse leakage. The cytoprotection against ethanol-induced toxicity was
      associated with decreases in the extents of reactive oxygen species production
      and lipid peroxidation, as well as increases in mitochondrial reduced glutathione
      and membrane potential. In addition, WZ extract treatment also suppressed the
      formation of DNA fragments in ethanol-intoxicated E47 cells. CONCLUSIONS: WZ
      extract was found to protect against the ethanol-induced toxicity in E47 cells,
      possibly by virtues of its antioxidant activity.

PMID- 20051263
TI  - Role of brain macrophages on IL-1beta and fatigue following eccentric exercise
      induced muscle damage.
AB  - Fatigue associated with recovery from muscle damage has recently been linked to
      increases in brain and muscle proinflammatory cytokines. However, little is known
      regarding the origin of these cytokines. Since macrophage-like cells in the brain
      are a primary source of cytokines, we used a brain specific macrophage depletion
      technique involving liposome encapsulated clodronate (CLD) to examine the role of
      macrophages on brain IL-1beta and fatigue following eccentric exercise-induced
      muscle damage. Mice were assigned to six groups: Downhill saline (DWNSAL),
      downhill clodronate (DWNCLD), uphill saline (UPSAL), uphill clodronate (UPCLD),
      non-running saline (CONSAL) or non-running clodronate (CONCLD). Mice were given
      intracerebroventricular (ICV) (10 microL) injections of clodronate-filled
      liposomes (CLD) to deplete macrophages, or saline-filled liposomes (SAL) and run
      on a treadmill at 22m/min and -14% (DWN) or 14% (UP) grade for 150 min. A subset
      of uphill and downhill running mice (n=40) was then run to fatigue on a treadmill
      at 36m/min, 8% grade at 24h after the uphill and downhill runs. A second subset
      of uphill, downhill, and control mice (n=30) was sacrificed 24h after the run for
      analysis of brain IL-1beta concentration. Histological examination confirmed
      previous reports that CLD administration reduced perivascular and meningeal
      macrophage subsets in the brain. CLD reduced IL-1beta concentration in the cortex
      of DWN mice (P<0.05), which was associated with enhanced treadmill performance
      24h after both uphill and downhill runs (P<0.05) although the magnitude was
      greater following the downhill run. These results suggest that brain macrophages
      can contribute to the increase in brain IL-1beta and fatigue that are associated
      with recovery from exercise-induced muscle damage.

PMID- 20051264
TI  - Spatial expression profiles in the Xenopus laevis oocytes measured with qPCR
      tomography.
AB  - qPCR tomography was developed to study mRNA localization in complex biological
      samples that are embedded and cryo-sectioned. After total RNA extraction and
      reverse transcription, the spatial profiles of mRNAs and other functional RNAs
      were determined by qPCR. The Xenopus laevis oocyte was selected as model, because
      of its large size (more than 1mm) and large amount of total RNA (approximately
      5microg). Fifteen sections along the animal-vegetal axis were cut and prepared
      for quantification of 31 RNA targets using the high-throughput real-time RT-PCR
      (qPCR) BioMark platform. mRNAs were found to have two localization patterns,
      animal/central or vegetal. Because of the high resolution in sectioning, it was
      possible to distinguish two subgroups of the vegetal gene patterns: germ plasm
      determinant pattern and profile of other vegetal genes.

PMID- 20051265
TI  - Analysis of histones and chromatin in Xenopus laevis egg and oocyte extracts.
AB  - Histones are the major protein components of chromatin, the physiological form of
      the genome in all eukaryotic cells. Chromatin is the substrate of information
      directed biological processes, such as gene regulation and transcription,
      replication, and mitosis. A long-standing experimental model system to study many
      of these processes is the extract made from the eggs of the anuran Xenopus
      laevis. Since work in recent years has solidified the importance of post
      translational modification of histones in directing biological processes, the
      study of histones in a biochemically dissectible model such as Xenopus is crucial
      for the understanding of their biological significance. Here we present a
      rationale and methods for isolating and studying histones and chromatin in
      different Xenopus egg and oocyte extracts. In particular, we present protocols
      for the preparation of: cell-free egg and oocyte extract; nucleoplasmic extract
      ("NPE"); biochemical purification of maternally-deposited, stored histones in the
      oocyte and the egg; assembly of pronuclei in egg extract and the isolation of
      pronuclear chromatin and histones; and an extract chromatin assembly assay. We
      also demonstrate aspects of the variability of the system to be mindful of when
      working with extract and the importance of proper laboratory temperature in
      preparing quality extracts. We expect that these methods will be of use in
      promoting further understanding of embryonic chromatin in a unique experimental
      system.

PMID- 20051267
TI  - The crystal structure of Escherichia coli spermidine synthase SpeE reveals a
      unique substrate-binding pocket.
AB  - Polyamines are essential in all branches of life. Biosynthesis of spermidine, one
      of the most ubiquitous polyamines, is catalyzed by spermidine synthase (SpeE).
      Although the function of this enzyme from Escherichia coli has been thoroughly
      characterised, its structural details remain unknown. Here, we report the crystal
      structure of E. coli SpeE and study its interaction with the ligands by
      isothermal titration calorimetry and computational modelling. SpeE consists of
      two domains - a small N-terminal beta-strand domain, and a C-terminal catalytic
      domain that adopts a canonical methyltransferase (MTase) Rossmann fold. The
      protein forms a dimer in the crystal and in solution. Structural comparison of E.
      coli SpeE to its homologs reveals that it has a large and unique substrate
      binding cleft that may account for its lower amine substrate specificity.

PMID- 20051266
TI  - Using fluorometry and ion-sensitive microelectrodes to study the functional
      expression of heterologously-expressed ion channels and transporters in Xenopus
      oocytes.
AB  - The Xenopus laevis oocyte is a model system for the electrophysiological study of
      exogenous ion transporters. Three main reasons make the oocyte suitable for this
      purpose: (a) it has a large cell size (approximately 1mm diameter), (b) it has an
      established capacity to produce-from microinjected mRNAs or cRNAs-exogenous ion
      transporters with close-to-physiological post-translational modifications and
      actions, and (c) its membranes contain endogenous ion-transport activities which
      are usually smaller in magnitude than the activities of exogenously-expressed ion
      transporters. The expression of ion transporters as green fluorescent protein
      fusions allows the fluorometric assay of transporter yield in living oocytes.
      Monitoring of transporter-mediated movement of ions such as Cl(-), H(+) (and
      hence base equivalents like OH(-) and HCO(3)(-)), K(+), and Na(+) is achieved by
      positioning the tips of ion-sensitive microelectrodes inside the oocyte and/or at
      the surface of the oocyte plasma membrane. The use of ion-sensitive electrodes is
      critical for studying net ion-movements mediated by electroneutral transporters.
      The combined use of fluorometry and electrophysiology expedites transporter study
      by allowing measurement of transporter yield prior to electrophysiological study
      and correlation of relative transporter yield with transport rates.

PMID- 20051268
TI  - Circadian rhythms in Neurospora crassa: dynamics of the clock component frequency
      visualized using a fluorescent reporter.
AB  - The frequency (frq) gene of Neurospora crassa has long been considered essential
      to the function of this organism's circadian rhythm. Increasingly, deciphering
      the coupling of core oscillator genes such as frq to the output pathways of the
      circadian rhythm has become a major focus of circadian research. To address this
      coupling it is critical to have a reporter of circadian activity that can deliver
      high resolution spatial and temporal information about the dynamics of core
      oscillatory proteins such as FRQ. However, due to the difficulty of studying the
      expression of circadian rhythm genes in aerobic N. crassa cultures, little is
      known about the dynamics of this gene under physiologically realistic conditions.
      To address these issues we report a fluorescent fusion to the frq gene using a
      codon optimized version of the mCherry gene. To trace the expression and
      accumulation of FRQ-mCherryNC (FRQ-mCh) during the circadian rhythm, growing
      vegetative hyphae were scanned every hour under confocal microscopy (100x).
      Fluorescence of FRQ-mCh was detected only at the growing edge of the colony, and
      located in the cytoplasm and nuclei of vegetative hyphae for a distance of
      approximately 150-200microm from the apices of leading hyphae. When driven by the
      frq promoter, apparently there was also a second FRQ entrance into the nucleus
      during the circadian cycle; however the second entrance had a lower accumulation
      level than the first entrance. Thus this fluorescent fusion protein has proven
      useful in tracking the spatial dynamics of the frq protein and has indicated that
      the dynamics of the FRQ protein's nuclear trafficking may be more complex than
      previously realized.

PMID- 20051269
TI  - Modeling and optimization of a multi-product biosynthesis factory for multiple
      objectives.
AB  - Genetic algorithms and optimization in general, enable us to probe deeper into
      the metabolic pathway recipe for multi-product biosynthesis. An augmented model
      for optimizing serine and tryptophan flux ratios simultaneously in Escherichia
      coli, was developed by linking the dynamic tryptophan operon model and aromatic
      amino acid-tryptophan biosynthesis pathways to the central carbon metabolism
      model. Six new kinetic parameters of the augmented model were estimated with
      considerations of available experimental data and other published works. Major
      differences between calculated and reference concentrations and fluxes were
      explained. Sensitivities and underlying competition among fluxes for carbon
      sources were consistent with intuitive expectations based on metabolic network
      and previous results. Biosynthesis rates of serine and tryptophan were
      simultaneously maximized using the augmented model via concurrent gene knockout
      and manipulation. The optimization results were obtained using the elitist non
      dominant sorting genetic algorithm (NSGA-II) supported by pattern recognition
      heuristics. A range of Pareto-optimal enzyme activities regulating the amino
      acids biosynthesis was successfully obtained and elucidated wherever possible vis
      a-vis fermentation work based on recombinant DNA technology. The predicted
      potential improvements in various metabolic pathway recipes using the multi
      objective optimization strategy were highlighted and discussed in detail.

PMID- 20051270
TI  - Covalently immobilized RGD gradient on PEG hydrogel scaffold influences cell
      migration parameters.
AB  - Understanding the influence of a controlled spatial distribution of biological
      cues on cell activities can be useful to design "cell instructive" materials,
      able to control and guide the formation of engineered tissues in vivo and in
      vitro. To this purpose, biochemical and mechanical properties of the resulting
      biomaterial must be carefully designed and controlled. In this work, the effect
      of covalently immobilized RGD peptide gradients on poly(ethylene glycol)
      diacrylate hydrogels on cell behaviour was studied. We set up a mechanical device
      generating gradients based on a fluidic chamber. Cell response to RGD gradients
      with different slope (0.7, 1 and 2 mM cm(-1)) was qualitatively and
      quantitatively assessed by evaluating cell adhesion and, in particular, cell
      migration, compared to cells seeded on hydrogels with uniform distribution of RGD
      peptides. To evaluate the influence of RGD gradient and to exclude any
      concentration effect on cell response, all analyses were carried out in a
      specific region of the gradients which displayed the same average concentration
      of RGD (1.5 mM). Results suggest that cells recognize the RGD gradient and adhere
      onto it assuming a stretched shape. Moreover, cells tend to migrate in the
      direction of the gradient, as their speed is higher than that of cells migrating
      on hydrogels with a uniform distribution of RGD and increases by increasing RGD
      gradient steepness. This increment is due to an augmentation of bias speed
      component of the mean squared speed, that is, the drift of the cell population
      migrating on the anisotropic surface provided by the RGD gradient.

PMID- 20051271
TI  - Critical discussion of the results from different corrosion studies of Mg and Mg
      alloys for biomaterial applications.
AB  - The aim of this work was to collect and compare data from different published
      reports which focused on the description of the influence of different
      electrochemical setups for the assessment of magnesium corrosion. Based on this,
      a comparison with our own results, obtained for LAE 442 and AZ 31, was made and
      discussed. As the collection of data has shown, the reported inconsistencies
      between in vivo and electrochemical data depend greatly on the electrochemical
      medium used, on the alloy composition and on surface preparation. Nevertheless,
      these differences also exist when comparing different in vitro results using
      different methodologies and even different Mg alloys, and need therefore to be
      discussed more thoroughly in the future. The simulation of transport conditions
      of the in vivo interface should become a focus of research interest in order to
      gain a better understanding of the influence of connecting processes on the
      degradation of the biomaterials.

PMID- 20051272
TI  - A facile method to fabricate poly(L-lactide) nano-fibrous morphologies by phase
      inversion.
AB  - Scaffolds with a nano-fibrous morphology are favored for certain tissue
      engineering applications as this morphology mimics the tissue's natural
      extracellular matrix secreted by the cells, which consists of mainly collagen
      fibers with diameters ranging from 50 to 400 nm. Porous poly(L-lactide) (PLLA)
      scaffolds obtained by phase inversion methods generally have a solid-wall pore
      morphology. In contrast, this work presents a facile method to fabricate highly
      porous and highly interconnected nano-fibrous scaffold sheets by phase inversion
      using PLLA of very high molecular weight (5.7x10(5) g mol(-1)). The scaffold
      sheets consist of nano-fibers within the desired range of 50-500 nm. When
      applying phase separation micromolding as a fabrication method besides the porous
      nano-fibrous morphology, an additional topography can be introduced into these
      sheets. Culturing of C2C12 pre-myoblasts on these nano-fibrous sheets reveals
      very good cell adhesion, morphology and proliferation. Excellent alignment of the
      cells is induced by fabrication of 25 microm wide microchannels in these sheets.
      These results warrant further evaluation of these sheets as tissue engineering
      scaffolds.

PMID- 20051273
TI  - Hyaluronan scaffolds: a balance between backbone functionalization and
      bioactivity.
AB  - Development of biomaterials that provide mechanical and molecular cues for wound
      healing and regeneration must meet several design parameters. In addition to high
      biocompatibility, biomaterials should possess suitable porosity as well as the
      ability to be chemically tailored to control parameters including
      biodegradability and bioactivity. These characteristics were studied in
      hyaluronan (HA), a natural polymer found in the body. HA was modified with thiol
      cross-linking sites to form a stable hydrogel scaffold to examine effects in in
      vitro cortical cell growth. HA with 20% and 44% thiolation was used to make gels
      at 0.5%, 0.75%, 1%, and 1.25% (w/v). Results indicate that the bioactivity of the
      HA after functionalization, as determined by degree of substitution (HA
      thiolation), has a greater effect on neurite outgrowth than does gel stiffness.
      The lower substituted HA (20%) promoted greater neurite growth as compared to the
      higher substituted HA (44%).

PMID- 20051274
TI  - Functional and association analysis of frizzled 1 (FZD1) promoter haplotypes with
      femoral neck geometry.
AB  - Frizzleds are receptors for Wnt signaling and are involved in skeletal
      morphogenesis. Little is known about the transcriptional regulation of frizzleds
      in bone cells. In the current study, we determined if two common and potentially
      functional genetic variants (rs2232157, rs2232158) in the frizzled-1 (FZD1)
      promoter region and their haplotypes influence FZD1 promoter activity in human
      osteoblast-like cells. We also determined if these variants are associated with
      femoral neck bone mineral density (BMD) and geometry in 1319 African ancestry men
      aged > or =40 years. Real-time quantitative PCR and western blot analysis
      demonstrated FZD1 mRNA and protein expression in the human osteoblast-like cell
      lines, MG63 and SaOS-2. Promoter activity was next assessed by transient
      expression of haplotype specific FZD1 promoter reporter plasmids in these cells.
      In comparison to the common GG haplotype, promoter activity was 3-fold higher for
      the TC haplotype in both cell lines (p<0.05). We previously demonstrated that
      rs2232158 is associated with differential FZD1 promoter activity and Egr1 binding
      and thus focused further functional analyses on the rs2232157 G-to-T
      polymorphism. Electrophoretic mobility shift assay demonstrated that distinct
      nuclear protein complexes were associated with rs2232157 in an allele specific
      manner. Bioinformatics analysis predicted that the G to T transversion creates an
      E2F1 binding site, further supporting the functional significance of rs2232157 in
      FZD1 promoter regulation. Individual SNPs and haplotypes were not associated with
      femoral neck BMD. The TC haplotype was associated with larger subperiosteal width
      and greater CSMI (p<0.05). These results suggest that FZD1 expression is
      regulated in a haplotype-dependent manner in osteoblasts and that these same
      haplotypes may be associated with biomechanical indices of bone strength.

PMID- 20051275
TI  - Changes in trabecular microarchitecture in postmenopausal women on bisphosphonate
      therapy.
AB  - PURPOSE: In addition to bone mineral density (BMD), trabecular microstructure
      contributes to skeletal strength. Our goal was to examine changes in trabecular
      microstructure in women on therapy. MATERIALS AND METHODS: We followed 10
      postmenopausal women receiving a bisphosphonate, risedronate (35 mg once weekly),
      over 12 months and examined trabecular microarchitecture with high resolution
      wrist MR images (hr-MRI). MRI parameters included bone volume/total volume
      (BV/TV), surface density (representing plates), curve density (representing
      rods), surface-to-curve ratio and erosion index (depicting deterioration). We
      assessed BMD of the spine, hip and radius and markers of bone turnover. RESULTS:
      Women had been receiving bisphosphonate therapy for 43+/-9 months (mean+/-SD)
      prior to the first MRI. Indices of hr-MRI demonstrated improvement in surface-to
      curve ratio (13.0%) and a decrease in erosion index (12.1%) consistent with less
      deterioration (both p<0.05). BMD of the spine, hip and radius and markers of bone
      turnover remained stable. Parameters of hr-MRI were associated with 1/3 distal
      radius BMD (correlation coefficient 0.71 to 0.86, p<0.05). DISCUSSION: We
      conclude that hr-MRI of the radius demonstrates improvements in trabecular
      microstructure not appreciated by conventional BMD and provides additional
      information on parameters that contribute to structural integrity in patients on
      antiresorptive therapy.

PMID- 20051277
TI  - Heterologous HIV-based lentiviral/adenoviral vectors immunizations result in
      enhanced HIV-specific immunity.
AB  - Viral vectors are considered as one of the major means for the induction of
      strong immune responses against recombinant antigens by genetic immunization.
      Among these, lentiviral vectors are particularly attractive vehicles, as they can
      infect a wide variety of cells and can transduce replicating as well as non
      replicating cells. We have engineered VRX1023, an HIV-1-based lentiviral vector
      (LV) vaccine candidate, to deliver HIV-1 Gag, Pol and Rev antigens under control
      of the native LTR promoter. While VRX1023 has been shown to elicit strong cell
      mediated and humoral immunity as a stand-alone vaccine, we report here its
      combination in a heterologous prime-boost approach. Its combination with an
      adenovirus serotype 5 (Ad5)-based vector in the mouse model increased the
      frequency and polyfunctionality of HIV-specific CD4+ and CD8+ T cells. Homologous
      prime-boost regimens induced high levels of anti-vector neutralizing antibodies
      in Ad5-immunized mice, whereas the VSV-G-pseudotyped VRX1023 LV elicited low
      levels of anti-lentiviral vector neutralization. In addition, the heterologous
      prime-boost strategy resulted in a 5-fold reduction in Ad5-specific vector
      neutralization as compared to Ad5 homologous immunization. In conclusion, this
      study demonstrates that LV and Ad5 vector candidates can be combined in a
      heterologous immunization regimen, yielding dramatically improved immunogenicity
      while overcoming anti-vector immunity. These findings may have implications for
      the development of HIV vaccine regimens in populations with elevated Ad5
      seroprevalence or when repeated vector administrations are required.

PMID- 20051278
TI  - Hysterosalpingographic evaluation of 998 consecutive infertile women in Jos,
      Nigeria.

PMID- 20051276
TI  - Phase 1 safety and immunogenicity trial of the Plasmodium falciparum blood-stage
      malaria vaccine AMA1-C1/ISA 720 in Australian adults.
AB  - A Phase 1 trial was conducted in malaria-naive adults to evaluate the recombinant
      protein vaccine apical membrane antigen 1-Combination 1 (AMA1-C1) formulated in
      Montanide ISA 720 (SEPPIC, France), a water-in-oil adjuvant. Vaccinations were
      halted early due to a formulation issue unrelated to stability or potency. Twenty
      four subjects (12 in each group) were enrolled and received 5 or 20 microg
      protein at 0 and 3 months and four subjects were enrolled and received one
      vaccination of 80 microg protein. After first vaccination, nearly all subjects
      experienced mild to moderate local reactions and six experienced delayed local
      reactions occurring at Day 9 or later. After the second vaccination, three
      subjects experienced transient grade 3 (severe) local reactions; the remainder
      experienced grade 1 or 2 local reactions. All related systemic reactogenicity was
      grade 1 or 2, except one instance of grade 3 malaise. Anti-AMA1-C1 antibody
      responses were dose dependent and seen following each vaccination, with mean
      antibody levels 2-3 fold higher in the 20 microg group compared to the 5 microg
      group at most time points. In vitro growth-inhibitory activity was a function of
      the anti-AMA1 antibody titer. AMA1-C1 formulated in ISA 720 is immunogenic in
      malaria-naive Australian adults. It is reasonably tolerated, though some
      transient, severe, and late local reactions are seen.

PMID- 20051279
TI  - Triple A syndrome: a novel compound heterozygous mutation in the AAAS gene in an
      Italian patient without adrenal insufficiency.
AB  - Allgrove syndrome (or triple A syndrome) is a rare autosomal recessive disorder
      characterized by alacrima, achalasia, ACTH-resistant adrenal insufficiency and
      autonomic/neurological abnormalities. It is caused by mutations in the AAAS gene,
      located on chromosome 12q13. We describe a 42-year-old patient who presented with
      neuropathy and was found to have alacrima, achalasia, mild autonomic dysfunction
      with significant central and peripheral nervous system involvement. She was later
      diagnosed with oligosymptomatic triple A syndrome. Sequencing of the AAAS gene
      identified two heterozygous mutations within exon 14 and its donor splice site
      (p.L430F-c.1288C>T and c.1331+1G>T), one of which is novel. Allgrove syndrome
      should be suspected in patients with neurological impairment associated with two
      or more of the main symptoms (alacrima, achalasia or adrenal insufficiency).

PMID- 20051280
TI  - Metabolic signs of vitamin B(12) deficiency in humans: computational model and
      its implications for diagnostics.
AB  - Early diagnostics of cobalamin (Cbl, vitamin B(12)) deficiency is primarily based
      on measurements of the relevant metabolic markers in blood plasma--total B(12),
      specific Cbl-saturated transporter holo-transcobalamin (holoTC), and substrates
      of Cbl-dependent enzymatic reactions methylmalonic acid (MMA) and homocysteine
      (Hcy). Concentrations of B(12) and holoTC decrease whereas MMA and Hcy increase
      under deficiency. Yet, the results of individual tests are often contradictory
      and do not guarantee unambiguous diagnosis. The current work describes the
      metabolic manifestation of vitamin B(12) deficiency in terms of flux equations
      fitted to data sets from literature. The model mathematically connects all the
      markers and presents 4 independent measurements as a single point (x, y) in the
      combined coordinates x = (holoTC x B(12))((1/2)) and y = (1/2)log(10)(MMA x Hcy).
      Pairwise averaging compensates for the individual fluctuations of the markers
      caused by (1) irregular spikes of holoTC, (2) delayed change of the total plasma
      B(12) buffered by an internal Cbl depot, and (3) variations in the
      production/excretion velocities of MMA and Hcy. Bivariate distribution of the
      marker combinations (x, y) reveals several peaks of frequency in the analyzed
      mixed population. The peaks seem to represent the reference subgroups with
      different B(12) physiology and characteristic values of "wellness parameter": w =
      log(10)(holoTC(n)) + log(10)(B(12n)) - log(10)(MMA(n)) - log(10)(Hcy(n)), where
      concentrations are normalized (eg, MMA(n) = MMA/MMA(normal)). Dynamic response of
      the organism to B(12) intake is quantified and described as an additional
      analytical tool when classifying uncertain cases. The discussed mathematical
      approaches are of general applicability in diagnostics.

PMID- 20051281
TI  - Suppressed glucose metabolism in acinar cells might contribute to the development
      of exocrine pancreatic insufficiency in streptozotocin-induced diabetic mice.
AB  - High prevalence of exocrine pancreatic insufficiency has been observed in
      diabetic patients. However, the underlying mechanisms are not well known. Reduced
      cytosolic Ca(2+) signals in pancreatic acinar cells may contribute to lower
      digestive enzyme secretion. It is well known that adenosine triphosphate (ATP)
      regulates cytosolic Ca(2+) signals in acinar cells; however, little is known as
      to whether diabetes impairs glucose metabolism that produces ATP in acinar cells.
      Streptozotocin (STZ)-induced diabetic C57BL/6 mouse model was used. Four weeks
      after being diabetic, pancreatic acinar cells were isolated; and amylase
      secretion and contents, glucose utilization and oxidation, the activities of
      several key enzymes for glucose metabolism, and ATP and nicotinamide adenine
      dinucleotide phosphate (reduced form) (NADPH) contents were determined. Compared
      with controls, diabetic mice had lower body weight. Cholecystokinin-8- and
      acetylcholine-stimulated amylase secretion was significantly impaired, and total
      amylase activity in acinar cells of STZ-diabetic mice was markedly reduced.
      Glucose utilization and oxidation were suppressed; measured enzyme activities for
      glucose metabolism and the ATP and NADPH contents were significantly reduced.
      These data indicate that glucose metabolism and ATP and NADPH productions are
      very important for maintaining acinar cell normal function. Reduction of ATP
      (reduces cytosolic Ca(2+) signals) and NADPH (reduces cell capability for
      antioxidative stress) productions may contribute to the development of exocrine
      pancreatic insufficiency in STZ-diabetic mice.

PMID- 20051282
TI  - Differential impact of serum glucose, triglycerides, and high-density lipoprotein
      cholesterol on cardiovascular risk factor burden in nondiabetic, obese African
      American women: implications for the prevalence of metabolic syndrome.
AB  - Metabolic syndrome (MetS) as defined by the Adult Treatment Panel (ATP) III
      criteria includes 3 metabolic parameters: serum glucose, triglycerides, and high
      density lipoprotein cholesterol (HDL-C) measurements. However, the impact of each
      of the 3 metabolic parameters on cardiovascular disease (CVD) risk in African
      American women (AAW) is unknown. Therefore, we investigated CVD risk clusters
      associated with each of the 3 metabolic components of MetS in adult nondiabetic,
      overweight/obese AAW. We studied the clinical and metabolic CVD risk factors of
      258 AAW (mean age, 42.4 +/- 8.4 years; mean body mass index, 33.4 +/- 8.0
      (kg/m(2)). Fasting serum insulin, glucose, and C-peptide levels were obtained in
      each subject. Waist circumference and systolic and diastolic blood pressure were
      measured. Insulin sensitivity (Bergman minimal model method) and insulin
      resistance (homeostasis model assessment) were calculated. We examined the
      prevalence of MetS and its components associated with each of the 3 metabolic
      components (ie, serum glucose, HDL-C, and triglycerides) of the MetS as defined
      by ATP III. Worsening of any of the 3 metabolic parameters was associated with
      increasing waist circumference but not with age and body mass index nor with
      insulin, C-peptide, homeostasis model assessment of insulin resistance, and
      insulin sensitivity. As a group, the prevalence of MetS was 35.5% in our AAW. The
      prevalence of MetS increased 3-fold from first to third tertiles of serum glucose
      (14.1% and 42.3%, respectively). Worsening of serum HDL-C from tertiles 3 to 1
      was associated with significant increases in the prevalence of MetS (1.2% vs
      42.3%, respectively). Comparing first with third tertile of triglycerides, there
      was no significant increase in MetS in our AAW (7% vs 17%). Contrasting the 3
      metabolic components, the prevalence of MetS was higher in the third tertile of
      glucose (43.2%) and first tertile of HDL-C (42.3%) and least with the third
      tertile of triglycerides (17%). In summary, each of the metabolic components of
      MetS was associated with different degrees of the clustering of CVD risk factors
      in AAW. We found that alterations in serum glucose and HDL-C were more predictive
      of MetS, each yielding approximately 40% of the prevalence of MetS in our
      nondiabetic, obese AAW. We found that triglycerides had the least impact on MetS
      in our AAW. We propose (1) that the 3 metabolic parameters for MetS defined by
      ATP III should be weighted differently with respect to their potential for CVD
      risks and perhaps outcomes and (2) that nondiabetic AAW in our third tertile of
      serum glucose (>100 mg/dL) and/or first tertile of HDL-C (<40 mg/dL) should be
      targeted for screening for MetS.

PMID- 20051283
TI  - Complex mechanisms for the packaging of the UL16 tegument protein into herpes
      simplex virus.
AB  - The conserved UL16 tegument protein of herpes simplex virus exhibits dynamic
      capsid-binding properties with a release mechanism that is triggered during
      initial virus attachment events. In an effort to understand the capsid
      association and subsequent release of UL16, we sought to define the mechanism by
      which this protein is packaged into virions. The data presented here support a
      model for the addition of some UL16 to capsids prior to their arrival at the TGN.
      UL16 was found on capsids isolated from cells infected with viruses lacking UL36,
      UL37 or gE/gD, which are defective for budding and accumulate non-enveloped
      capsids in the cytoplasm. Additionally, membrane-flotation experiments showed
      that UL16 co-purified with cytoplasmic capsids that are not associated with
      membranes. Moreover, the amount of UL16 packaged into extracellular particles was
      severely reduced in the absence of two conserved binding partners, UL21 or UL11.

PMID- 20051284
TI  - The R306G and R506Q mutations in coagulation Factor V reveals additional cleavage
      sites for Activated Protein C in the R313-R321 region and at R505.
AB  - The procoagulant function of activated factor V (FVa) is inhibited by activated
      Protein C (APC) through proteolytic cleavages at R306, R506 and R679. Recombinant
      FVa mutated at all three APC-cleavage sites, FVa-GQA, was still inactivated by
      APC through at least two cleavages in the heavy chain of FVa; relatively rapid
      cleavage at R(x1) close to residue 506 and slower cleavage at R(x2) nearby
      residue 306. We investigated the exact location of these two cleavages, by
      substitution of arginines by glutamine within the R(x1)-region (R501, R505 or
      R510) and the R(x2)-region (R313, R316, R317 or R321). Immunoblot and kinetic
      analyses of the inactivation of activated R(x1)-mutants by APC revealed that
      using mutant FVa-GQA-505Q no R(x2)-R(x1) fragment was formed and that the
      inactivation reaction was first order with a rate constant of 1.0 x 10(4) M(-1)
      s(-1), similar to the rate constant of R(x2) cleavage (k(2)=1.3 x 10(4) M(-1) s(
      1)). No single arginine could be pinpointed identified as R(x2). Individual
      replacement of arginine by glutamine at positions 313, 316, 317 or 321 in FV-GQA
      505Q did not result in the disappearance of R(x2) as judged from kinetic and
      immunoblot analyses. However, replacement of all four arginines by glutamine
      completely prevented formation of the R(x2)-R(709) fragment. We conclude that
      substitution of arginine 506 by glutamine as in FV-Leiden, leads to the detection
      of a novel cleavage site at arginine 505 (R(x1)). Substitution of arginine 306 by
      glycine, like in FV-Cambridge, reveals several alternative cleavage sites near
      arginine 306, which together constitute a secondary cleavage site.

PMID- 20051285
TI  - The association of antiphospholipid antibodies with pregnancy-related first time
      venous thrombosis--a population-based case-control study.
AB  - In this population-based case-control study we explored the association of
      antiphospholipid antibodies with pregnancy-related venous thrombosis. From 1990
      through 2003 615 pregnant women were identified at 18 hospitals in Norway with a
      diagnosis of first time VT. In 2006, 531 of 559 eligible cases and 1092 of 1229
      eligible controls were invited for further investigations. The final study
      population comprised 313 cases and 353 controls, who completed a comprehensive
      questionnaire and donated a single blood sample, 3-16 years after index
      pregnancy. We report the results on lupus anticoagulant, anticardiolipin
      antibodies, and anti-ss(2) glycoprotein-1 antibodies alone, in combination, and
      with the contribution of the factor V Leiden and the prothrombin gene G20210A
      polymorphisms. Cut-off values for APAs were chosen according to current
      international consensus. 29 (9.3%) of the cases and 24 (6.8%) of the controls had
      at least one positive test for APAs (OR 1.4; 95% CI 0.8-2.5). Nine cases (2.8%)
      and no controls had more than one positive test (multi-positivity) for APAs.
      After excluding women with factor V Leiden or prothrombin polymorphisms, still 6
      cases were multi-positive for APAs. We conclude that multi-positivity, but not
      single-positivity, for APAs was weakly associated with a history of ante- and
      postnatal VT.

PMID- 20051286
TI  - Small intestinal bacterial overgrowth and warfarin dose requirement variability.
AB  - The dose of warfarin needed to obtain a therapeutic anticoagulation level varies
      widely among patients and can undergo abrupt changes for unknown reasons. Drug
      interactions and genetic factors may partially explain these differences.
      Intestinal flora produces vitamin K2 (VK2) and patients with small intestinal
      bacterial overgrowth (SIBO) rarely present reduced INR values due to insufficient
      dietary vitamin K. The present study was undertaken to investigate whether SIBO
      occurrence may affect warfarin dose requirements in anticoagulated patients.
      Based on their mean weekly dose of warfarin while on stable anticoagulation, 3
      groups of 10 patients each were defined: low dose (LD, <or=17.5 mg/wk of
      warfarin); high dose (HD, from 35-70 mg/wk); and very high dose (VHD>or=70
      mg/wk). Each patient underwent a lactulose breath test to diagnose SIBO. Plasma
      levels of warfarin and vitamin K-analogues were also assessed. Patients with an
      altered breath test were 50% in the VHD group, 10% in the HD group, and none in
      the LD group (P=0.01). Predisposing factors to SIBO were more frequent in the VHD
      group, while warfarin interfering variables were not. VHD patients were younger
      and had a higher plasma vitamin K1 (VK1) concentration (P>0.05). On the contrary,
      the plasma VK2 levels tended to be lower. This pilot study suggests that SIBO may
      increase a patient's warfarin dose requirement by increasing dietary VK1
      absorption through the potentially damaged intestinal mucosa rather than
      increasing intestinal VK2 biosynthesis. Larger studies are needed to confirm
      these preliminary data and to evaluate the effects of SIBO decontamination on
      warfarin dosage.

PMID- 20051287
TI  - Serum carbonic anhydrase IX during first-line therapy of ovarian cancer.
AB  - OBJECTIVE: Carbonic anhydrase IX (CAIX) is primarily involved in maintaining the
      extracellular pH. It is overexpressed in a variety of tumors including ovarian
      cancer. To evaluate the potential prognostic and predictive role of serum CAIX
      for therapy response in ovarian cancer, we analyzed longitudinal serum samples.
      METHODS: One hundred forty-eight serum samples from 37 patients with primary
      epithelial ovarian cancer were analyzed. Samples were prospectively collected at
      4 time points: (1) before radical surgery, (2) after surgery and before
      platinum/taxane chemotherapy, (3) during chemotherapy, and (4) after
      chemotherapy. Serum CAIX was quantified by ELISA and expression in tumor tissue
      was verified by immunohistochemistry. Correlation with response and clinical
      outcome as well as the tumor marker CA-125 was analyzed. RESULTS: Serum
      concentration of CAIX ranged between 30 and 1687 pg/mL and showed no significant
      changes during first-line therapy (median level before and after surgery 204 and
      198 pg/mL, during and after chemotherapy 175 and 181 pg/mL). There was no
      association between serum CAIX and progression-free or overall survival. CA-125
      decreased significantly after surgery (median serum level before and after
      surgery 413 and 84 kU/L, p<0.001) and further during and after first-line
      chemotherapy (median serum levels 21 and 15 kU/L, p<0.001). No intermarker
      correlation was observed. CONCLUSIONS: CAIX is upregulated in ovarian cancer and
      serum CAIX could be a marker to stratify patients for therapy response. However,
      CAIX serum levels did not change significantly during first-line therapy and were
      not prognostically relevant. Based on the findings of the current study, CAIX
      cannot be recommended for therapy monitoring in this context.

PMID- 20051288
TI  - Blood transfusion reduction with intravenous iron in gynecologic cancer patients
      receiving chemotherapy.
AB  - OBJECTIVE: To compare the incidence of repeated red blood cell (RBC) transfusion
      in anemic gynecologic cancer patients receiving platinum-based chemotherapy
      comparing intravenous and oral iron. MATERIALS AND METHODS: Forty-four anemic
      gynecologic cancer patients (hemoglobin level below 10 mg/dl) who required RBC
      transfusion were stratified and randomized according to baseline hemoglobin
      levels and chemotherapy regimen. Study group received 200 mg of intravenous iron
      sucrose and control group received oral ferrous sulphate 600 mg/day. RBC
      transfusion requirement in the consecutive cycle of chemotherapy was the primary
      outcome. Quality of life was evaluated by validated Thai version of the
      Functional Assessment of Cancer Therapy-Anemia (FACT-An). RESULTS: In a total of
      the 44 patients, there were 22 patients in each group. Five patients (22.7%) in
      the study group and 14 patients (63.6%) in the control group required RBC
      transfusion in consecutive cycle of chemotherapy (p=0.01). No significant
      difference in baseline hemoglobin and hematocrit levels was demonstrated in both
      groups. Significantly higher mean hemoglobin and hematocrit levels after
      treatment were reported in the study group (10.0+/-0.8 g/dl and 30.5+/-2.4%) than
      the control group (9.5+/-0.9 g/dl and 28.4+/-2.7%). No significant change of
      total FACT-An scores was noted between before and after treatment in both groups.
      No serious adverse events were reported and there was no significant difference
      among adverse events between both groups. CONCLUSION: Intravenous iron is an
      alternative treatment for anemic gynecologic cancer patients receiving platinum
      based chemotherapy and reduces the incidence of RBC transfusion without serious
      adverse events.

PMID- 20051289
TI  - Dangerous and severe personality disorder: An investigation of the construct.
AB  - Introduction of the construct "Dangerous and Severe Personality Disorder" (DSPD)
      by the UK Home Office and Department of Health has provoked strong debate and
      opposition. Its aims and that of proposed subsequent legislation was to enhance
      public protection by identifying and detaining a minority of persons with severe
      personality disorder who pose a high risk of serious sexual/violent offending.
      The most serious criticism was the ethical implication of allowing indefinite
      detention of people without criminal convictions. More recently, policy emphasis
      has shifted towards treatment. 1396 male prisoners serving sentences of 2+years
      for sexual/violent offenses were prospectively interviewed (personality
      disorders, psychopathy, and risk) at a mean follow-up of 2 years. The prevalence
      of DSPD was 15%. Significantly more re-offended. Five DSPD offenders would need
      treatment to prevent one violent act. Based on an estimate of attributable risk,
      successful treatment of DSPD could reduce violent re-convictions among DSPD
      offenders by 71% and violent/sexual re-offenses in the prison population by 27%.
      DSPD criteria correctly identify high risk prisoners but primarily through risk
      related demographic features. DSPD does not accurately identify serious
      sexual/violent re-offenders. The DSPD programme may reduce major violent re
      offending if treatment interventions prove effective.

PMID- 20051290
TI  - Biosorption and bioaccumulation--the prospects for practical applications.
AB  - The paper summarizes the present and future course of biosorption and
      bioaccumulation, as the branch of science, pointing out on their basic
      assumptions, philosophy and the goals. The processes are presented as new tools
      for separation technologies of XXI century. The paper is the discussion with the
      literature on the future prospects of those processes, pointing out that research
      should be oriented on the practical applications, in order to make technologies
      from the processes and also discusses other than environmental possible future
      applications. It presents an own point of view on these techniques, after some
      years of working in this very area. Biosorption and bioaccumulation, involve
      interactions and concentration of toxic metals or organic pollutants (e.g. dyes)
      in the biomass, either living (bioaccumulation) or non-living (biosorption). The
      processes play an important role in natural cycling of matter in the environment.
      The paper discusses the possibilities which offer research on pollutants-biomass
      interactions, pointing out that the key to elaborate an efficient method working
      for the nature would be to understand the mechanisms governing the processes,
      parameters which influence both equilibrium and kinetics, through the observation
      of naturally occurring phenomena. Only then we would be able to control and carry
      out under industrial regime, so the processes would work beneficially for the
      environment.

PMID- 20051291
TI  - Gender differences in clinical characteristics in a naturalistic sample of
      depressive outpatients: the Leiden Routine Outcome Monitoring Study.
AB  - BACKGROUND: No previous large scale studies have assessed gender differences in
      naturalistic samples of major depressive disorder (MDD) outpatients. We therefore
      determined gender differences in comorbidity, symptom patterns and subjective
      health status in these outpatients in a mental healthcare setting. METHODS: Of
      3798 consecutive adult patients (age range: 18-65), 1131 (65.1% women) fulfilled
      DSM-IV criteria of current MDD on the Mini-International Neuropsychiatric
      Interview (MINI-Plus). Patients were routinely assessed with Routine Outcome
      Monitoring (ROM), including the Montgomery-Asberg Depression Rating Scale
      (MADRS), Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI) and
      Short Form-36 (SF-36). RESULTS: No gender differences were found in disease
      severity using the clinician-rated MADRS. However, women showed a significant
      higher depression severity measured with the self-report BDI-II. Also,
      psychopathological symptoms self-reported with the BSI were higher, and reported
      health status on the SF-36 was lower in women. In men with MDD, social phobia,
      attention deficit hyperactivity disorder, and alcohol and drug misconduct were
      more common comorbid disorders, while in women with MDD posttraumatic stress
      disorder and bulimia nervosa were more common, as well as atypical features of
      depression. LIMITATIONS: The use of retrospective reports of lifetime
      psychopathology might have led to recall bias. 20% of subjects were excluded from
      ROM due to language problems or logistical reasons. CONCLUSIONS: Although women
      self-reported higher depression severity, more severe general psychopathological
      symptoms and lower health status, no differences in disease severity were found
      on interviewer ratings. These findings could have implications for clinical
      decision making and treatment.

PMID- 20051293
TI  - Takotsubo cardiomyopathy--the current state of knowledge.
AB  - Takotsubo cardiomyopathy is defined as acute chest pain during stressful
      incidents which is associated with ST-segment abnormalities and/or increased
      serum troponin levels. There is also regressive systolic dysfunction which is
      usually localized in the apical and medial left ventricles but there are no
      significant coronary artery lesions. The ventricular asynergy is also described
      in the right ventricle but is less common. Almost all the patients are women. The
      onset of this disease is typically triggered by an acute emotional or stress
      event or by an accumulation of trivial and repetitive stresses. The etiology of
      this syndrome remains unclear. Myocardial ischemia and reperfusion due to
      microvascular spasm, aborted myocardial infarction and related no-reflow
      phenomenon have been proposed as inducers of Takotsubo cardiomyopathy. The
      temporal relationship between the stressful event and the triggering of the
      clinical syndrome as well as the report of elevated catecholamine plasma levels
      during the acute phase suggest a possible involvement of the sympathetic nervous
      system. A smaller left ventricular size and hormonal disturbances in women may
      also play a role.

PMID- 20051292
TI  - Prenatal beta-endorphin as an early predictor of postpartum depressive symptoms
      in euthymic women.
AB  - BACKGROUND: After delivery, many women experience symptoms of postpartum
      depression (PPD), and early identification of women at risk is therefore
      important. The opioid peptide beta-endorphin has been implicated in non-puerperal
      depression but its role in the development of PPD is unknown. METHODS: Three
      hundred and seven women with a singleton, full-term (>37.0 weeks' GA) pregnancy
      were recruited early in pregnancy and followed up into the postpartum period.
      Blood samples were obtained at 15, 19, 25, 31 and 37 weeks' gestational age (GA)
      and at 9 weeks postpartum for assessment of beta-endorphin. Depressive symptoms
      were assessed with the Center for Epidemiological Studies-Depression scale at the
      last four pregnancy visits and with the Edinburgh Postnatal Depression Scale
      postpartum. RESULTS: Among women who were euthymic at 25 weeks' GA, those who
      proceeded to develop PPD symptoms had higher levels of beta-endorphin throughout
      pregnancy compared to women without PPD symptoms (all t>2.11, p<.05). At each
      assessment, women above the cut-off score for beta-endorphin were at more than
      three-fold risk for PPD symptoms (odds ratios 3.19-4.68) compared to women below
      the cut-off score. LIMITATIONS: Self-report of depressive symptoms, no mental
      health history. CONCLUSIONS: Beta-endorphin may be a useful early predictor of
      PPD symptoms in women who do not report depressive symptoms in mid-pregnancy. If
      replicated, these findings have clinical implications for the identification and
      treatment of this at-risk group and further suggest that some of the pathways
      leading to this complex disorder may be specific to subgroups of women.

PMID- 20051294
TI  - High serum level of neopterin is a risk factor of patients with heart failure.
AB  - Serum neopterin concentration was measured in 198 patients with chronic heart
      failure (CHF) and 62 control subjects by ELISA. Patients were prospectively
      followed during a median follow-up period of 745 days with end points of cardiac
      death or re-hospitalization due to progressive heart failure. Serum concentration
      of neopterin increased with advancing New York Heart Association (NYHA)
      functional class (P<0.001). High neopterin group had a significantly higher
      incidence of cardiac events than low neopterin group (P<0.0001). In the
      multivariate Cox analysis, serum neopterin concentration was an independent risk
      factor for cardiac events (hazard ratio 1.70, 95%CI 1.16-2.50, P=0.0068). Serum
      neopterin concentration is a novel prognostic marker for CHF.

PMID- 20051296
TI  - Definitive diagnosis of Hashitoxicosis with pericardial effusion.

PMID- 20051295
TI  - Influence of age on pain perception in acute myocardial ischemia: a possible
      cause for delayed treatment in elderly patients.
AB  - BACKGROUND: Elderly patients tend to seek later for medical help during
      myocardial infarction. This may be caused by impaired pain perception with
      ageing. The aim of our study was to prospectively evaluate age-dependent
      differences in pain perception during temporary induced coronary ischemia.
      METHODS: In 102 patients (68 male, age 68+/-11 years) undergoing percutaneous
      coronary intervention, ischemia was induced by balloon inflation for up to 120 s.
      Time to onset of perceived pain, pain characteristics and pain severity (0=no
      pain, 100=worst pain possible) was registered. This was repeated twice to
      evaluate ischemic preconditioning. A 12 lead ECG-tracing was simultaneously
      recorded. Patients were divided by their median age into 2 groups with comparable
      demographics: <=69 years (group 1) and >69 years (group 2). RESULTS: Group 1
      patients demonstrated earlier onset of pain (most apparent during the second
      inflation: 31+/-15 s vs. 46+/-26 s; p<0.001), and greater pain severity
      (inflation #1: 64+/-21 vs. 51+/-25 [p=0.017]; #2: 66+/-23 vs.52+/-27 [p=0.008];
      #3: 63+/-23 vs. 54+/-24 [p=0.085]). ST-changes did not differ (0.24+/-0.10 vs.
      0.20+/-0.14, [p=0.18]; 0.27+/-0.17 vs. 0.20+/-0.14, [p=0.11]; 0.19+/-0.13 vs.
      0.16+/-0.09; [p=0.32]). Time from occlusion to onset of ECG changes did not
      differ between the groups, but increased with repetitive inflations (inflation
      #1: 29+/-11 s vs. 29+/-11 s; #2: 31+/-14 vs. 33+/-11; #3: 39+/-21 vs. 40+/-15 s
      [increase p=0.017; p<0.001]). CONCLUSION: These data suggest that the perception
      of pain from myocardial ischemia in the elderly is significantly less severe and
      delayed compared to younger patients.

PMID- 20051297
TI  - Bisphosphonate use in women and the risk of atrial fibrillation: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Bisphosphonates are used for the prevention and treatment of
      osteoporosis, but there have been concerns about a potential link between
      bisphosphonate therapy and atrial fibrillation. Data on the effects of
      bisphosphonate on the risk of atrial fibrillation are conflicting and the
      association of serious atrial fibrillation (defined as events resulting in
      hospitalization or disability or judged to be life-threatening) with the use of
      bisphosphonates is uncertain. HYPOTHESIS: We aimed to systematically evaluate the
      association of bisphosphonate use with the risk of atrial fibrillation. METHODS:
      We performed a systematic literature search for clinical trials using
      bisphosphonates and providing data on the outcome of atrial fibrillation. Four
      randomized controlled trials and 3 population based case-control studies were
      included in the final analysis. A meta-analysis was performed with the 4
      randomized controlled trials to determine the risk of serious atrial
      fibrillation. RESULTS: For the purpose of meta-analysis, the studies were
      homogenous; therefore the Mantel-Haenszel fixed-effect model was used to
      calculate combined relative risk (RR). A two-sided alpha error of less than 0.05
      was considered to be statistically significant (p<0.05). Four studies with 26126
      postmenopausal women were included in the meta-analysis. Meta-analysis revealed
      that serious atrial fibrillation occurred more frequently in the bisphosphonate
      group compared to the placebo group (RR 1.525; 95% CI, 1.166 to 1.997; p=0.002).
      Two out of 3 observational studies indicated a statistically significant increase
      in the risk of atrial fibrillation with bisphosphonate therapy. CONCLUSIONS:
      Bisphosphonate use is associated with a significant increase in the risk of
      serious atrial fibrillation in postmenopausal women.

PMID- 20051298
TI  - In vivo inhibitory effect of anti-muscarinic autoantibodies on the
      parasympathetic function in Chagas disease.

PMID- 20051299
TI  - Safety and efficacy of SITAgliptin plus GRanulocyte-colony-stimulating factor in
      patients suffering from Acute Myocardial Infarction (SITAGRAMI-Trial)--rationale,
      design and first interim analysis.
AB  - AIMS: Our pre-clinical studies demonstrated that G-CSF based stem cell
      mobilization in combination with genetic or pharmaceutical CD26/DPP-IV inhibition
      after acute myocardial infarction leads to improved cardiac homing of stem cells,
      enhanced heart function and increased survival. Thereupon, we initiated a phase
      III, multi-centre, randomised, placebo-controlled efficacy and safety study
      (n=100) analyzing the effect of combined application of G-CSF and Sitagliptin,
      which is a clinically admitted, anti-diabetic DPP-IV-inhibitor, after acute
      myocardial infarction ("SITAGRAMI-Trial"; EudraCT Number: 2007-003941-34).
      METHODS: The primary objective of the study is to assess myocardial regeneration
      by improved myocardial homing of mobilized stem cells, as measured by cardiac
      function using MRI analysis. In this paper, we report on the study design and a
      planned first interim-analysis on safety issues without unblinding. RESULTS:
      During the first 6 weeks of follow-up, only two major adverse cardiac events
      occurred (one de novo stenosis and one instent-restenosis) in the first 36
      patients. Presumably, they were not related to any study medication. No other
      side effects like headache, bone pain, hypoglycaemias etc. were observed.
      Furthermore, no myocardial infarction or death occurred in any patient. Thus, the
      rate of serious adverse events lay within the expected range. CONCLUSIONS: Our
      data demonstrate that the combined application of Sitagliptin and G-CSF seems to
      be safe on the short term and feasible after acute myocardial infarction and may
      represent a new therapeutic option in future.

PMID- 20051300
TI  - Long-term outcome after drug-eluting stents implantation: target lesion versus
      nontarget lesion repeated intervention.
AB  - We sought to investigate the relative clinical significance of target and
      nontarget lesions repeated percutaneous coronary intervention (re-PCI) in
      patients implanted with drug-eluting stents (DES). Out of 2626 consecutive DES
      patients, we retrospectively selected 166 (6.3%; 123 males, aged 65+/-10 years)
      who had a clinically-driven re-PCI over a mean follow-up of 15 months. Seventy
      five patients (45%) underwent the second procedure for disease progression in
      nontarget lesions (nontarget lesion re-PCI group) while 91 (55%) showed target
      lesion in-stent restenosis or thrombosis (target lesion re-PCI group), with no
      significant intergroup difference in the temporal trends of re-PCI. The
      prevalence of stable coronary artery disease and acute coronary syndromes (ACS)
      was 22% and 78% in the target lesion re-PCI vs. 81% and 19% in the nontarget
      lesion re-PCI group (overall p<0.001), respectively. In-stent restenosis
      accounted for 75% of second procedures in the target lesion re-PCI group and
      presented as an ACS in 72% of cases. The need for a new PCI in DES patients is
      relatively low in a real world setting. Stent-related events in the target lesion
      and progression of disease in nontarget lesions account to a similar extent for
      re-PCI, although their clinical presentation is strikingly different. The most
      common presentation of events related to previously treated lesions is an
      unstable syndrome, which provides support to the concept that also restenosis in
      a DES should not be considered a clinically benign entity.

PMID- 20051301
TI  - Partial avulsion of prosthetic aortic valve caused by S. epidermidis infection
      resulting in a giant false aneurysm of the complete thoracic aorta.
AB  - A 69-year-old man was presented with a holosystolic and early diastolic murmur in
      cardiac auscultation, pretibial edema and elevated inflammation markers. Aortic
      valve and ascending aorta had been replaced 9 months earlier. Transesophageal
      echocardiography revealed massive eccentric regurgitation and dehiscence of the
      aortic valve, resulting in a giant circular false aneurysm with connection to the
      lumen of the aortic arch. CT and MR confirmed extensive leakage in a covered
      perforation. The false lumen was confined by a newly formed vessel wall, since
      the native Aorta ascendens had been excised. Smooth muscle cells expressing the
      progenitor marker CD34 were detected selectively in this region, indicating a
      contribution of circulating progenitor cells to the false vessel wall. After
      detection of Staphylococcus epidermidis in blood, another urgent Bentall
      operation was performed. However, the patient succumbed to right ventricular
      failure and multiple organ failure on postoperative day 1.

PMID- 20051302
TI  - QRS complex abnormalities in subjects with idiopathic ventricular fibrillation.
AB  - Recent data point to a high incidence of early repolarization abnormalities among
      patients with idiopathic ventricular fibrillation (IVF). ECG data from 11
      patients with idiopathic IVF were evaluated for the presence of initial (slurring
      or notching of the ascending limb of the R-wave that resembles a "pseudo" delta
      wave) and terminal (slurring or notching of the descending limb of the R-wave
      resembling the early repolarization pattern) QRS complex abnormalities in at
      least two contiguous leads. The control group comprised 101 age- and gender
      matched healthy individuals without structural heart disease in whom the presence
      of an accessory pathway was excluded during electrophysiological study. Initial
      QRS complex abnormalities in the setting of a normal PR interval were more
      frequent in subjects with IVF than in control population (36.4% vs. 8.9%,
      p=0.023). Although not statistically significant, an early repolarization pattern
      was also more common among patients with IVF (27.3% vs. 12.9%, p=0.192). Among
      patients with IVF, there is an increased prevalence of initial and terminal QRS
      complex abnormalities.

PMID- 20051303
TI  - Comparison of invasiveness among surface-adherent variants of Listeria
      monocytogenes in Caco-2 cell culture assays.
AB  - The persistence of Listeria monocytogenes in meat processing plants is believed
      to be partly linked with their adherence properties to abiotic surfaces that may
      allow contamination of ready-to-eat (RTE) foods. Isolates of raw meats, RTE meats
      and environmental samples from RTE meat processing facilities that demonstrated
      differences in adherence to abiotic surfaces (glass, plastic, stainless steel,
      and rubber) were tested for cellular adherence and invasion in the Caco-2 human
      cell line. Strains of L. monocytogenes were classified into strong (CW50, 99-38,
      CW77, SM5 and CW62) and weakly adherent (CW34, CW35, CW72, SM3, J7 and J126)
      based on a microplate adherence assay using the fluorescing substrate, 5,6-CFDA.
      These strains were tested for adherence and invasion in cell culture assays with
      Caco-2 cells. At long incubation time (2h) and high multiplicity of infection
      (MOI, 100:1) we observed equivalent cellular adherence and invasiveness. After
      optimizing conditions for time of infection (15-, 30-, 60-, 90-, and 120-min) and
      MOI (100:1, 10:1, 1:1, and 0.1:1), we found that under the conditions of 15-min
      infection time at an MOI of 10:1 (Listeria:Caco-2 cells), we again observed
      equivalent cellular adherence by the two distinct surface-adherent groups, but we
      only recovered invading Listeria from the group that was strongly adherent to
      environmental surfaces. The data indicate that a surface factor that provides for
      strong environmental surface adherence may also be involved with internal
      cellular virulence and survival and implicates strongly adherent strains as
      possibly being of greater invasiveness than weakly adherent strains.

PMID- 20051304
TI  - Inhibition by pectic oligosaccharides of the invasion of undifferentiated and
      differentiated Caco-2 cells by Campylobacter jejuni.
AB  - The ability of pectic oligosaccharides (POS) to inhibit adherence to and invasion
      of undifferentiated (UC) and differentiated (DC) Caco-2 cells by Campylobacter
      jejuni (C. jejuni) was investigated. It was observed that both adherence and
      invasion were significantly higher in UC than in DC. POS (2.5mg/ml) had no
      significant effect on the number of bacteria which can adhere to cells, but they
      significantly inhibited cell invasion. The extent of the anti-invasive effect of
      POS was dependent on the concentration, although the entire range tested (from
      2.5mg/ml to 0.05 mg/ml) was capable of inhibiting the invasion of Caco-2 cells by
      Campylobacter to some degree. The pre-incubation or not of C jejuni with POS did
      not influence the behaviour observed. The results obtained in this work suggest
      that POS could be potentially useful as alternatives to antibiotics in the
      control of C. jejuni.

PMID- 20051305
TI  - Genetic analyses of the antibiotic resistance of Bifidobacterium bifidum strain
      Yakult YIT 4007.
AB  - Bifidobacterium bifidum strain Yakult YIT 4007 (abbreviated as B. bifidum YIT
      4007) is a commercial strain and resistant to erythromycin, neomycin, and
      streptomycin. Resistances to these antibiotics were endowed by sequential
      isolation of resistant mutants from its susceptible progenitor strain YIT 4001.
      Comparison of nucleotide sequences of various candidate genes of both strains led
      us to find that B. bifidum YIT 4007 had mutations on three copies of 23S
      ribosomal RNA genes, an 8 bp deletion of the rluD gene for pseudouridine
      synthase, and a mutation on the rpsL gene for ribosomal protein S12. The
      responsibility of these mutations to antibiotic resistances was supported by
      analyses of newly isolated mutants resistant to these antibiotics. The antibiotic
      resistances of B. bifidum YIT 4007 were evidently acquired by mutations of the
      structural genes on the chromosome and not associated with mobile genetic
      elements like insertion sequences, phages, and plasmids.

PMID- 20051306
TI  - Selection of autochthonous Oenococcus oeni strains according to their oenological
      properties and vinification results.
AB  - The goal of this study is to carry out a characterization of 84 Oenococcus oeni
      strains isolated from Tempranillo wine samples taken at the cellars in Castilla
      La Mancha, in order to select those showing the highest potential as oenological
      starter cultures. Various oenological properties were analyzed and the ability of
      some of these strains to grow and undergo MLF in simulated laboratory
      microvinifications was tested. Twenty-two strains were selected on the basis of
      fermentation assays and the eight that produced the best results in the chemical
      analysis of the wines were chosen for further assays. None of the eight strains
      was either able to produce biogenic amines or displayed tannase or anthocyanase
      activities. On the other hand all presented activity against p-NP-beta
      Glucopyranoside, p-NP-alpha Glucopyranoside and p-NP-beta xylopyranoside.
      Randomly Amplified Polymorphic DNA (RAPD)-PCR was used to determine the
      colonizing ability of the inoculated strains. C22L9 and D13L13 strains showed the
      highest implantation values. On the basis of this characterization, two strains
      have been selected which are suitable as starter cultures for MLF of Tempranillo
      wine. Use of these strains will ensure that MLF proceeds successfully and gives
      retention of the organoleptic characteristics of wines made in Castilla-La
      Mancha.

PMID- 20051307
TI  - Role of RpoS in the susceptibility of low salinity-adapted Vibrio vulnificus to
      environmental stresses.
AB  - Vibrio vulnificus is an opportunistic pathogen commonly found in oyster and
      marine environments, which frequently encounters low salinity stress in its
      natural and food processing environment. In this study, the responses of a V.
      vulnificus wild-type strain C78140o and its rpoS isogenic mutant AH1 to sublethal
      low salinity were examined to investigate the role of rpoS in this response. Both
      strains, adapted in low salinity (0.4% NaCl), were protected against the lethal
      low salinity (0.1% NaCl), but were not protected against heat (45 degrees C) or
      acid stress (pH 3.5), and were sensitized against 5% bile. Protection of the
      adapted cells against the lethal low salinity was not inhibited by the addition
      of chloramphenicol. Hemolysis was detected only in the adapted C78140o cells and
      its spent medium, and was inhibited by chloramphenicol. Transcription of the
      mechanosensitive channels (VVl_1542 and VVl_2579) and an aquaporin gene
      (VVl_2010) was markedly increased in the wild-type cells adapted in low salinity
      medium, while transcription of these genes was slightly enhanced or inhibited in
      AH1 cells. Results of this study support the active role of rpoS in the low
      salinity adaptation of V. vulnificus by regulating the expression of virulence
      and low salinity-associated factors, although rpoS is not related to the
      immediate protection of the adapted cells against lethal low salinity.

PMID- 20051308
TI  - Enhanced antimicrobial activity of starch-based film impregnated with thermally
      processed tannic acid, a strong antioxidant.
AB  - Starch-based films impregnated with fresh tannic acid (FTA/starch film) and
      thermally processed tannic acid (PTA/starch film) were assessed for inhibition of
      Escherichia coli O157:H7 and Listeria monocytogenes. Disc-diffusion assay
      revealed that the PTA/starch film showed larger clear zone around the film on the
      bacterial lawn than the FTA/starch film at the same tannic acid concentrations
      (0.45 to 4.5mg per disc). Viable cell count assays in tryptic soy broth showed
      that the PTA/starch film also had a stronger antimicrobial activity on these
      foodborne pathogens than the FTA/starch film. L. monocytogenes did not replicate
      in trypic soy broth containing the FTA/starch film for the first 8h but
      multiplied up to 9.22 log CFU/ml at 48 h of incubation. The PTA/starch film
      caused a 2.72-log decrease in L. monocytogenes cells over the same time period.
      While 5-log E. coli O157:H7 cells were inactivated by the FTA/starch film within
      48 h, more than 7-log E. coli O157:H7 cells were killed by the PTA/starch film
      over the same period. The antimicrobial activity of FTA/starch and PTA/starch
      film was primarily pH independent. HPLC measurement of the FTA or PTA release
      from starch film in water revealed that their release kinetic curves were in well
      match with their inactivation curves for E. coli O157:H7 and L. monocytogenes in
      0.1% peptone water. In addition to antimicrobial activity, FTA showed antioxidant
      activity on soybean oil by doubling the induction time of oil oxidation. PTA
      further enhanced the oxidative stability of the oil by 17%. These results
      suggested that the use of processed tannic acid in starch films could improve the
      safety and quality of foods.

PMID- 20051309
TI  - Overcoming the fear of lethal injury: evaluating suicidal behavior in the
      military through the lens of the Interpersonal-Psychological Theory of Suicide.
AB  - Suicide rates have been increasing in military personnel since the start of
      Operation Enduring Freedom and Operation Iraqi Freedom, and it is vital that
      efforts be made to advance suicide risk assessment techniques and treatment for
      members of the military who may be experiencing suicidal symptoms. One potential
      way to advance the understanding of suicide in the military is through the use of
      the Interpersonal-Psychological Theory of Suicide. This theory proposes that
      three necessary factors are needed to complete suicide: feelings that one does
      not belong with other people, feelings that one is a burden on others or society,
      and an acquired capability to overcome the fear and pain associated with suicide.
      This review analyzes the various ways that military service may influence
      suicidal behavior and integrates these findings into an overall framework with
      relevant practical implications. Findings suggest that although there are many
      important factors in military suicide, the acquired capability may be the most
      impacted by military experience because combat exposure and training may cause
      habituation to fear of painful experiences, including suicide. Future research
      directions, ways to enhance risk assessment, and treatment implications are also
      discussed.

PMID- 20051311
TI  - Social network effects in alcohol consumption among adolescents.
AB  - In this paper we seek to empirically quantify the role of peer social networks in
      explaining drinking behavior among adolescents. Using data from a nationally
      representative sample of adolescents we utilize a multivariate structural model
      with school-level fixed effects to account for the problems of contextual
      effects, correlated effects and peer selection to purge the potential biases from
      the estimates of peer influence. Our peer group measures are drawn not only from
      the nomination of close friends, but also from classmates. Drinking behavior
      among the peer groups was constructed using the peers' own report of their
      alcohol consumption. Controlling for parent level characteristics, and other
      demographic parameters, we find that a 10% increase in the proportion of
      classmates who drink will increase the likelihood of drinking participation and
      frequency by approximately four percentage points. We also find evidence to show
      that the influence of close friends, while still significant, diminishes in
      magnitude after accounting for unobserved environmental confounders. Our findings
      support the literature that peer effects are important determinants of drinking
      behavior even after controlling for potential biases. Effective policy aimed at
      reducing alcohol consumption among adolescents would consider these significant
      peer effects.

PMID- 20051310
TI  - Do all psychological treatments really work the same in posttraumatic stress
      disorder?
AB  - A recent meta-analysis by Benish, Imel, and Wampold (2008, Clinical Psychology
      Review, 28, 746-758) concluded that all bona fide treatments are equally
      effective in posttraumatic stress disorder (PTSD). In contrast, seven other meta
      analyses or systematic reviews concluded that there is good evidence that trauma
      focused psychological treatments (trauma-focused cognitive behavior therapy and
      eye movement desensitization and reprocessing) are effective in PTSD; but that
      treatments that do not focus on the patients' trauma memories or their meanings
      are either less effective or not yet sufficiently studied. International
      treatment guidelines therefore recommend trauma-focused psychological treatments
      as first-line treatments for PTSD. We examine possible reasons for the discrepant
      conclusions and argue that (1) the selection procedure of the available evidence
      used in Benish et al.'s (2008)meta-analysis introduces bias, and (2) the analysis
      and conclusions fail to take into account the need to demonstrate that treatments
      for PTSD are more effective than natural recovery. Furthermore, significant
      increases in effect sizes of trauma-focused cognitive behavior therapies over the
      past two decades contradict the conclusion that content of treatment does not
      matter. To advance understanding of the optimal treatment for PTSD, we recommend
      further research into the active mechanisms of therapeutic change, including
      treatment elements commonly considered to be non-specific. We also recommend
      transparency in reporting exclusions in meta-analyses and suggest that bona fide
      treatments should be defined on empirical and theoretical grounds rather than by
      judgments of the investigators' intent.

PMID- 20051312
TI  - Cortisol in the first year of life: normative values and intra-individual
      variability.
AB  - INTRODUCTION: Many studies have incorporated cortisol measurements when studying
      infant development, but descriptions of normal development of basal cortisol
      levels in large study populations are scarce. The present study aimed to
      establish norm values for infant basal cortisol levels and to examine the
      development of intra-individual variability in the first year of life. METHODS:
      More than 2500 cortisol samples were collected in 300 infants at three different
      ages. At each age four 1100h samples were collected to determine average cortisol
      levels and intra-individual variability. The development of basal cortisol levels
      and intra-individual variability was analyzed with multilevel growth curve
      modeling. RESULTS: Norm tables with 90 and 95% intervals are presented. Basal
      cortisol levels decreased gradually over the year. Intra-individual variability
      was relatively large and stable in the first half year but decreased towards the
      end of the year. CONCLUSIONS: The results of this study will aid researchers in
      evaluating cortisol data collected in early infancy. It also underscores the
      importance of taking intra-individual cortisol variability into account in
      studies involving infants.

PMID- 20051313
TI  - Antibodies to measles in individuals with recent onset psychosis.
AB  - BACKGROUND: Measles virus is a highly prevalent neurotropic virus capable of
      causing persistent infections within the central nervous system. METHODS: We
      measured IgG class antibodies to measles in 820 individuals including 138 with
      recent onset psychosis, 378 with persistent schizophrenia, and 304 non
      psychiatric controls. Levels of antibodies among the groups were compared by
      bivariate and by multivariate analyses and correlated with clinical and
      demographic variables. RESULTS: The level of measles antibodies in individuals
      with a recent onset of psychosis was greater than the level of antibodies in
      individuals with persistent schizophrenia or individuals without a history of a
      psychiatric disorder (p<.00001). The level of measles antibodies in the
      individuals with persistent schizophrenia was greater than the level of measles
      antibodies in the controls (p<.001). Recent onset of psychosis was associated
      with having elevated levels of measles antibodies, defined as the 90th percentile
      of the levels of the controls, with an odds ratio of 8.0 (95% CI 4.6, 14.0);
      persistent schizophrenia was associated with having this level with an odds ratio
      of 2.3 (95% CI 1.4, 3.7). Within the psychiatric groups, measles antibody levels
      were associated with age, race, and current treatment with the antipsychotic
      medication, olanzapine. CONCLUSIONS: The reasons for elevated levels of measles
      antibodies in the psychiatric groups are not known with certainty and should be
      studied in prospective investigations.

PMID- 20051315
TI  - Reasons for smoking among individuals with schizophrenia.

PMID- 20051314
TI  - Emotional experience predicts social adjustment independent of neurocognition and
      social cognition in schizophrenia.
AB  - BACKGROUND: Emotional abnormalities are prominent features of schizophrenia.
      While the capacity for emotions is essential to social adaptation, little is
      known about the role of emotional experience in the social dysfunction observed
      in schizophrenia. OBJECTIVE: This study examined the contribution of emotional
      experience, neurocognition, and social cognition to functional outcome in
      schizophrenia. METHOD: Self-reported emotional experience (anhedonia, affect
      intensity, and emotion frequency) was assessed in 33 stable
      schizophrenic/schizoaffective patients and 33 healthy controls. Symptoms,
      neurocognition, social cognition, and functional outcome were also assessed.
      RESULTS: Patients and controls exhibited good internal reliability on all self
      report scales, except for negative affect intensity. Patients reported equally
      intense but less frequent positive emotions, more intense and frequent negative
      emotions, and more anhedonia. Results of hierarchical regression analyses showed
      that emotional experience accounted for significant amounts of variance of social
      adjustment independent of neurocognition and social cognition. CONCLUSION: These
      data show that emotional experience can be reliably assessed and is an important
      determinant of functional outcome in schizophrenia.

PMID- 20051316
TI  - A follow-up MRI study of the superior temporal subregions in schizotypal disorder
      and first-episode schizophrenia.
AB  - While longitudinal magnetic resonance imaging (MRI) studies have demonstrated
      progressive gray matter reduction of the superior temporal gyrus (STG) during the
      early phases of schizophrenia, it remains unknown whether patients with
      schizotypal features exhibit similar STG changes. In this study, longitudinal MRI
      data were obtained from 18 patients with first-episode schizophrenia, 13 patients
      with schizotypal disorder, and 20 healthy controls. The volumes of the STG and
      its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT),
      rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7
      years) scans and were compared across groups. At the baseline, both the
      schizophrenia and schizotypal patients had smaller left PT and left caudal STG
      than the controls. In a longitudinal comparison, the schizophrenia patients
      showed significant gray matter reduction of the STG over time (left: -2.8%/year;
      right: -1.5%/year) compared with the schizotypal patients (left: -0.6%/year;
      right: -0.3%/year) and controls (left: 0.0%/year; right: -0.1%/year) without a
      prominent effect of subregion or type of antipsychotic (typical/atypical). In the
      schizophrenia patients, greater annual volume reductions of the left PP and right
      PT were correlated with less improvement of positive psychotic symptoms. A higher
      cumulative dose of antipsychotics during follow-up in schizophrenia was
      significantly correlated with less severe gray matter reductions in the left PT
      and bilateral caudal STG. Our findings suggest that the left posterior STG
      subregions are commonly reduced in diseases of the schizophrenia spectrum;
      whereas, schizophrenia patients exhibit further progressive STG changes
      associated with overt psychosis in the early years of the illness.

PMID- 20051317
TI  - The chitinase 3-like 1 gene and schizophrenia: evidence from a multi-center case
      control study and meta-analysis.
AB  - The chitinase 3-like 1 (CHI3L1) gene acts as a cellular survival factor in
      response to several environmental and psychosocial stresses. The expression level
      of CHI3L1 was increased in the hippocampus and prefrontal cortex regions of
      patients with schizophrenia. Genetic variants of the CHI3L1 gene have been
      significantly associated with schizophrenia in two distinct ethnic groups, the
      Chinese and Irish populations. The aims of this study are to confirm the
      association between the CHI3L1 gene and schizophrenia in a Japanese population
      using the largest sample size to date (1463 cases and 1795 controls) and perform
      a meta-analysis of the combined samples (3005 cases, 3825 controls and 601
      trios). We found significant associations between single nucleotide polymorphism
      (SNP) 4/rs4950928 (p=0.009), which is located in the promoter region of the
      CHI3L1 gene, and haplotypes including this SNP and schizophrenia (the most
      significant global p<0.001). As the meta-analysis of the combined samples showed
      significant heterogeneity among studies of SNP3/rs10399805 (p=0.026) and SNP4
      (p<0.001), we performed meta-analyses separately in the Japanese (2033 cases and
      2365 controls) and Chinese populations (412 cases, 464 controls and 601 trios),
      the major groups analyzed in association studies of the CHI3L1 gene. The meta
      analysis in Japanese populations showed stronger evidence for the association of
      schizophrenia with SNP4 (p=0.003), while the meta-analysis in Chinese populations
      showed an association with a different variant (SNP3) (p=0.003). We conclude that
      the genetic variants in the CHI3L1 gene have ethnic heterogeneity and confer a
      susceptibility to schizophrenia in Asian populations.

PMID- 20051318
TI  - Differential processing of metacognitive evaluation and the neural circuitry of
      the self and others in schizophrenia: a pilot study.
AB  - BACKGROUND: Impaired awareness of the self and others (i.e., metacognitive
      evaluations) are seen in schizophrenia. We compared patterns of activation in
      schizophrenia (SZ) and nonclinical subjects during a functional magnetic
      resonance imaging (fMRI) task of metacognitive evaluations that has been
      demonstrated to engage the neural circuitry of the self in healthy subjects.
      METHODS: Eleven SZ subjects (7 males, mean age 26.6+/-8) and 10 healthy control
      subjects (4 males, mean age 29.6+/-8.4) were enrolled. Participants completed two
      runs of a metacognitive evaluation task (self vs. other vs. word meaning). fMRI
      data was obtained using a full body Bruker MedSped 4.0Tesla system. Group
      contrasts were performed using an uncorrected p<0.005 with a 50voxel extent
      threshold. RESULTS: We observed a significant hypoactivation in the left superior
      temporal sulcus (STS) during metacognitive evaluations of others (OE) vs.
      semantic positivity evaluations (SPE) and a trend toward significant
      hypoactivation in the OE vs. self evaluations (SE) in the SZ group. Significant
      hypoactivation was also seen in the right inferior temporal gyrus (ITG) in the OE
      vs. SE contrasts in the SZ group. A trendworthy hypoactivation was seen in the SZ
      group in the right middle frontal gyrus and pole of the left STS during OE vs.
      SPE and SE contrasts respectively. CONCLUSIONS: These results extend previous
      findings of impaired metacognitive evaluative processes in schizophrenia to
      aberrations of the neural circuitry implicated in self/other awareness among SZ
      patients. Greater understanding of the neural basis of deficits of self/other
      awareness in early schizophrenia may contribute to improvements in the
      identification and treatment of individuals at risk for the illness.

PMID- 20051319
TI  - The potential of stem cells in the treatment of knee cartilage defects.
AB  - Cartilage is frequently damaged but only shows a limited capacity for repair.
      There are a number of treatment strategies currently available for the repair of
      articular cartilage defects including abrasion chondroplasty, subchondral
      drilling, microfracture and mosaicplasty but these show variable results. For the
      younger patients, there is great interest in the potential of cell-based
      strategies to provide a biological replacement of damaged cartilage using
      autologous chondrocytes. The results of clinical studies using these cell-based
      techniques do not conclusively show improvement over conventional techniques.
      These techniques also do not consistently result in the formation of the desired
      hyaline cartilage rather than fibrocartilage. Mesenchymal stem cells present a
      promising cell source for cartilage repair. Mesenchymal stem cells have been
      isolated from a number of adult tissues including the bone marrow and the
      synovial fat pad. These cells have the ability to proliferate in culture and
      differentiate down different pathways including the chondrogenic pathway. In the
      first instance, differentiated stem cells can be used for the repair of localised
      cartilage defects by producing hyaline cartilage. In the future, this strategy
      has the potential to be extended to treat more generalised cartilage defects,
      especially as the cell source is not a limiting factor. The use of cell-based
      therapies also allows the versatility of using scaffolds and growth factors, with
      recombinant proteins or gene therapy. A number of challenges however still need
      to be overcome including further work on identifying the optimal source of stem
      cells, along with refining the conditions that enhance expansion and
      chondrogenesis.

PMID- 20051320
TI  - Multi-ligament instability after early dislocation of a primary total knee
      replacement - case report.
AB  - Peripheral nerve blocks have found increased popularity in providing prolonged
      post-operative analgesia following total knee replacement surgery. They generally
      provide effective analgesia with fewer complications than epidurals. This report
      describes an acute low-energy knee dislocation after a well balanced, fixed
      bearing, cruciate-retaining primary total knee replacement performed under a
      spinal anaesthetic with combined complimentary femoral and sciatic nerve blocks.
      The dislocation was not accompanied by neurovascular compromise. Due to the
      subsequent instability and injury to both collaterals, the posterior cruciate
      ligament and posterolateral corner structures, the knee was treated with a
      rotating-hinge revision total knee replacement. The dislocation occurred whilst
      the peripheral nerve blocks (PNB) were still working. We review our incidence of
      PNB related complications and conclude that PNB remain a safe and effective
      analgesia for total knee replacements. However, we advocate that ward staff and
      patients should be sufficiently educated to ensure that unaided post-operative
      mobilisation is prevented until such a time that patients have regained complete
      voluntary muscle control.

PMID- 20051321
TI  - Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of
      disease.
AB  - Arrhythmogenic right ventricular cardiomyopathy is a primary heart muscle
      disorder characterized by the early occurrence of arrhythmias often out of
      proportion to the extent of structural remodeling and contractile derangement.
      Approximately 40% of patients with arrhythmogenic right ventricular
      cardiomyopathy have one or more mutations in genes encoding proteins in
      desmosomes, intercellular adhesion junctions which, in cardiac myocytes, reside
      within intercalated disks. Some desmosomal proteins fulfill roles both as
      structural proteins in cell-cell adhesion junctions and as signaling molecules in
      pathways mediated by Wnt ligands. Evidence is increasing that mutations in
      desmosomal proteins can perturb the normal balance of critical proteins in
      junctions and the cytosol which, in turn, could alter gene expression by
      circumventing normal Wnt signaling pathways. This review highlights recent
      advances in understanding the pathogenesis of arrhythmogenic right ventricular
      cardiomyopathy and presents evidence suggesting that the disease is caused by a
      combination of altered cellular biomechanical behavior and altered signaling.

PMID- 20051322
TI  - Molecular identification of the HLA-DRB1-DQB1 for diagnosis and follow-up of
      acute leukemias.
AB  - We analyzed a group of 45 Brazilian individuals, 30 with acute myeloid leukemia
      (AML), 15 with acute lymphoid leukemia (ALL) and 100 healthy controls to assess
      genetic factor risk and HLA association contribution to the disease. Patient
      rates were compared with age and sex-matched control groups by directly typing
      the HLA-DRB1/3/4/5 and -DQB1 loci by PCR analysis. We observed significantly
      increased allelic distribution of HLA-DRB107 in AML patients and of HLA-DRB103 in
      ALL patients, which suggests that individuals in both groups are susceptible to
      the disease. We also found significantly decreased allelic distribution of HLA
      DQB104 in AML patients and of HLA-DRB104 and -DQB103 in ALL patients, which
      suggests protection against the disease. We further found increased HLA-DRB107
      and -DQB102 haplotypes in AML patients, which suggests susceptibility to the
      disease and decreased HLA-DRB104 and -DQB103 haplotypes in ALL patients, which
      also suggests protection against the disease. Future studies with larger and/or
      multicentric samples will be required for better comprehension of the HLA role in
      acute leukemia pathogenesis.

PMID- 20051323
TI  - Precautions related to midline sternotomy in cardiac surgery: a review of
      mechanical stress factors leading to sternal complications.
AB  - BACKGROUND: After midline sternotomy patients are instructed on activity
      precautions to avoid sternal wound complications. We questioned how restrictive
      these precautions must be, since they can lead to a postoperative decrease in
      quality of life. AIMS: To identify mechanical stress factors causing sternal
      instability and infection in order to create evidence based guidelines for
      activity following sternotomy. METHODS: Literature review. RESULTS: No evidence
      was found to support weight limitation regarding activity, as long as the upper
      arms are kept close to the body and activity is within a pain-free range.
      RECOMMENDATIONS: Avoid stretching both arms backwards at the same time (10 days);
      loaded activities should be done with the elbows close to the body (eight weeks);
      only move arms within a pain-free range; use leg rolling with counterweighing
      when getting in and out of bed; when coughing cross the arms in a "self-hugging"
      posture; supportive bra or vest is recommended when breast cup>or=D, body mass
      index>or=35 or frequent cough. CONCLUSION: This study provides insights into
      mechanical stress factors acting upon sternum and the overlying skin.
      RECOMMENDATIONS on activity precautions based on these finding have a patient
      supportive approach focusing on possibilities and not restrictions.

PMID- 20051324
TI  - Vagal control of mucociliary clearance in murine lungs: a study in a chronic
      preparation.
AB  - We conducted several experiments that focused on the effect of vagal control on
      mucociliary clearance (MCC) in murine lungs. We hypothesized that loss of vagal
      control by chronic denervation (i.e. vagotomy) would reduce both basal MCC and
      the increase in MCC typically observed upon stimulation of capsaicin sensitive C
      fibers. Vagotomy was performed on the right side of C57BL/6 mice and MCC was
      measured 5 days later. Mucociliary clearance was measured by gamma scintigraphy
      after oropharyngeal aspiration of the radioisotope (99m)technetium and was
      expressed as the amount of radioactivity removed from the right lung 6h later.
      Baseline MCC was unaffected by vagotomy, averaging 6.5+/-4.9% and 6.8+/-5.8%, in
      6 vagotomized and 6 non-vagotomized mice (controls), respectively. Mucociliary
      clearance increased significantly to 12.7+/-5.9% in 9 non-vagotomized mice
      treated with 1.6 x 10(-9) M capsaicin, a vagally-mediated, nociceptor stimulus
      (p=0.041). Capsaicin was admixed with (99m)technetium and administered by
      oropharyngeal aspiration. In contrast, MCC was unchanged from control values in 9
      vagotomized, capsaicin-treated animals, averaging 6.0+/-5.5% (p=0.024). These
      findings suggest that loss of vagal control through denervation does not affect
      basal MCC in C57BL/6 mice, but does appear to reduce the capacity of mice to
      respond to nociceptor agents that stimulate MCC. These data could have
      implications for patients whose lungs are denervated due to lung transplantation,
      since they may be at risk for an inadequate MCC response to inhaled irritants and
      inflammatory mediators, which are also nociceptor stimuli.

PMID- 20051325
TI  - A L-cysteine sensor based on Pt nanoparticles/poly(o-aminophenol) film on glassy
      carbon electrode.
AB  - Platinum nanoparticles (nano-Pt) and poly(o-aminophenol) (POAP) were fabricated
      onto the glassy carbon electrode(GCE) to form the nano-Pt/POAP/GCE for the
      electrochemical determination of L-cysteine. The POAP film was obtained through
      electrochemical polymerization of o-aminophenol on GCE. The nano-Pt was
      electrochemically deposited onto the surface of the activated POAP/GCE The
      resultant nano-Pt/POAP/GCE was characterized by scanning electron microscopy
      (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV),
      and showed excellent electrochemical response to L-cysteine at low oxidative
      potential in Britton-Robinson (BR) buffer solution (pH=3.0), with good stability
      and sensitivity, and featured with a low detection limit (0.08 microM,
      signal/noise=3) and wide linear range (0.4 microM-6.3mM).The mechanism for the
      electrochemical oxidation of L-cysteine on the nano-Pt/POAP/GCE was also
      investigated.

PMID- 20051326
TI  - Enzymatic flow injection method for rapid determination of choline in urine with
      electrochemiluminescence detection.
AB  - In order to determine trace choline in human urine, a flow injection analysis
      (FIA) system has been developed by coupling an enzyme reactor with an
      electrochemiluminescence (ECL) detector. The enzyme reactor is prepared by
      covalently immobilizing choline oxidase (ChOx) onto the aminopropyl-controlled
      pore glass beads, which are then carefully packed into a micro column. The enzyme
      reactor catalyzes the production of hydrogen peroxide that is in direct
      proportion to the concentration of choline. In this study, the enzymatically
      produced hydrogen peroxide was detected by an ECL detector positioned at the down
      stream of an enzyme reactor based on the luminol/H(2)O(2) ECL system. Under the
      optimized condition, the enzymatic FIA/ECL provided high sensitivity for the
      determination of choline with the detection limit as low as 0.05 microM (absolute
      detection limit was at sub pmol level). The method was successfully applied in
      the determination of choline in the samples of human urine, and the analytical
      results were in good agreement with those obtained by using the microbore HPLC
      with an immobilized enzyme reactor-electrochemical detection system.

PMID- 20051327
TI  - Electrochemical oxidation of amphetamine-like drugs and application to
      electroanalysis of ecstasy in human serum.
AB  - Amphetamine and amphetamine-like drugs are popular recreational drugs of abuse
      because they are powerful stimulants of the central nervous system. Due to a
      dramatic increase in the abuse of methylenedioxylated derivatives, individually
      and/or in a mixture, and to the incoherent and contradictory interpretation of
      the electrochemical data available on this subject, a comprehensive study of the
      redox properties of amphetamine-like drugs was accomplished. The oxidative
      behaviour of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine
      (MDA) and methylenedioxymethamphetamine (MDMA) was studied in different buffer
      systems by cyclic, differential pulse and square-wave voltammetry using a glassy
      carbon electrode. A quantitative electroanalytical method was developed and
      successfully applied to the determination of MDMA in seized samples and in human
      serum. Validation parameters, such as sensitivity, precision and accuracy, were
      evaluated. The results found using the developed electroanalytical methodology
      enabled to gather some information about the content and amount of MDMA present
      in ecstasy tablets found in Portugal. Moreover, the data found in this study
      outlook the possibility of using the voltammetric methods to investigate the
      potential harmful effects of interaction between drugs such as MDMA and
      methamphetamine and other substances often used together in ecstasy tablets.

PMID- 20051328
TI  - Dependence of catalytic activity and long-term stability of enzyme hydrogel films
      on curing time.
AB  - Enzyme hydrogels were prepared on carbon film electrodes using glucose oxidase
      and an epoxide crosslinking agent. The catalytic activity of the gels was found
      to depend strongly on curing time. The competing effects of increased mechanical
      stability and decreased enzyme activity as curing time increases resulted in the
      highest catalytic activity for films cured for 24h at 25 degrees C. Weekly
      electrochemical measurements established that the long-term stabilities of all
      hydrogels cured for 24-72 h were similar, with close to half of the initial
      catalytic activity being retained after immersion for 3 months in agitated
      phosphate buffer solution at 25 degrees C.

PMID- 20051329
TI  - Patient segregation and aggressive antibiotic eradication therapy can control
      methicillin-resistant Staphylococcus aureus at large cystic fibrosis centres.
AB  - BACKGROUND: The prevalence of MRSA in patients with CF has risen in recent years.
      We adhere to a policy of segregation and barrier nursing to manage patients with
      MRSA, and we actively pursue eradication of MRSA. We have evaluated our
      experiences of MRSA infection in our large adult CF centre. METHOD: A
      retrospective review of all MRSA-positive patients from 1998 to 2008 was
      undertaken. Isolates were subjected to molecular identification to elucidate
      possible patient-to-patient transmission events. Eradication attempts were
      scrutinised. RESULTS: We have maintained a low incidence and prevalence (below
      3%) of MRSA within this large cohort. A total of 15 pulsotypes of MRSA were
      identified among the 24 isolates examined, epidemiological data suggested no
      patient-patient transmission. Based on 6 month follow-up data, successful
      eradication was achieved in 81% patients. This includes those who had harboured
      infection for some time. Twenty-one (80.8%) required only one course of
      treatment, 3 (11.6%) patients required two different regimes and 2 (7.5%)
      required three courses to fully eradicate the organism. CONCLUSION: Strict
      infection control procedures can control MRSA infection and keep the prevalence
      low in CF clinics. Eradication is achievable in the majority of patients even
      when significant time has lapsed from initial isolation. In some instances, up to
      3 courses of antibiotics were required to achieve eradication.

PMID- 20051330
TI  - In vivo impedance imaging with total variation regularization.
AB  - We show that electrical impedance tomography (EIT) image reconstruction
      algorithms with regularization based on the total variation (TV) functional are
      suitable for in vivo imaging of physiological data. This reconstruction approach
      helps to preserve discontinuities in reconstructed profiles, such as step changes
      in electrical properties at interorgan boundaries, which are typically smoothed
      by traditional reconstruction algorithms. The use of the TV functional for
      regularization leads to the minimization of a nondifferentiable objective
      function in the inverse formulation. This cannot be efficiently solved with
      traditional optimization techniques such as the Newton method. We explore two
      implementations methods for regularization with the TV functional: the lagged
      diffusivity method and the primal dual-interior point method (PD-IPM). First we
      clarify the implementation details of these algorithms for EIT reconstruction.
      Next, we analyze the performance of these algorithms on noisy simulated data.
      Finally, we show reconstructed EIT images of in vivo data for ventilation and
      gastric emptying studies. In comparison to traditional quadratic regularization,
      TV regularization shows improved ability to reconstruct sharp contrasts.

PMID- 20051332
TI  - A combined sEMG and accelerometer system for monitoring functional activity in
      stroke.
AB  - Remote monitoring of physical activity using body-worn sensors provides an
      alternative to assessment of functional independence by subjective, paper-based
      questionnaires. This study investigated the classification accuracy of a combined
      surface electromyographic (sEMG) and accelerometer (ACC) sensor system for
      monitoring activities of daily living in patients with stroke. sEMG and ACC data
      (eight channels each) were recorded from 10 hemiparetic patients while they
      carried out a sequence of 11 activities of daily living (identification tasks),
      and 10 activities used to evaluate misclassification errors (nonidentification
      tasks). The sEMG and ACC sensor data were analyzed using a multilayered neural
      network and an adaptive neuro-fuzzy inference system to identify the minimal
      sensor configuration needed to accurately classify the identification tasks, with
      a minimal number of misclassifications from the nonidentification tasks. The
      results demonstrated that the highest sensitivity and specificity for the
      identification tasks was achieved using a subset of four ACC sensors and adjacent
      sEMG sensors located on both upper arms, one forearm, and one thigh,
      respectively. This configuration resulted in a mean sensitivity of 95.0%, and a
      mean specificity of 99.7% for the identification tasks, and a mean
      misclassification error of < 10% for the nonidentification tasks. The findings
      support the feasibility of a hybrid sEMG and ACC wearable sensor system for
      automatic recognition of motor tasks used to assess functional independence in
      patients with stroke.

PMID- 20051336
TI  - Graph formations of partial-order multiple-sequence alignments using nanoscale,
      microscale, and multiscale reconfigurable meshes.
AB  - In this paper, we show how to form partial-order multiple-sequence alignment
      graphs on two types of reconfigurable mesh architectures. The first
      reconfigurable mesh is a standard microscale that uses electrical interconnects,
      while the second type of reconfigurable mesh can be implemented at a nanoscale
      level and employs spin waves for interconnectivity. We consider graph formations
      for two cases. In one case, the number of distinct variables in the data
      sequences is constant. In the other case, it can be as much as O(N). We show that
      given O(N) aligned sequences of length L, we can combine the sequences to form a
      graph in O(1) time, using either architecture if there is a constant number of
      distinct variables in the sequence. Otherwise, it will take O(1) time if we use
      the spin-wave model and O(N) time if we use the standard very large scale
      integration version.

PMID- 20051337
TI  - Removal of hybridization and scanning noise from microarrays.
AB  - Microarray technology for measuring gene expression values has created
      significant opportunities for advances in disease diagnosis and individualized
      treatment planning. However, the random noise introduced by the sample
      preparation, hybridization, and scanning stages of microarray processing creates
      significant inaccuracies in the gene expression levels, and hence presents a
      major barrier in realizing the anticipated advances. Literature presents several
      methodologies for noise reduction, which can be broadly categorized as: 1) model
      based approaches for estimation and removal of hybridization noise; 2) approaches
      using commonly available image denoising tools; and 3) approaches involving the
      need for control sample(s). In this paper, we present a novel methodology for
      identifying and removing hybridization and scanning noise from microarray images,
      using a dual-tree-complex-wavelet-transform-based multiresolution analysis
      coupled with bivariate shrinkage thresholding. The key features of our
      methodology include consideration of inherent features and type of noise specific
      to microarray images, and the ability to work with a single microarray without
      needing a control. Our methodology is first benchmarked on a fabricated dataset
      that mimics a real microarray probe dataset. Thereafter, our methodology is
      tested on datasets obtained from a number of Affymetrix GeneChip human genome HG
      U133 Plus 2.0 arrays, processed on HCT-116 cell line at the Microarray Core
      Facility of Moffitt Cancer Center and Research Institute. The results indicate an
      appreciable improvement in the quality of the microarray data.

PMID- 20051338
TI  - Rotational maneuver of ferromagnetic nanowires for cell manipulation.
AB  - 1-D magnetic nanowires provide a powerful tool for investigating biological
      systems because such nanomaterials possess unique magnetic properties, which
      allow effective manipulation of cellular and subcellular objects. In this study,
      we report the rotational maneuver of ferromagnetic nanowires and their
      applications in cell manipulation. The rotational maneuver is studied under two
      different suspension conditions. The rotation of nanowires in the fluid is
      analyzed using Stokes flow assumption. Experimental results show that when the
      nanowires develop contacts with the bottom surfaces, the rotational maneuver
      under a modest external magnetic field can generate rapid lateral motion. The
      floating nanowires, on the other hand, do not exhibit substantial lateral
      displacements. Cell manipulation using skeletal myoblasts C2C12 shows that living
      cells can be manipulated efficiently on the bottom surface by the rotational
      maneuver of the attached nanowires. We also demonstrate the use of rotational
      maneuver of nanowires for creating 3-D nanowire clusters and multicellular
      clusters. This study is expected to add to the knowledge of nanowire-based cell
      manipulation and contribute to a full spectrum of control strategies for
      efficient use of nanowires for micro-total-analysis. It may also facilitate
      mechanobiological studies at cellular level, and provide useful insights for
      development of 3-D in vivo-like multicellular models for various applications in
      tissue engineering.

PMID- 20051339
TI  - Fast transient thermal analysis of gold nanoparticles in tissue-like medium.
AB  - Gold-nanoparticle-based hyperthermia has attracted considerable attention in the
      recent ten years in cancer treatment. In hyperthermia-based cancer treatment, in
      order to produce efficient thermal therapy yet without excessive heat damage to
      human body, besides the steady-state thermal condition, the transient thermal
      response is of vital importance. As part of theoretical research associated with
      nanoparticle-mediated hyperthermia therapy for cancer treatment, the transient
      heat transfer process of laser interacting with gold nanoparticle in tissue-like
      medium is investigated. Within the framework of dual-phase-lag (DPL) model, this
      paper focuses on the microscopic heat transfer performance of a gold nanoparticle
      in a surrounding medium. A semianalytical solution of 1-D nonhomogenous DPL
      equation in spherical coordinates is presented for a heat transfer process with a
      constant laser heat source and a short-pulsed laser heating source. Results show
      that the transient temperature calculated by DPL model greatly exceeds that
      predicted by the classical diffusion model, with either a constant source or a
      pulsed source. This phenomenon is mainly attributed by the phase lag of heat flux
      in the surrounding tissue.

PMID- 20051340
TI  - Design and characterization of a three-terminal transcriptional device through
      polymerase per second.
AB  - In this paper, we provide an in silico input-output characterization of a three
      terminal transcriptional device employing polymerase per second (PoPS) as input
      and output. The device is assembled from well-characterized parts of the
      bacteriophage lambda switch transcriptional circuit. We draw the analogy between
      voltage and protein concentration and between current and PoPS to demonstrate
      that the characteristics of the three-terminal transcriptional device are
      qualitatively similar to those of a bipolar junction transistor (BJT). In
      particular, as it occurs in a BJT, the device can be tuned to operate either as a
      linear amplifier or as a switch. When the device operates as a linear amplifier,
      gains of twofolds can be obtained, which are considerably smaller than those
      obtained in a BJT (in which 100-fold amplification gains can be reached). This
      fact suggests that the parts extracted from natural transcriptional systems may
      be naturally designed mostly to process and store information as opposed to
      amplify signals.

PMID- 20051341
TI  - An examplar-based approach for texture compaction synthesis and retrieval.
AB  - A texture representation should corroborate various functions of a texture. In
      this paper, we present a novel approach that incorporates texture features for
      retrieval in an examplar-based texture compaction and synthesis algorithm. The
      original texture is compacted and compressed in the encoder to obtain a thumbnail
      texture, which the decoder then synthesizes to obtain a perceptually high quality
      texture. We propose using a probabilistic framework based on the generalized EM
      algorithm to analyze the solutions of the approach. Our experiment results show
      that a high quality synthesized texture can be generated in the decoder from a
      compressed thumbnail texture. The number of bits in the compressed thumbnail is
      400 times lower than that in the original texture and 50 times lower than that
      needed to compress the original texture using JPEG2000. We also show that, in
      terms of retrieval and synthesization, our compressed and compacted textures
      perform better than compressed cropped textures and compressed compacted textures
      derived by the patchwork algorithm.

PMID- 20051342
TI  - Trajectory classification using switched dynamical hidden Markov models.
AB  - This paper proposes an approach for recognizing human activities (more
      specifically, pedestrian trajectories) in video sequences, in a surveillance
      context. A system for automatic processing of video information for surveillance
      purposes should be capable of detecting, recognizing, and collecting statistics
      of human activity, reducing human intervention as much as possible. In the method
      described in this paper, human trajectories are modeled as a concatenation of
      segments produced by a set of low level dynamical models. These low level models
      are estimated in an unsupervised fashion, based on a finite mixture formulation,
      using the expectation-maximization (EM) algorithm; the number of models is
      automatically obtained using a minimum message length (MML) criterion. This leads
      to a parsimonious set of models tuned to the complexity of the scene. We describe
      the switching among the low-level dynamic models by a hidden Markov chain; thus,
      the complete model is termed a switched dynamical hidden Markov model (SD-HMM).
      The performance of the proposed method is illustrated with real data from two
      different scenarios: a shopping center and a university campus. A set of human
      activities in both scenarios is successfully recognized by the proposed system.
      These experiments show the ability of our approach to properly describe
      trajectories with sudden changes.

PMID- 20051343
TI  - Multistatic synthetic aperture radar image formation.
AB  - In this paper, we consider a multistatic synthetic aperture radar (SAR) imaging
      scenario where a swarm of airborne antennas, some of which are transmitting,
      receiving or both, are traversing arbitrary flight trajectories and transmitting
      arbitrary waveforms without any form of multiplexing. The received signal at each
      receiving antenna may be interfered by the scattered signal due to multiple
      transmitters and additive thermal noise at the receiver. In this scenario,
      standard bistatic SAR image reconstruction algorithms result in artifacts in
      reconstructed images due to these interferences. In this paper, we use microlocal
      analysis in a statistical setting to develop a filtered-backprojection (FBP) type
      analytic image formation method that suppresses artifacts due to interference
      while preserving the location and orientation of edges of the scene in the
      reconstructed image. Our FBP-type algorithm exploits the second-order statistics
      of the target and noise to suppress the artifacts due to interference in a mean
      square sense. We present numerical simulations to demonstrate the performance of
      our multistatic SAR image formation algorithm with the FBP-type bistatic SAR
      image reconstruction algorithm. While we mainly focus on radar applications, our
      image formation method is also applicable to other problems arising in fields
      such as acoustic, geophysical and medical imaging.

PMID- 20051344
TI  - Development and optimization of regularized tomographic reconstruction algorithms
      utilizing equally-sloped tomography.
AB  - We develop two new algorithms for tomographic reconstruction which incorporate
      the technique of equally-sloped tomography (EST) and allow for the optimized and
      flexible implementation of regularization schemes, such as total variation
      constraints, and the incorporation of arbitrary physical constraints. The
      founding structure of the developed algorithms is EST, a technique of tomographic
      acquisition and reconstruction first proposed by Miao in 2005 for performing
      tomographic image reconstructions from a limited number of noisy projections in
      an accurate manner by avoiding direct interpolations. EST has recently been
      successfully applied to coherent diffraction microscopy, electron microscopy, and
      computed tomography for image enhancement and radiation dose reduction. However,
      the bottleneck of EST lies in its slow speed due to its higher computation
      requirements. In this paper, we formulate the EST approach as a constrained
      problem and subsequently transform it into a series of linear problems, which can
      be accurately solved by the operator splitting method. Based on these
      mathematical formulations, we develop two iterative algorithms for tomographic
      image reconstructions through EST, which incorporate Bregman and continuative
      regularization. Our numerical experiment results indicate that the new
      tomographic image reconstruction algorithms not only significantly reduce the
      computational time, but also improve the image quality. We anticipate that EST
      coupled with the novel iterative algorithms will find broad applications in X-ray
      tomography, electron microscopy, coherent diffraction microscopy, and other
      tomography fields.

PMID- 20051345
TI  - High-resolution imaging using a wideband MIMO radar system with two distributed
      arrays.
AB  - Imaging a fast maneuvering target has been an active research area in past
      decades. Usually, an array antenna with multiple elements is implemented to avoid
      the motion compensations involved in the inverse synthetic aperture radar (ISAR)
      imaging. Nevertheless, there is a price dilemma due to the high level of hardware
      complexity compared to complex algorithm implemented in the ISAR imaging system
      with only one antenna. In this paper, a wideband multiple-input multiple-output
      (MIMO) radar system with two distributed arrays is proposed to reduce the
      hardware complexity of the system. Furthermore, the system model, the equivalent
      array production method and the imaging procedure are presented. As compared with
      the classical real aperture radar (RAR) imaging system, there is a very important
      contribution in our method that the lower hardware complexity can be involved in
      the imaging system since many additive virtual array elements can be obtained.
      Numerical simulations are provided for testing our system and imaging method.

PMID- 20051346
TI  - Segmentation and classification of hyperspectral images using minimum spanning
      forest grown from automatically selected markers.
AB  - A new method for segmentation and classification of hyperspectral images is
      proposed. The method is based on the construction of a minimum spanning forest
      (MSF) from region markers. Markers are defined automatically from classification
      results. For this purpose, pixelwise classification is performed, and the most
      reliable classified pixels are chosen as markers. Each classification-derived
      marker is associated with a class label. Each tree in the MSF grown from a marker
      forms a region in the segmentation map. By assigning a class of each marker to
      all the pixels within the region grown from this marker, a spectral-spatial
      classification map is obtained. Furthermore, the classification map is refined
      using the results of a pixelwise classification and a majority voting within the
      spatially connected regions. Experimental results are presented for three
      hyperspectral airborne images. The use of different dissimilarity measures for
      the construction of the MSF is investigated. The proposed scheme improves
      classification accuracies, when compared to previously proposed classification
      techniques, and provides accurate segmentation and classification maps.

PMID- 20051347
TI  - [Publication of biological samples collections catalogues by tumor banks].
AB  - Biobanks in general, and specifically tumour banks, are considered as essential
      tools for the development of translational and clinical research in biology and
      oncology. Biobank tasks include the collection and preservation of biological
      samples, and their association with information that will be essential for
      further scientific use ("annotations" that allow for the "qualification" of
      biological samples in biological resource). A collection is made of a series of
      biological resource that are representative of a homogeneous group of individuals
      or patients that are defined on the basis of clinical or biological information.
      Collections are used by scientists that are aware of their existence. In the
      absence of a published catalogue, this awareness is most often limited to
      research teams that are geographically close, or to investigators who already
      established collaborative projects with medical teams within the hospital that
      operates the tumour bank. Publications of catalogues, especially digitalized and
      online catalogues, should foster the development of high-level, large-scale and
      multicentric scientific projects. In addition, tumour banks will formalize rules
      that allow publication of collections, and upstream, rules that are used to
      qualify biological samples in biological resource: this should translate in an
      improved overall quality of samples and annotations. Tumour bank catalogues
      remain relatively few; however, some recent achievements established the "proof
      of concept" and already raise questions regarding rules for publication. It will
      be important to demonstrate that these high expectations translate into
      measurable benefits.

PMID- 20051348
TI  - [Chemotherapy induced emesis: pathophysiology and prevention].
AB  - Nausea and emesis are one of the most feared secondary effect of chemotherapy.
      The development of antiemetic therapies has increased after the introduction of
      cisplatin, a cytotoxin with the highest emetic potential. Chemotherapy-induced
      nausea and vomiting (CINV) have been classified into acute, delayed and
      anticipatory based on the time of onset. According to the percentage of nausea
      and emesis without any antiemetic treatment, chemotherapy is divised into highly,
      moderate, low and very low emetic potential. The discovery of emetics stimuli
      neurotransmitters and their receptors has led to the introduction of new
      molecules which associated with steroids have prevented nausea and vomiting
      chemotherapy-induced for 70 to 80% of the patients receiving chemotherapy with
      high emetic potential. Numerous studies have evaluated the various antiemetics
      and recommendations were issued by learned societies in US and Europe. This text
      discusses the physiopathology of nausea and vomiting, the development of anti
      emetics and the new discovered antiemetics. Finally, a synthesis of the
      recommandations from the guidelines developed by the Multinational Association of
      Supportive Care in Cancer (MASCC), the American Society of Clinical Oncology
      (ASCO), the National Comprehensive Cancer Network (NCCN) and the European Society
      for Medical Oncology (ESMO) is presented.

PMID- 20051349
TI  - [Neoadjuvant chemotherapy in non-small cell lung cancer: current state and
      future].
AB  - Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer
      related mortality in the world. The combination of chemotherapy and surgery is a
      standard of care for resectable NSCLC. If the adjuvant chemotherapy is a
      standard, the role of neoadjuvant chemotherapy is still debated. Most trials of
      neoadjuvant chemotherapy were closed when the positive studies of adjuvant
      chemotherapy were published. Only the Spanish trial NATCH, designed to compare
      the neoadjuvant chemotherapy in the adjuvant chemotherapy, was fully completed.
      Therefore, the trials of preoperative chemotherapy lack strength to become proof
      of concept. Confirmation will come from meta-analyses. Two of them are positive.
      Others are in progress. The current research is to select the patients according
      to predictive factors to chemotherapy response.

PMID- 20051350
TI  - Timing and the control of rhythmic upper-limb movements.
AB  - Accurate timing of limb displacement is crucial for effective motor control. The
      authors examined the effects of movement velocity, duration, direction, added
      mass, and auditory cueing on timing, spatial, and trajectory variability of
      single- and multijoint rhythmic movements. During single-joint movements,
      increased velocity decreased timing and spatial variability, whereas increased
      movement duration increased timing variability but decreased spatial variability.
      For multijoint movements, regardless of condition, increasing velocity decreased
      joint timing, spatial, and trajectory variability, but all hand variabilities
      were unaffected by velocity, duration, load, or direction. Timing, spatial, and
      trajectory variability was greater at the shoulder compared with the elbow and
      minimal at the hand, supporting the notion that reaching movements are planned in
      hand space as opposed to joint space.

PMID- 20051351
TI  - Deterministic and stochastic postural processes: effects of task, environment,
      and age.
AB  - Upright standing is always environmentally embedded and typically co-occurs with
      another (suprapostural) activity. In the present study, the authors investigate
      how these facts affect postural dynamics in an experiment in which younger (M age
      = 20.23 years, SD = 2.02 years) and older (M age = 75.26 years, SD = 4.87 years)
      participants performed a task of detecting letters in text or maintaining gaze
      within a target while standing upright in a structured or nonstructured
      stationary environment. They extracted the coefficients of drift (indexing
      attractor strength) and diffusion (indexing noise strength) from the center of
      pressure (COP) time series in anteroposterior (AP) and mediolateral (ML) axes.
      COP standard deviation decreased with drift and increased with diffusion. The
      authors found that structure reduced AP diffusion for both groups and that letter
      detection reduced younger SDAP (primarily by diffusion decrease) and increased
      older SDML (primarily by drift decrease). For older and younger participants, ML
      drift was lower during letter detection. Further, in older letter detection,
      larger visual contrast sensitivity was associated with larger ML drift and
      smaller SDML, raising the hypotheses that ML sway helps information detection and
      reflects neurophysiological age.

PMID- 20051352
TI  - Modelling the crop: from system dynamics to systems biology.
AB  - There is strong interplant competition in a crop stand for various limiting
      resources, resulting in complex compensation and regulation mechanisms along the
      developmental cascade of the whole crop. Despite decades-long use of principles
      in system dynamics (e.g. feedback control), current crop models often contain
      many empirical elements, and model parameters may have little biological meaning.
      Building on the experience in designing the relatively new model GECROS, we
      believe models can be made less empirical by employing existing physiological
      understanding and mathematical tools. In view of the potential added value of
      robust crop modelling to classical quantitative genetics, model input parameters
      are increasingly considered to represent 'genetic coefficients'. The advent of
      functional genomics and systems biology enables the elucidation of the molecular
      genetic basis of these coefficients. A number of case studies, in which the
      effects of quantitative trait loci or genes have been incorporated into existing
      ecophysiological models, have shown the promise of using models in analysing
      genotype-phenotype relationships of some crop traits. For further progress, crop
      models must be upgraded based on understanding at lower organizational levels for
      complicated phenomena such as sink formation in response to environmental cues,
      sink feedback on source activity, and photosynthetic acclimation to the
      prevailing environment. Within this context, the recently proposed 'crop systems
      biology', which combines modern genomics, traditional physiology and
      biochemistry, and advanced modelling, is believed ultimately to realize the
      expected roles of in silico modelling in narrowing genotype-phenotype gaps. This
      review summarizes recent findings and our opinions on perspectives for modelling
      genotype x environment interactions at crop level.

PMID- 20051353
TI  - The X-factor: visualizing undisturbed root architecture in soils using X-ray
      computed tomography.

PMID- 20051354
TI  - Distinct neural pathways mediate alpha7 nicotinic acetylcholine receptor
      dependent activation of the forebrain.
AB  - alpha(7) nicotinic acetylcholine receptor (nAChR) agonists are candidates for the
      treatment of cognitive deficits in schizophrenia. Selective alpha(7) nAChR
      agonists, such as SSR180711, activate neurons in the medial prefrontal cortex
      (mPFC) and nucleus accumbens shell (ACCshell) in rats, regions important for
      cognitive function. However, the neural substrates involved in these effects
      remain elusive. Here we identify cortically projecting cholinergic neurons in the
      horizontal limb of the diagonal band of Broca (HDB) in the basal forebrain (BF)
      as important targets for alpha(7) nAChR activation, as measured by c-Fos
      immunoreactivity, a marker of neuronal activation. Selective depletion of these
      cholinergic neurons abolishes the SSR180711-induced activation of the mPFC but
      not the ACCshell, demonstrating their critical importance for alpha(7) nAChR
      dependent activation of the mPFC. Contrarily, selective depletion of dopaminergic
      neurons in the ventral tegmental area abolishes the SSR180711-induced activation
      of the ACCshell but not the mPFC or HDB. These results demonstrate 2 distinct
      neural pathways activated by SSR180711. The BF and mPFC are important for
      attentional function and may subserve the procognitive effects of alpha(7) nAChR
      agonists, whereas activation of the ACCshell is implicated in the beneficial
      effect of antipsychotics on the positive symptoms of schizophrenia.

PMID- 20051355
TI  - Functional deficit and recovery of developing sensorimotor networks following
      neonatal hypoxic-ischemic injury in the rat.
AB  - Neonatal hypoxia-ischemia (HI) is the most important cause of brain injury in the
      newborn. Here we studied structural alterations and functional perturbations of
      developing large-scale sensorimotor cortical networks in a rat model of moderate
      HI at postnatal day 3 (P3). At the morphological level, HI led to a disorganized
      barrel pattern in the somatosensory cortex without detectable histological
      changes in the motor cortex. Functional effects were addressed by means of
      epicranial mapping of somatosensory-evoked potentials (SEPs) during the
      postischemic recovery period. At P10, SEPs were immature and evoked activity was
      almost restricted to the somatosensory and motor cortices of the contralateral
      hemisphere. Peak and topographic analyses of epicranial potentials revealed that
      responses were profoundly depressed in both sensory and motor areas of HI
      lesioned animals. At the end of the postnatal period at P21, responses involved
      networks in both hemispheres. SEP amplitude was still depressed in the injured
      sensory region, but it completely recovered in the motor area. These results
      suggest a process of large-scale network plasticity in sensorimotor circuits
      after perinatal ischemic injury. The model provides new perspectives for
      investigating the temporal and spatial characteristics of the recovery process
      following HI and eventually developing therapeutic interventions.

PMID- 20051357
TI  - Neural control of cross-language asymmetry in the bilingual brain.
AB  - Most bilinguals understand their second language more slowly than their first.
      This behavioral asymmetry may arise from the perceptual, phonological,
      lexicosemantic, or strategic components of bilingual word processing. However,
      little is known about the neural source of such language dominance and how it is
      regulated in the bilingual brain. Using functional magnetic resonance imaging, we
      found that unconscious neural priming in bilingual word recognition is language
      nonselective in the left midfusiform gyrus but exhibits a preference for the
      dominant language in the left posterior middle temporal gyrus (MTG). These early
      stage components of reading were located slightly upstream of the left midlateral
      MTG, which exhibited enhanced response during a conscious switch of language.
      Effective connectivity analysis revealed that this language switch is triggered
      by reentrant signals from inferior frontal cortex and not by bottom-up signals
      from occipitotemporal cortex. We further confirmed that magnetic stimulation of
      the same inferior frontal region interferes with conscious language control but
      does not disrupt unconscious priming by masked words. Collectively, our results
      demonstrate that the neural bottleneck in the bilingual brain is a cross-language
      asymmetry of form-meaning association in inferolateral temporal cortex, which is
      overcome by a top-down cognitive control for implementing a task schema in each
      language.

PMID- 20051356
TI  - Brain atrophy in healthy aging is related to CSF levels of Abeta1-42.
AB  - Reduced levels of beta-amyloid(1-42) (Abeta1-42) and increased levels of tau
      proteins in the cerebrospinal fluid (CSF) are found in Alzheimer's disease (AD),
      likely reflecting Abeta deposition in plaques and neuronal and axonal damage. It
      is not known whether these biomarkers are associated with brain atrophy also in
      healthy aging. We tested the relationship between CSF levels of Abeta1-42 and tau
      (total tau and tau phosphorylated at threonine 181) proteins and 1-year brain
      atrophy in 71 cognitively normal elderly individuals. Results showed that under a
      certain threshold value, levels of Abeta1-42 correlated highly with 1-year change
      in a wide range of brain areas. The strongest relationships were not found in the
      regions most vulnerable early in AD. Above the threshold level, Abeta1-42 was not
      related to brain changes, but significant volume reductions as well as
      ventricular expansion were still seen. It is concluded that Abeta1-42 correlates
      with brain atrophy and ventricular expansion in a subgroup of cognitively normal
      elderly individuals but that reductions independent of CSF levels of Abeta1-42 is
      common. Further research and follow-up examinations over several years are needed
      to test whether degenerative pathology will eventually develop in the group of
      cognitively normal elderly individuals with low levels of Abeta1-42.

PMID- 20051358
TI  - Retinotopic coding of extraretinal pursuit signals in early visual cortex.
AB  - During smooth pursuit, the image of the target is stabilized on the fovea,
      implying that speed judgments made during pursuit must rely on an extraretinal
      signal providing precise eye speed information. To characterize the introduction
      of such extraretinal signal into the human visual system, we performed a
      factorial, functional magnetic resonance imaging experiment, in which we
      manipulated the factor eye movement, with "fixation" and "pursuit" as levels, and
      the factor task, with "speed" and "form" judgments as levels. We hypothesized
      that the extraretinal speed signal is reflected as an interaction between speed
      judgments and pursuit. Random effects analysis yielded an interaction only in
      dorsal early visual cortex. Retinotopic mapping localized this interaction on the
      horizontal meridian (HM) between dorsal areas visual 2 and 3 (V2/V3) at 1-2
      degrees azimuth. This corresponded to the position the pursuit target would have
      reached, if moving retinotopically, at the time of the subject's speed judgment.
      Because the 2 V2/V3 HMs are redundant, both may be involved in speed judgments,
      the ventral one involving judgments based on retinal motion and the dorsal one
      judgments requiring an internal signal. These results indicate that an
      extraretinal speed signal is injected into early visual cortex during pursuit.

PMID- 20051359
TI  - Simulating the future of actions in the human corticospinal system.
AB  - Perception of the final position of a moving object or creature is distorted
      forward along its actual or implied motion path, thus enabling anticipation of
      its forthcoming position. In a previous research, we demonstrated that viewing
      static snapshots that imply body actions activates the human motor system. What
      remains unknown, however, is whether extrapolation of dynamic information and
      motor activation are higher for upcoming than past action phases. By using single
      pulse transcranial magnetic stimulation, we found that observation of start and
      middle phases of grasp and flick actions engendered a significantly higher motor
      facilitation than observing their final postures. Differential motor facilitation
      during start and end postures was independent of finger configuration at the
      different hand apertures. Subjective ratings showed that modulation of motor
      facilitation was not due to the amount of implied motion per se but to the
      forward direction of the motion path toward upcoming phases. Thus, motor
      facilitation proved maximal for the snapshots evoking ongoing but incomplete
      actions. The results provide compelling evidence that the frontal component of
      the observation-execution matching system is preferentially activated by the
      anticipatory simulation of future action phases and thus plays an important role
      in the predictive coding of others' motor behaviors.

PMID- 20051360
TI  - State-dependent TMS reveals a hierarchical representation of observed acts in the
      temporal, parietal, and premotor cortices.
AB  - A transcranial magnetic stimulation (TMS) adaptation paradigm was used to
      investigate the neural representation of observed motor behavior in the inferior
      parietal lobule (IPL), ventral premotor cortex (PMv), and in the cortex around
      the superior temporal sulcus (STS). Participants were shown adapting movies of a
      hand or a foot acting on different objects and were asked to compare to the
      movie, a motor act shown in test pictures. The invariant features between
      adapting and test stimuli fitted a 2 x 2 design: same or different action made by
      the same or different effector. Neuronavigated TMS pulses were delivered at the
      onset of each test picture. TMS over the left and right PMv and over the left IPL
      induced a selective shortening of reaction times (RTs) to stimuli showing a
      repeated (adapted) action, regardless of the effector performing it. In a second
      experiment, TMS applied over the left STS induced shortening of RTs for adapted
      actions but only if also the effector was repeated. The results indicate that
      observed motor behavior is encoded with the body part that performs it in the
      temporal lobe. A hierarchically higher level of representation is carried by
      neural populations in the parietofrontal regions, where acts are encoded in an
      abstract way.

PMID- 20051361
TI  - Double dissociation of format-dependent and number-specific neurons in human
      parietal cortex.
AB  - Based on neuroimaging methods, it is a commonly held view that numerical
      representation in the human parietal lobes is format independent. We used a
      transcranial magnetic stimulation adaptation paradigm to examine the existence of
      functionally segregated overlapping populations of neurons for different
      numerical formats and to reveal how numerical information is encoded and
      represented. Based on 2 experiments, we found that right parietal lobe
      stimulation showed a dissociation between digits and verbal numbers, whereas the
      left parietal lobe showed a double dissociation between the different numerical
      formats. Further analysis and modeling also excluded pre- or postrepresentational
      components as the source of the current effects. These results demonstrate that
      both parietal lobes are equipped with format-dependent neurons that encode
      quantity.

PMID- 20051362
TI  - Dopamine influences primary motor cortex plasticity and dorsal premotor-to-motor
      connectivity in Parkinson's disease.
AB  - We investigated abnormal premotor to motor (PMd-to-M1) connectivity in
      Parkinson's disease (PD) with repetitive transcranial magnetic stimulation
      (rTMS). We studied 28 patients off and on dopaminergic therapy and 28 healthy
      subjects. We delivered 5 Hz rTMS over M1 before and after conditioning PMd with 5
      Hz rTMS. In healthy subjects, motor-evoked potentials (MEPs) elicited by M1-rTMS
      were facilitated and PMd-rTMS left MEPs unchanged. In patients, before PMd-rTMS,
      M1-rTMS induced no MEP facilitation, whereas after PMd-rTMS, it significantly
      facilitated MEPs only when patients were on therapy. In the second experiment, we
      delivered M1-rTMS under 3 different attention-demanding tasks: eyes closed,
      attention directed to the stimulated hand, and attention directed to the
      nonstimulated hand. In healthy subjects, a more pronounced MEP facilitation was
      present when subjects directed attention to the stimulated hand. In patients, the
      MEP facilitation was present when attention was directed to the stimulated hand
      only when patients were on therapy. Finally, we delivered M1-rTMS in patients on
      therapy while they were looking at the stimulated hand, before and after 1 Hz PMd
      rTMS. PMd-rTMS reduced the attention-induced MEP facilitation. We conclude that
      in addition to abnormal M1 plasticity, the reduced MEP facilitation in PD also
      reflects altered PMd-to-M1 connectivity.

PMID- 20051363
TI  - White matter development in adolescence: a DTI study.
AB  - Adolescence is a unique period of physical and cognitive development that
      includes concurrent pubertal changes and sex-based vulnerabilities. While
      diffusion tensor imaging (DTI) studies show white matter maturation throughout
      the lifespan, the state of white matter integrity specific to adolescence is not
      well understood as are the contributions of puberty and sex. We performed whole
      brain DTI studies of 114 children, adolescents, and adults to identify age
      related changes in white matter integrity that characterize adolescence. A
      distinct set of regions across the brain were found to have decreasing radial
      diffusivity across age groups. Region of interest analyses revealed that
      maturation was attained by adolescence in broadly distributed association and
      projection fibers, including those supporting cortical and brain stem integration
      that may underlie known enhancements in reaction time during this period.
      Maturation after adolescence included association and projection tracts,
      including prefrontal-striatal connections, known to support top-down executive
      control of behavior and interhemispheric connectivity. Maturation proceeded in
      parallel with pubertal changes to the postpubertal stage, suggesting hormonal
      influences on white matter development. Females showed earlier maturation of
      white matter integrity compared with males. Together, these findings suggest that
      white matter connectivity supporting executive control of behavior is still
      immature in adolescence.

PMID- 20051364
TI  - Face-identity change activation outside the face system: "release from
      adaptation" may not always indicate neuronal selectivity.
AB  - Face recognition is a complex cognitive process that requires distinguishable
      neuronal representations of individual faces. Previous functional magnetic
      resonance imaging (fMRI) studies using the "fMRI-adaptation" technique have
      suggested the existence of face-identity representations in face-selective
      regions, including the fusiform face area (FFA). Here, we present face-identity
      adaptation findings that are not well explained in terms of face-identity
      representations. We performed blood-oxygen level-dependent (BOLD) fMRI
      measurements, while participants viewed familiar faces that were shown repeatedly
      throughout the experiment. We found decreased activation for repeated faces in
      face-selective regions, as expected based on previous studies. However, we found
      similar effects in regions that are not face-selective, including the
      parahippocampal place area (PPA) and early visual cortex (EVC). These effects
      were present for exact-image (same view and lighting) as well as different-image
      (different view and/or lighting) repetition, but more widespread for exact-image
      repetition. Given the known functional properties of PPA and EVC, it appears
      unlikely that they contain domain-specific face-identity representations.
      Alternative interpretations include general attentional effects and carryover of
      activation from connected regions. These results remind us that fMRI stimulus
      change effects can have a range of causes and do not provide conclusive evidence
      for a neuronal representation of the changed stimulus property.

PMID- 20051365
TI  - Beyond the scalpel: targeting hedgehog in skin cancer prevention.
AB  - This perspective places the article by Tang et al. in this issue of the journal
      (beginning on page 25) in the context of recent work defining the hedgehog
      signaling pathway as a central etiologic factor and as a therapeutic target in
      basal cell cancer. Tang et al. show that inhibition of cyclooxygenase activity,
      either genetically (in a relevant mouse model) or pharmacologically (in the mouse
      and in patients highly predisposed to develop basal cell skin cancers), may
      suppress basal cell carcinogenesis. This new study of cyclooxygenase inhibition,
      together with recent data on the efficacy of hedgehog pathway inhibition, offers
      new hope for patients at a high risk for basal cell cancer.

PMID- 20051366
TI  - Translating cyclooxygenase signaling in patch heterozygote mice into a randomized
      clinical trial in basal cell carcinoma.
AB  - This different perspective on Tang et al. (beginning on p. 25 in this issue of
      the journal) discusses the pivotal role of cyclooxygenase (COX) signaling in the
      pathogenesis of basal cell carcinoma (BCC). These investigators conducted elegant
      experiments showing increased BCC burden in patch heterozygous mice
      overexpressing COX-2 in the epidermis. Genetic deletion of COX-1 or COX-2
      resulted in a robust decrease in BCC burden in patch heterozygote mice. They then
      studied pharmacologic COX inhibition in mice and humans with loss of patch,
      finding a trend in humans toward decreased BCC burden. This finding has
      implications for public health.

PMID- 20051368
TI  - One-hit effects and cancer.
AB  - This perspective on Bellacosa et al. (beginning on p. 48 in this issue of the
      journal) discusses the important biology of microscopically normal tissues in
      carriers of germ-line BRCA1 or BRCA2 mutations. The work of Bellacosa et al. is
      an important step toward discerning which pathways may be altered when one BRCA
      allele is inactivated.

PMID- 20051367
TI  - Targeting ornithine decarboxylase for the prevention of nonmelanoma skin cancer
      in humans.
AB  - Bailey et al. report in this issue of the journal (beginning on page 35) one of
      the first successful trials of basal cell carcinoma (BCC) prevention. Oral alpha
      difluoromethyl-dl-ornithine (DFMO) reduced new BCCs in patients with a prior
      history of nonmelanoma skin cancer. DFMO is an inhibitor of ornithine
      decarboxylase, a key enzyme in the polyamine biosynthetic pathway. This
      perspective on Bailey et al. discusses our knowledge of the contribution of
      polyamines to BCC pathogenesis, how this knowledge advanced the development of a
      new method to prevent BCCs, and prospects for future studies of DFMO in BCC
      prevention.

PMID- 20051369
TI  - Strategic approach to validating methylated genes as biomarkers for breast
      cancer.
AB  - Although the potential of biomarkers to aid in the early detection, diagnosis,
      prevention, and treatment of breast cancer is broadly recognized and numerous
      biomarker candidates have been reported in the literature, few molecular markers
      have been adopted into clinical use to date. To address this lack of translation
      of biomarkers from the bench to clinical practice, the Cancer Biomarkers Research
      Group in the Division of Cancer Prevention of the National Cancer Institute
      organized a meeting, "Strategic Discussion on Biomarkers for Breast Cancer,"
      which was held at the Fred Hutchinson Cancer Research Center on September 14,
      2008. Participants included industry leaders, basic and physician scientists, and
      National Cancer Institute program staff. The objectives of this strategic
      discussion were to define clinical uses and needed performance characteristics of
      biomarkers; to identify novel approaches to discover and validate breast cancer
      biomarkers, particularly those with improved chances of being clinically useful;
      and to identify candidate DNA methylation markers that could be taken forward for
      validation. Participants presented and recommended methylation biomarkers
      suitable for initiating collaborative projects to evaluate the markers for future
      clinical application. This commentary summarizes their discussions and
      recommendations and the rationale for initiating specific projects to validate
      DNA methylation biomarkers of breast cancer.

PMID- 20051370
TI  - Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in
      genetically predisposed PTCH1+/- humans and mice.
AB  - In vitro and epidemiologic studies favor the efficacy of nonsteroidal anti
      inflammatory drugs (NSAID) in preventing skin squamous photocarcinogenesis, but
      there has been relatively little study of their efficacy in preventing the more
      common skin basal cell carcinoma (BCC) carcinogenesis. We first compared the
      relative anti-BCC effects of genetic deletion and NSAID pharmacologic inhibition
      of cyclooxygenase (COX) enzymes in the skin of Ptch1(+/-) mice. We then assessed
      the effects of celecoxib on the development of BCCs in a 3-year, double-blinded,
      randomized clinical trial in 60 (PTCH1(+/-)) patients with the basal cell nevus
      syndrome. In Ptch1(+/-) mice, genetic deletion of COX1 or COX2 robustly decreased
      (75%; P < 0.05) microscopic BCC tumor burden, but pharmacologic inhibition with
      celecoxib reduced microscopic BCCs less efficaciously (35%; P < 0.05). In the
      human trial, we detected a trend for oral celecoxib reducing BCC burden in all
      subjects (P = 0.069). Considering only the 60% of patients with less severe
      disease (<15 BCCs at study entry), celecoxib significantly reduced BCC number and
      burden: subjects receiving placebo had a 50% increase in BCC burden per year,
      whereas subjects in the celecoxib group had a 20% increase (P(difference) =
      0.024). Oral celecoxib treatment inhibited BCC carcinogenesis in PTCH1(+/-) mice
      and had a significant anti-BCC effect in humans with less severe disease.

PMID- 20051371
TI  - A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention
      study of {alpha}-difluoromethylornithine in subjects with previous history of
      skin cancer.
AB  - Preclinical studies have shown that the inhibition of ornithine decarboxylase
      (ODC) by alpha-difluoromethylornithine (DFMO) and resultant decreases in tissue
      concentrations of polyamines (putrescine and spermidine) prevents neoplastic
      developments in many tissue types. Clinical studies of oral DFMO at 500
      mg/m(2)/day revealed it to be safe and tolerable and resulted in significant
      inhibition of phorbol ester-induced skin ODC activity. Two hundred and ninety-one
      participants (mean age, 61 years; 60% male) with a history of prior nonmelanoma
      skin cancer (NMSC; mean, 4.5 skin cancers) were randomized to oral DFMO (500
      mg/m(2)/day) or placebo for 4 to 5 years. There was a trend toward a history of
      more prior skin cancers in subjects randomized to placebo, but all other
      characteristics including sunscreen and nonsteroidal anti-inflammatory drug use
      were evenly distributed. Evaluation of 1,200 person-years of follow-up revealed a
      new NMSC rate of 0.5 events/person/year. The primary end point, new NMSCs, was
      not significantly different between subjects taking DFMO and placebo (260 versus
      363 cancers, P = 0.069, two-sample t test). Evaluation of basal cell (BCC) and
      squamous cell cancers separately revealed very little difference in squamous cell
      cancer between treatment groups but a significant difference in new BCC (DFMO,
      163 cancers; placebo, 243 cancers; expressed as event rate of 0.28
      BCC/person/year versus 0.40 BCC/person/year, P = 0.03). Compliance with DFMO was
      >90% and it seemed to be well tolerated with evidence of mild ototoxicity as
      measured by serial audiometric examination when compared with placebo subjects.
      The analysis of normal skin biopsies revealed a significant (P < 0.05) decrease
      in 12-0-tetradecanoylphorbol-13-acetate-induced ODC activity (month 24, 36, and
      48) and putrescine concentration (month 24 and 36 only) in DFMO subjects.
      Subjects with a history of skin cancer taking daily DFMO had an insignificant
      reduction (P = 0.069) in new NMSC that was predominantly due to a marked
      reduction in new BCC. Based on these data, the potential of DFMO, alone or in
      combination, to prevent skin cancers should be explored further.

PMID- 20051372
TI  - Altered gene expression in morphologically normal epithelial cells from
      heterozygous carriers of BRCA1 or BRCA2 mutations.
AB  - We hypothesized that cells bearing a single inherited "hit" in a tumor suppressor
      gene express an altered mRNA repertoire that may identify targets for measures
      that could delay or even prevent progression to carcinoma. We report here on the
      transcriptomes of primary breast and ovarian epithelial cells cultured from BRCA1
      and BRCA2 mutation carriers and controls. Our comparison analyses identified
      multiple changes in gene expression, in both tissues for both mutations, which
      were validated independently by real-time reverse transcription-PCR analysis.
      Several of the differentially expressed genes had been previously proposed as
      cancer markers, including mammaglobin in breast cancer and serum amyloid in
      ovarian cancer. These findings show that heterozygosity for a mutant tumor
      suppressor gene can alter the expression profiles of phenotypically normal
      epithelial cells in a gene-specific manner; these detectable effects of "one hit"
      represent early molecular changes in tumorigenesis that may serve as novel
      biomarkers of cancer risk and as targets for chemoprevention.

PMID- 20051373
TI  - Chemoprevention of cigarette smoke-induced alterations of MicroRNA expression in
      rat lungs.
AB  - We previously showed that exposure to environmental cigarette smoke (ECS) for 28
      days causes extensive downregulation of microRNA expression in the lungs of rats,
      resulting in the overexpression of multiple genes and proteins. In the present
      study, we evaluated by microarray the expression of 484 microRNAs in the lungs of
      either ECS-free or ECS-exposed rats treated with the orally administered
      chemopreventive agents N-acetylcysteine, oltipraz, indole-3-carbinol, 5,6
      benzoflavone, and phenethyl isothiocyanate (as single agents or in combinations).
      This is the first study of microRNA modulation by chemopreventive agents in
      nonmalignant tissues. Scatterplot, hierarchical cluster, and principal component
      analyses of microarray and quantitative PCR data showed that none of the above
      chemopreventive regimens appreciably affected the baseline microRNA expression,
      indicating potential safety. On the other hand, all of them attenuated ECS
      induced alterations but to a variable extent and with different patterns,
      indicating potential preventive efficacy. The main ECS-altered functions that
      were modulated by chemopreventive agents included cell proliferation, apoptosis,
      differentiation, Ras activation, P53 functions, NF-kappaB pathway, transforming
      growth factor-related stress response, and angiogenesis. Some microRNAs known to
      be polymorphic in humans were downregulated by ECS and were protected by
      chemopreventive agents. This study provides proof-of-concept and validation of
      technology that we are further refining to screen and prioritize potential agents
      for continued development and to help elucidate their biological effects and
      mechanisms. Therefore, microRNA analysis may provide a new tool for predicting at
      early carcinogenesis stages both the potential safety and efficacy of cancer
      chemopreventive agents.

PMID- 20051374
TI  - Overexpression of cyclooxygenase-2 in rat oral cancers and prevention of oral
      carcinogenesis in rats by selective and nonselective COX inhibitors.
AB  - Oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide (NQO)
      show substantial overexpression of cyclooxygenase-2 (COX-2) when compared with
      adjacent phenotypically normal oral tissues. By contrast, neither 5-lipoxygenase
      (LOX) nor 12-LOX is overexpressed in rat oral cancers. Two chemoprevention
      studies were done to test the resulting hypothesis that COX-2 is a useful target
      for oral cancer chemoprevention in the rat. In both studies, male F344 rats
      received drinking water exposure to NQO (20 ppm) for 10 weeks, followed by
      administration of chemopreventive agents from week 10 until study termination at
      week 26. In the first study, groups of rats were fed basal diet (control), or
      basal diet supplemented with the selective COX-2 inhibitor celecoxib (500 or
      1,500 mg/kg diet), the nonselective COX inhibitor piroxicam (50 or 150 mg/kg
      diet), or the 5-LOX inhibitor zileuton (2,000 mg/kg diet). In the second study,
      rats were fed basal diet (control) or basal diet supplemented with nitric oxide
      naproxen (180 or 90 mg/kg diet), a nonselective COX inhibitor that shows reduced
      gastrointestinal toxicity. When compared with dietary controls, celecoxib
      decreased oral cancer incidence, cancer invasion score, and cancer-related
      mortality. Piroxicam decreased cancer-related mortality and cancer invasion
      score, whereas nitric oxide-naproxen decreased oral cancer incidence and cancer
      invasion score. By contrast, zileuton showed no chemopreventive activity by any
      parameter assessed. These data show that both selective and nonselective
      inhibitors of COX-2 can prevent NQO-induced oral carcinogenesis in rats. The
      chemopreventive activity of COX inhibitors may be linked to overexpression of
      their enzymatic target in incipient oral neoplasms.

PMID- 20051375
TI  - Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against
      rat colon carcinogenesis and inhibition of human colon cancer cell growth.
AB  - Sea cucumber extracts have been widely used to treat individuals with
      inflammatory conditions in East Asia. The present study has been designed to test
      potential colon cancer-preventive properties of Frondanol A5, a glycolipid
      extract from the sea cucumber, Cucumaria frondosa, using in vivo and in vitro
      models of colon cancer. Chemopreventive efficacy of Frondanol A5 was evaluated on
      azoxymethane-induced rat colon carcinogenesis using colonic aberrant crypt foci
      (ACF) as efficacy marker. At 7 weeks of age, groups of rats (12 per group) were
      fed the AIN-76A diet, and ACFs were induced by azoxymethane (15 mg/kg body
      weight). Three days after azoxymethane treatment, rats were fed with the diets
      containing 0, 150, and 450 ppm of Frondanol A5 and continued on the diets for 8
      weeks, at which time ACFs were evaluated. Expression levels of proliferating cell
      nuclear antigen and p21(WAF1/CIP1) were determined in ACFs. Further, Frondanol A5
      (10-120 microg/mL) was studied for its growth-inhibitory and apoptotic effects in
      the HCT-116 cell line. Dietary administration of 150 and 450 ppm of Frondanol A5
      significantly suppressed azoxymethane-induced total colonic ACF formation,
      approximately 34% to 55% (P < 0.01 to P < 0.0001), and multicrypt aberrant foci
      (48-68.5%, P < 0.0001) in a dose-dependent manner. ACFs in rats treated with
      Frondanol A5 showed significant upregulation of p21(WAF1/CIP1) and downregulation
      of proliferating cell nuclear antigen compared with control group. Frondanol A5
      showed growth inhibition at S and G(2)-M phase with a decrease in Cdc25c and an
      increase in p21(WAF1/CIP) with significant apoptosis associated with H2AX
      phosphorylation and caspase-2 cleavage in HCT116 cells. Overall, Frondanol A5
      exhibits potential chemopreventive properties for colon carcinogenesis, which
      suggests further development of this sea cucumber extract.

PMID- 20051376
TI  - Folate deficiency alters hepatic and colon MGMT and OGG-1 DNA repair protein
      expression in rats but has no effect on genome-wide DNA methylation.
AB  - Folate deficiency is implicated in human colon cancer. The effects of feeding
      rats a folate-deficient diet for 24 weeks on DNA damage (8-oxo-7,8
      dihydroguanine), DNA repair [O(6)-methylguanine-DNA methyltransferase (MGMT) and
      8-oxoguanine-DNA glycosylase (OGG-1) activity], and epigenetic parameters (genome
      wide cytosine methylation and indices of cellular methylation status) were
      investigated. Relative to control diet, the folate-deficient diet resulted in
      significantly reduced levels of serum ( approximately 80%; P < 0.0001), whole
      blood ( approximately 40%; P < 0.0001), and tissue folate (between 25% and 60%
      depending on the tissue sampled; P < 0.05); increased plasma total homocysteine (
      approximately 35%; P < 0.05); and decreased S-adenosylmethionine to S
      adenosylhomocysteine concentrations ( approximately 11%; P < 0.05). There was no
      significant change in the levels of 5-methyldeoxycytidine in liver or colon DNA,
      nor in the activity of liver DNA cytosine methyltransferase. However, there were
      significant increases in 8-oxo-7,8-dihydroguanine (P < 0.001) in lymphocyte DNA
      and in levels of the DNA repair proteins OGG-1 ( approximately 27%; P < 0.03) and
      MGMT ( approximately 25%; P < 0.003) in the liver, but not in the colon. This may
      reflect the ability of the liver, but not the colon, to upregulate DNA repair
      enzymes in response to either elevated DNA damage or an imbalance in the
      nucleotide precursor pool. These results show that folate deficiency can
      significantly modulate DNA damage and DNA repair, providing mechanisms by which
      it plays a role in the etiology of human cancer. We speculate that the inability
      of colon tissue to respond to folate deficiency occurs in humans and may increase
      the potential for malignant transformation.

PMID- 20051377
TI  - Sulindac and sulindac metabolites in nipple aspirate fluid and effect on drug
      targets in a phase I trial.
AB  - Regular use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated
      with reduced risk of breast cancer. Sulindac, a nonselective NSAID with both
      cyclooxygenase-2-dependent and -independent activities, is a candidate for breast
      chemoprevention. We conducted a phase Ib trial in 30 women at increased risk for
      breast cancer to evaluate the breast tissue distribution of sulindac at two dose
      levels (150 mg daily and 150 mg twice daily for 6 weeks), using nipple aspirate
      fluid (NAF) as a surrogate of breast tissue drug exposure. We also explored the
      effect of sulindac on drug-induced biomarkers in NAF. We show that sulindac and
      its metabolites partition to human breast as measured by NAF levels. Sulindac
      intervention did not decrease 13,14-dihydro-15-keto prostaglandin A(2), a stable
      derivative of prostaglandin E(2), in NAF, but exposure was associated with a
      significant trend towards higher levels of growth differentiation factor 15 in
      NAF in women receiving 150 mg twice daily (P = 0.038). These results are the
      first to show partitioning of sulindac and metabolites to human breast tissue and
      the first evidence for a potential dose-dependent effect of sulindac on growth
      differentiation factor 15 levels in NAF.

PMID- 20051378
TI  - Pomegranate ellagitannin-derived compounds exhibit antiproliferative and
      antiaromatase activity in breast cancer cells in vitro.
AB  - Estrogen stimulates the proliferation of breast cancer cells and the growth of
      estrogen-responsive tumors. The aromatase enzyme, which converts androgen to
      estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a
      rich source of ellagitannins (ET), has attracted recent attention due to its
      anticancer and antiatherosclerotic properties. On consumption, pomegranate ETs
      hydrolyze, releasing ellagic acid, which is then converted to 3,8-dihydroxy-6H
      dibenzo[b,d]pyran-6-one ("urolithin") derivatives by gut microflora. The purpose
      of this study was to investigate the antiaromatase activity and inhibition of
      testosterone-induced breast cancer cell proliferation by ET-derived compounds
      isolated from pomegranates. A panel of 10 ET-derived compounds including ellagic
      acid, gallagic acid, and urolithins A and B (and their acetylated, methylated,
      and sulfated analogues prepared in our laboratory) were examined for their
      ability to inhibit aromatase activity and testosterone-induced breast cancer cell
      proliferation. Using a microsomal aromatase assay, we screened the panel of ET
      derived compounds and identified six with antiaromatase activity. Among these,
      urolithin B (UB) was shown to most effectively inhibit aromatase activity in a
      live cell assay. Kinetic analysis of UB showed mixed inhibition, suggesting more
      than one inhibitory mechanism. Proliferation assays also determined that UB
      significantly inhibited testosterone-induced MCF-7aro cell proliferation. The
      remaining test compounds also exhibited antiproliferative activity, but to a
      lesser degree than UB. These studies suggest that pomegranate ET-derived
      compounds have potential for the prevention of estrogen-responsive breast
      cancers.

PMID- 20051379
TI  - Atorvastatin and celecoxib in combination inhibits the progression of androgen
      dependent LNCaP xenograft prostate tumors to androgen independence.
AB  - Epidemiology studies suggest that statins and nonsteroidal anti-inflammatory
      drugs reduce the risk of prostate cancer. In the present study, LNCaP cells were
      cultured in regular medium containing fetal bovine serum or in medium
      supplemented with charcoal-stripped fetal bovine serum to mimic androgen
      deprivation treatment. We found that atorvastatin (Lipitor) or celecoxib
      (Celebrex) treatment of LNCaP cells cultured in regular or androgen-depleted
      medium inhibited growth and stimulated apoptosis. A combination of atorvastatin
      and celecoxib was more effective than either agent alone. In animal studies,
      severe combined immunodeficient mice were injected s.c. with LNCaP cells in
      Matrigel. After 4 to 6 weeks, mice with LNCaP tumors (about 0.6 cm wide and 0.6
      cm long) were surgically castrated and received daily i.p. injections of vehicle,
      atorvastatin (10 microg/g body weight/d), celecoxib (10 microg/g/d), or a
      combination of atorvastatin (5 microg/g/d) and celecoxib (5 microg/g/d) for 42
      days. In all groups, the androgen-dependent LNCaP tumors regressed initially in
      response to castration, but the tumors eventually progressed to androgen
      independence and started to grow. Treatment of the mice with atorvastatin or
      celecoxib alone suppressed the regrowth of LNCaP tumors after castration. A
      combination of low doses of atorvastatin and celecoxib had a more potent effect
      in inhibiting the growth and progression of LNCaP tumors to androgen independence
      than a higher dose of either agent alone. Our results indicate that
      administration of a combination of atorvastatin and celecoxib may be an effective
      strategy for the prevention of prostate cancer progression from androgen
      dependence to androgen independence.

PMID- 20051381
TI  - Two-color fluorescence labeling in acrolein-fixed brain tissue.
AB  - Acrolein is a potent fixative that provides both excellent preservation of
      ultrastructural morphology and retention of antigenicity, thus it is frequently
      used for immunocytochemical detection of antigens at the electron microscopic
      level. However, acrolein is not commonly used for fluorescence microscopy because
      of concerns about possible autofluorescence and destruction of the luminosity of
      fluorescent dyes. Here we describe a simple protocol that allows fine
      visualization of two fluorescent markers in 40-mum sections from acrolein
      perfused rat brain. Autofluorescence was removed by pretreatment with 1% sodium
      borohydride for 30 min, and subsequent incubation in a 50% ethanol solution
      containing 0.3% hydrogen peroxide enhanced fluorescence labeling. Thus,
      fluorescence labeling can be used for high-quality detection of markers in tissue
      perfused with acrolein. Furthermore, adjacent acrolein-fixed sections from a
      single experiment can be processed to produce high-quality results for electron
      microscopy or fluorescence labeling.

PMID- 20051380
TI  - Identification of markers for newly formed beta-cells in the perinatal period: a
      time of recognized beta-cell immaturity.
AB  - Markers of beta-cell maturity would be useful in staging the differentiation of
      stem/progenitor cells to beta-cells whether in vivo or in vitro. We previously
      identified markers for newly formed beta-cells in regenerating rat pancreases
      after 90% partial pancreatectomy. To test the generality of these markers of
      newly formed beta-cells, we examined their expression during the perinatal
      period, a time of recognized beta-cell immaturity. We show by semiquantitative RT
      PCR and immunostaining over the time course from embryonic day 18/20 to birth, 1
      day, 2 days, 3 days, 7 days, and adult that MMP-2, CK-19, and SPD are truly
      markers of new and immature beta-cells and that their expression transiently
      peaks in the perinatal period and is not entirely synchronous. The shared
      expression of these markers among fetal, newborn, and newly regenerated beta
      cells, but not adult, strongly supports their use as potential markers for new
      beta-cells in the assessment of both the maturity of stem cell-derived insulin
      producing cells and the presence of newly formed islets (neogenesis) in the adult
      pancreas.

PMID- 20051382
TI  - Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated
      protein kinase and activating transcription factor 2 in HEK293 cells expressing
      GPR55 and IM-9 lymphoblastoid cells.
AB  - Lysophosphatidylinositol (LPI) is an endogenous ligand for GPR55, a putative
      novel type of cannabinoid receptor. In this study, we first examined the effects
      of LPI on p38 mitogen-activated protein kinase in HEK293 cells expressing GPR55.
      LPI induced the rapid phosphorylation of p38 mitogen-activated protein kinase in
      GPR55-expressing cells. No apparent effect was observed in the vector-transfected
      cells. The exposure of GPR55-expressing cells to LPI also triggered the
      phosphorylation of activating transcription factor 2 downstream of the p38
      mitogen-activated protein kinase. Treatment of the cells with Y-27632 [a Rho
      associated kinase (ROCK) inhibitor] blocked the LPI-induced phosphorylation of
      p38 mitogen-activated protein kinase and activating transcription factor 2,
      suggesting that the Rho-ROCK pathway is involved in these cellular responses.
      Notably, GPR55 was found to be abundantly expressed in lymphoid organs such as
      the spleen and thymus. We obtained evidence that rapid phosphorylation of p38
      mitogen-activated protein kinase and activating transcription factor 2 also takes
      place in IM-9 lymphoblastoid cells, which naturally express GPR55, after
      stimulation with LPI. These results suggest that GPR55 and its endogenous ligand
      LPI play essential roles in the homoeostatic responses to stress signals in
      several mammalian tissues and cells including certain types of immune cells.

PMID- 20051383
TI  - Characterization of site-specific mutants of alkylhydroperoxide reductase with
      dual functionality from Helicobacter pylori.
AB  - Alkylhydroperoxide reductase (AhpC) is an abundant and important antioxidant
      protein present in Helicobacter pylori (HP), a spiral Gram-negative
      microaerophilic bacterium. By sequence alignment and structure comparison, HP
      AhpC was found to be more homologous to human peroxiredoxins (hPrx) than to other
      eubacterial AhpC proteins. Similar to hPrxI, native HP-AhpC existed as a dimer of
      single subunit, comprising alpha-helix and beta-sheet domains with low surface
      hydrophobicity. AhpC can form high-molecular-weight (HMW) aggregates ranging from
      700 to higher than 2,000 kDa under oxidative stress, possessing chaperone
      activity in the presence of thioredoxin (Trx). Further analysis of peroxide
      reductase activities showed that HP-AhpC was more resistant to H(2)O(2) than
      hPrxI. However, the mechanism of enzyme inactivation to H(2)O(2) appeared to be
      similar for both HP-AhpC and hPrxI as revealed by native gel electrophoresis
      followed by proteomic identification using two-dimensional gel electrophoresis (2
      DE) and LC-MS/MS. In contrast to T90D-hPrxI mutant with chaperone activity, site
      specific mutant T87D-HP-AhpC did not form HMW chaperone complexes. The comparison
      of these two evolutionarily distant and yet functionally related enzymes may shed
      some light on the mechanism(s) underlying the evolution and development of the
      dual functionality in HP-AhpC and hPrxI with similar protein structure.

PMID- 20051384
TI  - Inactivation of the tumour suppressor, PTEN, in smooth muscle promotes a pro
      inflammatory phenotype and enhances neointima formation.
AB  - AIMS: Phosphatase and tensin homolog (PTEN) is implicated as a negative regulator
      of vascular smooth muscle cell (SMC) proliferation and injury-induced vascular
      remodelling. We tested if selective depletion of PTEN only in SMC is sufficient
      to promote SMC phenotypic modulation, cytokine production, and enhanced neointima
      formation. METHODS AND RESULTS: Smooth muscle marker expression and induction of
      pro-inflammatory cytokines were compared in cultured SMC expressing control or
      PTEN-specific shRNA. Compared with controls, PTEN-deficient SMC exhibited
      increased phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian
      target of rapamycin (mTOR) signalling and nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) activity, reduced expression of SM
      markers (SM-alpha-actin and calponin), and increased production of stromal cell
      derived factor-1alpha (SDF-1alpha), monocyte chemotactic protein-1 (MCP-1),
      interleukin-6 (IL-6), and chemokine (C-X-C motif) ligand 1 (KC/CXCL1) under basal
      conditions. PI3K/Akt or mTOR inhibition reversed repression of SM marker
      expression, whereas PI3K/Akt or NF-kappaB inhibition blocked cytokine induction
      mediated by PTEN depletion. Carotid ligation in mice with genetic reduction of
      PTEN specifically in SMC (SMC-specific PTEN heterozygotes) resulted in enhanced
      neointima formation, increased SMC hyperplasia, reduced SM-alpha-actin and
      calponin expression, and increased NF-kappaB and cytokine expression compared
      with wild-types. Lesion formation in SMC-specific heterozygotes was similar to
      lesion formation in global PTEN heterozygotes, indicating that inactivation of
      PTEN exclusively in SMC is sufficient to induce considerable increases in
      neointima formation. CONCLUSION: PTEN activation specifically in SMC is a common
      upstream regulator of multiple downstream events involved in pathological
      vascular remodelling, including proliferation, de-differentiation, and production
      of multiple cytokines.

PMID- 20051385
TI  - Cystathionine gamma-lyase deficiency and overproliferation of smooth muscle
      cells.
AB  - AIMS: Cystathionine gamma-lyase (CSE)-derived H2S plays an important role in
      regulating cell growth. Lack of CSE expression results in development of
      hypertension. The current study compared proliferation of smooth muscle cells
      derived from CSE gene knockout mice (SMCs-KO) with that of wild-type mice (SMCs
      WT). METHODS AND RESULTS: Cell proliferation was assessed by bromodeoxyuridine
      incorporation. Gene expression was analysed by western blotting, real-time PCR,
      and microarray analysis. Enhanced cell proliferation was detected in SMCs-KO and
      in the media of the aorta from CSE KO mice. SMCs-KO underwent significantly more
      apoptosis than SMCs-WT when treated with exogenous H2S (100 microM). CSE KO mice
      showed much lower level of phosphorylated extracellular signal-regulated kinase
      (ERK1/2) in mesentery arteries compared with those of WT mice, and exogenous H2S
      induced more phosphorylation of ERK1/2 in SMCs-KO compared with that in SMCs-WT.
      Decreased p21(Cip/WAF-1) but increased cyclin D1 expression was observed in
      isolated SMCs and vascular tissues from CSE KO mice, and exogenous H2S caused
      more increase in p21(Cip/WAF-1) expression and more decrease in cyclin D1
      expression in SMCs-KO than in SMCs-WT. The transcriptional expression of
      calcitonin receptor-like, intergrin beta 1, and heparin-binding epidermal growth
      factor-like growth factor was also significantly increased in the aorta of CSE KO
      mice. CONCLUSION: SMCs-KO display an increased proliferation rate in vitro and in
      vivo, and these cells are more susceptible to apoptosis induced by exogenous H2S
      at physiologically relevant concentrations. These cellular effects of H2S are
      mediated by phosphorylation of ERK1/2 and altered expression of cyclin D1 and
      p21(Cip/WAF-1).

PMID- 20051386
TI  - Cardiomyocyte proliferation: paving the way for cardiac regenerative medicine
      without stem cell transplantation.

PMID- 20051388
TI  - Glycosphingolipids as mediators of phenotypic changes associated with development
      and cancer progression.
AB  - Sen-itiroh Hakomori has been involved for the past approximately 40 years in
      studies on structure and function of glycosphingolipids (GSLs). The following is
      a brief summary of highlights of his research, performed in association with his
      colleagues.

PMID- 20051389
TI  - Akira Kobata: a man who established the structural basis for glycobiology of N
      linked sugar chains.
AB  - Akira Kobata is a pioneer of the glycobiology of N-linked sugar chains. He
      established the basis of glycobiology by developing a series of reliable methods
      to analyse the structures of N-linked sugar chains. The sensitive methods
      established by him greatly contributed to our understanding of the structural
      characteristics of the sugar chains and the biosynthetic mechanisms responsible
      for the production of such characteristics. He also provided new aspects that the
      sugar chains of glycoproteins play an important role in cell-to-cell recognition,
      and that the structures of sugar chains are altered under physiological and
      pathological conditions, including many tumours and diseases on a structural
      basis. In this article, the author would like to sketch out Kobata's main
      contributions to glycobiology for the sake of young scientists, who are planning
      to enter this scientific field in the future.

PMID- 20051395
TI  - Anticholinergic drugs for the treatment of COPD are safe... are they?

PMID- 20051396
TI  - Primary vs metastatic pulmonary adenocarcinoma: toward a fuller understanding of
      truth.

PMID- 20051397
TI  - PET scans for lung nodules: costs and cost-effectiveness.

PMID- 20051398
TI  - Improving procedural training and certification in pulmonary medicine.

PMID- 20051399
TI  - Primary care, specialist care, and chronic care: can they interlock?

PMID- 20051400
TI  - Is there room for specialists in the patient-centered medical home?

PMID- 20051402
TI  - Targeting primary afferent nerves for novel antitussive therapy.
AB  - The best available data support the hypothesis that there are at least two types
      of vagal nerves responsible for initiating coughing reflexes. One type of nerve
      conducts action potentials in the A-range and is characterized by rapidly
      adapting responses to mechanical probing or acidification of the large airway
      epithelium. Stimulation of these nerves can evoke cough in unconscious
      experimental animals and humans. These nerves are important in immediate cough
      evoked by aspiration and as such perform a critical role in airway defense. The
      other type of primary afferent nerve involved in cough is the vagal C-fiber.
      Inhalation of selective C-fiber stimulants leads to cough only in conscious
      animals. In clinical studies, inhalation of a low concentration of a C-fiber
      stimulant causes an irritating, itchy urge-to-cough sensation that mimics the
      urge-to-cough sensations associated with respiratory tract infection, post
      infection, gastroesophageal reflux disorders, and inflammatory airway diseases.
      Here we discuss the recent advances in sensory neurobiology that allow for the
      targeting of vagal C-fibers for novel antitussive therapy. No attempts are made
      to be all-inclusive with respect to the numerous possible molecular targets being
      considered to accomplish this goal. Rather, two general strategies are discussed:
      decreasing generator potential amplitude and decreasing the efficiency by which a
      generator potential evokes action-potential discharge. For the first category we
      focus on two targets, transient receptor potential vanilloid 1 and transient
      receptor potential A1. For the latter category we focus on recent advances in
      voltage-gated sodium (Na(V)) channel biology.

PMID- 20051403
TI  - Coagulopathy in critically ill patients: part 2-soluble clotting factors and
      hemostatic testing.
AB  - This manuscript provides an overview of how to interpret in vitro clotting
      studies and how to select studies to evaluate patients with bleeding disorders in
      the ICU. It provides a practical approach to understanding the complex subject of
      clotting factor abnormalities, including the most common problems of
      preanalytical error and anticoagulation therapy. Limitations and pitfalls of
      diagnostic testing are highlighted.

PMID- 20051404
TI  - An approach to interventional pulmonary fellowship training.
AB  - Interventional pulmonology continues to be a specialty that is experiencing an
      evolution of new technologies, with an emphasis on multidisciplinary care. The
      diversity and application of these procedures in patients with more complex
      conditions is leading to the need for more specific recommendations in training
      within this area. As patient safety and outcomes-based measures of clinical
      practice and procedures are in the forefront, the need for standardization in
      procedural training in high-volume centers of excellence beyond pulmonary and
      critical care fellowships must be considered. Other procedure-based specialties
      have developed such training programs, with structured curricula to enhance
      patient safety and outcomes, develop validated metrics for competency assessment
      of trainees, improve trainee education, and further advance the field by
      fostering research.

PMID- 20051405
TI  - Pulmonary vein stenosis following left pneumonectomy: a variant contributor to
      postpneumonectomy syndrome.
AB  - Postpneumonectomy syndrome is a recognized complication following pneumonectomy,
      resulting from mediastinal displacement into the vacated pleural space.
      Mediastinal displacement causes bronchial compression and dyspnea. This report
      describes a 47-year-old woman who presented with shortness of breath 6 months
      after a left pneumonectomy. She was initially hypoxic and was found to have a
      patent foramen ovale. Following closure of the patent foramen ovale, she was no
      longer hypoxic, but she continued to have dyspnea with exertion and left lateral
      decubitus positioning. There was no evidence of bronchial compression, but MRI
      and transesophageal echocardiography suggested pulmonary vein compression due to
      mediastinal displacement. Transthoracic echocardiography confirmed functional
      pulmonary vein compression that was worse in the standing and in the left lateral
      positions. Her symptoms improved with mediastinal repositioning using a
      transesophageal echocardiography-guided approach. Positional pulmonary vein
      compression may be an underdiagnosed complication of pneumonectomy.

PMID- 20051406
TI  - Hyponatremia in pulmonary TB: evidence of ectopic antidiuretic hormone
      production.
AB  - Hyponatremia is among the most common biochemical abnormalities in hospital
      inpatients. The syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      is one of several causes of hyponatremia, particularly in patients with pulmonary
      diseases. The mechanism of SIADH associated with pulmonary infection is, however,
      poorly understood. We report an unusual case of hyponatremia in a man with
      pulmonary TB and central diabetes insipidus with biochemical evidence of ectopic
      antidiuretic hormone production as a possible mechanism causing hyponatremia.

PMID- 20051407
TI  - Complications of massive transfusion.
AB  - Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock, but can
      be associated with significant complications. The lethal triad of acidosis,
      hypothermia, and coagulopathy associated with MT is associated with a high
      mortality rate. Other complications include hypothermia, acid/base derangements,
      electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia,
      hyperkalemia), citrate toxicity, and transfusion-associated acute lung injury.
      Blood transfusion in trauma, surgery, and critical care has been identified as an
      independent predictor of multiple organ failure, systemic inflammatory response
      syndrome, increased infection, and increased mortality in multiple studies. Once
      definitive control of hemorrhage has been established, a restrictive approach to
      blood transfusion should be implemented to minimize further complications.

PMID- 20051408
TI  - The committee on publication ethics flowcharts.

PMID- 20051409
TI  - A 41-year-old woman with AIDS and recurrent pneumonia.

PMID- 20051410
TI  - A 62-year-old woman with chronic cough and bronchospasm.

PMID- 20051413
TI  - Why look for artifacts alone when the original is visible?

PMID- 20051414
TI  - Caution advised with use of fospropofol.

PMID- 20051415
TI  - Endobronchial ultrasonography-guided transbronchial needle aspiration in patients
      with suspected sarcoidosis.

PMID- 20051416
TI  - Endobronchial ultrasonography vs conventional transbronchial needle aspiration in
      the diagnosis of sarcoidosis.

PMID- 20051417
TI  - Oral hygiene and nosocomial pneumonia in critically ill patients.

PMID- 20051418
TI  - Resolving conflicts with surrogate decision makers.

PMID- 20051419
TI  - Rescue treatment in asthma.

PMID- 20051420
TI  - Severity of illness and outcome in patients with end-stage idiopathic pulmonary
      fibrosis requiring mechanical ventilation.

PMID- 20051421
TI  - Accuracy in identifying podiatric surgeries.

PMID- 20051422
TI  - Specificity of a quantitative real-time polymerase chain reaction assay for the
      detection of invasive pneumococcal disease: identifying streptococcus pneumoniae
      using quantitative polymerase chain reaction.

PMID- 20051423
TI  - Combining blood flow and tissue Doppler imaging with N-terminal pro-type B
      natriuretic peptide for risk stratification of clinically stable patients with
      systolic heart failure.
AB  - AIMS: This study was designed to ascertain whether the combination of Doppler
      assessment of the ratio of mitral blood flow to myocardial early diastolic
      velocities (E/E(m) ratio) and plasma N-terminal pro-type B natriuretic peptide
      (NT-proBNP) testing is useful to better stratify patients with stable systolic
      heart failure (HF). METHODS AND RESULTS: A total of 362 outpatients with chronic
      systolic HF (left ventricular ejection fraction <or=45%) underwent clinical
      assessment, NT-proBNP testing, and comprehensive echo-Doppler study. The endpoint
      was all-cause mortality or HF-related hospital admissions (i.e. hospitalization
      for worsening HF, biventricular pacemaker implantation, or mitral valve surgery).
      Median follow-up duration was 25 months. Two hundred and fifty-nine patients were
      judged clinically stable by a Framingham's criteria-based HF score. In
      multivariate Cox's proportional hazards analysis, plasma NT-proBNP (P< 0.0001)
      and E/E(m) ratio (P= 0.04) were among the significant predictors of the combined
      endpoint. Survival free from cardiac mortality and HF-related hospitalization was
      55% in patients with the E/E(m) ratio in the higher third (>or=12), 77% in those
      with the E/E(m) ratio in the intermediate third, and 86% in those with the E/E(m)
      ratio in the lower third (<or=7) (P< 0.0001). By stratifying patients according
      to NT-proBNP above the median, patients' outcome was predicted in 13 out of 17 in
      the intermediate third (P = 0.002) and in 9 out of 10 in the lower third of
      E/E(m) ratio (P= 0.005). CONCLUSION: In patients with stable HF categorized
      according to the E/E(m) ratio, NT-proBNP testing improves risk stratification,
      particularly in those with minor degrees of diastolic dysfunction.

PMID- 20051424
TI  - Right ventricular hypertrophy and scarring in mutation positive hypertrophic
      cardiomyopathy.

PMID- 20051425
TI  - Primary percutaneous coronary intervention by magnetic navigation compared with
      conventional wire technique.
AB  - Aims Comparison of magnetic guidewire navigation in percutaneous coronary
      intervention (MPCI) vs. conventional percutaneous coronary intervention (CPCI)
      for the treatment of acute myocardial infarction. Methods and results We compared
      65 sequential patients (mean age 61 +/- 15 years) undergoing primary MPCI with
      those of 405 patients undergoing CPCI (mean age 61 +/- 13 years). The major
      endpoint was contrast media use. Technical success and procedural outcomes were
      evaluated. Clinical demographics and angiographic characteristics of the two
      groups were similar, except for fewer patients with previous coronary artery
      bypass grafting (CABG) and hypertension in the CPCI group and fewer patients with
      diabetes in the MPCI group. The technical success rate was high in both the MPCI
      and CPCI groups (95.4 vs. 98%). There was significantly less contrast media usage
      in the MPCI compared with the CPCI group, median reduction of contrast media of
      30 mL with an OR = 0.41 (0.21-0.81). Fluoroscopy times were significantly reduced
      for MPCI compared with CPCI, median reduction of 7.2 min with an OR = 0.42 (0.20
      0.79). Conclusion This comparison indicates the feasibility and non-inferiority
      of magnetic navigation in performing primary PCI and suggests the possibility of
      reductions in contrast media use and fluoroscopy time compared with CPCI.

PMID- 20051427
TI  - Health scares: Professional priorities.
AB  - Currently, many health scholars are concerned about health scares. But what do
      they mean by the term 'health scare' - are health scares an identifiable
      phenomenon and how do we currently understand their causation and consequences?
      By collecting and analysing published articles about events considered to be
      health scares, this article maps the current views of scholars on their
      characteristics and causes. Results show that health scares are generally
      understood as events characterized by fears of catastrophic consequences but
      little actual mortality. However, the social and economic impacts of these events
      have often been severe. This survey shows that health scares can be usefully
      sorted into six categories, each with identifiable internal dynamics, suggesting
      different communications strategies to achieve resolution in each category. Using
      the social amplification of risk framework, the conditions under which risk
      signals were amplified were traced in general terms among major stakeholders.
      Simple causes for health scare events could not be identified, though some
      triggers did emerge. Importantly, public ignorance of real risk, media
      scaremongering and political inaction could be dismissed as primary explanations,
      though they were sometimes factors in scare events. Implications for risk
      communication and for future research on risk and public health are discussed.

PMID- 20051426
TI  - Heart-specific overexpression of CUGBP1 reproduces functional and molecular
      abnormalities of myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is caused by a CTG expansion within the 3'
      untranslated region of the DMPK gene. The predominant mechanism of pathogenesis
      is a toxic gain of function of CUG repeat containing RNA transcribed from the
      expanded allele. The molecular mechanisms by which the RNA containing expanded
      repeats produce pathogenic effects include: sequestration of muscleblind-like 1
      (MBNL1) protein and up-regulation of CUG binding protein 1 (CUGBP1). MBNL1 and
      CUGBP1 are RNA binding proteins that regulate alternative splicing transitions
      during development. Altered functions of these proteins in DM1 lead to
      misregulated splicing of their target genes, resulting in several features of the
      disease. The role of MBNL1 depletion in DM1 is well established through a mouse
      knock-out model that reproduces many disease features. Here we directly test the
      hypothesis that CUGBP1 up-regulation also contributes to manifestations of DM1.
      Using tetracycline-inducible CUGBP1 and heart-specific reverse tetracycline trans
      activator transgenes, we expressed human CUGBP1 in adult mouse heart. Our results
      demonstrate that up-regulation of CUGBP1 is sufficient to reproduce molecular,
      histopathological and functional changes observed in a previously described DM1
      mouse model that expresses expanded CUG RNA repeats as well as in individuals
      with DM1. These results strongly support a role for CUGBP1 up-regulation in DM1
      pathogenesis.

PMID- 20051428
TI  - Quitting is not an option: An analysis of online diet talk between celiac disease
      patients.
AB  - This is an empirical study of the way in which celiac disease patients manage the
      risk of gluten intake in their everyday life.The article examines naturally
      occurring conversational data in order to study how patients cope interactionally
      with constantly being at risk in their day-to-day living. They reject quitting
      the diet as a valid option, and instead construct a 'diet world' in which dietary
      transgression is presented as an integrated part of everyday life. In this way,
      patients can manage occasional diet lapses without putting the validity of the
      diet itself at stake. By examining how the gluten-free diet is treated in
      interaction, we find out more about the pre-existing everyday strategies that
      have to be taken into account when new therapies are being introduced.

PMID- 20051429
TI  - A 'healthy baby': The double imperative of preimplantation genetic diagnosis.
AB  - This article reports from a study exploring the social processes, meanings and
      institutions that frame and produce 'ethical problems' and clinical dilemmas for
      practitioners, scientists and others working in the specialty of preimplantation
      genetic diagnosis (PGD). A major topic in the data was that, in contrast to IVF,
      the aim of PGD is to transfer to the woman's womb only those embryos likely to be
      unaffected by serious genetic disorders; that is, to produce 'healthy babies'.
      Staff described the complex processes through which embryos in each treatment
      cycle must meet a double imperative: they must be judged viable by embryologists
      and 'unaffected' by geneticists. In this article, we focus on some of the
      ethical, social and occupational issues for staff ensuing from PGD's double
      imperative.

PMID- 20051430
TI  - 'Do your best for me': The difficulties of finding a clinically effective
      endpoint in smoking cessation consultations in primary care.
AB  - In recent years in the UK there has been a shift towards doctors practising
      preventative medicine. Research suggests, however, that doctors are more
      comfortable in their traditional role, and may be reluctant to engage in
      discussion of lifestyle issues with patients. In this article, we use data from
      GPs' consultations about smoking, recorded prior to the availability of Nicotine
      Replacement Therapy on NHS prescription, to demonstrate how they attempt to
      negotiate behaviour change. Using a discursive analytic approach, and drawing
      particularly on some of the conversation analytic literature on advice giving, we
      suggest that there are two kinds of difficulties for doctors to overcome: an
      ambiguity about the interactional endpoint of a discussion about smoking; and the
      inability to offer 'expert' medical help. As a result, doctors struggle with
      following through their advice to stop in terms of talking about how to do it. We
      suggest that the efficacy of nicotine addiction treatments may be due not only to
      their clinical effects, but also because their prescription legitimizes the
      difficulty in stopping reported by most smokers as an appropriate problem for
      medical treatment. We discuss the implications of these findings for the
      management of smoking and other lifestyle issues within primary care
      consultations.

PMID- 20051431
TI  - The impact of early stroke on identity: A discourse analytic study.
AB  - This article examines the ways in which sufferers talk about early stroke and the
      effects this chronic condition has on identity. Traditional research into chronic
      illness has largely used medical, psychiatric or cognitive models. We adopt a
      social constructionist perspective and use a discourse analytic methodology to
      study data collected via focus group interaction. Analysis of the data collected
      shows that participants displayed sensitivity about having acquired a potentially
      'damaged' sense of self by mitigating negative features of their experiences.
      Participants also attended to the issue of whether their accounts were persuasive
      or believable. Some carers were present in these discussions. As a consequence,
      participants who had suffered a stroke displayed sensitivity to the way that
      carers might respond to mitigation of the negative aspects of stroke.

PMID- 20051433
TI  - Studies sit at various points along a continuum from the initial testing of
      interventions to more formally constructed trials of effectiveness.

PMID- 20051432
TI  - From consumerism to active dependence: Patterns of medicines use and treatment
      decisions among patients with atopic dermatitis.
AB  - In this article, findings from in-depth interviews with 12 people diagnosed with
      atopic dermatitis (AD) are described. The findings describe the range of
      strategies used to manage atopic dermatitis, including use of conventional
      medicines. A strong theme identified in informants' accounts centred on concerns
      about the risks of illness and long-term use of conventional medicines, which
      acted as a strong incentive for patients to seek alternatives to conventional
      treatments. However, despite their significant efforts to do so, patients were
      eventually forced to return to and rely on conventional medicines because of
      their efficacy in alleviating and treating symptoms. These findings are discussed
      in relation to the sociological literature on consumerism, risk and reflexivity
      in health. We argue that our findings exemplify how living with and managing a
      chronic illness may not be straightforward and the choices of treatment at hand
      may be limited. Consequently, this may limit the potential opportunities accruing
      from adopting a reflexive or consumerist approach to managing illness.

PMID- 20051434
TI  - Test of time: Dibs: in search of self.
AB  - The book, Dibs: In Search of Self, by Virginia Axline was first published in
      1964. It is a session-by-session description of a relatively short therapeutic
      intervention with a troubled and imaginative child named Dibs. The book shows how
      the therapist and child work together and how the child changes. This article
      revisits the book from the perspective of the psychoanalytic thinking of a child
      psychotherapist. It describes the author's thoughts in re-reading the book,
      including the clinical content of the book and the motive for the writing of the
      book, and attempts to explore the contemporary relevance of this account in the
      context of the author's current working experience within the NHS.

PMID- 20051435
TI  - Janus kinase 2: an epigenetic 'writer' that activates leukemogenic genes.
AB  - Activation of Janus kinase 2 (JAK2) plays a critical role in normal hematopoiesis
      and leukemogenesis. Dawson et al. (2009; JAK2 phosphorylates histone H3Y41 and
      excludes HP1alpha from chromatin. Nature 461, 819-822) report that JAK2 performs
      this function by displacing the heterochromatin protein HP1alpha from chromatin
      through phosphorylation of histone H3.

PMID- 20051436
TI  - In this issue of Occupational Medicine.

PMID- 20051437
TI  - From dust and ashes: the 1950s.

PMID- 20051438
TI  - The SOM journal in the 1950s.

PMID- 20051439
TI  - GMC guidance on confidentiality: is it ethical?

PMID- 20051440
TI  - William Hogarth.

PMID- 20051441
TI  - Shift work: coping with the biological clock.
AB  - The internal circadian clock adapts slowly, if at all, to rapid transitions
      between different shift schedules. This leads to misalignment (desynchrony) of
      rhythmic physiological systems, such as sleep, alertness, performance, metabolism
      and the hormones melatonin and cortisol, with the imposed work-rest schedule.
      Consequences include sleep deprivation and poor performance. Clock gene variants
      may influence tolerance of sleep deprivation. Shift work is associated with an
      increased risk of major disease (heart disease and cancer) and this may also, at
      least in part, be attributed to frequent circadian desynchrony. Abnormal
      metabolism has been invoked as a contributory factor to the increased risk of
      heart disease. There is recent evidence for an increased risk of certain cancers,
      with hypothesized causal roles of light at night, melatonin suppression and
      circadian desynchrony. Various strategies exist for coping with circadian
      desynchrony and for hastening circadian realignment (if desired). The most
      important factor in manipulating the circadian system is exposure to and/or
      avoidance of bright light at specific times of the 'biological night'.

PMID- 20051442
TI  - Directly read.

PMID- 20051443
TI  - Mini-monitor.

PMID- 20051444
TI  - The strange case of Irving Selikoff.

PMID- 20051445
TI  - (Lack of) Impacts on work absence and performance.

PMID- 20051446
TI  - Phosphatidylinositol 3-kinase isoforms as targets in respiratory disease.
AB  - Respiratory diseases such as chronic obstructive pulmonary disease [COPD], severe
      asthma, cystic fibrosis [CF] and idiopathic pulmonary fibrosis [IPF] are
      inadequately controlled by current therapies. The underlying molecular mechanisms
      and pathogenesis of these diseases remain unclear, making identification and
      validation of potential new therapeutic targets difficult. However, recent
      studies have identified the central signalling mediator PI3K as playing an
      integral role in the immune system including initiation and maintenance of
      inflammatory responses. Specifically, the relatively leukocyte-specific PI3Kgamma
      and PI3Kdelta isoforms are central to leukocyte function and can be targeted
      pharmacologically. Early to man studies using selective PI3K isoform inhibitors
      are required to determine whether they have a future in treating respiratory
      disease, particularly in controlling both innate and adaptive inflammatory
      responses as well as restoring glucocorticoid function and reducing
      tumorigenesis.

PMID- 20051447
TI  - Quality of life in patients with chronic cough.
AB  - Chronic cough is a relatively common symptom for which effective, acceptable
      treatments are lacking. Many patients suffer frequent coughing over several years
      without resolution and this has significant physical, social and psychological
      consequences. The recent development of cough-specific quality-of-life tools now
      allows quantification of the burden of coughing both in patients specifically
      presenting with chronic cough and also in common respiratory conditions.

PMID- 20051448
TI  - Attenuation of isoproterenol-induced cardiac fibrosis in transgenic rats
      harboring an angiotensin-(1-7)-producing fusion protein in the heart.
AB  - OBJECTIVE: It has been shown that Ang-(1-7) has cardioprotective actions. To
      directly investigate the effects of Ang-(1-7) specifically in the heart, we
      generated and characterized transgenic (TG) rats which express an Ang-(1-7)
      producing fusion protein driven by the alpha-MHC promoter. METHODS AND RESULTS:
      After microinjection of the transgene into fertilized rat zygotes, we obtained
      four different transgenic lines. Homozygous animals were analyzed with regard to
      the expression profile of the transgene by ribonuclease protection assay.
      Transgene expression was detected mainly in the heart with weak or no expression
      in other organs. Heterozygous TG(hA-1-7)L7301 rats presented a significant
      increase in cardiac Ang-(1-7) concentration compared with control rats (17.1+/
      2.1 versus 3.9+/-1.4 pg/mg protein in SD rats). Radiotelemetry analysis revealed
      that TG rats presented no significant changes in blood pressure and heart rate
      compared with normal rats. Overexpression of Ang-(1-7) in the heart produced
      slight improvement in resting cardiac function (+ dT/dt: 81530+/-1305.0 versus
      77470+/-345.5 g/s bpm in SD rats, p < 0.05), which was in keeping with the
      enhanced [Ca(2+)] handling observed in cardiomyocytes of TG rats. TG(hA-1-7)L7301
      rats also showed a greater capacity to withstand stress since TG rats showed a
      less pronounced deposition of collagen type III and fibronectin induced by
      isoproterenol treatment in the subendocardial area than in corresponding
      controls. In addition, hearts from TG rats showed reduced incidence and duration
      of reperfusion arrhythmias in comparison with SD rats. CONCLUSION: These results
      indicate that Ang-(1-7) has blood pressure-independent, antifibrotic effects,
      acting directly in the heart.

PMID- 20051449
TI  - Management of a pulsatile mass coming through the sternum. Pseudoaneurysm of
      ascending aorta 35 years after repair of tetralogy of Fallot.
AB  - We describe a case of an ascending aortic pseudoaneurysm during long-term follow
      up after repair of tetralogy of Fallot (TOF). The patient had a complex cardiac
      surgical history with multiple operations for the correction of TOF. The aneurysm
      was located at the presumed site of previous aortic cannulation. It was initially
      treated percutaneously with an Amplatzer septal occluder device, with limited
      early success. After 12 months it was found to have migrated into the sac and
      open surgical repair was undertaken successfully.

PMID- 20051450
TI  - Effect of hydrogen sulfide on myocardial protection in the setting of
      cardioplegia and cardiopulmonary bypass.
AB  - We investigated the impact of hydrogen sulfide (H(2)S) on myocardium in the
      setting of cold crystalloid cardioplegia and cardiopulmonary bypass (CP/CPB).
      Eighteen male Yorkshire pigs underwent 1 h CP/CPB followed by 2 h of reperfusion.
      Pigs received either: placebo (control, n=9), or H(2)S (as NaHS) as a
      bolus/infusion (bolus/infusion, n=6), or as an infusion (infusion, n=6). The
      expression pattern of various myocardial effector pathways was investigated.
      Coronary microvascular relaxation to endothelium-dependent and -independent
      agonists was assessed. No differences in cardiac function were observed among
      groups. Endothelium-dependent microvascular relaxation to adenosine diphosphate
      was improved in the H(2)S bolus/infusion group only (P<0.05). The expression of
      hemeoxygenase-1, phospho-heat shock proteins27 and phospho-p44/42 MAPK
      extracellular signal-regulated kinase were higher in H(2)S-treated groups
      (P<0.05). Phospho-endothelial nitric oxide synthase (P=0.08), phospho-B-cell
      lymphoma 2 (P=0.09), and phospho-Bad (P=0.06) all displayed a trend to be higher
      with H(2)S treatment. The expressions of apoptosis inducing factor and Bcl
      2/adenovirus E1B 19 kDa-interacting protein were lower in H(2)S treated groups
      (P<0.05). The microtubule-associated protein 1 light chain 3 ratio was lower in
      the infusion group vs. control animals (P<0.05). There was a trend for lower
      phospho-mammalian target of rapamycin expression in the infusion group (P=0.07),
      whereas phosphorylation of p70S6K1 was higher with H(2)S-treatment (P=0.09). This
      study demonstrates that H(2)S-treatment may offer biochemical myocardial
      protection via attenuation of caspase-independent apoptosis and autophagy in the
      setting of CP/CPB.

PMID- 20051451
TI  - Is the use of Steri-StripTM S for wound closure after coronary artery bypass
      grafting better than intracuticular suture?
AB  - Several methods have been used in wound closure after coronary artery bypass
      grafting (CABG). In this study, the safety and efficacy of one of these methods,
      Steri-Strip S is compared with the traditional intracuticular suture method.
      Eighty-one patients undergoing CABG were prospectively randomized into two groups
      according to the method of skin closure: Steri-Strip S group and traditional
      suture group. Comparison between the two methods was done with regards to the
      length of the wound and the time needed to close it. The median closure time with
      Steri-Strip S was 5.45+/-3.35 min vs. 7.53+/-3.41 min in the suture group. A pain
      score of >or=6 at the first postoperative day was found in 30% of the patients in
      the suture group vs. 14% of the patients in the Steri-Strip S group (P=0.07).
      Cosmetic evaluation showed a non-significant difference in the linear visual
      analogue score in favor of Steri-Strip S group compared to the intracuticular
      suture group (73.1 vs. 70.1) (P=0.07). Steri-Strip S is a fast, safe alternative
      for wound closure of the sternotomy incision and graft harvesting site. A larger
      study is needed to establish the potential beneficial effect of Steri-Strip S on
      wound infection prevention.

PMID- 20051452
TI  - Despite modern off-pump coronary artery bypass grafting women fare worse than
      men.
AB  - Female gender is an established risk factor for worse outcomes after cardiac
      surgery. Avoiding cardiopulmonary bypass (CPB) for coronary bypass grafting has
      an unknown effect on gender differences. Herein, we evaluate if gender has an
      impact on outcomes after modern off-pump coronary artery bypass grafting (OPCAB).
      From 2002 to 2007, we analyzed 983 patients (male: n=807/female: n=176) who
      underwent OPCAB with symptomatic multi-vessel disease at our institution. The
      link between gender and outcome was assessed by multivariate analysis and
      logistic regression. A composite endpoint was constructed from: 30-day-mortality,
      renal failure, prolonged intensive care unit (ICU) stay, neurological
      complications, use of intra-aortic balloon pump (IABP) and conversion to CPB.
      Mortality was 3.2% in women vs.1.8% in men (P=0.15) and the EuroSCORE was
      significantly correlated to gender (6.8 vs. 5.2; P<0.001), even after correction
      (P=0.036). Significant more occurrence of the composite endpoint was noted in
      women (39.8% vs. 29.0%; P=0.007) whereas for men the risk was much lower [odds
      ratio (OR) 0.65; 95% confidence interval (CI) 0.46-0.92; P=0.015]. For both
      genders the logistic regression revealed a risk increase of 15% per one-point
      increase of EuroSCORE (corrected) (OR 1.15; 95% CI: 1.10-1.19; P<0.0001). Women
      had more frequently a prolonged stay at ICU (P=0.006) and had a higher stroke
      rate (2.3% vs. 1.2%; P=0.29). Complete revascularization was achieved similarly
      (95% vs. 94%; P=0.93). OPCAB offers low mortality and excellent clinical outcome.
      Women are more likely to experience postoperative complications. Even if
      partially neutralized by avoiding CPB, gender differences remain present with
      modern OPCAB strategies.

PMID- 20051453
TI  - The effect of 2,5-hexanedione on permeability of blood-nerve barrier in rats.
AB  - To explore the effect of 2,5-hexanedione on permeability of blood-nerve barrier,
      adult Wistar rats were administered with 400 mg x kg(-1) x d(- 1) 2,5-hexanedione
      to establish animal model of 2,5-hexnedione neuropathy. Evans blue was injected
      through left femoral vein of the rats after the model had been established. The
      distribution of fluorescence in sciatic-tibial nerve was observed and assessed.
      For the transverse sections of sciatic-tibial nerves, the average fluorescence
      intensity of proximal section was stronger (p < .01) than those of intermediate
      and distal sections and the average fluorescence intensity of intermediate
      section was stronger (p < .01) than that of distal section in the intoxicated
      group. In the control, the weak fluorescence was shown, and average fluorescence
      intensity of distal section was stronger (p < .05) than that of proximal section.
      The average fluorescence intensity of proximal, intermediate and distal sections
      in the intoxicated group was stronger (p < .01) than those of the corresponding
      sections in the control. For the longitudinal sections of sciatic-tibial nerves,
      fluorescence was observed in both proximal and distal sections in the intoxicated
      group. The fluorescence intensity of distal section in the control was weak and
      almost no fluorescence was shown in the proximal section. The permeability of
      blood-nerve barrier could be increased by 2,5-hexanedione.

PMID- 20051454
TI  - Lethal complications after poisoning with chloroform--case report and literature
      review.
AB  - Chloroform is a potent central nervous system and respiratory depressant. The
      toxicities associated with chloroform frequently occur after inhalation.
      Hepatotoxicity is secondary to production of a toxic metabolite, with a peak
      elevation of liver enzymes 72 hours after exposure. Acute liver failure after
      chloroform inhalation is rarely described, this syndrome being produced mainly by
      viral hepatitis, idiosyncratic drug-induced liver injury, and acetaminophen
      ingestion. This report describes the case of a 46-year-old woman who presented to
      emergency department with coma, signs of respiratory failure, and solvent odor of
      her breath after chloroform inhalation and binge drinking. In evolution appeared
      lethal acute liver failure and rhabdomyolysis, despite maximum supportive care.
      Necroptic examination revealed microvesicular steatosis and tubular renal
      necrosis, specific for chloroform toxicity. This case illustrates the dramatic
      impact on liver of two well-recognized hepatotoxins. Mechanisms of chloroform and
      alcohol-induced liver toxicity are reviewed.

PMID- 20051455
TI  - An evaluation of the genotoxic and cytotoxic effects of the anti-obesity drugs
      sibutramine and fenproporex.
AB  - Anti-obesity medications deserve special considerations at the present time due
      to an increasing number of overweight and obese people who require these
      therapeutic alternatives. Obesity is positively associated with several chronic
      illnesses, including cancer. In this work, we evaluated the possible genotoxic
      and/or cytotoxic actions of two drugs, sibutramine and fenproporex, in the doses
      of 10, 20 and 40 mg/kg body weight (bw), administered intraperitoneally in male
      Swiss mice. The genotoxic effect was analyzed by comet assay and micronucleus
      test. We found that both drugs increased the frequency of genotoxic damage in
      Swiss mice, but did not present cytotoxic activities towards the polychromatic
      erythrocytes of the bone marrow of these animals.

PMID- 20051456
TI  - Anti-ulcer role of herbomineral Siddha drug - Thamira parpam on experimentally
      induced gastric mucosal damage in rats.
AB  - Anti-ulcerogenic activity of Thamira parpam (TP) was investigated in two ulcer
      models (aspirin + pylorus ligation and HCl-ethanol). Aspirin-pylorus ligation
      (Asp 200 mg/kg-7 days + PL-4 hours) and HCl-ethanol (150 mM HCl in 70% ethanol)
      induction in rat resulted in elevation of thiobarbituric acid reactive substances
      (TBARS) and depletion of antioxidants (superoxide dismutase [SOD], glutathione
      [GSH], glutathione peroxidase [GPx]) with high ulcer scores (p < .01). In Asp +
      PL model, TP treatment showed mild inhibition on ulcer scores, changes in pH,
      gastric volume, total and free acidity, and elevation of TBARS and depletion of
      antioxidants. Compared to the ulcer-untreated rats (HCl-ethanol), the
      herbomineral drug TP treatment (0.5, 1, 2 mg/kg, per oral [p.o.]) attenuated the
      elevation of TBARS, decrease of antioxidants and nitrite (p < .05).
      Histopathological examinations were correlated with the antioxidant profile. In
      conclusion, the prophylactic cytoprotective nature of the herbomineral drug in
      experimentally induced ulcers could be mediated by its free radical quenching
      property.

PMID- 20051457
TI  - Evaluation of curcumin and cisplatin-induced DNA damage in PC12 cells by the
      alkaline comet assay.
AB  - A very appropriate method for antigenotoxicity evaluation of antioxidants is the
      comet assay, since this analytical method detects initial DNA lesions that are
      still subject to repair; in other words, lesions that are very associated to
      damages resulting from the generation and subsequent action of reactive species.
      However, a solid evaluation should be developed in order to avoid inexact
      interpretations. In our study, besides the association of curcumin with
      cisplatin, curcumin and cisplatin agents were also tested separately. Classical
      genotoxic compounds, when tested by the comet assay, present an increase in the
      nucleoid tail; however, the cisplatin treatment has resulted in a decrease of DNA
      migration. This was an expected effect, as the cross-links between cisplatin and
      DNA decrease the DNA electrophoretic mobility. A similar effect was observed with
      the curcumin treatment, which decreased the nucleoid tail. Such effect was not
      expected and reinforced the necessity of including in the study, separate
      treatment groups with potentially antigenotoxic substances. The comet assay
      results have been analyzed using specific software for image analysis, as well as
      the classical visual analysis, and we have observed that the effect of decrease
      in DNA electrophoretic mobility was more easily observed when the data were
      analyzed by the software.

PMID- 20051458
TI  - Effects of Cecropia pachystachya and Larrea divaricata aqueous extracts in mice.
AB  - Our studies were performed to investigate the effects of the aqueous extracts of
      Cecropia pachystachya and Larrea divaricata. These plants are used in folkloric
      medicine in infusion and were administered orally (0.76 g/kg) to male Albino
      Swiss mice for 16 days, on drink intake, organ weight/body weight (OW/BW x 100)
      ratio, histology, broqueoalveolar fluid (BALF) and elevated plus-maze (EPM).
      Feeding as well as body weight were unaffected by the consumption of these
      extracts. There were no signs of toxicity in BALF, morbidity or mortality during
      the study. C. pachystachya caused an increase in relative kidney OW/BW (p <or=
      .05 vs control). The macroscopic and microscopic morphologic analyses of the
      organs were not altered by administration of these plants. A non-anxiolytic-like
      activity of an aqueous extract prepared from the leaves of C. pachystachya and L.
      divaricata in EPM was observed. We conclude that the crude aqueous extracts of
      leaves tested on mice orally did not produce signs of toxicity or behavioral
      changes in routine histological and clinical evaluation. However, knowledge of
      the biological activity of many herbal medicine used in Latin American is still
      deficient and more studies will be needed to elucidate the possible toxic
      effects.

PMID- 20051459
TI  - Evidence-based medicine or instinct-based medicine?

PMID- 20051460
TI  - Commentary on: Calculating mixed venous saturation during veno-venous ECMO.

PMID- 20051461
TI  - Commentary on: CardioWest total artificial heart.

PMID- 20051462
TI  - Secondhand smoke, vascular disease, and dementia incidence: findings from the
      cardiovascular health cognition study.
AB  - Recent studies have found that smoking is associated with an increased risk of
      dementia, but the effects of secondhand smoke (SHS) on dementia risk are not
      known to have previously been studied. The authors used Cox proportional hazards
      marginal structural models to examine the association between self-reported
      lifetime household SHS exposure and risk of incident dementia over 6 years among
      970 US participants in the Cardiovascular Health Cognition Study (performed from
      1991 to 1999) who were never smokers and were free of clinical cardiovascular
      disease (CVD), dementia, and mild cognitive impairment at baseline. In addition,
      because prior studies have found that SHS is associated with increased risk of
      CVD and that CVD is associated with increased risk of dementia, the authors
      tested for interactions between SHS and measures of clinical and subclinical CVD
      on dementia risk. Moderate (16-25 years) and high (>25 years) SHS exposure levels
      were not independently associated with dementia risk; however, subjects with >25
      years of SHS exposure and >25% carotid artery stenosis had a 3-fold increase
      (hazard ratio = 3.00, 95% confidence interval: 1.03, 9.72) in dementia risk
      compared with subjects with no/low (0-15 years) SHS exposure and < or =25%
      carotid artery stenosis. High lifetime SHS exposure may increase the risk of
      dementia in elderly with undiagnosed CVD.

PMID- 20051463
TI  - Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating
      EDC3.
AB  - Insulin plays an essential role in metabolic homeostasis in mammals, and many of
      the underlying biochemical pathways are regulated via the canonical
      phosphatidylinositol 3-kinase/AKT pathway. To identify novel metabolic actions of
      insulin, we conducted a quantitative proteomics analysis of insulin-regulated 14
      3-3-binding proteins in muscle cells. These studies revealed a novel role for
      insulin in the post-transcriptional regulation of mRNA expression. EDC3, a
      component of the mRNA decay and translation repression pathway associated with
      mRNA processing bodies, was shown to be phosphorylated by AKT downstream of
      insulin signaling. The major insulin-regulated site was mapped to Ser-161, and
      phosphorylation at this site led to increased 14-3-3 binding. Functional studies
      indicated that induction of 14-3-3 binding to EDC3 causes morphological changes
      in processing body structures, inhibition of microRNA-mediated mRNA post
      transcriptional regulation, and alterations in the protein- protein interactions
      of EDC3. These data highlight an important new arm of the insulin signaling
      cascade in the regulation of mRNA utilization.

PMID- 20051464
TI  - Sex-specific correlates of walking speed in a wide age-ranged population.
AB  - The goals of this cross-sectional study were to explore correlates of walking
      speed in a large wide age-ranged population and to identify factors affecting
      lower walking speed at older ages. Participants were 3,872 community-dwelling
      adults in the first follow-up of the SardiNIA study who completed a 4-m walking
      test. Sex-specific correlates of walking speed included marital status, height,
      waist circumference, pulse wave velocity, comorbidity, subjective health,
      strength, and personality. Effect modifiers of the age-walking speed association
      included extraversion (<55 years, p = .019) and education (<55 years, p = .021; >
      or =55 years, p = .012) in women, and openness (<55 years, p = .005), waist
      circumference (<55 years, p = .010), and subjective health (<55 years, p = .014)
      in men. The strong impact of personality suggests that certain personality traits
      may be associated with behaviors that affect physical performance and condition
      the reduced mobility mostly at younger ages. If these patterns are confirmed in
      longitudinal studies, personality may be an important target for prevention.

PMID- 20051465
TI  - Treatment of childhood obesity by retraining eating behaviour: randomised
      controlled trial.
AB  - OBJECTIVE: To determine whether modifying eating behaviour with use of a feedback
      device facilitates weight loss in obese adolescents. DESIGN: Randomised
      controlled trial with 12 month intervention. SETTING: Hospital based obesity
      clinic. PARTICIPANTS: 106 newly referred obese young people aged 9-17.
      INTERVENTIONS: A computerised device, Mandometer, providing real time feedback to
      participants during meals to slow down speed of eating and reduce total intake;
      standard lifestyle modification therapy. MAIN OUTCOME MEASURES: Change in body
      mass index (BMI) standard deviation score (SDS) over 12 months with assessment 18
      months after the start of the intervention. Secondary outcomes were body fat SDS,
      metabolic status, quality of life evaluation, change in portion size, and eating
      speed. RESULTS: Using the last available data on all participants (n=106), those
      in the Mandometer group had significantly lower mean BMI SDS at 12 months
      compared with standard care (baseline adjusted mean difference 0.24, 95%
      confidence interval 0.11 to 0.36). Similar results were obtained when analyses
      included only the 91 who attended per protocol (baseline adjusted mean difference
      0.27, 0.14 to 0.41; P<0.001), with the difference maintained at 18 months (0.27,
      0.11 to 0.43; P=0.001) (n=87). The mean meal size in the Mandometer group fell by
      45 g (7 to 84 g). Mean body fat SDS adjusted for baseline levels was
      significantly lower at 12 months (0.24, 0.10 to 0.39; P=0.001). Those in the
      Mandometer group also had greater improvement in concentration of high density
      lipoprotein cholesterol (P=0.043). CONCLUSIONS: Retraining eating behaviour with
      a feedback device is a useful adjunct to standard lifestyle modification in
      treating obesity among adolescents. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00407420.

PMID- 20051467
TI  - Treatment for hepatitis B.

PMID- 20051468
TI  - NICE and new: appraising innovation.

PMID- 20051470
TI  - Free holiday is offered to volunteers willing to test diarrhoea vaccine.

PMID- 20051472
TI  - The adhesion mediated by the P-selectin P-selectin glycoprotein ligand-1 (PSGL-1)
      couple is stronger for shorter PSGL-1 variants.
AB  - Interactions between P-sel and the PSGL-1 mediate the earliest adhesive events
      during an inflammatory response. Human PSGL-1 displays a high degree of genetic
      polymorphism that has been diversely associated with susceptibility to human
      diseases. In the central part of PSGL-1, a 10-aa motif is repeated 14, 15, or 16
      times. Moreover, two mutations, M62I and M274V, are often found giving the most
      common variant M62-M274 with 16 motifs (M16M) and its variants I62-M274 (I16M).
      Two other variants exist with 15 repeated motifs (M62-M274; M15M) and with 14
      motifs (M62-V274; M14V). We investigated the potential difference in the adhesive
      properties between these natural variants stably expressed in the HEK cell line
      by using the BFP technique. Their interactions with P-sel were found to be of
      catch bond-type, and the dissociation force was primarily dependent on the number
      of decameric motifs: the shorter the PSGL-1, the larger the bond strength.
      Finally, we found that the M62I mutation, which is close to the binding site to P
      sel, reduced the adhesiveness to P-sel effectively. Collectively, these data shed
      new light on the polymorphism of PSGL-1 and could help the research on its
      associations to human pathologies.

PMID- 20051473
TI  - Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL
      34), and CSF-1 receptor genes and gene products.
AB  - Macrophages are involved in many aspects of development, host defense, pathology,
      and homeostasis. Their normal differentiation, proliferation, and survival are
      controlled by CSF-1 via the activation of the CSF1R. A recently discovered
      cytokine, IL-34, was shown to bind the same receptor in humans. Chicken is a
      widely used model organism in developmental biology, but the factors that control
      avian myelopoiesis have not been identified previously. The CSF-1, IL-34, and
      CSF1R genes in chicken and zebra finch were identified from respective
      genomic/cDNA sequence resources. Comparative analysis of the avian CSF1R loci
      revealed likely orthologs of mammalian macrophage-specific promoters and
      enhancers, and the CSF1R gene is expressed in the developing chick embryo in a
      pattern consistent with macrophage-specific expression. Chicken CSF-1 and IL-34
      were expressed in HEK293 cells and shown to elicit macrophage growth from chicken
      BM cells in culture. Comparative sequence and co-evolution analysis across all
      vertebrates suggests that the two ligands interact with distinct regions of the
      CSF1R. These studies demonstrate that there are two separate ligands for a
      functional CSF1R across all vertebrates.

PMID- 20051474
TI  - Tigecycline resistance in Serratia marcescens associated with up-regulation of
      the SdeXY-HasF efflux system also active against ciprofloxacin and cefpirome.
AB  - OBJECTIVES: Efflux by RND-type transporters is known to confer resistance to
      tigecycline in several Enterobacteriaceae species and we examined the potential
      of this mechanism in Serratia marcescens using a clinical isolate and laboratory
      selected mutants. METHODS: Expression of RND-type efflux pump genes was analysed
      by real-time RT-PCR. Laboratory mutants were selected by exposure to either
      tigecycline or tetracycline in vitro. Efflux pump genes were inactivated by
      suicide plasmids containing the R6K gamma origin of replication. RESULTS: Higher
      tigecycline MICs correlated with elevated expression of the RND-type efflux pump
      genes sdeXY. Inactivation of sdeY or the outer membrane component gene hasF
      reduced MICs of tigecycline, tetracycline, ciprofloxacin and cefpirome to below
      those for strain NCTC 10211. A tetracycline-selected laboratory mutant also
      showed increases in sdeXY expression and tigecycline MIC. CONCLUSIONS: Up
      regulation of endogenous SdeXY-HasF-mediated efflux is associated with
      tigecycline resistance in S. marcescens along with MIC rises for tetracycline,
      ciprofloxacin and cefpirome. Inactivation of this efflux system reduced MICs of
      those compounds to below those for strain NCTC 10211.

PMID- 20051476
TI  - Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir
      treated patients and in in vitro infected cells.
AB  - OBJECTIVES: Our aim was to analyse the evolution of HIV-1 2-long terminal repeat
      (2-LTR) circular DNA in vitro and ex vivo in the presence of raltegravir.
      PATIENTS AND METHODS: Twenty-five patients starting a raltegravir-based regimen
      were included. Total HIV-1 DNA and 2-LTR DNA were quantified at baseline and in
      follow-up samples up to month 12. The effect of raltegravir on the formation of 2
      LTR circles was evaluated in HeLa P4 cells. The effect of raltegravir was also
      investigated by sequence analysis of the 2-LTR circle junctions. RESULTS: Among
      21 patients with undetectable 2-LTR DNA at baseline, 7 had detectable 2-LTR DNA
      during the follow-up. Three of four patients with detectable 2-LTR DNA at
      baseline had undetectable 2-LTR DNA during the follow-up (P = 0.27). The mean 2
      LTR level increased significantly (+0.07 log(10)/month, P = 0.02) in raltegravir
      treated patients, and a 2-LTR increase was also observed in raltegravir-treated
      HeLa P4 cells, with a peak at 3 days post-infection. 2-LTR DNA showed a high
      prevalence of deletions ex vivo (64.5%) and in vitro (50%) in the presence of
      raltegravir, which was not statistically different from the prevalence in
      untreated patients or cells. CONCLUSIONS: In antiretroviral-experienced patients
      receiving raltegravir, 2-LTR DNA increased while total HIV-1 DNA decreased over
      time. The frequent rearrangements found in 2-LTR sequences warrant further
      investigations to determine the dynamics of evolution of unintegrated HIV-1 DNA.

PMID- 20051477
TI  - Early skin toxicity as a predictive factor for tumor control in hepatocellular
      carcinoma patients treated with sorafenib.
AB  - INTRODUCTION: Sorafenib is an oral multikinase inhibitor that targets Raf kinase
      and receptor tyrosine kinases and has led to a longer median overall survival
      (OS) time and time to progression (TTP) in patients with advanced hepatocellular
      carcinoma (HCC). This study was conducted to assess the link between the
      antitumor efficacy of sorafenib and its early cutaneous side effects in advanced
      HCC patients. MATERIALS AND METHODS: All patients received 800 mg daily of
      sorafenib until progression or unacceptable toxicities. We retrospectively
      analyzed the incidence of rash and hand-foot skin reactions (HFSR) during the
      first month of treatment, comparing tumor control (partial response plus stable
      disease) and TTP. RESULTS: Sixty-five HCC patients treated with sorafenib were
      included in this analysis: 47 (73.3%) received sorafenib after failure of some
      local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty
      nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In
      patients who developed skin toxicity, the tumor control rate was 48.3%, versus
      19.4% in patients without cutaneous side effects. The median TTP was 8.1 months
      in the group of patients with skin toxicity versus 4.0 months in those without
      skin toxicity. This difference was also statistically significant on multivariate
      analysis. A borderline statistically significant difference was also observed in
      terms of OS in patients with early skin toxicity. CONCLUSIONS: Skin toxicity
      should be closely monitored in HCC patients treated with sorafenib in relation to
      its potential role as a surrogate marker of efficacy.

PMID- 20051475
TI  - Predictors of hepatitis B virus genotype and viraemia in HIV-infected patients
      with chronic hepatitis B in Europe.
AB  - BACKGROUND: Both natural history and treatment outcome of hepatitis B virus (HBV)
      infection are influenced by genotypes and viral load. Information about factors
      determining HBV genotype distribution and viraemia in HIV/HBV-co-infected
      patients is scarce. METHODS: All HIV-positive patients living in Europe and
      Argentina recruited in EuroSIDA (1994-2006) were tested for serum HBV surface
      antigen (HBsAg). Chronic carriers were further characterized virologically at one
      central laboratory. Variables influencing HBV genotype distribution and viraemia
      were assessed using logistic regression. RESULTS: From 16 505 HIV patients
      enrolled in EuroSIDA, 1179 (7.1%) were HBsAg positive, of whom 474 had specimens
      that allowed inclusion in the virological substudy. Overall 293 (62%) were
      treated with anti-HBV active antiretroviral drugs at the time of testing.
      Hepatitis delta virus superinfection was recognized in 14% and hepatitis C virus
      (HCV) antibodies in 27%. Serum HBV DNA was detectable in 315 (66.5%) and HBV
      genotyping gave results in 170 (35.9%) patients. HBV genotype distribution was as
      follows: A (72.9%), D (17.1%), G (1.8%), E (1.2%), F (1.2%) and C (0.6%); another
      5.9% were co-infected with multiple HBV genotypes. In the multivariate analysis,
      the best predictor of HBV genotype A infection was risk exposure other than
      intravenous drug use, whereas predictors for detectable HBV viraemia were lower
      CD4 counts and lack of HCV antibodies. CONCLUSION: A substantial proportion of
      HIV-positive patients with chronic hepatitis B show detectable HBV viraemia
      despite being treated with anti-HBV active antiretroviral drugs (mainly
      lamivudine). Low CD4 counts were associated with an independent higher risk of
      detectable HBV viraemia, which supports an earlier introduction of antiretroviral
      therapy, including anti-HBV drug(s) more potent than lamivudine.

PMID- 20051479
TI  - To mandatory nap or not to mandatory nap.

PMID- 20051478
TI  - Parathyroid carcinoma: current understanding and new insights into gene
      expression and intraoperative parathyroid hormone kinetics.
AB  - Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy.
      Due to the lack of definitive diagnostic markers and overlapping clinical
      features of benign primary hyperparathyroidism (PHPT), this disease is often
      misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion
      preoperatively and early intraoperative recognition with en bloc surgical
      resection are crucial for favorable outcome. Owing to the rarity of the disease,
      little is known about the molecular pathogenesis of parathyroid carcinoma. Here,
      we review the literature to present current understanding of the disease and
      provide new information on gene expression and use of intraoperative parathyroid
      hormone (PTH) monitoring in the surgical management of this rare malignancy.
      Specifically, using microarray transcriptome analysis of an unequivocal case of
      parathyroid carcinoma and a biopsy from the same patient's normal parathyroid
      gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes
      in parathyroid carcinoma. Further, using case records from four cases of
      unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of
      these patients to 475 patients with benign PHPT, and show that intraoperative PTH
      monitoring is accurate in predicting postoperative normocalcemia in initial en
      bloc operations for parathyroid carcinoma.

PMID- 20051480
TI  - Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin
      receptor phosphorylation.
AB  - Pasireotide (SOM230) is currently under clinical evaluation as a successor
      compound to octreotide for the treatment of acromegaly, Cushing's disease, and
      carcinoid tumors. Whereas octreotide acts primarily via the sst(2A) somatostatin
      receptor, pasireotide was designed to exhibit octreotide-like sst(2A) activity
      combined with enhanced binding to other somatostatin receptor subtypes. In the
      present study, we used phophosite-specific antibodies to examine agonist-induced
      phosphorylation of the rat sst(2A) receptor. We show that somatostatin and
      octreotide stimulate the complete phosphorylation of a cluster of four threonine
      residues within the cytoplasmic (353)TTETQRT(359) motif in a variety of cultured
      cell lines in vitro as well as in intact animals in vivo. This phosphorylation
      was mediated by G protein-coupled receptor kinases (GRK) 2 and 3 and followed by
      rapid cointernalization of the receptor and ss-arrestin into the same endocytic
      vesicles. In contrast, pasireotide failed to promote substantial phosphorylation
      and internalization of the rat sst(2A) receptor. In the presence of octreotide or
      SS-14, SOM230 showed partial agonist behavior, inhibiting phosphorylation, and
      internalization of sst(2A). Upon overexpression of GRK2 or GRK3, pasireotide
      stimulated selective phosphorylation of Thr356 and Thr359 but not of Thr353 or
      Thr354 within the (353)TTETQRT(359) motif. Pasireotide-mediated phosphorylation
      led to the formation of relatively unstable beta-arrestin-sst(2A) complexes that
      dissociated at or near the plasma membrane. Thus, octreotide and pasireotide are
      equally active in inducing classical G protein-dependent signaling via the
      sst(2A) somatostatin receptor. Yet, we find that they promote strikingly
      different patterns of sst(2A) receptor phosphorylation and, hence, stimulate
      functionally distinct pools of beta-arrestin.

PMID- 20051481
TI  - Kruppel-like factor 4 is widely expressed in the mouse male and female
      reproductive tract and responds as an immediate early gene to activation of the
      protein kinase A in TM4 Sertoli cells.
AB  - Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor critically
      involved in cell proliferation, differentiation, and carcinogenesis. Recently,
      KLF4 has also been used for the generation of induced pluripotent stem cells. In
      this study, we analyzed Klf4 expression in different mouse tissues using northern
      blot analysis and immunohistochemistry. Focusing on the male and female
      reproductive tract, we showed for the first time that KLF4 is expressed in the
      epithelia of the murine uterus and the vagina. In the male reproductive tract, we
      detected KLF4 in the epithelia of the epididymis, ductus deferens, coagulating
      gland, and the penis. As KLF4 is strongly inducible by FSH signaling in Sertoli
      cells and as this transcription factor is also involved in Sertoli cell
      development, we employed the mouse Sertoli cell line TM4 as a model system to
      investigate i) the induction kinetics of Klf4 upon activation of the cAMP/protein
      kinase A pathway by forskolin and ii) the effects of Klf4 induction on TM4 cell
      cycle progression. Interestingly, Klf4 mRNA and protein were rapidly but
      transiently induced, reaching peak levels after 90-120 min and declining to basal
      levels within 4 h. Compared with the inducible cAMP early repressor, an immediate
      early response gene, the induction kinetics of Klf4 is much faster. In
      conclusion, Klf4 is an immediate early gene in TM4 cells and its expression in
      several epithelia of the male and female reproductive tract suggests an important
      role of Klf4 in mouse reproductive functions.

PMID- 20051483
TI  - Cystic fibrosis transmembrane regulator inhibitors CFTR(inh)-172 and GlyH-101
      target mitochondrial functions, independently of chloride channel inhibition.
AB  - Two highly potent and selective cystic fibrosis (CF) transmembrane regulator
      (CFTR) inhibitors have been identified by high-throughput screening: the
      thiazolidinone CFTR(inh)-172 [3-[(3-trifluoromethyl)phenyl]-5-[(4
      carboxyphenyl)methylene]- 2-thioxo-4-thiazolidinone] and the glycine hydrazide
      GlyH-101 [N-(2-naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine
      hydrazide]. Inhibition of the CFTR chloride channel by these compounds has been
      suggested to be of pharmacological interest in the treatment of secretory
      diarrheas and polycystic kidney disease. In addition, functional inhibition of
      CFTR by CFTR(inh)-172 has been proposed to be sufficient to mimic the CF
      inflammatory profile. In the present study, we investigated the effects of the
      two compounds on reactive oxygen species (ROS) production and mitochondrial
      membrane potential in several cell lines: the CFTR-deficient human lung
      epithelial IB3-1 (expressing the heterozygous F508del/W1282X mutation), the
      isogenic CFTR-corrected C38, and HeLa and A549 as non-CFTR-expressing controls.
      Both inhibitors were able to induce a rapid increase in ROS levels and depolarize
      mitochondria in the four cell types, suggesting that these effects are
      independent of CFTR inhibition. In HeLa cells, these events were associated with
      a decrease in the rate of oxygen consumption, with GlyH-101 demonstrating a
      higher potency than CFTR(inh)-172. The impact of CFTR inhibitors on inflammatory
      parameters was also tested in HeLa cells. CFTR(inh)-172, but not GlyH-101,
      induced nuclear translocation of nuclear factor-kappaB (NF-kappaB). CFTR(inh)-172
      slightly decreased interleukin-8 secretion, whereas GlyH-101 induced a slight
      increase. These results support the conclusion that CFTR inhibitors may exert
      nonspecific effects regarding ROS production, mitochondrial failure, and
      activation of the NF-kappaB signaling pathway, independently of CFTR inhibition.

PMID- 20051482
TI  - Persistent induction of cytochrome P4501A1 in human hepatoma cells by 3
      methylcholanthrene: evidence for sustained transcriptional activation of the
      CYP1A1 promoter.
AB  - Cytochrome P450 (P450)1A1 plays a critical role in the metabolic activation and
      detoxification of polycyclic aromatic hydrocarbons (PAHs), many of which are
      potent human carcinogens. In this investigation, we tested the hypothesis that MC
      elicits persistent induction of CYP1A1 expression in human hepatoma cells (HepG2)
      and that this phenomenon is mediated by sustained transcriptional activation of
      the CYP1A1 promoter. Treatment of HepG2 cells with MC resulted in marked
      induction (8-20-fold) of ethoxyresorufin O-de-ethylase activities, CYP1A1
      apoprotein contents, and mRNA levels, which persisted for up to 96 h. MC also
      caused sustained transcriptional activation of the human CYP1A1 promoter for up
      to 96 h, as inferred from transient transfection experiments. Experiments with
      deletion constructs indicated that Ah response elements located at -886, -974,
      and -1047, but not -491, nucleotides from the start site, contributed to the
      sustained transcriptional activation of the CYP1A1 promoter. Electrophoretic
      mobility-shift and chromatin immunoprecipitation assays suggested that prolonged
      CYP1A1 induction was mediated by Ah receptor (AHR)-independent mechanisms.
      Experiments with [3H]MC and liquid chromatography-tandem mass spectrometry
      demonstrated rapid elimination of MC and its metabolites from the cells by 12 to
      24 h, suggesting that these compounds did not elicit sustained CYP1A1 induction
      via the classical AHR-mediated pathway. In conclusion, the results of this study
      support the hypothesis that MC causes persistent induction of CYP1A1 in human
      hepatoma cells by mechanisms entailing sustained transcriptional activation of
      the CYP1A1 promoter via AHR-independent mechanisms. These observations have
      important implications for human carcinogenesis mediated by PAHs.

PMID- 20051484
TI  - Differential effect of L-cysteine in isolated whole-bladder preparations from
      neonatal and adult rats.
AB  - The present study was undertaken to compare the effects of the thiol reagents L
      cysteine and (diazene dicarboxylic acid bis 5N,N-dimethylamide) diamide on
      contractile activity of neonatal and adult rat bladders. In vitro whole-bladder
      preparations from Wistar rats were used to study the modulation of spontaneous
      bladder contractions by thiol reagents. After blocking cholinergic and adrenergic
      transmission with atropine and guanethidine, L-cysteine facilitated spontaneous
      bladder contractions in neonatal rat bladders. The effect of L-cysteine was
      suppressed by diamide. Diamide alone did not change basal activity of the
      neonatal rat bladder. The facilitatory effects of L-cysteine were reduced by the
      L-type Ca2+ channel-blocking agent nifedipine and the calcium-activated K+
      channel opener NS1619 [1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5
      (trifluoromethyl)-2H-benzimidazol-2-one]. ATP or suramin, a purinergic receptor
      antagonist, significantly inhibited the effect of L-cysteine in neonatal
      bladders, whereas the nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine
      was ineffective. L-cysteine did not elicit any detectable effects in the adult
      rat bladder; whereas diamide caused a large-amplitude sustained tonic
      contraction. The contraction induced by diamide in adult bladder did not occur
      when the preparation was pretreated with L-cysteine. Also, L-Cysteine
      administered during the diamide-evoked contraction completely inhibited the
      contraction to diamide. In conclusion, our results suggest that L-cysteine has
      markedly different effects in isolated whole-bladder preparations from neonatal
      and adult rats. Thus thiol-sensitive mechanisms may modulate contractility by
      regulation of Ca2+ and K+ channels and/or purinergic transmission in the neonatal
      bladder. The effects of L-cysteine and diamide were reversed in adult bladders,
      indicating that the regulation of bladder contractility by thiols is markedly
      altered during postnatal development.

PMID- 20051485
TI  - Effects of estradiol on the thermoneutral zone and core temperature in
      ovariectomized rats.
AB  - Hot flushes represent a disorder of central thermoregulation characterized by the
      episodic activation of heat loss mechanisms. Although flushes are associated with
      estrogen withdrawal, there is little understanding of the effects of estrogen on
      thermoregulation in any species. It has been proposed that hormone withdrawal
      increases the sensitivity of hypothalamic neural pathways that control heat
      dissipation effectors. If so, we predicted that ovariectomized rats without
      estradiol treatment would activate tail skin vasodilatation (a major heat loss
      effector) at lower ambient temperatures and thereby lower the thermoneutral zone.
      The thermoneutral zone, defined as the range of ambient temperatures in which
      thermoregulation is achieved only by sensible (dry) heat loss, was evaluated
      based on properties of skin vasomotion. Core and tail skin temperatures were
      recorded in ovariectomized rats (with and without estradiol-17beta) exposed to
      ambient temperatures from 13 to 34 C in an environmental chamber. Rats without
      estradiol exhibited increased skin vasodilatation and a shift in the
      thermoneutral zone to lower ambient temperatures. Moreover, the ambient
      temperature threshold for skin vasodilatation was significantly lower in rats
      without estradiol treatment. At most ambient temperatures, average core
      temperature was unaffected by estradiol. However, at ambient temperatures of 32.5
      C and above, untreated ovariectomized rats exhibited higher core temperatures
      compared with estradiol-treated rats. Thus, estradiol-17beta treatment enhanced
      the maintenance of core temperature during heat exposure. These findings support
      the hypothesis that estrogen withdrawal increases the sensitivity of
      thermoregulatory neural pathways and modifies the activation of heat loss
      mechanisms.

PMID- 20051486
TI  - Pregnancy up-regulates intestinal calcium absorption and skeletal mineralization
      independently of the vitamin D receptor.
AB  - Without the vitamin D receptor (VDR), adult mammals develop reduced intestinal
      calcium absorption, rickets, and osteomalacia. Intestinal calcium absorption
      normally increases during pregnancy so that the mother can supply sufficient
      calcium to her fetuses. The maternal skeleton is rapidly resorbed during
      lactation to provide calcium needed for milk; that lost bone mineral content
      (BMC) is completely restored after weaning. We studied Vdr null mice to determine
      whether these adaptations during pregnancy and lactation require the VDR. Vdr
      nulls were severely rachitic at 10 wk of age on a normal diet. Pregnancy induced
      a 158% increase in Vdr null BMC to equal the pregnant wild-type (WT) value.
      Lactation caused BMC losses that were equal in Vdr nulls and WT. Vdr nulls
      recovered after weaning to a BMC 50% higher than before pregnancy and equal to
      WT. Additional analyses showed that during pregnancy, duodenal (45)Ca absorption
      increased in Vdr nulls, secondary hyperparathyroidism lessened, bone turnover
      markers decreased, and osteoid became fully mineralized. A genome-wide microarray
      analysis of duodenal RNA found marked reduction of Trpv6 in Vdr nulls at baseline
      but a 13.5-fold increase during pregnancy. Calbindin D-9K (S100g) and Ca(2+)
      ATPase (Pmca1) were not altered by pregnancy. Several other solute transporters
      increased during pregnancy in Vdr nulls. In summary, Vdr nulls adapt to pregnancy
      by up-regulating duodenal Trpv6 and intestinal (45)Ca absorption, thereby
      enabling rapid normalization of BMC during pregnancy. These mice lactate normally
      and fully restore BMC after weaning. Therefore, VDR is not required for the
      skeletal adaptations during pregnancy, lactation, and after weaning.

PMID- 20051487
TI  - RFamide-related peptide and messenger ribonucleic acid expression in mammalian
      testis: association with the spermatogenic cycle.
AB  - RFamide-related peptide (RFRP), the mammalian homolog of avian gonadotropin
      inhibitory hormone, has a pronounced suppressive action on the reproductive axis
      across species. In mammals, RFRP acts directly on GnRH neurons, and likely at the
      level of the pituitary, to inhibit gonadotropin secretion. In the present study,
      we examined whether RFRP might act outside of mammalian brain on reproductive
      tissues directly. Using RT-PCR and in situ hybridization, we found that both RFRP
      and its receptors [G protein-coupled receptor (GPR) 147 and GPR74] are expressed
      in the testis of Syrian hamster. These results were confirmed and extended using
      double- and triple-label immunohistochemistry. RFRP expression was observed in
      spermatocytes and in round to early elongated spermatids. Significant expression
      of RFRP was not seen in Leydig cells. GPR147 protein was observed in myoid cells
      in all stages of spermatogenesis, pachytene spermatocytes, maturation division
      spermatocytes, and in round and late elongated spermatids. GPR74 proteins only
      appeared in late elongated spermatids. Additionally, we found that RFRP and its
      receptor mRNA are markedly altered by day length and reproductive condition.
      These findings highlight a possible novel autocrine and/or paracrine role for
      RFRP in Syrian hamster testis, potentially contributing to the differentiation of
      spermatids during spermiogenesis.

PMID- 20051488
TI  - Gonadotropin-releasing hormone-I-mediated activation of progesterone receptor
      contributes to gonadotropin alpha-subunit expression in mouse gonadotrophs.
AB  - In pituitary cells, cross talk between GnRH-I and the progesterone receptor
      accentuates gonadotropin production. We show that GnRH-I activates a progesterone
      response element (PRE)-driven luciferase reporter gene at 8 h and gonadotropin
      alpha-subunit (gsu alpha) gene expression at 24 h in two mouse gonadotrope cell
      lines, alpha T3-1 and L beta T2. In alpha T3-1 cells, progesterone had an
      additive effect on GnRH-I-induced PRE-luciferase reporter gene activity but not
      on GSU alpha mRNA levels. However, progesterone had no synergistic effect on the
      GnRH-I-induced expression of these genes in L beta T2 cells. Up-regulation of the
      PRE-luciferase reporter gene by GnRH-I was attenuated by pretreatment with
      protein kinase A (H89) and protein kinase C (GF109203X) inhibitors in both cell
      lines, whereas only GF109203X inhibited GnRH-I-induced GSU alpha mRNA levels.
      Most important, in both cell lines within the same time frame, knockdown of
      progesterone receptor levels by small interfering RNA reduced GnRH-I activation
      of GSU alpha mRNA levels by approximately 40%. We conclude that the effect of
      GnRH-I on gsu alpha expression in both alpha T3-1 and L beta T2 cells is mediated
      by ligand-independent activation of progesterone receptor and that this
      contributes to the self-priming effect of GnRH-I in the pituitary.

PMID- 20051489
TI  - Differential release of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases by human granulosa-lutein cells and ovarian leukocytes.
AB  - Tissue reorganization during ovulation and corpus luteum formation involves a
      coordinated action of matrix metalloproteinases (MMPs) and tissue MMP inhibitors
      (TIMPs). In this study we investigated the cellular source of ovarian MMPs and
      TIMPs. Cells isolated from the preovulatory human follicle were cultured after
      immunobead depletion of CD45-expressing cells, which allowed differential
      assessment of leukocyte and granulosa-lutein cell fractions. Secretion of MMP-9
      by follicular fluid-derived cells was associated with the presence of leukocytes.
      Granulosa-lutein cells synthesized low levels of MMP-9 but failed to secrete this
      enzyme that presumably accumulated in the cytoplasm, indicated by an increased
      MMP-9 expression of luteinized cells in sectioned midluteal phase corpora lutea.
      Synthesis and secretion of TIMP by follicular fluid-derived cells was associated
      with granulosa-lutein cells. TIMPs derived by granulosa-lutein cells failed to
      inhibit MMP-related pericellular proteolysis. The findings support a two-cell
      model of periovulatory MMP/TIMP release, in which leukocytes secrete MMPs and
      granulosa-lutein cells release TIMP, suggesting that there exists an intriguing
      interaction among cells that intertwingle during ovulation and corpus luteum
      formation.

PMID- 20051490
TI  - The nuclear receptor corepressor has organizational effects within the developing
      amygdala on juvenile social play and anxiety-like behavior.
AB  - Nuclear receptor function on DNA is regulated by the balanced recruitment of
      coregulatory complexes. Recruited proteins that increase gene expression are
      called coactivators, and those that decrease gene expression are called
      corepressors. Little is known about the role of corepressors, such as nuclear
      receptor corepressor (NCoR), on the organization of behavior. We used real-time
      PCR to show that NCoR mRNA levels are sexually dimorphic, that females express
      higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and
      that NCoR mRNA levels are reduced by estradiol treatment. To investigate the
      functional role of NCoR on juvenile social behavior, we infused small interfering
      RNA targeted against NCoR within the developing rat amygdala and assessed the
      enduring impact on juvenile social play behavior, sociability, and anxiety-like
      behavior. As expected, control males exhibited higher levels of juvenile social
      play than control females. Reducing NCoR expression during development further
      increased juvenile play in males only. Interestingly, decreased NCoR expression
      within the developing amygdala had lasting effects on increasing juvenile anxiety
      like behavior in males and females. These data suggest that the corepressor NCoR
      functions to blunt sex differences in juvenile play behavior, a sexually
      dimorphic and hormone-dependent behavior, and appears critical for appropriate
      anxiety-like behavior in juvenile males and females.

PMID- 20051492
TI  - Increasing physical activity: a step toward controlling metabolic syndrome.

PMID- 20051491
TI  - Enzymatic and nonenzymatic functions of viral RNA-dependent RNA polymerases
      within oligomeric arrays.
AB  - Few antivirals are effective against positive-strand RNA viruses, primarily
      because the high error rate during replication of these viruses leads to the
      rapid development of drug resistance. One of the favored current targets for the
      development of antiviral compounds is the active site of viral RNA-dependent RNA
      polymerases. However, like many subcellular processes, replication of the genomes
      of all positive-strand RNA viruses occurs in highly oligomeric complexes on the
      cytosolic surfaces of the intracellular membranes of infected host cells. In this
      study, catalytically inactive polymerases were shown to participate productively
      in functional oligomer formation and catalysis, as assayed by RNA template
      elongation. Direct protein transduction to introduce either active or inactive
      polymerases into cells infected with mutant virus confirmed the structural role
      for polymerase molecules during infection. Therefore, we suggest that targeting
      the active sites of polymerase molecules is not likely to be the best antiviral
      strategy, as inactivated polymerases do not inhibit replication of other viruses
      in the same cell and can, in fact, be useful in RNA replication complexes. On the
      other hand, polymerases that could not participate in functional RNA replication
      complexes were those that contained mutations in the amino terminus, leading to
      altered contacts in the folded polymerase and mutations in a known polymerase
      polymerase interaction in the two-dimensional protein lattice. Thus, the
      functional nature of multimeric arrays of RNA-dependent RNA polymerase supplies a
      novel target for antiviral compounds and provides a new appreciation for
      enzymatic catalysis on membranous surfaces within cells.

PMID- 20051493
TI  - Firing probability and mean firing rates of human muscle vasoconstrictor neurones
      are elevated during chronic asphyxia.
AB  - Elevated muscle sympathetic nerve activity (MSNA) features in many cardiovascular
      diseases, but how this sympathoexcitation is brought about differs across
      pathologies. Unitary recordings from post-ganglionic muscle vasoconstrictor
      neurones in human subjects have shown that the augmented MSNA in the obstructive
      sleep apnoea syndrome (OSAS) is associated with an increase in firing probability
      and mean firing rate, and an increase in multiple within-burst firing. Here we
      characterize the firing properties of muscle vasoconstrictor neurones in patients
      with chronic obstructive pulmonary disease (COPD), who are chronically asphyxic.
      We tested the hypothesis that this elevated chemical drive would shift the firing
      pattern from that seen in healthy subjects to that seen in OSAS. The mean firing
      probability (52%) and mean firing rate (0.92 Hz) of 17 muscle vasoconstrictor
      neurones recorded in COPD were comparable to those previously recorded in OSAS
      (51% and 0.96 Hz), but significantly higher than those recorded in a group of
      healthy subjects with high levels of resting MSNA (35% and 0.33 Hz). In COPD
      single neurones fired once in 63% of cardiac intervals, comparable to OSAS (59%),
      but significantly lower than in the healthy group (78%). Conversely, single
      neurones fired twice in 25% of cardiac intervals, similar to OSAS (27%), but
      significantly higher than in the healthy group (18%). We conclude that the
      chronic asphyxia associated with COPD results in an increase in the firing
      probability and mean firing frequency of muscle vasoconstrictor neurones and
      causes a shift towards multiple firing, reflecting an increase in central muscle
      vasoconstrictor drive.

PMID- 20051494
TI  - Identification of the current generator underlying cholinergically induced gamma
      frequency field potential oscillations in the hippocampal CA3 region.
AB  - Gamma frequency oscillations (30-100 Hz) are prominent in the hippocampal EEG
      signal during active network states. An intrahippocampal gamma generator has been
      identified in the CA3 region. To understand the mechanism of oscillation
      generation, both the rhythm and the current generators must be identified. While
      earlier work has elucidated mechanisms of rhythm generation, little attention has
      been given to identifying the CA3 gamma current generator. Here, we aimed to
      identify a current generator underlying cholinergically induced gamma frequency
      oscillations in vitro. To this end, we analysed the instantaneous fluctuations in
      the wavelet amplitude of the field potential oscillation recorded in the stratum
      pyramidale, and concomitantly recorded action potentials and synaptic input in
      individual, anatomically identified neurons. The data revealed that perisomatic
      inhibitory currents in pyramidal cells generated the majority of the field
      potential. Pyramidal cell action currents also contributed to the field. In
      contrast, we found no evidence that excitatory currents contribute significantly
      to the field oscillations in this model. The moment-by-moment analysis of the
      dynamics of the field potential presented here provides insight into the distinct
      contributions of synaptic and action currents to the EEG signal and sheds light
      on the changing balance of excitation and inhibition during cholinergically
      induced gamma frequency oscillations.

PMID- 20051495
TI  - Zebrafish (Danio rerio) gill neuroepithelial cells are sensitive chemoreceptors
      for environmental CO2.
AB  - Adult zebrafish exhibit hyperventilatory responses to absolute environmental
      CO(2) levels as low as 0.13% ( mmHg), more than an order of magnitude lower than
      the typical arterial levels (40 mmHg) monitored by the mammalian carotid body.
      The sensory basis underlying the ability of fish to detect and respond to low
      ambient CO(2) levels is not clear. Here, we show that the neuroepithelial cells
      (NECs) of the zebrafish gill, known to sense O(2) levels, also respond to low
      levels of CO(2). An electrophysiological characterization of this response using
      both current and voltage clamp protocols revealed that for increasing CO(2)
      levels, a background K(+) channel was inhibited, resulting in a partial pressure
      dependent depolarization of the NEC. To elucidate the signalling pathway
      underlying K(+) channel inhibition, we used immunocytochemistry to show that
      these NECs express carbonic anhydrase (CA), an enzyme involved in CO(2) sensing
      in the mammalian carotid body. Further, the NEC response to CO(2) (magnitude of
      membrane depolarization and time required to achieve maximal response), under
      conditions of constant pH, was reduced by 50% by the CA-inhibitor acetazolamide.
      This suggests that the CO(2) detection mechanism involves an intracellular sensor
      that is responsive to the rate of acidification associated with the hydration of
      CO(2) and which does not require a change of extracellular pH. Because some cells
      that were responsive to increasing also responded to hypoxia with membrane
      depolarization, the present results demonstrate that a subset of the NECs in the
      zebrafish gill are bimodal sensors of CO(2) and O(2).

PMID- 20051498
TI  - Safflower and olive oil dietary treatments rescue aberrant embryonic arachidonic
      acid and nitric oxide metabolism and prevent diabetic embryopathy in rats.
AB  - Aberrant arachidonic acid and nitric oxide (NO) metabolic pathways are involved
      in diabetic embryopathy. Previous works have found diminished concentrations of
      PGE(2) and PGI(2) in embryos from diabetic rats, and that PGI(2) is capable of
      increasing embryonic PGE(2) concentrations through the activation of the nuclear
      receptor PPARdelta. PPARdelta activators are lipid molecules such as oleic and
      linoleic acids, present in high concentrations in olive and safflower oils,
      respectively. The aim of this study was to analyze the capability of dietary
      supplementation with either 6% olive or 6% safflower oils to regulate PGE(2),
      PGI(2) and NO concentrations in embryos and deciduas from control and diabetic
      rats during early organogenesis. Diabetes was induced by a single injection of
      streptozotocin (55 mg/kg) 1 week before mating. Animals were fed with the oil
      supplemented diets from Days 0.5 to 10.5 of gestation. PGI(2) and PGE(2) were
      measured by EIA and NO through the evaluation of its stable metabolites nitrates
      nitrites in 10.5 day embryos and deciduas. We found that the olive and safflower
      oil-supplemented treatments highly reduced resorption and malformation rates in
      diabetic animals, and that they were able to prevent maternal diabetes-induced
      alterations in embryonic and decidual PGI(2) and PGE(2) concentrations. Moreover,
      these dietary treatments prevented NO overproduction in embryos and deciduas from
      diabetic rats. These data indicate that in maternal diabetes both the embryo and
      the decidua benefit from the olive and safflower oil supplementation probably
      through mechanisms that involve the rescue of aberrant prostaglandin and NO
      generation and that prevent developmental damage during early organogenesis.

PMID- 20051497
TI  - Increased vasopressin transmission from the paraventricular nucleus to the
      rostral medulla augments cardiorespiratory outflow in chronic intermittent
      hypoxia-conditioned rats.
AB  - A co-morbidity of sleep apnoea is hypertension associated with elevated
      sympathetic nerve activity (SNA) which may result from conditioning to chronic
      intermittent hypoxia (CIH). Our hypothesis is that SNA depends on input to the
      rostral ventrolateral medulla (RVLM) from neurons in the paraventricular nucleus
      (PVN) that release arginine vasopressin (AVP) and specifically, that increased
      SNA evoked by CIH depends on this excitatory input. In two sets of
      neuroanatomical experiments, we determined if AVP neurons project from the PVN to
      the RVLM and if arginine vasopressin (V(1A)) receptor expression increases in the
      RVLM after CIH conditioning (8 h per day for 10 days). In the first set, cholera
      toxin beta subunit (CT-beta) was microinjected into the RVLM to retrogradely
      label the PVN neurons. Immunohistochemical staining demonstrated that 14.6% of CT
      beta-labelled PVN neurons were double-labelled with AVP. In the second set,
      sections of the medulla were immunolabelled for V(1A) receptors, and the V(1A)
      receptor-expressing cell count was significantly greater in the RVLM (P < 0.01)
      and in the neighbouring rostral ventral respiratory column (rVRC) from CIH- than
      from room air (RA)-conditioned rats. In a series of physiological experiments, we
      determined if blocking V(1A) receptors in the medulla would normalize blood
      pressure in CIH-conditioned animals and attenuate its response to disinhibition
      of PVN. Blood pressure (BP), heart rate (HR), diaphragm (D(EMG)) and genioglossus
      muscle (GG(EMG)) activity were recorded in anaesthetized, ventilated and
      vagotomized rats. The PVN was disinhibited by microinjecting a GABA(A) receptor
      antagonist, bicuculline (BIC, 0.1 nmol), before and after blocking V(1A)
      receptors within the RVLM and rVRC with SR49059 (0.2 nmol). In RA-conditioned
      rats, disinhibition of the PVN increased BP, HR, minute D(EMG) and GG(EMG)
      activity and these increases were attenuated after blocking V(1A) receptors. In
      CIH-conditioned rats, a significantly greater dose of blocker (0.4 nmol) was
      required to blunt these physiological responses (P < 0.05). Further, this dose
      normalized the baseline BP. In summary, AVP released by a subset of PVN neurons
      modulates cardiorespiratory output via V(1A) receptors in the RVLM and rVRC, and
      increased SNA in CIH-conditioned animals depends on up-regulation of V(1A)
      receptors in the RVLM.

PMID- 20051499
TI  - Imaging and ultrasound-guided steroid injection of internal oblique muscle
      strains in baseball pitchers.
AB  - BACKGROUND: Internal oblique muscle injuries are common in professional baseball
      pitchers and may require a prolonged convalescence of up to 10 weeks. Most
      strains can be diagnosed clinically, but imaging can be helpful to assess the
      severity of injury, which may predict recovery and return to play. HYPOTHESIS:
      Ultrasound-guided injection of steroid and local anesthetic into the muscle tear
      can speed recovery and subsequent return to play. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Three professional baseball pitchers with acute
      tears of the internal oblique muscle confirmed by magnetic resonance imaging
      underwent ultrasound-guided injection of steroid and local anesthetic. RESULTS:
      All 3 patients experienced significant pain relief within a few days of the
      injection and were able to pitch at full speed within 3 weeks of injury (mean, 21
      days) and return to able status by 5 weeks (mean, 30.7 days). The 3 athletes
      continue to pitch in Major League Baseball 36 months, 36 months, and 14 months,
      respectively, after injury, and none have sustained reinjury during this time.
      CONCLUSION: Therapeutic injection of steroids and anesthetic under ultrasound
      guidance appears to speed recovery and rehabilitation in professional baseball
      pitchers with acute side strains.

PMID- 20051500
TI  - Relationship between low back pain and competitive sports activities during
      youth.
AB  - BACKGROUND: Low back pain is a significant problem not only for the adult, but
      also during youth. However, the relationship between low back pain during youth
      and the duration or types of competitive sports has not been clarified.
      HYPOTHESIS: Low back pain during youth is associated with the duration and types
      of competitive sports. STUDY DESIGN: Cross-sectional study; Level of evidence, 4.
      METHODS: Study participants were 4667 new university students who, from 2004 to
      2006, answered a questionnaire concerning low back pain and their participation
      in competitive sports. The participants were divided into a "no" group (NO), a
      middle group (MID), and a high group (HI) based on the duration of participation
      in competitive sports. The answers to the questionnaire were analyzed using the
      Cochran-Mantel-Haenszel test. Furthermore, we selected students who had
      participated in the same sport for 5 or more years and categorized the students
      according to the type of sport. Differences in low back pain among the groups
      were analyzed using logistic regression with the NO group as the reference group.
      RESULTS: There were statistically significant linear associations in the NO, MID,
      and HI groups, with 50.0%, 61.8%, and 71.7%, respectively, of the students
      experiencing low back pain. Among the NO, MID, and HI groups, 4.4%, 5.7%, 9.6%,
      respectively, had experienced school absence due to low back pain; and 4.0%,
      8.5%, and 14.6%, respectively had low back pain with associated lower extremity
      pain and numbness. All 8 sports groups that were analyzed had experienced low
      back pain significantly higher than the NO group, and the odds ratios differed by
      sport with the highest (3.8) for the volleyball group. CONCLUSION: Excessive
      exposure to competitive sports activities during youth was associated with low
      back pain and symptoms in the lower extremities, with the severity varying with
      the sport. To reduce low back pain in youth, factors that may be causing low back
      pain, such as sport-specific postures and motions, need to be investigated.

PMID- 20051501
TI  - Factors involved in the development of osteoarthritis after anterior cruciate
      ligament surgery.
AB  - BACKGROUND: The incidence of osteoarthritis after anterior cruciate ligament
      reconstruction is disturbingly high, with reports of nearly 50% of patients
      developing mild to moderate osteoarthritis 6 years after surgery. Few studies
      have assessed the factors involved in the development of osteoarthritis.
      HYPOTHESIS: The following 10 factors will be found to be predictive of
      osteoarthritis: meniscectomy, chondral damage, patellar tendon grafting, age at
      surgery, time delay between injury and surgery, type and intensity of postsurgery
      sport, quadriceps strength, hamstring strength, quadriceps-to-hamstring strength
      ratio, and residual joint laxity. STUDY DESIGN: Cohort study (prognosis); Level
      of evidence, 1. METHODS: Fifty-six subjects with anterior cruciate ligament
      reconstruction were followed for 6 years after surgery. Assessment included KT
      1000 arthrometer testing, isokinetic strength testing, a return-to-sport
      questionnaire, and a radiograph assessment. A discriminant analysis was performed
      to assess which of the 10 factors could discriminate between those patients who
      developed tibiofemoral and patellofemoral osteoarthritis and those who did not.
      RESULTS: Five factors were found to be predictive of tibiofemoral osteoarthritis.
      Meniscectomy (r = .72) and chondral damage (r = .41) were the strongest
      discriminators, followed by patellar tendon grafting (r = .37) (chi(2) [7, n =
      56] = 25.48; P = .001). Weak quadriceps (r = .39) and low quadriceps-to-hamstring
      strength ratios (r = .6) were very close discriminators (chi(2) [8, n = 42] =
      15.02; P = .059). For patellofemoral osteoarthritis, meniscectomy (r = .45),
      chondral damage (r = .75), and age at surgery (r = .65) were predictors or close
      predictors (chi(2) [7, n = 54] = 13.30; P = .065). CONCLUSION: As not all 10
      factors studied were predictive of osteoarthritis, the hypothesis was only
      partially proven. Preventing further meniscal and chondral damage in patients
      with anterior cruciate ligament deficiency is critical. Grafting using the
      hamstring tendons and restoration of quadriceps-to-hamstring strength balance are
      associated with less osteoarthritis.

PMID- 20051502
TI  - Marking the 50th anniversary of the Platt Report: from exclusion, to toleration
      and parental participation in the care of the hospitalized child.
AB  - This paper commemorates the 50th anniversary of the Platt Report in the United
      Kingdom and traces the history of parental hospital visiting in relation to its
      recommendation that, 'Parents should be allowed to visit whenever they can, and
      to help as much as possible with the care of the child' (Ministry of Health,
      1959: 38). It tracks how this goal was achieved and identifies how parents moved
      from being excluded towards being tolerated and finally accepted as participants
      in their child's care. This is set against a backdrop of changes in society,
      systems of healthcare and nurse education as well as trends in the care of the
      hospitalized children from national and international perspectives. It concludes
      that if we are to meet the needs of hospitalized children in the 21st century,
      the focus of research must now shift towards seeking their perspectives on care.

PMID- 20051503
TI  - Re: Double-bundle anterior cruciate ligament reconstruction: a computer-assisted
      orthopaedic surgery study.

PMID- 20051504
TI  - Re: The 1:1 versus the 2:2 tunnel-drilling technique: optimization of fixation
      strength and stiffness in an all-inside double-bundle anterior cruciate ligament
      reconstruction--a biomechanical study.

PMID- 20051505
TI  - Re: Axial linear patellar displacement: a new measurement of patellofemoral
      congruence.

PMID- 20051506
TI  - Re: Current concepts in the diagnosis and treatment of osteochondral lesions of
      the ankle.

PMID- 20051507
TI  - Success or failure?

PMID- 20051508
TI  - Does intensive rehabilitation permit early return to sport without compromising
      the clinical outcome after arthroscopic autologous chondrocyte implantation in
      highly competitive athletes?
AB  - BACKGROUND: Despite improvement in treatment for articular cartilage lesions,
      prolonged recovery still precludes early return to competitive sports. The
      challenge of postoperative rehabilitation is to optimize return to preinjury
      activities without jeopardizing the graft. HYPOTHESIS: Intensive rehabilitation
      after second-generation arthroscopic autologous cartilage implantation
      (Hyalograft C) facilitates graft maturation and safely allows for early return to
      competition without jeopardizing clinical outcome at longer follow-up. STUDY
      DESIGN: Cohort study; Level of evidence, 3. METHODS: The outcome of 31
      competitive male athletes with International Cartilage Repair Society grade III
      IV cartilaginous lesions of the medial or lateral femoral condyle or trochlea
      were evaluated at 1-, 2-, and 5-year follow-up. The athletic cohort was compared
      with a similar control cohort of 34 nonathletic patients who were treated with
      autologous chondrocyte implantation. The athletic cohort followed a 4-phase
      intensive rehabilitation protocol. Eleven of the patients in this cohort were
      also treated with an isokinetic exercise program and on-field rehabilitation. The
      patients in the control cohort completed only phase 1 of rehabilitation. RESULTS:
      When comparing the 2 groups, a greater improvement in the group of athletes was
      achieved at 5-year follow-up (P = .037) in the self-assessment of quality of life
      and International Knee Documentation Committee subjective evaluation at 12 months
      and at 5 years of follow-up (P = .001 and P = .002, respectively). When analyzing
      the return to sports activity, 80.6% of the athletes returned to their previous
      activity level in 12.4 +/- 1.6 months; athletes treated with the on-field
      rehabilitation and isokinetic exercise program had faster recovery and an even
      earlier return to competition (10.6 +/- 2.0 months). CONCLUSION: For optimal
      results, autologous chondrocyte implantation rehabilitation should not only
      follow but also facilitate the process of graft maturation. Intensive
      rehabilitation may safely allow a faster return to competition and also influence
      positively the clinical outcome at medium-term follow-up.

PMID- 20051509
TI  - Does the graft source really matter in the outcome of patients undergoing
      anterior cruciate ligament reconstruction? An evaluation of autograft versus
      allograft reconstruction results: a systematic review.
AB  - BACKGROUND: Despite the large number of anterior cruciate ligament
      reconstructions performed each year, there remains a significant controversy
      regarding the effect of the graft source on the functional outcome of patients.
      HYPOTHESIS: There is no difference in outcomes of autograft versus allograft
      anterior cruciate ligament reconstructions. STUDY DESIGN: Systematic review.
      METHODS: The authors systematically identified prospective studies (Oxford level
      of evidence I or II only) that included autograft patients, allograft patients,
      or both. Objective outcomes that were reported were meta-analyzed; this included
      pivot-shift results, KT-1000 arthrometer results, International Knee
      Documentation Committee (IKDC) scores, Lysholm Scores, graft failures, and
      postoperative complications. Two statistical analyses were performed. First a
      primary statistical analysis was performed comparing pooled autograft data (bone
      patellar-tendon bone and hamstrings combined) and pooled allograft data (bone
      patellar-tendon bone and hamstrings combined). To have a more comprehensive
      understanding of the differences between each specific graft source, a secondary
      analysis was performed without pooling the data; this directly compared the 4
      types of graft sources that were studied. RESULTS: Over 400 scientific
      manuscripts were initially reviewed; 31 manuscripts fulfilled all of the search
      criteria. There were very few statistically significant differences between
      autograft and allograft tissue. The KT-1000 arthrometer laxity testing revealed a
      mean of 1.4 +/- 0.2 mm (weighted mean +/- standard error of the mean) for the
      allograft group compared with 1.8 +/- 0.1 mm for the autograft group (t = 2.40; P
      <.02). However, this difference was only for the mean score; there was no
      statistical significance when considering KT-1000 arthrometer measurements of
      greater than 3 or 5 mm. The percentage of patients receiving a final IKDC score
      of "A" (normal knee) was statistically significant for allograft tissue (43.9% +/
      5.5%) versus autograft tissue (28.2% +/- 1.0%) reconstructions. There was no
      statistically significant difference between the percentages of IKDC scores of A
      or B for patients receiving pooled allograft (82.9% +/- 4.2%) versus pooled
      autograft (87.2% +/- 0.9%) anterior cruciate ligament reconstruction (t = 1.01; P
      > .1). The graft failure rate was 4.7 +/- 0.5 per 100 for autograft
      reconstructions and 8.2 +/- 2.1 per 100 allograft reconstructions; although this
      may represent a trend, it is not statistically significant (t = 1.49; P > .1).
      The complication rate was slightly higher for autograft reconstructions at 3.5 +/
      0.4 complications per 100 autograft reconstructions compared with 2.4 +/- 1.1
      complications per 100 allograft reconstructions, but not significant (t = 1.41; P
      > .1). CONCLUSION: After a comprehensive examination and statistical analysis of
      the modern literature, the authors could not identify an individual graft source
      that was clearly superior to the other graft sources. This led them to believe
      that, with currently available data, the graft source has a minimal effect on the
      outcome of patients undergoing anterior cruciate ligament reconstruction.

PMID- 20051513
TI  - Lysine 63-linked polyubiquitination of the dopamine transporter requires WW3 and
      WW4 domains of Nedd4-2 and UBE2D ubiquitin-conjugating enzymes.
AB  - RNA interference screen previously revealed that a HECT-domain E3 ubiquitin
      ligase, neuronal precursor cell expressed, developmentally down-regulated 4-2
      (Nedd4-2), is necessary for ubiquitination and endocytosis of the dopamine
      transporter (DAT) induced by the activation of protein kinase C (PKC). To further
      confirm the role of Nedd4-2 in DAT ubiquitination and endocytosis, we
      demonstrated that the depletion of Nedd4-2 by two different small interfering RNA
      (siRNA) duplexes suppressed PKC-dependent ubiquitination and endocytosis of DAT
      in human and porcine cells, whereas knock-down of a highly homologous E3 ligase,
      Nedd4-1, had no effect on DAT. The abolished DAT ubiquitination in Nedd4-2
      depleted cells was rescued by expression of recombinant Nedd4-2. Moreover,
      overexpression of Nedd4-2 resulted in increased PKC-dependent ubiquitination of
      DAT. Mutational inactivation of the HECT domain of Nedd4-2 inhibited DAT
      ubiquitination and endocytosis. Structure-function analysis of Nedd4-2-mediated
      DAT ubiquitination revealed that the intact WW4 domain and to a lesser extent WW3
      domain are necessary for PKC-dependent DAT ubiquitination. Moreover, a fragment
      of the Nedd4-2 molecule containing WW3, WW4, and HECT domains was sufficient for
      fully potentiating PKC-dependent ubiquitination of DAT. Analysis of DAT
      ubiquitination using polyubiquitin chain-specific antibodies showed that DAT is
      mainly conjugated with Lys(63)-linked ubiquitin chains. siRNA analysis
      demonstrated that this polyubiquitination is mediated by Nedd4-2 cooperation with
      UBE2D and UBE2L3 E2 ubiquitin-conjugating enzymes. The model is proposed whereby
      each ubiquitinated DAT molecule is modified by a single four-ubiquitin Lys(63)
      linked chain that can be conjugated to various lysine residues of DAT.

PMID- 20051514
TI  - NF45 and NF90 regulate HS4-dependent interleukin-13 transcription in T cells.
AB  - Expression of the cytokine interleukin-13 (IL13) is critical for Th2 immune
      responses and Th2-mediated allergic diseases. Activation of human IL13 expression
      involves chromatin remodeling and formation of multiple DNase I-hypersensitive
      sites throughout the locus. Among these, HS4 is detected in the distal IL13
      promoter in both naive and polarized CD4(+) T cells. We show herein that HS4 acts
      as a position-independent, orientation-dependent positive regulator of IL13
      proximal promoter activity in transiently transfected, activated human CD4(+)
      Jurkat T cells and primary murine Th2 cells. The 3'-half of HS4 (HS4-3') was
      responsible for IL13 up-regulation and bound nuclear factor (NF) 90 and NF45, as
      demonstrated by DNA affinity chromatography coupled with tandem mass
      spectrometry, chromatin immunoprecipitation, and gel shift analysis. Notably, the
      CTGTT NF45/NF90-binding motif within HS4-3' was critical for HS4-dependent up
      regulation of IL13 expression. Moreover, transfection of HS4-IL13 reporter
      vectors into primary, in vitro differentiated Th2 cells from wild-type, NF45(+/
      ), or NF90(+/-) mice showed that HS4 activity was exquisitely dependent on the
      levels of endogenous NF45 (and to a lesser degree NF90), because HS4-dependent
      IL13 expression was virtually abrogated in NF45(+/-) cells and reduced in NF90(+/
      ) cells. Collectively, our results identify NF45 and NF90 as novel regulators of
      HS4-dependent human IL13 transcription in response to T cell activation.

PMID- 20051515
TI  - The stress hormone corticosterone increases synaptic alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors via serum- and glucocorticoid
      inducible kinase (SGK) regulation of the GDI-Rab4 complex.
AB  - Corticosterone, the major stress hormone, plays an important role in regulating
      neuronal functions of the limbic system, although the cellular targets and
      molecular mechanisms of corticosteroid signaling are largely unknown. Here we
      show that a short treatment of corticosterone significantly increases alpha-amino
      3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic
      transmission and AMPAR membrane trafficking in pyramidal neurons of prefrontal
      cortex, a key region involved in cognition and emotion. This enhancing effect of
      corticosterone is through a mechanism dependent on Rab4, the small GTPase
      controlling receptor recycling between early endosome and plasma membrane.
      Guanosine nucleotide dissociation inhibitor (GDI), which regulates the cycle of
      Rab proteins between membrane and cytosol, forms an increased complex with Rab4
      after corticosterone treatment. Corticosterone also triggers an increased GDI
      phosphorylation at Ser-213 by the serum- and glucocorticoid-inducible kinase
      (SGK). Moreover, AMPAR synaptic currents and surface expression and their
      regulation by corticosterone are altered by mutating Ser-213 on GDI. These
      results suggest that corticosterone, via SGK phosphorylation of GDI at Ser-213,
      increases the formation of GDI-Rab4 complex, facilitating the functional cycle of
      Rab4 and Rab4-mediated recycling of AMPARs to the synaptic membrane. It provides
      a potential mechanism underlying the role of corticosteroid stress hormone in up
      regulating excitatory synaptic efficacy in cortical neurons.

PMID- 20051516
TI  - Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in
      intestinal and tracheal Cl- transport.
AB  - The KCNE3 beta-subunit constitutively opens outwardly rectifying KCNQ1 (Kv7.1)
      K(+) channels by abolishing their voltage-dependent gating. The resulting
      KCNQ1/KCNE3 heteromers display enhanced sensitivity to K(+) channel inhibitors
      like chromanol 293B. KCNE3 was also suggested to modify biophysical properties of
      several other K(+) channels, and a mutation in KCNE3 was proposed to underlie
      forms of human periodic paralysis. To investigate physiological roles of KCNE3,
      we now disrupted its gene in mice. kcne3(-/-) mice were viable and fertile and
      displayed neither periodic paralysis nor other obvious skeletal muscle
      abnormalities. KCNQ1/KCNE3 heteromers are present in basolateral membranes of
      intestinal and tracheal epithelial cells where they might facilitate
      transepithelial Cl(-) secretion through basolateral recycling of K(+) ions and by
      increasing the electrochemical driving force for apical Cl(-) exit. Indeed, cAMP
      stimulated electrogenic Cl(-) secretion across tracheal and intestinal epithelia
      was drastically reduced in kcne3(-/-) mice. Because the abundance and subcellular
      localization of KCNQ1 was unchanged in kcne3(-/-) mice, the modification of
      biophysical properties of KCNQ1 by KCNE3 is essential for its role in intestinal
      and tracheal transport. Further, these results suggest KCNE3 as a potential
      modifier gene in cystic fibrosis.

PMID- 20051517
TI  - Cytosines, but not purines, determine recombination activating gene (RAG)-induced
      breaks on heteroduplex DNA structures: implications for genomic instability.
AB  - The sequence specificity of the recombination activating gene (RAG) complex
      during V(D)J recombination has been well studied. RAGs can also act as structure
      specific nuclease; however, little is known about the mechanism of its action.
      Here, we show that in addition to DNA structure, sequence dictates the pattern
      and efficiency of RAG cleavage on altered DNA structures. Cytosine nucleotides
      are preferentially nicked by RAGs when present at single-stranded regions of
      heteroduplex DNA. Although unpaired thymine nucleotides are also nicked, the
      efficiency is many fold weaker. Induction of single- or double-strand breaks by
      RAGs depends on the position of cytosines and whether it is present on one or
      both of the strands. Interestingly, RAGs are unable to induce breaks when adenine
      or guanine nucleotides are present at single-strand regions. The nucleotide
      present immediately next to the bubble sequence could also affect RAG cleavage.
      Hence, we propose "C((d))C((S))C((S))" (d, double-stranded; s, single-stranded)
      as a consensus sequence for RAG-induced breaks at single-/double-strand DNA
      transitions. Such a consensus sequence motif is useful for explaining RAG
      cleavage on other types of DNA structures described in the literature. Therefore,
      the mechanism of RAG cleavage described here could explain facets of chromosomal
      rearrangements specific to lymphoid tissues leading to genomic instability.

PMID- 20051518
TI  - The anti-apoptotic protein BCL2L1/Bcl-xL is neutralized by pro-apoptotic
      PMAIP1/Noxa in neuroblastoma, thereby determining bortezomib sensitivity
      independent of prosurvival MCL1 expression.
AB  - Neuroblastoma is the most frequent extracranial solid tumor in children. Here, we
      report that the proteasome inhibitor bortezomib (PS-341, Velcade) activated the
      pro-apoptotic BH3-only proteins PMAIP1/Noxa and BBC3/Puma and induced
      accumulation of anti-apoptotic MCL1 as well as repression of anti-apoptotic
      BCL2L1/Bcl-xL. Retroviral expression of Bcl-xL, but not of MCL1, prevented
      apoptosis by bortezomib. Gene knockdown of Noxa by shRNA technology significantly
      reduced apoptosis, whereas Puma knockdown did not affect cell death kinetics.
      Immunoprecipitation revealed that endogenous Noxa associated with both, Bcl-xL
      and MCL1, suggesting that in neuronal cells Noxa can neutralize Bcl-xL,
      explaining the pronounced protective effect of Bcl-xL. Tetracycline-regulated
      Noxa expression did not trigger cell death per se but sensitized to bortezomib
      treatment in a dose-dependent manner. This implies that the induction of Noxa is
      necessary but not sufficient for bortezomib-induced apoptosis. We conclude that
      MCL1 steady-state expression levels do not affect sensitivity to proteasome
      inhibitor treatment in neuronal tumor cells, and that both the repression of Bcl
      xL and the activation of Noxa are necessary for bortezomib-induced cell death.

PMID- 20051519
TI  - Identification of orthosteric and allosteric site mutations in M2 muscarinic
      acetylcholine receptors that contribute to ligand-selective signaling bias.
AB  - Muscarinic acetylcholine receptors contain at least one allosteric site that is
      topographically distinct from the acetylcholine, orthosteric binding site.
      Although studies have investigated the basis of allosteric modulation at these
      receptors, less is known about putative allosteric ligands that activate the
      receptor in their own right. We generated M(2) muscarinic acetylcholine receptor
      mutations in either the orthosteric site in transmembrane helices 3 and 6 (TM3
      and -6) or part of an allosteric site involving the top of TM2, the second
      extracellular (E2) loop, and the top of TM7 and investigated their effects on the
      binding and function of the novel selective (putative allosteric) agonists (AC-42
      (4-n-butyl-1-(4-(2-methylphenyl)-4-oxo-1-butyl)piperidine HCl), 77-LH-28-1 (1-(3
      (4-butyl-1-piperidinyl)propyl)-3,3-dihydro-2(1H)-quinolinone), and N
      desmethylclozapine) as well as the bitopic orthosteric/allosteric ligand, McN-A
      343 (4-(m-chlorophenyl-carbamoyloxy)-2-butynyltrimethylammonium). Four classes of
      agonists were identified, depending on their response to the mutations,
      suggesting multiple, distinct modes of agonist-receptor interaction.
      Interestingly, with the exception of 77-LH-28-1, allosteric site mutations had no
      effect on the affinity of any of the agonists tested, but some mutations in the
      E2 loop influenced the efficacy of both orthosteric and novel selective agonists,
      highlighting a role for this region of the receptor in modulating activation
      status. Two point mutations (Y104(3.33)A (Ballesteros and Weinstein numbers in
      superscript) in the orthosteric and Y177A in the allosteric site) unmasked ligand
      selective and signaling pathway-selective effects, providing evidence for the
      existence of pathway-specific receptor conformations. Molecular modeling of 77-LH
      28-1 and N-desmethylclozapine yielded novel binding poses consistent with the
      possibility that the functional selectivity of such agents may arise from a
      bitopic mechanism.

PMID- 20051520
TI  - The scaffold protein Shoc2/SUR-8 accelerates the interaction of Ras and Raf.
AB  - Shoc2/SUR-8 positively regulates Ras/ERK MAP kinase signaling by serving as a
      scaffold for Ras and Raf. Here, we examined the role of Shoc2 in the spatio
      temporal regulation of Ras by using a fluorescence resonance energy transfer
      (FRET)-based biosensor, together with computational modeling. In epidermal growth
      factor-stimulated HeLa cells, RNA-mediated Shoc2 knockdown reduced the
      phosphorylation of MEK and ERK with half-maximal inhibition, but not the
      activation of Ras. For the live monitoring of Ras binding to Raf, we utilized a
      FRET biosensor wherein Ras and the Ras-binding domain of Raf were connected
      tandemly and sandwiched with acceptor and donor fluorescent proteins for the FRET
      measurement. With this biosensor, we found that Shoc2 was required for the rapid
      interaction of Ras with Raf upon epidermal growth factor stimulation. To decipher
      the molecular mechanisms underlying the kinetics, we developed two computational
      models that might account for the action of Shoc2 in the Ras-ERK signaling. One
      of these models, the Shoc2 accelerator model, provided a reasonable explanation
      of the experimental observations. In this Shoc2 accelerator model, Shoc2
      accelerated both the association and dissociation of Ras-Raf interaction. We
      propose that Shoc2 regulates the spatio-temporal patterns of the Ras-ERK
      signaling pathway primarily by accelerating the Ras-Raf interaction.

PMID- 20051521
TI  - Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis.

PMID- 20051522
TI  - Disordered eating-related cognition and psychological flexibility as predictors
      of psychological health among college students.
AB  - The present cross-sectional study investigated the relation among disordered
      eating-related cognition, psychological flexibility, and poor psychological
      outcomes among a nonclinical college sample. As predicted, conviction of
      disordered eating-related cognitions was positively associated with general
      psychological ill-health and emotional distress in interpersonal contexts.
      Disordered eating-related cognition was also inversely related to psychological
      flexibility, which was inversely related to poor psychological health and
      emotional distress in interpersonal contexts. The combination of disordered
      eating-related cognition and psychological flexibility accounted for the
      proportion of variance of these poor psychological outcomes greater than
      disordered eating-related cognition alone. Finally, psychological flexibility
      accounted for the proportion of variance of these negative psychological
      variables greater than did disordered eating-related cognition.

PMID- 20051523
TI  - Cognitive and adaptive behavior outcomes of behavioral intervention for young
      children with intellectual disability.
AB  - Data from Norway were analyzed to evaluate early behavioral intervention for
      children with intellectual disabilities. The intervention group (n = 11) received
      approximately 10 hours per week of behavioral intervention; the eclectic
      comparison group (n = 14) received treatment as usual. After 1 year, changes in
      intelligence and adaptive behavior scores were statistically significant in favor
      of the behavioral intervention group (effect sizes of 1.13 for Intelligence
      quotient (IQ) change and .95 for change in adaptive behavior composite).
      Approximately 64% of the children in the behavioral intervention group met
      objective criteria for reliable change in IQ, whereas 14% in the eclectic
      comparison group did so. These results suggest that children with intellectual
      disability may profit from behavioral intervention typically provided for
      children with autism.

PMID- 20051524
TI  - Descriptive analyses of pediatric food refusal: the structure of parental
      attention.
AB  - Mealtime observations were conducted and occurrences of appropriate and
      inappropriate mealtime behavior and various forms of parental attention (e.g.,
      coaxing, reprimands) were recorded for 25 children admitted to an intensive
      feeding program and their parents. Using the data from the observations, lag
      sequential analyses were conducted to identify changes in the probability of
      child appropriate and inappropriate mealtime behavior before and after various
      forms of parental attention. A combination of univariate and repeated measures
      ANOVAs using frequency of child behavior were also conducted to corroborate
      conclusions drawn from the visual analysis of individual participant data.
      Results showed that parental attention was frequently followed by temporary
      decreases in inappropriate mealtime behavior and increases in bite acceptance.
      Moreover, various forms of parental attention resulted in statistically
      significant changes in child behavior, which supports the clinical utility of
      these data.

PMID- 20051525
TI  - An examination of parenting the strong-willed child as bibliotherapy for parents.
AB  - This study examined the Parenting the Strong-Willed Child (PSWC) book as a self
      directed program for parents of 3- to 6-year-olds. Fifty-two parents were
      randomly assigned to PSWC or a comparison book, Touchpoints: Three to Six.
      Assessments occurred at baseline, postintervention (6 weeks after baseline), and
      2-month follow-up. The findings indicated both books, but particularly PSWC, were
      associated with lower levels of child problem behavior after intervention. PSWC
      was associated with greater decreases in child problem behaviors on certain
      measures when amount of reading completed was taken into account. Parents reading
      PSWC reported that they were satisfied with the book and found the book useful
      and easy to implement. The findings are discussed in the contexts of both the
      percentage of parents who read the PSWC book and the cost-effectiveness of a self
      directed intervention.

PMID- 20051528
TI  - Activation of the cardiac mTOR/p70(S6K) pathway by leucine requires PDK1 and
      correlates with PRAS40 phosphorylation.
AB  - Like insulin, leucine stimulates the mammalian target of rapamycin (mTOR)/p70
      ribosomal S6 kinase (p70(S6K)) axis in various organs. Insulin proceeds via the
      canonical association of phosphatidylinositol 3-kinase (PI3K), phosphoinositide
      dependent protein kinase-1 (PDK1), and protein kinase B (PKB/Akt). The signaling
      involved in leucine effect, although known to implicate a PI3K mechanism
      independent of PKB/Akt, is more poorly understood. In this study, we investigated
      whether PDK1 could also participate in the events leading to mTOR/p70(S6K)
      activation in response to leucine in the heart. In wild-type hearts, both leucine
      and insulin increased p70(S6K) activity whereas, in contrast to insulin, leucine
      was unable to activate PKB/Akt. The changes in p70(S6K) activity induced by
      insulin and leucine correlated with changes in phosphorylation of Thr(389), the
      mTOR phosphorylation site on p70(S6K), and of Ser(2448) on mTOR, both related to
      mTOR activity. Leucine also triggered phosphorylation of the proline-rich Akt/PKB
      substrate of 40 kDa (PRAS40), a new pivotal mTOR regulator. In PDK1 knockout
      hearts, leucine, similarly to insulin, failed to induce the phosphorylation of
      mTOR and p70(S6K), leading to the absence of p70(S6K) activation. The loss of
      leucine effect in absence of PDK1 correlated with the lack of PRAS40
      phosphorylation. Moreover, the introduction in PDK1 of the L155E mutation, which
      is known to preserve the insulin-induced and PKB/Akt-dependent phosphorylation of
      mTOR/p70(S6K), suppressed all leucine effects, including phosphorylation of mTOR,
      PRAS40, and p70(S6K). We conclude that the leucine-induced stimulation of the
      cardiac PRAS40/mTOR/p70(S6K) pathway requires PDK1 in a way that differs from
      that of insulin.

PMID- 20051529
TI  - Orexin activation precedes increased NPY expression, hyperphagia, and metabolic
      changes in response to sleep deprivation.
AB  - Several pieces of evidence support that sleep duration plays a role in body
      weight control. Nevertheless, it has been assumed that, after the identification
      of orexins (hypocretins), the molecular basis of the interaction between sleep
      and energy homeostasis has been provided. However, no study has verified the
      relationship between neuropeptide Y (NPY) and orexin changes during hyperphagia
      induced by sleep deprivation. In the current study we aimed to establish the time
      course of changes in metabolite, endocrine, and hypothalamic neuropeptide
      expression of Wistar rats sleep deprived by the platform method for a distinct
      period (from 24 to 96 h) or sleep restricted for 21 days (SR-21d). Despite
      changes in the stress hormones, we found no changes in food intake and body
      weight in the SR-21d group. However, sleep-deprived rats had a 25-35% increase in
      their food intake from 72 h accompanied by slight weight loss. Such changes were
      associated with increased hypothalamus mRNA levels of prepro-orexin (PPO) at 24 h
      followed by NPY at 48 h of sleep deprivation. Conversely, sleep recovery reduced
      the expression of both PPO and NPY, which rapidly brought the animals to a
      hypophagic condition. Our data also support that sleep deprivation rapidly
      increases energy expenditure and therefore leads to a negative energy balance and
      a reduction in liver glycogen and serum triacylglycerol levels despite the
      hyperphagia. Interestingly, such changes were associated with increased serum
      levels of glucagon, corticosterone, and norepinephrine, but no effects on leptin,
      insulin, or ghrelin were observed. In conclusion, orexin activation accounts for
      the myriad changes induced by sleep deprivation, especially the hyperphagia
      induced under stress and a negative energy balance.

PMID- 20051530
TI  - Unfolding the mechanisms of disease progression in permanent neonatal diabetes.

PMID- 20051526
TI  - From estrogen-centric to aging and oxidative stress: a revised perspective of the
      pathogenesis of osteoporosis.
AB  - Estrogen deficiency has been considered the seminal mechanism of osteoporosis in
      both women and men, but epidemiological evidence in humans and recent mechanistic
      studies in rodents indicate that aging and the associated increase in reactive
      oxygen species (ROS) are the proximal culprits. ROS greatly influence the
      generation and survival of osteoclasts, osteoblasts, and osteocytes. Moreover,
      oxidative defense by the FoxO transcription factors is indispensable for skeletal
      homeostasis at any age. Loss of estrogens or androgens decreases defense against
      oxidative stress in bone, and this accounts for the increased bone resorption
      associated with the acute loss of these hormones. ROS-activated FoxOs in early
      mesenchymal progenitors also divert ss-catenin away from Wnt signaling, leading
      to decreased osteoblastogenesis. This latter mechanism may be implicated in the
      pathogenesis of type 1 and 2 diabetes and ROS-mediated adverse effects of
      diabetes on bone formation. Attenuation of Wnt signaling by the activation of
      peroxisome proliferator-activated receptor gamma by ligands generated from lipid
      oxidation also contributes to the age-dependent decrease in bone formation,
      suggesting a mechanistic explanation for the link between atherosclerosis and
      osteoporosis. Additionally, increased glucocorticoid production and sensitivity
      with advancing age decrease skeletal hydration and thereby increase skeletal
      fragility by attenuating the volume of the bone vasculature and interstitial
      fluid. This emerging evidence provides a paradigm shift from the "estrogen
      centric" account of the pathogenesis of involutional osteoporosis to one in which
      age-related mechanisms intrinsic to bone and oxidative stress are protagonists
      and age-related changes in other organs and tissues, such as ovaries, accentuate
      them.

PMID- 20051531
TI  - Human carboxylesterase 1 stereoselectively binds the nerve agent cyclosarin and
      spontaneously hydrolyzes the nerve agent sarin.
AB  - Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases
      and produce a rapid and lethal cholinergic crisis. Development of protein-based
      therapeutics is being pursued with the goal of preventing nerve agent toxicity
      and protecting against the long-term side effects of these agents. The drug
      metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based
      therapeutic because of its similarity in structure and function to the
      cholinesterase targets of nerve agent poisoning. However, the ability of wild
      type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been
      determined. We report the crystal structure of hCE1 in complex with the nerve
      agent cyclosarin. We further use stereoselective nerve agent analogs to establish
      that hCE1 exhibits a 1700- and 2900-fold preference for the P(R) enantiomers of
      analogs of soman and cyclosarin, respectively, and a 5-fold preference for the
      P(S) isomer of a sarin analog. Finally, we show that for enzyme inhibited by
      racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the
      presence of sarin but not soman or cyclosarin. The addition of the neutral oxime
      2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin
      inhibition by more than 60-fold but has no effect on reactivation with the other
      agents examined. Taken together, these data demonstrate that hCE1 is only
      reactivated after inhibition with the more toxic P(S) isomer of sarin. These
      results provide important insights toward the long-term goal of designing novel
      forms of hCE1 to act as protein-based therapeutics for nerve agent
      detoxification.

PMID- 20051532
TI  - Regulation of multidrug resistance protein 1 by tumor necrosis factor alpha in
      cultured glial cells: involvement of nuclear factor-kappaB and c-Jun N-terminal
      kinase signaling pathways.
AB  - Pharmacotherapy of brain HIV-1 infection may be limited by ABC transporters
      [i.e., P-glycoprotein (P-gp), multidrug resistance protein 1 (Mrp1)] that export
      antiretroviral drugs from HIV-1 brain cellular targets (i.e., astrocytes,
      microglia). Using an in vitro astrocyte model of an HIV-1 associated inflammatory
      response, our laboratory has shown that cytokines [i.e., tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6], which are secreted in response
      to HIV-1 envelope glycoprotein gp120 exposure, can decrease P-gp functional
      expression; however, it is unknown whether these same cytokines can alter
      expression and/or activity of other ABC transporters (i.e., Mrp1). In primary
      cultures of rat astrocytes, Mrp1 expression was increased by TNF-alpha (2.7-fold)
      but was not altered by IL-1 beta or IL-6. Cellular retention of 2',7'-bis-(2
      carboxyethyl)-5-(and-6)-carboxyfluorescein, an Mrp substrate, was reduced in TNF
      alpha-treated astrocytes, suggesting increased Mrp-mediated transport.
      Pharmacologic inhibition of nuclear factor-kappaB (NF-kappaB) signaling with SN50
      prevented both TNF-alpha release and Mrp1 expression changes in astrocytes
      triggered with gp120; however, SN50 did not attenuate Mrp1 expression in cells
      triggered with TNF-alpha. In contrast, Mrp1 functional expression was not altered
      in the presence of gp120 or TNF-alpha when astrocyte cultures were pretreated
      with 1,9-pyrazoloanthrone (SP600125), an established c-Jun N-terminal kinase
      (JNK) inhibitor. SP600125 did not affect TNF-alpha release from cultured
      astrocytes triggered with gp120. Mrp1 mRNA expression was increased after
      treatment with gp120 (1.6-fold) or TNF-alpha (1.7-fold), suggesting altered Mrp1
      gene transcription. These data suggest that gp120 and TNF-alpha can up-regulate
      Mrp1 expression in cultured astrocytes. Furthermore, our results imply that both
      NF-kappaB and JNK signaling are involved in Mrp1 regulation during an HIV-1
      associated inflammatory response.

PMID- 20051527
TI  - Molecular aspects of thyroid hormone actions.
AB  - Cellular actions of thyroid hormone may be initiated within the cell nucleus, at
      the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone
      nuclear receptors (TRs) mediate the biological activities of T(3) via
      transcriptional regulation. Two TR genes, alpha and beta, encode four T(3)
      binding receptor isoforms (alpha1, beta1, beta2, and beta3). The transcriptional
      activity of TRs is regulated at multiple levels. Besides being regulated by T(3),
      transcriptional activity is regulated by the type of thyroid hormone response
      elements located on the promoters of T(3) target genes, by the developmental- and
      tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory
      proteins. These nuclear coregulatory proteins modulate the transcription activity
      of TRs in a T(3)-dependent manner. In the absence of T(3), corepressors act to
      repress the basal transcriptional activity, whereas in the presence of T(3),
      coactivators function to activate transcription. The critical role of TRs is
      evident in that mutations of the TRbeta gene cause resistance to thyroid hormones
      to exhibit an array of symptoms due to decreasing the sensitivity of target
      tissues to T(3). Genetically engineered knockin mouse models also reveal that
      mutations of the TRs could lead to other abnormalities beyond resistance to
      thyroid hormones, including thyroid cancer, pituitary tumors, dwarfism, and
      metabolic abnormalities. Thus, the deleterious effects of mutations of TRs are
      more severe than previously envisioned. These genetic-engineered mouse models
      provide valuable tools to ascertain further the molecular actions of unliganded
      TRs in vivo that could underlie the pathogenesis of hypothyroidism. Actions of
      thyroid hormone that are not initiated by liganding of the hormone to
      intranuclear TR are termed nongenomic. They may begin at the plasma membrane or
      in cytoplasm. Plasma membrane-initiated actions begin at a receptor on integrin
      alphavbeta3 that activates ERK1/2 and culminate in local membrane actions on ion
      transport systems, such as the Na(+)/H(+) exchanger, or complex cellular events
      such as cell proliferation. Concentration of the integrin on cells of the
      vasculature and on tumor cells explains recently described proangiogenic effects
      of iodothyronines and proliferative actions of thyroid hormone on certain cancer
      cells, including gliomas. Thus, hormonal events that begin nongenomically result
      in effects in DNA-dependent effects. l-T(4) is an agonist at the plasma membrane
      without conversion to T(3). Tetraiodothyroacetic acid is a T(4) analog that
      inhibits the actions of T(4) and T(3) at the integrin, including angiogenesis and
      tumor cell proliferation. T(3) can activate phosphatidylinositol 3-kinase by a
      mechanism that may be cytoplasmic in origin or may begin at integrin alphavbeta3.
      Downstream consequences of phosphatidylinositol 3-kinase activation by T(3)
      include specific gene transcription and insertion of Na, K-ATPase in the plasma
      membrane and modulation of the activity of the ATPase. Thyroid hormone, chiefly
      T(3) and diiodothyronine, has important effects on mitochondrial energetics and
      on the cytoskeleton. Modulation by the hormone of the basal proton leak in
      mitochondria accounts for heat production caused by iodothyronines and a
      substantial component of cellular oxygen consumption. Thyroid hormone also acts
      on the mitochondrial genome via imported isoforms of nuclear TRs to affect
      several mitochondrial transcription factors. Regulation of actin polymerization
      by T(4) and rT(3), but not T(3), is critical to cell migration. This effect has
      been prominently demonstrated in neurons and glial cells and is important to
      brain development. The actin-related effects in neurons include fostering neurite
      outgrowth. A truncated TRalpha1 isoform that resides in the extranuclear
      compartment mediates the action of thyroid hormone on the cytoskeleton.

PMID- 20051533
TI  - Dominant-negative regulation of cell surface expression by a pentapeptide motif
      at the extreme COOH terminus of an Slo1 calcium-activated potassium channel
      splice variant.
AB  - Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels regulate the physiology
      of many cell types. A single vertebrate gene variously known as Slo1, KCa1.1, or
      KCNMA1 encodes the pore-forming subunits of BK(Ca) channel but is expressed in a
      potentially very large number of alternative splice variants. Two splice variants
      of Slo1, Slo1(VEDEC) and Slo1(QEERL), which differ at the extreme COOH terminus,
      show markedly different steady-state expression levels on the cell surface. Here
      we show that Slo1(VEDEC) and Slo1(QEERL) can reciprocally coimmunoprecipitate,
      indicating that they form heteromeric complexes. Moreover, coexpression of even
      small amounts of Slo1(VEDEC) markedly reduces surface expression of Slo1(QEERL)
      and total Slo1 as indicated by cell-surface biotinylation assays. The effects of
      Slo1(VEDEC) on steady-state surface expression can be attributed primarily to the
      last five residues of the protein based on surface expression of motif-swapped
      constructs of Slo1 in human embryonic kidney (HEK) 293T cells. In addition, the
      presence of the VEDEC motif at the COOH terminus of Slo1 channels is sufficient
      to confer a dominant-negative effect on cell surface expression of itself or
      other types of Slo1 subunits. Treating cells with short peptides containing the
      VEDEC motif increased surface expression of Slo1(VEDEC) channels transiently
      expressed in HEK293T cells and increased current through endogenous BK(Ca)
      channels in mouse podocytes. Slo1(VEDEC) and Slo1(QEERL) channels are removed
      from the HEK293T cell surface with similar kinetics and to a similar extent,
      which suggests that the inhibitory effect of the VEDEC motif is exerted primarily
      on forward trafficking into the plasma membrane.

PMID- 20051534
TI  - Mapping primary care: putting our patients in context.

PMID- 20051535
TI  - Introduction of more editorial board members and google maps and google earth:
      the physician's cheap Geographic Information System (GIS).

PMID- 20051536
TI  - Guest family physician commentaries.

PMID- 20051537
TI  - Geographic Information Systems (GIS): recognizing the importance of place in
      primary care research and practice.

PMID- 20051538
TI  - Using Geographic Information Systems (GIS) to understand a community's primary
      care needs.
AB  - INTRODUCTION: A key element for reducing health care costs and improving
      community health is increased access to primary care and preventative health
      services. Geographic information systems (GIS) have the potential to assess
      patterns of health care utilization and community-level attributes to identify
      geographic regions most in need of primary care access. METHODS: GIS, analytical
      hierarchy process, and multiattribute assessment and evaluation techniques were
      used to examine attributes describing primary care need and identify areas that
      would benefit from increased access to primary care services. Attributes were
      identified by a collaborative partnership working within a practice-based
      research network using tenets of community-based participatory research. Maps
      were created based on socioeconomic status, population density, insurance status,
      and emergency department and primary care safety-net utilization. RESULTS:
      Individual and composite maps identified areas in our community with the greatest
      need for increased access to primary care services. CONCLUSIONS: Applying GIS to
      commonly available community- and patient-level data can rapidly identify areas
      most in need of increased access to primary care services. We have termed this a
      Multiple Attribute Primary Care Targeting Strategy. This model can be used to
      plan health services delivery as well as to target and evaluate interventions
      designed to improve health care access.

PMID- 20051539
TI  - Harnessing Geographic Information Systems (GIS) to enable community-oriented
      primary care.
AB  - BACKGROUND: Despite growing acceptance and implementation of geographic
      information systems (GIS) in the public health arena, its utility for clinical
      population management and coordination by leaders in a primary care clinical
      health setting has been neither fully realized nor evaluated. METHODS: In a
      primary care network of clinics charged with caring for vulnerable urban
      communities, we used GIS to (1) integrate and analyze clinical (practice
      management) data and population (census) data and (2) generate distribution,
      service area, and population penetration maps of those clinics. We then conducted
      qualitative evaluation of the responses of primary care clinic leaders,
      administrators, and community board members to analytic mapping of their clinic
      and regional population data. RESULTS: Practice management data were extracted,
      geocoded, and mapped to reveal variation between actual clinical service areas
      and the medically underserved areas for which these clinics received funding,
      which was surprising to center leaders. In addition, population penetration
      analyses were performed to depict patterns of utilization. Qualitative
      assessments of staff response to the process of mapping clinical and population
      data revealed enthusiastic engagement in the process, which led to enhanced
      community comprehension, new ideas about data use, and an array of applications
      to improve their clinical revenue. However, they also revealed barriers to
      further adoption, including time, expense, and technical expertise, which could
      limit the use of GIS and mapping unless economies of scale across clinics, the
      use of web technology, and the availability of dynamic mapping tools could be
      realized. CONCLUSIONS: Analytic mapping was enthusiastically received and
      practically applied in the primary care setting, and was readily comprehended by
      clinic leaders for innovative purposes. This is a tool of particular relevance
      amid primary care safety-net expansion and increased funding of health
      information technology diffusion in these settings, particularly if the hurdles
      of cost and technological expertise are overcome by harnessing new advances in
      web-based mapping technology.

PMID- 20051540
TI  - Observing the spread of common illnesses through a community: using Geographic
      Information Systems (GIS) for surveillance.
AB  - BACKGROUND: The recent implementation of electronic medical record systems allows
      for the development of systems to track common illness across a defined
      community. With the threats of bioterrorism and pandemic illness, syndromic
      surveillance methodologies have become an important area of study. There has been
      limited study of the application of syndromic surveillance techniques to
      communities for tracking common illnesses to improve health system resource
      allocation and inform communities. METHODS: We analyzed visits from 26 primary
      care sites and one emergency department in a health system during a 13-month
      period in 2007 to 2008. Visits were coded for common respiratory and
      gastrointestinal illnesses. Using geographic information systems techniques, we
      plotted home addresses and developed criteria for census tract inclusion. The
      spatial distribution of the illnesses patterns was analyzed using Bayesian
      smoothing, Kriging and SaTScan (SaTScan, Boston, MA) statistical methods.
      RESULTS: The study included 857,555 visits, 107,286 of which were in the
      emergency department and 750,269 in the primary care sites. Patient visits were
      plotted and then aggregated to census tracts. We determined that at least a
      median of 10 visits per week was required to provide sufficient volume in
      defining census tracts included in the study (109 census tracts). Weekly visit
      rates by census tract were plotted using nearest neighbor empirical Bayesian
      smoothing and Kriging to produce a continuous surface. To detect statistical
      clustering of weekly visit rates, we used SaTScan and identified 7 weeks with
      statistically significant clusters for respiratory illnesses and 8 weeks with
      statistically significant clusters for gastrointestinal illnesses (out of 56
      weeks included in the study). After adjusting for population density, the visit
      rate remained consistent for respiratory illnesses (analysis of variance P =
      .937), but the visit rate for gastrointestinal illnesses increased in the fourth
      population density quartile (statistically different from quartiles 1, 2 and 3;
      analysis of variance P < .001 with Tukey multiple comparisons test), which
      included the highest population density areas in the study. CONCLUSIONS: We were
      able to use geographic information systems to assess visit rates for common
      illnesses in a defined community and identified spatial variability over time.
      Additional research is needed to help define parameters for implementation, but
      we believe this can have benefit for allocation of health resources and
      communicating with the community.

PMID- 20051541
TI  - Sociodemographic characteristics of communities served by retail clinics.
AB  - PURPOSE: As a rapidly growing new health care delivery model in the United
      States, retail clinics have been the subject of much debate and controversy.
      Located physically within a retail store, retail clinics provide simple acute and
      preventive services for a fixed price and without an appointment. Some hope that
      retail clinics can be a new safety-net provider for the poor and those without a
      primary care physician. To better understand the potential for retail clinics to
      achieve this goal, we describe the sociodemographic characteristics of the
      communities in which they operate. METHODS: We created an inventory of all retail
      clinics in the United States and determined the proportion that are in a health
      professional shortage area (HPSA). We defined each retail clinic's catchment area
      as all census blocks that were less than a 5-minute driving distance from the
      clinic. We compared the sociodemographic characteristics of the population within
      and outside of these retail clinic catchment areas. RESULTS: Of the 982 clinics
      in 32 states, 88.4% were in an urban area and 12.5% were in an HPSA (20.9% of the
      US population lives within an HPSA). Compared with the rest of the urban
      population, the population living within a retail clinic catchment area has a
      higher median household income ($52,849 vs $46,080), is better educated (32.6% vs
      24.9% with a college degree), and is as likely to be uninsured (17.7% vs 17.0%).
      In a multivariate model, the census block's median household income had the
      strongest association with whether the census block was in a retail clinic
      catchment area (odds ratio, 3.63; 95% CI, 3.26-4.05; median income, > or =$54,779
      vs <$30,781, respectively). CONCLUSIONS: We found that relatively few retail
      clinics are located in HPSAs and that, compared with the rest of the urban
      population, the population living in close proximity to a retail clinic has a
      higher income.

PMID- 20051542
TI  - American Board of Family Medicine (ABFM) maintenance of certification: variations
      in self-assessment modules uptake within the 2006 cohort.
AB  - INTRODUCTION: In its recent shift to a Maintenance of Certification for Family
      Physicians (MC-FP) paradigm, the American Board of Family Medicine provides
      diplomates completing 3 self-assessment modules (SAMs) in the first 3 years (or
      first stage of MC-FP) a pathway to extend their recertification cycle to 10 years
      provided additional requirements are met, versus a 7-year cycle for "non
      completers." We use geographic information systems to report on variations in SAM
      participation and completion in a single cohort of diplomates followed during
      their first stage of MC-FP to better understand the communities impacted,
      barriers to uptake, and urban-rural differences. METHODS: We merged data from
      2006 MC-FP files, association workforce files, and the US Census and completed
      cross-sectional spatial, descriptive, and regression analyses of the uptake and
      timely completion of SAMs during a 3-year period. Specifically, we explored
      characteristics of diplomates who did not meet first-stage MC-FP requirements
      within 3 years versus those who did. RESULTS: The cohort comprised 10,812
      participants who passed their certification or recertification examination in
      2005, of which 30.5% did not complete their MC-FP requirements by the end of
      2008. Noncompleters were more likely to be older (P < .01), men (P < .0001), and
      from areas of dense poverty (P < .01) and underserved areas (P < .05). There were
      no significant differences in MC-FP completion across the rural-urban continuum
      (P = .7108). CONCLUSIONS: More than two-thirds of eligible, certified family
      physicians completed stage-one MC-FP requirements. Concerns that technical
      aspects of the new MC-FP paradigm would leave parts of a widely distributed,
      poorly resourced primary care workforce disadvantaged may hold true for providers
      in some underserved areas, but differential completion among rural and remote
      physicians was not found. Understanding barriers to uptake is essential if the
      specialty boards are to meet their obligations to the public to promote quality
      of care through Maintenance of Certification for all physicians.

PMID- 20051543
TI  - Incorporating Geographic Information Systems (GIS) into program evaluation:
      lessons from a rural medicine initiative.
AB  - PURPOSE: To address the shortage of physicians practicing in rural areas of
      Michigan, the Wayne State University School of Medicine developed an integrated
      rural core curriculum to interest students in rural practice careers. Here we
      focus on the evaluation strategy used to determine the extent to which students
      in the new rural medicine interest group who self-identified as selecting a rural
      clerkship or externship did secure a clinical training experience in a rural
      setting. METHODS: Three measures of rurality were compared to determine whether
      students were placed in rural training settings: (1) the percentage of the county
      living in rural areas; (2) a county-level dichotomous measure of rural/nonrural;
      and (3) a dichotomous measure based on urban area boundaries within the county.
      Practice address and geographic data were integrated into geographic information
      systems software, which we used to map out rural characteristics of Michigan
      counties through a process called thematic mapping; this shows characteristic
      variation by color-shading geographic features. In addition, reference maps were
      created showing the boundaries of urban areas and metropolitan/micropolitan
      areas. Once these processes were completed, we overlaid the practice location on
      the contextual-level geographic features to produce a visual representation of
      the relationship between student placement and rural areas throughout the state.
      RESULTS: The outcome of student placement in rural practices varied by the
      definition of rural. We concluded that, although students were not placed in the
      most rural areas of Michigan, they received clerkship or externship training near
      rural areas or in semirural areas. CONCLUSION: This process evaluation had a
      direct impact on program management by highlighting gaps in preceptor
      recruitment. A greater effort is being made to recruit physicians for more rural
      areas of the state rather than urban and semirural areas. Geographic information
      systems mapping also defined levels of ruralism for students to help them make
      informed selections of training sties. This is especially important for students
      who are not sure about a rural experience and might be discouraged by placement
      in a remote rural area.

PMID- 20051544
TI  - The relationship between a statewide preceptorship program and family medicine
      residency selection.
AB  - OBJECTIVE: The purpose of this study was to investigate the extent to which
      participation in the California Academy of Family Physicians Foundation Family
      Medicine (FM) Preceptorship Program, as well as medical school, degree earned,
      gender, and match year predicted FM residency match. METHODS: Allopathic and
      osteopathic students who applied to the preceptorship program from 1996 to 2002
      were followed until residency match. Chi-square (chi(2)) analysis was used to
      compare preceptorship participants, nonparticipants (students who applied but did
      not complete the preceptorship), and nonapplicants (students who did not apply to
      the preceptorship) for FM match rates and to compare participants to
      nonparticipants for primary care match rates. FM match data for California
      schools from 1999 to 2005 were used to perform a logistic regression predicting
      FM match. RESULTS: Twenty-four percent of participants matched into FM residency
      programs whereas only 13% of nonparticipants and 13% of nonapplicants selected FM
      (chi(2) = 24.97; P < .001). There was not a statistically significant difference
      between the proportion of participants and nonparticipants who matched into
      primary care (chi(2) = 0.12; P = .73). Odds ratio results of logistic regression
      for participants compared with nonapplicants matching into FM was 2.7 (95% CI,
      2.0-3.6; P < .001). CONCLUSION: Preceptorship program participants were more
      likely than both nonparticipants and nonapplicants to select a FM residency.

PMID- 20051545
TI  - Having a personal healthcare provider and receipt of adequate cervical and breast
      cancer screening.
AB  - INTRODUCTION: The purpose of this study was to assess the relationship between
      having a personal health care provider and adequate cervical and breast cancer
      screening behavior. METHODS: Cross-sectional data were obtained from the 2004
      Behavior Risk Factor Surveillance System. For cervical cancer, female respondents
      18 years of age and older who did not have hysterectomy were included (n =
      130,359); for breast cancer, female respondents 40 years of age or older were
      included (n = 129,929). Multiple logistic regression analyses were performed to
      determine the association between having a personal health care provider,
      specific demographics, and health insurance status with adequate cervical and
      breast cancer screening behavior. RESULTS: Approximately 9% and 14% of the study
      population for the breast cancer and cervical cancer analyses, respectively, did
      not have a personal health care provider. Having at least one personal health
      care provider was significantly associated with adequate cervical cancer
      screening behavior (odds ratio, 2.37; 95% CI, 2.08-2.70) and breast cancer
      screening behavior (odds ratio, 2.86; 95% CI, 2.54-3.24) in multivariate
      analyses. Both multivariate analyses were adjusted for age, race/ethnicity,
      education, income, and health insurance. CONCLUSION: Having at least one personal
      health care provider was associated with adequate cervical and breast cancer
      screening behavior. Efforts to increase primary care access are a necessary part
      of the plan to increase preventive health services utilization.

PMID- 20051546
TI  - Does having a personal physician improve quality of care in diabetes?
AB  - PURPOSE: Although having a continuous relationship with a physician is a defining
      feature of primary care, few studies have evaluated the effect of this on chronic
      disease management. This aim of this study was to examine whether having a
      regular physician is associated with improvements in reaching treatment goals for
      patients with diabetes. METHODS: Through the use of a diabetes registry, patients
      diagnosed with diabetes mellitus for a minimum of 6 months cared for in a large,
      single academic family medicine practice were compared based on whether they had
      a regular physician or not. The 2 groups were compared in the frequency in which
      they achieved goals for management of glycated hemoglobin, blood pressure, low
      density lipoprotein cholesterol, and other aspects of diabetes care. RESULTS:
      Patients with a regular provider were slightly older than those without a
      provider (57.5 years vs. 50.9 years; P = .002), but the gender distribution and
      percent who were smokers was the same. In assessing diabetes quality measures,
      patients with a regular provider had lower average levels of glycated hemoglobin
      (7.70 vs 8.53; P = .01), but no difference was noted in the percentage achieving
      a goal of < or =7.0. No differences were noted between the groups in either the
      average systolic or diastolic blood pressures or low-density lipoprotein
      cholesterol or in the percentages of patients achieving recognized goals for
      these measures. When examining other preventive services, patients with a regular
      provider were more likely to receive an influenza immunization within the last
      year (51.8% vs 35.6%; P = .02) but no more likely to receive a pneumococcal
      vaccine or take an aspirin each day. CONCLUSION: This study suggests that there
      are few benefits for patients with diabetes in having an established regular
      provider over having a regular place of service.

PMID- 20051547
TI  - Using Geographic Information Systems (GIS) to assess outcome disparities in
      patients with type 2 diabetes and hyperlipidemia.
AB  - OBJECTIVES: Geographic information systems (GIS) tools can help expand our
      understanding of disparities in health outcomes within a community. The purpose
      of this project was (1) to demonstrate the methods to link a disease management
      registry with a GIS mapping and analysis program, (2) to address the challenges
      that occur when performing this link, and (3) to analyze the outcome disparities
      resulting from this assessment tool in a population of patients with type 2
      diabetes mellitus. METHODS: We used registry data derived from the University of
      California Davis Health System's electronic medical record system to identify
      patients with diabetes mellitus from a network of 13 primary care clinics in the
      greater Sacramento area. This information was converted to a database file for
      use in the GIS software. Geocoding was performed and after excluding those who
      had unknown home addresses we matched 8528 unique patient records with their
      respective home addresses. Socioeconomic and demographic data were obtained from
      the Geolytics, Inc. (East Brunswick, NJ), a provider of US Census Bureau data,
      with 2008 estimates and projections. Patient, socioeconomic, and demographic data
      were then joined to a single database. We conducted regression analysis assessing
      A1c level based on each patient's demographic and laboratory characteristics and
      their neighborhood characteristics (socioeconomic status [SES] quintile). Similar
      analysis was done for low-density lipoprotein cholesterol. RESULTS: After
      excluding ineligible patients, the data from 7288 patients were analyzed. The
      most notable findings were as follows: There was, there was found an association
      between neighborhood SES and A1c. SES was not associated with low-density
      lipoprotein control. CONCLUSION: GIS methodology can assist primary care
      physicians and provide guidance for disease management programs. It can also help
      health systems in their mission to improve the health of a community. Our
      analysis found that neighborhood SES was a barrier to optimal glucose control but
      not to lipid control. This research provides an example of a useful application
      of GIS analyses applied to large data sets now available in electronic medical
      records.

PMID- 20051548
TI  - The prognostic implications of night sweats in two cohorts of older patients.
AB  - BACKGROUND: When asked, a significant number of patients report having
      experienced night sweats. Those who do are more likely to report decreased
      physical health, mental health, and quality of life. In most cases the cause of
      night sweats is unknown. We therefore do not know how much to worry about
      patients with this symptom. The present study examined associations between night
      sweats and mortality. METHODS: We used logistic regression and proportional
      hazards analyses to investigate potential predictors of mortality, including
      night sweats reported at baseline, among 2 different cohorts of people older than
      65 years of age (n = 682 and n = 852) who were followed for an average of 7.3 and
      7.5 years, respectively. RESULTS: Patients who reported night sweats were not
      more likely to die or to die sooner than those who did not report night sweats
      after controlling for age, sex, body mass index, education, and income. This held
      true as well for patients who reported more severe night sweats among the cohort
      in which the severity of night sweats was quantified. CONCLUSIONS: Patients who
      report night sweats on a primary care health history questionnaire do not seem,
      on average, to be at increased risk for mortality.

PMID- 20051549
TI  - Physician supply and breast cancer survival.
AB  - BACKGROUND: This study tested the hypothesis that physician supply thresholds are
      associated with breast cancer survival in Ontario. METHODS: The 5-year survival
      of 17,820 female breast cancer patients diagnosed between 1995 and 1997 was
      surveilled until 2003 for all-cause mortality. Physician supply densities in 1991
      and 2001 were computed for 49 Ontario regions. RESULTS: There were independent
      threshold effects for general practitioners (GP; 7.25 per 10,000) and
      obstetrician/gynecologists (OB/GYN; 6 per 100,000) at or above which women with
      breast cancer were more likely to survive for 5 years. The respective risk of
      living in areas undersupplied with OB/GYN and GP increased 30% to nearly 5-fold
      during the 1990s. Five-year survival tended to be lower in provincial areas
      outside of Toronto, which experienced GP (odds ratio, 0.83; 90% CI, 0.70-0.99)
      and OB/GYN (odds ratio, 0.76; 95% CI, 0.61-0.96) supply decreases. CONCLUSION: As
      they do in America, primary care physician supplies in Canada seem to matter in
      the effective provision of cancer care. Community resources such as health care
      service endowments, including physician supplies, may be particularly critical to
      the performance of health care systems such as Canada's, which aim to provide
      medically necessary care for all.

PMID- 20051550
TI  - Geographic Information Systems (GIS) demonstrating primary care needs for a
      transitioning hispanic community.
AB  - BACKGROUND: Hispanics are the largest and fastest growing minority group in the
      United States. Charlotte, NC, had the 4th fastest growing Hispanic community in
      the nation between 1990 to 2000. Gaining understanding of the patterns of health
      care use for this changing population is a key step toward designing improved
      primary care access and community health. METHODS: The Multiple Attribute Primary
      Care Targeting Strategy process was applied to key patient- and community-level
      attributes describing the Charlotte Hispanic community. Maps were created based
      on socioeconomic status, population density, insurance status, and use of the
      emergency department as a primary care safety net. Each of these variables was
      weighed and added to create a single composite map. RESULTS: Individual attribute
      maps and the composite map identified geographic locations where Hispanic
      community members would most benefit from increased access to primary care
      services. CONCLUSIONS: Using the Multiple Attribute Primary Care Targeting
      Strategy process we were able to identify geographic areas within our community
      where many Hispanic immigrants face barriers to accessing appropriate primary
      care services. These areas can subsequently be targeted for interventions that
      improve access to primary care and reduce emergency department use. The
      geospatial model created through this process can be monitored over time to
      determine the effectiveness of these interventions.

PMID- 20051551
TI  - Bandaging society's wounds: a primary care perspective.
AB  - Our patients often carry heavy burdens into the examination room. With our
      standard questioning, we medically divide and define them into recognizable
      parts, but as pieces of a whole they resist healing. Can we regain a vision of
      health beyond the isolated individual to one who might belong to a larger
      community of concern?

PMID- 20051552
TI  - Ischemic colitis related to sumatriptan overuse.
AB  - BACKGROUND: Serotonin-1 5-hydroxytryptamine (5-HT 1) receptor agonists are first
      line agents for migraine headaches. Patients with refractory headaches may use
      supratherapeutic doses of these medications. Described is a case of ischemic
      colitis related to overuse of sumatriptan. CASE: A 35-year-old woman presented
      with severe abdominal pain without diarrhea or hematochezia. For several days
      prior she had been self-treating a refractory migraine headache with frequent
      doses of sumatriptan. She is a nonsmoker and took no oral contraceptives or other
      serotonin agonists. A computed tomography scan of the abdomen revealed left-sided
      colitis. A colonoscopy with biopsy confirmed ischemic colitis and excluded
      inflammatory bowel disease (IBD). DISCUSSION: Previously published case reports
      have suggested an association between 5-HT 1 receptor agonists and ischemic
      colitis. These reports have been dismissed because the patients were taking oral
      contraceptives, serotonin agonists, or had other comorbidities. This healthy
      patient lacked risk factors for ischemia, is the youngest to be reported, and is
      the first without hematochezia. CONCLUSION: 5-HT 1 receptor agonists are
      generally considered safe. Ischemic colitis is a potentially serious complication
      of these agents. A retrospective review of 5-HT 1 receptor agonist users who have
      presented with acute onset abdominal pain or hematochezia is necessary to
      elucidate the incidence of this adverse event.

PMID- 20051553
TI  - The impact of a clinic move on vulnerable patients with chronic disease: a
      Geographic Information Systems (GIS) analysis.
AB  - BACKGROUND: Changing locations disrupts the populations served by primary health
      care clinics, and such changes may differentially affect access to care for
      vulnerable populations. METHODS: Online geographic information systems mapping
      tools were used to define how the relocation of a family medicine center impacted
      access to care for black and Hispanic patients with chronic disease. RESULTS:
      Maps created from practice management data revealed a distinct shift in black and
      Hispanic patients with chronic disease being served in the new location.
      CONCLUSIONS: Geographic information systems tools are valuable aids in defining
      changing service areas of primary health care clinics.

PMID- 20051554
TI  - Re: interventions to improving osteoporosis screening: an Iowa Research Network
      (IRENE) study.

PMID- 20051555
TI  - Re: interventions to improving osteoporosis screening: an Iowa Research Network
      (IRENE) study.

PMID- 20051556
TI  - Cross-mapping and the identification of editing sites in mature microRNAs in high
      throughput sequencing libraries.
AB  - MicroRNAs (miRNAs) are short (20-23 nt) RNAs that are sequence-specific mediators
      of transcriptional and post-transcriptional regulation of gene expression. Modern
      high-throughput technologies enable deep sequencing of such RNA species on an
      unprecedented scale. We find that the analysis of small RNA deep-sequencing
      libraries can be affected by cross-mapping, in which RNA sequences originating
      from one locus are inadvertently mapped to another. Similar to cross
      hybridization on microarrays, cross-mapping is prevalent among miRNAs, as they
      tend to occur in families, are similar or derived from repeat or structural RNAs,
      or are post-transcriptionally modified. Here, we develop a strategy to correct
      for cross-mapping, and apply it to the analysis of RNA editing in mature miRNAs.
      In contrast to previous reports, our analysis suggests that RNA editing in mature
      miRNAs is rare in animals.

PMID- 20051557
TI  - Experiences of sexual harassment among elementary school students in Taiwan:
      implications for school nurses.
AB  - Sexual harassment is a significant issue in the lives of students. Understanding
      how young adolescents feel about sexual harassment and their coping strategies is
      a central element to guide school nursing interventions promoting sexual health.
      This study explored the sexual harassment experiences of young adolescents in
      Taiwan. A qualitative research design was employed using focus groups to collect
      data from 47 elementary students, 10 and 12 years of age. Three themes emerged
      from the data analysis: "experiences of physical harassment," "experiences of
      verbal harassment," and "coping with harassment." The potential for school nurses
      to influence students' behavior, improve sexual health instruction, and create a
      healthy school environment is significant. School nurses should participate in
      sexual health education classes actively to advance the sexual health behaviors
      of school children.

PMID- 20051558
TI  - An 86-year-old woman with cardiac cachexia contemplating the end of her life:
      review of hospice care.
AB  - Mrs H is an 86-year-old woman with progressive congestive heart failure and
      multiple chronic conditions who is experiencing worsening function and quality of
      life despite maximum medical therapies. She seeks advice regarding control over
      the circumstances of the end of her life, be it by suicide or under hospice care.
      Typical of US populations older than 65 years with multiple chronic health
      conditions and functional decline who are facing the end of life, Mrs H's
      concerns are particularly about quality of life, not being a burden on loved
      ones, and maintaining control. As she demonstrates, psychological, existential,
      and social factors, particularly fear of being a burden, are more common reasons
      for desiring hastened death than those related directly to physical symptoms.
      Hospice, which provides a multidisciplinary approach to care at the end of life,
      can assist Mrs H and her family in making decisions that are consistent with her
      goals.

PMID- 20051559
TI  - The cover. Study for Phidias in the Apotheosis of Homer.

PMID- 20051560
TI  - A piece of my mind. Integration.

PMID- 20051561
TI  - Researchers hope measuring performance will improve stroke care and prevention.

PMID- 20051562
TI  - Scientists probe brain's role in obesity.

PMID- 20051564
TI  - Hormonal therapy for prostate cancer in men with heart disease.

PMID- 20051565
TI  - Hormonal therapy for prostate cancer in men with heart disease.

PMID- 20051566
TI  - Age and prostate cancer survival.

PMID- 20051567
TI  - Typhoid fever in the United States and antibiotic choice.

PMID- 20051568
TI  - Process measures, outcome measures, and heart failure.

PMID- 20051570
TI  - Update: A 39-year-old man with a skin infection.

PMID- 20051569
TI  - Antidepressant drug effects and depression severity: a patient-level meta
      analysis.
AB  - CONTEXT: Antidepressant medications represent the best established treatment for
      major depressive disorder, but there is little evidence that they have a specific
      pharmacological effect relative to pill placebo for patients with less severe
      depression. OBJECTIVE: To estimate the relative benefit of medication vs placebo
      across a wide range of initial symptom severity in patients diagnosed with
      depression. DATA SOURCES: PubMed, PsycINFO, and the Cochrane Library databases
      were searched from January 1980 through March 2009, along with references from
      meta-analyses and reviews. STUDY SELECTION: Randomized placebo-controlled trials
      of antidepressants approved by the Food and Drug Administration in the treatment
      of major or minor depressive disorder were selected. Studies were included if
      their authors provided the requisite original data, they comprised adult
      outpatients, they included a medication vs placebo comparison for at least 6
      weeks, they did not exclude patients on the basis of a placebo washout period,
      and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies
      (718 patients) were included. DATA EXTRACTION: Individual patient-level data were
      obtained from study authors. RESULTS: Medication vs placebo differences varied
      substantially as a function of baseline severity. Among patients with HDRS scores
      below 23, Cohen d effect sizes for the difference between medication and placebo
      were estimated to be less than 0.20 (a standard definition of a small effect).
      Estimates of the magnitude of the superiority of medication over placebo
      increased with increases in baseline depression severity and crossed the
      threshold defined by the National Institute for Clinical Excellence for a
      clinically significant difference at a baseline HDRS score of 25. CONCLUSIONS:
      The magnitude of benefit of antidepressant medication compared with placebo
      increases with severity of depression symptoms and may be minimal or nonexistent,
      on average, in patients with mild or moderate symptoms. For patients with very
      severe depression, the benefit of medications over placebo is substantial.

PMID- 20051571
TI  - Extra calories cause weight gain--but how much?

PMID- 20051572
TI  - Health and safety risks of carbon capture and storage.

PMID- 20051573
TI  - Cap and trade legislation for greenhouse gas emissions: public health benefits
      from air pollution mitigation.

PMID- 20051574
TI  - Diagnosis and management of lumbar spinal stenosis.

PMID- 20051575
TI  - JAMA patient page. Acute coronary syndromes.

PMID- 20051576
TI  - The academic and functional academic skills of youth who are at risk for language
      impairment in residential care.
AB  - PURPOSE: Undiagnosed language impairment (LI) for youth in residential care is a
      concern as similar populations have shown elevated levels of language delays.
      Therefore, the purposes of this study were to identify the percentage of youth in
      residential care who are at risk for LI and to compare the demographic, academic
      achievement, and functional academic skills of youth with or without possible LI.
      METHOD: Participants were 80 youth in residential care. Risk for LI was
      determined using the Clinical Evaluation of Language Fundamentals-4 Screening
      Test (E. Semel, E. H. Wiig, & W. A. Secord, 2004). Independent-samples t tests
      and chi-square analyses were conducted to assess the differences between groups.
      Measures used included the Woodcock-Johnson Test of Achievement (R. W. Woodcock,
      K. S. McGrew, & N. Mather, 2001) and the Kaufman Functional Academic Skills Test
      (A. S. Kaufman & N. L. Kaufman, 1994). RESULTS: More than half of the sample
      (54%) were identified as being at risk for LI. Statistically significant
      differences between youth with and without LI were found on academic variables.
      Specifically, youth who were at risk for LI presented academic achievement and
      functional academic scores in the low to low-average ranges. CONCLUSION: Findings
      suggest that there is a need to screen youth entering residential programs for
      possible LI. Implications for treatment and program planning are discussed.

PMID- 20051577
TI  - A review of developmental and applied language research on African American
      children: from a deficit to difference perspective on dialect differences.
AB  - PURPOSE: The contemporary practices of delivering speech, language, and hearing
      services in schools reflect palpable gains in professional sensitivity to
      linguistic and cultural diversity. METHOD: This article reviews the dominant
      research themes on the oral language of African American preschoolers who
      contribute to such diversity in the United States. Specifically, it contrasts the
      historical and current frameworks that have guided studies of (a) such children's
      acquisition and use of English and (b) the strategies used to assess and modify
      their language. CONCLUSION: Research initiatives that can expand knowledge about
      this group are proposed.

PMID- 20051578
TI  - Data recycling: using existing databases to increase research capacity in speech
      language development and disorders.
AB  - PURPOSE: This clinical forum was organized to provide a means for informing the
      research and clinical communities of one mechanism through which research
      capacity might be enhanced within the field of speech-language pathology.
      Specifically, forum authors describe the process of conducting secondary analyses
      of extant databases to answer questions of relevance to speech and language
      development and disorders. METHOD: This prologue defines the concept of secondary
      analysis of databases and provides an overview of each of the articles that make
      up the forum. CONCLUSION: Researchers invested in addressing basic and applied
      problems of relevance to speech and language services in schools can make use of
      a variety of extant databases to increase research capacity.

PMID- 20051579
TI  - Advancing research on children with speech-language impairment: an introduction
      to the Early Childhood Longitudinal Study--Kindergarten Cohort.
AB  - PURPOSE: The Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K; U.S.
      Department of Education, 2000) includes comprehensive assessments of home,
      classroom, and school contexts and developmental outcomes for a nationally
      representative sample of more than 20,000 children who began kindergarten in 1998
      1999. The purposes of this article are to describe the ECLS-K and provide an
      example of how to use these data to advance speech-language-hearing research.
      METHOD: Special education questionnaires were analyzed from subsamples of
      children with diagnosed disabilities. The frequencies of different disabilities
      at kindergarten, 1st, 3rd, and 5th grade were calculated, and for children whose
      primary diagnosis was speech-language impairment, special education experiences
      were summarized. RESULTS: There are relatively large subsamples of children with
      learning disabilities, physical disabilities, and speech-language impairments.
      Among children with speech-language impairments, there is substantial variability
      in special education experiences with regard to the amount of time children
      received services, location of services, types of instructional methods, and
      extent to which modifications were made to the general education curriculum.
      CONCLUSION: The comprehensive assessments, large subsamples of children with
      diagnosed disabilities, and detailed information about special education services
      makes the ECLS-K a useful resource for advancing the development of theory,
      effective classroom practices, and evidence-based policies that promote the well
      being of children with special needs.

PMID- 20051580
TI  - Using language sample databases.
AB  - PURPOSE: Over the past 50 years, language sample analysis (LSA) has evolved from
      a powerful research tool that is used to document children's linguistic
      development into a powerful clinical tool that is used to identify and describe
      the language skills of children with language impairment. The The Systematic
      Analysis of Language Transcripts (SALT; J. F. Miller & A. Iglesias, 2008)
      Software Project has developed several databases of language samples from more
      than 6,000 typical speakers. This article presents an overview of the SALT
      databases and then demonstrates the power of these databases in classifying
      children with language impairment. METHOD: Conversational language samples were
      elicited from 244 children with language impairment who were between 3 and 13
      years of age. Language production measures generated from these transcripts were
      compared to measures from 244 transcripts in the SALT conversational database. A
      series of discriminant function analyses were completed to document the
      sensitivity and specificity of the language sample measures. RESULTS: The
      language sample measures were effective in classifying children based on their
      language status, with correct identification of 78% of the children with language
      impairment and 85% of the children who were typically developing. CONCLUSION: The
      SALT databases provide a useful tool for the clinical management of children with
      language impairment.

PMID- 20051581
TI  - Home literacy experiences and early childhood disability: a descriptive study
      using the National Household Education Surveys (NHES) program database.
AB  - PURPOSE: The present article illustrates how the National Household Education
      Surveys (NHES; U.S. Department of Education, 2009) database might be used to
      address questions of relevance to researchers who are concerned with literacy
      development among young children. Following a general description of the NHES
      database, a study is provided that examines the extent to which parent-reported
      home literacy activities and child emergent literacy skills differ for children
      with (a) developmental disabilities versus those who are developing typically,
      (b) single disability versus multiple disabilities, and (c) speech-language
      disability only versus other types of disabilities. METHOD: Four hundred and
      seventy-eight preschool-age children with disabilities and a typically developing
      matched sample (based on parent report) were identified in the 2005
      administration of the Early Childhood Program Participation (ECPP) Survey in the
      NHES database. Parent responses to survey items were then compared between
      groups. RESULTS: After controlling for age and socioeconomic status, no
      significant differences were found in the frequency of home literacy activities
      for children with and without disabilities. Parents reported higher levels of
      emergent literacy skills for typically developing children relative to children
      with disabilities. CONCLUSIONS: These findings suggest the importance of
      considering the home literacy experiences and emergent literacy skills of young
      children with disabilities when making clinical recommendations.

PMID- 20051582
TI  - The EpiSLI database: a publicly available database on speech and language.
AB  - PURPOSE: This article describes a database that was created in the process of
      conducting a large-scale epidemiologic study of specific language impairment
      (SLI). As such, this database will be referred to as the EpiSLI database.
      Children with SLI have unexpected and unexplained difficulties learning and using
      spoken language. Although there is no uniform standard for the diagnosis of SLI,
      the construct encompasses a language deficit occurring in the presence of grossly
      normal sensory and nonverbal cognitive abilities (H. Tager-Flusberg & J. Cooper,
      1999). Although these language difficulties are most apparent during the
      preschool and early school years, evidence now exists that these problems are
      usually present well into adulthood and are probably present throughout a
      person's life (see, for instance, C. J. Johnson et al., 1999; S. E. Stothard, M.
      J. Snowling, D. V. M. Bishop, B. B. Chipchase, & C. A. Kaplan, 1998; J. B.
      Tomblin, 2008). DISCUSSION: Much of what we know of these children has come from
      research on children who have been clinically identified and served. Certainly,
      by studying those who are being served, our research base is most likely to be
      relevant to clinical services. However, there is a danger in this research
      strategy. It is quite possible that not all children with SLI are clinically
      identified and served within our service delivery systems. In such circumstances,
      there is the potential for systematic factors to influence which children do or
      do not find their way to clinical service. CLINICAL IMPLICATIONS: If our research
      questions are concerned with the characteristics of the actual population of
      children with SLI that exists in our communities and not just those who are being
      served, then we need to turn to methods of epidemiology to aid our research.

PMID- 20051587
TI  - Comparative pharmacokinetics of a once-daily tramadol extended-release tablet and
      an immediate-release reference product following single-dose and multiple-dose
      administration.
AB  - The pharmacokinetics of a once-daily formulation of tramadol (Tramadol Contramid
      OAD 200-mg tablets) following single-dose and multiple-dose administration was
      compared with that of an immediate-release product (tramadol IR 50-mg tablets) in
      2 separate studies. In both studies, AUC parameters met bioequivalence criteria,
      whereas C(max) of Tramadol Contramid OAD was lower than that of tramadol IR
      following a 200-mg daily dosage. After single-dose administration, the mean
      tramadol concentration at 1 hour postdose was within the range associated with
      analgesic efficacy (>100 ng/mL), and the mean concentration remained above this
      level for the remainder of the dosing interval. Steady state was attained within
      48 hours following multiple-dose administration. Tramadol Contramid OAD provides
      a rapid rise in plasma concentrations and an equivalent daily systemic exposure
      as tramadol IR, with a reduction in peak plasma concentrations.

PMID- 20051588
TI  - Pharmacokinetic characteristics of bolus-administered mannitol in patients
      undergoing elective craniotomy.
AB  - To better understand mannitol pharmacokinetics, the authors constructed and
      compared population models for high-versus low-dose bolus infusions in humans.
      Patients (aged 18-75, American Society of Anesthesiologists physical status 1-3)
      scheduled for elective craniotomy with an anticipated need for intraoperative
      mannitol were randomly assigned to receive either 0.5 (n = 10) or 1.0 (n = 12)
      g/kg of 20% mannitol over 15 minutes. Serial blood samples were collected at the
      predetermined intervals over 12 hours. Plasma mannitol concentrations were
      measured by gas chromatography and subjected to pharmacokinetic analysis; a 3
      compartment model best described mannitol disposition characteristics. Weight and
      dose were the important covariates for rapid peripheral volume of distribution
      (V2) and central clearance (CL1), respectively. Estimated population means were
      2.80, 8.86, and 12.0 L for central (V1), rapid (V2), and slow (V3) volumes of
      distribution, respectively. Clearances of the central compartments (CL1) were
      0.07 versus 0.04 L/min in the high-versus low-dose group, respectively. Thus,
      mannitol kinetics can be considered as nonlinear. Clearances of the rapid
      peripheral (CL2) and slow peripheral compartments (CL3) were identical (2.07 and
      0.16 L/min) in both. The current weight-based dosing guidelines yielded greater
      than expected plasma drug concentrations in obese patients.

PMID- 20051589
TI  - Intimate partner violence and depression in a population-based sample of women:
      can social support help?
AB  - Data from the 2006 Behavioral Risk Factor Surveillance System in Nevada was
      analyzed to determine whether social support is independently associated with
      depression in a population-based sample of women with a history of intimate
      partner violence (IPV). More than a quarter (27%) of the women who were randomly
      chosen to participate in the survey reported lifetime IPV (n = 472). Twenty-four
      percent of abused women were categorized as currently depressed according to the
      eight-item Patient Health Questionnaire (PHQ). Abused women who reported low
      social support, adjusted odds ratio (AOR) = 4.95, 95% CI (1.69-14.49), or
      moderate social support, AOR = 2.71, 95% CI (1.00-7.33), were more likely to be
      depressed than women who reported high levels of social support. Other
      independent risk factors for depression included younger age, AOR = 5.36, 95% CI
      (1.36-25.39); low education (less than high school), AOR = 12.55, 95% CI (2.78
      56.72); fair or poor perceived health status, AOR = 3.72, 95% CI (1.39-9.87);
      being overweight or obese, AOR = 3.21, 95% CI (1.26-8.19); having experienced
      sexual IPV, AOR = 4.95, 95% CI (1.08-22.74); and having experienced both physical
      and sexual IPV, AOR = 4.54, 95% CI (2.07-9.99). There is an urgent need for
      routine screening for IPV and depression in clinic and community settings.
      Interventions that target younger women who experience IPV and aim to decrease
      depression in this vulnerable population are likely to be most effective if they
      promote social support, increase education opportunities, and support healthy
      weight loss behaviors.

PMID- 20051590
TI  - 2009: signaling breakthroughs of the year.
AB  - Nominations for this year's signaling breakthroughs spanned physiology,
      therapeutics and drug development, neuroscience, and plant signaling. Among the
      most exciting advances in mammalian biology were therapeutic applications of
      research that are overturning the conventional boundaries of signaling
      pathways,unexpected mechanisms to prolong life and prevent aging, new insights
      into schizophrenia and memory, development of a transgenic primate model, and the
      discovery that the cells in the lungs can "taste" noxious substances. In plant
      signaling,the nominations converged on the identification of the elusive receptor
      for the plant stress hormone abscisic acid. Finally, methodological advances were
      also noted with new techniques in synthetic biology enabling the precise
      spatiotemporal control of signaling events and increasingly facile methods for
      creation and analysis of proteomic data yielding tremendous increases in raw data
      and insights into cellular regulation.

PMID- 20051592
TI  - New endogenous regulators of class I histone deacetylases.
AB  - Gene expression in eukaryotes depends on epigenetic changes that occur on both
      histones and DNA. Class I histone deacetylases (HDACs) are enzymes that remove
      acetyl groups from histones and other nuclear proteins, thereby inducing
      chromatin condensation and transcriptional repression. HDACs belong to a large
      family of enzymes that undergo posttranslational modifications after the
      activation of several intracellular pathways. However, the environmental stimuli
      that change nuclear HDAC functions remain largely unknown. New evidence has
      demonstrated that the lipid sphingosine-1-phosphate (S1P) inhibits the activity
      of HDAC1 and HDAC2. Both S1P and sphingosine kinase 2 (SphK2), the enzyme that
      synthesizes S1P, are assembled in corepressor complexes containing HDAC1 and
      HDAC2. S1P is among the few endogenous HDAC inhibitors that is synthesized in the
      nucleus in response to extracellular stimulation, and the first nuclear lipid
      associated with an epigenetic modification. The discovery of endogenous molecules
      that regulate HDAC activity in vivo has implications for the development of new
      therapeutic approaches for a host of human diseases, including cancer and
      neurodegenerative disorders.

PMID- 20051594
TI  - Mentoring practices in radiologic science education.
AB  - BACKGROUND: Mentoring in health science education programs has gained popularity
      over the past 20 years and is associated with increased self-confidence and self
      esteem and decreased stress and anxiety. OBJECTIVE: To determine the extent of
      mentoring practices within the radiologic sciences. METHODS: An online survey was
      administered to 125 radiography programs in the southeastern United States
      accredited by the Joint Review Committee on Education in Radiologic Technology.
      RESULTS: Of the 36 respondents, only 22% had formal mentoring programs. The
      majority believed their mentoring program had a positive effect on student
      retention and was somewhat successful. CONCLUSION: Future research involving a
      larger population of radiologic science programs would be beneficial.

PMID- 20051593
TI  - Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus
      formation in mice lacking phospholipase D1.
AB  - Platelet aggregation is essential for hemostasis but can also cause myocardial
      infarction and stroke. A key but poorly understood step in platelet activation is
      the shift of the principal adhesive receptor, alpha(IIb)beta(3) integrin, from a
      low- to high-affinity state for its ligands, a process that enables adhesion and
      aggregation. In response to stimulation of heterotrimeric guanosine triphosphate
      binding protein or immunoreceptor tyrosine-based activation motif-coupled
      receptors, phospholipases cleave membrane phospholipids to generate lipid and
      soluble second messengers. An essential role in platelet activation has been
      established for phospholipase C (PLC) but not for PLD and its product
      phosphatidic acid. Here, we report that platelets from Pld1(-/-) mice displayed
      impaired alpha(IIb)beta(3) integrin activation in response to major agonists and
      defective glycoprotein Ib-dependent aggregate formation under high shear
      conditions. These defects resulted in protection from thrombosis and ischemic
      brain infarction without affecting tail bleeding times. These results indicate
      that PLD1 may be a critical regulator of platelet activity in the setting of
      ischemic cardiovascular and cerebrovascular events.

PMID- 20051595
TI  - Radiographers and the internet: an Australian perspective.
AB  - BACKGROUND: The Internet is an important information source for health
      practitioners, yet little is known about how radiographers currently are using
      this vast information resource for professional development. OBJECTIVE: To
      provide an initial data set on professional use of Internet tools and resources
      by Australian radiographers. METHODS: In 2007, 1142 medical radiation science
      practitioners in Australia were mailed a survey about Internet access at work and
      their Internet use for updating professional knowledge. This article reports on
      and analyzes the survey responses from radiographers. RESULTS: The vast majority
      of radiographer respondents (93.9%) reported having Internet access at work and
      many use Internet searches, Web pages, e-mail and listserves to update their
      professional knowledge. At the same time, large numbers were unaware of Internet
      based resources. Also, Internet access and protected time for professional
      reading and study varied by practice location (metropolitan vs nonmetropolitan).
      CONCLUSION: Knowledge gaps regarding the Internet and lack of uniform Internet
      access among Australian radiographers must be addressed so that all radiographers
      can benefit from the professional information available online.

PMID- 20051596
TI  - Nuclear imaging in breast cancer.
AB  - Nuclear imaging of the breast shows physiological changes that usually are due to
      malignancies. These changes are detectable earlier than those visible on other
      imaging modalities. Recent advances in functional breast imaging have given us
      promising new tools - positron emission mammography and breast-specific gamma
      imaging - that combine the advantages of functional imaging with a finer
      resolution than that of positron emission tomography and scintimammography. If
      its promises bear out, breast-specific functional imaging will provide a powerful
      new tool in the fight against breast cancer and will assume a larger role in the
      coming years.

PMID- 20051597
TI  - Removing Minus-density Artifacts.

PMID- 20051598
TI  - Gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a widespread, chronic condition common
      in the Western world. More than 25 million Americans experience heartburn or
      other GERD symptoms weekly. However, controversy surrounds its diagnosis and
      treatment because not all patients with GERD have heartburn and not all patients
      with heartburn have GERD. Radiologic technologists can better serve their
      patients by understanding this common yet complicated disease and the tests used
      to diagnose it.

PMID- 20051599
TI  - Presenting and illustrating data.

PMID- 20051600
TI  - Academic misconduct and detection.

PMID- 20051601
TI  - Minimizing grid cutoff.

PMID- 20051602
TI  - Technician or technologist?

PMID- 20051603
TI  - More on fluoroscopic positioning.

PMID- 20051604
TI  - Upper GI Series/Serie del Tubo Digestivo Superior.

PMID- 20051605
TI  - Predictors of change in grip strength over 3 years in the African American health
      project.
AB  - OBJECTIVE: To examine factors associated with change in grip strength. METHOD:
      Grip strength was measured at baseline and 3 years later. Change was divided into
      "decreased >/=5 kg," "increased >/=5 kg," and "no change" and analyzed using
      multinomial multivariable logistic regression. RESULTS: Decline in grip strength
      was more likely for men, those reporting having cardiovascular disease, and those
      with instrumental activities of daily living, lower body functional limitations,
      high diastolic blood pressure, higher physical activity, and greater body mass.
      Decline was less likely among those ever having Medicaid, those with basic
      activities of daily living disabilities, and those unable to see a doctor in past
      year due to cost. Gain in grip strength was more likely for men and those with
      instrumental activities of daily living disabilities, lower body functional
      limitations, high diastolic blood pressure, and higher physical activity; it was
      less likely for older participants. DISCUSSION: Results can be used to design
      interventions to improve strength outcomes.

PMID- 20051606
TI  - Ageing, neurodegeneration and Parkinson's disease.
AB  - Age is the largest risk factor for the development and progression of Parkinson's
      disease (PD). Ageing affects many cellular processes that predispose to
      neurodegeneration, and age-related changes in cellular function predispose to the
      pathogenesis of PD. The accumulation of age-related somatic damage combined with
      a failure of compensatory mechanisms may lead to an acceleration of PD with age.
      The formation of Lewy bodies may represent a marker for protective mechanisms
      against age-related dysfunction and degeneration of the nervous system. Mild
      parkinsonian signs may be present in older people, which are associated with
      reduced function. These may be due to age-related decline in dopaminergic
      activity, incidental Lewy body disease, degenerative pathologies (early PD and
      Alzheimer's disease) or vascular pathology. Ageing may affect the clinical
      presentation of PD with altered drug side effects, increased risk of developing
      dementia and an increased likelihood of admission to a nursing home. Progression
      of PD, including the development of dementia, and hallucinations is related to
      the age of the patient rather than the age of disease onset. PD may reflect a
      failure of the normal cellular compensatory mechanisms in vulnerable brain
      regions, and this vulnerability is increased by ageing. PD is one of the best
      examples of an age-related disease.

PMID- 20051607
TI  - Identifying frailty in high functioning older adults with normal mobility.

PMID- 20051608
TI  - Unusual reactions to 5-HT3 receptor antagonists in a child with rhabdomyosarcoma.
AB  - A case of unusual reactions consisting of involuntary abnormal facial movements
      in a child following exposure to the 5-HT3 receptor antagonists for prophylaxis
      against chemotherapy-induced vomiting is presented. Potential mechanisms for
      these reactions are discussed.

PMID- 20051609
TI  - Relationship between antiepileptic drugs and biological markers affecting long
      term cardiovascular function in children and adolescents.
AB  - BACKGROUND: Epilepsy is a neurological disorder, relatively common in the
      paediatric population. These children are often treated with antiepileptic drugs
      (AEDs) for several years. The consequence of such long-term exposure may lead to
      variations in plasma homocysteine and serum lipoprotein concentrations.
      OBJECTIVE(S): To review the cardiovascular effects of anticonvulsant therapy and
      their use in childhood epilepsy with special reference to homocysteine and
      lipoprotein. METHODS: A literature search was conducted on PubMed (1966-May 2009)
      and MEDLINE (1966-May 2009). Key terms included antiepileptic drugs, epilepsy,
      homocysteine, cardiovascular events, and children. RESULTS: Certain AEDs
      including carbamazepine, phenobarbital, phenytoin and valproic acid, as well as
      the presence of a homozygous 5-methylenetetrahydrofolate reductase polymorphism
      in the genotype, are potential causes of elevation in plasma homocysteine and
      serum lipoprotein concentrations. CONCLUSIONS: Persistent elevation in these
      biochemical markers has shown to be associated with the development of long-term
      sequelae such as cardiovascular diseases, prompting concerns about the long-term
      implications of chronic AED use in children and cardiovascular risk. Further
      research is needed to assess the relationship between specific chronic AED use,
      homocysteine and lipoprotein concentrations, the influence of genotype, as well
      as the risk of long-term sequelae in the paediatric population.

PMID- 20051610
TI  - Alcohol content in declared non-to low alcoholic beverages: implications to
      pregnancy.
AB  - BACKGROUND: Alcohol consumption in pregnancy may result in serious adverse fetal
      outcome. Non- or low alcoholic wines and beers may be a risk-reduction strategy
      to help alcohol-dependent individuals to prevent or limit ethanol consumption.
      The objective of this study was to quantify ethanol concentrations in Canadian
      beverages claiming to contain no or low alcohol content. METHODS: Forty-five
      different beverages claiming to contain no or low alcohol content in the Canadian
      market were tested for ethanol concentration using gas chromatography. RESULTS:
      Thirteen (29%) of the beverages contained ethanol levels higher than the declared
      concentration on their label. Six beverages claiming to contain no alcohol were
      found to contain greater than 1% ethanol. CONCLUSION: Pregnant women seeking
      replacement to alcoholic beverages may be misled by these labels, unknowingly
      exposing themselves and their unborn babies to ethanol.

PMID- 20051611
TI  - Synthesis and characterization of ultra-fine Y2O3:Eu3+ nanophosphors for
      luminescent security ink applications.
AB  - We report a simple method for the synthesis of ultra-fine Eu(3+)-doped yttria
      (Y(2)O(3)) nanophosphors with an average diameter of approximately 5 nm for
      development of a transparent colloid that could be used as a luminescent security
      ink. This has been achieved by suitably substituting Eu(3+) ions at the favorable
      C(2) symmetry sites of Y(3+) ions and quantum mechanically confining the growth
      of the nanophosphor using a novel acid-catalyzed sol-gel technique. This is one
      of the few reports that depict the development of a transparent aqueous-stable
      Y(2)O(3):Eu(3+) colloidal solution for strategic applications related to security
      codes. High resolution transmission electron microscopy images showed excellent
      lattice fringes that in turn support the presence of better crystal quality and
      enhanced photoluminescence (PL) emission from the Y(1.9)O(3)Eu(0.1)(3+)
      nanophosphor system. Time resolved emission spectroscopy measurement indicated a
      PL decay time in the range of a few milliseconds, suitable for making luminescent
      security ink and other advanced applications in optoelectronic devices and bio
      labeling.

PMID- 20051612
TI  - Fabrication of single-phase titanium carbide layers from MWCNTs using high DC
      pulse.
AB  - Single-phase layered titanium carbide (TiC) was successfully synthesized by
      reacting carbon nanotubes (CNTs) and titanium dioxide (TiO2) under a high direct
      current (DC) pulse. Single-phase TiC layer fabrication is confirmed as the
      transformation of multi-layered graphene from MWCNTs. Therefore its thickness and
      width is almost identical to those of transformed graphene layers. This is the
      first report on the formation of single-phase layered nano-TiC. Scanning electron
      microscopy (SEM), x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS)
      and high-resolution transmission electron microscopy (HR-TEM) were used for the
      characteristic analysis of single-phase layered TiC structures.

PMID- 20051613
TI  - Biofabrication methods for the patterned assembly and synthesis of viral
      nanotemplates.
AB  - This paper reports on novel methodologies for the patterning and templated
      synthesis of virus-structured nanomaterials in two- and three-dimensional
      microfabricated architectures using the Tobacco mosaic virus (TMV). The TMV is a
      high aspect ratio biological molecule which can be engineered to include amino
      acids with enhanced binding properties. These modifications facilitate self
      assembly of the TMV onto various substrates and enable its use as a template for
      the synthesis of nanostructured materials. This work focuses on the combination
      of this bottom-up biologically inspired fabrication method with standard top-down
      micromachining processes that allow direct integration of the virus-structured
      materials into batch-fabricated devices. Photolithographic patterning of uncoated
      as well as nickel-coated TMV nanostructures has been achieved using a lift-off
      process in both solvent and mild basic solutions and their assembly onto three
      dimensional polymer and silicon microstructures is demonstrated. In addition to
      these patterning techniques, in situ formation of metal oxide TMV coatings in
      patterned microfabricated environments is shown using atomic layer deposition
      directly on the nickel-coated viruses. The biofabrication 'process toolbox'
      presented in this work offers a simple and versatile alternative for the
      hierarchical patterning and incorporation of biotemplated nanomaterials into
      micro/nanofabrication schemes.

PMID- 20051614
TI  - Position-controlled AlN/ZnO coaxial nanotube heterostructure arrays for electron
      emitter applications.
AB  - We studied the fabrication and field-emission characteristics of position
      controlled AlN/ZnO nanotube heterostructure arrays. AlN layers with various
      thicknesses from 20 to 52 nm were deposited coaxially on the position-controlled
      ZnO nanotube arrays. The field-emission properties of the coaxial AlN/ZnO
      nanotube arrays were controlled using the AlN thickness and the nanotube
      interdistance. As compared to the bare ZnO nanotube arrays, the AlN-coated
      coaxial nanotube arrays exhibited enhanced electron emission, and the optimum AlN
      coating layer thickness on the nanotube tips was 26 nm. The improved field
      emission from the coaxial nanotube heterostructures is attributed to the low
      electron affinity and the thickness modulation effect of the AlN coating layer.

PMID- 20051615
TI  - Wireless solutions for managing diabetes: A review and future prospects.
AB  - Diabetes is rapidly growing in prevalence worldwide. The number of people with
      diabetes was 171 million in 2000 and will grow to 366 million by 2030. One reason
      for this is a growing elderly population, but younger people are increasingly
      likely to develop diabetes due to an increase in mean weight and a decrease in
      exercise. The increasing resources needed to modify lifestyle and appropriately
      manage diabetes are a worldwide healthcare burden. Promising solutions arise
      among others from wireless technologies and mobile solutions. In this paper, the
      needs for information, change in lifestyle, health monitoring, and management of
      medication and complications in diabetes are analysed. They form a basis for
      following review of available wireless solutions for managing diabetes. Finally,
      future prospects of mobile management of diabetes are discussed.

PMID- 20051616
TI  - Comparison of a manual and motorized stiffness meter to quantify bone
      regeneration in distraction osteogenesis.
AB  - To assess bone healing and investigate the influence of different pharmaceutics
      (e.g. growth factors) on bone stiffness and strength in-vivo, new quantitative
      methods are necessary. Therefore, a new manual and motorized stiffness meter to
      quantify bone regeneration in a model of distraction osteogenesis were compared.
      The design, equipment, and improvements of the measurement devices are described.
      Furthermore, their difference in precision and accuracy in comparison to tests
      from a material testing system, used as "gold standard", were evaluated. Both
      devices were able to assess regenerate stiffness: the accuracy ranged between +/-
      9% for the manual and +/-5% for the motorized version for stiffness data over 0.1
      Nm/ degrees; precision between +/- 3.8% for the manual and +/- 3.2% for the
      motorized device. In summary, the two stiffness measurement devices described in
      this study have the power to monitor the beginning of bone healing and therefore
      predict the load bearing capacity of regenerating bone. The motorized version
      showed advantages over the manual device when investigating and monitoring the
      stiffness of bone during a consolidation period: (1) better accuracy in both
      stiffness below and above 0.1 Nm/ degrees, (2) a better precision in the
      stiffness range of interest, (3) easier handling, and (4) standardisation of the
      measurement process using the stepper motor and definition of the maximums of
      torque, angulation and rotation speed.

PMID- 20051617
TI  - Anaemia in older people with chronic heart failure: The potential cost.
AB  - Studies suggest benefits from correcting anaemia in heart failure using a
      combination of erythropoiesis-stimulating agents (ESAs) and intravenous iron. We
      set out to investigate the number of older patients who would require treatment
      of anaemia in a large teaching hospital in the United Kingdom and the cost
      implications. The prevalence of anaemia and chronic kidney disease (CKD) in
      patients 65 years and older with systolic dysfunction attending the local heart
      failure clinic was determined. The projected numbers of patients in our health
      district who would meet published kidney disease guidelines for treatment of
      anaemia was then estimated. The costs of treatment with combination ESAs and IV
      iron were calculated for these patients based on the treatment costs for renal
      anaemia in our local renal unit. Sensitivity analysis for different thresholds of
      haemoglobin and eGFR was performed. In our study of 86 heart failure patients,
      mean age 81 years, 34% have anaemia and 73% have stage III CKD with estimated
      glomerular filtration rate < 60 ml/min/1.73 cm2. At the haemoglobin threshold
      value of <of=11.0 g/dl for treatment of anaemia in heart failure patients with
      stage III CKD, 1031 elderly heart failure patients in our health district (total
      population 424,654) would require treatment with IV iron and erythropoietin, at a
      cost of pound2.7 million per annum. The estimated cost of treating anaemia in
      elderly patients with heart failure using ESAs and IV iron is substantial and its
      cost effectiveness is unknown.

PMID- 20051618
TI  - Effect of 6 weeks wobble board exercises on static and dynamic balance of stroke
      survivors.
AB  - Balance is a complex motor skill and it is frequently disturbed among stroke
      survivors. Rehabilitation experts are still facing challenges in achieving good
      stability. The primary aim of this study was to determine the effect of a wobble
      board exercise program on static and dynamic balance of hemiplegic subjects.
      Seventeen (17) stroke survivors were randomly selected into two groups. The
      subjects in the experimental group were trained on wobble board for six weeks
      while the control group received only the baseline treatment programs. The
      modified version of the timed balance test was used to assess balance while the
      foursquare step test was used to assess dynamic balance. Descriptive statistics
      and Analysis of variance (ANOVA) were used to analyze the data obtained. The
      result showed that there was significant difference in the static balance (eye
      closed) (F=7.49, P< 0.05) and dynamic balance (F3.20, P< 0.05) between the groups
      but there was no significant difference in static balance (eye opened) (F= 1.75,
      P> 0.05). The study concluded that wobble board exercise improved both static
      (eye closed) and dynamic balance of stroke survivor used in this study.

PMID- 20051619
TI  - Mechanical gluteal soft tissue material parameter validation under complex tissue
      loading.
AB  - BACKGROUND: Finite element (FE) simulations of mechanical tissue loading help
      provide insight into internal tissue stress and strain distribution. Thus, better
      understanding of pressure sore aetiology and pressure sore prophylaxis can be
      acquired. Indispensable in the simulation process is adequate mechanical
      description of interacting soft tissue and body support materials. Sufficient
      verification of employed material parameters is required. METHOD OF APPROACH:
      Gluteal soft tissue material parameters, previously derived from experimental
      tissue indentation of a geometrically limited buttock sub-domain are shown to be
      suitable in simulating complex deformation of the entire buttocks. In the context
      of parameter verification, defined tissue loading via a soft foam material
      specimen was performed. Making use of magnetic resonance imaging (MRI), the
      scenario was scanned to gain tissue displacement information. Anatomical surface
      data was reconstructed and an FE-model of the experimental situation was
      generated and simulated. MR-image information was compared with simulation
      results. RESULTS: Deformation of gluteal skin/fat and passive muscle tissue and
      support material under loading was in good agreement with the corresponding MR
      image data. Visual accordance was found for deformed skin boundary as well as for
      internal fat-muscle tissue boundaries by superimposing experimental and numerical
      output. In addition, section surface boundaries of the MR-images and the FE-model
      of skin/fat and muscle at the deformed state were discretized and sufficient
      sample points were provided. A correlation factor of R2= 0.998 for skin/fat
      deformation was derived, comparing simulation with MRI output. CONCLUSION:
      Reliability of employed tissue material parameters for use in realistic loading
      scenarios at finite strains including complex tissue and bone anatomy, non-linear
      tissue support material, multiple tissue types and contact interactions is shown.

PMID- 20051620
TI  - An animal model to study ACL reconstruction during growth.
AB  - Controversy exists in the literature regarding the most appropriate treatment for
      anterior cruciate ligament (ACL) ruptures in the skeletally immature patient. To
      study the histological and biomechanical stages following ACL reconstruction
      during growth, it is necessary to establish an equivalent model to replicate the
      situation of an immature skeleton. In the present study we evaluated a large
      animal model of ACL reconstruction during growth using skeletally immature sheep.
      In contrast to existing models we did not intend to provoke growth disturbances.
      Instead, we identified those criteria known to be essential to prevent growth
      disturbances in the human situation and transformed them into an animal model.
      Applying those criteria to skeletally immature sheep at an age of four months, we
      performed a fully transphyseal ACL reconstruction of their right knee. The
      contralateral knee served as a control. The sheep were then sacrificed 3, 6, 12
      and 24 weeks after surgery. This animal model is described in detail in the
      present manuscript. Basic science data are presented in order to 1) make it
      easier for other research groups to study ACL reconstruction during growth using
      our model and 2) to improve this model by modifying the one or other detail of
      the proposed technique. Using this model, remaining open questions concerning ACL
      reconstruction during growth can be addressed in future studies.

PMID- 20051621
TI  - Fabrication of patient specific fasciaform molds for formaldehyde fasciaform
      grafting tympanoplasty.
AB  - In this paper, we report a procedure for making a patient specific Fasciaform
      Mold for a Formaldehyde Fasciaform Grafting Tympanoplasty procedure based on
      Computer Tomography (CT) of the patient's temporal bone. Three dimensional ear
      canal models were first reconstructed from the CT scans of patients. The models
      were then used by CNC (Computer Numeric Control) machines for making stainless
      steel molds as well as rapid prototyping machines for producing acrylic based
      polymer molds. Both a stainless steel mold and a pair of plastic acrylic molds
      were produced for Formaldehyde Fasciaform Grafting Tympanoplasty. The procedure
      is found to be feasible in producing a patient specific fasciaform mold within a
      reasonable time.

PMID- 20051623
TI  - Chapter 1: Diagnostic Medical Imaging: X-ray projection technique, image
      subtraction method, direct digital x-ray imaging, computed tomography (CT).

PMID- 20051624
TI  - Gait analysis and synthesis: Biomechanics, orthotics, prosthetics.

PMID- 20051625
TI  - Oncostatin M promotes bone formation independently of resorption when signaling
      through leukemia inhibitory factor receptor in mice.
AB  - Effective osteoporosis therapy requires agents that increase the amount and/or
      quality of bone. Any modification of osteoclast-mediated bone resorption by
      disease or drug treatment, however, elicits a parallel change in osteoblast
      mediated bone formation because the processes are tightly coupled. Anabolic
      approaches now focus on uncoupling osteoblast action from osteoclast formation,
      for example, by inhibiting sclerostin, an inhibitor of bone formation that does
      not influence osteoclast differentiation. Here, we report that oncostatin M (OSM)
      is produced by osteoblasts and osteocytes in mouse bone and that it has distinct
      effects when acting through 2 different receptors, OSM receptor (OSMR) and
      leukemia inhibitory factor receptor (LIFR). Specifically, mouse OSM (mOSM)
      inhibited sclerostin production in a stromal cell line and in primary murine
      osteoblast cultures by acting through LIFR. In contrast, when acting through
      OSMR, mOSM stimulated RANKL production and osteoclast formation. A key role for
      OSMR in bone turnover was confirmed by the osteopetrotic phenotype of mice
      lacking OSMR. Furthermore, in contrast to the accepted model, in which mOSM acts
      only through OSMR, mOSM inhibited sclerostin expression in Osmr-/- osteoblasts
      and enhanced bone formation in vivo. These data reveal what we believe to be a
      novel pathway by which bone formation can be stimulated independently of bone
      resorption and provide new insights into OSMR and LIFR signaling that are
      relevant to other medical conditions, including cardiovascular and
      neurodegenerative diseases and cancer.

PMID- 20051626
TI  - CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in
      xenografts.
AB  - Recent evidence suggests that breast cancer and other solid tumors possess a rare
      population of cells capable of extensive self-renewal that contribute to
      metastasis and treatment resistance. We report here the development of a strategy
      to target these breast cancer stem cells (CSCs) through blockade of the IL-8
      receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or
      repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC
      population in 2 human breast cancer cell lines in vitro. Furthermore, this was
      followed by the induction of massive apoptosis in the bulk tumor population via
      FASL/FAS signaling. The effects of CXCR1 blockade on CSC viability and on FASL
      production were mediated by the FAK/AKT/FOXO3A pathway. In addition, repertaxin
      was able to specifically target the CSC population in human breast cancer
      xenografts, retarding tumor growth and reducing metastasis. Our data therefore
      suggest that CXCR1 blockade may provide a novel means of targeting and
      eliminating breast CSCs.

PMID- 20051627
TI  - Heart failure causes cholinergic transdifferentiation of cardiac sympathetic
      nerves via gp130-signaling cytokines in rodents.
AB  - Although several cytokines and neurotrophic factors induce sympathetic neurons to
      transdifferentiate into cholinergic neurons in vitro, the physiological and
      pathophysiological roles of this remain unknown. During congestive heart failure
      (CHF), sympathetic neural tone is upregulated, but there is a paradoxical
      reduction in norepinephrine synthesis and reuptake in the cardiac sympathetic
      nervous system (SNS). Here we examined whether cholinergic transdifferentiation
      can occur in the cardiac SNS in rodent models of CHF and investigated the
      underlying molecular mechanism(s) using genetically modified mice. We used Dahl
      salt-sensitive rats to model CHF and found that, upon CHF induction, the cardiac
      SNS clearly acquired cholinergic characteristics. Of the various cholinergic
      differentiation factors, leukemia inhibitory factor (LIF) and cardiotrophin-1
      were strongly upregulated in the ventricles of rats with CHF. Further, LIF and
      cardiotrophin-1 secreted from cultured failing rat cardiomyocytes induced
      cholinergic transdifferentiation in cultured sympathetic neurons, and this
      process was reversed by siRNAs targeting Lif and cardiotrophin-1. Consistent with
      the data in rats, heart-specific overexpression of LIF in mice caused cholinergic
      transdifferentiation in the cardiac SNS. Further, SNS-specific targeting of the
      gene encoding the gp130 subunit of the receptor for LIF and cardiotrophin-1 in
      mice prevented CHF-induced cholinergic transdifferentiation. Cholinergic
      transdifferentiation was also observed in the cardiac SNS of autopsied patients
      with CHF. Thus, CHF causes target-dependent cholinergic transdifferentiation of
      the cardiac SNS via gp130-signaling cytokines secreted from the failing
      myocardium.

PMID- 20051629
TI  - Let's keep this brief.
AB  - The regular articles and technical advances published in this issue are an
      average of 9,050 words, with 8.4 display items (figures and tables). Do we always
      need so many words to convey a message? We think not. With this editorial, we
      issue a call for brief reports.

PMID- 20051628
TI  - TLR4 signaling in effector CD4+ T cells regulates TCR activation and experimental
      colitis in mice.
AB  - TLRs sense various microbial products. Their function has been best characterized
      in DCs and macrophages, where they act as important mediators of innate immunity.
      TLR4 is also expressed on CD4+ T cells, but its physiological function on these
      cells remains unknown. Here, we have shown that TLR4 triggering on CD4+ T cells
      affects their phenotype and their ability to provoke intestinal inflammation. In
      a model of spontaneous colitis, Il10-/-Tlr4-/- mice displayed accelerated
      development of disease, with signs of overt colitis as early as 8 weeks of age,
      when compared with Il10-/- and Il10-/-Tlr9-/- mice, which did not develop colitis
      by 8 months. Similar results were obtained in a second model of colitis in which
      transfer of naive Il10-/-Tlr4-/- CD4+ T cells into Rag1-/- recipients sufficient
      for both IL-10 and TLR4 induced more aggressive colitis than the transfer of
      naive Il10-/- CD4+ T cells. Mechanistically, LPS stimulation of TLR4-bearing CD4+
      T cells inhibited ERK1/2 activation upon subsequent TCR stimulation via the
      induction of MAPK phosphatase 3 (MKP-3). Our data therefore reveal a tonic
      inhibitory role for TLR4 signaling on subsequent TCR-dependent CD4+ T cell
      responses.

PMID- 20051630
TI  - Australian scientists say "G'day USA".

PMID- 20051631
TI  - Stem cells: roadmap to the clinic.
AB  - Over the last decade, a remarkable number of papers have been published in which
      the biology of stem cells is introduced with words and phrases such as "promise,"
      "rapid progress," and "future therapies." To separate myth and hype from reality,
      the articles in this Stem Cells Review series comprise a rich resource on the
      state of this fast-paced field and provide a balanced perspective on some of the
      major advances. They recount what the field has achieved over the past decade and
      where the field is headed. They also highlight the challenges to be faced in
      translating what is indeed highly promising science into proven therapies that
      will regenerate and repair diseased tissues.

PMID- 20051632
TI  - Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells.
AB  - Skeletal muscle damaged by injury or by degenerative diseases such as muscular
      dystrophy is able to regenerate new muscle fibers. Regeneration mainly depends
      upon satellite cells, myogenic progenitors localized between the basal lamina and
      the muscle fiber membrane. However, other cell types outside the basal lamina,
      such as pericytes, also have myogenic potency. Here, we discuss the main
      properties of satellite cells and other myogenic progenitors as well as recent
      efforts to obtain myogenic cells from pluripotent stem cells for patient-tailored
      cell therapy. Clinical trials utilizing these cells to treat muscular
      dystrophies, heart failure, and stress urinary incontinence are also briefly
      outlined.

PMID- 20051633
TI  - Pregenerative medicine: developmental paradigms in the biology of cardiovascular
      regeneration.
AB  - The ability to create new functional cardiomyocytes is the holy grail of cardiac
      regenerative medicine. From studies using model organisms, new insights into the
      fundamental pathways that drive heart muscle regeneration have begun to arise as
      well as a growing knowledge of the distinct families of multipotent
      cardiovascular progenitors that generate diverse lineages during heart
      development. In this Review, we highlight this intersection of the
      "pregenerative" biology of heart progenitor cells and heart regeneration and
      discuss the longer term challenges and opportunities in moving toward a
      therapeutic goal of regenerative cardiovascular medicine.

PMID- 20051634
TI  - Stem cells in human neurodegenerative disorders--time for clinical translation?
AB  - Stem cell-based approaches have received much hype as potential treatments for
      neurodegenerative disorders. Indeed, transplantation of stem cells or their
      derivatives in animal models of neurodegenerative diseases can improve function
      by replacing the lost neurons and glial cells and by mediating remyelination,
      trophic actions, and modulation of inflammation. Endogenous neural stem cells are
      also potential therapeutic targets because they produce neurons and glial cells
      in response to injury and could be affected by the degenerative process. As we
      discuss here, however, significant hurdles remain before these findings can be
      responsibly translated to novel therapies. In particular, we need to better
      understand the mechanisms of action of stem cells after transplantation and learn
      how to control stem cell proliferation, survival, migration, and differentiation
      in the pathological environment.

PMID- 20051635
TI  - The therapeutic promise of the cancer stem cell concept.
AB  - Cancer stem cells (CSCs) are a subpopulation of tumor cells that selectively
      possess tumor initiation and self-renewal capacity and the ability to give rise
      to bulk populations of nontumorigenic cancer cell progeny through
      differentiation. As we discuss here, they have been prospectively identified in
      several human malignancies, and their relative abundance in clinical cancer
      specimens has been correlated with malignant disease progression in human
      patients. Furthermore, recent findings suggest that clinical cancer progression
      driven by CSCs may contribute to the failure of existing therapies to
      consistently eradicate malignant tumors. Therefore, CSC-directed therapeutic
      approaches might represent translationally relevant strategies to improve
      clinical cancer therapy, in particular for those malignancies that are currently
      refractory to conventional anticancer agents directed predominantly at tumor bulk
      populations.

PMID- 20051636
TI  - Progress toward the clinical application of patient-specific pluripotent stem
      cells.
AB  - Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of
      somatic cells through the exogenous expression of transcription factors. These
      cells, just like embryonic stem cells, are likely to have a major impact on
      regenerative medicine, because they self-renew and retain the potential to be
      differentiated into all cell types of the human body. In this Review, we describe
      the current state of iPS cell technology, including approaches by which they are
      generated and what is known about their biology, and discuss the potential
      applications of these cells for disease modeling, drug discovery, and,
      eventually, cell replacement therapy.

PMID- 20051637
TI  - Enabling stem cell therapies through synthetic stem cell-niche engineering.
AB  - Enabling stem cell-targeted therapies requires an understanding of how to create
      local microenvironments (niches) that stimulate endogenous stem cells or serve as
      a platform to receive and guide the integration of transplanted stem cells and
      their derivatives. In vivo, the stem cell niche is a complex and dynamic unit.
      Although components of the in vivo niche continue to be described for many stem
      cell systems, how these components interact to modulate stem cell fate is only
      beginning to be understood. Using the HSC niche as a model, we discuss here
      microscale engineering strategies capable of systematically examining and
      reconstructing individual niche components. Synthetic stem cell-niche engineering
      may form a new foundation for regenerative therapies.

PMID- 20051638
TI  - The bioethics of stem cell research and therapy.
AB  - Discussion of the bioethics of human stem cell research has transitioned from
      controversies over the source of human embryonic stem cells to concerns about the
      ethical use of stem cells in basic and clinical research. Key areas in this
      evolving ethical discourse include the derivation and use of other human
      embryonic stem cell-like stem cells that have the capacity to differentiate into
      all types of human tissue and the use of all types of stem cells in clinical
      research. Each of these issues is discussed as I summarize the past, present, and
      future bioethical issues in stem cell research.

PMID- 20051639
TI  - Evaluation of high-performance liquid chromatography and mass spectrometry method
      for pharmacokinetic study of local anesthetic ropivacaine in plasma.
AB  - We studied the viability of high-performance liquid chromatography and mass
      spectrometry (LC/MS) as a selective and sensitive analytical method for measuring
      blood concentrations of the local anesthetic ropivacaine. Ropivacaine was
      effectively separated using a reverse-phase column and monitored at 275 m/z ion.
      The LC/MS method allowed measurement of concentrations of ropivacaine of lower
      than 75 ng/mL. The standard curve was linear and in the range of <1.5 microg/mL.
      Recovery of ropivacaine in plasma samples was over 90% after precipitation of
      plasma protein with trichloroacetic acid. The method was tested on the
      pharmacokinetics of plasma ropivacaine after single intravenous or subcutaneous
      administration in rabbits. The pharmacokinetic parameters showed a one
      compartment model and a mean elimination half-life of 0.54+/-0.05 h and 2.83+/
      0.51 h after administration at doses of 0.4 mg/kg, i.v. and 5 mg/kg, s.c.,
      respectively. These values were in approximate agreement with previously obtained
      results in dogs. The results of the present study demonstrated that the LC/MS
      method was highly selective and sensitive for the measurement of ropivacaine,
      indicating that it offers a useful tool for monitoring the therapeutic effects
      and determining the pharmacokinetic parameters of this drug in blood.

PMID- 20051640
TI  - Effect of intrauterine undernutrition during late gestation on pancreatic beta
      cell mass.
AB  - We analyzed the effect of low birth weight on pancreatic beta cell mass. We used
      pregnant C57BL6J mice, and we reduced their food supply by 30% during the late
      gestational period and examined the changes in the metabolism and pancreatic beta
      cell mass. Pancreatic beta cell mass at birth was greatly decreased in the mice
      of the food restriction group (RG) as compared to the mice of the control group
      (CG). The body weight of RG mice exhibited a "catch-up growth" pattern and became
      equivalent to that of CG mice 7 days after birth, and thereafter exceeded that of
      CG mice; however, the pancreatic beta cell mass in RG mice remained lower than
      that in CG mice at the age of 4 weeks. A high-fat diet significantly increased
      the pancreatic beta cell mass in RG mice as compared to that in CG mice at 12
      weeks of age. However, RG mice fed on high-fat diets tended to exhibit a decrease
      in the pancreatic beta cell mass at approximately 20 weeks of age. The plasma
      insulin concentrations also tended to be decreased in RG mice after 24 weeks of
      age as compared to those of CG mice. These results thus indicate that the growth
      of pancreatic beta cells is insufficient in RG mice, and pancreatic beta cell
      failure can easily develop as a consequence of insulin resistance.

PMID- 20051641
TI  - Long-term effects of diabetes mellitus on voiding function in a new model of type
      2 diabetes mellitus, the Spontaneously Diabetic Torii (SDT) rat.
AB  - The spontaneously diabetic Torii (SDT) rat has recently been established as a
      model of type 2 diabetes mellitus (DM). The usefulness of this rat model for the
      study of diabetic voiding dysfunction was investigated. Male SDT rats and male
      Sprague-Dawley (SD) rats were used. Voiding function was evaluated by a metabolic
      cage study and cystometry. Total voided volume for 24 h, mean voided volume, and
      urinary frequency for 24 h were significantly greater in SDT rats at the age of
      36 weeks. From cystometry mean inter-micturition interval (IMI) was significantly
      longer in SDT rats at the age of 22 and 36 weeks. In SDT rats mean IMI was
      significantly longer at the age of 36 weeks than at the age of 22 weeks. Mean
      voiding pressure was significantly higher in SDT rats at the age of 22 and 36
      weeks. In the present study, SDT rats showed typical diabetic voiding dysfunction
      similar to other diabetic rat models. It was suggested that activity of the
      bladder afferent pathways is decreased and the urethral relaxation mechanism is
      impaired in SDT rats. In addition, SDT rats are suitable to study chronic
      diabetic voiding dysfunction because they survive without insulin treatment for
      as long as 60 weeks.

PMID- 20051642
TI  - Age-related changes in contraction and relaxation of rat diaphragm.
AB  - Age-related changes of physiological and biochemical properties were examined in
      the diaphragm muscle, which has particularly high activation compared to that of
      other skeletal muscles. The diaphragm from 10-week-, 50-week- and 100-week-old
      male Wistar rats were used to measure in vitro isometric contractile properties,
      sarcoplasmic reticulum (SR) Ca2+-ATPase activity, and myosin heavy chain (MHC)
      isoform composition. Although there were no significant differences in specific
      twitch tension of the diaphragm among the groups, there was significant reduction
      in specific tetanic tension in the 50-week to 100-week groups. The contraction
      time and 1/2 relaxation time of twitch contraction extended with aging, and
      significant differences were found between 10-week-old and 100-week-old
      diaphragms. Regarding the activity of SR Ca2+-ATPase, the pattern of age-related
      change was similar to that in the 1/2 relaxation time and there was a significant
      difference between 10-week-old and 100-week-old diaphragms. There was a
      significant increase in the relative composition of the MHC I isoform in 100-week
      diaphragms compared to that in 10-week-old diaphragms and a concomitant decrease
      in the relative composition of fast myosin was noted. These findings demonstrated
      that older diaphragms have slower contraction and relaxation speeds, and these
      alterations were attributed to changes in SR Ca2+-ATPase activity and MHC isoform
      composition.

PMID- 20051643
TI  - A higher level of prostaglandin E2 in the urinary bladder in young boys and boys
      with lower urinary tract obstruction.
AB  - We conducted two studies to examine the hypothesis that lower urinary tract
      obstruction induces excessive production of prostaglandin E2 (PGE2) in the
      bladder in young boys, with consequent overactive bladder (OAB) symptoms. The
      subjects were boys aged less than 15 years old who were scheduled to undergo
      surgery in our department from October 2006 to March 2008. In study 1 (n=25), the
      patients were divided into two groups based on the presence or absence of lower
      urinary tract obstruction. In study 2 (n=38), the patients were classified by
      age. The PGE2 level in the bladder was determined by washing with saline before
      the operation and urinary symptoms were evaluated using the Pediatric Lower
      Urinary Tract Scoring System. In study 1, the PGE2 level in the bladder of
      patients with lower urinary tract obstruction was higher than in those without
      obstruction (49.1+/-37.4 vs. 21.5+/-10.1 pg/mL, P=0.0475). In study 2, the PGE2
      level in the bladder was negatively correlated with age (r=-0.379, P=0.0207). A
      higher level of PGE2 is found in boys with bladder outlet obstruction due to
      urethral stricture and in younger boys, and this elevated level of PGE2 may
      induce OAB symptoms.

PMID- 20051644
TI  - Relationship between endothelin-1 and interleukin-1beta in inflamed periodontal
      tissues.
AB  - We recently demonstrated that endothelin-1 (ET-1) was strongly expressed in
      inflamed gingival tissues, but the biological role of ET-1 in gingival tissue
      remains unknown. This study focused on the relationship between ET-1 and
      interleukin-1beta (IL-1beta), an important cytokine during the periodontal
      inflammatory process. We determined the protein levels of ET-1 and IL-1beta in
      gingival tissues from patients and examined whether ET-1 could regulate the
      expression of the IL-1beta gene and protein in oral epithelial cells and
      fibroblasts in vitro. There was a significant correlation between the levels of
      ET-1 and IL-1beta in 26 gingival tissues, as determined by ELISA. Following the
      confirmation of two specific ET-1 receptors (ETA and ETB receptors) on the
      cultured cells, the effects of ET-1 stimulation on IL-1beta mRNA and protein
      expression were evaluated by RT-PCR and ELISA, respectively. The IL-1beta mRNA
      and protein levels were enhanced by ET-1 stimulation in a dose-dependent manner,
      and the enhancement of IL-1beta was inhibited by ETA or ETB receptor antagonists.
      These findings indicate that ET-1 is involved in the regulation of IL-1beta
      expression in gingival tissues and suggest that ET-1 signaling to the cells may
      be a therapeutic target for treating IL-1beta-dependent inflammatory responses.

PMID- 20051645
TI  - Circadian characteristics of mice depleted with GPR7.
AB  - GPR7, now known as a receptor of neuropeptide B and neuropeptide W, is expressed
      in neurons of the suprachiasmatic nucleus (SCN), the mammalian circadian center.
      By the quantitative in situ hybridization, we demonstrated that GPR7 mRNA showed
      a significant circadian rhythm in the SCN showing a peak at early subjective
      night in both light-dark and constant dark. We characterized the circadian
      feature of GPR7-knockout mice, but the period length and the phase-dependent
      phase shift to light exposure were not disordered in GPR7-knockout mice.
      Moreover, the food-anticipatory behavior in restricted feeding schedule was
      observed in this gene-deleted mouse similar to wild-type. These results indicate
      that the role of GPR7 may be subtle or limited in relation to the circadian clock
      despite its robust expression in the SCN.

PMID- 20051646
TI  - Suppressive effects of a cyanine dye against herpes simplex virus (HSV)-1
      infection.
AB  - In this study, we demonstrate that a cyanine dye, lumin, significantly suppressed
      cytopathic effect by herpes simplex virus (HSV)-1 toward human amnionic FL cell
      and also it reduced replication of HSV-1 in a dose-dependent manner. In addition,
      lumin additively augmented the antiviral effect of interferon (IFN)-alpha.
      Furthermore, fluorescence microscopic study showed that lumin (not IFN-alpha)
      itself remarkably induced alkalinization of intracellular organelle, suggesting
      the inhibition of virus invasion into the cells. These results suggest that lumin
      exerts an antiviral action against HSV-1 with the independent pathways of IFN
      alpha and also it would become a therapeutically effective drug in clinical
      practice.

PMID- 20051647
TI  - Association of the common fat mass and obesity associated (FTO) gene polymorphism
      with obesity in a Japanese population.
AB  - The association of the FTO gene polymorphism, rs9939609, with obesity was
      examined using the population of the Takahata study (n (M/F): 2,639 (1,168 /
      1,470); age: 63.0 +/- 10.2 years), a Japanese community-based study. The effects
      of lifestyle-related factors, including nutritional intake and physical
      activities, on the association were also examined. Body mass index (BMI) was
      significantly associated with the FTO gene polymorphism (p<0.001). A case-control
      association study of the FTO gene polymorphism with obesity using multiple
      logistic regression analysis showed a significant association of the genotype AA
      (odds ratio, 1.53 [95% confidential interval, 1.04-2.24]) after adjustment for
      age and gender. Analysis to examine the differences in lifestyle-related factors
      among the genotype groups showed a significant difference in the energy
      expenditure for moderate to high-intensity physical activity (PA) (> or = 3.0
      METs) (p=0.012) with a significant decrease toward the genotype AA (p=0.027). The
      effect of energy expenditure for moderate to high-intensity PA on the association
      of the polymorphism with obesity was then examined using study groups stratified
      based on the energy expenditure for moderate to high-intensity PA (Low-PA and
      High-PA). The BMI was significantly higher in the genotype AA in the Low-PA group
      (p=0.016) but not in the High-PA group (p=0.103). Furthermore, the genotype AA
      was significantly associated with obesity (odds ratio, 2.39 [95% confidential
      interval, 1.19-4.80]) in the Low-PA group but not in the High- PA group
      (p=0.650). The FTO gene, rs9939609, was associated with obesity, and the
      association was evident in subjects with low-PA, suggesting a PA-dependent
      association.

PMID- 20051648
TI  - First Japanese patient treated with parathyroid hormone peptide immunization for
      refractory hypercalcemia caused by metastatic parathyroid carcinoma.
AB  - Patients with unresectable parathyroid carcinoma develop severe hypercalcemia,
      bone fractures and renal failure, and become unresponsive to conventional
      treatments. It has been shown that successful induction of anti-parathyroid
      hormone (PTH) antibodies, using PTH peptide fragments for immunisation,
      normalized serum levels of calcium as well as improved clinical symptoms. Here,
      we report our experience of PTH immunization in a Japanese female suffering from
      refractory hypercalcemia and renal failure caused by unresectable metastatic
      parathyroid carcinoma. Upon immunization, there were apparent clinical responses
      including reduction of serum levels of Ca along with anti-PTH antibodies
      induction. Therefore, we concluded that PTH immunization was an effective
      treatment against hypercalcemia caused by metastatic parathyroid carcinomas that
      are unresponsive to conventional treatments.

PMID- 20051649
TI  - Reference ranges for serum IGF-1 and IGFBP-3 levels in Chinese children during
      childhood and adolescence.
AB  - Serum levels of insulin-like growth factor-1(IGF-1) and insulin-like growth
      factor binding protein-3(IGFBP-3) reflect endogenous growth hormone secretion,
      and serum IGF-1 and IGFBP-3 values should be ethnic-specific, thus we established
      the reference ranges for serum IGF-1 and IGFBP-3 in Chinese children aged 6-18 yr
      according to age, sex, puberty stage and BMI. The study was included 837 children
      (age 6-18 yr, 416 boys and 421 girls) from different schools in Daqing, Beijing
      and Shanghai. Serum IGF-1 and IGFBP-3 were determined by a chemiluminescent assay
      system (IMMULITE 1000). The results show that IGF1 reached peak levels at around
      13 yr in boys and 11 yr in girls while IGFBP-3 peaked at 14 yr in boys, and 11 yr
      in girls. Both IGF-1 and IGFBP-3 were at platform or decreased slightly after
      these ages. At each corresponding age, IGF-1 levels tended to be higher in boys
      compared to girls, while girls had higher IGFBP-3 levels than boys. A model for
      calculation of standard deviation scores of IGF-1 and IGFBP3 according to age,
      sex and pubertal stage was established. These normative data should facilitate
      child care, growth monitoring, clinical diagnosis and to follow up on GH
      treatment.

PMID- 20051651
TI  - Involvement of substance P and the neurokinin-1 receptor in radiation-induced
      hair loss in mice.
AB  - We investigated the involvement of substance P (SP) and the neurokinin-1 receptor
      (NK(1)R) in the development of radiation-induced hair loss in mice. A dose of 40
      Gy of gamma irradiation induced hair loss from the 10th to at least the 60th day
      after irradiation. A specific NK(1)R antagonist, CP-99,994, significantly delayed
      radiation-induced hair loss and reduced its severity. Furthermore, gamma
      irradiation induced the expression of preprotachykinin-A, a precursor protein of
      SP, mRNA in irradiated murine skin on the 10th and 30th days after irradiation.
      These results indicated that gamma irradiation-induced hair loss was mediated by
      SP via NK(1)R.

PMID- 20051652
TI  - Prostaglandin E2, an immunoactivator.
AB  - Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple
      sclerosis, and Crohn's disease, are intractable diseases to which novel
      therapeutics are highly demanded. Prostaglandin (PG) E(2) is the most
      ubiquitously produced PG with various actions. PGE(2) has been traditionally
      regarded as an immunosuppressant based on its inhibition of T cell activation in
      vitro. However, in vivo relevance of the immunosuppressant action of PGE(2) has
      remained obscure. Recently, several groups including ourselves have made
      unexpected findings that PGE(2) facilitates expansion of the Th17 subset of T
      helper cells of both human and mouse through elevation of cAMP via PGE receptors
      EP2 and EP4. We have further found that PGE(2) can induce and not suppress Th1
      differentiation under certain conditions, again, through EP2 and EP4. Given the
      putative roles of these Th subsets in immune diseases such as the above, these
      findings suggest that, on the contrary to the traditional view, PGE(2) functions
      as a mediator of immune inflammation. Consistently, administration of an EP4
      antagonist could suppress disease progression and development of antigen-specific
      Th17 cells in mice subjected to experimental allergic encephalomyelitis and
      contact hypersensitivity. In this perspective, we review these findings and
      discuss the prospect of EP4 antagonists as immunomodulatory drugs.

PMID- 20051653
TI  - Isolation and characterization of bovine intestinal subepithelial myofibroblasts.
AB  - Intestinal subepithelial myofibroblasts (ISMFs) are mesenchymal cells that exist
      under the epithelium of intestines. Primarily isolated ISMFs from rodents have
      been applied to experiments. However, due to the size of their intestines, the
      available cell number is limited. Thus, we attempted to isolate ISMFs from bovine
      colon as an alternative material. After detachment of smooth muscle and
      epithelial layers, colonic mucosa was explanted. After 2-week incubation, alpha
      SMA+ / vimentin+ / desmin(-) ISMFs were harvested and applied for experiments.
      First we examined the effect of cell passage on morphology and proliferation
      activity of bovine ISMFs. Although 3rd and 7th passage bovine ISMFs did not
      exhibit any changes, 11th passage ISMFs showed rounded enlarged shape and lost
      proliferation potential. On the contrary, rat ISMFs displayed the above senescent
      changes at earlier passage (passage 4). In intracellular Ca2+ concentration
      measurement, bioactive substances (0.3-1 microM ATP, 0.1-1 microM serotonin, 10
      100 nM endothelin-1, and 1-10 nM bradykinin) dose-dependently induced an increase
      in intracellular Ca2+ concentration in bovine ISMFs (passage 3 and 7). However,
      at passage 11, impairment in intracellular Ca2+ responses was observed. Thus,
      bovine ISMFs might be a novel useful tool with long life span and good cellular
      responses to investigate physiological/pathophysiological roles of ISMFs.

PMID- 20051654
TI  - Possible involvements of nuclear factor-kappa B and activator protein-1 in the
      tumor necrosis factor-alpha-induced upregulation of matrix metalloproteinase-12
      in human alveolar epithelial A549 cell line.
AB  - Matrix metalloproteinase-12 (MMP-12) has been suggested to play an important role
      in airway inflammatory diseases. Tumor necrosis factor-alpha (TNF-alpha) is known
      to cause an upregulation of MMP-12 via an activation of activator protein-1 (AP
      1) in monocytes. In the present study, we investigated the effect of TNF-alpha on
      the expressions of MMP-12 in airway epithelial cells, one of the sources of MMP
      12 in the airway, and its underlying mechanism. MMP-12 mRNA and protein
      expressions induced by TNF-alpha in the absence or presence of BMS-345541 (a
      selective IkappaB kinase inhibitor) or SP600125 [a selective c-Jun N-terminal
      kinase (JNK) inhibitor] were measured by quantitative real-time PCR and Western
      blotting, respectively. Furthermore, siRNAs for p65 and JNK2 were used to confirm
      the involvements of nuclear factor-kappaB (NF-kappaB) and AP-1 in the MMP-12 mRNA
      expression induced by TNF-alpha in A549 cells. Both MMP-12 mRNA and protein were
      upregulated by the treatment with TNF-alpha in time- and concentration-dependent
      manners. Both BMS-345541 and SP600125 inhibited the upregulation of MMP-12
      induced by TNF-alpha. Furthermore, both the depletion of p65 and JNK2 by siRNAs
      significantly attenuated the upregulation of MMP-12 induced by TNF-alpha. These
      findings suggest that both NF-kappaB and JNK / AP-1 pathways are important for
      the MMP-12 upregulation induced by TNF-alpha in A549 cells.

PMID- 20051655
TI  - A new chondrogenic differentiation initiator with the ability to up-regulate SOX
      trio expression.
AB  - During random screening for chondrogenic differentiation inducers, we found that
      Compound-1, 4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-1H-pyrazol-3-yl]benzene-1,3
      diol, initiated chondrogenic differentiation of the chondroprogenitor cell line
      ATDC5. Compound-1 initiated chondrogenic differentiation of the mesenchymal stem
      cell line C3H10T1/2 in regions where cell aggregates formed and simultaneously
      inhibited adipogenic differentiation. In C3H10T1/2 cells, Compound-1 increased
      the expression of Sry-related high-mobility-group box transcription factors L
      SOX5, SOX6, and SOX9 (SOX trio) more strongly than bone morphogenic protein (BMP)
      2. cAMP-dependent protein kinase (PKA) inhibitors suppressed Compound-1-dependent
      L-SOX5 and SOX6 up-regulation. PKA inhibitors also suppressed the up-regulation
      of aggrecan mRNA induced by Compound-1, indicating that increases in L-SOX5 and
      SOX6 mRNA, in which the PKA pathway participates, are involved in the mechanisms
      behind the action of Compound-1. On the other hand, the SOX6 and aggrecan gene
      expression, which were up-regulated by BMP-2, were not affected by the PKA
      inhibitor. Compound-1 induced chondrogenic differentiation of bone marrow stromal
      cells and recovered cartilage matrix production by primary chondrocytes, which
      had been decreased by interleukin-1beta. These results show the potential of
      Compound-1 to be a new cartilage repair agent for inducing chondrogenic
      differentiation via SOX trio up-regulation.

PMID- 20051656
TI  - Two non-steroidal anti-inflammatory drugs, niflumic acid and diclofenac, inhibit
      the human glutamate transporter EAAT1 through different mechanisms.
AB  - We investigated the effects of non-steroidal anti-inflammatory drugs on substrate
      induced currents of L-glutamate (L-Glu) transporter EAAT1 expressed in Xenopus
      laevis oocytes. Niflumic acid (NFA) and diclofenac inhibited L-Glu-induced
      current through EAAT1 in a non-competitive manner. NFA produced a leftward shift
      in reversal potential (E(rev)) of L-Glu-induced current and increased current
      amplitude at the potentials more negative than -100 mV. Diclofenac had no effects
      on E(rev) and inhibited the current amplitude to the same extent at all negative
      potentials. These results indicate that NFA and diclofenac inhibit the L-Glu
      induced EAAT1 current via different mechanisms.

PMID- 20051657
TI  - Pharmacological profile of the novel anti-inflammatory corticosteroid NS-126, a
      therapeutic agent for allergic rhinitis.
AB  - NS-126 (9-fluoro-11beta,17,21-trihydroxy-16alpha-methylpregna-1,4-diene-3,20
      dione 21-cyclohexanecarboxylate 17-cyclopropanecarboxylate) is a novel, highly
      lipophilic anti-inflammatory corticosteroid. We compared NS-126 and the widely
      used intranasal corticosteroid fluticasone propionate (FP) in a guinea-pig model
      of allergic rhinitis and a rat model of airway eosinophilia. In the allergic
      rhinitis model, NS-126 and FP reduced sneezing and nasal obstruction to similar
      extents. In the airway eosinophilia model, both compounds inhibited the
      infiltration of eosinophils into the bronchoalveolar lavage fluid, but the effect
      of NS-126 was longer-lasting than that of FP. In vitro, NS-126 showed lower
      affinity than FP for the glucocorticoid receptor and was a weaker inhibitor of
      Th(2) cytokine and chemokine production and mast-cell secretory responses. We
      also investigated DX-17-CPC, a metabolite of NS-126 generated in nasal tissue by
      carboxylesterase-catalyzed hydrolysis at the 17-position. DX-17-CPC showed
      greater affinity than NS-126 for the glucocorticoid receptor and was a stronger
      inhibitor of Th(2) cytokine and chemokine production and mast-cell secretory
      responses. The long duration of the anti-allergic effects of NS-126 may be
      explained by its high lipophilicity, while the strength of its anti-allergic
      effects may be explained by the generation of the active metabolite DX-17-CPC. NS
      126 is a long-acting intranasal corticosteroid and a promising therapeutic agent
      for allergic rhinitis.

PMID- 20051658
TI  - Effect of the C3a-receptor antagonist SB 290157 on anti-OVA polyclonal antibody
      induced arthritis.
AB  - It was investigated whether the C3a-receptor antagonist (C3aRA) SB 290157 was
      involved in the suppression of anti-OVA pAb-induced arthritis because it is well
      known that anaphylatoxin C3a plays a crucial role in the development of an
      effective inflammatory response during complement activation. Anti-OVA pAb
      induced arthritis was induced in DBA/1J mice by administration of anti-OVA pAb
      0.5 h prior to intra-articular (i.a.) injection of OVA (0 h). Two peaks of joint
      swelling were observed at 0.5 and 3 h. The role of C3aRA in arthritis was
      investigated by injection of SB 290157 at concentrations of 10 and 30 mg/kg at 0
      and 2 h. The antagonist was able to reduce joint swelling only at 3 h, and about
      50% inhibition of joint swelling was observed with the concentration of 30 mg/kg.
      The C3 level was significantly decreased at 3 h compared with naive mice showing
      complement consumption. Furthermore, the C3 activation was observed and increased
      corresponding to the graded concentration of anti-OVA pAb. The results also
      revealed that the C3aRA was able to reduce the expression of IL-1beta in synovial
      tissue. Taken together, the results suggested that C3aRA may be effective in the
      inhibition of arthritis.

PMID- 20051659
TI  - Intralesional pingyangmycin treatment for resistant plantar warts.
AB  - BACKGROUND: The diagnosis of viral warts is often straightforward, but their
      treatment is difficult and always takes a long time. Nowadays warts are usually
      treated with conventional methods including topical keratolytic agents,
      cryotherapy, electrosurgery and laser surgery. However, such treatments cause
      different complications, and the warts become recalcitrant. OBJECTIVE: To
      investigate the effect of intralesional pingyangmycin injection for resistant
      plantar warts. METHODS: From June 2006 to September 2008, we treated 66 patients
      with plantar warts by intralesional pingyangmycin injection after informed
      consent. RESULTS: The lesions of 58 patients cleared (87.88%) after up to 4
      treatments. The remaining 8 patients (12.12%) achieved partial clearance. No
      serious side effects were observed. CONCLUSION: Intralesional injection of
      pingyangmycin might be an effective, safe and generally well-tolerated treatment
      for plantar warts.

PMID- 20051660
TI  - Cardiac surgery in nonagenarians: single-centre series and review.
AB  - BACKGROUND: Cardiac surgery is widely believed to be an excessively high-risk
      intervention for very elderly patients with coronary artery or valvular disease.
      However, as life expectancy and the prospect of sustained quality of life into
      older age increase, this assumption should be challenged so that surgery is not
      denied to patients who may derive significant symptomatic benefit with acceptable
      levels of operative risk. OBJECTIVE: To evaluate outcomes from cardiac surgery in
      nonagenarian patients. DESIGN: Analysis of prospectively collected single-centre
      data and review of outcomes reported in the literature. RESULTS: Twenty-three
      patients (13 males) aged 90 years or more underwent open cardiac surgery between
      1998 and 2007. Four patients died within 30 days of surgery (surgical mortality
      17.4%) and all-cause in-hospital morbidity was 74%. Actuarial survival at 1 and 5
      years was estimated at 72 and 54%, respectively. Comparison of patients' survival
      against age-matched life tables for the English population found a standardised
      mortality ratio of 0.57 (95% CI: 0.24-0.99; one-sample log-rank test chi(2) =
      3.93; p < 0.05) representing a significant survival benefit associated with
      surgery. The majority of patients reported symptomatic improvement reflected by
      significant decreases in angina and dyspnoea scores. Six single-centre series of
      nonagenarians and 3 reviews from national databases in the US and UK were
      identified in the literature. Pooled surgical mortality was 12.7% (95% CI: 8.7
      17.3%) with no significant heterogeneity (chi(2) = 4.12; p = 0.77; I(2) = 0).
      CONCLUSION: Cardiac surgery in the elderly carries higher operative risk than in
      younger patients. However, in selected nonagenarians, surgery can be performed
      with acceptable morbidity and early mortality, and patients gain significant
      symptomatic relief and survival benefit.

PMID- 20051661
TI  - A revised activities of daily living/instrumental activities of daily living
      instrument increases interpretive power: theoretical application for functional
      tasks exercise.
AB  - BACKGROUND: As the number of adults in older age groups expands, difficulty
      performing usual activities of daily life is a rising health concern. A common
      exercise regimen employed to attenuate functional decline and disability has been
      resistance strength training. However, recent evidence suggests that functional
      tasks exercise may be more effective in preventing disability. OBJECTIVE:
      Activities of Daily Living (ADL) measures are one of the most widely used tools
      in gerontology, and yet the full sensitivity of these instruments is often not
      realized. The purpose of this study is to enhance the interpretive power of ADL
      by formally confirming a hierarchy of decline, assessing discriminatory power,
      and examining option characteristic curves. Theoretically, a revised ADL
      instrument can improve the efficacy of functional tasks training programs.
      METHODS: This was a cross-sectional study that employed Item Response Theory
      (IRT) to interpret ADL outcomes. Participants consisted of community-dwelling
      older adults (n=548, aged 79) living in Scotland. RESULTS: A Mokken scale with
      rho=0.77 was obtained, indicating good reliability, and satisfying the IRT
      assumption that a single unidimensional scale is present. The set H coefficient
      of 0.48 indicated that the scale may be ordered by decreasing difficulty, with
      the 'Cut your own toe-nails?' item being the most difficult and 'Tie a good knot
      in a piece of string?' being the least difficult. Discriminatory and option
      characteristic parameters revealed 'Get on a bus?' to be the task most closely
      related to the latent construct and that item options can be used to ascertain
      critical thresholds for prevention type strategies. CONCLUSIONS: Examining
      parameters relating to difficulty, discriminatory power, and option
      characteristics facilitated the identification of ADL/Instrumental ADL items that
      may serve to enhance functional task training in community-dwelling older adults.
      These analyses demonstrated that functional tasks have differing levels of
      discriminatory power, and that a task's discriminatory power is likely to change
      with varying levels of disability. This observation reinforces the notion that
      exercises based on functional tasks may differ significantly in their therapeutic
      effect. Lastly, this study was able to highlight statistically meaningful cut
      points relating to when older adults should begin 'prehabilitation'
      interventions.

PMID- 20051662
TI  - Update on procedure-related risks for prenatal diagnosis techniques.
AB  - INTRODUCTION: As a consequence of the introduction of effective screening
      methods, the number of invasive prenatal diagnostic procedures is steadily
      declining. The aim of this review is to summarize the risks related to these
      procedures. MATERIAL AND METHODS: Review of the literature. RESULTS: Data from
      randomised controlled trials as well as from systematic reviews and a large
      national registry study are consistent with a procedure-related miscarriage rate
      of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In
      single-center studies performance may be remarkably good due to very skilled
      operators, but these figures cannot be used for general counselling.
      Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage
      rate than CVS and mid-trimester amniocentesis, and also increased the risk of
      talipes equinovarus. Amniocentesis should therefore not be performed before 15 +
      0 weeks' gestation. CVS on the other hand should not be performed before 10
      weeks' gestation due to a possible increase in risk of limb reduction defects.
      DISCUSSION: Experienced operators have a higher success rate and a lower
      complication rate. The decreasing number of prenatal invasive procedures calls
      for quality assurance and monitoring of operators' performance.

PMID- 20051663
TI  - Clinical presentation and outcome of geriatric depression in subcortical ischemic
      vascular disease.
AB  - BACKGROUND: Vascular damage of frontal-subcortical circuits involved in mood
      regulation and cognition might be the main contributor to the pathogenesis of
      late-life depression, and it is linked to poor response to treatment. OBJECTIVE:
      To investigate the relationship between executive dysfunction and outcome of
      depressive symptoms among elderly patients with subcortical ischemic vascular
      disease. METHODS: Ninety-two elderly patients with white matter lesions (WMLs) or
      lacunar infarcts (LAs) on brain MRI and depressive symptomatology were
      consecutively recruited. Depression was rated with the Hamilton Depression Rating
      Scale (HDRS). Evaluation of executive functions by means of the Stroop color-word
      test was performed at entry of the study, and WMLs were categorized into mild,
      moderate or severe. Mood was reevaluated by means of HDRS after the 12th week of
      pharmacological treatment. RESULTS: Psychomotor retardation, difficulties at
      work, apathy, and lack of insight were the predominant symptoms. Fifty-six
      patients (62.8%) had a neuroradiological picture of WMLs, while the remaining 33
      (37.1%) had LAs. Executive dysfunctions significantly and independently predict
      poor outcome of depressive symptoms. Patients with the severest WMLs showed not
      only a greater executive dysfunction, but also a minor response to antidepressant
      treatment. CONCLUSION: This study supports the vascular depression hypothesis.
      WMLs are of crucial clinical relevance as they are linked with cognitive symptoms
      and poor antidepressant outcome.

PMID- 20051664
TI  - Isolated recurrent pleuritis revealing familial mediterranean Fever in adulthood.
AB  - Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease
      especially affecting populations of Mediterranean origin with an autosomal
      recessive inheritance. The cardinal manifestations consist of short febrile and
      painful attacks of peritonitis, arthritis and pleuritis developing during
      childhood. We report the case of a 26-year-old man of Tunisian descent who had
      febrile episodes of right-sided pleuritis without any extrathoracic complaints.
      Disappearance of attacks with one dose of colchicine (1 mg/day) strengthened the
      presumptive diagnosis of atypical FMF, which was further confirmed by genetic
      testing identifying the homozygous mutation M694I/M694I of the MEFV gene.

PMID- 20051665
TI  - On the perception of time.
AB  - In this article, we review scientific work and present new results on the
      perception of time, that is, on the feeling of time as perceived by individuals.
      The phenomenon of time being felt passing faster with growing age is well known,
      and there are numerous interesting studies to shed light on the question why this
      is so. Many of these are based on studies in psychology and social sciences.
      Others range from symptoms of the ageing process to related symptoms of
      decreasing memory capacities. Again other explanations, quite different in nature
      from the preceding ones, involve event intensities in the life of individuals.
      The relative decrease of interesting new events as one grows older is seen as an
      important factor contributing to the feeling that time is thinned out. The last
      type of possible explanations can be made more explicit in a mathematical model.
      Quantitative conclusions about the rate of decrease of the feeling of time can be
      drawn, and, interestingly, without restrictive assumptions. It is shown that
      under this model the feeling of time is thinned out at least logarithmically.
      Numerical constants will depend on specific hypotheses which we discuss but the
      lower-bound logarithmic character of the thinning-out phenomenon does not depend
      much on these. The presented model can be generalized in several ways. In
      particular we prove that there are, a priori, no logical incompatibilities in a
      model leading to the very same distribution of time perception for individuals
      with completely different pace and style of life. Our model is built to explain
      long-time perception. No claim is made that the feeling of time being thinned out
      is omnipresent for very individual. However, this is typically the case and we
      explain why.

PMID- 20051666
TI  - Comparative analysis of gene expression in rat liver tissue and monolayer- and
      spheroid-cultured hepatocytes.
AB  - A culture system with spherical multicellular aggregates (spheroids), which are
      formed by the rearrangement and compaction of cell aggregates, is reported to be
      more useful than the traditional monolayer culture system for the culture of
      primary hepatocytes. By performing real-time polymerase chain reaction, we
      analyzed the expression of genes encoding key molecules involved in liver
      specific functions, namely, cell adhesion molecules (integrin 3, cadherin 1 and
      connexin 32), transcription factors (hepatic nuclear factor 4alpha and
      CCAAT/enhancer-binding protein beta), protein and metabolic enzymes (albumin,
      glucose-6-phosphatase, tryptophan 2,3-dioxygenase, arginase 1 and cytochrome P450
      7A1) and transporters (organic anion transporting peptide 1, multidrug resistance
      associated protein 2 and bile salt export pump), in spheroids derived from rat
      hepatocytes. Further, we compared these expression levels with those in a
      hepatocyte monolayer and in liver tissue. Only the gene encoding glucose-6
      phosphatase (required for sugar metabolism) was expressed at a similar level in
      both the monolayer culture and liver tissue for 10 days of culture; the
      expression of all the other genes in the monolayer culture either rapidly
      decreased or completely disappeared as the culture duration increased. Although
      the expression levels of all the genes in the spheroids tended to decrease
      gradually with culture time, they were consistently higher than those in the
      monolayer culture for at least 10 days of culture. These results suggest that
      hepatocyte spheroids acquire intercellular organization and largely maintain many
      intercellular metabolic functions. Thus, the hepatocyte spheroid culture system
      seems to be promising for various in vitro cell-based assays.

PMID- 20051667
TI  - Vasoactive intestinal peptide improves the survival and development of caprine
      preantral follicles after in vitro tissue culture.
AB  - The aim of this study was to evaluate the effect of vasoactive intestinal peptide
      (VIP)on the survival, activation and growth of goat preantral follicles after in
      vitro culture. The ovarian cortex was divided into small pieces and one fragment
      was immediately fixed (control). The remaining fragments were cultured in vitro
      for 1 or 7 days at 39 degrees C and 5% CO(2), in supplemented minimum essential
      medium (MEM(+)) with or without different concentrations of VIP (1, 10, 50, 100
      or 200 ng/ml). Noncultured (fresh control) and cultured ovarian fragments were
      processed for histological analysis and transmission electron microscopy.
      Follicles were classified as primordial or developing, and as normal or
      degenerated. Our findings indicate that when compared with control, addition of
      all concentrations of VIP except 200 ng/ml resulted in similar percentages of
      normal preantral follicles after 1 and 7 days of culture. Culture of ovarian
      cortex tissue for 1 and 7 days increased the percentage of follicular activation
      in all treatments when compared with control, except with 1 ng/ml of VIP after 1
      day. However, no difference was observed between VIP-treated and MEM(+)-treated
      follicles. In addition, after 7 days of culture, the highest follicular and
      oocyte diameters were observed in follicles cultured with 10 ng/ml VIP relative
      to MEM(+) alone. Transmission electron microscopy showed ultrastructural
      integrity of follicles after 7 days of culture in 10 ng/ml VIP. In conclusion,
      this study demonstrates that VIP maintains follicular integrity and stimulates
      caprine preantral follicle growth.

PMID- 20051668
TI  - Unique modulation of cadherin expression pattern during posterior frontal cranial
      suture development and closure.
AB  - Cranial suture development involves coordinated expression of multiple genes and
      tissue contribution from neural crest cells and paraxial mesoderm for timely
      sutural morphogenesis. Transcription factors, growth factors, and neural crest
      determinant genes play critical roles in calvarial growth ensuring normal
      development of the underlying brain. In vitro studies have implicated cell-cell
      adhesion molecules as a driving force behind suture closure. We performed cDNA
      microarray to study differential expression of adhesion molecules during the
      timing of suture closure in a mouse model where only the posterior frontal (PF)
      suture closes. Our results indicate increased expression of E-cadherin during the
      period of PF suture closure. Quantitative RT-PCR analysis of E- and N-cadherin in
      PF closing suture revealed a biphasic expression of N-cadherin, the first phase
      coinciding with cellular condensation preceding chondrogenesis followed by a
      second phase coinciding with E-cadherin co-expression and suture closure.
      Furthermore, expression analysis of the N-cadherin and E-cadherin transcriptional
      repressors Wnt7a and Snail indicate a specific temporal regulation of these
      genes, suggesting their potential role as regulators of both E- and N-cadherin
      during the PF suture development and closure. Finally, given the in vitro
      evidence of fibroblast growth factor (FGF)-2 as a potential regulator of E- and N
      cadherin we investigated the expression of E-cadherin during PF suture closure in
      Fgf-2 deficient mice. In contrast to in vitrodata previously reported, E-cadherin
      expression is normal in these animals, and PF suture closure occurs properly,
      probably due to potential redundancy of FGF ligands ensuring normal temporal
      expression of E-cadherin and PF suture closure.

PMID- 20051669
TI  - Educating underserved Latino communities about family health history using lay
      health advisors.
AB  - BACKGROUND: Family health history (FHH) is a tool used to inform individuals
      about inherited disease risk. Due to their disproportionate morbidity and
      mortality from some common chronic diseases, U.S. Latinos are an important
      audience for FHH information. This study examined the effects of a culturally
      tailored intervention led by lay health advisors (LHAs) in delivering information
      about FHH on participants' intentions, self-efficacy, and conceptual knowledge.
      METHODS: 474 Spanish-speaking Latino participants were enrolled in the study.
      Individuals in the intervention group participated in a single group educational
      session using discussion and interactive activities to build skills for
      discussing FHH with one's family members and doctor, while individuals in the
      comparison group had a brochure read aloud to them. Pre- and post-test
      questionnaires were verbally administered. RESULTS: Primary dependent variables
      were intentions and self-efficacy to discuss FHH with family members and doctors;
      these increased in both groups. Multivariate analyses demonstrated that the
      intervention led to a significantly greater increase in self-efficacy to discuss
      FHH with family members (p = 0.03). LHA participants were also more than twice as
      likely (OR = 2.6, 95% CI = 1.3-5.0) to correctly understand the purpose of a FHH
      and found FHH information more useful (p < 0.0001). CONCLUSIONS: A communication
      intervention delivered by LHAs shows promise as an effective means of educating
      underserved Spanish-speaking Latinos about the importance of FHH for disease
      prevention. Such community-based approaches can help to close knowledge and
      skills gaps about FHH and increase confidence in using this information to
      improve the health of those most at risk.

PMID- 20051670
TI  - Interleukin 10 gene polymorphisms and development of post kala-azar dermal
      leishmaniasis in a selected sudanese population.
AB  - BACKGROUND: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of
      disease that develops at variable times after individuals have received treatment
      for clinical visceral leishmaniasis (VL). The study aimed to investigate the
      possible role of interleukin 10 (IL-10) and development of PKDL. METHODS: 77
      families composed of 41 complete case-parent trios and 36 case-parent pairs from
      the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: 
      1082A/G, -819C/T and -592C/A. RESULTS: Single point analysis using the
      transmission disequilibrium test showed no evidence of association between any of
      these IL10 promoter single nucleotide polymorphisms (SNPs) and development of
      PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance
      between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053).
      Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese
      population. Allele frequencies for the 3 SNPs differed significantly in Sudan
      compared to other African (Gambian, Malawian, YRI) populations. CONCLUSION: There
      is no evidence for an association between 3 SNPs in the IL10 gene promoter and
      susceptibility to PKDL in the Masalit ethnic group in Sudan, although some
      evidence for haplotype association was observed.

PMID- 20051671
TI  - Molecular cytogenetics of the california condor: evolutionary and conservation
      implications.
AB  - Evolutionary cytogenetic comparisons involved 5 species of birds (California
      condor, chicken, zebra finch, collared flycatcher and black stork) belonging to
      divergent taxonomic orders. Seventy-four clones from a condor BAC library
      containing 80 genes were mapped to condor chromosomes using FISH, and 15 clones
      containing 16 genes were mapped to the stork Z chromosome. Maps for chicken and
      finch were derived from genome sequence databases, and that for flycatcher from
      the published literature. Gene content and gene order were highly conserved when
      individual condor, chicken, and zebra finch autosomes were compared, confirming
      that these species largely retain karyotypes close to the ancestral condition for
      neognathous birds. However, several differences were noted: zebra finch
      chromosomes 1 and 1A are homologous to condor and chicken chromosomes 1, the
      CHUNK1 gene appears to have transposed on condor chromosome 1, condor chromosomes
      4 and 9 and zebra finch chromosomes 4 and 4A are homologous to chicken chromosome
      arms 4q and 4p, and novel inversions on chromosomes 4, 12 and 13 were found.
      Condor and stork Z chromosome gene orders are collinear and differentiated by a
      series of inversions/transpositions when compared to chicken, zebra finch, or
      flycatcher; phylogenetic analyses suggest independent rearrangement along the
      chicken, finch, and flycatcher lineages.

PMID- 20051672
TI  - Sex allocation and sex determination in squamate reptiles.
AB  - Reptiles possess a wide variety of sex determining mechanisms, more so than any
      other vertebrate group. They offer outstanding opportunities to understand the
      evolutionary transitions between modes of sex determination. In this review, we
      argue that sex allocation theory is fundamental for understanding the selective
      causes of such shifts. Whether selection for biased sex allocation actually
      results in evolutionary shifts in sex determination depends on the overall
      strength, direction and consistency of selection and to what extent existing
      reproductive systems can establish novel links between factors causing sex
      specific fitness and mechanisms of sex determination. Perhaps one of the most
      exciting advances in recent years has been the phylogenetically diverse range in
      reptile taxa that form the basis of research on the evolution of sex
      determination. The traditional use of long-lived oviparous species (especially
      turtles and crocodiles) is now expanded to include a range of short-lived taxa
      that exhibit both genetic sex determination and environment-/temperature
      dependent sex determination (particularly agamid lizards), as well as a greater
      emphasis on viviparous species. If selection on differential sex allocation is a
      key selective pressure for the evolution of sex-determining mechanisms, these
      taxa will provide considerable insights into the integrated fields of sex
      allocation biology and sex determination.

PMID- 20051673
TI  - Translational research in cancer genetics: the road less traveled.
AB  - Gene discoveries in cancer have the potential for clinical and public health
      applications. To take advantage of such discoveries, a translational research
      agenda is needed to take discoveries from the bench to population health impact.
      To assess the current status of translational research in cancer genetics, we
      analyzed the extramural grant portfolio of the National Cancer Institute (NCI)
      from Fiscal Year 2007, as well as the cancer genetic research articles published
      in 2007. We classified both funded grants and publications as follows: T0 as
      discovery research; T1 as research to develop a candidate health application
      (e.g., test or therapy); T2 as research that evaluates a candidate application
      and develops evidence-based recommendations; T3 as research that assesses how to
      integrate an evidence-based recommendation into cancer care and prevention; and
      T4 as research that assesses health outcomes and population impact. We found that
      1.8% of the grant portfolio and 0.6% of the published literature was T2 research
      or beyond. In addition to discovery research in cancer genetics, a translational
      research infrastructure is urgently needed to methodically evaluate and translate
      gene discoveries for cancer care and prevention.

PMID- 20051674
TI  - Guiding policy decisions for genetic screening: developing a systematic and
      transparent approach.
AB  - With the ever-widening gap between what is technologically possible and services
      available, jurisdictions around the world are faced with complex decisions
      regarding the introduction and expansion of genetic screening programs. A series
      of literature reviews and consultations with stakeholders and experts led to the
      development of a decision support guide for genetic screening policy-making. This
      involved establishing a preliminary list of core criteria synthesized from the
      growing literature on genetic screening, which was then transformed through a
      series of consultations into a more elaborate decision guide. Although certain
      perennial challenges in genetic screening policy-making remain, the decision
      support guide aims to promote a fair and evidence-informed process that makes
      explicit the ethical dilemmas often inherent to such policy decisions.

PMID- 20051675
TI  - Early expression of the androgen receptor in the Sertoli cells of a marsupial
      coincides with downregulation of anti-Mullerian hormone at the time of urogenital
      virilization.
AB  - Anti-Mullerian hormone (AMH), responsible for the regression of Mullerian ducts,
      is strongly expressed by eutherian fetal and postnatal Sertoli cells. Both AMH
      and testosterone levels are high during the period of fetal reproductive tract
      virilization which occurs largely in utero in eutherian mammals. Taking advantage
      of the fact that differentiation of the urogenital tract occurs after birth in
      marsupials, we studied the ontogeny and regulation of AMH in the tammar wallaby
      testis and related it to the expression of the androgen receptor in Sertoli
      cells. Testicular AMH expression was high between days 10-30 post partum, then
      fell to basal levels by day 60 and remained low until day 90, the oldest age
      examined. AMH expression was repressed by treatment of male pouch young with the
      potent androgen androstanediol. Thus, in the tammar, AMH expression decreases in
      response to androgen at the time of initial urogenital masculinization, in
      contrast to the situation in humans in which AMH is repressed by testosterone
      only at the time of puberty. The difference might be explained by the timing of
      androgen receptor expression which appears in tammar Sertoli cells at around day
      40 of pouch life but only at a later developmental stage in eutherians.

PMID- 20051676
TI  - A molecular diagnostic test for persistent Mullerian duct syndrome in miniature
      schnauzer dogs.
AB  - In persistent Mullerian duct syndrome (PMDS), Mullerian ducts fail to regress in
      males during sexual differentiation. In the canine miniature schnauzer model,
      PMDS is caused by a C to T transition in exon 3 of the Mullerian inhibiting
      substance type II receptor (MISRII), which introduces a DdeI restriction site.
      Here we report a molecular diagnostic test for PMDS in the miniature schnauzer to
      identify affected dogs and carriers. As our test results suggest that the
      mutation is identical by descent in affected dogs of this breed, the test could
      be used to eliminate this mutation from the miniature schnauzer breed worldwide.

PMID- 20051677
TI  - A girl with tomboy behavior: lesson from misdiagnosis in a baby with ambiguous
      genitalia.
AB  - 5alpha-Reductase-2 deficiency is a rare 46,XY disorder of sex differentiation
      caused by mutations in the 5alpha-reductase type 2 gene. It presents at birth
      with variable degree of undervirilization. Here, a baby with 5alpha-reductase-2
      deficiency and misdiagnosis of complete androgen insensitivity syndrome, female
      sex assignment and early gonadectomy is described. During primary school, the
      girl developed tomboy behavior. Molecular analysis demonstrated compound
      heterozygosity for 5alpha-reductase type 2 gene mutations (exon 2: Q126R; exon 4:
      H230P). This child underlines the need for adequate endocrine and genetic testing
      for a definite diagnosis before gender is assigned in children with ambiguous
      genitalia and surgical interventions are carried out. Inadequate work-up may
      result in inappropriate gender assignment in infancy with possible inferences on
      outcome.

PMID- 20051678
TI  - A comparative study of proliferation and hepatic differentiation of human adipose
      derived stem cells.
AB  - Human adipose-derived stem cells possess a lot of stem cell characteristics, so
      they may be considered a source of stem cell population. On the basis of that, we
      have investigated the hepatic potential of adipose-derived stem cells, obtained
      from liposuction, following two differentiation protocols. In the first
      procedure, medium was supplemented with epidermal growth factor (EGF), basic
      fibroblast growth factor, hepatocyte growth factor (HGF) and nicotinamide; the
      second involved the addition of factors such as dexametasone, EGF, insulin
      transferrin-sodium selenite, HGF, dimethyl sulfoxide and oncostatin. In parallel,
      we carried out our study in the Hep G2 cell line, as human hepatic differentiated
      in vitro model. Immunocytochemical analysis and RT-PCR were performed using
      hepatic markers to evaluate cell differentiation. DNA content, MTT test and
      carboxyl fluorescein succinimidyl ester staining were carried out to evaluate
      cell proliferation. We reported the evidence of basal hepatic marker in
      undifferentiated adipose-derived stem cells, which confirmed their multipotency.
      A strong expression of albumin and alpha-fetoprotein was observed in hepatic
      induced adipose-derived stem cells following both differentiation procedures.
      Morphological aspects of the two types of hepatic adipose-derived stem cells were
      alike. Proliferation index suggested that the first differentiation procedure
      promoted better growth than the second. These preliminary findings suggest
      adipose-derived stem cells may be induced into hepatic lineage, and the most
      significant difference between the two standard differentiation procedures
      concerns proliferation rate. This aspect is to be considered when adipose-derived
      stem cells are employed in research and clinical studies.

PMID- 20051679
TI  - Cryopreservation of autologous bone grafts: an experimental study on a sheep
      animal model.
AB  - A sheep animal model was used to investigate the clinical behavior of autologous
      bone transplants after cryopreservation. The aim of the present study was to
      compare fresh, cryopreserved and deep-frozen bone transplants in terms of their
      osseointegration. We used a serum-free cryopreservation protocol with DMSO as
      cryoprotectant for the bone transplants, which were harvested from the iliac
      crest of the sheep. The bicortical iliac bone grafts were either cryopreserved or
      immediately frozen to -80 degrees C for 4 weeks. Four, 8, 12 and 16 weeks after
      the autologous transplantation of the cryopreserved, fresh or deep-frozen bone
      transplants to the contralateral iliac crest, the animals were sacrificed and the
      bone specimens were evaluated clinically, by staining for hematoxylin/eosin and
      for tartrate-resistant acid phosphatase, by quantified computed tomography,
      immunohistochemistry (Ki67) and polychrome sequential labeling. The best results
      were obtained for the fresh specimens with 83% bone healing compared with 75%
      (cryopreserved bone) and 50% (deep frozen bone). All parameters indicate that
      bone formation and remodeling processes take place in fresh and cryopreserved
      transplants. The deep-frozen specimens displayed no fluorochrome uptake in the
      sequential labeling. These findings indicate that osseointegration of the fresh
      transplants was the most successful and that osteogenic effects in fresh and
      cryopreserved transplants are located in the surface area, whereas only the
      osteoconductive effects are important in the center of the transplants. Thus,
      cryopreservation is a useful method for the clinical routine because it keeps the
      osteogenic cells viable, making it superior to deep freezing of abundant bone.

PMID- 20051680
TI  - Tracheobronchitis caused by methicillin-resistant Staphylococcus aureus as a
      cause of chronic wheezing in a non-ventilated adult patient with
      tracheobronchomalacia.
AB  - Bacterial tracheobronchitis is an extremely rare entity, which was long
      considered to be a pediatric disease. We report the case of a 65-year-old woman
      who presented with persistent wheezing, worsening productive cough and sore
      throat. Computed tomography of the chest revealed the presence of tracheomalacia,
      confirmed at bronchoscopy. The presence of purulent exudate, coating the trachea
      and main bronchi, was consistent with bacterial tracheobronchitis. Culture of the
      tracheal aspirates grew methicillin-resistant Staphylococcus aureus (MRSA). As
      the patient was afebrile and not systemically ill, the clinical picture was
      consistent with exudative tracheobronchitis. To our knowledge, this is the first
      case of MRSA exudative tracheobronchitis and tracheomalacia in a non-ventilated
      adult. Other adult cases of bacterial tracheobronchitis and MRSA
      tracheobronchitis in mechanically ventilated patients reported in the literature
      are also reviewed.Physicians should be aware of the diagnosis of tracheomalacia
      in adults, which can masquerade as persistent asthma and may be associated with
      the development of serious infections including MRSA tracheobronchitis.

PMID- 20051681
TI  - Deficient histone acetylation in acute leukemia and the correction by an
      isothiocyanate.
AB  - OBJECTIVE: Since histone hypoacetylation due to excess histone deacetylases
      (HDACs) has been associated with transcriptional repression in leukemia, we aimed
      to determine deficient histone acetylation in patients with acute leukemia and
      the effect of its correction by an isothiocyanate. METHODS: The acetylation
      status of histones H3 and H4 in cells from patients with untreated acute leukemia
      was determined by Western blot. Deficient histone acetylation was analyzed in
      relation to the disease state. Bone marrow cells from 10 patients with acute
      myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to
      evaluate correction of the deficiency. RESULTS: Acetylation of histones H3 and H4
      was virtually undetectable or significantly lower in acute leukemia. This
      deficiency was consistent among all the patients examined. Histone acetylation
      was up-regulated in the presence of PHI, revealing an excess of deacetylation
      activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was
      able to correct the deficiency. CONCLUSIONS: Deficient histone acetylation may
      represent an aberration at the epigenetic level in acute leukemia. PHI might
      represent a target for correcting deficient acetylation, and potential epigenetic
      regulators for preventing the progression of leukemia.

PMID- 20051682
TI  - Which role for rituximab in hairy cell leukemia? Reflections on six cases.
AB  - Hairy cell leukemia (HCL) is a rare, chronic, B-cell, lymphoproliferative
      disorder. Treatment has been revolutionized by the advent of interferon (IFN)
      alpha and purine analogs (PA). First-line therapy with PA yields complete
      response rates of 75-100%, with many long-lasting remissions. In the event of
      profound neutropenia and/or infectious complications, a short sequence of IFN
      alpha may precede PA treatment. Because of the excellent results achieved with PA
      therapy, the potential role of rituximab (an anti-CD20 monoclonal antibody that
      is highly effective against most B-cell lymphomas) in HCL has yet to be
      elucidated. Six HCL cases treated with rituximab are reported herein with a view
      to elucidating the potential role of the drug in HCL. The indications essentially
      consist of relapsing or refractory disease, avoiding the cumulative toxicity of
      PA, consolidation therapy in order to eradicate minimal residual disease, and
      first-line therapy for patients with contraindications to PA and IFN-alpha.

PMID- 20051683
TI  - Variations in compliance with recommendations and types of meat/seafood/eggs
      according to sociodemographic and socioeconomic categories.
AB  - BACKGROUND/AIMS: Strategic goals for meat/seafood/egg consumption include variety
      and adherence to recommendations while avoiding excessive intake. The aim of this
      study was to investigate their association with sociodemographic and -economic
      characteristics in a general population of French adults. METHODS: Dietary intake
      was assessed using at least six 24-hour dietary records collected during a 2-year
      period from 4,574 subjects aged 45-60 years who participated in the SU.VI.MAX
      cohort study from 1995 to 1997. Compliance with the meat/seafood/egg (1-2
      servings/day) and the specific seafood (> or =2 servings/week) recommendations,
      variety and daily costs were compared across sociodemographic and -economic
      categories using logistic regression and covariance analyses. RESULTS: Compliance
      with the sea- food recommendation was associated with older age (p(trend)<
      0.0001), higher education level (p(trend) = 0.0002) and higher occupational
      category (p = 0.007). The variety of meat/seafood/egg intake was positively
      correlated with higher occupational category (p = 0.02) and not living alone (p =
      0.01). The meat/seafood/egg budget spent on white meat was higher for younger
      subjects (p(trend) = 0.007) with a lower education level (p(trend) = 0.001) and
      occupational category (p = 0.0006). In contrast, fish costs increased with age
      (p(trend) = 0.002) and education level (p(trend) = 0.0002), while red meat costs
      were positively correlated with higher occupational category (p = 0.02).
      CONCLUSIONS: Compliance with recommendations, variety and types of
      meat/seafood/eggs differed across sociodemographic and -economic categories.

PMID- 20051684
TI  - The independent evolution of the enlargement of the principal sensory nucleus of
      the trigeminal nerve in three different groups of birds.
AB  - In vertebrates, sensory specializations are usually correlated with increases in
      the brain areas associated with that specialization. This correlation is called
      the 'principle of proper mass' whereby the size of a neural structure is a
      reflection of the complexity of the behavior that it subserves. In recent years,
      several comparative studies have revealed examples of this principle in the
      visual and auditory system of birds, but somatosensory specializations have
      largely been ignored. Many species rely heavily on tactile information during
      feeding. Input from the beak, tongue and face, conveyed via the trigeminal,
      facial, glossopharyngeal and hypoglossal nerves, is first processed in the brain
      by the principal sensory nucleus of the trigeminal nerve (PrV) in the brainstem.
      Previous studies report that PrV is enlarged in some species that rely heavily on
      tactile input when feeding, but no extensive comparative studies have been
      performed. In this study, we assessed the volume of PrV in 73 species of birds to
      present a detailed analysis of the relative size variation of PrV using both
      conventional and phylogenetically based statistics. Overall, our results indicate
      that three distinct groups of birds have a hypertrophied PrV: waterfowl
      (Anseriformes), beak-probing shorebirds (Charadriiformes), and parrots
      (Psittaciformes). These three groups have different sensory requirements from the
      orofacial region. For example, beak-probing shorebirds use pressure information
      from the tip of the beak to find buried prey in soft substrates, whereas
      waterfowl, especially filter-feeding ducks, use information from the beak,
      palate, and tongue when feeding. Parrots likely require increased sensitivity in
      the tongue to manipulate food items. Thus, despite all sharing an enlarged PrV
      and feeding behaviors dependent on tactile input, each group has different
      requirements that have led to the independent evolution of a large PrV.

PMID- 20051685
TI  - A simple and accurate method for estimating the brain volume of birds: possible
      application in paleoneurology.
AB  - Brain volume provides useful information for a discussion of the behavior and
      cognition of animals. Obtaining accurate brain volume from extinct species is
      difficult, however, because fossils are often partly or largely broken. The
      purpose of this study was to estimate the brain volumes of birds using scant
      osteological information. Brain volumes were calculated from magnetic resonance
      or computed tomography images of bird heads from 27 species representing 12
      orders. Correlations between brain volume and maximum brain width, length, and
      height were assessed using multiple regression analysis and correlation analysis.
      Brain volume and maximum brain width show a strong linear correlation. Thus, in
      the extant Neornithes (modern birds), it is possible to estimate brain volume
      accurately from the maximum brain width using a standard line. We also used this
      method to calculate the brain volumes of fossil species to assess whether it can
      be used for extinct species. The brain volume values estimated by this method fit
      satisfactorily with the reported values in extinct Neornithes, suggesting that
      the method is applicable not only for extant, but also for extinct Neornithes and
      might be a powerful tool to obtain information not previously available from
      fossil specimens.

PMID- 20051686
TI  - Beta-blockers in acute coronary syndrome.

PMID- 20051687
TI  - Familial Creutzfeldt-Jakob disease with a V180I mutation: comparative analysis
      with pathological findings and diffusion-weighted images.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) has been reported to be a useful
      technique for diagnosing Creutzfeldt-Jakob disease (CJD). The present study
      reported DWI results in cases of familial CJD with a V180I mutation (CJD180) in
      the prion protein gene as well as neurological findings. METHODS: A retrospective
      analysis of 3 patients with V180I was performed. Cerebrospinal fluid (CSF)
      analysis, brain MRI, single-photon emission computed tomography (SPECT), and
      magnetic resonance spectroscopy (MRS) were included. CSF was analyzed for
      biochemical markers, and each patient underwent brain MRI, SPECT, and MRS
      analysis. A brain biopsy from the frontal cortex, which corresponded to the area
      of increased DWI signals, was utilized for neuropathological analysis. RESULTS:
      CSF analysis results revealed elevated total tau protein and the absence of 14-3
      3 protein, as well as decreased concentrations of neuron-specific enolase, S100
      protein, and prostaglandin E(2). All patients presented with unique MRI features.
      Brain biopsy showed severe spongiform morphology, but comparatively preserved
      neurons and mild astrocytic gliosis. Accumulations of PrP(Sc) were not detected
      using the 3F4 antibody, and microglial activation was subtle. SPECT revealed
      hypoperfusion throughout both hemispheres. MRS revealed a reduced N-acetyl
      aspartate/creatine ratio. CONCLUSION: Results from this study suggested that
      increased DWI signals could reflect severe spongiform changes in CJD180 patients.

PMID- 20051688
TI  - Coexistence between carotid artery stenosis and colorectal adenomatous polyps in
      middle-aged men.
AB  - BACKGROUND: Colorectal neoplasia and cardiovascular disease appear to share
      common risk factors. This study aimed to investigate the association between the
      thickness of the intima-media complex (IMT) or carotid artery stenosis (CAS) on
      carotid artery ultrasonography and the presence of colorectal adenomas in middle
      aged asymptomatic men. METHODS: This study was conducted among 1,877 asymptomatic
      male subjects, 40-59 years, who underwent both carotid artery ultrasonography and
      colonoscopy for routine health examination. Clinical information was collected
      from a standardized questionnaire, physical examination and blood tests. RESULTS:
      The prevalence of overall colorectal adenomatous polyps (APs) was 31.4%
      (591/1,877). The subjects were divided into two groups according to the presence
      of APs in the colorectum. The prevalence of IMT >or=10 mm was significantly
      higher in the subjects with CAS than in those without CAS (10.1 vs. 0.7%, p <
      0.001). CAS was more prevalent in the AP-positive group than in the AP-negative
      group (40.5 vs. 30.2%, p = 0.001). Moreover, CAS was more prevalent in the
      advanced AP-positive group than in the advanced AP-negative group (15.2 vs. 8.2%,
      p = 0.048). CONCLUSION: This study suggests that there is a relationship between
      colorectal AP and CAS, probably due to common risk factors.

PMID- 20051689
TI  - Oxaliplatin for chemotherapeutic treatment and prevention of experimental
      peritoneal carcinomatosis in rats comparing the intraperitoneal and intravenous
      application mode.
AB  - BACKGROUND: The occurrence of peritoneal carcinomatosis after resection of
      colorectal carcinoma is still a major concern. In this study, we tested the
      cytostatic agent oxaliplatin delivered intraperitoneally and intravenously to
      prove whether it can significantly reduce intraperitoneal tumor growth. METHODS:
      Peritoneal tumor growth was experimentally induced with transfer of CC-531 colon
      cancer cells (5 x 10(6)) to the peritoneal surface of rats via laparotomy.
      Oxaliplatin was delivered either intraperitoneally or intravenously. In group A,
      oxaliplatin was administered directly after tumor cell transfer. While
      oxaliplatin was applied in group B on days 5, 10, and 15 after tumor cell
      implantation, in group C, it was administered on days 10, 15 and 20. The rats
      were sacrificed on day 30 after tumor cell transfer. Tumor weight, relative
      increase in tumor mass, volume of malignant ascites and the number of tumor nodes
      were determined. RESULTS: Oxaliplatin significantly inhibited tumor growth after
      direct (group A) and early postoperative application (group B) via the
      intraperitoneal route. The late postoperative administration of oxaliplatin
      (group C) did not cause a significant effect on peritoneal tumor growth as it did
      with the intravenous application mode in groups A, B, and C. CONCLUSIONS: In this
      experimental model, oxaliplatin was highly effective against intraperitoneal
      tumor spread but only with the intraperitoneal application route. Other
      cytostatic agents with different effector mechanisms should be combined with
      oxaliplatin to further increase the therapeutic efficacy of the favorable
      intraperitoneal treatment in subsequent studies testing, in addition, the effects
      on wound and anastomosis healing.

PMID- 20051690
TI  - A case study of a pregnant patient with a congenital heart block accompanied by
      left isomerism and uncontrolled type 2 diabetes who was treated successfully with
      ritodrine.
AB  - We present a case study of a patient with a congenital heart block associated
      with a left isomerism that was diagnosed during the 26th week of gestation. The
      mother had type 2 diabetes mellitus that was difficult to control during the
      early stages of the pregnancy. A fetal echocardiogram revealed an
      atrioventricular dissociation, with an atrial rate of 120 bpm and a ventricular
      rate of 55 bpm. Subsequent examinations also revealed a left isomerism in the
      fetus. To increase the fetal heart rate, a continuous intravenous infusion of
      ritodrine was administered. The fetal ventricular rate rapidly increased to 65
      bpm. The pregnancy successfully continued until term and a female infant weighing
      3,182 g was born via a cesarean section. A subsequent surgery was performed to
      provide the infant with a permanent cardiac pacemaker, and notably, the child is
      now 4 months of age and her growth has been within the normal range.

PMID- 20051691
TI  - Effect of follicular fluid oxidative stress on meiotic spindle formation in
      infertile women with polycystic ovarian syndrome.
AB  - BACKGROUND: The effect of follicular fluid (FF) oxidative stress (OS) on meiotic
      spindle (MS) formation in oocytes and subsequent outcome in women with polycystic
      ovarian syndrome (PCOS) are evaluated in this study. METHODS: 326 oocytes from 35
      PCOS women (group A) and 208 oocytes from 32 women with tubal infertility (group
      B) were visualized for MS using PolScope. FF was analyzed for OS markers
      including reactive oxygen species (ROS), lipid peroxidation and total antioxidant
      capacity (TAC). Group A was further classified into groups A1 and A2, and group B
      into groups B1 and B2 depending upon the presence or absence of MS, respectively.
      RESULTS: MS formation was absent in a significantly higher number of oocytes in
      group A compared to group B (p <or= 0.05). OS markers were significantly higher
      in group A compared to group B (p <or= 0.05). Fertilization rate, number of good
      quality embryos and clinical pregnancy rates were higher in group B compared to
      group A, though not statistically significant. FF ROS was significantly higher
      and TAC significantly lower in groups A2 and B2 compared to groups A1 and B1 (p <
      0.001). CONCLUSION: The presence of MS and oocyte maturation in PCOS women showed
      a positive correlation with low levels of OS.

PMID- 20051692
TI  - Treatment of endometriosis with transvaginal ultrasound-guided drainage and
      recombinant interleukin-2 left in the cysts: a third clinical trial.
AB  - BACKGROUND: To analyze the therapeutic results of recombinant interleukin-2 (rIL
      2) left in the cysts after transvaginal ultrasound (US)-guided drainage of
      endometriomas as an alternative to surgery. METHODS: Prospective and randomized
      clinical trial. A total of 25 consecutive patients were included. Two
      transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were
      left in the aspirated cysts once (group I) or both (group II) times according to
      randomization. MAIN OUTCOME MEASURES: Clinical results, prevented surgeries, and
      recurrences. RESULTS: Results were moderate or good in only 16% of subjects at 3
      months and in 33% of subjects at 6 months after treatment in group I; these
      numbers were 66 and 33%, respectively, in group II. Differences were not
      statistically significant. However, the evolution of symptoms, endometriomas, and
      CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor
      control of the clinical manifestations. After 1 year, 20% (group I) and 73%
      (group II) of patients had to be operated; after 2 years, these numbers were 55
      and 82%, respectively. CONCLUSIONS: Treatment of endometriomas with transvaginal
      US-guided drainage and rIL-2 left in the cysts, without using endometrial
      suppressive therapy with GnRH analogues as done in previous studies, has low
      efficacy. Recurrences are even more frequent after the use of two rIL-2 doses.

PMID- 20051693
TI  - No effect of parental age on risk of multiple sclerosis: a population-based
      study.
AB  - BACKGROUND: Genetic and environmental factors have important roles in multiple
      sclerosis (MS) susceptibility. A clear parent-of-origin effect has been shown in
      several populations. Advanced maternal age has been shown to be associated with
      adverse outcomes in offspring including chromosomal abnormalities. Advanced
      paternal age is associated with a number of adult onset disorders including
      schizophrenia and bipolar disorder. In a population-based Canadian cohort, we
      investigated whether there is any difference in parental age at birth for MS
      index cases compared to spouse controls. METHODS: Using the longitudinal Canadian
      database, we identified 5,681 MS index cases and 1,249 spouse controls with
      complete information on parental dates of birth, thereby allowing a calculation
      of the maternal and paternal ages at the birth of their children (MS index cases
      and spouse controls). RESULTS: No significant difference in maternal or paternal
      age at birth was found (average MS index case maternal age at birth = 27.3 years,
      average spouse control maternal age at birth = 27.0 years, p = 0.13; average MS
      index case paternal age at birth = 30.7 years, average spouse control paternal
      age at birth = 30.2 years, p = 0.37). CONCLUSIONS: Parental age at birth is not
      associated with susceptibility to MS.

PMID- 20051694
TI  - Predictors of vascular events after ischemic stroke: the China ischemic stroke
      registry study.
AB  - BACKGROUND/AIMS: To measure the risk of vascular event occurrence among
      postischemic stroke patients in mainland China. METHODS: In this multicenter
      prospective stroke registry study, we enrolled 1,951 patients diagnosed with
      acute ischemic stroke. Demographic data, prestroke risk factors, severity of
      neurological deficits and disability graded on the National Institutes of Health
      Stroke Scale (NIHSS), and modified Rankin Scale scores of each patient were
      measured and recorded. Patients were followed up regularly for 12 months after
      recruitment. Clinical endpoints were defined as occurrence of vascular events or
      death. RESULTS: We detected 103 cases with nonfatal vascular events and 27 cases
      that died of vascular events. Cumulative incidences of total vascular events,
      cerebrovascular events, and coronary artery diseases were 7.2, 5.0, and 1.8%,
      respectively, at 12 months after the initial ischemic stroke. Concomitant
      atherosclerotic-thrombotic diseases (HR, 1.68; 95% CI, 1.14-2.43) and baseline
      NIHSS (HR, 1.07; 95% CI, 1.03-1.11) were found to be the best predictors for
      further occurrence of a vascular event. Antiplatelet therapy (HR, 0.52; 95% CI,
      0.35-0.77) is associated with a lower risk of further vascular events.
      CONCLUSION: Our study provided valuable data on prognosis of acute ischemic
      stroke in Chinese patients.

PMID- 20051695
TI  - Maternal genitourinary infection appears to synergistically increase the risk of
      epilepsy in children of women with epilepsy.
AB  - BACKGROUND: Evidence indicates that maternal genitourinary infection during
      pregnancy is associated with increased risk of epilepsy in children and that
      children of women with epilepsy are substantially more likely to have epilepsy
      themselves. Research is lacking on whether maternal genitourinary infection has a
      different effect on children of women with epilepsy compared to children of women
      without epilepsy. METHODS: We conducted a retrospective cohort study using
      Medicaid data for 127,540 pregnancies, from 1996 to 2002, and children's data
      through 2008. Maternal epilepsy, genitourinary infections, and child epilepsy
      were identified. Epilepsy was diagnosed in 1.7% of the children in the cohort.
      RESULTS: There was a statistically significant interaction between maternal
      genitourinary infection and maternal epilepsy. Maternal genitourinary infection
      was strongly associated with increased risk of epilepsy in children of women with
      epilepsy (hazard ratio = 3.74, 95% CI = 1.67-8.40). Infection was more weakly
      associated with increased risk of epilepsy in children of women without epilepsy
      (hazard ratio = 1.23, 95% CI = 1.12-1.34). CONCLUSIONS: There is a significant
      association between genitourinary infection and childhood epilepsy, and the
      impact appears to be greater in children of women with epilepsy. This finding has
      implications for prenatal care of women with epilepsy as well as for research on
      antenatal risk factors for child epilepsy.

PMID- 20051696
TI  - Cerebral and systemic hemodynamic effects of intravenous bolus administration of
      propofol in neonates.
AB  - OBJECTIVES: To assess variability of systemic hemodynamics and its covariates
      following bolus propofol administration in (pre)term neonates, and to analyze the
      effect of propofol on cerebral tissue oxygenation index (TOI) and fractional
      tissue oxygen extraction measured by near-infrared spectroscopy. METHODS: In
      (pre)term neonates, we recorded mean arterial blood pressure (MABP), saturation
      (SaO(2)), heart rate (HR) and TOI from 5 min before up to 60 min after
      intravenous bolus propofol (3 mg kg(-1)) administration during elective chest
      tube removal. Covariate analysis included postmenstrual age (PMA <or= or >37
      weeks), postnatal age (PNA <or= or >10 days), comedication (fentanyl +/-
      midazolam) and congenital cardiopathy (yes/no). Fractional tissue oxygen
      extraction was calculated as (SaO(2) - TOI)/SaO(2). RESULTS: Twenty recordings in
      19 neonates were assessed. Following propofol administration, an abrupt, minor
      decrease in HR and SaO(2) was seen with fast recovery, while MABP decreased up to
      1 h. TOI decreased during the first 3 min, reflecting an imbalance between
      cerebral oxygen delivery and demand. Despite sustained decrease in MABP, TOI then
      returned to baseline, suggesting a better balance between oxygen delivery and
      demand. PNA <or=10 days, comedication and absence of cardiopathy were associated
      with more subtle decreases in cerebral oxygenation and faster recovery.
      CONCLUSIONS: Propofol-induced decrease in HR, SaO(2) and cerebral oxygenation is
      short lasting while a decrease in MABP is observed up to 60 min. The variability
      in the effects of propofol is influenced by PNA, comedication or cardiopathy.
      Near-infrared spectroscopy can be used to assess hemodynamic effects of hypnotics
      on the cerebral oxygenation.

PMID- 20051697
TI  - The interaction of the neuroprotective compounds riluzole and phenobarbital with
      AMPA-type glutamate receptors: a patch-clamp study.
AB  - BACKGROUND: Blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA)-type glutamate receptors is a promising pharmacological strategy in the
      treatment of neurodegenerative diseases. The aim of the study is to elucidate if
      there are direct interactions of riluzole and phenobarbital with AMPA-type
      receptor channels and to determinethe molecular pharmacological mechanisms.
      METHODS: The patch-clamp technique was used combining an ultrafast solution
      exchange system to investigate the interaction of riluzole and phenobarbital with
      recombinant AMPA-type glutamate receptor channels (homomeric GluR2flipGQ or
      nondesensitizing GluR2L504Y). RESULTS: A dose-dependent decrease in the relative
      peak current amplitude (rAmp) and the relative area-under-the-current curve
      (rAUC) were found after preincubation with 0.1 mmol/l or higher concentrations of
      riluzole. Furthermore, in coapplication experiments with GluR2L504Y, the
      application of 1 or 3 mmol/l riluzole showed a decrease in the current decay time
      constant, and a reopening current was observed at 3 mmol/l riluzole.
      Phenobarbital blocks AMPA receptor channels dose-dependently in the coapplication
      experiments, and reopening currents after removing glutamate and blocker were
      observed. A slight block effect after preincubation should indicate an additional
      competitive block effect. CONCLUSION: Riluzole and phenobarbital modulate AMPA
      type receptor channels separately, which could be both characterized as a
      combination of open-channel block and competitive-block mechanism.

PMID- 20051698
TI  - Spontaneous cranial osteomyelitis in an otherwise healthy ten-year-old male.
AB  - Frontal bone osteomyelitis is a relatively rare entity, particularly in the
      otherwise healthy pediatric population. Most cases trace their origins to either
      previous frontal sinusitis or trauma. In children, three origins for cranial
      osteomyelitis appear to dominate: Pott's puffy tumor, skull base osteomyelitis
      secondary to ear infection, or post-surgical complications. However, on extremely
      rare occasions, risk factors or etiology may not be ascertained. We present a
      case of spontaneous frontal bone osteomyelitis in a ten-year-old African-American
      male with no previous history of cranial surgeries, frontal sinusitis, or major
      trauma.

PMID- 20051699
TI  - Noncommunicating thoracolumbar intradural extramedullary arachnoid cyst in an 8
      year-old boy: intact removal by spontaneous delivery.
AB  - Noncommunicating spinal intradural extramedullary arachnoid cysts are an
      extremely rare cause of spinal cord compression. An 8-year-old boy presented with
      progressive paraparesis. Magnetic resonance imaging revealed a posterior
      intradural extramedullary arachnoid cyst extending from T(11) to L(3) vertebral
      bodies. The multilevel noncommunicating cyst was totally removed by simple
      delivery without rupture through a single-level laminoplasty. To our knowledge,
      no such case has been reported in the literature.

PMID- 20051700
TI  - Conventional and diffusion-weighted magnetic resonance imaging findings in a
      pediatric patient with a posterior fossa brain tumor and papilledema.
AB  - We present a case report of a 21-month-old female patient to highlight magnetic
      resonance (MR) imaging findings associated with papilledema in a pediatric
      patient with an intracranial tumor. The MR findings included optic disc
      elevation, dilated perioptic subarachnoid spaces, optic nerve tortuosity and
      restricted diffusion in the optic nerve heads, all of which resolved upon
      resolution of raised intracranial pressure (ICP) and papilledema. The case
      demonstrates that both conventional and diffusion-weighted MR imaging findings
      can detect the presence, and follow posttreatment resolution, of increased ICP
      and papilledema in a pediatric tumor patient. The postoperative resolution of
      optic disc elevation clearly indicates the intracranial tumor etiology.

PMID- 20051701
TI  - Acute tetraventricular hydrocephalus caused by mumps meningoencephalitis in a
      child.
AB  - Mumps is one of the common causes of childhood aseptic meningitis and
      encephalitis. Although central nervous system involvement is a common
      manifestation, hydrocephalus is a very rare complication of mumps, with just a
      few cases reported in the literature to date. Here we report on an 8-year-old boy
      with acute tetraventricular hydrocephalus caused by mumps meningoencephalitis and
      treated by external ventricular drainage and following ventriculoperitoneal
      shunt.

PMID- 20051702
TI  - Congenital cervical kyphosis in a child associated with tetraparesis: case
      report.
AB  - Congenital cervical kyphosis is a rare clinical condition. We describe an infant
      presenting with tetraparesis, rapidly progressing to phrenic paralysis and fatal
      respiratory insufficiency. Therapeutic options remain challenging. Surgical
      arthrodesis is technically difficult, and one report of a therapeutic
      thermoplastic body splint is described. Final outcome, however, is dismal. No
      long-term survivors have been described.

PMID- 20051703
TI  - Symptomatic Subdural Hygroma and Hydrocephalus following Chiari I Decompression.
AB  - BACKGROUND: The aim of the present case report is to describe an unusual
      complication of foramen magnum decompression (FMD) for the Chiari 1 hindbrain
      malformation and its successful management with non-operative measures. METHODS:
      A 2-year-old girl with the Chiari 1 malformation underwent FMD, including
      suboccipital craniotomy, C1 laminectomy and durotomy without opening the
      arachnoid. RESULTS: After initial postoperative improvement, the patient
      deteriorated, developing subdural hygromas and hydrocephalus. These were treated
      successfully with observation and acetazolamide. CONCLUSIONS: Subdural hygromas
      may complicate FMD. A slit valve opening in the arachnoid might be part of the
      pathophysiology. While surgical intervention may be necessary in some
      circumstances, non-operative measures may be effective as well.

PMID- 20051704
TI  - Chronic embitterment and organisational justice.

PMID- 20051705
TI  - Functional abdominal pain in childhood: from etiology to maladaptation.
AB  - OBJECTIVE: To review the extant literature on functional abdominal pain in
      childhood through the lens of the developmental psychopathology perspective and
      to systematize research results by means of a two-stage pathway model in which
      the emergence of functional abdominal pain and its potential transition into a
      somatoform adjustment disorder is outlined. METHODS: Using electronic searches
      for published studies and previous reviews about functional abdominal pain.
      RESULTS: An association of functional abdominal pain with internalizing symptoms,
      poor well-being of family members, major life events and daily stressors is
      found. The impact of stress on pain seems to be moderated by the children's
      coping style and their perceived competence and self-efficacy to manage the pain
      experience. There is evidence for the influence of modeling and operant
      mechanisms on pain experiences. A new term, 'somatoform adjustment disorder', and
      its relation to functional abdominal pain is discussed. CONCLUSIONS: It seems
      that those children with functional abdominal pain who cannot adapt to the pain
      indeed run the risk of developing a somatoform adjustment disorder.

PMID- 20051706
TI  - Exercise treatment for bipolar disorder: potential mechanisms of action mediated
      through increased neurogenesis and decreased allostatic load.
AB  - Outcomes are frequently suboptimal for patients with bipolar disorder who are
      treated with pharmacotherapy alone. Adjunct exercise has the potential to
      substantially improve acute and long-term outcomes, although how exercise would
      improve the course of bipolar disorder needs to be elucidated. We propose that
      exercise may improve mood and functioning by increasing neurogenesis and reducing
      allostatic load. We review data suggesting that exercise increases levels of
      brain-derived neurotrophic factor, which in turn increases neurogenesis and
      decreases allostatic load. Exercise as a psychosocial adjunct for bipolar
      disorder should be assessed with rigorous randomized clinical trials.

PMID- 20051707
TI  - A case study of salami slicing: pooled analyses of duloxetine for depression.
AB  - BACKGROUND: Publishing separate, yet very similar pieces of a single dataset
      across multiple papers is known as 'salami slicing'. This practice may be
      motivated by researchers wishing to increase their publication counts and by the
      desire to increase exposure of their findings. 'Salami slicing' may also be used
      by the drug industry to help widely disseminate positive findings regarding its
      products. Journal editors across many scientific disciplines have bemoaned such
      duplicative publications on several occasions. However, little research has been
      conducted on the frequency of such publication practices, and findings have been
      inconsistent. No research has investigated whether 'salami slicing' may also
      occur in publications presenting results from pooled analyses of clinical trials.
      METHODS: We examined the scientific literature on duloxetine as a treatment for
      depression, examining how data from clinical trials were reported across 43
      pooled analyses. RESULTS: The vast majority of pooled analyses (88%) had at least
      one author who was employed by the manufacturer of duloxetine. Several pooled
      analyses based on highly overlapping clinical trials presented efficacy and
      safety data that did not answer unique research questions, and thus appeared to
      qualify as salami publications. Six clinical trials had their data utilized as
      part of 20 or more separately published pooled analyses. CONCLUSIONS: Such
      redundant publications add little to scientific understanding and represent a
      poor use of peer reviewer and editorial resources.

PMID- 20051708
TI  - Functional MRI in the presurgical evaluation of patients with brain tumors:
      characterization of the statistical threshold.
AB  - We investigated whether an optimal statistical threshold could be obtained in
      healthy controls and patients with brain tumors undergoing presurgical functional
      MRI assessment. The volumes of activation of the primary motor cortex (PMC) and
      the lateral prefrontal cortex (PFC) were measured for the tumor and nontumor
      sides in 24 patients and 8 controls using four parameters; p values ranged
      between 10(-2) and 10(-31). The mean r value for first activation in the PMC was
      higher in controls than for both the tumor and nontumor sides in patients. The
      mean r value for 'first activation in the noise area' and 'PMC and PFC ratio' in
      controls was significantly different from the mean r value for the tumor and
      nontumor sides in patients (p < 0.05). The magnitude of the range of r values for
      the nontumor side was closer to the tumor side data than to the control data. It
      is imperative to evaluate functional MRI data with a wide range of statistical
      parameters, especially in the assessment of tumor patients.

PMID- 20051709
TI  - Microsurgical and stereotactic radiofrequency amygdalohippocampectomy for the
      treatment of mesial temporal lobe epilepsy: different volume reduction, similar
      clinical seizure control.
AB  - We compared stereotactic radiofrequency amygdalohippocampectomy (SAHE) with
      microsurgical amygdalohippocampectomy (AHE) in a group of 33 patients with mesial
      temporal lobe epilepsy in terms of hippocampal and amygdalar volume reductions
      and clinical outcome. In 23 subjects treated by SAHE, the hippocampal volume
      decreased by 58.0% (20.0; median, quartile range), with p = 10(-4), and the
      amygdalar volume decreased by 55.2% (23.8), with p = 10(-4). Two years after
      SAHE, 74% of patients were classified as class I, 22% as class II and 4% as class
      III. In 10 subjects treated by AHE, 83.5% (11.2) of the hippocampal and 53.1%
      (53.9) of the amygdalar volumes were removed (p = 0.05 and p = 0.005,
      respectively). Two years after the operation, 50% of the subjects were classified
      as class I, 30% as class II and 10% as class III and IV. To conclude, SAHE leads
      to a similar reduction of the amygdalar volume but to a significantly lower
      reduction of the hippocampal volume than AHE. The clinical outcome of SAHE is
      comparable with that of AHE.

PMID- 20051710
TI  - Pedunculopontine nucleus deep brain stimulation in a patient with primary
      progressive freezing gait disorder.
AB  - BACKGROUND: Pedunculopontine nucleus (PPN) deep brain stimulation (DBS) has
      recently been suggested for treatment of medication-unresponsive gait and axial
      symptoms in Parkinson's disease. Patients with the rare primary progressive
      freezing gait disorder (PPFG) have similar disabling symptoms and few therapeutic
      options. We report here on our experience with PPN DBS in treating a 76-year-old
      man with medication-refractory PPFG. METHODS: The patient was treated with staged
      PPN DBS and underwent careful pre- and postoperative clinical evaluations up to
      12 months after surgery. RESULTS: PPN DBS resulted in only mild improvement in
      symptoms after 12 months of stimulation. CONCLUSION: In this single case of a
      patient with PPFG, PPN DBS served only a limited role in treating his symptoms
      and adds to the very limited published literature describing patients treated
      with DBS at this brain target.

PMID- 20051711
TI  - Safety and function of a new clinical intracerebral microinjection instrument for
      stem cells and therapeutics examined in the Gottingen minipig.
AB  - BACKGROUND: A new intracerebral microinjection instrument (IMI) allowing multiple
      electrophysiologically guided microvolume injections from a single proximal
      injection path in rats has been adapted to clinical use by coupling the IMI to an
      FHC microTargeting Manual Drive, designed to be used with standard stereotactic
      frame-based systems and FHC frameless microTargeting Platforms. METHODS: The
      function and safety of the device was tested by conducting bilateral
      electrophysiologically guided microinjections of fluorescent microspheres in the
      substantia nigra of 4 Gottingen minipigs. RESULTS: The device was easy to handle
      and enabled accurate electrophysiologically guided targeting of the substantia
      nigra with minimal local tissue damage. CONCLUSION: The IMI is suitable for
      clinical use and may prove useful for various stereotactic procedures that
      require high levels of precision and/or three-dimensional distribution of
      therapeutics within the brain.

PMID- 20051712
TI  - Disposition of charged nanoparticles after their topical application to the skin.
AB  - The objective of this preliminary investigation was to examine the disposition of
      charged nanoparticles on and within the skin following their topical application
      and to explore whether the formulations have potential utility for the local
      delivery of an associated 'active' substance. Three nanoparticles (approx. 100 nm
      in diameter) were investigated: cationic amino-functionalized polystyrene, an
      anionic carboxyl-functionalized polystyrene and anionic poly-(L-lactide), into
      each of which the fluorophore N-(2,6-diisopropylphenyl)perylene-3,4-dicarboximine
      (PMI) was incorporated. Formulations were applied to excised porcine skin in
      vitro for 6 h. After cleaning the skin surface following treatment, the skin was
      either examined by laser scanning confocal microscopy or subjected to repeated
      tape-stripping and subsequent analysis of the removed stratum corneum (SC) for
      the presence of PMI. The cationic nanoparticles showed clear affinity for the
      negatively charged skin surface (in contrast to the anionic carriers) and
      delivered a significantly greater amount of the model 'active' agent (PMI) into
      the SC.

PMID- 20051713
TI  - Functional characterization of calcium-signaling pathways of human skin-derived
      mesenchymal stem cells.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) derived from adult human tissues are
      able to differentiate into various specialized cell types. In research, they can
      therefore be used like embryonic cells but without the ethical restrictions.
      Among the various human tissues, skin as a source is characterized by great
      accessibility and availability using noninvasive procedures and is without the
      risk of oncogenesis after transplantation. The recent isolation of MSCs has shown
      the lack of knowledge regarding their specific features, including the calcium
      signaling pathways. METHODS: In this study, we isolated MSCs from human skin
      biopsies (S-MSCs) and characterized them phenotypically and their calcium
      signaling pathways by the means of Ca2+ imaging and video microscopic
      experiments. RESULTS: The cytofluorimetric analysis of the expression of surface
      markers on S-MSCs revealed that they express the normal pattern present on MSCs.
      Interestingly, these cells appeared to be successfully cryopreserved at early
      passages. Calcium imaging on single S-MSCs shows that these cells did not display
      significant spontaneous activity or a response to a depolarizing agent. However,
      ATP or acetylcholine-induced intracellular calcium increase via ionotropic or
      metabotropic receptors, respectively. CONCLUSION: The results presented here
      reveal that S-MSCs show morphological and functional features that make them
      useful as an in vitro model to study cell differentiation.

PMID- 20051714
TI  - Responses to intradermal injections of substance P in psoriasis patients with
      pruritus.
AB  - BACKGROUND: Various mediators have been suggested for the pathogenesis of
      pruritus in psoriasis. METHODS: To investigate cutaneous responses of substance P
      in pruritic lesional and nonlesional areas of psoriasis patients and in healthy
      controls, substance P, saline and histamine were injected intradermally. After
      each injection, pruritus, flare and wheal were recorded. RESULTS: There was no
      statistical difference in the latency period, duration, area under the curve and
      maximum intensity of pruritus evoked by substance P (10(-5) and 10(-6) mol/l)
      between psoriasis and healthy control skin. Substance P (10(-5) mol/l) induced a
      tendency to a greater intensity of pruritus in lesional compared to nonlesional
      psoriatic skin (p = 0.08). Histamine produced a shorter itch latency period (p <
      0.05) and a lower maximum intensity of pruritus (p = 0.05) in lesional psoriasis
      skin than in healthy control skin. No significant difference in flare area was
      observed between the psoriasis patients and healthy controls. The histamine
      induced wheal was smaller in psoriasis patients than in healthy individuals (p <
      0.05). CONCLUSION: Intradermally injected substance P induced pruritus, flare and
      wheal in psoriasis patients. However, these responses did not differ
      significantly from those of the healthy controls.

PMID- 20051715
TI  - Identification of novel in vitro test systems for the determination of
      glucocorticoid receptor ligand-induced skin atrophy.
AB  - Topical glucocorticoids (GCs) demonstrate good anti-inflammatory effects but are
      limited by their side effect potential, with skin atrophy being the most
      prominent one. Thus, determining the atrophogenic potential of novel compounds is
      important. The aim of this study was to establish an in vitro skin atrophy model.
      A screening cascade was applied and GCs with a known atrophogenic potential were
      used as tool compounds. Five rodent and human cutaneous cell types/cell lines and
      2 human skin equivalents were tested. Known and suspected atrophy markers related
      to collagen metabolism and epidermal thickness were measured. Altogether, a
      combination of 7 different cellular assays with up to 16 markers each were
      investigated. A reproducible, more than 2-fold, regulation of the candidate
      markers by dexamethasone or clobetasol was found for: (a) matrix
      metalloproteinase (MMP) 1, 2, 3 and 9 expression in human keratinocytes, (b)
      COL1A1 and COL3A1 expression in 3T3 fibroblasts, and (c) epidermal thickness,
      collagen and MMP synthesis in the full-thickness skin model (FTSM). These 3
      models were further investigated with a panel of 4-5 GCs, demonstrating dose
      dependency and correlation with the atrophogenic potential of the tool compounds,
      qualifying them as potentially suitable. Finally, the predictability of these
      models for the in vivo situation was analyzed, testing a novel selective GC
      receptor agonist (SEGRA) in comparison to clobetasol. The results from the in
      vitro models suggested less atrophogenic effects for the SEGRA compound, which
      indeed was confirmed in the hr/hr rat skin atrophy model. In conclusion, a
      combination of 3 in vitro models based on 3T3 cells, human keratinocytes and FTSM
      with several readouts is recommended to determine atrophogenicity of GC receptor
      ligands. Further experiments are necessary to eventually reduce this panel and to
      demonstrate the true predictability for the clinic.

PMID- 20051716
TI  - Human rhinoviruses, allergy, and asthma: a clinical approach.
AB  - The prevalence of allergic diseases is increasing in Lithuania as in the world.
      The prevalence of allergic sensitization is often higher than 50% of the
      population. The "hygiene hypothesis" proposed that reduced immune-stimulation by
      infections may have resulted in the more widespread clinical expression of atopic
      disease. However, it alone does not provide an adequate explanation for the
      observed increase of allergic diseases. Human rhinovirus infections are the major
      infections with a worldwide distribution. Viral infections of the respiratory
      tract are the most common triggers of acute asthma exacerbations. These
      exacerbations are poorly responsive to current asthma therapies and new
      approaches to therapy are needed. The aim of this review is to present the
      current knowledge and clinical implications of human rhinovirus infection in
      allergy and asthma development and needs for further research. Recent evidence
      has shown that the immune responses to human rhinoviruses differ between
      asthmatic and nonasthmatic subjects. Novel insights into the mechanisms of virus
      induced asthma exacerbations support the possibility that viral infections may be
      involved in the epithelial cells damage, inflammation, and airway
      hyperresponsiveness as well as in profibrotic response and induction of airway
      remodeling. The data of original investigations support the concept that the
      immune stimulation by rhinovirus infections contributes to the development of
      asthma, when an atopic host is infected with human rhinoviruses. Early rhinoviral
      wheezing is the predictor of subsequent asthma development in high-risk children.
      Synergistic effect of allergic sensitization, allergen exposure, and viral
      infection was suggested in the increased risk of hospitalization for asthma in
      both children and adults. Timing of allergen exposure may be important in a
      synergistic outcome. The increased susceptibility to rhinovirus infections was
      identified in atopic asthma. This review also presents the current options on the
      treatment and prevention of virus-induced asthma. Further studies are needed in
      order to differentiate between the response to viruses of healthy and atopic or
      nonatopic asthmatic children and adults. New research data may lead to novel
      strategies in treatment and prevention of asthma exacerbations as well as
      prevention of asthma induction.

PMID- 20051717
TI  - [Late outcomes of on-pump and off-pump redo coronary artery bypass grafting].
AB  - Benefits of off-pump surgery are still widely debated in the literature comparing
      with conventional coronary artery bypass grafting. The aim of our study was to
      compare the late outcomes of patients who underwent on-pump redo coronary artery
      bypass surgery with those who had off-pump redo coronary artery bypass surgery.
      MATERIAL AND METHODS: Two groups of patients were compared. Group 1 consisted of
      34 patients who underwent off-pump redo coronary artery bypass surgery, and Group
      2 included 160 patients who underwent on-pump redo coronary artery bypass
      surgery. Both groups of patients were operated on by the same team of surgeons at
      the same time period. Groups did not differ by age, gender, functional class,
      preoperative myocardial infarction rate, and left ventricular function. More
      patients with hypertension were in the off-pump group. Significantly more grafts
      were performed in the on-pump group. Survival, presence of angina, reoccurrence
      of postoperative myocardial infarction, necessity of percutaneous transluminal
      coronary angioplasty and reoperations were evaluated in late follow-up period.
      The duration of follow-up was 3.37+/-2.15 years in the off-pump group and 3.27+/
      2.36 years in the on-pump group. RESULTS: Survival after 6 years in the off-pump
      and on-pump redo coronary artery bypass surgery groups was 85.3% and 83.6%,
      respectively (P=0.758). Five years after redo operation, 54.9% of patients who
      underwent off-pump coronary artery bypass surgery and 69.3% of patients who
      underwent on-pump coronary artery bypass surgery had no angina (P=0.174). There
      were no major cardiac events (percutaneous transluminal coronary angioplasty,
      death, myocardial infarction, and reoperations) after 6 years in 69.7% of
      patients in the off-pump group and 76.9% of patients in the on-pump group
      (P=0.343). Five years after redo surgery, 79.4% of patients in the off-pump group
      and 91.9% in the on-pump group were free of percutaneous transluminal coronary
      angioplasty (P<0.02). CONCLUSIONS: There was no difference in survival despite
      the fact that patients in the on-pump group received more grafts than those in
      the off-pump group. Recurrence of angina and incidence of major cardiac events
      were almost equal in both the groups. Percutaneous transluminal coronary
      angioplasty was more frequently performed in the patients of off-pump group at
      late follow-up.

PMID- 20051718
TI  - Characteristics and management of acute heart failure patients in a single
      university hospital center.
AB  - OBJECTIVE: To evaluate the causes of acute heart failure, complications,
      management, and outcomes. MATERIAL AND METHODS: A total of 200 patients with
      diagnosed de novo acute heart failure (27.5%) or worsening chronic heart failure
      (72.5%) were treated at the Department of Cardiology, Hospital of Kaunas
      University of Medicine, which was participating in the Euro Heart Failure Survey
      II (EHFS-II). The patients were divided into five groups: 1) chronic
      decompensated heart failure (66.0%); 2) pulmonary edema (13.0%); 3) hypertensive
      heart failure (7.5%); 4) cardiogenic shock (11.0%); and 5) right heart failure
      (2.5%). RESULTS: Hypertensive and coronary heart diseases were the most common
      underlying conditions of acute heart failure. Noncompliance with the prescribed
      medications was present as the most frequent precipitating factor in more than
      half of the cases. Left ventricular ejection fraction of >45% was found in 28.64%
      of cases. Intravenous diuretics (74.5%), nitrates (44.0%), and heparin (71.0%)
      were the most widely used in the acute phase. At discharge from hospital, 96.69%
      of patients were given diuretics; 80.11%, angiotensin-converting enzyme
      inhibitors; and 62.43%, beta-blockers. The mean duration of inhospital stay was
      13 days; death rate was 9.5%: after 3 months and 12 months, it was 7.5% and
      11.5%, respectively. CONCLUSION: Preserved systolic function, multiple
      concomitant diseases, and high mortality rates were observed in a substantial
      proportion of the patients hospitalized due to acute heart failure. The
      management of the patients in a university hospital center was performed in
      accordance with the international guidelines.

PMID- 20051719
TI  - Three-part Oppel-Kundt illusory figure.
AB  - The Oppel-Kundt illusion was examined in the psychophysical experiments with the
      classical two-part stimuli and modified three-part figures. The modified versions
      comprised either one filled medial interval and two empty flanking intervals or
      one empty space situated in between two fillings. The illusion was measured as a
      function of the number of filling elements in the referential parts of the
      figures. The curves obtained by two modified figures and by the original two-part
      stimulus were quite similar in shape, but the magnitudes of the illusions
      differed significantly. The figure with two filled intervals yielded about twice
      stronger illusory effect than the contrasting figure with a single filled and two
      empty intervals. The two-part stimulus showed the illusion magnitudes in the
      midst. Our assumption suggests the illusory effect being related particularly to
      over estimations of the filled interval when compared with the empty interval
      displayed side-to-side. The unfilled interval might not contribute to the
      illusion.

PMID- 20051720
TI  - Laser Doppler vibrometry of the middle ear in humans: derivation dependence,
      variability, and bilateral differences.
AB  - OBJECTIVE: Derivation dependence, inter- and intrasubject/intertest variability,
      bilateral differences of the eardrum vibration characteristics have been
      investigated using laser Doppler vibrometry (LDV). MATERIAL AND METHODS: A total
      of 31 normally hearing adults were examined. In each subject, both ears were
      consecutively stimulated by the chirp acoustic stimulus that covered 500-3700-Hz
      frequencies. The laser beam was directed to and the reflection was consecutively
      picked up from the tympanic membrane surface. RESULTS: LDV curves derived from
      different eardrum loci possessed dissimilar characteristics. The derivation area
      dependence was particularly apparent for the stimulus frequency constituents
      above 1500 Hz. The intersubject variability of LDV parameters exceeded the
      intrasubject/intertest one. The intersubject divergences looked selectively
      distinct for the frequencies over 2000 Hz. Under repeated recordings, LDV
      parameters remained stable. The intertest differences, if appeared, concerned
      predominantly the magnitudes of separate frequency bands. LDV waveforms
      registered by experienced and beginner investigators were alike. Bilaterally
      derived LDV curves regularly differed from each other. In individual cases, the
      bilateral divergences approximated the intersubject deviation. CONCLUSIONS: The
      derivation area on the eardrum should be taken into account when estimating the
      actual LDV recording. Over repeated recordings in separate individuals, LDV
      waveforms are stable while the experience of investigator has slight if any
      influence on the principal LDV characteristics. Due to bilateral differences in
      the middle ear transfer function, in LDV testing of the ear suspected to the
      pathology, LDV recording from the opposite healthy ear could hardly be taken as
      an appropriate reference sample.

PMID- 20051721
TI  - [Analysis of dental caries prevention program in 7-12-year-old Lithuanian
      schoolchildren].
AB  - OBJECTIVE: The present study aimed to assess dental status in 7-12-year-old
      Lithuanian children and to evaluate the extent and the efficiency of the Pit and
      Fissure Sealing in Permanent Molars program. MATERIAL AND METHODS: This cross
      sectional study was performed between September 2007 and May 2008. Children, aged
      7-12 years, from secondary schools in five biggest cities of Lithuania were
      invited for the examination using a cluster random sampling method. The data for
      the present study were collected following the general principles for basic oral
      health surveys of the World Health Organization. RESULTS: The prevalence of
      dental caries was 85.5%, 88.9%, and 70.6% in 7-8-, 9-10-, and 12-year olds,
      respectively. The prevalence of dental caries in permanent molars increased with
      age and became as high as 57.7% in 12-year-old children. The data showed that the
      mean number of sealed teeth depends on the county and ranged from 0.83 (1.31) to
      1.45 (1.85) in 7-8-year olds, from 0.95 (1.29) to 2.54 (1.15) in 9-10-year olds,
      and from 0.26 to 2.13 (1.15) in 12-year olds. CONCLUSIONS: The prevalence and
      incidence of dental caries in 7-12-year-old Lithuanian children are high. Only
      half of all examined children have at least one sealed molar. The financial
      resources allocated for the Pit and Fissure Sealing in Permanent Molars program
      were used insufficiently; therefore, there is a need for systematic measures in
      order to improve the efficacy of the aforementioned program.

PMID- 20051722
TI  - [Physical and mental health of stroke survivors and their daily activities].
AB  - The aim of the study was to compare the quality of life between stroke survivors
      and controls with respect to their health, daily activities, and emotional
      status. CONTINGENT AND METHODS OF THE STUDY: The studied group consisted of 508
      25-84-year-old inhabitants of Kaunas city who have survived first-onset stroke.
      The control group consisted of 508 age- and sex-matched randomly selected
      inhabitants of Kaunas city who had not experienced stroke. The SF-12 Quality of
      Life Questionnaire was used for the study. Logistic regression was used to
      compare quality of life with respect to health, daily activities, and emotional
      status. RESULTS: Only 1.0% of stroke survivors evaluated their health as
      excellent or very good, compared to 24.4% of the controls (P=0.0005); the
      respective percentages of those who evaluated their health as poor or fair were
      78.9% and 26.4% (P=0.0005). Health significantly limited moderate activities in
      35.2% of stroke survivors and 3.5% of controls (P=0.0005). During the last 4
      weeks, health status or emotional problems most of the time or a little of the
      time impeded social activities in 19.3% of stroke survivors and 1.6% of controls
      (P<0.05). When comparing with respect to age, sex, and diseases (arterial
      hypertension, myocardial infarction, atrial fibrillation, diabetes mellitus,
      transient ischemic attack), stroke had the greatest negative effect on social
      activities (odds ratio, 36.7), caused sadness (odds ratio, 16.0), and
      significantly limited home activities (odds ratio, 15.5). CONCLUSIONS: Less that
      one-third (28.2%) of stroke survivors evaluated their health as poor, and 50.7%
      as fair as compared to 1.8% and 24.6% of controls, respectively. Stroke
      significantly impaired the subjects' emotional status and limited their daily
      activities.

PMID- 20051723
TI  - Maternal socioeconomic and lifestyle factors during pregnancy and the risk of
      congenital heart defects.
AB  - The objective of study was to estimate the importance of maternal socioeconomic
      and lifestyle factors during pregnancy in the risk of congenital heart defects in
      Kaunas infant population in 1999-2005. MATERIAL AND METHODS: An epidemiological
      case-control study was conducted. The study comprised 187 newborns with
      congenital heart defects (cases) and 643 randomly selected newborns without any
      defects (controls), born in Kaunas city during 1999-2005. Modern epidemiological
      methods were used for data analysis. A multivariate logistic regression was used
      to determine adjusted risk factors of congenital heart defects. RESULTS: The
      logistic multivariate regression analysis showed that low and moderate maternal
      education significantly increased the risk of congenital heart defects (primary
      or basic [OR=3.43; 95% CI, 1.54-7.64] and secondary [OR=1.56; 95% CI, 1.00-2.45]
      vs advanced vocational or higher education). The housewives and workers had a
      higher risk of delivering a newborn with congenital heart defects than the office
      workers (OR=2.34; 95% CI, 1.34-4.10 and OR=1.28; 95% CI, 0.79-2.07,
      respectively). Maternal smoking during pregnancy tended to increase the risk of
      congenital heart defects by 48% (OR=1.48; 95% CI, 0.82-2.67). CONCLUSIONS:
      According to our study results, unfavorable maternal socioeconomic factors and
      smoking during pregnancy increased the risk of congenital heart defects.

PMID- 20051724
TI  - Psychosocial job characteristics, social support, and sense of coherence as
      determinants of mental health among nurses.
AB  - OBJECTIVE: Employment in human service occupations as nursing is reported to
      display high risk for mental health, and occupational stress has been found to be
      one of the major work-related health problems. The objective of the study was to
      explore the associations between psychosocial job characteristics, social
      support, and internal resources as determinants of mental health status in a
      sample of Kaunas district nurses. MATERIAL AND METHODS: A survey was conducted
      among the nurses of Kaunas district community in 2008-2009. A total of 638 nurses
      were randomly selected, and 372 filled in the questionnaire (response rate,
      58.3%). Mental distress was measured using the Goldberg 12-item General Health
      Questionnaire and psychosocial job characteristics using the Swedish version of
      the Karasek Demand-Control questionnaire. Sense of coherence was measured by the
      three-item version questionnaire. The logistic regression was performed. RESULTS:
      Less than one-third (23.0%) of nurses had symptoms of mental distress; 31.9% of
      nurses had weak sense of coherence. High job demands were associated with mental
      distress after adjustment for age, smoking, alcohol consumption, physical
      activity, job control, social support, sense of coherence, family crisis, self
      rated health as compared to one year ago (OR=2.15; 95% CI, 1.07-4.30), low job
      control (OR=1.22; 95% CI, 0.64-2.31), job strain-low social support at work
      (OR=3.78; 95% CI, 2.08-6.87). CONCLUSIONS: Mental distress among the nurses of
      Kaunas district was associated with adverse psychosocial job characteristics. Job
      strain-low social support at work was the strongest risk factor for mental
      distress among nurses. Strong sense of coherence as personal characteristic
      served as a buffer, protecting nurses against the development of mental health
      problems.

PMID- 20051725
TI  - Biomedical physics in continuing medical education: an analysis of learning
      needs.
AB  - OBJECTIVE: To examine the learning and practice needs of medical professionals in
      the field of continuing education of biomedical physics in Lithuania. MATERIAL
      AND METHODS: The study was based on a questionnaire survey of 309 medical
      professionals throughout Lithuania, 3 focus group discussions, and 18 interviews
      with medical and physics experts. RESULTS: The study showed that medical
      professionals lack knowledge of physics: only 15.1% of the respondents admitted
      that they had enough knowledge in biomedical physics to understand the
      functioning of the medical devices that they used, and 7.5% of respondents
      indicated that they had enough knowledge to understand and adopt medical devices
      of the new generation. Physics knowledge was valued more highly by medical
      professionals with scientific degrees. As regards continuing medical education,
      it was revealed that personal motivation (88.7%) and responsibility for patients
      (44.3%) were the most important motives for upgrading competencies, whereas
      workload (65.4%) and financial limits (45.3%) were the main obstacles. The most
      popular teaching methods were those based on practical work (78.9%), and the
      least popular was project work (27.8%). CONCLUSIONS: The study revealed that
      biomedical physics knowledge was needed in both specializations and practical
      work, and the most important factor for determining its need was professional
      aspirations. Medical professionals' understanding of medical devices, especially
      those of the new generation, is essentially functional in nature. Professional
      upgrading courses contain only fragmented biomedical physics content, and new
      courses should be developed jointly by experts in physics and medicine to meet
      the specialized needs of medical professionals.

PMID- 20051726
TI  - [Acquired Immunodeficiency Syndrome and opportunistic infections].
AB  - This article presents a clinical case of late diagnosis of cerebral toxoplasmosis
      and cytomegalovirus retinitis of right eye in a 32-year-old patient who was
      unaware of her HIV status. In addition, this article reviews the literature
      reflecting clinical, diagnostic, and treatment issues of some opportunistic
      infections in AIDS.

PMID- 20051727
TI  - Incidence of injury among adolescent soccer players: a comparative study of
      artificial and natural grass turfs.
AB  - OBJECTIVE: To investigate the incidence of acute injuries and soccer-related
      chronic pain from long-term training and during matches in adolescent players
      using natural grass turfs (NT) and artificial turfs (AT). DESIGN: Case-controlled
      prospective study. SETTING: Institutional-level Federation Internationale de
      Football Association Medical Centre of Excellence. PARTICIPANTS: Youth soccer
      players (12-17 years of age) from 6 teams, with a predominant tendency to train
      on either NT or AT, were included. Of 332 players enrolled in this study, 301
      remained to completion. INTERVENTIONS: Medically diagnosed acute injuries and
      chronic pain were recorded daily by team health care staff throughout 2005, and
      reports were provided monthly to the authors. ASSESSMENT OF RISK FACTORS:
      Noninvasive prospective study. INDEPENDENT VARIABLES: Age and turf type. MAIN
      OUTCOME MEASURES: Acute injuries per 1000 player hours on each surface and
      chronic complaints per 1000 player hours were evaluated according to frequency of
      surface used > or = 80% of the time. Incidence rate ratio (IRR) of acute injuries
      and chronic complaints during play on NT and AT was calculated. RESULTS: There
      was no significant difference in the incidence of acute injuries between the 2
      surfaces during training and competition. However, the AT group showed a
      significantly higher incidence of low back pain during training (IRR, 1.62; 95%
      confidence interval, 1.06-2.48). Early adolescence and prolonged training hours
      were factors associated with an increased incidence of chronic pain in the AT
      group. CONCLUSION: Adolescent players routinely training on AT for prolonged
      periods should be carefully monitored, even on AT conforming to new standards.

PMID- 20051728
TI  - Comparison of active stretching technique and static stretching technique on
      hamstring flexibility.
AB  - OBJECTIVES: To compare a passive and an active stretching technique to determine
      which one would produce and maintain the greatest gain in hamstring flexibility.
      To determine whether a passive or an active stretching technique results in a
      greater increase in hamstring flexibility and to compare whether the gains are
      maintained. DESIGN: Randomized controlled trial. SETTING: Institutional.
      PARTICIPANTS: Sixty-five volunteer healthy subjects completed the enrollment
      questionnaire, 33 completed the required 75% of the treatment after 6 weeks, and
      22 were assessed 4 weeks after the training interruption. INTERVENTION: A 6-week
      stretching program with subjects divided into 2 groups with group 1 performing
      active stretching exercises and group 2 performing passive stretching exercises.
      MAIN OUTCOME MEASURES: Range of motion (ROM) was measured after 3 and 6 weeks of
      training and again 4 weeks after the cessation of training and compared with the
      initial measurement. RESULTS: After 3 weeks of training, the mean gain in group 1
      (active stretching) on performing the active knee extension range of motion
      (AKER) test was 5.7 degrees, whereas the mean gain in group 2 (passive
      stretching) was 3 degrees (P = .015). After 6 weeks of training, the mean gain in
      group 1 was 8.7 degrees , whereas the mean gain in group 2 was 5.3 degrees (P =
      .006). Twenty-two subjects were reassessed 4 weeks after the cessation of the
      training with the maintained gain of ROM in group 1 being 6.3 degrees , whereas
      the maintained gain in group 2 was 0.1 degrees (P = .003). CONCLUSIONS: Active
      stretching produced the greater gain in the AKER test, and the gain was almost
      completely maintained 4 weeks after the end of the training, which was not seen
      with the passive stretching group. Active stretching was more time efficient
      compared with the static stretching and needed a lower compliance to produce
      effects on flexibility.

PMID- 20051729
TI  - No relation between pelvic belt tests and abdominal muscle thickness behavior in
      athletes with long-standing groin pain. Measurements with ultrasound.
AB  - OBJECTIVE: To investigate whether abdominal muscle thickness in athletes with
      long-standing adduction-related groin pain (LAGP) differs between subgroups with
      a positive or no response to a pelvic belt. The response to a pelvic belt is
      defined positive in case of a decrease > or = 1 on a Likert pain scale (0-10)
      during the squeeze test (SQT) or a decrease > or = 1 on the active straight leg
      raise (ASLR) test score (0-10). DESIGN: Cross-sectional study. SETTING: Physical
      therapy practice. PATIENTS: Fifty athletes with LAGP. INDEPENDENT VARIABLES:
      Squeeze test and ASLR test. MAIN OUTCOME MEASURES: First, the effect of a pelvic
      belt on pain during the SQT and the ASLR test score was evaluated. Then,
      thickness of m. transversus abdominis (TA) and m. obliquus internus (OI) was
      measured using ultrasound during rest, ASLR left and right, and SQT. RESULTS: Of
      the 50 participants, 25 (50%) experienced a decrease in pain during the SQT when
      wearing a pelvic belt and 10 (20%) improved in ASLR performance with a pelvic
      belt. Thickness of TA and OI at rest (both cases P > .08) and relative thickness
      compared with rest during tasks (in all cases P > .12) revealed no significant
      difference when comparing the 2 subgroups based on the belt response during the
      SQT or ASLR. CONCLUSIONS: Using these methods, abdominal muscle thickness
      behavior in athletes with LAGP did not differ between the subgroups based on a
      positive or no response to a pelvic belt. However, the ultrasound method used may
      not have been sensitive enough to reveal differences between groups.

PMID- 20051730
TI  - A preliminary study of subsymptom threshold exercise training for refractory post
      concussion syndrome.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of subsymptom threshold
      exercise training for the treatment of post-concussion syndrome (PCS). DESIGN:
      Prospective case series. SETTING: University Sports Medicine Concussion Clinic.
      PARTICIPANTS: Twelve refractory patients with PCS (6 athletes and 6 nonathletes).
      INTERVENTION: Treadmill test to symptom exacerbation threshold (ST) before and
      after 2 to 3 weeks of baseline. Subjects then exercised 5 to 6 days per week at
      80% ST heart rate (HR) until voluntary peak exertion without symptom
      exacerbation. Treadmill testing was repeated every 3 weeks. MAIN OUTCOME
      MEASURES: Adverse reactions to exercise, PCS symptoms, HR, systolic blood
      pressure (SBP), achievement of maximal exertion, and return to work/sport.
      RESULTS: Pretreatment, ST occurred at low exercise HR (147 + or - 27 bpm) and SBP
      (142 + or - 6 mm Hg). After treatment, subjects exercised longer (9.75 + or -
      6.38 minutes to 18.67 + or - 2.53 minutes, P = .001) and achieved peak HR (179 +
      or - 17 bpm) and SBP (156 + or - 13 mm Hg), both P < .001 versus pretreatment,
      without symptom exacerbation. Time series analysis showed significant change in
      rate of symptom reduction for all subjects and reduced mean symptom number in
      8/11. Rate of PCS symptom improvement was related to peak exercise HR (r = -0.55,
      P = .04). Athletes recovered faster than nonathletes (25 + or - 8.7 vs 74.8 + or 
      27.2 days, P = .01). No adverse events were reported. Athletes returned to sport
      and nonathletes to work. CONCLUSIONS: Treatment with controlled exercise is a
      safe program that appears to improve PCS symptoms when compared with a no
      treatment baseline. A randomized controlled study is warranted.

PMID- 20051731
TI  - The effect of a one-leg cycling aerobic training program during the
      rehabilitation period in soccer players with anterior cruciate ligament
      reconstruction.
AB  - OBJECTIVES: To examine cardiorespiratory fitness, resting cardiac parameters, and
      muscle oxygenation changes in soccer players having undergone anterior cruciate
      ligament reconstruction and to assess the benefits of a one-leg cycling (OLC)
      aerobic training program performed during the rehabilitation period. DESIGN:
      Randomized clinical trial. SETTING: Outpatient clinic, primary care. PATIENTS:
      Twenty-four, male, regional-level soccer players who had undergone surgical
      reconstruction of the anterior cruciate ligament of the knee. INTERVENTION:
      Patients were randomly assigned to 1 of 2 groups: either an individualized OLC
      aerobic training program with the untreated leg plus a rehabilitation program
      (training group, TG) or a group that received the same rehabilitation program but
      without aerobic training (control group, CG). MAIN OUTCOME MEASURES: Outcome
      measurements assessed before (T1) and after 6 weeks (T2) were stroke volume (SV)
      and end-diastolic volume (EDV) during resting cardiac echography measurement and
      peak work rate (W(peak)), peak O(2) uptake (VO(2)peak), peak minute ventilation
      (VE(peak)), first and second ventilatory threshold (VT1 and VT2), leg muscle
      oxygenation (LMO(2)), and blood volume (LMBV) during maximal graded tests
      performed with the untreated leg. RESULTS: At T1, there was no significant
      difference between TG and CG. For TG, W(peak), VE(peak), VT1, VT2, LMO(2), and
      LMBV at each work rate were significantly higher at T2 than at T1. For CG,
      W(peak), VO(2)peak, VE(peak), VT2, SV, and EDV decreased significantly at T2 in
      comparison with T1. CONCLUSIONS: One-leg cycling training could involve specific
      adaptations in comparison to a standard rehabilitation program. Moreover, OLC
      training during rehabilitation seems to stop the effects of hypoactivity.

PMID- 20051732
TI  - Core stability: inter- and intraobserver reliability of 6 clinical tests.
AB  - OBJECTIVE: Core stability is a complex concept within sports medicine and is
      thought to play a role in sports injuries. There is a lack of reliable and valid
      clinical tests for core stability. The inter- and intraobserver reliability of 6
      tests commonly used to assess core stability was determined. DESIGN: A video of
      the tests was shown to 6 observers. A second observation took place 5 weeks later
      with the same observers. SETTING: Sports medicine department of a hospital.
      PARTICIPANTS: Forty male athletes. ASSESSMENT OF VARIABLES: Core stability was
      rated as poor, moderate, good, or excellent by each observer for each of the 6
      tests. MAIN OUTCOME MEASURES: Inter- and intraobserver reliability. RESULTS: The
      mean score of all tests was 13.4% poor, 33.3% moderate, 40.1% good, and 13.2%
      excellent. The intraclass correlation coefficients (ICCs 2,1) for the
      interobserver reliability for frontal, sagittal, and transverse plane evaluation
      were 0.09, 0.32, and 0.51, respectively. The ICCs for the unilateral squat, the
      lateral step-down, and the bridge were 0.41, 0.39, and 0.36, respectively. The
      ICCs for the intraobserver reliability for frontal, sagittal, and transverse
      plane evaluation were 0.31, 0.40, and 0.55, respectively. The ICCs for the
      unilateral squat, the lateral step-down, and the bridge were 0.55, 0.49, and
      0.21, respectively. CONCLUSIONS: The 6 clinical core stability tests are not
      reliable when a 4-point visual scoring assessment is used. Future research on
      movement evaluation should be focused on more specific rating methods and
      training for the observers.

PMID- 20051733
TI  - Upper respiratory tract infection symptoms in ultramarathon runners not related
      to immunoglobulin status.
AB  - OBJECTIVE: To determine the association between variation in exercise load,
      immunoglobulin (Ig) status, and self-reported symptoms of upper respiratory tract
      infection (URTI) in ultramarathon runners. DESIGN: Longitudinal observational
      field study. SETTING: Four weeks before and 2 weeks after an 86.5-km Comrades
      Marathon, South Africa. PARTICIPANTS: Fourteen randomly selected, amateur, male,
      ultramarathon runners. MAIN OUTCOME MEASURES: Daily record of training and URTI
      symptom incidence. Salivary IgA and IgM at 28 days, 14 days, and 1 day (01PRE)
      before the race, immediately post race (IPR) and 1 (01 PR), 3, and 14 days post
      race. Serum cortisol, IgG, IgM, and IgA concentrations at 01PRE, IPR, and 01PR.
      RESULTS: Mean weekly training distance varied from 89.4 kilometers per week (28.9
      kilometers per week) to 4.2 kilometers per week (6.7 kilometers per week).
      Absolute and relative mucosal IgA and IgM concentrations were unaffected by pre
      race taper in training volume (P > 0.05). IgA and IgM secretion rates decreased
      post race (P = 0.018; 0.008), returning to baseline by 01PR. Blood leukocyte,
      serum cortisol, and serum IgG concentrations increased at IPR (P < 0.001, <0001)
      and 01PR (P = 0.009), respectively. Upper respiratory tract infection symptom
      incidence was highest at 28PRE and 7 to 14 days post race but not related to
      salivary IgA and IgM secretion rates. Eight subjects (57%) who reported URTI
      symptoms pre race also reported these during days 7 to 14 post race. CONCLUSIONS:
      Upper respiratory tract infection symptom incidence was not associated with
      secretory Ig concentrations. Reactivation of pre-race viruses during the 2 weeks
      post race and exercise-induced inflammatory response are proposed as causes of
      the elevated URTI incidence at 28PRE and 7 to 14 days post race.

PMID- 20051735
TI  - Agreement between an ingestible telemetric sensor system and a mercury
      thermometer before and after linear regression correction.
AB  - OBJECTIVES: To evaluate the use of the CorTemp ingestible sensor system to
      monitor athletes in the prevention of thermal injuries, 3 objectives were
      established: (1) to determine the agreement between the system and a mercury
      thermometer and quantify the effect of exceeding the recommended yearly
      manufacturer calibration, (2) to establish the effect of individual sensor
      correction on agreement, and (3) to determine the quantity of data required for
      effective correction. DESIGN: Validation study. PARTICIPANTS: Ninety-four
      ingestible sensors. INTERVENTIONS: (1) Five comparisons were made between each
      sensor and a mercury thermometer across the range of 33 to 41 degrees C. This was
      performed immediately, and 14 to 18 months, after factory calibration. (2) Linear
      regression equations were created and used to correct sensor readings at
      approximately 37 degrees C; the corrected value was compared with the mercury
      thermometer. (3) Linear regression equations were created for each sensor using 2
      to 5 data points. MAIN OUTCOME MEASURES: Systematic bias and random error (95%).
      RESULTS: (1) Systematic bias + or - random error (95%) was 0.73% + or - 0.23% (
      approximately 0.27 + or - 0.09 degrees C) and 0.54% + or - 0.28% ( approximately
      0.22 + or - 0.11 degrees C) immediately and 14 to 18 months post factory
      calibration, respectively. (2) Regression correction improved agreement through
      reductions in systematic bias. (3) Individualized equations using a minimum of 3
      comparisons were required to reduce agreement to + or - 0.10 degrees C; the use
      of 5 comparisons minimized the number of readings exceeding + or - 0.10 degrees
      C. CONCLUSIONS: (1) The CorTemp system inflates temperature measurements compared
      with a mercury thermometer. (2) Individual sensor calibration is warranted. (3)
      Correction equations should use a minimum of 3, preferably 5, comparisons. After
      regression correction, the system displays satisfactory accuracy for preventative
      monitoring.

PMID- 20051734
TI  - Bike Transalp 2008: liquid intake and its effect on the body's fluid homeostasis
      in the course of a multistage, cross-country, MTB marathon race in the central
      Alps.
AB  - OBJECTIVES: To investigate the drinking behavior of the participants in a multi
      day mountain bike (MTB) cross-country competition, to monitor its effect on the
      body's fluid compartments and body mass, and to evaluate the prevalence of
      exercise-associated dysnatremia. DESIGN: Descriptive field study. SETTING: The
      Jeantex Bike Transalp Competition 2008 (8 stages; 665.40 km; 21 691 m height).
      PARTICIPANTS: Twenty-five male, amateur MTB cyclists. INDEPENDENT VARIABLES:
      Reported fluid intake during the race, air temperature. MAIN OUTCOME MEASURES:
      Changes in body mass and body composition from pre to post race and throughout
      the competition week, serum sodium concentration at finish line of stages 5 and
      6. RESULTS: Mean (+ or - SD) hourly fluid intake during the race correlated with
      air temperature (r = 0.868, P < .05) and ranged between 494 + or - 191 mL/h and
      754 + or - 254 mL/h. In absence of exercise-induced hyponatremia (EAH) cases, we
      report 5 and 4 cases of asymptomatic post-race hypernatremia, on days 5 and 6,
      respectively. When related to race time and body mass, the liquid intake during
      the race (in mL x kg(-1) x h(-1)) correlated with post-race serum sodium
      concentration (stage 5: r = -0.463, P < .05, n = 24; stage 6: r = -0.589, P <
      .01, n = 23); no correlation was found between the change in body mass from pre
      to post race and serum sodium concentration at finish line. CONCLUSIONS: Ad
      libitum fluid consumption during competition was spontaneously adjusted to the
      unsettled weather conditions in the course of the 2008 "Bike Transalp." The
      inverse linear relationship between hourly fluid intake and post-race serum
      sodium concentrations suggests underdrinking to be one contributing factor to the
      high reported incidence of hypernatremia in the absence of EAH. Experimental
      studies are requested to confirm this hypothesis and to further examine the
      pathogenesis of exercise-associated dysnatremia. In this setting, body mass
      monitoring was not an accurate instrument to control body fluid homeostasis.

PMID- 20051736
TI  - Alternations of heart rate variability at lower altitude in the predication of
      trekkers with acute mountain sickness at high altitude.
AB  - OBJECTIVE: To determine the change and relationship of spectral components of
      heart rate variability (HRV) measurements in subjects with or without acute
      mountain sickness (AMS) at both low and high altitude. DESIGN: A prospective
      study. SETTING: A 12-day itinerary by trekking to the Namche Bazaar, 3440 m in
      Nepal. PARTICIPANTS: A total of 32 subjects were recruited. INTERVENTIONS: The
      alternations were measured by heart rate (HR), arterial oxygen saturation
      (SpO(2)), and spectral analysis of HRV at sea level, 1317 m, 3440 m, 1317 m, and
      sea level, respectively. MAIN OUTCOME MEASURES: Spectral analysis of HRV.
      RESULTS: There were statistically significant increases in HR and decreases in
      SpO(2) in all subjects at high altitude. In HRV, the values of R-R interval,
      total variance, high frequency (HF), low frequency (LF), and HF% were
      significantly lower at 3440 m than at sea level, respectively (P < 0.05). The
      subjects with AMS had significantly lower total variance, HF, and HF%,
      respectively, but higher LF:HF ratio (P < 0.05) at 3440 m. Subjects with both HF%
      < 20% (nu) and LF:HF ratio > 1.3 measured at 1317 m had odds ratios of 7.00 (95%
      confidence interval, 1.11 to 44.06; P = 0.047) to get AMS at 3440 m. CONCLUSIONS:
      The HRV measurements in total variances, HF, and HF% in trekkers with AMS were
      statistically significantly lower at high altitude. HF% < 20% (nu) or LF:HF ratio
      > 1.3 at lower altitudes could be an important predication parameter of trekkers
      with AMS at higher altitudes.

PMID- 20051737
TI  - Bilateral pulmonary emboli in a competitive gymnast.

PMID- 20051738
TI  - Sudden death in a young soccer player with marked electrocardiographic
      repolarization abnormalities.

PMID- 20051739
TI  - Cyclists - ulnar nerve and double crush.

PMID- 20051741
TI  - Nonoperative treatment of midportion Achilles tendinopathy: a review.

PMID- 20051742
TI  - Which support for severe ankle sprain promotes fastest functional recovery?

PMID- 20051743
TI  - Interventions to improve patellofemoral pain syndrome: a review.

PMID- 20051744
TI  - Increasing physical activity among older women through exercise prescription.

PMID- 20051745
TI  - Poststreptococcal rheumatic manifestations: an ongoing tale.

PMID- 20051746
TI  - Poststreptococcal reactive arthritis and the association with tendonitis,
      tenosynovitis, and enthesitis.
AB  - AIM: To study the clinical presentation of poststreptococcal reactive arthritis
      (PSRA) and its periarticular manifestation. METHODS: This is a retrospective
      study. The files of all patients diagnosed with PSRA between January 2004 and
      November 2007 were reviewed with a predetermined checklist. Patients were
      included if they met our study criteria for diagnosis of PSRA. RESULTS: A total
      of 33 files were reviewed; 26 of these patients (14 female, 12 male, Arab and
      Asian, aged 11-41 years) met our agreed protocol for the diagnosis of PSRA. The
      ethnic backgrounds of the patients were as follows: 18 patients were from Arab
      origins and 8 patients were Asians. Twenty-one patients (80%) had asymmetric
      complaints, whereas 5 patients (20%) had symmetrical complaints. Two patients
      (7.6%) had monoarthritis, 8 patients (30.76%) had oligoarthritis, and 11 patients
      (42.3%) had polyarthritis. Five patients (19.23%) had only polytendonitis,
      tenosynovitis, and/or enthesitis. Nine patients (34.61%) had tendonitis,
      tenosynovitis, or enthesitis alone or with arthritis/arthralgia. The average
      elevation of antistreptolysin antibodies titer was 624.8 and the average
      sedimentation rate 44 mm/H. The response to nonsteroidal antiinflammatory drugs
      was generally good (84.6%), being poor in only 4 patients (15.38%) who required
      treatment with corticosteroids. Prophylactic penicillin was given to 15 patients
      (57%). No patient had carditis on presentation or follow-up. CONCLUSIONS: It is
      concluded that polytendonitis, tenosynovitis, and enthesitis are common
      presentations in PSRA and could be the only manifestation of poststreptococcal
      infection.

PMID- 20051747
TI  - Calcification of the transverse ligament of the atlas in chondrocalcinosis.
AB  - OBJECTIVE: This study seek to establish the prevalence of calcification of the
      transverse ligament of the atlas (TLA) and of crowned dens syndrome (CDS) in
      patients with articular chondrocalcinosis. It also seeks to assess the main
      computed tomography appearances of these calcifications. PATIENTS AND METHODS:
      Twenty-eight patients with articular chondrocalcinosis were prospectively
      evaluated for evidence of calcifications of the transverse ligament of the atlas.
      A group of patients with gout, fibromyalgia, and osteoarthritis were used as
      control. RESULTS: Twenty-eight patients with articular chondrocalcinosis were
      prospectively evaluated for evidence of calcifications of the transverse ligament
      of the atlas. Twenty of the patients (71%) showed this calcification by computed
      tomography, disclosing 3 patterns of calcification: curvilinear in shape, thick,
      and forming a double band and mottled. Calcifications were not found in the
      controls (P < 0.0001). Nine patients were symptomatic (crowned dens syndrome).
      Patients with chondrocalcinosis and calcification of the transverse ligament of
      the atlas were older than the rest of the patients. Unlike the patient group, the
      majority of the patients in the control group were male (P = 0.02). CONCLUSION:
      The presence of calcifications of the transverse ligament of the atlas in
      patients with chondrocalcinosis occurs more frequently than that reported
      earlier. The CT scan is the most sensitive method to detect it. Taking into
      account that calcifications of TLA may manifest as CDS in a high percentage of
      these patients, such possibility should be considered in all patients with neck
      pain, stiffness, fever, and inflammatory response so as to avoid invasive
      diagnostic methods and more aggressive treatments than the use of nonsteroidal
      anti-inflammatory drugs.

PMID- 20051748
TI  - Vasculitis integrated clinical assessment database: a data management system to
      support studies into systemic vasculitis.
AB  - BACKGROUND: The systemic vasculitides are characterized by immune inflammation
      affecting blood vessels, which can lead to organ and tissue damage. Treatment has
      improved but optimum long-term management still remains unsatisfactory, requiring
      ongoing therapeutic studies. These often base their measures of efficacy on the
      outcome of clinical assessments which include the Birmingham Vasculitis Activity
      Score and the Vasculitis Damage Index. OBJECTIVES: Efficient management of
      assessment data is complex and often hampered by working with time-consuming
      paper-based systems. The Vasculitis Integrated Clinical Assessment Database
      (VICAD) was created to improve the process. METHODS: VICAD was developed using
      Microsoft Access. Visual Basic for Applications and the Data Access Objects
      Application Programming Interface provide the functionality to assist with
      scoring, calculation of results, and storing of data. RESULTS: VICAD is an
      efficient system for managing data. Evaluation of its use showed an improvement
      in the completeness of patient assessments from 77% (paper based: n = 44) to 98%
      (computer based: n = 30). During development clinicians (n = 4) rated it at 8/10
      for its layout and visual presentation and 8/10 for easy to use (intuitiveness
      and navigability). CONCLUSIONS: The development of an integrated and standardized
      system of data collection (VICAD) helps to support clinical decision making
      processes and report findings in a more timely manner. It is available free for
      use and modification under the GNU General Public License. The open source nature
      of VICAD could help to inform the design of other databases where management of
      complex information into important multisystem diseases is needed.

PMID- 20051749
TI  - Anti-TNF-alpha agents are less effective for the treatment of rheumatoid
      arthritis in current smokers.
AB  - OBJECTIVES: To assess if smoking status at the time of commencing an anti-TNF
      alpha agent for rheumatoid arthritis (RA) reduces the likelihood of achieving at
      least a moderate response on the European League Against Rheumatism (EULAR)
      response criteria at 3-month assessment. METHODS: All patients with RA treated
      with their first anti-TNF-alpha agent at the Department of Rheumatology, Derby
      Hospital NHS Trust between April 2001 and October 2008 were included in this
      retrospective case control study. Information about age, gender, disease
      duration, body mass index, smoking status (current smoker, ex-smoker, and
      nonsmoker), comorbidities, oral prednisolone use, and 28 joint 4 variables
      disease activity score (DAS28) at the time of commencing an anti-TNF-alpha agent
      was recorded. Details of rheumatoid factor (RF) and past and present disease
      modifying antirheumatic drugs were recorded. A case control study was carried out
      to examine possible baseline predictors of treatment effects at the 3-month
      assessment. RESULTS: Results were available for 395 patients at 3-month
      assessment. According to the EULAR response criteria 42 patients failed to show
      at least a moderate response. After adjusting for confounders using multivariate
      analysis, current smoking at the time of commencing an anti-TNF-alpha agent
      reduced the chance of achieving at least a moderate response on the EULAR
      response criteria when compared with nonsmokers (aOR [95% CI] 0.20 [0.05-0.83], P
      = 0.03). CONCLUSIONS: RA patients who smoke are less likely to respond to an anti
      TNF-alpha agent.

PMID- 20051750
TI  - Metastasis in the temporal bone mimicking temporal arteritis.
AB  - This report describes a 72-year-old female patient with a previous history of
      cured breast cancer who presented with acute monocular visual disturbances,
      intense unilateral headache, painful temporal artery palpation, high erythrocyte
      sedimentation rate, and pain and weakness of the femoral muscles. These symptoms
      and signs were suggestive of temporal arteritis, but the finding of the temporal
      artery biopsy was negative, and the patient did not respond to corticosteroid
      treatment. Later, whole body bone scintigraphy revealed dissemination of
      malignancy throughout her skeleton including the skull. To our knowledge, this is
      the first report to show that a metastasis in the temporal bone can closely mimic
      temporal arteritis.

PMID- 20051751
TI  - Systemic amyloidosis presenting as chronic diarrhea in a patient with ankylosing
      spondylitis.
AB  - Secondary (AA) amyloidosis is a disease that is caused by systemic deposition of
      amyloid fibrils. Circulating serum amyloid A protein is an acute phase reactant
      and levels are therefore high during inflammatory states. Chronic elevation of
      serum amyloid A levels results in accumulation and deposition in various organs,
      leading to organ dysfunction. Unless the inciting inflammatory state can be
      controlled, the subsequent development of amyloidosis diminishes patient
      survival. We report a case of systemic amyloidosis that presented primarily as
      chronic diarrhea in a patient with ankylosing spondylitis. Unfortunately for the
      patient, the diagnosis of amyloidosis was delayed for years despite encounters
      with multiple physicians. Early medical intervention to control chronic
      inflammation is imperative and could prevent morbidity and mortality related to
      the development of secondary amyloidosis. Consideration of amyloidosis as a
      diagnosis in patients who have chronic uncontrolled inflammatory conditions is
      also important in preventing poor outcomes related to this disease.

PMID- 20051752
TI  - Sarcoidosis in World Trade Center rescue workers presenting with rheumatologic
      manifestations.
AB  - The health consequences of the World Trade Center collapse are unknown, but
      likely to be significant and may take years to fully appreciate. Sarcoidosis is a
      multisystem inflammatory disorder of unknown etiology characterized
      pathologically by noncaseating granulomas. Inciting events, such as infectious
      agents or possible environmental exposures, have been postulated as the source of
      antigen exposure initiating an inflammatory cascade. We describe 2 cases of
      sarcoidosis in rescue workers with significant exposure from the World Trade
      Center collapse, who presented with extrapulmonary rheumatologic manifestations.
      Our first case involved a 33-year-old white New York City man detective found to
      have sarcoidosis following an evaluation of diffuse joint pain. The second case
      involved a 40-year-old African American man, New York City officer, who presented
      with uveitis, and was subsequently diagnosed with sarcoidosis. These 2 cases
      extend the spectrum of disorders resulting from the World Trade Center disaster
      and illustrate the need for clinicians to be aware of the diverse presentations
      of sarcoidosis in this patient population.

PMID- 20051753
TI  - Hydroxychloroquine-induced myopathy.
AB  - A 70-year-old woman with a history of undifferentiated connective tissue disease
      was admitted for work-up of shortness of breath and progressive weakness over the
      course of 1 year. She had been treated with hydroxychloroquine (HCQ) for last 5
      years. Her evaluation revealed diffuse muscle weakness and hyperpigmentation of
      the skin consistent with HCQ deposition, although this did not entirely explain
      the patient's dyspnea. The patient underwent cardiac evaluation because of
      occasional substernal chest pain and persistent elevation in serum troponin I,
      but her ECG and adenosine thallium study did not show any signs of ischemic heart
      disease. The diagnosis of HCQ-induced myopathy was made with electromyography and
      muscle biopsy. HCQ was discontinued, with improvement of the patient's signs and
      symptoms over the course of the next 18 months.We propose that this patient was
      experiencing myocardial toxicity as a consequence of HCQ deposition disease with
      her clinical picture of skeletal muscle myopathy and HCQ deposition in the skin.
      A Medline search yielded several case reports as well as a case series of
      patients with antimalarial-induced myopathy. HCQ-induced myopathy may be less
      recognized because of its presentation with signs, symptoms, and laboratory
      results which suggest other critical diseases. Moreover, this medication is often
      prescribed to treat illnesses whose clinical manifestations may include myopathy.

PMID- 20051754
TI  - Cetuximab in the treatment of rheumatoid arthritis.
AB  - Members of the epidermal growth factor receptor (EGFR) family and their
      associated ligands are commonly expressed by synovial cells, and may be involved
      in the synovial hyperplasia seen in rheumatoid arthritis and its disease
      progression. This family of receptors is also expressed in cancer cells, and EGFR
      targeted therapy is now a mainstay of anticancer therapy. Cetuximab (Erbitux) is
      a monoclonal antibody directed against the EGFR extracellular receptor that has
      received Food and Drug Administration approval for the treatment of colorectal
      cancer as well as head and neck cancer. We report a case of a 61-year-old woman
      with an extensive history of rheumatoid arthritis requiring multiple therapies,
      who experienced a surprising remission of her disease and its symptoms while
      being treated with cetuximab for her head and neck cancer. The case as well as
      possible mechanisms of action are discussed. Further clinical investigations are
      clearly warranted.

PMID- 20051755
TI  - Diffuse muscoskeletal pain and proximal myopathy: do not forget hypovitaminosis
      D.
AB  - A 20-year-old vegetarian man was admitted to our hospital complaining of muscle
      weakness and gait disturbances of 4 years duration. For the past 5 years, he had
      major depression and had confined himself at home. He exhibited tenderness upon
      palpation of the chest, sternum and proximal muscles. Hypocalcemia,
      hypophosphatemia, vitamin D deficiency, increased levels of alkaline phosphatase,
      and intact parathyroid hormone were noted. An x-ray skeletal survey revealed
      generalized osteopenia, multiple vertebral and costal fractures, and a pelvis
      deformed into the shape of a triangle. A diagnosis of osteomalacia secondary to
      vitamin D deficiency from lack of exposure to sunlight and to inadequacy of the
      diet was made. The patient was started on a treatment with 20,000 IU of vitamin
      D3 once a week plus 1 g/d of calcium. Eight months later, gait disturbances have
      significantly improved and laboratory findings have all normalized.

PMID- 20051756
TI  - An atypical presentation of visceral leishmaniasis infection in a patient with
      rheumatoid arthritis treated with infliximab.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a cytokine, implicated in the
      pathogenesis of many inflammatory diseases, as well as in the immune-mediated
      response to infection, especially against intracellular pathogens. TNF-alpha
      antagonists have represented a revolution in the management of connective tissue
      diseases, such as rheumatoid arthritis. However, the use of these agents has been
      implicated with the emergence of a growing number of opportunistic infections.
      Here we report the case of a visceral Leishmaniasis in a 77-year-old woman who
      had been previously treated for rheumatoid arthritis with infliximab. The
      atypical presentation of this patient, previously treated with an anti-TNF-alpha
      biologic agent, where no splenomegaly or hepatomegaly was identified, is
      emphasized.

PMID- 20051757
TI  - Refractory polyarticular gouty arthritis as a manifestation of immune
      reconstitution inflammatory syndrome.
AB  - Immune reconstitution inflammatory syndrome (IRIS) describes the initial clinical
      deterioration some patients manifest upon initiation of effective antiretroviral
      therapy (ART) for HIV infection. In this report we describe a case of IRIS
      manifesting as polyarticular gout, a previously unreported rheumatological
      manifestation of IRIS. A 53-year-old HIV-infected man with a history of
      intermittent attacks of gout and an initial CD4 count of 112 cells/microL and a
      viral load of >100,000 copies/mL presented to our institution with severe,
      refractory, polyarticular gout approximately 4 weeks after initiating ART. At
      this point, the patient demonstrated significant gains in his CD4 counts (103
      cells/microL) and a greater than 3 log decline in his HIV-1- viral load. This
      episode was prolonged lasting for approximately 10 weeks and required
      hospitalization for the management of pain and control of inflammation. The
      temporal associations of this attack with the initiation of ART and the observed
      immunologic reconstitution make IRIS a clinical possibility.Monosodium urate
      crystals through their interactions with interleukin 1- beta, and neutrophilic
      synovitis play a critical role in the pathophysiology of gout. Defects in both
      neutrophil and macrophage function and imbalances in the cytokine milieu are
      documented in HIV infected patients. The introduction of ART results in
      restoration of neutrophil and macrophage function, declines in levels of the anti
      inflammatory cytokine IL-10, and increases in levels of proinflammatory cytokines
      including IL-1 beta, which may provide the necessary milieu for the precipitation
      of attacks of severe polyarticular gout in the context of ART initiation.

PMID- 20051758
TI  - Peritonitis as the primary manifestation at onset of childhood systemic lupus
      erythematosus.

PMID- 20051759
TI  - Achromobacter xylosoxidans presenting as a suprapatellar abscess and
      polyarthritis.

PMID- 20051760
TI  - Dengue mimicking a lupus flare.

PMID- 20051761
TI  - Necrotizing fasciitis caused by Haemophilus influenzae type E in a 17-year-old
      girl with systemic lupus erythematosus.

PMID- 20051762
TI  - Localized osteoporosis and its consequences.

PMID- 20051763
TI  - Tendon sheath gout diagnosed by ultrasound.

PMID- 20051765
TI  - Bone infarctions in a patient with systemic lupus erythematosus and anti
      cardiolipin antibodies.

PMID- 20051768
TI  - Technical and policy approaches to balancing patient privacy and data sharing in
      clinical and translational research.
AB  - INTRODUCTION: Clinical researchers need to share data to support scientific
      validation and information reuse and to comply with a host of regulations and
      directives from funders. Various organizations are constructing informatics
      resources in the form of centralized databases to ensure reuse of data derived
      from sponsored research. The widespread use of such open databases is contingent
      on the protection of patient privacy. METHODS: We review privacy-related problems
      associated with data sharing for clinical research from technical and policy
      perspectives. We investigate existing policies for secondary data sharing and
      privacy requirements in the context of data derived from research and clinical
      settings. In particular, we focus on policies specified by the US National
      Institutes of Health and the Health Insurance Portability and Accountability Act
      and touch on how these policies are related to current and future use of data
      stored in public database archives. We address aspects of data privacy and
      identifiability from a technical, although approachable, perspective and
      summarize how biomedical databanks can be exploited and seemingly anonymous
      records can be reidentified using various resources without hacking into secure
      computer systems. RESULTS: We highlight which clinical and translational data
      features, specified in emerging research models, are potentially vulnerable or
      exploitable. In the process, we recount a recent privacy-related concern
      associated with the publication of aggregate statistics from pooled genome-wide
      association studies that have had a significant impact on the data sharing
      policies of National Institutes of Health-sponsored databanks. CONCLUSION: Based
      on our analysis and observations we provide a list of recommendations that cover
      various technical, legal, and policy mechanisms that open clinical databases can
      adopt to strengthen data privacy protection as they move toward wider deployment
      and adoption.

PMID- 20051769
TI  - Effect of month-long treatment with oral N-acetylcysteine on the oxidative stress
      and proteinuria in patients with diabetic nephropathy: a pilot study.
AB  - INTRODUCTION: Oxidative stress plays an important role in the pathogenesis of
      diabetic nephropathy (DN). This study examined if use of N-acetylcysteine for a
      month in moderate doses would reduce the oxidative stress in patients with DN and
      reduce the proteinuria. METHODS: Fifteen volunteers with DN participated in the
      study. Participants took capsule form of N-acetylcysteine 1 gm twice a day for a
      month. Spot urines were collected and tested for protein/creatinine on days 1 and
      30. Sera were collected on days 1, 15, 30, and 60 and tested for several
      oxidative stress biomarkers. RESULTS: There was no significant change in
      proteinuria or any of the oxidant stress markers at any point: protein-creatinine
      ratio (day 1, 1.6 +/- 1.8; day 30, 1.3 +/- 1.3), 8-isoprostane (day 1, 5.9 +/-
      4.2 pg/mL; day 15, 4.67 +/- 2.4 pg/mL; day 30, 5.1 +/- 2.8 pg/mL; and day 60, 4.7
      +/- 1.9 pg/mL), total antioxidant status (day 1, 1.5 +/- 0.1 mM; day 15, 1.6 +/-
      0.2 mM; day 30, 1.5 +/- 0.1 mM; and day 60, 1.5 +/- 0.2 mM), aconitase (day 1,
      7.9 +/- 5.9 mU/mL; day 15, 10.1 +/- 5.9 mU/mL; day 30, 8.9 +/- 6.2 mU/mL; and day
      60, 7.8 +/- 5.5 mU/mL), glutathione peroxidase (day 1, 261.4 +/- 56.4 mU/mL; day
      15, 263.9 +/- 57.2 mU/mL; day 30, 269.2 +/- 66.0 mU/mL; and day 60, 257.5 +/-
      48.2 mU/mL), and superoxide dismutase (day 1, 242.6 +/- 79.3 mU/mL; day 15, 252.1
      +/- 68.1 mU/mL; day 30, 262.0 +/- 73.3 mU/mL; and day 60, 255.7 +/-
      61.5).However, 4 patients with initial high isoprostane levels showed
      nonsignificant decline at each subsequent time point. CONCLUSIONS: N
      acetylcysteine in moderate doses given over a month did not have significant
      effect on the overall oxidative stress in patients with DN and did not reduce
      proteinuria.

PMID- 20051771
TI  - Pediatric lymphoma: a 10-year experience at a tertiary care hospital in Pakistan.
AB  - SUMMARY: Lymphoma is the third most common childhood malignancy. Less information
      is available on this disease and its outcome from our country. We present here a
      single institute experience. A retrospective study was carried out at Aga Khan
      University Hospital, Karachi on children (<15 y) diagnosed with lymphoma from
      1998 to 2007. Sixty-eight patients were identified. Fifty-one children were
      diagnosed as non-Hodgkin lymphoma (NHL). Mean age of presentation was 8.4 years
      with male-to-female ratio of 5.8 : 1. Most common histopathologic subtype of NHL
      was Burkitt lymphoma (55%). Abdominal mass was the main presenting feature of
      Burkitt and diffuse large B cell lymphoma. T-lymphoblastic lymphoma presented
      mainly as mediastinal mass. Ten children died, 4 secondary to tumor lysis
      syndrome, 5 because of disease progression, and 1 with chemotherapy-induced
      toxicity. One-third of the patients left without treatment. Seventeen children
      were diagnosed as Hodgkin lymphoma with mixed cellularity as the commonest
      subtype (65%). Overall survival of children with NHL and Hodgkin lymphoma was 62%
      and 94%, respectively. A greater proportion of NHL, advanced stage, and profound
      male preponderance were observed. Improvement in survival can only be achieved
      with increasing awareness, identifying and tackling causes of abandonment, early
      referral, and better supportive care.

PMID- 20051772
TI  - Successful management of a simultaneous Aspergillus fumigatus and Absidia
      corymbifera invasive fungal infection.
AB  - SUMMARY: Considering the poor prognosis of pediatric patients with invasive
      fungal infections due to zygomycosis, we present the case of a female adolescent
      with acute lymphoblastic leukemia, who successfully completed her chemotherapy
      despite a disseminated double infection with Aspergillus fumigatus and Absidia
      corymbifera.

PMID- 20051773
TI  - Idiopathic thrombocytopenic purpura in a boy with ataxia telangiectasia on
      immunoglobulin replacement therapy.
AB  - Ataxia telangiectasia (AT) is an inherited cerebellar degeneration syndrome often
      associated with immune deficiency, notably, lymphopenia, hypogammaglobulinemia,
      and cellular immune dysfunction. Although autoimmunity is a common feature of
      many congenital and acquired immune deficiencies, it has not generally been
      thought to be associated with AT. We report a 7-year-old boy with AT who
      developed acute idiopathic thrombocytopenic purpura while on subcutaneous
      immunoglobulin replacement therapy for hypogammaglobulinemia. He responded
      promptly to high-dose intravenous immunoglobulin. This case reinforces the notion
      that one must be observant for autoimmune hematologic conditions in any child
      with qualitative or quantitative deficiencies in cellular immunity.

PMID- 20051774
TI  - Ataxia-telangiectasia with hyper-IgM and Wilms tumor: fatal reaction to
      irradiation.
AB  - SUMMARY: Ataxia-telangiectasia is an autosomal recessive disorder caused by
      mutation in the ATM gene. Hallmarks of the disease comprise progressive
      cerebellar ataxia, oculocutaneous telangiectasiae, cancer susceptibility, and
      variable humoral and cellular immunodeficiency. We report a patient who, because
      of the pattern of her immunodeficiency, was primarily diagnosed as an autosomal
      recessive hyper-IgM syndrome. Only a mild cerebellar ataxia was present at the
      age of 7 years then she developed a Wilms tumor (nephroblastoma). Conventional
      radiotherapy for the malignancy led to fatal consequences. Postmortem studies
      confirmed diagnosis of ataxia-telangiectasia.

PMID- 20051775
TI  - Adoptive transfer of cytomegalovirus/Epstein-Barr virus-specific immune effector
      cells for therapeutic and preventive/preemptive treatment of pediatric allogeneic
      cell transplant recipients.
AB  - SUMMARY: This report describes a safe and effective therapy through adoptive
      transfer of donor cytomegalovirus (CMV)/Epstein-Barr virus (EBV) immune effector
      cells. The patients, from 3 to 10 years of age, suffering from hematologic
      diseases received haploidentical transplantation. All 3 patients developed
      varying levels of viremia from days 13 to 31 and 2 patients developed CMV
      interstitial pneumonitis or interstitial inflammation after transplantation.
      Tapering down the dose of immunosuppressives together with intensive antivirus
      therapy and escalated infusions of donor-derived CMV/EBV immune effector cells
      effectively controlled virus-related diseases. All 3 patients survived and
      remained CMV/EBV-free 14-16 months after transplantation.

PMID- 20051776
TI  - Spinal myxopapillary ependymoma with Down syndrome: exploring an unusual
      association.
AB  - SUMMARY: In patients with Down syndrome, cancers like leukemia and testicular
      tumors are frequent, but association with central nervous system tumors is rare.
      Only 1 case of ependymoma has been observed as an incidental autopsy finding in a
      19-week-old female fetus. We herein report the second case of ependymoma and the
      fifth case of spinal tumor occurring in association with Down syndrome. We have
      also attempted to elucidate the various mechanisms of tumorigenesis implicated in
      this multiple malformation syndrome. A 13-year-old girl with Down syndrome
      presented with progressively increasing paraparesis and neurogenic bladder.
      Magnetic resonance imaging of dorsolumbar spine revealed an intramedullary mass
      (L1 to L5 level). The patient underwent near total excision of tumor with
      postoperative histopathology showing myxopapillary ependymoma. Karyotyping showed
      classic Down syndrome with trisomy 21. Postoperative irradiation (45 Gy in 25
      fractions over 5 wk followed by boost up to 55 Gy) was subsequently delivered.
      One year after the completion of the tumor-directed therapy, the patient is in
      radiologic complete remission, with improved power in both lower limbs.
      Association of ependymoma with Down syndrome is a rarity, which at best, can be
      explained as a chance phenomenon.

PMID- 20051778
TI  - CALLA and protein kinase CK2 revisited: targetable molecules for treating
      patients with leukemia?

PMID- 20051777
TI  - Serial plasma concentrations of adiponectin, leptin, and resistin during therapy
      in children with acute lymphoblastic leukemia.
AB  - PURPOSE: To investigate adipocytokine secretion, at diagnosis and during
      chemotherapy in children with the acute lymphoblastic leukemia (ALL). PATIENTS
      AND METHODS: Serial measurements (6/patient) of the anti-inflammatory cytokine
      adiponectin and the proinflammatory adipocytokines leptin and resistin were
      performed at diagnosis and in nearly the entire period of therapy (up to 21
      months), in 9 patients with ALL aged 2 to 7 years (median 4.3 y). Body mass index
      and leukemic burden were estimated at the same time points and correlated with
      adipocytokine levels. Nine healthy children matched for age, sex, and body mass
      index were used as controls. RESULTS: At diagnosis, mean adiponectin levels were
      low (P<0.001) and mean leptin and resistin levels were high, compared with
      controls (P<0.001). During maintenance phase, adiponectin increased significantly
      (P=0.024), whereas leptin and resistin decreased (P=0.018 and P=0.020,
      respectively), compared with baseline values. However, adiponectin, despite its
      progressive increase, remained at lower levels toward the end of the maintenance
      phase, compared with controls, (P<0.001). Delta (final-baseline) mean adiponectin
      was negatively correlated with leukemic burden (P=0.019), whereas delta mean
      leptin and resistin were positively correlated with it (P=0.011 and P=0.031,
      respectively). CONCLUSIONS: Low-plasma adiponectin and high leptin and resistin
      level are present at the ALL diagnosis. Adipocytokines alterations are
      progressively restored during therapy.

PMID- 20051779
TI  - Is methylation the key to CD10 loss?

PMID- 20051780
TI  - Dense methylation of types 1 and 2 regulatory regions of the CD10 gene promoter
      in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene.
AB  - SUMMARY: Infant acute lymphoblastic leukemia (ALL) displays distinct biologic and
      clinical features with a poor prognosis. The CD10-negative immunophenotype of
      infant ALL is a hallmark and provides a predictable signature of mixed-lineage
      leukemia (MLL) rearrangement. Although CD10 negativity reflects an earlier stage
      of B-cell development, complete IgH gene rearrangements (VDJH), found in almost
      half of the patients, show more mature IgH status. Discordance between
      immunophenotype and genotype of infant ALL suggests an aberrant process in
      immunophenotypic steps of differentiation or a secondary down-regulation of CD10
      expression. In this study, CD10-negative infant ALL with MLL/AF4, CD10-positive
      infant ALL with germline MLL, CD10-positive pre-B ALL cell line, infant acute
      myeloid leukemia (AML; M5) with MLL/AF9 and pediatric AML (M2) with AML1/ETO were
      analyzed for VDJH status and methylation of CD10 gene promoters. Three of the 4
      infant ALL samples showed complete rearrangements of the VDJH gene with
      productive joints. Bisulfite sequencing of CD10 type 1 and 2 promoters showed
      that more than 84% of the cytosine-phosphate-guanine (CpG) dinucleotides
      identified were methylated in all 3 CD10-negative infant ALL samples with
      MLL/AF4. The CpG dinucleotides distributed in the clusters of putative Sp1
      binding sites and functionally active regulatory regions of the promoters were
      fully methylated. In contrast, none of the CpG dinucleotides were methylated in
      the CD10-positive ALL samples. Structural evidence of dense methylation in the
      CD10 gene promoter suggested that methylated transcription factor binding sites
      contribute to CD10 silencing as an epigenetic mechanism.

PMID- 20051781
TI  - Clinical characteristics of G6PD deficiency in infants with marked
      hyperbilirubinemia.
AB  - SUMMARY: This study analyzes the clinical features of glucose-6-phosphate
      dehydrogenase (G6PD) deficiency in infants with marked hyperbilirubinemia. We
      retrospectively assessed a cohort of 413 infants with peak total serum bilirubin
      (TSB) level >or=20 mg/dL from 1995 to 2007. The prevalence of G6PD deficiency was
      proportional to the level of peak TSB: 21.1% (81/383) in 20 mg/dL to 29.9 mg/dL,
      45.5% (10/22) in 30 mg/dL to 39.9 mg/dL, and 100% (8/8) in >or=40 mg/dL. Male sex
      was more common in G6PD deficiency (75.8%). When compared with G6PD-normal
      infants, those with G6PD deficiency tended to have extreme hyperbilirubinemia
      (peak TSB level >or=25 mg/dL) and hemoglobin value<13 g/dL (P<0.001).
      Furthermore, mortality rate was significantly higher in G6PD-deficient infants
      (3.0%) than in the G6PD-normal counterparts (0.0%). Among 58 of the G6PD
      deficient infants who were followed for more than 12 months, 4 developed the
      classic neurologic manifestations of kernicterus (6.6%). These findings show that
      G6PD deficiency is an important risk factor of extreme hyperbilirubinemia, death,
      and kernicterus.

PMID- 20051782
TI  - Glyceraldehyde-3-phosphate dehydrogenase expression is altered by hypoxia in
      melanoma cells and primary human melanocytes.

PMID- 20051783
TI  - The initiation and progression of melanoma: estrogens or estrogen receptors?

PMID- 20051784
TI  - Functional MRI reveals expert-novice differences during sport-related
      anticipation.
AB  - We examined the effect of expertise on cortical activation during sports
      anticipation using functional MRI. In experiment 1, recreational players
      predicted badminton stroke direction and the pattern of active clusters was
      consistent with a proposed perception-of-action network. This pattern was not
      replicated in a stimulus-matched, action-unrelated control task. In experiment 2,
      players of three different skill levels anticipated stroke direction from clips
      occluded either 160 ms before or 80 ms after racquet-shuttle contact. Early
      occluded sequences produced more activation than late-occluded sequences overall,
      in most cortical regions of interest, but experts showed an additional
      enhancement in medial, dorsolateral and ventrolateral frontal cortex.
      Anticipation in open-skill sports engages cortical areas integral to observing
      and understanding others' actions; such activity is enhanced in experts.

PMID- 20051785
TI  - Withdrawal from multiple sedative agent therapy in an infant: is dexmedetomidine
      the cause or the cure?
AB  - OBJECTIVE: To report withdrawal symptoms experienced by an infant following the
      prolonged use of dexmedetomidine. DESIGN: Case report. SETTING: Pediatric
      intensive care unit at a freestanding tertiary care children's hospital.
      PATIENTS: One pediatric patient with respiratory failure following pertussis
      infection that required prolonged intubation and sedation. The patient required
      dexmedetomidine to maintain optimal sedation before ventilator weaning.
      Subsequent to receiving dexmedetomidine the patient developed withdrawal
      symptoms. CONCLUSION: In patients who fail to achieve adequate sedation with the
      use of traditional medications, dexmedetomidine is an adequate alternative.
      However, abrupt discontinuation of dexmedetomidine may result in withdrawal
      symptoms that may be avoided with a dexmedetomidine taper.

PMID- 20051786
TI  - Occlusive aortic arch thrombus in a preterm neonate.
AB  - OBJECTIVE: To present the case of an extremely preterm infant with occlusive
      aortic arch clot managed with low-risk therapy. DATA SOURCE: Case details were
      obtained from medical records and echocardiographic images from Excelera
      database. STUDY SELECTION: Preterm infant with occlusive clot in the aortic arch.
      DATA EXTRACTION AND SYNTHESIS: Demographic details (gestation age and
      birthweight), clinical and biochemical data (blood pressure, oxygen saturation,
      urine output, lactate levels, and coagulation profile) were obtained from medical
      records. A female infant was born at 28 wks gestation and had umbilical catheters
      inserted in satisfactory positions. On day 6, pre- and postductal oxygen
      saturation differences, a significantly higher blood pressure on right arm, and
      weak pulses were noted. Echocardiogram revealed an occlusive thrombus in the
      aortic arch distal to the innominate artery, extending into the carotid artery
      with retrograde flow in the left internal carotid and subclavian arteries. The
      distal aortic circulation was supported by ductus arteriosus shunting
      bidirectionally. Intravenous prostaglandin E and heparin were started, the latter
      was later replaced by enoxaparin. Serial echocardiograms over next 3 mos showed
      complete resolution of the thrombus. CONCLUSIONS: Neonatal aortic arch thrombus
      is extremely rare with only 3 cases previously reported--all in term infants.
      Therapeutic options include anticoagulation, thrombolytic therapy, and
      thrombectomy. The risk/benefit ratio for anticoagulation and thrombolytic therapy
      is unknown and must be individualized. This preterm infant was managed with low
      risk therapy and had an optimal outcome.

PMID- 20051787
TI  - Severe pulmonary hypertension associated with the acute motor sensory axonal
      neuropathy subtype of Guillain-Barre syndrome.
AB  - OBJECTIVE: To evaluate pulmonary hypertension associated with acute motor sensory
      axonal neuropathy subtype of Guillain-Barre syndrome. Guillain-Barre syndrome
      consists of a group of autoimmune disorders that generally manifest as symmetric,
      progressive, ascending paralysis. There are five subtypes of Guillain-Barre
      syndrome, and autonomic involvement has been described in all subtypes, including
      cardiovascular, vasomotor, or pseudomotor dysfunction of both the sympathetic and
      parasympathetic systems. DESIGN: Case report. SETTING: Tertiary care pediatric
      intensive care unit. PATIENT: Three-yr-old female patient. INTERVENTION: None.
      MEASUREMENTS AND MAIN RESULTS: Serial measurements of pulmonary artery pressure.
      We report the case of a young girl with acute motor sensory axonal neuropathy who
      presented with severe cardiovascular collapse secondary to severe pulmonary
      hypertension. In this patient, multiple factors may have played a role in the
      development of pulmonary hypertension including autonomic dysfunction,
      hypoventilation, and immobility as a risk for thrombosis and pulmonary emboli.
      CONCLUSION: It is possible that many other individuals suffering from severe
      forms of Guillain-Barre syndrome, especially those with significant autonomic
      dysfunction, may actually have undiagnosed and therefore untreated pulmonary
      hypertension. Therefore, it is recommended that clinicians caring for critically
      ill children with Guillain-Barre syndrome have a high index of suspicion for
      pulmonary hypertension and consider echocardiography if there are clinical signs
      of this potentially fatal process.

PMID- 20051788
TI  - Successful use of extracorporeal life support in a hematopoietic stem cell
      transplant patient with diffuse alveolar hemorrhage.
AB  - OBJECTIVE: To describe the successful use of extracorporeal life support in a
      hematopoietic stem cell transplant patient with diffuse alveolar hemorrhage.
      DESIGN: Case report. SETTING: Pediatric intensive care unit in a freestanding
      quaternary children's hospital. PATIENT: A 20-mo-old male with Hurler syndrome
      who developed respiratory failure from diffuse alveolar hemorrhage after
      hematopoietic stem cell transplant and was managed successfully with
      extracorporeal life support. INTERVENTION: Placement on extracorporeal membrane
      oxygenation. MEASUREMENTS AND MAIN RESULTS: Diffuse alveolar hemorrhage is a well
      known complication in hematopoietic stem cell transplant patients, with an even
      higher occurrence in those with Hurler syndrome. Extracorporeal membrane
      oxygenation has been contraindicated traditionally in both pulmonary hemorrhage
      and hematopoietic stem cell transplant patients. We report the successful use of
      extracorporeal membrane oxygenation and survival to hospital discharge in a
      hematopoietic stem cell transplant patient with diffuse alveolar hemorrhage.
      CONCLUSION: Although the reported survival of hematopoietic stem cell transplant
      patients on extracorporeal membrane oxygenation remains low, each patient must be
      evaluated for potential benefit of extracorporeal life support.

PMID- 20051789
TI  - Noninvasive ventilation and low-flow veno-venous extracorporeal carbon dioxide
      removal as a bridge to lung transplantation in a child with refractory
      hypercapnic respiratory failure due to bronchiolitis obliterans.
AB  - OBJECTIVE: To report the successful management of end-stage hypercapnic
      respiratory failure through the association of noninvasive mechanical ventilation
      and a novel automated device (Decapsmart) of low-flow veno-venous extracorporeal
      CO2 removal. DESIGN: Case report. SETTINGS: Pediatric intensive care unit at a
      tertiary care children's hospital. PATIENT: A pediatric patient affected by
      bronchiolitis obliterans with refractory hypercapnic respiratory failure. The
      patient received successful lung transplantation after respiratory support with
      noninvasive mechanical ventilation and a novel automated device of low-flow veno
      venous extracorporeal CO2 removal. INTERVENTIONS: Treatment of end-stage
      hypercapnic respiratory failure with the association of noninvasive ventilation
      and low-flow veno-venous extracorporeal CO2 removal as a bridge to lung
      transplantation. MEASUREMENTS AND MAIN RESULTS: Respiratory support controlling
      hypercapnia, limiting volutrauma, barotraumas, and preventing the incidence of
      ventilator-associated pneumonia/lung colonization. CONCLUSION: Noninvasive
      mechanical ventilation and Decapsmart have proven efficacious in managing
      refractory hypercapnic respiratory failure in a pediatric patient awaiting lung
      transplantation.

PMID- 20051791
TI  - Synchronizing ventilatory support with the neural signal to breathe.

PMID- 20051792
TI  - SpO2/Fio2 vs PaO2/Fio2: are we ready to establish less invasive indicators for
      early diagnosis of acute respiratory distress syndrome?

PMID- 20051793
TI  - Somatotropic axis dysfunction in pediatric sepsis-induced multiple organ
      dysfunction syndrome . . . a matter of "growing" importance!

PMID- 20051794
TI  - Early decannulation of the pediatric patient from tracheostomy to noninvasive
      positive pressure ventilation: teamwork and patience.

PMID- 20051795
TI  - Dexmedetomidine and pediatric (cardiac) critical care--are we there yet?

PMID- 20051796
TI  - Is cardiac surgery sufficient to create insufficiency?

PMID- 20051797
TI  - Therapeutic hypothermia and pediatric cardiac arrests: vexing questions.

PMID- 20051798
TI  - Systemic inflammatory response syndrome and bacteremia in developing countries.

PMID- 20051799
TI  - Activated recombinant factor VII and extracorporeal membrane oxygenation:
      everything is all right, nothing is wrong?

PMID- 20051800
TI  - Cytokines and hypothermia: harmful or helpful?

PMID- 20051801
TI  - Dexmedetomidine: are tolerance and withdrawal going to be an issue with long-term
      infusions?.

PMID- 20051802
TI  - Extracorporeal lung assistance: the ultimate gentle lung ventilation strategy?

PMID- 20051803
TI  - Management of hyperglycemia in the pediatric intensive care unit.

PMID- 20051805
TI  - Resistance profile of etravirine: combined analysis of baseline genotypic and
      phenotypic data from the randomized, controlled Phase III clinical studies.
AB  - OBJECTIVE: To refine the genotypic and phenotypic correlates of response to the
      nonnucleoside reverse transcriptase inhibitor etravirine. DESIGN: Initial
      analyses identified 13 etravirine resistance-associated mutations (RAMs) and
      clinical cutoffs (CCOs) for etravirine. A multivariate analysis was performed to
      refine the initial etravirine RAM list and improve the predictive value of
      genotypic resistance testing with regard to virologic response and relationship
      to phenotypic data. METHODS: Week 24 data were pooled from the phase III studies
      with TMC125 to Demonstrate Undetectable viral load in patients Experienced with
      ARV Therapy (DUET). The effect of baseline resistance to etravirine on virologic
      response (<50 HIV-1 RNA copies/ml) was studied in patients not using de-novo
      enfuvirtide and excluding discontinuations for reasons other than virologic
      failure (n = 406). Clinical cutoffs for etravirine were established by analysis
      of covariance models and sliding fold change in 50% effective concentration
      (EC50) windows (Antivirogram; Virco BVBA, Mechelen, Belgium). Etravirine RAMs
      were identified as those associated with decreased virologic response/increased
      etravirine fold change in EC50. Relative weight factors were assigned to the
      etravirine RAMs using random forest and linear modeling techniques. RESULTS:
      Baseline etravirine fold change in EC50 predicted virologic response at week 24,
      with lower and preliminary upper clinical cutoffs of 3.0 and 13.0, respectively.
      A fold change in EC50 value above which etravirine provided little or no
      additional efficacy benefit could not be established. Seventeen etravirine RAMs
      were identified and attributed a relative weight factor accounting for the
      differential impact on etravirine fold change in EC50. Virologic response was a
      function of etravirine-weighted genotypic score. CONCLUSION: The weighted
      genotypic scoring algorithm optimizes resistance interpretations for etravirine
      and guides treatment decisions regarding its use in treatment-experienced
      patients.

PMID- 20051806
TI  - Changes in HIV prevalence among differently educated groups in Tanzania between
      2003 and 2007.
AB  - OBJECTIVE: HIV prevalence trends suggest that the epidemic is stable or declining
      in many sub-Saharan African countries. However, trends might differ between
      socioeconomic groups. Educational attainment is a common measure of socioeconomic
      position in HIV datasets from Africa. Several studies have shown higher HIV
      prevalence among more educated groups, but this may change over time. We describe
      changes in HIV prevalence by educational attainment in Tanzania from 2003 to
      2007. DESIGN AND METHODS: Analysis of data from two large, nationally
      representative HIV prevalence surveys conducted among adults aged 15-49 years in
      Tanzania in 2003-2004 (10 934 participants) and 2007-2008 (15 542 participants).
      We explored whether changes in HIV prevalence differed between groups with
      different levels of educational attainment after adjustment for potential
      confounding factors (sex, age, urban/rural residence and household wealth).
      RESULTS: Changes in HIV prevalence differed by educational attainment level
      (interaction test P value = 0.07). HIV prevalence was stable among those with no
      education (adjusted odds ratio 2007-2008 vs. 2003-2004 1.03, 95% confidence
      interval 0.72-1.47), whereas showing a small but borderline significant decline
      among those with primary education (adjusted odds ratio 0.85, 95% confidence
      interval 0.69-1.03) and a larger statistically significant decline among those
      with secondary education (adjusted odds ratio 0.53, 95% confidence interval 0.34
      0.84). DISCUSSION: Prevalent HIV infections are now concentrating among those
      with the lowest levels of education in Tanzania. Although HIV-related mortality,
      migration and cohort effects might contribute to this, different HIV incidence by
      educational level between the surveys provides the most likely explanation.
      Urgent measures to improve HIV prevention among those with limited education and
      of low socioeconomic position are necessary in Tanzania.

PMID- 20051808
TI  - A surveillance, epidemiology, and end results registry analysis of prostate
      cancer modality time trends by age.
AB  - OBJECTIVE: To use the Surveillance, Epidemiology, and End Results (SEER) registry
      to analyze age-specific time trends in the use of radiotherapy (RT) (external
      beam radiotherapy [EBRT], brachytherapy [brachy], and combination therapy
      [combo]) as first-line treatment for prostate cancer. METHODS: A total of 820,649
      prostate cancer patients in the SEER public-use registry (1973-2004) with
      diagnosis year, treatment, and age information available were identified.
      Modality use time-trend curves were plotted for patients 45 to 85+ years of age,
      grouped in 5-year intervals. A nonparametric (Spearman) test was used to assess
      the correlation between diagnosis year and (a) percentage use of RT and (b)
      relative percentage use of EBRT, brachy, and combo therapy. RESULTS: Over the
      study period from 1973 to 2004, RT use increased in patients >=65 years of age,
      but has remained stable in patients <65 years of age. All age groups experienced
      a similar relative rise in the use of brachy and combo therapy, with brachy use
      surpassing combo use in approximately year 2000. CONCLUSIONS: Trends in treatment
      choice for early prostate cancer generally reflect treatment advances, but do not
      appear to be uniform among all age groups. The SEER database is a valuable asset
      for analyzing these trends and can be used to investigate age-specific treatment
      patterns.

PMID- 20051807
TI  - Understanding pathogenetic aspects and clinical presentation of primary effusion
      lymphoma through its derived cell lines.
AB  - Primary effusion lymphoma (PEL) is a very rare subgroup of B-cell lymphomas
      presenting as pleural, peritoneal and pericardial neoplastic effusions in the
      absence of a solid tumor mass or recognizable nodal involvement. There is strong
      evidence that Kaposi's sarcoma-associated herpesvirus (KSHV) is a causal agent of
      PEL. PEL tumor cells are latently infected by KSHV with consistent expression of
      several viral proteins and microRNAs that can affect cellular proliferation,
      differentiation and survival. The most relevant data on pathogenesis and biology
      of KSHV have been provided by studies on PEL-derived cell lines. Fourteen
      continuous cell lines have been established from the malignant effusions of
      patients with AIDS-associated and non-AIDS-associated PEL. These KSHV+ EBV+/-
      cell lines are well characterized, authenticated and mostly available from public
      biological resource centers. The PEL cell lines display unique features and are
      clearly distinct from other lymphoma cell lines. PEL cell lines represent an
      indispensable tool for the understanding of KSHV biology and its impact on the
      clinical manifestation of PEL. Studies on PEL cell lines have shown that a number
      of viral genes, expressed during latency or lytic life cycle, have effects on
      cell binding, proliferation, angiogenesis and inflammation. Also, PEL cell lines
      are important model systems for the study of the disorder of PEL including the
      lack of invasive or destructive growth patterns and the peculiar propensity of
      PEL to involve body cavity surfaces.

PMID- 20051809
TI  - Effectiveness of three-dimensional conformal radiotherapy for treating early
      primary nasopharyngeal carcinoma.
AB  - OBJECTIVE: In 2-dimensional radiotherapy, the irradiating portal is defined
      mainly by soft tissues and bony structures, so the exact location of
      nasopharyngeal tumors and many spatial relationships are unknown, resulting in
      high local-regional relapse rates and radiation toxicities. Three-dimensional
      conformal radiotherapy (3D CRT) provides more precise targeting of radiation. We
      studied whether 3D CRT could maintain survival and increase local-regional tumor
      control whereas reducing the morbidity and severity of radiation toxicity in
      patients with early primary nasopharyngeal carcinoma (NPC). METHODS: Patients
      with histologically proven keratinizing or nonkeratinizing undifferentiated NPC
      (T1-2N0-1M0 stage) received a prescribed 3D CRT dose of 70 Gy to the gross tumor
      volume (GTV(nx)), 60 Gy to the GTV(nx) with an additional 5- to 10-mm margin
      (CTV(nx)60), 60 to 70 Gy to the region involved by the metastatic lymph nodes
      (GTV(nd)), and 50 Gy to the prophylactic irradiating region (CTV(nd)50). RESULTS:
      Of 58 patients enrolled between August 2001 and December 2006, (48 men; median
      age, 46 years; range, 29-69 years), 15 had stage I and 43 had stage II disease.
      At 5 years, overall survival was 95% and disease-free survival was 91%; 93% of
      patients were free of local-regional recurrence and 98% were free of distant
      metastases. Grade 2 or 3 xerostomia occurred in 7 patients and trismus occurred
      in 5. Mean standard deviation (SD) dental gap was 37.4 (6.9) mm. Four patients
      had recurrent lesions, mainly in-field. CONCLUSIONS: The survival and morbidity
      provided by 3D CRT were excellent in these patients with early NPC.

PMID- 20051810
TI  - Identifying subsets of metastatic breast cancer patients likely to benefit from
      treatment with the epothilone B analog ixabepilone.
AB  - Breast cancer consists of a heterogeneous group of diseases, with a number of
      tumor-specific and patient-specific factors, which influence response to therapy
      and survival. Ixabepilone is a member of a novel class of antineoplastic agents,
      the epothilones, that has demonstrated activity in a number of human solid tumor
      types and is the first agent in this class to be approved by the Food and Drug
      Administration (FDA) for the treatment of metastatic or locally advanced breast
      cancer, that is resistant/refractory to anthracyclines, taxanes, and/or
      capecitabine. Both retrospective and prospective studies have been conducted to
      evaluate the efficacy of ixabepilone in various populations. The role of
      ixabepilone in poor prognosis subgroups of the metastatic breast cancer
      population is reviewed in this article.

PMID- 20051811
TI  - Cost comparison of capecitabine in patients with breast cancer.
AB  - OBJECTIVE: Capecitabine may have a higher acquisition cost compared with other
      select chemotherapy agents; however, its use is not associated with many of the
      costs typically encountered with intravenous chemotherapy, such as costs incurred
      through administration procedures and the management of subsequent tolerability
      issues. This study compared the cost of capecitabine- and taxane-based regimens
      in the treatment of breast cancer. STUDY DESIGN: Thomson Reuters MarketScan, a US
      employer claims database, was used to identify patients with a breast cancer
      diagnosis between 2000 and 2005 and at least one chemotherapy claim or hormone
      treatment in 2004 or 2005. METHODS: Cost data for treatment administration and
      management of selected chemotherapy-related adverse events were collected.
      Multivariate analyses were performed to adjust for differences in patient
      demographic and clinical factors. RESULTS: A total of 3630 patients were included
      in this analysis; 4216 treatment episodes were recorded. Mean unadjusted total
      monthly expenditures were lowest for capecitabine regimens compared with taxane
      plus anthracycline or other taxane regimens ($8445 vs. $13,295 and $12,323,
      respectively; P < 0.0001). The adjusted total monthly cost for capecitabine
      regimens was lower than the cost for taxane plus anthracycline regimen ($10,895
      vs. $13,115) and other taxane regimens ($9253 vs. $12,116). Adjusted complication
      costs for taxane treatment episodes were almost double than those seen with
      capecitabine ($5509 for anthracycline plus taxane vs. $2940, and $3829 for other
      taxane regimens vs. $1750). CONCLUSIONS: Lower complication-related expenditures
      with capecitabine therapy accounted for majority of the cost differential seen in
      comparison with taxane-based therapy.

PMID- 20051812
TI  - Radiation therapy for management of t1-t2 glottic cancer at a private practice.
AB  - PURPOSE: The purpose of this study was to retrospectively analyze patients with
      T1-T2N0 squamous cell carcinomas of the glottic larynx treated at a private
      institution, to review the pertinent literature, and to compare our outcomes to
      those of academic institutions. METHODS AND MATERIALS: A total of 118 patients
      were treated with radiation therapy between May 1987 and August 2006 at a private
      institution and followed up for >=2 years. Three patients were lost to follow-up
      between 18 and 19 months. RESULTS: The 5-year local control rates were: T1a, 91%;
      T1b, 95%; T2a, 96%; and T2b, 100%. The 5-year ultimate local control rates after
      irradiation and including patients who were successfully salvaged with surgery
      after a local recurrence were: T1a, 94%; T1b, 100%; T2a, 96%; and T2b, 100%.
      Eight (7%) of the 118 patients developed a local recurrence. There were no
      isolated regional or distant recurrences. The 5-year overall survival rates were:
      T1a, 73%; T1b, 78%; T2a, 62%; and T2b, 69%. The 5-year cause-specific survival
      rates were: T1a, 96%; T1b, 100%; T2a, 100%; and T2b, 100%. Two patients
      experienced severe complications. CONCLUSION: Patients with limited T1aN0 cancers
      may be treated with either transoral laser excision or RT. Those with more
      advanced T1-T2N0 cancers are treated with definitive RT. We do not advocate
      elective nodal irradiation, even for those with bulky T2B malignancies. The
      addition of concomitant weekly cisplatin 30 mg/M2 is considered for patients with
      T2B cancers. Open parotid laryngectomy is reserved for salvage of suitable
      patients with a local recurrence.

PMID- 20051813
TI  - Polyploidy in spitz nevi: a not uncommon karyotypic abnormality identifiable by
      fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) often reveals imbalanced chromosomal
      gains in melanoma, whereas Spitz nevi typically have a normal complement of
      chromosomes. However, there may be a subset of Spitz nevi that are perfectly
      tetraploid by FISH analysis, and these cases may be confused diagnostically with
      melanoma. This study evaluates 41 cases of Spitz nevi that were histologically
      confirmed to be benign. Four of these lesions demonstrated polyploidy by FISH.
      Three of the 4 cases were from the same patient, a 17-year-old woman; 1 lesion
      was from the wrist, whereas the other 2 were from the buttocks. The other case
      was from a 14-year-old man from the ankle. All 4 cases that were polyploid were
      confirmed using a probe for the X chromosome. This article highlights the
      importance of polyploidy as a feature of some benign Spitz nevi.

PMID- 20051814
TI  - Immunohistochemical study of the expression of matrix metalloproteinase-9 in skin
      lesions of mycosis fungoides.
AB  - Matrix metalloproteinase-9 (MMP-9) has been correlated with poor clinical outcome
      in various malignancies and is associated with enhanced tumor growth and
      dissemination through its role in angiogenesis. This study was carried out to
      review the immunohistological staining of MMP-9 in skin lesions of different
      stages of mycosis fungoides (MF). The study was carried on 22 patients with MF
      and 10 healthy controls. Immunohistochemical staining using MMP-9 monoclonal anti
      human antibodies was performed to determine the intensity of expression and
      distribution pattern of MMP-9 in MF lesions and in normal control skin. The
      general intensity of expression of MMP-9 was found to be significantly higher in
      cases with MF than in controls, and it increased in direct proportion to the
      increase in disease severity, being greatest in the tumor stages. A significantly
      greater number of blood vessels were found in cases with MF when compared with
      controls, and the MMP-9 expression by endothelial cells was significantly higher
      in endothelial cells within tumor cell aggregates than in endothelial cells
      outside the tumor cell aggregates. This study raises the possibility that MMP-9
      may play an important role in the development of MF lesions, and its
      significantly higher expression in tumor stages may point to a possible role in
      disease progression. Further studies are needed to validate these findings and to
      assess the possible therapeutic role of drugs targeting MMP-9 in the treatment of
      MF.

PMID- 20051815
TI  - The role of immunohistochemistry in discriminating primary from secondary
      extramammary Paget disease.
AB  - BACKGROUND: Extramammary Paget disease (EMPD) is categorized into 2 groups:
      primary EMPD or EMPD secondary to underlying malignancy. Primary EMPD has a
      better prognosis, and the ability to distinguish between the 2 subsets has
      clinical relevance. Recent studies have suggested that immunostains, including
      cytokeratin (CK) 7, CK20, and BRST-2, distinguish between the 2 groups. We
      analyzed a large series of EMPD with an expanded immunohistochemical panel to
      assess its value in distinguishing primary from secondary disease. DESIGN:
      Formalin-fixed, paraffin-embedded sections of 98 EMPD specimens from 61 patients
      (45 primary and 16 secondary) were immunostained with CK7, CK20, HER-2/neu, BRST
      2, CDX2, androgen receptor (AR), and cyclin D1. The study included 44 women and
      17 men (median age: 73 years). Median follow-up time was 47 months. RESULTS: All
      EMPD specimens were vibrantly positive for CK7. The frequency of positivity for
      all EMPD samples was CK20 (28%), BRST-2 (40%), HER-2/neu (64%), CDX2 (10%), AR
      (16%), and cyclin D1 (76%). For primary EMPD, the frequency of positivity was
      CK20 (22%), BRST-2 (48%), HER-2/neu (65%), CDX2 (2%), AR (21%), and cyclin D1
      (84%). For secondary EMPD, the frequency of positivity was CK20 (50%), BRST-2
      (25%), HER-2/neu (60%), CDX2 (33%), AR (0%), and cyclin D1 (53%). Notably, all 6
      of 7 cases of EMPD secondary to an anorectal adenocarcinoma tested were HER-2/neu
      negative and 5 of those 6 cases (80%) were CDX2 positive. CONCLUSIONS: The role
      of CK7, CK20, and BRST-2 in distinguishing primary and secondary EMPD is limited
      because CK20 and BRST-2 were positive in large subsets of both groups. An
      expanded immunohistochemical panel, including HER-2/neu and CDX2, may be useful
      in discriminating primary EMPD from EMPD secondary to anorectal adenocarcinoma
      but fails to distinguish primary EMPD from EMPD secondary to urothelial or
      prostatic malignancy. The consistent overexpression of HER-2/neu in primary EMPD
      suggests a role for trastuzumab therapy in patients with recurrent disease.

PMID- 20051816
TI  - Cutaneous metastases: a study of 78 biopsies from 69 patients.
AB  - A retrospective study of all cases of cutaneous metastases received in the
      Department of Pathology during the last 13 years was performed. Seventy-eight
      cases from 69 patients were examined. The majority of the patients were between
      60 and 80 years of age. The most frequent anatomical location for the metastases
      was the abdomen. Regarding the primary tumor, breast carcinoma was the most
      common. In females breast carcinoma was the most common, while lymphomas
      predominated in males. In 14 patients (17.95%), the origin of the primary tumor
      was unknown. In all these cases, there was no clinical suspicion of metastasis.
      Epidermotropism was found in only 9 out of 78 cases (11.54%). Contrary to this,
      vascular invasion was a common feature, being present in 49 out of 78 cases
      (62.82%). Necrosis was evident in 38 cases (48.72%), but it was either moderate
      or prominent only in 8 cases (10.26%). Inflammatory infiltrate was absent in 3
      cases (3.85%), mild in 49 (62.82%), moderate in 20 (25.64%), and prominent
      (graded either 3 of 4 or 4 out of 4) in 5 cases (6.41%). The metastases involved
      exclusively the dermis in 26 cases (33.33%), hypodermis in 7 cases (8.97%), and
      dermis and hypodermis in 44 cases (56.41%). We concluded that vascular invasion
      is a common feature in cutaneous metastases, especially in nonhematologic
      neoplasms, and because sometimes is focal, it should be carefully searched.

PMID- 20051817
TI  - The effects of Stichopus japonicus acid mucopolysaccharide on the apoptosis of
      the human hepatocellular carcinoma cell line HepG2.
AB  - In this study, the effects of Stichopus japonicus acid mucopolysaccharide (SJAMP)
      on the apoptosis of the human hepatocellular carcinoma cell line HepG2 were
      examined. The underlying mechanism was investigated by determining the effect of
      SJAMP on the expression of Bcl-2 and nm23-H1 genes in HepG2 cells. In vitro
      cultured HepG2 cells were treated with different concentrations of SJAMP. The
      dimethylthiazol (MTT) assay was used to determine the inhibition of cell
      proliferation. Expression of Bcl-2 and nm23-H1 genes was determined by Western
      blot analysis. The results showed that SJAMP inhibited the proliferation of HepG2
      cells in a time- and dose-dependent manner, SJAMP induced apoptosis in HepG2
      cells, and SJAMP decreased the expression of Bcl-2 and increased the expression
      of nm23-H1. We conclude that SJAMP inhibits the proliferation of HepG2 cells by
      inducing apoptosis. These results provide a theoretical basis for the utilization
      of SJAMP as a potential antitumor component for the treatment of hepatocellular
      carcinoma.

PMID- 20051818
TI  - Suprasellar germinoma masquerading as lymphocytic hypophysitis associated with
      central diabetes insipidus, delayed sexual development, and subsequent
      hypopituitarism.
AB  - We report the case of an 18-year-old woman with suprasellar germinoma
      masquerading as lymphocytic hypophysitis, which was associated with central
      diabetes insipidus, delayed sexual development, and hypopituitarism. Magnetic
      resonance imaging revealed an enlarged pituitary gland, thickened pituitary
      stalk, and a mass lesion in the inferior hypothalamus; these findings are typical
      of lymphocytic hypophysitis. Despite the administration of prednisolone therapy
      for 3 months, an enlarged irregular cystic mass lesion developed in the pituitary
      stalk and inferior hypothalamus. Open cranial surgery of the posterior pituitary
      revealed the presence of a germinoma. Therefore, chemotherapy and stereotactic
      radiation therapy were administered, resulting in complete remission of the
      germinoma. This case illustrates that the presence of an intrasellar mass lesion
      in association with pituitary stalk thickening can often cause difficulties in
      differential diagnosis. We believe that lymphocytic hypophysitis in pubertal
      children may be the first sign of a host reaction to an occult germinoma.

PMID- 20051819
TI  - A ruptured cerebral mycotic aneurysm caused by Abiotrophia defectiva
      endocarditis.
AB  - We describe a case of ruptured cerebral mycotic aneurysm caused by Abiotrophia
      defectiva endocarditis in a previously healthy man. The patient underwent
      craniotomy with clipping of aneurysm and received antibiotic treatment for 6
      weeks and survived.

PMID- 20051820
TI  - Change of heart.

PMID- 20051821
TI  - Delayed hemolytic transfusion reaction in sickle cell disease.
AB  - Delayed hemolytic transfusion reactions are potentially life-threatening
      complications observed in patients with sickle cell disease. We review the
      clinical features, pathophysiology, laboratory evaluation, and management of this
      complication. It is important that delayed hemolytic transfusion reactions be
      included in the differential diagnosis of acute pain episodes following a red
      blood cell transfusion in a patient with sickle cell disease.

PMID- 20051822
TI  - Adenosine stress magnetic resonance imaging in women with low risk chest pain:
      the Emory University experience.
AB  - OBJECTIVES: The purpose of this study was to evaluate the accuracy of adenosine
      stress magnetic resonance imaging (ASMRI) for the evaluation of women with low
      risk chest pain (CP). BACKGROUND: Coronary artery disease (CAD) can present
      differently among women than among men. There is increased interest in the use of
      ASMRI for lower risk patients in the emergency department to rule out CAD, and it
      would be valuable to assess its performance specifically in women. METHODS: This
      study included 82 women with low-risk CP who presented to the emergency
      department during a 2-year period at our institution and were evaluated by ASMRI.
      Clinical events were followed by review of medical records. RESULTS: The
      specificity of ASMRI for ischemia detection in this small cohort of patients was
      100%. Sensitivity was 94.9%, negative predictive value 100%, and positive
      predictive value 42.9%. CONCLUSIONS: ASMRI may be used as the initial imaging
      modality for ruling out CAD in women with low-risk CP because of its very high
      sensitivity, specificity, and negative predictive value for the detection of
      ischemia. Further randomized controlled trials comparing ASMRI with established
      noninvasive nuclear and echocardiographic stress modalities are needed.

PMID- 20051823
TI  - A 42-year-old man with fevers, chills and abdominal pain.

PMID- 20051824
TI  - Practice advisory for the prevention, diagnosis, and management of infectious
      complications associated with neuraxial techniques: a report by the American
      Society of Anesthesiologists Task Force on infectious complications associated
      with neuraxial techniques.

PMID- 20051825
TI  - Reduction in skin microvascular density and changes in vessel morphology in
      patients treated with sunitinib.
AB  - Hypertension is a common side effect in cancer patients treated with inhibitors
      of vascular endothelial growth factor/vascular endothelial growth factor receptor
      2 signaling and may represent a marker of clinical benefit. Functional
      rarefaction (a decrease in perfused microvessels) or structural rarefaction (a
      reduction in anatomic capillary density) may play an important role in the
      development of hypertension. We investigated whether sunitinib caused impairment
      of microvascular function and/or reduction of capillary density in patients with
      metastatic renal cell cancer (mRCC). Sixteen mRCC patients were treated with
      sunitinib (50 mg/day). Assessments of 24-h ambulatory blood pressure,
      microvascular endothelial function by laser Doppler fluxmetry, and capillary
      density by capillary microscopy were performed at baseline and days 14 and 28.
      Median blood pressure had increased on day 14 (systolic 10 mmHg, P<0.01 and
      diastolic blood pressure 8 mmHg, P<0.01). Capillary density had decreased from 69
      to 61 capillaries/mm (P<0.01). This decrease was related to the increase in
      systolic and diastolic blood pressure (r=-0.57, P<0.05 and r=-0.68, P<0.01,
      respectively). A more pronounced decrease in capillary density was associated
      with increased visibility of the subpapillary plexus (P=0.041). Preliminary
      findings indicated that median progression-free survival was significantly
      prolonged in patients with a greater than 6 capillaries/mm decrease in density as
      compared with patients with a less pronounced decrease (P=0.044). In conclusion,
      reduction in skin capillary density is associated with a rise in blood pressure
      during sunitinib therapy and, by itself, might be useful as a predictive marker
      of clinical outcome.

PMID- 20051826
TI  - The benzoylurea derivative F13 inhibits cell growth, migration and invasion
      through inducing expression of ERK1/2-mediated RECK in fibrosarcoma HT-1080
      cells.
AB  - 3-Bromoacetamino-4-methoxy-benzoylurea (F13) is a benzoylurea derivative selected
      from the library of small molecule tubulin ligands. Our earlier data showed that
      F13 had lost the capacity to interrupt microtubule dynamics while reserving
      anticancer activity. In this study, we found that F13 greatly inhibited cell
      proliferation in various human cancer cells. At concentrations of more than 1
      microg/ml, F13 markedly slowed growth and induced apoptosis in HT-1080 cells.
      This apoptosis occurred through cleavages of caspase 3 and PARP. At low
      concentrations (< or =1 microg/ml), F13 reduced the migration, adhesion, and
      invasion of HT-1080 cells. In addition, F13 downregulated the activities of
      matrix metalloproteinase-2/9 (MMP-2/9) in a culture supernatant. This was found
      to occur through the upregulation of the reversion-inducing cysteine-rich protein
      with Kazal motifs (RECK), a membrane-anchored inhibitor of MMPs, which acts by
      reducing ERK1/2 phosphorylation. Our data suggested that F13 might act as a novel
      RECK inducer, inhibiting cancerous processes with the inactivation of MMP-2/9 by
      the induction of RECK through the inhibition of ERK1/2 signalling transduction.

PMID- 20051827
TI  - Reversal of taxol resistance by cisplatin in nasopharyngeal carcinoma by
      upregulating thromspondin-1 expression.
AB  - Drug resistance often causes failure of chemotherapy in nasopharyngeal carcinoma
      (NPC). Thus, it is of great importance to overcome drug resistance by developing
      effective reversal therapies. The purposes of this study were to examine whether
      cisplatin could reverse the taxol-resistant phenotype of NPC cells, and to
      evaluate the role of the taxol-resistant gene (TXR1)/thrombospondin (TSP1)
      pathway in the reversal of taxol resistance. A drug (taxol)-resistant cell line,
      CNE-1/taxol, was established from a human NPC cell line, CNE-1. The sensitivity
      of both CNE-1 and CNE-1/taxol to cisplatin or paclitaxel was detected using the
      colony formation assay. Apoptotic death was measured by flow cytometry. The
      expression of the TXR1 and TSP1 was determined by RT-PCR and western blot. The
      growth inhibition rate in CNE-1/taxol cells in response to taxol was
      significantly increased when they were pre-treated with low-dose cisplatin. CNE
      1/taxol cells were more sensitive to cisplatin than CNE-1 cells when exposed to
      300-1500 nmol/l of cisplatin. An approximate seven-fold increase in TXR1 mRNA
      expression and an 8.9-fold decrease in TSP1 mRNA expression were observed in
      taxol-resistant cells compared with their parental cells. An 8.7-fold increase in
      TSP1 mRNA expression was observed in CNE-1/taxol cells exposed to 590 nmol/l of
      cisplatin for 24 h. An increase in TSP1 protein expression was obtained in a dose
      dependent manner after CNE-1/taxol cells were exposed to cisplatin. However,
      there was no change in TXR1 mRNA expression after both CNE-1 and CNE-1/taxol
      cells were exposed to cisplatin. We conclude that cisplatin reverses drug
      resistance through the upregulation of TSP1 downstream of TXR1.

PMID- 20051829
TI  - Hemodialysis access flow measurements using flow dilution and in-line dialysance
      are not interchangeable for hemodialysis access flow surveillance.

PMID- 20051830
TI  - Is lower limb venous drainage during peripheral extracorporeal membrane
      oxygenation necessary?
AB  - Extracorporeal membrane oxygenation (ECMO) is becoming a gold standard in acute
      heart failure, not responsive to inotrops and intra-aortic balloon
      contrapulsation. This diffusion is due to the possibility to implant it through
      peripheral cannulation and to perform long-time assistance. Nevertheless, this
      technique implies some problems concerning inferior limb perfusion. It is widely
      accepted that arterial distal cannulation and perfusion of the limb is mandatory,
      especially for long periods of assistance; but the necessity to implant a distal
      venous drainage is still discussed. We would like to present our experience on
      peripheral ECMO where we could avoid venous distal drainage uneventfully.

PMID- 20051831
TI  - In vivo evaluation of hydroxyapatite nanocoating on polyester artificial vascular
      grafts and possibility as soft-tissue compatible material.
AB  - The efficacy of hydroxyapatite (HAp) nanocoating on polyester vascular grafts was
      investigated in animal experiments. The HAp nanocrystals were covalently bonded
      separately between hydroxyl groups on a nanocrystal and alkoxysilyl groups in
      gamma-methacryloxypropyl triethoxysilane graft polymerized on a polyester
      substrate. Twelve HAp-coated polyester grafts and 10 control grafts of 20, 30, or
      50 mm in length were implanted in canine common carotid arteries. Serious
      complications or occlusions were not observed in any of the dogs after
      implantation. A histologic evaluation was conducted by staining with hematoxylin
      and eosin (HE), the von Willebrand factor (vWf), and alpha-smooth muscle actin
      (alpha-SMA) around the inner lumen of the grafts. The number of inflammation
      cells and giant cells in the HAp-coated group was significantly lower than that
      in the group receiving noncoated grafts (p < 0.05).

PMID- 20051832
TI  - Obesity and left ventricular assist device driveline exit site infection.
AB  - Driveline exit site (DLES) infection is a persistent problem among the left
      ventricular assist device (LVAD) patients. This study investigated the
      relationship between obesity and DLES infection. Records of LVAD patients at two
      institutions from January 1999 to January 2009 were queried. Results were
      analyzed using t tests. Those with LVAD support > or =90 days were included. The
      body mass index (BMI) of each patient was measured at the time of implant and at
      the conclusion of LVAD support or currently, if the patient was ongoing. Other
      data included preimplant age, ejection fraction, blood urea nitrogen, creatinine,
      diabetes, New York Heart Association class, pulmonary capillary wedge pressure,
      VO2 max, and inotrope therapy. The 118 patients who qualified for the study were
      placed in an infection group (n = 36) or in the control group (n = 82). Both
      groups had similar preimplant characteristics. Variables with differences
      statistically significant between the groups included duration of LVAD support,
      indication for support, device type, and BMI. Patients who developed DLES
      infections had a significantly higher BMI and continued weight gain over the
      course of LVAD therapy compared with the control group. Although this association
      requires further study, implications for clinical practice may include the
      provision of nutrition and exercise counseling for patients undergoing LVAD
      therapy, especially if overweight. These results may warrant increased measures
      to prevent and treat infection in the preimplant and postimplant periods.

PMID- 20051833
TI  - The influence of the residual stress in silicone tubes in the calibration methods
      of roller pumps used in cardiopulmonary bypass.
AB  - The rotation of rollers in cardiopulmonary bypass pumps propels the blood through
      various devices to reach the patient. Very occlusive settings may squeeze red
      blood cells, whereas a nonocclusive setting may result in retrograde flow.
      Occlusion of roller pumps may be regulated either by measuring the drop rate or
      by dynamic calibration. This study evaluated the influence of silicone tubing
      residual stress found on pump regulation. Silicone tubes obtained from two
      different suppliers were used in 6-inch DeBakey roller pumps. The variations
      occurring over time in the measurements of drop rate, dynamic calibration, and
      tube residual stress were analyzed. Covariance analysis of the four linear
      regressions has shown a progressive and accentuated reduction in drop rate (p <
      0.002). It is noticeable that the angular coefficients of the drop rate
      measurements of the four silicone tubes are the same (p > 0.56). This reduction
      in drop rate measurements may affect the regulation of the pumps before surgical
      procedures. One probable cause for this reduction is the residual stress found in
      the silicone tubes. Settings based on the dynamic calibration process tended to
      be repeated over time. Simple linear regression test (angular coefficient equals
      zero) has shown a p > 0.79 showing no interference of the silicone tubes residual
      stress on dynamic calibration, suggesting that one should use this method to
      calibrate roller pumps.

PMID- 20051834
TI  - The adjustable systemic-pulmonary artery shunt provides precise control of flow
      in vivo.
AB  - The ratio of pulmonary:systemic blood flow (Qp:Qs) remains problematic after
      single ventricle reconstruction. The adjustable systemic-pulmonary artery shunt
      (AS) was created as a solution for this problem. Prototype ASs were created using
      a screw-plunger mechanism as a variable resistor. A stepper motor controls
      plunger displacement. Six adult dogs underwent placement of a 4-mm AS in the
      femoral position to test its ability to control flow. Shunts were placed as
      arteriovenous fistulae to simulate the continuous flow of systemic-pulmonary AS.
      The 3.5-mm control shunts (CS) were placed on the contralateral side. The stepper
      motor was rotated from fully open to 3.4 mm of plunger depression for six
      complete cycles. Flow in the fully open AS was 687.9 +/- 28.7 cc/min* vs. 578.7
      +/- 26.8 cc/min in the CS (flow +/- standard error, *p < 0.005 vs. CS). Standard
      deviation of flow was similar between the AS and CS, implying hysteresis in
      resistor function did not contribute to flow variability. Peak torque requirement
      to turn the resistor was 2.4 mNm. The AS offers excellent control of flow in
      vivo. Control of Qp:Qs may lead to improved outcomes for single ventricle
      reconstructions.

PMID- 20051835
TI  - Expanded pediatric cardiovascular simulator for research and training.
AB  - A mock circulation system has been developed to approximate key anatomic features
      and simulate the pressures and flows of an infant. Pulsatile flow is generated by
      10 cc pulsatile ventricles (Utah infant ventricular assist device). Systemic
      vasculature is mimicked through the use of 3/8" ID bypass tubing with two
      flexible reservoirs to provide compliance. Vascular resistance, including
      pulmonary, aortic, and major branches, is controlled via a series of variable
      pinch clamps. The coronary branch has a dynamic resistor so that the majority of
      flow occurs during diastole. The system is instrumented to measure key pressures
      and flows. Right atrial pressure, left atrial pressure, pulmonary artery
      pressure, and mean aortic pressure are measured with high-fidelity pressure
      catheters (Millar Instruments, Houston, TX). Flows are measured by transit time
      ultrasonic flow probes (Transonic Systems, Ithaca, NY) in the pulmonary artery,
      aorta, coronary artery, and brachiocephalic artery along with assist device flow.
      The system can be tuned to create the hemodynamic values of a pediatric patient
      under normal or heart failure conditions. Once tuned to the desired hemodynamic
      conditions, the loop may be used to test the performance of various circulatory
      support systems including the intra-aortic balloon pump, left and right
      ventricular assist devices, or cardiopulmonary support systems such as
      extracorporeal membrane oxygenation.

PMID- 20051836
TI  - Comparison between standard heparin and tinzaparin for haemodialysis catheter
      lock.
AB  - Tinzaparin offers some advantages over unfractionated heparin (UFH) for
      hemodialysis circuit anticoagulation. No study has compared these two molecules
      as hemodialysis catheter locks. This study aimed to compare the efficacy of
      tinzaparin and UFH as locks for hemodialysis tunnelled central venous catheter in
      patients with end-stage renal disease (ESRD). A randomized, prospective, single
      blinded, controlled study was undertaken. Patients were randomly assigned to
      receive UFH and tinzaparin for two 7-week periods in a crossover fashion. The
      doses used were 5,000 U of UFH and 2,000 U of tinzaparin per catheter line. The
      primary outcome was the need for thrombolytic catheter lock use defined with the
      Hemodialysis Unit alteplase protocol. Forty-two patients with ESRD were enrolled,
      totalling 815 UFH lock sessions and 729 tinzaparin lock sessions. A 47.4%
      reduction in the incidence of alteplase lock use was observed with tinzaparin
      lock (3.16% vs. 6.01%, chi-square, p = 0.0078). There was no significant
      difference in the time to first alteplase use between the two locks by Kaplan
      Meier survival analysis (logrank, p = 0.0900). Our results suggest that
      tinzaparin could be an appropriate alternative for a hemodialysis tunnelled
      central venous catheter lock, but these results should be confirmed with a larger
      trial.

PMID- 20051837
TI  - Hydraulic testing of intravascular axial flow blood pump designs with a
      protective cage of filaments for mechanical cavopulmonary assist.
AB  - To provide hemodynamic support to patients with a failing single ventricle, we
      are developing a percutaneously inserted, magnetically levitated axial flow blood
      pump designed to augment pressure in the cavopulmonary circulation. The device is
      designed to serve as a bridge-to-transplant, bridge-to-recovery, bridge-to
      hemodynamic stability, or bridge-to-surgical reconstruction. This study evaluated
      the hydraulic performance of three blood pump prototypes (a four-bladed impeller,
      a three-bladed impeller, and a three-bladed impeller with a four-bladed diffuser)
      whose designs evolved from previous design optimization phases. Each prototype
      included the same geometric protective cage of filaments, which stabilize the
      rotor within the housing and protect the housing wall from the rotating blades.
      All prototypes delivered pressure rises over a range of flow rates and rotational
      speeds that would be sufficient to augment hemodynamic conditions in the
      cavopulmonary circulation. The four-bladed impeller outperformed the two
      remaining prototypes by >40%; this design was able to generate a pressure rise of
      4-28 mm Hg for flow rates of 0.5-10 L/min at rotational speeds of 4,000-7,000
      RPM. Successful development of this blood pump will provide clinicians with a
      feasible therapeutic option for mechanically supporting the failing Fontan.

PMID- 20051838
TI  - Elevated B-type natriuretic peptide without volume overload in a left ventricular
      assist device patient with a subdural hematoma.
AB  - We report a case of elevated B-type natriuretic peptide (BNP) without volume
      overload in a left ventricular assist device patient with a subdural hematoma and
      cerebral salt wasting syndrome suggesting a noncardiac etiology for BNP
      elevation.

PMID- 20051839
TI  - LIFEBRIDGE B2T--a new portable cardiopulmonary bypass system.
AB  - The LIFEBRIDGE B2T is a new portable cardiopulmonary bypass (CPB) system designed
      for temporary circulatory support. The LIFEBRIDGE B2T consists of a disposable
      patient unit with a CPB circuit, a control, and a base unit. The system weighs 20
      kg. We used the LIFEBRIDGE B2T in four patients for circulatory support in
      beating heart coronary artery bypass graft for complete revascularization. The
      LIFEBRIDGE B2T was connected via femoral cannulation. Concentrations of free
      hemoglobin (fHb), interleukin (IL)-6, and -8 were measured. For venous blood
      drainage, 22-24 Fr cannulae and for arterial cannulation, 16-20 Fr cannulae were
      used. Average extracorporeal circulation (ECC) time was 61 +/- 18 minutes. During
      circulatory support, the system delivered an arterial blood flow between 3.1 and
      4.1 L/min. The negative pressure at the venous drainage was between -79 and -45
      mm Hg. During circulatory support, fHb concentration increased from 5.8 +/- 1.7
      mg/dL to a maximum of 10.2 +/- 6.2 mg/dL. Also, IL-6 and -8 increased from 2.1 +/
      0.06 to 503.3 +/- 400.7 U/L and 5.9 +/- 0.9 to 66.5 +/- 46.8 U/L, respectively.
      The LIFEBRIDGE B2T is a new portable and safe circulatory support system.
      Connected via femoral cannulation, the system provides adequate arterial blood
      flow and an acceptable negative pressure at the venous cannula. The fHb
      concentration showed only a moderate increase during ECC.

PMID- 20051840
TI  - Is systemic inflammation of hemodialysis patients improved with the use of
      enalapril? Results of a randomized, double-blinded, placebo-controlled clinical
      trial.
AB  - This study compared the effect of enalapril versus placebo on serum tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and C-reactive protein (CRP) in
      hemodialysis in a randomized, double- blinded, controlled clinical trial.
      Patients without infection or antiinflammatory drugs were randomly allocated to a
      study (n = 13, enalapril, 20 mg/day) or control (n = 12, placebo) group; all had
      arteriovenous fistula. Serum TNF-alpha, IL-6, and CRP were measured at 0, 1, and
      3 months. Systolic blood pressure (baseline vs. final) was 151 +/- 25 vs. 135 +/-
      19 mm Hg (p < 0.05) in the study group and 154 +/- 21 vs. 144 +/- 27 mm Hg in
      control group; diastolic blood pressure was 86 +/- 9 vs. 76 +/- 13 and 91 +/- 16
      vs. 81 +/- 18 mm Hg, respectively; median (percentiles 25%-75%) IL-6 (baseline
      vs. final) was 4.2 (3-8) vs. 4.1 (2-9) pg/mL and 6.3 (3-9) vs. 6.7 (3-8) pg/mL;
      and CRP was 1.9 (1-7) vs. 3.0 (1-12) mg/L and 4.7 (1-16) vs. 3.9 (2-16) mg/L,
      respectively. TNF-alpha was detected in only two patients. Enalapril
      significantly reduced blood pressure in hemodialysis patients, but it did not
      decrease IL-6 and CRP compared with placebo.

PMID- 20051841
TI  - Identification and functional characterization of a novel nonsense mutation in
      FGA accounting for congenital afibrinogenemia in six Egyptian patients.
AB  - Congenital afibrinogenemia is a rare coagulation disorder attributed to over
      forty mutations found either in homozygosity or in compound heterozygosity, the
      majority localized in FGA encoding the fibrinogen Aalpha-chain. Despite the
      number of genetic analyses performed the study of additional patients still
      allows the identification of novel mutations and a better understanding of
      fibrinogen structure and function. Here we report the identification and
      functional analysis of a novel nonsense mutation in FGA exon 5: c.718C>T
      (CAG>TAG) p.Q240X (Q221X in the mature chain lacking the signal peptide),
      accounting for fibrinogen deficiency in six Egyptian patients. Expression of the
      mutant Aalpha-chain cDNA in combination with wild-type Bbeta-chain and gamma
      chain cDNAs demonstrated that although the mutant chain could be detected in the
      cell media of transfected COS-7 cells it was less secreted in comparison to the
      wild-type Aalpha-chain. Our patients were all homozygous for p.Q240X(Q221X) yet
      their clinical spectrum varied considerably in their onset of presentation or
      severity, with bleeding ranging from moderate mucous membrane bleeds in
      adolescence to life threatening intracranial hemorrhage in infancy.

PMID- 20051842
TI  - A laboratory evaluation into the short activated partial thromboplastin time.
AB  - Although short activated partial thromboplastin times (APTTs) are generally
      considered to be laboratory artefacts of problematic blood collections, there is
      mounting evidence that in some cases a short APTT may reflect a hypercoagulable
      state, potentially associated with increased thrombotic risk and adverse
      cardiovascular events. We prospectively evaluated the phenomenon of short APTTs
      in 113 consecutive samples compared with an equal number of age and sex-matched
      normal APTT samples. We found a significant difference in various test parameters
      including prothrombin time (PT), Factor (F) V, FVIII, FXI, FXII, von Willebrand
      factor (VWF) antigen and collagen-binding activity, and in the level of
      procoagulant phospholipids, as assessed using a novel assay procedure (XACT).
      Interestingly, there was a significant negative association for fibrinogen, and
      although elevated, there was no significant association for FIX. On the basis of
      identified consecutive samples having multiple low APTTs on several sequential
      days, a proportion of laboratory-defined short APTTs appear to represent in-vivo
      hypercoagulability. In conclusion, plasma from patients presenting with short
      APTTs is reflective of a complex hypercoagulant milieu that could feasibly
      contribute to thrombotic risk, and 20% or more of laboratory definable short
      APTTs appear to reflect in-vivo phenomenon.

PMID- 20051843
TI  - The effect of four hemostatic gene polymorphisms on the outcome of septic
      critically ill patients.
AB  - Genetic variants of hemostatic factors leading to prothrombotic phenotypes of
      hypercoagulability and hypofibrinolysis might affect prognosis of septic
      critically ill patients. Our aim was to evaluate the effect of four hemostatic
      genetic variants, namely fibrinogen-beta-455G/A, factor XIII (FXIII) V34L,
      plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphisms and factor V Leiden
      (FVL) mutation on survival of critically ill patients with severe sepsis or
      septic shock. A prospective, observational study in an 18-bed general ICU
      included 73 patients with severe sepsis or septic shock. Epidemiological,
      laboratory data and comorbidities along with severity scores were recorded.
      Genotyping for fibrinogen-beta-455G/A, FXIII V34L and PAI-1 4G/5G polymorphism
      and FVL mutation was carried out in all patients. The primary outcomes were the
      28-day and the 90-day survival. Age, septic shock, severity indexes, prior
      steroid use and arterial pH were identified as predictors of the 28-day and 90
      day survival in both the univariate and the multivariate models. On the contrary,
      none of the examined polymorphisms was found to significantly affect either the
      28-day or the 90-day survival. Our data suggest that the importance of these
      hemostatic polymorphisms as predictors of the prognosis of sepsis in critically
      ill patients is probably very small.

PMID- 20051844
TI  - Hypocoagulability, as evaluated by thrombelastography, at admission to the ICU is
      associated with increased 30-day mortality.
AB  - Thrombelastography (TEG), a cell-based whole blood assay, may better reflect
      haemostatic competence than conventional coagulation assays and this was
      therefore evaluated including the clot forming parameters: R, angle and maximal
      amplitude in patients at ICU admission. This was a prospective, observational
      study of patients admitted to a general ICU at a tertiary care university
      hospital with an expected stay of more than 24 h. Blood samples for TEG and
      standard coagulation analysis were obtained at admission. The APACHE II and
      sequential organ failure assessment (SOFA) scores and 30-day mortality were
      recorded. At ICU admission, 106 patients (42%) showed hypocoagulability as
      evaluated by TEG and these patients had higher first day SOFA score (P < 0.0001)
      and higher 30-days (42 vs. 13%, P < 0.0001) mortality than patients presenting
      with a normal TEG. In 30-day survivors, admission platelet count (P = 0.05),
      angle (P < 0.001) and maximal amplitude (P = 0.001) were higher and R decreased
      (P = 0.0013) compared with nonsurvivors. Hypocoagulability at admission as
      evaluated by TEG was an independent risk factor for 30-day mortality [adjusted
      odds ratio (OR) 3.5; 95% confidence interval (CI) 1.7-7.1]. Hypocoagulability as
      evaluated by TEG was frequent at admission in general ICU patients and associated
      with a higher rate of ventilator treatment, higher rate of renal replacement
      therapy and a higher use of blood products. Hypocoagulability is an independent
      risk factor for 30-day mortality.

PMID- 20051845
TI  - Gene-environment interactions in asthma and allergy: the end of the beginning?
AB  - PURPOSE OF REVIEW: The pathogenesis of asthma and allergy typically involves not
      only distinct genetic and environmental factors, but also interactions between
      the two. Innate-immunity genes [particularly CD14, toll-like receptor (TLR)4 and
      TLR2, the critical mediators of responses to bacteria in the extracellular space]
      play a prominent role in gene-environment interactions relevant to asthma-related
      phenotypes because the interaction between microbial load and the innate-immune
      system is a critical determinant of both immune function and allergy/asthma
      susceptibility. This review presents recent findings illustrating the role of
      gene-environment interactions in asthma/allergy susceptibility. RECENT FINDINGS:
      Population studies have extended our understanding of the role of CD14 and innate
      immune genes in the interplay between genetic variants and the environment,
      highlighting the complexity of these interactions and their significant influence
      on susceptibility to asthma and allergy. SUMMARY: Gene-environment interactions
      have become a leitmotiv in asthma and allergy genetics, especially over the last
      3 years. The next challenge awaiting asthma and allergy geneticists will be to
      define the extent to which the search for gene-environment interactions can be
      successfully integrated with hypothesis-generating, genome-wide approaches aimed
      at the identification of genetic variants involved in the pathogenesis of complex
      lung diseases.

PMID- 20051846
TI  - An update on Legionella.
AB  - PURPOSE OF REVIEW: Legionella pneumophila is increasingly recognized as a
      significant cause of sporadic and epidemic community-acquired and nosocomial
      acquired pneumonia. This review focuses on the latest literature concerning the
      epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of
      Legionnaires' disease. RECENT FINDINGS: A significant increase in the incidence
      of Legionnaires' disease in the United States has been documented over the last
      years. L. pneumophila has recently been found to be a leading cause of community
      acquired pneumonia in hospitalized and ambulatory patients in Germany. Recent
      studies provide insight into the understanding of the pathogenesis of
      Legionnaires' disease and the relevance of the formation of biofilms. Clinical
      manifestations of Legionnaires' disease are not specific and current diagnostic
      scores are of limited use. Several recent studies offer useful information
      concerning Legionnaires' disease in immunosuppressed patients. A systematic
      review of English literature performed to assess test characteristics of
      Legionella urinary antigen has found that the pooled sensitivity of the test was
      0.74 and specificity was 0.991. Improved clinical response has been observed for
      patients with Legionnaires' disease treated with highly active antimicrobial
      agents against Legionella. SUMMARY: Legionnaires' disease is a significant health
      problem in many countries. Clinical manifestations are unreliable in diagnosing
      Legionnaires' disease. Therefore, diagnostic laboratory tests for Legionella,
      including the urinary antigen test, should be applied to all patients with
      pneumonia. Levofloxacin (or other fluoroquinolone) or azithromycin are the
      current drugs of choice for treatment of Legionnaires' disease. Effective
      preventive strategies are needed.

PMID- 20051848
TI  - Receptor and nonreceptor tyrosine kinases in vascular biology of hypertension.
AB  - PURPOSE OF REVIEW: Extensive evidence indicates that receptor tyrosine kinases
      and nonreceptor tyrosine kinases underlie vascular damage in hypertension.
      However, recent clinical studies using vascular endothelial growth factor (VEGF)
      receptor inhibitors (bevacizumab, axitinib) revealed the unexpected finding of
      increased blood pressure. Whether this is a generalized receptor tyrosine kinase
      phenomenon or a VEGF receptor-specific effect is unclear. The present review
      focuses on current findings regarding the role of tyrosine kinases and signaling
      in vascular pathobiology of hypertension. RECENT FINDINGS: Multiple complex and
      interacting signaling pathways activated by receptor and nonreceptor tyrosine
      kinases are upregulated and have been implicated in vascular alterations
      associated with high blood pressure. Experimental evidence suggests that receptor
      tyrosine kinase activation by direct ligand binding as well as by ligand
      independent mechanisms through transactivation by G protein-coupled receptors
      plays a role in vascular signaling and cardiovascular diseases. SUMMARY: Cellular
      mechanisms and signaling pathways mediated by tyrosine kinases involved in
      hypertensive vascular damage are currently the subject of intensive
      investigation. The unexpected finding of hypertension as a side effect in
      patients treated with VEGF receptor inhibitors suggests that some tyrosine
      kinases negatively regulate vascular function. Further characterization of these
      processes will provide greater understanding of the role of tyrosine kinases in
      vascular pathobiology in hypertension and should provide new insights on novel
      therapeutic targets.

PMID- 20051849
TI  - Dual blockade of the renin-angiotensin-aldosterone system in cardiac and renal
      disease.
AB  - PURPOSE OF REVIEW: Renin-angiotensin-aldosterone system (RAAS) blockade improves
      outcome in cardiovascular disease (CVD) and chronic kidney disease (CKD), but the
      residual risk during monotherapy RAAS blockade remains very high. This review
      discusses the place of dual RAAS blockade in improving these outcomes. RECENT
      FINDINGS: The combination of angiotensin-converting enzyme inhibitor (ACEI) with
      angiotensin II type 1 receptor blocker (ARB) generally had a better
      antihypertensive and antiproteinuric effect than monotherapy in many studies, but
      is also associated with more adverse effects. Unfortunately, the effect on hard
      renal and cardiovascular endpoints is not unequivocal. The combination of ACEI
      (or ARB) with aldosterone blockade has long-term benefits in heart failure, and
      an added effect on proteinuria in CKD, but data on hard renal endpoints are
      lacking. Dual blockade including renin inhibition has added antiproteinuric
      effects, but studies to gather long-term data are still under way. Available
      strategies to optimize the effect of monotherapy RAAS blockade include dose
      titration and correction of volume excess. Whether dual blockade has better
      efficacy and/or fewer adverse effects than optimized monotherapy has not been
      investigated. SUMMARY: Several options are available to increase the effect of
      monotherapy RAAS blockade. For proteinuric CKD, these can be combined in a
      stepwise approach aimed at maximal proteinuria reduction; this includes dual
      blockade for patients with persistent proteinuria during optimized monotherapy
      RAAS blockade. Long-term randomized studies, however, are needed to support the
      benefits of dual blockade for long-term renal and cardiovascular outcome in CKD.

PMID- 20051847
TI  - Defining and predicting severe community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: Community-acquired pneumonia is a significant clinical and
      public health problem. Defining and predicting severe pneumonia is difficult but
      important. RECENT FINDINGS: Several new predictive models and more sophisticated
      approaches to describing pneumonia severity have been recently proposed, with
      subsequent validation in varied patient populations. Early data suggest that
      biomarkers may be useful in the future. SUMMARY: Definitions of pneumonia
      severity depend on the relevant clinical or public health question. A health
      services reference definition seems most useful in most settings. The Infectious
      Disease Society of America/American Thoracic Society 2007 guidelines and SMART
      COP are two recent promising methods for predicting severe pneumonia at the time
      of presentation. The traditional pneumonia severity index and Confusion Uremia
      Respiratory rate Blood pressure (CURB)-65 models are less useful. Accurate
      assessment of severity has important implications for triage, outcome, and
      defining populations for research applications. Novel biomarkers, while somewhat
      promising, do not yet have a validated role in pneumonia severity assessment.

PMID- 20051850
TI  - Health-related quality of life outcomes in chronic kidney disease.
AB  - PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) endure compromised
      health-related quality of life (HRQOL). Although the link between HRQOL and
      increased mortality in patients with end-stage renal disease (ESRD) is well
      documented, less is known about the relationship between CKD and HRQOL. This
      article reviews the recent evidence on HRQOL, its correlates and proposed
      intervention strategies to improve HRQOL in CKD. RECENT FINDINGS: A growing body
      of literature indicates that various comorbid conditions related to CKD play a
      substantial role in impaired HRQOL in CKD. Hypertension, both a cause and
      complication of CKD, negatively affects HRQOL due to associated comorbidities,
      side effects from antihypertensive medications and awareness of the diagnosis.
      Anemia has been associated with HRQOL, but concerns about the safety of
      erythropoietin-stimulating agents (ESAs) have led to more conservative anemia
      treatment. Frailty, symptom burden and depression are also major contributory
      factors to HRQOL in CKD. SUMMARY: Certain determinants of HRQOL in CKD, namely
      anemia and depression, are treatable. Early identification and correction may
      improve overall well being of patients. Clinical trials are required to
      demonstrate whether treatment interventions benefit HRQOL in this high-risk
      population. Furthermore, whether integration of HRQOL assessment into routine
      clinical practice will improve HRQOL outcomes remains to be determined.

PMID- 20051851
TI  - Endothelin, hypertension and chronic kidney disease: new insights.
AB  - PURPOSE OF REVIEW: Endothelin is important in the development of cardiorenal
      disease. This review discusses recent developments in understanding endothelin's
      role in hypertension and chronic kidney disease (CKD). RECENT FINDINGS:
      Endothelin-1 production is increased in hypertension and CKD. Endothelin-1
      stimulates vasoconstriction, inflammation and fibrosis, thereby promoting
      hypertension, atherosclerosis and CKD. These effects are closely linked to
      angiotensin II and reactive oxygen species. In preclinical studies, endothelin
      receptor antagonists were effective in treating hypertension (particularly with
      endothelial dysfunction) and CKD. In preclinical studies, endothelin A-selective,
      as opposed to combined endothelin A and B, receptor blockers have generally been
      more efficacious. Few clinical trials have been conducted in hypertension and/or
      kidney disease, partly due to concerns over side effects of testicular toxicity
      and fluid retention. Endothelin blockade reduces blood pressure in patients with
      resistant hypertension, with additional beneficial metabolic effects. Endothelin
      antagonism improves proteinuria in CKD (diabetic or not), particularly in
      patients taking inhibitors of angiotensin II action. SUMMARY: Endothelin is a
      promising target in the treatment of resistant hypertension and CKD, with
      additional potential benefits on atherosclerosis and the metabolic syndrome. The
      nature and mechanisms of drug side effects require elucidation before the
      potential of this new class of drugs can be fully realized.

PMID- 20051852
TI  - Adipokines and blood pressure control.
AB  - PURPOSE OF REVIEW: In contrast to previous understanding, adipocytes are now
      known to produce an array of factors collectively termed 'adipokines', several of
      which have effects on the cardiovascular system. The marked rise in prevalence of
      obesity warrants investigation into the role of adipocyte-derived factors in the
      regulation of blood pressure. For example, dysregulated production of specific
      adipokines in the setting of obesity may contribute to hypertension commonly
      experienced in obese patients. This editorial highlights current concepts for
      regulation of adipokine production by adipocytes and their potential role in
      blood pressure regulation. RECENT FINDINGS: Adipocytes synthesize and release
      several factors that have been linked to blood pressure control, including
      adiponectin, leptin, angiotensin, perivascular relaxation factors and resistin.
      Increasing evidence suggests that aberrant production and release of these
      factors from adipocytes may contribute to the high prevalence of hypertension in
      the obese population. However, additional studies are warranted to define precise
      mechanisms for blood pressure regulation by these factors, and to delineate their
      role in obesity-related hypertension. SUMMARY: Studies aimed at determining the
      role of adipocyte-derived factors in blood pressure regulation during normal
      physiology and in the setting of obesity are needed.

PMID- 20051854
TI  - Microparticles, vascular function and hypertension.
AB  - PURPOSE OF REVIEW: To summarize the potential role of microparticles in
      hypertension and in cardiovascular diseases. Microparticles are submicron
      vesicles shed from the membrane in response to cell activation or apoptosis.
      Microparticles of different cellular origins are found in the plasma of healthy
      individuals and their circulating levels augment in patients with cardiovascular
      diseases. RECENT FINDINGS: Recent studies demonstrate that circulating levels of
      microparticles originating from endothelial cells, which represent a small
      fraction of the overall pool of plasma microparticles, augment with increased
      endothelial dysfunction in patients with cardiovascular diseases. Therefore,
      endothelial microparticles constitute an emerging surrogate marker of endothelial
      dysfunction, with potential prognostic value for major adverse events in patients
      with cardiovascular diseases. In addition, microparticles of endothelial and
      other cellular origins are also potential biological effectors in inflammation,
      vascular injury, angiogenesis and thrombosis. SUMMARY: In summary, circulating
      endothelial microparticles may serve not only as an index of arterial damage but
      also as a trigger of vascular repair.

PMID- 20051853
TI  - Essential hypertension and risk of nephropathy: a reappraisal.
AB  - PURPOSE OF REVIEW: Treating mild-to-moderate essential hypertension in
      nondiabetic African Americans fails to halt nephropathy progression, whereas
      hypertension control slows nephropathy progression in European Americans. The
      pathogenesis of these disparate renal syndromes is reviewed. RECENT FINDINGS: The
      nonmuscle myosin heavy chain 9 gene (MYH9) is associated with a spectrum of
      kidney diseases in African Americans, including idiopathic focal global
      glomerulosclerosis historically attributed to hypertension, idiopathic focal
      segmental glomerulosclerosis, and the collapsing variant of focal segmental
      glomerulosclerosis [HIV-associated nephropathy (HIVAN)]. Risk variants in MYH9
      likely contribute to the failure of hypertension control to slow progressive
      kidney disease in nondiabetic African Americans. SUMMARY: Early and intensive
      hypertension control fails to halt progression of 'hypertensive nephropathy' in
      African Americans. Genetic analyses in patients with essential hypertension and
      nephropathy attributed to hypertension, focal segmental glomerulosclerosis and
      HIVAN reveal that MYH9 gene polymorphisms are associated with a spectrum of
      kidney diseases in this ethnic group. Mild to moderate hypertension may cause
      nephropathy in European Americans with intrarenal vascular disease improved by
      the treatment of hypertension, hyperlipidemia and smoking cessation.

PMID- 20051855
TI  - Management of coexisting cataract and glaucoma.
AB  - PURPOSE OF REVIEW: The optimal management of cataract in the glaucoma patient
      must be constantly updated as advances in both subspecialties impact the surgical
      decision. RECENT FINDINGS: The primary considerations at this time include
      combining the procedures as opposed to sequential operations and optimizing the
      effectiveness of the operations while reducing complications. SUMMARY: Recent
      findings would certainly suggest an individualized approach based not only on the
      glaucoma and cataract condition of the patient but also on the experience of the
      surgeon with varied techniques. Further time and research are required to
      determine whether certain approaches or techniques will become more universally
      adopted. At present, there certainly is support for a variety of approaches.

PMID- 20051856
TI  - Cyclodialysis cleft: causes and repair.
AB  - PURPOSE OF REVIEW: To report the most recent developments in the diagnosis and
      management of cyclodialysis clefts. RECENT FINDINGS: Cyclodialysis clefts are
      rare. The most common reason for presentation is blunt-ocular trauma followed by
      various iatrogenic interventions. Diagnosis is particularly challenging and
      various new noninvasive techniques have been described to facilitate this
      process, such as ultrasound biomicroscopy (UBM) and the anterior segment OCT (AS
      OCT). The management of cyclodialysis clefts should be conservative initially
      followed by a variety of nonsurgical and surgical modalities to achieve closure.
      SUMMARY: The management of cyclodialysis clefts requires a step-wise approach.
      Initially, it is of particular importance to identify the full extent and
      location of the cleft as in some cases more than one cleft may be present
      requiring a variety of nonsurgical and surgical interventions. Nonincisional
      interventions include the application of various lasers and cryotherapy in the
      vicinity of the cleft. The traditional approach of direct cyclopexy has more
      recently been complemented by recent reports of employing modified external
      plombage procedures, vitrectomy and gas assisted endotamponade. There are
      insufficient studies formally evaluating these techniques to be able to assess
      their safety and efficacy.

PMID- 20051857
TI  - Gender and glaucoma: what we know and what we need to know.
AB  - PURPOSE OF REVIEW: With growing aging populations and an increase in cases of
      glaucoma and glaucoma blindness worldwide, aging populations are particularly at
      higher risk of glaucoma and glaucoma blindness. Awareness of the gender
      differences might increase attention toward populations at risk. RECENT FINDINGS:
      Women not only outlive men, but also outnumber men in glaucoma cases worldwide.
      Women are at higher risks for angle closure glaucoma, but there is no clear
      gender predilection for open angle glaucoma. Of interest, there is some evidence
      suggesting that female sex hormones might be protective of the optic nerve. In
      addition, it is hypothesized that decreased estrogen exposure is associated with
      increased risk for open angle glaucoma, yet population-based studies present
      inconsistent results. Presently, there is insufficient evidence to support
      hormonal replacement therapy use in glaucoma prevention. In addition, it appears
      that women carry a larger burden of glaucoma blindness due to longevity and
      disadvantages in socioeconomic/health beliefs. SUMMARY: Current evidence suggests
      that older women are at risk for glaucoma and glaucoma blindness. Further
      interdisciplinary research involving investigators, specialized in glaucoma,
      women's health and health disparities, will lead to better understanding of
      gender health disparities in glaucoma and better targeting populations at risk.

PMID- 20051858
TI  - The relevance of reward pathways for schizophrenia.
AB  - PURPOSE OF REVIEW: There has been a resurgence of interest in the field of reward
      processing in schizophrenia in recent years, aided by insights from functional
      neuroimaging. We examine how disturbances in reward-related processes relate to
      the pathophysiology and symptomatology of this disorder. RECENT FINDINGS:
      Behavioural and functional neuroimaging studies in psychosis demonstrate
      impairments in the representation of reward value and in reward-related learning
      and a failure to motivate behaviour for incentives. These impairments are linked
      to abnormal mesocorticolimbic and mesostriatal function. SUMMARY: Abnormalities
      in reward processing offer insights into the symptomatology of schizophrenia and
      its underlying neurobiology. Further investigation is required into the
      specificity of these deficits to particular symptom expression and to what extent
      they are improved by antipsychotic treatment.

PMID- 20051859
TI  - Olfactory function and schizophrenia: an update.
AB  - PURPOSE OF REVIEW: Olfaction is a field of growing interest in schizophrenia
      research. This article reviews recent studies on olfactory functions in
      schizophrenia. RECENT FINDINGS: The current literature provides additional
      insights into olfactory deficits, abnormalities, and olfactory hedonic
      dysfunction in schizophrenia. Recent findings reinforce particular associations
      with negative symptoms and deficit syndrome schizophrenia. Studies indicate that
      abnormalities in patients with schizophrenia extend to more peripheral olfactory
      structures and functions, including olfactory receptor neuron dysfunction.
      Olfactory identification ability was found to relate to prodromal disorganization
      symptoms in young high-risk patients. Further support for the notion of a genetic
      contribution to olfactory dysfunction in schizophrenia derives from studies
      reporting physiological olfactory dysfunction (olfactory event-related
      potentials) in unaffected relatives, and an odor-specific hyposmia, present in
      both patients with schizophrenia and family members. SUMMARY: Further research is
      needed to improve our understanding of olfactory dysfunction in schizophrenia.
      Recent encouraging findings underscore that the olfactory system is a field of
      research that holds promise for advancing our understanding of the
      pathophysiology of schizophrenia and possibly as a useful endophenotypic marker
      of neurodevelopmental vulnerability.

PMID- 20051860
TI  - Why do patients with schizophrenia smoke?
AB  - PURPOSE OF REVIEW: Among the mentally ill, smoking prevalence is highest in
      patients with schizophrenia ( approximately 70-80%). This can impose a
      significant financial burden on patients, not to speak of increased smoking
      related morbidity and mortality. Therefore, it is critical for clinicians to
      understand why patients with schizophrenia smoke in order to adapt treatment
      schemes. Understanding the reasons may also help to develop new drugs that target
      the nicotinic system in the brain as well as smoking cessation programs that are
      specifically designed for this particular patient population. RECENT FINDINGS: So
      far, several reasons have been identified which are believed to explain tobacco
      consumption in patients with schizophrenia. Originally, it was widely believed
      that patients with schizophrenia smoke to increase hepatic clearance and to
      restore the dopamine blockade of certain antipsychotic drugs to diminish their
      side effects. However, more recently it became obvious that cigarette smoking may
      also be reinforcing for patients because it improves psychiatric symptoms, most
      notably negative and cognitive symptoms. The underlying molecular mechanisms of
      these nicotine effects are currently under intensive investigation. SUMMARY:
      Heavy smoking in schizophrenia cannot simply be viewed as a 'bad habit'. Rather,
      self-medication of clinical symptoms and side effects of antipsychotic drugs
      appear to play a major role.

PMID- 20051861
TI  - Polypharmacy in schizophrenia.
AB  - PURPOSE OF REVIEW: Although most guidelines recommend monotherapy in
      schizophrenia, the combined application of multiple psychotropic agents is very
      common, especially in treatment-refractory cases. We review the empirical basis
      supporting these attempts and their relevance for clinical practice. RECENT
      FINDINGS: Polypharmacy intends to address different aspects of treatment
      resistance, most importantly insufficient response of psychotic positive and
      negative symptoms, but also cognitive disturbances, affective comorbidity,
      obsessive-compulsive syndromes and side-effects of antipsychotic drugs. This
      review summarizes the current state of evidence of combined antipsychotic
      treatment strategies and the augmentation of antipsychotics with mood
      stabilizers, antidepressants and experimental substances. SUMMARY: In general,
      rigorous data on combination therapy in schizophrenia are rare and further
      randomized controlled trials, naturalistic trials and head-to-head-trials are
      necessary. Some evidence supports a combination of antipsychotics and
      antidepressants for negative symptoms and comorbid major depressive episodes. The
      add-on of lithium and mood stabilizers lacks compelling evidence, but might be
      beneficial for specific subgroups. For treatment-resistant cognitive symptoms,
      antipsychotic medication should be combined with cognitive remediation, as no
      pharmacological add-on strategy has gained convincing evidence so far. Treatment
      emergent positive and/or negative symptoms under clozapine monotherapy might
      benefit from adding a second atypical substance.

PMID- 20051862
TI  - Genetics of vasculitis.
AB  - PURPOSE OF REVIEW: Evidence for a genetic contribution to risk for developing
      different forms of vasculitis has accumulated recently. Cohorts have been
      assembled that are of sufficient size to allow application of up-to-date methods
      of genetic analysis. This review will summarize the current understanding of the
      genetics of several forms of vasculitis. RECENT FINDINGS: The first genome-wide
      association studies (GWAS) in vasculitis have been published, in Behcet's disease
      and Kawasaki disease; none of the genes identified in these studies had been
      previously investigated. Associations of various HLA alleles with different
      vasculitides have been replicated. Other genes associated with Wegener's
      granulomatosis in replicated candidate gene studies are also associated with
      other autoimmune diseases. Consistent with this finding, epidemiologic data
      suggest a familial link between risk of Wegener's granulomatosis and rheumatoid
      arthritis. Among the most interesting genes clearly associated with vasculitis,
      however, are uncommon alleles that also cause monogenic recessive diseases: MEFV
      in Behcet's disease and Henoch-Schonlein purpura, and A1AT in Wegener's
      granulomatosis. SUMMARY: At the same time as candidate gene studies in vasculitis
      are identifying both common polymorphisms associated with other autoimmune
      diseases and rare alleles associated with recessive inherited diseases, early
      GWAS results are identifying completely different associations. The tools are
      available to more comprehensively delineate the genetic component of risk for
      these rare diseases.

PMID- 20051863
TI  - A roadmap for education to improve the quality of care in gout.
AB  - PURPOSE OF REVIEW: To describe obstacles to optimum management of gout by primary
      care physicians and to propose educational interventions to improve care. RECENT
      FINDINGS: In the past, gout education has been hampered by infrequency of
      continuing medical education courses, loss of excitement for a disease in which
      therapies have not changed (until recently), insufficient evidence-based
      medicine, and the lack of motivation by physicians to re-learn this disease once
      in active practice. We identify 10 common myths that impede appropriate treatment
      of gout, identify gaps in evidence-based medicine that perpetuate those myths,
      and propose opportunities to improve education on these myths. It is through
      better gout-centered education that quality of care in gout can be enhanced.
      Residency may be one of the key points of intervention. As more evidence-based
      medicine publications address the optimum management of gout, national re
      education can occur. More outreach by community rheumatologists to primary care
      physicians through educational programs and improved referral letters can help re
      educate practitioners. Lastly, an often overlooked engine to change physician
      practices is consumer education, but current patient education programs are
      lacking. SUMMARY: Novel education interventions for physician trainees, primary
      care physicians, and patients are proposed to improve the care of patients with
      gout.

PMID- 20051864
TI  - Laparoscopic partial nephrectomy: advances since 2005.
AB  - PURPOSE OF REVIEW: Laparoscopic partial nephrectomy (LPN) technique has
      continually evolved over the last decade, resulting in better outcomes and
      increased popularity within the urological community. In this article, we provide
      an overview of the contemporary literature on LPN. RECENT FINDINGS: The technique
      of LPN has evolved over the last 5 years with a nearly 50% reduction of warm
      ischemia time in experienced hands. Complication rates have also declined such
      that morbidity and oncological outcomes are comparable to open partial
      nephrectomy, the gold standard. LPN is now an established procedure for the
      treatment of T1a renal tumors. It can also be safely performed for favorably
      located T1b tumors and more complex tumors, including hilar tumors, central
      tumors or tumors in solitary kidneys with good oncological and functional
      outcomes. SUMMARY: For renal tumors less than 4-7 cm (T1 lesions), partial
      nephrectomy is the treatment of choice. Contemporary LPN is a sophisticated
      procedure, and in expert hands, offers perioperative, functional and oncologic
      outcomes comparable to open partial nephrectomy, even for complex tumors.

PMID- 20051865
TI  - Robot-assisted partial nephrectomy: evolution and recent advances.
AB  - PURPOSE OF REVIEW: Robot-assisted partial nephrectomy (RAPN) is emerging as a
      viable complement to traditional laparoscopic and open partial nephrectomy. As a
      relatively new technique, the techniques and technologies employed during RAPN
      continue to evolve. In the present article, we provide an overview of the
      evolution of robot-assisted renal surgery, and highlight the recent advances that
      have helped to bring RAPN to the fore. RECENT FINDINGS: The learning curve for
      RAPN appears to be slight, and technical proficiency may be quickly achieved,
      even for those with limited laparoscopic experience. Recent advances include
      improvements in ergonomics of the robotic system itself, as well as the
      introduction of sliding-clip renorrhaphy, early unclamping techniques, and off
      clamp techniques. Early-to-intermediate outcomes are very promising,
      demonstrating short warm ischemic times, and a low rate of complication and
      recurrence. Disadvantages to the approach include substantial cost, as well as
      increased reliance upon the assistant to perform critical maneuvers. SUMMARY:
      Robot-assisted partial nephrectomy appears to be a safe and efficacious technique
      for the surgical management of localized renal malignancy. Recent developments
      have focused upon reducing ischemic insult, as well as decreasing reliance upon
      the assistant.

PMID- 20051867
TI  - Re: awake orotracheal intubation with the Bonfils fiberscope in patients with a
      difficult airway.

PMID- 20051868
TI  - Postconditioning by xenon and hypothermia in the rat heart in vivo.
AB  - BACKGROUND AND OBJECTIVE: Hypothermia protects against myocardial reperfusion
      injury. However, inducing hypothermia takes time, which makes it unsuitable as an
      emergency treatment. Combining mild hypothermia with low-dose xenon, applied
      either simultaneously or one after the other, protects the neonatal rat brain
      against reperfusion injury. We investigated whether xenon, administered prior to
      hypothermia or simultaneously with hypothermia, also protects the rat heart from
      reperfusion injury. METHODS: Anaesthetized rats (chloralose, ketamine, diazepam)
      were randomly allocated to five groups and subjected to 25 min coronary artery
      occlusion, followed by 120 min reperfusion. At the onset of reperfusion, controls
      received no intervention and inhaled oxygen in air with an inspired oxygen
      fraction of 0.8 (Con80). Further groups received either 1 h of mild hypothermia
      of 34 degrees C (Hypo34) or 30 min of xenon 20% (Xe20). Additional groups
      received xenon 20% and hypothermia 34 degrees C simultaneously (Xe20 + Hypo34) or
      in succession (Xe20-->Hypo34). Infarct sizes were assessed by
      triphenyltetrazolium chloride staining. RESULTS: The combination of xenon 20% and
      hypothermia 34 degrees C significantly reduced infarct size [Xe20 + Hypo34:
      55(22)%, mean (SD)] compared with control [Con80: 76(12)%, P = 0.03]. Xenon and
      hypothermia in succession produced no infarct size reduction. CONCLUSION: The
      combination of xenon 20% and hypothermia of 34 degrees C, applied during early
      reperfusion, reduces infarct size in the rat heart in vivo.

PMID- 20051869
TI  - Alcohol consumption and risk of cardiovascular disease among hypertensive women.
AB  - AIM: This study investigated the relation between alcohol consumption and the
      risk of cardiovascular disease (CVD) among 10 530-hypertensive women from the
      EPIC-NL cohort. METHODS AND RESULTS: Alcohol consumption was assessed using a
      validated food-frequency questionnaire and participants were followed for
      occurrence of CVD. During 9.4 years follow-up, we documented 580 coronary heart
      disease (CHD) events and 254 strokes, 165 of which were ischemic. An inverse
      association (Ptrend=0.009) between alcohol consumption and risk of CHD was
      observed with a multivariate-adjusted hazard ratio of 0.72 (95% confidence
      interval: 0.52-1.01) for those consuming 70-139.9 g alcohol/week compared to
      lifetime abstainers. Of different beverages, only red wine consumption was
      associated with a reduced risk of CHD. A U-shaped relation (P=0.08) was observed
      for total stroke with a hazard ratio of 0.65 (0.44-0.95) for consuming 5-69.9 g
      alcohol/week compared with lifetime abstainers. Similar results were observed for
      ischemic stroke with a hazard ratio of 0.56 (0.35-0.89) for consuming of 5-69.9 g
      alcohol/week. CONCLUSION: We conclude that moderate alcohol consumption is
      associated with a reduced risk of CHD among hypertensive women. Light alcohol
      consumption tended to be related to a lower risk of stroke. Current guidelines
      for alcohol consumption in the general population also apply to hypertensive
      women.

PMID- 20051870
TI  - Safety of early exercise training after elective coronary stenting in patients
      with stable coronary artery disease.
AB  - BACKGROUND: Early exercise after coronary stenting is considered to have a risk
      of stent thrombosis (ST). We investigate the safety of submaximal exercise
      training based on the Borg scale from the next day after coronary stenting.
      METHODS: We enrolled 2351 patients who underwent successful coronary stenting.
      They were divided into early exercise training (EET) group (n=865) and control
      group (n=1486). Submaximal exercise training based on the Borg scale was
      performed on the next day after coronary stenting and same degree exercise was
      continued more than two times a week after discharge. Primary endpoint was the
      incidence of ST. Secondary endpoint was major adverse cardiovascular event
      (death, myocardial infarction, and stroke), incidence of postoperative
      complications, and rate of exercise continuation. RESULTS: Exercise training was
      performed in 800 (92.5%) patients. No serious complication developed during and
      after exercise. Clinical follow-up data were obtained in 99% patients. At 30
      days, there was no significant difference in the incidence of ST (0.58 vs. 0.47%,
      P=0.73), major adverse cardiovascular event (1.4 vs. 1.3%, P=0.72), and
      complication rate (6.9 vs. 7.3%, P=0.72). No exercise-related ST was found in
      either group. The rate of exercise continuation was significantly higher in the
      EET group (49.3 vs. 28.3%, P<0.001). CONCLUSION: EET up to submaximal level based
      on the Borg scale from the day after elective coronary stenting does not increase
      the incidence of ST or postoperative complications.

PMID- 20051871
TI  - Prepubertal genistein exposure affects erbB2/Akt signal and reduces rat mammary
      tumorigenesis.
AB  - Breast cancer is the most common malignancy in women worldwide and pharmaceutical
      agents have therapeutic and preventive effects in breast cancer. The human
      epidermal growth factor receptor 2/neu is one of the most important oncogenes in
      human breast cancer. Prepubertal exposure to endogenous estradiol and a
      phytoestrogen, genistein (Gen), has been shown to reduce future breast cancer
      risk. Gen downregulates tyrosine kinase regulated protein expression and reduces
      prostate cancer. In this study, the effects of prepubertal exposure to Gen on rat
      mammary carcinogenesis and the erbB2/Akt signal pathway were investigated.
      Prepubertal female Sprague-Dawley rats were daily exposed to Gen at 125 mg/kg
      (Gen-1) and 500 mg/kg (Gen-5) from postnatal days 22-28. Subsequently, the rats
      were given a single dose of 100 mg/kg 7.12-dimethylbenz [a] anthracene on
      postnatal day 42 to induce mammary tumor. The mRNA expression of erbB2 and
      amplified in breast cancer 1 (AIB1) was detected by reverse transcription
      polymerase chain reaction. The protein levels of proliferating cell nuclear
      antigen (PCNA), erbB2, phosphotyrosine protein, Akt, and p-Akt were detected by
      immunohistochemistry and Western blotting. The activity of protein tyrosine
      kinase (PTK) was detected by liquid scintillation counting. The percentage of
      rats with mammary tumors in breast cancer model (BCM), Gen-1, and Gen-5 was
      71.43, 52.38, and 33.34%, respectively. The incidence of 7.12-dimethylbenz [a]
      anthracene-induced mammary tumors significantly decreased in Gen-5 compared with
      that in BCM. The mRNA levels of AIB1 and erbB2 and the protein levels of erbB2, p
      Akt, and PCNA protein expression were downregulated for a long time in the
      mammary tumors in Gen-5 groups. The activity of PTK was also decreased for a long
      time. However, the total Akt protein expression did not change significantly
      among BCM, Gen-1, and Gen-5. Prepubertal exposure of Sprague-Dawley female rats
      to 500 mg/kg Gen can reduce later breast cancer risk and its protective effect is
      associated with persistent downregulation of the expression of erbB2, p-Akt,
      AIB1, and PCNA and with low PTK activity in the mammary tumor. Our results
      suggest that erbB2/Akt signaling plays a role in tumor formation and targeting
      erbB2/Akt signaling with prepubertal exposure to Gen may provide greater efficacy
      to the current therapies used to treat tumors.

PMID- 20051872
TI  - Breast cancer mortality trends and patterns in Cordoba, Argentina in the period
      1986-2006.
AB  - To estimate the mortality trends and spatial patterns for breast cancer in
      Cordoba (Argentina) in the period 1986-2006 taking into account age, calendar
      year, and birth cohort effects. Mortality data were provided by the Department of
      Statistics, Ministry of Health of Cordoba. Time trends in breast cancer mortality
      were analyzed using joinpoint analysis and age-period-cohort models. A random
      intercept log-linear model was also used to assess the spatial pattern. Breast
      cancer age standardized mortality rates rose by 1.4% (95% confidence interval 0.2
      2.6) per year from 1986 to 1997, and thereafter both breast and total cancer
      rates declined [-2.5% (-4 to -1.0) and -1.6% (-2.3 to -0.8), respectively]. In
      age-specific analysis the decline was mainly at age 20-49 years [-2.4% (-4 to 
      0.9)]. Rates over most recent calendar years decreased, mainly in the most
      urbanized districts. Age-period-cohort models for Cordoba province and Cordoba
      Capital showed a favorable cohort effect for generations born after 1955. A
      decreasing trend in breast cancer mortality was found in Cordoba, especially at
      younger ages and in most urbanized areas. This could be attributed to some
      unidentified favorable factors in generations born after 1955.

PMID- 20051873
TI  - Acute infection of Chinese macaques by a CCR5-tropic SHIV carrying a primary HIV
      1 subtype B' envelope.
AB  - The increasing prevalence of HIV-1 subtype B' in China and Southeast Asia calls
      for efforts to develop a relevant animal model to study viral transmission and
      pathogenesis. Because there are significant differences between subtype B' HIV-1
      and other chimeric simian/human immunodeficiency viru (SHIVs) in the env gene, a
      novel SHIV, designated SHIV(B'WHU), was generated by replacing counterparts of
      SHIV(SF33) with tat/rev/vpu/env genes derived from a primary, CCR5-tropic,
      subtype B' HIV-1 strain of a Chinese patient. SHIV(B'WHU) was able to replicate
      in rhesus peripheral blood mononuclear cells and used CCR5 as its major
      coreceptor. Moreover, after serial passages in Chinese macaques, the in vivo
      infectivity of SHIV(B'WHU) was enhanced, yet no significant sequence changes were
      found in viral envelopes, and the virus did not change its CCR5-tropism. CD4(+) T
      cell loss, however, was found in the intraepithelial lymphocytes of small
      intestines of infected macaques. Our findings have implications in understanding
      the early pathogenesis of SHIV(B'WHU) in Chinese macaques.

PMID- 20051874
TI  - Pairwise comparison of isogenic HIV-1 viruses: R5 phenotype replicates more
      efficiently than X4 phenotype in primary CD4+ T cells expressing physiological
      levels of CXCR4.
AB  - CCR5-using (R5) HIV-1 strains are present during the whole course of the
      infection in all subjects, whereas CXCR4-using (X4) HIV-1 strains appear only in
      the late stages of the infection in some subjects. In this study, we tested the
      hypothesis that this phenomenon might be the result of a replicative advantage of
      R5 over X4 strains. We compared the infectivity of an R5 and an X4 strain that
      differ only in their env gene in peripheral blood mononuclear cells. CD4 T cells
      in culture, where the CXCR4 ligand SDF-1 is absent, overexpress CXCR4 at their
      surface. Therefore, a cell line producing the chemokine SDF-1, that binds to and
      induces the internalization of CXCR4, was established by transfer of the SDF-1
      gene. We cocultured peripheral blood mononuclear cells with this SDF-1-producing
      cell line to obtain SDF-1 concentrations that maintained the CD4 T cell surface
      CXCR4 densities observed in vivo. Under these conditions, the R5 strain appeared
      to replicate more efficiently than the X4 strain. Thus, in vitro, when CD4 T
      cells express physiological levels of CXCR4 coreceptors, R5 virions are more fit
      for replication than X4 virions and in vivo that limited surface expression of
      CXCR4 on cell targets could contribute to the preponderance of R5 viruses.

PMID- 20051875
TI  - NT pro-B-type natriuretic peptide levels are related to microvascular reperfusion
      in patients undergoing direct percutaneous transluminal coronary angioplasty for
      anterior ST-segment elevation myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to describe the time course of NT pro-B
      type natriuretic peptide (NT pro-BNP) levels in patients with large anterior ST
      segment elevation myocardial infarction (STEMI) treated with primary angioplasty
      (PPCI) and to investigate the relationship between these values and both
      microvascular reperfusion and left ventricular (LV) function. BACKGROUND: The
      clinical efficacy of PPCI is largely dependent on the achievement of
      microvascular reperfusion. Myocardial blush is an angiographic method to evaluate
      the presence of effective reperfusion after PPCI. NT pro-BNP is a biomarker of LV
      stress whose levels are also related to clinical outcome in STEMI. METHODS: We
      studied 84 patients with large anterior STEMI treated with PPCI. NT pro-BNP was
      measured at baseline, after 2 days (day 2) and 7 days (day 7). Echocardiographic
      LV ejection fraction (LVEF) was measured at baseline, day 7 and after 6 months.
      Myocardial blush was graded immediately after PPCI. RESULTS: NT pro-BNP increased
      from admission to day 2 and decreased from day 2 to day 7 in patients with
      significant myocardial blush (grade 2-3) as well as in patients with 0-1
      myocardial blush. However, in the latter group median NT pro-BNP levels globally
      increased from admission to day 7, whereas they decreased in patients with
      significant myocardial blush. Moreover, in such patients LVEF was higher at all
      time points than in patients with a grade 0-1 myocardial blush. CONCLUSION: This
      study shows that the time course of NT pro-BNP in the first week after an
      anterior STEMI is dependent on the effectiveness of microvascular reperfusion
      assessed after PPCI and reflects the evolution of LVEF over time.

PMID- 20051876
TI  - Effect of statins on the viability of macrophages and smooth muscle cells.
AB  - Because macrophages play an important role in the destabilization of
      atherosclerotic plaques, and smooth muscle cells (SMCs) contribute to plaque
      stability, selective clearance of macrophages in atherosclerotic plaques is a
      promising strategy for plaque stabilization. In the present study, we
      investigated the effects of fluvastatin, simvastatin, lovastatin, and pravastatin
      on the viability of macrophages and SMCs. All statins, except pravastatin,
      induced cell death of J774A.1 macrophages after 24 hours, albeit with different
      sensitivity. The viability of rabbit aortic SMCs was hardly affected. Fluvastatin
      induced macrophage cell death was characterized as apoptosis and could be
      reversed by isoprenoid intermediates of the mevalonate pathway. Peritoneal
      macrophages from male or female mice were much more resistant to statin-induced
      cell death. The high sensitivity of J774A.1 macrophages to statin-induced cell
      death was related to the strong 3-hydroxy-3-methylglutaryl coenzyme A reductase
      activity in these cells. Macrophage and SMC content of rabbit atherosclerotic
      plaques was not affected after in vitro treatment with fluvastatin or lovastatin
      for 3 days. In conclusion, fluvastatin, simvastatin, and lovastatin, but not
      pravastatin, can selectively induce apoptosis in J774A.1 macrophages, but not in
      SMCs, primary macrophages or rabbit atherosclerotic plaques. This effect was
      related to the degree of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity
      in the different cell types.

PMID- 20051877
TI  - How to protect doxorubicin-induced cardiomyopathy in male albino rats?
AB  - The present study was designed to compare the cardioprotective effects of the
      combination of lisinopril with growth hormone over lisinopril alone in
      doxorubicin (Dox)-induced cardiomyopathy in rats. Forty male Wister albino rats
      were divided into 4 groups: group 1, control group; group 2, received Dox; group
      3, received lisinopril + Dox; and group 4, received lisinopril + Dox + growth
      hormone. Dox (cumulative dose) was administered to rats in 6 equal
      intraperitoneal injections over a period of 2 weeks. Histopathological changes
      and plasma aspartate aminotransferase, lactate dehydrogenase, and creatine kinase
      and plasma levels of matrix metalloproteinase (MMP)-2, tissue inhibitor matrix
      metalloproteinase (TIMP)-1, and cardiac inducible nitric oxide synthase (iNOS)
      messenger RNA (mRNA) expression were determined 9 weeks after the first dose of
      Dox. Dox produced cardiac structural injury and significant elevation in plasma
      levels of cardiac enzymes, MMP-2, and cardiac iNOS mRNA expression together with
      significant reduction in plasma TIMP-1 level. Lisinopril significantly decreases
      plasma MMP-2 level and cardiac iNOS mRNA expression by 13% and 15%, respectively,
      in group 3 compared with 36% and 47%, respectively, in group 4 as compared with
      group 2. In addition, compared with Dox group, lisinopril significantly increases
      plasma TIMP-1 level by 23% compared with 49% in group 4. We can conclude that the
      combination of lisinopril and growth hormone produced better cardioprotective
      effect against Dox-induced cardiomyopathy. This effect may be attributed on their
      antiremodeling actions by regulating plasma MMP-2/TIMP-1 levels and to the
      reduction of cardiac iNOS mRNA expression.

PMID- 20051878
TI  - Long-term effects of growth hormone on infarct size and left ventricular function
      in sheep with coronary artery occlusion.
AB  - The effects of growth hormone (GH) on infarct size and left ventricular (LV)
      function in experimental acute myocardial infarction (AMI) have been
      controversial. Moreover, little, if any, information exists regarding long-term
      evaluation of therapeutic doses of GH in large mammalian models of AMI. We
      therefore aimed to assess the effect of therapeutic doses of GH over 3.5 months
      on infarct size and heart function in sheep with AMI. After coronary artery
      ligation, sheep received subcutaneous human GH 8 IU/d (n = 8) or vehicle (n = 8)
      over 100 days. Infarct area was similar in GH (16.9% +/- 3% of LV area) and
      placebo (16.5% +/- 3.7%, P = not significant) sheep. At 3 days of treatment
      onset, but not at later times, GH sheep had higher LV shortening fraction (30.7%
      +/- 3.5% vs. 24.8% +/- 6.1%, P < 0.04), systolic anterior wall thickness (10.1 +/
      0.8 vs. 8.6 +/- 1.2 mm, P < 0.02), and cardiac index (3.8 +/- 0.6 vs. 2.8 +/-
      0.7 L x min x m, P < 0.01). This evolution of function parameters paralleled that
      of serum insulin-like growth factor 1 levels, which differed significantly only
      during the first week, suggesting a direct effect of GH on LV contractility.
      These results may suggest the usefulness of therapeutic doses of GH at the early
      phases of AMI but do not support maintaining the treatment for longer time.

PMID- 20051879
TI  - Torcetrapib produces endothelial dysfunction independent of cholesteryl ester
      transfer protein inhibition.
AB  - OBJECTIVE: Torcetrapib, a prototype cholesteryl ester transfer protein (CETP)
      inhibitor with potential for decreasing atherosclerotic disease, increased
      cardiovascular events in clinical trials. The identified hypertensive and
      aldosterone-elevating actions of torcetrapib may not fully account for this
      elevated cardiovascular risk. Therefore, we evaluated the effects of torcetrapib
      on endothelial mediated vasodilation in vivo. METHODS AND RESULTS: In vivo
      endothelial mediated vasodilation was assessed using ultrasound imaging of
      acetylcholine-induced changes in rabbit central ear artery diameter. Torcetrapib,
      in addition to producing hypertension and baseline vasoconstriction, markedly
      inhibited acetylcholine-induced vasodilation. A structurally distinct CETP
      inhibitor, JNJ-28545595, did not affect endothelial function despite producing
      similar degrees of CETP inhibition and high-density lipoprotein elevation.
      Nitroprusside normalized torcetrapib's basal vasoconstriction and elicited dose
      dependent vasodilation of norepinephrine preconstricted arteries in torcetrapib
      treated animals, indicating torcetrapib did not impair smooth muscle function.
      CONCLUSIONS: Torcetrapib significantly impairs endothelial function in vivo,
      independent of CETP inhibition and high-density lipoprotein elevation. Given the
      well-documented association of endothelial dysfunction with cardiovascular
      disease and risk, this activity of torcetrapib may have contributed to increased
      cardiovascular risk in clinical trials.

PMID- 20051881
TI  - Phacotrabeculectomy without mitomycin C in primary angle-closure and open-angle
      glaucoma.
AB  - PURPOSE: To compare the surgical outcomes of single site phacotrabeculectomy
      without mitomycin C (MMC) in primary angle-closure glaucoma (PACG) and primary
      open-angle glaucoma (POAG). METHODS: We retrospectively reviewed the records of
      all patients with a diagnosis of PACG and POAG, who underwent single site
      phacotrabeculectomy without MMC between January 2001 and December 2005 and had a
      minimum follow-up of 12 months. The primary outcome measure was cumulative
      success probability, defined as complete [intraocular pressure (IOP) <=21 mm Hg
      without antiglaucoma medications or additional surgery] and qualified (IOP <21 mm
      Hg with medications). Secondary outcome measures were reduction of IOP, the
      number of antiglaucoma medications at last follow-up, and complication rates.
      RESULTS: Seventy-one eyes of 63 PACG patients (mean age 61.2 y) and 72 eyes of 57
      POAG patients (mean age 64.0 y) were analyzed. Mean duration of follow-up was
      38.7 and 41.7 months in the PACG and POAG groups, respectively. Complete success
      in PACG (72.1%) was more than the POAG group (56.1%), but the difference was not
      statistically significant (P=0.06). Qualified success in the PACG and POAG group
      was 87.4% and 92.8%, respectively (P=0.43). IOP reduction was greater (P=0.03) in
      the PACG group and PACG group required fewer antiglaucoma medications
      postoperatively (P=0.03) for IOP control. CONCLUSIONS: Survival probability of
      single site phacotrabeculectomy without MMC was not significantly different
      between the PACG and POAG groups. IOP reduction was greater and the need for
      antiglaucoma medications after surgery was lesser in the PACG group.

PMID- 20051880
TI  - Uncoupling the coupled calcium and zinc dyshomeostasis in cardiac myocytes and
      mitochondria seen in aldosteronism.
AB  - Intracellular [Ca2+]i overloading in cardiomyocytes is a fundamental pathogenic
      event associated with chronic aldosterone/salt treatment (ALDOST) and accounts
      for an induction of oxidative stress that leads to necrotic cell death and
      consequent myocardial scarring. This prooxidant response to Ca2+ overloading in
      cardiac myocytes and mitochondria is intrinsically coupled to simultaneous
      increased Zn2+ entry serving as an antioxidant. Herein, we investigated whether
      Ca2+ and Zn2+ dyshomeostasis and prooxidant to antioxidant dysequilibrium seen at
      4 weeks, the pathologic stage of ALDOST, could be uncoupled in favor of
      antioxidants, using cotreatment with a ZnSO4 supplement; pyrrolidine
      dithiocarbamate (PDTC), a Zn2+ ionophore; or ZnSO4 in combination with amlodipine
      (Amlod), a Ca2+ channel blocker. We monitored and compared responses in
      cardiomyocyte free [Ca2+]i and [Zn2+]i together with biomarkers of oxidative
      stress in cardiac myocytes and mitochondria. At week 4 of ALDOST and compared
      with controls, we found (1) an elevation in [Ca2+]i coupled with [Zn2+]i and (2)
      increased mitochondrial H2O2 production and increased mitochondrial and cardiac 8
      isoprostane levels. Cotreatment with the ZnSO4 supplement alone, PDTC, or
      ZnSO4+Amlod augmented the rise in cardiomyocyte [Zn2+]i beyond that seen with
      ALDOST alone, whereas attenuating the rise in [Ca2+]i, which together served to
      reduce oxidative stress. Thus, a coupled dyshomeostasis of intracellular Ca2+ and
      Zn2+ was demonstrated in cardiac myocytes and mitochondria during 4-week ALDOST,
      where prooxidants overwhelm antioxidant defenses. This intrinsically coupled Ca2+
      and Zn2+ dyshomeostasis could be uncoupled in favor of antioxidant defenses by
      selectively increasing free [Zn2+]i and/or reducing [Ca2+]i using cotreatment
      with ZnSO4 or PDTC alone or ZnSO4+Amlod in combination.

PMID- 20051882
TI  - Is there a correlation between diabetes mellitus and central corneal thickness?
AB  - PURPOSE: To evaluate the association of central corneal thickness (CCT) with
      diabetes mellitus and compare it with age and sex-matched healthy controls.
      MATERIALS AND METHODS: This study included 245 eyes of 245 subjects (one eye per
      subject). One hundred diabetic patients constituted the study group and 145 were
      healthy controls. The study group was subdivided into 3 subgroups: subgroup 1 (no
      diabetic retinopathy), subgroup 2 (nonproliferative diabetic retinopathy), and
      subgroup 3 (proliferative diabetic retinopathy). CCT was determined with
      ultrasonic pachymeter. None of the patients had glaucoma, retinal laser
      treatment, and history of ocular surgery. Statistical analyses were performed by
      analysis of variance and Kruskall-Wallis tests. Correlation analysis was
      performed to assess the association between disease duration and glycosylated
      hemoglobin levels among subgroups. RESULTS: Demographic characteristics of study
      and control groups were similar (P>0.05). The mean CCT was significantly greater
      in study group (564+/-30 MUm) compared with control group (538+/-35 MUm)
      (P=0.001). In addition, mean CCT was found to be greater in subgroup 3 (582+/-23
      MUm) compared with subgroups 1 (565+/-32 MUm) and 2 (558+/-31 MUm); but the
      difference did not reach statistical significance (P=0.056). Also, there was no
      significant correlation in respect to the level of glycosylated hemoglobin and
      disease duration among the subgroups. CONCLUSIONS: We found that the central
      cornea of diabetic patients is thicker when compared with nondiabetic patients.
      Thicker central cornea associated with diabetes mellitus should be taken into
      consideration while obtaining accurate intraocular pressure measurements in
      diabetics.

PMID- 20051883
TI  - Optic disc damage staging system.
AB  - PURPOSE: To evaluate the optic disc damage staging system (ODDSS); a new clinical
      method of optic disc (OD) classification based on OD size, neural rim (NR) loss
      severity and localization. Accuracy, reproducibility, and reliability were
      studied. Agreement of ODDSS with the Heidelberg-Retina-Tomograph (HRT) results
      was evaluated. METHODS: One eye of 68 consecutive open-angle glaucoma (POAG)
      patients and 40 controls underwent standard automated perimetry (SAP), HRT-II,
      and OD examination using the ODDSS classification by 3 independent graders in
      this prospective cross-sectional study. Sensitivity, specificity, and area under
      the receiver operating characteristic curve (AROC) in discriminating between
      normal and POAG eyes were determined for ODDSS and HRT parameters. ODDSS
      intraobserver and interobserver agreement and agreement with HRT-Moorfield
      Regression-Analysis (MRA) were assessed. RESULTS: ODDSS sensitivity ranged from
      72.0% to 89.7%; specificity ranged from 92.5% to 100%. Differences between AROCs
      for ODDSS (0.89 to 0.94) and for the best-performing HRT parameter (Vertical
      Cup/Disc Ratio 0.88) were not statistically significant. ODDSS interobserver
      agreement ranged from 0.33 to 0.78; intraobserver agreement ranged from 0.53 to
      0.89. Agreement with HRT-MRA ranged from 0.50 to 0.87. CONCLUSIONS: ODDSS is a
      new method for assessing, recording, and sharing information about the clinical
      OD appearance. Our preliminary results show that it provides good sensitivity and
      specificity in glaucoma detection. The interobserver and intraobserver agreement
      ranged from fair to good.

PMID- 20051884
TI  - Anterior chamber blood reflux during trabeculectomy in an eye with previous
      trabectome surgery.
AB  - INTRODUCTION: The Trabectome is a novel surgical device used in the treatment of
      open angle glaucoma that removes trabecular meshwork tissue to improve aqueous
      access to drainage channels. Little is known about the long-term consequences of
      permanently unroofing Schlemm canal. Eyes that have had previous surgery in the
      iridocorneal angle, specifically permanent removal of trabecular meshwork tissue,
      may have an increased propensity for blood reflux. CASE PRESENTATION: We present
      a case of a patient who had intraoperative blood reflux onto peripheral iris
      during trabeculectomy 11 months after Trabectome surgery. DISCUSSION:
      Intraoperative blood reflux and resultant hyphema is strongly correlated with
      Trabectome surgery, but the literature does not reveal any cases of late
      postoperative blood reflux. In our patient, the absence of overlying angle
      structures, including the roof of Schlemm canal, may have allowed blood to reflux
      into the angle and onto peripheral iris during a sudden decrease in intraocular
      pressure in trabeculectomy surgery. Further studies to assess the consequences of
      permanent trabecular meshwork tissue removal may be warranted.

PMID- 20051885
TI  - Application of handheld cautery for reduction of symptomatic circumferential
      trabeculectomy blebs.
AB  - PURPOSE: To describe a new, in-office procedure for limiting symptomatic,
      circumferential conjunctival blebs occurring after trabeculectomy. PATIENTS: Two
      eyes of 2 patients status postfornix-based trabeculectomy with mitomycin C were
      found to have symptomatic circumferential blebs. METHODS: Risks and benefits of
      cautery were discussed, along with alternatives including continued conservative
      treatment or surgical revision. The patients opted for in-office cautery. Two
      eyes of 2 patients underwent cauterization of their blebs with a Bovie high
      temperature handheld cautery in the office after topical pretreatment with 2.5%
      neosynephrine and 4% xylocaine. Excess fluid was drained from the bleb by
      expression through the puncture wounds. The wounds were Seidel negative
      immediately after the treatment. RESULTS: Flattening of the bleb occurred
      instantly, patients did not experience pain and their symptoms related to the
      extensive bleb resolved. The functioning of the bleb was not altered in these 2
      cases by this procedure. CONCLUSIONS: Early results show that handheld cautery
      may be a useful means of treating symptomatic circumferential blebs.

PMID- 20051886
TI  - Lack of association of polymorphisms in elastin with pseudoexfoliation syndrome
      and glaucoma.
AB  - PURPOSE: To evaluate the elastin gene (ELN) as a secondary risk factor for
      pseudoexfoliation syndrome (PXFS) and the associated glaucoma pseudoexfoliation
      glaucoma (PXFG). METHODS: One hundred seventy-eight unrelated patients with PXFS,
      including 132 patients with PXFG, and 113 unrelated controls were recruited from
      the Massachusetts Eye and Ear Infirmary. All the patients and controls were white
      of European ancestry. Three tag SNPs (rs2071307, rs3823879, and rs3757587) that
      capture the majority of alleles in ELN were genotyped. Single-SNP association was
      analyzed using Fisher exact test. Haplotype analysis and the set-based test were
      used to assess the association for the whole gene. Interaction analysis was done
      between the ELN SNP rs2071307 and LOXL1 SNP rs2165241 using logistic regression.
      Multiple comparisons were corrected using the Bonferroni method. RESULTS: All 3
      ELN tag SNPs were not significantly associated with PXFS and PXFG (P>0.20). The
      minor allele frequencies in PXFS, PXFG, and controls were 40.7%, 39.8%, and
      45.6%, respectively for rs2071307, 6.7%, 6.3%, and 5.4% for rs3823879, and 14.8%,
      16.2%, and 13.6% for rs3757587. Haplotype analysis and the set-based test did not
      find significant association of ELN with PXFS (P=0.94 and 0.99, respectively). No
      significant interaction effects on PXFS were identified between the ELN and LOXL1
      SNPs (P=0.55). CONCLUSIONS: Our results suggest that common polymorphisms of ELN
      are not associated with PXFS and PXFG in white populations. Further studies are
      required to identify secondary genetic factors that contribute to PXFS.

PMID- 20051887
TI  - Hypotensive effect of juxtascleral administration of anecortave acetate in
      different types of glaucoma.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of anecortave
      acetate, delivered by anterior juxtascleral depot injection, in eyes with various
      forms of glaucoma. METHODS: A prospective, interventional case series was carried
      out. Twenty-eight uncontrolled glaucoma patients received a single injection of
      anecortave acetate (24 to 30 mg) in 1 selected eye under topical anesthesia.
      Postinjection assessments were scheduled at week 1 and months 1, 2, and 3.
      RESULTS: Mean +/- SD age of patients was 58.2 +/- 18.6 years. Twelve patients had
      open-angle glaucoma and 16 had angle-closure glaucoma. Uveitic/steroid-induced
      glaucoma was the most frequent diagnosis (11 patients, 39.2%). Mean baseline IOP
      was 30.7 +/- 9.3 mm Hg. Mean IOP at week 1 and months 1, 2, and 3 were 21.3 +/-
      6.1, 19.8 +/- 6.3, 20.9 +/- 7.3, and 21.7 +/- 6.8 mm Hg, respectively.
      Significant mean IOP reductions were observed at week 1 and months 1, 2, and 3
      (29.3%, 33.8%, 30.1%, and 27.2%, respectively; P<0.001). CONCLUSION: A single
      administration of anecortave acetate by anterior juxtascleral depot injection
      seems to result in a significant IOP reduction (compared with baseline) for at
      least 3 months in eyes with different types of glaucoma. No injection-related or
      drug-related serious adverse events were observed. Additional studies are
      required to better determine the efficacy, safety, and mechanism of action of
      this alternative treatment.

PMID- 20051888
TI  - Retinal nerve fiber layer thickness in normals measured by spectral domain OCT.
AB  - PURPOSE: To determine normal values for peripapillary retinal nerve fiber layer
      thickness (RNFL) measured by spectral domain Optical Coherence Tomography (SOCT)
      in healthy white adults and to examine the relationship of RNFL with age, gender,
      and clinical variables. PATIENTS AND METHODS: The peripapillary RNFL of 170
      healthy patients (96 males and 74 females, age 20 to 78 y) was imaged with a high
      resolution SOCT (Spectralis HRA+OCT, Heidelberg Engineering) in an observational
      cross-sectional study. RNFL thickness was measured around the optic nerve head
      using 16 automatically averaged, consecutive circular B-scans with 3.4-mm
      diameter. The automatically segmented RNFL thickness was divided into 32 segments
      (11.25 degrees each). One randomly selected eye per subject entered the study.
      RESULTS: Mean RNFL thickness in the study population was 97.2 +/- 9.7 MUm. Mean
      RNFL thickness was significantly negatively correlated with age (r = -0.214, P =
      0.005), mean RNFL decrease per decade was 1.90 MUm. As age dependency was
      different in different segments, age-correction of RNFL values was made for all
      segments separately. Age-adjusted RNFL thickness showed a significant correlation
      with axial length (r = -0.391, P = 0.001) and with refractive error (r = 0.396,
      P<0.001), but not with disc size (r = 0.124). CONCLUSIONS: Normal RNFL results
      with SOCT are comparable to those reported with time-domain OCT. In accordance
      with the literature on other devices, RNFL thickness measured with SOCT was
      significantly correlated with age and axial length. For creating a normative
      database of SOCT RNFL values have to be age adjusted.

PMID- 20051889
TI  - The effect of phacoemulsification cataract surgery on polarimetry and tomography
      measurements for glaucoma diagnosis.
AB  - PURPOSE: To assess whether optical coherence tomography (OCT)Stratus 3000,
      confocal laser scanning ophthalmoscopy (HRT3), and scanning laser polarimetry
      (GDx-VCC) results show parameter differences between presurgery and postsurgery
      in patients with cataracts and suspected glaucoma. SETTING: Glaucoma Service in
      the Department of Ophthalmology at the Miguel Servet University Hospital,
      Zaragoza, Spain. METHODS: Forty-six eyes of 46 patients were enrolled in this
      cross-sectional study and examined with OCT, HRT3, and GDx-VCC before and after
      phacoemulsification. Differences between presurgery and postoperative
      measurements were calculated using nonparametric test. RESULTS: The most
      significant difference between the study groups was in the OCT image quality; the
      signal-to-noise ratio improved from presurgery to postsurgery. All of the
      statistically significant sectors reflected measurements in the nasal region and
      the maximum superior and average nasal retinal nerve fiber layer (thickness
      (Smax/Navg). Almost all parameters of the HRT area remained unchanged after the
      surgery, but important differences were observed in cup depth, volume parameters,
      and image quality. The Glaucoma Progression Score feature may not be helpful in
      the presence of lens opacity. Temporal incision during the surgery affected most
      of the nasal GDx-VCC parameters and the image quality. CONCLUSIONS: OCT image
      quality was reduced preoperatively in the eyes with cataracts and retinal nerve
      fiber layer thickness in the nasal sectors was increased in these eyes
      postoperatively. Cup depth, volume parameters, Glaucoma Progression Score, and
      the image quality of HRT measurements were all influenced by cataract removal. In
      our study temporal incision during surgery affected the nasal parameters in GDx
      VCC. Our results suggest that the examiner should consider obtaining a new
      baseline measurement after cataract surgery.

PMID- 20051890
TI  - Prostaglandin efficacy and safety study undertaken by race (the PRESSURE study).
AB  - PURPOSE: Latanoprost, travoprost, and bimatoprost are prostaglandin or prostamide
      type ocular hypotensive medications, all of which are effective and safe for
      lowering intraocular pressure (IOP). Most studies with these types of drugs have
      included patients mainly from European or white ethnic backgrounds; however, some
      reports have suggested that there is a difference in response between patients of
      white and African racial heritage. On account of the possibility that drugs may
      act differently in people of different ethnic background, we decided to study the
      effectiveness and safety of all 3 drugs in people from various ethnic heritages.
      Our hypothesis was that there might be a possible ethnic-based difference in IOP
      lowering effectiveness between the 3 medications. METHOD: This was a prospective
      randomized investigator-masked multicenter study. Patients newly diagnosed with
      open-angle glaucoma (primary, pseudoexfoliative, or pigmentary), or whose
      pressure became elevated after a washout period, were randomized to receive 1 of
      3 prostaglandin/prostamide drugs. Assignment of drug was balanced by racial group
      and study site, and the investigator was masked to the drug used. The patients
      were requested to self-identify their racial group as White, African, East
      Indian, Asian, or Hispanic; to minimize the possibility of heterogeneity, all 4
      grandparents had to be known to originate from the same group. However, for
      purposes of analysis, the patients were divided into 2 groups--White or Other.
      Patients were followed at 2, 6, 12, and 24 weeks; IOP and local side effects were
      assessed at each visit. RESULTS: Eighty-three patients were recruited from 9
      sites. The mean age of the patients was 61.5 +/- 10.5 years. There were no
      differences in mean age or the distribution of sex between the patients whether
      examined by the 2 racial groups or the 3 drug groups. There was a highly
      statistically significant decrease in IOP from baseline to 12 weeks and from
      baseline to 24 weeks (F = 439.3, P<0.0001; F = 305.94, P<0.0001). There were no
      differences in treatment effect between the 3 drugs or between the 2 ethnic
      groups, (P > 0.05 for all comparisons) and there was no interaction between race
      and drug. CONCLUSIONS: All 3 prostaglandin/amide drugs are highly effective at
      lowering IOP. No differences in effect between the drugs or between members of
      different racial groups were detected, although the study sample size was too
      small to be certain to detect differences, if they existed.

PMID- 20051891
TI  - Surface tension of aqueous humor.
AB  - OBJECTIVE: To measure and compare the surface tension of aqueous humor in
      patients with and without glaucoma. METHODS: The surface tension of aqueous humor
      was measured using a commercially available instrument and software that were
      validated by using a known fluid (deionized water and methanol). Analysis of
      aqueous and vitreous samples obtained from 20 rabbit eyes showed that the system
      could be used successfully for small amounts of ocular fluid. The effect of
      glaucoma drugs on the surface tension of aqueous humor was then studied in a
      rabbit model. Comparison of aqueous humor from 66 patients with glaucoma and 53
      patients with cataracts but no glaucoma was carried out. RESULTS: The surface
      tension of rabbit aqueous humor was 65.9 +/- 1.2; vitreous, 60.6 +/- 2.6; and
      balanced salt solution, 70.7 +/- 0.9. Timolol and latanoprost did not alter the
      surface tension of the aqueous humor in the rabbit model. The average surface
      tension of human aqueous humor was 63.33 +/- 4.0 (glaucomatous eyes) and 66.19 +/
      2.64 (nonglaucomatous eyes with cataracts) (P=0.0001). CONCLUSIONS: A technique
      of measuring the surface tension from small quantities of aqueous humor is
      validated. Surface tension of the aqueous humor in glaucoma patients was less
      than that of cataract patients.

PMID- 20051892
TI  - Sturge-Weber syndrome with congenital glaucoma and cytochrome P450 (CYP1B1) gene
      mutations.
AB  - Sturge-Weber syndrome (SWS) is a progressive condition of mesodermal
      phakomatosis. This preliminary study is the first report of CYP1B1 mutation
      analysis in SWS with congenital glaucoma. PURPOSE: Mutations in CYP1B1 gene are
      the major cause of congenital glaucoma. CYP1B1 is involved in metabolism of
      melatonin, retinol, and other endogenous/exogenous substrates. Mutations in
      CYP1B1 adversely affect signal transduction pathways and thus impair
      development/differentiation of anterior segment structures. This results in
      impaired aqueous outflow. CYP1B1 has higher expression in fetal eyes and plays
      major role in morphogenesis of iris, ciliary body, and anterior chamber angle.
      Hence, we decided to evaluate SWS cases with buphthalmos for 6 most prevalent
      CYP1B1 mutations by polymerase chain reaction-restriction-fragment length
      polymorphism followed by sequencing. Trabecular meshwork was studied for
      morphological alterations by scanning electron microscopy. RESULTS: All patients
      had normal 46, XY karyotype. Polymerase chain reaction-restriction-fragment
      length polymorphism showed CYP1B1 mutations in 2 of 5 SWS cases. Scanning
      electron microscopy findings were suggestive of trabecular dysgenesis.
      DISCUSSION: No CYP1B1 mutation has been reported in any SWS case till date
      because syndromic cases were not analyzed for mutations in earlier studies.
      Earlier studies have reported that onset of glaucoma in SWS shows a bimodal
      pattern. The results from this pilot study show that SWS cases with gyral
      calcification, buphthalmos, and early onset glaucoma should be analyzed for
      CYP1B1 mutations. The effect of vascular malformation-induced venous engorgement
      and raised intraocular pressure may only be additive and may result in a much
      more severe phenotype. CONCLUSION: SWS with buphthalmos and gyral calcification
      should undergo CYP1B1 mutation analysis to identify an underlying genetic
      pathology for glaucoma. This will aid in determining the prognosis and management
      and will also help to provide comprehensive counseling in such cases.

PMID- 20051893
TI  - Autonomic dysfunction in normal tension glaucoma: the short-term heart rate
      variability analysis.
AB  - INTRODUCTION: The purpose of this study was to investigate the dysfunction of
      autonomic control that may be a contributing factor in normal tension glaucoma
      (NTG) by showing the short-term heart rate variability in NTG patients. MATERIALS
      AND METHODS: Newly diagnosed NTG patients and an age-matched normal control group
      were enrolled in this prospective study. Blood pressure was obtained and the
      electrocardiogram was monitored for 5 minutes after 30-minute rest in a supine
      position. Electrocardiographic signals were transferred to a heart rate analyzer.
      The time and frequency domain parameters of heart rate variability were analyzed
      between two groups. RESULT: In all, 77 NTG patients and 30 healthy controls were
      included in the study. There were no significant differences between NTG and
      controls with respect to age, sex, and a hypertensive history, heart rate,
      systolic pressure, and diastolic pressure. NTG patients showed a significant
      reduction in the standard deviation of the mean of qualified normal-to-normal
      intervals in comparison with controls (27.64+/-10.90 vs. 36.22+/-10.21, P=0.041).
      Low-frequency values in NTG patients were statistically lower than in healthy
      controls (P=0.001) and the low-frequency/high-frequency ratio was significantly
      higher in the NTG group (P=0.000). DISCUSSION: Our study results showed that the
      dysfunction of an autonomic control is associated with NTG patients.

PMID- 20051894
TI  - Evaluation of a contact lens-embedded sensor for intraocular pressure
      measurement.
AB  - PURPOSE: To evaluate a novel contact lens-embedded pressure sensor for continuous
      measurement of intraocular pressure (IOP). METHODS: Repeated measurements of IOP
      and ocular pulse amplitude (OPA) were recorded in 12 eyes of 12 subjects in
      sitting and supine positions using 3 configurations of the dynamic contour
      tonometer: slit-lamp mounted (DCT), hand-held (HH), and contact lens-embedded
      sensor (CL). The IOP and OPA for each condition were compared using repeated
      measures ANOVA and the 95% limits of agreement were calculated. RESULTS: The
      sitting IOP (mean and 95% CI) for each configuration was DCT: 16.3 mm Hg (15.6 to
      17.1 mm Hg), HH: 16.6 mm Hg (15.6 to 17.6 mm Hg), and CL: 15.7 mm Hg (15 to 16.3
      mm Hg). The sitting OPA for each configuration was DCT: 2.4 mm Hg (2.1 to 2.6 mm
      Hg), HH: 2.4 mm Hg (2.1 to 2.7 mm Hg), and CL: 2.1 mm Hg (1.8 to 2.3 mm Hg).
      Supine IOP and OPA measurements with the CL and HH sensors were both greater than
      their corresponding sitting measurements, but were significantly less with the CL
      sensor than the HH sensor. The mean difference and 95% Limits of Agreement were
      smallest for the DCT and CL sensor comparisons (0.7+/-3.9 mm Hg) and widest for
      the CL and HH sensors (-1.9+/-7.25 mm Hg); these wider limits were attributed to
      greater HH measurement variability. CONCLUSIONS: The CL sensor was comparable to
      HH and DCT sensors with sitting subjects and is a viable method for measuring IOP
      and OPA. Supine measurements of IOP and OPA were greater than sitting conditions
      and were comparatively lower with the CL sensor. HH measurements were more
      variable than CL measurements and this influenced the Limits of Agreement for
      both sitting and supine conditions.

PMID- 20051895
TI  - The effect of sleep medications on cognitive recovery from traumatic brain
      injury.
AB  - OBJECTIVE: To summarize the literature on the available pharmacotherapy for
      insomnia and the adverse cognitive effects of those options in persons with
      traumatic brain injury (TBI). DESIGN: Ovid/MEDLINE databases were searched by
      using the following key words: "brain injury," "sleep initiation and maintenance
      disorders," "hypnotics and sedatives," "benzodiazepines," "trazodone," and
      "neuronal plasticity." RESULTS: The reviewed literature consistently reported
      that benzodiazepines and atypical gamma-aminobutyric acid (GABA) agonists result
      in cognitive impairment when plasma levels are at their peak. Evidence of
      residual effects on cognition was reported for benzodiazepines but was seen less
      often in atypical GABA agonists. However, evidence has also been presented that
      GABA agonists have adverse effects on neuroplasticity, raising concerns about
      their use in patients recovering from TBI. CONCLUSIONS: Use of benzodiazepines in
      TBI has been discouraged and some authors also advocate caution in prescribing
      atypical GABA agonists. Alternate treatments including trazodone and a newer
      class of agents, melatonin agonists, are highlighted, along with the limited data
      available addressing the use of these medications in TBI. Finally, suggestions
      are offered for further research, especially on topic related to neural
      plasticity and functional recovery.

PMID- 20051896
TI  - Residence following traumatic brain injury: a longitudinal study.
AB  - OBJECTIVE: To examine change in residence following traumatic brain injury (TBI)
      as a function of preinjury residential status, demographic factors, and injury
      related characteristics. DESIGN: Prospective, observational study. SETTING:
      Inpatient, comprehensive rehabilitation programs for persons with TBI.
      PARTICIPANTS: A total of 7925 patients with moderate or severe TBI receiving
      acute rehabilitation, and enrolled in the TBI Model Systems National Database.
      MAIN MEASURES: Preinjury and discharge residential status determined during
      rehabilitation, and at 1, 2, and 5 years postinjury by telephone interview.
      Variables contributing to residential status included injury severity,
      demographic information, and functional status. RESULTS: There was significant
      change in residence across 5 years characterized by discharge to a less
      independent residence following injury, with a return to a more independent
      residence over time. The most significant transition took place in the first year
      after injury. Residence prior to injury was the strongest predictor of residence
      after injury. Age and race were significantly associated with residence following
      TBI, with increasing age related to more independent residence, and whites more
      likely to live independently than are African Americans. Severity of injury had
      little impact, although functional status at rehabilitation discharge was
      associated with residence, with higher functional status associated with a more
      independent residence. CONCLUSION: Among persons who received acute
      rehabilitation for TBI, 35.4% were discharged from rehabilitation to a setting
      different from the one in which they resided before injury. The degree of change
      varied on the basis of preinjury residence. Overall, the results indicate that
      while many patients are discharged to a different residential setting than prior
      to their injury, some patients recover to the point where they are able to return
      to their premorbid residential setting. The most substantial change was for those
      living alone at the time of injury, and within the first year of injury.

PMID- 20051897
TI  - A controlled treatment study of internal memory strategies (I-MEMS) following
      traumatic brain injury.
AB  - OBJECTIVE: To evaluate the effects of participation in a memory group
      intervention focusing on internal strategy use on persons with traumatic brain
      injury-related memory impairment. PARTICIPANTS: Ninety-four adults with traumatic
      brain injury (54 in the experimental group and 40 controls) and resulting memory
      impairment, with severities ranging from mild to severe. All participants were at
      least 18 years of age at the time of injury and at least 1 year post injury at
      the time of study. DESIGN: Non randomized pre/posttest group comparison design.
      MAIN OUTCOME MEASURES: Hopkins Verbal Learning Test-Revised and Rivermead
      Behavioral Memory Test II. RESULTS: Participation in the memory group
      intervention was associated with improved memory performance immediately
      postintervention, and improvements were maintained 1 month postintervention.
      Severe injury was associated with less improvement in memory outcomes than mild
      and moderate injuries. Age and preinjury education were not related to outcome.
      CONCLUSIONS: Individuals with traumatic brain injury may benefit from memory
      group intervention focusing on internal strategy use. Study hypotheses should be
      retested using a randomized, controlled design, and further research is needed to
      better delineate influences on intervention candidacy and outcomes.

PMID- 20051898
TI  - Serial changes in diffusion tensor imaging metrics of corpus callosum in moderate
      traumatic brain injury patients and their correlation with neuropsychometric
      tests: a 2-year follow-up study.
AB  - OBJECTIVE: To assess longitudinally the severity of diffuse axonal injury in the
      corpus callosum in patients with moderate traumatic brain injury (TBI) through
      quantitative diffusion tensor imaging and to correlate these changes with
      neuropsychometric tests (NPT) at 6 and 24 months after injury. DESIGN:
      Prospective longitudinal study. PARTICIPANTS: Sixteen patients with TBI and 17
      age/sex-matched healthy controls. METHODS: Patients underwent magnetic resonance
      imaging at 3 time points: within 2 weeks (range = 5-14 days), 6 months, and 24
      months after injury. NPT could be performed only at 6 and 24 months. RESULTS: In
      patients with TBI, a significant increase in fractional anisotropy (FA) values in
      genu as well as an insignificant decrease in radial diffusivity (RD) and mean
      diffusivity values in genu and splenium were observed over time, respectively.
      FA, RD, and mean diffusivity values continued to be abnormal in patients compared
      with controls at the end of 2 years. Although some NPT scores improved over time
      in these patients, these were still significantly impaired compared with
      controls. CONCLUSIONS: FA and RD indices appear to be surrogate markers of
      microstructural alterations in patients over time and correlate significantly
      with some of the NPT scores. The recovery in these indices associated with
      recovery in neurocognitive deficits suggests that these indices may be used as an
      objective marker for residual injury in these patients.

PMID- 20051899
TI  - Deep white matter volume loss and social reintegration after traumatic brain
      injury in children.
AB  - OBJECTIVE: To explore whether children judged by their parents as showing an
      "excellent" or "complete" social reintegration after pediatric traumatic brain
      injury have less white matter volume (WMV) loss and better neuropsychological
      test scores than children who do not achieve this same level of reintegration.
      SETTING: Primary-care hospital/medical center. PARTICIPANTS: Twenty-eight
      children with post-acute traumatic brain injury evaluated as outpatients.
      MEASURES: Parental ratings of overall social reintegration, neuropsychological
      test performance, and voxel-based morphometry analysis of brain WMV loss.
      RESULTS: In addition to showing worse neuropsychological test performance,
      children judged not to make a complete or excellent social reintegration had
      greater WMV loss, particularly within the corpus callosum. WMV loss in the corpus
      callosum correlated with the child's Wechsler Intelligence Scale for Children
      Fourth Edition (WISC-IV) Full Scale IQ (rho = .677, P = .000) and parental
      ratings of level of social integration (rho = .415, P = .028). Admitting Glasgow
      Coma Scale scores, mother's level of education, WISC-IV Processing Speed Index
      scores, and WMV loss in the region of the corpus callosum significantly
      contributed to parental ratings of a child's level of social reintegration.
      CONCLUSIONS: Preliminary findings suggested that diffuse WMV loss, particularly
      in deep brain regions (eg, corpus callosum), may relate to the child's long-term
      psychosocial outcome as viewed from the parents' perspective.

PMID- 20051900
TI  - Mild traumatic brain injury (concussion) during combat: lack of association of
      blast mechanism with persistent postconcussive symptoms.
AB  - OBJECTIVE: To determine whether screening for a blast mechanism of concussion
      identifies individuals at higher risk of persistent postconcussive symptoms
      (PCS). SETTING: United States Army post. PARTICIPANTS: 3952 US Army infantry
      soldiers were administered anonymous surveys 3 to 6 months after returning from a
      yearlong deployment to Iraq. MAIN OUTCOME MEASURES: Self-reported concussion
      (defined as an injury that resulted in being "dazed, confused, or 'seeing
      stars'"; "not remembering the injury"; or "losing consciousness [knocked out]):
      Patient Health Questionnaire 15-item scale for physical symptoms and PCS;
      Posttraumatic Stress Disorder Checklist; and Patient Health Questionnaire
      depression module. RESULTS: Of the 587 soldiers (14.9% of the total sample) who
      met criteria for concussion, 201 (34.2%) reported loss of consciousness, and 373
      (63.5%) reported only an alteration of consciousness without loss of
      consciousness; 424 (72.2%) reported a blast mechanism, and 150 (25.6%) reported a
      nonblast mechanism. Among soldiers who lost consciousness, blast mechanism was
      significantly associated with headaches and tinnitus 3 to 6 months postdeployment
      compared with a nonblast mechanism. However, among the larger group of soldiers
      reporting concussions without loss of consciousness, blast was not associated
      with adverse health outcomes. CONCLUSIONS: Blast mechanism of concussion was
      inconsistently associated with PCS, depending on the definition of concussion
      utilized. A self-reported history of blast mechanism was not associated with
      persistent PCS for the majority of US soldiers with concussions.

PMID- 20051901
TI  - Prevalence and psychological correlates of traumatic brain injury in operation
      iraqi freedom.
AB  - OBJECTIVE: To describe the prevalence and psychological correlates of traumatic
      brain injury (TBI) among injured male combatants in the Iraq conflict.
      PARTICIPANTS: A total of 781 men injured during military combat between September
      2004 and February 2005. MAIN OUTCOME MEASURES: Mental health diagnosis (ICD-9 290
      319), particularly posttraumatic stress disorder and mood/anxiety disorders,
      assigned through November 2006. RESULTS: 15.8% met criteria for TBI (13.4% mild,
      2.4% moderate-severe TBI), 35.0% other head injury, and 49.2% non-head injury.
      Multivariate logistic regression suggested lower rates of posttraumatic stress
      disorder and mood/anxiety disorders among those with mild and moderate-severe
      TBI. CONCLUSIONS: These findings could reflect a problem with differential
      diagnosis or, conversely, a low rate of self-presentation for symptoms. Further
      research is needed to elucidate the psychological consequences, clinical
      implications, and overall impact of TBI among military combat veterans.

PMID- 20051902
TI  - Central arterial pulse wave augmentation is greater in girls than boys,
      independent of height.
AB  - OBJECTIVES: Central arterial pulse wave augmentation, quantified by the
      augmentation index (AIx), is a key marker of arterial health, an important
      contributor to cardiac afterload and is significantly greater in older women than
      men. We measured carotid AIx in 8-year-old children to examine the influences of
      sex, height and arterial stiffness on central arterial pulse wave augmentation
      METHODS: Four hundred and five children (age 8.0 +/- 0.1 years, 49% girls) had
      anthropometry, brachial systolic and diastolic blood pressure, heart rate and
      carotid artery pressure waveforms (by applanation tonometry), diastolic diameter
      and distensibility assessed. RESULTS: Carotid AIx was significantly higher in
      girls than boys (-11.7 +/- 8.1 versus -16.5 +/- 9.3%, respectively, P < 0.001).
      Boys and girls had similar height (129 +/- 6 versus 128 +/- 6 cm), systolic blood
      pressure (100 +/- 7 versus 101 +/- 7 mmHg), diastolic blood pressure (59 +/- 6
      versus 60 +/- 5 mmHg) and heart rate (80 +/- 10 versus 82 +/- 10 bpm). Carotid
      diastolic diameter was smaller in girls than boys (0.45 +/- 0.03 versus 0.47 +/-
      0.04 cm, P < 0.001). The sex difference in AIx remained significant after
      adjustment for height, heart rate, blood pressure, diastolic diameter and birth
      weight. The time to the onset of the reflected wave was shorter in girls (155 +/-
      19 versus 163 +/- 18 ms, P < 0.001). Girls had greater carotid artery
      distensibility (6.2 +/- 1.8 versus 5.8 +/- 1.5% per 10 mmHg, P = 0.016),
      suggesting lower regional carotid artery stiffness. CONCLUSION: Greater pulse
      wave augmentation in prepubertal girls results from earlier wave reflection and
      is independent of height, carotid artery diameter and stiffness. When combined
      with age-related changes in arterial compliance, this may contribute to adverse
      cardiovascular outcomes in older women.

PMID- 20051903
TI  - Microvascular dysfunction in healthy insulin-sensitive overweight individuals.
AB  - BACKGROUND: Obesity is associated with increased cardiovascular morbidity. The
      skin is a unique site allowing simple, noninvasive assessment of capillary
      density and endothelial function. In the present study, we measured skin
      capillary density and endothelial function in a group of normotensive
      overweight/obese nondiabetic individuals and healthy lean controls. METHODS AND
      RESULTS: We examined 120 relatively insulin-sensitive overweight individuals (BMI
      27.9 +/- 2.7 kg/m, mean +/- SD) with normal blood pressure and fasting plasma
      glucose and 130 lean (BMI 22.4 +/- 1.7 kg/m) controls. We used video microscopy
      to measure skin capillary density in the resting state and during venous
      occlusion. Laser Doppler flowmetry, combined with iontophoresis of acetylcholine
      (endothelial-dependent vasodilation) and following skin heating (endothelial
      independent dilation), was performed. Resting capillary density was negatively
      correlated with BMI (r = -0.130, P < 0.05). Resting capillary density (mean +/-
      SE) was lower, however nonsignificantly, in overweight as compared with the lean
      individuals (88.6 +/- 1.5 vs. 91.8 +/- 1.4, P = 0.117). Capillary recruitment,
      defined as the percentage increase in capillary density during venous congestion,
      was higher in overweight (9.5 +/- 1.0%) than in controls (5.4 +/- 0.9%, P =
      0.003), which remained significant after adjustment for age, sex, mean arterial
      pressure and fasting glucose. As a consequence, capillary density during venous
      occlusion was similar between the groups. Endothelial-dependent and independent
      cutaneous vasodilation was also similar between groups. No correlations were
      found between capillary density and plasma markers of adiposity, inflammation or
      endothelial dysfunction. CONCLUSION: BMI was inversely correlated with resting
      capillary density. This suggests a lower baseline tissue perfusion associated
      with higher vasomotor tone. Despite this, capillary recruitment was higher in
      overweight as compared with lean individuals, resulting in similar capillary
      density during venous congestion. Our results suggest that skin microcirculation
      abnormalities, in the absence of endothelial dysfunction, may be one of the
      earliest detectable alterations in vascular function in overweight individuals.

PMID- 20051904
TI  - Synergistic relationship between changes in the pulse wave velocity and changes
      in the heart rate in middle-aged Japanese adults: a prospective study.
AB  - OBJECTIVES: Temporal associations between rates of increases in pulse wave
      velocity (PWV), a marker of arterial stiffness, and heart rate (HR) indices
      (baseline HR and changes in HR) as well as inflammatory markers were examined.
      METHODS: In 1795 apparently healthy Japanese individuals (mean age 39 +/- 8 years
      old), brachial-ankle PWV (baPWV) and serum C-reactive protein (CRP) levels were
      measured at the baseline and at the end of a 5-6-year follow-up period. RESULTS:
      Heart rate at the baseline examination and changes in HR during the follow-up
      period were significantly associated with the corresponding changes in baPWV
      during the study period (nonstandardized co-efficient = 0.14, 95% confidential
      interval = 8.14 x 10-0.19, P < 0.01) even after the adjustment for atherogenic
      risk factors. When individuals were divided into four groups categorized by
      baseline HR (higher or lower than median HR) and increase/decrease in HR during
      the study period, serum CRP levels and atherogenic risk factors were
      significantly worse in the individuals with high baseline HR accompanied by
      increased HR during the study period. There was no significant relationship
      between the changes in the baPWV and the changes in the serum CRP levels. Even
      after the adjustment for confounding factors, changes in baPWV were significantly
      higher in this group than the other three groups (P < 0.01). CONCLUSIONS: The
      study results suggest a synergistic role of high baseline HR and increase in HR
      during the study period in accelerating age-associated increases in PWV.
      Inflammation might not be a major factor for this relationship.

PMID- 20051905
TI  - Morbidity and mortality on combination versus monotherapy: a posthoc analysis of
      the Systolic Hypertension in Europe trial.
AB  - BACKGROUND: The current literature supports the immediate use of combinations of
      antihypertensive drugs in terms of ease of use and adherence, but the key issue
      whether combination therapy is more effective than monotherapy in the prevention
      of cardiovascular complications remains unproven. METHODS: We analysed the double
      blind (median follow-up 2.0 years) and open follow-up (6.0 years) phases of the
      Systolic Hypertension in Europe trial. Patients were 60 years or more with an
      entry systolic/diastolic blood pressure (BP) of 160-219/less than 95 mmHg.
      Antihypertensive treatment started immediately after randomization in the active
      treatment group, but only after completion of the double-blind trial in control
      patients. Treatment consisted of nitrendipine (10-40 mg/day) with the possible
      addition of enalapril (5-20 mg/day). We adjusted our analyses for sex, age,
      history of cardiovascular complications, baseline systolic BP and previous
      antihypertensive treatment. RESULTS: During the double-blind trial, adding
      enalapril to nitrendipine (n = 515), compared with the equivalent combination of
      placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all
      cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032),
      with similar trends for stroke (-51%; P = 0.066) and cardiac events (-44%; P =
      0.075). Over the whole duration of follow-up, combination therapy (n = 871),
      compared with nitrendipine monotherapy (n = 1552), decreased systolic BP by 3.1
      mmHg and reduced total mortality (-32%; P = 0.023), with similar trends for all
      cardiovascular events (-23%; P = 0.081) and stroke (-42%; P = 0.054). CONCLUSION:
      Despite the limitations of a posthoc analysis, but congruent with the stronger BP
      reduction, our results suggest that combination therapy with nitrendipine plus
      enalapril might improve outcome over and beyond the benefits seen with
      nitrendipine monotherapy.

PMID- 20051906
TI  - Relations of central and brachial blood pressure to left ventricular hypertrophy
      and geometry: the Strong Heart Study.
AB  - OBJECTIVE: We previously demonstrated stronger relations of central vs. brachial
      blood pressure, particularly pulse pressure, to carotid artery hypertrophy and
      extent of atherosclerosis. Data regarding the relative impacts of central and
      brachial pressures on left ventricular hypertrophy and geometry are limited.
      METHODS: Echocardiography and radial applanation tonometry were performed in
      American Indian participants in the 4th Strong Heart Study examination. Left
      ventricular mass was calculated using an anatomically validated formula and
      adjusted for height. Brachial blood pressure was measured according to a
      standardized protocol. Central pressures were derived using a generalized
      transfer function. RESULTS: Of 2585 participants in the analysis, 60% were women,
      21% had diabetes and 33% were hypertensive; the mean age was 40 +/- 17 years. All
      blood pressure variables were significantly related to left ventricular absolute
      and relative wall thicknesses and left ventricular mass index (all P < 0.001),
      with considerable variation in correlation coefficients (r = 0.135-0.432).
      Central and brachial systolic pressures were uniformly more strongly related to
      left ventricular wall thicknesses, diastolic diameter and mass index than their
      respective pulse pressures (all P < 0.005 by z statistics). Left ventricular
      relative wall thickness and mass index were more strongly related to central than
      brachial pressures. CONCLUSION: Left ventricular hypertrophy is more strongly
      related to systolic pressure than to pulse pressure. Furthermore central
      pressures are more strongly related than brachial pressures to concentric left
      ventricular geometry. These data suggest that absolute (systolic) pressure is
      more important in stimulating left ventricular hypertrophy and remodeling,
      whereas pulsatile stress (pulse pressure) is more important in causing vascular
      hypertrophy and atherosclerosis.

PMID- 20051907
TI  - Desensitization of vascular response in vivo: contribution of genetic variation
      in the [alpha]2B-adrenergic receptor subtype.
AB  - OBJECTIVES: Vascular alpha2B-adrenergic receptors (alpha2B-ARs) mediate
      vasoconstriction and contribute to peripheral regulation of vascular tone. In
      vitro, a common 301-303 deletion in the alpha2B-AR gene, ADRA2B, results in loss
      of alpha2B-AR desensitization. We examined the hypothesis that ADRA2B del301-303
      or other common ADRA2B variants alter vascular desensitization in vivo. METHODS:
      We measured sensitivity to a highly selective alpha2-AR agonist, dexmedetomidine,
      (0.01-1000 ng/min) in the dorsal hand vein in 41 healthy individuals. To induce
      desensitization a dose of dexmedetomidine that resulted in submaximal
      constriction was infused for 180 min and dorsal hand vein responses measured.
      Desensitization was defined as the ratio between the area-under-the-effect curve
      for each individual's response and the hypothetical area-under-the-effect curve
      assuming that the initial response had been maintained for 180 min (ratio below 1
      reflecting desensitization). The relationship between six ADRA2B variants (one
      promoter, three coding, and two in the 3' untranslated region ) with an allele
      frequency of more than 5% and desensitization was determined. RESULTS: Forty-one
      individuals (22 men, 21 whites, age 18-45 years) were studied. The ADRA2B 301-303
      deletion allele (ins/del and del/del, n = 18) was associated with resistance to
      desensitization [1.01 (interquartile range 0.90-1.06)] as compared with ins/ins
      homozygous individuals (n = 23) [0.91 (interquartile range 0.73-0.99)], P =
      0.026. In addition, the -98 GG, 1182 CC, and 1776 CC genotypes were associated
      with significantly less desensitization than GC or CC, and CA or AA genotypes,
      respectively. CONCLUSION: Common ADRA2B variants contribute to the
      interindividual variability in vascular desensitization to an alpha2-AR agonist
      in vivo.

PMID- 20051908
TI  - The diagnosis and surgical management of juxtaglomerular cell tumor of the
      kidney.
AB  - Juxtaglomerular cell tumor (JCT) of the kidney is a rare benign renal neoplasm.
      Four cases of JCT of the kidney have been diagnosed and treated surgically in our
      hospital from January 2005 to August 2008. The clinical features, laboratory
      examination, imaging examination, pathological results and electron microscopy
      examination were analyzed, and a review of the literature was summarized. Three
      patients underwent open partial nephrectomy, and one patient underwent
      laparoscopic partial nephrectomy. Pathological examination confirmed the final
      diagnosis of JCT of the kidney. The blood pressure, potassium, renin and
      aldosterone remained within the normal range after surgery. JCT of the kidney
      should be kept in mind because they represent a surgically curable cause of
      secondary hypertension. Nephron-sparing surgery is recommended.

PMID- 20051909
TI  - Social integration, social contacts, and blood pressure dipping in African
      Americans and whites.
AB  - OBJECTIVE: Both the size and diversity of an individual's social network are
      strongly and prospectively linked with cardiovascular morbidity and mortality.
      Social relationships may influence cardiovascular outcomes, at least in part, via
      their impact on physiologic pathways influenced by stress, such as daytime blood
      pressure (BP) levels. However, scant research has examined whether social
      relationships influence key nocturnal pathways, such as nocturnal BP dipping.
      METHODS: The current study examined the degree to which social integration, as
      measured by participants' reported engagement in a range of different types of
      social relationships, and the frequency of daily social contacts influence the
      ratio of night/day mean arterial pressure (MAP) in a community sample of African
      American and white men and women (N = 224). In addition, we examined the degree
      to which observed associations persisted after statistical adjustment for factors
      known to covary with nocturnal BP, including objective measures of sleep,
      catecholamines, health behaviors, and comorbidities. RESULTS: In fully adjusted
      models, there was a significant association between both social integration and
      frequency of social contacts and the ratio of night/day MAP, indicating that
      socially isolated individuals were more likely to have blunted nocturnal BP
      dipping profiles. There was also a significant interaction between social contact
      frequency and ethnicity, suggesting that the benefits of social relationships
      were particularly evident in African-Americans. CONCLUSIONS: These findings
      contribute to our understanding of how social integration or conversely, social
      isolation, influences cardiovascular risk.

PMID- 20051910
TI  - Protection of retinal vasculature by losartan against apoptosis and vasculopathy
      in rats with spontaneous hypertension.
AB  - OBJECTIVES: Retinal blood vessels may develop vasculopathy and apoptosis in
      response to hypertension. The present study was aimed at testing the role of
      losartan, a specific antagonist of angiotensin II receptor type 1 receptor in
      regulation of vascular apoptosis in retinal vasculature with hypertension.
      METHODS: Losartan potassium was administered to spontaneously hypertensive rats
      (SHR). Blood pressure was measured in SHR as well as normotensive Wistar-Kyoto
      rats (WKY). Eye fundus was examined in living animals and then tissue specimens
      were collected for histochemistry by hematoxylin and eosin staining, terminal
      deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end
      labeling (TUNEL), immunohistochemistry and transmission electron microscopy.
      RESULTS: Losartan treatment for 4-8 weeks reduced blood pressure of SHR to the
      normal levels seen in WKY. The losartan-treated SHR showed marked improvement of
      retinal vascular morphology compared with untreated SHR. The retinal blood
      networks of the treated SHR developed lower degrees of vasculopathy and
      apoptosis. TUNEL and transmission electron microscopy also revealed that losartan
      exerted its protective effects not only on endothelial cells but on pericytes as
      well. The blood vessels of losartan-treated animals also showed decreased
      expression of bax with elevation of B-cell CLL/lymphoma 2. CONCLUSION: Treatment
      with losartan, a medicine that lowers blood pressure by blocking angiotensin II
      receptor type 1 receptor, can protect the retinal vasculature against
      hypertensive vascular injury by inhibiting apoptosis of vascular cells and by
      preventing hypertensive retinopathy.

PMID- 20051911
TI  - Antihypertensive medications and risk of community-acquired pneumonia.
AB  - OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitors
      and other antihypertensives are associated with risk of pneumonia. METHODS: We
      conducted a nested case-control study of incident pneumonia in a subcohort of
      hypertensive adults insured by several large commercial plans throughout the
      United States. Individuals with pneumonia were matched on age, sex, region, and
      subscriber status with up to 10 controls free of pneumonia at the time of case
      diagnosis. We examined use of beta-blockers, calcium channel blockers, ACE
      inhibitors (lipophilic and hydrophilic), angiotensin receptor blockers, and
      thiazides in the prior 3 and 12 months. RESULTS: A total of 7429 cases of
      pneumonia occurred among 305 958 hypertensive individuals. Risk of pneumonia was
      higher among users of beta-blockers [adjusted odds ratio (OR) 1.11; 95%
      confidence interval (CI) 1.03-1.19], calcium channel blockers (adjusted OR 1.09,
      95% CI 1.00-1.17), and lipophilic ACE inhibitors (adjusted OR 1.15, 95% CI 1.03
      1.28) in the preceding 3 months; risks were also higher for use in the preceding
      12 months. We observed lower risk with thiazide use in the preceding 3 months
      (adjusted OR 0.90, 95% CI 0.81-0.99) and hydrophilic ACE inhibitor use in the
      preceding year (adjusted OR 0.86, 95% CI 0.75-0.99). CONCLUSION: In this
      population of middle-aged Americans with hypertension, we observed a modestly
      higher risk of pneumonia with use of beta-blockers, calcium channel blockers, and
      lipophilic ACE inhibitors. These results are consistent with possible differences
      in noncardiovascular outcomes among users of antihypertensives and other commonly
      used cardiovascular drugs but require confirmation in other populations.

PMID- 20051912
TI  - The association between the -374T/A polymorphism of the receptor for advanced
      glycation endproducts gene and blood pressure and arterial stiffness is modified
      by glucose metabolism status: the Hoorn and CoDAM studies.
AB  - OBJECTIVES: Receptor for advanced glycation endproducts (RAGE)-ligand interaction
      may lead to vascular complications. Genetic variation in RAGE has been shown to
      alter expression, activity of RAGE or both. We, therefore, investigated whether
      RAGE single-nucleotide polymorphisms (SNPs) and haplotypes were associated with
      vascular disease. METHODS: Nine tag SNPs that cover the common RAGE gene
      variation were genotyped in 1291 individuals from two Dutch population-based
      cohort studies, aged 64.5 +/- 8.6 years, with normal glucose metabolism (44%),
      impaired glucose metabolism (23%) or type 2 diabetes mellitus (33%). We used
      multiple regression analyses to compare prevalent cardiovascular disease and
      markers of atherosclerosis, blood pressure and arterial stiffness across
      genotypes, and examine effect modification by glucose metabolism status. RESULTS:
      In unstratified analyses, no consistent associations between RAGE SNPs and
      prevalent cardiovascular disease and markers of atherosclerosis were found.
      However, the AA genotype of SNP rs1800624 (-374T/A) was consistently associated
      with lower SBP [-5.0 mmHg (95% confidence interval -10.4 to 0.3)] and DBP [-4.2 (
      7.2 to -1.3)], pulse pressure [-0.8 (-5.0 to 3.4)] as well as with less arterial
      stiffness [-0.56 SD (-1.04 to -0.09)] in individuals with normal glucose
      metabolism, but with higher SBP [6.2 (0.9-11.5)], DBP [2.1 (-0.7 to 5.0)] and
      pulse pressure [4.1 (-0.2 to 8.4)] in individuals with impaired glucose
      metabolism or type 2 diabetes mellitus (P for interaction <or=0.05 in all
      analyses). Similar results were found for a haplotype that includes the -374A
      allele. CONCLUSION: In individuals with normal glucose metabolism, the -374A
      allele of the RAGE gene is protectively associated with blood pressure and
      arterial stiffness, whereas in individuals with impaired glucose metabolism or
      type 2 diabetes mellitus, it is adversely associated with these variables.

PMID- 20051914
TI  - An unresectable malignant perivascular epithelioid cell tumor resistant to
      multiple combined chemotherapies: a unique case report.
AB  - SUMMARY: Malignant perivascular epithelioid cell tumor (PEComa) was a kind of
      rare disease with malignant behavior and poor prognosis. Nearly all PEComas show
      immunoactivity for HMB45. The treatment strategy for malignant PEComa is still of
      controversy, especially in advanced or unresectable disease. We reported a 14
      year-old patient of unresectable malignant PEComa, who was treated with multiple
      combined chemotherapies. The patient died of tumor 9 months after surgery,
      although 3 different combined chemotherapeutic regimens and antiangiogenic drug
      were used. Our case suggested that empirical chemotherapeutic regimens for soft
      tissue sarcomas might not be suitable for PEComa.

PMID- 20051913
TI  - Nitric oxide, oxidative stress and inflammation in pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a chronic and progressive disease
      characterized by a persistent elevation of pulmonary artery pressure accompanied
      by right ventricular hypertrophy (RVH). The current treatment for pulmonary
      hypertension is limited and only provides symptomatic relief due to unknown cause
      and pathogenesis of the disease. Both vasoconstriction and structural remodeling
      (enhanced proliferation of vascular smooth muscle cell) of the pulmonary arteries
      contribute to the progressive course of PAH, irrespective of different underlying
      causes. The exact molecular mechanism of PAH, however, is not fully understood.
      The purpose of this review is to provide recent advances in the mechanistic
      investigation of PAH. Specifically, this review focuses on nitric oxide,
      oxidative stress and inflammation and how these factors contribute to the
      development and progression of PAH. This review also discusses recent and
      potential therapeutic advancements for the treatment of PAH.

PMID- 20051915
TI  - Spontaneous resolution of angular deformity of the distal femur in focal
      fibrocartilaginous dysplasia: a case report.
AB  - Focal fibrocartilaginous dysplasia (FFCD) is a rare cause of angular deformities
      around the knee in children. The FFCD lesion most commonly affects the proximal
      tibia and less commonly the distal femur. We report a case of distal femoral
      varus deformity secondary to FFCD. Spontaneous resolution of the deformity
      occurred during a 7-year period. Previous reported femoral cases showed
      progressive deformity and required treatment with soft-tissue releases with or
      without osteotomy. This is the first reported femoral case of spontaneous
      resolution of angular deformity secondary to FFCD. We recommend a trial of
      observation for distal femoral lesions before surgical intervention.

PMID- 20051916
TI  - Etiology of cervical myelopathy induced by ossification of the posterior
      longitudinal ligament: determining the responsible level of OPLL myelopathy by
      correlating static compression and dynamic factors.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To determine the responsible level
      of cervical myelopathy induced by ossification of the posterior longitudinal
      ligament (OPLL). This was achieved by correlating the intervertebral range of
      motion (ROM) as the dynamic factor with the space available for spinal cord (SAC)
      as the static compression factor. SUMMARY OF BACKGROUND DATA: The association
      between spinal canal stenosis and the occurrence of the myelopathy has previously
      been reported for OPLL patients, but not the detailed relationship between SAC,
      ROM, and myelopathy. METHODS: We investigated OPLL type, SAC, and ROM in relation
      to the responsible level of cervical OPLL myelopathy in 27 cases. SAC and ROM
      were measured at each vertebral and intervertebral levels. The responsible level
      was diagnosed using spinal cord-evoked potentials and classified as group A,
      whereas the nonresponsible level was classified as group B. RESULTS: Spinal cord
      evoked potentials revealed 21 cases with a single responsible level and 6 cases
      with 2 responsible levels. The mean ROM of group A (8.9 degrees) was
      significantly higher (P<0.01) than that of group B (5.7 degrees). The mean SAC of
      group A (8.2 mm) was significantly lower (P<0.01) than that of group B (12.4 mm).
      Using discriminate analysis, significant differences for both SAC and ROM were
      observed between groups A and B [Box's M test: chi=3.31 <chi3 (0.05)]. The
      discriminate formula for the borderline of symptomatic spinal compression can be
      described as: Z=-0.21ROM+0.47SAC-2.76. CONCLUSIONS: Cervical OPLL myelopathy is
      induced by static factors, dynamic factors, or a combination of both. The
      discriminate formula for symptomatic cervical OPLL myelopathy contains both ROM
      and SAC.

PMID- 20051917
TI  - Lower incidence of dysphagia with cervical arthroplasty compared with ACDF in a
      prospective randomized clinical trial.
AB  - STUDY DESIGN: The current study of 251 consecutive 1-level anterior cervical
      reconstructions was undertaken to compare the incidence of dysphagia between
      cervical disk replacement and conventional anterior cervical fusion and
      instrumentation. OBJECTIVES: This is a report of 251 patients from 5
      investigational centers in the Food and drug Administration's prospective,
      randomized porous-coated motion (PCM) trial using a validated dysphagia outcomes
      instrument. The dysphagia data for both PCM and anterior cervical diskectomy and
      fusion (ACDF) patients were reviewed from 5 centers to (1) compare the severity
      of dysphagia, (2) compare the postoperative incidence of dysphagia, and (3) to
      compare the resolution of perioperative dysphagia. SUMMARY OF BACKGROUND DATA:
      Dysphagia and dysphonia after anterior surgical approaches to the cervical spine
      have been previously reported. The current prospective, randomized investigation
      quantifies clinical dysphagia based on 3 criteria-severity, incidence, and
      resolution-in a time-course evaluation. METHODS: Patients between 18 and 65 years
      with 1-level symptomatic cervical radiculopathy and/or myelopathy for progressive
      neurologic symptoms, were randomized to undergo anterior decompression and PCM
      arthroplasty (N=151) or ACDF (control) (N=100). Patients self-reported dysphagia
      severity using the Bazaz scale preoperatively and at follow-up. The Bazaz scale
      has 4 classes of severity based upon the problems with swallowing that the
      patient has with both liquids and solids. RESULTS: The Bazaz results demonstrate
      that although both the PCM and ACDF groups exhibited an initial postoperative
      problem with swallowing, the PCM group continued to improve with increasing time
      after implantation, whereas the ACDF only improved minimally. The PCM treatments
      indicated significantly lower incidence of dysphagia at 3 and 12 months
      postoperatively compared with ACDF controls (P<0.05). An increase in dysphagia
      severity at either the 6-week or 3-month follow-up visit was reported in 35 (42%)
      PCM and 29 (64%) ACDF subjects. Long-term resolution of these symptoms was noted
      in 74% (26/35) of the PCM subjects as compared with 41.4% (12/29) of the ACDF
      subjects (P=0.015). CONCLUSIONS: In a prospective randomized clinical study the
      incidence of postoperative dysphagia and the long-term resolution of the
      dysphagia was greatly improved in the PCM group compared with the instrumented
      ACDF control group.

PMID- 20051918
TI  - Teriparatide may accelerate healing in delayed unions of type III odontoid
      fractures: a report of 3 cases.
AB  - STUDY DESIGN: Case Report. OBJECTIVE: To report on the treatment of 3 cases of
      painful delayed unions of type III odontoid fractures with teriparatide. SUMMARY
      OF BACKGROUND DATA: Fractures of the C2 vertebra, also known as odontoid
      fractures, are an important subset of cervical spine fractures. Type III odontoid
      fractures pass through predominately cancellous bone of C2. Generally accepted
      treatment is external immobilization with either a rigid collar or a halo vest
      for 8 to 12 weeks. We report 3 patients who, despite external immobilization,
      developed painful delayed unions of type III odontoid fractures. Teriparatide is
      a novel anabolic drug therapy for osteoporosis. It has been shown to stimulate
      osteoblasts, enhance bone connectivity, increase endosteal cortical thickness,
      and improve bone mineral content. The drug is given through subcutaneous
      injection of 20 microg/d for between 6 weeks and 2 years. We treated these 3
      patients with teriparatide. Each was informed that details of their case would be
      submitted for publication. METHODS: Retrospective case analysis. RESULTS: All 3
      patients experienced both rapid clinical improvement and computed tomography
      evidence of fracture union. CONCLUSION: These 3 cases represent relatively
      uncommon clinical scenarios in which type III odontoid fractures in osteoporotic
      women failed to unite with external immobilization over several months. The
      patients presented for follow-up with substantial, activity-limiting neck pain.
      All 3 were begun on teriparatide doses therapeutic for osteoporosis, and all 3
      experienced both remarkable resolution of chronic neck pain and computed
      tomography-confirmed union of the fractures.

PMID- 20051919
TI  - Surgical outcome of 2-stage (posterior and anterior) surgical treatment using
      spinal instrumentation for tuberculous spondylitis.
AB  - STUDY DESIGN: A prospective study on the clinical outcomes in patients with
      tuberculous spondylitis treated by a 2-stage operation (posterior and anterior)
      using posterior spinal instrumentation. OBJECTIVE: To evaluate the clinical
      outcomes of the 2-stage surgical treatment (first stage: placement of posterior
      instrumentation and second stage: anterior debridement and bone grafting) for
      tuberculous spondylitis. SUMMARY OF BACKGROUND DATA: There have been few reports
      describing the effects of 2-stage surgical treatment for tuberculous spondylitis.
      METHODS: Ten patients (5 men and 5 women) with tuberculous spondylitis were
      treated by 2-stage operations. Age at the initial operation was 64.6+/-14.8 years
      (average+/-SD) (range: 47 to 83 y). The clinical outcomes were evaluated before
      and after the surgery in terms of hematologic examination, pain level, and
      neurologic status. Bone fusion and changes in sagittal alignment were examined
      radiographically. RESULTS: All patients showed suppression of infection, bony
      fusion, relief of pain, and recovery of neurologic function. No significant
      changes were observed in kyphosis angle at the final follow-up. There were no
      incidences of severe complications or recurrence. CONCLUSIONS: Our results showed
      that posterior and anterior 2-stage surgical treatment for tuberculous
      spondylitis is a viable surgical option for cases in which conservative treatment
      has failed. However, the changes in sagittal alignment showed that this strategy
      provides limited kyphosis correction.

PMID- 20051920
TI  - Pedicle screw augmentation with polyethylene tape: a biomechanical study in the
      osteoporotic thoracolumbar spine.
AB  - STUDY DESIGN: Biomechanical study using human thoracolumbar spines. OBJECTIVE: To
      assess the strength of fixation of pedicle screws augmented with Nesplon tape
      applied sublaminar or applied subpars. SUMMARY OF BACKGROUND DATA: There are no
      reports on the biomechanical assessment of Nesplon tape used for pedicle screw
      augmentation. METHODS: Experiment 1: pedicle screws were inserted into bilateral
      pedicles as follows: (1) pedicle screw alone connected to a rod (PS alone), (2)
      pedicle screw augmented with Nesplon tape applied sublaminar, connected to a rod
      [pedicle screw applied sublaminar (PSSL)], and (3) pedicle screw augmented with
      tape applied subpars, connected to a rod [pedicle screw applied subpars (PSSP)].
      The rods were pulled and pushed until the pedicle screw was loose. Experiment 2:
      6 thoracolumbar spines were biomechanically tested as follows: axial compression,
      flexion, extension, left and right lateral bending, and left and right axial
      rotation. This sequence was applied to: (1) the intact spine; (2) the spine made
      unstable; (3) the spine fixed by pedicle screws and rods (PS alone); (4) the same
      as 3, but with the pedicle screws augmented using Nesplon tape applied sublaminar
      (PSSL); and (5) the same as 3, but with pedicle screws augmented using tape
      applied subpars (PSSP). From the load-deformation curves, stiffness values were
      calculated. RESULTS: Experiment 1: the pedicle screws augmented by sublaminar or
      subpars tape (PSSL or PSSP) showed significantly greater fixation strength
      compared with those pedicles that were not augmented by tape (PS alone).
      Experiment 2: a pedicle screw/rod construct augmented by tape provided a stiffer
      construct than the same construct without augmentation. CONCLUSIONS: Pedicle
      screws that are inserted into the osteoporotic thoracolumbar spine and augmented
      by Nesplon tape applied sublaminar or subpars provide firmer fixation of the
      screws and a stiffer pedicle screw/rod construct than the same construct without
      augmentation by tape.

PMID- 20051921
TI  - Quality of spinal motion with cervical disk arthroplasty: computer-aided
      radiographic analysis.
AB  - STUDY DESIGN: Kinematic study of a single site in an investigational device
      exemption trial. OBJECTIVE: Evaluate the center of rotation (COR) after Bryan
      cervical arthroplasty and compare adjacent segment motion after cervical disk
      arthroplasty and fusion using validated radiographic analysis. SUMMARY OF
      BACKGROUND DATA: The goal of cervical arthroplasty is to reestablish spinal
      kinematics after anterior decompression. Excellent maintenance of range of motion
      has been reported for a variety of the prostheses; however, the manner the
      prostheses perform this task is different. A parameter that may be as important
      as range of motion is restoring the quality of motion. One of the important
      components is the COR that is easily studied biomechanically but has not been
      reported from in vivo studies. Furthermore, the effects on the quality of motion
      at adjacent levels have not been studied. The purpose of this study is to
      determine the quality of motion after Bryan cervical disk arthroplasty at the
      target level and the adjacent segments. METHODS: The first 48 patients diagnosed
      with single level cervical disk degenerative disease and associated myelopathy or
      radiculopathy from a single institution enrolled in the Bryan disk
      investigational device exemption trial were selected for inclusion. Twenty-two
      investigational patients and 26 anterior cervical discectomy and fusion controls
      were evaluated radiographically preoperatively and 3, 6, 12, and 24 months
      postoperatively. These results were analyzed using Quantitative Motion Analysis
      software manufactured by Medical Metrics Inc. Kinematic parameters included
      translation, sagittal rotation, anterior/posterior disk height, and the
      calculation of the COR both in the sagittal and coronal planes. RESULTS: At the
      arthroplasty level, the COR shifted more posterior (0.3 mm, 1% end plate width)
      and cephalad (4.9 mm, 20% end plate width) compared with the preoperative
      position, however, this change was not statistically significant (P=0.06). The
      variability of the COR, however, was less after arthroplasty compared with
      preoperative values. There was no significant difference in the short term
      between the adjacent levels after fusion compared with the prosthesis. At later
      time points (12 and 24 mo), however, the COR was significantly posterior at the
      level above arthroplasty compared with fusion (P<0.01). COR X was not
      significantly (P>0.3) different below fusions compared with arthroplasty.
      Sagittal rotation significantly increased at the level above for both the fusion
      and prosthesis groups. A trend was noted for increased translation (2.5% end
      plate width) at the level above a fusion compared with the Bryan disk at 24
      months postoperatively, but this did not reach statistical significance.
      CONCLUSIONS: Sagittal rotation increases above the level of the arthroplasty and
      fusion. In the long term, the arthroplasty group had a more posterior COR at the
      level above, compared with the level above a fusion. Translation at the level
      above a fusion was slightly increased but not statistically compared with the
      level above the arthroplasty with similar amounts of sagittal rotation
      (flexion/extension). Although not reaching statistical significance, the COR
      seemed to shift more posterior and cephalad at the arthroplasty level with less
      variability compared with the preoperative position.

PMID- 20051922
TI  - Microendoscopic anterior approach for irreducible atlantoaxial dislocation:
      surgical techniques and preliminary results.
AB  - STUDY DESIGN: Surgical techniques and preliminary results. OBJECTIVE: To describe
      and evaluate the safety and efficacy of a new minimal invasive technique for the
      irreducible atlantoaxial dislocation (IADD). SUMMARY OF BACKGROUND DATA:
      Endoscope has been widely used in minimal invasive spinal surgery. However, there
      are no clinical reports regarding anterior approach for IADD in the literature.
      METHODS: Ten consecutive patients with IADD were treated by anterior release with
      microendoscopic aide and subsequently reduction, anterior transarticular screw
      fixation and morselized autologous bone grafts. There were 3 cases of odontoid
      dysplasia, 4, chronic odontoid fracture, 1, odontoid absence, 1 fasilar
      impression, and 1 malunion of odontoid fracture. According to Symon and
      Lavender's classification of disability, 6 cases were moderate disability, 3
      severe nonbedbound, and 1 severe bedridden. The procedure was performed by the
      same surgeon (Yong-Long Chi). RESULTS: The new technique was performed
      successfully in all cases. All the patients underwent transarticular screw
      fixation and anterior morselized autograft fusion. The average operation time was
      120 min (range, 90 to 150 min) and the mean estimated blood loss was 150 mL
      (range, 100 to 250 mL). Postoperative radiographs demonstrated that 9 cases
      restored anatomic position and 1 had partial reduction. According to the
      postoperative computed tomography all the screws were appropriately placed.
      Follow-up after surgery, longest is 16 months and minimal 8 months with a mean of
      12 months, neurologic status was improved in all patients. There was no loss of
      fixation and solid fusion was achieved in all cases. CONCLUSIONS: Surgical
      technique of microendoscopic anterior release, reduction, fixation, and fusion is
      safe and reliable minimally invasive for treating IADD.

PMID- 20051923
TI  - A Comparison of fixed-hole and slotted-hole dynamic plates for anterior cervical
      discectomy and fusion.
AB  - STUDY DESIGN: A retrospective review of clinical data at 1 institution was
      performed. OBJECTIVES: To compare the clinical and radiologic outcomes between
      fixed-hole and slotted-hole dynamic cervical plates. SUMMARY OF BACKGROUND DATA:
      Anterior cervical plating is commonly used to increase stability and promote
      spinal fusion. Two techniques, fixed-hole dynamic plating that uses variable
      angled screws and slotted-hole dynamic plating that permits sliding, are viable
      options, but there have been no clinical studies comparing their effectiveness.
      METHODS: Fifty-six patients at 1 institution having anterior cervical discectomy
      and fusion for degenerative disease over a 5-year period were entered into this
      study. Surgeries were performed with 1 of the dynamic plates for 1 to 3 levels.
      For the slotted-hole dynamic plate group, a slotted-hole plate was used (ABC,
      Aesculap, Tuttlingen, Germany or C-tek, Biomet, Parssipany, NJ) and for the fixed
      hole dynamic plated group, a variable angled screw was used (C-tek, Biomet,
      Parssipany, NJ). Radiographic measurements included were graft subsidence,
      lordotic angle change from each end plate of fusion construct, and implant
      translation from end plates after a minimum of 12 months follow-up. Fusion state
      and clinical outcome using Odom's criteria were also evaluated. RESULTS:
      Demographics were not different among patient populations. The average age of the
      patients was 51.0 years (range: 27 to 77 y). Mean follow-up period was 20.6
      months (range: 12 to 41 mo). Slotted-hole dynamic plates were used for 29
      patients (ABC plate, 17; C-tek plate, 12) and fixed-hole dynamic plates for 27
      patients. Clinical outcomes and pseudoarthrosis rates were similar for both types
      of plates. Radiographic measurements showed a statistically significant increased
      incidence of graft subsidence and implant translation with the slotted-hole
      dynamic plates. Loss of lordosis was also greater in the slotted-hole dynamic
      plated group, although the difference was not statistically significant.
      CONCLUSIONS: The use of a fixed-hole dynamic plate is more favorable in regards
      to graft subsidence and implant translation in the follow-up period, although
      clinical outcome and fusion rates are similar in patients with either the fixed
      hole or slotted-hole dynamic plates.

PMID- 20051924
TI  - Normal functional range of motion of the cervical spine during 15 activities of
      daily living.
AB  - STUDY DESIGN: Prospective clinical study. OBJECTIVE: The purpose of this
      investigation was to quantify normal cervical range of motion (ROM) and compare
      these results to those used to perform 15 simulated activities of daily living
      (ADLs) in asymptomatic subjects. SUMMARY OF BACKGROUND DATA: Previous studies
      looking at cervical ROM during ADLs have been limited and used measuring devices
      that do not record continuous motion. The purpose of this investigation was to
      quantify normal cervical ROM and compare these results with those used to perform
      15 simulated ADLs in asymptomatic subjects. METHODS: A noninvasive
      electrogoniometer and torsiometer were used to measure the ROM of the cervical
      spine. The accuracy and reliability of the devices were confirmed by comparing
      the ROM values acquired from dynamic flexion/extension and lateral bending
      radiographs to those provided by the device, which was activated while the
      radiographs were obtained. Intraobserver reliability was established by
      calculating the intraclass correlation coefficient for repeated measurements on
      the same subjects by 1 investigator on consecutive days. These tools were
      employed in a clinical laboratory setting to evaluate the full active ROM of the
      cervical spines (ie, flexion/extension, lateral bending, and axial rotation) of
      60 asymptomatic subjects (30 females and 30 males; age, 20 to 75 y) as well as to
      assess the functional ROM required to complete 15 simulated ADLs. RESULTS: When
      compared with radiographic measurements, the electrogoniometer was found to be
      accurate within 2.3+/-2.2 degrees (mean+/-SD) and the intraobserver reliabilities
      for measuring the full active and functional ROM were both excellent (intraclass
      correlation coefficient of 0.96 and 0.92, respectively). The absolute ROM and
      percentage of full active cervical spinal ROM used during the 15 ADLs was 13 to
      32 degrees and 15% to 32% (median, 20 degrees/19%) for flexion/extension, 9 to 21
      degrees and 11% to 27% (14 degrees/18%) for lateral bending, and 13 to 57 degrees
      and 12% to 92% (18 degrees/19%) for rotation. Backing up a car required the most
      ROM of all the ADLs, involving 32% of sagittal, 26% of lateral, and 92% of
      rotational motion. In general, personal hygiene ADLs such as washing hands and
      hair, shaving, and applying make-up entailed a significantly greater ROM relative
      to locomotive ADLs including walking and traveling up and down a set of stairs
      (P<0.0001); in addition, compared with climbing up these steps, significantly
      more sagittal and rotational motion was used when descending stairs (P=0.003 and
      P=0.016, respectively). When picking up an object from the ground, a squatting
      technique required a lower percentage of lateral and rotational ROM than bending
      at the waist (P=0.002 and P<0.0001). CONCLUSIONS: By quantifying the amounts of
      cervical motion required to execute a series of simulated ADLs, this study
      indicates that most individuals use a relatively small percentage of their full
      active ROM when performing such activities. These findings provide baseline data
      which may allow clinicians to accurately assess preoperative impairment and
      postsurgical outcomes.

PMID- 20051925
TI  - Clinical outcomes after microendoscopic discectomy for recurrent lumbar disc
      herniation.
AB  - STUDY DESIGN: Retrospective review of consecutive case series. OBJECTIVE: To
      assess the safety and efficacy of the microendoscopic approach for treatment of
      recurrent lumbar disc herniation. SUMMARY OF BACKGROUND DATA: The standard
      surgical approach for the treatment of recurrent disc herniation uses an open
      technique with a wide exposure. Many would consider a minimally invasive approach
      such as microendoscopic discectomy (MED) to be contraindicated in the setting of
      recurrent disc herniation. METHODS: Sixteen consecutive patients with recurrent
      lumbar disc herniation who failed conservative management underwent MED. Before
      surgery and at follow-up, patients completed the Oswestry Disability Index, SF
      36, and assessment of leg pain using the Visual Analog Scale. Outcome was also
      assessed using modified McNab criteria. RESULTS: No case required conversion to
      an open procedure. Mean operative time was 108 minutes, and mean estimated blood
      loss was 32 mL. The only surgical complications were 2 durotomies that were
      treated with dural sealant without sequelae. Mean hospital stay was 23 hours, and
      mean follow-up was 14.7 months. Approximately 80% of patients had good or
      excellent outcomes based on modified McNab criteria. The remaining 3 patients had
      fair outcomes, and no patient had a poor outcome. All standardized measures
      improved significantly, including mean Visual Analog Scale for leg pain (8.2 to
      2.2, P<0.001), mean Oswestry Disability Index (59.3 to 26.7, P<0.001), SF-36
      Physical Component Summary score (28.3 to 42.4, P<0.001), and SF-36 Mental
      Component Summary score (38.2 to 48.3, P<0.001). As of last follow-up no patient
      has showed recurrence of herniation or evidence of delayed instability.
      CONCLUSIONS: MED is a safe and effective surgical approach for the treatment of
      recurrent lumbar disc herniation. Standardized measures of outcome show that MED
      for recurrent herniation produces improvement in pain, disability, and functional
      health that is at least comparable with outcomes reported for conventional open
      microdiscectomy.

PMID- 20051926
TI  - GAD67-GFP knock-in mice have normal sleep-wake patterns and sleep homeostasis.
AB  - Gamma-aminobutyric acid (GABA) ergic neurons are important for controlling sleep
      and wakefulness but are difficult to identify, limiting their study. Knock-in
      mice with GABAergic neurons labeled by expression of green fluorescent protein
      (GFP) under control of the glutamate decarboxylase 67 (GAD67) promoter are now
      extensively used in neuroscience. However, it is unknown whether these mice have
      a normal sleep phenotype. Compared with wild-type control mice, GAD67-GFP knock
      in mice had the same amount of non-rapid eye movement (NREM) sleep and rapid-eye
      movement (REM) sleep, a similar diurnal distribution of sleep, no NREM or REM
      sleep differences in electroencephalogram power, and normal sleep rebound
      following 6-h sleep deprivation. Our results suggest GAD67-GFP knock-in mice are
      an excellent tool for study of GABAergic neurons involved in sleep-wake
      regulation.

PMID- 20051927
TI  - F-18 FDG-PET in children: do we have enough counts?
AB  - PURPOSE: The aim of the study was to find out whether in [F]fluoro-2-deoxy-D
      glucose positron emission tomography (F-18 FDG-PET) performed in children in our
      department, the number of counts were sufficiently high to guarantee optimal
      image quality. METHODS: Phantom data with negative and positive lesions were
      acquired with an increasing count density and the relationship between image
      quality and counts per voxel was analyzed. On PET images obtained in 28 children
      aged 4-17 years and using a standard administered activity of 6.5 MBq/kg with a
      minimum of 74 MBq, the maximum counts per voxel in 10 regions of interest were
      noted and compared with those obtained on phantoms. RESULTS: Phantom data showed
      clearly the effect of higher count on image quality. Moreover, when high counts
      were available, reconstruction could be done using 2 mm voxel size, which
      improved the quality of the images further. In children, the counts per voxel in
      all the regions of interest, with the exception of the brain, were at a level of
      suboptimal image quality. CONCLUSION: By following the official guidelines, the
      counts per voxel observed in children with our gadolinium oxyorthosilicate-PET
      system were lower than the minimal required to produce optimal quality images.
      More efficient PET systems or higher F-18 FDG dose or increasing the acquisition
      time or combination of these factors are needed to improve the image quality and
      lesion detection.

PMID- 20051928
TI  - Viral coinfections in children with invasive pneumococcal disease.
AB  - BACKGROUND: Respiratory viruses contribute to the seasonal pattern of invasive
      pneumococcal disease (IPD), but the impact of viral coinfections on the clinical
      characteristics and outcomes of patients with IPD have not been well defined.
      OBJECTIVE: This study was designed to describe and compare the clinical
      presentations and outcomes of patients with IPD with or without viral
      coinfections. DESIGN/METHODS: Retrospective analyses of records of all children
      treated at Children's Medical Center Dallas (CMCD) for IPD from July 2005 to June
      2008. Viral studies included viral direct fluorescent antibody staining and
      culture. For comparisons, patients were classified in 3 groups: with positive,
      negative, and no viral studies performed. RESULTS: A total of 129 patients were
      admitted to CMCD with IPD during the 3 year study; 57% were male. Ages ranged
      from 2 months to 18 years (median 25 months) and 48% were <2 years. Viral studies
      were performed in 82 (63%) patients, and 28 (34%) had positive results. The most
      common viruses isolated were influenza (7, 25%), rhinoviruses (6, 21%),
      adenoviruses (6, 21%), and RSV (5, 18%). Peaks of positive viral studies occurred
      in February and November which coincided with the peak numbers of patients
      admitted with IPD. Of 6 with adenovirus coinfection, 5 were admitted to Pediatric
      Intensive Care Unit (PICU). The most common pneumococcal serotypes were 19A (41,
      32.5%), 7F (14, 11%), and 23A (13, 10.3%). Pneumonia (42%), bacteremia (22%), and
      meningitis (17%) were the most common clinical syndromes. There were no
      differences in duration of fever before admission, maximum temperatures during
      hospitalization and white blood cell counts, duration of fever and
      hospitalization between patients with positive and negative viral studies, but
      there was a trend for patient with positive viral studies to be admitted to PICU
      more frequently and to have longer PICU stay. Three of the 6 patients who died
      had documented viral coinfections (2 adenovirus, 1 parainfluenza 3), and all 3
      had no underlying conditions. The other 3 patients who died had no viral studies
      performed. Duration of treatment ranged from 1 to -210 days (median 14), with no
      differences among the groups. CONCLUSIONS: Viral coinfections were common in
      children with IPD. Future prospective studies should include new PCR assays to
      characterize better the impact of viral coinfections in the occurrence and
      outcome of IPD.

PMID- 20051929
TI  - HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and
      lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms.
AB  - OBJECTIVE: OATP1B1 and OATP1B3 are major hepatic drug transporters whilst OATP1A2
      is mainly located in the brain but is also located in liver and several other
      organs. These transporters affect the distribution and clearance of many
      endobiotics and xenobiotics and have been reported to have functional single
      nucleotide polymorphisms (SNPs). We have assessed the substrate specificities of
      these transporters for a panel of antiretrovirals and investigated the effects of
      SNPs within these transporters on the pharmacokinetics of lopinavir. METHODS:
      SLCO1A2, SLCO1B1 and SLCO1B3 were cloned, verified and used to generate cRNA for
      use in the Xenopuslaevis oocyte transport system. Using the oocyte system,
      antiretrovirals were tested for their substrate specificities. Plasma samples
      (n=349) from the Liverpool therapeutic drug monitoring registry were genotyped
      for SNPs in SLCO1A2, SLCO1B1 and SLCO1B3 and associations between SNPs and
      lopinavir plasma concentrations were analysed. RESULT: Antiretroviral protease
      inhibitors, but not non-nucleoside reverse transcriptase inhibitors, are
      substrates for OATP1A2, OATP1B1 and OATP1B3. Furthermore, ritonavir was not an
      inhibitor of OATP1B1. The 521T>C polymorphism in SLCO1B1 was significantly
      associated with higher lopinavir plasma concentrations. No associations were
      observed with functional variants of SLCO1A2 and SLCO1B3. CONCLUSION: These data
      add to our understanding of the factors that contribute to variability in plasma
      concentrations of protease inhibitors. Further studies are now required to
      confirm the association of SLCO1B1 521T>C with lopinavir plasma concentrations
      and to assess the influence of other polymorphisms in the SLCO family.

PMID- 20051930
TI  - Sexual partner concurrency and sexual risk among gay, lesbian, bisexual, and
      transgender American Indian/Alaska natives.
AB  - BACKGROUND: American Indian and Alaska Natives suffer pervasive health
      disparities, including disproportionately high rates of HIV. Sexual network
      dynamics, including concurrency and sexual mixing patterns, are key determinants
      of HIV disparities. METHODS: We analyzed data from the first national study of
      gay, lesbian, bisexual, and transgender American Indian and Alaska Natives to
      examine the prevalence of concurrency, sex and race of partners, and level of
      risk across different partnership patterns. Egocentric network data were analyzed
      at the level of the respondents, who were grouped according to the sex of their
      last 3 partners. RESULTS: Overall rates of HIV and concurrency were high in this
      population. HIV prevalence (34%) and cumulative prevalence of concurrency (55%)
      were highest among men who had sex with only men, while women who had sex with
      only women reported lower concurrency and HIV. Women who had sex with women and
      men also had high HIV prevalence (15%) and reported slightly higher concurrency
      risk and low condom use, making them effective bridge populations. CONCLUSIONS:
      The uniformly high rates of Native partner selection creates the potential for
      amplification of disease spread within this small community, while the high rates
      of selecting partners of other races creates the potential for bridging to other
      groups in the transmission network. These findings provide some of the first
      insights into sexual networks and concurrency among Native gay, lesbian,
      bisexual, and transgender populations and suggest that both men and women deserve
      attention in HIV prevention efforts at individual, dyadic and population levels.

PMID- 20051931
TI  - Pelvic inflammatory disease among privately insured women, United States, 2001
      2005.
AB  - BACKGROUND: We explored the utility of using insurance claims data for
      surveillance of pelvic inflammatory disease (PID). PID rates are an important
      indicator of population level trends in reproductive morbidity; however, data
      available to monitor PID trends are limited. National survey data are currently
      used to estimate PID rates in the United States, but a declining number of cases
      threaten their future usefulness. METHODS: We performed a retrospective analysis
      of PID diagnosis rates using administrative claims data from 2001 to 2005.
      Diagnostic codes were used to identify women aged 15 to 44 in the study
      population that were diagnosed with acute PID as inpatients, in emergency
      departments, and in outpatient ambulatory settings. RESULTS: Rates of PID
      diagnoses among privately insured women declined significantly from 2001 to 2005
      among all age groups examined and within all geographic regions. Annual PID
      diagnosis rates decreased from 317.0 to 236.0 per 100,000 enrollees, representing
      a 25.5% decline over the study period. The highest rates of PID were among 25- to
      29-year-olds (352.8 per 100,000 in 2005) and among those residing in the South
      (314.3 per 100,000 in 2005). Most women (70.1%) received PID care through
      physician offices and other outpatient facilities; of these women, approximately
      40% were treated by an obstetrician/gynecologist. CONCLUSIONS: The decline in PID
      diagnoses corresponds with previous reports from national surveys. Claims data
      offer a much needed new data source that will allow for continued monitoring of
      PID among a broad population in both inpatient and outpatient clinical settings.

PMID- 20051933
TI  - Bridging the childhood cancer mortality gap between economically developed and
      low-income countries.

PMID- 20051932
TI  - Correlates of cervical Mycoplasma genitalium and risk of preterm birth among
      Peruvian women.
AB  - BACKGROUND: Mycoplasma genitalium is associated with cervicitis and pelvic
      inflammatory disease in nonpregnant women. We investigated associations between
      cervical M genitalium, demographic and behavioral risk factors for sexually
      transmitted infection and preterm birth among low-income Peruvian women. METHODS:
      This case-control study, conducted at the Instituto Nacional Materno Perinatal,
      Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and
      667 controls who delivered at >or=37 weeks. Within 48 hours after delivery,
      subjects underwent interviews, medical record review, and collection of
      cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria
      gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by
      culture. Odds ratios and 95% confidence intervals were calculated for
      associations between M. genitalium, other genital infections and risk factors,
      and preterm birth. Multivariable logistic regression was used to adjust for
      potential confounders. RESULTS: Cervical M. genitalium was detected in 3% of
      subjects and was significantly associated with C. trachomatis infection (P <
      0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence
      interval: 1.2-5.0, P = 0.014), and marginally associated with T. vaginalis (P =
      0.05). M. genitalium detection was also associated with younger maternal age (P =
      0.003) but not with other risk factors for preterm birth. The association between
      cervical M. genitalium detection and preterm birth remained significant after
      adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis.
      CONCLUSIONS: Cervical M. genitalium detection was independently associated with
      younger maternal age and preterm birth, suggesting that this organism may be an
      infectious correlate of spontaneous preterm birth.

PMID- 20051934
TI  - A breast-fed newborn with megaloblastic anemia-treated with the vitamin B12
      supplementation of the mother.
AB  - Pregnant women with low B12 levels are unable to provide the necessary amount of
      this vitamin to their fetuses. The mothers are usually not anemic, and failure to
      thrive and neurologic deficits are more common in their infants than in
      megaloblastic anemia. We report the case of a newborn that was born to a
      vegetarian mother and presented with the symptoms of megaloblastic anemia at
      birth; we also discuss vitamin B12 metabolism during pregnancy and lactation. An
      interesting feature of the present case is that it is the only reported case of a
      newborn that was treated by supplementation of the mother.

PMID- 20051935
TI  - A novel mutation of cystathionine beta-synthase gene in a Thai boy with
      homocystinuria.
AB  - The authors reported a 14-year-old boy who presented with multiple organs
      thrombosis and subluxation of lens. His diagnosis of homocystinuria was delayed
      owing to the unrecognition of the disease resulting in significant morbidity. The
      mutation analysis showed one novel mutation that can explain the high level of
      plasma homocysteine.

PMID- 20051936
TI  - Red wine: can you have too much of a good thing?

PMID- 20051937
TI  - Single-cell suction recordings from mouse cone photoreceptors.
AB  - Rod and cone photoreceptors in the retina are responsible for light detection. In
      darkness, cyclic nucleotide-gated (CNG) channels in the outer segment are open
      and allow cations to flow steadily inwards across the membrane, depolarizing the
      cell. Light exposure triggers the closure of the CNG channels, blocks the inward
      cation current flow, and thus results in cell hyperpolarization. Based on the
      polarity of photoreceptors, a suction recording method was developed in 1970s
      that, unlike the classic patch-clamp technique, does not require penetrating the
      plasma membrane. Drawing the outer segment into a tightly-fitting glass pipette
      filled with extracellular solution allows recording the current changes in
      individual cells upon test-flash exposure. However, this well-established "outer
      segment-in (OS-in)" suction recording is not suitable for mouse cone recordings,
      because of the low percentage of cones in the mouse retina (3%) and the
      difficulties in identifying the cone outer segments. Recently, an inner-segment
      in (IS-in) recording configuration was developed to draw the inner
      segment/nuclear region of the photoreceptor into the recording pipette. In this
      video, we will show how to record from individual mouse cone photoresponses using
      single-cell suction electrode.

PMID- 20051938
TI  - Enhanced antitumor effects of an engineered measles virus Edmonston strain
      expressing the wild-type N, P, L genes on human renal cell carcinoma.
AB  - Measles virus Edmonston strain (MV-Edm) is thought to have remarkable oncolytic
      activity that selectively destroys human tumor cells. The P/V/C protein of wild
      type MV was shown to resist the antiviral effects of interferon (IFN)-alpha.
      Here, we engineered new MVs by arming MV-Edm tag strain (a V-defective vaccine
      lineage strain, MV-Etag) with the P or N, P, and L genes of wild-type MV (MV-P
      and MV-NPL, respectively). The oncolytic activities of the MVs were determined in
      human renal cell carcinoma (RCC) cell lines and primary human RCC cells by the
      MTT assay. The antitumor efficacy of the MVs was evaluated in A-498 xenografts in
      nude mice. IFN-alpha effectively inhibited the replication of MV-Etag and MV-P,
      but not MV-NPL. MV-NPL more efficiently induced cytopathic effects (CPEs) in OS
      RC-2 cells, even in the presence of human IFN-alpha. MV-NPL replicated more
      rapidly than MV-P and MV-Etag in A-498 cells. Apoptosis was induced earlier in A
      498 cells by MV-NPL than MV-Etag and MV-P. MV-NPL showed more significant
      antitumoral effects and had prolonged replication compared to MV-Etag and MV-P.
      In this study, we demonstrated that the newly engineered MV-NPL has more
      effective oncolytic activity and may help establish an innovative cancer therapy.

PMID- 20051939
TI  - Inhibition of tumor growth and metastasis by a combination of Escherichia coli
      mediated cytolytic therapy and radiotherapy.
AB  - We have reported that Escherichia coli K-12 colonizes hypoxic and necrotic tumor
      regions after intravenous injection into tumor-bearing mice. In this study, we
      established a novel strategy for cancer therapy using engineered bacteria to
      enhance the therapeutic effects of radiation. E. coli strain K-12 was engineered
      to produce cytolysin A (ClyA), and its effects on tumor growth in primary and
      metastatic tumor models were evaluated. A single treatment with E. coli
      expressing ClyA significantly decreased tumor growth rates initially (9 days
      after treatment); however, the tumors tended to grow thereafter. With only
      radiotherapy (RT; 21 Gy), the tumor growth rates were retarded, but not the tumor
      sizes. A combination of therapy with E. coli-expressing ClyA and radiation [a
      total of 5 x 10(7) colony-forming units (CFU) and 21 Gy] resulted in significant
      tumor shrinkage and even complete disappearance of tumors in mice with tumors
      derived from murine CT26 colon cancer. Furthermore, treatment with E. coli
      expressing ClyA markedly suppressed metastatic tumor growth and prolonged the
      survival time in mice. The results described here indicate that therapy with
      engineered E. coli could significantly improve the results of RT, and could exert
      a striking inhibitory effect on the development of lung metastasis.

PMID- 20051940
TI  - Lentivirus immobilization to nanoparticles for enhanced and localized delivery
      from hydrogels.
AB  - Hydrogels can provide a controllable cell microenvironment for numerous
      applications in regenerative medicine, and delivery of gene therapy vectors can
      be employed to enhance their bioactivity. We investigated the delivery of
      lentiviral vectors from hydrogels, and employed the immobilization of lentivirus
      to hydroxylapatite (HA) nanoparticles as a means to retain and stabilize vectors
      within hydrogels, and thereby increase delivery efficiency. Entrapment of the
      vector alone within the hydrogel maintained the activity of the virus more
      effectively compared to the absence of a hydrogel, and release was slowed with an
      increasing solid content of the hydrogel. Association of the lentivirus with HA
      increased the activity of the complexes, with HA increasing the virus activity
      for 72 hours. Cells seeded onto lentivirus-HA-loaded hydrogels had a decreased
      number of infected cells outside of the hydrogel relative to the absence of HA.
      In vivo studies with collagen hydrogels loaded with lentivirus and HA-lentivirus
      demonstrated sustained and localized transgene expression for at least 4 weeks,
      with increased expression using the lentivirus-HA complex. This strategy of
      nanoparticle immobilization to stabilize and retain vectors is broadly applicable
      to hydrogels, and may provide a versatile tool to combine gene therapy and
      biomaterials for applications in regenerative medicine.

PMID- 20051941
TI  - High cancer risk in Peutz-Jeghers syndrome: a systematic review and surveillance
      recommendations.
AB  - OBJECTIVES: Peutz-Jeghers syndrome (PJS) is an autosomal dominant inherited
      disorder associated with increased cancer risk. Surveillance and patient
      management are, however, hampered by a wide range in cancer risk estimates. We
      therefore performed a systematic review to assess cancer risks in PJS patients
      and used these data to develop a surveillance recommendation. METHODS: A
      systematic PubMed search was performed up to February 2009, and all original
      articles dealing with PJS patients with confirmed cancer diagnoses were included.
      Data involving cancer frequencies, mean ages at cancer diagnosis, relative risks
      (RRs), and cumulative risks were collected. RESULTS: Twenty-one original
      articles, 20 cohort studies, and one meta-analysis fulfilled the inclusion
      criteria. The cohort studies showed some overlap in the patient population and
      included a total of 1,644 patients; 349 of them developed 384 malignancies at an
      average age of 42 years. The most common malignancy was colorectal cancer,
      followed by breast, small bowel, gastric, and pancreatic cancers. The reported
      lifetime risk for any cancer varied between 37 and 93%, with RRs ranging from 9.9
      to 18 in comparison with the general population. Age-related cumulative risks
      were given for any cancer and gastrointestinal, gynecological, colorectal,
      pancreatic, and lung cancers. CONCLUSIONS: PJS patients are markedly at risk for
      several malignancies, in particular gastrointestinal cancers and breast cancer.
      On the basis of these elevated risks, a surveillance recommendation is developed
      to detect malignancies in an early phase and to remove polyps that may be
      premalignant and may cause complications, so as to improve the outcome.

PMID- 20051942
TI  - Prospective multicenter trial comparing push-and-pull enteroscopy with the single
      and double-balloon techniques in patients with small-bowel disorders.
AB  - OBJECTIVES: Double-balloon enteroscopy (DBE) is now an established method for
      diagnostic and therapeutic small-bowel endoscopy. Single-balloon enteroscopy
      (SBE) has been introduced to simplify the technique. A prospective randomized
      study was carried out to compare the two methods. METHODS: The study included 100
      patients (50 in each group; 63 men, 37 women; mean age 55 years), with no
      previous small-bowel or colon surgery. The indications for enteroscopy were
      (suspected) mid-gastrointestinal bleeding, Crohn's disease, small-bowel masses,
      chronic diarrhea or abdominal pain or both, and other conditions. Fujinon
      instruments were used, with either two balloons or one. The end point of the
      study was complete enteroscopy as the most objective parameter. RESULTS: No
      severe complications such as perforation, bleeding, or pancreatitis occurred.
      Instrument preparation time was significantly faster with SBE than with DBE
      (P<0.0001). Complete enteroscopy was achieved with the DBE technique in 66% of
      cases (33 patients), either with the oral route alone or with combined oral and
      anal approaches. With the SBE technique, the complete enteroscopy rate was
      significantly lower at 22% (P<0.0001; 11 patients, only with oral and anal routes
      combined). The rate of therapeutic consequences for the patients based on
      diagnostic yield and negative complete enteroscopy was significantly higher
      (P=0.025) in the DBE group at 72%, compared with 48% in the SBE group.
      CONCLUSIONS: The complete enteroscopy rate was three times higher with DBE than
      with SBE, accompanied by a higher diagnostic yield. DBE must therefore continue
      to be regarded as the nonsurgical gold standard procedure for deep small-bowel
      endoscopy.

PMID- 20051943
TI  - Predicting mortality in non-variceal upper gastrointestinal bleeders: validation
      of the Italian PNED Score and Prospective Comparison with the Rockall Score.
AB  - OBJECTIVES: We sought (i) to validate a new prediction rule of mortality
      (Progetto Nazionale Emorragia Digestiva (PNED) score) on an independent
      population with non-variceal upper gastrointestinal bleeding (UGIB) and (ii) to
      compare the accuracy of the Italian PNED score vs. the Rockall score in
      predicting the risk of death. METHODS: We conducted prospective validation of
      analysis of consecutive patients with UGIB at 21 hospitals from 2007 to 2008.
      Outcome measure was 30-day mortality. All the variables used to calculate the
      Rockall score as well as those identified in the Italian predictive model were
      considered. Calibration of the model was tested using the chi2 goodness-of-fit
      and performance characteristics with receiver operating characteristic (ROC)
      analysis. The area under the ROC curve (AUC) was used to quantify the diagnostic
      accuracy of the two predictive models. RESULTS: Over a 16-month period, data on
      1,360 patients were entered in a national database and analyzed. Peptic ulcer
      bleeding was recorded in 60.7% of cases. One or more comorbidities were present
      in 66% of patients. Endoscopic treatment was delivered in all high-risk patients
      followed by high-dose intravenous proton pump inhibitor in 95% of them. Sixty-six
      patients died (mortality 4.85%; 3.54-5.75). The PNED score showed a high
      discriminant capability and was significantly superior to the Rockall score in
      predicting the risk of death (AUC 0.81 (0.72-0.90) vs. 0.66 (0.60-0.72),
      P<0.000). Positive likelihood ratio for mortality in patients with a PNED risk
      score >8 was 16.05. CONCLUSIONS: The Italian 10-point score for the prediction of
      death was successfully validated in this independent population of patients with
      non-variceal gastrointestinal bleeding. The PNED score is accurate and superior
      to the Rockall score. Further external validation at the international level is
      needed.

PMID- 20051944
TI  - Neither diabetes mellitus nor overweight is a risk factor for hepatocellular
      carcinoma in a dual HBV and HCV endemic area: community cross-sectional and case
      control studies.
AB  - OBJECTIVES: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections are well-known risk factors for hepatocellular carcinoma, and diabetes
      mellitus (DM) and overweight have also been reported as risk factors for
      hepatocellular carcinoma (HCC). We tried to elucidate the roles of DM and
      overweight in HCC development in a dual HBV and HCV endemic area of southern
      Taiwan. METHODS: In 2004, a community-based comprehensive screening program was
      conducted in Tainan County. Hepatitis B surface antigen (HBsAg), anti-HCV, alpha
      fetoprotein, complete blood counts, triglyceride, cholesterol, and glucose levels
      were examined. DM was defined as fasting blood sugar >126 mg per 100 ml, and
      overweight was defined as a body mass index >24 kg m(-2). Subjects with
      thrombocytopenia (platelet count <150 x 10(9) l(-1)) and elevated alpha
      fetoprotein (>20 ng ml(-1)) underwent ultrasonographic screening for HCC. A total
      of 56,307 adults (>40 years old) participated, and 72 new HCC cases were detected
      and confirmed. RESULTS: In comparisons of all 72 HCC cases with the other 144
      individual age-, sex-, residency-, HBsAg-, and anti-HCV-matched controls, only
      thrombocytopenia and high alanine transaminase (ALT) levels were shown to be
      independent risk factors. Neither DM nor overweight was shown to be significant
      in any of the analyses. CONCLUSIONS: On the basis of the community-based cross
      sectional and case-controlled studies, neither DM nor overweight was a risk
      factor for HCC in a dual HBV and HCV endemic area. However, male gender, age (>
      or =65 years), HBsAg, anti-HCV, thrombocytopenia, and high ALT levels were
      independent risk factors for HCC.

PMID- 20051945
TI  - Performance of clinical guidelines compared with molecular tumour screening
      methods in identifying possible Lynch syndrome among colorectal cancer patients:
      a Norwegian population-based study.
AB  - BACKGROUND: The aim of this study was to assess the performance of the Revised
      Bethesda Guidelines (RBG) and the accuracy of the Amsterdam II criteria (AM II)
      in identifying possible Lynch syndrome (LS) compared with the results of
      molecular tumour testing. METHODS: Tumours from 336 unselected colorectal cancer
      patients were analysed by three molecular tests (namely microsatellite
      instability (MSI), BRAF mutation and methylation of mismatch-repair genes), and
      patients were classified according to the RBG and AM II criteria. RESULTS: A
      total of 87 (25.9%) patients fulfilled the RBG for molecular tumour analyses (MSI
      and/or immunohistochemistry), and the AM II identified 8 (2.4%) patients as
      having possible LS. Molecular tests identified 12 tumours (3.6%) as probable LS.
      The RBG identified 6 of the 12 patients (sensitivity 50%), whereas 5 of the 8
      patients who fulfilled the AM II criteria were not likely to be LS, based on
      molecular tests (predictive value of positive test, 38%). INTERPRETATION:
      Assuming a fairly high accuracy of molecular testing, the performance of the RBG
      in identifying patients with possible LS was poor, and the AM II criteria falsely
      identified a large proportion as having possible LS. This favours the use of
      molecular testing in the diagnosis of possible LS.

PMID- 20051946
TI  - What is a reasonable cost to refute a preposterous hypothesis?

PMID- 20051947
TI  - Genome-wide DNA methylation profiling reveals novel epigenetically regulated
      genes and non-coding RNAs in human testicular cancer.
AB  - BACKGROUND: Testicular germ cell tumour (TGCT) is the most common malignant
      tumour in young males. Although aberrant DNA methylation is implicated in the
      pathophysiology of many cancers, only a limited number of genes are known to be
      epigenetically changed in TGCT. This report documents the genome-wide analysis of
      differential methylation in an in vitro model culture system. Interesting genes
      were validated in TGCT patient samples. METHODS: In this study, we used
      methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to
      identify differentially methylated regions (DMRs). RESULTS: We identified 35 208
      DMRs. However, only a small number of DMRs mapped to promoters. A genome-wide
      analysis of gene expression revealed a group of differentially expressed genes
      that were regulated by DNA methylation. We identified several candidate genes,
      including APOLD1, PCDH10 and RGAG1, which were dysregulated in TGCT patient
      samples. Surprisingly, APOLD1 had previously been mapped to the TGCT
      susceptibility locus at 12p13.1, suggesting that it may be important in TGCT
      pathogenesis. We also observed aberrant methylation in the loci of some non
      coding RNAs (ncRNAs). One of the ncRNAs, hsa-mir-199a, was downregulated in TGCT
      patient samples, and also in our in vitro model culture system. CONCLUSION: This
      report is the first application of MeDIP-chip for identifying epigenetically
      regulated genes and ncRNAs in TGCT. We also demonstrated the function of
      intergenic and intronic DMRs in the regulation of ncRNAs.

PMID- 20051948
TI  - Trends in incidence of childhood cancer in Australia, 1983-2006.
AB  - BACKGROUND: There are few population-based childhood cancer registries in the
      world containing stage and treatment data. METHODS: Data from the population
      based Australian Paediatric Cancer Registry were used to calculate incidence
      rates during the most recent 10-year period (1997-2006) and trends in incidence
      between 1983 and 2006 for the 12 major diagnostic groups of the International
      Classification of Childhood Cancer. RESULTS: In the period 1997-2006, there were
      6184 childhood cancer (at 0-14 years) cases in Australia (157 cases per million
      children). The commonest cancers were leukaemia (34%), that of the central
      nervous system (23%) and lymphomas (10%), with incidence the highest at 0-4 years
      (223 cases per million). Trend analyses showed that incidence among boys for all
      cancers combined increased by 1.6% per year from 1983 to 1994 but have remained
      stable since. Incidence rates for girls consistently increased by 0.9% per year.
      Since 1983, there have been significant increases among boys and girls for
      leukaemia, and hepatic and germ-cell tumours, whereas for boys, incidence of
      neuroblastomas and malignant epithelial tumours has recently decreased. For all
      cancers and for both sexes combined, there was a consistent increase (+0.7% per
      year, 1983-2006) at age 0-4 years, a slight non-significant increase at 5-9
      years, and at 10-14 years, an initial increase (2.7% per year, 1983-1996)
      followed by a slight non-significant decrease. CONCLUSION: Although there is some
      evidence of a recent plateau in cancer incidence rates in Australia for boys and
      older children, interpretation is difficult without a better understanding of
      what underlies the changes reported.

PMID- 20051949
TI  - Considerations for the use of plasma cytokeratin 18 as a biomarker in pancreatic
      cancer.
AB  - BACKGROUND: Enzyme-linked immunoassays of full-length (M65) and/or caspase
      cleaved (M30) cytokeratin 18 (CK18) released from epithelial cells undergoing
      necrosis and/or apoptosis, respectively, may have prognostic or predictive
      biomarker utility in a range of solid tumour types. Characterisation of baseline
      levels of circulating full length and cleaved CK18 specifically in patients with
      pancreatic cancer. METHODS: Plasma samples from 103 patients with pancreatic
      cancer stored at -80 degrees C were assayed for M65 and M30 levels. The median
      (inter-quartile range (IQR)) duration of plasma storage was 34 (23-57) months.
      Patients with metastatic disease (n=19) were found to have greater median (IQR)
      M65 levels (1145 (739-1698) U l(-1)) compared with the locally advanced (n=20;
      748 (406-1150) U l(-1)) and resected (n=64; 612 (331-987) U l(-1)) patients
      (P=0.002). Elevated M65 levels were associated with poorer overall survival on
      univariate (P<0.001) but not multivariate (P=0.202) analysis. M65 concentrations
      also exhibited significant associations with concurrent serum-bilirubin levels
      (P<0.001) and the duration of plasma storage (P<0.001). CONCLUSIONS: Baseline
      plasma CK18 levels in pancreatic cancer are affected by the presence of
      obstructive jaundice and prolonged plasma storage. Clinical biomarker studies
      utilising serial CK18 levels are warranted in pancreatic cancer, provided
      consideration is given to these potentially confounding factors.

PMID- 20051950
TI  - Co-detection of members of the urokinase plasminogen activator system in tumour
      tissue and serum correlates with a poor prognosis for soft-tissue sarcoma
      patients.
AB  - BACKGROUND: The urokinase plasminogen activator (uPA) system is one of the best
      investigated protease systems, both under physiological and pathological
      conditions, including various types of cancer. However, effects of co-expression
      of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein
      level in both tumour tissue and serum have not been investigated yet. METHODS: We
      examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumour
      tissue and serum by ELISA. RESULTS: A significant correlation between high
      antigen levels of uPA, PAI-1 or uPAR in tumour tissue, and of uPAR in serum, with
      poor outcome of STS patients was found for the first time. Most strikingly, we
      observed an additive effect of combined uPA, PAI-1 or uPAR levels in tumour
      tissue extracts with uPAR levels in serum on patients' prognosis. High uPA/uPAR,
      PAI-1/uPAR and uPAR/uPAR antigen levels in tumour tissue/serum were associated
      with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumour-related death
      (P=0.003, 0.001 and 0.002, respectively) compared with those patients who
      displayed low levels of the respective marker combination. CONCLUSION: As
      expression of members of the uPA system in tumour tissue and serum is additively
      correlated with prognosis of STS patients, our results suggest that combinations
      of these biomarkers can identify STS patients with a higher risk of tumour
      related death.

PMID- 20051951
TI  - False-positive screening results in the Finnish prostate cancer screening trial.
AB  - BACKGROUND: There is evidence that prostate cancer (PC) screening with prostate
      specific antigen (PSA) serum test decreases PC mortality, but screening has
      adverse effects, such as a high false-positive (FP) rate. We investigated the
      proportion of FPs in a population-based randomised screening trial in Finland.
      METHODS: Finland is the largest centre in the European Randomized Study of
      Screening for Prostate Cancer. We have completed three screening rounds with a 4
      year screening interval (mean follow-up time 9.2 years) using a PSA cutoff level
      of 4.0 ng ml(-1); in addition, men with PSA 3.0-3.9 and a positive auxiliary test
      were referred. An FP result was defined as a positive screening result without
      cancer in biopsy within 1 year from the screening test. RESULTS: The proportion
      of FP screening results varied from 3.3 to 12.1% per round. Of the screened men,
      12.5% had at least one FP during three rounds. The risk of next-round PC
      following an FP result was 12.3-19.7 vs 1.4-3.7% following a screen-negative
      result (depending on the screening round), risk ratio 3.6-9.9. More than half of
      the men with one FP result had another one at a subsequent screen. Men with an FP
      result were 1.5 to 2.0 times more likely to not participate in subsequent rounds
      compared with men with a normal screening result (21.6-29.6 vs 14.0-16.7%).
      CONCLUSION: An FP result is a common adverse effect of PC screening and affects
      at least every eighth man screened repeatedly, even when using a relatively high
      cutoff level. False-positive men constitute a special group that receives
      unnecessary interventions but may harbour missed cancers. New strategies are
      needed for risk stratification in PC screening to minimise the proportion of FP
      men.

PMID- 20051952
TI  - Combination therapy: intermittent sorafenib with bevacizumab yields activity and
      decreased toxicity.
AB  - BACKGROUND: We previously reported preliminary results of our phase I study of
      continuous daily sorafenib with bevacizumab every other week for solid tumours.
      Toxicity was moderate, leading to additional dose levels (DL) testing
      intermittent sorafenib dosing. METHODS: Seventeen patients with advanced solid
      tumours were treated on three additional DLs testing sorafenib days 1-5 per week.
      Dose level 4 was sorafenib 200 mg twice daily (b.i.d.) and bevacizumab 5 mg kg(
      1). DL5 alternated between bevacizumab 10 mg kg(-1)-sorafenib 200 mg b.i.d. (A)
      and sorafenib 400 mg b.i.d. with bevacizumab 5 mg kg(-1) (B). Outcome and
      toxicity data from 19 epithelial ovarian cancer (EOC) patients from DL 1-5 were
      analysed. RESULTS: Fewer patients required sorafenib dose reduction with the
      intermittent schedule (41 vs 74% daily, P=0.01). Hand-foot skin reaction (HFSR)
      remained the primary cause of dose reduction (n=5). Partial responses (12%) or
      disease stabilisation > or =4 months (53%; median 6 (4-26)) occurred in most
      patients on the intermittent schedule. Partial response occurred in 47% EOC
      patients treated in pooled analysis of duration 4-37 months. CONCLUSION:
      Intermittent sorafenib dosing with bevacizumab has promising clinical activity
      and less sorafenib dose reduction and side effects, but does not ameliorate HFSR.
      We are conducting a phase II clinical trial with intermittent sorafenib and
      bevacizumab in patients with EOC.

PMID- 20051953
TI  - Radiological and pathological size estimations of pure ductal carcinoma in situ
      of the breast, specimen handling and the influence on the success of breast
      conservation surgery: a review of 2564 cases from the Sloane Project.
AB  - BACKGROUND: The Sloane Project, an audit of UK screen-detected non-invasive
      carcinomas and atypical hyperplasias of the breast, has accrued over 5000 cases
      in 5 years; with paired radiological and pathological data for 2564 ductal
      carcinoma in situ (DCIS) cases at the point of this analysis. We have compared
      the radiological estimate of DCIS size with the pathological estimate of DCIS
      size. We have correlated these sizes with histological grade, specimen-handling
      methods, particularly the use of specimen slice radiographs, and the success or
      failure of breast-conserving surgery (BCS). METHODS: The Sloane Project database
      was interrogated to extract information on all patients diagnosed with DCIS with
      complete radiological and pathological data on the size of DCIS, nuclear grade,
      specimen handling (with particular reference to specimen radiographs) and whether
      primary BCS was successful or whether the patient required further conservation
      surgery or a mastectomy. RESULTS: Of 2564 patients in the study, 2013 (79%) had
      attempted BCS and 1430 (71%) had a successful single operation. Of the 583 BCS
      patients who required further surgery, 65% had successful conservation and 97% of
      them after a single further operation. In successful one-operation BCS patients,
      there was a close agreement between radiological and pathological DCIS size with
      radiology tending to marginally overestimate the disease extent. In multiple
      operation BCS, radiology underestimated DCIS size in 59% of cases. The agreement
      between pathological and radiological size of DCIS was poor in mastectomies but
      was improved by specimen slice radiography, suggesting specimen-handling
      techniques as a cause. CONCLUSION: In 30% of patients undergoing BCS for DCIS,
      preoperative imaging underestimates the extent of disease resulting in a
      requirement for further surgery. This has implications for the further
      improvement of preoperative imaging and non-operative diagnosis of DCIS so that
      second operations are reduced to a minimum.

PMID- 20051954
TI  - EWS-Oct-4B, an alternative EWS-Oct-4 fusion gene, is a potent oncogene linked to
      human epithelial tumours.
AB  - BACKGROUND: Characterisation of EWS-Oct-4 translocation fusion product in bone
      and soft-tissue tumours revealed a chimeric gene resulting from an in-frame
      fusion between EWS (Ewing's sarcoma gene) exons 1-6 and Oct-4 exons 1-4.
      Recently, an alternative form of the fusion protein between the EWS and Oct-4
      genes, named EWS-Oct-4B, was reported in two types of epithelial tumours, a
      hidradenoma of the skin and a mucoepidermoid carcinoma of the salivary glands. As
      the N-terminal and POU domains of the EWS-Oct-4 and EWS-Oct-4B proteins are not
      structurally identical, we decided to investigate the functional consequences of
      the EWS-Oct-4B fusion. METHODS: In this report, we have characterised the EWS-Oct
      4B fusion protein. To investigate how the EWS-Oct-4B protein contributes to
      tumourigenesis in human cancers, we analysed its DNA-binding activity,
      subcellular localisation, transcriptional activation behaviour, and oncogenic
      properties. RESULTS: We found that this new chimeric gene encodes a nuclear
      protein that binds DNA with the same sequence specificity as the parental Oct-4
      protein or the fusion EWS-Oct-4 protein. We show that the nuclear localisation
      signal of EWS-Oct-4B is dependent on the POU DNA-binding domain, and we
      identified a cluster of basic amino acids, (269)RKRKR(273), in the POU domain
      that specifically mediates the nuclear localisation of EWS-Oct-4B. Comparison of
      the properties of EWS-Oct-4B and EWS-Oct-4 indicated that EWS-Oct-4B is a less
      potent transcriptional activator of a reporter construct carrying the Oct-4
      binding sites. Deletion analysis of the functional domains of EWS-Oct-4B revealed
      that the EWS N-terminal domain (NTD)(B), POU, and C-terminal domain (CTD) are
      necessary for its full transactivation potential. Despite its reduced activity as
      a transcriptional activator, EWS-Oct-4B regulated the expression of fgf-4
      (fibroblast growth factor-4) and nanog, which are potent mitogens, as well as of
      Oct-4 downstream target genes, the promoters of which contain potential Oct-4
      binding sites. Finally, ectopic expression of EWS-Oct-4B in Oct-4-null ZHBTc4 ES
      cells resulted in increased tumourigenic growth potential in nude mice.
      CONCLUSION: These results suggest that the oncogenic effect of the t(6;22)
      translocation is due to the EWS-Oct-4B chimeric protein, and that alternative
      fusion of the EWS amino terminal domain to the Oct-4 DNA-binding domain produces
      another transforming chimeric product in human epithelial tumours.

PMID- 20051955
TI  - Choline and betaine intake and risk of breast cancer among post-menopausal women.
AB  - BACKGROUND: Choline and betaine, similar to folate, are nutrients involved in one
      carbon metabolism and hypothesised to reduce breast cancer risk. No prospective
      study among post-menopausal women has examined choline and betaine intakes in
      relation to breast cancer risk. METHODS: We examined the intake of choline and
      betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses'
      Health Study. Nutrient intake was assessed using a validated food-frequency
      questionnaire six times since 1984. During 20 years of follow-up from 1984 until
      2004, we documented 3990 incident cases of invasive breast cancer. RESULTS:
      Overall, choline (mean+/-s.d.; 326+/-61 mg per day) and betaine (104+/-33 mg per
      day) intake was not associated with a reduced risk of post-menopausal breast
      cancer. Participants in the highest quintile of intakes had multivariate relative
      risks of 1.10 (95% confidence interval (95% CI): 0.99-1.22; P-value, test for
      trend=0.14) for choline and 0.98 (95% CI: 0.89-1.09; P-value, test for
      trend=0.96) for betaine, compared with those in the lowest quintiles of intakes.
      The results were similar in breast cancer stratified by hormone receptor
      (oestrogen receptor/progesterone receptor) status. The association between
      choline intake and breast cancer risk did not differ appreciably by alcohol
      intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk
      factors, including family history of breast cancer, history of benign breast
      disease, body mass index, post-menopausal hormone use, and folate intake.
      CONCLUSION: We found no evidence that higher intakes of choline and betaine
      reduce risk of breast cancer among post-menopausal women.

PMID- 20051956
TI  - The role of folate receptor alpha (FRalpha) in the response of malignant pleural
      mesothelioma to pemetrexed-containing chemotherapy.
AB  - BACKGROUND: The standard treatment of choice for malignant pleural mesothelioma
      is chemotherapy with pemetrexed and platinum, but the clinical outcome is poor.
      This study investigates the response to pemetrexed in a panel of eight
      mesothelioma cell lines and the clinical outcome for patients treated with
      pemetrexed in relation to folate receptor alpha (FRalpha). METHODS: Cell lines
      were treated with pemetrexed to determine the concentration that reduced growth
      to 50% (GI(50)). FRalpha expression was determined by western blotting and that
      of FRalpha, reduced folate carrier (RFC) and proton-coupled folate transporter
      (PCFT) by real-time quantitative RT-PCR. Immunohistochemistry for FRalpha was
      carried out on 62 paraffin-embedded samples of mesothelioma from patients who
      were subsequently treated with pemetrexed. RESULTS: A wide range of GI(50) values
      was obtained for the cell lines, H2452 cells being the most sensitive (GI(50) 22
      nM) and RS5 cells having a GI(50) value greater than 10 microM. No FRalpha
      protein was detected in any cell line, and there was no relationship between
      sensitivity and expression of folate transporters. FRalpha was detected in 39% of
      tumour samples, generally in a small percentage of cells. There was no
      correlation between the presence of FRalpha and the outcome of pemetrexed
      treatment, and no significant difference between histological subtypes.
      CONCLUSION: Response to treatment with pemetrexed does not depend on the presence
      of FRalpha.

PMID- 20051957
TI  - Circulating tumour cells demonstrate an altered response to hypoxia and an
      aggressive phenotype.
AB  - BACKGROUND: Tumours contain hypoxic regions that select for an aggressive cell
      phenotype; tumour hypoxia induces metastasis-associated genes. Treatment
      refractory patients with metastatic cancer show increased numbers of circulating
      tumour cells (CTCs), which are also associated with disease progression. The aim
      of this study was to examine the as yet unknown relationship between hypoxia and
      CTCs. METHODS: We generated human MDA-MB-231 orthotopic xenografts and, using a
      new technology, isolated viable human CTCs from murine blood. The CTCs and
      parental MDA-MB-231 cells were incubated at 21 and 0.2% (hypoxia) oxygen,
      respectively. Colony formation was assayed and levels of hypoxia- and anoxia
      inducible factors were measured. Xenografts generated from CTCs and parental
      cells were compared. RESULTS: MDA-MB-231 xenografts used to generate CTCs were
      hypoxic, expressing hypoxia factors: hypoxia-inducible factor1 alpha (HIF1alpha)
      and glucose transporter protein type 1 (GLUT1), and anoxia-induced factors:
      activating transcription factor 3 and 4 (ATF3 and ATF4). Parental MDA-MB-231
      cells induced ATF3 in hypoxia, whereas CTCs expressed it constitutively.
      Asparagine synthetase (ASNS) expression was also higher in CTCs. Hypoxia induced
      ATF4 and the HIF1alpha target gene apelin in CTCs, but not in parental cells.
      Hypoxia induced lower levels of carbonic anhydrase IX (CAIX), GLUT1 and
      BCL2/adenovirus E1B 19-KD protein-interacting protein 3 (BNIP3) proteins in CTCs
      than in parental cells, supporting an altered hypoxia response. In chronic
      hypoxia, CTCs demonstrated greater colony formation than parental cells.
      Xenografts generated from CTCs were larger and heavier, and metastasised faster
      than MDA-MB-231 xenografts. CONCLUSION: CTCs show an altered hypoxia response and
      an enhanced aggressive phenotype in vitro and in vivo.

PMID- 20051958
TI  - Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of
      survival and other safety outcomes.
AB  - BACKGROUND: Cancer patients often develop the potentially debilitating condition
      of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating
      agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in
      anaemic cancer patients receiving chemotherapy. To evaluate recent safety
      concerns regarding ESAs, we carried out a meta-analysis of controlled ESA
      oncology trials to examine whether ESA use affects survival, disease progression
      and risk of venous-thromboembolic events. METHODS: This meta-analysis included
      studies from the 2006 Cochrane meta-analysis, studies published/updated since the
      2006 Cochrane report, and unpublished trial data from Amgen and Centocor Ortho
      Biotech. The 60 studies analysed (15 323 patients) were conducted in the settings
      of chemotherapy/radiochemotherapy, radiotherapy only treatment or anaemia of
      cancer. Data were summarised using odds ratios (ORs) with 95% confidence
      intervals (CIs). RESULTS: Results indicated that ESA use did not significantly
      affect mortality (60 studies: OR=1.06; 95% CI: 0.97-1.15) or disease progression
      (26 studies: OR=1.01; 95% CI: 0.90-1.14), but increased the risk for venous
      thromoboembolic events (44 studies: OR=1.48; 95% CI: 1.28-1.72). CONCLUSION:
      Though this meta-analysis showed no significant effect of ESAs on survival or
      disease progression, prospectively designed, future randomised clinical trials
      will further examine the safety and efficacy of ESAs when used according to the
      revised labelling information.

PMID- 20051959
TI  - C20orf20 (MRG-binding protein) as a potential therapeutic target for colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancer is one of the most common causes of cancer death
      worldwide. Using cDNA microarray containing 23 040 genes, we earlier investigated
      gene-expression profiles in 11 colorectal cancers for the purpose of better
      understanding of colorectal carcinogenesis as well as development of novel
      diagnostic and therapeutic strategies. MRG-binding protein (MRGBP) or C20orf20,
      encoding a subunit of TRRAP/TIP60-containing histone acetyltransferase complex,
      was up-regulated in the majority of colorectal tumours. METHODS AND RESULTS: The
      elevated expression of MRGBP was observed in colorectal cancer tissues by
      quantitative PCR as well as immunohistochemical analyses. MRGBP marginally
      expressed in normal vital organs. Notably, suppressed MRGBP expression by MRGBP
      short hairpin RNA inhibited proliferation of colorectal cancer cells. Yeast two
      hybrid screening and subsequent immunoprecipitation analysis identified
      bromodomain containing 8 (BRD8) as an MRGBP-interacting protein. As RNA
      interference against BRD8 also suppressed proliferation of colorectal cancer
      cells, BRD8 may be an important down-stream target of MRGBP. CONCLUSION: These
      results suggest that MRGBP has an important function in proliferation of cancer
      cells through the regulation of BRD8 and that MRGBP should be a novel therapeutic
      target for colorectal cancer.

PMID- 20051960
TI  - Two novel human anti-ErbB2 immunoagents are active on trastuzumab-resistant
      tumours.
AB  - BACKGROUND: Overexpression of ErbB2 receptor in breast cancer is associated with
      disease progression and poor prognosis. Trastuzumab, the only humanised anti
      ErbB2 antibody currently used in breast cancer, has proven to be effective;
      however, a relevant problem for clinical practice is that a high fraction of
      breast cancer patients shows primary or acquired resistance to trastuzumab
      treatment. METHODS: We tested on trastuzumab-resistant cells two novel human anti
      tumour immunoconjugates engineered in our laboratory by fusion of a human anti
      ErbB2 scFv, termed Erbicin, with either a human RNase or the Fc region of a human
      IgG1. Both Erbicin-derived immunoagents (EDIAs) are selectively cytotoxic for
      ErbB2-positive cancer cells in vitro and vivo, target an ErbB2 epitope different
      from that recognised by trastuzumab and do not show cardiotoxic effects. RESULTS:
      We report that EDIAs are active also on trastuzumab-resistant tumour cells both
      in vitro and in vivo, most likely because of the different epitope recognised, as
      EDIAs, unlike trastuzumab, were found to be able to inhibit the signalling
      pathway downstream of ErbB2. CONCLUSION: These results suggest that EDIAs are
      immunoagents that could not only fulfil the therapeutic need of patients
      ineligible to trastuzumab treatment due to cardiac dysfunction but also prove to
      be useful for breast cancer patients unresponsive to trastuzumab treatment.

PMID- 20051962
TI  - SUN vs BEVthornIFN in first-line mRCC therapy: no evidence for a statistically
      significant difference in progression-free survival.

PMID- 20051961
TI  - A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol
      1,3,4,5,6-pentakisphosphate.
AB  - BACKGROUND: Owing to its role in cancer, the phosphoinositide 3-kinase (PI3K)/Akt
      pathway is an attractive target for therapeutic intervention. We previously
      reported that the inhibition of Akt by inositol 1,3,4,5,6-pentakisphosphate
      (InsP(5)) results in anti-tumour properties. To further develop this compound we
      modified its structure to obtain more potent inhibitors of the PI3K/Akt pathway.
      METHODS: Cell proliferation/survival was determined by cell counting,
      sulphorhodamine or acridine orange/ethidium bromide assay; Akt activation was
      determined by western blot analysis. In vivo effect of compounds was tested on
      PC3 xenografts, whereas in vitro activity on kinases was determined by
      SelectScreen Kinase Profiling Service. RESULTS: The derivative 2-O-benzyl-myo
      inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP(5)) is active towards cancer
      types resistant to InsP(5) in vitro and in vivo. 2-O-Bn-InsP(5) possesses higher
      pro-apoptotic activity than InsP(5) in sensitive cells and enhances the effect of
      anti-cancer compounds. 2-O-Bn-InsP(5) specifically inhibits 3-phosphoinositide
      dependent protein kinase 1 (PDK1) in vitro (IC(50) in the low nanomolar range)
      and the PDK1-dependent phosphorylation of Akt in cell lines and excised tumours.
      It is interesting to note that 2-O-Bn-InsP(5) also inhibits the mammalian target
      of rapamycin (mTOR) in vitro. CONCLUSIONS: InsP(5) and 2-O-Bn-InsP(5) may
      represent lead compounds to develop novel inhibitors of the PI3K/Akt pathway
      (including potential dual PDK1/mTOR inhibitors) and novel potential anti-cancer
      drugs.

PMID- 20051964
TI  - Making progress as we enter the next decade.

PMID- 20051965
TI  - A poor view from specialty silos.

PMID- 20051966
TI  - Obesity: Intragastric balloons--a bubble to combat the obesity bubble?

PMID- 20051967
TI  - GERD: GERD and insomnia-first degree relatives or distant cousins?

PMID- 20051968
TI  - Gastrointestinal bleeding: Secondary prophylaxis for variceal bleeding.

PMID- 20051969
TI  - Liver: Does bariatric surgery reduce the severity of NAFLD?

PMID- 20051970
TI  - Epidemiology, pathogenesis and management of hepatitis D: update and challenges
      ahead.
AB  - Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is
      considered to be the most severe form of viral hepatitis in humans. Hepatitis D
      occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is
      a defective RNA viroid that requires HBsAg for transmission. At least eight
      different HDV genotypes have been described and each has a characteristic
      geographic distribution and a distinct clinical course. HDV and HBV coinfection
      can be associated with complex and dynamic viral dominance patterns. Chronic HDV
      infection leads to more severe liver disease than HBV monoinfection and is
      associated with accelerated fibrosis progression, earlier hepatic decompensation
      and an increased risk for the development of hepatocellular carcinoma. So far,
      only IFN-alpha treatment has proven antiviral activity against HDV in humans and
      has been linked to improved long-term outcomes. Studies conducted in the past 2
      years on the use of PEG-IFN-alpha show that a sustained virologic response to
      therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved
      in about one quarter of patients with hepatitis D. Novel alternative treatment
      options including prenylation inhibitors are awaiting clinical development for
      use in hepatitis D.

PMID- 20051971
TI  - Treatment of hepatocellular carcinoma with intra-arterial injection of
      radionuclides.
AB  - Hepatocellular carcinoma (HCC) is becoming an important public health concern.
      Current therapeutic options are limited and new treatments are therefore being
      developed. The intra-arterial treatment chemoembolization has limited efficacy
      and few prospects for further progress. One particularly promising, though little
      used, alternative to chemoembolization is radioembolization with iodine-131
      ((131)I) or rhenium-188 labeled lipiodol or yttrium-90 labeled microspheres
      (glass or resin beads). Three randomized studies have proven the effectiveness of
      (131)I-lipiodol in patients with HCC-as adjuvant therapy after surgery, compared
      with chemoembolization, and also in patients who have portal vein thrombosis.
      Microspheres enable the delivery of high-dose radiation (>200 Gy) to the tumor
      while sparing the neighboring hepatic tissue from overexposure. Overall, the
      efficacy of radioembolization has been good and toxic effects have been low.
      These results are comparable to those obtained with chemoembolization but further
      improvement can be expected by combining radioembolization with standard
      chemotherapy or with targeted therapies, such as anti-angiogenic drugs.

PMID- 20051972
TI  - Antifibrotic therapies--emerging biomarkers as treatment end points.
AB  - The emergence of novel pharmacologic therapies for hepatic fibrosis holds promise
      for the management of this condition. Furthermore, novel, biological indices-in
      addition to liver biopsy-may improve our ability to assess the unique
      pharmacological effects generated by these agents. This article will attempt to
      highlight the potential for emerging biomarkers to serve as end points in
      clinical studies that target salient features of hepatic fibrogenesis.

PMID- 20051973
TI  - Ascorbic acid prevents blood-brain barrier disruption and sensory deficit caused
      by sustained compression of primary somatosensory cortex.
AB  - Transient compression of rat somatosensory cortex has been reported to affect
      cerebral microvasculature and sensory function simultaneously. However, the
      effects of long-term cortical compression remain unknown. Here, we investigated
      whether and to what extent sustained but moderate epidural compression of rat
      somatosensory cortex impairs somatic sensation and/or cortical microvasculature.
      Electrophysiological and behavioral tests revealed that sustained compression
      caused only short-term sensory deficit, particularly at 1 day after injury.
      Although the diameter of cortical microvessels was coincidentally reduced, no
      ischemic insult was observed. By measuring Evans Blue and immunoglobulin G
      extravasation, the blood-brain barrier (BBB) permeability was found to
      dramatically increase during 1 to 3 days, but this did not lead to brain edema.
      Furthermore, immunoblotting showed that the BBB component proteins occludin,
      claudin-5, type IV collagen, and glial fibrillary acidic protein were markedly
      upregulated in the injured cortex during 1 to 2 weeks when BBB regained
      integrity. Conversely, treatment of ascorbic acid prevented compression-induced
      BBB disruption and sensory impairment. Together, these data suggest that
      sustained compression of the somatosensory cortex compromises BBB integrity and
      somatic sensation only in the early period. Ascorbic acid may be used
      therapeutically to modulate cortical compression and/or BBB dysfunction.

PMID- 20051974
TI  - Acute-stage diffusion-weighted magnetic resonance imaging for predicting outcome
      of poor-grade aneurysmal subarachnoid hemorrhage.
AB  - We investigated the role of acute-stage diffusion-weighted images (DWIs) for
      predicting outcome of poor-grade subarachnoid hemorrhage (SAH). This study
      included 38 patients with poor-grade SAH who underwent DWI within 24 h after
      onset. DWI findings were divided into three groups on the basis of lesion area:
      none (N), spotty (S, <or=10 mm(2)), or areal (A, >10 mm(2)). We evaluated the
      correlation between preoperative DWI findings and clinical outcome, and the
      characteristics of DWI abnormalities. DWI abnormalities were revealed in 81.6% of
      cases (group S 34.2%; group A 47.3%). All patients in groups N and S and 73.3% of
      patients in group A were treated radically. For those patients without rerupture,
      favorable outcomes were achieved in 100% of group N, 53.8% of group S, and 0% of
      group A. Abnormal lesions on initial DWI, which resulted in permanent lesions,
      showed a mean apparent diffusion coefficient ratio to the control value of 0.71,
      which was significantly lower than 0.95 observed in reversible lesions (P<0.01).
      We recommend radical treatment for even poor-grade SAH as long as the
      preoperative DWI shows no or only spotty lesions. DWI may provide an objective
      means to estimate the outcome of poor-grade SAH.

PMID- 20051975
TI  - Parkinson's disease spatial covariance pattern: noninvasive quantification with
      perfusion MRI.
AB  - Parkinson's disease (PD) is associated with elevated expression of a specific
      disease-related spatial covariance pattern (PDRP) in radiotracer scans of
      cerebral blood flow and metabolism. In this study, we scanned nine early-stage
      patients with PD and nine healthy controls using continuous arterial spin
      labeling (CASL) perfusion magnetic resonance imaging (pMRI). Parkinson's disease
      related metabolic pattern expression in CASL pMRI scans was compared with the
      corresponding (18)F-fluorodeoxyglucose positron emission tomography values. The
      PDRP expression was abnormally elevated (P<0.01) in patients scanned with either
      modality, and the two values were highly intercorrelated (P<0.0001). Perfusion
      MRI methods can be used for accurate quantification of disease-related covariance
      patterns.

PMID- 20051976
TI  - Statistics in experimental cerebrovascular research-comparison of two groups with
      a continuous outcome variable.
AB  - Part one of this mini-series on statistics in cerebrovascular research uses the
      simplest yet most common comparison in experimental research (two groups with a
      continuous outcome variable) to introduce the very basic concepts of statistical
      testing: a priori formulation of hypotheses and definition of planned statistical
      analysis, error considerations, and power analysis.

PMID- 20051978
TI  - An expectation-maximization algorithm for the Lasso estimation of quantitative
      trait locus effects.
AB  - The least absolute shrinkage and selection operator (Lasso) estimation of
      regression coefficients can be expressed as Bayesian posterior mode estimation of
      the regression coefficients under various hierarchical modeling schemes. A
      Bayesian hierarchical model requires hyper prior distributions. The regression
      coefficients are parameters of interest. The normal distribution assigned to each
      regression coefficient is a prior distribution. The variance parameter in the
      normal prior distribution is further assigned a hyper prior distribution so that
      the variance parameter can be estimated from the data. We developed an
      expectation-maximization (EM) algorithm to estimate the variance parameter of the
      prior distribution for each regression coefficient. Performance of the EM
      algorithm was evaluated through simulation study and real data analysis. We found
      that the Jeffreys' hyper prior for the variance component usually performs well
      with regard to generating the desired sparseness of the regression model. The EM
      algorithm can handle not only the usual regression models but it also
      conveniently deals with linear models in which predictors are defined as
      classification variables. In the context of quantitative trait loci (QTL)
      mapping, this new EM algorithm can estimate both genotypic values and QTL effects
      expressed as linear contrasts of the genotypic values.

PMID- 20051979
TI  - Focusing in on the small.

PMID- 20051977
TI  - Predictors of vitamin D biochemical status in a large sample of middle-aged male
      smokers in Finland.
AB  - BACKGROUND/OBJECTIVES: As vitamin D deficiency is considered to be more common in
      regions with little solar ultraviolet (UV) light in winter, the aim of this study
      was to analyze predictors of vitamin D status by season within a large sample of
      male smokers from Finland, a country where there is negligible solar UV light in
      winter. SUBJECTS/METHODS: Vitamin D (measured by 25-hydroxyvitamin D (25(OH)D)
      nmol/l) and other serum constituents were assayed. Measured anthropometry, and
      self-reported dietary intake and physical activity (PA) were obtained and
      analyzed using stepwise multiple linear and logistic regression in 2271 middle
      aged Finnish male smokers. RESULTS: In all, 27% of the population in winter and
      17% in summer had serum 25(OH)D levels of <25 nmol/l, respectively. In summer, in
      multiple logistic regression analyses with adjustment for confounding and other
      predictors, high vitamin D intake (odds ratios (OR) 3.6; 95% confidence interval
      (CI) 1.5-8.5), some leisure time PA (OR 2.0; 95% CI 1.3-3.1) and having a body
      mass index (BMI) of >or=21 kg/m(2) compared with <21 kg/m(2) (OR 2.6; 95% CI 1.3
      5.0), were associated with 25(OH)D >or=25 nmol/l. In winter, additional
      modifiable factors were occupational PA (OR 1.6; 95% CI 1.1-2.5) and high fish
      (OR 3.1; 95% CI 1.7-6.2) or poultry consumption (OR 1.7; 95% CI 1.2-2.5).
      Predictors from linear regression analyses of continuous levels of 25(OH)D were
      similar to the logistic regression analyses of 25(OH)D >or=25 nmol/l. CONCLUSION:
      In this Finnish sample more vitamin D intake, PA and having a BMI of >or=21 may
      have important modifiable roles in maintaining an adequate vitamin D status.

PMID- 20051980
TI  - Membrane transport proteins: surprises in structural sameness.

PMID- 20051982
TI  - MicroRNA assassins: factors that regulate the disappearance of miRNAs.
AB  - MicroRNAs (miRNAs) control essential gene regulatory pathways in plants and
      animals. Serving as guides in silencing complexes, miRNAs direct Argonaute
      proteins to specific target messenger RNAs to repress protein expression. The
      mature, 22-nucleotide (nt) miRNA is the product of multiple processing steps, and
      recent studies have uncovered factors that directly control the stability of the
      functional RNA form. Although alteration of miRNA levels has been linked to
      numerous disease states, the mechanisms responsible for stabilized or reduced
      miRNA expression have been largely elusive. The discovery of specific cis-acting
      modifications and trans-acting proteins that affect miRNA half-life reveals new
      elements that contribute to the homeostasis of these vital regulatory molecules.

PMID- 20051983
TI  - DNA resection in eukaryotes: deciding how to fix the break.
AB  - DNA double-strand breaks are repaired by different mechanisms, including
      homologous recombination and nonhomologous end-joining. DNA-end resection, the
      first step in recombination, is a key step that contributes to the choice of DSB
      repair. Resection, an evolutionarily conserved process that generates single
      stranded DNA, is linked to checkpoint activation and is critical for survival.
      Failure to regulate and execute this process results in defective recombination
      and can contribute to human disease. Here I review recent findings on the
      mechanisms of resection in eukaryotes, from yeast to vertebrates, provide
      insights into the regulatory strategies that control it, and highlight the
      consequences of both its impairment and its deregulation.

PMID- 20051984
TI  - Genetics of mammalian meiosis: regulation, dynamics and impact on fertility.
AB  - Meiosis is an essential stage in gamete formation in all sexually reproducing
      organisms. Studies of mutations in model organisms and of human haplotype
      patterns are leading to a clearer understanding of how meiosis has adapted from
      yeast to humans, the genes that control the dynamics of chromosomes during
      meiosis, and how meiosis is tied to gametic success. Genetic disruptions and
      meiotic errors have important roles in infertility and the aetiology of
      developmental defects, especially aneuploidy. An understanding of the regulation
      of meiosis, coupled with advances in genomics, may ultimately allow us to
      diagnose the causes of meiosis-based infertilities, more wisely apply assisted
      reproductive technologies, and derive functional germ cells.

PMID- 20051985
TI  - The molecular evolutionary basis of species formation.
AB  - All plant and animal species arise by speciation - the evolutionary splitting of
      one species into two reproductively incompatible species. But until recently our
      understanding of the molecular genetic details of speciation was slow in coming
      and largely limited to Drosophila species. Here, I review progress in determining
      the molecular identities and evolutionary histories of several new 'speciation
      genes' that cause hybrid dysfunction between species of yeast, flies, mice and
      plants. The new work suggests that, surprisingly, the first steps in the
      evolution of hybrid dysfunction are not necessarily adaptive.

PMID- 20051987
TI  - 2R or not 2R is not the question anymore.

PMID- 20051986
TI  - The evolution of gene duplications: classifying and distinguishing between
      models.
AB  - Gene duplications and their subsequent divergence play an important part in the
      evolution of novel gene functions. Several models for the emergence, maintenance
      and evolution of gene copies have been proposed. However, a clear consensus on
      how gene duplications are fixed and maintained in genomes is lacking. Here, we
      present a comprehensive classification of the models that are relevant to all
      stages of the evolution of gene duplications. Each model predicts a unique
      combination of evolutionary dynamics and functional properties. Setting out these
      predictions is an important step towards identifying the main mechanisms that are
      involved in the evolution of gene duplications.

PMID- 20051988
TI  - Piecemeal or big bangs: correlating the vertebrate evolution with proposed models
      of gene expansion events.

PMID- 20051989
TI  - Differential decay of parent-of-origin-specific genomic sharing in cystic
      fibrosis-affected sib pairs maps a paternally imprinted locus to 7q34.
AB  - Cystic fibrosis (CF) is a monogenic disease characterized by a high variability
      of disease severity and outcome that points to the role of environmental factors
      and modulating genes that shape the course of this multiorgan disease. We
      genotyped families of cystic fibrosis sib pairs homozygous for F508del-CFTR who
      represent extreme clinical phenotypes at informative microsatellite markers
      spanning a 38 Mb region between CFTR and 7qtel. Recombination events on both
      parental chromosomes were compared between siblings with concordant clinical
      phenotypes and siblings with discordant clinical phenotypes. Monitoring parent-of
      origin-specific decay of genomic sharing delineated a 2.9-Mb segment on 7q34 in
      which excess of recombination on paternal chromosomes in discordant pairs was
      observed compared with phenotypically concordant sibs. This 2.9-Mb core candidate
      region was enriched in imprinting-related elements such as predicted CCCTC
      binding factor consensus sites and CpG islands dense in repetitive elements.
      Moreover, allele frequencies at a microsatellite marker within the core candidate
      region differed significantly comparing mildly and severely affected cystic
      fibrosis sib pairs. The identification of this paternally imprinted locus on 7q34
      as a modulator of cystic fibrosis disease severity shows that imprinted elements
      can be identified by straightforward fine mapping of break points in sib pairs
      with informative contrasting phenotypes.

PMID- 20051990
TI  - Human Y chromosome haplogroup R-V88: a paternal genetic record of early mid
      Holocene trans-Saharan connections and the spread of Chadic languages.
AB  - Although human Y chromosomes belonging to haplogroup R1b are quite rare in
      Africa, being found mainly in Asia and Europe, a group of chromosomes within the
      paragroup R-P25(*) are found concentrated in the central-western part of the
      African continent, where they can be detected at frequencies as high as 95%.
      Phylogenetic evidence and coalescence time estimates suggest that R-P25(*)
      chromosomes (or their phylogenetic ancestor) may have been carried to Africa by
      an Asia-to-Africa back migration in prehistoric times. Here, we describe six new
      mutations that define the relationships among the African R-P25(*) Y chromosomes
      and between these African chromosomes and earlier reported R-P25 Eurasian sub
      lineages. The incorporation of these new mutations into a phylogeny of the R1b
      haplogroup led to the identification of a new clade (R1b1a or R-V88) encompassing
      all the African R-P25(*) and about half of the few European/west Asian R-P25(*)
      chromosomes. A worldwide phylogeographic analysis of the R1b haplogroup provided
      strong support to the Asia-to-Africa back-migration hypothesis. The analysis of
      the distribution of the R-V88 haplogroup in >1800 males from 69 African
      populations revealed a striking genetic contiguity between the Chadic-speaking
      peoples from the central Sahel and several other Afroasiatic-speaking groups from
      North Africa. The R-V88 coalescence time was estimated at 9.2-5.6 [corrected]
      kya, in the early mid Holocene. We suggest that R-V88 is a paternal genetic
      record of the proposed mid-Holocene migration of proto-Chadic Afroasiatic
      speakers through the Central Sahara into the Lake Chad Basin, and
      geomorphological evidence is consistent with this view.

PMID- 20051991
TI  - Frequent genetic differences between matched primary and metastatic breast cancer
      provide an approach to identification of biomarkers for disease progression.
AB  - Breast cancer is a major cause of morbidity and mortality in women and its
      metastatic spread is the principal reason behind the fatal outcome. Metastasis
      related research of breast cancer is however underdeveloped when compared with
      the abundant literature on primary tumors. We applied an unexplored approach
      comparing at high resolution the genomic profiles of primary tumors and
      synchronous axillary lymph node metastases from 13 patients with breast cancer.
      Overall, primary tumors displayed 20% higher number of aberrations than
      metastases. In all but two patients, we detected in total 157 statistically
      significant differences between primary lesions and matched metastases. We
      further observed differences that can be linked to metastatic disease and there
      was also an overlapping pattern of changes between different patients. Many of
      the differences described here have been previously linked to poor patient
      survival, suggesting that this is a viable approach toward finding biomarkers for
      disease progression and definition of new targets useful for development of
      anticancer drugs. Frequent genetic differences between primary tumors and
      metastases in breast cancer also question, at least to some extent, the role of
      primary tumors as a surrogate subject of study for the systemic disease.

PMID- 20051993
TI  - Fractal geometry in the nucleus.

PMID- 20051995
TI  - Traumatic optic neuropathy--to treat or not to treat?

PMID- 20051996
TI  - Transient cerebral cortex anaesthesia following peribulbar block.

PMID- 20051997
TI  - Central serous chorioretinopathy in a patient with congenital retinal
      macrovessel.

PMID- 20051998
TI  - Optic neuritis as an initial presentation of Wegener's granulomatosis.

PMID- 20051999
TI  - Management of endogenous cryptococcal endophthalmitis with voriconazole.

PMID- 20052000
TI  - A case of superficial corneal tattooing for glare after trabeculectomy.

PMID- 20052001
TI  - Trichomegaly secondary to erlotinib.

PMID- 20052002
TI  - [Breast cancer discovered from choroidal metastasis: Apropos of a case and review
      of the literature].

PMID- 20052007
TI  - Cyanobacterial toxins and liver disease.
AB  - Blue-green algae, also known as cyanobacteria, produce a variety of toxins, some
      of which have been implicated in the pathogenesis of severe and potentially life
      threatening diseases in humans. As the growth of cyanobacteria within freshwater
      lakes increases worldwide, it is important to review our present understanding of
      their toxicity and potential carcinogenicity to gain insight into how these
      organisms impact human health. This review addresses each of these topics, with
      special emphasis given to cyanobacterial hepatotoxins within freshwater
      environments.

PMID- 20052008
TI  - Protein kinase inhibition differentially regulates organic cation transport.
AB  - Previous studies showed that amantadine transport increased while
      tetraethylammonium (TEA) transport decreased in kidney tissue from diabetic rats.
      Changes in transport activity were reversed by exogenous insulin. We hypothesized
      that this difference in transport regulation is due to differential regulation of
      different transport systems. Native human embryonic kidney cortex cells (HEK293
      cell line) and rat organic cation transporter (rOCT)-transfected cells were used
      to test the hypothesis. In support of differential regulation, short-term glucose
      starvation stimulated amantadine transport and inhibited TEA transport, but the
      effect was bicarbonate-modulated only for amantadine. cAMP analogues inhibited
      TEA transport while stimulating amantadine transport. This effect was additive to
      the effect of insulin, and the presence of bicarbonate affected the extent of the
      change. Our findings indicated that regulation of rOCT 1 and 2 was mediated by
      transmembrane adenylyl cyclase, and regulation of amantadine transport was
      mediated by soluble adenylyl cyclase, suggesting that intracellular microdomains
      of cAMP may be important in determining overall cellular transport for organic
      cations. Soluble adenylyl cyclase activity is known to be modulated by
      bicarbonate and lactate. These observations support our hypothesis and reconcile
      our previous studies demonstrating increased transport affinity for amantadine in
      the presence of bicarbonate and decreased transport affinity in the presence of
      lactate.

PMID- 20052009
TI  - Targeted production of proprotein convertase PC1 enhances mammary development and
      tumorigenesis in transgenic mice.
AB  - Elevated production of proprotein convertases (PCs), proteolytic enzymes that
      posttranslationally modify the biological activities of diverse groups of
      cellular proteins, is a common occurrence in human breast carcinomas. A
      transgenic mouse model was developed to gain insight into the significance of PC
      production in breast development and neoplasia. Mammary epithelium-specific and
      early expression of PC1 was targeted by the use of the mouse mammary tumor virus
      promoter/enhancer. Whole-mount examinations revealed that the mammary glands of
      83-day-old virgin PC1 transgenic mice exhibited an accelerated lobuloalveolar
      development compared with that of age-matched wild-type mice (p < 0.001). This
      phenotypic change was accompanied by extensive alterations in gene expression
      assessed by gene expression microarray analyses. Pathway analysis of PC1-induced
      alterations in gene expression has revealed possible mechanism of action of PC1
      in the mammary gland. PC1 expression alone, however, did not promote spontaneous
      mammary tumorigenesis in the transgenic mice. PC1 transgene expression resulted
      in a significantly higher incidence (p = 0.008) and accelerated growth (p =
      0.023) of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas.
      The present study therefore shows that PC1 expression can promote normal and
      neoplastic mammary development and growth and suggests that proprotein
      convertases may be important etiological factors in human breast neoplasia.

PMID- 20052010
TI  - Tail suspension increases energy expenditure independently of the melanocortin
      system in mice.
AB  - Space travelers experience anorexia and body weight loss in a microgravity
      environment, and microgravity-like situations cause changes in hypothalamic
      activity. Hypothalamic melanocortins play a critical role in the regulation of
      metabolism. Therefore, we hypothesized that microgravity affects metabolism
      through alterations in specific hypothalamic signaling pathways, including
      melanocortin signaling. To address this hypothesis, the microgravity-like
      situation was produced by an antiorthostatic tail suspension in wild-type and
      agouti mice, and the effect of tail suspension on energy expenditure and
      hypothalamic gene expression was examined. Energy expenditure was measured using
      indirect calorimetry before and during the tail suspension protocol. Hypothalamic
      tissues were collected for gene expression analysis at the end of the 3 h tail
      suspension period. Tail suspension significantly increased oxygen consumption,
      carbon dioxide production, and heat production in wild-type mice. Tail suspension
      induced increases in energy expenditure were not attenuated in agouti mice.
      Although tail suspension did not alter hypothalamic proopiomelanocortin (POMC)
      and agouti-related protein (AGRP) mRNA levels, it significantly increased
      hypothalamic interleukin 6 (Il-6) mRNA levels. These data are consistent with the
      hypothesis that microgravity increases energy expenditure and suggest that these
      effects are mediated through hypothalamic signaling pathways that are independent
      of melanocortins, but possibly used by Il-6.

PMID- 20052011
TI  - N-methyl-D-aspartate-evoked adenosine and inosine release from neurons requires
      extracellular calcium.
AB  - The nucleoside adenosine (ADO) is a neuromodulator in brain. ADO and its
      metabolite inosine (INO) have been shown to increase cell viability in stroke
      models. During ischemia, extracellular levels of both ADO and INO are increased.
      In this study, we treated rat cortical neurons with N-methyl-D-aspartate (NMDA)
      to initiate excitotoxicity and then investigated the mechanisms of ADO and INO
      release. NMDA induced a significant increase in ADO and INO production. The
      effect of NMDA receptor antagonists on NMDA-evoked ADO and INO release was
      examined. MK-801 (1 micromol/L), a potent antagonist that lacks receptor subunit
      selectivity, completely blocked evoked release of both ADO and INO. Memantine (10
      micromol/L), a lower affinity antagonist that also lacks subunit selectivity,
      blocked INO, but not ADO, release. Ifenprodil (10 micromol/L), an inhibitor
      selective for NMDA receptors containing the NR2B subunit, completely blocked
      evoked ADO and INO release. NVP-AAM077 (NVP, 0.4 micromol/L), an inhibitor
      selective for NMDA receptors containing the NR2A subunit, did not significantly
      block evoked release of either ADO or INO. Removal of extracellular Ca2+
      abolished NMDA-evoked release of both ADO and INO. BAPTA (25 micromol/L), which
      chelates intracellular Ca2+, had no significant effect on either ADO or INO
      release unless extracellular Ca2+ was also removed. Inhibitors of Ca2+/calmodulin
      dependent protein kinase II (CaMKII) prevented NMDA-evoked ADO and INO release
      and decreased nucleoside transporter function. These data indicate that NMDA
      evoked ADO and INO release is dependent on subunit composition of NMDA receptors.
      As well, NMDA-evoked ADO and INO release requires nucleoside transporters and
      extracellular Ca2+ and is enhanced by activation of CaMKII.

PMID- 20052012
TI  - Generation and initial characterization of the prolactin-inducible protein (PIP)
      null mouse: accompanying global changes in gene expression in the submandibular
      gland.
AB  - The human prolactin-inducible protein/gross cystic disease fluid protein-15
      (hPIP/GCDFP-15) is a secretory glycoprotein found primarily in apocrine tissues
      including the breast and salivary glands. With largely unknown functions, PIP has
      been implicated in breast cancer and metastasis, host defense processes and T
      lymphocyte apoptosis. To begin to address PIP function in vivo, we generated the
      PIP null mouse (Pip-/-). Additionally, to determine the effect of the loss of PIP
      on gene expression and to gain insight into some of the molecular mechanisms
      underlying PIP function, microarray analysis of the submandibular gland was also
      undertaken. Pip-/- mice developed normally with no overt differences in behaviour
      or gross morphology and were fertile. However, histological examination of 3
      month-old Pip-/- mice sometimes showed enlarged submandibular lymph nodes,
      lymphocytic aggregations within the prostate lobes, and enlarged medulla in the
      thymus. Functional analysis of gene expression revealed sets of multiple
      differentially expressed genes associated with cell death and survival, lipid
      metabolism, inflammation, immune disease, and cancer, as a consequence of mPIP
      abrogation. Taken together, these studies lend support to an immunomodulatory
      role for PIP in vivo and provide further insights into potentially novel
      signaling pathways and regulatory networks for PIP.

PMID- 20052013
TI  - Obesity, syndrome X, and diabetes: the role of HISS-dependent insulin resistance
      altered by sucrose, an antioxidant cocktail, and age.
AB  - Absence of meal-induced insulin sensitization (AMIS) results in a predictable
      progression of dysfunctions, including postprandial hyperglycemia, compensatory
      hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and
      obesity, progressing to syndrome X and diabetes. To test the 'AMIS syndrome'
      hypothesis we used 3 known means of producing graded and progressive changes in
      meal-induced insulin sensitization in rats. We used an aging model (9, 26, and 52
      weeks), associated with a slow development of AMIS; a low-dose sucrose supplement
      model to accelerate the development of AMIS; and an antioxidant cocktail (S
      adenosylmethionine, vitamin E, and vitamin C) to protect against the effect of
      the sucrose on meal-induced insulin sensitization. Adiposity was assessed from
      weighed regional fat masses and bioelectrical impedance. AMIS developed with age,
      was increased by sucrose supplementation, and was inhibited by the antioxidant
      cocktail. AMIS correlated with postprandial hyperglycemia, hyperinsulinemia,
      hyperlipidemia, and with adiposity (r2 = 0.7-0.8) regardless of age or nutrient
      status. The range of degrees of AMIS, established over time with these models,
      afforded the tool with which to test the AMIS syndrome and further the argument
      that AMIS is the first metabolic defect that cumulatively leads to a predictable
      series of homeostatic disturbances and dysfunctions, including obesity and type 2
      diabetes.

PMID- 20052014
TI  - Neuregulin beta1 enhances peak glutamate-induced intracellular calcium levels
      through endoplasmic reticulum calcium release in cultured hippocampal neurons.
AB  - Modulation of intracellular free calcium levels is the primary second messenger
      system of the neuronal glutamatergic system, playing a role in regulation of all
      major cellular processes. The protein neuregulin (NRG) beta1 acts as an
      extracellular signaling ligand in neurons, rapidly regulating currents through
      ionotropic glutamate receptors. The effect NRG may have on glutamate-induced
      changes in intracellular free calcium concentrations has not been examined,
      however. In this study, cultured embryonic rat hippocampal neurons were treated
      with NRGbeta1 to determine a possible effect on glutamate-induced intracellular
      calcium levels. Long-term (24 h), but not short-term (1 h), incubation with
      NRGbeta1 resulted in a significantly greater glutamate-mediated acute peak
      elevation of intracellular calcium levels than occurred in vehicle-treated
      neurons. Long-term NRGbeta1 incubation significantly enhanced calcium increase
      induced by specific stimulation of metabotropic glutamate receptors, but did not
      significantly alter the N-methyl D-aspartate (NMDA)- or KCl-induced calcium
      increase and paradoxically decreased the effect of alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) treatment on intracellular calcium. Metabotropic
      glutamate receptors cause increased intracellular free calcium via release of
      calcium from intracellular stores; thus this system was examined in more detail.
      NRGbeta1 treatment significantly (greater than 2-fold) enhanced calcium release
      from endoplasmic reticulum stores after stimulation of ryanodine receptors with
      caffeine, but did not significantly increase calcium release from endoplasmic
      reticulum mediated by inositol trisphosphate (IP3) receptors. In addition,
      ryanodine receptor inhibition with ruthenium red prevented the glutamate-induced
      increase in intracellular calcium levels in NRGbeta1-treated neurons. These data
      show that long-term NRGbeta1 treatment can enhance glutamate-induced peak
      intracellular calcium levels through metabotropic glutamate receptor activation
      by increasing endoplasmic reticulum calcium release through ryanodine receptors.

PMID- 20052043
TI  - Quantitative study of single molecule location estimation techniques.
AB  - Estimating the location of single molecules from microscopy images is a key step
      in many quantitative single molecule data analysis techniques. Different
      algorithms have been advocated for the fitting of single molecule data,
      particularly the nonlinear least squares and maximum likelihood estimators.
      Comparisons were carried out to assess the performance of these two algorithms in
      different scenarios. Our results show that both estimators, on average, are able
      to recover the true location of the single molecule in all scenarios we examined.
      However, in the absence of modeling inaccuracies and low noise levels, the
      maximum likelihood estimator is more accurate than the nonlinear least squares
      estimator, as measured by the standard deviations of its estimates, and attains
      the best possible accuracy achievable for the sets of imaging and experimental
      conditions that were tested. Although neither algorithm is consistently superior
      to the other in the presence of modeling inaccuracies or misspecifications, the
      maximum likelihood algorithm emerges as a robust estimator producing results with
      consistent accuracy across various model mismatches and misspecifications. At
      high noise levels, relative to the signal from the point source, neither
      algorithm has a clear accuracy advantage over the other. Comparisons were also
      carried out for two localization accuracy measures derived previously. Software
      packages with user-friendly graphical interfaces developed for single molecule
      location estimation (EstimationTool) and limit of the localization accuracy
      calculations (FandPLimitTool) are also discussed.

PMID- 20052044
TI  - Determination of topological charges of polychromatic optical vortices.
AB  - We introduce a simple, single beam method for determination of the topological
      charge of polychromatic optical vortices. It is based on astigmatic
      transformation of singular optical beams, where the intensity pattern of a vortex
      beam acquires a form of dark stripes in the focal plane of a cylindrical lens.
      The number of the dark stripes is equal to the modulus of the vortex topological
      charge, while the stripe tilt indicates the charge sign. We demonstrate
      experimentally the effectiveness of this technique by revealing complex
      topological structure of polychromatic singular beams.

PMID- 20052045
TI  - Dynamic switching characteristics of InGaAsP/InP multimode interference optical
      waveguide switch.
AB  - Multimode interference (MMI) waveguide switches show promise for switch in
      optical packet switching (OPS). In this work, we fabricated 1 x 4 InGaAsP/InP MMI
      waveguide switch device which consists of a 1 x 4 MMI splitter, 4 equally spaced
      single-mode waveguides with phase shifters, and a 4 x 4 MMI combiner. Good
      crosstalk and extinction ratio of -14.47 dB and 23.39 dB, respectively, are
      obtained. In addition, we experimentally demonstrate dynamic switching, and the
      rise and fall time of 1.4 ns and 1.2 ns, respectively, are obtained.

PMID- 20052046
TI  - Generating superpositions of higher-order Bessel beams.
AB  - We report the first experimental generation of the superposition of higher-order
      Bessel beams, by means of a spatial light modulator (SLM) and a ring slit
      aperture. We present illuminating a ring slit aperture with light which has an
      azimuthal phase dependence, such that the field produced is a superposition of
      two or more higher-order Bessel beams. The experimentally produced fields are in
      good agreement with those calculated theoretically. The significance of these
      fields is that even though one is able to generate fields which carry zero
      orbital angular momentum, a rotation in the field's intensity profile as it
      propagates is observed.

PMID- 20052047
TI  - Noninvasive monitoring of tissue hemoglobin using UV-VIS diffuse reflectance
      spectroscopy: a pilot study.
AB  - We conducted a pilot study on 10 patients undergoing general surgery to test the
      feasibility of diffuse reflectance spectroscopy in the visible wavelength range
      as a noninvasive monitoring tool for blood loss during surgery. Ratios of raw
      diffuse reflectance at wavelength pairs were tested as a first-pass for
      estimating hemoglobin concentration. Ratios can be calculated easily and rapidly
      with limited post-processing, and so this can be considered a near real-time
      monitoring device. We found the best hemoglobin correlations were when ratios at
      isosbestic points of oxy- and deoxyhemoglobin were used, specifically 529/500 nm.
      Baseline subtraction improved correlations, specifically at 520/509 nm. These
      results demonstrate proof-of-concept for the ability of this noninvasive device
      to monitor hemoglobin concentration changes due to surgical blood loss. The
      529/500 nm ratio also appears to account for variations in probe pressure, as
      determined from measurements on two volunteers.

PMID- 20052048
TI  - A near-perfect invisibility cloak constructed with homogeneous materials.
AB  - A near-perfect, non-singular cylindrical invisibility cloak with diamond cross
      section is achieved by a two-step coordinate transformation. A small line segment
      is stretched and then blown up into a diamond space, and finally the cloak
      consisting of four kinds and eight blocks of homogeneous transformation media is
      obtained. Numerical simulations confirm the well performance of the cloak. The
      operation bandwidth of the cloak is also investigated. Our scheme is promising to
      create a simple and well-performed cloak in practice.

PMID- 20052049
TI  - Fast vertical alignment mode with continuous multi-domains for a liquid crystal
      display.
AB  - We proposed a fast liquid crystal display (LCD) in a vertical alignment (VA) mode
      with continuous multi-domains for wide-viewing characteristics. The fast VA LCD
      was fabricated by the mixed vertical alignment layer with UV curable reactive
      mesogen (RM) polymer memorizing the switching directions of the LC molecules. The
      wide-viewing and fast response characteristics were obtained by axially symmetric
      switching directions and the memorization of them without any specific electrode
      patterns or surface structures.

PMID- 20052050
TI  - Implicitly causality enforced solution of multidimensional transient photon
      transport equation.
AB  - A novel method for solving the multidimensional transient photon transport
      equation for laser pulse propagation in biological tissue is presented. A
      Laguerre expansion is used to represent the time dependency of the incident short
      pulse. Owing to the intrinsic causal nature of Laguerre functions, our technique
      automatically always preserve the causality constrains of the transient signal.
      This expansion of the radiance using a Laguerre basis transforms the transient
      photon transport equation to the steady state version. The resulting equations
      are solved using the discrete ordinates method, using a finite volume approach.
      Therefore, our method enables one to handle general anisotropic, inhomogeneous
      media using a single formulation but with an added degree of flexibility owing to
      the ability to invoke higher-order approximations of discrete ordinate quadrature
      sets. Therefore, compared with existing strategies, this method offers the
      advantage of representing the intensity with a high accuracy thus minimizing
      numerical dispersion and false propagation errors. The application of the method
      to one, two and three dimensional geometries is provided.

PMID- 20052051
TI  - Ultra-fast switching of light by absorption saturation in vacuum ultra-violet
      region.
AB  - Advances in free electron lasers producing high energy photons [Nat. Photonics
      2(9), 555-559 (2008)] are expected to open up a new science of nonlinear optics
      of high energy photons. Specifically, lasers of photon energy higher than the
      plasma frequency of a metal can show new interaction features because they can
      penetrate deeply into metals without strong reflection. Here we show the
      observation of ultra-fast switching of vacuum ultra-violet (VUV) light caused by
      saturable absorption of a solid metal target. A strong gating is observed at
      energy fluences above 6J/cm2 at wavelength of 51 nm with tin metal thin layers.
      The ratio of the transmission at high intensity to low intensity is typically
      greater than 100:1. This means we can design new nonlinear photonic devices such
      as auto-correlator and pulse slicer for the VUV region.

PMID- 20052052
TI  - LED beam shaping lens based on the near-field illumination.
AB  - This paper presents a novel method in near-field beam shaping based on the
      precise optical modeling of a gallium nitride light-emitting diode (GaN LED). A
      Monte Carlo ray tracing simulation has been utilized to calculate the spatial
      photon distribution near the LED's top. By analyzing the ray data in near-field,
      the miniaturized lens profile is created and machined with aspherical surfaces
      and total internal reflection (TIR) Fresnel facets. The prototype lens reduce the
      viewing angle of the LED from 150 degrees to 17.5 degrees at full width half
      maximum (FWHM) while increasing the peak luminous intensity 10 times. The array
      of proposed lens with CSP LEDs exhibits feasibility of ultra thin uniform
      illumination in near-field.

PMID- 20052053
TI  - Optical bistable devices based on guided-mode resonance in slab waveguide
      gratings.
AB  - We investigate properties of nonlinear resonant gratings with emphasis on optical
      bistability. Slab waveguide gratings with various quality factors are designed
      and their characteristics analyzed with a finite-difference time-domain method.
      Considerable field enhancements are observed in the gratings and the performance
      compares favorably with metallic bistable devices. Bistability based on coupled
      gratings is also treated. Mechanically controllable switching intensity realized
      by varying a gap distance between two gratings is demonstrated. Resonant
      nonlinear elements in this work may find applications in all-optical information
      processing and optical switching, and our investigation on the dependence of the
      normalized switching intensity and the response time on quality factor will
      provide a general guide line for grating-based bistable device design.

PMID- 20052054
TI  - 7-cell core hollow-core photonic crystal fibers with low loss in the spectral
      region around 2 microm.
AB  - Several 7 cell core hollow-core photonic crystal fibers with bandgaps in the
      spectral range of 1.4 microm to 2.3 microm have been fabricated. The transmission
      loss follows the approximately lambda(-3) dependency previously reported, with a
      minimum measured loss of 9.5 dB/km at 1.99 microm. One fiber with a transmission
      loss of 26 dB/km at 2.3 microm is reported, which is significantly lower than the
      transmission loss of solid silica fibers at this wavelength.

PMID- 20052055
TI  - Quantitative modeling of coupling-induced resonance frequency shift in microring
      resonators.
AB  - We present a detailed study on the behavior of coupling-induced resonance
      frequency shift (CIFS) in dielectric microring resonators. CIFS is related to the
      phase responses of the coupling region of the resonator coupling structure, which
      are examined for various geometries through rigorous numerical simulations. Based
      on the simulation results, a model for the phase responses of the coupling
      structure is presented and verified to agree with the simulation results well, in
      which the first-order coupled mode theory (CMT) is extended to second order, and
      the important contributions from the inevitable bent part of practical resonators
      are included. This model helps increase the understanding of the CIFS behavior
      and makes the calculation of CIFS for practical applications without full
      numerical simulations possible.

PMID- 20052056
TI  - Investigation of stress induced by CO2 laser processing of fused silica optics
      for laser damage growth mitigation.
AB  - Laser damage mitigation' is a process developed to prevent the growth of
      nanosecond laser-initiated damage sites under successive irradiation. It consists
      of re-fusing the damage area with a CO2 laser. In this paper we investigate the
      stress field created around mitigated sites which could have an influence on the
      efficiency of the process. A numerical model of CO2 laser interaction with fused
      silica is developed. It takes into account laser energy absorption, heat
      transfer, thermally induced stress and birefringence. Residual stress near
      mitigated sites in fused silica samples is characterized with specific
      photoelastic methods and theoretical data are compared to experiments. The stress
      distribution and quantitative values of stress levels are obtained for sites
      treated with the CO2 laser in various conditions of energy deposition (beam size,
      pulse duration, incident power). The results provided evidence that the presence
      of birefringence/residual stress around the mitigated sites has an effect on
      their laser damage resistance.

PMID- 20052057
TI  - Fast and slow light in optical fibers through tilted fiber Bragg gratings.
AB  - In this paper, slow and fast light in optical fiber through tilted fiber Bragg
      grating (TFBG) are reported. The experimental results show the capability of
      TFBGs to enable group velocity control of an optical pulse in optical fiber, due
      to the anomalous dispersion features induced by the coupling between the
      propagating core mode and each counter-propagating coupling cladding mode. In
      particular, superluminal propagation of a pulse train has been observed at
      optical communication wavelengths with time advancements in the picoseconds time
      scale in 1cm long TFBG and group velocity as large as about two times the speed
      of light in optical fiber (approximately 1.3 x c0). Very good agreement has been
      obtained comparing the measured group delay of the TFBG with the one retrieved
      from the amplitude response through Hilbert transform. Finally, tunable slow and
      fast light has also been reported, demonstrating the possibility to control the
      group velocity at single wavelength through both fluidic and thermal actuation.

PMID- 20052058
TI  - Design and optimization of a novel surface plasmon resonance biosensor based on
      Otto configuration.
AB  - A theoretical study on a novel planar waveguide surface Plasmon Biosensor is
      presented in this paper. The proposed biosensor has a configuration similar to
      the Otto excitation mechanism for surface Plasmon polaritons. The performance of
      the device with respect to key system parameters such as gap-width and device
      length is investigated using an eigenmode solver with perfectly matched layers
      (PML). Device resolution of 2.3 x 10(-6) RIU has been demonstrated for an aqueous
      analyte.

PMID- 20052059
TI  - Mask-less ultraviolet photolithography based on CMOS-driven micro-pixel light
      emitting diodes.
AB  - We report on an approach to ultraviolet (UV) photolithography and direct writing
      where both the exposure pattern and dose are determined by a complementary metal
      oxide semiconductor (CMOS) controlled micro-pixellated light emitting diode
      array. The 370 nm UV light from a demonstrator 8 x 8 gallium nitride micro-pixel
      LED is projected onto photoresist covered substrates using two back-to-back
      microscope objectives, allowing controlled demagnification. In the present setup,
      the system is capable of delivering up to 8.8 W/cm2 per imaged pixel in circular
      spots of diameter approximately 8 microm. We show example structures written in
      positive as well as in negative photoresist.

PMID- 20052060
TI  - Phosphor converted LEDs with omni-directional-reflector coating.
AB  - A packaging scheme utilizing omni-directional reflective (ODR) optical coating is
      described to enhance the light extraction of near UV excited, phosphor-converted
      LEDs. A simple 1D model was developed to analyze the spectra of the extracted
      light measured with an integration-sphere as a function of phosphor layer
      concentration and thickness. Quantitative determination of the absorption
      coefficients at the pump and fluorescent light wavelength along with the
      conversion coefficient of phosphors were obtained. The reflection of the ODR film
      and the back reflector are also characterized. These parameters are then used for
      efficiency optimization of the present packaging scheme. A maximum enhancement of
      40% can be expected with the materials and the configuration used in the present
      work.

PMID- 20052062
TI  - Tunable guided-mode resonances in coupled gratings.
AB  - We present a rigorous numerical analysis on tunable characteristics of guided
      mode resonances (GMRs) in coupled gratings. Two schemes of strong and negligible
      evanescent coupling of guided modes are treated. Both show wide range tunability.
      In the case of strong evanescent coupling, independent control of the center
      wavelength and the linwidth of the resonance is obtained via variations of a gap
      size between the gratings and lateral alignment conditions. We believe that this
      characteristic will provide a useful means to realize a tunable filter in
      conjunction with micro/nano-electromechanical system technologies. We also
      present a generalized theoretical analysis on the tunable characteristics of the
      GMRs in coupled gratings, which is qualitatively in good agreement with the
      numerical analysis.

PMID- 20052061
TI  - Thermal lens study in diode pumped Ng- and Np-cut Nd:KGd(WO4)2 laser crystals.
AB  - A comparative study of thermal lensing effect in diode laser pumped Ng- and Np
      cut Nd:KGd(WO4)2 (KGW) laser crystals was performed for laser emission polarized
      along the principle refractive axis, Nm. The thermal lens in the Ng-cut Nd: KGW
      was found to be weakly astigmatic with a positive refractive power for both the
      Nm- and Np-directions. For Np -cut Nd:KGW, strong astigmatism was observed and
      the refractive powers in the Ng- and Nm-directions had opposing signs. The degree
      of astigmatism was found to be considerably weaker for the Ng-cut Nd:KGW in
      comparison with the Np-cut one: 0.35 dptr/(W/cm2) and 2.85 dptr/(W/cm2),
      respectively. The ratio of the thermal lens refractive powers in the planes
      parallel and perpendicular to the laser emission polarisation were measured as
      +1.4 and -0.425 for Ng- and Np-cut Nd:KGW respectively.

PMID- 20052064
TI  - Compactly packaged superconducting nanowire single-photon detector with an
      optical cavity for multichannel system.
AB  - We developed superconducting nanowire single-photon detectors with an optical
      cavity (OC-SNSPDs) for multichannel systems. For efficient coupling, the devices
      were installed in compact fiber-coupled packages after their substrate thickness
      was reduced from 400 to 45 microm. The measured detection efficiency (DE)
      measurement at different substrate thicknesses and the estimation of optical
      coupling efficiency indicated that approximately 98% of the input light beam
      could be radiated on a 15 x 15 microm2 nanowire area from behind the substrate.
      The DEs of a NbN OC-SNSPD system were observed to be 9.5% and 25% at 1550 nm and
      1310 nm, respectively (dark-count rate: 100 c/s).

PMID- 20052065
TI  - Generation of pretilt angles of liquid crystals on cinnamate-based photoalignment
      layer by a simple directional peel-off process.
AB  - As an alternative to the rubbing method, the photoalignment method has been
      extensively developed for liquid crystal displays owing to its various advantages
      including the absence of any contamination problems, feasibility of multi-domain
      structure formation, and low temperature processing capability. However,
      cinnamate-based photo-reactive materials that are widely used in photoalignment
      suffer from several limitations including low pretilt angle and limited control
      of tilted-up direction of the liquid crystals compared to that of the rubbing
      process. In this work, we demonstrate a simple and convenient method to generate
      the pretilt angle, compared to that achieved via the rubbing method, by means of
      a simple directional peel-off process using a photo-reactive cinnamate oligomer
      having flexible molecular chain.

PMID- 20052066
TI  - Dual-axis beam correction for an array of single-mode diode laser emitters using
      a laser-written custom phase-plate.
AB  - A single optical component for a diode laser bar combines fast-axis smile and
      lens error correction with slow-axis collimation. Produced by laser
      machining/polishing, it provides 0.9 mm focal length, 200 microm pitch slow-axis
      collimation on the same surface that corrects fast-axis errors. Custom
      fabrication enables fill-factor optimization for the 49 single-mode beams and
      gives parallel collimation with rms pointing errors of 3% and 6% of the far-field
      divergence for the fast- and slow-axis array respectively. Sub-micron pitch
      mismatch between the slow-axis lens and emitter arrays, and beam pointing changes
      by thermal expansion of the laser bar are detected.

PMID- 20052067
TI  - Third-harmonic generation from arrays of sub-wavelength metal apertures.
AB  - We measure third-harmonic generation (THG) from arrays of sub-wavelength metal
      apertures in transmission using fundamental input at 800 nm. Samples with
      different aperture spacings, sizes, and shapes are used. Strong angular
      dependence of THG is observed, with maxima located at incidence angles
      corresponding to extraordinary optical transmission (EOT) for the fundamental. We
      demonstrate an anomalous scaling of TH intensity with aperture size, where at
      different EOT peaks, the TH may either increase or decrease with aperture size.
      The aperture shape is also shown to have a strong effect on TH output.

PMID- 20052068
TI  - Photon pair generation in birefringent optical fibers.
AB  - We study both experimentally and theoretically the generation of photon pairs by
      spontaneous four-wave mixing (SFWM) in standard birefringent optical fibers. The
      ability to produce a range of two-photon spectral states, from highly correlated
      (entangled) to completely factorable, by means of cross-polarized birefringent
      phase matching, is explored. A simple model is developed to predict the spectral
      state of the photon pair which shows how this can be adjusted by choosing the
      appropriate pump bandwidth, fiber length and birefringence. Spontaneous Raman
      scattering is modeled to determine the tradeoff between SFWM and background Raman
      noise, and the predicted results are shown to agree with experimental data.

PMID- 20052069
TI  - Hybrid long-range surface plasmon-polariton modes with tight field confinement
      guided by asymmetrical waveguides.
AB  - A finite width dielectric-metal-dielectric (DMD) waveguide placed on a substrate
      is numerically investigated near the telecom wavelength lambda = 1550 nm by the
      finite element method. With proper waveguide sizes, the asymmetrical DMD
      waveguide can support hybrid long-range surface plasmon-polariton modes which
      have tight field confinement (approximately 700 nm) and long propagation lengths
      (L> 300 microm) simultaneously. Compact plasmonic waveguide-ring resonators
      (WRRs) based on such asymmetrical DMD waveguide show high quality factors
      compared with dielectric-loaded surface plasmon-polariton, channel plasmon
      polariton, plasmonic whispering-gallery microcavity, and pure dielectric
      waveguide cases.

PMID- 20052070
TI  - Observation of optical azimuthons.
AB  - We observe experimentally optical azimuthons, a generic class of ring-shaped
      localised spiralling beams with azimuthal modulation, carrying phase dislocation
      in self-focusing nonlinear media. We observe three- and four-lobe azimuthons in
      87Rb vapours and demonstrate their anomalous rotation controlled by the input
      phase distribution.

PMID- 20052071
TI  - Many-element coupled-resonator optical waveguides using gapless-coupled microdisk
      resonators.
AB  - We report silicon photonic many-element coupled-resonator optical waveguides
      (CROWs) using microspiral and double-notch-shaped microdisk resonators. Such
      microresonators enable gapless inter-cavity coupling via seamlessly jointed sub
      micrometer-sized notches. Our experiments reveal CROW transmission spectra using
      up to 101 gaplessly coupled microdisk resonators. We estimate from the
      transmission measurements an insertion loss of approximately 0.11-approximately
      0.24 dB/disk within the transmission bands. We show high-order filtering
      performance with maximum 3-dB linewidth of approximately 2.5 nm and measurement
      limited side-mode suppression ratio of approximately 30 dB. The demonstrated
      maximum optical delay from a 101-element 0.4-microm-notch CROW is approximately
      70 ps at the transmission band center and approximately 110 ps at the sideband.

PMID- 20052072
TI  - The long-term evolution of D2+ nuclear wave-packet with interaction of intense
      femtosecond laser pulse.
AB  - We investigate the long-term evolution of D2+ nuclear wave-packet after
      interacting with a 5 fs, 800 nm laser pulse at an intensity of 0.5 x 10(14)
      W/cm2. The nuclear wave-packet evolves in field-free condition for very long time
      after the laser pulse. The collapse and revival of nuclear wave-packet is
      studied. The scale of the classical time (approximately 25 fs), the revival time
      (approximately 580 fs) and the super-revival time (approximately 12 ps) are
      determined from the simulation as well as the calculation. The constituents of
      long-standing nuclear wave-packet are also analyzed.

PMID- 20052073
TI  - Power and wavelength polarization bistability with very wide hysteresis cycles in
      a 1550 nm-VCSEL subject to orthogonal optical injection.
AB  - We have measured optical power and wavelength polarization bistability in a 1550
      nm-Vertical Cavity Surface-Emitting Laser (VCSEL) subject to orthogonally
      polarized optical injection into the orthogonal polarization of the fundamental
      transverse mode. Optical bistability with very wide hysteresis cycles, up to four
      times wider than previously reported results has been measured for both the
      optical power and wavelength domain. We also report the experimental observation
      of three different shapes of polarization bistability, anticlockwise, clockwise
      and X-Shape bistability, all of them with wide hysteresis cycles. This rich
      variety of behaviour at the important wavelength of 1550 nm offers promise for
      the use of VCSELs for all-optical signal processing and optical switching/routing
      applications.

PMID- 20052074
TI  - Performance-enhanced superluminescent diode with surface plasmon waveguide.
AB  - Super luminescent Diode (SLD) with a new structure is proposed in which light is
      guided by surface plasmon waveguide (SPWG) rather than by the conventional
      dielectric waveguide. This results in a great increase of the spontaneous
      emission coupling. Other parameters important to the device operation such as the
      confinement factor, waveguide loss and waveguide facets reflectivities are also
      considered. It is shown that the new design outperforms the conventional ones
      using dielectric waveguides in both the output power and optical spectral width.

PMID- 20052075
TI  - Effect of retardation on localized surface plasmon resonances in a metallic
      nanorod.
AB  - The localized surface plasmon resonances in a metallic nanorod are determined
      using the "electrostatic approximation" and by a finite-difference time-domain
      numerical solution of Maxwell's equations. The difference between the two methods
      is related to the effects of re-radiation, or retardation, which is not included
      in the electrostatic formulation. It is shown that high-order modes in a metallic
      nanorod can be modeled by both methods, even beyond the point where the
      electrostatic method is supposed to fail. This suggests that the simple
      analytical expressions derived from the electrostatic approximation are valid for
      describing the large range of resonant modes associated with metallic
      nanoparticles, including dark modes.

PMID- 20052076
TI  - Cathodoluminescent spectroscopic imaging of surface plasmon polaritons in a 1
      dimensional plasmonic crystal.
AB  - Angle-resolved measurements on a cathodoluminescence (CL) detection system
      equipped with a 200 keV transmission electron microscope were performed on a 1
      dimensional silver grating. The dispersion curves of surface plasmon polaritons
      (SPPs) on the grating were derived from the angle-resolved CL spectra, and
      patterns of SPP standing waves at the plasmonic band edge were directly observed.

PMID- 20052077
TI  - Interference from a nonlocal double-slit through one-photon process.
AB  - In this paper, we report an interference experiment in which a spatially
      incoherent light source illuminates two spatially separated apertures, whose
      superposition at the same place forms a double-slit. The experimental result
      exhibits a well-defined interference fringe solely through intensity
      measurements, in agreement with the theoretical analysis by means of the first
      order spatial interference of the incoherent light. Consequently, the nonlocal
      double-slit interference with thermal light should be attributed to the first
      order spatial correlation of incoherent field.

PMID- 20052078
TI  - 150 W highly-efficient Raman fiber laser.
AB  - We report a more than 150 W spectrally-clean continuous wave Raman fiber laser at
      1120 nm with an optical efficiency of 85%. A approximately 30 m standard single
      mode silica fiber is used as Raman gain fiber to avoid second Stokes emission. A
      spectrally asymmetric resonator (in the sense of mirror reflection bandwidth)
      with usual fiber Bragg gratings is designed to minimize the laser power lost into
      the unwanted direction, even when the effective reflectivity of the rear fiber
      Bragg grating becomes as low as 81.5%.

PMID- 20052079
TI  - Diffracted transmission effects of GaN and polymer two-dimensional square-lattice
      photonic crystals.
AB  - The effects of the lattice pitch of GaN and polymer square-lattice photonic
      crystal (2PhC) on the diffracted transmission were studied by using rigorous
      coupled wave analysis (RCWA). Besides the first-order Bragg diffraction, higher
      order diffractions from large pitches of PhC are also significant to the light
      extraction improvement. Three different diffraction mechanisms are illustrated
      through wave vector analysis. The enhancement factors of integrated transmission
      are obtained from a wide range of pitches with micro-scale for both GaN and
      polymer 2PhC. The experimental angular-resolved transmission on a transparent
      polymer sample of 2 microm pitch 2PhC is comparable to the simulation.

PMID- 20052080
TI  - Level-set-based inverse lithography for photomask synthesis.
AB  - Inverse lithography technology (ILT) treats photomask design for microlithography
      as an inverse mathematical problem. We show how the inverse lithography problem
      can be addressed as an obstacle reconstruction problem or an extended nonlinear
      image restoration problem, and then solved by a level set time-dependent model
      with finite difference schemes. We present explicit detailed formulation of the
      problem together with the first-order temporal and second-order spatial accurate
      discretization scheme. Experimental results show the superiority of the proposed
      level set-based ILT over the mainstream gradient methods.

PMID- 20052081
TI  - Light extraction enhancement for InGaN/GaN LED by three dimensional auto-cloned
      photonics crystal.
AB  - Three dimensional (3-D) auto-cloned photonics crystal (APhC) of Ta2O5/SiO2 multi
      layers was fabricated on the backside of the sapphire wafer that had InGaN/GaN
      multi-quantum well LED on the front side. 94% light extraction enhancement in
      comparison to the LED without APhC was obtained. Electrical properties of the LED
      did not altered by the APhC and its fabrication process. Experimental evidences
      showed that light extraction enhancement mechanism is two-folded: for rays that
      are emitted from the source and incident at lower angle of incidence to the APhC,
      the APhC acts as a high reflector; for rays incident at higher angle of incidence
      to the APhC, first order diffracted light from the APhC appears, the diffracted
      light is concentrated around the surface normal and is therefore capable of
      escaping.

PMID- 20052082
TI  - Optical frequency comb generation based on repeated frequency shifting using two
      Mach-Zehnder modulators and an asymmetric Mach-Zehnder interferometer.
AB  - A novel approach to generating an optical frequency comb based on repeated
      frequency shifting is proposed and experimentally demonstrated. The frequency
      shifting is implemented via optical carrier suppression and single-sideband
      modulation using two Mach-Zehnder modulators in conjunction with a bidirectional
      asymmetric Mach-Zehnder interferometer with wavelength-shifted transmission
      spectra along the opposite directions. A theoretical analysis is performed, which
      is confirmed by a proof-of-concept experiment. A stable optical comb covering a
      spectral range of 0.18 THz is generated.

PMID- 20052083
TI  - Intra-retinal layer segmentation in optical coherence tomography images.
AB  - Retinal layer thickness, evaluated as a function of spatial position from optical
      coherence tomography (OCT) images is an important diagnostics marker for many
      retinal diseases. However, due to factors such as speckle noise, low image
      contrast, irregularly shaped morphological features such as retinal detachments,
      macular holes, and drusen, accurate segmentation of individual retinal layers is
      difficult. To address this issue, a computer method for retinal layer
      segmentation from OCT images is presented. An efficient two-step kernel-based
      optimization scheme is employed to first identify the approximate locations of
      the individual layers, which are then refined to obtain accurate segmentation
      results for the individual layers. The performance of the algorithm was tested on
      a set of retinal images acquired in-vivo from healthy and diseased rodent models
      with a high speed, high resolution OCT system. Experimental results show that the
      proposed approach provides accurate segmentation for OCT images affected by
      speckle noise, even in sub-optimal conditions of low image contrast and presence
      of irregularly shaped structural features in the OCT images.

PMID- 20052084
TI  - Utilizing critical angles in sensing partially ordered liquid crystal profile.
AB  - This paper investigates a new approach for tracking nematic uniaxial liquid
      crystal (LC) profile in partially ordered LC based sensors. This approach
      utilizes measuring critical angles for total internal reflection (TIR) at the
      interface of optically isotropic and partially ordered LC film. The proposed
      optical transduction requires measuring of the ordinary critical angle and two
      extraordinary critical angles in orthogonal directions to report the LC degree of
      ordering and the director axis orientation.

PMID- 20052085
TI  - Scanning protocols dedicated to smart velocity ranging in spectral OCT.
AB  - We introduce a new type of scanning protocols, called segmented protocols, which
      enable extracting multi-range flow velocity information from a single Spectral
      OCT data set. The protocols are evaluated using a well defined flow in a glass
      capillary. As an example of in vivo studies, we demonstrate two- and three
      dimensional imaging of the retinal vascular system in the eyes of healthy
      volunteers. The flow velocity detection is performed using a method of Joint
      Spectral and Time domain OCT. Velocity ranging is demonstrated in imaging of
      retinal vasculature in the macular region and in the optic disk area
      characterized by different flow velocity values. Additionally, an enhanced
      visualization of retinal capillary network is presented in the close proximity to
      macula.

PMID- 20052086
TI  - Spectral and electro-optic response of UV-written waveguides in LiNbO3 single
      crystals.
AB  - An experimental study of the spectral and electro-optic response of direct UV
      written waveguides in LiNbO3 is reported. The waveguides were written using c.w.
      laser radiation at 275, 300.3, 302, and 305 nm wavelengths with various writing
      powers (35-60 mW) and scan speeds (0.1-1.0 mm/sec). Spectral analysis was used to
      determine the multimode and single mode wavelength regions and, the cut-off point
      of the fabricated waveguides. Electro-optic characterization of these waveguides
      reveals that the electro-optic coefficient (r33) decreases for longer writing
      wavelengths, with a maximum of 31 pm/V for 275 nm and, is reduced to 14 pm/V for
      waveguides written with 305 nm.

PMID- 20052087
TI  - Symmetry breaking induced optical properties of gold open shell nanostructures.
AB  - We use the finite difference time domain method to predict how optical plasmon
      properties are modified if the symmetrical geometry of gold shell nanostructures
      is broken. The simulations include three kinds of gold open shell nanostructures
      of nanobowls, open nanocages, and open eggshells. For all structures, the optical
      extinction spectra commonly display a distinct red shift when the full shell
      geometry is broken and a hyperbola-like dipolar plasmonic shift when the
      fractional height continuously decreases. The optical transitions of gold open
      shell nanostructures are explained by the plasmon hybridization theory combined
      with numerical calculations. Furthermore, the calculations exhibit that the local
      electric fields are strongly enhanced at the edges of the open nanoapertures on
      those symmetry-broken structures, which suggests a potential application in
      surface-enhanced Raman spectroscopy.

PMID- 20052088
TI  - Local observation of plasmon focusingin Talbot carpets.
AB  - We present a detailed experimental and theoretical study of plasmon Talbot
      effect. A theoretical model based on simple scattering theory is developed to
      describe the Talbot self-imaging pattern generated by a linear arrangement of
      cylindrical nanostructures forming a periodic array. We first show the
      experimental observation of plasmon Talbot carpets created by propagating surface
      plasmon polaritons (SPP) interacting with cylindrical nanostructures positioned
      on a thin Au film using leakage radiation microscopy. Such images provide
      information on the distribution of the plasmon intensity close to the
      nanostructures. Next, heterodyne interferometer based near-field imaging is
      carried out to extract information on the plasmonic modes forming the Talbot
      carpet deployment. We report the experimental observation of Talbot focal spots
      with dimensions down to lambda/4.

PMID- 20052089
TI  - Differential near-field scanning optical microscopy with THz quantum cascade
      laser sources.
AB  - We have realized a differential Near-field Scanning Optical Microscope (NSOM)
      working with subwavelength resolution in the THz spectral region. The system
      employs a quantum cascade laser emitting at lambda approximately 105 microm as
      source, and the method, differently from conventional NSOM, involves diffracting
      apertures with size comparable to the wavelength. This concept ensures a higher
      signal-to-noise level at the expense of an additional computational step. In the
      implementation here reported lambda/10 resolution has been achieved; present
      limiting factors are investigated through finite difference time domain
      simulations.

PMID- 20052090
TI  - Design of a digital, ultra-broadband electro-optic switch for reconfigurable
      optical networks-on-chip.
AB  - We present a novel design for a noise-tolerant, ultra-broadband electro-optic
      switch, based on a Mach-Zehnder lattice (MZL) interferometer. We analyze the
      switch performance through rigorous optical simulations, for devices implemented
      in silicon-on-insulator with carrier-injection-based phase shifters. We show that
      such a MZL switch can be designed to have a step-like switching response,
      resulting in improved tolerance to drive-voltage noise and temperature variations
      as compared to a single-stage Mach-Zehnder switch. Furthermore, we show that
      degradation in switching crosstalk and insertion loss due to free-carrier
      absorption can be largely overcome by a MZL switch design. Finally, MZL switches
      can be designed for having an ultra-wide, temperature-insensitive optical
      bandwidth of more than 250 nm. The proposed device shows good potential as a
      broadband optical switch in reconfigurable optical networks-on-chip.

PMID- 20052091
TI  - Large area high efficiency broad bandwidth 800 nm dielectric gratings for high
      energy laser pulse compression.
AB  - We have demonstrated broad bandwidth large area (229 mm x 114 mm) multilayer
      dielectric diffraction gratings for the efficient compression of high energy 800
      nm laser pulses at high average power. The gratings are etched in the top layers
      of an aperiodic (Nb0.5Ta0.5)2O5-SiO2 multilayer coating deposited by ion beam
      sputtering. The mean efficiency of the grating across the area is better than 97%
      at the center wavelength and remains above 96% at wavelengths between 820 nm and
      780 nm. The gratings were used to compress 5.5 J pulses from a Ti:sapphire laser
      with an efficiency above 80 percent.

PMID- 20052092
TI  - Highly sensitive digital optical sensor based on cascaded high-Q ring-resonators.
AB  - A digital optical sensor based on two cascaded rings with different free spectral
      ranges (FSRs) is proposed. Because of their different FSRs, the major peak of the
      spectral response from the output port shifts digitally when the effective
      refractive index of ring #1 changes. And the shift of the major peak is equal to
      multiple FSRs of ring #2. Since it is easy to design a ring with a FSR of
      nanometers, the present digital optical sensor shows an ultra-high sensitivity
      (at the order of 10(5) nm/RIU) which is over two orders higher than that of a
      regular single-ring sensor. By using the present digital optical sensor, it
      becomes convenient to use an integrated optical micro-spectrometer (even with a
      low resolution) to monitor the peak shift of the spectral response. Therefore, it
      is promising to realize a low-cost and portable highly-sensitive optical sensor
      system on a single chip.

PMID- 20052093
TI  - Hyperspectral agricultural mapping using support vector machine-based endmember
      extraction (SVM-BEE).
AB  - Extracting endmembers from remotely-sensed images of vegetated areas can present
      difficulties. In this research, we applied a recently-developed endmember
      extraction algorithm based on Support Vector Machines to the problem of semi
      autonomous estimation of vegetation endmembers from a hyperspectral image. This
      algorithm, referred to as Support Vector Machine-Based Endmember Extraction (SVM
      BEE), accurately and rapidly yields a computed representation of hyperspectral
      data that can accommodate multiple distributions. The number of distributions is
      identified without prior knowledge, based upon this representation. Prior work
      established that SVM-BEE is robustly noise-tolerant and can semi-automatically
      estimate endmembers; synthetic data and a geologic scene were previously
      analyzed. Here we compared the efficacies of SVM-BEE, N-FINDR, and SMACC
      algorithms in extracting endmembers from a real, predominantly-agricultural
      scene. SVM-BEE estimated vegetation and other endmembers for all classes in the
      image, which N-FINDR and SMACC failed to do. SVM-BEE was consistent in the
      endmembers that it estimated across replicate trials. Spectral angle mapper (SAM)
      classifications based on SVM-BEE-estimated endmembers were significantly more
      accurate compared with those based on N-FINDR- and (in general) SMACC-endmembers.
      Linear spectral unmixing accrued overall accuracies similar to those of SAM.

PMID- 20052094
TI  - Spectrum control by anisotropy in a cylindrical microcavity.
AB  - Spectrum control by anisotropy in a cylindrical microcavity made of electric
      anisotropic medium was studied. A finite-difference time domain method for
      electric anisotropic medium and Volume-average Effective Permittivity
      approximation are applied to calculate the resonant frequencies and quality
      factors of Whispering-gallery modes. The resonant frequency for different
      whispering-gallery modes has a similar shift in direct proportion to the relative
      difference of two principal refractive indices. The quality factors decay
      exponentially due to directional emission when the difference of two principal
      refractive indices increases. This novel tuning characteristic of anisotropic
      cylindrical microcavity will play an important role in many areas, such as light
      source with tunable wavelength, tunable filter and sensor.

PMID- 20052095
TI  - Sources of possible artefacts in the contrast evaluation for the backscattering
      polarimetric images of different targets in turbid medium.
AB  - It is known that polarization-sensitive backscattering images of different
      objects in turbid media may show better contrasts than usual intensity images.
      Polarimetric image contrast depends on both target and background polarization
      properties and typically involves averaging over groups of pixels, corresponding
      to given areas of the image. By means of numerical modelling we show that the
      experimental arrangement, namely, the shape of turbid medium container, the
      optical properties of the container walls, the relative positioning of the
      absorbing, scattering and reflecting targets with respect to each other and to
      the container walls, as well as the choice of the image areas for the contrast
      calculations, can strongly affect the final results for both linearly and
      circularly polarized light.

PMID- 20052096
TI  - Effects of the surrounding medium on the optical properties of a subwavelength
      aperture.
AB  - Influence of the refractive index of the surrounding material on the performance
      of a C-shaped subwavelength aperture is investigated. The changes in the spectral
      response (0.6 microm to 6 microm wavelength range) and power throughput of the
      aperture in an optically opaque silver (Ag) film are described for two
      configurations: one where the film with the aperture is immersed in an infinite
      dielectric slab and the other where the metallic layer is immediately adjacent to
      a semi-infinite dielectric substrate. It is shown that, while the resonant
      wavelengths increase monotonically with refractive index for both cases, the
      rates of these increases, as well as the behavior of the power throughput, depend
      not only on the configuration, but also strongly on the transmission mode. These
      findings have important implications for the design of subwavelength aperture
      enhanced devices.

PMID- 20052097
TI  - Retro-detective control structures for free-space optical communication links.
AB  - A corner-cube-based retro-detection photocell is introduced. The structure
      consists of three independent and mutually perpendicular photodiodes (PDs), whose
      differential photocurrents can be used to probe the alignment state of incident
      beams. These differential photocurrents are used in an actively-controlled
      triangulation procedure to optimize the communication channel alignment in a free
      space optical (FSO) system. The active downlink and passive uplink communication
      capabilities of this system are demonstrated.

PMID- 20052098
TI  - Measured optical constants of copper from 10 nm to 35 nm.
AB  - We use laser high-order harmonics and a polarization-ratio-reflectance technique
      to determine the optical constants of copper and oxidized copper in the
      wavelength range 10-35 nm. This measurement resolves previously conflicting data
      sets, where disagreement on optical constants of copper in the extreme
      ultraviolet most likely arises from inadvertent oxidation of samples before
      measurement.

PMID- 20052099
TI  - Retrospective correction of nonuniform illumination on bi-level images.
AB  - We propose a novel method for correcting the effect of nonuniform illumination on
      a bi-level image. The proposed method is based on a penalized nonlinear least
      squares objective function that measures the binariness of an image and the
      roughness of illumination. Compared with conventional methods, it has the
      advantages of 1) not suffering from a trivial minimizer, 2) not requiring tuning
      of design parameters, and 3) effective optimization. In addition, it yields a
      unique solution since the minimization of the objective function is well-posed.
      In simulations and experiments, the method showed better accuracy and speed than
      the conventional entropy-based method.

PMID- 20052100
TI  - Optimization of few-cycle pulse generation: spatial size, mode quality and focal
      volume effects in filamentation based pulse compression.
AB  - We demonstrate the key role played by the spatial characteristics and focusing
      conditions of a femtosecond multi-cycle laser pulse in optimization of filament
      output for the purpose of obtaining compressed light pulses in the few-cycle
      regime. We find that for a given beam profile and focal parameters, driving the
      filament with energy above a certain limiting value can negatively impact pulse
      compression. However, for a given energy, a smaller and cleaner input beam mode
      obtained by using a hard aperture can substantially improve the pulse compression
      ability. In addition, we show that a larger focal volume can assist in creation
      of a shorter output pulse.

PMID- 20052101
TI  - Characterization of acceptance angles of small circular apertures.
AB  - We characterize the acceptance angles of small circular apertures for light
      collection by simulations and experimental measurements. By examining the full
      width half maximum acceptance angle as a function of the aperture size, we show
      that the acceptance angle of a circular aperture reaches a minimum of 67 deg
      before rebounding around the transition between single mode and multimode
      transmission (approximately 400 nm). This behavior can be explained by the change
      of mode-coupling efficiency during the transition from single mode to multimode
      propagation regime. This work in understanding of the behavior of light
      transmission through subwavelength apertures will guide the design of better
      aperture based imaging devices where apertures are used as light collection
      units.

PMID- 20052102
TI  - All-metal self-supported THz metamaterial--the meta-foil.
AB  - Modern metamaterials face functional constraints as they are commonly embedded in
      or deposited on dielectric materials. We provide a new solution by
      microfabricating a completely free-standing all-metal self-supported
      metamaterial. Using upright S-string architecture with the distinctive feature of
      metallic transverse interconnects, we form a locally stiff, globally flexible
      space-grid. Infrared Fourier transform interferometry reveals the typical double
      peak structure of a magnetically excited left-handed and an electrically excited
      right-handed pass-band that is maintained under strong bending and heating, and
      is sensitive to dielectrics. Exploiting UV/X-ray lithography and ultimately
      plastic moulding, meta-foils can be mass manufactured cost-effectively to serve
      as optical elements.

PMID- 20052103
TI  - Super-resolution and reconstruction of sparse sub-wavelength images.
AB  - We show that, in contrast to popular belief, sub-wavelength information can be
      recovered from the far-field of an optical image, thereby overcoming the loss of
      information embedded in decaying evanescent waves. The only requirement is that
      the image is known to be sparse, a specific but very general and wide-spread
      property of signals which occur almost everywhere in nature. The reconstruction
      method relies on newly-developed compressed sensing techniques, which we adapt to
      optical super-resolution and sub-wavelength imaging. Our approach exhibits
      robustness to noise and imperfections. We provide an experimental proof-of
      principle by demonstrating image recovery at a spatial resolution 5-times higher
      than the finest resolution defined by a spatial filter. The technique is general,
      and can be extended beyond optical microscopy, for example, to atomic force
      microscopes, scanning-tunneling microscopes, and other imaging systems.

PMID- 20052104
TI  - A simple and quantitative alignment procedure between solid state cameras.
AB  - There are many applications that use multiple charge-coupled device (CCD)
      cameras. Accordingly it is important to ensure alignment between the CCDs.
      However, a simple and quantitative alignment procedure has not been introduced
      thus far. For this reason, this paper proposes an alignment procedure that uses a
      matched filter algorithm. By using the proposed procedure, the six alignment
      errors which are x, y, z, roll, pitch, and yaw between the two CCDs can be
      eliminated. Moreover, the procedure can be applied to the alignment of more than
      two CCDs. It is believed that the proposed alignment procedure is helpful for
      precise experiments in many applications that use multiple CCDs.

PMID- 20052105
TI  - Optical performance monitoring technique using asynchronous amplitude and phase
      histograms.
AB  - We report a new optical performance monitoring technique based on the amplitude
      and phase histograms of the optical signal. The amplitude and phase histograms
      are obtained by using an intradyne receiver and the asynchronous delay-tap
      sampling method. From these histograms, we can evaluate the amplitude and phase Q
      factors of the optical signal regardless of its modulation format. In addition,
      by using these Q-factors, we can estimate the bit-error rate (BER) of the
      monitoring signal.

PMID- 20052106
TI  - Enhanced nonlinear optical properties of graphene-oligothiophene hybrid material.
AB  - The nonlinear optical and optical limiting properties of an oligothiophene
      (6THIOP) covalently functionalized graphene hybrid material (Graphene-6THIOP)
      were investigated by using Z-scan technique with a 5 ns Q-switched pulsed laser
      at 532 nm. Results show that the hybrid material of Graphene-6THIOP exhibits
      enhanced nonlinear optical and optical limiting properties in comparison to
      individual 6THIOP, graphene moiety and C60. The enhanced nonlinear optical
      properties of Graphene-6THIOP should be attributed to the combination of the
      observed nonlinear scattering with the possible photoinduced electron or energy
      transfer mechanism between 6THIOP moiety and graphene.

PMID- 20052107
TI  - Phase modulation with micromachined resonant mirrors for low-coherence fiber-tip
      pressure sensors.
AB  - This letter presents a simple phase modulation scheme for interrogation of low
      coherence interferometry based fiber-tip pressure sensors to enable real-time
      monitoring and miniaturization of the entire sensor system. The key idea is to
      introduce a sinusoidal modulation signal and retrieve the sensing cavity length
      change using a simple algorithm, without resorting to any time information. In
      experiments, phase modulation has been achieved by using a silicon-micromachined
      tunable Fabry-Perot interferometer, which is integrated with a light source and a
      photodiode onto a single chip. Compared with the conventional interrogation
      methods, this scheme possesses the merits of being less susceptible to
      disturbance, easy control and easy miniaturization, making it particularly
      suitable for sensing in constrained spaces and harsh environments.

PMID- 20052108
TI  - Novel perspectives for the application of total internal reflection microscopy.
AB  - Total Internal Reflection Microscopy (TIRM) is a sensitive non-invasive technique
      to measure the interaction potentials between a colloidal particle and a wall
      with femtonewton resolution. The equilibrium distribution of the particle-wall
      separation distance z is sampled monitoring the intensity I scattered by the
      Brownian particle under evanescent illumination. Central to the data analysis is
      the knowledge of the relation between I and the corresponding z, which typically
      must be known a priori. This poses considerable constraints to the experimental
      conditions where TIRM can be applied (short penetration depth of the evanescent
      wave, transparent surfaces). Here, we introduce a method to experimentally
      determine I(z) by relying only on the distance-dependent particle-wall
      hydrodynamic interactions. We demonstrate that this method largely extends the
      range of conditions accessible with TIRM, and even allows measurements on highly
      reflecting gold surfaces where multiple reflections lead to a complex (z).

PMID- 20052109
TI  - Efficient generation of near infra-red single photons from the zero-phonon line
      of a single molecule.
AB  - Using the zero-phonon line (ZPL) emission of a single molecule, we realized a
      triggered source of near-infra-red (lambda = 785 nm) single photons at a high
      repetition rate. A Weierstrass solid immersion lens is used to image single
      molecules with an optical resolution of 300 nm (approximately 0.4lambda) and a
      high collection efficiency. Because dephasing of the transition dipole due to
      phonons vanishes at liquid helium temperatures, our source is attractive for the
      efficient generation of single indistinguishable photons.

PMID- 20052110
TI  - Light trapping cavity enhanced light transmission through a single sub-wavelength
      aperture in a metal film.
AB  - We demonstrate that optical transmission of a normally incident, monochromatic
      plane wave through a single sub-wavelength aperture in an opaque metal film can
      be substantially enhanced by a thin, semitransparent metal film placed parallel
      to the opaque metal film in front of the aperture. When the semi-transparent and
      the opaque metal film are separated by a proper distance, a light trapping cavity
      is formed and the sub-wavelength aperture exhibits a transmission maximum. An
      enhancement factor of approximately 40 is demonstrated for a cylindrical 100 nm
      diameter hole in a silver film.

PMID- 20052111
TI  - Size effect of high contrast gratings in VCSELs.
AB  - We report on the effects of shrinking the physical size of a high index contrast
      grating (HCG) on a vertical cavity surface-emitting laser (VCSEL). HCGs
      previously had been simulated assuming infinite periodicity. Here we probe
      through simulation and experiment the effect of reducing the HCG to only a few
      periods. We experimentally realize lasing VCSELs with as few as 4 periods of HCG.
      By shrinking the HCG to an extremely small size and integrating it on a
      wavelength tunable VCSEL, we are able to achieve a tunable VCSEL with a record
      fast mechanical tuning response of >27 MHz. This is a 5X improvement over the
      fastest previously reported wavelength tunable VCSELs.

PMID- 20052112
TI  - 100 W all fiber picosecond MOPA laser.
AB  - A high power picosecond laser is constructed in an all fiber master oscillator
      power amplifier (MOPA) configuration. The seed source is an ytterbium-doped
      single mode fiber laser passively mode-locked by a semiconductor saturable
      absorber mirror (SESAM). It produces 20 mW average power with 13 ps pulse width
      and 59.8 MHz repetition rate. A direct amplification of this seed source
      encounters obvious nonlinear effects hence serious spectral broadening at only
      ten watt power level. To avoid these nonlinear effects, we octupled the
      repetition rate to about 478 MHz though a self-made all fiber device before
      amplification. The ultimate output laser exhibits an average power of 96 W, a
      pulse width of 16 ps, a beam quality M2 of less than 1.5, and an optical
      conversion efficiency of 61.5%.

PMID- 20052113
TI  - A theoretical description of Fourier domain mode locked lasers.
AB  - The first theoretical model of Fourier domain mode locking operation is
      presented. A specially tailored dynamic equation in a moving spectral reference
      frame is derived, enabling efficient numerical treatment, despite the broad laser
      spectrum and the extremely long cavity. The excellent agreement of the presented
      theory with experiment over a wide range of operation parameters enables a
      quantitative assessment of the relevant physical effects, such as the spectral
      loss modulation and gain saturation dynamics, amplified spontaneous emission,
      linewidth enhancement, and self-phase modulation.

PMID- 20052114
TI  - Low-power, 2 x 2 silicon electro-optic switch with 110-nm bandwidth for broadband
      reconfigurable optical networks.
AB  - We present an ultra-broadband Mach-Zehnder based optical switch in silicon,
      electrically driven through carrier injection. Crosstalk levels lower than -17 dB
      are obtained for both the 'on' and 'off' switching states over an optical
      bandwidth of 110 nm, owing to the implementation of broadband 50% couplers. Full
      2 x 2 switching functionality is demonstrated, with low power consumption
      (approximately 3 mW) and a fast switching time (< 4 ns). The utilization of
      standard CMOS metallization results in a low drive voltage (approximately 1 V)
      and a record-low V(pi)L (approximately 0.06 V x mm). The wide optical bandwidth
      is maintained for temperature variations up to 30 K.

PMID- 20052115
TI  - Remote surface enhanced Raman spectroscopy imaging via a nanostructured optical
      fiber bundle.
AB  - Remote surface enhanced Raman spectroscopy (SERS) imaging of an adsorbed
      monolayer was demonstrated through a nanostructured array of conical tips
      inscribed onto the distal face of a 30 cm optical fiber bundle. Despite intense
      Raman signal from the germanium oxide doped fibers, the Raman signal of an
      adsorbed monolayer of a reference compound (benzene thiol) was detected in the
      fingerprint region. This opens up the possibility of local remote imaging through
      an optical fiber that embeds a SERS active platform.

PMID- 20052116
TI  - An application of the SMS method for imaging designs.
AB  - The Simultaneous Multiple Surface (SMS) method in planar geometry (2D) is applied
      to imaging designs, generating lenses that compare well with aplanatic designs.
      When the merit function utilizes image quality over the entire field (not just
      paraxial), the SMS strategy is superior. In fact, the traditional aplanatic
      approach is actually a particular case of the SMS strategy.

PMID- 20052117
TI  - Theoretical analysis of spectrally encoded endoscopy.
AB  - Using a single optical fiber and miniature distal optics, spectrally-encoded
      endoscopy (SEE) has been demonstrated as a promising, three-dimensional
      endoscopic imaging method with a large number of resolvable points and high frame
      rates. We present a detailed theoretical study of the SEE prototype system and
      probe. Several key imaging parameters of SEE are thoroughly derived and
      formulated, including the three-dimensional point-spread function and field of
      view, as well as the system's optical aberrations and fundamental limits. We find
      that the point-spread function of the SEE system maintains a unique relation
      between its transverse and axial shapes, discuss the asymmetry of the volumetric
      field of view, determine that the number of lateral resolvable points is nearly
      twice than what was previously accepted, and derive an expression for the upper
      limit for the total number of resolvable points in the cross-sectional image
      plane.

PMID- 20052118
TI  - Frequency-domain simulations of a negative-index material with embedded gain.
AB  - We solve the equations governing light propagation in a negative-index material
      with embedded nonlinearly saturable gain material using a frequency-domain model.
      We show that available gain materials can lead to complete loss compensation only
      if they are located in the regions where the field enhancement is maximal. We
      study the increased enhancement of the fields in the gain composite as well as in
      the metal inclusions and show analytically that the effective gain is determined
      by the average near-field enhancement.

PMID- 20052119
TI  - Spatially dispersive regenerative amplification of ultrashort laser pulses.
AB  - A novel CPA-system with a spatially dispersive Yb:KYW-based regenerative
      amplifier is presented. Three prisms inside the amplifier divide the seed pulses
      from an Yb fiber laser system into spatially separated spectral components that
      pass through different volumes of the active medium and are amplified
      independently. This concept allows overcoming the effect of gain-narrowing. The
      spatially dispersive amplifier delivers laser pulses with energies of up to 30
      microJ at a repetition rate of 100 kHz. Successful compression of the amplified
      pulses down to 171 fs is demonstrated.

PMID- 20052120
TI  - General properties of dielectric optical antennas.
AB  - Using Mie theory we derive a number of general results concerning the resonances
      of spherical and cylindrical dielectric antennas. Specifically, we prove that the
      peak scattering cross-section of radiation-limited antennas depends only on the
      resonance frequency and thus is independent of refractive index and size, a
      result which is valid even when the resonator is atomic-scale. Furthermore, we
      derive scaling limits for the bandwidth of dielectric antennas and describe a
      cylindrical mode which is unique in its ability to support extremely large
      bandwidths even when the particle size is deeply subwavelength. Finally, we show
      that higher Q antennas may couple more efficiently to an external load, but the
      optimal absorption cross-section depends only on the resonance frequency.

PMID- 20052121
TI  - The transmission characteristics of surface plasmon polaritons in ring resonator.
AB  - A two-dimensional nanoscale structure which consists of two metal-insulator-metal
      (MIM) waveguides coupled to each other by a ring resonator is designed. The
      transmission characteristics of surface plasmon polaritons are studied in this
      structure. There are several types of modes in the transmission spectrum. These
      modes exhibit red shift when the radius of the ring increases. The transmission
      properties of such structure are simulated by the Finite-Difference Time-Domain
      (FDTD) method, and the eignwavelengths of the ring resonator are calculated
      theoretically. Results obtained by the theory of the ring resonator are
      consistent with those from the FDTD simulations.

PMID- 20052122
TI  - Dynamic micro-bead arrays using optical tweezers combined with intelligent
      control techniques.
AB  - Dynamic micro-bead arrays offer great flexibility and potential as sensing tools
      in various scientific fields. Here we present a software-oriented approach for
      fully automated assembly of versatile dynamic micro-bead arrays using multi-beam
      optical tweezers combined with intelligent control techniques. Four typical
      examples, including the collision-free sorting of array elements by bead
      features, are demonstrated in real time. Control algorithms and experimental
      apparatus for these demonstrations are also described.

PMID- 20052123
TI  - Solving dielectric and plasmonic waveguide dispersion relations on a pocket
      calculator.
AB  - We present a robust iterative technique for solving complex transcendental
      dispersion equations routinely encountered in integrated optics. Our method
      especially befits the multilayer dielectric and plasmonic waveguides forming the
      basis structures for a host of contemporary nanophotonic devices. The solution
      algorithm ports seamlessly from the real to the complex domain--i.e., no extra
      complexity results when dealing with leaky structures or those with
      material/metal loss. Unlike several existing numerical approaches, our algorithm
      exhibits markedly-reduced sensitivity to the initial guess and allows for
      straightforward implementation on a pocket calculator.

PMID- 20052124
TI  - Compact fiber amplifier pumped OPCPA system delivering Gigawatt peak power 35 fs
      pulses.
AB  - We report on a compact Gigawatt peak power OPCPA system which is pumped by the
      second harmonic of an Yb-doped fiber amplifier and seeded by a cavity dumped
      Ti:Sapphire oscillator. Picosecond pump pulses for the OPCPA are generated by
      spectral filtering and directly amplified to 1 mJ pulse energy in several fiber
      amplifiers, without the need of chirped pulse amplification. Since no stretcher
      and compressor is required, the pump laser is very compact and easy to operate.
      The two stage optical parametric amplifier delivers 35 fs pulses with 53 microJ
      pulse energy and 1.1 GW peak power at 40 kHz repetition rate. Additionally, the
      scaling potential of this approach is discussed.

PMID- 20052125
TI  - Calculation of femtosecond pulse laser induced damage threshold for broadband
      antireflective microstructure arrays.
AB  - In order to more exactly predict femtosecond pulse laser induced damage
      threshold, an accurate theoretical model taking into account photoionization,
      avalanche ionization and decay of electrons is proposed by comparing respectively
      several combined ionization models with the published experimental measurements.
      In addition, the transmittance property and the near-field distribution of the
      'moth eye' broadband antireflective microstructure directly patterned into the
      substrate material as a function of the surface structure period and groove depth
      are performed by a rigorous Fourier model method. It is found that the near-field
      distribution is strongly dependent on the periodicity of surface structure for TE
      polarization, but for TM wave it is insensitive to the period. What's more, the
      femtosecond pulse laser damage threshold of the surface microstructure on the
      pulse duration taking into account the local maximum electric field enhancement
      was calculated using the proposed relatively accurate theoretical ionization
      model. For the longer incident wavelength of 1064 nm, the weak linear damage
      threshold on the pulse duration is shown, but there is a surprising oscillation
      peak of breakdown threshold as a function of the pulse duration for the shorter
      incident wavelength of 532 nm.

PMID- 20052126
TI  - Characterization of nanostructured VO2 thin films grown by magnetron controlled
      sputtering deposition and post annealing method.
AB  - By magnetron controlled sputtering system, a new nanostructured metastable
      monoclinic phase VO2 (B) thin film has been fabricated. The testing result shows
      that this nanostructured VO2 (B) thin film has high temperature coefficient of
      resistance (TCR) of -7%/K. Scanning electron microscopy measurement shows that
      the average grain diameter of the VO2 (B) crystallite is between 100 and 250 nm.
      After post annealed, VO2 (B) crystallite is changed into monoclinic (M) phase VO2
      (M) crystallite with the average grain diameter between 20 and 50 nm. A set up of
      testing the thin film switching time is established. The test result shows the
      switching time is about 50 ms. With the nanostructured VO2 (B) and VO2 (M) thin
      films, optical switches and high sensitivity detectors will be presented.

PMID- 20052127
TI  - Spectroscopic measurements with dispersion encoded full range frequency domain
      optical coherence tomography in single- and multilayered non-scattering phantoms.
AB  - In this study, depth resolved measurements of absorption profiles in the
      wavelength range of 800 nm with a bandwidth of 140 nm are demonstrated using high
      speed spectroscopic frequency domain OCT(SOCT) and a full range reconstruction
      algorithm (dispersion encoded full range, DEFR). The feasibility of the algorithm
      for SOCT is tested in simulation and experiment. With proper calibration, SOCT
      with DEFR is able to extract absolute, depth resolved absorption profiles over
      the whole wavelength range at once without the need of tuning and performing
      measurements at single wavelengths sequentially. The superior acquisition speed
      and better phase stability in frequency domain as compared to time domain results
      in a better reproducibility and practicability for spectroscopic measurements. In
      addition, high acquisition speed in excess of 20 kHz allows to measure absorption
      dynamics with 50 micros time resolution, which might be useful for the
      investigation of pharmacokinetics or pharmacodynamics. SOCT of approximately 600
      microm thick single- and multilayered, weakly scattering phantoms with varying
      absorption in the range of 5-80 cm(-1), equivalent to blood absorption in
      capillaries, is presented. SOCT measurements are compared with those using a
      spectrometer in transmission mode. For Indocyanine Green (ICG), a dynamic
      absorption measurements are demonstrated.

PMID- 20052128
TI  - Thick optical waveguides in lithium niobate induced by swift heavy ions
      (approximately 10 MeV/amu) at ultralow fluences.
AB  - Heavy mass ions, Kr and Xe, having energies in the approximately 10 MeV/amu range
      have been used to produce thick planar optical waveguides at the surface of
      lithium niobate (LiNbO3). The waveguides have a thickness of 40-50 micrometers,
      depending on ion energy and fluence, smooth profiles and refractive index jumps
      up to 0.04 (lambda = 633 nm). They propagate ordinary and extraordinary modes
      with low losses keeping a high nonlinear optical response (SHG) that makes them
      useful for many applications. Complementary RBS/C data provide consistent values
      for the partial amorphization and refractive index change at the surface. The
      proposed method is based on ion-induced damage caused by electronic excitation
      and essentially differs from the usual implantation technique using light ions (H
      and He) of MeV energies. It implies the generation of a buried low-index layer
      (acting as optical barrier), made up of amorphous nanotracks embedded into the
      crystalline lithium niobate crystal. An effective dielectric medium approach is
      developed to describe the index profiles of the waveguides. This first test
      demonstration could be extended to other crystalline materials and could be of
      great usefulness for mid-infrared applications.

PMID- 20052129
TI  - A new method for fabricating high density and large aperture ratio liquid
      microlens array.
AB  - Conventional liquid microlens arrays are facing bottlenecks in controlling
      droplet size and shape, and limited aperture ratio. We report a new
      liquid/solvent approach to overcome these obstacles for making uniform droplet
      array and achieving approximately 90% aperture ratio. The droplets are very
      stable due to the pinning effect of the polymer walls and substrate surfaces.
      Using the fabricated droplet array, we demonstrate a tunable-focus microlens
      array based on dielectrophoretic effect. The microlens array exhibits a large
      dynamic range and fast response time (tens of milliseconds). Besides liquid
      microlens arrays, this fabrication method also opens a new door for making other
      tunable photonic devices.

PMID- 20052130
TI  - An anisotropic negative refractive index medium operated at multiple-angle
      incidences.
AB  - Recently metamaterials have been demonstrating new physics to enable various
      unprecedented electromagnetic properties, but pratically they are so sensitive to
      incident angles of the external excitation that their applications are
      restricted. Therefore, we present an anisotropic negative refractive index medium
      operated at multiple-angle incidences (NRIM for MAI) to ease such a burden. Both
      the simulated and measured transmittance, reflectance and the corresponding
      material parameters indicate that our structure does possess the anisotropic
      negative refractive index with respect to different incident angles. In addition,
      the opposite directions of group and phase velocities are also demonstrated under
      both grazing-angle, normal and 45-degree incidences to further verify the
      negative refractive index of the designed monolithic NRIM structure for multiple
      angle incidences.

PMID- 20052131
TI  - Global evaluation of closed-loop electron dynamics in quasi-one-dimensional
      conductors using polarization vortices.
AB  - We evaluate the quasi-one-dimensional (1D) electron dynamics in a NbSe3 ring
      crystal using polarization vortex pulses with various azimuthal distributions.
      The single particle relaxation component reveals a large anisotropy on the
      crystal, indicating that the electrons in the ring maintain their 1D character.
      The results also suggest that the polarization vortex evaluates the global
      polarization property of the closed-loop electron that plays an important role in
      the quantum correlation phenomena such as the Aharonov-Bohm effect.

PMID- 20052132
TI  - Image reconstruction in diffuse optical tomography based on simplified spherical
      harmonics approximation.
AB  - The use of higher order approximations to the Radiative transport equation,
      through simplified spherical harmonics expansion (SP(N)) in optical tomography
      are presented. It is shown that, although the anisotropy factor can be modeled in
      the forward problem, its sensitivity to the measured boundary data is limited to
      superficial regions and more importantly, due to uniqueness of the inverse
      problem it cannot be determined using frequency domain data. Image reconstruction
      through the use of higher ordered models is presented. It is demonstrated that at
      higher orders (for example SP7) the image reconstruction becomes highly under
      determined due to the large increase in the number of unknowns which cannot be
      adequately recovered. However, reconstruction of diffuse parameters, namely
      optical absorption and reduced scatter have shown to be more accurate where only
      the sensitivity matrix used in the inverse problem is based on SP(N) method and
      image reconstruction is limited to these two diffuse parameters.

PMID- 20052133
TI  - Sub-wavelength nanofluidics in photonic crystal sensors.
AB  - We introduce a novel sensor scheme combining nano-photonics and nano-fluidics on
      a single platform through the use of free-standing photonic crystals. By
      harnessing nano-scale openings, we theoretically and experimentally demonstrate
      that both fluidics and light can be manipulated at sub-wavelength scales.
      Compared to the conventional fluidic channels, we actively steer the convective
      flow through the nanohole openings for effective delivery of the analytes to the
      sensor surface. We apply our method to detect refractive index changes in aqueous
      solutions. Bulk measurements indicate that active delivery of the convective flow
      results in better sensitivities. The sensitivity of the sensor reaches 510 nm/RIU
      for resonance located around 850 nm with a line-width of approximately 10 nm in
      solution. Experimental results are matched very well with numerical simulations.
      We also show that cross-polarization measurements can be employed to further
      improve the detection limit by increasing the signal-to-noise ratio.

PMID- 20052134
TI  - Soft-landing and optical characterization of a preselected single fluorescent
      particle on a tapered optical fiber.
AB  - Tapered optical fibers offer easy access to the evanescent field of their guided
      modes which is ideal for sensing applications. We introduce a soft-landing
      technique utilizing a linear Paul trap to select and place a single microparticle
      on the surface of a tapered optical fiber. This approach allows on-demand
      functionalization of fragile nanophotonic components with arbitrary particles,
      e.g., for advanced nanosensors.

PMID- 20052135
TI  - A 24 km fiber-based discretely signaled continuous variable quantum key
      distribution system.
AB  - We report a continuous variable key distribution system that achieves a final
      secure key rate of 3.45 kilobits/s over a distance of 24.2 km of optical fiber.
      The protocol uses discrete signaling and post-selection to improve reconciliation
      speed and quantifies security by means of quantum state tomography. Polarization
      multiplexing and a frequency translation scheme permit transmission of a
      continuous wave local oscillator and suppression of noise from guided acoustic
      wave Brillouin scattering by more than 27 dB.

PMID- 20052136
TI  - Compact and passive-alignment 4-channel x 2.5-Gbps optical interconnect modules
      based on silicon optical benches with 45 degrees micro-reflectors.
AB  - Compact and passive-alignment 4-channel x 2.5-Gbps optical interconnect modules
      are developed based on the silicon optical benches (SiOBs) of 5 x 5 mm2. A
      silicon-based 45 degrees micro-reflector and V-groove arrays are fabricated on
      the SiOB using anisotropic wet etching. Moreover, high-frequency transmission
      lines of 4 channel x 2.5 Gbps, and bonding pads with Au/Sn eutectic solder are
      also deposited on the SiOB. The vertical-cavity surface-emitting laser (VCSEL)
      array and photo-detector (PD) array are flip-chip assembled on the intended
      positions. The multi-mode fiber (MMF) ribbons are passively aligned and mounted
      onto the V-groove arrays. Without the assistance of additional optics, the
      coupling efficiencies of VCSEL-to-MMF in the transmitting part and MMF-to-PD in
      the receiving part can be as high as -5.65 and -1.98 dB, respectively, under an
      optical path of 180 microm. The 1-dB coupling tolerance of greater than +/- 20
      microm is achieved for both transmitting and receiving parts. Eye patterns of
      both parts are demonstrated using 15-bit PRBS at 2.5 Gbps.

PMID- 20052137
TI  - Lithium niobate photonic wires.
AB  - LN photonic wires of cross-section dimensions down to 1 x 0.73 microm2 were
      fabricated by Ar milling of a single-crystalline LiNbO3 (LN) film bonded to a
      SiO2/LiNbO3 substrate. Mode intensity distributions, propagation losses, and
      group indices of refraction were measured at 1.55 microm wavelength and compared
      with simulation results. Moreover, effective mode indices and end face
      reflectivities were numerically evaluated. The waveguide of 1 microm top width is
      the smallest LN photonic wire reported to date; it has a mode size of
      approximately 0.4 microm2 (0.5 microm2) only and propagation losses of 9.9 dB/cm
      (12.9 dB/cm) for qTM (qTE) polarization.

PMID- 20052138
TI  - Direct and inverse discrete Zernike transform.
AB  - An invertible discrete Zernike transform, DZT is proposed and implemented. Three
      types of non-redundant samplings, random, hybrid (perturbed deterministic) and
      deterministic (spiral) are shown to provide completeness of the resulting sampled
      Zernike polynomial expansion. When completeness is guaranteed, then we can obtain
      an orthonormal basis, and hence the inversion only requires transposition of the
      matrix formed by the basis vectors (modes). The discrete Zernike modes are given
      for different sampling patterns and number of samples. The DZT has been
      implemented showing better performance, numerical stability and robustness than
      the standard Zernike expansion in numerical simulations. Non-redundant (critical)
      sampling along with an invertible transformation can be useful in a wide variety
      of applications.

PMID- 20052139
TI  - Quantum cascade laser gain enhancement by front facet illumination.
AB  - Optical gain enhancement is demonstrated in a standard mid-infrared quantum
      cascade laser in pulse operation, using a near infrared illumination on the laser
      facet. An increase in the laser emission is observed, as well as greater dynamic
      range, threshold reduction, and a blue shift in the laser cavity modes. The
      optically induced gain increase allows for optical switching of the laser. All
      the changes have a nonlinear dependency on the illumination optical power and are
      attributed to the free carrier concentration increase and the electron transport
      change in the active region due to the near infrared illumination.

PMID- 20052140
TI  - Nanoplasmonics of prime number arrays.
AB  - In this paper, we investigate the plasmonic near-field localization and the far
      field scattering properties of non-periodic arrays of Ag nanoparticles generated
      by prime number sequences in two spatial dimensions. In particular, we
      demonstrate that the engineering of plasmonic arrays with large spectral flatness
      and particle density is necessary to achieve a high density of electromagnetic
      hot spots over a broader frequency range and a larger area compared to strongly
      coupled periodic and quasi-periodic structures. Finally, we study the far-field
      scattering properties of prime number arrays illuminated by plane waves and we
      discuss their angular scattering properties. The study of prime number arrays of
      metal nanoparticles provides a novel strategy to achieve broadband enhancement
      and localization of plasmonic fields for the engineering of nanoscale nano
      antenna arrays and active plasmonic structures.

PMID- 20052141
TI  - Limiting factors to the OCT axial resolution for in-vivo imaging of human and
      rodent retina in the 1060 nm wavelength range.
AB  - A computational model was developed to evaluate the limitations to the highest
      axial resolution, achievable with ultrahigh resolution optical coherence
      tomography (UHROCT) in the 1060 nm wavelength region for in-vivo imaging of the
      human and rodent retina. The model considers parameters such as the wavelength
      dependent water absorption, the average length of the human and rodent eyes, and
      the power limitations for the imaging beam as defined in the ANSI standard. A
      custom-built light source with re-shaped spectrum was used to verify
      experimentally the results from the computational model. Axial OCT resolution of
      4.2 microm and 7.7 microm was measured from a mirror reflection with the custom
      light source by propagating the imaging beam through water cells with 5 mm and 25
      mm thickness, corresponding to the average axial length of the rodent and human
      eye respectively. Assuming an average refractive index of 1.38 for retinal
      tissue, the expected axial OCT resolution in the rodent and human retina is 3
      microm and 5.7 microm respectively. Retinal tomograms acquired in-vivo from the
      rat eye with the modified light source show clear visualization of all
      intraretinal layers, as well as a network of capillaries (approximately 10 microm
      in diameter) in the inner- and outer plexiform layers of the retina.

PMID- 20052142
TI  - Experimental and theoretical investigations of photonic crystal fiber amplifier
      with 260 W output.
AB  - We report on a polarization-maintaining narrow-linewidth high power ytterbium
      doped photonic crystal fiber amplifier with an output as high as 260 W and a
      slope efficiency of approximately 74%. Measurements of the beam quality yielded
      M2 values in the range of 1.2-1.3. The linewidth was determined at two different
      powers using an optical heterodyne detection technique and yielded values that
      were less than 10 KHz. Our maximum output power was pump limited and measurements
      of the reflected light indicated that we operated below the stimulated Brillouin
      scattering (SBS) threshold. Using a pump-probe technique, we estimated the
      Brillouin gain bandwidth to be approximately 68 MHz. In addition, the Brillouin
      gain spectrum revealed secondary peaks lying at the high-frequency side. In order
      to study the power limitations of our amplifier, we developed a detailed model
      that included a distributed noise source for the SBS process and a temperature
      gradient obtained via quantum defect heating. Our simulations indicated that for
      this particular fiber amplifier configuration an output power approaching 1 KW
      can be achieved. We also found that for forced air cooling the SBS threshold
      saturates regardless of the operating temperature of the polymer coating.
      Finally, we show that relatively small enhancement is obtained if a continuous
      transverse acoustic velocity gradient was implemented in conjunction with the
      thermal gradient. The latter conclusions drawn from our simulations also hold
      true for conventional fibers.

PMID- 20052143
TI  - Encapsulated subwavelength grating as a quasi-monolithic resonant reflector.
AB  - For a variety of laser interferometric experiments, the thermal noise of high
      reflectivity multilayer dielectric coatings limits the measurement sensitivity.
      Recently, monolithic high-reflection waveguide mirrors with nanostructured
      surfaces have been proposed to reduce the thermal noise in interferometric
      measurements. Drawbacks of this approach are a highly complicated fabrication
      process and the high susceptibility of the nanostructured surfaces to damage and
      pollution. Here, we propose and demonstrate a novel quasi-monolithic resonant
      surface reflector that also avoids the thick dielectric stack of conventional
      mirrors but has a flat and robust surface. Our reflector is an encapsulated
      subwavelength grating that is based on silicon. We measured a high reflectivity
      of 93% for a wavelength of lambda = 1.55 microm under normal incidence. Perfect
      reflectivities are possible in theory.

PMID- 20052144
TI  - Multi-mode mitigation in an optofluidic chip for particle manipulation and
      sensing.
AB  - A new waveguide design for an optofluidic chip is presented. It mitigates multi
      mode behavior in solid and liquid-core waveguides by increasing fundamental mode
      coupling to 82% and 95%, respectively. Additionally, we demonstrate a six-fold
      improvement in lateral confinement of optically guided dielectric microparticles
      and double the detection efficiency of fluorescent particles.

PMID- 20052145
TI  - Electrical detection of plasmonic waves using an ultra-compact structure via a
      nanocavity.
AB  - A novel structure is proposed to electrically detect the plasmonic waves from a
      subwavelength plasmonic waveguide. By locating two L-shaped metallic nanorods in
      close proximity of each other at the end of the plasmonic waveguide, a metal
      semiconductor-metal plasmonic detector is constructed. The L-shaped nanorods also
      form a dipole nanoantenna and a nanocavity to focus the photonic power into the
      active volume of the detector. The dimensions and locations of the L-shaped
      nanorods are studied to maximize the transmission efficiency of the photonic
      power from the plasmonic waveguide to the detector. Impedance matching with a sub
      is investigated to further improve the power transmission. Possible leads of the
      detector are discussed and their effects are investigated. Proposed detector has
      an ultra-compact and easy-to-fabricate planar structure, and a potentially THz
      speed, high responsivity as well as low power dissipation.

PMID- 20052146
TI  - Adiabatically induced coherent Josephson oscillations of ultracold atoms in an
      asymmetric two-dimensional magnetic lattice.
AB  - We propose a new method to create an asymmetric two-dimensional magnetic lattice
      which exhibits magnetic band gap structure similar to semiconductor devices. The
      quantum device is assumed to host bound states of collective excitations formed
      in a magnetically trapped quantum degenerate gas of ultracold atoms such as a
      Bose-Einstein condensate (BEC) or a degenerate Fermi gas. A theoretical framework
      is established to describe possible realization of the exciton-Mott to
      discharging Josephson states oscillations in which the adiabatically controlled
      oscillations induce ac and dc Josephson atomic currents where this effect can be
      used to transfer n Josephson qubits across the asymmetric two-dimensional
      magnetic lattice. We consider second-quantized Hamiltonians to describe the Mott
      insulator state and the coherence of multiple tunneling between adjacent magnetic
      lattice sites where we derive the self consistent non-linear Schrodinger equation
      with a proper field operator to describe the exciton Mott quantum phase
      transition via the induced Josephson atomic current across the n magnetic bands.

PMID- 20052147
TI  - Transparency induced by coupled resonances in disordered metamaterials.
AB  - We propose a scheme to induce transparency in one-dimensional disordered
      multilayers which are composed of negative permittivity and negative permeability
      metamaterials. First, analytical expressions for transparency condition are
      derived exactly, providing us a picture that complete tunneling in such kind of
      multiple-resonance system can be achieved if exponentially growing waves can
      compensate exponentially decaying waves. Second, a compensating method is used to
      realize this idea, and both simulations and experiments are performed in the
      microwave regime to confirm the theoretical analysis. Last, we have a discussion
      on how the coupling of resonances affects the transport properties of samples.

PMID- 20052148
TI  - A comparative study of high resolution microscopy imaging modalities using a
      three-dimensional resolution measure.
AB  - From an acquired image, single molecule microscopy makes possible the
      determination of the distance separating two closely spaced biomolecules in three
      dimensional (3D) space. Such distance information can be an important indicator
      of the nature of the biomolecular interaction. Distance determination, however,
      is especially difficult when, for example, the imaged point sources are very
      close to each other or are located near the focal plane of the imaging setup. In
      the context of such challenges, we compare the limits of the distance estimation
      accuracy for several high resolution 3D imaging modalities. The comparisons are
      made using a Cramer-Rao lower bound-based 3D resolution measure which predicts
      the best possible accuracy with which a given distance can be estimated.
      Modalities which separate the detection of individual point sources (e.g., using
      photoactivatable fluorophores) are shown to provide the best accuracy limits when
      the two point sources are very close to each other and/or are oriented near
      parallel to the optical axis. Meanwhile, modalities which implement the
      simultaneous imaging of the point sources from multiple focal planes perform best
      when given a near-focus point source pair. We also demonstrate that the maximum
      likelihood estimator is capable of attaining the limit of the accuracy predicted
      for each modality.

PMID- 20052149
TI  - An optical imaging method to monitor stem cell migration in a model of immune
      mediated arthritis.
AB  - The objective of this work is to establish an optical imaging technique that
      would enable monitoring of the integration of mesenchymal stem cells (MSC) in
      arthritic joints. Our approach is based on first developing a labeling technique
      of MSC with the fluorescent dye DiD followed by tracking the cell migration
      kinetics from the spatial distribution of the DiD fluorescence in optical images
      (OI). The experimental approach involves first the in vitro OI of MSC labeled
      with DiD accompanied by fluorescence microscopy measurements to establish
      localization of the signal within the cells. Thereafter, DiD-labeled MSC were
      injected into polyarthritic, athymic rats and the signal localization within the
      experimental animals was monitored over several days. The experimental results
      indicate that DiD integrated into the cell membrane. DiD-labeled MSC localization
      in the arthritic ankle joints was observed with OI indicating that this method
      can be applied to monitor MSC in arthritic joints.

PMID- 20052150
TI  - Broadband hitless silicon electro-optic switch for on-chip optical networks.
AB  - We report on the demonstration of a broadband (60 GHz), spectrally hitless,
      compact (20 microm x 40 microm), fast (7 ns) electro-optical switch. The device
      is composed of two coupled resonant cavities, each with an independently
      addressable PIN diode. This topology enables operation of the switch without
      perturbing adjacent channels in a wavelength division multiplexing (WDM) system.

PMID- 20052151
TI  - Three-color multiplex CARS for fast imaging and microspectroscopy in the entire
      CHn stretching vibrational region.
AB  - We present a three-color multiplex coherent anti-Stokes Raman scattering (CARS)
      setup that facilitates a prompt recording of broadband CARS spectra along with a
      fast CARS imaging. With separate narrowband Stokes and probe beams being
      introduced in the near IR, we are able to incorporate a stable, wideband
      Ti:sapphire femtosecond laser as a pump beam that covers the full range of Raman
      shift for CHn stretching vibrational modes. Experimentally, high-resolution
      multiplex CARS signals are allowed to investigate molecular vibrations over the
      range of 2650 cm-1 - 3050 cm-1, which are spectrally integrated to construct
      lipid-sensitive images. It is demonstrated that the proposed implementation
      promises a particular benefit on CARS imaging of lipid-rich tissue structures by
      providing detailed information on CHn Raman-active vibrations at points of
      interest on the CARS images that can be obtained at high frame rates.

PMID- 20052152
TI  - Low-cost high-performance fiber-optic pH sensor based on thin-core fiber modal
      interferometer.
AB  - A new fiber-optic pH sensor based on a thin-core fiber modal interferometer with
      electrostatic self-assembled nanocoating is presented. After inserting a segment
      of thin-core fiber into a standard single-mode fiber, high-order cladding modes
      are excited and interfere with the core mode to form an in-fiber modal
      interferometer. The side surface of the sensor is then deposited with
      poly(allylamine hydrochloride) and poly(acrylic acid) nanocoating by
      electrostatic self-assembly technique. A fast and linear response is obtained in
      either acid or alkali solution (in the pH range 2.5 to 10) with resolution of
      0.013 pH unit.

PMID- 20052153
TI  - Continuous-wave optical parametric terahertz source.
AB  - Here, we present a continuous-wave optical parametric terahertz light source that
      does not require cooling. It coherently emits a diffraction-limited terahertz
      beam that is tunable from 1.3 to 1.7 THz with power levels exceeding 1 microW.
      Simultaneous phase matching of two nonlinear processes within one periodically
      poled lithium niobate crystal, situated in an optical resonator, is employed: The
      signal wave of a primary parametric process is enhanced in this resonator.
      Therefore, its power is sufficient for starting a second process, generating a
      backwards traveling terahertz wave. Such a scheme of cascaded processes increases
      the output power of a terahertz system by more than one order of magnitude
      compared with non-resonant difference frequency generation due to high
      intracavity powers. The existence of linearly polarized terahertz radiation at
      1.35 THz is confirmed by analyzing the terahertz light with metal grid polarizers
      and a Fabry-Perot interferometer.

PMID- 20052154
TI  - Evaluation of InGaN/GaN light-emitting diodes of circular geometry.
AB  - Blue GaN light emitting diodes (LEDs) in the shape of cuboids and circular disks
      have been fabricated by laser micromachining. The proposed circular geometry
      serves to enhance overall light extraction on a macro-scale and to improve
      uniformity of the emission pattern due to the rotational symmetry of the chip.
      Analysis of the chip shaping effect is carried out by ray-tracing simulations and
      further supported with mathematical modeling using ideal LED models, and
      subsequently verified with fabricated devices. In comparison, a 10% improvement
      in overall emission was observed for circular LEDs over the regular cuboids,
      consistent with simulations and calculations. The measured emission pattern from
      the circular LED confirms the axial symmetry of the emission beam.

PMID- 20052156
TI  - Polarization measurements through space-to-ground atmospheric propagation paths
      by using a highly polarized laser source in space.
AB  - The polarization characteristics of an artificial laser source in space were
      measured through space-to-ground atmospheric transmission paths. An existing
      Japanese laser communication satellite and optical ground station were used to
      measure Stokes parameters and the degree of polarization of the laser beam
      transmitted from the satellite. As a result, the polarization was preserved
      within an rms error of 1.6 degrees, and the degree of polarization was 99.4+/
      4.4% through the space-to-ground atmosphere. These results contribute to the link
      estimation for quantum key distribution via space and provide the potential for
      enhancements in quantum cryptography worldwide in the future.

PMID- 20052155
TI  - High throughput transmission optical projection tomography using low cost
      graphics processing unit.
AB  - We implement the use of a graphics processing unit (GPU) in order to achieve real
      time data processing for high-throughput transmission optical projection
      tomography imaging. By implementing the GPU we have obtained a 300 fold
      performance enhancement in comparison to a CPU workstation implementation. This
      enables to obtain on-the-fly reconstructions enabling for high throughput
      imaging.

PMID- 20052157
TI  - Optical monitoring of oxygen tension in cortical microvessels with confocal
      microscopy.
AB  - Evaluating cerebral oxygenation is of critical importance for the understanding
      of brain function and several neuropathologies. Although several techniques exist
      for measuring cerebral oxygenation in vivo, the most widely accepted techniques
      offer limited spatial resolution. We have developed a confocal imaging system for
      minimally invasive measurement of oxygen tension (pO(2)) in cerebral microvessels
      with high spatial and temporal resolution. The system relies on the
      phosphorescence quenching method using exogenous porphyrin-based dendritic oxygen
      probes. Here we present high-resolution phosphorescence images of cortical
      microvasculature and temporal pO(2) profiles from multiple locations in response
      to varied fraction of inspired oxygen and functional activation.

PMID- 20052158
TI  - Nanoscale residual stress-field mappingaround nanoindents in SiCby IR s-SNOM and
      confocal Raman microscopy.
AB  - We map a nanoindent in a silicon carbide (SiC) crystal by infrared (IR)
      scattering-type scanning near-field optical microscopy (s-SNOM) and confocal
      Raman microscopy and interpret the resulting images in terms of local residual
      stress-fields. By comparing near-field IR and confocal Raman images, we find that
      the stress-induced shifts of the longitudinal optical phonon-frequencies (LO) and
      the related shift of the phonon-polariton near-field resonance give rise to Raman
      and s-SNOM image contrasts, respectively. We apply single-frequency IR s-SNOM for
      nanoscale resolved imaging of local stress-fields and confocal Raman microscopy
      to obtain the complete spectral information about stress-induced shifts of the
      phonon frequencies at diffraction limited spatial resolution. The spatial
      extension of the local stress-field around the nanoindent agrees well between
      both techniques. Our results demonstrate that both methods ideally complement
      each other, allowing for the detailed analysis of stress-fields at e.g. material
      and grain boundaries, in Micro-Electro-Mechanical-Systems (MEMS), or in
      engineered nanostructures.

PMID- 20052159
TI  - Preservation of the carrier envelope phase during cross-polarized wave
      generation.
AB  - The preservation of carrier envelope phase (CEP) during Cross-Polarized Wave
      Generation (XPWG) is demonstrated through two independent experiments based on
      the spatially and spectrally resolved interference fringes formed by the XPW beam
      and its fundamental. In a first measurement, we found that the vertical fringe
      position on the spatial detector was maintained over many consecutive laser
      shots, implying practically no change in relative CEP between the XPW and the
      fundamental. In a second experiment, we measured the change in relative CEP
      between the XPW and fundamental beam by systematically varying the amount of
      material dispersion inside the XPW arm of the interferometer. The recorded rate
      of relative phase change was in excellent agreement with the theoretical value.

PMID- 20052160
TI  - Partially coherent standard and elegant Laguerre-Gaussian beams of all orders.
AB  - Partially coherent standard and elegant Laguerre-Gaussian (LG) beams of all
      orders are introduced as a natural extension of coherent standard and elegant LG
      beams to the stochastic domain. By expanding the LG modes into a finite sum of
      Hermite-Gaussian modes, the analytical formulae are obtained for the cross
      spectral densities of partially coherent standard and elegant LG beams in the
      source plane and after passing through paraxial ABCD optical system, based on the
      generalized Collins integral formula. A comparative study of the propagation
      properties of the partially coherent standard and elegant LG beams in free space
      is carried out via a set of numerical examples. Our results indicate that the
      intensity and spreading properties of partially coherent standard and elegant LG
      beams are closely related to their initial coherence states, and are very
      different from the corresponding results for the coherent standard and elegant LG
      beams. In particular, an elegant LG beam spreads slower than a standard LG beam,
      while this advantage disappears when their initial coherences are very small. Our
      results may find applications in connection with laser beam shaping, singular
      optics and astrophysical measurements of angular momentum of radiation.

PMID- 20052161
TI  - Imaging visible light using anisotropic metamaterial slab lens.
AB  - It has been shown that an anisotropic metamaterial made of nanowire array can
      realize negative refraction of light even without a negative phase index of
      refraction. Such non-resonant bulk material can be fabricated by bottom-up
      electrochemical method. Using this material, we were able to achieve lensing
      action with micron-thick slab and demonstrate imaging of a slit object. The
      details of the focused light beam in 3-dimensional space have been mapped with
      near field scanning optical microscope (NSOM).

PMID- 20052162
TI  - All-optical and polarization-independent spatial filter based on a vertically
      aligned polymer-stabilized liquid crystal film with a photoconductive layer.
AB  - An all-optical and polarization-independent spatial filter was developed in a
      vertically-aligned (VA) polymer-stabilized liquid crystal (PSLC) film with a
      photoconductive (PC) layer. This spatial filter is based on the effect of light
      on the conductivity of PC layer: high (low)-intensity light makes the
      conductivity of the PC layer high (low), resulting in a low (high) threshold
      voltage of the PC-coated VA PSLC cell. Experimental results indicate that this
      spatial filter is a high-pass filter with low optical-power consumption (about
      1.11 mW/cm(2)) in an optical Fourier transform system. The high-pass
      characteristic was confirmed by simulation. Accordingly, the all-optical and
      polarization-independent spatial filter can be used to enhance the edges of
      images.

PMID- 20052163
TI  - Fabrication and characterization of chalcogenide glass photonic crystal
      waveguides.
AB  - We report on the fabrication of chalcogenide glass (Ag-As(2)Se(3)) photonic
      crystal waveguides and the first detailed characterization of the linear and
      nonlinear optical properties. The waveguides, fabricated by e-beam lithography
      and ICP etching exhibit typical transmission spectra of photonic crystal
      waveguides, and exhibit high optical nonlinearity. Nonlinear phase shift of 1.5pi
      through self-phase modulation is observed at 0.78 W input peak power in a 400
      microm long device. The effective nonlinear parameter gamma(eff) estimated from
      this result reaches 2.6 x 10(4) W(-1)m(-1). Four-wave mixing is also observed in
      the waveguide, while two-photon absorption at optical communication wavelengths
      is sufficiently small and the corresponding figure of merit is larger than 11.

PMID- 20052164
TI  - Numerical and experimental investigation of dissipative solitons in passively
      mode-locked fiber lasers with large net-normal-dispersion and high nonlinearity.
AB  - Dissipative soliton evolution in passively mode-locked fiber lasers with large
      net-normal-dispersion and high nonlinearity is investigated numerically and
      confirmed experimentally. I have proposed a theoretical model including the
      nonlinear polarization evolution and spectral filtering effect. This model
      successfully predicts the pulse behaviors of the proposed laser, such as the
      multi-soliton evolution, quasi-rectangle-spectrum profile, trapezoid-spectrum
      profile, and unstable state. Numerical results show that, in contrast to the
      typical net- or all-normal-dispersion fiber lasers with the slight variation of
      the pulse breathing, the breathing ratios of the pulse duration and spectral
      width of our laser are more than three and two during the intra-cavity
      propagation, respectively. The nonlinear polarization rotation mechanism together
      with spectral filtering effect plays the key roles on the pulse evolution. The
      experimental observations confirm the theoretical predictions.

PMID- 20052165
TI  - Ultrafast laser inscribed Yb:KGd(WO4)2 and Yb:KY(WO4)2 channel waveguide lasers.
AB  - We demonstrate laser action in diode-pumped microchip monolithic cavity channel
      waveguides of Yb:KGd(WO(4))(2) and Yb:KY(WO(4))(2) that were fabricated by
      ultrafast laser writing. The maximum output power achieved was 18.6 mW with a
      threshold of approximately 100 mW from an Yb:KGd(WO(4))(2) waveguide laser
      operating at 1023 nm. The propagation losses for this waveguide structure were
      measured to be 1.9 dBcm(-1).

PMID- 20052166
TI  - Design of a high-sensor count fibre optic manometry catheter for in-vivo colonic
      diagnostics.
AB  - The design of a fibre Bragg grating based manometry catheter for in-vivo
      diagnostics in the human colon is presented. The design is based on a device
      initially developed for use in the oesophagus, but in this instance, longer
      sensing lengths and increased flexibility were required to facilitate
      colonoscopic placement of the device and to allow access to the convoluted
      regions of this complex organ. The catheter design adopted allows the number of
      sensing regions to be increased to cover extended lengths of the colon whilst
      maintaining high flexibility and the close axial spacing necessary to accurately
      record pertinent features of peristalsis. Catheters with 72 sensing regions with
      an axial spacing of 1 cm have been assembled and used in-vivo to record
      peristaltic contractions in the human colon over a 24hr period. The close axial
      spacing of the pressure sensors has, for the first time, identified the complex
      nature of propagating sequences in both antegrade (towards the anus) and
      retrograde (away from the anus) directions in the colon. The potential to miss
      propagating sequences at wider sensor spacings is discussed and the resultant
      need for close axial spacing of sensors is proposed.

PMID- 20052167
TI  - Nonparaxial diffraction analysis of Airy and SAiry beams.
AB  - We theoretically analyze Airy beams by solving the exact vectorial Helmholtz
      equation using boundary conditions at a diffraction aperture. As result, the
      diffracted beams are obtained in the whole space; thus, we demonstrate that the
      parabolic trajectories are larger than those previously reported, showing that
      the Airy beams start to form before the Fourier plane. We also demonstrate the
      possibility of using a new type of Airy beams (SAiry beams) with finite energy
      that can be generated at the focal plane of the lens due to diffraction by a
      circular aperture of a spherical wave modified by a cubic phase. The finite
      energy ensured by the principle of conservation of energy of a diffracted beam.

PMID- 20052168
TI  - Non-trivial scaling of self-phase modulation and three-photon absorption in III-V
      photonic crystal waveguides.
AB  - We investigate the nonlinear response of photonic crystal waveguides with
      suppressed two-photon absorption. A moderate decrease of the group velocity
      (approximately c/6 to c/15, a factor of 2.5) results in a dramatic (x 30)
      enhancement of three-photon absorption well beyond the expected scaling,
      proportional, variant 1/v3g. This non-trivial scaling of the effective nonlinear
      coefficients results from pulse compression, which further enhances the optical
      field beyond that of purely slow-group velocity interactions. These observations
      are enabled in mm-long slow-light photonic crystal waveguides owing to the strong
      anomalous group-velocity dispersion and positive chirp. Our numerical physical
      model matches measurements remarkably.

PMID- 20052169
TI  - Epitaxial quantum dots in stretchable optical microcavities.
AB  - Arrays of GaAs microring optical resonators with embedded InGaAs quantum dots
      (QDs) are placed on top of Pb(Mg(1/3)Nb(2/3))O(3)-PbTiO(3) piezoelectric
      actuators, which allow the microcavities to be reversibly "stretched" or
      "squeezed" by applying relatively large biaxial stresses at low temperatures. The
      emission energy of both QDs and optical modes red- or blue- shift depending on
      the strain sign, with the QD emission shifting more rapidly than the optical mode
      with applied strain. The QD energy shifts are used to estimate the strain in the
      structures based on linear deformation potential theory and the finite element
      method. The shift of the modes is attributed to both the physical deformation and
      the change in refractive index due to the photoelastic effect. Remarkably,
      excitonic emissions from different QDs are observed to shift at different rates,
      implying that this technique can be used to bring spatially separated excitons
      into resonance.

PMID- 20052170
TI  - Security enhanced optical encryption system by random phase key and permutation
      key.
AB  - Conventional double random phase encoding (DRPE) encrypts plaintext to white
      noise-like ciphertext which may attract attention of eavesdroppers, and recent
      research reported that DRPE is vulnerable to various attacks. Here we propose a
      security enhanced optical encryption system that can hide the existence of secret
      information by watermarking. The plaintext is encrypted using iterative
      fractional Fourier transform with random phase key, and ciphertext is randomly
      permuted with permutation key before watermarking. Cryptanalysis shows that
      linearity of the security system has been broken and the permutation key prevent
      the attacker from accessing the ciphertext in various attacks. A series of
      simulations have shown the effectiveness of this system and the security strength
      is enhanced for invisibility, nonlinearity and resistance against attacks.

PMID- 20052171
TI  - Cryogenic spectroscopy of ultra-low density colloidal lead chalcogenide quantum
      dots on chip-scale optical cavities towards single quantum dot near-infrared
      cavity QED.
AB  - We present evidence of cavity quantum electrodynamics from a sparse density of
      strongly quantum-confined Pb-chalcogenide nanocrystals (between 1 and 10)
      approaching single-dot levels on moderately high-Q mesoscopic silicon optical
      cavities. Operating at important near-infrared (1500-nm) wavelengths, large
      enhancements are observed from devices and strong modifications of the QD
      emission are achieved. Saturation spectroscopy of coupled QDs is observed at 77K,
      highlighting the modified nanocrystal dynamics for quantum information
      processing.

PMID- 20052172
TI  - Low Vpp, ultralow-energy, compact, high-speed silicon electro-optic modulator.
AB  - We present a high-speed silicon optical modulator with a low V(pp) (peak-to-peak
      driving voltage) and ultralow energy consumption based on a microring resonator,
      with the refractive index modulation achieved by electric-field-induced carrier
      depletion in a reverse-biased lateral pn diode embedded in the ring structure.
      With a V(pp) of 2 V, we demonstrate a silicon modulator with a 3 dB bandwidth of
      11 GHz, a modulation depth of 6.5 dB together with an insertion loss of 2 dB,
      ultralow energy consumption of 50 fJ per bit, and a small device active area of
      approximately 1000 microm(2).

PMID- 20052173
TI  - Dark Hanle resonances from selected segments of the Gaussian laser beam cross
      section.
AB  - We present the Hanle EIT resonances obtained from the various segments of the
      Gaussian laser beam cross-section, selected by moving the small aperture (placed
      in front of the detector) radially along the laser beam. Significant differences
      in the Hanle lineshapes are observed depending on whether the central or outer
      parts of the Gaussian laser beam are detected. The line narrowing and two counter
      sign peaks occur at outer, less intense parts of the beam. The theoretical model
      suggests that the EIT lineshapes in the laser wings are result of the
      interference of the laser light and coherently prepared atoms coming from the
      central part of the beam. By blocking the central part of the laser beam in front
      of the detector, narrower, and for high laser intensities, even more contrasted
      Hanle resonances are obtained.

PMID- 20052174
TI  - An 88 fs fiber soliton laser using a quantum well saturable absorber with an
      ultrafast intersubband transition.
AB  - We demonstrate a 1.5 microm passively mode-locked fiber laser using an
      intersubband transition (ISBT) in a quantum well as a saturable absorber. The
      saturable absorption characteristic of faster than 1 ps in the ISBT was utilized
      for femtosecond pulse generation. We designed the laser cavity as a soliton
      laser, which enabled us to generate a stable pulse. As a result, an 88 fs, 42 MHz
      soliton pulse was successfully generated.

PMID- 20052175
TI  - Low power and fast electro-optic silicon modulator with lateral p-i-n embedded
      photonic crystal nanocavity.
AB  - We have fabricated high-Q photonic crystal nanocavities with a lateral p-i-n
      structure to demonstrate low-power and high-speed electro-optic modulation in a
      silicon chip. GHz operation is demonstrated at a very low (microW level)
      operating power, which is about 4.6 times lower than that reported for other
      cavities in silicon. This low-power operation is due to the small size and high-Q
      of the photonic crystal nanocavity.

PMID- 20052176
TI  - Fabrication and optical properties of Y2O3: Eu3+ nanofibers prepared by
      electrospinning.
AB  - Y(2)O(3): Eu(3+) nanofibers with the average diameter of ~300 nm were in situ
      fabricated by electrospinning. X-ray diffraction (XRD) pattern confirmed that the
      Y(2)O(3): Eu(3+) nanofibers were composed of pure body-centered cubic (bcc)
      Y(2)O(3) phase. High-resolution transmission electron microscopy (HRTEM) results
      indicated that Y(2)O(3): Eu(3+) nanofibers were constituted of nonspherical
      crystalline grains, and these crystalline grains were orderly arranged along the
      axial direction of single nanofiber. These Y(2)O(3): Eu(3+) nanofibers showed a
      partially polarized photoluminescence (PL). The arrangement of crystalline grains
      and the mismatch of dielectric constant between Y(2)O(3): Eu(3+) nanofiber and
      its environment probably contributed together to the polarized PL from Y(2)O(3):
      Eu(3+) nanofiber.

PMID- 20052177
TI  - White light Sagnac interferometer for snapshot linear polarimetric imaging.
AB  - The theoretical and experimental demonstration of a dispersion-compensated
      polarization Sagnac interferometer (DCPSI) is presented. An application of the
      system is demonstrated by substituting the uniaxial crystal-based Savart plate
      (SP) in K. Oka's original snapshot polarimeter implementation with a DCPSI. The
      DCPSI enables the generation of an achromatic fringe field in white-light,
      yielding significantly more radiative throughput than the original quasi
      monochromatic SP polarimeter. Additionally, this interferometric approach offers
      an alternative to the crystal SP, enabling the use of standard reflective or
      transmissive materials. Advantages are anticipated to be greatest in the thermal
      infrared, where uniaxial crystals are rare and the at-sensor radiance is often
      low when compared to the visible spectrum. First, the theoretical operating
      principles of the Savart plate polarimeter and a standard polarization Sagnac
      interferometer polarimeter are provided. This is followed by the theoretical and
      experimental development of the DCPSI, created through the use of two blazed
      diffraction gratings. Outdoor testing of the DCPSI is also performed,
      demonstrating the ability to detect either the S(2) and S(3), or the S(1) and
      S(2) Stokes parameters in white-light.

PMID- 20052178
TI  - Polarization-dependent GaN surface grating reflector for short wavelength
      applications.
AB  - This study proposes a one-dimensional sub-wavelength grating structure on GaN
      surface which behaves as a reflector for transverse-electric polarized light in
      the blue wavelength range. The rigorous coupled-wave analysis method was used to
      analyze the effects of various structural parameters on the reflectance spectra
      of the grating. Based on the optimal design, a GaN surface grating reflector
      (SGR) was fabricated using holographic lithography and dry etching processes. It
      showed reflectance that exceeded 90% over a 60-nm bandwidth. The obtained
      experimental results were in good agreement with simulated ones. The SGR has an
      advantage of structural simplicity, which should greatly facilitate the
      fabrication and integration of high reflectors on GaN-based short-wavelength
      photonic devices.

PMID- 20052179
TI  - Thin film Ag superlens towards lab-on-a-chip integration.
AB  - A thin metal film near-field superlens, as originally suggested by Pendry and
      realized by Fang et al. and Melville et al., is investigated with emphasis on
      materials suitable for integration on a lab-on-a-chip platform. A chemically
      resistant cyclo-olefin copolymer (COC), mr-I-T85 from microresist technology, is
      applied as dielectric matrix/spacer for an Ag thin film superlens. The superlens
      successfully resolves 80 nm half-pitch gratings when illuminated with UV
      radiation at a free space wavelength of 365 nm. The superlens design, fabrication
      and characterization is discussed.

PMID- 20052180
TI  - Radio-frequency waveform generator with time-multiplexing capabilities based on
      multi-wavelength pulse compression.
AB  - We demonstrate a new photonically assisted reconfigurable radio-frequency
      waveform generator. The setup is based on phase modulating a multi-wavelength
      pulse source and subsequent compression in a dispersive medium. Under the
      appropriate conditions, we show that the photodetected electrical signal is
      broadband and coherent. Specifically, we show that this system allows for the
      synthesis of a reconfigurable finite-impulse-response filter where the number of
      filter taps is given by the number of wavelengths available from the multi
      wavelength source and the reconfiguration is determined simply by their power and
      wavelength separation. We also show that this technique allows for time
      multiplexing the synthesized waveforms, thus leading to an effective switching
      speed fixed by the clock rate. In particular, we show transitions between
      synthesized waveforms with a frequency content > 60 GHz in periods shorter than
      100 ps.

PMID- 20052181
TI  - Above threshold spectral dependence of linewidth enhancement factor, optical
      duration and linear chirp of quantum dot lasers.
AB  - The spectral dependence of the linewidth enhancement factor above threshold is
      experimentally observed from a quantum dot Fabry-Perot semiconductor laser. The
      linewidth enhancement factor is found to be reduced when the quantum dot laser
      operates approximately 10 nm offset to either side of the gain peak. It becomes
      significantly reduced on the anti-Stokes side as compared to the Stokes side. It
      is also found that the temporal duration of the optical pulses generated from
      quantum dot mode-locked lasers is shorter when the laser operates away from the
      gain peak. In addition, less linear chirp is impressed on the pulse train
      generated from the anti-Stokes side whereas the pulses generated from the gain
      peak and Stokes side possess a large linear chirp. These experimental results
      imply that enhanced performance characteristics of quantum dot lasers can be
      achieved by operating on the anti-Stokes side, approximately 10 nm away from the
      gain peak.

PMID- 20052182
TI  - Efficient fiber coupler for vertical silicon slot waveguides.
AB  - A mode size converter for efficient fiber coupling to silicon slot waveguides was
      proposed and demonstrated. It consists of two inverted lateral tapers that extend
      from the two strips of the silicon slot waveguide, and an overlaid low index
      waveguide with expanded mode size. Parameters including taper length and taper
      tip width were optimized with computer simulations. Samples were fabricated with
      a combined electron beam and photolithography process on a silicon-on-insulator
      wafer. The measured coupling loss to a standard single mode optical fiber was
      reduced by 8 dB for TE mode and 5.2 dB for TM mode with the converter.

PMID- 20052183
TI  - Narrow-line, cw orange light generation in a diode-pumped Nd:YVO4 laser using
      volume Bragg gratings.
AB  - We report on the demonstration of a narrow-line, cw orange 593-nm laser achieved
      via intracavity sum-frequency generation (SFG) of a diode-pumped dual-wavelength
      (1064 and 1342 nm) Nd:YVO(4) laser using two volume Bragg grating (VBG)
      reflectors. At diode pump power of up to 3.6 W, the 593-nm intracavity SFG laser
      radiates at the single longitudinal mode of spectral linewidth as narrow as
      approximately 15 MHz. More than 23-mW single-longitudinal-mode or 40-mW, <8.5-GHz
      (10-pm) linewidth (at 4.2-W diode pump power) 593-nm orange lights can be
      obtained from this compact laser system. Spectral tuning of the orange light was
      performed via the temperature tuning of the two VBGs in this system, achieving an
      effective tuning rate of ~5 pm/degrees C.

PMID- 20052184
TI  - Investigation of electrooptic modulator disruption by microwave-induced
      transients.
AB  - This paper presents a detailed investigation of the physical mechanisms
      underlying the disruption of a lithium niobate electrooptic modulator by RF
      pulses. It is shown that short-term modulator disruption is a direct consequence
      of resistive heating within the metal conductor of the coplanar waveguide
      electrode, which leads to a thermo-optic optical phase shift in the waveguides of
      the modulator. Resistive heating is also shown to contribute to permanent
      modulator damage at higher RF power. These results indicate that short-term RF
      disruption, and possibly RF damage, can be mitigated through improved thermal
      management. They also predict that short-term photonic link disruption can be
      reduced, if not eliminated, by use of a phase modulated photonic link.

PMID- 20052185
TI  - Revolution analysis of three-dimensional arbitrary cloaks.
AB  - We extend the design of radially symmetric three-dimensional invisibility cloaks
      through transformation optics to cloaks with a surface of revolution. We derive
      the expression of the transformation matrix and show that one of its eigenvalues
      vanishes on the inner boundary of the cloaks, while the other two remain strictly
      positive and bounded. The validity of our approach is confirmed by finite edge
      elements computations for a non-convex cloak of varying thickness.

PMID- 20052186
TI  - Second harmonic generation in gallium phosphide photonic crystal nanocavities
      with ultralow continuous wave pump power.
AB  - We demonstrate second harmonic generation in photonic crystal nanocavities
      fabricated in the semiconductor gallium phosphide. We observe second harmonic
      radiation at 750 nm with input powers of only nanowatts coupled to the cavity and
      conversion effciency P(out)/P(2)(in,coupled)=430%/W. The large electronic band
      gap of GaP minimizes absorption loss, allowing effcient conversion. Our results
      are promising for integrated, low-power light sources and on-chip reduction of
      input power in other nonlinear processes.

PMID- 20052187
TI  - Band-tunable color cone lasing emission based on dye-doped cholesteric liquid
      crystals with various pitches and a pitch gradient.
AB  - This study elucidates, for the first time, a novel band-tunable color cone lasing
      emission (CCLE) based on dye-doped cholesteric liquid crystal (DDCLC) films with
      various pitches. For several CLC cells with different pitches it was shown
      experimentally that the lasing band on the CCLE can be tuned among various color
      regions measured within different angular ranges. Some important features of the
      tunable CCLE are also identified and discussed. A spatially band-tunable color
      cone laser, based on a single DDCLC with a gradient pitch, is developed as a real
      application.

PMID- 20052188
TI  - Analytical coherency matrix treatment of shear strained fiber Bragg gratings.
AB  - Reconstruction of the strain tensor at the position of an embedded fiber Bragg
      grating sensor has been the goal of recent research. However, ambiguities in the
      measurand--the polarization resolved reflected intensity spectrum--upon
      occurrence of shear strain hinder its achievement due to lack of an invertible
      model. In this work, we derive such a model using coherency matrix properties of
      unpolarized light. We deduce simplified sensor parameters for the ambiguous shear
      strain loading case, which possibly lead to a practical inversion of the problem.

PMID- 20052189
TI  - A route to sub-diffraction-limited CARS Microscopy.
AB  - We theoretically investigate a scheme to obtain sub-diffraction-limited
      resolution in coherent anti-Stokes Raman scattering (CARS) microscopy. We find
      using density matrix calculations that the rise of vibrational (Raman) coherence
      can be strongly suppressed, and thereby the emission of CARS signals can be
      significantly reduced, when pre-populating the corresponding vibrational state
      through an incoherent process. The effectiveness of pre-populating the
      vibrational state of interest is investigated by considering the excitation of a
      neighbouring vibrational (control) state through an intense, mid-infrared control
      laser. We observe that, similar to the processes employed in stimulated emission
      depletion microscopy, the CARS signal exhibits saturation behaviour if the
      transition rate between the vibrational and the control state is large. Our
      approach opens up the possibility of achieving chemically selectivity sub
      diffraction-limited spatially resolved imaging.

PMID- 20052190
TI  - Regenerative properties of interferometricall-optical DPSK wavelength converters.
AB  - We discuss an all-optical DPSK wavelength conversion scheme comprising a delay
      interferometer demodulation stage followed by a Mach-Zehnder interferometer, the
      arms of which are formed by nonlinear waveguides. If operated properly, the
      configuration shows regenerative behaviour. This is true for nonlinear waveguides
      with a dominant cross-gain nonlinearity (e. g., for an electro-absorption
      amplitude modulator) as well as for the case of a dominant cross-phase
      nonlinearity (e. g., for Kerr effect based phase modulator). In addition, we show
      that nonlinear materials exhibiting cross-gain modulation properties can provide
      a binary phase response so far only known from the transfer functions of digital
      electronics.

PMID- 20052191
TI  - Electro-activation and electro-morphing of photorefractive funnel waveguides.
AB  - We demonstrate the electro-activation of funnel waveguides through the quadratic
      electro-optic effect in paraelectric potassiumlithium- tantalate-niobate. This
      allows us to achieve electro-optic intensity modulation in a single optical beam,
      a 1x2 switch, and finally the electrically controlled morphing of a single
      waveguide into a 1x2 and a 1x4 divider.

PMID- 20052192
TI  - Gain guiding in large-core Bragg fibers.
AB  - We theoretically analyze gain guiding in large-core Bragg fibers, to be used for
      large-mode-area laser amplifiers with single-transverse-mode operation. The
      signal is gain-guided in a low-index core, whereas the pump is guided by the
      photonic bandgap of the Bragg cladding to achieve good confinement. The high
      index layers in the Bragg cladding are half-wave thick at the signal wavelength
      in order to eliminate Bragg reflection, reducing the Bragg fiber effectively to a
      step-index fiber for gain guiding.

PMID- 20052193
TI  - Substitution of oxygen by fluorine in the GdSr2AlO5:Ce3+ phosphors: Gd1
      xSr2+xAlO5-xFx solid solutions for solid state white lighting.
AB  - Solid solutions between two isotypic host compounds: GdSr(2)AlO(5) and
      Sr(3)AlO(4)F; Gd(1-x)Sr(2+x)AlO(5-x)F(x):Ce(3+) (GSAF:Ce(3+)), have been prepared
      across the complete solid solution range x. Depending on x, the series display
      considerable optical tunability of emission wavelengths in the range 574 nm to
      474 nm, which is attributed to the decreased crystal field splitting arising from
      increased host ionicity with fluorine addition. Applying the GSAF:Ce(3+)
      phosphors on InGaN LEDs (lambda (max) = 405 nm and 450 nm) permits white lighting
      sources to be prepared. The characteristics of these are reported.

PMID- 20052194
TI  - A novel reconfigurable optical interconnect architecture using an Opto-VLSI
      processor and a 4-f imaging system.
AB  - A novel reconfigurable optical interconnect architecture for on-board high-speed
      data transmission is proposed and experimentally demonstrated. The interconnect
      architecture is based on the use of an Opto-VLSI processor in conjunction with a
      4-f imaging system to achieve reconfigurable chip-to-chip or board-to-board data
      communications. By reconfiguring the phase hologram of an Opto-VLSI processor,
      optical data generated by a vertical Cavity Surface Emitting Laser (VCSEL)
      associated to a chip (or a board) is arbitrarily steered to the photodetector
      associated to another chip (or another board). Experimental results show that the
      optical interconnect losses range from 5.8dB to 9.6dB, and that the maximum
      crosstalk level is below -36dB. The proposed architecture is tested for high
      speed data transmission, and measured eye diagrams display good eye opening for
      data rate of up to 10Gb/s.

PMID- 20052195
TI  - Broadband frequency conversion and shaping of single photons emitted from a
      nonlinear cavity.
AB  - Much recent effort has focused on coupling individual quantum emitters to optical
      microcavities in order to produce single photons on demand, enable single-photon
      optical switching, and implement functional nodes of a quantum network.
      Techniques to control the bandwidth and frequency of the outgoing single photons
      are of practical importance, allowing direct emission into telecommunications
      wavelengths and "hybrid" quantum networks incorporating different emitters. Here,
      we describe an integrated approach involving a quantum emitter coupled to a
      nonlinear optical resonator, in which the emission wavelength and pulse shape are
      controlled using the intra-cavity nonlinearity. Our scheme is general in nature,
      and demonstrates how the photonic environment of a quantum emitter can be
      tailored to determine the emission properties. As specific examples, we discuss a
      high Q-factor, TE-TM double-mode photonic crystal cavity design that allows for
      direct generation of single photons at telecom wavelengths (1425 nm) starting
      from an InAs/GaAs quantum dot with a 950 nm transition wavelength, and a scheme
      for direct optical coupling between such a quantum dot and a diamond nitrogen
      vacancy center at 637 nm.

PMID- 20052197
TI  - Increasing trap stiffness with position clamping in holographic optical tweezers.
AB  - We present a holographic optical tweezers system capable of position clamping
      multiple particles. Moving an optical trap in response to the trapped object's
      motion is a powerful technique for optical control and force measurement. We have
      now realised this experimentally using a Boulder Nonlinear Systems Spatial Light
      Modulator (SLM) with a refresh rate of 203Hz. We obtain a reduction of 44% in the
      variance of the bead's position, corresponding to an increase in effective trap
      stiffness of 77%. This reduction relies on the generation of holograms at high
      speed. We present software capable of calculating holograms in under 1ms using a
      graphics processor unit.

PMID- 20052196
TI  - Polarization maintaining fiber based ultra-high resolution spectral domain
      polarization sensitive optical coherence tomography.
AB  - We present a new ultra high resolution spectral domain polarization sensitive
      optical coherence tomography (PS-OCT) system based on polarization maintaining
      (PM) fibers. The method transfers the principles of our previous bulk optic PS
      OCT systems to a fiberized setup. The phase shift between the orthogonal
      polarization states travelling in the two orthogonal modes of the PM fiber is
      compensated by software in post processing. Thereby, the main advantage of our
      bulk optics setups, i.e. the use of only a single input polarization state to
      simultaneously acquire reflectivity, retardation, optic axis orientation, and
      Stokes vector, is maintained. The use of a broadband light source of 110 nm
      bandwidth provides improved depth resolution and smaller speckle size. The latter
      is important for improved resolution of depolarization imaging. We demonstrate
      our instrument for high-resolution PS-OCT imaging of the healthy human retina.

PMID- 20052198
TI  - Modulation of evanescent focus by localized surface plasmons waveguide.
AB  - In this paper, we present the modulation of a tightly focused evanescent field by
      a nano-plasmonic waveguide, which consists of two silver nanorods lying on the
      interface of two dielectric media. Linearly polarized and radially polarized
      illuminating beams are investigated under the influence of localized surface
      plasmons effect. It is demonstrated that different polarization components of the
      tightly focused evanescent field can be modulated accordingly. The results
      obtained from the finite difference time domain simulation show that super
      resolved focal spot can be achieved using the nano-plasmonic waveguide structure.

PMID- 20052199
TI  - In vivo real-time recording of UV-induced changes in the autofluorescence of a
      melanin-containing fungus using a micro-spectrofluorimeter and a low-cost webcam.
AB  - An optical epifluorescence microscope, coupled to a CCD camera, a standard webcam
      and a microspectrofluorimeter, are used to record in vivo real-time changes in
      the autofluorescence of spores and hyphae in Aspergillus niger, a fungus
      containing melanin, while exposed to UV irradiation. The results point out major
      changes in both signal intensity and the spectral shape of the autofluorescence
      signal after only few minutes of exposure, and can contribute to the
      interpretation of data obtained with other fluorescence techniques, including
      those, such as GPF labeling, in which endogenous fluorophores constitute a major
      disturbance.

PMID- 20052200
TI  - A method to unmix multiple fluorophores in microscopy images with minimal a
      priori information.
AB  - The ability to quantify the fluorescence signals from multiply labeled biological
      samples is highly desirable in the life sciences but often difficult, because of
      spectral overlap between fluorescent species and the presence of
      autofluorescence. Several so called unmixing algorithms have been developed to
      address this problem. Here, we present a novel algorithm that combines
      measurements of lifetime and spectrum to achieve unmixing without a priori
      information on the spectral properties of the fluorophore labels. The only
      assumption made is that the lifetimes of the fluorophores differ. Our method
      combines global analysis for a measurement of lifetime distributions with
      singular value decomposition to recover individual fluorescence spectra. We
      demonstrate the technique on simulated datasets and subsequently by an experiment
      on a biological sample. The method is computationally efficient and
      straightforward to implement. Applications range from histopathology of complex
      and multiply labelled samples to functional imaging in live cells.

PMID- 20052201
TI  - High energy cw-diode pumped Nd:YVO4 regenerative amplifier with efficient second
      harmonic generation.
AB  - We report on a 888 nm diode-pumped Nd:YVO4 regenerative amplifier with up to 33.7
      W output power with a repetition-rate of 20 kHz and an adjustable pulse duration
      between 217 ps and 1 ns. This setup allowed for efficient second harmonic
      generation with an efficiency of up to 79%.

PMID- 20052202
TI  - A high performance photonic pulse processing device.
AB  - This paper presents an all optical fiber based implementation of a hybrid analog
      digital computational primitive that provides a basis for complex processing on
      high bandwidth signals. A natural implementation of a hybrid analog/digital
      photonic processing primitive is achieved through the integration of new
      nonlinear fiber, and exploitation of the physics of semiconductor device to
      process signals in unique ways. Specifically, we describe the use of a
      semiconductor optical amplifier to implement leaky temporal integration of a
      signal and a highly Ge-doped nonlinear fiber for thresholding. A straightforward
      correspondence between our computational primitive and leaky-integrate-and-fire
      neurons permits leveraging of a large body of research characterizing the
      computational capabilities of these devices and the emerging pulse processing
      computational paradigm as a means to implement practical signal processing
      algorithms in hybrid computing platforms. An experimental demonstration of the
      behavior of the pulse processing primitive is presented.

PMID- 20052203
TI  - Narrowband multilayer coatings for the extreme ultraviolet range of 50-92 nm.
AB  - A new type of multilayer coatings with narrowband reflection properties and
      peaked in the approximately 50- 92 nm spectral range has been developed.
      Multilayers are based on Yb, Al, and SiO films and they have been prepared by
      thermal evaporation. Efficient multilayers based on Yb and Al, with an SiO
      protective layer were prepared, but they developed a dendrite structure, which
      was attributed to the reactivity between Al and Yb. Multilayers based on Yb and
      Al, with both SiO protective and barrier layers, resulted in efficient reflective
      filters, with no observable dendrite growth. The peak reflectance of aged
      multilayers was of the order of approximately 0.20, with bandwidths in the range
      of 12 to 22 nm FWHM.

PMID- 20052204
TI  - Compact second-harmonic generation laser module with 1 W optical output power at
      490 nm.
AB  - We demonstrate continues-wave 1 W at 490 nm on a 2.5 cm(3) micro-optical bench
      using single-path second-harmonic generation with a periodically poled
      MgO:LiNbO(3) bulk crystal. The pump laser is a distributed Bragg reflector
      tapered diode laser having a single-frequency spectrum and a pump power of 9.5 W.
      Based on that 1 W blue light could be achieved resulting in an optical conversion
      efficiency of 11%. Furthermore, the module has an output power stability of
      better than 2% and the blue laser beam shows an nearly diffraction limited beam
      quality of M(2)(sigma) = 1.2 in vertical and M(2)(sigma) = 2 in lateral
      direction.

PMID- 20052205
TI  - Self-pumped phase conjugation of light beams carrying orbital angular momentum.
AB  - We investigate the properties of angular momentum carrying vortex beams,
      reflected by a phase-conjugating mirror. It is shown that a self-pumped
      photorefractive phase-conjugating mirror is suitable to produce stable, high
      fidelity phase conjugation of vortex beams. We prove that the topological charge
      of the vortex beam is maintained, and thus the angular momentum in the laboratory
      frame of reference is reversed, as it is expected by the time reversal property
      of the phase-conjugating mirror. The three dimensional interference pattern in
      front of the phase-conjugating mirror is studied and applications in optical
      traps are suggested.

PMID- 20052206
TI  - Design of wide-angle solar-selective absorbers using aperiodic metal-dielectric
      stacks.
AB  - Spectral control of the emissivity of surfaces is essential in applications such
      as solar thermal and thermophotovoltaic energy conversion in order to achieve the
      highest conversion efficiencies possible. We investigated the spectral
      performance of planar aperiodic metal-dielectric multilayer coatings for these
      applications. The response of the coatings was optimized for a target operational
      temperature using needle-optimization based on a transfer matrix approach.
      Excellent spectral selectivity was achieved over a wide angular range. These
      aperiodic metal-dielectric stacks have the potential to significantly increase
      the efficiency of thermophotovoltaic and solar thermal conversion systems.
      Optimal coatings for concentrated solar thermal conversion were modeled to have a
      thermal emissivity <7% at 720K while absorbing >94% of the incident light. In
      addition, optimized coatings for solar thermophotovoltaic applications were
      modeled to have thermal emissivity <16% at 1750K while absorbing >85% of the
      concentrated solar radiation.

PMID- 20052207
TI  - Fabrication of optical waveguides by imprinting: usage of positive tone resist as
      a mould for UV-curable polymer.
AB  - Optical ridge type waveguides based on UV-curable polymer were fabricated by
      imprinting method. Positive tone resist patterned on a silicon wafer was used as
      a mould. The characterization of waveguides was carried out by coupling TE
      polarized light from a tapered fiber into a waveguide with 30 mm length and
      mapping the intensity distribution with another tapered fiber at the output facet
      of a waveguide. Proper single- or multimode operation was observed depending on
      the waveguide width being either 2 microm or 6 microm. Experimental observations
      on the mode profiles were also supported by the simulation results. Average power
      transmissions of 32% at 1530 nm wavelength and 45% at 1310 nm wavelength were
      characterized. The results suggest that the simple mould fabrication process
      might be a useful technique for device prototyping and that the performance of
      replicated waveguides can meet the requirements for certain applications.

PMID- 20052208
TI  - Producing high fidelity single photons with optimal brightness via waveguided
      parametric down-conversion.
AB  - Parametric down-conversion (PDC) offers the possibility to control the
      fabrication of non-Gaussian states such as Fock states. However, in conventional
      PDC sources energy and momentum conservation introduce strict frequency and
      photon number correlations, which impact the fidelity of the prepared state. In
      our work we optimize the preparation of single-photon Fock states from the
      emission of waveguided PDC via spectral filtering. We study the effect of
      correlations via photon number resolving detection and quantum interference. Our
      measurements show how the reduction of mixedness due to filtering can be
      evaluated. Interfering the prepared photon with a coherent state we establish an
      experimentally measured fidelity of the produced target state of 78%.

PMID- 20052209
TI  - The effect of gain medium length on dynamic mode stability in semiconductor
      lasers with a long intra-cavity filter.
AB  - We investigate theoretically and experimentally the effect of the physical length
      of gain medium on dynamic mode stability in semiconductor lasers with an intra
      cavity filter. In simulation, two types of analysis models were used to examine
      the lasing properties and to analyze the dynamic mode stability of the external
      cavity system, respectively. In experiment, two different kinds of the structures
      were fabricated and their spectra were analyzed. Both simulation and measurement
      results show clearly the length of the gain medium has a critical influence on
      the stability around the peak wavelength of the filter.

PMID- 20052210
TI  - Rapid-scanning terahertz precision spectrometer with more than 6 THz spectral
      coverage.
AB  - We report a terahertz time-domain spectrometer with more than 6 THz spectral
      coverage and 1 GHz resolution based on high-speed asynchronous optical sampling.
      It operates at 2 kHz scan rate without mechanical delay stage. The frequency
      error of the system at 60 s acquisition time is determined by comparing a
      measured water vapor absorption spectrum to data reported in the HITRAN database.
      The mean error of 87 evaluated absorption lines is 142 MHz.

PMID- 20052211
TI  - Transient memory effect in the photoluminescence of InGaN single quantum wells.
AB  - The transition to maximum photoluminescence of InGaN single quantum wells is a
      phenomena that has time constants in the range of few seconds. Using a systematic
      illumination/darkening procedure we found that these characteristics are related
      to previous stimulations as if the sample has a memory of past illumination
      events. Choosing opportune time sequences, time constants were observed to vary
      more than 100%. These facts suggest the presence of carrier trapping/de-trapping
      processes that act beyond the single illumination event, accumulating over time
      in a complex effect.

PMID- 20052212
TI  - Coherent and collimated blue light generated by four-wave mixing in Rb vapour.
AB  - We investigate frequency up-conversion of low power cw resonant radiation in Rb
      vapour as a function of various experimental parameters. We present evidence that
      the process of four wave mixing is responsible for unidirectional blue light
      generation and that the phase matching conditions along a light-induced waveguide
      determine the direction and divergence of the blue light. Velocity-selective
      excitation to the 5D level via step-wise and two-photon processes results in a
      Doppler-free dependence on the frequency detuning of the applied laser fields
      from the respective dipole-allowed transitions. Possible schemes for ultraviolet
      generation are discussed.

PMID- 20052213
TI  - Ultra-rapid dispersion measurement in optical fibers.
AB  - We present a novel method to measure the chromatic dispersion of fibers with
      lengths of several kilometers. The technique is based on a rapidly swept Fourier
      domain mode locked laser driven at 50kHz repetition rate. Amplitude modulation
      with 400MHz and phase analysis yield the dispersion values over a 130nm
      continuous wavelength tuning range covering C and L band. The high acquisition
      speed of 10micros for individual wavelength-resolved traces Deltat(lambda) can
      reduce effects caused by thermal drift and acoustic vibrations. It enables real
      time monitoring with update rates >100Hz even when averaging several hundred
      acquisitions for improved accuracy.

PMID- 20052214
TI  - Multiplex coherent anti-Stokes Raman scattering (MCARS) for chemically sensitive,
      label-free flow cytometry.
AB  - Flow cytometry is an ever-advancing high-throughput multivariate analysis tool
      that natively provides size and morphological information. To obtain molecular
      information, however, typically requires the addition of fluorophores, which are
      limited by spectral overlap, nonspecific binding, available conjugation
      chemistries, and cellular toxicity. A complementary or alternative, label-free
      approach to molecular information is through multiplex coherent anti-Stokes Raman
      scattering (MCARS), which is a coherent, nonlinear optical method that provides a
      wealth of molecular information by probing the Raman energies within a molecule.
      In this work, we demonstrate the unique capability of our MCARS flow cytometer to
      distinguish flowing particles and discuss system performance capabilities and
      possibilities.

PMID- 20052215
TI  - Subwavelength hybrid terahertz waveguides.
AB  - We introduce and present general properties of hybrid terahertz waveguides.
      Weakly confined Zenneck waves on a metal-dielectric interface at terahertz
      frequencies can be transformed to a strongly confined yet low-loss subwavelength
      mode through coupling with a photonic mode of a nearby high-index dielectric
      strip. We analyze confinement, attenuation, and dispersion properties of this
      mode. The proposed design is suitable for planar integration and allows easy
      fabrication on chip scale. The superior waveguiding properties at terahertz
      frequencies could enable the hybrid terahertz waveguides as building blocks for
      terahertz integrated circuits.

PMID- 20052216
TI  - Single atom Rydberg excitation in a small dipole trap.
AB  - We have realized a single atom trap using a magneto-optical trap (MOT) with a
      high magnetic field gradient and a small optical dipole trap. Using this trap, we
      demonstrate the excitation to a highly excited Rydberg state (n=43) with a single
      Rubidium atom.

PMID- 20052217
TI  - Optical measurements of the laser-inducedultrasonic waves on moving objects.
AB  - We performed a single-shot, contactless measurement of ultrasonic waves on a
      laser-propelled rod with a homodyne quadrature laser interferometer (HQLI) during
      the entire duration of its motion. This is the first such experimental
      demonstration of the laser-induced motion of an elastic body where the most
      important mechanisms that reveal the nature of its motion are presented and
      explained. Furthermore, these measurements quantitatively demonstrate that the
      HQLI is an appropriate tool for monitoring high-amplitude (1.3 microm) and high
      frequency (200 MHz) ultrasonic waves on moving objects. The applicability of the
      HQLI can also be extended to measure other optodynamic and high-frequency
      transient phenomena with a constant sensitivity and a resolution below 1 nm.

PMID- 20052218
TI  - UV light emission from GZO/ZnO/GaN heterojunction diodes with carrier confinement
      layers.
AB  - In this work, GZO/ZnO/GaN diodes with the light emitting ZnO layer sandwiched
      between two SiO(2) thin films was fabricated and characterized. We observed a
      strong excitonic emission at the wavelength 377nm with the Mg(2+) deep level
      transition and oxygen vacancy induced recombination significantly suppressed. In
      comparison, light emission from the GZO/GaN device (without SiO(2) barriers) is
      mainly dominant by defect radiation. Furthermore, the device with confinement
      layers demonstrated a much higher UV intensity than the blue-green emission of
      the GZO/GaN p-n device.

PMID- 20052219
TI  - On-chip, planar integration of Er doped silicon-rich silicon nitride microdisk
      with SU-8 waveguide with sub-micron gap control.
AB  - On-chip, planar integration of Er-doped Silicon-rich silicon nitride microdisks
      with SU-8 waveguide and polymer cladding is achieved. The lack of high
      temperature or etching processes allows back-end integration without any optical
      damage to the microcavity resonator. The maximum measured Q-factor at 1475.5 nm
      was 13,000, corresponding to calculated intrinsic resonator Q-factor of 25,000
      that is limited by process-related roughness.

PMID- 20052220
TI  - Optical time-of-flight measurement based on data transmission in a ring
      oscillator.
AB  - We introduce a novel optical propagation delay measurement scheme for distance
      estimation. It is based on a ring oscillator in which the oscillation signal is
      replaced by the clock information contained in optical data. A clock-and-data
      recovery can recover the oscillation signal at the receive end. Correlation of
      the received pattern with the transmitted pattern and a measurement of the bit
      duration by a frequency counter allow to determine the distance. The scheme has
      been realized at 1550 nm wavelength, using an externally modulated laser, a
      commercial 155.52 Mb/s clock-and-data recovery and a field-programmable gate
      array. Short-term repeatability is <10 microm at an equivalent free-space
      distance of 72 m. Measurement interval is 0.1 s. At 3 km distance the relative
      repeatability is 8.10(-8). The readout can be corrected with measured temperature
      data.

PMID- 20052221
TI  - Laser selective cutting of biological tissues by impulsive heat deposition
      through ultrafast vibrational excitations.
AB  - Mechanical and thermodynamic responses of biomaterials after impulsive heat
      deposition through vibrational excitations (IHDVE) are investigated and
      discussed. Specifically, we demonstrate highly efficient ablation of healthy
      tooth enamel using 55 ps infrared laser pulses tuned to the vibrational
      transition of interstitial water and hydroxyapatite around 2.95 microm. The peak
      intensity at 13 GW/cm(2) was well below the plasma generation threshold and the
      applied fluence 0.75 J/cm(2) was significantly smaller than the typical ablation
      thresholds observed with nanosecond and microsecond pulses from Er:YAG lasers
      operating at the same wavelength. The ablation was performed without adding any
      superficial water layer at the enamel surface. The total energy deposited per
      ablated volume was several times smaller than previously reported for non
      resonant ultrafast plasma driven ablation with similar pulse durations. No micro
      cracking of the ablated surface was observed with a scanning electron microscope.
      The highly efficient ablation is attributed to an enhanced photomechanical effect
      due to ultrafast vibrational relaxation into heat and the scattering of powerful
      ultrafast acoustic transients with random phases off the mesoscopic heterogeneous
      tissue structures.

PMID- 20052222
TI  - Multiple-channel optical signal processing with wavelength-waveform conversions,
      pulsewidth tunability, and signal regeneration.
AB  - A multiple-channel multiple-function optical signal processor (MCMF-OSP)
      including wavelength-waveform conversions, pulsewidth tunability, and signal
      regeneration is realized through AND logic gate based on optical parametric
      processing with a pulsewidth-tunable RZ clock pump. The proposed scheme
      simultaneously offers four signal processing functions which are useful in
      wavelength-division multiplexing (WDM) transmission systems, and at network nodes
      with the necessity for multiple-channel data processing. After the discussions on
      the concept of MCMF-OSP, a proof-of concept experiment is demonstrated on four 10
      Gb/s nonreturn-to-zero (NRZ) data format channels using nonlinearities in
      semiconductor optical amplifier (SOA) and highly nonlinear fiber (HNLF). A
      wavelength and waveform conversions to return-to-zero (RZ) modulation format are
      obtained together with pulsewidth-tunable range from 20% to 80% duty cycles for
      all input signals. The converted signals inherit the timing and waveform of the
      RZ clock pump, thus resulting in a time regeneration and large tolerance to
      narrow-band optical filtering (NAOF) and fiber accumulated chromatic dispersion
      (CD).

PMID- 20052223
TI  - Spectral beam combination of fiber amplified ns-pulses by means of interference
      filters.
AB  - In this paper we introduce a simple scheme to spectrally combine four single
      beams using three low-cost dielectric interference filters as combining elements.
      25 ns pulses from four independent and actively Q-switched fiber seed-sources are
      amplified in a single stage fiber-amplifier. Temporally and spatially combined
      208 W of average power and 6.3 mJ of pulse energy are obtained at two different
      repetition frequencies. A detailed analysis of beam quality as well as the
      thermal behavior of the combining elements is carried out and reveals mutual
      dependency.

PMID- 20052224
TI  - Instantaneous frequency measurement system using optical mixing in highly
      nonlinear fiber.
AB  - A broadband photonic instantaneous frequency measurement system utilizing four
      wave mixing in highly nonlinear fiber is demonstrated. This new approach is
      highly stable and does not require any high-speed electronics or photodetectors.
      A first principles model accurately predicts the system response. Frequency
      measurement responses from 1 to 40 GHz are demonstrated and simple
      reconfiguration allows the system to operate over multiple bands.

PMID- 20052225
TI  - Non-mechanical sub-pixel image shifter for acquiring super-resolution digital
      images.
AB  - A sub-pixel image shifter is presented, for use in enhancing the spatial
      resolution of digital image sensors by combining multiple displaced sub-images
      using a super-resolution (SR) algorithm. The device uses the walk-off phenomenon
      in birefringent crystals to separate images with opposite polarizations by a sub
      pixel displacement. A liquid crystal (LC) waveplate plus a polarizer can then
      select the specific image to be exposed, with fast, non-mechanical control. This
      cascaded device, comprising two sapphire crystals, two LCs, and a single
      polarizer, is capable of 2-dimensional image shift with displacements of 0.5
      pixels. The experimental results show that the image registration stability can
      be precisely controlled within 0.05 pixels and the contrast transfer function
      ratio of the SR image is enhanced by up to 1.36 times compared to the original
      captured image. Moreover, based on the fast transition time of LCs, the displaced
      sub-images can be recorded in video form with a frame rate of 40 fps.

PMID- 20052226
TI  - Magneto-optical trapping and background-free imaging for atoms near
      nanostructured surfaces.
AB  - We demonstrate a combined magneto-optical trap and imaging system that is
      suitable for the investigation of cold atoms near surfaces. In particular, we are
      able to trap atoms close to optically scattering surfaces and to image them with
      an excellent signal-to-noise ratio. We also demonstrate a simple magneto-optical
      atom cloud launching method. We anticipate that this system will be useful for a
      range of experimental studies of novel atom-surface interactions and atom trap
      miniaturization. .

PMID- 20052227
TI  - Investigation of mode coupling in a microdisk resonator for realizing directional
      emission.
AB  - Mode coupling between the whispering-gallery modes (WGMs) is numerically
      investigated for a two-dimensional microdisk resonator with an output waveguide.
      The equilateral-polygonal shaped mode patterns can be constructed by mode
      coupling in the microdisk, and the coupled modes can still keep high quality
      factors (Q factors). For a microdisk with a diameter of 4.5 microm and a
      refractive index of 3.2 connected to a 0.6-microm-wide output waveguide, the
      coupled mode at the wavelength of 1490 nm has a Q factor in the order of 10(4),
      which is ten times larger than those of the uncoupled WGMs, and the output
      efficiency defined as the ratio of the energy flux confined in the output
      waveguide to the total radiation energy flux is about 0.65. The mode coupling can
      be used to realize high efficiency directional-emission microdisk lasers.

PMID- 20052228
TI  - High-visibility interference fringes with femtosecond laser radiation.
AB  - We propose and experimentally demonstrate an interferometer for femtosecond
      pulses with spectral bandwidth about 100 nm. The scheme is based on a Michelson
      interferometer with a dispersion compensating module. A diffractive lens serves
      the purpose of equalizing the optical-path-length difference for a wide range of
      frequencies. In this way, it is possible to register high-contrast interference
      fringes with micrometric resolution over the whole area of a commercial CCD
      sensor for broadband femtosecond pulses.

PMID- 20052229
TI  - Photo-thermal measurement of absorptance losses, temperature induced wavefront
      deformation and compaction in DUV-optics.
AB  - A measurement system for quantitative registration of transient and irreversible
      lens effects in DUV optics induced by absorbed UV laser radiation was developed.
      It is based upon a strongly improved Hartmann-Shack wavefront sensor with an
      extreme sensitivity of approximately lambda/10000 rms @ 193nm, accomplishing
      precise on-line monitoring of wavefront deformations of a collimated test laser
      beam transmitted through the laser-irradiated site of a sample. Caused by the
      temperature dependence of the refractive index as well as thermal expansion, the
      initially plane wavefront of the test laser is distorted into a convex or concave
      lens, depending on sign and magnitude of index change and expansion. This
      transient wavefront distortion yields a quantitative measure of the absorption
      losses in the sample. In the case of fused silica, an additional permanent change
      indicates irreversible material compaction. Results for both fused silica and
      CaF(2) are presented and compared.

PMID- 20052230
TI  - Optoacoustic induced vibrations within the inner ear.
AB  - An acoustic transient can be generated inside an absorbing tissue as a result of
      laser-tissue interaction after pulsed laser irradiation. Herein we report a novel
      application of this physical process, the optoacoustic wave generation in the
      inner ear and subsequently the induction of basilar membrane vibrations. These
      laser induced vibrations show a direct correlation to the laser energy and an
      indirect correlation to the distance from the irradiation focus. Through these
      characteristics they may be used, in a new generation of cochlear implants, to
      improve the frequency specific cochlear activation and consequently improve
      speech perception in hearing impaired patients with residual hearing.

PMID- 20052231
TI  - Optimum input states of polarization for Mueller matrix measurement in a system
      having finite polarization-dependent loss or gain.
AB  - We present the theoretical and simulation results of the relationship between
      three input states of polarization (SOP) and the Mueller matrix measurement error
      in an optical system having birefringence and finite polarization-dependent loss
      or gain (PDL/G). By using the condition number as the criterion, it can be
      theoretically demonstrated that the three input SOPs should be equally-spaced on
      the Poincare sphere and centered on the reversed PDL/G vector to achieve better
      measurement accuracy in a single test. Further, an upper bound of the mean of the
      Mueller matrix measurement error is derived when the measurement errors of output
      Stokes parameters independently and identically follow the ideal Gaussian
      distribution. This upper bound also shows that the statistically best Mueller
      matrix measurement accuracy can be obtained when the three input SOPs have the
      same relationship mentioned above. Simulation results confirm the validity of the
      theoretical findings.

PMID- 20052232
TI  - Light trapping in thin-film silicon solar cells with submicron surface texture.
AB  - The influence of nano textured front contacts on the optical wave propagation
      within microcrystalline thin-film silicon solar cell was investigated. Periodic
      triangular gratings were integrated in solar cells and the influence of the
      profile dimensions on the quantum efficiency and the short circuit current was
      studied. A Finite Difference Time Domain approach was used to rigorously solve
      the Maxwell's equations in two dimensions. By studying the influence of the
      period and height of the triangular profile, the design of the structures were
      optimized to achieve higher short circuit currents and quantum efficiencies.
      Enhancement of the short circuit current in the blue part of the spectrum is
      achieved for small triangular periods (P<200 nm), whereas the short circuit
      current in the red and infrared part of the spectrum is increased for triangular
      periods (P = 900nm) comparable to the optical wavelength. The influence of the
      surface texture on the solar cell performance will be discussed.

PMID- 20052233
TI  - Shaped focal plane detectors for particle concentration and mean size
      observations.
AB  - We describe a method of designing shaped focal plane detectors for achieving a
      range of objectives in measurement of particles suspended in a fluid. These
      detectors can be designed to measure the total concentration in a wide size range
      (e.g. 200:1) or concentration in a size sub-range (e.g. 63<d<500 microm), and
      Sauter mean or volume mean diameter. The derivation of these shaped focal plane
      detectors is rooted in small-angle forward light scattering. The detector shapes
      are completely general, requiring no assumptions on underlying particle size
      distribution. We show the theoretical development, numerical simulations and
      laboratory test results.

PMID- 20052234
TI  - Linear and nonlinear discrete light propagation in weakly modulated large-area
      two-dimensional photonic lattice slab in LiNbO3:Fe crystal.
AB  - A weakly modulated large-area two-dimensional square photonic lattice slab was
      fabricated through optical induction technique in a photorefractive photovoltaic
      LiNbO(3):Fe crystal. Bragg-matched diffraction technique was used to characterize
      the square photonic lattice slab. Interestingly, linear discrete diffraction
      typical for waveguide arrays was observed in such a square photonic lattice slab,
      indicating that the lattice slab can be viewed effectively as a one-dimensional
      waveguide array. Furthermore, discrete soliton was demonstrated in the photonic
      lattice slab due to a saturable self-defocusing nonlinearity arising from the
      bulk photorefractive photovoltaic effect of LiNbO(3):Fe.

PMID- 20052235
TI  - Measuring directionality of the retinal reflection with a Shack-Hartmann
      wavefront sensor.
AB  - The directional sensitivity of the retina, known as the Stiles-Crawford effect
      (SCE), originates from the waveguide property of photoreceptors. This effect has
      been extensively studied in normal and pathologic eyes using highly customized
      optical instrumentation. Here we investigate a new approach based on a Shack
      Hartmann wavefront sensor (SHWS), a technology that has been traditionally
      employed for measuring wave aberrations (phase) of the eye and is available in
      clinics. Using a modified research-grade SHWS, we demonstrate in five healthy
      subjects and at four retinal eccentricities that intensity information can be
      readily extracted from the SHWS measurement and the spatial distribution of which
      is consistent with that produced by the optical SCE. The technique is found
      sufficiently sensitive even at near-infrared wavelengths where the optical SCE is
      faint. We demonstrate that the optical SCE signal is confined to the core of the
      SHWS spots with the tails being diffuse and non-directional, suggesting cones
      fail to recapture light that is multiply scattered in the retina. The high
      sensitivity of the SHWS to the optical SCE raises concern as to how this effect,
      intrinsic to the retina, may impact the SHWS measurement of ocular aberrations.

PMID- 20052236
TI  - Compact picosecond mode-locked and cavity-dumped Nd:YVO4 laser.
AB  - We report on a diode pumped, semiconductor saturable absorber mirror mode-locked
      picosecond Nd:YVO(4) oscillator with cavity-dumping. In pure cw-mode-locking this
      laser produced up to 17W of average power at a pulse repetition rate of 9.7MHz,
      corresponding to a pulse energy of 1.7microJ. Using an electro-optic cavity
      dumper, we achieved average powers up to 7.8W at 500kHz and 10W at 1MHz dumping
      rate. With corresponding pulse energies of 15.6microJ and 10microJ respectively
      and pulsewidths around 10ps, this laser could become a compact source for
      materials processing applications, alternative to more complex schemes such as
      regenerative amplifiers or ultra-long resonator oscillators.

PMID- 20052237
TI  - Intensity sensitivity of gold nanostructures and its application for high
      throughput biosensing.
AB  - A new microarray for dynamical studies of surface biomolecular interactions
      without fluorescent labeling is proposed. We employed gold nanostructures to
      excite surface plasmons on the microarray surface and detected the intensity
      changes in the extraordinary transmission. The calculation and measurement
      results indicate that the nanoslit array has an intensity sensitivity much higher
      than the nanohole array due to its narrower resonant bandwidth. In addition, the
      sensitivity is increased as the slit width decreases. For 35 nm slit width, the
      intensity sensitivity reaches to approximately 4000%/RIU, two times larger than
      the slit width larger than 150 nm. Using the intensity changes, we demonstrate a
      10 x 10 microarray for real-time measurements of antigen-antibody and DNA-DNA
      interactions.

PMID- 20052238
TI  - Magnetomotive nanoparticle transducers for optical rheology of viscoelastic
      materials.
AB  - The availability of a real-time non-destructive modality to interrogate the
      mechanical properties of viscoelastic materials would facilitate many new
      investigations. We introduce a new optical method for measuring elastic
      properties of samples which employs magnetite nanoparticles as perturbative
      agents. Magnetic nanoparticles distributed in silicone-based samples are
      displaced upon probing with a small external magnetic field gradient and depth
      resolved optical coherence phase shifts allow for the tracking of scatterers in
      the sample with nanometer-scale sensitivity. The scatterers undergo underdamped
      oscillations when the magnetic field is applied step-wise, allowing for the
      measurement of the natural frequencies of oscillation of the samples. Validation
      of the measurements is accomplished using a commercial indentation apparatus to
      determine the elastic moduli of the samples. This real-time non-destructive
      technique constitutes a novel way of probing the natural frequencies of
      viscoelastic materials in which magnetic nanoparticles can be introduced.

PMID- 20052239
TI  - Tunable multi-wavelength fiber lasers based on an Opto-VLSI processor and optical
      amplifiers.
AB  - A multi-wavelength tunable fiber laser based on the use of an Opto-VLSI processor
      in conjunction with different optical amplifiers is proposed and experimentally
      demonstrated. The Opto-VLSI processor can simultaneously select any part of the
      gain spectrum from each optical amplifier into its associated fiber ring, leading
      to a multiport tunable fiber laser source. We experimentally demonstrate a 3-port
      tunable fiber laser source, where each output wavelength of each port can
      independently be tuned within the C-band with a wavelength step of about 0.05 nm.
      Experimental results demonstrate a laser linewidth as narrow as 0.05 nm and an
      optical side-mode-suppression-ratio (SMSR) of about 35 dB. The demonstrated three
      fiber lasers have excellent stability at room temperature and output power
      uniformity less than 0.5 dB over the whole C-band.

PMID- 20052240
TI  - Stabilization and breakup of optical vortices in presence of hybrid nonlinearity.
AB  - We study nonlinear propagation of optical vortices in presence of hybrid
      nonlinearity as established in a nonconventional biased photorefractive crystal.
      Our results indicate that under hybrid nonlinearity the breakup of a singly
      charged vortex along with the loss of its angular momentum is suppressed
      considerably as compared with that under conventional self-focusing or self
      defocusing nonlinearity. Disintegration of a doubly-charged vortex under hybrid
      nonlinearity is also presented. Our experimental results are in good agreement
      with the numerical simulations.

PMID- 20052241
TI  - Transition dynamics for multi-pulsing in mode-locked lasers.
AB  - We consider experimentally and theoretically a refined parameter space in a laser
      system near the transition to multi-pulse modelocking. Near the transition, the
      onset of instability is initiated by a Hopf (periodic) bifurcation. As the cavity
      energy is increased, the band of unstable, oscillatory modes generates a chaotic
      behavior between single- and multi-pulse operation. Both theory and experiment
      are in good qualitative agreement and they suggest that the phenomenon is of a
      universal nature in mode-locked lasers at the onset of multi-pulsing from N to N
      +1 pulses per round trip. This is the first theoretical and experimental
      characterization of the transition behavior, made possible by a highly refined
      tuning of the gain pump level.

PMID- 20052242
TI  - Real-time 2D parallel windowed Fourier transform for fringe pattern analysis
      using Graphics Processing Unit.
AB  - In optical interferometers, fringe projection systems, and synthetic aperture
      radars, fringe patterns are common outcomes and usually degraded by unavoidable
      noises. The presence of noises makes the phase extraction and phase unwrapping
      challenging. Windowed Fourier transform (WFT) based algorithms have been proven
      to be effective for fringe pattern analysis to various applications. However, the
      WFT-based algorithms are computationally expensive, prohibiting them from real
      time applications. In this paper, we propose a fast parallel WFT-based library
      using graphics processing units and computer unified device architecture. Real
      time WFT-based algorithms are achieved with 4 frames per second in processing
      256x256 fringe patterns. Up to 132x speedup is obtained for WFT-based algorithms
      using NVIDIA GTX295 graphics card than sequential C in quad-core 2.5GHz
      Intel(R)Xeon(R) CPU E5420.

PMID- 20052243
TI  - Three-color Sagnac source of polarization-entangled photon pairs.
AB  - We demonstrate a compact and stable source of polarization-entangled pairs of
      photons, one at 810 nm wavelength for high detection efficiency and the other at
      1550 nm for long-distance fiber communication networks. Due to a novel Sagnac
      based design of the interferometer no active stabilization is needed. Using only
      one 30 mm ppKTP bulk crystal the source produces photons with a spectral
      brightness of 1.13 x 10(6) pairs/s/mW/THz with an entanglement fidelity of 98.2%.
      Both photons are single-mode fiber coupled and ready to be used in quantum key
      distribution (QKD) or transmission of photonic quantum states over large
      distances.

PMID- 20052244
TI  - Quantum dot infrared photodetector enhanced by surface plasma wave excitation.
AB  - Up to a thirty-fold detectivity enhancement is achieved for an InAs quantum dot
      infrared photodetector (QDIP) by the excitation of surface plasma waves (SPWs)
      using a metal photonic crystal (MPC) integrated on top of the detector absorption
      region. The MPC is a 100 nm-thick gold film perforated with a 3.6 microm period
      square array of circular holes. A bare QDIP shows a bias-tunable broadband
      response from approximately 6 to 10 microm associated with the quantum confined
      Stark (QCS) effect. On the other hand, an MPC-integrated QDIP exhibits a dominant
      peak at 11.3 microm with a approximately 1 microm full width at half maximum and
      the highly enhanced detectivity at the bias polarity optimized for long
      wavelength. This is very different from the photoresponse of the bare QDIP but
      fully consistent with the direct coupling of the QDs in the detector absorption
      region to the SPWs excited at the MPC/detector interface by incident photons. The
      SPW resonance wavelength, lambda, for the smallest coupling wavevector of the
      array in the MPC is close to 11.3 microm. The response also shows other SPW
      coupled peaks: a significant peak at 8.1 microm (approximately lambda/radical2)
      and noticeable peaks at 5.8 microm (approximately lambda/2) and 5.4 microm
      (approximately lambda/ radical5) which correspond to higher-order coupling
      wavevectors. For the opposite bias, the MPC-integrated QDIP shows the highest
      response at 8.1 microm, providing a dramatic voltage tunability that is
      associated with QCS effect. SPWs propagate with TM (x, z) polarization along the
      MPC/detector interface. The enhanced detectivity is explained by these
      characteristics which increase both the effective absorption cross section with
      propagation and the interaction strength with TM polarization in the coupling to
      the QDs. Simulations show good qualitative agreement with the observed spectral
      behavior.

PMID- 20052245
TI  - Numerical comparison between conventional dispersion compensating fibers and
      photonic crystal fibers as lumped Raman amplifiers.
AB  - In this paper we discuss the use of photonic crystal fibers (PCFs) as discrete
      devices for simultaneous wideband dispersion compensation and Raman
      amplification. The performance of the PCFs in terms of gain, ripple, optical
      signal-to-noise ratio (OSNR) and required fiber length for complete dispersion
      compensation is compared with conventional dispersion compensating fibers (DCFs).
      The main goal is to determine the minimum PCF loss beyond which its performance
      surpasses a state-of-the-art DCF and justifies practical use in telecommunication
      systems.

PMID- 20052246
TI  - phi2FLIM: a technique for alias-free frequency domain fluorescence lifetime
      imaging.
AB  - A new approach to alias-free wide-field fluorescence lifetime imaging in the
      frequency domain is demonstrated using a supercontinuum source for fluorescence
      excitation and a phase-modulated image intensifier for detection. This technique
      is referred to as phi-squared fluorescence lifetime imaging (phi(2)FLIM). The
      phase modulation and square-wave gating of the image intensifier eliminate
      aliasing by the effective suppression of higher harmonics. The ability to use
      picosecond excitation pulses without aliasing expands the range of excitation
      sources available for frequency-domain fluorescence lifetime imaging (fd-FLIM)
      and improves the modulation depth of conventional homodyne fd-FLIM measurements,
      which use sinusoidal intensity modulation of the excitation source. The
      phi(2)FLIM results are analyzed using AB-plots, which facilitate the
      identification of mono-exponential and multi-exponential fluorescence decays and
      provide measurements of the fluorophore fractions in two component mixtures. The
      rapid acquisition speed of the technique enables lifetime measurements in dynamic
      systems, such as temporally evolving samples and samples that are sensitive to
      photo-bleaching. Rapid phi(2)FLIM measurements are demonstrated by imaging the
      dynamic mixing of two different dye solutions at 5.5 Hz. The tunability of
      supercontinuum radiation enables excitation wavelength resolved FLIM
      measurements, which facilitates analysis of samples containing multiple
      fluorophores with different absorption spectra.

PMID- 20052247
TI  - Nonlinear trimer resonators for compact ultra-fast switching.
AB  - We propose and numerically verify a scheme for compact optical modulation which
      can enable complex directional switching of signals in integrated micro-optical
      circuits within hundreds of femtoseconds. The scheme is based on a trimer
      comprised of two identical silica whispering gallery mode (WGM) microresonators
      spaced by a central non-linear WGM resonator. The non-linear resonator is in the
      form of a silica cylinder with a thin coating of an ultrafast Kerr nonlinear
      material (a J-aggregate of cyanine dye). Using a two-dimensional finite
      difference time-domain method and realistic material and structural parameters,
      we investigated the near-field coupling from a waveguide to the trimer and the
      subsequent switching process. In our scheme the sandwiched central control
      resonator has a resonant frequency that is mismatched to that of the input and
      output resonators. Therefore the optical energy is coupled from the waveguide
      into only the primary resonator in linear operation. However, for control light
      intensities of more than approximately 10(-2) W/microm the effective index and
      hence eigenfrequency of the central resonator can be shifted to match that of its
      neighbors and hence the optical energy can be redirected.

PMID- 20052248
TI  - Support-assisted optical superresolution of low-resolution image sequences: the
      one-dimensional problem.
AB  - We analyze the problem of optical superresolution (OSR) of a one-dimensional (1D)
      incoherent spatial signal from undersampled data when the support of the signal
      is known in advance. The present paper corrects and extends our previous work on
      the calculation of Fisher information (FI) and the associated Cramer-Rao lower
      bound (CRB) on the minimum error for estimating the signal intensity distribution
      and its Fourier components at spatial frequencies lying beyond the optical band
      edge. The faint-signal and bright-signal limits emerge from a unified noise
      analysis in which we include both additive noise of detection and shot noise of
      photon counting via an approximate Gaussian statistical distribution. For a large
      space-bandwidth product, we derive analytical approximations to the exact
      expressions for FI and CRB in the faint-signal limit and use them to argue why
      achieving any significant amount o unbiased bandwidth extension in the presence
      of noise is a uniquely challenging proposition. Unlike previous theoretical work
      on the subject of support-assisted bandwidth extension, our approach is not
      restricted to specific forms of the system transfer functions, and provides a
      unified analysis of both digital and optical superresolution of undersampled
      data.

PMID- 20052249
TI  - Radial polarization interferometer.
AB  - We propose and demonstrate a new interferometric approach in which a uniform
      phase difference between the arms of the interferometer manifests itself as
      spatially varying intensity distribution. The approach is based on interfering
      two orthogonal spatially varying vector fields, the radially and azimuthally
      polarized beams, and measuring the projection of the obtained field on an
      analyzer. This method provides additional spatial information that can be used to
      improve the smallest detectable phase change as compared with a conventional
      Michelson interferometer.

PMID- 20052250
TI  - Integration of GaN/AlN all-optical switch with SiN/AlN waveguide utilizing spot
      size conversion.
AB  - Spot-size converters for an all-optical switch utilizing the intersubband
      transition in GaN/AlN multiple quantum wells are studied with the purpose of
      reducing operation power by improving the coupling efficiency between the input
      fiber and the switch. With a stair-like spot-size converter, the absorption
      saturation of 5 dB is achieved with a pulse energy of 25 pJ. The switch is
      integrated with a SiN/AlN waveguide and spot-size converters, and the structure
      provides the possibility of an integration of the switch with other functional
      devices. To further improve the coupling loss between the waveguide and the
      switch, triangular-shaped converters are investigated, demonstrating losses as
      low as 2 dB/facet.

PMID- 20052251
TI  - Theoretical analysis of a fiber optic surface plasmon resonance sensor utilizing
      a Bragg grating.
AB  - A rigorous theoretical analysis of a fiber optic surface plasmon resonance sensor
      is presented. The sensor is based on the spectroscopy of mixed surface plasmon-
      fiber cladding modes excited by the fundamental mode of an optical fiber via a
      Bragg grating formed in the fiber core. The transmission spectrum is calculated
      by means of the Coupled Mode Theory. The modal structure is theoretically
      analyzed using a 3-D method based on a field expansion approach for matching the
      field continuity at the boundary of the layers. The theoretical analysis revealed
      a series of narrow transmission dips associated with the coupling of the
      fundamental mode to the mixed surface plasmon--fiber cladding modes. The
      sensitivity of these dips to changes in the refractive index of the analyte is
      calculated. Moreover, the refractive index resolution of the sensor was estimated
      to be better than 2 x 10(-6) RIU.

PMID- 20052252
TI  - Ultra-low-threshold Er:Yb sol-gel microlaser on silicon.
AB  - Ultra-low threshold lasers which operate in the telecommunications band and which
      can be integrated with other CMOS compatible elements have numerous applications
      in satellite communications, biochemical detection and optical computing. To
      achieve sub-mW lasing thresholds, it is necessary to optimize both the gain
      medium and the pump method. One of the most promising methods is to use rare
      earth ions in a co- or tri-dopant configuration, where the lasing of the primary
      dopant is enhanced by the secondary one, thus improving the efficiency of the
      overall system. Here, we demonstrate an Erbium:Ytterbium co-doped microcavity
      based laser which is lithographically fabricated on a silicon substrate. The
      quality factor and pump threshold are experimentally determined for a series of
      erbium and ytterbium doping concentrations, verifying the inter-dependent
      relationship between the two dopants. The lasing threshold of the optimized
      device is 4.2 microW.

PMID- 20052253
TI  - Automatic exposure control and estimation of effective system noise in diffuse
      fluorescence tomography.
AB  - A diffuse fluorescence tomography system, based upon time-correlated single
      photon counting, is presented with an automated algorithm to allow dynamic range
      variation through exposure control. This automated exposure control allows the
      upper and lower detection levels of fluorophore to be extended by an order of
      magnitude beyond the previously published performance and benefits in a slight
      decrease in system effective noise. The effective noise level is used as a metric
      to characterize the system performance, integrating both model-mismatch and
      calibration bias errors into a single parameter. This effective error is near 7%
      of the reconstructed fluorescent yield value, when imaging in just few minutes.
      Quantifying protoporphyrin IX concentrations down to 50 ng/ml is possible, for
      tumor-sized regions. This fluorophore has very low fluorescence yield, but high
      biological relevance for tumor imaging, given that it is produced in the
      mitochondria, and upregulated in many tumor types.

PMID- 20052254
TI  - Directionally controlled 3D ferroelectric single crystal growth in LaBGeO5 glass
      by femtosecond laser irradiation.
AB  - Laser-fabrication of complex, highly oriented three-dimensional ferroelectric
      single crystal architecture with straight lines and bends is demonstrated in
      lanthanum borogermanate model glass using a high repetition rate femtosecond
      laser. Scanning micro-Raman microscopy shows that the c-axis of the ferroelectric
      crystal is aligned with the writing direction even after bending. A gradual
      rather than an abrupt transition is observed for the changing lattice orientation
      through bends up to approximately 14 degrees. Thus the single crystal character
      of the line is preserved along the bend through lattice straining rather than
      formation of a grain boundary.

PMID- 20052255
TI  - A single W/B4C transmission multilayer for polarization analysis of soft x-rays
      up to 1keV.
AB  - A transmission W/B(4)C multilayer has been designed and characterized which shows
      significant phase retardation up to a photon energy of 1 keV, when operated near
      the Bragg condition. This allows, for the first time, the full polarization
      vector of soft x-radiation to be measured up to 1 keV in a self-calibrating
      method. Quantitative polarimetry is now possible across the 2p edges of all the
      transition metals.

PMID- 20052256
TI  - A passive method to compensate nonlinearity in a homodyne interferometer.
AB  - This study presents an analysis of the nonlinearity resulting from polarization
      crosstalk at a polarizing beam splitter (PBS) and a wave plate (WP) in a homodyne
      interferometer. From a theoretical approach, a new compensation method involving
      a realignment of the axes of WPs to some specific angles according to the
      characteristics of the PBS is introduced. This method suppresses the nonlinearity
      in a homodyne interferometer to 0.36 nm, which would be 3.75 nm with conventional
      alignment methods of WPs.

PMID- 20052257
TI  - Non-resonant wavelength modulation saturation spectroscopy in acetylene-filled
      hollow-core photonic bandgap fibres applied to modulation-free laser diode
      stabilisation.
AB  - In this paper the application of Wavelength Modulation (WM) techniques to non
      resonant saturation spectroscopy in acetylene-filled Hollow-Core Photonic Bandgap
      Fibres (HC-PBFs) and modulation-free Laser Diode (LD) frequency stabilisation is
      investigated. In the first part WM techniques are applied to non-resonant pump
      probe saturation of acetylene overtone rotational transitions in a HC-PBF. A high
      power DFB chip-on-carrier mounted LD is used in conjunction with a tuneable
      External Cavity Laser (ECL) and the main saturation parameters are characterized.
      In the second part a novel feedback system to stabilize the DFB emission
      wavelength based on the WM saturation results is implemented. Modulation-free
      locking of the DFB laser frequency to the narrow linewidth saturation feature is
      achieved for both constant and variable LD temperatures.

PMID- 20052258
TI  - Direct observation of the transfer of orbital angular momentum to metal particles
      from a focused circularly polarized Gaussian beam.
AB  - It is well known that a circularly polarized Gaussian beam carries spin angular
      momentum, but not orbital angular momentum. This paper demonstrates that focusing
      a beam carrying spin angular momentum can induce an orbital angular momentum
      which we used to drive the orbital motion of a micron-sized metal particle that
      is trapped off the beam axis. The direction of the orbital motion is controlled
      by the handedness of the circular polarization. The orbiting dynamics of the
      trapped particle, which acted as an optical micro-detector, were quantitatively
      measured and found to be in excellent agreement with the theoretical predictions.

PMID- 20052259
TI  - Subwavelength silicon microcavities.
AB  - We present a study of the first silicon microdisk resonators which are smaller
      than the free-space resonant wavelength in all spatial dimensions. Spectral
      details of whispering gallery modes with azimuthal mode number m = 4-7 are
      measured in microdisks with diameters between 1.35 and 1.89microm and are studied
      at wavelengths from 1.52 to 1.62microm. For the structures considered here, m = 5
      is the highest azimuthal mode order in a subwavelength cavity and has measured Q
      = 1250. These results agree well with theoretical calculations using a finite
      difference frequency domain method and fit an exponential scaling law relating Q
      to disk radius via m.

PMID- 20052260
TI  - Dual-channel all-optical wavelength conversion switching by four-wave mixing.
AB  - We report an experimental demonstration of dual-channel all-optical wavelength
      conversion switching in hot Rb vapor. In a four-level atomic system, a coupling
      field and a pump field interact with both (87)Rb and (85)Rb isotopes
      simultaneously and facilitate the generation of two nonlinear signals when the
      probe field is applied to the corresponding transition. Each nonlinear signal is
      switched on and off separately by the pump field at different frequencies based
      on four-wave mixing and isotope shifts.

PMID- 20052261
TI  - Digital reconstruction of optically-induced potentials.
AB  - The holographic reconstruction of optically-induced objects typically assumes
      that the object is axially thin. Here, we demonstrate a simple approach that
      works for axially thick objects which evolve dynamically. Results are verified by
      reconstructing linear scattering experiments in a self-defocusing photorefractive
      crystal.

PMID- 20052262
TI  - High-efficiency, high-power and low threshold Yb3+:YAG ceramic laser.
AB  - We present a high-power, high-efficiency and low threshold laser prototype based
      on doped ceramic Yb(3+):YAG. We achieved an output power of 9 W with a slope
      efficiency of 73% and a threshold of 1 W at 1030 nm in quasi-Continuous Wave
      (QCW). Moreover, we obtained an output power 7.7 W with a slope efficiency of 60%
      in Continuous Wave (CW). Finally, a characterization of a low losses tunable
      cavity for several laser wavelengths with an output power exceeding 5 W is
      reported.

PMID- 20052265
TI  - The horizon of unintentional injuries among children in low-income setting: an
      overview from Bangladesh Health and Injury Survey.
AB  - INTRODUCTION: The paper aims to explore the magnitude and distribution of
      unintentional injuries among Bangladeshi children (<18 years). METHODOLOGY: A
      cross sectional survey was conducted during 2003 (January to December) in 12
      randomly selected districts and Dhaka Metropolitan City of Bangladesh. Nationally
      representative data were collected from 171 366 households comprising of 351 651
      children of under 18 years. Information includes the number of deaths and illness
      at the household in the preceding year. Verbal autopsy and verbal diagnosis form
      was used to determine the cause of mortality and morbidity respectively. RESULTS:
      There were 351651 children in the study, of which 5577 had one or more injuries
      in the past one year. Drowning and falls was the leading cause of injury
      mortality and morbidity in children over 1 year of age respectively. Incidence of
      unintentional injuries was significantly higher among boys (95% CI = -2157.8)
      than girls (95% CI = 968.7 - 1085.8) while rural children were the most
      vulnerable group. Home and its premises was the most common place for the injury
      incidence. CONCLUSION: The result of the study could be an insight to the policy
      makers to develop realistic and effective strategies to address the issue.

PMID- 20052266
TI  - Identification of networks of co-occurring, tumor-related DNA copy number changes
      using a genome-wide scoring approach.
AB  - Tumorigenesis is a multi-step process in which normal cells transform into
      malignant tumors following the accumulation of genetic mutations that enable them
      to evade the growth control checkpoints that would normally suppress their growth
      or result in apoptosis. It is therefore important to identify those combinations
      of mutations that collaborate in cancer development and progression. DNA copy
      number alterations (CNAs) are one of the ways in which cancer genes are
      deregulated in tumor cells. We hypothesized that synergistic interactions between
      cancer genes might be identified by looking for regions of co-occurring gain
      and/or loss. To this end we developed a scoring framework to separate truly co
      occurring aberrations from passenger mutations and dominant single signals
      present in the data. The resulting regions of high co-occurrence can be
      investigated for between-region functional interactions. Analysis of high
      resolution DNA copy number data from a panel of 95 hematological tumor cell lines
      correctly identified co-occurring recombinations at the T-cell receptor and
      immunoglobulin loci in T- and B-cell malignancies, respectively, showing that we
      can recover truly co-occurring genomic alterations. In addition, our analysis
      revealed networks of co-occurring genomic losses and gains that are enriched for
      cancer genes. These networks are also highly enriched for functional
      relationships between genes. We further examine sub-networks of these networks,
      core networks, which contain many known cancer genes. The core network for co
      occurring DNA losses we find seems to be independent of the canonical cancer
      genes within the network. Our findings suggest that large-scale, low-intensity
      copy number alterations may be an important feature of cancer development or
      maintenance by affecting gene dosage of a large interconnected network of
      functionally related genes.

PMID- 20052267
TI  - Detection of Mycolactone A/B in Mycobacterium ulcerans-Infected Human Tissue.
AB  - BACKGROUND: Mycobacterium ulcerans disease (Buruli ulcer) is a neglected tropical
      disease common amongst children in rural West Africa. Animal experiments have
      shown that tissue destruction is caused by a toxin called mycolactone.
      METHODOLOGY/PRINCIPAL FINDINGS: A molecule was identified among acetone-soluble
      lipid extracts from M. ulcerans (Mu)-infected human lesions with chemical and
      biological properties of mycolactone A/B. On thin layer chromatography this
      molecule had a retention factor value of 0.23, MS analyses showed it had an m/z
      of 765.6 [M+Na(+)] and on MS:MS fragmented to produce the core lactone ring with
      m/z of 429.4 and the polyketide side chain of mycolactone A/B with m/z of 359.2.
      Acetone-soluble lipids from lesions demonstrated significant cytotoxic, pro
      apoptotic and anti-inflammatory activities on cultured fibroblast and macrophage
      cell lines. Mycolactone A/B was detected in all of 10 tissue samples from
      patients with ulcerative and pre-ulcerative Mu disease. CONCLUSIONS/SIGNIFICANCE:
      Mycolactone can be detected in human tissue infected with Mu. This could have
      important implications for successful management of Mu infection by antibiotic
      treatment but further studies are needed to measure its concentration.

PMID- 20052268
TI  - Syphilis at the crossroad of phylogenetics and paleopathology.
AB  - The origin of syphilis is still controversial. Different research avenues explore
      its fascinating history. Here we employed a new integrative approach, where
      paleopathology and molecular analyses are combined. As an exercise to test the
      validity of this approach we examined different hypotheses on the origin of
      syphilis and other human diseases caused by treponemes (treponematoses).
      Initially, we constructed a worldwide map containing all accessible reports on
      palaeopathological evidences of treponematoses before Columbus's return to
      Europe. Then, we selected the oldest ones to calibrate the time of the most
      recent common ancestor of Treponema pallidum subsp. pallidum, T. pallidum subsp.
      endemicum and T. pallidum subsp. pertenue in phylogenetic analyses with 21
      genetic regions of different T. pallidum strains previously reported. Finally, we
      estimated the treponemes' evolutionary rate to test three scenarios: A) if
      treponematoses accompanied human evolution since Homo erectus; B) if venereal
      syphilis arose very recently from less virulent strains caught in the New World
      about 500 years ago, and C) if it emerged in the Americas between 16,500 and
      5,000 years ago. Two of the resulting evolutionary rates were unlikely and do not
      explain the existent osseous evidence. Thus, treponematoses, as we know them
      today, did not emerge with H. erectus, nor did venereal syphilis appear only five
      centuries ago. However, considering 16,500 years before present (yBP) as the time
      of the first colonization of the Americas, and approximately 5,000 yBP as the
      oldest probable evidence of venereal syphilis in the world, we could not entirely
      reject hypothesis C. We confirm that syphilis seems to have emerged in this time
      span, since the resulting evolutionary rate is compatible with those observed in
      other bacteria. In contrast, if the claims of precolumbian venereal syphilis
      outside the Americas are taken into account, the place of origin remains
      unsolved. Finally, the endeavor of joining paleopathology and phylogenetics
      proved to be a fruitful and promising approach for the study of infectious
      diseases.

PMID- 20052269
TI  - The liver plays a major role in clearance and destruction of blood
      trypomastigotes in Trypanosoma cruzi chronically infected mice.
AB  - Intravenous challenge with Trypanosoma cruzi can be used to investigate the
      process and consequences of blood parasite clearance in experimental Chagas
      disease. One hour after intravenous challenge of chronically infected mice with
      5x10(6) trypomastigotes, the liver constituted a major site of parasite
      accumulation, as revealed by PCR. Intact parasites and/or parasite remnants were
      visualized at this time point scattered in the liver parenchyma. Moreover, at
      this time, many of liver-cleared parasites were viable, as estimated by the
      frequency of positive cultures, which considerably diminished after 48 h.
      Following clearance, the number of infiltrating cells in the hepatic tissue
      notably increased: initially (at 24 h) as diffuse infiltrates affecting the whole
      parenchyma, and at 48 h, in the form of large focal infiltrates in both the
      parenchyma and perivascular spaces. Phenotypic characterization of liver
      infiltrating cells 24 h after challenge revealed an increase in Mac1(+), CD8(+)
      and CD4(+) cells, followed by natural killer (NK) cells. As evidence that liver
      infiltrating CD4(+) and CD8(+) cells were activated, increased frequencies of
      CD69(+)CD8(+), CD69(+)CD4(+) and CD25(+)CD122(+)CD4(+) cells were observed at 24
      and 48 h after challenge, and of CD25(-)CD122(+)CD4(+) cells at 48 h. The major
      role of CD4(+) cells in liver protection was suggested by data showing a very
      high frequency of interferon (IFN)-gamma-producing CD4(+) cells 24 h after
      challenge. In contrast, liver CD8(+) cells produced little IFN-gamma, even though
      they showed an enhanced potential for secreting this cytokine, as revealed by in
      vitro T cell receptor (TCR) stimulation. Confirming the effectiveness of the
      liver immune response in blood parasite control during the chronic phase of
      infection, no live parasites were detected in this organ 7 days after challenge.

PMID- 20052270
TI  - Modeling mitochondrial bioenergetics with integrated volume dynamics.
AB  - Mathematical models of mitochondrial bioenergetics provide powerful analytical
      tools to help interpret experimental data and facilitate experimental design for
      elucidating the supporting biochemical and physical processes. As a next step
      towards constructing a complete physiologically faithful mitochondrial
      bioenergetics model, a mathematical model was developed targeting the cardiac
      mitochondrial bioenergetic based upon previous efforts, and corroborated using
      both transient and steady state data. The model consists of several modified rate
      functions of mitochondrial bioenergetics, integrated calcium dynamics and a
      detailed description of the K(+)-cycle and its effect on mitochondrial
      bioenergetics and matrix volume regulation. Model simulations were used to fit 42
      adjustable parameters to four independent experimental data sets consisting of 32
      data curves. During the model development, a certain network topology had to be
      in place and some assumptions about uncertain or unobserved experimental factors
      and conditions were explicitly constrained in order to faithfully reproduce all
      the data sets. These realizations are discussed, and their necessity helps
      contribute to the collective understanding of the mitochondrial bioenergetics.

PMID- 20052271
TI  - Disentangling direct from indirect co-evolution of residues in protein
      alignments.
AB  - Predicting protein structure from primary sequence is one of the ultimate
      challenges in computational biology. Given the large amount of available sequence
      data, the analysis of co-evolution, i.e., statistical dependency, between columns
      in multiple alignments of protein domain sequences remains one of the most
      promising avenues for predicting residues that are contacting in the structure. A
      key impediment to this approach is that strong statistical dependencies are also
      observed for many residue pairs that are distal in the structure. Using a
      comprehensive analysis of protein domains with available three-dimensional
      structures we show that co-evolving contacts very commonly form chains that
      percolate through the protein structure, inducing indirect statistical
      dependencies between many distal pairs of residues. We characterize the
      distributions of length and spatial distance traveled by these co-evolving
      contact chains and show that they explain a large fraction of observed
      statistical dependencies between structurally distal pairs. We adapt a recently
      developed Bayesian network model into a rigorous procedure for disentangling
      direct from indirect statistical dependencies, and we demonstrate that this
      method not only successfully accomplishes this task, but also allows contacts
      with weak statistical dependency to be detected. To illustrate how additional
      information can be incorporated into our method, we incorporate a phylogenetic
      correction, and we develop an informative prior that takes into account that the
      probability for a pair of residues to contact depends strongly on their primary
      sequence distance and the amount of conservation that the corresponding columns
      in the multiple alignment exhibit. We show that our model including these
      extensions dramatically improves the accuracy of contact prediction from multiple
      sequence alignments.

PMID- 20052273
TI  - The evolution of the epidemic of charcoal-burning suicide in Taiwan: a spatial
      and temporal analysis.
AB  - BACKGROUND: An epidemic of carbon monoxide poisoning suicide by burning barbecue
      charcoal has occurred in East Asia in the last decade. We investigated the
      spatial and temporal evolution of the epidemic to assess its impact on the
      epidemiology of suicide in Taiwan. METHODS AND FINDINGS: Age-standardised rates
      of suicide and undetermined death by charcoal burning were mapped across
      townships (median population aged 15 y or over = 27,000) in Taiwan for the
      periods 1999-2001, 2002-2004, and 2005-2007. Smoothed standardised mortality
      ratios of charcoal-burning and non-charcoal-burning suicide and undetermined
      death across townships were estimated using Bayesian hierarchical models. Trends
      in overall and method-specific rates were compared between urban and rural areas
      for the period 1991-2007. The epidemic of charcoal-burning suicide in Taiwan
      emerged more prominently in urban than rural areas, without a single point of
      origin, and rates of charcoal-burning suicide remained highest in the
      metropolitan regions throughout the epidemic. The rural excess in overall suicide
      rates prior to 1998 diminished as rates of charcoal-burning suicide increased to
      a greater extent in urban than rural areas. CONCLUSIONS: The charcoal-burning
      epidemic has altered the geography of suicide in Taiwan. The observed pattern and
      its changes in the past decade suggest that widespread media coverage of this
      suicide method and easy access to barbecue charcoal may have contributed to the
      epidemic. Prevention strategies targeted at these factors, such as introducing
      and enforcing guidelines on media reporting and restricting access to charcoal,
      may help tackle the increase of charcoal-burning suicides. Please see later in
      the article for the Editors' Summary.

PMID- 20052272
TI  - Ultradeep sequencing of a human ultraconserved region reveals somatic and
      constitutional genomic instability.
AB  - Early detection of cancer-associated genomic instability is crucial, particularly
      in tumour types in which this instability represents the essential underlying
      mechanism of tumourigenesis. Currently used methods require the presence of
      already established neoplastic cells because they only detect clonal mutations.
      In principle, parallel sequencing of single DNA filaments could reveal the early
      phases of tumour initiation by detecting low-frequency mutations, provided an
      adequate depth of coverage and an effective control of the experimental error. We
      applied ultradeep sequencing to estimate the genomic instability of individuals
      with hereditary non-polyposis colorectal cancer (HNPCC). To overcome the
      experimental error, we used an ultraconserved region (UCR) of the human genome as
      an internal control. By comparing the mutability outside and inside the UCR, we
      observed a tendency of the ultraconserved element to accumulate significantly
      fewer mutations than the flanking segments in both neoplastic and nonneoplastic
      HNPCC samples. No difference between the two regions was detectable in cells from
      healthy donors, indicating that all three HNPCC samples have mutation rates
      higher than the healthy genome. This is the first, to our knowledge, direct
      evidence of an intrinsic genomic instability of individuals with heterozygous
      mutations in mismatch repair genes, and constitutes the proof of principle for
      the development of a more sensitive molecular assay of genomic instability.

PMID- 20052274
TI  - Are patents impeding medical care and innovation?
AB  - BACKGROUND TO THE DEBATE: Pharmaceutical and medical device manufacturers argue
      that the current patent system is crucial for stimulating research and
      development (R&D), leading to new products that improve medical care. The
      financial return on their investments that is afforded by patent protection, they
      claim, is an incentive toward innovation and reinvestment into further R&D. But
      this view has been challenged in recent years. Many commentators argue that
      patents are stifling biomedical research, for example by preventing researchers
      from accessing patented materials or methods they need for their studies. Patents
      have also been blamed for impeding medical care by raising prices of essential
      medicines, such as antiretroviral drugs, in poor countries. This debate examines
      whether and how patents are impeding health care and innovation.

PMID- 20052275
TI  - CRF1-R activation of the dynorphin/kappa opioid system in the mouse basolateral
      amygdala mediates anxiety-like behavior.
AB  - Stress is a complex human experience and having both rewarding and aversive
      motivational properties. The adverse effects of stress are well documented, yet
      many of underlying mechanisms remain unclear and controversial. Here we report
      that the anxiogenic properties of stress are encoded by the endogenous opioid
      peptide dynorphin acting in the basolateral amygdala. Using pharmacological and
      genetic approaches, we found that the anxiogenic-like effects of Corticotropin
      Releasing Factor (CRF) were triggered by CRF(1)-R activation of the
      dynorphin/kappa opioid receptor (KOR) system. Central CRF administration
      significantly reduced the percent open-arm time in the elevated plus maze (EPM).
      The reduction in open-arm time was blocked by pretreatment with the KOR
      antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the
      endogenous KOR ligand dynorphin. The CRF(1)-R agonist stressin 1 also
      significantly reduced open-arm time in the EPM, and this decrease was blocked by
      norBNI. In contrast, the selective CRF(2)-R agonist urocortin III did not affect
      open arm time, and mice lacking CRF(2)-R still showed an increase in anxiety-like
      behavior in response to CRF injection. However, CRF(2)-R knockout animals did not
      develop CRF conditioned place aversion, suggesting that CRF(1)-R activation may
      mediate anxiety and CRF(2)-R may encode aversion. Using a phosphoselective
      antibody (KORp) to identify sites of dynorphin action, we found that CRF
      increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype,
      but not in mice pretreated with the selective CRF(1)-R antagonist, antalarmin.
      Consistent with the concept that acute stress or CRF injection-induced anxiety
      was mediated by dynorphin release in the BLA, local injection of norBNI blocked
      the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI
      injection in a nearby thalamic nucleus did not. The intersection of stress
      induced CRF and the dynorphin/KOR system in the BLA was surprising, and these
      results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced
      anxiety behaviors and aversive behaviors via different mechanisms.

PMID- 20052276
TI  - The Association between Primary Endometrioid Carcinoma of the Ovary and
      Synchronous Malignancy of the Endometrium.
AB  - Objective. Ovarian and endometrial cancers coincide rather frequently in the same
      patient. Few data are available on the involvement of the specific morphological
      subtypes. To identify histological pathways in the synchronous occurrence, a
      population-based study was performed in The Netherlands. Methods. Using the
      national pathology database (PALGA) information of ovarian cancers and of earlier
      or later cancer in the endometrium was obtained. 5366 Patients were identified
      with primary malignant epithelial or borderline malignancy. Results. In 157 cases
      (2.9%) a new primary malignancy in the endometrium was diagnosed (146 within 1
      year). The ratio of observed versus expected number of synchronous malignancy in
      the endometrium was estimated at 3.6 (95% CI: 2.7-4.7). Among 460 ovarian
      endometrioid carcinoma patients 53 cases showed a second primary endometrial
      cancer; 40 out of these 53 cases (75.5%) showed at both organ sites an
      endometrioid adenocarcinoma. Conclusion. These findings suggest an important role
      for the endometrioid subtype and prompt to mechanism-based studies incorporating
      molecular techniques.

PMID- 20052277
TI  - The global health system: actors, norms, and expectations in transition.
AB  - In the first in a series of four articles highlighting the changing nature of
      global health institutions, Nicole Szlezak and colleagues outline the origin and
      aim of the series.

PMID- 20052278
TI  - Relationship between vehicle emissions laws and incidence of suicide by motor
      vehicle exhaust gas in Australia, 2001-06: an ecological analysis.
AB  - BACKGROUND: Globally, suicide accounts for 5.2% of deaths among persons aged 15
      to 44 years and its incidence is rising. In Australia, suicide rates peaked in
      1997 and have been declining since. A substantial part of that decline stems from
      a plunge in suicides by one particular method: asphyxiation by motor vehicle
      exhaust gas (MVEG). Although MVEG remains the second most common method of
      suicide in Australia, its incidence decreased by nearly 70% in the decade to
      2006. The extent to which this phenomenon has been driven by national laws in
      1986 and 1999 that lowered permissible levels of carbon monoxide (CO) emissions
      is unknown. The objective of this ecological study was to test the relationship
      by investigating whether areas of Australia with fewer noxious vehicles per
      capita experienced lower rates of MVEG suicide. METHODS AND FINDINGS: We merged
      data on MVEG suicides in Australia (2001-06) with data on the number and age of
      vehicles in the national fleet, as well as socio-demographic data from the
      national census. Poisson regression was used to analyse the relationship between
      the incidence of suicide within two levels of geographical area--postcodes and
      statistical subdivisions (SSDs)--and the population density of pre-1986 and pre
      1999 passenger vehicles in those areas. (There was a mean population of 8,302
      persons per postcode in the study dataset and 87,413 persons per SSD.) The annual
      incidence of MVEG suicides nationwide decreased by 57% (from 2.6 per 100,000 in
      2001 to 1.1 in 2006) during the study period; the population density of pre-1986
      and pre-1999 vehicles decreased by 55% (from 14.2 per 100 persons in 2001 to 6.4
      in 2006) and 26% (from 44.5 per 100 persons in 2001 to 32.9 in 2006),
      respectively. Area-level regression analysis showed that the suicide rates were
      significantly and positively correlated with the presence of older vehicles. A
      percentage point decrease in the population density of pre-1986 vehicles was
      associated with a 6% decrease (rate ratio [RR] = 1.06; 95% confidence interval
      [CI] 1.05-1.08) in the incidence of MVEG suicide within postcode areas; a
      percentage point decrease in the population density of pre-1999 vehicles was
      associated with a 3% decrease (RR = 1.03; 95% CI 1.02-1.04) in the incidence of
      MVEG suicide. CONCLUSIONS: Areas of Australia with fewer vehicles predating
      stringent CO emission laws experience lower rates of MVEG suicide. Although those
      emission laws were introduced primarily for environmental reasons, countries that
      lack them may miss the benefits of a serendipitous suicide prevention strategy.
      Please see later in the article for the Editors' Summary.

PMID- 20052279
TI  - Biochemical warfare on the reef: the role of glutathione transferases in consumer
      tolerance of dietary prostaglandins.
AB  - BACKGROUND: Despite the profound variation among marine consumers in tolerance
      for allelochemically-rich foods, few studies have examined the biochemical
      adaptations underlying diet choice. Here we examine the role of glutathione S
      transferases (GSTs) in the detoxification of dietary allelochemicals in the
      digestive gland of the predatory gastropod Cyphoma gibbosum, a generalist
      consumer of gorgonian corals. Controlled laboratory feeding experiments were used
      to investigate the influence of gorgonian diet on Cyphoma GST activity and
      isoform expression. Gorgonian extracts and semi-purified fractions were also
      screened to identify inhibitors and possible substrates of Cyphoma GSTs. In
      addition, we investigated the inhibitory properties of prostaglandins (PGs)
      structurally similar to antipredatory PGs found in high concentrations in the
      Caribbean gorgonian Plexaura homomalla. PRINCIPAL FINDINGS: Cyphoma GST subunit
      composition was invariant and activity was constitutively high regardless of
      gorgonian diet. Bioassay-guided fractionation of gorgonian extracts revealed that
      moderately hydrophobic fractions from all eight gorgonian species examined
      contained putative GST substrates/inhibitors. LC-MS and NMR spectral analysis of
      the most inhibitory fraction from P. homomalla subsequently identified
      prostaglandin A(2) (PGA(2)) as the dominant component. A similar screening of
      commercially available prostaglandins in series A, E, and F revealed that those
      prostaglandins most abundant in gorgonian tissues (e.g., PGA(2)) were also the
      most potent inhibitors. In vivo estimates of PGA(2) concentration in digestive
      gland tissues calculated from snail grazing rates revealed that Cyphoma GSTs
      would be saturated with respect to PGA(2) and operating at or near physiological
      capacity. SIGNIFICANCE: The high, constitutive activity of Cyphoma GSTs is likely
      necessitated by the ubiquitous presence of GST substrates and/or inhibitors in
      this consumer's gorgonian diet. This generalist's GSTs may operate as 'all
      purpose' detoxification enzymes, capable of conjugating or sequestering a broad
      range of lipophilic gorgonian compounds, thereby allowing this predator to
      exploit a range of chemically-defended prey, resulting in a competitive dietary
      advantage for this species.

PMID- 20052280
TI  - Staphylococcus epidermidis antimicrobial delta-toxin (phenol-soluble modulin
      gamma) cooperates with host antimicrobial peptides to kill group A Streptococcus.
AB  - Antimicrobial peptides play an important role in host defense against pathogens.
      Recently, phenol-soluble modulins (PSMs) from Staphylococcus epidermidis (S.
      epidermidis) were shown to interact with lipid membranes, form complexes, and
      exert antimicrobial activity. Based on the abundance and innocuity of the
      cutaneous resident S. epidermidis, we hypothesized that their PSMs contribute to
      host defense. Here we show that S. epidermidis delta-toxin (PSMgamma) is normally
      present in the epidermis and sparsely in the dermis of human skin using
      immunohistochemistry. Synthetic delta-toxin interacted with neutrophil
      extracellular traps (NETs) and colocalized with cathelicidin while also inducing
      NET formation in human neutrophils. In antimicrobial assays against Group A
      Streptococcus (GAS), delta-toxin cooperated with CRAMP, hBD2, and hBD3. In whole
      blood, addition of delta-toxin exerted a bacteriostatic effect on GAS, and in
      NETs, delta-toxin increased their killing capacity against this pathogen.
      Coimmunoprecipitation and tryptophan spectroscopy demonstrated direct binding of
      delta-toxin to host antimicrobial peptides LL-37, CRAMP, hBD2, and hBD3. Finally,
      in a mouse wound model, GAS survival was reduced (along with Mip-2 cytokine
      levels) when the wounds were pretreated with delta-toxin. Thus, these data
      suggest that S. epidermidis-derived delta-toxin cooperates with the host-derived
      antimicrobial peptides in the innate immune system to reduce survival of an
      important human bacterial pathogen.

PMID- 20052281
TI  - Retrieval of the vacuolar H-ATPase from phagosomes revealed by live cell imaging.
AB  - BACKGROUND: The vacuolar H+-ATPase, or V-ATPase, is a highly-conserved multi
      subunit enzyme that transports protons across membranes at the expense of ATP.
      The resulting proton gradient serves many essential functions, among them
      energizing transport of small molecules such as neurotransmitters, and acidifying
      organelles such as endosomes. The enzyme is not present in the plasma membrane
      from which a phagosome is formed, but is rapidly delivered by fusion with
      endosomes that already bear the V-ATPase in their membranes. Similarly, the
      enzyme is thought to be retrieved from phagosome membranes prior to exocytosis of
      indigestible material, although that process has not been directly visualized.
      METHODOLOGY: To monitor trafficking of the V-ATPase in the phagocytic pathway of
      Dictyostelium discoideum, we fed the cells yeast, large particles that maintain
      their shape during trafficking. To track pH changes, we conjugated the yeast with
      fluorescein isothiocyanate. Cells were labeled with VatM-GFP, a fluorescently
      tagged transmembrane subunit of the V-ATPase, in parallel with stage-specific
      endosomal markers or in combination with mRFP-tagged cytoskeletal proteins.
      PRINCIPAL FINDINGS: We find that the V-ATPase is commonly retrieved from the
      phagosome membrane by vesiculation shortly before exocytosis. However, if the
      cells are kept in confined spaces, a bulky phagosome may be exocytosed
      prematurely. In this event, a large V-ATPase-rich vacuole coated with actin
      typically separates from the acidic phagosome shortly before exocytosis. This
      vacuole is propelled by an actin tail and soon acquires the properties of an
      early endosome, revealing an unexpected mechanism for rapid recycling of the V
      ATPase. Any V-ATPase that reaches the plasma membrane is also promptly retrieved.
      CONCLUSIONS/SIGNIFICANCE: Thus, live cell microscopy has revealed both a usual
      route and alternative means of recycling the V-ATPase in the endocytic pathway.

PMID- 20052282
TI  - 2-D structure of the A region of Xist RNA and its implication for PRC2
      association.
AB  - In placental mammals, inactivation of one of the X chromosomes in female cells
      ensures sex chromosome dosage compensation. The 17 kb non-coding Xist RNA is
      crucial to this process and accumulates on the future inactive X chromosome. The
      most conserved Xist RNA region, the A region, contains eight or nine repeats
      separated by U-rich spacers. It is implicated in the recruitment of late
      inactivated X genes to the silencing compartment and likely in the recruitment of
      complex PRC2. Little is known about the structure of the A region and more
      generally about Xist RNA structure. Knowledge of its structure is restricted to
      an NMR study of a single A repeat element. Our study is the first experimental
      analysis of the structure of the entire A region in solution. By the use of
      chemical and enzymatic probes and FRET experiments, using oligonucleotides
      carrying fluorescent dyes, we resolved problems linked to sequence redundancies
      and established a 2-D structure for the A region that contains two long stem-loop
      structures each including four repeats. Interactions formed between repeats and
      between repeats and spacers stabilize these structures. Conservation of the
      spacer terminal sequences allows formation of such structures in all sequenced
      Xist RNAs. By combination of RNP affinity chromatography, immunoprecipitation
      assays, mass spectrometry, and Western blot analysis, we demonstrate that the A
      region can associate with components of the PRC2 complex in mouse ES cell nuclear
      extracts. Whilst a single four-repeat motif is able to associate with components
      of this complex, recruitment of Suz12 is clearly more efficient when the entire A
      region is present. Our data with their emphasis on the importance of inter-repeat
      pairing change fundamentally our conception of the 2-D structure of the A region
      of Xist RNA and support its possible implication in recruitment of the PRC2
      complex.

PMID- 20052283
TI  - Mutations in the gene encoding the ancillary pilin subunit of the Streptococcus
      suis srtF cluster result in pili formed by the major subunit only.
AB  - Pili have been shown to contribute to the virulence of different Gram-positive
      pathogenic species. Among other critical steps of bacterial pathogenesis, these
      structures participate in adherence to host cells, colonization and systemic
      virulence. Recently, the presence of at least four discrete gene clusters
      encoding putative pili has been revealed in the major swine pathogen and emerging
      zoonotic agent Streptococcus suis. However, pili production by this species has
      not yet been demonstrated. In this study, we investigated the functionality of
      one of these pili clusters, known as the srtF pilus cluster, by the construction
      of mutant strains for each of the four genes of the cluster as well as by the
      generation of antibodies against the putative pilin subunits. Results revealed
      that the S. suis serotype 2 strain P1/7, as well as several other highly virulent
      invasive S. suis serotype 2 isolates express pili from this cluster. However, in
      most cases tested, and as a result of nonsense mutations at the 5' end of the
      gene encoding the minor pilin subunit (a putative adhesin), pili were formed by
      the major pilin subunit only. We then evaluated the role these pili play in S.
      suis virulence. Abolishment of the expression of srtF cluster-encoded pili did
      not result in impaired interactions of S. suis with porcine brain microvascular
      endothelial cells. Furthermore, non-piliated mutants were as virulent as the wild
      type strain when evaluated in a murine model of S. suis sepsis. Our results show
      that srtF cluster-encoded, S. suis pili are atypical compared to other Gram
      positive pili. In addition, since the highly virulent strains under investigation
      are unlikely to produce other pili, our results suggest that pili might be
      dispensable for critical steps of the S. suis pathogenesis of infection.

PMID- 20052284
TI  - Ligand depletion in vivo modulates the dynamic range and cooperativity of signal
      transduction.
AB  - Biological signal transduction commonly involves cooperative interactions in the
      binding of ligands to their receptors. In many cases, ligand concentrations in
      vivo are close to the value of the dissociation constant of their receptors,
      resulting in the phenomenon of ligand depletion. Using examples based on
      rotational bias of bacterial flagellar motors and calcium binding to mammalian
      calmodulin, we show that ligand depletion diminishes cooperativity and broadens
      the dynamic range of sensitivity to the signaling ligand. As a result, the same
      signal transducer responds to different ranges of signal with various degrees of
      cooperativity according to its effective cellular concentration. Hence, results
      from in vitro dose-response analyses cannot be applied directly to understand
      signaling in vivo. Moreover, the receptor concentration is revealed to be a key
      element in controlling signal transduction and we propose that its modulation
      constitutes a new way of controlling sensitivity to signals. In addition, through
      an analysis of the allosteric enzyme aspartate transcarbamylase, we demonstrate
      that the classical Hill coefficient is not appropriate for characterizing the
      change in conformational state upon ligand binding to an oligomeric protein
      (equivalent to a dose-response curve), because it ignores the cooperativity of
      the conformational change for the corresponding equivalent monomers, which are
      generally characterized by a Hill coefficient . Therefore, we propose a new index
      of cooperativity based on the comparison of the properties of oligomers and their
      equivalent monomers.

PMID- 20052285
TI  - Chaperone requirements for biosynthesis of the trypanosome variant surface
      glycoprotein.
AB  - BACKGROUND: Trypanosoma brucei does not respond transcriptionally to several
      endoplasmic reticulum (ER) stress conditions, including tunicamycin or
      dithiothreitol, indicating the absence of a conventional unfolded protein
      response. This suggests divergent mechanisms for quality control (QC) of ER
      protein folding and export may be present in trypanosomes. As the variant surface
      glycoprotein (VSG) represents approximately 90% of trypanosome plasma membrane
      protein, it is possible that VSG has evolved to fold efficiently to minimize ER
      folding burden. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate the presence of a
      QC system by pharmacological inhibition of the trypanosome 26S proteasome. This
      indicates active proteasome-mediated VSG turnover as approximately 2.5 fold more
      VSG is recovered from cell lysates following MG132 inhibition. An in silico scan
      of the trypanosome genome identified 28 open reading frames likely to encode
      polypeptides participating in ER nascent chain maturation. By RNA interference we
      monitored the importance of these gene products to proliferation, VSG abundance
      and cell morphology. 68% of the cohort were required for normal proliferation,
      and depletion of most of these factors resulted in increased VSG abundance,
      suggesting involvement in ERQC and degradation. CONCLUSIONS/SIGNIFICANCE: The
      retention of genes for, and the involvement of many gene products in, VSG folding
      indicates a substantial complexity within the pathways required to perform this
      role. Counterintuitively, for a super-abundant antigen VSG is apparently made in
      excess. The biosynthetic excess VSG appears to be turned over efficiently by the
      proteasome, implying that considerable VSG is rejected by the trypanosome ERQC
      mechanism. Accordingly, the VSG polypeptide is not well optimized for folding, as
      only approximately 30% attains the native state. Finally as much of the core ERQC
      system is functionally conserved in trypanosomes, the pathway has an ancient
      evolutionary origin, and was present in the last common eukaryotic ancestor.

PMID- 20052286
TI  - Dissemination of spotted fever rickettsia agents in Europe by migrating birds.
AB  - Migratory birds are known to play a role as long-distance vectors for many
      microorganisms. To investigate whether this is true of rickettsial agents as
      well, we characterized tick infestation and gathered ticks from 13,260 migratory
      passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from
      these birds and the extracted DNA from 957 of them was available for analyses.
      The DNA was assayed for detection of Rickettsia spp. using real-time PCR,
      followed by DNA sequencing for species identification. Rickettsia spp. organisms
      were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever
      rickettsia associated with human infections, was predominant among the PCR
      positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and
      ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic
      agent of Mediterranean spotted fever-like illness, previously described in
      southern Europe as well as to the Rickettsia sp.IrITA3 strain. For 15 (1.4%) of
      the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to
      Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia
      heilongjiangensis, all closely phylogenetically related, the former previously
      found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes
      spp. ticks. The infestation prevalence of ticks infected with rickettsial
      organisms was four times higher among ground foraging birds than among other bird
      species, but the two groups were equally competent in transmitting Rickettsia
      species. The birds did not seem to serve as reservoir hosts for Rickettsia spp.,
      but in one case it seems likely that the bird was rickettsiemic and that the
      ticks had acquired the bacteria from the blood of the bird. In conclusion,
      migratory passerine birds host epidemiologically important vector ticks and
      Rickettsia species and contribute to the geographic distribution of spotted fever
      rickettsial agents and their diseases.

PMID- 20052287
TI  - Poised transcription factories prime silent uPA gene prior to activation.
AB  - The position of genes in the interphase nucleus and their association with
      functional landmarks correlate with active and/or silent states of expression.
      Gene activation can induce chromatin looping from chromosome territories (CTs)
      and is thought to require de novo association with transcription factories. We
      identify two types of factory: "poised transcription factories," containing RNA
      polymerase II phosphorylated on Ser5, but not Ser2, residues, which differ from
      "active factories" associated with phosphorylation on both residues. Using the
      urokinase-type plasminogen activator (uPA) gene as a model system, we find that
      this inducible gene is predominantly associated with poised (S5p(+)S2p(-))
      factories prior to activation and localized at the CT interior. Shortly after
      induction, the uPA locus is found associated with active (S5p(+)S2p(+)) factories
      and loops out from its CT. However, the levels of gene association with poised or
      active transcription factories, before and after activation, are independent of
      locus positioning relative to its CT. RNA-FISH analyses show that, after
      activation, the uPA gene is transcribed with the same frequency at each CT
      position. Unexpectedly, prior to activation, the uPA loci internal to the CT are
      seldom transcriptionally active, while the smaller number of uPA loci found
      outside their CT are transcribed as frequently as after induction. The
      association of inducible genes with poised transcription factories prior to
      activation is likely to contribute to the rapid and robust induction of gene
      expression in response to external stimuli, whereas gene positioning at the CT
      interior may be important to reinforce silencing mechanisms prior to induction.

PMID- 20052288
TI  - Role of GD3-CLIPR-59 association in lymphoblastoid T cell apoptosis triggered by
      CD95/Fas.
AB  - We previously found that a directional movement of the raft component GD3 towards
      mitochondria, by its association with microtubules, was mandatory to late
      apoptogenic events triggered by CD95/Fas. Since CLIPR-59, CLIP-170-related
      protein, has recently been identified as a microtubule binding protein associated
      with lipid rafts, we analyzed the role of GD3-CLIPR-59 association in
      lymphoblastoid T cell apoptosis triggered by CD95/Fas. To test whether CLIPR-59
      could play a role at the raft-microtubule junction, we performed a series of
      experiments by using immunoelectron microscopy, static or flow cytometry and
      biochemical analyses. We first assessed the presence of CLIPR-59 molecule in
      lymphoblastoid T cells (CEM). Then, we demonstrated that GD3-microtubule
      interaction occurs via CLIPR-59 and takes place at early time points after
      CD95/Fas ligation, preceding the association GD3-tubulin. GD3-CLIPR-59
      association was demonstrated by fluorescence resonance energy transfer (FRET)
      analysis. The key role of CLIPR-59 in this dynamic process was clarified by the
      observation that silencing CLIPR-59 by siRNA affected the kinetics of GD3-tubulin
      association, spreading of GD3 towards mitochondria and apoptosis execution. We
      find that CLIPR-59 may act as a typical chaperone, allowing a prompt interaction
      between tubulin and the raft component GD3 during cell apoptosis triggered by
      CD95/Fas. On the basis of the suggested role of lipid rafts in conveying pro
      apoptotic signals these results disclose new perspectives in the understanding of
      the mechanisms by which raft-mediated pro-apoptotic signals can directionally
      reach their target, i.e. the mitochondria, and trigger apoptosis execution.

PMID- 20052289
TI  - Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates
      expression of human telomerase reverse transcriptase (hTERT) gene.
AB  - BACKGROUND: Increased levels of interferon (IFN)-inducible IFI16 protein (encoded
      by the IFI16 gene located at 1q22) in human normal prostate epithelial cells and
      diploid fibroblasts (HDFs) are associated with the onset of cellular senescence.
      However, the molecular mechanisms by which the IFI16 protein contributes to
      cellular senescence-associated cell growth arrest remain to be elucidated. Here,
      we report that increased levels of IFI16 protein in normal HDFs and in HeLa cells
      negatively regulate the expression of human telomerase reverse transcriptase
      (hTERT) gene. METHODOLOGY/PRINCIPAL FINDINGS: We optimized conditions for real
      time PCR, immunoblotting, and telomere repeat amplification protocol (TRAP)
      assays to detect relatively low levels of hTERT mRNA, protein, and telomerase
      activity that are found in HDFs. Using the optimized conditions, we report that
      treatment of HDFs with inhibitors of cell cycle progression, such as aphidicolin
      or CGK1026, which resulted in reduced steady-state levels of IFI16 mRNA and
      protein, was associated with increases in hTERT mRNA and protein levels and
      telomerase activity. In contrast, knockdown of IFI16 expression in cells
      increased the expression of c-Myc, a positive regulator of hTERT expression.
      Additionally, over-expression of IFI16 protein in cells inhibited the c-Myc
      mediated stimulation of the activity of hTERT-luc-reporter and reduced the steady
      state levels of c-Myc and hTERT. CONCLUSIONS/SIGNIFICANCE: These data
      demonstrated that increased levels of IFI16 protein in HDFs down-regulate the
      expression of hTERT gene. Our observations will serve basis to understand how
      increased cellular levels of the IFI16 protein may contribute to certain aging
      dependent diseases.

PMID- 20052290
TI  - HSF1-controlled and age-associated chaperone capacity in neurons and muscle cells
      of C. elegans.
AB  - Protein stability under changing conditions is of vital importance for the cell
      and under the control of a fine-tuned network of molecular chaperones. Aging and
      age-related neurodegenerative diseases are directly associated with enhanced
      protein instability. Employing C. elegans expressing GFP-tagged luciferase as a
      reporter for evaluation of protein stability we show that the chaperoning
      strategy of body wall muscle cells and neurons is significantly different and
      that both are differently affected by aging. Muscle cells of young worms are
      largely resistant to heat stress, which is directly mediated by the stress
      response controlled through Heat Shock Transcription Factor 1. During recovery
      following heat stress the ability to refold misfolded proteins is missing. Young
      neurons are highly susceptible to chronic heat stress, but show a high potency to
      refold or disaggregate proteins during subsequent recovery. The particular
      proteome instability in neurons results from a delayed induction of the heat
      shock response. In aged neurons protein stability is increased during heat
      stress, whereas muscle cells show enhanced protein instability due to a
      deteriorated heat shock response. An efficient refolding activity is absent in
      both aged tissues. These results provide molecular insights into the differential
      protein stabilization capacity in different tissues and during aging.

PMID- 20052291
TI  - Brain activation in response to visceral stimulation in rats with amygdala
      implants of corticosterone: an FMRI study.
AB  - BACKGROUND: Although visceral pain of gastrointestinal (GI) origin is the major
      complaint in patients with irritable bowel syndrome (IBS) it remains poorly
      understood. Brain imaging studies suggest a defect in brain-gut communication in
      IBS with a greater activation of central arousal circuits including the amygdala.
      Previously, we found that stereotaxic implantation of corticosterone (CORT) onto
      the amygdala in rats induced anxiety and colonic hypersensitivity. In the present
      study we used functional magnetic resonance imaging (fMRI) to identify specific
      brain sites activated in a rat model characterized by anxiety and colonic
      hypersensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Anesthetized male rats received
      micropellets (30 microg each) of either CORT or cholesterol (CHOL), to serve as a
      control, implanted stereotaxically on the dorsal margin of each amygdala. Seven
      days later, rats were anesthetized and placed in the fMRI magnet (7T). A series
      of isobaric colorectal balloon distensions (CRD - 90s 'off', 30s 'on', 8
      replicates) at two pressures (40 and 60 mmHg) were performed in a standard block
      design. Cross correlation statistical analysis was used to determine significant
      differences between distended and non-distended states in CORT and CHOL-treated
      animals. Analysis of the imaging data demonstrated greater overall brain
      activation in response to CRD in rats with CORT implants compared to CHOL
      controls. Additionally, CORT implants produced significant positive bilateral
      increases in MRI signal in response to CRD in specific nuclei known as
      integration sites important in anxiety and pain perception. CONCLUSIONS AND
      SIGNIFICANCE: These data indicate that chronic exposure of the amygdala to
      elevated levels of CORT enhances overall brain activation in response to CRD, and
      identified other specific brain regions activated in response to mechanical
      distension of the colon. These results demonstrate the feasibility of performing
      fMRI imaging in a rodent model that supports clinical observations in IBS
      patients with enhanced amygdala activation and symptomatology of abdominal pain
      and anxiety.

PMID- 20052292
TI  - Presynaptic external calcium signaling involves the calcium-sensing receptor in
      neocortical nerve terminals.
AB  - BACKGROUND: Nerve terminal invasion by an axonal spike activates voltage-gated
      channels, triggering calcium entry, vesicle fusion, and release of
      neurotransmitter. Ion channels activated at the terminal shape the presynaptic
      spike and so regulate the magnitude and duration of calcium entry. Consequently
      characterization of the functional properties of ion channels at nerve terminals
      is crucial to understand the regulation of transmitter release. Direct recordings
      from small neocortical nerve terminals have revealed that external [Ca(2+)]
      ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in
      neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify
      the first component in a presynaptic calcium signaling pathway.
      METHODOLOGY/PRINCIPAL FINDINGS: By combining genetic and pharmacological
      approaches with direct patch-clamp recordings from small acutely isolated
      neocortical nerve terminals we identify the extracellular calcium sensor. Our
      results show that the calcium-sensing receptor (CaSR), a previously identified G
      protein coupled receptor that is the mainstay in serum calcium homeostasis, is
      the extracellular calcium sensor in these acutely dissociated nerve terminals.
      The NSCC currents from reduced function mutant CaSR mice were less sensitive to
      changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist,
      reduced NSCC currents in direct terminal recordings in a dose-dependent and
      reversible manner. In contrast, glutamate and GABA did not affect the NSCC
      currents. CONCLUSIONS/SIGNIFICANCE: Our experiments identify CaSR as the first
      component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical
      terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of
      the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its
      entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in
      [Ca(2+)](o) and increase action potential duration by increasing NSCC activity,
      thereby attenuating the impact of decreases in [Ca(2+)](o) on release
      probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and
      provide presynaptic feedback that will alter brain excitability.

PMID- 20052293
TI  - Dendritic cell mediated delivery of plasmid DNA encoding LAMP/HIV-1 Gag fusion
      immunogen enhances T cell epitope responses in HLA DR4 transgenic mice.
AB  - This report describes the identification and bioinformatics analysis of HLA-DR4
      restricted HIV-1 Gag epitope peptides, and the application of dendritic cell
      mediated immunization of DNA plasmid constructs. BALB/c (H-2d) and HLA-DR4
      (DRA1*0101, DRB1*0401) transgenic mice were immunized with immature dendritic
      cells transfected by a recombinant DNA plasmid encoding the lysosome-associated
      membrane protein-1/HIV-1 Gag (pLAMP/gag) chimera antigen. Three immunization
      protocols were compared: 1) primary subcutaneous immunization with 1x10(5)
      immature dendritic cells transfected by electroporation with the pLAMP/gag DNA
      plasmid, and a second subcutaneous immunization with the naked pLAMP/gag DNA
      plasmid; 2) primary immunization as above, and a second subcutaneous immunization
      with a pool of overlapping peptides spanning the HIV-1 Gag sequence; and 3)
      immunization twice by subcutaneous injection of the pLAMP/gag DNA plasmid.
      Primary immunization with pLAMP/gag-transfected dendritic cells elicited the
      greatest number of peptide specific T-cell responses, as measured by ex vivo IFN
      gamma ELISpot assay, both in BALB/c and HLA-DR4 transgenic mice. The pLAMP/gag
      transfected dendritic cells prime and naked DNA boost immunization protocol also
      resulted in an increased apparent avidity of peptide in the ELISpot assay.
      Strikingly, 20 of 25 peptide-specific T-cell responses in the HLA-DR4 transgenic
      mice contained sequences that corresponded, entirely or partially to 18 of the 19
      human HLA-DR4 epitopes listed in the HIV molecular immunology database. Selection
      of the most conserved epitope peptides as vaccine targets was facilitated by
      analysis of their representation and variability in all reported sequences. These
      data provide a model system that demonstrates a) the superiority of immunization
      with dendritic cells transfected with LAMP/gag plasmid DNA, as compared to naked
      DNA, b) the value of HLA transgenic mice as a model system for the identification
      and evaluation of epitope-based vaccine strategies, and c) the application of
      variability analysis across reported sequences in public databases for selection
      of historically conserved HIV epitopes as vaccine targets.

PMID- 20052294
TI  - Alleviating Linear Ecological Bias and Optimal Design with Sub-sample Data.
AB  - In this paper, we illustrate that combining ecological data with subsample data
      in situations in which a linear model is appropriate provides three main
      benefits. First, by including the individual level subsample data, the biases
      associated with linear ecological inference can be eliminated. Second, by
      supplementing the subsample data with ecological data, the information about
      parameters will be increased. Third, we can use readily available ecological data
      to design optimal subsampling schemes, so as to further increase the information
      about parameters. We present an application of this methodology to the classic
      problem of estimating the effect of a college degree on wages. We show that
      combining ecological data with subsample data provides precise estimates of this
      value, and that optimal subsampling schemes (conditional on the ecological data)
      can provide good precision with only a fraction of the observations.

PMID- 20052295
TI  - K(alpha) x-ray emission characterization of 100 Hz, 15 mJ femtosecond laser
      system with high contrast ratio.
AB  - We report K(alpha) x-ray production with a high energy (110 mJ per pulse at 800
      nm before compression/15 mJ at 400 nm after compression), high repetition rate
      (100 Hz), and high pulse contrast (better than 10(-9) at 400 nm) laser system. To
      develop laser-based x-ray sources for biomedical imaging requires to use high
      energy and high-power ultra-fast laser system where compression is achieved under
      vacuum. Using this type of laser system, we demonstrate long-term stability of
      the x-ray yield, conversion efficiency higher than 1.5 x 10(-5) with a Mo target,
      and the x-ray spot size close to the optical focal spot. This high-repetition
      K(alpha) x-ray source can be very useful for x-ray phase-contrast imaging.

PMID- 20052296
TI  - Prostate brachytherapy seed localization using a mobile c-arm without tracking.
AB  - The success of prostate brachytherapy depends on the faithful delivery of a dose
      plan. In turn, intraoperative localization and visualization of the implanted
      radioactive brachytherapy seeds enables more proficient and informed adjustments
      to the executed plan during therapy. Prior work has demonstrated adequate seed
      reconstructions from uncalibrated mobile c-arms using either external tracking
      devices or image-based fiducials for c-arm pose determination. These alternatives
      are either time-consuming or interfere with the clinical flow of the surgery, or
      both. This paper describes a seed reconstruction approach that avoids both
      tracking devices and fiducials. Instead, it uses the preoperative dose plan in
      conjunction with a set of captured images to get initial estimates of the c-arm
      poses followed by an auto-focus technique using the seeds themselves as fiducials
      to refine the pose estimates. Intraoperative seed localization is achieved
      through iteratively solving for poses and seed correspondences across images and
      reconstructing the 3D implanted seeds. The feasibility of this approach was
      demonstrated through a series of simulations involving variable noise levels,
      seed densities, image separability and number of images. Preliminary results
      indicate mean reconstruction errors within 1.2 mm for noisy plans of 84 seeds or
      fewer. These are attained for additive noise whose standard deviation of the 3D
      mean error introduced to the plan to simulate the implant is within 3.2 mm.

PMID- 20052299
TI  - EXPERIENCES OF HIV/AIDS STIGMA OF PERSONS LIVING WITH HIV/AIDS AND NURSES
      INVOLVED IN THEIR CARE FROM FIVE AFRICAN COUNTRIES.
AB  - The concept of stigma has received significant attention in recent years in the
      HIV/AIDS literature. Although there is some change towards the positive, AIDS
      still remains a significantly stigmatized condition. AIDS stigma and
      discrimination continue to influence people living with and affected by HIV
      (PLWA), as well as their health-care providers. Unless stigma is conquered, the
      illness will not be defeated. Due to the burden that HIV/AIDS places on people
      living in Africa, a five-year project entitled Perceived AIDS Stigma: A
      Multinational African Study was undertaken. The focus of the first phase of this
      project was on exploring and describing the meaning and effect of stigma on PLWA
      from the experiences of PLWA and the nurses involved in their care in five
      African countries: Lesotho, Swaziland, Malawi, South Africa and Tanzania. An
      exploratory descriptive qualitative research design was used to explore and
      describe the experience of stigma through the critical incident method. Purposive
      voluntary sampling was utilized. Forty-three focus group discussions were held
      with respondents to relate incidences which they themselves observed, as well as
      those that they themselves experienced in the community and in families. The
      transcribed data was analyzed through the technique of open coding using the
      NVivo 2.0 analysis package. Three types of stigma (received stigma, internal
      stigma and associated stigma) and several dimensions for each of these types of
      stigma emerged from the data. Recommendations were made to pursue these findings
      further.

PMID- 20052297
TI  - Tissue Engineering with Nano-Fibrous Scaffolds.
AB  - Tissue Engineering is a rapidly evolving field in terms of cell source and
      scaffold fabrication. As the template for three dimensional tissue growth, the
      scaffold should emulate the native extracellular matrix, which is nano-fibrous.
      Currently, there are three basic techniques capable of generating nano-fibrous
      scaffolding: electrospinning, molecular self-assembly, and thermally induced
      phase separation. These scaffolds can then be further modified by various three
      dimensional surface modification techniques if necessary to more precisely
      emulate the native extracellular matrix. However, even without further
      modification, nano-fibrous scaffolds have been shown to have advantageous effects
      on cellular behavior and tissue formation when compared to more traditional types
      of scaffolding. This review focuses on the current state of tissue engineering
      with nano-fibrous scaffolding with particular emphasis on bone tissue
      engineering.

PMID- 20052300
TI  - A Parallel Adaptive Finite Element Method for the Simulation of Photon Migration
      with the Radiative-Transfer-Based Model.
AB  - Whole-body optical molecular imaging of mouse models in preclinical research is
      rapidly developing in recent years. In this context, it is essential and
      necessary to develop novel simulation methods of light propagation for optical
      imaging, especially when a priori knowledge, large-volume domain and a wide-range
      of optical properties need to be considered in the reconstruction algorithm. In
      this paper, we propose a three dimensional parallel adaptive finite element
      method with simplified spherical harmonics (SP(N)) approximation to simulate
      optical photon propagation in large-volumes of heterogenous tissues. The
      simulation speed is significantly improved by a posteriori parallel adaptive mesh
      refinement and dynamic mesh repartitioning. Compared with the diffusion equation
      and the Monte Carlo methods, the SP(N) method shows improved performance and the
      necessity of high-order approximation in heterogeneous domains. Optimal solver
      selection and time-costing analysis in real mouse geometry further improve the
      performance of the proposed algorithm and show the superiority of the proposed
      parallel adaptive framework for whole-body optical molecular imaging in murine
      models.

PMID- 20052301
TI  - What Are Grades Made Of?

PMID- 20052302
TI  - Error analysis and correction in wavefront reconstruction from the transport-of
      intensity equation.
AB  - Wavefront reconstruction from the transport-of-intensity equation (TIE) is a well
      posed inverse problem given smooth signals and appropriate boundary conditions.
      However, in practice experimental errors lead to an ill-condition problem. A
      quantitative analysis of the effects of experimental errors is presented in
      simulations and experimental tests. The relative importance of numerical,
      misalignment, quantization, and photodetection errors are shown. It is proved
      that reduction of photodetection noise by wavelet filtering significantly
      improves the accuracy of wavefront reconstruction from simulated and experimental
      data.

PMID- 20052303
TI  - Soft tissue small avascular tumor imaging with x-ray phase-contrast micro-CT in
      line holography.
AB  - To assess the feasibility of small soft tissue avascular tumor micro-CT imaging
      with x-ray phase-contrast in-line holography, we have studied micro-CT imaging
      with in-line geometry of small spheroidal avascular tumor models with quiescent
      cell core (< 250 mum) and various distributions of the proliferating cell density
      (PCD) forming the outer shell. We have simulated imaging with an ultrafast laser
      based x-ray source with a Mo target. We observe phase-contrast enhancement of the
      tumor boundaries in the reconstructed transaxial images, resulting in improved
      detection of small soft tissue tumors, providing that the PCD density gradient is
      sufficiently large.

PMID- 20052304
TI  - Is male circumcision as good as the HIV vaccine we've been waiting for?

PMID- 20052306
TI  - Magnetic Levitation of MC3T3 Osteoblast Cells as a Ground-Based Simulation of
      Microgravity.
AB  - Diamagnetic samples placed in a strong magnetic field and a magnetic field
      gradient experience a magnetic force. Stable magnetic levitation occurs when the
      magnetic force exactly counter balances the gravitational force. Under this
      condition, a diamagnetic sample is in a simulated microgravity environment. The
      purpose of this study is to explore if MC3T3-E1 osteoblastic cells can be grown
      in magnetically simulated hypo-g and hyper-g environments and determine if gene
      expression is differentially expressed under these conditions. The murine
      calvarial osteoblastic cell line, MC3T3-E1, grown on Cytodex-3 beads, were
      subjected to a net gravitational force of 0, 1 and 2 g in a 17 T superconducting
      magnet for 2 days. Microarray analysis of these cells indicated that
      gravitational stress leads to up and down regulation of hundreds of genes. The
      methodology of sustaining long-term magnetic levitation of biological systems are
      discussed.

PMID- 20052305
TI  - The mammalian phenotype ontology: enabling robust annotation and comparative
      analysis.
AB  - The mouse has long been an important model for the study of human genetic
      disease. Through the application of genetic engineering and mutagenesis
      techniques, the number of unique mutant mouse models and the amount of phenotypic
      data describing them are growing exponentially. Describing phenotypes of mutant
      mice in a computationally useful manner that will facilitate data mining is a
      major challenge for bioinformatics. Here we describe a tool, the Mammalian
      Phenotype Ontology (MP), for classifying and organizing phenotypic information
      related to the mouse and other mammalian species. The MP Ontology has been
      applied to mouse phenotype descriptions in the Mouse Genome Informatics Database
      (MGI, http://www.informatics.jax.org/), the Rat Genome Database (RGD,
      http://rgd.mcw.edu), the Online Mendelian Inheritance in Animals (OMIA,
      http://omia.angis.org.au/) and elsewhere. Use of this ontology allows comparisons
      of data from diverse sources, can facilitate comparisons across mammalian
      species, assists in identifying appropriate experimental disease models, and aids
      in the discovery of candidate disease genes and molecular signaling pathways.

PMID- 20052307
TI  - Pretreatment Intervention Increases Treatment Outcomes for Patients with Anxiety
      Disorders.
AB  - The current study evaluated the utility of a pretreatment intervention aimed at
      increasing treatment attendance. We extended past work by evaluating whether this
      intervention was associated with less impairment at termination. Given that
      patients with anxiety disorders demonstrate high rates of premature termination,
      we assessed whether these patients would be particularly likely to benefit. The
      sample included 172 patients at a community outpatient mental health clinic.
      Patients were assigned to the intervention condition (asked to imagine attending
      therapy sessions) or an information control condition. Number of sessions
      attended and termination Clinician Global Impressions (CGI) served as outcome
      variables. Contrary to prior work, the two conditions did not significantly
      differ on outcomes. Yet, patients with anxiety disorders in the intervention
      condition attended the most sessions and had least termination symptom severity.
      This intervention may provide a simple yet powerful method to increase treatment
      adherence and effectiveness for patients with anxiety disorders.

PMID- 20052308
TI  - Segmentation of Left Ventricle From 3D Cardiac MR Image Sequences Using A Subject
      Specific Dynamical Model.
AB  - Statistical model-based segmentation of the left ventricle from cardiac images
      has received considerable attention in recent years. While a variety of
      statistical models have been shown to improve segmentation results, most of them
      are either static models (SM) which neglect the temporal coherence of a cardiac
      sequence or generic dynamical models (GDM) which neglect the inter-subject
      variability of cardiac shapes and deformations. In this paper, we use a subject
      specific dynamical model (SSDM) that handles inter-subject variability and
      temporal dynamics (intra-subject variability) simultaneously. It can
      progressively identify the specific motion patterns of a new cardiac sequence
      based on the segmentations observed in the past frames. We formulate the
      integration of the SSDM into the segmentation process in a recursive Bayesian
      framework in order to segment each frame based on the intensity information from
      the current frame and the prediction from the past frames. We perform "Leave-one
      out" test on 32 sequences to validate our approach. Quantitative analysis of
      experimental results shows that the segmentation with the SSDM outperforms those
      with the SM and GDM by having better global and local consistencies with the
      manual segmentation.

PMID- 20052309
TI  - ESTIMATING A DOSE-RESPONSE RELATIONSHIP BETWEEN LENGTH OF STAY AND FUTURE
      RECIDIVISM IN SERIOUS JUVENILE OFFENDERS.
AB  - The effect of sanctions on subsequent criminal activity is of central theoretical
      importance in criminology. A key question for juvenile justice policy is the
      degree to which serious juvenile offenders respond to sanctions and/or treatment
      administered by the juvenile court. The policy question germane to this debate is
      finding the level of confinement within the juvenile justice system that
      maximizes the public safety and therapeutic benefits of institutional
      confinement. Unfortunately, research on this issue has been limited with regard
      to serious juvenile offenders. We use longitudinal data from a large sample of
      serious juvenile offenders from two large cities to 1) estimate a causal
      treatment effect of institutional placement, as opposed to probation, on future
      rate of rearrest and 2) investigate the existence of a marginal effect (i.e.,
      benefit) for longer length of stay once the institutional placement decision had
      been made. We accomplish the latter by determining a dose-response relationship
      between the length of stay and future rates of rearrest and self-reported
      offending. The results suggest that an overall null effect of placement exists on
      future rates of rearrest or self-reported offending for serious juvenile
      offenders. We also find that, for the group placed out of the community, it is
      apparent that little or no marginal benefit exists for longer lengths of stay.
      Theoretical, empirical, and policy issues are outlined.

PMID- 20052310
TI  - Modeling Informatively Missing Genotypes in Haplotype Analysis.
AB  - It is common to have missing genotypes in practical genetic studies. The majority
      of the existing statistical methods, including those on haplotype analysis,
      assume that genotypes are missing at random-that is, at a given marker, different
      genotypes and different alleles are missing with the same probability. In our
      previous work, we have demonstrated that the violation of this assumption may
      lead to serious bias in haplotype frequency estimates and haplotype association
      analysis. We have proposed a general missing data model to simultaneously
      characterize missing data patterns across a set of two or more biallelic markers.
      We have proved that haplotype frequencies and missing data probabilities are
      identifiable if and only if there is linkage disequilibrium between these markers
      under the general missing data model. In this study, we extend our work to multi
      allelic markers and observe a similar finding. Simulation studies on the analysis
      of haplotypes consisting of two markers illustrate that our proposed model can
      reduce the bias for haplotype frequency estimates due to incorrect assumptions on
      the missing data mechanism. Finally, we illustrate the utilities of our method
      through its application to a real data set from a study of scleroderma.

PMID- 20052311
TI  - Emotion Focused Therapy-Therapist Fidelity Scale (EFT-TFS): Conceptual
      Development and Content Validity.
AB  - The Emotion Focused Therapy-Therapist Fidelity Scale (EFT-TFS) is introduced as a
      scale to measure a therapist's fidelity to the EFT model. The rationale and
      conceptual development of the scale are presented. Members of an EFT electronic
      mailing list who participated in a survey (n=130) rated all of the items as
      highly important for the practice providing support for the content validity of
      the scale. Finally, the 13 items of the EFT-TFS are presented. Future research
      directions for the EFT-TFS are presented.

PMID- 20052312
TI  - A passive dual-circulator based transmit/receive switch for use with reflection
      resonators in pulse EPR.
AB  - In order to protect the low noise amplifier (LNA) in the receive arm of a pulsed
      250 MHz EPR bridge, it is necessary to install as much isolation as possible
      between the power exciting the spin system and the LNA when high power is present
      in the receive arm of the bridge, while allowing the voltage induced by the
      magnetization in the spin sample to be passed undistorted and undiminished to the
      LNA once power is reduced below the level that can cause a LNA damage. We discuss
      a combination of techniques to accomplish this involving the power-routing
      circulator in the bridge, a second circulator acting as an isolator with passive
      shunt PIN diodes immediately following the second circulator. The low resistance
      of the forward biased PIN diode passively generates an impedance mismatch at the
      second circulator output port during the high power excitation pulse and
      resonator ring down. The mismatch reflects the high power to the remaining port
      of the second circulator, dumping it into a system impedance matched load. Only
      when the power diminishes below the diode conduction threshold will the
      resistance of the PIN diode rise to a value much higher than the system
      impedance. This brings the device into conduction mode. We find that the present
      design passively limits the output power to 14 dBm independent of the input
      power. For high input power levels the isolation may exceed 60 dB. This level of
      isolation is sufficient to fully protect the LNA of pulse EPR bridge.

PMID- 20052313
TI  - Picogram material dosing of microstructures.
AB  - A solution delivery platform comprised of a suspended microcapillary connected to
      a microwell enables picogram solute deposition on suspended structures. Precision
      material placement in the capillary from a 100 pl drop inkjetted into the well is
      achieved without the destruction of the microstructure and adjacent submicron
      electrostatic gaps. This method scales to smaller structures without the need for
      drop miniaturization. The theory behind the solute transfer in the system is
      developed. Three regions in the drying process are observed and match with the
      model. The "accumulation" region builds solute concentration in the capillary.
      The "solidification" region initiates the solidification of solute starting at
      the free end of the capillary. The "termination" region is characterized by a
      rapid increase in the solidification due to an increase in the well concentration
      near the end of the drop lifetime. The accumulation time and solidification rate
      dependence on concentration compare well with the model.

PMID- 20052314
TI  - High-speed tuning of visible laser wavelength using a nanoimprinted grating
      optical tunable filter.
AB  - We report on a microelectromechanical tunable optical filter incorporating strain
      tunable nanoimprinted elastomeric grating with a pitch varied by 18%. This device
      enables tuning of optical fiber-guided laser wavelength between lambda=473 and
      532 nm within 0.5 ms by mechanically modulating the pitch with a silicon
      microactuator. We also demonstrate the use of the device for obtaining two-color
      images of livedead-stained cells with the color intensity ratio varied by the
      actuator voltage applied. The small structure of the device integrated on a
      silicon chip may be used in portable systems for optical switching and
      spectroscopy.

PMID- 20052315
TI  - Climate change could threaten blood supply by altering the distribution of vector
      borne disease: an Australian case-study.
AB  - BACKGROUND: Climate change is expected to promote more intense and prolonged
      outbreaks of vector-borne disease, and alter the geographic boundaries of
      transmission. This has implications for the safety and supply of fresh blood
      products around the world. In Australia, a recent outbreak of dengue fever caused
      a prolonged regional shortage in the supply of fresh blood products. OBJECTIVE:
      To highlight the potential for climate change to affect the safety and supply of
      blood globally through its impact on vector-borne disease, using the example of
      dengue in Australia as a case-study. DESIGN: We modelled geographic regions in
      Australia suitable for dengue transmission over the coming century under four
      climate change scenarios, estimated changes to the population at risk and effect
      on blood supply. RESULTS: Geographic regions with climates that are favourable to
      dengue transmission could expand to include large population centres in a number
      of currently dengue-free regions in Australia and reduce blood supply across
      several states. CONCLUSION: Unless there is strong intergovernmental action on
      greenhouse gas reduction, there could be an eight-fold increase in the number of
      people living in dengue prone regions in Australia by the end of the century.
      Similar impacts will be experienced elsewhere and for other vector-borne
      diseases, with regions currently on the margins of transmission zones most
      affected. Globally, climate change is likely to compound existing problems of
      blood safety and supply in already endemic areas and cause future shortages in
      fresh blood products through its impact on transmission of vector-borne disease.

PMID- 20052316
TI  - Consumer health informatics: is there a role for HIM professionals?

PMID- 20052317
TI  - Expanding the health information management public health role.

PMID- 20052318
TI  - Redefining HIM leadership: toward an HIM leadership framework: a commentary on
      HIM leadership.

PMID- 20052319
TI  - Redefining the health information management privacy and security role.

PMID- 20052320
TI  - Redefining the health information management scholar role.

PMID- 20052321
TI  - Redefining the roles of health information management professionals in health
      information technology.

PMID- 20052322
TI  - Research and policy model for health informatics and information management.

PMID- 20052324
TI  - The progression of the roles and functions of HIM professionals: a look into the
      past, present, and future.

PMID- 20052325
TI  - The role of HIM professionals in quality management.
AB  - HIM professionals have always been actively involved in various aspects of
      healthcare quality management. In the decade since publication of To Err Is
      Human, the scope and volume of quality management activities have accelerated.
      Having quality at the forefront of the national agenda has inevitably created
      employment opportunities as well as expansion of professional responsibilities.
      This article describes the contemporary quality-related functions of HIM
      professionals and the core competencies necessary to support these functions.

PMID- 20052326
TI  - The death of children: Our failures and possibilities.

PMID- 20052327
TI  - Current management of Herpes simplex infection in pregnant women and their
      newborn infants: What's hot and what's not.

PMID- 20052328
TI  - A rational approach to the child with mental retardation for the paediatrician.
AB  - Mental Retardation (MR) is a problem encountered in almost all paediatric
      clinical settings. The assessment of a child with MR is a common diagnostic and
      management dilemma for paediatricians. The field of MR research is currently in a
      state of flux regarding not just our understanding of the condition, but also in
      the language and the processes we use in naming, defining and describing MR. This
      article will provide a better understanding and a rational approach toward MR.
      Prevalence rates for MR are variable in the literature and may be attributable to
      the variation in major classification systems and the diversity in study
      operation definitions and methodologies. Etiologies of MR are diverse and include
      many different influences. MR most often presents during infancy or preschool
      years as developmental delay. There is no universally accepted approach to the
      etiological work-up of mental retardation. The number of medical conditions
      associated with MR that are completely treatable by medical means remains small.
      The paediatrician plays a key role establishing short and long term treatment
      goals, as well as providing support to families who have children with MR.

PMID- 20052330
TI  - Death of a child: Parental perception of grief intensity - End-of-life and
      bereavement care.
AB  - OBJECTIVE: The death of a child is a tragedy resulting in family trauma and
      disorganization. The present study sought to evaluate the intensity of grief
      experienced by parents who have lost a child in the perinatal period (stillbirth,
      premature baby, term baby less than one month) and parents who have lost a child
      after the perinatal period (one month to 18 years). METHOD: To compare the
      intensities of the bereavement reactions among grieving parents and to follow the
      course of such phenomena, a detailed bereavement questionnaire (the French
      version of the Texas Revised Inventory of Grief [TRIG-F]) was used. The TRIG-F is
      a three-part questionnaire that quantifies the intensity of grief near the time
      of death and in the present, and the perceived capacity of coping. RESULTS:
      Seventy-one bereaved parents, representing 43 families, completed the
      questionnaire. Parents who lost a child after the perinatal period showed grief
      at a higher intensity, measured by the TRIG-F, than parents who had lost a child
      in the perinatal period (83+/-22 versus 69+/-20 [mean+/-SD]; P=0.004). Mothers
      expressed a greater intensity of grief than fathers. No significant difference
      between mothers of the perinatal group and mothers of the postperinatal group was
      shown. Sudden death and death ocurring at home were associated with a higher
      grief intensity. CONCLUSION: Bereavement after the loss of a newborn or an older
      child is intense and prolonged. These findings support the importance of
      bereavement care for grieving parents and suggest that these parents appreciate
      help from health care professionals.

PMID- 20052329
TI  - Death and bereavement in a paediatric intensive care unit: Parental perceptions
      of staff support.
AB  - OBJECTIVES: To determine which staff behaviours and interventions were helpful to
      a family who had a child die in the intensive care unit (ICU) and which
      behaviours could be improved. METHODS: Families whose child died six to 18 months
      earlier were invited to participate. Families whose child's death involved a
      coroner's inquiry were excluded. Family members were interviewed by a grief
      counselor, and completed the Grief Experience Inventory Profile and an
      empirically designed questionnaire. RESULTS: No family refused to participate.
      All family members (13 families, 24 individuals) reported that they wanted, were
      offered and had: time to be alone with their child, time to hold the child,
      chances to discuss their feelings, and an opportunity to cry and express their
      emotions openly. Tangible mementos of the child were appreciated. Support
      provided by nursing staff was rated as excellent. Some physicians appeared to be
      abrupt, cold and unfeeling. Hospital social workers and chaplains, when
      available, were appreciated. Parents valued access to private space and holding
      their child, but these options needed to be suggested, as they did not know to
      ask for them. Some families wanted more information about funeral arrangements;
      most wanted more timely information about autopsy results and feedback on organ
      donations. Follow-up contact from the hospital about four weeks after the death
      was valued. Families saw the study as an opportunity to provide feedback that may
      help others. CONCLUSIONS: Many acute bereavement interventions need to be
      initiated by staff because families do not know to request them. Physicians do
      not always meet individual family's needs for support. Contact initiated by staff
      following a death is appreciated.

PMID- 20052331
TI  - Case 1: A toddler with recurrent chest problems.

PMID- 20052332
TI  - Case 2: Edematous toddler with acute abdominal pain.

PMID- 20052334
TI  - Lap-belt injuries: A view from the bedside.

PMID- 20052333
TI  - [Not Available].

PMID- 20052336
TI  - Acellular pertussis vaccine for adolescents.

PMID- 20052335
TI  - Acellular pertussis vaccine for adolescents.

PMID- 20052337
TI  - Varicella vaccine for children.

PMID- 20052340
TI  - Clinical features, risk factors and outcomes of bacteremia due to enterococci
      with high-level gentamicin resistance: comparison with bacteremia due to
      enterococci without high-level gentamicin resistance.
AB  - High-level gentamicin resistance (HLGR) in enterococci has increased since the
      1980s, but the clinical significance of the resistance and its impact on outcome
      have not been established. One hundred and thirty-six patients with bacteremia
      caused by enterococci with HLGR (HLGR group) were compared with 79 patients with
      bacteremia caused by enterococci without HLGR (non-HLGR group). Hematologic
      malignancy, neutropenia, Enterococcus faecium infection, nosocomial infection and
      monomicrobial bacteremia were more common in the HLGR group than the non-HLGR
      group, and APACHE II scores were also higher (P<0.05, in each case). Neutropenia,
      monomicrobial infection, stay in intensive care at culture, and use of 3rd
      generation cephalosporin, were independent risk factors for acquisition of HLGR
      enterococcal bacteremia. Fourteen-day and 30-day mortalities were higher in the
      HLGR group than the non-HLGR group in univariate analysis (37% vs. 15%, P=0.001;
      50% vs. 22%, P<0.001). However, HLGR was not an independent risk factor for
      mortality due to enterococcal bacteremia in multivariate analysis. Therefore,
      HLGR enterococcal bacteremia is associated with more severe comorbid conditions
      and higher mortality than non-HLGR enterococcal bacteremia but the HLGR itself
      does not contribute significantly to mortality.

PMID- 20052341
TI  - Idarubicin plus behenoyl cytarabine and 6-thioguanine compares favorably with
      idarubicin plus cytarabine-based regimen for children with previously untreated
      acute myeloid leukemia: 10-year retrospective, multicenter study in Korea.
AB  - We investigated the outcome of idarubicin plus N(4)-behenoyl-1-beta-D
      arabinofuranosyl cytosine (BHAC)-based chemotherapy (BHAC group, n=149) compared
      to idarubicin plus cytarabine-based chemotherapy (cytarabine group, n=191) for
      childhood acute myeloid leukemia (AML). Between January 1996 and December 2005,
      340 children with AML from 5 university hospitals in Korea received the BHAC
      based or cytarabine-based chemotherapy, with or without hematopoietic stem cell
      transplantation. After induction therapy, 264 (77.6%) of 340 children achieved a
      complete remission (CR) and 43 (12%) achieved a partial remission (PR). The CR
      rate in the BHAC group was higher than in the cytarabine group (85.2% vs. 71.7%,
      P=0.004). However, the overall response rate (CR+PR) was not different between
      the two groups (93.3% vs. 87.9%, P=0.139). The 5-yr estimates of overall survival
      (OS) of children in the two groups were similar (54.9% for the BHAC group vs.
      52.4% for the cytarabine group, P=0.281). Although the results were analyzed
      according to the treatment type and cytogenetic risk, the OS showed no
      significant difference between the BHAC group and the cytarabine group. In the
      present study, the clinical outcomes of the BHAC-based chemotherapy, consisting
      of BHAC, idarubicin, and 6-TG, are comparable to that of the cytarabine-based
      chemotherapy for childhood AML.

PMID- 20052343
TI  - Patent ductus arteriosus closure in prematurities weighing less than 1 kg by
      subaxillary mini-thoracotomy.
AB  - The surgical closure of patent ductus arteriosus (PDA) is provided more
      frequently in extremely low birth weight babies who are usually deemed unsuitable
      for pharmacological closure. We have adopted subaxillary mini-thoracotomy in
      order to lessen surgical trauma in these babies; and its clinical results were
      analyzed. From April 2004 to August 2008, out of 50 babies at the neonatal
      intensive care unit who underwent the surgical closure of PDA, 22 premature
      babies weighing less than 1 kg at operation were included in the study. Eleven
      babies were males and mean gestational age was 27 weeks ranging from 23(+3) to
      30(+2) weeks. Mean body weight at operation was 816 g ranging from 490 to 989 g
      and average age at operation was 17.9+/-11.9 days. Of them, 17 babies (72%) were
      ventilator dependent preoperatively, as compared with 13 out of 28 (46%) babies
      that weighed more than 1 kg (P<0.05). Four babies did not survive to discharge.
      Among 28 babies who were heavier than 1 kg, there were only one death. However,
      the mortality difference was not statistically significant (P=0.11). All
      mortalities were caused by inherent problems of prematurity and co-morbidities.
      Out of 17 babies who had been ventilator dependent preoperatively, 13 weaned off
      successfully at 17.0+/-23.9 days after the operation. The baby patients heavier
      than 1 kg weaned at 6.0+/-5.3 days (P=0.27). Surgical outcome of simple and less
      invasive subaxillary mini-thoracotomy was satisfactory; the surgery is highly
      recommended for ductal closure in extremely low weight premature babies.

PMID- 20052342
TI  - HMG-CoA reductase inhibitor improves endothelial dysfunction in spontaneous
      hypertensive rats via down-regulation of caveolin-1 and activation of endothelial
      nitric oxide synthase.
AB  - Hypertension is associated with endothelial dysfunction and increased
      cardiovascular risk. Caveolin-1 regulates nitric oxide (NO) signaling by
      modulating endothelial nitric oxide synthase (eNOS). The purpose of this study
      was to examine whether HMG-CoA reductase inhibitor improves impaired endothelial
      function of the aorta in spontaneous hypertensive rat (SHR) and to determine the
      underlying mechanisms involved. Eight-week-old male SHR were assigned to either a
      control group (CON, n=11) or a rosuvastatin group (ROS, n=12), rosuvastatin (10
      mg/kg/day) administered for eight weeks. Abdominal aortic rings were prepared and
      responses to acetylcholine (10(-9)-10(-4) M) were determined in vitro. To
      evaluate the potential role of NO and caveolin-1, we examined the plasma activity
      of NOx, eNOS, phosphorylated-eNOS and expression of caveolin-1. The relaxation in
      response to acetylcholine was significantly enhanced in ROS compared to CON.
      Expression of eNOS RNA was unchanged, whereas NOx level and phosphorylated-eNOS
      at serine-1177 was increased accompanied with depressed level of caveolin-1 in
      ROS. We conclude that 3-Hydroxy-3-methylglutaryl Coenzyme-A (HMG-CoA) reductase
      inhibitor can improve impaired endothelial dysfunction in SHR, and its underlying
      mechanisms are associated with increased NO production. Furthermore, HMG-CoA
      reductase inhibitor can activate the eNOS by phosphorylation related to decreased
      caveolin-1 abundance. These results imply the therapeutic strategies for the high
      blood pressure-associated endothelial dysfunction through modifying caveolin
      status.

PMID- 20052344
TI  - Venous thromboembolism in Korean patients undergoing major orthopedic surgery: a
      prospective observational study using computed tomographic (CT) pulmonary
      angiography and indirect CT venography.
AB  - In patients undergoing major orthopedic surgery, data of deep venous thrombosis
      (DVT) and pulmonary embolism (PE) are lacking as studied by computed tomographic
      (CT) pulmonary angiography and indirect CT venography (CTPA-CTV). A prospective
      observational study was performed for 363 Korean patients undergoing major
      orthopedic surgery to determine the incidence of venous thromboembolism (VTE),
      especially proximal DVT and PE. The incidence of VTE was 16.3% (n=59). Of them, 8
      patients (2.2%) were symptomatic. The rate of VTE was the highest in patients who
      underwent total knee replacement (40.4%), followed by hip fracture surgery
      (16.4%), and total hip replacement (8.7%; P<0.001). The incidence of PE was 6.6%
      (n=24). Of them, 4 patients (1.1%) were symptomatic. Forty-one patients (11.3%)
      were in the proximal DVT or PE group. Based on multivariate analysis, total knee
      replacement and age > or =65 yr were significant risk factors for proximal DVT or
      PE in patients undergoing major orthopedic surgery (odds ratio [OR], 2.4; 95%
      confidence interval [CI], 1.1-5.1; P=0.025; and OR, 2.1; 95% CI, 1.0-4.4;
      P=0.046, respectively). Taken together, the overall incidence of PE was 6.6% and
      rate of symptomatic PE rate was 1.1%. Knee joint replacement and age > or =65 yr
      were significant risk factors for proximal DVT or PE.

PMID- 20052345
TI  - PPARgamma agonist and angiotensin II receptor antagonist ameliorate renal
      tubulointerstitial fibrosis.
AB  - The peroxisome proliferator activated receptor (PPAR)gamma agonist is used as
      antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions.
      Beyond these actions, antifibrotic effects have been reported. We examined
      antifibrotic effects of PPARgamma agonist and interaction with angiotensin
      receptor antagonist in the unilateral ureteral obstruction (UUO) model. After
      UUO, mice were divided to four groups: no treatment (CONT), pioglitazone
      treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14,
      CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis.
      The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their
      expressions were increased in CONT group and decreased in the all treated groups
      compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among
      treated groups, was decreased compared to CONT group. The expression of TGF-beta1
      from real time RT PCR showed markedly increased in the CONT group and decreased
      in all treated groups compared to CONT. These data suggest the pioglitazone
      inhibited tubulointerstitial fibrosis, however, the synergism between
      pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1
      and TGF-beta/Smad2 in the treated groups, PAI-1 and TGF-beta are likely linked to
      the decreased renal tubulointerstitial fibrosis. According to these results, the
      PPARgamma agonist might be used in the treatment of renal fibrotic disease.

PMID- 20052346
TI  - Serum cystatin C is a potential endogenous marker for the estimation of renal
      function in male gout patients with renal impairment.
AB  - Serum creatinine level is the most commonly used indices for assessment of
      glomerular filtration rate (GFR), even though these indices have been shown to
      have some limitations in clinical practice. We investigated the diagnostic
      efficacy of serum cystatin C compared to that of serum creatinine levels and
      identified the relating factors associated with changes in serum cystatin C
      levels in gout patients with renal impairment. A total of 68 gouty patients with
      renal impairment were enrolled in this study. Diagnostic efficacy of serum
      cystatin C levels was evaluated through non-parametric receiver operating
      characteristic (ROC) analysis. The risk factors for changes in serum cystatin C
      levels were confirmed using multivariate regression analysis. With 24-hr urine
      creatinine clearance (Ccr) as the reference for GFR, 1/cystatin C (r=0.702,
      P<0.001) showed a significantly higher correlation with Ccr than 1/creatinine
      (r=0.665, P<0.001). Multivariate correlation analysis demonstrated that the
      clinical parameters for increased serum cystatin C are a higher stage of chronic
      kidney disease, older age, use of allopurinol, and lower high density lipoprotein
      cholesterol. The area under the curve (AUC) at ROC plots identified that of serum
      cystatin C was significantly greater than that of serum creatinine (AUC 0.804 of
      cystatin C and AUC 0.745 of creatinine). The study suggests that serum cystatin C
      is a reliable endogenous marker for the assessment of renal function or GFR in
      gout patients with renal impairment.

PMID- 20052347
TI  - Difference of body compositional changes according to the presence of weight
      cycling in a community-based weight control program.
AB  - Many obese people who try to control body weight experience weight cycling (WC).
      The present study evaluated the importance of WC in a community-based obesity
      intervention program. We analyzed the data of 109 Korean participants (86% women)
      among 177 subjects who had completed a 12-week intervention program at two public
      health centers in Korea from April to December, 2007. Completion of a self
      administrated questionnaire at baseline was used to obtain anthropometric
      measurements, and laboratory testing was done before and after the program.
      Differences in body composition change and obesity-related life style between the
      two groups were compared with respect to WC and non-weight cycling (NWC). After
      12 weeks, both groups showed reductions in weight, waist circumference, and body
      mass index. The group differences were not significant. However, significant
      differences were evident for the WC group compared to the NWC group in fat
      percent mass (WC vs. NWC, -3.49+/-2.31% vs. -4.65+/-2.59%, P=0.01), fat free mass
      (WC vs. NWC, -0.95+/-1.37 kg vs. -0.38+/-1.05 kg, P=0.01), and total cholesterol
      (WC vs. NWC, -3.32+/-14.63 vs. -16.54+/-32.39, P=0.005). In conducting a
      community-based weight control program that predominantly targets women, changes
      of body composition and total cholesterol may be less effective in weight cyclers
      than in non-weight cyclers.

PMID- 20052348
TI  - Long-term treatment outcomes for autoimmune hepatitis in Korea.
AB  - Immunosuppressive therapy can improve clinical, biochemical and histological
      features and considerably prolong survival in patients with autoimmune hepatitis.
      Although ethnicity may affect disease severity and presentation, the long-term
      outcome of immunosuppression in Korean populations is unknown. This study was
      aimed to assess the efficacy of immunosuppressive therapy and determine the
      prognosis of autoimmune hepatitis in Korean populations. We reviewed the medical
      records of 86 patients diagnosed as having autoimmune hepatitis at the Samsung
      Medical Center between 1994 and 2008. Seventy-two (83.7%) patients reached
      remission after a median treatment duration of 3.5 months (range 1 to 44 months).
      Attempts to withdraw medications were made in 24 cases after the median treatment
      duration of 36 months (median 6 to 125 months). Thirteen of 24 (54.1%) patients
      relapsed after treatment withdrawal. Of the 86 patients, 6 (7.2%) experienced
      disease progression and the overall 5-and 10-yr progression-free survival rates
      were 91.2% and 85.5%, respectively. In conclusion, immunosuppressive therapy for
      autoimmune hepatitis results in a favorable rate of remission and excellent
      progression-free survival, but the relapse rate after treatment withdrawal is
      high. This suggests that long-term immunosuppressive therapy may be particularly
      important for treatment of Korean patients.

PMID- 20052349
TI  - Examination of geographical, clinical and intrahost variations in the 3' repeat
      region of cagA gene in Helicobacter pylori.
AB  - The size variation of the cytoxin-associated protein (cagA), which is dependent
      on the 3' repeat region (3'RR) of the cagA gene, is known to play a crucial role
      in the pathogenesis of Helicobacter pylori infection. The present study evaluated
      the relationship between the 3'RR variation and the geographic distribution,
      clinical manifestations, and locations of colonization in the stomach. We
      evaluated the 3'RR of H. pylori isolates from 78 patients with gastric cancer,
      peptic ulcer, and non-ulcer dyspepsia from Japan, Hong Kong, India, and the
      United States and assessed the variations of 3'RR according to the geographical
      and clinical characteristics. Sixty eight (87.2%) patients had the same 650 bp
      band without geographical differences. The frequency of polymorphisms in the 3'RR
      did not differ when compared to the clinical manifestations (P=0.868). The length
      of 3'RR did not differ by location of colonization. In conclusion, the 3'RR
      variation of cagA gene is not associated with the geographical and clinical
      characteristics of the patients studied.

PMID- 20052350
TI  - Usefulness of non-invasive markers for predicting significant fibrosis in
      patients with chronic liver disease.
AB  - The purpose of this prospective study was to verify and compare the strengths of
      various blood markers and fibrosis models in predicting significant liver
      fibrosis. One hundred fifty-eight patients with chronic liver disease who
      underwent liver biopsy were enrolled. The mean age was 41 yr and male patients
      accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%)
      and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were
      assessed according to the Batts and Ludwig scoring system. Significant fibrosis
      was defined as > or =F2. Sixteen blood markers were measured along with liver
      biopsy, and estimates of hepatic fibrosis were calculated using various
      predictive models. Predictive accuracy was evaluated with a receiver-operating
      characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106
      cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid,
      and haptoglobin were found to be independently related to significant hepatic
      fibrosis. A new predictive model was constructed based on these variables, and
      its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In
      conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are
      independent predictors for significant hepatic fibrosis in chronic liver disease.

PMID- 20052351
TI  - Prevalence of metabolic syndrome and obesity in adolescents aged 12 to 19 years:
      comparison between the United States and Korea.
AB  - This study compared the prevalence of metabolic syndrome (MetS), its risk
      factors, and obesity in adolescents in the United States (US) and Korea. Data
      were obtained from 2003-2004 US National Health and Nutrition Examination Survey
      (NHANES) and 2005 Korea NHANES for adolescents aged 12-19 yr in the US (n=734)
      and in Korea (n=664). The 2007 International Diabetes Federation (IDF) pediatric
      definition for diagnosis of MetS and the 2000 US Growth Charts and 2007 Korea
      Growth Charts for assessment of obesity were utilized. The prevalence of
      metabolic syndrome in US and Koreans was 5.5% and 2.5%, respectively. The
      prevalence of obesity was 18.1% in US compared to 9.0% in Koreans. The prevalence
      of abdominal obesity, hyperglycemia, and hypertriglyceridemia were higher in the
      US, whereas that of low HDL-C levels was higher in Korea. Despite the doubled
      prevalence for the single entities of MetS and obesity in the US, the prevalence
      of MetS in obese US and Koreans did not differ (20.8% and 24.3%, respectively).
      In conclusion, there are differences in the prevalence of MetS, obesity, and the
      individual MetS risk factors between the US and Korean adolescents; however, the
      risk of MetS among obese adolescents is similar in both countries.

PMID- 20052352
TI  - Nutritional status of vitamin D and the effect of vitamin D supplementation in
      Korean breast-fed infants.
AB  - We investigated the vitamin D status and the effect of vitamin D supplementation
      in Korean breast-fed infants. The healthy term newborns were divided into 3
      groups; A, formula-fed; B, breast-fed only; S, breast-fed with vitamin D
      supplementation. We measured serum concentrations of vitamin D (25OHD3), calcium
      (Ca), phosphorus (P), alkaline phosphatase (AP), intact parathyroid hormone
      (iPTH) and bone mineral density (BMD) at 6 and 12 months of age. Using
      questionnaires, average duration of sun-light exposure and dietary intake of
      vitamin D, Ca and P were obtained. At 6 and 12 months of age, 25OHD3 was
      significantly higher in group S than in group B (P<0.001). iPTH was significantly
      lower in group S than in group B at 6 months (P=0.001), but did not differ at 12
      months. Regardless of vitamin D supplementation, BMD was lower in group B and S
      than in group A (P<0.05). Total intake of vitamin D differed among 3 groups
      (P<0.001, A>S>B), but total intake of Ca and P were higher in group A than in
      group B and S (P<0.001). In conclusion, breast-fed infants show lower vitamin D
      status and bone mineralization than formula-fed infants. Vitamin D
      supplementation (200 IU/day) in breast-fed infants increases serum 25-OH vitamin
      D(3), but not bone mineral density.

PMID- 20052353
TI  - Immunogenicity of Haemophilus influenzae type b conjugate vaccines in Korean
      infants: a meta-analysis.
AB  - A meta-analysis was performed on the immunogenicity of Haemophilus influenzae
      type b (Hib) conjugate vaccines after 2 (2 and 4 months) and 3 doses (2, 4, and 6
      months) in Korean infants. A database search of MEDLINE, KoreaMed, and Korean
      Medical Database was done. The primary outcome measure was the proportion of
      infants with anti-polyribosylribitol phosphate (PRP) concentrations > or =1.0
      microg/mL. Eight studies including eleven trials were retrieved. One trial
      reported on the diphtheria toxoid conjugate vaccine (PRP-D) and 2 trials each on
      the mutant diphtheria toxin (PRP-CRM) and Neisseria meningitidis outer-membrane
      protein (PRP-OMP) conjugate vaccine. Heterogeneity in study designs between
      trials on PRP-CRM was noted and one trial reported on a monovalent and another on
      a combination PRP-OMP vaccine. Thus, a meta-analysis was conducted only on the
      tetanus toxoid conjugate vaccine (PRP-T). After a primary series of 2 doses and 3
      doses, 80.6% (95% confidence interval [CI]; 76.0-85.1%) and 95.7% (95% CI; 94.0
      98.0%) of infants achieved an antibody level > or =1.0 microg/mL, respectively.
      The immunogenic response to the PRP-T vaccine was acceptable after a primary
      series of 3 doses and also 2 doses. A reduced number of doses as a primary series
      could be carefully considered in Korean infants.

PMID- 20052354
TI  - Clinical efficacy of organ-preserving pancreatectomy for benign or low-grade
      malignant potential lesion.
AB  - The clinical usefulness of organ-preserving pancreatectomy is not well
      established due to technical difficulty and ambiguity of functional merit. The
      purpose of this study is to evaluate the clinical efficacy of organ-preserving
      pancreatectomy such as duodenum-preserving resection of the head of the pancreas
      (DPRHP), pancreatic head resection with segmental duodenectomy (PHRSD), central
      pancreatectomy (CP) and spleen-preserving distal pancreatectomy (SPDP). Between
      1995 and 2007, the DPRHP were performed in 14 patients, the PHRSD in 16 patients,
      the CP in 13 patients, and the SPDP in 45 patients for preoperatively diagnosed
      benign lesions or tumors with low-grade malignant potential. The clinical
      outcomes including surgical details, postoperative complications and long-term
      functional outcomes were compared between organ-preserving pancreatectomy and
      conventional pancreatectomy group. Major postoperative complications constituted
      the following: bile duct stricture (7.1% [1/14]) in DPRHP, delayed gastric
      emptying (31.2% [5/16]) in PHRSD, pancreatic fistula (21.4% [3/14]) in CP. There
      were no significant differences in postoperative complications and long-term
      functional outcomes between two groups. Organ-preserving pancreatectomy is
      associated with tolerable postoperative complications, and good long-term outcome
      comparing to conventional pancreatectomy. Organ-preserving pancreatectomy could
      be alternative treatment for benign or low-grade malignant potential lesion of
      the pancreas or ampullary/parapapillary duodenum.

PMID- 20052355
TI  - Surgical treatment of inferior vena cava tumor thrombus in patients with renal
      cell carcinoma.
AB  - Radical nephrectomy with inferior vena cava (IVC) thrombectomy remains the most
      effective therapeutic option in patients with renal cell carcinoma and IVC tumor
      thrombus. Cephalic extension of the thrombus is closely related to perioperative
      morbidity. We purposed to design a safe and successful surgical strategy through
      a review of our surgical experience and treatment results in 35 patients
      (male:female=28:7, mean age=56 yr [32-77]) who underwent IVC thrombectomy with
      radical nephrectomy between January 1997 and December 2006. The limit of tumor
      extension was level I in 10 patients (28.6%), level II in 17 (48.6%), and level
      III and IV in 4 patients each (11.4%). Liver mobilization with hepatic vascular
      exclusion was performed in 12 patients and cardiopulmonary bypass in 7. Thirty
      two primary closures, 2 patch closures, and 1 graft interposition were performed.
      One patient underwent simultaneous pulmonary embolectomy because of an operative
      pulmonary embolism. There was no operative mortality, and the overall survival at
      5-yr was 50.8%. Complete thrombus removal without tumor fragmentation under long
      venotomy on fully exposed involved IVC is recommended for successful result in a
      bloodless operative field. The applicability of liver mobilization, hepatic
      vascular exclusion, and cardiopulmonary bypass, can be determined by the level of
      thrombus.

PMID- 20052356
TI  - Efficacy and safety of tamsulosin for the treatment of non-neurogenic voiding
      dysfunction in females: a 8-week prospective study.
AB  - We evaluated the therapeutic effects of tamsulosin for women with non-neurogenic
      voiding dysfunction. Women who had voiding dysfunctions for at least 3 months
      were included. Inclusion criteria were age > or =18 yr, International Prostate
      Symptom Score (IPSS) of > or =15, and maximum flow rate (Q(max)) of > or =12
      mL/sec and/or postvoid residuals (PVR) of > or =150 mL. Patients with neurogenic
      voiding dysfunction or anatomical bladder outlet obstruction were excluded. All
      patients were classified according to the Blaivas-Groutz nomogram as having no or
      mild obstruction (group A) or moderate or severe obstruction (group B). After 8
      weeks of treatment, treatment outcomes and adverse effects were evaluated. One
      hundred and six patients were evaluable (70 in group A, 36 in group B). After
      treatments, mean IPSS, bother scores, Q(max), PVR, diurnal and nocturnal
      micturition frequencies and scored form of the Bristol Female Lower Urinary Tract
      Symptoms questionnaire (BFLUTS-SF) were changed significantly. Eighty-nine
      patients (84%) reported that the treatment was beneficial. The proportion of
      patients reported that their bladder symptoms caused "moderate to many severe
      problems" were significantly decreased. No significant difference were observed
      between the groups in terms of IPSS, bother score, Q(max), PVR, micturition
      frequency, and BFLUTS-SF changes. Adverse effects related to medication were
      dizziness (n=3), de novo stress urinary incontinence (SUI) (n=3), aggravation of
      underlying SUI (n=1), fatigue (n=1). Tamsulosin was found to be effective in
      female patients with voiding dysfunction regardless of obstruction grade.

PMID- 20052357
TI  - Severity of post-stroke aphasia according to aphasia type and lesion location in
      Koreans.
AB  - To determine the relations between post-stroke aphasia severity and aphasia type
      and lesion location, a retrospective review was undertaken using the medical
      records of 97 Korean patients, treated within 90 days of onset, for aphasia
      caused by unilateral left hemispheric stroke. Types of aphasia were classified
      according to the validated Korean version of the Western Aphasia Battery (K-WAB),
      and severities of aphasia were quantified using WAB Aphasia Quotients (AQ).
      Lesion locations were classified as cortical or subcortical, and were determined
      by magnetic resonance imaging. Two-step cluster analysis was performed using AQ
      values to classify aphasia severity by aphasia type and lesion location. Cluster
      analysis resulted in four severity clusters: 1) mild; anomic type, 2) moderate;
      Wernicke's, transcortical motor, transcortical sensory, conduction, and mixed
      transcortical types, 3) moderately severe; Broca's aphasia, and 4) severe; global
      aphasia, and also in three lesion location clusters: 1) mild; subcortical 2)
      moderate; cortical lesions involving Broca's and/or Wernicke's areas, and 3)
      severe; insular and cortical lesions not in Broca's or Wernicke's areas. These
      results revealed that within 3 months of stroke, global aphasia was the more
      severely affected type and cortical lesions were more likely to affect language
      function than subcortical lesions.

PMID- 20052358
TI  - The anti-inflammatory effects of ulinastatin in trauma patients with hemorrhagic
      shock.
AB  - We investigated the use of ulinastatin in association with the suppression of
      polymorphonuclear leukocyte elastase (PMNE), tumor necrosis factor alpha (TNF
      alpha) and interleukin 6 (IL-6), and its effects on the prognosis of patients
      with traumatic hemorrhagic shock. Nineteen patients who visited the emergency
      department for traumatic hemorrhagic shock were enrolled. Eleven patients were
      randomly selected to receive a total of 300,000 IU of ulinastatin. Measurements
      of serum PMNE, TNF-alpha and IL-6 were taken before ulinastatin treatment at 24
      hr, two days, three days, and seven days after admission. We compared the
      Systemic Inflammatory Response Syndrome scores, Multiple Organ Dysfunction
      Syndrome scores and Acute Physiology, age, Chronic Health Evaluation III scores
      of the control and ulinastatin groups. There were no significant differences in
      baseline values, laboratory data, treatment or mortality between the two groups.
      The serum PMNE levels in the ulinastatin group were lower than in the control
      group on the second hospitalized day. Serum TNF-alpha and IL-6 levels in the
      ulinastatin group decreased 24 hr after admission but had no significance. It is
      suggested that ulinastatin treatment could decrease the serum PMNE levels in
      trauma patients with hemorrhagic shock at 48 hr after treatment.

PMID- 20052359
TI  - A proposal of new reference system for the standard axial, sagittal, coronal
      planes of brain based on the serially-sectioned images.
AB  - Sectional anatomy of human brain is useful to examine the diseased brain as well
      as normal brain. However, intracerebral reference points for the axial, sagittal,
      and coronal planes of brain have not been standardized in anatomical sections or
      radiological images. We made 2,343 serially-sectioned images of a cadaver head
      with 0.1 mm intervals, 0.1 mm pixel size, and 48 bit color and obtained axial,
      sagittal, and coronal images based on the proposed reference system. This
      reference system consists of one principal reference point and two ancillary
      reference points. The two ancillary reference points are the anterior commissure
      and the posterior commissure. And the principal reference point is the midpoint
      of two ancillary reference points. It resides in the center of whole brain. From
      the principal reference point, Cartesian coordinate of x, y, z could be made to
      be the standard axial, sagittal, and coronal planes.

PMID- 20052360
TI  - Hybrid procedure for a traumatic aortic rupture consisting of endovascular repair
      and minimally invasive arch vessel transposition without sternotomy.
AB  - Emergency surgical repair for acute traumatic aortic ruptures has been associated
      with a high peri-procedural mortality rate. Endovascular stent-grafting, as a
      less invasive procedure, has shown encouraging results. This report describes a
      patient with a short landing zone, who was treated by transposing the supra
      aortic branch without sternotomy, followed by covered stent-grafting with an
      extended proximal bare portion to enhance fixation.

PMID- 20052361
TI  - Partial pericardial defect incidentally discovered during coronary bypass
      surgery.
AB  - A 71-yr-old male patient with three vessel coronary artery disease underwent a
      coronary artery bypass graft. The patient was found to have a large pericardial
      defect at the apex of the heart that measured approximately 18 cm in
      circumference. The edge of the pericardial defect impinged on the epicardial
      coronary arteries. The left phrenic nerve descended via the dorsal boundary of
      the pericardial defect. Following coronary artery bypass grafting, the
      pericardial defect was repaired with a polytetrafluorethylene patch. The patient
      had an uncomplicated postoperative course.

PMID- 20052362
TI  - A case of mexiletine-induced hypersensitivity syndrome presenting as eosinophilic
      pneumonia.
AB  - An 82-yr-old man was presented with fever and cough accompanied by generalized
      erythematous rash. He had taken mexiletine for 5 months, as he had been diagnosed
      with dilated cardiomyopathy and ventricular arrhythmia. Laboratory studies showed
      peripheral blood eosinophilia and elevated liver transaminase levels. Chest
      radiographs showed multiple nodular consolidations in both lungs. Biopsies of the
      lung and skin lesions revealed eosinophilic infiltration. After a thorough review
      of his medication history, mexiletine was suspected as the etiologic agent. After
      discontinuing the mexiletine and starting oral prednisolone, the patient
      improved, and the skin and lung lesions disappeared. Subsequently, mexiletine was
      confirmed as the causative agent based on a positive patch test. Drug-induced
      hypersensitivity syndrome is a severe adverse reaction to drugs and results from
      treatment with anticonvulsants, allopurinol, sulfonamides, and many other drugs.
      Several cases of mexiletine-induced hypersensitivity syndrome have been reported
      in older Japanese males with manifestation of fever, rash, peripheral blood
      eosinophilia, liver dysfunction without other organ involvement. Here, we report
      a case of mexiletine-induced hypersensitivity syndrome which presented as
      eosinophilic pneumonia in a Korean male.

PMID- 20052363
TI  - A case report with lymphangiomatosis of the colon.
AB  - The incidence of lymphangiomas in the gastrointestinal tract is low, particularly
      in the colon and rectum, and most cases are solitary. Lymphangiomatosis of the
      colon are encountered infrequently with only one report in the English
      literature, and polypectomy was performed for the diagnosis in that case report.
      However, trends in the diagnosis of lymphangiomatosis of colon have been changing
      since the development of endoscopic ultrasonography (EUS), and this case is the
      first in that lymphangiomatosis of the colon was diagnosed without invasive
      procedures. Here we describe the case of 31-yr-old woman with lymphangiomatosis
      of the colon with numerous polyposis-like appearing lesions diagnosed by
      endoscopic ultrasonography and a colonoscopy.

PMID- 20052364
TI  - A novel DHCR7 mutation in a Smith-Lemli-Opitz syndrome infant presenting with
      neonatal cholestasis.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome
      caused by a defect in cholesterol biosynthesis. The incidence is very low in
      Asians and only one case has been reported in Korea thus far. Recently, we found
      an infant with neonatal cholestasis. He had microcephaly, ambiguous genitalia,
      cleft palate, syndactyly of toes, patent ductus arteriosus and hypertrophic
      pyloric stenosis. The serum cholesterol was decreased and serum 7
      dehydrocholesterol was markedly elevated. Genetic analysis of the DHCR7 gene
      identified a novel missense mutation (Pro227Ser) as well as a known mutation
      (Gly303Arg) previously identified in a Japanese patient with SLOS. Although rare
      in Korea, SLOS should be considered in the differential diagnosis of neonatal
      cholestasis, especially in patients with multiple congenital anomalies and low
      serum cholesterol levels.

PMID- 20052365
TI  - Novel CFTR mutations in a Korean infant with cystic fibrosis and pancreatic
      insufficiency.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease that is very rare in
      Asians: only a few cases have been reported in Korea. We treated a female infant
      with CF who had steatorrhea and failure to thrive. Her sweat chloride
      concentration was 102.0 mM/L. Genetic analysis identified two novel mutations
      including a splice site mutation (c.1766+2T >C) and a frameshift mutation
      (c.3908dupA; Asn1303LysfsX6). Pancreatic enzyme replacement and fat-soluble
      vitamin supplementation enabled the patient to get a catch-up growth. This is the
      first report of a Korean patient with CF demonstrating pancreatic insufficiency.
      CF should therefore be considered in the differential diagnosis of infants with
      steatorrhea and failure to thrive.

PMID- 20052366
TI  - The L441P mutation of cystic fibrosis transmembrane conductance regulator and its
      molecular pathogenic mechanisms in a Korean patient with cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder usually found in
      populations of white Caucasian descent. CF is caused by mutations in the Cystic
      Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl
      was admitted complaining of coughing and greenish sputum. Chest radiographs and
      computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The
      patient had chronic diarrhea and poor weight gain, and the abdominal
      pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was
      confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis
      test. The chloride concentration of sweat samples taken from both forearms of the
      pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a
      comprehensive search for mutations in the CFTR gene, the patient was found to
      carry the non-synonymous L441P mutation in one allele. Molecular physiologic
      analysis of the L441P mutation of CFTR revealed that the L441P mutation
      completely abolished the CFTR Cl(-) channel activity by disrupting proper protein
      folding and membrane trafficking of CFTR protein. These results confirmed the
      pathogenicity of the L441P mutation of CFTR circulating in the Korean population.
      The possibility of CF should be suspected in patients with chronic
      bronchiectasis, although the frequency of CF is relatively rare in East Asia.

PMID- 20052367
TI  - Non-type I cystinuria associated with mental retardation and ataxia in a Korean
      boy with a new missence mutation(G173R) in the SLC7A9 gene.
AB  - Cystinuria is an inherited renal and intestinal disease characterized by
      defective amino acids reabsorption and cystine urolithiasis. It is unusually
      associated with neurologic symptoms. Mutations in two genes, SLC3A1 and SLC7A9,
      have been identified in cystinuric patients. This report presents a 13-yr-old boy
      with cystinuria who manifested difficulty in walking, ataxia, and mental
      retardation. Somatosensory evoked potential of posterior tibial nerve stimulation
      showed the central conduction dysfunction through the posterior column of spinal
      cord. He was diagnosed non-type I cystinuria by urinary amino acid analysis and
      oral cystine loading test. We screened him and his family for gene mutation by
      direct sequencing of SLC3A1 and SLC7A9 genes. In this patient, we identified new
      missence mutation G173R in SLC7A9 gene.

PMID- 20052368
TI  - Cervical epidural abscess in haemodialysis patients by catheter related
      infection: report of two cases.
AB  - Despite advances in neuroimaging and neurosurgical treatment modalities, spinal
      epidural abscess remains a challenging problem. Early diagnosis is often
      difficult and treatment is always delayed. Spinal epidural abscess usually
      develops in patients with predisposing factors such as IV drug abuse, senillity,
      diabetes mellitus, spinal attempts, alcoholism, immunosuppression, liver diseases
      and catheterizations. It is rarely seen in cervical region. A successful
      treatment is only possible with early diagnosis and accurate surgical and medical
      treatment. Optimal management is unclear and morbidity and mortality are
      significant. We present two adult haemodialysis patients with end-stage renal
      insufficiency who developed cervical epidural abscess following central venous
      catheter placement. Early surgical intervention is mandatory in cases those have
      progressive neurological deficit and spinal deformity, and this is also increases
      the success rate of medical therapy.

PMID- 20052369
TI  - Pediatric-onset dystonia associated with bilateral striatal necrosis and G14459A
      mutation in a Korean family: a case report.
AB  - We describe a Korean family presenting with pediatric-onset, progressive,
      generalized dystonia with bilateral striatal necrosis and the homoplasmic G14459A
      mutation in the mitochondrial ND6 gene. The G14459A mutation has been reported in
      families presenting with Leber hereditary optic neuropathy (LHON) alone, LHON
      plus dystonia, or pediatric-onset dystonia. The proband had shown dysarthria,
      progressive generalized dystonia, and spasticity at 5 yr. Brain MRI demonstrated
      bilateral striatal necrosis. Additional investigation of family members revealed
      the presence of homoplasmic G14459A mutation in asymptomatic individuals. The
      clinical manifestation of the homoplasmic G14459A mtDNA mutation within the same
      family showed asymptomatic or pediatric-onset dystonia, without optic neuropathy.
      This study reemphasizes that the G14459A mutation is a candidate mutation for
      maternally inherited dystonia, regardless of optic neuropathy, and supports the
      hypothesis that nuclear genes may play a role in modifying the clinical
      expression of mitochondrial disease.

PMID- 20052370
TI  - A case of recurrent neuro-Behcet's disease after tooth extraction.
AB  - We report a 39-yr-old man with neuro-Behcet's disease (NBD) in remission who
      developed left-sided ataxia with a sensory deficit about 10 days after tooth
      extraction. Several years ago, he experienced a similar episode of relapse after
      tooth extraction. Brain magnetic resonance imaging showed a newly developed right
      thalamic lesion. In cerebrospinal fluid, lymphocyte-dominant pleocytosis and mild
      elevation of IgG were found. Immunologic factors may be important in the
      pathogenesis of NBD because of the time delay between tooth extraction and
      relapse. Careful observation and prevention are needed before dental procedures
      in patients with NBD.

PMID- 20052371
TI  - Crusted (Norwegian) scabies following systemic and topical corticosteroid
      therapy.
AB  - It is a case study of a 62-yr-old female with crusted (Norwegian) scabies, which
      appeared during her treatment with systemic and topical corticosteroid therapy,
      under the diagnosis of erythroderma. In the same time, the patient had been
      suffered from hypothyoidism, and her skin changes were misdiagnosed, because it
      was thought that they are associated with her endocrine disorder. Suddenly,
      beside the erythema, her skin became hyperkeratotic, with widespread scaling over
      the trunk and limbs, and crusted lesions appeared on her scalp and ears. The
      microscopic examination of the skin scales with potassium hydroxide demonstrated
      numerous scabies mites and eggs. Repeated topical treatments with lindan, benzoyl
      benzoat and 10% precipitated sulphur ointment led to the complete resolution of
      her skin condition.

PMID- 20052372
TI  - CT evidence for subchondral trabecular injury of the femoral head in transient
      osteoporosis of the hip: a case report.
AB  - A 28-yr-old woman presented with both hip pain that started sequentially during
      the peripartum period. Diagnosis of transient osteoporosis of the hip (TOH) was
      made based on typical findings of plain radiographs and magnetic resonance
      images. The subchondral trabeculae of the femoral head were evaluated on serially
      taken coronal multiplanar reformation computerized tomogram images. At 4 weeks
      after pain onset, marked decrease in the sclerotic density with irregular
      discontinuation was observed in the primary compression trabeculae. At 12 weeks,
      a focal area of irregular thickening of trabeculae was observed. At 20 weeks,
      sclerotic density of trabeculae recovered markedly and the focal area of
      irregular trabecular thickening disappeared. At 1 yr, subchondral trabeculae
      recovered almost completely. The evidence of subchondral trabecular injury was
      observed in the femoral heads of TOH.

PMID- 20052373
TI  - Vulnerability to episodes of extreme weather: Butajira, Ethiopia, 1998-1999.
AB  - BACKGROUND: During 1999-2000, great parts of Ethiopia experienced a period of
      famine which was recognised internationally. The aim of this paper is to
      characterise the epidemiology of mortality of the period, making use of
      individual, longitudinal population-based data from the Butajira demographic
      surveillance site and rainfall data from a local site. METHODS: Vital statistics
      and household data were routinely collected in a cluster sample of 10 sub
      communities in the Butajira district in central Ethiopia. These were supplemented
      by rainfall and agricultural data from the national reporting systems. RESULTS:
      Rainfall was high in 1998 and well below average in 1999 and 2000. In 1998, heavy
      rains continued from April into October, in 1999 the small rains failed and the
      big rains lasted into the harvesting period. For the years 1998-1999, the
      mortality rate was 24.5 per 1,000 person-years, compared with 10.2 in the
      remainder of the period 1997-2001. Mortality peaks reflect epidemics of malaria
      and diarrhoeal disease. During these peaks, mortality was significantly higher
      among the poorer. CONCLUSIONS: The analyses reveal a serious humanitarian crisis
      with the Butajira population during 1998-1999, which met the CDC guideline crisis
      definition of more than one death per 10,000 per day. No substantial humanitarian
      relief efforts were triggered, though from the results it seems likely that the
      poorest in the farming communities are as vulnerable as the pastoralists in the
      North and East of Ethiopia. Food insecurity and reliance on subsistence
      agriculture continue to be major issues in this and similar rural communities.
      Epidemics of traditional infectious diseases can still be devastating, given
      opportunities in nutritionally challenged populations with little access to
      health care.

PMID- 20052374
TI  - Issues in health risk assessment of current and future heat extremes.
AB  - BACKGROUND: In assessing health risks relating to current and future heat
      extremes, it is important to include developing countries, because these
      countries are considered to be vulnerable to the impact of climate change due to
      inadequate public health infrastructure, nutritional status and so forth.
      However, it is usually difficult to obtain relevant information from these
      countries, also because of insufficient public health infrastructure. OBJECTIVES:
      We invented a method that can be used for developing countries to assess the
      health risks of current and future extremes, but there still are some issues. We
      introduce and discuss these issues. DESIGN: We analysed time-series data with non
      parametric regression models including generalised additive models, which
      controlled for time trends. RESULTS: When we controlled for year, the temperature
      mortality relation was V-shaped, but when we controlled for season as well as
      year, the left side of the V-shape disappeared. Our month-specific analysis also
      revealed that winter months had higher mortality rates than other months, but
      there was no relation between mortality rate and temperature within each month
      during winter. CONCLUSIONS: This suggests that, unlike heat effects, risks due to
      cold effects may not be ameliorated even if global warming occurs. We need to
      investigate the mechanism behind high mortality during winter months.

PMID- 20052375
TI  - Foreword.

PMID- 20052376
TI  - Effects of heat on workers' health and productivity in Taiwan.
AB  - BACKGROUND: The impact of global warming on population health is a growing
      concern and has been widely discussed. The issue of heat stress disorders and
      consequent productivity reduction among workers has not yet been widely
      addressed. Taiwan is an island straddling the Tropic of Cancer in the West
      Pacific and has both subtropical and tropical climates. As of 2008, the economy
      of Taiwan accounts for 1.1% of the world gross domestic product at purchasing
      power parity and is listed as 19th in the world and eighth in Asia, according to
      International Monetary Fund data. OBJECTIVE: The aim of this paper is to identify
      occupations at risk and the potential health impacts of heat on workers in
      Taiwan. DESIGN: Historical data relating to meteorology, population, the labour
      force and economy were obtained from publicly available databases from the
      Taiwanese government. RESULTS: Hot seasons with an average maximum temperature
      above 30 degrees C and relative humidity above 74%, lasting for four to six
      months from May to October, pose health threats to construction, farming and
      fishery workers. In particular, populations of ageing farmers and physically
      overloaded construction workers are the two most vulnerable worker categories in
      which high temperature impacts on health and productivity. CONCLUSIONS:
      Currently, regulations and preventive actions for heat relief are difficult to
      enforce for several reasons, including lack of equipment for measuring
      environmental conditions, lack of awareness of potential hazards and strict time
      constraints imposed on workers. There is an urgent need to systematically and
      comprehensively assess the impact of a warming climate on workers' health and
      productivity to provide effective prevention strategies for a better working and
      living environment in Taiwan.

PMID- 20052377
TI  - Maintaining health, comfort and productivity in heat waves.
AB  - BACKGROUND: The aim of this paper is to summarise what is known about human
      response to heat and to use this knowledge to provide guidance on how to maintain
      the health, comfort and performance of people in heat waves. DESIGN: The use of
      power and especially water are critical in providing cooling. A practical method
      of cooling people in a water bath is described. A warm bath slowly cooled will
      provide effective cooling but not thermal trauma. RESULT: It is concluded that
      for sedentary and light activities, it is not necessary to cool offices or homes
      below 25 degrees C for thermal comfort. CONCLUSION: To compare the costs due to
      loss of productivity caused by a heat wave, with the cost of taking action, more
      research is needed into the relationship between levels of heat stress and how
      much distraction and 'time off task' it causes.

PMID- 20052378
TI  - Heat stress assessment among workers in a Nicaraguan sugarcane farm.
AB  - BACKGROUND: Heat illness is a major cause of preventable morbidity worldwide.
      Workers exposed to intense heat can become unable to activate compensation
      mechanisms, putting their health at risk. Heat stress also has a direct impact on
      production by causing poor task performance and it increases the possibility of
      work-related morbidity and injuries. During the sugarcane harvest period, workers
      are exposed to excessive sunlight and heat from approximately 6 am to 3 pm. A
      first assessment of heat stress during the 2006/2007 harvesting season served to
      redesign the existing rehydration measures. In this project, sugarcane workers
      were provided with more rehydration solutions and water during their work
      schedule. OBJECTIVE: To assess heat stress preventive measures in order to
      improve existing rehydration strategies as a means of increasing productivity.
      METHODS: A small group of 22 workers were followed up for 15 days during working
      hours, from 6 am to 3 pm. Selection criteria were defined: to have worked more
      than 50% of the day's working schedule and to have worked for at least 10 days of
      the follow-up period. A simple data recollection sheet was used. Information
      regarding the amount of liquid intake was registered. Production output data was
      also registered. Temperature measurements were recorded by using a portable
      temperature monitoring device ('EasyLog', model EL-USB-2). RESULTS: The average
      temperature measurements were above the Nicaraguan Ministry of Labour thresholds.
      Seven workers drank 7-8 L of liquid, improving their production. Output
      production increased significantly (p=0.005) among those best hydrated, from 5.5
      to 8 tons of cut sugarcane per worker per day. CONCLUSIONS: Productivity improved
      with the new rehydration measures. Awareness among workers concerning heat stress
      prevention was increased.

PMID- 20052379
TI  - Local scale prediction of Plasmodium falciparum malaria transmission in an
      endemic region using temperature and rainfall.
AB  - BACKGROUND: To support malaria control strategies, prior knowledge of disease
      risk is necessary. Developing a model to explain the transmission of malaria, in
      endemic and epidemic regions, is of high priority in developing health system
      interventions. We develop, fit and validate a non-spatial dynamic model driven by
      meteorological conditions that can capture seasonal malaria transmission dynamics
      at the village level in a malaria holoendemic area of north-western Burkina Faso.
      METHODS: A total of 676 children aged 6-59 months took part in this study.
      Trained interviewers visited children at home weekly from December 2003 to
      November 2004 for Plasmodium falciparum malaria infection detection. Anopheles
      daily biting rate, mortality rate and growth rate were evaluated. Digital
      meteorological stations measured ambient temperature, humidity and rainfall in
      each site. RESULTS: The overall P. falciparum malaria infection incidence was 1.1
      episodes per person year. There was strong seasonal variation in P. falciparum
      malaria infection incidence with a peak observed in August and September,
      corresponding to the rainy season and a high number of mosquitoes. The model
      estimates of monthly mosquito abundance and the incidence of malaria infection
      correlated well with observed values. The fit was sensitive to daily mosquito
      survival and daily human parasite clearance. CONCLUSION: The model has
      demonstrated potential for local scale seasonal prediction of P. falciparum
      malaria infection. It could therefore be used to understand malaria transmission
      dynamics using meteorological parameters as the driving force and to help
      district health managers in identifying high-risk periods for more focused
      interventions.

PMID- 20052380
TI  - Climate variability and increase in intensity and magnitude of dengue incidence
      in Singapore.
AB  - INTRODUCTION: Dengue is currently a major public health burden in Asia Pacific
      Region. This study aims to establish an association between dengue incidence,
      mean temperature and precipitation, and further discuss how weather predictors
      influence the increase in intensity and magnitude of dengue in Singapore during
      the period 2000-2007. MATERIALS AND METHODS: Weekly dengue incidence data, daily
      mean temperature and precipitation and the midyear population data in Singapore
      during 2000-2007 were retrieved and analysed. We employed a time series Poisson
      regression model including time factors such as time trends, lagged terms of
      weather predictors, considered autocorrelation, and accounted for changes in
      population size by offsetting. RESULTS: The weekly mean temperature and
      cumulative precipitation were statistically significant related to the increases
      of dengue incidence in Singapore. Our findings showed that dengue incidence
      increased linearly at time lag of 5-16 and 5-20 weeks succeeding elevated
      temperature and precipitation, respectively. However, negative association
      occurred at lag week 17-20 with low weekly mean temperature as well as lag week 1
      4 and 17-20 with low cumulative precipitation. DISCUSSION: As Singapore
      experienced higher weekly mean temperature and cumulative precipitation in the
      years 2004-2007, our results signified hazardous impacts of climate factors on
      the increase in intensity and magnitude of dengue cases. The ongoing global
      climate change might potentially increase the burden of dengue fever infection in
      near future.

PMID- 20052381
TI  - Climate impacts on environmental risks evaluated from space: a conceptual
      approach to the case of Rift Valley Fever in Senegal.
AB  - BACKGROUND: Climate and environment vary across many spatio-temporal scales,
      including the concept of climate change, which impact on ecosystems, vector-borne
      diseases and public health worldwide. OBJECTIVES: To develop a conceptual
      approach by mapping climatic and environmental conditions from space and studying
      their linkages with Rift Valley Fever (RVF) epidemics in Senegal. DESIGN: Ponds
      in which mosquitoes could thrive were identified from remote sensing using high
      resolution SPOT-5 satellite images. Additional data on pond dynamics and rainfall
      events (obtained from the Tropical Rainfall Measuring Mission) were combined with
      hydrological in-situ data. Localisation of vulnerable hosts such as penned cattle
      (from QuickBird satellite) were also used. RESULTS: Dynamic spatio-temporal
      distribution of Aedes vexans density (one of the main RVF vectors) is based on
      the total rainfall amount and ponds' dynamics. While Zones Potentially Occupied
      by Mosquitoes are mapped, detailed risk areas, i.e. zones where hazards and
      vulnerability occur, are expressed in percentages of areas where cattle are
      potentially exposed to mosquitoes' bites. CONCLUSIONS: This new conceptual
      approach, using precise remote-sensing techniques, simply relies upon rainfall
      distribution also evaluated from space. It is meant to contribute to the
      implementation of operational early warning systems for RVF based on both natural
      and anthropogenic climatic and environmental changes. In a climate change
      context, this approach could also be applied to other vector-borne diseases and
      places worldwide.

PMID- 20052382
TI  - The cancer stem cell concept in progression of head and neck cancer.
AB  - Human head and neck cancer (HNC) is a highly heterogeneous disease. Understanding
      the biology of HNC progression is necessary for the development of novel
      approaches to its prevention, early detection, and treatment. A current
      evolutional progression model has limitations in explaining the heterogeneity
      observed in a single tumor nest. Accumulating evidence supports the existence of
      cancer stem cells (CSCs) as small subpopulations in solid tumors, including HNC.
      These CSCs can be selected by appropriate cell surface markers, which are cancer
      type specific and have been confirmed by unique in vitro and in vivo assays.
      Selected CSC populations maintain a self-renewal capability and show aggressive
      behaviors, such as chemoresistance and metastasis. In addition to introducing the
      CSC concept in solid tumors, this short review summarizes current publications in
      HNC CSC and the prospective development and application of the CSC concept to HNC
      in the clinic.

PMID- 20052383
TI  - Painless obstructive jaundice secondary to a common bile duct abscess: a delayed
      sequela of cholecystectomy.
AB  - Complications related to cholecystectomy are well described. Most occur in the
      early postoperative period and are recognised either at the time of, or shortly
      after surgery. Clinical sequelae occurring years following cholecystectomy are
      rare and infrequently reported. In addition, most delayed complications are
      related to the continuing presence or new formation of gallstones. In this paper
      we present a unique case of an abscess of the common bile duct wall, presenting
      with painless obstructive jaundice more than 30 years following an open
      cholecystectomy, without the presence of gallstones. The clinical presentation,
      investigations, and treatment are discussed with a review of other relevant
      reported cases in the literature.

PMID- 20052384
TI  - Histone deacetylase inhibitor therapy in epithelial ovarian cancer.
AB  - Since epigenetic alterations are believed to be involved in the repression of
      tumor suppressor genes and promotion of tumorigenesis in ovarian cancers, novel
      compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an
      attractive therapeutic approach. In this review, we discuss the biologic and
      therapeutic effects of HDAC inhibitors (HDACIs) in treating ovarian cancer.
      HDACIs were able to mediate inhibition of cell growth, cell cycle arrest,
      apoptosis, and expression of genes related to the malignant phenotype in a
      variety of ovarian cancer cell lines. Furthermore, HDACIs were able to induce the
      accumulation of acetylated histones in the chromatin of the p21(WAF1) gene in
      human ovarian carcinoma cells. In xenograft models, some of HDACIs have
      demonstrated antitumor activity with only few side effects. Some clinical trials
      demonstrate that HDACI drugs provide an important class of new mechanism-based
      therapeutics for ovarian cancer. In this review, we discuss the biologic and
      therapeutic effects of HDACIs in treating ovarian cancer, especially focusing on
      preclinical studies and clinical trials.

PMID- 20052385
TI  - Immunological and therapeutic strategies against salmonid cryptobiosis.
AB  - Salmonid cryptobiosis is caused by the haemoflagellate, Cryptobia salmositica.
      Clinical signs of the disease in salmon (Oncorhynchus spp.) include exophthalmia,
      general oedema, abdominal distension with ascites, anaemia, and anorexia. The
      disease-causing factor is a metalloprotease and the monoclonal antibody (mAb-001)
      against it is therapeutic. MAb-001 does not fix complement but agglutinates the
      parasite. Some brook charr, Salvelinus fontinalis cannot be infected (Cryptobia
      resistant); this resistance is controlled by a dominant Mendelian locus and is
      inherited. In Cryptobia-resistant charr the pathogen is lysed via the Alternative
      Pathway of Complement Activation. However, some charr can be infected and they
      have high parasitaemias with no disease (Cryptobia-tolerant). In infected
      Cryptobia-tolerant charr the metalloprotease is neutralized by a natural
      antiprotease, alpha2 macroglobulin. Two vaccines have been developed. A single
      dose of the attenuated vaccine protects 100% of salmonids (juveniles and adults)
      for at least 24 months. Complement fixing antibody production and cell-mediated
      response in vaccinated fish rise significantly after challenge. Fish injected
      with the DNA vaccine initially have slight anaemias but they recover and have
      agglutinating antibodies. On challenge, DNA-vaccinated fish have lower
      parasitaemias, delayed peak parasitaemias and faster recoveries. Isometamidium
      chloride is therapeutic against the pathogen and its effectiveness is increased
      after conjugation to antibodies.

PMID- 20052387
TI  - Interactive data mining for molecular graphs.
AB  - Designing new medical drugs for a specific disease requires extensive analysis of
      many molecules that have an activity for the disease. The main goal of these
      extensive analyses is to discover substructures (fragments) that account for the
      activity of these molecules. Once they are discovered, these fragments are used
      to understand the structure of new drugs and design new medicines for the
      disease. In this paper, we propose an interactive approach for visual molecule
      mining to discover fragments of molecules that are responsible for the desired
      activity with respect to a specific disease. Our approach visualizes molecular
      data in a form that can be interpreted by a human expert. Using a pipelining
      structure, it enables experts to contribute to the solution with their expertise
      at different levels. In order to derive desired fragments, it combines histogram
      based filtering and clustering methods in a novel way. This combination enables a
      flexible determination of frequent fragments that repeat in molecules exactly or
      with some variations.

PMID- 20052386
TI  - 5-Lipoxygenase DNA methylation and mRNA content in the brain and heart of young
      and old mice.
AB  - The expression of 5-lipoxygenase (5-LOX) is affected by aging and regulated by
      epigenetic mechanisms including DNA methylation. We used methylation-sensitive
      restriction endonucleases (AciI, BstUI, HpaII, and HinP1I) to assess 5-LOX DNA
      methylation in brain and heart tissue samples from young (2 months) and old (22
      months) mice. We also measured mRNA content for 5-LOX and the DNA
      methyltransferases DNMT1 and DNMT3a. In young mice, the 5-LOX mRNA content was
      significantly greater in the heart compared to the brain; 5-LOX DNA methylation
      was lower, except in the AciI assay in which it was higher in the heart. Aging
      decreased 5-LOX mRNA content in the heart and increased it in the brain. Aging
      also increased 5-LOX DNA methylation and this effect was site- (i.e., enzyme) and
      tissue-specific. Generally, DNMT1 and DNMT3a mRNA content was lower in the brain
      regions compared to the heart; the only effect of aging was observed in the mRNA
      content of DNMT3a, which was decreased in the heart of old mice. These results
      indicate a complex tissue-specific and aging-dependent interplay between the DNA
      methylation system and 5-LOX mRNA content. Interpretation of this data must take
      into account that the tissue samples contained a mixture of various cell types.

PMID- 20052388
TI  - How fast is the sessile ciona?
AB  - Genomewide analyses of distances between orthologous gene pairs from the ascidian
      species Ciona intestinalis and Ciona savignyi were compared with those of
      vertebrates. Combining this data with a detailed and careful use of vertebrate
      fossil records, we estimated the time of divergence between the two ascidians
      nearly 180 My. This estimation was obtained after correcting for the different
      substitution rates found comparing several groups of chordates; indeed we
      determine here that on average Ciona species evolve 50% faster than vertebrates.

PMID- 20052389
TI  - HPV prevalence in Colombian women with cervical cancer: implications for
      vaccination in a developing country.
AB  - Human Papillomavirus (HPV) vaccines have been considered potentially cost
      effective for the reduction of cervical cancer burden in developing countries;
      their effectiveness in a public health setting continues to be researched. We
      conducted an HPV prevalence survey among Colombian women with invasive cancer.
      Paraffin-embedded biopsies were obtained from one high-risk and one low-middle
      risk regions. GP5+/GP6+ L1 primers, RLB assays, and E7 type specific PCR were
      used for HPV-DNA detection. 217 cases were analyzed with 97.7% HPV detection
      rate. HPV-16/18 prevalence was 63.1%; HPV-18 had lower occurrence in the high
      risk population (13.8% versus 9.6%) allowing for the participation of less common
      HPV types; HPV-45 was present mainly in women under 50 and age-specific HPV type
      prevalence revealed significant differences. Multiple high-risk infections
      appeared in 16.6% of cases and represent a chance of replacement. Age-specific
      HPV prevalence and multiple high-risk infections might influence vaccine impact.
      Both factors highlight the role of HPVs other than 16/18, which should be
      considered in cost-effectiveness analyses for potential vaccine impact.

PMID- 20052390
TI  - Mizoribine: a new approach in the treatment of renal disease.
AB  - Mizoribine (MZB) is an imidazole nucleoside and an immunosuppressive agent. The
      immunosuppressive effect of MZB has been reported to be due to the inhibition of
      DNA synthesis in the S phase of the cell cycle. Because of its relative lack of
      toxicity, during the past decade MZB has been frequently used instead of
      azathioprine as a component of immunosuppressive drug regimens. MZB is being used
      to treat renal transplantation patients, IgA nephropathy, lupus erythematosus,
      and childhood nephrotic syndrome (NS), and some recent studies have assessed the
      efficacy of oral MZB pulse therapy for severe lupus nephritis, steroid-resistant
      NS, and frequently relapsing-steroid-dependent NS. This review summarizes the
      published findings on the efficacy of MZB for renal disease including IgA
      nephropathy, lupus nephritis, and NS, as well as of oral MZB pulse therapy for
      severe lupus nephritis and NS, and also the mechanism of the effect of oral MZB
      pulse therapy on the lymphocyte cell cycle.

PMID- 20052391
TI  - Segmentation of Pulmonary Vascular Trees from Thoracic 3D CT Images.
AB  - This paper describes an algorithm for extracting pulmonary vascular trees
      (arteries plus veins) from three-dimensional (3D) thoracic computed tomographic
      (CT) images. The algorithm integrates tube enhancement filter and traversal
      approaches which are based on eigenvalues and eigenvectors of a Hessian matrix to
      extract thin peripheral segments as well as thick vessels close to the lung
      hilum. The resultant algorithm was applied to a simulation data set and 44 scans
      from 22 human subjects imaged via multidetector-row CT (MDCT) during breath holds
      at 85% and 20% of their vital capacity. A quantitative validation was performed
      with more than 1000 manually identified points selected from inside the vessel
      segments to assess true positives (TPs) and 1000 points randomly placed outside
      of the vessels to evaluate false positives (FPs) in each case. On average, for
      both the high and low volume lung images, 99% of the points was properly marked
      as vessel and 1% of the points were assessed as FPs. Our hybrid segmentation
      algorithm provides a highly reliable method of segmenting the combined pulmonary
      venous and arterial trees which in turn will serve as a critical starting point
      for further quantitative analysis tasks and aid in our overall goal of
      establishing a normative atlas of the human lung.

PMID- 20052392
TI  - Cross-Talk between PPARs and the Partners of RXR: A Molecular Perspective.
AB  - The PPARs are integral parts of the RXR-dependent signaling networks. Many other
      nuclear receptor subfamily 1 members also require RXR as their obligatory
      heterodimerization partner and they are often co-expressed in any given tissue.
      Therefore, the PPARs often complete with other RXR-dependent nuclear receptors
      and this competition has important biological implications. Thorough
      understanding of this cross-talk at the molecular level is crucial to determine
      the detailed functional roles of the PPARs. At the level of DNA binding, most RXR
      heterodimers bind selectively to the well-known "DR1 to 5" DNA response elements.
      As a result, many heterodimers share the same DR element and must complete with
      each other for DNA binding. At the level of heterodimerization, the partners of
      RXR share the same RXR dimerization interface. As a result, individual nuclear
      receptors must complete with each other for RXR to form functional heterodimers.
      Cross-talk through DNA binding and RXR heterodimerization present challenges to
      the study of these nuclear receptors that cannot be adequately addressed by
      current experimental approaches. Novel tools, such as engineered nuclear
      receptors with altered dimerization properties, are currently being developed.
      These tools will enable future studies to dissect specific RXR heterodimers and
      their signaling pathways.

PMID- 20052393
TI  - A Comparison of the Proteomic Expression in Pooled Saliva Specimens from
      Individuals Diagnosed with Ductal Carcinoma of the Breast with and without Lymph
      Node Involvement.
AB  - Purpose. The objective was to compare the salivary protein profiles of saliva
      specimens from individuals diagnosed with invasive ductal carcinoma of the breast
      (IDC) with and without lymph node involvement. Methods. Three pooled saliva
      specimens from women were analyzed. One pooled specimen was from healthy women;
      another was from women diagnosed with Stage IIa IDC and a specimen from women
      diagnosed with Stage IIb. The pooled samples were trypsinized and the peptide
      digests labeled with the appropriate iTRAQ reagent. Labeled peptides from each of
      the digests were combined and analyzed by reverse phase capillary chromatography
      on an LC-MS/MS mass spectrometer. Results. The results yielded approximately 174
      differentially expressed proteins in the saliva specimens. There were 55 proteins
      that were common to both cancer stages in comparison to each other and healthy
      controls while there were 20 proteins unique to Stage IIa and 28 proteins that
      were unique to Stage IIb.

PMID- 20052394
TI  - Benign fibroepithelial polyp of renal pelvis in a patient with familial
      adenomatous polyposis: a successful percutaneous nephroscopic management
      strategy.
AB  - We present a rare case of a benign fibroepithelial polyp of the renal pelvis in a
      patient with familial adenomatous polyposis. In our paper we describe a new
      minimally invasive technique developed in our unit using an amplatz goose neck
      snare via a percutaneous nephroscope sheath in the management of the benign
      fibroepithelial polyp of the renal pelvis and present a current review of
      management strategies in literature.

PMID- 20052395
TI  - Composition and morphology of nanocrystals in urines of lithogenic patients and
      healthy persons.
AB  - The composition and morphology of nanocrystals in urines of healthy persons and
      lithogenic patients were comparatively investigated by means of X-ray diffraction
      (XRD) and transmission electron microscopy (TEM). It was shown that the main
      composition of urinary nanocrystals in healthy persons were calcium oxalate
      dihydrate (COD), uric acid, and ammonium magnesium phosphate (struvite). However,
      the main compositions of urinary nanocrystals in lithogenic patients were
      struvite, beta-tricalcium phosphate, uric acid, COD, and calcium oxalate
      monohydrate (COM). According to the XRD data, the size of nanocrystals was
      calculated to be 23 approximately 72 nm in healthy urine and 12 approximately 118
      nm in lithogenic urine by Scherer formula. TEM results showed that the
      nanocrystals in healthy urine were dispersive and uniform with a mean size of
      about 38 nm. In contrast, the nanocrystals in lithogenic urine were much
      aggregated with a mean size of about 55 nm. The results in this work indicated
      that the urinary stone formation may be prevented by diminishing the aggregation
      and the size differentiation of urinary nanocrystals by physical or chemical
      methods.

PMID- 20052396
TI  - Familial tuberculosis mimicking advanced ovarian cancer.
AB  - Genital TB may present as on abdominopelvic mass mimicking ovarian malignancy
      because clinical and laboratory findings are similar. Family history is very
      important and should be considered for differential diagnosis. Three cases of
      genital TB with presentation of abdominopelvic masses and with no signs and
      symptoms of TB were presented. Two of them had positive family history of
      pulmonary TB. Tissue diagnosis was the best method for diagnosis of genital TB,
      but it should be reminded that if positive family history of TB was present, mini
      laparotomy should be done to take biopsy and to make rapid diagnosis before
      treatment.

PMID- 20052397
TI  - Cost-effectiveness of universal prophylaxis in pregnancy with prior group B
      streptococci colonization.
AB  - OBJECTIVE: To estimate the costs and outcomes of rescreening for group B
      streptococci (GBS) compared to universal treatment of term women with history of
      GBS colonization in a previous pregnancy. STUDY DESIGN: A decision analysis model
      was used to compare costs and outcomes. Total cost included the costs of
      screening, intrapartum antibiotic prophylaxis (IAP), treatment for maternal
      anaphylaxis and death, evaluation of well infants whose mothers received IAP, and
      total costs for treatment of term neonatal early onset GBS sepsis. RESULTS: When
      compared to screening and treating, universal treatment results in more women
      treated per GBS case prevented (155 versus 67) and prevents more cases of early
      onset GBS (1732 versus 1700) and neonatal deaths (52 versus 51) at a lower cost
      per case prevented ($8,805 versus $12,710). CONCLUSION: Universal treatment of
      term pregnancies with a history of previous GBS colonization is more cost
      effective than the strategy of screening and treating based on positive culture
      results.

PMID- 20052398
TI  - What to do if standard therapy for hepatitis C fails.
AB  - The standard of care for treatment of individuals chronically infected with
      hepatitis C virus is pegylated interferon in combination with ribavirin. Efficacy
      is closely related to viral genotype. This review outlines potential therapeutic
      strategies for treatment failures and discusses some of the newer agents
      currently in development.

PMID- 20052399
TI  - Structural and functional brain abnormalities associated with developmental
      stuttering.

PMID- 20052400
TI  - Brain activity during altered auditory feedback: an FMRI study in healthy
      adolescents.

PMID- 20052401
TI  - In Vivo Therapeutic Silencing of Hypoxia-Inducible Factor 1 Alpha (HIF-1alpha)
      Using Single-Walled Carbon Nanotubes Noncovalently Coated with siRNA.
AB  - A new approach is described for delivering small interfering RNA (siRNA) into
      cancer cells by noncovalently complexing unmodified siRNA with pristine single
      walled carbon nanotubes (SWCNTs). The complexes were prepared by simple
      sonication of pristine SWCNTs in a solution of siRNA, which then served both as
      the cargo and as the suspending agent for the SWCNTs. When complexes containing
      siRNA targeted to hypoxia-inducible factor 1 alpha (HIF-1alpha) were added to
      cells growing in serum containing culture media, there was strong specific
      inhibition of cellular HIF-1alpha activity. The ability to obtain a biological
      response to SWCNT/siRNA complexes was seen in a wide variety of cancer cell
      types. Moreover, intratumoral administration of SWCNT-HIF-1alpha siRNA complexes
      in mice bearing MiaPaCa-2/HRE tumors significantly inhibited the activity of
      tumor HIF-1alpha. As elevated levels of HIF-1alpha are found in many human
      cancers and are associated with resistance to therapy and decreased patient
      survival, these results imply that SWCNT/siRNA complexes may have value as
      therapeutic agents.

PMID- 20052402
TI  - VALUING LOST HOME PRODUCTION OF DUAL EARNER COUPLES.
AB  - Using a life-cycle model in which women divide their time between home and market
      work, we establish a link between retirement wealth and the value of forgone home
      production. We use data from the Health and Retirement Study to estimate the
      model's parameters and adjust the growth rate of GDP to reflect reductions in non
      market output. We find that the value of forgone home production is modest -
      about 25 percent of women's measured earnings.

PMID- 20052403
TI  - Acute stress increases depolarization-evoked glutamate release in the rat
      prefrontal/frontal cortex: the dampening action of antidepressants.
AB  - BACKGROUND: Behavioral stress is recognized as a main risk factor for
      neuropsychiatric diseases. Converging evidence suggested that acute stress is
      associated with increase of excitatory transmission in certain forebrain areas.
      Aim of this work was to investigate the mechanism whereby acute stress increases
      glutamate release, and if therapeutic drugs prevent the effect of stress on
      glutamate release. METHODOLOGY/FINDINGS: Rats were chronically treated with
      vehicle or drugs employed for therapy of mood/anxiety disorders (fluoxetine,
      desipramine, venlafaxine, agomelatine) and then subjected to unpredictable
      footshock stress. Acute stress induced marked increase in depolarization-evoked
      release of glutamate from synaptosomes of prefrontal/frontal cortex in
      superfusion, and the chronic drug treatments prevented the increase of glutamate
      release. Stress induced rapid increase in the circulating levels of
      corticosterone in all rats (both vehicle- and drug-treated), and glutamate
      release increase was blocked by previous administration of selective antagonist
      of glucocorticoid receptor (RU 486). On the molecular level, stress induced
      accumulation of presynaptic SNARE complexes in synaptic membranes (both in
      vehicle- and drug-treated rats). Patch-clamp recordings of pyramidal neurons in
      the prefrontal cortex revealed that stress increased glutamatergic transmission
      through both pre- and postsynaptic mechanisms, and that antidepressants may
      normalize it by reducing release probability. CONCLUSIONS/SIGNIFICANCE: Acute
      footshock stress up-regulated depolarization-evoked release of glutamate from
      synaptosomes of prefrontal/frontal cortex. Stress-induced increase of glutamate
      release was dependent on stimulation of glucocorticoid receptor by
      corticosterone. Because all drugs employed did not block either elevation of
      corticosterone or accumulation of SNARE complexes, the dampening action of the
      drugs on glutamate release must be downstream of these processes. This novel
      effect of antidepressants on the response to stress, shown here for the first
      time, could be related to the therapeutic action of these drugs.

PMID- 20052404
TI  - Magnetic resonance water proton relaxation in protein solutions and tissue:
      T(1rho) dispersion characterization.
AB  - BACKGROUND: Image contrast in clinical MRI is often determined by differences in
      tissue water proton relaxation behavior. However, many aspects of water proton
      relaxation in complex biological media, such as protein solutions and tissue are
      not well understood, perhaps due to the limited empirical data. PRINCIPAL
      FINDINGS: Water proton T(1), T(2), and T(1rho) of protein solutions and tissue
      were measured systematically under multiple conditions. Crosslinking or
      aggregation of protein decreased T(2) and T(1rho), but did not change high-field
      T(1). T(1rho) dispersion profiles were similar for crosslinked protein solutions,
      myocardial tissue, and cartilage, and exhibited power law behavior with
      T(1rho)(0) values that closely approximated T(2). The T(1rho) dispersion of
      mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5
      kHz that was sensitive to changes in pH. The T(1rho) dispersion of crosslinked
      BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5
      kHz but showed decreased dispersion below 5 kHz. CONCLUSIONS: Proton exchange is
      a minor pathway for tissue T(1) and T(1rho) relaxation above 5 kHz. Potential
      models for relaxation are discussed, however the same molecular mechanism appears
      to be responsible across 5 decades of frequencies from T(1rho) to T(1).

PMID- 20052406
TI  - Acute Hydrocephalus due to Secondary Leptomeningeal Dissemination of an
      Anaplastic Oligodendroglioma.
AB  - Secondary leptomeningeal dissemination of oligodendroglioma is very rare. We
      report the case of a 38-year-old Caucasian male who presented with acute
      hydrocephalus. 8 months before, the patient had undergone craniotomy for right
      frontal anaplastic oligodendroglioma, WHO grade III. By that time, there was no
      evidence of tumor dissemination. MRI now ruled out local tumor progression but
      revealed meningeal contrast enhancement along the medulla, the myelon, and the
      cauda equina. Repeated lumbar puncture revealed increased cerebro-spinal fluid
      (CSF) pressure and protein content. Malignant cells were not detectable. Surgical
      treatment consisted in (1) placement of an ommaya reservoir for daily CSF
      puncture, (2) Spinal dural biopsy confirming leptomeningeal oligodendroglioma
      metastasis, and (3) ventriculo-peritoneal shunt placement after CSF protein has
      decreased to 1500-2000 mg/l.

PMID- 20052405
TI  - A strategy for eliciting antibodies against cryptic, conserved, conformationally
      dependent epitopes of HIV envelope glycoprotein.
AB  - BACKGROUND: Novel strategies are needed for the elicitation of broadly
      neutralizing antibodies to the HIV envelope glycoprotein, gp120. Experimental
      evidence suggests that combinations of antibodies that are broadly neutralizing
      in vitro may protect against challenge with HIV in nonhuman primates, and a small
      number of these antibodies have been selected by repertoire sampling of B cells
      and by the fractionation of antiserum from some patients with prolonged disease.
      Yet no additional strategies for identifying conserved epitopes, eliciting
      antibodies to these epitopes, and determining whether these epitopes are
      accessible to antibodies have been successful to date. The defining of additional
      conserved, accessible epitopes against which one can elicit antibodies will
      increase the probability that some may be the targets of broadly neutralizing
      antibodies. METHODOLOGY/PRINCIPAL FINDINGS: We postulate that additional cryptic
      epitopes of gp120 are present, against which neutralizing antibodies might be
      elicited even though these antibodies are not elicited by gp120, and that many of
      these epitopes may be accessible to antibodies should they be formed. We
      demonstrate a strategy for eliciting antibodies in mice against selected cryptic,
      conformationally dependent conserved epitopes of gp120 by immunizing with
      multiple identical copies of covalently linked peptides (MCPs). This has been
      achieved with MCPs representing 3 different domains of gp120. We show that some
      cryptic epitopes on gp120 are accessible to the elicited antibodies, and some
      epitopes in the CD4 binding region are not accessible. The antibodies bind to
      gp120 with relatively high affinity, and bind to oligomeric gp120 on the surface
      of infected cells. CONCLUSIONS/SIGNIFICANCE: Immunization with MCPs comprised of
      selected peptides of HIV gp120 is able to elicit antibodies against conserved,
      conformationally dependent epitopes of gp120 that are not immunogenic when
      presented as gp120. Some of these cryptic epitopes are accessible to the elicited
      antibodies.

PMID- 20052407
TI  - Life Threatening Complication during Treatment of Erysipelas due to Undiagnosed
      Ischemia of the Calf.
AB  - Erysipelas is a superficial skin infection due to streptococci strains, which
      usually responds well to conservative treatment. Coexisting undiagnosed ischemia
      of the extremity may lead to severe complications. 57-year-old man developed
      large, circumflex ulceration of his right calf within two weeks before the
      admission after three-month treatment of erysipelas. Computer angiography showed
      chronic occlusion of the superficial femoral artery and the above knee popliteal
      artery. Rapid debridement of the wound took control over the infection. Patient
      required complex vascular procedure which allowed to prepare the ulcer for meshed
      skin grafts. Patient was discharged home on 64th hospital day with completely
      healed ulcer.

PMID- 20052408
TI  - A strategy for the proliferation of Ulva prolifera, main causative species of
      green tides, with formation of sporangia by fragmentation.
AB  - Ulva prolifera, a common green seaweed, is one of the causative species of green
      tides that occurred frequently along the shores of Qingdao in 2008 and had
      detrimental effects on the preparations for the 2008 Beijing Olympic Games
      sailing competition, since more than 30 percent of the area of the games was
      invaded. In view of the rapid accumulation of the vast biomass of floating U.
      prolifera in green tides, we investigated the formation of sporangia in disks of
      different diameters excised from U. prolifera, changes of the photosynthetic
      properties of cells during sporangia formation, and development of spores. The
      results suggested that disks less than 1.00 mm in diameter were optimal for the
      formation of sporangia, but there was a small amount of spore release in these.
      The highest percentage of area of spore release occurred in disks that were 2.50
      mm in diameter. In contrast, sporangia were formed only at the cut edges of
      larger disks (3.00 mm, 3.50 mm, and 4.00 mm in diameter). Additionally, the
      majority of spores liberated from the disks appeared vigorous and developed
      successfully into new individuals. These results implied that fragments of the
      appropriate size from the U. prolifera thalli broken by a variety of factors via
      producing spores gave rise to the rapid proliferation of the seaweed under field
      conditions, which may be one of the most important factors to the rapid
      accumulation of the vast biomass of U. prolifera in the green tide that occurred
      in Qingdao, 2008.

PMID- 20052409
TI  - Transglutaminase 2, a novel regulator of eicosanoid production in asthma revealed
      by genome-wide expression profiling of distinct asthma phenotypes.
AB  - BACKGROUND: A frequent manifestation of asthma, exercise-induced
      bronchoconstriction (EIB), occurs in 30-50% of asthmatics and is characterized by
      increased release of inflammatory eicosanoids. The objective of this study was to
      identify genes differentially expressed in EIB and to understand the function of
      these genes in the biology of asthma. METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide
      expression profiling of airway leukocytes and epithelial cells obtained by
      induced sputum was conducted in two groups of subjects with asthma with and
      without EIB (n = 7 per group), at baseline and following exercise challenge.
      Based on the results of the gene expression study, additional comparisons were
      made with a normal control group (n = 10). Localization studies were conducted on
      epithelial brushings and biopsies from an additional group of asthmatics with EIB
      (n = 3). Genes related to epithelial repair and mast cell infiltration including
      beta-tryptase and carboxypeptidase A3 were upregulated by exercise challenge in
      the asthma group with EIB. A gene novel to asthma pathogenesis, transglutaminase
      2 (TGM2), was the most differentially expressed at baseline between the groups.
      In vivo studies confirmed the increased expression of TGM2 in airway cells and
      airway lining fluid, and demonstrate that TGM2 is avidly expressed in the
      asthmatic airway epithelium. In vitro studies using recombinant human enzymes
      reveal that TGM2 augments the enzymatic activity of secreted phospholipase A(2)
      (PLA(2)) group X (sPLA(2)-X), an enzyme recently implicated in asthma
      pathogenesis. CONCLUSIONS/SIGNIFICANCE: This study found that TGM2, a mediator
      that is novel to asthma pathogenesis, is overexpressed in asthmatic airways and
      functions to increase sPLA(2)-X enzymatic activity. Since PLA(2) serves as the
      first rate-limiting step leading to eicosanoid formation, these results suggest
      that TGM2 may be a key initiator of the airway inflammatory cascade in asthma.

PMID- 20052410
TI  - Mild hypoxia enhances proliferation and multipotency of human neural stem cells.
AB  - BACKGROUND: Neural stem cells (NSCs) represent an optimal tool for studies and
      therapy of neurodegenerative diseases. We recently established a v-myc
      immortalized human NSC (IhNSC) line, which retains stem properties comparable to
      parental cells. Oxygen concentration is one of the most crucial environmental
      conditions for cell proliferation and differentiation both in vitro and in vivo.
      In the central nervous system, physiological concentrations of oxygen range from
      0.55 to 8% oxygen. In particular, in the in the subventricular zone niche area,
      it's estimated to be 2.5 to 3%. METHODOLOGY/PRINCIPAL FINDINGS: We investigated
      in vitro the effects of 1, 2.5, 5, and 20% oxygen concentrations on IhNSCs both
      during proliferation and differentiation. The highest proliferation rate,
      evaluated through neurosphere formation assay, was obtained at 2.5 and 5% oxygen,
      while 1% oxygen was most noxious for cell survival. The differentiation assays
      showed that the percentages of beta-tubIII+ or MAP2+ neuronal cells and of GalC+
      oligodendrocytes were significantly higher at 2.5% compared with 1, 5, or 20%
      oxygen at 17 days in vitro. Mild hypoxia (2.5 to 5% oxygen) promoted
      differentiation into neuro-oligodendroglial progenitors as revealed by the higher
      percentage of MAP2+/Ki67+ and GalC+/Ki67+ residual proliferating progenitors, and
      enhanced the yield of GABAergic and slightly of glutamatergic neurons compared to
      1% and 20% oxygen where a significant percentage of GFAP+/nestin+ cells were
      still present at 17 days of differentiation. CONCLUSIONS/SIGNIFICANCE: These
      findings raise the possibility that reduced oxygen levels occurring in neuronal
      disorders like cerebral ischemia transiently lead to NSC remaining in a state of
      quiescence. Conversely, mild hypoxia favors NSC proliferation and neuronal and
      oligodendroglial differentiation, thus providing an important advance and a
      useful tool for NSC-mediated therapy of ischemic stroke and neurodegenerative
      diseases like Parkinson's disease, multiple sclerosis, and Alzheimer's disease.

PMID- 20052411
TI  - Myosin II motor proteins with different functions determine the fate of
      lamellipodia extension during cell spreading.
AB  - Non-muscle cells express multiple myosin-II motor proteins myosin IIA, myosin IIB
      and myosin IIC transcribed from different loci in the human genome. Due to a
      significant homology in their sequences, these ubiquitously expressed myosin II
      motor proteins are believed to have overlapping cellular functions, but the
      mechanistic details are not elucidated. The present study uncovered a mechanism
      that coordinates the distinctly localized myosin IIA and myosin IIB with
      unexpected opposite mechanical roles in maneuvering lamellipodia extension, a
      critical step in the initiation of cell invasion, spreading, and migration.
      Myosin IIB motor protein by localizing at the front drives lamellipodia extension
      during cell spreading. On the other hand, myosin IIA localizes next to myosin IIB
      and attenuates or retracts lamellipodia extension. Myosin IIA and IIB increase
      cell adhesion by regulating focal contacts formation in the spreading margins and
      central part of the spreading cell, respectively. Spreading cells expressing both
      myosin IIA and myosin IIB motor proteins display an organized actin network
      consisting of retrograde filaments, arcs and central filaments attached to focal
      contacts. This organized actin network especially arcs and focal contacts
      formation in the spreading margins were lost in myosin IIA cells. Surprisingly,
      myosin IIB cells displayed long parallel actin filaments connected to focal
      contacts in the spreading margins. Thus, with different roles in the regulation
      of the actin network and focal contacts formation, both myosin IIA and IIB
      determine the fate of lamellipodia extension during cell spreading.

PMID- 20052412
TI  - Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via
      iNOS/netrin-1/PKC pathway.
AB  - BACKGROUND: We hypothesized that genetic modification of mesenchymal stem cells
      (MSCs) with Sonic Hedgehog (Shh) transgene, a morphogen during embryonic
      development and embryonic and adult stem cell growth, improved their survival and
      angiogenic potential in the ischemic heart via iNOS/netrin/PKC pathway.
      METHODS/PRINCIPAL FINDINGS: MSCs from young Fisher-344 rat bone marrow were
      purified and transfected with pCMV Shh plasmid ((Shh)MSCs). Immunofluorescence,
      RT-PCR and Western blotting showed higher expression of Shh in (Shh)MSCs which
      also led to increased expression of angiogenic and pro-survival growth factors in
      (Shh)MSCs. Significantly improved migration and tube formation was seen in
      (Shh)MSCs as compared to empty vector transfected MSCs ((Emp)MSCs). Significant
      upregulation of netrin-1 and iNOS was observed in (Shh)MSCs in PI3K independent
      but PKC dependent manner. For in vivo studies, acute myocardial infarction model
      was developed in Fisher-344 rats. The animals were grouped to receive 70 microl
      basal DMEM without cells (group-1) or containing 1x10(6) (Emp)MSCs (group-2) and
      (Shh)MSCs (group-3). Group-4 received recombinant netrin-1 protein injection into
      the infarcted heart. FISH and sry-quantification revealed improved survival of
      (Shh)MSCs post engraftment. Histological studies combined with fluorescent
      microspheres showed increased density of functionally competent blood vessels in
      group-3 and group-4. Echocardiography showed significantly preserved heart
      function indices post engraftment with (Shh)MSCs in group-3 animals.
      CONCLUSIONS/SIGNIFICANCE: Reprogramming of stem cells with Shh maximizes their
      survival and angiogenic potential in the heart via iNOS/netrin-1/PKC signaling.

PMID- 20052413
TI  - Double positive CD4CD8 alphabeta T cells: a new tumor-reactive population in
      human melanomas.
AB  - BACKGROUND: Double positive (DP) CD4CD8 Talphabeta cells have been reported in
      normal individuals as well as in different pathological conditions including
      inflammatory diseases, viral infections and cancer, but their function remains to
      be elucidated. We recently reported the increased frequency of DP Talphabeta
      cells in human breast pleural effusions. This manuscript addresses the question
      of the existence and above all the role of this non-conventional DP sub
      population among tumor associated lymphocytes in melanomas. METHODOLOGY/PRINCIPAL
      FINDINGS: We analyzed the intratumoral cell infiltrate in solid metastasis (n =
      6) and tumor invaded lymph nodes (n = 26) samples from melanomas patients by
      multiparametric cytometry. Here we documented for the first time significant
      increased frequency of DP T cells in about 60% of melanoma tumors compared to
      blood samples. Interestingly, a high proportion of these cells produced TNF-alpha
      in response to autologous melanoma cell lines. Besides, they are characterized by
      a unique cytokine profile corresponding to higher secretion of IL-13, IL-4 and IL
      5 than simple positive T cells. In deep analysis, we derived a representative
      tumor-reactive DP T cell clone from a melanoma patient's invaded lymph node. This
      clone was restricted by HLA-A*2402 and recognized both autologous and allogeneic
      tumor cells of various origins as well as normal cells, suggesting that the
      target antigen was a ubiquitous self antigen. However, this DP T cell clone
      failed to kill HLA-A*2402 EBV-transformed B cells, probably due to the
      constitutive expression of immunoproteasome by these cells.
      CONCLUSIONS/SIGNIFICANCE: In conclusion, we can postulate that, according to
      their broad tumor reactivity and to their original cytokine profile, the tumor
      associated DP T cells could participate in immune responses to tumors in vivo.
      Therefore, the presence of these cells and their role will be crucial to address
      in cancer patients, especially in the context of immunotherapies.

PMID- 20052415
TI  - Occlusion of inferior vena cava: a singular presentation of abdominal aortic
      aneurysm.
AB  - Even though the majority of abdominal aortic aneurysm s(AAAs) are asymptomatic,
      they can occasionally manifest as a result of adjacent structures involvement.
      Although the most frequent venous complication of AAA is rupture into the
      inferior vena cava (IVC), venous compression can infrequently occur. The authors
      report a particularly rare case of compression and thrombosis of the IVC by AAA.
      Patient was treated by preoperative placement of an IVC filter to impede
      pulmonary embolism and subsequently by open surgical repair. Besides discussing
      the circumstances associated with IVC compression by AAA, the authors also
      discuss the treatment strategy adopted and the possible alternatives.

PMID- 20052414
TI  - Nanostructural and transcriptomic analyses of human saliva derived exosomes.
AB  - BACKGROUND: Exosomes, derived from endocytic membrane vesicles are thought to
      participate in cell-cell communication and protein and RNA delivery. They are
      ubiquitous in most body fluids (breast milk, saliva, blood, urine, malignant
      ascites, amniotic, bronchoalveolar lavage, and synovial fluids). In particular,
      exosomes secreted in human saliva contain proteins and nucleic acids that could
      be exploited for diagnostic purposes. To investigate this potential use, we
      isolated exosomes from human saliva and characterized their structural and
      transcriptome contents. METHODOLOGY: Exosomes were purified by differential
      ultracentrifugation and identified by immunoelectron microscopy (EM), flow
      cytometry, and Western blot with CD63 and Alix antibodies. We then described the
      morphology, shape, size distribution, and density using atomic force microscopy
      (AFM). Microarray analysis revealed that 509 mRNA core transcripts are relatively
      stable and present in the exosomes. Exosomal mRNA stability was determined by
      detergent lysis with RNase A treatment. In vitro, fluorescently labeled saliva
      exosomes could communicate with human keratinocytes, transferring their genetic
      information to human oral keratinocytes to alter gene expression at a new
      location. CONCLUSION: Our findings are consistent with the hypothesis that
      exosomes shuttle RNA between cells and that the RNAs present in the exosomes may
      be a possible resource for disease diagnostics.

PMID- 20052416
TI  - Chk1 haploinsufficiency results in anemia and defective erythropoiesis.
AB  - BACKGROUND: Erythropoiesis is a highly regulated and well-characterized
      developmental process responsible for providing the oxygen transport system of
      the body. However, few of the mechanisms involved in this process have been
      elucidated. Checkpoint Kinase 1 (Chk1) is best known for its role in the cell
      cycle and DNA damage pathways, and it has been shown to play a part in several
      pathways which when disrupted can lead to anemia. METHODOLOGY/PRINCIPAL FINDINGS:
      Here, we show that haploinsufficiency of Chk1 results in 30% of mice developing
      anemia within the first year of life. The anemic Chk1+/- mice exhibit distorted
      spleen and bone marrow architecture, and abnormal erythroid progenitors.
      Furthermore, Chk1+/- erythroid progenitors exhibit an increase in spontaneous DNA
      damage foci and improper contractile actin ring formation resulting in aberrant
      enucleation during erythropoiesis. A decrease in Chk1 RNA has also been observed
      in patients with refractory anemia with excess blasts, further supporting a role
      for Chk1 in clinical anemia. CONCLUSIONS/SIGNIFICANCE: Clinical trials of Chk1
      inhibitors are currently underway to treat cancer, and thus it will be important
      to track the effects of these drugs on red blood cell development over an
      extended period. Our results support a role for Chk1 in maintaining the balance
      between erythroid progenitors and enucleated erythroid cells during
      differentiation. We show disruptions in Chk1 levels can lead to anemia.

PMID- 20052417
TI  - Disordered microbial communities in asthmatic airways.
AB  - BACKGROUND: A rich microbial environment in infancy protects against asthma [1],
      [2] and infections precipitate asthma exacerbations [3]. We compared the airway
      microbiota at three levels in adult patients with asthma, the related condition
      of COPD, and controls. We also studied bronchial lavage from asthmatic children
      and controls. PRINCIPAL FINDINGS: We identified 5,054 16S rRNA bacterial
      sequences from 43 subjects, detecting >70% of species present. The bronchial tree
      was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2)
      surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were
      much more frequent in bronchi of adult asthmatics or patients with COPD than
      controls. We found similar highly significant increases in Proteobacteria in
      asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were
      more frequent in controls than adult or child asthmatics or COPD patients.
      SIGNIFICANCE: The results show the bronchial tree to contain a characteristic
      microbiota, and suggest that this microbiota is disturbed in asthmatic airways.

PMID- 20052418
TI  - Site and strain-specific variation in gut microbiota profiles and metabolism in
      experimental mice.
AB  - BACKGROUND: The gastrointestinal tract microbiota (GTM) of mammals is a complex
      microbial consortium, the composition and activities of which influences mucosal
      development, immunity, nutrition and drug metabolism. It remains unclear whether
      the composition of the dominant GTM is conserved within animals of the same
      strain and whether stable GTMs are selected for by host-specific factors or
      dictated by environmental variables. METHODOLOGY/PRINCIPAL FINDINGS: The GTM
      composition of six highly inbred, genetically distinct strains of mouse (C3H,
      C57, GFEC, CD1, CBA nu/nu and SCID) was profiled using eubacterial -specific PCR
      DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal
      eubacterial profiles that were highly stable (c. >95% concordance over 26 months
      for C57). Analyses of mice that had been relocated before and after maturity
      indicated marked, reproducible changes in fecal consortia and that occurred only
      in young animals. Implantation of a female BDF1 mouse with genetically distinct
      (C57 and Agoutie) embryos produced highly similar GTM profiles (c. 95%
      concordance) between mother and offspring, regardless of offspring strain, which
      was also reflected in urinary metabolite profiles. Marked institution-specific
      GTM profiles were apparent in C3H mice raised in two different research
      institutions. CONCLUSION/SIGNIFICANCE: Strain-specific data were suggestive of
      genetic determination of the composition and activities of intestinal symbiotic
      consortia. However, relocation studies and uterine implantation demonstrated the
      dominance of environmental influences on the GTM. This was manifested in large
      variations between isogenic adult mice reared in different research institutions.

PMID- 20052419
TI  - In situ patrolling of regulatory T cells is essential for protecting autoimmune
      exocrinopathy.
AB  - BACKGROUND: Migration of T cells, including regulatory T (Treg) cells, into the
      secondary lymph organs is critically controlled by chemokines and adhesion
      molecules. However, the mechanisms by which Treg cells regulate organ-specific
      autoimmunity via these molecules remain unclear. Although we previously reported
      autoimmune exocrinopathy resembling Sjogren's syndrome (SS) in the lacrimal and
      salivary glands from C-C chemokine receptor 7 (CCR7)-deficient mice, it is still
      unclear whether CCR7 signaling might specifically affect the dynamics and
      functions of Treg cells in vivo. We therefore investigated the cellular mechanism
      for suppressive function of Treg cells via CCR7 in autoimmunity using mouse
      models and human samples. METHODS AND FINDINGS: Patrolling Treg cells were
      detected in the exocrine organs such as lacrimal and salivary glands from normal
      mice that tend to be targets for autoimmunity while the Treg cells were almost
      undetectable in the exocrine glands of CCR7(-/-) mice. In addition, we found the
      significantly increased retention of CD4(+)CD25(+)Foxp3(+) Treg cells in the
      lymph nodes of CCR7(-/-) mice with aging. Although Treg cell egress requires
      sphingosine 1-phosphate (S1P), chemotactic function to S1P of CCR7-/- Treg cells
      was impaired compared with that of WT Treg cells. Moreover, the in vivo
      suppression activity was remarkably diminished in CCR7(-/-) Treg cells in the
      model where Treg cells were co-transferred with CCR7(-/-) CD25(-)CD4(+) T cells
      into Rag2(-/-) mice. Finally, confocal analysis showed that CCR7(+)Treg cells
      were detectable in normal salivary glands while the number of CCR7(+)Treg cells
      was extremely decreased in the tissues from patients with Sjogren's syndrome.
      CONCLUSIONS: These results indicate that CCR7 essentially governs the patrolling
      functions of Treg cells by controlling the traffic to the exocrine organs for
      protecting autoimmunity. Characterization of this cellular mechanism could have
      clinical implications by supporting development of new diagnosis or treatments
      for the organ-specific autoimmune diseases such as Sjogren's syndrome and
      clarifying how the local immune system regulates autoimmunity.

PMID- 20052420
TI  - Climate change, its impact on human health in the Arctic and the public health
      response to threats of emerging infectious diseases.

PMID- 20052421
TI  - Climate change and population health in Africa: where are the scientists?
AB  - Despite a growing awareness of Africans' vulnerability to climate change, there
      is relatively little empirical evidence published about the effects of climate on
      population health in Africa. This review brings together some of the generalised
      predictions about the potential continent-wide effects of climate change with
      examples of the relatively few locally documented population studies in which
      climate change and health interact. Although ecologically determined diseases
      such as malaria are obvious candidates for susceptibility to climate change,
      wider health effects also need to be considered, particularly among populations
      where adequacy of food and water supplies may already be marginal.

PMID- 20052422
TI  - Workplace heat stress, health and productivity - an increasing challenge for low
      and middle-income countries during climate change.
AB  - BACKGROUND: Global climate change is already increasing the average temperature
      and direct heat exposure in many places around the world. OBJECTIVES: To assess
      the potential impact on occupational health and work capacity for people exposed
      at work to increasing heat due to climate change. DESIGN: A brief review of basic
      thermal physiology mechanisms, occupational heat exposure guidelines and heat
      exposure changes in selected cities. RESULTS: In countries with very hot seasons,
      workers are already affected by working environments hotter than that with which
      human physiological mechanisms can cope. To protect workers from excessive heat,
      a number of heat exposure indices have been developed. One that is commonly used
      in occupational health is the Wet Bulb Globe Temperature (WBGT). We use WBGT to
      illustrate assessing the proportion of a working hour during which a worker can
      sustain work and the proportion of that same working hour that (s)he needs to
      rest to cool the body down and maintain core body temperature below 38 degrees C.
      Using this proportion a 'work capacity' estimate was calculated for selected heat
      exposure levels and work intensity levels. The work capacity rapidly reduces as
      the WBGT exceeds 26-30 degrees C and this can be used to estimate the impact of
      increasing heat exposure as a result of climate change in tropical countries.
      CONCLUSIONS: One result of climate change is a reduced work capacity in heat
      exposed jobs and greater difficulty in achieving economic and social development
      in the countries affected by this somewhat neglected impact of climate change.

PMID- 20052423
TI  - Invited Editorial: Health as a crucial driver for climate policy.

PMID- 20052424
TI  - Meningococcal disease and climate.

PMID- 20052425
TI  - The 'Hothaps' programme for assessing climate change impacts on occupational
      health and productivity: an invitation to carry out field studies.
AB  - The 'high occupational temperature health and productivity suppression' programme
      (Hothaps) is a multi-centre health research and prevention programme aimed at
      quantifying the extent to which working people are affected by, or adapt to, heat
      exposure while working, and how global heating during climate change may increase
      such effects. The programme will produce essential new evidence for local,
      national and global assessment of negative impacts of climate change that have
      largely been overlooked. It will also identify and evaluate preventive
      interventions in different social and economic settings.Hothaps includes studies
      in any part of the world where hourly heat exposure exceeds physiological stress
      limits that may affect workers. This usually happens at temperatures above 25
      degrees C, depending on humidity, wind movement and heat radiation. Working
      people in low and middle-income tropical countries are particularly vulnerable,
      because many of them are involved in heavy physical work, either outdoors in
      strong sunlight or indoors without effective cooling. If high work intensity is
      maintained in workplaces with high heat exposure, serious health effects can
      occur, including heat stroke and death.Depending on the type of occupation, the
      required work intensity, and the level of heat stress, working people have to
      slow down their work in order to reduce internal body heat production and the
      risk of heat stroke. Thus, unless preventive interventions are used to reduce the
      heat stress on workers, their individual health and productivity will be affected
      and economic output per work hour will be reduced. Heat also influences other
      daily physical activities, unrelated to work, in all age groups. Poorer people
      without access to household or workplace cooling devices are most likely to be
      affected.The Hothaps programme includes a pilot study, heat monitoring of
      selected workplaces, qualitative studies of perceived heat impacts and
      preventative interventions, quantitative studies of impacts on health and
      productivity, and assessments of local impacts of climate change taking into
      account different applications of preventative interventions.Fundraising for the
      global programme is in progress and has enabled local field studies to start in
      2009. Local funding support is also of great value and is being sought by several
      interested scientific partners. The Hothaps team welcomes independent use of the
      study protocols, but would be grateful for information about any planned, ongoing
      or completed studies of this type. Coordinated implementation of the protocols in
      multi-centre studies is also welcome. Eventually, the results of the Hothaps
      field studies will be used in global assessments of climate change-induced heat
      exposure increase in workplaces and its impacts on occupational health and
      productivity. These results will also be of value for the next assessment by the
      Intergovernmental Panel on Climate Change (IPCC) in 2013.

PMID- 20052426
TI  - Work-related heat stress concerns in automotive industries: a case study from
      Chennai, India.
AB  - BACKGROUND: Work-related heat stress assessments, the quantification of thermal
      loads and their physiological consequences have mostly been performed in non
      tropical developed country settings. In many developing countries (many of which
      are also tropical), limited attempts have been made to create detailed job
      exposure profiles for various sectors. We present here a case study from Chennai
      in southern India that illustrates the prevalence of work-related heat stress in
      multiple processes of automotive industries and the efficacy of relatively simple
      controls in reducing prevalence of the risk through longitudinal assessments.
      METHODS: We conducted workplace heat stress assessments in automotive and
      automotive parts manufacturing units according to the protocols recommended by
      NIOSH, USA. Sites for measurements included indoor locations with process
      generated heat exposure, indoor locations without direct process-generated heat
      exposure and outdoor locations. Nearly 400 measurements of heat stress were made
      over a four-year period at more than 100 locations within eight units involved
      with automotive or automotive parts manufacturing in greater Chennai metropolitan
      area. In addition, cross-sectional measurements were made in select processes of
      glass manufacturing and textiles to estimate relative prevalence of heat stress.
      RESULTS: Results indicate that many processes even in organised large-scale
      industries have yet to control heat stress-related hazards adequately. Upwards of
      28% of workers employed in multiple processes were at risk of heat stress-related
      health impairment in the sectors assessed. Implications of longitudinal baseline
      data for assessing efficacy of interventions as well as modelling potential
      future impacts from climate change (through contributions from worker health and
      productivity impairments consequent to increases in ambient temperature) are
      described. CONCLUSIONS: The study re-emphasises the need for recognising heat
      stress as an important occupational health risk in both formal and informal
      sectors in India. Making available good baseline data is critical for estimating
      future impacts.

PMID- 20052427
TI  - The thermal environment of the human being on the global scale.
AB  - BACKGROUND: The close relationship between human health, performance, well-being
      and the thermal environment is obvious. Nevertheless, most studies of climate and
      climate change impacts show amazing shortcomings in the assessment of the
      environment. Populations living in different climates have different
      susceptibilities, due to socio-economic reasons, and different customary
      behavioural adaptations. The global distribution of risks of hazardous thermal
      exposure has not been analysed before. OBJECTIVE: To produce maps of the baseline
      and future bioclimate that allows a direct comparison of the differences in the
      vulnerability of populations to thermal stress across the world. DESIGN: The
      required climatological data fields are obtained from climate simulations with
      the global General Circulation Model ECHAM4 in T106-resolution. For the thermo
      physiologically relevant assessment of these climate data a complete heat budget
      model of the human being, the 'Perceived Temperature' procedure has been applied
      which already comprises adaptation by clothing to a certain degree. Short-term
      physiological acclimatisation is considered via Health Related Assessment of the
      Thermal Environment. RESULTS: The global maps 1971-1980 (control run, assumed as
      baseline climate) show a pattern of thermal stress intensities as frequencies of
      heat. The heat load for people living in warm-humid climates is the highest.
      Climate change will lead to clear differences in health-related thermal stress
      between baseline climate and the future bioclimate 2041-2050 based on the
      'business-as-usual' greenhouse gas scenario IS92a. The majority of the world's
      population will be faced with more frequent and more intense heat strain in spite
      of an assumed level of acclimatisation. Further adaptation measures are crucial
      in order to reduce the vulnerability of the populations. CONCLUSIONS: This
      bioclimatology analysis provides a tool for various questions in climate and
      climate change impact research. Considerations of regional or local scale require
      climate simulations with higher resolution. As adaptation is the key term in
      understanding the role of climate/climate change for human health, performance
      and well-being, further research in this field is crucial.

PMID- 20052428
TI  - Using high spatial resolution remote sensing for risk mapping of malaria
      occurrence in the Nouna district, Burkina Faso.
AB  - INTRODUCTION: Malaria control measures such as early diagnosis and treatment,
      intermittent treatment of pregnant women, impregnated bed nets, indoor spraying
      and larval control measures are difficult to target specifically because of
      imprecise estimates of risk at a small-scale level. Ways of estimating local
      risks for malaria are therefore important. METHODS: A high-resolution satellite
      view from the SPOT 5 satellite during 2008 was used to generate a land cover
      classification in the malaria endemic lowland of North-Western Burkina Faso. For
      the area of a complete satellite view of 60 x 60 km, a supervised land cover
      classification was carried out. Ten classes were built and correlated to land
      cover types known for acting as Anopheles mosquito breeding sites. RESULTS:
      According to known correlations of Anopheles larvae presence and surface water
      related land cover, cultivated areas in the riverine vicinity of Kossi River were
      shown to be one of the most favourable sites for Anopheles production. Similar
      conditions prevail in the South of the study region, where clayey soils and
      higher precipitations benefit the occurrence of surface water. Besides pools,
      which are often directly detectable, rice fields and occasionally flooded crops
      represent most appropriate habitats. On the other hand, forests, elevated regions
      on porous soils, grasslands and the dryer, sandy soils in the north-western part
      turned out to deliver fewer mosquito breeding opportunities. CONCLUSIONS:
      Potential high and low risks for malaria at the village level can be
      differentiated from satellite data. While much remains to be done in terms of
      establishing correlations between remotely sensed risks and malaria disease
      patterns, this is a potentially useful approach which could lead to more focused
      disease control programmes.

PMID- 20052429
TI  - Milder winters in northern Scandinavia may contribute to larger outbreaks of
      haemorrhagic fever virus.
AB  - The spread of zoonotic infectious diseases may increase due to climate factors
      such as temperature, humidity and precipitation. This is also true for
      hantaviruses, which are globally spread haemorrhagic fever viruses carried by
      rodents. Hantaviruses are frequently transmitted to humans all over the world and
      regarded as emerging viral diseases. Climate variations affect the rodent
      reservoir populations and rodent population peaks coincide with increased number
      of human cases of hantavirus infections. In northern Sweden, a form of
      haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala
      hantavirus (PUUV) is endemic and during 2006-2007 an unexpected, sudden and large
      outbreak of NE occurred in this region. The incidence was 313 cases/100,000
      inhabitants in the most endemic areas, and from January through March 2007 the
      outbreak had a dramatic and sudden start with 474 cases in the endemic region
      alone. The PUUV rodent reservoir is bank voles and immediately before and during
      the peak of disease outbreak the affected regions experienced extreme climate
      conditions with a record-breaking warm winter, registering temperatures 6-9
      degrees C above normal. No protective snow cover was present before the outbreak
      and more bank voles than normal came in contact with humans inside or in close to
      human dwellings. These extreme climate conditions most probably affected the
      rodent reservoir and are important factors for the severity of the outbreak.

PMID- 20052430
TI  - A pilot field evaluation on heat stress in sugarcane workers in Costa Rica: What
      to do next?
AB  - BACKGROUND: Climate change is producing major impacts including increasing
      temperatures in tropical countries, like Costa Rica, where the sugarcane industry
      employs thousands of workers who are exposed to extreme heat. OBJECTIVES: This
      article outlines a pilot qualitative evaluation of working conditions and heat in
      the sugarcane industry. DESIGN: A literature review, direct observations and
      exploratory interviews with workers were conducted to reach a preliminary
      understanding of the dimensions of heat-related health issues in the sugarcane
      industry, as a basis for the design of future studies. RESULTS: The industry
      employs temporary workers from Nicaragua and Costa Rica as well as year-round
      employees. Temporary employees work 12-hour shifts during the harvest and
      processing ('zafra') season. In many cases, sugarcane field workers are required
      to carry their own water and often have no access to shade. Sugar mill workers
      are exposed to different levels of heat stress depending upon their job tasks,
      with the most intense heat and workload experienced by the oven ('caldera')
      cleaners. CONCLUSIONS: Research is needed to achieve better understanding of the
      multiple factors driving and interacting with heat exposures in the sugarcane
      industry in order to improve the health and safety of workers while maintaining
      worker productivity.

PMID- 20052431
TI  - Climate change influences infectious diseases both in the Arctic and the tropics:
      joining the dots.

PMID- 20052432
TI  - Effects of climate change on tularaemia disease activity in Sweden.
AB  - Tularaemia is a vector-borne infectious disease. A large majority of cases
      transmitted to humans by blood-feeding arthropods occur during the summer season
      and is linked to increased temperatures. Therefore, the effect of climate change
      is likely to have an effect on tularaemia transmission patterns in highly endemic
      areas of Sweden. In this report, we use simulated climate change scenario data
      and empirical data of temperatures critical to tularaemia transmission to
      forecast tularaemia outbreak activity. The five high-endemic counties: Dalarna,
      Gavleborg, Norrbotten, Varmland and Orebro represent only 14.6% of the total
      population of Sweden, but have recorded 40.1-81.1% of the number of annual human
      tularaemia in Sweden from 1997 until 2008. We project here earlier starts and a
      later termination of future tularaemia outbreaks for the time period 2010-2100.
      For five localised outbreak areas; Gagnef (Dalarna), Ljusdal (Gavleborg), Harads
      (Norrbotten), Karlstad (Varmland) and Orebro municipality (Orebro), the climate
      scenario suggests an approximately 2 degrees C increase in monthly average summer
      temperatures leading to increases in outbreak durations ranging from 3.5 weeks
      (Harads) to 6.6 weeks (Karlstad) between 2010 and 2100. In contrast, an analysis
      of precipitation scenarios indicates fairly stable projected levels of
      precipitation during the summer months. Thus, there should not be an increased
      abundance of late summer mosquitoes that are believed to be main vectors for
      transmission to humans in these areas. In conclusion, the results indicate that
      the future climate changes will lead to an increased burden of tularaemia in high
      endemic areas of Sweden during the coming decades.

PMID- 20052433
TI  - Using medical students as research subjects: is it ethical?

PMID- 20052434
TI  - Three I's and the future of medicine.

PMID- 20052435
TI  - Preparedness for terrorism: managing nuclear, biological and chemical threats.
AB  - The management of nuclear, biological and chemical (NBC) terrorism events is
      critical to reducing morbidity and mortality in the next decade; however, initial
      patient care considerations and protective actions for staff are unfamiliar to
      most front-line clinicians. High explosive events (bomb and blast) remain the
      most common type of terrorism and are easy to detect. Conversely, some types of
      terrorist attacks are more likely to be unsuspected or covert. This paper
      explains the current threat of terrorism and describes clues for detection that
      an event has occurred. Specific criteria that should lead to a high suspicion for
      terrorism are illustrated. The manuscript outlines initial actions and clinical
      priorities for management and treatment of patients exposed to
      nuclear/radiological, biological, chemical and combined agents (for example an
      explosion involving a chemical agent). Examples of terrorist events include: a
      nuclear explosion, an aerosolised release of anthrax (biological), dissemination
      of sarin in a subway (chemical), and the detonation of a radiologic dispersion
      device or "dirty bomb" (combined explosive and radiological). Basic principles of
      decontamination include potential risks to healthcare providers from secondary
      exposure and contamination. Unique issues may hinder clinical actions. These
      include coordination with law enforcement for a crime scene, public health
      entities for surveillance and monitoring, hazardous materials teams for
      decontamination, and the media for risk communications. Finally, the importance
      of personal preparedness is discussed.

PMID- 20052436
TI  - Radiology: does it have a sell-by date?
AB  - In a few years we are likely to see 3D images generated instantly, and with
      comparable resolution to today's 2D views. Inclusion of functional information,
      possibly at the molecular level, could also assist in clinical decision-making.
      Some specialist clinicians with intimate knowledge of their field of interest are
      likely to have a better understanding of the pathology and physiology of an organ
      system than a general radiologist. So given that the images will be presented in
      a more familiar format, why should clinicians and surgeons wait for a general
      radiologist to read them? If radiologists wish to retain their role as the
      experts in image interpretation, they will not only need a thorough understanding
      of imaging and radiological anatomy, but also a detailed understanding of
      pathology and physiology. It is clearly unrealistic to expect most people to gain
      that knowledge across a range of fields, hence the need for subspecialization.
      There are already commercial moves to harness the expertise of superspecialist
      radiologists, using teleradiology, to provide expert opinions in particularly
      difficult cases. This is just the beginning of a major shift in the pattern of
      practice in radiology. The radiology community cannot ignore impending
      technological developments. If radiologists take no interest in the emergence of
      highly detailed, user-friendly images, then the clinicians and surgeons will
      organise their own department-based image interpretation. However, radiologists
      are very good at adapting to technological change and are very likely to rise to
      these challenges. Far from having a sell-by date, radiology has a bright future.

PMID- 20052437
TI  - Surgical training - the challenge of change.
AB  - The healthcare environment is continuing to change and so too is education and
      training of surgeons. We now live in an age of increased specialisation, of
      technology, of accountability, of greater patient education and expectation and
      mass media attention. The traditional apprentice method and emphasis too much on
      examinations will have to be changed to a more structured system of training with
      training standards, regular assessment and feed back. There are new skills to be
      learnt for future surgical practice and new ways to learn them to become
      competent. We need to make changes in the institutions and departments to create
      a learning environment and an organisational system to implement the training
      programme. The current shortage of surgical work force in the institutions and
      lack of sufficient teachers committed to teaching and training are major issues
      that need to be addressed.

PMID- 20052438
TI  - Tumour interstitial fluid pressure may regulate angiogenic factors in
      osteosarcoma.
AB  - PURPOSE: We have previously shown that osteosarcomas have states of increased
      interstitial fluid pressure (IFP) which correlate with increased proliferation
      and chemosensitivity. In this study, we hypothesized that constitutively raised
      IFP in osteosarcomas regulates angiogenesis. MATERIALS AND METHODS: Sixteen
      patients with the clinical diagnosis of osteosarcomas underwent blood fl ow and
      IFP readings by the wick-in-needle method at the time and location of open
      biopsy. Vascularity was determined by capillary density in the biopsy specimens.
      We performed digital image analysis of immunohistochemical staining for CD31,
      VEGF-A, VEGF-C and TPA on paraffin-embedded tissue blocks of the biopsy samples.
      Clinical results were validated in a pressurised cell culture system. RESULTS:
      IFPs in the tumours (mean 33.5 +/- SD 17.2 mmHg) were significantly higher (P =
      0.00001) than that in normal tissue (2.9 +/- 5.7 mmHg). Pressure readings were
      significantly higher in low vascularity tumours compared to high vascularity
      tumours (P <0.001). In the osteosarcoma cell lines, growth in a pressurised
      environment was associated with VEGF-A downregulation, VEGF-C upregulation and
      TPA upregulation. The reverse was seen in the OB cell lines. Growth in the HUVEC
      cell line was not significantly inhibited in a pressurised environment.
      Immunohistochemical assessment for VEGF-A (P = 0.01), VEGF-C (P = 0.008) and TPA
      (P = 0.0001) translation were consistent with the findings on PCR. CONCLUSION:
      Our data suggest that some molecules in angiogenesis are regulated by changes in
      IFP.

PMID- 20052439
TI  - Lack of awareness amongst community patients with diabetes and diabetic
      retinopathy: the Singapore Malay eye study.
AB  - INTRODUCTION: We assessed awareness of diabetes and diabetic retinopathy in a
      Singaporean Malay population. We hypothesised that poor awareness is associated
      with poorer control of diabetic retinopathy risk factors (glycaemic and blood
      pressure levels) and suboptimal treatment with laser therapy. MATERIALS AND
      METHODS: A population-based survey of 3280 (78.7% response rate) persons among
      Singaporean Malays aged between 40 and 80 years old. Diabetes was defined in
      persons with random glucose >or=11.1mmoL/L, use of diabetic medication, or a
      previous physician diagnosis. Diabetic retinopathy was graded from retinal
      photographs following the modified Airlie House classification. Patient awareness
      was assessed via structured interviews. Glycosylated haemoglobin was measured
      from venous blood. RESULTS: Of the 3280 study participants, 768 had diabetes, of
      whom 13.2% (n = 101) were unaware of their diabetes status. Participants unaware
      of their diabetes status had significantly higher mean glycosylated haemoglobin
      (9.7% vs 8.2%, P <0.001), systolic blood pressure (160.0 mmHg vs 153.7 mmHg, P =
      0.01) and diastolic blood pressure (83.5 mmHg vs 78.5 mmHg, P <0.001), compared
      to participants who were aware. Of the 272 (35.4%) participants detected to have
      diabetic retinopathy, 83.4% (n = 227) were unaware of having retinopathy. Of the
      77 with vision-threatening retinopathy, laser treatment had been performed in
      only 55.6% of those unaware of having retinopathy. CONCLUSION: In a sample of
      Malays with diabetes, high proportions were unaware of their disease. Unawareness
      was associated with poorer control of diabetic retinopathy risk factors. Only
      half of persons who were unaware that they had vision-threatening diabetic
      retinopathy had received laser treatment. These data highlight room for
      improvement in diabetic retinopathy prevention through better patient education
      and screening.

PMID- 20052440
TI  - Prevalence of adolescent idiopathic scoliosis among female school children in
      Singapore.
AB  - INTRODUCTION: Screening for scoliosis started in Singapore schools in 1982 and is
      currently being done for both boys and girls, as part of the annual school-based
      health screening programme in all primary and secondary schools. The screening
      levels in the current protocol were based on the 1997 prevalence study by Wong et
      al. In the study, it appeared that there was a significant increase in prevalence
      rates between 9- and 11-year-old girls (i.e. between Primary 4 and Primary 6) but
      there was no data on the prevalence rates of scoliosis in 10-year-old girls
      (Primary 5) and in 12-year-old girls (Secondary 1). In order to decide on whether
      to make changes to the screening levels, a review was conducted to determine the
      prevalence of scoliosis among the 10-year-old girls (in Primary 5) and 12-year
      old girls (in Secondary 1). MATERIALS AND METHODS: A total of 93,626 female
      students, aged between 9 and 13 years old were screened. The study covered all of
      the 183 primary schools and only 83 of the 165 secondary schools due to a
      disruption of health screening in schools during the outbreak of SARS (severe
      acute respiratory syndrome). In mid-2003, schools in Singapore were closed
      because Singapore was one of the countries affected by SARS. Scoliosis screening
      was done for all female students in the Primary 4, 5 and 6 levels as well as in
      the Secondary 1 and 2 levels. Male students were routinely screened for scoliosis
      in the Primary 6 and Secondary 2 levels. Scoliosis screening was done by
      measuring the angle of trunk rotation (ATR) using a scoliometer. All students
      with ATR >or=5 degrees were referred to the Student Health Centre (SHC) where
      second-tier screening was done. At SHC, if ATR >or=5 degrees , postero-anterior
      radiograph of the spine was done. Of the 3186 female students in the primary
      level, aged between 9 and 13 years old who were referred to SHC for the second
      tier screening, 2438 attended, and for secondary students aged between 12 and 13
      years old, 1587 out of 1720 students attended. RESULTS: The prevalence rates of
      idiopathic adolescent scoliosis for the 9- to 13-year-old female students were
      0.27%, 0.64%, 1.58%, 2.22% and 2.49%, respectively, which showed an increasing
      trend in the prevalence rates with increasing age. There was a significant
      increase in the prevalence rates of adolescent idiopathic scoliosis (AIS) in the
      10- to 11-year-old females compared to the 9-year-old females (OR, 1.7; 95% CI,
      1.1-2.4; P = 0.010). There was also a significant increase in the prevalence
      rates in the 12- to 13-year-old females (OR, 2.2; 95% CI, 1.4-3.3; P = 0.001).
      CONCLUSIONS: The study showed a significant increase in the prevalence rates of
      scoliosis in the 10- to 11-year-old female students and again a significant
      increase in the prevalence rates in the 12- to 13-year-old female students. Since
      the prevalence rate for the 9-year-old females was quite low (0.27%), and there
      was a significant increase in the prevalence rates in the 10- to 11-year-old and
      12- to 13-year-old females, it was recommended that screening for females be
      performed every year commencing at 10 years old (Primary 5) until 13 years old
      (Secondary 2).

PMID- 20052441
TI  - Was it easy to use an Asthma Control Test (ACT) in different clinical practice
      settings in a tertiary hospital in Singapore?
AB  - INTRODUCTION: The Asthma Control Test (ACT) is a 5-item self-administered tool
      designed to assess asthma control. It is said to be simple, easy and can be
      administered quickly by patients in the clinical practice setting. This stated
      benefit has yet to be demonstrated in our local clinical practice setting. The
      aim was to identify factors associated with difficulty in the administration of
      the ACT in different clinical practice settings in a tertiary hospital in
      Singapore. MATERIALS AND METHODS: This is a prospective study performed from
      April to June 2008. All patients diagnosed with asthma and referred to an asthma
      nurse from the in-patient and out-patient clinical practice setting in Tan Tock
      Seng Hospital were enrolled. RESULTS: Four hundred and thirty-four patients were
      asked to complete the ACT tool. In the univariate model, we found that age,
      clinical setting and medical history to be significantly associated with the
      completion of the ACT. The odds of completion decreased by a factor of 0.92 (95%
      CI, 0.89 to 0.94) for every year's increase in age, and this was statistically
      significant (P <0.001). Similarly, the odds ratio of completion for those with
      more than 3 medical conditions by history were 0.59 (95% CI, 0.48 to 0.71) as
      compared to those with less than 3 medical conditions by history, and this was
      also significant (P <0.001). In the multivariate model, we only found age to be
      an independent and significant factor. After adjusting for age, none of the other
      variables initially significant in the univariate model remained significant.
      CONCLUSION: The results show that the ACT was simple and easy to be administered
      in younger-aged patients.

PMID- 20052442
TI  - Plasmid-mediated quinolone resistance determinants in urinary isolates of
      Escherichia coli and Klebsiella pneumoniae in a large Singapore hospital.
AB  - INTRODUCTION: At the time of the study, 3 plasmid-borne qnr determinants (qnrA,
      qnrB and qnrS) and 1 plasmid-borne aminoglycoside-modifying enzyme determinant
      that confers quinolone resistance (aac(6')-Ib-cr) had been described in the
      literature. MATERIALS AND METHODS: We studied the prevalence of the 3 qnr
      determinants in a total of 117 nalidixic acid-resistant urinary isolates of
      Klebsiella pneumoniae (61 isolates) and Escherichia coli (56 isolates) using
      multiplex polymerase chain reaction (PCR). Further, a subset of the original
      strains (comprising 14 E. coli and 38 K. pneumoniae) showing reduced
      susceptibility to the aminoglycosides underwent PCR for aac(6')-Ib, followed by
      restriction digestion with BtsCI to detect the variant aac(6')-Ib-cr. RESULTS:
      Twenty-eight of 61 (45.9%) Klebsiella isolates were found to possess at least 1
      qnr determinant. Only 1/56 (1.8%) E. coli isolates were found to possess a qnr
      determinant. Two of the Klebsiella isolates possessed 2 qnr determinants each
      (qnrB and qnrS). The predominant determinant was qnrB (19 isolates). There were
      11 isolates harbouring qnrS, and only 1 with qnrA. 1/14 (7.1%) E. coli and 35/38
      K. pneumoniae (92.1%) were found to possess aac(6')-Ib-cr. There was pairwise
      association between each of qnr, aac(6')-Ib-cr and the presence of an extended
      spectrum beta-lactamase. CONCLUSIONS: A high prevalence of plasmid-mediated
      quinolone resistance determinants [i.e., qnrS, qnrB and aac(6')-Ib-cr] was found
      in quinolone-resistant K. pneumoniae isolated in a large hospital in Singapore.

PMID- 20052443
TI  - Efficacy of an intravenous calcium gluconate infusion in controlling serum
      calcium after parathyroidectomy for secondary hyperparathyroidism.
AB  - INTRODUCTION: Intravenous calcium gluconate has been used to prevent
      postoperative hypocalcaemia (POH) following parathyroidectomy for secondary
      hyperparathyroidism in chronic kidney disease (CKD). MATERIALS AND METHODS:
      Retrospective data were obtained for 36 patients with CKD stage 4 and 5 after
      parathyroid surgery, correlating albumin-corrected serum calcium with the
      infusion rate of calcium gluconate. Calcium flux was characterised along with
      excursions out of the target calcium range of 2 to 3 mmol/L. With this data, an
      improved titration regimen was constructed. RESULTS: Mean peak efflux rate (PER)
      from the extracellular calcium pool was 2.97 mmol/h occurring 26.6 hours
      postoperatively. Peak calcium efflux tended to occur later in cases of severe
      POH. Eighty-one per cent of patients had excursions outside of the target calcium
      range of 2 to 3 mmol/L. Mean time of onset for hypocalcaemia was 2 days
      postoperatively. Hypocalcaemia was transient in 25% and persistent in 11% of
      patients. CONCLUSION: A simple titration regimen was constructed in which a 10%
      calcium gluconate infusion was started at 4.5 mL/h when serum calcium was <2
      mmol/L, then increased to 6.5 mL/h and finally to 9.0 mL/h if calcium continued
      falling. Preoperative oral calcium and calcitriol doses were maintained. Blood
      testing was done 6-hourly, but when a higher infusion rate was needed, 4-hourly
      blood testing was preferred. Monitoring was discontinued if no hypocalcaemia
      developed in the fi rst 4 days after surgery. If hypocalcaemia persisted 6 days
      after surgery, then the infusion was stopped with further monitoring for 24
      hours.

PMID- 20052444
TI  - The effect of temperature on illness severity in emergency department congestive
      heart failure patients.
AB  - INTRODUCTION: Previous studies revealed fewer visits for congestive heart failure
      (CHF) to emergency departments (EDs) in New Jersey, USA and fewer admissions for
      CHF to a Southern Indian and an Israeli hospital during warmer months. Using
      hospital admission rate for CHF as a marker for illness severity, we hypothesized
      that CHF would also be less severe in warmer months. MATERIALS AND METHODS: This
      is a retrospective cohort study which included all ED visits from 1 January 2004
      to 31 January 2006. We analysed the monthly CHF hospital admission rates. We a
      priori chose to compare the admission rates for the 4 warmest to the 4 coldest
      months. RESULTS: Of a total of 136,347 ED visits, 1083 (0.8%) were accounted for
      CHF. Hospital admission rate was 55.8%. Although there was a statistically
      significant increase in ED visits for CHF during the colder months, the 4 warmer
      months from June to September had 1.15 times higher hospital admission rate than
      the 4 coldest months from November to February. CONCLUSIONS: Contrary to our
      hypothesis, we found a statistically significant increase in the percentage of
      CHF visits admitted to the hospital during the warmer months. This suggests that
      although there are less ED CHF visits in the warmer months, a greater percentage
      tend to be severe.

PMID- 20052445
TI  - Three-year experience of primary percutaneous coronary intervention for acute ST
      segment elevation myocardial infarction in a hospital without on-site cardiac
      surgery.
AB  - INTRODUCTION: Primary percutaneous coronary intervention (PCI) for ST-segment
      elevation myocardial infarction (STEMI) in hospitals without on-site cardiac
      surgery capability, despite receiving only a class IIb recommendation in the
      ACC/AHA practice guidelines, can be performed effectively and safely. We reviewed
      the fi rst 3 years of our experience. MATERIALS AND METHODS: This is a
      retrospective single centre review of all patients receiving primary PCI for
      STEMI between 2003 and 2005. Demographic, procedural and outcome data were
      analysed. RESULTS: There were 259 patients who underwent primary PCI. The mean
      age was 55.3 +/- 12.3 years. Median door-to-balloon time was 97.5 minutes and
      45.2% and 52.9% had anterior and inferior STEMI, respectively. The majority of
      patients presented with Killip class I (87.6%); however, 5.8% were in Killip
      class IV. Single vessel disease was found in 47.1%. Angiographic PCI success
      (defined as residual stenosis <50% with TIMI 3 fl ow) was achieved in 89.1%.
      Usage of stents, distal protection and aspiration devices were 97.2%, 27.8% and
      34.1 %, respectively; 9.3% required intra-aortic balloon pump insertion. No
      patients required transfer for emergency coronary bypass surgery as a result of
      PCI complications. Post-PCI ST resolution >50% was achieved in 80.6%. The mean
      post-infarct left ventricular ejection fraction was 44.1%. In-hospital, 30-day, 6
      month and 1-year mortality rates were 2%, 2.8%, 4.0% and 4.8%, respectively.
      Clinically driven target lesion revascularisation rate was 2.8% at 1 year.
      CONCLUSIONS: Our results are comparable to those from on-site surgical centres.
      This supports the feasibility and safety of primary PCI in cardiac centres
      without on-site cardiac surgery.

PMID- 20052446
TI  - Infected non-union of the humerus after failure of surgical treatment: management
      using the Orthofix external fixator.
AB  - INTRODUCTION: The failure of a humeral fracture to unite after surgical treatment
      may be due to many factors. When there are additional complications of infection,
      treatment by conventional methods of internal fixation becomes very difficult.
      MATERIALS AND METHODS: We treated 8 infected non-union of diaphyseal fracture of
      the humerus by the Orthofix external fixator. All had previous surgical
      treatment. Non-union followed plating in 6 cases and in 2 cases after the
      external fixator. All patients had pain, at least one sinus discharging pus and
      severe functional impairment of the affected arm. There were 6 men and 2 women
      with a mean age 40.6 years. RESULTS: Bone union was achieved in all cases. The
      mean time to union was 4.5 months (range, 2 to 8). Patients expressed high levels
      of satisfaction with the outcome, despite relatively modest improvement in pain
      and function, mainly because of long standing infection and intractable non
      union. There were no major pin tract problems requiring the removal of the Schanz
      screws. Radial nerve palsy developed in 1 patient who recovered spontaneously. No
      patient required an additional bone grafting procedure. CONCLUSION: The use of
      the Orthofix external fixator without bone grafting was successful in the
      treatment of infected non-union of the humeral shaft. It shortened the duration
      of hospitalisation and immobilisation with moderate functional recovery.

PMID- 20052447
TI  - Drug use and dosing in chronic kidney disease.
AB  - One of the most important drug-related problems in patients with chronic kidney
      disease (CKD) is medication dosing errors. Many medications and their metabolites
      are eliminated through the kidney. Thus, adequate renal function is important to
      avoid toxicity. Patients with renal impairment often have alterations in their
      pharmacokinetic and pharmacodynamic parameters. The clearance of drugs eliminated
      primarily by renal filtration is decreased by renal disease. Therefore, special
      consideration should be taken when these drugs are prescribed to patients with
      impaired renal function. Despite the importance of dosage adjustment in patients
      with CKD, such adjustments are sometimes ignored. Physicians and pharmacists can
      work together to accomplish safe drug prescribing. This task can be complex and
      require a stepwise approach to ensure effectiveness, minimise further damage and
      prevent drug nephrotoxicity.

PMID- 20052448
TI  - Real-time monitoring of blood flow changes during intravenous thrombolysis for
      acute middle cerebral artery occlusion.

PMID- 20052449
TI  - Seroepidemiology of hepatitis B and hepatitis C virus infections in people
      receiving health checkups - a hospital-based study.

PMID- 20052450
TI  - Extensive cutaneous metastases from colonic adenocarcinoma.

PMID- 20052451
TI  - Paratracheal abscess: a near fatal complication.

PMID- 20052452
TI  - Pulmonary hamartoma.

PMID- 20052453
TI  - [Smoking prevention in schools. A model for success].
AB  - Because of compulsory education and, thus, accessibility to all school-age
      children, schools are especially good places for tobacco prevention measures. For
      integrated, successful tobacco prevention in schools, the combination of
      structural and behavioral topics is necessary ("policy mix"). The Federal Center
      for Health Education has placed emphasis on school-based smoking prevention at an
      early stage. Within the framework of the smoke-free campaign, the Federal Center
      for Health Education created manuals and concepts for pupils, teachers, and
      parents for nationwide use. Starting in 2003, model projects focusing on smoke
      free schools were started by the Federal Center for Health Education. Since 2008,
      all German federal states have signed smoking bans for schools into law.

PMID- 20052454
TI  - Oxidative stress and glucose metabolism--is there a need to revisit effects of
      insulin treatment?

PMID- 20052455
TI  - The effects of aerobic exercise on metabolic risk, insulin sensitivity and
      intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a
      randomised controlled trial.
AB  - AIMS/HYPOTHESIS: We sought to determine the effect of an aerobic exercise
      intervention on clustered metabolic risk and related outcomes in healthy older
      adults in a single-centre, explanatory randomised controlled trial. METHODS:
      Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly
      assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a
      non-intervention control group. Randomisation and group allocation were conducted
      by the study co-ordinator, using a software programme. Those with prevalent
      diabetes, unstable ischaemic heart disease or poor mobility were excluded. All
      data were collected at our clinical research facility in Cambridge. Components of
      the metabolic syndrome were used to derive a standardised composite metabolic
      risk score (zMS) as the primary outcome. Trial status: closed to follow-up.
      RESULTS: We randomised 100 participants (50 to the intervention, 50 to the
      control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of
      participants attended for follow-up measures. There were no serious adverse
      events. Using an intention-to-treat analysis, we saw a non-significant reduction
      in zMS in the exercise group compared with controls (0.07 [95% CI -0.03, 0.17], p
      = 0.19). However, the exercise group had significantly decreased weight, waist
      circumference and intrahepatic lipid, with increased aerobic fitness and a 68%
      reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11
      0.92], p = 0.035) compared with controls. Results were similar in per-protocol
      analyses. CONCLUSIONS/INTERPRETATION: Enrolment in a supervised aerobic exercise
      intervention led to weight loss, increased fitness and improvements in some but
      not all metabolic outcomes. In appropriately screened older individuals, such
      interventions appear to be safe. TRIAL REGISTRATION: Controlled-trials.com
      ISRCTN60986572 FUNDING: Medical Research Council.

PMID- 20052456
TI  - Noninvasive and invasive ventilation in acute respiratory failure associated with
      bronchiectasis.
AB  - PURPOSE: To describe the outcomes of patients with bronchiectasis and acute
      respiratory failure (ARF) treated with noninvasive ventilation (NIV) and invasive
      mechanical ventilation (IMV) after a failure of conservative measures, and to
      identify the predictors of hospital mortality and NIV failure. METHODS:
      Retrospective review of bronchiectatic patients on NIV (n = 31) or IMV (n = 26)
      for ARF over 8 years in a medical intensive care unit (ICU) experienced in NIV.
      RESULTS: At baseline, the NIV group had more patients with acute exacerbations
      without identified precipitating factors (87.1 vs. 34.6%, p < 0.001), higher pH
      (mean 7.25 vs. 7.18, p = 0.008) and PaO(2)/FiO(2) ratio (mean 249.4 vs. 173.2, p
      = 0.02), and a trend towards a lower APACHE II score (mean 25.3 vs. 28.4, p =
      0.07) than the IMV group. There was no difference in hospital mortality between
      the two groups (25.8 vs. 26.9%, p > 0.05). The NIV failure rate (need for
      intubation or death in the ICU) was 32.3%. Using logistic regression, the APACHE
      II score was the only predictor of hospital mortality (OR 1.19 per point), and
      the PaO(2)/FiO(2) ratio was the only predictor of NIV failure (OR 1.02 per mmHg
      decrease). CONCLUSIONS: The hospital mortality of patients with bronchiectasis
      and ARF approximates 25% and is predicted by the APACHE II score. When
      selectively applied, NIV fails in one-third of the patients, and this is
      predicted by hypoxemia. Our findings call for randomised controlled trials to
      compare NIV versus IMV in such patients.

PMID- 20052457
TI  - Factors affecting short-term precision of musculoskeletal measures using
      peripheral quantitative computed tomography (pQCT).
AB  - Few studies have investigated factors influencing the precision of peripheral
      quantitative computed tomography (pQCT) measures. This study found time between
      repeat scans and subject anthropometric characteristics to influence short-term
      precision of pQCT-derived measures in the lower leg. These findings have
      implications for both investigators and clinicians utilizing pQCT outcomes.
      INTRODUCTION: Peripheral quantitative computed tomography (pQCT) is increasingly
      being used to investigate musculoskeletal changes associated with age, disease
      and/or intervention. Precision of pQCT measures is of paramount importance in
      this endeavor. This study aimed to establish the short-term precision of pQCT
      derived musculoskeletal measures of the lower leg and investigate factors
      influencing this precision. METHODS: Thirty healthy subjects had a series of six
      pQCT scans of the lower leg (66% of tibial length proximal from its distal end)
      performed on two separate days by two different testers. The influences of
      different testers, time between repeat scans, and subject anthropometric
      characteristics on precision were explored. RESULTS: Overall precision error
      (root mean square) increased from bone (<1%) to muscle (<1.5%) to fat (3%). The
      two testers were equally precise in performing pQCT measures; however, precision
      error increased when repeat scans were repeated 1 week apart as opposed to on the
      same day. Subject anthropometric characteristics influenced precision errors with
      the general finding being that an increase in subject size was associated with
      less precise pQCT measures. CONCLUSIONS: pQCT is a relatively precise technique
      for the assessment of bone and muscle, but precision is influenced by time
      between repeat scans and subject anthropometric characteristics. Investigators
      and clinicians need to be aware of these factors influencing pQCT outcomes as
      they may influence statistical power in clinical studies and the characterization
      of change in individual patients.

PMID- 20052458
TI  - Anorexia nervosa, osteoporosis and circulating leptin: the missing link.
AB  - Methods: Leptin levels were measured in 103 consecutive women with anorexia
      nervosa. Results: Spine BMD and Z-score values were found to be significantly
      lower in the low tertile compared with the highest tertile. Duration of
      amenorrhea and leptin level accounted for 27% of the variance in lumbar spine
      BMD. INTRODUCTION: The purpose of this study was to assess leptin levels and
      other biological variables in a population of anorexia nervosa patients. METHODS:
      Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN)
      with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by
      dual energy X-ray absorptiometry (DXA). RESULTS: Spine bone mineral density (BMD)
      and Z-score values were found to be significantly lower in the low tertile
      compared with the highest tertile. Duration of amenorrhea and leptin level
      accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was
      3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin
      values was not a Gaussian distribution, and a log-transformed was therefore
      performed. A significant correlation was found between leptin level and spinal
      BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral
      neck and total hip BMDs. When leptin level values were divided into tertiles,
      spine BMD and Z-score values were found to be significantly lower in the lower
      tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral
      neck BMDs, the T-score was slightly lower between low and high tertile, but the
      difference was not statistically significant (p = 0.07). When multivariate
      analyses were performed, two independent factors which could possibly account for
      the variance in spinal BMDs were found. Duration of amenorrhea and leptin level
      accounted for 27% of the variance (p < 0.0001). CONCLUSION: The mechanisms
      underlying bone loss in AN patients remain unclear and complex, involving
      hypoestrogenia as well as nutritional factors such as insulin-like growth factor
      and leptin.

PMID- 20052459
TI  - Effects of sodium fluoride on hyperactivation and Ca2+ signaling pathway in sperm
      from mice: an in vivo study.
AB  - Sperm hyperactivation is crucial for a successful fertilization; however, the
      influence of fluoride (F) to hyperactivation is still in its infancy. The purpose
      of this study was to investigate the effect of sodium fluoride (NaF) on sperm
      hyperactivation, Ca2+/CALM-CAMK2 signaling, and CatSper1 and CatSper2 mRNA
      expression in mice sperm. Adult male Kunming mice were administrated with 30, 70,
      and 150 mg NaF/l (corresponding to 2.84 +/- 0.29, 6.28 +/- 0.61, and 14.18 +/-
      1.00 mg F/kg body weight per day) through drinking water for 49 days. The results
      showed that NaF reduced the sperm hyperactivated motility in a dose-dependent
      manner. Compared with the controls, intracellular Ca2+ concentration and CAMK2
      protein were significantly decreased in mice treated with 70 and 150 mg NaF/l,
      while no effect on CALM was determined in all treatment groups. Furthermore,
      decreased sperm CatSper1 mRNA expression was also observed in response to middle
      and higher doses of NaF (70, 150 mg/l) with comparison to the control group,
      whereas no change in the mRNA expression of CatSper2 was detected in NaF
      administrated groups. Treatment with 30 mg NaF/l exhibited slight effects on the
      above indexes with no statistical difference. These findings indicated that
      exposure to 70 and 150 mg/l NaF for 49 days could result in low hyperactivation
      via alteration of Ca2+ signaling pathway involving CatSper1 in sperm from mice.

PMID- 20052460
TI  - Scutellarin exerts its anti-hypertrophic effects via suppressing the Ca2+
      mediated calcineurin and CaMKII signaling pathways.
AB  - Scutellarin is a flavonoid extracted from a traditional Chinese herb, Erigeron
      breviscapus Hand Mazz, which has been broadly used in treating various
      cardiovascular diseases. In this study, we investigated its effect on cardiac
      hypertrophy and the underlying mechanism. Both in vitro and in vivo cardiac
      hypertrophy models were employed to explore the anti-hypertrophic action of
      scutellarin. We found that scutellarin significantly suppressed the hypertrophic
      growth of neonatal cardiac myocytes exposed to phenylephrine (PE) and mouse heart
      subjected to pressure overload induced by aortic banding, accompanied with the
      decreased expression of hypertrophic markers beta-myosin heavy chain and atrial
      natriuretic peptide. We then measured the change of free intracellular calcium
      using laser scanning confocal microscope. We found that scutellarin alleviated
      the increment of free intracellular calcium during cardiac hypertrophy either
      induced by PE or aortic banding. The expression of calcium downstream effectors
      calcineurin and phosphorylated calmodulin kinase II (CaMKII) were significantly
      suppressed by scutellarin. Our study indicated that scutellarin exerts its anti
      hypertrophic activity via suppressing the Ca(2+)-mediated calcineurin and CaMKII
      pathways, which supports the observation that clinical application of scutellarin
      is beneficial for cardiovascular disease patients.

PMID- 20052461
TI  - Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in
      patients following hip surgery--a pilot study.
AB  - The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors
      to avoid postoperative pain is an attractive option: they show favorable gastro
      intestinal tolerability, lack inhibition of blood coagulation, and carry a low
      risk of asthmatic attacks. The purpose of this study was to determine the
      cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally
      administered etoricoxib and to compare it with effect data, i.e., COX-2
      inhibition in patients after hip surgery. The study was performed in a blinded,
      randomized, parallel group design. A total of 12 adult patients were included who
      received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery.
      Samples from plasma, CSF, and tissue exudates were collected over a period of 24
      h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using
      liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF
      area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of
      the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to
      (50%) peak plasma concentration were </=2 h in all but one case (median: 1 h).
      PGE(2) production in tissue was significantly blocked by the COX-2 inhibitor
      starting with the appearance of etoricoxib in tissue and lasting for the whole
      observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF
      and site of surgery at effective concentrations and reduces PGE(2) production at
      the presumed site of action.

PMID- 20052462
TI  - Effect of calcium and pH on copper binding and rhizotoxicity to pea (Pisum
      sativum L.) root: Empirical relationships and modeling.
AB  - The accumulation and toxicity of Cu to pea (Pisum sativum L.) roots were
      investigated. The root uptake of Cu and Ca varied with Ca and H activities.
      Calcium, H, and Cu competed for root binding with high pH and low Ca favoring
      more Cu uptake. Root elongation was highly sensitive to root Ca content and
      correlated better with root-bound Ca and Cu content than with merely dissolved Cu
      concentrations. The prediction of root elongation needs to include both the root
      bond Cu and Ca as predictor variables whenever environmental conditions (low pH
      and low Ca) decrease Ca accumulation. A multielement uptake model was developed
      to describe Cu and Ca accumulation by treating the pea roots as a collection of
      three biotic ligands with known site densities (Q(L)(j)) and proton-binding
      constants (K(HL)(j)). A series of binding constants were derived. The log
      K(CuL)(j) (j = 1, 2, 3) values were estimated at pH 6 and 0.2 mM CaCl(2) as 2.36,
      4.36, and 0.32, respectively. The derived formation constants can be incorporated
      into standard solution speciation models to estimate the bioaccumulation of Cu in
      plant roots under multielement conditions.

PMID- 20052463
TI  - Fetal gastrointestinal MRI: all that glitters in T1 is not necessarily colon.
AB  - BACKGROUND: It has been described that both the colon and distal ileum present
      with a physiological hypersignal on T1-weighted sequences during the second and
      third trimesters of pregnancy because of their protein-rich meconium content, it
      was unclear whether the normal characteristics that have been described on fetal
      MRI can be applied to gastrointestinal (GI) obstructions. OBJECTIVE: To analyse
      the localisation value of T1 hypersignal within dilated bowel loops in fetuses
      with gastrointestinal tract obstruction. MATERIALS AND METHODS: A retrospective 4
      year multicentre study analysing cases of fetal GI obstruction in which MRI
      demonstrated T1 hypersignal content in the dilated loops. Data collected included
      gestational age (GA) at diagnosis, bowel appearance on US, CFTR gene mutations
      and amniotic levels of gastrointestinal enzymes. The suggested prenatal diagnosis
      was eventually compared to postnatal imaging and surgery. RESULTS: Eleven
      patients were included. The median GA at US diagnosis was 23 weeks (range 13-32).
      In eight cases there was a single dilated loop, while several segments were
      affected in three. The median GA at MRI was 29 weeks (range 23-35). One case
      presented with cystic fibrosis mutations. Final prenatally suspected diagnoses
      were distal ileal atresia or colon in nine cases and proximal atresia in two.
      Postnatal findings were proximal jejunal atresia in nine cases and meconium ileus
      in two. In five cases the surgical findings demonstrated short bowel syndrome.
      CONCLUSION: In cases of fetal occlusion, T1 hypersignal should not be considered
      as a sign of distal ileal or colonic occlusion. The obstruction may be proximal,
      implying a risk of small bowel syndrome, which requires adequate parental
      counselling.

PMID- 20052464
TI  - Diffusion-weighted imaging findings in Perthes disease with dynamic gadolinium
      enhanced subtracted (DGS) MR correlation: a preliminary study.
AB  - BACKGROUND: Legg-Calve-Perthes disease (LCP) is necrosis of the proximal femoral
      epiphysis of vascular origin. Clinical course and outcome in LCP disease varies
      considerably between different patients. Earlier prognostic criteria than those
      offered by conventional radiography are necessary to identify children who
      require prompt surgical treatment. OBJECTIVE: To assess the significance of
      signal alteration on diffusion-weighted MR imaging (DWI MR) in LCP. MATERIALS AND
      METHODS: Twelve boys with unilateral LCP disease (Catterall grade 2 and 3), at
      the initial sclerotic stage and early fragmentation phase, underwent dynamic
      gadolinium-enhanced subtracted (DGS) and DWI MR. For DGS MR, the lateral pillar
      enhancement was recorded. For DWI imaging, we measured ADC values in the diseased
      and the unaffected epiphyses and metaphyses. Receiver operating characteristic
      curves were performed to analyze the performance of DWI in establishing agreement
      with the results of DGS MR, which is the gold standard for prognosis. RESULTS:
      Femoral epiphysis increased diffusivity was observed in the affected hip in all
      cases. Increased metaphysis diffusivity in the affected side was observed in all
      cases with absent lateral pillar enhancement at DGS MR. CONCLUSION: DWI seems to
      be a noninvasive means of distinguishing between Perthes disease with favourable
      and unfavourable prognosis.

PMID- 20052465
TI  - Serum is not required for ex vivo IFN-gamma ELISPOT: a collaborative study of
      different protocols from the European CIMT Immunoguiding Program.
AB  - The Cancer Immunotherapy Immunoguiding Program has conducted an IFN-gamma ELISPOT
      proficiency panel to examine the influence of serum supplementation of test media
      on assay performance. Sixteen European laboratories analyzed the same PBMC
      samples using different locally established protocols. Participants generated two
      simultaneous data sets-one using medium supplemented with serum and one without
      serum. Performances of the two test conditions were compared by quantifying: (1)
      the number of viable cells, (2) background spot formation induced in the medium
      only control and (3) the ability to detect antigen-specific T cell responses. The
      study demonstrated that the number of viable cells recovered and the overall
      background spot production were not significantly different between the two
      conditions. Furthermore, overall laboratory performance was equivalent for the
      two test conditions; 11 out of 16 laboratories reported equal or greater
      detection rates using serum-free medium, while 5 laboratories reported decreased
      detections rates under serum-free conditions. These results show that good
      performance of the IFN-gamma ELISPOT assay can be achieved under serum-free
      conditions. Optimization of the protocol for serum-free conditions should result
      in excellent detection rates and eliminate the requirement of serum batch and
      stability testing, allowing further harmonization of the assay.

PMID- 20052466
TI  - CD34-based enrichment of genetically engineered human T cells for clinical use
      results in dramatically enhanced tumor targeting.
AB  - Objective clinical responses can be achieved in melanoma patients by infusion of
      T cell receptor (TCR) gene transduced T cells. Although promising, the therapy is
      still largely ineffective, as most patients did not benefit from treatment. That
      only a minority of the infused T cells were genetically modified and that these
      were extensively expanded ex vivo may have prevented their efficacy. We developed
      novel and generally applicable retroviral vectors that allow rapid and efficient
      selection of T cells transduced with human TCRs. These vectors encode two TCR
      chains and a truncated CD34 molecule (CD34t) in a single mRNA transcript.
      Transduced T cells were characterized and the effects of CD34-based enrichment of
      redirected T cells were evaluated. Both CD8(+) and CD4(+) T cells could be
      transduced and efficiently co-expressed all introduced transgenes on their
      surface. Importantly, more than fivefold enrichment of both the frequency of
      transduced cells and the specific anti-tumor reactivity of the effector
      population could be achieved by magnetic beads-based enrichment procedures
      readily available for clinical grade hematopoietic stem cell isolation. This CD34
      based enrichment technology will improve the feasibility of adoptive transfer of
      clinically relevant effectors. In addition to their enhanced tumor recognition,
      the enriched redirected T cells may also show superior reactivity and persistence
      in vivo due to the high purity of transduced cells and the shortened ex vivo
      culture.

PMID- 20052467
TI  - Papillary thyroid microcarcinoma: extrathyroidal extension, lymph node
      metastases, and risk factors for recurrence in a high prevalence of goiter area.
AB  - BACKGROUND: Although papillary thyroid microcarcinoma (PTMC) is diagnosed with
      increasing frequency, the best therapeutic option and follow-up protocol have not
      been established yet, especially in the case of incidental diagnosis. We reviewed
      our series of patients with PTMC to determine risk factors for recurrence in an
      area where there is a high prevalence of goiter. METHODS: The medical records of
      all patients who underwent thyroidectomy with a final pathology report of PTMC
      between October 2002 and June 2007 were reviewed. PTMC was defined as a papillary
      thyroid carcinoma 10 mm or less in diameter. Follow-up evaluation was obtained by
      outpatient consultation and/or telephone interview. RESULTS: In a series of 2,220
      patients who underwent thyroidectomy for a thyroid carcinoma, 933 had a PTMC.
      Diagnosis was incidental in 704 patients (75.5%). Upon multivariate analysis,
      tumor size, nonincidental diagnosis, and neck node metastases at diagnosis were
      independent risk factors for extracapsular spread (ECS), while ECS, multifocal
      disease, and number of removed lymph nodes were independent risk factors for
      lymph node metastases at diagnosis. Follow-up evaluation was completed in 287
      patients, 9 (3.1%) of whom experienced recurrence. The number of removed and
      metastasized nodes at first operation and the length of the follow-up were
      independent risk factors for recurrent disease. CONCLUSIONS: Incidental diagnosis
      of PTMC is frequent in a high prevalence of goiter area. PTMC shows a variable
      degree of aggressiveness. Management protocols should be based on patient- and
      tumor-related prognostic factors, as for larger tumors.

PMID- 20052468
TI  - Treatment of perforated diverticulitis with generalized peritonitis: past,
      present, and future.
AB  - BACKGROUND: The supposed optimal treatment of perforated diverticulitis with
      generalized peritonitis has changed several times during the last century, but at
      present is still unclear. METHODS/RESULTS: The first cases of complicated
      perforated diverticulitis of the colon were reported in the beginning of the
      twentieth century. At that time the first therapeutic guidelines were postulated
      in which an initial nonresectional procedure was provided to be the safest plan
      of management. After many years in which resection had become standard practice,
      today, one century later, again (laparoscopic) nonresectional surgery is
      presented as a safe and promising alternative in treatment of complicated
      perforated diverticulitis. The question rises what had happened to close the
      circle? CONCLUSIONS: This paper includes a historic summary of changing patterns
      in surgical strategies in perforated diverticulitis complicated by generalized
      peritonitis.

PMID- 20052469
TI  - The anatomy of lateral ligament of the rectum and its role in total mesorectal
      excision.
AB  - BACKGROUND: Lateral ligament of the rectum has suffered many diverse descriptions
      in its existence and composition. This study was undertaken to define the
      anatomy, nature, content of the lateral ligament of the rectum, and its role in
      total mesorectal excision. METHODS: Cadaver dissections were performed on 32
      formalin-preserved cadavers. RESULTS: Bilateral lateral ligament appeared in all
      32 cadavers as a bundle of dense connective tissue traversing between rectum and
      visceral fascia instead of pelvic sidewall. No substantial tissue strand except
      pelvic splanchnic nerves was found between visceral fascia and parietal fascia at
      the same level. The middle rectal artery was observed in only 18 of 64 pelvic
      halves (28.1%). The constant component of the lateral ligament of the rectum was
      the rectal branches from the pelvic plexus, whereas the middle rectal artery was
      almost invisible in lateral ligament of the rectum. CONCLUSIONS: During total
      mesorectal excision, it is impossible to reveal the lateral ligament of the
      rectum in the correct plane between visceral and parietal fascia. The entire
      rectum may be mobilized without the need for ligating the middle rectal artery.
      The clinical significance of lateral ligament is that, during lateral dissection,
      if the dense lateral ligament was identified, then the surgical plane was medial
      to the visceral fascia and incorrect surgical plane thus entered.

PMID- 20052470
TI  - Intraoperative determination of PTH concentrations in fine needle tissue
      aspirates to identify parathyroid tissue during parathyroidectomy.
AB  - BACKGROUND: Exact tissue identification during parathyroidectomy is essential to
      successfully cure hyperparathyroidism. PTH level determination from tissue
      aspirates has been advocated as a "biochemical frozen section" for parathyroid
      tissue identification. We investigated the sensitivity and specificity of this
      method in a large cohort of consecutive patients who underwent parathyroidectomy
      in a tertiary referral center. METHODS: PTH levels of 359 tissue aspirates were
      measured intraoperatively in 223 consecutive patients from March 2006 to December
      2008. Suspected parathyroid and control tissues were aspirated with a
      standardized technique immediately after their excision. Samples were processed
      for quick-PTH assay with peripheral blood samples before and after excision. PTH
      levels from tissue aspirates were correlated with pathological diagnosis. The
      Mann-Whitney test was used to determine statistical significance (P < 0.05).
      RESULTS: A total of 255 parathyroid (196 adenoma, 30 hyperplasia, 4 carcinoma, 25
      normal parathyroid) and 104 nonparathyroid tissue (88 thyroid, 16 lymph node,
      thymus, or fat) aspirates were compared. A highly significant difference was
      found between PTH levels of parathyroid (8,120 +/- 2,711 pg/ml; interquartile
      range (IQR): 4,949-9,075) and nonparathyroid (0.8 +/- 9.29 pg/ml; IQR: 0.4-1.4)
      tissue aspirates (P < 0.005). This test is 100% sensitive and 100% specific to
      identify parathyroid tissue for values >84 pg/ml. Furthermore, PTH levels of
      pathological parathyroid aspirates (8,169 +/- 2,597; IQR: 5,634-9,109) were
      higher than that of normal parathyroid aspirates (4,130 +/- 2,952; IQR: 2,569
      8,284; P = 0.0011). CONCLUSIONS: PTH level determination from tissue aspirates is
      a highly reliable, quick, and simple method to differentiate parathyroid and
      nonparathyroid tissues during parathyroidectomy. This method can obviate frozen
      sections in patients undergoing surgery for hyperparathyroidism.

PMID- 20052471
TI  - Lymph node ratio versus number of affected lymph nodes as predictors of survival
      for resected pancreatic adenocarcinoma.
AB  - BACKGROUND: The objective of this study was to compare the prognostic
      significance of the lymph node ratio (LNR) with the absolute number of affected
      lymph nodes for resected pancreatic ductal adenocarcinoma. METHODS: Data were
      collected from 84 patients who had undergone pancreatoduodenectomy for pancreatic
      ductal adenocarcinoma over a 10-year period. Patients were categorized into four
      groups according to the absolute LNR (0, 0-0.199, 0.2-0.299, > or =0.3). Kaplan
      Meier and Cox proportional hazard models were used to evaluate the prognostic
      effect. RESULTS: An LNR of > or =0.2 (median survival 8.1 vs. 35.7 months with
      LNR < 0.2; p < 0.001) and > or =0.3 (median survival 5.9 vs. 29.6 months with LNR
      < 0.3; p < 0.001), tumor size (p < 0.017), positive resection margin (p < 0.001),
      and nodal involvement (p < 0.001) were found to be significant prognostic markers
      following univariate analysis. Following multivariate analysis, only LNR at both
      levels [> or =0.2 (p = 0.05; HR 1.8) and LNR of > or =0.3 (p = 0.01; HR 2.7)]
      were independent predictors of a poor outcome. The number of lymph nodes examined
      had no effect on overall survival in either node-positive patients (p = 0.339) or
      node-negative patients (p = 0.473). CONCLUSIONS: The LNR represents a stronger
      independent prognostic indicator than the absolute number of affected lymph nodes
      in patients with resected pancreatic ductal adenocarcinoma.

PMID- 20052473
TI  - Syl611, a novel semisynthetic taxane derivative, reverses multidrug resistance by
      p-glycoprotein inhibition and facilitating inward transmembrane action.
AB  - PURPOSE: To investigate the reversal mechanisms of a novel semisynthetic taxane
      derivative, Syl611. Syl611 is a structurally modified compound from Sinenxan A,
      and the chemical structure is entirely new. It was found to significantly
      increase paclitaxel-induced cytotoxicity in drug-resistant cells, while
      presenting a low level of cytotoxicity. METHODS: The in vitro cytotoxic and MDR
      reversing activities of the Syl611 were determined by MTT assays. The
      cytotoxicity enhancement of paclitaxel was performed using the acridine
      orange/ethidium bromide double staining. Rhodamine 123 accumulation and retention
      assay in KB/V cells, Caco-2 monolayer model were used to find mechanism of
      action. RESULTS: The cytotoxicity of Syl611 was wondrously lower in all tested
      cell lines than that of paclitaxel. Cytotoxicity enhancement from Syl611 was
      dramatically higher than that of verapamil of the same concentration (10 muM):
      the reversal fold index for A549/Paclitaxel, KB/V, and Bel7402/5-FU were 45.95,
      73.56, and 107.13 (Syl611) and 11.36, 23.92, and 70.42 (verapamil). AO/EB double
      staining assay equally showed that Syl611 could enhance the cytotoxicity induced
      by paclitaxel. Furthermore, Syl611 could also increase the intracellular
      accumulation of Rhodamine 123 in KB/V cells without affecting P-gp's expression,
      and this accumulation was reversible. In bidirectional permeability assay, Syl611
      increased the permeability of paclitaxel but decreased the net secretory of
      paclitaxel. CONCLUSIONS: Syl611 is an effective and potential agent in reversing
      multidrug resistance (MDR) by multiple actions, which attributed to p
      glycoprotein inhibition and drug permeability enhancement.

PMID- 20052472
TI  - A modular Phase I study of lenalidomide and paclitaxel in metastatic castration
      resistant prostate cancer following prior taxane therapy.
AB  - PURPOSE: Lenalidomide, a highly potent immunomodulatory derivative of
      thalidomide, potentiates the action of paclitaxel in vitro against prostate
      cancer cell lines in co-culture with mononuclear cells. A modular Phase I study
      of lenalidomide and paclitaxel in men with metastatic castration-resistant
      prostate cancer (CRPC) was conducted to assess PSA kinetics with lead-in
      lenalidomide and the feasibility of the combination. METHODS: Men with metastatic
      CRPC with prior taxane chemotherapy were planned for single-agent "lead-in"
      lenalidomide for 21/28 days at dose-levels: -1 (5 mg), 0 (10 mg), +1 (15 mg), +2
      (20 mg), +3 (25 mg); followed by lenalidomide at the same dose and schedule in
      combination with weekly intravenous paclitaxel 100 mg/m(2) over 3 h on days 1, 8,
      15 every 28 days utilizing a 3 + 3 dose-escalation design. RESULTS: Dose-limiting
      toxicity was observed in 4/6 patients with first-cycle combination therapy at the
      10 mg dose-level and 3/6 patients at the 5 mg dose-level of lenalidomide,
      respectively. These included Grade 3 neutropenia precluding planned paclitaxel
      therapy (n = 3), grade 3 gastrointestinal toxicity (n = 2), chest pain (n = 1)
      and pulmonary embolism (n = 1). With lead-in lenalidomide, two patients with
      lymph-node dominant CRPC had a PSA-decline and regression in lymph node disease,
      respectively. Two of seven evaluable patients had PSA declines by 50% with
      combination therapy. Progression-free survival was 13 weeks (range 4-35 weeks).
      CONCLUSIONS: The high dose-limiting toxicity rates observed with lenalidomide and
      weekly paclitaxel require exploration of alternate dose-schedules of the
      combination in the second-line setting of CRPC. These early observations suggest
      distinctive toxicity and efficacy outcomes from thalidomide in combination with
      paclitaxel.

PMID- 20052474
TI  - Goldbeter-Koshland model for open signaling cascades: a mathematical study.
AB  - A modified Goldbeter-Koshland (GK) type model is proposed to study the open
      signaling cascade with forward activation. Three different regimes related to the
      ultrasensitivity are clearly defined. When the cascade is sufficiently long, the
      steady states in the downstream cycles exhibit a limiting behavior. Meanwhile, a
      temporal switch-like behavior is revealed in the pre-ultrasensitivity regime
      without any feedback circuitry. A detailed analysis of this phenomenon is
      provided.

PMID- 20052475
TI  - Ulnar nerve compression possibly due to aberrant veins: sonography is elucidatory
      for idiopathic cubital tunnel syndrome.

PMID- 20052476
TI  - Altered cytokine profiles of mononuclear cells after stimulation in a patient
      with Blau syndrome.
AB  - Autoinflammatory Blau syndrome (BS) is associated with NOD2 gene mutations that
      lead to constitutive NFkappaB activation. NOD2 functions as an intracellular
      receptor for the muramyl dipeptide (MDP) component of peptidoglycan (PGN). The
      objectives of this study are to analyse whether NFkappaB activation in BS affects
      immune cell functions, and whether NOD2 and toll-like receptor (TLR) pathways
      interact. Peripheral blood mononuclear cells (MNCs) from a BS patient and three
      normal donors were analyzed for their ability to produce pro- and anti
      inflammatory cytokines in the presence and absence of MDP, PGN, and
      lipopolysaccharide (LPS). The results obtained showed that the basal TNF-alpha
      and IL-10 production by MNCs over 24 h of incubation was very low for both the
      patient and the normal donors. However, upon stimulation with MDP, LPS, and PGN,
      the cells from the BS patient produced much lower levels of TNF-alpha, IL-10, G
      CSF, and IFN-gamma than the normal donor cells. We conclude that the pathogenic
      mechanism responsible for the chronic inflammation that characterizes BS may
      relate to the impaired production of both pro- and anti-inflammatory cytokines to
      stimuli. The NOD2 pathway possibly interacts with either the TLR2 or TLR4
      pathways.

PMID- 20052477
TI  - Empty sella syndrome presented with arthritis.

PMID- 20052478
TI  - Elevation of serum IgG subclass concentration in patients with rheumatoid
      arthritis.
AB  - A new concept of IgG subclass such as IgG4-related systemic disease including
      autoimmune pancreatitis, characterized by a high-serum IgG4 level, has been
      proposed. Our aim was to investigate serum IgG subclass levels in rheumatoid
      arthritis (RA). IgG subclass levels of sera from 72 patients with rheumatoid
      arthritis were determined by immunonephelometric assay. The patients were divided
      into two groups according to clinical activity of the disease: active disease and
      remission. The sera from 45 normal controls were also measured. All statistical
      analyses were carried out with SPSS software version 13.0. We found a significant
      increase of all the four IgG subclass concentrations in sera of patients with RA
      compared to those of the controls (P < 0.001). When the patients were divided
      according to clinical activity, the IgG subclass concentrations were similar
      between the two groups (P > 0.05). Our data suggest that besides IgG1, IgG2 and
      IgG3, IgG4 may involve in the pathogenesis of the disease.

PMID- 20052479
TI  - Natriuretic peptides in the detection of preclinical diastolic or systolic
      dysfunction.
AB  - AIMS: The diagnostic value of natriuretic peptides in asymptomatic patients at
      risk for diastolic or systolic HF is controversial. We tested (1) the prevalence
      of preclinical LV dysfunction in an at-risk cohort; (2) the diagnostic accuracy
      of natriuretic peptides alone or in combination with clinical parameters for
      predicting asymptomatic left ventricular systolic or diastolic dysfunction.
      METHODS: 542 primary care patients (mean age 63 +/- 11 years, 42% female) without
      prediagnosed HF, but with risk factors for left ventricular dysfunction,
      underwent thorough cardiological workup, including echocardiography and analysis
      of natriuretic peptides. RESULTS: 23 patients (4%) showed reduced systolic
      function (EF < 50%), and 15 patients (3%) had severe diastolic dysfunction. All
      natriuretic peptides significantly increased with decreasing ejection fraction
      and with increasing degree of diastolic dysfunction. For natriuretic peptides,
      receiver operating characteristics analysis yielded good results for the
      detection of systolic dysfunction or severe diastolic dysfunction. Combining
      clinical parameters with natriuretic peptide data improved the diagnostic
      accuracy and largely reduced the number of needed screening echoes to identify
      patients with LV systolic or diastolic dysfunction. CONCLUSIONS: The prevalence
      of preclinical diastolic dysfunction is high in primary care patients at risk,
      but the relative prevalence of severe diastolic dysfunction and systolic
      dysfunction is only 7%. High-risk individuals may be screened most efficiently by
      using a score system incorporating clinical data and NT-proBNP.

PMID- 20052480
TI  - Treatment of small coronary arteries with a paclitaxel-coated balloon catheter.
AB  - BACKGROUND: Treatment of lesions in small coronary arteries by percutaneous
      transluminal coronary intervention is limited by a high recurrence rate. We
      assessed the use of a paclitaxel-coated balloon in this indication. METHODS: One
      hundred eighteen patients with stenoses in small coronary vessels were treated by
      a paclitaxel-coated balloon (3 microg/mm(2)). The main inclusion criteria
      encompassed diameter stenosis of > or =70% and < or =22 mm in length with a
      vessel diameter of 2.25-2.8 mm. Follow-up angiography was performed at scheduled
      6-month post-intervention or whenever driven by clinical or electrocardiographic
      signs of ischemia. The primary endpoint was angiographic in-segment late lumen
      loss. RESULTS: Eighty-two of 118 patients (70%) with a vessel diameter of 2.35 +/
      0.19 mm were treated with the drug-coated balloon only, while 32 patients
      required additional stent deployment. The mean in-segment late lumen loss was
      0.28 +/- 0.53 mm. In patients treated with the drug-coated balloon only, the in
      segment late lumen loss was 0.16 +/- 0.38 mm. At 12 months, the rate of major
      adverse cardiac events was 15% which was primarily due to the need for target
      lesion revascularization in 14 patients (12%). In those with additional bare
      metal stent implantation geographical mismatch between coated-balloon dilatation
      and stent implantation was significantly associated with the occurrence of
      restenosis. CONCLUSION: Treatment of coronary stenosis in small coronary vessels
      with the paclitaxel-coated balloon was well tolerated. It may offer an
      alternative to the implantation of a drug-eluting stent (ClinicalTrials.gov
      Identifier: NCT00404144).

PMID- 20052481
TI  - Recombinant prion protein induces a new transmissible prion disease in wild-type
      animals.
AB  - Prion disease is a neurodegenerative malady, which is believed to be transmitted
      via a prion protein in its abnormal conformation (PrP(Sc)). Previous studies have
      failed to demonstrate that prion disease could be induced in wild-type animals
      using recombinant prion protein (rPrP) produced in Escherichia coli. Here, we
      report that prion infectivity was generated in Syrian hamsters after inoculating
      full-length rPrP that had been converted into the cross-beta-sheet amyloid form
      and subjected to annealing. Serial transmission gave rise to a disease phenotype
      with highly unique clinical and neuropathological features. Among them were the
      deposition of large PrP(Sc) plaques in subpial and subependymal areas in brain
      and spinal cord, very minor lesioning of the hippocampus and cerebellum, and a
      very slow progression of disease after onset of clinical signs despite the
      accumulation of large amounts of PrP(Sc) in the brain. The length of the clinical
      duration is more typical of human and large animal prion diseases, than those of
      rodents. Our studies establish that transmissible prion disease can be induced in
      wild-type animals by inoculation of rPrP and introduce a valuable new model of
      prion diseases.

PMID- 20052482
TI  - Inhibin/activin-betaE subunit is expressed in normal and pathological human
      placental tissue including chorionic carcinoma cell lines.
AB  - BACKGROUND: Inhibins and activins are important regulators of the female
      reproductive system. Recently, a novel inhibin subunit, named betaE, has been
      identified and shown to be expressed in several human tissues. However, only
      limited data on the expression of this novel inhibin-betaE subunit in normal and
      pathological human placenta as well as and human chorionic carcinoma cell lines
      exist. MATERIALS AND METHODS: Tissue specimens of normal, preeclamptic and HELLP
      pregnancies (n = 18) were obtained at the course of an cesarean section. Normal
      and pathological placental tissues as well as chorionic carcinoma cells (BeWo and
      JEG) were analyzed by using immunohistochemistry and RT-PCR. RESULTS: Expression
      of the inhibin betaE subunit could be demonstrated at the protein level by means
      of immunohistochemical evaluation and at the transcriptional level by betaE
      specific RT-PCR analysis. The immunoreactive score for inhibin-betaE did not show
      any significant differences between normal, preeclamptic and HELLP tissue in
      extravillous trophoblast and syncytiotrophoblast cells. Expression of inhibin
      betaE could further be demonstrated for the human chorionic carcinoma cell lines
      JEG and BeWo. DISCUSSION: We demonstrated that inhibin-betaE is expressed in
      normal and pathological human placenta tissues. Although the precise role of this
      novel inhibin subunit for human placenta development is quite unclear,
      similarities with the well-characterized betaA- and betaB-subunits suggest an
      involvement in autocrine/paracrine signaling pathways, angiogenesis,
      decidualization and tissue remodeling under normal as well as malignant
      conditions. Additionally, the human chorionic carcinoma cell lines JEG and BeWo
      synthesize this subunit and therefore can be used as a cell culture model for
      further functional analysis of this subunit in human placental tissue.

PMID- 20052483
TI  - The role of fetal autopsy and placental examination in the causes of fetal death:
      a retrospective study of 132 cases of stillbirths.
AB  - PURPOSE: To investigate the most plausible cause of stillbirth by evaluating
      clinical records and postmortem examination findings including placental
      analysis. METHODS: A retrospective cohort study concerning 132 stillbirths from
      124 pregnancies occurred in the Mother-Infant Department of the University
      Hospital of Modena, Italy, from January 2000 to December 2004. Collected data
      were reviewed and classified according to the Gardosi ReCoDe system. RESULTS: A
      reasonable cause of fetal death was identified in 99/124 pregnancies (79.84%). No
      associated relevant factors were disclosed in 25 fetuses (20.16%) classified as
      unexplained stillbirths. A succeeding scrupulous analysis of the placenta and an
      accurate clinical record review were useful to detect other conditions in 82
      cases, including 5 cases of unexplained stillbirth. The major relevant conditions
      associated to stillbirths were feto-placental infection especially in the early
      fetal gestation age, under the 24th week of gestation, and placental
      insufficiency occurred both in early and late gestation age fetuses and mainly
      associated with a IUGR (<10th customized percentile). The main frequent secondary
      conditions were represented by placental anomalies including cluster of avascular
      villi with stromal fibrosis associated to thrombosis in minor and/or major
      vessel(s). Through the further analysis of the placenta, we were able to reduce
      the unexplained stillbirth rate from 20.16 to 15%. CONCLUSION: Accurate fetal
      autopsy and placental examination related to meticulous clinical collecting data
      are requisites in the valuation of stillbirth and could play an important role in
      reduction of unexplained stillbirth rate.

PMID- 20052484
TI  - JCV detection in multiple sclerosis patients treated with natalizumab.
AB  - Natalizumab therapy is associated with an increased risk of progressive
      multifocal leukoencephalopathy (PML). Because the prognosis of established PML is
      uniformly dismal, identification of highly susceptible patients to the disease
      may improve outcomes. We wanted to investigate whether serial plasma and
      cerebrospinal fluid (CSF) screening for polyomavirus would identify patients with
      laboratory evidence of viral infection prior to the development of clinical PML.
      Two hundred MS patients had pre-treatment CSF/plasma screening for JC virus (JCV)
      and BK virus (BKV) DNA, and thereafter every six treatments of natalizumab. In
      all positive patients treatment is stopped (due to potential risk of PML), they
      have follow-up clinical examinations and plasma/CSF JCV/BKV tests until all
      evaluations are normal. No patient developed clinical evidence of PML. Eight of
      the 200 patients had detectable JCV or BKV DNA. Five patients were positive for
      BKV DNA in the CSF and three patients were positive for JCV DNA (one in plasma,
      two in CSF). After cessation of natalizumab treatment, all patients converted to
      undetectable viral DNA. Screening for JCV in CSF in natalizumab-treated patients
      could help identify those at heightened risk for developing PML and discontinuing
      treatment in these patients may abort development of the clinical illness.

PMID- 20052485
TI  - Rewarding and unrewarding aspects of deployment to Iraq and its association with
      psychological health in UK military personnel.
AB  - PURPOSE: Research into how individuals perceive their deployment experiences is
      important for understanding the association between stressful events and
      subsequent positive or negative effects. This study examines perceptions among UK
      military personnel with regard to rewarding and unrewarding aspects of deployment
      in Iraq. METHODS: Analyses were carried out on 5,573 UK military personnel who
      had deployed to Iraq between 2003 and 2006. Information on socio-demographic and
      military characteristics; deployment experiences, including perceptions of
      rewarding and unrewarding aspects of service; and information on current health,
      were collected with questionnaires. Associations between deployment and health
      factors, and participants' perceptions of service were examined. RESULTS: The
      rewarding aspects of deployment were related to military tasks such as "doing the
      job you were trained to do", "teamwork/comradeship" and altruistic aspects such
      as "helping local people". The unrewarding aspects were "being separated from
      family and friends" and "quality of supply and equipment". Although there was
      general agreement on the aspects that mattered to most Service personnel, there
      were differences associated with operation deployed to, enlistment type, rank,
      service and psychological health. Those with a psychological problem were more
      likely to find most military aspects of deployment unrewarding but were more
      likely to find helping the local population and working with other coalition
      forces rewarding. CONCLUSIONS: This study demonstrates how the perceptions of
      deployment, in terms of rewarding and unrewarding aspects, are shaped by service
      characteristics, mental health and operation deployed to.

PMID- 20052486
TI  - An evolutionarily conserved Myostatin proximal promoter/enhancer confers basal
      levels of transcription and spatial specificity in vivo.
AB  - Myostatin (Mstn) is a negative regulator of skeletal muscle mass, and Mstn
      mutations are responsible for the double muscling phenotype observed in many
      animal species. Moreover, Mstn is a positive regulator of adult muscle stem cell
      (satellite cell) quiescence, and hence, Mstn is being targeted in therapeutic
      approaches to muscle diseases. In order to better understand the mechanisms
      underlying Mstn regulation, we searched for the gene's proximal enhancer and
      promoter elements, using an evolutionary approach. We identified a 260-bp-long,
      evolutionary conserved region upstream of tetrapod Mstn and teleost mstn b genes.
      This region contains binding sites for TATA binding protein, Meis1, NF-Y, and for
      CREB family members, suggesting the involvement of cAMP in Myostatin regulation.
      The conserved fragment was able to drive reporter gene expression in C2C12 cells
      in vitro and in chicken somites in vivo; both normally express Mstn. In contrast,
      the reporter construct remained silent in the avian neural tube that normally
      does not express Mstn. This suggests that the identified element serves as a
      minimal promoter, harboring some spatial specificity. Finally, using
      bioinformatic approaches, we identified additional genes in the human genome
      associated with sequences similar to the Mstn proximal promoter/enhancer. Among
      them are genes important for myogenesis. This suggests that Mstn and these genes
      may form a synexpression group, regulated by a common signaling pathway.

PMID- 20052487
TI  - Presence of Borrelia burgdorferi in endomyocardial biopsies in patients with new
      onset unexplained dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) represents the third most common cause of heart
      failure and the most frequent cause of heart transplantation. Infectious, mostly
      viral, and autoimmune mechanisms, together with genetic abnormalities, have been
      reported as three major causes of DCM. We hypothesized that Lyme disease (LD),
      caused by spirochete Borrelia burgdorferi (Bb), might be an important cause of
      new-onset unexplained DCM in patients living in a highly endemic area for LD such
      as the Czech Republic. We performed endomyocardial biopsy (EMB) in 39 consecutive
      patients presenting with symptomatic unexplained left ventricular (LV) systolic
      dysfunction lasting no more than 12 months. In eight subjects (21%), Bb was
      detected in the EMB sample by polymerase chain reaction or by electron
      microscopy. None of these patients exhibited any form of atrioventricular block
      or other extracardiac manifestation of Bb infection. Serological testing
      identified IgG antibodies against Bb in only two cases and IgM antibodies in
      none. All affected patients were treated with intravenous ceftriaxone for 3
      weeks. At 6 months follow-up, LV morphology and function as well as functional
      status of these patients significantly improved. In conclusion, Bb infection may
      represent an important cause of new-onset unexplained DCM in patients living in
      endemic regions such as the Czech Republic. Because the antibiotic treatment
      appears to be markedly effective and serological examination does not provide a
      tool for diagnosing the disease, EMB focused on the detection of Bb should be
      performed in all patients from endemic areas with new-onset unexplained DCM not
      responding to conventional therapy.

PMID- 20052488
TI  - The epidemiology of hospitalized children with pneumococcal/lobar pneumonia and
      empyema from 1997 to 2004 in Taiwan.
AB  - Pneumococcal/lobar pneumonia and empyema have an important impact on the health
      of children worldwide. There has been no epidemiological study of
      pneumococcal/lobar pneumonia and empyema in Taiwan, a middle-income Asian
      population. Using Taiwan's National Health Insurance database, we collected and
      analyzed data obtain from medical care claims related to pneumococcal/lobar
      pneumonia and empyema for children below the 18 years old from 1997 to 2004. We
      found the annual population-based incidence to have significant year to year
      increases and the average annual incidences of pneumococcal/lobar pneumonia and
      empyema in children under five to be 44.9 and 10.5 episodes per 100,000 children
      year, respectively. About 64% of children with pneumococcal/lobar pneumonia and
      empyema were under 5 years old. Children 4 to 5 years old had the highest
      incidences of both pneumococcal/lobar pneumonia and empyema. Incidence was the
      highest each spring. The odds ratio of the case fatality among pneumococcal/lobar
      pneumonia patients complicated with empyema to those without was 118 (95%
      confidence interval 28-492). In conclusion, the population-based incidences of
      pneumococcal/lobar pneumonia and empyema among children under five in Taiwan were
      44.9 and 10.5 episodes per 100,000 children-year, respectively, and 4- to 5-year
      old children had the highest incidences of both pneumococcal/lobar pneumonia and
      empyema. This population might benefit from a universal pneumococcal vaccination
      program which might cover about 70% of invasive pneumococcal diseases in
      Taiwanese children under 5 years old.

PMID- 20052489
TI  - Analysis of the question-answer service of the Emma Children's Hospital
      information centre.
AB  - The information centre of the Emma Children's Hospital AMC (EKZ AMC) is a
      specialised information centre where paediatric patients and persons involved
      with the patient can ask questions about all aspects of disease and its social
      implications. The aim of the study was to evaluate the question-answer service of
      this information centre in order to determine the role of a specialised
      information centre in an academic children's hospital, identify the appropriate
      resources for the service and potential positive effects. For this purpose, a
      case management system was developed in MS ACCESS. The characteristics of the
      requester and the question, the time it took to answer questions, the information
      sources used and the extent to which we were able to answer the questions were
      registered. The costs of the service were determined. We analysed all questions
      that were asked in the year 2007. Fourteen hundred thirty-four questions were
      asked. Most questions were asked by parents (23.3%), healthcare workers (other
      than nurses; 16.5%) and nurses (15.3%). The scope of the most frequently asked
      questions include disease (20.2%) and treatment (13.0%). Information on paper was
      the main information source used. Most questions could be solved within 15 min.
      Twelve percent to 28% of total working hours are used for the question-answer
      service. Total costs including staff salary are rather large. In conclusions,
      taking over the task of providing additional medical information and by providing
      readily available, good quality information that healthcare professionals can use
      to inform their patients will lead to less time investment of these more
      expensive staff members. A specialised information service can anticipate on the
      information need of parents and persons involved with the paediatric patient. It
      improves information by providing with relatively simple resources that has the
      potential to improve patient and parent satisfaction, coping and medical results.
      A specialised information centre is therefore a valuable and affordable asset to
      an academic children's hospital.

PMID- 20052490
TI  - Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation
      showing DiGeorge sequence including hypoparathyroidism.
AB  - It is rare that coloboma, heart anomalies, choanal atresia, retarded growth and
      development, and genital and ear anomalies (CHARGE) syndrome patients have
      DiGeorge sequence showing severe immunodeficiency due to the defect of the
      thymus. Although the only treatment to achieve immunological recovery for these
      patients in countries where thymic transplantation is not ethically approved
      would be hematopoietic cell transplantation, long-term survival has not been
      obtained in most patients. On the other hand, it is still not clarified whether
      hypoparathyroidism is one of the manifestations of CHARGE syndrome. We observed a
      CHARGE syndrome patient with chromodomain helicase DNA-binding protein 7 mutation
      showing DiGeorge sequence including the defect of T cells accompanied with the
      aplasia of the thymus, severe hypoparathyroidism, and conotruncal cardiac
      anomaly. He received unrelated cord blood transplantation without conditioning at
      4 months of age. Recovery of T cell number and of proliferative response against
      mitogens was achieved by peripheral expansion of mature T cells in cord blood
      without thymic output. Although he is still suffering from severe
      hypoparathyroidism, he is alive without serious infections for 10 months.

PMID- 20052491
TI  - Clinical practice. Static, axial, and rotational deformities of the lower
      extremities in children.
AB  - Static, axial, and rotational deformities of the lower extremities are very
      frequent in children and often a reason for clinic visits. It is important to
      make a difference between physiological, usually spontaneously healing
      conditions, and real pathology. Flatfeet and less frequently cavus feet are the
      main foot problems. Special attention should be paid to the cavovarus foot that
      often has an underlying neurological disorder. Localized foot pain has usually a
      very specific cause and needs further investigation. Genua valga and genua vara
      are typical for a given age group and correct usually spontaneously. Toeing in
      and toeing out are mainly cosmetic problems and can be caused by tibial or
      femoral rotation, very rarely by a foot deformity. Leg length discrepancy is also
      frequent and in most patients limited to less than 2 cm, causing no further
      problems. Follow-up is, however, needed because of possible increasing
      discrepancy during growth.

PMID- 20052492
TI  - Priority effects and habitat complexity affect the strength of competition.
AB  - Both habitat complexity and priority effects can influence the strength of
      competitive interactions; however, the independent and synergistic effects of
      these processes are not well understood. In Moorea, French Polynesia, we
      conducted a factorial field experiment to quantify the independent and combined
      effects of priority effects and habitat complexity on the strength of
      intraspecific competitive interactions among recently settled individuals of a
      coral reef fish (Thalassoma quinquevittatum: Labridae). Simultaneous arrival of
      focal individuals with competitors resulted in a 2.89-fold increase in survival
      relative to reefs where focal individuals arrived 5 days later than competitors
      (i.e., a priority effect). Increasing habitat complexity resulted in a 1.55-fold
      increase in survivorship when focal individuals arrived simultaneously with or
      before competitors. However, increasing habitat complexity did not affect the
      survivorship of focal individuals arriving 5 days later than competitors.
      Behavior observations showed that survivorship was negatively correlated with
      aggression. Aggression by prior residents towards focal individuals was
      significantly greater when focal individuals arrived 5 days later than
      competitors than when they arrived simultaneously. Increasing habitat complexity
      did not reduce aggression. Our results suggest that, when competitors arrive
      simultaneously, competitive interactions are weak and subordinates are not
      displaced from complex habitat; increasing habitat complexity increases survival
      by disrupting predation. Conversely, when competitors arrive at different times,
      aggression intensifies and increasing habitat complexity does not disrupt
      predation because competitive subordinates are excluded from habitat resources.
      This study demonstrates that the strength of competition can be context-dependent
      and may vary with the timing of competitive interactions and habitat complexity.

PMID- 20052493
TI  - Body condition is associated with adrenocortical response in the barn swallow
      (Hirundo rustica L.) during early stages of autumn migration.
AB  - Migration is an energy-demanding life-history period and also a significant
      population-limiting factor of long-distance migratory birds. It is important to
      understand how corticosterone, the main energy regulating hormone in birds, is
      associated with behavioural and physiological changes during migration. According
      to the migration modulation hypothesis (MMH), individual birds may express
      elevated levels of baseline corticosterone to facilitate fuelling, but down
      regulate the adrenocortical response in order to protect skeletal muscles from
      the catabolic effects of the hormone. We measured the baseline and stress-induced
      levels of corticosterone in barn swallows (Hirundo rustica L.) during early
      stages of autumn migration. Here, we show that, while barn swallows clearly
      responded to the capture and handling stress by increasing the corticosterone
      level, the strength of this acute response was related to their energetic
      condition: birds with high body mass responded more rapidly and had lower peak
      values of corticosterone than lighter birds. Further, the baseline levels of
      corticosterone correlated negatively with the magnitude of the adrenocortical
      response. Barn swallows did not show elevated baseline levels of corticosterone
      in the course of autumn, which suggests that, instead of fuelling, the birds were
      actively migrating. Our results indicate that MMH also applies to aerial feeders,
      whose foraging habits differ from model birds of previous studies.

PMID- 20052494
TI  - Linking snake habitat use to nest predation risk in grassland birds: the dangers
      of shrub cover.
AB  - Extremes in rangeland management, varying from too-frequent fire and intensive
      grazing to the suppression of both, threaten rangeland ecosystems worldwide.
      Intensive fire and grazing denude and homogenize vegetation whereas their
      suppression increases woody cover. Although habitat loss is implicated in
      grassland bird declines, degradation through intensive management or neglect also
      decreases breeding habitat and may reduce nesting success through increased rates
      of nest predation. Snakes are important nest predators, but little is known about
      how habitat use in snakes relates to predation risk for grassland birds nesting
      within tallgrass prairie subjected to different grazing and fire frequencies. We
      evaluated nest survival in the context of habitat used by nesting songbirds and
      two bird-eating snakes, the eastern yellowbelly racer Coluber constrictor
      flaviventris and Great Plains ratsnake Pantherophis emoryi. Daily nest survival
      rates decreased with increasing shrub cover and decreasing vegetation height,
      which characterize grasslands that have been neglected or intensively managed,
      respectively. Discriminant function analysis revealed that snake habitats were
      characterized by higher shrub cover, whereas successful nests were more likely to
      occur in areas with tall grass and forbs but reduced shrub cover. Because snakes
      often use shrub habitat, birds nesting in areas with increased shrub cover may be
      at higher risk of nest predation by snakes in addition to other predators known
      to use shrub habitat (e.g., mid-sized carnivores and avian predators). Depredated
      nests also occurred outside the discriminant space of the snakes, indicating that
      other predators (e.g., ground squirrels Spermophilus spp. and bullsnakes
      Pituophis catenifer) may be important in areas with denuded cover. Targeted
      removal of shrubs may increase nest success by minimizing the activity of nest
      predators attracted to shrub cover.

PMID- 20052496
TI  - Airway management in an infant with double aortic arch.
AB  - A 2-month old male was admitted due to repeated cyanotic attacks. He had suffered
      from stridor and retractive breathing since birth. Double aortic arch was
      diagnosed and the vascular ring formed by the double aortic arch was compressing
      the trachea. Multirow detector computed tomography showed that he had a right
      dominant double aortic arch with left ductus arteriosus and an aberrant left
      subclavian artery, and that the narrowest part of the trachea, where the diameter
      was 2.0 mm, was located 9.0 mm above the carina. Airway management in patients
      with extreme narrowing of the trachea is challenging for anesthesiologists. He
      was scheduled for ligation and division of the left aortic arch and ductus
      arteriosus. In the operating theater, anesthesia was slowly induced with
      sevoflurane (0-4%) in oxygen. After mask ventilation was confirmed to be
      adequate, a 4.0 mm internal diameter endotracheal tube (ETT) was inserted and
      advanced smoothly beyond the tracheal stenosis. The tip of the ETT was placed
      just above the carina using a fiber optic bronchoscope (fiberscope) that was
      passed through the ETT. Since mechanical ventilation was adequate, vecuronium was
      administered. Surgery was conducted in the right lateral position and using a
      left thoracotomy approach. Anesthesia was maintained with sevoflurane (2-3%).
      After positioning, right one-lung ventilation was performed unexpectedly.
      However, anesthetic management was achieved without difficult ventilation during
      surgery. The tip of the ETT was pulled past the stenotic part before transfer to
      the intensive care unit (ICU). A patent trachea during spontaneous breathing
      under CPAP (5 and 2 cmH(2)O) was confirmed with a bronchofiberscope in the ICU.
      After weaning from mechanical ventilation, he had the persistence of mild stridor
      despite improvement of respiratory symptoms.

PMID- 20052497
TI  - The effect of landiolol on cerebral blood flow in patients undergoing off-pump
      coronary artery bypass surgery.
AB  - PURPOSE: To examine the effect of landiolol on cerebral blood flow in patients
      with normal or deteriorated cardiac function. METHODS: Thirty adult patients who
      were diagnosed with angina pectoris and who underwent elective off-pump coronary
      artery bypass surgery were studied. Patients were divided into two groups, one
      with a preoperative left ventricular ejection fraction (EF) of 50% or higher
      (normal EF group; n = 15) and the other with an EF of less than 50% (low EF
      group; n = 15). The mean cerebral blood flow velocity (Vmca) and pulsatility
      index (PI) in the middle cerebral artery were recorded using transcranial Doppler
      ultrasonography (TCD). Individual hemodynamic data were obtained using a
      pulmonary arterial catheter. RESULTS: In both groups, landiolol produced a
      significant decrease in heart rate (HR), which then returned to baseline 15 min
      after administration was completed. A significant decrease in mean arterial
      pressure occurred in the low EF group, but the decrease was within 30% of the
      baseline. In the normal EF group, there was no decrease in cardiac index (CI),
      whereas in the low EF group, CI significantly decreased along with the decrease
      in HR. There were no significant differences in Vmca and PI between the two
      groups. CONCLUSION: Continuous administration of landiolol at a dose of 0.04
      mg/kg/min after 1 min rapid i.v. administration at a dose of 0.125 mg/kg/min
      decreases HR without causing aggravation of CBF during treatment of
      intraoperative tachycardia in patients with normal and deteriorated cardiac
      function.

PMID- 20052498
TI  - Unsuspected tracheal web inhibits endotracheal intubation: report of a case.
AB  - A 66-year-old woman was scheduled for resection of a recurrent brain astrocytoma.
      During anesthesia induction, endotracheal intubation became impossible. Urgent
      bronchoscopy under laryngeal mask ventilation visualized a subglottic web 1 cm
      below the vocal cords. After bronchoscopic ablation with argon plasma
      coagulation, the airway intubation was successful.

PMID- 20052500
TI  - Use of Schroeder directional stylet to enhance navigability during nasotracheal
      intubation.

PMID- 20052499
TI  - Suspected recurrent anaphylaxis in different forms during general anesthesia.
AB  - We report on a patient who presented with recurrent severe shock during general
      anesthesia. The patient was a man scheduled for lung surgery whose first attack
      was a coronary spasm, which was followed by a second shock with severe
      bronchospasm and hypotension 4 weeks later. An elevated serum tryptase
      concentration was observed, and subsequent skin testing revealed negative
      reactions to some drugs administered in this case. This case serves to alert
      anesthetists to the possibility of some different forms of allergy and highlights
      the importance of rigorous investigation of all the reagents and phenomena.

PMID- 20052501
TI  - Anesthesia management for emergency laparotomy in a pediatric patient with
      suspected hereditary angioedema.
AB  - Hereditary angioedema (HAE) is caused by complement factor 1 inhibitor (C1-INH)
      deficiency, and its mode of inheritance is autosomal dominant. We present a case
      of an 8-year-old patient who required emergency laparotomy after a traffic
      accident. General anesthesia with tracheal intubation was necessary. The
      patient's mother and maternal grandmother had been diagnosed with HAE. HAE is
      associated with high mortality when airway edema is caused by tracheal
      intubation. It was impossible to rule out HAE preoperatively in the patient.
      Therefore, we presumed that he had HAE and treated him with pasteurized C1-INH
      concentrate. The patient underwent laparotomy uneventfully. Several days after
      the operation, the laboratory data revealed that the perioperative plasma
      complement 1 q subunit (C1q) protein level and C1-INH function were not lowered.
      The diagnosis of HAE was not confirmed, but it was not possible to rule out the
      diagnosis either. The prophylactic use of a C1-INH in this case may be justified,
      because the procedure was an emergency and because of the high mortality
      associated with tracheal intubation in patients with HAE.

PMID- 20052502
TI  - Dexamethasone before total laparoscopic hysterectomy: a randomized controlled
      dose-response study.
AB  - PURPOSE: A prospective, randomized, double blind, placebo-controlled study was
      undertaken to evaluate the efficacy of a single preoperative dose of
      dexamethasone, in different dosages, in providing postoperative analgesia in
      patients undergoing total laparoscopic hysterectomy (TLH). METHOD: The study
      included 55 patients randomly divided into three groups. Patients in Groups P,
      D4, and D8 received saline, 4, and 8 mg dexamethasone, respectively,
      intravenously, 2 h before induction. RESULTS: The time to first analgesic
      requirement was significantly delayed in patients in the D8 group compared with
      the D4 group (P = 0.01) and placebo (P = 0.01). Total postoperative fentanyl
      consumption was significantly less in patients in the D8 group compared with the
      D4 group (P = 0.01) and placebo (P = 0.01). Use of 8 mg dexamethasone resulted in
      a 99.3 mcg decrease in total 24-h fentanyl consumption. Postoperative nausea and
      vomiting (PONV) was significantly less in the D8 group with a complete response
      rate (no emetic episodes and no rescue medication for 24 h) of 36.8% compared
      with the placebo group in which all the patients had PONV. No adverse effects
      were observed in any group. CONCLUSION: Dexamethasone at a dose of 8 mg given
      intravenously 2 h before induction, delays patient request for analgesia and
      reduces total fentanyl consumption and PONV in patients undergoing TLH.

PMID- 20052503
TI  - Gastric bleeding detected by transesophageal echocardiography during
      cardiopulmonary bypass.
AB  - Gastric bleeding during cardiopulmonary bypass (CPB) is a rare but life
      threatening complication for patients undergoing cardiac surgery. We present a
      case of a patient undergoing coronary bypass grafting in whom we detected gastric
      bleeding by transesophageal echocardiography (TEE) during CPB. After separation
      from CPB, bleeding was stopped by endoscopic clipping of the mucosa. If a fluid
      deficit is noted and TEE reveals a hypoechoic space within the stomach, gastric
      bleeding might be suggested.

PMID- 20052504
TI  - Functional outcome of computer-assisted spinal pedicle screw placement: a
      systematic review and meta-analysis of 23 studies including 5,992 pedicle screws.
AB  - A number of studies have shown increased accuracy of pedicle screw placement in
      spine with the help of computer-assisted navigation. The literature is lacking in
      regard to functional benefit derived from this technique. The aim of this
      systematic review was to look at the functional outcomes following computer
      assisted pedicle screw placement in spine. A 'Dialog Datastar' search was used
      using optimized search strategy covering the period from 1950 to July 2009; 23
      papers were finally included which met our inclusion criteria. We report on a
      total of 1,288 patients with 5,992 pedicle screws. The comparison of neurological
      complications in two groups demonstrated an odds ratio of 0.25 (95% CI 0.06,
      1.14) in favour of using navigation for pedicle screw insertion (p = 0.07).
      Comparative trials demonstrated a significant advantage in terms of accuracy of
      navigation over conventional pedicle screw insertion with a relative risk of 1.12
      (95% CI 1.09, 1.15) (p < 0.00001). Navigation does not show statistically
      significant benefit in reducing neurological complications and there was
      insufficient data in the literature to infer a conclusion in terms of fusion
      rate, pain relief and health outcome scores.

PMID- 20052505
TI  - Expanding role of 18F-fluoro-D-deoxyglucose PET and PET/CT in spinal infections.
AB  - (18)F-fluoro-D -deoxyglucose positron emission tomography ([(18)F]-FDG PET) is
      successfully employed as a molecular imaging technique in oncology, and has
      become a promising imaging modality in the field of infection. The non-invasive
      diagnosis of spinal infections (SI) has been a challenge for physicians for many
      years. Morphological imaging modalities such as conventional radiography,
      computed tomography (CT), and magnetic resonance imaging (MRI) are techniques
      frequently used in patients with SI. However, these methods are sometimes non
      specific, and difficulties in differentiating infectious from degenerative end
      plate abnormalities or postoperative changes can occur. Moreover, in contrast to
      CT and MRI, FDG uptake in PET is not hampered by metallic implant-associated
      artifacts. Conventional radionuclide imaging tests, such as bone scintigraphy,
      labeled leukocyte, and gallium scanning, suffer from relatively poor spatial
      resolution and lack sensitivity, specificity, or both. Initial data show that
      [(18)F]-FDG PET is an emerging imaging technique for diagnosing SI. [(18)F]-FDG
      PET appears to be especially helpful in those cases in which MRI cannot be
      performed or is non-diagnostic, and as an adjunct in patients in whom the
      diagnosis is inconclusive. The article reviews the currently available literature
      on [(18)F]-FDG PET and PET/CT in the diagnosis of SI.

PMID- 20052506
TI  - Activation of 5-HT3 receptors leads to altered responses 6 months after MDMA
      treatment.
AB  - The recreational drug "Ecstasy" [3,4-methylenedioxymethamphetamine (MDMA)] has a
      well-characterised neurotoxic effect on the 5-hydroxytryptamine (5-HT) neurons in
      animals. Despite intensive studies, the long-term functional consequencies of the
      5-HT neurodegeneration remains elusive. The aim of this study was to investigate
      whether any alteration of 5-hydroxytryptamine-3 (5-HT(3)) receptor functions on
      the sleep-wake cycle, motor activity, and quantitative EEG could be detected 6
      months after a single dose of 15 mg/kg of MDMA. The selective 5-HT(3) receptor
      agonist m-chlorophenylbiguanide (mCPBG; 1 mg/kg, i.p.) or vehicle was
      administered to freely moving rats pre-treated with MDMA (15 mg/kg, i.p.) or
      vehicle 6 months earlier. Polysomnographic and motor activity recordings were
      performed. Active wake (AW), passive wake (PW), light slow wave sleep (SWS-1),
      deep slow wave sleep (SWS-2), and paradoxical sleep were classified. In addition,
      EEG power spectra were calculated for the second hour after mCPBG treatment for
      each stage. AW increased and SWS-1 decreased in the second hour after mCPBG
      treatment in control animals. mCPBG caused significant changes in the EEG power
      in states with cortical activation (AW, PW, paradoxical sleep). In addition,
      mCPBG had a biphasic effect on hippocampal theta power in AW with a decrease in 7
      Hz and a stage-selective increase in the upper range (8-9 Hz). Effects of mCPBG
      on the time spent in AW and SWS-1 were eliminated or reduced in MDMA-treated
      animals. In addition, mCPBG did not increase the upper theta power of AW in rats
      pre-treated with MDMA. These data suggest long-term changes in 5-HT(3) receptor
      function after MDMA.

PMID- 20052507
TI  - Reactive oxygen species formation and cell death in catalase-deficient tobacco
      leaf disks exposed to cadmium.
AB  - The physiological responses of tobacco (Nicotiana tabacum L.) to oxidative stress
      induced by cadmium were examined with respect to reactive oxygen species (ROS)
      formation, antioxidant enzymes activities, and cell death appearance in wild-type
      SR1 and catalase-deficient CAT1AS plants. Leaf disks treated with 100 or 500
      microM CdCl(2) increased Evans blue staining and leakage of electrolytes in SR1
      or CAT1AS plants, more pronouncedly in the transgenic cultivar, but without
      evidence of lipid peroxidation in any of the cultivars compared to controls.
      Cadmium significantly reduced the NADPH oxidase-dependent O (2)(-) formation in a
      dose dependent manner in SR1 very strongly at 500 microM (to 5% of the activity
      in the nontreated SR1 leaf disks). In CAT1AS, the NADPH oxidase activity was
      constitutively reduced at 50% with respect to that of SR1, but the magnitude of
      the decay was less prominent in this cultivar, reaching an average of 64% of the
      C at 21 h, for both Cd concentrations. Hydrogen peroxide formation was only
      slightly increased in SR1 or CAT1AS leaf disks at 21 h of exposure compared to
      the respective controls. Cd increased superoxide dismutase activity more than six
      times at 21 h in CAT1AS, but not in SR1 and reduced catalase activity by 59% at
      21 h of treatment only in SR1 plants. Despite that catalase expression was
      constitutively lower in CATAS1 compared to SR1 nontreated leaf disks, 500 microM
      CdCl(2) almost doubled it only in CAT1AS at 21 h. The mechanisms underlying Cd
      induced cell death were possibly not related exclusively to ROS formation or
      detoxification in tobacco SR1 or CAT1AS plants.

PMID- 20052508
TI  - Impact of bifunctional chelators on biological properties of 111In-labeled cyclic
      peptide RGD dimers.
AB  - The present study describes the synthesis and biological evaluation of
      (111)In(DOTA-3P-RGD(2)) (DOTA = 1,4,7,10-tetraazacyclo-dodecane-1,4,7,10
      tetraacetic acid; 3P-RGD(2) = PEG(4)-E[PEG(4)-c(RGDfK)](2); PEG(4) = 15-amino
      4,7,10,13-tetraoxapentadecanoic acid), (111)In(DTPA-3P-RGD(2)) (DTPA =
      diethylenetriaminepentaacetic acid) and (111)In(DTPA-Bn-3P-RGD(2)) (DTPA-Bn = 2
      (p-thioureidobenzyl)-diethylenetriaminepentaacetic acid) as potential
      radiotracers for imaging tumor integrin alpha(v)beta(3) expression in athymic
      nude mice bearing U87MG glioma xenografts. The aim of the study is to assess the
      impact of the bifunctional chelator (BFC) (DOTA vs. DTPA or DTPA-Bn) on the
      biodistribution characteristics of the (111)In-labeled 3P-RGD(2). IC(50) values
      of DOTA-3P-RGD(2), DTPA-3P-RGD(2) and DTPA-Bn-3P-RGD(2) were determined to be 1.3
      +/- 0.2, 1.4 +/- 0.3, 1.3 +/- 0.3 nM, respectively, against (125)I-c(RGDyK) bound
      to U87MG human glioma cells. Radiotracers were prepared by reacting (111)InCl(3)
      with the RGD peptide conjugates in NH(4)OAc buffer (100 mM, pH 5.5). For DOTA-3P
      RGD(2), successful radiolabeling could be completed by heating the reaction
      mixture at 100 degrees C for 15-20 min. For DTPA-3P-RGD(2) and DTPA-Bn-3P-RGD(2),
      the radiolabeling was almost instantaneous at room temperature. The specific
      activity was ~50 mCi/mg (or ~100 mCi/MUmol) for (111)In(DOTA-3P-RGD(2)) and ~200
      mCi/mg (or ~400 mCi/MUmol) for (111)In(DTPA-3P-RGD(2)). The results from
      biodistribution studies showed that all the three radiotracers have high tumor
      uptake and excellent tumor-to-background (T/B) ratios up to 4-h postinjection.
      After that time point, both (111)In(DTPA-3P-RGD(2)) and (111)In(DTPA-Bn-3P
      RGD(2)) showed a much faster tumor washout and poorer T/B ratios than
      (111)In(DOTA-3P-RGD(2)). The tumor uptake of (111)In(DOTA-3P-RGD(2)) is integrin
      alpha(v)beta(3)- and RGD-specific. (111)In(DOTA-3P-RGD(2)) is metabolically
      stable while only ~25% of (111)In(DTPA-Bn-3P-RGD(2)) remains intact in the feces
      during 2-h period. On the basis of results from this study, it was concluded that
      (111)In(DTPA-3P-RGD(2)) can be an effective integrin alpha(v)beta(3)-targeted
      radiotracer if the high-specific activity is required. However, DOTA remains to
      be the BFC of choice for the development of therapeutic lanthanide radiotracers.

PMID- 20052509
TI  - Chronic pain after open inguinal hernia repair: a longitudinal self-assessment
      study.
AB  - INTRODUCTION: The aim of the present study was to assess the variation of self
      reported pain over a period of 2 years in three groups of patients with no,
      moderate and severe pain at 3 months after primary open inguinal hernia repair.
      METHODS: In two cohorts of patients from 2004 (n = 272) and 2005 (n = 292) who
      had given a self-report of postoperative pain at 3 months, 79 randomly selected
      patients without pain (box visual analogue scale [VAS] level 10) and all patients
      with moderate (Box VAS level 7-9) and severe pain (Box VAS level 1-6), 91 and 9,
      respectively, were included in the case series. The self-assessments were
      repeated for all patients 1-1.5 and 2-2.5 years after surgery (November 2006).
      RESULTS: It was observed that moderate pain reappeared among the pain-free
      patients in 28 and 23% after 1-1.5 and 2-2.5 years, respectively. Of those
      patients with moderate pain at 3 months, 39 and 49% reported 'no pain' at 1-1.5
      and 2-2.5 years, respectively, after surgery. A worsening from moderate pain to
      severe pain was reported by 22% of patients after 1-1.5 years and by 15% of
      patients after 2-2.5 years. Hernia recurrence (n = 3) was observed only in
      patients with increased pain. All nine patients with severe pain at 3 months
      reported less pain, but only one was pain-free at 2-2.5 years after surgery.
      CONCLUSION: The study shows that a significant proportion of the patients
      developed pain later than 3 months after the operation. It further points to a
      difference in pain evolvement in patients with moderate pain and those with
      severe postoperative pain at 3 months. Pain can increase in intensity from
      moderate to severe, both with and without the presence of a clinical recurrence.

PMID- 20052510
TI  - Pubic inguinal pain syndrome: the so-called sports hernia.

PMID- 20052511
TI  - Anti-cyclic citrulline peptide antibody in non-tuberculous mycobacteria sera: a
      negative association.

PMID- 20052512
TI  - Perception of biological motion in common marmosets (Callithrix jacchus): by
      females only.
AB  - The ability to perceive biological motion (BM) has been demonstrated in a number
      of species including humans but the few studies of non-human primates have been
      relatively inconclusive. We investigated whether common marmosets (Callithrix
      jacchus) are able to perceive biological motion, using a novel method to test non
      human primates. Marmosets (7 male and 7 female) were trained to remove a cover
      from a container and look inside it, revealing a computer screen. Then they were
      presented with images on this computer screen consisting of a novel BM pattern (a
      walking hen) and 4 manipulations of that pattern (a static frame of this pattern
      and inverted, scrambled, and rotating versions of the pattern). The behavioural
      responses of the marmosets were recorded and used to assess discrimination
      between stimuli. BM was attended to by females but not males, as shown by active
      inspection behaviour, mainly movement of the head towards the stimulus. Females
      paid significantly less attention to all of the other stimuli. This indicates the
      females' ability to attend to biological motion. Females showed slightly more
      attention to the inverted BM than to the static, scrambled, and rotating
      patterns. The males were less attentive to all of the stimuli than were the
      females and, unlike the females, responded to all stimuli in a similar manner.
      This sex difference could be due to an inability of males to recognise BM
      altogether or to a lesser amount of curiosity. Considered together with the
      findings of previous studies on chicks and humans, the results of the present
      study support the notion of a common mechanism across species for the detection
      of BM.

PMID- 20052513
TI  - Clinical aspects of invasive infection with Streptococcus dysgalactiae subsp.
      equisimilis in elderly patients.
AB  - The number of patients with severe invasive infections (mainly exhibiting
      bacteremia) with Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been
      increasing worldwide. We herein report the clinical aspects of invasive
      infections (cellulitis, pneumonia, and urosepsis) occurring with SDSE in 13
      elderly patients (mean age 84 years, range 69-99 years) diagnosed at a hospital
      for elderly individuals during the period January 2005-June 2009. Ten subjects
      had underlying diseases, including neurologic disorders, diabetes mellitus, and
      others. Eleven patients presented to the hospital emergency department, and the
      most common symptom was high fever or respiratory distress. Primary care and
      emergency department doctors treating elderly patients with high fever should
      keep in mind invasive SDSE infection as a differential diagnosis, especially when
      an elderly person has underlying illnesses. To detect SDSE in elderly subjects,
      blood cultures should be obtained before the administration of antimicrobials
      because, as we found, the patients' symptoms were limited.

PMID- 20052514
TI  - Tuberculosis diagnosed by PCR analysis of synovial fluid.
AB  - Tuberculosis is a leading cause of mortality due to an infectious agent
      worldwide. It often affects multiple organs by hematogenous spread of
      Mycobacterium tuberculosis, but knee-joint involvement is extremely rare,
      comprising approximately 0.1% of all forms of tuberculosis. We present a case of
      tuberculous pleuritis with knee-joint involvement. Cytological and biochemical
      analysis of the pleural fluid and a biopsy specimen of the cervical lymph node
      indicated tuberculosis, but a definitive diagnosis was not given. A confirmed
      diagnosis was finally obtained through PCR analysis of the synovial fluid.
      Tuberculosis should be included in the differential diagnosis in patients with
      persistent pain and swelling of the knee. PCR analysis of the synovial fluid is a
      quick and useful method for the diagnosis.

PMID- 20052515
TI  - The effect of health care expenditure on sickness absence.
AB  - Increased health care expenditure could be used to improve quality of care or
      reduce waiting time and could therefore be expected to affect the health and
      sickness absence of a population. Still, based on data from a panel of Swedish
      municipalities, public health care expenditure was found to have no, or only a
      negligible effect on absence due to sickness or disability. The same result was
      obtained when separate estimates were done for men and women and for absence due
      to sickness and disability.

PMID- 20052516
TI  - Why does biparental plastid inheritance revive in angiosperms?
AB  - It is widely believed that plastid and mitochondrial genomes are inherited
      through the maternal parent. In plants, however, paternal transmission of these
      genomes is frequently observed, especially for the plastid genome. A male gametic
      trait, called potential biparental plastid inheritance (PBPI), occurs in up to
      20% of angiosperm genera, implying a strong tendency for plastid transmission
      from the male lineage. Why do plants receive organelles from the male parents?
      Are there clues in plastids that will help to elucidate the evolution of plants?
      Reconstruction of the ancestral state of plastid inheritance patterns in a
      phylogenetic context provides insights into these questions. In particular, a
      recent report demonstrated the unilateral occurrence of PBPI in angiosperms. This
      result implies that nuclear cytoplasmic conflicts, a basic driving force for
      altering the mode of organelle inheritance, might have arisen specifically in
      angiosperms. Based on existing evidence, it is likely that biparental inheritance
      may have occurred to rescue angiosperm species with defective plastids.

PMID- 20052517
TI  - Grid-free interactive and automated data processing for MR chemical shift imaging
      data.
AB  - PURPOSE: Today's available chemical shift imaging (CSI) analysis tools are based
      on Fourier transform of the entire data set prior to interactive display. This
      strategy is associated with limitations particularly when arbitrary voxel
      positions within a 3D spatial volume are needed by the user. In this work, we
      propose and demonstrate a processing-resource-efficient alternative strategy for
      both interactive and automated CSI data processing up to three spatial
      dimensions. METHODS: This approach uses real-time voxel-shift by first-order
      phase manipulation as a basis and therefore allows grid-free voxel positioning
      within the 3D volume. The corresponding spectrum is extracted from the 4D data
      (3D spatial/1D spectral) at each time a voxel position is selected. The spatial
      response function and hence the exact voxel size and shape are calculated in
      parallel including the same processing parameters. Using this mechanism
      sequentially along with AMARES time-domain modeling, we also implemented
      automated quantitative and B (0)-insensitive metabolite mapping. RESULTS:
      Metabolite maps of N-acetyl aspartate, choline and creatine were generated using
      (1)H-CSI data from the brain of healthy volunteers and patients with tumor and
      epilepsy. (31)P-3D-CSI of the heart of a healthy volunteer is also shown.
      CONCLUSION: The calculated metabolite maps demonstrate good stability and
      accuracy of the algorithm in all situations tested. The suggested algorithm
      constitutes therefore an attractive alternative to existing CSI processing
      strategies.

PMID- 20052518
TI  - Cytogenetic analysis of paediatric astrocytoma using comparative genomic
      hybridisation and fluorescence in-situ hybridisation.
AB  - Little is known about the cytogenetic and molecular genetic events that lead to
      the formation of paediatric astrocytoma. We have analysed 57 paediatric
      astrocytoma (WHO grades I-IV) using comparative genomic hybridisation in order to
      identify common regions of abnormality. Large regions of copy number alterations
      were infrequent with 71% of tumours demonstrating no genomic imbalance.
      Furthermore, the most frequent aberrations (including gain of 6q, 2q, and 7q, and
      loss of 16 and 12q) occurred in only a subset of cases. High-copy number
      amplification was seen in five tumours at 12 different regions. The presence of
      copy number alterations was significantly associated with increasing grade of
      malignancy, and gain of 12q and the presence of high-copy number amplification
      were associated with a poor outcome in patients with malignant astrocytoma (P =
      0.0039 and 0.0085, respectively). FISH analysis confirmed loss of 1p36 identified
      by CGH. There was no evidence of amplification of EGFR, CDK4, MET, CDK6, c-myc,
      or MDM2.

PMID- 20052519
TI  - Kinetic studies of a composite carbon nanotube-hydrogel for tissue engineering by
      rheological methods.
AB  - Here we used rheological methods to study the gelation kinetics of silanized
      hydroxypropylmethylcellulose (HPMC-Si) hydrogel for tissue engineering. Firstly,
      the gelation time was determined from the independence of tan delta on frequency,
      and the Arrhenius law was applied to obtain the apparent activation energy of
      gelation, which was found to be about 109.0 kJ/mol. Secondly, the gelation
      process was monitored by measuring the sample storage modulus. The results showed
      that the gelation process could be well classified as a second-order reaction. In
      addition, a composite HPMC-Si/MWNTs hydrogel system for potential cartilage
      tissue engineering was investigated. The comparison of pure HPMC-Si hydrogel and
      composite HPMC-Si/MWNTs systems indicated that the addition of MWNTs could
      increase the mechanical strength of hydrogel without changing the gelation
      mechanism of the system.

PMID- 20052520
TI  - Sensing of protein adsorption with a porous bulk composite comprising silver
      nanoparticles deposited on hydroxyapatite.
AB  - Porous bulk composites were produced by depositing silver nanoparticles of
      diameter 11.0 +/- 3.2 nm on hydroxyapatite of micrometer sizes. Adsorption of
      bovine serum albumin (BSA) and lysozyme (LSZ) on the composite material was
      observed in 2 and 10 mol m(-3) phosphate buffer solutions. More BSA than LSZ was
      adsorbed in 2 mol m(-3) phosphate buffer and this was attributed to a larger a
      face surface area present in the plate- and rod-shaped hydroxyapatite compared
      with the c-face surface area. Peak shifts in localized surface plasmon resonance
      (LSPR) spectra were clearly related to adsorbed amounts of BSA and LSZ after
      exposure of the porous bulk composites to protein solutions. The sensing
      capability of the porous bulk composite results from changes in the dielectric
      constant of the surface fluid surrounding the silver nanoparticles.
      Adsorption/desorption cycles of BSA were applied to the porous bulk composite,
      confirming the reversibility of the sensing capability.

PMID- 20052521
TI  - Synthesis of nano-sized biphasic calcium phosphate ceramics with spherical shape
      by flame spray pyrolysis.
AB  - Nanometer size biphasic calcium phosphate (BCP) powders with various Ca/P molar
      ratios satisfied with appropriate phase ratios of HA/beta-TCP were prepared by
      high temperature flame spray pyrolysis process. The BCP powders had spherical
      shapes and narrow size distributions irrespective of the ratios of Ca/P. The mean
      size of the BCP powders measured from the TEM image was 38 nm. The composition
      ratio of Ca/P was controlled from 1.500 to 1.723 in the spray solution, and
      required phase ratios of HA/TCP are controlled systematically. The calcium
      dissolution of the pellets obtained from the BCP powders directly prepared by
      flame spray pyrolysis in buffer solution increased with the decrease of Ca/P
      ratios except with the Ca/P ratio of 1.713. The pellet surface with Ca/P ratio of
      1.500, which consisted of beta-TCP, was eroded dramatically for 7 days. On the
      other hand, the pellet surface with Ca/P ratio of 1.667 was stable and did not
      disintegrate after immersion in Tris-HCl buffer solution based on the SEM
      observation.

PMID- 20052522
TI  - Cyclooxygenase-2 expression in astrocytes and microglia in human
      oligodendroglioma and astrocytoma.
AB  - Cyclooxygenases (cox) are potent mediators of inflammation and two cox
      isoenzymes, cox-1, cox-2, are described to date. Cox-2 is cytokine-inducible in
      inflammatory cells and enhanced cox-2 expression has been attributed a key role
      in the development of edema and immunomodulation in pathologically altered brain
      tissues. In normal cerebral cortex cox-2 is present only in neurons, but not in
      the glial or vascular endothelial cells. The function of microglia in glioma
      biology is unclear. Microglia have both neurotrophic and neurotoxic functions and
      have been shown to release a variety of cytokines. Our preliminary results showed
      that the expression pattern of cox-2 is predominantly neuronal although glial
      expression was observed with the correlation of high malignancy. In this study we
      aimed to assess the phenotypes (astrocyte, microglia) of the cox-2-expressing
      glial cells in various types of human gliomas and to compare their expression
      patterns. For this purpose we employed dual immunohistochemistry for cox-2 and
      GFAP (astrocyte) or LCA-MAC (microglia-macrophage) in archival formalin-fixed,
      paraffin embedded human tissue diagnosed as oligodendroglioma and/or astrocytoma.
      The results showed that cox-2 immunoreactivity is up-regulated in the neurons
      according to the tumor grade. Most of the cox-2 immunoreactive glia were GFAP
      positive in anaplastic oligodendrogliomas and at lesser extend in glioblastomas.
      Cox-2 and LCA co-localization was detected in more glial cells in glioblastomas.
      It may be speculated that the induction of cox-2 in microglia may contribute to
      the deleterious effects of prostanoids in cerebral edema formation during the
      progression of oligodendrogliomas. The detection of cox-2 in astrocytes
      surrounding the necrotic areas might be important to develop new strategies, such
      as the usage of cox-2 inhibitors combine with chemotherapy and radiotherapy in
      the treatment of glioma patients.

PMID- 20052523
TI  - Recurrence of medically certified sickness absence according to diagnosis: a
      sickness absence register study.
AB  - INTRODUCTION: Sickness absence is a major public health problem. Research on
      sickness absence focuses on interventions aimed at expediting return to work.
      However, we need to know more about sustaining employees at work after return to
      work. Therefore, this study investigated the recurrence of sickness absence
      according to diagnosis. METHODS: We analyzed the registered sickness absence data
      of 137,172 employees working for the Dutch Post and Telecom. Episodes of sickness
      absence were medically certified, according to the ICD-10 classification of
      diseases, by an occupational physician. The incidence density (ID) and recurrence
      density (RD) of medically certified absences were calculated per 1,000 person
      years in each ICD-10 category. RESULTS: Sickness absence due to musculoskeletal
      disorders had the highest recurrence (RD = 118.7 per 1,000 person-years),
      followed by recurrence of sickness absence due to mental disorders (RD = 80.4 per
      1,000 person-years). The median time to recurrent sickness absence due to
      musculoskeletal disorders was 409 days after the index episode. Recurrences of
      sickness absence due to musculoskeletal disorders accounted for 37% of the total
      number of recurrent sickness absence days. For recurrences of sickness absence
      due to mental disorders this was 328 days and 21%, respectively. Unskilled
      employees with a short duration (<5 years) of employment had a higher risk of
      recurrent sickness absence. CONCLUSIONS: Interventions to expedite return to work
      of employees sick-listed due to musculoskeletal or mental disorders should also
      aim at reducing recurrence of sickness absence in order to sustain employees at
      work.

PMID- 20052524
TI  - Multinomial logistic estimation of Markov-chain models for modeling sleep
      architecture in primary insomnia patients.
AB  - Hypnotic drug development calls for a better understanding of sleep physiology in
      order to improve and differentiate novel medicines for the treatment of sleep
      disorders. On this basis, a proper evaluation of polysomnographic data collected
      in clinical trials conducted to explore clinical efficacy of novel hypnotic
      compounds should include the assessment of sleep architecture and its drug
      induced changes. This work presents a non-linear mixed-effect Markov-chain model
      based on multinomial logistic functions which characterize the time course of
      transition probabilities between sleep stages in insomniac patients treated with
      placebo. Polysomnography measurements were obtained from patients during one
      night treatment. A population approach was used to describe the time course of
      sleep stages (awake stage, stage 1, stage 2, slow-wave sleep and REM sleep) using
      a Markov-chain model. The relationship between time and individual transition
      probabilities between sleep stages was modelled through piecewise linear
      multinomial logistic functions. The identification of the model produced a good
      adherence of mean post-hoc estimates to the observed transition frequencies.
      Parameters were generally well estimated in terms of CV, shrinkage and
      distribution of empirical Bayes estimates around the typical values. The
      posterior predictive check analysis showed good consistency between model
      predicted and observed sleep parameters. In conclusion, the Markov-chain model
      based on multinomial logistic functions provided an accurate description of the
      time course of sleep stages together with an assessment of the probabilities of
      transition between different stages.

PMID- 20052525
TI  - Multiplicatively interacting point processes and applications to neural modeling.
AB  - We introduce a nonlinear modification of the classical Hawkes process allowing
      inhibitory couplings between units without restrictions. The resulting system of
      interacting point processes provides a useful mathematical model for recurrent
      networks of spiking neurons described as Wiener cascades with exponential
      transfer function. The expected rates of all neurons in the network are
      approximated by a first-order differential system. We study the stability of the
      solutions of this equation, and use the new formalism to implement a winner-takes
      all network that operates robustly for a wide range of parameters. Finally, we
      discuss relations with the generalised linear model that is widely used for the
      analysis of spike trains.

PMID- 20052526
TI  - Molecular characterisation of African swine fever viruses from Nigeria (2003
      2006) recovers multiple virus variants and reaffirms CVR epidemiological utility.
AB  - Samples collected from wild and domestic suids in Nigeria, over a 3-year period
      (2003-2006), were evaluated for African swine fever (ASF) virus genome presence
      by targeting three discrete genome regions, namely the 478-bp C-terminal p72 gene
      region advocated for genotype assignment, a 780-bp region spanning the 5'-ends of
      the pB125R and pB646L (p72) genes and the hypervariable central variable region
      (CVR) encoded within the 9RL ORF (pB602L). ASF virus (ASFV) presence was
      confirmed in 23 of the 26 wild and domestic pigs evaluated. No evidence of ASF
      infection was found in two warthogs from Adamawa State; however, one bushpig from
      Plateau State was positive. Nucleotide sequences of the 478-bp and 780-bp
      amplicons were identical across all ASFV-positive samples sequenced. However,
      five discrete CVR variants were recovered, bringing the total number identified
      to date, from Nigeria, to six. The largest of the CVR variants, termed 'Tet-36'
      was identical to a virus causing outbreaks in neighbouring Benin in 1997,
      indicating a prolonged persistence of this virus type in Nigeria. Co-circulation
      of three tetramer types (Tet-36, Tet-27 and Tet-20) was found in Plateau State in
      July 2004, whilst in Benue State, two tetramer types (Tet-20 and Tet-21) were
      present in August 2005. Despite simultaneous field presence, individual co
      infection was not observed. This study has reaffirmed the epidemiological utility
      of the CVR genome region for distinguishing between geographically and temporally
      constrained genotype I viruses, and has revealed the presence of multiple ASFV
      variants in Nigeria.

PMID- 20052527
TI  - Life and death in aluminium-exposed cultures of rat lactotrophs studied by flow
      cytometry.
AB  - Prolonged exposure to aluminium may impact health. Aluminium's deleterious
      effects are mostly attributed to its selective accumulation in particular organs
      and cell types. Occupational exposure to aluminium is allied with a reduced level
      of serum prolactin, a stress peptide hormone mainly synthesised and secreted by
      the anterior pituitary lactotrophs. Our aim was to study the effect of aluminium
      on the viability of rat lactotrophs in primary suspension cultures where
      multicellular aggregates tend to form, comprising approximately two thirds of the
      total cell population as confirmed by confocal microscopy. Flow cytometric light
      scattering of calcein acetoxymethyl ester and ethidium homodimer-1 labelled cells
      was used to define subpopulations of live and dead cells in heterogeneous
      suspensions comprised of single cells and multicellular aggregates of distinct
      size. Concentration-dependent effects of AlCl(3) were observed on aggregate size
      and cell survival. After 24-h exposure to 3 mM AlCl(3), viability of single cells
      declined from 5% to 3%, while in multicellular aggregates, viability declined
      from 23% to 20%. The proportion of single cells increased from 30% to 42% within
      the same concentration range, while in large aggregates, the proportion remained
      approximately constant representing 35% of the cell suspension. In large
      aggregates, cell viability (75%) remained unaltered after exposure to AlCl(3)
      concentrations up to 300 microM, while in single cells, viability was halved at
      30 microM. In conclusion, our finding indicates that prolonged exposure to
      aluminium may lead to significant loss of pituitary cells.

PMID- 20052528
TI  - Multimodal integration of fMRI and EEG data for high spatial and temporal
      resolution analysis of brain networks.
AB  - Two major non-invasive brain mapping techniques, electroencephalography (EEG) and
      functional magnetic resonance imaging (fMRI), have complementary advantages with
      regard to their spatial and temporal resolution. We propose an approach based on
      the integration of EEG and fMRI, enabling the EEG temporal dynamics of
      information processing to be characterized within spatially well-defined fMRI
      large-scale networks. First, the fMRI data are decomposed into networks by means
      of spatial independent component analysis (sICA), and those associated with
      intrinsic activity and/or responding to task performance are selected using
      information from the related time-courses. Next, the EEG data over all sensors
      are averaged with respect to event timing, thus calculating event-related
      potentials (ERPs). The ERPs are subjected to temporal ICA (tICA), and the
      resulting components are localized with the weighted minimum norm (WMNLS)
      algorithm using the task-related fMRI networks as priors. Finally, the temporal
      contribution of each ERP component in the areas belonging to the fMRI large-scale
      networks is estimated. The proposed approach has been evaluated on visual target
      detection data. Our results confirm that two different components, commonly
      observed in EEG when presenting novel and salient stimuli, respectively, are
      related to the neuronal activation in large-scale networks, operating at
      different latencies and associated with different functional processes.

PMID- 20052529
TI  - Adherence to antiretroviral therapy in patients participating in a graduated cost
      recovery program at an HIV care center in South India.
AB  - In resource-constrained settings, the most frequently cited barrier to optimal
      antiretroviral therapy (ART) adherence among HIV-infected patients has been the
      cost of medications. In recent years many subsidized medication programs have
      been developed to improve ART affordability. A Graduated Cost Recovery program at
      the largest care center in South India has enrolled 839 eligible patients into
      four tiers based on an evaluation of their financial information and willingness
      to pay, of these patients 635 consented to participate in this study. Patients in
      Tier 1 receive first-line ART at no cost, whereas patients in Tiers 2, 3, and 4
      pay 50, 75, and 100%, respectively of the cost of first-line medications based on
      an assessment of their means. Adherence rates of 95% or greater on 3-day recall
      were achieved by 84.6% of Tier 1 (n = 156), 71.6% of Tier 2 (n = 141), 72.3% of
      Tier 3 (n = 242), and 79.2% of Tier 4 (n = 96). These findings suggest patients
      are highly motivated and that the provision of no-cost ART can promote higher
      rates of optimal adherence.

PMID- 20052530
TI  - Action brief: future directions in the implementation of evidence based treatment
      and practices in child and adolescent mental health.

PMID- 20052531
TI  - Genetic polymorphism of the beta-lactoglobulin gene in native sheep from India.
AB  - The genetic polymorphism of the beta-lactoglobulin (beta-LG) gene was determined
      in 638 animals belonging to 15 native Indian sheep breeds reared in different
      agroecological regions for various production traits. Variants of beta-LG were
      found using PCR-RFLP of genomic DNA. Rsa1 restriction enzyme digestion of a 120
      bp PCR fragment of exon 2 of beta-LG revealed two genetic variants, A (0.37) and
      B (0.63), and the three genotypes AA (0.175), AB (0.389), and BB (0.436). The
      differences in allelic frequency were not significant across the breeds,
      irrespective of their geographic origin and utility (chi(2) test, P > 0.05). The
      pattern of occurrence of allelic variants revealed that the B allele was more
      frequent in the majority of the Indian breeds than in breeds reported from
      countries of Southwest Asia, Eastern and Central Europe, and the Mediterranean. A
      higher level of heterozygosity (0.422) was discerned, despite the declining
      status of several of the Indian breeds. These findings revealed that Indian sheep
      are predominantly of the beta-LG B type.

PMID- 20052532
TI  - The reliability and criterion validity of the Diagnostic Infant and Preschool
      Assessment: a new diagnostic instrument for young children.
AB  - The need to assess Diagnostic and Statistical Manual, Fourth Edition (DSM-IV)
      disorders in children younger than 7 years of age has intensified as clinical
      efforts to diagnose and treat this population have increased, and clinical
      research on psychopathology has advanced. A new diagnostic instrument for young
      children was created, the Diagnostic Infant Preschool Assessment (DIPA), and was
      tested for test-retest reliability and concurrent criterion validity. The
      caregivers of 50 outpatients aged 1-6 years were interviewed twice by trained
      interviewers, once by a clinician and once by a research assistant, about eight
      disorders. The median test-retest intraclass correlation was 0.69, mean 0.61, and
      values ranged from 0.24 to 0.87. The median test-retest kappa was 0.53, mean
      0.52, and values ranged from 0.38 to 0.66. There were no differences by duration
      between interviews. Concurrent criterion validity show good agreement between the
      instrument and DSM-based Child Behavior Checklist scales when the DSM-based
      scales were matched well to the disorder (attention-deficit/hyperactivity
      inattentive and hyperactive and oppositional disorders). Preliminary data support
      the DIPA as a reliable and valid measure of symptoms in research and clinical
      work with very young children. This measure adds a tool that is flexible in
      covering both DSM-IV syndromes and empirically-validated developmental
      modifications that can help increase confidence in assessing young children,
      ensuring coverage of symptoms, and improve access to care.

PMID- 20052533
TI  - No association between SOD2 Val16Ala polymorphism and breast cancer
      susceptibility: a meta-analysis based on 9,710 cases and 11,041 controls.
AB  - Breast cancer is the most common cancer in women worldwide, but its etiology is
      still unclear. It is believed that oxidative stress plays an essential role in
      the development of breast cancer, while SOD2 is one of the primary enzymes that
      directly convert potential harmful oxidizing species to harmless metabolites. The
      association of SOD2 Val16Ala polymorphism and breast cancer risk has been widely
      reported, but results of previous studies were somewhat contradictory and
      underpowered. To overcome the limitations of individual study and to understand
      the real situation, we conducted a systematic review and meta-analysis toward the
      association between SOD2 Val16Ala polymorphism and breast cancer. Through
      retrieving MEDLINE, PubMed, Embase, and Web of Science, a total of 17 studies
      with 9,710 cases and 11,041 controls were identified. The results showed that no
      significant associations were found for the allele contrast (allele Ala vs.
      allele Val: OR = 1.020, 95% CI = 0.979-1.062), additive genetic model (Ala/Ala
      vs. Val/Val: OR = 1.091, 95% CI = 0.969-1.229), dominant genetic model (Ala/Ala
      +Ala/Val vs. Val/Val: OR = 1.045, 95% CI = 0.961-1.136), and recessive genetic
      model (Ala/Ala vs. Val/Val +Ala/Val: OR = 1.027, 95% CI = 0.956-1.102). In the
      stratified analysis by ethnicity and menopausal status, significant associations
      were also not detected in all genetic models. Conclusively, this meta-analysis
      strongly suggests that SOD2 Val16Ala polymorphism is not associated with breast
      cancer susceptibility.

PMID- 20052534
TI  - The fog hasn't lifted on "chemobrain" yet: ongoing uncertainty regarding the
      effects of chemotherapy and breast cancer on cognition.

PMID- 20052535
TI  - Lack of significant association between CYP1A1 T3801C polymorphism and breast
      cancer risk: a meta-analysis involving 25,087 subjects.
AB  - Breast cancer is the most prevalent cancer in the world, which is a major public
      health challenge. To date, many publications have evaluated the correlation
      between cytochrome P450 1A1 (CYP1A1) T3801C 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. By
      searching Medline, PubMed, and ISI Web of Knowledge databases, 23 studies
      including 10,520 cases and 14,567 controls were collected for CYP1A1 T3801C
      polymorphism. The strength of association between CYP1A1 T3801C polymorphism and
      breast cancer risk was assessed by calculating crude ORs with 95% CIs. The pooled
      ORs were performed for codominant model, dominant model, and recessive model,
      respectively. Overall, no significant associations between CYP1A1 T3801C
      polymorphism and breast cancer susceptibility were found for TT versus CC (OR =
      0.93; 95% CI: 0.72-1.19), TC versus CC (OR = 0.95; 95% CI: 0.79-1.14), TT + TC
      versus CC (OR = 0.93; 95% CI: 0.75-1.15), and TT versus TC + CC (OR = 0.99; 95%
      CI: 0.87-1.13). In the stratified analysis by ethnicity, menopausal status, and
      source of controls, no significant associations were detected in all genetic
      models. In conclusion, this meta-analysis provides strong evidence that CYP1A1
      T3801C polymorphism is not associated with breast cancer risk.

PMID- 20052536
TI  - 17beta-estradiol enhances alpha(5) integrin subunit gene expression through
      ERalpha-Sp1 interaction and reduces cell motility and invasion of ERalpha
      positive breast cancer cells.
AB  - In breast tumors the expression of estrogen receptor alpha (ERalpha) is known to
      be associated with a more favorable prognosis. ERalpha expression has been
      reported to reduce the metastatic potential of breast cancer cells. Recently, we
      have observed that extracellular matrix proteins activate ERalpha and that both
      liganded and unliganded receptor modulate cell invasiveness acting at nuclear
      level. To explain the mechanisms by which ERalpha regulates cell adhesion, we
      have evaluated the expression of alpha(5)beta(1) integrin, prevalently expressed
      in stationary cells, in response to 17beta-estradiol (E2). Here we show that
      E2/ERalpha increases the expression of integrin alpha(5)beta(1) through Sp1
      mediated binding to a GC-rich region located upstream of an ERE half-site in the
      5' flanking region of the alpha(5) gene forming a ternary ERalpha-Sp1-DNA
      complex. Estrogen responsiveness of the alpha(5) gene promoter, as observed in
      HeLa cells, underlies a general mechanism of regulation which is not strictly
      linked to the cell type. Our data reveal novel insight into the molecular
      mechanisms sustaining the reduced invasiveness of ERalpha expressing cells
      demonstrating that alpha(5)beta(1) integrin expression is related to the
      maintenance of the stationary status of the cells, counteracting E2/ERalpha
      capability to enhance breast cancer cell migration and invasion.

PMID- 20052537
TI  - Correlation between consanguineous marriages and age-standardized mortality rate
      due to breast cancer, an ecologic study.

PMID- 20052538
TI  - Orally administered endoxifen is a new therapeutic agent for breast cancer.
AB  - Endoxifen is the key active metabolite of tamoxifen, a widely used breast cancer
      drug. Orally administered tamoxifen, is extensively metabolized by cytochrome
      P450 (CYP) enzymes, namely CYP3A4 and CYP2D6, into active metabolites, especially
      endoxifen. Due to genetic polymorphism of CYP2D6, significant numbers of women
      metabolize tamoxifen to varying degree and may not receive the optimal benefit
      from tamoxifen treatment. We show that oral administration of endoxifen achieved
      the optimally effective systemic levels reliably, which may eliminate variability
      associated with tamoxifen metabolism that leads to unpredictability in efficacy.
      Furthermore, use of endoxifen may avoid a potential serious drug interaction
      found between tamoxifen and commonly used selective serotonin reuptake
      inhibitors, antidepressants. Endoxifen was active in inhibiting the growth of
      various breast tumor cell lines in NCI 60-Cell Line Screen. Orally administered
      endoxifen is rapidly absorbed and systemically available when tested in female
      rats. The endoxifen-treated rats showed 787% higher exposure (AUC(0-infinity))
      and 1,500% higher concentration (C (max)) levels of endoxifen when compared with
      tamoxifen. Oral endoxifen administration once a day for 28 consecutive days at
      dosages 2, 4, and 8 mg/kg proved safe and resulted in progressive inhibition of
      the growth of the human mammary tumor xenografts in female mice. This is the
      first ever in vivo report on endoxifen as a potentially new therapeutic agent for
      breast cancer.

PMID- 20052539
TI  - Breast cancer survival in women of African descent living in the US and in the
      Caribbean: effect of place of birth.
AB  - In order to shed light on genetic and environmental factors contributing to
      breast cancer health disparities, anonymous data from the cancer registry in
      Brooklyn, NY and two countries in the Caribbean, have been analyzed and compared.
      De-identified data were obtained on 3,710 women from three cancer registries in
      Brooklyn (New York), Guyana, and Trinidad, all having been diagnosed with breast
      cancer between 1995 and 2007, with follow-up through to early 2009. There was a
      significant difference in breast cancer survival according to race, place of
      birth, and place of residence. Women of African origin had a significantly worse
      survival than White women. Women born in the Caribbean had significantly worse
      survival in comparison to their counterpart born in the US, independently from
      their ethnic background (adjusted hazard ratio: 1.6; 95% CI: 1.2-2.1). A
      significant lower breast cancer survival was observed in African Caribbean women
      living in the Caribbean (HR: 1.8; 95% CI: 1.6-2.1) versus African-Caribbean women
      born in the Caribbean and living in the US (HR: 1.3; 95% CI 1.1-1.7), versus
      African-descent women born and living in the US. This study suggests that
      biological, behavioral, environmental, and clinical factors play a significant
      role in the observed difference in breast cancer outcome in women of Afro
      Caribbean descent.

PMID- 20052540
TI  - Association between CYP19 polymorphisms and breast cancer risk: results from
      10,592 cases and 11,720 controls.
AB  - The association of CYP19 gene polymorphisms with breast cancer has been widely
      reported, but results of previous studies were somewhat contradictory and
      underpowered. In order to overcome the limitations of individual study and to
      understand the real situation, we conducted a systematic review and meta-analysis
      including three CYP19 gene polymorphisms [R264C polymorphism, CYP19_630 3-bp
      del/Ins polymorphism, and CYP19_681 (TTTA)(n) polymorphisms]. A total of 22
      studies with 10,592 cases and 11,720 controls were identified, and the results
      showed that R264C polymorphism was not associated with breast cancer risk in
      overall (T vs. C: OR = 1.061, 95% CI = 0.929-1.212) or race-based populations (T
      vs. C for Asian: OR = 1.169, 95% CI = 1.002-1.363; for Caucasian: OR = 0.787, 95%
      CI = 0.597-1.037); meanwhile, for Asian individuals, 3-bpDel/Ins polymorphism
      showed a significantly association with breast cancer susceptibility (for allele
      Del vs. allele Ins: OR = 1.278, 95% CI = 1.066-1.532) while the carriers of
      allele (TTTA)(12) can significantly decrease breast cancer risk (OR = 0.752, 95%
      CI = 0.603-0.939). Furthermore, the carriers of allele (TTTA)(10) were
      significantly associated with breast cancer susceptibility (OR = 1.515, 95% CI =
      1.115-2.058). It can be concluded that potentially functional CYP19_630 3-bp
      del/Ins polymorphism and CYP19_681 (TTTA)(n) polymorphisms may play a low
      penetrance role in breast cancer susceptibility in an ethnicity-specific manner.

PMID- 20052542
TI  - Bioaccumulation of microcystin and its oxidative stress in the apple (Malus
      pumila).
AB  - The bioaccumulation and harmful effects of microcystins (MCs) and the activity of
      peroxidase (POD) and superoxide dismutase (SOD) were examined in the apple (Malus
      pumila) exposed in vitro with the crude extract of toxic cyanobacterial blooms
      from Dianchi Lake in southwestern China. The results showed that the growth and
      proliferation of M. pumila shoots in vitro decreased markedly after exposure to
      microcystins above 0.3 microg/ml. Recovered microcystins determined by enzyme
      linked immunosorbent assay (ELISA) in M. pumila shoot cultures increased with
      exposure time and concentration. After 14 days exposure to the concentration of 3
      microg/ml microcystins, M. pumila shoot cultures accumulated microcystins up to a
      concentration of 510.23 +/- 141.10 ng MC-LR equiv/g FW (fresh weight), equivalent
      to an accumulation rate of 36.45 ng/g day. POD activity was significantly
      increased after 7 days exposure to 3 microg/ml microcystins. After 14 days of
      exposure, microcystins caused POD to increase significantly at the concentration
      of 0.3 and 3 microg/ml. The activity of SOD was not affected by microcystins at
      concentrations up to 3 microg/ml on 7 days. After 14 days exposure to
      microcystins, SOD activity increased significantly at the concentration of 0.3
      and 3 microg/ml in M. pumila shoot cultures.

PMID- 20052543
TI  - Renal biopsy findings in Iran: case series report from a referral kidney center.
AB  - BACKGROUND: Several registries and single centers have reported the results of
      their renal biopsies from different parts of the world. As there are only few
      data regarding the epidemiology of glomerulonephritides in Iran, this study was
      conducted to determine the results of renal biopsy findings during the last 10
      years in our center. METHODS: Data from 1,436 patients who had undergone a renal
      biopsy in our center between 1998 and 2007 were collected retrospectively for the
      first 989 patients and prospectively for the rest of them, including demographic
      data, renal syndrome at presentation and laboratory findings. All kidney
      specimens were studied with light and immunofluorescent microscopies. RESULTS:
      Among 1,407 patients with a definite pathologic diagnosis, 1,052 (74.8%) had a
      primary glomerular disease, 241 (17.2%) had a secondary glomerular disease, 66
      (4.6%) had tubular disease, 19 (1.3%) had vascular disease and 7 (0.5%) had end
      stage kidney disease. The most frequent types of biopsy-proven renal diseases
      were membranous glomerulopathy (MG) (377 patients, 26.8%), IgA nephropathy (IgAN)
      (155 patients, 11%), lupus nephritis (155 patients, 11%), focal segmental
      glomerulosclerosis (141 patients, 10%) and minimal change disease (117 patients,
      8.3%). The predominant presentation was nephrotic syndrome in almost all cases,
      with the exception of chronic glomerulonephritis, acute tubular necrosis and
      acute tubulointerstitial nephritis. The epidemiology of our renal biopsy findings
      was similar to reports from most European countries and United Arab Emirates, but
      different from many other neighboring countries, North America and Far East.
      CONCLUSIONS: In our report of 1,407 renal biopsy specimens, MG and IgAN were the
      most frequent biopsy-proven renal diseases. FSGS was the third cause of primary
      glomerular disease, and lupus nephritis was the most common secondary glomerular
      disease. The unusually high frequency of presentation as nephrotic syndrome may
      be due to referral nature of our center and less liberal indications for renal
      biopsy.

PMID- 20052544
TI  - Four-year enterprise PACS support trend analysis.
AB  - While health care facilities recognize the need for dedicated picture archiving
      and communication system (PACS) staff at the time of the initial implementation
      of PACS, they often do not plan accordingly for ongoing or increasing PACS
      support needs as a PACS matures. This article reviews trends in a health care
      system's PACS support data over 4 years to show how PACS support needs evolve
      over time. PACS support items were logged and categorized over this period and
      were used by the health care system to become more proactive in system support
      and adjust staffing levels accordingly. This article details how PACS support
      needs change over the life of a PACS installation and can be used as a model for
      health care facilities planning for future PACS support needs.

PMID- 20052545
TI  - Effects of spiritual well-being on subsequent happiness, psychological well
      being, and stress.
AB  - Recently, Gomez and Fisher (Gomez R and Fisher JW (2003) Pers Individ Dif 35:
      1975-1991) proposed that four facets of spiritual well-being exist, namely,
      personal, communal, environmental, and transcendental spiritual well-being. Based
      on data from three independent studies, the present research effort tested the
      validity of a German version of (Gomez R and Fisher JW (2003) Pers Individ Dif
      35: 1975-1991) of the Spiritual Well-Being Questionnaire (SWBQ-G). It was found
      that the SWBQ-G was factorially valid and that each of the four SWBQ-G scales was
      discriminant to mental, physical, and emotional well-being. Also, it was found
      that the SWBQ-G predicted levels of subsequent happiness, psychological well
      being (positive relationship), and stress (negative relationship). These results
      add to our knowledge about the validity of the construct of spiritual well-being.

PMID- 20052546
TI  - Hunter syndrome in an 11-year old girl on enzyme replacement therapy with
      idursulfase: brain magnetic resonance imaging features and evolution.
AB  - Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive
      disorder. Affected females are extremely rare, mostly due to skewed X chromosome
      inactivation. A few papers outline MPS-II brain magnetic resonance imaging (MRI)
      "gestalt" in males, but neuroradiological reports on females are still lacking.
      We present an 11-year-old girl affected by the severe form of MPS-II who was
      followed up over a time span of 8 years, focusing on clinical and brain MRI
      evolution. In the last 2.5 years, the patient has been treated with enzyme
      replacement therapy (ERT) with idursulfase (ElapraseTM, Shire Human Genetic
      Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in
      our patient did not differ from those detected in male patients: J-shaped
      pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2
      hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild
      odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT
      introduction, whereas perivascular space enlargement did not change significantly
      before and after ERT. Cognitive impairment worsened independently from the course
      of white matter abnormality. Despite a profound knowledge of genetic and
      biochemical aspects in MPS-II, neuroradiology is still poorly characterized,
      especially in female patients. Spinal and brain involvement and its natural
      course and evolution after ERT introduction still need to be clarified.

PMID- 20052547
TI  - A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy.
AB  - BACKGROUND: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare
      disorder of GABA catabolism, with only a single sibship reported. We report on a
      third case, a Japanese female infant with severe psychomotor retardation and
      recurrent episodic lethargy with intractable seizures, with the diagnosis
      facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS). METHODS:
      Neuroimaging was performed at the first episode of lethargy. For (1)H-MRS,
      locations were placed in the semioval center and the basal ganglia.
      Quantification of metabolite concentrations were derived using the LCModel. We
      confirmed the diagnosis subsequently by enzyme and molecular studies, which
      involved direct DNA sequence analysis and the development of a novel multiplex
      ligation-dependent probe amplification test. RESULTS: (1)H-MRS analysis revealed
      an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the
      results of quantitative (1)H-MRS and clinical findings, GABA-T deficiency was
      suspected and confirmed in cultured lymphoblasts. Molecular studies of the GABA-T
      gene revealed compound heterozygosity for a deletion of one exon and a missense
      mutation, 275G>A, which was not detected in 210 control chromosomes. CONCLUSIONS:
      Our results suggest that excessive prenatal GABA exposure in the central nervous
      system (CNS) was responsible for the clinical manifestations of GABA transaminase
      deficiency. Our findings suggest the dual nature of GABA as an excitatory
      molecule early in life, followed by a functional switch to an inhibitory species
      later in development. Furthermore, quantitative (1)H-MRS appears to be a useful,
      noninvasive tool for detecting inborn errors of GABA metabolism in the CNS.

PMID- 20052548
TI  - The monitoring of trace elements in blood samples from patients with inborn
      errors of metabolism.
AB  - Patients having inborn errors of intermediary metabolism (IEMs) may have element
      deficiencies related to dietary treatment. Our objective was to study several
      elements [cobalt (Co), copper (Cu), zinc (Zn), selenium (Se), manganese (Mn),
      molybdenum (Mo) and magnesium (Mg)] in patients with IEMs with and without
      dietary treatment and to compare these results with those established in a
      healthy paediatric population. We studied 72 patients with IEMs (age range 2
      months-44 years; median 10.5 years), with and without protein-restricted dietary
      treatment. Control values were established in 92 subjects (age range 1 day-42
      years; median 6.5 years). Dietary treatment consisted of a natural protein
      restricted diet supplemented with a special formula, depending on the specific
      metabolic defect. Samples were analysed with an Agilent 7500ce-ICP mass
      spectrometer. Significant differences were observed when we compared patients
      under dietary treatment and control values for Se and Co (P < 0.0001). No
      differences were observed for the other elements when the different groups were
      compared, except for Co (IEM patients without dietary treatment vs control group;
      P = 0.003). For Se and cobalamin, the daily intake of our patients (Se 48 +/- 16
      ug/day; cobalamin 3.5 ug/day) was slightly higher than the recommended daily
      averages (RDAs) (40 ug/day and 1.8 ug/day, respectively). We concluded that IEM
      patients under dietary treatment showed significantly lower selenium values in
      spite of correct supplementation, reinforcing the idea that these patients should
      be regularly monitored, at least for this element. Further investigations seem
      advisable about Se and Co availability in special diets.

PMID- 20052549
TI  - Effect of Spinacia oleraceae L. and Perilla frutescens L. on antioxidants and
      lipid peroxidation in an intervention study in healthy individuals.
AB  - Daily consumption of fruits and vegetables is frequently recommended to prevent
      several diseases. This health-promoting effect is considered to be in part due to
      the antioxidant content of fruits and vegetables and their ability to decrease
      oxidative stress. To investigate whether the ingestion of preparations from
      spinach or perilla, two carotenoid-rich leafy vegetables, is followed by an
      increase in carotenoid concentration and/or affects parameters of oxidative
      stress in human blood plasma. 12 healthy volunteers ingested a perilla- or
      spinach preparation for 10 days (5 mg lutein/d). We quantified antioxidant levels
      in plasma, kinetics of lipid peroxidation, MDA concentration, and total
      antioxidative capacity of plasma. We observed a significant increase in lutein
      content and a moderate increase (n.s.) in beta-carotene content in human blood
      plasma after consumption of spinach or perilla. The markers of lipid peroxidation
      tended to decrease, but no influence on antioxidative capacity of plasma could be
      detected. The high lutein content of perilla caused a more pronounced increase of
      lutein compared to spinach. Both vegetables seem to be able to influence lipid
      peroxidation in a beneficial manner.

PMID- 20052551
TI  - Effect of transsphenoidal surgery on decreased visual acuity caused by pituitary
      apoplexy.
AB  - We treated 12 patients with pituitary apoplexy out of 103 patients with pituitary
      tumors from August 1994 to March 2008 in the Nishi-Kobe Medical Center. The male
      to female ratio was 1:2 and the average age was 43 years old, ranging from 19 to
      73. The symptoms on presentation were a decrease of visual acuity in nine,
      headache in seven, endocrinological disturbance in six, visual field defect in
      seven, a febrile state in six, vomiting in four, oculomotor disturbance in two,
      abducens palsy in one, and transient altered consciousness in one. All patients
      underwent transsphenoidal surgery and, in four of these, surgery was conducted
      within 7 days after onset. All nine patients with a decrease in the visual acuity
      recovered (100%) and, in addition, complete or near-complete vision recovery was
      noted in six out of eight patients (75%), excluding one patient whom we were
      unable to examine accurately. Emergent surgery was performed for only two
      patients with an acute deterioration of the visual acuity, with one finally
      developing complete blindness. Based on this study, we conclude that
      decompressive surgery is very useful for decreased visual acuity caused by
      pituitary apoplexy, but it is not necessary to perform emergent surgery for
      pituitary apoplexy in the absence of severe visual deterioration.

PMID- 20052552
TI  - HLA-G expression in human breast cancer: implications for diagnosis and
      prognosis, and effect on allocytotoxic lymphocyte response after hormone
      treatment in vitro.
AB  - OBJECTIVE: The aim of this study is to investigate clinical implications of human
      leukocyte antigen-G (HLA-G) expression in breast cancer. METHODS: HLA-G
      expression in 235 primary breast cancer tissues was investigated using
      immunohistochemistry, and plasma soluble HLA-G (sHLA-G) was measured in 44 breast
      cancer patients using a specific HLA-G enzyme-linked immunosorbent assay (ELISA).
      Effects of estradiol/progesterone and their antagonists tamoxifen/RU486 on HLA-G
      expression in cultured breast cancer MCF-7 cells were determined by real-time
      polymerase chain reaction (PCR) and the ELISA. Alterations of HLA-G expression by
      the hormone treatments on subsequent allocytotoxic lymphocyte (allo-CTL) response
      were also examined. RESULTS: In the study, approximately 66% of neoplasm lesions
      were identified to have positive HLA-G expression. This expression was
      significantly correlated with tumor size, nodal status, and clinical disease
      stage (P = 0.0001, 0.012, and 0.0001, respectively). Patients with positive HLA-G
      expression had a lower survival rate than those with negative expression (P <
      0.028). Plasma sHLA-G levels were significantly higher in breast cancer patients
      than in healthy controls (P < 0.001), with the area under the receiver-operating
      characteristic (ROC) curve being 0.95. HLA-G expression in breast cancer MCF-7
      cells was enhanced by estradiol/progesterone but reduced by their antagonists.
      Cytotoxicity studies showed that allo-CTL response in MCF-7 cells was inhibited
      by prior treatment with estradiol/progesterone, but was amplified by their
      antagonists. The effects could be restored or further strengthened by the
      addition of anti-HLA-G antibodies. CONCLUSION: Our findings suggest that HLA-G
      may have potential clinical implications in diagnosis, prognosis, and
      immunotherapy of patients with breast cancer.

PMID- 20052553
TI  - Tumor marker evolution: comparison with imaging for assessment of response to
      chemotherapy in patients with colorectal liver metastases.
AB  - BACKGROUND: As the real clinical significance of carcinoembryonic antigen (CEA)
      and carbohydrate antigen 19.9 (CA19.9) evolution during preoperative chemotherapy
      for colorectal liver metastases (CLM) is still unknown, we explored the
      correlation between biological and radiological response to chemotherapy, and
      their comparative impact on outcome after hepatectomy. METHODS: All patients
      resected for CLM at our hospital between 1990 and 2004 with the following
      eligibility criteria were included in the study: (1) preoperative chemotherapy,
      (2) complete resection of CLM, (3) no extrahepatic disease, and (4) elevated
      baseline tumor marker values. A 20% change of tumor marker levels while on
      chemotherapy was used to define biological response (decrease) or progression
      (increase). Correlation between biological and radiological response at computed
      tomography (CT) scan, and their impact on overall survival (OS) and progression
      free survival (PFS) after hepatectomy were determined. RESULTS: Among 119 of 695
      consecutive patients resected for CLM who fulfilled the inclusion criteria,
      serial CEA and CA19.9 were available in 113 and 68 patients, respectively. Of
      patients with radiological response or stabilization, 94% had similar biological
      evolution for CEA and 91% for CA19.9. In patients with radiological progression,
      similar biological evolution was observed in 95% of cases for CEA and in 64% for
      CA19.9. On multivariate analysis, radiological response (but not biological
      evolution) independently predicted OS. However, progression of CA19.9, but not
      radiological response, was an independent predictor of PFS. CONCLUSIONS: In
      patients with CLM and elevated tumor markers, biological response is as accurate
      as CT imaging to assess "clinical" response to chemotherapy. With regards to PFS,
      CA19.9 evolution has even better prognostic value than does radiological
      response. Assessment of tumor markers could be sufficient to evaluate
      chemotherapy response in a nonsurgical setting, limiting the need of repeat
      imaging.

PMID- 20052554
TI  - Artemisioside, a new monoterpene glucoside from the aerial parts of Artemisia
      ordosica (Asteraceae).
AB  - A new monoterpene glucoside, artemisioside, was isolated from the aerial parts of
      Artemisia ordosica Krasch. (Asteraceae). The chemical structure was elucidated
      from physicochemical data and by the application of Klyne's rule.

PMID- 20052555
TI  - Flow pumping system for physiological waveforms.
AB  - A pulsatile flow pumping system is developed to replicate flow waveforms with
      reasonable accuracy for experiments simulating physiological blood flows at
      numerous points in the body. The system divides the task of flow waveform
      generation between two pumps: a gear pump generates the mean component and a
      piston pump generates the oscillatory component. The system is driven by two
      programmable servo controllers. The frequency response of the system is used to
      characterize its operation. The system has been successfully tested in vascular
      flow experiments where sinusoidal, carotid, and coronary flow waveforms are
      replicated.

PMID- 20052556
TI  - Fast set-up asynchronous brain-switch based on detection of foot motor imagery in
      1-channel EEG.
AB  - Bringing a Brain-Computer Interface (BCI) out of the lab one of the main problems
      has to be solved: to shorten the training time. Finding a solution for this
      problem, the use of a BCI will be open not only for people who have no choice,
      e.g., persons in a locked-in state, or suffering from a degenerating nerve
      disease. By reducing the training time to a minimum, also healthy persons will
      make use of the system, e.g., for using this kind of control for games. For
      realizing such a control, the post-movement beta rebound occurring after brisk
      feet movement was used to set up a classifier. This classifier was then used in a
      cue-based motor imagery system. After classifier adaptation, a self-paced brain
      switch based on brisk foot motor imagery (MI) was evaluated. Four out of six
      subjects showed that a post-movement beta rebound after feet MI and succeeded
      with a true positive rate between 69 and 89%, while the positive predictive value
      was between 75 and 93%.

PMID- 20052557
TI  - Studying genetic code by a matrix approach.
AB  - Following Petoukhov and his collaborators, we use two length n zero-one
      sequences, alpha and beta, to represent a length n genetic sequence (alpha/beta)
      so that the columns of (alpha/beta) have the following correspondence with the
      nucleotides: C ~ (0/0), U ~ (1/0), G ~ (1/1), A ~ (0/1). Using the Gray code
      ordering to arrange alpha and beta, we build a 2(n) x 2(n) matrix C(n) including
      all the 4(n) length n genetic sequences. Furthermore, we use the Hamming distance
      of alpha and beta to construct a 2(n) x 2(n) matrix D(n). We explore structures
      of these matrices, refine the results in earlier papers, and propose new
      directions for further research.

PMID- 20052558
TI  - A cell-based model of endothelial cell migration, proliferation and maturation
      during corneal angiogenesis.
AB  - The motivation of this work stems from two critical experimental observations
      associated with corneal angiogenesis: (1) angiogenesis will not succeed without
      endothelial cell proliferation, and (2) proliferation mainly occurs at the
      leading edge of developing sprouts (Sholley et al., Lab. Invest. 51:624-634,
      1984). To discover the underlying mechanisms of these phenomena, we develop a
      cell-based mathematical model that integrates a mechanical model of elongation
      with a biochemical model of cell phenotype variation regulated by angiopoietins
      within a developing sprout. This model allows for a detailed study of the
      relative roles of endothelial cell migration, proliferation, and maturation. The
      model is validated by quantitatively comparing its predictions with data derived
      from corneal angiogenesis experiments. We conclude that cell elasticity and cell
      to-cell adhesion allow only limited sprout extension in the absence of
      proliferation, and the maturation process combined with bioavailability of VEGF
      can explain the localization of proliferation to the leading edge. We also use
      this model to investigate the effects of X-ray irradiation, Ang-2 inhibition, and
      extracellular matrix anisotropy on sprout morphology and extension.

PMID- 20052560
TI  - Oximetry alone versus portable polygraphy for sleep apnea screening before
      bariatric surgery.
AB  - BACKGROUND: Screening for obstructive sleep apnea (OSA) is recommended as part of
      the preoperative assessment of obese patients scheduled for bariatric surgery.
      The objective of this study was to compare the sensitivity of oximetry alone
      versus portable polygraphy in the preoperative screening for OSA. METHODS:
      Polygraphy (type III portable monitor) and oximetry data recorded as part of the
      preoperative assessment before bariatric surgery from 68 consecutive patients
      were reviewed. We compared the sensitivity of 3% or 4% desaturation index
      (oximetry alone) with the apnea-hypopnea index (AHI; polygraphy) to diagnose OSA
      and classify the patients as normal (<10 events per hour), mild to moderate (10
      30 events per hour), or severe (>30 events per hour). RESULTS: Using AHI, the
      prevalence of OSA (AHI > 10 per hour) was 57.4%: 16.2% of the patients were
      classified as severe, 41.2% as mild to moderate, and 42.6% as normal. Using 3%
      desaturation index, 22.1% were classified as severe, 47.1% as mild to moderate,
      and 30.9% as normal. With 4% desaturation index, 17.6% were classified as severe,
      32.4% as mild, and 50% as normal. Overall, 3% desaturation index compared to AHI
      yielded a 95% negative predictive value to rule out OSA (AHI > 10 per hour) and a
      100% sensitivity (0.73 positive predictive value) to detect severe OSA (AHI > 30
      per hour). CONCLUSIONS: Using oximetry with 3% desaturation index as a screening
      tool for OSA could allow us to rule out significant OSA in almost a third of the
      patients and to detect patients with severe OSA. This cheap and widely available
      technique could accelerate preoperative work-up of these patients.

PMID- 20052559
TI  - An update of controlled physical activity trials in cancer survivors: a
      systematic review and meta-analysis.
AB  - INTRODUCTION: Approximately 11.1 million cancer survivors are alive in the United
      States. Activity prescriptions for cancer survivors rely on evidence as to
      whether exercise during or after treatment results in improved health outcomes.
      This systematic review and meta-analysis evaluates the extent to which physical
      activity during and post treatment is appropriate and effective across the cancer
      control continuum. METHODS: A systematic quantitative review of the English
      language scientific literature searched controlled trials of physical activity
      interventions in cancer survivors during and post treatment. Data from 82 studies
      were abstracted, weighted mean effect sizes (WMES) were calculated from 66 high
      quality studies, and a systematic level of evidence criteria was applied to
      evaluate 60 outcomes. Reports of adverse events were abstracted from all studies.
      RESULTS: Quantitative evidence shows a large effect of physical activity
      interventions post treatment on upper and lower body strength (WMES = 0.99 &
      0.90, p < 0.0001 & 0.024, respectively) and moderate effects on fatigue and
      breast cancer-specific concerns (WMES = -0.54 & 0.62, p = 0.003 & 0.003,
      respectively). A small to moderate positive effect of physical activity during
      treatment was seen for physical activity level, aerobic fitness, muscular
      strength, functional quality of life, anxiety, and self-esteem. With few
      exceptions, exercise was well tolerated during and post treatment without adverse
      events. CONCLUSIONS: Current evidence suggests many health benefits from physical
      activity during and post cancer treatments. Additional studies are needed in
      cancer diagnoses other than breast and with a focus on survivors in greatest need
      of improvements for the health outcomes of interest.

PMID- 20052561
TI  - Racial, socioeconomic, and rural-urban disparities in obesity-related bariatric
      surgery.
AB  - BACKGROUND: Morbid obesity is associated with serious health and social
      consequences, high medical costs and is increasing in the USA, particularly among
      rural, socioeconomically disadvantaged populations. Bariatric surgery more often
      provides significant long-term weight loss than traditional weight loss
      treatments. We examined the likelihood of bariatric surgery among morbidly obese
      patients across rural/urban locales, racial/ethnic groups, insurance categories,
      socioeconomic, and comorbidity levels. METHODS: We examined 159,116 records
      representing 774,000 patients with morbid obesity from the 2006 Nationwide
      Inpatient Sample. We determined the likelihood, expressed in odds ratios, of
      bariatric surgery associated with each patient characteristic using survey
      weighted univariate logistic regression. We also performed multivariate logistic
      regression, assuming all patient factors were independent. RESULTS: After
      adjusting for patient-level characteristics, the most rural residents were 23%
      less likely to receive bariatric surgery than urban residents. Other demographic
      features associated with significantly lower odds ratios for bariatric surgery
      included minority status, male gender, lower income, older age, non-private
      insurance status, and higher comorbidity. Rural-dwelling patients who are non
      white, male, poorer, older, sicker, and non-privately insured almost never
      received bariatric surgery (OR = 0.0089). CONCLUSIONS: Though obesity is more
      prevalent among middle-aged, rural, economically disadvantaged, and racial/ethnic
      minority populations, these patients are unlikely to access bariatric surgery.
      Because obesity is a leading cause of preventable morbidity and mortality in the
      USA, effective treatments should be made available to all patients who might
      benefit. Current Medicare/Medicaid policies that reimburse only high volume
      centers may effectively deny rural residents who rely on these insurance programs
      for bariatric surgery.

PMID- 20052562
TI  - Identification of a potential molecular link between the glucocorticoid and
      serotonergic signaling systems.
AB  - Glucocorticoid receptor (GR) and serotonin (5-hydroxytryptamine (5-HT)) signaling
      systems play a pivotal role in the regulation of the hypothalamic-pituitary
      adrenal (HPA) axis, but the molecular nature of interactions between these two
      systems remain largely unidentified. We used computational and experimental
      approaches to evaluate if DNA-protein interactions would provide a molecular link
      for the interaction between 5-HT and GR systems. Bioinformatic analysis
      identified nine binding sites in various serotonin receptors (HTR1D, HTR1F,
      HTR2A, HTR3A, and HTR6) for transcription factors in the GR family.
      Electrophoretic mobility shift assays (EMSA) using HeLa nuclear extract and
      purified full-length GR verified most of the predicted DNA-protein interactions.
      Six binding sites verified by EMSA results were evolutionarily conserved in
      multiple species. Multiple lines of evidence from computational and experimental
      analyses in this study support the potential of a molecular link between 5-HT and
      GR signaling systems. This finding provides new approaches to studies directed at
      mechanisms for glucocorticoid negative feedback regulation of the HPA axis
      involving 5-HT and interventional studies directed to neuropsychiatric diseases.

PMID- 20052563
TI  - Gastric carcinoma--a big challenge in a poor economy.
AB  - BACKGROUND: Gastric carcinoma is usually characterized with significant morbidity
      and mortality mainly because of late presentation. Late presentation of gastric
      carcinoma is a prominent feature in developing and poor countries. AIM OF STUDY:
      The purpose of this study is to present our experience with the pattern and
      outcome of gastric tumors at the University of Benin Teaching Hospital, Benin
      City, Nigeria; with emphasis on late presentation of the patients. PATIENTS AND
      METHODS: The case files of the patients that were managed at the University of
      Benin Teaching Hospital for gastric tumors over a 5-year period (January 2004 to
      December 2006) were analyzed for biodata, symptoms and signs of disease, findings
      at operation, treatment offered, and outcome of treatment. RESULTS: The
      male/female ratio was 2.3:1, with the youngest patient being 38 years while the
      oldest patient was 76 years old. Upper abdominal pain and a palpable mass per
      abdomen were the commonest symptoms and signs, respectively. Alcohol ingestion
      was the commonest identifiable risk factor. Only 30.4% of the patients presented
      within a year of the onset of symptoms. The gastric antrum was affected in over
      78% of the cases, and adenocarcinoma was found in about 90% of the patients.
      Partial gastrectomy with gastrojejunostomy was the commonest procedure carried
      out. The mortality rate was 39.1%, and of the patients that died, 66.7% occurred
      within a year from time of diagnosis. CONCLUSION: Most of the cases of gastric
      carcinoma presented in this study presented late with associated significant
      mortality. Health education is advised with a view to encouraging early
      presentation.

PMID- 20052566
TI  - Computer-assisted instruction to prevent early reading difficulties in students
      at risk for dyslexia: Outcomes from two instructional approaches.
AB  - The relative effectiveness of two computer-assisted instructional programs
      designed to provide instruction and practice in foundational reading skills was
      examined. First-grade students at risk for reading disabilities received
      approximately 80 h of small-group instruction in four 50-min sessions per week
      from October through May. Approximately half of the instruction was delivered by
      specially trained teachers to prepare students for their work on the computer,
      and half was delivered by the computer programs. At the end of first grade, there
      were no differences in student reading performance between students assigned to
      the different intervention conditions, but the combined-intervention students
      performed significantly better than control students who had been exposed to
      their school's normal reading program. Significant differences were obtained for
      phonemic awareness, phonemic decoding, reading accuracy, rapid automatic naming,
      and reading comprehension. A follow-up test at the end of second grade showed a
      similar pattern of differences, although only differences in phonemic awareness,
      phonemic decoding, and rapid naming remained statistically reliable.

PMID- 20052564
TI  - DOC2B, C2 domains, and calcium: A tale of intricate interactions.
AB  - Ca(+2)-dependent exocytosis involves vesicle docking, priming, fusion, and
      recycling. This process is performed and regulated by a vast number of synaptic
      proteins and depends on proper protein-protein and protein-lipid interactions.
      Double C2 domain (DOC2) is a protein family of three isoforms found while
      screening DNA libraries with a C2 probe. DOC2 has three domains: the Munc13
      interacting domain and tandem C2s (designated C2A and C2B) connected by a short
      polar linker. The C2 domain binds phospholipids in a Ca(2+)-dependent manner.
      This review focuses on the ubiquitously expressed isoform DOC2B. Sequence
      alignment of the tandem C2 protein family in mouse revealed high homology (81%)
      between rabphilin-3A and DOC2B proteins. We created a structural model of DOC2B's
      C2A based on the crystal structure of rabphilin-3A with and without calcium and
      found that the calcium-binding loops of DOC2B move upon calcium binding, enabling
      efficient plasma membrane penetration of its C2A. Here, we discuss the potential
      relation between the DOC2B bioinformatical model and its function and suggest a
      possible working model for its interaction with other proteins of the exocytotic
      machinery, including Munc13, Munc18, and syntaxin.

PMID- 20052565
TI  - The pathogenic implication of abnormal interaction between apolipoprotein E
      isoforms, amyloid-beta peptides, and sulfatides in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the aging
      population. Prior work has shown that the epsilon4 allele of apolipoprotein E
      (apoE4) is a major risk factor for "sporadic" AD, which accounts for >99% of AD
      cases without a defined underlying mechanism. Recently, we have demonstrated that
      sulfatides are substantially and specifically depleted at the very early stage of
      AD. To identify the mechanism(s) of sulfatide loss concurrent with AD onset, we
      have found that: (1) sulfatides are specifically associated with apoE-associated
      particles in cerebrospinal fluid (CSF); (2) apoE modulates cellular sulfatide
      levels; and (3) the modulation of sulfatide content is apoE isoform dependent.
      These findings not only lead to identification of the potential mechanisms
      underlying sulfatide depletion at the earliest stages of AD but also serve as
      mechanistic links to explain the genetic association of apoE4 with AD. Moreover,
      our recent studies further demonstrated that (1) apoE mediates sulfatide
      depletion in amyloid-beta precursor protein transgenic mice; (2) sulfatides
      enhance amyloid beta (Abeta) peptides binding to apoE-associated particles; (3)
      Abeta42 content notably correlates with sulfatide content in CSF; (4) sulfatides
      markedly enhance the uptake of Abeta peptides; and (5) abnormal sulfatide
      facilitated Abeta uptake results in the accumulation of Abeta in lysosomes.
      Collectively, our studies clearly provide a link between apoE, Abeta, and
      sulfatides in AD and establish a foundation for the development of effective
      therapeutic interventions for AD.

PMID- 20052567
TI  - Do social activities substitute for food in youth?
AB  - BACKGROUND: Behavioral economics offers a framework to understand choice among
      alternatives. There is no research on the interrelationship between food and
      social activity in overweight and non-overweight children. PURPOSE: The purpose
      of this study is to test the substitutability of food and social interactions
      using behavioral economic methods in overweight and non-overweight youth.
      METHODS: Fifty-four (24 males and 30 females) overweight and non-overweight youth
      aged 9 to 11 years old were tested using a behavioral choice paradigm which
      involved participants responding to earn points exchangeable for food and/or
      social activity. RESULTS: Youth substituted food for social activities when the
      cost of social time with an unfamiliar peer increased (p < 0.05) and substituted
      food for social activities with an unfamiliar peer when the cost of food
      increased (p < 0.05). However, when interacting with a friend was the
      alternative, participants did not substitute food for social interactions.
      CONCLUSIONS: Social interactions can serve as a substitute for food in both lean
      and overweight youth.

PMID- 20052568
TI  - Using ecological momentary assessment to examine antecedents and correlates of
      physical activity bouts in adults age 50+ years: a pilot study.
AB  - BACKGROUND: National recommendations supporting the promotion of multiple short
      (10+ minute) physical activity bouts each day to increase overall physical
      activity levels in middle-aged and older adults underscore the need to identify
      antecedents and correlates of such daily physical activity episodes. PURPOSE:
      This pilot study used Ecological Momentary Assessment to examine the time-lagged
      and concurrent effects of empirically supported social, cognitive, affective, and
      physiological factors on physical activity among adults age 50+ years. METHODS:
      Participants (N = 23) responded to diary prompts on a handheld computer four
      times per day across a 2-week period. Moderate-to-vigorous physical activity
      (MVPA), self-efficacy, positive and negative affect, control, demand, fatigue,
      energy, social interactions, and stressful events were assessed during each
      sequence. RESULTS: Multivariate results showed that greater self-efficacy and
      control predicted greater MVPA at each subsequent assessment throughout the day
      (p < 0.05). Also, having a positive social interaction was concurrently related
      to higher levels of MVPA (p = 0.052). CONCLUSION: Time-varying multidimensional
      individual processes predict within daily physical activity levels.

PMID- 20052569
TI  - Electrophysiological and contractile evidence of the ability of human mesenchymal
      stromal cells to correct vascular malfunction in rats after ionizing irradiation.
AB  - The effect of intravenous administration of human mesenchymal stromal stem cells
      (hMSC) has been evaluated by means of large-conductance calcium-dependent
      potassium channel (BK(Ca)) activity measurements in thoracic aorta smooth muscle
      cells (SMC) obtained from non-fatal whole-body irradiated rats, using the patch
      clamp technique in whole-cell modification, and the standard acetylcholine (ACh)
      test to evaluate functional endothelium integrity using SM contractile
      recordings. Myofilament calcium sensitivity was estimated using simultaneous
      contractile recordings versus [Ca(2+)](i). Arterial blood was measured in intact
      and irradiated rats before and after hMSC administration. Stimulation of isolated
      SMC from the control group of animals with depolarizing voltage steps showed that
      outward K(+) currents sensitive to the BK(Ca) inhibitor paxilline were expressed.
      Outward currents in SMC obtained from irradiated animals were significantly
      reduced on the 30th day of post-irradiation. Irradiation led to a significant
      elevation in arterial blood pressure and reduced ACh-induced relaxation responses
      in irradiated rats as compared with the control group. Simultaneous measurements
      of contractile force and [Ca(2+)](i) showed that myofilament Ca(2+) sensitivity
      had increased following irradiation. Intravenously injected hMSC effectively
      restored BK(Ca) current and the amplitude of ACh-induced endothelium-dependent
      vasodilatation in vascular tissues obtained from post-irradiated rats. SMC
      obtained from irradiated rats treated with hMSC demonstrated a significantly
      increased paxilline-sensitive component of outward potassium currents, indicating
      that BK(Ca) activity had been restored. hMSC administration normalized increased
      blood pressure and myofilament Ca(2+) sensitivity in irradiated animals. When
      administered to healthy rats, hMSC were without effects on either of these. This
      study does not provide any immunohistochemical proof of hMSC engraftment in the
      host rats. PCR analysis showed that hMSCs were negative for hematopoietic cell
      markers and positive for hMSC markers. There were no clinical signs of graft
      versus-host disease throughout the experimental period of 30 days. The data
      obtained suggest that hMSC demonstrate a clearly expressed ability to normalize
      vascular function damaged following irradiation, i.e. to reduce an elevated
      arterial blood pressure and myofilament Ca(2+) sensitivity, and to repair BK(Ca)
      function and endothelium-dependent relaxation in vascular tissues obtained from
      irradiated animals. Thus, hMSC seem to be worthwhile therapeutic approach in
      cases of ionizing irradiation accident or radiation beam therapy.

PMID- 20052570
TI  - Effects of repeated lengthening contractions on skeletal muscle adaptations in
      female rats.
AB  - We examined the adaptation of plantar flexor muscles of female rats to 6 weeks (5
      days/week) of lengthening contractions. After repeated lengthening contractions,
      a decrease in myofiber area of gastrocnemius medialis (26%) was accompanied by an
      increase in extracellular matrix (ECM) (42%) and collagen content (30.9%) without
      changes in muscle mass. Decrease in myofiber area (13%) and muscle mass of soleus
      (19%) was associated with increased collagen content (28%) and ECM (15%).
      Relative number of soleus myofibers stained for fast myosin increased by 26%. For
      plantaris, increases in collagen content (32.3%), percent ECM (17%), and myofiber
      area (6%) were recorded. We also observed (1) increases (3.3%) in the collagen
      content of the Achilles tendon, (2) no change in the crosslink content of any of
      the tissues tested, and (3) no difference in the force-frequency relationship of
      the plantar flexor muscles. Substantial decreases in myofiber areas with
      increases in muscle connective tissue by 6 weeks of repeated lengthening
      contractions did not appear to result in isometric force loss.

PMID- 20052571
TI  - Obstetric risk factors and pelvic floor dysfunction 20 years after first
      delivery.
AB  - INTRODUCTION AND HYPOTHESIS: Intrapartum events at first delivery and subsequent
      childbearing are associated with long-term pelvic floor dysfunction (PFD).
      METHODS: Primigravidae delivered between 1983-1986 were identified; current
      addresses traced through the UK National Health Service database (N = 3002).
      Women completed screening and Sheffield Pelvic Floor Questionnaires (Sheffield
      PAQ). Maternity data were obtained from Standard Maternity Information System.
      Primary outcomes were urinary incontinence (UI), anal incontinence (AI), and
      prolapse (POP). RESULTS: Primary response was 62.1%; 53.8% (n = 985) had >or=1
      PFD symptom and in 71.5% symptoms were bothersome. UI (OR 0.47 95% CI 0.28, 0.81)
      and fecal incontinence (FI; OR 0.32 95% CI 0.13, 0.77) risks were lower after
      first delivery by cesarean section (CS). However, 25% had UI and 12% had FI after
      delivering exclusively by CS. Obesity was a risk factor independent of obstetric
      history. CONCLUSIONS: CS provides incomplete or poorly sustained pelvic floor
      protection by middle age. Obese women were at highest risk and had the most
      severe symptoms.

PMID- 20052572
TI  - An uncommon case of urethrovaginal fistula resulting from tension-free vaginal
      tape.
AB  - Urethrovaginal fistula (UVF) is an uncommon complication after sub-urethral sling
      placement. This is a report of a 51-year-old woman with stress urinary
      incontinence who underwent a tension-free vaginal tape (TVT(R)) in July 2001.
      Thirty-nine months after the procedure, she complained about pelvic and vaginal
      pain, bleeding from the vagina and stress urinary incontinence. The gynecological
      examination revealed a large mid UVF hidden by a 1 cm granuloma. The UVF was
      closed using simple sutures after removal of the sling. No subsequent treatment
      was performed.

PMID- 20052573
TI  - Vaginal weight cone versus assisted pelvic floor muscle training in the treatment
      of female urinary incontinence. A prospective, single-blind, randomized trial.
AB  - INTRODUCTION AND HYPOTHESIS: Vaginal weight cone (VWC) versus assisted pelvic
      floor muscle training (APFMT) in the treatment of urinary incontinence (UI) in
      women. METHODS: One hundred three incontinent women were randomly distributed
      into two groups: group G1 (n = 51) treated with VWC and G2 (n = 52), APFMT. The
      following parameters were performed initially and after treatment: (1) clinical
      questionnaire, (2) visual analogue scale (VAS), (3) 60-min pad test, and (4)
      subjective and objective assessment of pelvic floor muscle (PFM). RESULTS: There
      was a significant decrease in nocturia and urine loss after treatment in both
      groups (p < 0.05). In VAS, there was a significant improvement of all parameters
      in both groups (p < 0.05). The pad test showed significant decrease in both
      groups (p < 0.05). There was a significant increase of PFM strength in both
      groups (p < 0.05). CONCLUSION: There was no difference between groups treated
      with VWC and APFMT.

PMID- 20052574
TI  - Use of pelvic organ prolapse staging systems in published articles of selected
      specialized journals.
AB  - INTRODUCTION AND HYPOTHESIS: A standardized system for reporting pelvic organ
      prolapse is important for clinical communication, patient follow-up, and
      meaningful comparisons between studies. In 1996, the description of the Pelvic
      Organ Prolapse Quantification system (POPQ) was published. We hypothesized that
      its use in published articles of specialized journals would increase over time.
      METHODS: Articles from eight journals in 2004 and 2007 were included if any
      attempt to grade prolapse was mentioned. Reviews, editorials, and abstracts were
      excluded. RESULTS: Use of POPQ increased from 64.9% to 82.1% (p = 0.01) while
      other systems decreased. POPQ was used more frequently in the US than other
      countries. Urologists used POPQ less and Baden-Walker more frequently than other
      specialists. CONCLUSIONS: Use of POPQ has increased in the period studied. This
      trend was observed in all the subgroups analyzed, showing that POPQ is being
      adopted as the universal language of prolapse in the published literature.

PMID- 20052575
TI  - Outcome measures and definition of cure in female stress urinary incontinence
      surgery: a survey of recent publications.
AB  - INTRODUCTION AND HYPOTHESIS: Much variability exists in outcome measures used to
      report success of SUI surgery. We set out to evaluate outcome measures and
      definitions of cure in SUI surgery studies. METHODS: Outcome measures, success
      rates, and definition of cure were analyzed from published series and compared to
      recommendations by leading authorities. RESULTS: Ninety-one publications were
      analyzed. Thirty (33%) utilized solely subjective measures, four (4%) utilized
      only objective measures, and 57 (63%) included both. Sixty-one (67%) used symptom
      questionnaires, 56 (60%) QOL questionnaires, and six (7%) visual analog scale.
      Twelve (13%) used voiding diaries and 52 (56%) used self-reporting as an outcome
      measure. Objective measures: 52 (57%) cough stress test, 37 (41%) urodynamic
      evaluation, 28 (31%) pad testing and a combination in 33 (36%). Few studies
      adhered to one set of outcome recommendations. CONCLUSION: Outcome measures used
      to evaluate success of anti-incontinence procedures lack consensus and
      comparability.

PMID- 20052576
TI  - Polypropylene as a reinforcement in pelvic surgery is not inert: comparative
      analysis of 100 explants.
AB  - INTRODUCTION AND HYPOTHESIS: Currently, most implants used for reinforcement in
      surgical treatment of pelvic floor disorders are knitted monofilament
      polypropylene (PP). While previously recognized as inert, PP is associated with
      high complication rates. Some recent literature suggests polyester prosthetics
      based on poly(ethylene terephthalate) (PET), which may be more inert in vivo.
      METHODS: A sample of 100 implants explanted from patients due to complications
      was examined to evaluate the relative degradation characteristics of PP and PET
      prosthetics. Histological, microscopic (scanning electron microscopy, SEM) and
      chemical analysis (Fourier transform infrared (FTIR) spectroscopy and
      differential scanning calorimetry (DSC)) were conducted on these explants.
      RESULTS: Poly(ethylene terephtahlate) explants appeared to sustain less
      degradation in vivo than the PP explants observed in this cohort. CONCLUSIONS:
      This is the first study to evaluate synthetic implants used in a vaginal approach
      for pelvic floor reinforcement. The study provides evidence contrary to published
      literature characterizing PP as inert in such applications. Additionally, the
      study suggests the need for clinical trials comparatively investigating the
      performance of new types of monofilament prosthetics, such as those comprising
      PET.

PMID- 20052577
TI  - Hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      MS/MS) determination of cocaine and its metabolites benzoylecgonine, ecgonine
      methyl ester, and cocaethylene in hair samples.
AB  - This study reports the development and validation of a method using hydrophilic
      interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) for the
      analysis of cocaine and its metabolites benzoylecgonine (BE), ecgonine methyl
      ester (EME), and cocaethylene (CE) in hair samples. Decontamination was performed
      as follows: Firstly, the aliquot of hair was briefly rinsed with 2 mL
      dichloromethane, then was washed three times with 10 mL 0.01 M phosphate buffer,
      pH 6, for 15 min, followed by 2 mL 2-propanol for less than 2 min, and, finally,
      a last rinse with 2 mL dichloromethane was again done. Cocaine compounds were
      extracted from 10 mg of hair by incubation with 2 mL 0.1 M HCl at 50  degrees C
      for 12 h and purified by solid phase extraction with Oasis MCX cartridges.
      Analysis was performed by LC-MS/MS using an Atlantis HILIC silica chromatographic
      column. The method was fully validated. Linearity was established over the
      concentration range 0.020-10.0 ng/mg for cocaine (COC), 0.010-10.0 ng/mg for BE
      and CE, and 0.005-2.0 ng/mg for EME, and the correlation coefficients were all
      >0.99. Extraction efficiency was >70% for all analytes. Limits of detection were
      0.0005 ng/mg for CE and 0.001 ng/mg for the other analytes (COC, BE, and EME).
      Lower limits of quantification were the lowest points of the calibration curves
      with acceptable accuracy and precision (coefficient of variation <=20%). Intra-
      and inter-day imprecision ranged between 1.5% and 9.5% and 0.7% and 12.6%,
      respectively. Intra- and inter-day inaccuracy ranged from 0.5% to 12.3% and from
      0.7% to 7.1%, respectively. With regard to matrix effects, suppression was <27.5%
      in all cases. The method was applied to the analysis of several samples derived
      from forensic cases.

PMID- 20052578
TI  - Application of surface chemical analysis tools for characterization of
      nanoparticles.
AB  - The important role that surface chemical analysis methods can and should play in
      the characterization of nanoparticles is described. The types of information that
      can be obtained from analysis of nanoparticles using Auger electron spectroscopy
      (AES), X-ray photoelectron spectroscopy (XPS), time-of-flight secondary-ion mass
      spectrometry (TOF-SIMS), low-energy ion scattering (LEIS), and scanning-probe
      microscopy (SPM), including scanning tunneling microscopy (STM) and atomic force
      microscopy (AFM), are briefly summarized. Examples describing the
      characterization of engineered nanoparticles are provided. Specific analysis
      considerations and issues associated with using surface-analysis methods for the
      characterization of nanoparticles are discussed and summarized, with the impact
      that shape instability, environmentally induced changes, deliberate and
      accidental coating, etc., have on nanoparticle properties.

PMID- 20052579
TI  - Coupled stochastic resonance to improve chromatography determinations.
AB  - Traditional bistable stochastic resonance has been demonstrated as an effective
      tool to detect the weak signal in a strong noise background. To achieve a better
      signal-to-noise ratio for the output signal, a coupled stochastic resonance was
      developed by nonlinearly coupling two double-well potential systems. The response
      characteristics of coupled stochastic resonance subjected to analytical signals
      have been investigated and compared with those of bistable stochastic resonance.
      The improvement of chromatographic determination with the proposed coupled
      stochastic resonance was validated by both simulated signals and chromatographic
      signals. The weak signals from both simulated data and plasma samples with
      different concentrations were all amplified significantly and the quantitative
      relationship between different concentrations and responses was kept well. It is
      reasonable to believe that coupled stochastic resonance could play an important
      role in applications where quantitative determination of low-concentration
      samples is crucial.

PMID- 20052580
TI  - Evaluation of microwave-assisted enzymatic digestion and tandem mass spectrometry
      for the identification of protein residues from an inorganic solid matrix:
      implications in archaeological research.
AB  - A method based on microwave-assisted enzymatic digestion and liquid
      chromatography-tandem mass spectrometry analysis is presented for the
      identification of proteins incorporated within solid matrices using protein
      standards bound to experimental cooking pottery as a validation model. The
      implementation of microwave irradiation allowed for a significant decrease in
      overall analysis time in addition to select enhancement of peptide recovery as
      determined by label-free relative quantitation. We envision that the reported
      methodology will provide new avenues for scientific discovery in areas such as
      archaeology and forensics. Results of this series of experiments are part of an
      ongoing project directed at developing a comprehensive methodology for extracting
      proteinaceous residues from archaeological pottery.

PMID- 20052581
TI  - Chemical and structural characterization of carbon nanotube surfaces.
AB  - To utilize carbon nanotubes (CNTs) in various commercial and scientific
      applications, the graphene sheets that comprise CNT surfaces are often modified
      to tailor properties, such as dispersion. In this article, we provide a critical
      review of the techniques used to explore the chemical and structural
      characteristics of CNTs modified by covalent surface modification strategies that
      involve the direct incorporation of specific elements and inorganic or organic
      functional groups into the graphene sidewalls. Using examples from the
      literature, we discuss not only the popular techniques such as TEM, XPS, IR, and
      Raman spectroscopy but also more specialized techniques such as chemical
      derivatization, Boehm titrations, EELS, NEXAFS, TPD, and TGA. The chemical or
      structural information provided by each technique discussed, as well as their
      strengths and limitations. Particular emphasis is placed on XPS and the
      application of chemical derivatization in conjunction with XPS to quantify
      functional groups on CNT surfaces in situations where spectral deconvolution of
      XPS lineshapes is ambiguous.

PMID- 20052583
TI  - Variability in symbiotic effectiveness of native Rhizobia in acid stress.
AB  - In vitro experiments had been conducted to assess the effect of pH on different
      native isolates of Rhizobium from the lower Brahmaputra valley region of Assam,
      India. The growth rate of all the Rhizobium isolates were compared growing at
      three different pH levels viz. 4.5, 5.5 and 6.5. All the slow-growing Rhizobium
      isolates (AR1, BR5, BR8, BR12, GR13, AR10, BR13, GM16, GR21) were showed better
      growth at all the pH levels, whereas three fast-growing Rhizobium isolates (PR7,
      PR12 and PR16) failed to grow at pH 4.5 and 5.5 and could show growth only at pH
      6.5. Experiments were also conducted in vitro to determine the symbiotic
      effectiveness of all the Rhizobium isolates with test legume, green gram
      (Phaseolus aureus Roxb.) at three different pH levels for 42 days and significant
      differences were observed on nodulation, nodule dry weight and nitrogenase
      activity. The acid-tolerant isolates could be used as bioinoculant for
      enhancement of growth of leguminous plants in the acid soils.

PMID- 20052582
TI  - The role of the disulfide bond in the interaction of islet amyloid polypeptide
      with membranes.
AB  - Human islet amyloid polypeptide (hIAPP) forms amyloid fibrils in pancreatic
      islets of patients with type 2 diabetes mellitus. It has been suggested that the
      N-terminal part, which contains a conserved intramolecular disulfide bond between
      residues 2 and 7, interacts with membranes, ultimately leading to membrane damage
      and beta-cell death. Here, we used variants of the hIAPP(1-19) fragment and model
      membranes of phosphatidylcholine and phosphatidylserine (7:3, molar ratio) to
      examine the role of this disulfide in membrane interactions. We found that the
      disulfide bond has a minor effect on membrane insertion properties and peptide
      conformational behavior, as studied by monolayer techniques, (2)H NMR, ThT
      fluorescence, membrane leakage, and CD spectroscopy. The results suggest that the
      disulfide bond does not play a significant role in hIAPP-membrane interactions.
      Hence, the fact that this bond is conserved is most likely related exclusively to
      the biological activity of IAPP as a hormone.

PMID- 20052584
TI  - Fusarium verticillioides (Saccardo) Nirenberg associated with hardlock of cotton.
AB  - Boll rots of cotton (Gossypium hirsutum L.) are common in the humid areas of the
      Southeastern US. One type of boll damage that may be differentiated from others
      is hardlock, with symptoms that include compression of the fibers within
      individual locules of mature, open cotton bolls without further obvious
      disintegration of the lint or damage to the carpel wall. The principal economic
      effect is that the boll's lint is unharvestable by mechanical cotton pickers.
      This disease is endemic to the Southeast and can cause severe yield losses up to
      70% in some fields. Scanning electron microscopy images of fibers from hardlocked
      bolls showed flattened and twisted tissue compared to fibers from healthy bolls.
      Fusarium verticillioides (Saccardo) Nirenberg was the fungus most commonly
      isolated from seeds of developing cotton bolls. Flowers inoculated with F.
      verticillioides on the day of bloom by spraying a spore suspension onto the
      flowers developed significantly (P < 0.05) more hardlock symptoms compared to
      untreated controls. The infection process was analyzed using a F. verticillioides
      isolate tagged with green fluorescent protein (GFP). When it was applied to
      cotton flowers on the day of bloom, the GFP-tagged F. verticillioides strain was
      detected in the stigma and style by 2 days after bloom (DAB) and in developing
      seeds at 4, 6, 8, 10, 16, 20, 40, and 60 (open bolls) DAB. By 8 DAB, the GFP F.
      verticillioides was isolated from over 80% of developing seeds.

PMID- 20052585
TI  - Structural and catalytic properties of the D-3-hydroxybutyrate dehydrogenase from
      Pseudomonas aeruginosa.
AB  - To put forward BDH from Pseudomonas aeruginosa's enzymatic properties, we report
      a two-step purification of BDH and its gene sequencing allowing the investigation
      of its structural properties. Purification of BDH was achieved, using ammonium
      sulfate fractionation and Blue Sepharose CL-6B affinity chromatography. SDS-PAGE
      analysis reveals a MM of 29 kDa, whereas the native enzyme showed a MM of 120 kDa
      suggesting a homotetrameric structure. BDH encoding gene sequence shows a
      nucleotide open reading frame sequence of 771 bp encoding a 265 amino acid
      residues polypeptide chain. The modeling analysis of the three dimensional
      structure fits with the importance of amino acids in the catalysis reaction
      especially a strictly conserved tetrad. Amino-acid residues in interaction with
      the coenzyme NAD(+) were also identified.

PMID- 20052586
TI  - Complications of laser prostatectomy: a review of recent data.
AB  - INTRODUCTION: Laser techniques for the treatment of bladder outlet obstruction
      (BOO) due to benign prostate enlargement (BPE) have emerged as an alternative to
      transurethral resection of the prostate (TURP) and open prostatectomy (OP).
      MATERIALS AND METHODS: A Medline search over the past 4 years was performed to
      assess the safety, intra- and postoperative morbidity of various laser
      techniques. RESULTS: Data on holmium laser enucleation of the prostate (HoLEP)
      show the highest grade of evidence with two meta-analyses available and prove the
      low intra- and postoperative morbidity with reproducible long-term results.
      Photoselective vaporization of the prostate (PVP) with the Greenlightlaser
      (potassium titanyl phosphate, KTP or lithium borate, LBO) is characterized by
      excellent haemostatic properties in patients with or without oral
      anticoagulation. Long-term results show a reoperation rate comparable with TURP;
      however, there is a lack of randomized trials. Various types of diode lasers with
      different wavelengths are available for laser vaporization; despite their
      favourable haemostatic properties, a higher invasion depth seems to result in
      necrosis of the tissue leading to a higher rate of reoperation. Thulium-laser
      resection of the prostate shows promising intra- and postoperative morbidity, but
      data are limited and initial results need to be confirmed in large-scale trials.
      CONCLUSION: In summary, HoLEP- and KTP-, or LBO-laser vaporization of the
      prostate are the most mature techniques of laser prostatectomy and treatment
      alternatives to TURP and OP, whereas the clinical value and durability of
      procedures with diode laser systems and the thulium laser need to be confirmed in
      high-quality prospective RCTs.

PMID- 20052587
TI  - Ribosomal therapy in the treatment of recurrent acute adenoiditis.
AB  - The aim of this study was to evaluate the efficacy of an oral ribosomal
      immunotherapy in the management of children with recurrent acute adenoiditis
      (RAA). 60 children with RAA were included and randomly assigned into two groups
      (group A and B). Group A children underwent ribosomal prophylaxis, while group B
      received a placebo. Before, at the end and 6 months after start of the therapy,
      children underwent medical history, ENT examination, plasma levels of
      immunoglobulins class E, A, G, M (IgE, IgA, IgG, IgM), tympanometry, active
      anterior rhinomanometry and VAS scores by children' parents. After the treatment
      and at the end of the study, in the group A, the serum concentration of IgE was
      significantly (P < 0.05) lower than in group B (77.34 +/- 6.23 vs. 95.49 +/- 7.07
      mg/dl; 74.82 +/- 6.26 vs. 94.44 +/- 7.44 mg/dl), IgA titers were significantly (P
      < 0.05) higher than in group B (312.04 +/- 18.41 vs. 213.20 +/- 11.82; 309.07 +/-
      18.33 vs. 211.73 +/- 11.54 mg/dl) as well as serum concentration of IgG (1401.12
      +/- 118.81 vs. 1101.81 +/- 109.64 mg/dl; 1412.19 +/- 116.43 vs. 1144.06 +/-
      103.58 mg/dl). At the end of the study, comparison between the two groups showed,
      in group A: 77% of children (n = 23), versus 23% (n = 7) of group B, with a type
      A tympanogram; significant (P < 0.05) nasal flow decrease at the rhinomanometric
      measures; VAS scores were significantly (P < 0.05) improved (1.8 +/- 0.22 vs. 5.1
      +/- 0.59) and frequency, severity and social impact of RAA episodes were
      significantly (P < 0.05) lower than group B. Our results show the therapeutic
      effectiveness of this approach in the prophylaxis of recurrent acute adenoiditis.

PMID- 20052588
TI  - Response evaluation in head and neck oncology.

PMID- 20052589
TI  - Assay-based response evaluation in head and neck oncology: requirements for
      better decision making.
AB  - This article gives an overview on different current strategies of assay-based
      response evaluation in head and neck squamous cell carcinomas (HNSCC) and
      critically summarizes their role and needs for future clinical evaluation. Due to
      a growing amount of data of phase III clinical trials of multimodality treatment
      options for HNSCC, treatment planning in regard to optimal outcome is becoming an
      interdisciplinary challenge. New concepts such as induction chemotherapy with bi-
      or ternary combinations of chemotherapeutics, integration of targeted therapies,
      concurrent and sequential chemoradiation concepts, and multimodality-based organ
      preservation strategies strongly compete with traditional definitive surgical
      procedures. Moreover, the outcome is difficult to predict due to heterogeneity of
      a tumor's response, impaired late functional outcome, and increased late toxicity
      if simultaneously applied to radiation. Retrospectively looking at non-responders
      with tumors classified as resectable, primary surgery is very likely to have
      achieved better results, since chemoradiation causes a high degree of early and
      late toxicities leading to extremely complicated terms and conditions in surgery
      following current multimodal therapeutic strategies. Unfortunately, predictive
      information on response characteristics of a given tumor before starting the
      therapy is not available in daily routine, although heterogeneity in response of
      a given tumor entity to treatments has been known for decades. Therefore, current
      therapy strategies for HNSCC still have to ignore this fact, creating an urgent
      need for the development of proper predictive assays. There are interesting
      clinical observations showing that response on induction chemotherapy may predict
      the outcome after radiotherapy. Some trials use this empiric phenomenon to pre
      select non-responders for primary surgical treatment avoiding severe salvage
      complications after failure of complete chemoradiation treatment. Moving one step
      further, recent literature and our own investigations implicate that response
      evaluation of the individual patient's HNSCC in a suitable ex vivo assay just
      before starting the treatment is mature for clinical research. To this end,
      essential needs and hints are addressed and discussed.

PMID- 20052590
TI  - Laryngeal carcinoma lymph node metastasis and disease-free survival correlate
      with MASPIN nuclear expression but not with EGFR expression: a series of 108
      cases.
AB  - Despite advances in laryngeal squamous cell carcinoma (LSCC) treatment, patient
      survival has not improved in the last two decades. Novel, more effective
      strategies should be based on receptor-mediated LSCC-targeted therapy. The
      epidermal growth factor receptor (EGFR) is the most widely studied molecular
      target. MASPIN multifaceted anti-tumor effects have been rarely evaluated in
      LSCC. The aims of this study were to investigate EGFR and MASPIN expression and
      the role of sub-cellular MASPIN localization in LSSC. MASPIN and EGFR expression
      and the sub-cellular localization of MASPIN were assessed using a computerized
      image analysis system in 108 consecutive cases of operable LSCC. The rates of
      occurrence of lymph node metastases and recurrent disease were lower in patients
      with a nuclear pattern of MASPIN expression (p = 0.004, p = 0.0028). As expected,
      the loco-regional recurrence rate was lower in N0 patients (p = 0.009), but the
      disease recurrence rate was even lower in N0 patients with a nuclear localization
      of MASPIN (p = 0.020). Disease-free survival was longer in cases of LSCC with a
      nuclear MASPIN pattern (p = 0.003). The intensity of EGFR reactivity and the EGFR
      area fraction were unrelated to the clinico-pathological and prognostic
      parameters in LSCC. A nuclear MASPIN pattern is a promising prognostic indicator
      in LSCC, but further evidence is needed before elective neck dissection can be
      considered for cN0 LSCCs with a non-nuclear MASPIN pattern. Although a better
      understanding of the mechanisms behind sub-cellular MASPIN localization is
      mandatory, re-activating nuclear MASPIN in association with specific
      chemotherapeutic agents may be an important goal in the treatment of LSCC.

PMID- 20052591
TI  - Postmortem redistribution of THC in the pig.
AB  - To improve the knowledge of the postmortem redistribution of Delta(9)
      tetrahydrocannabinol (THC), an animal model using the Large White pig has been
      developed, whereby 15 pigs received an intravenous injection of THC (200 ug/kg
      body weight) and were euthanized 2 h after administration. An autopsy was
      performed on three pigs immediately after being euthanized while the others were
      stored in supine position at ambient temperature for 6, 15, 24, or 48 h. THC
      concentration in blood from the vena cava decreased after death whereas left or
      right cardiac blood concentrations increased. No blood specimens collected from
      different sites of the carcasses adequately reflected the perimortem THC
      concentrations. The highest concentrations of THC at anytime were observed in
      lung tissue, and brain tissue seemed to present the most stable concentrations
      over time. This study can assist toxicologists in determining which specimens
      can, most appropriately, be used for interpretation of cannabinoid concentrations
      in postmortem specimens.

PMID- 20052593
TI  - Low vagal tone is associated with impaired post stress recovery of
      cardiovascular, endocrine, and immune markers.
AB  - Reduced heart rate variability (HRV) and delayed blood pressure recovery are
      associated with increased cardiovascular risk. Besides this evident link, the
      vagus is thought to play an inhibitory role in the regulation of other allostatic
      systems, including inflammation and the hypothalamic-pituitary-adrenal (HPA)
      axis. However, human evidence is scarce. To further explore these associations
      and with special regard to the postulated mediating role of the vagus, we
      hypothesised that subjects with low vagal tone as indexed by reduced resting HRV
      would show impaired post-stress recovery of cardiovascular, endocrine and immune
      system markers involved in cardiovascular pathology. 44 healthy men underwent a
      standardised mental stress test. Besides continuous measurement of systolic and
      diastolic blood pressure (SBP, DBP), heart rate (HR), and HRV serum cortisol,
      tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured
      before, after, 20, and 60 min after stress. Low versus high HRV groups was
      defined by median split on resting HRV (RMSSD). The task elicited significant
      time effects for SBP, DBP, HR, HRV, cortisol, and TNF-alpha. Subjects with low
      baseline HRV showed almost no modulation of HRV coupled with overall reduced HRV
      levels, and impaired recovery of DBP, cortisol, and TNF-alpha. Confirming our
      hypothesis, low vagal tone was associated with impaired recovery of
      cardiovascular, endocrine, and immune markers in healthy males. The data support
      an inhibitory role of the vagus in the regulation of allostatic systems as
      described in the neurovisceral integration model. We posit reduced resting HRV as
      a risk marker for future cardiovascular and other stress-related disease.

PMID- 20052592
TI  - A definition of normovolaemia and consequences for cardiovascular control during
      orthostatic and environmental stress.
AB  - The Frank-Starling mechanism describes the relationship between stroke volume and
      preload to the heart, or the volume of blood that is available to the heart--the
      central blood volume. Understanding the role of the central blood volume for
      cardiovascular control has been complicated by the fact that a given central
      blood volume may be associated with markedly different central vascular
      pressures. The central blood volume varies with posture and, consequently, stroke
      volume and cardiac output (Q) are affected, but with the increased central blood
      volume during head-down tilt, stroke volume and Q do not increase further
      indicating that in the supine resting position the heart operates on the plateau
      of the Frank-Starling curve which, therefore, may be taken as a functional
      definition of normovolaemia. Since the capacity of the vascular system surpasses
      the blood volume, orthostatic and environmental stress including bed
      rest/microgravity, exercise and training, thermal loading, illness, and
      trauma/haemorrhage is likely to restrict venous return and Q. Consequently the
      cardiovascular responses are determined primarily by their effect on the central
      blood volume. Thus during environmental stress, flow redistribution becomes
      dependent on sympathetic activation affecting not only skin and splanchnic blood
      flow, but also flow to skeletal muscles and the brain. This review addresses the
      hypothesis that deviations from normovolaemia significantly influence these
      cardiovascular responses.

PMID- 20052594
TI  - Topoisomerase IIalpha expression rather than gene amplification predicts
      responsiveness of adjuvant anthracycline-based chemotherapy in women with primary
      breast cancer.
AB  - INTRODUCTION: Adjuvant anthracycline-based chemotherapy (AbCTX) is a standard
      treatment for patients with primary breast cancer. Its main target is
      topoisomerase IIalpha (TopIIa), a nuclear protein which is important for DNA
      replication and mitosis. We propose that the overexpression of the TopIIa protein
      or amplification of the TopIIa gene may be useful in predicting increased
      responsiveness towards AbCTX. METHODS: Tumor tissues of 118 patients who received
      adjuvant AbCTX were examined by immunohistochemistry (IHC) and fluorescence in
      situ hybridisation (FISH) for TopIIa and HER2. For IHC, the primary antibodies
      485 (Dako) and NCL-TOPOIIA (Novocastra) were used. FISH analysis was performed
      with the SPEC HER2/CEP 17 Dual Color Probe (Zytovision) and LSI TOP 2A Spectrum
      Orange/CEP 17 Spectrum Green probe (Abbott). TopIIa IHC was evaluated by the
      immunoreactive score (IRS). FISH amplification was stated at an HER2-TopIIa/CEP
      17 ratio > or = 2, deletion of TopIIa at a ratio <0.8. RESULTS: The median age of
      the patient population was 50 years (range 23-77), 76 (64%) had tumors >2 cm in
      size, 98 (85%) were nodal positive, and 72 (66%) estrogen-receptor positive.
      Chemotherapy regimes consisted of epirubicin-cyclophosphamide (EC 40 pts), EC-CMF
      (18 pts), FAC/FEC (33 pts), anthracycline-taxane combinations (23 pts) and others
      (4 pts). After IHC, it was found that 19% of the tumors were positive for HER2
      (3+) and the median IRS for TopIIa staining was 2 (49% positive); 28 (24%) tumors
      showed HER2 amplification, therefrom 20/22 (91%) within the HER2 3+ group. TopIIa
      gene was amplified in 17 cases (16%) and deletion was seen in 6 (5%) tumors. Of
      all cases with HER2 gene amplification, 14 (50%) cases of TopIIa co-amplification
      and one case of deletion were seen. Looking at histological parameters, TopIIa
      IHC correlated with nodal status (P = 0.018) and high grading (G3) (P = 0.047).
      After a median follow-up of 42 months (range 1-242), a significant prognostic
      factor for local recurrence was HER2 positivity (IHC P = 0.013 and FISH P =
      0.023). Thirty-two patients developed metastasis (27%), which was correlated with
      HER2 FISH positivity (P = 0.024) and, as a trend, Top IIa IHC negativity (P =
      0.094); 25 (21%) patients died from the disease. Negative prognostic parameters
      were the lack of estrogen-receptor expression (P = 0.008), lymphangiosis (P =
      0.02), and TopIIa IHC negativity (P = 0.03). CONCLUSION: In this cohort of
      patients, HER2 positivity indicated higher rates of local and distant recurrence.
      In contrast, TopIIa IHC positivity predicted lower risk of metastases and death,
      thus being a positive-predictive factor for the responsiveness to AbCTX. TopIIa
      gene amplification did not add predictive information. Therefore, we conclude
      that TopIIa protein expression might rather be the target of anthracyclines
      independent from gene copy number.

PMID- 20052595
TI  - Constitutive activation of signal transducer and activator of transcription 3
      regulates expression of vascular endothelial growth factor in human meningioma
      differentiation.
AB  - PURPOSE: Janus tyrosine kinases (JAKs) and signal transducer and activator of
      transcription factors (STATs), especially STAT3, are constitutively activated in
      human cancers. The function of STAT3 in the pathogenesis of meningioma remains
      unknown. In this study, we investigated the role of JAK1/STAT3 regulating
      vascular endothelial growth factor (VEGF) expression in the occurrence and
      progression of human meningioma. METHODS: We detected the expression of JAK1, p
      JAK1, STAT3, p-STAT3, and VEGF in human meningioma and normal dura tissues by RT
      PCR, Western blot analysis, and immunohistochemistry. RESULTS: JAK1, p-JAK1,
      STAT3, p-STAT3, and VEGF showed high expression in grade I and grade II
      meningioma. The level of STAT3 activation was associated with VEGF expression;
      all meningioma tumors that expressed p-STAT3 also expressed VEGF. Both frequency
      of positivity and expression were enhanced with increasing tumor grade; high
      frequencies and levels were found in grade II tumors, with no expression detected
      in normal dura tissues (P < 0.05). CONCLUSIONS: VEGF is directly regulated by
      constitutive STAT3 activity and associated with meningioma differentiation. STAT3
      has an important role in the occurrence and development of human meningioma by
      regulating VEGF expression.

PMID- 20052597
TI  - Quantifying the thermal heat requirement of Brassica in assessing biophysical
      parameters under semi-arid microenvironments.
AB  - Evaluation of the thermal heat requirement of Brassica spp. across agro
      ecological regions is required in order to understand the further effects of
      climate change. Spatio-temporal changes in hydrothermal regimes are likely to
      affect the physiological growth pattern of the crop, which in turn will affect
      economic yields and crop quality. Such information is helpful in developing crop
      simulation models to describe the differential thermal regimes that prevail at
      different phenophases of the crop. Thus, the current lack of quantitative
      information on the thermal heat requirement of Brassica crops under debranched
      microenvironments prompted the present study, which set out to examine the
      response of biophysical parameters [leaf area index (LAI), dry biomass
      production, seed yield and oil content] to modified microenvironments. Following
      2 years of field experiments on Typic Ustocrepts soils under semi-arid climatic
      conditions, it was concluded that the Brassica crop is significantly responsive
      to microenvironment modification. A highly significant and curvilinear
      relationship was observed between LAI and dry biomass production with accumulated
      heat units, with thermal accumulation explaining >or=80% of the variation in LAI
      and dry biomass production. It was further observed that the economic seed yield
      and oil content, which are a function of the prevailing weather conditions, were
      significantly responsive to the heat units accumulated from sowing to 50%
      physiological maturity. Linear regression analysis showed that growing degree
      days (GDD) could indicate 60-70% variation in seed yield and oil content,
      probably because of the significant response to differential thermal
      microenvironments. The present study illustrates the statistically strong and
      significant response of biophysical parameters of Brassica spp. to
      microenvironment modification in semi-arid regions of northern India.

PMID- 20052598
TI  - Surveillance of HIV drug resistance transmission in Iran: experience gained from
      a pilot study.
AB  - We performed a pilot surveillance study on transmitted HIV drug resistance (TDR)
      in Iran, with specimens collected and stored as dried blood spots (DBS). The
      protease region and relevant positions in the reverse transcriptase region of the
      pol gene were sequenced to detect mutations known to be associated with
      resistance to drugs in standard first-line regimens. Seventy-three specimens were
      collected, with 39 (53%) specimens yielding sequence from both protease and at
      least part of RT. Specimens were almost exclusively HIV-1 subtype CRF 35_A1D
      based on pol sequencing. Mutations were restricted to RT, with D67DG and V75AV
      each seen in a single specimen. An atypical protease inhibitor mutation, I47M,
      appeared at a resistance-associated position in protease from a single specimen.
      These preliminary data showed that the rate of transmitted drug resistance in
      Iran, within the areas sampled, was 5.1% (2/39). However, the small sample size
      makes this figure only an approximation. Due to the sampling strategy and
      resulting small sample size, we were unable to accurately calculate TDR rates for
      individual areas using the WHO HIV drug resistance threshold survey method.
      Increasing the sample size and improving the yield from DBS would improve the
      accuracy of drug resistance surveillance and facilitate wider application of this
      methodology in Iran.

PMID- 20052599
TI  - GP4 of porcine reproductive and respiratory syndrome virus contains a
      neutralizing epitope that is susceptible to immunoselection in vitro.
AB  - Glycoprotein 4 (GP4) of porcine reproductive and respiratory syndrome virus
      (PRRSV) contains a highly variable neutralizing epitope. The present study aimed
      to investigate whether this epitope is susceptible to immunoselection by
      antibodies in vitro. Cultivation of PRRSV in vitro in the continuous presence of
      neutralizing monoclonal antibodies (mAbs) directed against this epitope resulted
      in the selection of mAb-resistant PRRSV strains within five passages. Comparison
      of the GP4 amino acid (aa) sequence of the original PRRSV strain with the GP4 aa
      sequences of the mAb-resistant PRRSV strains revealed aa substitutions within
      this epitope. In conclusion, this study shows that the neutralizing epitope on
      GP4 is susceptible to immunoselection by antibodies in vitro.

PMID- 20052600
TI  - Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism
      of transforming growth factor-beta1 gene on the prevalence of vertebral fractures
      in postmenopausal osteoporosis.
AB  - A T869-->C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene
      is reported to be associated with genetic susceptibility to both osteoporosis and
      vertebral fractures. A low serum 25-hydroxyvitamin D [25(OH)D] level is known to
      be associated with a higher risk for hip fracture. This study aimed to assess a
      possible cooperative effect of the gene polymorphism and vitamin D status on
      vertebral fracture risk. The prevalence of vertebral fracture in 168
      postmenopausal female patients with osteoporosis was analyzed, and its
      association with the TGF-beta1 gene polymorphism and serum 25(OH)D concentration
      was assessed cross-sectionally. The fracture prevalence increased according to
      the rank order of the TGF-beta1 genotypes CC < CT < TT, as expected. A
      significant difference was found not only between the CC and TT genotypes (P =
      0.005) but also between the CC and CT genotypes (P < 0.05) when the patients with
      serum 25(OH)D of more than the median value [22 ng/ml (55 nmol/l)] were analyzed.
      On the other hand, when those with serum 25(OH)D of less than the median value
      were analyzed, the protective effect of the C allele against the fracture was
      blunted; statistical significance in the difference of the fracture prevalence
      was lost between the CC genotype and the other genotypes. These data suggest that
      vitamin D fulfillment is prerequisite for the TGF-beta1 genotype in exerting its
      full effect on the fracture prevalence.

PMID- 20052601
TI  - Binding characteristics of the osteoarthritis-associated protein asporin.
AB  - Asporin is an extracellular matrix (ECM) protein that regulates cartilage matrix
      gene expression and cartilage formation by modulating the transforming growth
      factor-beta (TGF-beta) signaling pathway. Our previous studies have indicated
      that asporin binds to TGF-beta1 directly and inhibits TGF-beta1-mediated
      expression of cartilage matrix genes. However, it is still unknown how asporin
      interacts with TGF-beta1 and influences its activity. Using competition assays,
      we determined that amino acids 159-205 of asporin mediate its interaction with
      TGF-beta1 and effectively repress TGF-beta1-induced cartilage matrix gene
      expression. Asporin also has a binding ability to type II collagen in vitro, but
      its binding pattern is different from that of TGF-beta1. In contrast with
      previous in vivo findings, asporin did not affect the interaction between TGF
      beta1 and the TGF-beta type II receptor (TbetaRII) by itself or in the presence
      of type II collagen in vitro. However, in the presence of heparin/heparan
      sulfate, asporin inhibits the interaction between TGF-beta and TbetaRII in vitro.
      These findings suggest that asporin is one of the important cartilage matrix
      proteins that binds to the ECM and TGF-beta1 and thereby modulates interactions
      between TGF-beta and its signaling receptors.

PMID- 20052602
TI  - First fractures among postmenopausal women with osteoporosis.
AB  - After the occurrence of the first fracture, osteoporosis is no longer a "silent"
      disease, and the patient's risk for future fracture is increased several fold. We
      assessed the location of first osteoporotic fractures among women with
      osteoporosis. The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a
      fracture outcomes study of postmenopausal women with osteoporosis. All subjects
      received supplements containing 500 mg elemental calcium and 400-600 IU vitamin
      D. We assessed the location of first fractures among women with osteoporosis and
      no previous fractures at baseline from the placebo group of this trial after 3
      years of follow-up. Prespecified fracture sites included vertebral fractures and
      nonvertebral fractures as defined in the MORE study protocol. Among 875 women
      (mean age, 64.5 +/- 7.4 years) with no prevalent vertebral or nonvertebral
      fractures, 9% experienced their first fracture event during the trial. Fractures
      of radius and spine each occurred in 3% of patients. Fractures at other
      individual sites included ankle (0.6%), metatarsal (0.6%), humerus (0.5%), rib
      (0.5%), patella (0.3%), leg (0.2%), hip (0.2%), and clavicle (0.1%). These data
      suggest that for postmenopausal women with osteoporosis but no previous
      fractures, skeletal care should include a focus on preventing spine and radius
      fractures.

PMID- 20052603
TI  - Transgenic expression of walleye dermal sarcoma virus rv-cyclin gene in zebrafish
      and its suppressive effect on liver tumor development after carcinogen treatment.
AB  - A retrovirus homologue gene of cellular cyclin D1, walleye dermal sarcoma virus
      rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish
      under the control of liver fatty acid-binding protein (lfabp) promoter. To
      prevent possible fatality caused by overexpression of the oncogene, the
      GAL4/upstream activation sequence (GAL4/UAS) system was used to maintain the
      transgenic lines. Thus, both GAL4-activator [Tg(lfabp:GAL4)] and UAS-effector
      [Tg(UAS:rvcyclin)] lines were generated, and the rv-cyclin gene was activated in
      the liver after crossing these two lines. Since no obvious neoplasia phenotypes
      were observed in the double-transgenic line, cancer susceptibility of the
      transgenic fish expressing rv-cyclin was tested by carcinogen treatment.
      Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) were more
      resistant to the carcinogen than siblings not expressing this gene (rvcyclin-).
      Lower incidences of multiple and malignant liver tumors were observed in
      rvcyclin+ than in rvcyclin- fish, and the liver tumors in the rvcyclin+ group
      appeared later and were less malignant. These results suggest that expression of
      rv-cyclin protects the fish liver from carcinogen damage and delays onset of
      malignancy. These findings indicate that transgenic fish models are powerful
      systems for investigating mechanisms of inhibition and regression of liver
      tumors.

PMID- 20052604
TI  - Coprophagy-related interspecific nocturnal interactions between Japanese macaques
      (Macaca fuscata yakui) and sika deer (Cervus nippon yakushimae).
AB  - The influence of sympatric large animals on the sleeping behavior of primates in
      the wild is still largely unknown. In this study, we observed behaviors of wild
      Japanese macaques (Macaca fuscata yakui) at their sleeping sites, using a highly
      sensitive video camera. We found evidence of nocturnal interspecific
      interactions, such as agonistic interactions, between Japanese macaques and sika
      deer (Cervus nippon yakushimae). Deer approached sleeping clusters of macaques,
      which slept on the ground, to eat their feces or unidentified materials near the
      sleeping clusters, and as a result, the macaques were often quickly displaced
      from their sleeping site. There was a significant difference in the occurrence of
      macaque-deer agonistic interactions between seasons. Our results suggested that
      the size of the sleeping cluster, the number of adult macaques in the cluster,
      and the existence of adult males in the cluster did not influence the occurrence
      of the agonistic interactions. Finally, we discuss the influence of this
      interaction on macaques and speculate on the influential factors leading to
      nocturnal coprophagy of macaques' feces by deer.

PMID- 20052605
TI  - Nonaggressive interventions by third parties in conflicts among captive Bornean
      orangutans (Pongo pygmaeus).
AB  - Whereas orangutans are regarded as semisolitary animals in the wild, several
      studies have reported frequent social interactions, including aggression, among
      orangutans in captivity. As yet, there is a lack of knowledge about how they cope
      with aggression. In this report, we provide a number of new observations of
      interventions by third parties in aggressive interactions within a captive group
      of Bornean orangutans (Pongo pygmaeus) in the Tama Zoological Park, Japan. We
      observed that an adult female and a juvenile male orangutan intervened in
      aggressive interactions. The victim was a newly introduced juvenile female who
      was unrelated to anyone in the zoo. The ways in which the orangutans intervened
      were not aggressive, as the interveners simply aimed to separate the opponents,
      and these interventions did not lead to further aggression in almost every case.
      Our observations suggest that third parties can play an important role in
      managing aggressive conflicts among captive orangutans and, under conditions in
      which orangutans share limited space, nonaggressive interventions by third
      parties for settling conflicts appear. It is possible that orangutans may
      actively promote the peaceful coexistence of other individuals.

PMID- 20052606
TI  - Never smile at a crocodile: betting on electronic gaming machines is intensified
      by reptile-induced arousal.
AB  - Tourists at the Koorana Saltwater Crocodile Farm in Coowonga, Queensland,
      Australia, including 62 males and 41 females, aged 18-66 (M = 34.2, SD = 13.3),
      were randomly assigned to play a laptop-simulated Electronic Gaming Machine (EGM)
      either: (1) prior to entry, or (2) after having held a 1-m saltwater-crocodile.
      Gambling behavior; including bet-size, speed of betting, final payouts and trials
      played on the EGM; was investigated with respect to participants' assigned
      arousal condition, problem-gambling status, and affective state. At-risk gamblers
      with few self-reported negative emotions placed higher average bets at the EGM
      after having held the crocodile when compared to the control. In contrast, at
      risk gamblers with many self-reported negative emotions placed lower average bets
      at the EGM after having held the crocodile. The results suggest that high arousal
      can intensify gambling in at-risk players, but only if this feeling state is not
      perceived as a negative emotion.

PMID- 20052607
TI  - Personality, gender, and family history in the prediction of college gambling.
AB  - The present study examined the degree to which gambling behaviors and gambling
      relevant cognitive distortions could be predicted by personality factors, gender,
      and familial history of substance use and gambling problems in a large sample of
      college students (N = 581). Results indicate that parental gambling problems and,
      especially for males, a propensity to experience negative emotions predicted time
      spent gambling and gambling problems. Negative emotionality, along with parental
      substance use problems, impulsivity, and being male predicted gambling-related
      cognitive distortions. The differing pattern for impulsivity with respect to
      behaviors and beliefs might be explained by the low accessibility of gambling
      venues for the student population. We compare the present findings with past
      studies examining gambling behaviors in adult populations.

PMID- 20052608
TI  - Evaluation of the efficacy of a dental plaque control program in autistic
      patients.
AB  - The aim of this study was to verify the efficacy of a programme for dental plaque
      control in autistics. Patients were evaluated on five occasions over a period of
      180 days using the following instruments: OHI-S, DMF-T, the Fonnes brushing
      technique and diet questionnaire. Participants were divided into two groups
      according to level of co-operation on the programme: Group A (co-operative) and
      Group B (non-cooperative). A statistically significant improvement (p < 0.001) in
      Oral Hygiene was attained, with 84.2% showing regular or satisfactory hygiene at
      study end-point. CONCLUSION: Groups A and B both showed improvement in hygiene (p
      < 0.001 and p = 0.004), but improvement was significantly higher among co
      operative patients (p < 0.001 at 180 days), who also had a higher mean age (p =
      0.02).

PMID- 20052609
TI  - Association of existing and new candidate genes for anxiety, depression and
      personality traits in older people.
AB  - Genetic variants that have previously been associated with personality traits
      and/or psychological distress, or inflammatory marker levels were investigated
      for their relationship to self-rated personality traits, anxiety, and depression
      in two elderly Scottish cohorts. Ten genes (29 SNPs) were investigated in the
      Lothian Birth Cohort 1936 (approximately 70 years, N = 1,091). Four of these
      genes and seven others (35 SNPs) were tested in the Lothian Birth Cohort 1921 who
      were measured on the same traits and states on two occasions (approximately 80
      years, N = 550; 87 years, N = 229). For previously investigated candidate genes,
      some support (at a nominal significance level of 0.05/0.01) was found for
      association between NOS1 and personality traits (especially extraversion), PSEN1
      and depression/neuroticism, and GRIK3 and depression. Of the inflammatory marker
      candidate genes, TF showed some association with psychological distress. No SNPs
      withstood the correction to significance level for multiple testing.
      Nevertheless, the results will be of importance to future meta-analyses of these
      candidate genes in relation to psychological distress and personality.

PMID- 20052610
TI  - Estimating effect sizes in genome-wide association studies.
AB  - Knowledge about the proportion of markers without effects (p( 0 )) and the effect
      sizes in large scale genetic studies is important to understand the basic
      properties of the data and for applications such as the control of false
      discoveries and designing adequately powered replication studies. Many p(0)
      estimators have been proposed. However, high dimensional data sets typically
      comprise a large range of effect sizes and it is unclear whether the estimated
      p(0) is related to the whole range, including markers with very small effects, or
      just the markers with large effects. In this article we develop an estimation
      procedure that can be used in all scenarios where the test statistic distribution
      under the alternative can be characterized by a single parameter (e.g. non
      centrality parameter of the non-central chi-square or F distribution). The
      estimation procedure starts with estimating the largest effect in the data set,
      then the second largest effect, then the third largest effect, etc. We stop when
      the effect sizes become so small that they cannot be estimated precisely anymore
      for the given sample size. Once the individual effect sizes are estimated, they
      can be used to calculate an interpretable estimate of p(0). Thus, our method
      results in both an interpretable estimate of p(0) as well as estimates of the
      effect sizes present in the whole marker set by repeatedly estimating a single
      parameter. Simulations suggest that the effects are estimated precisely with only
      a small upward bias. The R codes that compute the effect estimates are freely
      downloadable from the website: http://www.people.vcu.edu/~jbukszar/.

PMID- 20052611
TI  - Prospective study of physical activity and risk of primary adenocarcinomas of the
      oesophagus and stomach in the EPIC (European Prospective Investigation into
      Cancer and nutrition) cohort.
AB  - OBJECTIVE: To analyse the association between types of physical activity
      (occupational, recreational and household, vigorous and overall) and risk of
      primary oesophageal (OAC) or gastric adenocarcinoma (GAC). METHODS: From nine
      European countries, 420,449 participants were recruited between 1991 and 2000 and
      followed-up for a mean of 8.8 years to register incident GAC and OAC. Information
      on physical activity (PA), diet, lifestyle and health-related variables was
      obtained at baseline. Helicobacter pylori infection status was considered in a
      subset of 1,211 participants. Analyses were repeated by tumour site (cardia/non
      cardia) and histological type (intestinal/diffuse). RESULTS: During the follow
      up, 410 GAC and 80 OAC occurred. A lower risk of overall and non-cardia GAC was
      found for increasing levels of a PA index which combined occupational PA with
      weekly time spent in sports and cycling. The hazard ratio (HR) of GAC was 0.69,
      95% CI: 0.50-0.94, for the comparison between active and inactive participants
      according to the PA index (HR = 0.44, 95% CI:0.26-0.74, for non-cardia GAC). No
      effect was found for cardia tumours or histological subtypes of GAC. PA of any
      kind was not associated with OAC. CONCLUSIONS: Overall and distal (non-cardia)
      gastric tumours were inversely associated with time spent on cycling and sports
      and a total PA index. No association was found for any type of PA and risk of
      cardia cancers of the stomach.

PMID- 20052612
TI  - Wet deposition of nitrogen and sulfur in Guangzhou, a subtropical area in South
      China.
AB  - With the aim of understanding the seasonal distribution of deposition fluxes of
      nitrogen (N) and sulfur (S) in South China, a main acid deposition region in
      China, precipitation samples were collected and analyzed from Guangzhou area,
      between March 2005 and February 2006. The estimated wet deposition of N
      (including ammonium nitrogen (NH(4)-N) and nitrate nitrogen (NO(3)-N)) and S
      (sulfate sulfur (SO(4)-S)) during the monitoring period were 40.47 kg N ha(-1)
      and 65.29 kg S ha(-1), respectively. The average deposition of NH(4)-N was ~1.5
      times of the NO(3)-N deposition, suggesting that the reduced and oxidized N
      depositions were comparable in the study area. The S and N depositions in the
      rainy season were greater than those in the dry season, showing great seasonal
      variation, which was consistent with both the distribution of precipitation and
      the period of fertilizer application for agriculture. The N and S wet deposition
      fluxes in Guangzhou were greater than those in Beijing and Zhengzhou, located in
      the northern China, but comparable to the level of Chongqing, located in the
      southwestern China, another major acid deposition region. The atmospheric N and S
      depositions in these cities from north to south were affected by both intensive
      agricultural and industrial activities.

PMID- 20052613
TI  - Impact of transport and industrial emissions on the ambient air quality of Lahore
      City, Pakistan.
AB  - Lahore's population is growing at a rate of 4% a year. It is widely perceived
      that because of this rapid growth, the level of services provided to the city's 7
      million inhabitants has substantially deteriorated. This study presents the
      finding of ambient air quality monitoring carried out in Lahore City, Pakistan.
      The ambient air quality was monitored for criteria pollutants carbon monoxide
      (CO), nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), ozone (O(3)), particulate
      matter (TSP and PM(10)), lead (Pb), and noise level at ten different locations of
      the city. The sampling locations were selected in a way to draw a representative
      profile of air quality, covering both newly developed as well as highly congested
      urban centers. The sulfur dioxide, lead, and suspended particulate concentration
      was found very high as compared to the ambient air quality standards of US
      Environmental Protection Agency and WHO guidelines. The 24-h average noise was
      exceeding the WHO limits at majority of the locations. The study presents the
      severity of air pollution in Lahore City, and findings would help city management
      to develop monitoring and mitigation measures to improve the air quality of the
      city.

PMID- 20052614
TI  - Accumulation of total trace metals due to rapid urbanization in microtidal zone
      of Pallikaranai marsh, South of Chennai, India.
AB  - The article presents the results for enrichment of total trace metals (TTMs) from
      Pallikaranai salt marsh in South Chennai, a metropolis on the southeast coast of
      India. TTMs Fe, Mn, Cr, Cu, Ni, Co, Pb, Zn, Cd, Sr, V, and Hg along with sediment
      texture, OC, and CaCO3 were analyzed in 36 surface sediments collected during
      August 2008 to recognize and observe the input of TTMs in the marsh from various
      sources in the city limits. In view of the rapid urbanization and
      industrialization in Chennai City, especially on the southern side, uncontrolled
      input of sewage, garbage, and industrial effluents into the Pallikaranai marsh
      land, the elevated concentrations are not surprising. The level of enrichment of
      TTMs has also increased by 20% to 60% for most of the elements when compared with
      all other ecosystems in the world as well as the nearby area. The results also
      indicate that the marshy region is more heavily contaminated with Cd, Hg, Cr, Cu,
      Ni, Pb, and Zn than other regions on the southeast coast of India. The Enrichment
      Factor, Contamination Factor, and I (geo) indexes are calculated, and these
      values are useful to assess the degree of pollution in sediments. The spatial
      distributions of TTMs are also controlled by other factors like geochemical,
      precipitation, and flocculation of particulate substances in the marsh. The
      results of the present study suggest the need for a regular monitoring and
      management program which will help to improve the quality of Pallikaranai
      pristine marsh land.

PMID- 20052615
TI  - IGF-1 and BMP-2 induces differentiation of adipose-derived mesenchymal stem cells
      into chondrocytes-like cells.
AB  - Articular cartilage defects are common, causing significant morbidities. Tissue
      engineering using pluripotent stem cells is a new promising modality for
      cartilage repair. In the current study, we investigated the chondrogenesis of
      rabbit adipose-derived stem cells (ADSCs). We isolated rabbit ADSCs and
      transfected these cells with constructs encoding human insulin growth like factor
      1 (IGF-1) and bone morphogenic protein 2 (BMP-2). We examined the growth and
      morphology of these transfected cells and their production of type II collagen
      and MMP-3. We found that IGF-1 and BMP-2 drove the chondrogenesis of ADSCs, which
      showed mature chondrocyte-like cells and formed cartilage nodules. These cells
      also produced type II collagen with a reduced production of MMP-3. Our findings
      suggested that human ADSCs could differentiate into chondrocyte-like cells driven
      by IGF-1 and BMP-2 and held promises as an abundant and ready source of stem
      cells for cartilage repair and regeneration.

PMID- 20052616
TI  - Monitoring in vivo load transmission through an external fixator.
AB  - This work presents a portable non-invasive external fixator to assess and monitor
      fracture healing in real time. To evaluate the potential of this fixator, a
      transverse osteotomy was performed in the tibia of six adult sheep (mean age 3+/
      0.5 years and weight 63+/-5 kg). The fractures were stabilized by a specially
      designed unilateral external fixator, which was instrumented by means of a set of
      strain gauges. Strains in the external surface of the fixator were monitored
      during all the healing process. A wireless, remote monitoring of the implant was
      developed through a specially designed external telemetric device. The strain
      gauges were arranged in two different half-bridge Wheatstone configurations,
      allowing easy post-processing of the signal. Thus, bending loads were measured in
      two planes of the external fixator acting as a load cell. The load through the
      fixator was evaluated for the gait cycle during all the healing process. Full
      weight bearing of the injured leg was observed from the beginning. The load
      transmission mechanism in the fixator was quite similar in all operated tibias
      and radiographic images showed a successful healing in all animals. Although the
      fixator has only been tested in an animal model, after further testing this
      system may have clinical potential.

PMID- 20052617
TI  - High-resolution MR study of the relationship between superficial calcification
      and the stability of carotid atherosclerotic plaque.
AB  - In this study, we have aimed to evaluate the relationship between the shape and
      location of superficial calcification and the presence of fibrous cap rupture and
      intraplaque hemorrhage in atherosclerotic carotid plaque. Sixty-three patients
      with carotid stenosis underwent contrast-enhanced high resolution MR examinations
      with a 3-T MR scanner and 226 slices with superficial calcification were
      evaluated in the study. The shape of superficial calcification was categorized as
      the irregular type (dotted/arcuated) and patchy type and the location of
      superficial calcification was categorized as the marginal type and central type.
      Intraplaque hemorrhage and fibrous cap rupture depicted on the same slice as
      superficial calcification were identified. The chi-squared test was used for
      statistical analysis. A total of 149 slices (65.9%) with intraplaque hemorrhage
      and 107 slices(47.3%)with fibrous cap rupture were detected. There were 191
      slices with irregular type (dotted/arcuated) calcification and 166 slices with
      marginal type calcification. Irregular superficial calcification was found more
      frequently accompanied with intraplaque hemorrhage as compared to the patchy type
      (73.8 vs. 22.9%, P < 0.0001); there was a significant difference between the
      marginal type and the central type for the accompaniment of intraplaque
      hemorrhage (72.9 vs. 46.7%, P < 0.05). However, there was no significant
      difference between different shapes and locations of superficial calcification
      that accompanied with fibrous cap rupture (P > 0.05). This study showed that
      superficial calcification is an important factor for determination of instability
      of atherosclerotic carotid plaque. The shape and location of superficial
      calcification are important features associated with the occurrence of
      intraplaque hemorrhage.

PMID- 20052618
TI  - How reliable are 40 MHz IVUS and 64-slice MDCT in characterizing coronary plaque
      composition? An ex vivo study with histopathological comparison.
AB  - The present study investigated whether IVUS could serve as a reliable reference
      in validating MDCT characterization of coronary plaque against a histological
      gold standard. Twenty-one specimens were postmortem human coronary arteries.
      Coronary cross-sections were imaged by 40 MHz IVUS and by 64-slice MDCT and
      characterized histologically as presenting calcified, fibrous or lipid-rich
      plaques. Plaque composition was analyzed visually and intra-plaque MDCT
      attenuation was measured in Hounsfield Units (HU). 83 atherosclerotic plaques
      were identified. IVUS failed to characterize calcified plaque accurately, with a
      positive predictive value (ppv) of 75% versus 100% for MDCT. Lipid-rich plaque
      was even less accurately characterized, with ppv of 60 and 68% for IVUS and MDCT
      respectively. Mean MDCT attenuation was 966 +/- 473 HU for calcified plaque, 83
      +/- 35 HU for fibrous plaque and 70.92 HU +/- 41 HU for lipid-rich plaque. No
      significant difference in mean MDCT attenuation was found between fibrous and
      lipid-rich plaques (P = 0.276). In vivo validation of MDCT against an IVUS
      reference thus appears to be an unsuitable and unreliable approach: 40 MHz IVUS
      suffers from acoustic ambiguities in plaque characterization, and 64-slice MDCT
      fails to analyze plaque morphology and components accurately.

PMID- 20052619
TI  - Stakeholder benefit from depression disease management: differences by rurality?
AB  - Despite increasing consensus about the value of depression disease management
      programs, the field has not identified which stakeholders should absorb the
      relatively small additional costs associated with these programs. This paper
      investigates whether two proposed stakeholders (health plans and employer
      purchasers) economically benefit from depression care management (reduced
      outpatient utilization and work costs, respectively) in two delivery systems
      (rural and urban). This study examined the main and differential effects of
      depression care management on outpatient utilization and work costs over 24
      months in a preplanned secondary analysis of 479 depressed patients from rural
      and urban primary care practices in a randomized controlled trial. Over 24
      months, the intervention did not significantly reduce outpatient utilization
      costs in the entire cohort (-$191, 95% confidence interval (CI)=-$2,083 to
      $1,647), but it did decrease work costs (-$1,970, 95% CI=-$3,934 to -$92). While
      not statistically significant, rural-urban differences in work costs were in the
      same direction, while rural-urban differences in utilization costs differed in
      direction. These findings provide preliminary evidence that employers who elect
      to cover depression care management costs should receive comparable economic
      benefits in the rural and urban employees they insure. Given the limited sample
      size, further research may be needed to determine whether health plans who elect
      to cover depression care management costs will receive comparable economic
      benefits in the rural and urban enrollees they insure.

PMID- 20052620
TI  - Social integration of people with serious mental illness: network transactions
      and satisfaction.
AB  - Social integration involves a process through which an individual establishes and
      maintains meaningful interpersonal relationships characterized by mutual exchange
      with community members in nonclinical settings. Using self-report data from a
      probability sample (n=252) of supportive independent housing residents,
      transactional (i.e., support exchanges) characteristics of social networks,
      paying particular attention to reciprocation of exchanges between residents and
      their network members, were analyzed. The study also examined the extent to which
      transactional characteristics are related to satisfaction with social relations.
      Findings indicated considerable reciprocity in social relationships. Controlling
      for sociodemographic variables and network structure characteristics, mutual
      exchanges of tangible and problem-solving support were positively associated with
      network satisfaction. Results suggest that supported socialization services aimed
      at network and resource development with this population could facilitate more
      frequent exchanges of tangible resources and problem-solving opportunities
      between consumers and network members, which, in turn, might promote social
      integration.

PMID- 20052621
TI  - Staffing challenges and strategies for organizations serving individuals who have
      experienced chronic homelessness.
AB  - Hiring and retaining appropriate staff is essential for programs serving those
      who have experienced chronic homelessness. This paper describes specific staffing
      challenges and strategies from the Collaborative Initiative to Help End Chronic
      Homelessness (CICH), an 11-site, multi-agency Federal program designed to serve
      people experiencing chronic homelessness who also have a disabling condition such
      as substance use or mental health problems. This paper addresses approaches to
      staffing including team structures, staff supervision, and training. Challenges
      identified include low pay, high rates of burnout and turnover, limited time for
      supervision, and multiple staff training needs. This paper also explores specific
      staffing strategies based on the experience of the CICH sites, and concludes with
      implications for practice, research, and policy, including recommendations for
      ongoing staff training, suggestions for future mixed-methods research, and a call
      for an enhanced focus on strengthening the homeless services workforce.

PMID- 20052622
TI  - The abdominal smile sign.

PMID- 20052623
TI  - Usefulness of serum procalcitonin levels for the early diagnosis of stroke
      associated respiratory tract infections.
AB  - BACKGROUND: Patients with extensive brain infarcts are at increased risk for
      stroke-associated respiratory tract infections (SARTI), which cause worse
      outcome. The benefit of general antibiotic prophylaxis is controversial. Early
      diagnosis of SARTI may improve patient selection for antimicrobial therapy.
      Procalcitonin (PCT) is widely recognized as serum marker for bacterial
      infections. Its diagnostic value with respect to SARTI has not been assessed
      systematically. METHODS: Serum PCT levels were analyzed in ischemic stroke
      patients (n = 50) at day 1 (d1) and day 4 (d4) after stroke onset. PCT test
      performance was assessed by receiver operator characteristics (ROC) curve
      analysis. Multivariable logistic regression analysis was applied to identify
      early predictors for SARTI. RESULTS: Higher d4 serum PCT levels were associated
      with SARTI; ROC curve analysis revealed an area under the curve (AUC) of 0.79
      (95%-confidence interval (CI) 0.61-0.96). A 0.25-ng/ml cutoff resulted in a test
      sensitivity and specificity of 42 and 96%, respectively. Positive (LR+) and
      negative (LR-) likelihood ratios were 10.8 and 0.6, respectively. In predicting
      SARTI, multivariable logistic regression analysis controlling for infarct volume
      ruled out an independent explanatory effect of serum PCT. Greater infarct volume
      (odds ratio (OR) 1.06, 95%-CI 1.02-1.1) prevailed as independent SARTI-predictor.
      CONCLUSIONS: In the absence of clinical signs, post-stroke screening for SARTI
      using serum PCT levels is not useful since test sensitivity is low. If the
      clinical suspicion for SARTI is strong, serum PCT-testing (>0.25 ng/ml) may
      improve diagnostic accuracy by improving specificity.

PMID- 20052624
TI  - Severe alcohol hand rub overdose inducing coma, watch after H1N1 pandemic.
AB  - BACKGROUND: Alcoholic hand rubs (AHRs) have been proven effective in preventing
      nosocomial infections, and healthcare authorities include AHRs use among quality
      of-care criteria. Since the onset of the influenza A (H1N1) pandemic, AHRs have
      gained considerable popularity among the general public. METHODS: We report a
      case of intentional AHRs self-poisoning inducing rapid coma with hyperlactatemia,
      and a full recovery. The relevant literature was reviewed. To our knowledge, this
      is the third reported case of intentional AHRs poisoning. 3 patients presented
      with a picture of acute alcohol intoxication, of variable severity depending on
      the amount ingested and speed of ingestion. RESULTS: The blood alcohol level was
      414 mg/dl and tests for other drugs were performed 30 min after admission. The
      blood lactate level increased briefly to 4.8 mmol/l, without renal or hepatic
      function disturbances. She regained consciousness after 6 h then achieved a full
      recovery allowing extubation and readmission to the psychiatric ward after 24 h.
      She reported gulping down the entire contents of the Aniosgel bottle. CONCLUSION:
      Whereas overdrinking in social settings (wine and liquor) leads to a gradual
      increase in blood alcohol levels, AHRs poisoning is usually characterized by a
      sudden massive alcohol load. The unusual nature of the alcohol source may lead to
      diagnostic wanderings. AHRs are currently available in bottles that facilitate
      the ingestion of large amounts. Unit-dose packaging or dispensing might decrease
      the risk of AHRs poisoning.

PMID- 20052625
TI  - SVEP1 is a novel marker of activated pre-determined skeletal muscle satellite
      cells.
AB  - In this study we explored the expression pattern of SVEP1, a novel cell adhesion
      molecule (CAM), in bona fide satellite cells and their immediate progeny. We show
      that SVEP1 is expressed in activated satellite cells prior to their determination
      to the myogenic lineage. SVEP1 was also expressed during early phases of myogenic
      differentiation through the initial stage of myoblast fusion and myotube
      formation. The expression of SVEP1 was shown by immunostaining two cell culture
      systems: freshly isolated myofibers and primary myoblasts. Pax7 was used to
      pinpoint satellite cells situated in their niche on myofibers, and activated
      satellite cells were determined based on BrdU incorporation
      (Pax7(+)/BrdU(+)cells). MyoD marked satellite cells fated to undergo myogenesis
      as well as proliferating and differentiating myoblasts. Differentiating myoblasts
      and myotubes were identified based on their sarcomeric myosin expression. We
      showed that SVEP1 was specifically expressed in pre-determined activated
      satellite cells (Pax7(+)/ BrdU(+) /MyoD(-)) accounting for about 24% of total
      satellite cells. On the other hand, SVEP1 expression was absent in quiescent
      satellite cells (Pax7(+)/BrdU(-)/MyoD(-)). Moreover, based on MyoD/sarcomeric
      myosin co-expression SVEP1 was shown to be expressed throughout the early phases
      of myogenesis up until myoblast fusion and myotube formation. A decline in SVEP1
      expression occurred upon myotube maturation. We suggest SVEP1 as a potential
      biomarker for pre-fated satellite cells. The impact of this finding is that it
      may allow scrutinizing signals that affect differentiation commitment. Thus,
      holds a therapeutic potential for maladies that involve deregulated stem cell
      fate-decision.

PMID- 20052626
TI  - Endotracheal cuff leakage: a simple solution for an occasionally serious problem.

PMID- 20052627
TI  - Ultrasound-guided suprascapular nerve block: a correlation with fluoroscopic and
      cadaveric findings.
AB  - PURPOSE: Previous work on the ultrasound-guided injection technique and the
      sonoanatomy of the suprascapular region relevant to the suprascapular nerve (SSN)
      block suggested that the ultrasound scan showed the presence of the suprascapular
      notch and transverse ligament. The intended target of the ultrasound-guided
      injection was the notch. The objective of this case report and the subsequent
      cadaver dissection findings is to reassess the interpretation of the ultrasound
      images when locating structures for SSN block. CLINICAL FEATURES: A 45-yr-old man
      with chronic shoulder pain received an ultrasound-guided SSN block using the
      suprascapular notch as the intended target. The position of the needle was
      verified by fluoroscopy, which showed the tip of the needle well outside the
      suprascapular notch. Similar ultrasound-guided SSN blocks were performed in two
      cadavers. Dissections were performed which showed that the needle tips were not
      at the suprascapular notch but, more accurately, were close to the SSN but at the
      floor of the suprascapular fossa between the suprascapular and spinoglenoid
      notch. CONCLUSION: Our fluoroscopic and cadaver dissection findings both suggest
      that the ultrasound image of the SSN block shown by the well-described technique
      is actually targeting the nerve on the floor of the suprascapular spine between
      the suprascapular and spinoglenoid notches rather than the suprascapular notch
      itself. The structure previously identified as the transverse ligament is
      actually the fascia layer of the supraspinatus muscle.

PMID- 20052628
TI  - Walking epidurals for labour analgesia: do they benefit anyone?

PMID- 20052629
TI  - [Maximal torque and muscle activation in different angular positions for trunk
      flexion, extension and rotation].

PMID- 20052630
TI  - Effect of race and ethnicity classification on survey estimates: Anomaly of the
      weighted totals of American Indians and Alaska Natives.
AB  - Racial classification is a paramount concern in data collection and analysis for
      American Indians and Alaska Natives (AI/ANs) and has far-reaching implications in
      health research. We examine how different racial classifications affect survey
      weights and consequently change health-related indicators for the AI/AN
      population in California. Using a very large random population-based sample of
      AI/ANs, we compared the impact of three weighting strategies on counts and rates
      of selected health indicators. We found that different weights examined in this
      study did not change the percentage estimates of health-related variables for
      AI/ANs, but did influence the population total estimates dramatically. In survey
      data, different racial classifications and tabulations of AI/ANs could yield
      discrepancies in weighted estimates for the AI/AN population. Policy makers need
      to be aware that the choice of racial classification schemes for this racial
      political group can generally influence the data they use for decision making.

PMID- 20052632
TI  - Preliminary assessment of Apache hopefulness: Relationships with hopelessness and
      with collective as well as personal self-esteem.
AB  - Hopelessness is central to prominent mental health problems within American
      Indian (AI) communities. Apaches living on a reservation in Arizona responded to
      diverse expressions of hope along with Hopelessness, Personal Self-Esteem, and
      Collective Self-Esteem scales. An Apache Hopefulness Scale expressed five themes
      of hope and correlated negatively with Hopelessness and positively with both
      Collective and Personal Self-Esteem. These data confirmed the potential of
      conducting more extensive analyses of hope within AI tribal life.

PMID- 20052631
TI  - Depressed affect and historical loss among North American Indigenous adolescents.
AB  - This study reports on the prevalence and correlates of perceived historical loss
      among 459 North American Indigenous adolescents aged 11-13 years from the
      northern Midwest of the United States and central Canada. The adolescents
      reported daily or more thoughts of historical loss at rates similar to their
      female caretakers. Confirmatory factor analysis indicated that our measure of
      perceived historical loss and the Center for Epidemiologic Studies Depression
      scale were separate but related constructs. Regression analysis indicated that,
      even when controlling for family factors, perceived discrimination, and proximal
      negative life events, perceived historical loss had independent effects on
      adolescents' depressive symptoms. The construct of historical loss is discussed
      in terms of Indigenous ethnic cleansing and life course theory.

PMID- 20052633
TI  - [Vitamin B 12 deficiency].

PMID- 20052634
TI  - [What is your diagnosis? Urothelial carcinoma pT1. Retroperitoneal cyst of
      unknown etiology].

PMID- 20052635
TI  - [Data on overweight and nutrition in the 2007 Swiss Health Survey].
AB  - The 2007 Swiss Health Survey is the fourth survey conducted by the Federal Office
      of Statistics in intervals of five years. Data are collected from a random sample
      (n = 18760) of persons aged 15 and over, living in Switzerland: 29% are
      overweight, and additional 8% are obese, but between 2002 and 2007 no increases
      in the prevalence of overweight and obesity were observed anymore. In relation to
      nutritional habits, nearly 30% of the interviewed persons do not care about their
      nutrition. Only 30% of the population eat the recommended five portions of fruits
      and vegetables per day, and only 10% consume the recommended three servings of
      milk and milk products. 37% do rarely or never consume fish. Nearly 20% eat meat
      or meat products every day. According to the four Swiss Health Surveys
      nutritional habits have hardly improved during the last fifteen years in
      Switzerland.

PMID- 20052636
TI  - [Comment on rule of thumb 7. "Groaning during blood pressure determination:
      suspected somatoform pain].

PMID- 20052637
TI  - [Trigeminal neuralgia - pathophysiology, clinical aspects and treatment].
AB  - The trigeminal neuralgia is characterised by paroxysmal appearing fulgurous
      stabbing pain. Its medical condition is caused through a local-circumscribed
      demyelinisation of the trigeminal nerve with consecutive conduction of salting
      impulses on afferent pain fibres. It is essential to differentiate the
      symptomatic from the idiopathic trigeminal neuralgia. As primary management, a
      pharmacological treatment with anticonvulsants is recommended in order to
      attenuate the ectopic-generated pain impulses. Different neurosurgical procedures
      are available in cases of resistance to therapy. Thereby, causal surgery in form
      of microvascular decompression is not only the operative treatment of choice, but
      because of the excellent results also a fundamental support of the theory of
      vascular compression. A comprehensive knowledge about diagnosis and management of
      trigeminal neuralgia is essential to treat patients efficiently and successfully.
      This synopsis summarises the current recommendations concerning diagnostics and
      therapeutic options.

PMID- 20052638
TI  - [Torsion of a pedunculated subserous myoma - a rare differential diagnosis of the
      acute abdomen].
AB  - We report about a rare case of acute abdomen in a 43 years old female patient who
      noticed a sudden onset of severe lower abdominal pain, increasing in strength
      within a few hours. The transabdominal and transvaginal ultrasound showed an
      enlarged leiomyomatous uterus with a questionable torsion of a pedunculated
      subserous leiomyoma. The following magnetic resonance imaging confirms this
      diagnosis. During the laparoscopy a myomectomy has been performed.

PMID- 20052639
TI  - [Decreased sexual desire in women].

PMID- 20052640
TI  - [Abdominal tumor after persistent coughing and uncontrolled anticoagulation].
AB  - We report the case of a 83-year-old female patient with ST elevation myocardial
      infarction who developed a rectus sheath hematoma during treatment with
      antiplatelet medication and systemic anticoagulants following cough attacks. The
      patient presented with progressive pain in the left lower abdomen associated with
      a palpable mass and anaemia. Abdominal sonography and computed tomography
      revealed a rectus sheath hematoma. We discuss pathogenesis, clinical findings,
      diagnostic workup and therapy. Moreover, we review the current related
      literature.

PMID- 20052641
TI  - [Peripheral facial palsy accompanied by a vesicular rash on the ear and hard
      palate].
AB  - Ramsay Hunt syndrome (RHS) is defined as a peripheral facial nerve palsy
      accompanied by an erythematous vesicular rash on the ear (zoster oticus) and hard
      palate. It is known that varicella zoster virus (VZV) causes RHS. History and
      neurological examination remain the mainstay of diagnosis. Prednisolone and
      acyclovir/valacyclovir is helpful in RHS when given within three days of onset.
      We report on a 14-year-old boy who had RHS accompanied by meningitis. Polymerase
      chain reaction identified VZV in exudates from the geniculate zone of the ear,
      the hard palate and in the CSF.

PMID- 20052642
TI  - [Type of diet has no effect on long-term weight loss].

PMID- 20052643
TI  - [Efficacy of steroids and antiviral agents in patients with facial paralysis].

PMID- 20052646
TI  - [Physician art column].

PMID- 20052647
TI  - [Physician literature puzzle].

PMID- 20052648
TI  - [Female pelvic floor insufficiency: the benefit of general practitioner -
      urogynecologist interaction].
AB  - Incontinence for urine and stool as well as genital prolapse and pain has been
      widely discussed in public media. Nevertheless patients suffering from these
      problems are still not ready to actively seek help. Therefore the general
      practitioner plays a major role to identify these women especially when medical
      help is necessary. According to the guidelines of the International Consultation
      of Incontinence the general practitioner also plays a major role when it comes to
      basic treatment options. Networking these patients with the urogenecology
      specialist is mandatory in order to get the best results possible for an
      individual patient.

PMID- 20052649
TI  - [Influence of pregnancy and delivery to the pelvic floor].
AB  - One third of women will suffer from urinary incontinence 3 to 6 months after
      birth, one in ten from anal incontinence and one percent from prolapse. The risk
      for uterine prolapse increases with future vaginal pregnancies, an indication for
      an elective cesarean section however must be balanced based on the multifactorial
      nature and the low prevalence of prolapse against the risks of a cesarean section
      especially of placental pathology in future pregnancies. The correlation between
      mode of delivery and urinary incontinence decreases with increasing number of
      pregnancies and with follow up after 65 years. Anal incontinence depends mostly
      from the mode of delivery and occurs often in combination with a high sphincter
      laceration or damage of the pudendus nerve. Due to different definitions and
      populations and lack of randomised studies the prevalence and risk calculations
      are divergent. In the absence of evidence and the presence of established
      placental risks in future pregnancies a general recommendation for an elective
      caesarean section is not justified. Decisions on the mode of delivery can be
      complex which is why established risk factors, life style factors and preventive
      evidence based methods are important informations for the antenatal care
      consultation. To identify women with a high risk for pelvic floor disorders is
      part of ongoing research.

PMID- 20052650
TI  - [Urinary incontinence].
AB  - Incontinence is a common age-dependent and increasing problem in women that may
      mainly present as stress incontinence, overactive bladder, mixed incontinence or
      other forms. A thorough history, gynaecological and neurological examination and
      urinalysis as initial step will lead to the diagnosis and treatment. If midstream
      urine is difficult to receive, a catheter urine will be easy to obtain. Further
      investigations as urodynamics, cystoscopy and ultrasound may be required. As
      initial step, stress incontinence should be treated with physiotherapy and pelvic
      floor exercises, if not successful with operations as suburethral slings. Slings
      have good long-term success rates of approximately 85 % with a low morbidity and
      can even be inserted under local anaesthetic. The treatment of idiopathic
      overactive bladder consists of bladder training, a behavioural therapy, and
      mainly anticholinergics. Anticholinergics may cause side effects particularly in
      the elderly who are under several medications that may add anticholinergic
      effects as antidepressants, antibiotics or antihistaminics.

PMID- 20052651
TI  - [Aging-related changes of the female pelvic floor].
AB  - The pelvic floor as lower closure of the abdominal cavity has to withstand the
      abdominal pressure. Meanwhile, the pelvic floor has to allow physiologic
      functions like micturition, defecation, sexual function and reproduction. But
      while pregnancy and vaginal delivery damage the pelvic floor directly, chronic
      stress like caugh, heavy lifting, or obesity lead to a chronic overstraining of
      the pelvic floor. Aging, structural changes, and possibly estrogen deficiency
      have a negative impact on the pelvic floor.

PMID- 20052652
TI  - [Pelvic floor insuffiency - conservative treatments].
AB  - Conservative treatments are easy to handle, have no side effects and no negative
      effects concerning later surgical treatments and are not expensive. Therefore
      conservative treatments should be the first line therapies for pelvic floor
      disorders. The following treatment options are used: lifestyle interventions,
      bladder training, use of pessaries, pelvic floor muscle training, pharmacologic
      treatment, incontinence aids/products and complementary medicine. Important for
      the success of these treatments are motivation and patience of the patient as
      well a good team consisting of doctors, specialised nurses and physiotherapists.
      Usually all these treatments are combined. The success rate is between 40-70 %.
      Pessaries are the best choice for immediate relief of urinary stress incontinence
      and for reducing a prolapse.

PMID- 20052653
TI  - [Reconstructive surgery of female pelvic floor prolapse].
AB  - It is recommended to perform pelvic floor prolapse surgery within a concept which
      bases on the women's symptoms, the expectations on life quality and functional
      aspects of the vagina, urinary bladder and rectum. Decisions on type of surgery
      must also be founded on the anatomical defect. An apical prolapse should either
      be fixed by sacrospinous ligament suspension or by sacrocolpopexy. In case of a
      cystocele the type of defect must be considered; a cystocele with a central
      defect can be corrected by anterior colporrhaphy whereas the cystocele caused by
      a paravaginal defect needs lateral fixation which today is increasingly done by
      vaginal mesh surgery. Rectocele repair is performed by posterior colporrhaphy.
      Knowledge of success and complication rates is essential for taking the right
      surgical decisions and for counselling the patient.

PMID- 20052654
TI  - [Fecal incontinence].
AB  - Fecal incontinence is underestimated in its prevalence. Therapeutic approaches
      vary; in mild-to-moderate cases, dietary changes and biofeedback sessions
      accompanied by specific medications can achieve a salutary effect. In cases of
      severe fecal incontinence, a conservative approach is ineffective and surgical
      intervention is indicated. However, several technical innovations and devices
      enable surgeons to offer patients reliable solutions for this functional
      disorder. While dynamic graciloplasty uses native muscle contraction ability to
      function as a new sphincter, the artificial bowel sphincter achieves the same
      goal by an inflatable cuff. A novel approach, which is suitable for selected
      patients with muscular and neurological defects alike, is the sacral nerve
      stimulator. It is crucial to choose the right procedure as determined by the
      underlying pathology.

PMID- 20052655
TI  - [Female sexual dysfunction].
AB  - Female sexual dysfunction is common with a prevalence of 20 % to 50 %. Its
      etiology is multifactorial. Female sexual dysfunction is a complex neurovascular
      phenomenon, influenced by psychological, neurological, muscular and endocrine
      factors. In pelvic floor dysfunction sexual dysfunction is the result of
      anatomical und functional changes, as well as the therapy applied. Sexual
      dysfunction in urinary incontinence is frequent; its combination with prolaps has
      a negative cumulative effect. Pelvic floor surgery, irrespective of the surgical
      procedures, may lead to sexual dysfunction. An individualised approach to
      treatment is important when assessing and counselling women.

PMID- 20052656
TI  - Hepatocytes do not undergo epithelial-mesenchymal transition in liver fibrosis in
      mice.
AB  - The origin of fibrogenic cells in liver fibrosis remains controversial. We
      assessed the emerging concept that hepatocytes contribute to production of
      extracellular matrix (ECM) in liver fibrosis through epithelial-mesenchymal
      transition (EMT). We bred triple transgenic mice expressing ROSA26 stop beta
      galactosidase (beta-gal), albumin Cre, and collagen alpha1(I) green fluorescent
      protein (GFP), in which hepatocyte-derived cells are permanently labeled by beta
      gal and type I collagen-expressing cells are labeled by GFP. We induced liver
      fibrosis by repetitive carbon tetrachloride (CCl(4)) injections. Liver sections
      and isolated cells were evaluated for GFP and beta-gal as well as expression of
      alpha-smooth muscle actin (alpha-SMA) and fibroblast-specific protein 1 (FSP-1).
      Upon stimulation with transforming growth factor beta-1, cultured hepatocytes
      isolated from untreated liver expressed both GFP and beta-gal with a fibroblast
      like morphological change but lacked expression of other mesenchymal markers.
      Cells from CCl(4)-treated livers never showed double-positivity for GFP and beta
      gal. All beta-gal-positive cells exhibited abundant cytoplasm, a typical
      morphology of hepatocytes, and expressed none of the mesenchymal markers
      including alpha-SMA, FSP-1, desmin, and vimentin. In liver sections of CCl(4)
      treated mice, GFP-positive areas were coincident with fibrotic septa and never
      overlapped X-gal-positive areas. CONCLUSION: Type I collagen-producing cells do
      not originate from hepatocytes. Hepatocytes in vivo neither acquire mesenchymal
      marker expression nor exhibit a morphological change clearly distinguishable from
      normal hepatocytes. Our results strongly challenge the concept that hepatocytes
      in vivo acquire a mesenchymal phenotype through EMT to produce the ECM in liver
      fibrosis.

PMID- 20052657
TI  - Invasive growth of Saccharomyces cerevisiae depends on environmental triggers: a
      quantitative model.
AB  - In this contribution, the influence of various physicochemical factors on
      Saccharomyces cerevisiae invasive growth is examined quantitatively. Agar
      invasion assays are generally applied for in vitro studies on S. cerevisiae
      invasiveness, the phenomenon observed as a putative virulence trait in this
      clinically more and more concerning yeast. However, qualitative agar-invasion
      assays, used until now, strongly limit the feasibility and interpretation of
      analyses and therefore needed to be improved. Besides, knowledge in this field
      concerning the physiology of invasive growth, influenced by stress conditions
      related to the human alimentary tract and food, is poor and should be expanded.
      For this purpose, a quantitative agar-invasion assay, presented in our previous
      work, was applied in this contribution to clarify the significance of the stress
      factors controlling the adhesion and invasion of the yeast in greater detail. Ten
      virulent and non-virulent S. cerevisiae strains were assayed at various
      temperatures, pH values, nutrient starvation, modified atmosphere, and different
      concentrations of NaCl, CaCl2 and preservatives. With the use of specific
      parameters, like a relative invasion, eight invasive growth models were
      hypothesized, which enabled intelligible interpretation of the results. A strong
      preference for invasive growth (meaning high relative invasion) was observed when
      the strains were grown on nitrogen- and glucose-depleted media. A significant
      increase in the invasion of the strains was also determined at temperatures
      typical for human fever (37-39 degrees C). On the other hand, a strong repressive
      effect on invasion was found in the presence of salts, anoxia and some
      preservatives.

PMID- 20052658
TI  - A technical tip on scanning obese gravidae.

PMID- 20052659
TI  - Placental growth factor in the first trimester: relationship with maternal
      factors and placental Doppler studies.
AB  - OBJECTIVE: Placental growth factor (PlGF) is a potent angiogenic factor that
      impacts on early placental vascular development. It was our aim to clarify
      relationships between PlGF and first-trimester maternal/placental factors that
      are related to placental development. METHODS: Prospectively enrolled patients at
      11-14 weeks' gestation had serum PlGF measurement by enzyme-linked immunosorbent
      assay. Results were related to maternal age, parity, race, body mass index, mean
      arterial blood pressure (MAP), smoking/caffeine use and parameters of placental
      blood flow resistance. RESULTS: In 110 consecutive patients PlGF levels ranged
      between 1.0 and 176.1 pg/mL, showing a linear relationship with gestational age
      (GA) (PlGF = (1.4251 x GA) -74.951, r(2) = 0.0765, F = 8.941, P = 0.03). PlGF did
      not relate to maternal demographics but negatively correlated with MAP (Spearman
      rho = -0.191, P < 0.05). Bilateral uterine artery notching was associated with
      lower PlGF (40.7 (range, 1.01-131.6) vs. 51.1 (range, 6.4-176.1) pg/mL; Mann
      Whitney P = 0.034.). A trend to lower levels was also observed when umbilical
      artery end-diastolic flow was absent (37.1 (range, 6.8-95) vs. 49.3 (range, 1.01
      176.1) pg/mL; P = 0.05). CONCLUSION: PlGF in the first trimester is related to
      maternal cardiovascular factors and placental Doppler findings that are
      associated with subsequent placental dysfunction. The utility of this parameter
      as a first-trimester screening tool on a population basis requires further
      investigation.

PMID- 20052660
TI  - Comparison of first-trimester contingent screening strategies for Down syndrome.
AB  - OBJECTIVE: To assess the relative performance of a multi-stage first-trimester
      screening protocol for fetal Down syndrome. METHODS: Data from 10,767 women who
      underwent combined ultrasound and biochemistry (BC) screening in the first
      trimester were reanalyzed using a contingent model approach. Amongst the 10,854
      fetuses with known outcome, 32 had Down syndrome, 232 had other abnormalities and
      10,590 were unaffected. Nuchal translucency (NT), BC and combined (NT-BC)
      gestational age-specific risks were calculated for each individual using The
      Fetal Medicine Foundation risk calculation algorithms (Mixture Model and
      Biochemistry). Individual patients were categorized as at low, high or
      intermediate risk according to one of the following three strategies. In
      'Strategy-NT-BC' initial screening was performed using both NT and BC. In
      'Strategy-BC' initial screening was undertaken using maternal serum markers
      followed by NT assessment in those with an intermediate risk (1 : 51 < risk <or=
      1:1000) while in 'Strategy-NT' initial screening was undertaken using NT followed
      by serum marker assessment in those with an intermediate risk (1 : 51 < risk <or=
      1:1000). The nasal bone was assessed in those with an intermediate risk as the
      final stage in each of the three strategies. Those with an adjusted risk of 1 in
      100 or higher after nasal bone assessment were reclassified as high risk.
      Detection and false-positive rates were compared between differing strategies in
      our local population, and this analysis was also performed with the maternal age
      for our population standardized to the distribution found in England and Wales.
      RESULTS: In our local population the detection rate for a 5% false-positive rate
      using a combined screening policy (NT-BC) was 88% (95% CI, 75.3-98.9%), and 2.3%
      had an absent nasal bone. The respective detection rate and false-positive rate
      of the three multi-stage screening strategies were: Strategy-NT-BC: 87.5 and
      2.5%; Strategy-BC: 87.5 and 5%; Strategy-NT: 84.4 and 2.9%. In the contingent
      Strategy-BC only 29% of those initially screened using serum markers required an
      NT scan. If the model were applied to a hypothetical obstetric population
      standardized to the maternal age distribution in England and Wales, the detection
      and false-positive rates of the same three screening strategies would be:
      Strategy-NT-BC: 86.2 and 1.9%; Strategy-BC: 82.8 and 4%; Strategy-NT: 75.8 and
      2.3%, respectively. CONCLUSION: First-trimester contingent screening provides
      detection and false-positive rates comparable to those achieved using combined
      screening, but could be used to significantly reduce the number of scans
      performed.

PMID- 20052661
TI  - Effectiveness of cerclage according to severity of cervical length shortening: a
      meta-analysis.
AB  - OBJECTIVES: To estimate the effectiveness of cerclage according to degree of
      cervical length (CL) shortening. METHODS: A meta-analysis was carried out of
      trials of women with singleton gestations and second-trimester transvaginal
      sonographic CL < 25 mm randomized to cerclage or no cerclage. The degree of CL
      shortening was correlated to the efficacy of cerclage in preventing preterm
      birth. RESULTS: There was a significant reduction in preterm birth < 35 weeks in
      the cerclage compared with no cerclage groups in 208 singleton gestations with
      both a previous preterm birth and CL < 25 mm (relative risk, 0.61; 95% CI, 0.40
      0.92). In these women, preterm birth < 37 weeks was significantly reduced with
      cerclage for CL < or = 5.9 mm, < or = 15.9 mm, 16-24.9 mm and < 25 mm. None of
      the analyses for 344 women without a previous preterm birth was significant.
      CONCLUSIONS: Cerclage, when performed in women with a singleton gestation,
      previous preterm birth and cervical length < 25 mm, seems to have a similar
      effect regardless of the degree of cervical shortening, including CL 16-24 mm, as
      well as CL < or = 5.9 mm.

PMID- 20052662
TI  - Abnormal first-trimester ductus venosus blood flow: a marker of cardiac defects
      in fetuses with normal karyotype and nuchal translucency.
AB  - OBJECTIVE: To evaluate the independent contribution of ductus venosus (DV) blood
      flow assessment at 11-14 weeks' gestation to the prediction of congenital heart
      defects (CHD) in chromosomally normal fetuses, irrespective of the value of the
      nuchal translucency thickness (NT). METHODS: During a 4-year period, all
      singleton pregnancies from 11 + 0 to 13 + 6 weeks' gestation were scanned for NT
      and DV blood flow in a tertiary center. Abnormal DV blood flow was defined as
      either absent or reversed flow during atrial contraction (AR-DV). Fetal
      echocardiography was performed in all cases with either NT > 99(th) percentile or
      AR-DV. Follow-up was assessed by postnatal examination or autopsy in cases of
      termination of pregnancy or perinatal death. RESULTS: A total of 6120 pregnancies
      were scanned at a median gestational age of 12 weeks, and 45 cases of CHD were
      detected. AR-DV was found in 206 fetuses, of which 145 (70.4%) had a normal
      karyotype. Among fetuses with AR-DV and normal karyotype, 11 cases of CHD were
      diagnosed, giving a sensitivity of 24.4%, a positive predictive value of 7.6% and
      an odds ratio of 9.8. Increased NT (> 99(th) centile) was present in 55 of the
      145 (37.9%) cases with AR-DV and normal karyotype, and in 6/11 (54.5%) of those
      with CHD. Thus, the group of 90 fetuses with abnormal DV blood flow and normal NT
      contained five cases of CHD, for a sensitivity of 11.1%, a positive predictive
      value of 5.5% and an odds ratio of 8.5. Right-heart anomalies were predominant in
      those cases with isolated AR-DV (4/5), but no specific CHD pattern was found in
      those with increased NT. The detection rate of CHD by the combined use of
      increased NT and/or AR-DV in the first trimester improved from 28.9% (13/45) to
      40.0% (18/45). CONCLUSIONS: In experienced hands, abnormal DV blood flow in the
      first trimester is an independent predictor of CHD and should constitute an
      indication for early echocardiography. In this study, the use of DV blood flow
      assessment increased early detection of CHD by 11% with respect to the use of NT
      measurement alone.

PMID- 20052663
TI  - Continuous independent quality control for fetal ultrasound biometry provided by
      the cumulative summation technique.
AB  - OBJECTIVE: To apply the cumulative summation (CUSUM) technique for an evaluation
      of the learning process of sonographic fetal weight estimation at term in
      combination with the z-scores of biometry determinants and to assess the time of
      appearance and sources of errors. METHODS: Learning curve (LC-CUSUM) and double
      CUSUM charts for systematic error detection based on absolute and signed mean
      percentage error were generated to retrospectively estimate the longitudinal
      accuracy of sonographic fetal weight estimation conducted by three trainees and
      one experienced examiner. For LC-CUSUM analysis an examination was considered to
      be a failure when there was an absolute error in birth weight estimation >/= 15%.
      Fetal biometry measurements (head circumference, abdominal circumference (AC) and
      femur length (FL)) from 227 routine ultrasound scans of one examiner were
      separately transformed into z-scores and double CUSUM charts were generated to
      assess the systematic errors for each determinant. RESULTS: The LC-CUSUM charts
      revealed that different numbers of scans are required for different examiners to
      achieve competence in estimating birth weight. AC and FL deviated most
      significantly from expected values (P < 0.05). The double CUSUM charts revealed
      exact periods of systematic errors in the measurement of biometry determinants,
      clearly reflecting errors of fetal weight estimation. CONCLUSIONS: The use of
      CUSUM techniques in the analysis of sonographic data allows observation of the
      development of an examiner's skill and maintenance of competence. The CUSUM
      technique not only allows the reasons for impaired fetal weight estimation to be
      revealed but also allows determination of the exact time when inaccurate
      measurements start to occur. We suggest that CUSUM charts should be implemented
      in routine clinical practice as a measure of objective quality evaluation of
      sonographic fetal biometry.

PMID- 20052664
TI  - Brief communication: tissue isotopic enrichment associated with growth depression
      in a pig: implications for archaeology and ecology.
AB  - Stressors such as fasting or poor diet quality are thought to potentially alter
      the nitrogen and carbon isotopic values of animal tissues. In this study, we
      demonstrate an inverse correlation between growth rate and multiple tissue
      enrichment of delta(15)N, delta(13)C, and, to a lesser degree, delta(18)O in a
      juvenile pig. A more complex pattern is observed with respect to tissue deltaD
      and growth rate. The observed association between growth rate and tissue isotopic
      fractionation has important implications for paleodietary and migratory
      reconstructions of archaeological populations that may have been affected by
      famine, malnutrition, seasonal variation in food availability, and/or other
      factors that can affect childhood growth rates.

PMID- 20052665
TI  - Three-dimensional ultrasound in the diagnosis of Mullerian duct anomalies and
      concordance with magnetic resonance imaging.
AB  - OBJECTIVES: To demonstrate the value of three-dimensional (3D) ultrasound in the
      diagnosis of uterine malformations and its concordance with magnetic resonance
      imaging (MRI). METHODS: This study included 286 women diagnosed with uterine
      malformation by 3D ultrasound, having been referred to our clinics on suspicion
      of uterine malformation following clinical and/or conventional two-dimensional
      ultrasound examination. With the exception of three with intact hymen, patients
      underwent both bimanual examination and speculoscopy before and/or after
      sonography. MRI was performed in 65 cases. We analyzed the diagnostic concordance
      between the techniques in the study of uterine malformations. RESULTS: Using 3D
      ultrasound we diagnosed: one case with uterine agenesis; 10 with unicornuate
      uterus, four of which also underwent MRI; six with didelphic uterus, one of which
      had MRI; 45 with bicornuate uterus, 12 of which had MRI; 125 with septate uterus
      (18 with two cervices), 42 of which had MRI (six with two cervices); 96 with
      arcuate uterus, three of which had MRI; and three with diethylstilbestrol (DES)
      iatrogenic uterine malformations, all of which had MRI. Among the 65 which
      underwent MRI, the diagnosis was: four cases with unicornuate uterus, 10 with
      bicornuate uterus (two with two cervices), 45 with septate uterus (five with two
      cervices), three with arcuate uterus and three with DES-related uterine
      malformations. The concordance between 3D ultrasound and MRI was very good (kappa
      index, 0.880 (95% CI, 0.769-0.993)). Discrepancies in diagnosis between the two
      techniques occurred in four cases. There was very good concordance in the
      diagnosis of associated findings (kappa index, 0.878 (95% CI, 0.775-0.980)), this
      analysis identifying differences in two cases. CONCLUSIONS: There is a high
      degree of concordance between 3D ultrasound and MRI in the diagnosis of uterine
      malformations, the relationship between cavity and fundus being visualized
      equally well with both techniques. 3D ultrasound should be complemented by
      careful gynecological exploration in order to identify any alterations in the
      cervix.

PMID- 20052668
TI  - Involvement of integrins alpha(3)beta(1) and alpha(5)beta(1) and glycoprotein IIb
      in megakaryocyte-induced osteoblast proliferation.
AB  - As the prevalence of osteoporosis is expected to increase over the next few
      decades, the development of novel therapeutic strategies to combat this disorder
      becomes clinically imperative. These efforts draw extensively from an expanding
      body of knowledge pertaining to the physiologic mechanisms of skeletal
      homeostasis. To this body of knowledge, we contribute that cells of hematopoietic
      lineage may play a crucial role in balancing osteoblastic bone formation against
      osteoclastic resorption. Specifically, our laboratory has previously demonstrated
      that megakaryocytes (MKs) can induce osteoblast (OB) proliferation in vitro, but
      do so only when direct cell-to-cell contact is permitted. To further investigate
      the nature of this interaction, we have effectively neutralized several adhesion
      molecules known to function in the analogous interaction of MKs with another cell
      type of mesenchymal origin-the fibroblast (FB). Our findings implicate the
      involvement of fibronectin/RGD-binding integrins including alpha3beta1 (VLA-3)
      and alpha5beta1 (VLA-5) as well as glycoprotein (gp) IIb (CD41), all of which are
      known to be expressed on MK membranes. Furthermore, we demonstrate that
      interleukin (IL)-3 can enhance MK-induced OB activation in vitro, as demonstrated
      in the MK-FB model system. Taken together, these results suggest that although
      their physiologic and clinical implications are very different, these two models
      of hematopoietic-mesenchymal cell activation are mechanistically analogous in
      several ways.

PMID- 20052669
TI  - Bifidobacteria inhibit the inflammatory response induced by gliadins in
      intestinal epithelial cells via modifications of toxic peptide generation during
      digestion.
AB  - Celiac disease (CD) is a chronic enteropathy triggered by intake of gliadin, the
      toxic component of gluten. This study aims at evaluating the capacity of
      different Bifidobacterium strains to counteract the inflammatory effects of
      gliadin-derived peptides in intestinal epithelial (Caco-2) cells. A commercial
      extract of several gliadin (Gld) types (alpha, beta, gamma, [symbol: see text] )
      was subjected to in vitro gastrointestinal digestion (pepsin at pH 3, pancreatin
      bile at pH 6), inoculated or not with cell suspensions (10(8) colony forming
      units/ml) of either B. animalis IATA-A2, B. longum IATA-ES1, or B. bifidum IATA
      ES2, in a bicameral system. The generated gliadin-derived peptides were
      identified by reverse phase-HPLC-ESI-MS/MS. Caco-2 cell cultures were exposed to
      the different gliadin peptide digestions (0.25 mg protein/ml), and the mRNA
      expression of nuclear factor kappa-B (NF-kappaB), tumor necrosis factor alpha
      (TNF-alpha), and chemokine CXCR3 receptor were analyzed by semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) in stimulated cells. The
      production of the pro-inflammatory markers NF-kappaB p50, TNF-alpha, and IL-1beta
      (interleukine 1beta) by Caco-2 cells was also determined by ELISA. The peptides
      from gliadin digestions inoculated with bifidobacteria did not exhibit the toxic
      amino acid sequences identified in those noninoculated (alpha/beta-Gld [158-164]
      and alpha/beta-Gld [122-141]). The RT-PCR analysis evidenced a down-regulation in
      mRNA expression of pro-inflammatory biomarkers. Consistent with these results the
      production of NF-kappaB, TNF-alpha, and IL-1beta was reduced (18.2-22.4%, 28.0
      64.8%, and abolished, respectively) in cell cultures exposed to gliadin
      digestions inoculated with bifidobacteria. Therefore, bifidobacteria change the
      gliadin-derived peptide pattern and, thereby, attenuate their pro-inflammatory
      effects on Caco-2 cells.

PMID- 20052670
TI  - Immature and mature megakaryocytes enhance osteoblast proliferation and inhibit
      osteoclast formation.
AB  - Recent data suggest that megakaryocytes (MKs) play a role in skeletal
      homeostasis. In vitro and in vivo data show that MKs stimulate osteoblast (OB)
      proliferation and inhibit osteoclast (OC) formation, thus favoring net bone
      deposition. There are several mouse models with dysregulated megakaryopoiesis and
      resultant high bone mass phenotypes. One such model that our group has
      extensively studied is GATA-1 deficient mice. GATA-1 is a transcription factor
      required for normal megakaryopoiesis, and mice deficient in GATA-1 have increases
      in immature MK number and a striking increase in bone mass. While the increased
      bone mass could simply be a result of increased MK number, here we take a more in
      depth look at the MKs of these mice to see if there is a unique factor inherent
      to GATA-1 deficient MKs that favors increased bone deposition. We show that
      increased MK number does correspond with increased OB proliferation and decreased
      OC formation that stage of maturation does not alter the effect of MKs on bone
      cell lineages beyond the megakaryoblast stage, and that GATA-1 deficient MKs
      survive longer than wild-type controls. So while increased MK number in GATA-1
      deficient mice likely contributes to the high bone mass phenotype, we propose
      that the increased longevity of this lineage also plays a role. Since GATA-1
      deficient MKs live longer they are able to exert both more proliferative
      influence on OBs and more inhibitory influence on OCs.

PMID- 20052671
TI  - Ursolic acid overcomes Bcl-2-mediated resistance to apoptosis in prostate cancer
      cells involving activation of JNK-induced Bcl-2 phosphorylation and degradation.
AB  - Androgen-independent prostate cancers express high levels of Bcl-2, and this over
      expression of Bcl-2 protects prostate cancer cells from undergoing apoptosis.
      Ursolic acid (UA) has demonstrated an anti-proliferative effect in various tumor
      types. The aim of this study is to evaluate the difference between UA-induced
      apoptosis in androgen-dependent prostate cancer cell line LNCaP cells and
      androgen-independent prostate cancer cell line LNCaP-AI cells and to reveal the
      molecular mechanisms underlying the apoptosis. We found that UA treatment in
      vitro can effectively induce apoptosis in LNCaP and LNCaP-AI cells. UA can
      overcome Bcl-2-mediated resistance to apoptosis in LNCaP-AI cells. Intrinsic
      apoptotic pathways can be triggered by UA treatment because c-Jun N-terminal
      kinase (JNK) is activated and subsequently provokes Bcl-2 phosphorylation and
      degradation, inducing activation of caspase-9. Although further evaluation is
      clearly needed, the present results suggest the potential utility of UA as a
      novel therapeutic agent in advanced prostate cancer.

PMID- 20052672
TI  - Differentiation of human umbilical cord Wharton's jelly-derived mesenchymal stem
      cells into germ-like cells in vitro.
AB  - Recent studies have demonstrated that mesenchymal stem cells could differentiate
      into germ cells under appropriate conditions. We sought to determine whether
      human umbilical cord Wharton's jelly-derived mesenchymal stem cells (HUMSCs)
      could form germ cells in vitro. HUMSCs were induced to differentiate into germ
      cells in all-trans retinoic acid, testosterone and testicular-cell-conditioned
      medium prepared from newborn male mouse testes. HUMSCs formed "tadpole-like"
      cells after induction with different reagents and showed both mRNA and protein
      expression of germ-cell-specific markers Oct4 (POUF5), Ckit, CD49(f) (alpha6),
      Stella (DDPA3), and Vasa (DDX4). Our results may provide a new route for
      reproductive therapy involving HUMSCs and a novel in vitro model to investigate
      the molecular mechanisms that regulate the development of the mammalian germ
      lineage.

PMID- 20052673
TI  - Down-regulation of Notch-1 and Jagged-1 inhibits prostate cancer cell growth,
      migration and invasion, and induces apoptosis via inactivation of Akt, mTOR, and
      NF-kappaB signaling pathways.
AB  - Notch signaling is involved in a variety of cellular processes, such as cell fate
      specification, differentiation, proliferation, and survival. Notch-1 over
      expression has been reported in prostate cancer metastases. Likewise, Notch
      ligand Jagged-1 was found to be over-expressed in metastatic prostate cancer
      compared to localized prostate cancer or benign prostatic tissues, suggesting the
      biological significance of Notch signaling in prostate cancer progression.
      However, the mechanistic role of Notch signaling and the consequence of its down
      regulation in prostate cancer have not been fully elucidated. Using multiple
      cellular and molecular approaches such as MTT assay, apoptosis assay, gene
      transfection, real-time RT-PCR, Western blotting, migration, invasion assay and
      ELISA, we found that down-regulation of Notch-1 or Jagged-1 was mechanistically
      associated with inhibition of cell growth, migration, invasion and induction of
      apoptosis in prostate cancer cells, which was mediated via inactivation of Akt,
      mTOR, and NF-kappaB signaling. Consistent with these results, we found that the
      down-regulation of Notch-1 or Jagged-1 led to decreased expression and the
      activity of NF-kappaB downstream genes such as MMP-9, VEGF, and uPA, contributing
      to the inhibition of cell migration and invasion. Taken together, we conclude
      that the down-regulation of Notch-1 or Jagged-1 mediated inhibition of cell
      growth, migration and invasion, and the induction of apoptosis was in part due to
      inactivation of Akt, mTOR, and NF-kappaB signaling pathways. Our results further
      suggest that inactivation of Notch signaling pathways by innovative strategies
      could be a potential targeted approach for the treatment of metastatic prostate
      cancer.

PMID- 20052674
TI  - TAp63 is a transcriptional target of NF-kappaB.
AB  - The p53 homologue p63 encodes multiple protein isoforms either with (TA) or
      without (DeltaN) the N-terminal transactivation domain. Accumulating evidence
      indicates that TAp63 plays an important role in various biological processes,
      including cell proliferation, differentiation, and apoptosis. However, how TAp63
      is regulated remains largely unclear. In this study, we demonstrate that NF
      kappaB induces TAp63 gene expression. The responsible elements for NF-kappaB
      mediated TAp63 induction are located within the region from -784 to -296 bp in
      the TAp63 promoter, which contains two NF-kappaB binding sites. Ectopic
      expression of RelA stimulates TAp63 promoter-driven reporter activity and
      increases endogenous TAp63 mRNA levels. Inhibition of NF-kappaB by IkappaBalpha
      super-repressor or with a chemical inhibitor leads to down regulation of TAp63
      mRNA expression and activity. In addition, mutations in the critical NF-kappaB
      binding sites significantly abolish the effects of NF-kappaB on TAp63. Activation
      of NF-kappaB by TNFalpha enhances p50/RelA binding to the NF-kappaB binding
      sites. Furthermore, we show that an Sp1 site adjacent to the NF-kappaB sites
      plays a role in NF-kappaB-mediated upregulation of TAp63. Taken together, these
      data reveal that TAp63 is a transcriptional target of NF-kappaB, which may play a
      role in cell proliferation, differentiation and survival upon NF-kappaB
      activation by various stimuli.

PMID- 20052675
TI  - RB gene family: genome-wide ChIP approaches could open undiscovered roads.
AB  - Many in vitro and reporter assays have helped to clarify how transcription
      factors regulate gene transcription. Today, it is important to decode the map of
      all transcription factor binding sites in the genome context. Chromatin
      immunoprecipitation followed by genome-wide analyses have tremendously opened new
      ways to analyze the mechanisms of action of DNA binding factors, cofactors and
      epigenetic modifications. It is now possible to correlate these regulatory
      mechanisms with genomic features such as the promoter, enhancer, silencer,
      intragenic, and intergenic DNA sequences. These approaches help to clarify the
      complex rules that govern many biological processes. In this review we discuss
      the genome-wide approaches applied to the retinoblastoma gene family (RBF), the
      central player of cell cycle control. There are also new, possible directions
      that are suggested within the review that can be followed to further explore the
      role of each pRb members in the transcriptional networks of the cell.

PMID- 20052676
TI  - Protein kinase C epsilon-dependent extracellular signal-regulated kinase 5
      phosphorylation and nuclear translocation involved in cardiomyocyte hypertrophy
      with angiotensin II stimulation.
AB  - Angiotensin II (Ang II) plays a critical role in hypertrophy of cardiomyocytes;
      however, the molecular mechanism, especially the signaling cascades, in
      cardiomyocytes remains unclear. In the present study, we examined the mechanism
      of Ang II in hypertrophy of cardiomyocytes. Ang II rapidly stimulated
      phosphorylation of protein kinase C epsilon (PKCepsilon) in a time- and dose
      dependent manner via Ang II receptor-1 (AT(1)). Furthermore, Ang II-induced
      extracellular signal-regulated kinase 5 (ERK5) phosphorylation and translocation
      was mediated through a signal pathway that involves AT(1) and PKCepsilon, which
      resulted in transcriptional activation of myocyte enhancer factor-2C (MEF2C) and
      hypertrophy. Consequently, inhibiting PKCepsilon or ERK5 by small interfering RNA
      (siRNA) significantly attenuated Ang II-induced MEF2C activation and hypertrophy
      of rat cardiomyocytes. These data provide evidence that PKCepsilon-dependent ERK5
      phosphorylation and nucleocytoplasmic traffic mediates Ang II-induced MEF2C
      activation and cardiomyocyte hypertrophy. PKCepsilon and ERK5 may be potential
      targets in the treatment of pathological vascular hypertrophy associated with the
      enhanced renin-angiotensin system.

PMID- 20052677
TI  - Combination therapy with sulfonylureas and metformin and the prevention of death
      in type 2 diabetes: a nested case-control study.
AB  - PURPOSE: To determine whether combination of sulfonylureas and metformin
      increases the risk of death from any cause in patients with type 2 diabetes.
      METHODS: A nested case-control study was conducted within a population-based
      cohort from the UK General Practice Research Database (GPRD). The cohort included
      patients over the age of 40 who were prescribed a first oral hypoglycaemic agent
      between 1 January 1988 and 30 June 2008. Cases included all patients who deceased
      during follow-up. Up to 10 controls were matched to each case on year of birth,
      date of cohort entry (+/-1 year) and duration of follow-up. Conditional logistic
      regression was used to estimate rate ratios (RRs) of death from any cause
      associated with the use of combination of sulfonylureas and metformin, relative
      to sulfonylurea monotherapy. RESULTS: The cohort comprised 84 231 users of oral
      hypoglycaemic agents, of whom 14 996 died from any cause during a mean of 4.3
      years of follow-up (mortality rate 4.1 per 100 per year). Patients currently
      exposed to a combination of sulfonylureas and metformin were at a decreased risk
      of death from any cause compared to patients exposed to sulfonylurea monotherapy
      (adjusted RR: 0.77, 95%CI: 0.70, 0.85). Similar results were obtained for
      patients currently exposed to metformin monotherapy (adjusted RR: 0.70, 95%CI:
      0.64, 0.75) when compared to sulfonylurea monotherapy. Patients had to be exposed
      to the combination therapy for at least 4 months prior to index date to
      experience a lower risk of mortality compared to sulfonylurea monotherapy.
      CONCLUSIONS: The combination of sulfonylureas and metformin does not increase the
      risk of death. In contrast, it may moderately reduce this risk compared to
      sulfonylurea monotherapy.

PMID- 20052678
TI  - The function of GluR1 and GluR2 in cerebellar and hippocampal LTP and LTD is
      regulated by interplay of phosphorylation and O-GlcNAc modification.
AB  - Long-term potentiation (LTP) and long-term depression (LTD) are the current
      models of synaptic plasticity and widely believed to explain how different kinds
      of memory are stored in different brain regions. Induction of LTP and LTD in
      different regions of brain undoubtedly involve trafficking of AMPA receptor to
      and from synapses. Hippocampal LTP involves phosphorylation of GluR1 subunit of
      AMPA receptor and its delivery to synapse whereas; LTD is the result of
      dephosphorylation and endocytosis of GluR1 containing AMPA receptor. Conversely
      the cerebellar LTD is maintained by the phosphorylation of GluR2 which promotes
      receptor endocytosis while dephosphorylation of GluR2 triggers receptor
      expression at the cell surface and results in LTP. The interplay of
      phosphorylation and O-GlcNAc modification is known as functional switch in many
      neuronal proteins. In this study it is hypothesized that a same phenomenon
      underlies as LTD and LTP switching, by predicting the potential of different
      Ser/Thr residues for phosphorylation, O-GlcNAc modification and their possible
      interplay. We suggest the involvement of O-GlcNAc modification of
      dephosphorylated GluR1 in maintaining the hippocampal LTD and that of
      dephosphorylated GluR2 in cerebral LTP.

PMID- 20052680
TI  - Crystal structure of Streptococcus pneumoniae Sp1610, a putative tRNA
      methyltransferase, in complex with S-adenosyl-L-methionine.
AB  - Streptococcus pneumoniae Sp1610, a Class-I fold S-adenosylmethionine (AdoMet)
      dependent methyltransferase, is a member of the COG2384 family in the Clusters of
      Orthologous Groups database, which catalyzes the methylation of N(1)-adenosine at
      position 22 of bacterial tRNA. We determined the crystal structure of Sp1610 in
      the ligand-free and the AdoMet-bound forms at resolutions of 2.0 and 3.0 A,
      respectively. The protein is organized into two structural domains: the N
      terminal catalytic domain with a Class I AdoMet-dependent methyltransferase fold,
      and the C-terminal substrate recognition domain with a novel fold of four alpha
      helices. Observations of the electrostatic potential surface revealed that the
      concave surface located near the AdoMet binding pocket was predominantly
      positively charged, and thus this was predicted to be an RNA binding area. Based
      on the results of sequence alignment and structural analysis, the putative
      catalytic residues responsible for substrate recognition are also proposed.

PMID- 20052679
TI  - Comparison of human solute carriers.
AB  - Solute carriers are eukaryotic membrane proteins that control the uptake and
      efflux of solutes, including essential cellular compounds, environmental toxins,
      and therapeutic drugs. Solute carriers can share similar structural features
      despite weak sequence similarities. Identification of sequence relationships
      among solute carriers is needed to enhance our ability to model individual
      carriers and to elucidate the molecular mechanisms of their substrate specificity
      and transport. Here, we describe a comprehensive comparison of solute carriers.
      We link the proteins using sensitive profile-profile alignments and two
      classification approaches, including similarity networks. The clusters are
      analyzed in view of substrate type, transport mode, organism conservation, and
      tissue specificity. Solute carrier families with similar substrates generally
      cluster together, despite exhibiting relatively weak sequence similarities. In
      contrast, some families cluster together with no apparent reason, revealing
      unexplored relationships. We demonstrate computationally and experimentally the
      functional overlap between representative members of these families. Finally, we
      identify four putative solute carriers in the human genome. The solute carriers
      include a biomedically important group of membrane proteins that is diverse in
      sequence and structure. The proposed classification of solute carriers, combined
      with experiment, reveals new relationships among the individual families and
      identifies new solute carriers. The classification scheme will inform future
      attempts directed at modeling the structures of the solute carriers, a
      prerequisite for describing the substrate specificities of the individual
      families.

PMID- 20052681
TI  - Genetic encoding of non-natural amino acids in Drosophila melanogaster Schneider
      2 cells.
AB  - Insect cells are useful for the high-yield production of recombinant proteins
      including chemokines and membrane proteins. In this study, we developed an insect
      cell-based system for incorporating non-natural amino acids into proteins at
      specific sites. Three types of promoter systems were constructed, and their
      efficiencies were compared for the expression of the prokaryotic amber suppressor
      tRNA(Tyr) in Drosophila melanogaster Schneider 2 cells. When paired with a
      variant of Escherichia coli tyrosyl-tRNA synthetase specific for 3-iodo-L
      tyrosine, the suppressor tRNA transcribed from the U6 promoter most efficiently
      incorporated the amino acid into proteins in the cells. The transient and stable
      introductions of these prokaryotic molecules into the insect cells were then
      compared in terms of the yield of proteins containing non-natural amino acids,
      and the "transient" method generated a sevenfold higher yield. By this method, 4
      azido-L-phenylalanine was incorporated into human interleukin-8 at a specific
      site. The yield of the azido-containing IL-8 was 1 microg/1 mL cell culture, and
      the recombinant protein was successfully labeled with a fluorescent probe by the
      Staudinger-Bertozzi reaction.

PMID- 20052682
TI  - Approaches to efficient production of recombinant angiogenesis inhibitor rhVEGI
      192 and characterization of its structure and antiangiogenic function.
AB  - Methods to prepare pure, bioactive recombinant human vascular endothelial growth
      inhibitor (rhVEGI), a potent inhibitor of angiogenesis potentially applicable in
      antiangiogenic cancer therapy, are in urgent demand for preclinical investigation
      as well as future clinical trials of the protein. Here, we report expression and
      purification of rhVEGI-192, a recombinant VEGI isoform, comparatively using host
      strains BL21 (DE3) pLysS and Origami B (DE3) with IPTG-induction and
      autoinduction techniques. Our study identified that a combined use of Origami B
      (DE3) strain and autoinduction expression system gave rise to a high yield of
      purified rhVEGI-192 at 105.38 mg/L culture by immobilized-metal affinity
      chromatography on Ni-NTA column. The antiangiogenic activity was effectively
      restored after the insoluble fractions being dissolved in 8M urea and
      subsequently subjected to a gradient-dialysis refolding process. Functional tests
      demonstrated that the purified rhVEGI-192 potently inhibited endothelial growth,
      induced endothelial apoptosis and suppressed neovascularization in chicken
      chorioallantoic membrane, indicating that the developed method allows preparation
      of rhVEGI-192 with high yield, solubility, and bioactivity. Most importantly, our
      study also demonstrates that VEGI-192 is capable of forming polymeric structure,
      which is possibly required for its antiangiogenic activity.

PMID- 20052683
TI  - Conserved tertiary couplings stabilize elements in the PDZ fold, leading to
      characteristic patterns of domain conformational flexibility.
AB  - Single-domain allostery has been postulated to occur through intramolecular
      pathways of signaling within a protein structure. We had previously investigated
      these pathways by introducing a local thermal perturbation and analyzed the
      anisotropic propagation of structural changes throughout the protein. Here, we
      develop an improved approach, the Rotamerically Induced Perturbation (RIP), that
      identifies strong couplings between residues by analyzing the pathways of heat
      flow resulting from thermal excitation of rotameric rotations at individual
      residues. To explore the nature of these couplings, we calculate the complete
      coupling maps of 5 different PDZ domains. Although the PDZ domain is a well
      conserved structural fold that serves as a scaffold in many protein-protein
      complexes, different PDZ domains display unique patterns of conformational
      flexibility in response to ligand binding: some show a significant shift in a set
      of alpha-helices, while others do not. Analysis of the coupling maps suggests a
      simple relationship between the computed couplings and observed conformational
      flexibility. In domains where the alpha-helices are rigid, we find couplings of
      the alpha-helices to the body of the protein, whereas in domains having ligand
      responsive alpha-helices, no couplings are found. This leads to a model where the
      alpha-helices are intrinsically dynamic but can be damped if sidechains interact
      at key tertiary contacts. These tertiary contacts correlate to high covariation
      contacts as identified by the statistical coupling analysis method. As these
      dynamic modules are exploited by various allosteric mechanisms, these tertiary
      contacts have been conserved by evolution.

PMID- 20052684
TI  - Six minute walk distance or stair negotiation? Choice of activity assessment
      following total knee replacement.
AB  - BACKGROUND AND PURPOSE: Physiotherapists evaluating changing functional
      performance in patients who have undergone total knee replacement (TKR) will
      often measure a number of gait-related activities, including six-minute walk
      distance (6MWD) and the capacity to ascend and descend stairs. In this report, we
      investigated the correlations between the 6MWD and stair ascent and descent power
      in a group of patients who had participated in a clinical trial at 2, 8 and 26
      weeks post-TKR to establish whether there is redundancy in conducting all three
      tests. METHODS: Retrospective analysis of data from a clinical trial was used.
      One hundred patients (57 female, 43 male) were tested on their 6MWD and power
      generated and absorbed during stair ascent and descent, respectively. Linear
      regression modelling was used to determine correlations between pairs of
      variables at the three measurement intervals. RESULTS: There were consistent
      relationships between each pair of variables at each measurement interval (r >
      0.70; p < 0.001) and also a consistency in the regressions between measurements.
      CONCLUSION: The findings indicate that there is no particular benefit to the
      therapist in measuring more than one of the three variables if the purpose of the
      measurement is to serve as an indicator of ambulatory functional status for
      routine clinical assessment.

PMID- 20052685
TI  - A megalin polymorphism associated with promoter activity and Alzheimer's disease
      risk.
AB  - Elevated cerebral levels of amyloid beta-protein (Abeta) occur in Alzheimer's
      disease (AD), yet only a few patients show evidence of increased Abeta
      production. This observation suggests that many, perhaps most, cases of AD are
      caused by faulty clearance of Abeta. Megalin, which plays an important role in
      mediating Abeta clearance, is an attractive candidate gene for genetic
      association with AD. To investigate this hypothesis, we analyzed the megalin gene
      in a population of 2,183 subjects. Genetic analysis indicated that the rs3755166
      (G/A) polymorphism located in the megalin promoter associated with risk for AD,
      dependently of apolipoprotein E genotype. The rs3755166 AA genotype frequency was
      significantly greater in AD patients than in control subjects. Furthermore, the
      luciferase reporter assay indicated that the rs3755166 A variant has 20% less
      transcriptional activity than the rs3755166 G variant. This study provides strong
      evidence that this megalin polymorphism confers a greater risk for AD, and
      supports a biological role for megalin in the neurodegenerative processes
      involved in AD.

PMID- 20052686
TI  - Functional variants of TSPAN8 are associated with bipolar disorder and
      schizophrenia.
AB  - Tetraspanins affect protein trafficking and are known to influence a wide variety
      of physiologic processes. Recently, single nucleotide polymorphisms (SNPs) of the
      tetraspanin gene TSPAN8 were found among the best ranked markers of genome wide
      association studies on bipolar disorder (BPD) (rs1705236) and type-2 diabetes,
      but functional consequences remained largely unknown. In the present study, we
      examined 13 tagging SNPs covering the TSPAN8 gene, the intronic TSPAN8 SNP
      rs1705236 as well as two non-synonymous (ns) SNPs in schizophrenia (SCZ) and BPD
      samples. In our analysis setting, we were not able to replicate the association
      of rs1705236 with BPD, nor did we find an association with SCZ. In the TSPAN8
      upstream transcriptional control region however, we found rs4500567 to be
      associated with BPD. In contrast, in SCZ the nsSNP rs3763978 was associated with
      disease. The significance of both associations withstood conservative Bonferroni
      correction. In an attempt to link the polymorphisms to functional consequences,
      we performed an allele-specific in silico mapping of transcription factor binding
      sites around rs4500567 and predicted the tolerance of the Gly73Ala exchange
      caused by rs3763978. The results argue for a differential promoter activity
      specific for the variant associated with BPD, but impaired protein functionality
      in SCZ. This suggests that TSPAN8 contributes to both diseases, yet with
      different underlying mechanisms: regulatory versus structural. Similar phenomena
      might also occur in other risk genes for both BPD and SCZ, providing a molecular
      basis for the genetic overlap of both entities.

PMID- 20052687
TI  - Sharing space: can ethnoprimatology contribute to the survival of nonhuman
      primates in human-dominated globalized landscapes?
AB  - The emerging discipline of ethnoprimatology has at its core the construct that
      humans and nonhuman primates share a planet, an evolutionary history and a
      "primate perspective" on the world; more simply stated ethnoprimatolgy suggests
      that humans have perspectives on nonhuman primates which can contribute
      positively to the primates' enduring survival in our increasingly human-dominated
      landscapes. Here, I explore whether humans can or do contribute positively to the
      conservation of nonhuman primates, or whether humanity's impact on, as well as
      our perceptions of, primates are generally negative. I examine primate-human
      interactions at the intersection of agriculture with natural habitats as
      exemplified in several long-term studies, and explore the conservation
      consequences of these interactions. These interactions are then placed into an
      ecological-economic perspective assessing the prospects for the survival of
      primates in a context where humans share their subsistence space and resources
      with primates.

PMID- 20052688
TI  - Simultaneous analysis of serotonin transporter, tryptophan hydroxylase 1 and 2
      gene expression in the ventral prefrontal cortex of suicide victims.
AB  - Serotonergic signaling abnormalities have been implicated in suicide. Tryptophan
      hydroxylase (TPH), the rate limiting enzyme of serotonin biosynthesis and the
      serotonin transporter (SLC6A4), involved in the reuptake of serotonin from the
      synaptic gap, play major role in serotonergic signaling. In this study, we aimed
      to compare the levels of expression of these serotonin-related genes between
      suicide completers and controls and to identify genetic loci involved in their
      regulation. SLC6A4, TPH1, and TPH2 mRNA levels were measured in the ventral
      prefrontal cortex (VPFC) of 39 suicide completers and 40 matched controls. To
      identify the molecular basis of gene expression variation, we performed
      association studies between cis-acting polymorphisms and SLC6A4, TPH1, and TPH2
      transcript levels. Finally, association analyses were carried out between suicide
      and TPH2 cis-single nucleotide polymorphisms (SNPs) in cohorts of 154 suicide
      completers and 289 control subjects. Whereas SLC6A4 and TPH1 mRNA expression
      levels did not differ between suicides and controls, TPH2 levels were found
      significantly increased (P = 0.003) in suicide completers. We observed that SNP
      rs10748185 located in the promoter region of TPH2 significantly affect levels of
      TPH2 mRNA expression. However, we did not find positive association between this
      eQTL (rs10748185) and suicide. Here, we report the simultaneous analysis of the
      expression of three serotonin-related genes in the VPFC of suicide victims and
      controls. This study showed that TPH2 expression levels were increased in the
      VPFC of suicide victims. Although, we identified a genetic variant that explains
      variance in TPH2 expression, we did not find evidence associating this cis
      regulatory SNP with suicidal behavior.

PMID- 20052689
TI  - Failure to confirm association between PIK4CA and psychosis in 22q11.2 deletion
      syndrome.

PMID- 20052690
TI  - Has 'lifetime prevalence' reached the end of its life? An examination of the
      concept.
AB  - Many cross-sectional surveys in psychiatric epidemiology report estimates of
      lifetime prevalence, and the results consistently show a declining trend with age
      for such disorders as depression and anxiety. In a closed cohort with no
      mortality, lifetime prevalence should increase or remain constant with age. For
      mortality to account for declining lifetime prevalence, mortality rates in those
      with a disorder must exceed those without a disorder by a sufficient extent that
      more cases would be removed from the prevalence pool than are added by new cases,
      and this is unlikely to occur across most of the age range. We argue that the
      decline in lifetime prevalence with age cannot be explained by period or cohort
      effects or be due to a survivor effect, and are likely due to a variety of other
      factors, such as study design, forgetting, or reframing. Further, because
      lifetime prevalence is insensitive to changes in treatment effectiveness or
      demand for services, it is a parameter that should be dropped from the lexicon of
      psychiatric epidemiology.

PMID- 20052691
TI  - Sex differences in the vocal repertoire of adult red-capped mangabeys (Cercocebus
      torquatus): A multi-level acoustic analysis.
AB  - Sex differences in the vocal behavior of nonhuman primates can take various
      forms: sex-specific call types, differential production of shared call types, or
      sex discrepancy in phonation. Also, a growing literature is evidencing that
      systematically analyzing the vocal repertoires of primates at the call level
      might lead to underestimating their communicative abilities. Here, we present an
      extensive multi-level analysis of the still unknown vocal repertoire of adult red
      capped mangabeys (Cercocebus torquatus), with a special emphasis on sex
      differences. We collected recordings from seven adult males and seven adult
      females housed in captivity. We present a structurally-based classification of
      mangabey calls that we cross-validated by an analysis of the associated contexts
      of emission. We found 12 sound units (including six sex-specific) that were
      concatenated to form eight call types (including four sex-specific), which were
      produced either singularly or in sequences composed of one ("repetition") or
      several ("combination") call types. We extracted organizational principles that
      ruled call composition and calling patterns. This revealed a high degree of
      potentially meaningful variability in terms of semantics and syntax. Male-female
      discrepancy in terms of phonation could be related to morphological dimorphism
      and would enable listeners to behave appropriately according to the sex of the
      caller. Sex differences in repertoire size, structural gradation, and call usage
      could reflect specificities of male-female social roles. We discuss the
      pertinence of these sex differences according to social system and habitat
      quality.

PMID- 20052692
TI  - Heritability estimates for cognitive factors and brain white matter integrity as
      markers of schizophrenia.
AB  - Recent genetics research focusing on schizophrenia has led to candidate cognitive
      and neuroimaging variables as intermediate phenotypes or "endophenotype" markers
      for the illness. Among other stringent criteria, to be an endophenotype, a marker
      must demonstrate heritability. In an effort to explore the validity of a
      selection of cognitive and neuroimaging endophenotypes, the present study was
      designed to determine estimates of their heritability. One hundred fourteen
      subjects, including 27 with schizophrenia and 39 unaffected relatives from 23
      multiplex schizophrenia families, participated in a comprehensive
      neuropsychological test battery and structural brain imaging with diffusion
      tensor imaging (DTI). Variables were selected if they previously have been
      demonstrated to show differences between people with schizophrenia and normal
      controls. Significant evidence of heritability was confirmed for overall
      cognitive function ("g"), as well as expressive and receptive language, verbal
      and visual memory, processing speed and cognitive inhibition. In addition,
      significant heritability estimates were determined for specific regions in the
      frontal, central, parietal, and occipital areas. These results suggest that the
      variables chosen may be useful endophenotypes for genetic and early detection
      studies, although further work with larger cohorts should be conducted to show
      that deficits in these functions and structures also segregate with schizophrenia
      within families and thus fully satisfy the definition of an endophenotype. In
      addition, other cognitive and neuroimaging variables that were not studied here
      may be candidates for schizophrenia endophenotypes.

PMID- 20052693
TI  - Great apes track hidden objects after changes in the objects' position and in
      subject's orientation.
AB  - Eight chimpanzees (Pan troglodytes), five bonobos (Pan paniscus), five gorillas
      (Gorilla gorilla), and seven orangutans (Pongo pygmaeus) were presented with two
      invisible object displacement tasks. In full view of the subject, a food item was
      hidden under one of three opaque cups resting on a platform and, after an
      experimental manipulation, the subject was allowed to select one of the cups. In
      the rotation task, the platform was rotated 180 degrees while the subject
      remained stationary. In the translocation task, the platform remained stationary
      while the subject walked to the opposite side from where she saw the reward being
      hidden. The final position of the food relative to the subject was equivalent in
      both tasks. Single displacement trials consisted of only one manipulation, either
      a rotation or a translocation, whereas double displacement trials consisted of
      both a rotation and a translocation. We also included no displacement trials in
      which no displacements took place. No displacement trials were easier than single
      displacements which, in turn, were easier than double displacements. Unlike
      earlier studies with children, there was no difference in performance between
      rotation and translocation displacements. Overall, apes performed above chance in
      all conditions, but chimpanzees outperformed the other species. This study
      reinforces the notion that the great apes use an allocentric spatial coding.

PMID- 20052694
TI  - Testing the developmental distinctiveness of male proactive and reactive
      aggression with a nested longitudinal experimental intervention.
AB  - An experimental preventive intervention nested into a longitudinal study was used
      to test the developmental distinctiveness of proactive and reactive aggression.
      The randomized multimodal preventive intervention targeted a subsample of boys
      rated disruptive by their teachers. These boys were initially part of a sample of
      895 boys, followed from kindergarten to 17 years of age. Semiparametric analyses
      of developmental trajectories for self-reported proactive and reactive aggression
      (between 13 and 17 years of age) indicated three trajectories for each type of
      aggression that varied in size and shape (Low, Moderate, and High Peaking).
      Intent-to-treat comparisons between the boys in the prevention group and the
      control group confirmed that the preventive intervention between 7 and 9 years of
      age, which included parenting skills and social skills training, could impact the
      development of reactive more than proactive aggression. The intervention effect
      identified in reactive aggression was related to a reduction in self-reported
      coercive parenting. The importance of these results for the distinction between
      subtypes of aggressive behaviors and the value of longitudinal-experimental
      studies from early childhood onward is discussed.

PMID- 20052695
TI  - An FTIR study of monkey green- and red-sensitive visual pigments.

PMID- 20052696
TI  - Methane activation and catalytic ethylene formation on free Au(2) (+).

PMID- 20052697
TI  - A simple lithium(I) salt with a microporous structure and its gas sorption
      properties.

PMID- 20052698
TI  - Single molecules as optical nanoprobes for soft and complex matter.
AB  - The optical signals of single molecules provide information about structure and
      dynamics of their nanoscale environment, free from space and time averaging.
      These new data are particularly useful whenever complex structures or dynamics
      are present, as in polymers or in porous oxides, but also in many other classes
      of materials, where heterogeneity is less obvious. We review the main uses of
      single molecules in studies of condensed matter at nanometer scales, especially
      in the fields of soft matter and materials science. We discuss several examples,
      including the orientation distribution of molecules in crystals, rotational
      diffusion in glass-forming molecular liquids, polymer studies with probes and
      labeled chains, porous and heterogeneous oxide materials, blinking of single
      molecules and nanocrystals, and the potential of surface-enhanced Raman
      scattering for local chemical analysis. All these examples show that static and
      dynamic heterogeneities and the spread of molecular parameters are much larger
      than previously imagined.

PMID- 20052699
TI  - Metal coordination mediated reversible conversion between linear and cross-linked
      supramolecular polymers.

PMID- 20052700
TI  - Total synthesis of (+)-isatisine A.

PMID- 20052701
TI  - An electrochemical and photophysical study of a covalently linked inorganic
      organic dyad.
AB  - A molecular donor-acceptor dyad comprising a hexarhenium cluster core,
      [Re(6)(mu(3)-Se)(8)](2+), and a fullerene moiety which are covalently linked
      through a pyridine ligand was synthesized and fully characterized. The
      electrochemical and photophysical properties are reported. The detailed study
      includes cyclic voltammetry, steady-state absorption and fluorescence
      spectroscopy, radiation chemistry and transient absorption spectroscopy. A light
      induced electron transfer between the inorganic cluster moiety and the fullerene
      can be excluded. However, a light-induced energy transfer from the rhenium
      cluster to the fullerene is proposed.

PMID- 20052702
TI  - A self-assembly route for double bilayer lipid membrane formation.

PMID- 20052703
TI  - Recent advances in multicatalyst promoted asymmetric tandem reactions.
AB  - Multicatalyst promoted asymmetric tandem reactions have emerged as a powerful
      strategy to improve the synthetic efficiency. It enables the synthesis of complex
      molecules with high selectivity from simple starting materials in an almost
      biomimetic-like way. The use of multiple catalyst systems can enlarge the
      substrate and reaction scope for the reaction design, improve the reactivity, and
      benefit the control of selectivity. In this Focus Review, the current achievement
      of this promising field is discussed, including the advantages and difficulties
      of this research, and the strategies applied to address these problems.

PMID- 20052704
TI  - Poly(ionic liquid)-mediated hybridization of single-walled carbon nanotubes and
      conducting polymers.

PMID- 20052705
TI  - Alternatives to organoboron reagents in rhodium-catalyzed conjugate additions.
AB  - The rhodium-catalyzed conjugate addition of organoboron reagents to alkene
      acceptors has emerged as an important methodology in organic synthesis. The
      process results in the formation of new carbon-carbon bonds, and in principle,
      can create new stereocenters at both the alpha and beta carbon atoms of the
      acceptor. Other organometallics are known to participate in the key
      transmetalation to rhodium and are becoming more established in stereoselective
      synthesis (notably arylzinc reagents). This Focus Review will describe recent
      developments in the use of alternative organometallic donors to organoboron
      reagents in rhodium-catalyzed conjugate addition reactions and their growing
      applications in synthesis.

PMID- 20052706
TI  - An unexpected stereochemical course of dihydroimidazolium ylide cycloadditions.

PMID- 20052707
TI  - Aqueous cationic polyurethane dispersions from vegetable oils.

PMID- 20052708
TI  - HER2- and EGFR-specific affiprobes: novel recombinant optical probes for cell
      imaging.
AB  - The human epidermal growth factor receptors, EGFR and HER2, are members of the
      EGFR family of cell-surface receptors/tyrosine kinases. EGFR- and HER2-positive
      cancers represent a more aggressive disease with greater likelihood of
      recurrence, poorer prognosis, and decreased survival rate, compared to EGFR- or
      HER2-negative cancers. The details of HER2 proto-oncogenic functions are not
      deeply understood, partially because of a restricted availability of tools for
      EGFR and HER2 detection (A. Sorkin and L. K. Goh, Exp. Cell Res. 2009, 315, 683
      696). We have created photostable and relatively simple-to-produce imaging probes
      for in vitro staining of EGFR and HER2. These new reagents, called affiprobes,
      consist of a targeting moiety, a HER2- or EGFR-specific Affibody molecule, and a
      fluorescent moiety, mCherry (red) or EGFP (green). Our flow cytometry and
      confocal microscopy experiments demonstrated high specificity and
      signal/background ratio of affiprobes. Affiprobes are able to stain both live
      cells and frozen tumor xenograph sections. This type of optical probe can easily
      be extended for targeting other cell-surface antigens/ receptors.

PMID- 20052711
TI  - Structures of human Bruton's tyrosine kinase in active and inactive conformations
      suggest a mechanism of activation for TEC family kinases.
AB  - Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, plays a
      crucial role in B-cell maturation and mast cell activation. Although the
      structures of the unphosphorylated mouse BTK kinase domain and the
      unphosphorylated and phosphorylated kinase domains of human ITK are known,
      understanding the kinase selectivity profiles of BTK inhibitors has been hampered
      by the lack of availability of a high resolution, ligand-bound BTK structure.
      Here, we report the crystal structures of the human BTK kinase domain bound to
      either Dasatinib (BMS-354825) at 1.9 A resolution or to 4-amino-5-(4
      phenoxyphenyl)-7H-pyrrolospyrimidin- 7-yl-cyclopentane at 1.6 A resolution. This
      data provides information relevant to the development of small molecule
      inhibitors targeting BTK and the TEC family of nonreceptor tyrosine kinases.
      Analysis of the structural differences between the TEC and Src families of
      kinases near the Trp-Glu-Ile motif in the N-terminal region of the kinase domain
      suggests a mechanism of regulation of the TEC family members.

PMID- 20052709
TI  - 5-Stabilized phosphatidylinositol 3,4,5-trisphosphate analogues bind Grp1 PH,
      inhibit phosphoinositide phosphatases, and block neutrophil migration.
AB  - Metabolically stabilized analogues of PtdIns(3,4,5)P3 have shown long-lived
      agonist activity for cellular events and selective inhibition of lipid
      phosphatase activity. We describe an efficient asymmetric synthesis of two 5
      phosphatase-resistant analogues of PtdIns(3,4,5)P3, the 5-methylene phosphonate
      (MP) and 5-phosphorothioate (PT). Furthermore, we illustrate the biochemical and
      biological activities of five stabilized PtdIns(3,4,5)P3 analogues in four
      contexts. First, the relative binding affinities of the 3-MP, 3-PT, 5-MP, 5-PT,
      and 3,4,5-PT3 analogues to the Grp1 PH domain are shown, as determined by NMR
      spectroscopy. Second, the enzymology of the five analogues is explored, showing
      the relative efficiency of inhibition of SHIP1, SHIP2, and phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN), as well as the greatly reduced ability
      of these phosphatases to process these analogues as substrates as compared to
      PtdIns(3,4,5)P3. Third, exogenously delivered analogues severely impair
      complement factor C5a-mediated polarization and migration of murine neutrophils.
      Finally, the new analogues show long-lived agonist activity in mimicking insulin
      action in sodium transport in A6 cells.

PMID- 20052712
TI  - N1S3: a revised staging system for head and neck cutaneous squamous cell
      carcinoma with lymph node metastases: results of 2 Australian Cancer Centers.
AB  - BACKGROUND: A staging system was designed for metastatic cutaneous squamous cell
      carcinoma (SCC) that would incorporate the parotid as a regional level and
      facilitate a better prognostic discrimination between subgroups. METHODS: A
      retrospective review of clinical and pathological information of patients treated
      for metastatic cutaneous SCC to the parotid and/or neck was conducted. Potential
      prognostic factors were analyzed using univariate and multivariate analyses. A
      staging system was elaborated and externally validated. RESULTS: Two hundred
      fifteen patients were included. All patients had surgery as their primary
      treatment; 148 had parotidectomy with neck dissection, 50 parotidectomy alone,
      and 18 neck dissection alone. One hundred seventy-five patients received
      postoperative radiotherapy. On univariate analysis, the number of involved lymph
      nodes (P < .001), maximal size (P = .01), and extracapsular spread (P = .003)
      were found to be significant predictors of survival. On Cox regression, the
      number of involved lymph nodes as single or multiple (P = .006) was significant.
      The N1S3 staging system incorporates involved lymph nodes from parotid and neck
      (single or multiple) and the size (< or >3 cm). This system demonstrates
      significant predictive capacity for locoregional control (P < .001), disease
      specific survival (P<.0001), and overall survival (P<.0001). N1S3 was tested on a
      different cohort of 250 patients, and the results confirmed those obtained from
      our primary analyses. CONCLUSIONS: The N1S3 system stages patients according to
      the number of involved lymph nodes and size, and incorporates parotid as 1 of the
      regional levels. These 2 predictors are easily applied on both clinical and
      pathological data.

PMID- 20052713
TI  - Primary central nervous system post-transplantation lymphoproliferative disorder:
      an International Primary Central Nervous System Lymphoma Collaborative Group
      Report.
AB  - BACKGROUND: Primary central nervous system (CNS) post-transplantation
      lymphoproliferative disorder (PCNS-PTLD) is a rare complication of solid organ
      transplantation. The objectives of this study were to define the clinical,
      radiologic, and pathologic features of this disease and to explore the impact of
      treatment on patient outcomes. METHODS: The authors reviewed the databases of
      participating institutions of the International Primary CNS Lymphoma
      Collaborative Group for cases of PCNS-PTLD. Thirty-four patients who had
      pathologically confirmed PCNS-PTLD without evidence of systemic PTLD were
      investigated retrospectively. RESULTS: The median time from transplantation to
      diagnosis of PCNS-PTLD was 4.4 years. Disease usually was multifocal and involved
      any location of the brain but was most common in the cerebral hemispheres,
      usually in the subcortical white matter or basal ganglia. Radiographically, all
      lesions enhanced either homogenously or in a ring-enhancing pattern. Cerebral
      biopsy was required to establish diagnosis in most patients. Most patients had
      monomorphic, Epstein-Barr virus (EBV)-positive disease of B-cell origin. Response
      rates were high regardless of treatment type, and the median survival was 47
      months. Age was the only factor predictive of survival. CONCLUSIONS: The current
      study demonstrated that PCNS-PTLD is typically an EBV-induced B-cell lymphoma
      that is responsive to treatment with favorable survival in many patients. An
      aggressive approach to tissue confirmation of diagnosis and treatment with
      chemotherapy or radiotherapy should be strongly considered.

PMID- 20052714
TI  - The effects of paclitaxel, dose density, and trastuzumab on treatment-related
      amenorrhea in premenopausal women with breast cancer.
AB  - BACKGROUND: Little information is available regarding the effects of new adjuvant
      treatment regimens on menstrual functioning in premenopausal women with early
      breast cancer. METHODS: The authors conducted a retrospective review of data from
      premenopausal women who received treatment for early breast cancer to evaluate
      the rates of amenorrhea in follow-up. The women who were included received
      treatment with either doxorubicin and cyclophosphamide (AC) or combined AC and
      paclitaxel (T) (AC-T) given either every 3 weeks, or as a dose-dense (DD)
      regimen, or as AC followed by weekly T with trastuzumab or followed by
      trastuzumab (AC-T+trastuzumab). A multivariate logistic regression analysis was
      conducted to evaluate amenorrhea during follow-up. RESULTS: Of 431 patients who
      were eligible for analysis, the average age at diagnosis was 13 years (range, 25
      55 years), 61% of women received AC only, and 39% received AC-T. Of the 39% who
      received AC-T, 49% of women received DD therapy, 14% received AC-T+trastuzumab,
      and 71% of all patients received tamoxifen (TAM). The median follow-up was 33
      months (range, 6-114 months). After adjusting for age, weight, gravidity, parity,
      age at menarche, smoking, alcohol use, TAM use, type and regimen of chemotherapy,
      and use of trastuzumab, the likelihood of remaining amenorrheic was not
      statistically different in patients who received AC-T versus AC (odds ratio [OR],
      1.59; 95% confidence interval [CI], 0.8-3.2), DD treatment versus treatment every
      3 weeks (OR, 0.56; 95% CI, 0.25-1.3), or AC-T + trastuzumab (OR, 0.6; 95% CI,
      0.22-1.61). Amenorrhea was associated significantly with TAM use and age at
      diagnosis. CONCLUSIONS: Recent advances in the adjuvant treatment of early breast
      cancer do not appear to have increased the risk of amenorrhea in premenopausal
      women.

PMID- 20052715
TI  - Antiangiogenesis agents in the treatment of soft tissue sarcomas.
AB  - Soft tissue sarcomas (STSs) are a heterogeneous group of malignancies that
      includes >50 different subtypes, each with unique clinical and pathologic
      qualities. In general, there is a 50% cure rate, and most cures are achieved with
      complete surgical resection with or without radiation therapy. The results from
      chemotherapeutic agents for unresectable or metastatic disease have been
      disappointing with minimal long-term benefit. New targeted and novel agents are
      needed to improve response and survival. Tumor angiogenesis has been an intense
      focus in cancer therapy over the past decade. Several of numerous
      antiangiogenesis agents have been developed, and many already have been approved
      for the treatment of both solid and liquid tumors. Certain STSs are highly
      vascular tumors that often demonstrate angiogenesis markers. The objective of
      this review was to evaluate these angiogenesis markers in defining the role of
      angiogenesis in the treatment of patients with STS. In addition, the authors
      conducted an in-depth review of the results from using key antiangiogenesis
      agents in the treatment of STS.

PMID- 20052717
TI  - Clinical characteristics and outcomes for a modern series of primary gliosarcoma
      patients.
AB  - BACKGROUND: Primary gliosarcoma (PGS) is a rare central nervous system tumor with
      limited experience reported in the literature. In the current study, the authors
      present a modern series of confirmed PGS cases treated in the era of magnetic
      resonance imaging (MRI), after the accepted glioblastoma management of resection,
      radiation, and temozolomide. METHODS: Using a retrospective review, patients with
      confirmed PGS were identified (1996-2008). Cases were determined to be PGS by
      central pathology review using the 2007 World Health Organization criteria.
      Extensive chart review was performed to gather clinical and pathologic data on
      these cases. RESULTS: All but 1 patient had undergone a preoperative MRI, with 1
      patient receiving a computed tomography scan due to a cardiac pacemaker. A total
      of 10 patients received radiotherapy with concurrent and adjuvant temozolomide
      chemotherapy, and 8 patients received radiotherapy alone or in combination with
      other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment
      could not be confirmed. The overall median survival was 13.9 months (range, 2.2
      22.9 months). Patients with gliosarcomas resembling meningioma were found to have
      a significantly prolonged median survival compared with patients harboring
      gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P =
      .011). However, no difference in survival was noted between patients who received
      concurrent radiotherapy and temozolomide compared with those who did not (10.4
      months vs 13.9 months; P = .946). CONCLUSIONS: The results of the current study
      support previous hypotheses that there are 2 distinct types of PGS. The type
      mimicking the appearance of a meningioma appears to carry a significantly more
      favorable prognosis, most likely due to an increased chance at achieving
      macroscopic total resection.

PMID- 20052718
TI  - Early (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify
      a subset of patients with estrogen receptor-positive breast cancer who will not
      respond optimally to preoperative chemotherapy.
AB  - BACKGROUND: A pathologic complete response (pCR) and minimal residual disease
      (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced
      breast cancer (BC) correlates with a good prognosis. METHODS: Patients who
      received from 6 to 8 cycles of PCT for BC were monitored by (18)F-2-fluoro-2
      deoxy-D-glucose positron emission tomography ((18)F-FDG-PET), and the maximal
      standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles,
      after 4 cycles, and at the end of PCT. SUVmax percentage changes (Delta-SUV) were
      compared with the pathologic response rate. Patients who had a pCR or pMRD in the
      tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were
      defined as having obtained an optimal pathologic response (pR), whereas all the
      other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of
      34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had
      pMRD). After the second cycle, the Delta-SUV threshold with optimal negative
      predictive value to predict a pR was 50%. Twenty-six patients (76%) had a Delta
      SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR.
      Conversely, all 8 patients who had a Delta-SUV < or =50% had a pNR. All 8 of
      those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early
      evaluation of metabolic response by (18)F-FDG-PET during PCT was able to identify
      30% of patients, all with estrogen receptor-positive tumors, who would not obtain
      pR after completion of chemotherapy program.

PMID- 20052720
TI  - Marital quality and survivorship: slowed recovery for breast cancer patients in
      distressed relationships: marital distress and the health of breast cancer
      patients.

PMID- 20052721
TI  - A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of
      paclitaxel for the treatment of metastatic breast cancer.
AB  - BACKGROUND: This study was performed to compare efficacy and toxicity profiles of
      paclitaxel using 3-hour versus 96-hour infusion schedules. METHODS: Patients with
      metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel
      starting at a dose of 250 mg/m(2) intravenously (iv) over 3 hours every 21 days
      or paclitaxel starting at a dose of 140 mg/m(2) iv over 96 hours every 21 days.
      Stratification variables included number of prior chemotherapy regimens and
      previous response to anthracyclines. Response was assessed every 2 cycles using
      bidimensional measurements. Patients were allowed to cross over at disease
      progression or therapy intolerance. RESULTS: A total of 214 patients received
      therapy (107 patients per arm). Response rates were similar: 23.4% in the 3-hour
      arm and 29.9% in the 96-hour arm (P = .28). The median duration of response (8.9
      months vs 5.7 months; P = .75) and progression-free survival (5.0 months vs 3.8
      months; P = .17) slightly favored the 96-hour arm. Overall survival was slightly
      longer in the 3-hour arm (14.2 months vs 12.7 months; P = .57). One patient who
      crossed over to the 96-hour arm (N = 18) developed a partial response; no
      response was noted with crossover to the 3-hour arm (N = 10). Myalgia/arthralgia
      and neuropathy were more frequent in the 3-hour arm, whereas mucositis,
      neutropenic fever/infection, and diarrhea were more common in the 96-hour arm.
      CONCLUSIONS: Paclitaxel given by 3-hour or 96-hour infusion was active in MBC.
      The 96-hour paclitaxel regimen did not significantly improve response or time to
      disease progression, was more cumbersome to administer, and was associated with
      greater myelosuppression (but less neuropathy and myalgia) compared with the 3
      hour schedule.

PMID- 20052722
TI  - Nonsynonymous single nucleotide polymorphisms in DNA damage repair pathways and
      lung cancer risk.
AB  - BACKGROUND: Several reports have revealed the association between single
      nucleotide polymorphisms (SNPs) and the development of cancer. Although many SNPs
      have been investigated, they were tested individually. In this study,
      nonsynonymous SNPs present in DNA damage response genes were comprehensively
      analyzed for lung cancer susceptibility. METHODS: The authors selected 37
      nonsynonymous SNPs in 23 genes involved in DNA damage repair pathways. Fifty lung
      adenocarcinoma patients resected at their institution between 2002 and 2005 and
      50 individuals without any known history of cancer were recruited for a case
      control study. RESULTS: Three variants (XRCC1 194Trp homozygotes, POLdelta1
      119His homozygotes, and RAD9 239Arg heterozygotes) tended to coassociate with
      lung cancer risk. The authors analyzed and calculated whether the association
      between combinations of these 3 SNPs significantly affected the risk of lung
      cancer. Compared with carriers of either XRCC1 194Trp homozygote or RAD9 239Arg
      heterozygote variants, noncarriers were at a significantly decreased risk for
      lung cancer (odds ratio [OR], 0.282; confidence interval [CI], 0.089-0.893). The
      same results were found for the combination of POLdelta1 119His homozygotes and
      RAD9 239Arg heterozygotes (OR, 0.277; CI, 0.077-0.993). Moreover, compared with
      carriers that had at least 1 of the 3 variants, noncarriers showed a more
      significant decrease in risk (OR, 0.263; CI, 0.090-0.767). CONCLUSIONS: Analysis
      of the presence of XRCC1 194Trp homozygote, POLdelta1 119His homozygote, and RAD9
      239Arg heterozygote variants revealed that their coassociation leads to a
      significant risk for the development of lung adenocarcinoma. Inclusive analyses
      of different SNPs were important in this cancer risk study.

PMID- 20052724
TI  - Pelvic fractures after radiotherapy for cervical cancer: implications for
      survivors.
AB  - BACKGROUND: The incidence of pelvic fractures and associated risk factors was
      determined in women treated with curative-intent radiotherapy for cervical
      cancer. METHODS: The records of 516 women treated with curative-intent
      radiotherapy for cervical cancer between 2001 and 2006 at the University of Texas
      M. D. Anderson Cancer Center were reviewed. Among these, 300 patients had at
      least 1 post-treatment computed tomography scan or magnetic resonance imaging
      study available for review, and they comprised our study population. All imaging
      studies were re-reviewed by a single radiologist to evaluate for fractures.
      RESULTS: Pelvic fractures were noted in 29 of 300 patients (9.7%). Fracture sites
      included sacrum (n = 24; 83%), sacrum and pubis (n = 3; 10%), iliac crest (n = 1;
      3%), and sacrum and acetabulum (n = 1; 3%). Thirteen patients (45%) were
      symptomatic, with pain being the most common presenting symptom. The median time
      from the completion of radiotherapy to the detection of fractures on imaging
      studies was 14.1 months (range, 2.1-63.1 months), with 38% of patients diagnosed
      within 1 year and 83% diagnosed within 2 years of completing therapy. The median
      age of the patients at diagnosis was higher in the women who developed a fracture
      compared with the women who did not (56.5 years vs 46.7 years; P = .04). A higher
      number of women with a fracture were postmenopausal (62% vs 37%; P = .03). The
      median body mass index was lower in the women who had a fracture (26.0 kg/m2 vs
      28.0 kg/m2; P = .03). CONCLUSIONS: Pelvic fractures were detected in a
      substantial proportion of women after radiotherapy for cervical cancer. Bone
      mineral density screening and pharmacologic intervention should be considered in
      these women.

PMID- 20052723
TI  - Impact of smoking on patients with stage III colon cancer: results from Cancer
      and Leukemia Group B 89803.
AB  - BACKGROUND: Cigarette smoking has been shown to increase the risk of developing
      colorectal cancer, particularly smoking early in life. Little is known about the
      impact of tobacco use on colon cancer recurrence among colon cancer survivors.
      METHODS: The authors prospectively collected lifetime smoking history from stage
      III colon cancer patients enrolled in a phase 3 trial via self-report
      questionnaires during and 6 months after completion of adjuvant chemotherapy.
      Smoking status was defined as never, current, or past. Lifetime pack-years were
      defined as number of lifetime packs of cigarettes. Patients were followed for
      recurrence or death. RESULTS: Data on smoking history were captured on 1045
      patients with stage III colon cancer receiving adjuvant therapy (46% never
      smokers; 44% past; 10% current). The adjusted hazard ratio (HR) for disease-free
      survival (DFS) was 0.99 (95% confidence interval [CI], 0.70-1.41), 1.17 (95% CI
      0.89-1.55), and 1.22 (95% CI 0.92-1.61) for lifetime pack-years 0-10, 10-20, and
      20+, respectively, compared with never smoking (P = .16). In a preplanned
      exploratory analysis of smoking intensity early in life, the adjusted HR for 12+
      pack-years before age 30 years for DFS was 1.37 (95% CI, 1.02-1.84) compared with
      never smoking (P = .04). The adjusted HR for DFS was 1.18 (95% CI, 0.92-1.50) for
      past smokers and 1.10 (95% CI, 0.73-1.64) for current smokers, compared with
      never smokers. CONCLUSIONS: Total tobacco usage early in life may be an
      important, independent prognostic factor of cancer recurrences and mortality in
      patients with stage III colon cancer.

PMID- 20052725
TI  - Ethnic and racial differences in patients with Ewing sarcoma.
AB  - BACKGROUND: Ewing sarcoma (ES) was a malignant tumor of bone or soft tissue. One
      of the few risk factors for developing ES is race, with a higher incidence noted
      in populations of European rather than African or Asian ancestry. The goal of the
      current study was to evaluate racial and ethnic differences in presentation and
      overall survival (OS) among patients diagnosed with ES before age 40 years.
      METHODS: Data from the Surveillance, Epidemiology, and End Results database
      identified 1715 patients aged <40 years who were diagnosed with ES between 1973
      and 2005. Racial and ethnic group differences were compared using chi-square
      tests. OS was estimated by Kaplan-Meier analysis and compared using log-rank
      tests and Cox models. RESULTS: Black patients had significantly more soft-tissue
      tumors compared with white non-Hispanic patients (P <.0001). Asian and white
      Hispanic patients were found to have an intermediate frequency of soft-tissue
      tumors that also differed from white non-Hispanic patients (P <.0001). White
      Hispanic patients presented with a higher proportion of larger tumors compared
      with white non-Hispanic patients (P = .042). Black patients tended to be older
      than white non-Hispanic patients (P = .012). Sex, frequency of pelvic tumors, and
      metastatic status did not appear to differ by ethnicity or race. OS was found to
      differ according to race and ethnicity. Even after controlling for known
      confounders, OS was significantly worse for black, Asian, and white Hispanic
      patients compared with white non-Hispanic patients (P = .0031, P = .0182, and P =
      .0051, respectively). CONCLUSIONS: Ethnic and racial differences in
      characteristics and outcomes of patients with ES do exist. Understanding the
      etiology of these differences will require further study.

PMID- 20052726
TI  - Dissecting racial disparities in the treatment of patients with locoregional
      pancreatic cancer: a 2-step process.
AB  - BACKGROUND: Previous studies have demonstrated that black patients with
      pancreatic cancer are less likely to undergo resection and have worse overall
      survival compared with white patients. The objective of this study was to
      determine whether these disparities occur at the point of surgical evaluation or
      after evaluation has taken place. METHODS: The authors used the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare linked data (1992-2002) to compare
      black patients and white patients with locoregional pancreatic cancer in
      univariate models. Logistic regression was used to determine the effect of race
      on surgical evaluation and on surgical resection after evaluation. Cox
      proportional hazards models were used to identify which factors influenced 2-year
      survival. RESULTS: Nine percent of 3777 patients were black. Blacks were
      substantially less likely than whites to undergo evaluation by a surgeon (odds
      ratio, 0.57; 95% confidence interval, 0.42-0.77) when the model was adjusted for
      demographics, tumor characteristics, surgical evaluation, socioeconomic status,
      and year of diagnosis. Patients who were younger and who had fewer comorbidities,
      abdominal imaging, and a primary care physician were more likely to undergo
      surgical evaluation. Once they were seen by a surgeon, blacks still were less
      likely than whites to undergo resection (odds ratio, 0.64; 95% confidence
      interval, 0.49-0.84). Although black patients had decreased survival in an
      unadjusted model, race no longer was significant after accounting for resection.
      CONCLUSIONS: Twenty-nine percent of black patients with potentially resectable
      pancreatic cancers never received surgical evaluation. Without surgical
      evaluation, patients cannot make an informed decision and will not be offered
      resection. Attaining higher rates of surgical evaluation in black patients would
      be the first step to eliminating the observed disparity in the resection rate.

PMID- 20052728
TI  - Perils of quinolone exposure in cancer patients: breakthrough bacteremia with
      multidrug-resistant organisms.
AB  - BACKGROUND: The objective of this study was to determine the effect of antibiotic
      use (including prophylaxis) on the emergence of multidrug-resistant (MDR)
      breakthrough bacteremia in cancer patients. METHODS: In this retrospective study,
      the authors identified all bacteremia episodes from July 2005 to December 2006 at
      their tertiary cancer center and compared the bacteria types and antimicrobial
      resistance in isolates from patients who had received antimicrobial agents as
      therapy or prophylaxis (breakthrough infections) with those from patients who had
      not received antimicrobial agents (nonbreakthrough bacteremia). RESULTS:
      Breakthrough bacteremia was more likely to be associated with MDR Escherichia
      coli (P = .002), MDR Pseudomonas aeruginosa (P = .02), and vancomycin-resistant
      enterococci (P = .01). Multivariate analysis revealed that breakthrough
      bacteremia was associated with hematologic malignancies and neutropenia (odds
      ratios, 9.9 and 3.0, respectively). Fluoroquinolone use was associated
      significantly with the emergence of methicillin-resistant Staphylococcus aureus
      (P = .04), MDR E. coli (P < .001), and MDR P. aeruginosa (P = .05). A strong
      association was observed between fluoroquinolone use and breakthrough bacteremia
      in multivariate analysis (odds ratio, 22; P < .001). Patients who had received
      vancomycin were more likely to have vancomycin-resistant enterococci bloodstream
      isolates than patients who had not received antibacterial agents (P < .001).
      CONCLUSIONS: Breakthrough infections were more common in neutropenic patients and
      in patients who had hematologic malignancies. The isolation of MDR organisms was
      associated strongly with the use of fluoroquinolones. The current findings
      demonstrated the importance of using a comprehensive approach to the prevention
      of MDR bacterial infections, including the initiation of antibiotic stewardship
      programs.

PMID- 20052727
TI  - Ultra-early predictive assay for treatment failure using functional magnetic
      resonance imaging and clinical prognostic parameters in cervical cancer.
AB  - BACKGROUND: The authors prospectively evaluated magnetic resonance imaging (MRI)
      parameters quantifying heterogeneous perfusion pattern and residual tumor volume
      early during treatment in cervical cancer, and compared their predictive power
      for primary tumor recurrence and cancer death with the standard clinical
      prognostic factors. A novel approach of augmenting the predictive power of
      clinical prognostic factors with MRI parameters was assessed. METHODS: Sixty-two
      cervical cancer patients underwent dynamic contrast-enhanced (DCE) MRI before and
      during early radiation/chemotherapy (2-2.5 weeks into treatment). Heterogeneous
      tumor perfusion was analyzed by signal intensity (SI) of each tumor voxel. Poorly
      perfused tumor regions were quantified as lower 10th percentile of SI (SI[10%]).
      DCE-MRI and 3-dimensional (3D) tumor volumetry MRI parameters were assessed as
      predictors of recurrence and cancer death (median follow-up, 4.1 years). Their
      discriminating capacity was compared with clinical prognostic factors (stage,
      lymph node status, histology) using sensitivity/specificity and Cox regression
      analysis. RESULTS: SI(10%) and 3D volume 2-2.5 weeks into therapy independently
      predicted disease recurrence (hazard ratio [HR], 2.6; 95% confidence interval
      [95% CI], 1.0-6.5 [P = .04] and HR, 1.9; 95% CI, 1.1-3.5 [P = .03], respectively)
      and death (HR, 1.9; 95% CI, 1.0-3.5 [P = .03] and HR, 1.9; 95% CI, 1.2-2.9 [P =
      .01], respectively), and were superior to clinical prognostic factors. The
      addition of MRI parameters to clinical prognostic factors increased sensitivity
      and specificity of clinical prognostic factors from 71% and 51%, respectively, to
      100% and 71%, respectively, for predicting recurrence, and from 79% and 54%,
      respectively, to 93% and 60%, respectively, for predicting death. CONCLUSIONS:
      MRI parameters reflecting heterogeneous tumor perfusion and subtle tumor volume
      change early during radiation/chemotherapy are independent and better predictors
      of tumor recurrence and death than clinical prognostic factors. The combination
      of clinical prognostic factors and MRI parameters further improves early
      prediction of treatment failure and may enable a window of opportunity to alter
      treatment strategy.

PMID- 20052729
TI  - Epstein-Barr virus latent membrane protein 1 mRNA is expressed in a significant
      proportion of patients with chronic lymphocytic leukemia.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with Richter
      transformation in patients with chronic lymphocytic leukemia (CLL). METHODS: A
      direct isothermal mRNA amplification method was developed for detection of EBV
      latent membrane protein 1 (LMP1) mRNA transcriptional activity in the peripheral
      blood of 135 chronic lymphocytic leukemia patients and 98 hematologically healthy
      control subjects. RESULTS: EBV LMP1 mRNA transcripts were found in 19 of 135
      (14%) of the CLL cases, but only 1% of the healthy controls (P < .0001). In
      contrast, 23 solid tumor patients tested negative for EBV LMP1 transcripts. In a
      later cohort of patients after hematopoietic stem cell transplantation, 4 of 7
      patients with Hodgkin lymphoma or Burkitt lymphoma had EBV LMP1 detected. In a
      preliminary analysis, outcome data were available for 88 of the 135 patients with
      CLL. EBV LMP1 mRNA positivity was associated with a significantly increased
      degree of histologically demonstrated bone marrow involvement by CLL (P = .003,
      Mann-Whitney U test). CONCLUSIONS: EBV LMP1 mRNA transcriptional activity was
      observed in a significant proportion of CLL patients. Transcription of the EBV
      LMP1, a late gene with known transforming potential in vitro, suggests that EBV
      activation plays a role in CLL disease progression. Thus, EBV LMP1 expression in
      CLL patients may be a factor involved in the genesis of refractory disease.

PMID- 20052730
TI  - Should extrapulmonary small cell cancer be managed like small cell lung cancer?
AB  - BACKGROUND: The aim of this study was to determine if extrapulmonary small cell
      carcinomas (EPSCC) should be managed using protocols similar to those for small
      cell lung cancer (SCLC). METHODS: Treatment strategies, survival, patterns of
      failure, and prognostic factors for patients with EPSCC were analyzed
      retrospectively at a large cancer center. SCLC was excluded by thoracic computed
      tomography (75%) or chest radiography (25%). RESULTS: Of 120 eligible patients,
      70% had limited disease (LD). Treatment modalities included chemotherapy (n = 82;
      68%), radiotherapy (RT) (n = 80; 67%), and surgery (n = 41, 34%). The median
      survival for patients with LD and extensive disease was 1.4 years and 0.7 years,
      respectively. Gynecologic (n = 31) and gastrointestinal (n = 28) were the most
      common primary tumor sites. Gynecologic and head and neck primary tumor sites had
      better 1-year survival than other sites (P = .019 and 0.005, respectively). Brain
      metastasis was the site of first distant failure in 4.1% of patients versus 35%
      for soft tissue metastases. The lifetime risk of brain metastasis was 13%.
      Definitive RT (P = .004), LD (P = .028), and prophylactic cranial irradiation
      (PCI) (P = .022) were found to be positive prognostic factors and weight loss (P
      < .001) was a negative prognostic factor on multivariate analysis. CONCLUSIONS:
      Patients with EPSCC usually experienced short survival, often with early distant
      metastasis. Although PCI was associated with improved overall survival, brain
      metastasis was less frequent than in patients with SCLC, and therefore the
      potential benefit of PCI was less than in patients with SCLC. Definitive
      chemoradiotherapy was associated with better outcomes and should be delivered
      whenever feasible.

PMID- 20052731
TI  - Predictors of timely follow-up after abnormal cancer screening among women
      seeking care at urban community health centers.
AB  - BACKGROUND: We sought to measure time and identify predictors of timely follow-up
      among a cohort of racially/ethnically diverse inner city women with breast and
      cervical cancer screening abnormalities. METHODS: Eligible women had an
      abnormality detected on a mammogram or Papanicolaou (Pap) test between January
      2004 and December 2005 in 1 of 6 community health centers in Boston,
      Massachusetts. Retrospective chart review allowed us to measure time to
      diagnostic resolution. We used Cox proportional hazards models to develop
      predictive models for timely resolution (defined as definitive diagnostic
      services completed within 180 days from index abnormality). RESULTS: Among 523
      women with mammography abnormalities and 474 women with Pap test abnormalities,
      >90% achieved diagnostic resolution within 12 months. Median time to resolution
      was longer for Pap test than for mammography abnormalities (85 vs 27 days). Site
      of care, rather than any sociodemographic characteristic of individuals,
      including race/ethnicity, was the only significant predictor of timely follow-up
      for both mammogram and Pap test abnormalities. CONCLUSIONS: Site-specific
      community-based interventions may be the most effective interventions to reduce
      cancer health disparities when addressing the needs of underserved populations.

PMID- 20052732
TI  - A trial of 3 interventions to promote colorectal cancer screening in African
      Americans.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death
      in the United States. CRC incidence and mortality rates are higher among blacks
      than among whites, and screening rates are lower in blacks than in whites. For
      the current study, the authors tested 3 interventions that were intended to
      increase the rate of CRC screening among African Americans. METHODS: The
      following interventions were chosen to address evidence gaps in the Centers for
      Disease Control and Prevention's Guide to Community Preventive Services: one-on
      one education, group education, and reducing out-of-pocket costs. Three hundred
      sixty-nine African-American men and women aged > or =50 years were enrolled in
      this randomized, controlled community intervention trial. The main outcome
      measures were postintervention increase in CRC knowledge and obtaining a
      screening test within 6 months. RESULTS: There was substantial attrition: Two
      hundred fifty-seven participants completed the intervention and were available
      for follow-up 3 months to 6 months later. Among completers, there were
      significant increases in knowledge in both educational cohorts but in neither of
      the other 2 cohorts. By the 6-month follow-up, 17.7% (11 of 62 participants) of
      the Control cohort reported having undergone screening compared with 33.9% (22 of
      65 participants) of the Group Education cohort (P = .039). Screening rate
      increases in the other 2 cohorts were not statistically significant. CONCLUSIONS:
      The current results indicated that group education could increase CRC cancer
      screening rates among African Americans. The screening rate of <35% in a group of
      individuals who participated in an educational program through multiple sessions
      over a period of several weeks indicated that there still are barriers to
      overcome.

PMID- 20052734
TI  - Mortality in men with localized prostate cancer treated with brachytherapy with
      or without neoadjuvant hormone therapy.
AB  - BACKGROUND: Discrepancies exist regarding the impact of neoadjuvant hormone
      therapy (NHT) on the risk of all-cause mortality (ACM) in men who receive
      brachytherapy for localized prostate cancer. Therefore, the objective of the
      current study was to examine the effect of NHT on the risk of ACM in men with
      prostate cancer who receive with brachytherapy. METHODS: The study cohort
      included 2474 men with localized prostate cancer who either received NHT (N =
      1083) or did not receive NHT (N = 1391) and brachytherapy without supplemental
      external beam radiation between 1991 and 2005 at centers within the 21st Century
      Oncology Consortium. All men had at least 2 years of follow-up. Low-risk,
      intermediate-risk, and high-risk disease was present in 65%, 23%, and 12% of men,
      respectively. A Cox regression multivariate analysis was used to evaluate the
      risk of ACM in men who received NHT compared with all others adjusting for age,
      prostate-specific antigen level, Gleason score, and tumor classification.
      RESULTS: After a median follow-up of 4.8 years (interquartile range, 3.3-7.5
      years) and adjusting for known prostate cancer prognostic factors and age,
      treatment with NHT was associated significantly with an increased risk of ACM
      (adjusted hazard ratio, 1.24; 95% confidence interval, 1.01-1.53; P = .04) in men
      aged > or =73 years. In men who were younger than the median age of 73 years,
      hormone therapy use was not significant (P = .34). CONCLUSIONS: Compared with men
      who were younger than the median age of 73 years, men aged > or =73 years with
      localized prostate cancer who received brachytherapy and NHT had an increased
      risk of ACM compared with men who did not receive NHT.

PMID- 20052733
TI  - p53 and MDM2 in renal cell carcinoma: biomarkers for disease progression and
      future therapeutic targets?
AB  - Renal cell carcinoma (RCC) is the most common type of kidney cancer and follows
      an unpredictable disease course. To improve prognostication, a better
      understanding of critical genes associated with disease progression is required.
      The objective of this review was to focus attention on 2 such genes, p53 and
      murine double minute 2 (MDM2), and to provide a comprehensive summary and
      critical analysis of the literature regarding these genes in RCC. Information was
      compiled by searching the PubMed database for articles that were published or e
      published up to April 1, 2009. Search terms included renal cancer, renal cell
      carcinoma, p53, and MDM2. Full articles and any supplementary data were examined;
      and, when appropriate, references were checked for additional material. All
      studies that described assessment of p53 and/or MDM2 in renal cancer were
      included. The authors concluded that increased p53 expression, but not p53
      mutation, is associated with reduced overall survival/more rapid disease
      progression in RCC. There also was evidence that MDM2 up-regulation is associated
      with decreased disease-specific survival. Two features of RCC stood out as
      unusual and will require further investigation. First, increased p53 expression
      is tightly linked with increased MDM2 expression; and, second, patients who have
      tumors that display increased p53 and MDM2 expression may have the poorest
      overall survival. Because there was no evidence to support the conclusion that
      p53 mutation is associated with poorer survival, it seemed clear that increased
      p53 expression in RCC occurs independent of mutation. Further investigation of
      the mechanisms leading to increased p53/MDM2 expression in RCC may lead to
      improved prognostication and to the identification of novel therapeutic
      interventions.

PMID- 20052735
TI  - Clinical impact of phosphorylated signal transducer and activator of
      transcription 3, epidermal growth factor receptor, p53, and vascular endothelial
      growth factor receptor 1 expression in resected adenocarcinoma of lung by using
      tissue microarray.
AB  - BACKGROUND: The signal transducer and activator of transcription 3 (STAT3) play a
      key role in the downstream pathway of the epidermal growth factor receptor (EGFR)
      in nonsmall cell lung cancer and promote cell proliferation, invasion, and
      angiogenesis. The clinical significance of phosphorylated STAT3 (pSTAT3), EGFR,
      p53, and vascular endothelial growth factor receptor 1 (VEGFR-1) expression in
      patients with completely resected lung adenocarcinoma was evaluated to determine
      the effects of pSTAT3 in tumor angiogenesis and proliferation. METHODS: The
      expressions of pSTAT3, EGFR, p53, and VEGFR-1 were evaluated by
      immunohistochemical staining of tissue microarrays from 162 samples of resected
      lung adenocarcinoma. RESULTS: The median age of the 162 patients was 62 years,
      the median disease-free survival was 41.7 months, and the median OS (OS) was 80.2
      months. Expression of pSTAT3, EGFR, p53, and VEGFR-1 was detected in 51.2%, 71%,
      35.2%, and 35.2% of the samples, respectively. pSTAT3 expression was correlated
      significantly with VEGFR-1 expression (P = .025). The coexpression of pSTAT3 and
      VEGFR-1 was correlated with increased lymph node involvement (P = .021) and a
      trend toward a short OS (P = .085). In multivariate analysis, the expression
      levels of p53 and VEGFR-1 were identified as independent prognostic factors that
      affected OS. CONCLUSIONS: The results of this study suggested that pSTAT3 and
      VEGFR-1 expression may play roles in the tumor progression and angiogenesis of
      lung adenocarcinoma. Further studies are needed, however, to uncover the detailed
      mechanisms that underlie the roles of these proteins in lung adenocarcinoma.

PMID- 20052736
TI  - Generational risks for cancers not related to tobacco, screening, or treatment in
      the United States.
AB  - BACKGROUND: To assess trends in cancer, the authors evaluated the risk of 1
      generation compared with that 25 years earlier (generational risk) for 3
      groupings of cancers: those related to tobacco; those that reflect advances in
      screening or treatment; and a residual category of all other cancers. METHODS: In
      individuals ages 20 years to 84 years, age-period-cohort models were used to
      summarize time trends in terms of generational risk and average annual percentage
      change for US cancer incidence (1975-2004) and mortality (1970-2004) rates
      associated with these 3 cancer groupings. RESULTS: Adult white men today
      developed 16% fewer tobacco-related cancers and had 21% fewer deaths because of
      those cancers than their fathers' generation, whereas adult white women
      experienced increases of 28% and 19%, respectively, relative to their mothers.
      The incidence of commonly screened cancers rose 74% in men and 10% in women,
      whereas mortality fell 25% in men and 31% in women. For cancers that have not
      been linked chiefly to tobacco or screening, the incidence was 34% and 23% higher
      in white men and white women, respectively, than in their parents' generation 25
      years earlier. Mortality in this residual category decreased 14% in men and 18%
      in women. Results among blacks were qualitatively similar to those among whites.
      CONCLUSIONS: Despite declining overall cancer death rates, adults are
      experiencing increased incidence of cancers that are not associated with tobacco
      or screening relative to their parents. Future research should examine whether
      similar patterns are exhibited in other modern nations and should identify
      population-wide avoidable risks that could account for unexplained increases in
      these residual cancers.

PMID- 20052737
TI  - Perfusion seeding of channeled elastomeric scaffolds with myocytes and
      endothelial cells for cardiac tissue engineering.
AB  - The requirements for engineering clinically sized cardiac constructs include
      medium perfusion (to maintain cell viability throughout the construct volume) and
      the protection of cardiac myocytes from hydrodynamic shear. To reconcile these
      conflicting requirements, we proposed the use of porous elastomeric scaffolds
      with an array of channels providing conduits for medium perfusion, and sized to
      provide efficient transport of oxygen to the cells, by a combination of
      convective flow and molecular diffusion over short distances between the
      channels. In this study, we investigate the conditions for perfusion seeding of
      channeled constructs with myocytes and endothelial cells without the gel carrier
      we previously used to lock the cells within the scaffold pores. We first
      established the flow parameters for perfusion seeding of porous elastomer
      scaffolds using the C2C12 myoblast line, and determined that a linear perfusion
      velocity of 1.0 mm/s resulted in seeding efficiency of 87% +/- 26% within 2
      hours. When applied to seeding of channeled scaffolds with neonatal rat cardiac
      myocytes, these conditions also resulted in high efficiency (77.2% +/- 23.7%) of
      cell seeding. Uniform spatial cell distributions were obtained when scaffolds
      were stacked on top of one another in perfusion cartridges, effectively closing
      off the channels during perfusion seeding. Perfusion seeding of single scaffolds
      resulted in preferential cell attachment at the channel surfaces, and was
      employed for seeding scaffolds with rat aortic endothelial cells. We thus propose
      that these techniques can be utilized to engineer thick and compact cardiac
      constructs with parallel channels lined with endothelial cells.

PMID- 20052738
TI  - Polyethylenimine/small interfering RNA-mediated knockdown of vascular endothelial
      growth factor in vivo exerts anti-tumor effects synergistically with Bevacizumab.
AB  - BACKGROUND: RNA interference is a powerful method for the knockdown of
      pathologically relevant genes. The in vivo delivery of siRNAs, preferably through
      systemic, nonviral administration, poses the major challenge in the therapeutic
      application of RNAi. Small interfering RNA (siRNA) complexation with
      polyethylenimines (PEI) may represent a promising strategy for siRNA-based
      therapies and, recently, the novel branched PEI F25-LMW has been introduced in
      vitro. Vascular endothelial growth factor (VEGF) is frequently overexpressed in
      tumors and promotes tumor growth, angiogenesis and metastasis and thus represents
      an attractive target gene in tumor therapy. METHODS: In subcutaneous tumor
      xenograft mouse models, we established the therapeutic efficacy and safety of PEI
      F25-LMW/siRNA-mediated knockdown of VEGF. In biodistribution and siRNA
      quantification studies, we optimized administration strategies and, employing
      chemically modified siRNAs, compared the anti-tumorigenic efficacies of: (i)
      PEI/siRNA-mediated VEGF targeting; (ii) treatment with the monoclonal anti-VEGF
      antibody Bevacizumab (Avastin); and (iii) a combination of both. RESULTS:
      Efficient siRNA delivery is observed upon systemic administration, with the
      biodistribution being dependent on the mode of injection. Toxicity studies reveal
      no hepatotoxicity, proinflammatory cytokine induction or other side-effects of
      PEI F25-LMW/siRNA complexes or polyethylenimine, and tumor analyses show
      efficient VEGF knockdown upon siRNA delivery, leading to reduced tumor cell
      proliferation and angiogenesis. The determination of anti-tumor effects reveals
      that, in pancreas carcinoma xenografts, single treatment with PEI/siRNA complexes
      or Bevacizumab is already highly efficacious, whereas, in prostate carcinoma,
      synergistic effects of both treatments are observed. CONCLUSIONS: PEI F25
      LMW/siRNA complexes, which can be stored frozen as opposed to many other
      carriers, represent an efficient, safe and promising avenue in anti-tumor
      therapy, and PEI/siRNA-mediated, therapeutic VEGF knockdown exerts anti-tumor
      effects.

PMID- 20052739
TI  - Modeling with a view to target identification in metabolic engineering: a
      critical evaluation of the available tools.
AB  - The state of the art tools for modeling metabolism, typically used in the domain
      of metabolic engineering, were reviewed. The tools considered are stoichiometric
      network analysis (elementary modes and extreme pathways), stoichiometric modeling
      (metabolic flux analysis, flux balance analysis, and carbon modeling),
      mechanistic and approximative modeling, cybernetic modeling, and multivariate
      statistics. In the context of metabolic engineering, one should be aware that the
      usefulness of these tools to optimize microbial metabolism for overproducing a
      target compound depends predominantly on the characteristic properties of that
      compound. Because of their shortcomings not all tools are suitable for every kind
      of optimization; issues like the dependence of the target compound's synthesis on
      severe (redox) constraints, the characteristics of its formation pathway, and the
      achievable/desired flux towards the target compound should play a role when
      choosing the optimization strategy.

PMID- 20052741
TI  - Improved in vivo gene transfer into tumor tissue by stabilization of
      pseudodendritic oligoethylenimine-based polyplexes.
AB  - BACKGROUND: HD O is a low molecular weight pseudodendrimer containing
      oligoethylenimine and degradable hexanediol diacrylate diesters. DNA polyplexes
      display encouraging gene transfer efficiency in vitro and in vivo but also a
      limited stability under physiological conditions. This limitation must be
      overcome for further development into more sophisticated formulations. METHODS:
      HD O polyplexes were laterally stabilized by crosslinking surface amines via
      bifunctional crosslinkers, bioreducible dithiobis(succimidyl propionate) (DSP) or
      the nonreducible analog disuccinimidyl suberate (DSS). Optionally, in a
      subsequent step, the targeting ligand transferrin (Tf) was attached to DSP-linked
      HD O polyplexes via Schiff base formation between HD O amino groups and Tf
      aldehyde groups, which were introduced into Tf by periodate oxidation of the
      glycosylation sites. RESULTS: Crosslinked DNA polyplexes showed an increased
      stability against exchange reaction by salt or heparin. Disulfide bond containing
      DSP-linked polyplexes were susceptible to reducing conditions. These polyplexes
      displayed the highest gene expression levels in vitro and in vivo (upon
      intratumoral application in mice), and these were significantly elevated and
      prolonged over standard or DSS-stabilized HD O formulations. DSP-stabilized HD O
      polyplexes with or without Tf coating were well-tolerated after intravenous
      application. High gene expression levels were found in tumor tissue, with
      negligible gene expression in any other organ. CONCLUSIONS: Lateral stabilization
      of HD O polyplexes with DSP crosslinker enhanced gene transfer efficacy and was
      essential for the incorporation of a ligand (Tf) into a stable particle
      formulation.

PMID- 20052742
TI  - The influence of semen-derived enhancer of virus infection on the efficiency of
      retroviral gene transfer.
AB  - BACKGROUND: An improvement of retroviral infection has been postulated using a
      naturally occurring fragment of the abundant semen marker prostatic acidic
      phosphatase. This peptide, termed semen-derived enhancer of virus infection
      (SEVI), promotes HIV attachment to the target cells. METHODS: In the present
      study, we examined whether SEVI would also enhance the infectivity of other
      viruses with different envelope proteins. We focused on retroviruses pseudotyped
      with envelopes that are commonly used for the genetic modification of cells, in
      particular, T cells and hematopoietic progenitor cells. Because the effect of
      SEVI is considered to be a result of its cationic properties, we compared SEVI
      with other cationic agents such as protamine sulfate and Polybrene. RESULTS: We
      found that SEVI increases the efficiency of gene transfer for lentiviral and
      gammaretroviral vector constructs pseudotyped with VSV-G, GALV, RD114 or foamy
      viral envelopes on hematopoietic and nonhematopoietic cell lines. On T cells, the
      transduction efficiency of GALV and RD114 pseudotyped vectors was significantly
      increased by SEVI. A significant increase of the gene transfer rate was also
      detected for foamy virally pseudotyped lentivirus on murine hematopoietic
      progenitor cells. No toxic effect of SEVI treatment was detected on any cell type
      tested, including human and murine hematopoietic stem/progenitor cells. When
      directly comparing the effect of SEVI with Polybrene or protamine sulfate, we
      show that the semen-derived protein is more efficient in increasing the gene
      transfer rate. CONCLUSIONS: SEVI is a promising agent for promoting and improving
      gene transfer and may also be useful for clinical gene therapy studies.

PMID- 20052743
TI  - Leukocytosis is a risk factor for recurrent arterial thrombosis in young patients
      with polycythemia vera and essential thrombocythemia.
AB  - There is evidence that leukocytosis is associated with an increased risk of first
      thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia
      (ET). Whether it is a risk factor for recurrent thrombosis too is currently
      unknown. In the frame of a multicenter retrospective cohort study, we recruited
      253 patients with PV (n = 133) or ET (n = 120), who were selected on the basis of
      a first arterial (70%) or venous major thrombosis (27.6%) or both (2.4%), and who
      were not receiving cytoreduction at the time of thrombosis. The probability of
      recurrent thrombosis associated with the leukocyte count recorded at the time of
      the first thrombosis was estimated by a receiver operating characteristic
      analysis and a multivariable Cox proportional hazards regression model.
      Thrombosis recurred in 78 patients (30.7%); multivariable analysis showed an
      independent risk of arterial recurrence (hazard ratio [HR] 2.16, 95% CI 1.12
      4.18) in patients with a leukocyte count that was >12.4 x 10(9)/L at the time of
      the first thrombotic episode. The prognostic role for leukocytosis was age
      related, as it was only significant in patients that were aged <60 years (HR for
      arterial recurrence 3.35, 95% CI 1.22-9.19).

PMID- 20052744
TI  - Acquired factor V inhibitor in a context of sepsis and disseminated intravascular
      coagulation.

PMID- 20052745
TI  - Resolution of cerebral artery stenosis in a child with sickle cell anemia treated
      with hydroxyurea.

PMID- 20052746
TI  - Severe thrombocytopenia and fibrinolysis mimicking disseminated intravascular
      coagulation after rituximab infusion.

PMID- 20052747
TI  - Deferasirox treatment may be associated with reversible renal Fanconi syndrome.

PMID- 20052748
TI  - Phase1/-2 study of Pomalidomide in myelofibrosis.

PMID- 20052749
TI  - Clinical impact of blood storage lesions.
AB  - Recent reports suggest that transfusion of old red blood cell (RBC) units (>2
      weeks) was associated with increased risks of postoperative complications and
      higher mortality rate caught public attention (Yap et al., Ann Thorac Surg 2008;
      86:554-559 and Koch et al., 2008; 358:1229-1239). This rekindled the decades old
      discussion regarding the impact of RBC aging and storage lesions in patient care.
      The objectives of this review are to provide readers with an overview of the
      process of banking RBC that may have an impact on its quality, the reported
      clinical impact of storage lesions, the consequences of transfusing new RBC units
      only to the nation's blood supply and potential solutions that may improve the
      feasibility of blood banks to issue new blood units only.

PMID- 20052750
TI  - Systemic AL amyloidosis with acquired factor X deficiency: A study of
      perioperative bleeding risk and treatment outcomes in 60 patients.
AB  - Systemic light-chain (AL) amyloidosis may be associated with acquired factor X
      (FX) deficiency and optimal management of this coagulopathy is unknown. We
      reviewed our experience with 60 patients with isolated FX deficiency (< or =50%)
      due to AL amyloidosis that underwent an invasive procedure between 1975 and 2007.
      They were classified as having severe (<10%; n = 6), moderate (10-25%; n = 15),
      or mild (26-50%; n = 39) FX deficiency. The patients underwent a total of 112
      procedures, 19 (17%) of which were managed with periprocedural treatment with one
      or more hemostatic agents. There were complications in 14 (13%) procedures
      (bleeding = 12, thrombosis = 1, death = 1). Baseline FX level was not predictive
      of bleeding risk; the only association with postintervention bleeding was central
      venous catheter placement. However, bleeding complications were relatively
      infrequent, particularly in patients with mild or moderate FX deficiency
      undergoing nonvascular procedures. Activated recombinant factor VII might be
      considered in patients undergoing major surgical procedures, but further
      experience is needed. Optimal management of AL patients with FX deficiency
      undergoing invasive procedures remains to be determined.

PMID- 20052751
TI  - Leukocytosis as a risk factor for thrombosis in myeloproliferative neoplasms
      biologically plausible but clinically uncertain.

PMID- 20052752
TI  - Syndrome to gene (S2G): in-silico identification of candidate genes for human
      diseases.
AB  - The identification of genomic loci associated with human genetic syndromes has
      been significantly facilitated through the generation of high density SNP arrays.
      However, optimal selection of candidate genes from within such loci is still a
      tedious labor-intensive bottleneck. Syndrome to Gene (S2G) is based on novel
      algorithms which allow an efficient search for candidate genes in a genomic
      locus, using known genes whose defects cause phenotypically similar syndromes.
      S2G (http://fohs.bgu.ac.il/s2g/index.html) includes two components: a phenotype
      Online Mendelian Inheritance in Man (OMIM)-based search engine that alleviates
      many of the problems in the existing OMIM search engine (negation phrases,
      overlapping terms, etc.). The second component is a gene prioritizing engine that
      uses a novel algorithm to integrate information from 18 databases. When the
      detailed phenotype of a syndrome is inserted to the web-based software, S2G
      offers a complete improved search of the OMIM database for similar syndromes. The
      software then prioritizes a list of genes from within a genomic locus, based on
      their association with genes whose defects are known to underlie similar clinical
      syndromes. We demonstrate that in all 30 cases of novel disease genes identified
      in the past year, the disease gene was within the top 20% of candidate genes
      predicted by S2G, and in most cases--within the top 10%. Thus, S2G provides
      clinicians with an efficient tool for diagnosis and researchers with a candidate
      gene prediction tool based on phenotypic data and a wide range of gene data
      resources. S2G can also serve in studies of polygenic diseases, and in finding
      interacting molecules for any gene of choice.

PMID- 20052753
TI  - The Human Variome Project (HVP) 2009 Forum "Towards Establishing Standards".
AB  - The May 2009 Human Variome Project (HVP) Forum "Towards Establishing Standards"
      was a round table discussion attended by delegates from groups representing
      international efforts aimed at standardizing several aspects of the HVP: mutation
      nomenclature, description and annotation, clinical ontology, means to better
      characterize unclassified variants (UVs), and methods to capture mutations from
      diagnostic laboratories for broader distribution to the medical genetics research
      community. Methods for researchers to receive credit for their effort at mutation
      detection were also discussed.

PMID- 20052754
TI  - CanProVar: a human cancer proteome variation database.
AB  - Identification and annotation of mutated genes or proteins involved in
      oncogenesis and tumor progression are crucial for both cancer biology and
      clinical applications. We have developed a human Cancer Proteome Variation
      Database (CanProVar) by integrating information on protein sequence variations
      from various public resources, with a focus on cancer-related variations (crVAR).
      We have also built a user-friendly interface for querying the database. The
      current version of CanProVar comprises 8,570 crVARs in 2,921 proteins derived
      from existing genome variation databases and recently published large-scale
      cancer genome resequencing studies. It also includes 41,541 non-cancer specific
      variations (ncsVARs) in 30,322 proteins derived from the dbSNP database.
      CanProVar provides quick access to known crVARs in protein sequences along with
      related cancer samples, relevant publications, data sources, and functional
      information such as Gene Ontology (GO) annotations for the proteins, protein
      domains in which the variation occurs, and protein interaction partners with
      crVARs. CanProVar also helps reveal functional characteristics of crVARs and
      proteins bearing these variations. Our analysis showed that crVARs were enriched
      in certain protein domains. We also showed that proteins bearing crVARs were more
      likely to interact with each other in the protein interaction network. CanProVar
      can be accessed from http://bioinfo.vanderbilt.edu/canprovar.

PMID- 20052755
TI  - Exciton Primer-mediated SNP detection in SmartAmp2 reactions.
AB  - Most commonly used intercalating fluorescent dyes in DNA detection are lacking
      any sequence specificity, whereas so-called Exciton Primers can overcome this
      limitation by functioning as "sequence-specific dyes." After hybridization to
      complementary sequences, the fluorescence of Exciton Primers provides sequence
      specific signals for real-time monitoring of amplification reactions. Applied to
      the SmartAmp2 mutation detection process, Exciton Primers show high signal
      strength with low background leading to a superior specificity and sensitivity
      compared to SYBR Green I. Signal strength can be further enhanced using multiple
      dyes within one Exciton Primer or use of multiple Exciton Primers in the same
      amplification reaction. Here we demonstrate the use of Exciton Primers for
      genotyping a single nucleotide polymorphism (SNP) in the VKORC1 locus (-1639G>A)
      relevant for Warfarin dosing as an example for Exciton Primers mediated
      genotyping by SmartAmp2. The genotyping assay can use only one labeled Exciton
      Primer for endpoint detection, or simultaneously by real-time monitoring detect
      wild-type and mutant alleles in a one-tube reaction using two Exciton Primers
      having different dyes. Working directly from blood samples, Exciton Primer
      mediated genotyping by SmartAmp2 offers superior solutions for rapid point-of
      care testing.

PMID- 20052756
TI  - Multiscale simulations of protein landscapes: using coarse-grained models as
      reference potentials to full explicit models.
AB  - Evaluating the free-energy landscape of proteins and the corresponding functional
      aspects presents a major challenge for computer simulation approaches. This
      challenge is due to the complexity of the landscape and the enormous computer
      time needed for converging simulations. The use of simplified coarse-grained (CG)
      folding models offers an effective way of sampling the landscape but such a
      treatment, however, may not give the correct description of the effect of the
      actual protein residues. A general way around this problem that has been put
      forward in our early work (Fan et al., Theor Chem Acc 1999;103:77-80) uses the CG
      model as a reference potential for free-energy calculations of different
      properties of the explicit model. This method is refined and extended here,
      focusing on improving the electrostatic treatment and on demonstrating key
      applications. These applications include: evaluation of changes of folding energy
      upon mutations, calculations of transition-states binding free energies (which
      are crucial for rational enzyme design), evaluations of catalytic landscape, and
      evaluations of the time-dependent responses to pH changes. Furthermore, the
      general potential of our approach in overcoming major challenges in studies of
      structure function correlation in proteins is discussed.

PMID- 20052757
TI  - Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders:
      dephosphorylation of serine 259 as the essential mechanism for mutant activation.
AB  - Noonan syndrome (NS) and related disorders are autosomal dominant disorders
      characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and
      mental retardation. The dysregulation of the RAS/MAPK pathway appears to be a
      common molecular pathogenesis of these disorders: mutations in PTPN11, KRAS, and
      SOS1 have been identified in patients with NS, those in KRAS, BRAF, MAP2K1, and
      MAP2K2 in patients with CFC syndrome, and those in HRAS mutations in Costello
      syndrome patients. Recently, mutations in RAF1 have been also identified in
      patients with NS and two patients with LEOPARD (multiple lentigines,
      electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary
      stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness)
      syndrome. In the current study, we identified eight RAF1 mutations in 18 of 119
      patients with NS and related conditions without mutations in known genes. We
      summarized clinical manifestations in patients with RAF1 mutations as well as
      those in NS patients withPTPN11, SOS1, or KRAS mutations previously reported.
      Hypertrophic cardiomyopathy and short stature were found to be more frequently
      observed in patients with RAF1 mutations. Mutations in RAF1 were clustered in the
      conserved region 2 (CR2) domain, which carries an inhibitory phosphorylation site
      (serine at position 259; S259). Functional studies revealed that the RAF1 mutants
      located in the CR2 domain resulted in the decreased phosphorylation of S259, and
      that mutant RAF1 then dissociated from 14-3-3, leading to a partial ERK
      activation. Our results suggest that the dephosphorylation of S259 is the primary
      pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain
      as well as of downstream ERK.

PMID- 20052758
TI  - Cell division cycle protein 73 homolog (CDC73) mutations in the
      hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors.
AB  - The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant
      disorder characterized by the occurrence of parathyroid tumors in association
      with ossifying fibromas of the maxilla and/or mandible. The gene responsible for
      HPT-JT, known as CDC73, was identified in 2002 and encodes a 531 amino acid
      protein known as parafibromin. Parafibromin is predominantly a nuclear protein
      that interacts directly with beta-catenin and also forms part of the RNA
      polymerase associated factor-1 complex (Paf1C) that regulates transcription.
      Heterozygous germline CDC73 mutations are detected in the majority of patients
      with HPT-JT, and the demonstration of loss of heterozygosity (LOH) at the CDC73
      locus in tumors from affected individuals is consistent with a tumor suppressor
      role. Somatic CDC73 mutations are a frequent finding in nonfamilial (i.e.,
      sporadic) parathyroid carcinomas and have also been reported in benign sporadic
      parathyroid tumors as well as sporadic renal and fibro-osseous jaw tumors. To
      date, 111 independent CDC73 mutations have been identified (68 germline; 38
      somatic; 5 undefined), and these occur throughout the coding region and splice
      sites of the CDC73 gene, with the majority (>80%) predicting premature truncation
      of the parafibromin protein. These CDC73 mutations, together with their clinical
      and biological relevance, are reviewed.

PMID- 20052759
TI  - Plectin expression patterns determine two distinct subtypes of epidermolysis
      bullosa simplex.
AB  - Plectin is a cytoskeletal linker protein that has a dumbbell-like structure with
      a long central rod and N- and C-terminal globular domains. Mutations in the gene
      encoding plectin (PLEC1) cause two distinct autosomal recessive subtypes of
      epidermolysis bullosa (EB): EB simplex with muscular dystrophy (EBS-MD), and EB
      simplex with pyloric atresia (EBS-PA). Here, we demonstrate that normal human
      fibroblasts express two different plectin isoforms including full-length and
      rodless forms of plectin. We performed detailed analysis of plectin expression
      patterns in six EBS-MD and three EBS-PA patients. In EBS-PA, expression of all
      plectin domains was found to be markedly attenuated or completely lost; in EBS
      MD, the expression of the N- and C-terminal domains of plectin remained
      detectable, although the expression of rod domains was absent or markedly
      reduced. Our data suggest that loss of the full-length plectin isoform with
      residual expression of the rodless plectin isoform leads to EBS-MD, and that
      complete loss or marked attenuation of full-length and rodless plectin expression
      underlies the more severe EBS-PA phenotype. These results also clearly account
      for the majority of EBS-MD PLEC1 mutation restriction within the large exon 31
      that encodes the plectin rod domain, whereas EBS-PA PLEC1 mutations are generally
      outside exon 31.

PMID- 20052760
TI  - Microsatellite instability in the peripheral blood leukocytes of HNPCC patients.
AB  - Most hereditary nonpolyposis colorectal cancer (HNPCC) patients inherit a
      defective allele of a mismatch repair (MMR) gene, usually MLH1 or MSH2, resulting
      in high levels of microsatellite instability (MSI-H) in the tumors. Presence of
      MSI in the normal tissues of mutation carriers has been controversial. Here we
      directly compare MSI in the peripheral blood leukocyte (PBL) DNA of seven HNPCC
      patients carrying different types of pathogenic MMR mutations in MLH1 and MSH2
      genes with the PBL DNA of normal age-matched controls and of patients with
      sporadic colorectal cancer (SCRC). Small pool PCR (SP-PCR) was used studying
      three microsatellite loci for at least 100 alleles each in most samples. The
      average frequencies of mutant microsatellite fragments in each HNPCC patient
      (0.04-0.24) were significantly higher (p<0.01) relative to their age-matched
      normal controls with mutant frequencies (MF) from 0.00 to 0.06, or SCRC patients
      (MF from 0.01-0.03). The data support the conclusions that higher MF in the PBL
      DNA of HNPCC patients is real and reproducible, may vary in extent according to
      the type of germline MMR mutation and the age of the individual, and provide a
      possible genetic explanation for anticipation in HNPCC families.

PMID- 20052761
TI  - Extended runs of homozygosity at 17q11.2: an association with type-2 NF1
      deletions?
AB  - Large deletions in the NF1 gene region at 17q11.2 are caused by nonallelic
      homologous recombination (NAHR). The recurrent type-2 NF1 deletions span 1.2 Mb,
      with breakpoints in the SUZ12 gene and SUZ12P. Type-2 NF1 deletions occur
      preferentially during mitosis and are associated with somatic mosaicism. A panel
      of 16 type-2 NF1 deletions was used as a model system in which to investigate
      whether extended homozygosity across 17q11.2 might be associated with somatic
      deletion. Using SNP arrays, a 3.2 Mb interval encompassing the NF1 deletion
      region was found to harbor runs of homozygosity (ROHs) in different human
      populations. However, ROHs >or=500 kb directly flanking the NF1 deletion region
      on both sides were not found to occur disproportionately in NF1 patients
      harboring type-2 deletions compared to controls. Although low allelic diversity
      in 17q11.2 is unlikely to be a key factor in promoting NAHR-mediated somatic type
      2 deletions, a specific ROH of 588 kb (roh1), located some 525 kb proximal to the
      deletion interval, was found to occur more frequently (P=0.012) in the type-2
      deletion patients compared with controls. We postulate that roh1 may act
      remotely, via an as yet unknown mechanism, to increase the frequency of somatic
      recombination between the distally duplicated SUZ12 sequences.

PMID- 20052762
TI  - In silico functional profiling of human disease-associated and polymorphic amino
      acid substitutions.
AB  - An important challenge in translational bioinformatics is to understand how
      genetic variation gives rise to molecular changes at the protein level that can
      precipitate both monogenic and complex disease. To this end, we compiled datasets
      of human disease-associated amino acid substitutions (AAS) in the contexts of
      inherited monogenic disease, complex disease, functional polymorphisms with no
      known disease association, and somatic mutations in cancer, and compared them
      with respect to predicted functional sites in proteins. Using the sequence
      homology-based tool SIFT to estimate the proportion of deleterious AAS in each
      dataset, only complex disease AAS were found to be indistinguishable from neutral
      polymorphic AAS. Investigation of monogenic disease AAS predicted to be
      nondeleterious by SIFT were characterized by a significant enrichment for
      inherited AAS within solvent accessible residues, regions of intrinsic protein
      disorder, and an association with the loss or gain of various posttranslational
      modifications. Sites of structural and/or functional interest were therefore
      surmised to constitute useful additional features with which to identify the
      molecular disruptions caused by deleterious AAS. A range of bioinformatic tools,
      designed to predict structural and functional sites in protein sequences, were
      then employed to demonstrate that intrinsic biases exist in terms of the
      distribution of different types of human AAS with respect to specific structural,
      functional and pathological features. Our Web tool, designed to potentiate the
      functional profiling of novel AAS, has been made available at
      http://profile.mutdb.org/.

PMID- 20052763
TI  - Ex vivo splicing assays of mutations at noncanonical positions of splice sites in
      USHER genes.
AB  - Molecular diagnosis in Usher syndrome type 1 and 2 patients led to the
      identification of 21 sequence variations located in noncanonical positions of
      splice sites in MYO7A, CDH23, USH1C, and USH2A genes. To establish experimentally
      the splicing pattern of these substitutions, whose impact on splicing is not
      always predictable by available softwares, ex vivo splicing assays were
      performed. The branch-point mapping strategy was also used to investigate further
      a putative branch-point mutation in USH2A intron 43. Aberrant splicing was
      demonstrated for 16 of the 21 (76.2%) tested sequence variations. The mutations
      resulted more frequently in activation of a nearby cryptic splice site or use of
      a de novo splice site than exon skipping (37.5%). This study allowed the
      reclassification as splicing mutations of one silent (c.7872G>A (p.Glu2624Glu) in
      CDH23) and four missense mutations (c.2993G>A (p.Arg998Lys) in USH2A, c.592G>A
      (p.Ala198Thr), c.3503G>C [p.Arg1168Pro], c.5944G>A (p.Gly1982Arg) in MYO7A),
      whereas it provided clues about a role in structure/function in four other cases:
      c.802G>A (p.Gly268Arg), c.653T>A (p.Val218Glu) (USH2A), and c.397C>T
      (p.His133Tyr), c.3502C>T (p.Arg1168Trp) (MYO7A). Our data provide insights into
      the contribution of splicing mutations in Usher genes and illustrate the need to
      define accurately their splicing outcome for diagnostic purposes.

PMID- 20052764
TI  - Inferring the functional effects of mutation through clusters of mutations in
      homologous proteins.
AB  - Inferring functional consequences is a bottleneck in high-throughput cancer
      mutation discovery and genetic association studies. Most polymorphisms and
      germline mutations are unlikely to have functionally significant consequences.
      Most cancer somatic mutations do not contribute to tumorigenesis and are not
      under selective pressure. Identifying and understanding functionally important
      mutations can clarify disease biology and lead to new therapeutic and diagnostic
      opportunities. We investigated the extent to which protein mutations with
      functional consequences are enriched in clusters at conserved positions across
      related proteins. We found that disease-causing mutations form clusters more than
      random mutations or single nucleotide polymorphisms, confirming that mutation
      hotspots occur at the domain level. In addition to helping to identify
      functionally significant mutations, analysis of clustered mutations can indicate
      the mechanism and consequences for protein function. Our analysis focused on
      somatic cancer mutations suggests functional impact for many, including singleton
      mutations in FGFR1, FGFR3, GFI1B, PIK3CG, RALB, RAP2B, and STK11. This provides
      evidence and generates mechanistic hypotheses for the contribution of such
      mutations to cancer. The same approach can be applied to mutations suspected of
      involvement in other diseases. An interactive Web application for browsing
      mutation clusters is available at http://www.mcluster.org.

PMID- 20052765
TI  - The neuronal ceroid lipofuscinosis protein CLN5: new insights into cellular
      maturation, transport, and consequences of mutations.
AB  - Neuronal ceroid lipofuscinoses (NCLs) represent a group of children's inherited
      neurodegenerative disorders caused by mutations in at least eight different
      genes. Mutations in the CLN5 gene result in the Finnish variant late infantile
      NCL characterized by gradual loss of vision, epileptic seizures, and mental
      deterioration. The CLN5 gene encodes a lysosomal glycoprotein of unidentified
      function. In this study, we have used both transient and stable expression
      systems for the characterization of CLN5, focusing on the localization,
      processing, and intracellular trafficking. We show that CLN5 is proteolytically
      cleaved, and that the mature polypeptide is transported to the lysosomes. Our
      data provide the first evidence that soluble CLN5 protein can also undergo
      mannose-6-phosphate receptor-independent trafficking to the lysosomes. We studied
      the localization and maturation of the CLN5 carrying the previously
      uncharacterized vLINCL disease causing mutations in HeLa cells. All analyzed
      disease mutations disturb the lysosomal trafficking of the mutated CLN5 proteins.
      The level of lysosomal targeting does not correlate, however, to disease onset,
      indicating that CLN5 may also function outside lysosomes. This study furthers our
      understanding of the basic properties of the CLN5 protein, necessary for the
      characterization of the consequences of disease mutations and for the planning of
      future therapies for vLINCL.

PMID- 20052766
TI  - Complete ascertainment of intragenic copy number mutations (CNMs) in the CFTR
      gene and its implications for CNM formation at other autosomal loci.
AB  - Over the last 20 years since the discovery of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene, more than 1,600 different putatively
      pathological CFTR mutations have been identified. Until now, however, copy number
      mutations (CNMs) involving the CFTR gene have not been methodically analyzed,
      resulting almost certainly in the underascertainment of CFTR gene duplications
      compared with deletions. Here, high-resolution array comparative genomic
      hybridization (averaging one interrogating probe every 95 bp) was used to analyze
      the entire length of the CFTR gene (189 kb) in 233 cystic fibrosis chromosomes
      lacking conventional mutations. We succeeded in identifying five duplication CNMs
      that would otherwise have been refractory to analysis. Based upon findings from
      this and other studies, we propose that deletion and duplication CNMs in the
      human autosomal genome are likely to be generated in the proportion of
      approximately 2-3:1. We further postulate that intragenic gene duplication CNMs
      in other disease loci may have been routinely underascertained. Finally, our
      analysis of +/-20 bp flanking each of the 40 CFTR breakpoints characterized at
      the DNA sequence level provide support for the emerging concept that non-B DNA
      conformations in combination with specific sequence motifs predispose to both
      recurring and nonrecurring genomic rearrangements.

PMID- 20052767
TI  - An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a
      genotype-phenotype study.
AB  - L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an
      autosomal recessive mode of inheritance. Affected individuals only have
      neurological manifestations, including psychomotor retardation, cerebellar
      ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can
      be made based on magnetic resonance imaging (MRI), biochemical analysis, and
      mutational analysis of L2HGDH. About 200 patients with elevated concentrations of
      2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of
      2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83
      families) were included. Clinical information on 61 patients was obtained via
      questionnaires. In 82 families the mutations were detected by direct sequence
      analysis and/or multiplex ligation dependent probe amplification (MLPA),
      including one case where MLPA was essential to detect the second allele. In
      another case RT-PCR followed by deep intronic sequencing was needed to detect the
      mutation. Thirty-five novel mutations as well as 35 reported mutations and 14
      nondisease-related variants are reviewed and included in a novel Leiden Open
      source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH).
      Every user can access the database and submit variants/patients. Furthermore, we
      report on the phenotype, including neurological manifestations and urinary levels
      of L2HG, and we evaluate the phenotype-genotype relationship.

PMID- 20052768
TI  - New method for age estimation of developmental defects of enamel formation in
      living populations.
AB  - Histologically based age of occurrence estimates for developmental defects of
      enamel (DDE) are raising questions about the continued utility of traditional
      macroscopic methods; however, the new techniques are not appropriate for use on
      living populations. This study, using methodology suitable for noninvasive use on
      living populations, compares assignment of defect timing using a histologically
      informed macroscopic method (HIMM) versus traditional methodology (TM). For this
      Southern African population, TM estimates later median age of DDE occurrence than
      HIMM (Z-score: -13.565, P < 0.000) and modal age is 1 year earlier. HIMM allows
      for continued collection of DDE in living populations with the added benefit of
      more precise timing of enamel development. Accuracy for estimating general
      stressors during childhood is necessary for construction of diachronic analyses.

PMID- 20052769
TI  - Protective effects of eicosapentaenoic acid on genotoxicity and oxidative stress
      of cyclophosphamide in mice.
AB  - The aim of this article is to elucidate the mechanism by which eicosapentaenoic
      acid (EPA) acts against cyclophosphamide (CP)-induced effects. The prevalence of
      micronuclei, the extent of lipid peroxidation, and the status of the antioxidant
      enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX)
      in both liver and serum of mice were used as intermediate biomarkers of
      chemoprotection. Lipid peroxidation and associated compromised antioxidant
      defenses (CAT and GPX) in CP treated mice were observed in the liver, serum, and
      were accompanied by increased prevalence of micronuclei in bone marrow. The
      number of MN was significantly different (p < 0.01) between the groups treated
      with CP (group III, IV, V, VI) and the solvent control (group II) (3.2 +/-
      0.70/00). There was a dose-dependent reduction in formation CP induced
      micronuclei by treatment with 100, 200, or 300 mg EPA/kg BW mice. Activities of
      SOD, CAT, and extent of lipid peroxidation were statistically different in liver
      cells of mice exposed to EPA only with CP compared with the CP group (group III).
      The present findings imply that EPA may be a potential antigenotoxic, antioxidant
      and chemopreventive agent and could be used as an adjuvant in chemotherapeutic
      applications.

PMID- 20052770
TI  - Biomarker analyses in caged and wild fish suggest exposure to pollutants in an
      urban area with a landfill.
AB  - An unexpectedly high frequency of skeletal deformations in brown trout has
      previously been observed in the brook Vallkarrabacken in southern Sweden.
      Environmental pollutants from storm water and leachate from an old landfill have
      been suggested as responsible for the observed deformations. Biomarkers in farmed
      rainbow trout, placed in tanks with water supplied from the brook, were used to
      investigate if exposure to pollutants may induce toxic responses in fish.
      Furthermore, biomarkers were also measured in wild brown trout that were caught
      in the brook. The most important finding was that the hepatic ethoxyresorufin-O
      deethylase (EROD) activity was five to seven times higher for rainbow trout and
      brown trout in exposed areas compared to reference sites (P<0.001). Analyses of
      bile in rainbow trout showed that the concentration of PAH-metabolites was two to
      three times higher (P<0.001) in the exposed areas. However, due to their smaller
      size and the feeding status, only insufficient amounts of bile could be retrieved
      from the wild brown trout. The study provides evidence for pollution in parts of
      Vallkarrabacken. It is therefore possible that the previously observed high
      frequency of skeletal damage have been caused by pollutants. The methodology with
      farmed rainbow trout in flow through tanks worked well and provided more
      information about the occurrence of pollutants in Vallkarrabacken than the data
      from brown trout. The main reasons for this were that the size and the feeding
      status of the fish could be controlled. This allowed a total of 21 biomarkers to
      be analyzed in farmed rainbow trout compared to only five in wild brown trout.
      Furthermore, the use of farmed fish eliminates the risk of migration, which may
      otherwise bias the data when wild fish are used.

PMID- 20052771
TI  - Peripubertal exposure to low doses of tributyltin chloride affects the
      homeostasis of serum T, E2, LH, and body weight of male mice.
AB  - Previous studies have shown that tributyltin could act as an endocrine disruptor
      in mammals. However, the data on the low-dose effect of tributyltin in animals
      are still lacking. The objective of this study was to demonstrate the endocrine
      disruption induced by low levels of tributyltin chloride (TBTCl) in male KM mice.
      The animals were treated with 0.05 or 0.5 mg TBTCl/kg body weight/3 days from
      postnatal days (PNDs) 24 to 45, and killed on PNDs 49 and 84, respectively. Mice
      treated with 0.5 mg TBTCl/kg exhibited decreased serum and intratesticular
      testosterone (T) levels on PND 49 and then followed by an obvious recovery on PND
      84. Furthermore, mice treated with 0.05 mg TBTCl/kg showed reduced serum 17beta
      estradiol (E2) levels on PND 49. However, treatments with TBTCl resulted in a
      dose-dependent increase in serum E2 concentration of the mice on PND 84.
      Administration of TBTCl also decreased levels of serum luteinizing hormone and
      intratesticular E2 on PND 84. In addition, mice exposed to 0.05 mg/kg TBTCl
      exhibited an increase in body weight in the late stage of the experiment. These
      results indicate that treatment with low doses of TBTCl could disturb hormone
      homeostasis and body weight gain in rodents, and exposure to different levels of
      TBTCl might have different effects on changing some physiologic parameters.

PMID- 20052773
TI  - Bilateral internal carotid artery occlusions in a pediatric patient with
      refractory acute myeloid leukemia.
AB  - Thromboembolism is a well-known complication of cancer including acute myeloid
      leukemia (AML) especially in patients with high myeloblast counts. However,
      spontaneous vaso-occlusion in the main arteries is very rare especially in
      patients with low blast counts and no pre existing vasculopathy. We report the
      case of a 3-year-old male with refractory AML who developed spontaneous bilateral
      internal carotid artery occlusion with diffuse cerebral infarcts. Strokes are
      rarely secondary to spontaneous carotid artery thrombosis and few cases have been
      reported in the literature.

PMID- 20052772
TI  - The anti-inflammatory effects of adiponectin are mediated via a heme oxygenase-1
      dependent pathway in rat Kupffer cells.
AB  - Altered expression and activity of immunomodulatory cytokines plays a major role
      in the pathogenesis of alcoholic liver disease. Chronic ethanol feeding increases
      the sensitivity of Kupffer cells, the resident hepatic macrophage, to
      lipopolysaccharide (LPS), leading to increased tumor necrosis factor alpha (TNF
      alpha) expression. This sensitization is normalized by treatment of primary
      cultures of Kupffer cells with adiponectin, an anti-inflammatory adipokine. Here
      we tested the hypothesis that adiponectin-mediated suppression of LPS signaling
      in Kupffer cells is mediated via an interleukin-10 (IL-10)/heme oxygenase-1 (HO
      1) pathway after chronic ethanol feeding. Knockdown of IL-10 expression in
      primary cultures of Kupffer cells with small interfering RNA (siRNA) prevented
      the inhibitory effect of globular adiponectin (gAcrp) on LPS-stimulated TNF-alpha
      expression. gAcrp increased IL-10 mRNA and protein expression, as well as
      expression of the IL-10 inducible gene, HO-1; expression was higher in Kupffer
      cells from ethanol-fed rats compared with pair-fed controls. Although IL-10
      receptor surface expression on Kupffer cells was not affected by ethanol feeding,
      IL-10-mediated phosphorylation of STAT3 and expression of HO-1 was higher in
      Kupffer cells after ethanol feeding. Inhibition of HO-1 activity, either by
      treatment with the HO-1 inhibitor zinc protoporphyrin or by siRNA knockdown of HO
      1, prevented the inhibitory effect of gAcrp on LPS-stimulated TNF-alpha
      expression in Kupffer cells. LPS-stimulated TNF-alpha expression in liver was
      increased in mice after chronic ethanol exposure. When mice were treated with
      cobalt protoporphyrin to induce HO-1 expression, ethanol-induced sensitivity to
      LPS was ameliorated. CONCLUSION: gAcrp prevents LPS-stimulated TNF-alpha
      expression in Kupffer cells through the activation of the IL-10/STAT3/HO-1
      pathway. Kupffer cells from ethanol-fed rats are highly sensitive to the anti
      inflammatory effects of gAcrp; this sensitivity is associated with both increased
      expression and sensitivity to IL-10.

PMID- 20052774
TI  - Intraoperative examination (IOE) in pediatric extracranial tumors.
AB  - BACKGROUND AND OBJECTIVES: Intraoperative evaluation of surgical specimens by
      frozen sections (IOE) is required to distinguish benign and malignant lesions,
      assess surgical margins, and determine sample adequacy of biopsies. In the last
      years, it has been used also for therapeutic decisions, particularly in children,
      who may need other ancillary procedures, in case of malignancies. Our purpose was
      the evaluation of diagnostic accuracy, limits, and different role of IOE in
      pediatric pathology. PATIENTS AND METHODS: From 1990 to 2001, 416 IOEs were
      performed in 341 children, affected by lymph node pathology, soft tissue tumors,
      neuroblastic tumors, gonadal germ cell, and stromal tumors, hepatic lesions,
      renal tumors, and others; the technique was also used to assess surgical margins
      during major surgeries. IOEs were obtained from Tru-cut biopsies (<1 cm(3)), wide
      biopsies (>1 cm(3)), or from the whole lesions, and the subsequent final
      diagnoses were classified as conordant, discordant, and deferred. RESULTS: Three
      hundred seventy cases (88.9%) were concordant, 10 (2.4%) discordant, and 36
      (8.6%) deferred. The disagreement was found in two small lymph node samples,
      three soft tissue tumors, one hepatoblastoma, one metastasis, and three surgical
      margins. The deferred diagnoses were related to lymph node and soft tissue
      lesions. CONCLUSIONS: IOE in pediatric oncology may integrate the diagnostic
      process and supports the therapeutic guidelines of different tumors. In our
      study, the diagnostic concordance was satisfactory. A rational use of the
      technique and the awareness of its limits are, however, prerequisites to avoid
      the risk of overtreatment.

PMID- 20052775
TI  - Neuropsychological functioning of children treated with intensive chemotherapy
      followed by myeloablative consolidation chemotherapy and autologous hematopoietic
      cell rescue for newly diagnosed CNS tumors: an analysis of the Head Start II
      survivors.
AB  - BACKGROUND: To evaluate the neuropsychological late effects amongst survivors
      treated on the Head Start II protocol between 1997 and 2003. PROCEDURES: Forty
      nine patients (mean age 2.9 years) diagnosed with a malignant brain tumor
      underwent baseline neuropsychological assessment prior to autologous
      hematopoietic cell transplantation (AuHCT). Twenty-six survivors were retested
      after 3 years of follow-up as 20 patients did not survive. Patients were
      evaluated for intelligence, academic achievement, receptive language, visual
      motor integration (VMI), learning/memory, social-emotional and behavioral
      functioning based upon age at testing. RESULTS: Overall intelligence and VMI at
      baseline were low average while verbal and non-verbal intelligence, academic
      achievement, and receptive vocabulary were in average range. Parents reported
      social-emotional and behavioral functioning within normal limits. Serial testing
      revealed Full Scale (FSIQ)/Mental Development Index (MDI), Verbal (VIQ), and
      Performance (PIQ) Intelligence to be generally stable over 3-year follow-up.
      Group-average analysis at follow-up demonstrated low average intelligence,
      academic achievement, receptive language, and VMI. Age at diagnosis was
      positively correlated with internalizing symptoms and visual immediate memory,
      while time since diagnosis was inversely correlated with FSIQ, VIQ, PIQ, reading
      and delayed verbal memory. Craniospinal irradiation (CSI) was avoided in two
      thirds of patients. CONCLUSION: Induction, with or without intensification using
      intravenous methotrexate, followed by myeloablative consolidation chemotherapy
      with AuHCT, may avoid or delay CSI, with possible stabilization of
      neuropsychological functioning, including those younger at diagnosis. Continued
      follow-up is necessary to determine the preservation of neuropsychological,
      academic, social-emotional and behavioral functioning.

PMID- 20052776
TI  - Severe ehrlichia infection in pediatric oncology and stem cell transplant
      patients.
AB  - Ehrlichiosis, a tickborne illness transmitted by tick vectors Amblyomma
      americanum and Ixodes scapularis, can be acquired in endemic areas. Clinical
      manifestations range from asymptomatic to fulminant in nature. We report three
      cases of ehrlichiosis in pediatric oncology patients, one of whom was a stem cell
      transplant recipient. Early symptoms included fever, malaise, and vague
      gastrointestinal symptoms. Laboratory abnormalities were initially attributed to
      chemotherapy toxicity. Illness was severe in all three patients and one patient
      died even after initiation of doxycycline. These cases emphasize the need for a
      high index of suspicion for tickborne illness in oncology patients, and the
      importance of a low threshold for starting empiric treatment before confirming
      the diagnosis.

PMID- 20052777
TI  - Trends in childhood cancer incidence and mortality in urban Shanghai, 1973-2005.
AB  - BACKGROUND: To describe trends in cancer incidence and mortality among children
      less than 15 years of age in urban Shanghai between 1973 and 2005. PROCEDURE:
      Annual rates of cancer incidence were calculated per 1,000,000 children for 3
      year intervals between 1973 and 2005. Linear regression models were used to
      analyze the annual percent change (APC) in incidence and mortality across these
      distinct intervals. RESULTS: For all cancers combined, the incidence rate during
      the observed time period did not substantially change in urban Shanghai. Rates
      for the incidence of individual cancer did exhibit variations. Leukemia incidence
      remained relatively stable but the incidence of myeloid leukemia decreased
      sharply in both males (APC -8.6%) and females (APC -9.5%). The rate of NHL varied
      little among males with APC 2.1% and modestly increased among females with APC
      9.3%. Anatomic sites that only occasionally demonstrate malignancy, bone and
      joints in males and endocrines in females, showed upward trends in incidence. A
      significant reduction in liver cancer incidence in males was observed. Examining
      mortality rates, all cancer mortality decreased by -6.0% annually in males and by
      -3.9% in females. This trend was mainly due to the reduction in mortality for
      leukemia, particularly the myeloid subtype, which decreased in males (APC -7.2%)
      and females (APC -7.3%). CONCLUSIONS: Childhood cancer incidence rates showed no
      substantial changes but mortality demonstrated a dramatic reduction during the
      observed time period, suggesting an improvement in both childhood cancer
      diagnosis and treatment.

PMID- 20052778
TI  - Decision analysis to compare treatment strategies for Stage I/favorable histology
      Wilms tumor.
AB  - BACKGROUND: Decision analysis was used to clarify differences in survival and
      complication rates comparing surgery alone versus surgery plus chemotherapy for
      Stage I, favorable histology Wilms tumor patients. PROCEDURE: A state transition
      model was used to simulate treatment with nephrectomy-only, nephrectomy with
      adjuvant vincristine (VCR) or with vincristine plus dactinomcyin (NWTS Regimen
      EE4A). Rates of relapse and complications of therapy were obtained from the
      literature. In sensitivity analysis, the model was probed for the value(s) at
      which the treatment of choice changes. RESULTS: The overall survival (OS) is
      essentially the same for patients treated with any of the three strategies
      (OS(Nephrectomy) = 98.8%; OS(EE4A) = 98.8%; OS(VCR) = 98.6%). Rates of serious
      long-term complications in the surviving population are also similar across
      treatment strategies (nephrectomy = 1.4%; VCR = 1.2%; EE4A = 0.3%). Both the
      progression and salvage rates after nephrectomy-only would have to be much worse
      than expected for nephrectomy-only to be an unacceptable strategy. CONCLUSIONS:
      The differences in overall survival and rates of long-term complications between
      the three different initial strategies were negligible in the model. Based on
      this analysis, it was decided by the Children's Oncology Group that it was
      acceptable to continue to include nephrectomy without adjuvant chemotherapy as an
      experimental arm of the low risk Wilms tumor protocol with stringent eligibility
      criteria and close follow-up. Decision analysis can have a role in clinical trial
      design by making the tradeoffs between strategies more explicit. The robustness
      of these conclusions can be tested by widely varying the underlying assumptions.

PMID- 20052779
TI  - Neonatal cholestasis and glucose-6-P-dehydrogenase deficiency.
AB  - We report a Caucasian neonate with chronic non-spherocytic hemolytic anemia due
      to a class I G6PD deficiency. A novel mutation missense mutation in exon eight of
      the G6PD gene was detected (c.827C>T p.Pro276Leu). Bilirubin peaked on day 5 at
      24 mg/dl with a conjugated bilirubin of 17 mg/dl. Jaundice resolved within 4
      weeks. A detailed work-up failed to reveal other specific factors contributing to
      cholestasis. Severe hemolytic disease of the newborn may cause cholestasis even
      in the absence of associated primary hepato-biliary disease.

PMID- 20052781
TI  - Chernobyl: Consequences of the Catastrophe for People and the Environment.

PMID- 20052780
TI  - Phase I trial of sargramostim in pediatric Crohn's disease.
AB  - BACKGROUND: Improving granulocyte function may represent an effective therapy for
      Crohn's disease (CD). We performed a Phase I-2 trial of sargramostim (SRG) in
      children with CD. METHODS: This was multicenter, open-label study in 6-16-year
      old patients with moderate to severely active CD. Patients received either 4 or 6
      microg/kg SRG subcutaneously daily for 8 weeks, with and without concomitant
      corticosteroids (CS). The primary endpoint was identification of a safe and
      tolerable dose in children. The secondary endpoint was establishment of the
      pharmacokinetics (PK). Efficacy, a tertiary endpoint, was measured by the
      Pediatric CD Activity Index (PCDAI). Response was defined as a decrease from
      baseline of > or =12.5 points and remission as absolute PCDAI of < or =10.
      RESULTS: In all, 22 patients were enrolled: 12 and 10 received 4 and 6 mg/kg,
      respectively; 19 completed the course. Both doses were found to be safe and well
      tolerated. Mild injection-site reactions occurred in 90% of patients. Three
      patients required dose reductions due to elevated absolute neutrophil counts.
      Following 4 microg/kg the mean area under the curve (AUC) was 2.64 and 2.80
      ngh/mL for the 6-11- and 12-16-year-old groups, respectively. The mean half-life
      (t(1/2)) was 1.22 and 1.59 hours, respectively. Following 6 microg/kg, the mean
      AUC was 5.01 ngh/mL for the 12-16-year-old group, a 1.8-fold increase. A total of
      16/18 patients (88%) achieved remission or response. CONCLUSIONS: Sargramostim at
      both 4 and 6 mg/kg was well tolerated. PK analysis suggested dose proportionality
      unaffected by CS exposure. Remission and response data are encouraging, but
      further trials are needed to assess efficacy.

PMID- 20052782
TI  - Proceedings of the Regensburg Conference. September 5-6, 2008. Regensburg,
      Germany.

PMID- 20052783
TI  - Proceedings of the Speed and Safety in Drug Discovery Symposium. November 26,
      2009. London, United Kingdom.

PMID- 20052784
TI  - Challenges in nano- micro- and macro-systems. Proceedings of the 7th Central
      European Symposium on Pharmaceutical Technology and Biodelivery Systems.
      September 18-20, 2008. Ljubljana, Slovenia.

PMID- 20052785
TI  - Proceedings of an international symposium on neurorobotics. Summer 2008.
      Freiburg, Germany.

PMID- 20052786
TI  - Nutrition - integral part of the treatment of the important diseases. Proceedings
      of the Fourth Conference. October 1, 2009. Ceske Budejovice, Czech Republic.

PMID- 20052787
TI  - Proceedings of the 17th International Conference on Chelation (ICOC) for the
      Treatment of Thalassemia, Cancer and Other Diseases Related to Metal and Free
      Radical Imbalance and Toxicity. November 2007. Shenzhen, China.

PMID- 20052788
TI  - Correction: glucose control and cardiovascular disease in type 2 diabetes.

PMID- 20052789
TI  - Proceedings of the Second Renewable Energy International Conference. October 13
      18, 2008. Busan, Korea.

PMID- 20052790
TI  - Proceedings of the Symposium on the Mechanics of Growth and Remodeling in Native
      and Engineered Tissues. Marco Island, Florida, USA. June 25-29, 2008.

PMID- 20052791
TI  - Proceedings of the Annual Meeting of the American Association of Hip and Knee
      Surgeons. Dallas, Texas.

PMID- 20052792
TI  - First food: the essential role of breastfeeding. Proceedings of the First Annual
      Summit on Breastfeeding. June 11-12, 2009. Washington, D.C., USA.

PMID- 20052793
TI  - Proceedings of an International Menopause Society Workshop. Pisa, Italy.

PMID- 20052794
TI  - Evidence-based review and discussion points.

PMID- 20052795
TI  - 200th anniversary volume, issue 1: behavioural sciences and neuropsychology.

PMID- 20052796
TI  - When my child was born: cross-cultural reactions to the birth of a child with
      cleft lip and/or palate.
AB  - OBJECTIVE: To compare across cultures the maternal reactions toward the birth of
      children with cleft lip and/or palate. DESIGN: An adaptation of When My Child Was
      Born, a Likert-type scale designed to assess reactions to the birth of a child,
      was used to survey the target populations. SETTING: The surveys were administered
      between February 2006 and February 2008 at four hospitals: the Faculty of
      Medicine Hospital, Chiang Mai, Thailand; Sappasitprasong Hospital, Ubon
      Ratchathani, Thailand; the No. 5 Affiliated Hospital to Xinjiang Medical College,
      Urumqi, China; and Santa Monica Hospital,Pereira, Colombia. PARTICIPANTS: Thai (n
      = 22), Chinese (n = 25), Uygur (n = 15), and Colombian (n= 36) biological mothers
      completed the survey. A historical cohort of American mothers (n = 99) was used
      for comparison. MAIN OUTCOME MEASURE(S): The primary study outcome measure was
      the mean maternal affect score, which was calculated from the individual
      responses of study participants. RESULTS: The mean maternal affect scores for the
      Thai, Chinese, Uygur, and Colombian mothers were 3.68 6 0.38, 2.97 6 0.52, 3.40 6
      0.47, and 3.51 6 0.61,respectively. The American cohort score was 3.44 6 0.67.
      Analysis of variance testing indicated that these groups were not equal (p ,
      .0001). There were statistically significant differences between groups (p ,
      .05). CONCLUSIONS: Maternal reactions to the birth of cleft children are
      different across cultures. These differences must be considered when
      administering care on international surgical missions.

PMID- 20052797
TI  - Salaries on the rise--but so are the hours.

PMID- 20052799
TI  - Systems biology. Proceedings of Nobel Symposium 146. June 22-27, 2009. Sanga
      Saby, Sweden.

PMID- 20052800
TI  - The phenotype of murine wound  macrophages.
AB  - The phenotype of wound macrophages has not been studied by direct examination of
      these cells, yet macrophages recruited to sites of injury are described as
      alternatively activated macrophages, requiring IL-4 or IL-13 for phenotypic
      expression. This study characterized wound macrophage phenotype in the PVA sponge
      wound model in mice. Eighty-five percent of wound macrophages isolated 1 day
      after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed
      this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of
      alternative activation,including mannose receptor, dectin-1, arginase 1,and Ym1,
      but did not contain iNOS. Day 1 wound macrophages produced more TNF-alpha, more
      IL-6, and less TGF-beta than Day 7 wound macrophages. Wound macrophages did not
      produce IL-10. The cytokines considered necessary for alternative activation of
      macrophages,IL-4 and IL-13, were not detected in the wound environment and were
      not produced by wound cells.Wound macrophages did not contain PStat6. Wound
      fluids inhibited IL-13-dependent phosphorylation of Stat6 and contained IL
      13Ralpha2, a soluble decoy receptor for IL-13. The phenotype of wound macrophages
      was not altered in mice lacking IL-4Ralpha, which is required for Stat6-dependent
      signaling of IL-4 and IL-13.Wound macrophages exhibit a complex phenotype,which
      includes traits associated with alternative and classical activation and changes
      as the wound matures.The wound macrophage phenotype does not require IL-4 or IL
      13.

PMID- 20052802
TI  - When two is better than one: macrophages  and neutrophils work in concert in
      innate  immunity as complementary and  cooperative partners of a myeloid 
      phagocyte system.
AB  - The antimicrobial effector activity of phagocytes is crucial in the host innate
      defense against infection, and the classic view is that the phagocytes operating
      against intracellular and extracellular microbial pathogens are,respectively,
      macrophages and neutrophils. As a result of the common origin of the two
      phagocytes, they share several functionalities, including avid
      phagocytosis,similar kinetic behavior under inflammatory/infectious conditions,
      and antimicrobial and immunomodulatory activities. However, consequent to
      specialization during their differentiation, macrophages and neutrophils acquire
      distinctive, complementary features that originate different levels of
      antimicrobial capacities and cytotoxicity and different tissue localization and
      lifespan.This review highlights data suggesting the perspective that the
      combination of overlapping and complementary characteristics of the two
      professional phagocytes promotes their cooperative participation as effectors and
      modulators in innate immunity against infection and as orchestrators of adaptive
      immunity. In the concerted activities operating in antimicrobial innate immunity,
      macrophages and neutrophils are not able to replace each other. The common and
      complementary developmental,kinetic, and functional properties of neutrophils and
      macrophages make them the effector arms of a myeloid phagocyte system that groups
      neutrophils with members of the old mononuclear phagocyte system. The use by
      mammals of a system with two dedicated phagocytic cells working cooperatively
      represents an advantageous innate immune attack strategy that allows the
      efficient and safe use of powerful but dangerous microbicidal molecules.This
      crucial strategy is a target of key virulence mechanisms of successful pathogens.

PMID- 20052801
TI  - Pivotal advance: Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded microRNA
      specifically induce IL-6 and IL-10 secretion by macrophages and monocytes.
AB  - Macrophages are an important source of inflammatory cytokines generated during
      the innate immune response,but in the microenvironment of certain
      tumors,macrophages promote tumor progression through their preferential secretion
      of cytokines that support tumor cell growth and suppress antitumoral immune
      responses. KSHV is the causative agent of KS and lymphomas preferentially arising
      in immuno compromised patients, and specific cytokines, including IL-6 and IL-10,
      have been implicated in KSHV-associated cancer pathogenesis. However, the
      contribution of KSHV-infected macrophages to the cytokine milieu within KSHV
      related tumors is unclear. We found that individual KSHV-encoded miRNA induce IL
      6 and IL-10 secretion independently and additively by murine macrophages and
      human myelomonocytic cells. Bioinformatics analysis identified KSHV miRNA binding
      sites formiR-K12-3 and miR-K12-7 within the 3'UTR of the basic region/leucine
      zipper motif transcription factor C/EBPbeta, a known regulator of IL-6 and IL-10
      transcriptional activation.Subsequent immunoblot analyses revealed that miR-K12-3
      and miR-K12-7 preferentially reduce expression of C/EBPbeta p20 (LIP), an isoform
      of C/EBPbeta known to function as a negative transcription regulator. In
      addition,RNA interference specifically targeting LIP induced basal secretion of
      IL-6 and IL-10 by macrophages.Taken together, these data support a role for KSHV
      miRNA in the programming of macrophage cytokine responses in favor of KSHV
      related tumor progression.

PMID- 20052803
TI  - A hundred and fifty years of Gray's Anatomy.

PMID- 20052804
TI  - Acts of Remembrance: the power of memorial and the healing of indigenous
      Australia.
AB  - Hillel Friedland Lecture, Adler Museum of Medicine, Faculty of Health Sciences,
      University of the Witwatersrand, Johannesburg, 16 October 2008.

PMID- 20052805
TI  - The story behind the development of computed tomography.

PMID- 20052806
TI  - Arsenic: a beneficial therapeutic poison - a historical overview.
AB  - Arsenicals have been used since ancient Greek and Roman civilizations and in the
      Far East as part of traditional Chinese medicine. In Western countries, they
      became a therapeutic mainstay for various ailments and malignancies in the 19th
      and early 20th centuries. Fowler's potassium bicarbonate-based solution of
      arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid
      leukaemia until the 1930s. After a decline in the use of arsenic during the mid
      20th century, arsenic trioxide was reintroduced as an anticancer agent after
      reports emerged from China of the success of an arsenic trioxide-containing
      herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic
      trioxide was first purified and used in controlled studies in China in the
      1970s.Subsequently, randomised clinical trials performed in the United States led
      to FDA approval of arsenic trioxide in the treatment of patients with relapsed or
      refractory acute promyelocytic leukaemia.

PMID- 20052807
TI  - New culprits and old threats in infectious diseases: the work of disease
      detectives.
AB  - The A.J. Orenstein Memorial Lecture, Medical School, Univ. of the Witwatersrand,
      Johannesburg, 12 August 2009

PMID- 20052808
TI  - The satisfaction of doing national work, the delight of change and a good salary:
      the health of British colonial nurses going to work in the concentration camps of
      the Anglo-Boer War (1899-1902).
AB  - During the South African/Anglo-Boer War(1899-1902), the British established
      concentration camps in retaliation to Boer guerilla fighters. Thousands of Boer
      women and children and thousands of blacks and "coloured" people were interned
      within these camps. The conditions in the camps were unsanitary and led to the
      death by disease,mostly respiratory illnesses, of many of the inmates. There were
      outcries in Britain over the camps among Liberal members of Parliament and social
      reformers such as Emily Hobhouse. In response to this, the Secretary of War sent
      an all ladies commission to South Africa. Their final report cited unsanitary
      conditions and insufficient camp administration as contributing factors to the
      high death rates.Among their recommendations was to increase the nursing staff.
      The Colonial Nursing Association provided nurses for these jobs. This article
      uses a previously unused archival source, the case notes of the medical advisor
      to the Colonial Office. In 1901-1902, he examined a group of nurses going out to
      work in the concentration camps of South Africa. This article presents the
      results of the examinations of 89 nurses, three of whom were rejected, and places
      them in the context of medical concerns at the time.

PMID- 20052809
TI  - The world's first in vitro fertilisation of a gestational surrogate mother.

PMID- 20052810
TI  - Aspects of mental health nursing.

PMID- 20052812
TI  - Retraction of the article. A transmesenteric hernia in a child: gangrene of a
      long segment of small bowel through a large mesenteric defect.

PMID- 20052811
TI  - [How can we interpret the high prevalence of extrapancreatic neoplasms in
      patients with intraductal papillary mucinous neoplasm of the pancreas?].

PMID- 20052813
TI  - Axillary block by "selective" injections at the nerves involved in surgery using
      a peripheral nerve stimulator: a comparison with a "standard" triple-injection
      technique.
AB  - BACKGROUND AND OBJECTIVES: A triple-injection technique (injections at the
      median, musculocutaneous, and radial nerves) for axillary block affords a high
      incidence of complete block (all the nerves below the elbow). However, in certain
      surgeries, only 1 or 2 nerves are involved in the surgical field. The aim of this
      prospective randomized study was to test the effectiveness of surgical anesthesia
      of a "selective" approach in which only the nerves involved in surgery were
      electrically located and injected. METHODS: Three types of surgery were selected.
      Type 1 included surgery on the fifth finger, type 2 included superficial surgery
      (without bone involvement) on the palm or on the dorsum of the hand, and type 3
      included any surgery on the first 3 fingers. For each type, 138 patients were
      enrolled and divided into 2 groups: group SEL in which only the nerves involved
      in the surgical field (1 or 2) were located and injected and group TNS in which a
      standard triple-nerve stimulation technique was used. RESULTS: A lower rate of
      surgical anesthesia (84% vs 92%; P G 0.05)was recorded in group SEL considered as
      a whole: this was mainly due to the significant difference recorded in type 2
      surgery (75% vs 93%;P G 0.05). More patients needed intravenous administration of
      fentanyl for tourniquet pain (18% vs 8%; P G 0.005) and of midazolam for
      intraoperative anxiety (20% vs 8%; P G 0.005) in group SEL considered as a whole.
      In type 1, improved patient comfort at block performance(P G 0.05), a 7-min
      saving on total anesthetic time (P G 0.001), and a higher need for midazolam
      administration (P G 0.05) were recorded in group SEL. In type 2, a higher need
      for midazolam administration(P G 0.05) was recorded in group SEL. In type 3, no
      clinically significant differences between the groups were recorded. CONCLUSIONS:
      A standard triple-nerve stimulation technique seems to be preferable to the
      selective approach even when a limited number of nerves are involved in the
      surgical field.

PMID- 20052814
TI  - The effect of levosimendan on bupivacaine-induced severe myocardial depression in
      anesthetized pigs.
AB  - BACKGROUND AND OBJECTIVES: Levosimendan, an inodilator without proarrhythmogenic
      properties, has been shown to reverse ropivacaine-induced negative inotropy in
      isolated heart preparations. In this randomized and blinded study, we
      investigated whether levosimendan is able to reverse rapidly bupivacaine-induced
      myocardial depression in pigs. METHODS: Twenty invasively monitored pigs
      anesthetized with isoflurane 1% received bupivacaine 2 mg/kg per minute into a
      central vein until mean arterial pressure decreased to 55% of baseline.
      Thereafter, levosimendan 80 microg/kg for 10 mins, followed by 0.7 microg/kg per
      minute during the next 50 mins (L-SIM) or corresponding amounts of placebo were
      administered intravenously. Simultaneously, Ringer's acetate was infused
      intravenously, 20 mL/kg for 10 mins, followed by 20 mL/kg for 50 mins. RESULTS:
      Two pigs in each group developed cardiac arrest immediately after bupivacaine and
      could not be resuscitated. Bupivacaine induced widening of the QRS complex in the
      electrocardiogram and bradycardia.In the remaining 16 pigs, 3 (2 in L-SIM group
      and 1 in placebo group) needed short-lasting manual cardiac compression and 1
      dose of epinephrine. Cardiac output, ejection fraction, and stroke power/end
      diastolic volume recovered initially very rapidly in the L-SIM group.However,
      there was no time x group effect difference in the overall recovery in the
      various parameters between the 2 groups, except in heart rate which was higher (P
      G 0.05) when levosimendan was administered.During the 50-min levosimendan
      infusion, mean arterial pressure and systemic vascular resistance stayed slightly
      lower in comparison with placebo infusion, but the difference was not
      statistically significant. CONCLUSIONS: Levosimendan together with the infusion
      of Ringer's solution rapidly reversed the cardiac depression, but there was no
      difference in overall cardiovascular recovery in comparison to treatment with
      Ringer's solution alone. Levosimendan-induced increase in heart rate possibly
      facilitated the recovery from bupivacaine intoxication.

PMID- 20052815
TI  - Modeling cost of ultrasound versus nerve stimulator guidance for nerve blocks
      with sensitivity analysis.
AB  - BACKGROUND AND OBJECTIVES: Ultrasound guidance for regional anesthesia has
      increased in popularity. However, the cost of ultrasound versus nerve stimulator
      guidance is controversial, as multiple and varying cost inputs are involved.
      Sensitivity analysis allows modeling of different scenarios and determination of
      the relative importance of each cost input for a given scenario. METHODS: We
      modeled cost per patient of ultrasound versus nerve stimulator using single
      factor sensitivity analysis for 4 different clinical scenarios designed to span
      the expected financial impact of ultrasound guidance. RESULTS: The primary cost
      factors for ultrasound were revenue from billing for ultrasound (85% of variation
      in final cost), number of patients examined per ultrasound machine (10%), and
      block success rate (2.6%). In contrast, the most important input factors for
      nerve stimulator were the success rate of the nerve stimulator block (89%) and
      the amount of liability payout for failed airway due to rescue general anesthesia
      (9%). Depending on clinical scenario, ultrasound was either a profit or cost
      center. CONCLUSIONS: If revenue is generated, then ultrasound-guided blocks
      consistently become a profit center regardless of clinical scenario in our model.
      Without revenue, the clinical scenario dictates the cost of ultrasound. In an
      ambulatory setting, ultrasound is highly competitive with nerve stimulator and
      requires at least a 96% success rate with nerve stimulator before becoming more
      expensive. In a hospitalized scenario, ultrasound is consistently more expensive
      as the uniform use of general anesthesia and hospitalization negate any positive
      cost effects from greater efficiency with ultrasound.

PMID- 20052816
TI  - Regional anesthesia in the patient receiving antithrombotic or thrombolytic
      therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based
      Guidelines (Third Edition).
AB  - The actual incidence of neurologic dysfunction resulting from hemorrhagic
      complications associated with neuraxial blockade is unknown. Although the
      incidence cited in the literature is estimated to be less than 1 in 150,000
      epidural and less than 1 in 220,000 spinal anesthetics, recent epidemiologic
      surveys suggest that the frequency is increasing and may be as high as 1 in 3000
      in some patient populations.Overall, the risk of clinically significant bleeding
      increase with age,associated abnormalities of the spinal cord or vertebral
      column, the presence of an underlying coagulopathy, difficulty during needle
      placement,and an indwelling neuraxial catheter during sustained anticoagulation(
      particularly with standard heparin or low-molecular weight heparin). The need for
      prompt diagnosis and intervention to optimize neurologic outcome is also
      consistently reported. In response to these patient safety issues, the American
      Society of Regional Anesthesia and Pain Medicine (ASRA) convened its Third
      Consensus Conference on Regional Anesthesia and Anticoagulation. Practice
      guidelines or recommendations summarize evidence-based reviews. However, the
      rarity of spinal hematoma defies a prospective randomized study, and there is no
      current laboratory model. As a result,the ASRA consensus statements represent the
      collective experience of recognized experts in the field of neuraxial anesthesia
      and anticoagulation. These are based on case reports, clinical series,
      pharmacology,hematology, and risk factors for surgical bleeding. An understanding
      of the complexity of this issue is essential to patient management.

PMID- 20052817
TI  - [Diagnosing of Acanthamoeba keratitis].
AB  - Acanthamoeba keratitis is rare corneal disease, its etiology is caused by amoebae
      of the Acanthamoeba spp. In this paper, the newest findings about the diagnostic
      and treatment procedures of the disease and epidemiology and preventive issues
      from the point of public health are presented. The article presents results of
      the water quality monitoring (according to the Acanthamoeba which is possible to
      cultivate at 36 degrees C and 44 degrees C) in man-made swimming pools during the
      period 2004-2008 at the Department of environmental biology of the Regional
      Public Health Institute in Banska Bystrica, Slovakia, E.U. The examination
      methods present the techniques of the clinical sampling and taking samples from
      the environment. The results underline the use of the new effective criteria in
      controlling of recreational resorts as well as changes of the legal criteria for
      the water quality used by the public. The results show that the presence of
      Acanthamoeba spp. in the environment is common, so the water monitoring is
      perceived as substantial preventive issue to prevent the disease to emerge. The
      collaboration between the public heath departments and ophthalmologists during
      the examination of the clinical and environmental samples may help to prevent and
      diagnose the Acanthamoeba keratitis.

PMID- 20052818
TI  - [Current therapeutic approach in non-infectious uveitis].
AB  - The aim of this paper is to summarize current therapeutic approach in non
      infectious uveitis. It focuses on different immunosuppressive/immunomodulatory
      treatment modalities and address' its adverse effects.

PMID- 20052819
TI  - [Contrast sensitivity and higher order aberration after conventional LASIK
      treatment].
AB  - AIM: The aim of the prospective study was to evaluate photopic high-contrast
      visual acuity, mesopic contrast sensitivity, and high order aberrations, to
      compare changes and post-operative development of those parameters and to analyze
      the dependence among aberrations and contrast sensitivity after conventional
      LASIK treatment. MATERIALS AND METHODS: The authors followed-up patients treated
      by means of refractive LASIK treatment during the period from November 2006 to
      November 2007. The authors analyzed 51 eyes (31 patients). The average age of the
      group was 28.5 +/- 5.4 years (range, 18 - 41 years), preoperative average
      spherical equivalent was -4.95 +/- 1.24 D (from -3 to -8,25 D). Before the
      treatment and 1, 3, 6, and 12 months after LASIK treatment we evaluated the
      visual acuity (Snellen optotypes), contrast sensitivity under mesopic
      circumstances (CSV-1000E, VectorVision) and monochromatic aberrations (aberometer
      Zywave, Bausch & Lomb). RESULTS: One year after the treatment the average
      uncorrected visual acuity was 1.07 +/- 0.15, index of effectiveness 0.99, and
      index of safety 1.02. The contrast sensitivity was in month 12 significantly
      decreased comparing to the preoperative level at the frequency 12 c/deg, in other
      already tested frequencies after 3-6 moths did not differed from preoperative
      values. During the follow-up period the curvature of contrast sensitivity average
      values was in the upper half of the normal interval range. Conventional LASIK
      treatment significantly induced the higher order aberration (twice), as well as
      the spherical aberration (four times).The same level of higher order aberrations
      root mean square (HOA-RMS), or increased maximally by 0.1 microm was detected by
      10 % of cases; the spherical aberration was, compared to the preoperative value,
      lower, or increased maximally by 0.05 microm in almost one half of the cases. The
      increase of the higher order aberrations depended directly proportionally to the
      preoperative value of the spherical equivalent. Before the treatment, the values
      of total aberrations correlated to the contrast sensitivity of low space
      frequencies; however, there was not found any correlation between the higher
      order aberrations and contrast sensitivity. Six months after the LASIK treatment
      the values of higher order aberrations correlated to the contrast sensitivity
      except of the lowest frequency tested. The higher order aberrations increased
      together with decreasing contrast sensitivity. The data from the one-year follow
      up control did not show statistically significant correlation between the
      contrast sensitivity and the higher order aberrations. There was not found any
      correlation between the contrast sensitivity and the spherical aberration at any
      follow-up control after the surgery. CONCLUSION: Although after the conventional
      LASIK treatment the curve of mesopic contrast sensitivity was located in the
      upper half of the normal range, in the medial space frequency it remained
      decreased comparing to the preoperative stage. The induction of higher order
      aberrations was twice as much and was directly correlated to the degree of the
      laser correction. The spherical aberration was four-times higher comparing to the
      preoperative values and was independent to the level of the initial refractive
      error. Significant correlation between the contrast sensitivity and the higher
      order aberrations was not proven.

PMID- 20052820
TI  - [Changes of higher order aberrations and contrast sensitivity after standard
      photorefractive keratectomy].
AB  - The aim of the prospective study was to evaluate higher order aberrations and
      contrast sensitivity after photorefractive keratectomy (PRK) using the standard
      photoablation profile. MATERIALS AND METHODS: The group consisted of 37 patients
      (69 eyes), the mean age 27.2 +/- 4.5 years, who underwent PRK with target
      emetropia during the period January 2007 -December 2007. In 19 cases, it was
      correction of myopia, in 50 cases myopia with astigmatism.The preoperative
      spherical equivalent was -3.14 +/- 0.95 D. The PRK was performed by means of
      excimer laser system Technolas 217 (Bausch & Lomb) with the standard
      phoptoablation profile (PlanoScan 2000), using the 6.5 mm optical zone. The
      visual acuity, contrast sensitivity (CS; CSV-1000E, VectorVision) under mesopic
      circumstances and monochromatic aberrations (Zywave, Bausch & Lomb) were
      evaluated before the surgery, and 1,3, 6, and 12 months thereafter. The pair t
      test, Wilcoxon test, and the Mann - Whitney U test (alpha = 0.05) were used for
      the statistical analysis. RESULTS: The PRK showed high index of effectiveness and
      safety (0.98, respectively 1.03 in the first year after the procedure). The
      contrast sensitivity under mesopic circumstances was not significantly involved
      after the PRK. The main value of the CS remained during the whole follow-up
      period within the physiological range in all spatial frequencies.
      Postoperatively, the part of spherical aberration on the higher order aberrations
      increased from 13.1% preoperatively to 16.6% one year after the PRK. In one half
      of the cases, the change of the higher order aberrations was within the range +/-
      0.1 microm. In 66% of cases, the change of the spherical aberration was +/- 0.05
      microm. The higher order aberrations comparing to the preoperative values
      decreased or remained unchanged approximately in one third of the cases, and the
      spherical aberration in one quarter of the cases. There was not established
      dependence between monochromatic aberrations values and the contrast sensitivity.
      CONCLUSION: Although the conventional RPK for low myopia treatment induces higher
      order aberrations including the spherical aberration, the impact on the contrast
      sensitivity under mesopic circumstances in our group were not significant. The
      contrast sensitivity of the most of patients was near the upper limit of the
      normal range.

PMID- 20052821
TI  - [Lucentis in treatment of the wet-form of age-related macular degeneration--two
      years experience].
AB  - In a study group of 114 patients (39 males, 75 females) with mean age of 72, 5
      years (from 52 to 89 years) with mean follow-up of 8 month we retrospectively
      studied the effectivity and safety of intravitreal aplication of ranibizumab =
      Lucentis in the case of wet form of age-related macular degeneration (AMD). All
      patients met the inclusion criteria. The treatmet was realized on outpatient
      basis under strict application protocol. In the follow-up period the visual
      acuity improved in 66 patients (57%), stabilization was achieved in 17 patients
      (24.9%). In a group of 31 patients (27.2%) the central acuity deteriorated. There
      were no peroperative complications. In the postoperative period we observed in 22
      patients temporary rise of intraocular pressure, in 21 patients suffusion, and in
      3 patients there were subretinal haemorrhages found, in 1 case rupture of RPE and
      in 1 case anterior ischemic opticopathy was observed. Results observed in this
      study are in full compliance with PRONTO and PIER studies.

PMID- 20052822
TI  - [Combined occlusion of central retinal vein].
AB  - Combined occlusion of central retinal vein and cilioretinal artery represents 40%
      of all cilioretinal artery occlusions. Pathogenesis of this uncommon occlusion
      remains controversial. We present three cases id combined vascular occlusion that
      were diagnosed at our department from 2003 until 2008. Our patients, all
      productive age, had undergone complete clinical examinations and investigations
      to determine the cause of this condition. One patient had been diagnosed to have
      heterozygous form of protrombine mutation. Curious is also possible connection of
      vascular occlusion and application of anti-Hepatitis A and B vaccine.

PMID- 20052823
TI  - [Comparison of the threshold interpolation and whole-line method on logMAR chart
      and Snellen chart for visual acuity testing].
AB  - The main goal of our study was to prove the statistical significant difference
      between the threshold interpolation logMAR method on ETDRS chart and the whole
      line method on Snellen chart with Sloan letters. We had 108 measurements with the
      threshold interpolation method and the whole-line method on ETDRS chart and the
      whole-line method on Snellen chart. The average value measured with the threshold
      method in ETDRS was 1,132 (min. 0,660, max. 1,580), with the whole-line method on
      ETDRS it was 1,134 (min. 0,630, max. 1,580) and with the whole-line method on
      Snellen chart it was 1,183 (min. 0,630, max. 1,600). We have proved statistical
      significant difference between the threshold interpolation method made on ETDRS
      chart and the whole-line method made on Snellen chart (p < 0.001). The values
      measured with the whole-line method on Snellen chart were overvalued. The exact
      and reliable measuring of visual acuity is an important component of further
      examinations (e.g. contrast sensitivity, perimetry, tonometry), which enable us
      to make a correct diagnosis of pathological changes on human eye structures.

PMID- 20052824
TI  - [Benefit of the surgical treatment of the idiopathic intracranial hypertension--a
      case report].
AB  - The patient (woman), 54 years of age, treated for p-ANCA positive vasculitis,
      hypertension, and thyroid gland hypofunction was referred to our Department due
      to the decrease of the visual acuity of her left eye. Since the year 2003, she
      was followed-up in the Department of Neurology due to the idiopathic intracranial
      hypertension (the opening pressure of the intracranial liquid was 480 -500 mm of
      H2O column), treated by acetazolamide tablets (Diluran) 1/2 tablet once daily.
      She was followed-up for the bilateral persistent papilledema by the local
      ophthalmologist. Due to the progression of the visual acuity loss the
      decompression (fenestration) of the optic nerve sheath was performed, and the
      neurosurgeon recommended the lumbo-peritoneal shunting. Adequate indication and
      choice of the surgical treatment helped to stabilize visual functions.

PMID- 20052825
TI  - [Genetic diagnosis law: with many questions into the new year].

PMID- 20052826
TI  - [The pharmaceutical cost of elderly people in private health insurance].
AB  - In this paper the author analyses the prescription of pharmaceuticals for elderly
      private insured persons. Data from eight firms form the basis of the survey. The
      main focus lies in the analysis of the expenditure per capita and the
      distribution of the pharmaceuticals costs. It will illustrate that costs for
      elderly private insured persons will have a great impact on the expenditure for
      the private health insurance companies in the coming years.

PMID- 20052827
TI  - [Is there a link between the mercury release of amalgam fillings and the results
      of psychological questionnaires?].
AB  - Amalgam as a dental filling material shows excellent material property. It is
      fast, easy and economical to implement. Evidence for the release of mercury (Hg)
      from amalgam fillings was given in a number of studies. Mercury release from
      amalgam dental fillings is often claimed to be a possible cause of unspecific
      chronic symptoms such as chronic fatigue, headache and migraine. The present
      study explored relationships between the mercury release from amalgam fillings
      and the results of psychological questionnaires. The urine of 126 men and women
      in the age range of 16 to 76 years was examined. 45 participants did not present
      any amalgam restorations. The mercury released into the urine was measured by
      using cold-vapour AAS. The results of the study show that chronic mercury
      exposure, in the low concentration range, is not linked with chronic subjective
      symptoms.

PMID- 20052828
TI  - [Visualisation methods for etheric formative forces (II)].

PMID- 20052829
TI  - [Analysis of non-confraternity sports accidents in the surgical department of a
      former district hospital during the period of 2 years].
AB  - This epidemiological study analyses all n = 1,659 outpatient and inpatient non
      confraternity sports accidents treated during a 2-year period in a former
      district hospital. The largest share with 40.6% is soccer, followed by cycling
      (15%), general fitness sports (7.6%), outdoor sports (6.5%), winter sports
      (5.5%), and riding (5.2%). Soccer injuries rise steadily until the age of 30. Of
      86 horse riding accidents a total of 68 involved women, but only 18 men (ratio 8
      : 2). 53% of the horse riding accidents among women concern the age group between
      10 and 20 years. 70.6% (79%) of the athletes under (over) 20 years were male,
      29.4% (21%) female (p < 0.05). Topographically the lower extremities represent
      the most affected body region in all sports (runners 84.4%, soccer players
      60.2%). Most accidents occur on a Sunday. The most common diagnosis is contusion,
      most commonly in martial arts (60.8%), followed by horse riding (51%). There is
      an astonishing dominance of soccer accidents given the fact that this study
      records all athletes, not just club athletes, unlike insurance studies. Important
      preventive measures would be a comprehensive biological training prophylaxis and
      the provision of communication of age-specific accident prevention proposals for
      the mainly affected sports.

PMID- 20052830
TI  - [Insurance medicine counseling by the company doctor of the PKV. 2005
      quantitative analysis].

PMID- 20052831
TI  - [Professional care responsibilities with sedated patients].

PMID- 20052832
TI  - [Personal brand thymus extracts].

PMID- 20052833
TI  - [Alternative medicine lymphoma recurrence prevention in the Swiss Specialist
      Clinic for Holistic Medicine and Dentistry].

PMID- 20052835
TI  - [The generalist in the crossroads].

PMID- 20052834
TI  - [NEURO-MED--a "breakthrough in medicine"?].

PMID- 20052836
TI  - [Dizziness in general practice].
AB  - The symptoms of vertigo are frequent complaints. With the anamnestic features and
      the quite long and tiresome clinical examination alone, the general practitioner
      should make the difference between a benign peripheral and a potentially fatal
      central pathology. A good knowledge of the anamnestic and clinical
      particularities and the diagnostic manoeuvres of the main types of vertigo allows
      in about two thirds of the cases to distinguish their origin. If a central origin
      is suspected or if the etiology is uncertain, the patient should be referred to a
      neurologist for further examination and radiological investigations.

PMID- 20052837
TI  - [Physician-pharmacist collaboration: a way to improve the quality of drug
      prescribing].
AB  - The medical prescription is the end-result of a structured process. It is, in
      effect, a medicolegal document that binds the physician who writes it as well as
      the pharmacist who delivers it, with a civil duty of care that is protected by
      penal sanction. Moreover, prescriptions carry important costs, and can be the
      source of errors, especially where there are breakdowns in the continuity of
      patient care. These features underline the importance of the act of
      "prescribing", and the need for ways to improve its quality through increased
      efficiency and safety. The Swiss experience of physicians-pharmacists Quality
      Circles for drug prescription in the community and in the nursing homes,
      represent with the medication review, one method of safeguarding quality
      prescribing.

PMID- 20052838
TI  - [Is atherosclerosis a periodontally-induced disease?].
AB  - Traditional risk factors do not explain all of cases of ischemic cardiovascular
      disease. The literature now identifies periodontal disease, a chronic oral
      infection, as a potential risk factor of atherosclerosis. Three plausible
      biologic pathways have been proposed to explain this link: a direct action of
      periodontal bacteria migrating by bacteriemia, an indirect action by
      inflammation, mediators an immunopathogenic pathway related to heat shock
      proteins. Clinical studies show an increase in the CRP or recirculating specific
      immunoglobulins in presence of advanced periodontal disease. Other interventional
      studies show a reduction in cardiovascular risk factors when intensive
      periodontal therapy is used in patients with advanced periodontal disease.
      Literature therefore confirms a modest link between periodontal and
      cardiovascular diseases even if causality is not confirmed so far.

PMID- 20052839
TI  - [Pregraduate training in ambulatory care: a Swiss perspective].
AB  - The current lack of general practitioners in Switzerland is the result of health
      care policy which aimed in the past years to reduce the number of medical
      students and physicians in private practice. Furthermore, during the past
      decades, the Swiss Medical Schools emphasized on the transmission of medical care
      by specialists and neglected primary care medicine. The Faculty of medicine at
      the University of Lausanne recently decided to renew the curriculum. The
      Department of ambulatory care and community medicine (Policlinique Medicale
      Universitaire) of Lausanne is committed to the elaboration of this move. The
      biomedical model, essential to the acquisition of clinical competence, is still
      taught to the students. Nevertheless, from the beginning to the end of the
      curriculum, an emphasis is now put on the clinical skills and the clinical
      reasoning.

PMID- 20052840
TI  - [Cost-effectiveness analyses: what doctors should know].
AB  - The resources of our heath care system are limited. Choices in the attribution of
      resources are necessary to ensure its stability. A cost-effectiveness analysis
      compares the effects of one health intervention to another, taking into account
      the costs (including the saved costs) and the saved life years, adjusted for the
      quality of life (cost-utility). Cost-effectiveness analyses should take the
      societal perspective and the studied intervention should be compared to a
      relevant intervention actually in use. Physicians, at the interface between
      patients and payers, are in an ideal position to interpret, or even perform cost
      effectiveness analysis, and to promote the interventions that are most effective
      and that have a reasonable cost.

PMID- 20052841
TI  - [What shall I do with a patient with elevated liver tests?].
AB  - In this article you will find a short reminder on the lab tests of the hepatic
      function and of the hepatic diseases. It shall help treat a patient with elevated
      liver tests. We will distinguish between an elevation of the liver enzymes of
      more/equal 5x and less than 5x the norm. An elevation of more/equal 5x the norm
      of the liver enzymes requires a rapid work-up. When the elevation is less than 5x
      the norm, one can proceed in two steps. A life style modification can be proposed
      after excluding a viral hepatitis and a hemochromatosis. If the liver enzymes
      still remind elevated, rarer causes must be searched.

PMID- 20052842
TI  - [Smoking: one drug can hide another].

PMID- 20052844
TI  - [White coat hypertension].

PMID- 20052843
TI  - [Imported cases of histoplasmosis].
AB  - Histoplasmosis is a fungal infection that may be opportunistic in the context of
      HIV. Rare in Europe, it is always imported. The two variants of histoplasmosis
      are encountered in defined geographic areas: var. capsulatum in Americas, Africa
      and Asia; and var duboisii in Africa only. In immuno-competent patients, acute
      infection is often asymptomatic, or it may cause a pulmonary syndrome of variable
      severity. Among immuno-compromised patients, histoplasmosis is disseminated and
      life-threatening. Diagnosis is typically made by cultures. The treatment of the
      disseminated form must be started immediately with anti-fungal therapy and highly
      active anti-retroviral treatment. In a globalized world, one has to remember the
      importation of unusual exotic diseases.

PMID- 20052846
TI  - [The medical Grail has a name: "disability-adjusted life years" (2)].

PMID- 20052845
TI  - [Beautiful hair, beautiful nails-even with aging!].

PMID- 20052847
TI  - [At what point do you stop treatment?].

PMID- 20052848
TI  - [The physician, the patient and death].

PMID- 20052849
TI  - [Vaccination and Guillain-Barre syndrome].

PMID- 20052850
TI  - Systemic lupus erythematosus and pregnancy--a challenge to the clinician.

PMID- 20052851
TI  - Prevalence of antenatal risk conditions among women in an underserved district of
      Northern Sri Lanka.
AB  - OBJECTIVE: To assess the prevalence of risk conditions among antenatal women in
      the Vavuniya District. DESIGN AND SETTING: A cross-sectional study was conducted
      among 392 pregnant women who had completed 36 weeks of gestation and were
      admitted or referred to two leading hospitals in the district. MEASUREMENTS:
      Women were interviewed consecutively using a questionnaire, and their antenatal
      details were extracted from records by trained investigators. Data on socio
      demographics, antenatal care utilisation, risk condition in present and past
      pregnancies, and preexisting illnesses were obtained. RESULTS: Prevalence of an
      antenatal risk condition was 52.0%. The common risk conditions included teenage
      (9.7%) or elderly mother (14.3%), anaemia (8.2%) and abnormal BMI (8.2%). The
      common risk conditions due to past pregnancy were: history of abortion (19.3%),
      past caesarean delivery (8.0%), and stillbirth/neonatal death (4.8%). Less than
      half of the 'at risk' mothers were educated regarding the risk condition (47.5%)
      or referred to (48.5%) by the primary care providers. The majority was advised to
      deliver at a facility with emergency obstetric care. CONCLUSIONS: One in every
      two pregnancies in the Vavuniya District had an antenatal risk condition and
      services should be organised to meet this need.

PMID- 20052852
TI  - Validity of currently used cutoff values of body mass index as a measure of
      obesity in Sri Lankan children.
AB  - OBJECTIVE: The aim of the study was to determine the reliability of body mass
      index based (BMI) cutoff values in diagnosing obesity among Sri Lankan children.
      METHODS: Height, weight, waist circumference (WC) and hip circumference (HC) in
      282 children were measured. Total body water was determined by deuterium dilution
      and fat mass (FM) derived using age and gender specific constants. A percentage
      FM of 30% for girls and 25% for boys were considered as cutoff levels for
      obesity. RESULTS: Two hundred and eighty two children (M/F: 158/124) were studied
      and 99 (80%) girls and 72 (45.5%) boys were obese based on % body fat. Eight
      (6.4%) girls and nine (5.7%) boys were obese based on International Obesity Task
      Force (IOTF) cutoff values. Percentage FM and WC centile charts were able to
      diagnose a significant proportion of children as true obese children. The FM and
      BMI were closely associated in both girls (r = 0.82, p < 0.001) and boys (r =
      0.87, p < 0.001). Percentage FM and BMI had a very low but significant
      association; girls (r = 0.32, p < 0.001) and boys (r = 0.68, p < 0.001). FM had a
      significant association with WC and HC. BMI based cutoff values had a specificity
      of 100% but a very low sensitivity, varying between 8% and 23.6%. CONCLUSIONS:
      BMI is a poor indicator of the percentage fat and the commonly used cutoff values
      were not sensitive to detect cases of childhood obesity in Sri Lankan children.

PMID- 20052853
TI  - Alcohol and tobacco use among males in two districts in Sri Lanka.
AB  - OBJECTIVES: To investigate the prevalence and consumption of tobacco and alcohol
      among males in the Colombo and Polonnaruwa districts. DESIGN: A cross-sectional
      study based on multistage cluster sampling was carried out in four Medical
      Officer of Health (MOH) areas in the Colombo (urban) and Polonnaruwa (rural)
      districts to assess the prevalence of tobacco and alcohol use. The Public Health
      Midwife areas were considered as primary clusters. The sample consisted of males
      over 18 years. There were 1318 from the Colombo District and 1366 from the
      Polonnaruwa District. The quantity frequency method was used to assess
      consumption. RESULTS: Abstinence was significantly higher in the rural areas
      (75.2%) compared to urban areas (56.6%) (p < 0.001). Prevalence of current
      drinking in the urban areas (32.9%) was significantly higher than in rural areas
      (20.8%) (p < 0.001). Alcohol consumption in the urban areas (33.1 units/week) was
      significantly higher than in rural areas (20.9) (p < 0.004). 51.6/1000 males in
      the urban areas and 14.6/1000 males in rural areas consumed daily. The prevalence
      of current smoking was also higher in the urban areas (29.9%) than (p = 0.052) in
      rural areas (24.4%). CONCLUSION: High-risk alcohol consumption was prevalent
      especially in urban areas as indicated by the mean alcohol consumption and number
      who consumed spirits daily. The prevalence of smoking is much lower than in many
      Asian countries but similar to western Europe.

PMID- 20052854
TI  - Selected determinants and sequelae of exclusive breastfeeding up to six months
      among infants attending chosen well baby clinics in the Colombo District.
AB  - OBJECTIVES: To ascertain determinants and impact of the duration of exclusive
      breastfeeding (EBF) for four to six months on growth and incidence of respiratory
      tract and diarrhoeal infections DESIGN AND SETTING: A descriptive cross-sectional
      study of infants aged 4-6 months, visiting selected well baby clinics in Colombo.
      MEASUREMENTS: An interviewer administered questionnaire to determine duration and
      determinants of EBF and incidence of infections was used. Growth faltering was
      ascertained by perusing the growth chart. RESULTS: The EBF rate for 4 months and
      beyond was 52.1% with only 3.6% being exclusively breastfed for 5 months and none
      for 6 months. 61% attending hospital clinics had EBF for 4 or more months as
      compared to 42% at community clinics. Higher level of maternal education, EBF of
      earlier child for longer duration, greater number of antenatal clinic visits,
      hearing the optimal duration of EBF via media, being well instructed on expressed
      breast milk and Caesarean section delivery were positively associated with EBF of
      4 months and beyond. Being underweight for age (< 3rd centile) was significantly
      associated with longer periods of EBF, although growth faltering was not. There
      was no significant association between the duration of EBF and incidence of
      respiratory or diarrhoeal infections. CONCLUSIONS: The EBF rate for 4 months and
      beyond was poor, with field clinics faring worse than hospital clinics.

PMID- 20052855
TI  - Ocular infection with an avian trematode (Philophthalmus sp).

PMID- 20052856
TI  - Pre-operative hydrostatic reduction of intussusception in an adult.

PMID- 20052857
TI  - Oro-genital ulcers with a positive pathergy test in acute myeloid leukaemia.

PMID- 20052858
TI  - A complex suicide.

PMID- 20052859
TI  - Update on contraception--1.

PMID- 20052860
TI  - Margosa (Kohomba) oil induced toxic encephalopathy following home remedy for
      intestinal worms.

PMID- 20052861
TI  - [H1N1: chances and opportunities].

PMID- 20052862
TI  - [High altitude and preexisting lung diseases].
AB  - Today, a growing number of people, some of them suffering from lung diseases,
      travel to high altitude resorts. It is sometimes not easy for the general
      practitioner to adequately counsel these patients. Based on our knowledge of
      physiopathology and clinical studies, the present paper addresses the effects of
      high altitude in patients with preexisting lung diseases and provides
      recommendations in order to optimize the sojourn at high altitude.

PMID- 20052863
TI  - [Early detection and treatment of pulmonary arterial hypertension].
AB  - Pulmonary arterial hypertension (PAH) is a rare clinical condition characterized
      by a progressive increase in pulmonary vascular resistance leading to right heart
      failure. The detection of this disease is limited by the accessibility of
      pulmonary vessels and rough initial symptoms, sometimes consisting only
      exertional dyspnea. In most cases, the patient presents a severe damage with a
      limited life expectancy at the time of diagnosis. This diagnosis, however, can be
      facilitated by the recognition of risk factors for the disease. The challenge of
      this early detection is to allow the establishment of a specific treatment which
      aims to improve the prognosis of patients by limiting the progression of the
      vasculopathy.

PMID- 20052864
TI  - [Opioids and sleep disordered breathing].
AB  - Medical use of chronic opioids has recently increased in Switzerland. Even though
      their effect on daytime vigilance tends to disappear after some time, 70% of
      chronic opioid users will suffer from sleep disordered breathing. Most of them
      will show an ataxic breathing during sleep with mostly central apnea alternating
      with short breathing periods, but long hypopnea may also occur. Treatment with
      continuous positive airway pressure (CPAP) is usually ineffective. More
      sophisticated ventilatory modes such as bilevel ventilation with backup
      respiratory rate or adaptive servoventilation are often required. Older patients
      with concomitant COPD or obstructive sleep apnea are at higher risk of developing
      nocturnal breathing disorders.

PMID- 20052865
TI  - [A lung specialist in ALS care: towards less pessimism].
AB  - Specialized and multidisciplinary care is needed for patients with amyotrophic
      lateral sclerosis (ALS). Respiratory failure secondary to respiratory muscle
      dysfunction, ineffective cough, weight loss and progressive loss of autonomy
      should always be sought and explored. Very few tests are needed to assess a
      patient with ALS: spirometry, blood gases, nocturnal oximetry, cough peak-flow,
      and follow-up of body weight. Patients should be informed clearly as to the
      nature and evolution of ALS, and as to the potential benefits and disadvantages
      associated with each treatment modality in order to be involved in therapeutic
      decisions. This evidence-based review focuses on respiratory care of patients
      with ALS.

PMID- 20052866
TI  - [Diffuse parenchymal lung diseases: clinical-radiological correlation].
AB  - Diffuse parenchymal lung diseases can have various clinical and radiological
      presentations. The high-resolution CT scan has a central role in the diagnostic
      process of an interstitial disease. As a first step in the analysis of such an
      exam, one has to look for the major radiological sign and then to describe it to
      build a differential diagnosis in order to guide the management. The goal of this
      article is to illustrate this approach with examples of diffuse parenchymal lung
      diseases.

PMID- 20052867
TI  - [Non tuberculous mycobacteria pulmonary disease: what's new?].
AB  - The incidence of NTM (non tuberculous mycobacteria) pulmonary disease is
      increasing. The diagnosis must be established in the presence of clinical,
      radiological and microbiological findings. Groups at risk to contract pulmonary
      disease due to NTM are patients with underlying structural lung disease.
      Treatment of NTM is long and requires multiple drugs combinations. Relapses and
      re-infection are not rare. Our understanding in many matters of NTM pulmonary
      disease is incomplete. Further research is necessary in order to understand the
      host's defense mechanisms against NTM, and the factors that influence the
      evolution to lung disease.

PMID- 20052868
TI  - [Aging and becoming vulnerable].
AB  - "The vulnerable are those whose autonomy, dignity and integrity are capable of
      being threatened". Based on this ethical definition of vulnerability, four risk
      factors of vulnerability might be identified among elderly persons, and are
      described in this article: the functional limitation, the loss of autonomy, the
      social precariousness and the restriction of access to medical care. A clinical
      case of elderly abuse is presented to illustrate vulnerability. Finally, some
      recommendations to lower the risk of vulnerability in elderly persons are
      proposed.

PMID- 20052869
TI  - [How to prevent falls among elderly living at home].

PMID- 20052870
TI  - [The window. Painting. Love and loneliness].

PMID- 20052872
TI  - [Gene therapy in the adrenoleukodystrophy].

PMID- 20052871
TI  - [Sagan (Francoise), Blondin, Palfium and writings].

PMID- 20052873
TI  - [Effective treatment for infections of the upper and lower respiratory tract].

PMID- 20052874
TI  - [So close . . . family and decision making].

PMID- 20052875
TI  - [Prevention faces lobbies].

PMID- 20052876
TI  - Far from shovel-ready. Legislation that took weeks to write will wreak havoc for
      years.

PMID- 20052877
TI  - ERP implementation services. In an environment of smaller projects requiring
      specialized skills sets, a few consulting firms have adapted and excelled.

PMID- 20052878
TI  - Can you hear me now? Voice recognition for the EMR has made big strides, and many
      say meaningful use requirements will accelerate adoption.
AB  - CIOs need to closely examine clinician workflow when deciding which form of VR
      (front-end or back-end) to use. Highly paid specialists may not want to do their
      own editing. A strong cable backbone is important for real-time voice
      recognition. Introducing VR in the ambulatory setting can help physicians adopt
      in inpatient settings. A site license makes VR easier for the physician by making
      it available on every computer. At some organizations, physicians can have the
      option of transcriptionists, if they pay for it.

PMID- 20052879
TI  - Wait at your own risk. Relying on a vendor to manage ICD-10 conversion can mean
      being held accountable for lost revenue.
AB  - CIOs must have an ICD-10 conversion strategy in place now, since many systems
      will be impacted. Creating a timeline can help determine whether an organization
      is in good shape. CIOs who have not yet implemented an EMR should consider using
      SNOMED. As ICD-10 approaches, it will be necessary to monitor AR days daily,
      instead of monthly. Organizations need to designate and empower an ICD-10 leader
      and begin staff training efforts early.

PMID- 20052880
TI  - One-on-one with Florence Chang, SVP & CIO, MultiCare Health System. As MultiCare
      rolls out more applications and expands its award-winning EHR system, data
      storage is becoming a high priority. Interview by Kate Huvane Gamble.

PMID- 20052881
TI  - Critical care network. ICU telemedicine can help ease the burden of caring for
      critically ill patients--provided all the right pieces are in place.
AB  - Leading-edge organizations are leveraging ICU telemonitoring to more effectively
      monitor critical care patients at satellite locations from a central hub. While
      little objective data is available to support the efficacy of elCUs, some
      organizations are seeing marked improvements in factors like length of stay,
      which has led to cost savings. Lack of interoperability is a significant barrier
      to successful eICU implementation. It is critical that systems are able to speak
      to each other to enable the flow of data between locations. ClOs need to ensure
      that a proper network is in place to support communications--both audio and video
      -and if necessary, to upgrade the connection. Advanced organizations are
      utilizing eICU functionality to produce reports and sophisticated analysis.

PMID- 20052882
TI  - When every second counts. Cutting-edge hospitals are leveraging telestroke
      programs so neurologists can intervene when a stroke hits.
AB  - Telestroke programs offer an innovative approach to optimizing the care of
      patients presenting with stroke symptoms. ClOs are working with clinician leaders
      to support the remote consults that are at the heart of telestroke programs.
      Telestroke programs can be a "win-win" for all stakeholders involved, especially
      the referring hospitals and teaching facilities.

PMID- 20052883
TI  - Going public with HIEs. With a solid infrastructure and the right people, public
      health organizations stand to benefit from HIEs.

PMID- 20052884
TI  - Got people? With HITECH deadlines looming, CIOs need to ramp up staffing if they
      are to achieve meaningful use certification.
AB  - A severe shortage of IT professionals who can help implement EMR, CPOE, and other
      core clinical technologies could soon emerge across hospitals nationwide. CIOs
      could face staffing challenges both within their organizations, and with regard
      to the vendors and consulting firms they might engage to facilitate
      implementation. Keys to retaining staff include ensuring competitive pay scales,
      creating good career ladders, and getting one's team engaged and excited.

PMID- 20052885
TI  - Resigning right. There's a right way and a wrong way to resign--make sure you
      follow these important suggestions.

PMID- 20052886
TI  - Testing the waters. IBM made a splash by linking up with supply giant Baxter in
      1989. But was the model built for long-term success?

PMID- 20052888
TI  - The bucket list.

PMID- 20052887
TI  - A delicate balance. Nurses have dual roles when the patient is a loved one.

PMID- 20052889
TI  - ANA calls for comprehensive protections against influenza.

PMID- 20052890
TI  - APRN regulatory model continues to advance.

PMID- 20052891
TI  - Taking safe patient handling to the home front.

PMID- 20052892
TI  - ANF scholars make a difference with your help.

PMID- 20052893
TI  - The "New" America Electronic Medical Record (EMR)-design criteria and challenge.
AB  - As you can see from a review of the physician interface, there are many exciting
      potentials that exist for the future of the EMR. None of these will happen unless
      we change the focus of the system design process and start by making the
      physician a key and primary player in this equation. To get a proactive physician
      following is the most important step forward and should be a primary focus for
      the large investments that are planned. We need a company or organization that
      sees the need for a future product that will accomplish these goals. We need
      funding for that process and a prototype development effort to perfect the
      design. We need the construction of a relational database of medicine with a
      professional staff to support its operation. Are there entrepreneurs still out
      there that can see this challenge and are willing to invest in its
      accomplishment? I sure hope so and I would be delighted to hear from you by
      email. Please send your comments and critique to: kqinc@aol.com

PMID- 20052894
TI  - Cholangiocarcinoma--an automated preliminary detection system using MLP.
AB  - Cholangiocarcinoma, cancer of the bile ducts, is often diagnosed via magnetic
      resonance cholangiopancreatography (MRCP). Due to low resolution, noise and
      difficulty is actually seeing the tumor in the images, especially by examining
      only a single image, there has been very little development of automated systems
      for cholangiocarcinoma diagnosis. This paper presents a computer-aided diagnosis
      (CAD) system for the automated preliminary detection of the tumor using a single
      MRCP image. The multi-stage system employs algorithms and techniques that
      correspond to the radiological diagnosis characteristics employed by doctors. A
      popular artificial neural network, the multi-layer perceptron (MLP), is used for
      decision making to differentiate images with cholangiocarcinoma from those
      without. The test results achieved was 94% when differentiating only healthy and
      tumor images, and 88% in a robust multi-disease test where the system had to
      identify the tumor images from a large set of images containing common biliary
      diseases.

PMID- 20052895
TI  - Segment-growing hierarchical model for bile duct detection in MRCP.
AB  - Magnetic resonance cholangiopancreatography (MRCP) is the popular diagnostic
      imaging sequence for the diagnosis and surgery workup for the pancreatobiliary
      system and liver. The technique is relatively noisy and suffers from imaging
      characteristics such as the partial volume effect and varying acquisition
      orientation, making automatic analysis of the images difficult. This paper
      explores some of the popular image processing techniques with the goal of
      selecting suitable features in MRCP images, as a basis for preliminary computer
      aided diagnosis systems in biliary structure image reconstruction and disease
      detection. Visual results and observations are given and analyzed. The findings
      support that many popular techniques such as texture analysis fail to highlight
      the structures of interest in MRCP images, whereas multi-scale, multi-resolution
      and dynamic thresholding achieve better success. The proposed multi-scale
      combination technique known as the Segment-Growing Hierarchical Model produced
      good visual results for detection of the bile ducts.

PMID- 20052896
TI  - A new approach to detection of ECG arrhythmias: complex discrete wavelet
      transform based complex valued artificial neural network.
AB  - This paper presents the new automated detection method for electrocardiogram
      (ECG) arrhythmias. The detection system is implemented with integration of
      complex valued feature extraction and classification parts. In feature extraction
      phase of proposed method, the feature values for each arrhythmia are extracted
      using complex discrete wavelet transform (CWT). The aim of using CWT is to
      compress data and to reduce training time of network without decreasing accuracy
      rate. Obtained complex valued features are used as input to the complex valued
      artificial neural network (CVANN) for classification of ECG arrhythmias. Ten
      types of the ECG arrhythmias used in this study were selected from MIT-BIH ECG
      Arrhythmias Database. Two different classification tasks were performed by the
      proposed method. In first classification task (CT-1), whether CWT-CVANN can
      distinguish ECG arrhythmia from normal sinus rhythm was examined one by one. For
      this purpose, nine classifiers were improved and executed in CT-1. Second
      classification task (CT-2) was to recognize ten different ECG arrhythmias by one
      complex valued classifier with ten outputs. Training and test sets were formed by
      mixing the arrhythmias in a certain order. Accuracy rates were obtained as 99.8%
      (averaged) and 99.2% for the first and second classification tasks, respectively.
      All arrhythmias in training and test phases were classified correctly for both of
      the classification tasks.

PMID- 20052897
TI  - Medical diagnosis using adaptive perceptive particle swarm optimization and its
      hardware realization using field programmable gate array.
AB  - The paper proposes to develop a field programmable gate array (FPGA) based low
      cost, low power and high speed novel diagnostic system that can detect in absence
      of the physician the approaching critical condition of a patient at an early
      stage and is thus suitable for diagnosis of patients in the rural areas of
      developing countries where availability of physicians and availability of power
      is really scarce. The diagnostic system could be installed in health care centres
      of rural areas where patients can register themselves for periodic diagnoses and
      thereby detect potential health hazards at an early stage. Multiple
      pathophysiological parameters with different weights are involved in diagnosing a
      particular disease. A novel variation of particle swarm optimization called as
      adaptive perceptive particle swarm optimization has been proposed to determine
      the optimal weights of these pathophysiological parameters for a more accurate
      diagnosis. The FPGA based smart system has been applied for early detection of
      renal criticality of patients. For renal diagnosis, body mass index, glucose,
      urea, creatinine, systolic and diastolic blood pressures have been considered as
      pathophysiological parameters. The detection of approaching critical condition of
      a patient by the instrument has also been validated with the standard Cockford
      Gault Equation to verify whether the patient is really approaching a critical
      condition or not. Using Bayesian analysis on the population of 80 patients under
      study an accuracy of up to 97.5% in renal diagnosis has been obtained.

PMID- 20052898
TI  - A RFID grouping proof protocol for medication safety of inpatient.
AB  - In order to provide enhanced medication safety for inpatients, the medical
      mechanism which adopts the modified grouping proof protocol is proposed in this
      paper. By using the grouping proof protocol, the medical staffs could confirm the
      authentication and integrity of a group of Radio-Frequency Identification (RFID)
      tags which are embedded on inpatient bracelets and the containers of drugs. This
      mechanism is designed to be compatible with EPCglobal Class-1 Generation-2
      standard which is the most popular specification of RFID tags. Due to the light
      weight computational capacity of passive tags, only the pseudo-random number
      generator (PRNG) and cyclic redundancy code (CRC) are allowed to be used in the
      communication protocol. Furthermore, a practical scenario of using this proposed
      mechanism in hospital to examine the medication safety is also presented.

PMID- 20052899
TI  - Cooperative remote video consultation on demand for e-patients.
AB  - With the advent of high-speed internet band-width consuming video conferencing
      applications will rapidly become attractive to e-patients seeking real-time video
      consultations from e-doctors. In a conventional system patients connect to a
      known server in a medical center of his choice. If the server (i.e. a server via
      which a medical consultant communicates with a patient) is busy, the patient must
      wait before the server becomes free. Such a system is not efficient as many
      patients in medical centers with busy servers may either have to wait long, or
      are simply turned away. Patients may also leave when they become impatient. Not
      only the patients suffer due to server unavailability, medical service providers
      also incur revenue losses due to lost patients. To counter these problems, we
      propose a distributed cooperative Video Consultation on Demand (VCoD) system
      where servers are located in many different medical centers in different
      neighbourhoods close to patient concentrations. In such a cooperative system if
      patients find their nearby servers under heavy load they are automatically
      directed to servers that are least loaded by using efficient server selection
      method (also called anycasting). Simple numerical analysis shows that this not
      only maximizes revenues for medical service providers by reducing number of lost
      patients, but also improves average response time for e-patients.

PMID- 20052900
TI  - A comparative study on chronic obstructive pulmonary and pneumonia diseases
      diagnosis using neural networks and artificial immune system.
AB  - Millions of people are diagnosed every year with a chest disease in the world.
      Chronic obstructive pulmonary and pneumonia diseases are two of the most
      important chest diseases. And these are very common illnesses in Turkey. In this
      paper, a comparative study on chronic obstructive pulmonary and pneumonia
      diseases diagnosis was realized by using neural networks and artificial immune
      systems. For this purpose, three different neural networks structures and one
      artificial immune system were used. Used neural network structures in this study
      were multilayer, probabilistic, and learning vector quantization neural networks.
      The results of the study were compared with the results of the pervious similar
      studies reported focusing on chronic obstructive pulmonary and pneumonia diseases
      diagnosis. The chronic obstructive pulmonary and pneumonia diseases dataset were
      prepared from a chest diseases hospital's database using patient's epicrisis
      reports.

PMID- 20052901
TI  - Machine learning in biomedicine and bioinformatics.

PMID- 20052902
TI  - Biomarker identification by knowledge-driven multilevel ICA and motif analysis.
AB  - Traditional statistical methods often fail to identify biologically meaningful
      biomarkers from expression data alone. In this paper, we develop a novel
      strategy, namely knowledge-driven multi-level Independent Component Analysis
      (ICA), to infer regulatory signals and identify biomarkers based on clustering
      results and partial prior knowledge. A statistical test is designed to evaluate
      significance of transcription factor enrichment for extracted gene set based on
      motif information. The experimental results on an Rsf-1 (HBXAP) induced
      microarray data set show that our method can successfully extract biologically
      meaningful biomarkers related to ovarian cancer compared to other gene selection
      methods with or without prior knowledge.

PMID- 20052903
TI  - Logistic ensembles of Random Spherical Linear Oracles for microarray
      classification.
AB  - Random Spherical Linear Oracles (RSLO) for DNA microarray gene expression data
      are proposed for classifier fusion. RSLO employs random hyperplane splits of
      samples in the principal component score space based on the first three principal
      components (X, Y, Z) of the input feature set. Hyperplane splits are used to
      assign training(testing) samples to separate logistic regression mini
      classifiers, which increases the diversity of voting results since errors are not
      shared across mini-classifiers. We recommend use of RSLO with 3-4 10-fold CV and
      re-partitioning samples randomly every ten iterations prior to each 10-fold CV.
      This equates to a total of 30-40 iterations.

PMID- 20052904
TI  - Gene identification and survival prediction with Lp Cox regression and novel
      similarity measure.
AB  - In this paper, Cox's proportional hazards model with Lp penalty method is
      developed for simultaneous gene selection and survival prediction. Lp penalty
      shrinks coefficients and produces some coefficients that are exactly zero, and
      therefore can be used to identify survival related downstream genes. We also
      define a novel similarity measure to hunt the regulatory genes that their gene
      expression changes may be low but they are highly correlated with the selected
      genes. Experimental results with gene expression data demonstrate that the
      proposed procedures can be used for identifying important gene clusters that are
      related to time to death due to cancer and for building parsimonious model for
      predicting the survival of future patients.

PMID- 20052905
TI  - An analysis pipeline for the inference of protein-protein interaction networks.
AB  - We present a platform for the reconstruction of protein-protein interaction
      networks inferred from Mass Spectrometry (MS) bait-prey data. The Software
      Environment for Biological Network Inference (SEBINI), an environment for the
      deployment of network inference algorithms that use high-throughput data, forms
      the platform core. Among the many algorithms available in SEBINI is the Bayesian
      Estimator of Probabilities of Protein-Protein Associations (BEPro3) algorithm,
      which is used to infer interaction networks from such MS affinity isolation data.
      Also, the pipeline incorporates the Collective Analysis of Biological Interaction
      Networks (CABIN) software. We have thus created a structured workflow for protein
      protein network inference and supplemental analysis.

PMID- 20052906
TI  - A technique to search for functional similarities in protein-protein interaction
      networks.
AB  - We describe a method to search for similarities across protein-protein
      interaction networks of different organisms. The technique core consists in
      computing a maximum weight matching of bipartite graphs resulting from comparing
      the neighbourhoods of proteins belonging to different networks. Both quantitative
      and reliability information are exploited. We tested the method on the networks
      of S. cerevisiae, D. melanogaster and C. elegans. The experiments showed that the
      technique is able to detect functional orthologs when the sole sequence
      similarity does not prove itself sufficient. They also demonstrated the
      capability of our approach in discovering common biological processes involving
      uncharacterised proteins.

PMID- 20052907
TI  - Refinement of under-determined loops of Human Prion Protein by database-derived
      distance constraints.
AB  - Due to insufficient experimental restraints, a biologically critical loop region
      in PrP(c) (residues 167-171), which is a potential binding site for Protein X, is
      under-determined in most mammalian species. Here, we show that by adding
      information about distance constraints derived from a database of high-resolution
      protein structures, this under-determined loop as well as other secondary
      structural elements of the E200K variant of Human Prion Protein (hPrP(c)), a
      disease-related isoform, can be refined into more realistic structures in the
      structural ensemble with improved quality and increased accuracy. In particular,
      the ensemble becomes more compact after the refinement and the percentage of
      residues in the most favourable region of the Ramachandran diagram is increased
      to about 90% in the refined structures from the 80% to 85% range in the
      previously reported structures.

PMID- 20052908
TI  - PRTAD: a database for protein residue torsion angle distributions.
AB  - PRTAD is a dedicated database and structural bioinformatics system for protein
      analysis and modelling. The database is developed to host and analyse the
      statistical data for protein residue level 'virtual' bond and torsion angles
      obtained from their distributions in databases of known protein structures such
      as in the PDB Data Bank. PRTAD is capable of generating, caching, and displaying
      the statistical distributions of the angles of various types. The collected
      information can be used to extract geometric restraints or define statistical
      potentials for protein structure determination. PRTAD is supported with a
      friendly designed web interface so that users can easily specify the angle types,
      and retrieve, visualise, or download the distributions of the angles as they
      desire.

PMID- 20052909
TI  - [Design of a novel chimeric protein construction for hydrolysis of beta
      galactosides].

PMID- 20052910
TI  - [Biosynthesis of L-lysine-alpha-oxidase, an antitumor enzyme, by Trichoderma
      spp].
AB  - Strains of Trichoderma spp., producing L-lysine-alpha-oxidase, prospective in
      chemotherapy of malignant tumors, were studied. The best results of the enzyme
      biosynthesis were observed on the wheat bran medium. When grown on the media with
      various pH levels, the strains showed different spectra of the L-aminooxidase
      activity. The highest activity of the strains was recorded with respect to
      destruction of L-lysine. The lysine-producing organism Brevibacterium sp. induced
      L-lysine-alpha-oxidase activity in Trichoderma spp.

PMID- 20052911
TI  - [Activity of supra (e)-dependent dehydrogenases of Staphylococcus epidermidis
      strains susceptible to cefotaxime].
AB  - Investigation of the activity of supra- and supra (e)-dependent dehydrogenases of
      the Staphylococcus epidermidis strains isolated from the pharynx mucous membrane
      of healthy subjects showed that the level of the substrate exchange between the
      tricarbonic acid cycle and the amino acid metabolism reactions, as well as the
      intensity of the glycolysis terminal reactions and the glutathione reductase
      activity depended on the bacteria susceptibility to cefotaxime.

PMID- 20052912
TI  - [New betulin derivatives in combination with rimantadine for inhibition of
      influenza virus reproduction].
AB  - The preliminary studies mainly revealed comparable inhibition activities of 3
      oxime of betulonic acid, 3beta-O-acetyl-28-O-hemiphthalate of betulin and 3,28
      dioxime of betulin against reproduction of influenza viruses A (H1N1), A (H7N1),
      A (H3N2) and B, as well as against the strains of influenza virus A (H1N1) with
      intrinsic resistance to rimantadine and A (H7N1) with acquired resistance to the
      drug. The level of the activity depended on the system used for the virus
      reproduction. The highest level was observed under conditions providing higher
      permissibivity, i.e. in the chick embryo fibroblast cell culture for A (H7N1) and
      in fragments of chick embryo chorioallantoic membranes (for all the viruses). In
      the experiments with virus A/FPV/Rostock/34 (H7N1) in the chick embryo fibroblast
      cell culture the average effective concentrations (EC50) of the triterpene
      compounds were 10.4-17.5 mcM in comparison to EC50 of rimantadine (0.014 mcM).
      The use of every of the compounds in combination with rimantadine resulted in a 2
      16 times decrease of their EC50 and correction of the concentration-effect
      relation of rimantadine. However, when rimantadine was used alone within the
      higher range of the nontoxic concentrations (11.6-57.6 mcM). its antiviral
      properties were significantly less pronounced. As a result the virus titer
      difference in comparison to the control within the above range of the rimantadine
      concentrations increased from < 1 to > 2.35 Ig PPU/ml and the relations of the
      maximal tolerance concentrations of the compounds to their EC50 increased 1.7
      15.9 times.

PMID- 20052913
TI  - [Characterization of batumin resistant variants of Staphylococcus aureus clinical
      isolates].
AB  - Population analysis of 20 batumin susceptible staphylococcal strains, isolated
      from clinical materials allowed to detect resistant clones only in 3 strains. The
      frequency of batumin resistant variants isolation was low and depended on the
      antibiotic concentration. Resistance to batumin in 5 clinical strains and in 1
      reference strain of Staphylococcus aureus ATCC 6538 P (209P) developed under
      laboratory conditions and induced significant phenotypic and chemotaxonomic
      changes in the pathogen. The variants, resistant to batumin, had the same degree
      of virulence for mice as the initial susceptible strain. The batumin resistant
      variants of S. aureus were unstable and on the medium without batumin completely
      restored their initial phenotype.

PMID- 20052914
TI  - [Impact of liposomes and ceftriaxone-entrapped liposomes on skin wound healing in
      rats].
AB  - "Empty" liposomes and ceftriaxone (CT)-entrapped liposomes were developed. Lipids
      of natural origin, i. e. soybean phosphatidyl choline (PhCh) and cholesterol were
      used for the design. The conditions for production of the CT-entrapped liposomes
      were optimized to provide the maximum content of the antibiotic in the liposomes.
      The effect of the "empty" liposomes and the antibiotic-entrapped liposomes on
      healing of skin wounds was studied on rats. The wound on the skin surface of the
      rat back was purulent due to contamination with E. coli (10(9) cells/ml). The
      treatment with the antibiotic solution, "empty" liposomes or CT-entrapped
      liposomes was started in 48 hours. The use of the PhCh "empty" liposomes promoted
      more rapid healing of the wound vs. the control or the treatment with CT aqueous
      solution. The treatmen of the wound with the CT-entrapped PhCh liposomes provided
      2 times more rapid healing vs. the control or the use of the CT aqueous solution.

PMID- 20052915
TI  - [Protective activity of panavir in experimental rabies infection].
AB  - Significant and reliable activity of panavir was shown in experiments on mice
      intramuscularly infected with the rabies virus. The animal protection depended on
      the dose of panavir and the treatment scheme. The reliable protection (30-45% of
      the mice, p<0.05-0.01) was observed only after the panavir intramuscular
      injection to the site of the virus inoculation (the infection atrium), but not
      after the systemic (intraperitoneal) administration. High titers of the virus
      neutralizing antibodies (7.92-10.45 IU/ml), comparable to the antibody titers in
      the combined suspensions of the brain tissues (6.01-10.45% IU/ml), were detected
      in the combined sera of the survived animals treated with panavir. For the first
      time a quantitative method for determination of the virus-neutralizing antibody
      levels in IU/ml was used (the FAVN test, the gold standard for comparative
      evaluation of the level of the vaccinal and infective antirabies immunity).

PMID- 20052916
TI  - [Efficacy of levofloxacin, lomefloxacin and moxifloxacin vs. other
      fluoroquinolones in experimental plague due to FI+ and FI- strains of Yersinia
      pestis in Albino mice].
AB  - Activity of levofloxacin, lomefloxacin and moxifloxacin against 20 FI+ and 20 FI-
      strains of Yersinia pestis was studied. It was shown that the strains were highly
      susceptible to the fluoroquinolones. In the experiments on mice subcutaneously
      infected with suspension of strains 231 FI+ and 231 FI- of Y. pestis in a dose of
      about 1000 LD50 (10(4) microbial cells) the ED50 of levofloxacin and moxifloxacin
      was 5.5-14.0 mg/kg independent of the infective culture phenotype and that of
      lomefloxacin was 18.5 mg/kg. Estimation of the impact of the pathogen infective
      dose value on the results of the experimental plague treatment with the
      therapeutic dose equivalent to the human one showed high efficacy of the
      fluoroquinolones (efficacy index of 10(4)). The treatment for 7 days provided 90
      100-percent survival of the animals. The prophylactive use of lomefloxacin (in 5
      hours - 5 days) was less efficient (70-80% of the survivals) in the animals
      infected with the antigen-changed (FI-) variant of the pathogen. Levofloxacin and
      moxifloxacin provided 90-100-percent survival of the animals treated for a course
      of 5 days independent of the pathogen phenotype. The study demonstrated that the
      use oflevofloxacin, lomefloxacin and moxifloxacin was prospective for the
      prophylaxis and therapy of experimental plague.

PMID- 20052917
TI  - [Investigation of susceptibility of influenza viruses A (H1N1), the cause of
      infection in humans in April-May 2009, to antivirals in MDCK cell culture].
AB  - Biological properties of influenza viruses A (H1N1), that were the cause of the
      infection in humans in April - May 2009, and the action of the Russian antivirals
      on their reproduction were studied in vitro. The nucleotide sequence in the
      viruses was determined and followed by detection of the mutations responsible for
      resistance to the antiinfluenza drugs. The experiments showned that arbidol and
      ribavirin had a selective inhibitory action on reproduction of the viruses in the
      MDCK cell culture while rimantadine had no affect on their reproduction. The data
      were confirmed by the results of the genome analysis in influenza viruses
      A/California/04/2009(H1N1), A/California/07/2009(H1N1) and
      A/Moscow/01/2009(H1N1)swl, that revealed no replacements defining the resistance
      to arbidol while the viruses contained a mutation in position 31 of M2 protein,
      responsible for the resistance to adamantans.

PMID- 20052918
TI  - [Type 1 and type 2 interferon inductor (cycloferon) in therapy of children with
      pyelonephritis associated with herpes viruses].
AB  - The clinical and laboratory efficacy of the treatment of children with
      pyelonephritis with addition of cycloferon, an inductor of early interferon of
      types 1 and 2, to the main therapy was studied. The mechanism of the cycloferon
      action was described. The clinical and laboratory remission within a year was
      observed in 64.3% of the patients treated with addition of cycloferon vs. 47.1%
      of the patients under the main therapy without the cycloferon addition. The
      number of the relapses lowered to 7.1% vs. 20.6% of the episodes in the control
      group. The minimal risk of the disease exacerbation (0.37) in the patients
      treated with cycloferon and the relative risk of the unfavourable outcomes among
      the patients under the therapy with addition of cycloferon (0.5967< or =1) were
      determined.

PMID- 20052919
TI  - [Viferon suppositoria in therapy of relapsing herpesvirus infection in women].
AB  - The therapeutic efficacy of Viferon, a recombinant human interferon alpha-2b
      (rectal suppositoria) was studied in the therapy of relapsing herpesvirus
      infection in women. The clinical efficacy of the drug was recorded in 90% of the
      patients. The analysis of the remote results of the treatment made it possible to
      conclude that the Viferon suppositoria had an antirelapsing activity.

PMID- 20052920
TI  - [Infective endocarditis of staphylococcal etiology: clinical process and
      antibacterial therapy].
AB  - Characteristics of the clinical process of staphylococcal endocarditis in 115
      inpatients and the adequacy of various regimens for their antibiotic therapy
      within a period of 10 years were analysed. Four clinical criteria for prognosis
      of staphylococcal endocarditis were determined: intravenous narcomania,
      splenomegalia, leukocytosis and hemorrhagic skin eruption. The analysis of the
      Russian and foreign findings showed that the use of betalactams (oxacillin, the
      1st and 3rd generation cephalosporins) and lincomycin provided the adequate
      therapy resulting in eradication of the pathogen in case of oxacillin resistant
      staphylococci, whereas the use of ciprofloxacin and vancomycin was inexpedient.
      In case of MRSA it was recommended to use vancomycin and in case of endocarditis
      due to S. aureus with intermediate resistance to vancomycin (VISA, MIC > 0.5
      mcg/ml) the use of linezolid was recommended.

PMID- 20052921
TI  - [Antibiotic therapy of mild community-acquired pneumonia in inpatients].
AB  - From the clinicoeconomic viewpoints the treatment of community-acquired pneumonia
      in patients without risk factors under hospital conditions with aminopenicillins
      was more appropriate, whereas for the treatment of patients with risk factors the
      following scheme of antibiotic therapy was advantageous: a beta-lactam
      (cefotaxime/ceftriaxone) in combination with a macrolide (azithromycin). The
      recommended therapy provided statistically lower percentage of negative pneumonia
      processes and decreased the treatment expenditures.

PMID- 20052922
TI  - [Modulation of nuclear receptor action and regulation of medicines
      biotransformation].
AB  - Nuclear receptors are transcription factors that are essential in embryonic
      development, cellular differentiation, metabolism. Ligand-regulated nuclear PXR
      receptor responds to diverse arrays of chemically distinct ligands, xenobiotics,
      drugs and regulates expression of the genes involved in xenobiotic and drug
      metabolism. The structural basis of the receptor provides interaction with a
      variety of ligands which are agonists or antagonists. Nuclear receptors
      researches are important for design of metabolism regulating drugs and in drug
      interaction studies.

PMID- 20052923
TI  - [Prospects in surgery--88 years since the journal launch and the 40-year work of
      Prof. MUDr Milos Hajek, DrSc].

PMID- 20052924
TI  - [Transmyocardial laser revascularization].
AB  - AIM OF THE STUDY: The study looked at our results with transmyocardial laser
      revascularization. We also tried to ascertain the role of TMLR in current
      cardiothoracic surgical practice. METHODS: Twenty patients underwent TMLR at IKEM
      Praha in a period from 1999 to 2007. Patients were categorized into two separate
      groups. The first included patients who had TMLR as a single procedure. Second
      group comprised patients who underwent combined TMLR and direct bypass
      revascularization. Outcome measures were reduction of angina, improvements in
      exercise tolerance and left ventricular systolic function. RESULTS: Improvement
      in CCS classification of two and more classes has been achieved in almost half
      the patients who underwent TMLR combined with CABG, but only in 20% of patients
      after isolated TMLR. There was no change in left ventricular systolic function
      either in group of patients after TMLR or in group with hybrid procedure. There
      was also no change detected in myocardial perfusion in thallium scintigraphy
      studies. CONCLUSION: The study confirmed that TMLR has minimal perioperative
      complication rate and is safe. On the other hand our results failed to
      demonstrate any significant improvement in quality of life following TMLR. In our
      opinion TMLR should be reserved for symptomatic patients in CCS IV class when all
      other conventional treatment options have been exhausted.

PMID- 20052925
TI  - [Replacement of aortic valva and ascending aorta in patient with Takayasu's
      arteritis].
AB  - Takayasu's arteritis (TA) is a rare vascular disorder, which predominantlly
      affects aorta and its primary branches. TA has a worldwide distribution and it is
      most frequent in young women. We report the case report of 36-year-old women, who
      underwent replacement of aortic valve and ascending aorta due to signifiant
      aortic regurgitation and dilatation of ascending aorta as a consequence of TA.

PMID- 20052926
TI  - [Compressive syndromes of the suprascapular nerve--experience with surgery].
AB  - Compression of suprascapular nerve at the suprascapular notch or spinoglenoid
      notch can be a cause of a rare mononeuropathy. Patients complain of pain in
      scapula and shoulder, and selective wasting and weakness of the supraspinatus and
      infraspinatus muscles. Tenderness at the suprascapular notch and pain by forced
      abduction of arm are typical and useful signs. Electromyographic signs of various
      grade denervation are regularly found in both muscles. Development of entrapment
      syndromes is associated with chronic overload, shoulder injuries, with surgical
      procedures, or with shoulder-arm fixation. The authors present their own group of
      10 patients, who were operated on for entrapment syndrome of suprascapular nerve
      during 7 year period. Direct or indirect traumatic mechanisms of development of
      nerve compression were disclosed in most patients. During postoperative period
      there was not only substantial decrease of pain, but also regression of weakness
      and wasting of both muscles. In discussion, necessity of differential diagnostic
      procedures in case of pain and muscle wasting, use of appropriate imaging
      techniques, demand of purposeful EMG examination, and postoperative follow-ups
      are emphasized.

PMID- 20052927
TI  - [Antimicrobial treatment of nosocomial intra-abdominal infections--new treatment
      options with tygecycline].
AB  - INTRODUCTION: Nosocomial, intra-abdominal infections are extremely serious
      conditions, considering possibilities for their early diagnosis, as well as for
      their effective therapy. Multiresistant bacteria (Enterobacteriacae producing
      extended-spectrum beta-lactamases - ESBL Escherichia coli, Klebsiella species,
      vancomycin-resistant enterococci [VRE], and methicillin-resistant Staphylococcus
      aureus [MRSA]) are frequently isolated as pathogens of these infections.
      Tygecycline is among the novel wide- spectrum antibiotics affecting
      multiresistant bacteria, which are being introduced in clinical practice. AIM:
      The aim of this study is to assess actual sensitivity of tygecycline to the
      commonest pathogens of intra-abdominal infections, generated in hospitalized
      surgical patients. Based on the sensitivity tests, tygecycline was indicated for
      targeted antibiotic therapy in intraabdominal infections. METHODS: Sensitivity to
      tygecycline, aminopenicillins, fluorochinoloni and gentamycine was established
      for the following bacteria: Escherichia coli, Klebsiella pneumonie, Enterobacter
      cloacea, Proteus mirabilis. Sensitivity to oxacillin, clincamycine and
      tygecycline was tested in Staphylococcus aureus, and to fluorochinolini,
      gentamycine and tygecycline in Enterococcus faecalis, and to fluorochinoloni,
      gentamycine, ceftazidime and gentamycine in Pseudomonas aeruginosa. Based on the
      sensitivity results, tygecycline was administered in two patients with
      postsurgical intra-abdominal infections caused by ESBL Escherichia coli and
      Klebsiella pneumonie. The initital dose of tygecycline was 100 mg i.v., followed
      by tygecycline 50 mg i.v. every 12 hours for 7 days. RESULTS: The isolated
      bacteria showed 98-100% sensitivity to tygecycline, except Psudomonas aeruginosa,
      where 100% resistance was demonstrated. Targeted antimicrobial medication with
      tygecycline proved effective in postoperative nosocomial intra-abdominal
      infections, the both concerned patients recovered. CONCLUSION: The choice of
      antimicrobial medication in nosocomial intra-abdominal infections requires
      through evaluation considering various factors including prior antibiotic
      therapy, co-morbidities and the current status of sensitivity with respect to
      potential multiresistant pathogens. Tygecycline shows significant in vitro
      efficacy against resistant gram-positive and key gram-negative facultative
      bacteria, which are a common cause of intra-abdominal infections in surgery
      patients. Clinical experience has shown that tygecycline is safe and effective in
      the treatment of complicated intra-abdominal infections.

PMID- 20052928
TI  - [Laparoscopic liver resections. Successes and failures associated with the
      technique introduction--case reports].
AB  - The authors present initial clinical experience with laparoscopic liver
      resections as a case report series. The operation time, hospital and ICU stay
      length, perioperative blood loss, transfusion units used, and postoperative
      complications were recorded in a prospective way. The reasons for conversion to
      open surgery were also evaluated. 15 laparoscopic liver resections were completed
      between May 2006 and February 2009. There were 11 anatomical resections including
      hemihepatectomies and 4 non-anatomical laparoscopicaly completed liver
      resections. The initial experience shows that laparoscopic liver resection is
      feasible and safesate approach that requires advances experience in laparoscopic
      operative technique and liver surgery. Introduction of the laparoscopic technique
      is not easy and is associated with high risk of hilar bile duct injuries and
      perioperative bleeding.

PMID- 20052929
TI  - [Laparoscopic adrenalectomy].
AB  - OBJECTIVE: Laparoscopy has become the gold standard for the treatment of adrenal
      tumours in urology. We evaluate our experience with laparoscopic adrenalectomy
      (LA) in this work. MATERIAL, METHODS: We performed 38 LA between 2003-2008. We
      use computer tomography (CT) and magnetic resonance imaging (MRI) for the initial
      evaluation. Indication for procedure is made in cooperation with endocrinologist.
      We use transperitoneal approach with 3 or 5 ports. RESULTS: Mean age was 57.7 +/-
      11.7 year (range 32-74.9 year). Nine LA were made in men (24%), in women 29
      (76%). Sixteen tumours (42%) were hormonal active (7 pheochromocytoma, 6 primary
      hyperaldosteronism, 3 peripheral hypercortisolism). Twenty-two tumours were
      without hormonal activity. Mean tumour size was 4.1 +/- 2 cm (range 1-10.1 cm),
      mean operation time was 89 +/- 38 minutes (range 32-220 minutes), mean blood loss
      was 33 +/- 75 ml (range 0-400 ml), mean hospitalization time was 6.1 days (range
      3-12 days). There were histologically 15 cortical adenomas, 5 nodular cortical
      hyperplasia, 1 calcificated hematoma, 3 cysts, 2 potentional malignant tumours on
      interface between adenoma and carcinoma, 1 cortical carcinoma and 7
      pheochromocytoma. We found 3 metastases of renal carcinoma in adrenal gland and
      one metastasis mesenchymal chondrosarcoma too. Transperitoneal approach was
      chosen in 20 patients (53%) after previous abdominal operation (open
      cholecystectomy, appendectomy, transperitoneal nephrectomy, aortofemoral bypass).
      Complications were in 3 cases from 38 (8%). It was one perforation of diaphragm,
      which was resolve with laparoscopic suture, one postoperative delirium with fudge
      and agitation, one abscess in wound after extraction of specimen. We have got any
      conversion in our collection. The body mass index was higher than 38 in 3
      patients. CONCLUSION: LA is a quick and safe procedure with minimal morbidity and
      mortality. This procedure requires very experienced surgeon. Patients profit
      especially from miniinvasivity and short convalescence. Especially benign tumours
      of smaller size (by 8 cm) are indicated, extensive and especially malignant
      tumours remain a domain of open approach. Previous operations in abdominal cavity
      do not have to be a contraindication for LA and operation is possible in patients
      with monster obesity.

PMID- 20052930
TI  - [Foreign bodies--uncommon causes of GIT injuries].
AB  - Injuries to various parts of the digestive tract caused by foreign bodies,
      frequently deliberately swallowed or inserted using various practics, are less
      common, however serious injuries. The symptomatology may be vague, credibility is
      often limited or anamnestic data may be intentionaly missing, which makes the
      diagnostic process tricky. Undefined, vague signs are related to specificities
      during the GIT perforation, so called hidden perforation. The recovery is
      commonly complicated, with a resulting handicap of stool incontinence or of
      colostomy. This is demonstrated on several subjects, treated in our surgical
      department.

PMID- 20052931
TI  - [Fast track concept in colorectal surgery in a regional hospital setting].
AB  - INTRODUCTION: Fast Track Concept is a draft of shorter and less stressful
      preoperative set up of patient, considerate operation technique and painless
      recovery with early start of enteral alimentation. AIM: This work presents Fast
      Track Concept and its possibilities in colorectal surgery. RESULTS: We have
      treated 108 patients with this method on our workplace from April 2005 till
      August 2007. All of them underwent mostly elective resection of colon. RESUME:
      Fast Track Concept in colorectal surgery is according to our opinion easy
      practicable even in conditions of smaller hospital and we assume, as well as
      literature says, that it is a benefit for the patient.

PMID- 20052932
TI  - [Fast track in intestinal surgery; current review].
AB  - INTRODUCTION: Results of the elective surgical procedures are affected not only
      by quality of the procedure, but also by perioperative care. Accelerated
      postoperative rehabilitation (fast track) reduces the frequency of postoperative
      complications, shortens the length of hospital stay and increases the patients'
      comfort. These modern procedures are subject to number of trials and they are
      even part of current European guidelines. AIM: The aim of this review is to
      evaluate scientific significance of the individual procedures in terms of fast
      track perioperative care and their comparison with traditional perioperative
      care. CONCLUSION: There is number of evidence that complex program of fast track
      postoperative rehabilitation improves postoperative healing. Its introduction
      into general practice could contribute to quality of perioperative care which
      differs greatly and often depends more on experiences than on scientific
      evidences.

PMID- 20052933
TI  - [Procedure on low extremities varicose veins using the VNUS-Closure
      radiofrequency ablation method].
AB  - From 01-06-2007 to 31-12-2008, the authors operated 334 patients with low
      extremities varicose veins, using the VNUS-Closure radiofrequency apparatus, in
      the surgical department of Pribram regional hospital (Oblastni nemocnice v
      Pribrami, a.s.). Their first experience is very positive, the method is very
      elegant, safe and miniinvasive. The mean duration of the procedure on a single
      lower extremity was 29 minutes, the mean duration of hospitalization was one day.
      Relapses were recorded in 3 patients in the operated area (0.9%), however, in all
      the subjects, the relaps affected a side venous branch, never the main branch.
      The relapses were managed with subsequent sclerotization. The method was patient-
      friendly, reliable and resulted in early return to work, was little painful and
      had favourable cosmetic outcomes. These were the factors, which made the patients
      choose the VNUS-Closure endoluminal radiofrequency method.

PMID- 20052934
TI  - [Our actions should be responsible and rational].

PMID- 20052935
TI  - [Primary brain tumor as a rare cause of acute subdural hematoma].
AB  - The aim of the study is to present a case report describing patient, admitted for
      subdural haematoma located on temporal lobe base and brain convexity with
      intracerebral haematoma located in the depth of temporal lobe. Both haematomas
      were evacuated from burr holes. Histological analysis of tissue obtained during
      intracerebral haematoma aspiration has proven tumorous tissue consistent with
      anaplastic astrocytoma. Contrast enhanced MRI has confirmed the diagnosis and
      patient underwent tumor surgery. The study brings additional data to differential
      diagnosis of subdural haematoma, especially of non traumatic origin. When
      compared with meningiomas and metastatic tumors primary brain glioma is an
      exceptional cause of subdural haematoma of non traumatic origin.

PMID- 20052936
TI  - [Comparative clinical study assessing C2 dens injuries treatment outcomes].
AB  - The aim of this restrospective study was to compare treatment outcomes of C2 dens
      fractures following their conservative or surgical management, using direct
      osteosynthesis with canalised screws and the Dens Access device. During 1999
      2006, 108 patients with type II and type III dens injuries, based on the Anderson
      D'Alonzo classification, were treated in the Brno Traumatology Hospital (Urazova
      nemocnice Brno). Patients with type I injuries were excluded from the study. The
      study included 32 patients, who presented for a chek-up. Out of the total, 15
      patients had undergone surgery, 17 had been managed conservatively. The mean age
      was 56 years (17-83 y.o.a.), 19 subjects were males and 13 subjects were females.
      The conservative treatment included the following methods: treatment with a
      Philadelphia collar (4 subjects) or a halo apparatus (13 subjects). Only
      patients, in whom at least a year elapsed since their injury, were included in
      the study. The control group showed inferior results on ROM (range of motion),
      VAS (Visual analogue scale) and x-ray examinations. Overall, in the conservative
      group, 3 subjects showed restricted cervical range of motion, compared to a
      single subject in the operated group. The mean VAS was 3.6 (0-7) in the
      conservative group, compared to the mean VAS of 2.9 (0-6) in the operated group.
      No fragment displacements or development of a pseudojoint was recorded in the
      operated subjects. In the conservative group, fragment displacement was observed
      in 2 subjects. In the both subjects, the bone healed. The Fisher's exact test and
      the Mann-Whitney U-test were used for statistical analysis of the data.

PMID- 20052937
TI  - [Spontaneous pneumothorax--management, therapy].
AB  - OBJECTIVE: Spontaneous pneumothorax (SPNO) is a surgical disease, which belongs
      to surgical emergencies. It is divided into a primary, secundary, katamenial and
      neonatal. A young and healthy men are affected by primary SPNO, usually on the
      right side of the thorax, recurrence is common. A secondary SPNO typically occurs
      in patients between the 5th and 7th decenium. These patients usually suffer from
      some lung disease. A major complications are more common in this type of
      pneumothorax. METHODS: At Department of surgery, University Hospital Brno, 73
      patients were treated for spontaneous pneumothorax from the January, 2006 till
      August, 2008. We divided patients in two groups. The first one with primary SPNO,
      and the second one with secondary SPNO. Hospital stay, age distribution, type of
      operation, duration of drainage, postoperative complication, histological
      findings and laterality were followed up retrospectively. RESULTS: In group of
      primary SPNO, 24 patients were operated without major complication. The most
      frequent cause was bullate emphysema, hospital stay was 8 days, duration of
      drainage 6 days. The second group with secondary SPNO, five patients were
      operated, hospital stay was 16.5 days, duration of drainage 10 days. Haemothorax
      as a postoperative complication occured in one case. In both groups we proved the
      bullate emphysema as the most frequent cause, as well as a right - sided
      involvement. CONCLUSION: Spontaneous pneumothorax is a surgical disease. It's
      treatment has to be provided by surgeon, if possible by a thoracic specialist.
      The first occurrence of spontaneous pneumothorax is treated by drainage, the
      recurrence by operation. The principal is to combine an atypical resection of
      affected lung with a mechanical pleurodesis. Postoperative complications are not
      frequent.

PMID- 20052938
TI  - [Fulminant acute pancreatitis].
AB  - INTRODUCTION: Fulminant acute (FAP) and subfulminant pancreatitis (SFAP)
      represent the latterly defined subgroup within the severe acute pancreatitis
      (SAP) with rapidly progressing organ failure (OF) and multi-organ failure MOF
      high level of lethality and poor effect of both conservative and surgical
      treatment. AIM AND METHODS: Analysis of indigenous set of patients diagnosed with
      SAP, particularly with FAP and SFAP, and comparison of data with the literature.
      Retrospectively prospective study of data collected over the period 2003 to 2007.
      RESULTS: Mild form of AP (MAP) 128 p., etiology %: biliary/alcohol/other -
      52/36/12; SAP 106 p., etiology %: biliary/alcohol/other - 51/41/9; ESAP 21 p.
      i.e. 20% of SAP, aetiology %: biliary/alcohol/other - 3/27/39. Age: MAP/SAP/ESAP 
      43.2/45.8/46.1. Lethality %: MAP/SAP/ESAP: 0/19/71.5% (i.e. 78.5% of all deaths
      of TAP. ESAP 21 p., FAP 6 p., SFAP 15 p. FAP/SFAP: M/F 3/3 or 11/4, age 44.5 (17
      81) or 46.8 (25-73). FAP etiology: 1x biliary, 1x alcohol, 4x?; SFAP: 6x biliary,
      5x alcohol, 4x?. FAP: 4x severe hypercholesterolemia or hypertriglyceridemia,
      SFAP dtto 3x. FAP lethality: 83%, SFAP: 67%. Mean survival rate: FAP 4.1 d., SAP
      9.2 d. FAP treatment: conservative 3 p., surgical 3 p., hemoelimination 2 p. SFAP
      treatment: conservative 9 p., surgical 6 p (reoperated 92% of all surgically
      treated, 7x on average), hemoelimination 8 p. DISCUSSION: Mortality prediction
      especially in FAP and SAP--progression and early occurrence of organ failure and
      its dynamics, existence of organ failure at the time of patient's admission and
      its rapid deterioration. Action of age, comorbidity and aetiology: insufficient
      data for meta-analysis; difference between ESAP and LAP has no statistic
      importance. Indigenous set of patients proves incidence, progression and
      lethality in FAP and SFAP, demonstrates higher incidence of hyperlididemia and
      hypercholesterolemia in FAP (60%) compared to SFAP with far more frequent biliary
      or alcohol aetiology. Among FAP, SAP and LSAP no age-dependent differences were
      proved. Absolute dominance of organ failure symptoms, suspicion to infected
      necrosis rather rarely expressed. Differences in prognosis in relation to applied
      treatment--either conservative or surgical (FAP surgery 50%, SFAP surgery 60%)
      were not observed. In section severe destructive findings in pancreas and its
      vicinity as well as extensive organ lesions were observed. CONCLUSION: Our own
      results are in concord with the results of other studies. It appears pretty
      useful to search for further ESAP predicting factors within meta-analytical
      studies. Intensive resuscitation care since the admission is a necessity, despite
      that, particularly in FAP, the results are unfavourable; surgical treatment has
      higher impact in SFAP than in AP, where often is ultimum refugium only.

PMID- 20052939
TI  - [The current view of surgical treatment of diverticular disease].
AB  - AIM: The aim of our prospective dynamic cohort trial is the evaluation of
      indication for surgery for diverticular disease and the evaluation of morbidity
      and mortality. MATERIAL AND METHOD: All patients operated for diverticular
      disease and its complications were involved in the study. The conservatively
      treated patients were not involved. 104 patients with diverticular disease and
      its complication were operated from August 2007 till July 2008.46 men and 58
      women at average age of 63.9 (31-85) years were in this group. 78 patients were
      electively operated in noninflammatory stage of diverticular disease. 3 patients
      of them had colovesical or enterocolical fistulas. An elective laparoscopic colon
      sigmoid resection was performed by 74 patients and a laparoscopic left
      hemicolectomy was performed by 4 patients. An end-to-end stapled colorectal
      suture was performed by all patients. An excision of fistula from urinary bladder
      and a segment resection of small bowel were performed in the case of fistula
      presence. In connection with previously repeated diverticulitis attacks or after
      previous surgeries, adhesiolysis was performed by 23 patients. 26 patients were
      operated for acute complication of diverticular disease. 24 patients of this
      group were operated for acute diverticulitis and 2 patients for diverticular
      bleeding. 23 colon sigmoideum resections, 2 left hemicolectomies, and once
      ileocecal resection were performed. The primary bowel suture was performed by 20
      patients and Hartmaruts operation was performed by 4 patients. RESULTS: The
      indication for surgery follows the classification according to Hansen and Stock.
      The abdominal postoperative complications (wound infection, anastomotic leak,
      prolongated bowel atonia, and others) occurred by elective operated group in 9%
      and by acute operated group in 26.9%. The overall abdominal postoperative
      complications occurred in all the involved patients in 13.4%. The extraabdominal
      postoperative complications (urinary infection or retention, cardiopulmonary
      complications, trombosis/embolia, postoperative qualitative conscious disorder,
      renal insufficiency, and others) occurred by elective group in 19.6% and by acute
      operated group in 50%. Overall extraabdominal postoperative complications
      occurred in all involved patients in 26.90%. The mortality was 0%. The conversion
      rate in elective group was 3.8% (3 pts.). An anastomosis leak occurred once (1%)
      by elective operated patient. An acute reoperation with resection according to
      Hartmann was performed. A small bowel loop perforation by coincidental
      adhesiolysis occurred once. A small bowel defect was identified and sutured by
      early laparoscopic reoperation. The conversion rate in acute group was 23.1% (6
      pts.). The colonoscopy was necessary on 3rd day by 1 patient after left
      hemicolectomy for splenic flexure bleeding. This examination revealed bleeding
      from diverticulum in hepatic flexure. An endoscopic treatment was performed. An
      abscess in small pelvis occurred by this patient (12th postoperative day) and
      open drainage was performed. There was no anastomosis leak in group with acutely
      operated patients. CONCLUSION: The usage of standard classification is suitable
      for operation's indication for diverticular disease and its complications. It
      helps to determine the type and operation's strategy. The acute complicated
      diveticulitis has high morbidity and mortality. The early indication of selected
      patients with diverticular disease for elective colon sigmoideum resection
      protects against possible complication in the case of next attack of
      diverticulitis. It concerns the patients with recidivated uncomplicated and
      complicated forms of disease as well. The primary conservative treatment with
      percutaneous CT navigated drainage allows a postponed elective surgery. The
      primary resection with suture is better than the two stage surgery. The primary
      laparoscopic resection is safe procedure in almost all the cases. The primary
      suture can be safely performed in all elective cases for uncomplicated
      diverticulitis, chronic fistulas, obstruction, for primarily conservatively
      treated stages Hinchey I and II and possibly for all the selected patients with
      Hinchey III and IV stages with MPI lower as 21.

PMID- 20052940
TI  - [Intestinal diverticulum localized in antimesenterial side of jejunum as a reason
      of perforation peritonitis--case report].
AB  - Authors present the case of patient with perforation of atypicaly localised
      diverticula of small intestine. The most important in clinical picture of patient
      was the sudden progress of sepsis and symptoms of organ failure. This status was
      progreding after the first operative revision of abdominal cavity when no
      explanation for peritonitis was found. During the second operation revision we
      found the perforated diverticula of the mesenterial side of distal jejunum. In
      the period after operation several complications such as wound healing failure
      and organs failure were occurred.

PMID- 20052941
TI  - [Treatment of hernia ventralis permagna].
AB  - The authors present case report about two patients with hernia ventralis
      permagna. Both patients were treated urgently for strangulation in hernial bag.
      The elective surgery was delayed for various reasons and, at the end, they were
      operated acutely using the polypropylene net. The authors prefer the more active
      approach to the indication of elective surgery.

PMID- 20052942
TI  - [Bedside ultrasonographic examination of a critically ill surgical patient].
AB  - INTRODUCTION: Bedside ultrasonography is a modern and progressive examinating
      method. During the past two decades, performing of bedside ultrasonography has
      repeteadly shown its clinical and economical advantages. Bedside ultrasonography
      appears to be cost-effective method which provides minimall patient and staff
      stress. AIM AND METHOD: 132 critically ill patients were involved, regardless of
      basic diagnosis and surgical procedure they undervent. In these patients both
      bedside USG and CT were performed in order to prove a fluid collections in one of
      the following anatomical locations pleural cavity, peritoneal cavity and
      abdominal wall. The prospective study assessed and compared sensitivity of
      bedside USG to CT. Results of the study should by further applied in hardly
      transportable critically ill, for that CT could be hazardous. RESULTS AND
      CONCLUSION: Bedside USG had comparable sensitivity to CT in fluidothrorax and
      abdominal wall colections detection, in some cases even more. For intraabdominal
      fluid USG represent less accurate method to CT, benefit of CT should be then
      discussed in each patient individually considering general health condition and
      basic diagnosis.

PMID- 20052943
TI  - [Peroperative diagnostics of acute bowel ischemia using ultraviolet light and
      fluorescein dye].
AB  - Acute bowel ischemia continues to have a high mortality rate. The main factor
      related to this poor outcome is considered to be the delay in diagnosis. The
      ability to detect ischemia early and to assess the extent of bowel involvement,
      are the most important aspects of successful treatment. The combination of
      ultraviolet (UV) light and fluorescein dye would be considered a simple, reliable
      and technically easy procedure for diagnosis of intestinal ischemia. The method
      can be used both for laparotomy when the source of UV light is a Wood's lamp as
      well for laparoscopy when the optical filters are placed to the light source of
      laparoscopic set to produce UV light. Present clinical experience shows that the
      method is precise, objective and accessible and that it gives a greater amount of
      independence to the surgeon allowing him to make the diagnosis of intestinal
      ischemia without having to rely on the assistance of other specialists.

PMID- 20052944
TI  - [Acetabular erosion after hip hemiarthroplasty. Clinical and biomechanical
      study].
AB  - Acetabular erosion is the most serious late complication of the hemiarthroplasty
      of the hip. We analyzed the factors influencing acetabular erosion after
      hemiarthroplasty for intracapsular femoral neck factures. Twelve patients of
      average age 71 years initially treated by one type of hemiarthroplasty in which
      conversion to total hip arthroplasty was performed due to pain and acetabular
      erosion. Evaluation was made of the interval between hemiarthroplasty and
      revision, indication for conversion and position of the head with regard to the
      apex of the greater trochanter. In case of a marked erosion of the acetabulum the
      evaluation included also the direction of the head migration. The basic group was
      further divided into two groups. The first group included 7 patients with an
      early revision, i.e. on average 22 months. The second group comprised 5 patients
      with a late revision at the average interval between the primary surgery and
      revision of 68 months. High position of the prosthetic head was found out in all
      patients of the first group while neutral or low position was recorded in all
      patients of the second group. In 7 cases with marked acetabular erosion we
      reconstructed the direction of the prosthesis migration. We recorded three
      directions of migration of the prosthetic head--proximomedial, purely proximal
      and proximolateral. The direction of migration depended on the position of the
      head, CE angle and position of the prosthetic stem in the medullary canal. The
      resection level of the femoral neck and resulting from it the position of the
      prosthetic head is a significant factor influencing the progress of acetabular
      erosion.

PMID- 20052945
TI  - [Minimally invasive plate osteosynthesis (MIPO) in the humeral diaphysis
      fractures].
AB  - INTRODUCTION: Most of the humeral shaft fractures can be successfully treated
      conservatively. Due to increasing number of multiple and high-energy injuries,
      necessity of patient's compliance and restriction of his selfcare is conservative
      treatment in background. Humeral shaft fractures indicated to operation treatment
      are mostly solved by closed reposition and internal fixation with intramedullar
      nail (CRIF) or open reposition and internal fixation (ORIF). AIM: The aim is to
      prove that miniinvasive plate osteosynthesis (MIPO) of the humeral shaft
      fractures combines advantages of the both currently used methods. In other words,
      to use a plate osteosynthesis with minimal invasiveness and to exclude unexpected
      complications of radical operation approach by open reposition and problems
      related to nailing. MATERIAL AND METHOD: From March 2007 to August 2008 we
      operated on 20 patients with humeral shaft fractures using MIPO technique.
      Fractures were classified according to AO-classification: A - 9x, B - 5x, C - 6x.
      There were monotraumas and multiple injuries, as well. RESULTS: The results were
      evaluated by Constant-Murley test and Liverpool elbow scoring system. The mean
      value was 92/9.1 points. In 75% of patients we have reached good and excellent
      results. Complications were observed in 5 patients (20%). All patients have been
      healed. CONCLUSION: In spite of the limited number of patients in case serie our
      results are in accordance with current published data. Minimally invasive plate
      osteosynthesis is in our opinion safe and effective operation method for humeral
      shaft fractures treatment.

PMID- 20052946
TI  - Radiologic case study. Lymphoma of the distal femur.

PMID- 20052947
TI  - Full disclosure.

PMID- 20052948
TI  - Lose a leg.

PMID- 20052949
TI  - Cap and no trade.

PMID- 20052950
TI  - Modified margin convergence technique using suture anchors for footprint
      reconstruction of rotator cuff tears.

PMID- 20052951
TI  - New and upcoming biologic agents for rheumatoid arthritis.

PMID- 20052952
TI  - ACL prevention programs: fact or fiction?

PMID- 20052953
TI  - Quadriceps tendon injuries.

PMID- 20052956
TI  - The ethical dilemma of life-prolonging medical devices.

PMID- 20052957
TI  - Helpful tips for performing musculoskeletal injections.
AB  - Injections are valuable procedures for managing musculoskeletal conditions
      commonly encountered by family physicians. Corticosteroid injections into
      articular, periarticular, or soft tissue structures relieve pain, reduce
      inflammation, and improve mobility. Injections can provide diagnostic information
      and are commonly used for postoperative pain control. Local anesthetics may be
      injected with corticosteroids to provide additional, rapid pain relief. Steroid
      injection is the preferred and definitive treatment for de Quervain tenosynovitis
      and trochanteric bursitis. Steroid injections can also be helpful in controlling
      pain during physical rehabilitation from rotator cuff syndrome and lateral
      epicondylitis. Intra-articular steroid injection provides pain relief in
      rheumatoid arthritis and osteoarthritis. There is little systematic evidence to
      guide medication selection for therapeutic injections. The medication used and
      the frequency of injection should be guided by the goal of the injection (i.e.,
      diagnostic or therapeutic), the underlying musculoskeletal diagnosis, and
      clinical experience. Complications from steroid injections are rare, but
      physicians should understand the potential risks and counsel patients
      appropriately. Patients with diabetes who receive periarticular or soft tissue
      steroid injections should closely monitor their blood glucose for two weeks
      following injection.

PMID- 20052958
TI  - Promoting physical activity in older adults.

PMID- 20052960
TI  - Effectiveness of acupuncture for migraine prophylaxis.

PMID- 20052959
TI  - Statins for non-dialysis chronic kidney disease.

PMID- 20052961
TI  - Cervical radiculopathy: nonoperative management of neck pain and radicular
      symptoms.
AB  - Cervical radiculopathy is a disease process marked by nerve compression from
      herniated disk material or arthritic bone spurs. This impingement typically
      produces neck and radiating arm pain or numbness, sensory deficits, or motor
      dysfunction in the neck and upper extremities. Magnetic resonance imaging or
      computed tomographic myelography can confirm neurologic compression. The overall
      prognosis of persons with cervical radiculopathy is favorable. Most patients
      improve over time with a focused, nonoperative treatment course. There is little
      high-quality evidence on the best nonoperative therapy for cervical
      radiculopathy. Cervical collars may be used for a short period of immobilization,
      and traction may temporarily decompress nerve impingement. Medications may help
      alleviate pain and neuropathic symptoms. Physical therapy and manipulation may
      improve neck discomfort, and selective nerve blocks target nerve root pain.
      Although the effectiveness of individual treatments is controversial, a
      multimodal approach may benefit patients with cervical radiculopathy and
      associated neck pain.

PMID- 20052962
TI  - LASIK: a primer for family physicians.
AB  - Surgical correction of vision is becoming increasingly popular. Laser-assisted in
      situ keratomileusis (LASIK) is the most popular method of corneal refractive
      surgery. LASIK is usually limited to adults who have stable refraction.
      Contraindications include the use of certain medications, conditions that impair
      healing, abnormal corneal anatomy, and inadequate tearing. Patients who cannot
      tolerate persistent eye dryness or who engage in activities with a risk of eye
      trauma should avoid LASIK. Possible complications include diffuse lamellar
      keratitis, epithelial ingrowth, and fap complications. Almost all patients
      achieve uncorrected visual acuity of at least 20/40, but higher degrees of
      preoperative myopia may require a second operation. Long-term data on safety and
      stability are just becoming available. LASIK appears to be safe and effective,
      with only a small tendency for increased myopia in the first few years after
      surgery.

PMID- 20052963
TI  - Physical activity guidelines for older adults.
AB  - Few older adults in the United States achieve the minimum recommended amount of
      physical activity. Lack of physical activity contributes to many chronic diseases
      that occur in older adults, including heart disease, stroke, diabetes mellitus,
      lung disease, Alzheimer disease, hypertension, and cancer. Lack of physical
      activity, combined with poor dietary habits, has also contributed to increased
      obesity in older persons. Regular exercise and increased aerobic fitness are
      associated with a decrease in all-cause mortality and morbidity, and are proven
      to reduce disease and disability, and improve quality of life in older persons.
      In 2008, The U.S. Department of Health and Human Services released guidelines to
      provide information and guidance on the amount of physical activity recommended
      to maintain health and fitness. For substantial health benefits, the guidelines
      recommend that most older adults participate in at least 150 minutes of moderate
      intensity aerobic activity, 75 minutes of vigorous-intensity aerobic activity, or
      an equivalent combination of each per week. Older adults should also engage in
      strengthening activities that involve all major muscle groups at least two days a
      week. Those at risk of falling should add exercises that help maintain or improve
      balance. Generally healthy adults without chronic health conditions do not need
      to consult with a physician before starting an exercise regimen.

PMID- 20052964
TI  - Retinal changes and visual impairment.

PMID- 20052966
TI  - Correlation of clinical and immunological data in a metastatic melanoma patient
      with heterogeneous tumor responses to ipilimumab therapy.
AB  - Melanoma patients treated with anti-CTLA-4 have shown a range of anti-tumor
      responses. In this report, we describe the response of a single patient to anti
      CTLA-4, with individual lesions disappearing, others stabilizing, and others
      progressing. These responses can be viewed as a clear manifestation of cancer
      immunoediting and its three phases of elimination, equilibrium and escape, with
      each tumor in this patient being at a discrete stage in the process. The
      patient's course and associated immunological monitoring and other laboratory
      data are presented in an immunogram, a way to visualize temporal associations
      between the multiple clinical and laboratory parameters.

PMID- 20052967
TI  - Crystal structure of the cofactor-independent monooxygenase SnoaB from
      Streptomyces nogalater: implications for the reaction mechanism.
AB  - SnoaB is a cofactor-independent monooxygenase that catalyzes the conversion of 12
      deoxynogalonic acid to nogalonic acid in the biosynthesis of the aromatic
      polyketide nogalamycin in Streptomyces nogalater. In vitro (18)O(2) experiments
      establish that the oxygen atom incorporated into the substrate is derived from
      molecular oxygen. The crystal structure of the enzyme was determined in two
      different space groups to 1.7 and 1.9 A resolution, respectively. The enzyme
      displays the ferredoxin fold, with the characteristic beta-strand exchange at the
      dimer interface. The crystal structures reveal a putative catalytic triad
      involving two asparagine residues, Asn18 and Asn63, and a water molecule, which
      may play important roles in the enzymatic reaction. Site-directed mutagenesis
      experiments, replacing the two asparagines individually by alanine, led to a 100
      fold drop in enzymatic activity. Replacement of an invariant tryptophan residue
      in the active site of the enzyme by phenylalanine also resulted in an enzyme
      variant with about 1% residual activity. Taken together, our findings are most
      consistent with a carbanion mechanism where the deprotonated substrate reacts
      with molecular oxygen via one electron transfer and formation of a caged radical.

PMID- 20052968
TI  - Hydrocarbon gas standards at the pmol/mol level to support ambient atmospheric
      measurements.
AB  - Studies of climate change increasingly recognize the diverse influences exerted
      by hydrocarbons in the atmosphere, including roles in particulates and ozone
      formation. Measurements of key non-methane hydrocarbons (NMHCs) suggest
      atmospheric concentrations ranging from low pmol/mol to nmol/mol, depending on
      location and compound. To accurately establish concentration trends and to relate
      measurement records from many laboratories and researchers, it is essential to
      have good calibration standards. Several of the world's National Metrology
      Institutes (NMIs) are developing primary and secondary reference gas standards at
      the nmol/mol level. While the U.S. NMI, the National Institute of Standards and
      Technology (NIST), has developed pmol/mol standards for halocarbons and some
      volatile organics, the feasibility of preparing well-characterized, stable
      standards for NMHCs at the pmol/mol level is not yet established. NIST recently
      developed a suite of primary standards by gravimetric dilution that contains 18
      NMHCs covering the concentration range of 60 pmol/mol to 230 pmol/mol. Taking
      into account the small but chemically significant contribution of NMHCs in the
      high-purity diluent nitrogen used in their preparation, the relative
      concentrations and short-term stability (2 to 3 months) of these NMHCs in the
      primary standards have been confirmed by chromatographic analysis. The
      gravimetric values assigned from the methods used to prepare the materials and
      the analytical concentrations determined from chromatographic analysis generally
      agree to within +/-2 pmol/mol. However, anomalous results for several of the
      compounds reflect the difficulties inherent in avoiding contamination and making
      accurate measurements at these very low levels.

PMID- 20052969
TI  - Small-molecule diselenides catalyze oxidative protein folding in vivo.
AB  - Prokaryotic cells normally rely on periplasmic oxidoreductases to promote
      oxidative protein folding. Here we show that simple diselenides can also
      facilitate the conversion of dithiols to disulfides in vivo, functionally
      replacing one such oxidoreductase, DsbA, in the oxidative folding of diverse
      proteins. Structurally analogous disulfides provide no detectable effect when
      used at concentrations that gave optimal activity with diselenides, and even at
      100- to 1000-fold higher levels they show only partial activity. The low
      concentrations of diselenides needed to fully negate typical DsbA knockout
      phenotypes suggest catalysis in vivo, a property that sets these additives apart
      from other small molecules used in chemical biology. Supplementing growth media
      with cell-permeable organocatalysts provides a potentially general and
      operationally simple means of fine-tuning the cellular redox environment.

PMID- 20052970
TI  - Cysteine oxidation enhanced by iron in tristetraprolin, a zinc finger peptide.
AB  - Tristetraprolin (TTP or NUP475) is a non-classical zinc finger protein that is
      involved in inflammatory response. TTP regulates the production of cytokines by
      binding to specific mRNA sequences. TTP contains two Cys(3)His metal binding
      domains that can coordinate zinc, cobalt, ferric and ferrous iron. When zinc,
      cobalt, ferric or ferrous iron are bound, TTP peptides can bind to their cognate
      RNA. During inflammation there are increased levels of reactive oxygen species
      and iron. It has been proposed that reactive oxygen species may play a role in
      regulating zinc finger protein function by oxidizing cysteine thiolates that bind
      zinc and inactivating the protein. To elucidate the effect of the reactive oxygen
      species H(2)O(2) on the integrity of TTP and its ability to bind to target RNA, a
      simple and rapid assay using cobalt as a spectroscopic probe for zinc was
      developed. The oxidative susceptibility of peptides consisting of the zinc
      binding domains of a single zinc finger domain of TTP, TTP-D1 and the tandem zinc
      finger domains of TTP, TTP-2D was measured. Fe(II)-TTP-D1 and Fe(II)-TTP-2D were
      more rapidly oxidized by H(2)O(2) than their Zn(II) bound counterparts. Electron
      paramagnetic resonance (EPR) spin trapping using 2-ethoxycarbonyl-2-methyl-3,4
      dihydro-2H-pyrrole-1-oxide (EMPO) demonstrated that oxidation of ferrous iron
      substituted TTP-D1 and TTP-2D resulted in the formation of hydroxyl radicals via
      Fenton chemistry. The oxidized peptides exhibited a diminished affinity for
      target RNA compared to their unoxidized counterparts suggesting that oxidation of
      TTP inactivates the protein.

PMID- 20052971
TI  - Hydroxylated sclerosporin derivatives from the marine-derived fungus Cadophora
      malorum.
AB  - The marine-derived fungus Cadophora malorum was isolated from the green alga
      Enteromorpha sp. Growth on a biomalt medium supplemented with sea salt yielded an
      extract, from which we have isolated sclerosporin and four new hydroxylated
      sclerosporin derivatives, namely, 15-hydroxysclerosporin (2), 12
      hydroxysclerosporin (3), 11-hydroxysclerosporin (4), and 8-hydroxysclerosporin
      (5). The compounds were evaluated in various biological activity assays. Compound
      5 showed a weak fat-accumulation inhibitory activity against 3T3-L1 murine
      adipocytes.

PMID- 20052972
TI  - Urinary excretion of phenolic acids in rats fed cranberry.
AB  - Dietary flavonoids can be converted into phenolic acids by colonic microflora.
      Phenolic acids can then be absorbed into the circulation and may contribute to
      the health-promoting effects of the parent compounds. Phenolic acids can be
      further metabolized in other tissues via methylation and conjugation with
      glucuronide or sulfate. The objectives of this study were to identify and
      quantify the urinary excretion of 19 phenolic acids and their conjugates in rats
      fed three levels of a concentrated cranberry powder (3.3, 6.6, and 33 mg/kg of
      diet). The basic diet used was AIN93G diet containing very low amounts of any
      polyphenolic compounds. Of the phenolic acids studied, the amounts excreted
      varied by 4 orders of magnitude, with hippuric acid being excreted in the highest
      quantities. Amounts of 4-hydroxyphenylacetic acid (4HPAA), 3-hydroxyphenylacetic
      acid (3HPAA), 3-hydroxyphenylpropionic acid (3HPPA), and 4-hydroxycinnamic acid
      (4HCA) excreted were in the range of 18-33 microg/mg creatinine in animals fed
      the highest level of cranberry powder, whereas phenylacetic acid (PAA), gallic
      acid (GA), 3,4-dihydroxyphenylacetic acid (34HPAA), 3,4-dihydroxybenzoic acid
      (34HBA), 3,4-dihydroxycinnamic acid (34HCA), and 4-hydroxy-3-methoxycinnamic acid
      (FA) were excreted in the urine in concentrations of 0.1-2 microg/mg creatinine.
      As the amount of cranberry in the diet was increased, the amount of 4HPAA
      excreted decreased but the percentage of conjugated 4HPAA excreted increased
      (from 57 to 91%). For other phenolic acids analyzed, the percentage excreted in
      the conjugated form was approximately constant across levels of cranberry in the
      diet and ranged from 65 to 100% for the individual phenolic acids. Studies of
      bioactivity and health effects need to consider more than just the compound(s) in
      the food, because they can be metabolized to other lower molecular weight
      compounds, which in turn may also be methylated or conjugated in some form that
      may affect the perceived health effects.

PMID- 20052973
TI  - Extraction, fractionation and characterization of bitter melon seed proteins.
AB  - Protein fractions (water-soluble/albumin, salt-soluble/globulin, alkali
      soluble/glutelin, and alcohol-soluble/prolamin) were extracted from defatted ripe
      bitter melon seed (Momordica charantia) using water, 1 M sodium chloride
      solution, alkali/pH 11.0, and 70% ethanol, sequentially. The main protein
      fraction was albumin (49.3%), followed by globulin (29.3%) and glutelin (3.1%).
      No prolamin was detected, and 18.3% of the protein was nonextractable. The
      surface hydrophobicities of albumin, globulin, and glutelin were 757, 1,034, and
      292, respectively. The molecular sizes of all the fractions were mostly about 45
      and 55 kDa. The denaturation temperatures of albumin, globulin, and glutelin were
      111.9, 117.3, and 133.6 degrees C, respectively. The levels of all essential
      amino acids in the bitter melon protein fractions met the minimum requirements
      for preschool children (FAO/WHO/UNU) with the exception of Thr. Bitter melon
      protein fractions with unique protein profiles and higher denaturation
      temperatures could impart novel characteristics when used as food ingredients.

PMID- 20052974
TI  - Enantioselective total synthesis of the natural gamma-tocopherol metabolite (S)
      gamma-CEHC [(S)-LLU-alpha].
AB  - The asymmetric synthesis of the natural gamma-tocopherol metabolite (S)-gamma
      CEHC (1) is described in 10 steps and 18.4% overall yield starting from 2,3
      dimethylhydroquinone. The key step is a stereoselective TiCl(4)-mediated
      homochiral sulfoxide-directed allylation of ketal (SS)-3 to efficiently generate
      the challenging C-2 stereogenic carbon of chroman (SS,S)-2 with the correct
      absolute configuration.

PMID- 20052975
TI  - A two-photon fluorescent probe for thiols in live cells and tissues.
AB  - We report a two-photon fluorescent probe (ASS) that can be excited by 780 nm
      femtosecond pulses and detect thiols in live cells and living tissues at a 90-180
      microm depth without interference from other biologically relevant species by two
      photon microscopy.

PMID- 20052976
TI  - The structural basis of Cryptosporidium -specific IMP dehydrogenase inhibitor
      selectivity.
AB  - Cryptosporidium parvum is a potential biowarfare agent, an important AIDS
      pathogen, and a major cause of diarrhea and malnutrition. No vaccines or
      effective drug treatment exist to combat Cryptosporidium infection. This parasite
      relies on inosine 5'-monophosphate dehydrogenase (IMPDH) to obtain guanine
      nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here,
      we report the first crystal structures of CpIMPDH. These structures reveal the
      structural basis of inhibitor selectivity and suggest a strategy for further
      optimization. Using this information, we have synthesized low-nanomolar
      inhibitors that display 10(3) selectivity for the parasite enzyme over human
      IMPDH2.

PMID- 20052977
TI  - Visualizing ascorbate-triggered release of labile copper within living cells
      using a ratiometric fluorescent sensor.
AB  - We present the synthesis, properties, and biological applications of Ratio
      Coppersensor-1 (RCS1), a new water-soluble fluorescent sensor for ratiometric
      imaging of copper in living cells. RCS1 combines an asymmetric BODIPY reporter
      and thioether-based ligand receptor to provide high selectivity and sensitivity
      for Cu(+) over other biologically relevant metal ions, including Cu(2+) and
      Zn(2+), a ca. 20-fold fluorescence ratio change upon Cu(+) binding, and visible
      excitation and emission profiles compatible with standard fluorescence microscopy
      filter sets. Live-cell confocal microscopy experiments show that RCS1 is membrane
      permeable and can sense changes in the levels of labile Cu(+) pools within living
      cells by ratiometric imaging, including expansion of endogenous stores of
      exchangeable intracellular Cu(+) triggered by ascorbate stimulation in kidney and
      brain cells.

PMID- 20052978
TI  - Enantioselective synthesis of allylic esters via asymmetric allylic substitution
      with metal carboxylates using planar-chiral cyclopentadienyl ruthenium catalysts.
AB  - An asymmetric allylic substitution with sodium carboxylate using a planar-chiral
      cyclopentadienyl ruthenium complex has been developed. Optically active allylic
      esters were prepared in good yields with high regio- and enantioselectivities.

PMID- 20052979
TI  - Recognition of patterned molecular ink with phage displayed peptides.
AB  - The development of a reliable method for patterning and recognizing molecular
      inks could enable exciting avenues in fundamental research and novel
      applications. Phage display is a powerful method for identifying peptides that
      possess enhanced selectivity and binding affinity toward a variety of targets.
      Here, we demonstrate for the first time the immobilization and recognition of a
      small molecular ink with screened phage displayed peptides. Our approach is based
      on a unique mix of comprehensive phage displayed peptide screening processes,
      along with novel micropatterning techniques. These results, combined with the
      large variety of available inks and surface chemistries, could open up
      opportunities in cell biology, nanomaterials self-assembly, selective sensors,
      and even energy storage applications.

PMID- 20052981
TI  - Large all-hydrocarbon spoked wheels of high symmetry: modular synthesis,
      photophysical properties, and surface assembly.
AB  - In a convergent modular synthesis, a very efficient pathway to shape-persistent
      molecular spoked wheels has been developed and applied according to the covalent
      template concept. The structurally defined two-dimensional (2D) oligo(phenylene
      ethynylene-butadiynylene)s (OPEBs) presented here are about 8 nm sized
      hydrocarbons of high symmetry. 48 alkyl chains attached to the molecular plane
      (hexyl and hexadecyl, respectively) guarantee a high solubility of the compounds.
      The structure and uniformity of these defined, stable, D(6h) symmetrical
      compounds is verified by MALDI-MS, GPC analysis, and high-temperature (HT) (1)H
      and (13)C NMR. Detailed photophysical measurements of nonaggregated molecules in
      solution (as confirmed by dynamic light scattering (DLS)) focus on the
      identification of chromophores by comparison with suitable model compounds.
      Moreover, time-resolved measurements including fluorescence lifetime and
      depolarization support the chromophore assignment and reveal the occurrence of
      intramolecular energy transfer. Scanning tunneling microscope (STM)
      characterization at the solid/liquid interface demonstrates the efficient self
      assembly of the OPEBs into hexagonal 2D crystalline layers with a periodicity
      determined by both the size of the OPEB backbone and the length of peripheral
      side chains. Atomic force microscope (AFM) studies show a very different assembly
      behavior of the two spoked wheel molecules, on both graphite and mica. While the
      hexyl-substituted wheel can form stacked superstructures, hexadecyl groups
      prevent any ordering in the film aside from the monolayer directly in contact
      with the surface.

PMID- 20052980
TI  - Unique catalytic mechanism of phosphatidylinositol-specific phospholipase C from
      Streptomyces antibioticus.
AB  - Calcium-dependent phosphatidylinositol-specific phospholipase C from Streptomyces
      antibioticus (saPLC1) catalyzes hydrolysis of phosphatidylinositol (PI) into
      inositol 1-phosphate by a unique mechanism involving formation of inositol 1,6
      cyclic phosphate (1,6-IcP) as an intermediate. This work examines the rates and
      products of cleavage of phosphorothioate and phosphorodithioate analogues of PI
      in which sulfur was introduced into the phosphate moiety at a nonbridging
      position (pro-R or pro-S), a bridging position, or both. The replacement of the
      pro-S oxygen in the phosphoryl moiety of PI by sulfur results in a 3 x 10(7)-fold
      decrease of the catalytic rate constant, whereas alteration of the pro-R oxygen
      results in only a modest rate reduction. The addition of the second sulfur atom
      into the bridging position of the S(p) isomer of the phosphorothioate analogue
      causes a dramatic (2 x 10(5)-fold) increase of the rate of cleavage but has a
      negligible effect on the R(p) isomer. These differences are consistent with a
      change in the mechanism for the S(p) isomer of the phosphorodithioate analogue
      into a more dissociative type, where the leaving group carries a large amount of
      negative charge. In addition, hydrolysis of the diastereomers of the
      phosphorothioate analogues of 1,6-IcP, inositol cis-1,6-IcPs and inositol trans
      1,6-IcPs, affords two distinct products, inositol 1-phosphorothioate and inositol
      6-phosphorothioate, respectively. Formation of inositol 6-phosphorothioate is
      explained by the binding of trans-1,6-IcPs in the active site in a rotated
      orientation that interchanges the oxygen atoms at the 1- and 6-positions, thereby
      allowing the hydroxyl group at the 1-position to act as a leaving group. The
      reorientation of the intermediate is driven by formation of favorable
      interactions of the enzyme active site with the nonbridging oxygen in the trans
      intermediate.

PMID- 20052982
TI  - Amine- and dimeric amino-borane complexes of the {Rh(P(i)Pr3)2}+ fragment and
      their relevance to the transition-metal-mediated dehydrocoupling of amine
      boranes.
AB  - Complexes formed between {Rh(P(i)Pr(3))(2)}(+) or {Rh(H)(2)(P(i)Pr(3))(2)}(+)
      fragments and the amine- and dimeric amino-borane sigma ligands H(3)B.NMe(3) and
      [H(2)BNMe(2)](2) have been prepared and their solution and solid-state structures
      determined: [Rh(P(i)Pr(3))(2)(eta(2)-H(3)B.NMe(3))][BAr(F)(4)] (1),
      [Rh(P(i)Pr(3))(2){eta(2)-(H(2)BNMe(2))(2)}][BAr(F)(4)] (2),
      [Rh(H)(2)(P(i)Pr(3))(2)(eta(2)-H(3)B.NMe(3))][BAr(F)(4)] (3), and
      [Rh(H)(2)(P(i)Pr(3))(2){eta(2)-(H(2)BNMe(2))(2)}][BAr(F)(4)] (4) [Ar(F) =
      C(6)H(3)(CF(3))(2)]. The last compound was only observed in the solid state, as
      in solution it dissociates to give [Rh(H)(2)(P(i)Pr(3))(2)][BAr(F)(4)] and
      [H(2)BNMe(2)](2) due to steric pressure between the ligand and the metal
      fragment. The structures and reactivities of these new complexes are compared
      with the previously reported tri-isobutyl congeners. On the basis of (11)B and
      (1)H NMR spectroscopy in solution and the Rh...B distances measured in the solid
      state, the P(i)Pr(3) complexes show tighter interactions with the sigma ligands
      compared to the P(i)Bu(3) complexes for the Rh(I) species and a greater stability
      toward H(2) loss for the Rh(III) salts. For the Rh(I) species (1 and 2), this is
      suggested to be due to electronic factors associated with the bending of the
      ML(2) fragment. For the Rh(III) complexes (3 and 4), the underlying reasons for
      increased stability toward H(2) loss are not as clear, but steric factors are
      suggested to influence the relative stability toward a loss of dihydrogen,
      although other factors, such as supporting agostic interactions, might also play
      a part. These tighter interactions and a slower H(2) loss are reflected in a
      catalyst that turns over more slowly in the dehydrocoupling of H(3)B.NHMe(2) to
      give the dimeric amino-borane [H(2)BNMe(2)](2), when compared with the P(i)Bu(3)
      ligated catalyst (ToF 4 h(-1), c.f., 15 h(-1), respectively). The addition of
      excess MeCN to 1, 2, or 3 results in the displacement of the sigma-ligand and the
      formation of the adduct species trans-[Rh(P(i)Pr(3))(2)(NCMe)(2)][BAr(F)(4)]
      (with 1 and 2) and the previously reported
      [Rh(H)(2)(P(i)Pr(3))(2)(NCMe)(2)][BAr(F)(4)] (with 3).

PMID- 20052983
TI  - Cross-linked microcapsules formed from self-deactivating reactive
      polyelectrolytes.
AB  - Poly(methyl vinyl ether-alt-maleic anhydride) (PMM(0)) was partially hydrolyzed
      in a 9/1 acetonitrile-d(3)/D(2)O mixture and then diluted with an aqueous buffer
      and coated onto poly-L-lysine (PLL)-coated calcium alginate capsules. The
      resulting 50% hydrolyzed polymer (PMM(50)) is bound to the surface-immobilized
      PLL through both electrostatic and covalent interactions, resulting in a shell
      cross-linked hydrogel capsule that is resistant to chemical challenges. Further
      hydrolysis of PMM(50) in aqueous buffer was monitored by potentiometry and was
      found to proceed with a half-life time of about 2.5 min at 20 degrees C such that
      residual anhydride groups not consumed by cross-linking with PLL would be
      deactivated by hydrolysis within several minutes of shell formation, removing
      potential sites for undesired protein binding. Initial protein-binding tests
      involving incubation of the capsules in bovine serum albumin solutions for 24 h
      showed no indication of protein binding. The effects of coating temperature, PLL
      concentration and molecular weight, PMM(50) molecular weight, and multiple PLL
      PMM(50) coatings on shell morphology and behavior were studied using confocal
      fluorescence microscopy as well as chemical challenges involving sodium citrate
      and sodium hydroxide. The resilience of the cross-linked shell improved with
      increasing concentrations of PLL and decreasing molecular weight of PMM(50), both
      of which resulted in more polyelectrolyte being bound to the capsule. The
      permeability of these covalently cross-linked capsules was studied using
      fluorescently labeled dextrans and was found to be comparable to standard calcium
      alginate-PLL-alginate (APA) capsules.

PMID- 20052984
TI  - Novel anthracene materials for applications in lithography and reversible
      photoswitching by light and air.
AB  - Herein we demonstrate how the photoreaction between anthracenes and singlet
      oxygen ((1)O(2)) is employed for applications either as photoswitch or as
      photoresist. Thin films of the diaryl-alkyl anthracene 1 and the analogous
      oligomeric species 2 were irradiated under photomasks to generate pattern
      structures composed of 1/1-O(2) and 2/2-O(2). Kelvin probe force microscopy
      (KPFM) provided a powerful and nondestructive method to image the pattern
      information. The following studies based on AFM, KPFM and contact angle
      measurements unfold that the two species 1 and 2 underwent different progressions
      after the imaging step. Degrading is observed for the monomeric compound 1 and
      the pattern eventually becomes recognizable in topography. In the oxidized state
      (1-O(2)) the monomeric species remains physically stable. In consequence, the
      unreacted portion is removable and the remaining oxygenated form 1-O(2) is
      sufficiently stable to protect an underlying substrate (e.g., silver) from
      etching. Thus, the system 1/1-O(2) operates as photoresist. On the other hand,
      both states of the oligomer 2 remain stable. The film is stable up to
      temperatures >120 degrees C required to erase the pattern within acceptable time
      by cycloreversion. Anthracene 2 therefore acts as erasable and rewritable
      photochromic switch. The different behavior between 1 and 2 is explained by phase
      transitions which cause crystallization and finally ablation. Such transitions
      affect only the monomeric system 1/1-O(2) and not the oligomeric system 2/2-O(2).
      In conclusion, we designed two very similar materials based on diarylanthracenes,
      which can act either as a photoresist or as a rewritable photochromic switch.

PMID- 20052985
TI  - Polymeric microcapsules assembled from a cationic/zwitterionic pair of responsive
      block copolymer micelles.
AB  - Using a layer-by-layer (LbL) approach, this work presents the preparation of
      hollow microcapsules with a membrane constructed entirely from a
      cationic/zwitterionic pair of pH-responsive block copolymer micelles. Our
      previous work with such systems highlighted that, in order to retain the
      responsive nature of the individual micelles contained within the multilayer
      membranes, it is important to optimize the conditions required for the selective
      dissolution of the sacrificial particulate templates. Consequently, here, calcium
      carbonate particles have been employed as colloidal templates as they can be
      easily dissolved in aqueous environments with the addition of chelating agents
      such as ethylenediaminetetraacetic acid (EDTA). Furthermore, the dissolution can
      be carried out in solutions buffered to a desirable pH so not to adversely affect
      the pH sensitive micelles forming the capsule membranes. First, we have deposited
      alternating layers of anionic poly[2-(dimethylamino)ethyl methacrylate-block
      poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) and cationic poly(2
      (diethylamino)ethyl)methacrylate-block-poly(methacrylic acid) (PDEA-PMAA)
      copolymer micelles onto calcium carbonate colloidal templates. After deposition
      of five micelle bilayers, addition of dilute EDTA solution resulted in
      dissolution of the calcium carbonate and formation of hollow polymer capsules.
      The capsules were imaged using atomic force microscopy (AFM) and scanning
      electron microscopy (SEM), which shows that the micelle/micelle membrane is
      sufficiently robust to withstand dissolution of the supporting template. Quartz
      crystal microbalance studies were conducted and provide good evidence that the
      micelle multilayer structure is retained after EDTA treatment. In addition, a
      hydrophobic dye was incorporated into the micelle cores prior to adsorption.
      After dissolution of the particle template, the resulting hollow capsules
      retained a high concentration of dye, suggesting that the core/shell structure of
      the micelles remains intact. Finally, thermogravimetric analysis (TGA) of dried
      capsules confirmed complete removal of the sacrificial inorganic template. As far
      as we are aware, this is the first demonstration of LbL assembled capsules
      composed entirely from responsive block copolymer micelles. The results presented
      here when combined with our previous findings demonstrate that such systems have
      potential application in the encapsulation and triggered release of actives.

PMID- 20052986
TI  - Artificial hairy surfaces with a nearly perfect hydrophobic response.
AB  - A nearly perfect hydrophobic interface by dint of mimicking hairs of arthropods
      was achieved for the first time. These Gamma-shape artificial hairs were made via
      a membrane casting technique on polypropylene substrates. This extreme
      hydrophobicity merely arises from microstructure modification, and no further
      chemical treatments are needed. The ultralow adhesion to water droplets was
      evaluated through video assessment, and it is believed to be attributed to the
      mechanical response of the artificial hairs. The principle of this fabrication
      technique is accessible and is expected to be compatible with large-area
      fabrication of superhydrophobic interfaces.

PMID- 20052987
TI  - Glutathione transferase A1-1: catalytic importance of arginine 15.
AB  - Glutathione transferases (GSTs) are fundamental enzymes of the cell
      detoxification system. They catalyze the nucleophilic attack of glutathione (GSH)
      on electrophilic substrates to produce less toxic compounds. The resulting
      substrate can then be recognized by ATP-dependent transmembrane pumps and
      consequently expelled from the cell. Despite all the existing studies on GSTs,
      many aspects of the catalytic events are still poorly understood. Recently, using
      as a model the GSTA1-1 enzyme, we proposed a GSH activation mechanism. Resorting
      to the density functional theory (DFT), we demonstrated that a water molecule
      could assist a proton transfer between the GSH thiol and alpha-carboxylic groups,
      after an initial conformational rearrangement of GSH, as evidenced by potential
      of mean force calculations. In this work to elucidate the catalytic role of
      Arg15, a strictly conserved active site residue in class alpha GSTs, we analyzed
      the activation energy barrier and structural details associated with the GSTA1-1
      mutants R15A, R15Repsilon,eta-c (an Arg residue with the epsilon,eta-nitrogens
      substituted by carbons), and R15Rneutral (a neutral Arg residue due to the a
      addition of a hydride in the zeta-carbon). A similar mechanism to the one used in
      our GSH activation proposal was implemented.

PMID- 20052988
TI  - Synthesis and anion affinity of a bidendate sulfonium fluorosilane Lewis acid.
AB  - The cationic fluorosilane [1-Ant(2)FSi-2-Me(2)S-(C(6)H(4))](+) (2(+)) readily
      complexes fluoride ions to afford the corresponding zwitterionic difluorosilicate
      complex 1-Ant(2)F(2)Si-2-Me(2)S-(C(6)H(4)) (2-F) with a binding constant in
      CHCl(3) of 7 (+/-1) x 10(6) M(-1). Structural and computational results indicate
      that the high fluorophilicity of 2(+) arises from both Coulombic and cooperative
      effects reflected by the formation of a Si-F-->S bridge with a F-->S distance of
      2.741(3) A.

PMID- 20052989
TI  - Synthesis of 2-substituted pyrazolo[1,5-a]pyridines through cascade direct
      alkenylation/cyclization reactions.
AB  - The synthesis of 2-substituted pyrazolo[1,5-a]pyridines from N-iminopyridinium
      ylides is described. These medicinally interesting compounds are formed through a
      cascade process involving a palladium-catalyzed direct alkenylation reaction
      followed by silver-mediated cyclization. The reaction can be performed with a
      wide range of electron-poor and electron-rich alkenyl iodides in good yields.
      This work represents perhaps the most direct route for the preparation of these
      compounds.

PMID- 20052990
TI  - Equating, or correction for between-block effects with application to body fluid
      LC-MS and NMR metabolomics data sets.
AB  - Combination of data sets from different objects (for example, from two groups of
      healthy volunteers from the same population) that were measured on a common set
      of variables (for example, metabolites or peptides) is desirable for statistical
      analysis in "omics" studies because it increases power. However, this type of
      combination is not directly possible if nonbiological systematic differences
      exist among the individual data sets, or "blocks". Such differences can, for
      example, be due to small analytical changes that are likely to accumulate over
      large time intervals between blocks of measurements. In this article we present a
      data transformation method, that we will refer to as "quantile equating", which
      per variable corrects for linear and nonlinear differences in distribution among
      blocks of semiquantitative data obtained with the same analytical method. We
      demonstrate the successful application of the quantile equating method to data
      obtained on two typical metabolomics platforms, i.e., liquid chromatography-mass
      spectrometry and nuclear magnetic resonance spectroscopy. We suggest uni- and
      multivariate methods to evaluate similarities and differences among data blocks
      before and after quantile equating. In conclusion, we have developed a method to
      correct for nonbiological systematic differences among semiquantitative data
      blocks and have demonstrated its successful application to metabolomics data
      sets.

PMID- 20052991
TI  - Third row transition metal hexafluorides, extraordinary oxidizers, and Lewis
      acids: electron affinities, fluoride affinities, and heats of formation of WF6,
      ReF6, OsF6, IrF6, PtF6, and AuF6.
AB  - High level electronic structure calculations were used to evaluate reliable, self
      consistent thermochemical data sets for the third row transition metal
      hexafluorides. The electron affinities, heats of formation, first (MF(6) -->
      MF(5) + F) and average M-F bond dissociation energies, and fluoride affinities of
      MF(6) (MF(6) + F(-) --> MF(7)(-)) and MF(5) (MF(5) + F(-) --> MF(6)(-)) were
      calculated. The electron affinities which are a direct measure for the oxidizer
      strength increase monotonically from WF(6) to AuF(6), with PtF(6) and AuF(6)
      being extremely powerful oxidizers. The inclusion of spin orbit corrections is
      necessary to obtain the correct qualitative order for the electron affinities.
      The calculated electron affinities increase with increasing atomic number, are in
      good agreement with the available experimental values, and are as follows: WF(6)
      (3.15 eV), ReF(6) (4.58 eV), OsF(6) (5.92 eV), IrF(6) (5.99 eV), PtF(6) (7.09
      eV), and AuF(6) (8.20 eV). A wide range of density functional theory exchange
      correlation functionals were also evaluated, and only three gave satisfactory
      results. The corresponding pentafluorides are extremely strong Lewis acids, with
      OsF(5), IrF(5), PtF(5), and AuF(5) significantly exceeding the acidity of SbF(5).
      The optimized geometries of the corresponding MF(7)(-) anions for W through Ir
      are classical MF(7)(-) anions with M-F bonds; however, for PtF(7)(-) and AuF(7)(
      ) non-classical anions were found with a very weak external F-F bond between an
      MF(6)(-) fragment and a fluorine atom. These two anions are text book examples
      for "superhalogens" and can serve as F atom sources under very mild conditions,
      explaining the ability of PtF(6) to convert NF(3) to NF(4)(+), ClF(5) to
      ClF(6)(+), and Xe to XeF(+) and why Bartlett failed to observe XePtF(6) as the
      reaction product of the PtF(6)/Xe reaction.

PMID- 20052992
TI  - Synthesis and properties of N7O+.
AB  - The reaction of NOF(2)(+)SbF(6)(-) with an equimolar amount of HN(3) in an
      anhydrous HF solution at -45 degrees C produces N(3)NOF(+)SbF(6)(-). When an
      excess of HN(3) is used in this reaction, N(7)O(+)SbF(6)(-) is formed. However,
      this compound could not be isolated as a solid and rapidly decomposed in a
      quantitative manner with N(2)O evolution to N(5)(+)SbF(6)(-). This reaction
      represents a novel and more convenient synthesis for N(5)(+)SbF(6)(-) because
      NOF(2)(+)SbF(6)(-) is more readily accessible than N(2)F(+)SbF(6)(-) and the
      N(5)(+) can be labeled in all five positions with (15)N by the simple use of
      terminally singly labeled N(3)(-). The formation of the N(7)O(+) cation was
      established by isotopic labeling experiments and theoretical calculations. It is
      shown that the addition of a second azido ligand to the same central atom allows
      the attack of the negatively charged Nalpha atom of one ligand by the positively
      charged Ngamma atom of the second ligand, thereby greatly lowering the activation
      energy barrier toward decomposition and explaining why geminal diazides are much
      less stable than either monoazides or vicinal diazides.

PMID- 20052993
TI  - Investigation of anticapsin biosynthesis reveals a four-enzyme pathway to
      tetrahydrotyrosine in Bacillus subtilis.
AB  - Bacillus subtilis produces the antibiotic anticapsin as an L-Ala-L-anticapsin
      dipeptide precursor known as bacilysin, whose synthesis is encoded by the bacA-D
      genes and the adjacent ywfGH genes. To evaluate the biosynthesis of the
      epoxycyclohexanone amino acid anticapsin from the primary metabolite prephenate,
      we have overproduced, purified, and characterized the activity of the BacA, BacB,
      YwfH, and YwfG proteins. BacA is an unusual prephenate decarboxylase that avoids
      the typical aromatization of the cyclohexadienol ring by protonating C(8) to
      produce an isomerized structure. BacB then catalyzes an allylic isomerization,
      generating a conjugated dienone with a 295 nm chromophore. Both the BacA and BacB
      products are regioisomers of H(2)HPP (dihydro-4-hydroxyphenylpyruvate). The BacB
      product is then a substrate for the short chain reductase YwfH which catalyzes
      the conjugate addition of hydride at the C(4) olefinic terminus using NADH to
      yield the cyclohexenol-containing tetrahydro-4-hydroxyphenylpyruvate H(4)HPP. In
      turn, this keto acid is a substrate for YwfG, which promotes transamination (with
      L-Phe as amino donor), to form tetrahydrotyrosine (H(4)Tyr). Thus BacA, BacB,
      YwfH, and YwfG act in sequence in a four enzyme pathway to make H(4)Tyr, which
      has not previously been identified in B. subtilis but is a recognized building
      block in cyanobacterial nonribosomal peptides such as micropeptins and
      aeruginopeptins.

PMID- 20052994
TI  - Exploring the roles of the metal ions in Escherichia coli copper amine oxidase.
AB  - To investigate the role of the active site copper in Escherichia coli copper
      amine oxidase (ECAO), we initiated a metal-substitution study. Copper
      reconstitution of ECAO (Cu-ECAO) restored only approximately 12% wild-type
      activity as measured by k(cat(amine)). Treatment with EDTA, to remove exogenous
      divalent metals, increased Cu-ECAO activity but reduced the activity of wild-type
      ECAO. Subsequent addition of calcium restored wild-type ECAO and further enhanced
      Cu-ECAO activities. Cobalt-reconstituted ECAO (Co-ECAO) showed lower but
      significant activity. These initial results are consistent with a direct electron
      transfer from TPQ to oxygen stabilized by the metal. If a Cu(I)-TPQ semiquinone
      mechanism operates, then an alternative outer-sphere electron transfer must also
      exist to account for the catalytic activity of Co-ECAO. The positive effect of
      calcium on ECAO activity led us to investigate the peripheral calcium binding
      sites of ECAO. Crystallographic analysis of wild-type ECAO structures, determined
      in the presence and absence of EDTA, confirmed that calcium is the normal ligand
      of these peripheral sites. The more solvent exposed calcium can be easily
      displaced by mono- and divalent cations with no effect on activity, whereas
      removal of the more buried calcium ion with EDTA resulted in a 60-90% reduction
      in ECAO activity and the presence of a lag phase, which could be overcome under
      oxygen saturation or by reoccupying the buried site with various divalent
      cations. Our studies indicate that binding of metal ions in the peripheral sites,
      while not essential, is important for maximal enzymatic activity in the mature
      enzyme.

PMID- 20052995
TI  - Blue light induces global and localized conformational changes in the kinase
      domain of full-length phototropin.
AB  - The blue-light photoreceptor phototropin plays a crucial role in optimizing
      photosynthesis in plants. In the two light-, oxygen-, or voltage-sensitive (LOV)
      domains of phototropin, the light stimulus is absorbed by the flavin
      chromophores. The signal is assumed to be transferred via dissociation and
      unfolding of a conserved J alpha helix element to the serine/threonine kinase
      domain. We investigated full-length phototropin from the green alga Chlamydomonas
      reinhardtii by Fourier transform infrared spectroscopy to shed light on the
      signal transfer within the protein and on the structural response of the kinase.
      Light-induced structural changes were assigned by comparing signals of the full
      length protein with those of the truncated LOV1-LOV2-J alpha and LOV1-LOV2 and
      with those of deletion mutants. A loss of helicity originating from the J alpha
      linker helix was observed in LOV1-LOV2-J alpha in agreement with previous studies
      of LOV2-J alpha. Full-length phototropin showed reversible global conformational
      changes via several turn elements. These changes were suppressed in a deletion
      mutant lacking the J alpha linker and are attributed to the kinase domain. The
      loss of turn structure is interpreted as a light-induced opening of the kinase
      tertiary structure upon release of the LOV2 domain. Concomitant protonation
      changes of Asp or Glu residues in the kinase domain were not observed. A light
      induced loss in helicity was observed only in the presence of a phototropin
      characteristic 54-amino acid extension of the kinase activation loop, which is
      predicted to be located apart from the catalytic cleft. This response of the
      extension might play a significant role in the phototropin signaling process.

PMID- 20052997
TI  - Effects of metal ions on entero-soluble poly(methacrylic acid-methyl
      methacrylate) coating: a combined analysis by ATR-FTIR spectroscopy and
      computational approaches.
AB  - Poly(methacrylic acid-methyl methacrylate)s (HPMMs) are pH-dependent polymers
      which ionize and form salts (PMMs) in neutral conditions. Despite their wide use
      in tablet coating, the interactions of PMMs with electrolytes present in
      biorelevant media and luminal fluids have been scantly investigated. The data
      generated in the current work provide the basic information on the effect of
      bivalent cations, namely, Ca2+, Zn2+ and Mn2+, on the HPMMs' solubility and,
      consequently, on the performances (disintegration and drug dissolution) of
      acetaminophen gastroresistant tablets when exposed to fluid containing such
      salts. The interactions between polymers and metal ions were analyzed by ATR-FTIR
      spectroscopy and in silico combining molecular dynamics simulations to explore
      the conformational profiles of several oligomers with different M(w), taken as
      model of the polymers, with ab initio and semiempirical calculations in the gas
      phase. The computational results agree with the experimental data in terms of
      spatial disposition of the bications with respect to PMMs (Ca2+ and Mn2+ as
      bidentate form and Zn2+ as monodentate ligand) and interaction strength (Zn2+ >
      Mn(2+) > Ca2+). The tablet disintegration and dissolution rate of acetaminophen
      were strongly affected by the interactions of the dissolving copolymer with the
      metal ions which led to coating insolubilization. These preliminary results
      underline that the ingestion of metal ions at high concentrations could affect
      the drug liberation from gastroresistant dosage forms.

PMID- 20052996
TI  - Characterization of a covalent polysulfane bridge in copper-zinc superoxide
      dismutase .
AB  - In the course of studies on human copper-zinc superoxide dismutase (SOD1), we
      observed a modified form of the protein whose mass was increased by 158 mass
      units. The covalent modification was characterized, and we established that it is
      a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1
      homodimer. The heptasulfane bridge was visualized directly in the crystal
      structure of a recombinant human mutant SOD1, H46R/H48Q, produced in yeast. The
      modification is reversible, with the bridge being cleaved by thiols, by cyanide,
      and by unfolding of the protein to expose the polysulfane. The polysulfane bridge
      can be introduced in vitro by incubation of purified SOD1 with elemental sulfur,
      even under anaerobic conditions and in the presence of a metal chelator. Because
      polysulfanes and polysulfides can catalyze the generation of reactive oxygen and
      sulfur species, the modification may endow SOD1 with a toxic gain of function.

PMID- 20052998
TI  - Secretomic and proteomic analysis of potential breast cancer markers by two
      dimensional differential gel electrophoresis.
AB  - The transformation of a normal cell into a cancer cell has been correlated with
      alterations in gene regulation and protein expression. To identify altered
      proteins and link them to the tumorigenesis of breast cancer, we have
      distinguished normal breast cells (MCF-10A) from noninvasive breast cancer cells
      (MCF-7) and invasive breast cancer cells (MB-MDA-231) to identify potential
      breast cancer markers in transformed breast cells. Using the 2D-DIGE and MALDI
      TOF MS techniques, we quantified and identified differentially expressed
      extracellular secreted proteins and total cellular proteins across MCF-7, MB-MDA
      231 and MCF-10A. The proteomic analysis of the secreted proteins identified 50
      unique differentially expressed proteins from three different media. In addition,
      133 unique differentially expressed proteins from total cellular proteins were
      also identified. Note that 14 of the secreted proteins and 51 of the total
      cellular proteins have not been previously reported in breast cancer research.
      Some of these unreported proteins have been examined in other breast cancer cell
      lines and have shown positive correlations with 2D-DIGE data. In summary, this
      study identifies numerous putative breast cancer markers from various stages of
      breast cancer. The results of this study may aid in developing proteins
      identified as useful diagnostic and therapeutic candidates in research on cancer
      and proteomics.

PMID- 20052999
TI  - Proteins deleterious on overexpression are associated with high intrinsic
      disorder, specific interaction domains, and low abundance.
AB  - In proteomics, there is a major challenge in how the functional significance of
      overexpressed proteins can be interpreted. This is particularly the case when
      examining proteins in cells or tissues. Here we have analyzed the physicochemical
      parameters, abundance level, half-life and degree of intrinsic disorder of
      proteins previously overexpressed in the yeast Saccharomyces cerevisiae. We also
      examined the interaction domains present and the manner in which overexpressed
      proteins are, or are not, associated with known complexes. We found a number of
      protein characteristics were strongly associated with deleterious phenotypes.
      These included protein abundance (where low-abundance proteins tend to be
      deleterious on overexpression), intrinsic disorder (where a striking association
      was seen between percent disorder and degree of deleterious effect), and the
      number of likely domain-domain interactions. Furthermore, we found a number of
      domain types, for example, DUF221 and the ubiquitin interaction motif, that were
      present predominantly in proteins that are deleterious on overexpression.
      Together, these results provide strong evidence that particular types of proteins
      are deleterious on overexpression whereas others are not. These factors can be
      considered in the interpretation of protein expression differences in proteomic
      experiments.

PMID- 20053000
TI  - SARANEA: a freely available program to mine structure-activity and structure
      selectivity relationship information in compound data sets.
AB  - We introduce SARANEA, an open-source Java application for interactive exploration
      of structure-activity relationship (SAR) and structure-selectivity relationship
      (SSR) information in compound sets of any source. SARANEA integrates various SAR
      and SSR analysis functions and utilizes a network-like similarity graph data
      structure for visualization. The program enables the systematic detection of
      activity and selectivity cliffs and corresponding key compounds across multiple
      targets. Advanced SAR analysis functions implemented in SARANEA include, among
      others, layered chemical neighborhood graphs, cliff indices, selectivity trees,
      editing functions for molecular networks and pathways, bioactivity summaries of
      key compounds, and markers for bioactive compounds having potential side effects.
      We report the application of SARANEA to identify SAR and SSR determinants in
      different sets of serine protease inhibitors. It is found that key compounds can
      influence SARs and SSRs in rather different ways. Such compounds and their
      SAR/SSR characteristics can be systematically identified and explored using
      SARANEA. The program and source code are made freely available under the GNU
      General Public License.

PMID- 20053001
TI  - Synthesis of peptide-protein conjugates using N-succinimidyl carbamate chemistry.
AB  - Peptide-protein conjugates are useful tools in different fields of research as,
      for instance, the development of vaccines and drugs or for studying biological
      mechanisms, to cite only few applications. N-Succinimidyl carbamate (NSC)
      chemistry has been scarcely used in this area. We show that unprotected peptides,
      featuring one lysine residue within their sequences, can be converted in good
      yield into NSC derivatives by reaction with disuccinimidylcarbonate (DSC). No
      hydrolysis of the NSC group was observed during RP-HPLC purification,
      lyophilization, or storage. NSC peptides reacted efficiently within minutes with
      lysozyme used as model protein. To illustrate usefulness of the method consisting
      of the synthesis of a peptide-protein conjugate of biological interest, a NSC
      peptide derived from a peptide substrate for tyrosylprotein sulfotransferase (TS)
      was synthesized and ligated to receptor-binding nontoxic B-subunit of Shiga toxin
      (STxB). Immunofluorescence studies showed the intracellular delivery of the TS
      STxB conjugate and its ability to circulate to the Golgi as the native STxB
      protein. Moreover, we demonstrate that the TS label could be sulfated by
      tyrosylprotein sulfotransferases present in the Golgi. Thus, NSC chemistry
      permitted rapid synthesis of a peptide-protein conjugate worthwhile for studying
      the transport of proteins from the plasma membrane to the Golgi. The second part
      of this article describes a more general method for synthesizing peptide-protein
      conjugates without any limitation of the peptide sequence. The conjugates were
      assembled by combining NSC chemistry and alpha-oxo semicarbazone ligation. To
      this end, a glyoxylyl NSC peptide was synthesized and reacted with lysozyme. The
      glyoxylyl groups on the protein were then reacted with a semicarbazide peptide to
      produce the target peptide-protein conjugate. Both reactions, namely, urea bond
      formation and alpha-oxo semicarbazone ligation, were carried at pH 8.0 using a
      one-pot procedure.

PMID- 20053002
TI  - Testing a series of causal propositions relating time in child care to children's
      externalizing behavior.
AB  - Prior research has documented associations between hours in child care and
      children's externalizing behavior. A series of longitudinal analyses were
      conducted to address 5 propositions, each testing the hypothesis that child care
      hours causes externalizing behavior. Data from the National Institute of Child
      Health and Human Development Early Child Care Research Network (NICHD) Study of
      Early Child Care and Youth Development were used in this investigation because
      they include repeated measures of child care experiences, externalizing behavior,
      and family characteristics. There were 3 main findings. First, the evidence
      linking child care hours with externalizing behavior was equivocal in that
      results varied across model specifications. Second, the association between child
      care hours and externalizing behavior was not due to a child effect. Third, child
      care quality and proportion of time spent with a large group of peers moderated
      the effects of child care hours on externalizing behavior. The number of hours
      spent in child care was more strongly related to externalizing behavior when
      children were in low-quality child care and when children spent a greater
      proportion of time with a large group of peers. The magnitude of associations
      between child care hours and externalizing behavior was modest. Implications are
      that parents and policymakers must take into account that externalizing behavior
      is predicted from a constellation of variables in multiple contexts.

PMID- 20053003
TI  - Gender-role attitudes and behavior across the transition to parenthood.
AB  - On the basis of social structural theory and identity theory, the current study
      examined changes in gender-role attitudes and behavior across the first-time
      transition to parenthood and following the birth of a second child for
      experienced mothers and fathers. Data were analyzed from the ongoing longitudinal
      Wisconsin Study of Families and Work. Gender-role attitudes, work and family
      identity salience, and division of household labor were measured for 205 first
      time and 198 experienced mothers and fathers across 4 time points from 5 months
      pregnant to 12 months postpartum. Multilevel latent growth curve analysis was
      used to analyze the data. In general, parents became more traditional in their
      gender-role attitudes and behavior following the birth of a child, women changed
      more than men, and first-time parents changed more than experienced parents.
      Findings suggest that changes in gender-role attitudes and behavior following the
      birth of a child may be attributed to both the process of transitioning to
      parenthood for the first time and that of negotiating the demands of having a new
      baby in the family. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053004
TI  - Analyzing true change in longitudinal multitrait-multimethod studies: application
      of a multimethod change model to depression and anxiety in children.
AB  - The authors show how structural equation modeling can be applied to analyze
      change in longitudinal multitrait-multimethod (MTMM) studies. For this purpose,
      an extension of latent difference models (McArdle, 1988; Steyer, Eid, &
      Schwenkmezger, 1997) to multiple constructs and multiple methods is presented.
      The model allows investigators to separate true change from measurement error and
      to analyze change simultaneously for different methods. The authors also show how
      Campbell and Fiske's (1959) guidelines for analyzing convergent and discriminant
      validity can be applied to the measurement of latent change. The practical
      application of the multimethod change model is illustrated in a reanalysis of
      child depression and anxiety scores (N = 906 American children) that were
      assessed by self- and parent reports on three measurement occasions. The analyses
      revealed that (a) the convergent validity of change was low for both constructs
      and (b) sex was a significant predictor of self-reported, but not of parent
      reported, anxiety states. Finally, the authors discuss advantages and limitations
      and compare the model with other approaches for analyzing longitudinal MTMM data.

PMID- 20053005
TI  - Adolescent peer relationships and behavior problems predict young adults'
      communication on social networking websites.
AB  - This study examined online communication on social networking web pages in a
      longitudinal sample of 92 youths (39 male, 53 female). Participants' social and
      behavioral adjustment was assessed when they were ages 13-14 years and again at
      ages 20-22 years. At ages 20-22 years, participants' social networking website
      use and indicators of friendship quality on their web pages were coded by
      observers. Results suggested that youths who had been better adjusted at ages 13
      14 years were more likely to be using social networking web pages at ages 20-22
      years, after statistically controlling for age, gender, ethnicity, and parental
      income. Overall, youths' patterns of peer relationships, friendship quality, and
      behavioral adjustment at ages 13-14 years and at ages 20-22 years predicted
      similar qualities of interaction and problem behavior on their social networking
      websites at ages 20-22 years. Findings are consistent with developmental theory
      asserting that youths display cross-situational continuity in their social
      behaviors and suggest that the conceptualization of continuity may be extended
      into the online domain.

PMID- 20053006
TI  - Learning the rules: observation and imitation of a sorting strategy by 36-month
      old children.
AB  - Two experiments were used to investigate the scope of imitation by testing
      whether 36-month-olds can learn to produce a categorization strategy through
      observation. After witnessing an adult sort a set of objects by a visible
      property (their color; Experiment 1) or a nonvisible property (the particular
      sounds produced when the objects were shaken; Experiment 2), children showed
      significantly more sorting by those dimensions relative to children in control
      groups, including a control in which children saw the sorted endstate but not the
      intentional sorting demonstration. The results show that 36-month-olds can do
      more than imitate the literal behaviors they see; they also abstract and imitate
      rules that they see another person use.

PMID- 20053007
TI  - Infant perception of audio-visual speech synchrony.
AB  - Three experiments investigated perception of audio-visual (A-V) speech synchrony
      in 4- to 10-month-old infants. Experiments 1 and 2 used a convergent-operations
      approach by habituating infants to an audiovisually synchronous syllable
      (Experiment 1) and then testing for detection of increasing degrees of A-V
      asynchrony (366, 500, and 666 ms) or by habituating infants to a detectably
      asynchronous syllable (666 ms; Experiment 2) and then testing for detection of
      decreasing degrees of asynchrony (500, 366, and 0 ms). Following habituation to
      the synchronous syllable, infants detected only the largest A-V asynchrony (0 ms
      vs. 666 ms), whereas following habituation to the asynchronous syllable, infants
      detected the largest asynchrony (666 ms vs. 0 ms) as well as a smaller one (666
      ms vs. 366 ms). Experiment 3 investigated the underlying mechanism of A-V
      asynchrony detection and indicated that responsiveness was based on a sensitivity
      to stimulus-energy onsets rather than the dynamic correlation between acoustic
      and visible utterance attributes. These findings demonstrated that infant
      perception of A-V speech synchrony is subject to the effects of short-term
      experience and that it is driven by a low-level, domain-general mechanism.

PMID- 20053008
TI  - A new look at children's understanding of mind and emotion: the case of prayer.
AB  - Multiple methods were used to examine children's awareness of connections between
      emotion and prayer. Four-, 6-, and 8-year-olds and adults (N = 100) predicted
      whether people would pray when feeling different emotions, explained why
      characters in different situations decided to pray, and predicted whether
      characters' emotions would change after praying. Four- and 6-year-olds
      exclusively judged that positive emotions motivate prayer, whereas 8-year-olds
      and adults most often predicted that negative emotions would cause people to pray
      and that praying could improve emotions. There was also a significant increase
      between 4 and 8 years in explaining prayer as motivated by need for assistance,
      for thanksgiving, and for conversation, as well as for explaining postprayer
      emotions in relation to God or prayer. Religious background predicted individual
      differences in reasoning only for 4-year-olds.

PMID- 20053009
TI  - Global-local and trail-making tasks by monolingual and bilingual children: beyond
      inhibition.
AB  - In 3 experiments, a total of 151 monolingual and bilingual 6-year-old children
      performed similarly on measures of language and cognitive ability; however,
      bilinguals solved the global-local and trail-making tasks more rapidly than
      monolinguals. This bilingual advantage was found not only for the traditionally
      demanding conditions (incongruent global-local trials and Trails B) but also for
      the conditions not usually considered to be cognitively demanding (congruent
      global-local trials and Trails A). All the children performed similarly when
      congruent trials were presented in a single block or when perceptually simple
      stimuli were used, ruling out speed differences between the groups. The results
      demonstrate a bilingual advantage in processing complex stimuli in tasks that
      require executive processing components for conflict resolution, including
      switching and updating, even when no inhibition appears to be involved. They also
      suggest that simple conditions of the trail-making and global-local tasks involve
      some level of effortful processing for young children. Finally, the bilingual
      advantage in the trail-making task suggests that the interpretation of
      standardized measures of executive control needs to be reconsidered for children
      with specific experiences, such as bilingualism.

PMID- 20053010
TI  - Discrimination of phonemic vowel length by Japanese infants.
AB  - Japanese has a vowel duration contrast as one component of its language-specific
      phonemic repertory to distinguish word meanings. It is not clear, however, how a
      sensitivity to vowel duration can develop in a linguistic context. In the present
      study, using the visual habituation-dishabituation method, the authors evaluated
      infants' abilities to discriminate Japanese long and short vowels embedded in two
      syllable words (/mana/ vs. /ma:na/). The results revealed that 4-month-old
      Japanese infants (n = 32) failed to discriminate the contrast (p = .676), whereas
      9.5-month-olds (n = 33) showed the discrimination ability (p = .014). The 7.5
      month-olds did not show positive evidence to discriminate the contrast either
      when the edited stimuli were used (n = 33; p = .275) or when naturally uttered
      stimuli were used (n = 33; p = .189). By contrast, the 4-month-olds (n = 24)
      showed sensitivity to a vowel quality change (/mana/ vs. /mina/; p = .034). These
      results indicate that Japanese infants acquire sensitivity to long-short vowel
      contrasts between 7.5 and 9.5 months of age and that the developmental course of
      the phonemic category by the durational changes is different from that by the
      quality change.

PMID- 20053011
TI  - The development of reproductive strategy in females: early maternal harshness -->
      earlier menarche --> increased sexual risk taking.
AB  - To test a proposition central to J. Belsky, L. Steinberg, and P. Draper's (1991)
      evolutionary theory of socialization-that pubertal maturation plays a role in
      linking early rearing experience with adolescent sexual risk taking (i.e.,
      frequency of sexual behavior) and, perhaps, other risk taking (e.g., alcohol,
      drugs, delinquency)-the authors subjected longitudinal data on 433 White, 62
      Black, and 31 Hispanic females to path analysis. Results showed (a) that greater
      maternal harshness at 54 months predicted earlier age of menarche; (b) that
      earlier age of menarche predicted greater sexual (but not other) risk taking; and
      (c) that maternal harshness exerted a significant indirect effect, via earlier
      menarche, on sexual risk taking (i.e., greater harshness --> earlier menarche -->
      greater sexual risk taking) but only a direct effect on other risk taking.
      Results are discussed in terms of evolutionary perspectives on human development
      and reproductive strategy, and future directions for research are outlined.

PMID- 20053013
TI  - A longitudinal study of conversations with parents about sex and dating during
      college.
AB  - Emerging adulthood is a time of sexual and romantic relationship development as
      well as change in the parent-child relationship. This study provides a
      longitudinal analysis of 30 young adults' (17 women, 13 men) sexual experiences,
      attitudes about sexuality and dating, and reported conversations with parents
      about sexuality and dating from the 1st and 4th years of college. Self-report
      questionnaires revealed increases in general closeness with parents, increases in
      sexual and dating experiences, and more sexually permissive as well as more
      gender stereotyped attitudes. Qualitative analyses of individual interviews
      indicated a movement from unilateral and restrictive sex-based topics to more
      reciprocal and relationship-focused conversations over time. Gender analyses
      revealed that young women reported more restrictive sex messages and young men
      more positive sex messages. Participants also described increased openness and
      comfort in talking about sexual topics with both mothers and fathers from the 1st
      to 4th year of college. Overall, the results suggest that prior findings of
      increased mutuality with parents during the college years extend to the
      traditionally taboo topic of sexuality.

PMID- 20053012
TI  - Systems in development: motor skill acquisition facilitates three-dimensional
      object completion.
AB  - How do infants learn to perceive the backs of objects that they see only from a
      limited viewpoint? Infants' 3-dimensional object completion abilities emerge in
      conjunction with developing motor skills--independent sitting and visual-manual
      exploration. Infants at 4.5 to 7.5 months of age (n = 28) were habituated to a
      limited-view object and tested with volumetrically complete and incomplete
      (hollow) versions of the same object. Parents reported infants' sitting
      experience, and infants' visual-manual exploration of objects was observed in a
      structured play session. Infants' self-sitting experience and visual-manual
      exploratory skills predicted looking at the novel, incomplete object on the
      habituation task. Further analyses revealed that self-sitting facilitated
      infants' visual inspection of objects while they manipulated them. The results
      are framed within a developmental systems approach, wherein infants' sitting
      skill, multimodal object exploration, and object knowledge are linked in
      developmental time.

PMID- 20053014
TI  - Early childhood family structure and mother-child interactions: variation by race
      and ethnicity.
AB  - With data from the Early Childhood Longitudinal Study-Birth Cohort (n = 6,449), a
      nationally representative sample of births in 2001, we used hierarchical linear
      modeling to analyze differences in observed interactions between married,
      cohabiting, never-married, and divorced mothers and their children. In contrast
      to previous studies, we concentrated on early childhood, a developmentally
      critical period that has been understudied in the family structure literature,
      and relied on objective observational measures of mother-child interactions,
      which are unlikely to be biased by maternal perceptions of interactions with
      children. Nonmarital family structures were common in the lives of young
      children, as 32% lived outside of a married, biological parent home. Initial
      results indicated that married families were consistently associated with higher
      quality interactions. Moreover, though it was hypothesized that the presence of a
      biological father might be associated with higher quality interactions than
      single-parent households, this hypothesis was not confirmed. Additional models
      suggest that race and ethnicity moderated the effect of family structure, as non
      Hispanic Black and non-Hispanic White participants showed little significant
      variation between married and unmarried families. Among Hispanics, mothers living
      in cohabiting, divorced, or single families, when compared to married mothers,
      exhibited more negative and more intrusive behaviors; cohabiting mothers also
      scored lower on the measure of cognitive stimulation. Results suggest that
      marriage may not be uniformly associated with higher levels of mother-child
      interactions and that cohabitation, particularly for Hispanics, may be associated
      with adverse outcomes.

PMID- 20053015
TI  - Children's response to adult disgust elicitors: development and acquisition.
AB  - Little is known about when or how different disgust elicitors are acquired. In
      Study 1, parents of children (0-18 years old) rated how their child would react
      to 22 disgust elicitors. Different developmental patterns were identified for
      core, animal, and sociomoral elicitors, with core elicitors emerging first. In
      Study 2, children (2-16 years old) were exposed alone and then with their parent
      to a range of elicitors derived from Study 1. Self-report, behavioral, and facial
      expression data were obtained along with measures of contagion, conservation, and
      contamination. Convergent evidence supported the developmental patterns reported
      in Study 1. Evidence for parent-child transmission was also observed, with
      parents of young children emoting more disgust to their offspring and showing
      greater behavioral avoidance. Moreover, child reactivity to animal and sociomoral
      elicitors and contamination correlated with parental responsiveness. Finally,
      young children who failed to demonstrate contagion and conservation knowledge
      were as reactive to core elicitors and contamination as children of the same age
      who demonstrated such knowledge. These findings are interpreted within an
      evolutionary framework in which core disgust responses are acquired early to
      promote avoidance of pathogens.

PMID- 20053016
TI  - The developmental relations between conceptual and procedural knowledge: a
      multimethod approach.
AB  - Interactions between conceptual and procedural knowledge influence the
      development of mathematical competencies. However, after decades of research,
      these interrelations are still under debate, and empirical results are
      inconclusive. The authors point out a source of these problems. Different kinds
      of knowledge and competencies only show up intertwined in behavior, making it
      hard to measure them validly and independently of each other. A multimethod
      approach was used to investigate the extent of these problems. A total of 289
      fifth and sixth graders' conceptual and procedural knowledge about decimal
      fractions was measured by 4 common hypothetical measures of each kind of
      knowledge. Study 1 tested whether treatments affected the 2 groups of measures in
      consistent ways. Study 2 assessed, across 3 measurement points, whether
      conceptual and procedural knowledge could be modeled as latent factors underlying
      the measures. The results reveal substantial problems with the validities of the
      measures, which might have been present but gone undetected in previous studies.
      A solution to these problems is essential for theoretical and practical progress
      in the field. The potential of the multimethod approach for this enterprise is
      discussed.

PMID- 20053017
TI  - Age differences in affective decision making as indexed by performance on the
      Iowa Gambling Task.
AB  - Contemporary perspectives on age differences in risk taking, informed by advances
      in developmental neuroscience, have emphasized the need to examine the ways in
      which emotional and cognitive factors interact to influence decision making. In
      the present study, a diverse sample of 901 individuals between the ages of 10 and
      30 were administered a modified version of the Iowa Gambling Task, which is
      designed to measure affective decision making. Results indicate that approach
      behaviors (operationalized as the tendency to play increasingly from the
      advantageous decks over the course of the task) display an inverted U-shape
      relation to age, peaking in mid- to late adolescence. In contrast, avoidance
      behaviors (operationalized as the tendency to refrain from playing from the
      disadvantageous decks) increase linearly with age, with adults avoiding
      disadvantageous decks at higher rates than both preadolescents and adolescents.
      The finding that adolescents, compared to adults, are relatively more approach
      oriented in response to positive feedback and less avoidant in response to
      negative feedback is consistent with recent studies of brain development, as well
      as epidemiological data on various types of risky behavior, and may have
      important practical implications for the prevention of adolescent risk taking.

PMID- 20053018
TI  - Narrative and ethnic identity exploration: a longitudinal account of emerging
      adults' ethnicity-related experiences.
AB  - The purpose in this longitudinal study was to investigate further the link
      between ethnic identity processes and content through an examination of emerging
      adults' narratives of ethnicity-related experiences. Seventy ethnically diverse
      college students completed an ethnic identity exploration index and told an
      ethnicity-related narrative on 2 occasions 18 months apart. Results indicated
      that (a) participants who increased in exploration over time were more likely to
      change their narrative theme than participants who decreased or remained stable
      in exploration and (b) these changes were more likely to be to stories of
      experience of prejudice or connection to culture. This study highlights the costs
      and benefits of ethnic identity and provides evidence for a linkage between
      ethnic identity process and content in emerging adulthood.

PMID- 20053019
TI  - Do children profit from looking beyond looks? From similarity-based to cue
      abstraction processes in multiple-cue judgment.
AB  - The authors investigated the ability of 9- to 11-year-olds and of adults to use
      similarity-based and rule-based processes as a function of task characteristics
      in a task that can be considered either a categorization task or a multiple-cue
      judgment task, depending on the nature of the criterion (binary vs. continuous).
      Both children and adults relied on similarity-based processes in the
      categorization task. However, adults relied on cue abstraction in the multiple
      cue judgment task, whereas the majority of children continued to rely on
      similarity-based processes. Reliance on cue abstraction resulted in better
      judgments for adults but not for children in the multiple-cue judgment task. This
      suggests that 9- to 11-year-olds may have defaulted to similarity-based processes
      because they were not able to employ a cue abstraction process efficiently.

PMID- 20053021
TI  - Where self-control comes from: on the development of self-control and its
      relationship to deviance over time.
AB  - The current study tested a set of interrelated theoretical propositions based on
      self-control theory (M. R. Gottfredson & T. Hirschi 1990). Data were collected on
      1,155 children at 4.5 years, at 8.5 years (3rd grade), and at 10.5 years (5th
      grade) as part of the National Institute of Child Health and Human Development
      longitudinal study over a 6-year period. Findings based on simple structural
      equation models and latent growth modeling of developmental trajectories suggest
      that (a) there was great construct stability of self-control and deviance over
      the 6-year period, (b) there was positive growth in self-control trajectory over
      time, (c) parenting predicted this trajectory but also explained variability in
      self-control at initial status, (d) there was a declining deviance trajectory
      over time, (e) self-control at initial status reduced the unexplained deviance
      variance by 44.8%, and (f) both the intercept and slope factors shared about 75%
      of the variance based on growth-to-growth curve predictive models of self-control
      and deviance. Findings are discussed in terms of their implications for self
      control theory and future empirical work.

PMID- 20053020
TI  - The cognitive processes underlying event-based prospective memory in school-age
      children and young adults: a formal model-based study.
AB  - Fifty children 7 years of age (29 girls, 21 boys), 53 children 10 years of age
      (29 girls, 24 boys), and 36 young adults (19 women, 17 men) performed a
      computerized event-based prospective memory task. All 3 groups differed
      significantly in prospective memory performance, with adults showing the best
      performance and with 7-year-olds showing the poorest performance. We used a
      formal multinomial process tree model of event-based prospective memory to
      decompose age differences in cognitive processes that jointly contribute to
      prospective memory performance. The formal modeling results demonstrate that
      adults differed significantly from the 7-year-olds and the 10-year-olds on both
      the prospective component and the retrospective component of the task. The 7-year
      olds and the 10-year-olds differed only in the ability to recognize prospective
      memory target events. The prospective memory task imposed a cost to ongoing
      activities in all 3 age groups.

PMID- 20053022
TI  - Adolescents' occupational and educational aspirations and expectations: links to
      high school activities and adult educational attainment.
AB  - This longitudinal study explored adolescents' future-oriented cognitions, current
      activities, and later educational attainment using data from 317 adolescents (55%
      female; mean age = 14.98 years, SD = 0.85) followed into early adulthood.
      Aspirations and expectations regarding work and education showed modest stability
      from year to year. Exploration of the reciprocal relations between these
      cognitions and adolescents' activities supported both unidirectional and
      bidirectional effects, with different patterns emerging for aspirations and
      expectations. In multiple regression analyses, future-oriented cognitions
      predicted adult educational attainment; follow-up analyses indicated that the
      effect of adolescents' expectations was partially mediated by participation in
      extracurricular activities. These results suggest a potentially important
      influence of adolescents' future-oriented cognitions on their current behavior
      and future attainments.

PMID- 20053023
TI  - Development of intuitions about support beyond infancy.
AB  - In a series of 3 experiments modeled after infant studies, 3- to- 6-year-old
      children's intuitive knowledge about support was assessed. Different objects were
      shown either sufficiently supported or not. Children had to predict whether a
      block would remain standing on a platform upon release or make perceptual
      judgments about the possibility of a shown block-on-platform configuration.
      Overall, performance was strongly age-related and independent of task context.
      Sensitivity for the amount of contact between object and support was clearly
      evidenced for each of the age-groups tested and was almost perfect in 5- and 6
      year-olds. By contrast, sensitivity for the proportion of an object's volume
      positioned over the support was only marginally reliable in 3-year-olds and still
      far from perfect in 6-year-olds. It is concluded that basic intuitions about
      support undergo distinct developmental change beyond infancy and are not yet
      fully developed in kindergartners.

PMID- 20053024
TI  - Exploring developmental differences in visual short-term memory and working
      memory.
AB  - Although visuospatial short-term memory tasks have been found to engage more
      executive resources than do their phonological counterparts, it remains unclear
      whether this is due to intrinsic differences between the tasks or differences in
      participants' experience with them. The authors found 11-year-olds' performances
      on both visual short-term and working memory tasks to be more greatly impaired by
      an executive suppression task (random number generation) than were those of 8
      year-olds. Similar findings with adults (e.g., Kane & Engle, 2000) suggest that
      the imposition of a suppression task may have overloaded the older children's
      executive resources, which would otherwise be used for deploying strategies for
      performing the primary tasks. Conversely, the younger children, who probably
      never had the capacity or know-how to engage these facilitative strategies in the
      first place, performed more poorly in the single task condition but were less
      affected in the dual task condition. These findings suggest that differences in
      the children's ability to deploy task-relevant strategy are likely to account for
      at least part of the executive resource requirements of visual memory tasks.

PMID- 20053025
TI  - Infants prefer the musical meter of their own culture: a cross-cultural
      comparison.
AB  - Infants prefer native structures such as familiar faces and languages. Music is a
      universal human activity containing structures that vary cross-culturally. For
      example, Western music has temporally regular metric structures, whereas music of
      the Balkans (e.g., Bulgaria, Macedonia, Turkey) can have both regular and
      irregular structures. We presented 4- to 8-month-old American and Turkish infants
      with contrasting melodies to determine whether cultural background would
      influence their preferences for musical meter. In Experiment 1, American infants
      preferred Western over Balkan meter, whereas Turkish infants, who were familiar
      with both Western and Balkan meters, exhibited no preference. Experiments 2 and 3
      presented infants with either a Western or Balkan meter paired with an arbitrary
      rhythm with complex ratios not common to any musical culture. Both Turkish and
      American infants preferred Western and Balkan meter to an arbitrary meter.
      Infants' musical preferences appear to be driven by culture-specific experience
      and a culture-general preference for simplicity.

PMID- 20053026
TI  - Gender differences in keeping secrets from parents in adolescence.
AB  - The current longitudinal study examined adolescent gender differences in the
      developmental changes and relational correlates of secrecy from parents. For 4
      successive years, starting in the second year of junior high (mean age at Time 1
      = 13.2 years, SD = 0.51), 149 male and 160 female Dutch adolescents reported on
      secrecy from their parents and the quality of the parent-child relationship.
      Latent growth curve modeling revealed a linear increase in secrecy, which was
      significantly faster for boys than for girls. Moreover, cross-lagged panel
      analyses showed clear concurrent and longitudinal linkages between secrecy from
      parents and poorer parent-child relationship quality in girls. In boys, much less
      strong linkages were found between poorer relationships and secrecy from parents.

PMID- 20053027
TI  - Polling the face: prediction and consensus across cultures.
AB  - Previous work has shown that individuals agree across cultures on the traits that
      they infer from faces. Previous work has also shown that inferences from faces
      can be predictive of important outcomes within cultures. The current research
      merges these two lines of work. In a series of cross-cultural studies, the
      authors asked American and Japanese participants to provide naive inferences of
      traits from the faces of U.S. political candidates (Studies 1 and 3) and Japanese
      political candidates (Studies 2 and 4). Perceivers showed high agreement in their
      ratings of the faces, regardless of culture, and both sets of judgments were
      predictive of an important ecological outcome (the percentage of votes that each
      candidate received in the actual election). The traits predicting electoral
      success differed, however, depending on the targets' culture. Thus, when American
      and Japanese participants were asked to provide explicit inferences of how likely
      each candidate would be to win an election (Studies 3-4), judgments were
      predictive only for same-culture candidates. Attempts to infer the electoral
      success for the foreign culture showed evidence of self-projection. Therefore,
      perceivers can reliably infer predictive information from faces but require
      knowledge about the target's culture to make these predictions accurately.

PMID- 20053028
TI  - The influence of information processing goal pursuit on postdecision affect and
      behavioral intentions.
AB  - Two important forces in human behavior are action and inaction. Although action
      and inaction are commonly associated with the presence and the absence of
      behavioral activity, they can also be represented as information processing
      goals. Action (inaction) goals influence decision effort and increase
      satisfaction with environments that are structured to allow for more (less)
      processing (Studies 1 and 2). This increased satisfaction can transfer to the
      decision (Study 3) and can increase the intent to perform a decision-congruent
      behavior (Studies 4 and 6). Finally, the author shows escalation of action and
      inaction goals when they are not achieved (Study 5) and rebound of the
      alternative goal when the focal goal is achieved (Study 6).

PMID- 20053029
TI  - When perception is more than reality: the effects of perceived versus actual
      resource depletion on self-regulatory behavior.
AB  - Considerable research demonstrates that the depletion of self-regulatory
      resources impairs performance on subsequent tasks that demand these resources.
      The current research sought to assess the impact of perceived resource depletion
      on subsequent task performance at both high and low levels of actual depletion.
      The authors manipulated perceived resource depletion by having participants 1st
      complete a depleting or nondepleting task before being presented with feedback
      that did or did not provide a situational attribution for their internal state.
      Participants then persisted at a problem-solving task (Experiments 1-2),
      completed an attention-regulation task (Experiment 3), or responded to a
      persuasive message (Experiment 4). The findings consistently demonstrated that
      individuals who perceived themselves as less (vs. more) depleted, whether high or
      low in actual depletion, were more successful at subsequent self-regulation.
      Thus, perceived regulatory depletion can impact subsequent task performance-and
      this impact can be independent of one's actual state of depletion.

PMID- 20053030
TI  - Effects of a supportive or an unsupportive audience on biological and
      psychological responses to stress.
AB  - Although social support is related to substantial benefits for health and well
      being, research has uncovered qualifications to its benefits. In a test of the
      psychological and biological impact of an audience on responses to laboratory
      stress challenges, 183 participants going through the Trier Social Stress Test
      experienced either (a) an unsupportive audience, (b) a supportive audience, or
      (c) no audience. Both audience conditions produced significantly stronger
      cortisol, heart rate, and blood pressure responses to the stress tasks, relative
      to the no-audience control, even though the supportive audience was rated as
      supportive. Contrary to hypotheses offered by several theories, these effects
      were not moderated by self-esteem, individual differences in psychological
      resources, or baseline social support. Psychological resources and baseline
      social support were, however, tied to more beneficial biological and
      psychological profiles at baseline and at recovery in some cases. It was
      concluded that when one must perform stressful tasks in front of an audience,
      evaluative concerns may outweigh the potential benefits of a supportive audience.

PMID- 20053033
TI  - Significant others and contingencies of self-worth: activation and consequences
      of relationship-specific contingencies of self-worth.
AB  - Three studies tested the activation and consequences of contingencies of self
      worth associated with specific significant others, that is, relationship-specific
      contingencies of self-worth. The results showed that activating the mental
      representation of a significant other with whom one strongly desires closeness
      led participants to stake their self-esteem in domains in which the significant
      other wanted them to excel. This was shown in terms of self-reported
      contingencies of self-worth (Study 1), in terms of self-worth after receiving
      feedback on a successful or unsatisfactory performance in a relationship-specific
      contingency domain (Study 2), and in terms of feelings of reduced self-worth
      after thinking about a failure in a relationship-specific contingency domain
      (Study 3). Across studies, a variety of contingency domains were examined.
      Furthermore, Study 3 showed that failing in an activated relationship-specific
      contingency domain had negative implications for current feelings of closeness
      and acceptance in the significant-other relationship. Overall, the findings
      suggest that people's contingencies of self-worth depend on the social situation
      and that performance in relationship-specific contingency domains can influence
      people's perceptions of their relationships.

PMID- 20053031
TI  - Relationship influences on exploration in adulthood: the characteristics and
      function of a secure base.
AB  - This investigation advances theory and research regarding relationship influences
      on exploration in adulthood. This is accomplished by (a) identifying important
      characteristics of a secure base, (b) examining the influence of the presence or
      absence of these characteristics on exploration behavior in adulthood, and (c)
      identifying individual-difference factors that are predictive of the provision
      and receipt of secure base support. In 2 sessions, married couples (N = 167)
      provided reports of relationship dynamics involving exploration, and they
      participated in an exploration activity that was videotaped and coded by
      independent observers. Results indicated that the 3 identified characteristics of
      a secure base (availability, noninterference, and encouragement) are strongly
      predictive of exploration behavior, and that the provision and receipt of these
      behaviors can be predicted by individual differences in attachment. Implications
      of results and contributions to existing literature are discussed.

PMID- 20053034
TI  - For better or worse? Coregulation of couples' cortisol levels and mood states.
AB  - Although a majority of adults live with a close relationship partner, little is
      known about whether and how partners' momentary affect and physiology covary, or
      "coregulate." This study used a dyadic multilevel modeling approach to explore
      the coregulation of spouses' mood states and cortisol levels in 30 married
      couples who sampled saliva and reported on mood states 4 times per day for 3
      days. For both husbands and wives, own cortisol level was positively associated
      with partner's cortisol level, even after sampling time was controlled. For
      wives, marital satisfaction weakened the strength of this effect. Partner's
      negative mood was positively associated with own negative mood for both husbands
      and wives. Marital satisfaction fully moderated this effect, reducing the
      strength of the association between one's own and one's partner's negative mood
      states. Spouses' positive moods were not correlated. As expected, within-couple
      coregulation coefficients were stronger when mood and cortisol were sampled in
      the early morning and evening, when spouses were together at home, than during
      the workday. The results suggest that spouses' fluctuations in negative mood and
      cortisol levels are linked over several days and that marital satisfaction may
      buffer spouses from their partners' negative mood or stress state.

PMID- 20053036
TI  - From what might have been to what must have been: counterfactual thinking creates
      meaning.
AB  - Four experiments explored whether 2 uniquely human characteristics-counterfactual
      thinking (imagining alternatives to the past) and the fundamental drive to create
      meaning in life-are causally related. Rather than implying a random quality to
      life, the authors hypothesized and found that counterfactual thinking heightens
      the meaningfulness of key life experiences. Reflecting on alternative pathways to
      pivotal turning points even produced greater meaning than directly reflecting on
      the meaning of the event itself. Fate perceptions ("it was meant to be") and
      benefit-finding (recognition of positive consequences) were identified as
      independent causal links between counterfactual thinking and the construction of
      meaning. Through counterfactual reflection, the upsides to reality are
      identified, a belief in fate emerges, and ultimately more meaning is derived from
      important life events.

PMID- 20053037
TI  - What it takes to forgive: When and why executive functioning facilitates
      forgiveness.
AB  - To establish what it takes to forgive, the present research focused on the
      cognitive underpinnings of the forgiveness process. We conducted four studies
      that examined and supported the prediction that executive functioning (a set of
      cognitive control processes) facilitates forgiveness. First, a correlational
      study revealed a positive relation between executive functioning and
      dispositional forgiveness (Study 1). Second, a longitudinal study demonstrated
      that executive functioning predicts the development of forgiveness over a period
      of 5 weeks after the offense (Study 2). Finally, two experiments examined when
      and why executive functioning facilitates forgiveness. Specifically, and in line
      with predictions, Studies 3 and 4 showed that executive functioning facilitates
      forgiveness only in the case of relatively severe (as compared with mild)
      offenses. Furthermore, Study 4 provided evidence for a psychological mechanism
      underlying the relation between executive functioning and forgiveness by
      demonstrating the mediating role of rumination about the offense. Implications of
      these findings for the literature on forgiveness and the role of executive
      functioning in interpersonal relationships more generally are discussed.

PMID- 20053038
TI  - Why are narcissists so charming at first sight? Decoding the narcissism
      popularity link at zero acquaintance.
AB  - On the basis of a realistic behavioral approach, the authors showed that
      narcissists are popular at zero acquaintance and aimed to explain why this is the
      case. In Study 1, a group of psychology freshmen (N = 73) judged each other on
      the basis of brief self-introductions using a large round-robin design (2,628
      dyads). Three main findings were revealed: First, narcissism leads to popularity
      at first sight. Second, the aspects of narcissism that are most maladaptive in
      the long run (exploitativeness/entitlement) proved to be most attractive at zero
      acquaintance. Third, an examination of observable verbal and nonverbal behaviors
      as well as aspects of physical appearance provided an explanation for why
      narcissists are more popular at first sight. Results were confirmed using
      judgments of uninvolved perceivers under 3 different conditions for which the
      amount of available information was varied systematically: (a) full information
      (video and sound, Study 2), (b) nonverbal information only (video only, Study 3),
      or (c) physical information only (still photograph of clothing, Study 4). These
      findings have important implications for understanding the inter- and
      intrapersonal dynamics of narcissism.

PMID- 20053039
TI  - The relative relativity of material and experiential purchases.
AB  - When it comes to spending disposable income, experiential purchases tend to make
      people happier than material purchases (Van Boven & Gilovich, 2003). But why are
      experiences more satisfying? We propose that the evaluation of experiences tends
      to be less comparative than that of material possessions, such that potentially
      invidious comparisons have less impact on satisfaction with experiences than with
      material possessions. Support for this contention was obtained in 8 studies. We
      found that participants were less satisfied with their material purchases because
      they were more likely to ruminate about unchosen options (Study 1); that
      participants tended to maximize when selecting material goods and satisfice when
      selecting experiences (Study 2); that participants examined unchosen material
      purchases more than unchosen experiential purchases (Study 3); and that, relative
      to experiences, participants' satisfaction with their material possessions was
      undermined more by comparisons to other available options (Studies 4 and 5A), to
      the same option at a different price (Studies 5B and 6), and to the purchases of
      other individuals (Study 5C). Our results suggest that experiential purchase
      decisions are easier to make and more conducive to well-being.

PMID- 20053040
TI  - Only three factors of personality description are fully replicable across
      languages: a comparison of 14 trait taxonomies.
AB  - We tested the hypothesis that only 3 factors of personality description are
      replicable across many different languages if they are independently derived by a
      psycholexical approach. Our test was based on 14 trait taxonomies from 12
      different languages. Factors were compared at each level of factor extraction
      with solutions with 1 to 6 factors. The 294 factors in the comparisons were
      identified using sets of markers of the 6-factor model by correlating the marker
      scales with the factors. The factor structures were pairwise compared in each
      case on the basis of the common variables that define the 2 sets of factors.
      Congruence coefficients were calculated between the varimax rotated structures
      after Procrustes rotation, where each structure in turn served as a target to
      which all other structures were rotated. On the basis of average congruence
      coefficients of all 91 comparisons, we conclude that factor solutions with 3
      factors on average are replicable across languages; solutions with more factors
      are not.

PMID- 20053041
TI  - What is coded into memory in the absence of outcome feedback?
AB  - Although people often have to learn from environments with scarce and highly
      selective outcome feedback, the question of how nonfeedback trials are
      represented in memory and affect later performance has received little attention
      in models of learning and decision making. In this article, the authors use the
      generalized context model (Nosofsky, 1986) as a vehicle to test contrasting
      hypotheses about the coding of nonfeedback trials. Data across 3 experiments with
      selective decision-contingent and selective outcome-contingent feedback provide
      support for the hypothesis of constructivist coding (Elwin, Juslin, Olsson, &
      Enkvist, 2007), according to which the outcomes on nonfeedback trials are coded
      with the most likely outcome, as inferred by the individual. The relation to
      sampling-based approaches to judgment, and the adaptive significance of
      constructivist coding, are discussed. (PsycINFO Database Record (c) 2009 APA, all
      rights reserved).

PMID- 20053042
TI  - The interaction of concreteness and phonological similarity in verbal working
      memory.
AB  - Although phonological representations have been a primary focus of verbal working
      memory research, lexical-semantic manipulations also influence performance. In
      the present study, the authors investigated whether a classic phenomenon in
      verbal working memory, the phonological similarity effect (PSE), is modulated by
      a lexical-semantic variable, word concreteness. Phonological overlap and
      concreteness were factorially manipulated in each of four experiments across
      which presentation modality (Experiments 1 and 2: visual presentation;
      Experiments 3 and 4: auditory presentation) and concurrent articulation (present
      in Experiments 2 and 4) were manipulated. In addition to main effects of each
      variable, results show a Phonological Overlap x Concreteness interaction whereby
      the magnitude of the PSE is greater for concrete word lists relative to abstract
      word lists. This effect is driven by superior item memory for nonoverlapping,
      concrete lists and is robust to the modality of presentation and concurrent
      articulation. These results demonstrate that in verbal working memory tasks,
      there are multiple routes to the phonological form of a word and that maintenance
      and retrieval occur over more than just a phonological level. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 20053043
TI  - Thinking about the weather: How display salience and knowledge affect performance
      in a graphic inference task.
AB  - Three experiments examined how bottom-up and top-down processes interact when
      people view and make inferences from complex visual displays (weather maps).
      Bottom-up effects of display design were investigated by manipulating the
      relative visual salience of task-relevant and task-irrelevant information across
      different maps. Top-down effects of domain knowledge were investigated by
      examining performance and eye fixations before and after participants learned
      relevant meteorological principles. Map design and knowledge interacted such that
      salience had no effect on performance before participants learned the
      meteorological principles; however, after learning, participants were more
      accurate if they viewed maps that made task-relevant information more visually
      salient. Effects of display design on task performance were somewhat dissociated
      from effects of display design on eye fixations. The results support a model in
      which eye fixations are directed primarily by top-down factors (task and domain
      knowledge). They suggest that good display design facilitates performance not
      just by guiding where viewers look in a complex display but also by facilitating
      processing of the visual features that represent task-relevant information at a
      given display location. (PsycINFO Database Record (c) 2009 APA, all rights
      reserved).

PMID- 20053044
TI  - Amount of postcue encoding predicts amount of directed forgetting.
AB  - In list-method directed forgetting, participants are cued to intentionally forget
      a previously studied list (List 1) before encoding a subsequently presented list
      (List 2). Compared with remember-cued participants, forget-cued participants
      typically show impaired recall of List 1 and improved recall of List 2, referred
      to as List 1 forgetting and List 2 enhancement. In 3 experiments, we examined how
      amount of postcue encoding influences directed forgetting. Two results emerged
      dissociating List 1 forgetting from List 2 enhancement. First, an increase in
      amount of postcue encoding led to an increase in List 1 forgetting but did not
      affect List 2 enhancement. Second, the forget cue influenced all List 1 items but
      affected only early List 2 items. A 2-mechanism account of directed forgetting is
      suggested, according to which List 1 forgetting reflects reduced accessibility of
      List 1 items, and List 2 enhancement arises from a reset of encoding processes.
      (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053046
TI  - Learning from feedback: Spacing and the delay-retention effect.
AB  - Most modern research on the effects of feedback during learning has assumed that
      feedback is an error correction mechanism. Recent studies of feedback-timing
      effects have suggested that feedback might also strengthen initially correct
      responses. In an experiment involving cued recall of trivia facts, we directly
      tested several theories of feedback-timing effects and also examined the effects
      of restudy and retest trials following immediate and delayed feedback. Results
      were not consistent with theories assuming that the only function of feedback is
      to correct initial errors but instead supported a theoretical account assuming
      that delaying feedback strengthens initially correct responses due to the spacing
      of encoding opportunities: Delaying feedback increased the probability of correct
      response perseveration on the final retention test but had minimal effects on
      error correction or error perseveration probabilities. In a 2nd experiment, the
      effects of varying the lags between study, test, and feedback trials during
      learning provided further support for the spacing hypothesis. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 20053045
TI  - The role of memory activation in creating false memories of encoding context.
AB  - Using 3 experiments, I examined false memory for encoding context by presenting
      Deese-Roediger-McDermott themes (Deese, 1959; Roediger & McDermott, 1995) in
      usual-looking fonts and by testing related, but unstudied, lure items in a font
      that was shown during encoding. In 2 of the experiments, testing lure items in
      the font used to study their associated themes increased false recognition
      relative to testing lure items in a font that was used to study a different
      lure's theme. Further, studying a larger number of associates exacerbated the
      influence of testing lure items in a font used to study their associated themes.
      Finally, testing lures in a font that was encoded many times, but was not used to
      present the lures' studied associates, increased lure errors more than testing
      lures in a font that was encoded relatively fewer times. These results favor the
      explanation of false recognition offered by global-matching models of recognition
      memory over the explanations of activation-monitoring theory and fuzzy-trace
      theory. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053047
TI  - Which words are activated during bilingual word production?
AB  - Whether words are or are not activated within the lexicon of the nonused language
      is an important question for accounts of bilingual word production. Prior studies
      have not led to conclusive results, either because alternative accounts could be
      proposed for their findings or because activation could have been artificially
      induced by the experimental paradigms. Moreover, previous data only involved
      target translations, and nothing is known about the activation of nontarget words
      in the nonused language. The picture-picture interference paradigm was used here,
      since it allowed the activation of nontarget words to be determined without
      showing stimuli that could artificially activate the nonused language. Proficient
      Spanish-Catalan speakers were presented with pairs of partially overlapping
      colored pictures and were instructed to name the green picture and ignore the red
      picture. In Experiment 1, distractor pictures with cognate names interfered more
      than distractor pictures with noncognate names. In Experiment 2, facilitation was
      observed when the names of the distractor pictures in the nonused language were
      phonologically related to the names of the target pictures. Overall, these
      results indicate that nontarget words are activated in the nonused language, at
      least in the case of proficient bilingual speakers. These results help
      researchers to constrain theories of bilingual lexical access. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 20053048
TI  - The effect of the temporal structure of spoken words on paired-associate
      learning.
AB  - In a series of experiments, participants learned to associate black-and-white
      shapes with nonsense spoken labels (e.g., "joop"). When tested on their
      recognition memory, participants falsely recognized as correct a shape paired
      with a label that began with the same sounds as the shape's original label (onset
      overlapping lure; e.g., joob) more often than a shape paired with a label that
      overlapped with the original label at offset (offset-overlapping lure; e.g.,
      choop). Furthermore, the false-alarm rate was modulated by the phonetic distance
      between the sounds that distinguished the original label and the lures. Greater
      false-alarm rates to onset-overlapping labels were not predicted by explicit
      similarity ratings or by consonant identification and were not dependent upon
      label familiarity. The asymmetry at erroneously recognizing onset- versus offset
      overlapping lures remained unchanged as the presentation of the shape at test was
      delayed in time, suggesting that response anticipation based on the first sounds
      of the spoken label did not contribute much to the false recognition of onset
      overlapping lures. Thus, learning 2 words whose names differ in their last sounds
      appears to pose greater difficulty than learning 2 words whose names differ in
      their first sounds because, we argue, people are biased to give more importance
      to the early sounds of a name than to its last sounds when learning a novel label
      referent association. (PsycINFO Database Record (c) 2009 APA, all rights
      reserved).

PMID- 20053049
TI  - One-reason decision making unveiled: a measurement model of the recognition
      heuristic.
AB  - The fast-and-frugal recognition heuristic (RH) theory provides a precise process
      description of comparative judgments. It claims that, in suitable domains,
      judgments between pairs of objects are based on recognition alone, whereas
      further knowledge is ignored. However, due to the confound between recognition
      and further knowledge, previous research lacked an unbiased measure of RH use.
      Also, model comparisons have not been based on goodness-of-fit and model
      complexity as criteria. To overcome both limitations we introduce and test a
      multinomial processing tree model showing that it fits empirical data and
      provides an unbiased measure of RH use. Analyses of 8 data sets reveal that the
      RH alone cannot account for the data, not even when it is implemented in a
      probabilistic way. That is, information integration beyond recognition plays a
      vital role and cannot merely account for empirical data better due to model
      flexibility. Also, we present several validations of the central model parameter
      and provide demonstrations of how the model can be applied to study the less-is
      more effect as well as determinants of (and individual differences in) RH use.
      (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053050
TI  - Pure mediated priming: a retrospective semantic matching model.
AB  - Mediated priming refers to the activation of a target (e.g., stripes) by a prime
      (e.g., lion) that is related indirectly via a connecting mediator (e.g., tiger).
      In previous mediated priming studies (e.g., McNamara & Altarriba, 1988), the
      mediator was associatively related to the prime. In contrast, pure mediated
      priming (e.g., spoon --> can) lacks a strong association between prime and
      mediator (e.g., spoon --> soup) and between mediator and target (e.g., soup -->
      can). This study establishes the existence of pure mediated priming and assesses
      which semantic priming model (spreading activation, compound-cue, or semantic
      matching) accounts for the results. Pure mediated priming occurred in 3
      experiments across double and standard lexical decision tasks. However, such
      priming did not occur in a continuous lexical decision task, which precludes
      strategic processing. Overall, results indicate that a modified retrospective
      semantic matching model provides the best theoretical explanation of pure
      mediated priming. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053051
TI  - Using maintenance rehearsal to explore recognition memory.
AB  - We examined associative and item recognition using the maintenance rehearsal
      paradigm. Our intent was to control for mnemonic strategies; to produce a low,
      graded level of learning; and to provide evidence of the role of attention in
      long-term memory. An advantage for low-frequency words emerged in both
      associative and item recognition at very low levels of learning. This early
      emergence casts doubt on explanations based on the traditional concept of
      recollection. A comparison of false alarms supports a role for item information
      or the joint use of cues but not familiarity in producing associative false
      alarms. We may also have found a way to measure the amount of attention being
      paid to a to-be-learned item or pair, independently of memory performance on the
      attended item. This result may be an important step in determining whether
      coherent theories about the role of attention in long- and short-term memory can
      be created. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053052
TI  - Syntactic constraints in the retrieval of homophone orthography.
AB  - In this experiment, syntactic constraints on the retrieval of orthography were
      investigated using homophones embedded in sentence contexts. Participants typed
      auditorily presented sentences that included a contextually appropriate homophone
      that either shared part of speech with its homophone competitor (i.e., was
      syntactically unambiguous) or had a different part of speech (was syntactically
      ambiguous). Each homophone was preceded by an unrelated word or a prime; primes
      were orthographically related to the competitor and shared or differed from the
      competitor's part of speech. For syntactically unambiguous homophones, more
      errors occurred overall, and priming increased errors independent of the prime's
      part of speech. For syntactically ambiguous homophones, priming occurred only
      following primes that shared part of speech with the competitor. These results
      demonstrate that written homophone errors can occur during lemma retrieval or
      during orthographic encoding, with the particular stage depending on the
      syntactic ambiguity of the homophone to be produced. (PsycINFO Database Record
      (c) 2009 APA, all rights reserved).

PMID- 20053053
TI  - The components of working memory updating: an experimental decomposition and
      individual differences.
AB  - Working memory updating (WMU) has been identified as a cognitive function of
      prime importance for everyday tasks and has also been found to be a significant
      predictor of higher mental abilities. Yet, little is known about the constituent
      processes of WMU. We suggest that operations required in a typical WMU task can
      be decomposed into 3 major component processes: retrieval, transformation, and
      substitution. We report a large-scale experiment that instantiated all possible
      combinations of those 3 component processes. Results show that the 3 components
      make independent contributions to updating performance. We additionally present
      structural equation models that link WMU task performance and working memory
      capacity (WMC) measures. These feature the methodological advancement of
      estimating interindividual covariation and experimental effects on mean updating
      measures simultaneously. The modeling results imply that WMC is a strong
      predictor of WMU skills in general, although some component processes-in
      particular, substitution skills-were independent of WMC. Hence, the reported
      predictive power of WMU measures may rely largely on common WM functions also
      measured in typical WMC tasks, although substitution skills may make an
      independent contribution to predicting higher mental abilities. (PsycINFO
      Database Record (c) 2009 APA, all rights reserved).

PMID- 20053054
TI  - Control of cost in prospective memory: evidence for spontaneous retrieval
      processes.
AB  - To examine the processes that support prospective remembering, previous research
      has often examined whether the presence of a prospective memory task slows
      overall responding on an ongoing task. Although slowed task performance suggests
      that monitoring is present, this method does not clearly establish whether
      monitoring is functionally related to prospective memory performance. According
      to the multiprocess theory (McDaniel & Einstein, 2000), monitoring should be
      necessary to prospective memory performance with nonfocal cues but not with focal
      cues. To test this hypothesis, we varied monitoring by presenting items that were
      related (or unrelated) to the prospective memory task proximal to target events.
      Notably, whereas monitoring proximal to target events led to a large increase in
      nonfocal prospective memory performance, focal prospective remembering was high
      in the absence of monitoring, and monitoring in this condition provided no
      additional benefits. These results suggest that when monitoring is absent,
      spontaneous retrieval processes can support focal prospective remembering.
      (PsycINFO Database Record (c) 2009 APA, all rights reserved).

PMID- 20053055
TI  - Congruency effects between number magnitude and response force.
AB  - Numbers are thought to be represented in space along a mental left-right oriented
      number line. Number magnitude has also been associated with the size of grip
      aperture, which might suggest a connection between number magnitude and
      intensity. The present experiment aimed to confirm this possibility more directly
      by using force as a response parameter. Participants judged parity of a single
      digit by executing a weak or forceful key press. Response selection was faster
      when small digits required a weak response and large digits required a forceful
      response than when this mapping was reversed. These findings indicate an effect
      of number magnitude on the initiation of response intensity. There was no
      evidence for such an effect on response execution because the actually applied
      response force was not associated with number magnitude. These findings confirm a
      previously postulated link between different magnitude domains such as number
      magnitude and intensity as a basis for action. (PsycINFO Database Record (c) 2009
      APA, all rights reserved).

PMID- 20053056
TI  - Reading times and the detection of event shift processing.
AB  - When people read narratives, they often need to update their situation models as
      the described events change. Previous research has shown little to no increases
      in reading times for spatial shifts but consistent increases for temporal shifts.
      On this basis, researchers have suggested that spatial updating does not
      regularly occur, whereas temporal updating does. The current study looked more
      deeply into this reading time pattern for spatial updating. If the prior
      interpretation is correct, then the absence of a reading time increase reflects a
      failure to update the situation model. Two experiments evaluated this claim by
      assessing whether other indicators of updating, namely memory probes, converge on
      a similar interpretation as that derived from the reading time data. Our results
      showed that, in contrast to previous accounts, although there was no change in
      the pattern of reading times, spatial updating was occurring and was extensive.
      As a comparison, we also looked at temporal updating. Unlike spatial updating,
      the temporal shifts had an influence on reading time but did not have as
      extensive an influence on memory probe performance. (PsycINFO Database Record (c)
      2009 APA, all rights reserved).

PMID- 20053057
TI  - Does perceived race affect discrimination and recognition of ambiguous-race
      faces? A test of the sociocognitive hypothesis.
AB  - Discrimination and recognition are often poorer for other-race than own-race
      faces. These other-race effects (OREs) have traditionally been attributed to
      reduced perceptual expertise, resulting from more limited experience, with other
      race faces. However, recent findings suggest that sociocognitive factors, such as
      reduced motivation to individuate other-race faces, may also contribute. If the
      sociocognitive hypothesis is correct, then it should be possible to alter
      discrimination and memory performance for identical faces by altering their
      perceived race. We made identical ambiguous-race morphed faces look either Asian
      or Caucasian by presenting them in Caucasian or Asian face contexts,
      respectively. However, this perceived-race manipulation had no effect on either
      discrimination (Experiment 1) or memory (Experiment 2) for the ambiguous-race
      faces, despite the presence of the usual OREs in discrimination and recognition
      of unambiguous Asian and Caucasian faces in our participant population. These
      results provide no support for the sociocognitive hypothesis. (PsycINFO Database
      Record (c) 2009 APA, all rights reserved).

PMID- 20053058
TI  - Separating mnemonic process from participant and item effects in the assessment
      of ROC asymmetries.
AB  - One of the most influential findings in the study of recognition memory is that
      receiver operating characteristic (ROC) curves are asymmetric about the negative
      diagonal. This result has led to the rejection of the equal-variance signal
      detection model of recognition memory and has provided motivation for more
      complex models, such as the unequal-variance signal detection and dual-process
      models. Here, the authors test the possibility that previous demonstrations of
      ROC asymmetry do not reflect mnemonic process but rather reflect distortions due
      to averaging data over items. Application of a hierarchical unequal-variance
      signal detection model reveals that asymmetries are in fact a real phenomenon and
      do not reflect distortions from averaging data. (PsycINFO Database Record (c)
      2009 APA, all rights reserved).

PMID- 20053059
TI  - Tests enhance the transfer of learning.
AB  - Numerous learning studies have shown that if the period of time devoted to
      studying information (e.g., casa-house) includes at least 1 test (casa-?),
      performance on a final test is improved-a finding known as the testing effect. In
      most of these studies, however, the final test is identical to the initial test.
      If the final test requires a novel demonstration of learning (i.e., transfer),
      prior studies suggest that a greater degree of transfer reduces the size of the
      testing effect. The authors tested this conjecture. In 2 experiments, 4th- or 5th
      grade students learned to assign regions or cities to map locations and returned
      1 day later for 2 kinds of final tests. One final test required exactly the same
      task seen during the learning session, and the other final test consisted of
      novel, more challenging questions. In both experiments, testing effects were
      found for both kinds of final tests, and the testing effect was no smaller, and
      actually slightly larger, for the final test requiring transfer. (PsycINFO
      Database Record (c) 2009 APA, all rights reserved).

PMID- 20053060
TI  - The contributions of primary and secondary memory to working memory capacity: an
      individual differences analysis of immediate free recall.
AB  - The present study tested the dual-component model of working memory capacity
      (WMC) by examining estimates of primary memory and secondary memory from an
      immediate free recall task. Participants completed multiple measures of WMC and
      general intellectual ability as well as multiple trials of an immediate free
      recall task. It was demonstrated that there are 2 sources of variance (primary
      memory and secondary memory) in immediate free recall and that, further, these 2
      sources of variance accounted for independent variation in WMC. Together, these
      results are consistent with a dual-component model of WMC reflecting individual
      differences in maintenance in primary memory and in retrieval from secondary
      memory. Theoretical implications for working memory and dual-component models of
      free recall are discussed. (PsycINFO Database Record (c) 2009 APA, all rights
      reserved).

PMID- 20053061
TI  - Evidence of metacognitive control by humans and monkeys in a perceptual
      categorization task.
AB  - Metacognition research has focused on the degree to which nonhuman primates share
      humans' capacity to monitor their cognitive processes. Convincing evidence now
      exists that monkeys can engage in metacognitive monitoring. By contrast, few
      studies have explored metacognitive control in monkeys, and the available
      evidence of metacognitive control supports multiple explanations. The current
      study addresses this situation by exploring the capacity of human participants
      and rhesus monkeys (Macaca mulatta) to adjust their study behavior in a
      perceptual categorization task. The study found that humans and monkeys increased
      their study for high-difficulty categories, suggesting that both share the
      capacity to exert metacognitive control. (PsycINFO Database Record (c) 2009 APA,
      all rights reserved).

PMID- 20053063
TI  - Metacognitive control and the spacing effect.
AB  - This study investigates whether the use of a spacing strategy absolutely improves
      final performance, even when the learner had chosen, metacognitively, to mass.
      After making judgments of learning, adult and child participants chose to mass or
      space their study of word pairs. However, 1/3 of their choices were dishonored.
      That is, they were forced to mass after having chosen to space and forced to
      space after having chosen to mass. Results showed that the spacing effect
      obtained for both adults and children when choices were honored. However, using a
      spacing strategy when it was in disagreement with the participant's own choice,
      or forced, did not enhance performance for the adults (Experiment 1). And
      although performance was enhanced for the children (beyond massing strategies),
      it was not as good as when the spacing decisions were self-chosen (Experiment 2).
      The data suggest that although spacing is an effective strategy for learning, it
      is not universal, particularly when the strategy is not chosen by the learner. In
      short, metacognitive control is often crucial and should be honored. (PsycINFO
      Database Record (c) 2009 APA, all rights reserved).

PMID- 20053064
TI  - Averaging facial expression over time.
AB  - The visual system groups similar features, objects, and motion (e.g., Gestalt
      grouping). Recent work suggests that the computation underlying perceptual
      grouping may be one of summary statistical representation. Summary representation
      occurs for low-level features, such as size, motion, and position, and even for
      high level stimuli, including faces; for example, observers accurately perceive
      the average expression in a group of faces (J. Haberman & D. Whitney, 2007,
      2009). The purpose of the present experiments was to characterize the time-course
      of this facial integration mechanism. In a series of three experiments, we
      measured observers' abilities to recognize the average expression of a temporal
      sequence of distinct faces. Faces were presented in sets of 4, 12, or 20, at
      temporal frequencies ranging from 1.6 to 21.3 Hz. The results revealed that
      observers perceived the average expression in a temporal sequence of different
      faces as precisely as they perceived a single face presented repeatedly. The
      facial averaging was independent of temporal frequency or set size, but depended
      on the total duration of exposed faces, with a time constant of approximately 800
      ms. These experiments provide evidence that the visual system is sensitive to the
      ensemble characteristics of complex objects presented over time.

PMID- 20053065
TI  - The spatial tuning of adaptation-based time compression.
AB  - Temporal processing is traditionally dissociated from spatial vision. Recent
      evidence, however, has shown that adaptation to high temporal frequency (D. Burr,
      A.Tozzi, & M. C. Morrone, 2007; A. Johnston, D. H. Arnold, & S. Nishida, 2006; A.
      Johnston et al., 2008) induces spatially specific reductions in the apparent
      duration of subsecond intervals containing medium frequency drift or flicker.
      Here we examine the spatial tuning of these temporal adaptation effects. Our
      results show that duration compression is tightly tuned to the spatial location
      of the adaptor and can be induced by very narrow adaptors. We also demonstrate
      that the effects of adaptation on perceived duration are dissociable from those
      on apparent temporal frequency, which suggests early but separate influences of
      temporal frequency adaptation on time and speed perception.

PMID- 20053066
TI  - No capacity limit in attentional tracking: evidence for probabilistic inference
      under a resource constraint.
AB  - Human ability to simultaneously track multiple items declines with set size. This
      effect is commonly attributed to a fixed limit on the number of items that can be
      attended to, a notion that is formalized in limited-capacity and slot models.
      Instead, we propose that observers are constrained by stimulus uncertainty that
      increases with the number of items but use Bayesian inference to achieve optimal
      performance. We model five data sets from published deviation discrimination
      experiments that varied set size, number of deviations, and magnitude of
      deviation. A constrained Bayesian observer better explains each data set than do
      the traditional limited-capacity model, the recently proposed slots-plus
      averaging model, a fixed-uncertainty Bayesian model, a Bayesian model with
      capacity limit, and a simple averaging model. This indicates that the notion of
      limited capacity in attentional tracking needs to be revised. Moreover, it
      supports the idea that Bayesian optimality of human perception extends to high
      level perceptual computations.

PMID- 20053068
TI  - An object-color space.
AB  - Putting aside metaphorical meanings of the term, color space is understood as a
      vector space, where lights having the same color (i.e., subjectively
      indistinguishable) are represented as a point. The CIE 1931 color space,
      empirically based on trichromatic color measurements, is a classical example. Its
      derivatives, such as CIELAB and sRGB, have been successfully used in many
      applications (e.g., in color management). However, having been designed for
      presenting the color of self-luminous objects, these spaces are less suitable for
      presenting color of reflecting objects. Specifically, they can be used to
      represent color of objects only for a fixed illumination. Here I put forward a
      color space to represent the color of objects independently of illumination. It
      is based on an ideal color atlas comprising the reflectance spectra taking two
      values: k or 1 - k (0 < or = k < or = 1), with two transitions (at wavelengths
      lambda(1) and lambda(2)) across the spectrum. This color atlas is complete; that
      is, every reflecting object is metameric to some element of the atlas. When
      illumination alters, the classes of metameric reflectance spectra are reshuffled
      but in each class there is exactly one element of the atlas. Hence, the atlas can
      uniquely represent the metameric classes irrespective of illumination. Each
      element of the atlas (thus, object color) is specified by three numbers: (i)
      lambda = (lambda(1) + lambda(2))/2, which correlates well with hue of object
      color (as dominant wavelength correlates with hue of light color); (ii) delta
      =/lambda(1) - lambda/, which correlates with whiteness/blackness; and (iii) alpha
      =/1 - 2k/, which correlates with chroma of object color (as colorimetric purity
      correlates with saturation of light color). Using a geographical coordinate
      system, each element of the atlas (thus, each object color) is geometrically
      represented as a radius vector so that its length equals alpha, the latitude and
      longitude being proportional to delta and lambda, respectively.

PMID- 20053067
TI  - Accommodative and vergence responses to conflicting blur and disparity stimuli
      during development.
AB  - Accommodative and vergence responses of the typically developing visual system
      are generated using a combination of cues, including retinal blur and disparity.
      The developmental importance of blur and disparity cues in generating these motor
      responses was assessed by placing the two cues in conflict with each other. Cue
      conflicts were induced by placing either -2 D lenses or 2 MA base-out prisms
      before both eyes of 140 subjects (2.0 months to 40.8 years) while they watched a
      cartoon movie binocularly at 80 cm. The frequency and amplitude of accommodation
      to lenses and vergence to prisms increased with age (both p < 0.001), with the
      vergence response (mean +/- 1 SEM = 1.38 +/- 0.05 MA) being slightly larger than
      the accommodative response (1.18 +/- 0.04 D) at all ages (p = 0.007). The
      amplitude of these responses decreased with an increase in conflict stimuli (1 to
      3 D or MA) (both p < 0.01). The coupled vergence response to -2 D lenses (0.31 +/
      0.06 MA) and coupled accommodative response to 2 MA base-out prisms (0.21 +/-
      0.02 D) were significantly smaller than (both p < 0.001) and poorly correlated
      with the open-loop vergence (r = 0.12; p = 0.44) and open-loop accommodation (r =
      -0.08; p = 0.69), respectively. The typically developing visual system
      compensates for transiently induced conflicts between blur and disparity stimuli,
      without exhibiting a strong preference for either cue. The accuracy of this
      compensation decreases with an increase in amplitude of cue-conflict.

PMID- 20053069
TI  - Downhill slopes look shallower from the edge.
AB  - A dramatic failure of orientation constancy is documented in the perception of
      downhill slopes. Contrary to naive expectation, steep downhill slopes look
      shallower from the edge than they do from back from the edge. Three experiments
      document and quantify this failure of constancy for real and virtual surfaces
      using a variety of dependent measures. Two additional studies document
      overestimation of both non-visually perceived head pitch and perceived gaze
      declination. A model of orientation constancy failure is fit to the data that
      combine exaggerations in perceived gaze declination with exaggerated scaling of
      perceived optical slant. These findings support a functional scale-expansion
      model of error in slope perception.

PMID- 20053070
TI  - Smooth pursuit performance during target blanking does not influence the
      triggering of predictive saccades.
AB  - Visually guided catch-up saccades during the pursuit of a moving target are
      highly influenced by smooth pursuit performance. For example, the decision to
      execute a saccade and its amplitude is driven by the difference in velocity
      between the eye and the target. In previous studies, we have demonstrated that
      the predictive saccades that occur during the blanking of the moving target
      compensate for the variability of the smooth pursuit response. Therefore, we
      wondered whether the predictive smooth pursuit response during target blanking
      influenced the occurrence of predictive saccades, which is the case for visually
      guided catch-up saccades. To answer this question, we asked subjects to track
      visually a target moving along a circular path. From time to time, the target was
      unexpectedly blanked for some randomized durations and disappeared from the
      screen. Surprisingly, we did not find any differences in smooth pursuit
      performance between the blanks that did and those that did not contain predictive
      saccades. In addition, during the blanks, the differences in smooth pursuit
      performance across the sessions or across the subjects did not correlate with the
      differences in the number of predictive saccades. Therefore, this study
      demonstrates that smooth pursuit performance does not influence the occurrence of
      predictive saccades. We interpret these results in light of the possible
      minimization of position error at target reappearance, which heavily depends on
      the saccadic amplitudes but not on their timing.

PMID- 20053071
TI  - The effects of target template specificity on visual search in real-world scenes:
      evidence from eye movements.
AB  - We can locate an object more quickly in a real-world scene when a specific target
      template is held in visual working memory, but it is not known exactly how a
      target template's specificity affects real-world search. In the present study, we
      compared word and picture cues in real-world scene search. Using an eye-tracker,
      we segmented search time into three behaviorally defined epochs: search
      initiation time, scanning time, and verification time. Results from three
      experiments indicated that target template specificity affects scanning and
      verification time. Within the scanning epoch, target template specificity
      affected the number of scene regions visited and the mean fixation duration.
      Changes to SOA did not affect this pattern of results. Similarly, the pattern of
      results did not change when participants were familiarized with target images
      prior to testing, suggesting that an immediately preceding picture provides a
      more useful search template than one stored in long-term memory. The results
      suggest that the specificity of the target cue affects both the activation map
      representing potential target locations and the process that matches a fixated
      object to an internal representation of the target.

PMID- 20053072
TI  - Visual search without attentional displacement.
AB  - The time needed to search for an object in a complex environment increases with
      the number of distracting stimuli, a phenomenon known as the "set-size effect."
      This observation has led to the view that, during visual search, several
      attentional shifts are performed, suggesting that visual information is processed
      serially. In an attempt to find direct evidence for such attentional shifts, we
      implemented several dual tasks combining a covert visual search (CVS) task or a
      cued target detection task with a character reporting task which allowed us to
      determine, a posteriori, the attentional allocation. We found that, in the cueing
      task, subjects preferentially reported characters displayed at different
      locations, demonstrating that the attention spotlight actually shifted in this
      condition. In contrast, in both feature and conjunction CVS, subjects
      predominantly reported several characters flashed at the same location, whatever
      the delay between their presentations, indicating that, despite a clear "set-size
      effect," attention remained static. These results demonstrate that CVS can be
      performed without shifting attention and that the "set-size effect" does not
      necessarily attest that visual information is processed serially. The present
      study therefore supports the hypothesis that parallel mechanisms are involved in
      visual information processing during visual search, in agreement with previous
      theoretical studies.

PMID- 20053073
TI  - Image statistics do not explain the perception of gloss and lightness.
AB  - A fundamental problem in image analysis is to understand the nature of the
      computations and mechanisms that provide information about the material
      properties of surfaces. Information about a surface's 3D shape, optics,
      illumination field, and atmospheric conditions are conflated in the image, which
      must somehow be disentangled to derive the properties of surfaces. It was
      recently suggested that the visual system exploits some simple image statistics
      histogram or sub-band skew-to infer the lightness and gloss of surfaces (I.
      Motoyoshi, S. Nishida, L. Sharan, & E. H. Adelson, 2007). Here, we show that the
      correlations Motoyoshi et al. (2007) observed between skew, lightness, and gloss
      only arose because of the limited space of surface geometries, reflectance
      properties, and illumination fields they evaluated. We argue that the lightness
      effects they reported were a statistical artifact of equating the means of images
      with skewed histograms, and that the perception of gloss requires an analysis of
      the consistency between the estimate of a surface's 3D shape and the positions
      and orientations of highlights on a surface. We argue that the derivation of
      surface and material properties requires a photo-geometric analysis, and that
      purely photometric statistics such as skew fail to capture any diagnostic
      information about surfaces because they are devoid of the structural information
      needed to distinguish different types of surface attributes.

PMID- 20053074
TI  - Motion-aftereffect-induced blindness.
AB  - Motion-induced blindness (MIB) describes the occasional disappearance of salient
      visual objects in the presence of moving features (Y. S. Bonneh, A. Cooperman, &
      D. Sagi, 2001). Here we test whether motion adaptation and the ensuing motion
      aftereffect (MAE) are sufficient to trigger disappearance of salient targets. In
      three experiments, observers adapted to either rotating or static stimuli.
      Immediately afterwards, a static test pattern was presented consisting of a mask
      with texture elements and three superimposed target dots in a triangular
      arrangement. Observers reported dot disappearance and reappearance. The results
      clearly show that illusory motion in a static test pattern, following motion
      adaptation, promotes the disappearance of target dots. Furthermore, disappearance
      is modulated by the depth relationship between test pattern and targets,
      increasing for targets placed stereoscopically behind the test pattern. We
      conclude that MIB is influenced by perceived relative motion between depth
      segregated features.

PMID- 20053075
TI  - Portraits made to measure: manipulating social judgments about individuals with a
      statistical face model.
AB  - The social judgments people make on the basis of the facial appearance of
      strangers strongly affect their behavior in different contexts. However, almost
      nothing is known about the physical information underlying these judgments. In
      this article, we present a new technology (a) to quantify the information in
      faces that is used for social judgments and (b) to manipulate the image of a
      human face in a way which is almost imperceptible but changes the personality
      traits ascribed to the depicted person. This method was developed in a high
      dimensional face space by identifying vectors that capture maximum variability in
      judgments of personality traits. Our method of manipulating the salience of these
      vectors in faces was successfully transferred to novel photographs from an
      independent database. We evaluated this method by showing pairs of face
      photographs which differed only in the salience of one of six personality traits.
      Subjects were asked to decide which face was more extreme with respect to the
      trait in question. Results show that the image manipulation produced the intended
      attribution effect. All response accuracies were significantly above chance
      level. This approach to understanding and manipulating how a person is socially
      perceived could be useful in psychological research and could also be applied in
      advertising or the film industries.

PMID- 20053076
TI  - The effect of crowding on orientation-selective adaptation in human early visual
      cortex.
AB  - Crowding is the identification difficulty for a target in the presence of nearby
      flankers. Based on psychophysical findings, many theories have been proposed to
      explain crowding at multiple levels. However, little is known about its neural
      mechanism. In this study, we combined psychophysical and fMRI adaptation
      techniques to search for the cortical locus of crowding. In the psychophysical
      experiment, when subjects' attention was controlled, we found that the threshold
      elevation aftereffect (TEAE) was not affected by crowding, regardless of the
      contrast level of adapting stimulus. In the fMRI experiment, the orientation
      selective fMRI adaptation in V1 was not affected by crowding either. However,
      downstream from V1, we found that crowding weakened the adaptation effect in V2
      and V3. Our results demonstrate that crowding occurs beyond V1 and provide one of
      the first pieces of direct evidence supporting the two-stage model of crowding
      (D. M. Levi, 2008).

PMID- 20053077
TI  - What is binocular vision for? A birds' eye view.
AB  - It is proposed that with the possible exception of owls, binocularity in birds
      does not have a higher order function that results in the perception of solidity
      and relative depth. Rather, binocularity is a consequence of the requirement of
      having a portion of the visual field that looks in the direction of travel;
      hence, each eye must have a contralateral projection that gives rise to
      binocularity. This contralateral projection is necessary to gain a symmetrically
      expanding optic flow-field about the bill. This specifies direction of travel and
      time to contact a target during feeding or when provisioning chicks. In birds
      that do not need such control of their bill, binocular field widths are very
      small, suggesting that binocular vision plays only a minor role in the control of
      locomotion. In the majority of birds, the function of binocularity would seem to
      lie in what each eye does independently rather than in what the two eyes might be
      able to do together. The wider binocular fields of owls may be the product of an
      interaction between enlarged eyes and enlarged outer ears, which may simply
      prevent more lateral placement of the eyes.

PMID- 20053078
TI  - Experience-dependent changes in the topography of visual crowding.
AB  - The present work examined discrimination accuracy for targets that were presented
      either alone in the visual field (clean displays) or embedded within a dense
      array of letter distractors (crowded displays). The strength of visual crowding
      varied strongly across the four quadrants of the visual field. Furthermore, this
      spatial bias in crowding was strongly influenced by the observers' prior
      experience with specific distractor stimuli. Observers who were monolingual
      readers of English experienced amplified crowding in the upper-left quadrant,
      while subjects with primary reading skills in Korean, Chinese, or Japanese tended
      towards worse target discrimination in the lower visual field. This interaction
      with language experience was eliminated when non-alphanumeric stimuli were
      employed as distractors, suggesting that prior reading experience induced a
      stimulus-specific change in the topography of visual crowding from English
      letters.

PMID- 20053079
TI  - Involuntary cueing effects on accuracy measures: Stimulus and task dependence.
AB  - Observers reported the orientation of a tilted grating that was presented
      together with a vertical distractor grating. In the main experiments, target
      contrast was low. There was location uncertainty because target location varied
      randomly and differences between target and distractor were small. In contrast to
      a previous report (T. Liu, F. Pestilli, & M. Carrasco, 2005), our results showed
      that non-informative peripheral cues do not improve perceptual performance at the
      cued location. However, informative peripheral or central cues improved
      perceptual performance. When we changed the task from an unspeeded perceptual
      task to a speeded reaction time task, the absence of involuntary cueing effects
      persisted when a distractor was presented. Without distractors, involuntary
      cueing effects re-emerged. When target contrast was increased, involuntary cueing
      effects re-emerged with a distractor but were smaller than without. We suggest
      that more difficult perceptual tasks reduce or abolish involuntary cueing
      effects.

PMID- 20053080
TI  - Orientation-tuned suppression in binocular rivalry reveals general and specific
      components of rivalry suppression.
AB  - During binocular rivalry (BR), conflicting monocular images are alternately
      suppressed from awareness. During suppression of an image, contrast sensitivity
      for probes is reduced by approximately 0.3-0.5 log units relative to when the
      image is in perceptual dominance. Previous studies on rivalry suppression have
      led to controversies concerning the nature and extent of suppression during BR.
      We tested for feature-specific suppression using orthogonal rivaling gratings and
      measuring contrast sensitivity to small grating probes at a range of orientations
      in a 2AFC orientation discrimination task. Results indicate that suppression is
      not uniform across orientations: suppression was much greater for orientations
      close to that of the suppressed grating. The higher suppression was specific to a
      narrow range around the suppressed rival grating, with a tuning similar to V1
      orientation bandwidths. A similar experiment tested for spatial frequency tuning
      and found that suppression was stronger for frequencies close to that of the
      suppressed grating. Interestingly, no tuned suppression was observed when a
      flicker-and-swap paradigm was used, suggesting that tuned suppression occurs only
      for lower-level, interocular rivalry. Together, the results suggest there are two
      components to rivalry suppression: a general feature-invariant component and an
      additional component specifically tuned to the rivaling features.

PMID- 20053081
TI  - Attentive and pre-attentive aspects of figural processing.
AB  - Here we use the steady-state visual evoked potential (SSVEP) to study attentive
      versus non-attentive processing of simple texture-defined shapes. By "tagging"
      the figure and background regions with different temporal frequencies, the method
      isolates response components associated with the figure region, the background
      region, and with non-linear spatio-temporal interactions between regions. Each of
      these response classes has a distinct scalp topography that is preserved under
      differing attentional task demands. In one task, attention was directed to
      discrimination of shape changes in the figure region. In the other task, a
      difficult letter discrimination was used to divert attentive processing resources
      away from the texture-defined form. Larger task-dependent effects were observed
      for figure responses and for the figure/background interaction than for the
      background responses. The figure region responses were delayed in occipital areas
      in the shape versus letter task conditions, while the region interactions were
      enhanced, especially in frontal areas. While a basic differentiation of figure
      from background processing occurred independent of task, attentive processing of
      elementary shapes recruited later occipital activity for figure processing and
      sustained non-linear figure/background interaction in frontal areas.
      Collectively, these results indicate that basic aspects of scene segmentation
      proceed pre-attentively, but that directed attention to the object shape engages
      a widely distributed network of brain areas including frontal and occipital
      regions.

PMID- 20053082
TI  - Tactile force perception depends on the visual speed of the collision object.
AB  - Previous research on the interaction between vision and touch has employed static
      visual and continuous tactile stimuli, and has shown that two kinds of multimodal
      interaction effect exist: the averaging effect and the contrast effect. The
      averaging effect has been used to explain several kinds of stimuli interaction
      while the contrast effect is associated only with the size-weight illusion (A.
      Charpentier, 1891). Here, we describe a novel visuotactile interaction using
      visual motion information that can be explained with the contrast effect. We show
      that the magnitude of tactile force perception (MTFP) from an impact on the palm
      is significantly modified by the visual motion information of a virtual collision
      event. Our collision simulator generates visual stimuli independently from the
      corresponding tactile stimuli. The results show that visual speed modified MTFP
      even though the actual contact force remained constant: higher visual pre- and
      post-collision speeds induced lower tactile force perception. Finally, we propose
      a quantitative model of MTFP in which MTFP is expressed as a function of the
      visual velocity difference, suggesting that the gain of the tactile perception in
      the human brain is altered via MTFP modulation.

PMID- 20053083
TI  - Relative contributions of 2D and 3D cues in a texture segmentation task,
      implications for the roles of striate and extrastriate cortex in attentional
      selection.
AB  - Experimental evidence has given strong support to the theory that the primary
      visual cortex (V1) realizes a bottom-up saliency map (A. R. Koene & L. Zhaoping,
      2007; Z. Li, 2002; L. Zhaoping, 2008a; L. Zhaoping & K. A. May, 2007). Unlike the
      conventional models of texture segmentation, this theory predicted that
      segmenting two textures in an image I(rel) comprising obliquely oriented bars
      would become much more difficult when a task-irrelevant texture I(ir) of
      spatially alternating horizontal and vertical bars is superposed on the original
      texture I(rel). The irrelevant texture I(ir) interferes with I(rel)'s ability to
      direct attention. This predicted interference was confirmed (L. Zhaoping & K. A.
      May, 2007) in the form of a prolonged task reaction time (RT). In this study, we
      investigate whether and how 3D depth perception, believed to be processed mostly
      beyond V1 and starting in V2 (J. S. Bakin, K. Nakayama, & C. D. Gilbert, 2000; B.
      G. Cumming & A. J. Parker, 2000; F. T. Qiu & R. von der Heydt, 2005; R. von der
      Heydt, H. Zhou, & H. S. Friedman, 2000), contribute additionally to direct
      attention. We measured the reduction of the interference or the RT when the
      position of the texture grid for I(ir) was offset horizontally from that for
      I(rel), forming an offset, 2D, stimulus. This reduction was compared with that
      when this positional offset was only present in the input image to one eye, or
      when it was in the opposite directions in the images for the two eyes, creating a
      3D stimulus with a depth separation between I(ir) and I(rel). The contribution by
      3D processes to attentional guidance would be manifested by any extra RT
      reduction associated with the 3D stimulus over the offset 2D stimulus. This 3D
      contribution was not present unless the task was so difficult that RT (by button
      press) based on 2D cues alone was longer than about 1 second. Our findings
      suggest that, without other top-down factors, V1 plays a dominant role in
      attentional guidance during an initial window of processing, while cortical areas
      beyond V1 play an increasing role in later processing. Subject-dependent
      variations in the manifestations of the 3D effects also suggest that this later,
      3D, contribution to attentional guidance can be easily influenced by top-down
      control.

PMID- 20053084
TI  - Size tuning and contextual modulation of backward contrast masking.
AB  - The strength of contrast masking depends not only on spatial but also on temporal
      parameters. In a previous study (T. P. Saarela & M. H. Herzog, 2008), we showed
      that the detection of a briefly presented Gabor patch is most strongly impaired
      when an iso-oriented grating mask immediately follows the Gabor and that this
      masking effect is relieved when a surround is added to the mask. Here, we studied
      the spatial characteristics of this backward masking effect. Gradually changing
      the size of the iso-oriented masking grating changes contrast detection
      thresholds in a non-monotonic way that can be explained in terms of contrast
      dependent spatial summation and inhibition. However, these spatial interactions
      seem only to take place when the mask is a uniform grating. When the mask is
      divided into a small center and a larger surround by changing the surround
      parameters or by adding a small gap, masking is as strong as with the small
      center mask only. We suggest that spatial interactions are weaker or even absent
      when the stimulus elements are perceptually segregated.

PMID- 20053085
TI  - The roles of mask luminance and perceptual grouping in visual backward masking.
AB  - Visual backward masking is a commonly used technique in vision research and
      psychology. There are two distinct types of masking. Either masking is strongest
      for a simultaneous presentation of the target and the mask (A-type masking) or
      masking is strongest when the mask trails the target (B-type masking). To account
      for the two types of masking, a variety of explanations have been put forward
      that often rely on low-level features such as the target-mask energy ratio.
      However, recent studies have demonstrated that the global spatial layout of the
      mask is an equally important factor. Here, we investigated both factors jointly.
      Our findings show that both factors strongly interact with each other and that
      neither one alone can explain the results. This finding indicates that choosing a
      mask should not be taken lightly when masking is used as a tool to investigate
      properties of perception or cognition.

PMID- 20053086
TI  - A new theory of structure-from-motion perception.
AB  - Humans can recover 3-D structure from the projected 2D motion field of a rotating
      object, a phenomenon called structure from motion (SFM). Current models of SFM
      perception are limited to the case in which objects rotate about a frontoparallel
      axis. However, as our recent psychophysical studies showed, frontoparallel axes
      of rotation are not representative of the general case. Here we present the first
      model to address the problem of SFM perception for the general case of rotations
      around an arbitrary axis. The SFM computation is cast as a two-stage process. The
      first stage computes the structure perpendicular to the axis of rotation. The
      second stage corrects for the slant of the axis of rotation. For cylinders, the
      computed object shape is invariant with respect to the observer's viewpoint (that
      is, perceived shape doesn't change with a change in the direction of the axis of
      rotation). The model uses template matching to estimate global parameters such as
      the angular speed of rotation, which are then used to compute the local depth
      structure. The model provides quantitative predictions that agree well with
      current psychophysical data for both frontoparallel and non-frontoparallel
      rotations.

PMID- 20053087
TI  - Mechanisms underlying perceptual learning of contrast detection in adults with
      anisometropic amblyopia.
AB  - What underlies contrast sensitivity improvements in adults with anisometropic
      amblyopia following perceptual learning in grating contrast detection? In this
      paper, we adopted the external noise approach (Z.-L. Lu & B. A. Dosher, 1998) to
      identify the mechanisms underlying perceptual learning in adults with
      anisometropic amblyopia. By measuring contrast thresholds in a range of external
      noise conditions at two performance levels (79.3% and 70.7%), we found that a
      mixture of internal additive noise reduction and external noise exclusion
      underlay training induced contrast sensitivity improvements in adults with
      anisometropic amblyopia. In comparison, normal adults exhibited only small amount
      of external noise exclusion under the same training conditions. The results
      suggest that neural plasticity may be more robust in amblyopia, lending further
      support of perceptual learning as a potential treatment for adult amblyopia.

PMID- 20053088
TI  - Everyone knows what is interesting: salient locations which should be fixated.
AB  - Most natural scenes are too complex to be perceived instantaneously in their
      entirety. Observers therefore have to select parts of them and process these
      parts sequentially. We study how this selection and prioritization process is
      performed by humans at two different levels. One is the overt attention mechanism
      of saccadic eye movements in a free-viewing paradigm. The second is a conscious
      decision process in which we asked observers which points in a scene they
      considered the most interesting. We find in a very large participant population
      (more than one thousand) that observers largely agree on which points they
      consider interesting. Their selections are also correlated with the eye movement
      pattern of different subjects. Both are correlated with predictions of a purely
      bottom-up saliency map model. Thus, bottom-up saliency influences cognitive
      processes as far removed from the sensory periphery as in the conscious choice of
      what an observer considers interesting.

PMID- 20053089
TI  - Different cue weights at the same place.
AB  - The visual system uses multiple cues to estimate properties of interest. Since
      the errors in the estimates from different cues for the same property are
      generally different, a weighted average of the cues provides a better overall
      estimate. The most precise estimate is found when each cue's weight is
      proportional to its reliability. We here show that the weights given to cues for
      surface slant can differ between two transparent surfaces that are at the same
      location at the same time. Thus the weights must be assigned separately for each
      structure, rather than for each location.

PMID- 20053090
TI  - Separate motion-detecting mechanisms for first- and second-order patterns
      revealed by rapid forms of visual motion priming and motion aftereffect.
AB  - Fast adaptation biases the perceived motion direction of a subsequently presented
      ambiguous test pattern (R. Kanai & F. A. Verstraten, 2005). Depending on both the
      duration of the adapting stimulus (ranging from tens to hundreds of milliseconds)
      and the duration of the adaptation-test blank interval, the perceived direction
      of an ambiguous test pattern can be biased towards the same or the opposite
      direction of the adaptation pattern, resulting in rapid forms of motion priming
      or motion aftereffect respectively. These findings were obtained employing
      drifting luminance gratings. Many studies have shown that first-order motion
      (luminance-defined) and second-order motion (contrast-defined) stimuli are
      processed by separate mechanisms. We assessed whether these effects also exist
      within the second-order motion domain. Results show that fast adaptation to
      second-order motion biases the perceived direction of a subsequently presented
      second-order ambiguous test pattern with similar time courses to that obtained
      for first-order motion. To assess whether a single mechanism could account for
      these results, we ran a cross-order adaptation condition. Results showed little
      or no transfer between the two motion cues and probes, suggesting a degree of
      separation between the neural substrates subserving fast adaptation of first- and
      second-order motion.

PMID- 20053092
TI  - Nonlinear characterization of a simple process in human vision.
AB  - Perceptual processes are often modeled as linear filters followed by a decisional
      rule. This simple model is central to the understanding of visual processing in
      humans. Its scope may be extended to capture a wider range of behaviors by the
      addition of nonlinear operators or kernels, but there is no evidence in human
      sensory processing that these operators are able to enhance the linear
      description. We focused on a simple process in human vision, the perception of
      brightness in a center-surround annular stimulus. We used psychophysical reverse
      correlation to fully characterize this process up to its second-order
      nonlinearity. The resulting characterization was then used to reconstruct/predict
      individual responses by the human observers, a process that was significantly
      enhanced by the addition of the nonlinear kernels. These results provide direct
      evidence that behavioral second-order kernels can be successfully derived using
      reverse correlation, and furthermore that they can be effectively exploited to
      simulate human vision. We show that the former result does not imply the latter
      by performing a second series of experiments involving orientation-defined
      textures, for which no measurable benefit was gained from the addition of second
      order kernels.

PMID- 20053091
TI  - Dissociable effects of attention and crowding on orientation averaging.
AB  - It has been proposed that visual crowding-the breakdown in recognition that
      occurs when objects are presented in cluttered scenes-reflects a limit imposed by
      visual attention. We examined this idea in the context of an orientation
      averaging task, having subjects judge the mean orientation of a set of oriented
      signal elements either in isolation, or "crowded" by nearby randomly oriented
      elements. In some conditions, subjects also had to perform an attentionally
      demanding secondary task. By measuring performance at different levels of signal
      orientation variability, we show that crowding increases subjects' local
      uncertainty (about the orientation of individual elements) but that diverting
      attention reduces their global efficiency (the effective number of elements they
      can average over). Furthermore, performance with the same stimulus-sequence,
      presented multiple times, reveals that crowding does not induce more stimulus
      independent variability (as would be predicted by some accounts based on
      attention). We conclude that crowding and attentional load have dissociable
      perceptual consequences for orientation averaging, suggesting distinct neural
      mechanisms for both. For the task we examined, attention can modulate the effects
      of crowding by changing the efficiency with which information is analyzed by the
      visual system but since crowding changes local uncertainty, not efficiency,
      crowding does not reflect an attentional limit.

PMID- 20053094
TI  - Orientation tuning of curvature adaptation reveals both curvature-polarity
      selective and non-selective mechanisms.
AB  - We have used a curvature after-effect, or CAE, to explore whether curvature
      detectors are tuned for the overall orientation of a curve. CAEs were measured
      for half-cycle cosine-shaped contours as a function of adaptor contour
      orientation for a fixed test contour orientation. CAEs (i) were greatest when the
      adaptor and test contours had the same orientation, (ii) decreased rapidly as the
      orientation of the adapting contours rotated away from the test, the data being
      well fit by a Gaussian function with a standard deviation of 16 degrees , (iii)
      increased again to a secondary peak when the adapting contours were rotated 180
      degrees relative to the test. Control experiments showed that the shape of the
      curvature-orientation tuning function could not be explained by local orientation
      adaptation, and that instead curvature encoding mechanisms are tuned for
      orientation. The secondary peak in the CAE at 180 degrees is argued to be
      inconsistent with curvature opponency and instead a result of the combination of
      polarity-selective and polarity-non-selective curvature mechanisms. The results
      are discussed in relation to recent psychophysical and physiological models of
      form processing and the possible significance of the findings with regard to
      symmetry processing.

PMID- 20053093
TI  - The initial torsional Ocular Following Response (tOFR) in humans: a response to
      the total motion energy in the stimulus?
AB  - We recorded the initial torsional Ocular Following Responses (tOFRs) elicited at
      short latency by visual images that occupied the frontal plane and rotated about
      the lines of sight. Using 1-D radial gratings, the local spatio-temporal
      characteristics of these tOFRs closely resembled those we previously reported for
      the hOFRs to horizontal motion with 1-D vertical gratings. When the 1-D radial
      grating was subdivided into a number of concentric annuli, each with the same
      radial thickness, tOFRs were less than predicted from the sum of the responses to
      the individual annuli: spatial normalization. However, the normalization was much
      weaker than that which we previously reported for the hOFRs. Further, when the
      number, thickness and contrast of these concentric annuli were varied
      systematically, the latency and magnitude of the tOFRs were well described by
      single monotonic functions when plotted against the product of the total area of
      the annuli and the square of their Michelson contrast ("A*C(2)"), consistent with
      the hypothesis that the onset and magnitude of the initial tOFR are determined by
      the total motion energy in the stimulus. When our previously published hOFR data
      were plotted against A*C(2), a single monotonic function sufficed to describe the
      latency but not the magnitude.

PMID- 20053095
TI  - The sliding window of audio-visual simultaneity.
AB  - Humans exist in an environment wherein many unrelated events occur in close
      spatial and temporal proximity. Audio-visual timing experiments, however, have
      often examined only isolated pairs of sensory events. We therefore decided to
      assess how audio-visual timing perception would be shaped by the presence of an
      additional audio or visual event. We found that the point of subjective synchrony
      for a sensory event can be shifted away from the presence of other temporally
      proximate events. These interactions made audio-visual pairs seem unrelated, or
      asynchronous, at timings at which they had seemed synchronous when presented in
      isolation. This shows that the interval across which humans are insensitive to
      audio-visual asynchrony is not fixed, but dynamic, shaped by interactions between
      multiple sensory events. Importantly, we establish that these interactions can
      enhance the sensitivity of timing judgments. These interactions could therefore
      help to segregate unrelated sensory events across time. Such effects are likely
      to be common in the cluttered environments in which humans exist.

PMID- 20053097
TI  - Categorical color constancy for simulated surfaces.
AB  - Color constancy is the ability to perceive constant surface colors under varying
      lighting conditions. Color constancy has traditionally been investigated with
      asymmetric matching, where stimuli are matched over two different contexts, or
      with achromatic settings, where a stimulus is made to appear gray. These methods
      deliver accurate information on the transformations of single points of color
      space under illuminant changes, but can be cumbersome and unintuitive for
      observers. Color naming is a fast and intuitive alternative to matching, allowing
      data collection from a large portion of color space. We asked observers to name
      the colors of 469 Munsell surfaces with known reflectance spectra simulated under
      five different illuminants. Observers were generally as consistent in naming the
      colors of surfaces under different illuminants as they were naming the colors of
      the same surfaces over time. The transformations in category boundaries caused by
      illuminant changes were generally small and could be explained well with simple
      linear models. Finally, an analysis of the pattern of naming consistency across
      color space revealed that largely the same hues were named consistently across
      illuminants and across observers even after correcting for category size effects.
      This indicates a possible relationship between perceptual color constancy and the
      ability to consistently communicate colors.

PMID- 20053096
TI  - Latency characteristics of the short-wavelength-sensitive cones and their
      associated pathways.
AB  - There are many distinct types of retinal ganglion and LGN cells that have
      opponent cone inputs and which may carry chromatic information. Of interest are
      the asymmetries in those LGN cells that carry S-cone signals: in S-ON cells, S+
      signals are opposed by (L + M) whereas, in many S-OFF cells, L+ signals are
      opposed by (S + M), giving -S + L - M (C. Tailby, S. G. Solomon, & P. Lennie,
      2008). However, the S-opponent pathway is traditionally modeled as +/-[S - (L +
      M)]. A phase lag of the S-cone signal has been inferred from psychophysical
      thresholds for discriminating combinations of simultaneous sinusoidal modulations
      along +/-[L - M] and +/-[S - (L + M)] directions (C. F. Stromeyer, R. T. Eskew,
      R. E. Kronauer, & L. Spillmann, 1991). We extend this experiment, measuring
      discrimination thresholds as a function of the phase delay between pairs of
      orthogonal component modulations. When one of the components isolates the tritan
      axis, there are phase delays at which discrimination is impossible; when neither
      component is aligned with the tritan axis, discrimination is possible at all
      delays. The data imply that the S-cone signal is delayed by approximately 12 ms
      relative to (L - M) responses. Given that post-receptoral mechanisms show diverse
      tuning around the tritan axis, we suggest that the delay arises before the S
      opponent channels are constructed, possibly in the S-cones themselves.

PMID- 20053098
TI  - Recalibration of multisensory simultaneity: cross-modal transfer coincides with a
      change in perceptual latency.
AB  - After exposure to asynchronous sound and light stimuli, perceived audio-visual
      synchrony changes to compensate for the asynchrony. Here we investigate to what
      extent this audio-visual recalibration effect transfers to visual-tactile and
      audio-tactile simultaneity perception in order to infer the mechanisms
      responsible for temporal recalibration. Results indicate that audio-visual
      recalibration of simultaneity can transfer to audio-tactile and visual-tactile
      stimuli depending on the way in which the multisensory stimuli are presented.
      With presentation of co-located multisensory stimuli, we found a change in the
      perceptual latency of the visual stimuli. Presenting auditory stimuli through
      headphones, on the other hand, induced a change in the perceptual latency of the
      auditory stimuli. We argue that the difference in transfer depends on the
      relative trust in the auditory and visual estimates. Interestingly, these
      findings were confirmed by showing that audio-visual recalibration influences
      simple reaction time to visual and auditory stimuli. Presenting co-located
      stimuli during asynchronous exposure induced a change in reaction time to visual
      stimuli, while with headphones the change in reaction time occurred for the
      auditory stimuli. These results indicate that the perceptual latency is altered
      with repeated exposure to asynchronous audio-visual stimuli in order to
      compensate (at least in part) for the presented asynchrony.

PMID- 20053099
TI  - Stereoscopic discrimination of the layout of ground surfaces.
AB  - Safe and effective locomotion depends critically on judgements of the surface
      properties of the ground to be traversed. Little is known about the role of
      binocular vision in surface perception at distances relevant to visually guided
      locomotion in humans. Programmable arrays of illuminated targets were used to
      present sparsely textured surfaces with real depth at distances of 4.5 and 9.0 m.
      Psychophysical measurements of discrimination thresholds demonstrated a clear
      superiority for stereoscopic over monocular judgments of relative and absolute
      surface slant. Judgements of surface roughness in particular demonstrated a
      substantial binocular advantage. Binocular vision is thus shown to directly
      contribute to judgements of the layout of terrain up to at least 4.5 m, and its
      smoothness to at least 9.0 m. Hence binocular vision could support moment-to
      moment wayfinding and path planning, especially when monocular cues are weak.

PMID- 20053100
TI  - Origin of the fast negative ERG component from isolated aspartate-treated mouse
      retina.
AB  - The leading edge of the a-wave of the ERG is generally believed to accurately
      reflect the changes in the circulating current through the cGMP-gated channels in
      the outer segment plasma membrane of rods and cones. The aspartate-isolated
      mammalian electroretinogram (ERG) to a rod-saturating flash contains a fast
      "nose"-like wave temporally overlapping with the a-wave. We characterize the
      nature of this nose, investigate the membrane current mechanisms involved in the
      nose mechanism, and propose a model that can explain the generation of the nose
      component in the rod inner segment. On the basis of pharmacological treatments
      and perfusate ion composition alterations we rule out the possible role of most
      of the known rod membrane current mechanisms that might participate in the
      generation of the ERG nose component and we propose that the nose is generated by
      the interplay of voltage-dependent K(x) and h channels together with the
      Na(+)/K(+) ATPase. Our results strengthen the view that the kinetics of the
      leading edge of the ERG photoresponses should correspond to that of the outer
      segment light-sensitive current.

PMID- 20053101
TI  - Faces and text attract gaze independent of the task: Experimental data and
      computer model.
AB  - Previous studies of eye gaze have shown that when looking at images containing
      human faces, observers tend to rapidly focus on the facial regions. But is this
      true of other high-level image features as well? We here investigate the extent
      to which natural scenes containing faces, text elements, and cell phones-as a
      suitable control-attract attention by tracking the eye movements of subjects in
      two types of tasks-free viewing and search. We observed that subjects in free
      viewing conditions look at faces and text 16.6 and 11.1 times more than similar
      regions normalized for size and position of the face and text. In terms of
      attracting gaze, text is almost as effective as faces. Furthermore, it is
      difficult to avoid looking at faces and text even when doing so imposes a cost.
      We also found that subjects took longer in making their initial saccade when they
      were told to avoid faces/text and their saccades landed on a non-face/non-text
      object. We refine a well-known bottom-up computer model of saliency-driven
      attention that includes conspicuity maps for color, orientation, and intensity by
      adding high-level semantic information (i.e., the location of faces or text) and
      demonstrate that this significantly improves the ability to predict eye fixations
      in natural images. Our enhanced model's predictions yield an area under the ROC
      curve over 84% for images that contain faces or text when compared against the
      actual fixation pattern of subjects. This suggests that the primate visual system
      allocates attention using such an enhanced saliency map.

PMID- 20053102
TI  - The role of vertical mirror symmetry in visual shape detection.
AB  - The goal of our study is a better understanding of the role of vertical mirror
      symmetry in perceptual grouping. With a simple psychophysical task and a set of
      controlled stimuli, we investigated whether vertical mirror symmetry acts as a
      cue in figure-ground segregation. We asked participants to indicate which of two
      sequentially presented Gabor arrays contained a visual shape. The shape was
      defined by a subset of Gabor elements positioned along the outline of an
      unfamiliar shape. By adding orientation noise to these Gabor elements, the shape
      percept became less salient. Across the different noise levels, symmetric shapes
      were easier to detect than asymmetric ones. This finding indicates that vertical
      mirror symmetry is indeed used as a cue in perceptual grouping.

PMID- 20053103
TI  - The fate of task-irrelevant visual motion: perceptual load versus feature-based
      attention.
AB  - We tested contrasting predictions derived from perceptual load theory and from
      recent feature-based selection accounts. Observers viewed moving, colored stimuli
      and performed low or high load tasks associated with one stimulus feature, either
      color or motion. The resultant motion aftereffect (MAE) was used to evaluate
      attentional allocation. We found that task-irrelevant visual features received
      less attention than co-localized task-relevant features of the same objects.
      Moreover, when color and motion features were co-localized yet perceived to
      belong to two distinct surfaces, feature-based selection was further increased at
      the expense of object-based co-selection. Load theory predicts that the MAE for
      task-irrelevant motion would be reduced with a higher load color task. However,
      this was not seen for co-localized features; perceptual load only modulated the
      MAE for task-irrelevant motion when this was spatially separated from the
      attended color location. Our results suggest that perceptual load effects are
      mediated by spatial selection and do not generalize to the feature domain.
      Feature-based selection operates to suppress processing of task-irrelevant, co
      localized features, irrespective of perceptual load.

PMID- 20053104
TI  - A summary-statistic representation in peripheral vision explains visual crowding.
AB  - Peripheral vision provides a less faithful representation of the visual input
      than foveal vision. Nonetheless, we can gain a lot of information about the world
      from our peripheral vision, for example in order to plan eye movements. The
      phenomenon of crowding shows that the reduction of information available in the
      periphery is not merely the result of reduced resolution. Crowding refers to
      visual phenomena in which identification of a target stimulus is significantly
      impaired by the presence of nearby stimuli, or flankers. What information is
      available in the periphery? We propose that the visual system locally represents
      peripheral stimuli by the joint statistics of responses of cells sensitive to
      different position, phase, orientation, and scale. This "textural" representation
      by summary statistics predicts the subjective "jumble" of features often
      associated with crowding. We show that the difficulty of performing an
      identification task within a single pooling region using this representation of
      the stimuli is correlated with peripheral identification performance under
      conditions of crowding. Furthermore, for a simple stimulus with no flankers, this
      representation can be adequate to specify the stimulus with some position
      invariance. This provides evidence that a unified neuronal mechanism may underlie
      peripheral vision, ordinary pattern recognition in central vision, and texture
      perception. A key component of our methodology involves creating visualizations
      of the information available in the summary statistics of a stimulus. We call
      these visualizations "mongrels" and show that they are highly useful in examining
      how the early visual system represents the visual input. Mongrels enable one to
      study the "equivalence classes" of our model, i.e., the sets of stimuli that map
      to the same representation according to the model.

PMID- 20053105
TI  - Monocular signals in human lateral geniculate nucleus reflect the Craik-Cornsweet
      O'Brien effect.
AB  - The human visual system has a remarkable ability to accurately estimate the
      relative brightness of adjacent objects despite large variations in illumination.
      However, the lightness of two identical equiluminant gray regions can appear
      quite different when a light-dark luminance transition falls between them. This
      illusory brightness "filling-in" phenomenon, the Craik-Cornsweet-O'Brien (CCOB)
      illusion, exposes fundamental assumptions made by the visual system in estimating
      lightness, but its neural basis remains unclear. While the responses of high
      level visual cortex can be correlated with perception of the CCOB, simple
      computational models suggest that the effect may originate from a much lower
      level, possibly subcortical. Here, we used high spatial resolution functional
      magnetic resonance imaging to show that the CCOB illusion is strongly correlated
      with signals recorded from the human lateral geniculate nucleus. Moreover,
      presenting the light and dark luminance transitions that induce the CCOB effect
      separately to each eye abolishes the illusion, suggesting that it depends on eye
      specific signals. Our observations suggest that the CCOB effect arises from
      signals in populations of monocular neurons very early in the human
      geniculostriate visual pathway.

PMID- 20053106
TI  - Static and space-time visual saliency detection by self-resemblance.
AB  - We present a novel unified framework for both static and space-time saliency
      detection. Our method is a bottom-up approach and computes so-called local
      regression kernels (i.e., local descriptors) from the given image (or a video),
      which measure the likeness of a pixel (or voxel) to its surroundings. Visual
      saliency is then computed using the said "self-resemblance" measure. The
      framework results in a saliency map where each pixel (or voxel) indicates the
      statistical likelihood of saliency of a feature matrix given its surrounding
      feature matrices. As a similarity measure, matrix cosine similarity (a
      generalization of cosine similarity) is employed. State of the art performance is
      demonstrated on commonly used human eye fixation data (static scenes (N. Bruce &
      J. Tsotsos, 2006) and dynamic scenes (L. Itti & P. Baldi, 2006)) and some
      psychological patterns.

PMID- 20053107
TI  - Why are you angry with me? Facial expressions of threat influence perception of
      gaze direction.
AB  - Gaze direction can influence the processing of facial expressions. Angry faces
      are judged more angry when displaying a direct gaze compared to an averted gaze.
      We investigated whether facial expressions have a reciprocal influence on the
      perception of gaze. Participants judged the gaze of angry, fearful and neutral
      faces across a range of gaze directions. Angry faces were perceived as looking at
      the observer over a wider range than were fearful or neutral faces, which did not
      significantly differ. This effect was eliminated when presenting inverted faces,
      suggesting these results cannot be accounted for by differences in visible eye
      information. Our findings suggest the existence of a reciprocal influence between
      gaze direction and angry expressions.

PMID- 20053108
TI  - Orientation bandwidths are invariant across spatiotemporal frequency after
      isotropic components are removed.
AB  - It is well established that mammalian visual cortex possesses a large proportion
      of orientation-selective neurons. Attempts to measure the bandwidth of these
      mechanisms psychophysically have yielded highly variable results ( approximately
      6 degrees -180 degrees ). Two stimulus factors have been proposed to account for
      this variability: spatial and temporal frequency; with several studies indicating
      broader bandwidths at low spatial and high temporal frequencies. We estimated
      orientation bandwidths using a classic overlay masking paradigm across a range of
      spatiotemporal frequencies (0.5, 2, and 8 c.p.d.; 1.6 and 12.5 Hz) with target
      and mask presented either monoptically or dichoptically. A standard three
      parameter Gaussian model (amplitude and width, mean fixed at 0 degrees ) confirms
      that bandwidths generally increase at low spatial and high temporal frequencies.
      When incorporating an additional orientation-untuned (isotropic) amplitude
      component, however, we find that not only are the amplitudes of isotropic and
      orientation-tuned components highly dependent upon stimulus spatiotemporal
      frequency, but orientation bandwidths are highly invariant ( approximately 30
      degrees half width half amplitude). These results suggest that previously
      reported spatiotemporally contingent bandwidth effects may have confounded
      bandwidth with isotropic (so-called cross-orientation) masking. Interestingly,
      the magnitudes of all monoptically derived parameter estimates were found to
      transfer dichoptically suggesting a cortical locus for both isotropic and
      orientation-tuned masking.

PMID- 20053109
TI  - Preservation of shape discrimination in aging.
AB  - The representation of objects becomes increasingly complex at higher levels of
      the human visual cortex. Shapes of intermediate complexity serve as a step in the
      representation of such intricate constructs. Healthy aging has adverse effects on
      cortical function, and we sought to determine the effects of age on the efficacy
      and speed of neuronal mechanisms underlying shape processing. Using deformed
      circular shapes, we probe object representation by varying the characteristics
      that define the shape and by assessing lateral interactions among shapes. Results
      indicate that performance declines with age for shapes defined by texture but not
      by luminance. However, there is no age-related slowing for the processing of
      shape, and probes of lateral interactions reveal spared function for complex
      shape combinations. Findings suggest that the effect of age on shapes defined by
      texture arises from lower stages of visual processing, and that the
      representation of shape combinations is spared because of its robust nature.

PMID- 20053110
TI  - Face gender and emotion expression: are angry women more like men?
AB  - Certain features of facial appearance perceptually resemble expressive cues
      related to facial displays of emotion. We hypothesized that because expressive
      markers of anger (such as lowered eyebrows) overlap with perceptual markers of
      male sex, perceivers would identify androgynous angry faces as more likely to be
      a man than a woman (Study 1) and would be slower to classify an angry woman as a
      woman than an angry man as a man (Study 2). Conversely, we hypothesized that
      because perceptual features of fear (raised eyebrows) and happiness (a rounded
      smiling face) overlap with female sex markers, perceivers would be more likely to
      identify an androgynous face showing these emotions as a woman than as a man
      (Study 1) and would be slower to identify happy and fearful men as men than happy
      and fearful women as women (Study 2). The results of the two studies showed that
      happiness and fear expressions bias sex discrimination toward the female, whereas
      anger expressions bias sex perception toward the male.

PMID- 20053111
TI  - Effect of accommodation on peripheral ocular aberrations.
AB  - Changes in peripheral aberrations, particularly higher order aberrations, as a
      function of accommodation have received little attention. Wavefront aberrations
      were measured for the right eyes of 9 young adult emmetropes at 38 field
      positions in the central 42 x 32 degrees of the visual field. Subjects
      accommodated monocularly to targets at vergences of either 0.3 or 4.0 D.
      Wavefront data for a 5-mm diameter pupil were analyzed either in terms of the
      vector components of refraction or Zernike coefficients and total RMS wavefront
      aberrations. Relative peripheral refractive error (RPRE) was myopic at both
      accommodation demands and showed only a slight, not statistically significant,
      hypermetropic shift in the vertical meridian with the higher accommodation
      demand. There was little change in the astigmatic components of refraction or the
      higher order Zernike coefficients, apart from fourth-order spherical aberration,
      which became more negative (by 0.10 microm) at all field locations. Although it
      has been suggested that nearwork and the state of peripheral refraction may play
      some role in myopia development, for most of our adult emmetropes any changes
      with accommodation in RPRE and aberration were small. Hence it seems unlikely
      that such changes can be of importance to late-onset myopization.

PMID- 20053112
TI  - Oculomotor responses and visuospatial perceptual judgments compete for common
      limited resources.
AB  - While there is evidence for multiple spatial and attentional maps in the brain it
      is not clear to what extent visuoperceptual and oculomotor tasks rely on common
      neural representations and attentional mechanisms. Using a dual-task interference
      paradigm we tested the hypothesis that eye movements and perceptual judgments
      made to simultaneously presented visuospatial information compete for shared
      limited resources. Observers undertook judgments of stimulus collinearity
      (perceptual extrapolation) using a pointer and Gabor patch and/or performed
      saccades to a peripheral dot target while their eye movements were recorded. In
      addition, observers performed a non-spatial control task (contrast
      discrimination), matched for task difficulty and stimulus structure, which on the
      basis of previous studies was expected to represent a lesser load on putative
      shared resources. Greater mutual interference was indeed found between the
      saccade and extrapolation task pair than between the saccade and contrast
      discrimination task pair. These data are consistent with visuoperceptual and
      oculomotor responses competing for common limited resources as well as spatial
      tasks incurring a relatively high attentional cost.

PMID- 20053113
TI  - A masking analysis of glass pattern perception.
AB  - A Glass pattern consists of randomly distributed dot pairs (dipoles) whose
      orientations are determined by a geometric transform. To understand how an
      observer perceives the global structure, we investigated how the threshold for
      detecting a concentric or a radial Glass pattern (target) can be affected by the
      presence of another Glass pattern (masker). The Glass patterns had either
      concentric, radial, vertical, plaid, or spiral global forms. We used a 2AFC
      paradigm in which a mask was presented in both intervals while a target was
      randomly presented in one interval and a random dot pattern in the other. The
      target dot density thresholds were measured at 75% accuracy. For all masker
      types, the target threshold was constant at low masker densities and then
      increased with masker density. For concentric targets, concentric and spiral
      maskers had the best masking effect. For radial targets, a low-curvature spiral
      mask produced the best masking. The target threshold versus masker density
      functions were fit with a divisive inhibition model, in which the response of a
      global mechanism is the excitation of a linear template to the input image raised
      by a power and divided by the sum of an inhibition input and a constant.

PMID- 20053114
TI  - Effect of distance upon horizontal and vertical look and stare OKN.
AB  - Previous reports suggest that distance influences horizontal stare OKN gains;
      however, the effect of distance on vertical OKN and look OKN is unknown.
      Horizontal and vertical look and stare OKN gains were recorded in 16 healthy
      volunteers (velocity 38.4 degrees /s) at three distances (0.3 m, 1 m, and 2.5 m)
      and two different stimulus sizes. Asymmetry of responses and correlation of gains
      in different directions were compared. Measurements at near were compared with
      and without glasses. Distance did not significantly affect horizontal look and
      stare OKN or vertical look OKN, however, downward stare OKN gains were reduced at
      greater distances (p = 0.002). Mean downward stare OKN gains recorded in each
      individual were strongly correlated to leftward and rightward gains but not
      upward gains. In contrast, upward OKN gains were not correlated to gains in
      leftward, rightward, or downward directions. Downward stare OKN responses are
      significantly sensitive to the effects of distance, whereas stare OKN in other
      directions and look OKN responses in all directions are not. Individual mean
      downward stare OKN gains are more closely related to horizontal responses rather
      than upward responses. This suggests that the downward OKN system is more
      functionally related to the horizontal system rather than the upward OKN system.

PMID- 20053115
TI  - Stereo transparency in ambiguous stereograms generated by overlapping two
      identical dot patterns.
AB  - In binocular vision, observers can perceive transparent surfaces by fusing a
      stereogram composed of two overlapping patterns with different disparities. When
      dot patterns of two surfaces are identical, the stereogram has potential matches
      leading to both transparency and non-transparency (or unitary surface)
      perceptions. However, these two matching candidates are exclusive if the
      uniqueness assumption holds. This stereogram can be regarded as a random-dot
      version of the double-nail illusion and a stereo version of the locally paired
      dot stimulus that was used to investigate the neural mechanism for motion
      transparency. Which surface is perceived in this ambiguous stereogram would
      reflect the property of the transparency detection mechanism in human stereopsis.
      Here we perform a parametric study to examine the perceptual property in this
      ambiguous stereogram. The result showed that the ability in transparency
      detection from this stereogram is determined by the contrast reversal ratio
      between overlapping patterns within small regions the width of which was about
      0.4 deg. The width was similar to the receptive field sizes of neurons in striate
      cortex. The result suggests that the contrast reversal between two identical
      patterns would modulate activities of binocular neurons, and this modification
      gives a crucial effect on the neural representation for overlapping disparities.

PMID- 20053116
TI  - Immediate transfer of synesthesia to a novel inducer.
AB  - In synesthesia, a certain stimulus (e.g. grapheme) is associated automatically
      and consistently with a stable perceptual-like experience (e.g. color). These
      associations are acquired in early childhood and remain robust throughout the
      lifetime. Synesthetic associations can transfer to novel inducers in adulthood as
      one learns a second language that uses another writing system. However, it is not
      known how long this transfer takes. We found that grapheme-color associations can
      transfer to novel graphemes after only a 10-minute writing exercise. Most
      subjects experienced synesthetic associations immediately after learning a new
      Glagolitic grapheme. Using a Stroop task, we provide objective evidence for the
      creation of novel associations between the newly learned graphemes and
      synesthetic colors. Also, these associations generalized to graphemes handwritten
      by another person. The fast learning process and the generalization suggest that
      synesthesia begins at the semantic level of representation with the activation of
      a certain concept (the inducer), which then, uniquely for the synesthetes,
      activates representations at the perceptual level (the concurrent). Thus, the
      results imply that synesthesia is a much more flexible and plastic phenomenon
      than has been believed until now.

PMID- 20053117
TI  - Growth and differentiation of the larval mosquito midgut.
AB  - Factors affecting larval growth and nutrition have consequences on adult
      fecundity. Since the mosquito larval midgut is the primary organ of digestion and
      nutrient absorption, factors that affect the growth and development of the midgut
      may have potential consequences on the reproductive potential of the adult. To
      gain a better understanding of mosquito midgut development the growth and
      metamorphic remodeling of the Aedes aegypti L. and Culex pipiens L. (Diptera:
      Culicidae) midguts were investigated. Cytological evidence was obtained
      suggesting that, in both the anterior and posterior Ae. aegypti larval midgut,
      diploid regenerative cells give rise to new endoreplicating cells that
      significantly contribute to the growth and metabolism of the midgut. This
      hypothesis was supported by BrdU incorporation studies showing that diploid
      cells, as well as large and small endoreplicating cells, synthesize DNA during
      the 2(nd), 3(rd) and 4(th) instars. Cytological studies of the Cx. pipiens larval
      midgut suggest that anterior midgut growth in this species is primarily by cell
      enlargement. To study metamorphic remodeling of the midgut, DNA synthesis in Ae.
      aegypti 4(th) instar midguts was followed by using 5-bromo-2-deoxyuridine (BrdU)
      incorporation. During the 24 hr period after the last larval-larval molt both
      endoreplicating and diploid cells incorporate BrdU. After the critical weight is
      achieved, endoreplicating cell BrdU incorporation gradually ceases while diploid
      cells continue to replicate. The period of maximum diploid cell incorporation
      correlated with the period of maximum ecdysone titer.

PMID- 20053118
TI  - Hygienic behavior, liquid-foraging, and trophallaxis in the leaf-cutting ants,
      Acromyrmex subterraneus and Acromyrmex octospinosus.
AB  - Neotropical leaf-cutting ants (tribe Attini) live in obligate symbiosis with
      fungus they culture for food. To protect themselves and their fungus garden from
      pathogens, they minimize the entry of microorganisms through mechanical and
      chemical means. In this study, focusing on the species Acromyrmex subterraneus
      and A. octospinosus, (Hymeoptera: Formicidae). Self- and allo-grooming behavior
      were quantified and it was found that A. octospinosus workers spend less time in
      self-grooming than A. subterraneus. In the experimental absence of fungus in A.
      subterraneus, the times spent in these two behaviors are not affected; however
      workers spend significantly more time immobile. Hygienic and trophallaxis
      behaviors were examined as well as the possibility that workers exchange food,
      and the grooming behavior of foraging and non-foraging workers were compared.
      Behavioral observations revealed that large workers spent more time grooming than
      small workers, and more than 62% of replete foragers passed collected liquid food
      via trophallaxis to a nestmate. However, trophallaxis was rarely observed between
      non-forager workers. These results suggest that trophallaxis permits the exchange
      of alimentary liquid between colony members, but it is not important for
      spreading the colony odor signature.

PMID- 20053119
TI  - Toxicity, tunneling and feeding behavior of the termite, Coptotermes vastator, in
      sand treated with oil of the physic nut, Jatropha curcas.
AB  - Oil of the physic nut, Jatropha curcas L. (Malpighiales: Euphorbiaceae), was
      evaluated in the laboratory for its barrier and repellent activity against the
      Philippine milk termite Coptotermes vastator Light (Isoptera: Rhinotermitidae).
      The study showed that J. curcas oil had anti-feeding effect, induced reduction in
      tunneling activity and increased mortality in C. vastator. Behavior of termites
      exposed to sand treated with J. curcas oil indicated that it is toxic or
      repellent to C. vastator. Toxicity and repellent thresholds, were higher than
      those reported for other naturally occurring compounds tested against the
      Formosan subterranean termite.

PMID- 20053120
TI  - Evaluation of the susceptibility of the pea aphid, Acyrthosiphon pisum, to a
      selection of novel biorational insecticides using an artificial diet.
AB  - An improved technique was developed to assay the toxicity of insecticides against
      aphids using an artificial diet. The susceptibility of the pea aphid
      Acyrthosiphon pisum (Harris) (Hemiptera: Aphidoidea) was determined for a
      selection of novel biorational insecticides, each representing a novel mode of
      action. Flonicamid, a novel systemic insecticide with selective activity as
      feeding blocker against sucking insects, showed high toxicity against first
      instar A. pisum nymphs with an LC(50) of 20.4 microg/ml after 24 h, and of 0.24
      microg/ml after 72 h. The toxicity was compared with another feeding blocker,
      pymetrozine, and the neonicotinoid, imidacloprid. In addition, four insect growth
      regulators were tested. The chitin synthesis inhibitor flufenoxuron, the juvenile
      hormone analogue pyriproxyfen, and the azadirachtin compound Neem Azal-T/S showed
      strong effects and reduced the aphid population by 50% after 3 days of treatment
      at a concentration of 7-9 microg/ml. The ecdysone agonist tested, halofenozide,
      was less potent. In conclusion, the improved aphid feeding apparatus can be
      useful as a miniature screening device for insecticides against different aphid
      pests. The present study demonstrated rapid and strong toxicity of flonicamid,
      and other biorational insecticides towards A. pisum.

PMID- 20053121
TI  - Longevity and developmental stability in the dung fly Sepsis cynipsea, as
      affected by the ectoparasitic mite, Pediculoides mesembrinae.
AB  - Fluctuating asymmetry (FA) is a widely employed measure of developmental
      stability. It has been found to increase with many stressors including parasite
      infection. Associations between parasites and FA may exist for several reasons in
      addition to parasites being the direct cause of increased FA. Developmentally
      stable individuals may have superior immune systems, and be less susceptible to
      parasite infection, and/or may be less exposed to parasites than developmentally
      unstable ones. Mites negatively impact host fitness in a number of insects, and
      if FA is a reflection of general genetic quality, as has been proposed,
      associations between mite number and FA are predicted. Potential relationships
      were investigated between an ectoparasitic mite, Pediculoides mesembrinae
      (Canestrini) (Phthiraptera: Menoponidae) and FA in the common dung fly Sepsis
      cynipsea (L.) (Diptera: Sepsidae). While it was found that mite infested flies
      died much faster than flies without mites, indicating that mites indeed stress
      their hosts, counter to expectations, no associations between mites and FA were
      found in any analyses. Additionally, FA in mite-infected flies generally did not
      differ from previously published FA data from uninfected S. cynipsea.
      Nevertheless, parasitized males tended to be somewhat less asymmetrical than non
      parasitized males, but based on our data, it does not appear that mite
      infestation is generally associated with developmental stability in S. cynipsea.

PMID- 20053122
TI  - Olfactory perception of oviposition-deterring fatty acids and their methyl esters
      by the Asian corn borer, Ostrinia furnacalis.
AB  - Olfactory perception of myristic, palmitic, stearic and oleic acids and their
      corresponding methyl esters by Asian corn borer moths, Ostrinia furnacalis
      (Guenee) (Lepidoptera: Crambidae) was investigated. It was found that mated
      females with both antennae amputated, in contrast to intact females and females
      with one antenna removed, could not discriminate between simultaneously provided
      control filter papers and filters treated with a blend of oviposition-deterring
      fatty acids. Oviposition by mated females exhibited a very marked periodicity,
      with all egg masses deposited during the scotophase and most egg masses laid
      before midnight. According to the peak and trough period of oviposition,
      electroantennogram (EAG) responses from both mated females and males to the four
      fatty acids and four methyl esters were tested within two two-hour periods from 3
      to 5 hours after the start of darkness and from 1 to 3 hours after light onset,
      respectively. Significant EAG responses above solvent and background were
      elicited by all test chemicals from females, and by most of the test compounds
      from males. EAG values of all test chemicals from mated females were not
      statistically different between the two test periods except for methyl myristate.
      Conversely, EAG responses from mated males to myristic acid, stearic acid and
      their methyl esters significantly differed between the two test periods.

PMID- 20053123
TI  - High temperature effects on water loss and survival examining the hardiness of
      female adults of the spider beetles, Mezium affine and Gibbium aequinoctiale.
AB  - A remarkable ability to tolerate temperatures as high as 52 degrees C for Mezium
      affine Boieldieu and 56 degrees C for Gibbium aequinoctiale Boieldieu
      (Coleoptera: Anobiidae) was discovered as part of a water balance study that was
      conducted to determine whether desiccation-resistance (xerophilic water balance
      classification) is linked to survival at high temperature. Characteristics of the
      heat shock response were an intermediate, reversible level of injury, appearing
      as though dead; greater recovery from heat shock by G. aequinoctiale (57%) than
      M. affine (30%) that supplemented higher temperature survival by G.
      aequinoctiale; and lack of protection generated by conditioning at sublethal
      temperature. Heatinduced mortality is attributed to an abrupt, accelerated water
      loss at 50 degrees C for M. affine and 54 degrees C for G. aequinoctiale, not to
      the species (M. affine) that loses water the slowest and has the lower activation
      energy, E(a) as a measure of cuticular boundary effectiveness. These temperatures
      where water loss increases sharply are not critical transition temperatures
      because Arrhenius analysis causes them to be erased (uninterrupted Boltzmann
      function) and E(a) fails to change when cuticular lipid from these beetles is
      removed. Our conclusion is that the temperature thresholds for survival and
      accelerated water loss closely match, and the key survival element in hot and dry
      environments contributing to wide distribution of G. aequinoctiale and M. affine
      derives from rising temperature prompting entry into quiescence and a resistance
      in cuticular lipid fluidity.

PMID- 20053124
TI  - Genetic differentiation between resistance phenotypes in the phytophagous flea
      beetle, Phyllotreta nemorum.
AB  - The flea beetle Phyllotreta nemorum L. (Coleoptera: Chrysomelidae) is genetically
      polymorphic for resistance against the defences of one of its host plants,
      Barbarea vulgaris R.Br. (Brassicales: Brassicaceae). Whereas resistant flea
      beetles are able to use B. vulgaris as well as other cruciferous plants as food,
      non-resistant beetles cannot survive on B. vulgaris. This limitation to host
      plant use of non-resistant beetles could potentially lead to asymmetric gene flow
      and some degree of genetic isolation between the different resistance-genotypes.
      Therefore, we studied the extent of genetic differentiation at neutral allozyme
      loci between samples of flea beetles that were collected at different locations
      and first tested for resistance phenotype. Since earlier work has shown a weak,
      but significant, effect of geographical distance between the samples on their
      genetic differentiation, in the present study variation at the neutral allozyme
      loci in P. nemorum was partitioned between geographical distance and resistance
      phenotype. Both sources independently contributed statistically significantly to
      population differentiation. Thus, there appears to be a limitation to genetic
      exchange between the resistant and non-resistant flea beetles when corrections
      are made for their geographic differentiation. This is consistent with the
      presence of some degree of host race formation in this flea beetle.

PMID- 20053125
TI  - Digestive proteolytic activity in the Sunn pest, Eurygaster integriceps.
AB  - The Sunn pest, Eurygaster integriceps Puton (Heteroptera: Scutelleridae), is one
      of the most important pests of wheat and causes considerable damage to this
      valuable crop annually. Digestive proteinase activity of adult insects was
      investigated using general and specific substrates and inhibitors. Proteolytic
      activity was low when the common conventional substrates, azoalbumin, azocasein
      and hemoglobin were used to assay salivary glands and midguts. Using the
      fluorescent casein substrate (BODIPY FL casein), total proteolytic activity was
      measured at different pH. Maximum proteolytic activity was detected at pH 7
      (100%) and 8(65%) which suggested the presence of serine proteinases in the
      salivary glands. There was no detectable proteolytic activity in midgut extracts.
      The inhibitors; PMSF (inhibitor of serine proteinases) and TPCK (a specific
      chymotrypsin inhibitor) showed greater than 50% inhibitory effect on total
      proteolytic activity, however, TLCK (specific trypsin inhibitor) and E
      64(specific cysteine proteinase inhibitor) did not inhibit total proteolytic
      activity. Using fluorescent specific substrates for serine and cysteine
      proteinases (Z-Arg-AMC, Z-Arg-Arg-AMC, Z-Arg-Phe-AMC and Suc-Ala-Ala-Pro-Phe-AMZ)
      revealed the presence of tryptic and chymotryptic activity in the salivary gland
      extract. Zymogram analysis under non-reducing SDS-PAGE conditions and using the
      substrate APNE showed at least 8 tryptic and chymotryptic activity bands in
      salivary gland extracts. A single high molecular weight band with tryptic
      activity (165 kDa) was detected using the substrate BApNA in a zymogram analysis
      using native-PAGE. Kinetic studies showed a k(m) value of 0.6 mM for this enzyme
      against the substrate BApNA .The inhibitor TLCK decreased activity of the trypsin
      like enzyme up to 73% and almost completely eliminated the only band related to
      this proteinase in the zymogram. Soybean Kunitz type trypsin inhibitor showed no
      effect on proteolytic activity of the trypsin-like serine proteinase. In general,
      the results revealed the presence of chymotrypsin- and trypsin-like serine
      proteinases in the salivary gland of E. integriceps, and it seems that the major
      total proteolytic activity is due to chymotrypsin proteinases.

PMID- 20053126
TI  - Functional and morphological maturation of implanted neonatal cardiomyocytes as a
      comparator for cell therapy.
AB  - Knowledge of the rate of development of immature cardiomyocytes after
      implantation into a host heart is important for studies using cell therapy. To
      assess this functionally, we have implanted rat neonatal cardiomyocytes (NCMs) in
      normal and infarcted rat heart and re-isolated them for functional assessment.
      Maturation of implanted bone marrow stromal cells (BMSCs) was compared under
      similar conditions. NCMs from green fluorescent protein (GFP) transgenic rats
      were implanted into adult normal or infarcted rat hearts and re-isolated after 1,
      2, or 4 weeks by standard enzymatic digestion. BMSCs labeled with DiI and iron
      oxide were implanted into rats with myocardial infarction and cells re-isolated
      1, 2, 5, 6, and 16 weeks later. GFP-labeled myocytes approaching the adult
      morphology were detected 2 weeks after implantation of NCMs, but were
      significantly shorter than adult host myocytes and had reduced contractility. By
      4 weeks after implantation, re-isolated GFP-labeled myocytes were close to the
      adult phenotype in contractile characteristics, although still significantly
      shorter. Infarction of the host did not alter the rate of maturation of implanted
      cells. After implantation of BMSCs, small numbers of functional DiI-labeled
      myocytes were re-isolated from 4/11 animals but were more mature than expected
      from the NCM studies. This adds evidence that BMSC-derived cardiomyocytes were
      not a result of transdifferentiation. The maturation rate of implanted NCMs
      represents a benchmark against which to evaluate the likely rate of formation of
      fully functional cardiomyocytes from implanted cells.

PMID- 20053127
TI  - Inhibition of lipolysis by adiposomes containing glycosylphosphatidylinositol
      anchored Gce1 protein in rat adipocytes.
AB  - Small membrane vesicles released from large adipocytes and harbouring the
      glycosylphosphatidylinositol-anchored (GPI-) AMP-degrading protein CD73 have
      previously been demonstrated to stimulate the signal-induced esterification of
      free fatty acids into neutral lipids suggesting a role of these so-called
      adiposomes (ADIP) in the paracrine regulation of lipid metabolism in the adipose
      tissue. Here the involvement of another constituent GPI-protein of ADIP, the cAMP
      degrading protein Gce1 in the signal-induced inhibition of lipolysis was
      investigated in primary rat adipocytes. Incubation of small, and to a lower
      degree, large adipocytes with ADIP inhibited lipolysis and increased its
      sensitivity toward inhibition by H(2)O(2), the anti-diabetic drug glimepiride and
      palmitate. This was accompanied by the transfer of Gce1 from the ADIP to
      detergent-insoluble glycolipid-enriched plasma membrane microdomains (DIGs) and
      its subsequent translocation to cytoplasmic lipid droplets (LD) of the acceptor
      adipocytes. The translocation from DIGs to LD rather than the transfer from ADIP
      to DIGs of Gce1 was stimulated by H(2)O(2) > glimepiride > palmitate. Both
      transfer and translocation led to salt- and carbonate-resistant association of
      Gce1 with DIGs and LD, respectively, and relied on the structural integrity of
      the DIGs and GPI anchor of Gce1. In conclusion, the trafficking of GPI-proteins
      from ADIP of donor adipocytes via DIGs to LD of acceptor adipocytes mediates
      paracrine regulation of lipolysis within adipose tissue.

PMID- 20053128
TI  - HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome
      in chronic spinal cord injury.
AB  - Chronic spinal cord injury (SCI) is characterized by tissue loss and a stable
      functional deficit. While several experimental therapies have proven to be partly
      successful for the treatment of acute SCI, treatment of chronic SCI is still
      challenging. We studied whether we can bridge a chronic spinal cord lesion by
      implantation of our newly developed hydrogel based on 2-hydroxypropyl
      methacrylamide, either alone or seeded with mesenchymal stem cells (MSCs), and
      whether this treatment leads to functional improvement. A balloon-induced
      compression lesion was performed in adult 2-month-old male Wistar rats. Five
      weeks after injury, HPMA-RGD hydrogels [N-(2-hydroxypropyl)-methacrylamide with
      attached amino acid sequences--Arg-Gly-Asp] were implanted into the lesion,
      either with or without seeded MSCs. Animals with chronic SCI served as controls.
      The animals were behaviorally tested using the Basso-Beattie-Breshnahan (BBB)
      (motor) and plantar (sensory) tests once a week for 6 months. Behavioral analysis
      showed a statistically significant improvement in rats with combined treatment,
      hydrogel and MSCs, compared with the control group (P < 0.05). Although a
      tendency toward improvement was found in rats treated with hydrogel only, this
      was not significant. Subsequently, the animals were sacrificed 6 months after
      SCI, and the spinal cord lesions evaluated histologically. The combined therapy
      (hydrogel with MSCs) prevented tissue atrophy (P < 0.05), and the hydrogels were
      infiltrated with axons myelinated with Schwann cells. Blood vessels and
      astrocytes also grew inside the implant. MSCs were present in the hydrogels even
      5 months after implantation. We conclude that 5 weeks after injury, HPMA-RGD
      hydrogels seeded with MSCs can successfully bridge a spinal cord cavity and
      provide a scaffold for tissue regeneration. This treatment leads to functional
      improvement even in chronic SCI.

PMID- 20053129
TI  - Molecular abnormalities in pediatric barrett esophagus: can we test for potential
      of neoplastic progression?
AB  - Barrett esophagus (BE) is a preneoplastic condition that predisposes to
      esophageal adenocarcinoma and is a consequence of prolonged gastroesophageal
      reflux disease. The condition is mainly seen in adults and is thought to be a
      complex disease in which individual genetic predisposition interacts with
      environmental stimuli. The aim of our study was to investigate whether genetic
      biomarkers of potential disease progression are the same in the rare situation of
      pediatric BE, as described in adults. We performed fluorescence in situ
      hybridization with probes from Abbott Vysis Corporation on 4-micron sections
      taken from 48 paraffin-embedded sequential biopsies of 10 cases of BE. The 4
      probe sets were specific for HER2 at 17q12/17 centromere/4 centromere, p16 at
      9p21/9 centromere, TP53 at 17p13/17 centromere/6 centromere, and CCND1 at
      11q13/11 centromere. The probe sets were validated on 10 cases of adult Barrett
      adenocarcinoma. Of the 10 cases, 6 biopsies in 5 cases were informative. Two had
      gain of HER2 detected in 1 biopsy each (1 also had gain of chromosome 17) and 4
      separate cases showed p16 deletion in 1 biopsy of each (1 also had gain of
      chromosome 9). The genetic markers informative in 50% of our cases were also
      identified in adult patients with Barrett adenocarcinoma. The importance of this
      study is that even at the pediatric level, BE can show genetic changes associated
      with neoplastic progression.

PMID- 20053130
TI  - Young adult chondrocytes proliferate rapidly and produce a cartilaginous tissue
      at the gel-media interface in agarose cultures.
AB  - Primary chondrocytes cultured in agarose can escape the gel, accumulate at the
      interface between agarose and the culture medium, and form an outgrowing tissue.
      These outgrowths can appear as voluminous cartilage-like nodules that have never
      been previously investigated. In the present study, bovine articular chondrocytes
      from three age groups (fetal, young adult, aged) were seeded and cultured in
      agarose to test the hypothesis that hyaline-like cartilage outgrowths develop at
      the interface by appositional growth, in an age-dependant manner. Macroscopic
      appearance, cell content, cell division, cytoskeletal morphology, and
      extracellular matrix (ECM) composition were analyzed. Fetal chondrocytes produced
      a fibrous interfacial tissue while aged chondrocytes produced ECM-poor cell
      clusters. In contrast young adult chondrocytes produced large cartilaginous
      outgrowths, rich in proteoglycan and collagen II, where cells in the central
      region displayed a chondrocyte morphology. Cell proliferation was confined to the
      peripheral edge of these outgrowths, where elongated cell morphology, cell-cell
      contacts, and cell extensions toward the culture medium were seen. Thus these
      voluminous cartilaginous outgrowths formed in an appositional growth process and
      only for donor chondrocytes from young adult animals. This system offers an
      interesting ability to proliferate chondrocytes in a manner that results in a
      chondrocyte morphology and a cartilaginous ECM in central regions of the
      outgrowing tissue. It also provides an in vitro model system to study
      neocartilage appositional growth.

PMID- 20053131
TI  - Osteogenic differentiation capacity of porcine dental follicle progenitor cells.
AB  - This study examined the effect of extracellular matrix (ECM) on the osteogenic
      differentiation capacity and osteogenesis of dental follicle cells. Single cell
      derived porcine dental follicle cells (DFC-I) obtained at the early stage of
      crown formation in tooth were subcultured and characterized using periodontal
      ligament cells (PDLC) and bone marrow-derived mesenchymal stem cells (BMSC) as
      comparison cell populations. The effect of ECM constituents including collagen
      type I, fibronectin, laminin, and collagen type IV on the differentiation of DFC
      1 into osteogenic-lineage cells was evaluated in vitro. In addition, the DFC-1,
      PDLC, and BMSC populations were compared for osteogenic capacity in vitro by
      Alizarin red staining and in vivo by transplantation. DFC-I showed different
      features from PDLC and BMSC. Different components of ECM had different effects on
      the differentiation of DFC-1 into osteogenic-lineage cells in vitro. Alkaline
      phosphatase activity and matrix mineralization as early- and late-stage markers
      of osteogenesis, respectively, supported the differentiation of DFC-1 into
      osteogenic-related cells in vitro. All three cell types showed equivalent
      osteogenic capacity in vivo at 4 weeks postoperatively. There were no
      statistically significant differences among the cell populations with respect to
      capacity for bone formation. These results suggest a potential application for
      dental follicle cells in bone-tissue engineering.

PMID- 20053132
TI  - Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and
      interluekin-8 genes in dermal fibroblasts by copper.
AB  - Copper is essential to wound healing as well as a widespread environmental
      pollutant, with skin aging potential. Wound healing and skin aging are
      facilitated by matrixmetalloproteinases (MMP), which remodel the extracellular
      matrix, and interleukin-8 (IL-8), linked with copper. This research investigated
      the mechanism to copper's role in wound healing or skin aging by regulation of
      MMP-1 and IL-8 genes. It examined the dose-responsive effects of copper on MMP-1,
      -2, and -9 activities; MMP-1 and IL-8 gene regulation at protein, mRNA, and
      promoter levels; tissue inhibitor of matrixmetalloproteinases-1 (TIMP-1)
      expression; and cell proliferation. Copper stimulated cell proliferation and the
      expression of MMP-1 and IL-8 genes at the protein, mRNA, and promoter levels,
      indicating transcriptional regulation, without significantly altering TIMP-1. The
      research suggests that copper facilitates wound healing as well as skin aging via
      the induction of MMP-1 expression, with limiting MMP effect at the higher
      concentrations through enhanced IL-8 expression, which favors extracellular
      matrix deposition.

PMID- 20053135
TI  - Lack of demonstrable memory T cell responses in humans who have spontaneously
      recovered from leptospirosis in the Peruvian Amazon.
AB  - BACKGROUND. We tested the hypothesis that patients who have recovered from
      leptospirosis have peripheral blood memory T cells that are specific for
      Leptospira or Leptospira protein antigens. METHODS. Peripheral blood mononuclear
      cells (PBMCs) were obtained from patients who had recovered from leptospirosis,
      as well as from control individuals. PBMCs were assessed for in vitro
      proliferation, phenotyping, and cytokine production after stimulation with
      different strains of Leptospira, recombinant LipL32, or overlapping synthetic
      peptides of different outer membrane proteins. RESULTS. PBMCs from both control
      subjects and patients produced significant proliferative responses to all
      Leptospira strains. Proliferation from control PBMCs was significantly greater
      than responses produced by patient PBMCs. Select strains of Leptospira expanded
      both T cell receptor (TCR) alphabeta and TCRgammadelta T cells in both control
      subject and patient PBMCs. Patient and control subject PBMCs produced equivalent
      levels of tumor necrosis factor alpha and interferon gamma, but patient PBMCs
      produced significantly less interleukin 10 than did control subject PBMCs after
      stimulation by different strains of Leptospira. PBMCs from patients failed to
      respond to recombinant LipL32 or to any of the Leptospira peptides. CONCLUSION.
      Leptospira induced significant proliferative responses, TCRgammadelta T cell
      expansion, and cytokine production in both control subject and patient PBMCs.
      Patient PBMCs failed to recognize Leptospira protein antigens. Leptospirosis does
      not seem to generate memory T cells that can be activated by in vitro
      stimulation.

PMID- 20053133
TI  - RANKL inhibition improves bone properties in a mouse model of osteogenesis
      imperfecta.
AB  - Recently, a new class of agents targeting the receptor activator of nuclear
      factor-kappaB ligand (RANKL) pathway has been developed for the treatment of
      osteoporosis and other bone diseases. In the current study, inhibition of the
      RANKL pathway was evaluated to assess effects on "bone quality" and fracture
      incidence in an animal model of osteogenesis imperfect (OI), the oim/oim mouse.
      Juvenile oim/oim ( approximately 6 weeks old) and wildtype (+/+) mice were
      treated with either a RANKL inhibitor (RANK-Fc) or saline. After treatment, bone
      density increased significantly in the femurs of both genotypes. Femoral length
      decreased with RANK-Fc in +/+ mice. Geometric measurements at mid-diaphysis in
      the oim/oim groups showed increases in the ML periosteal and endosteal diameters
      and AP cortical thickness in the treated groups. Within +/+ groups, ML cortical
      thickness and ML femoral periosteal diameter were significantly increased with
      RANK-Fc. Biomechanical testing revealed increased stiffness in oim/oim and +/+
      mice. Total strain was increased with treatment in the +/+ mice. Histologically,
      RANKL inhibition resulted in retained growth plate cartilage in both genotypes.
      The average number of fractures sustained by RANK-Fc-treated oim/oim mice was not
      significantly decreased compared to saline treated oim/oim mice. This preclinical
      study demonstrated that RANKL inhibition at the current dose improved density and
      some geometric and biomechanical properties of oim/oim bone, but it did not
      decrease fracture incidence. Further studies that address commencement of therapy
      at earlier time points are needed to determine whether this mode of therapy will
      be clinically useful in OI.

PMID- 20053136
TI  - Transgenic mice enriched in omega-3 fatty acids are more susceptible to pulmonary
      tuberculosis: impaired resistance to tuberculosis in fat-1 mice.
AB  - BACKGROUND. Besides their health benefits, dietary omega-3 fatty acids (n-3
      PUFAs) can impair host resistance to intracellular pathogens. Previously, we and
      others have showed that n-3 PUFA-treated macrophages poorly control Mycobacterium
      tuberculosis infection in vitro. METHODS. Wild-type and fat-1 transgenic mice
      were infected with virulent H37Rv M. tuberculosis via the aerosol route. We
      evaluated bacteriological and histopathological changes in lungs, as well as
      differences in activation and antimycobacterial capacity in primary macrophages
      ex vivo. RESULTS. fat-1 mice were more susceptible to tuberculosis, as
      demonstrated by higher bacterial loads and less robust inflammatory responses in
      lungs. Macrophages obtained from fat-1 mice were more readily infected with M.
      tuberculosis in vitro, compared with wild-type macrophages. This impaired
      bacterial control in cells from fat-1 mice correlated with reduced
      proinflammatory cytokine secretion, impaired oxidative metabolism, and diminished
      M. tuberculosis-lysotracker colocalization within phagosomes. CONCLUSIONS. We
      showed that endogenous production of n-3 PUFAs in fat-1 mice increases their
      susceptibility to tuberculosis, which could be explained in part by diminished
      activation and antimycobacterial responses in cells from fat-1 mice. These data
      suggest that n-3 PUFA-supplemented diets might have a detrimental effect on
      immunity to M. tuberculosis and raise concerns regarding the safety of omega-3
      dietary supplementation in humans.

PMID- 20053139
TI  - Aromatase inhibitors alone or in sequence with tamoxifen - clinical evaluation of
      the BIG 1-98 trial.

PMID- 20053137
TI  - Attribution of hepatitis C virus seroconversion risk in young injection drug
      users in 5 US cities.
AB  - BACKGROUND. In studies of hepatitis C virus (HCV) seroconversion in injection
      drug users (IDUs), some have questioned whether underreporting of syringe
      sharing, a stigmatized behavior, has led to misattribution of HCV risk to other
      injection-related behaviors. METHODS. IDUs aged 15-30 years who were seronegative
      for human immunodeficiency virus and HCV antibodies were recruited into a
      prospective study in 5 US cities. Behavioral data were collected via computer
      assisted self-interviewing to reduce socially desirable reporting. Hazard ratios
      (HRs) were estimated to assess associations between behavior and HCV
      seroconversion. Because the shared use of cookers, cottons, and rinse water was
      highly correlated, a summary variable was created to represent drug preparation
      equipment sharing. RESULTS. Among 483 IDUs who injected during the period covered
      by the follow-up assessments, the incidence of HCV infection was 17.2 cases per
      100 person years; no HIV seroconversions occurred. Adjusting for confounders, the
      shared use of drug preparation equipment was significantly associated with HCV
      seroconversion (adjusted HR, 2.66; 95% confidence interval, 1.03-23.92), but
      syringe sharing was not (adjusted HR, 0.91). We estimated that 37% of HCV
      seroconversions in IDUs were due to the sharing of drug preparation equipment.
      CONCLUSIONS. Associations between sharing drug preparation equipment and HCV
      seroconversion are not attributable to underascertainment of syringe sharing.
      Avoiding HCV infection will require substantial reductions in exposure to all
      sources of contaminated blood.

PMID- 20053138
TI  - Adeno-associated vector (type 8)-mediated expression of soluble Flt-1 efficiently
      inhibits neovascularization in a murine choroidal neovascularization model.
AB  - To assess the feasibility of a gene therapeutic approach to treating choroidal
      neovascularization (CNV), we generated a recombinant adeno-associated viral (AAV)
      vector (type 8) encoding soluble Flt-1 (AAV-sflt-1), and determined its ability
      to inhibit angiogenesis. When we treated human umbilical vein endothelial cells
      (HUVECs) with the supernatant of cells transduced with AAV-sflt-1 or AAV-EGFP
      (control), we found that tube formation was significantly inhibited by the former
      but not the latter (area: 25,121 +/- 557 vs. 68,628 +/- 1357 pixels [p < 0.01];
      length: 4811 +/- 246 vs. 10,894 +/- 297 pixels [p < 0.01]). CNV was induced in
      C57BL/6 mice by making four separate choroidal burns around the optic nerve in
      each eye, using a diode laser. Thereafter, 2 microl (5 x 10(11) vector
      genomes/ml) of AAV-sflt-1 (n = 11) or control AAV-LacZ (n = 12) was injected into
      the subretinal space, and 2 weeks later the eyes were removed for flatmount
      analysis of CNV surface area. Notably, subretinal delivery of AAV-sflt-1
      significantly diminished CNV at the laser lesions, as compared with AAV-LacZ (555
      +/- 304 vs. 1470 +/- 1000 microm(2); p = 0.007). These results suggest that there
      was diffusion of the secreted sFlt-1 across the retina and that long-term
      suppression of CNV is possible through the use of stable rAAV-mediated sflt-1
      expression. In vivo gene therapy thus appears to be a feasible approach to the
      clinical management of CNV in conditions such as age-related macular
      degeneration.

PMID- 20053140
TI  - The role of pemetrexed as maintenance treatment in advanced NSCLC: a Phase III
      randomized trial.
AB  - A randomized Phase III trial tested the efficacy of pemetrexed as maintenance
      treatment in patients with advanced non-small-cell lung cancer (NSCLC) who were
      without progression after completing four cycles of first-line platinum-based
      chemotherapy. The primary endpoint of the trial was progression-free survival
      (PFS). Pemetrexed was significantly better than placebo both in terms of PFS and
      overall survival. The study was not designed as a direct comparison between
      'early' and 'delayed' administration of pemetrexed because there was no mandatory
      cross-over in the control arm, in which less than 20% of patients actually
      received pemetrexed as second-line. However, a relevant proportion of patients
      with advanced NSCLC, due to early death or clinical deterioration, will never be
      able to receive a second-line treatment after disease progression. At the end of
      first-line treatment, the immediate administration of a drug that has not been
      received before (instead of adopting the 'wait and watch' approach based on
      stopping treatment until disease progression) could be a positive strategy,
      allowing patients to receive early one more potentially active drug without an
      unacceptable increase in toxicity. This strategy should be discussed with
      patients. Prespecified analysis of efficacy by tumor histology showed a
      significant interaction between treatment and histology, with pemetrexed
      producing significant and clinically meaningful benefit compared to placebo in
      the non-squamous group, without efficacy in patients with squamous tumors.

PMID- 20053141
TI  - Chlamydia pneumoniae-specific intrathecal oligoclonal antibody response is
      predominantly detected in a subset of multiple sclerosis patients with
      progressive forms.
AB  - The purpose of this study was to verify the actual involvement of Chlamydia
      pneumoniae in multiple sclerosis (MS) by the evaluation of its specific
      intrathecal humoral immune response in MS. We measured by enzyme-linked
      immunosorbent assay (ELISA) technique cerebrospinal fluid (CSF) and serum levels
      of anti-C. pneumoniae immunoglobulin G (IgG) in 27 relapsing-remitting (RR), 9
      secondary progressive (SP), and 5 primary progressive (PP) MS patients, grouped
      according to clinical and magnetic resonance imaging (MRI) evidence of disease
      activity. Twenty-one patients with other inflammatory neurological disorders
      (OIND) and 21 with noninflammatory neurological disorders (NIND) were used as
      controls. Quantitative intrathecal synthesis of anti-C. pneumoniae IgG was
      determined by antibody-specific index (ASI), whereas the presence of C.
      pneumoniae-specific CSF oligoclonal IgG bands was assessed by antigen-specific
      immunoblotting. ASI values indicative of C. pneumoniae-specific intrathecal IgG
      synthesis were present in a small proportion of MS (29.3%), OIND (33.3%), and
      NIND (4.8%) patients and were significantly more frequent (P < .05) in total MS
      and in OIND than in NIND and in SP (P < .01) and PP MS (P < .05) than in RR MS.
      C. pneumoniae-specific CSF-restricted OCB were detected only in three SP, one PP,
      and one RR MS patients. These findings suggest that an intrathecal production of
      anti-C. pneumoniae IgG is part of humoral polyreactivity driven by MS chronic
      brain inflammation. However, an intrathecal release of C. pneumoniae-specific
      oligoclonal IgG can occur in a subset of patients with MS progressive forms in
      whom a C. pneumoniae-persistent brain infection may play a pathogenetic role.

PMID- 20053142
TI  - Neurocognitive impairment and psychiatric comorbidity in well-controlled human
      immunodeficiency virus-infected Thais from the 2NN Cohort Study.
AB  - This research is a cross-sectional study to determine the frequency of
      neurocognitive impairment and psychiatric comorbidity among Thais maintained on
      highly active antiretroviral therapy (HAART) with undetectable plasma human
      immunodeficiency virus (HIV) RNA in the 2NN Cohort. Sixty-four subjects were
      evaluated with neurological examinations, neuropsychological testing, and
      psychiatric questionnaires. Twenty-four subjects (37.5%) were found to have
      neurocognitive impairment, with 13 (20.3%), 10 (15.6%), and 1 (1.6%) classified
      as asymptomatic neurocognitive disorder (ANI), mild neurocognitive disorder
      (MND), and HIV-associated dementia (HAD), respectively. Three subjects (4.7%) had
      depression and no cases had significant symptoms of anxiety. A notable proportion
      of well-controlled individuals exhibited neurocognitive impairment. Anxiety and
      depression were uncommon.

PMID- 20053143
TI  - Naptumomab estafenatox: a new immunoconjugate.
AB  - IMPORTANCE OF THE FIELD: New agents that specifically engage the immune system
      are being tested in a variety of malignancies. This review provides an overview
      of naptumomab, an immunotoxin, with encouraging clinical activity in Phase I
      trials. AREAS COVERED IN THIS REVIEW: This review examines the preclinical and
      the published clinical data with regards to naptumomab. WHAT THE READER WILL
      GAIN: This review provides the reader with an understanding of the mechanism of
      action, immunology, pharmacokinetics and clinical activity of this agent. TAKE
      HOME MESSAGE: Naptumomab has a unique mechanism of action and appears to be an
      active agent in the treatment of refractory solid tumors such as renal cell
      carcinoma.

PMID- 20053144
TI  - Combination therapy with angiotensin-converting enzyme inhibitors and indapamide
      impairs glucose tolerance in Chinese hypertensive patients.
AB  - BACKGROUND: Elevated blood glucose (BG) induced by antihypertensive agents
      increases the risk of cardiovascular events. This study was designed to
      investigate whether fosinopril+indapamide combination therapy has any effect on
      glucose tolerance (GT), and if it did, whether conversion to fosinopril alone
      could reverse the impaired GT. METHODS: Included in the present study were 124
      hypertensive patients, of whom 62 patients were treated with fosinopril plus
      indapamide (F/I group) and the remaining 62 patients were treated with fosinopril
      alone (F group). Of them, 89 patients completed a mean of 14-month follow-up. In
      the F/I group, 29 patients were converted to the use of fosinopril for 4-12
      months after they completed the follow-up. RESULTS: In the F group, fasting BG
      decreased significantly from 5.1+/-0.5 to 4.8+/-0.7 mmol/l (p<0.01), and 2-h
      postprandial BG decreased significantly from 7.2+/-1.6 to 6.4+/-1.4 mmol/l
      (p<0.01), while in the F/I group, fasting BG increased significantly from 5.1 +/
      0.6 to 5.3+/-0.9 mmol/l (p<0.05), and 2-h postprandial BG increased significantly
      from 7.2+/-1.7 to 7.7+/-1.8 mmol/l (p<0.05). In 29 patients of the F/I group who
      completed the follow-up and were converted to fosinopril, fasting BG decreased
      significantly from 5.5+/-1.0 to 5.3+/-1.0 mmol/l (p<0.05), and 2-h postprandial
      BG decreased significantly from 7.5+/-2.0 to 7.0+/-2.7 mmol/l (p<0.05).
      CONCLUSION: Fosinopril+indapamide combination therapy impaired GT in Chinese
      hypertensive patients, and fosinopril alone was able to reverse
      fosinopril+indapamide-induced GT impairment in part of these patients.

PMID- 20053145
TI  - Liver tissue engineering: promises and prospects of new technology.
AB  - Today, many patients suffer from acute liver failure and hepatoma. This is an
      area of high unmet clinical need as these conditions are associated with very
      high mortality. There is an urgent need to develop techniques that will enable
      liver tissue engineering or generate a bioartificial liver, which will maintain
      or improve liver function or offer the possibility of liver replacement. Liver
      tissue engineering is an innovative way of constructing an implantable liver and
      has the potential to alleviate the shortage of organ donors for orthotopic liver
      transplantation. In this review we describe, from an engineering perspective,
      progress in the field of liver tissue engineering, including three main aspects
      involving cell sources, scaffolds and vascularization.

PMID- 20053147
TI  - Rural-urban differences in overweight and obesity among a large sample of
      adolescents in Ontario.
AB  - OBJECTIVE: Increasing our understanding of the differences between obesity and
      overweight status across various geographical areas may have important public
      health implications. We aimed to explore prevalence and factors (i.e.,
      demographic and lifestyle) associated with overweight and obesity among youth
      across urban, suburban and rural settings. METHODS: A cross-sectional study used
      self-reported data collected from students (grades 9-12) attending 76 high
      schools in Ontario, Canada, as part of the SHAPES-Ontario study (2005-2006). Of
      the 34 578 eligible students selected to complete the Physical Activity Module in
      the 76 participating schools, 73.5% (n=25 416; 50.8% males, 49.2% females)
      completed the survey. Univariate and multivariate analyses were conducted using
      body mass index for weight measurement and self-reported data on lifestyle
      factors, and self-perception of body weight. RESULTS: The overall prevalence of
      overweight and obesity was 14.3% and 6.3%, respectively. The prevalence of
      overweight in urban, suburban and rural areas was 14.6%, 13.8% and 15.1%,
      respectively, while the prevalence of obesity was 6.3%, 6.0% and 6.7%,
      respectively, and the difference was significant (chi(2)= 16.53, p<0.05). In the
      multivariate logistic regression analysis, age, TV watching, level of
      urbanization and perception of body weight were important predictors of
      overweight and obesity. CONCLUSION: Our understanding of how overweight and
      obesity rates vary depending on the level of urbanization may help health
      professionals to either tailor programs to the needs of the individuals living in
      these different areas or to target existing programs to the contexts where they
      are most likely to have an impact.

PMID- 20053148
TI  - Moving towards health. Abstracts of the 19th European Childhood Obesity Group
      Meeting. September 17-17, 2009. Dublin, Ireland.

PMID- 20053146
TI  - Functional assessment of human dendritic cells labeled for in vivo (19)F magnetic
      resonance imaging cell tracking.
AB  - BACKGROUND AIMS: Dendritic cells (DC) are increasingly being used as cellular
      vaccines to treat cancer and infectious diseases. While there have been some
      promising results in early clinical trials using DC-based vaccines, the inability
      to visualize non-invasively the location, migration and fate of cells once
      adoptively transferred into patients is often cited as a limiting factor in the
      advancement of these therapies. A novel perflouropolyether (PFPE) tracer agent
      was used to label human DC ex vivo for the purpose of tracking the cells in vivo
      by (19)F magnetic resonance imaging (MRI). We provide an assessment of this
      technology and examine its impact on the health and function of the DC. METHODS:
      Monocyte-derived DC were labeled with PFPE and then assessed. Cell viability was
      determined by examining cell membrane integrity and mitochondrial lipid content.
      Immunostaining and flow cytometry were used to measure surface antigen expression
      of DC maturation markers. Functional tests included bioassays for interleukin
      (IL)-12p70 production, T-cell stimulatory function and chemotaxis. MRI efficacy
      was demonstrated by inoculation of PFPE-labeled human DC into NOD-SCID mice.
      RESULTS: DC were effectively labeled with PFPE without significant impact on cell
      viability, phenotype or function. The PFPE-labeled DC were clearly detected in
      vivo by (19)F MRI, with mature DC being shown to migrate selectively towards
      draining lymph node regions within 18 h. CONCLUSIONS: This study is the first
      application of PFPE cell labeling and MRI cell tracking using human
      immunotherapeutic cells. These techniques may have significant potential for
      tracking therapeutic cells in future clinical trials.

PMID- 20053149
TI  - Acupuncture and herbal medicine in in vitro fertilisation: a review of the
      evidence for clinical practice.
AB  - The objectives of this systematic review were to determine the effectiveness of
      (a) acupuncture and (b) Chinese herbal medicine on the treatment of male and
      female subfertility by assisted reproductive technologies (ART). All reports from
      RCTs of acupuncture and/or Chinese herbal medicine in ART were obtained via
      searches through The Cochrane Menstrual Disorders and Sub-fertility Group's
      Specialised Register of controlled trials, and other major databases. The outcome
      measures were determined prior to starting the search, and comprised: live birth
      rate, ongoing pregnancy rate, clinical pregnancy rate, the incidence of ovarian
      hyperstimulation syndrome and multiple pregnancy, miscarriage rate and adverse
      effects arising from treatment. Overall, 14 trials (a total of 2670 subjects)
      were included in the meta-analysis. The results provided no evidence of benefit
      in the use of acupuncture during assisted conception. Further studies should
      attempt to explore the potential placebo, as well as treatment, effects of this
      complimentary therapy. Essential elements for a quality RCT will be the size of
      the trial, the use of a standardised acupuncture method and of placebo needles.

PMID- 20053152
TI  - Correlation between hyperacusis measurements in daily ENT practice.
AB  - The aim of this study was to investigate hyperacusis measurement tools and to
      assess the correlation between diagnostic methods for hyperacusis in daily ENT
      practice. We studied two hyperacusis questionnaires: the Hyperacusis
      Questionnaire (HQ) and the Multiple-Activity Scale for Hyperacusis (MASH),
      audiometric measurements (uncomfortable loudness level (ULL) and dynamic range
      (DR)), and the questions 'Do you have a lower tolerance for noise... ?' and 'Are
      you afraid of noise?' Hyperacusis was assessed in 46 patients presenting with
      primary complaints of tinnitus. A validated Dutch version of the HQ is provided.
      A correlation was found between scores on the HQ and the MASH (p=0.000,
      R(2)=0.34). Significantly higher scores for both questionnaires were found in
      patients reporting decreased sound tolerance (p=0.000 and 0.002, respectively) or
      fear of noise (p=0.002 and 0.004, respectively). Overall, no correlations were
      found between scores on questionnaires and audiometric values including ULL and
      DR. The HQ and MASH were confirmed to be valid measurement tools for hyperacusis
      complaints. No correlations were found between audiometric measurements and
      hyperacusis complaints.

PMID- 20053151
TI  - The association of the plasma vasopressin level during attacks with a prognosis
      of Meniere's disease.
AB  - An elevation of the plasma arginine vasopressin (AVP) level has frequently been
      observed in Meniere's disease patients. However, little is known regarding the
      mechanism behind this elevation. The plasma AVP levels in acute phase were
      determined in 21 Meniere's disease patients and 16 patients with other types of
      vertigo. The plasma AVP levels of Meniere's disease patients in the acute phase
      were significantly higher than in those of other vertigo patients (p < 0.01). In
      Meniere's disease patients with abnormally high levels of AVP (more than 3.5
      pg/ml) in the acute phase, 36% of patients were resistant to conservative
      treatments for frequent vertigo attacks for the follow-up period of at least
      2years. A significant correlation was observed between the plasma AVP in the
      acute phase and the highest hearing threshold level at a frequency of 1kHz for
      the follow-up period of at least 1 year (r=0.45, p < 0.05). These results suggest
      that the elevation in plasma AVP level in the acute phase is associated with the
      prognosis of Meniere's disease.

PMID- 20053153
TI  - A multi-site evaluation of a proposed test for verifying hearing aid maximum
      output.
AB  - The aim of this study was to evaluate a clinical test proposed to verify the
      output setting of hearing aids. Across three test sites, 56 bilaterally fitted
      hearing aid users were recruited. They answered questions about real-life
      loudness discomfort experiences and then completed the output verification test.
      Using an ascending method, a 1,500 kHz narrowband noise and a selection of
      broadband environmental noises were presented in 5 dB steps from 80 to 90 dB SPL.
      Response options included 'acceptably loud', and 'uncomfortably loud'. A swept
      pure tone presented at 90 dB SPL was also administered. Some loudness discomfort
      was reportedly experienced in real life by 82% of the participants. Generally,
      the test noises produced low specificity, with the 1,500 kHz narrowband noise
      being the best predictor of loudness discomfort experiences in real life, while
      the swept pure tone showed low sensitivity. Individual reactions to specific
      sounds and the test equipment and environment used are argued to affect the
      laboratory performance. A better understanding of these factors is needed before
      the test can be improved. an ser mejoradas.

PMID- 20053150
TI  - Newer antibacterial drugs for a new century.
AB  - IMPORTANCE OF THE FIELD: Antibacterial drug discovery and development has slowed
      considerably in recent years, with novel classes discovered decades ago and
      regulatory approvals tougher to get. Traditional approaches and the newer genomic
      mining approaches have not yielded novel classes of antibacterial compounds.
      Instead, improved analogues of existing classes of antibacterial drugs have been
      developed by improving potency, minimizing resistance and alleviating toxicity.
      AREAS COVERED IN THIS REVIEW: This article is a comprehensive review of newer
      classes of antibacterial drugs introduced or approved after year 2000. WHAT THE
      READER WILL GAIN: It describes their mechanisms of action/resistance, improved
      analogues, spectrum of activity and clinical trials. It also discusses new
      compounds in development with novel mechanisms of action, as well as novel
      unexploited bacterial targets and strategies that may pave the way for combating
      drug resistance and emerging pathogens in the twenty-first century. TAKE HOME
      MESSAGE: The outlook of antibacterial drug discovery, though challenging, may not
      be insurmountable in the years ahead, with legislation on incentives and funding
      introduced for developing an antimicrobial discovery program and efforts to
      conserve antibacterial drug use.

PMID- 20053154
TI  - Caffeine abstinence: an ineffective and potentially distressing tinnitus therapy.
AB  - The effect of phased caffeine withdrawal and abstention on tinnitus severity was
      assessed using a pseudo-randomized, double-blinded, placebo-controlled crossover
      trial of 30 days duration. Sixty-six volunteers who experienced tinnitus and who
      usually consumed at least 150 mg/day of caffeine participated. The intervention
      was a direct replacement of usual caffeinated tea/coffee with double-blinded
      supplies, under one of two conditions. Condition 1: Maintenance followed by
      phased withdrawal. Condition 2: Phased withdrawal followed by reintroduction and
      maintenance. Tinnitus severity was measured by the total score of the Tinnitus
      Questionnaire on Days 1, 15, and 30. Secondary measures included twice daily self
      rated symptoms relevant to tinnitus and caffeine withdrawal. Caffeine had no
      effect on tinnitus severity, the mean difference between caffeinated and
      decaffeinated days being -0.04 (95% confidence interval -1.99 to 1.93), p=0.97.
      Significant acute adverse symptoms of caffeine withdrawal were observed. No
      evidence was found to justify caffeine abstinence as a therapy to alleviate
      tinnitus, but acute effects of caffeine withdrawal might add to the burden of
      tinnitus.

PMID- 20053155
TI  - Multi-site diagnosis and management of 260 patients with auditory neuropathy/dys
      synchrony (auditory neuropathy spectrum disorder).
AB  - Test results and management data are summarized for 260 patients with diagnoses
      of Auditory Neuropathy Spectrum Disorder (ANSD). Hearing aids were tried in 85 of
      these patients, and 49 patients tried cochlear implants. Approximately 15%
      reported some benefit from hearing aids for language learning, while improvement
      in speech comprehension and language acquisition was reported in 85% of patients
      who were implanted. Approximately 5% (13/260) of the total population developed
      normal speech and language without intervention. Patients were diagnosed at our
      laboratory (n=66) or referred from other sites (n=194), and all showed
      absent/grossly abnormal auditory brainstem responses (ABR), often 'ringing'
      cochlear microphonics, and the presence or history of otoacoustic emissions.
      Etiologies and co-existing conditions included genetic (n=41), peripheral
      neuropathies (n=20), perinatal jaundice and/or anoxia and/or prematurity (n=74).
      These patients comprise 10% or more of hearing impaired patients; their language
      acquisition trajectories are generally unpredictable from their audiograms.

PMID- 20053156
TI  - Users' perspectives on the benefits of FM systems with cochlear implants.
AB  - This study explored: (1) the benefits of an FM system in real-world environments
      from the perspective of adults with coch-lear implants, and (2) the factors and
      barriers to using an FM system with a cochlear implant. Using a qualitative
      research design, 14 adults with unilateral cochlear implants recorded their
      experiences during a two-month trial period with a personal FM system and
      responded to a questionnaire at the end of the trial. A detailed analysis of 169
      journal entries (230 hours of FM use) permitted a description of the benefits and
      negative aspects associated with FM use in everyday listening environments. The
      primary benefits were related to improved access to and quality of sound,
      improved distance listening, ease of listening, and better social integration.
      Negative perceptions were associated with the equipment both with regard to
      physical aspects and adjustments. In addition, technical, individual, social, and
      environmental factors were identified that can influence the user's decision to
      use the FM device. Questionnaire responses indicated that the majority of
      individuals rated the FM system as somewhat or very helpful. The findings suggest
      that FM systems can improve communication in everyday listening environments for
      some adults with cochlear implants.

PMID- 20053157
TI  - Maternal infection with toxoplasma gondii in pregnancy and the risk of hearing
      loss in the offspring.
AB  - The aim of this study was to investigate the association between maternal
      infection with Toxoplasma gondii (T. gondii) in pregnancy and subsequent risk of
      hearing loss in the offspring. The study included 27 727 children born in Norway
      1992-1994. Maternal toxoplasma infection during pregnancy was ascertained by
      serological examination and fetal infection was ascertained by parasite detection
      in amniotic fluid and/or postnatal serological examination. Hearing loss was
      defined as mean hearing loss >35 dB HL in the better ear averaged over the pure
      tone hearing thresholds at 500, 1000, and 2000 Hz, and the children were
      identified through linkage to the Norwegian Registry of Hearing Loss in Children.
      Twenty-two of the 27 727 children (0.08%) were diagnosed with hearing loss. Forty
      women had primary T. gondii infection in pregnancy. None of their offspring had
      hearing loss. There was also no association between T. gondii infection prior to
      pregnancy and hearing loss in the offspring. Hence, we did not find any
      association between T. gondii infection in pregnancy and hearing loss in the
      offspring.

PMID- 20053158
TI  - A comparison of three approaches to verifying aided Baha output.
AB  - OBJECTIVE: The objective of the present study was to compare three methods of
      estimating the audibility of aided speech using the Baha. SUBJECTS: 23 Adult Baha
      users with primarily bilateral conductive hearing loss were recruited from the
      Bone Conduction Amplification Program at the Institute for Reconstructive
      Sciences in Medicine in Edmonton, Alberta, Canada. METHODS: A test Baha was set
      to each subject's preferred listening level. The same Baha was used to assess the
      audibility of the long-term average speech spectrum (LTASS) for each of the
      following three approaches: 1) Aided soundfield thresholds, 2) Real Ear SPL, and
      3) Real Head Acceleration Level. RESULTS: Significant differences were discovered
      between the three approaches. Aided soundfield thresholds consistently over
      estimated the sensation level of aided speech. The Real Ear SPL approach provided
      reasonable estimates in the mid-frequencies. However, low- and high-frequency
      estimates for the Real Ear approach have significant limitations. CONCLUSIONS:
      The Real Head Acceleration Level appears to be the most accurate method of
      determining aided audibility with the Baha.

PMID- 20053159
TI  - The malignant psoas syndrome revisited: case report, mechanisms, and current
      therapeutic options.
AB  - The malignant psoas syndrome (MPS) is a rare and challenging cancer pain state
      that is often refractory to rational polymodal analgesic therapy. We describe the
      first case of cervix cancer-related MPS due to extrinsic psoas muscle
      infiltration and review the therapeutic trajectory and outcome. The anatomic
      determinants, pain mechanisms, and current and proposed novel treatment
      strategies for MPS are discussed.

PMID- 20053160
TI  - Evaluation of drug transporter interactions in drug discovery and development.
AB  - Drug transporters play an important role in the absorption, distribution,
      excretion and toxicity of both endogenous and exogenous compounds. Transporters
      may act as physiological 'gatekeepers' in the regulation of the pharmacological
      and/or toxicological effects of drugs by limiting distribution to tissues
      responsible for their effect and/or toxicity. This review will first provide a
      brief outline of the characteristics of membrane bound drug transporter families
      and their respective roles in regulating drug pharmacokinetics. This background
      then provides the context for a discussion of the characterization of a drug
      candidate as a substrate, inhibitor and/or inducer of drug transporter(s),
      followed by an assessment of the in vitro and in vivo preclinical methods used in
      drug discovery and development for screening molecules to identify potential
      transporter interactions. Finally, specific examples of the translation of in
      vitro findings to the in vivo effects are discussed to link the current
      understanding of the impact of drug transporters to clinical pharmacology. Thus,
      the goal is to provide the drug discovery scientist with a cadre of concepts,
      strategies, and tools for ultimately making rational decisions in drug design and
      delivery resulting in the optimization of drug concentrations at the target of
      pharmacology.

PMID- 20053161
TI  - Enzyme induction: translating multiple approaches, assays, endpoints, and
      opinions into a valuable induction screening strategy.
AB  - Drug metabolizing enzyme induction, or the process of generating excess drug
      metabolizing enzyme in important tissues of drug disposition such as liver and
      intestine, can give rise to pharmacokinetic situations whereby drug interactions
      occur. There are two major concerns associated with enzyme induction. First is
      the potential loss of efficacy due to more rapid metabolism and second is the
      risk of an increase in the formation of a potential reactive/toxic metabolite.
      Because of this, pharmaceutical companies consider enzyme induction as an
      undesired drug property for their potential drug candidates. As a consequence,
      the number of tools and models to evaluate induction of drug metabolizing enzymes
      has been increased tremendously over the past decade. As often is the case, every
      assay and approach has its own advantages and disadvantages and unfortunately, no
      single tool is currently available to predict the induction potential of drug
      candidates in humans. The purpose of this review is not only to outline the
      screening tools currently available for determining the induction potential of
      new chemical entities but also to translate these tools into a valuable screening
      strategy, covering aspects such as, induction liability assessment, structure
      activity relationships (SAR), induction risk assessment and translating in vitro
      findings into clinical relevance.

PMID- 20053162
TI  - Plasma protein binding in drug discovery and development.
AB  - This review describes methods for quantifying the binding of small molecule drug
      candidates to plasma proteins and the application of these methods in drug
      discovery and development. Particular attention is devoted to methods amenable to
      medium-to-high throughput analysis and those well suited for measurement of
      compounds that are highly protein bound. The methods reviewed herein include the
      conventional techniques of equilibrium dialysis, ultrafiltration and
      ultracentrifugation, as well as some more novel approaches utilizing
      micropartitioning and biosensor-based analysis. Additional concepts that are
      discussed include plasma protein structure, enantioselective protein binding,
      drug displacement, the effect of patient demographics and disease states on free
      (unbound) drug levels, and the influence of protein binding on drug candidate
      pharmacokinetics and pharmacodynamics. Practical considerations pertaining to the
      evaluation of highly protein bound drug candidates are also highlighted.

PMID- 20053163
TI  - Building a tiered approach to in vitro predictive toxicity screening: a focus on
      assays with in vivo relevance.
AB  - One of the greatest challenges facing the pharmaceutical industry today is the
      failure of promising new drug candidates due to unanticipated adverse effects
      discovered during preclinical animal safety studies and clinical trials. Late
      stage attrition increases the time required to bring a new drug to market,
      inflates development costs, and represents a major source of inefficiency in the
      drug discovery/development process. It is generally recognized that early
      evaluation of new drug candidates is necessary to improve the process. Building
      in vitro data sets that can accurately predict adverse effects in vivo would
      allow compounds with high risk profiles to be deprioritized, while those that
      possess the requisite drug attributes and a lower risk profile are brought
      forward. In vitro cytotoxicity assays have been used for decades as a tool to
      understand hypotheses driven questions regarding mechanisms of toxicity. However,
      when used in a prospective manner, they have not been highly predictive of in
      vivo toxicity. Therefore, the issue may not be how to collect in vitro toxicity
      data, but rather how to translate in vitro toxicity data into meaningful in vivo
      effects. This review will focus on the development of an in vitro toxicity
      screening strategy that is based on a tiered approach to data collection combined
      with data interpretation.

PMID- 20053164
TI  - Preformulation designed to enable discovery and assess developability.
AB  - Physicochemical properties of drug molecules impact many aspects of both in vivo
      and in vitro behavior. Poor physicochemical properties can often create a
      significant impediment to establishing reliable SAR, establishing proof of
      principle type studies using in vivo models, and eventually leading to added
      performance variability and costs throughout the development life cycle; in the
      worst case scenario, even preventing execution of the desired development plan.
      Understanding the fundamental physicochemical properties provides the basis to
      dissect and deconvolute experimental observations in such a way that modification
      or mitigation of poor molecular properties can be impacted at the design phase,
      insuring design and selection of a molecule which has a high probability of
      making it through the arduous development cycle. This review will discuss the key
      physicochemical properties and how they can be assessed and how they are
      implicated in both discovery enablement and in final product developability of
      the selected candidate.

PMID- 20053165
TI  - Solubility and permeability measurement and applications in drug discovery.
AB  - Solubility and cellular permeability are two of the most important
      biopharmaceutical properties impacting the successful development of drug
      substances. Given the importance of these properties, most pharmaceutical
      companies have invested in medium to high throughput technologies for early
      evaluation of these characteristics in the drug discovery funnel in order to
      select, prioritize or eliminate compounds with unfavorable solubility and/or
      permeability. However, these technologies require physical samples of the
      substances to be tested. In order to facilitate the early stages of drug
      discovery, such as defining compound collection composition, designing
      combinatorial libraries, and in hit expansion or lead optimization, models for
      predicting aqueous solubility and permeability in the absence of physical sample
      are increasingly being employed. In this overview, we will discuss solubility and
      permeability experimental and computational methods separately and then
      interrelate them in physiologically relevant models for predicting in vivo
      performance.

PMID- 20053166
TI  - Application of in vivo animal models to characterize the pharmacokinetic and
      pharmacodynamic properties of drug candidates in discovery settings.
AB  - A goal of preclinical discovery is the identification of drug candidates suitable
      for clinical testing. Successful integration of in vitro and in vivo experimental
      data sets can afford projections of human dose regimens anticipated to be safe
      and therapeutically beneficial. While in vitro experiments guide new chemical
      syntheses and are essential to understanding drug action and disposition, in vivo
      characterizations provide unique insight into complex biological systems that
      control concentrations at the site of action and pharmacologic response.
      Pharmacokinetic and pharmacodynamic (PK/PD) concepts underlying drug disposition
      and response provide a quantitative framework with which to identify potential
      clinical candidates. To improve throughput in earlier stages of drug discovery,
      in vivo pharmacokinetic study designs such as cassette dosing and sparse sampling
      schemes have been utilized. In later stages of discovery, pharmacokinetic studies
      using chemical inhibitors or surgical and genetic animal models are used to
      characterize the underlying determinants of drug disposition. In a complimentary
      fashion, modeling of in vivo pharmacodynamic effects may quantitatively link
      biomarkers to pharmacological response, validate in vitro to in vivo correlations
      and underwrite predictions of efficacious exposure targets. When applied to in
      vivo discovery data, PK/PD models have aided in understanding mechanisms of
      pharmacological response such as receptor theory in the central nervous system
      and cell turnover concepts in infectious disease and oncology. This review
      considers the role of in vivo testing toward understanding the pharmacokinetic
      and pharmacodynamic attributes of lead candidates in drug discovery.

PMID- 20053167
TI  - Scaling in vivo pharmacokinetics from in vitro metabolic stability data in drug
      discovery.
AB  - In this review, the current approach to predicting hepatic clearance from in
      vitro metabolic systems is discussed along with a survey of current industry
      practice. The definitive method of determining intrinsic clearance remains the
      measurement of Michaelis-Menten parameters derived from metabolite formation rate
      data. However, in drug discovery this method has limitations which result in the
      method most commonly applied being the half-life method utilizing a single, low
      substrate concentration. Additionally, the importance of correcting in vitro
      intrinsic clearance values for futile binding within the incubation has become
      accepted, although the majority of the respondents to the industry survey do not
      currently correct for this. It is also apparent that most investigators employ
      standard incubation conditions for determining intrinsic clearance which may not
      be appropriate for all compounds. Adapting these conditions to vary both the
      substrate and enzyme concentrations offers a relatively simple method to gain
      useful information regarding potential Km values and in vitro futile binding.
      Although there are many factors that influence the relationship between intrinsic
      clearance and hepatic clearance, even in a discovery setting opportunities exist
      for limited tailoring of assay conditions, which when combined with some
      judicious assumptions and forethought, make it possible to use intrinsic
      clearance values in a rational manner to identify compounds with the desired
      pharmacokinetic properties.

PMID- 20053168
TI  - Application of cytochrome P450 drug interaction screening in drug discovery.
AB  - Advances in drug interaction screening have resulted in reduced compound
      attrition rates due to unfavorable CYP-mediated drug interactions in clinical
      trials and improved patient safety. A major driver for the success in predicting
      drug interactions is a better understanding of the biological, chemical or
      mechanical factors that can impact the prediction of drug interactions in vitro.
      The enzyme source, probe substrate, accessory proteins and pharmacogenetics can
      all have profound effects upon the robustness and relevance of data generated
      with in vitro drug-drug interaction assays. Furthermore, the use of in silico
      techniques can potentially afford a priori knowledge of drug interaction
      potential, thus reducing the time and cost associated with drug interaction
      screening. This review will focus on recent advances in in vitro, in silico and
      bioanalytical techniques and demonstrate how these tools are currently used to
      provide effective CYP drug interaction screening in a discovery setting.

PMID- 20053169
TI  - Mechanisms of oxidative glutamate toxicity: the glutamate/cystine antiporter
      system xc- as a neuroprotective drug target.
AB  - The glutamate/cystine antiporter system x(c)- transports cystine into cells in
      exchange for the important neurotransmitter glutamate at a ratio of 1:1. It is
      composed of a specific light chain, xCT, and a heavy chain, 4F2, linked by a
      disulfide bridge. Both subunits are localized prominently in the mouse and human
      brain especially in border areas between the brain and periphery including
      vascular endothelial cells, ependymal cells, choroid plexus, and leptomeninges.
      Glutamate exported by system x(c)- is largely responsible for the extracellular
      glutamate concentration in the brain, whereas the imported cystine is required
      for the synthesis of the major endogenous antioxidant, glutathione. System x(c)-
      thus connects the antioxidant defense with neurotransmission and behavior.
      Disturbances in the function of system x(c)- have been implicated in nerve cell
      death due to increased extracellular glutamate and reduced intracellular
      glutathione. In vitro, inhibition of cystine import through system x(c)- leads to
      cell death by a mechanism called oxidative glutamate toxicity or oxytosis, which
      includes depletion of intracellular glutathione, activation of 12-lipoxygenase,
      accumulation of intracellular peroxides, and the activation of a cyclic guanosine
      monophosphate (cGMP)-dependent calcium channel towards the end of the death
      cascade. Cell death caused by oxytosis is distinct from classical apoptosis. In
      this contribution, we discuss the function of system x(c)- in vitro and in vivo,
      the role of xCT as an important but due to its dual role probably ambivalent drug
      target, and the relevance of oxytosis as an in vitro assay for the identification
      of novel neuroprotective proteins and signaling pathways.

PMID- 20053170
TI  - Treating schizophrenia: novel targets for the cholinergic system.
AB  - Cognitive deficits in patients with schizophrenia are the biggest obstacle to
      achieving an independent and productive lifestyle, with these deficits being
      refractory to current drug treatments. Significantly, both nicotinic and
      muscarinic receptors (cholinoceptors) have been shown to have an important role
      in cognition and are therefore viewed as potential therapeutic targets for drugs
      designed to lessen cognitive deficits. Importantly, the demonstration that
      acetylcholinesterase inhibitors, which result in higher synaptic levels of
      acetylcholine, can reduce the cognitive deficits of schizophrenia suggested that
      under-stimulation of cholinoceptors could be associated with the cognitive
      deficits associated with this disorder. This has lead to a focus on the
      development of receptor agonists, partial agonists and allosteric agonists that
      can be used to stimulate cholinergic pathways and thus reduce the cognitive
      deficits of schizophrenia. In addition, muscarinic receptors have now been
      associated with the modulation of dopamine and may constitute an alternative
      target for the treatment of psychoses. Given these exciting new therapeutic
      initiatives, this review will outline current evidence that involves the
      cholinoceptors in the pathophysiology of schizophrenia and how these data can
      inform on approaches to more targeted treatments for the disorder.

PMID- 20053181
TI  - Metal ion effects on hydraulic conductivity of bacterial cellulose-pectin
      composites used as plant cell wall analogs.
AB  - Low concentrations of some trace metals markedly reduce root elongation rate and
      cause ruptures to root rhizodermal and outer cortical cells in the elongation
      zone. The interactions between the trace metals and plant components responsible
      for these effects are not well understood but may be linked to changes in water
      uptake, cell turgor and cell wall extensibility. An experiment was conducted to
      investigate the effects of Al, La, Cu, Gd, Sc and Ru on the saturated hydraulic
      conductivity of bacterial cellulose (BC)-pectin composites, used as plant cell
      wall analogs. Hydraulic conductivity was reduced to approximately 30% of the
      initial flow rate by 39 microM Al and 0.6 microM Cu, approximately 40% by 4.6
      microM La, 3 microM Sc and 4.4 microM Ru and approximately 55% by 3.4 microM Gd.
      Scanning electron microscopy (SEM) revealed changes in the ultrastructure of the
      composites. The results suggest that trace metal binding decreases the hydraulic
      conductivity through changes in pectin porosity. The experiment illustrates the
      importance of metal interactions with pectin, and the implications of such an
      interaction in plant metal toxicity and in normal cell wall processes.

PMID- 20053182
TI  - Constitutive activation of stress-inducible genes in a brassinosteroid
      insensitive 1 (bri1) mutant results in higher tolerance to cold.
AB  - Many plant hormones are involved in coordinating the growth responses of plants
      under stress. However, not many mechanistic studies have explored how plants
      maintain the balance between growth and stress responses. Brassinosteroids (BRs),
      plant-specific steroid hormones, affect many aspects of plant growth and
      development over a plant's lifetime. In this study we determined that exogenous
      treatment of BR helped the plant overcome the cold condition only when pretreated
      with less than 1 nM, and the brassinosteroid-insensitive 1 (bri1) mutation, which
      results in defective BR signaling and subsequent dwarfism, generates an increased
      tolerance to cold. In contrast, BRI1-overexpressing plants were more sensitive to
      the same stress than wild-type. We found that the bri1 mutant and BRI1
      overexpressing transgenic plants contain higher basal level of expression of
      CBFs/DREB1s than wild-type. However, representative cold stress-related genes
      were regulated with the same pattern to cold in wild-type, bri1-9 and BRI1
      overexpressing plants. To examine the global gene expression and compare the
      genes that show differential expression pattern in bri1-9 and BRI1-GFP plants
      other than CBFs/DREB1s, we analyzed differential mRNA expression using the cDNA
      microarray analysis in the absence of stress. Endogenous expression of both
      stress-inducible genes as well as genes encoding transcription factors that drive
      the expression of stress-inducible genes were maintained at higher levels in bri1
      9 than either in wild-type or in BRI1 overexpressing plants. This suggests that
      the bri1-9 mutant could always be alert to stresses that might be exerted at any
      times by constitutive activation of subsets of defense.

PMID- 20053183
TI  - Aluminum resistance in common bean (Phaseolus vulgaris) involves induction and
      maintenance of citrate exudation from root apices.
AB  - Two common bean (Phaseolus vulgaris L.) genotypes differing in aluminum (Al)
      resistance, Quimbaya (Al-resistant) and VAX-1 (Al-sensitive) were grown in
      hydroponics for up to 25 h with or without Al, and several parameters related to
      the exudation of organic acids anions from the root apex were investigated. Al
      treatment enhanced the exudation of citrate from the root tips of both genotypes.
      However, its dynamic offers the most consistent relationship between Al-induced
      inhibition of root elongation and Al accumulation in and exclusion from the root
      apices. Initially, in both genotypes the short-term (4 h) Al-injury period was
      characterized by the absence of citrate efflux independent of the citrate content
      of the root apices, and reduction of cytosolic turnover of citrate conferred by a
      reduced Nicotinamide adenine dinucleotide phosphate-isocitrate dehydrogenase (EC
      1.1.1.42) activity. Transient recovery from initial Al stress (4-12 h) was found
      to be dependent mainly on the capacity to utilize internal citrate pools (Al
      resistant genotype Quimbaya) or enhanced citrate synthesis [increased activities
      of NAD-malate dehydrogenase (EC 1.1.1.37) and ATP-phosphofructokinase (EC
      2.7.1.11) in Al-sensitive VAX-1]. Sustained recovery from Al stress through
      citrate exudation in genotype Quimbaya after 24 h Al treatment relied on
      restoring the internal citrate pool and the constitutive high activity of citrate
      synthase (CS) (EC 4.1.3.7) fuelled by high phosphoenolpyruvate carboxylase (EC
      4.1.1.31) activity. In the Al-sensitive genotype VAX-1 the citrate exudation and
      thus Al exclusion and root elongation could not be maintained coinciding with an
      exhaustion of the internal citrate pool and decreased CS activity.

PMID- 20053186
TI  - Urosepsis and bacteraemia caused by antibiotic-resistant organisms after
      transrectal ultrasonography-guided prostate biopsy.

PMID- 20053187
TI  - Gene polymorphisms and prostate cancer: the evidence.
AB  - OBJECTIVE: Prostate cancer is still the most frequent noncutaneous male
      malignancy and is the second most common cause of cancer death. Genetic factors
      have been extensively studied in different countries. In addition, numerous
      genome-wide association studies have been performed in developed countries.
      Genetic tests will be applied in the near future for diagnosis, therapeutic, and
      prognostic significance. Therefore, we reviewed the association of several
      important pathways and genes with critical functions in prostate cancer
      development or progression. MATERIALS AND METHODS: We performed a PubMed search
      using several key words such as prostate cancer, names of important genes with
      critical function, and polymorphisms. Then, we reviewed retrieved articles as
      well as relevant articles from 1997 to 2009. RESULTS: There are conflicting
      results of studies on some gene polymorphisms in association with prostate
      cancer. Most of the inconsistent results have been reported in studies
      investigating the vitamin D receptor gene polymorphism in association with
      prostate cancer. Genes related to angiogenesis and cell adhesion genes are more
      promising. Following results of future studies, the use of antibodies blocking
      over-expressed genes or proteins may be supported in patients with prostate
      cancer. CONCLUSIONS: The difference between the results of studies on gene
      polymorphisms in prostate cancer may be explained partly by ethnic differences,
      limited sample size, and other risk or protective factors modifying these
      effects. Genome-wide studies are currently performed in developed countries and
      extensive use of this type of analysis may merit consideration in other
      countries. Furthermore, future studies are needed to further investigate
      environmental and diet factors interactions with genetic factors.

PMID- 20053188
TI  - Preserving bone health in patients with hormone-sensitive prostate cancer: the
      role of bisphosphonates.
AB  - Men with prostate cancer initiating androgen-deprivation therapy (ADT) may have
      multiple factors that threaten their skeletal health, including increased
      fracture risk from bone loss during ADT and the propensity to develop bone
      metastases, which may lead to skeletal-related events (SREs). Bisphosphonates
      have utility in oncology for patients with bone metastases to prevent bone loss
      during hormonal therapy and in the benign setting to treat osteoporosis. These
      agents have an emerging role in patients with hormone-sensitive prostate cancer
      (HSPC). Etidronate, alendronate, pamidronate, and zoledronic acid have all shown
      efficacy in preventing ADT-related bone loss. Alendronate and zoledronic acid
      have also been shown to increase bone mineral density vs baseline during ADT.
      Patients with bone metastases from HSPC who received 4 mg zoledronic acid every 3
      or 4 weeks had a low incidence of skeletal complications, although controlled
      study data have not been reported. Bisphosphonate treatment in men with HSPC may
      be effective for the prevention of ADT-related bone loss, underscoring the
      importance of treating early to avoid SREs and potentially delay disease
      progression to metastatic bone disease.

PMID- 20053189
TI  - Abarelix and other gonadotrophin-releasing hormone antagonists in prostate
      cancer.
AB  - Hormonal therapy is the main recommended treatment for locally advanced and
      metastatic prostate cancer. Luteinizing hormone-releasing hormone (LHRH)
      agonists, such as buserelin, goserelin, leuprorelin and triptorelin, stimulate
      the pituitary's gonadotrophin-releasing hormone (GnRH) receptor, ultimately
      leading to its de-sensitization and subsequent reduction of LH and testosterone
      levels. However, this reduction is accompanied by a well described increase or
      'surge' in LH and testosterone levels, necessitating the concomitant
      administration of an antiandrogen to combat the potential effects of transient
      acceleration in cancer activity. Two pure GnRH antagonists have been developed,
      abarelix and degarelix, that are devoid of any agonist effect on the GnRH
      receptor and consequently do not result in testosterone flare. Abarelix was the
      first GnRH antagonist to be developed and was approved by the USA Food and Drug
      Administration in 2004 for the initiation of hormonal castration in advanced or
      metastasizing hormone-dependent prostate carcinoma, when rapid androgen
      suppression is necessary. Clinical data on both abarelix and degarelix show that
      they can produce rapid and sustained decreases in testosterone to castrate levels
      without the need for co-administration of an antiandrogen, and with a very low
      complication rate in the short term.

PMID- 20053190
TI  - Vascular endothelial growth factor and mTOR pathways in renal cell carcinoma:
      differences and synergies of two targeted mechanisms.
AB  - Renal cell carcinoma (RCC) is among the most resistant tumours to chemotherapy,
      radiotherapy and hormonal therapy. Cytokine therapy is effective in a small
      subset of patients, but it is associated with substantial toxicity and rarely
      benefits patients with extensive tumour burdens or adverse prognostic factors.
      Since 2005, clinical trials have shown significant clinical benefits for five
      molecularly targeted therapies in patients with advanced RCC. These agents
      constitute two mechanistic classes: (i) angiogenesis inhibitors targeting the
      vascular endothelial growth factor (VEGF) ligand (bevacizumab, in combination
      with interferon-a) or VEGF receptors (sunitinib, sorafenib); and (ii) inhibitors
      of the mammalian target of rapamycin (mTOR) signalling (temsirolimus,
      everolimus). This review assesses the mechanistic distinctions and functional
      overlaps of these classes of agents, and discusses key characteristics of their
      respective clinical efficacy and side-effect profiles in patients with RCC, some
      of which might affect patient selection and treatment strategies. Current
      research is designed to optimize the use of these agents, as well as the
      development of new investigational therapies within these mechanistic classes.
      The differences and synergies are particularly important for understanding the
      best ways to integrate VEGF/VEGF receptor inhibitors and mTOR inhibitors for
      combination or sequential treatment of patients with advanced RCC.

PMID- 20053191
TI  - Therapy required for sexual medicine research?

PMID- 20053194
TI  - High-intensity focused ultrasound for localized prostate cancer: initial
      experience with a 2-year follow-up.

PMID- 20053195
TI  - Single-port 'scarless' laparoscopic nephrectomies: the United kingdom experience.

PMID- 20053197
TI  - What would truly patient-centred urological care look like?

PMID- 20053198
TI  - Radical retropubic cystectomy.

PMID- 20053202
TI  - Council of Emergency Medicine Residency Directors/Academic Emergency Medicine
      supplement - the inaugural edition.

PMID- 20053203
TI  - Service versus education: finding the right balance: a consensus statement from
      the Council Of Emergency Medicine Residency Directors 2009 Academic Assembly
      "Question 19" working group.
AB  - Many emergency medicine (EM) residency programs have recently received citations
      for their residents' responses to Question 19 of the Accreditation Council on
      Graduate Medical Education annual survey, which asks residents to rate their
      program's emphasis on clinical education over service obligations. To the best of
      our knowledge, no prior investigations or consensus statements exist that
      specifically address the appropriate balance between educational activity and
      clinical service in EM residency training. The objective of this project was to
      create a consensus statement based on the shared insights of academic faculty and
      educators in EM, with specific recommendations to improve the integration of
      education with clinical service in EM residency training programs. More than 80
      EM program directors (PDs), associate and assistant PDs, and other academic EM
      faculty attending an annual conference of EM educators met to address this issue
      in a discussion session and working group. Participants examined the current
      literature on resident service and education and shared with the conference at
      large their collective insight and experience and possible solutions to this
      challenge. A consensus statement of specific recommendations and effective
      educational techniques aimed at balancing service and education requirements was
      created, based on the contributions of a diverse group of academic emergency
      physicians. Recommendations included identifying the teachable moment in all
      clinical service; promoting resident understanding of program goals and
      expectations from the beginning; educating residents about the ACGME resident
      survey; and engaging hospitals, institutional graduate medical education
      departments, and residents in finding solutions.

PMID- 20053204
TI  - Teaching across the generation gap: a consensus from the Council of Emergency
      Medicine Residency Directors 2009 academic assembly.
AB  - BACKGROUND: Four distinct generations of physicians currently coexist within the
      emergency medicine (EM) workforce, each with its own unique life experience,
      perspective, attitude, and expectation of work and education. To the best of our
      knowledge, no investigations or consensus statements exist that specifically
      address the effect of intergenerational differences on undergraduate and graduate
      medical education in EM. OBJECTIVES: To review the existing literature on
      generational differences as they pertain to workforce expectations, educational
      philosophy, and learning styles and to create a consensus statement based on the
      shared insights of experienced educators in EM, with specific recommendations to
      improve the effectiveness of EM residency training programs. METHODS: A group of
      approximately one hundred EM program directors (PDs), assistant PDs, and other
      academic faculty attending an annual conference of emergency physician (EP)
      educators gathered at a breakout session and working group to examine the
      literature on intergenerational differences, to share insights and discuss
      interventions tailored to address these stylistic differences, and to formulate
      consensus recommendations. RESULTS: A set of specific recommendations, including
      effective educational techniques, was created based on literature from other
      professions and medical disciplines, as well as the contributions of a diverse
      group of EP educators. CONCLUSIONS: Recommendations included early establishment
      of clear expectations and consequences, emphasis on timely feedback and
      individualized guidance during training, explicit reinforcement of a patient
      centered care model, use of peer modeling and support, and emphasis on more
      interactive and small-group learning techniques.

PMID- 20053206
TI  - Alternatives to the conference status quo: summary recommendations from the 2008
      CORD Academic Assembly Conference Alternatives workgroup.
AB  - Abstract Objective: A panel of Council of Emergency Medicine Residency Directors
      (CORD) members was asked to examine and make recommendations regarding the
      existing Accreditation Council of Graduate Medical Education (ACGME) EM Program
      Requirements pertaining to educational conferences, identified best practices,
      and recommended revisions as appropriate. METHODS: Using quasi-Delphi technique,
      30 emergency medicine (EM) residency program directors and faculty examined
      existing requirements. Findings were presented to the CORD members attending the
      2008 CORD Academic Assembly, and disseminated to the broader membership through
      the CORD e-mail list server. RESULTS: The following four ACGME EM Program
      Requirements were examined, and recommendations made: 1. The 5 hours/week
      conference requirement: For fully accredited programs in good standing, outcomes
      should be driving how programs allocate and mandate educational time. Maintain
      the 5 hours/week conference requirement for new programs, programs with
      provisional accreditation, programs in difficult political environs, and those
      with short accreditation cycles. If the program requirements must retain a
      minimum hours/week reference, future requirements should take into account
      varying program lengths (3 versus 4 years). 2. The 70% attendance requirement:
      Develop a new requirement that allows programs more flexibility to customize
      according to local resources, individual residency needs, and individual resident
      needs. 3. The requirement for synchronous versus asynchronous learning:
      Synchronous and asynchronous learning activities have advantages and
      disadvantages. The ideal curriculum capitalizes on the strengths of each through
      a deliberate mixture of each. 4. Educationally justified innovations: Transition
      from process-based program requirements to outcomes-based requirements.
      CONCLUSIONS: The conference requirements that were logical and helpful years ago
      may not be logical or helpful now. Technologies available to educators have
      changed, the amount of material to cover has grown, and online on-demand
      education has grown even more. We believe that flexibility is needed to customize
      EM education to suit individual resident and individual program needs, to
      capitalize on regional and national resources when local resources are limited,
      to innovate, and to analyze and evaluate interventions with an eye toward
      outcomes.

PMID- 20053207
TI  - Resident training in emergency ultrasound: consensus recommendations from the
      2008 Council of Emergency Medicine Residency Directors Conference.
AB  - Over the past 25 years, research performed by emergency physicians (EPs)
      demonstrates that bedside ultrasound (US) can improve the care of emergency
      department (ED) patients. At the request of the Council of Emergency Medicine
      Residency Directors (CORD), leaders in the field of emergency medicine (EM) US
      met to delineate in consensus fashion the model "US curriculum" for EM residency
      training programs. The goal of this article is to provide a framework for
      providing US education to EM residents. These guidelines should serve as a
      foundation for the growth of resident education in EM US. The intent of these
      guidelines is to provide minimum education standards for all EM residency
      programs to refer to when establishing an EUS training program. The document
      focuses on US curriculum, US education, and competency assessment. The use of US
      in the management of critically ill patients will improve patient care and thus
      should be viewed as a required skill set for all future graduating EM residents.
      The authors consider EUS skills critical to the development of an emergency
      physician, and a minimum skill set should be mandatory for all graduating EM
      residents. The US education provided to EM residents should be structured to
      allow residents to incorporate US into daily clinical practice. Image acquisition
      and interpretation alone are insufficient. The ability to integrate findings with
      patient care and apply them in a busy clinical environment should be stressed.

PMID- 20053208
TI  - The MERC at CORD Scholars Program in medical education research: a novel faculty
      development opportunity for emergency physicians.
AB  - Medical educators are increasingly charged with the development of outcomes-based
      "best practices" in medical student and resident education and patient care. To
      fulfill this mission, a cadre of well-trained, experienced medical education
      researchers is required. The experienced medical educator is in a prime position
      to fill this need but often lacks the training needed to successfully contribute
      to such a goal. Towards this end, the Association of American Medical Colleges
      (AAMC) Group on Educational Affairs developed a series of content-based workshops
      that have resulted in Medical Education Research Certification (MERC), promoting
      skills development and a better understanding of research by educators.
      Subsequently, the Council of Emergency Medicine Residency Directors (CORD)
      partnered with the AAMC to take MERC a step further, in the MERC at CORD Scholars
      Program (MCSP). This venture integrates a novel, mentored, specialty-specific
      research project with the traditional MERC workshops. Collaborative groups, based
      on a common area of interest, each develop a multi-institutional project by
      exploring and applying the concepts learned through the MERC workshops.
      Participants in the inaugural MCSP have completed three MERC workshops and
      initiated a project. Upon program completion, each will have completed MERC
      certification (six workshops) and gained experience as a contributing author on a
      mentored education research project. Not only does this program serve as a multi
      dimensional faculty development opportunity, it is also intended to act as a
      catalyst in developing a network of education scholars and infrastructure for
      educational research within the specialty of emergency medicine.

PMID- 20053210
TI  - A four-year perspective of Society for Academic Emergency Medicine tests: an
      online testing tool for medical students.
AB  - Nationwide survey findings that most U.S. emergency medicine clerkship directors
      were interested in participating in a methodologically rigorous student testing
      program prompted the development of the Society for Academic Emergency Medicine
      (SAEM) Medical Student Online Testing Service (SAEM Tests). This article
      describes the development of SAEM Tests and details usage and progress since the
      on-line release in June 2005. Specifically, we review the construction of SAEM
      Tests and present validity and difficulty statistics obtained at the first
      analysis of test performance 6 months after its release and again 12 months later
      after revisions aimed at enhancing test performance. We then review the current
      status of SAEM Tests and summarize future goals and directions.

PMID- 20053211
TI  - Evaluation of a web-based asynchronous pediatric emergency medicine learning tool
      for residents and medical students.
AB  - OBJECTIVES: To examine the effectiveness of an asynchronous learning tool
      consisting of web-based lectures for trainees covering major topics pertinent to
      pediatric emergency medicine (PEM) and to assess resident and student evaluation
      of this mode of education. METHODS: PEM faculty and fellows created a 21-lecture,
      web-based curriculum. These 20-minute online lectures used Microsoft PowerPoint
      with the voice-over feature. A 75-question test was created to assess the
      effectiveness of the web-based learning model, administered online before and
      after the rotation in the pediatric emergency department (PED). All fourth-year
      medical students and residents (across all specialties) rotating through the PED
      were required to complete 10 of the 21 lectures during their 1-month rotation.
      The main outcome variable was difference in score between pre- and post-rotation
      tests of participants who viewed no lectures and those who viewed at least one
      lecture. Evaluation of the program was assessed by anonymous survey using 5-point
      discrete visual analog scales. Responses of 4 or 5 were considered positive for
      analysis. RESULTS: One hundred eleven residents and fourth-year medical students
      participated in the program. An initial 32 completed testing before
      implementation of the on-line lectures (March 2007-August 2007), and another five
      did not complete the on-line lectures after implementation (September 2007
      February 2008). Seventy-one completed testing and on-line lectures, and all but
      three completed at least 10 on-line lectures during their rotation. Fourteen of
      111 trainees did not complete the pre- or post-test (including two who viewed the
      lectures). The mean change in score was a 1% improvement from pre-test to post
      test for trainees who viewed no lectures and a 6.2% improvement for those who
      viewed the lectures (mean difference = 5.2%, 95% confidence interval = 2.5% to
      7.9%). In the linear regression model, the estimate of the coefficient was 0.43
      (p < 0.001), meaning that, for each lecture viewed, post-test score rose by
      0.43%. Sixty-nine of 75 test items (92%) had a point biserial correlation greater
      than 0.15. Thirty of the 72 trainees who completed the online lectures and
      testing (42%) returned surveys. All were comfortable using the Internet, and 87%
      (26/30) found the web-site easy to use. All felt that their educational goals
      were met, and 100% felt that the format would be useful in other areas of
      education. CONCLUSIONS: Although not a replacement for traditional bedside
      teaching, the use of web-based lectures as an asynchronous learning tool has a
      positive effect on medical knowledge test scores. Trainees were able to view
      online lectures on their own schedules, in the location of their choice. This is
      helpful in a field with shift work, in which trainees rarely work together,
      making it difficult to synchronously provide lectures to all trainees.

PMID- 20053212
TI  - Real-time inter-rater reliability of the Council of Emergency Medicine residency
      directors standardized direct observation assessment tool.
AB  - OBJECTIVES: Developed by the Council of Emergency Medicine Residency Directors
      (CORD), the standardized direct observation assessment tool (SDOT) is an
      evaluation instrument used to assess residents' clinical skills in the emergency
      department (ED). In a previous study examining the inter-rater agreement of the
      tool, faculty scored simulated resident-patient encounters. The objective of the
      present study was to evaluate the inter-rater agreement of the SDOT in real-time
      evaluations of residents in the ED. METHODS: This was a multi-center,
      prospective, observational study in which faculty raters were paired to
      simultaneously observe and independently evaluate a resident's clinical
      performance using the SDOT. Data collected from eight emergency medicine (EM)
      residency programs produced 99 unique resident-patient encounters and reported on
      26 individual behaviors related to specific core competencies, global evaluation
      scores for each core competency, and an overall clinical competency score. Inter
      rater agreement was assessed using percentage agreement analyses with three
      constructs: exact agreement, liberal agreement, and binary (pass/fail) agreement.
      RESULTS: Inter-rater agreement between faculty raters varied according to
      category of measure used. Exact agreement ranged from poor to good, depending on
      the measure: the overall competency score (good), the competency score for each
      of the six core competencies (poor to good), and the individual item scores (fair
      to very good). Liberal agreement and binary agreement were excellent for the
      overall competency score and the competency score for each of the six core
      competencies and very good to excellent for the individual item scores.
      CONCLUSIONS: The SDOT demonstrated excellent inter-rater agreement when analyzed
      with liberal agreement and when dichotomized as a pass/fail measure and fair to
      good agreement for most measures with exact agreement. The SDOT can be useful and
      reliable when evaluating residents' clinical skills in the ED, particularly as it
      relates to marginal performance.

PMID- 20053213
TI  - Gaps in procedural experience and competency in medical school graduates.
AB  - OBJECTIVES: The goal of undergraduate medical education is to prepare medical
      students for residency training. Active learning approaches remain important
      elements of the curriculum. Active learning of technical procedures in medical
      schools is particularly important, because residency training time is
      increasingly at a premium because of changes in the Accreditation Council for
      Graduate Medical Education duty hour rules. Better preparation in medical school
      could result in higher levels of confidence in conducting procedures earlier in
      graduate medical education training. The hypothesis of this study was that more
      procedural training opportunities in medical school are associated with higher
      first-year resident self-reported competency with common medical procedures at
      the beginning of residency training. METHODS: A survey was developed to assess
      self-reported experience and competency with common medical procedures. The
      survey was administered to incoming first-year residents at three U.S. training
      sites. Data regarding experience, competency, and methods of medical school
      procedure training were collected. Overall satisfaction and confidence with
      procedural education were also assessed. RESULTS: There were 256 respondents to
      the procedures survey. Forty-four percent self-reported that they were marginally
      or not adequately prepared to perform common procedures. Incoming first-year
      residents reported the most procedural experience with suturing, Foley catheter
      placement, venipuncture, and vaginal delivery. The least experience was reported
      with thoracentesis, central venous access, and splinting. Most first-year
      residents had not provided basic life support, and more than one-third had not
      performed cardiopulmonary resuscitation (CPR). Participation in a targeted
      procedures course during medical school and increasing the number of procedures
      performed as a medical student were significantly associated with self-assessed
      competency at the beginning of residency training. CONCLUSIONS: Recent medical
      school graduates report lack of self-confidence in their ability to perform
      common procedures upon entering residency training. Implementation of a medical
      school procedure course to increase exposure to procedures may address this
      challenge.

PMID- 20053214
TI  - Conference attendance does not correlate with emergency medicine residency in
      training examination scores.
AB  - OBJECTIVES: The residency review committee for emergency medicine (EM) requires
      residents to have greater than 70% attendance of educational conferences during
      residency training, but it is unknown whether attendance improves clinical
      competence or scores on the American Board of Emergency Medicine (ABEM) in
      training examination (ITE). This study examined the relationship between
      conference attendance and ITE scores. The hypothesis was that greater attendance
      would correlate to a higher examination score. METHODS: This was a multi-center
      retrospective cohort study using conference attendance data and examination
      results from residents in four large county EM residency training programs.
      Longitudinal multi-level models, adjusting for training site, U.S. Medical
      Licensing Examination (USMLE) Step 1 score, and sex were used to explore the
      relationship between conference attendance and in-training examination scores
      according to year of training. Each year of training was studied, as well as the
      overall effect of mean attendance as it related to examination score. RESULTS:
      Four training sites reported data on 405 residents during 2002 to 2008; 386
      residents had sufficient data to analyze. In the multi-level longitudinal models,
      attendance at conference was not a significant predictor of in-training
      percentile score (coefficient = 0.005, 95% confidence interval [CI] = -0.053 to
      0.063, p = 0.87). Score on the USMLE Step 1 examination was a strong predictor of
      ITE score (coefficient = 0.186, 95% CI = 0.155 to 0.217; p < 0.001), as was
      female sex (coefficient = 2.117, 95% CI = 0.987 to 3.25; p < 0.001). CONCLUSIONS:
      Greater conference attendance does not correlate with performance on an
      individual's ITE scores. Conference attendance may represent an important part of
      EM residency training but perhaps not of ITE performance.

PMID- 20053215
TI  - Emergency medicine residency applicant views on the interview day process.
AB  - OBJECTIVES: Emergency medicine (EM) residency programs spend significant time and
      money offering an interview day experience for their applicants. The day may
      include a range of activities, although which are most important from the
      applicants' point of view are not known. METHODS: An anonymous web-based survey
      was sent to all applicants to an EM residency program from the 2006/07 cycle. The
      study assessed factors about the interview day that were most helpful to
      applicants in assessing goodness of fit and preparing their rank list of
      programs. RESULTS: When considering whether a program was a good fit for them,
      the respondents chose (from most to least important) how happy the residents
      seem, faculty-resident relationships, how well the residents work together,
      resident and faculty values match my own, the residents spend time together
      outside of the residency, and the residents share my outside interests.
      Applicants most value assessing program "personality," informal off-campus
      gatherings with residents, and interviewing with the program director as ways to
      decide where a program will reside on their rank list. Touring off-campus
      emergency departments and off-service facilities received the lowest rating
      averages. CONCLUSIONS: Residency programs have the opportunity to control two of
      the three most important ways in which applicants use the interview day to assess
      programs by offering off-campus gatherings with residents and ensuring that every
      candidate interviews with the program director. Residency programs may use this
      knowledge to optimize interview day resources.

PMID- 20053216
TI  - Using screen-based simulation to improve performance during pediatric
      resuscitation.
AB  - OBJECTIVES: To assess the ability of a screen-based simulation-training program
      to improve emergency medicine and pediatric resident performance in critical
      pediatric resuscitation knowledge, confidence, and skills. METHODS: A pre-post,
      interventional design was used. Three measures of performance were created and
      assessed before and after intervention: a written pre-course knowledge
      examination, a self-efficacy confidence score, and a skills-based high-fidelity
      simulation code scenario. For the high-fidelity skills assessment, independent
      physician raters recorded and reviewed subject performance. The intervention
      consisted of eight screen-based pediatric resuscitation scenarios that subjects
      had 4 weeks to complete. Upon completion of the scenarios, all three measures
      were repeated. For the confidence assessment, summary pre- and post-test summary
      confidence scores were compared using a t-test, and for the skills assessment,
      pre-scores were compared with post-test measures for each individual using
      McNemar's chi-square test for paired samples. RESULTS: Twenty-six of 35 (71.3%)
      enrolled subjects completed the institutional review board-approved study.
      Increases were observed in written test scores, confidence, and some critical
      interventions in high-fidelity simulation. The mean improvement in cumulative
      confidence scores for all residents was 10.1 (SD +/-4.9; range 0-19; p < 0.001),
      with no resident feeling less confident after the intervention. Although overall
      performance in simulated codes did not change significantly, with average scores
      of 6.65 (+/-1.76) to 7.04 (+/-1.37) out of 9 possible points (p = 0.58),
      improvement was seen in the administering of appropriate amounts of IV fluids (59
      89%, p = 0.03). CONCLUSIONS: In this study, improvements in resident knowledge,
      confidence, and performance of certain skills in simulated pediatric cardiac
      arrest scenarios suggest that screen-based simulations may be an effective way to
      enhance resuscitation skills of pediatric providers. These results should be
      confirmed using a randomized design with an appropriate control group.

PMID- 20053217
TI  - Attending and resident satisfaction with feedback in the emergency department.
AB  - OBJECTIVES: Effective feedback is critical to medical education. Little is known
      about emergency medicine (EM) attending and resident physician perceptions of
      feedback. The focus of this study was to examine perceptions of the educational
      feedback that attending physicians give to residents in the clinical environment
      of the emergency department (ED). The authors compared attending and resident
      satisfaction with real-time feedback and hypothesized that the two groups would
      report different overall satisfaction with the feedback they currently give and
      receive in the ED. METHODS: This observational study surveyed attending and
      resident physicians at 17 EM residency programs through web-based surveys. The
      primary outcome was overall satisfaction with feedback in the ED, ranked on a 10
      point scale. Additional survey items addressed specific aspects of feedback.
      Responses were compared using a linear generalized estimating equation (GEE)
      model for overall satisfaction, a logistic GEE model for dichotomized responses,
      and an ordinal logistic GEE model for ordinal responses. RESULTS: Three hundred
      seventy-three of 525 (71%) attending physicians and 356 of 596 (60%) residents
      completed the survey. Attending physicians were more satisfied with overall
      feedback (mean score 5.97 vs. 5.29, p < 0.001) and with timeliness of feedback
      (odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.23 to 2.00; p < 0.001)
      than residents. Attending physicians were also more likely to rate the quality of
      feedback as very good or excellent for positive feedback, constructive feedback,
      feedback on procedures, documentation, management of ED flow, and evidence-based
      decision-making. Attending physicians reported time constraints as the top
      obstacle to giving feedback and were more likely than residents to report that
      feedback is usually attending initiated (OR = 7.09, 95% CI = 3.53 to 14.31; p <
      0.001). CONCLUSIONS: Attending physician satisfaction with the quality,
      timeliness, and frequency of feedback given is higher than resident physician
      satisfaction with feedback received. Attending and resident physicians have
      differing perceptions of who initiates feedback and how long it takes to provide
      effective feedback. Knowledge of these differences in perceptions about feedback
      may be used to direct future educational efforts to improve feedback in the ED.

PMID- 20053218
TI  - Public health in the emergency department: Academic Emergency Medicine consensus
      conference executive summary.

PMID- 20053219
TI  - Public health and emergency medicine.

PMID- 20053220
TI  - Idealized models or incremental program evaluation: translating emergency
      department HIV testing into practice.

PMID- 20053221
TI  - Historical parallel evolution of injury prevention and control science and
      emergency medicine.

PMID- 20053222
TI  - The clinical impact of health behaviors on emergency department visits.
AB  - Modifiable health behaviors are an important cause of visits to emergency
      departments (EDs). Substance use, unsafe sexual behavior, interpersonal violence,
      unintentional injury, and other risky behaviors account for a large proportion of
      ED volume, as well as up to 40% of all deaths in the United States. While
      emergency physicians commonly treat the illnesses and injuries caused by these
      behaviors, additional opportunities exist to screen, intervene, refer, and
      initiate treatment for patients with these health risks. This article reviews the
      epidemiology and clinical impact of risky health behaviors on ED visits and
      suggests strategies for creating a research agenda in these areas.

PMID- 20053223
TI  - Emergency medicine and public health: stopping emergencies before the 9-1-1 call.

PMID- 20053224
TI  - Emergency medicine public health research funded by federal agencies: progress
      and priorities.
AB  - The emergency department (ED) visit provides an opportunity to impact the health
      of the public throughout the entire spectrum of care, from prevention to
      treatment. As the federal government has a vested interest in funding research
      and providing programmatic opportunities that promote the health of the public,
      emergency medicine (EM) is prime to develop a research agenda to advance the
      field. EM researchers need to be aware of federal funding opportunities, which
      entails an understanding of the organizational structure of the federal agencies
      that fund medical research, and the rules and regulations governing applications
      for grants. Additionally, there are numerous funding streams outside of the
      National Institutes of Health (NIH; the primary federal health research agency).
      EM researchers should seek funding from agencies according to each agency's
      mission and aims. Finally, while funds from the Department of Health and Human
      Services (HHS) are an important source of support for EM research, we need to
      look beyond traditional sources and appeal to other agencies with a vested
      interest in promoting public health in EDs. EM requires a broad skill set from a
      multitude of medical disciplines, and conducting research in the field will
      require looking for funding opportunities in a variety of traditional and not so
      traditional places within and without the federal government. The following is
      the discussion of a moderated session at the 2009 Academic Emergency Medicine
      consensus conference that included panel discussants from the National Institutes
      of Mental Health, Drug Abuse, and Alcoholism and Alcohol Abuse and the Centers
      for Disease Control and Prevention (CDC). Further information is also provided to
      discuss those agencies and centers not represented.

PMID- 20053225
TI  - SBIRT in emergency care settings: are we ready to take it to scale?
AB  - This article summarizes a panel discussion on "SBIRT in the emergency care
      setting: are we ready to take it to scale?" Dr. Edward Bernstein commented on the
      historical developments of emergency department (ED) screening, brief
      intervention (BI), and referral to treatment (SBIRT) research, practice, and
      knowledge translation. Dr. Jack Stein addressed SBIRT grant program progress to
      date, the reimbursement stream, SBIRT lessons learned, and unanswered questions.
      Dr. Richard Saitz reviewed the limitations of the evidence for alcohol and drug
      ED screening and BI and cautioned on the danger of proceeding to practice and
      broad dissemination without evidenced based on randomized controlled trials with
      sufficient sample size and clinically important outcomes.

PMID- 20053226
TI  - Alcohol, tobacco, and other drugs: future directions for screening and
      intervention in the emergency department.
AB  - This article is a product of a breakout session on injury prevention from the
      2009 Academic Emergency Medicine consensus conference on "Public Health in the
      ED: Screening, Surveillance, and Intervention." The emergency department (ED) is
      an important entry portal into the medical care system. Given the epidemiology of
      substance use among ED patients, the delivery of effective brief interventions
      (BIs) for alcohol, drug, and tobacco use in the ED has the potential to have a
      large public health impact. To date, the results of randomized controlled trials
      of interventional studies in the ED setting for substance use have been mixed in
      regard to alcohol and understudied in the area of tobacco and other drugs. As a
      result, there are more questions remaining than answered. The work group
      developed the following research recommendations that are essential for the field
      of screening and BI for alcohol, tobacco, and other drugs in the ED. 1) Screening
      -develop and validate brief and practical screening instruments for ED patients
      and determine the optimal method for the administration of screening instruments.
      2) Key components and delivery methods for intervention--conduct research on the
      effectiveness of screening, brief intervention, and referral to treatment (SBIRT)
      in the ED on outcomes (e.g., consumption, associated risk behaviors, and medical
      psychosocial consequences) including minimum dose needed, key components, optimal
      delivery method, interventions focused on multiple risk behaviors and tailored
      based on assessment, and strategies for addressing polysubstance use. 3)
      Effectiveness among patient subgroups--conduct research to determine which
      patients are most likely to benefit from a BI for substance use, including
      research on moderators and mediators of intervention effectiveness, and examine
      special populations using culturally and developmentally appropriate
      interventions. 4) Referral strategies--a) promote prospective effectiveness
      trials to test best strategies to facilitate referrals and access from the ED to
      preventive services, community resources, and substance abuse and mental health
      treatment; b) examine impact of available community services; c) examine the role
      of stigma of referral and follow-up; and d) examine alternatives to specialized
      treatment referral. 5) Translation--conduct translational and cost-effectiveness
      research of proven efficacious interventions, with attention to fidelity, to move
      ED SBIRT from research to practice.

PMID- 20053227
TI  - Violence prevention in the emergency department: future research priorities.
AB  - The 2009 Academic Emergency Medicine Consensus Conference working group session
      participants developed recommendations and research questions for violence
      prevention in the emergency department (ED). A writing group devised a working
      draft prior to the meeting and presented this to the breakout session at the
      consensus conference for input and approval. The recommendations include: 1)
      promote and facilitate the collection of standardized information related to
      violence victimization and perpetration in ED settings; 2) develop and validate
      brief practical screening instruments that can identify those at risk for
      perpetration of violence toward others or toward self; 3) develop and validate
      brief practical screening instruments that can identify victims at risk for
      violent reinjury and mental health sequelae; and 4) conduct efficacy,
      translational, and dissemination research on interventions for violence
      prevention. The work group emphasized the critical need and role of ED-based
      research to impact surveillance and prevention of future violence-related injury.

PMID- 20053228
TI  - Research priorities for human immunodeficiency virus and sexually transmitted
      infections surveillance, screening, and intervention in emergency departments:
      consensus-based recommendations.
AB  - This article describes the results of the human immunodeficiency virus (HIV) and
      sexually transmitted infections (STI) prevention in the emergency department (ED)
      component of the 2009 Academic Emergency Medicine Consensus Conference entitled
      "Public Health in the ED: Surveillance, Screening, and Intervention." The
      objectives were to use experts to define knowledge gaps and priority research
      questions related to the performance of HIV and STI surveillance, screening, and
      intervention in the ED. A four-step nominal group technique was applied using
      national and international experts in HIV and STI prevention. Using electronic
      mail, an in-person meeting, and a Web-based survey, specific knowledge gaps and
      research questions were identified and prioritized. Through two rounds of
      nomination and refinement, followed by two rounds of election, consensus was
      achieved for 11 knowledge gaps and 14 research questions related to HIV and STI
      prevention in EDs. The overarching themes of the research priority questions were
      related to effectiveness, sustainability, and integration. While the knowledge
      gaps appear disparate from one another, they are related to the research priority
      questions identified. Using a consensus approach, we developed a set of
      priorities for future research related to HIV and STI prevention in the ED. These
      priorities have the potential to improve future clinical and health services
      research and extramural funding in this important public health sector.

PMID- 20053229
TI  - Research using emergency department-related data sets: current status and future
      directions.
AB  - The 2009 Academic Emergency Medicine consensus conference focused on "Public
      Health in the ED: Surveillance, Screening and Intervention." One conference
      breakout session discussed the significant research value of health-related data
      sets. This article represents the proceedings from that session, primarily
      focusing on emergency department (ED)-related data sets and includes examples of
      the use of a data set based on ED visits for research purposes. It discusses
      types of ED-related data sets available, highlights barriers to research use of
      ED-related data sets, and notes limitations of these data sets. The paper
      highlights future directions and challenges to using these important sources of
      data for research, including identification of five main needs related to
      enhancing the use of ED-related data sets. These are 1) electronic linkage of
      initial and follow-up ED visits and linkage of information about ED visits to
      other outcomes, including costs of care, while maintaining de-identification of
      the data; 2) timely data access with minimal barriers; 3) complete data
      collection for clinically relevant and/or historical data elements, such as the
      external cause-of-injury code; 4) easy access to data that can be parsed into
      smaller jurisdictions (such as states) for policy and/or research purposes, while
      maintaining confidentiality; and 5) linkages between health survey data and
      health claims data. ED-related data sets contain much data collected directly
      from health care facilities, individual patient records, and multiple other
      sources that have significant potential impact for studying and improving the
      health of individuals and the population.

PMID- 20053230
TI  - Mental health and emergency medicine: a research agenda.
AB  - The burden of mental illness is profound and growing. Coupled with large gaps in
      extant psychiatric services, this mental health burden has often forced emergency
      departments (EDs) to become the de facto primary and acute care provider of
      mental health care in the United States. An expanded emergency medical and mental
      health research agenda is required to meet the need for improved education,
      screening, surveillance, and ED-initiated interventions for mental health
      problems. As an increasing fraction of undiagnosed and untreated psychiatric
      patients passes through the revolving doors of U.S. EDs, the opportunities for
      improving the art and science of acute mental health care have never been
      greater. These opportunities span macroepidemiologic surveillance research to
      intervention studies with individual patients. Feasible screening, intervention,
      and referral programs for mental health patients presenting to general EDs are
      needed. Additional research is needed to improve the quality of care, including
      the attitudes, abilities, interests, and virtues of ED providers. Research that
      optimizes provider education and training can help academic settings validate
      psychosocial issues as core components and responsibilities of emergency
      medicine. Transdisciplinary research with federal partners and investigators in
      neuropsychiatry and related fields can improve the mechanistic understanding of
      acute mental health problems. To have lasting impact, however, advances in ED
      mental health care must be translated into real-world policies and sustainable
      program enhancements to assure the uptake of best practices for ED screening,
      treatment, and management of mental disorders and psychosocial problems.

PMID- 20053231
TI  - Conceptual models of health behavior: research in the emergency care settings.
AB  - This article provides recommendations for incorporating conceptual models of
      health behavior change into research conducted in emergency care settings. The
      authors drafted a set of preliminary recommendations, which were reviewed and
      discussed by a panel of experienced investigators attending the 2009 Academic
      Emergency Medicine consensus conference. The original recommendations were
      expanded and refined based on their input. This article reports the final
      recommendations. Three recommendations were made: 1) research conducted in
      emergency care settings that focuses on health behaviors should be grounded in
      formal conceptual models, 2) investigators should clearly operationalize their
      outcomes of interest, and 3) expected relations between theoretical constructs
      and outcomes should be made explicit prior to initiating a study. A priori
      hypothesis generation grounded in conceptual models of health behavior, followed
      by empirical validation of these hypotheses, is needed to improve preventive and
      public health-related interventions in emergency care settings.

PMID- 20053233
TI  - Public health in the emergency department: overcoming barriers to implementation
      and dissemination.
AB  - This article is the outcome of a consensus building workshop entitled,
      "Overcoming Barriers to Implementation and Dissemination" convened at the 2009
      Academic Emergency Medicine Consensus Conference, ''Public Health in the ED:
      Surveillance, Screening, and Intervention." The participants were asked to
      address potential methods for overcoming barriers to the dissemination and
      implementation in the emergency department (ED) of evidenced-based practices to
      improve public health. The panel discussed three broad areas of interest
      including methods for disseminating evidence-based practices, barriers
      encountered during the process of implementation, and the importance of
      involvement in activities outside the ED including engagement in policy
      development and improvement. Four recommendations were discussed in detail and
      consensus was reached. The recommendations included 1) researchers and advocates
      should disseminate findings through multiple forums beyond peer-reviewed
      publications when an ED-based public health intervention has enough evidence to
      support integration into the routine practice of emergency care; 2) local
      barriers to implementation of public health interventions should be recognized
      and well understood from multiple perspectives prior to implementation; 3)
      innovation must be put into place and adapted based on local institutional
      context and culture as barriers and the best methods for overcoming them will
      vary across institutions; and 4) use of legislation, regulation, and incentives
      outside of the ED should support and strengthen ED-based interventions. For each
      area of interest, research dimensions to extend the current understanding of
      methods for effectively and efficiently implementing evidence-based public health
      interventions in the ED were discussed and consensus was achieved.

PMID- 20053232
TI  - Study designs and evaluation models for emergency department public health
      research.
AB  - Abstract Public health research requires sound design and thoughtful
      consideration of potential biases that may influence the validity of results. It
      also requires careful implementation of protocols and procedures that are likely
      to translate from the research environment to actual clinical practice. This
      article is the product of a breakout session from the 2009 Academic Emergency
      Medicine consensus conference entitled "Public Health in the ED: Screening,
      Surveillance, and Intervention" and serves to describe in detail aspects of
      performing emergency department (ED)-based public health research, while serving
      as a resource for current and future researchers. In doing so, the authors
      describe methodologic features of study design, participant selection and
      retention, and measurements and analyses pertinent to public health research. In
      addition, a number of recommendations related to research methods and future
      investigations related to public health work in the ED are provided. Public
      health investigators are poised to make substantial contributions to this
      important area of research, but this will only be accomplished by employing sound
      research methodology in the context of rigorous program evaluation.

PMID- 20053234
TI  - Public health in the emergency department: surveillance, screening, and
      intervention--funding and sustainability.
AB  - This article summarizes the work and discussions of the funding and
      sustainability work group at the 2009 Academic Emergency Medicine consensus
      conference "Public Health in the ED: Surveillance, Screening, and Intervention."
      The funding and sustainability session participants were asked to address the
      following overarching question: "What are the opportunities and what is needed to
      encourage academic emergency medicine (EM) to take advantage of the opportunities
      for funding available for public health research initiatives and build stronger
      academic programs focusing on public health within EM?" Prior to the session,
      members of the group reviewed research funding for EM in public health, as well
      as the priorities of federal agencies and foundations. Recommendations for
      actions by EM summarize the findings of workshop.

PMID- 20053235
TI  - Effectiveness of increasing emergency department patients' self-perceived risk
      for being human immunodeficiency virus (HIV) infected through audio computer self
      interview-based feedback about reported HIV risk behaviors.
AB  - OBJECTIVES: Prior research has demonstrated that emergency department (ED)
      patient acceptance of human immunodeficiency virus (HIV) screening is partially
      dependent on patients' self-perceived risk of infection. The primary objective of
      this study was to determine the effectiveness of audio computer-assisted self
      interview (ACASI)-based feedback. The intervention aimed to increase patient's
      self-perceived risk of being HIV infected by providing immediate feedback on
      their risk behaviors. METHODS: This 1-year, randomized, controlled trial at a
      U.S. ED enrolled a random sample of 18- to 64-year-old subcritically ill or
      injured adult patients who were not known to be HIV infected. All participants
      completed an anonymous, ACASI-based questionnaire about their HIV risk behaviors
      related to injection drug use and sex, as well as their self-perceived risk for
      being HIV infected. Participants were randomly assigned to one of two study
      groups: an intervention group in which participants received immediate ACASI
      based feedback in response to each of their reported risk behaviors or a no
      intervention group without feedback. Participants were asked to indicate their
      level of HIV risk on a five-point scale before and after they answered the
      questions. Change in level of self-perceived HIV risk was calculated and compared
      by study group using Pearson's chi-square test. An HIV risk behavior score that
      summarized reported HIV risk behavior was devised. Because HIV risk behaviors
      differ by sex, scores were calculated separately for each sex. Linear regression
      models that adjusted for study group and same subject covariance were employed to
      determine if higher HIV risk behavior scores were associated with an increase in
      self-perceived HIV risk. RESULTS: Of the 566 trial participants, the median age
      was 29 years (interquartile range [IQR] = 22-43 years), 62.2% were females, and
      66.9% had been tested previously for HIV. After answering the reported HIV risk
      behavior questions, 12.6% of participants had an increase, 79.9% had no change,
      and 7.5% had a decrease in self-perceived HIV risk. Of the 46.6% of participants
      who initially indicated that they were not at risk for HIV, 11.4% had an increase
      in self-perceived HIV risk after answering the reported HIV risk behavior
      questions. Change in self-perceived HIV risk did not differ by study group (p =
      0.77). There were no differences in reported HIV risk scores between the
      intervention and no-intervention groups for females (p = 0.78) or males (p =
      0.86). In the linear regression models, a greater increase in self-perceived HIV
      risk was associated with higher reported HIV risk behavior scores for females
      (beta = 0.59, 95% confidence interval [CI] = 0.15, 1.04) but not for males (beta
      = 1.00, 95% CI = -0.13 to 2.14). CONCLUSIONS: Some ED patients can be moved,
      although modestly, to recognize their risk for being HIV infected by asking about
      their HIV risk behaviors. However, ACASI-based feedback messages about HIV risk
      behaviors do not increase subjects' self-perceived HIV risk. Female ED patients
      appear to increase their self-perceived HIV risk more than males when queried
      about their HIV risk behaviors.

PMID- 20053236
TI  - Acceptance of rapid HIV screening in a southeastern emergency department.
AB  - OBJECTIVES: The objective was to assess the acceptance of an emergency department
      (ED) human immunodeficiency virus (HIV) screening program based on the Centers
      for Disease Control and Prevention (CDC) recommendations for routine HIV
      screening in health care settings. METHODS: Rapid HIV screening was offered on an
      opt-out basis to patients aged 13 to 64 years presenting to the ED by trained HIV
      counselors. Patients were excluded if they had a history of HIV, were physically
      or mentally incapacitated, did not understand their right to opt-out, or did not
      speak English or Spanish. Statistical analyses, including logistic regression,
      were performed to assess the associations between the demographics of patients
      offered testing and their test acceptance or refusal. RESULTS: From March 2008 to
      January 2009, a total of 5,080 (91%) of the 5,585 patients offered the HIV test
      accepted, and 506 (9%) refused. White and married patients were less likely to
      accept testing than those who were African American and unmarried (p < 0.001).
      Adult patients were almost twice as likely to accept testing as pediatric
      patients (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.50 to 2.53).
      As age increased among pediatric patients, testing refusal decreased (OR = 0.71;
      95% CI = 0.59 to 0.85), and as age increased among adult patients, testing
      refusal increased (OR = 1.17; 95% CI = 1.12 to 1.22). Two percent of persons
      accepting the test were considered high risk. Males were more likely to report
      high-risk behavior than females (OR = 1.83; 95% CI = 1.23 to 2.72). CONCLUSIONS:
      The opt-out approach results in high acceptance of routine HIV screening.
      Widespread adoption of the CDC's recommendations, although feasible, will require
      significant increases in resources.

PMID- 20053237
TI  - Emergency medicine resident attitudes and perceptions of HIV testing before and
      after a focused training program and testing implementation.
AB  - OBJECTIVES: The objectives were to determine attitudes and perceptions (A&P) of
      emergency medicine (EM) residents toward emergency department (ED) routine
      provider-driven rapid HIV testing services and the impact of both a focused
      training program (FTP) and implementation of HIV testing on A&P. METHODS: A three
      phase, consecutive, anonymous, identity-unlinked survey was conducted pre-FTP,
      post-FTP, and 6 months postimplementation. The survey was designed to assess
      residents' A&P using a five-point Likert scale. A preimplementation FTP provided
      both the rationale for the HIV testing program and the planned operational
      details of the intervention. The HIV testing program used only indigenous ED
      staff to deliver HIV testing as part of standard-of-care in an academic ED. The
      impact of the FTP and implementation on A&P were analyzed by multivariate
      regression analysis using generalized estimating equations to control for
      repeated measurements in the same individuals. A "favorable" A&P was
      operationally defined as a mean score of >3.5, "neutral" as mean score of 2.5 to
      3.5, and "unfavorable" as mean score of <2.5. RESULTS: Thirty of 36 residents
      (83.3%) participated in all three phases. Areas of favorable A&P found in phase I
      and sustained through phases II and III included "ED serving as a testing venue"
      (score range = 3.7-4.1) and "emergency medicine physicians offering the test"
      (score range = 3.9-4.1). Areas of unfavorable and neutral A&P identified in phase
      I were all operational barriers and included required paperwork (score = 3.2),
      inadequate staff support (score = 2.2), counseling and referral requirements
      (score range = 2.2-3.1), and time requirements (score = 2.9). Following the FTP,
      significant increases in favorable A&P were observed with regard to impact of the
      intervention on modification of patient risk behaviors, decrease in rates of HIV
      transmission, availability of support staff, and self-confidence in counseling
      and referral (p < 0.05). At 6 months postimplementation, all A&P except for time
      requirements and lack of support staff scored favorably or neutral. During the
      study period, 388 patients were consented for and received HIV testing; six
      (1.5%) were newly confirmed HIV positive. CONCLUSIONS: Emergency medicine
      residents conceptually supported HIV testing services. Most A&P were favorably
      influenced by both the FTP and the implementation. All areas of negative A&P
      involved operational requirements, which may have influenced the low overall
      uptake of HIV testing during the study period.

PMID- 20053238
TI  - Screening and brief intervention to reduce marijuana use among youth and young
      adults in a pediatric emergency department.
AB  - OBJECTIVES: Marijuana was involved in 209,563 emergency department (ED) visits in
      2006, according to the Drug Abuse Warning Network. Although screening and brief
      intervention (SBI) has been effective in changing drinking among ED patients in a
      number of studies, tests of marijuana SBI in a pediatric emergency department
      (PED) have not yet been reported. The aim of this pilot study was to test whether
      SBI is effective in reducing marijuana consumption among youth and young adults
      presenting to a PED with a diverse range of clinical entities. METHODS: A three
      group randomized controlled preliminary trial was structured to test 1)
      differences between Intervention (Int) and standard Assessed Control (AC) groups
      in marijuana consumption, from baseline to 12 months, and 2) the feasibility of
      adding a Nonassessed Control (NAC) group to evaluate regression to the mean and
      assessment reactivity. Patients aged 14-21 years in an urban, academic PED were
      screened during 2006-2007, using standardized risk factor questions. Subjects
      were eligible if they used marijuana three or more times in the past 30 days, but
      were excluded for co-occurring high-risk alcohol use. Consented enrollees were
      randomized to NAC, AC, and Int groups in a two-stage process that permitted
      blinding to status during assessment and follow-up. NACs received a resource
      handout, written advice about marijuana use risks, and a 12-month follow-up
      appointment. ACs were assessed using standardized instruments and received
      resources, written advice, and 3- and 12-month follow-up appointments. The Int
      group received assessment, resources, written advice, 3- and 12-month
      appointments, a 20-minute structured conversation conducted by older peers, and a
      10-day booster telephone call. A peer educator utilized a motivational style
      interview protocol adapted for adolescents to elicit daily life context and
      future goals, provide feedback, review pros and cons of marijuana use, assess
      readiness to change, evaluate strengths and assets, negotiate a contract for
      change, and make referrals to treatment and/or other resources. Measurements
      included demographic information; 30-day self-report of marijuana use; attempts
      to quit, cut back, or change conditions of use; and risk factor questions
      repeated at follow-up. RESULTS: Among 7,804 PED patients screened, 325 were
      eligible; 210 consented and enrolled (Int, n = 68; AC, n = 71; NAC, n = 71), with
      a 12-month follow-up rate of 71%. For the primary objective, we compared Int to
      AC. At 12 months, Int participants were more likely to be abstinent for the past
      30 days than ACs (odds ratio [OR] for reported abstinence = 2.89, 95% confidence
      interval [CI] = 1.22 to 6.84, p < 0.014). The Int group had greater reduction in
      days used, baseline to 12 months, controlling for baseline (Int = -7.1 vs. AC = 
      1.8), were less likely to have been high among those who smoked (OR = 0.39, 95%
      CI = 0.17 to 0.89, p < 0.05), and were more likely to receive referrals. In a
      linear regression model controlling for baseline use, NACs smoked 4 fewer days
      per month than ACs, but consumption was not significantly different, suggesting
      no assessment reactivity effect. CONCLUSIONS: A preliminary trial of SBI promoted
      marijuana abstinence and reduced consumption among PED patients aged 14-21 years.
      A no-contact condition for the NAC group over the year after enrollment was
      insufficient to capture enrollees for follow-up across a range of baseline
      acuity.

PMID- 20053239
TI  - Tobacco screening multicomponent quality improvement network program: beyond
      education.
AB  - OBJECTIVES: Due to the addictive nature of the disease and interrelated societal
      influences on the behavior of tobacco use, repeated interventions are often
      required before people successfully stop using tobacco. Our objective was to
      implement a multicomponent clinical intervention initiative enabling health care
      providers to effectively screen for tobacco use. We also sought to describe
      changes in emergency medicine providers' documentation of cessation advice to
      tobacco users. METHODS: The intervention was conducted at three emergency
      departments (EDs) and four clinics at a community-based teaching hospital and
      health network. Health care providers with the opportunity to identify and
      counsel tobacco-using patients in ambulatory health care settings were the study
      population. The authors initiated a quality improvement initiative for tobacco
      screening that employed a multicomponent strategy to facilitate systemic changes
      that support 100% tobacco use identification, documentation, and counseling.
      Baseline, posteducation, and post-wrap-around documented screening rates were
      compared within each site across the intervention. Cumulative ED baseline,
      posteducation, and post-wrap-around rates of provider advice to tobacco users
      were compared across the intervention. Percentage of possible available gain was
      calculated in consideration of a 100% ceiling effect. Statistical analysis was
      performed using SPSS and MetStat. Descriptive statistics and Pearson's chi-square
      cell frequency were used to analyze and compare sites. Fisher's exact test was
      used to compare those tests with a chi-square cell frequency of five or less. The
      statistical tests used for pre-/postintervention percentage comparisons by site
      had power between 80% and 90%, detecting differences of 10% and 20% or more at a
      0.05 level of significance. RESULTS: Significant increases in posteducation
      screening rates for all ED sites complemented significant increases in ED post
      wrap-around intervention screening rates. Significant increases in ED provider
      documented cessation advice were also noted. CONCLUSIONS: This initiative
      successfully changed tobacco screening behavior of health care providers at all
      sites. It was particularly successful in the ED, typically an environment less
      likely to be conducive to preventive health interventions.

PMID- 20053241
TI  - Intimate partner violence: development of a brief risk assessment for the
      emergency department.
AB  - OBJECTIVES: Women assaulted by intimate partners are frequently patients in
      emergency departments (EDs). Many victims and health care providers fail to take
      into account the potential risks of repeat partner violence. The objective of
      this study was to use data from a larger study of domestic violence risk
      assessment methods to develop a brief assessment for acute care settings to
      identify victims at highest risk for suffering severe injury or potentially
      lethal assault by an intimate partner or former partner. METHODS: Victims of
      intimate partner violence (IPV) were interviewed twice between 2002 and 2004. The
      baseline interview included the 20 items of Campbell's Danger Assessment (DA;
      predictor). The follow-up interview, conducted 9 months later on average,
      assessed abuse inflicted since the baseline interview (outcome). Multiple
      logistic regression was used to identify questions on the DA most predictive of
      severe abuse and potentially lethal assaults. Female IPV victims were recruited
      from New York City family courts, Los Angeles County Sheriff's Department 9-1-1
      calls, New York City and Los Angeles shelters, and New York City hospitals; 666
      women responded to the DA at baseline, and 60% participated in follow-up
      interviews. RESULTS: Severe injuries or potentially lethal assaults were
      experienced by 14.9% of retained study participants between the baseline and
      follow-up interviews. The best brief prediction instrument has five questions. A
      positive answer to any three questions has a sensitivity of 83% (95% confidence
      interval = 70.6% to 91.4%). CONCLUSIONS: This instrument can help predict which
      victims may be at increased risk for severe injury or potentially lethal assault
      and can aid clinicians in differentiating which patients require comprehensive
      safety interventions.

PMID- 20053240
TI  - Three-month follow-up of brief computerized and therapist interventions for
      alcohol and violence among teens.
AB  - OBJECTIVES: Alcohol use and violent behaviors are well documented among
      adolescents and have enormous effects on morbidity and mortality. The authors
      hypothesized that universal computer screening of teens in an inner-city
      emergency department (ED), followed by a brief intervention (BI), would be 1)
      feasible (as measured by participation and completion of BI during the ED visit)
      and well received by teens (as measured by posttest process measures of
      intervention acceptability) and 2) effective at changing known precursors to
      behavior change such as attitudes, self-efficacy, and readiness to change alcohol
      use and violence. METHODS: Adolescent patients (ages 14-18 years) at an urban ED
      were approached to complete a computerized survey. The survey was conducted daily
      from 12 noon to 11 pm from September 2006 through November 2008. Adolescents
      reporting both alcohol use and violence in the past year were randomized to a
      control group or a 35-minute BI delivered by a computer or therapist as part of
      the SafERteens study. Validated measures were administered, including
      demographics, alcohol use, attitudes toward alcohol and violence, self-efficacy
      for alcohol and violence, readiness to change alcohol and violence, and process
      questions, including likeability of intervention. RESULTS: A total of 2,423
      adolescents were screened. Thirteen percent of those approached refused. The
      population was 45% male, 58% African American, and 6.2% Hispanic. Of those
      screened, 637 adolescents (26%) screened positive; 533 were randomized to
      participate, and 515 completed the BI prior to discharge. The BIs were well
      received by the adolescents overall; 97% of those randomized to a BI self
      reported that they found one intervention section "very helpful." At posttest,
      significant reductions in positive attitudes for alcohol use and violence and
      significant increases in self-efficacy related to alcohol/violence were found for
      both therapist and computer interventions. At 3-month follow-up there was 81%
      retention, and generalized estimating equations (GEE) analysis showed that
      participants in both interventions had significant reductions in positive
      attitudes for alcohol use (therapist p = 0.002, computer p = 0.0001) and violence
      (therapist p = 0.012, computer p = 0.007) and significant increases in self
      efficacy related to violence (therapist p = 0.0.04, computer p = 0.002); alcohol
      self-efficacy improved in the therapist BI condition only (therapist p = 0.050,
      computer p = 0.083). Readiness to change was not significantly improved.
      CONCLUSIONS: This initial evaluation of the SafERteens study shows that universal
      computerized screening and BI for multiple risk behaviors among adolescents is
      feasible, well received, and effective at altering attitudes and self-efficacy.
      Future evaluations of the SafERteens study will evaluate the interventions'
      effects on behavioral change (alcohol use and violence) over the year following
      the ED visit.

PMID- 20053242
TI  - A preliminary report of knowledge translation: lessons from taking screening and
      brief intervention techniques from the research setting into regional systems of
      care.
AB  - This article describes a limited statewide dissemination of an evidence-based
      technology, screening, brief intervention, and referral to treatment (SBIRT), and
      evaluation of the effects on emergency department (ED) systems of care, utilizing
      the knowledge translation framework of reach, effectiveness, adoption,
      implementation, and maintenance (RE-AIM), using both quantitative and qualitative
      data sources. Screening and brief intervention (SBI) can detect high-risk and
      dependent alcohol and drug use in the medical setting, provide early
      intervention, facilitate access to specialty treatment when appropriate, and
      improve quality of care. Several meta-analyses demonstrate its effectiveness in
      primary care, and the federal government has developed a well-funded campaign to
      promote physician training and adoption of SBI. In the busy environment of the
      ED, with its competing priorities, researchers have tested a collaborative
      approach that relies on peer educators, with substance abuse treatment experience
      and broad community contact, as physician extenders. The ED-SBIRT model of care
      reflects clinician staff time constraints and resource limitations and is
      designed for the high rates of prevalence and increased acuity typical of ED
      patients. This report tracks services provided during dissemination of the ED
      SBIRT extender model to seven EDs across a northeastern state, in urban,
      suburban, and rural community settings. Twelve health promotion advocates (HPAs)
      were hired, trained, and integrated into seven ED teams. Over an 18-month start
      up period, HPAs screened 15,383 patients; of those, 4,899 were positive for high
      risk or dependent drinking and/or drug use. Among the positive screens, 4,035
      (82%) received a brief intervention, and 57% of all positives were referred to
      the substance abuse treatment system and other community resources. Standardized,
      confidential interviews were conducted by two interviewers external to the
      program with 24 informants, including HPAs and their supervisors, clinicians,
      nurse managers, and ED directors across five sites. A detailed semistructured
      format was followed, and results were coded for thematic material. Barriers,
      challenges, and successes are described in the respondents' own words to convey
      their experience of this demonstration of SBIRT knowledge translation. Five of
      seven sites were sustained through the second year of the program, despite
      cutbacks in state funding. The dissemination process provided a number of
      important lessons for a large rollout. Successful implementation of the ED-SBIRT
      HPA model depends on 1) external funding for start-up; 2) local ED staff acting
      as champions to support the HPA role, resolve territorial issues, and promote a
      cultural shift in the ED treatment of drug and alcohol misuse from "treat and
      street" to prevention, based on a knowledge of the science of addiction; 3)
      sustainability planning from the beginning involving administrators, the billing
      and information technology departments, medical records coders, community service
      providers, and government agencies; and 4) creation and maintenance of a robust
      referral network to facilitate patient acceptance and access to substance abuse
      services.

PMID- 20053243
TI  - Routine screening for asymptomatic abdominal aortic aneurysm in high-risk
      patients is not recommended in emergency departments that are frequently crowded.
AB  - OBJECTIVES: The objectives were to examine the feasibility of offering abdominal
      aortic aneurysm (AAA) screening to consecutive, asymptomatic high-risk patients
      in a busy emergency department (ED) and to compare the prevalence of undetected
      AAA among ED patients to the prevalence among similarly aged men from the general
      population. METHODS: A prospective cohort study was conducted at an academic
      community ED with an annual census of 58,000 patients. Dedicated study
      coordinators attempted to approach all consecutive male ED patients >50 years who
      presented in June-August 2007 during hours of high patient volume. To be
      eligible, older males had to have a smoking history or a family history of AAA.
      Patients were excluded if they presented with AAA symptoms, had a previous
      history of AAA screening or repair, had hemodynamic instability, or had an
      altered mental status. Study coordinators completed a brief interview with all
      enrolled subjects to obtain demographic and health information. A credentialed ED
      provider performed the ultrasound (US) screening exam and documented all
      findings. The US director reviewed representative images of the sonographic exam
      for correct visualization and measurement during quality assurance. The ED
      sonographers also completed a survey regarding their attitudes toward AAA
      screening in the ED. The primary study outcomes were the feasibility of AAA
      screening in the ED (screening rate, enrollment rate, US success rate, and
      providers' opinions) and the prevalence of AAA (aortic diameter of > or =3.0 cm)
      in the study sample. RESULTS: During the 12-week study period, the study
      coordinators successfully approached 96% (700/729) of males > 50 years who were
      in the ED during study enrollment hours. Of those approached, 278 were eligible
      (40%), 25% were ineligible, 20% were not at high risk, and for 15% we could not
      determine risk factor status because of altered mental status. Of the 278
      eligible, 196 (70%) underwent an US exam; 10% were not scanned because the
      providers were too busy, and 20% declined participation. Of those scanned, the ED
      sonographer was able to completely visualize and correctly measure the abdominal
      aortas of 71% of subjects. The prevalence rate of AAA in the study sample was
      5.7% (95% confidence interval [CI] = 1.9% to 9.6%), similar to reported rates of
      6 or 7% in other studies. More than half of the ED sonographers reported that US
      screening for AAA improved the quality of ED care (58%) and patient satisfaction
      (63%). However, 47% reported that AAA screening reduced ED efficiency, and 74%
      felt that the ED was not an appropriate setting for routine AAA screening.
      CONCLUSIONS: Routine screening for asymptomatic AAA required substantial ED
      resources for a relatively low success rate of completed screens. The prevalence
      rate of AAA in our ED sample was not significantly different than prevalence
      estimates obtained from older men in the general population. ED sonographers
      reported benefits of screening in terms of improving the quality of emergency
      care and patient satisfaction, but also reported that it reduced operational
      efficiency. For EDs that have problems with crowding, we do not recommend
      implementing a routine screening program for AAA, even among high-risk patients.

PMID- 20053244
TI  - An interdisciplinary initiative to reduce radiation exposure: evaluation of
      appendicitis in a pediatric emergency department with clinical assessment
      supported by a staged ultrasound and computed tomography pathway.
AB  - OBJECTIVES: In the emergency department (ED), a significant amount of radiation
      exposure is due to computed tomography (CT) scans performed for the diagnosis of
      appendicitis. Children are at increased risk of developing cancer from low-dose
      radiation and it is therefore desirable to utilize CT only when appropriate.
      Ultrasonography (US) eliminates radiation but has sensitivity inferior to that of
      CT. We describe an interdisciplinary initiative to use a staged US and CT pathway
      to maximize diagnostic accuracy while minimizing radiation exposure. METHODS:
      This was a retrospective outcomes analysis of patients presenting after hours for
      suspected appendicitis at an academic children's hospital ED over a 6-year
      period. The pathway established US as the initial imaging modality. CT was
      recommended only if US was equivocal. Clinical and pathologic outcomes from ED
      diagnosis and disposition, histopathology and return visits, were correlated with
      the US and CT. ED diagnosis and disposition, pathology, and return visits were
      used to determine outcome. RESULTS: A total of 680 patients met the study
      criteria. A total of 407 patients (60%) followed the pathway. Two-hundred of
      these (49%) were managed definitively without CT. A total of 106 patients (26%)
      had a positive US for appendicitis; 94 (23%) had a negative US. A total of 207
      patients had equivocal US with follow-up CT. A total of 144 patients went to the
      operating room (OR); 10 patients (7%) had negative appendectomies. One case of
      appendicitis was missed (<0.5%). The sensitivity, specificity, negative
      predictive value, and positive predictive values of our staged US-CT pathway were
      99%, 91%, 99%, and 85%, respectively. A total of 228 of 680 patients (34%) had an
      equivocal US with no follow-up CT. Of these patients, 10 (4%) went to the OR with
      one negative appendectomy. A total of 218 patients (32%) were observed clinically
      without complications. CONCLUSIONS: Half of the patients who were treated using
      this pathway were managed with definitive US alone with an acceptable negative
      appendectomy rate (7%) and a missed appendicitis rate of less than 0.5%.
      Visualization of a normal appendix (negative US) was sufficient to obviate the
      need for a CT in the authors' experience. Emergency physicians (EPs) used an
      equivocal US in conjunction with clinical assessment to care for one-third of
      study patients without a CT and with no known cases of missed appendicitis. These
      data suggest that by employing US first on all children needing diagnostic
      imaging for diagnosis of acute appendicitis, radiation exposure may be
      substantially decreased without a decrease in safety or efficacy.

PMID- 20053249
TI  - Serious bacterial infection in recently immunized young febrile infants.
AB  - OBJECTIVE: The objective of this study was to investigate the prevalence of
      serious bacterial infection (SBI) in febrile infants without a source aged 6-12
      weeks who have received immunizations in the preceding 72 hours. METHODS: The
      authors conducted a medical record review of infants aged 6-12 weeks with a fever
      of > or = 38.0 degrees C presenting to the pediatric emergency department (ED)
      over 88 months. Infants were classified either as having received immunizations
      within the 72 hours preceding the ED visit (recent immunization [RI]) or as not
      having received immunizations during this time period (no recent immunization
      [NRI]). Primary outcome of an SBI was based on culture results; only patients
      with a minimum of blood and urine cultures were studied. RESULTS: A total of
      1,978 febrile infants were studied, of whom 213 (10.8%) had received RIs. The
      overall prevalence of definite SBI was 6.6% (95% confidence interval [CI] = 5.5
      to 7.7). The prevalence of definite SBI in NRI infants was 7.0% (95% CI = 5.9 to
      8.3) compared to 2.8% (95% CI = 0.6 to 5.1) in the RI infants. The prevalence of
      definite SBI in febrile infants vaccinated in the preceding 24 hours decreased to
      0.6% (95% CI = 0 to 1.9). The prevalence of definite SBI in febrile infants
      vaccinated greater than 24 hours prior to presentation was 8.9% (95 CI = 1.5 to
      16.4). The relative risk of SBI with RI was 0.41 (95% CI = 0.19 to 0.90). All
      SBIs in the RI infants were urinary tract infections (UTI). CONCLUSIONS: Among
      febrile infants, the prevalence of SBI is less in the initial 24 hours following
      immunizations. However, there is still a substantial risk of UTI. Therefore,
      urine testing should be considered in febrile infants who present within 24 hours
      of immunization. Infants who present greater than 24 hours after immunizations
      with fever should be managed similarly to infants without RIs.

PMID- 20053248
TI  - Variation in the type, rate, and selection of patients for out-of-hospital airway
      procedures among injured children and adults.
AB  - OBJECTIVES: The objective was to compare the type, rate, and selection of injured
      patients for out-of-hospital airway procedures among emergency medical services
      (EMS) agencies in 10 sites across North America. METHODS: The authors analyzed a
      consecutive patient, prospective cohort registry of injured adults and children
      with an out-of-hospital advanced airway attempt, collected from December 1, 2005,
      through February 28, 2007, by 181 EMS agencies in 10 sites across the United
      States and Canada. Advanced airway procedures were defined as orotracheal
      intubation, nasotracheal intubation, supraglottic airway, or cricothyrotomy.
      Airway procedure rates were calculated based on age-specific population values
      for the 10 sites and the number of injured patients with field physiologic
      abnormality (systolic blood pressure of < or = 90 mm Hg, respiratory rate of <10
      or >29 breaths/min, Glasgow Coma Scale [GCS] score of < or = 12). Descriptive
      measures were used to compare patients between sites. RESULTS: A total 1,738
      patients had at least one advanced airway attempt and were included in the
      analysis. There was wide variation between sites in the types of airway
      procedures performed, including orotracheal intubation (63% to 99%), supraglottic
      airways (0 to 27%), nasotracheal intubation (0 to 21%), and cricothyrotomy (0 to
      2%). Use of rapid sequence intubation (RSI) varied from 0% to 65%. The population
      adjusted rates of field airway intervention (by site) ranged from 1.2 to 22.8 per
      100,000 adults and 0.2 to 4.0 per 100,000 children. Among trauma patients with
      physiologic abnormality, some sites performed airway procedures in almost 50% of
      patients, while other sites used these procedures in fewer than 10%. There was
      also large variation in demographic characteristics, physiologic measures,
      mechanism of injury, mode of transport, field cardiopulmonary resuscitation, and
      unadjusted mortality among airway patients. CONCLUSIONS: Among 10 sites across
      North America, there was wide variation in the types of out-of-hospital airway
      procedures performed, population-based rates of airway intervention, and the
      selection of injured patients for such procedures.

PMID- 20053250
TI  - Soft tissue infections and emergency department disposition: predicting the need
      for inpatient admission.
AB  - OBJECTIVES: Little empiric evidence exists to guide emergency department (ED)
      disposition of patients presenting with soft tissue infections. This study's
      objective was to generate a clinical decision rule to predict the need for
      greater than 24-hour hospital admission for patients presenting to the ED with
      soft tissue infection. METHODS: This was a retrospective cohort study of
      consecutive patients presenting to a tertiary care hospital ED with diagnosis of
      nonfacial soft tissue infection. Standardized chart review was used to collect 29
      clinical variables. The primary outcome was >24-hour hospital admission (either
      general admission or ED observation unit), regardless of initial disposition.
      Patients initially discharged home and later admitted for more than 24 hours were
      included in the outcome. Data were analyzed using classification and regression
      tree (CART) analysis and multivariable logistic regression. RESULTS: A total of
      846 patients presented to the ED with nonfacial soft tissue infection. After
      merging duplicate records, 674 patients remained, of which 81 (12%) required
      longer than 24-hour admission. Using CART, the strongest predictors of >24-hour
      admission were patient temperature at ED presentation and mechanism of infection.
      In the multivariable logistic regression model, initial patient temperature (odds
      ratio [OR] for each degree over 37 degrees C = 2.91, 95% confidence interval [CI]
      = 1.65 to 5.12) and history of fever (OR = 3.02, 95% CI = 1.41 to 6.43) remained
      the strongest predictors of hospital admission. Despite these findings, there was
      no combination of factors that reliably identified more than 90% of target
      patients. CONCLUSIONS: Although we were unable to generate a high-sensitivity
      decision rule to identify ED patients with soft tissue infection requiring >24
      hour admission, the presence of a fever (either by initial ED vital signs or by
      history) was the strongest predictor of need for >24-hour hospital stay. These
      findings may help guide disposition of patients presenting to the ED with
      nonfacial soft tissue infections.

PMID- 20053251
TI  - Use of the visual analog scale to rate and monitor severity of nausea in the
      emergency department.
AB  - OBJECTIVES: The objective was to describe the association between verbal
      descriptors of nausea severity and visual analog scale (VAS) ratings in an
      undifferentiated emergency department (ED) population and to calculate the
      minimum clinically significant difference (MCSD) in VAS rating of nausea severity
      in this population. METHODS: A prospective observational study was conducted at
      three EDs on a convenience sample of stable, consenting adult patients presenting
      with nausea as part of their symptom complex. Data included demographics,
      adjectival description of nausea severity (none, mild, moderate, or severe), and
      VAS rating (standard 100-mm line) at enrollment, 30 minutes, and 60 minutes. At
      30 and 60 minutes they were also asked to describe any change in nausea severity
      from the previous rating ("a lot less,""a little less,""the same,""a little
      more,""a lot more"). The MCSD was defined as the average VAS change when a
      patient reported "a little less" or "a little more" nausea. RESULTS: A total of
      247 patients provided 693 matched adjectival ratings and VAS scores. Median age
      was 45 years, and 100 (40%) were male. The median VAS measures for none, mild,
      moderate, and severe nausea were 2, 23, 53, and 83 mm, respectively. VAS
      distributions in the verbal categories were statistically different from each
      other (Spearman rank correlation coefficient = 0.90; p < 0.0001). The MCSD was 22
      mm (95% CI = 20 to 24 mm). CONCLUSIONS: There is very good correlation between
      verbal descriptors of nausea and VAS ratings. The MCSD for VAS nausea ratings in
      an ED population is 22 mm.

PMID- 20053253
TI  - Highlights in emergency medicine medical education research: 2008.
AB  - OBJECTIVES: The purpose of this article is to highlight medical education
      research studies published in 2008 that were methodologically superior and whose
      outcomes were pertinent to teaching and education in emergency medicine. METHODS:
      Through a PubMed search of the English language literature in 2008, 30 medical
      education research studies were independently identified as hypothesis-testing
      investigations and measurements of educational interventions. Six reviewers
      independently rated and scored all articles based on eight anchors, four of which
      related to methodologic criteria. Articles were ranked according to their total
      rating score. A ranking agreement among the reviewers of 83% was established a
      priori as a minimum for highlighting articles in this review. RESULTS: Five
      medical education research studies met the a priori criteria for inclusion and
      are reviewed and summarized here. Four of these employed experimental or quasi
      experimental methodology. Although technology was not a component of the
      structured literature search employed to identify the candidate articles for this
      review, 14 of the articles identified, including four of the five highlighted
      articles, employed or studied technology as a focus of the educational research.
      Overall, 36% of the reviewed studies were supported by funding; three of the
      highlighted articles were funded studies. CONCLUSIONS: This review highlights
      quality medical education research studies published in 2008, with outcomes of
      relevance to teaching and education in emergency medicine. It focuses on research
      methodology, notes current trends in the use of technology for learning in
      emergency medicine, and suggests future avenues for continued rigorous study in
      education.

PMID- 20053252
TI  - Modafinil and zolpidem use by emergency medicine residents.
AB  - OBJECTIVES: The objective was to assess the prevalence and patterns of modafinil
      and zolpidem use among emergency medicine (EM) residents and describe side
      effects resulting from use. METHODS: A voluntary, anonymous survey was
      distributed in February 2006 to EM residents nationally in the context of the
      national American Board of Emergency Medicine in-training examination. Data
      regarding frequency and timing of modafinil and zolpidem use were collected, as
      well as demographic information, reasons for use, side effects, and perceived
      dependence. RESULTS: A total of 133 of 134 residency programs distributed the
      surveys (99%). The response rate was 56% of the total number of EM residents who
      took the in-training examination (2,397/4,281). Past modafinil use was reported
      by 2.4% (57/2,372) of EM residents, with 66.7% (38/57) of those using modafinil
      having initiated their use during residency. Past zolpidem use was reported by
      21.8% (516/2,367) of EM residents, with 15.3% (362/2,367) reporting use in the
      past year and 9.3% (221/2,367) in the past month. A total of 324 of 516 (62.8%)
      of zolpidem users initiated use during residency. Side effects were commonly
      reported by modafinil users (31.0%)-most frequent were palpitations, insomnia,
      agitation, and restlessness. Zolpidem users reported side effects (22.6%)
      including drowsiness, dizziness, headache, hallucinations, depression/mood
      lability, and amnesia. CONCLUSIONS: Zolpidem use is common among EM residents,
      with most users initiating use during residency. Modafinil use is relatively
      uncommon, although most residents using have also initiated use during residency.
      Side effects are commonly reported for both of these agents, and long-term safety
      remains unclear.

PMID- 20053254
TI  - Off-service resident education in the emergency department: outline of a national
      standardized curriculum.
AB  - Although many residency programs mandate at least one rotation in emergency
      medicine (EM), to the best of our knowledge, a standardized curriculum for
      emergency department (ED) rotations for "off-service" residents has not been
      developed. As a result, the experiences of these residents in the ED tend to vary
      during their rotations. To design an off-service EM curriculum, we adopted Kern's
      six-step approach to curriculum development as a conceptual framework. The
      resulting program encompasses clinical experience and didactic sessions through
      which residents are trained in core topics and skills. This knowledge will be
      applicable in the clinical settings in which residents will continue to train and
      ultimately practice their specialty. It is flexible enough to be applicable and
      implementable without being limited by resource availability or faculty
      strengths.

PMID- 20053255
TI  - If you've seen one EMS system, you've seen one EMS system...

PMID- 20053256
TI  - Global crowding: opportunities for regionalization in emergency care.

PMID- 20053257
TI  - International emergency medicine: a review of the literature from 2008.
AB  - As the specialty of emergency medicine (EM) continues to evolve in countries
      around the world, and as interest in international emergency medicine (IEM)
      continues to grow within the United States, the IEM Literature Review Group
      recognizes a need for a high-quality, consolidated, and easily accessible
      evidence base of literature. In response to that need, the group created an
      annual publication that strives to provide readers with access to the highest
      quality and most relevant IEM research. This publication represents our fourth
      annual review, covering the top 26 IEM research articles published in 2008.
      Articles were selected for the review according to explicit, predetermined
      criteria that include both methodologic quality and perceived impact of the
      research. It is our hope that this annual review will act as a forum for
      disseminating best practices while also stimulating further research in the field
      of IEM.

PMID- 20053258
TI  - Kaizen: a method of process improvement in the emergency department.
AB  - INTRODUCTION: Recent position statements from health care organizations have
      placed a strong emphasis on continuous quality improvement (CQI). CQI finds many
      of its roots in kaizen, which emphasizes small, low-cost, low-risk improvements.
      Based on the successful Kaizen Programs at organizations such as Toyota, the
      authors thought the emergency department (ED) would be an ideal environment to
      benefit from such a program. OBJECTIVES: The authors sought to create a CQI
      program using a suggestion-based model that did not require a large time
      commitment, was easy to implement, and had the potential to empower all
      physicians in the department. It would not take the place of other improvement
      efforts, but instead augment them. The hypothesis was that such a program would
      foster sustainable engagement of emergency physicians in system improvement
      efforts and lead to a continuous stream of low-cost implementable system
      improvement interventions. METHODS: A CQI program was created for the physician
      staff of the Department of Emergency Medicine at Vanderbilt University Medical
      Center, focusing on a suggestion-based model using kaizen philosophy. Lectures
      teaching kaizen philosophy were presented. Over the past 4 years, a methodology
      was developed utilizing a Web-based application, the Kaizen Tracker, which aids
      in the submission and implementation of suggestions that are called kaizen
      initiatives (KIs). The characteristics of the KIs submitted, details regarding
      resident and faculty participation, and the effectiveness of the Kaizen Tracker
      were retrospectively reviewed. RESULTS: There were 169, 105, and 101 KIs placed
      in the postimplementation calendar years 2006, 2007, and 2008, respectively.
      Seventy-six percent of KIs submitted thus far have identified a "process
      problem." Fifty-three percent of KIs submitted have led to operational changes
      within the ED. Ninety-three percent of the resident physicians entered at least
      one KI, and 73% of these residents submitted more than one KI. Sixty-nine percent
      of the attendings entered at least one KI, and 89% of these attendings submitted
      more than one KI. CONCLUSIONS: Over the past 4 years, the Kaizen Program at
      Vanderbilt has been widely and frequently used within the ED. It has resulted in
      over 400 changes in our adult ED system and has met the challenge of using CQI to
      drive ED improvements. There are limitations to this study, including the fact
      that its impact on patient outcomes remains unknown. However, this Kaizen Program
      may be an excellent tool for other departments to assist with quality improvement
      and should be studied with a multicenter prospective approach.

PMID- 20053259
TI  - Using a discrete-event simulation to balance ambulance availability and demand in
      static deployment systems.
AB  - OBJECTIVES: To improve ambulance response time, matching ambulance availability
      with the emergency demand is crucial. To maintain the standard of 90% of response
      times within 9 minutes, the authors introduce a discrete-event simulation method
      to estimate the threshold for expanding the ambulance fleet when demand increases
      and to find the optimal dispatching strategies when provisional events create
      temporary decreases in ambulance availability. METHODS: The simulation model was
      developed with information from the literature. Although the development was
      theoretical, the model was validated on the emergency medical services (EMS)
      system of Tainan City. The data are divided: one part is for model development,
      and the other for validation. For increasing demand, the effect was modeled on
      response time when call arrival rates increased. For temporary availability
      decreases, the authors simulated all possible alternatives of ambulance
      deployment in accordance with the number of out-of-routine-duty ambulances and
      the durations of three types of mass gatherings: marathon races (06:00-10:00 hr),
      rock concerts (18:00-22:00 hr), and New Year's Eve parties (20:00-01:00 hr).
      RESULTS: Statistical analysis confirmed that the model reasonably represented the
      actual Tainan EMS system. The response-time standard could not be reached when
      the incremental ratio of call arrivals exceeded 56%, which is the threshold for
      the Tainan EMS system to expand its ambulance fleet. When provisional events
      created temporary availability decreases, the Tainan EMS system could spare at
      most two ambulances from the standard configuration, except between 20:00 and
      01:00, when it could spare three. The model also demonstrated that the current
      Tainan EMS has two excess ambulances that could be dropped. The authors suggest
      dispatching strategies to minimize the response times in routine daily
      emergencies. CONCLUSIONS: Strategies of capacity management based on this model
      improved response times. The more ambulances that are out of routine duty, the
      better the performance of the optimal strategies that are based on this model.

PMID- 20053260
TI  - Commentary to "the difficult airway" resident portfolio.

PMID- 20053261
TI  - Emergency medicine residents do not document detailed neurologic examinations.
AB  - OBJECTIVES: Physical examinations performed by residents in many specialties are
      often incomplete and inaccurate. This report assessed the documentation of the
      neurologic examination performed by emergency medicine (EM) residents when
      examining patients with potential psychiatric or neurologic chief complaints.
      METHODS: A retrospective chart review of neurologic examinations documented by EM
      residents was performed. An eight-item neurologic examination score was created
      and analyzed by resident postgraduate year. A linear mixed model was used to
      determine if differences in neurologic examination scores existed between
      resident year, type of complaint, and resident year and type of complaint. A one
      point difference in scores was considered clinically important. RESULTS: A total
      of 384 charts were reviewed. An average of 4.26 items (95% confidence interval
      [CI] = 3.91 to 4.62) out of a possible eight were documented that did not vary by
      resident year of training (p = 0.08). An effect was found for type of complaint.
      Documentation was lower for psychiatric than for neurologic complaints: mean
      score for psychiatric complaints 3.97 vs. mean score for neurologic complaints
      4.55 (difference -0.58, 95% CI = -1.02 to -0.14). No interaction was found for
      type of complaint and resident year. A clustering effect was identified for
      individual residents. CONCLUSIONS: Emergency medicine residents do not document
      detailed neurologic examinations on patients with neurologic or psychiatric
      complaints. Individual resident variation contributes to this documentation.

PMID- 20053262
TI  - Use of an automated device for external chest compressions by first-aid workers
      unfamiliar with the device: a step toward public access?
AB  - OBJECTIVE: The objective was to establish the feasibility of using an automated
      external chest compression (ECC) device among first-aid workers unfamiliar with
      the device. METHODS: Eighty first-aid workers unfamiliar with the Autopulse ECC
      device were randomized into three groups. Group 1 was given two explanatory
      illustrations on device use. Group 2 was given four explanatory illustrations.
      Group 3 was shown a 5-minute video on the placement and use of the device and
      allowed to handle the device for 5 minutes. The time taken to place and start the
      device on a mannequin was recorded. RESULTS: There was no significant difference
      among the three groups with regard to age, sex ratio, experience, and time
      elapsed since their last training session. No mistakes in device placement were
      made by any of the groups. All 80 participants started ECC in less than 160
      seconds. There was no significant difference between Groups 1 and 2 in time taken
      to place or start the device (medians and 25-75 percentiles = 72 [54-112] vs. 86
      [46-130] seconds and 154 [103-183] vs. 156 [120-197] seconds, respectively).
      However, Group 3 first-aid workers obtained significantly better results (19 [16
      26] seconds to place and 48 [40-65] seconds to start; p<0.0001). CONCLUSIONS: An
      automated ECC device can be rapidly placed and used by first-aid workers
      unfamiliar with the device. In the light of these results, use of the device by
      the general public can be envisaged.

PMID- 20053263
TI  - Emergency department diagnosis of pneumothorax using goal-directed ultrasound.

PMID- 20053264
TI  - Left main coronary artery stenting during cardiopulmonary resuscitation: a life
      saving experience.

PMID- 20053267
TI  - A migraine variant with abdominal colic and Alice in Wonderland syndrome: a case
      report and review.
AB  - BACKGROUND: Abdominal migraine is a commonly described migraine variant in
      children and young adults, but associations with Alice in Wonderland syndrome and
      lilliputian hallucinations are exceptional. CASE PRESENTATION: A 20 years-old
      male experienced frequent and prolonged attacks of abdominal colic associated
      with autonomic manifestations started at the age of ten. At the age of 17, he
      additionally described prolonged attacks (>or= 7 days) of distortions of shape,
      size or position of objects or subjects. He said "Quite suddenly, objects appear
      small and distant (teliopsia) or large and close (peliopsia). I feel as I am
      getting shorter and smaller "shrinking" and also the size of persons are not
      longer than my index finger (a lilliputian proportion). Sometimes I see the blind
      in the window or the television getting up and down, or my leg or arm is
      swinging. I may hear the voices of people quite loud and close or faint and far.
      Occasionally, I experience attacks of migrainous headache associated with eye
      redness, flashes of lights and a feeling of giddiness. I am always conscious to
      the intangible changes in myself and my environment". There is a strong family
      history of common migraine. Clinical examination, brain-MRI and EEG were normal.
      Transcranial magnetic stimulation and evoked potentials revealed enhanced
      cortical excitability in multiple brain regions. Treatment with valproate
      resulted in marked improvement of all clinical and neurophysiological
      abnormalities. CONCLUSIONS: The association between the two migraine variants
      (abdominal migraine and Alice in Wonderland Syndrome) might have clinical,
      pathophysiological and management implications. I think this is the first
      description in the literature.

PMID- 20053268
TI  - Prediction of microRNAs affecting mRNA expression during retinal development.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules (~22 nucleotides) which
      have been shown to play an important role both in development and in maintenance
      of adult tissue. Conditional inactivation of miRNAs in the eye causes loss of
      visual function and progressive retinal degeneration. In addition to inhibiting
      translation, miRNAs can mediate degradation of targeted mRNAs. We have previously
      shown that candidate miRNAs affecting transcript levels in a tissue can be
      deduced from mRNA microarray expression profiles. The purpose of this study was
      to predict miRNAs which affect mRNA levels in developing and adult retinal tissue
      and to confirm their expression. RESULTS: Microarray expression data from ciliary
      epithelial retinal stem cells (CE-RSCs), developing and adult mouse retina were
      generated or downloaded from public repositories. Analysis of gene expression
      profiles detected the effects of multiple miRNAs in CE-RSCs and retina. The
      expression of 20 selected miRNAs was confirmed by RT-PCR and the cellular
      distribution of representative candidates analyzed by in situ hybridization. The
      expression levels of miRNAs correlated with the significance of their predicted
      effects upon mRNA expression. Highly expressed miRNAs included miR-124, miR-125a,
      miR-125b, miR-204 and miR-9. Over-expression of three miRNAs with significant
      predicted effects upon global mRNA levels resulted in a decrease in mRNA
      expression of five out of six individual predicted target genes assayed.
      CONCLUSIONS: This study has detected the effect of miRNAs upon mRNA expression in
      immature and adult retinal tissue and cells. The validity of these observations
      is supported by the experimental confirmation of candidate miRNA expression and
      the regulation of predicted target genes following miRNA over-expression.
      Identified miRNAs are likely to be important in retinal development and function.
      Misregulation of these miRNAs might contribute to retinal degeneration and
      disease. Conversely, manipulation of their expression could potentially be used
      as a therapeutic tool in the future.

PMID- 20053269
TI  - Variable viral clearance despite adequate ganciclovir plasma levels during
      valganciclovir treatment for cytomegalovirus disease in D+/R- transplant
      recipients.
AB  - BACKGROUND: Valganciclovir, the oral prodrug of ganciclovir, has been
      demonstrated equivalent to iv ganciclovir for CMV disease treatment in solid
      organ transplant recipients. Variability in ganciclovir exposure achieved with
      valganciclovir could be implicated as a contributing factor for explaining
      variations in the therapeutic response. This prospective observational study
      aimed to correlate clinical and cytomegalovirus (CMV) viral load response
      (DNAemia) with ganciclovir plasma concentrations in patients treated with
      valganciclovir for CMV infection/disease. METHODS: Seven CMV D+/R- transplant
      recipients (4 kidney, 2 liver and 1 heart) were treated with valganciclovir
      (initial dose was 900-1800 mg/day for 3-6.5 weeks, followed by 450-900 mg/day for
      2-9 weeks). DNAemia was monitored by real time quantitative PCR and ganciclovir
      plasma concentration was measured at trough (Ctrough) and 3 h after drug
      administration (C3h) by HPLC. RESULTS: Four patients presented with CMV syndrome,
      two had CMV tissue-invasive disease after prophylaxis discontinuation, and one
      liver recipient was treated pre-emptively for asymptomatic rising CMV viral load
      5 weeks post-transplantation in the absence of prophylaxis. CMV DNAemia decreased
      during the first week of treatment in all recipients except in one patient
      (median decrease: -1.2 log copies/mL, range: -1.8 to 0) despite satisfactory
      ganciclovir exposure (AUC0-12 = 48 mgxh/L, range for the 7 patients: 40-118
      mgxh/L). Viral clearance was obtained in five patients after a median of time of
      34 days (range: 28-82 days). Two patients had recurrent CMV disease despite
      adequate ganciclovir exposure (65 mgxh/L, range: 44-118 mgxh/L). CONCLUSIONS:
      Valganciclovir treatment for CMV infection/disease in D+/R- transplant recipients
      can thus result in variable viral clearance despite adequate ganciclovir plasma
      concentrations, probably correlating inversely with anti-CMV immune responses
      after primary infection.

PMID- 20053270
TI  - PREDICT: a new UK prognostic model that predicts survival following surgery for
      invasive breast cancer.
AB  - INTRODUCTION: The aim of this study was to develop and validate a prognostication
      model to predict overall and breast cancer specific survival for women treated
      for early breast cancer in the UK. METHODS: Using the Eastern Cancer Registration
      and Information Centre (ECRIC) dataset, information was collated for 5,694 women
      who had surgery for invasive breast cancer in East Anglia from 1999 to 2003.
      Breast cancer mortality models for oestrogen receptor (ER) positive and ER
      negative tumours were derived from these data using Cox proportional hazards,
      adjusting for prognostic factors and mode of cancer detection (symptomatic versus
      screen-detected). An external dataset of 5,468 patients from the West Midlands
      Cancer Intelligence Unit (WMCIU) was used for validation. RESULTS: Differences in
      overall actual and predicted mortality were <1% at eight years for ECRIC (18.9%
      vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator
      characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast
      cancer specific actual and predicted mortality were <1% at eight years for ECRIC
      (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC
      of 0.84 and 0.82 respectively. Model calibration was good for both ER positive
      and negative models although the ER positive model provided better discrimination
      (AUC 0.82) than ER negative (AUC 0.75). CONCLUSIONS: We have developed a
      prognostication model for early breast cancer based on UK cancer registry data
      that predicts breast cancer survival following surgery for invasive breast cancer
      and includes mode of detection for the first time. The model is well calibrated,
      provides a high degree of discrimination and has been validated in a second UK
      patient cohort.

PMID- 20053271
TI  - Breathlessness is associated with urinary incontinence in men: A community-based
      study.
AB  - BACKGROUND: Urinary incontinence (UI) is a distressing problem for older people.
      To investigate the relationship between UI and respiratory symptoms among middle
      aged and older men, a community-based study was conducted in Japan. METHODS: A
      convenience sample of 668 community-dwelling men aged 40 years or above was
      recruited from middle and southern Japan. The International Consultation on
      Incontinence Questionnaire-Short Form, the Medical Research Council's dyspnoea
      scale and the Australian Lung Foundation's Feeling Short of Breath scale, were
      administered by face-to-face interviews to ascertain their UI status and
      respiratory symptoms. RESULTS: The overall prevalence of UI was 7.6%, with urge
      type leakage (59%) being most common among the 51 incontinent men. The presence
      of respiratory symptoms was significantly higher among incontinent men than those
      without the condition, especially for breathlessness (45% versus 30%, p = 0.025).
      The odds of UI for breathlessness was 2.11 (95% confidence interval 1.10-4.06)
      after accounting for age, body mass index, smoking and alcohol drinking status of
      each individual. CONCLUSIONS: The findings suggested a significant association
      between UI and breathlessness in middle-aged and older men.

PMID- 20053272
TI  - A tutorial on pilot studies: the what, why and how.
AB  - Pilot studies for phase III trials - which are comparative randomized trials
      designed to provide preliminary evidence on the clinical efficacy of a drug or
      intervention - are routinely performed in many clinical areas. Also commonly know
      as "feasibility" or "vanguard" studies, they are designed to assess the safety of
      treatment or interventions; to assess recruitment potential; to assess the
      feasibility of international collaboration or coordination for multicentre
      trials; to increase clinical experience with the study medication or intervention
      for the phase III trials. They are the best way to assess feasibility of a large,
      expensive full-scale study, and in fact are an almost essential pre-requisite.
      Conducting a pilot prior to the main study can enhance the likelihood of success
      of the main study and potentially help to avoid doomed main studies. The
      objective of this paper is to provide a detailed examination of the key aspects
      of pilot studies for phase III trials including: 1) the general reasons for
      conducting a pilot study; 2) the relationships between pilot studies, proof-of
      concept studies, and adaptive designs; 3) the challenges of and misconceptions
      about pilot studies; 4) the criteria for evaluating the success of a pilot study;
      5) frequently asked questions about pilot studies; 7) some ethical aspects
      related to pilot studies; and 8) some suggestions on how to report the results of
      pilot investigations using the CONSORT format.

PMID- 20053274
TI  - Simple versus composite indicators of socioeconomic status in resource allocation
      formulae: the case of the district resource allocation formula in Malawi.
AB  - BACKGROUND: The district resource allocation formula in Malawi was recently
      reviewed to include stunting as a proxy measure of socioeconomic status. In many
      countries where the concept of need has been incorporated in resource allocation,
      composite indicators of socioeconomic status have been used. In the Malawi case,
      it is important to ascertain whether there are differences between using single
      variable or composite indicators of socioeconomic status in allocations made to
      districts, holding all other factors in the resource allocation formula constant.
      METHODS: Principal components analysis was used to calculate asset indices for
      all districts from variables that capture living standards using data from the
      Malawi Multiple Indicator Cluster Survey 2006. These were normalized and used to
      weight district populations. District proportions of national population weighted
      by both the simple and composite indicators were then calculated for all
      districts and compared. District allocations were also calculated using the two
      approaches and compared. RESULTS: The two types of indicators are highly
      correlated, with a spearman rank correlation coefficient of 0.97 at the 1% level
      of significance. For 21 out of the 26 districts included in the study,
      proportions of national population weighted by the simple indicator are higher by
      an average of 0.6 percentage points. For the remaining 5 districts, district
      proportions of national population weighted by the composite indicator are higher
      by an average of 2 percentage points. Though the average percentage point
      differences are low and the actual allocations using both approaches highly
      correlated (rho of 0.96), differences in actual allocations exceed 10% for 8
      districts and have an average of 4.2% for the remaining 17. For 21 districts
      allocations based on the single variable indicator are higher. CONCLUSIONS:
      Variations in district allocations made using either the simple or composite
      indicators of socioeconomic status are not statistically different to recommend
      one over the other. However, the single variable indicator is favourable for its
      ease of computation.

PMID- 20053273
TI  - Study protocol of the YOU CALL--WE CALL TRIAL: impact of a multimodal support
      intervention after a "mild" stroke.
AB  - BACKGROUND: More than 60% of new strokes each year are "mild" in severity and
      this proportion is expected to rise in the years to come. Within our current
      health care system those with "mild" stroke are typically discharged home within
      days, without further referral to health or rehabilitation services other than
      advice to see their family physician. Those with mild stroke often have limited
      access to support from health professionals with stroke-specific knowledge who
      would typically provide critical information on topics such as secondary stroke
      prevention, community reintegration, medication counselling and problem solving
      with regard to specific concerns that arise. Isolation and lack of knowledge may
      lead to a worsening of health problems including stroke recurrence and
      unnecessary and costly health care utilization.The purpose of this study is to
      assess the effectiveness, for individuals who experience a first "mild" stroke,
      of a sustainable, low cost, multimodal support intervention (comprising
      information, education and telephone support)--"WE CALL" compared to a passive
      intervention (providing the name and phone number of a resource person available
      if they feel the need to)--"YOU CALL", on two primary outcomes: unplanned-use of
      health services for negative events and quality of life. METHOD/DESIGN: We will
      recruit 384 adults who meet inclusion criteria for a first mild stroke across six
      Canadian sites. Baseline measures will be taken within the first month after
      stroke onset. Participants will be stratified according to comorbidity level and
      randomised to one of two groups: YOU CALL or WE CALL. Both interventions will be
      offered over a six months period. Primary outcomes include unplanned use of heath
      services for negative event (frequency calendar) and quality of life (EQ-5D and
      Quality of Life Index). Secondary outcomes include participation level (LIFE-H),
      depression (Beck Depression Inventory II) and use of health services for health
      promotion or prevention (frequency calendar). Blind assessors will gather data at
      mid-intervention, end of intervention and one year follow up. DISCUSSION: If
      effective, this multimodal intervention could be delivered in both urban and
      rural environments. For example, existing infrastructure such as regional stroke
      centers and existing secondary stroke prevention clinics, make this intervention,
      if effective, deliverable and sustainable. TRIAL REGISTRATION: ISRCTN95662526.

PMID- 20053275
TI  - Molecular pedomorphism underlies craniofacial skeletal evolution in Antarctic
      notothenioid fishes.
AB  - BACKGROUND: Pedomorphism is the retention of ancestrally juvenile traits by
      adults in a descendant taxon. Despite its importance for evolutionary change,
      there are few examples of a molecular basis for this phenomenon. Notothenioids
      represent one of the best described species flocks among marine fishes, but their
      diversity is currently threatened by the rapidly changing Antarctic climate.
      Notothenioid evolutionary history is characterized by parallel radiations from a
      benthic ancestor to pelagic predators, which was accompanied by the appearance of
      several pedomorphic traits, including the reduction of skeletal mineralization
      that resulted in increased buoyancy. RESULTS: We compared craniofacial skeletal
      development in two pelagic notothenioids, Chaenocephalus aceratus and
      Pleuragramma antarcticum, to that in a benthic species, Notothenia coriiceps, and
      two outgroups, the threespine stickleback and the zebrafish. Relative to these
      other species, pelagic notothenioids exhibited a delay in pharyngeal bone
      development, which was associated with discrete heterochronic shifts in skeletal
      gene expression that were consistent with persistence of the chondrogenic program
      and a delay in the osteogenic program during larval development. Morphological
      analysis also revealed a bias toward the development of anterior and ventral
      elements of the notothenioid pharyngeal skeleton relative to dorsal and posterior
      elements. CONCLUSIONS: Our data support the hypothesis that early shifts in the
      relative timing of craniofacial skeletal gene expression may have had a
      significant impact on the adaptive radiation of Antarctic notothenioids into
      pelagic habitats.

PMID- 20053276
TI  - PyMix--the python mixture package--a tool for clustering of heterogeneous
      biological data.
AB  - BACKGROUND: Cluster analysis is an important technique for the exploratory
      analysis of biological data. Such data is often high-dimensional, inherently
      noisy and contains outliers. This makes clustering challenging. Mixtures are
      versatile and powerful statistical models which perform robustly for clustering
      in the presence of noise and have been successfully applied in a wide range of
      applications. RESULTS: PyMix - the Python mixture package implements algorithms
      and data structures for clustering with basic and advanced mixture models. The
      advanced models include context-specific independence mixtures, mixtures of
      dependence trees and semi-supervised learning. PyMix is licenced under the GNU
      General Public licence (GPL). PyMix has been successfully used for the analysis
      of biological sequence, complex disease and gene expression data. CONCLUSIONS:
      PyMix is a useful tool for cluster analysis of biological data. Due to the
      general nature of the framework, PyMix can be applied to a wide range of
      applications and data sets.

PMID- 20053277
TI  - A Rac1 inhibitory peptide suppresses antibody production and paw swelling in the
      murine collagen-induced arthritis model of rheumatoid arthritis.
AB  - INTRODUCTION: The Rho family GTPase Rac1 regulates cytoskeletal rearrangements
      crucial for the recruitment, extravasation and activation of leukocytes at sites
      of inflammation. Rac1 signaling also promotes the activation and survival of
      lymphocytes and osteoclasts. Therefore, we assessed the ability of a cell
      permeable Rac1 carboxy-terminal inhibitory peptide to modulate disease in mice
      with collagen-induced arthritis (CIA). METHODS: CIA was induced in DBA/1 mice,
      and in either early or chronic disease, mice were treated three times per week by
      intraperitoneal injection with control peptide or Rac1 inhibitory peptide.
      Effects on disease progression were assessed by measurement of paw swelling.
      Inflammation and joint destruction were examined by histology and radiology.
      Serum levels of anti-collagen type II antibodies were measured by enzyme-linked
      immunosorbent assay. T-cell phenotypes and activation were assessed by
      fluorescence-activated cell sorting analysis. Results were analyzed using Mann
      Whitney U and unpaired Student t tests. RESULTS: Treatment of mice with Rac1
      inhibitory peptide resulted in a decrease in paw swelling in early disease and to
      a lesser extent in more chronic arthritis. Of interest, while joint destruction
      was unaffected by Rac1 inhibitory peptide, anti-collagen type II antibody
      production was significantly diminished in treated mice, in both early and
      chronic arthritis. Ex vivo, Rac1 inhibitory peptide suppressed T-cell
      receptor/CD28-dependent production of tumor necrosis factor alpha, interferon
      gamma and interleukin-17 by T cells from collagen-primed mice, and reduced
      induction of ICOS and CD154, T-cell costimulatory proteins important for B-cell
      help. CONCLUSIONS: The data suggest that targeting of Rac1 with the Rac1 carboxy
      terminal inhibitory peptide may suppress T-cell activation and autoantibody
      production in autoimmune disease. Whether this could translate into clinically
      meaningful improvement remains to be shown.

PMID- 20053278
TI  - Descriptive distribution and phylogenetic analysis of feline infectious
      peritonitis virus isolates of Malaysia.
AB  - The descriptive distribution and phylogeny of feline coronaviruses (FCoVs) were
      studied in cats suspected of having feline infectious peritonitis (FIP) in
      Malaysia. Ascitic fluids and/or biopsy samples were subjected to a reverse
      transcription polymerase chain reaction (RT-PCR) targeted for a conserved region
      of 3'untranslated region (3'UTR) of the FCoV genome. Eighty nine percent of the
      sampled animals were positive for the presence of FCoV. Among the FCoV positive
      cats, 80% of cats were males and 64% were below 2 years of age. The FCoV positive
      cases included 56% domestic short hair (DSH), 40% Persian, and 4% Siamese cats.
      The nucleotide sequences of 10 selected amplified products from FIP cases were
      determined. The sequence comparison revealed that the field isolates had 96%
      homology with a few point mutations. The extent of homology decreased to 93% when
      compared with reference strains. The overall branching pattern of phylogenetic
      tree showed two distinct clusters, where all Malaysian isolates fall into one
      main genetic cluster. These findings provided the first genetic information of
      FCoV in Malaysia.

PMID- 20053279
TI  - A pre-operative elevated neutrophil: lymphocyte ratio does not predict survival
      from oesophageal cancer resection.
AB  - BACKGROUND: Elevated pre-operative neutrophil: lymphocyte ratio (NLR) has been
      identified as a predictor of survival in patients with hepatocellular and
      colorectal cancer. The aim of this study was to examine the prognostic value of
      an elevated preoperative NLR following resection for oesophageal cancer. METHODS:
      Patients who underwent resection for oesophageal carcinoma from June 1997 to
      September 2007 were identified from a local cancer database. Data on
      demographics, conventional prognostic markers, laboratory analyses including
      blood count results, and histopathology were collected and analysed. RESULTS: A
      total of 294 patients were identified with a median age at diagnosis of 65.2 (IQR
      59-72) years. The median pre-operative time of blood sample collection was three
      days (IQR 1-8). The median neutrophil count was 64.2 x 10-9/litre, median
      lymphocyte count 23.9 x 10-9/litre, whilst the NLR was 2.69 (IQR 1.95-4.02). NLR
      did not prove to be a significant predictor of number of involved lymph nodes
      (Cox regression, p = 0.754), disease recurrence (p = 0.288) or death (Cox
      regression, p = 0.374). Furthermore, survival time was not significantly
      different between patients with high (>or= 3.5) or low (< 3.5) NLR (p = 0.49).
      CONCLUSION: Preoperative NLR does not appear to offer useful predictive ability
      for outcome, disease-free and overall survival following oesophageal cancer
      resection.

PMID- 20053280
TI  - Virulence regulator AphB enhances toxR transcription in Vibrio cholerae.
AB  - BACKGROUND: Vibrio cholerae is the causative agent of cholera. Extensive studies
      reveal that complicated regulatory cascades regulate expression of virulence
      genes, the products of which are required for V. cholerae to colonize and cause
      disease. In this study, we investigated the expression of the key virulence
      regulator ToxR under different conditions. RESULTS: We found that compared to
      that of wild type grown to stationary phase, the toxR expression was lower in an
      aphB mutant strain. AphB has been previously shown to be a key virulence
      regulator that is required to activate the expression of tcpP. When expressed
      constitutively, AphB is able to activate the toxR promoter. Furthermore, gel
      shift analysis indicates that AphB binds toxR promoter region directly. We also
      characterize the effect of AphB on the levels of the outer membrane porins OmpT
      and OmpU, which are known to be regulated by ToxR. CONCLUSIONS: Our data indicate
      that V. cholerae possesses an additional regulatory loop that use AphB to
      activate the expression of two virulence regulators, ToxR and TcpP, which
      together control the expression of the master virulence regulator ToxT.

PMID- 20053281
TI  - Malaria control under the Taliban regime: insecticide-treated net purchasing,
      coverage, and usage among men and women in eastern Afghanistan.
AB  - BACKGROUND: Scaling up insecticide-treated mosquito net (ITN) coverage is a key
      malaria control strategy even in conflict-affected countries 12. Socio-economic
      factors influence access to ITNs whether subsidized or provided free to users.
      This study examines reported ITN purchasing, coverage, and usage in eastern
      Afghanistan and explores women's access to health information during the Taliban
      regime (1996-2001). This strengthens the knowledge base on household-level health
      choices in complex-emergency settings. METHODS: Fifteen focus group discussions
      (FGDs) and thirty in-depth interviews were conducted with men and women from ITN
      owning and non-owning households. FGDs included rank ordering, pile sorting and
      focused discussion of malaria knowledge and ITN purchasing. Interviews explored
      general health issues, prevention and treatment practices, and women's malaria
      knowledge and concerns. Seven key informant interviews with health-related
      workers and a concurrent survey of 200 ITN-owning and 214 non-owning households
      were used to clarify or quantify findings. RESULTS: Malaria knowledge was similar
      among men and women and ITN owners and non-owners. Women reported obtaining
      health information through a variety of sources including clinic staff, their
      husbands who had easier access to information, and particularly female peers.
      Most participants considered ITNs very desirable, though not usually household
      necessities. ITN owners reported more household assets than non-owners. Male ITN
      owners and non-owners ranked rugs and ITNs as most desired, while women ranked
      personal assets such as jewellery highest. While men were primarily responsible
      for household decision-making and purchasing, older women exerted considerable
      influence. Widow-led and landless households reported most difficulties
      purchasing ITNs. Most participants wanted to buy ITNs only if they could cover
      all household members. When not possible, preferential usage was given to women
      and children. CONCLUSIONS: Despite restricted access to health facilities and
      formal education, Afghan women were surprisingly knowledgeable about the causes
      of malaria and the value of ITNs in prevention. Inequities in ITN usage were
      noted between rather than within households, with some unable to afford even one
      ITN and others not wanting ITNs unless all household members could be protected.
      Malaria knowledge thus appears a lesser barrier to ITN purchasing and coverage in
      eastern Afghanistan than are pricing and distribution strategies.

PMID- 20053282
TI  - Reduction of CPR artifacts in the ventricular fibrillation ECG by coherent line
      removal.
AB  - BACKGROUND: Interruption of cardiopulmonary resuscitation (CPR) impairs the
      perfusion of the fibrillating heart, worsening the chance for successful
      defibrillation. Therefore ECG-analysis during ongoing chest compression could
      provide a considerable progress in comparison with standard analysis techniques
      working only during "hands-off" intervals. METHODS: For the reduction of CPR
      related artifacts in ventricular fibrillation ECG we use a localized version of
      the coherent line removal algorithm developed by Sintes and Schutz. This method
      can be used for removal of periodic signals with sufficiently coupled harmonics,
      and can be adapted to specific situations by optimal choice of its parameters
      (e.g., the number of harmonics considered for analysis and reconstruction). Our
      testing was done with 14 different human ventricular fibrillation (VF) ECGs,
      whose fibrillation band lies in a frequency range of [1 Hz, 5 Hz]. The VF-ECGs
      were mixed with 12 different ECG-CPR-artifacts recorded in an animal experiment
      during asystole. The length of each of the ECG-data was chosen to be 20 sec, and
      testing was done for all 168 = 14 x 12 pairs of data. VF-to-CPR ratio was chosen
      as -20 dB, -15 dB, -10 dB, -5 dB, 0 dB, 5 dB and 10 dB. Here -20 dB corresponds
      to the highest level of CPR-artifacts. RESULTS: For non-optimized coherent line
      removal based on signals with a VF-to-CPR ratio of -20 dB, -15 dB, -10 dB, -5 dB
      and 0 dB, the signal-to-noise gains (SNR-gains) were 9.3 +/- 2.4 dB, 9.4 +/- 2.4
      dB, 9.5 +/- 2.5 dB, 9.3 +/- 2.5 dB and 8.0 +/- 2.7 (mean +/- std, n = 168),
      respectively. Characteristically, an original VF-to-CPR ratio of -10 dB,
      corresponds to a variance ratio var(VF):var(CPR) = 1:10. An improvement by 9.5 dB
      results in a restored VF-to-CPR ratio of -0.5 dB, corresponding to a variance
      ratio var(VF):var(CPR) = 1:1.1, the variance of the CPR in the signal being
      reduced by a factor of 8.9. DISCUSSION: The localized coherent line removal
      algorithm uses the information of a single ECG channel. In contrast to multi
      channel algorithms, no additional information such as thorax impedance, blood
      pressure, or pressure exerted on the sternum during CPR is required. Predictors
      of defibrillation success such as mean and median frequency of VF-ECGs containing
      CPR-artifacts are prone to being governed by the harmonics of the artifacts.
      Reduction of CPR-artifacts is therefore necessary for determining reliable values
      for estimators of defibrillation success. CONCLUSIONS: The localized coherent
      line removal algorithm reduces CPR-artifacts in VF-ECG, but does not eliminate
      them. Our SNR-improvements are in the same range as offered by multichannel
      methods of Rheinberger et al., Husoy et al. and Aase et al. The latter two
      authors dealt with different ventricular rhythms (VF and VT), whereas here we
      dealt with VF, only. Additional developments are necessary before the algorithm
      can be tested in real CPR situations.

PMID- 20053283
TI  - Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.
AB  - BACKGROUND: It was previously demonstrated that the dipeptide carnosine inhibits
      growth of cultured cells isolated from patients with malignant glioma. In the
      present work we investigated whether carnosine also affects tumor growth in vivo
      and may therefore be considered for human cancer therapy. RESULTS: A mouse model
      was used to investigate whether tumor growth in vivo can be inhibited by
      carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human
      epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal
      skin of nude mice, and tumor growth in treated animals was compared to control
      mice. In two independent experiments nude mice that received tumor cells received
      a daily intra peritoneal injection of 500 microl of 1 M carnosine solution.
      Measurable tumors were detected 12 days after injection. Aggressive tumor growth
      in control animals, that received a daily intra peritoneal injection of NaCl
      solution started at day 16 whereas aggressive growth in mice treated with
      carnosine was delayed, starting around day 19. A significant effect of carnosine
      on tumor growth was observed up to day 24. Although carnosine was not able to
      completely prevent tumor growth, a microscopic examination of tumors revealed
      that those from carnosine treated animals had a significant lower number of
      mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects
      proliferation in vivo. CONCLUSION: As a naturally occurring substance with a high
      potential to inhibit growth of malignant cells in vivo, carnosine should be
      considered as a potential anti-cancer drug. Further experiments should be
      performed in order to understand how carnosine acts at the molecular level.

PMID- 20053284
TI  - Ovalbumin-induced plasma interleukin-4 levels are reduced in ceramide kinase
      deficient DO11.10 RAG1-/- mice.
AB  - Ceramide kinase (CERK) produces the bioactive lipid ceramide-1-phosphate (C1P)
      and is a key regulator of ceramide and dihydroceramide levels. It is likely that
      CERK and C1P play a role in inflammatory processes but the cells involved and the
      mechanisms used remain to be clarified. In particular, the impact of CERK on T
      cell biology has not been studied so far. Here, we used Cerk-/- mice backcrossed
      with DO11.10/RAG1-/- mice to probe the effect of CERK ablation on T-cell
      activation. Levels of interleukin (IL)-2, IL-4, IL-5, IL-13, of tumor necrosis
      factor (TNF)-alpha, and of interferon (INF)-gamma were recorded following
      ovalbumin challenge in vivo and using ovalbumin-treated splenocytes ex- vivo.
      Absence of CERK led to a significant decrease in the production of IL-4, thus
      suggesting that CERK may polarize T cells towards the TH2 cell subtype. However,
      the importance of CERK to TH2 cell biology will have to be investigated further
      because in a model of asthma, which is TH2-cell driven, Cerk-/- mice responded
      like wild-type animals.

PMID- 20053285
TI  - Plasma CCN2/connective tissue growth factor is associated with right ventricular
      dysfunction in patients with neuroendocrine tumors.
AB  - BACKGROUND: Carcinoid heart disease, a known complication of neuroendocrine
      tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease
      has traditionally been defined by the degree of valvular involvement. Right
      ventricular (RV) dysfunction due to mural involvement may also be a
      manifestation. Connective tissue growth factor (CCN2) is elevated in many
      fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to
      investigate the relationship between plasma CCN2 and valvular and mural
      involvement in carcinoid heart disease. METHODS: Echocardiography was performed
      in 69 patients with neuroendocrine tumors. RV function was assessed using tissue
      Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an
      enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared
      and Fisher's exact tests were used to compare groups where appropriate. Linear
      regression was used to evaluate correlation. RESULTS: Mean strain was -21% +/- 5.
      Thirty-three patients had reduced RV function (strain > -20%, mean -16% +/- 3).
      Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR).
      Thirty-six patients had normal or mildly reduced RV function (strain < or = -20%,
      mean -25% +/- 3). There was a significant inverse correlation between RV function
      and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function
      had higher plasma CCN2 levels than those with normal or mildly reduced RV
      function (p < 0.001). Plasma CCN2 > or = 77 microg/L was an independent predictor
      of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88%
      sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was
      elevated in patients with mild or greater TR/PR compared to those with no or
      minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe
      TR/PR (p = 0.03). CONCLUSIONS: Elevated plasma CCN2 levels are associated with RV
      dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in
      neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its
      earliest stages.

PMID- 20053286
TI  - Risk factors for breast cancer in postmenopausal Caucasian and Chinese-Canadian
      women.
AB  - INTRODUCTION: Striking differences exist between countries in the incidence of
      breast cancer. The causes of these differences are unknown, but because incidence
      rates change in migrants, they are thought to be due to lifestyle rather than
      genetic differences. The goal of this cross-sectional study was to examine breast
      cancer risk factors in populations with different risks for breast cancer.
      METHODS: We compared breast cancer risk factors among three groups of
      postmenopausal Canadian women at substantially different risk of developing
      breast cancer - Caucasians (N = 413), Chinese women born in the West or who
      migrated to the West before age 21 (N = 216), and recent Chinese migrants (N =
      421). Information on risk factors and dietary acculturation were collected by
      telephone interviews using questionnaires, and anthropometric measurements were
      taken at a home visit. RESULTS: Compared to Caucasians, recent Chinese migrants
      weighed on average 14 kg less, were 6 cm shorter, had menarche a year later, were
      more often parous, less often had a family history of breast cancer or a benign
      breast biopsy, a higher Chinese dietary score, and a lower Western dietary score.
      For most of these variables, Western born Chinese and early Chinese migrants had
      values intermediate between those of Caucasians and recent Chinese migrants. We
      estimated five-year absolute risks for breast cancer using the Gail Model and
      found that risk estimates in Caucasians would be reduced by only 11% if they had
      the risk factor profile of recent Chinese migrants for the risk factors in the
      Gail Model. CONCLUSIONS: Our results suggest that in addition to the risk factors
      in the Gail Model, there likely are other factors that also contribute to the
      large difference in breast cancer risk between Canada and China.

PMID- 20053287
TI  - An integrated functional genomic study of acute phenobarbital exposure in the
      rat.
AB  - BACKGROUND: Non-genotoxic carcinogens are notoriously difficult to identify as
      they do not damage DNA directly and have diverse modes of action, necessitating
      long term in vivo studies. The early effects of the classic rodent non-genotoxic
      hepatocarcinogen phenobarbital have been investigated in the Fisher rat using a
      combination of metabolomics and transcriptomics, to investige early stage
      mechanistic changes that are predictive of longer term pathology. RESULTS: Liver
      and blood plasma were profiled across 14 days, and multivariate statistics used
      to identify perturbed pathways. Both metabolomics and transcriptomics detected
      changes in the liver which were dose dependent, even after one day of exposure.
      Integration of the two datasets associated perturbations with specific pathways.
      Hepatic glycogen was decreased due to a decrease in synthesis, and plasma
      triglycerides were decreased due to an increase in fatty acid uptake by the
      liver. Hepatic succinate was increased and this was associated with increased
      heme biosynthesis. Glutathione synthesis was also increased, presumably in
      response to oxidative stress. Liquid Chromatography Mass Spectrometry
      demonstrated a remodeling of lipid species, possibly resulting from proliferation
      of the smooth endoplasmic reticulum. CONCLUSIONS: The data fusion of metabolomic
      and transcriptomic changes proved to be a highly sensitive approach for
      monitoring early stage changes in altered hepatic metabolism, oxidative stress
      and cytochrome P450 induction simultaneously. This approach is particularly
      useful in interpreting changes in metabolites such as succinate which are hubs of
      metabolism.

PMID- 20053288
TI  - The dynamic architecture of the metabolic switch in Streptomyces coelicolor.
AB  - BACKGROUND: During the lifetime of a fermenter culture, the soil bacterium S.
      coelicolor undergoes a major metabolic switch from exponential growth to
      antibiotic production. We have studied gene expression patterns during this
      switch, using a specifically designed Affymetrix genechip and a high-resolution
      time-series of fermenter-grown samples. RESULTS: Surprisingly, we find that the
      metabolic switch actually consists of multiple finely orchestrated switching
      events. Strongly coherent clusters of genes show drastic changes in gene
      expression already many hours before the classically defined transition phase
      where the switch from primary to secondary metabolism was expected. The main
      switch in gene expression takes only 2 hours, and changes in antibiotic
      biosynthesis genes are delayed relative to the metabolic rearrangements.
      Furthermore, global variation in morphogenesis genes indicates an involvement of
      cell differentiation pathways in the decision phase leading up to the commitment
      to antibiotic biosynthesis. CONCLUSIONS: Our study provides the first detailed
      insights into the complex sequence of early regulatory events during and
      preceding the major metabolic switch in S. coelicolor, which will form the
      starting point for future attempts at engineering antibiotic production in a
      biotechnological setting.

PMID- 20053289
TI  - Benign ancient schwannoma of the abdominal wall: an unwanted birthday present.
AB  - BACKGROUND: There has been a recent growth in the use of whole body Computerised
      Tomography (CT) scans in the private sector as a screening test for asymptomatic
      disease. This is despite scant evidence to show any positive effect on morbidity
      or mortality. There has been concern raised over the possible harms of the test
      in terms of radiation exposure as well as the risk and anxiety of further
      investigation and treatment for the large numbers of benign lesions identified.
      CASE PRESENTATION: A healthy 64 year old lady received a privately funded whole
      body CT scan for her birthday which revealed an incidental mass in the right
      iliac fossa. This was investigated with further imaging and colonoscopy and as
      confident diagnosis could not be made, eventually excised. Histology demonstrated
      this to be a benign ancient schwannoma and we believe this to be the first
      reported case of an abdominal wall schwannoma in the English literature
      CONCLUSIONS: Ancient schwannomas are rare tumours of the peripheral nerve sheaths
      more usually found in the head, neck and flexor surfaces of extremities. They are
      a subtype of classical schwannomas with a predominance of degenerative changes.
      Our case highlights the pitfalls of such screening tests in demonstrating benign
      disease and subjecting patients to what turns out to be unnecessary invasive
      investigation and treatment. It provides evidence as to the consequences of the
      large number of false positive results that are created by blind CT scanning of
      asymptomatic patients i.e. its tendency to detect pseudodiesease rather than
      affect survival rates. Should the number of scans increase there may be an
      unnecessary burden on NHS resources due to the large numbers of benign lesions
      picked up, that are then referred for further investigation.

PMID- 20053290
TI  - A few strong connections: optimizing information retention in neuronal
      avalanches.
AB  - BACKGROUND: How living neural networks retain information is still incompletely
      understood. Two prominent ideas on this topic have developed in parallel, but
      have remained somewhat unconnected. The first of these, the "synaptic
      hypothesis," holds that information can be retained in synaptic connection
      strengths, or weights, between neurons. Recent work inspired by statistical
      mechanics has suggested that networks will retain the most information when their
      weights are distributed in a skewed manner, with many weak weights and only a few
      strong ones. The second of these ideas is that information can be represented by
      stable activity patterns. Multineuron recordings have shown that sequences of
      neural activity distributed over many neurons are repeated above chance levels
      when animals perform well-learned tasks. Although these two ideas are compelling,
      no one to our knowledge has yet linked the predicted optimum distribution of
      weights to stable activity patterns actually observed in living neural networks.
      RESULTS: Here, we explore this link by comparing stable activity patterns from
      cortical slice networks recorded with multielectrode arrays to stable patterns
      produced by a model with a tunable weight distribution. This model was previously
      shown to capture central features of the dynamics in these slice networks,
      including neuronal avalanche cascades. We find that when the model weight
      distribution is appropriately skewed, it correctly matches the distribution of
      repeating patterns observed in the data. In addition, this same distribution of
      weights maximizes the capacity of the network model to retain stable activity
      patterns. Thus, the distribution that best fits the data is also the distribution
      that maximizes the number of stable patterns. CONCLUSIONS: We conclude that local
      cortical networks are very likely to use a highly skewed weight distribution to
      optimize information retention, as predicted by theory. Fixed distributions
      impose constraints on learning, however. The network must have mechanisms for
      preserving the overall weight distribution while allowing individual connection
      strengths to change with learning.

PMID- 20053291
TI  - MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on
      genome rearrangement.
AB  - BACKGROUND: Ortholog assignment is a critical and fundamental problem in
      comparative genomics, since orthologs are considered to be functional
      counterparts in different species and can be used to infer molecular functions of
      one species from those of other species. MSOAR is a recently developed high
      throughput system for assigning one-to-one orthologs between closely related
      species on a genome scale. It attempts to reconstruct the evolutionary history of
      input genomes in terms of genome rearrangement and gene duplication events. It
      assumes that a gene duplication event inserts a duplicated gene into the genome
      of interest at a random location (i.e., the random duplication model). However,
      in practice, biologists believe that genes are often duplicated by tandem
      duplications, where a duplicated gene is located next to the original copy (i.e.,
      the tandem duplication model). RESULTS: In this paper, we develop MSOAR 2.0, an
      improved system for one-to-one ortholog assignment. For a pair of input genomes,
      the system first focuses on the tandemly duplicated genes of each genome and
      tries to identify among them those that were duplicated after the speciation
      (i.e., the so-called inparalogs), using a simple phylogenetic tree reconciliation
      method. For each such set of tandemly duplicated inparalogs, all but one gene
      will be deleted from the concerned genome (because they cannot possibly appear in
      any one-to-one ortholog pairs), and MSOAR is invoked. Using both simulated and
      real data experiments, we show that MSOAR 2.0 is able to achieve a better
      sensitivity and specificity than MSOAR. In comparison with the well-known genome
      scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the
      orthology information extracted from the well-known whole-genome multiple
      alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the
      specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real
      data experiments, it is actually better than that of InParanoid in the simulation
      tests. CONCLUSIONS: Our preliminary experimental results demonstrate that MSOAR
      2.0 is a highly accurate tool for one-to-one ortholog assignment between closely
      related genomes. The software is available to the public for free and included as
      online supplementary material.

PMID- 20053292
TI  - Using a Markov simulation model to assess the impact of changing trends in
      coronary heart disease incidence on requirements for coronary artery
      revascularization procedures in Western Australia.
AB  - BACKGROUND: The population incidence of coronary heart disease (CHD) has been
      declining in Australia and many other countries. This decline has been due to
      reduced population levels of risk factors for CHD and improved medical care for
      those at higher risk of CHD. However, there are signs that there may be a slowing
      down or even reversal in the decline of CHD incidence due to the 'obesity
      epidemic' and other factors and this will have implications for the requirements
      for surgical treatments for those with CHD. METHODS: Using a validated Markov
      simulation model applied to the population of Western Australia, different CHD
      incidence trend scenarios were developed to explore the effect of changing CHD
      incidence on requirements for coronary artery bypass graft (CABG) and
      percutaneous coronary interventions (PCI), together known as coronary artery
      revascularization procedures (CARPs). RESULTS: The most dominant component of CHD
      incidence is the risk of CHD hospital admission for those with no history of CHD
      and if this risk leveled off and the trends in all other risks continued
      unchanged, then the projected numbers of CABGs and PCIs are only minimally
      changed. Further, the changes in the projected numbers remained small even when
      this risk was increased by 20 percent (although it is an unlikely scenario).
      However, when the other CHD incidence components that had also been declining,
      namely, the risk of CABG and that of CHD death for those with no history of CHD,
      were also projected to level off as these were declining in 1998-2000 and the
      risk of PCI for those with no history of CHD (which was already increasing) was
      projected to further increase by 5 percent, it had a substantial effect on the
      projected numbers of CARPs. CONCLUSION: There needs to be dramatic changes to
      several CHD incidence components before it has a substantial impact on the
      projected requirements for CARPs. Continued monitoring of CHD incidence and also
      the mix of initial presentation of CHD incidence is required in order to
      understand changes to future CARP requirements.

PMID- 20053293
TI  - Plasmodium falciparum resistance to anti-malarial drugs in Papua New Guinea:
      evaluation of a community-based approach for the molecular monitoring of
      resistance.
AB  - BACKGROUND: Molecular monitoring of parasite resistance has become an important
      complementary tool in establishing rational anti-malarial drug policies.
      Community surveys provide a representative sample of the parasite population and
      can be carried out more rapidly than accrual of samples from clinical cases, but
      it is not known whether the frequencies of genetic resistance markers in clinical
      cases differ from those in the overall population, or whether such community
      surveys can provide good predictions of treatment failure rates. METHODS: Between
      2003 and 2005, in vivo drug efficacy of amodiaquine or chloroquine plus
      sulphadoxine-pyrimethamine was determined at three sites in Papua New Guinea. The
      genetic drug resistance profile (i.e., 33 single nucleotide polymorphisms in
      Plasmodium falciparum crt, mdr1, dhfr, dhps, and ATPase6) was concurrently
      assessed in 639 community samples collected in the catchment areas of the
      respective health facilities by using a DNA microarray-based method. Mutant
      allele and haplotype frequencies were determined and their relationship with
      treatment failure rates at each site in each year was investigated. RESULTS: PCR
      corrected in vivo treatment failure rates were between 12% and 28% and varied by
      site and year with variable longitudinal trends. In the community samples, the
      frequencies of mutations in pfcrt and pfmdr1 were high and did not show
      significant changes over time. Mutant allele frequencies in pfdhfr were moderate
      and those in pfdhps were low. No mutations were detected in pfATPase6. There was
      much more variation between sites than temporal, within-site, variation in allele
      and haplotype frequencies. This variation did not correlate well with treatment
      failure rates. Allele and haplotype frequencies were very similar in clinical and
      community samples from the same site. CONCLUSIONS: The relationship between
      parasite genetics and in vivo treatment failure rate is not straightforward. The
      frequencies of genetic anti-malarial resistance markers appear to be very similar
      in community and clinical samples, but cannot be used to make precise predictions
      of clinical outcome. Thus, indicators based on molecular data have to be
      considered with caution and interpreted in the local context, especially with
      regard to prior drug usage and level of pre-existing immunity. Testing community
      samples for molecular drug resistance markers is a complementary tool that should
      help decision-making for the best treatment options and appropriate potential
      alternatives.

PMID- 20053294
TI  - Influenza virus infection among pediatric patients reporting diarrhea and
      influenza-like illness.
AB  - BACKGROUND: Influenza is a major cause of morbidity and hospitalization among
      children. While less often reported in adults, gastrointestinal symptoms have
      been associated with influenza in children, including abdominal pain, nausea,
      vomiting, and diarrhea. METHODS: From September 2005 and April 2008, pediatric
      patients in Indonesia presenting with concurrent diarrhea and influenza-like
      illness were enrolled in a study to determine the frequency of influenza virus
      infection in young patients presenting with symptoms less commonly associated
      with an upper respiratory tract infection (URTI). Stool specimens and upper
      respiratory swabs were assayed for the presence of influenza virus. RESULTS:
      Seasonal influenza A or influenza B viral RNA was detected in 85 (11.6%) upper
      respiratory specimens and 21 (2.9%) of stool specimens. Viable influenza B virus
      was isolated from the stool specimen of one case. During the time of this study,
      human infections with highly pathogenic avian influenza A (H5N1) virus were
      common in the survey area. However, among 733 enrolled subjects, none had
      evidence of H5N1 virus infection. CONCLUSIONS: The detection of influenza viral
      RNA and viable influenza virus from stool suggests that influenza virus may be
      localized in the gastrointestinal tract of children, may be associated with
      pediatric diarrhea and may serve as a potential mode of transmission during
      seasonal and epidemic influenza outbreaks.

PMID- 20053295
TI  - Statistical method on nonrandom clustering with application to somatic mutations
      in cancer.
AB  - BACKGROUND: Human cancer is caused by the accumulation of tumor-specific
      mutations in oncogenes and tumor suppressors that confer a selective growth
      advantage to cells. As a consequence of genomic instability and high levels of
      proliferation, many passenger mutations that do not contribute to the cancer
      phenotype arise alongside mutations that drive oncogenesis. While several
      approaches have been developed to separate driver mutations from passengers, few
      approaches can specifically identify activating driver mutations in oncogenes,
      which are more amenable for pharmacological intervention. RESULTS: We propose a
      new statistical method for detecting activating mutations in cancer by
      identifying nonrandom clusters of amino acid mutations in protein sequences. A
      probability model is derived using order statistics assuming that the location of
      amino acid mutations on a protein follows a uniform distribution. Our statistical
      measure is the differences between pair-wise order statistics, which is
      equivalent to the size of an amino acid mutation cluster, and the probabilities
      are derived from exact and approximate distributions of the statistical measure.
      Using data in the Catalog of Somatic Mutations in Cancer (COSMIC) database, we
      have demonstrated that our method detects well-known clusters of activating
      mutations in KRAS, BRAF, PI3K, and beta-catenin. The method can also identify new
      cancer targets as well as gain-of-function mutations in tumor suppressors.
      CONCLUSIONS: Our proposed method is useful to discover activating driver
      mutations in cancer by identifying nonrandom clusters of somatic amino acid
      mutations in protein sequences.

PMID- 20053296
TI  - The differential mediating effects of pain and depression on the physical and
      mental dimension of quality of life in Hong Kong Chinese adults.
AB  - OBJECTIVE: The impact of pain and depression on health-related quality of life
      (QoL) is widely investigated, yet the pain-depression interactions on QoL remain
      unclear. This study aims to examine the pain-depression-QoL mediation link.
      METHODS: Pain severity were assessed in a sample of Chinese professional teachers
      (n = 385). The subjects were also assessed on depressive symptoms and QoL.
      Regression models were fitted to evaluate the pain-depression-QoL relationships.
      RESULTS: About 44% of the sample had 3-5 painful areas in the past 3 months.
      Shoulder pain (60%) and headache (53%) were common painful areas. The results of
      regression analyses showed that pain mediated the effects of depression on the
      mental aspect of QoL (standardized beta = -0.111; Sobel test: z = -3.124, p <
      0.005) whereas depression mediated the effects of pain on the physical aspect of
      QoL (standardized beta = -0.026; Sobel test: z = -4.045, p < 0.001). CONCLUSIONS:
      Our study offered tentative evidence that pain and depression impacted
      differently on the mental and physical aspect of QoL. As these findings were
      based on a Chinese teacher sample, future studies should employ more
      representative samples across cultures to verify the present data.

PMID- 20053297
TI  - Global transcriptional analysis of nitrogen fixation and ammonium repression in
      root-associated Pseudomonas stutzeri A1501.
AB  - BACKGROUND: Biological nitrogen fixation is highly controlled at the
      transcriptional level by regulatory networks that respond to the availability of
      fixed nitrogen. In many diazotrophs, addition of excess ammonium in the growth
      medium results in immediate repression of nif gene transcription. Although the
      regulatory cascades that control the transcription of the nif genes in
      proteobacteria have been well investigated, there are limited data on the
      kinetics of ammonium-dependent repression of nitrogen fixation. RESULTS: Here we
      report a global transcriptional profiling analysis of nitrogen fixation and
      ammonium repression in Pseudomonas stutzeri A1501, a root-associated and nitrogen
      fixing bacterium. A total of 166 genes, including those coding for the global
      nitrogen regulation (Ntr) and Nif-specific regulatory proteins, were upregulated
      under nitrogen fixation conditions but rapidly downregulated as early as 10 min
      after ammonium shock. Among these nitrogen fixation-inducible genes, 95 have
      orthologs in each of Azoarcus sp. BH72 and Azotobacter vinelandii AvoP. In
      particular, a 49-kb expression island containing nif and other associated genes
      was markedly downregulated by ammonium shock. Further functional characterization
      of pnfA, a new NifA-sigma54-dependent gene chromosomally linked to nifHDK, is
      reported. This gene encodes a protein product with an amino acid sequence similar
      to that of five hypothetical proteins found only in diazotrophic strains. No
      noticeable differences in the transcription of nifHDK were detected between the
      wild type strain and pnfA mutant. However, the mutant strain exhibited a
      significant decrease in nitrogenase activity under microaerobic conditions and
      lost its ability to use nitrate as a terminal electron acceptor for the support
      of nitrogen fixation under anaerobic conditions. CONCLUSIONS: Based on our
      results, we conclude that transcriptional regulation of nif gene expression in
      A1501 is mediated by the nif-specific and ntr gene regulatory systems.
      Furthermore, microarray and mutational analyses revealed that many genes of
      unknown function may play some essential roles in controlling the expression or
      activity of nitrogenase. The findings presented here establish the foundation for
      further studies on the physiological function of nitrogen fixation-inducible
      genes.

PMID- 20053298
TI  - Death to sepsis: targeting apoptosis pathways in sepsis.
AB  - Sepsis is a significant public health problem and is one of the leading causes of
      death in critically ill patients admitted to the intensive care unit. The cost,
      both in terms of lives lost and annual healthcare expenditures, from sepsis is
      staggering. Unfortunately, despite an increasing understanding of the unique
      molecular pathobiology of sepsis, mortality has remained more or less stable over
      the past decade. Moreover, promising therapies in preclinical models of sepsis
      have universally failed to live up to initial expectations in subsequent clinical
      trials. Multiple studies have demonstrated that apoptosis plays a major role in
      the pathobiology of sepsis and acute lung injury, making the apoptosis pathway an
      attractive target for therapy. Herein, the role of apoptosis in sepsis is briefly
      discussed, highlighting studies with one potential therapeutic agent targeting
      the apoptosis pathway.

PMID- 20053299
TI  - Disinfection of the hospital water supply: a hidden risk to dialysis patients.
AB  - Water suitable for drinking is unsuited for use in the preparation of
      haemodialysis fluid and undergoes additional treatment. The primary component of
      the additional treatment is reverse osmosis, which does not remove low-molecular
      weight contaminants, and the water treatment system must contain carbon beds or
      filters to ensure effective removal of such contaminants. The recent article by
      Bek and colleagues highlights an unrecognised issue with respect to chemicals
      that may be added to the water within hospitals to ensure that the distribution
      network is free of pathogens (for example, Legionella, pseudomonas, and
      mycobacteria) and underlines the need for personnel responsible for dialysis in a
      renal or intensive care setting to be aware of any potential effects that
      disinfection of the hospital water treatment system may have on the product water
      used in the preparation of dialysis fluid. Such awareness requires communication
      and the sharing of information between clinical and facilities staff.

PMID- 20053300
TI  - Standardisation of data collection in traumatic brain injury: key to the future?
AB  - Great variability exists in data collection and coding of variables in studies on
      traumatic brain injury (TBI). This confounds comparison of results and analysis
      of data across studies. The difficulties in performing a meta-analysis of
      individual patient data were recently illustrated in the IMPACT project
      (International Mission on Prognosis and Clinical Trial Design in TBI): merging
      data from 11 studies involved over 10 person years of work. However, these
      studies did confirm the great potential for advancing the field by this approach.
      Although randomized controlled trials remain the prime approach for investigating
      treatment effects, these can never address the many uncertainties concerning
      multiple treatment modalities in TBI. Pooling data from different studies may
      provide the best possible source of evidence we can get in a cost efficient way.
      Standardisation of data collection and coding is essential to this purpose.
      Recommendations hereto have been proposed by an interagency initiative in the US.
      These proposals deserve to be taken forward at an international level. This
      initiative may well constitute one of the most important steps forwards, paving
      the road for harvesting successful results in the near future.

PMID- 20053301
TI  - Bench-to-bedside review: delirium in ICU patients - importance of sleep
      deprivation.
AB  - Delirium occurs frequently in critically ill patients and has been associated
      with both short-term and long-term consequences. Efforts to decrease delirium
      prevalence have been directed at identifying and modifying its risk factors. One
      potentially modifiable risk factor is sleep deprivation. Critically ill patients
      are known to experience poor sleep quality with severe sleep fragmentation and
      disruption of sleep architecture. Poor sleep while in the intensive care unit is
      one of the most common complaints of patients who survive critical illness. The
      relationship between delirium and sleep deprivation remains controversial.
      However, studies have demonstrated many similarities between the clinical and
      physiologic profiles of patients with delirium and sleep deprivation. This
      article aims to review the literature, the clinical and neurobiologic
      consequences of sleep deprivation, and the potential relationship between sleep
      deprivation and delirium in intensive care unit patients. Sleep deprivation may
      prove to be a modifiable risk factor for the development of delirium with
      important implications for the acute and long-term outcome of critically ill
      patients.

PMID- 20053302
TI  - Forward genetics in Tribolium castaneum: opening new avenues of research in
      arthropod biology.
AB  - A recent paper in BMC Biology reports the first large-scale insertional
      mutagenesis screen in a non-drosophilid insect, the red flour beetle Tribolium
      castaneum. This screen marks the beginning of a non-biased, 'forward genetics'
      approach to the study of genetic mechanisms operating in Tribolium.

PMID- 20053303
TI  - Heterogeneity of human effector CD4+ T cells.
AB  - For many years the heterogeneity of CD4+ T-helper (Th) cells has been limited to
      Th1 and Th2 cells, which have been considered not only to be responsible for
      different types of protective responses, but also for the pathogenesis of many
      disorders. Th1 cells are indeed protective against intracellular microbes and
      they are thought to play a pathogenic role in organ-specific autoimmune and other
      chronic inflammatory disorders. Th2 cells provide protection against helminths,
      but are also responsible for the pathogenesis of allergic diseases. The
      identification and cloning of new cytokines has allowed one to enlarge the series
      of functional subsets of CD4+ Th effector cells. In particular, CD4+ Th cells
      producing IL-17 and IL-22, named Th17, have been initially implicated in the
      pathogenesis of many chronic inflammatory disorders instead of Th1 cells.
      However, the more recent studies in both humans and mice suggest that Th17 cells
      exhibit a high plasticity toward Th1 cells and that both Th17 and Th1 cells may
      be pathogenic. More recently, another two subsets of effector CD4+ Th cells,
      named Th9 and Th22 cells, have been described, even if their pathophysiological
      meaning is still unclear. Despite the heterogeneity of CD4+ effector Th cells
      being higher than previously thought and some of their subsets exhibiting high
      plasticity, the Th1/Th2 paradigm still maintains a strong validity.

PMID- 20053304
TI  - The bacterial pathogen Listeria monocytogenes: an emerging model in prokaryotic
      transcriptomics.
AB  - A major challenge in bacterial pathogenesis is understanding the molecular basis
      of the switch from saprophytism to virulence. Following a recent whole-genome
      transcriptomic analysis using tiling arrays, an article published in BMC Genomics
      reports the first use of RNA-seq in Listeria monocytogenes in order to identify
      genes controlled by sigma B, a transcriptional regulator with a critical role in
      virulence.

PMID- 20053305
TI  - Scribble at the crossroads.
AB  - Although proteins involved in determining apical-basal cell polarity have been
      directly linked to tumorigenesis, their precise roles in this process remain
      unclear. A recent report in BMC Biology clarifies the signaling pathways that
      control cell polarity, proliferation and apoptosis downstream of the tumor
      suppressor and apical-basal polarity determinant Scribble.

PMID- 20053307
TI  - Therapeutic ultrasound as treatment for chronic rhinosinusitis: preliminary
      observations.
AB  - BACKGROUND: Bacterial biofilms have been implicated in the pathogenesis of
      chronic rhinosinusitis. In the laboratory setting, ultrasound is effective in
      disrupting such biofilms; however, few clinical studies have evaluated the role
      of therapeutic ultrasound in chronic rhinosinusitis. OBJECTIVE: This study was
      performed to investigate the short-term effectiveness of therapeutic ultrasound
      as a treatment modality for chronic rhinosinusitis. METHODS: Twenty-two patients
      with a positive history of chronic rhinosinusitis, according to the criteria set
      out by the Rhinosinusitis Task Force, together with a previous computed
      tomography scan compatible with a diagnosis of chronic rhinosinusitis, and who
      had failed previous, aggressive medical management, were treated with therapeutic
      pulsed ultrasound at 1 MHz two to three days per week for six sessions. Patients
      completed an assessment of individual sinus symptom severity and the 20-Item Sino
      Nasal Outcome Test questionnaire before treatment, prior to session four and
      after completion of session six. RESULTS: Two patients were unable to complete
      the study protocol. After completion of session six, 18 patients had experienced
      improvement in symptoms, while two patients noted a worsening of symptoms. Median
      percentage improvement of the total overall symptom score was 16.7 per cent
      (Wilcoxon signed rank, p < 0.001). The 20-Item Sino-Nasal Outcome Test score
      improved by 34.1 per cent (Wilcoxon signed rank, p < 0.0001). CONCLUSION: This
      study demonstrated a significant improvement in chronic rhinosinusitis symptoms
      after a six-session course of pulsed ultrasound therapy. Treatment with
      ultrasound alone or combined with antibiotics may provide a strategy to target
      biofilms on the sinus mucosa. Therapeutic ultrasound warrants further
      investigation as a potential treatment modality for chronic rhinosinusitis.

PMID- 20053306
TI  - The PIN-FORMED (PIN) protein family of auxin transporters.
AB  - The PIN-FORMED (PIN) proteins are secondary transporters acting in the efflux of
      the plant signal molecule auxin from cells. They are asymmetrically localized
      within cells and their polarity determines the directionality of intercellular
      auxin flow. PIN genes are found exclusively in the genomes of multicellular
      plants and play an important role in regulating asymmetric auxin distribution in
      multiple developmental processes, including embryogenesis, organogenesis, tissue
      differentiation and tropic responses. All PIN proteins have a similar structure
      with amino- and carboxy-terminal hydrophobic, membrane-spanning domains separated
      by a central hydrophilic domain. The structure of the hydrophobic domains is well
      conserved. The hydrophilic domain is more divergent and it determines eight
      groups within the protein family. The activity of PIN proteins is regulated at
      multiple levels, including transcription, protein stability, subcellular
      localization and transport activity. Different endogenous and environmental
      signals can modulate PIN activity and thus modulate auxin-distribution-dependent
      development. A large group of PIN proteins, including the most ancient members
      known from mosses, localize to the endoplasmic reticulum and they regulate the
      subcellular compartmentalization of auxin and thus auxin metabolism. Further work
      is needed to establish the physiological importance of this unexpected mode of
      auxin homeostasis regulation. Furthermore, the evolution of PIN-based transport,
      PIN protein structure and more detailed biochemical characterization of the
      transport function are important topics for further studies.

PMID- 20053308
TI  - New repositioning techniques for benign paroxysmal positional vertigo: the Li
      repositioning manoeuvres.
AB  - Benign paroxysmal positional vertigo can be treated by repositioning manoeuvres.
      Current manoeuvres can be cumbersome to perform and require determination of the
      canal affected, usually by assessing nystagmus direction on provocation. We
      developed a new series of manoeuvres to manage benign paroxysmal positional
      vertigo of each semicircular canal. The canal affected, and thus the manoeuvre
      used in each case, was determined by the patient's subjective report of vertigo
      on provocative head positioning. The reported manoeuvres were utilised in 216
      patients, with an excellent rate of symptom resolution (96.7 per cent). The Li
      particle repositioning manoeuvres are effective, reliable and simply performed
      alternatives for the management of benign paroxysmal positional vertigo.

PMID- 20053309
TI  - Anaesthesia for microlaryngeal and laser laryngeal surgery: impact of subglottic
      jet ventilation.
AB  - OBJECTIVE: Over the past 20 years, jet ventilation techniques have been developed
      to enable safe and controlled microlaryngoscopy and the accurate treatment of
      laryngeal pathology. This study examined how advances in jet ventilation tube
      design have facilitated safe endolaryngeal surgery. STUDY DESIGN: The study
      documented the development and use of the Jockjet subglottic jet ventilation tube
      system at the Prince of Wales Hospital, Sydney. The new system consisted of two
      components: a Teflon tube with an outer diameter of 4 mm at the larynx, and a
      companion ventilator. The facility for end-tidal carbon dioxide and distal
      airways pressure monitoring was incorporated via dedicated channels. The Venturi
      jet was produced via a covered tip to prevent trauma to the tracheal mucosa.
      SETTING: The Prince of Wales and Sydney Children's Hospitals, incorporated with
      The University of New South Wales. PATIENTS: From June 2002 to March 2008
      inclusive, 1000 consecutive patients underwent microlaryngeal surgery at this
      institution. Subglottic jet ventilation, via the Jockjet tube, was employed for
      332 patients. MAIN OUTCOME MEASURES: Anaesthetic safety and intra-operative
      surgical access. RESULTS: In all the 332 patients observed, surgical access was
      optimised and no adverse anaesthetic outcomes were encountered. CONCLUSION:
      Subglottic jet ventilation facilitates safe airway management during
      microlaryngeal and laser laryngeal surgery.

PMID- 20053310
TI  - A rare cause of Horner syndrome.
AB  - OBJECTIVES: To demonstrate the importance of thorough investigation of patients
      with Horner syndrome, and to explain the relevant anatomy. CASE REPORT: A 46-year
      old man presented with right-sided Horner syndrome. No other abnormality was
      found. Magnetic resonance imaging showed calcification of the stylohyoid
      ligament, with a pseudoarthrosis in the mid-portion of the ligament. This
      pseudoarthrosis was displacing and compressing the internal carotid artery and
      the adjacent sympathetic chain, causing Horner syndrome. CONCLUSION: In this
      case, magnetic resonance imaging was invaluable in elucidating the cause of the
      Horner syndrome. This is the first described case of pseudoarthrosis of a
      calcified stylohyoid ligament causing Horner syndrome.

PMID- 20053311
TI  - Diffusion-weighted magnetic resonance imaging: its uses in otolaryngology.

PMID- 20053312
TI  - Endoscopic Caldwell-Luc technique.
AB  - This report describes a combined approach to the maxillary sinus, used to deal
      with mucosal pathology. The technique uses a powered microdebrider with angled
      endoscopes and is minimally invasive. It is cost-effective and offers the
      potential for decreased surgical time, reduced post-operative healing time and
      reduced post-operative morbidity.

PMID- 20053313
TI  - The 14-item Paediatric Throat Disorders Outcome Test: a valid, sensitive,
      reliable, parent-reported outcome measure for paediatric throat disorders.
AB  - OBJECTIVES: We modified and abbreviated a pre-existing research questionnaire,
      the Tonsil and Adenoid Health Status Instrument, to make it suitable for rapid
      completion as a disease-specific, health-related quality of life research tool
      for children with tonsil and adenoid disease in the UK. We determined the main
      psychometric properties of the resulting 14-item Paediatric Throat Disorders
      Outcome Test. DESIGN, SETTING AND PARTICIPANTS: Pre- and post-operative
      questionnaires were completed by the parents of children with throat disorders
      referred to two large hospitals. We included children with recurrent tonsillitis
      and with obstructive sleep apnoea. A separate cohort of healthy children of
      comparable age range was also studied. MAIN OUTCOME MEASURES: The test's internal
      consistency and responsiveness were analysed and its construct validity
      documented via known-group differences. RESULTS: A total of 126 completed
      questionnaires were received from the hospital referral group. The children's
      mean age was 6.5 years (range one to 16). The 40 unaffected children were well
      matched in age to the study population (mean 6.1 years, range two to 15).
      Cronbach's alpha coefficient for the pre-operative assessment total score was
      0.84. The test-retest reliability coefficient for the total score was 0.98,
      indicating very high reproducibility. The 14-item Paediatric Throat Disorders
      Outcome Test discriminated well between children known to suffer with throat
      problems and a group of healthy controls (p < 0.0001; t = 24.016). Six months
      after surgical intervention, parentally reported questionnaire scores had
      improved (i.e. were lower) (p < 0.0001; t = 7.01). The standard effect size (i.e.
      change in mean divided by baseline standard deviation) for children for whom post
      operative questionnaires were completed was 1.53; this is very large.
      CONCLUSIONS: The 14-item Paediatric Throat Disorders Outcome Test is an
      appropriate, disease-specific, parent-reported outcome measure for children with
      throat disorders, for which we have demonstrated internal consistency,
      reliability, responsiveness to change and two forms of construct validity.

PMID- 20053314
TI  - Comparison of antioxidant defence parameters in colostrum and milk between
      Berrichon du Cher ewes and Uhrusk ewes.
AB  - The aim of the study was to evaluate the profile of antioxidant parameters in
      ewes' colostrum and milk in relation to breed during 5 d post partum. Total
      antioxidant capacity (TAC) was analysed and the activity of the enzymic
      antioxidants, glutathione peroxidase (GSH-Px) and glutathione transferase (GSH
      Tr), as well as the concentration of the non-enzymic antioxidants, vitamin C,
      vitamin A and beta-carotene, were measured. Samples were collected from healthy
      animals belonging to two ewe breeds: Berrichon du Cher (n=15) and Uhrusk (n=15)
      kept in the Podlasie Province (Poland). Colostrum was sampled directly after
      parturition, as well as after 12, 24 and 48 h later and milk was sampled 5 d
      after parturition. Colostrum and milk for the evaluation of all parameters except
      for vitamin A and beta-carotene were centrifuged, and the supernatant was used
      for further analysis. Spectrophotometric methods were used for biochemical
      measurements. The results showed dynamic changes of antioxidative parameters
      within the time period examined. TAC values and GSH-Px activity increased
      significantly during the experiment. GSH-Tr activity showed a similar tendency in
      Uhrusk ewes but an opposite relationship in Berrichon du Cher. Concentrations of
      examined vitamins followed the increasing trends noticed in the activities of
      antioxidative enzymes. Moreover, differences between breeds in the evaluated
      parameters were detected; these differences were not unequivocal however. The
      results are also a source of not previously published physiological antioxidant
      profile in colostrum and milk of ewes over the post-partum period.

PMID- 20053315
TI  - Growth inhibitory effects of casein hydrolysates on human cancer cell lines.
AB  - The aim of this study was to investigate the effects of unhydrolysed/intact
      casein and eight different sodium casein hydrolysates (a-h) on the viability and
      growth of human cancer cell lines. Both human Jurkat T cells and Caco-2 cells
      were incubated with increasing concentrations of the test compounds (0.5-10% v/v)
      for 24 h. Cell viability was assessed using the MTT, lactate dehydrogenase (LDH)
      release and Trypan Blue assays. Cell growth was monitored using the MTT, Trypan
      Blue and Bromodeoxyuridine (BrdU) proliferation assays. Casein hydrolysates b, c
      and f had an inhibitory effect on the viability and growth of both cell lines.
      The casein hydrolysates did not negatively affect the membrane integrity of both
      Jurkat and Caco-2 cells. In Jurkat cells hydrolysates a and h had an inhibitory
      effect on DNA synthesis after 24 h, while in Caco-2 cells DNA synthesis was not
      affected. In conclusion, we found that the different casein hydrolysates had cell
      specific effects which target particular functions within the cell. Overall,
      casein hydrolysates had no effect on membrane integrity while they had varied
      effects on mitochondrial activity and DNA synthesis in the different cell lines.

PMID- 20053316
TI  - Simultaneous pasteurization and homogenization of human milk by combining heat
      and ultrasound: effect on milk quality.
AB  - The combination of ultrasound and heat (thermoultrasound) is an emerging food
      preservation technique that retains higher quantities of bioactive components
      compared with current thermal pasteurization practice, but has not yet been
      assessed for pasteurizing human milk. Artificially contaminated human milk
      samples were treated with ultrasound (20 kHz, 150 watts) with and without
      heating. The retention of four human milk proteins was quantified by biochemical
      assay and laser scattering particle sizing was used to determine the extent of
      homogenization. While ultrasonic treatment was effective at inactivating
      Escherichia coli (D4 degrees C=5.94 min), Staphylococcus epidermidis exhibited
      resistance (D4 degrees C=16.01 min). Thermoultrasonic treatment was considerably
      more effective (Esch. coli D45 degrees C=1.74 min, D50 degrees C=0.89 min; Staph.
      epidermidis D45 degrees C=2.08 min, D50 degrees C=0.94 minutes) with a predicted
      retention (2.8 min treatment, 50 degrees C) of secretory IgA lysozyme,
      lactoferrin and bile salt stimulated lipase of 91, 80, 77, and 45%, respectively.
      Homogenization of the milk samples occurred after 5 min and 2 min of ultrasonic
      and thermoultrasonic treatment, respectively. Thermoultrasonic treatment is an
      effective method for pasteurizing donor human milk and retaining a greater
      proportion of bioactive components compared with current practices. However,
      further studies are required to assess the practicality of applying this
      technique routinely to donor human milk.

PMID- 20053317
TI  - Effects of acarbose on ruminal fermentation, blood metabolites and microbial
      profile involved in ruminal acidosis in lactating cows fed a high-carbohydrate
      ration.
AB  - The objective was to evaluate the effects of an inhibitor of alpha-amylase and
      glucosidase (acarbose, Pfizer Limited, Corby, UK) on ruminal fermentation, blood
      metabolism and microbial profile in dairy cows in a 2x2 cross-over experiment.
      Eight Holstein cows fitted with rumen cannulas (milk yield, 24.3+/-2.35 kg/d,
      body weight, 622+/-54 kg, days in milk, 183+/-67, 5 multiparous and 3
      primiparous) were used. Treatments were: control (no additive, CTR) and alpha
      amylase and glucosidase inhibitor (0.75 g acarbose-premix/cow per d, AMI).
      Animals were given ad-libitum access to a high non-fibre carbohydrate (NFC)
      partial mixed ration (PMR) containing 17.6% crude protein, 28.3% neutral
      detergent fibre, and 46.5% NFC in the dry matter and supplementary concentrate
      during milking. Blood samples were taken to determine blood glucose, insulin and
      urea within the first hour after the morning feeding on two separate days in each
      period. Samples of ruminal contents were collected during 3 d in each period at
      0, 4 and 8 h after feeding to determine volatile fatty acid and ammonia-N
      concentrations and to quantify protozoa, Streptococcus bovis and Megasphaera
      elsdenii. Rumen pH was recorded electronically at 22-min intervals during 6 d in
      each period. Results were analysed using a mixed-effects model. Cows on AMI
      treatment spent less time with ruminal pH <5.6 compared with cows in the CTR
      group (3.74 and 6.52+/-0.704 h/d, respectively). Cows in the AMI group had
      greater daily average pH compared with those in the CTR group (6.05 and 5.92+/
      0.042, respectively). AMI animals tended (P=0.09) to have lower Str. bovis to
      Meg. elsdenii ratio than CTR (4.09 and 26.8+/-12.0, respectively). These results
      indicate that dietary supplementation with acarbose in dairy cattle fed high
      production rations may be effective in reducing the time for which rumen pH is
      suboptimal, with no negative effects on ruminal fermentation and blood
      metabolites.

PMID- 20053318
TI  - Study on the combined effects of essential oils on microbiological quality of
      Fior di Latte cheese.
AB  - The effectiveness of three natural compounds in slowing down the deterioration of
      microbial quality of Fior di latte cheese is addressed. In particular, the
      control of the growth of spoilage microorganisms and the determination of the
      Microbiological Stability Limit (MAL) were the main goals. A Central Composite
      Design (CCD) strategy was adopted to highlight possible combined effects between
      three essential oils: sage and two types of lemon. Results showed an increase in
      the MAL value for all cheese samples packaged with the antimicrobial compounds,
      compared with the control cheese. Moreover, the combinations of the three
      essential oils indicated that the substances can act in a synergistic or
      antagonistic way, depending on their concentrations. In particular, a synergistic
      effect was evident when the three compounds were used at about 3000 ppm.

PMID- 20053319
TI  - Worldwide survey of published procedures to culture human embryonic stem cells.
AB  - Since their derivation 11 years ago, human embryonic stem (hES) cells have become
      a powerful tool in both basic biomedical research and developmental biology.
      Their capacity for self-renewal and differentiation into any tissue type has also
      brought interest from fields such as cell therapy and drug screening. We
      conducted an extensive analysis of 750 papers (51% of the total published about
      hES cells between 1998 and 2008) to present a spectrum of hES cell research
      including culture protocols developed worldwide. This review may stimulate
      discussions about the importance of having unvarying methods to culture hES
      cells, in order to facilitate comparisons among data obtained by research groups
      elsewhere, especially concerning preclinical studies. Moreover, the description
      of the most widely used cell lines, reagents, and procedures adopted
      internationally will help newcomers on deciding the best strategies for starting
      their own studies. Finally, the results will contribute with the efforts of stem
      cell researchers on comparing the performance of different aspects related to hES
      cell culture methods.

PMID- 20053320
TI  - Monitoring of intraportal liver cell application in children.
AB  - Despite recent advances and promising results in children, liver cell
      transplantation (LCT) should still be regarded as an experimental therapy.
      Several substantial complications are known from animal studies and individual
      patients. However, safety data on liver cell infusion in children are scarce. We
      used LCT in four children of different ages (3 weeks to 11 years, 3-40 kg) and
      underlying diseases [acute liver failure (n = 1), urea cycle disorders (n = 2),
      and Crigler-Najjar syndrome (n = 1)]. Vital parameters, portal vein flow (PVF),
      portal vein pressure (PVP), and liver enzymes were measured every 5 min during
      cell application and hourly thereafter between applications. An application
      protocol with discontinuation rules depending on changes in PVF and PVP was
      developed and successfully applied. Application was feasible in all children
      despite the catastrophic overall condition of the patient with acute liver
      failure. No application-related changes in vital parameters were found, and none
      of the children experienced clinical signs of portal vein thrombosis, pulmonary
      embolism, or anaphylactic reactions. Time courses for changes in PVF, PVP, and
      liver enzymes were obtained. Thorough monitoring of portal vein pressure and
      duplex sonography according to a defined protocol is likely to increase safety of
      cell application in pediatric LCT.

PMID- 20053322
TI  - Preface: real-world clinical experience with alefacept-the Amevive Wisdom
      Acquired from Real-World Evidence (AWARE) study.

PMID- 20053323
TI  - The AWARE study: methodology and baseline characteristics.
AB  - BACKGROUND: Alefacept was the first biologic therapy approved by Health Canada
      for the treatment of moderate to severe chronic plaque psoriasis and is used
      either alone or as part of combination therapy. OBJECTIVE: AWARE (Amevive Wisdom
      Acquired from Real-World Evidence) is a multicenter, observational phase IV
      Canadian study of psoriasis patients treated with alefacept. This study's main
      goals were to develop a shared, real-time, national clinical database to support
      best practice and optimize the care of patients receiving alefacept and to gain
      an understanding of how alefacept is used in Canadian clinical practice. Baseline
      patient demographic data are described herein. METHODS: Patients with chronic
      plaque psoriasis were enrolled from 37 clinics across Canada. Subjects received
      at least one course of alefacept treatment followed by a period of at least 12
      weeks off treatment and were prospectively followed for at least 60 weeks.
      Baseline assessments included patient demographics, relevant medical history,
      psoriasis and treatment history, reasons for initiating alefacept, enrolling
      physician's initial alefacept treatment plan and strategy, percent body surface
      area (BSA) involvement with psoriasis, and physician's baseline assessment of
      disease control. Subsequent assessments at each follow-up visit included the
      patient's response and the physician's assessment. RESULTS: A total of 426 adult
      patients with predominantly chronic plaque psoriasis, with or without other types
      of psoriasis, were enrolled into the AWARE registry. Patients generally had
      moderate to severe psoriasis, with more than half (55.8%) having little or no
      disease control at baseline as assessed by their clinician, and 77% had > 10% BSA
      involvement with psoriasis. All patients in the AWARE patient population were
      receiving one or more treatments for psoriasis prior to or at the time of
      enrolment, and the majority continued to receive concomitant treatments at the
      time of study enrolment. CONCLUSION: The AWARE registry enrolled a broad group of
      real-world patients with chronic plaque psoriasis treated with alefacept in
      clinical practices across Canada.

PMID- 20053324
TI  - Efficacy outcomes in patients using alefacept in the AWARE study.
AB  - BACKGROUND: Alefacept has demonstrated efficacy in clinical trials of patients
      with chronic plaque psoriasis, either as monotherapy or combined with other
      treatment modalities such as phototherapy. OBJECTIVE: AWARE (Amevive Wisdom
      Acquired from Real-World Evidence) is a multicenter, observational, phase IV
      Canadian registry of psoriasis patients treated with alefacept. METHODS: Patients
      with chronic plaque psoriasis were treated with at least one course of alefacept,
      either alone or added on to their existing antipsoriatic treatment regimen. Each
      course of alefacept was followed by a period of at least 12 weeks off treatment.
      Efficacy outcomes included physicians' and patients' assessments of response at
      week 18, as well as change in percent body surface area (BSA) involvement with
      psoriasis. The time to retreatment was assessed in patients receiving a second
      course of alefacept during at least 60 weeks of prospective follow-up. RESULTS:
      The majority of patients received alefacept in combination with other
      antipsoriatic therapies. Physicians' and patients' assessments of response at 18
      weeks showed that 42% and 41% of patients, respectively, had a "cleared to marked
      response" and a further 42% had a "moderate to some response." Among those
      patients whose psoriasis was moderately controlled or not controlled at baseline,
      49 to 51% and 33 to 36%, respectively, improved to "cleared to marked response"
      at 18 weeks. A substantial shift in percent BSA involvement with psoriasis was
      observed at 18 weeks, with 55% of patients having a BSA involvement of < 10% at
      week 18 compared to only 20% having this level of BSA involvement at baseline.
      The mean time to retreatment among the 60% of patients who received a second
      course of alefacept was 19.3 weeks (range 2-47 weeks). CONCLUSION: A single
      course of alefacept therapy improved outcomes in this broad population of real
      world chronic plaque psoriasis patients. STUDY LIMITATIONS: The limitations of
      this study include its nonrandomized, noncontrolled, noncomparative design, which
      allowed multiple different treatment approaches across all patients. The rating
      scales used in this study have not been previously validated, and ranges were
      assigned to baseline control and response data that are not specifically defined.
      Clinicians did not receive specific training in using these scales; therefore,
      interrater variability could not be assessed.

PMID- 20053325
TI  - Patterns of combination therapy with alefacept for the treatment of psoriasis in
      Canada in the AWARE study.
AB  - BACKGROUND: Evidence from clinical trials supports the use of alefacept for the
      treatment of patients with chronic plaque psoriasis, either as monotherapy or
      combined with other treatment modalities. OBJECTIVE: AWARE (Amevive Wisdom
      Acquired from Real-World Evidence) is a multicenter, observational, phase IV
      Canadian registry of psoriasis patients treated with alefacept. METHODS: Patients
      with chronic plaque psoriasis were treated with at least one course of alefacept
      treatment followed by a period of at least 12 weeks off-treatment. The use of
      combination therapy with alefacept in a real-world population of psoriasis
      patients is presented here, including the types of psoriasis therapies received
      by patients at the time of enrolment, reasons for initiating alefacept, and
      discontinuation or dosage reduction of concomitant therapy. RESULTS: The majority
      of patients were receiving other antipsoriatic therapies at the time of enrolment
      into the AWARE study, most commonly topical therapy, systemic agents, or
      phototherapy. Most patients were receiving monotherapy prior to the initiation of
      alefacept. There was little change in the use of topical therapies with alefacept
      at 24 weeks, whereas a substantial proportion of patients were able to reduce or
      discontinue concomitant systemic therapies and/or phototherapy. The use of
      combination therapy regimens was relatively consistent across the country and by
      age groups, although younger patients were prescribed systemic agents more often
      than older patients. CONCLUSION: Alefacept is commonly added to other
      antipsoriatic therapies in a broad population of real-world chronic plaque
      psoriasis patients in Canada and may allow for dosage reduction or
      discontinuation of concomitant systemic agents or phototherapy.

PMID- 20053326
TI  - Update on alefacept safety.
AB  - BACKGROUND: Alefacept has been demonstrated in clinical trials to be an
      effective, safe, and well-tolerated treatment strategy when used alone or in
      combination with other antipsoriatic therapies in patients with chronic plaque
      psoriasis. OBJECTIVE: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is
      a multicenter, observational, Canadian phase IV registry evaluating the efficacy
      and safety of alefacept, alone or in combination with other antipsoriatic
      therapies, in patients with psoriasis. METHODS: Patients with chronic plaque
      psoriasis were treated with at least one course of alefacept followed by an off
      treatment period, typically lasting 12 or more weeks. Prospective follow-up was
      at least 60 weeks, depending on when patients presented for retreatment. Safety
      data collected throughout the study included the incidence of serious adverse
      events (SAEs), dosing suspensions, and withdrawals owing to adverse events.
      RESULTS: Twelve SAEs were reported in psoriasis patients treated with at least
      one course of alefacept, with only one considered to be possibly related to the
      study drug. Approximately one-quarter of patients missed at least one dose of
      alefacept during the course of the study. A total of 291 doses of alefacept were
      missed, representing almost 4% of the total doses administered in this group of
      patients. Low CD4(+) count was the most frequent reason for missed doses;
      however, no patient had persistently low CD4(+) counts requiring permanent
      discontinuation of alefacept treatment. Seven patients in the AWARE registry
      discontinued treatment with alefacept, with the most common reason being patient
      request. CONCLUSION: The AWARE study supports the safety of alefacept used alone
      or in combination with other antipsoriatic therapies, in a broad population of
      real-world chronic plaque psoriasis patients in Canada.

PMID- 20053327
TI  - The next phase of real-world clinical experience with alefacept: the AWARE-2
      registry.

PMID- 20053328
TI  - Diagnostic tools in the indications for allogeneic stem cell transplantation in
      myelodysplastic syndromes.
AB  - The rates of allogeneic stem cell transplantation (SCT) to treat the
      myelodysplastic syndromes (MDS) is continually increasing. However, given the
      growing arsenal of therapeutic options in parallel to deeper insight into the
      heterogeneity of this disorder, determining the indications for SCT in MDS
      remains a difficult task. The International Prognostic Scoring System (IPSS)
      serves as a guideline for therapeutic decisions, but many aspects (eg,
      interpretation of rare cytogenetic abnormalities, combinations of chromosomal
      alterations and/or molecular markers, variant clinical courses within distinct
      biological subgroups) remain the subject of continuous investigation. In an
      effort to achieve a more well-differentiated risk categorization, attempts have
      been made to perform a more detailed cytogenetic categorization, and the use of
      various fluorescein in situ hybridization (FISH) techniques has improved the
      description of aberrations. Multicenter initiatives have standardized
      multiparameter flow cytometry techniques for diagnosis of MDS. In advanced MDS,
      screening for molecular mutations can identify cases with a high transformation
      risk. Finally, the new World Health Organization classification system provides a
      more homogenous morphological categorization of MDS compared with the former
      French-American-British system. Consequently, in the near future, risk
      stratification in MDS might incorporate additional diagnostic tools and
      categorization systems aimed at improving the timing and indication for SCT in
      this complex disorder.

PMID- 20053329
TI  - Impact of cyclosporine-A concentration on the incidence of severe acute graft
      versus-host disease after allogeneic stem cell transplantation.
AB  - This single-center retrospective study analyzed 85 consecutive patients who
      underwent allogeneic stem cell transplantation (allo-SCT) with the aim to assess
      whether there is a correlation between exposure to cyclosporine-A (CsA; as
      measured by CsA concentrations during the first month after allo-SCT) and the
      risk for developing severe grade III-IV acute graft-versus-host disease (aGVHD).
      The median concentrations of CsA in the blood at 1, 2, 3, and 4 weeks after allo
      SCT were 348 (range: 172-733), 284 (range: 137-535), 274 (range: 107-649), and
      247 (range: 37-695) ng/mL, respectively. Overall, grade II-IV aGVHD occurred in
      36 patients (42%) at a median of 29 (range: 6-100) days after allo-SCT. The
      incidence of grade III-IV aGVHD (n = 20) was 23% (95% confidence interval [CI],
      14%-32%). In univariate analysis, patients receiving allo-SCT from an HLA-matched
      unrelated donor had a higher risk of grade III-IV aGVHD, and patients having the
      lowest CsA concentration in the first and second weeks after allo-SCT had a
      significantly higher risk of grade III-IV aGVHD. In a multivariate logistic
      regression analysis, a higher CsA concentration measured during the first week
      following graft infusion was the strongest parameter significantly associated
      with a reduced risk of severe grade II-IV aGVHD (P = .012; relative risk [RR] =
      0.24; 95% CI, 0.08-0.73). Of note, when adjusted by donor type, CsA concentration
      in week 1 remained significantly associated with risk of severe grade II-IV aGVHD
      (P = .014). We conclude that precise monitoring of CsA concentrations and
      adjustment of CsA dose early after allo-SCT may be effective to prevent onset of
      severe aGVHD.

PMID- 20053330
TI  - A comparison of HLA-identical sibling allogeneic versus autologous
      transplantation for diffuse large B cell lymphoma: a report from the CIBMTR.
AB  - We compared outcomes of 916 diffuse large B cell lymphoma (DLBCL) patients aged
      >or=18 years undergoing first autologous (n = 837) or myeloablative (MA)
      allogeneic hematopoietic cell transplant (HCT) (n = 79) between 1995 and 2003
      reported to the Center for International Blood and Marrow Transplant Research
      (CIBMTR). Median follow-up was 81 months for allogeneic HCT versus 60 months for
      autologous HCT. Allogeneic HCT recipients were more likely to have high-risk
      disease features including higher stage, more prior chemotherapy regimens, and
      resistant disease. Allogeneic HCT was associated with a higher 1 year treatment
      related mortality (TRM) (relative risk [RR] 4.88, 95% confidence interval [CI],
      3.21-7.40, P < .001), treatment failure (RR 2.06, 95% CI, 1.54-2.75, P < .001),
      and mortality (RR 2.75, 95% CI, 2.03-3.72, P < .001). Risk of disease progression
      was similar in the 2 groups (RR 1.12, 95% CI, 0.73-1.72, P = .59). In fact, for 1
      year survivors, no significant differences were observed for TRM, progression,
      progression-free (PFS) or overall survival (OS). Increased risks of TRM and
      mortality were associated with older age (>50 years), lower performance score,
      chemoresistance, and earlier year of transplant. In a cohort of mainly high-risk
      DLBCL patients, upfront MA allogeneic HCT, although associated with increased
      early mortality, was associated with a similar risk of disease progression
      compared to lower risk patients receiving autologous HCT.

PMID- 20053331
TI  - Hepatic safety of voriconazole after allogeneic hematopoietic stem cell
      transplantation.
AB  - Voriconazole is increasingly used in allogeneic hematopoietic stem cell
      transplantation (HSCT) for prophylaxis and treatment of fungal infections.
      Hepatic dysfunction is common in patients undergoing HSCT and may have an impact
      on the clinical decision to institute voriconazole. We conducted a retrospective
      review of all adult and pediatric HSCT recipients who received >2 consecutive
      doses of voriconazole between January 2005 and February 2008. Clinical
      hepatotoxicity was defined as the subjective attribution of liver enzyme
      elevation (even a mild one) to hepatotoxicity because of voriconazole by the
      treating physician and leading to discontinuation of voriconazole. Biochemical
      hepatotoxicity was defined as an elevation in one or more liver enzymes to >3
      times the upper limit of normal or >3 times the baseline value if abnormal at
      baseline. Liver enzymes assessed included aspartate aminotransferase, alanine
      aminotransferase, alkaline phosphatase, and total bilirubin. Simple and multiple
      logistic regressions were used to define the risks for hepatic dysfunction. The
      Wilcoxon signed-rank test was used to assess the differences in liver function
      test values before, during, and after the use of voriconazole. Sixty-eight of 200
      patients (34%) developed hepatotoxicity while on voriconazole. The median
      duration of voriconazole therapy was 72 days (range, 1-804 days). Biochemical
      hepatotoxicity occurred in 51 patients (75%); clinical hepatotoxicity, in 17
      patients (25%). Thirty-five (51%) of the patients with hepatotoxicity required
      discontinuation of therapy. In simple logistic regression, acute graft-versus
      host disease (GVHD) was a risk factor for hepatotoxicity, and receipt of a T-cell
      depleted allograft was protective. In multiple logistic regression, acute GVHD (P
      = .002) remained significant. There were no cases of liver failure or death
      attributed to voriconazole. In this cohort of patients undergoing allogeneic
      HSCT, the rate of hepatotoxicity while on voriconazole was 34%. In general, the
      hepatic dysfunction was mild and reversible. Voriconazole therapy with monitoring
      appears to be reasonably safe for use in HSCT recipients at high risk for
      invasive fungal infections.

PMID- 20053332
TI  - Lung function and long-term complications after allogeneic hematopoietic cell
      transplant.
AB  - It is unknown if diminished pulmonary function early after allogeneic
      hematopoietic transplant is associated with poor long-term outcomes. The
      objective of this study was to determine if posttransplant lung function is
      associated with 5-year nonrelapse mortality (NRM) and the development of chronic
      graft-versus-host disease (cGVHD). Retrospective analysis was done for 2158
      patients who had routine pulmonary function testing 60-120 days after transplant
      between 1992 and 2004. Cox regression was used to assess the hazard ratio for 5
      year NRM. A second analysis assessed the hazard ratio for the development of
      cGVHD. Lung function score was the primary exposure, and was calculated according
      to forced expiratory volume in 1 second (FEV(1)) and carbon monoxide diffusion
      capapcity (DLCO). Individual pulmonary function parameters were secondary
      exposures. The primary outcomes were 5-year NRM and the development of cGVHD.
      Most patients had normal lung function following transplant. A higher lung
      function score, signifying greater impairment, was associated with an increased
      risk of mortality (category 1 hazard ratio [HR] 1.47 [1.17-1.85]; category 2 HR
      3.38 [2.53-4.53]; category 3 HR 7.80 [4.15-14.68]). A similar association was
      observed for all individual pulmonary function parameters. Low FEV(1) was
      associated with the subsequent development of cGVHD (FEV(1) 70%-79% HR 1.26 [1.01
      1.57]; 60%-69% HR 1.48 [1.10-2.01]; <60% HR 2.02 [1.34-3.05]). Models using
      either lung function score or individual pulmonary function parameters performed
      about equally well as judged by the C-statistic. Impaired lung function at day 80
      posttransplant was associated with a higher risk of NRM. A low FEV(1) following
      transplant was associated with developing cGVHD within 1 year.

PMID- 20053334
TI  - Fulminant myocarditis after allogeneic bone marrow transplantation: successful
      cytomegalovirus therapy and mechanical circulatory support for bridge to
      recovery.

PMID- 20053335
TI  - Chromosomally integrated human herpesvirus 6: transmission via cord blood-derived
      unrelated hematopoietic stem cell transplantation.

PMID- 20053336
TI  - CCR5 expression on cells from HLA-matched unrelated marrow donors and graft
      versus-host disease.

PMID- 20053337
TI  - Institution affects association between CMV seronegative graft and leukemic
      relapse after pediatric HCT.

PMID- 20053338
TI  - Alloimmune retinopathy associated with antibodies to transducin-alpha as a
      complication of chronic graft-versus-host disease.

PMID- 20053340
TI  - Feeding the hungry ghosts.

PMID- 20053341
TI  - Quiz page. CMV colitis presenting as a colonic mass.

PMID- 20053342
TI  - Coronary calcifications: lessons from histology in CKD patients.

PMID- 20053343
TI  - Risk factors for ESRD: lessons from a community study and implications for public
      health.

PMID- 20053344
TI  - A software upgrade: CKD testing in 2010.

PMID- 20053346
TI  - Alterations in regional homogeneity of resting-state brain activity in autism
      spectrum disorders.
AB  - Measures assessing resting-state brain activity with blood oxygen level dependent
      (BOLD) functional magnetic resonance imaging (fMRI) can reveal cognitive
      disorders at an early stage. Analysis of regional homogeneity (ReHo) measures the
      local synchronization of spontaneous fMRI signals and has been successfully
      utilized in detecting alterations in subjects with attention-deficit
      hyperactivity disorder (ADHD), depression, schizophrenia, Parkinson's disease and
      Alzheimer's dementia. Resting-state brain activity was investigated in 28
      adolescents with autism spectrum disorders (ASD) and 27 typically developing
      controls being imaged with BOLD fMRI and analyzed with the ReHo method. The
      hypothesis was that ReHo of resting-state brain activity would be different
      between ASD subjects and controls in brain areas previously shown to display
      functional alterations in stimulus or task based fMRI studies. Compared with the
      controls, the subjects with ASD had significantly decreased ReHo in right
      superior temporal sulcus region, right inferior and middle frontal gyri,
      bilateral cerebellar crus I, right insula and right postcentral gyrus.
      Significantly increased ReHo was discovered in right thalamus, left inferior
      frontal and anterior subcallosal gyrus and bilateral cerebellar lobule VIII. We
      conclude that subjects with ASD have right dominant ReHo alterations of resting
      state brain activity, i.e., areas known to exhibit abnormal stimulus or task
      related functionality. Our results demonstrate that there is potential in
      utilizing the ReHo method in fMRI analyses of ASD.

PMID- 20053345
TI  - 24S-hydroxycholesterol effects on lipid metabolism genes are modeled in traumatic
      brain injury.
AB  - Membrane damage during traumatic brain injury (TBI) alters the brain homeostasis
      of cholesterol and other lipids. Cholesterol 24S-hydroxylase (Cyp46) is a
      cholesterol metabolic enzyme that is increased after TBI. Here, we systematically
      examined the effects of the enzymatic product of Cyp46, 24S-hydroxycholesterol,
      on the cholesterol regulatory genes, SREBP-1 and 2, their posttranslational
      regulation, and their effects on gene transcription. 24S-hydroxycholesterol
      increased levels of SREBP-1 mRNA and full-length protein but did not change
      levels of cleaved SREBP-1, consistent with the role of 24-hydroxycholesterol as
      an LXR agonist. In contrast, 24S-hydroxycholesterol decreased levels of LXR
      independent SREBP-2 mRNA, full-length protein, and SREBP-2 active cleavage
      product. We examined the downstream effects of changes to these lipid regulatory
      factors by studying cholesterol and fatty acid synthesis genes. In neuroblastoma
      cells, 24S-hydroxycholesterol decreased mRNA levels of the cholesterol synthesis
      genes HMG CoA reductase, squalene synthase, and FPP synthase but did not alter
      levels of the mRNA of fatty acid synthesis genes acetyl CoA carboxylase or fatty
      acid synthase. After TBI, as after 24S-hydroxycholesterol treatment in vitro,
      SREBP-1 mRNA levels were increased while SREBP-2 mRNA levels were decreased. Also
      similar to the in vitro results with 24S-hydroxycholesterol, HMG CoA reductase
      and squalene synthase mRNA levels were significantly decreased. Fatty acid
      synthase mRNA levels were not altered but acetyl CoA carboxylase mRNA levels were
      significantly decreased. Thus, changes to transcription of cholesterol synthesis
      genes after TBI were consistent with increases in Cyp46 activity, but changes to
      fatty acid synthesis genes must be regulated by other mechanisms.

PMID- 20053347
TI  - Neural correlates of generating visual nouns and motor verbs in a minimal phrase
      context.
AB  - The neural basis underlying the generation of nouns and verbs is still not
      completely understood. In classical generation tasks, specific features of the
      produced words can hardly be controlled. Therefore, the observed neural
      correlates of noun and verb production cannot be directly related to differences
      in specific features of the generated words. The present study seeks to address
      this issue by using a "minimal-phrase context" to elicit the activation of
      specific nouns and verbs. With this context, the to-be-generated words were
      highly constrained, and thus their semantic and other features (visual/action
      relatedness, word frequency, cloze probability, etc.) are well controlled. Thus,
      the present paradigm combines the advantages of classical word generation tasks
      (i.e., active semantic processing) with the advantages of tasks that allow for a
      high control of the experimental stimuli, such as passive viewing, reading, or
      lexical decision tasks. In an fMRI study, 17 participants generated verbs with
      strong motor and nouns with strong visual associations. Both noun and verb
      generation, compared to a rhyme generation baseline, elicited stronger activation
      in perisylvian language areas of the temporal and parietal cortex. In addition,
      stronger activation for nouns was found in the right middle/inferior temporal
      cortex. This activation supports the claim that noun generation is mediated by
      visual processing areas. Stronger activation for verb generation was found in the
      left superior temporal gyrus. Since this area is involved in motion perception,
      the results suggest that perceptual representations of movements mediate the
      generation of action verbs.

PMID- 20053348
TI  - Osteopontin provides early proliferative drive and may be dependent upon aberrant
      c-myc signalling in murine intestinal tumours.
AB  - Osteopontin is thought to play an important role in tumour metastasis. In a
      previous expression profiling study of murine intestinal adenomas, we found that
      Opn was up-regulated. We also found beta-catenin binding motifs in the Opn
      promoter implying that, contrary to current beliefs, induction of Opn may occur
      during early tumourigenesis. We studied 59 murine intestinal adenomas for Opn
      expression and every tumour showed up-regulation compared to normal mucosa
      confirming early deregulation in these tumours. To determine whether Opn makes a
      functional contribution to tumourigenesis, Opn was knocked down in the murine
      colorectal cancer cell line CMT93. Inhibition of Opn expression resulted in
      decreased cell numbers. To determine the mechanism of Opn induction in these
      tumours, the Opn promoter was cloned and each of the putative beta-catenin
      binding motifs was mutated. No major change in Opn promoter activity was observed
      thereby excluding Opn as a direct beta-catenin target gene. However, mutation of
      one of two putative c-myc binding sites in the Opn promoter led to near complete
      loss of promoter activity whilst mutation of one of four PEA3 binding sites led
      to a 50% reduction in promoter activity. We conclude that Opn deregulation is an
      early event in intestinal tumourigenesis which may promote tumour development by
      altering either proliferation or apoptosis to increase tumour cell numbers. Opn
      expression in the intestine is dependent on c-myc binding sites in the promoter.
      Since c-myc is a known beta-catenin target gene, deregulation of Opn may be a
      secondary effect of aberrant Wnt signalling.

PMID- 20053349
TI  - The effect of the weak androgen oxandrolone on psychological and behavioral
      characteristics in growth hormone-treated girls with Turner syndrome.
AB  - The weak androgen oxandrolone (Ox) increases height gain in growth-hormone (GH)
      treated girls with Turner syndrome (TS), but may also give rise to virilizing
      side effects. To assess the effect of Ox, at a conventional and low dosage, on
      behavior, aggression, romantic and sexual interest, mood, and gender role in GH
      treated girls with TS, a randomized, placebo-controlled, double-blind study was
      conducted. 133 patients were treated with GH (1.33 mg/m(2)/d) from baseline,
      combined with placebo (Pl), Ox 0.03 mg/kg/d, or Ox 0.06 mg/kg/d from the age of
      eight, and with estrogens from the age of 12. The child behavior checklist
      (CBCL), Junior Dutch Personality Questionnaire (DPQ-J), State-subscale of the
      Spielberger's State-Trait Anger Scale, Romantic and Sexual Interest
      Questionnaire, Mood Questionnaire, and Gender Role Questionnaire were filled out
      before, during, and after discontinuing Ox/Pl. The changes during Ox/Pl therapy
      were not significantly different between the dosage groups. In untreated
      patients, the mean CBCL total (P=0.002) and internalizing (P=0.003) T scores, as
      well as the mean DPQ-J social inadequacy SD score (SDS) (P=0.004) were higher
      than in reference girls, but decreased during GH+Ox/Pl therapy (P<0.001, P=0.05,
      P<0.001, respectively). Whereas the mean total (P=0.01) and internalizing
      (P<0.001) T score remained relatively high, the mean social inadequacy SDS became
      comparable with reference values. We conclude that in GH-treated girls with TS,
      Ox 0.03 mg/kg/d or 0.06 mg/kg/d does not cause evident psychological virilizing
      side effects. Problem behavior, frequently present in untreated girls with TS,
      decreases during therapy, but total and internalizing problem behavior remain
      increased.

PMID- 20053350
TI  - Effects of genistein in the maternal diet on reproductive development and spatial
      learning in male rats.
AB  - Endocrine disruptors, chemicals that disturb the actions of endogenous hormones,
      have been implicated in birth defects associated with hormone-dependent
      development. Phytoestrogens are a class of endocrine disruptors found in plants.
      In the current study we examined the effects of exposure at various perinatal
      time periods to genistein, a soy phytoestrogen, on reproductive development and
      learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food
      during both gestation and lactation, during gestation only, during lactation
      only, or during neither period. Measures of reproductive development and body
      mass were taken in the male offspring during postnatal development, and learning
      and memory performance was assessed in adulthood. Genistein exposure via the
      maternal diet decreased body mass in the male offspring of dams fed genistein
      during both gestation and lactation, during lactation only, but not during
      gestation only. Genistein decreased anogenital distance when exposure was during
      both gestation and lactation, but there was no effect when exposure was limited
      to one of these time periods. Similarly, spatial learning in the Morris water
      maze was impaired in male rats exposed to genistein during both gestation and
      lactation, but not in rats exposed during only one of these time periods. There
      was no effect of genistein on cued or contextual fear conditioning. In summary,
      the data indicate that exposure to genistein through the maternal diet
      significantly impacts growth in male offspring if exposure is during lactation.
      The effects of genistein on reproductive development and spatial learning
      required exposure throughout the pre- and postnatal periods.

PMID- 20053352
TI  - Assembly of a 20-nm protein cage by Escherichia coli 2-hydroxypentadienoic acid
      hydratase.
AB  - The pentameric Escherichia coli enzyme 2-hydroxypentadienoic acid hydratase
      assembles to form a 20-nm-diameter particle comprising 60 protein subunits,
      arranged with 532 symmetry when crystallised at low pH in the presence of
      phosphate or sulphate ions. The particles form rapidly and are stable in solution
      during gel filtration at low pH. They are probably formed through trimers of
      pentamers, which are stabilised by the interaction of two phosphate ions with
      residues of the N-terminal domains of subunits at the 3-fold axis. Once the
      particles are formed at high concentrations of phosphate (or sulphate), they
      remain stable in solution at 20-fold lower concentrations of the anion. Guest
      molecules can be trapped within the hollow protein shell during assembly. The C
      termini of the subunits are freely accessible on the surface of the protein cage
      and thus are ideal sites for addition of affinity tags or other modifications.
      These particles offer a convenient model system for studying the assembly of
      large symmetrical structures and a novel protein nanoparticle for encapsulation
      and cargo delivery.

PMID- 20053351
TI  - Myofilament length dependent activation.
AB  - The Frank-Starling law of the heart describes the interrelationship between end
      diastolic volume and cardiac ejection volume, a regulatory system that operates
      on a beat-to-beat basis. The main cellular mechanism that underlies this
      phenomenon is an increase in the responsiveness of cardiac myofilaments to
      activating Ca(2+) ions at a longer sarcomere length, commonly referred to as
      myofilament length-dependent activation. This review focuses on what molecular
      mechanisms may underlie myofilament length dependency. Specifically, the roles of
      inter-filament spacing, thick and thin filament based regulation, as well as
      sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of
      the heart" constitutes a fundamental cardiac property that has been appreciated
      for well over a century, it is still not known in muscle how the contractile
      apparatus transduces the information concerning sarcomere length to modulate
      ventricular pressure development.

PMID- 20053353
TI  - Model-guided mutagenesis drives functional studies of human NHA2, implicated in
      hypertension.
AB  - Human NHA2 is a poorly characterized Na(+)/H(+) antiporter recently implicated in
      essential hypertension. We used a range of computational tools and evolutionary
      conservation analysis to build and validate a three-dimensional model of NHA2
      based on the crystal structure of a distantly related bacterial transporter,
      NhaA. The model guided mutagenic evaluation of transport function, ion
      selectivity, and pH dependence of NHA2 by phenotype screening in yeast. We
      describe a cluster of essential, highly conserved titratable residues located in
      an assembly region made of two discontinuous helices of inverted topology, each
      interrupted by an extended chain. Whereas in NhaA, oppositely charged residues
      compensate for partial dipoles generated within this assembly, in NHA2, polar but
      uncharged residues suffice. Our findings led to a model for transport mechanism
      that was compared to the well-known electroneutral NHE1 and electrogenic NhaA
      subtypes. This study establishes NHA2 as a prototype for the poorly understood,
      yet ubiquitous, CPA2 antiporter family recently recognized in plants and
      metazoans and illustrates a structure-driven approach to derive functional
      information on a newly discovered transporter.

PMID- 20053354
TI  - Glycine-rich loop of mitochondrial processing peptidase alpha-subunit is
      responsible for substrate recognition by a mechanism analogous to mitochondrial
      receptor Tom20.
AB  - Tryptophan fluorescence measurements were used to characterize the local dynamics
      of the highly conserved glycine-rich loop (GRL) of the mitochondrial processing
      peptidase (MPP) alpha-subunit in the presence of the substrate precursor.
      Reporter tryptophan residue was introduced into the GRL of the yeast alpha-MPP
      (Y299W) or at a proximal site (Y303W). Time-resolved and steady-state
      fluorescence spectroscopy demonstrated that for Trp299, the primary contact with
      the yeast malate dehydrogenase precursor evokes a change of the local GRL
      mobility. Moreover, time-resolved measurements showed that a functionless alpha
      MPP with a single-residue deletion in the loop (Y303W/DeltaG292) is defective
      particularly in the primary contact with substrate. Thus, the GRL was proved to
      be part of a contact site of the enzyme specifically recognizing the substrate.
      Regarding the surface exposure and presence of the hydrophobic patches within the
      GRL, we proposed a functional analogy between the presequence recognition by the
      hydrophobic binding groove of the Tom20 mitochondrial import receptor and the GRL
      of the alpha-MPP. A molecular dynamics (MD) simulation of the MPP-substrate
      peptide complex model was employed to test this hypothesis. The initial
      positioning and conformation of the substrate peptide in the model fitting were
      chosen based on the analogy of its interaction with the Tom20 binding groove. MD
      simulation confirmed the stability of the proposed interaction and showed also a
      decrease in GRL flexibility in the presence of substrate, in agreement with
      fluorescence measurements. Moreover, conserved substrate hydrophobic residues in
      positions +1 and -4 to the cleavage site remain in close contact with the side
      chains of the GRL during the entire production part of MD simulation as
      stabilizing points of the hydrophobic interaction. We conclude that the GRL of
      the MPP alpha-subunit is the crucial evolutional outcome of the presequence
      recognition by MPP and represents a functional parallel with Tom20 import
      receptor.

PMID- 20053355
TI  - Rapid structural characterization of human antibody-antigen complexes through
      experimentally validated computational docking.
AB  - If we understand the structural rules governing antibody (Ab)-antigen (Ag)
      interactions in a given virus, then we have the molecular basis to attempt to
      design and synthesize new epitopes to be used as vaccines or optimize the
      antibodies themselves for passive immunization. Comparing the binding of several
      different antibodies to related Ags should also further our understanding of
      general principles of recognition. To obtain and compare the three-dimensional
      structure of a large number of different complexes, however, we need a faster
      method than traditional experimental techniques. While biocomputational docking
      is fast, its results might not be accurate. Combining experimental validation
      with computational prediction may be a solution. As a proof of concept, here we
      isolated a monoclonal Ab from the blood of a human donor recovered from dengue
      virus infection, characterized its immunological properties, and identified its
      epitope on domain III of dengue virus E protein through simple and rapid NMR
      chemical shift mapping experiments. We then obtained the three-dimensional
      structure of the Ab/Ag complex by computational docking, using the NMR data to
      drive and validate the results. In an attempt to represent the multiple
      conformations available to flexible Ab loops, we docked several different
      starting models and present the result as an ensemble of models equally agreeing
      with the experimental data. The Ab was shown to bind a region accessible only in
      part on the viral surface, explaining why it cannot effectively neutralize the
      virus.

PMID- 20053356
TI  - Sequence recognition of DNA by protein-induced conformational transitions.
AB  - The binding of proteins to specific sequences of DNA is an important feature of
      virtually all DNA transactions. Proteins recognize specific DNA sequences using
      both direct readout (sensing types and positions of DNA functional groups) and
      indirect readout (sensing DNA conformation and deformability). Previously we
      showed that the P22 c2 repressor N-terminal domain (P22R NTD) forces the central
      non-contacted 5'-ATAT-3' sequence of the DNA operator into the B' state, a state
      known to affect DNA hydration, rigidity and bending. Usually the B' state, with a
      narrow minor groove and a spine of hydration, is reserved for A-tract DNA (TpA
      steps disrupt A-tracts). Here, we have co-crystallized P22R NTD with an operator
      containing a central 5'-ACGT-3' sequence in the non-contacted region. C.G base
      pairs have not previously been observed in the B' state and are thought to
      prevent it. However, P22R NTD induces a narrow minor groove and a spine of
      hydration to 5'-ACGT-3'. We observe that C.G base pairs have distinctive
      destabilizing and disordering effects on the spine of hydration. It appears that
      the reduced stability of the spine results in a higher energy cost for the B to
      B' transition. The differential effect of DNA sequence on the barrier to this
      transition allows the protein to sense the non-contacted DNA sequence.

PMID- 20053357
TI  - The dimeric structure and the bivalent recognition of H3K4me3 by the tumor
      suppressor ING4 suggests a mechanism for enhanced targeting of the HBO1 complex
      to chromatin.
AB  - The INhibitor of Growth (ING) family of tumor suppressors regulates the
      transcriptional state of chromatin by recruiting remodeling complexes to sites
      with histone H3 trimethylated at position K4 (H3K4me3). This modification is
      recognized by the plant homeodomain (PHD) present at the C-terminus in the five
      members of the ING family. ING4 facilitates histone H3 acetylation by the HBO1
      complex. Here, we show that ING4 forms homodimers through its N-terminal domain,
      which folds independently into an elongated coiled-coil structure. The central
      region of ING4, which contains the nuclear localization sequence, is disordered
      and flexible and does not directly interact with p53, or does it with very low
      affinity, in contrast to previous findings. The NMR analysis of the full-length
      protein reveals that the two PHD fingers of the dimer are chemically equivalent
      and independent of the rest of the molecule. The detailed NMR analysis of the
      full-length dimeric protein binding to histone H3K4me3 shows essentially the same
      binding site and affinity as the isolated PHD finger. Therefore, the ING4 dimer
      has two identical and independent binding sites for H3K4me3 tails, which, in the
      context of the chromatin, could belong to the same or to different nucleosomes.
      These results show that ING4 is a bivalent reader of the chromatin H3K4me3
      modification and suggest a mechanism for enhanced targeting of the HBO1 complex
      to specific chromatin sites. This mechanism could be common to other ING
      containing remodeling complexes.

PMID- 20053358
TI  - Structure, dynamics, and RNA interaction analysis of the human SBDS protein.
AB  - Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with
      pleiotropic phenotypes, including pancreatic deficiencies, bone marrow
      dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal
      abnormalities. This syndrome has been associated with mutations in the SBDS gene,
      which encodes a conserved protein showing orthologs in Archaea and eukaryotes.
      The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication
      of different cell type requirements for a fully functional SBDS protein. RNA
      binding activity has been predicted for archaeal and yeast SBDS orthologs, with
      the latter also being implicated in ribosome biogenesis. However, full-length
      SBDS orthologs function in a species-specific manner, indicating that the
      knowledge obtained from model systems may be of limited use in understanding
      major unresolved issues regarding SBDS function, namely, the effect of mutations
      in human SBDS on its biochemical function and the specificity of RNA interaction.
      We determined the solution structure and backbone dynamics of the human SBDS
      protein and describe its RNA binding site using NMR spectroscopy. Similarly to
      the crystal structures of Archaea, the overall structure of human SBDS comprises
      three well-folded domains. However, significant conformational exchange was
      observed in NMR dynamics experiments for the flexible linker between the N
      terminal domain and the central domain, and these experiments also reflect the
      relative motions of the domains. RNA titrations monitored by heteronuclear
      correlation experiments and chemical shift mapping analysis identified a classic
      RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that
      concentrates most of the mutations described for the human SBDS.

PMID- 20053359
TI  - Conformational dynamics and structural plasticity play critical roles in the
      ubiquitin recognition of a UIM domain.
AB  - Ubiquitin-interacting motifs (UIMs) are an important class of protein domains
      that interact with ubiquitin or ubiquitin-like proteins. These approximately 20
      residue-long domains are found in a variety of ubiquitin receptor proteins and
      serve as recognition modules towards intracellular targets, which may be
      individual ubiquitin subunits or polyubiquitin chains attached to a variety of
      proteins. Previous structural studies of interactions between UIMs and ubiquitin
      have shown that UIMs adopt an extended structure of a single alpha-helix,
      containing a hydrophobic surface with a conserved sequence pattern that interacts
      with key hydrophobic residues on ubiquitin. In light of this large body of
      structural studies, details regarding the presence and the roles of structural
      dynamics and plasticity are surprisingly lacking. In order to better understand
      the structural basis of ubiquitin-UIM recognition, we have characterized changes
      in the structure and dynamics of ubiquitin upon binding of a UIM domain from the
      yeast Vps27 protein. The solution structure of a ubiquitin-UIM fusion protein
      designed to study these interactions is reported here and found to consist of a
      well-defined ubiquitin core and a bipartite UIM helix. Moreover, we have studied
      the plasticity of the docking interface, as well as global changes in ubiquitin
      due to UIM binding at the picoseconds-to-nanoseconds and microseconds-to
      milliseconds protein motions by nuclear magnetic resonance relaxation. Changes in
      generalized-order parameters of amide groups show a distinct trend towards
      increased structural rigidity at the UIM-ubiquitin interface relative to values
      determined in unbound ubiquitin. Analysis of (15)N Carr-Purcell-Meiboom-Gill
      relaxation dispersion measurements suggests the presence of two types of motions:
      one directly related to the UIM-binding interface and the other induced to distal
      parts of the protein. This study demonstrates a case where localized interactions
      among protein domains have global effects on protein motions at timescales
      ranging from picoseconds to milliseconds.

PMID- 20053361
TI  - Desolvation and development of specific hydrophobic core packing during Im7
      folding.
AB  - Development of a tightly packed hydrophobic core drives the folding of water
      soluble globular proteins and is a key determinant of protein stability. Despite
      this, there remains much to be learnt about how and when the hydrophobic core
      becomes desolvated and tightly packed during protein folding. We have used the
      bacterial immunity protein Im7 to examine the specificity of hydrophobic core
      packing during folding. This small, four-helix protein has previously been shown
      to fold via a compact three-helical intermediate state. Here, overpacking
      substitutions, in which residue side-chain size is increased, were used to
      examine the specificity and malleability of core packing in the folding
      intermediate and rate-limiting transition state. In parallel, polar groups were
      introduced into the Im7 hydrophobic core via Val-->Thr or Phe-->Tyr substitutions
      and used to determine the solvation status of core residues at different stages
      of folding. Over 30 Im7 variants were created allowing both series of
      substitutions to cover all regions of the protein structure. Phi-value analysis
      demonstrated that the major changes in Im7 core solvation occur prior to the
      population of the folding intermediate, with key regions involved in docking of
      the short helix III remaining solvent-exposed until after the rate-limiting
      transition state has been traversed. In contrast, overpacking core residues
      revealed that some regions of the native Im7 core are remarkably malleable to
      increases in side-chain volume. Overpacking residues in other regions of the Im7
      core result in substantial (>2.5 kJ mol(-1)) destabilisation of the native
      structure or even prevents efficient folding to the native state. This study
      provides new insights into Im7 folding; demonstrating that whilst desolvation
      occurs early during folding, adoption of a specifically packed core is achieved
      only at the very last step in the folding mechanism.

PMID- 20053362
TI  - Lymphatic circulation of the rat cremaster muscle flap.

PMID- 20053360
TI  - The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR
      and X-ray crystallography.
AB  - Structure-based drug design is underway to inhibit the S100B-p53 interaction as a
      strategy for treating malignant melanoma. X-ray crystallography was used here to
      characterize an interaction between Ca(2)(+)-S100B and TRTK-12, a target that
      binds to the p53-binding site on S100B. The structures of Ca(2+)-S100B (1.5-A
      resolution) and S100B-Ca(2)(+)-TRTK-12 (2.0-A resolution) determined here
      indicate that the S100B-Ca(2+)-TRTK-12 complex is dominated by an interaction
      between Trp7 of TRTK-12 and a hydrophobic binding pocket exposed on Ca(2+)-S100B
      involving residues in helices 2 and 3 and loop 2. As with an S100B-Ca(2)(+)-p53
      peptide complex, TRTK-12 binding to Ca(2+)-S100B was found to increase the
      protein's Ca(2)(+)-binding affinity. One explanation for this effect was that
      peptide binding introduced a structural change that increased the number of
      Ca(2+) ligands and/or improved the Ca(2+) coordination geometry of S100B. This
      possibility was ruled out when the structures of S100B-Ca(2+)-TRTK-12 and S100B
      Ca(2+) were compared and calcium ion coordination by the protein was found to be
      nearly identical in both EF-hand calcium-binding domains (RMSD=0.19). On the
      other hand, B-factors for residues in EF2 of Ca(2+)-S100B were found to be
      significantly lowered with TRTK-12 bound. This result is consistent with NMR
      (15)N relaxation studies that showed that TRTK-12 binding eliminated dynamic
      properties observed in Ca(2+)-S100B. Such a loss of protein motion may also
      provide an explanation for how calcium-ion-binding affinity is increased upon
      binding a target. Lastly, it follows that any small-molecule inhibitor bound to
      Ca(2+)-S100B would also have to cause an increase in calcium-ion-binding affinity
      to be effective therapeutically inside a cell, so these data need to be
      considered in future drug design studies involving S100B.

PMID- 20053363
TI  - Quantitative distribution and colocalization of non-muscle myosin light chain
      kinase isoforms and cortactin in human lung endothelium.
AB  - Vascular barrier regulation is intimately linked to alterations in the
      distribution and configuration of the endothelial cell (EC) cytoskeleton in
      response to angiogenic and edemagenic agonists. Critical actin cytoskeletal
      rearrangement includes spatially directed increases in myosin light chain (MLC)
      phosphorylation, catalyzed by Ca(2+)/calmodulin-dependent non-muscle myosin light
      chain kinase variants (nmMLCK1- and -2), as well as association of nmMLCK with
      the actin-binding protein, cortactin. As these associations have proven difficult
      to quantify in a spatially specific manner, we now describe the utility of
      intensity correlation image analysis and the intensity correlation quotient (ICQ)
      to quantify colocalization in fixed and live cell imaging assays in human
      pulmonary artery EC. From baseline ICQ values averaging 0.216 reflecting
      colocalization of cortactin-DsRed with EGFP-nmMLCK fusion proteins in resting EC,
      thrombin-induced EC contraction significantly reduced cortactin-DsRed-EGFP-nmMLCK
      colocalization (nmMLCK1: ICQ=0.118; nmMLCK2: ICQ=0.091) whereas the potent EC
      barrier-protective agonist, sphingosine 1-phosphate (S1P), significantly
      increased nmMLCK-cortactin colocalization within lamellipodia (nmMLCK1:
      ICQ=0.275; nmMLCK2: ICQ=0.334). Over-expression of a cortactin-DsRed mutant
      fusion protein lacking the SH3 domain, known to be essential for cortactin-nmMLCK
      association, reduced baseline and S1P-mediated live cell colocalization with each
      nmMLCK variant (nmMLCK1: ICQ=0.160; nmMLCK2: ICQ=0.157). Similarly, expression of
      a truncated EGFP-nmMLCK2 mutant lacking cortactin- and actin-binding domains,
      markedly reduced basal localization in lamellipodia and abolished colocalization
      with cortactin-DsRed in lamellipodia after S1P (ICQ=-0.148). These data provide
      insights into the molecular basis for vascular barrier-regulatory cytoskeletal
      responses and support the utility of sophisticated imaging analyses and
      methodological assessment to quantify the critical nmMLCK and cortactin
      interaction during vascular barrier regulation.

PMID- 20053364
TI  - Endothelial progenitor cells in vascular health: focus on lifestyle.
AB  - Endothelial dysfunction, which is considered the functional equivalent of a
      disrupted balance between endothelial injury and repair, precedes overt
      atherosclerosis by many years. Although this phenomenon is part of the normal
      aging process, prevention of early and progressive endothelial dysfunction has
      become an important therapeutic target. Evidence has accumulated to show that
      endothelial progenitor cells (EPC), contribute substantially to preservation of a
      structurally and functionally intact endothelium. There has been considerable
      progress in our understanding of the various cell types that were in the past all
      covered by the term "EPC." EPC home to sites of endothelial injury and ischemia,
      where they proliferate, differentiate and integrate into the endothelial layer or
      exert a paracrine function by producing vascular growth factors. Although more
      emphasis has been put on the pharmacological approach of endothelial dysfunction,
      the effect of a healthy lifestyle, via mobilization and functional improvement of
      EPC, is increasingly recognized. This review will focus on successful lifestyle
      interventions that aim to maintain vascular health through beneficial actions on
      cell populations with vasculogenic potential ("EPC"). The role of physical
      activity and dietary recommendations, which are considered essential elements of
      a healthy lifestyle, will be particularly emphasized. A thorough understanding of
      the physiology of endothelial benefits, derived from such interventions, may help
      to implement these measures on top of classical drug therapy, but also provides a
      solid basis for primary prevention. The effects of additional elements of a
      comprehensive lifestyle advice, such as smoking cessation, weight and stress
      reduction, also comprise a modulation of EPC function and circulating numbers and
      are therefore included in this review as well.

PMID- 20053365
TI  - Microvascular retinal changes in patients presenting with acute coronary
      syndromes.
AB  - BACKGROUND: Retinal microvascular changes predict cardiovascular morbidity and
      mortality independent of classical risk factors. However, it is unclear which
      retinal changes characterize patients with established coronary artery disease
      (CAD), and in particular, with acute coronary syndromes (ACS). The aim of the
      present preliminary study was to assess retinopathy in these patients. METHODS:
      43 consecutive patients with ACS and 19 consecutive patients with stable CAD were
      investigated. Among the patient group with ACS, 20 patients presented with ST
      Elevation Myocardial Infarction (STEMI) and 23 patients presented with Non-STEMI
      (NSTEMI). Standardized protocols were used and retinal fundus photography was
      taken within 48 h post-coronary angiography to assess retinopathy and general
      arteriolar narrowing as arterio-venous ratio (AVR). Clinical and laboratory
      cardiovascular risk factors were recorded. RESULTS: Despite comparable age and
      comparable frequency of diabetes and hypertension, patients with ACS had a much
      higher likelihood for retinal microaneurysms and dot bleedings than patients with
      stable CAD (17 (40%) vs. 1 (5%) patients, OR 11.77; 95%CI 1.43-96.59; p=0.006).
      Performing multivariate analysis, this association remains significant (OR 20.5,
      95%CI 1.6-255, p=0.019). CAD patients presented more often with focal signs of
      arteriovenous nicking / focal vasoconstriction (10 (53%) vs. 9 (21%) patients, OR
      4.2; 95%CI 1.31-13.4; p=0.018), however after multivariate analysis this
      association lost significance. The AVR was comparably low in both groups.
      CONCLUSION: Patients with ACS present more often with dot bleedings and
      microaneurysms. These findings provide preliminary evidence that retinal fundus
      examination may be useful to contribute to the risk profile of patients, enabling
      a more intensive survey and care.

PMID- 20053366
TI  - Collagen glycation alters neovascularization in vitro and in vivo.
AB  - Microvascular network formation is required for the success of many therapies in
      regenerative medicine. The process of vessel assembly is fundamentally altered,
      however, in many people within the potential patient population, including the
      elderly and people with diabetes. Significant research has been performed to
      determine how cellular dysfunction contributes to this inadequate
      neovascularization, but alterations in the extracellular matrix (ECM) may also
      influence this process. Glycation of ECM proteins, specifically type I collagen,
      increases as people age and is accelerated due to uncontrolled diabetes. This
      glycation results in increased ECM stiffness and resistance to degradation. The
      goal of this research is to determine whether collagen glycation consistent with
      changes in aged (defined as people older than 80 years old) and diabetic
      individuals influences neovascularization. Collagen gels that were incubated in
      glucose-6-phopshate (G6P) for varying times exhibited cross-linking (26.2+/-8.1%
      and 31.3+/-5.6% for incubation in 375 mM G6P for 5 and 8 days, respectively),
      autofluorescence, and advanced glycation end product levels (666+/-481 and 2122+/
      501 pmol/mg protein for 5 and 8 days of 375 mM G6P, respectively) consistent with
      aged and diabetic populations. Three-dimensional culture models showed that
      sprouting angiogenesis was delayed in collagen gels with high levels of
      glycation. When implanted in vivo, glycated gels were degraded (44.4+/-4.2% and
      49.5+/-11.7% nondegraded gel remaining for gels incubated for 5 and 8 days in 375
      mM G6P, respectively) and vascularized (75.5+/-32.0 and 73.7+/-23.6
      vessels/mm(2)) more slowly than controls (22.3+/-9.9% gel remaining and 133.3+/
      31.0 vessels/mm(2)). These results suggest that glycation of collagen can alter
      neovascularization and may contribute to alterations in vessel assembly observed
      as people age and due to diabetes.

PMID- 20053367
TI  - Quantitative assessment of conjunctival microvascular circulation of the human
      eye.
AB  - Accessibility to the bulbar conjunctival microvasculature provides a means to
      assess blood supply to the cerebral cortex and thus optimize therapeutic
      interventions designed to prevent or reduce the risk of cerebral vascular disease
      and stroke. The feasibility of a method for quantitative measurements of
      conjunctiva blood vessel diameter, blood velocity, and flow in the human eye is
      reported. The method is based on slit lamp biomicroscope digital imaging coupled
      with a space time image analysis technique. A sequence of conjunctiva
      microvasculature images was captured at a rate of 50 Hz. The images were analyzed
      to determine blood vessel diameter, velocity and flow. Blood vessel diameter
      measurements ranged between 8.7 and 24.3 microns, with a mean value of 15.5
      microns. Blood flow rate ranged between 27.3 and 296.9 pl/s, with a mean value of
      111.8 pl/s. The relationship between blood flow and vessel diameter was fit with
      a power law curve (R=0.87). The application of this technique for in vivo
      quantitative assessment of blood flow dynamics has potential to impact diagnosis
      and monitoring of various cardiovascular and blood disorders.

PMID- 20053368
TI  - Role of the microenvironment in the specification of endothelial progenitors
      derived from embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells capable of differentiating in all
      the cell types present in a living organism. They derive from the inner cell mass
      of blastocysts of different species including humans. Given their unlimited
      potential, ES cells represent an invaluable resource of different cell types for
      transplantation and tissue engineering applications. However, in order to
      accomplish these therapeutic purposes, efficient and controlled in vitro systems
      of directing ES cell differentiation are mandatory. ES cell differentiation is
      strongly influenced by physical, chemical and cellular signals provided by the
      local microenvironment. Understanding the relationships occurring between
      differentiating cells and surrounding environment is pivotal for a successful ES
      cells-based therapy. This review describes three different methods of in vitro
      differentiation of ES cells by outlining the environmental elements required for
      endothelial fate specification. For each system, the efficiency of endothelial
      differentiation, the accessibility and the advantages are discussed. The main
      conclusion that arises from this analysis is that the knowledge of the role
      played by microenvironment in cell fate determination is essential to control and
      take advantage of ES cells potential.

PMID- 20053369
TI  - Streptozotocin induced activation of oxidative stress responsive splenic cell
      signaling pathways: protective role of arjunolic acid.
AB  - Present study investigates the beneficial role of arjunolic acid (AA) against the
      alteration in the cytokine levels and simultaneous activation of oxidative stress
      responsive signaling pathways in spleen under hyperglycemic condition. Diabetes
      was induced by injection of streptozotocin (STZ) (at a dose of 70 mg/kg body
      weight, injected in the tail vain). STZ administration elevated the levels of IL
      2 as well as IFN-gamma and attenuated the level of TNF-alpha in the sera of
      diabetic animals. In addition, hyperglycemia is also associated with the
      increased production of intracellular reactive intermediates resulting with the
      elevation in lipid peroxidation, protein carbonylation and reduction in
      intracellular antioxidant defense. Investigating the oxidative stress responsive
      cell signaling pathways, increased expressions (immunoreactive concentrations) of
      phosphorylated p65 as well as its inhibitor protein phospho IkappaBalpha and
      phosphorylated mitogen activated protein kinases (MAPKs) have been observed in
      diabetic spleen tissue. Studies on isolated splenocytes revealed that
      hyperglycemia caused disruption of mitochondrial membrane potential, elevation in
      the concentration of cytosolic cytochrome c as well as activation of caspase 3
      leading to apoptotic cell death. Histological examination revealed that diabetic
      induction depleted the white pulp scoring which is in agreement with the reduced
      immunological response. Treatment with AA prevented the hyperglycemia and its
      associated pathogenesis in spleen tissue. Results suggest that AA might act as an
      anti-diabetic and immunomodulatory agent against hyperglycemia.

PMID- 20053370
TI  - National trends in self-reported physical activity and sedentary behaviors among
      pregnant women: NHANES 1999-2006.
AB  - OBJECTIVE: The aims of this study were to describe the prevalence, trends, and
      correlates of physical activity among a national sample of pregnant women.
      METHOD: Using data collected from the 1999-2006 National Health and Nutrition
      Examination Survey, physical activity and sedentary behaviors were collected
      during interviews with 1280 pregnant women >/=16 years. Estimates were weighted
      to reflect the United States population. RESULTS: Overall 22.8% reported any
      transportation activity (i.e., to/from work/school), 54.3% reported any moderate
      to vigorous household activity, and 56.6% reported any moderate to vigorous
      leisure activity, all in the past month. Participation in any transportation and
      moderate to vigorous leisure activity was stable over time, while participation
      in any moderate to vigorous household activities and moderate leisure activities
      increased from 1999-2002 to 2003-06. Moderate to vigorous leisure activity was
      significantly higher among those in first trimester compared to third trimester,
      among non-Hispanic white participants compared to women from other race/ethnic
      groups, and among those with health insurance compared to those without. From
      2003 to 2006, 15.3% of pregnant women reported watching 5 h or more of television
      or videos per day. CONCLUSION: These data could be used to monitor trends and set
      national goals for physical activity among pregnant women.

PMID- 20053371
TI  - ACC oxidase genes expressed in the wood-forming tissues of loblolly pine (Pinus
      taeda L.) include a pair of nearly identical paralogs (NIPs).
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) oxidase catalyzes the final reaction of
      the ethylene biosynthetic pathway, converting the unusual cyclic amino acid, ACC,
      into ethylene. Past studies have shown a possible link between ethylene and
      compression wood formation in conifers, but the relationship has received no more
      than modest study at the gene expression level. In this study, a cDNA clone
      encoding a putative ACC oxidase, PtACO1, was isolated from a cDNA library
      produced using mRNA from lignifying xylem of loblolly pine (Pinus taeda) trunk
      wood. The cDNA clone comprised an open reading frame of 1461 bp encoding a
      protein of 333 amino acids. Using PCR amplification techniques, a genomic clone
      corresponding to PtACO1 was isolated and shown to contain three introns with
      typical GT/AG boundaries defining the splice junctions. The PtACO1 gene product
      shared 70% identity with an ACC oxidase from European white birch (Betula
      pendula), and phylogenetic analyses clearly placed the gene product in the ACC
      oxidase cluster of the Arabidopsis thaliana 2-oxoglutarate-dependent dioxygenase
      superfamily tree. The PtACO1 sequence was used to identify additional ACC oxidase
      clones from loblolly pine root cDNA libraries characterized as part of an
      expressed sequence tag (EST) discovery project. The PtACO1 sequence was also used
      to recover additional paralogous sequences from genomic DNA, one of which
      (PtACO2) turned out to be >98% identical to PtACO1 in the nucleotide coding
      sequence, leading to its classification as a "nearly identical paralog" (NIP).
      Quantitative PCR analyses showed that the expression level of PtACO1-like
      transcripts varied in different tissues, as well as in response to hormonal
      treatments and bending. Possible roles for PtACO1 in compression wood formation
      in loblolly pine and the discovery of its NIP are discussed in light of these
      results.

PMID- 20053372
TI  - Symbiont genomics, our new tangled bank.
AB  - Microbial symbionts inhabit the soma and surfaces of most multicellular species
      and instigate both beneficial and harmful infections. Despite their ubiquity, we
      are only beginning to resolve major patterns of symbiont ecology and evolution.
      Here, we summarize the history, current progress, and projected future of the
      study of microbial symbiont evolution throughout the tree of life. We focus on
      the recent surge of data that whole-genome sequencing has introduced into the
      field, in particular the links that are now being made between symbiotic
      lifestyle and molecular evolution. Post-genomic and systems biology approaches
      are also emerging as powerful techniques to investigate host-microbe
      interactions, both at the molecular level of the species interface and at the
      global scale. In parallel, next-generation sequencing technologies are allowing
      new questions to be addressed by providing access to population genomic data, as
      well as the much larger genomes of microbial eukaryotic symbionts and hosts.
      Throughout we describe the questions that these techniques are tackling and we
      conclude by listing a series of unanswered questions in microbial symbiosis that
      can potentially be addressed with the new technologies.

PMID- 20053373
TI  - Functional cholinergic damage develops with amyloid accumulation in young adult
      APPswe/PS1dE9 transgenic mice.
AB  - We investigated the functional characteristics of pre- and postsynaptic
      cholinergic transmission in APPswe/PS1dE9 double transgenic mice at a young age
      (7-10 weeks) before the onset of amyloid plaque formation and at adult age (5-6
      months) at its onset. We compared brain slices from cerebral cortex and
      hippocampus with amyloid deposits to slices from striatum with no amyloid plaques
      by 6 months of age. In young transgenic mice we found no impairments of preformed
      and newly synthesized [(3)H]-ACh release, indicating intact releasing machinery
      and release turnover, respectively. Adult transgenic mice displayed a significant
      increase in preformed [(3)H]-ACh release in cortex but a decrease in hippocampus
      and striatum. The extent of presynaptic muscarinic autoregulation was unchanged.
      Evoked release of newly synthesized [(3)H]-ACh was significantly reduced in the
      cortex and hippocampus but unchanged in the striatum. Carbachol-induced G-protein
      activation in cortical membranes displayed decreased potency but normal efficacy
      in adult animals and no changes in young animals. These results indicate that
      functional pre- and postsynaptic cholinergic deficits are not present in
      APPswe/PS1dE9 transgenic mice before 10 weeks of age, but develop along with beta
      amyloid accumulation in the brain.

PMID- 20053374
TI  - miR-497 regulates neuronal death in mouse brain after transient focal cerebral
      ischemia.
AB  - Dysfunction of the microRNA (miR) network has been emerging as a major regulator
      in neurological diseases. However, little is known about the functional
      significance of unique miRs in ischemic brain damage. Here, we found that miR-497
      is induced in mouse brain after transient middle cerebral artery occlusion (MCAO)
      and mouse N2A neuroblastoma (N2A) cells after oxygen-glucose deprivation (OGD).
      Loss-of-miR-497 function significantly suppresses OGD-induced N2A cell death,
      whereas gain-of-miR-497 function aggravates OGD-induced neuronal loss. Moreover,
      miR-497 directly binds to the predicted 3'-UTR target sites of bcl-2/-w genes.
      Furthermore, knockdown of cerebral miR-497 effectively enhances bcl-2/-w protein
      levels in the ischemic region, attenuates ischemic brain infarction, and improves
      neurological outcomes in mice after focal cerebral ischemia. Taken together, our
      data suggest that miR-497 promotes ischemic neuronal death by negatively
      regulating antiapoptotic proteins, bcl-2 and bcl-w. We raise the possibility that
      this pathway may contribute to the pathogenesis of the ischemic brain injury in
      stroke.

PMID- 20053375
TI  - Expression profiling in peripheral blood reveals signature for penetrance in DYT1
      dystonia.
AB  - DYT1 dystonia is an autosomal-dominantly inherited movement disorder, which is
      usually caused by a GAG deletion in the TOR1A gene. Due to the reduced penetrance
      of approximately 30-40%, the determination of the mutation in a subject is of
      limited use with regard to actual manifestation of symptoms. In the present
      study, we used Affymetrix oligonucleotide microarrays to analyze global gene
      expression in blood samples of 15 manifesting and 15 non-manifesting mutation
      carriers in order to identify a susceptibility profile beyond the GAG deletion
      which is associated with the manifestation of symptoms in DYT1 dystonia. We
      identified a genetic signature which distinguished between asymptomatic mutation
      carriers and symptomatic DYT1 patients with 86.7% sensitivity and 100%
      specificity. This genetic signature could correctly predict the disease state in
      an independent test set with a sensitivity of 87.5% and a specificity of 85.7%.
      Conclusively, this genetic signature might provide a possibility to distinguish
      DYT1 patients from asymptomatic mutation carriers.

PMID- 20053376
TI  - The epigenetics of social adversity in early life: implications for mental health
      outcomes.
AB  - An organism's behavioral and physiological and social milieu influence and are
      influenced by the epigenome, which is composed predominantly of chromatin and the
      covalent modification of DNA by methylation. Epigenetic patterns are sculpted
      during development to shape the diversity of gene expression programs in the
      organism. In contrast to the genetic sequence, which is determined by inheritance
      and is virtually identical in all tissues, the epigenetic pattern varies from
      cell type to cell type and is potentially dynamic throughout life. It is
      postulated here that different environmental exposures, including early parental
      care, could impact epigenetic patterns, with important implications for mental
      health in humans. Because epigenetic programming defines the state of expression
      of genes, epigenetic differences could have the same consequences as genetic
      polymorphisms. Yet in contrast to genetic sequence differences, epigenetic
      alterations are potentially reversible. This review will discuss basic epigenetic
      mechanisms and how epigenetic processes early in life might play a role in
      defining inter-individual trajectories of human behavior. In this regard, we will
      examine evidence for the possibility that epigenetic mechanisms can contribute to
      later-onset neurological dysfunction and disease.

PMID- 20053377
TI  - Galectin-3 contributes to neonatal hypoxic-ischemic brain injury.
AB  - Inflammation induced by hypoxia-ischemia (HI) contributes to the development of
      injury in the newborn brain. In this study, we investigated the role of galectin
      3, a novel inflammatory mediator, in the inflammatory response and development of
      brain injury in a mouse model for neonatal HI. Galectin-3 gene and protein
      expression was increased after injury and galectin-3 was located in activated
      microglia/macrophages. Galectin-3-deficient mice (gal3-/-) were protected from
      injury particularly in hippocampus and striatum. Microglia accumulation was
      increased in the gal3-/- mice but accompanied by decreased levels of total matrix
      metalloproteinase (MMP)-9 and nitrotyrosine. The protection and increase in
      microglial infiltration was more pronounced in male gal3-/- mice. Trophic factors
      and apoptotic markers did not significantly differ between groups. In conclusion,
      galectin-3 contributes to neonatal HI injury particularly in male mice. Our
      results indicate that galectin-3 exerts its effect by modulating the inflammatory
      response.

PMID- 20053378
TI  - B-spline-based stereotactical normalization of brain FDG PET scans in suspected
      neurodegenerative disease: impact on voxel-based statistical single-subject
      analysis.
AB  - A b-spline-based method 'Lobster', originally designed as a general technique for
      non-linear image registration, was tailored for stereotactical normalization of
      brain FDG PET scans. Lobster was compared with the normalization methods of SPM2
      and Neurostat with respect to the impact on the accuracy of voxel-based
      statistical analysis. (i) Computer simulation: Seven representative patterns of
      cortical hypometabolism served as artificial ground truth. They were inserted
      into 26 normal control scans with different simulated severity levels. After
      stereotactical normalization and voxel-based testing, statistical maps were
      compared voxel-by-voxel with the ground truth. This was done at different levels
      of statistical significance. There was a highly significant effect of the
      stereotactical normalization method on the area under the resulting ROC curve.
      Lobster showed the best average performance and was most stable with respect to
      variation of the severity level. (ii) Clinical evaluation: Statistical maps were
      obtained for the normal controls as well as patients with Alzheimer's disease
      (AD, n=44), Lewy-Body disease (LBD, 9), fronto-temporal dementia (FTD, 13), and
      cortico-basal dementia (CBD, 4). These maps were classified as normal, AD, LBD,
      FTD, or CBD by two experienced readers. The stereotactical normalization method
      had no significant effect on classification by of each of the experts, but it
      appeared to affect agreement between the experts. In conclusion, Lobster is
      appropriate for use in single-subject analysis of brain FDG PET scans in
      suspected dementia, both in early diagnosis (mild hypometabolism) and in
      differential diagnosis in advanced disease stages (moderate to severe
      hypometabolism). The computer simulation framework developed in the present study
      appears appropriate for quantitative evaluation of the impact of the different
      processing steps and their interaction on the performance of voxel-based single
      subject analysis.

PMID- 20053379
TI  - Neural response to working memory load varies by dopamine transporter genotype in
      children.
AB  - Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the
      dopamine transporter genotype (DAT1) is associated with Attention Deficit
      Hyperactivity Disorder, a childhood disorder marked by poor executive function.
      We examined whether functional anatomy underlying working memory, a component
      process of executive function, differed by DAT1 in 7-12 year-old typically
      developing children. 10/10 and 9/10 carriers performed a verbal n-back task in
      two functional magnetic resonance imaging (fMRI) runs varying in working memory
      load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy
      was superior in 9/10 than 10/10 carriers in the high but not low load runs.
      Examination of each run separately revealed that frontal-striatal-parietal
      regions were more activated in 9/10 than 10/10 carriers in the high load run; the
      groups did not differ in the low load run. Examination of load effects revealed a
      DAT1xLoad interaction in the right hemisphere in the caudate, our a priori region
      of interest. Exploratory analysis at a more liberal threshold revealed this
      interaction in other basal ganglia regions (putamen, and substantial
      nigra/subthalamic nuclei - SN/STN) and in medial parietal cortex (left
      precuneus). The striatal and parietal regions were more activated in 9/10
      carriers under high than low load, and DAT1 differences (9/10>10/10) were evident
      only under high load. In contrast, SN/STN tended to be more activated in 10/10
      carriers under low than high load and DAT1 differences (10/10>9/10) were evident
      only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with
      reduced performance and a lack of increased basal ganglia involvement under
      higher working memory demands.

PMID- 20053380
TI  - Hippocampal contributions to the processing of architectural ranking.
AB  - Theories of rhetoric and architecture suggest that buildings designed to be high
      ranking according to the Western architectural decorum have more impact on the
      minds of their beholders than low-ranking buildings. Here, we used event-related
      potentials in a visual object categorization task to probe this assumption and to
      examine whether the hippocampus contributes to the processing of architectural
      ranking. We found that early negative potentials between 200 and 400 ms
      differentiated between high- and low-ranking buildings in healthy subjects and
      patients with temporal lobe epilepsy with and without hippocampal sclerosis. By
      contrast, late positive potentials between 400 and 600 ms were higher in
      amplitude to high-ranking buildings only in healthy subjects and TLE patients
      without but not in TLE patients with hippocampal sclerosis. These findings
      suggest that the differentiation between high- and low-ranking buildings entails
      both early visual object selection and late post-model selection processes and
      that the hippocampus proper contributes critically to this second stage of visual
      object categorization.

PMID- 20053381
TI  - In vivo MRI of neural cell migration dynamics in the mouse brain.
AB  - Multipotent neuroblasts (NBs) are produced throughout life by neural stem cells
      in the forebrain subventricular zone (SVZ), and are able to travel long distances
      to the olfactory bulb. On arrival in the bulb, migrating NBs normally replace
      olfactory neurons, raising interest in their potential for novel cell replacement
      therapies in various disease conditions. An understanding of the migratory
      capabilities of NBs is therefore important, but as yet quantitative in vivo
      measurement of cell migration has not been possible. In this study, targeted
      intracerebral injections of iron-oxide particles to the mouse SVZ were used to
      label resident NBs in situ, and their migration was tracked noninvasively over
      time with magnetic resonance imaging (MRI). Quantitative intensity metrics were
      employed to identify labeled cells and to show that cells are able to travel at
      speeds up to 100 microm/h en route to the olfactory bulb, but that distribution
      through the olfactory bulb occurs at a much slower rate. In addition, comparison
      of histological and MRI measures of iron-oxide particle distribution were in
      excellent agreement. Immunohistochemistry analysis 1-3 weeks after labeling
      revealed that the majority of labeled cells in the olfactory bulb were immature
      neurons, although iron-oxide particles were also found in astrocytes and
      microglia. This work indicates that dynamic measurements of endogenous cell
      migration can be made with MRI and represents the first in vivo measurement of NB
      migration rates. The use of MRI in future studies tracking endogenous NB cells
      will permit a more complete evaluation of their role during homeostasis at
      various developmental stages and during disease progression.

PMID- 20053382
TI  - Discovering structure in the space of fMRI selectivity profiles.
AB  - We present a method for discovering patterns of selectivity in fMRI data for
      experiments with multiple stimuli/tasks. We introduce a representation of the
      data as profiles of selectivity using linear regression estimates, and employ
      mixture model density estimation to identify functional systems with distinct
      types of selectivity. The method characterizes these systems by their selectivity
      patterns and spatial maps, both estimated simultaneously via the EM algorithm. We
      demonstrate a corresponding method for group analysis that avoids the need for
      spatial correspondence among subjects. Consistency of the selectivity profiles
      across subjects provides a way to assess the validity of the discovered systems.
      We validate this model in the context of category selectivity in visual cortex,
      demonstrating good agreement with the findings based on prior hypothesis-driven
      methods.

PMID- 20053383
TI  - Confirming white matter fMRI activation in the corpus callosum: co-localization
      with DTI tractography.
AB  - Recently, functional magnetic resonance imaging (fMRI) activation has been
      detected in white matter, despite the widely-held belief that fMRI activation is
      restricted to gray matter. The objective of the current study was to determine
      whether the regions of white matter fMRI activation were structurally connected
      to the functional network in gray matter. To do this, we used fMRI-guided
      tractography to evaluate whether tracts connecting regions of gray matter fMRI
      activation were co-localized with white matter fMRI activation. An established
      interhemispheric transfer task was employed to elicit activation in the corpus
      callosum. Diffusion tensor imaging (DTI) tractography was used to determine the
      existence of tracts that connected regions of gray matter fMRI activation to
      regions of activation in the corpus callosum. Corpus callosum activation was
      detected in the majority of participants. While there was individual variability
      in the location of corpus callosum activation, activation was commonly observed
      in the callosal mid-body, isthmus/splenium, or both. Despite the variability,
      gray matter fMRI-guided tractography identified tracts that were co-localized
      with corpus callosum fMRI activation in all instances. In addition, callosal
      activation had tracts to bilateral gray matter fMRI activation for 7/8
      participants. The results confirmed that the activated regions of the corpus
      callosum were structurally connected to the functional network of gray matter
      regions involved in the task. These findings are an important step towards
      establishing the functional significance of white matter fMRI, and provide the
      foundation for future work combining white matter fMRI and DTI tractography to
      study brain connectivity.

PMID- 20053384
TI  - Characterisation of the BOLD response time course at different levels of the
      auditory pathway in non-human primates.
AB  - Non-human-primate fMRI is becoming increasingly recognised as the missing link
      between the widely applied methods of human imaging and intracortical animal
      electrophysiology. A crucial requirement for the optimal application of this
      method is the precise knowledge of the time course of the Blood Oxygenation Level
      Dependent (BOLD) signal. We mapped the BOLD signal time course in the inferior
      colliculus (IC), medial geniculate body (MGB) and in tonotopically defined fields
      in the auditory cortex of two macaques. The results show little differences in
      the BOLD-signal time courses within the auditory pathway. However, we observed
      systematic differences in the magnitude of the change in the BOLD signal with
      significantly stronger signal changes in field A1 of the auditory cortex compared
      to field R. The measured time course of the signal was in good agreement with
      similar studies in human auditory cortex but showed considerable differences to
      data reported from macaque visual cortex. Consistent with the studies in humans
      we measured a peak in the BOLD response around 4 s after the onset of 2-s
      broadband noise stimuli while previous studies recorded from the primary visual
      cortex of the same species reported the earliest peaks to short visual stimuli
      several seconds later. The comparison of our results with previous studies does
      not support differences in haemodynamic responses within the auditory system
      between human and non-human primates. Furthermore, the data will aid optimal
      design of future auditory fMRI studies in non-human primates.

PMID- 20053385
TI  - Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its
      receptors CCR1+ and CCR5+ in RANKL+ cell migration throughout experimental
      periodontitis in mice.
AB  - Periodontal disease (PD) is characterized by the inflammatory bone resorption in
      response to the bacterial challenge, in a host response that involves a series of
      chemokines supposed to control cell influx into periodontal tissues and determine
      disease outcome. In this study, we investigated the role of chemokines and its
      receptors in the immunoregulation of experimental PD in mice. Aggregatibacter
      actinomycetemcomitans-infected C57Bl/6 (WT) mice developed an intense
      inflammatory reaction and severe alveolar bone resorption, associated with a high
      expression of CCL3 and the migration of CCR5+, CCR1+ and RANKL+ cells to
      periodontal tissues. However, CCL3KO-infected mice developed a similar disease
      phenotype than WT strain, characterized by the similar expression of cytokines
      (TNF-alpha, IFN-gamma and IL-10), osteoclastogenic factors (RANKL and OPG) and
      MMPs (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3), and similar patterns of CCR1+,
      CCR5+ and RANKL+ cell migration. The apparent lack of function for CCL3 is
      possible due the relative redundancy of chemokine system, since chemokines such
      as CCL4 and CCL5, which share the receptors CCR1 and CCR5 with CCL3, present a
      similar kinetics of expression than CCL3. Accordingly, CCL4 and CCL5 kinetics of
      expression after experimental periodontal infection remain unaltered regardless
      the presence/absence of CCL3. Conversely, the individual absence of CCR1 and CCR5
      resulted in a decrease of leukocyte infiltration and alveolar bone loss. When
      CCR1 and CCR5 were simultaneously inhibited by met-RANTES treatment a
      significantly more effective attenuation of periodontitis progression was
      verified, associated with lower values of bone loss and decreased counts of
      leukocytes in periodontal tissues. Our results suggest that the absence of CCL3
      does not affect the development of experimental PD in mice, probably due to the
      presence of homologous chemokines CCL4 and CCL5 that overcome the absence of this
      chemokine. In addition, our data demonstrate that the absence of chemokine
      receptors CCR1+ and CCR5+ attenuate of inflammatory bone resorption. Finally, our
      data shows data the simultaneous blockade of CCR1 and CCR5 with MetRANTEs
      presents a more pronounced effect in the arrest of disease progression,
      demonstrating the cooperative role of such receptors in the inflammatory bone
      resorption process throughout experimental PD.

PMID- 20053386
TI  - Socioeconomic status and bone mineral density in a population-based sample of
      men.
AB  - Overall, socioeconomic status (SES) is inversely associated with poorer health
      outcomes. However, current literature provides conflicting data of the
      relationship between SES and bone mineral density (BMD) in men. In an age
      stratified population-based randomly selected cross-sectional study of men
      (n=1467) we assessed the association between SES and lifestyle exposures in
      relation to BMD. SES was determined by matching the residential address for each
      subject with Australian Bureau of Statistics 2006 census data for the study
      region. BMD was measured at the spine and femoral neck by dual energy X-ray
      absorptiometry. Lifestyle variables were collected by self-report. Regression
      models were age-stratified into younger and older groups and adjusted for age,
      weight, dietary calcium, physical activity, and medications known to affect bone.
      Subjects with spinal abnormalities were excluded from analyses of BMD at the
      spine. In younger men, BMD was highest at the spine in the mid quintiles of SES,
      where differences were observed compared to quintile 1 (1-7%, p<0.05). In older
      men, the pattern of BMD across SES quintiles was reversed, and subjects from mid
      quintiles had the lowest BMD, with differences observed compared to quintile 5 (1
      7%, p<0.05). Differences in BMD at the spine across SES quintiles represent a
      potential 1.5-fold increase in fracture risk for those with the lowest BMD. There
      were no differences in BMD at the femoral neck. Further research is warranted
      which examines the mechanisms that may underpin differences in BMD across SES
      quintiles and to address the current paucity of data in this field of enquiry.

PMID- 20053387
TI  - RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2
      cells.
AB  - The runt-related transcriptional factor RUNX2 is an essential mediator of the
      osteoblast phenotype and plays a pivotal role in the process of osteoblast
      differentiation. The involvement of RUNX2 includes the regulation of genes that
      are important in committing cells to the osteoblast lineage. Increasing evidences
      are consistent with a requirement of RUNX2 for stringent control of osteoblast
      proliferation and recent data even suggested that RUNX2 might act as a
      proapoptotic factor. Among the cytokines described as modulators of osteoblast
      functions, TNFalpha affects both apoptosis and the differentiation rate from
      mesenchymal precursor cells of osteoblast. Thus we evaluated on the human
      osteosarcoma cell line SaOs-2 stably transfected with a RUNX2 dominant negative
      construct (DeltaRUNX2) the effects of serum and TNFalpha on proliferation and
      apoptosis. In this study we showed that SaOs-2 clones expressing high levels of
      DeltaRUNX2 presented a higher proliferation rate than clones transfected with an
      empty vector. This increase in cell growth was accompanied by a rise in cyclins
      A1, B1 and E1 expression and a decrease in the cyclin inhibitor p21. Moreover we
      observed that the expression of the RUNX2 transgene protected the SaOs-2 cells
      from the antiproliferative and the apoptotic effects induced by TNFalpha. This
      was accompanied by the inhibition of Bax and activation of Bcl2 expression.
      Experiments done on SaOs-2 cells transiently transfected with siRNA confirmed
      that RUNX2 represents a critical link between cell fate, proliferation and growth
      control. This study also suggested that RUNX2 might control osteoblastic growth
      depending on the differentiation stage of the cells by regulating expression of
      elements involved in hormones and cytokines sensitivity.

PMID- 20053389
TI  - Features of graded category structure: Generalizing the family resemblance and
      polymorphous concept models.
AB  - Many real-world categories contain graded structure: certain category members are
      rated as more typical or representative of the category than others. Research has
      shown that this graded structure can be well predicted by the degree of
      commonality across the feature sets of category members. We demonstrate that two
      prominent feature-based models of graded structure, the family resemblance (Rosch
      & Mervis, 1975) and polymorphous concept models (Hampton, 1979), can be
      generalized via the contrast model (Tversky, 1977) to include both common and
      distinctive feature information, and apply the models to the prediction of
      typicality in 11 semantic categories. The results indicate that both types of
      feature information play a role in the prediction of typicality, with common
      features weighted more heavily for within-category predictions, and distinctive
      features weighted more heavily for contrast-category predictions. The same
      pattern of results was found in additional analyses employing rated goodness and
      exemplar generation frequency. It is suggested that these findings provide
      insight into the processes underlying category formation and representation.

PMID- 20053388
TI  - Inhibition of PHOSPHO1 activity results in impaired skeletal mineralization
      during limb development of the chick.
AB  - PHOSPHO1 is a bone-specific phosphatase implicated in the initiation of inorganic
      phosphate generation for matrix mineralization. The control of mineralization is
      attributed to the actions of tissue-nonspecific alkaline phosphatase (TNAP).
      However, matrix vesicles (MVs) containing apatite crystals are present in
      patients with hypophosphatasia as well as TNAP null (Akp2(-/-)) mice. It is
      therefore likely that other phosphatases work with TNAP to regulate matrix
      mineralization. Although PHOSPHO1 and TNAP expression is associated with MVs, it
      is not known if PHOSPHO1 and TNAP are coexpressed during the early stages of limb
      development. Furthermore, the functional in vivo role of PHOSPHO1 in matrix
      mineralization has yet to be established. Here, we studied the temporal
      expression and functional role of PHOSPHO1 within chick limb bud mesenchymal
      micromass cultures and also in wild-type and talpid(3) chick mutants. These
      mutants are characterized by defective hedgehog signalling and the absence of
      endochondral mineralization. The ability of in vitro micromass cultures to
      differentiate and mineralize their matrix was temporally associated with
      increased expression of PHOSPHO1 and TNAP. Comparable changes in expression were
      noted in developing embryonic legs (developmental stages 23-36HH). Micromass
      cultures treated with lansoprazole, a small-molecule inhibitor of PHOSPHO1
      activity, or FGF2, an inhibitor of chondrocyte differentiation, resulted in
      reduced alizarin red staining (P<0.05). FGF2 treatment also caused a reduction in
      PHOSPHO1 (P<0.001) and TNAP (P<0.001) expression. Expression analysis by whole
      mount RNA in situ hybridization correlated with qPCR micromass data and
      demonstrated the existence of a tightly regulated pattern of Phospho1 and Tnap
      expression which precedes mineralization. Treatment of developing embryos for 5
      days with lansoprazole completely inhibited mineralization of all leg and wing
      long bones as assessed by alcian blue/alizarin red staining. Furthermore, long
      bones of the talpid(3) chick mutant did not express Phospho1 or Tnap whereas flat
      bones mineralized normally and expressed both phosphatases. In conclusion, this
      study has disclosed that PHOSPHO1 expression mirrors that of TNAP during
      embryonic bone development and that PHOSPHO1 contributes to bone mineralization
      in developing chick long bones.

PMID- 20053390
TI  - Does monocular visual space contain planes?
AB  - The issue of the existence of planes-understood as the carriers of a nexus of
      straight lines-in the monocular visual space of a stationary human observer has
      never been addressed. The most recent empirical data apply to binocular visual
      space and date from the 1960s (Foley, 1964). This appears to be both the first
      and the last time this basic issue was addressed empirically. Yet the question is
      of considerable conceptual interest. Here we report on a direct empirical test of
      the existence of planes in monocular visual space for a group of sixteen
      experienced observers. For the majority of these observers monocular visual space
      lacks a projective structure, albeit in qualitatively different ways. This
      greatly reduces the set of viable geometrical models. For example, it rules out
      all the classical homogeneous spaces (the Cayley-Klein geometries) such as the
      familiar Luneburg model. The qualitatively different behavior of experienced
      observers implies that the generic population might well be inhomogeneous with
      respect to the structure of visual space.

PMID- 20053391
TI  - Acute endophthalmitis after cataract surgery: 250 consecutive cases treated at a
      tertiary referral center in the Netherlands.
AB  - PURPOSE: To evaluate the clinical characteristics, bacterial culture, and visual
      outcome of patients with acute endophthalmitis after cataract surgery. DESIGN:
      Retrospective consecutive interventional case series. METHODS: Clinical notes
      from patients treated for acute endophthalmitis after cataract surgery in a
      single center from 1996 to 2006 were reviewed. Patients with less than 1 month of
      follow-up and missing bacterial cultures were excluded. Vitreous biopsy or
      primary vitrectomy followed by intravitreal injection of vancomycin and
      ceftazidime (+/- prednisolone) was performed. Main outcome measures were
      bacterial culture and final visual acuity. RESULTS: Bacterial cultures (total 250
      cases) showed bacterial growth in 166 cases (66.4%). From these 166 cultures, 89
      (53.6%) revealed gram-positive coagulase-negative, 63 (38.0%) other gram
      positive, 10 (6.0%) gram-negative, and 4 (2.4%) polymicrobial cultures. Vitreous
      biopsy with intravitreal antibiotics injection was performed in 225 (90.0%) of
      cases. Primary vitrectomy with intravitreal antibiotics was performed in 25 eyes
      (10.0%). Final visual acuity >/=0.5 was achieved in 129 (51.6%) of all cases, 54
      (60.7%) of the 89 gram-positive coagulase-negative cultures, 20 (31.7%) of the 63
      other gram-positive cultures, 5 (50.0%) of the 10 gram-negative cultures, and 9
      (45.0%) of the 20 Staphylococcus aureus cultures. There was no additional effect
      for treatment by primary vitrectomy or intravitreal prednisolone. CONCLUSIONS:
      Treatment outcome after endophthalmitis is highly dependent on the causative
      organism. Treatment outcomes for gram-negative bacteria and S. aureus may be
      better than previously reported. Prompt treatment of endophthalmitis remains
      essential and the role of complete primary vitrectomy remains subject to debate.

PMID- 20053392
TI  - Comparison of intravitreal triamcinolone acetonide with photodynamic therapy and
      intravitreal bevacizumab with photodynamic therapy for retinal angiomatous
      proliferation.
AB  - PURPOSE: To compare the efficacy of combined therapy with intravitreal
      triamcinolone (IVTA) and photodynamic therapy (PDT; IVTA plus PDT) with
      intravitreal bevacizumab (IVB) and PDT (IVB plus PDT) for patients with retinal
      angiomatous proliferation (RAP). DESIGN: Retrospective, observational case
      series. METHODS: We retrospectively reviewed 25 treatment-naive eyes of 22
      Japanese patients (11 men, 11 women) with retinal angiomatous proliferation.
      Twelve eyes of 11 patients were treated with combined therapy of IVTA plus PDT
      from September 1, 2004, through July 31, 2006. Thirteen eyes of 11 patients were
      treated with combined therapy of IVB plus PDT from February 1, 2007, through
      January 31, 2008. RESULTS: In 12 eyes treated with IVTA plus PDT, the mean best
      corrected visual acuity (BCVA) levels at baseline and 12 months were 0.29 and
      0.13, respectively. A significant (P < .05) decline in the mean BCVA from
      baseline was observed at 12 months. In 13 eyes treated with IVB plus PDT, the
      mean BCVA levels at baseline and 12 months were 0.25 and 0.37. A significant (P <
      .05) improvement in the mean BCVA from baseline was observed. At 12 months, the
      difference in BCVA between the 2 groups was significant (P < .05). The mean
      numbers of treatments at 12 months in the IVTA plus PDT group and the IVB plus
      PDT group were 2.7 and 1.6, respectively. The difference between the 2 treatments
      reached significance (P < .05). No complications developed. CONCLUSIONS: Compared
      with IVTA plus PDT, IVB plus PDT was significantly more effective in maintaining
      and improving visual acuity and in reducing the number of treatment for patients
      with retinal angiomatous proliferation.

PMID- 20053393
TI  - Prevention of marital instability and distress. Results of an 11-year
      longitudinal follow-up study.
AB  - Divorce and destructive couple conflict are major risk factors for many forms of
      dysfunction and psychopathology in the family. Couple relationship education has
      been offered in an attempt to reduce those risks and enhance couple outcomes. The
      current effectiveness study had two aims: to assess (a) the long-term effects of
      relationship education and (b) the ability of partners to remember the skills
      typically taught during the communication skills training. One hundred and one
      couples from two studies, in which the effectiveness of the EPL (Ein
      Partnerschaftliches Lernprogramm fur Paare [A Learning Program for Married
      Couples]) was investigated, were followed-up 11 years after the training. In the
      first study, EPL-takers had a significantly lower divorce and separation rate
      (27.5%) than non-EPL-takers (52.6%). This finding was replicated in a second
      study, showing a 20% dissolution rate in EPL-takers. For those couples still
      together, the rate of happy relationships was 80% at the eleven-year follow-up -
      thus, there is optimism for longer married couples who are willing to focus on
      improving their relationships. Only about 55% of the partners could remember at
      least one speaker skill whereas 70% remembered at least one listening skill
      taught during EPL. Consequences for prevention programs in the couple domain are
      discussed.

PMID- 20053394
TI  - Modelling of beta-D-glucopyranose ring distortion in different force fields: a
      metadynamics study.
AB  - Modelling of carbohydrate conformations is a challenging task for force field
      developers. Three carbohydrate force fields, namely GLYCAM06, GROMOS 45a4 and
      OPLS were evaluated. Free energies of different ring conformations of beta-D
      glucopyranose were calculated using metadynamics in vacuum as well as in
      explicitly modelled water. All three force fields model the (4)C(1) conformation
      as the most stable by at least 6kJ/mol, as compared to other conformations.
      Interconversion from the (4)C(1) to any other conformation is associated with a
      barrier of no lower than 26kJ/mol. The free energy surface calculated in the
      GLYCAM06 force field is in remarkably good agreement with the recent Car
      Parrinello metadynamics study. The effect of a water environment is relatively
      low and analogous in all tested force fields. Namely, the presence of water
      stabilizes the upper-left ((3,O)B) versus bottom-right (B(3,O)) area of
      Stoddard's plot, relative to the situation in vacuum. Comparison of free and
      potential surfaces is also provided for vacuum calculations.

PMID- 20053395
TI  - Comparison of the anti-allergic activity of Syk inhibitors with optimized Syk
      siRNAs in FcepsilonRI-activated RBL-2H3 basophilic cells.
AB  - Spleen tyrosine kinase (Syk) binds ITAM-bearing receptors in a wide variety of
      cell types. One such example is the activation of mast cells, basophils and
      eosinophils via the stimulation of the FcepsilonRI receptor by IgE/allergen
      complexes. The possible role of Syk in inflammatory signaling cascades has led to
      the development of pharmacological agents designed to block the Syk catalytic
      domain as potential novel therapeutics. Whilst the enzymatic activity of Syk
      lends towards the design of small-molecule inhibitors, other attention has
      focused on the possibility of targeting Syk expression using anti-sense
      oligonucleotides as an alternate means of anti-inflammatory therapy. In this
      study, we compared the ability of multiple optimized Syk siRNA sequences and
      small-molecule Syk inhibitors to block FcepsilonRI-mediated signal transduction,
      degranulation and TNFalpha secretion in the basophilic cell line RBL-2H3. We also
      characterized the specificity of each siRNA sequence with regards to off-target
      induction of the interferon-inducible gene IFIT1. We identified a single siRNA
      sequence, which displayed a favorable profile of efficient Syk knockdown,
      blockage of FcepsilonRI-mediated signal transduction, degranulation and TNFalpha
      secretion and a lack of IFIT1 induction. The effect of this siRNA was comparable
      to that of the Syk kinase domain inhibitors BAY61-3606 and R406. The
      identification of an active and specific Syk siRNA could be a basis for the
      development of therapeutic Syk siRNAs against inflammatory diseases.

PMID- 20053396
TI  - Fast segmentation of bone in CT images using 3D adaptive thresholding.
AB  - Fast bone segmentation is often important in computer-aided medical systems.
      Thresholding-based techniques have been widely used to identify the object of
      interest (bone) against dark backgrounds. However, the darker areas that are
      often present in bone tissue may adversely affect the results obtained using
      existing thresholding-based segmentation methods. We propose an automatic, fast,
      robust and accurate method for the segmentation of bone using 3D adaptive
      thresholding. An initial segmentation is first performed to partition the image
      into bone and non-bone classes, followed by an iterative process of 3D
      correlation to update voxel classification. This iterative process significantly
      improves the thresholding performance. A post-processing step of 3D region
      growing is used to extract the required bone region. The proposed algorithm can
      achieve sub-voxel accuracy very rapidly. In our experiments, the segmentation of
      a CT image set required on average less than 10s per slice. This execution time
      can be further reduced by optimizing the iterative convergence process.

PMID- 20053397
TI  - Internal fixation of intracapsular hip fractures with a dynamic locking plate:
      initial experience and results for 83 patients treated with a new implant [Injury
      2009. doi:10.1016/j.injury.2009.09.004].

PMID- 20053398
TI  - Sublingual misoprostol for first trimester termination of pregnancy.
AB  - OBJECTIVES: To compare blood loss, efficiency, and acceptability of repeated
      doses of sublingual misoprostol with the standard Tunisian regimen of
      mifepristone-misoprostol for first trimester medical abortion. METHODS: A
      prospective randomized trial of 252 healthy pregnant women requesting medical
      abortion in the first trimester (up to 56 days). Participants were randomized to
      receive 200mg of oral mifepristone followed by 400 microg of oral misoprostol
      (group 1) or 800 microg of sublingual misoprostol repeated every 4 hours for up
      to a maximum of 3 doses (group 2). Primary outcome was blood loss assessed by
      decrease in hematocrit. RESULTS: Mean decrease in hematocrit at follow-up was
      significantly greater in group 1 than in group 2 (3.65%+/-1.18% vs 2.69%+/-1.89%,
      respectively; P=0.02). There was no difference in efficiency rates between groups
      1 and 2 (94.5% vs 92.1%; P=0.7). Comparable proportions of women experiencing at
      least one adverse effect after misoprostol administration were reported in groups
      1 and 2 (81.7% vs 79.4%; P=0.75). CONCLUSION: Compared with the most widely used
      regimen in Tunisia (mifepristone-misoprostol), sublingual misoprostol alone
      induces less blood loss (although not clinically significant); it is less
      expensive and offers reduced interval time to expulsion.

PMID- 20053399
TI  - Prevention of postpartum hemorrhage at home birth in Afghanistan.
AB  - OBJECTIVE: To test the safety, acceptability, feasibility, and effectiveness of
      community-based education and distribution of misoprostol for prevention of
      postpartum hemorrhage at home birth in Afghanistan. METHODS: A nonrandomized
      experimental control design in rural Afghanistan. RESULTS: A total of 3187 women
      participated: 2039 in the intervention group and 1148 in the control group. Of
      the 1421 women in the intervention group who took misoprostol, 100% correctly
      took it after birth, including 20 women with twin pregnancies. Adverse effect
      rates were unexpectedly lower in the intervention group than in the comparison
      group. Among women in the intervention group, 92% said they would use misoprostol
      in their next pregnancy. In the intervention area where community-based
      distribution of misoprostol was introduced, near-universal uterotonic coverage
      (92%) was achieved compared with 25% coverage in the control areas. CONCLUSION:
      In Afghanistan, community-based education and distribution of misoprostol is
      safe, acceptable, feasible, and effective. This strategy should be considered for
      other countries where access to skilled attendance is limited.

PMID- 20053400
TI  - Uterotonic use at home births in low-income countries: a literature review.
AB  - OBJECTIVES: This literature review compiles data on rates of use, indications,
      types of provider, mode of administration, and dose of uterotonics used for home
      births in low-income countries, and identifies gaps meriting further research.
      METHODS: Published and unpublished English language articles from 1995 through
      2008 pertaining to home use of uterotonics were identified via electronic
      searches of medical and social science databases. In addition, bibliographies of
      articles were examined for eligible studies. Data were abstracted and analyzed by
      the objectives outlined for this review. RESULTS: Twenty-three articles met the
      inclusion/exclusion criteria. Use rates of uterotonics at home births ranged
      widely from 1% to 69%, with the large majority of observations from South Asia.
      Descriptive studies suggest that home use of uterotonics before delivery of the
      baby are predominantly administered by nonprofessionals to accelerate labor, and
      are not perceived as unsafe. CONCLUSIONS: To achieve maximum benefit and minimal
      harm, programs that increase access to uterotonics for postpartum hemorrhage
      prevention must take into account existing practices among pregnant women.
      Further research regarding access to uterotonics and intervention studies for
      provider behavior change regarding uterotonic use is warranted.

PMID- 20053401
TI  - Home use of misoprostol to prevent PPH. Editor's Comment.

PMID- 20053402
TI  - Social support interventions and mood status post stroke: a review.
AB  - OBJECTIVE: Psychological consequences of stroke are important determinants of
      health-related quality of life. As many as one-third of individuals with stroke
      will experience post-stroke depression; however, perceived social support may be
      protective in terms of both onset and duration of depressed mood. Improvement of
      available social support could be an important strategy in reducing or preventing
      psychiatric distress and warding off post-stroke depression. The present paper
      will examine the impact of social support interventions on depression or mood
      status in individuals with stroke. DESIGN: Literature review. DATA SOURCES:
      PubMed, CINAHL, EMBASE, PsychINFO and Cochrane Collection databases. REVIEW
      METHODS: Descriptions of study participants and interventions, method and timing
      of the assessment for depression or mood and results pertaining to those outcomes
      were abstracted from identified studies. Each study was assessed in terms of
      methodological quality. Results of similar treatments were compared and evaluated
      descriptively. RESULTS: Ten (10) randomized controlled trials were identified for
      inclusion in the present review. Seven examined similar home-based support and
      care coordination interventions including family support organizers and nursing
      outreach programs. The three remaining studies described: (i) a social support
      intervention, (ii) family counselling in addition to education and (iii) a
      social/occupational day service. Only one trial describing a care coordination
      model reported a significant, positive effect on depression over time associated
      with receipt of the trial intervention. CONCLUSIONS: Identified components of
      care, which distinguished the sole successful trial from those that were
      unsuccessful, include early initiation, increased intensity of regularly
      scheduled, worker-initiated contact, ongoing assessment including screening for
      depression and provision of counselling as required. Future studies should
      incorporate these elements as well as address methodological issues.

PMID- 20053403
TI  - Optimal anthropometric factor cutoffs for hyperglycemia, hypertension and
      dyslipidemia for the Taiwanese population.
AB  - BACKGROUND: Optimal cutoffs for obesity indices are rarely studied in Asians. We
      evaluated these cutoffs for diabetes, hypertension, dyslipidemia and any risk
      factor for the Taiwanese general population. METHODS: Body mass index (BMI),
      waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHeiR) and
      other data for 4683 (2280 men and 2403 women) participants of the population
      based Taiwanese Survey on Hypertension, Hyperglycemia and Hyperlipidemia were
      used. Areas under curves (AUCs) were analyzed and optimal cutoffs were estimated
      by maximizing the sums of sensitivity and specificity. Potential confounders
      included age, smoking, alcohol, betel nut chewing and exercise. RESULTS: Optimal
      cutoffs for men and women, respectively, were 23.7-26.3 and 22.1-23.2 kg/m2 for
      BMI; 85.0-87.0 and 74.0-83.0 cm for WC; 0.87-0.90 and 0.78-0.83 for WHR; and 0.48
      0.52 and 0.48-0.52 for WHeiR. AUCs were not significantly different among the
      indices for diabetes in men and for hypertension in women. In men, WHR was
      significantly inferior to the other indices for predicting hypertension,
      dyslipidemia and any risk factor. In women, BMI was significantly inferior to the
      others for diabetes. For dyslipidemia and any risk factor in women, WHeiR showed
      the largest AUCs and significant differences were seen in the following pairs:
      WHeiR vs. BMI and WHeiR vs. WHR for dyslipidemia and WC vs. WHR and WHeiR vs. WHR
      for any risk factor. CONCLUSIONS: WC and WHeiR have similar efficacy and are
      superior to BMI and WHR. However, WHeiR has the extra benefit of a unisex cutoff
      within a narrow range.

PMID- 20053404
TI  - Do genome-wide association scans provide additional information on the variation
      of plasma adiponectin concentrations?

PMID- 20053405
TI  - Sex and age interaction with genetic association of atherogenic uric acid
      concentrations.
AB  - BACKGROUND: High serum uric acid levels are associated with gout, atherosclerosis
      and cardiovascular disease. Three genes (SLC2A9, ABCG2, and SLC17A3) were
      reported to be involved in the regulation of uric acid levels. RESEARCH:  DESIGN
      AND METHODS: SNPs rs2231142 (ABCG2) and rs1165205 (SLC17A3) were genotyped in
      three cohorts (n=4492) and combined with previously genotyped SNPs within SLC2A9
      (rs6855911, rs7442295, rs6449213, rs12510549). RESULTS: Each copy of the minor
      allele decreased uric acid levels by 0.30-0.38 mg/dL for SLC2A9 (p values: 10(
      20)-10(-36)) and increased levels by 0.34 mg/dL for ABCG2 (p=1.1x10(-16)).
      SLC17A3 influenced uric acid levels only modestly. Together the SNPs showed
      graded associations with uric acid levels of 0.111 mg/dL per risk allele
      (p=3.8x10(-42)). In addition, we observed a sex-specific interaction of age with
      the association of SLC2A9 SNPs with uric acid levels, where increasing age
      strengthened the association of SNPs in women and decreased the association in
      men. CONCLUSIONS: Genetic variants within SLC2A9,ABCG2 and SLC17A3 show highly
      significant associations with uric acid levels, and for SNPs within SLC2A9 this
      association is strongly modified by age and sex.

PMID- 20053406
TI  - Characterization of adsorption processes in analytical liquid-solid
      chromatography.
AB  - This review discusses nonlinear chromatographic methods of importance for proper
      characterization of the adsorption processes in analytical chromatographic
      systems, with focus on reversed-phase liquid chromatography. Linear methods such
      as the linear solvation energy relationship (LSER) method and the Snyder-Dolan
      hydrophobic-subtraction model will also be reviewed briefly. The nonlinear
      methods for adsorption isotherm determination and the tools for further treatment
      of the nonlinear adsorption data will be extensively treated in a way suitable
      for the general chromatographer. Applications of the various methods will be
      given and the outcome and conclusions will be discussed. Special emphasis will be
      placed on discussing the possibilities of combining linear and nonlinear methods
      in order to obtain a deeper and more complete investigation of the interactions
      in the actual phase system.

PMID- 20053407
TI  - Supercritical fluid chromatography hyphenated with twin comprehensive two
      dimensional gas chromatography for ultimate analysis of middle distillates.
AB  - This paper reports the conditions of online hyphenation of supercritical fluid
      chromatography (SFC) with twin comprehensive two-dimensional gas chromatography
      (twin-GCxGC) for detailed characterization of middle distillates; this is
      essential for a better understanding of reactions involved in refining processes.
      In this configuration, saturated and unsaturated compounds that have been
      fractionated by SFC are transferred on two different GC x GC columns sets (twin
      GCxGC) placed in the same GC oven. Cryogenic focusing is used for transfer of
      fractions into the first dimension columns before simultaneous GCxGC analysis of
      both saturated and unsaturated fractions. The benefits of SFC-twin-GC x GC are
      demonstrated for the extended alkane, iso-alkane, alkene, naphthenes and
      aromatics analysis (so-called PIONA analysis) of diesel samples which can be
      achieved in one single injection. For that purpose, saturated and unsaturated
      compounds have been separated by SFC using a silver loaded silica column prior to
      GC x GC analysis. Alkenes and naphthenes are quantitatively recovered in the
      unsaturated and saturated fractions, respectively, allowing their identification
      in various diesel samples. Thus, resolution between each class of compounds is
      significantly improved compared to a single GCxGC run, and for the first time, an
      extended PIONA analysis of diesel samples is presented.

PMID- 20053408
TI  - Editorial on "Characterization of adsorption processes in analytical liquid-solid
      chromatography" by T. Fornstedt.

PMID- 20053409
TI  - Animal models of myocardial and vascular injury.
AB  - Over the past century, numerous animal models have been developed in an attempt
      to understand myocardial and vascular injury. However, the successful translation
      of results observed in animals to human therapy remains low. To understand this
      problem, we present several animal models of cardiac and vascular injury that are
      of particular relevance to the cardiac or vascular surgeon. We also explore the
      potential clinical implications and limitations of each model with respect to the
      human disease state. Our results underscore the concept that animal research
      requires an in-depth understanding of the model, animal physiology, and the
      potential confounding factors. Future outcome analyses with standardized animal
      models may improve translation of animal research from the bench to the bedside.

PMID- 20053410
TI  - Incidence of rotational vertigo in supratentorial stroke: a prospective analysis
      of 112 consecutive patients.
AB  - BACKGROUND: Single cases with hemispheric, cortical or subcortical, ischemic
      lesions presenting with rotational vertigo (RV), that challenge the notion of
      infratentorial or peripheral generation of RV have been published, but the
      incidence of this symptom in a larger series is unknown. The aim of this study
      was to investigate whether acute hemispheric cerebrovascular lesions cause
      vertiginous sensations with particular emphasis on RV. METHODS: A total of 112
      consecutive stroke patients were assessed in a prospective single-center study
      over a 22-month inclusion period. Rotational or other vertiginous sensations were
      assessed using a structured 5-item questionnaire and patients with vertigo were
      further evaluated with Yardley's Vertigo Symptom Scale. All subjects underwent
      standard clinical neuro-ophthalmological and neuro-otological testing and data
      were correlated to imaging findings. RESULTS: RV was absent among our patients.
      Few subjects reported non-rotational vertiginous sensations with stroke onset.
      These were mainly right-hemispheric strokes with concomitant subcortical
      leukoaraiosis. CONCLUSION: In this case series we did not find any patients with
      spinning sensations which is supportive of the dogma that supratenotrial lesions
      do not cause RV. Certain hemispheric stroke patterns, however, may be related to
      non-rotational dizziness.

PMID- 20053411
TI  - [Prognostic markers in heart failure. Current status].

PMID- 20053412
TI  - [Homage to Jules Hardy, pioneer of modern pituitary surgery].

PMID- 20053414
TI  - Assessing the efficiency of a pharmacokinetic-based algorithm for target
      controlled infusion of ketamine in ponies.
AB  - The objective of this study was to assess a pharmacokinetic algorithm to predict
      ketamine plasma concentration and drive a target-controlled infusion (TCI) in
      ponies. Firstly, the algorithm was used to simulate the course of ketamine
      enantiomers plasma concentrations after the administration of an intravenous
      bolus in six ponies based on individual pharmacokinetic parameters obtained from
      a previous experiment. Using the same pharmacokinetic parameters, a TCI of S
      ketamine was then performed over 120 min to maintain a concentration of 1
      microg/mL in plasma. The actual plasma concentrations of S-ketamine were measured
      from arterial samples using capillary electrophoresis. The performance of the
      simulation for the administration of a single bolus was very good. During the
      TCI, the S-ketamine plasma concentrations were maintained within the limit of
      acceptance (wobble and divergence <20%) at a median of 79% (IQR, 71-90) of the
      peak concentration reached after the initial bolus. However, in three ponies the
      steady concentrations were significantly higher than targeted. It is hypothesized
      that an inaccurate estimation of the volume of the central compartment is partly
      responsible for that difference. The algorithm allowed good predictions for the
      single bolus administration and an appropriate maintenance of constant plasma
      concentrations.

PMID- 20053413
TI  - [Evacuation of chronic subdural hematomas with the Twist-Drill technique: Results
      of a randomized prospective study comparing 48-h and 96-h drainage duration].
AB  - BACKGROUND AND PURPOSE: Technical modalities for the evacuation of chronic
      subdural hematomas are still controversial. The Twist-Drill technique with closed
      system drainage is becoming more widely used, but the influence of drainage
      duration on outcome has not been studied yet and therefore is still being
      debated. METHODS: A prospective randomized study was conducted, comparing the
      results between two drainage durations. Forty-eight hours (Group I; n=35
      patients) and 96 h (Group II; n=30 patients). RESULTS: The two groups had almost
      identical characteristics due to randomization. The mean volume of liquid drained
      was 120 ml in the first group and 285 ml in the second, a statistically
      significant difference. The rate of incomplete evacuation versus the rate of
      recurrence did not show any significant difference between Group I (5.7 % and
      11.4 %, respectively) and Group II (3.3 % and 10 %, respectively). The rate of
      postoperative complications was 10.7 % in Group I but 26.9 % in Group II, with a
      respective 3.8 % and 11.4 % mortality rate, proving a statistically significant
      difference. Clinical improvement observed at discharge was 85.7 % and 84.6 % in
      Group I and Group II, respectively. CONCLUSION: With comparable recurrence and
      improvement rates, our study demonstrates that it is much more advantageous to
      remove the catheter at 48 h than leave it in for a longer duration. Not only is
      bed rest reduced, but the rate of morbidities is also significantly decreased.

PMID- 20053415
TI  - Corrosion in a distribution system: Steady water and its composition.
AB  - Corrosion processes in drinking water distribution systems have been investigated
      for years. This paper proves the existence of a layer of steady water surrounding
      and partly filling corrosion scale in corroded water pipes. It is expected that
      steady water may substantially influence the corrosion. The idea of steady water
      explains why longer retention times would lead to more turbid waters containing
      more suspended Fe oxides (hydroxides). During stagnation period stagnant water
      mixes partially with steady water and the compensation of ions' concentration as
      well as particle diffusion is observed. Steady water is rich in ions and has
      reductive properties causing quick disappearance of nitrates and unwanted ammonia
      formation. Ammonia in turn may be responsible for fast oxygen and chlorine decay
      in the distribution system due to nitrification. Nitrates may also undergo
      denitrification in steady water, i.e. they would support bacterial existence in
      the distribution system. Such an environment makes favourable conditions for
      sulphate reducing bacteria and in fact in all of the steady water samples we have
      detected sulphides. Moreover, our results have shown that considerable amounts of
      assimilable organic carbon (AOC) can be formed in the corroded distribution
      system.

PMID- 20053416
TI  - Occurrence of arsenic in core sediments and groundwater in the Chapai-Nawabganj
      District, northwestern Bangladesh.
AB  - Groundwater and core sediments of two boreholes (to a depth of 50m) from the
      Chapai-Nawabganj area in northwestern Bangladesh were collected for arsenic
      concentration and geochemical analysis. Groundwater arsenic concentrations in the
      uppermost aquifer (10-40m of depth) range from 2.8microgL(-1) to 462.3microgL(
      1). Groundwater geochemical conditions change from oxidized to successively more
      reduced, higher As concentration with depth. Higher sediment arsenic levels
      (55mgkg(-1)) were found within the upper 40m of the drilled core samples. X-ray
      absorption near-edge structure spectroscopy was employed to elucidate the arsenic
      speciation of sediments collected from two boreholes. Environmental scanning
      electron microscopy and transmission X-ray microscopy were used to investigate
      the characteristics of FeOOH in sediments which adsorb arsenic. In addition, a pH
      Eh diagram was drawn using the Geochemist's Workbench (GWB) software to elucidate
      the arsenic speciation in groundwater. The dominant groundwater type is Ca-HCO(3)
      with high concentrations of As, Fe and Mn but low levels of NO(3)(-) and SO(4)(2
      ). Sequential extraction analysis reveals that Mn and Fe hydroxides and organic
      matter are the major leachable solids carrying As. High levels of arsenic
      concentration in aquifers are associated with fine-grained sediments. Fluorescent
      intensities of humic substances indicate that both groundwater and sediments in
      this arsenic hotspot area contain less organic matter compared to other parts of
      Bengal basin. Statistical analysis clearly shows that As is closely associated
      with Fe and Mn in sediments while As is better correlated with Mn in groundwater.
      These correlations along with results of sequential leaching experiments suggest
      that reductive dissolution of MnOOH and FeOOH mediated by anaerobic bacteria
      represents an important mechanism for releasing arsenic into the groundwater.

PMID- 20053417
TI  - Transport and interaction of arsenic, chromium, and copper associated with CCA
      treated wood in columns of sand and sand amended with peat.
AB  - Laboratory column leaching experiments were conducted to investigate the
      transport and interaction of As, Cr, and Cu associated with CCA-treated wood in
      sand with and without peat amendment. Results showed that leaching behavior of
      As, Cr, and Cu in these substrates were totally different. Substrate
      characteristics and microorganism activity posed distinct effects on the
      transport and transformation of these three elements. Arsenic was rapidly leached
      out from the columns with or without the amendment of peat, while Cr remained in
      all columns during the entire experimental period (215d). Copper was leached out
      only in the substrate column without peat. The presence of microorganism clearly
      facilitated the transport of As, while it did not show obvious effects on the
      transport of Cr and Cu. Interactions among these three elements were observed
      during the processes of adsorption and transport. The adsorption of Cu on soil
      was enhanced with the adsorption of As, likely caused by a more negatively
      charged soil surface because of As adsorption. The adsorption of Cr on soil
      increased the adsorption of As due to the additional As binding sites induced by
      Cr adsorption. These results suggest that As concentrations in the soil affected
      by CCA-treated wood could largely exceed predictions based on soil adsorption
      capacity for As. The evaluation of the impact on human health associated with CCA
      treated wood should take consideration of the distinct transport characteristics
      of three elements and their interactions in soils.

PMID- 20053418
TI  - Dual body burdens of polychlorinated biphenyls and polybrominated diphenyl ethers
      among local residents in an e-waste recycling region in Southeast China.
AB  - E-waste recycling resulted in serious pollution of polychlorinated biphenyls
      (PCBs) and polybrominated diphenyl ethers (PBDEs) in Taizhou of Zhejiang
      Province, China. The aims of this study were to assess dual body burdens of the
      two pollutants and potential health risk for local residents. Blood samples were
      collected from two e-waste recycling sites, Luqiao (where PCBs-containing e
      wastes were recycled) and Wenling (where PBDEs-containing e-wastes were
      recycled). The mean summation SigmaPCBs (CB-105, 118, 153, 183, and 180) and
      summation SigmaPBDEs (BDE-28, 47, 99, 100, 153, 154, 180, and 209) were 204.20
      and 117.58 ng g(-1) lipid in the blood from Luqiao, respectively, while they were
      83.80 and 357.44 ng g(-1) lipid from Wenling, respectively. The PCBs levels among
      Luqiao residents were comparable to the values reported for US populations, while
      the PBDEs levels among two study populations were higher than the values from US
      populations. This is the first report to present dual body burdens of PCBs and
      PBDEs at so high levels. Based on previous epidemiologic data, it is suggested
      that dual burdens of PCBs and PBDEs at so high levels might pose health risk for
      local residents. In addition, no correlation between PCBs or PBDEs concentrations
      and the ages of the volunteers was observed in the two populations, which was
      explained by similar exposure time. No correlation of PBDEs with PCBs
      concentrations suggested different pathways of human exposures to PCBs and PBDEs.
      Our findings have raised concern about human health risk of dual exposure to PCBs
      and PBDEs resulting from e-waste recycling.

PMID- 20053419
TI  - Two new hominin cranial fragments from the Mousterian levels at La Quina
      (Charente, France).

PMID- 20053420
TI  - Quantile regression of indoor air concentrations of volatile organic compounds
      (VOC).
AB  - There are many factors determining the concentration of volatile organic
      compounds (VOCs) in indoor air. On the basis of 601 population-based measurements
      we develop an explicit exposure model that includes factors, such as renovation,
      furniture, flat size, smoking, and education level of the occupants. As a novel
      method for the evaluation of concentrations of indoor air pollutants we use
      quantile regression, which has the advantages of robustness against non-Gaussian
      distributions (and outliers) and can adjust for unbalanced frequencies of
      observations. The applied bi- and multivariate quantile regressions provide (1)
      the VOC burden that is representative for the population of Leipzig, Germany, and
      (2) an inter-comparison of the effects of the studied factors and their levels.
      As a result, we find strong evidence for factors of general impact on most VOC
      components, such as the season, flooring, the type of the room, and the size of
      the apartment. Other impact factors are very specific to the VOC components. For
      example, wooden flooring (parquet) and new furniture increase the concentration
      of terpenes as well as the modifying factors high education and sampling in the
      child's room. Smokers ventilate their flats in an extent that in general reduces
      the VOC concentrations, except for benzene (contained in tobacco smoke), which is
      still higher in smoking than in non-smoking flats. Very often dampness is
      associated with an increased VOC burden in indoor air. An investigation of
      mixtures emphasises a high burden of co-occurring terpenes in very small and very
      large apartments.

PMID- 20053421
TI  - Occurrence of synthetic musks in Korean sewage sludges.
AB  - Six polycyclic musks (PCMs) and five nitro musks (NMs) were analyzed in dewatered
      sludge samples from 13 municipal, 4 livestock and 1 pharmaceutical wastewater
      treatment plants (WWTPs) in South Korea. 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8
      hexamethylcyclopenta-(g)-2-benzopyran (HHCB; Galaxolide), Abbalide), and 7-acetyl
      1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN; Tonalide, Fixolide)
      were the two predominant PCMs in the sludge samples, at concentrations ranging
      from 0.52 to 82.0mg/kg dry weight (dw) and 0.12 to 28.8mg/kg (dw), respectively,
      suggesting the extensive use of these two PCMs in South Korea. Hierarchical
      cluster analysis (HCA) revealed the different usage patterns of PCMs between
      livestock cultivating farm and household. The levels of HHCB and AHTN in the
      effluent discharged from the WWTPs were lower than the threshold effect levels
      derived for fish, suggesting low potential risks to aquatic organisms.
      Nevertheless, the calculated discharge of synthetic musks (SMs) from sludge in
      each target WWTP ranged from 36 to 10,961g/d. These results indicate the
      necessity of conducting monitoring studies in marine ecosystems due to ocean
      disposal of sludge, particularly focused on the two prevailing PCMs.

PMID- 20053422
TI  - Uncertainties in critical loads and target loads of sulphur and nitrogen for
      European forests: analysis and quantification.
AB  - An analysis of the uncertainties in critical loads and target loads of sulphur
      (S) and nitrogen (N) for 182 European forest soils was carried out using the Very
      Simple Dynamic (VSD) model. The VSD model was calibrated with a Bayesian approach
      using prior probability functions for model parameters based on literature data,
      data from 200 Dutch forest sites and from simulated denitrification rates from a
      detailed ecosystem model. The calibration strongly improved the fit of the model
      to observed soil and soil solution concentrations, especially for pH and base
      saturation. Calibration also narrowed down the ranges in input parameters. The
      uncertainty analysis showed which parameters contribute most to the uncertainty
      in the critical loads and target loads. Base cation weathering and deposition and
      the parameters describing the H-Al equilibrium in the soil solution determine the
      uncertainty in the maximum critical loads for S, CL(max)(S), when based on the
      aluminium to base cation (Al/Bc) criterion. Uncertainty in CL(max)(S) based on an
      acid neutralizing capacity (ANC) criterion is completely determined by base
      cation inputs alone. The denitrification fraction is the most important source of
      uncertainty for the maximum critical loads of N, CL(max)(N). N uptake and N
      immobilisation determine the uncertainties in the critical load for N as a
      nutrient, CL(nut)(N). Calibration of VSD reduced the uncertainty: the coefficient
      of variation (CV) was reduced for all critical loads and criteria. After
      calibration, the CV for CL(max)(S) was below 0.4 for almost all plots; however
      for CL(max)(N) high values occurred for plots with high denitrification rates.
      Model calibration also improved the robustness of target load estimates: after
      calibration, no target loads were needed in any of the simulations for 40% of the
      plots, with the uncalibrated model there was a positive probability for the need
      of a target load for almost all plots.

PMID- 20053423
TI  - Monocyte-platelet aggregates and platelet micro-particles in patients with post
      hepatitic liver cirrhosis.
AB  - INTRODUCTION: Monocytes are the cells that play a crucial role in the
      pathogenesis of liver damage and liver cirrhosis (LC), and as platelets, by
      connecting hemostasis and inflammatory processes, participate in pathogenesis of
      chronic liver diseases, we aimed to investigate the presence of monocyte-platelet
      aggregates and platelet micro-particles (PMPs) and their role in LC. PATIENTS AND
      METHODS: The study included 60 patients with post-hepatitic LC and 20 healthy
      controls. Activated monocytes (CD11b, HLA-DR, CD14, CD16), monocyte-platelet
      aggregates (CD41/CD14), activated platelets (CD41/CD62) and PMPs were analyzed by
      flow cytometry. Their relations to the clinical and laboratory data were assessed
      in the studied group. RESULTS: Patients with LC had higher levels of activated
      platelets, activated monocytes and monocyte-platelet aggregations as compared to
      healthy controls. PMPs percentage showed no significant differences between
      patients and controls but significantly increased in both patients with no
      bleeding and patients with splenomegaly compared to patients without. All studied
      markers showed no significant differences between patients with thrombocytopenia
      and those with normal platelet counts and also between patients with different
      disease stages. Positive correlations between monocyte-platelet aggregates and
      both activated platelets and monocytes were demonstrated. There were significant
      negative correlations between PMPs and both age and prothrombin time among
      patients. CONCLUSIONS: The stage of post-hepatitic LC is not the only factor that
      affects the level of activated platelets, activated monocytes and monocyte
      platelet aggregates. PMPs have no influence on thrombocytopenia but may have the
      potential to influence the progression of clotting activity in LC.

PMID- 20053424
TI  - Long-term stability of fibrinolytic factors stored at -80 degrees C.
AB  - INTRODUCTION: Blood samples in epidemiological studies are often stored for
      several years and analysed at different occasions. The reagent kits are
      continually modified for better precision and accuracy. Our hypothesis was that
      epidemiological studies are affected by long-term storage and/or modifications of
      reagent kits. MATERIALS AND METHODS: Plasma samples stored at -80( degrees )C
      from two populations were used: A case-referent study with samples collected from
      1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term
      storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001
      (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications.
      Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex
      and chromogenic substrate assays of the activities of tPA and PAI-1. RESULTS:
      Long-term storage for a median time of 11.6 years (range 5 to 20) showed an
      effect of time on tPA antigen R(2)=0.01, PAI-1 antigen R(2)=0.01 and tPA-PAI-1
      complex R(2) = 0.02. Modifications in reagent kits affected the levels of
      fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72
      and 0.95 (R(2) 0.47 - 0.75), whereas tPA activity showed an agreement with slope
      coefficients 1.06 to 1.09 (R(2) 0.67 - 0.93). CONCLUSIONS: This study showed that
      long-term storage affects fibrinolytic variables to a negligible extent, but
      modifications in reagent kits introduced an element of bias. We conclude that
      analysis of samples on a single occasion is preferable to multiple occasions, as
      storage has negligible effect.

PMID- 20053425
TI  - Whole blood impedance aggregometry detects heparin-induced thrombocytopenia
      antibodies.
AB  - Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin use.
      IgG antibodies to complexes of platelet factor 4 (PF4) and heparin trigger the
      clinical manifestations of HIT. Only a subset of these antibodies will activate
      platelets and these can only be identified with platelet aggregation (functional)
      assays. Heparin-induced platelet aggregation (HIPA) and (14)C-serotonin release
      (SRA) assays for HIT are time-consuming and complex to perform. We have developed
      a whole blood impedance (WBI) test using the new Multiplate analyser. All samples
      referred to our laboratory over a 10 month period were screened for heparin-PF4
      antibodies by an ELISA method (Zymutest HIA IgG). The 4T's score was used to
      assess HIT pretest probability. Twenty antibody positive samples were further
      tested by all three functional assays: light transmission aggregometry (LTA), SRA
      and WBI. Thirteen out of twenty samples were positive by LTA (10 patients) and 15
      by WBI (11 patients). SRA, considered to be the gold standard, was used as a
      confirmatory test and 11 were found to be positive (10 patients); four discrepant
      samples were weakly positive by WBI. The prevalence of a positive functional test
      was strongly correlated with the 4T's clinical risk score, but a small number of
      low-risk patients had positive functional assays. In this study, the WBI assay
      detected all SRA positive patients and was positive for two others suggesting
      greater sensitivity. The rapid and easy to perform assay may be a useful tool for
      haematology laboratories to detect platelet-activating HIT antibodies.

PMID- 20053426
TI  - Peri-procedural anticoagulation in patients undergoing ablation for atrial
      fibrillation.
AB  - Radiofrequency catheter ablation is being used with increasing frequency as a
      strategy to manage atrial fibrillation. Patients undergoing this procedure are at
      increased short-term risk of thromboembolism for several days and up to 4 weeks
      or longer after their ablation, and anticoagulation management surrounding the
      ablation procedure remains controversial. Although no conclusive recommendations
      can be made, published guidelines and data support therapeutic anticoagulation
      with warfarin for 3 weeks prior and intravenous heparin during the ablation.
      Warfarin may either be continued through the ablation or stopped 2-5 days prior.
      If the latter approach is chosen, a pre-ablation bridging strategy of enoxaparin
      1mg/kg twice daily is reasonable in selected patients unless the patient's
      bleeding risk dictates using a lower dose regimen (0.5mg/kg twice daily) or
      avoiding bridging altogether. Fewer data are available for post-ablation
      management strategies, and current practice patterns are based largely on single
      center experiences in smaller, non-randomized studies. For lower risk patients
      (CHADS(2) 0-1), either warfarin or aspirin may be utilized without bridging. In
      higher thromboembolic risk patients (CHADS(2) >or=2), either enoxaparin (1mg/kg
      twice daily) or heparin may be started within the first 12-24h post-procedure.
      For patients with bleeding risk factors, enoxaparin may be subsequently reduced
      to 0.5mg/kg until the INR is therapeutic, although the efficacy of this lower
      dosing regimen has not been well studied. In accordance with national guidelines,
      warfarin should be continued post-ablation for a minimum of 2 months and then
      indefinitely in patients with a CHADS(2) score >or= 2.

PMID- 20053427
TI  - Lectin binding in normal, keratoconus and cross-linked human corneas.
AB  - In this study the characterization of various types of sugar residues in normal,
      keratoconus and cross-linked human corneas was performed using
      immunohistochemical localization with lectins. Corneal samples were collected and
      divided into three groups: (1) normal corneas from cadavers; (2) keratoconic
      corneal buttons; (3) keratoconic corneal buttons treated with cross-linking. A
      series of lectins including: DBA, SBA, PNA, ConA, WGA, UEA I, GNA, DSA, MAA, SNA,
      were used in combination with chemical and enzymatic treatments. Compared with
      the normal corneas, N-acetyl-D-glucosamine increased in the keratoconus corneas.
      L-fucose increased and/or appeared in the keratoconus and the cross-linked
      corneas. N-acetyl-D-galactosamine was more abundant in the epithelium of
      keratoconus corneas, but was lacking in the keratoconus and cross-linked
      endothelium. D-galactose-(beta1-4)-N-acetyl-D-glucosamine was absent in the whole
      stroma of the keratoconus corneas and in the deep layers of the cross-linked
      ones. Sialic acids increased in the keratoconus corneas and decreased in the
      cross-linked ones. These results showed altered glycosylation in the keratoconic
      corneas and partially similar glycosylation in the cross-linked corneas, compared
      to the normal ones. This suggests a role played by sugar residues in maintaining
      the corneal structure. The changes could be related to structural alterations in
      keratoconus. The present findings contribute to our understanding of the effect
      of cross-linking treatment of keratoconic corneas in therapeutic attempts to re
      establish the normal corneal structure.

PMID- 20053428
TI  - In vivo development of vitrified rabbit embryos: effects on prenatal survival and
      placental development.
AB  - The aim of this work is to study the effect of the vitrification procedure on
      prenatal survival and on placental development at the end of gestation in rabbits
      (Oryctolagus cuniculus). One hundred eighty-one females were slaughtered at 72 h
      of gestation. Morphologically normal embryos recovered at 72 h of gestation were
      kept at room temperature until transfer or vitrification. Vitrified embryos (320
      embryos) were transferred into a total of 24 does and fresh embryos (712 embryos)
      were transferred into a total of 43 does. Females were induced to ovulate 72 h
      before transfer when fresh embryos were transferred and 60 to 63 h before
      transfer when vitrified embryos were transferred. Each recipient doe received
      eight embryos into the left oviduct and eight embryos into the right oviduct. The
      number of implanted embryos was estimated by laparoscopy as number of
      implantation sites at Day 14 of gestation. Recipient females were slaughtered by
      stunning and exsanguination 25 d after the transfer, and fetuses were classified
      according to their status. Live fetuses and fetal and maternal placenta were
      weighed Pregnancy rate was defined as the total number of females having at least
      one live fetus at Day 28 of gestation divided by the total number of females.
      Prenatal survival was estimated as live fetuses at Day 28 of gestation divided by
      the number of transferred embryos. The pregnancy rate after transfer of vitrified
      embryos (92%) was similar to that achieved with fresh embryos (86%), but prenatal
      survival was lower for vitrified than for fresh embryos (53% vs. 34%). We did not
      find differences in embryo survival from 72 h to implantation. Transfer of
      vitrified embryos reduced fetal survival from implantation to Day 28 (57% vs.
      82%). Differences in the number of live fetuses at Day 28 of gestation were
      mainly due to the higher fetal mortality observed soon after implantation in
      pregnancies resulting from the transfer of vitrified embryos. A higher percentage
      of decidual reactions and atrophic maternal placentas (27.5% vs. 8.3%) and also
      of atrophic fetal and maternal placentas (12.1% vs. 5.3%) were observed after
      transfer of vitrified embryos. Both treatments showed similar percentage of dead
      fetuses (3.3% vs. 4%). Maternal placenta of the fetuses from fresh embryos was
      15% heavier than maternal placenta of fetuses from vitrified embryos.

PMID- 20053429
TI  - Embryo production in superovulated Angus cows inseminated four times with sexed
      sorted or conventional, frozen-thawed semen.
AB  - This study tested the hypothesis that four inseminations of commercially frozen
      sexed semen (>or=2.1x10(6) sperm per 0.25-mL straw) in superstimulated embryo
      donors would yield a percentage and quantity of transferable embryos similar to
      that achieved with conventional frozen semen. Bos taurus, angus cows (n=32),
      stratified by age and body condition, were randomly allocated to receive four
      inseminations of frozen-thawed semen, either conventional semen (>or=15x10(6)
      sperm/straw; Conventional) or sexed semen (>or=2.1x10(6) sperm/straw; Sexed) from
      one of two AI sires. From 10 to 13 d after estrus, follicle-stimulating hormone
      (FSH) was given twice-daily, with prostaglandin F(2alpha) given twice on the last
      day. Cows were inseminated once (1x) at first detected estrus and twice (2x) and
      once (1x) at 12 and 24h later, respectively, with nonsurgical embryo recovery 7 d
      after first detected estrus. The study was repeated 30 d later (switch-back
      experimental design). The total number of ova per flush was similar between
      Conventional and Sexed treatments (10.9+/-1.8 vs. 10.5+/-1.6), but the number of
      Grade 1 embryos was greater (P<0.01) for Conventional (4.3+/-0.8 vs. 2.3+/-0.7).
      Conversely, the mean number of unfertilized ova was greater (P<0.05) for Sexed
      (5.6+/-1.0 vs. 3.0+/-1.2). There was no significant difference between treatments
      for numbers of degenerate, Grades 2 or 3, and transferable embryos and no
      significant differences between bulls in percentage of transferable embryos
      (44.4% and 46.7%). However, fertilization rates and percentage of transferable
      embryos were affected (P<0.05) by period and donor. In conclusion,
      superstimulated donor cows inseminated four times had fewer Grade 1 embryos and
      more unfertilized ova with sexed versus conventional semen.

PMID- 20053430
TI  - Production of dairy goat embryos, by nuclear transfer, transgenic for human acid
      beta-glucosidase.
AB  - Expression of recombinant human lysosomal acid beta-glucosidase (hGCase) by a
      transgenic animal bioreactor, using somatic cell nuclear transfer (SCNT), would
      decrease the cost of producing this product. The objective was to establish an
      effective procedure to prepare hGCase transgenic donor cells and nuclear transfer
      (NT) embryos to produce hGCase protein in the Saanen dairy goat mammary gland. A
      mammary-specific expression vector for hGCase was constructed and transfected
      into HC-11 mammary epithelial cells for bioactivity analysis in vitro; mRNA
      transcripts and hGCase protein were correctly expressed in transfected HC-11
      cells. The hGCase gene was then introduced into fetal fibroblasts (from dairy
      goats) to prepare competent transgenic donor cells. Transgenic fibroblast clones
      from a single round of transfection were reliably isolated by 96-well cell
      culture plates and screened with PCR amplification and chromosomal counting
      (66.8%). Dairy goat cloned embryos were produced from these hGCase fetal cells by
      SCNT, the hGCase transgene was successfully detected in these embryos, and there
      were similar rates (P>0.05) of fusion (83.3% vs. 77.8%), cleavage (89.1% vs.
      90.9%), and development to the morula/blastocyst stages (36.4% vs. 38.9%) between
      NT embryos using transgenic fetal fibroblasts and non-transfected control cells.
      Moreover, 98 well-developed reconstructed embryos derived from transgenic cells
      were transferred to 16 recipients; pregnancy was confirmed at 40 d in two goats.
      Therefore, we achieved functional expression of hGCase in mammary gland cells and
      normal development to Day 40 of cloned embryos carrying the hGCase gene.

PMID- 20053431
TI  - Individual differences in auditory sentence comprehension in children: An
      exploratory event-related functional magnetic resonance imaging investigation.
AB  - The purpose of this study was to explore changes in activation of the cortical
      network that serves auditory sentence comprehension in children in response to
      increasing demands of complex sentences. A further goal is to study how
      individual differences in children's receptive language abilities are associated
      with such changes in cortical responses. Fourteen children, 10-16 years old,
      participated in an event-related functional magnetic resonance imaging experiment
      using a cross modal sentence-picture verification paradigm. We manipulated
      sentence difficulty and length in a 2x2 factorial design. Task-related activation
      covered large regions of the left and right superior temporal cortex, inferior
      parietal lobe, precuneous, cingulate, middle frontal gyrus and precentral gyrus.
      Sentence difficulty, independent of length, led to increased activation in the
      left temporal-parietal junction and right superior temporal gyrus. Changes in
      activation in frontal regions positively correlated with age-standardized
      receptive vocabulary scores and negatively correlated with reaction time on a
      receptive grammar test outside the scanner. Thus, individual differences in
      language skills were associated with changes in the network in response to
      changing task demands. These preliminary findings in a small sample of typically
      developing children suggest that the investigation of individual differences may
      prove useful in elucidating the underlying neural mechanisms of language
      disorders in children.

PMID- 20053432
TI  - Relationship between mechanical properties of one-step self-etch adhesives and
      water sorption.
AB  - OBJECTIVES: The purpose of this study was to evaluate the relationship between
      changes in the modulus of elasticity and ultimate tensile strength of one-step
      self-etch adhesives, and their degree of water sorption. METHODS: Five one-step
      self-etch adhesives, Xeno IV (Dentsply Caulk), G Bond (GC Corp.), Clearfil S3
      Bond (Kuraray Medical Inc.), Bond Force (Tokuyama Dental Corp.), and One-Up Bond
      F Plus (Tokuyama Dental Corp.) were used. Ten dumbelled-shaped polymers of each
      adhesive were used to obtain the modulus of elasticity by the three-point
      flexural bending test and the ultimate tensile strength by microtensile testing.
      The modulus of elasticity and the ultimate tensile strength were measured in both
      dry and wet conditions before/after immersion in water for 24h. Water sorption
      was measured, using a modification of the ISO-4049 standard. Each result of the
      modulus of elasticity and ultimate tensile strength was statistically analyzed
      using a two-way ANOVA and the result of water sorption was statistically analyzed
      using a one-way ANOVA. Regression analyses were used to determine the
      correlations between the modulus of elasticity and the ultimate tensile strength
      in dry or wet states, and also the percent decrease in these properties
      before/after immersion of water vs. water sorption. RESULTS: In the dry state,
      the moduli of elasticity of the five adhesive polymers varied from 948 to 1530
      MPa, while the ultimate tensile strengths varied from 24.4 to 61.5 MPa. The wet
      specimens gave much lower moduli of elasticity (from 584 to 1073 MPa) and
      ultimate tensile strengths (from 16.5 to 35.0 MPa). Water sorption varied from
      32.1 to 105.8 g mm(-3). SIGNIFICANCE: The moduli of elasticity and ultimate
      tensile strengths of the adhesives fell significantly after water-storage. Water
      sorption depended on the constituents of the adhesive systems. The percent
      decreases in the ultimate tensile strengths of the adhesives were related to
      water sorption, while the percent reductions in the moduli of elasticity of the
      adhesives were not related to water sorption.

PMID- 20053433
TI  - Relationship between bond strength tests and other in vitro phenomena.
AB  - OBJECTIVES: The objective of this manuscript is to outline the relationship
      between bond strength tests of adhesive materials and other in vitro phenomena by
      reviewing the literature generated over the thirty years. METHODS: Information
      was gathered from nearly 30 published articles appearing in dental literature.
      Studies were predominantly identified through a search of the PubMED database
      with a few additional studies published in Japanese domestic journals. RESULTS:
      Studies were included that provided evidence for the relationship between results
      of evaluations of the bond strengths and other in vitro phenomena such as micro
      leakage, nanoleakage, structural of bonding interface and mechanical properties
      of bonding interface. An attempt was made to select articles that spanned the
      timeframe from approximately 1980 to today to try to ensure that the classic
      literature as well as the latest information was included. CONCLUSIONS: Previous
      studies have indicated bond strength did not correlate with the results of micro
      leakage tests nor gap formation at the cavity margin. The nanoleakage test and
      morphological and chemical characteristics of the bonding interface had potential
      to predict the dentin bond durability. SIGNIFICANCE: Bond strength test results
      and other in vitro phenomena was not evenly correlated. According to the
      development of the materials, the most appropriate bond test and analysis of the
      in vitro phenomena should be also developed.

PMID- 20053434
TI  - Physical properties of a new silorane-based restorative system.
AB  - OBJECTIVES: To distinguish the physical properties of a new silorane-based
      restorative material in comparison to five methacrylate-based restorative
      materials--a compomer, giomer, nanocomposite, hybrid and micro-hybrid. METHODS:
      The following properties were examined per restorative material: compressive
      strength, diametral tensile strength, flexural strength/modulus, fracture
      toughness, microhardness, and polymerization shrinkage. The mean and standard
      deviation were determined per group. A one-way ANOVA/Tukey was performed per
      property (alpha=0.05). RESULTS: Significant differences were found between groups
      per property (p<0.001). CONCLUSIONS: Compared to the methacrylate-based
      restorative materials, the new silorane-based material had the lowest
      polymerization shrinkage, but an overall mixed mechanical performance. The
      silorane-based material had relatively higher flexural strength/modulus, fracture
      toughness, but relatively lower compressive strength and microhardness than the
      methacrylate-based restorative materials.

PMID- 20053435
TI  - The intracellular drug delivery and anti tumor activity of doxorubicin loaded
      poly(gamma-benzyl L-glutamate)-b-hyaluronan polymersomes.
AB  - We have investigated the intracellular delivery of doxorubicin (DOX) loaded
      poly(gamma-benzyl L-glutamate)-block-hyaluronan (PBLG-b-HYA) based polymersomes
      (PolyDOX) in high (MCF-7) and low (U87) CD44 expressing cancer cell models. DOX
      was successfully loaded into polymersomes using nanoprecipitation method and in
      vitro drug release pattern were achieved at pH 5.5 and 7.4 up to 10 days. Block
      copolymer vesicles without loaded DOX were non cytotoxic in both cells at
      concentration 150-650 microg/mL. Flow cytometry data suggested successful uptake
      of PolyDOX in cells and high accumulation was found in MCF-7 than U87 cells.
      Microscopy imagings revealed that in MCF-7 cells PolyDOX was more in cytoplasm
      and free DOX in nuclei, whereas in U87 cells free DOX was also found in the
      cytoplasm. Cytotoxicity of the drug was concentration and exposure time
      dependent. In addition, PolyDOX significantly enhanced reactive oxygen species
      (ROS) level in both cells. PolyDOX also suppressed growth of breast tumor on
      female Sprague-Dawley (SD) rats as compared to phosphate buffer saline pH 7.4
      (PBS) control group. In addition reduced level of serum enzymes (LDH and CPK) by
      PolyDOX formulation indicated less cardiotoxicity of DOX after loading in
      polymersomes. Results suggest that intracellular delivery of PolyDOX was depended
      on the CD44 expression level in cells due to presence of hyaluronic acid on the
      surface of polymersomes, and could be used as a self-targeting drug delivery
      cargo in over-expressed CD44 glycoprotein cells of breast cancer.

PMID- 20053436
TI  - Direct and indirect effects of microstructured titanium substrates on the
      induction of mesenchymal stem cell differentiation towards the osteoblast
      lineage.
AB  - Microstructured and high surface energy titanium substrates increase
      osseointegration in vivo. In vitro, osteoblast differentiation is increased, but
      effects of the surface directly on multipotent mesenchymal stem cells (MSCs) and
      consequences for MSCs in the peri-implant environment are not known. We evaluated
      responses of human MSCs to substrate surface properties and examined the
      underlying mechanisms involved. MSCs exhibited osteoblast characteristics
      (alkaline phosphatase, RUNX2, and osteocalcin) when grown on microstructured Ti;
      this effect was more robust with increased hydrophilicity. Factors produced by
      osteoblasts grown on microstructured Ti were sufficient to induce co-cultured MSC
      differentiation to osteoblasts. Silencing studies showed that this was due to
      signaling via alpha2beta1 integrins in osteoblasts on the substrate surface and
      paracrine action of secreted Dkk2. Thus, human MSCs are sensitive to substrate
      properties that induce osteoblastic differentiation; osteoblasts interact with
      these surface properties via alpha2beta1 and secrete Dkk2, which acts on distal
      MSCs.

PMID- 20053437
TI  - Genome-wide pathways analysis of nickel ion-induced differential genes expression
      in fibroblasts.
AB  - To reveal molecular mechanisms of the interaction between Ni2+ and cells, cDNA
      microarray technology and GenMAPP analysis were utilized to investigate changes
      of gene expression profile and identify significant biological pathways in mouse
      fibroblast cells (L-929) treated by 100 microm Ni2+ for 12, 24, 48 and 72 h,
      respectively. The microarray data was validated by real-time PCR.
      Methylthiazoltetrazolium (MTT) analysis and flow cytometry experiment were used
      to assess the cellular response of L-929 cells to Ni2+. It was found that six
      main biological pathways were affected by Ni2+ with 118 differentially expressed
      genes involved. Further analysis illuminated that the exposure of cells to Ni2+
      may evoke series of cellular responses to hypoxia by regulating hypoxia-inducible
      gene expression and cause irreversible DNA damage. Cell cycle pathway analysis
      results showed DNA replication in S phase could be inhibited by Ni2+ which was
      consistent with the data gained from flow cytometry experiment. Compared to
      previous researches based on conventional molecular biology experiments, the
      present work has not only indirectly validated the findings of other groups but
      also obtained several discoveries related to cell-Ni2+ interaction, such as
      inhibition of electron transport chain and accumulation of extracellular matrix
      (ECM) collagens. The routine of the present study not only can analyze gene
      expression profile but also may provide a more convenient and efficient approach
      to explain molecular mechanisms of cell-biomaterial interaction.

PMID- 20053438
TI  - Repair of meniscal cartilage white zone tears using a stem cell/collagen-scaffold
      implant.
AB  - Injuries to the avascular region of knee meniscal cartilage do not heal
      spontaneously. To address this problem we have developed a new stem cell/collagen
      scaffold implant system in which human adult bone marrow mesenchymal stem cells
      are seeded onto a biodegradable scaffold that allows controlled delivery of
      actively dividing cells to the meniscus surface. Sandwich constructs of two white
      zone ovine meniscus discs with stem cell/collagen-scaffold implant in between
      were cultured in vitro for 40 days. Histomorphometric analysis revealed superior
      integration in the stem cell/collagen-scaffold groups compared to the cell-free
      collagen membrane or untreated controls. The addition of TGF-beta1 to
      differentiate stem cells to chondrocytes inhibited integration. Biomechanical
      testing demonstrated a significant 2-fold increase in tensile strength in all
      constructs using the stem cell/collagen-scaffold compared to control groups after
      40 days in culture. Integration was significantly higher when collagen membranes
      were used that had a more open/spongy structure adjacent to both meniscal
      cartilage surfaces, whereas a collagen scaffold designed for osteoinduction
      failed to induce any integration of meniscus. In conclusion, the stem
      cell/collagen-scaffold implant is a potential therapeutic treatment for the
      repair of white zone meniscal cartilage tears.

PMID- 20053439
TI  - In vitro and in vivo evaluation of an alumina-zirconia composite for arthroplasty
      applications.
AB  - In order to improve the reliability and the mechanical properties of orthopaedic
      hip prosthesis, new ceramic composites starting with nanosized powders of alumina
      and zirconia have been recently developed. The aim of the present study was to
      investigate the biological tolerance of one of these sintered ceramics and of its
      alumina and zirconia constitutive nanosized powders with both in vitro and in
      vivo approaches. At first, osteoblasts and fibroblasts were cultured either upon
      sintered ceramic discs with polished or rough surfaces or in the presence of the
      corresponding alumina or zirconia powders at various concentrations. Thereafter,
      we chronically injected these powders in the knee articulation of rats. In vitro,
      the materials showed no deleterious effect on cell proliferation, extra-cellular
      matrix production (human type I collagen and fibronectin) or on cell morphology.
      In vivo, the histological examination showed only a very moderate and non
      specific granulomatous response of the synovial membrane but no major
      inflammation as clinically described with metals or polyethylene wear debris.
      Besides its improved physical properties, this recently developed alumina
      zirconia composite showed satisfactory biocompatibility.

PMID- 20053440
TI  - Cu2+-labeled, SPION loaded porous silica nanoparticles for cell labeling and
      multifunctional imaging probes.
AB  - We have developed an ion-sensing nanoparticle that is comprised of a
      superparamagnetic iron oxide (SPIO) core encapsulated with a porous silica shell.
      The latter can be readily anchored with ligands capable of coordinating with
      positron-emitting metal. Evidently, this nanoparticle has a great potential for
      use in cell tracking with magnetic resonance (MR) imaging and positron emission
      tomography (PET). Herein we report the synthesis, surface functionalization and
      characterization of the magnetic nanoparticle-based probes and evaluate their
      cell-labeling efficacy, cytotoxicity and relaxivity in comparison to one of the
      most commonly utilized MRI contrast agents, Feridex.

PMID- 20053441
TI  - The effect of scaffold composition on the early structural characteristics of
      chondrocytes and expression of adhesion molecules.
AB  - Previously we demonstrated that chondrocyte ECM synthesis and mitotic activity
      was dependent on scaffold composition when cultured on uncoated PCL scaffolds
      (pPCL) or PCL composites containing hyaluronan (PCL/HA), chitosan (PCL/CS),
      fibrin (PCL/F), or collagen type I (PCL/COL1). We hypothesized that initial cell
      contact with these biomaterials results in ultrastructural changes and alters
      CD44 and integrin beta1 expression. The current study was designed to investigate
      the early ultrastructural responses of chondrocytes on these scaffolds and
      expression of CD44 and integrin beta1. A common observation 1 h after seeding was
      the abundance of cell processes. Different types of cell processes occurred in
      different areas of the same cell and on different cells within the same
      composite. Chondrocytes seeded onto PCL/CS had the greatest cell surface
      enhancement. PCL/HA promoted CD44 expression and almost spherical cells with a
      low degree of surface enhancement. PCL/COL1 enabled continuing expression of
      integrin beta1 and CD44. In contrast, cells in PCL/CS, PCL/F and pPCL promoted
      elliptic cells with a higher degree of surface enhancement and no prolonged CD44
      and integrin beta1 expression. A strong variability of cell surface processes
      indicated either reparative or degenerative adaptation to the artificial
      environment. Interestingly, we found initial integrin beta1 expression in all
      composite scaffolds, but not in pPCL although this promoted strong adhesiveness
      as indicated by the formation of stress fibers. In conclusion, chondrocytes
      respond to biomaterials early after implantation by altering ultrastructural
      characteristics and expression of CD44 and integrin beta1.

PMID- 20053442
TI  - The performance of photooxidatively crosslinked acellular bovine jugular vein
      conduits in the reconstruction of connections between pulmonary arteries and
      right ventricles.
AB  - In this study, valved photooxidatively crosslinked acellular bovine jugular vein
      conduits (BJVCs) were implanted in young dogs to reconstruct the connections of
      pulmonary arteries and right ventricles, with acellular conduits used as
      controls. All acellular conduits had moderate to severe valvular dysfunction and
      were explanted at 1-month implantation (n = 5). Histological examination showed
      inflammatory cell infiltration and intimal hyperplasia in the walls, and severe
      inflammatory cell infiltration and thrombosis in the valves. The photooxidatively
      crosslinked acellular conduits were retrieved at 1-month (n = 5) and 6-month (n =
      5) implantations respectively. These conduits had excellent valvular function at
      retrieval. Their walls and valves were still soft and smooth without
      calcification and hemangioma. Endothelialization in valves and luminal walls was
      unsatisfied at 1-month retrieval, and was improved at 6-month retrieval. Host
      cells infiltrated and migrated from outer layer to the middle layer, with tissue
      remolding and regeneration found in these recellular regions. Histological
      examination and tissue content assay demonstrated that degeneration and
      regeneration of collagens and glycosaminoglycans were comparable, but elastic
      fibers gradually degraded. Photooxidatively crosslinked acellular BJVCs resist
      calcification and thrombosis and have regeneration patterns, with excellent
      hemodynamic performance.

PMID- 20053443
TI  - The effect of unlocking RGD-motifs in collagen I on pre-osteoblast adhesion and
      differentiation.
AB  - Denaturation of extracellular matrix proteins exposes cryptic binding sites. It
      is hypothesized that binding of cell adhesion receptors to these cryptic binding
      sites regulates cellular behaviour during tissue repair and regeneration. To test
      this hypothesis, we quantify the adhesion of pre-osteoblastic cells to native
      (Col) and partially-denatured (pdCol) collagen I using single-cell force
      spectroscopy. During early stages of cell attachment (< or =180 s) pre
      osteoblasts (MC3T3-E1) adhered significantly stronger to pdCol compared to Col.
      RGD (Arg-Gly-Asp)-containing peptides suppressed this elevated cell adhesion. We
      show that the RGD-binding alpha(5)beta(1)- and alpha(v)-integrins mediated pre
      osteoblast adhesion to pdCol, but not to Col. On pdCol pre-osteoblasts had a
      higher focal adhesion kinase tyrosine-phosphorylation level that correlated with
      enhanced spreading and motility. Moreover, pre-osteoblasts cultured on pdCol
      showed a pronounced matrix mineralization activity. Our data suggest that
      partially-denatured collagen exposes RGD-motifs that trigger binding of
      alpha(5)beta(1)- and alpha(v)-integrins. These integrins initiate cellular
      processes that stimulate osteoblast adhesion, spreading, motility and
      differentiation. Taken together, these quantitative insights reveal an approach
      for the development of alternative collagen I- based surfaces for tissue
      engineering applications.

PMID- 20053444
TI  - Peptide-conjugated biodegradable nanoparticles as a carrier to target paclitaxel
      to tumor neovasculature.
AB  - Antiangiogenic cancer therapy can be achieved through the targeted delivery of
      antiangiogenic agents to the endothelial cells of tumor neovasculature. In the
      present study, we developed a drug delivery system (DDS), nanoparticles
      conjugated with K237-(HTMYYHHYQHHL) peptides for tumor neovasculature targeting
      drug delivery. Paclitaxel, a chemotherapeutic agent with potent antiangiogenic
      activity, was used as a prototype drug. We synthesized the aldehyde poly(ethylene
      glycol)-poly(lactide) (aldehyde-PEG-PLA) block copolymer by ring opening
      polymerization. The nanoparticles loading paclitaxel (PTX-NP) were fabricated
      using the O/W emulsion and evaporation technique. K237 ligand, a peptide that can
      bind to the KDR receptors predominantly expressed on the surface of tumor
      neovasculature endothelial cells with high affinity and specificity and inhibit
      the VEGF-KDR angiogenic signal pathway, was conjugated to the aldehyde group of
      PEG chain using the N-terminal PEGylation technique. The K237 conjugated
      paclitaxel-loaded nanoparticles (K237-PTX-NP) had a hydrodynamic diameter of 150
      nm. The K237 density on nanoparticle surface was 474 and the mean distance
      between two neighboring PEG chains linked to K237 peptide was 12 nm. The K237
      conjugated nanoparticles could be significantly internalized by human umbilical
      vein endothelial cells (HUVEC) through the K237-KDR interaction, and this
      facilitated uptake led to the expected enhanced antiangiogenic activity shown by
      HUVEC proliferation, migration and tube formation compared to cells treated with
      the commercial formulation Taxol and PTX-NP. The long-circulating property and
      the K237 ligand of K237-PTX-NP warranted rapid, long-term, and accurate in vivo
      tumor neovasculature targeting, and thereafter the significant apoptosis of tumor
      neovasculature endothelial cells and necrosis of tumor tissues of MDA-MB-231
      breast tumors implanted in female BLAB/c nude mice. This nanoparticulate DDS
      offers a new strategy for paclitaxel chemotherapy application and it could also
      be used to carry other chemotherapeutic drugs, genes, and proteins with
      antiangiogenic activity for antiangiogenic cancer therapy.

PMID- 20053446
TI  - Calcium homeostasis of acutely denervated and lesioned dentate gyrus in
      organotypic entorhino-hippocampal co-cultures.
AB  - Denervation of neurons, e.g. upon traumatic injury or neuronal degeneration,
      induces transneuronal degenerative events, such as spine loss, dendritic pruning,
      and even cell loss. We studied one possible mechanism proposed to trigger such
      events, i.e. excess glutamate release from severed axons conveyed
      transsynaptically via postsynaptic calcium influx. Using 2-photon microscopical
      calcium imaging in organotypic entorhino-hippocampal co-cultures, we show that
      acute transection of the perforant path elicits two independent effects on
      calcium homeostasis in the dentate gyrus: a brief, short-latency elevation of
      postsynaptic calcium levels in denervated granule cells, which can be blocked by
      preincubation with tetrodotoxin, and a long-latency astroglial calcium wave, not
      blocked by tetrodotoxin and propagating slowly through the hippocampus. While
      neuronal calcium elevations upon axonal transection placed remote from the target
      area were similar to those elicited by brief trains of electrical stimulation of
      the perforant path, large-scale calcium signals were observed upon lesions placed
      close to or within the dendritic field of granule cells. Concordantly, induction
      of c-fos in denervated neurons coincided spatially with cell populations showing
      prolonged calcium elevations upon concomitant dendritic damage. Since denervation
      of dentate granule cells by remote transection of the perforant path induces
      transsynaptic dendritic reorganization in the utilized organotypic cultures, a
      generalized breakdown of the cellular calcium homeostasis is unlikely to underlie
      these transneuronal changes.

PMID- 20053445
TI  - Calcium, cellular aging, and selective neuronal vulnerability in Parkinson's
      disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease in
      developed countries. The core motor symptoms are attributable to the degeneration
      of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Why these
      neurons, and other restricted sets of non-dopamine neuron, succumb in PD is not
      clear. One potential clue has come from the observation that the engagement of L
      type Ca2+ channels during autonomous pacemaking elevates the sensitivity of SNc
      DA neurons to mitochondrial toxins used to create animal models of PD, suggesting
      that Ca2+ entry is a factor in their selective vulnerability. Epidemiological
      data also supports a linkage between L-type Ca2+ channels and the risk of
      developing PD. This review examines the hypothesis that the primary factor
      driving neurodegenerative changes in PD is the metabolic stress created by
      sustained Ca2+ entry, particularly in the face of genetic or environmental
      factors that compromise oxidative defenses or proteostatic competence.

PMID- 20053447
TI  - Aberrant Ca2+ handling in lysosomal storage disorders.
AB  - Lysosomal storage diseases (LSDs) are caused by inability of cells to process the
      material captured during endocytosis. While they are essentially diseases of
      cellular "indigestion", LSDs affect large number of cellular activities and, as
      such, they teach us about the integrative function of the cell, as well as about
      the gaps in our knowledge of the endocytic pathway and membrane transport. The
      present review summarizes recent findings on Ca2+ handling in LSDs and attempts
      to identify the key questions on alterations in Ca2+ signaling and membrane
      transport in this group of diseases, answers to which may lie in delineating the
      cellular pathogeneses of LSDs.

PMID- 20053448
TI  - Severe anemia caused by combination of autoimmune hemolysis, pure red cell
      aplasia and massive bone marrow infiltration in an elderly patient with chronic
      lymphocytic leukemia: successful treatment with rituximab.

PMID- 20053449
TI  - A role for neutrophils in rituximab therapy?

PMID- 20053450
TI  - Exploring novel therapeutic options in T-LGL, including epigenetic modulation: a
      case report.

PMID- 20053451
TI  - [20 years after the Convention on the Rights of the Child, its incorporation into
      the constitutions of Latin America and the jurisprudence of constitutional
      courts].

PMID- 20053452
TI  - Experiences of family maltreatment by Korean children in Korean National
      Protective Services.
AB  - OBJECTIVE: The objective of this study is twofold. The first objective is to
      explore the extent of family maltreatment experiences of children in protective
      care in South Korea. The second objective is to analyze the circumstances around
      the maltreatment and to obtain a better understanding of how maltreated children
      deal with the experience. METHODS: Quantitative data were collected from face-to
      face interviews with 357 children aged between 9 and 12, living in protective
      care as a result of maltreatment. Among these children, qualitative data were
      collected from 14 children who experienced serious maltreatment using in-depth
      interviews. RESULTS: The results showed that, to a large extent, physical abuse
      very often occurred alongside emotional abuse. Most offenders were biological
      parents, who tended to be poor and have problems with alcohol. The majority of
      children in protective care were preschoolers. While in care, 40% of the children
      did not have any contact with their family for over a year. The results of the
      qualitative analysis of this study demonstrated that the abuse had multiple and
      long-term effects. CONCLUSIONS: This study confirms that many children living in
      Child Protective Services (CPS) have been abandoned by their families; moreover,
      they tend to lead highly unstable lives characterized by a vicious circle of
      being referred to protective care, returning to their families, experiencing a
      second round of abuse, then being readmitted to care. PRACTICAL IMPLICATIONS:
      This study emphasizes the need for communities to provide safe social support
      networks that can assist children who are victims of maltreatment to recover and
      readjust positively. It further suggests the need for a comprehensive holistic
      approach which takes the best interest of the child into primary consideration.

PMID- 20053453
TI  - Methodological challenges in measuring child maltreatment.
AB  - OBJECTIVE: This article reviewed the different surveillance systems used to
      monitor the extent of reported child maltreatment in North America. METHODS: Key
      measurement and definitional differences between the surveillance systems are
      detailed and their potential impact on the measurement of the rate of
      victimization. The infrastructure requirements, quality of information, timely
      access to data and the usefulness for child welfare policy are compared and
      contrasted and a summary table of the type of information by each system is
      presented. RESULTS: Two studies collect data regarding the extent and nature of
      child maltreatment using survey methodology reported to professionals: the United
      States National Incidence Study of Child Abuse and Neglect (NIS) and the Canadian
      Incidence Study of Reported Child Abuse and Neglect (CIS), and the United States
      National Child Abuse and Neglect Data System (NCANDS) uses administrative data
      methods to collect annual case-level and state data. PRACTICE IMPLICATIONS: The
      purpose of this comparison is to assist researchers and policy analysts with
      interpreting data from these studies as well as to help officials from other
      countries in developing surveillance systems that are appropriately adapted to
      their needs.

PMID- 20053454
TI  - Twenty years of the Convention on the Rights of the Child: achievements in and
      challenges for child protection implementation, measurement and evaluation around
      the world.

PMID- 20053456
TI  - WITHDRAWN: Health effects from long-range transported contaminants in Arctic top
      predators: An integrated review based on studies of polar bears and relevant
      model species.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.envint.2010.03.002. The
      duplicate article has therefore been withdrawn.

PMID- 20053455
TI  - Study of metals transfer from environment using teeth as biomonitor.
AB  - We investigated chronic incorporation of metals in individuals from poor
      families, living in a small, restrict and allegedly contaminated area in Sao
      Paulo city, the surroundings of the Guarapiranga dam, responsible for water
      supply to 25% of the city population. A total of 59 teeth from individuals 7 to
      60 years old were collected. The average concentrations of Pb, Cd, Fe, Zn, Mn, Ni
      and Cr were determined with an Atomic Absorption Spectrophotometer. The
      concentrations of all metals as function of the individuals' age exhibited a
      remarkable similarity: peaks between 7 and 10 years and sharply decreasing at
      higher ages, which could be attributed to alimentary habits and persistence to
      metals exposure all along the individuals' life span. From all the measured
      metals, lead and cadmium were a matter of much more concern since their measured
      values are close to the upper limits of the world wide averages.

PMID- 20053457
TI  - Cognition in elderly patients receiving unilateral and bilateral
      electroconvulsive therapy: a prospective, naturalistic comparison.
AB  - BACKGROUND: The cognitive side-effects of ECT are minimized by individualized,
      supra-threshold dosing with brief pulse electrical stimuli. Unilateral ECT is
      associated with fewer cognitive sequelae but bilateral ECT is possibly more
      effective. Little is known of the relative effectiveness and tolerability of the
      two placements in the treatment of elderly, severely depressed inpatients.
      METHODS: Patients of five public aged psychiatry services and a private
      psychiatric hospital who received right unilateral ECT (n=47) dosed on average at
      3 times seizure threshold or bitemporal ECT (n=16) dosed at 1.5 times threshold
      completed an abbreviated Rey Auditory Verbal Learning Test, a visual memory test
      and a section of the Autobiographical Memory Inventory as close as possible to
      24h after the first or second treatment and again after the fifth or sixth
      treatment. This design was intended to maximize recruitment of severely depressed
      patients with a limited ability to consent and cooperate with testing. RESULTS:
      Only 35% of eligible patients completed both assessments, mostly due to refusal
      or lack of capacity to consent. Moderate dose unilateral and bilateral ECT
      produced equivalent improvements in mood. There was a tendency for scores on most
      cognitive tests to decline more with bilateral than unilateral ECT but these
      differences were statistically significant only for immediate verbal memory and
      autobiographical memory. CONCLUSIONS: Our findings suggest that bilateral ECT is
      no more effective as an antidepressant than moderately dosed unilateral ECT, at
      least on a short-term basis, and confers a slightly greater risk of cognitive
      impairment. This supports the rationale of prescribing unilateral ECT in the
      first instance in this vulnerable clinical population. LIMITATIONS: It proved
      impossible to recruit most ECT recipients, limiting the capacity to generalize
      findings to all aged patients. Reports concerning ECT should list recruitment
      rates to help set findings in context.

PMID- 20053458
TI  - Factor structure of the Brief Psychiatric Rating Scale in unipolar depression.
AB  - BACKGROUND: In clinical practice patients with unipolar depression present with a
      variety of symptom clusters that may combine together in many different ways.
      However, only few factor analytic studies used general psychopathology scales to
      investigate the symptom structure of unipolar depression. METHODS: The study
      included 163 consecutive inpatients with an ICD-10 diagnosis of depressive
      disorder (ICD-10 codes F32 to F33). All patients were assessed with the 18-item
      version of the Brief Psychiatric Rating Scale (BPRS) within 3days from admission.
      Exploratory factor analysis with Varimax rotation was performed on BPRS items.
      RESULTS: Four factors were extracted, explaining 52% of total variance. They were
      interpreted as Apathy, Dysphoria, Depression and Psychoticism. The distribution
      of factor scores was approximately normal for Apathy, while it displayed a slight
      negative skewness for Depression, a slight positive skewness for Dysphoria, and a
      marked positive skewness for Psychoticism. Patient sex, family history of
      depression, lifetime history of suicide attempt, and recent serious family
      conflict were not associated with any factor. Occupational status, age, and age
      at onset displayed a positive correlation with Apathy. Duration of illness and
      number of previous admissions were positively correlated with Dysphoria.
      LIMITATIONS: Patients were not administered a structured diagnostic interview,
      and no detailed assessment of personality disorders was performed; also, patients
      were recruited only at a single site, which reduces the generalizability of the
      results. CONCLUSIONS: Our findings suggest that in depressive disorders there are
      psychopathological dimensions other than depressed mood that are worthy of
      greater clinical attention and research. Dimensions such as apathy and dysphoria
      may play an important part in the clinical phenomenology of unipolar depression
      and deserve systematic and careful assessment in order to provide patients with
      the best possible treatment and improve clinical outcomes.

PMID- 20053459
TI  - Interaction of catechol-O-methyltransferase (COMT) Val108/158 Met genotype and
      risperidone treatment in Chinese Han patients with schizophrenia.

PMID- 20053460
TI  - Expression profiling reveals differences in immuno-inflammatory gene expression
      between the two disease forms of sheep paratuberculosis.
AB  - Paratuberculosis is a chronic enteropathy of ruminants caused by Mycobacterium
      avium subspecies paratuberculosis (MAP); infection of sheep results in two
      disease forms - paucibacillary (tuberculoid) and multibacillary (lepromatous)
      associated with the differential polarization of the immune response. In addition
      the majority of MAP-infected animals show no pathology and remain asymptomatic.
      Microarray and real-time RT-qPCR analyses were used to compare gene expression in
      ileum from sheep with the two disease forms and asymptomatic sheep, to further
      understand the molecular basis of the pathologies. Microarrays identified 36
      genes with fold-change of >1.5 and P< or = 0.05 in at least one comparison; eight
      candidates were chosen for RT-qPCR validation. Sequence analysis of two
      candidates, CXCR4 and IGFBP6, identified three SNPs in each; five were found in
      all three forms of disease and showed no significant relationship to pathological
      type. The IGFBP6 G(3743) A SNP was not detected in asymptomatic sheep. The data
      show that the two forms of disease are associated with distinct molecular
      profiles highlighted by the differential expression of chemokine and chemokine
      receptor transcripts, the protein products of which might be implicated in the
      different cell infiltrates of the pathologies. The cells within the lesions also
      show evidence of abnormal activation; they express high levels of cytokine
      transcripts but have reduced expression levels of transcripts for T cell receptor
      associated molecules.

PMID- 20053461
TI  - Immunogenicity of recombinant GP5 protein of porcine reproductive and respiratory
      syndrome virus expressed in tobacco plant.
AB  - The aim of the study was to evaluate the immunogenicity of the ORF5-encoded major
      envelop glycoprotein 5 (GP5) of porcine reproductive and respiratory syndrome
      virus (PRRSV) expressed in tobacco plant as a potential pig oral vaccine in
      protection against PRRSV infection. Six-week-old PRRSV-free pigs were fed four
      times orally with 50g of chopped fresh GP5 transgenic tobacco leaves (GP5-T) (GP5
      reaching 0.011% of total soluble protein) or wild-type tobacco leaves (W-T) each
      on days 0, 14, 28, and 42. Samples of serum, saliva, and peripheral blood
      mononuclear cells (PBMCs) were collected on days -1, 6, 13, 20, 27, 34, 41, and
      48 after the initial oral vaccination. A similar vaccination-dependent gradual
      increase in the responses of serum and saliva anti-PRRSV total IgG and IgA,
      respectively, and in the levels of PRRSV-specific blastogenic response of PBMCs
      was seen in GP5-T-treated pigs; all statistically significant elevations occurred
      after the 2nd vaccination and were revealed after 20 days post-initial oral
      vaccination (DPIOV). Pigs fed on GP5-T also developed serum neutralizing
      antibodies to PRRSV at a titer of 1:4-1:8 after the 4th vaccination by 48 DPIOV.
      No detectable anti-PRRSV antibody responses and PRRSV-specific blastogenic
      response were seen in W-T-treated pigs. The present study has demonstrated that
      pigs fed on GP5-T could develop specific mucosal as well as systemic humoral and
      cellular immune responses against PRRSV. The results also support that transgenic
      plant as GP5-T can be an effective system for oral delivery of recombinant
      subunit vaccines in pigs.

PMID- 20053462
TI  - Intraspecific competition delays recovery of population structure.
AB  - Ecotoxicological field studies have shown that total abundance and biomass often
      recover shortly after pulsed toxicant stress. In contrast, population structure
      showed comparatively long-term alterations before reaching pre-treatment
      conditions. We investigated two mechanisms that may explain the prolonged
      recovery of population structure: latent toxicant effects on life-history traits
      on the individual level and competition on the population level. To test these
      hypotheses we exposed populations of Daphnia magna to a pulse of the pyrethroid
      Fenvalerate. For several generations the populations were kept at two different
      degrees of competition: strong competition at carrying capacity and reduced
      competition maintained by simulated predation. After disturbance due to
      Fenvalerate exposure, biomass recovered after 14-17 days. In contrast, size
      structure characterised by a lack of large and dominance of small organisms
      recovered after 43 days in populations with strong competition. Size structure
      recovered twice faster in populations with reduced competition. We explain this
      as follows: due to toxicant induced mortality, food availability and consequently
      birth rate increased and populations were dominated by small individuals. In
      populations without predation, these cohorts grew and eventually exerted high
      intraspecific competition that (i) stopped further growth of juveniles and (ii)
      increased mortality of adults. These demographic processes were mainly
      responsible for the prolonged recovery of size structure. In contrast, for
      populations with predation, the regular harvest of individuals reduced
      competition. Juveniles developed continuously, allowing a fast recovery of size
      structure in these dynamic populations. In risk assessment the duration for
      populations to recover from (toxicant) stress, is crucial for the determination
      of ecological acceptable effects. We conclude that competition needs to be
      considered in order to understand and predict recovery of size structure.

PMID- 20053463
TI  - Highly active human pharmaceuticals in aquatic systems: A concept for their
      identification based on their mode of action.
AB  - Widespread occurrence of traces of pharmaceuticals (ng/L to microg/L) has been
      reported in aquatic systems. However, their effects on the environment and their
      environmental risks remain elusive. Generally, the acute toxicity towards non
      target organisms has been assessed in laboratory experiments, but chronic
      toxicity studies have been performed only rarely. The guideline issued by the
      European Medicines Agency in 2006 is aimed at estimating the potential
      environmental risks of human pharmaceuticals by a tiered approach. The predicted
      environmental concentration (PEC) of a compound is estimated in phase I, and
      pharmaceuticals having a PEC above or equal 10ng/L undergo phase II testing.
      Otherwise they are not expected to pose a risk to the environment. Because some
      highly active compounds (HC) such as 17-alpha-ethinylestradiol, equine estrogens,
      trenbolone and the progestin levonorgestrel display adverse effects at
      concentrations below 10ng/L the question arises, whether additional HC compounds
      exist, and how they can be identified for undergoing environmental risk
      assessment. We addressed this question by searching for HC in the literature, and
      by developing a concept for identification of HC. The suggested mode of action
      concept is based on (i) the mode of action of the pharmaceutical taking the
      available toxicological information into account, (ii) the degree of sequence
      homology between the human drug target and the potential target in aquatic
      organisms and (iii) the importance of pathways affected by the pharmaceutical. We
      evaluated the mode of action concept by comparison to existing approaches, the
      fish plasma model (Huggett et al., 2003) and a QSAR model, called VirtualTox Lab
      (www.biograf.ch). All concepts result in similar classifications of the selected
      pharmaceuticals. However, there are some differences not only in the model
      assumptions, but also in its results. Our study leads to the conclusion that the
      mode of action concept is most suitable for the identification of HC. A
      refinement can be achieved by complementing this concept by the QSAR model
      (VirtualTox Lab), whereas the fish plasma model seemed to be less suitable due to
      the necessity of environmental concentration above 10ng/L for the identification
      of a risk.

PMID- 20053464
TI  - Selenate bioaccumulation and toxicity in Chlamydomonas reinhardtii: Influence of
      ambient sulphate ion concentration.
AB  - The aim of the present study was to investigate selenate toxicity in the
      unicellular green algae Chlamydomonas reinhardtii as a function of sulphate ion
      concentration and the relationship with intracellular bioaccumulation. The
      toxicity of selenate was evaluated by measuring the effect of different selenate
      concentrations on algal growth during a 96h exposure period. A non-linear
      regression according to the Hill model was used to describe the dose-effect
      relationship and estimate the effect concentrations (EC) of selenate. EC(50)
      values of 0.40[0.24-0.52]micromolL(-1) and of 3.10[1.65-4.86]micromolL(-1) of
      ambient selenate were obtained, at 8 and 80micromolL(-1) of sulphate ions in the
      medium, respectively. For non-toxic and low-level ambient selenate
      concentrations, bioaccumulation in presence of 80micromolL(-1) was one tenth that
      of 8micromolL(-1) of sulphate ions. When expressed as intracellular selenium
      burden, EC(50) values determined at 8 and 80micromolL(-1) of sulphate ions were
      not significantly different (126 and 67nmolSe.10(9)cells(-1), respectively). In
      conclusion, toxicity appeared to be correlated to selenate bioaccumulation which
      suggests that toxicity must be linked to intracellular selenium accumulation that
      is directly dependent on ambient sulphate ions that may compete with selenate for
      transport sites.

PMID- 20053465
TI  - Flow cytometric analysis of BDE 47 mediated injury to rainbow trout gill
      epithelial cells.
AB  - The polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental
      contaminants whose residues are increasing in fish, wildlife and human tissues.
      However, relatively little is known regarding the mechanisms of cell injury
      caused by PBDE congeners in fish. In the present study, we employed flow
      cytometry-based analyses to understand the onset and mechanisms of cell injury in
      rainbow trout gill cells (RTgill-W1 cells) exposed to 2,2',4,4'
      tetrabromodiphenyl ether (BDE 47). Substantial optimization and validation for
      flow cytometry protocols were required during assay development for the trout
      gill cell line. Exposure to micromolar concentrations of BDE 47 elicited a
      significant loss in RTgill-W1 cell viability that was accompanied by a decrease
      in NAD(P)H autofluorescence, a marker associated with disruption of cellular
      redox status. This loss in NAD(P)H content was accompanied by a decrease in nonyl
      acridine orange fluorescence, indicating mitochondrial membrane lipid
      peroxidation. Furthermore, low doses of BDE 47 altered cellular forward angle
      light scatter (FS, a measure of cell diameter or size) and side light scatter
      properties (SS, a measure of cellular internal complexity), consistent with the
      early stages of apoptosis. These changes were more pronounced at higher BDE 47
      concentrations, which led to an increase in the percentage of cells undergoing
      frank apoptosis as evidenced by sub-G1 DNA content. Apoptosis was also observed
      at a relatively low dose (3.2muM) of BDE 47 if cells were exposed for an extended
      period of time (24h). Collectively, the results of these studies indicate that
      exposure of rainbow trout gill cells to BDE47 is associated with the induction of
      apoptosis likely originating from disruption of cellular redox status and
      mitochondrial oxidative injury. The current report extends observations in other
      species demonstrating that oxidative stress is an important mechanism of BDE 47
      mediated cellular toxicity, and supports the use of oxidative stress-associated
      biomarkers in assessing the sublethal effects of PBDEs and their replacements in
      fish. The application of flow cytometry endpoints using fish cell lines should
      facilitate study of the mechanisms of chemical injury in aquatic species.

PMID- 20053467
TI  - Left bundle branch block and changing axis deviation during acute myocardial
      infarction.
AB  - Changing axis deviation has been reported also during atrial fibrillation or
      atrial flutter. Changing axis deviation has been also reported during acute
      myocardial infarction associated with atrial fibrillation too or at the end of
      atrial fibrillation during acute myocardial infarction. Left bundle branch block
      is usually associated with normal or left axis deviation. Rarely the ECG shows a
      left bundle branch block with changing QRS morphology and changing axis
      deviation. We present a case of a left bundle branch block with changing axis
      deviation in an 86-year-old Italian man admitted to the Cardiology Unit with an
      acute myocardial infarction. Also this case focuses attention on left bundle
      branch block with changing axis deviation.

PMID- 20053466
TI  - Opposing cardiac effects of autoantibody activation of beta-adrenergic and M2
      muscarinic receptors in cardiac-related diseases.
AB  - BACKGROUND: Activating autoantibodies to beta-adrenergic receptors (AAbeta1/2AR)
      and M2 muscarinic receptors (AAM2R) have been reported in several cardiac
      diseases and may have pathophysiologic relevance. However, the interactions and
      relative effects of AAbeta1AR, AAbeta2AR and AAM2R on contractile function have
      not been characterized. METHODS: The inotropic effects of IgG from 18 selected
      patients with cardiomyopathy and/or atrial tachyarrhythmias positive by ELISA for
      antibodies to beta1/2AR were studied using an isolated canine Purkinje fiber
      contractility assay. M2R-blockade was tested using atropine while selective
      beta1AR and beta2AR blockade used CGP-20712A and ICI-118551 respectively.
      RESULTS: Fifteen of the 18 anti-beta1/2AR ELISA-positive samples demonstrated
      evidence for negative inotropic muscarinic effects which were blocked using
      atropine. Atropine failed to uncover a positive inotropic response in 2 of the 18
      IgG samples (false positive ELISA for AAbetaAR). In the remaining 16 AAbetaAR
      true-positive subjects, the beta1AR-induced increase in contractility (concurrent
      M2/beta2 blockade) was augmented to 140.5+/-12.2% of baseline compared to 127.4+/
      7.2% of baseline with M2 blockade (atropine) only (p<0.001, n=16). The beta2AR
      induced increase in contractility (concurrent M2/beta1 blockade) was only 114.5+/
      4.3% of baseline (p<0.001, n=16). Combined M2 and beta1/beta2 blockade eliminated
      any increase in contractility. CONCLUSIONS: The inherently positive inotropic
      effect of AAbeta1AR was negatively modulated by AAM2R and AAbeta2AR. These
      opposing effects of receptor-activating autoantibodies may alter cardiac
      performance and influence clinical outcome depending on their receptor type and
      relative contractile activity.

PMID- 20053469
TI  - Simultaneous estimation of NT-proBNP on top to mitral flow Doppler
      echocardiography as an accurate strategy to diagnose diastolic dysfunction in
      HFNEF.
AB  - BACKGROUND: Conventional echocardiography has limited accuracy in detecting
      diastolic dysfunction and NT-proBNP is known to be a reliable biomarker to rule
      out heart failure. Therefore NT-proBNP on top to conventional mitral flow Doppler
      might improve the diagnostic of diastolic dysfunction in patients with heart
      failure despite normal EF (HFNEF) without using tissue Doppler. METHODS AND
      RESULTS: Diastolic function of 46 patients with HFNEF was determined by pressure
      volume loop obtained by conductance-catheter measurements. LV stiffness
      correlated with the amount of collagen types I and III analyzed from
      endomyocardial biopsies (EMBs). NT-proBNP plasma levels correlated with LV
      stiffness, LVEDP and the collagen amount from EMBs (p<0.01). In another set of
      patients with HFNEF (n=107, 53 [45-62] years), diastolic dysfunction was
      confirmed by left and/or right heart catheterization. Their Doppler indices and
      plasma marker NT-proBNP values were compared with those of 73 controls (186 [70
      342] vs 54[30-75] pg/ml, p<0.001). Mitral flow Doppler was impaired in 70/107
      (65%) of the HFNEF. When additional criterium NT-proBNP>125 pg/ml was used 96/107
      (90%) patients with impaired diastolic function were recognized. Sensitivity of
      tissue Doppler indices E'/A' and E/E' were improved by 4-6% using NT-proBNP on
      top. NT-proBNP recognized HFNEF patients with higher hospitalization rate
      indicated by phone questionnaire, whereas Doppler indices alone did not.
      CONCLUSION: Plasma NT-proBNP levels are associated with increased LV stiffness
      and cardiac collagen content. On top measurements of plasma NT-proBNP improve the
      echocardiography diagnostic of diastolic function and prognostic of
      rehospitalization in HFNEF.

PMID- 20053468
TI  - Blockade of TGF-beta by catheter-based local intravascular gene delivery does not
      alter the in-stent neointimal response, but enhances inflammation in pig coronary
      arteries.
AB  - BACKGROUND: Extracellular matrix (ECM) accumulation significantly contributes to
      in-stent restenosis. In this regard, transforming growth factor (TGF)-beta, a
      positive regulator of ECM deposition, may be implicated in in-stent restenosis.
      The goal of this study was to assess the effect of blockade of TGF-beta on stent
      induced restenosis in porcine coronary arteries. METHODS: An adenovirus
      expressing the ectodomain of the TGF-beta type II receptor (AdTbeta-ExR) was
      applied onto a coronary arterial segment of a pig (n=10) using an Infiltrator,
      followed by stent deployment. Controls consisted of adenoviruses expressing beta
      galactosidase (AdLacZ) or phosphate-buffered saline (PBS) applied onto the other
      segment (n=10) of the same pig. RESULTS: Computer-based pathological morphometric
      analysis of stented coronary arteries, performed 4 weeks after stenting,
      demonstrated no significant difference in morphometric parameters such as in
      stent neointimal area and % area stenosis between the AdTbeta-ExR group and
      control (n=7 for each). However the AdTbeta-ExR group had increased neointimal
      cell density, infiltration of inflammatory cells mostly consisting of CD3+ T
      cell, accumulation of hyaluronan, cell proliferation rate, and adventitial matrix
      metalloproteinase-1 (MMP-1) expression compared with control. The expression of
      connective tissue growth factor mRNA, measured by reverse transcription PCR, in
      cultured rat arterial smooth muscle cells was inhibited by AdTbeta-ExR at moi 60.
      CONCLUSIONS: Blockade of TGF-beta by catheter-based local intravascular gene
      delivery does not reduce stent-induced neointima formation 4 weeks after stenting
      in spite of modest inhibition of ECM accumulation, but it induces vascular
      inflammation and associated pathological changes that may potentially aggravate
      lesion progression.

PMID- 20053470
TI  - A multicenter study of the association of serum uric acid, serum creatinine, and
      diuretic use in hypertensive patients.
AB  - BACKGROUND: Individuals with hypertension and hyperuricemia have an increased
      risk of coronary artery disease and cerebral vascular disease as compared to
      patients with normal uric acid levels. Our aim is to determine the prevalence of
      hyperuricemia in hypertensive patients in Taiwan, and whether serum uric acid
      (SUA) is associated with changes in renal function in patients with hypertension.
      METHODS: We studied 2145 hypertensive patients receiving medical treatment,
      assessed the prevalence of hyperuricemia, and determined the independent risk
      factors for SUA. Simple correlation and multiple regression analyses were applied
      to identify the independent risk factors for SUA increase. Logistic regression
      analysis was used to estimate the association between 4 quartiles of SUA level
      and correspondent serum creatinine (SCr) concentrations. RESULTS: Hypertensive
      subjects had a high prevalence of hyperuricemia (men, 35%; women, 43%). SUA was
      significantly associated with the independent risk factors of SCr, diuretic
      usage, and diabetes (inversely related) in both genders, whereas beta-blocker
      usage and body mass index were only associated in men. Multiple logistic
      regression models showed that in the non-diuretic user group the highest SUA
      quartile entailed >4 times greater risk for SCr elevation than the lowest. In the
      diuretic user group, a >2 times greater risk was noted. CONCLUSIONS:
      Hyperuricemia hypertensive subjects demonstrated a corresponding elevation of SUA
      and SCr irrespective of diuretic use. Elevation of SUA, in addition to SCr, may
      represent a progression of renal function impairment.

PMID- 20053471
TI  - Differential levels of circulating progenitor cells in acute coronary syndrome
      patients with a first event versus patients with recurring events.
AB  - OBJECTIVE: Pathophysiology of acute coronary syndromes in patients presenting
      with a first cardiac event (FCE) can be different from patients with a recurring
      cardiac event (RCE). We assessed inflammatory activation and circulating
      progenitor cells' (CPC) mobilisation in patients with a FCE versus those with
      RCE. METHODS: We recruited 41 patients: 18 with FCE and 23 with RCE. Peripheral
      blood samples were drawn at baseline and at 20 days to measure high sensitivity C
      reactive protein (CRP) and to assess CD34+/133+ CPC and CD34+/KDR+ CPC by flow
      cytometry. RESULTS: CD34+/133+ cells (% number of cells per total number of
      cytometric events) were similar at baseline, being 0.25% (0.17-0.42%) in the FCE
      vs 0.23% (0.11-0.43%) in the RCE group, and increased at follow-up only in the
      FCE group to 0.41% (0.22-0.64%), while in the RCE group they were 0.27% (0.11
      0.36%) (p=0.009 for the interaction, p=0.07 for the main effect of time).
      CD34+/KDR+ cells were similar at baseline in the two groups, did not
      significantly increase over time (p=0.2), and no differential effect of FCE vs
      RCE over time was seen (p=0.38). CRP levels, similar at baseline, were
      consistently reduced at 20 days after ACS (p=0.001), with no differential effect
      of FCE vs RCE pts (p=0.74). Variation from baseline to follow-up for both
      CD34+/133+ and CD34+/KDR+ did not correlate with either baseline CRP or delta
      CRP. CONCLUSIONS: Our data demonstrate a differential CPC mobilization behavior
      for FCE patients compared to RCE ones, independent of inflammatory activation.

PMID- 20053472
TI  - Intravascular optical coherence tomography (OCT) during contrast injection: a
      leap forward in intracoronary imaging.
AB  - Imaging the coronary vasculature using Optical Coherence Tomography (OCT) is now
      possible using motorised pullback during contrast injection.

PMID- 20053473
TI  - Demonstrating freedom from Mycobacterium bovis infection in Swedish farmed deer
      using non-survey data sources.
AB  - Sweden has been considered free from bovine tuberculosis (BTB) since 1958. In
      1987 an infected consignment of farmed deer was imported to Sweden and in 1991
      the first infected deer was identified. Despite a thorough trace back
      investigation, all deer originating from the infected consignment could not be
      traced. Therefore a national control programme for BTB in farmed deer was
      implemented. At present the control programme is in its final stage and all deer
      holdings that have not obtained BTB-free status are put under restrictions. This
      study aimed to determine the probability that the Swedish farmed deer population
      is free from BTB using methods that allow analysis of non-structured data, i.e.
      results from meat inspection, necropsies and tuberculin testing. Surveillance
      data from 1994 to October 2006 from farmed deer affiliated to the voluntary
      control programme were analysed using the model described in Martin et al.
      (2007a). The model was adjusted to allow the within-herd design prevalence to be
      defined as one infected deer per herd and the between-herd design prevalence to
      be defined as one infected deer herd in the country. Depending on the chosen
      within-herd design prevalence: 1, 2, 3 or 4 infected deer per herd or 5% infected
      deer per herd, the probability of freedom from BTB infection in the Swedish
      farmed deer population varied between 87% and 97%. Based on the obtained results,
      it can be concluded, with high confidence, that the Swedish farmed deer
      population is free from M. bovis.

PMID- 20053474
TI  - Retail price regulation and innovation: reference pricing in the pharmaceutical
      industry.
AB  - Our paper is a first attempt to evaluate the long run impact of reference pricing
      on pharmaceutical innovation, health and expenditures. The model is based on a
      dynamic game involving three types of agents: pharmaceutical firms, consumers and
      a regulatory entity. Pharmaceutical firms choose the level of research investment
      and its innovative content, then negotiate introductory prices for new drugs with
      the regulator. Reference pricing affects negatively the intensity of research and
      it also modifies the types of innovations that are brought to the market,
      deterring small innovations. The model is calibrated with a small data on statins
      in France. Our results suggest that reference pricing typically generates a
      decline in health, whereas discounted expenditures may decrease or increase,
      depending on the degree of deterrence of cost reducing innovations.

PMID- 20053475
TI  - Genetic association of the neuropilin-1 gene with type 1 diabetes in children:
      Neuropilin-1 expression in pancreatic islets.
AB  - Minor alleles of two SNPs in intron 9 of the NRP1 gene, which encodes neuropilin
      1, were found to be associated with type 1 diabetes (T1D) in children. Neuropilin
      1 peptides were confined to islets in human pancreas. This suggests neuropilins-1
      could influence the development of some cases of T1D in children.

PMID- 20053476
TI  - Second-line weekly paclitaxel in resistant or relapsed non-small cell lung cancer
      treated with docetaxel and carboplatin: a multi-center phase II study.
AB  - We conducted a phase II trial to evaluate the safety and efficacy of weekly
      paclitaxel in patients with resistant or relapsed non-small cell lung cancer
      (NSCLC) treated with docetaxel and carboplatin. Thirty-two NSCLC patients at a
      median age of 58.0 years (range 33-75) were enrolled. The Eastern Cooperative
      Oncology Group performance status scores (0/1/2) were 18/9/5, respectively. The
      majority of patients had adenocarcinoma (84%) and stage IV disease (81%). The
      response rate for the first-line chemotherapy was 28%. Paclitaxel was
      administered at a dose of 80 mg/m(2) as an intravenous infusion 60 min weekly for
      6 consecutive weeks of an 8-week cycle. All patients were assessable for response
      and toxicity. The median number of cycles administered was two (range 1-8), and
      the overall response rate was 15.6%. The median survival time (MST) was 10.6
      months (95% CI=8.2-12.5), while the 1-year survival rate was 37.5%, and the
      median progression-free survival was 4.9 months (95% CI=3.0-7.1). Hematological
      toxicities (grade 3 or 4) were observed in 15 patients (46.9%) with leukopenia,
      and in 4 (12.5%) with anemia. Non-hematological toxicity was generally mild,
      though grade 3 anorexia was observed in 3 patients (9.3%). No treatment-related
      deaths were observed. In conclusion, second-line weekly paclitaxel is effective
      in NSCLC patients treated with docetaxel plus carboplatin and is associated with
      a tolerable toxicity profile.

PMID- 20053477
TI  - [Architectural analysis of clear corneal incisions using Visante OCT in acute
      postoperative endophthalmitis].
AB  - PURPOSE: To analyze the architecture of clear corneal incisions after acute
      endophthalmitis following cataract surgery using anterior segment OCT (AS-OCT).
      PATIENTS AND METHODS: Fourteen eyes of 14 patients followed at the Quinze-Vingts
      National Ophthalmology Hospital for acute endophthalmitis following cataract
      surgery, between April and November 2008, were included in this study. All
      patients had a complete biomicroscopic examination and a Visante-OCT (Carl Zeiss
      Meditec AG) analysis of the corneal incision. The length, size (width), location,
      angle, architecture, and anatomic imperfections of the incisions were analyzed.
      RESULTS: Symptoms occurred 4+/-2.4 days after cataract surgery. The location of
      the incision was superior in 71.43% of cases, temporal in 21.43% and nasal in
      7.14%. Incision size (width) was 3.2 mm in 42.86% of cases, 2.75 mm in 35.71%,
      and 3 mm in 21.43%. Two incisions were sutured (14.28%). Using AS-OCT, the mean
      incision length was 1.42+/-0.25 mm and the mean incision angle was 39+/-10.62
      degrees . Three-step incisions were found in 35.71% of cases and endothelial
      gaping was found in 42.86 % of cases. CONCLUSION: A reduced incision length and
      inappropriate construction seemed to be determinant risk factors of
      endophthalmitis following cataract surgery. Other studies using a greater number
      of patients with an architectural analysis of clear corneal incisions are
      necessary to confirm these preliminary results.

PMID- 20053479
TI  - [Indication of determination of antibodies against hepatitis C and A viruses in
      the protocol for the care of young immigrants].
AB  - OBJECTIVES: To evaluate systematic determination of antibodies against hepatitis
      C virus (HCV) and hepatitis A virus (HAV) within the protocols for the care of
      young immigrants (PCYI). METHODS: We performed a descriptive, cross-sectional,
      multicenter study. Antibodies against HCV and HAV were determined in children
      aged from 6 months to 15 years from low-income countries who had immigrated to
      Spain less than 12 months previously. Age, sex and country of origin were
      registered. The cost of vaccinating all immigrant children (with the HA vaccine
      and HA-HB vaccine, public health price and retail price) without screening was
      compared with that of vaccinating non-immune children only. RESULTS: HCV
      antibodies were determined in 1055 children and only one was positive [0.09% (95%
      CI: 0-0.53%)]. HAV antibodies were determined in 992 children and, overall, 38%
      were positive (95% CI: 35.0-41.1). Distribution by country of origin was as
      follows: Central and South America (n=352) 34.9%, Maghreb (n=246) 44.7%, and
      India, Pakistan and Bangladesh (n=162) 58.6%. According to the children's age,
      country of origin, and the price of the vaccine used, HAV antibody determination
      in young immigrants before HAV vaccination is efficient. CONCLUSIONS: Because of
      the low prevalence of HCV antibodies in the pediatric immigrant population,
      systematic determination is not warranted. Evaluating HAV antibodies in each
      immigrant child could increase the efficiency of PCYI.

PMID- 20053480
TI  - Synthesis and antimicrobial activities of novel 1,5-diaryl pyrazoles.
AB  - Novel 1,5-diaryl pyrazole derivatives viz. 5-(4-chlorophenyl)-1-(4-fluorophenyl)
      1H-pyrazole-3-carboxamides (2a-e, 3, 3a-f), 2-(5-(4-chlorophenyl)-1-(4
      fluorophenyl)-1H-pyrazole-3-yl)thiazoles (6a-c,7, 8, 9a-c, 10, 11) were
      synthesized by varying the active part (amide group) of pyrazole, characterized
      using IR, (1)H NMR, mass spectral data and screened for their antibacterial
      activity against Escherichia coli (ATTC-25922), Staphylococcus aureus (ATTC
      25923), Pseudomonas aeruginosa (ATTC-27853), Klebsiella pneumonia. Similarly all
      these compounds were screened for their antifungal activity against Aspergillus
      flavus (NCIM No. 524), Aspergillus fumigates (NCIM No. 902), Penicillium
      marneffei and Trichophyton mentagrophytes. Interestingly all the synthesized
      compounds exhibited good antibacterial (except 2a-c, 8, 9a) and antifungal
      activity (except 2a-c, 6a, 8, 9a).

PMID- 20053478
TI  - 17beta-Estradiol regulates insulin-degrading enzyme expression via an ERbeta/PI3
      K pathway in hippocampus: relevance to Alzheimer's prevention.
AB  - Insulin-degrading enzyme (IDE), an enzyme that primarily degrades insulin, has
      recently been demonstrated to play a significant role in the catabolism of
      amyloid beta (Abeta) protein in the brain. Reduced IDE expression and/or activity
      have been associated with the etiology and development of Alzheimer's disease
      (AD). Using three model systems, the present investigation provides the first
      documentation indicating that estrogen robustly regulates the expression of IDE
      in normal, menopausal and early-stage AD brains. In vitro analyses in primary
      cultures of rat hippocampal neurons revealed that 17beta-estradiol (17beta-E2)
      increased IDE in both mRNA and protein levels in a time-dependent manner. Further
      pharmacological analyses indicated that 17beta-E2-induced IDE expression was
      dependent upon estrogen receptor (ER) beta and required activation of
      phosphatidylinositol 3-kinase (PI3-K). In vivo analyses in adult female rats
      revealed a brain region-specific responsive profile. Ovariectomy (OVX) induced a
      significant decline in IDE expression in the hippocampus, which was prevented by
      17beta-E2. Neither OVX nor 17beta-E2 affected IDE expression in the cerebellum.
      In vivo analyses in triple transgenic AD (3xTg-AD) female mice revealed an
      inverse correlation between the age-related increase in Abeta load and the
      decrease in IDE expression in the hippocampal formation. Treatment with 17beta-E2
      attenuated Abeta accumulation/plaque formation and elevated hippocampal IDE
      expression in 12-month-old 3xTg-AD OVX mice. Collectively, these findings
      indicate that 17beta-E2 regulates IDE expression in a brain region-specific
      manner and such a regulatory role in the hippocampus, mediated by an ERbeta/PI3-K
      pathway, could serve as a direct mechanism underlying estrogen-mediated
      preventative effect against AD when initiated at the onset of menopause.

PMID- 20053481
TI  - Synthesis, characterization and antibacterial activities of some new ferrocene
      containing penems.
AB  - The synthesis and structure-activity relationships of a series of new penems
      bearing ferrocenyl group attached to the C-2 position of the penem nucleus were
      described. The beta-lactanic derivatives obtained had been characterized as
      sodium salts, through (1)H NMR and IR, as well as through element analysis. Their
      in vitro antibacterial activities against both Gram-positive including meticillin
      resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria were tested.
      Most of the penems exhibited superior or equivalent efficacy of antibacterial
      activity as well as high stability to renal dehydropeptidase-I (DHP-I) compared
      with faropenem. In particular, the compound 14h having a heterocyclic group
      showed the most potent antibacterial activity.

PMID- 20053482
TI  - Hydrogenative desulphurization of thienopyrrolizinones: an easy and selective
      access to (Z)-phenethylidenepyrrolizinones with in vitro cytotoxic activity.
AB  - Attempts in view to dearomatize some previously reported tripentones with potent
      antineoplastic activities led in thiophene series to an unexpected hydrogenative
      desulphurization reaction. The resulting (Z)-phenethylidenepyrrolizinones were
      tested in vitro over human epidermoid carcinoma KB cell line. The results of this
      biological evaluation indicated that the tricyclic core of our model can be
      cleaved with a partial respect of the activity.

PMID- 20053483
TI  - Ruthenium(II)-arene complexes with functionalized pyridines: synthesis,
      characterization and cytotoxic activity.
AB  - Ruthenium(II)-arene complexes of general formulae [(eta(6)-p-cymene)Ru(L(1
      3))Cl(2)], where L(1-3) is 3-acetylpyridine (1), 4-acetylpyridine (2) and 2-amino
      5-chloropyridine (3), correspondingly, [(eta(6)-p-cymene)Ru(HL(4,5))Cl(2)], where
      HL(4) and HL(5) are respectively isonicotinic acid (4) and nicotinic acid (5) and
      [(eta(6)-p-cymene)Ru(HL(6-9))Cl], where H(2)L(6-9) represent 2,3
      pyridinedicarboxylic acid (6), 2,4-pyridinedicarboxylic acid (7), 2,5
      pyridinedicarboxylic acid (8) and 2,6-pyridinedicarboxylic acid (9), were
      prepared by the reaction of [(eta(6)-p-cymene)(2)RuCl(2)](2) (10) with the
      corresponding ligand in 1:2 molar ratio in isopropanol. The complexes were
      characterized by elemental analysis, mass spectrometry, IR and NMR
      spectroscopies. According to these data the molecules adopt the usual "three-leg
      piano-stool" geometry which is common for this type of complexes. The structures
      of 1 and 7 were determined by X-ray crystallography. The complexes revealed low
      antiproliferative activity in six investigated tumor cell lines (HeLa, B16, FemX,
      MDA-MB-361, MDA-MB-453 and LS-174). The reaction of 6 with 9-methyladenine was
      studied by (1)H NMR, (1)H, (1)H COSY and (1)H, (1)H NOESY spectroscopy.

PMID- 20053484
TI  - Prediction of acetylcholinesterase inhibitors and characterization of correlative
      molecular descriptors by machine learning methods.
AB  - Acetylcholinesterase (AChE) has become an important drug target and its
      inhibitors have proved useful in the symptomatic treatment of Alzheimer's
      disease. This work explores several machine learning methods (support vector
      machine (SVM), k-nearest neighbor (k-NN), and C4.5 decision tree (C4.5 DT)) for
      predicting AChE inhibitors (AChEIs). A feature selection method is used for
      improving prediction accuracy and selecting molecular descriptors responsible for
      distinguishing AChEIs and non-AChEIs. The prediction accuracies are 76.3%
      approximately 88.0% for AChEIs and 74.3% approximately 79.6% for non-AChEIs based
      on the three kinds of machine learning methods. This work suggests that machine
      learning methods such as SVM are facilitating for predicting AChEIs potential of
      unknown sets of compounds and for exhibiting the molecular descriptors associated
      with AChEIs.

PMID- 20053485
TI  - Synthesis of highly functionalized barbituric acids and study of their
      interactions with p-glycoprotein and Mg2+--potential candidates for multi drug
      resistance modulation.
AB  - A number of barbituric acids with appropriate substituent at C-5 position were
      synthesized and investigated for their interactions with p-gp and Mg(2+).
      Compounds 5, 6, 8-10, 12-14 and 16 increased the basal activity of p-gp by more
      than 50% at 0.05 muM concentration. Molecular docking indicate a number of H-bond
      interactions between these molecules and the amino acid residues of ATP binding
      site of p-gp. These molecules also showed appreciable interactions with Mg(2+),
      an important component of efflux pump. All the results of these investigations
      favor the suitability of barbituric acids toward MDR modulation.

PMID- 20053486
TI  - Predictive comparative QSAR modelling of (phenylpiperazinyl-alkyl) oxindoles as
      selective 5-HT1A antagonists by stepwise regression, PCRA, FA-MLR and PLS
      techniques.
AB  - 5-Hydroxytryptamine, a neurotransmitter released by 5-HT neurons in raphe nuclei
      and 5-HT(1A) receptors are involved in the pain mechanism of migraine, prevention
      of postpartum haemorrhage, CNS effects like sleep, anxiety and thermoregulation.
      Comparative QSAR study was done on thirtytwo (phenylpiperazinyl-alkyl) oxindoles
      using stepwise regression, PCRA, FA-MLR and PLS techniques to find structurally
      significant models. ETSA indices at atom numbers 19, 20 and 22, RTSA indices at
      atom numbers 6, 10 and 20, charge at atom number 19 and presence of chlorine at
      the atom number 6 may be conducive for the receptor inhibition. Electrophilic
      attack at atom number 21 may be unfavourable but nucleophilic attack at atom
      numbers 8 and 14 may be beneficial for % 5-HT(1A) inhibition.

PMID- 20053487
TI  - [Infectious adverse events related to misuse of high-dose buprenorphine: a
      retrospective study of 42 cases].
AB  - PURPOSE: Misuse of high-dose buprenorphine (HDB), mainly by injection, is
      responsible of frequent infectious adverse events. METHODS: This is a
      retrospective study of infectious complications occurring in patients using HDB
      by injection. Forty-two cases were identified (29 men and ten women) and the data
      were collected between March 1999 and December 2008. RESULTS: The infectious
      complications included cutaneous infections (27 cases), endocarditis (nine
      cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis),
      and a vascular embolism with decrease in visual acuity. CONCLUSION: The results
      of HDB maintenance treatment must be improved, both from the point of view of
      substitution and to limit its misuse by intravenous route injection. Health
      professionals have to play an important role in drug addict patients' education
      and supervision, to prevent buprenorphine injection and related infectious
      complications.

PMID- 20053488
TI  - A comparison of the psychometric properties of three- and four-option multiple
      choice questions in nursing assessments.
AB  - In multiple-choice tests, four-option items are the standard in nursing
      education. There are few evidence-based reasons, however, for MCQs to have four
      or more options as studies have shown that three-option items perform equally as
      well and the additional options most often do not improve test reliability and
      validity. The aim of this study was to examine and compare the psychometric
      properties of four-option items with the same items rewritten as three-option
      items. Using item-analysis data to eliminate the distractor with the lowest
      response rate, we compared three- and four-option versions of 41 multiple-choice
      items administered to two student cohorts over two subsequent academic years.
      Removing the non-functioning distractor resulted in minimal changes in item
      difficulty and discrimination. Three-option items contained more functioning
      distractors despite having fewer distractors overall. Existing distractors became
      more discriminating when infrequently selected distractors were removed from
      items. Overall, three-option items perform equally as well as four-option items.
      Since three-option items require less time to develop and administer and
      additional options provide no psychometric advantage, teachers are encouraged to
      adopt three-option items as the standard on multiple-choice tests.

PMID- 20053489
TI  - Development of a training curriculum for microsurgery.
AB  - Recent changes in healthcare necessitate revision of the current apprenticeship
      model of surgical training. Current methods of assessment such as examinations
      and logbooks are not criteria-based, so are subjective and lack validity and
      reliability. The objective feedback of technical skills is crucial to the
      structured learning of surgical skills. We review current publications about
      training and methods of assessment in microsurgery. Searches on PubMed using
      keywords (microsurgery, training, assessment, simulation, and skill) were used to
      retrieve relevant articles, and further cross-referencing was done to obtain more
      information. New methods of assessment that are objective include checklists,
      global rating scales (GRS), and dexterity analysis, which give feedback of
      technical skills during training. Vital (living), non-vital, prosthetic, and
      virtual reality simulation models can be used to train surgeons to a proficient
      level outside the operating theatre before they operate on real patients. After
      reviewing the current evidence we propose a curriculum for microsurgical training
      that starts outside the operating theatre. The surgical community should follow
      the example of other high-risk industries such as aviation, where continuous
      assessment on simulators is a part of training, but further research is necessary
      before such methods can be used for summative assessment and revalidation.

PMID- 20053490
TI  - Polyfluoroalkyl compounds in landfill leachates.
AB  - Polyfluoroalkyl compounds (PFCs) are widely used in industry and consumer
      products. These products could end up finally in landfills where their leachates
      are a potential source for PFCs into the aqueous environment. In this study,
      samples of untreated and treated leachate from 22 landfill sites in Germany were
      analysed for 43 PFCs. SigmaPFC concentrations ranged from 31 to 12,819 ng/L in
      untreated leachate and 4-8060 ng/L in treated leachate. The dominating compounds
      in untreated leachate were perfluorobutanoic acid (PFBA) (mean contribution 27%)
      and perfluorobutane sulfonate (PFBS) (24%). The discharge of PFCs into the
      aqueous environment depended on the cleaning treatment systems. Membrane
      treatments (reverse osmosis and nanofiltrations) and activated carbon released
      lower concentrations of PFCs into the environment than cleaning systems using wet
      air oxidation or only biological treatment. The mass flows of summation
      operatorPFCs into the aqueous environment ranged between 0.08 and 956 mg/day.

PMID- 20053491
TI  - Systems-level modeling the effects of arsenic exposure with sequential pulsed and
      fluctuating patterns for tilapia and freshwater clam.
AB  - The purpose of this paper was to use quantitative systems-level approach
      employing biotic ligand model based threshold damage model to examine
      physiological responses of tilapia and freshwater clam to sequential pulsed and
      fluctuating arsenic concentrations. We tested present model and triggering
      mechanisms by carrying out a series of modeling experiments where we used
      periodic pulses and sine-wave as featured exposures. Our results indicate that
      changes in the dominant frequencies and pulse timing can shift the safe rate
      distributions for tilapia, but not for that of freshwater clam. We found that
      tilapia increase bioenergetic costs to maintain the acclimation during pulsed and
      sine-wave exposures. Our ability to predict the consequences of physiological
      variation under time-varying exposure patterns has also implications for
      optimizing species growing, cultivation strategies, and risk assessment in
      realistic situations.

PMID- 20053492
TI  - Differential fate of erythromycin and beta-lactam resistance genes from swine
      lagoon waste under different aquatic conditions.
AB  - The attenuation and fate of erythromycin-resistance-methylase (erm) and extended
      spectrum beta-lactamse (bla) genes were quantified over time in aquatic systems
      by adding 20-L swine waste to 11,300-L outdoor mesocosms that simulated receiving
      water conditions below intensive agricultural operations. The units were prepared
      with two different light-exposure scenarios and included artificial substrates to
      assess gene movement into biofilms. Of eleven genes tested, only erm(B), erm(F),
      bla(SHV) and bla(TEM) were found in sufficient quantity for monitoring. The genes
      disappeared rapidly from the water column and first-order water-column
      disappearance coefficients were calculated. However, detected gene levels became
      elevated in the biofilms within 2 days, but then disappeared over time.
      Differences were observed between sunlight and dark treatments and among
      individual genes, suggesting that ecological and gene-specific factors play roles
      in the fate of these genes after release into the environment. Ultimately, this
      information will aid in generating better predictive models for gene fate.

PMID- 20053493
TI  - Field-scale leaching of arsenic, chromium and copper from weathered treated wood.
AB  - Earlier studies documented the loss of wood preservatives from new wood. The
      objective of this study was to evaluate losses from weathered treated wood under
      field conditions by collecting rainfall leachate from 5 different wood types, all
      with a surface area of 0.21 m(2). Wood samples included weathered chromate copper
      arsenate (CCA) treated wood at low (2.7 kg/m(3)), medium (4.8 kg/m(3)) and high
      (35.4 kg/m(3)) retention levels, new alkaline copper quat (ACQ) treated wood (1.1
      kg/m(3) as CuO) and new untreated wood. Arsenic was found to leach at a higher
      rate (100 mg in 1 year for low retention) than chromium and copper (<40 mg) in
      all CCA-treated wood samples. Copper leached at the highest rate from the ACQ
      sample (670 mg). Overall results suggest that metals' leaching is a continuous
      process driven by rainfall, and that the mechanism of release from the wood
      matrix changes as wood weathers.

PMID- 20053494
TI  - 'Secrets' that kill: crisis, custodianship and responsibility in ritual male
      circumcision in the Eastern Cape Province, South Africa.
AB  - This paper analyses a tension between traditional leaders and the post-apartheid
      government in South Africa, concerning the crisis in ritual male circumcision.
      Over the last two decades, following ritual male circumcision, thousands of youth
      have been admitted to hospitals, hundreds have undergone penile amputations and
      hundreds have died. Following the government's intervention through legislation
      and other health measures, traditional leaders allege that this is a violation of
      cultural rights enshrined in the Constitution. Drawing on newspaper and journal
      articles, books, policy documents, and legislation, as well as informal
      interviews with initiates and their parents and field observations in the Eastern
      Cape Province (2002-2009), this paper explores the validity of the traditional
      leaders' challenge, arguing that the crisis in the ritual should be seen in a
      broader context than the tension between traditional leaders and the state.
      Finally, the paper argues the tension between traditional leaders and government,
      and the sensational reporting of this by the media, unfortunately takes away
      focus from the health crisis in the ritual.

PMID- 20053495
TI  - Fetal programming of atherosclerosis: possible role of the mitochondria.
AB  - Growing evidence indicates that being small size at birth from malnutrition is
      associated with an increased risk of developing type 2 diabetes (T2D), metabolic
      syndrome and cardiovascular disease in adulthood. Atherosclerosis is common to
      these aforementioned disorders, and oxidative stress and chronic inflammation are
      now considered as initiating events in its development, with endothelial cell
      dysfunction being an early, fundamental step. According to the fetal programming
      hypothesis, growth-restricted neonates exposed to placental insufficiency exhibit
      endothelial cell dysfunction very early in life that later on predisposes them to
      atherosclerosis. Although many investigations have reported early alterations in
      vascular function in children and adolescents with low birth weight, the
      mechanisms of such fetal programming of atherosclerosis remain largely unknown.
      Experimental studies have demonstrated that low birth weight infants are
      prenatally subjected to conditions of oxidative stress and inflammation that
      might be involved in the later occurrence of atherosclerosis. Arterial
      endothelial dysfunction has been encountered in term infants, children and young
      adults with low birth weight. The loss of appropriate endothelium function with
      decreased nitric oxide production or activity, manifested as impaired
      vasodilatation, is considered a basic step in atherosclerosis development and
      progression. Several lines of evidence indicate that mitochondrial damage is
      central to this process and that reactive oxygen species (ROS) may act as a
      double-edged sword. On the one hand, it is well-accepted that the mitochondria
      are a major source of chronic ROS production under physiological conditions. On
      the other hand, it is known that ROS generation damages lipids, proteins and
      mitochondrial DNA, leading to dysregulated mitochondrial function. Elevated
      mitochondrial ROS production is associated with endothelial cell dysfunction as
      well as vascular smooth muscle cell proliferation and apoptosis. Smoking,
      obesity, insulin-resistant T2D, hypercholesterolemia, hyperglycaemia and
      hypertriglyceridaemia, major, traditional precursors of atherosclerosis, are all
      linked to mitochondrial dysfunction. This review focuses on proof of in utero
      programming resulting from chronic exposure to oxidative stress and inflammation
      as a cause of atherosclerosis. Endothelial cell dysfunction may be the initial
      injury arising from adverse antenatal conditions and responsible for the early
      changes in vascular function seen in children. After considering the critical
      role of the mitochondria in atherogenesis through endothelial function
      abnormalities, we propose that placental mitochondrial dysfunction is present in
      cases of placental insufficiency and may be critical in fetal programming of
      atherosclerosis.

PMID- 20053496
TI  - Differential diagnosis of intracranial ring enhancing cystic mass lesions--role
      of diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI).
AB  - OBJECTIVE: To evaluate the contribution of DWI and DTI to the differential
      diagnosis of cerebral ring enhancing lesions by describing DWI and ADC (apparent
      diffusion coefficient) findings and measuring the two DTI parameters mean
      diffusivity (MD) and fractional anisotropy (FA). MATERIALS AND METHODS: A total
      of 17 patients presenting with 26 rim enhancing cysts were investigated with DWI
      and DTI. Parameter maps of the DTI metrics MD and FA were calculated and
      quantified using regions of interest (ROIs). RESULTS: Five patients suffered from
      abscesses with a total of 10 cysts, 9 from glioblastomas with 10 cysts, and 3
      from metastases with 6 cysts. All abscess cavities showed hyperintense DWI signal
      intensity compared to normal appearing white matter (NAWM), low ADC, low MD and
      high FA. Eight out of 10 glioblastoma cysts and all 6 metastatic cysts revealed
      hypointensity on DWI, high ADC, high MD and low FA (p<0.0001 compared to abscess
      group). DWI findings of 2/10 glioblastoma cysts overlapped with those of
      abscesses showing hyperintensity on DWI, low ADC and low MD and hence mimicked
      abscesses. FA of these 2 glioblastoma cysts was significantly lower than in
      abscess cavities (p=0.032). CONCLUSION: The findings of reduced diffusion
      compared to NAWM and increased FA within a ring enhancing cyst strongly indicate
      a cerebral abscess. In contrast, the majority of neoplastic cysts revealed high
      diffusion and low FA. Reduced diffusion is also found in a very small number of
      tumour cysts, but in these low FA refers to a non-infectious origin and thus
      helps distinguishing from infectious abscess.

PMID- 20053497
TI  - Inhibition of growth and motility of human A549 lung carcinoma cells by a
      recombined vascular basement membrane derived peptide.
AB  - We have previously constructed a recombined vascular basement membrane derived
      multifunctional peptide (rVBMDMP) which can inhibit tumor growth. The aim of this
      study is to explore the effects and mechanisms of rVBMDMP on growth and
      motility/invasion in human A549 lung carcinoma cells. The effect of rVBMDMP on
      A549 cell viability was determined by MTT assay while the motility/invasion was
      measured by scratch and transwell assays. Molecules that responded to rVBMDMP
      treatment of A549 cells were explored using the high-throughput Cancer Pathway
      Finder cDNA Microarray. We identified 16 genes that were up-regulated, including
      GZMA, ITG alphaV, MCAM and Kiss1 and 21 genes that were down-regulated, including
      uPA, uPAR, CDC25A, IGF1 and FGF2. Selective differentially expressed genes were
      further analyzed by real-time quantitative PCR and Western blot analysis. These
      findings contribute to the understanding of the molecular mechanisms mediating
      rVBMDMP action, and suggest that rVBMDMP is a promising novel agent for the
      treatment of human lung carcinoma.

PMID- 20053498
TI  - Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to
      suppression of proliferation and chemosensitization of human hepatocellular
      carcinoma cells.
AB  - Constitutive activation of STAT3 has been shown in several human cancers and
      transformed cell lines including hepatocellular carcinoma (HCC). In the present
      report, we investigated whether diosgenin, a steroidal saponin isolated from
      fenugreek can modulate the STAT3 signaling pathway. We found that diosgenin
      inhibited both constitutive and inducible activation of STAT3 with no effect on
      STAT5. The activation of c-Src, JAK1 and JAK2 implicated in STAT3 activation,
      were also suppressed by this saponin. Pervanadate reversed the diosgenin-induced
      downregulation of STAT3, suggesting the involvement of a protein tyrosine
      phosphatase. Indeed, we found that diosgenin can induce the expression of Src
      homology 2 phosphatase 2 (SH-PTP2) that correlated with downregulation of
      constitutive STAT3 activation. Diosgenin also downregulated the expression of
      various STAT3-regulated gene products, inhibited proliferation and potentiated
      the apoptotic effects of paclitaxel and doxorubicin. Overall, these results
      suggest that diosgenin is a novel blocker of the STAT3 activation pathway, with a
      potential role in the treatment of HCC and other cancers.

PMID- 20053499
TI  - Ex situ bioremediation of oil-contaminated soil.
AB  - An innovative bioprocess method, Systematic Environmental Molecular
      Bioremediation Technology (SEMBT) that combines bioaugmentation and
      biostimulation with a molecular monitoring microarray biochip, was developed as
      an integrated bioremediation technology to treat S- and T-series biopiles by
      using the landfarming operation and reseeding process to enhance the
      bioremediation efficiency. After 28 days of the bioremediation process, diesel
      oil (TPH(C10-C28)) and fuel oil (TPH(C10-C40)) were degraded up to approximately
      70% and 63% respectively in the S-series biopiles. When the bioaugmentation and
      biostimulation were applied in the beginning of bioremediation, the microbial
      concentration increased from approximately 10(5) to 10(6) CFU/g dry soil along
      with the TPH biodegradation. Analysis of microbial diversity in the contaminated
      soils by microarray biochips revealed that Acinetobacter sp. and Pseudomonas
      aeruginosa were the predominant groups in indigenous consortia, while the
      augmented consortia were Gordonia alkanivorans and Rhodococcus erythropolis in
      both series of biopiles during bioremediation. Microbial respiration as
      influenced by the microbial activity reflected directly the active microbial
      population and indirectly the biodegradation of TPH. Field experimental results
      showed that the residual TPH concentration in the complex biopile was reduced to
      less than 500 mg TPH/kg dry soil. The above results demonstrated that the SEMBT
      technology is a feasible alternative to bioremediate the oil-contaminated soil.

PMID- 20053501
TI  - Fasciola hepatica: histological changes in the reproductive structures of
      triclabendazole (TCBZ)-sensitive and TCBZ-resistant flukes after treatment in
      vivo with TCBZ and the related benzimidazole derivative, Compound Alpha.
AB  - Twenty-four shed-reared lambs were each infected orally with 250 metacercariae of
      Fasciola hepatica, using either the triclabendazole (TCBZ)-sensitive Cullompton
      isolate or the TCBZ-resistant Sligo isolate. Twelve weeks after infection the
      lambs were treated with TCBZ (10mg/kg) or with the experimental fasciolicide,
      Compound Alpha (Cpd alpha), a benzimidazole derivative of TCBZ (15mg/kg). The
      lambs were euthanised 48, 72 and 96h after TCBZ treatment, or 24, 48 and 72h
      after Cpd alpha treatment, and flukes were collected from the liver and/or gall
      bladder of each animal. Untreated animals harbouring 12-week infections were
      euthanized 24h after administration of anthelmintic to the treatment groups, and
      the untreated flukes provided control material. A semi-quantitative assessment of
      the degree of histological change induced by the two drugs after different times
      of exposure was achieved by scoring the intensity of three well-defined lesions
      that developed in the testes and uteri of a representative sample of flukes from
      each lamb. In general, it was found that in those tissues where active meiosis
      and/or mitosis occurred (testis, ovary, and vitelline follicles), there was
      progressive loss of cell content due to apparent failure of cell division to keep
      pace with expulsion of the mature or effete products. Further, actively dividing
      cell types tended to become individualised, rounded and condensed, characteristic
      of apoptotic cell death. Protein synthetic activity was apparently inhibited in
      the Mehlis' secretory cells. In the uterus, where successful formation of shelled
      eggs represents the culmination of a complex sequence of cytokinetic, cytological
      and synthetic activity involving the vitelline follicles, the ovary and the
      Mehlis' gland, histological evidence indicating failure of ovigenesis was evident
      from 24h post-treatment onwards. The development of these lesions may be related
      to the known anti-tubulin activity of the benzimidazole class of anthelmintics,
      to the induction of apoptosis in cells where mitosis or meiosis has aborted due
      to failure of spindle formation, and to drug-induced inhibition of protein
      synthesis. The semi-quantitative findings indicated that Cpd alpha is slightly
      less efficacious than TCBZ itself in causing histological damage to the
      reproductive structures of TCBZ-sensitive flukes, and that, like TCBZ, it caused
      no histological damage in flukes of the TCBZ-resistant isolate. This study
      illustrates the potential utility of histological techniques for conveniently
      screening representative samples of flukes in field trials designed to validate
      instances of drug resistance or to test the efficacy of new products against
      known drug-resistant and drug-susceptible fluke isolates. It also provides
      reference criteria for drug-induced histopathological changes in fluke
      reproductive structures which may aid interpretation of TEM findings.

PMID- 20053502
TI  - The impact of milk handling procedures on Ostertagia ostertagi antibody ELISA
      test results.
AB  - The impact of various milk handling stressors were analyzed using a commercially
      available enzyme-linked immunosorbent assay (ELISA) test measuring Ostertagia
      ostertagi antibodies in milk from dairy cattle (Svanovir). An indirect ELISA has
      the ability to determine the amount of milk production losses related to
      intestinal parasitism. The ELISA test recommends fresh defatted milk, however,
      milk collected from Dairy Herd Improvement (DHI) programs in North America
      undergo many stressors, including, heating, freezing and are not defatted.
      Normalized optical density ratios (ODRs) were compared between fresh defatted
      milk and milk subjected to one or more stressors with a linear mixed model
      accounting for differences in variation between the fresh and the frozen samples.
      Concordance correlation coefficients were also analyzed for comparisons to other
      similar studies. After accounting for random cow and container effects, the
      treatment factors interacted with each other (p<0.001). Biologically interesting
      contrasts were created to explain the interaction. The estimated difference in
      ODR between the milk samples handled according to recommendations of the
      manufacturers of Svanovir and the whole milk samples that were subjected to the
      most extreme treatment (heated, frozen, thawed, and re-frozen for 4 weeks) was
      0.062 (p<0.001). This difference represented less than 5% of the range, and was
      thus considered biologically negligible. Frozen whole milk processed by DHI
      programs, the most likely method of collecting on-farm samples in North America,
      will likely yield reliable results for the indirect ELISA tests, particularly,
      Svanovir.

PMID- 20053504
TI  - Trigeminal neuralgia may be caused by abnormality of the trigger zone.
AB  - Trigeminal neuralgia is a painful unilateral neuralgia of the trigeminal nerve
      characterized by agonizing, paroxysmal, and lancinating facial pain with
      unidentified causes. Usually it is triggered by stimuli at specific area in head
      or neck which is called trigger zone clinically. The pathophysiology of
      trigeminal neuralgia is thought to be focal mechanical compression of the
      trigeminal nerve at a point close to the brain stem, but also not quite clear.
      Unclear causes lead to unidentified treatments. Most therapeutic methods are
      simply symptomatic treatment. Many medicine and treatment methods have been
      proved effective, such as carbamazepine, gabapetin, phenytoin, microvascular
      decompression, percutaneous techniques and radiosurgery methods, but their long
      term efficiency remains a matter of dispute. Therefore, novel etiological and
      therapeutic concepts are urgently needed. According to our clinical observation
      and some facts that do not favor the mechanical compression theory, such as
      epidemiological analysis, clinical manifestation and pathoanatomical characters
      of trigeminal neuralgia, we can conclude that not all trigeminal neuralgia is
      related to mechanical compression, some may be caused by abnormality of receptors
      or nerve endings in the trigger zone. Based on this hypothesis, we make the
      hypotheses that subcutaneous or submucous injection of carbamazepine at the
      position of trigger zone might be more effective than taking carbamazepine orally
      as we usually do. We also make further hypotheses that destruction of trigger
      zone such as by laser, freezing or surgery may be a novel and effective treatment
      methods for trigeminal neuralgia.

PMID- 20053503
TI  - The reliability and validity of drug users' self reports of amphetamine use among
      primarily heroin and cocaine users.
AB  - Relatively few studies have addressed the psychometric properties of self-report
      measures of amphetamine use. This study examines the reliability and validity of
      the Risk Behavior Assessment's (RBA) lifetime and recent amphetamine-use
      questions. To evaluate validity, 4027 out-of-treatment primarily cocaine and
      heroin users provided urine samples that were compared to self-report data; to
      evaluate reliability, 218 completed the RBA at two time points, 48h apart. In the
      overall sample, self-reports demonstrated moderately high validity, with a 95%
      accuracy rate (kappa=.54). When analysis was restricted to recent amphetamine
      users validity was slightly lower (71.5% accuracy; kappa=.41). Test-retest data
      indicated good reliability for self-reports of ever having used amphetamine
      (kappa=.79), and amphetamine use in the past 30 days (.75<r<.91). Out-of
      treatment drug users provided accurate self-reports of amphetamine use. Reliable
      and valid measures are essential for describing and predicting trends in
      amphetamine use, evaluating the effectiveness of interventions, and developing
      policies and programs.

PMID- 20053505
TI  - A molecular analysis of European porcine reproductive and respiratory syndrome
      virus isolated in South Korea.
AB  - In a situation where European genotype of porcine reproductive and respiratory
      syndrome virus (PRRSV) has recently emerged in South Korea, this study aims to
      understand variations in and relatedness among 25 European (EU) genotype 1 PRRSV
      isolates obtained from Korean pig farms during the period ranging from 2006 to
      2009 for their sequences of nonstructural protein 2 (NSP2), open reading frames
      (ORF) 5 and 7, which, in turn, were compared with those of published Korean type
      1 PRRSV isolates (CP6874, IV3140 and KNU07) and other EU PRRSV strains. The
      sequence data revealed that all Korean type 1 isolates were found to possess
      notable 19 amino acid deletions within NSP2 between positions 748 and 766. Based
      on the complete ORF5 sequences, the results showed that the Korean isolates
      amounted to 82.0-99.5% in amino acid identity with one another, while sharing a
      lower level of amino acid identity ranging from 71.6% to 92.0% with EU genotype
      strains isolated in other geographic areas. According to an amino acid sequence
      comparison of ORF7, the level of identity among the Korean type 1 isolates was
      found to range from 86.7% to 100%. Phylogenetic analyses based on ORF5 and ORF7
      sequences indicated that the Korean type 1 isolates belonged to the pan-European
      subtype 1; in ORF5 phylogeny, they form three distinct clusters from other EU
      genotype PRRSV strains. In conclusion, those findings suggest that the Korean
      type 1 PRRSV may have undergone a high degree of variations since EU genotype
      virus was first detected.

PMID- 20053506
TI  - Effects of storage methods on the recovery of Mycoplasma species from milk
      samples.
AB  - Mycoplasma species are fastidious microorganisms causing mastitis in dairy cows.
      Storage by freezing milk samples affects their viability. The purpose of this
      study was to compare the effect of alternative storage methods on their
      recoverability. In Experiment I, mycoplasma counts from fresh milk samples were
      compared to those same samples stored for 1, 3, and 5 days at refrigerated (5
      degrees C) temperatures. Experiment II was done to compare the mycoplasma counts
      of fresh milk samples with those stored frozen (-20 degrees C) with addition of
      0%, 10%, 30% and 50% glycerol (v/v). Two strains of each of 5 species: M. bovis,
      M. californicum, M. bovigenitalium, M. canadense and M. alkalescens, were
      selected and inoculated into bulk tank milk free of this pathogen. Compared to
      those in fresh milk samples, counts were approximately reduced by: 0.3
      log(10)CFU/ml in 5 day refrigerated milk (P<0.05) and by 1.0 log(10)CFU/ml in
      milk frozen without glycerol (P<0.05). Addition of glycerol (10% and 30%, v/v) to
      milk samples increased the number of recovered Mycoplasma by up to 0.4
      log(10)CFU/ml in frozen milk samples (P<0.05). No significant interactions were
      detected between either Mycoplasma species or starting concentration and survival
      as effected by storage method. Refrigerating milk samples for 5 days and freezing
      milk samples lowers the number of recovered Mycoplasma species. The addition of
      glycerol to achieve 10% and 30% v/v solutions improves the recovery of Mycoplasma
      species from frozen milk samples. To maximize detection of this pathogen, fresh
      milk samples should be cultured without storage.

PMID- 20053507
TI  - Up-regulation of the MyD88-dependent pathway of TLR signaling in spleen and
      caecum of young chickens infected with Salmonella serovar Pullorum.
AB  - TLR signaling plays a role in Salmonella infection, but less information is
      available in chickens infected with Salmonella serovar Pullorum. The present
      study with young chickens, experimentally infected with S. Pullorum, has used
      real-time quantitative RT-PCR to investigate the relative expression of genes of
      the TLR4 signaling pathway (TLR4, MyD88, TRAF6 and NF-kappaB) in the spleen and
      caecum at 1, 3, 7 and 14 days post-infection (dpi). Three-day-old specific
      pathogen-free chickens were orally infected with S. Pullorum or saline
      (controls). In addition to gene expression, the bacterial burden of spleen and
      caecum was assessed and serum concentrations and total IgG were measured.
      Significantly more bacteria were found in the caecum than in the spleen.
      Concentrations of IgG were significantly higher in infected birds at 1 dpi,
      reached a peak at 3 dpi (P<0.01), and then gradually decreased with the time.
      Infected young chickens had significant up-regulation of the expression of TLR4,
      MyD88, TRAF6 and NF-kappaB in the spleen at 3 dpi compared to controls (P<0.05).
      In the caecum, only increased expression of NF-kappaB mRNA (P<0.05) was observed
      at 1 dpi. The pattern of immune response to infection with S. Pullorum differed
      between spleen and caecum and did not directly correspond with pathogen burden.
      The observed changes indicate that the MyD88-dependent pathway of TLR4 signaling
      plays a role in young chickens infected with S. Pullorum.

PMID- 20053508
TI  - Development and validation of a SIgA-ELISA for the detection of Mycoplasma
      hyopneumoniae infection.
AB  - An alternative indirect enzyme-linked immunosorbent assay (ELISA) for the
      detection of Mycoplasma hyopneumoniae secretory IgA (SIgA) antibody (SIgA-ELISA)
      was developed using an adhesin (P97R1) of M. hyopneumoniae produced in
      Escherichia coli. The SIgA-ELISA assay was validated by the comparison with a
      nested-PCR assay and a commercial M. hyopneumoniae antibody detection kit (IgG
      ELISA). Two hundred and sixty nasal swab samples, bronchoalveolar lavage fluids
      or serum samples were prepared for SIgA-ELISA validation from a M. hyopneumoniae
      free farm, a M. hyopneumoniae vaccinated farm and two M. hyopneumoniae
      contaminated farms. The results showed that the SIgA-ELISA assay could
      distinguish the M. hyopneumoniae infection from M. hyopneumoniae vaccinated pigs,
      which was impossible for the current commercial M. hyopneumoniae antibody
      detection kits. The diagnostic sensitivity (DSN), specificity (DSP) and accuracy
      of the SIgA-ELISA were 97.0%, 94.4% and 95.8%, respectively and were compared
      with nested-PCR on 260 field nasal swab samples. The results of repeatability
      tests revealed that the coefficients of variation of swab samples within and
      between runs were less than 10%. This SIgA-ELISA is a needle-free detection
      methodology for large-scale surveys of M. hyopneumoniae infection.

PMID- 20053509
TI  - Equine influenza outbreak in India (2008-09): virus isolation, sero-epidemiology
      and phylogenetic analysis of HA gene.
AB  - An outbreak of equine influenza (EI) was reported in India in June, 2008 after a
      gap of two decades. The outbreak started from Jammu and Kashmir (Katra), northern
      state of India and spread to the other parts of the country affecting equines in
      11 states. The virus (H3N8) was isolated from nasal swabs obtained from clinical
      cases in various locations in the country including Katra (Jammu and Kashmir),
      Mysore (Karnataka) and Ahmedabad (Gujarat) using embryonated chicken eggs. The
      virus isolates were identified as H3N8 by haemagglutination inhibition (HI) test
      titration with standard serum and by sequencing of full-length haemagglutinin
      (HA) gene and partial sequence of neuraminidase (NA) gene. Paired serum samples
      (n=271) showing more than fourfold rise in antibody titres tested from 11 states
      confirmed equine influenza. Serum samples (n=2517) of equines from 13 states of
      the country screened by HI test revealed 687 (26.85%) samples positive for
      antibodies to EI (H3N8). Phylogenetic analysis of the haemagglutinin (HA) gene
      confirmed the virus to be closely related to Clade 2 of the Florida sublineage in
      American lineage. Comparison of deduced amino acid sequence of HA gene with EIV
      isolates from various lineages showed substitutions in the antigenic regions C
      and D. HA1 gene sequence had highest amino acid identity to A/eq/Gansu/7/08 and
      A/eq/Hubei/6/08 isolates from China and Inner-Mongolia isolate, while the
      complete HA gene sequence was closest to A/eq/A/eq/Newmarket/5/03, A/eq/Bari/05
      and A/eq/Kentucky/05/02 isolates. Recent outbreaks of Mongolia, China and India
      by clade 2 EI viruses imply their predominance in Asia in addition to Europe.

PMID- 20053510
TI  - Child developmental screening instrument from six to thirty-six months in Taiwan
      birth cohort study.
AB  - BACKGROUND: A reliable and valid assessing tool to detect the problem before the
      child becomes deviant is very important. AIM: This study aimed to further test
      the reliability and validity of developmental screening instrument for follow-up
      of thirty-six months children in Taiwan. Also, the stability and changes in the
      development of children from six to thirty-six months were investigated. METHODS:
      A total of 1751 infants were administered the six-month scale, which included
      levels of Gross and Fine Motor, Language/Communication, and Social ability. At
      eighteen months, 1267 infants were followed up, and at thirty-six months, 1630
      infants were followed up. RESULTS: Item analysis showed the thirty-six months
      scale had a Cronbach's alpha of 0.793. By confirmatory factor analysis, the
      correlations of the four dimensions in this scale were within the range of 0.38
      to 0.61. Structural equation modeling showed that the six month scale could
      directly predict the eighteen months scale, and the gross motor, language, and
      social dimensions in the thirty-six months scale. The eighteen-month scale was
      also predictive of the thirty-six months scale. The six, eighteen and thirty-six
      month scales all had acceptable reliability and validity, including content,
      construct and predictive validity. Additionally, the language development at six
      months was predictive of the language and social development at thirty-six
      months. The predictive model showed there were correlations between each
      dimensions at different ages. CONCLUSIONS: This study is the pilot of a large and
      scientifically robust longitudinal first national birth cohort study in Taiwan,
      and the findings should provide useful reference for future studies.

PMID- 20053511
TI  - Environmental and sow-related factors affecting the duration of farrowing.
AB  - A short duration of farrowing is important for piglet survival as a delay can
      increase the number of stillborn. Many factors may affect the duration of
      farrowing, including breed, age of the sow, length of gestation, number of
      piglets born, housing (CRATE vs. PEN), body condition of the sow and state of
      constipation. The aim of the present study was to investigate these factors and
      how they interact with each other and thus increasing the risk of prolonged
      farrowing. The total duration of farrowing and average piglet birth interval were
      recorded in 172 sows from two herds (HERD-1, n = 76; HERD-2, n = 96). Back-fat
      measurements and intestinal activity (based on the mean of a constipation index)
      were measured in all 172 sows. The total duration of farrowing was 272 +/- 152
      min (mean +/- SD, n = 172): 301 +/- 165 min (n = 115) in the CRATE group and 212
      +/- 95 min (n = 57; P < 0.05) in the PEN group. The average piglet birth interval
      was 26 +/- 25 min (mean +/- SD, n = 172): 29 +/- 29 min (n = 115) in the CRATE
      group and 19 +/- 10 min (n = 57; P < 0.05) in the PEN group. Housing (P < 0.05),
      stillborn (P < 0.001), back-fat average (P < 0.001) and constipation index (P <
      0.05) significantly correlated with the duration of farrowing. In conclusion,
      allowing the sow to move freely before farrowing, reducing the constipation state
      and avoid excessive fattening during late pregnancy all appear to be key factors
      in shortening farrowing time and reducing perinatal mortality.

PMID- 20053512
TI  - Evaluation of a natural health product decision aid: a tool for middle aged women
      considering menopausal symptom relief.
AB  - OBJECTIVE: To evaluate the effectiveness of a self-administered decision aid for
      menopausal women facing decisions about natural health products. STUDY DESIGN:
      This pre-/post-test study included peri- or post-menopausal women, aged 45-64
      considering the use of a natural health product for management of menopausal
      symptoms. They were recruited from a Women's Health Center. OUTCOME MEASURES: The
      primary outcome was decisional conflict and secondary outcomes included
      knowledge, strength of values, and decision preference. RESULTS: Of 24 women, the
      typical participant was 50-64 years of age, Caucasian, married, and well
      educated. Compared to baseline, after using the decision aid, women's total
      decisional conflict was reduced from 63% to 24% (p<0.001) and knowledge improved
      from 76% to 87% (p=0.001). Of the 24 women, 10 were unsure of their choice at
      baseline and 3-post use of the decision aid (p=0.015). There was a trend for
      women preferring natural health products (n=12) to be more likely to rate the non
      chemical aspect as important and the cost of the natural health product as less
      important; women who preferred not to take natural health products (n=3) rated
      the non-chemical aspect as less important and the costs as more important.
      CONCLUSIONS: The natural health product decision aid improved the quality of
      decisions by enhancing knowledge and reducing decisional conflict. As well, women
      were more likely to make a choice that was consistent with their values.

PMID- 20053513
TI  - Individualizing fracture risk prediction.
AB  - Low bone mineral density (BMD) and clinical factors (CRF) have been identified as
      factors associated with an increased relative risk of fractures. From this
      observation and for clinical decision making, the concept of prediction of the
      individual absolute risk of fractures has emerged. It refers to the individual's
      risk for fractures over a certain time period, e.g. the next 5 and 10 years. Two
      individualized fracture risk calculation tools that are increasingly used and are
      available on the web are the FRAX algorithm and the Garvan fracture risk
      calculator. These tools integrate BMD and CRFs for fracture risk calculation in
      the individual patient in daily practice. Although both tools include
      straightforward risk factors, such as age, sex, previous fractures, body weight
      and BMD, they differ in several aspects, such as the inclusion of other CRFs,
      fall risks and number of previous fractures. Both models still need to be
      validated in different populations before they can be generalized to other
      populations, since the background risk for fractures is population specific.
      Further studies will be needed to validate their contribution in selecting
      patients who will achieve fracture risk reduction with anti-osteoporosis therapy.

PMID- 20053514
TI  - Balloon catheter assisted excision of benign cervical cyst.
AB  - OBJECTIVES: Benign cystic masses that develop in the neck are easily excised with
      a wide skin incision. However, if the cyst is perforated and the contour of the
      cyst is not maintained during surgery, complete excision may be difficult. We
      developed a surgical method that can maintain the contour of a cyst and decrease
      the wound size with a balloon catheter. METHODS: Two cases with a branchial cleft
      cyst (BCC) were removed using this method without recurrence. The surgical
      technique includes a skin incision above the cyst, and fine dissection to expose
      the cyst wall. Then a small tap incision was created on the cyst using a #11
      blade and a #14 Fr. Foley catheter was inserted through the incision site and the
      balloon was inflated up to 4 cm(3) using normal saline. The fluid inner content
      was carefully removed keeping the intracystic balloon inflated. By pulling and
      releasing the catheter, the cyst was dissected carefully and excised. RESULTS:
      Complete excision of the cyst was performed with the balloon catheter
      successfully. The final pathological diagnosis was BCC in the two cases.
      CONCLUSIONS: The balloon-assisted technique was easy to perform and could be used
      for the excision of a benign cystic neck mass.

PMID- 20053515
TI  - Differential diagnosis of proptosis: report of 2 cases.
AB  - We rarely encounter patients with proptosis, however, it is known that
      inflammation and extension of paranasal sinus tumors may cause this condition. We
      should consider the diseases that may cause proptosis to facilitate the
      diagnosis. Recently, we treated proptosis in 2 cases, one with inflammatory
      myofibroblastic tumor (IMT) and the other with malignant lymphoma. As these 2
      diseases show various clinical features and these features frequently overlap, it
      is difficult to differentiate between IMT and malignant lymphoma without
      pathological examinations. In this study, we review the relevant literature
      reports and discuss the difficulties in establishing a clinicopathological
      diagnosis and present a slight distinction in magnetic resonance imaging.

PMID- 20053516
TI  - In vitro food-drug interaction study: Which milk component has a decreasing
      effect on the bioavailability of ciprofloxacin?
AB  - The purpose of the present work was developing an in vitro dissolution test to
      highlight the possible molecular background causing ciprofloxacin (CPFX)-milk
      interaction. The in vitro dissolution of CPFX from film-coated tablets (Ciprinol)
      500mg) was examined at different pH values, simulating certain parts of the
      gastrointestinal tract, in the presence of water, low-fat milk, casein- or
      calcium enriched water. In order to determine the amount of dissolved CPFX, solid
      phase extraction sample preparation followed by high performance liquid
      chromatography coupled with mass spectrometry was applied. Comparing the
      dissolution efficiency values in various media, it can be concluded, that casein
      has a more pronounced effect on the absorbable amount of the antibiotic at each
      pH value studied, than calcium. In the case of concomitant intake of CPFX film
      coated tablet and milk or other dairy products not only the complexation with
      calcium, but also the adsorption of CPFX on the surface of proteins decreases the
      absorbable amount of CPFX.

PMID- 20053517
TI  - A validated stability-indicating LC method for acetazolamide in the presence of
      degradation products and its process-related impurities.
AB  - The objective of the current study was to develop a validated, specific and
      stability-indicating reverse phase liquid chromatographic method for the
      quantitative determination of acetazolamide and its related substances. The
      determination was done for an active pharmaceutical ingredient, its
      pharmaceutical dosage form in the presence of degradation products, and its
      process-related impurities. The drug was subjected to stress conditions of
      hydrolysis (acid and base), oxidation, photolysis and thermal degradation as per
      International Conference on Harmonization (ICH) prescribed stress conditions to
      show the stability-indicating power of the method. Significant degradation was
      observed during acid and base hydrolysis, and the major degradant was identified
      by LC-MS, FTIR and (1)H/(13)C NMR spectral analysis. The chromatographic
      conditions were optimized using an impurity-spiked solution and the generated
      samples were used for forced degradation studies. In the developed HPLC method,
      the resolution between acetazolamide and, its process-related impurities (namely
      imp-1, imp-2, imp-3, imp-4 and its degradation products) was found to be greater
      than 2. The chromatographic separation was achieved on a C18, 250mmx4.6mm,
      5microm column. The LC method employed a linear gradient elution, and the
      detection wavelength was set at 254nm. The stress samples were assayed against a
      qualified reference standard and the mass balance was found to be close to 99.6%.
      The developed RP-LC method was validated with respect to linearity, accuracy,
      precision and robustness.

PMID- 20053518
TI  - Can interactive skills-based seminars with standardized patients enhance
      clinicians' prevention skills? Measuring the impact of a CME program.
AB  - OBJECTIVE: Communication skills are crucial for high-risk behavior screening and
      counseling. Practicing physicians have limited opportunities to improve these
      skills. This paper assesses the impact of a continuing medical education (CME)
      program for Student Health Center clinicians that targeted communication skills,
      screening practices and patient satisfaction. METHODS: Program evaluation
      included pre- and post-objective structured clinical examinations (OSCE's), chart
      review, and provider and patient satisfaction surveys. Data were analyzed using
      paired t-tests and ranked sum tests. RESULTS: OSCE scores (n=15) revealed
      significant improvements in communication skills overall (p=0.004) and within
      specific domains (data gathering: p=0.003; rapport building: p=0.01; patient
      education: p=0.02), but no change in case-specific knowledge (p=0.1).
      Participants (n=14) reported high satisfaction with program methods (mean=4.6/5)
      and content (mean=4.7/5), 70% planning to alter their clinical practice. Chart
      audits (pre=96, post=103) showed increased screening for smoking (RR 1.65,
      p=0.03), depressed mood (RR 1.40, p=0.04), anhedonia (RR 1.47, p=0.01), sexual
      activity (RR 1.73, p=0.002) and drinking (RR 1.77, p=0.04). Sampling of
      satisfaction among participants' patients (pre n=689, post n=383) detected no
      increase in already high baseline satisfaction. CONCLUSION: This curriculum
      improved clinicians' relevant skills and screening behavior. PRACTICE
      IMPLICATIONS: Skills-oriented CME can improve clinicians' communication skills
      and screening and counseling practices.

PMID- 20053519
TI  - High-throughput caveolar proteomic signature profile for maternal binge alcohol
      consumption.
AB  - Currently, no single marker is sensitive and specific enough to be considered a
      reliable biomarker for prenatal alcohol exposure. To identify a proteomic
      signature profile for maternal alcohol consumption, we carried out high
      throughput proteomics on maternal endothelial caveolae exposed to moderate binge
      like alcohol conditions. In these specialized lipid-ordered microdomains that
      contain a rich assembly of proteins, we demonstrate that moderate binge-like
      alcohol resulted in a distinctive maternal caveolar proteomic signature with
      important proteins being dramatically decreased/knocked out in the alcoholic
      profile. These proteins span from histones and basic structural proteins like
      alpha tubulin to proteins involved in trafficking, deubiquitination, cell
      signaling, and cell-cell adhesion. The profile also suggests an important role
      for the mother and the uteroplacental compartment in the pathogenesis of fetal
      alcohol spectrum disorders (FASD). These data demonstrate that the caveolar
      proteomic signature created by alcohol shows a promising direction for early
      detection of FASD.

PMID- 20053520
TI  - Effects of moderate drinking during pregnancy on placental gene expression.
AB  - Many children adversely affected by maternal drinking during pregnancy cannot be
      identified early in life using current diagnostic criteria for fetal alcohol
      spectrum disorder (FASD). We conducted a preliminary investigation to determine
      whether ethanol-induced alterations in placental gene expression may have some
      utility as a diagnostic indicator of maternal drinking during pregnancy and as a
      prognostic indicator of risk for adverse neurobehavioral outcomes in affected
      offspring. Pregnant Long-Evans rats voluntarily consumed either a 0 or 5% ethanol
      solution 4 h each day throughout gestation. Ethanol consumption produced a mean
      maternal daily intermittent peak serum ethanol concentration of 84 mg/dL.
      Placentas were harvested on gestational day 20 for gene expression studies.
      Microarray analysis of more than 28,000 genes revealed that the expression of 304
      known genes was altered twofold or greater in placenta from ethanol-consuming
      dams compared with controls. About 76% of these genes were repressed in ethanol
      exposed placentas. Gene expression changes involved proteins associated with
      central nervous system development; organ morphogenesis; immunological responses;
      endocrine function; ion homeostasis; and skeletal, cardiovascular, and cartilage
      development. To date, quantitative real-time polymerase chain reaction analysis
      has confirmed significant alterations in gene expression for 22 genes, including
      genes encoding for three calcium binding proteins, two matrix metalloproteinases,
      the cannabinoid 1, galanin 2 and toll-like receptor 4, iodothyronine deiodinase
      2, 11-beta hydroxysteroid dehydrogenase 2, placental growth factor, transforming
      growth factor alpha, gremlin 1, and epithelial growth factor (EGF)-containing
      extracellular matrix protein. These results suggest that the expression of a
      sufficiently large number of placental mRNAs is altered after moderate drinking
      during pregnancy to warrant more detailed investigation of the placenta as a
      biomarker system for maternal drinking during pregnancy and as an early indicator
      of FASD. Furthermore, these results provide new insights into novel mechanisms on
      how ethanol may directly or indirectly mediate its teratogenic effects through
      alterations in placental function during pregnancy.

PMID- 20053521
TI  - Diagnosis of fetal alcohol spectrum disorders: a validity study of the fetal
      alcohol syndrome checklist.
AB  - Fetal alcohol spectrum disorders (FASD) are a common cause of developmental
      disability, birth defects, and mortality. The performance characteristics of
      current diagnostic tools for FASD are not adequately reported. This study
      examines the performance characteristics of the Fetal Alcohol Syndrome Diagnostic
      Checklist (FASDC). In a population of 658 subjects from North Dakota, we used the
      FASDC score to examine the agreement between FASDC score, clinical diagnosis, and
      the Institute of Medicine criteria for FASD. All subjects were seen for
      evaluation in the genetic/dysmorphology clinics, which are funded by the state to
      provide genetic diagnostic services for residents of North Dakota. We compared
      the clinical diagnosis and the FASDC scores to determine the performance
      characteristics of the FASDC in the categorical diagnosis of fetal alcohol
      spectrum (FAS), other-FASD, and a group with No-FASD. Comparisons were made using
      univariate and logistic models of outcomes using both the presence and the
      absence of alcohol exposure or FASDC phenotype data. The FASDC performance
      characteristics for differentiation of the FAS group from non-FASD were excellent
      (accuracy 99%, sensitivity 99%, and specificity 99%). Logistic models for
      subjects with scores in the FASD range were differentiated with an accuracy of
      82%, sensitivity 85%, and specificity 80% using the data on phenotype and
      exposure. We were able to delineate subjects with scores in the No-FASD range
      with an accuracy of 78%, sensitivity 64%, and specificity 81% without including
      the exposure and phenotype data by use of the other descriptive data (maternal
      characteristics, birth records, and demographic data) from the FASDC. All
      diagnostic tools should have performance characteristics assessed and available
      before adoption for use in clinical settings. The FASDC scores produce diagnostic
      groupings that approximate expert clinical judgment. The tool may be useful in
      other clinical settings for the diagnosis of FASD or as an FASD registry or
      research database.

PMID- 20053522
TI  - Validity of the T-ACE in pregnancy in predicting child outcome and risk drinking.
AB  - Preventing fetal alcohol spectrum disorders (FASDs) requires detection of in
      pregnancy maternal risk drinking. The widely used T-ACE screen has been applied
      in various ways, although the impact of those different uses on effectiveness is
      uncertain. We examined relations among different T-ACE scoring criteria, maternal
      drinking, and child outcome. Self-reported across-pregnancy maternal drinking was
      assessed in 75 African-American women. The different T-ACE criteria used varied
      the level of drinking that defined tolerance (two or three drinks) and the total
      T-ACE score cut-points (two or three). Receiver operator curves and regression
      analysis assessed the significance of relations. Increasing the total T-ACE score
      cut-point to 3 almost doubled specificity in detecting risk drinking whereas
      maintaining adequate sensitivity, equivalent to that in the original report, and
      identified substantially more neurobehavioral deficits in children. Redefining
      tolerance at three drinks did not improve T-ACE effectiveness in predicting
      outcomes. This study is among the first to show the ability of an in-pregnancy T
      ACE assessment to predict child neurodevelopmental outcome. In addition,
      increasing the total T-ACE score criterion (from 2 to 3) improved identification
      of non-drinking mothers and unaffected children with little loss in detection of
      drinkers and affected children. Efficient in-pregnancy screens for risk drinking
      afford greater opportunities for intervention that could prevent/limit FASDs.

PMID- 20053523
TI  - RNAi targeting ryanodine receptor 2 protects rat cardiomyocytes from injury
      caused by simulated ischemia-reperfusion.
AB  - The effects of a small interfering RNA targeting ryanodine receptor 2 (si-Ryr2)
      on cardiomyocytes injury following a simulated ischemia-reperfusion (I/R) were
      investigated. Pretreated with si-Ryr2 or ryanodine, primary cultures of neonatal
      rat cardiomyocytes were subjected to a protocol of simulated I/R. Compared with
      control, the cytosolic Ca(2+) concentration ([Ca(2+)](i)) and the generation of
      reactive oxygen species (ROS) was significantly augmented after I/R. Concomitant
      with these, cell injury assessed by Annexin V/PI staing, mitochondria membrane
      potential (DeltaPsim) and the leakage of lactic dehydrogenase (LDH) and creatine
      phosphokinase (CPK) were aggravated. Si-Ryr2 treatment reduced [Ca(2+)](i) and
      ROS generation and protected the cardiomyocytes from subsequent I/R injury, as
      evidenced by stable DeltaPsim and decreased Annexin V(+) PI(-) staing and enzymes
      release. Moreover, si-Ryr2 exerted more effective protection on I/R injury
      compared to ryanodine. The present study demonstrated for the first time that in
      neonatal cardiomyocytes, si-Ryr2 reduces cell death associated with attenuating
      [Ca(2+)](i) and ROS production. Furthermore, we attempt to speculate that si-Ryr2
      excel ryanodine in Ryr2 function research of cardioprotection.

PMID- 20053524
TI  - Modulation of impact of high fat diet in pathological and physiological left
      ventricular cardiac hypertrophy by fluvastatin.
AB  - The male Wistar rats were kept at high fat diet for 90 days and subjected to
      partial abdominal aortic constriction (PAAC) at 62nd and continued up to 90th
      day. Similarly, rats were kept at high fat diet for 90 days and subjected to
      chronic swimming training (CST) at 46th day and continued up to 90th day. Obesity
      was assessed by % age change in body weight, WHR ratio and adiposity index
      whereas cardiac hypertrophy was assessed by using index of cardiac hypertrophy,
      i.e., left ventricular weight, left ventricular weight to body weight, (LVW/BW),
      left ventricular wall thickness (LVWT), cardiomyocyte diameter, LV, protein
      content and collagen content. Further, mean arterial blood pressure (MABP) was
      also recorded. Oxidative stress was assessed by measuring the levels of
      thiobarbituric acid reactive species (TBARS), levels of superoxide anion
      generation and levels of reduced glutathione in left ventricular tissue. The PAAC
      and CST increased the index of cardiac hypertrophy. Moreover, PAAC has
      significantly increased MABP. Fluvastatin, 3-hydroxy-3-methylglutaryl-coenzyme A
      (HMG-CoA) reductase inhibitor, significantly attenuated PAAC induced left
      ventricular cardiac hypertrophy and MABP whereas no significant change was
      observed in CST-induced cardiac hypertrophy. Furthermore, fluvastatin
      significantly attenuated the oxidative stress by decreasing the levels of TBARS
      and superoxide anion generation and increasing the levels of reduced glutathione.
      These results suggest that fluvastatin prevented the PAAC-induced cardiac
      hypertrophy.

PMID- 20053526
TI  - Ruptured endovascular abdominal aortic aneurysm repair: part II.
AB  - Rupture of an abdominal aortic aneurysm (AAA) carries a high morbidity and
      mortality despite vast improvements in the care of critically ill patients over
      the past two decades. Between 50% and 80% of all patients with ruptured AAA do
      not survive. Endovascular treatment of ruptured AAA has recently become
      popularized because of its purported advantages to open repair in terms of
      mortality and morbidity due to its minimally invasive approach. The tabular
      review herein presented is the second part of our series on endovascular therapy
      for AAA. Similar to part 1, which emphasized elective procedures, we summarize
      the results of the world's literature for ruptured endovascular AAA repair in
      table format to serve as a comprehensive and concise search tool to be utilized
      in the vascular surgeon's and endovascular specialist's practice.

PMID- 20053525
TI  - Metformin inhibits inflammatory angiogenesis in a murine sponge model.
AB  - To investigate the effects of metformin on angiogenesis, on inflammatory cell
      accumulation and on production of endogenous cytokines in sponge implant in mice.
      Polyester-polyurethane sponges were implanted in Swiss mice and metformin (40 or
      400mg/kg/day) was given orally for six days. The implants collected at day 7
      postimplantation were processed for the assessment of hemoglobin (Hb),
      myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) e collagen used as indexes
      for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix
      deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic
      cytokines were also determined. Metformin treatment attenuated the main
      components of the fibrovascular tissue, wet weight, vascularization (Hb content),
      macrophage recruitment (NAG activity), collagen deposition and the levels of
      transforming growth factor (TGF-beta1) intraimplant. A regulatory function of
      metformin on multiple parameters of main components of inflammatory angiogenesis
      has been revealed giving insight into the potential therapeutic underlying the
      actions of metformin.

PMID- 20053527
TI  - Prehospital treatment of infrarenal ruptured abdominal aortic aneurysms: a
      multicentric analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the quality of the current
      treatment of patients presenting with ruptured abdominal aortic aneurysms
      (RAAAs), from the first symptoms to the operating room with an analysis of
      preoperative mortality risk factors. METHODS: For 3 years, in four vascular
      surgery departments, we have collected all the consecutive cases of patients
      operated on for RAAA. We analyzed the initial clinical situation, the means of
      transportation, the time elapsed before treatment, and the mortality rate at 3
      days. Sixty-six RAAAs were operated on. Mean patient age was 76 years (range, 52
      93 years). RESULTS: The initial symptoms were a precisely located pain either
      abdominal (45.3%), lumbar (17.2%), or both (14.1%) or feeling faint (10.9%). In
      22.7% of the cases, an initial hemodynamic instability was observed. In 46.8% of
      the cases, patients first went to a peripheral hospital before being admitted
      into a referral centre. In 84.5% of the cases, medical mean of transportation was
      used. The mean distance covered was 59.8 kilometers (range, <5 km to 213 km). The
      initial diagnosis was accurate in 67.3% of the cases. The mean intrahospital
      waiting period between the arrival at a reference center and the admission into
      an operating room was 127 minutes. Global mortality rate was 44.2%. The main
      preoperative mortality factor to be noticed was the initial hemodynamic
      instability (p=0.0031). Among stable patients, only two of them (5.4%) worsened
      during the preoperative treatment. CONCLUSION: In our study, hemodynamic
      instability corresponds to the main prognosis factor of mortality. In most cases,
      the initial stability persisted and allowed additional evaluation. However, the
      intrahospital waiting periods appeared to be too long. To be optimal, the
      adequate treatment should be specifically designed as soon as a diagnosis has
      been established.

PMID- 20053528
TI  - Redo arch aneurysm repair for new-onset aortic arch dissection following
      ascending aortic surgery: long elephant trunk technique combined with trifurcate
      branched graft.
AB  - Reoperative surgical intervention for a new-onset aortic arch dissection
      following a Bentall procedure or graft replacement for the ascending aorta is
      often difficult, especially in elderly patients. Herein, we report a re-do arch
      replacement method using a trifurcate-branched graft and long elephant trunk
      anastomosis at the composite root graft on the ascending aorta. The present
      technique is feasible as an alternative for new-onset or residual aortic arch
      aneurysm, as well as dissection following an operation for the ascending aorta.

PMID- 20053529
TI  - Tuberculous pseudoaneurysm of the descending thoracic aorta.
AB  - Tuberculous mycotic aortic aneurysm is a rare disease with a high mortality
      rate.(1-5) Its prevalent location is the descending thoracic aorta in the patient
      with disseminated tuberculosis. Most of these aneurysms have been of the
      pseudoaneurysm type. We report the case of a 37-year-old woman with tuberculous
      pseudoaneurym of the descending aorta that was initially mistaken for a lung
      lesion and was successfully repaired surgically.

PMID- 20053530
TI  - Internal iliac artery branch stent grafting for aortoiliac aneurysms using the
      Apollo branched device.
AB  - The association of aortic and common iliac artery aneurysms requires a special
      strategy to achieve distal seal during the endovascular exclusion of abdominal
      aortic aneurysms. Coil embolization of the internal iliac artery before the
      placement of a bifurcated endograft limb into the external iliac artery is a
      usual option. Such procedures are usually well tolerated but may result in
      buttock claudication, postprocedural sexual dysfunction, and colonic ischemia. We
      report on an alternative repair to preserve internal iliac artery patency using
      the Apollo iliac branched device.

PMID- 20053531
TI  - Sequential reconstruction of vessel skeletons from X-ray coronary angiographic
      sequences.
AB  - X-ray coronary angiography (CAG) is one of widely used imaging modalities for
      diagnosis and interventional treatment of cardiovascular diseases. Dynamic CAG
      sequences acquired from several viewpoints record coronary arterial morphological
      information as well as dynamic performances. The aim of this work is to propose a
      semi-automatic method for sequentially reconstructing coronary arterial skeletons
      from a pair of CAG sequences covering one or several cardiac cycles acquired from
      different views based on snake model. The snake curve deforms directly in 3D
      through minimizing a predefined energy function and ultimately stops at the
      global optimum with the minimal energy, which is the desired 3D vessel skeleton.
      The energy function combines intrinsic properties of the curve and acquired image
      data with a priori knowledge of coronary arterial morphology and dynamics.
      Consequently, 2D extraction, 3D sequential reconstruction and tracking of
      coronary arterial skeletons are synchronously implemented. The main advantage of
      this method is that matching between a pair of angiographic projections in point
      by-point manner is avoided and the reproducibility and accuracy are improved.
      Results are given for clinical image data of patients in order to validate the
      proposed method.

PMID- 20053532
TI  - Epigenetics and autoimmunity.
AB  - Advances in genetics, such as sequencing of the human genome, have contributed to
      identification of susceptible genetic patterns in autoimmune diseases (AID).
      However, genetics is only one aspect of the diseases that does not reflect the
      influence of environment, sex or aging. Epigenetics, the control of gene
      packaging and expression independent of alterations in the DNA sequence, is
      providing new directions linking genetics and environmental factors. Recent
      findings have contributed to our understanding of how epigenetic modifications
      could influence AID development, showing differences between AID patients and
      healthy controls but also showing how one disease differs from another. With
      regards to epigenetic abnormalities, DNA methylation and histone modifications
      could be affected leading to large spatial and temporal changes in gene
      regulation. Other epigenetic processes, such as the influence of the ionic milieu
      around chromatin and DNA supercoiling stresses may be suspected also. The newly
      described role of microRNAs in control of gene expression is important by
      promoting or suppressing autoreactivity in AID. As a consequence control of
      cellular processes is affected becoming conducive, for example, to the
      development of autoreactive lymphocytes in systemic lupus erythematosus,
      synoviocyte proliferation in rheumatoid arthritis, or neural demyelination in
      multiple sclerosis. Application of epigenetics to AID is in its infancy and
      requires new hypotheses, techniques, tools, and collaborations between basic
      epigenetic researchers and autoimmune researchers in order to improve our
      comprehension of AID. From this will arise new therapeutics, means for early
      intervention, and perhaps prevention.

PMID- 20053534
TI  - Perioperative metabolic changes in patients undergoing cardiac surgery.
AB  - Perioperative metabolic changes in cardiac surgical patients are not only induced
      by tissue injury and extracorporeal circulation per se: the systemic inflammatory
      response to surgical trauma and extracorporeal circulation, perioperative
      hypothermia, cardiovascular and neuroendocrine responses, and drugs and blood
      products used to maintain cardiovascular function and anesthesia contribute to
      varying degrees. The pathophysiologic changes include increased oxygen
      consumption and energy expenditure; increased secretion of adrenocorticotrophic
      hormone, cortisol, epinephrine, norepinephrine, insulin, and growth hormone; and
      decreased total tri-iodothyronine levels. Easily measurable metabolic
      consequences of these changes include hyperglycemia, hyperlactatemia, increased
      aspartate, glutamate and free fatty acid concentrations, hypokalemia, increased
      production of inflammatory cytokines, and increased consumption of complement and
      adhesion molecules. Nutritional risk before elective cardiac surgery-defined as
      preoperative unintended pathologic weight loss/low amount of food intake in the
      preceding week or low body mass index-is related to adverse postoperative
      outcome. Improvements in surgical techniques, anesthesia, and perioperative
      management have been designed to minimize the stressful stimulus to catabolism,
      thereby slowing the wasting process to the point where much less nutrition is
      required to meet metabolic requirements. Early nutrition in cardiac surgery is
      safe and well tolerated.

PMID- 20053533
TI  - Association of glycemic load with cardiovascular disease risk factors: the
      Women's Health Initiative Observational Study.
AB  - OBJECTIVE: Associations between dietary glycemic load (GL) and cardiovascular
      disease risk factors, including plasma lipoprotein/lipid levels, blood pressure,
      and glucose metabolism factors, in the Women's Health Initiative Observational
      Study were examined. METHODS: A random sample of 878 Observational Study
      participants (postmenopausal women 50-79 y of age) with baseline blood
      measurements (647 white, 104 black, 127 Hispanic) was included. Dietary GL was
      estimated from baseline food-frequency questionnaires, which assessed dietary
      intake over the previous 3 mo. At the baseline visit, participants completed
      demographic and health habit questionnaires, fasting blood samples were
      collected, anthropometric measurements were completed, and blood pressure was
      assessed. RESULTS: In all participants combined, GL was inversely associated with
      high-density lipoprotein cholesterol (P for trend = 0.004) and positively
      associated with log(10)-transformed triacylglycerols (P = 0.008). Although there
      were no statistically significant interactions of race/ethnicity with
      associations between GL and cardiovascular disease risk factors, stratified
      results were suggestive, showing that GL was positively associated with total
      cholesterol (P = 0.018) and low-density lipoprotein cholesterol (P = 0.038) in
      Hispanics. In white subjects, there was a trend of reduced high-density
      lipoprotein cholesterol with higher GL (P = 0.003), whereas GL was positively
      associated with log(10)-transformed triacylglycerols (P = 0.015). Associations
      between GL and high-density lipoprotein cholesterol and between GL and
      triacylglycerols also differed by body mass index, although the interactions were
      not statistically significant. CONCLUSION: Among these generally healthy
      postmenopausal women, GL was associated with high-density lipoprotein cholesterol
      and triacylglycerols. Suggestive effects of race/ethnicity and body mass index on
      these associations need to be confirmed in larger studies.

PMID- 20053535
TI  - Extra-capsular dissection for benign parotid tumours.
AB  - The most common benign tumour of the parotid is pleomorphic adenoma (PA). Some
      studies have shown that limited surgery to manage these types of tumours is
      viable option. Extra-capsular dissection (ECD) is one of these minimally invasive
      techniques. This study aimed to evaluate the morbidity associated with ECD in
      managing benign parotid tumours and to demonstrate that the technique can be used
      outside specialist centres. Twenty-six consecutive patients, diagnosed with
      benign parotid gland tumours were treated by ECD. Their benign status was
      determined by history, clinical criteria and fine needle aspiration cytology.
      Inclusion criteria were a discrete mobile lump, more than 3 cm in diameter and
      clinical/histological evidence of benign biological behaviour. A single surgeon
      (the author) operated on all cases. Follow up ranged from 2 to 72 months. In 23
      patients, the tumour was located entirely within the superficial lobe of the
      parotid. Postoperative pathology consisted mainly of 17 PA. Fifteen percent had
      transient damage to the facial nerve. None had recurrence. ECD seems to be an
      alternative to superficial parotidectomy for most superficial parotid lumps. It
      appears to be a safe technique in trained hands.

PMID- 20053536
TI  - The interaction of working memory and emotion in persons clinically at risk for
      psychosis: an fMRI pilot study.
AB  - Subtle emotional and cognitive dysfunctions may already be apparent in
      individuals at risk for psychosis. However, there is a paucity of research on the
      neural correlates of the interaction of both domains. It remains unclear whether
      those correlates are already dysfunctional before a transition to psychosis. We
      used functional magnetic resonance imaging to examine the interaction of working
      memory and emotion in 12 persons clinically at high risk for psychosis (CHR) and
      12 healthy subjects individually matched for age, gender and parental education.
      Participants performed an n-back task while negative or neutral emotion was
      induced by olfactory stimulation. Although healthy and psychosis-prone subjects
      did not differ in their working memory performance or the evaluation of the
      induced emotion, decreased activations were found in CHR subjects in the superior
      parietal lobe and the precuneus during working memory and in the insula during
      emotion induction. Looking at the interaction, CHR subjects, showed decreased
      activation in the right superior temporal gyrus, which correlated negatively with
      psychopathological scores. Decreased activation was also found in the thalamus.
      However, an increase of activation emerged in several cerebellar regions.
      Dysfunctions in areas associated with controlling whether incoming information is
      linked to emotional content and in the integration of multimodal information
      might lead to compensatory activations of cerebellar regions known to be involved
      in olfactory and working memory processes. Our study underlines that cerebral
      dysfunctions related to cognitive and emotional processes, as well as their
      interaction, can emerge in persons with CHR, even in absence of behavioral
      differences.

PMID- 20053538
TI  - Do atypical antipsychotic drugs reduce the risk of ischemic heart disease and
      mortality? Possible role of 5-HT2A receptor blockade.
AB  - A recent Finnish study reported that long-term cumulative exposure to any
      antipsychotic treatment was related to lower mortality than was no drug exposure.
      We hypothesize that the antipsychotic 5-HT2A receptor blockade might protect from
      ischemic heart disease and buffer the deleterious metabolic effects of
      antipsychotics. The 5-HT2A receptor may be involved in vascular smooth muscle
      contraction, coronary artery spasms, platelet aggregation and thrombus formation.
      5-HT2A receptor blockade might protect from ischemic heart disease by decreasing
      platelet aggregation and myocardium hypertrophy. Long-term follow-up studies are
      needed to clearly establish the long-term contribution of the various
      antipsychotic drugs to ischemic heart disease, and to explore our hypothesis that
      5-HT2A receptor blockade may be protective for cardiovascular disease.

PMID- 20053539
TI  - The risk of death among adult participants in trials of antipsychotic drugs in
      schizophrenia.
AB  - In this paper we investigate mortality in short-term placebo-controlled trials
      conducted to demonstrate efficacy and safety of atypical antipsychotic drugs for
      the treatment of schizophrenic patients in the acute phase of illness. Arguments
      are provided, why short-term placebo-controlled studies are required. This is an
      integrated analysis of results from randomized placebo-controlled trials
      conducted pre-licensing for risperidone, olanzapine, quetiapine IR, ziprasidone,
      risperidone consta, aripiprazole, paliperidone, and quetiapine XR. Information
      was retrieved from study publications, EPAR, and from the FDA SBA, all in the
      public domain. 7553 patients were randomized in the remaining 23 short-term acute
      phase clinical trials. 2/5738 patients died after having been randomized to an
      active treatment. 5/1815 died in the placebo group. The crude odds-ratio for an
      increased death risk with placebo treatment is 7.92 (95% confidence interval
      (1.45 to 40.87), two sided P=0.0134). Death narratives show: (i) both deaths in
      active treatment groups occurred during randomized treatment period, (ii) two
      deaths in the placebo group of a trial in the elderly were observed in patients
      with severe co-morbidities not usually included in a randomized trial, and (iii)
      two further deaths in the placebo groups occurred 9 and 23 days after the end of
      the randomized treatment period. Under these circumstances the crude odds-ratio
      for an increased risk of death for patient with placebo as compared to active
      treatment is 1.58 (95% confidence interval (0.14-17.45), two sided P=0.71).
      Confidence intervals are generally wide indicating a still limited knowledge
      about a potential increase in mortality with placebo treatment. Unless, however,
      society is willing to take the risk that ineffective drugs are licensed and cause
      undetected harm thereafter, or is willing to restrict licensing to drugs that are
      superior to current treatments, short-term placebo-controlled trials in the acute
      phase of schizophrenia are necessary. Measures are proposed to minimize risks.

PMID- 20053537
TI  - Avoidant personality disorder symptoms in first-degree relatives of schizophrenia
      patients predict performance on neurocognitive measures: the UCLA family study.
AB  - Whether avoidant personality disorder symptoms are related to neurocognitive
      impairments that aggregate in relatives of schizophrenics is unknown. We report
      the relationship between avoidant personality disorder symptoms and
      neurocognitive performance in the first-degree relatives of probands with
      schizophrenia. 367 first-degree relatives of probands with schizophrenia and 245
      relatives of community controls were interviewed for the presence of avoidant
      personality symptoms and symptoms of paranoid and schizotypal personality
      disorders and administered neurocognitive measures. Relationships between
      neurocognitive measures and avoidant symptoms were analyzed using linear mixed
      models. Avoidant dimensional scores predicted performance on the span of
      apprehension (SPAN), 3-7 Continuous Performance Test (3-7 CPT), and Trail Making
      Test (TMT-B) in schizophrenia relatives. These relationships remained significant
      on the SPAN even after adjustment for paranoid or schizotypal dimensional scores
      and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a
      second set of analyses comparing schizophrenia relatives to controls there were
      significant or trending differences in the degree of the relationship between
      avoidant symptoms and each of these neurocognitive measures even after
      adjustments for paranoid and schizotypal dimensional scores. The substantial
      correlation between avoidant and schizotypal symptoms suggests that these
      personality disorders are not independent. Avoidant and in some cases schizotypal
      dimensional scores are significant predictors of variability in these
      neurocognitive measures. In all analyses, higher levels of avoidant symptoms were
      associated with worse performance on the neurocognitive measures in relatives of
      schizophrenia probands. These results support the hypothesis that avoidant
      personality disorder may be a schizophrenia spectrum phenotype.

PMID- 20053540
TI  - Late potentials in the signal-averaged electrocardiogram in schizophrenia
      patients maintained on antipsychotic agents: a preliminary naturalistic study.
AB  - In the present, preliminary, naturalistic study, cardiac ventricular late
      potentials (LPs), were measured in 33 physically healthy schizophrenia patients
      (13 - females and 26 - males, age - 45.5+/-8.8years) maintained on typical and
      atypical antipsychotic agents. These LPs represent delayed ventricular activation
      that might predispose to fatal ventricular arrhythmias and sudden cardiac death
      (SCD) in cardiac patients. Sixteen of the 33 patients ( approximately 48%) were
      found to be positive for LPs (compared to 3.7-6% in the general population). No
      association was found with any of the following: drug type, anti-cholinergic
      burden, daily dose of antipsychotic agents, age, gender, disease duration, QT(c)
      interval and QT dispersion. Further large-scale longitudinal prospective studies
      are warranted to substantiate our findings and to clarify their impact on the
      excess cardiac morbidity and mortality in schizophrenia patients.

PMID- 20053541
TI  - A study of medical intervention in routine breast cancer follow-up.
AB  - AIMS: The incidence and prevalence of breast cancer is increasing, and survival
      rates continue to climb, placing increasing demands on clinic time. In the modern
      health service, the value of routine follow-up has been questioned, as there is a
      very low rate of detection of asymptomatic recurrences in such clinics. The
      National Institute for Health and Clinical Excellence has recommended potential
      discharge after the completion of adjuvant treatment. However, there is more to
      follow-up than the detection of recurrence. This aim of this study was to
      determine the level and type of intervention occurring within a dedicated
      hospital breast cancer follow-up clinic, taking into account recent developments
      in management. We also reviewed the role of community-based breast cancer follow
      up as an alternative setting to the hospital. MATERIALS AND METHODS: All patients
      attending a dedicated breast cancer follow-up clinic within a hospital setting
      under the care of a single oncologist over a 7 month period were prospectively
      studied. Information regarding tumour characteristics, in addition to any form of
      investigation, intervention and trial recruitment, was recorded for 598 patients.
      RESULTS: A breast cancer-relevant intervention was carried out in 50% of
      patients. Forty-seven patients (7.9%) had their breast medication changed, 81
      (13.5%) were investigated for suspected recurrence and 44 (7.4%) were enrolled
      into a clinical trial. Fourteen (2.3%) patients were referred to another
      specialty; in total, 115 (19.2%) further investigations were carried out related
      to the disease or treatment. CONCLUSIONS: A significant number of interventions
      were undertaken from the clinic. A large proportion of these could be co
      ordinated from primary care, if adequate guidelines are in place. However, rapid
      advances in breast cancer management should be considered, and cost-effectiveness
      needs to be studied before making strong recommendations as to where breast
      cancer follow-up is best managed.

PMID- 20053542
TI  - Factors predicting outcome for advanced gastroesophageal cancer in elderly
      patients receiving palliative chemotherapy.
AB  - AIMS: Most patients with advanced gastroesophageal cancer are elderly, but
      current standard regimens have emerged from trials predominantly involving
      patients with a median age <65 years. The aim of this study was to assess the
      factors influencing survival outcome for an elderly gastroesophageal cancer non
      trial population. MATERIALS AND METHODS: We reviewed the case notes of all
      patients in our centre over the age of 65 years who received palliative
      chemotherapy for gastroesophageal cancer over a period of 3.5 years. Patients
      were classified as having received standard, non-standard combination or single
      agent chemotherapy. After an initial univariate analysis, a multivariate analysis
      of the most significant prognostic factors was carried out. RESULTS: In total,
      120 patients were suitable for analysis. The median overall survival for patients
      receiving standard chemotherapy was 8.1 months, non-standard combination 8.3
      months and single-agent fluoropyrimidines 3.9 months. Poor prognosis was
      predicted by two independent factors: poor performance status (hazard ratio
      2.402; 95% confidence interval 1.53-3.77, P<0.001) and the presence of cancer
      symptoms (hazard ratio 2.235; 95% confidence interval 1.32-3.79, P=0.003).
      CONCLUSIONS: An assessment of the performance status and the level of symptoms is
      vital in this vulnerable group of patients. Prospective randomised trials to
      assess the benefit of chemotherapy in elderly patients with gastroesophageal
      cancer are required.

PMID- 20053543
TI  - Development and validation of the Asthma Life Impact Scale (ALIS).
AB  - BACKGROUND: Current asthma patient-reported outcome (PRO) measures focus on
      symptoms and functioning and may not capture the holistic impact of asthma on the
      quality of life of the patient. OBJECTIVE: To develop a PRO measure capturing the
      overall impact of asthma on patient's quality of life. METHODS: Items for the
      Asthma Life Impact Scale (ALIS) were generated from patients with asthma during
      interviews in the UK and focus groups in the US. The ALIS was tested with UK and
      US asthma patients during cognitive debriefing interviews and included in large,
      two-administration, validation studies in the UK and US. RESULTS: Issues raised
      by asthma patients during interviews (n = 39 patients) and focus groups (n = 16
      patients) were included in the draft ALIS. Cognitive debriefing interviews with
      29 UK and US asthma patients showed that the scale was relevant and
      comprehensive. 140 UK and 185 US asthma patients participated in the validation
      study. The analysis showed that the ALIS measures a single construct, namely the
      overall impact of asthma on patients' quality of life. Internal consistency
      (Cronbach's Alpha) was high (UK = 0.94; US = 0.92) as was test-retest reliability
      (UK = 0.93; US = 0.83). Patients reporting worse general health or more severe
      asthma had significantly higher ALIS scores (p < 0.001) (indicating greater
      negative impact of asthma). Correlations with the Asthma Quality of Life
      Questionnaire were moderate to high. CONCLUSIONS: The final 22-item ALIS is
      unidimensional, reliable and valid, and a valuable tool for comprehensively
      assessing the holistic impact of asthma from the patient's perspective.

PMID- 20053544
TI  - Correlation between airflow limitation and airway dimensions assessed by
      multidetector CT in asthma.
AB  - BACKGROUND: Asthma is characterized by variable airflow obstruction and airway
      wall thickening. Multidetector-row computed tomography (MDCT) is useful for the
      evaluation of airway wall structural changes in asthma. The objective of the
      study is to assess the relationship between airflow limitation and airway
      dimensions from the third to fifth generation bronchi in asthma using MDCT.
      METHODS: Thirty-eight subjects with asthma underwent MDCT to measure the airway
      wall area (WA) and luminal area (Ai), WA and Ai corrected by body surface area
      (BSA), up to the fifth generation of the apical bronchus (B1) and the posterior
      basal bronchus (B10) of the right lung. RESULTS: WA/BSA, WA percentage (WA%) and
      Ai/BSA in the fifth generation were significantly correlated with forced
      expiratory volume in 1 s (FEV(1))% predicted. The correlation coefficients
      between WA% and FEV(1)% predicted increased when tracking the airways from the
      third to the fifth generation (r=-0.25, p>0.05; r=-0.40, p<0.01; r=-0.63, p<0.001
      for B1; r=-0.23, p>0.05; r=-0.47, p<0.01; r=-0.69, p<0.001 for B10). At the
      generation 5, WA% was greater and Ai/BSA was smaller in severe asthma than mild
      to-moderate asthma. CONCLUSION: These results suggest that airway flow limitation
      in asthma is closely related to the more distal airways (third to fifth
      generation).

PMID- 20053545
TI  - Effects of leachate accumulation on landfill stability in humid regions of China.
AB  - Leachate levels are important to landfill stability and safety. High leachate or
      water levels often lead to landfill instability, which can cause accidents. Here
      a case study of a landfill located in a humid region of southern China is
      presented. Leachate distribution and quality were systematically analyzed, and
      the effect of leachate level on waste-mass stability was assessed. Boreholes were
      drilled in the field, samples were analyzed in the laboratory, and a simulation
      was performed. In addition, the safety and stability of the landfill was
      evaluated. The leachate level in the landfill was 9-19m, which was higher than
      the top of the dam crest (8-20m). Leachate accounted for more than 1/4 of the
      total landfill storage capacity. The contaminant concentration of the leachate
      samples collected directly from the waste body was very high, with large
      variation among the samples. The mean concentrations of NH(3)-N, BOD, and COD
      from the waste body were 5404, 14,136, and 22,691mg/L, nearly 2.7, 2.4, and 1.8
      times the mean concentrations in the leachate pond, respectively. Three series of
      shear strength parameters were used in a slope stability analysis, and a limit
      equilibrium method was used to calculate the factor of safety (Fs). The analysis
      showed that Fs could be affected by potential anisotropy in the shear strength of
      the waste. The minimum values of Fs corresponding to series I were 1.84 and 1.17
      for units capital I, Ukrainian and II, respectively. The Fs value of unit II was
      significantly lower than the safe design value (1.25). In addition, Fs decreased
      with increase in the normalized height of the leachate level, h/H, where h is the
      height of the leachate mound and H is the maximum thickness of the landfill. If
      the h/H values of units I and II are kept below 50% and 40%, respectively, a safe
      design value of 1.25 for Fs can be guaranteed. Therefore, some measures to
      prevent risk should be considered.

PMID- 20053546
TI  - Neuronal migration mechanisms in development and disease.
AB  - Neuronal migration is a fundamental process that determines the final allocation
      of neurons in the nervous system, establishing the basis for the subsequent
      wiring of neural circuitry. From cell polarization to target identification,
      neuronal migration integrates multiple cellular and molecular events that enable
      neuronal precursors to move across the brain to reach their final destination. In
      this review we summarize novel findings on the key processes that govern the cell
      biology of migrating neurons, describing recent advances in their molecular
      regulation in different migratory pathways of the brain, spinal cord, and
      peripheral nervous system. We will also review how this basic knowledge is
      contributing to a better understanding of the etiology and pathophysiology of
      multiple neurological syndromes in which neuronal migration is disrupted.

PMID- 20053547
TI  - A cellular perspective on conformational disease: the role of genetic background
      and proteostasis networks.
AB  - The inherently error-prone nature of protein biosynthesis and turnover leads to a
      constant flux of destabilized proteins. Genetic mutations in conformational
      disease-associated proteins, as well as exposure to acute and chronic proteotoxic
      stresses, further increase the load of misfolded protein on the proteostasis
      network. During aging, this leads to enhanced instability of the proteome,
      failure to buffer destabilizing genetic mutations or polymorphisms, and cellular
      decline. The combination of cell-type-specific differences in the buffering
      capacity of the proteostasis network and destabilizing polymorphisms in the
      genetic background may account for some of the cell-type specificity observed in
      disease, even when the predominant disease-associated protein is widely
      expressed.

PMID- 20053549
TI  - Structural and mechanistic insights into translation termination.
AB  - Translation termination is mediated by two classes of peptide release factors
      (RFs). Class I RF recognizes the stop codons and triggers the release of the
      polypeptide chain. Class II RF in prokaryotes promotes dissociation of class I
      RFs from the ribosome whereas in eukaryotes it acts cooperatively with class I RF
      to ensure efficient stop codon recognition and fast peptide release. Advances
      have been made in recent years at astonishing pace to determine the high
      resolution crystal structures of both classes of RFs on and off the ribosome.
      Combined with biochemical analyses, these structures provide considerable
      insights into the mechanistic principles of stop codon recognition and peptide
      release.

PMID- 20053548
TI  - Structural insights into RNA interference.
AB  - Virtually all animals and plants utilize small RNA molecules to control protein
      expression during different developmental stages and in response to viral
      infection. Structural and mechanistic studies have begun to illuminate three
      fundamental aspects of these pathways: small RNA biogenesis, formation of RNA
      induced silencing complexes (RISCs), and targeting of complementary mRNAs. Here
      we review exciting recent progress in understanding how regulatory RNAs are
      produced and how they trigger specific destruction of mRNAs during RNA
      interference (RNAi).

PMID- 20053550
TI  - Lead bioaccumulation potential of an aquatic macrophyte Najas indica are related
      to antioxidant system.
AB  - Plants of Najas indica bioaccumulated significantly higher amounts of Pb (3554
      microg g(-1) dw) when, exposed to varying concentrations of Pb(NO(3))(2).This
      also led to increased malondialdehyde (MDA), electrical conductivity (EC) and
      H(2)O(2) content. In response to this, the activities of antioxidant enzymes such
      as superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase
      (GPX), catalase (CAT) and glutathione reductase (GR) were elevated along with the
      induction of various molecular antioxidants including GSH, cysteine, ascorbic
      acid and proline. Further, Pb exposed plants showed significantly increased
      cysteine synthase and glutathione-S-transferase activity. Visible symptoms of
      toxicity were evident at 50 microM after 4d showing chlorosis and fragmentation
      of leaves with mucilaginous discharge. It seems that bioaccumulated Pb is
      efficiently tolerated by Najas plants through activation of antioxidant system
      and thiolic pathways which was evident by the increased biomass up to 10 microM
      Pb. Therefore, it appears that due to metal tolerance characteristics with high
      concentration factor these plants can find use in phytoremediation of aquatic
      system highly contaminated by Pb.

PMID- 20053551
TI  - Microalgae cultivation in a wastewater dominated by carpet mill effluents for
      biofuel applications.
AB  - Industrial and municipal wastewaters are potential resources for production of
      microalgae biofuels. Dalton - the Carpet Capital of the World generates 100-115
      million L of wastewater d(-1). A study was conducted using a wastewater
      containing 85-90% carpet industry effluents with 10-15% municipal sewage, to
      evaluate the feasibility of algal biomass and biodiesel production. Native algal
      strains were isolated from carpet wastewater. Preliminary growth studies
      indicated both fresh water and marine algae showed good growth in wastewaters. A
      consortium of 15 native algal isolates showed >96% nutrient removal in treated
      wastewater. Biomass production potential and lipid content of this consortium
      cultivated in treated wastewater were approximately 9.2-17.8 tons ha(-1) year(-1)
      and 6.82%, respectively. About 63.9% of algal oil obtained from the consortium
      could be converted into biodiesel. However further studies on anaerobic digestion
      and thermochemical liquefaction are required to make this consortium approach
      economically viable for producing algae biofuels.

PMID- 20053552
TI  - Phenol biodegradation in a batch jet loop bioreactor (JLB): kinetics study and pH
      variation.
AB  - Phenol biodegradation in a batch jet loop bioreactor (JLB) using activated sludge
      was investigated. The biodegradation experiments were conducted at different
      phenol concentrations (S(0)) from 50 to 1000 mg/l. The results of the
      biodegradation of phenol by JLB show that a good phenol removal of 100%. The
      biodegradation capacity of the JLB was higher than that of the stirred tank
      reactor reported in literatures. The Haldane equation was adopted in order to
      describe the relation between the specific growth rates (micro) and S(0). Kinetic
      constants of Haldane equation were micro(m) = 0.119 1/h, K(s) = 11.13 mg/l and
      K(i) = 250.88 mg/l. Model equations were simulated using the MATHCAD 7.0
      software's ordinary differential equation solver. Simulations were performed at
      each experiment with different initial phenol concentrations.

PMID- 20053553
TI  - Investigation of increasing organic loading rate in the co-digestion of energy
      crops and cow manure mix.
AB  - The increase of the organic loading rate from 4.45 to 7.78 g-VS/l-d in a one
      stage, pilot biogas plant was investigated. The experiment was conducted using a
      co-digestion of cow manure and crop silage mix. The test was divided in three
      subsequent phases with different feeding ratios. The benefits of optimizing the
      proportion of crops and loading rate in co-digestion were shown by the fact that
      during feeding with 70% VS of crop in the feedstock, up to 109% higher specific
      methane yield was obtained than during the start up phase (only manure). It was
      also found that further increasing the proportion of crop silage up (to 80%) led
      to a process breakdown with a decrease of methane proportion down to 48%. On the
      basis of the present results, it could be possible to obtain an electricity
      production equal to 15 kwh per 1 t/d. At the end of the monitoring biogas yield
      was equal to 237 and 249l-CH(4)/kg-VS in the first two phases, and to 61.6l
      CH(4)/kg-VS in the third one that led to a process breakdown. The result of this
      study show, that most agricultural biogas plant have a great potential for a
      significant capacity increase and technology improvement.

PMID- 20053554
TI  - Isolation and quantification of cadmium removal mechanisms in batch reactors
      inoculated by sulphate reducing bacteria: biosorption versus bioprecipitation.
AB  - Biosorbing properties of sulphate reducing bacteria were tested to distinguish
      the amount of cadmium removed by bioprecipitation from that bound onto biomass
      surface (biosorption). Experimental results of cadmium abatement in batch growth
      tests (bioprecipitation tests) were then compared with metabolism-independent
      binding properties of SRB cell wall surface (biosorption tests performed with
      dead biomass). Experimental results showed that SRB inoculum removed 59 + or - 5%
      of sulphates in 21 days even in presence of cadmium (0-36 mmol L(-1)), while non
      monotonous kinetic effects were observed for increasing Cd concentrations.
      Comparison between bioprecipitation and biosorption tests denoted a significant
      contribution of biosorption (77%) in total Cd removal (0.40 + or - 0.01 mmol g(
      1)). Characterisation of bacterial acid-base surface properties by potentiometric
      titrations and mechanistic modelling denoted that carboxylic, phosphate and amino
      groups of cell wall are the main responsible of metal removal by biosorption
      mechanism.

PMID- 20053555
TI  - Production and characterization of methyl ester sophorolipids with 22-carbon
      fatty acids.
AB  - In this study, various fatty acids of 18 and 22 carbons were used as substrates
      to produce sophorolipids in Candida bombicola ATCC 22214. Methyl esterification
      of erucic acid and C22-enriched rapeseed oil generated mainly acidic
      sophorolipids with different degrees of saturation in the fatty acid chain, which
      was demonstrated by structural analysis using HPLC, LC-MS and NMR spectroscopy.
      Regardless of methyl esterification, the rapeseed oil served as the best
      substrate for high production of sophorolipids among the tested. Methyl
      esterification also had no noticeable effect on the interfacial properties of
      sophorolipids. However, 22 carbons introduced in the fatty acid chain increased
      the hydrophobicity of sophorolipids, and therefore improved surface-active
      properties and biodegradability.

PMID- 20053556
TI  - Extraction of pectins with different degrees of esterification from mulberry
      branch bark.
AB  - Pectins were extracted from mulberry branch bark, a byproduct of the sericulture
      industry. A single-factor experiment was used to optimize the production
      conditions. Under optimal conditions, the galacturonic acid yields from bark with
      and without epidermis were 61.73 + or - 1.39% and 35.12 + or - 0.24%,
      respectively. The extracted pectins mainly consisted of galacturonic acid with a
      trace amount of neutral sugars, and the total galacturonic acid content in the
      pectins extracted from the bark without epidermis reached 85.46 + or - 2.76%.
      Pectins extracted from bark without epidermis had a higher degree of
      esterification (71.13 + or - 1.67%) than those extracted from bark with epidermis
      (24.27 + or - 2.89%). Pectin solution from bark without epidermis showed higher
      apparent viscosity, suggesting its higher gelation ability. Thus, the mulberry
      branch bark is a potential source of pectin with different degrees of
      esterification.

PMID- 20053557
TI  - Bacteriological characterization of wastewater samples obtained from a primary
      treatment system on a small scale swine farm.
AB  - This study was carried out in order to quantify enteric bacteria and identify the
      presence of Salmonella spp., Escherichiacoli, Clostridiumperfringens and
      Erysipelothixrhusiopathiae in the liquid fraction of excreta generated from a
      small scale swine farm by means of a primary treatment system, consisting of the
      separation of solids and the sedimentation of liquids. Samples were collected at
      the following stages of the treatment: collection basin (CB), liquid obtained
      from a solids separator (SLF) and liquid from the sedimentation basin (SB). In
      each sample, enteric bacteria (cfu/g wet weight) and E. coli were quantified,
      Salmonella spp. was isolated and typified, and C. perfringens, and E.
      rhusiopathiae were isolated. No significant differences (p>0.05) were found in
      the enteric bacteria and E. coli population levels at any treatment stage.
      S.choleraesuis was found in 20% of CB samples analyzed, 40% of SLF samples and
      30% of SB samples. C. perfringens was isolated from SLF and SB. E. rhusiopathiae
      was not isolated (below the minimum detection limit). Results suggest that
      primary treatment does not reduce the amount of enteric bacteria, or eliminate
      Salmonella spp., E. coli and C. perfringens. Therefore, it is necessary to apply
      additional treatments to allow safe use of the liquid obtained in the farm.

PMID- 20053558
TI  - Structural diversity of nucleoside phosphonic acids as a key factor in the
      discovery of potent inhibitors of rat T-cell lymphoma thymidine phosphorylase.
AB  - Structurally diverse, sugar-modified, thymine-containing nucleoside phosphonic
      acids were evaluated for their ability to inhibit thymidine phosphorylase (TP, EC
      2.4.2.4) purified from spontaneous T-cell lymphomas of an inbred Sprague-Dawley
      rat strain. From a large set of tested compounds, among them a number of
      pyrrolidine-based derivatives, 10 nucleotide analogues with IC(50) values below 1
      microM were selected. Out of them, four compounds strongly inhibited the enzyme
      with IC(50) values lying in a range of 11-45 nM. These most potent compounds
      might be bi-substrate analogues.

PMID- 20053559
TI  - Design, synthesis, and evaluation of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5
      a]pyrimidines as novel PDE-4 inhibitors.
AB  - Described herein is design, synthesis, and biological evaluation of novel series
      of 2-aryl-7-(3',4'-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as
      inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for
      the treatment of asthma and COPD. For this purpose, structure optimization was
      conducted with the aid of structure-based drug design using the known X-ray
      crystallography. Also, biological effects of these compounds on the target enzyme
      were evaluated by using in vitro assays, leading to the potent and selective PDE
      4 inhibitor (IC(50)<10nM).

PMID- 20053560
TI  - Discovery of biaryl inhibitors of H+/K+ ATPase.
AB  - We report the identification of a novel biaryl template for H(+)/K(+) ATPase
      inhibition. Evaluation of critical SAR features within the biaryl imidazole
      framework and the use of pharmacophore modelling against known imidazopyridine
      and azaindole templates suggested that the geometry of the molecule is key to
      achieving activity. Herein we present our work optimising the potency of the
      molecule through modifications and substitutions to each of the ring systems. In
      particular sub-micromolar potency is achieved with (4b) presumably through a
      proposed intramolecular hydrogen bond that ensures the required imidazole basic
      centre is appropriately located.

PMID- 20053561
TI  - Potent transglutaminase inhibitors, aryl beta-aminoethyl ketones.
AB  - Aryl beta-aminoethyl ketones were discovered as potent inhibitors of tissue
      transglutaminase. Heteroaryl-like thiophene groups and N-benzyl N-t-butyl
      aminoethyl group are critical to the strong inhibitory activity of aryl beta
      aminoethyl ketones.

PMID- 20053562
TI  - Predictive screening model for potential vector-mediated transport of cationic
      substrates at the blood-brain barrier choline transporter.
AB  - A set of semi-rigid cyclic and acyclic bis-quaternary ammonium analogs, which
      were part of a drug discovery program aimed at identifying antagonists at
      neuronal nicotinic acetylcholine receptors, were investigated to determine
      structural requirements for affinity at the blood-brain barrier choline
      transporter (BBB CHT). This transporter may have utility as a drug delivery
      vector for cationic molecules to access the central nervous system. In the
      current study, a virtual screening model was developed to aid in rational drug
      design/ADME of cationic nicotinic antagonists as BBB CHT ligands. Four 3D-QSAR
      comparative molecular field analysis (CoMFA) models were built which could
      predict the BBB CHT affinity for a test set with an r(2) <0.5 and cross-validated
      q(2) of 0.60, suggesting good predictive capability for these models. These
      models will allow the rapid in silico screening of binding affinity at the BBB
      CHT of both known nicotinic receptor antagonists and virtual compound libraries
      with the goal of informing the design of brain bioavailable quaternary ammonium
      analogs that are high affinity selective nicotinic receptor antagonists.

PMID- 20053563
TI  - Identification of potential and selective collagenase, gelatinase inhibitors from
      Crataegus pinnatifida.
AB  - Four oligomeric procyanidins were isolated from the MeOH extracts of the leaves
      of Crataegus pinnatifida (Rosaceae). Investigation of collagenase and gelatinase
      inhibitory natural components afforded four oligomeric procyanidins. Of these, 2
      and 3 exhibited collagenase inhibitory activity (IC(50)) at a concentration of
      less than 1 microM, and 3 showed gelatinases A and B inhibitory activity (IC(50))
      at 0.4 and 2.3 microM, respectively.

PMID- 20053564
TI  - Novel semisynthetic spin-labeled derivatives of podophyllotoxin with cytotoxic
      and antioxidative activity.
AB  - A series of novel spin-labeled podophyllotoxin derivatives were synthesized by
      reacting the corresponding N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxy
      carbonyl)-amino acids with 4beta-amino-4'-demethylepipodophyllotoxin. The
      synthesized derivatives 12a-g were evaluated for the partition coefficients,
      cytotoxicities in vitro against three tumor cell lines (A-549, HL-60, and RPMI
      8226) and antioxidative activities in tissues of SD rats by the TBA method. The
      vast majority of target compounds have shown superior or comparable activities
      against A-549, HL-60, and RPMI-8226 compared to VP-16, and they have shown more
      significant antioxidative activities and superior water solubility than VP-16.

PMID- 20053565
TI  - Synthesis and antimicrobial activity of 2-fluorophenyl-4,6-disubstituted
      [1,3,5]triazines.
AB  - A series of 2-fluorophenyl-4,6-disubstituted [1,3,5]triazines (1) and (2) were
      synthesized and evaluated for their antimicrobial activity against three
      representative gram-positive bacteria and two fungi. The structure-activity
      relationship (SAR) demonstrates that the 3- or 4-fluorophenyl component attached
      directly to the triazine ring was essential for activity. Of these compounds, 14,
      15, and 25 demonstrated significant activity against all selected organisms
      compared to control. These compounds were generally nontoxic and may prove useful
      as antimicrobial agents.

PMID- 20053566
TI  - Obstacle stepping in children: task acquisition and performance.
AB  - The aim of this study was to investigate the locomotor capacity of children
      during the performance of different lower extremity tasks with increasing
      difficulty. Two subject groups of children (aged 6-8 and 9-12 years) and adult
      controls performed several motor tasks from the Zurich Neuromotor Assessment
      (ZNA) test, as well as a unilateral and bilateral obstacle stepping test during
      treadmill walking. Performance of ZNA items, changes in foot clearance, and
      obstacle hits were assessed. Correlations between children's age, ZNA and
      obstacle measures were calculated. Performance of all motor tasks improved with
      increasing age. All three groups improved foot clearance during unilateral
      obstacle stepping, while the younger children achieved a poorer performance
      level. During bilateral obstacle stepping, only the adult controls and the 9-12
      years old children's group further improved foot clearance, while no further
      improvement occurred in the 6-8 years old children's group. A relationship
      between items of ZNA and bilateral obstacle stepping was found. It is concluded
      that children in the mid-childhood range are able to significantly improve
      performance of a high-precision locomotor task. However, children below 9 years
      of age have a poorer motor performance compared to older children and adults that
      becomes more pronounced with increasing complexity of the task. Finally, ZNA
      tests can improve the prediction of complex adaptive locomotor behaviour compared
      to calendar age alone.

PMID- 20053567
TI  - Site-specific labeling of 'second generation' annexin V with 99mTc(CO)3 for
      improved imaging of apoptosis in vivo.
AB  - In this study 'second generation' AnxV was specifically labeled with (99m)Tc in
      three different ways outside the binding region of the protein to obtain an
      improved target-to-background activity ratio. The compounds were tested in vitro
      and in vivo in normal mice and in a model of hepatic apoptosis (anti-Fas mAb).
      The apoptosis binding was most prominent for the HIS-tagged 'second generation'
      AnxV labeled with (99m)Tc(CO)(3) in comparison to (99m)Tc-HYNIC-cys-AnxV and
      (99m)Tc(CO)(3)-DTPA-cys-AnxV.

PMID- 20053568
TI  - Elemental analysis of silver coins by PIXE technique.
AB  - Elemental analysis of nine Indian silver coins during British rule was carried
      out by proton induced X-ray emission spectroscopy. Eight elements, namely Cr, Fe,
      Ni, Cu, Zn, As, Ag, and Pb were determined in the present study. Ag and Cu were
      found to be the major elements, Zn was the only minor element and all other
      elements are present at the trace level. The variation of the elemental
      concentration may be due to the use of different ores for making coins.

PMID- 20053569
TI  - Cardiotrophin-1 and TNF-alpha circulating levels at rest and during
      cardiopulmonary exercise test in athletes and healthy individuals.
AB  - BACKGROUND: There is a growing body of evidence that physical training exerts its
      potential benefits on the individual health status by modulating the immune
      system and the whole body metabolism. A better knowledge of the physiologic
      immune response to exercise may help to understand the benefits of physical
      exercise in healthy individuals and elite athletes. AIMS: This study aims to
      analyse cardiotrophin-1 (CT-1) and Tumor Necrosis Factor-alpha (TNF-alpha) plasma
      levels at rest and during exercise in elite athletes and healthy controls.
      METHODS: We studied 20 triathletes (TA) and 20 matched controls (CG). Chambers
      dimensions, left ventricular mass and left ventricular mass index were analysed
      by echocardiography. VO2 peak and VE/VCO2 were calculated by metabolic stress
      test. Blood samples were collected before the exercise session, at the exercise
      peak, and after the end of exercise. ELISA assays were used to measure CT-1 and
      TNF-alpha plasma levels. RESULTS: Among TA and CG, no significant differences
      were found for CT-1 (0.25+/-0.14 vs 0.20+/-0.14 fm/l; p=0.29) and TNF-alpha
      (10.8+/-2.7 vs 9.7+/-4.0 pm/l; p=0.29) basal levels. In the TA, plasma levels of
      CT-1 were significantly different at rest and during exercise (basal 0.25+/-0.13
      pm/l; peak 1.07+/-1.5 pm/l; post-exercise 0.67+/-0.77 pm/l; p=0.04). Conversely,
      no significant differences were found between basal, peak and post-exercise
      plasma values of TNF-alpha (basal 10.8+/-2.7 pm/l; peak 11.7+/-2.1 pm/l; post
      exercise 11.4+/-2.5 pm/l; p=0.78) in TA. CONCLUSIONS: This study gives novel
      insights on the behavior of inflammatory cytokines during physical exercise in
      athletes and healthy individuals.

PMID- 20053570
TI  - Nuclear acoustic resonance in fluids using piezoelectric nanoparticles.
AB  - The influence of acoustic radiation in the form of ultrasound (US) on the nuclear
      magnetic resonance (NMR) signal of liquids in the presence of piezo- and
      ferroelectric nanoparticles was investigated. The NMR resonances of 1H and 23Na
      were influenced by US with a frequency of omega(US)=18.26 MHz. For hydrogen, US
      with a frequency omega(US)=omega(0) was used where omega(0) is the Larmor
      frequency of 18.26 MHz. For sodium, US with a frequency omega(US)=2omega(0,Na)
      was used with omega(0,Na)=9.13 MHz. A detailed description of nanoparticle
      properties and sample preparation is given. The influence of US on the spin
      lattice relaxation time T(1) was determined with an inversion recovery sequence
      for different concentrations of PZT. An elongation of T(1) of (1)H by 1.7% at a
      PZT concentration of 0.05% and an elongation of T(1) of (23)Na by 3% at a PZT
      concentration of 0.04% was observed. The elongation scales with the concentration
      of the PZT. An possible explanation of the effect of elongation is discussed.

PMID- 20053571
TI  - Spectral estimation of irregularly sampled exponentially decaying signals with
      applications to RF spectroscopy.
AB  - The problem of estimating the spectral content of exponentially decaying signals
      from a set of irregularly sampled data is of considerable interest in several
      applications, for example in various forms of radio frequency spectroscopy. In
      this paper, we propose a new nonparametric iterative adaptive approach that
      provides a solution to this estimation problem. As opposed to commonly used
      methods in the field, the damping coefficient, or linewidth, is explicitly
      modeled, which allows for an improved estimation performance. Numerical examples
      using both simulated data and data from NQR experiments illustrate the benefits
      of the proposed estimator as compared to currently available nonparametric
      methods.

PMID- 20053572
TI  - Estimating quadrupole couplings of amide deuterons in proteins from direct
      measurements of 2H spin relaxation rates.
AB  - The measurements of longitudinal and transverse 2H spin relaxation rates of
      backbone amide deuterons (D(N)) in the [U-13C,15N]-labeled protein ubiquitin show
      that the utility of amide deuterons as probes of backbone order in proteins is
      compromised by substantial variability of D(N) quadrupolar coupling constants
      (QCC) from one amide site to another. However, using the dynamics parameters of
      15N-2H bond vectors evaluated from 15N relaxation data, site-specific QCC values
      can be estimated directly from D(N)R1 and R2 rates providing useful information
      on hydrogen bonding in proteins. In agreement with previous indirect scalar
      relaxation-based measurements, the D(N) QCC values estimated directly from R1 and
      R2 2H relaxation rates correlate with the inverse cube of the X-ray structure
      derived hydrogen bond distances in ubiquitin: QCC=(232+/-2.3)+(118+/-17)
      summation operator(i)(cosalpha)r(i)(-3) where r is the inter-nuclear hydrogen
      bond distance in angstroms, and alpha is the N-D....O(i) angle.

PMID- 20053573
TI  - A practical implementation of cross-spectrum in protein backbone resonance
      assignment.
AB  - The concept of cross-spectrum is applied in protein NMR spectroscopy to assist in
      the backbone sequential resonance assignment. Cross-spectrum analysis is used
      routinely to reveal correlations in frequency domains as a means to reveal common
      features contained in multiple time series. Here the cross-spectrum between
      related NMR spectra, for example HNCO and HN(CA)CO, can be calculated with point
      by-point multiplications along their common C' carbon axis. In the resulting
      higher order cross-spectrum, an enhanced correlation signal occurs at every
      common i-1 carbon frequency allowing the amide proton H(N) (and nitrogen N)
      resonances from residues i and i-1 to be identified. The cross-spectrum approach
      is demonstrated using 2D spectra H(N)CO, H(NCA)CO, H(NCO)CACB, and H(N)CACB
      measured on a 15N/13C double-labeled Ubiquitin sample. These 2D spectra are used
      to calculate two pseudo-3D cross-spectra, H(i)-H(i)(-1)-C'(i)(-1) and H(i)-H(i)(
      1)-CA(i)(-1)CB(i)(-1). We show using this approach, backbone resonances of H, C',
      CA, and CB can be fully assigned without ambiguity. The cross-spectrum principle
      is expected to offer an easy, practical, and more quantitative approach for
      heteronuclear backbone resonance assignment.

PMID- 20053574
TI  - Intermolecular single-quantum coherence sequences for high-resolution NMR spectra
      in inhomogeneous fields.
AB  - A new pulse sequence based on intermolecular single-quantum coherences (iSQCs) is
      proposed to obtain high-resolution NMR spectroscopy in inhomogeneous magnetic
      fields via fast 2D acquisition. Taking the intrinsic properties of iSQCs, the
      sequence is time-efficient with a narrow spectral width in the indirect
      dimension. It can recover useful information of chemical shifts, relative peak
      areas, J coupling constants, and multiplet patterns even when the field
      inhomogeneity is severe enough to erase almost all spectroscopic information.
      Moreover, good solvent suppression efficiency can be achieved by this sequence
      even with imperfect radio-frequency pulse flip angles. Spatially localized iSQC
      spectroscopy was performed on a sample packed with pig brain tissue and cucumber
      to show the feasibility of the sequence in in vivo magnetic resonance
      spectroscopy (MRS). This sequence may provide a promising way for the
      applications on in vivo and in situ high-resolution NMR spectroscopy.

PMID- 20053575
TI  - Structural stabilization of a rigid beta-sheet cluster of fucosylated proteinase
      inhibitor PMPC (Pars intercerebralis major peptide C) against thermal
      denaturation: An unfolding molecular dynamics simulation study.
AB  - Unfolding behavior of glycosylated- and unglycosylated proteinase inhibitor Pars
      intercerebralis major peptide C (PMPC) at 350 K were traced with molecular
      dynamics simulations using the CHARMM program. The fucosylated PMPC (FPMPC)
      possesses a nearly identical protein structure with PMPC, differing only by the
      presence of a single fucose residue linked to Thr9 in the PMPC. Attachment of a
      monomeric fucose residue to the Thr9 in PMPC resulted in a change of the
      denaturing process of FPMPC. Simulations showed that the unfolding of PMPC
      involved significant weakening of non-local interactions whereas fucosylation led
      FPMPC to preserve the non-local interactions, even in its denatured form. Even in
      simulations over 16 ns at 350 K, FPMPC remained relatively stable in a less
      denatured conformation. However, the conformation of PMPC transformed to a fully
      unfolded state within 5 ns in the simulation at 350 K. This difference was due to
      the formation of fucose-mediated hydrogen bonds and non-local contacts by the
      attached fucose residue of FPMPC. In the case of FPMPC, fucosyl residue was
      involved in maintaining a rigid beta-sheet cluster through interaction with the
      hydrogen bond network. These high-temperature unfolding MD simulations provide a
      theoretical basis for a previous experimental work in which FPMPC showed stable
      unfolding thermodynamics compared to unfucosylated PMPC, suggesting that single
      fucosylation induces conformational stabilization of PMPC by tertiary contacts.

PMID- 20053576
TI  - Very low penetrance of Leber's hereditary optic neuropathy in five Han Chinese
      families carrying the ND1 G3460A mutation.
AB  - We report here the clinical, genetic, and molecular characterization of five Han
      Chinese families with Leber's hereditary optic neuropathy (LHON). Strikingly,
      there were very low penetrances of visual impairment in these Chinese families,
      ranging from 4.2% to 22.2%, with an average of 10.2%. In particular, only 7 (4
      males/3 females) of 106 matrilineal relatives in these families exhibited the
      variable severity and age-at-onset in visual dysfunction. The age-at-onset for
      visual impairment in matrilineal relatives in these families, varied from 20 to
      25 years, with an average of 21.8 years old. Molecular analysis of mitochondrial
      genomes identified the homoplasmic ND1 G3460A mutation and distinct sets of
      variants, belonging to the Asian haplogroups B5b, C4a1, D5, F1, and R9,
      respectively. This suggests that the G3640A mutation occurred sporadically and
      multiplied through evolution of the mtDNA in China. However, there was the
      absence of known secondary LHON-associated mtDNA mutations in these Chinese
      families. Very low penetrance of visual loss in these five Chinese pedigrees
      strongly indicated that the G3640A mutation was itself insufficient to develop
      the optic neuropathy. The absence of secondary LHON mtDNA mutations suggest that
      these mtDNA haplogroup-specific variants may not play an important role in the
      phenotypic expression of the G3640A mutation in those Chinese families with low
      penetrance of vision loss. However, nuclear modifier genes, epigenetic and
      environmental factors appear to be modifier factors for the phenotypic
      manifestation of the G3640A mutation in these Chinese families.

PMID- 20053577
TI  - Staphylococcus intermedius--rare pathogen of acute meningitis.
AB  - We report the first case of acute meningitis caused by a rare, atypical pathogen.
      An 11-month-old infant was admitted to hospital with clinical symptoms typical of
      acute meningitis. Cerebrospinal fluid analysis revealed an elevated neutrophil
      cell count and high proteins. Microbiological examination of the fluid confirmed
      an atypical cause of meningitis--Staphylococcus intermedius. Antibiotic therapy
      with cefotaxime was successful and the child made a full recovery.

PMID- 20053578
TI  - Ultrasound assisted synthesis of monoclinic structured spindle BiVO4 particles
      with hollow structure and its photocatalytic property.
AB  - Bismuth vanadate (BiVO(4)) spindle particles with monoclinic scheelite structure
      have been successfully synthesized via a facile sonochemical method. The as
      prepared BiVO(4) photocatalyst exhibited a hollow interior structure constructed
      from the self-assembly of cone shape primary nanocrystals. A possible oriented
      attachment growth mechanism has been proposed based on the results of time
      dependent experiments, which indicates the formation of spindle particles is
      mainly attributed to the phase transformation procedure induced by ultrasound
      irradiation. A series of morphology evolutions of BiVO(4) from compact
      microspheres, to hollow microspheres, and then to spindle particles have been
      arrested in the process of sonochemical treatment. Optical absorption experiments
      revealed the BiVO(4) spindle had strong absorption in the visible light region. A
      much higher photocatalytic activity of these spindle particles was found in
      comparison with the SSR-BiVO(4) material for degradation of rhodamine-B under
      visible light irradiation, which may be ascribed to its special single
      crystalline nanostructure.

PMID- 20053579
TI  - A comparison of a topography-based rigid gas permeable contact lens design with a
      conventionally fitted lens in patients with keratoconus.
AB  - PURPOSE: To determine if a clinically comparable contact lens could be designed
      for patients with keratoconus utilising a corneal topographer and its contact
      lens design software. METHODS: A total of 30 patients with keratoconus were
      recruited for this randomized, double-masked prospective study. Corneal
      topography was performed on each patient using the Orbscan II (Bausch & Lomb, NY,
      USA) topographer. The topographers' Fitscan RGP fitting software was used to
      derive a tri-curve rigid contact lens specification. This was manufactured, and
      then compared by three experienced clinicians with the patients' conventionally
      fitted (habitual) lens. Each aspect of contact lens fitting was graded, and each
      grade was weighted for kappa analysis to determine if there was any significant
      difference between the Fitscan-derived lens and the patients' habitual lens.
      RESULTS: Percentage agreement levels between the two fitting techniques were
      between 74% and 100%. Kappa values varied from below 0 to 0.60, indicating poor
      to moderate agreement. A slight bias towards flatter apical fitting in the
      Fitscan design was found in some cases of advanced keratoconus. There was no
      systematic bias for either fitting technique when comparing visual performance
      and lens comfort. A higher percentage of Fitscan-derived lenses were deemed
      suitable to dispense to patients, either directly or after minor parameter
      modification. CONCLUSION: This study demonstrates that a satisfactory lens design
      for keratoconic patients can be produced utilising a topography-based system,
      when compared to a patients' conventionally fitted lens. The potential advantages
      of this system include simplified lens selection and reduced trial lens usage,
      with a reduction in patient discomfort, clinical chair-time and costs.

PMID- 20053581
TI  - Synthesis, crystal structures and photoluminescence of 7-(N,N'-diethylamino)-3
      phenylcoumarin derivatives.
AB  - Two new coumarin derivatives, 7-(N,N'-diethylamino)-3-(4-hydroxyphenyl)-coumarin
      and 7-(N,N'-diethylamino)-3-(4-bromophenyl)-coumarin, were synthesized
      successfully. Their structures were verified by single crystal X-ray
      crystallography. The UV-vis absorption and fluorescence of the compounds were
      discussed. The compounds exhibit strong blue emission under ultraviolet light
      excitation. The molecular structures, the lowest energy transitions and the UV
      vis spectra of 7-(N,N'-diethylamino)-3-(4-hydroxyphenyl)-coumarin and 7-(N,N'
      diethylamino)-3-(4-bromophenyl)-coumarin have been studied with density
      functional theory (DFT) and time-dependent density functional theory (TD-DFT) at
      B3LYP/6-31G(d) level.

PMID- 20053580
TI  - Anaplasma phagocytophilum and Ehrlichia chaffeensis type IV secretion and Ank
      proteins.
AB  - The obligatory intracellular bacterial pathogens Anaplasma and Ehrlichia infect
      leukocytes by hijacking host-cell components and processes. The type IV secretion
      system is up-regulated during infection. Among type IV secretion candidate
      substrates, an ankyrin repeat protein of Anaplasma phagocytophilum, AnkA, is
      delivered into the host cytoplasm via a complex that includes VirD4. AnkA is
      highly tyrosine phosphorylated and binds to the Abl interactor 1, SHP-1, and
      nuclear DNA fragments. Ehrlichia chaffeensis AnkA was recently reported to be
      translocated into host-cell nucleus. The recent discovery of several ankyrin
      repeat proteins secreted via the type IV secretion system of different
      intracellular bacteria suggests that a common strategy evolved to subvert host
      cell functions.

PMID- 20053582
TI  - USB-based Personal Health Records: an analysis of features and functionality.
AB  - PURPOSE: To determine the features of commercially available USB-based Personal
      Health Records (PHR) devices, and compare the commercial state of the art to
      recommendations made by certification committees. METHODS: Thirteen USB-based
      PHRs were identified and analyzed based on data elements used and features
      provided. Marketing techniques used by the companies were also explored. RESULTS:
      Eight of the thirteen PHRs contained all seven clinical data elements (problems,
      procedures, medications, providers, allergies, labs, immunizations), three were
      missing a single element and the remaining two lacked two elements. In the
      features analysis no single PHR contained all eight features (export data, import
      data, images, summary print out, emergency entry, teaching material available for
      problem, username and password supported, Mac-compatible), but two of the devices
      had seven of the eight features. Finally, scare tactics were used in marketing
      all but two of the PHR devices. CONCLUSION: While PHRs are very important in the
      health care field, at the present time, USB-based PHRs currently on the market
      appear to have deficiencies. Tethered or web-based PHRs may be a better option
      for consumers at present.

PMID- 20053583
TI  - Transmission of betapapillomaviruses between domestic partners in an Australian
      community.
AB  - BACKGROUND: Betapapillomaviruses may be associated with the development of
      cutaneous squamous cell carcinoma but little is known about their transmission.
      One suggestion is that they are transmitted through close skin contact.
      OBJECTIVES: To test this hypothesis we assessed whether co-habiting opposite-sex
      couples were more or less likely to share betaPV types than each member of the
      couple and an age-matched, opposite-sex control. STUDY DESIGN: Betapapillomavirus
      was measured in eyebrow hairs of 57 couples and 114 age- and sex-matched
      controls. We compared the proportion of partners who shared at least one betaPV
      type with the proportion of control partnerships sharing a betaPV type. We
      further subdivided those who shared at least one type into those who shared only
      one and those who shared more than one. We tested the significance of differences
      in these proportions using Chi-squared tests. A case-wise concordance index was
      used to calculate the overall concordance of the partners and the control
      pairings. RESULTS: At least one betaPV type was shared by 39% of the co-habiting
      couples and 26% of the control pairs (p=0.10). When restricted to all people with
      at least one virus infection (26 couples) 74% of the partners and 46% of the
      control pairs shared at least one type (p=0.02). The case-wise concordance index
      for partners was 0.28 (95% CI 0.21-0.35) and for the matched control pairs 0.16
      (95% CI 0.12-0.20) (p<0.001). CONCLUSIONS: Our results support the hypothesis
      that skin-to-skin contact is the primary means of betapapillomavirus
      transmission.

PMID- 20053584
TI  - The role of cats and dogs in asthma and allergy--a systematic review.
AB  - Studies have reported contradictory effects of cat and dog exposure on allergy,
      resulting in inconsistent recommendations on animal avoidance. We conducted a
      systematic review of observational studies published in English from 2000 to
      January 2009. It shows in this review that the reported exposure-response
      relationships are contradictory. A total of 17 and 13 birth cohort studies on cat
      and dog exposure, respectively, are included in the review. Most of the birth
      cohort studies found that cat or dog exposure in early life had no effect on the
      development of asthma or wheezing symptoms and dog exposure during infancy was
      found to protect children from developing sensitization against aeroallergens. A
      total of 7 and 6 prospective studies in school-age children or adults on cat and
      dog exposure, respectively, are included in this review and most of these studies
      suggested an inverse association between cat exposure and asthma and wheezing
      symptoms. As for cross-sectional studies, 26 and 21 studies on cat and dog
      exposure, respectively, are included in this review, which cover a broad range of
      age groups and geographical areas, and reported inconsistent results. The
      evidence summarised in this systematic review needs to be interpreted with
      caution, the inconsistent study results may be due to study design, exposure
      assessment, and avoidance measure. The exposure-response relationships may also
      alter in geographical areas where the community prevalence of cats and dogs are
      significantly different. However, as the evidence of the effects of pet keeping
      on subsequent development of asthma or allergic diseases presented in this review
      are not overwhelmingly strong, the decision of whether to keep a cat or a dog in
      the family should be based on arguments other than the concern of developing
      asthma and allergy.

PMID- 20053585
TI  - Long-term outcome of severe hypospadias.
AB  - OBJECTIVE: To evaluate, from the patient's point of view, long-term urinary and
      sexual outcome of surgery for severe hypospadias. PATIENTS AND METHOD: Patients
      treated for severe posterior hypospadias during childhood and now aged 20-35
      years were included. Outcome was evaluated using the Hypospadias Objective
      Scoring Evaluation and our own quality of life questionnaire. RESULTS: Of 48
      patients, 13 were lost to follow up. The questionnaire was thus sent to 35
      patients of whom 27 agreed to answer (77% response rate). Fifteen presented
      proximal and 12 scrotal hypospadias. Average age at surgery was 3.3 years and the
      children underwent an average of 3.7 procedures. There were 40% early
      complications, and 59% late complications, including 33% fistulae and 26%
      stenosis. At present, 70% of patients have an apical meatus, 82% have a straight
      penis, 37% present difficulty initiating voiding, and one patient has a
      persistent fistula; 74% say their penis looks abnormal, either because of the
      absence of foreskin, penis size or scarring. Sexual and global satisfaction
      rates, determined using a visual analogue scale, are respectively 68% and 63%.
      Satisfaction is statistically correlated to the presence of early complications
      or stenosis, but not fistula. It decreases if the patient thinks his penis is not
      normal, even if the anatomical result is good. CONCLUSION: Urinary and sexual
      outcome is good for most patients though the results are variable. Satisfaction
      seems more affected by subjective feelings than the anatomical result.

PMID- 20053586
TI  - Interleukin-4 inhibits an early phase in the HIV-1 life cycle in the human
      colorectal cell line HT-29.
AB  - Intestinal epithelial cells are continuously in contact with the gut-associated
      lymphoid tissues (GALT). Gastrointestinal infection by viruses, bacteria and
      parasites or the presence of an inflammatory bowel disease may influence the GALT
      cytokine network. However, the effect of the different cytokines on
      susceptibility of human intestinal epithelial cells to HIV-1 infection remains
      undefined. We demonstrate here that IL-4 inhibits infection with reporter HIV-1
      viruses pseudotyped with NDK-Env without affecting integrated proviral DNA.
      Furthermore, IL-4 also inhibits, in a dose-dependent manner, infection of HT-29
      cells with HIV-1-based AMLV, HTLV-I and VSV-G pseudotypes. A fusion assay showed
      that this event is not affected by IL-4, thus suggesting that a post-fusion step
      is affected. A reduction in the completion of DNA retrotranscription indicates
      that IL-4 may affect this step, or any prior event. Altogether our data indicate
      that IL-4 is negatively affecting an early post-fusion step in the HIV-1
      replication cycle in HT-29 cells.

PMID- 20053587
TI  - Nerve injuries after neuraxial anaesthesia and their medicolegal implications.
AB  - Serious and permanent neurologic complications in the obstetric population are
      rare. Most neurologic complications following childbirth are intrinsic obstetric
      palsies. The most common intrinsic obstetric palsy is lateral femoral neuropathy.
      Palsies of the femoral, obturator, sciatic, common peroneal nerves and
      lumbosacral plexus have also been reported. Meticulous technique during neuraxial
      anaesthesia will decrease the risk of injury secondary to neuraxial procedures.
      Direct trauma to the spinal cord and spinal nerves may occur during neuraxial
      anaesthesia. Sterile technique should be employed during neuraxial procedures and
      precautions should be taken to ensure that the proper drug/concentration is being
      injected. Postpartum complaints should be addressed promptly. For infection and
      space-occupying lesions of the neuraxial canal, prompt diagnosis and treatment
      are essential to prevent permanent injury or death. Survey studies have
      demonstrated that women want to be told of the risks of neuraxial procedures,
      even when the incidence is rare.

PMID- 20053588
TI  - Knowledge, attitudes, and practice toward epilepsy (KAPE): a survey of Chinese
      and Vietnamese adults in the United States.
AB  - We conducted, in four languages, the first national cross-sectional survey of the
      knowledge, attitudes, and practice with respect to epilepsy of Chinese- and
      Vietnamese-American adults. We used a convenience sampling method to recruit 2831
      adults in seven states. Eighty-four percent had heard or read of epilepsy and 58%
      had seen a seizure, whereas only 34% knew someone with epilepsy. Forty-two
      percent would object to their children marrying a person with epilepsy, and 43%
      would not knowingly hire someone with epilepsy. We examined bivariate
      associations for questions of knowledge, attitudes, and practice with age,
      gender, ethnicity, nativity, language, and education. chi(2) analyses showed
      differences in knowledge of and attitudes toward epilepsy by age group, gender,
      ethnicity, and education. Although misconceptions and negative views about
      epilepsy are held by Chinese and Vietnamese populations living in the United
      States, our results show noteworthy differences in attitudes and practice in
      relation to previous studies in Asian countries.

PMID- 20053589
TI  - Dietary salt enhances angiotensin-II-induced superoxide formation in the rostral
      ventrolateral medulla.
AB  - We investigated the association of dietary salt and angiotensin-II infusion on
      hypertension and superoxide formation in the RVLM. Male Wistar rats were
      subcutaneously infused with Ang-II (150ng/kg/min) or saline (0.9% NaCl) for
      14days. In addition, rats had free access to drinking water containing 0.4% or
      2.0% NaCl. On the 15th day, rats that received Ang-II+0.4% NaCl exhibited higher
      levels of baseline arterial blood pressure than rats that received saline+0.4%
      NaCl (118+/-5mm Hg vs 98+/-4mm Hg, n=9, P<0.05). Rats that received Ang-II+2%
      NaCl had a significantly greater hypertension compared to Ang-II+0.4% NaCl (165+/
      7mm Hg vs 118+/-5mm Hg, n=10, P<0.05). On the other hand, rats treated with
      saline+2% NaCl or saline+0.4% NaCl did not become hypertensive (96+/-5mm Hg, n=8
      and 98+/-4mm Hg, n=7, respectively). Furthermore, administration of hexamethonium
      (30mg/kg i.v.) evoked larger decreases in mean arterial pressure in rats treated
      with Ang-II+2% NaCl and rats treated with Ang-II+0.4% NaCl (-100+/-5 Deltamm Hg
      and -72+/-10 Deltamm Hg, P<0.05). The magnitude of superoxide formation measured
      by the dihydroethidium technique in the RVLM was greater in the RVLM of rats
      treated with Ang-II+2% NaCl (123+/-10 Delta%, P<0.05%), than with Ang-II+0.4%
      (67+/-9 Delta%) and saline+2% NaCl (5+/-3 Delta%,). The findings indicate that
      dietary salt potentiates Ang-II-derived superoxide formation in the RVLM,
      resulting in a more severe hypertension. We suggest that this effect could be
      mediated by an increase in inputs within the forebrain-PVN-RVLM axis.

PMID- 20053590
TI  - The effects of celiac ganglionectomy on sympathetic innervation to the splanchnic
      organs in the rat.
AB  - The sympathetic nervous system is important in blood pressure regulation, and
      regionally-specific increases in sympathetic nerve activity occur during the
      development of hypertension. Sympathetic neurons innervating the splanchnic
      organs may be especially critical, because sympathetic activity to the splanchnic
      region is increased early in hypertension development. The celiac ganglionic
      plexus contains the majority of the sympathetic neurons innervating the
      splanchnic organs and tissues. Celiac ganglionectomy (CGX) involves surgical
      removal of the celiac ganglionic plexus, and has been used to study the roles of
      the splanchnic sympathetic innervation in cardiovascular regulation. In the
      current study we characterized the short-term (two-week) and long-term (five-week
      and ten-week) effects of CGX in rats on splanchnic sympathetic nerve structure
      and function. In the short-term, norepinephrine concentrations in whole
      splanchnic organs and mesenteric arteries and veins were significantly decreased
      by CGX. Immunohistochemistry and glyoxylic acid staining showed an almost
      complete loss of the typical sympathetic innervation of mesenteric arteries and
      veins. Additionally, CGRP-containing sensory nerves largely disappeared.
      Constrictor responses of mesenteric arteries and veins to sympathetic nerve
      stimulation were abolished by CGX. However, the effects of CGX were time
      dependent, since significant regeneration of sympathetic nerves in some organs
      was observed 5weeks after surgery. The inferior mesenteric ganglion had minimal
      impact on this reinnervation process. In vivo studies showed that CGX
      significantly lowers resting blood pressure in normal Sprague-Dawley rats.
      Therefore, CGX is an effective means to impair sympathetic input to the
      splanchnic organs, but the effect of the procedure is not permanent.

PMID- 20053591
TI  - Explore various co-substrates for simultaneous electricity generation and Congo
      red degradation in air-cathode single-chamber microbial fuel cell.
AB  - Microbial fuel cell (MFC) holds a great promise to harvest electricity directly
      from a wide range of ready degradable organic matters and enhance degradation of
      some recalcitrant contaminants. Glucose, acetate sodium and ethanol were
      separately examined as co-substrates for simultaneous bioelectricity generation
      and Congo red degradation in a proton exchange membrane (PEM) air-cathode single
      chamber MFC. The batch test results showed that more than 98% decolorization at
      the dye concentration of 300 mg/L were achieved within 36 h for all tested co
      substrates during electricity generation. The decolorization rate was different
      with the co-substrates used. The fastest decolorization rate was achieved with
      glucose followed by ethanol and sodium acetate. Accumulated intermediates were
      observed during Congo red degradation which was demonstrated by UV-Visible
      spectra and high performance liquid chromatography (HPLC). Electricity generation
      was sustained and not significantly affected by the Congo red degradation.
      Glucose, acetate sodium and ethanol produced maximum power densities of 103
      mW/m(2), 85.9 mW/m(2) and 63.2 mW/m(2), respectively, and the maximum voltage
      output decreased by only 7% to 15%. Our results demonstrated the feasibility of
      using various co-substrates for simultaneous decolorization of Congo red and
      bioelectricity generation in the MFC and showed that glucose was the preferred co
      substrate.

PMID- 20053592
TI  - [Update on photoprotection in children].
AB  - Children are one of the population groups in which the photo-protection must be
      maximised. Firstly, because they take part in outdoor activities more often than
      adults. Secondly, because the principal risk factor for all types of skin cancer
      is ultraviolet radiation, and in particular, cumulative exposure during
      childhood. Hence, decreasing exposure to ultraviolet radiation in childhood has
      the potential to significantly lower the incidence of most forms of skin cancer.
      Photoprotection includes behavioural measures to protect the skin from sun
      exposure, e.g. sun protective clothes, hats, sunglasses, and sunscreens. It is
      necessary to provide information on aphotoprotection to parents, and, above all,
      to children, using educational campaigns to increase knowledge of photoprotection
      to help change attitudes towards sun exposure. Dermatologists and Paediatricians
      play a essential role in this educational work. In this article we review the
      latest information regarding paediatric sun protection, the new sunscreens, and
      the recent sun protection educational programs.

PMID- 20053593
TI  - The 'v-intermammary dart'--a simple method for avoiding central dog ears in
      reduction mammaplasty.

PMID- 20053594
TI  - 'I only give advice if I am asked': examining the grandmother's potential to
      influence infant feeding decisions and parenting practices of new mothers.
AB  - BACKGROUND: Australia has high breastfeeding initiation rates however, at 3 and 6
      months exclusive breastfeeding rates fall below global recommendations. Research
      suggests significant others in a woman's life can influence infant feeding
      decisions and practices but how and why they do so needs investigation. RESEARCH
      QUESTION: This study explored grandmothers' perceptions of their role in
      supporting new families and examined the potential for grandmothers to influence
      infant feeding decisions and parenting practices of new mothers in an area of
      Sydney, Australia, with low breastfeeding maintenance rates. PARTICIPANTS AND
      METHOD: A qualitative, descriptive study was conducted in South Western Sydney,
      Australia. Eleven grandmothers participated in one to one interviews and three of
      these also participated in a group discussion. RESULTS: Analysis revealed three
      themes: 'Presence'; 'Position'; and 'Power versus Preservation' which provide
      insight into the complexity of the grandmother-new mother relationship and
      describe the potential influence that grandmothers may have on infant feeding and
      parenting. DISCUSSION AND CONCLUSION: The findings highlight challenges and
      dilemmas faced by grandmothers in their supportive role for the new mother in her
      breastfeeding and early parenting experience and the difficulties grandmothers
      face in balancing potential risks and rewards in their interactions with the new
      family.

PMID- 20053596
TI  - [Outbreak of indigenous dengue in the Buenos Aires Metropolitan Area. Experience
      of the F. J. Muniz Hospital].
AB  - As a consequence of the dengue epidemic in the Bolivian Republic and the northern
      provinces of Argentina, an outbreak of indigenous dengue occurred for the first
      time in the Buenos Aires Metropolitan Area. Since January 2009 we assisted
      imported dengue cases coming from epidemic regions; later, around the end of
      March, and until middle autumn, indigenous cases appeared. The major
      concentration of these indigenous cases was in the west area of Buenos Aires City
      and in the neighboring localities 3 de Febrero and La Matanza. There were several
      factors that made the local transmission possible: a high vector density, people
      traveling from epidemic areas and clustering in the geographical zone where the
      indigenous epidemic occurred, during a period with high medium temperatures,
      entering 95% of the imported cases during the first days of the viremia. Of the
      nine patients with alarming signs for the development of severe dengue, seven
      were indigenous cases with no previous history of dengue infections. We report
      the clinical and epidemiological findings, and we analyze the factors which
      regulated the transmission.

PMID- 20053595
TI  - Genetic effects on toxic and essential elements in humans: arsenic, cadmium,
      copper, lead, mercury, selenium, and zinc in erythrocytes.
AB  - BACKGROUND AND OBJECTIVES: An excess of toxic trace elements or a deficiency of
      essential ones has been implicated in many common diseases or public health
      problems, but little is known about causes of variation between people living
      within similar environments. We estimated effects of personal and socioeconomic
      characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu),
      mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested
      for genetic effects using data from twin pairs. METHODS: We used blood samples
      from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30-92
      years of age) and determined element concentrations in erythrocytes by
      inductively coupled plasma-mass spectrometry. We assessed associations between
      element concentrations and personal and socioeconomic characteristics, as well as
      the sources of genetic and environmental variation and covariation in element
      concentrations. We evaluated the chromosomal locations of genes affecting these
      characteristics by linkage analysis in 501 dizygotic twin pairs. RESULTS:
      Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial
      correlations, concentrations of As and Hg due mainly to common genetic effects.
      Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near
      SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and
      suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se
      (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family
      11 (proton-coupled divalent metal ion transporters)]}. CONCLUSIONS: Although
      environmental exposure is a precondition for accumulation of toxic elements,
      individual characteristics and genetic factors are also important. Identification
      of the contributory genetic polymorphisms will improve our understanding of trace
      and toxic element uptake and distribution mechanisms.

PMID- 20053597
TI  - [Hereditary angioedema. Family history and clinical manifestations in 58
      patients].
AB  - Hereditary angioedema (HAE) is a rare autosomal dominant disease, characterized
      by episodes of edema typically involving the skin, gastrointestinal tract and
      larynx. We here describe the epidemiologic and clinical characteristic of a
      series of 58 patients with diagnosis of HAE, 53 (91%) type I and 5 (9%) type II.
      The mean age at first symptom was 10.8 +/- 9.5 years and the mean age at
      diagnosis was 25.8 +/- 16.2 years old, with a diagnosis delay of 15.3 +/- 14.3
      years. The mean number of attacks in the previous 6 months was 7.4 +/- 7.6 range
      0 to 40. Fifty four (93%) had cutaneous attacks, 50 (86%) abdominal attacks, 24
      (41%) laryngeal attacks and 24 (41%) combined cutaneous and abdominal attacks.
      Twenty seven (46.5%) patients never received preventive treatments and 17 (29%)
      received danazol in different doses for different periods of time. During the
      attacks, 15 (26%) patients were treated with C1 inhibitor at least once, 7 (12%)
      with fresh frozen plasma and 40 (69%) received only supportive treatment. Stress
      and trauma were identified as attacks triggers. Six (10%) patients were first
      mutation and 52 (90%) had HAE ancestors. We reconstructed 20 kindred, identifying
      205 individuals at risk of inheriting the disease, 109 (53 %) of them had signs
      or laboratory diagnosis of HAE. The total number of identified HAE individuals
      was 145, 19 (13%) died with asphyxia. So, shortening of diagnosis delay and
      appropriate treatment of HAE are a challenge to be fulfilled.

PMID- 20053598
TI  - [Medical students' attitudes regarding professional practice].
AB  - Although the choice to study medicine implies some knowledge of the current
      working situation of practitioners, medical students' expectations regarding
      their future professional practice have been rarely investigated in Argentina.
      The aim of this work was to collect data about the expectations of senior medical
      students regarding their future professional practice. One hundred and twenty
      five senior medical students were surveyed between September and December 2008.
      By using an anonymous survey, information regarding the expectations about their
      future professional practice was collected. The survey was answered by 82.4%
      (103/125) of the students and 98.0% (101/103) expressed their desire to enter a
      residence programme. Regarding specialty, pediatrics and psychiatry were the most
      chosen by women (27% vs. 8%, p=0.029 and 27% vs. 3%, p=0.004), and orthopedic
      surgery was the predominant choice in men (18% vs. 2%, p=0.019). Median of
      expected income at 5 years post graduation was $ 4.000 (minimum: $1,500, maximum:
      $10.000), at 10 years $7.000 (minimum: $3.000, maximum: $ 20.000) and at 20 years
      $10.000 (minimum: $3.000, maximum: $30,000), according to money value adjusted to
      December 2008 ($3.0 = US$ 1.0). In conclusion, chosen specialties seem to be
      dependent on the increasing number of female students, the expected income would
      exceed the current remuneration of physicians. Noteworthy finding out the
      students' willingness to be involved in teaching and the less interest in
      research.

PMID- 20053599
TI  - [Treatment with bisphosphonates and atypical fractures].
AB  - In the last twenty five years aminobisphosphonates have became the drugs of
      choice for the treatment of osteoporosis. They strongly inhibit osteoclastic bone
      resorption and reduce the incidence of new fractures in patients with established
      osteoporosis, but their long half-life and their chronic effects on bone
      physiology are a matter of concern. Theoretically a harmful consequence of a
      prolonged inhibition of bone remodeling could be the microdamage accumulation,
      and paradoxically the occurrence of new and atypical fractures. Until now, few
      cases of these unusual fractures have been reported in the international
      literature. All these patients shared some common characteristics, apart from the
      chronic use of bisphosphonates for the treatment of osteoporosis. The more
      frequent is the atypical location of the fractures. Since the majority happened
      in one or both femoral shafts, others bones such as sacrum, ischium, ribs and
      pubic rami could be affected. The fractures were atraumatic or caused by minimal
      trauma and, in some cases, it was preceded by a prodromal pain in the affected
      area. All cases had biochemical or histomorphometric evidence of low bone
      turnover. The aim of this paper is to report three new cases of patients that
      fulfill with the diagnostic criteria of this new entity, two of them with femoral
      shaft fractures and the remainder with a pelvis one.

PMID- 20053600
TI  - Lymphocyte P-glycoprotein variability in healthy individuals.
AB  - The aim of the present work was to describe the distribution of lymphocyte P
      glycoprotein activity on a population of healthy individuals, taking also into
      account sex and age. P-glycoprotein activity in lymphocytes was measured by the
      Rhodamine 123 efflux assay using flow cytometry, in the presence and absence of
      verapamil, a P-glycoprotein inhibitor. We obtained a range of P-glycoprotein
      activity from 1.04 to 3.79. The distribution of the activity in the population
      studied was better described by a bimodal model, according with the Kolmogorov
      Smirnov test. The frequency adjusted to the following equation: F = 0.70 N (2.11;
      0.43) + 0.30 N(3.29; 0.26), in which 0.70 and 0.30 represented the proportion of
      each group, and 0.43 and 0.26 were the standard deviations of the activity of
      each group, respectively. The study of the relationship between subjects' age and
      P-glycoprotein activity showed no statistical significance. When healthy
      volunteers were separated according to sex, similar distributions were observed,
      although for men an increase in proportion of higher P-glycoprotein function
      group was observed. The variability observed in the population studied was
      important, with some volunteers with very scarce activity and some with a
      fourfold higher activity. Characterization of P-glycoprotein functionality in the
      population represents a useful contribution to the beginning of pharmacological
      treatments that consider its effect on pharmacokinetics and pharmacodynamics of
      individualized patients.

PMID- 20053601
TI  - [Distribution of vectors of visceral leishmaniasis in the Province of Corrientes,
      2008].
AB  - Visceral leishmaniasis (VL) is a relevant parasitic disease in public health,
      produced by Leishmania infantum chagasi. Since the urbanization and emergence in
      Southern Brazil and Paraguay, the vector Lutzomyia longipalpis in Formosa, 2004,
      and the first human visceral leishmaniasis case in Misiones, 2006, have been
      reported in Argentina. Due to the reports of canine VL, a search of the vector in
      the Province of Corrientes, contiguous to Misiones, was performed during December
      2008. Standarized trapping detected 376 Lu. longipalpis in Ituzaingo, Virasoro,
      Santo Tome, Garruchos, Riachuelo, Corrientes and Monte Caseros localities. The
      risk of autochtonous vectorial transmission was then confirmed in the Province of
      Corrientes. The distribution of vectors in populated urban areas, with intense
      transit of canine reservoirs from localities with high transmission, and the
      existence of infected reservoirs, also implies epidemic risk.

PMID- 20053602
TI  - [Health literacy in patients attending a University Hospital].
AB  - Low level of health literacy is associated with poor communication between
      patients and clinicians and with increased hospitalization rates, less frequent
      screening for cancer, poor control of diabetes, and disproportionately high rates
      of disease and mortality. Despite the importance of health literacy in medicine,
      there is no information about its prevalence in Latin America. The aim of this
      study was to assess the prevalence of inadequate health literacy in a random
      sample of patients, at a University Hospital where a descriptive study was
      performed during 2007. Health literacy was assessed through the Short Assessment
      of Health Literacy for Spanish-speaking Adults. Participants were randomly
      selected from the ambulatory clinic and from the medical inpatient ward during
      2007. There were a total of 2345 patients potentially eligible during the time of
      the study, 234 were approached after random selection and 229 patients were
      interviewed (98% response); 54.6% of respondents were women and 62% were
      recruited from the ambulatory clinic. The respondents had a median age of 56
      years. The prevalence of inadequate health literacy was 30.1% (69 patients).
      Patients with <or= 7 years of formal education had more risk of having inadequate
      health literacy compared with those with > 12 years of education OR = 45.1 (IC
      9.6-211.6). We found a high prevalence of inadequate health literacy, being
      strongly associated with the level of formal education. It is important that
      health care providers know the implications of health literacy and its
      consequences.

PMID- 20053603
TI  - [Vitamin D deficit in adult women living in Buenos Aires City].
AB  - Vitamin D deficiency is a common cause of morbidity. We prospectively studied 224
      consecutive female patients in order to evaluate the prevalence of vitamin D
      deficiency and to assess the utility of various clinical and biochemical markers
      in predicting the deficiency. All of them were outpatients, 30 years old or
      older, and were evaluated from October 2006 through March 2008. Levels of 25 OH
      vitamin D > 30 ng/ml were considered sufficient. Mild deficiency was considered
      between 20 and 30 ng/ml and severe deficiency < 20 ng/ml. The mean age was 58 +/-
      12.9 years; 77% were menopausal. Twenty nine percent of the patients had mild
      deficit and 26.8% had severe deficit of the vitamin. Severe deficit was
      associated with increasing age (62 vs. 56 years, p = 0.003), absence of sun
      exposure (25.82 ng/ml vs. 31.7 ng/ml, p < 0.005), obesity (70 vs. 61 kg, p <
      0.05), absence of physical activity (27.8 ng/ml vs. 31.04 ng/ml, p = 0.0007) and
      slightly low levels of serum calcium (9.26 mg/dl vs. 9.51 mg/dl, p 0.01). We did
      not find any association between smokers and non-smokers patients, levels of
      serum phosphorus, creatinine and TSH. Vitamin D deficiency is a common disorder.
      It correlates with older age, absence of physical activity, sun exposure, obesity
      and slightly low levels of serum calcium. Improving diagnosis of this condition
      may enable us to improve the management of this disease.

PMID- 20053604
TI  - [Wegener's granulomatosis and tuberculosis. A bad combination].
AB  - Wegener's disease is a vasculitis of small and medium-sized vessels associated
      with anti-neutrophil cytoplasm antibodies (ANCA). Within their target organs the
      lungs are involved in 85% of cases. Many entities are part of the differential
      diagnosis, including pulmonary tuberculosis. We present the case of a 54 years
      old man, diagnosed as Wegener's disease in 1996 which begins in August 2007 with
      cough, hemoptysis, progressive dyspnea on effort and serial sputum positive for
      AFB and then starts TB treatment. Subsequent bronchoalveolar fluids resulted
      negative for AFB. The patient evolved with impaired renal function, palpable
      purpura and positive anti-neutrophil cytoplasm antibodies cytoplasmic pattern (c
      ANCA), interpreted as Wegener's disease relapse. He started hemodialysis and
      immunosuppressive therapy and tuberculosis treatment was stopped. One month after
      discharge was readmitted with a similar picture with serial sputum positive for
      AFB.

PMID- 20053605
TI  - [Diagnosis of a human rabies case in Jujuy, 2008].
AB  - On July 22, 2008, a previously healthy 8 years old boy from Jujuy, Argentina,
      died of encephalitis later confirmed as rabies. Diagnosis was made on the basis
      rabies-specific antibodies presence in a serum sample and it was confirmed by
      detection of the viral antigens in brain necropsy using the immunofluorescent
      test. Antigenic characterization identified dog as source of infection. Molecular
      analysis recognized the same genetic variant circulating in Jujuy since 2003.
      This report presents the patient's clinical course and the epidemiologic
      investigation that revealed a dog bite 60 days before the illness onset and the
      lack of rabies treatment.

PMID- 20053606
TI  - [Geographic expansion of hantavirus pulmonary syndrome in Argentina. The
      southernest case report].
AB  - Since 1995 more than 1000 cases of hantavirus pulmonary syndrome (HPS) were
      reported in Argentina, a severe disease and often fatal to humans. Most cases
      were associated with Andes virus (AND) that caused few events of person-to-person
      transmission. Several lineages of pathogenic AND viruses have been described,
      including AND South, hosted by the rodent Oligoryzomys longicaudatus which
      affects the Patagonian region of Argentina and Chile. We studied the clinical and
      epidemiological characteristics of a HPS case. The objective was to describe the
      clinical presentation of the case, its epidemiology, the likely site of
      infection, the viral variant implicated and its relationship with the closest
      reported cases. We carried out the clinical follow up, serological and molecular
      diagnosis and the epidemiological research, including a rodent reservoir study.
      The clinical presentation of the case was the classical and moderate, caused by
      AND South virus. Its viral nucleotide sequence was compared with cases from
      Southern Argentina and Chile. This case was found to be the most Southern (48
      degrees 46' 1.2'' S; 70 degrees 15' O) case reported and involved a new
      Argentinean province.

PMID- 20053607
TI  - [A rare blood group: p phenotype].
AB  - A rare blood group is usually defined as the absence of a high prevalence antigen
      or the absence of several antigens within a single blood group system. These
      individuals may develop clinically significant red cell antibodies to the high
      incidence red cell antigens they lack. A 33-year-old alloimmunized woman was
      referred to our center at the 12th week of her third pregnancy for evaluation and
      follow up. The laboratory work-up grouped her as belonging to "p" phenotype,
      associated with difficulties to find compatible blood for transfusion and a high
      incidence of recurrent miscarriage. At 36 weeks, a baby girl was born by induced
      labor due to fetal suffering. With a negative direct antiglobulin test but a
      positive elution test, she was in the neonatology ward for one week receiving
      luminotherapy. Homozygosity for a missense mutation at position 752 (c.752C > T)
      in the A4GALT gene was found to be responsible for the p phenotype. This mutation
      changes a proline to a leucine at codon 251 of the 4-?-galactosyltransferase.
      Recently, due to an imminent chirurgical intervention and the impossibility to
      have compatible blood available for transfusion, an autologous donation plan was
      designed to satisfy probable demand. This case showed the need for blood bank
      facilities capable to respond satisfactorily to these situations in Argentina.
      This would facilitate the storage of cryopreserved blood from individuals with
      rare blood groups for homologous use or to develop rare blood donors programs.

PMID- 20053608
TI  - [Catheter- associated bacteremia caused by Ochrobactrum anthropi].
AB  - Ochrobactrum anthropi is a non-glucose fermentative, aerobic gram-negative
      bacillus, formerly known as Achromobacter sp or CDC group Vd. It has been
      isolated from the environment and from infections in usually immunocompromised
      human beings. The documented infections frequently involved catheter related
      bacteremia whereas endophthalmitis, urinary infections, meningitis, endocarditis,
      hepatic abscess, osteochondritis, pelvic abscess and pancreatic abscess were
      rarely involved. Here it is presented the case of a male patient aged 69 years
      with sustained hypotension, four day febrile syndrome, chill, lavish perspiration
      and sensorium deterioration. He had type 2 diabetes and antecedent of
      cerebrovascular accident. A double-lumen dialysis catheter was present due to
      chronic renal insufficiency. An episode of catheter-related bloodstream infection
      was documented by using Bact-Alert Blood Culture System and Differential-Time-to
      Positivity Method for central venous catheter versus peripheral blood cultures
      (>120 min). Once removed, it was confirmed through Maki semi quantitative
      technique (>15 FCU). The microorganism was identified by API 20NE and Vitek 1 as
      Ochrobactrum anthropi.

PMID- 20053609
TI  - [Intralobular pulmonary sequestration].

PMID- 20053610
TI  - [Leukoencephalopathy due to radiotherapy].

PMID- 20053611
TI  - [Acute respiratory distress syndrome in an adult due to influenza A(H1N1)].

PMID- 20053612
TI  - [Pulmonary-renal syndrome].
AB  - The pulmonary-renal syndrome is defined as a combination of diffuse alveolar
      hemorrhage and glomerulonephritis. The coexistence of these two clinical
      conditions is due to diseases with different pathogenic mechanisms. Primary
      systemic vasculitis and Goodpasture syndrome are the most frequent etiologies.
      Systemic lupus erythematosus, connective tissue diseases, negative anti
      neutrophil cytoplasmic antibody vasculitis and those secondary to drugs are far
      less common causes. An early diagnosis based on clinical, radiologic, laboratory
      and histologic criteria enables early treatment, thus diminishing its high
      morbidity-mortality rate. Therapy is based on high doses of corticosteroids,
      immunosuppressants, tumor necrosis factor inhibitors and plasmapheresis.

PMID- 20053613
TI  - In what clinical settings should Cushing's syndrome be suspected?
AB  - Despite its low frequency, endogenous Cushing's syndrome is not an exceptional
      clinical entity. A growing number of cases are currently derived to specialized
      centers suggesting an increasing knowledge of the clinical features of
      hypercortisolism by specialists of diverse branches of clinical medicine.
      Clinical signs derive from an exaggeration of the physiological actions of
      cortisol inducing protein breakdown, hyperglycemia, fat mobilization,
      dyslipidemia, hydrosaline retention, immunosuppression and increased
      susceptibility to infection. Despite its low specificity, symptoms such as
      unexplained development of central obesity, mood changes, fatigue, weakness,
      myopathy, easy bruisability, red striae, arterial hypertension, diabetes and
      hyperlipidemia, are suggestive of the diagnosis. From an epidemiological point of
      view, Cushing's syndrome is to be suspected and consequently searched for among
      patients with uncontrolled high blood pressure or diabetes mellitus, metabolic
      syndrome, polycystic ovarian syndrome, osteoporosis, depression or adrenal
      incidentaloma. True Cushing's syndrome has to be differentiated from pseudo
      syndromes. Most sensitive physical signs for discriminating Cushing's syndrome
      from pseudo-Cushing states are the presence of supraclavicular fat pads,
      myopathy, thin skin and easy bruising. The recognition of the clinical
      manifestations of Cushing's syndrome and of the sub-populations at risk of
      contracting the disease should be improved through medical education at the
      medical school and at postgraduate levels. Clinical detection of Cushing's
      syndrome must be performed mainly by non-endocrinologists, yet its etiological
      diagnosis and therapeutic management is to be carried out in highly experienced
      and specialized centers, to ensure the best results in the treatment of this
      really challenging endocrine disturbance.

PMID- 20053614
TI  - [Where chromosomes end. Nobel Prize of Physiology or Medicine 2009].

PMID- 20053615
TI  - [The art and politics of science. Bernardo A. Houssay and Harold Varmus].

PMID- 20053616
TI  - [Good practice in clinical investigation].

PMID- 20053617
TI  - [Should Wegener's disease retain its name?].

PMID- 20053618
TI  - High-sensitivity C-reactive protein and total antioxidant status in patients with
      essential arterial hypertension and dyslipidemia.
AB  - PURPOSE: To assess low-grade, systemic inflammation and antioxidant status as
      additional factors contributing to pathophysiology of essential arterial
      hypertension (HTN) and compare them with traditional risk factors, like abnormal
      lipids profile, considering their potential diagnostic usefulness. MATERIAL AND
      METHODS: Serum high-sensitivity C-reactive protein (hs-CRP) concentrations and
      total antioxidant status (TAS) were measured in 143 subjects - 71 patients with
      diagnosed HTN and in 72 healthy controls. RESULTS: In hypertensive patients, as
      compared to healthy control group, the median hs-CRP concentration was higher
      (2.0 mg/L, 25%; 75% quartile range: 0.1; 27.1 vs 0.4 mg/L, 25%; 75% quartile
      range: 0.0; 4.6, respectively, p<0.001) and TAS concentration lower (1.4 mmol/L,
      25%; 75% quartile range: 1.0; 2.1 vs 1.5 mmol/L, 25%; 75% quartile range: 0.5;
      1.8, respectively, p=0.048). Hypertensives had higher low-density lipoprotein
      cholesterol concentration (LDL-C) as well as triglycerides concentration (TG) and
      lower high-density lipoprotein cholesterol concentration (HDL-C). Higher
      diagnostic sensitivity was found for hs-CRP (87%) and for TAS (89%). According to
      the global linear regression analysis, age, gender, hs-CRP, TAS and HDL-C were
      the only parameters influencing the occurrence of HTN. ROC analysis identified hs
      CRP, HDL-C and TG as statistically significant to diagnose HTN (0.839; 0.816 and
      0.855, respectively). Moreover, in ROC analysis there were no differences in hs
      CRP and TAS in females and males. CONCLUSIONS: These results indicate that low
      grade, systemic inflammation measured by hs-CRP as well as antioxidant status
      assessed by TAS, in the presence of traditional risk factors, are significant
      factors contributing to pathophysiology and diagnosis of essential arterial
      hypertension.

PMID- 20053619
TI  - A and B preaxial polydactyly with syndactyly of feet and hands in the same person
      -a case report.
AB  - Preaxial polydactyly of the hand is more common than postaxial polydactyly and
      postaxial polydactyly of the foot is more common than preaxial in white patients.
      Syndactyly is commonly regarded as next in frequency among the congenital hand
      deformities. Preaxial polydactyly of the feet and hands and polydactyly type A
      and B with syndactyly in the same individual is a rare condition. In this work we
      present this rare disorder in male infant. The physical and X-ray examinations
      showed preaxial polydactyly type A of both hands and A and B polydactyly with
      syndactyly of feet.

PMID- 20053620
TI  - Irritant vocal cord dysfunction and occupational bronchial asthma: differential
      diagnosis in a health care worker.
AB  - OBJECTIVES: Vocal cord dysfunction (VCD) is an uncommon respiratory disease
      characterized by the paradoxical adduction of vocal cords during inspiration,
      that may mimic bronchial asthma. The pathogenesis of VCD has not been clearly
      defined but it is possible to recognize non-psychologic and psychologic causes.
      The majority of patients are female but, interestingly, a high incidence of VCD
      has been documented in health care workers. A misdiagnosis with asthma leads to
      hospitalisation, unnecessary use of systemic steroids with related adverse
      effects, and sometimes tracheostomy and intubation. In a subset of VCD patients,
      the disease can be attributed to occupational or environmental exposure to
      inhaled irritants. MATERIALS AND METHODS: We report the case of a 45-year-old
      woman, working as a nurse, who complained of wheezing, cough, dyspnoea related to
      inhalation of irritating agents (isopropylic alcohol, formaldehyde, peracetic
      acid). She underwent chest radiography, pulmonary function assessment both in the
      presence and in the absence of symptoms, bronchial provocation with methacholine
      and bronchodilation test with salbutamol to recognize asthma's features, allergy
      evaluation by skin prick tests and patch tests and video-laryngoscopy. RESULTS:
      VCD diagnosis was made on the basis of video-laryngoscopy, that visualized the
      paradoxical motion of the vocal cords during symptoms, in the absence of other
      pathologic processes. CONCLUSIONS: This case fulfils the proposed criteria for
      the diagnosis of irritant VCD (IVCD). This is the first report of VCD onset
      following exposure to several irritants: formaldehyde, glutaraldehyde, sopropylic
      alcohol, peracetic acid-hydrogen peroxide mixture. These substances are used as
      cleaning and antiseptic agents in healthcare settings and some ones can also be
      found in many indoor environments. A correct diagnosis is important both to give
      the appropriate treatment and for medical legal implications.

PMID- 20053621
TI  - Work-related respiratory symptoms in bird zoo keepers--questionnaire data.
AB  - OBJECTIVES: To investigate the risk factors for the development of airway
      diseases from occupational exposure to birds' allergens among Polish zoo garden
      keepers caring for birds. METHODS: Two hundred workers responded to the
      questionnaire including the history of work-related symptoms, job
      characteristics, description of occupational exposure, information on smoking
      habit, contact with birds and animals at home and family history of allergic
      diseases. RESULTS: General work-related symptoms were reported by 58 subjects
      (29%), whereas work-related respiratory symptoms were found in 40 workers (20%).
      The multivariate logistic regression analysis confirmed the significant role of
      positive family history of atopy and occupational contact with parrots either in
      the development of work-related symptoms or work-related respiratory allergic
      symptoms. CONCLUSIONS: The findings may confirm that work-related respiratory
      symptoms are an important health problem among zoo bird keepers in Poland.

PMID- 20053622
TI  - Polish mother and child cohort study--defining the problem, the aim of the study
      and methodological assumption.
AB  - OBJECTIVES: Exposures during prenatal period have implications for pregnancy
      outcome as well as for children's health, morbidity and mortality. Prospective
      cohort study design allows for the identification of exposures that may influence
      pregnancy outcome and children's health, verification of such exposures by
      biomarker measurements and notification of any changes in exposure level.
      MATERIALS AND METHODS: Polish Mother and Child Cohort Study (REPRO_PL) is
      multicenter prospective cohort study conducted in 8 different regions of Poland.
      The final cohort is intended to comprise 1300 mother-child pairs to be recruited
      within 4-year period (2007-2011). The recruitment and all scheduled visits are
      conducted in maternity units or clinics in the districts included in the study.
      The women are followed-up 3 times in pregnancy (once in each trimester) and after
      delivery for the notification of pregnancy outcome. During each visit, detailed
      questionnaire and biological samples are collected including saliva, urine, hair,
      maternal blood and cord blood. About 6 weeks postpartum, breast milk from part of
      the women is collected. The study concentrates on the identification and
      evaluation of the effects of prenatal environmental exposure on pregnancy outcome
      and children's health. Specific research hypotheses refer to the role of heavy
      metals, exposure to polycyclic aromatic hydrocarbons (PAHs) and environmental
      tobacco smoke (ETS) in the aetiology of small-for-gestational-age (SGA) and
      preterm delivery (PD). The role of oxidative stress putative mechanism and
      pregnant women nutritional status will be investigated. Based on questionnaire
      data, the impact of occupational exposures and stressful situations will be
      evaluated. RESULTS: The results of the study will become available within the
      next few years and will help to determine levels of child prenatal exposure in
      several areas of Poland and its impact on course and outcome of pregnancy.

PMID- 20053623
TI  - Environmental factors and semen quality.
AB  - OBJECTIVES: An increasing number of reports suggest that chemical and physical
      agents in the environment, introduced and spread by human activity, may affect
      male fertility in humans. This article aims at evaluating the impact of
      environmental exposures (pesticides, phthalates, PCBs, air pollution,
      trihalomethanes (THMs), mobile phones) on semen quality, by reviewing most recent
      published literature. MATERIALS AND METHODS: Epidemiological studies focusing on
      exposure to environmental factors and semen quality for the last ten years were
      identified by a search of the Pubmed, Medline, Ebsco, Agricola and Toxnet
      literature bases. RESULTS: The results from the presented studies suggest that
      there are strong and rather consistent indications that some pesticides besides
      DBCP (e.g. DDT/Dichlorodiphenyldichloroethylene [DDE], ethylenedibromide,
      organophosphates) affects sperm count. PCBs are detrimental to sperm motility. In
      case of air pollution, studies suggest a link between ambient air pollutants and
      various semen characteristics. Additional research is needed to corroborate this
      association and to establish the causal agents. Results of few studies on
      subfertile men demonstrate associations between phthalate levels commonly
      experienced by the public and impaired sperm quality (impact on sperm
      concentration, morphology, motility), but the findings have not been corroborated
      in studies of men from the general population. Mobile phones might adversely
      affect the quality of semen by decreasing mostly motility but also the sperm
      counts, viability and morphology. In spite of their consistent results, most of
      the studies are rather small. Association between exposure to THMs and poor semen
      quality was not observed. CONCLUSIONS: Epidemiological studies suggest awareness
      of environmental factors which may affect semen quality. In case both of well
      proven and disputable reproductive and developmental hazards, it is necessary to
      prevent parental exposure to the agents associated with those hazards.

PMID- 20053624
TI  - Pharmacokinetic profile in relation to anaesthesia characteristics after a 5%
      micellar microemulsion of propofol in the horse.
AB  - BACKGROUND: To define the pharmacokinetic profile of propofol 5% microemulsion
      formulation in horses. METHODS: First, propofol was administered as bolus
      injection (2 mg kg(-1)) to six xylazine-sedated horses. Secondly, after sedation
      and bolus injection, propofol was maintained with continuous infusion for 3 h
      [8.1 (sd 3.2) mg kg(-1) h(-1)] to the same six horses. Thirdly, in two horses, a
      commercial propofol was used for comparison. Response to noxious stimulation was
      used to evaluate analgesia. Venous blood samples were obtained to measure
      propofol plasma concentration using liquid chromatography-mass spectrometry
      analysis. The plasma concentrations were related to the anaesthesia
      characteristics to determine the ED(50). RESULTS: The pharmacokinetic profile of
      propofol is best characterized by a non-compartmental model. The mean (confidence
      interval) for area under plasma concentration-time curve, elimination half-life,
      mean residence time, and clearance was 41 min microg ml(-1) (+/-7.7), 44.8 min
      (+/-21.3), 13.7 min (+/-3.2), and 45.8 ml min(-1) kg(-1) (+/-6.5), respectively.
      Linear regression analysis showed a correlation between plasma concentration and
      infusion rate (r(2)=0.47). Most propofol infusion rates did not inhibit the
      response to noxious stimulation and rates above 11.9 mg kg(-1) h(-1) caused
      involuntary muscle contractions. Better recoveries were associated with lower
      propofol plasma concentrations. Propofol plasma concentration frequently
      increased when horses woke from anaesthesia. CONCLUSIONS: Caution is warranted
      when propofol is used for continuous infusion due to variable kinetics, myoclonal
      activity, poor analgesia, and less desirable recovery quality.

PMID- 20053625
TI  - Pandemic (H1N1) 2009 influenza.
AB  - The clinical picture in severe cases of pandemic (H1N1) 2009 influenza is
      markedly different from the disease pattern seen during epidemics of seasonal
      influenza, in that many of those affected were previously healthy young people.
      Current predictions estimate that, during a pandemic wave, 12-30% of the
      population will develop clinical influenza (compared with 5-15% for seasonal
      influenza) with 4% of those patients requiring hospital admissions and one in
      five requiring critical care. This review covers the background, clinical
      presentation, diagnosis, and treatment. The role of immunization and antiviral
      drugs is discussed. Experience from the first wave of pandemic (H1N1) 2009
      influenza suggests that a number of infected patients become critically ill and
      require intensive care admission. These patients rapidly develop severe
      progressive respiratory failure which is often associated with failure of other
      organs, or marked worsening of underlying airways disease. The critical care
      management of these patients and the implications for resources is reviewed.
      Guidance from a range of bodies has been produced in a relatively short period of
      time in response to pandemic (H1N1) 2009 influenza. Disease severity has the
      potential to change, especially if there is virus mutation. Clinicians must be
      prepared for the unexpected and continue to share their experiences to maximize
      patient outcomes.

PMID- 20053626
TI  - Reduced expression of the O-mannosyltransferase 2 (AfPmt2) leads to deficient
      cell wall and abnormal polarity in Aspergillus fumigatus.
AB  - Protein O-mannosyltransferases (PMTs) initiate O-mannosylation of secretory
      proteins, which are of fundamental importance in eukaryotes. The human fungal
      pathogen Aspergillus fumigatus possesses three genes encoding for PMTs, namely,
      Afpmt1, Afpmt2 and Afpmt4. We have previously shown that lack of AfPmt1 leads to
      a temperature-sensitive phenotype featured with severe defects in hyphal growth,
      conidiation, cell wall integrity and morphology at elevated temperatures. In this
      study, a conditional mutant P2 was constructed by replacing the native promoter
      of the Afpmt2 with the Aspergillus nidulans alcA promoter. Reduced expression of
      the Afpmt2 gene led to a lagged germination, retarded hyphal growth, reduced
      conidiation and defect in cell wall integrity; however, no temperature-sensitive
      growth was observed. Further analysis revealed that reduced expression of the
      Afpmt2 caused a failure of the actin re-arrangement. Our results suggest that
      Afpmt2 gene was required for growth and played a role distinct from that of the
      Afpmt1 in A. fumigatus.

PMID- 20053627
TI  - Heparan sulfate mediates amyloid-beta internalization and cytotoxicity.
AB  - Heparan sulfate (HS) has been found associated with amyloid deposits, including
      the toxic amyloid-beta (Abeta) peptide aggregates in cerebral vasculature and
      neuronal tissues in patients with Alzheimer's disease. However, the
      pathophysiological significance of the HS-Abeta interaction has remained unclear.
      In the present study, we applied cell models to gain insight into the roles of HS
      in relation to Abeta toxicity. Wild-type Chinese hamster ovary (CHO-WT) cells
      showed loss of viability following exposure to Abeta40, whereas the HS-deficient
      cell line, pgsD-677, was essentially resistant. Immunocytochemical analysis
      showed Abeta internalization by CHO-WT, but not pgsD-677 cells. Abeta40 toxicity
      was also attenuated in human embryonic kidney cells overexpressing heparanase.
      Finally, addition of heparin to human umbilical vein endothelial cells prevented
      internalization of added Abeta40 and protected against Abeta toxicity. Taken
      together, these findings suggest that cell-surface HS mediates Abeta
      internalization and toxicity.

PMID- 20053628
TI  - Differential expression of immunomodulatory galectin-1 in peripheral leukocytes
      and adult tissues and its cytosolic organization in striated muscle.
AB  - Galectin-1 (Gal-1) is important in immune function and muscle regeneration, but
      its expression and localization in adult tissues and primary leukocytes remain
      unclear. To address this, we generated a specific monoclonal antibody against Gal
      1, termed alphahGal-1, and defined a sequential peptide epitope that it
      recognizes, which is preserved in human and porcine Gal-1, but not in murine Gal
      1. Using alphahGal-1, we found that Gal-1 is expressed in a wide range of porcine
      tissues, including striated muscle, liver, lung, brain, kidney, spleen, and
      intestine. In most types of cells, Gal-1 exhibits diffuse cytosolic expression,
      but in cells within the splenic red pulp, Gal-1 showed both cytosolic and nuclear
      localization. Gal-1 was also expressed in arterial walls and exhibited prominent
      cytosolic and nuclear staining in cultured human endothelial cells. However,
      human peripheral leukocytes and promyelocytic HL60 cells lack detectable Gal-1
      and also showed very low levels of Gal-1 mRNA. In striking contrast, Gal-1
      exhibited an organized cytosolic staining pattern within striated muscle tissue
      of cardiac and skeletal muscle and colocalized with sarcomeric actin on I bands.
      These results provide insights into previously defined roles for Gal-1 in
      inflammation, immune regulation and muscle biology.

PMID- 20053629
TI  - The novel proapoptotic activity of nonnatural enantiomer of Lentiginosine.
AB  - D-(-)-Lentiginosine [(-)-4], the nonnatural enantiomer of the iminosugar
      indolizidine alkaloid L-(+)-lentiginosine, acts as apoptosis inducer on tumor
      cells of different origin, in contrast to its natural enantiomer. Although D-(-)
      4 exhibited a proapoptotic activity towards tumor cells at level lower than the
      chemotherapeutic agent, SN38, it was less proapoptotic towards normal cells and
      less cytotoxic. Apoptosis induced by D-(-)-4 was caspase-dependent, as shown by
      the increased expression and activity of caspase-3 and -8 in treated cells, and
      by inhibition following treatment with the pan caspase inhibitor, ZVAD-FMK. This
      study highlighted how a natural iminosugar alkaloid and its synthetic enantiomer,
      which were simply known for their inhibition against a fungal glucoamylase, could
      behave in a complete different way when tested towards cell growth and death of
      cells of different origin.

PMID- 20053630
TI  - On the mechanisms of nectar secretion: revisited.
AB  - BACKGROUND AND SCOPE: Models of nectar formation and exudation in multilayered
      nectaries with modified stomata or permeable cuticle are evaluated. In the
      current symplasmic model the pre-nectar moves from terminal phloem through the
      symplasm into the apoplasm (cell walls and intercellular spaces) with nectar
      formation by either granulocrine or eccrine secretion and its diffusion outwards.
      It is concluded, however, that no secretory granules are actually produced by the
      endoplasmic reticulum, and that secretory Golgi vesicles are not involved in the
      transport of nectar sugar. Therefore, the concept of granulocrine secretion of
      nectar should be discarded. The specific function of the endomembrane system in
      nectary cells remains unknown. According to the apoplasmic model, the pre-nectar
      moves from the terminal phloem in the apoplasm and, on the way, is transformed
      from phloem sap into nectar. However, viewed ultrastructurally, the unloading
      (terminal) phloem of nectaries appears to be less active than that of the leaf
      minor veins, and is therefore not actively involved in the secretion of pre
      nectar components into the apoplasm. This invalidates the apoplasmic model.
      Neither model provides an explanation for the origin of the driving force for
      nectar discharge. PROPOSAL: A new model is proposed in which nectar moves by a
      pressure-driven mass flow in the nectary apoplasm while pre-nectar sugars diffuse
      from the sieve tubes through the symplasm to the secretory cells, where nectar is
      formed and sugars cross the plasma membrane by active transport ('eccrine
      secretion'). The pressure originates as the result of water influx in the
      apoplasm from the symplasm along the sugar concentration gradient. It follows
      from this model that there can be no combinations of apoplasmic and symplasmic
      pre-nectar movements. The mass-flow mechanism of nectar exudation appears to be
      universal and applicable to all nectaries irrespective of their type, morphology
      and anatomy, presence or absence of modified stomata, and their own vascular
      system.

PMID- 20053631
TI  - The intracranial aneurysm susceptibility genes HSPG2 and CSPG2 are not associated
      with abdominal aortic aneurysm.
AB  - BACKGROUND: A genetic variant on chromosome 9p21 associates with abdominal aortic
      aneurysm (AAA) and intracranial aneurysm (IA), indicating that despite the
      differences in pathology there are shared genetic risk factors. We investigated
      whether the IA susceptibility genes heparan sulfate proteoglycan 2 (HSPG2) and
      chondroitin sulfate proteoglycan 2 (CSPG2) associate with AAA as well. METHODS:
      Using tag single nucleotide polymorphisms (SNPs), all common variants were
      analyzed in a Dutch AAA case-control population in a 2-stage genotyping approach.
      In stage 1, 12 tag SNPs in HSPG2 and 22 tag SNPs in CSPG2 were genotyped in 376
      patients and 648 controls. Genotyping of significantly associated SNPs was
      replicated in a second independent cohort of 360 cases and 376 controls. RESULTS:
      In stage 1, no HSPG2 SNPs and 1 CSPG2 SNP associated with AAA (rs2652106, P =
      .019). Association of this SNP was not replicated (P = .342). CONCLUSIONS: Our
      findings demonstrate that, in contrast to IA, HSPG2 and CSPG2 do not associate
      with AAA.

PMID- 20053632
TI  - Functional transformation of the chromatoid body in mouse spermatids requires
      testis-specific serine/threonine kinases.
AB  - The cytoplasmic chromatoid body (CB) organizes mRNA metabolism and small
      regulatory RNA pathways, in relation to haploid gene expression, in mammalian
      round spermatids. However, little is known about functions and fate of the CB at
      later steps of spermatogenesis, when elongating spermatids undergo chromatin
      compaction and transcriptional silencing. In mouse elongating spermatids, we
      detected accumulation of the testis-specific serine/threonine kinases TSSK1 and
      TSSK2, and the substrate TSKS, in a ring-shaped structure around the base of the
      flagellum and in a cytoplasmic satellite, both corresponding to structures
      described to originate from the CB. At later steps of spermatid differentiation,
      the ring is found at the caudal end of the newly formed mitochondrial sheath.
      Targeted deletion of the tandemly arranged genes Tssk1 and Tssk2 in mouse
      resulted in male infertility, with loss of the CB-derived ring structure, and
      with elongating spermatids possessing a collapsed mitochondrial sheath. These
      results reveal TSSK1- and TSSK2-dependent functions of a transformed CB in post
      meiotic cytodifferentiation of spermatids.

PMID- 20053633
TI  - Reduced myofibrillar connectivity and increased Z-disk width in nebulin-deficient
      skeletal muscle.
AB  - A prominent feature of striated muscle is the regular lateral alignment of
      adjacent sarcomeres. An important intermyofibrillar linking protein is the
      intermediate filament protein desmin, and based on biochemical and structural
      studies in primary cultures of myocytes it has been proposed that desmin
      interacts with the sarcomeric protein nebulin. Here we tested whether nebulin is
      part of a novel biomechanical linker complex, by using a recently developed
      nebulin knockout (KO) mouse model and measuring Z-disk displacement in adjacent
      myofibrils of both extensor digitorum longus (EDL) and soleus muscle. Z-disk
      displacement increased as sarcomere length (SL) was increased and the increase
      was significantly larger in KO fibers than in wild-type (WT) fibers; results in 3
      day-old and 10-day-old mice were similar. Immunoelectron microscopy revealed
      reduced levels of desmin in intermyofibrillar spaces adjacent to Z-disks in KO
      fibers compared with WT fibers. We also performed siRNA knockdown of nebulin and
      expressed modules within the Z-disk portion of nebulin (M160-M170) in quail
      myotubes and found that this prevented the mature Z-disk localization of desmin
      filaments. Combined, these data suggest a model in which desmin attaches to the Z
      disk through an interaction with nebulin. Finally, because nebulin has been
      proposed to play a role in specifying Z-disk width, we also measured Z-disk width
      in nebulin KO mice. Results show that most Z-disks of KO mice were modestly
      increased in width (approximately 80 nm in soleus and approximately 40 nm in EDL
      fibers) whereas a small subset had severely increased widths (up to approximately
      1 microm) and resembled nemaline rod bodies. In summary, structural studies on a
      nebulin KO mouse show that in the absence of nebulin, Z-disks are significantly
      wider and that myofibrils are misaligned. Thus the functional roles of nebulin
      extend beyond thin filament length regulation and include roles in maintaining
      physiological Z-disk widths and myofibrillar connectivity.

PMID- 20053634
TI  - Weak mitochondrial targeting sequence determines tissue-specific subcellular
      localization of glutamine synthetase in liver and brain cells.
AB  - Evolution of the uricotelic system for ammonia detoxification required a
      mechanism for tissue-specific subcellular localization of glutamine synthetase
      (GS). In uricotelic vertebrates, GS is mitochondrial in liver cells and
      cytoplasmic in brain. Because these species contain a single copy of the GS gene,
      it is not clear how tissue-specific subcellular localization is achieved. Here we
      show that in chicken, which utilizes the uricotelic system, the GS transcripts of
      liver and brain cells are identical and, consistently, there is no difference in
      the amino acid sequence of the protein. The N-terminus of GS, which constitutes a
      'weak' mitochondrial targeting signal (MTS), is sufficient to direct a chimeric
      protein to the mitochondria in hepatocytes and to the cytoplasm in astrocytes.
      Considering that a weak MTS is dependent on a highly negative mitochondrial
      membrane potential (DeltaPsi) for import, we examined the magnitude of DeltaPsi
      in hepatocytes and astrocytes. Our results unexpectedly revealed that DeltaPsi in
      hepatocytes is considerably more negative than that of astrocytes and that
      converting the targeting signal into 'strong' MTS abolished the capability to
      confer tissue-specific subcellular localization. We suggest that evolutional
      selection of weak MTS provided a tool for differential targeting of an identical
      protein by taking advantage of tissue-specific differences in DeltaPsi.

PMID- 20053636
TI  - LRP6 is internalized by Dkk1 to suppress its phosphorylation in the lipid raft
      and is recycled for reuse.
AB  - Beta-catenin-mediated Wnt signaling is crucial in animal development and tumor
      progression. The phosphorylation of low-density lipoprotein receptor-related
      protein 6 (LRP6), a single-span transmembrane Wnt receptor, plays a vital role in
      this signaling. Dickkopf1 (Dkk1) has been shown to inhibit the Wnt-beta-catenin
      pathway, but the mechanism is not yet clear. Here, evidence is presented that
      Wnt3a-dependent phosphorylation of LRP6 occurs in the lipid raft and that Dkk1
      inhibits the formation of a complex between LRP6 and casein kinase 1gamma
      (CK1gamma) by removing LRP6 from the lipid raft. Dkk1 internalized LRP6 in a Rab5
      dependent mechanism to prevent phosphorylation mediated by CK1gamma. The
      internalized LRP6 was recycled back in a Rab11-dependent mechanism to the cell
      surface membrane, and the recycled LRP6 again responded to Wnt3a and Dkk1.
      Internalized Dkk1 was trafficked in a Rab7-mediated route and degraded in the
      lysosome. These results suggest that Dkk1 induces the internalization of LRP6 to
      suppress its phosphorylation in the lipid raft and allows subsequent recycling of
      LRP6 so that it can be reused for signaling.

PMID- 20053635
TI  - Dynamic regulation of ROCK in tumor cells controls CXCR4-driven adhesion events.
AB  - CXCR4 is a chemokine receptor often found aberrantly expressed on metastatic
      tumor cells. To investigate CXCR4 signaling in tumor cell adhesion, we stably
      overexpressed CXCR4 in MCF7 breast tumor cells. Cell attachment assays
      demonstrate that stimulation of the receptor with its ligand, CXCL12, promotes
      adhesion of MCF7-CXCR4 cells to both extracellular matrix and endothelial
      ligands. To more closely mimic the conditions experienced by a circulating tumor
      cell, we performed the attachment assays under shear stress conditions. We found
      that CXCL12-induced tumor cell attachment is much more pronounced under flow.
      ROCK is a serine/threonine kinase associated with adhesion and metastasis, which
      is regulated by CXCR4 signaling. Thus, we investigated the contribution of ROCK
      activity during CXC12-induced adhesion events. Our results demonstrate a biphasic
      regulation of ROCK in response to adhesion. During the initial attachment,
      inhibition of ROCK activity is required. Subsequently, re-activation of ROCK
      activity is required for maturation of adhesion complexes and enhanced tumor cell
      migration. Interestingly, CXCL12 partially reduces the level of ROCK activity
      generated by attachment, which supports a model in which stimulation with CXCL12
      regulates tumor cell adhesion events by providing an optimal level of ROCK
      activity for effective migration.

PMID- 20053637
TI  - Novel Staufen1 ribonucleoproteins prevent formation of stress granules but favour
      encapsidation of HIV-1 genomic RNA.
AB  - Human immunodeficiency virus type 1 (HIV-1) Gag selects for and mediates genomic
      RNA (vRNA) encapsidation into progeny virus particles. The host protein, Staufen1
      interacts directly with Gag and is found in ribonucleoprotein (RNP) complexes
      containing vRNA, which provides evidence that Staufen1 plays a role in vRNA
      selection and encapsidation. In this work, we show that Staufen1, vRNA and Gag
      are found in the same RNP complex. These cellular and viral factors also
      colocalize in cells and constitute novel Staufen1 RNPs (SHRNPs) whose assembly is
      strictly dependent on HIV-1 expression. SHRNPs are distinct from stress granules
      and processing bodies, are preferentially formed during oxidative stress and are
      found to be in equilibrium with translating polysomes. Moreover, SHRNPs are
      stable, and the association between Staufen1 and vRNA was found to be evident in
      these and other types of RNPs. We demonstrate that following Staufen1 depletion,
      apparent supraphysiologic-sized SHRNP foci are formed in the cytoplasm and in
      which Gag, vRNA and the residual Staufen1 accumulate. The depletion of Staufen1
      resulted in reduced Gag levels and deregulated the assembly of newly synthesized
      virions, which were found to contain several-fold increases in vRNA, Staufen1 and
      other cellular proteins. This work provides new evidence that Staufen1-containing
      HIV-1 RNPs preferentially form over other cellular silencing foci and are
      involved in assembly, localization and encapsidation of vRNA.

PMID- 20053638
TI  - Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere
      protein F.
AB  - Progression through mitosis and cytokinesis requires the sequential proteolysis
      of several cell-cycle regulators. This proteolysis is mediated by the ubiquitin
      proteasome system, with the E3 ligase being the anaphase-promoting complex, also
      known as the cyclosome (APC/C). The APC/C is regulated by two activators, namely
      Cdc20 and Cdh1. The current view is that prior to anaphase, the APC/C is
      activated by Cdc20, but that following anaphase, APC/C switches to Cdh1-dependent
      activation. However, here we present an analysis of the kinetochore protein Cenp
      F that is inconsistent with this notion. Although it has long been appreciated
      that Cenp-F is degraded sometime during or after mitosis, exactly when and how
      has not been clear. Here we show that degradation of Cenp-F initiates about six
      minutes after anaphase, and that this is dependent on a C-terminal KEN-box.
      Although these two observations are consistent with Cenp-F being a substrate of
      Cdh1-activated APC/C, Cenp-F is degraded normally in Cdh1-null cells. By
      contrast, RNAi-mediated repression of APC/C subunits or Cdc20 does inhibit Cenp-F
      degradation. These findings therefore suggest that the APC/C does not simply
      'switch' upon anaphase onset; rather, our observations indicate that Cdc20 also
      contributes to post-anaphase activation of the APC/C. We also show that the post
      anaphase, KEN-box-dependent degradation of Cenp-F requires it to be farnesylated,
      a post-translational modification usually linked to membrane association. Because
      so many of the behaviours of Cenp-F are farnesylation-dependent, we suggest that
      this modification plays a more global role in Cenp-F function.

PMID- 20053639
TI  - Pollen-tube tip growth requires a balance of lateral propagation and global
      inhibition of Rho-family GTPase activity.
AB  - Rapid tip growth allows for efficient development of highly elongated cells (e.g.
      neuronal axons, fungal hyphae and pollen tubes) and requires an elaborate
      spatiotemporal regulation of the growing region. Here, we use the pollen tube as
      a model to investigate the mechanism regulating the growing region. ROPs (Rho
      related GTPases from plants) are essential for pollen tip growth and display
      oscillatory activity changes in the apical plasma membrane (PM). By manipulating
      the ROP activity level, we showed that the PM distribution of ROP activity as an
      apical cap determines the tip growth region and that efficient tip growth
      requires an optimum level of the apical ROP1 activity. Excessive ROP activation
      induced the enlargement of the tip growth region, causing growth depolarization
      and reduced tube elongation. Time-lapse analysis suggests that the apical ROP1
      cap is generated by lateral propagation of a localized ROP activity. Subcellular
      localization and gain- and loss-of-function analyses suggest that RhoGDI- and
      RhoGAP-mediated global inhibition limits the lateral propagation of apical ROP1
      activity. We propose that the balance between the lateral propagation and the
      global inhibition maintains an optimal apical ROP1 cap and generates the apical
      ROP1 activity oscillation required for efficient pollen-tube elongation.

PMID- 20053640
TI  - ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers
      (diabodies).
AB  - Rapid clearing engineered antibody fragments for immunoPET promise high
      sensitivity at early time points. Here, tumor targeting of anti-CD20 diabodies
      (scFv dimers) for detection of low-grade B-cell lymphomas were evaluated. In
      addition, the effect of linker length on oligomerization of the diabody was
      investigated. Four rituximab scFv variants in the V(L)-V(H) orientation with
      different linker lengths between the V domains (scFv-1, scFv-3, scFv-5, scFv-8),
      plus the scFv-5 with a C-terminal cysteine (Cys-Db) for site-specific
      modification were generated. The scFv-8 and Cys-Db were radioiodinated with
      (124)I for PET imaging, and biodistribution of (131)I-Cys-Db was carried out at
      2, 4 10 and 20 h. The five anti-CD20 scFv variants were expressed as fully
      functional dimers. Shortening the linker to three or one residue did not produce
      higher order of multimers. Both (124)I-labeled scFv-8 and Cys-Db exhibited
      similar tumor targeting at 8 h post injection, with significantly higher uptakes
      than in control tumors (P < 0.05). At 20 h, less than 1% ID/g of (131)I-labeled
      Cys-Db was present in tumors and tissues. Specific tumor targeting and high
      contrast images were achieved with the anti-CD20 diabodies. These agents extend
      the repertoire of reagents that can potentially be used to improve detection of
      low-grade lymphomas.

PMID- 20053641
TI  - The energetic basis of acoustic communication.
AB  - Animals produce a tremendous diversity of sounds for communication to perform
      life's basic functions, from courtship and parental care to defence and foraging.
      Explaining this diversity in sound production is important for understanding the
      ecology, evolution and behaviour of species. Here, we present a theory of
      acoustic communication that shows that much of the heterogeneity in animal vocal
      signals can be explained based on the energetic constraints of sound production.
      The models presented here yield quantitative predictions on key features of
      acoustic signals, including the frequency, power and duration of signals.
      Predictions are supported with data from nearly 500 diverse species (e.g.
      insects, fishes, reptiles, amphibians, birds and mammals). These results indicate
      that, for all species, acoustic communication is primarily controlled by
      individual metabolism such that call features vary predictably with body size and
      temperature. These results also provide insights regarding the common energetic
      and neuromuscular constraints on sound production, and the ecological and
      evolutionary consequences of producing these sounds.

PMID- 20053642
TI  - Systemic factors dominate mammal protein evolution.
AB  - Proteins encoded by highly expressed genes evolve more slowly. This correlation
      is thought to arise owing to purifying selection against toxicity of misfolded
      proteins (that should be more crucial for highly expressed genes). It is now
      widely accepted that this individual (by-gene) effect is a dominant cause in
      protein evolution. Here, I show that in mammals, the evolutionary rate of a
      protein is much more strongly related to the evolutionary rate of coexpressed
      proteins (and proteins of the same biological pathway) than to the expression
      level of its encoding gene. The complexity of gene regulation (estimated by the
      numbers of transcription factor targets and regulatory microRNA targets in the
      encoding gene) is another important cause, which is much stronger than gene
      expression level. Proteins encoded by complexly regulated genes evolve more
      slowly. The intronic length and the ratio of intronic to coding sequence lengths
      also correlate negatively with protein evolutionary rate (which contradicts the
      expectation from the negative link between expression level and evolutionary
      rate). One more important factor, which is much stronger than gene expression
      level, is evolutionary age. More recent proteins evolve faster, and expression
      level of an encoding gene becomes quite a minor cause in the evolution of mammal
      proteins of metazoan origin. These data suggest that, in contrast to a widespread
      opinion, systemic factors dominate mammal protein evolution.

PMID- 20053643
TI  - Behavioural consequences of sensory plasticity in guppies.
AB  - Sensory plasticity, whereby individuals compensate for sensory deprivation in one
      sense by an improvement in the performance of an alternative sense, is a well
      documented phenomenon in nature. Despite this, the behavioural and ecological
      consequences of sensory plasticity have not been addressed. Here we show
      experimentally that some components (vision and chemoreception) of the sensory
      system of guppies are developmentally plastic, and that this plasticity has
      important consequences for foraging behaviour. Guppies reared under low light
      conditions had a significantly stronger response to chemical food cues
      encountered in isolation than fish reared at higher light levels. Conversely,
      they exhibited a weaker response to visual-only cues. When visual and
      olfactory/gustatory cues were presented together, no difference between the
      strength of response for fish reared at different light intensities was evident.
      Our data suggest that guppies can compensate for experience of a visually poor,
      low light environment via a sensory switch from vision to olfaction/gustation.
      This switch from sight to chemoreception may allow individuals to carry out the
      foraging behaviour that is essential to their survival in a visually poor
      environment. These considerations are especially important given the increasing
      frequency of anthropogenic changes to ecosystems. Compensatory phenotypic
      plasticity as demonstrated by our study may provide a hitherto unconsidered
      buffer that could allow animals to perform fundamental behaviours in the face of
      considerable change to the sensory environment.

PMID- 20053644
TI  - Learning your own strength: winner and loser effects should change with age and
      experience.
AB  - Winner and loser effects, in which the outcome of an aggressive encounter
      influences the tendency to escalate future conflicts, have been documented in
      many taxa, but we have limited understanding of why they have evolved. One
      possibility is that individuals use previous victories and defeats to assess
      their fighting ability relative to others. We explored this idea by modelling a
      population of strong and weak individuals that do not know their own strength,
      but keep track of how many fights they have won. Under these conditions, adaptive
      behaviour generates clear winner and loser effects: individuals who win fights
      should escalate subsequent conflicts, whereas those who lose should retreat from
      aggressive opponents. But these effects depend strongly on age and experience.
      Young, naive individuals should show highly aggressive behaviour and pronounced
      loser effects. For these inexperienced individuals, fighting is especially
      profitable because it yields valuable information about their strength.
      Aggression should then decline as an individual ages and gains experience, with
      those who lose fights becoming more submissive. Older individuals, who have a
      better idea of their own strength, should be more strongly influenced by
      victories than losses. In conclusion, we predict that both aggressiveness and the
      relative magnitude of winner and loser effects should change with age, owing to
      changes in how individuals perceive their own strength.

PMID- 20053645
TI  - Microscale laser surgery reveals adaptive function of male intromittent
      genitalia.
AB  - The leading hypothesis for the evolution of male genital complexity proposes that
      genital traits evolve in response to post-insemination sexual selection; that is,
      via cryptic female choice or sperm competition. Here, we describe a laser
      ablation technique for high-precision manipulation of microscale body parts of
      insects, and employ it to discern the adaptive function of a rapidly evolving and
      taxonomically important genital trait: the intromittent claw-like genital spines
      of male Drosophila bipectinata Duda. We demonstrate experimentally and
      unambiguously that the genital spines of this species function to mechanically
      couple the genitalia together. The excision of the spines by laser ablation
      sharply reduced the ability of males both to copulate and to compete against
      rival males for mates. When spineless males did succeed to copulate, their
      insemination success and fertilization rate were not statistically different from
      controls, at odds with the post-insemination sexual selection hypothesis of
      genital function and evolution. The results provide direct experimental support
      for the hypothesis that genital traits evolve in response to sexual selection
      occurring prior to insemination.

PMID- 20053646
TI  - Tool use by wild New Caledonian crows Corvus moneduloides at natural foraging
      sites.
AB  - New Caledonian crows Corvus moneduloides use tools made from sticks or leaf stems
      to 'fish' woodboring beetle larvae from their burrows in decaying wood. Previous
      research on this behaviour has been confined to baited sites, leaving its
      ecological context and significance virtually unexplored. To obtain detailed
      observations of natural, undisturbed tool use, we deployed motion-triggered video
      cameras at seven larva-fishing sites. From 1797 camera hours of surveillance over
      111 days, we recorded 317 site visits by at least 14 individual crows. Tool use
      was observed during 150 site visits. Our video footage revealed notable variation
      in foraging success among identifiable crows. Two nutritionally independent,
      immature crows spent considerable time using tools, but were much less successful
      than local adults, highlighting the potential role of individual and social
      learning in the acquisition of tool-use proficiency. During systematic surveys of
      larva-fishing sites, we collected 193 tools that crows had left inserted in larva
      burrows. Comparing these tools with the holes in which they were found, and with
      raw materials available around logs, provides evidence for tool selectivity by
      New Caledonian crows under natural conditions. Taken together, these two
      complementary lines of investigation provide, to our knowledge, the first
      quantitative description of larva fishing by wild crows in its full ecological
      context.

PMID- 20053647
TI  - Aggression, segregation and stability in a dominance hierarchy.
AB  - Central to our understanding of social group formation and maintenance is the
      question of how within-group conflict resolution is achieved in the face of
      asymmetrical competition over resources and reproduction. A crucial yet implicit
      assumption of many conflict resolution models dealing with reproductive skew is
      that subordinates have perfect knowledge of the extent of conflict between
      themselves and their dominants, enabling behavioural responses on an individual
      rather than evolutionary scale. However, a mechanism enabling subordinates to
      accurately assess their relative conflict levels has yet to be empirically
      demonstrated. Here, we show in the angelfish Centropyge bicolor that the rate of
      overt mild aggression from dominants to subordinates acts as a signal of
      increasing rank conflict. The clarity of this signal can be reduced by spatial
      segregation, causing subordinates to be less able to respond appropriately by
      regulation of their foraging rates. A reduced signal ultimately leads to a less
      well-defined dominance hierarchy and destabilization of the social group. Our
      study suggests that, contrary to previous suggestions, dominant aggression rates
      play a crucial role as an accurate information signal required for the
      evolutionary stability of skew models.

PMID- 20053648
TI  - A mathematical model of exposure of non-target Lepidoptera to Bt-maize pollen
      expressing Cry1Ab within Europe.
AB  - Genetically modified (GM) maize MON810 expresses a Cry1Ab insecticidal protein,
      derived from Bacillus thuringiensis (Bt), toxic to lepidopteran target pests such
      as Ostrinia nubilalis. An environmental risk to non-target Lepidoptera from this
      GM crop is exposure to harmful amounts of Bt-containing pollen deposited on host
      plants in or near MON810 fields. An 11-parameter mathematical model analysed
      exposure of larvae of three non-target species: the butterflies Inachis io (L.),
      Vanessa atalanta (L.) and moth Plutella xylostella (L.), in 11 representative
      maize cultivation regions in four European countries. A mortality-dose
      relationship was integrated with a dose-distance relationship to estimate
      mortality both within the maize MON810 crop and within the field margin at
      varying distances from the crop edge. Mortality estimates were adjusted to allow
      for physical effects; the lack of temporal coincidence between the susceptible
      larval stage concerned and the period over which maize MON810 pollen is shed; and
      seven further parameters concerned with maize agronomy and host-plant ecology.
      Sublethal effects were estimated and allowance made for aggregated pollen
      deposition. Estimated environmental impact was low: in all regions, the
      calculated mortality rate for worst-case scenarios was less than one individual
      in every 1572 for the butterflies and one in 392 for the moth.

PMID- 20053649
TI  - Moonlight avoidance in gerbils reveals a sophisticated interplay among time
      allocation, vigilance and state-dependent foraging.
AB  - Foraging animals have several tools for managing the risk of predation, and the
      foraging games between them and their predators. Among these, time allocation is
      foremost, followed by vigilance and apprehension. Together, their use influences
      a forager's time allocation and giving-up density (GUD) in depletable resource
      patches. We examined Allenby's gerbils (Gerbilus andersoni allenbyi) exploiting
      seed resource patches in a large vivarium under varying moon phases in the
      presence of a red fox (Vulpes vulpes). We measured time allocated to foraging
      patches electronically and GUDs from seeds left behind in resource patches. From
      these, we estimated handling times, attack rates and quitting harvest rates
      (QHRs). Gerbils displayed greater vigilance (lower attack rates) at brighter moon
      phases (full < wane < wax < new). Similarly, they displayed higher GUDs at
      brighter moon phases (wax > full > new > wane). Finally, gerbils displayed higher
      QHRs at new and waxing moon phases. Differences across moon phases not only
      reflect changing time allocation and vigilance, but changes in the state of the
      foragers and their marginal value of energy. Early in the lunar cycle, gerbils
      rely on vigilance and sacrifice state to avoid risk; later they defend state at
      the cost of increased time allocation; finally their state can recover as safe
      opportunities expand. In the predator-prey foraging game, foxes may contribute to
      these patterns of behaviours by modulating their own activity in response to the
      opportunities presented in each moon phase.

PMID- 20053650
TI  - Pattern mimicry of host eggs by the common cuckoo, as seen through a bird's eye.
AB  - Cuckoo-host interactions provide classical examples of coevolution. Cuckoos place
      hosts under selection to detect and reject foreign eggs, while host defences
      result in the evolution of host-egg mimicry in cuckoos. Despite a long history of
      research, egg pattern mimicry has never been objectively quantified, and so its
      coevolution with host defences has not been properly assessed. Here, we use
      digital image analysis and modelling of avian vision to quantify the level of
      pattern mimicry in eight host species of the common cuckoo Cuculus canorus and
      their respective cuckoo host-races. We measure a range of pattern attributes,
      including marking size, diversity in size, contrast, coverage and dispersion.
      This new technique reveals hitherto unnoticed sophistication in egg pattern
      mimicry. We show that various features of host egg pattern are mimicked by the
      eggs of their respective cuckoo host-races, and that cuckoos have evolved better
      pattern mimicry for host species that exhibit stronger egg rejection. Pattern
      differs relatively more between eggs of different host species than between their
      respective cuckoo host-races. We suggest that cuckoos may have more 'average'
      markings in order to be able to use subsidiary hosts. Our study sheds new light
      on cuckoo-host coevolution and illustrates a new technique for quantifying animal
      markings with respect to the relevant animal visual system.

PMID- 20053651
TI  - The direct effects of increasing CO2 and temperature on non-calcifying organisms:
      increasing the potential for phase shifts in kelp forests.
AB  - Predictions about the ecological consequences of oceanic uptake of CO(2) have
      been preoccupied with the effects of ocean acidification on calcifying organisms,
      particularly those critical to the formation of habitats (e.g. coral reefs) or
      their maintenance (e.g. grazing echinoderms). This focus overlooks the direct
      effects of CO(2) on non-calcareous taxa, particularly those that play critical
      roles in ecosystem shifts. We used two experiments to investigate whether
      increased CO(2) could exacerbate kelp loss by facilitating non-calcareous algae
      that, we hypothesized, (i) inhibit the recovery of kelp forests on an urbanized
      coast, and (ii) form more extensive covers and greater biomass under moderate
      future CO(2) and associated temperature increases. Our experimental removal of
      turfs from a phase-shifted system (i.e. kelp- to turf-dominated) revealed that
      the number of kelp recruits increased, thereby indicating that turfs can inhibit
      kelp recruitment. Future CO(2) and temperature interacted synergistically to have
      a positive effect on the abundance of algal turfs, whereby they had twice the
      biomass and occupied over four times more available space than under current
      conditions. We suggest that the current preoccupation with the negative effects
      of ocean acidification on marine calcifiers overlooks potentially profound
      effects of increasing CO(2) and temperature on non-calcifying organisms.

PMID- 20053652
TI  - Irradiance governs exploitation of fungi: fine-tuning of carbon gain by two
      partially myco-heterotrophic orchids.
AB  - While all members of the Orchidaceae are fully dependent on mycorrhizal fungi
      during their achlorophyllous juvenile stages, mature plants may remain fully myco
      heterotrophic, become fully autotrophic or develop a nutritional mode where the
      carbon gain through photosynthesis is complemented by organic carbon from fungal
      partners. This so-called partial myco-heterotrophy is intriguingly complex.
      Current knowledge indicates a large range in the proportion of fungus-derived
      carbon between and within partially myco-heterotrophic plant species. However,
      the driving factors for this variation are so far mostly unknown. Here we show
      for two green species of the orchid genus Cephalanthera that light availability
      is the major determinant of the degree of myco-heterotrophy. Using leaf stable
      isotope natural abundance analysis together with time-integrated microscale light
      climate monitoring we could demonstrate that there is a sensitive reaction to
      varying light availability within forests. Low light levels result in strong myco
      heterotrophy while higher irradiances successively drive the orchids towards
      autotrophy. Our results demonstrate that partial myco-heterotrophy in these
      species is not a static nutritional mode but a flexible mechanism driven by light
      availability which allows a balanced usage of carbon resources available in
      nature.

PMID- 20053653
TI  - Lateralization of magnetic compass orientation in pigeons.
AB  - The aim of our study was to test for lateralization of magnetic compass
      orientation in pigeons. Having shown that pigeons are capable of learning
      magnetic compass directions in an operant task, we wanted to know whether the
      brain hemispheres contribute differently and how the lateralization pattern
      relates to findings in other avian species. Birds that had learnt to locate food
      in an operant chamber by means of magnetic directions were tested for
      lateralization of magnetic compass orientation by temporarily covering one eye.
      Successful orientation occurred under all conditions of viewing. Thus, pigeons
      can perceive and process magnetic compass directions with the right eye and left
      brain hemisphere as well as the left eye and right brain hemisphere. However,
      while the right brain hemisphere tended to confuse the learned direction with its
      opposite (axial response), the left brain hemisphere specifically preferred the
      correct direction. Our findings demonstrate bilateral processing of magnetic
      information, but also suggest qualitative differences in how the left and the
      right brain deal with magnetic cues.

PMID- 20053654
TI  - A minimum of two distinct heritable factors are required to explain correlation
      structures in proliferating lymphocytes.
AB  - During the adaptive immune response, lymphocyte populations undergo a
      characteristic three-phase process: expansion through a series of cell divisions;
      cessation of expansion; and, finally, most of the accumulated lymphocytes die by
      apoptosis. The data used, thus far, to inform understanding of these processes,
      both in vitro and in vivo, are taken from flow cytometry experiments. One
      significant drawback of flow cytometry is that individual cells cannot be
      tracked, so that it is not possible to investigate interdependencies in the fate
      of cells within a family tree. This deficit in experimental information has
      recently been overcome by Hawkins et al. (Hawkins et al. 2009 Proc. Natl Acad.
      Sci. USA 106, 13 457-13 462 (doi:10.1073/pnas.0905629106)), who reported on time
      lapse microscopy experiments in which B-cells were stimulated through the TLR-9
      receptor. Cells stimulated in this way do not aggregate, so that data regarding
      family trees can be recorded. In this article, we further investigate the Hawkins
      et al. data. Our conclusions are striking: in order to explain the familial
      correlation structure in division times, death times and propensity to divide, a
      minimum of two distinct heritable factors are necessary. As the data show that
      two distinct factors are necessary, we develop a stochastic model that has two
      heritable factors and demonstrate that it can reproduce the key features of the
      data. This model shows that two heritable factors are sufficient. These
      deductions have a clear impact upon biological understanding of the adaptive
      immune response. They also necessitate changes to the fundamental premises behind
      the tools developed by statisticians to draw deductions from flow cytometry data.
      Finally, they affect the mathematical modelling paradigms that are used to study
      these systems, as these are widely developed based on assumptions of cellular
      independence that are not accurate.

PMID- 20053655
TI  - Nonlinear elasticity of biological tissues with statistical fibre orientation.
AB  - The elastic strain energy potential for nonlinear fibre-reinforced materials is
      customarily obtained by superposition of the potentials of the matrix and of each
      family of fibres. Composites with statistically oriented fibres, such as
      biological tissues, can be seen as being reinforced by a continuous infinity of
      fibre families, the orientation of which can be represented by means of a
      probability density function defined on the unit sphere (i.e. the solid angle).
      In this case, the superposition procedure gives rise to an integral form of the
      elastic potential such that the deformation features in the integral, which
      therefore cannot be calculated a priori. As a consequence, an analytical use of
      this potential is impossible. In this paper, we implemented this integral form of
      the elastic potential into a numerical procedure that evaluates the potential,
      the stress and the elasticity tensor at each deformation step. The numerical
      integration over the unit sphere is performed by means of the method of spherical
      designs, in which the result of the integral is approximated by a suitable sum
      over a discrete subset of the unit sphere. As an example of application, we
      modelled the collagen fibre distribution in articular cartilage, and used it in
      simulating displacement-controlled tests: the unconfined compression of a
      cylindrical sample and the contact problem in the hip joint.

PMID- 20053656
TI  - A diagnostic odyssey: detection of an unusual anterior papillary muscle of the
      tricuspid valve.
AB  - A routine chest X-ray in a 78-year-old female patient suggested a retained
      vascular catheter in the right ventricle (RV). On transthoracic echocardiography,
      a prominent linear echo was found in the RV and the patient was referred for
      cardiac computed tomography and magnetic resonance imaging. Although neither of
      these tests showed evidence of a retained foreign body in the RV, they could not
      clarify the nature of the linear structure within the RV cavity. Finally,
      transesophageal echocardiography, using a matrix array three-dimensional probe
      solved the mystery: the linear structure in question within the RV was a large
      papillary muscle with attachments to the anterior leaflet of the tricuspid valve
      and an unusual origin from the interventricular septum.

PMID- 20053657
TI  - Left ventricular torsional dynamics in aortic stenosis: relationship between left
      ventricular untwisting and filling pressures. A two-dimensional speckle tracking
      study.
AB  - AIMS: The contribution of left ventricular (LV) untwisting to LV suction and
      early-diastolic filling was previously demonstrated, but this was not yet tested
      in patients with aortic stenosis (AS). We sought to assess the relationship
      between LV untwisting and LV filling pressures in patients with severe AS and
      normal left ventricular ejection fraction (LVEF) using speckle tracking
      echocardiography. METHODS AND RESULTS: Sixty-one consecutive patients (66 +/- 9
      years) with severe AS, preserved LVEF (63 +/- 6%), and 40 normal subjects (47 +/-
      12 years) were prospectively enrolled. A comprehensive echocardiographic
      examination was performed in all. LV rotation and twisting were assessed using
      speckle tracking echocardiography. Peak apical back rotation rate, peak LV
      untwisting rate, and time intervals from QRS onset (ECG) to each of them were
      measured. Brain natriuretic peptide (BNP) levels were determined in 30 patients.
      Patients with AS were older than normal subjects (P < 0.001). LV mass, LA volume,
      LV filling pressures as well as peak apical back rotation rate and time to peak
      apical back rotation rate were increased in patients (P < 0.05 for all). In
      patients with AS, both time to peak LV untwisting rate and time to peak apical
      back rotation rate were significantly related to E/E' ratio and to BNP levels (P
      < 0.04 for all). CONCLUSION: In patients with severe AS and preserved LVEF, there
      is a significant relationship between LV untwisting and LV filling pressures,
      suggesting a role for impaired LV untwisting in the pathophysiology of diastolic
      dysfunction in this setting.

PMID- 20053658
TI  - Cardioprotection by GSK-3 inhibition: role of enhanced glycogen synthesis and
      attenuation of calcium overload.
AB  - AIMS: Glycogen synthase kinase-3 (GSK-3) is a multi-functional kinase that
      regulates signalling pathways affecting glycogen metabolism, protein synthesis,
      mitosis, and apoptosis. GSK-3 inhibition limits cardiac ischaemia-reperfusion
      (IR) injury, but mechanisms are not clearly defined. This study tested the
      hypothesis that acute GSK-3 inhibition stimulates glycogen synthesis,
      repartitions glucose away from glycolysis, reduces proton (H+) production from
      glucose metabolism, and attenuates intracellular Ca2+ (Ca2+(i)) overload. METHODS
      AND RESULTS: In isolated perfused working rat hearts subjected to global
      ischaemia and reperfusion, the selective GSK-3 inhibitor, SB-216763 (SB, 3
      micromol/L), when added either prior to ischaemia or at the onset of reperfusion,
      improved recovery of left-ventricular (LV) work. SB increased glycogen synthesis
      during reperfusion while glycolysis and H+ production were reduced. Rates of
      glucose and palmitate oxidation were improved by SB. Measurement of Ca2+(i)
      concentration by rapid acquisition indo-1 fluorescence imaging showed that SB,
      when added either prior to ischaemia or at the onset of reperfusion, reduced
      diastolic Ca2+(i) overload during reperfusion. In aerobic hearts depleted of
      glycogen by substrate-free perfusion to a level similar to that measured at the
      onset of reperfusion, SB accelerated glycogen synthesis and reduced glycolysis
      and H+ production independent of changes in LV work. CONCLUSION: Our study
      indicates that reduction in H+ production by GSK-3 inhibition is an early and
      upstream event that lessens Ca2+(i) overload during ischaemia and early
      reperfusion independent of LV work which enhances the recovery of post-ischaemic
      LV function and that may ultimately contribute to previously observed reductions
      in cell death and infarction.

PMID- 20053659
TI  - Molecular cues guiding inflammatory responses.
AB  - Alarm signals generated at inflammatory foci reach the vascular lumen to attract
      immune cells towards the affected tissue. Different leucocyte subsets decipher
      and integrate these complex signals in order to make adequate decisions for their
      migration towards the inflamed tissue. Soluble cues (cytokines and chemokines)
      and membrane receptors in both endothelium and leucocytes orchestrate the
      coordinated recruitment of specific inflammatory cell subsets. All these
      molecules are spatio-temporally organized in specialized structures at the
      luminal side of endothelium and the leucocyte membrane or are generated as
      chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and
      their receptors as well as adhesion molecules expressed by each leucocyte subset
      determine their recruitment for participation in specific inflammatory
      pathologies. Whenever inflammatory signals are altered or misprocessed,
      inflammation can become chronic, causing extensive tissue damage. To combat
      chronic inflammation and autoimmune diseases, novel therapeutic strategies
      attempt to silence the predominant signals in each inflammatory scenario. In this
      review, we provide a general overview of all these aspects related to the
      molecular regulation of leucocyte guidance in inflammatory responses.

PMID- 20053660
TI  - Deep-ocean origin of the freshwater eels.
AB  - Of more than 800 species of eels of the order Anguilliformes, only freshwater
      eels (genus Anguilla with 16 species plus three subspecies) spend most of their
      lives in freshwater during their catadromous life cycle. Nevertheless, because
      their spawning areas are located offshore in the open ocean, they migrate back to
      their specific breeding places in the ocean, often located thousands of
      kilometres away. The evolutionary origin of such enigmatic behaviour, however,
      remains elusive because of the uncertain phylogenetic position of freshwater eels
      within the principally marine anguilliforms. Here, we show strong evidence for a
      deep oceanic origin of the freshwater eels, based on the phylogenetic analysis of
      whole mitochondrial genome sequences from 56 species representing all of the 19
      anguilliform families. The freshwater eels occupy an apical position within the
      anguilliforms, forming a highly supported monophyletic group with various oceanic
      midwater eel species. Moreover, reconstruction of the growth habitats on the
      resulting tree unequivocally indicates an origination of the freshwater eels from
      the midwater of the deep ocean. This shows significant concordance with the
      recent collection of mature adults of the Japanese eel in the upper midwater of
      the Pacific, suggesting that they have retained their evolutionary origin as a
      behavioural trait in their spawning areas.

PMID- 20053661
TI  - Turgid female toads give males the slip: a new mechanism of female mate choice in
      the Anura.
AB  - In many anuran species, males vocalize to attract females but will grasp any
      female that comes within reach and retain their hold unless displaced by a rival
      male. Thus, female anurans may face strong selection to repel unwanted suitors,
      but no mechanism is known for doing so. We suggest that a defensive trait (the
      ability to inflate the body to ward off attack) has been co-opted for this role:
      by inflating their bodies, females are more difficult for males to grasp and
      hence, it is easier for another male to displace an already amplexed rival.
      Inflating a model female cane toad (Bufo marinus) strongly reduced a male's
      ability to maintain amplexus; and females who were experimentally prevented from
      inflating their bodies experienced no successful takeovers from rival males, in
      contrast to control females. Thus, the ability of a female cane toad to inflate
      her body may allow her to manipulate the outcome of male-male competition. This
      overlooked mechanism of anuran mate choice may reflect a common evolutionary
      pattern, whereby females co-opt defensive traits for use in sexual selection.

PMID- 20053662
TI  - Attention to elders' voice in non-human primates.
AB  - The observed respect and attention to elders' speech in traditional cultures
      appears to have a 'universal' component which questions its possible biological
      bases. Animals present differential attention to the vocalizations of other
      individuals according to their characteristics but little is known about the
      potential propensity to pay more attention to vocalizations of elders. On the
      basis of several hundreds of vocal exchanges recorded, here we show that aged
      female Campbell's monkeys (Cercopithecus campbelli), despite being significantly
      less 'loquacious' than their younger adult counterparts, elicit many more
      responses when calling. These findings show that attention to elders' vocal
      production appears in non-human primates, leading to new lines of questioning on
      human culture and language evolution.

PMID- 20053663
TI  - Group provisioning limits sharing conflict among nestlings in joint-nesting
      Taiwan yuhinas.
AB  - Offspring often compete over limited available resources. Such sibling
      competition may be detrimental to parents both because it entails wasted
      expenditure and because it allows stronger offspring to obtain a disproportionate
      share of resources. We studied nestling conflict over food and its resolution in
      a joint-nesting species of bird, the Taiwan yuhina (Yuhina brunneiceps). We show
      that adult yuhinas coordinate their feeding visits, and that this coordination
      limits competition among nestlings, leading to a 'fairer' division of resources.
      Transponder identification and video-recording systems were used to observe adult
      feeding and nestling begging behaviours. We found that: (i) yuhinas feed
      nestlings more often in large parties than in small parties; (ii) feeding events
      occurred non-randomly in bouts of very short intervals; and (iii) food
      distribution among nestlings was more evenly distributed, and fewer nestlings
      begged, during large-party feeding bouts compared with small-party feeding bouts.
      To our knowledge, this is the first study in a cooperative breeding species
      showing that adults can influence food allocation and competition among nestlings
      by coordinating their feeding visits. Our results confirm the hypothesis that the
      monopolizability of food affects the intensity of sibling competition, and
      highlight the importance of understanding the temporal strategies of food
      delivery.

PMID- 20053664
TI  - Suppression of Ca2+ signaling in a mouse model of Best disease.
AB  - Mutations in BEST1, encoding bestrophin-1 (Best1), cause Best vitelliform macular
      dystrophy (BVMD), a dominantly inherited macular degeneration characterized by a
      diminished electrooculogram light peak (LP), lipofuscin in retinal pigment
      epithelial cells (RPE), and fluid- and debris-filled retinal detachments. To
      understand the pathogenesis of BVMD we generated knock-in mice carrying the BVMD
      causing mutation W93C in Best1. Both Best1(+/W93C)and Best1(W93C/W93C) mice had
      normal ERG a- and b-waves, but exhibited an altered LP luminance response
      reminiscent of that observed in BVMD patients. Morphological analysis identified
      fluid- and debris-filled retinal detachments in mice as young as 6 months of age.
      By 18-24 months of age Best1(+/W93C)and Best1(W93C/W93C) mice exhibited enhanced
      accumulation of lipofuscin in the RPE, and a significant deposition of debris
      composed of unphagocytosed photoreceptor outer segments and lipofuscin granules
      in the subretinal space. Although Best1 is thought to function as a Ca(2+)
      activated Cl(-) channel, RPE cells from Best1(W93C) mice exhibited normal Cl(-)
      conductances. We have previously shown that Best1(-/-) mice exhibit increased
      [Ca(2+)](i) in response to ATP stimulation. However, ATP-stimulated changes in
      [Ca(2+)](i) in RPE cells from Best1(+/W93C) and Best1(W93C/W93C) mice were
      suppressed relative to Best1(+/+) littermates. Based on these data we conclude
      that mice carrying the Best1(W93C) mutation are a valid model for BVMD.
      Furthermore, these data suggest that BVMD is not because of Best1 deficiency, as
      the phenotypes of Best1(+/W93C) and Best1(W93C/W93C) mice are distinct from that
      of Best1(-/-) mice with regard to lipofuscin accumulation, and changes in the LP
      and ATP Ca(2+) responses.

PMID- 20053665
TI  - Pkd1 transgenic mice: adult model of polycystic kidney disease with extrarenal
      and renal phenotypes.
AB  - While high levels of Pkd1 expression are detected in tissues of patients with
      autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether
      enhanced expression could be a pathogenetic mechanism for this systemic disorder.
      Three transgenic mouse lines were generated from a Pkd1-BAC modified by
      introducing a silent tag via homologous recombination to target a sustained wild
      type genomic Pkd1 expression within the native tissue and temporal regulation.
      These mice specifically overexpressed the Pkd1 transgene in extrarenal and renal
      tissues from approximately 2- to 15-fold over Pkd1 endogenous levels in a copy
      dependent manner. All transgenic mice reproducibly developed tubular and
      glomerular cysts leading to renal insufficiency. Interestingly, Pkd1(TAG) mice
      also exhibited renal fibrosis and calcium deposits in papilla reminiscent of
      nephrolithiasis as frequently observed in ADPKD. Similar to human ADPKD, these
      mice consistently displayed hepatic fibrosis and approximately 15% intrahepatic
      cysts of the bile ducts affecting females preferentially. Moreover, a significant
      proportion of mice developed cardiac anomalies with severe left-ventricular
      hypertrophy, marked aortic arch distention and/or valvular stenosis and
      calcification that had profound functional impact. Of significance, Pkd1(TAG)
      mice displayed occasional cerebral lesions with evidence of ruptured and
      unruptured cerebral aneurysms. This Pkd1(TAG) mouse model demonstrates that
      overexpression of wild-type Pkd1 can trigger the typical adult renal and
      extrarenal phenotypes resembling human ADPKD.

PMID- 20053666
TI  - Mechanisms of mosaicism, chimerism and uniparental disomy identified by single
      nucleotide polymorphism array analysis.
AB  - Mosaic aneuploidy and uniparental disomy (UPD) arise from mitotic or meiotic
      events. There are differences between these mechanisms in terms of (i) impact on
      embryonic development; (ii) co-occurrence of mosaic trisomy and UPD and (iii)
      potential recurrence risks. We used a genome-wide single nucleotide polymorphism
      (SNP) array to study patients with chromosome aneuploidy mosaicism, UPD and one
      individual with XX/XY chimerism to gain insight into the developmental mechanism
      and timing of these events. Sixteen cases of mosaic aneuploidy originated
      mitotically, and these included four rare trisomies and all of the monosomies,
      consistent with the influence of selective factors. Five trisomies arose
      meiotically, and three of the five had UPD in the disomic cells, confirming
      increased risk for UPD in the case of meiotic non-disjunction. Evidence for the
      meiotic origin of aneuploidy and UPD was seen in the patterns of recombination
      visible during analysis with 1-3 crossovers per chromosome. The mechanisms of
      formation of the UPD included trisomy rescue, with and without concomitant
      trisomy, monosomy rescue, and mitotic formation of a mosaic segmental UPD. UPD
      was also identified in an XX/XY chimeric individual, with one cell line having
      complete maternal UPD consistent with a parthenogenetic origin. Utilization of
      SNP arrays allows simultaneous evaluation of genomic alterations and insights
      into aneuploidy and UPD mechanisms. Differentiation of mitotic and meiotic
      origins for aneuploidy and UPD supports existence of selective factors against
      full trisomy of some chromosomes in the early embryo and provides data for
      estimation of recurrence and disease mechanisms.

PMID- 20053667
TI  - Molecular control of the cytosolic aconitase/IRP1 switch by extramitochondrial
      frataxin.
AB  - The inability to produce normal levels of the mitochondrial protein frataxin
      causes the hereditary degenerative disorder Friedreich's Ataxia (FRDA), a
      syndrome characterized by progressive gait instability, cardiomyopathy and high
      incidence of diabetes. Frataxin is an iron-binding protein involved in the
      biogenesis of iron-sulfur clusters (ISC), prosthetic groups allowing essential
      cellular functions such as oxidative phosphorylation, enzyme catalysis and gene
      regulation. Although several evidence suggest that frataxin acts as an iron
      chaperone within the mitochondrial compartment, we have recently demonstrated the
      existence of a functional extramitochondrial pool of mature frataxin in various
      human cell types. Here, we show that a similar proteolytic process generates both
      mature mitochondrial and extramitochondrial frataxin. To address the
      physiological function of human extramitochondrial frataxin, we searched for ISC
      dependent interaction partners. We demonstrate that the extramitochondrial form
      of frataxin directly interacts with cytosolic aconitase/iron regulatory protein-1
      (IRP1), a bifunctional protein alternating between an enzymatic and a RNA-binding
      function through the 'iron-sulfur switch' mechanism. Importantly, we found that
      the cytosolic aconitase defect and consequent IRP1 activation occurring in FRDA
      cells are reversed by the action of extramitochondrial frataxin. These results
      provide new insight into the control of cytosolic aconitase/IRP1 switch and
      expand current knowledge about the molecular pathogenesis of FRDA.

PMID- 20053668
TI  - Gain-of-function mutation in FGFR3 in mice leads to decreased bone mass by
      affecting both osteoblastogenesis and osteoclastogenesis.
AB  - Achondroplasia (ACH) is a short-limbed dwarfism resulting from gain-of-function
      mutations in fibroblast growth factor receptor 3 (FGFR3). Previous studies have
      shown that ACH patients have impaired chondrogenesis, but the effects of FGFR3 on
      bone formation and bone remodeling at adult stages of ACH have not been fully
      investigated. Using micro-computed tomography and histomorphometric analyses, we
      found that 2-month-old Fgfr3(G369C/+) mice (mouse model mimicking human ACH)
      showed decreased bone mass due to reduced trabecular bone volume and bone mineral
      density, defect in bone mineralization and increased osteoclast numbers and
      activity. Compared with primary cultures of bone marrow stromal cells (BMSCs)
      from wild-type mice, Fgfr3(G369C/+) cultures showed decreased cell proliferation,
      increased osteogenic differentiation including up-regulation of alkaline
      phosphatase activity and expressions of osteoblast marker genes, and reduced bone
      matrix mineralization. Furthermore, our studies also suggest that decreased cell
      proliferation and enhanced osteogenic differentiation observed in Fgfr3(G369C/+)
      BMSCs are caused by up-regulation of p38 phosphorylation and that enhanced Erk1/2
      activity is responsible for the impaired bone matrix mineralization. In addition,
      in vitro osteoclast formation and bone resorption assays demonstrated that
      osteoclast numbers and bone resorption area were increased in cultured bone
      marrow cells derived from Fgfr3(G369C/+) mice. These findings demonstrate that
      gain-of-function mutation in FGFR3 leads to decreased bone mass by regulating
      both osteoblast and osteoclast activities. Our studies provide new insight into
      the mechanism underlying the development of ACH.

PMID- 20053669
TI  - Role of Magmas in protein transport and human mitochondria biogenesis.
AB  - Magmas, a conserved mammalian protein essential for eukaryotic development, is
      overexpressed in prostate carcinomas and cells exposed to granulocyte-macrophage
      colony-stimulating factor (GM-CSF). Reduced Magmas expression resulted in
      decreased proliferative rates in cultured cells. However, the cellular function
      of Magmas is still elusive. In this report, we have showed that human Magmas is
      an ortholog of Saccharomyces cerevisiae Pam16 having similar functions and is
      critical for protein translocation across mitochondrial inner membrane. Human
      Magmas shows a complete growth complementation of Deltapam16 yeast cells at all
      temperatures. On the basis of our analysis, we report that Magmas localizes into
      mitochondria and is peripherally associated with inner mitochondrial membrane in
      yeast and humans. Magmas forms a stable subcomplex with J-protein Pam18 or
      DnaJC19 through its C-terminal region and is tethered to TIM23 complex of yeast
      and humans. Importantly, amino acid alterations in Magmas leads to reduced
      stability of the subcomplex with Pam18 that results in temperature sensitivity
      and in vivo protein translocation defects in yeast cells. These observations
      highlight the central role of Magmas in protein import and mitochondria
      biogenesis. In humans, absence of a functional DnaJC19 leads to dilated cardiac
      myophathic syndrome (DCM), a genetic disorder with characteristic features of
      cardiac myophathy and neurodegeneration. We propose that the mutations resulting
      in decreased stability of functional Magmas:DnaJC19 subcomplex at human TIM23
      channel leads to impaired protein import and cellular respiration in DCM
      patients. Together, we propose a model showing how Magmas:DnaJC19 subcomplex is
      associated with TIM23 complex and thus regulates mitochondrial import process.

PMID- 20053670
TI  - The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal
      muscles of transgenic mice and interacts with eEF1A2.
AB  - The molecular mechanisms regulating expression of utrophin A are of therapeutic
      interest since upregulating its expression at the sarcolemma can compensate for
      the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The
      5'-UTR of utrophin A has been previously shown to drive cap-independent internal
      ribosome entry site (IRES)-mediated translation in response to muscle
      regeneration and glucocorticoid treatment. To determine whether the utrophin A
      IRES displays tissue specific activity, we generated transgenic mice harboring
      control (CMV/betaGAL/CAT) or utrophin A 5'-UTR (CMV/betaGAL/UtrA/CAT) bicistronic
      reporter transgenes. Examination of multiple tissues from two
      CMV/betaGAL/UtrA/CAT lines revealed that the utrophin A 5'-UTR drives cap
      independent translation of the reporter gene exclusively in skeletal muscles and
      no other examined tissues. This expression pattern suggested that skeletal muscle
      specific factors are involved in IRES-mediated translation of utrophin A. We
      performed RNA-affinity chromatography experiments combined with mass spectrometry
      to identify trans-factors that bind the utrophin A 5'-UTR and identified
      eukaryotic elongation factor 1A2 (eEF1A2). UV-crosslinking experiments confirmed
      the specificity of this interaction. Regions of the utrophin A 5'-UTR that bound
      eEF1A2 also mediated cap-independent translation in C2C12 muscle cells. Cultured
      cells lacking eEF1A2 had reduced IRES activity compared with cells overexpressing
      eEF1A2. Together, these results suggest an important role for eEF1A2 in driving
      cap-independent translation of utrophin A in skeletal muscle. The trans-factors
      and signaling pathways driving skeletal-muscle specific IRES-mediated translation
      of utrophin A could provide unique targets for developing pharmacological-based
      DMD therapies.

PMID- 20053671
TI  - The snoRNA MBII-52 (SNORD 115) is processed into smaller RNAs and regulates
      alternative splicing.
AB  - The loss of HBII-52 and related C/D box small nucleolar RNA (snoRNA) expression
      units have been implicated as a cause for the Prader-Willi syndrome (PWS). We
      recently found that the C/D box snoRNA HBII-52 changes the alternative splicing
      of the serotonin receptor 2C pre-mRNA, which is different from the traditional
      C/D box snoRNA function in non-mRNA methylation. Using bioinformatic predictions
      and experimental verification, we identified five pre-mRNAs (DPM2, TAF1, RALGPS1,
      PBRM1 and CRHR1) containing alternative exons that are regulated by MBII-52, the
      mouse homolog of HBII-52. Analysis of a single member of the MBII-52 cluster of
      snoRNAs by RNase protection and northern blot analysis shows that the MBII-52
      expressing unit generates shorter RNAs that originate from the full-length MBII
      52 snoRNA through additional processing steps. These novel RNAs associate with
      hnRNPs and not with proteins associated with canonical C/D box snoRNAs. Our data
      indicate that not a traditional C/D box snoRNA MBII-52, but a processed version
      lacking the snoRNA stem is the predominant MBII-52 RNA missing in PWS. This
      processed snoRNA functions in alternative splice-site selection. Its substitution
      could be a therapeutic principle for PWS.

PMID- 20053672
TI  - Prevention and treatment of microvascular disease in childhood type 1 diabetes.
AB  - INTRODUCTION: The incidence of type 1 diabetes (T1D) is increasing worldwide,
      particularly in children, and is associated with a significant burden, mainly
      related to the development of vascular complications. The prevention and
      treatment of microvascular complications, which include nephropathy, retinopathy
      and neuropathy, are of paramount importance to decrease the associated mortality
      and morbidity. SOURCES OF DATA: A literature search was performed on Medline and
      articles on microvascular complications, with particular emphasis on the
      increasing incidence of childhood T1D and its implications on prevention and
      treatment of complications, were selected. AREAS OF AGREEMENT: The incidence of
      childhood T1D is increasing. Early identification of subjects at risk for long
      term complications and early implementation of preventive and therapeutic
      strategies are fundamental in order to reduce the burden associated with
      microvascular complications of diabetes. Improving glycaemic control is the
      principle way of preventing and treating T1D complications. AREAS OF CONTROVERSY:
      In adults with T1D and microvascular complications, treatment with anti
      hypertensive drugs and statins is increasingly common, whereas there are no
      definitive indications for treatment with these drugs in children and adolescents
      with early signs of complications. GROWING POINTS: There is growing interest in
      the development of new preventive and therapeutic strategies targeting specific
      pathways implicated in the pathogenesis of microvascular complications. AREAS
      TIMELY FOR DEVELOPING RESEARCH: Investigations to clarify genetic and
      environmental factors implicated in the pathogenesis of microvascular
      complications could lead to the identification of biochemical markers with high
      predictive values, to be used as a guide for screening and intervention
      programmes.

PMID- 20053673
TI  - Effectiveness of a geriatric intervention in primary care: a randomized clinical
      trial.
AB  - OBJECTIVE: To assess the effectiveness of an intervention after comprehensive
      geriatric assessment (CGA) in reducing morbidity and mortality in patients over
      74 years in primary care. METHODS: Randomized controlled trial with 18 months of
      follow-up. Patients in the control group (CG) followed usual care. Patients in
      the intervention group (IG) were classified as at risk or non-risk of frailty
      based on the CGA. Patients at non-risk of frailty in the IG were provided with
      recommendations about healthy habits and adherence to treatment in group
      sessions, while patients at risk of frailty were visited individually by a
      geriatrician. RESULTS: Six hundred and twenty patients were randomized to the IG
      (49.7%) or to the CG (50.3%), 83.2% completed follow-up. Cox's proportional
      hazards model showed as covariates the study group (hazard ratio [HR] 0.58; 95%
      confidence interval [CI] 0.28-1.22), risk of frailty (HR 1.33; 95% CI 0.71-2.51)
      and the interaction between both (HR 3.08; 95% CI 1.22-7.78). Forty-nine percent
      of the patients in the IG and 43% in the CG were at risk of frailty at baseline.
      At the end of the study, 27.9% of the IG and 13.5% of the CG had reversed their
      initial at risk of frailty status (P = 0.027). Multivariate predictors of
      reversible risk of frailty were younger age, not being at risk of depression, low
      consumption of medications and the intervention itself. CONCLUSIONS: A specific
      intervention in patients over 74 years attended in primary care reduces morbidity
      and mortality in patients at risk of frailty and increases the proportion of
      patients that reversed their initial status at risk of frailty.

PMID- 20053674
TI  - The relationship between continuity and patient satisfaction: a systematic
      review.
AB  - BACKGROUND: Continuity between doctors and patients likely affects patient
      satisfaction. OBJECTIVE: To assess the current evidence on the relationship
      between continuity and patient satisfaction. METHODS: Systematic review of
      studies of adults in general, family, or internal medicine practices with
      ongoing, direct, face-to-face contact with their physician. Measures of the
      relationship between continuity and patient satisfaction were examined. RESULTS:
      A MEDLINE search covering 1984-2007 and a Cumulative Index to Nursing and Allied
      Health Literature search covering 1981-2007 identified 263 relevant studies and
      12 studies met inclusion criteria. There were 12 different continuity measures
      and 9 different satisfaction measures. CONCLUSIONS: Continuity has a variable
      effect on patient satisfaction.

PMID- 20053675
TI  - Intracellular targeting signals and lipid specificity determinants of the
      ALA/ALIS P4-ATPase complex reside in the catalytic ALA alpha-subunit.
AB  - Members of the P(4) subfamily of P-type ATPases are believed to catalyze flipping
      of phospholipids across cellular membranes, in this way contributing to vesicle
      biogenesis in the secretory and endocytic pathways. P(4)-ATPases form heteromeric
      complexes with Cdc50-like proteins, and it has been suggested that these act as
      beta-subunits in the P(4)-ATPase transport machinery. In this work, we
      investigated the role of Cdc50-like beta-subunits of P(4)-ATPases for targeting
      and function of P(4)-ATPase catalytic alpha-subunits. We show that the
      Arabidopsis P(4)-ATPases ALA2 and ALA3 gain functionality when coexpressed with
      any of three different ALIS Cdc50-like beta-subunits. However, the final cellular
      destination of P(4)-ATPases as well as their lipid substrate specificity are
      independent of the nature of the ALIS beta-subunit they were allowed to interact
      with.

PMID- 20053676
TI  - Global up-regulation of microtubule dynamics and polarity reversal during
      regeneration of an axon from a dendrite.
AB  - Axon regeneration is crucial for recovery after trauma to the nervous system. For
      neurons to recover from complete axon removal they must respecify a dendrite as
      an axon: a complete reversal of polarity. We show that Drosophila neurons in vivo
      can convert a dendrite to a regenerating axon and that this process involves
      rebuilding the entire neuronal microtubule cytoskeleton. Two major microtubule
      rearrangements are specifically induced by axon and not dendrite removal: 1) 10
      fold up-regulation of the number of growing microtubules and 2) microtubule
      polarity reversal. After one dendrite reverses its microtubules, it initiates tip
      growth and takes on morphological and molecular characteristics of an axon. Only
      neurons with a single dendrite that reverses polarity are able to initiate tip
      growth, and normal microtubule plus-end dynamics are required to initiate this
      growth. In addition, we find that JNK signaling is required for both the up
      regulation of microtubule dynamics and microtubule polarity reversal initiated by
      axon injury. We conclude that regulation of microtubule dynamics and polarity in
      response to JNK signaling is key to initiating regeneration of an axon from a
      dendrite.

PMID- 20053677
TI  - Numb independently antagonizes Sanpodo membrane targeting and Notch signaling in
      Drosophila sensory organ precursor cells.
AB  - In Drosophila, mitotic neural progenitor cells asymmetrically segregate the cell
      fate determinant Numb in order to block Notch signaling in only one of the two
      daughter cells. Sanpodo, a membrane protein required for Notch signaling in
      asymmetrically dividing cells, is sequestered from the plasma membrane to
      intracellular vesicles in a Numb-dependent way after neural progenitor cell
      mitosis. However, the significance of Numb-dependent Sanpodo regulation is
      unclear. In this study, we conducted a structure-function analysis to identify
      the determinants of Sanpodo targeting in vivo. We identified an NPAF motif in the
      amino-terminal cytoplasmic tail of Sanpodo, which is conserved among insect
      Sanpodo homologues. The Sanpodo NPAF motif is predicted to bind directly to the
      Numb phosphotyrosine-binding domain and is critical for Numb binding in vitro.
      Deletion or mutation of the NPAF motif results in accumulation of Sanpodo at the
      plasma membrane in Numb-positive cells in vivo. Genetic analysis of Sanpodo NPAF
      mutants shows that Numb-dependent Sanpodo endocytic targeting can be uncoupled
      from Notch signaling regulation. Our findings demonstrate that Sanpodo contains
      an evolutionarily conserved motif that has been linked to Numb-dependent
      regulation in vertebrates and further support the model that Numb regulates Notch
      signaling independently of Sanpodo membrane trafficking in neural progenitor
      cells.

PMID- 20053678
TI  - NPP-16/Nup50 function and CDK-1 inactivation are associated with anoxia-induced
      prophase arrest in Caenorhabditis elegans.
AB  - Oxygen, an essential nutrient, is sensed by a multiple of cellular pathways that
      facilitate the responses to and survival of oxygen deprivation. The
      Caenorhabditis elegans embryo exposed to severe oxygen deprivation (anoxia)
      enters a state of suspended animation in which cell cycle progression reversibly
      arrests at specific stages. The mechanisms regulating interphase, prophase, or
      metaphase arrest in response to anoxia are not completely understood.
      Characteristics of arrested prophase blastomeres and oocytes are the alignment of
      condensed chromosomes at the nuclear periphery and an arrest of nuclear envelope
      breakdown. Notably, anoxia-induced prophase arrest is suppressed in mutant
      embryos lacking nucleoporin NPP-16/NUP50 function, indicating that this
      nucleoporin plays an important role in prophase arrest in wild-type embryos.
      Although the inactive form of cyclin-dependent kinase (CDK-1) is detected in wild
      type-arrested prophase blastomeres, the inactive state is not detected in the
      anoxia exposed npp-16 mutant. Furthermore, we found that CDK-1 localizes near
      chromosomes in anoxia-exposed embryos. These data support the notion that NPP-16
      and CDK-1 function to arrest prophase blastomeres in C. elegans embryos. The
      anoxia-induced shift of cells from an actively dividing state to an arrested
      state reveals a previously uncharacterized prophase checkpoint in the C. elegans
      embryo.

PMID- 20053680
TI  - Essential role of the p110beta subunit of phosphoinositide 3-OH kinase in male
      fertility.
AB  - Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility.
      However, the specific roles of different p110 PI3K catalytic subunits within the
      spermatogenic lineage have not been characterized so far. Herein, we report that
      male mice expressing a catalytically inactive p110beta develop testicular
      hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo
      azoospermia and defective fertility. The examination of testes from p110beta
      defective tubules demonstrates a widespread loss in spermatogenic cells, due to
      defective proliferation and survival of pre- and postmeiotic cells. In
      particular, p110beta is crucially needed in c-Kit-mediated spermatogonial
      expansion, as c-Kit-positive cells are lost in the adult testis and activation of
      Akt by SCF is blocked by a p110beta inhibitor. These data establish that
      activation of the p110beta PI3K isoform by c-Kit is required during
      spermatogenesis, thus opening the way to new treatments for c-Kit positive
      testicular cancers.

PMID- 20053679
TI  - The late endosome is essential for mTORC1 signaling.
AB  - The multisubunit mTORC1 complex integrates signals from growth factors and
      nutrients to regulate protein synthesis, cell growth, and autophagy. To examine
      how endocytic trafficking might be involved in nutrient regulation of mTORC1, we
      perturbed specific endocytic trafficking pathways and measured mTORC1 activity
      using S6K1 as a readout. When early/late endosomal conversion was blocked by
      either overexpression of constitutively active Rab5 (Rab5CA) or knockdown of the
      Rab7 GEF hVps39, insulin- and amino acid-stimulated mTORC1/S6K1 activation were
      inhibited, and mTOR localized to hybrid early/late endosomes. Inhibition of other
      stages of endocytic trafficking had no effect on mTORC1. Overexpression of Rheb,
      which activates mTOR independently of mTOR localization, rescued mTORC1 signaling
      in cells expressing Rab5CA, whereas hyperactivation of endogenous Rheb in TSC2-/-
      MEFs did not. These data suggest that integrity of late endosomes is essential
      for amino acid- and insulin-stimulated mTORC1 signaling and that blocking the
      early/late endosomal conversion prevents mTOR from interacting with Rheb in the
      late endosomal compartment.

PMID- 20053681
TI  - Enhanced H2AX phosphorylation, DNA replication fork arrest, and cell death in the
      absence of Chk1.
AB  - H2AX phosphorylation at serine 139 (gammaH2AX) is a sensitive indicator of both
      DNA damage and DNA replication stress. Here we show that gammaH2AX formation is
      greatly enhanced in response to replication inhibitors but not ionizing radiation
      in HCT116 or SW480 cells depleted of Chk1. Although H2AX phosphorylation precedes
      the induction of apoptosis in such cells, our results suggest that cells
      containing gammaH2AX are not committed to death. gammaH2AX foci in these cells
      largely colocalize with RPA foci and their formation is dependent upon the
      essential replication helicase cofactor Cdc45, suggesting that H2AX
      phosphorylation occurs at sites of stalled forks. However Chk1-depleted cells
      released from replication inhibitors retain gammaH2AX foci and do not appear to
      resume replicative DNA synthesis. BrdU incorporation only occurs in a minority of
      Chk1-depleted cells containing gammaH2AX foci after release from thymidine arrest
      and, in cells incorporating BrdU, DNA synthesis does not occur at sites of
      gammaH2AX foci. Furthermore activated ATM and Chk2 persist in these cells. We
      propose that the gammaH2AX foci in Chk1-depleted cells may represent sites of
      persistent replication fork damage or abandonment that are unable to resume DNA
      synthesis but do not play a direct role in the Chk1 suppressed death pathway.

PMID- 20053682
TI  - Structural mutants of the spindle pole body cause distinct alteration of
      cytoplasmic microtubules and nuclear dynamics in multinucleated hyphae.
AB  - In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs)
      emerge from the spindle pole body outer plaque (OP) in perpendicular and
      tangential directions. To elucidate the role of cMTs in forward/backward
      movements (oscillations) and bypassing of nuclei, we constructed mutants
      potentially affecting cMT nucleation or stability. Hyphae lacking the OP
      components AgSpc72, AgNud1, AgCnm67, or the microtubule-stabilizing factor AgStu2
      grew like wild- type but showed substantial alterations in the number, length,
      and/or nucleation sites of cMTs. These mutants differently influenced nuclear
      oscillation and bypassing. In Agspc72Delta, only long cMTs were observed, which
      emanate tangentially from reduced OPs; nuclei mainly moved with the cytoplasmic
      stream but some performed rapid bypassing. Agnud1Delta and Agcnm67Delta lack OPs;
      short and long cMTs emerged from the spindle pole body bridge/half-bridge
      structures, explaining nuclear oscillation and bypassing in these mutants. In
      Agstu2Delta only very short cMTs emanated from structurally intact OPs; all
      nuclei moved with the cytoplasmic stream. Therefore, long tangential cMTs promote
      nuclear bypassing and short cMTs are important for nuclear oscillation. Our
      electron microscopy ultrastructural analysis also indicated that assembly of the
      OP occurs in a stepwise manner, starting with AgCnm67, followed by AgNud1 and
      lastly AgSpc72.

PMID- 20053683
TI  - Nuclear translocation of beta-actin is involved in transcriptional regulation
      during macrophage differentiation of HL-60 cells.
AB  - Studies have shown that nuclear translocation of actin occurs under certain
      conditions of cellular stress; however, the functional significance of actin
      import remains unclear. Here, we demonstrate that during the phorbol 12-myristate
      13-acetate (PMA)-induced differentiation of HL-60 cells toward macrophages, beta
      actin translocates from the cytoplasm to the nucleus and that this process is
      dramatically inhibited by pretreatment with p38 mitogen-activated protein kinase
      inhibitors. Using chromatin immunoprecipitation-on-chip assays, the genome-wide
      maps of beta-actin binding to gene promoters in response to PMA treatment is
      analyzed in HL-60 cells. A gene ontology-based analysis shows that the identified
      genes belong to a broad spectrum of functional categories such as cell growth and
      differentiation, signal transduction, response to external stimulus, ion channel
      activity, and immune response. We also demonstrate a correlation between beta
      actin occupancy and the recruitment of RNA polymerase II at six selected target
      genes, and beta-actin knockdown decreases the mRNA expression levels of these
      target genes induced by PMA. We further show that nuclear beta-actin is required
      for PMA-induced transactivation of one target gene, solute carrier family 11
      member 1, which is important for macrophage activation. Our data provide novel
      evidence that nuclear accumulation of beta-actin is involved in transcriptional
      regulation during macrophage-like differentiation of HL-60 cells.

PMID- 20053684
TI  - Distinct and temporal roles of nucleosomal remodeling and histone deacetylation
      in the repression of the hTERT gene.
AB  - hTERT, the human telomerase reverse transcriptase, is highly expressed in stem
      cells and embryonic tissues but undetectable in most adult somatic cells. To
      understand its repression mechanisms in somatic cells, we investigated the
      endogenous hTERT gene regulation during differentiation of human leukemic HL60
      cells. Our study revealed that silencing of the hTERT promoter was a biphasic
      process. Within 24 h after initiation of differentiation, hTERT mRNA expression
      decreased dramatically, accompanied by increased expression of Mad1 gene and
      disappearance of a nucleosome-free region at the hTERT core promoter. Subsequent
      to this early repression, nucleosomal remodeling continued at the promoter and
      downstream region for several days, as demonstrated by micrococcal nuclease and
      restriction enzyme accessibility assays. This later nucleosomal remodeling
      correlated with stable silencing of the hTERT promoter. Progressive changes of
      core histone modifications occurred throughout the entire differentiation
      process. Surprisingly, inhibition of histone deacetylation at the hTERT promoter
      did not prevent hTERT repression or nucleosomal deposition, indicating that
      nucleosomal deposition at the core promoter, but not histone deacetylation, was
      the cause of transcriptional repression. Our data also suggested that succeeding
      nucleosomal remodeling and histone deacetylation worked in parallel to establish
      the stable repressive status of hTERT gene in human somatic cells.

PMID- 20053685
TI  - Fate specification and tissue-specific cell cycle control of the Caenorhabditis
      elegans intestine.
AB  - Coordination between cell fate specification and cell cycle control in
      multicellular organisms is essential to regulate cell numbers in tissues and
      organs during development, and its failure may lead to oncogenesis. In mammalian
      cells, as part of a general cell cycle checkpoint mechanism, the F-box protein
      beta-transducin repeat-containing protein (beta-TrCP) and the Skp1/Cul1/F-box
      complex control the periodic cell cycle fluctuations in abundance of the CDC25A
      and B phosphatases. Here, we find that the Caenorhabditis elegans beta-TrCP
      orthologue LIN-23 regulates a progressive decline of CDC-25.1 abundance over
      several embryonic cell cycles and specifies cell number of one tissue, the
      embryonic intestine. The negative regulation of CDC-25.1 abundance by LIN-23 may
      be developmentally controlled because CDC-25.1 accumulates over time within the
      developing germline, where LIN-23 is also present. Concurrent with the
      destabilization of CDC-25.1, LIN-23 displays a spatially dynamic behavior in the
      embryo, periodically entering a nuclear compartment where CDC-25.1 is abundant.

PMID- 20053686
TI  - Son is essential for nuclear speckle organization and cell cycle progression.
AB  - Subnuclear organization and spatiotemporal regulation of pre-mRNA processing
      factors is essential for the production of mature protein-coding mRNAs. We have
      discovered that a large protein called Son has a novel role in maintaining proper
      nuclear organization of pre-mRNA processing factors in nuclear speckles. The
      primary sequence of Son contains a concentrated region of multiple unique tandem
      repeat motifs that may support a role for Son as a scaffolding protein for RNA
      processing factors in nuclear speckles. We used RNA interference (RNAi)
      approaches and high-resolution microscopy techniques to study the functions of
      Son in the context of intact cells. Although Son precisely colocalizes with pre
      mRNA splicing factors in nuclear speckles, its depletion by RNAi leads to cell
      cycle arrest in metaphase and causes dramatic disorganization of small nuclear
      ribonuclear protein and serine-arginine rich protein splicing factors during
      interphase. Here, we propose that Son is essential for appropriate subnuclear
      organization of pre-mRNA splicing factors and for promoting normal cell cycle
      progression.

PMID- 20053688
TI  - High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium
      falciparum isolates in pregnant women at the time of introduction of intermittent
      preventive treatment with sulfadoxine/pyrimethamine in Gabon.
AB  - OBJECTIVES: The frequency of dhfr and dhps point mutations was assessed in
      Plasmodium falciparum isolates from pregnant women in Libreville. METHODS: PCR
      restriction fragment length polymorphism of polymorphic codons of the dhfr gene
      (51, 59 and 108) and the dhps gene (436, 437 and 540) was performed in matched
      peripheral and placental blood samples. RESULTS: The proportion of multiple
      mutations was high (98%), and was not different between women with and without a
      history of intermittent preventive treatment with sulfadoxine/pyrimethamine
      (IPTp/SP). The prevalence of triple dhfr mutation was 80%, and that of quadruple
      and quintuple mutations was 53% and 22%, respectively. The Glu540 mutation was
      present in two isolates. The concordance of resistant alleles in matched
      peripheral and placental isolates was >90% for both genes. CONCLUSIONS: These
      findings underline the need for a regular assessment of the relationship between
      the presence of resistant isolates and in vitro/in vivo IPTp/SP efficacy, and
      evaluation of an alternative drug.

PMID- 20053687
TI  - Glycolipid trafficking in Drosophila undergoes pathway switching in response to
      aberrant cholesterol levels.
AB  - In lipid storage diseases, the intracellular trafficking of sphingolipids is
      altered by conditions of aberrant cholesterol accumulation. Drosophila has been
      used recently to model lipid storage diseases, but the effects of sterol
      accumulation on sphingolipid trafficking are not known in the fly, and the
      trafficking of sphingolipids in general has not been studied in this model
      organism. Here, we examined the uptake and intracellular distribution of a
      fluorescent glycolipid analog, BODIPY-lactosyl-ceramide, in Drosophila neurons.
      The uptake mechanism and intracellular trafficking route of this simple
      glycolipid are largely conserved. Our principle finding is that cholesterol
      steers trafficking of the glycolipid between Golgi, lysosome, and recycling
      compartments. Our analyses support the idea that cholesterol storage in
      Drosophila triggers a switch in glycolipid trafficking from the biosynthetic to
      the degradative endolysosomal pathway, whereas cholesterol depletion eliminates
      recycling of the glycolipid. Unexpectedly, we observe a novel phenomenon we term
      "hijacking," whereby lactosyl-ceramide diverts the trafficking pathway of an
      endocytic cargo, dextran, completely away from its lysosomal target. This work
      establishes that glycolipid trafficking in Drosophila undergoes changes similar
      to those seen in mammalian cells under conditions of cholesterol storage and
      therefore validates Drosophila as a suitable model organism in which to study
      lipid storage diseases.

PMID- 20053689
TI  - N-chlorotaurine, a natural antiseptic with outstanding tolerability.
AB  - N-chlorotaurine, the N-chloro derivative of the amino acid taurine, is a long
      lived oxidant produced by activated human granulocytes and monocytes. Supported
      by a high number of in vitro studies, it has mainly anti-inflammatory properties
      and seems to be involved in the termination of inflammation. The successful
      synthesis of the crystalline sodium salt (Cl-HN-CH(2)-CH(2)-SO(3)Na, NCT)
      facilitated its development as an endogenous antiseptic. NCT can be stored long
      term at low temperatures, and it has killing activity against bacteria, fungi,
      viruses and parasites. Transfer of the active chlorine to amino groups of
      molecules of both the pathogens and the human body (transhalogenation) enhances
      rather than decreases its activity, mainly because of the formation of
      monochloramine. Furthermore, surface chlorination after sublethal incubation
      times in NCT leads to a post-antibiotic effect and loss of virulence of
      pathogens, as demonstrated for bacteria and yeasts. Being a mild oxidant, NCT
      proved to be very well tolerated by human tissue in Phase I and II clinical
      studies. A 1% aqueous solution can be applied to the eye, skin ulcerations, outer
      ear canal, nasal and paranasal sinuses, oral cavity and urinary bladder, and can
      probably be used for inhalation. Therapeutic efficacy in Phase II studies has
      been shown in external otitis, purulently coated crural ulcerations and
      keratoconjunctivitis, so far. Based upon all presently available data, NCT seems
      to be an antiseptic with a very good relation between tolerability and activity.
      Recently, C-methylated derivatives of NCT have been invented, which are of
      interest because of improved stability at room temperature.

PMID- 20053691
TI  - CTX-M as the predominant extended-spectrum beta-lactamases among
      Enterobacteriaceae in Manila, Philippines.

PMID- 20053690
TI  - Molecular characterization of extended-spectrum beta-lactamases in clinical
      Escherichia coli and Klebsiella pneumoniae isolates from Surabaya, Indonesia.
AB  - BACKGROUND: No detailed reports regarding extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae are currently available from Indonesia, the fourth
      most populous country in the world. METHODS: A survey was carried out to
      investigate the molecular epidemiology and genetic characteristics of clinical
      ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates originating
      from the Dr. Soetomo Academic Hospital in Surabaya, Indonesia, over a 4 month
      period (January to April 2005). ESBLs were characterized by isoelectric focusing
      and PCR assays. Clonality of the isolates was assessed by PFGE and repetitive
      sequence-based PCR (rep-PCR). Phylogenetic grouping was performed among CTX-M-15
      producing E. coli. RESULTS: In total, 73 consecutive non-duplicate ESBL-positive
      E. coli and 72 K. pneumoniae strains were isolated. The bla(CTX-M-15) gene was
      found to be highly prevalent (69/73 strains, 94.5%) among the 73 ESBL-positive E.
      coli isolates. The gene was detected in both clonal and non-clonal isolates, as
      defined by PFGE and rep-PCR. Sixteen CTX-M-15-positive E. coli could be assigned
      to a single rep-PCR type and phylogenetic group B2 and belonged to the well-known
      O25b-ST131 clone. Among the 72 ESBL-positive K. pneumoniae isolates, bla(CTX-M
      15) was again the most prevalent ESBL (40/72, 55.6%). Several SHV-type enzymes
      were also frequently detected: SHV-5 (n = 28); SHV-12 (n = 13); and SHV-2 (n =
      6). TEM-type ESBLs were not detected in any of the isolates. CONCLUSIONS:
      Indonesia is another developing country affected by the emergence and spread of
      bacterial strains harbouring ESBL genes, including the CTX-M-15-producing B2-E.
      coli O25b-ST131 clone.

PMID- 20053694
TI  - Comment on: Antibiotic stewardship--more education and regulation not more
      availability?

PMID- 20053692
TI  - Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir
      disoproxil fumarate + emtricitabine promptly improves triglycerides and low
      density lipoprotein cholesterol in dyslipidaemic patients.
AB  - OBJECTIVES: To assess the impact of switching to tenofovir disoproxil fumarate +
      emtricitabine on lipid parameters. METHODS: HIV-infected patients with plasma
      viral load <400 copies/mL, fasted triglycerides from 2.3 to 11.4 mmol/L and/or
      fasted low-density lipoprotein (LDL)-cholesterol >4.1 mmol/L were randomized to
      switch the nucleoside reverse transcriptase inhibitor (NRTI) backbone to fixed
      dose combination tenofovir disoproxil fumarate + emtricitabine or to maintain the
      baseline antiretroviral regimen (the control group). The study has been
      registered with ClinicalTrials.gov under the identifier NCT00323492. RESULTS:
      Ninety-one patients were included in the intent-to-treat (ITT) analysis with
      triglycerides 2.4 mmol/L and LDL-cholesterol 4.0 mmol/L (median values). At week
      12, the median changes from baseline of triglycerides were -0.5 mmol/L (-25%; n =
      46) and -0.1 mmol/L (-6%; n = 45) in the tenofovir disoproxil fumarate +
      emtricitabine and control groups, respectively, indicating a difference of -0.4
      mmol/L (P = 0.034) [95% confidence interval (CI): -0.9 to -0.0]. Similarly for
      LDL-cholesterol, changes of -0.4 mmol/L (-9%) and -0.1 mmol/L (-1%) were observed
      in the tenofovir disoproxil fumarate + emtricitabine and control groups,
      respectively, indicating a difference of -0.4 mmol/L (P = 0.031) [95% CI: -0.7 to
      -0.0]. The proportion of patients with LDL-cholesterol >4.1 mmol/L decreased from
      48% at baseline to 26% at week 12 in the tenofovir disoproxil fumarate +
      emtricitabine group versus no change in the control group. No virological failure
      was observed during the study. CONCLUSIONS: Switching to tenofovir disoproxil
      fumarate + emtricitabine in dyslipidaemic HIV-infected patients improves
      triglycerides and LDL-cholesterol.

PMID- 20053693
TI  - Two-stage revision for prosthetic joint infection: predictors of outcome and the
      role of reimplantation microbiology.
AB  - OBJECTIVES: We describe rates of success for two-stage revision of prosthetic
      joint infection (PJI), including data on reimplantation microbiology. METHODS: We
      retrospectively collected data from all the cases of PJI that were managed with
      two-stage revision over a 4 year period. Patients were managed with an antibiotic
      free period before reimplantation, in order to confirm, clinically and
      microbiologically, that infection was successfully treated. RESULTS: One hundred
      and fifty-two cases were identified. The overall success rate (i.e. retention of
      the prosthesis over 5.75 years of follow-up) was 83%, but was 89% for first
      revisions and 73% for re-revisions [hazard ratio = 2.9, 95% confidence interval
      (CI) 1.2-7.4, P = 0.023]. Reimplantation microbiology was frequently positive
      (14%), but did not predict outcome (hazard ratio = 1.3, 95% CI 0.4-3.7, P = 0.6).
      Furthermore, most unplanned debridements following the first stage were carried
      out before antibiotics were stopped (25 versus 2 debridements). CONCLUSIONS: We
      did not identify evidence supporting the use of an antibiotic-free period before
      reimplantation and routine reimplantation microbiology. Re-revision was
      associated with a significantly worse outcome.

PMID- 20053695
TI  - Nationwide implementation of antibiotic management teams in Belgian hospitals: a
      self-reporting survey.
AB  - OBJECTIVES: Antibiotic management teams (AMTs) have been advocated to optimize
      the use of antimicrobials in hospitals. Since 2002, the Belgian Antibiotic Policy
      Coordination Committee (BAPCOC) has supported the development of AMTs in Belgian
      hospitals with policy guidance and federal funding for antibiotic managers. We
      performed a national, self-reporting survey to assess the level of AMT activities
      in 2007. METHODS: A structured questionnaire survey was performed on the
      composition, organization and service activities of the AMT in all acute care and
      larger chronic care hospitals in the country in 2007. Descriptive statistics were
      stratified by duration of AMT funding. RESULTS: Completed questionnaires were
      provided by 112 of 116 hospitals (response rate, 96.6%). Mutidisciplinary AMTs
      varied in size (mean 10, range 2-28 members). Antibiotic stewardship tools used
      by AMTs included: hospital antibiotic formulary (96.3% of hospitals); practice
      guidelines for antibiotic therapy and surgical prophylaxis (91.6% and 96.3%,
      respectively); list of 'restricted' antimicrobial agents (75.9%); concurrent
      review of antibiotic therapies (64.2%); de-escalation of therapy after a few days
      (63.9%); sequential intravenous/oral therapy for antibiotics with equivalent
      bioavailability (78.7%); dedicated antimicrobial order forms (36.1%); automatic
      stop of delivery (43.5%); analysis of antibiotic consumption data (96.2%); and
      analysis of microbial resistance data (89.8%). CONCLUSIONS: These data
      demonstrate a well-developed structure of AMTs in Belgian hospitals and the broad
      range of services provided. Technical and financial support by healthcare
      authorities was key to the extensive implementation of antimicrobial stewardship
      programmes across the national hospital care system.

PMID- 20053696
TI  - Surgical management of primary empyema of the pleural cavity: outcome of 81
      patients.
AB  - Postpneumonic empyema is the most common form of empyema thoracis and is still
      recognised as a major cause of morbidity and prolonged hospital stay. We reviewed
      106 patients retrospectively who underwent surgical management of pleural empyema
      over a period of three years from August 2005. We identified 81 patients (76%)
      (58 males, mean age 52 years) with primary empyema and 25 patients (24%) with
      secondary empyema. The first group of patients with primary empyema was analysed.
      Twenty-nine patients (36%) had stage II empyema and 52 patients (64%) had stage
      III. The majority of stage II empyema patients underwent thoracoscopic
      debridement (28 patients) and one patient had open thoracotomy and debridement.
      Stage III patients underwent thoracoscopic decortication (32 patients) of those
      six patients (19%) were converted to open decortication, open decortication (19
      patients) and fenestration (one patient). Mortality rate was 0% for all
      procedures. Median length of hospital stay was six days for thoracoscopic
      debridement, five days for thoracoscopic decortication and eight days for open
      decortication. Patients treated with video-assisted thoracoscopic surgery (VATS)
      debridement or decortication spent less time in hospital and the conversion rate
      to open procedure for stage III empyema was only 19%, which encourages us to
      consider VATS debridement/decortication as a first choice treatment.

PMID- 20053697
TI  - Multimodality treatment of malignant pleural mesothelioma with or without
      immunotherapy: does it change anything?
AB  - The purpose of this study was to investigate immunological effector cells and
      angiogenesis in malignant pleural mesothelioma (MPM) patients, who underwent
      multimodality treatments. Clinical and pathological characteristics of 57
      patients, with International Mesothelioma Interest Group stage II-III MPM, who
      underwent two different multimodality treatments (with and without immunotherapy)
      between 1999 and 2008 were analyzed. CD8+, CD4+ and Foxp3+ tumor-infiltrating
      lymphocytes, tryptase and chymase mast cells (MCs), CD34, number of microvessels
      and vascular endothelial growth factor were determined by immunohistochemistry.
      The histology was 51 epitheliomorf and 6 biphasic. The stage was III in 41 cases
      and II in 16 cases. With an average follow-up of 69 months (range 9-115) 14
      patients are still alive and the overall median actuarial survival is 21.4
      months. Tryptase MCs, CD8+ and Foxp3+ lymphocytes had significantly increased in
      the interleukin 2 (IL-2) treated group. Moreover, the number of microvessels was
      significantly lower in IL-2 treated patients. This study indicates that
      immunotherapy leads to an increase in cytotoxic CD8+ lymphocytes and tryptase MCs
      and to a decrease of the tumoral neoangiogenesis. Changes in MPM microenvironment
      induced by immunotherapy may play a major role in the local control of this
      disease and need further investigations.

PMID- 20053698
TI  - Occlusion of the right coronary artery ostium by an aortic cusp attachment.
AB  - Occlusion of the right coronary artery (RCA) ostium by an aortic cusp is a rare
      anomaly and can be a cause of sudden death. We report the case of a child with
      progressive stenosis of the right coronary ostium caused by a hypoplastic right
      coronary cusp that adhered to the aortic wall resulting in severe myocardial
      ischemia. The patient underwent a Ross-Konno operation with mitral valvuloplasty
      for congenital aortic valvular stenosis and mitral regurgitation caused by
      ischemia-induced posteromedial papillary muscle dysfunction. The myocardial
      ischemia was relieved by resection of the deformed pouch-like cusp to disclose
      the RCA ostium. Postoperative myocardial scintigraphy demonstrated no myocardial
      ischemia and multidetector computed tomography showed no coronary ostial
      stenosis.

PMID- 20053699
TI  - In hypoplastic left heart patients is Sano shunt compared with modified Blalock
      Taussig shunt associated with deleterious effects on ventricular performance?
AB  - A best evidence topic in congenital cardiac surgery was written according to a
      structured protocol. The question addressed was: in hypoplastic left heart
      patients is Sano shunt compared with modified Blalock-Taussig (mBT) shunt
      associated with deleterious effects on ventricular performance? Sano shunt
      modification of Norwood procedure involves construction of a right ventricle to
      pulmonary artery (RV-PA) conduit as an alternative source of pulmonary blood
      flow. Compared with the mBT shunt, the RV-PA conduit provides a more stable
      haemodynamic state in the immediate postoperative period and is reported to be
      associated with lower interstage mortality. However, concerns regarding the
      impact of ventriculotomy on short- and long-term performance of single ventricle
      have been expressed. Altogether 101 papers were found using the reported search
      terms, from 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.
      None of the echocardiographic or clinical outcome studies showed poor ventricular
      performance after ventriculotomy of the systemic RV for construction of Sano
      shunt. A small autopsy study of 11 patients showed greater remodelling of the
      ventricular myocardial extracellular matrix in patients with RV-PA conduit with
      potential implications for poor ventricular performance. We conclude that the
      current available evidence, although weak, does not show any adverse effects of
      ventriculotomy on ventricular performance in patients with Sano shunt in the
      short- and medium-term. However, all the existing studies are limited by small
      numbers, non-randomised design and retrospective nature with failure of
      correlation of echocardiographic indices to clinical outcomes. It is expected
      that the Pediatric Heart Network randomised controlled trial will address this
      important issue.

PMID- 20053700
TI  - Biatrial reduction plasty with reef imbricate technique as an adjunct to maze
      procedure for permanent atrial fibrillation associated with giant left atria.
AB  - Success of the modified maze procedure after valvular operation with giant atria
      and permanent atrial fibrillation (AF) remains suboptimal. We report an
      aggressive approach for these patients utilizing biatrial reduction plasty with a
      reef imbricate suture technique concomitantly with valvular and maze procedure
      for AF. From January 1999 to December 2006, 122 consecutive Chinese patients with
      permanent AF and biatrial enlargement who required mitral valve+/-tricuspid valve
      (TV) surgery underwent aggressive left atrial reduction combined with
      radiofrequency bipolar full maze procedure. Left atrial dimensions were measured
      by TTE or TEE. There were 71 women (58.1%) and 51 men (41.9%) and their mean age
      was 45+/-9.5 years. Mean duration of AF was 48.4+/-21.4 months. All patients
      underwent left atrial reduction plasty with reef imbricate suture technique and
      full maze procedure. Their preoperative left atria measured 64+/-12 mm in the
      enlarged left atria (ELA) group and 86+/-17 mm in the giant left atria (GLA).
      Mitral valve replacement (MVR) combined with TV repair was performed in 102
      patients (83%) while 21 patients underwent MVRs combined with aortic valve
      replacements (17%). Sixty-six (54%) patients required additional procedures and
      61 (50%) of the patients also underwent left atrial appendage clot evacuation.
      Postoperative left atrial size was reduced to 49+/-8 mm (ELA) and 51+/-11 mm
      (GLA), respectively (P<0.05). Ninety-three of 122 (76%) patients were restored in
      normal sinus rhythm after one year clinical follow-up. Aggressive biatrial
      reduction plasty combined with full maze procedure is an effective treatment for
      patients with permanent AF undergoing concomitant valvular surgery. Further
      studies utilizing the reef imbricate suture technique for atrial reduction need
      to subsequently be evaluated.

PMID- 20053701
TI  - A revised scheme for developmental pathways of hematopoietic cells: the myeloid
      based model.
AB  - Blood cells comprise very diverse cell types with a wide range of crucial
      functions; however, they share a common progenitor cell type-the hematopoietic
      stem cell (HSC). Clarifying how HSCs differentiate into these diverse cell types
      is important for understanding how they attain their various functions and offers
      the potential for therapeutic manipulation. Various theories exist about how HSCs
      diversify; in particular, one model (the 'classical' model) proposes that
      lymphocytes and myelo-erythroid lineages branch separately at an early stage of
      hematopoiesis, whereas another model (the 'myeloid-based' model) proposes that
      the myeloid potential is retained for much longer among cells that can become
      lymphocytes. This article describes and compares these models and outlines recent
      evidence supporting the myeloid-based model.

PMID- 20053702
TI  - Acute toxicity of a single dose DATR, recombinant soluble human TRAIL mutant, in
      rodents and crab-eating macaques.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported
      to possess activity of inducing apoptosis in variety of tumor cells in
      preclinical models. Several mutational versions of TRAIL have been studied as
      promising agents for cancer therapy and the recombinant soluble human TRAIL
      mutant (DATR) is one of them. The objective of the present study was to provide
      possible toxic target organs and proposal non-toxic dose level of DATR for
      clinical usage. Rodents and crab-eating macaques were used to estimate potential
      adverse effects of DATR following a single dose administration. The median lethal
      dose (LD(50)) of intravenous injection to rats and mice was determined as 262.0
      and 1018.0 mg/kg b.w., respectively. The LD(50) of intraperitoneal administration
      to mice was found to be 1432.1 mg/kg b.w. The main changes in macaques were found
      in the following aspects. Hematology analysis revealed an obvious decrease of red
      blood cell count (RBC), hemoglobin (HB) and hematocrit (HCT) after injection.
      Serum biochemical analysis showed an apparent increase of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL),
      blood urea nitrogen (BUN) and creatinine (Crea). Furthermore, inflammatory cell
      infiltrate in liver and kidney was found by microscope. All the disorders
      suggested that liver, renal and hematological systems might be the target
      effectors of toxic effect induced by DATR. Based on the results of this study,
      the no observed-adverse-effect level (NOAEL) and the lowest observed-adverse
      effect level of DATR in macaques are 90.0 and 135.0 mg/kg b.w., respectively.

PMID- 20053703
TI  - Vitamin C prevents DNA damage induced by renovascular hypertension in multiple
      organs of Wistar rats.
AB  - The aim of this study was to investigate, through the single-cell gel (comet)
      assay, whether vitamin C is able to protect against renovascular hypertension
      induced genotoxicity in multiple organs. A total of 32 male Wistar rats were
      divided into four groups: negative control (n = 6); animals treated with vitamin
      C (n = 6); hypertensive rats (n = 10) and hypertensive rats and treated with
      vitamin C (n = 10). Hypertension was induced as a result of partial obstruction
      of the left renal artery by means of a silver clip during 6 weeks. Vitamin C was
      administered at 150 mg/kg during 7 consecutive days before the end of the
      experimental period. The results showed that vitamin C was able to protect blood
      cells against hypertension-induced genotoxicity. Brain, liver and heart cells
      were also protected by vitamin C following hypertension-induced genotoxic damage.
      Regarding blood pressure, vitamin C reduced the hypertensive state. In
      conclusion, our results suggest that vitamin C can prevent hypertension-induced
      DNA damage in blood, liver, brain and heart cells as well as to normalize the
      blood pressure of rats.

PMID- 20053704
TI  - MG132 as a proteasome inhibitor induces cell growth inhibition and cell death in
      A549 lung cancer cells via influencing reactive oxygen species and GSH level.
AB  - Carbobenzoxy-Leu-Leu-leucinal (MG132) as a proteasome inhibitor has been shown to
      induce apoptotic cell death through formation of reactive oxygen species (ROS).
      In the present study, we evaluated the effects of MG132 on the growth of A549
      lung cancer cells in relation to cell growth, ROS and glutathione (GSH) levels.
      Treatment with MG132 inhibited the growth of A549 cells with an IC(50) of
      approximately 20 microM at 24 hours. DNA flow cytometric analysis indicated that
      0.5 approximately 30 microM MG132 induced a G1 phase arrest of the cell cycle in
      A549 cells. Treatment with 10 or 30 microM MG132 also induced apoptosis, as
      evidenced by sub-G1 cells and annexin V staining cells. This was accompanied by
      the loss of mitochondrial membrane potential (MMP; Delta psi m). The
      intracellular ROS levels including O(2) (*-) were strongly increased in 10 or 30
      microM MG132-treated A549 cells but were down-regulated in 0.1, 0.5 or 1 microM
      MG132-treated cells. Furthermore, 10 or 30 microM MG132 increased mitochondrial
      O(2) (*- ) level but 0.1, 0.5 or 1 microM MG132 decreased that. In addition, 10
      or 30 microM MG132 induced GSH depletion in A549 cells. In conclusion, MG132
      inhibited the growth of human A549 cells via inducing the cell cycle arrest as
      well as triggering apoptosis, which was in part correlated with the changes of
      ROS and GSH levels. Our present data provide important information on the anti
      growth mechanisms of MG132 in A549 lung cancer cells in relation to ROS and GSH.

PMID- 20053705
TI  - Antiserum against Raoultella terrigena ATCC 33257 identifies a large number of
      Raoultella and Klebsiella clinical isolates as serotype O12.
AB  - Raoultella terrigena ATCC 33257, recently reclassified from the genus Klebsiella,
      is a drinking water isolate and belongs to a large group of non-typeable
      Klebsiella and Raoultella strains. Using an O-antiserum against a capsule
      deficient mutant of this strain, we could show a high prevalence (10.5%) of the
      R. terrigena O-serotype among non-typeable, clinical Klebsiella and Raoultella
      isolates. We observed a strong serological cross-reaction with the K. pneumoniae
      O12 reference strain, indicating that a large percentage of these non-typeable
      strains may belong to the O12 serotype, although these are currently not
      detectable by the K. pneumoniae O12 reference antiserum in use. Therefore, we
      analyzed the O-polysaccharide (O-PS) structure and genetic organization of the wb
      gene cluster of R. terrigena ATCC 33257, and both confirmed a close relation of
      R. terrigena and K. pneumoniae O12. The two strains possess an identical O-PS,
      lipopolysaccharide core structure, and genetic organization of the wb gene
      cluster. Heterologous expression of the R. terrigena wb gene cluster in
      Escherichia coli K-12 resulted in the WecA-dependent synthesis of an O-PS
      reactive with the K. pneumoniae O12 antiserum. The serological data presented
      here suggest a higher prevalence of the O12-serotype among Klebsiella and
      Raoultella isolates than generally assumed.

PMID- 20053706
TI  - Images in vascular medicine. Isolated lower extremity vasculitis in a patient
      with polymyalgia rheumatica.

PMID- 20053707
TI  - Images in vascular medicine. Giant iliac artery aneurysms.

PMID- 20053708
TI  - Macrophages: do they impact AIDS progression more than CD4 T cells?
AB  - Destruction of CD4(+) T cells is considered to be the main cause of
      immunodeficiency manifested by opportunistic infections in HIV-1-infected humans,
      as well as in SIV-infected macaques. We propose that monocyte/macrophage lineage
      cells also play an important role in the pathogenesis of AIDS, based on our
      recent work with the SIV/rhesus macaque animal model. We propose that damage to
      CD4(+) T cells is important and readily apparent, but damage to
      monocyte/macrophage lineage cells, although less obvious, may provide the missing
      link to predict the onset of opportunistic infections and progression to AIDS.

PMID- 20053709
TI  - Channel-like characteristics of the low-affinity barley phosphate transporter
      PHT1;6 when expressed in Xenopus oocytes.
AB  - Remobilization of inorganic phosphate (P(i)) within a plant is critical for
      sustaining growth and seed production under external P(i) fluctuation. The barley
      (Hordeum vulgare) transporter HvPHT1;6 has been implicated in P(i)
      remobilization. In this report, we expressed HvPHT1;6 in Xenopus laevis oocytes,
      allowing detailed characterization of voltage-dependent fluxes and currents
      induced by HvPHT1;6. HvPHT1;6 increased efflux of P(i) near oocyte resting
      membrane potentials, dependent on external P(i) concentration. Time-dependent
      inward currents were observed when membrane potentials were more negative than 
      160 mV, which was consistent with nH(+):HPO(4)(2-) (n > 2) cotransport, based on
      simultaneous radiotracer and oocyte voltage clamping, dependent upon P(i)
      concentration gradient and pH. Time- and voltage-dependent inward currents
      through HvPHT1;6 were also observed for SO(4)(2-)and to a lesser degree for
      NO(3)(-)Cl(-)but not for malate. Inward and outward currents showed linear
      dependence on the concentration of external HPO(4)(2-)similar to low-affinity
      P(i) transport in plant studies. The electrophysiological properties of HvPHT1;6,
      which locates to the plasma membrane when expressed in onion (Allium cepa)
      epidermal cells, are consistent with its suggested role in the remobilization of
      P(i) in barley plants.

PMID- 20053710
TI  - Chloroplastic phosphoadenosine phosphosulfate metabolism regulates basal levels
      of the prohormone jasmonic acid in Arabidopsis leaves.
AB  - Levels of the enzymes that produce wound response mediators have to be controlled
      tightly in unwounded tissues. The Arabidopsis (Arabidopsis thaliana) fatty acid
      oxygenation up-regulated8 (fou8) mutant catalyzes high rates of alpha -linolenic
      acid oxygenation and has higher than wild-type levels of the alpha -linolenic
      acid-derived wound response mediator jasmonic acid (JA) in undamaged leaves. fou8
      produces a null allele in the gene SAL1 (also known as FIERY1 or FRY1).
      Overexpression of the wild-type gene product had the opposite effect of the null
      allele, suggesting a regulatory role of SAL1 acting in JA synthesis. The
      biochemical phenotypes in fou8 were complemented when the yeast (Saccharomyces
      cerevisiae) sulfur metabolism 3'(2'), 5'-bisphosphate nucleotidase MET22 was
      targeted to chloroplasts in fou8. The data are consistent with a role of SAL1 in
      the chloroplast-localized dephosphorylation of 3'-phospho-5'-adenosine
      phosphosulfate to 5'-adenosine phosphosulfate or in a closely related reaction
      (e.g. 3',5'-bisphosphate dephosphorylation). Furthermore, the fou8 phenotype was
      genetically suppressed in a triple mutant (fou8 apk1 apk2) affecting
      chloroplastic 3'-phospho-5'-adenosine phosphosulfate synthesis. These results
      show that a nucleotide component of the sulfur futile cycle regulates early steps
      of JA production and basal JA levels.

PMID- 20053711
TI  - Fluorescence resonance energy transfer-sensitized emission of yellow cameleon
      3.60 reveals root zone-specific calcium signatures in Arabidopsis in response to
      aluminum and other trivalent cations.
AB  - Fluorescence resonance energy transfer-sensitized emission of the yellow cameleon
      3.60 was used to study the dynamics of cytoplasmic calcium ([Ca(2+)](cyt)) in
      different zones of living Arabidopsis (Arabidopsis thaliana) roots. Transient
      elevations of [Ca(2+)](cyt) were observed in response to glutamic acid (Glu),
      ATP, and aluminum (Al(3+)). Each chemical induced a [Ca(2+)](cyt) signature that
      differed among the three treatments in regard to the onset, duration, and shape
      of the response. Glu and ATP triggered patterns of [Ca(2+)](cyt) increases that
      were similar among the different root zones, whereas Al(3+) evoked [Ca(2+)](cyt)
      transients that had monophasic and biphasic shapes, most notably in the root
      transition zone. The Al(3+)-induced [Ca(2+)](cyt) increases generally started in
      the maturation zone and propagated toward the cap, while the earliest
      [Ca(2+)](cyt) response after Glu or ATP treatment occurred in an area that
      encompassed the meristem and elongation zone. The biphasic [Ca(2+)](cyt)
      signature resulting from Al(3+) treatment originated mostly from cortical cells
      located at 300 to 500 mu m from the root tip, which could be triggered in part
      through ligand-gated Glu receptors. Lanthanum and gadolinium, cations commonly
      used as Ca(2+) channel blockers, elicited [Ca(2+)](cyt) responses similar to
      those induced by Al(3+). The trivalent ion-induced [Ca(2+)](cyt) signatures in
      roots of an Al(3+)-resistant and an Al(3+)-sensitive mutant were similar to those
      of wild-type plants, indicating that the early [Ca(2+)](cyt) changes we report
      here may not be tightly linked to Al(3+) toxicity but rather to a general
      response to trivalent cations.

PMID- 20053712
TI  - CORNET: a user-friendly tool for data mining and integration.
AB  - As an overwhelming amount of functional genomics data have been generated, the
      retrieval, integration, and interpretation of these data need to be facilitated
      to enable the advance of (systems) biological research. For example, gathering
      and processing microarray data that are related to a particular biological
      process is not straightforward, nor is the compilation of protein-protein
      interactions from numerous partially overlapping databases identified through
      diverse approaches. However, these tasks are inevitable to address the following
      questions. Does a group of differentially expressed genes show similar expression
      in diverse microarray experiments? Was an identified protein-protein interaction
      previously detected by other approaches? Are the interacting proteins encoded by
      genes with similar expression profiles and localization? We developed CORNET (for
      CORrelation NETworks) as an access point to transcriptome, protein interactome,
      and localization data and functional information on Arabidopsis (Arabidopsis
      thaliana). It consists of two flexible and versatile tools, namely the
      coexpression tool and the protein-protein interaction tool. The ability to browse
      and search microarray experiments using ontology terms and the incorporation of
      personal microarray data are distinctive features of the microarray repository.
      The coexpression tool enables either the alternate or simultaneous use of diverse
      expression compendia, whereas the protein-protein interaction tool searches
      experimentally and computationally identified protein-protein interactions.
      Different search options are implemented to enable the construction of
      coexpression and/or protein-protein interaction networks centered around multiple
      input genes or proteins. Moreover, networks and associated evidence are
      visualized in Cytoscape. Localization is visualized in pie charts, thereby
      allowing multiple localizations per protein. CORNET is available at
      http://bioinformatics.psb.ugent.be/cornet.

PMID- 20053713
TI  - Hypereosinophilic syndrome and clonal eosinophilia: point-of-care diagnostic
      algorithm and treatment update.
AB  - Acquired eosinophilia is operationally categorized into secondary, clonal, and
      idiopathic types. Causes of secondary eosinophilia include parasite infections,
      allergic or vasculitis conditions, drugs, and lymphoma. Clonal eosinophilia is
      distinguished from idiopathic eosinophilia by the presence of histologic,
      cytogenetic, or molecular evidence of an underlying myeloid malignancy. The World
      Health Organization classification system for hematologic malignancies recognizes
      2 distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia,
      not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and
      mutations involving platelet-derived growth factor receptor alpha/beta or
      fibroblast growth factor receptor 1. Clonal eosinophilia might also accompany
      other World Health Organization-defined myeloid malignancies, including chronic
      myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia,
      and systemic mastocytosis. Hypereosinophilic syndrome, a subcategory of
      idiopathic eosinophilia, is defined by the presence of a peripheral blood
      eosinophil count of 1.5 x 10(9)/L or greater for at least 6 months (a shorter
      duration is acceptable in the presence of symptoms that require eosinophil
      lowering therapy), exclusion of both secondary and clonal eosinophilia, evidence
      of organ involvement, and absence of phenotypically abnormal and/or clonal T
      lymphocytes. The presence of the latter defines lymphocytic variant hyper
      eosinophilia, which is best classified under secondary eosinophilia. In the
      current review, we provide a simplified algorithm for distinguishing the various
      causes of clonal and idiopathic eosinophilia and discuss current therapy,
      including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab).

PMID- 20053714
TI  - Proper layering is important for precisely timed activation of hippocampal mossy
      cells.
AB  - The mammalian cortex exhibits a laminated structure that may underlie optimal
      synaptic connectivity and support temporally precise activation of neurons. In
      'reeler' mice, the lack of the extracellular matrix protein Reelin leads to
      abnormal positioning of cortical neurons and disrupted layering. To address how
      these structural changes impact neuronal function, we combined
      electrophysiological and neuroanatomical techniques to investigate the synaptic
      activation of hippocampal mossy cells (MCs), the cell type that integrates the
      output of dentate gyrus granule cells (GCs). While somatodendritic domains of
      wild-type (WT) MCs were confined to the hilus, the somata and dendrites of reeler
      MCs were often found in the molecular layer, where the perforant path (PP)
      terminates. Most reeler MCs received aberrant monosynaptic excitatory input from
      the PP, whereas the disynaptic input to MCs via GCs was decreased and inhibition
      was increased. In contrast to the uniform disynaptic discharge of WT MCs, many
      reeler cells discharged with short, monosynaptic latencies, while others fired
      with long latencies over a broad temporal window in response to PP activation.
      Thus, disturbed lamination results in aberrant synaptic connectivity and altered
      timing of action potential generation. These results highlight the importance of
      a layered cortical structure for information processing.

PMID- 20053715
TI  - Cortical layer development and orientation is modulated by relative contributions
      of reelin-negative and -positive neurons in mouse chimeras.
AB  - Reelin is an important protein that is indispensable for cortical lamination. In
      the absence of Reelin, cortical layers fail to form due to inappropriate neuron
      migration and positioning. The inversion of cortical layers is attributed to
      failure of neurons to migrate past earlier-generated neurons although how Reelin
      insufficiency causes this is unclear. The issue is complicated by recent studies
      showing that very little Reelin is required for cortical layering. To test how
      variation in the number of Reelin-producing cells is linked to cortical
      lamination, we have employed Reelin(+/+) <--> Reelin(-/-) chimeras in which the
      number of Reelin-expressing neurons is adjusted. We found that the Reeler
      phenotype was rescued in chimeras with a large contribution of Reelin(+/+)
      neurons; conversely in chimeras with a weak contribution by Reelin(+/+) neurons,
      the mutant phenotype remained. However, increasing the number of Reelin(+/+)
      neurons beyond an unknown threshold resulted in partial rescue, with the
      formation of a correctly layered secondary cortex lying on top of an inverted
      mutant cortex. Therefore, the development of cortical layers in the correct order
      requires a minimal level of Reelin protein to be present although paradoxically,
      this is insufficient to prevent the simultaneous formation of inverted cortical
      layers in the same hemisphere.

PMID- 20053717
TI  - Post-treatment evaluation of a magnetic activator device in Class II high-angle
      malocclusions.
AB  - SUMMARY: The purpose of this study was to evaluate changes in dentofacial growth
      before, during, and after use of a magnetic activator device (MAD) II in high
      angle Class II division 1 patients. Lateral cephalometric and hand-wrist
      radiographs of 10 patients (six girls and four boys) with an average
      chronological age of 10 years 5 months were obtained at the beginning of the
      observation period (T1, 9.5 months), beginning of MAD II application (T2), at the
      end of the treatment (T3), and approximately 4 years after the end of treatment
      (T4). Thirteen linear, 1 ratio, and 10 angular measurements were evaluated.
      Paired t-tests were used for statistical evaluation of differences that occurred
      between the time points. The increase in gonial angle, GnGoAr angle, S-N, Co-Gn,
      Go-Ar, ANS-Me, S-Go, and N-Me distances and the decrease of overjet, U1-NA
      distance, and ANB angle were statistically significant during the treatment. At
      T4, there was a decrease in gonial angle and U1-NA distance, which was
      significant. The changes as a result of treatment were stable at T4.

PMID- 20053716
TI  - The estrogen receptor-alpha in osteoclasts mediates the protective effects of
      estrogens on cancellous but not cortical bone.
AB  - Estrogens attenuate osteoclastogenesis and stimulate osteoclast apoptosis, but
      the molecular mechanism and contribution of these effects to the overall
      antiosteoporotic efficacy of estrogens remain controversial. We selectively
      deleted the estrogen receptor (ER)alpha from the monocyte/macrophage cell lineage
      in mice (ERalpha(LysM)(-/-)) and found a 2-fold increase in osteoclast
      progenitors in the marrow and the number of osteoclasts in cancellous bone, along
      with a decrease in cancellous bone mass. After loss of estrogens these mice
      failed to exhibit the expected increase in osteoclast progenitors, the number of
      osteoclasts in bone, and further loss of cancellous bone. However, they lost
      cortical bone indistinguishably from their littermate controls. Mature
      osteoclasts from ERalpha(LysM)(-/-) were resistant to the proapoptotic effect of
      17beta-estradiol. Nonetheless, the effects of estrogens on osteoclasts were
      unhindered in mice bearing an ERalpha knock-in mutation that prevented binding to
      DNA. Moreover, a polymeric form of estrogen that is not capable of stimulating
      the nuclear-initiated actions of ERalpha was as effective as 17beta-estradiol in
      inducing osteoclast apoptosis in cells with the wild-type ERalpha. We conclude
      that estrogens attenuate osteoclast generation and life span via cell autonomous
      effects mediated by DNA-binding-independent actions of ERalpha. Elimination of
      these effects is sufficient for loss of bone in the cancellous compartment in
      which complete perforation of trabeculae by osteoclastic resorption precludes
      subsequent refilling of the cavities by the bone-forming osteoblasts. However,
      additional effects of estrogens on osteoblasts, osteocytes, and perhaps other
      cell types are required for their protective effects on the cortical compartment,
      which constitutes 80% of the skeleton.

PMID- 20053718
TI  - Continuous forces are more effective than intermittent forces in expanding
      sutures.
AB  - SUMMARY: While both intermittent and continuous forces are commonly used to
      expand sutures, it remains unclear which force is most effective. Using nickel
      titanium (NiTi) open coil springs (50 g) and 3 mm long miniscrew implants (MSIs)
      for skeletal anchorage, intermittent and continuous forces were used to expand
      the midsagittal sutures in 18 New Zealand white juvenile male rabbits, 11 weeks
      of age, for 29 days. In the intermittent group, expansion forces of 50 g were
      delivered for 5 days (on) and paused for 1 day (off); the on/off cycles were
      repeated five times. Expansion forces of 50 g were delivered for 29 consecutive
      days in the continuous group. Longitudinal biometric and histomorphometric
      analyses were performed to evaluate sutural separation and bone formation using
      implanted tantalum bone markers and fluorescent bone labelling, respectively.
      Multilevel modelling procedures were undertaken to compare the groups and time
      intervals. Continuous forces produced significantly greater overall sutural
      separation (1.3 mm) than intermittent forces (0.8 mm). Although they were
      delivered over a period of time 86 per cent as long, intermittent forces produced
      only 61 per cent of the sutural separation of continuous forces. Between days 7
      and 17, continuous forces resulted in significantly greater mineral apposition
      and bone formation rates than intermittent forces. Intermittent forces produced
      approximately 59 per cent as much mineral apposition and 61 per cent as much bone
      formation as continuous forces. Due to greater sutural separation and bone
      formation, continuous forces provide a more effective approach for separating
      sutures than intermittent forces.

PMID- 20053719
TI  - Soft tissue profile changes following maxillary protraction in Class III
      subjects.
AB  - SUMMARY: The dentoskeletal effects of maxillary protraction (MP) therapy have
      been extensively investigated, while those relating to soft tissue profile
      changes are limited. Thus, the aim of this study was to determine the degree of
      soft tissue profile changes following MP therapy. The material consisted of the
      cephalometric films of 24 female subjects (12.69 +/- 1.08 years) with a Class III
      malocclusion who underwent MP therapy; these were compared with a control group
      of 15 females (12.13 +/- 0.63 years) with a Class I occlusion and matched for
      chronological age and observation period. Cephalometric films were available for
      all subjects before (T1) and after (T2) treatment/observation. The initial
      measurements and treatment/control changes were compared between the groups by
      means of a Student's t-test. The subjects in the MP group had a concave facial
      profile when compared with the controls. Comparison of the changes induced by MP
      therapy showed that the maxilla and surrounding soft tissues showed significant
      anterior movement (P < 0.001), whereas the mandible and surrounding soft tissues
      showed a backward and downward rotation. The improvement in facial profile
      predominantly resulted from maxillary soft tissue changes and mandibular hard
      tissue changes. The concave soft tissue profiles of the Class III subjects were
      corrected by anterior movement of the maxilla and a concomitant increase in the
      fullness of the upper lip. The concave skeletal profiles were, however, corrected
      mainly by backward and downward rotation of the mandible.

PMID- 20053720
TI  - Spinal manipulation compared with back school and with individually delivered
      physiotherapy for the treatment of chronic low back pain: a randomized trial with
      one-year follow-up.
AB  - OBJECTIVE: To compare spinal manipulation, back school and individual
      physiotherapy in the treatment of chronic low back pain. DESIGN: Randomized
      trial, 12-month follow-up. SETTING: Outpatient rehabilitation department.
      PARTICIPANTS: 210 patients with chronic, non-specific low back pain, 140/210
      women, age 59 +/- 14 years. INTERVENTIONS: Back school and individual
      physiotherapy scheduled 15 1-hour-sessions for 3 weeks. Back school included:
      group exercise, education/ ergonomics; individual physiotherapy: exercise,
      passive mobilization and soft-tissue treatment. Spinal manipulation, given
      according to Manual Medicine, scheduled 4 to 6 20'-sessions once-a-week. OUTCOME:
      Roland Morris Disability Questionnaire (scoring 0-24) and Pain Rating Scale
      (scoring 0-6) were assessed at baseline, discharge 3, 6, and 12 months. RESULTS:
      205 patients completed the study. At discharge, disability score decreased by 3.7
      +/- 4.1 for back school, 4.4 +/- 3.7 for individual physiotherapy, 6.7 +/- 3.9
      for manipulation; pain score reduction was 0.9 +/- 1.1, 1.1 +/- 1.0, 1.0 +/- 1.1,
      respectively. At 12 months, disability score reduction was 4.2 +/- 4.8 for back
      school, 4.0 +/- 5.1 for individual physiotherapy, 5.9 +/- 4.6 for manipulation;
      pain score reduction was 0.7 +/- 1.2, 0.4 +/- 1.3, and 1.5 +/- 1.1, respectively.
      Spinal manipulation was associated with higher functional improvement and long
      term pain relief than back school or individual physiotherapy, but received more
      further treatment at follow-ups (P < 0.001); pain recurrences and drug intake
      were also reduced compared to back school (P < 0.05) or individual physiotherapy
      (P < 0.001). CONCLUSIONS: Spinal manipulation provided better short and long-term
      functional improvement, and more pain relief in the follow-up than either back
      school or individual physiotherapy.

PMID- 20053721
TI  - An original field evaluation test for chronic obstructive pulmonary disease
      population: the six-minute stepper test.
AB  - PURPOSE: The aim of this study was to evaluate a new field test, the six-minute
      stepper test (6-MST), by studying its reproducibility, sensitivity and validity.
      METHODS: After a familiarization test, 16 patients with chronic obstructive
      pulmonary disease (COPD) and 15 healthy subjects performed two six-minute stepper
      tests per day over three evaluation days. Ten of the 16 patients with COPD also
      performed a six-minute walking test (6-MWT) with an analysis of gas exchange to
      compare the metabolic requirements of the two tests. Dyspnoea Borg values were
      evaluated with Borg's CR-10 scale. RESULTS: The mean (SD) scores for the COPD
      group for the first and second six-minute stepper tests were 382.49 (106.01) and
      412.45 (118.39) strokes/6 minutes, respectively. Crossed comparison between the
      first or the second six-minute stepper tests of each evaluation day revealed no
      significant difference, indicating the reproducibility of the test. The
      sensitivity was demonstrated by a significantly higher performance in the healthy
      group (P < 0.001), demonstrating the ability of the test to detect two groups
      with different fitness levels. Finally, mean dyspnoea Borg values (SD) were
      significantly lower (P < 0.05) during the six-minute stepper test than during 6
      MWT (2.5 (1.5) versus 3.1 (1.2)). CONCLUSIONS: This study demonstrated that the
      six-minute stepper test is a reproducible, sensitive, secure, well-tolerated and
      feasible test for patients with COPD. The reproducibility and sensitivity of the
      six-minute stepper test suggests that this test could be used in the evaluation
      of exercise tolerance in patients with COPD.

PMID- 20053723
TI  - Mental health service users' perceptions and experiences of sedation, seclusion
      and restraint.
AB  - BACKGROUND: Sedation, seclusion or restraint are recognized methods of containing
      a person experiencing an acute psychotic episode with behavioural disturbance
      which has not responded to verbal or non-sedating pharmacological interventions.
      These interventions pose significant ethical and practical challenges to service
      providers who are responsible for safeguarding the human rights of mental health
      service users. AIMS: In a collaborative two-phase study between mental health
      care providers and mental health service users, the perceptions and experiences
      of a group of service users who have been exposed to sedation, seclusion and
      restraint were explored. METHOD: A focus group was conducted with eight service
      users. The content of the focus group was transcribed and themes were identified
      using thematic analysis. These were presented to a second focus group consisting
      of eight other service users for validation and comment. Based on the results of
      the focus groups, a questionnaire was developed and administered to a convenience
      sample of 43 service users in three localities. RESULTS: Service users reported
      inadequate communication between them and service providers and perceived that
      their human rights had been infringed during acute episodes of illness. METHODS:
      of containment were often seen as punitive rather than therapeutic. Sedation was
      most frequently used and was considered to be least distressing. Observing
      methods of forced/involuntary containment caused further distress. CONCLUSIONS:
      There is a need to humanize service users' experiences during episodes of acute
      illness. Measures should include prevention of human rights abuses; minimization
      of isolation and distress; improvement of communication between service providers
      and service users; and promotion of attitudinal changes which reflect respect for
      other people's dignity.

PMID- 20053725
TI  - A conserved lysine in the thyroid hormone receptor-alpha1 DNA-binding domain,
      mutated in hepatocellular carcinoma, serves as a sensor for transcriptional
      regulation.
AB  - Nuclear receptors are hormone-regulated transcription factors that play key roles
      in normal physiology and development; conversely, mutant nuclear receptors are
      associated with a wide variety of neoplastic and endocrine disorders. Typically,
      these receptor mutants function as dominant negatives and can interfere with wild
      type receptor activity. Dominant-negative thyroid hormone receptor (TR) mutations
      have been identified in over 60% of the human hepatocellular carcinomas analyzed.
      Most of these mutant TRs are defective for corepressor release or coactivator
      binding in vitro, accounting for their transcriptional defects in vivo. However,
      two HCC-TR mutants that function as dominant-negative receptors in cells display
      near-normal properties in vitro, raising questions about the molecular basis
      behind their transcriptional defects. We report here that a single amino acid
      substitution, located at the same position in the DNA-binding domain of both
      mutants, is responsible for their impaired transcriptional activation and
      dominant-negative properties. Significantly, this amino acid, K74 in TRalpha, is
      highly conserved in all known nuclear receptors and seems to function as an
      allosteric sensor that regulates the transcriptional activity of these receptors
      in response to binding to their DNA recognition sequences. We provide evidence
      that these two human hepatocellular carcinoma mutants have acquired dominant
      negative function as a result of disruption of this allosteric sensing. Our
      results suggest a novel mechanism by which nuclear receptors can acquire
      transcriptional defects and contribute to neoplastic disease.

PMID- 20053726
TI  - Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by
      inhibiting STAT3 and AKT signaling pathways.
AB  - Medulloblastomas are the most frequent malignant brain tumors in children.
      Sunitinib is an oral multitargeted tyrosine kinase inhibitor used in clinical
      trials as an antiangiogenic agent for cancer therapy. In this report, we show
      that sunitinib induced apoptosis and inhibited cell proliferation of both a short
      term primary culture (VC312) and an established cell line (Daoy) of human
      medulloblastomas. Sunitinib treatment resulted in the activation of caspase-3 and
      cleavage of poly(ADP-ribose) polymerase and upregulation of proapoptotic genes,
      Bak and Bim, and inhibited the expression of survivin, an antiapoptotic protein.
      Sunitinib treatment also downregulated cyclin E, cyclin D2, and cyclin D3 and
      upregulated p21Cip1, all of which are involved in regulating cell cycle. In
      addition, it inhibited phosphorylation of signal transducer and activator of
      transcription 3 (STAT3) and AKT (protein kinase B) in the tumor cells.
      Dephosphorylation of STAT3 (Tyr(705)) induced by sunitinib was helped by a
      reduction in activities of Janus-activated kinase 2 and Src. Additionally, sodium
      vanadate, an inhibitor of protein tyrosine phosphatases, partially blocked the
      inhibition of phosphorylated STAT3 by sunitinib. Loss of phosphorylated AKT after
      sunitinib treatment was accompanied by decreased phosphorylation of downstream
      proteins glycogen synthase kinase-3beta and mammalian target of rapamycin.
      Expression of a constitutively activated STAT3 mutant or myristoylated AKT
      partially blocked the effects of sunitinib in these tumor cells. Sunitinib also
      inhibited the migration of medulloblastoma tumor cells in vitro. These findings
      suggest the potential use of sunitinib for the treatment of pediatric
      medulloblastomas.

PMID- 20053727
TI  - DOC45, a novel DNA damage-regulated nucleocytoplasmic ATPase that is
      overexpressed in multiple human malignancies.
AB  - In this article, we report the characterization of a novel DNA damage-regulated
      gene, named DNA damage-regulated overexpressed in cancer 45 (DOC45). Our results
      indicate that DNA damage-inducing agents, including doxorubicin (adriamycin),
      etoposide, and ionizing and UV radiation, strongly downregulate DOC45 expression,
      whereas endoplasmic reticulum stress-inducing agents do not. Our results also
      indicate that DOC45 is overexpressed in several human malignancies, including
      cancers of the colon, rectum, ovary, lung, stomach, and uterus. DOC45 harbors
      conserved nucleotide triphosphate-binding motifs and is capable of ATP
      hydrolysis, findings that highlight its function as a novel ATPase. Although
      predominantly cytoplasmic, DOC45 exhibits a characteristic nucleocytoplasmic
      distribution and, on inhibition of nuclear export, predominantly accumulates in
      the nucleoli. These results suggest that DOC45 may shuttle between nucleus and
      cytoplasm to carry out its function. Our results also indicate that DOC45
      expression is enhanced during oncogenic Ras-mediated transformation and that its
      expression is linked to phosphoinositide 3-kinase signaling pathway. Furthermore,
      short hairpin RNA-mediated knockdown of DOC45 in human colon cancer cells
      inhibits their proliferation and enhances cellular sensitivity to doxorubicin
      induced cell death, suggesting that DOC45 plays an important role in cell
      proliferation and survival. Collectively, our results indicate that DOC45 is a
      novel ATPase that is linked to cellular stress response and tumorigenesis, and
      may also serve as a valuable tumor marker.

PMID- 20053728
TI  - Yeast arginine methyltransferase Hmt1p regulates transcription elongation and
      termination by methylating Npl3p.
AB  - The heterogeneous nuclear ribonucleoprotein Npl3p of budding yeast is a substrate
      of arginine methyltransferase Hmt1p, but the role of Hmt1p in regulating Npl3p's
      functions in transcription antitermination and elongation were unknown. We found
      that mutants lacking Hmt1p methyltransferase activity exhibit reduced recruitment
      of Npl3p, but elevated recruitment of a component of mRNA cleavage/termination
      factor CFI, to the activated GAL10-GAL7 locus. Consistent with this, hmt1 mutants
      displayed increased termination at the defective gal10-Delta56 terminator.
      Remarkably, hmt1Delta cells also exhibit diminished recruitment of elongation
      factor Tho2p and a reduced rate of transcription elongation in vivo. Importantly,
      the defects in Npl3p and Tho2p recruitment, antitermination and elongation in
      hmt1Delta cells all were mitigated by substitutions in Npl3p RGG repeats that
      functionally mimic arginine methylation by Hmt1p. Thus, Hmt1p promotes elongation
      and suppresses termination at cryptic terminators by methylating RGG repeats in
      Npl3p. As Hmt1p stimulates dissociation of Tho2p from an Npl3p-mRNP complex, it
      could act to recycle these elongation and antitermination factors back to sites
      of ongoing transcription.

PMID- 20053729
TI  - Custom human endogenous retroviruses dedicated microarray identifies self-induced
      HERV-W family elements reactivated in testicular cancer upon methylation control.
AB  - Endogenous retroviruses (ERVs) are an inherited part of the eukaryotic genomes,
      and represent approximately 400,000 loci in the human genome. Human endogenous
      retroviruses (HERVs) can be divided into distinct families, composed of
      phylogenetically related but structurally heterogeneous elements. The majority of
      HERVs are silent in most physiological contexts, whereas a significant expression
      is observed in pathological contexts, such as cancers. Owing to their repetitive
      nature, few of the active HERV elements have been accurately identified. In
      addition, there are no criteria defining the active promoters among HERV long
      terminal repeats (LTRs). Hence, it is difficult to understand the HERV
      (de)regulation mechanisms and their implication on the physiopathology of the
      host. We developed a microarray to specifically detect the LTR-containing
      transcripts from the HERV-H, HERV-E, HERV-W and HERV-K(HML-2) families. HERV
      transcriptome was analyzed in the placenta and seven normal/tumoral match-pair
      samples. We identified six HERV-W loci overexpressed in testicular cancer,
      including a usually placenta-restricted transcript of ERVWE1. For each locus,
      specific overexpression was confirmed by quantitative RT-PCR, and comparison of
      the activity of U3 versus U5 regions suggested a U3-promoted transcription
      coupled with 5'R initiation. The analysis of DNA from tumoral versus normal
      tissue revealed that hypomethylation of U3 promoters in tumors is a prerequisite
      for their activation.

PMID- 20053730
TI  - Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD
      dependent gene expression.
AB  - Gene promoters are enriched in guanine clusters that potentially fold into
      quadruplex structures. Such quadruplexes were implicated in the regulation of
      gene expression, plausibly by interacting with transcription factors. We showed
      previously that homodimers of the myogenic transcription factor MyoD bound in
      vitro most tightly bimolecular quadruplexes of promoter sequences of muscle
      specific genes. By contrast, MyoD-E47 heterodimers formed tighter complexes with
      d(CANNTG) E-box motifs that govern muscle gene expression. Here, we show that DNA
      quadruplexes enhance in vivo MyoD and E-box-driven expression of a firefly
      luciferase (FL) reporter gene. HEK293 cells were transfected with FL expressing
      p4RTK-FL vector alone or together with MyoD expressing pEMSV-MyoD plasmid, with
      quadruplexes of alpha7 integrin or sarcomeric mitochondrial creatine kinase
      (sMtCK) muscle gene promoters or with a combination thereof. Whereas MyoD
      elevated by approximately 10-fold the levels of FL mRNA and protein, the DNA
      quadruplexes by themselves did not affect FL expression. However, together with
      MyoD, quadruplex DNA increased by approximately 35-fold the amounts of FL mRNA
      and protein. Without affecting its expression, DNA quadruplexes bound MyoD in the
      cells. Based on these results, we propose models for the regulation of muscle
      gene transcription by direct interaction of MyoD with promoter quadruplex
      structures.

PMID- 20053732
TI  - Real-time classification of datasets with hardware embedded neuromorphic neural
      networks.
AB  - Neuromorphic artificial neural networks attempt to understand the essential
      computations that take place in the dense networks of interconnected neurons
      making up the central nervous systems in living creatures. This article
      demonstrates that artificial spiking neural networks--built to resemble the
      biological model--encoding information in the timing of single spikes, are
      capable of computing and learning clusters from realistic data. It shows how a
      spiking neural network based on spike-time coding can successfully perform
      unsupervised and supervised clustering on real-world data. A temporal encoding
      procedure of continuously valued data is developed, together with a hardware
      implementation oriented new learning rule set. Solutions that make use of
      embedded soft-core microcontrollers are investigated, to implement some of the
      most resource-consuming components of the artificial neural network. Details of
      the implementations are given, with benchmark application evaluation and test
      bench description. Measurement results are presented, showing real-time and
      adaptive data processing capabilities, comparing these to related findings in the
      specific literature.

PMID- 20053731
TI  - Commandeering a biological pathway using aptamer-derived molecular adaptors.
AB  - Induction of molecular proximity can mediate a discrete functional response in
      biological systems. Therefore, creating new and specific connectivity between non
      interacting proteins is a means of imposing rational control over biological
      processes. According to this principle, here we use composite RNA aptamers to
      generate molecular adaptors that link various 'target' molecules to a common
      'utility' molecule, with the utility molecule being an entry point to a pathway
      conscripted to process the target molecule. In particular, we created a bi
      functional aptamer that simultaneously binds to the green fluorescent protein
      (serving as a surrogate extracellular target) and the opsonin C3b/iC3b (serving
      as the utility molecule). This bi-functional aptamer enabled us to commandeer the
      C3-based opsonization-phagocytosis pathway to selectively transport an
      extracellular target into the lysosome for degradation. This novel strategy has
      the potential for powerful therapeutic applications with extracellular proteins
      involved in tumor development or surface markers on cancer cells as the target
      molecules.

PMID- 20053733
TI  - Genome variation discovery with high-throughput sequencing data.
AB  - The advent of high-throughput sequencing (HTS) technologies is enabling
      sequencing of human genomes at a significantly lower cost. The availability of
      these genomes is hoped to enable novel medical diagnostics and treatment,
      specific to the individual, thus launching the era of personalized medicine. The
      data currently generated by HTS machines require extensive computational analysis
      in order to identify genomic variants present in the sequenced individual. In
      this paper, we overview HTS technologies and discuss several of the plethora of
      algorithms and tools designed to analyze HTS data, including algorithms for read
      mapping, as well as methods for identification of single-nucleotide
      polymorphisms, insertions/deletions and large-scale structural variants and copy
      number variants from these mappings.

PMID- 20053734
TI  - Commentary: Managing scaling up: what are the key issues?

PMID- 20053735
TI  - Cardiovascular magnetic resonance prior to surgical treatment of chronic thrombo
      embolic pulmonary hypertension.

PMID- 20053736
TI  - The p38 signaling pathway upregulates expression of the Epstein-Barr virus LMP1
      oncogene.
AB  - The Epstein-Barr virus (EBV)-encoded LMP1 oncogene has a role in transformation,
      proliferation, and metastasis of several EBV-associated tumors. Furthermore, LMP1
      is critically involved in transformation and growth of EBV-immortalized B cells
      in vitro. The oncogenic properties of LMP1 are attributed to its ability to
      upregulate anti-apoptotic proteins and growth signals. The transcriptional
      regulation of LMP1 is dependent on the context of cellular and viral proteins
      present in the cell. Here, we investigated the effect of several signaling
      pathways on the regulation of LMP1 expression. Inhibition of p38 signaling, using
      p38-specific inhibitors SB203580 and SB202190, downregulated LMP1 in estrogen
      induced EREB2.5 cells. Similarly, p38 inhibition decreased trichostatin A-induced
      LMP1 expression in P3HR1 cells. Exogenous expression of p38 in lymphoblastoid
      cell lines (LCLs) led to an increase in LMP1 promoter activity in reporter
      assays, and this activation was mediated by the previously identified CRE site in
      the promoter. Inhibition of p38 by SB203580 and p38-specific small interfering
      RNA (siRNA) also led to a modest decrease in endogenous LMP1 expression in LCLs.
      Chromatin immunoprecipitation indicated decreased binding of CREB-ATF1 to the CRE
      site in the LMP1 promoter after inhibition of the p38 pathway in EREB2.5 cells.
      Taken together, our results suggest that an increase in p38 activation
      upregulates LMP1 expression. Since p38 is activated in response to stimuli such
      as stress or possibly primary infection, a transient upregulation of LMP1 in
      response to p38 may allow the cells to escape apoptosis. Since the p38 pathway
      itself is activated by LMP1, our results also suggest the presence of an
      autoregulatory loop in LMP1 upregulation.

PMID- 20053737
TI  - A single amino acid substitution in the capsid of foot-and-mouth disease virus
      can increase acid lability and confer resistance to acid-dependent uncoating
      inhibition.
AB  - The acid-dependent disassembly of foot-and-mouth disease virus (FMDV) is required
      for viral RNA release from endosomes to initiate replication. Although the FMDV
      capsid disassembles at acid pH, mutants escaping inhibition by NH(4)Cl of
      endosomal acidification were found to constitute about 10% of the viruses
      recovered from BHK-21 cells infected with FMDV C-S8c1. For three of these
      mutants, the degree of NH(4)Cl resistance correlated with the sensitivity of the
      virion to acid-induced inactivation of its infectivity. Capsid sequencing
      revealed the presence in each of these mutants of a different amino acid
      substitution (VP3 A123T, VP3 A118V, and VP2 D106G) that affected a highly
      conserved residue among FMDVs located close to the capsid interpentameric
      interfaces. These residues may be involved in the modulation of the acid-induced
      dissociation of the FMDV capsid. The substitution VP3 A118V present in mutant c2
      was sufficient to confer full resistance to NH(4)Cl and concanamycin A (a V
      ATPase inhibitor that blocks endosomal acidification) as well as to increase the
      acid sensitivity of the virion to an extent similar to that exhibited by mutant
      c2 relative to the sensitivity of the parental virus C-S8c1. In addition, the
      increased propensity to dissociation into pentameric subunits of virions bearing
      substitution VP3 A118V indicates that this replacement also facilitates the
      dissociation of the FMDV capsid.

PMID- 20053738
TI  - Involvement of ceramide in the propagation of Japanese encephalitis virus.
AB  - Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus and one of the
      most important flaviviruses in the medical and veterinary fields. Although
      cholesterol has been shown to participate in both the entry and replication steps
      of JEV, the mechanisms of infection, including the cellular receptors of JEV,
      remain largely unknown. To clarify the infection mechanisms of JEV, we generated
      pseudotype (JEVpv) and recombinant (JEVrv) vesicular stomatitis viruses bearing
      the JEV envelope protein. Both JEVpv and JEVrv exhibited high infectivity for the
      target cells, and JEVrv was able to propagate and form foci as did authentic JEV.
      Anti-JEV envelope antibodies neutralized infection of the viruses. Treatment of
      cells with inhibitors for vacuolar ATPase and clathrin-mediated endocytosis
      reduced the infectivity of JEVpv, suggesting that JEVpv enters cells via pH- and
      clathrin-dependent endocytic pathways. Although treatment of the particles of
      JEVpv, JEVrv, and JEV with cholesterol drastically reduced the infectivity as
      previously reported, depletion of cholesterol from the particles by treatment
      with methyl beta-cyclodextrin enhanced infectivity. Furthermore, treatment of
      cells with sphingomyelinase (SMase), which hydrolyzes membrane-bound
      sphingomyelin to ceramide, drastically enhanced infection with JEVpv and
      propagation of JEVrv, and these enhancements were inhibited by treatment with an
      SMase inhibitor or C(6)-ceramide. These results suggest that ceramide plays
      crucial roles in not only entry but also egress processes of JEV, and they should
      assist in the clarification of JEV propagation and the development of novel
      therapeutics against diseases caused by infection with flaviviruses.

PMID- 20053739
TI  - Biochemical and structural characterization of cathepsin L-processed Ebola virus
      glycoprotein: implications for viral entry and immunogenicity.
AB  - Ebola virus (EBOV) cellular attachment and entry is initiated by the envelope
      glycoprotein (GP) on the virion surface. Entry of this virus is pH dependent and
      associated with the cleavage of GP by proteases, including cathepsin L (CatL)
      and/or CatB, in the endosome or cell membrane. Here, we characterize the product
      of CatL cleavage of Zaire EBOV GP (ZEBOV-GP) and evaluate its relevance to entry.
      A stabilized recombinant form of the EBOV GP trimer was generated using a
      trimerization domain linked to a cleavable histidine tag. This trimer was
      purified to homogeneity and cleaved with CatL. Characterization of the trimeric
      product by N-terminal sequencing and mass spectrometry revealed three cleavage
      fragments, with masses of 23, 19, and 4 kDa. Structure-assisted modeling of the
      cathepsin L-cleaved ZEBOV-GP revealed that cleavage removes a glycosylated glycan
      cap and mucin-like domain (MUC domain) and exposes the conserved core residues
      implicated in receptor binding. The CatL-cleaved ZEBOV-GP intermediate bound with
      high affinity to a neutralizing antibody, KZ52, and also elicited neutralizing
      antibodies, supporting the notion that the processed intermediate is required for
      viral entry. Together, these data suggest that CatL cleavage of EBOV GP exposes
      its receptor-binding domain, thereby facilitating access to a putative cellular
      receptor in steps that lead to membrane fusion.

PMID- 20053740
TI  - Two kinetic patterns of epitope-specific CD8 T-cell responses following murine
      gammaherpesvirus 68 infection.
AB  - Murine gammaherpesvirus 68 (gammaHV68) provides an important experimental model
      for understanding mechanisms of immune control of the latent human
      gammaherpesviruses. Antiviral CD8 T cells play a key role throughout three
      separate phases of the infection: clearance of lytic virus, control of the
      latency amplification stage, and prevention of reactivation of latently infected
      cells. Previous analyses have shown that T-cell responses to two well
      characterized epitopes derived from ORF6 and ORF61 progress with distinct
      kinetics. ORF6(487)-specific cells predominate early in infection and then
      decline rapidly, whereas ORF61(524)-specific cells continue to expand through
      early latency, due to sustained epitope expression. However, the paucity of
      identified epitopes to this virus has limited our understanding of the overall
      complexities of CD8 T-cell immune control throughout infection. Here we screened
      1,383 predicted H-2(b)-restricted peptides and identified 33 responses, of which
      21 have not previously been reported. Kinetic analysis revealed a spectrum of T
      cell responses based on the rapidity of their decline after the peak acute
      response that generally corresponded to the expression patterns of the two
      previously characterized epitopes. The slowly declining responses that were
      maintained during latency amplification proliferated more rapidly and underwent
      maturation of functional avidity over time. Furthermore, the kinetics of decline
      was accelerated following infection with a latency-null mutant virus. Overall,
      the data show that gammaHV68 infection elicits a highly heterogeneous CD8 T-cell
      response that segregates into two distinctive kinetic patterns controlled by
      differential epitope expression during the lytic and latency amplification stages
      of infection.

PMID- 20053741
TI  - Highly pathogenic H5N1 avian influenza virus induces extracellular Ca2+ influx,
      leading to apoptosis in avian cells.
AB  - In this study, we show that the highly pathogenic H5N1 avian influenza virus
      (AIV) (A/crow/Kyoto/53/04 and A/chicken/Egypt/CL6/07) induced apoptosis in duck
      embryonic fibroblasts (DEF). In contrast, apoptosis was reduced among cells
      infected with low-pathogenic AIVs (A/duck/HK/342/78 [H5N2], A/duck/HK/820/80
      [H5N3], A/wigeon/Osaka/1/01 [H7N7], and A/turkey/Wisconsin/1/66 [H9N2]). Thus, we
      investigated the molecular mechanisms of apoptosis induced by H5N1-AIV infection.
      Caspase-dependent and -independent pathways contributed to the cytopathic
      effects. We further showed that, in the induction of apoptosis, the hemagglutinin
      of H5N1-AIV played a major role and its cleavage sequence was not critical. We
      also observed outer membrane permeabilization and loss of the transmembrane
      potential of the mitochondria of infected DEF, indicating that mitochondrial
      dysfunction was caused by the H5N1-AIV infection. We then analyzed Ca(2+)
      dynamics in the infected cells and demonstrated an increase in the concentration
      of Ca(2+) in the cytosol ([Ca(2+)](i)) and mitochondria ([Ca(2+)](m)) after H5N1
      AIV infection. Regardless, gene expression important for regulating Ca(2+) efflux
      from the endoplasmic reticulum did not significantly change after H5N1-AIV
      infection. These results suggest that extracellular Ca(2+) may enter H5N1-AIV
      infected cells. Indeed, EGTA, which chelates extracellular free Ca(2+),
      significantly reduced the [Ca(2+)](i), [Ca(2+)](m), and apoptosis induced by H5N1
      AIV infection. In conclusion, we identified a novel mechanism for influenza A
      virus-mediated cell death, which involved the acceleration of extracellular
      Ca(2+) influx, leading to mitochondrial dysfunction and apoptosis. These findings
      may be useful for understanding the pathogenesis of H5N1-AIV in avian species as
      well as the impact of Ca(2+) homeostasis on influenza A virus infection.

PMID- 20053742
TI  - The DR1 and DR6 first exons of human herpesvirus 6A are not required for virus
      replication in culture and are deleted in virus stocks that replicate well in T
      cell lines.
AB  - Human herpesvirus 6A (HHV-6A) and HHV-6B are lymphotropic viruses which replicate
      in cultured activated cord blood mononuclear cells (CBMCs) and in T-cell lines.
      Viral genomes are composed of 143-kb unique (U) sequences flanked by
      approximately 8- to 10-kb left and right direct repeats, DR(L) and DR(R). We have
      recently cloned HHV-6A (U1102) into bacterial artificial chromosome (BAC)
      vectors, employing DNA replicative intermediates. Surprisingly, HHV-6A BACs and
      their parental DNAs were found to contain short approximately 2.7-kb DRs. To test
      whether DR shortening occurred during passaging in CBMCs or in the SupT1 T-cell
      line, we compared packaged DNAs from various passages. Restriction enzymes, PCR,
      and sequencing analyses have shown the following. (i) Early (1992) viral
      preparations from CBMCs contained approximately 8-kb DRs. (ii) Viruses currently
      propagated in SupT1 cells contained approximately 2.7-kb DRs. (iii) The deletion
      spans positions 60 to 5545 in DR(L), including genes encoded by DR1 through the
      first exon of DR6. The pac-2-pac-1 packaging signals, the DR7 open reading frame
      (ORF), and the DR6 second exon were not deleted. (iv) The DR(R) sequence was
      similarly shortened by 5.4 kb. (v) The DR1 through DR6 first exon sequences were
      deleted from the entire HHV-6A BACs, revealing that they were not translocated
      into other genome locations. (vi) When virus initially cultured in CBMCs was
      passaged in SupT1 cells no DR shortening occurred. (vii) Viral stocks possessing
      short DRs replicated efficiently, revealing the plasticity of herpesvirus
      genomes. We conclude that the DR deletion occurred once, producing virus with
      advantageous growth "conquering" the population. The DR1 gene and the first DR6
      exon are not required for propagation in culture.

PMID- 20053743
TI  - Characterization of a single-cycle rabies virus-based vaccine vector.
AB  - Recombinant rabies virus (RV)-based vectors have demonstrated their efficacy in
      generating long-term, antigen-specific immune responses in murine and monkey
      models. However, replication-competent viral vectors pose significant safety
      concerns due to vector pathogenicity. RV pathogenicity is largely attributed to
      its glycoprotein (RV-G), which facilitates the attachment and entry of RV into
      host cells. We have developed a live, single-cycle RV by deletion of the G gene
      from an RV vaccine vector expressing HIV-1 Gag (SPBN-DeltaG-Gag). Passage of SPBN
      DeltaG-Gag on cells stably expressing RV-G allowed efficient propagation of the G
      deleted RV. The in vivo immunogenicity data comparing single-cycle RV to a
      replication-competent control (BNSP-Gag) showed lower RV-specific antibodies;
      however, the overall isotype profiles (IgG2a/IgG1) were similar for the two
      vaccine vectors. Despite this difference, mice immunized with SPBN-DeltaG-Gag and
      BNSP-Gag mounted similar levels of Gag-specific CD8(+) T-cell responses as
      measured by major histocompatibility complex class I Gag-tetramer staining, gamma
      interferon-enzyme-linked immunospot assay, and cytotoxic T-cell assay. Moreover,
      these cellular responses were maintained equally at immunization titers as low as
      10(3) focus-forming units for both RV vaccine vectors. CD8(+) T-cell responses
      were significantly enhanced by a boost with a single-cycle RV complemented with a
      heterologous vesicular stomatitis virus glycoprotein. These findings demonstrate
      that single-cycle RV is an effective alternative to replication-competent RV
      vectors for future development of vaccines for HIV-1 and other infectious
      diseases.

PMID- 20053744
TI  - The hepatitis B virus X protein modulates hepatocyte proliferation pathways to
      stimulate viral replication.
AB  - Worldwide, there are over 350 million people who are chronically infected with
      the human hepatitis B virus (HBV); chronic HBV infections are associated with the
      development of hepatocellular carcinoma (HCC). The results of various studies
      suggest that the HBV X protein (HBx) has a role in the development of HBV
      associated HCC. HBx can regulate numerous cellular signal transduction pathways,
      including those that modulate cell proliferation. Many previous studies that
      analyzed the impact of HBx on cell proliferation pathways were conducted using
      established or immortalized cell lines, and when HBx was expressed in the absence
      of HBV replication, and the precise effect of HBx on these pathways has often
      differed depending on experimental conditions. We have studied the effect of HBx
      on cell proliferation in cultured primary rat hepatocytes, a biologically
      relevant system. We demonstrate that HBx, both by itself and in the context of
      HBV replication, affected the levels and activities of various cell cycle
      regulatory proteins to induce normally quiescent hepatocytes to enter the G(1)
      phase of the cell cycle but not to proceed to S phase. We linked HBx regulation
      of cell proliferation to cytosolic calcium signaling and HBx stimulation of HBV
      replication. Cumulatively, our studies suggest that HBx induces normally
      quiescent hepatocytes to enter the G(1) phase of the cell cycle and that this
      calcium-dependent HBx activity is required for HBV replication. These studies
      identify an essential function of HBx during HBV replication and a mechanism that
      may connect HBV infections to the development of HCC.

PMID- 20053745
TI  - Functional analysis of RNA structures present at the 3' extremity of the murine
      norovirus genome: the variable polypyrimidine tract plays a role in viral
      virulence.
AB  - Interactions of host cell factors with RNA sequences and structures in the
      genomes of positive-strand RNA viruses play various roles in the life cycles of
      these viruses. Our understanding of the functional RNA elements present in
      norovirus genomes to date has been limited largely to in vitro analysis. However,
      we recently used reverse genetics to identify evolutionarily conserved RNA
      structures and sequences required for norovirus replication. We have now
      undertaken a more detailed analysis of RNA structures present at the 3' extremity
      of the murine norovirus (MNV) genome. Biochemical data indicate the presence of
      three stable stem-loops, including two in the untranslated region, and a single
      stranded polypyrimidine tract [p(Y)] of variable length between MNV isolates,
      within the terminal stem-loop structure. The well-characterized host cell
      pyrimidine binding proteins PTB and PCBP bound the 3'-untranslated region via an
      interaction with this variable sequence. Viruses lacking the p(Y) tract were
      viable both in cell culture and upon mouse infection, demonstrating that this
      interaction was not essential for virus replication. However, competition
      analysis with wild-type MNV in cell culture indicated that the loss of the p(Y)
      tract was associated with a fitness cost. Furthermore, a p(Y)-deleted mutant
      showed a reduction in virulence in the STAT1(-/-) mouse model, highlighting the
      role of RNA structures in norovirus pathogenesis. This work highlights how, like
      with other positive-strand RNA viruses, RNA structures present at the termini of
      the norovirus genome play important roles in virus replication and virulence.

PMID- 20053747
TI  - In vitro synthesis of Sindbis virus genomic and subgenomic RNAs: influence of
      nsP4 mutations and nucleoside triphosphate concentrations.
AB  - Two positive-strand mRNAs are made in Sindbis virus-infected cells, the genomic
      (G) RNA and the subgenomic (SG) RNA. In mosquito cells infected with wild-type
      (wt) Sindbis virus, the latter is made in excess over the former; however, in
      cells infected with SVpzf or SVcpc more G RNA is made than SG RNA. Use was made
      of in vitro systems to investigate the effects of the SVpzf and SVcpc mutations
      on the synthesis of SG and G RNAs. Our findings indicate that under standard
      reaction conditions, the SG/G RNA ratio in vitro reflects the ratio of SG to G
      RNA made in infected mosquito cells. We observed further that the RNA patterns
      seen in vitro are affected not only by the SVpzf and SVcpc mutations but also by
      the nucleoside triphosphate concentrations in the reaction mixtures and that
      introduction of these mutations into nsP4 and the promoter/template change the
      relative amounts of SG and G RNAs that are made, likely through the choice of
      promoter. We conclude that with respect to the SVpzf and SVcpc mutations, it is
      mainly the nucleotide changes in the SG promoter, not the amino acid changes in
      nsP4, that determine the SG/G RNA ratio that results. Further, it was observed
      that the SVpzf mutations enhance the in vitro synthesis of SG RNA at the lowest
      concentrations of UTP/CTP and that the single SVcpc mutation enhances the
      synthesis of G RNA at the lowest concentrations of CTP tested. We also identified
      three Arg residues in nsP4, R545, R546, and R547, that are needed for the
      synthesis of G RNA but not SG RNA.

PMID- 20053746
TI  - Adenovirus type 5 E1A and E6 proteins of low-risk cutaneous beta-human
      papillomaviruses suppress cell transformation through interaction with FOXK1/K2
      transcription factors.
AB  - The adenovirus (Adv) oncoprotein E1A stimulates cell proliferation and inhibits
      differentiation. These activities are primarily linked to the N-terminal region
      (exon 1) of E1A, which interacts with multiple cellular protein complexes. The C
      terminus (exon 2) of E1A antagonizes these processes, mediated in part through
      interaction with C-terminal binding proteins 1 and 2 (CtBP1/2). To identify
      additional cellular E1A targets that are involved in the modulation of E1A C
      terminus-mediated activities, we undertook tandem affinity purification of E1A
      associated proteins. Through mass spectrometric analysis, we identified several
      known E1A-interacting proteins as well as novel E1A targets, such as the forkhead
      transcription factors, FOXK1/K2. We identified a Ser/Thr-containing sequence
      motif in E1A that mediated interaction with FOXK1/K2. We demonstrated that the E6
      proteins of two beta-human papillomaviruses (HPV14 and HPV21) associated with
      epidermodysplasia verruciformis also interacted with FOXK1/K2 through a motif
      similar to that of E1A. The E1A mutants deficient in interaction with FOXK1/K2
      induced enhanced cell proliferation and oncogenic transformation. The
      hypertransforming activity of the mutant E1A was suppressed by HPV21 E6. An E1A
      E6 chimeric protein containing the Ser/Thr domain of the E6 protein in E1A
      interacted efficiently with FOXK1/K2 and inhibited cell transformation. Our
      results suggest that targeting FOXK1/K2 may be a common mechanism for certain
      beta-HPVs and Adv5. E1A exon 2 mutants deficient in interaction with the dual
      specificity kinases DYRK1A/1B and their cofactor HAN11 also induced increased
      cell proliferation and transformation. Our results suggest that the E1A C
      terminal region may suppress cell proliferation and oncogenic transformation
      through interaction with three different cellular protein complexes: FOXK1/K2,
      DYRK(1A/1B)/HAN11, and CtBP1/2.

PMID- 20053748
TI  - Prophylactic administration of bacterially derived immunomodulators improves the
      outcome of influenza virus infection in a murine model.
AB  - Prophylactic or therapeutic immunomodulation is an antigen-independent strategy
      that induces nonspecific immune system activation, thereby enhancing host defense
      to disease. In this study, we investigated the effect of prophylactic
      immunomodulation on the outcome of influenza virus infection using three
      bacterially derived immune-enhancing agents known for promoting distinct
      immunological profiles. BALB/c mice were treated nasally with either cholera
      toxin (CT), a mutant form of the CT-related Escherichia coli heat-labile
      enterotoxin designated LT(R192G), or CpG oligodeoxynucleotide. Mice were
      subsequently challenged with a lethal dose of influenza A/PR/8/34 virus 24 h
      after the last immunomodulation treatment and either monitored for survival or
      sacrificed postchallenge for viral and immunological analysis. Treatment with the
      three immunomodulators prevented or delayed mortality and weight loss, but only
      CT and LT(R192G) significantly reduced initial lung viral loads as measured by
      plaque assay. Analysis performed 4 days postinfection indicated that prophylactic
      treatments with CT, LT(R192G), or CpG resulted in significantly increased numbers
      of CD4 T cells, B cells, and dendritic cells and altered costimulatory marker
      expression in the airways of infected mice, coinciding with reduced expression of
      pulmonary chemokines and the appearance of inducible bronchus-associated lymphoid
      tissue-like structures in the lungs. Collectively, these results suggest that,
      despite different immunomodulatory mechanisms, CT, LT(R192G), and CpG induce an
      initial inflammatory process and enhance the immune response to primary influenza
      virus challenge while preventing potentially damaging chemokine expression. These
      studies provide insight into the immunological parameters and immune modulation
      strategies that have the potential to enhance the nonspecific host response to
      influenza virus infection.

PMID- 20053749
TI  - Breadth of neutralizing antibodies elicited by stable, homogeneous clade A and
      clade C HIV-1 gp140 envelope trimers in guinea pigs.
AB  - The native envelope (Env) spike on the surface of human immunodeficiency virus
      type 1 (HIV-1) is trimeric, and thus trimeric Env vaccine immunogens are
      currently being explored in preclinical immunogenicity studies. Key challenges
      have included the production and purification of biochemically homogeneous and
      stable trimers and the evaluation of these immunogens utilizing standardized
      virus panels for neutralization assays. Here we report the binding and
      neutralizing antibody (NAb) responses elicited by clade A (92UG037.8) and clade C
      (CZA97.012) Env gp140 trimer immunogens in guinea pigs. These trimers have been
      selected and engineered for optimal biochemical stability and have defined
      antigenic properties. Purified gp140 trimers with Ribi adjuvant elicited potent,
      cross-clade NAb responses against tier 1 viruses as well as detectable but low
      titer NAb responses against select tier 2 viruses from clades A, B, and C. In
      particular, the clade C trimer elicited NAbs that neutralized 27%, 20%, and 47%
      of tier 2 viruses from clades A, B, and C, respectively. Heterologous DNA prime,
      protein boost as well as DNA prime, recombinant adenovirus boost regimens
      expressing these antigens, however, did not result in an increased magnitude or
      breadth of NAb responses in this system. These data demonstrate the
      immunogenicity of stable, homogeneous clade A and clade C gp140 trimers and
      exemplify the utility of standardized tier 1 and tier 2 virus panels for
      assessing the NAb responses of candidate HIV-1 Env immunogens.

PMID- 20053750
TI  - N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin
      neuraminidase masks a second receptor-binding site.
AB  - The hemagglutinin-neuraminidase (HN) glycoprotein plays a critical role in
      parainfluenza virus replication. We recently found that in addition to the
      catalytic binding site, HN of human parainfluenza virus type 1 (hPIV-1) may have
      a second receptor-binding site covered by an N-linked glycan at residue 173,
      which is near the region of the second receptor-binding site identified in
      Newcastle disease virus (NDV) HN (I. A. Alymova, G. Taylor, V. P. Mishin, M.
      Watanabe, K. G. Murti, K. Boyd, P. Chand, Y. S. Babu, and A. Portner, J. Virol.
      82:8400-8410, 2008). Sequence analysis and superposition of the NDV and hPIV-3 HN
      dimer structures revealed that, similar to what was seen in hPIV-1, the N-linked
      glycan at residue 523 on hPIV-3 HN may cover a second receptor-binding site.
      Removal of this N-linked glycosylation site by an Asn-to-Asp substitution at
      residue 523 (N523D) changed the spectrum of the mutant virus's receptor
      specificity, delayed its elution from both turkey and chicken red blood cells,
      reduced mutant sensitivity (by about half) to the selective HN inhibitor BCX 2855
      in hemagglutination inhibition tests, and slowed its growth in LLC-MK(2) cells.
      The neuraminidase activity of the mutant and its sensitivity to BCX 2855 in
      neuraminidase inhibition assays did not change, indicating that the mutation did
      not affect the virus's catalytic-binding site and that all observed effects were
      caused by the exposure of the purported second receptor-binding site. Our data
      are consistent with the idea that, similar to the case for hPIV-1, the N-linked
      glycan shields a second receptor-binding site on hPIV-3 HN.

PMID- 20053751
TI  - No increase in hepatitis B virus (HBV)-specific CD8+ T cells in patients with HIV
      1-HBV coinfections following HBV-active highly active antiretroviral therapy.
AB  - Following treatment of hepatitis B virus (HBV) monoinfection, HBV-specific T-cell
      responses increase significantly; however, little is known about the recovery of
      HBV-specific T-cell responses following HBV-active highly active antiretroviral
      therapy (HAART) in HIV-HBV coinfected patients. HIV-HBV coinfected patients who
      were treatment naive and initiating HBV-active HAART were recruited as part of a
      prospective cohort study in Thailand and followed for 48 weeks (n = 24).
      Production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF
      alpha) in both HBV- and HIV-specific CD8(+) T cells was quantified using
      intracellular cytokine staining on whole blood. Following HBV-active HAART, the
      median (interquartile range) log decline from week 0 to week 48 for HBV DNA was
      5.8 log (range, 3.4 to 6.7) IU/ml, and for HIV RNA it was 3.1 (range, 2.9 to 3.5)
      log copies/ml (P < 0.001 for both). The frequency of HIV Gag-specific CD8(+) T
      cell responses significantly decreased (IFN-gamma, P < 0.001; TNF-alpha, P =
      0.05). In contrast, there was no significant change in the frequency (IFN-gamma,
      P = 0.21; TNF-alpha, P = 0.61; and IFN-gamma and TNF-alpha, P = 0.11) or
      magnitude (IFN-gamma, P = 0.13; TNF-alpha, P = 0.13; and IFN-gamma and TNF-alpha,
      P = 0.13) of HBV-specific CD8(+) T-cell responses over 48 weeks of HBV-active
      HAART. Of the 14 individuals who were HBV e antigen (HBeAg) positive, 5/14 (36%)
      lost HBeAg during the 48 weeks of follow-up. HBV-specific CD8(+) T cells were
      detected in 4/5 (80%) of patients prior to HBeAg loss. Results from this study
      show no sustained change in the HBV-specific CD8(+) T-cell response following HBV
      active HAART. These findings may have implications for the duration of treatment
      of HBV in HIV-HBV coinfected patients, particularly in HBeAg-positive disease.

PMID- 20053752
TI  - Psychopaths know right from wrong but don't care.
AB  - Adult psychopaths have deficits in emotional processing and inhibitory control,
      engage in morally inappropriate behavior, and generally fail to distinguish moral
      from conventional violations. These observations, together with a dominant
      tradition in the discipline which sees emotional processes as causally necessary
      for moral judgment, have led to the conclusion that psychopaths lack an
      understanding of moral rights and wrongs. We test an alternative explanation:
      psychopaths have normal understanding of right and wrong, but abnormal regulation
      of morally appropriate behavior. We presented psychopaths with moral dilemmas,
      contrasting their judgments with age- and sex-matched (i) healthy subjects and
      (ii) non-psychopathic, delinquents. Subjects in each group judged cases of
      personal harms (i.e. requiring physical contact) as less permissible than
      impersonal harms, even though both types of harms led to utilitarian gains.
      Importantly, however, psychopaths' pattern of judgments on different dilemmas was
      the same as those of the other subjects. These results force a rejection of the
      strong hypothesis that emotional processes are causally necessary for judgments
      of moral dilemmas, suggesting instead that psychopaths understand the distinction
      between right and wrong, but do not care about such knowledge, or the
      consequences that ensue from their morally inappropriate behavior.

PMID- 20053753
TI  - BCR-ABL enhances differentiation of long-term repopulating hematopoietic stem
      cells.
AB  - In a previously developed inducible transgenic mouse model of chronic myeloid
      leukemia, we now demonstrate that the disease is transplantable using BCR-ABL(+)
      Lin(-)Sca-1(+)c-kit(+) (LSK) cells. Interestingly, the phenotype is more severe
      when unfractionated bone marrow cells are transplanted, yet neither progenitor
      cells (Lin(-)Sca-1(-)c-kit(+)), nor mature granulocytes (CD11b(+)Gr-1(+)), nor
      potential stem cell niche cells (CD45(-)Ter119(-)) are able to transmit the
      disease or alter the phenotype. The phenotype is largely independent of BCR-ABL
      priming before transplantation. However, prolonged BCR-ABL expression abrogates
      the potential of LSK cells to induce full-blown disease in secondary recipients
      and increases the fraction of multipotent progenitor cells at the expense of long
      term hematopoietic stem cells (LT-HSCs) in the bone marrow. BCR-ABL alters the
      expression of genes involved in proliferation, survival, and hematopoietic
      development, probably contributing to the reduced LT-HSC frequency within BCR
      ABL(+) LSK cells. Reversion of BCR-ABL, or treatment with imatinib, eradicates
      mature cells, whereas leukemic stem cells persist, giving rise to relapsed
      chronic myeloid leukemia on reinduction of BCR-ABL, or imatinib withdrawal. Our
      results suggest that BCR-ABL induces differentiation of LT-HSCs and decreases
      their self-renewal capacity.

PMID- 20053754
TI  - Antibodies specifically target AML antigen NuSAP1 after allogeneic bone marrow
      transplantation.
AB  - Identifying the targets of immune response after allogeneic hematopoietic cell
      transplantation (HCT) promises to provide relevant immune therapy candidate
      proteins. We used protein microarrays to serologically identify nucleolar and
      spindle-associated protein 1 (NuSAP1) and chromatin assembly factor 1, subunit B
      (p60; CHAF1b) as targets of new antibody responses that developed after
      allogeneic HCT. Western blots and enzyme-linked immunosorbent assays (ELISA)
      validated their post-HCT recognition and enabled ELISA testing of 120 other
      patients with various malignancies who underwent allo-HCT. CHAF1b-specific
      antibodies were predominantly detected in patients with acute myeloid leukemia
      (AML), whereas NuSAP1-specific antibodies were exclusively detected in patients
      with AML 1 year after transplantation (P < .001). Complete genomic exon
      sequencing failed to identify a nonsynonymous single nucleotide polymorphism
      (SNP) for NuSAP1 and CHAF1b between the donor and recipient cells. Expression
      profiles and reverse transcriptase-polymerase chain reaction (RT-PCR) showed
      NuSAP1 was predominately expressed in the bone marrow CD34(+)CD90(+)
      hematopoietic stem cells, leukemic cell lines, and B lymphoblasts compared with
      other tissues or cells. Thus, NuSAP1 is recognized as an immunogenic antigen in
      65% of patients with AML following allogeneic HCT and suggests a tumor antigen
      role.

PMID- 20053755
TI  - Antihepcidin antibody treatment modulates iron metabolism and is effective in a
      mouse model of inflammation-induced anemia.
AB  - Iron maldistribution has been implicated in multiple diseases, including the
      anemia of inflammation (AI), atherosclerosis, diabetes, and neurodegenerative
      disorders. Iron metabolism is controlled by hepcidin, a 25-amino acid peptide.
      Hepcidin is induced by inflammation, causes iron to be sequestered, and thus,
      potentially contributes to AI. Human hepcidin (hHepc) overexpression in mice
      caused an iron-deficient phenotype, including stunted growth, hair loss, and iron
      deficient erythropoiesis. It also caused resistance to supraphysiologic levels of
      erythropoiesis-stimulating agent, supporting the hypothesis that hepcidin may
      influence response to treatment in AI. To explore the role of hepcidin in
      inflammatory anemia, a mouse AI model was developed with heat-killed Brucella
      abortus treatment. Suppression of hepcidin mRNA was a successful anemia treatment
      in this model. High-affinity antibodies specific for hHepc were generated, and
      hHepc knock-in mice were produced to enable antibody testing. Antibody treatment
      neutralized hHepc in vitro and in vivo and facilitated anemia treatment in hHepc
      knock-in mice with AI. These data indicate that antihepcidin antibodies may be an
      effective treatment for patients with inflammatory anemia. The ability to
      manipulate iron metabolism in vivo may also allow investigation of the role of
      iron in a number of other pathologic conditions.

PMID- 20053756
TI  - Classical and/or alternative NF-kappaB pathway activation in multiple myeloma.
AB  - Mutations involving the nuclear factor-kappaB (NF-kappaB) pathway are present in
      at least 17% of multiple myeloma (MM) tumors and 40% of MM cell lines (MMCLs).
      These mutations, which are apparent progression events, enable MM tumors to
      become less dependent on bone marrow signals that activate NF-kappaB. Studies on
      a panel of 51 MMCLs provide some clarification of the mechanisms through which
      these mutations act and the significance of classical versus alternative
      activation of NF-kappaB. First, only one mutation (NFKB2) selectively activates
      the alternative pathway, whereas several mutations (CYLD, NFKB1, and TACI)
      selectively activate the classical pathway. However, most mutations affecting NF
      kappaB-inducing kinase (NIK) levels (NIK, TRAF2, TRAF3, cIAP1&2, and CD40)
      activate the alternative but often both pathways. Second, we confirm the critical
      role of TRAF2 in regulating NIK degradation, whereas TRAF3 enhances but is not
      essential for cIAP1/2-mediated proteasomal degradation of NIK in MM. Third, using
      transfection to selectively activate the classical or alternative NF-kappaB
      pathways, we show virtually identical changes in gene expression in one MMCL,
      whereas the changes are similar albeit nonidentical in a second MMCL. Our results
      suggest that MM tumors can achieve increased autonomy from the bone marrow
      microenvironment by mutations that activate either NF-kappaB pathway.

PMID- 20053757
TI  - 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Src-mediated Egr
      1-dependent rapid induction of FGF-2 expression.
AB  - To understand the mechanisms underlying 15(S)-hydroxyeicosatetraenoic acid [15(S)
      HETE]-induced angiogenesis, we studied the role of Egr-1. 15(S)-HETE induced Egr
      1 expression in a time-dependent manner in human dermal microvascular endothelial
      cells (HDMVECs). Blockade of Egr-1 via forced expression of its dominant-negative
      mutant attenuated 15(S)-HETE-induced HDMVEC migration and tube formation as well
      as Matrigel plug angiogenesis. 15(S)-HETE-induced Egr-1 expression requires Src
      activation. In addition, adenovirus-mediated expression of dominant-negative
      mutant of Src blocked 15(S)-HETE's effects on migration and tube formation of
      HDMVECs and Matrigel plug angiogenesis. 15(S)-HETE induced fibroblast growth
      factor-2 (FGF-2) expression rapidly via Src-mediated production of Egr-1. Cloning
      and mutational analysis of FGF-2 promoter revealed that Egr-1 binding site
      proximal to transcription start site is required for 15(S)-HETE-induced FGF-2
      expression. Neutralizing antibody-mediated suppression of FGF-2 function also
      attenuated the effects of 15(S)-HETE on HDMVEC migration and tube formation as
      well as Matrigel plug angiogenesis. Furthermore, in contrast to wild-type mice,
      12/15-LOX(-/-) mice exhibited decreased Matrigel plug angiogenesis in response to
      AA, which was rescued by 15(S)-HETE. On the basis of these observations, we
      conclude that 15(S)-HETE-induced angiogenesis requires Src-mediated Egr-1
      dependent rapid induction of FGF-2. These findings may suggest that 15(S)-HETE
      could be a potential endogenous regulator of pathologic angiogenesis associated
      with atherosclerosis and restenosis.

PMID- 20053758
TI  - Leukemia-initiating cells from some acute myeloid leukemia patients with mutated
      nucleophosmin reside in the CD34(-) fraction.
AB  - Leukemia-initiating cells (LICs) in acute myeloid leukemia (AML) are believed to
      be restricted to the CD34(+) fraction. However, one of the most frequently
      mutated genes in AML is nucleophosmin (NPM), and this is associated with low CD34
      expression. We, therefore, investigated whether NPM-mutated AMLs have LICs
      restricted to the CD34(+) fraction. We transplanted sorted fractions of primary
      NPM-mutated AML into immunodeficient mice to establish which fractions initiate
      leukemia. Approximately one-half of cases had LICs exclusively within the CD34(-)
      fraction, whereas the CD34(+) fraction contained normal multilineage
      hematopoietic repopulating cells. Most of the remaining cases had LICs in both
      CD34(+) and CD34(-) fractions. When samples were sorted based on CD34 and CD38
      expression, multiple fractions initiated leukemia in primary and secondary
      recipients. The data indicate that the phenotype of LICs is more heterogeneous
      than previously realized and can vary even within a single sample. This feature
      of LICs may make them particularly difficult to eradicate using therapies
      targeted against surface antigens.

PMID- 20053759
TI  - The HDAC inhibitors trichostatin A and suberoylanilide hydroxamic acid exhibit
      multiple modalities of benefit for the vascular pathobiology of sickle transgenic
      mice.
AB  - The vascular pathobiology of sickle cell anemia involves inflammation,
      coagulation, vascular stasis, reperfusion injury, iron-based oxidative
      biochemistry, deficient nitric oxide (NO) bioavailability, and red cell sickling.
      These disparate pathobiologies intersect and overlap, so it is probable that
      multimodality therapy will be necessary for this disease. We have, therefore,
      tested a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), for efficacy
      in reducing endothelial activation. We found that pulmonary vascular endothelial
      VCAM-1 and tissue factor (TF) expression (both are indicators of endothelial
      activation) are powerfully and significantly inhibited by TSA. This is seen both
      with pretreatment before the inducing stress of hypoxia/reoxygenation (NY1DD
      sickle transgenic mouse), and upon longer-term therapy after endothelial
      activation has already occurred (hBERK1 sickle mouse at ambient air). In
      addition, TSA prevented vascular stasis in sickle mice, it exhibited activity as
      an iron chelator, and it induced expression of the antisickling hemoglobin,
      hemoglobin F. Notably, the TSA analog SAHA (suberoylanilide hydroxaminc acid)
      that is already approved for human clinical use exhibits the same spectrum of
      biologic effects as TSA. We suggest that SAHA possibly could provide true,
      multimodality, salubrious effects for prevention and treatment of the chronic
      vasculopathy of sickle cell anemia.

PMID- 20053760
TI  - Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: a
      multidisciplinary case presentation from the Joan Karnell cancer center of
      Pennsylvania Hospital.
AB  - The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic
      adrenocorticotropic hormone production is presented, including the workup and
      management of this uncommon complication of an uncommon disease.

PMID- 20053761
TI  - Overexpression of EpCAM in uterine serous papillary carcinoma: implications for
      EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201).
AB  - We evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the
      potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in
      uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real
      time PCR and immunohistochemistry in a total of 56 USPC fresh-frozen biopsies and
      paraffin-embedded tissues. EpCAM surface expression was also evaluated by flow
      cytometry and immunohistochemistry in six USPC cell lines. Sensitivity to MT201
      antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity
      was tested against a panel of primary USPC cell lines expressing different levels
      of EpCAM in standard 5-h (51)Cr release assays. EpCAM transcript was
      significantly overexpressed in fresh-frozen USPC when compared with normal
      endometrial cells (NEC). Median (minimum-maximum) copy number was 943.8 (31.5
      1568.3) in tumor samples versus 12.9 (1.0-37.0) in NEC (P < 0.001). By
      immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC
      samples with significantly higher expression compared with NECs (P < 0.001). High
      surface expression of EpCAM was found in 83% (five out of six) of the USPC cell
      lines tested by flow cytometry. EpCAM-positive cell lines were found highly
      sensitive to MT201-mediated antibody-dependent cellular cytotoxicity in vitro,
      whereas primary USPC cell lines were resistant to natural killer cell-dependent
      cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated
      cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma
      at mRNA and protein levels, and primary USPC are highly sensitivity to MT201
      mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in
      patients harboring advanced/recurrent or metastatic USPC refractory to standard
      treatment modalities.

PMID- 20053762
TI  - The preclinical pharmacology and therapeutic activity of the novel CHK1 inhibitor
      SAR-020106.
AB  - Genotoxic antitumor agents continue to be the mainstay of current cancer
      chemotherapy. These drugs cause DNA damage and activate numerous cell cycle
      checkpoints facilitating DNA repair and the maintenance of genomic integrity.
      Most human tumors lack functional p53 and consequently have compromised G(1)-S
      checkpoint control. This has led to the hypothesis that S and G(2)-M checkpoint
      abrogation may selectively enhance genotoxic cell killing in a p53-deficient
      background, as normal cells would be rescued at the G(1)-S checkpoint. CHK1 is a
      serine/threonine kinase associated with DNA damage-linked S and G(2)-M checkpoint
      control. SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor
      with an IC(50) of 13.3 nmol/L on the isolated human enzyme. This compound
      abrogates an etoposide-induced G(2) arrest with an IC(50) of 55 nmol/L in HT29
      cells, and significantly enhances the cell killing of gemcitabine and SN38 by 3.0
      to 29-fold in several colon tumor lines in vitro and in a p53-dependent fashion.
      Biomarker studies have shown that SAR-020106 inhibits cytotoxic drug-induced
      autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15
      in a dose-dependent fashion both in vitro and in vivo. Cytotoxic drug
      combinations were associated with increased gammaH2AX and poly ADP ribose
      polymerase cleavage consistent with the SAR-020106-enhanced DNA damage and tumor
      cell death. Irinotecan and gemcitabine antitumor activity was enhanced by SAR
      020106 in vivo with minimal toxicity. SAR-020106 represents a novel class of CHK1
      inhibitors that can enhance antitumor activity with selected anticancer drugs in
      vivo and may therefore have clinical utility.

PMID- 20053763
TI  - Multifactorial regulation of E-cadherin expression: an integrative study.
AB  - E-cadherin (E-cad) is an adhesion molecule associated with tumor invasion and
      metastasis. Its down-regulation is associated with poor prognosis for many
      epithelial tumor types. We have profiled E-cad in the NCI-60 cancer cell lines at
      the DNA, RNA, and protein levels using six different microarray platforms plus
      bisulfite sequencing. Here we consider the effects on E-cad expression of eight
      potential regulatory factors: E-cad promoter DNA methylation, the transcript
      levels of six transcriptional repressors (SNAI1, SNAI2, TCF3, TCF8, TWIST1, and
      ZFHX1B), and E-cad DNA copy number. Combined bioinformatic and pharmacological
      analyses indicate the following ranking of influence on E-cad expression: (1) E
      cad promoter methylation appears predominant, is strongly correlated with E-cad
      expression, and shows a 20% to 30% threshold above which E-cad expression is
      silenced; (2) TCF8 expression levels correlate with (-0.62) and predict (P <
      0.00001) E-cad expression; (3) SNAI2 and ZFHX1B expression levels correlate
      positively with each other (+0.83) and also correlate with (-0.32 and -0.30,
      respectively) and predict (P = 0.03 and 0.01, respectively) E-cad expression; (4)
      TWIST1 correlates with (-0.34) but does not predict E-cad expression; and (5)
      SNAI1 expression, TCF3 expression, and E-cad DNA copy number do not correlate
      with or predict E-cad expression. Predictions of E-cad regulation based on the
      above factors were tested and verified by demethylation studies using 5-aza-2'
      deoxycytidine treatment; siRNA knock-down of TCF8, SNAI2, or ZFHX1B expression;
      and combined treatment with 5-aza-2'-deoxycytidine and TCF8 siRNA. Finally,
      levels of cellular E-cad expression are associated with levels of cell-cell
      adhesion and response to drug treatment.

PMID- 20053764
TI  - Sensitivity to the aromatase inhibitor letrozole is prolonged after a "break" in
      treatment.
AB  - Using a hormone-dependent xenograft model, we established that loss of response
      to letrozole was accompanied by upregulation of the Her-2/mitogen-activated
      protein kinase (MAPK) pathway and downregulation of estrogen receptor alpha
      (ERalpha) and aromatase activity. In our previous study, we showed that stopping
      letrozole treatment or adding trastuzumab could reverse acquired resistance. In
      this study, we compared the effects of intermittent letrozole treatment and
      switching treatment between letrozole and trastuzumab on tumor growth in an
      attempt to optimize discontinuous letrozole treatment. The mice were treated with
      letrozole until the tumors developed resistance and then were divided into three
      groups: (a) letrozole, (b) trastuzumab, and (c) "off" (Delta(4)A supplement
      only); tumors were collected every week to examine changes in tumor protein
      expression and activity. In off group tumors, Her-2/p-MAPK activation gradually
      decreased and ERalpha and aromatase protein (and activity) increased. Within the
      first week of trastuzumab treatment, Her-2 and MAPK were downregulated and
      ERalpha was upregulated. When letrozole-resistant MCF-7Ca tumors were taken off
      treatment for 4 weeks, the second course of letrozole treatment provided a much
      longer duration of response (P = 0.02). However, switching treatment to
      trastuzumab for 4 weeks did not provide any inhibition of tumor growth. Our
      studies revealed that the adaptation of cells to a low-estrogen environment by
      upregulation of Her-2/MAPK and downregulation of ERalpha/aromatase was reversed
      on letrozole withdrawal. The tumors once again became responsive to letrozole for
      a significant period. These results suggest that response to letrozole can be
      prolonged by a short "break" in the treatment.

PMID- 20053765
TI  - 8-Amino-adenosine inhibits multiple mechanisms of transcription.
AB  - Roscovitine and flavopiridol suppress cyclin-dependent kinase 7 (CDK7) and CDK9
      activity resulting in transcription inhibition, thus providing an alternative
      mechanism to traditional genotoxic chemotherapy. These agents have been effective
      in slow or nonreplicative cell types. 8-Amino-adenosine is a transcription
      inhibitor that has proved very effective in multiple myeloma cell lines and
      primary indolent leukemia cells. The objective of the current work was to define
      mechanisms of action that lead to transcription inhibition by 8-amino-adenosine.
      8-Amino-adenosine is metabolized into the active triphosphate (8-amino-ATP) in
      cells. This accumulation resulted in a simultaneous decrease of intracellular ATP
      and RNA synthesis. When the effects of established ATP synthesis inhibitors and
      transcription inhibitors on intracellular ATP concentrations and RNA synthesis
      were studied, there was a strong correlation between ATP decline and RNA
      synthesis. This correlation substantiated the hypothesis that the loss of ATP in
      8-amino-adenosine-treated cells contributes to the decrease in transcription due
      to the lack of substrate needed for mRNA body and polyadenylation tail synthesis.
      RNA polymerase II COOH terminal domain phosphorylation declined sharply in 8
      amino-adenosine-treated cells, which may have been due to the lack of an ATP
      phosphate donor or competitive inhibition with 8-amino-ATP at CDK7 and CDK9.
      Furthermore, 8-amino-ATP was incorporated into nascent RNA in a dose-dependent
      manner at the 3'-end resulting in transcription termination. Finally, in vitro
      transcription assays showed that 8-amino-ATP competes with ATP for incorporation
      into mRNA. Collectively, we have concluded that 8-amino-adenosine elicits effects
      on multiple mechanisms of transcription, providing a new class of transcription
      inhibitors.

PMID- 20053766
TI  - The antitumor activity of homoharringtonine against human mast cells harboring
      the KIT D816V mutation.
AB  - Gain-of-function mutations of the receptor tyrosine kinase KIT play a critical
      role in the pathogenesis of systemic mastocytosis (SM) and gastrointestinal
      stromal tumors. The various juxtamembrane type of KIT mutations, including V560G,
      are found in 60% to 70% of patients with gastrointestinal stromal tumors; loop
      mutant D816V, which exists in approximately 80% of SM patients, is completely
      resistant to imatinib. In the present study, we hypothesized that
      homoharringtonine (HHT), a protein synthesis inhibitor, would decrease the level
      of KIT protein by inhibiting translation, resulting in a decreased level of
      phospho-KIT and abrogating its constitutive downstream signaling. Imatinib
      sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain
      of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V
      mutations, and murine P815 cells were treated with HHT and analyzed in terms of
      growth, apoptosis, and signal transduction. The in vivo antitumor activity was
      evaluated by using the murine mast cell leukemia model. Our results indicated
      that HHT effectively inhibited the growth and induced apoptosis in cells bearing
      both V560G and D816V or D814Y KIT. Additionally, HHT inhibited the KIT-dependent
      phosphorylation of downstream signaling molecules Akt, signal transducer and
      activator of transcription 3 and 5, and extracellular signal-regulated kinase
      1/2. Furthermore, HHT significantly prolonged the survival duration of mice with
      aggressive SM or mast cell leukemia by inhibiting the expansion and infiltration
      of imatinib-resistant mast tumor cells harboring imatinib-resistant D814Y KIT.
      Collectively, we show that HHT circumvents D816V KIT-elicited imatinib
      resistance. Our findings warrant a clinical trial of HHT in patients with SM
      harboring D816V or D814Y KIT.

PMID- 20053768
TI  - Selective inhibition of histone deacetylases sensitizes malignant cells to death
      receptor ligands.
AB  - Evasion of death receptor ligand-induced apoptosis represents an important
      contributor to cancer development and progression. Therefore, molecules that
      restore sensitivity to death receptor stimuli would be important tools to better
      understand this biological pathway and potential leads for therapeutic adjuncts.
      Previously, the small-molecule 4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide
      (that we propose be named droxinostat) was identified as a chemical sensitizer to
      death receptor stimuli, decreasing the expression of the caspase-8 inhibitor
      FLIP. However, the direct targets of droxinostat were unknown. To better
      understand the mechanism of action of droxinostat and highlight new strategies to
      restore sensitivity to death receptor ligands, we analyzed changes in gene
      expression using the Connectivity Map after treating cells with droxinostat.
      Changes in gene expression after droxinostat treatment resembled changes observed
      after treatment with histone deacetylase (HDAC) inhibitors. Therefore, we
      examined the effects of droxinostat on HDAC activity and showed that it
      selectively inhibited HDAC3, HDAC6, and HDAC8 and that inhibition of these HDACs
      was functionally important for its ability to sensitize cells to death ligands.
      Thus, we have identified a selective HDAC inhibitor and showed that selective
      HDAC inhibition sensitizes cells to death ligands, thereby highlighting a new
      mechanism to overcome resistance to death receptor ligands.

PMID- 20053767
TI  - Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric
      Preclinical Testing Program.
AB  - Rapamycin demonstrated broad-spectrum tumor growth inhibition activity against
      the in vivo panels of childhood tumors used in the Pediatric Preclinical Testing
      Program (PPTP). Here we have evaluated rapamycin combined with agents used
      frequently in the treatment of childhood malignancies. Rapamycin was tested in
      vitro against 23 cell lines alone or in combination with melphalan, cisplatin,
      vincristine, or dexamethasone (leukemic models only). In vivo, the impact of
      combining rapamycin with a cytotoxic agent was evaluated using two measures: 1)
      the therapeutic enhancement measure, and 2) a linear regression model for time-to
      event to formally evaluate for sub- and supraadditivity for the combination
      compared to the agents used alone. Combining rapamycin with cytotoxic agents in
      vitro gave predominantly subadditive or additive effects, except for
      dexamethasone in leukemia models for which supra-additive activity was observed.
      In vivo testing demonstrated that therapeutic enhancement was common for
      rapamycin in combination with cyclophosphamide and occurred for 4 of 11 evaluable
      xenografts for the rapamycin and vincristine combination. The combinations of
      rapamycin with either cyclophosphamide or vincristine were significantly more
      effective than the respective standard agents used alone at their maximum
      tolerated doses (MTD) for most evaluable xenografts. The combination of rapamycin
      and cisplatin produced excessive toxicity requiring cisplatin dose reductions,
      and therapeutic enhancement was not observed for this combination. Addition of
      rapamycin to either cyclophosphamide or vincristine at their respective MTDs
      appears promising, as these combinations are relatively well tolerated and as
      many of the pediatric preclinical models evaluated demonstrated therapeutic
      enhancement for these combinations.

PMID- 20053769
TI  - Structure activity analysis of 2-methoxyestradiol analogues reveals targeting of
      microtubules as the major mechanism of antiproliferative and proapoptotic
      activity.
AB  - 2-Methoxyestradiol (2ME2) is an anticancer agent with antiproliferative,
      antiangiogenic, and proapoptotic effects. A major proposed mechanism of drug
      action is the disruption of the microtubule skeleton, leading to the induction of
      cell cycle arrest and apoptosis. In addition, other mechanisms of action have
      been proposed, including the generation of reactive oxygen species (ROS),
      inhibition of hypoxia-inducible factor (HIF), and interference with mitochondrial
      function. In this study, we used a selection of 2ME2 analogues to conduct
      structure activity analysis and correlated the antiproliferative and proapoptotic
      activity of the various analogues with their effects on different drug targets. A
      good correlation was observed between drug activity and effects on microtubule
      function. In contrast, our results indicate that effects on ROS, HIF, and
      mitochondria are unlikely to contribute significantly to the cellular activity of
      2ME2. Thus, our data indicate that the structural requirements for inducing ROS
      and inhibition of complex I of the mitochondrial electron transport chain were
      different from those required for proapoptotic drug activity. Furthermore,
      antioxidant treatment or overexpression of catalase did not inhibit the cellular
      activity of 2ME2 in epithelial cancer cells. Inhibition of HIF required much
      higher concentrations of 2ME2 analogues compared with concentrations that
      inhibited cell proliferation and induced apoptosis. Our results thus provide a
      better insight into the mechanism of action of 2ME2 and reveal structural
      requirements that confer high cellular activity, which may aid future drug
      development.

PMID- 20053770
TI  - Meeting report on the second targeted tumor therapies.
AB  - This meeting report on the fourth Fabisch Symposium for Cancer Research and
      Molecular Biology describes the aims of the international meeting, the main
      topics of the presentations, and the highlights of the conference. The fourth
      Fabisch Symposium was the second on Targeted Tumor Therapies and held from April
      1-3, 2009 in Berlin, Germany. The meeting focused on noncarrier-based targeted
      tumor therapies and their clinical application. The world's leading experts in
      this field presented the state of the art on tumor-specific targeting and tumor
      growth inhibition, drug design and production, and the description of innovative
      strategies for improved delivery. The topics concentrated on immunotoxins and
      other targeted toxins as anticancer drugs, thus providing a specialized meeting
      platform not existing elsewhere for these therapeutics. Although a number of
      innovative approaches on the avoidance of immune responses against highly
      effective toxins were presented, a notable conclusion of the meeting and
      direction for future research is the acute need to further reduce the
      immunogenicity of the targeted toxins, which hampers the efficacy of this group
      of therapeutics in clinical studies. The meeting successfully fostered plans for
      further research and cooperation between different groups to hopefully achieve
      advanced translational and clinical studies.

PMID- 20053771
TI  - BAMLET activates a lysosomal cell death program in cancer cells.
AB  - A complex of human alpha-lactalbumin and oleic acid (HAMLET) was originally
      isolated from human milk as a potent anticancer agent. It kills a wide range of
      transformed cells of various origins while leaving nontransformed healthy cells
      largely unaffected both in vitro and in vivo. Importantly, purified alpha
      lactalbumins from other mammals form complexes with oleic acid that show
      biological activities similar to that of HAMLET. The mechanism by which these
      protein-lipid complexes kill tumor cells is, however, largely unknown. Here, we
      show that complex of bovine alpha-lactalbumin and oleic acid (BAMLET), the bovine
      counterpart of HAMLET, kills tumor cells via a mechanism involving lysosomal
      membrane permeabilization. BAMLET shows potent cytotoxic activity against eight
      cancer cell lines tested, whereas nontransformed NIH-3T3 murine embryonic
      fibroblasts are relatively resistant. BAMLET accumulates rapidly and specifically
      in the endolysosomal compartment of tumor cells and induces an early leakage of
      lysosomal cathepsins into the cytosol followed by the activation of the
      proapoptotic protein Bax. Ectopic expression of three proteins known to stabilize
      the lysosomal compartment, i.e. heat shock protein 70 (Hsp70), Hsp70-2, and lens
      epithelium-derived growth factor, confer significant protection against BAMLET
      induced cell death, whereas the antiapoptotic protein Bcl-2, caspase inhibition,
      and autophagy inhibition fail to do so. These data indicate that BAMLET triggers
      lysosomal cell death pathway in cancer cells, thereby clarifying the ability of
      alpha-lactalbumin:oleate complexes to kill highly apoptosis-resistant tumor
      cells.

PMID- 20053772
TI  - Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector
      responses by the signal transducers and activators of transcription 3 pathway.
AB  - Glioblastoma multiforme (GBM) is a lethal cancer that responds poorly to
      radiotherapy and chemotherapy. Glioma cancer-initiating cells have been shown to
      recapitulate the characteristic features of GBM and mediate chemotherapy and
      radiation resistance. However, it is unknown whether the cancer-initiating cells
      contribute to the profound immune suppression in GBM patients. Recent studies
      have found that the activated form of signal transducer and activator of
      transcription 3 (STAT3) is a key mediator in GBM immunosuppression. We isolated
      and generated CD133+ cancer-initiating single colonies from GBM patients and
      investigated their immune-suppressive properties. We found that the cancer
      initiating cells inhibited T-cell proliferation and activation, induced
      regulatory T cells, and triggered T-cell apoptosis. The STAT3 pathway is
      constitutively active in these clones and the immunosuppressive properties were
      markedly diminished when the STAT3 pathway was blocked in the cancer-initiating
      cells. These findings indicate that cancer-initiating cells contribute to the
      immune evasion of GBM and that blockade of the STAT3 pathway has therapeutic
      potential.

PMID- 20053773
TI  - Global methylation pattern of genes in androgen-sensitive and androgen
      independent prostate cancer cells.
AB  - Promoter DNA methylation of CpG islands is an important epigenetic mechanism in
      cancer development. We have characterized the promoter methylation profile of 82
      genes in three prostate cancer cell lines (LNCaP, PC3, and DU145) and two normal
      prostate cell lines (RWPE1 and RWPE2). The methylation pattern was analyzed using
      a Panomics gene array system that consists of immobilized probes of known gene
      promoters on a nitrocellulose membrane. Methylation binding protein-purified
      methylated DNA was hybridized on the membrane and detected by the
      chemiluminescence method. We analyzed methylation profile in normal (RWPE1)
      versus cancerous cells and androgen receptor (AR)-sensitive (LNCaP) versus AR
      negative cells (DU145 and PC3). Our study shows that >50% of the genes were
      hypermethylated in prostate cancer cells compared with 13% in normal cell lines.
      Among these were the tumor suppressor (RB, TMS1, DAPK, RBL1, PAX6, and FHIT),
      cell cycle (p27KIP1 and CDKN2A), transporters (MDR1, MLC1, and IGRP), and
      transcription factor (STAT1, CIITA, MYOD, and NPAT) genes. Relative methylation
      pattern shows that most of these genes were methylated from 5-fold to >10-fold
      compared with the normal prostate cells. In addition, promoter methylation was
      detected for the first time in target genes such as RIOK3, STAT5, CASP8, SRBC,
      GAGE1, and NPAT. A significant difference in methylation pattern was observed
      between AR-sensitive versus AR-negative cancer cells for the following genes:
      CASP8, GPC3, CD14, MGMT, IGRP, MDR1, CDKN2A, GATA3, and IFN. In summary, our
      study identified candidate genes that are methylated in prostate cancer.

PMID- 20053774
TI  - Human sodium/iodide symporter-mediated radioiodine gene therapy enhances the
      killing activities of CTLs in a mouse tumor model.
AB  - We examined whether human sodium/iodide symporter (hNIS) radioiodine gene therapy
      can modulate the phenotype of cancer cells and enhance the killing activities of
      CTLs in a mouse tumor model. Various doses of I-131 (75, 300, 600, 1,200, and
      2,400 microCi/5 mL) were incubated with hNIS-expressing colon cancer (CT26/hNIS)
      and parental cells (CT26), and numbers of MHC class I and Fas-expressing cells
      were determined by fluorescence-activated cell sorting (FACS). In addition,
      CT26/hNIS or CT26 tumor-bearing mice were treated with 1,200 microCi of I-131,
      and percentages of MHC class I and Fas-expressing tumor cells were determined by
      FACS. The levels of tumor-infiltrating CD8+IFNgamma+ and CD11c+CD86+ cells and
      CTL killing activities were measured in CT26/hNIS tumor-bearing mice (treated
      with PBS or 1,200 microCi of I-131) by FACS and lactate dehydrogenase assay,
      respectively. MHC class I and Fas gene expressions were markedly upregulated in
      CT26/hNIS cells, but not in CT26 cells, in an I-131 dose-dependent manner. The
      level of MHC class I and Fas-expressing cancer cell were 4.5-fold and 2.1-fold
      higher in CT26/hNIS tumors than in CT26 tumors, respectively (P < 0.01).
      Interestingly, numbers of tumor-infiltrating CD8+IFNgamma+ cells and CD11c+CD86+
      cells were 5-fold and 2.5-fold higher in I-131-treated tumors than in PBS tumors,
      respectively (P < 0.001). Furthermore, CTL assays showed significantly more
      specific tumor cell lysis in I-131 tumors than in PBS tumors (P < 0.01). Our
      findings suggest that hNIS radioiodine gene therapy can generate tumor-associated
      immunity in tumor microenvironments and enhance the killing activities of CTLs.

PMID- 20053775
TI  - MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity
      alone and in combination with docetaxel.
AB  - Aurora-A kinase is a one of the key regulators during mitosis progression. Aurora
      A kinase is a potential target for anticancer therapies because overexpression of
      Aurora-A, which is frequently observed in some human cancers, results in aberrant
      mitosis leading to chromosomal instability and possibly tumorigenesis. MK-5108 is
      a novel small molecule with potent inhibitory activity against Aurora-A kinase.
      Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B,
      MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase
      assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle
      arrest at the G(2)-M phase in flow cytometry analysis. The effect was confirmed
      by the accumulation of cells with expression of phosphorylated Histone H3 and
      inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also
      induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude
      rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in
      culture and in different xenograft models. Furthermore, the combination of MK
      5108 and docetaxel showed enhanced antitumor activities compared with control and
      docetaxel alone-treated animals without exacerbating the adverse effects of
      docetaxel. MK-5108 is currently tested in clinical trials and offers a new
      therapeutic approach to combat human cancers as a single agent or in combination
      with existing taxane therapies.

PMID- 20053776
TI  - A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in
      combination with VEGF inhibitors and chemotherapy agents in preclinical models.
AB  - Localized angiopoietin-2 (Ang2) expression has been shown to function as a key
      regulator of blood vessel remodeling and tumor angiogenesis, making it an
      attractive candidate for antiangiogenic therapy. A fully human monoclonal
      antibody (3.19.3) was developed, which may have significant pharmaceutical
      advantages over synthetic peptide-based approaches in terms of reduced
      immunogenicity and increased half-life to block Ang2 function. The 3.19.3
      antibody potently binds Ang2 with an equilibrium dissociation constant of 86
      pmol/L, leading to inhibition of Tie2 receptor phosphorylation in cell-based
      assays. In preclinical models, 3.19.3 treatment blocked blood vessel formation in
      Matrigel plug assays and in human tumor xenografts. In vivo studies with 3.19.3
      consistently showed broad antitumor activity as a single agent across a panel of
      diverse subcutaneous and orthotopic xenograft models. Combination studies of
      3.19.3 with cytotoxic drugs or anti-vascular endothelial growth factor agents
      showed significant improvements in antitumor activity over single-agent
      treatments alone with no apparent evidence of increased toxicity. Initial
      pharmacokinetic profiling studies in mice and nonhuman primates suggested that
      3.19.3 has a predicted human half-life of 10 to 14 days. These studies provide
      preclinical data for 3.19.3 as a potential new antiangiogenic therapy as a single
      agent or in combination with chemotherapy or vascular endothelial growth factor
      inhibitors for the treatment of cancer.

PMID- 20053777
TI  - Astrocyte elevated gene-1: a novel target for human glioma therapy.
AB  - Malignant gliomas including glioblastoma multiforme (GBM) and anaplastic
      astrocytomas are the most common primary brain tumors. Despite multimodal
      treatment including surgery, chemotherapy, and radiation, median survival for
      patients with GBMs is only 12 to 15 months. Identifying molecules critical for
      glioma progression is crucial for devising effective targeted therapy. In the
      present study, we investigated the potential contribution of astrocyte elevated
      gene-1 (AEG-1) in gliomagenesis and explored the possibility of AEG-1 as a
      therapeutic target for malignant glioma. We analyzed the expression levels of AEG
      1 in 9 normal brain tissues and 98 brain tumor patient samples by Western blot
      analysis and immunohistochemistry. AEG-1 expression was significantly elevated in
      >90% of diverse human brain tumor samples including GBMs and astrocytic tumors,
      and also in human glioma cell lines compared with normal brain tissues and normal
      astrocytes. Knockdown of AEG-1 by small interfering RNA inhibited cell viability,
      cloning efficiency, and invasive ability of U87 human glioma cells and 9L rat
      gliosarcoma cells. We also found that matrix metalloproteases (MMP-2 and MMP-9)
      are involved in AEG-1-mediated invasion of glioma cells. In an orthotopic nude
      mouse brain tumor model using primary human GBM12 tumor cells, AEG-1 small
      interfering RNA significantly suppressed glioma cell growth in vivo. Taken
      together, these provocative results indicate that AEG-1 may play a crucial role
      in the pathogenesis of glioma and that AEG-1 could represent a viable potential
      target for malignant glioma therapy.

PMID- 20053778
TI  - Inhibition of tumor angiogenesis by the matrix metalloproteinase-activated
      anthrax lethal toxin in an orthotopic model of anaplastic thyroid carcinoma.
AB  - Patients with anaplastic thyroid carcinoma (ATC) typically succumb to their
      disease months after diagnosis despite aggressive therapy. A large percentage of
      ATCs have been shown to harbor the V600E B-Raf point mutation, leading to the
      constitutive activation of the mitogen-activated protein kinase pathway. ATC
      invasion, metastasis, and angiogenesis are in part dependent on the gelatinase
      class of matrix metalloproteinases (MMP). The explicit targeting of these two
      tumor markers may provide a novel therapeutic strategy for the treatment of ATC.
      The MMP-activated anthrax lethal toxin (LeTx), a novel recombinant protein toxin
      combination, shows potent mitogen-activated protein kinase pathway inhibition in
      gelatinase-expressing V600E B-Raf tumor cells in vitro. However, preliminary in
      vivo studies showed that the MMP-activated LeTx also exhibited dramatic antitumor
      activity against xenografts that did not show significant antiproliferative
      responses to the LeTx in vitro. Here, we show that the MMP-activated LeTx
      inhibits orthotopic ATC xenograft progression in both toxin-sensitive and toxin
      resistant ATC cells via reduced endothelial cell recruitment and subsequent tumor
      vascularization. This in turn translates to an improved long-term survival that
      is comparable with that produced by the multikinase inhibitor sorafenib. Our
      results also indicate that therapy with the MMP-activated LeTx is extremely
      effective against advanced tumors with well-established vascular networks. Taken
      together, these results suggest that the MMP-activated LeTx-mediated endothelial
      cell targeting is the primary in vivo antitumor mechanism of this novel toxin.
      Therefore, the MMP-activated LeTx could be used not only in the clinical
      management of V600E B-Raf ATC but potentially in any solid tumor.

PMID- 20053779
TI  - Preclinical in vivo evaluation of efficacy, pharmacokinetics, and
      pharmacodynamics of a novel MEK1/2 kinase inhibitor RO5068760 in multiple tumor
      models.
AB  - Targeting the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular
      signal-regulated kinase (ERK) pathway represents a promising anticancer strategy.
      Recently, we have reported a novel class of potent and selective non-ATP
      competitive MEK1/2 inhibitors with a unique structure and mechanism of action.
      RO5068760 is a representative of this class showing significant efficacy in a
      broad spectrum of tumors with aberrant mitogen-activated protein kinase pathway
      activation. To understand the relationship between systemic exposures and target
      (MEK1/2) inhibition as well as tumor growth inhibition, the current study
      presents a detailed in vivo characterization of efficacy, pharmacokinetics, and
      pharmacodynamics of RO5068760 in multiple xenograft tumor models. For inhibition
      of MEK1/2 as measured by the phosphorylated ERK levels, the estimated EC(50)s in
      plasma were 1.36 micromol/L (880 ng/mL) and 3.35 micromol/L (2168 ng/mL) in LOX
      melanoma and HT-29 colorectal cancer models, respectively. A similar EC(50) (1.41
      micromol/L or 915 ng/mL) was observed in monkey peripheral blood lymphocytes. To
      achieve tumor growth inhibition (>or=90%), an average plasma drug concentration
      of 0.65 or 5.23 micromol/L was required in B-RafV600E or K-Ras mutant tumor
      models, respectively, which were remarkably similar to the IC(90) values (0.64 or
      4.1 micromol/L) determined in vitro for cellular growth inhibition. With
      equivalent in vivo systemic exposures, RO5068760 showed superior efficacy in
      tumors harboring B-RafV600E mutation. The plasma concentration time profiles
      indicate that constant p-ERK suppression (>50%) may not be required for optimal
      efficacy, especially in highly responsive tumors. This study may facilitate
      future clinical trial design in using biochemical markers for early proof of
      mechanism and in selecting the right patients and optimal dose regimen.

PMID- 20053780
TI  - Cannabidiol enhances the inhibitory effects of delta9-tetrahydrocannabinol on
      human glioblastoma cell proliferation and survival.
AB  - The cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor agonist Delta(9)
      tetrahydrocannabinol (THC) has been shown to be a broad-range inhibitor of cancer
      in culture and in vivo, and is currently being used in a clinical trial for the
      treatment of glioblastoma. It has been suggested that other plant-derived
      cannabinoids, which do not interact efficiently with CB(1) and CB(2) receptors,
      can modulate the actions of Delta(9)-THC. There are conflicting reports, however,
      as to what extent other cannabinoids can modulate Delta(9)-THC activity, and most
      importantly, it is not clear whether other cannabinoid compounds can either
      potentiate or inhibit the actions of Delta(9)-THC. We therefore tested
      cannabidiol, the second most abundant plant-derived cannabinoid, in combination
      with Delta(9)-THC. In the U251 and SF126 glioblastoma cell lines, Delta(9)-THC
      and cannabidiol acted synergistically to inhibit cell proliferation. The
      treatment of glioblastoma cells with both compounds led to significant
      modulations of the cell cycle and induction of reactive oxygen species and
      apoptosis as well as specific modulations of extracellular signal-regulated
      kinase and caspase activities. These specific changes were not observed with
      either compound individually, indicating that the signal transduction pathways
      affected by the combination treatment were unique. Our results suggest that the
      addition of cannabidiol to Delta(9)-THC may improve the overall effectiveness of
      Delta(9)-THC in the treatment of glioblastoma in cancer patients.

PMID- 20053781
TI  - The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by
      blocking Akt in cancer cells with overactivated Akt.
AB  - Aberrant activation of Akt plays a pivotal role in cancer development. ATM, a
      protein deficient in patients with ataxia-telangiectasia disease, is
      traditionally considered as a nuclear protein kinase that functions as a signal
      transducer in response to DNA damage. It has recently been shown that ATM is also
      a cytoplasmic protein that mediates the full activation of Akt in response to
      insulin. Our study shows that a specific ATM inhibitor, KU-55933, blocks the
      phosphorylation of Akt induced by insulin and insulin-like growth factor I in
      cancer cells that exhibit abnormal Akt activity. Moreover, KU-55933 inhibits
      cancer cell proliferation by inducing G(1) cell cycle arrest. It does so through
      the downregulation of the synthesis of cyclin D1, a protein known to be elevated
      in a variety of tumors. In addition, KU-55933 treatment during serum starvation
      triggers apoptosis in these cancer cells. Our results suggest that KU-55933 may
      be a novel chemotherapeutic agent targeting cancer resistant to traditional
      chemotherapy or immunotherapy due to aberrant activation of Akt. Furthermore, KU
      55933 completely abrogates rapamycin-induced feedback activation of Akt.
      Combination of KU-55933 and rapamycin not only induces apoptosis, which is not
      seen in cancer cells treated only with rapamycin, but also shows better efficacy
      in inhibiting cancer cell proliferation than each drug alone. Therefore,
      combining KU-55933 with rapamycin may provide a highly effective approach for
      improving mammalian target of rapamycin-targeted anticancer therapy that is
      currently hindered by rapamycin-induced feedback activation of Akt.

PMID- 20053782
TI  - Notch-1 inhibition by Withaferin-A: a therapeutic target against colon
      carcinogenesis.
AB  - Notch signaling plays a crucial role in the development of colon cancer;
      targeting the Notch pathway may sensitize colon cancers to various adjuvant
      agents. The focus of our current study is to identify natural compounds that
      target Notch signaling and that might be beneficial for the prevention and
      treatment of colon cancer. Withaferin-A (WA) is a bioactive compound derived from
      Withania somnifera, which inhibits Notch-1 signaling and downregulates
      prosurvival pathways, such as Akt/NF-kappaB/Bcl-2, in three colon cancer cell
      lines (HCT-116, SW-480, and SW-620). In addition, WA downregulated the expression
      of mammalian target of rapamycin signaling components, pS6K and p4E-BP1, and
      activated c-Jun-NH(2)-kinase-mediated apoptosis in colon cancer cells. We also
      established the molecular link between Notch/Akt/mammalian target of rapamycin
      signaling by complementary approaches (i.e., overexpression of Notch-1 or
      inhibition of Notch-1 by small interfering RNA). Our results suggest that WA
      inhibits Notch-mediated prosurvival signaling, which facilitates c-Jun-NH(2)
      kinase-mediated apoptosis in colon cancer cell lines. These results underscore
      the anticancer activity of WA, which exhibits potential for further development
      for targeted chemotherapy and/or chemoprevention strategies in the context of
      colon cancer.

PMID- 20053783
TI  - Disabling c-Myc in childhood medulloblastoma and atypical teratoid/rhabdoid tumor
      cells by the potent G-quadruplex interactive agent S2T1-6OTD.
AB  - We investigated here the effects of S2T1-6OTD, a novel telomestatin derivative
      that is synthesized to target G-quadruplex-forming DNA sequences, on a
      representative panel of human medulloblastoma (MB) and atypical teratoid/rhabdoid
      (AT/RT) childhood brain cancer cell lines. S2T1-6OTD proved to be a potent c-Myc
      inhibitor through its high-affinity physical interaction with the G-quadruplex
      structure in the c-Myc promoter. Treatment with S2T1-6OTD reduced the mRNA and
      protein expressions of c-Myc and hTERT, which is transcriptionally regulated by c
      Myc, and decreased the activities of both genes. In remarkable contrast to
      control cells, short-term (72-hour) treatment with S2T1-6OTD resulted in a dose-
      and time-dependent antiproliferative effect in all MB and AT/RT brain tumor cell
      lines tested (IC(50), 0.25-0.39 micromol/L). Under conditions where inhibition of
      both proliferation and c-Myc activity was observed, S2T1-6OTD treatment decreased
      the protein expression of the cell cycle activator cyclin-dependent kinase 2 and
      induced cell cycle arrest. Long-term treatment (5 weeks) with nontoxic
      concentrations of S2T1-6OTD resulted in a time-dependent (mainly c-Myc-dependent)
      telomere shortening. This was accompanied by cell growth arrest starting on day
      28 followed by cell senescence and induction of apoptosis on day 35 in all of the
      five cell lines investigated. On in vivo animal testing, S2T1-6OTD may well
      represent a novel therapeutic strategy for childhood brain tumors.

PMID- 20053784
TI  - Purification and characterization of new phytoferritin from black bean (Phaseolus
      vulgaris L.) seed.
AB  - In contrast to animal ferritin, relatively little information is available on
      phytoferritin. Black bean (Phaseolus vulgaris L.) has been consumed in many
      countries. In the present study, new ferritin from black bean seed was purified
      by two consecutive anion exchange and size exclusion chromatography. The apparent
      molecular mass of the native black bean seed ferritin (BSF) was found to be
      approximately 560 kDa by native PAGE analysis. N-terminal sequence, MALDI-TOF-MS
      and MS/MS analyses indicate that BSF and soybean seed ferritin (SSF) share very
      high identity in amino acid sequence. However, SDS-PAGE result indicates that BSF
      consists of 26.5 (H-1) and 28.0 kDa (H-2) subunits with a ratio of 2 : 1, while
      the ratio of these two subunits in SSF is 1 : 1. This result demonstrates that
      the two proteins have different subunit composition which might affect their
      activities in iron uptake and release. Indeed, at high iron flux, the initial
      rate of iron oxidative deposition in apoBSF is larger than that in apoSSF. On the
      contrary, the iron release from BSF is significantly slower than that from SSF.
      All these results indicate that phytoferritin might regulate the transit of iron
      into and out of the protein cavity by changing its subunit composition.

PMID- 20053785
TI  - Mechanical stretch enhances NF-kappaB-dependent gene expression and poly(ADP
      ribose) synthesis in synovial cells.
AB  - Temporomandibular joint disorders (TMD) show complex symptoms associated with
      inflammation, pain and degeneration of the peripheral tissues including synovium.
      Although it is believed that excessive mechanical stress on synovium causes
      development of TMD, the molecular mechanism by which mechanical stress triggers
      TMD has still remained unclear. In order to examine the effect of mechanical
      stress on synoviocytes, rabbit synovial cells were cyclically stretched in vitro.
      The stretch efficiently increased the gene expressions of cyclooxygenase-2 (COX
      2), inducible nitric oxide synthase (iNOS) and NF-kappaB responsive reporter gene
      constructs. The interruption of NF-kappaB activating pathway by inhibitors
      resulted in the abrogation of those expressions, indicating the pivotal role of
      NF-kappaB in the mechanical stretch-mediated COX-2 and iNOS expressions. In
      parallel, the stretch remarkably increased NO production and poly(ADP-ribose)
      (PAR) synthesis, suggesting that excessive amounts of NO causes DNA injury and in
      turn activates PAR synthesis by poly(ADP-ribose) polymerase (PARP). The
      inhibition of PAR synthesis by a PARP inhibitor or a radical scavenger enhanced
      the mechanical stretch-induced gene expressions in a NF-kappaB-independent
      manner, implying an involvement of PARP in the gene expression. Taken together,
      these results demonstrate that mechanical stress on synovial cells not only
      induces gene expressions of COX-2 and iNOS but also affects PAR synthesis.

PMID- 20053786
TI  - Overexpression of Sall1 in vivo leads to reduced body weight without affecting
      kidney development.
AB  - Human SALL1 is a homologue of the Drosophila region-specific homeotic gene sal,
      and is also known as a causative gene for Townes-Brocks syndrome, which is
      characterized by multi-organ malformations. We previously demonstrated that mouse
      Sall1 plays a crucial role in ureteric bud invasion during kidney development,
      and possibly in nephron progenitor cells in the metanephric mesenchyme. To gain
      insights into the Sall1 functions in the kidney and other tissues, we generated
      R26Sall1 mice, in which Rosa26 locus stop sequences flanked by two loxP sites
      were located upstream of the Sall1 cDNA. This allele allowed exogenous Sall1
      expression in a Cre recombinase-dependent manner. R26Sall1 mice were first
      crossed with CAGCre mice, which expressed Cre recombinase ubiquitously during
      embryogenesis. Mice expressing Sall1 ubiquitously were smaller in size compared
      with mice of other genotypes. We then crossed R26Sall1 mice with Six2Cre mice
      expressing Cre recombinase in the metanephric mesenchyme during kidney
      development. However, no kidney defects were observed. Taken together,
      overexpression of Sall1 does not affect kidney development, but does lead to a
      reduced body weight, suggesting that the optimal dosage of Sall1 is required for
      normal mouse development.

PMID- 20053787
TI  - Interferon-alpha induces the growth inhibition of human T-cell leukaemia line
      Jurkat through p38alpha and p38beta.
AB  - Interferon alpha (IFN-alpha) modulates the proliferation of different human
      tumour cell lines. It has been shown that IFN-alpha induces the growth inhibition
      of T-cell acute lymphoblastic leukaemia (T-ALL). However, its intracellular
      signalling mechanisms remain unknown. This study found that IFN-alpha inhibited
      the cell proliferation of human T-ALL cell line Jurkat in a dose- and time
      dependent manner. A p38 inhibitor (SB203580), but not an extracellular signal
      regulated kinase 1/2 inhibitor (PD98059) or c-Jun N-terminal kinase inhibitor
      (SP600125), eliminated IFN-alpha inhibition of Jurkat cell proliferation,
      indicating that p38 pathway is crucial for IFN-alpha-mediated growth inhibition.
      SB203580 targeted two p38 isoforms, p38alpha and p38beta. The expression of
      p38alpha and p38beta mRNA in Jurkat cells was examined by reverse transcriptase
      polymerase chain reaction. The kinase activity of p38alpha and p38beta was
      activated by IFN-alpha in Jurkat cells. To investigate the role of p38alpha and
      p38beta isoforms in IFN-alpha-mediated growth inhibition, we generated stable
      clones that overexpressed the dominant-negative p38 isoform, p38alpha(AF) or
      p38beta(AF), in Jurkat cells. Overexpression of p38alpha(AF) or p38beta(AF)
      inhibited IFN-alpha-mediated p38 kinase activity and growth inhibition in Jurkat
      cells. Similarly, down-regulation of either p38alpha or p38beta by isoform
      specific small interference RNAs also reduced IFN-alpha-mediated growth
      inhibition. These results demonstrate that IFN-alpha can regulate growth
      inhibition of Jurkat cells through p38alpha and p38beta.

PMID- 20053789
TI  - Communication about smoking between depressed adolescents and their parents.
AB  - INTRODUCTION: Better understanding of effective parent-adolescent communication
      regarding tobacco use could inform smoking cessation intervention. METHODS:
      Semistructured interviews related to communication about smoking were conducted
      with 15 depressed adolescent smokers and their parents, primarily from urban
      areas. This study, conducted in 2006-2008, was funded by the Pennsylvania
      Department of Health. Interview transcripts (N = 30) were coded in QSR N6.
      RESULTS: Quality of communication, rather than content, seemed to determine
      whether parental communication was effective. Parents reactivity to, or avoidance
      of, adolescent smoking presented a barrier to effective communication. In this
      sample, parents and adolescents were more concerned about problems, such as
      depression, than smoking. DISCUSSION: Involving parents in adolescent smoking
      cessation programs may be promising. Parental involvement may include teaching
      parent-child communication skills, building stronger relational bonds, or helping
      parents quit simultaneously. Further research is needed to explore whether
      coupling smoking cessation with depression treatment increases parent and
      adolescent treatment engagement and effectiveness.

PMID- 20053788
TI  - A pilot randomized study of smokeless tobacco use among smokers not interested in
      quitting: changes in smoking behavior and readiness to quit.
AB  - INTRODUCTION: Several prior studies suggest that smokeless tobacco use results in
      less carcinogenic risk than does cigarette smoking. Whether smokers will use
      smokeless tobacco is unclear, as is the impact of such use on long-term smoking
      behavior and cessation. It is equally plausible that smokeless tobacco use among
      smokers could either (a) increase total tobacco exposure and undermine motivation
      to quit or (b) decrease overall tobacco exposure, motivate smokers to quit, and
      enhance cessation. Either outcome is of major public health significance.
      METHODS: In this small (N = 31), short-term (2 week) pilot study, smokers
      uninterested in quitting were randomized to (a) receive Ariva or Stonewall (both
      spitless and smokeless tobacco lozenges) or (b) continue smoking conventional
      cigarettes. RESULTS: Ariva/Stonewall use led to a significant reduction (40%, 95%
      CI: 24%-55%) in cigarettes per day, no significant increases in total tobacco use
      (cigarettes + Ariva/Stonewall; p > .05), and significant increases in two
      measures of readiness to quit, either in the next month (p < .001) or within the
      next 6 months (p = .04), as well as significant increases in self-efficacy to
      quit smoking (p < .001). No such changes were found among smokers maintained on
      conventional cigarettes. DISCUSSION: These results suggest no deleterious effect
      on short-term smoking and quitting behavior among smokers who use smokeless
      tobacco. More broadly, this study suggests a strong need for a large prospective
      randomized clinical trial to more accurately assess the long-term viability of
      smokeless tobacco use as a method for cessation induction among unmotivated
      smokers.

PMID- 20053790
TI  - p66SHC-mediated mitochondrial dysfunction in renal proximal tubule cells during
      oxidative injury.
AB  - Mitochondrial dysfunction is involved in pathopysiology of ischemia-reperfusion
      induced acute kidney injury (AKI). The p66shc adaptor protein is a newly
      recognized mediator of mitochondrial dysfunction, which might play a role in AKI
      induced renal tubular injury. Oxidative stress-mediated Serine36 phosphorylation
      of p66shc facilitates its transportation to the mitochondria where it oxidizes
      cytochrome c and generates excessive amount of reactive oxygen species (ROS). The
      consequence is mitochondrial depolarization and injury. Earlier we determined
      that p66shc plays an essential role in injury of cultured mouse renal proximal
      tubule cells during oxidative stress. Here, we studied the role of p66shc in ROS
      generation and consequent mitochondrial dysfunction during oxidative injury in
      renal proximal tubule cells. We employed p66shc knockdown renal proximal tubule
      cells and cells that overexpress wild-type, Serine phosphorylation (S36A), or
      cytochrome c-binding (W134F) mutants of p66shc. Inhibition of the mitochondrial
      electron transport chain or the mitochondrial permeability transition revealed
      that hydrogen peroxide-induced injury is mitochondrial ROS and consequent
      mitochondrial depolarization dependent. We also found that through Ser36
      phosphorylation and mitochondria/cytochrome c binding, p66shc mediates those
      effects. We propose a similar mechanism in vivo as we demonstrated mitochondrial
      binding of p66shc as well as its association with cytochrome c in the
      postischemic kidneys of mice. Thus, manipulating p66shc might offer a new
      therapeutic modality to ameliorate renal ischemic injury.

PMID- 20053791
TI  - CREB trans-activation of disruptor of telomeric silencing-1 mediates forskolin
      inhibition of CTGF transcription in mesangial cells.
AB  - Connective tissue growth factor (CTGF) participates in diverse fibrotic processes
      including glomerulosclerosis. The adenylyl cyclase agonist forskolin inhibits
      CTGF expression in mesangial cells by unclear mechanisms. We recently reported
      that the histone H3K79 methyltransferase disruptor of telomeric silencing-1
      (Dot1) suppresses CTGF gene expression in collecting duct cells (J Clin Invest
      117: 773-783, 2007) and HEK 293 cells (J Biol Chem In press). In the present
      study, we characterized the involvement of Dot1 in mediating the inhibitory
      effect of forskolin on CTGF transcription in mouse mesangial cells.
      Overexpression of Dot1 or treatment with forskolin dramatically suppressed basal
      CTGF mRNA levels and CTGF promoter-luciferase activity, while hypermethylating
      H3K79 in chromatin associated with the CTGF promoter. siRNA knockdown of Dot1
      abrogated the inhibitory effect of forskolin on CTGF mRNA expression. Analysis of
      the Dot1 promoter sequence identified a CREB response element (CRE) at -384/-380.
      Overexpression of CREB enhanced forskolin-stimulated Dot1 promoter activity. A
      constitutively active CREB mutant (CREB-VP16) strongly induced Dot1 promoter
      luciferase activity, whereas overexpression of CREBdLZ-VP16, which lacks the CREB
      DNA-binding domain, abolished this activation. Mutation of the -384/-380 CRE
      resulted in 70% lower levels of Dot1 promoter activity. ChIP assays confirmed
      CREB binding to the Dot1 promoter in chromatin. We conclude that forskolin
      stimulates CREB-mediated trans-activation of the Dot1 gene, which leads to
      hypermethylation of histone H3K79 at the CTGF promoter, and inhibition of CTGF
      transcription. These data are the first to describe regulation of the Dot1 gene,
      and disclose a complex network of genetic and epigenetic controls on CTGF
      transcription.

PMID- 20053792
TI  - Exocyst Sec10 protects epithelial barrier integrity and enhances recovery
      following oxidative stress, by activation of the MAPK pathway.
AB  - Cell-cell contacts are essential for epithelial cell function, and disruption is
      associated with pathological conditions including ischemic kidney injury. We
      hypothesize that the exocyst, a highly-conserved eight-protein complex that
      targets secretory vesicles carrying membrane proteins, is involved in maintaining
      renal epithelial barrier integrity. Accordingly, increasing exocyst expression in
      renal tubule cells may protect barrier function from oxidative stress resulting
      from ischemia and reperfusion (I/R) injury. When cultured on plastic, Madin-Darby
      canine kidney (MDCK) cells overexpressing Sec10, a central exocyst component,
      formed domes showing increased resistance to hydrogen peroxide (H2O2).
      Transepithelial electric resistance (TER) of Sec10-overexpressing MDCK cells
      grown on Transwell filters was higher than in control MDCK cells, and the rate of
      TER decrease following H2O2 treatment was less in Sec10-overexpressing MDCK cells
      compared with control MDCK cells. After removal of H2O2, TER returned to normal
      more rapidly in Sec10-overexpressing compared with control MDCK cells. In
      collagen culture MDCK cells form cysts, and H2O2 treatment damaged Sec10
      overexpressing MDCK cell cysts less than control MDCK cell cysts. The MAPK
      pathway has been shown to protect animals from I/R injury. Levels of active ERK,
      the final MAPK pathway step, were higher in Sec10-overexpressing compared with
      control MDCK cells. U0126 inhibited ERK activation, exacerbated the H2O2-induced
      decrease in TER and cyst disruption, and delayed recovery of TER following H2O2
      removal. Finally, in mice with renal I/R injury, exocyst expression decreased
      early and returned to normal concomitant with functional recovery, suggesting
      that the exocyst may be involved in the recovery following I/R injury.

PMID- 20053793
TI  - cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton
      extrusion in kidney collecting duct A-intercalated cells.
AB  - Kidney proton-secreting A-intercalated cells (A-IC) respond to systemic acidosis
      by accumulating the vacuolar ATPase (V-ATPase) in their apical membrane and by
      increasing the length and number of apical microvilli. We show here that the cell
      permeant cAMP analog CPT-cAMP, infused in vivo, results in an almost twofold
      increase in apical V-ATPase accumulation in AE1-positive A-IC within 15 min and
      that these cells develop an extensive array of apical microvilli compared with
      controls. In contrast, no significant change in V-ATPase distribution could be
      detected by immunocytochemistry in B-intercalated cells at the acute time point
      examined. To show a direct effect of cAMP on A-IC, we prepared cell suspensions
      from the medulla of transgenic mice expressing EGFP in IC (driven by the B1
      subunit promoter of the V-ATPase) and exposed them to cAMP analogs in vitro.
      Three-dimensional reconstructions of confocal images revealed that cAMP induced a
      time-dependent growth of apical microvilli, starting within minutes after
      addition. This effect was blocked by the PKA inhibitor myristoylated PKI. These
      morphological changes were paralleled by increased cAMP-mediated proton extrusion
      (pHi recovery) by A-IC in outer medullary collecting ducts measured using the
      ratiometric probe BCECF. These results, and our prior data showing that the
      bicarbonate-stimulated soluble adenylyl cyclase (sAC) is highly expressed in
      kidney intercalated cells, support the idea that cAMP generated either by sAC, or
      by activation of other signaling pathways, is part of the signal transduction
      mechanism involved in acid-base sensing and V-ATPase membrane trafficking in
      kidney intercalated cells.

PMID- 20053794
TI  - PKC-alpha mediates flow-stimulated superoxide production in thick ascending
      limbs.
AB  - We showed that luminal flow increases net superoxide (O(2)(-)) production via
      NADPH oxidase in thick ascending limbs. Protein kinase C (PKC) activates NADPH
      oxidase activity in phagocytes, cardiomyocytes, aortic endothelial cells,
      vascular smooth muscle cells, and renal mesangial cells. However, the flow
      activated pathway that induces NADPH oxidase activity in thick ascending limbs is
      unclear. We hypothesized that PKC mediates flow-stimulated net O(2)(-) production
      by thick ascending limbs. Initiation of flow (20 nl/min) increased net O(2)(-)
      production from 4 +/- 1 to 61 +/- 12 AU/s (P < 0.007; n = 5). The NADPH oxidase
      inhibitor apocynin completely blocked the flow-induced increase in net O(2)(-)
      production (2 +/- 1 vs. 1 +/- 1 AU/s; P > 0.05; n = 5). Flow-stimulated O(2)(-)
      was also blocked in p47(phox)-deficient mice. We measured flow-stimulated PKC
      activity with a fluorescence resonance energy transfer (FRET)-based membrane
      targeted PKC activity reporter and found that the FRET ratio increased from 0.87
      +/- 0.02 to 0.96 +/- 0.04 AU (P < 0.05; n = 6). In the absence of flow, the PKC
      activator phorbol 12-myristate 13-acetate (200 nM) enhanced net O(2)(-)
      production from 5 +/- 2 to 92 +/- 6 AU/s (P < 0.001; n = 6). The PKC-alpha- and
      betaI-selective inhibitor Go 6976 (100 nM) decreased flow-stimulated net O(2)(-)
      production from 54 +/- 15 to 2 +/- 1 AU/s (P < 0.04; n = 5). Flow-induced net
      O(2)(-) production was inhibited in thick ascending limbs transduced with
      dominant-negative (dn)PKC-alpha but not dnPKCbetaI or LacZ (Delta = 11 +/- 3 AU/s
      for dnPKCalpha, 55 +/- 7 AU/s for dnPKCbetaI, and 63 +/- 7 AU/s for LacZ; P <
      0.001; n = 6). We concluded that flow stimulates net O(2)(-) production in thick
      ascending limbs via PKC-alpha-mediated activation of NADPH oxidase.

PMID- 20053795
TI  - Human multidrug and toxin extrusion 1 (MATE1/SLC47A1) transporter: functional
      characterization, interaction with OCT2 (SLC22A2), and single nucleotide
      polymorphisms.
AB  - Renal elimination of a number of cationic compounds is thought to be mediated by
      the organic cation transporter 2 (OCT2, SLC22A2), a drug uptake transporter
      expressed at the basolateral domain of renal tubular cells. Recently, the key
      efflux transporter for the secretion organic cations was identified as an
      electroneutral H(+)/organic cation exchanger termed the multidrug and toxin
      extrusion (MATE)-type transporter 1 (MATE1, SLC47A1). The key goals of this study
      were to assess the interplay between the renal cationic transporters OCT2 and
      MATE1 and the functional assessment of genetic variation in human MATE1. First,
      the ability of various agents to interact with OCT2- or MATE1-mediated transport
      was determined using a recombinant vaccinia expression system. We were able to
      identify several drugs in clinical use with a divergent inhibitory capacity for
      these transporters. Subsequently, we further assessed the effect of those
      compounds on the cellular accumulation of shared substrates using OCT2 and MATE1
      double-transfected cells. Consistent with data obtained using single transporter
      transfected cells, compounds that exhibited preferential inhibition of MATE1 such
      as rapamycin and mitoxantrone induced significant cellular accumulation of
      cationic substrates. We next assessed the functional relevance of MATE1 genetic
      polymorphisms. Significant loss of transport activity for metformin and
      tetraethylammonium was noted for two nonsynonymous single nucleotide
      polymorphisms (SNPs), c.404T>C (p.159T>M) and c.1012G>A (p.338V>A). The c.404T>C
      was only seen in Asian subjects with an allele frequency of 1%, and the c.1012G>A
      SNP was much more common, especially among those of African descent. In
      conclusion, we show that coordinate function of MATE1 with OCT2 likely
      contributes to the vectorial renal elimination of organic cationic drugs and that
      altered activity of MATE1, whether by drugs or polymorphisms, should be
      considered as an important determinant of renal cationic drug elimination.

PMID- 20053797
TI  - Isoflurane via TGF-beta1 release increases caveolae formation and organizes
      sphingosine kinase signaling in renal proximal tubules.
AB  - We previously showed that the inhalational anesthetic isoflurane protects against
      renal proximal tubule necrosis via isoflurane-mediated stimulation and
      translocation of sphingosine kinase-1 (SK1) with subsequent synthesis of
      sphingosine-1-phosphate (S1P) in renal proximal tubule cells (Kim M, Kim M, Kim
      N, D'Agati VD, Emala CW Sr, Lee HT. Am J Physiol Renal Physiol 293: F1827-F1835,
      2007). We also demonstrated that the anti-necrotic and anti-inflammatory effect
      of isoflurane is due in part to phosphatidylserine (PS) externalization and
      subsequent release of transforming growth factor-beta1 (TGF-beta1) (Lee HT, Kim
      M, Kim J, Kim N, Emala CW. Am J Nephrol 27: 416-424, 2007). In this study, we
      tested the hypothesis that isoflurane, via TGF-beta1 release, increases caveolae
      formation in the buoyant fraction of the cell membrane of human renal proximal
      tubule (HK-2) cells to organize SK1 and S1P signaling. To detect SK1 protein in
      the caveolae/caveolin fractions, we overexpressed human SK1 in HK-2 cells (SK1-HK
      2). SK1-HK-2 cells exposed to isoflurane increased caveolae/caveolin formation in
      the buoyant membrane fractions which contained key signaling intermediates
      involved in isoflurane-mediated renal tubule protection, including S1P, SK1, ERK
      MAPK, and TGF-beta1 receptors. Furthermore, treating SK1-HK-2 cells with
      recombinant TGF-beta1 or PS liposome mixture increased caveolae formation,
      mimicking the effects of isoflurane. Conversely, TGF-beta1-neutralizing antibody
      blocked the increase in caveolae formation induced by isoflurane in SK1-HK-2
      cells. The increase in SK1 activity in the caveolae-enriched fractions from
      isoflurane-treated nonlentivirus-infected HK-2 cells, while smaller in magnitude,
      was qualitatively similar to that found in the SK1-HK-2 cell line. Finally,
      isoflurane also increased caveolae formation in the kidneys of TGF-beta1 +/+ mice
      but not in TGF-beta1 +/- mice (mice with reduced levels of TGF-beta1). Our study
      demonstrates that isoflurane organizes several key cytoprotective signaling
      intermediates including TGF-beta1 receptors, SK1 and ERK, within the caveolae
      fraction of the plasma membrane. Our findings may help to unravel the cellular
      signaling pathways of volatile anesthetic-mediated renal protection and lead to
      new therapeutic applications of inhalational anesthetics during the perioperative
      period.

PMID- 20053798
TI  - CRYPTOCHROME 1 is implicated in promoting R protein-mediated plant resistance to
      Pseudomonas syringae in Arabidopsis.
AB  - Plants have evolved complex mechanisms to defend themselves against pathogens. It
      has been shown that several defense responses are influenced by light, and the
      red/far-red light photoreceptor phytochromes (PHY) modulate plant defense
      responses in Arabidopsis. Blue light receptor cryptochromes (CRY) work together
      with PHY to regulate many light-controlled responses, including
      photomorphogenesis, floral induction, and entrainment of the circadian clock. We
      report here that the Arabidopsis blue light photoreceptor CRY1 positively
      regulates inducible resistance to Pseudomonas syringae under continuous light
      conditions. By challenging plants with P. syringae pv. tomato (Pst.) DC3000
      carrying avrRpt2, we demonstrate that effector-triggered local resistance is down
      regulated in the cry1 mutant, leading to more pathogen multiplication. In plants
      overexpressing CRY1 (CRY1-ovx), however, local resistance is significantly up
      regulated. We also show that systemic acquired resistance (SAR) is positively
      regulated by CRY1, and that salicylic acid (SA)-induced pathogenesis-related gene
      PR-1 expression is reduced in the cry1 mutant, but enhanced in CRY1-ovx plants.
      However, our results indicate that CRY1 only modestly influences SA accumulation
      and has no effect on hypersensitive cell death. These results suggest that CRY1
      may positively regulate R protein-mediated resistance to P. syringae with
      increased PR gene expression.

PMID- 20053796
TI  - Functional implications of the three-dimensional architecture of the rat renal
      inner medulla.
AB  - A new, region-based mathematical model of the urine concentrating mechanism of
      the rat renal inner medulla (IM) was used to investigate the significance of
      transport and structural properties revealed in recent studies that employed
      immunohistochemical methods combined with three-dimensional computerized
      reconstruction. The model simulates preferential interactions among tubules and
      vessels by representing two concentric regions. The inner region, which
      represents a collecting duct (CD) cluster, contains CDs, some ascending thin
      limbs (ATLs), and some ascending vasa recta; the outer region, which represents
      the intercluster region, contains descending thin limbs, descending vasa recta,
      remaining ATLs, and additional ascending vasa recta. In the upper portion of the
      IM, the model predicts that interstitial Na(+) and urea concentrations (and
      osmolality) in the CD clusters differ significantly from those in the
      intercluster regions: model calculations predict that those CD clusters have
      higher urea concentrations than the intercluster regions, a finding that is
      consistent with a concentrating mechanism that depends principally on the mixing
      of NaCl from ATLs and urea from CDs. In the lower IM, the model predicts that
      limited or nearly zero water permeability in descending thin limb segments will
      increase concentrating effectiveness by increasing the rate of solute-free water
      absorption. The model predicts that high urea permeabilities in the upper
      portions of ATLs and increased contact areas of longest loop bends with CDs both
      modestly increase concentrating capability. A surprising finding is that the
      concentrating capability of this region-based model falls short of the capability
      of a model IM that has radially homogeneous interstitial fluid at each level but
      is otherwise analogous to the region-based model.

PMID- 20053799
TI  - Roles of Arabidopsis patatin-related phospholipases a in root development are
      related to auxin responses and phosphate deficiency.
AB  - Phospholipase A enzymes cleave phospho- and galactolipids to generate free fatty
      acids and lysolipids that function in animal and plant hormone signaling. Here,
      we describe three Arabidopsis patatin-related phospholipase A (pPLA) genes
      AtPLAIVA, AtPLAIVB, and AtPLAIVC and their corresponding proteins. Loss-of
      function mutants reveal roles for these pPLAs in roots during normal development
      and under phosphate deprivation. AtPLAIVA is expressed strongly and exclusively
      in roots and AtplaIVA-null mutants have reduced lateral root development,
      characteristic of an impaired auxin response. By contrast, AtPLAIVB is expressed
      weakly in roots, cotyledons, and leaves but is transcriptionally induced by
      auxin, although AtplaIVB mutants develop normally. AtPLAIVC is expressed in the
      floral gynaecium and is induced by abscisic acid (ABA) or phosphate deficiency in
      roots. While an AtplaIVC-1 loss-of-function mutant displays ABA responsiveness,
      it exhibits an impaired response to phosphate deficiency during root development.
      Recombinant AtPLA proteins hydrolyze preferentially galactolipids and, less
      efficiently, phospholipids, although these enzymes are not localized in
      chloroplasts. We find that AtPLAIVA and AtPLAIVB are phosphorylated by calcium
      dependent protein kinases in vitro and this enhances their activities on
      phosphatidylcholine but not on phosphatidylglycerol. Taken together, the data
      reveal novel functions of pPLAs in root development with individual roles at the
      interface between phosphate deficiency and auxin signaling.

PMID- 20053800
TI  - Aneurysmal changes at the basilar terminus in the rabbit elastase aneurysm model.

PMID- 20053801
TI  - Percutaneous vertebroplasty and procedural pain.
AB  - BACKGROUND AND PURPOSE: No consensus exists regarding pain management during PV.
      In this study, we evaluated the effectiveness of local infiltration anesthesia as
      the only pain medication. MATERIALS AND METHODS: From September 2008 to March
      2009, 44 consecutive patients (35 women and 9 men; mean age, 74 years) with
      symptomatic OVCFs were included in the study. Lidocaine was infiltrated to the
      skin and the periosteum of the pedicle. After PV, patients indicated pain
      sensation on a VAS. In addition, patients indicated the most painful moment
      during the procedure: lidocaine infiltration, placing the needles, or cement
      injection. Finally, patients were asked whether pain medication during the
      procedure was sufficient. After the procedure the surgeon was asked to judge the
      expected VAS score of the patient. RESULTS: Mean VAS score was 5.7 (median, 6;
      range, 1-10). Seventeen of 44 patients (39%) indicated that lidocaine
      infiltration was insufficient for procedural pain reduction. The mean VAS score
      of these patients was 7.3 (range, 5-10). Placing the needles was specified as
      most painful moment in 29 patients (66%), lidocaine infiltration in 11 (25%), and
      cement injection in 4 (9%). Surgeons' expectations of patients' VAS scores were a
      mean of 3.3 (median, 3; range, 1-6). CONCLUSIONS: For a substantial proportion of
      patients, local infiltration anesthesia was not sufficient for pain reduction
      during PV. The severity of pain experienced by the patient is usually not
      appreciated correctly by the surgeon.

PMID- 20053802
TI  - Abrupt regression of a meningioma after discontinuation of cyproterone treatment.
AB  - The multiplicity of meningiomas or abrupt lesion growth in patients treated with
      cyproterone acetate suggests that this progestative treatment may promote lesion
      growth. We report the rapid regression of an incidental meningioma after
      discontinuation of a 10-year cyproterone acetate treatment. This unique
      observation suggests that conservative management of meningiomas may be the best
      option among users of high doses of cyproterone acetate, given that spontaneous
      regression may occur after hormonal treatment discontinuation.

PMID- 20053803
TI  - Hippocampal abnormalities in an MR imaging series of patients with tuberous
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Hippocampal abnormalities are known as highly
      epileptogenic precursor lesions in the general population, primarily manifesting
      as MTS. The purpose of this study was to evaluate the occurrence of hippocampal
      abnormalities on MR imaging in patients with TS to explore the possible
      underlying mechanisms of the abnormalities and to identify the relationship
      between an abnormal HF and epilepsy. MATERIALS AND METHODS: We studied MR images
      and clinical data from 31 patients with TS. The MR imaging protocol was identical
      for all patients and included tilted coronal images of their temporal lobes. The
      diagnosis of TSC was made according to established criteria. The HFs of the
      patients were evaluated from coronal images according to size, morphology, and
      signal intensity. The data were submitted to statistical analysis, and P values <
      or = .05 were considered significant. RESULTS: We found HF abnormalities in 5
      patients. Four had typical MTS, and 1 had HIMAL. We found a positive correlation
      between childhood febrile seizures and MTS in patients with TS. We also confirmed
      that patients with altered hippocampi had a tendency to exhibit more cortical
      tubers. CONCLUSIONS: Analysis of this series of patients demonstrated the
      presence of HF abnormalities, mainly MTS in patients with TS. We also found that
      the occurrence of febrile seizures during the first year of life appears to be
      one of the determining factors for MTS development in these patients.

PMID- 20053804
TI  - The changing trends of modern teaching.

PMID- 20053805
TI  - Percutaneous treatment of cervical disk hernias using gelified ethanol.
AB  - This study investigates the efficacy of chemonucleolysis using RGE in the
      treatment of cervical disk hernias in a small sample of patients who had cervical
      diskogenic or radicular pain secondary to disk herniations. Results were
      satisfactory in 89.5% patients, with no adverse events recorded during the
      procedure or after. The use of RGE shows promising results and might be a
      feasible and safe alternative in the treatment of cervical disk hernias.

PMID- 20053806
TI  - Attenuation of cerebral venous contrast in susceptibility-weighted imaging of
      spontaneously breathing pediatric patients sedated with propofol.
AB  - BACKGROUND AND PURPOSE: SWI is known for its detailed visualization of the
      cerebral venous system and seems to be a promising tool for early detection of
      cerebrovascular pathologies in children, who are frequently sedated for MR
      imaging. Because sedation influences cerebral hemodynamics, we hypothesized that
      it would affect cerebral venous contrast in SWI. MATERIALS AND METHODS: SWI (125
      examinations) of 26 patients (age, 2-16 years) was reviewed in this study. Images
      were acquired of patients sedated with propofol. Reviewers classified the images
      by weak or strong venous contrast. Physiologic data, such as etCO(2), BP, age,
      and CBF by arterial spin-labeling, were monitored and collected during MR
      imaging. A generalized estimating equation approach was used to model
      associations of these parameters with venous contrast. RESULTS: EtCO(2) and CBF
      were found to correlate with venous contrast, suggesting that patients with high
      etCO(2) and CBF have weak contrast and patients with low etCO(2) and CBF have
      strong contrast. BP was also found to correlate with the venous contrast of SWI,
      suggesting that patients with high BP have strong venous contrast. No significant
      correlations were found for any other physiologic parameters. CONCLUSIONS: We
      found that the venous contrast in SWI is affected by propofol sedation in
      spontaneously breathing patients. We also found that low etCO(2), low CBF, and
      high BP are associated with strong venous contrast. Reviewing SWI data in light
      of physiologic measures may therefore help prevent potential misinterpretations
      of weak venous contrast in SWI examinations under propofol sedation.

PMID- 20053807
TI  - Selective brain cooling with endovascular intracarotid infusion of cold saline: a
      pilot feasibility study.
AB  - BACKGROUND AND PURPOSE: Endovascular brain cooling as a method for rapid and
      selective induction of hypothermic neuroprotection has not been systematically
      studied in humans. In this clinical pilot study we investigated the feasibility,
      safety, and physiologic responses of short-term brain cooling with IC-CSI.
      MATERIALS AND METHODS: We studied 18 patients (50 +/- 10 years old, 9 women)
      undergoing follow-up cerebral angiography after previous treatment of vascular
      malformations. Isotonic saline (4-17 degrees C) was infused into 1 internal
      carotid artery at 33 mL/min for 10 minutes. Brain (JVB) and bladder/esophageal
      temperature measurements (n = 9) were performed. Both MCAs were monitored with
      transcranial Doppler sonography (n = 13). Arterial and JV blood were sampled to
      estimate hemodilution and brain oxygen extraction. RESULTS: JVB temperature
      dropped approximately 0.84 +/- 0.13 degrees C and systemic temperature by 0.15 +/
      0.08 degrees C from baseline (JVB versus systemic temperature: P = .0006).
      Systolic MCA-flow velocities decreased from 101 +/- 27 to 73 +/- 18 cm/s on the
      infused side and from 83 +/- 24 to 78 +/- 21 cm/s on the contralateral side
      (relative changes, -26 +/- 8% versus -4 +/- 27%; P = .009). Changes in hematocrit
      (-1.2 +/- 1.1%) and cerebral arteriovenous oxygen difference (0.2 +/- 1.0 mL
      O(2)/100 mL) were not significant. Doppler data showed no signs of vascular spasm
      or microemboli. No focal neurologic deficits occurred. Pain was not reported.
      CONCLUSIONS: The results of this pilot study suggest that brain cooling can be
      achieved safely, rapidly, and selectively by means of IC-CSI, opening a new
      potential avenue for acute neuroprotection. Clinical investigations with control
      of infusion parameters and measurements of CBF, oxygen consumption, and brain
      temperature are warranted.

PMID- 20053808
TI  - Adult lumbar scoliosis: underreported on lumbar MR scans.
AB  - BACKGROUND AND PURPOSE: Adult lumbar scoliosis is an increasingly recognized
      entity that may contribute to back pain. We investigated the epidemiology of
      lumbar scoliosis and the rate at which it is unreported on lumbar MR images.
      MATERIALS AND METHODS: The coronal and sagittal sequences of lumbar spine MR
      imaging scans of 1299 adult patients, seeking care for low back pain, were
      reviewed to assess for and measure the degree of scoliosis and spondylolisthesis.
      Findings were compared with previously transcribed reports by subspecialty
      trained neuroradiologists. Inter- and intraobserver reliability was calculated.
      RESULTS: The prevalence of adult lumbar scoliosis on MR imaging was 19.9%, with
      higher rates in ages >60 years (38.9%, P < .001) and in females (22.6%, P =
      .002). Of scoliotic cases, 66.9% went unreported, particularly when the scoliotic
      angle was <20 degrees (73.9%, P < .001); 10.5% of moderate to severe cases were
      not reported. Spondylolisthesis was present in 15.3% (199/1299) of cases,
      demonstrating increased rates in scoliotic patients (32.4%, P < .001), and it was
      reported in 99.5% of cases. CONCLUSIONS: Adult lumbar scoliosis is a prevalent
      condition with particularly higher rates among older individuals and females but
      is underreported on spine MR images. This can possibly result in delayed 1)
      identification of a potential cause of low back pain, 2) referral to specialized
      professionals for targeted evaluation and management, and 3) provision of health
      care. The coronal "scout images" should be reviewed as part of the complete
      lumbar spine evaluation if dedicated coronal sequences are not already part of
      the spine protocol.

PMID- 20053809
TI  - C-arm CT measurement of cerebral blood volume in ischemic stroke: an experimental
      study in canines.
AB  - BACKGROUND AND PURPOSE: CBV is a key parameter in distinguishing penumbra from
      ischemic core. The purpose of this study was to compare CBV measurements acquired
      with standard PCT with ones obtained with C-arm CT in a canine stroke model.
      MATERIALS AND METHODS: Under an institutionally approved protocol, unilateral MCA
      strokes were created in 10 canines. Four hours later, DWI was used to confirm the
      presence of an infarct. CBV maps acquired with PCT were compared with ones
      acquired by using C-arm CT. Three experienced observers, blinded to the technique
      used for acquisition, evaluated the CBV maps. RESULTS: An ischemic stroke was
      achieved in 9 of the 10 animals. Areas of reduced CBV were detected in 70%-75% of
      the PCT studies and in 83%-87% of the C-arm CT examinations, with false-positives
      in 1.7% and 3.3%, respectively. False-negatives were found in 25% of the PCT and
      12.2% of the C-arm CT studies. In all studies, there was a significant difference
      between the absolute CBV values in normal and abnormal tissue (P < .005) and no
      significant difference between PCT and C-arm CT CBV values in either the normal
      or the abnormal parenchyma (P > .05). CONCLUSIONS: CBV measurements made with C
      arm CT compare well with ones made with PCT. While further work is required both
      to fully validate the technique and to define its ultimate clinical value, it
      appears that it offers a feasible method for assessing CBV in the angiography
      suite.

PMID- 20053810
TI  - Simultaneous bilateral carotid stenting in high-risk patients.
AB  - BACKGROUND AND PURPOSE: The safety and efficacy of SBCAS have not been evaluated
      in detail. The purpose of our study was to evaluate the outcome after SBCAS in
      high-risk patients compared with unilateral stent placement. MATERIALS AND
      METHODS: Between March 2002 and October 2008, a total of 205 consecutive high
      risk patients underwent CAS at our institution. Of these patients, 30 (14.6%)
      underwent SBCAS (n = 24) and staged SBCAS (n = 6). Patients who underwent
      unilateral CAS (n = 175) during the same period served as controls. The stroke
      risk factors, procedural results, and outcome at 30 days and 6 months, as well as
      the restenosis rate at 6 months, were compared by using either the chi(2) test or
      the Kruskal-Wallis equality-of-populations rank test. RESULTS: Our data revealed
      no significant differences in the stroke risk factors between the SBCAS and the
      control group. HPS occurred more commonly in SBCAS (ie, 16.7%, 4/24) compared
      with 2.9% (5/175) in the control group (P = .014). However, there was no
      statistical significance between 2 groups in the event rate of stroke (minor
      and/or major stroke), death, or restenosis at 6 months. CONCLUSIONS: There was no
      significant difference in outcome at 6 months following stent placement between
      SBCAS and unilateral CAS in the high-risk patient group, even though HPS occurred
      more commonly after SBCAS.

PMID- 20053811
TI  - Comparison of gadobenate dimeglumine and gadodiamide in the evaluation of spinal
      vascular anatomy with MR angiography.
AB  - BACKGROUND AND PURPOSE: Spinal MRA has been increasingly used to evaluate non
      invasively the spinal cord vasculature. Our aim was to prospectively compare
      gadobenate dimeglumine with gadodiamide in the assessment of the normal spinal
      cord vasculature by using contrast-enhanced MRA, with the hypothesis that high T1
      relaxivity gadolinium compounds may improve visualization of the intradural
      vessels. MATERIALS AND METHODS: Twenty subjects underwent 2 temporally separated
      contrast-enhanced spinal MRAs with gadobenate dimeglumine and gadodiamide (0.2
      mmol/kg). Two blinded observers rated postprocessed images on the following
      qualitative parameters: background homogeneity, sharpness, vascular continuity,
      and contrast enhancement. Delineation of the ASA, AKA, hairpin configuration of
      the ASA-AKA connection, and visualized ASA length were recorded. Each observer
      indicated which of the 2 matched studies he or she thought was of the best
      overall diagnostic quality. RESULTS: According to both observers gadobenate
      dimeglumine was superior to gadodiamide in the representation of vascular
      continuity and contrast (P value < .05). Background homogeneity was not
      significantly different between the studies. One observer favored gadobenate
      dimeglumine over gadodiamide in the demonstration of vascular sharpness, while
      the second observer did not find any significant difference between contrast
      agents. There was no significant difference between contrast agents in the
      visualization of the ASA, AKA, hairpin-shaped ASA-AKA connection, and visualized
      length of the ASA. The overall quality of the gadobenate dimeglumine-enhanced MRA
      was deemed superior in 15 and 16 cases, respectively, by the 2 observers.
      CONCLUSIONS: Improved image quality and vascular contrast enhancement of spinal
      MRA at 1.5T is achieved with high T1 relaxivity gadolinium contrast agents
      compared with conventional agents at equivalent doses.

PMID- 20053812
TI  - Assessment of intracranial arterial stenosis with multidetector row CT
      angiography: a postprocessing techniques comparison.
AB  - BACKGROUND AND PURPOSE: It was demonstrated the some patients with stroke have
      intracranial stenosis of 50% or greater and the identification of intracranial
      arterial stenosis is extremely important in order to plan a correct therapeutical
      approach. The aim of this study was to assess the image quality and
      intertechnique agreement of various postprocessing methods in the detection of
      intracranial arterial stenosis. MATERIAL AND METHODS: Eighty-five patients who
      were studied by using a multidetector row CT scanner were retrospectively
      analyzed. A total of 2040 segments were examined in the 85 subjects. Intracranial
      vasculature was assessed by using MPR, CPR, MIP, and VR techniques. Two
      radiologists reviewed the CT images independently. Cohen weighted kappa statistic
      was applied to calculate interobserver agreement and for image accuracy for each
      reconstruction method. Sensitivity, specificity, PPV, and NPV were also
      calculated by using the consensus read as the reference. RESULTS: Two hundred
      fifteen (10.5%) stenosed artery segments were identified by the observers in
      consensus. The best intermethod kappa values between observers 1 and 2 were
      obtained by VR and MIP (kappa values of 0.878 and 0.861, respectively), whereas
      MPR provided the lowest value (kappa value of 0.282). VR showed a sensitivity for
      detecting stenosed segments of 88.8% and 91.6% for observers 1 and 2,
      respectively. The highest positive predictive value was also obtained by VR at
      95% and 99% for observers 1 and 2, respectively. Image accuracy obtained by using
      VR was the highest among all reconstruction methods in both observers (185/255
      and 177/255 for observers 1 and 2, respectively). CONCLUSIONS: The results of our
      study suggest that VR and MIP techniques provide the best interobserver and
      intertechnique concordance in the analysis of intravascular cranial stenosis.

PMID- 20053813
TI  - A combined immunoprecipitation, mass spectrometric and nucleic acid sequencing
      approach to determine microRNA-mediated post-transcriptional gene regulatory
      networks.
AB  - While initiation of transcription has attracted the most attention in the field
      of gene regulation, it has become clear that additional stages in the gene
      expression cascade including post-transcriptional events are under equally
      exquisite control. The seminal discovery that short RNAs (microRNA, small
      interfering RNA, Piwi-interacting RNA), play important roles in repressing gene
      expression has spurred a rush of new interest in post-transcriptional gene
      silencing mechanisms. The development of affinity tags and high-resolution tandem
      mass spectrometry (MS/MS) has greatly simplified the analysis of proteins that
      regulate gene expression. Further, the use of DNA microarrays and 'second
      generation' nucleic acid sequencing ('deep sequencing') technologies has
      facilitated the identification of their regulatory targets. These technological
      advancements mark a significant step towards a comprehensive understanding of
      gene regulatory networks. The purpose of this review is to highlight several
      recent reports that illustrate the value of affinity-purification
      (immunoprecipitation) followed by mass spectrometric protein analysis and nucleic
      acid analysis by deep sequencing (AP-MS/Seq) to examine mRNA after it has been
      transcribed. The ability to identify the direct nucleic acid targets of post
      transcriptional gene regulatory machines is a critical first step towards
      understanding the contribution of post-transcriptional pathways on gene
      expression.

PMID- 20053815
TI  - Using association mapping to dissect the genetic basis of complex traits in
      plants.
AB  - Association or linkage disequilibrium mapping has become a very popular method
      for dissecting the genetic basis of complex traits in plants. The benefits of
      association mapping, compared with traditional quantitative trait locus mapping,
      is, for example, a relatively detailed mapping resolution and that it is far less
      time consuming since no mapping populations need to be generated. The surge of
      interest in association mapping has been fueled by recent developments in
      genomics that allows for rapid identification and scoring of genetic markers
      which has traditionally limited mapping experiments. With the decreasing cost of
      genotyping future emphasis will likely focus on phenotyping, which can be both
      costly and time consuming but which is crucial for obtaining reliable results in
      association mapping studies. In addition, association mapping studies are prone
      to the identification of false positives, especially if the experimental design
      is not rigorously controlled. For example, population structure has long been
      known to induce many false positives and accounting for population structure has
      become one of the main issues when implementing association mapping in plants.
      Also, with increasing numbers of genetic markers used, the problem becomes
      separating true from false positive and this highlights the need for independent
      validation of identified association. With these caveats in mind, association
      mapping nevertheless shows great promise for helping us understand the genetic
      basis of complex traits of both economic and ecological importance.

PMID- 20053814
TI  - RNAi screens to identify components of gene networks that modulate aging in
      Caenorhabditis elegans.
AB  - Our understanding of the genetic mechanisms of organismal aging has advanced
      dramatically during the past two decades. With the development of large-scale
      RNAi screens, the last few years saw the remarkable identifications of hundreds
      of new longevity genes in the roundworm Caenorhabditis elegans. The various RNAi
      screens revealed many biological pathways previously unknown to be related to
      aging. In this review, we focus on findings from the recent large-scale RNAi
      longevity screens, and discuss insights they have provided into the complex
      biological process of aging and considerations of the RNAi technology will
      continue to have on the future development of the aging field.

PMID- 20053816
TI  - RNAi for functional genomics in plants.
AB  - RNAi refers to several different types of gene silencing mediated by small, dsRNA
      molecules. Over the course of 20 years, the scientific understanding of RNAi has
      developed from the initial observation of unexpected expression patterns to a
      sophisticated understanding of a multi-faceted, evolutionarily conserved network
      of mechanisms that regulate gene expression in many organisms. It has also been
      developed as a genetic tool that can be exploited in a wide range of species.
      Because transgene-induced RNAi has been effective at silencing one or more genes
      in a wide range of plants, this technology also bears potential as a powerful
      functional genomics tool across the plant kingdom. Transgene-induced RNAi has
      indeed been shown to be an effective mechanism for silencing many genes in many
      organisms, but the results from multiple projects which attempted to exploit RNAi
      on a genome-wide scale suggest that there is a great deal of variation in the
      silencing efficacy between transgenic events, silencing targets and silencing
      induced phenotype. The results from these projects indicate several important
      variables that should be considered in experimental design prior to the
      initiation of functional genomics efforts based on RNAi silencing. In recent
      years, alternative strategies have been developed for targeted gene silencing,
      and a combination of approaches may also enhance the use of targeted gene
      silencing for functional genomics.

PMID- 20053817
TI  - Metabolism of intravenous methylnaltrexone in mice, rats, dogs, and humans.
AB  - Methylnaltrexone (MNTX), a selective mu-opioid receptor antagonist, functions as
      a peripherally acting receptor antagonist in tissues of the gastrointestinal
      tract. This report describes the metabolic fate of [(3)H]MNTX or [(14)C]MNTX
      bromide in mice, rats, dogs, and humans after intravenous administration.
      Separation and identification of plasma and urinary MNTX metabolites was achieved
      by high-performance liquid chromatography-radioactivity detection and liquid
      chromatography/mass spectrometry. The structures of the most abundant human
      metabolites were confirmed by chemical synthesis and NMR spectroscopic analysis.
      Analysis of radioactivity in plasma and urine showed that MNTX underwent two
      major pathways of metabolism in humans: sulfation of the phenolic group to MNTX-3
      sulfate (M2) and reduction of the carbonyl group to two epimeric alcohols, methyl
      6alpha-naltrexol (M4) and methyl-6beta-naltrexol (M5). Neither naltrexone nor its
      metabolite 6beta-naltrexol were detected in human plasma after administration of
      MNTX, confirming an earlier observation that N-demethylation was not a metabolic
      pathway of MNTX in humans. The urinary metabolite profiles in humans were
      consistent with plasma profiles. In mice, the circulating and urinary metabolites
      included M5, MNTX-3-glucuronide (M9), 2-hydroxy-3-O-methyl MNTX (M6), and its
      glucuronide (M10). M2, M5, M6, and M9 were observed in rats. Dogs produced only
      one metabolite, M9. In conclusion, MNTX was not extensively metabolized in
      humans. Conversion to methyl-6-naltrexol isomers (M4 and M5) and M2 were the
      primary pathways of metabolism in humans. MNTX was metabolized to a higher extent
      in mice than in rats, dogs, and humans. Glucuronidation was a major metabolic
      pathway in mice, rats, and dogs, but not in humans. Overall, the data suggested
      species differences in the metabolism of MNTX.

PMID- 20053818
TI  - Disposition of [1'-(14)C]stavudine after oral administration to humans.
AB  - The disposition of stavudine, a potent and orally active nucleoside reverse
      transcriptase inhibitor, was investigated in six healthy human subjects. Before
      dosing humans with [1'-(14)C]stavudine, a tissue distribution study was performed
      in Long-Evans rats. Results from this study showed no accumulation of
      radioactivity in any of the tissues studied, indicating that the position of the
      (14)C-label on the molecule was appropriate for the human study. After a single
      80-mg (100 microCi) oral dose of [1'-(14)C]stavudine, approximately 95% of the
      radioactive dose was excreted in urine with an elimination half-life of 2.35 h.
      Fecal excretion was limited, accounting for only 3% of the dose. Unchanged
      stavudine was the major drug-related component in plasma (61% of area under the
      plasma concentration-time curve from time zero extrapolated to infinite time of
      the total plasma radioactivity) and urine (67% of dose). The remaining
      radioactivity was associated with minor metabolites, including mono- and bis
      oxidized stavudine, glucuronide conjugates of stavudine and its oxidized
      metabolite, and an N-acetylcysteine (NAC) conjugate of the ribose (M4) after
      glycosidic cleavage. Formation of metabolite M4 was shown in human liver
      microsomes incubated with 2',3'-didehydrodideoxyribose, the sugar base of
      stavudine, in the presence of NAC. In addition, after similar microsomal
      incubations fortified with GSH, two GSH conjugates, 3'-GS-deoxyribose and 1'-keto
      2',3'-dideoxy-3'-GS-ribose, were observed. This suggests that 2',3'
      didehydrodideoxyribose underwent cytochrome P450-mediated oxidation leading to an
      epoxide intermediate, 2',3'-ribose epoxide, followed by GSH addition. In
      conclusion, absorption and elimination of stavudine were rapid and complete after
      oral dosing, with urinary excretion of unchanged drug as the predominant route of
      elimination in humans.

PMID- 20053819
TI  - Pseudorabies virus US3-mediated inhibition of apoptosis does not affect
      infectious virus production.
AB  - Preventing apoptosis during the early stages of infection of a host cell is
      generally thought to result in a higher yield of progeny virus. The US3 protein
      kinase of pseudorabies virus (PRV) and herpes simplex virus (HSV) is able to
      protect infected cells from apoptosis, which may be one of the reasons why both
      US3null PRV and US3null HSV replicate to lower virus titres in several cell
      types. However, such potential correlation between the higher amount of apoptosis
      in US3null virus-infected cells and the lower virus titres of US3null virus has
      not been investigated directly. In the current study, we found that a broad
      spectrum caspase-inhibitor efficiently inhibited apoptosis in swine testicle and
      human laryngeal epidermoid carcinoma cells infected with US3null or wild-type
      (WT) PRV. However, inhibition of apoptosis did not affect US3null or WT PRV
      extracellular or cell-associated virus titres, nor did it restore the small
      plaque phenotype of US3null PRV.

PMID- 20053820
TI  - Genotype 1 and global hepatitis C T-cell vaccines designed to optimize coverage
      of genetic diversity.
AB  - Immunological control of hepatitis C virus (HCV) is possible and is probably
      mediated by host T-cell responses, but the genetic diversity of the virus poses a
      major challenge to vaccine development. We considered monovalent and polyvalent
      candidates for an HCV vaccine, including natural, consensus and synthetic
      'mosaic' sequence cocktails. Mosaic vaccine reagents were designed using a
      computational approach first applied to and demonstrated experimentally for human
      immunodeficiency virus type 1 (HIV-Delta). Mosaic proteins resemble natural
      proteins, but are assembled from fragments of natural sequences via a genetic
      algorithm and optimized to maximize the coverage of potential T-cell epitopes
      (all 9-mers) found in natural sequences and to minimize the inclusion of rare 9
      mers to avoid vaccine-specific responses. Genotype 1-specific and global vaccine
      cocktails were evaluated. Among vaccine candidates considered, polyvalent mosaic
      sequences provided the best coverage of both known and potential epitopes and had
      the fewest rare epitopes. A global vaccine based on conserved proteins across
      genotypes may be feasible, as a five-antigen mosaic cocktail provided 90, 77 and
      70% coverage of the Core, NS3 and NS4 proteins, respectively; protein coverage
      diminished with increased protein variability, dropping to 38% for NS2. For the
      genotype 1-specific vaccine, the H77 prototype vaccine sequence matched only 50%
      of the potential epitopes in the population, whilst a polyprotein three-antigen
      mosaic cocktail increased potential epitope coverage to 83%. More than 75%
      coverage of all HCV proteins was achieved with a three-antigen mosaic cocktail,
      suggesting that genotype-specific vaccines could also include the more variable
      proteins.

PMID- 20053821
TI  - Nuclear assortment of eIF4E coincides with shut-off of host protein synthesis
      upon poliovirus infection.
AB  - Eukaryotic initiation factor (eIF) 4E is a subunit of the cap-binding protein
      complex, eIF4F, which recognizes the cap structure of cellular mRNAs to
      facilitate translation initiation. eIF4E is assembled into the eIF4F complex via
      its interaction with eIF4G, an event that is under Akt/mTOR regulation. The eIF4E
      eIF4G interaction is regulated by the eIF4E binding partners, eIF4E-binding
      proteins and eIF4E-transporter. Cleavage of eIF4G occurs upon poliovirus
      infection and is responsible for the shut-off of host-cell protein synthesis
      observed early in infection. Here, we document that relocalization of eIF4E to
      the nucleus occurs concomitantly with cleavage of eIF4G upon poliovirus
      infection. This event is not dependent upon virus replication, but is dependent
      on eIF4G cleavage. We postulate that eIF4E nuclear relocalization may contribute
      to the shut-off of host protein synthesis that is a hallmark of poliovirus
      infection by perturbing the circular status of actively translating mRNAs.

PMID- 20053822
TI  - Emergence of monoclonal antibody b12-resistant human immunodeficiency virus type
      1 variants during natural infection in the absence of humoral or cellular immune
      pressure.
AB  - Human immunodeficiency virus type 1 (HIV-1) resistance to broadly neutralizing
      antibodies such as b12, which targets the highly conserved CD4-binding site,
      raises a significant hurdle for the development of a neutralizing antibody-based
      vaccine. Here, 15 individuals were studied of whom seven developed b12-resistant
      viruses late in infection. The study investigated whether immune pressure may be
      involved in the selection of these viruses in vivo. Although four out of seven
      patients showed HIV-1-specific broadly neutralizing activity in serum, none of
      these patients had CD4-binding site-directed antibodies, indicating that strong
      humoral immunity is not a prerequisite for the outgrowth of b12-resistant
      viruses. In virus variants from one patient, who showed extremely weak
      heterologous and autologous neutralizing activity in serum, mutations were
      identified in the envelope that coincided with changes in b12 neutralization
      sensitivity. Lack of cytotoxic T-cell activity against epitopes with and without
      these mutations excluded a role for host cellular immunity in the selection of
      b12-resistant mutant viruses in this patient. However, b12 resistance correlated
      well with increased virus replication kinetics, indicating that selection for
      enhanced infectivity, possibly driven by the low availability of target cells in
      the later stages of disease, may coincide with increased resistance to CD4
      binding site-directed agents, such as b12. These results showed that b12
      resistant HIV-1 variants can emerge during the course of natural infection in the
      absence of both humoral and cellular immune pressure, suggestive of other
      mechanisms playing a role in the selective outgrowth of b12-resistant viruses.

PMID- 20053823
TI  - Stable recombinants of bovine viral diarrhea virus containing a hepatitis C virus
      insert.
AB  - Here we report on a segment in the genomic 3' non-translated region (3'NTR) of
      bovine viral diarrhea virus (BVDV) that is accessible for the insertion of
      foreign sequence elements such as the 5'NTR of hepatitis C virus. Recombinant
      viruses exhibited replication kinetics similar to those of the parental strain,
      and characterization of RNA species after several passages revealed that foreign
      inserts had the same genetic stability as the BVDV 3'NTR. The generation of such
      BVDV recombinants is relevant for several applications.

PMID- 20053824
TI  - RNA-dependent RNA polymerase of hepatitis C virus binds to its coding region RNA
      stem-loop structure, 5BSL3.2, and its negative strand.
AB  - The hepatitis C virus NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme
      involved in viral replication. Interaction between NS5B RdRp and the viral RNA
      sequence is likely to be an important step in viral RNA replication. The C
      terminal half of the NS5B-coding sequence, which contains the important cis
      acting replication element, has been identified as an NS5B-binding sequence. In
      the present study, we confirm the specific binding of NS5B to one of the RNA stem
      loop structures in the region, 5BSL3.2. In addition, we show that NS5B binds to
      the complementary strand of 5BSL3.2 (5BSL3.2N). The bulge structure of 5BSL3.2N
      was shown to be indispensable for tight binding to NS5B. In vitro RdRp activity
      was inhibited by 5BSL3.2N, indicating the importance of the RNA element in the
      polymerization by RdRp. These results suggest the involvement of the RNA stem
      loop structure of the negative strand in the replication process.

PMID- 20053825
TI  - Pulmonary infection of mice with human metapneumovirus induces local cytotoxic T
      cell and immunoregulatory cytokine responses similar to those seen with human
      respiratory syncytial virus.
AB  - Human metapneumovirus (hMPV) is a major cause of upper and lower respiratory
      tract infection in infants, the elderly and immunocompromised individuals. Virus
      directed cellular immunity elicited by hMPV infection is poorly understood, in
      contrast to the phylogenetically and clinically related pathogen human
      respiratory syncytial virus (hRSV). In a murine model of acute lower respiratory
      tract infection with hMPV, we demonstrate the accumulation of gamma interferon
      (IFN-gamma)-producing CD8+ T cells in the airways and lungs at day 7 post
      infection (p.i.), associated with cytotoxic T lymphocytes (CTLs) directed to an
      epitope of the M2-1 protein. This CTL immunity was accompanied by increased
      pulmonary expression of Th1 cytokines IFN-gamma and interleukin (IL)-12 and
      antiviral cytokines (IFN-beta), as well as chemokines Mip-1alpha, Mip-1beta, Mig,
      IP-10 and CX3CL1. There was also a moderate increase in Th2-type cytokines IL-4
      and IL-10 compared with uninfected mice. At 21 days p.i., a strong CTL response
      could be recalled from the spleen. A similar pattern of CTL induction to the
      homologous M2-1 CTL epitope of hRSV, and of cytokine/chemokine induction, was
      observed following infection with hRSV, highlighting similarities in the cellular
      immune response to the two related pathogens.

PMID- 20053826
TI  - Picture Quiz. The perils of a "FOOSH".

PMID- 20053827
TI  - Microscopic colitis in primary care.

PMID- 20053833
TI  - Searching for medical Rumpoles.

PMID- 20053835
TI  - Dutch probiotics study is criticised for its "design, approval, and conduct".

PMID- 20053836
TI  - Earlier help could reduce current "unsustainable" burden on NHS of alcohol.

PMID- 20053838
TI  - Functional embedding for the classification of gene expression profiles.
AB  - MOTIVATION: Low sample size n high-dimensional large p data with n<<p are
      commonly encountered in genomics and statistical genetics. Ill-conditioning of
      the variance-covariance matrix for such data renders the traditional multivariate
      data analytical approaches unattractive. On the other side, functional data
      analysis (FDA) approaches are designed for infinite-dimensional data and
      therefore may have potential for the analysis of large p data. We herein propose
      a functional embedding (FEM) technique, which exploits the interface between
      multivariate and functional data, aiming at borrowing strength across the sample
      through FDA techniques in order to resolve the difficulties caused by the high
      dimension p. RESULTS: Using pairwise dissimilarities among predictor variables,
      one obtains a univariate configuration of these covariates. This is interpreted
      as variable ordination that defines the domain of a suitable function space, thus
      leading to the FEM of the high-dimensional data. The embedding may then be
      followed by functional logistic regression for the classification of high
      dimensional multivariate data as an example for downstream analysis. The
      resulting functional classification is evaluated on several published gene
      expression array datasets and a mass spectrometric data, and is shown to compare
      favorably with various methods that have been employed previously for the
      classification of these high-dimensional gene expression profiles.

PMID- 20053839
TI  - GWAS analyzer: integrating genotype, phenotype and public annotation data for
      genome-wide association study analysis.
AB  - MOTIVATION: Genome-wide association studies are beginning to elucidate how our
      genetic differences contribute to susceptibility and severity of disease. While
      computational tools have previously been developed to support various aspects of
      genome-wide association studies, there is currently a need for informatics
      solutions that facilitate the integration of data from multiple sources. RESULTS:
      Here we present GWAS Analyzer, a database driven web-based tool that integrates
      genotype and phenotype data, association analysis results and genomic annotations
      from multiple public resources. GWAS Analyzer contains features for browsing
      these interrelated data, exploring phenotypic values by family or genotype, and
      filtering association results based on multiple criteria. The utility of the tool
      has been demonstrated by a genome-wide association study of human in vitro
      susceptibility to bacterial infection. GWAS Analyzer facilitated management of
      large sets of phenotype and genotype data, analysis of phenotypic variation and
      heritability, and most importantly, generation of a refined set of candidate
      single nucleotide polymorphisms (SNPs). The tool revealed a SNP that was
      experimentally validated to be associated with increased cell death among
      Salmonella infected HapMap cell lines.

PMID- 20053840
TI  - Disambiguating the species of biomedical named entities using natural language
      parsers.
AB  - MOTIVATION: Text mining technologies have been shown to reduce the laborious work
      involved in organizing the vast amount of information hidden in the literature.
      One challenge in text mining is linking ambiguous word forms to unambiguous
      biological concepts. This article reports on a comprehensive study on resolving
      the ambiguity in mentions of biomedical named entities with respect to model
      organisms and presents an array of approaches, with focus on methods utilizing
      natural language parsers. RESULTS: We build a corpus for organism disambiguation
      where every occurrence of protein/gene entity is manually tagged with a species
      ID, and evaluate a number of methods on it. Promising results are obtained by
      training a machine learning model on syntactic parse trees, which is then used to
      decide whether an entity belongs to the model organism denoted by a neighbouring
      species-indicating word (e.g. yeast). The parser-based approaches are also
      compared with a supervised classification method and results indicate that the
      former are a more favorable choice when domain portability is of concern. The
      best overall performance is obtained by combining the strengths of syntactic
      features and supervised classification. AVAILABILITY: The corpus and demo are
      available at http://www.nactem.ac.uk/deca_details/start.cgi, and the software is
      freely available as U-Compare components (Kano et al., 2009): NaCTeM Species Word
      Detector and NaCTeM Species Disambiguator. U-Compare is available at http://
      compare.org/

PMID- 20053841
TI  - Bioinformatics challenges for genome-wide association studies.
AB  - MOTIVATION: The sequencing of the human genome has made it possible to identify
      an informative set of >1 million single nucleotide polymorphisms (SNPs) across
      the genome that can be used to carry out genome-wide association studies (GWASs).
      The availability of massive amounts of GWAS data has necessitated the development
      of new biostatistical methods for quality control, imputation and analysis issues
      including multiple testing. This work has been successful and has enabled the
      discovery of new associations that have been replicated in multiple studies.
      However, it is now recognized that most SNPs discovered via GWAS have small
      effects on disease susceptibility and thus may not be suitable for improving
      health care through genetic testing. One likely explanation for the mixed results
      of GWAS is that the current biostatistical analysis paradigm is by design
      agnostic or unbiased in that it ignores all prior knowledge about disease
      pathobiology. Further, the linear modeling framework that is employed in GWAS
      often considers only one SNP at a time thus ignoring their genomic and
      environmental context. There is now a shift away from the biostatistical approach
      toward a more holistic approach that recognizes the complexity of the genotype
      phenotype relationship that is characterized by significant heterogeneity and
      gene-gene and gene-environment interaction. We argue here that bioinformatics has
      an important role to play in addressing the complexity of the underlying genetic
      basis of common human diseases. The goal of this review is to identify and
      discuss those GWAS challenges that will require computational methods.

PMID- 20053842
TI  - Xper2: introducing e-taxonomy.
AB  - MOTIVATION: Computer Aided Identification systems provide users with the
      resources to relate morpho-anatomic observations with taxa names and to
      subsequently access other knowledge about the organisms. They have the ability to
      manage descriptive data and make identifications through interactive keys. They
      are essential for both authors and users of biodiversity information. Xper(2)
      version 2.0 is one of the most user-friendly tools in its category and provides a
      complete environment dedicated to taxonomic management. AVAILABILITY: Xper(2)
      software can be freely downloaded at http://lis
      upmc.snv.jussieu.fr/lis/?q=en/resources/softwares/xper2

PMID- 20053843
TI  - dbTEU: a protein database of trace element utilization.
AB  - Biological trace elements are required for numerous biological processes and by
      all organisms. We describe a database, dbTEU (DataBase of Trace Element
      Utilization), that features known transporters and user proteins for five trace
      elements (copper, molybdenum, nickel, cobalt and selenium) and represents
      sequenced organisms from the three domains of life. The manually curated dbTEU
      currently includes approximately 16,500 proteins from >700 organisms, and offers
      interactive trace element, protein, organism and sequence search and browse
      tools. AVAILABILITY AND IMPLEMENTATION: dbTEU is freely available at
      http://gladyshevlab.bwh.harvard.edu/trace_element/

PMID- 20053844
TI  - CD-HIT Suite: a web server for clustering and comparing biological sequences.
AB  - CD-HIT is a widely used program for clustering and comparing large biological
      sequence datasets. In order to further assist the CD-HIT users, we significantly
      improved this program with more functions and better accuracy, scalability and
      flexibility. Most importantly, we developed a new web server, CD-HIT Suite, for
      clustering a user-uploaded sequence dataset or comparing it to another dataset at
      different identity levels. Users can now interactively explore the clusters
      within web browsers. We also provide downloadable clusters for several public
      databases (NCBI NR, Swissprot and PDB) at different identity levels.
      AVAILABILITY: Free access at http://cd-hit.org

PMID- 20053845
TI  - Neocortex network activation and deactivation states controlled by the thalamus.
AB  - Neocortex network activity varies from a desynchronized or activated state
      typical of arousal to a synchronized or deactivated state typical of quiescence.
      Such changes are usually attributed to the effects of neuromodulators released in
      the neocortex by nonspecific activating systems originating in basal forebrain
      and brain stem reticular formation. As a result, the only role attributed to
      thalamocortical cells projecting to primary sensory areas, such as barrel cortex,
      is to transmit sensory information. However, thalamocortical cells can undergo
      significant changes in spontaneous tonic firing as a function of state, although
      the role of such variations is unknown. Here we show that the tonic firing level
      of thalamocortical cells, produced by cholinergic and noradrenergic stimulation
      of the somatosensory thalamus in urethane-anesthetized rats, controls neocortex
      activation and deactivation. Thus in addition to its well-known role in the relay
      of sensory information, the thalamus can control the state of neocortex
      activation, which may complement the established roles in this regard of basal
      forebrain and brain stem nuclei. Because of the topographical organization of
      primary thalamocortical pathways, this mechanism provides a means by which area
      specific neocortical activation can occur, which may be useful for modality
      specific sensory processing or selective attention.

PMID- 20053846
TI  - Amphetamine increases persistent inward currents in human motoneurons estimated
      from paired motor-unit activity.
AB  - Recruitment and repetitive firing of spinal motoneurons depend on the activation
      of persistent inward calcium and sodium currents (PICs) that are in turn
      facilitated by serotonin and norepinephrine that arise primarily from the brain
      stem. Considering that in rats motoneuron PICs are greatly facilitated by
      increasing the presynaptic release of norepinephrine with amphetamine, we sought
      similar evidence for the modulation of PICs in human motoneurons. Pairs of motor
      units were recorded during a gradually increasing and then decreasing voluntary
      contraction. The firing frequency (F) of the lower-threshold (control) motor unit
      was used as an estimate of the synaptic input to the higher-threshold (test)
      motor unit. Generally, PICs are initiated during the recruitment of a motoneuron
      and subsequently provide a fixed depolarizing current that helps the synaptic
      input maintain firing until derecruitment. Thus the amplitude of the PIC in the
      test motor unit was estimated from the difference in synaptic input (DeltaF)
      needed to maintain minimal firing once the PIC was fully activated (measured at
      the time of test unit derecruitment) compared with the larger synaptic input
      required to initiate firing prior to full PIC activation (measured at the time of
      test unit recruitment; DeltaF = F(recruit) - F(derecruit)). Moreover, the
      activation time of the PIC was estimated as the minimal contraction duration
      needed to produce a maximal PIC (DeltaF). In five subjects, oral administration
      of amphetamine, but not placebo, increased the DeltaF by 62% [from 3.7 +/- 0.6 to
      6.0 +/- 0.8 (SD) imp/s, P = 0.001] and decreased the time needed to activate a
      maximal DeltaF from approximately 2 to 0.5 s. Both findings suggest that the
      endogenous facilitation of PICs from brain stem derived norepinephrine plays an
      important role in modulating human motoneuron excitability, readying motoneurons
      for rapid and sustained activity during periods of high arousal such as stress or
      fear.

PMID- 20053847
TI  - Tonically discharging genioglossus motor units show no evidence of rate coding
      with hypercapnia.
AB  - The genioglossus (GG) is considered the principle protrudor muscle of the human
      tongue. Unlike most skeletal muscles, GG electromyographic (EMG) activities are
      robustly preserved in sleep and thus may fulfill a critical role in preserving
      airway patency. Previous studies in human subjects also confirm that the GG EMG
      increases in response to chemoreceptor and mechanoreceptor stimulation. This
      increase occurs secondary to the recruitment of previously inactive motor units
      (MUs) and/or an increase in firing rate of already active MUs. Which strategy the
      nervous system uses when the synaptic drive onto GG motoneurons increases is not
      known. Here we report on GG whole muscle and tonic MU activities under conditions
      that mimic sleep, i.e., mild-moderate elevations in CO(2) (3% inspired CO(2) or
      the addition of a 1.0 l dead space) and elevated airway resistance. Based on
      previous work in rat, we hypothesized that mild hypercapnia would increase the
      firing rates of tonic MUs and that these effects would be further potentiated by
      a modest increase in airway resistance. Fine wire and tungsten microelectrodes
      were inserted into the GG to record whole muscle and single MU activities in 21
      subjects (13 women, 8 men; 20-55 yr). Either 3% inspired CO(2) or added dead
      space resulted in a 200-300% increase in the amplitude of both tonic and phasic
      components of the whole muscle GG EMG and a doubling of minute ventilation.
      Despite these changes, recordings obtained from a total of 84 tonically
      discharging GG single MUs provide no evidence of a change in firing rate under
      any of the conditions. On this basis we conclude that in healthy adults, the
      increase in the tonic component of the whole muscle GG EMG secondary to mild
      hypercapnia is due almost exclusively to the recruitment of previously inactive
      MUs.

PMID- 20053848
TI  - Applicability of white-noise techniques to analyzing motion responses.
AB  - Motion processing in visual neurons is often understood in terms of how they
      integrate light stimuli in space and time. These integrative properties, known as
      the spatiotemporal receptive fields (STRFs), are sometimes obtained using white
      noise techniques where a continuous random contrast sequence is delivered to each
      spatial location within the cell's field of view. In contrast, motion stimuli
      such as moving bars are usually presented intermittently. Here we compare the
      STRF prediction of a neuron's response to a moving bar with the measured response
      in second-order interneurons (L-neurons) of dragonfly ocelli (simple eyes). These
      low-latency neurons transmit sudden changes in intensity and motion information
      to mediate flight and gaze stabilization reflexes. A white-noise analysis is made
      of the responses of L-neurons to random bar stimuli delivered either every frame
      (densely) or intermittently (sparsely) with a temporal sequence matched to the
      bar motion stimulus. Linear STRFs estimated using the sparse stimulus were
      significantly better at predicting the responses to moving bars than the STRFs
      estimated using a traditional dense white-noise stimulus, even when second-order
      nonlinear terms were added. Our results strongly suggest that visual adaptation
      significantly modifies the linear STRF properties of L-neurons in dragonfly
      ocelli during dense white-noise stimulation. We discuss the ability to predict
      the responses of visual neurons to arbitrary stimuli based on white-noise
      analysis. We also discuss the likely functional advantages that adaptive
      receptive field structures provide for stabilizing attitude during hover and
      forward flight in dragonflies.

PMID- 20053850
TI  - Evaluation of Sensititre plates for identification of clinically relevant
      coagulase-negative staphylococci.
AB  - Coagulase-negative staphylococcus isolates were identified using Sensititre GPID
      plates and API strips (n = 156). For selected isolates, partial sequencing of the
      16S rRNA, sodA, and tuf genes was performed. The Sensititre plates correctly
      identified 68.9% of isolates, with a concordance of 86% for Staphylococcus
      haemolyticus and 73% for Staphylococcus epidermidis.

PMID- 20053849
TI  - Mechanisms and distribution of ion channels in retinal ganglion cells: using
      temperature as an independent variable.
AB  - Trains of action potentials of rat and cat retinal ganglion cells (RGCs) were
      recorded intracellularly across a temperature range of 7-37 degrees C. Phase
      plots of the experimental impulse trains were precision fit using
      multicompartment simulations of anatomically reconstructed rat and cat RGCs.
      Action potential excitation was simulated with a "Five-channel model" [Na,
      K(delayed rectifier), Ca, K(A), and K(Ca-activated) channels] and the nonspace
      clamped condition of the whole cell recording was exploited to determine the
      channels' distribution on the dendrites, soma, and proximal axon. At each
      temperature, optimal phase-plot fits for RGCs occurred with the same unique
      channel distribution. The "waveform" of the electrotonic current was found to be
      temperature dependent, which reflected the shape changes in the experimental
      action potentials and confirmed the channel distributions. The distributions are
      cell-type specific and adequate for soma and dendritic excitation with a safety
      margin. The highest Na-channel density was found on an axonal segment some 50-130
      microm distal to the soma, as determined from the temperature-dependent "initial
      segment-somadendritic (IS-SD) break." The voltage dependence of the gating rate
      constants remains invariant between 7 and 23 degrees C and between 30 and 37
      degrees C, but undergoes a transition between 23 and 30 degrees C. Both gating
      kinetic and ion-permeability Q10s remain virtually constant between 23 and 37
      degrees C (kinetic Q10s = 1.9-1.95; permeability Q10s = 1.49-1.64). The Q10s
      systematically increase for T <23 degrees C (kinetic Q10 = 8 at T = 8 degrees C).
      The Na channels were consistently "sleepy" (non-Arrhenius) for T <8 degrees C,
      with a loss of spiking for T <7 degrees C.

PMID- 20053851
TI  - Genetic relationships among reptilian and mammalian Campylobacter fetus strains
      determined by multilocus sequence typing.
AB  - Reptile Campylobacter fetus isolates and closely related strains causing human
      disease were characterized by multilocus sequence typing. They shared
      approximately 90% nucleotide sequence identity with classical mammalian C. fetus,
      and there was evidence of recombination among members of these two groups. The
      reptile group represents a possible separate genomospecies capable of infecting
      humans.

PMID- 20053852
TI  - Comprehensive analysis of a norovirus-associated gastroenteritis outbreak, from
      the environment to the consumer.
AB  - Noroviruses have been recognized to be the predominant agents of nonbacterial
      gastroenteritis outbreaks in humans, and their transmission via contaminated
      shellfish consumption has been demonstrated. Norovirus laboratory experiments,
      volunteer challenge studies, and community gastroenteritis outbreak
      investigations have identified human genetic susceptibility factors related to
      histo-blood group antigen expression. Following a banquet in Brittany, France, in
      February 2008, gastroenteritis cases were linked to oyster consumption. This
      study identified an association of the norovirus illnesses with histo-blood group
      expression, and oyster contamination with norovirus was confirmed by qualitative
      and quantitative analyses. The secretor phenotype was associated with illness,
      especially for the non-A subgroup. The study showed that, in addition to
      accidental climatic events that may lead to oyster contamination, illegal
      shellfish collection and trading are also risk factors associated with outbreaks.

PMID- 20053853
TI  - Evaluation of multiplex type-specific real-time PCR assays using the LightCycler
      and joint biological agent identification and diagnostic system platforms for
      detection and quantitation of adult human respiratory adenoviruses.
AB  - Every year, thousands of basic military trainees in each service of the U.S.
      Armed Forces experience acute respiratory disease. The majority of this disease
      burden results from infection with human adenoviruses. We designed single- and
      multiplex assays that detect and discriminate adenovirus types B3, E4, B7, B11,
      B14, and B21. A total of 116 oropharyngeal swab specimens obtained from patients
      at the Naval Health Research Center were used to validate the new assays. Type
      specific singleplex assays were designed and used independently to successfully
      identify 94 representative patient specimens. The lower limits of detection for
      our singleplex real-time PCR assays were calculated to be 50, 500, 500, 50, 50,
      and 50 genomic copies per reaction for human adenovirus type B3 (HAdV-B3), HAdV
      E4, HAdV-B7, HAdV-B11, HAdV-B14, and HAdV-B21, respectively. These were then
      multiplexed to increase efficiency and tested against singleplex assays using
      titrated controls. The HAdV-B3/B11 and HAdV-E4/B7 multiplex assays were as
      sensitive and specific as they were individually. The HAdV-B14/B21 multiplex
      assay was not as efficient at detecting HAdV-B14 as the singleplex assay.
      Interestingly, a statistically significant difference was found between the viral
      loads of HAdV-B14 and those of HAdV-B3, -E4, -B7, and -B21 (P < 0.001). The
      assays did not cross-react with other adenoviruses, influenza virus, respiratory
      syncytial virus, or respiratory disease-causing bacteria. These assays have the
      potential to be useful as clinical diagnostic tools for the detection of HAdV
      infection in adult populations.

PMID- 20053854
TI  - Multiplex real-time PCR assay for simultaneous quantification of BK polyomavirus,
      JC polyomavirus, and adenovirus DNA.
AB  - In recent years, virus-induced nephropathy caused mainly by BK polyomavirus
      (BKPyV), JC polyomavirus (JCPyV), and adenovirus has emerged as a problem in
      renal transplant patients. In the present study, we developed a multiplex real
      time PCR assay to quantify the viral load of BKPyV, JCPyV, and adenovirus
      simultaneously. The dynamic range covered at least 6 orders of magnitude. This
      system was specific and reproducible, even in the presence of large amounts of
      DNA of other viruses. To validate this assay, urine samples from 124 renal
      transplant patients and serum samples from 18 hemorrhagic cystitis patients after
      hematopoietic stem cell transplantation were examined. In the urine samples from
      renal transplant patients, BKPyV was detected in 28 patients (22.6%), JCPyV was
      detected in 51 patients (41.1%), and adenovirus was detected in 2 patients
      (1.6%). The maximum amounts of each virus detected were 2.7 x 10(9), 8.7 x 10(8),
      and 1.2 x 10(2) copies/ml, respectively. Decoy cells were observed in 31
      patients. The quantities of both BKPyV and JCPyV DNA were greater in samples with
      decoy cells. Two patients whose BKPyV viral loads exceeded 10(8) copies/ml had
      elevated serum creatinine levels and were diagnosed with BKPyV nephropathy based
      on graft biopsies. In serum samples from hemorrhagic cystitis patients, BKPyV,
      JCPyV, and adenovirus was detected in six, two, and three patients, respectively.
      Strong correlations were observed between the viral DNA copy numbers determined
      in the multiplex assays and those determined in single assays. Since this new
      assay is rapid, sensitive, and specific, it can be used for quantitative analyses
      of viruses in urine and serum samples after transplantation.

PMID- 20053855
TI  - Multiplex-PCR method for species identification of coagulase-positive
      staphylococci.
AB  - In veterinary medicine, coagulase-positive staphylococci (CoPS) other than
      Staphylococcus aureus have frequently been misidentified as being S. aureus
      strains, as they have several phenotypic traits in common. There has been no
      reliable method to distinguish among CoPS species in veterinary clinical
      laboratories. In the present study, we sequenced the thermonuclease (nuc) genes
      of staphylococcal species and devised a multiplex-PCR (M-PCR) method for species
      identification of CoPS by targeting the nuc gene locus. To evaluate sensitivity
      and specificity, we used this M-PCR method on 374 staphylococcal strains that had
      been previously identified to the species level by an hsp60 sequencing approach.
      We could successfully distinguish between S. aureus, S. hyicus, S. schleiferi, S.
      intermedius, S. pseudintermedius, and S. delphini groups A and B. The present
      method was both sensitive (99.8%) and specific (100%). Our M-PCR assay will allow
      the routine species identification of CoPS isolates from various animal species
      for clinical veterinary diagnosis.

PMID- 20053856
TI  - Performance of fusidic acid (CEM-102) susceptibility testing reagents: broth
      microdilution, disk diffusion, and Etest methods as applied to Staphylococcus
      aureus.
AB  - Fusidic acid (CEM-102) is an established antistaphylococcal agent that has been
      used in clinical practice for more than 4 decades. The activity of fusidic acid
      against 778 isolates of Staphylococcus aureus collected from U.S. (53.8% were
      methicillin-resistant S. aureus [MRSA]) and Canadian (46.5% were MRSA) medical
      centers was assessed to determine the intermethod accuracy of the Clinical and
      Laboratory Standards Institute (CLSI) and Etest methods. Broth microdilution MIC
      results were compared by scattergram analysis to zone diameters around
      commercially available 5- and 10-microg disks. Acceptable correlation (r = 0.74
      to 0.76) was observed for the two disk concentrations, and applying breakpoints
      of < or = 1 microg/ml (> or = 22 mm) for susceptibility (S) and > or = 4
      microg/ml (< or = 19 mm) for resistance (R) provided 99.9% absolute intermethod
      categorical agreement. Reference CLSI MIC versus Etest MIC results (r = 0.77; 728
      strains) showed 55.4% identical results and agreement of 99.7% +/- one log2
      dilution. The diagnostic susceptibility testing reagents (including Etest) for
      fusidic acid (CEM-102) performed at an excellent level of intermethod agreement
      for the proposed breakpoint criteria.

PMID- 20053857
TI  - Comparison of polyurethane foam to nylon flocked swabs for collection of
      secretions from the anterior nares in performance of a rapid influenza virus
      antigen test in a pediatric emergency department.
AB  - Rapid antigen testing of upper respiratory secretions collected with various swab
      types is often utilized for laboratory diagnoses of influenza virus infection.
      There are limited data on the effects of swab composition on test performance.
      This study compared the performance of the Quidel QuickVue Influenza A+B test on
      secretions from the anterior nares when a polyurethane foam swab was used for
      collection to that when a nylon flocked swab was used for collection. One hundred
      subjects who presented to a pediatric emergency department with symptoms
      suggestive of an influenza virus infection were recruited for the study. Foam and
      flocked swabs of the anterior nares were obtained from separate nares of each
      subject before a posterior nasopharyngeal swab was collected and placed into
      viral transport medium. The QuickVue test was performed directly on each swab
      type, and the results were compared to the results of reverse transcription-PCR
      (RT-PCR), direct fluorescent antibody (DFA) test, and viral culture performed on
      the transport medium. RT-PCR alone and DFA combined with culture were utilized as
      separate gold standards. There were 56 cases of influenza detected by RT-PCR; the
      QuickVue test was positive for 40 foam and 30 flocked swabs, for sensitivities of
      71% and 54%, respectively (P = 0.01). Similarly, there were 49 influenza cases
      detected by DFA and/or culture; the QuickVue test was positive for 38 foam and 30
      flocked swabs, for sensitivities of 78% and 61%, respectively (P = 0.13). This
      study suggests that polyurethane foam swabs perform better than nylon flocked
      swabs for the collection of secretions from anterior nares in the Quidel QuickVue
      Influenza A+B test.

PMID- 20053858
TI  - Acute cholecystitis caused by nontoxigenic Vibrio cholerae O1 Inaba.
AB  - A rare case of acute cholecystitis caused by serogroup O1 Vibrio cholerae in an
      83-year-old man is presented. His risk factors for cholecystitis included
      advanced age and previous abdominal surgeries. The patient had consumed raw
      oysters several days before presentation. The patient had a poor outcome after
      admission for this infection, likely due to his underlying illnesses that
      complicated his hospital course.

PMID- 20053859
TI  - High-throughput identification of bacteria and yeast by matrix-assisted laser
      desorption ionization-time of flight mass spectrometry in conventional medical
      microbiology laboratories.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) is suitable for high-throughput and rapid diagnostics at low costs
      and can be considered an alternative for conventional biochemical and molecular
      identification systems in a conventional microbiological laboratory. First, we
      evaluated MALDI-TOF MS using 327 clinical isolates previously cultured from
      patient materials and identified by conventional techniques (Vitek-II, API, and
      biochemical tests). Discrepancies were analyzed by molecular analysis of the 16S
      genes. Of 327 isolates, 95.1% were identified correctly to genus level, and 85.6%
      were identified to species level by MALDI-TOF MS. Second, we performed a
      prospective validation study, including 980 clinical isolates of bacteria and
      yeasts. Overall performance of MALDI-TOF MS was significantly better than
      conventional biochemical systems for correct species identification (92.2% and
      83.1%, respectively) and produced fewer incorrect genus identifications (0.1% and
      1.6%, respectively). Correct species identification by MALDI-TOF MS was observed
      in 97.7% of Enterobacteriaceae, 92% of nonfermentative Gram-negative bacteria,
      94.3% of staphylococci, 84.8% of streptococci, 84% of a miscellaneous group
      (mainly Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella
      [HACEK]), and 85.2% of yeasts. MALDI-TOF MS had significantly better performance
      than conventional methods for species identification of staphylococci and genus
      identification of bacteria belonging to HACEK group. Misidentifications by MALDI
      TOF MS were clearly associated with an absence of sufficient spectra from
      suitable reference strains in the MALDI-TOF MS database. We conclude that MALDI
      TOF MS can be implemented easily for routine identification of bacteria (except
      for pneumococci and viridans streptococci) and yeasts in a medical
      microbiological laboratory.

PMID- 20053860
TI  - Cytotoxic effects of Klebsiella oxytoca strains isolated from patients with
      antibiotic-associated hemorrhagic colitis or other diseases caused by infections
      and from healthy subjects.
AB  - Antibiotic-associated hemorrhagic colitis (AAHC) is associated with Klebsiella
      oxytoca. This study analyzed whether cytotoxic properties are linked to specific
      subtypes of K. oxytoca. Klebsiella isolates from stools of AAHC patients, healthy
      carriers, and diarrhea patients as well as from infections of other organs were
      investigated. Cytotoxic effects on human epithelial cells were limited to the
      species K. oxytoca and were not detectable for any other Klebsiella species.
      Isolates from AAHC patients and from stools showed the highest proportion of
      cytotoxic strains. Urinary or respiratory tract isolates exhibited no
      cytotoxicity. Macrorestriction profiling of strains revealed no genetic
      relationships of AAHC isolates or the cytotoxic phenotype but identified that
      different K. oxytoca strains with different cytotoxic behaviors may be prevalent
      in the same AAHC patient. Under laboratory conditions, cytotoxicity was maximally
      effective after exponential bacterial growth and then declined despite the
      continued viability of K. oxytoca cells in culture. Given its capacity to induce
      AAHC and that a high proportion of stool isolates tested cytotoxin positive, we
      argue that K. oxytoca should be considered an opportunistic pathogen if detected
      in stools. The ability to induce disease after antibiotic treatment most likely
      represents an overgrowth of the toxin-producing bacterium due to an alteration of
      the normal colonic microflora.

PMID- 20053861
TI  - Use of the normalized absorbance ratio as an internal standardization approach to
      minimize measurement error in enzyme-linked immunosorbent assays for diagnosis of
      human papillomavirus infection.
AB  - The serological detection of antibodies against human papillomavirus (HPV)
      antigens is a useful tool to determine exposure to genital HPV infection and in
      predicting the risk of infection persistence and associated lesions. Enzyme
      linked immunosorbent assays (ELISAs) are commonly used for seroepidemiological
      studies of HPV infection but are not standardized. Intra- and interassay
      performance variation is difficult to control, especially in cohort studies that
      require the testing of specimens over extended periods. We propose the use of
      normalized absorbance ratios (NARs) as a standardization procedure to control for
      such variations and minimize measurement error. We compared NAR and ELISA optical
      density (OD) values for the strength of the correlation between serological
      results for paired visits 4 months apart and HPV-16 DNA positivity in cervical
      specimens from a cohort investigation of 2,048 women tested with an ELISA using
      HPV-16 virus-like particles. NARs were calculated by dividing the mean blank
      subtracted (net) ODs by the equivalent values of a control serum pool included in
      the same plate in triplicate, using different dilutions. Stronger correlations
      were observed with NAR values than with net ODs at every dilution, with an
      overall reduction in nonexplained regression variability of 39%. Using logistic
      regression, the ranges of odds ratios of HPV-16 DNA positivity contrasting upper
      and lower quintiles at different dilutions and their averages were 4.73 to 5.47
      for NARs and 2.78 to 3.28 for net ODs, with corresponding significant
      improvements in seroreactivity-risk trends across quintiles when NARs were used.
      The NAR standardization is a simple procedure to reduce measurement error in
      seroepidemiological studies of HPV infection.

PMID- 20053863
TI  - Rapid identification and discrimination of Brucella isolates by use of real-time
      PCR and high-resolution melt analysis.
AB  - Definitive identification of Brucella species remains a challenge due to the high
      degree of genetic homology shared within the genus. We report the development of
      a molecular technique which utilizes real-time PCR followed by high-resolution
      melt (HRM) curve analysis to reliably type members of this genus. Using a panel
      of seven primer sets, we tested 153 Brucella spp. isolates with >99% accuracy
      compared to traditional techniques. This assay provides a useful diagnostic tool
      that can rapidly type Brucella isolates and has the potential to detect novel
      species. This approach may also prove helpful for clinical, epidemiological and
      veterinary investigations.

PMID- 20053862
TI  - Diversity of VacA intermediate region among Helicobacter pylori strains from
      several regions of the world.
AB  - Helicobacter pylori is known to be a major cause of gastric carcinoma and peptic
      ulceration. cagA positivity and vacA's signal regions and mid-regions are well
      characterized markers of H. pylori's virulence. Recently, an intermediate region
      has been identified as another strong marker of H. pylori-associated disease, and
      its i1 allele has been linked with severe diseases in colonized hosts. The goal
      of this study was to determine the prevalence of the intermediate alleles in H.
      pylori isolates from China, Turkey, and Uruguay and from U.S. Africans and to
      compare their distribution with other well-characterized virulence factors.
      Originally, 123 H. pylori strains were studied, but 3 were excluded due to the
      failure to amplify the intermediate region in these samples. Therefore, a total
      of 120 strains were analyzed: 30 Chinese isolates, 35 Turkish isolates, 30
      Uruguayan isolates, and 25 U.S. African isolates. The s type and the m type were
      determined by PCR amplification. The i type was identified by PCR amplification
      and DNA sequencing. CagA status was determined by PCR methodology. There was a
      strong correlation among CagA positivity, s1, and i1 in Chinese, U.S. African,
      and Uruguayan isolates, but less correlation among these markers in Turkish
      isolates. A new intermediate variant (i3) was identified in 25.7% of Turkish
      strains and 3.3% of the Chinese strains. In summary, the distribution of CagA
      positivity and s1 correlated with the i1 in the three populations, except in the
      Turkish population, which showed a disproportionate representation of the i3
      allele. Phylogenetic mapping confirmed the i-typing method previously defined and
      adopted for this study. The phylogenetic tree showed country-specific correlation
      with the intermediate region. Our results showed that the i1 allele is strongly
      associated with CagA positivity and the vacA s1 allele, suggesting its role as a
      virulence marker and potential predictor for clinical outcome.

PMID- 20053864
TI  - Iconic decay in schizophrenia.
AB  - Working memory impairment is considered a core deficit in schizophrenia, but the
      precise nature of this deficit has not been determined. Multiple lines of
      evidence implicate deficits at the encoding stage. During encoding, information
      is held in a precategorical sensory store termed iconic memory, a literal image
      of the stimulus with high capacity but rapid decay. Pathologically increased
      iconic decay could reduce the number of items that can be transferred into
      working memory before the information is lost and could thus contribute to the
      working memory deficit seen in the illness. The current study used a partial
      report procedure to test the hypothesis that patients with schizophrenia (n = 37)
      display faster iconic memory decay than matched healthy control participants (n =
      28). Six letters, arranged in a circle, were presented for 50 ms. Following a
      variable delay of 0-1000 ms, a central arrow cue indicated the item to be
      reported. In both patients and control subjects, recall accuracy decreased with
      increasing cue delay, reflecting decay of the iconic representation of the
      stimulus array. Patients displayed impaired memory performance across all cue
      delays, consistent with an impairment in working memory, but the rate of iconic
      memory decay did not differ between patients and controls. This provides clear
      evidence against faster loss of iconic memory representations in schizophrenia,
      ruling out iconic decay as an underlying source of the working memory impairment
      in this population. Thus, iconic decay rate can be added to a growing list of
      unimpaired cognitive building blocks in schizophrenia.

PMID- 20053865
TI  - Neuropsychological profiles in different at-risk states of psychosis: executive
      control impairment in the early--and additional memory dysfunction in the late-
      prodromal state.
AB  - Impairments in neuropsychological functioning have been described in subjects
      clinically at high risk for psychosis, but the specific cognitive deficits in
      different clinical high-risk groups remain to be elucidated. The German Research
      Network on Schizophrenia employs a heuristic 2-stage model: a putatively late
      prodromal state (LPS), characterized by the onset of attenuated positive or brief
      psychotic symptoms, and an early prodromal state (EPS), mainly characterized by
      the presence of basic symptoms, which are predictive for psychosis within the
      next 10 years. A total of 205 subjects met the criteria for either an EPS or an
      LPS of psychosis and were assessed with a comprehensive neuropsychological test
      battery. Neurocognitive profiles of high-risk groups were compared with data of
      87 healthy controls comparable with regard to gender, age, and premorbid verbal
      IQ. Patients in the LPS were impaired in all neurocognitive domains
      (memory/learning, executive control/processing speed, and working memory)
      examined, with memory being the worst. Deficits were less pronounced in patients
      in the EPS, with a specific deficit in the executive control/processing speed
      domain. Consistent with a progressive neurodevelopmental disorder, some cognitive
      abilities were already impaired in patients in the EPS, followed by further
      deterioration in the LPS. Specifically, deficits in executive control functioning
      were related to the presence of basic symptoms, indicating a vulnerability for
      psychosis. Memory deficits were associated with the onset of psychotic symptoms
      indicating further disease progression in the trajectory to psychosis and, thus,
      may be useful in predicting psychosis and targeting early intervention.

PMID- 20053866
TI  - Association of increased prenatal estrogen with risk factors for schizophrenia.
AB  - The author previously described a theoretical cause of schizophrenia based on the
      effects of estrogenic endocrine disruption. In the current review, the author
      describes how increased estrogen during pregnancy increases susceptibility to
      certain viral infections associated with increased risk for schizophrenia. The
      review further discusses how prenatal estrogen exposure could explain
      associations of schizophrenia with autoimmune diseases, urban environments, and
      stress. Based on the association of increased estrogen with schizophrenia risk
      factors, the author proposes increased prenatal estrogen as a unifying factor,
      perhaps the primary event, in the etiology of schizophrenia.

PMID- 20053867
TI  - Similar favorable outcome of pegfilgrastim overdose in patients with different
      age and underlying disease.

PMID- 20053868
TI  - Replicative senescence-associated gene expression changes in mesenchymal stromal
      cells are similar under different culture conditions.
AB  - BACKGROUND: Research on mesenchymal stromal cells has created high expectations
      for a variety of therapeutic applications. Extensive propagation to yield enough
      mesenchymal stromal cells for therapy may result in replicative senescence and
      thus hamper long-term functionality in vivo. Highly variable proliferation rates
      of mesenchymal stromal cells in the course of long-term expansions under varying
      culture conditions may already indicate different propensity for cellular
      senescence. We hypothesized that senescence-associated regulated genes differ in
      mesenchymal stromal cells propagated under different culture conditions. DESIGN
      AND METHODS: Human bone marrow-derived mesenchymal stromal cells were cultured
      either by serial passaging or by a two-step protocol in three different growth
      conditions. Culture media were supplemented with either fetal bovine serum in
      varying concentrations or pooled human platelet lysate. RESULTS: All mesenchymal
      stromal cell preparations revealed significant gene expression changes upon long
      term culture. Especially genes involved in cell differentiation, apoptosis and
      cell death were up-regulated, whereas genes involved in mitosis and proliferation
      were down-regulated. Furthermore, overlapping senescence-associated gene
      expression changes were found in all mesenchymal stromal cell preparations.
      CONCLUSIONS: Long-term cell growth induced similar gene expression changes in
      mesenchymal stromal cells independently of isolation and expansion conditions. In
      advance of therapeutic application, this panel of genes might offer a feasible
      approach to assessing mesenchymal stromal cell quality with regard to the state
      of replicative senescence.

PMID- 20053869
TI  - Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory
      multiple myeloma: results of a multicenter phase I/II trial.
AB  - BACKGROUND: Defibrotide is a novel orally bioavailable polydisperse
      oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice,
      defibrotide showed activity in human myeloma xenografts. This phase I/II study
      was conducted to identify the most appropriate dose of defibrotide in combination
      with melphalan, prednisone and thalidomide in patients with relapsed and
      relapsed/refractory multiple myeloma, and to determine its safety and
      tolerability as part of this regimen. DESIGN AND METHODS: This was a phase I/II,
      multicenter, dose-escalating, non-comparative, open label study. Oral melphalan
      was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5
      mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously.
      Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on
      days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. RESULTS: Twenty-four patients with
      relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was
      observed. In all patients, the complete response plus very good partial response
      rate was 9%, and the partial response rate was 43%. The 1-year progression-free
      survival and 1-year overall survival rates were 34% and 90%, respectively. The
      most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia,
      anemia and fatigue. Deep vein thrombosis was reported in only one patient.
      CONCLUSIONS: This combination of melphalan, prednisone and thalidomide together
      with defibrotide showed anti-tumor activity with a favorable tolerability. The
      maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4
      followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the
      role of this regimen and to evaluate the combination of defibrotide with new
      drugs.

PMID- 20053870
TI  - Autoimmunity and the risk of myeloproliferative neoplasms.
AB  - The causes of myeloproliferative neoplasm (MPN) are unknown. We conducted a large
      population-based study including 11,039 myeloproliferative neoplasm patients and
      43,550 matched controls with the aim of assessing the associations between a
      personal history of a broad span of autoimmune diseases and subsequent risk of
      myeloproliferative neoplasm. We found a prior history of any autoimmune disease
      to be associated with a significantly increased risk of myeloproliferative
      neoplasms (odds ratio (OR)=1.2; 95% confidence interval (CI) 1.0-1.3; P=0.021).
      Specifically, we found an increased risk of MPNs associated with a prior immune
      thrombocytopenic purpura (2.9; 1.7-7.2), Crohn's disease (1.8; 1.1-3.0),
      polymyalgia rheumatica (1.7; 1.2-2.5), giant cell arteritis (5.9; 2.4-14.4),
      Reiter's syndrome (15.9; 1.8-142) and aplastic anemia (7.8; 3.7-16.7). The risk
      of myeloproliferative neoplasms associated with prior autoimmune diseases is
      modest but statistically significant. Future studies are needed to unravel the
      effects of these autoimmune diseases themselves, their treatment, or common
      genetic susceptibility.

PMID- 20053871
TI  - Prospective cardiopulmonary screening program to detect chronic thromboembolic
      pulmonary hypertension in patients after acute pulmonary embolism.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension after pulmonary
      embolism is associated with high morbidity and mortality. Understanding the
      incidence of chronic thromboembolic pulmonary hypertension after pulmonary
      embolism is important for evaluating the need for screening but is also a subject
      of debate because of different inclusion criteria among previous studies. We
      determined the incidence of chronic thromboembolic pulmonary hypertension after
      acute pulmonary embolism and the utility of a screening program for this disease.
      DESIGN AND METHODS: We conducted a cohort screening study in an unselected series
      of consecutive patients (n=866) diagnosed with acute pulmonary embolism between
      January 2001 and July 2007. All patients who had not been previously diagnosed
      with pulmonary hypertension (PH) and had survived until study inclusion were
      invited for echocardiography. Patients with echocardiographic suspicion of PH
      underwent complete work-up for chronic thromboembolic pulmonary hypertension,
      including ventilation-perfusion scintigraphy and right heart catheterization.
      RESULTS: After an average follow-up of 34 months of all 866 patients, PH was
      diagnosed in 19 patients by routine clinical care and in 10 by our screening
      program; 4 patients had chronic thromboembolic pulmonary hypertension, all
      diagnosed by routine clinical care. The cumulative incidence of chronic
      thromboembolic pulmonary hypertension after all cause pulmonary embolism was
      0.57% (95% confidence interval [CI] 0.02-1.2%) and after unprovoked pulmonary
      embolism 1.5% (95% CI 0.08-3.1%). CONCLUSIONS: Because of the low incidence of
      chronic thromboembolic pulmonary hypertension after pulmonary embolism and the
      very low yield of the echocardiography based screening program, wide scale
      implementation of prolonged follow-up including echocardiography of all patients
      with pulmonary embolism to detect chronic thromboembolic pulmonary hypertension
      does not seem to be warranted.

PMID- 20053872
TI  - Comparison of Recombinant Proteins from Schistosoma japonicum for Schistosomiasis
      Diagnosis.
AB  - The most important animal reservoirs of Schistosoma japonicum in China are
      bovines. Diagnosis and control of bovine schistosomiasis is critical for reducing
      the prevalence of the disease. We screened defined diagnostic antigens that have
      the potential to increase the sensitivity and specificity of serological assays
      and to distinguish between active and prior infections. Five recombinant proteins
      with the potential to be diagnostic antigens were compared to the native soluble
      egg antigen preparation by enzyme-linked immunosorbent assay (ELISA). We
      evaluated the potentials of the recombinant proteins for discriminating active
      from prior infections, as well as the therapeutic efficacy of the established
      ELISA technique.

PMID- 20053873
TI  - Immunogenicity of a live recombinant Salmonella enterica serovar typhimurium
      vaccine expressing pspA in neonates and infant mice born from naive and immunized
      mothers.
AB  - We are developing a Salmonella vectored vaccine to prevent infant pneumonia and
      other diseases caused by Streptococcus pneumoniae. One prerequisite for achieving
      this goal is to construct and evaluate new recombinant attenuated Salmonella
      vaccine (RASV) strains suitable for use in neonates and infants. Salmonella
      enterica serovar Typhimurium strain chi9558(pYA4088) specifies delivery of the
      pneumococcal protective antigen PspA and can protect adult mice from challenge
      with S. pneumoniae. This strain is completely safe for oral delivery to day-old
      and infant mice. Here we assess the colonizing ability, immunogenicity, and
      protective efficacy of chi9558(pYA4088) in neonatal mice. Colonization was
      assessed in mice 0, 2, 4, or 7 days of age after oral inoculation. In the
      presence of maternal antibodies, the colonization of lymphoid tissues was
      delayed, but the immune responses were enhanced in mice born to immunized
      mothers. Both oral and intranasal routes were used to assess immunogenicity. All
      orally or intranasally immunized neonatal and infant mice born to either
      immunized or naive mothers developed PspA-specific mucosal and systemic immune
      responses. Mice born to immunized mothers produced higher titers of PspA-specific
      antibodies in the blood and mucosa and greater numbers of PspA-specific
      interleukin-4 (IL-4)-secreting cells than mice born to naive mothers. More
      importantly, mice born to immune mothers showed a significant increase in
      protection against S. pneumoniae challenge. These results suggest that strain
      chi9558(pYA4088) can circumvent some of the limitations of the immature immune
      system in neonatal and infant mice, generating enhanced protective immune
      responses in the presence of maternal antibodies.

PMID- 20053874
TI  - Construction of recombinant attenuated Salmonella enterica serovar typhimurium
      vaccine vector strains for safety in newborn and infant mice.
AB  - Recombinant bacterial vaccines must be safe, efficacious, and well tolerated,
      especially when administered to newborns and infants to prevent diseases of early
      childhood. Many means of attenuation have been shown to render vaccine strains
      susceptible to host defenses or unable to colonize lymphoid tissue effectively,
      thus decreasing their immunogenicity. We have constructed recombinant attenuated
      Salmonella vaccine strains that display high levels of attenuation while
      retaining the ability to induce high levels of immunogenicity and are well
      tolerated in high doses when administered to infant mice as young as 24 h old.
      The strains contain three means of regulated delayed attenuation, as well as a
      constellation of additional mutations that aid in enhancing safety, regulate
      antigen expression, and reduce disease symptoms commonly associated with
      Salmonella infection. The vaccine strains are well tolerated when orally
      administered to infant mice 24 h old at doses as high as 3.5 x 10(8) CFU.

PMID- 20053876
TI  - Extreme percentiles of the 2000 Centers for Disease Control and Prevention BMI
      chart and the LMS method.

PMID- 20053875
TI  - Humoral immune responses against the Mycobacterium tuberculosis 38-kilodalton,
      MTB48, and CFP-10/ESAT-6 antigens in tuberculosis.
AB  - The diagnosis of smear-negative and culture-negative patients with active
      tuberculosis (TB) is challenging. The detection of Mycobacterium tuberculosis
      specific antibodies in human sera has been an important diagnostic aid. However,
      detection of antibody responses to a single antigen usually has a low sensitivity
      for diagnosis of TB. In this study, humoral immune responses against recombinant
      M. tuberculosis 38-kDa, MTB48, and CFP-10/ESAT-6 (culture filtrate protein 10/6
      kDa early secreted antigen target of M. tuberculosis) antigens in 250 Chinese TB
      patients and 260 healthy subjects were evaluated by an enzyme-linked
      immunosorbent assay (ELISA). The levels of antibodies against those antigens in
      TB patients, even in bacterium-negative ones, were significantly higher than
      those in healthy subjects (P < 0.001). The serodiagnostic sensitivities to detect
      antibodies against individual antigens, i.e., recombinant M. tuberculosis 38-kDa,
      MTB48, and CFP-10/ESAT-6 antigens, in TB patients were 73.6%, 73.2%, and 60.4%,
      respectively, with specificities of 85.4%, 77.7%, and 73.8%, respectively.
      Importantly, the sensitivity to positively detect humoral responses to one of the
      antigens increased further. Our data suggest that the humoral immune responses to
      M. tuberculosis antigens in TB patients are heterogeneous. The 38-kDa, MTB48, and
      CFP-10/ESAT-6 antigens can be used as the cocktail antigens in the serodiagnosis
      of active TB, especially for smear- or culture-negative TB cases.

PMID- 20053877
TI  - Reference curves for triceps and subscapular skinfold thicknesses in US children
      and adolescents.
AB  - BACKGROUND: Skinfold thicknesses have long been considered important and valid
      measurements of subcutaneous fat. Nevertheless, there are no current skinfold
      reference data for US children and adolescents. OBJECTIVE: We developed new
      percentile reference curves for triceps and subscapular skinfold thicknesses by
      using the same national samples as those included in the reference curves for
      body mass index (BMI) in the Centers for Disease Control and Prevention 2000
      Growth Charts. DESIGN: We included triceps and subscapular skinfold-thickness
      measurements for 32,783 individuals who also had complete data for BMI. The LMS
      method was used to derive 10 smoothed skinfold-thickness percentile reference
      curves and to generate the L, M, and S parameters that allow the calculation of
      standardized z scores. RESULTS: The new reference curves exhibit established age-
      and sex-related patterns of development, including dramatic prepubescent
      increases in subcutaneous fatness in boys at the highest percentiles. Comparisons
      of smoothed medians for race-ethnicity groups confirm greater subcutaneous
      fatness in white children than in black age mates at the triceps site but similar
      median subscapular skinfold thicknesses. Median skinfold thicknesses for children
      considered overweight (> or =85th percentile) or obese (> or =95th percentile) on
      the basis of BMI cutoffs do not follow closely the skinfold percentile reference
      channels across age, especially in boys, which suggests a certain degree of
      independence between BMI and skinfold thickness at the upper extremes of the BMI
      distribution. CONCLUSIONS: The age- and sex-standardized skinfold percentiles and
      z scores will be appropriate for a wide range of research applications that
      consider measures of subcutaneous fat. Because they were developed by using the
      same children as those used for the 2000 BMI curves of the Centers for Disease
      Control and Prevention, they provide an important new complementary assessment
      tool that should be appropriate for almost all US children and adolescents.

PMID- 20053878
TI  - Feeding preterm infants milk with a higher dose of docosahexaenoic acid than that
      used in current practice does not influence language or behavior in early
      childhood: a follow-up study of a randomized controlled trial.
AB  - BACKGROUND: The visual and mental development of preterm infants improved after
      feeding them milk enriched with docosahexaenoic acid (DHA) in amounts matching
      the fetal accretion rate. OBJECTIVE: The objective was to evaluate whether
      feeding preterm infants milk with a higher DHA content than that used in current
      practice influences language or behavior in early childhood. DESIGN: This was a
      follow-up study in a subgroup of infants enrolled in the DINO (Docosahexaenoic
      acid for the Improvement in Neurodevelopmental Outcome) trial. In a double-blind
      randomized controlled trial, infants born at <33 wk of gestation were fed milk
      containing 1% of total fatty acids as DHA (higher-DHA group) or approximately
      0.3% DHA (control group) until reaching full-term equivalent age. The longer-term
      effects of the intervention on language, behavior, and temperament were measured
      by using the MacArthur Communicative Development Inventory (MCDI) at 26-mo
      corrected age, the Strengths and Difficulties Questionnaire (SDQ), and the Short
      Temperament Scale for Children (STSC) between 3- and 5-y corrected age. RESULTS:
      Mean (+/-SD) MCDI scores did not differ significantly (adjusted P = 0.8) between
      the higher-DHA group (308 +/- 179, n = 60) and the control group (316 +/- 192, n
      = 67) per the Vocabulary Production subscale. Composite scores on the SDQ and
      STSC did not differ between the higher-DHA group and the control group [SDQ Total
      Difficulties: higher-DHA group (10.3 +/- 6.0, n = 61), control group (9.5 +/-
      5.5, n = 64), adjusted P = 0.5; STSC score: higher-DHA group (3.1 +/- 0.7, n =
      61), control group (3.0 +/- 0.7, n = 64), adjusted P = 0.3]. CONCLUSIONS: Feeding
      preterm infants milk containing 3 times the standard amount of DHA did not result
      in any clinically meaningful change to language development or behavior when
      assessed in early childhood. Whether longer-term effects of dietary DHA
      supplementation can be detected remains to be assessed. This trial was registered
      with the Australia and New Zealand Clinical Trial Registry at www.anzctr.org.au
      as 12606000327583.

PMID- 20053879
TI  - Exercise and ambient temperature may influence energy balance via satiation
      processes.

PMID- 20053880
TI  - Maternal macronutrient and energy intakes in pregnancy and offspring intake at 10
      y: exploring parental comparisons and prenatal effects.
AB  - BACKGROUND: High maternal dietary intakes in pregnancy may lead to increased
      fetal growth and program neuroendocrine pathways that result in greater appetite,
      energy intake, and adiposity in offspring later in life. Few prospective dietary
      studies have explored this relation. OBJECTIVE: The objective was to assess
      associations of maternal dietary intake in pregnancy and maternal and paternal
      dietary intake postnatally with child dietary intake and adiposity. DESIGN:
      Dietary intakes of energy, protein, total fat, and carbohydrate were assessed
      prospectively in mothers during pregnancy, in mothers and their partners at 47 mo
      postnatally, and in children at 10 y (n = 5717 mother-child pairs prenatally,
      5593 mother-child pairs postnatally, and 3009 father-child pairs). Child body
      composition was assessed at 9 and 11 y (n = 5725). RESULTS: Maternal dietary
      intakes of protein, fat (when adjusted for energy intake), and carbohydrate in
      pregnancy were positively associated with child dietary intakes of the same
      nutrients, and these associations were greater than those observed for paternal
      dietary intake, which was not strongly associated with offspring diet.
      Associations of maternal prenatal-offspring intakes were stronger than those of
      maternal postnatal-offspring intakes for protein and fat. Greater child energy
      and macronutrient intakes were only associated with greater adiposity in children
      when adjusted for potential energy underreporting. Maternal diet during pregnancy
      was not associated with offspring adiposity or lean mass. CONCLUSION: The
      stronger prenatal maternal associations with child dietary intake, particularly
      protein and fat, compared with both paternal intake associations and maternal
      postnatal intake associations provide some evidence for in utero programming of
      offspring appetite by maternal intake during pregnancy.

PMID- 20053882
TI  - Quantitative comparison of glutamatergic and GABAergic synaptic vesicles unveils
      selectivity for few proteins including MAL2, a novel synaptic vesicle protein.
AB  - Synaptic vesicles (SVs) store neurotransmitters and release them by exocytosis.
      The vesicular neurotransmitter transporters discriminate which transmitter will
      be sequestered and stored by the vesicles. However, it is unclear whether the
      neurotransmitter phenotype of SVs is solely defined by the transporters or
      whether it is associated with additional proteins. Here we have compared the
      protein composition of SVs enriched in vesicular glutamate (VGLUT-1) and GABA
      transporters (VGAT), respectively, using quantitative proteomics. Of >450
      quantified proteins, approximately 50 were differentially distributed between the
      populations, with only few of them being specific for SVs. Of these, the most
      striking differences were observed for the zinc transporter ZnT3 and the vesicle
      proteins SV2B and SV31 that are associated preferentially with VGLUT-1 vesicles,
      and for SV2C that is associated mainly with VGAT vesicles. Several additional
      proteins displayed a preference for VGLUT-1 vesicles including, surprisingly,
      synaptophysin, synaptotagmins, and syntaxin 1a. Moreover, MAL2, a membrane
      protein of unknown function distantly related to synaptophysins and SCAMPs,
      cofractionated with VGLUT-1 vesicles. Both subcellular fractionation and
      immunolocalization at the light and electron microscopic level revealed that MAL2
      is a bona-fide membrane constituent of SVs that is preferentially associated with
      VGLUT-1-containing nerve terminals. We conclude that SVs specific for different
      neurotransmitters share the majority of their protein constituents, with only few
      vesicle proteins showing preferences that, however, are nonexclusive, thus
      confirming that the vesicular transporters are the only components essential for
      defining the neurotransmitter phenotype of a SV.

PMID- 20053883
TI  - ColQ controls postsynaptic differentiation at the neuromuscular junction.
AB  - CollagenQ (ColQ) plays an important structural role at vertebrate neuromuscular
      junctions (NMJs) by anchoring and accumulating acetylcholinesterase (AChE) in the
      extracellular matrix (ECM). Moreover, ColQ interacts with perlecan/dystroglycan
      and the muscle-specific receptor tyrosine kinase (MuSK), key molecules in the NMJ
      formation. MuSK promotes acetylcholine receptor (AChR) clustering in a process
      mediated by rapsyn, a cytoplasmic protein that stimulates AChR packing in
      clusters and regulates synaptic gene transcription. Here, we investigated a
      regulatory role for ColQ by comparing the clustering and expression of synaptic
      proteins in wild type and ColQ-deficient muscle cells in culture and at NMJ. We
      show first that AChR clusters are smaller and more densely packed in the absence
      of ColQ both in vitro and in vivo. Second, we find that like AChRs and rapsyn,
      MuSK mRNA levels are increased in cultured cells but not in muscles lacking ColQ.
      However, membrane-bound MuSK is decreased both in vitro and in vivo suggesting
      that ColQ controls MuSK sorting or stabilization in the muscle membrane. In line
      with this, our data show that activation of the MuSK signaling pathway is altered
      in the absence of ColQ leading to (1) perturbation of AChR clustering and/or beta
      AChR subunit phosphorylation and (2) modifications of AChR mRNA level due to the
      lack of ColQ-MuSK interaction. Together, our results demonstrate that ColQ, in
      addition to its structural role, has important regulatory functions at the
      synapse by controlling AChR clustering and synaptic gene expression through its
      interaction with MuSK.

PMID- 20053884
TI  - Firing and cellular properties of V2a interneurons in the rodent spinal cord.
AB  - Previous studies have shown that a group of ventrally located neurons, designated
      V2a interneurons, play a key role in maintaining locomotor rhythmicity and in
      ensuring appropriate left-right alternation during locomotion (Crone et al.,
      2008, 2009). These V2a interneurons express the transcription factor Chx10. The
      aim of the present study was to characterize the locomotor-related activity of
      individual V2a interneurons, their cellular properties, and their detailed
      anatomical attributes in Chx10-GFP mice. A dorsal horn-removed preparation was
      developed to allow for visual whole-cell patch recordings from V2a interneurons
      along the entire lumbar spinal cord while at the same time leaving enough of the
      spinal cord intact to generate fictive locomotion. During drug-evoked locomotor
      like activity, a large proportion of Chx10 cells showed rhythmic firing or
      membrane potential fluctuations related to either flexor or extensor activity in
      every lumbar segment. Chx10 cells received predominantly rhythmic excitatory
      input. Chx10 neurons displayed a wide variety of firing and potential
      rhythmogenic properties. However, none of these properties was obviously related
      to the observed rhythmicity during locomotor-like activity. In dual recordings,
      we found no evidence of Chx10 neuron interconnectivity. Intracellular fills
      revealed diverse projection patterns with most Chx10 interneurons being local
      with projections to the central pattern generator and motor neuron regions of the
      spinal cord and others with long ascending and/or descending branches. These data
      are compatible with V2a neurons having a role in regulating segmental left-right
      alternation and ipsilateral motor neuron firing with little effect on rhythm
      generation.

PMID- 20053886
TI  - Comparing the neural basis of monetary reward and cognitive feedback during
      information-integration category learning.
AB  - The dopaminergic system is known to play a central role in reward-based learning
      (Schultz, 2006), yet it was also observed to be involved when only cognitive
      feedback is given (Aron et al., 2004). Within the domain of information
      integration category learning, in which information from several stimulus
      dimensions has to be integrated predecisionally (Ashby and Maddox, 2005), the
      importance of contingent feedback is well established (Maddox et al., 2003). We
      examined the common neural correlates of reward anticipation and prediction error
      in this task. Sixteen subjects performed two parallel information-integration
      tasks within a single event-related functional magnetic resonance imaging session
      but received a monetary reward only for one of them. Similar functional areas
      including basal ganglia structures were activated in both task versions. In
      contrast, a single structure, the nucleus accumbens, showed higher activation
      during monetary reward anticipation compared with the anticipation of cognitive
      feedback in information-integration learning. Additionally, this activation was
      predicted by measures of intrinsic motivation in the cognitive feedback task and
      by measures of extrinsic motivation in the rewarded task. Our results indicate
      that, although all other structures implicated in category learning are not
      significantly affected by altering the type of reward, the nucleus accumbens
      responds to the positive incentive properties of an expected reward depending on
      the specific type of the reward.

PMID- 20053885
TI  - Ca2+/calmodulin-dependent protein kinase II alpha is required for the initiation
      and maintenance of opioid-induced hyperalgesia.
AB  - Repeated administration of opioids not only leads to tolerance and dependence,
      but also results in nociceptive enhancement called opioid-induced hyperalgesia
      (OIH). Nociceptive mediators involved in OIH generation remain poorly understood.
      In the present study, we tested the hypothesis that Ca(2+)/calmodulin-depent
      protein kinase II (CaMKIIalpha) is critical for OIH. Opioid-induced hyperalgesia
      was produced by repeated morphine administration or pellet implantation in mice.
      Correlating with the development of tactile allodynia and thermal hyperalgesia,
      spinal CaMKIIalpha activity was significantly increased in OIH. KN93, a CaMKII
      inhibitor, dose- and time-dependently reversed OIH and CaMKII activation without
      impairing locomotor coordination. To elucidate the specific CaMKII isoform
      involved, we targeted CaMKIIalpha by using small interfering RNA and demonstrated
      that knockdown of spinal CaMKIIalpha attenuated OIH. Furthermore, morphine failed
      to induce OIH in CaMKIIalpha(T286A) point mutant mice, although wild-type
      littermate mice developed robust OIH after repeated treatments with morphine.
      These data implicate, for the first time, an essential role of CaMKIIalpha as a
      cellular mechanism leading to and maintaining opioid-induced hyperalgesia.

PMID- 20053887
TI  - Delayed intrinsic activation of an NMDA-independent CaM-kinase II in a critical
      time window is necessary for late consolidation of an associative memory.
AB  - Calcium/calmodulin-dependent kinases (CaM-kinases) are central to various forms
      of long-term memory (LTM) in a number of evolutionarily diverse organisms.
      However, it is still largely unknown what contributions specific CaM-kinases make
      to different phases of the same specific type of memory, such as acquisition, or
      early, intermediate, and late consolidation of associative LTM after classical
      conditioning. Here, we investigated the involvement of CaM-kinase II (CaMKII) in
      different phases of associative LTM induced by single-trial reward classical
      conditioning in Lymnaea, a well established invertebrate experimental system for
      studying molecular mechanisms of learning and memory. First, by using a general
      CaM-kinase inhibitor, KN-62, we found that CaM-kinase activation was necessary
      for acquisition and late consolidation, but not early or intermediate
      consolidation or retrieval of LTM. Then, we used Western blot-based
      phosphorylation assays and treatment with CaMKIINtide to identify CaMKII as the
      main CaM-kinase, the intrinsic activation of which, in a critical time window (
      approximately 24 h after learning), is central to late consolidation of LTM.
      Additionally, using MK-801 and CaMKIINtide we found that acquisition was
      dependent on both NMDA receptor and CaMKII activation. However, unlike
      acquisition, CaMKII-dependent late memory consolidation does not require the
      activation of NMDA receptors. Our new findings support the notion that even
      apparently stable memory traces may undergo further molecular changes and
      identify NMDA-independent intrinsic activation of CaMKII as a mechanism
      underlying this "lingering consolidation." This process may facilitate the
      preservation of LTM in the face of protein turnover or active molecular processes
      that underlie forgetting.

PMID- 20053888
TI  - Prefrontal-related functional connectivities within the default network are
      modulated by COMT val158met in healthy young adults.
AB  - Previous studies have supported the concept that the default network is an
      intrinsic brain system that participates in internal modes of cognition. Neural
      activity and connectivity within the default network, which are correlated with
      cognitive ability even at rest, may be plausible intermediate phenotypes that
      will enable us to understand the genetic mechanisms of individuals' cognitive
      function or the risk for genetic brain diseases. Using resting functional
      magnetic resonance imaging and imaging genetic paradigms, we investigated whether
      individual default network connectivity was modulated by COMT val(158)met in 57
      healthy young subjects. Compared with COMT heterozygous individuals, homozygous
      val individuals showed significantly decreased prefrontal-related connectivities,
      which primarily occurred between prefrontal regions and the posterior
      cingulate/restrosplenial cortices. Further analyses of the topological
      characteristics of the default network showed homozygous val individuals had
      significantly fewer node degrees in the prefrontal regions. This finding may
      partially elucidate previous reports that the COMT val variant is associated with
      inefficient prefrontal information processing and poor cognitive performance. Our
      findings suggest that default network connectivity that involves the prefrontal
      cortex is modulated by COMT val(158)met through differential effects on
      prefrontal dopamine levels.

PMID- 20053889
TI  - Mechanisms for adjusting interaural time differences to achieve binaural
      coincidence detection.
AB  - Understanding binaural perception requires detailed analyses of the neural
      circuitry responsible for the computation of interaural time differences (ITDs).
      In the avian brainstem, this circuit consists of internal axonal delay lines
      innervating an array of coincidence detector neurons that encode external ITDs.
      Nucleus magnocellularis (NM) neurons project to the dorsal dendritic field of the
      ipsilateral nucleus laminaris (NL) and to the ventral field of the contralateral
      NL. Contralateral-projecting axons form a delay line system along a band of NL
      neurons. Binaural acoustic signals in the form of phase-locked action potentials
      from NM cells arrive at NL and establish a topographic map of sound source
      location along the azimuth. These pathways are assumed to represent a circuit
      similar to the Jeffress model of sound localization, establishing a place code
      along an isofrequency contour of NL. Three-dimensional measurements of axon
      lengths reveal major discrepancies with the current model; the temporal offset
      based on conduction length alone makes encoding of physiological ITDs impossible.
      However, axon diameter and distances between Nodes of Ranvier also influence
      signal propagation times along an axon. Our measurements of these parameters
      reveal that diameter and internode distance can compensate for the temporal
      offset inferred from axon lengths alone. Together with other recent studies,
      these unexpected results should inspire new thinking on the cellular biology,
      evolution, and plasticity of the circuitry underlying low-frequency sound
      localization in both birds and mammals.

PMID- 20053890
TI  - Neonatal cerebral hypoxia-ischemia impairs plasticity in rat visual cortex.
AB  - Ocular dominance plasticity (ODP) following monocular deprivation (MD) is a model
      of activity-dependent neural plasticity that is restricted to an early critical
      period regulated by maturation of inhibition. Unique developmental plasticity
      mechanisms may improve outcomes following early brain injury. Our objective was
      to determine the effects of neonatal cerebral hypoxia-ischemia (HI) on ODP. The
      rationale extends from observations that neonatal HI results in death of subplate
      neurons, a transient population known to influence development of inhibition. In
      rodents subjected to neonatal HI and controls, maps of visual response were
      derived from optical imaging during the critical period for ODP and changes in
      the balance of eye-specific response following MD were measured. In controls, MD
      results in a shift of the ocular dominance index (ODI) from a baseline of 0.15 to
      -0.10 (p < 0.001). Neonatal HI with moderate cortical injury impairs this shift,
      ODI = 0.14 (p < 0.01). Plasticity was intact in animals with mild injury and in
      those exposed to hypoxia alone. Neonatal HI resulted in decreased parvalbumin
      expression in hemispheres receiving HI compared with hypoxia alone: 23.4 versus
      35.0 cells/high-power field (p = 0.01), with no change in other markers of
      inhibitory or excitatory neurons. Despite abnormal inhibitory neuron phenotype,
      spontaneous activity of single units and development of orientation selective
      responses were intact following neonatal HI, while overall visual responses were
      reduced. Our data suggest that specific plasticity mechanisms are impaired
      following early brain injury and that the impairment is associated with altered
      inhibitory neuronal development and cortical activation.

PMID- 20053891
TI  - Death-associated protein kinase-mediated cell death modulated by interaction with
      DANGER.
AB  - Death-associated protein kinase (DAPK) is a key player in multiple cell death
      signaling pathways. We report that DAPK is regulated by DANGER, a partial MAB-21
      domain-containing protein. DANGER binds directly to DAPK and inhibits DAPK
      catalytic activity. DANGER-deficient mouse embryonic fibroblasts and neurons
      exhibit greater DAPK activity and increased sensitivity to cell death stimuli
      than do wild-type control cells. In addition, DANGER-deficient mice manifest more
      severe brain damage after acute excitotoxicity and transient cerebral ischemia
      than do control mice. Accordingly, DANGER may physiologically regulate the
      viability of neurons and represent a potential therapeutic target for stroke and
      neurodegenerative diseases.

PMID- 20053892
TI  - Selective T-type calcium channel block in thalamic neurons reveals channel
      redundancy and physiological impact of I(T)window.
AB  - Although it is well established that low-voltage-activated T-type Ca(2+) channels
      play a key role in many neurophysiological functions and pathological states, the
      lack of selective and potent antagonists has so far hampered a detailed analysis
      of the full impact these channels might have on single-cell and neuronal network
      excitability as well as on Ca(2+) homeostasis. Recently, a novel series of
      piperidine-based molecules has been shown to selectively block recombinant T-type
      but not high-voltage-activated (HVA) Ca(2+) channels and to affect a number of
      physiological and pathological T-type channel-dependent behaviors. Here we
      directly show that one of these compounds, 3,5-dichloro-N-[1-(2,2-dimethyl
      tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2),
      exerts a specific, potent (IC(50) = 22 nm), and reversible inhibition of T-type
      Ca(2+) currents of thalamocortical and reticular thalamic neurons, without any
      action on HVA Ca(2+) currents, Na(+) currents, action potentials, and
      glutamatergic and GABAergic synaptic currents. Thus, under current-clamp
      conditions, the low-threshold Ca(2+) potential (LTCP)-dependent high-frequency
      burst firing of thalamic neurons is abolished by TTA-P2, whereas tonic firing
      remains unaltered. Using TTA-P2, we provide the first direct demonstration of the
      presence of a window component of Ca(2+) channels in neurons and its contribution
      to the resting membrane potential of thalamic neurons and to the Up state of
      their intrinsically generated slow (<1 Hz) oscillation. Moreover, we demonstrate
      that activation of only a small fraction of the T-type channel population is
      required to generate robust LTCPs, suggesting that LTCP-driven bursts of action
      potentials can be evoked at depolarized potentials where the vast majority of T
      type channels are inactivated.

PMID- 20053893
TI  - Recruitment of early postnatal parvalbumin-positive hippocampal interneurons by
      GABAergic excitation.
AB  - GABAergic synaptic inputs targeting cortical principal cells undergo marked
      changes in their functional properties from depolarizing at early postnatal life
      to hyperpolarizing at mature stages. In contrast, the nature of GABA(A) receptor
      mediated signaling in interneurons during maturation of neuronal networks is
      controversial. By using gramicidin perforated-patch and whole-cell recordings
      from LIM homeobox 6 (Lhx6)-positive dentate gyrus perisomatic-targeting
      parvalbumin-expressing interneurons (PV-INs), we show that signaling at first
      formed GABAergic synapses at postnatal day 3 (P3) is excitatory and switches to
      shunting during the course of the first to second postnatal week. GABAergic
      synaptic inputs at P3-P6 reliably evoke action potentials in 65% of Lhx6-EGFP
      expressing perisomatic-targeting cells and boost spike induction upon conjoint
      activation of glutamatergic fibers. Thus, GABAergic inputs change their
      functional role during maturation. They facilitate the recruitment of perisomatic
      targeting INs in early postnatal circuits when network connectivity and synaptic
      glutamate receptor-mediated excitation are low and control spike timing at later
      stages when connectivity and glutamate-mediated drive are high.

PMID- 20053894
TI  - Amygdala neural encoding of the absence of reward during extinction.
AB  - The basolateral amygdala complex (BLA) has been identified as a critical
      structure mediating fear extinction. However, little is known about the
      functional role of neurons in the BLA during the extinction of a reward-seeking
      behavior. Here, we used in vivo electrophysiology procedures in freely moving
      rats to investigate whether and how the BLA encodes the extinction of responding
      for sucrose. We recorded 330 neurons from 15 rats during a within-session
      extinction procedure following training under a partial reinforcement schedule.
      Several distinct populations of neurons change their response profiles as the rat
      ceases to respond for the omitted reinforcer. One population of neurons (32 of
      330; 10%), which responded selectively to port entries in the presence, but not
      the absence, of sucrose during maintenance, subsequently developed a phasic
      response to port entries in the absence of sucrose during the extinction epoch
      only. The relative proportion of these "reinforcement-omission" neurons per rat
      was correlated with response intensity during extinction, as well as with the
      rate at which reward-seeking behavior was extinguished. A subpopulation of
      neurons responded with opposite phasic changes in activity to port entries in the
      presence of sucrose and to port entries during extinction, demonstrating that BLA
      neurons may contribute to the detection of value differences between expected and
      actual outcomes. Another population of neurons (47 of 330; 14%) responded to the
      empty port only during extinction. Because BLA neural correlates reflect the
      omission of an expected reward, these neuronal populations may contribute to the
      expression of behavior during extinction.

PMID- 20053895
TI  - Trans-splicing-mediated improvement in a severe mouse model of spinal muscular
      atrophy.
AB  - Spinal muscular atrophy is a leading genetic cause of infantile death and occurs
      in approximately 1/6000 live births. SMA is caused by the loss of Survival Motor
      Neuron-1 (SMN1), however, all patients retain at least one copy of a nearly
      identical gene called SMN2. While SMN2 and SMN1 are comprised of identical coding
      sequences, the majority of SMN2 transcripts are alternatively spliced, encoding a
      truncated protein that is unstable and nonfunctional. Considerable effort has
      focused upon modulating the SMN2 alternative splicing event since this would
      produce more wild-type protein. Recently we reported the development of an
      optimized trans-splicing system that involved the coexpression of a SMN2 trans
      splicing RNA and an antisense RNA that blocks a downstream splice site in SMN2
      pre-mRNA. Here, we demonstrate that in vivo delivery of the optimized trans
      splicing vector increases an important SMN-dependent activity, snRNP assembly, in
      disease-relevant tissue in the SMA mouse model. A single injection of the vector
      into the intracerebral-ventricular space in SMA neonates also lessens the
      severity of the SMA phenotype in a severe SMA mouse model, extending survival
      approximately 70%. Collectively, these results provide the first in vivo
      demonstration that SMN2 trans-splicing leads to a lessening of the severity of
      the SMA phenotype and provide evidence for the power of this strategy for
      reprogramming genetic diseases at the pre-mRNA level.

PMID- 20053896
TI  - Distinct mechanisms produce functionally complementary actions of neuropeptides
      that are structurally related but derived from different precursors.
AB  - Many bioactive neuropeptides containing RFamide at their C terminus have been
      described in both invertebrates and vertebrates. To obtain insight into the
      functional logic of RFamide signaling, we investigate it here in the feeding
      system of Aplysia. We focus on the expression, localization, and actions of two
      families of RFamide peptides, the FRFamides and FMRFamide, in the central
      neuronal circuitry and the peripheral musculature that generate the feeding
      movements. We describe the cloning of the FRFamide precursor protein and show
      that the FRFamides and FMRFamide are derived from different precursors. We map
      the expression of the FRFamide and FMRFamide precursors in the feeding circuitry
      using in situ hybridization and immunostaining and confirm proteolytic processing
      of the FRFamide precursor by mass spectrometry. We show that the two precursors
      are expressed in different populations of sensory neurons in the feeding system.
      In a representative feeding muscle, we demonstrate the presence of both FRFamides
      and FMRFamide and their release, probably from the processes of the sensory
      neurons in the muscle. Both centrally and in the periphery, the FRFamides and
      FMRFamide act in distinct ways, apparently through distinct mechanisms, and
      nevertheless, from an overall functional perspective, their actions are
      complementary. Together, the FRFamides and FMRFamide convert feeding motor
      programs from ingestive to egestive and depress feeding muscle contractions. We
      conclude that these structurally related peptides, although derived from
      different precursors, expressed in different neurons, and acting through
      different mechanisms, remain related to each other in the functional roles that
      they play in the system.

PMID- 20053897
TI  - Mechanisms of spatial attention control in frontal and parietal cortex.
AB  - Theories of spatial attentional control have been largely based upon studies of
      patients suffering from visuospatial neglect, resulting from circumscribed
      lesions of frontal and posterior parietal cortex. In the intact brain, the
      control of spatial attention has been related to a distributed frontoparietal
      attention network. Little is known about the nature of the control mechanisms
      exerted by this network. Here, we used a novel region-of-interest approach to
      relate activations of the attention network to recently described topographic
      areas in frontal cortex [frontal eye field (FEF), PreCC/IFS (precentral
      cortex/inferior frontal sulcus)] and parietal cortex [intraparietal sulcus areas
      (IPS1-IPS5) and an area in the superior parietal lobule (SPL1)] to examine their
      spatial attention signals. We found that attention signals in most topographic
      areas were spatially specific, with stronger responses when attention was
      directed to the contralateral than to the ipsilateral visual field. Importantly,
      two hemispheric asymmetries were found. First, a region in only right, but not
      left SPL1 carried spatial attention signals. Second, left FEF and left posterior
      parietal cortex (IPS1/2) generated stronger contralateral biasing signals than
      their counterparts in the right hemisphere. These findings are the first to
      characterize spatial attention signals in topographic frontal and parietal cortex
      and provide a neural basis in support of an interhemispheric competition account
      of spatial attentional control.

PMID- 20053898
TI  - Competition in visual cortex impedes attention to multiple items.
AB  - Traditional explanations of our limited attentional capacity focus on our ability
      to direct attention to multiple items. We ask whether this difficulty in
      simultaneously attending to multiple items stems from an inability to effectively
      represent multiple attended items. Although attending to one of a set of
      neighboring stimuli can isolate it from competitive interactions in visual
      cortex, no such isolation should occur if multiple competing items are attended.
      Indeed, we find that attention is ineffective at enhancing blood oxygen level
      dependent signal in visual cortical area V4 when it is directed to three stimuli
      simultaneously, but only when those three stimuli compete in visual cortex. This
      suggests that competition may prevent attention from acting as effectively on
      representations of multiple items as it does on representations of a single item.
      In contrast to traditional explanations that posit limits in the sources of
      attentional control, we show that mechanisms at the sites of stimulus
      representation may also impose limits on our ability to attend to multiple items
      simultaneously.

PMID- 20053900
TI  - Norrin promotes vascular regrowth after oxygen-induced retinal vessel loss and
      suppresses retinopathy in mice.
AB  - Norrin is a secreted protein that is involved in retinal angiogenesis and
      activates the Wnt-signaling pathway. We studied the role of Norrin in
      microvascular endothelial cells in vitro, and in a mouse model of retinopathy
      characterized by oxygen-induced vascular loss followed by hypoxia-induced
      pathological neovascularization. Recombinant Norrin significantly increased
      proliferation, viability, migration, and tube formation in vitro. Two independent
      transgenic mouse strains with ectopic overexpression of Norrin from the lens
      (betaB1-Crystallin-Norrin), or the retinal pigment epithelium (Rpe65-Norrin) were
      generated and exposed to high oxygen. Following oxygen treatment, vascular loss
      was significantly smaller in retinae of transgenic mice from both strains as
      compared to wild-type littermates. In addition, the anatomical correct regrowth
      of vessels was significantly increased, while pathological neovascularization was
      suppressed. In vitro and in vivo effects of Norrin could be blocked by adding DKK
      (Dickkopf)-1, an inhibitor of Wnt/beta-catenin signaling. Treatment of
      microvascular endothelial cells with Norrin caused a substantial increase in the
      expression of angiopoietin-2 (Ang-2). When inhibitory antibodies against Ang-2
      were added to Norrin, the proliferative effects of Norrin were significantly
      suppressed. We conclude that Norrin is a potent factor to induce angiogenesis in
      microvascular endothelial cells, which has the distinct potential to suppress the
      damaging effects of oxygen-induced retinopathy in vivo. The effects of Norrin
      appear to be mediated, at least partially, via the induction of Ang-2.

PMID- 20053899
TI  - Electrophysiological characterization of V2a interneurons and their locomotor
      related activity in the neonatal mouse spinal cord.
AB  - The V2a class of Chx10-expressing interneurons has been implicated in frequency
      dependent control of left-right phase during locomotion in the mouse. We have
      used the Chx10::CFP mouse line to further investigate the properties and
      locomotion-related activity of V2a interneurons in the isolated neonatal spinal
      cord. V2a interneurons can be divided into three classes, based on their tonic,
      phasic, or delayed-onset responses to step depolarization. Electrical coupling is
      found only between neurons of same class and helps to synchronize neuronal
      activity within the class. Serotonin (5-HT) excites isolated tonic V2a
      interneurons by depolarizing the neurons and increasing their membrane input
      resistance, with no significant effects on action potential properties, a
      mechanism distinct from 5-HT excitation of commissural interneurons. During NMDA
      /5-HT-induced locomotor-like activity, patch-clamp recordings and two-photon
      calcium imaging experiments show that approximately half of V2a interneurons fire
      rhythmically with ventral root-recorded motor activity; the rhythmic V2a
      interneurons fired during one half of the cycle, in phase with either the
      ipsilateral or the contralateral L2 ventral root bursts. The percentage of
      rhythmically firing V2a interneurons increases during higher-frequency fictive
      locomotion, and they become significantly more rhythmic in their firing during
      the locomotor cycle; this may help to explain the frequency-dependent shift in
      left-right coupling in Chx10::DTA mice, which lack these neurons. Our results
      together with data from the accompanying paper (Dougherty and Kiehn, 2009)
      reinforce earlier proposals that the V2a interneurons are components of the
      hindlimb central pattern generator, helping to organize left-right locomotor
      coordination in the neonatal mouse spinal cord.

PMID- 20053901
TI  - Pinna cues determine orienting response modes to synchronous sounds in elevation.
AB  - To program a goal-directed orienting response toward a sound source embedded in
      an acoustic scene, the audiomotor system should detect and select the target
      against a background. Here, we focus on whether the system can segregate
      synchronous sounds in the midsagittal plane (elevation), a task requiring the
      auditory system to dissociate the pinna-induced spectral localization cues. Human
      listeners made rapid head-orienting responses toward either a single sound source
      (broadband buzzer or Gaussian noise) or toward two simultaneously presented
      sounds (buzzer and noise) at a wide variety of locations in the midsagittal
      plane. In the latter case, listeners had to orient to the buzzer (target) and
      ignore the noise (nontarget). In the single-sound condition, localization was
      accurate. However, in the double-sound condition, response endpoints depended on
      relative sound level and spatial disparity. The loudest sound dominated the
      responses, regardless of whether it was the target or the nontarget. When the
      sounds had about equal intensities and their spatial disparity was sufficiently
      small, endpoint distributions were well described by weighted averaging. However,
      when spatial disparities exceeded approximately 45 degrees, response endpoint
      distributions became bimodal. Similar response behavior has been reported for
      visuomotor experiments, for which averaging and bimodal endpoint distributions
      are thought to arise from neural interactions within retinotopically organized
      visuomotor maps. We show, however, that the auditory-evoked responses can be well
      explained by the idiosyncratic acoustics of the pinnae. Hence basic principles of
      target representation and selection for audition and vision appear to differ
      profoundly.

PMID- 20053902
TI  - Implicit visuomotor processing for quick online reactions is robust against
      aging.
AB  - It is well established that humans can react more quickly to a visual stimulus in
      the visual field center than to one in the visual periphery and that the reaction
      to a stimulus in the visual periphery markedly deteriorates with aging. These
      tendencies are true in conventional discrimination-reaction tasks. Surprisingly,
      however, we found that they are entirely different when reactions are induced by
      the same visual stimuli during reaching movements. The reaction time for a
      stimulus in the visual periphery was significantly faster than in the central
      vision, and age-related slowing of reactions to the stimulus in the visual
      periphery were quite small, compared to that observed in the conventional
      reaction tasks. This inconsistent slowing of reactions in different motor
      conditions underscores a distinctive visuomotor pathway for online control, which
      is more robust against age-related deterioration.

PMID- 20053903
TI  - Drug-induced plasticity contributing to heightened relapse susceptibility:
      neurochemical changes and augmented reinstatement in high-intake rats.
AB  - A key in understanding the neurobiology of addiction and developing effective
      pharmacotherapies is revealing drug-induced plasticity that results in heightened
      relapse susceptibility. Previous studies have demonstrated that increased
      extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc)
      is necessary for cocaine-induced reinstatement. In this report, we examined
      whether drug-induced adaptations that are necessary to generate cocaine-induced
      reinstatement also determine relapse vulnerability. To do this, rats were
      assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5
      mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug
      intake since these manipulations produce groups of rats exhibiting differences in
      the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last
      session, cocaine-induced drug seeking and extracellular levels of glutamate and
      dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats
      exhibited a more robust cocaine-induced increase in extracellular levels of
      dopamine but not glutamate. Further, increased reinstatement in high-intake rats
      was no longer observed when the D(1) receptor antagonist SCH-23390 was infused
      into the NAcc. The sensitized dopamine response to cocaine in high-intake rats
      may involve blunted cystine-glutamate exchange by system x(c(-)). Reduced (14)C
      cystine uptake through system x(c(-)) was evident in NAcc tissue slices obtained
      from high-intake rats, and the augmented dopamine response in these rats was no
      longer observed when subjects received the cysteine prodrug N-acetyl cysteine.
      These data reveal a role for drug-induced NAcc dopamine in heightened relapse
      vulnerability observed in rats with a history of high levels of drug intake.

PMID- 20053904
TI  - Glutamatergic and nonglutamatergic neurons of the ventral tegmental area
      establish local synaptic contacts with dopaminergic and nondopaminergic neurons.
AB  - The ventral tegmental area (VTA) contributes to reward and motivation signaling.
      In addition to the well established populations of dopamine (DA) or GABA VTA
      neurons, glutamatergic neurons were recently discovered in the VTA. These
      glutamatergic neurons express the vesicular glutamate transporter 2, VGluT2. To
      investigate whether VTA glutamatergic neurons establish local synapses, we tagged
      axon terminals from resident VTA neurons by intra-VTA injection of Phaseolus
      vulgaris leucoagglutinin (PHA-L) or an adeno-associated virus encoding wheat germ
      agglutinin (WGA) and by immunoelectron microscopy determined the presence of
      VGluT2 in PHA-L- or WGA-positive terminals. We found that PHA-L- or WGA-positive
      terminals from tagged VTA cells made asymmetric or symmetric synapses within the
      VTA. VGluT2 immunoreactivity was detected in the vast majority of PHA-L- or WGA
      positive terminals forming asymmetric synapses. These results indicate that both
      VTA glutamatergic and nonglutamatergic (likely GABAergic) neurons establish local
      synapses. To examine the possible DAergic nature of postsynaptic targets of VTA
      glutamatergic neurons, we did triple immunolabeling with antibodies against
      VGluT2, tyrosine hydroxylase (TH), and PHA-L. From triple-labeled tissue, we
      found that double-labeled PHA-L (+)/VGluT2 (+) axon terminals formed synaptic
      contacts on dendrites of both TH-positive and TH-negative cells. Consistent with
      these anatomical observations, in whole-cell slice recordings of VTA neurons we
      observed that blocking action potential activity significantly decreased the
      frequency of synaptic glutamatergic events in DAergic and non-DAergic neurons.
      These observations indicate that resident VTA glutamatergic neurons are likely to
      affect both DAergic and non-DAergic neurotransmission arising from the VTA.

PMID- 20053905
TI  - Gain control in CA1 pyramidal cells using changes in somatic conductance.
AB  - Gain modulation is an important feature of neural activity. Previous work has
      focused on the ability of background synaptic noise to modulate the slope (i.e.,
      gain) of the frequency-current (f-I) relationship in neurons. To date,
      demonstrations of gain control that are independent of synaptic noise have been
      limited. We investigated the effects of increasing somatic conductance in the
      form of tonic inhibition on the initial and steady-state f-I relationship of CA1
      pyramidal cells. We find that increasing membrane conductance reduces the gain of
      the steady-state f-I relationship through a graded increase in the magnitude of
      spike frequency adaptation. Increased adaptation arises through a conductance
      induced depolarization of spike voltage threshold. Thus, by increasing the
      magnitude of spike frequency adaptation, added conductance can reduce the gain of
      the steady-state f-I relationship in the absence of random background membrane
      fluctuations.

PMID- 20053906
TI  - SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor
      trafficking.
AB  - Protein kinase C (PKC) enhances NMDA receptor (NMDAR)-mediated currents and
      promotes NMDAR delivery to the cell surface via SNARE-dependent exocytosis.
      Although the mechanisms of PKC potentiation are established, the molecular target
      of PKC is unclear. Here we show that synaptosomal-associated protein of 25 kDa
      (SNAP-25), a SNARE protein, is functionally relevant to PKC-dependent NMDAR
      insertion, and identify serine residue-187 as the molecular target of PKC
      phosphorylation. Constitutively active PKC delivered via the patch pipette
      potentiated NMDA (but not AMPA) whole-cell currents in hippocampal neurons.
      Expression of RNAi targeting SNAP-25 or mutant SNAP-25(S187A) and/or acute
      disruption of the SNARE complex by treatment with BoNT A, BoNT B or SNAP-25 C
      terminal blocking peptide abolished NMDAR potentiation. A SNAP-25 peptide and
      function-blocking antibody suppressed PKC potentiation of NMDA EPSCs at mossy
      fiber-CA3 synapses. These findings identify SNAP-25 as the target of PKC
      phosphorylation critical to PKC-dependent incorporation of synaptic NMDARs and
      document a postsynaptic action of this major SNARE protein relevant to synaptic
      plasticity.

PMID- 20053908
TI  - Segregation of ipsilateral retinal ganglion cell axons at the optic chiasm
      requires the Shh receptor Boc.
AB  - The pattern of contralaterally and ipsilaterally projecting retinal ganglion cell
      (RGC) axons at the optic chiasm is essential for the establishment of binocular
      vision. Contralateral axons cross the chiasm midline as they progress from the
      optic nerve to the optic tract. In contrast, ipsilateral axons deviate from the
      chiasm and continue in the ipsilateral optic tract, avoiding the chiasm midline.
      The molecular mechanism underlying this phenomenon is not completely understood.
      Here we show that the Sonic Hedgehog (Shh) receptor Boc is enriched in
      ipsilateral RGCs of the developing retina. Together with the presence of Shh at
      the midline, this complementary expression pattern led us to hypothesize that Shh
      might repel ipsilateral RGC axons at the chiasm. Consistent with this hypothesis,
      we found that only Boc-positive RGC axons retract in vitro in response to Shh and
      that this response is lost in Boc mutant RGCs. In vivo, we show that Boc is
      required for the normal segregation of ipsilateral axons at the optic chiasm and,
      conversely, that Boc expression in contralateral RGCs prevents their axons from
      crossing the optic chiasm. Together, these results suggest that Shh repels
      ipsilateral RGC axons at the optic chiasm via its receptor Boc. This work
      identifies a novel molecular pathway required for the segregation of axons at the
      optic chiasm.

PMID- 20053907
TI  - Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons
      during macrophage-induced axonal dieback after spinal cord injury.
AB  - We previously demonstrated that activated ED1+ macrophages induce extensive
      axonal dieback of dystrophic sensory axons in vivo and in vitro. Interestingly,
      after spinal cord injury, the regenerating front of axons is typically found in
      areas rich in ED1+ cells, but devoid of reactive astrocyte processes. These
      observations suggested that another cell type must be present in these areas to
      counteract deleterious effects of macrophages. Cells expressing the purportedly
      inhibitory chondroitin sulfate proteoglycan NG2 proliferate in the lesion and
      intermingle with macrophages, but their influence on regeneration is highly
      controversial. Our in vivo analysis of dorsal column crush lesions confirms the
      close association between NG2+ cells and injured axons. We hypothesized that NG2+
      cells were growth promoting and thereby served to increase axonal stability
      following spinal cord injury. We observed that the interactions between
      dystrophic adult sensory neurons and primary NG2+ cells derived from the adult
      spinal cord can indeed stabilize the dystrophic growth cone during macrophage
      attack. NG2+ cells expressed high levels of laminin and fibronectin, which
      promote neurite outgrowth on the surface of these cells. Our data also
      demonstrate that NG2+ cells, but not astrocytes, use matrix metalloproteases to
      extend across a region of inhibitory proteoglycan, and provide a permissive
      bridge for adult sensory axons. These data support the hypothesis that NG2+ cells
      are not inhibitory to regenerating sensory axons and, in fact, they may provide a
      favorable substrate that can stabilize the regenerating front of dystrophic axons
      in the inhibitory environment of the glial scar.

PMID- 20053909
TI  - Progressive and lasting amplification of accumbal nicotine-seeking neural
      signals.
AB  - Although neuroadaptations in the nucleus accumbens (NAc) are thought to
      contribute to nicotine addiction, little is known about the chronic effects of
      nicotine on NAc neuronal activity. In the present experiment, rats were exposed
      to a 23 d period of nicotine self-administration (SA), a 30 d abstinence period,
      and a 7 d period of reexposure to SA. Chronic electrophysiological procedures
      were used to record the activity of individual NAc neurons on the 3rd and 23rd
      days of initial SA and on the 1st, 3rd, and 7th days of reexposure. Between
      session comparisons showed that NAc neurons exhibit two patterns of plasticity
      under the present experimental conditions. First, phasic-increase firing patterns
      time-locked to the nicotine-reinforced lever press do not change during initial
      SA, but then show increases in prevalence and amplitude after abstinence, which
      persist during reexposure. Second, for neurons that show no phasic response time
      locked to the nicotine-reinforced lever press, average baseline and SA firing
      rates decrease during initial SA, return to normal during abstinence, and
      decrease again during reexposure. As a combined consequence of the two types of
      neurophysiological plasticity, average firing rate of NAc neurons at the time of
      nicotine-directed behavior undergoes a progressive and persistent net
      amplification, across the successive stages of SA, abstinence, and reexposure.
      This net increase in NAc firing at the time of nicotine-directed behavior occurs
      in association with an increase in animals' motivation to seek nicotine. The
      adaptations that occur in nicotine-exposed animals do not occur in animals
      exposed to sucrose. The NAc neurophysiological plasticity potentially contributes
      to compulsive tobacco use.

PMID- 20053910
TI  - Licking-induced synchrony in the taste-reward circuit improves cue discrimination
      during learning.
AB  - Animals learn which foods to ingest and which to avoid. Despite many studies, the
      electrophysiological correlates underlying this behavior at the gustatory-reward
      circuit level remain poorly understood. For this reason, we measured the
      simultaneous electrical activity of neuronal ensembles in the orbitofrontal
      cortex, insular cortex, amygdala, and nucleus accumbens while rats licked for
      taste cues and learned to perform a taste discrimination go/no-go task. This
      study revealed that rhythmic licking entrains the activity in all these brain
      regions, suggesting that the animal's licking acts as an "internal clock signal"
      against which single spikes can be synchronized. That is, as animals learned a
      go/no-go task, there were increases in the number of licking coherent neurons as
      well as synchronous spiking between neuron pairs from different brain regions.
      Moreover, a subpopulation of gustatory cue-selective neurons that fired in
      synchrony with licking exhibited a greater ability to discriminate among tastants
      than nonsynchronized neurons. This effect was seen in all four recorded areas and
      increased markedly after learning, particularly after the cue was delivered and
      before the animals made a movement to obtain an appetitive or aversive tastant.
      Overall, these results show that, throughout a large segment of the taste-reward
      circuit, appetitive and aversive associative learning improves spike-timing
      precision, suggesting that proficiency in solving a taste discrimination go/no-go
      task requires licking-induced neural ensemble synchronous activity.

PMID- 20053912
TI  - Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a
      mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder
      caused by a polyglutamine expansion in the huntingtin protein (Htt). Group I
      metabotropic glutamate receptors (mGluRs) are coupled to G(alphaq) and play an
      important role in neuronal survival. We have previously demonstrated that mGluRs
      interact with Htt. Here we used striatal neuronal primary cultures and acute
      striatal slices to demonstrate that mGluR-mediated signaling pathways are altered
      in a presymptomatic mouse model of HD (Hdh(Q111/Q111)), as compared to those of
      control mice (Hdh(Q20/Q20)). mGluR1/5-mediated inositol phosphate (InsP)
      formation is desensitized in striatal slices from Hdh(Q111/Q111) mice and this
      desensitization is PKC-mediated. Despite of decreased InsP formation, (S)-3,5
      dihydroxylphenylglycine (DHPG)-mediated Ca(2+) release is higher in
      Hdh(Q111/Q111) than in Hdh(Q20/Q20) neurons. Furthermore, mGluR1/5-stimulated AKT
      and extracellular signal-regulated kinase (ERK) activation is altered in
      Hdh(Q111/Q111) mice. Basal AKT activation is higher in Hdh(Q111/Q111) neurons and
      this increase is mGluR5 dependent. Moreover, mGluR5 activation leads to higher
      levels of ERK activation in Hdh(Q111/Q111) than in Hdh(Q20/Q20) striatum. PKC
      inhibition not only brings Hdh(Q111/Q111) DHPG-stimulated InsP formation to
      Hdh(Q20/Q20) levels, but also causes an increase in neuronal cell death in
      Hdh(Q111/Q111) neurons. However, PKC inhibition does not modify neuronal cell
      death in Hdh(Q20/Q20) neurons, suggesting that PKC-mediated desensitization of
      mGluR1/5 in Hdh(Q111/Q111) mice might be protective in HD. Together, these data
      indicate that group I mGluR-mediated signaling pathways are altered in HD and
      that these cell signaling adaptations could be important for striatal neurons
      survival.

PMID- 20053911
TI  - Reduction of adult hippocampal neurogenesis confers vulnerability in an animal
      model of cocaine addiction.
AB  - Drugs of abuse dynamically regulate adult neurogenesis, which appears important
      for some types of learning and memory. Interestingly, a major site of adult
      neurogenesis, the hippocampus, is important in the formation of drug-context
      associations and in the mediation of drug-taking and drug-seeking behaviors in
      animal models of addiction. Correlative evidence suggests an inverse relationship
      between hippocampal neurogenesis and drug-taking or drug-seeking behaviors, but
      the lack of a causative link has made the relationship between adult-generated
      neurons and addiction unclear. We used rat intravenous cocaine self
      administration in rodents, a clinically relevant animal model of addiction, to
      test the hypothesis that suppression of adult hippocampal neurogenesis enhances
      vulnerability to addiction and relapse. Suppression of adult hippocampal
      neurogenesis via cranial irradiation before drug-taking significantly increased
      cocaine self-administration on both fixed-ratio and progressive-ratio schedules,
      as well as induced a vertical shift in the dose-response curve. This was not a
      general enhancement of learning, motivation, or locomotion, because sucrose self
      administration and locomotor activity were unchanged in irradiated rats.
      Suppression of adult hippocampal neurogenesis after drug-taking significantly
      enhanced resistance to extinction of drug-seeking behavior. These studies
      identify reduced adult hippocampal neurogenesis as a novel risk factor for
      addiction-related behaviors in an animal model of cocaine addiction. Furthermore,
      they suggest that therapeutics to specifically increase or stabilize adult
      hippocampal neurogenesis could aid in preventing initial addiction as well as
      future relapse.

PMID- 20053913
TI  - Multiscale pattern analysis of orientation-selective activity in the primary
      visual cortex.
AB  - Although orientation columns are less than a millimeter in width, recent
      neuroimaging studies indicate that viewed orientations can be decoded from
      cortical activity patterns sampled at relatively coarse resolutions of several
      millimeters. One proposal is that these differential signals arise from random
      spatial irregularities in the columnar map. However, direct support for this
      hypothesis has yet to be obtained. Here, we used high-field, high-resolution
      functional magnetic resonance imaging (fMRI) and multivariate pattern analysis to
      determine the spatial scales at which orientation-selective information can be
      found in the primary visual cortex (V1) of cats and humans. We applied a
      multiscale pattern analysis approach in which fine- and coarse-scale signals were
      first removed by ideal spatial lowpass and highpass filters, and the residual
      activity patterns then analyzed by linear classifiers. Cat visual cortex, imaged
      at 0.3125 mm resolution, showed a strong orientation signal at the scale of
      individual columns. Nonetheless, reliable orientation bias could still be found
      at spatial scales of several millimeters. In the human visual cortex, imaged at 1
      mm resolution, a majority of orientation information was found on scales of
      millimeters, with small contributions from global spatial biases exceeding
      approximately 1 cm. Our high-resolution imaging results demonstrate a reliable
      millimeters-scale orientation signal, likely emerging from irregular spatial
      arrangements of orientation columns and their supporting vasculature. fMRI
      pattern analysis methods are thus likely to be sensitive to signals originating
      from other irregular columnar structures elsewhere in the brain.

PMID- 20053915
TI  - The dorsomedial pathway is not just for reaching: grasping neurons in the medial
      parieto-occipital cortex of the macaque monkey.
AB  - Brain control of prehension is thought to rely on two specific brain circuits: a
      dorsomedial one (involving the areas of the superior parietal lobule and the
      dorsal premotor cortex) involved in the transport of the hand toward the object
      and a dorsolateral one (involving the inferior parietal lobule and the ventral
      premotor cortex) dealing with the preshaping of the hand according to the
      features of the object. The present study aimed at testing whether a pivotal
      component of the dorsomedial pathway (area V6A) is involved also in hand
      preshaping and grip formation to grasp objects of different shapes. Two macaque
      monkeys were trained to reach and grasp different objects. For each object,
      animals used a different grip: whole-hand prehension, finger prehension, hook
      grip, primitive precision grip, and advanced precision grip. Almost half of 235
      neurons recorded from V6A displayed selectivity for a grip or a group of grips.
      Several experimental controls were used to ensure that neural modulation was
      attributable to grip only. These findings, in concert with previous studies
      demonstrating that V6A neurons are modulated by reach direction and wrist
      orientation, that lesion of V6A evokes reaching and grasping deficits, and that
      dorsal premotor cortex contains both reaching and grasping neurons, indicate that
      the dorsomedial parieto-frontal circuit may play a central role in all phases of
      reach-to-grasp action. Our data suggest new directions for the modeling of
      prehension movements and testable predictions for new brain imaging and
      neuropsychological experiments.

PMID- 20053914
TI  - Normal hearing is required for the emergence of long-lasting inhibitory
      potentiation in cortex.
AB  - Long-term synaptic plasticity is a putative mechanism for learning in adults.
      However, there is little understanding of how synaptic plasticity mechanisms
      develop or whether their maturation depends on experience. Since inhibitory
      synapses are particularly malleable to sensory stimulation, long-lasting
      potentiation of inhibitory synapses was characterized in auditory thalamocortical
      slices. Intracortical high-frequency electrical stimulation led to a 67% increase
      in inhibitory synaptic currents. In the absence of stimulation, inhibitory
      potentiation was induced by a brief exposure to exogenous brain-derived
      neurotrophic factor (BDNF). BDNF exposure occluded any additional potentiation by
      high-frequency afferent stimulation, suggesting that BDNF signaling is sufficient
      to account for inhibitory potentiation. Moreover, inhibitory potentiation was
      reduced significantly by extracellular application of a BDNF scavenger or by
      intracellular blockade of BDNF receptor [tropomyosin-related kinase B (TrkB)]
      signaling. In contrast, glutamatergic or GABAergic antagonists did not prevent
      the induction of inhibitory potentiation. Since BDNF and TrkB expression are
      influenced strongly by activity, we predicted that inhibitory potentiation would
      be diminished by manipulations that decrease central auditory activity, such as
      hearing loss. Two forms of hearing loss were examined: conductive hearing loss in
      which the cochleae are not damaged or sensorineural hearing loss in which both
      cochleae are removed. Both forms of hearing loss were found to reduce
      significantly the magnitude of inhibitory potentiation. These data indicate that
      early experience is necessary for the normal development of BDNF-mediated long
      lasting inhibitory potentiation, which may be associated with perceptual deficits
      at later ages.

PMID- 20053916
TI  - Functional, but not anatomical, separation of "what" and "when" in prefrontal
      cortex.
AB  - How does the brain store information over a short period of time? Typically, the
      short-term memory of items or values is thought to be stored in the persistent
      activity of neurons in higher cortical areas. However, the activity of these
      neurons often varies strongly in time, even if time is unimportant for whether or
      not rewards are received. To elucidate this interaction of time and memory, we
      reexamined the activity of neurons in the prefrontal cortex of monkeys performing
      a working memory task. As often observed in higher cortical areas, different
      neurons have highly heterogeneous patterns of activity, making interpretation of
      the data difficult. To overcome these problems, we developed a method that finds
      a new representation of the data in which heterogeneity is much reduced, and time
      and memory-related activities became separate and easily interpretable. This new
      representation consists of a few fundamental activity components that capture 95%
      of the firing rate variance of >800 neurons. Surprisingly, the memory-related
      activity components account for <20% of this firing rate variance. The observed
      heterogeneity of neural responses results from random combinations of these
      fundamental components. Based on these components, we constructed a generative
      linear model of the network activity. The model suggests that the representations
      of time and memory are maintained by separate mechanisms, even while sharing a
      common anatomical substrate. Testable predictions of this hypothesis are
      proposed. We suggest that our method may be applied to data from other tasks in
      which neural responses are highly heterogeneous across neurons, and dependent on
      more than one variable.

PMID- 20053917
TI  - Reducing intracortical inhibition in the adult visual cortex promotes ocular
      dominance plasticity.
AB  - Experience-dependent plasticity in the cortex is often higher during short
      critical periods in postnatal development. The mechanisms limiting adult cortical
      plasticity are still unclear. Maturation of intracortical GABAergic inhibition is
      suggested to be crucial for the closure of the critical period for ocular
      dominance (OD) plasticity in the visual cortex. We find that reduction of
      GABAergic transmission in the adult rat visual cortex partially reactivates OD
      plasticity in response to monocular deprivation (MD). This is accompanied by an
      enhancement of activity-dependent potentiation of synaptic efficacy but not of
      activity-dependent depression. We also found a decrease in the expression of
      chondroitin sulfate proteoglycans in the visual cortex of MD animals with reduced
      inhibition, after the reactivation of OD plasticity. Thus, intracortical
      inhibition is a crucial limiting factor for the induction of experience-dependent
      plasticity in the adult visual cortex.

PMID- 20053918
TI  - Many neuronal and behavioral impairments in transgenic mouse models of
      Alzheimer's disease are independent of caspase cleavage of the amyloid precursor
      protein.
AB  - Previous studies suggested that cleavage of the amyloid precursor protein (APP)
      at aspartate residue 664 by caspases may play a key role in the pathogenesis of
      Alzheimer's disease. Mutation of this site (D664A) prevents caspase cleavage and
      the generation of the C-terminal APP fragments C31 and Jcasp, which have been
      proposed to mediate amyloid-beta (Abeta) neurotoxicity. Here we compared human
      APP transgenic mice with (B254) and without (J20) the D664A mutation in a battery
      of tests. Before Abeta deposition, hAPP-B254 and hAPP-J20 mice had comparable
      hippocampal levels of Abeta(1-42). At 2-3 or 5-7 months of age, hAPP-B254 and
      hAPP-J20 mice had similar abnormalities relative to nontransgenic mice in spatial
      and nonspatial learning and memory, elevated plus maze performance,
      electrophysiological measures of synaptic transmission and plasticity, and levels
      of synaptic activity-related proteins. Thus, caspase cleavage of APP at position
      D664 and generation of C31 do not play a critical role in the development of
      these abnormalities.

PMID- 20053919
TI  - Wild-type cone photoreceptors persist despite neighboring mutant cone
      degeneration.
AB  - In many retinal diseases, the malfunction that results in photoreceptor loss
      occurs only in either rods or cones, but degeneration can progress from the
      affected cell type to its healthy neighbors. Specifically, in human and mouse
      models of Retinitis Pigmentosa the loss of rods results in the death of
      neighboring healthy cones. Significantly less is known about cone-initiated
      degenerations and their affect on neighboring cells. Sometimes rods remain normal
      after cone death, whereas other patients experience a loss of scotopic vision
      over time. The affect of cone death on neighboring cones is unknown. The
      zebrafish is a cone-rich animal model in which the potential for dying cones to
      kill neighboring healthy cones can be evaluated. We previously reported that the
      zebrafish cone phosphodiesterase mutant (pde6c(w59)) displays a rapid death of
      cones soon after their formation and a subsequent loss of rods in the central
      retina. In this study we examine morphological changes associated with cone death
      in vivo in pde6c(w59) fish. We then use blastulae transplantations to create
      chimeric fish with a photoreceptor layer of mixed wild-type (WT) and pde6c(w59)
      cones. We find that the death of inoperative cones does not cause neighboring WT
      cone loss. The survival of WT cones is independent of transplant size and
      location within the retina. Furthermore, transplanted WT cones persist at least
      several weeks after the initial death of dysfunctional mutant cones. Our results
      suggest a potential for the therapeutic transplantation of healthy cones into an
      environment of damaged cones.

PMID- 20053920
TI  - Glycine release from radial cells modulates the spontaneous activity and its
      propagation during early spinal cord development.
AB  - Rhythmic electrical activity is a hallmark of the developing embryonic CNS and is
      required for proper development in addition to genetic programs. Neurotransmitter
      release contributes to the genesis of this activity. In the mouse spinal cord,
      this rhythmic activity occurs after embryonic day 11.5 (E11.5) as waves spreading
      along the entire cord. At E12.5, blocking glycine receptors alters the
      propagation of the rhythmic activity, but the cellular source of the glycine
      receptor agonist, the release mechanisms, and its function remain obscure. At
      this early stage, the presence of synaptic activity even remains unexplored.
      Using isolated embryonic spinal cord preparations and whole-cell patch-clamp
      recordings of identified motoneurons, we find that the first synaptic activity
      develops at E12.5 and is mainly GABAergic. Using a multiple approach including
      direct measurement of neurotransmitter release (i.e., outside-out sniffer
      technique), we also show that, between E12.5 and E14.5, the main source of
      glycine in the embryonic spinal cord is radial cell progenitors, also known to be
      involved in neuronal migration. We then demonstrate that radial cells can release
      glycine during synaptogenesis. This spontaneous non-neuronal glycine release can
      also be evoked by mechanical stimuli and occurs through volume-sensitive chloride
      channels. Finally, we find that basal glycine release upregulates the propagating
      spontaneous rhythmic activity by depolarizing immature neurons and by increasing
      membrane potential fluctuations. Our data raise the question of a new role of
      radial cells as secretory cells involved in the modulation of the spontaneous
      electrical activity of embryonic neuronal networks.

PMID- 20053921
TI  - Continuous electroencephalographic monitoring with radio-telemetry in a rat model
      of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy.
AB  - The development of acquired epilepsy after a perinatal hypoxic-ischemic (HI)
      insult was investigated in rats. After unilateral carotid ligation with hypoxia
      on postnatal day 7, cortical electroencephalographic and behavioral seizures were
      recorded with continuous radio-telemetry and video. Chronic recordings were
      obtained between 2 and 12 months of age in freely behaving HI-treated and sham
      control rats. The hypotheses were that the acquired epilepsy is directly
      associated with an ischemic infarct (i.e., no lesion, no epilepsy), and the
      resultant epilepsy is temporally progressive. Every HI-treated rat with a
      cerebral infarct developed spontaneous epileptiform discharges and recurrent
      seizures (100%); in contrast, no spontaneous epileptiform discharges or seizures
      were detected with continuous monitoring in the HI-treated rats without infarcts.
      The initial seizures at 2 months generally showed focal onset and were
      nonconvulsive. Subsequent seizures had focal onsets that propagated to the
      homotopic contralateral cortex and were nonconvulsive or partial; later seizures
      often appeared to have bilateral onset and were convulsive. Spontaneous
      epileptiform discharges were initially lateralized to ipsilateral neocortex but
      became bilateral over time. The severity and frequency of the spontaneous
      behavioral and electrographic seizures progressively increased over time. In
      every epileptic rat, seizures occurred in distinct clusters with seizure-free
      periods as long as a few weeks. The progressive increase in seizure frequency
      over time was associated with increases in cluster frequency and seizures within
      each cluster. Thus, prolonged, continuous seizure monitoring directly
      demonstrated that the acquired epilepsy after perinatal HI was progressive with
      seizure clusters and was consistently associated with a cerebral infarct.

PMID- 20053922
TI  - L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction
      with aging.
AB  - With advancing age, peripheral conduit and resistance arteries lose the ability
      to effectively dilate owing to endothelial dysfunction. This vascular senescence
      contributes to increased risk of cardiovascular disease (CVD) with aging. L
      arginine plays a role in numerous physiological processes including nitrogen
      detoxification, immunocompetence, growth hormone (GH) secretion, and insulin
      secretion. Recently, a considerable amount of attention has been placed on the
      ability of this amino acid to affect vascular endothelial function. The purpose
      of this review will be to examine the use of L-arginine as a novel nutritional
      strategy to potentially stave progression of vascular dysfunction with aging and
      CVD. Emphasis will be placed on the ability of L-arginine to modulate the
      vascular inflammatory and systemic hormonal milieu, which in turn may have a
      positive effect on vascular endothelial function.

PMID- 20053923
TI  - Influence of cell background on pharmacological rescue of mutant CFTR.
AB  - Cystic fibrosis (CF) is caused by mutations in the CFTR chloride channel.
      Deletion of phenylalanine 508 (F508del), the most frequent CF mutation, impairs
      the maturation and gating of the CFTR protein. Such defects may be corrected in
      vitro by pharmacological modulators named as correctors and potentiators,
      respectively. We have evaluated a panel of correctors and potentiators derived
      from various sources to assess potency, efficacy, and mechanism of action. For
      this purpose, we have used functional and biochemical assays on two different
      cell expression systems, Fischer rat thyroid (FRT) and A549 cells. The order of
      potency and efficacy of potentiators was similar in the two cell types
      considered, with phenylglycine PG-01 and isoxazole UCCF-152 being the most potent
      and least potent, respectively. Most potentiators were also effective on two
      mutations, G551D and G1349D, that cause a purely gating defect. In contrast,
      corrector effect was strongly affected by cell background, with the extreme case
      of many compounds working in one cell type only. Our findings are in favor of a
      direct action of potentiators on CFTR, possibly at a common binding site. In
      contrast, most correctors seem to work indirectly with various mechanisms of
      action. Combinations of correctors acting at different levels may lead to
      additive F508del-CFTR rescue.

PMID- 20053924
TI  - Mitochondrial matrix K+ flux independent of large-conductance Ca2+-activated K+
      channel opening.
AB  - Large-conductance Ca(2+)-activated K(+) channels (BK(Ca)) in the inner
      mitochondrial membrane may play a role in protecting against cardiac ischemia
      reperfusion injury. NS1619 (30 microM), an activator of BK(Ca) channels, was
      shown to increase respiration and to stimulate reactive oxygen species generation
      in isolated cardiac mitochondria energized with succinate. Here, we tested
      effects of NS1619 to alter matrix K(+), H(+), and swelling in mitochondria
      isolated from guinea pig hearts. We found that 30 microM NS1619 did not change
      matrix K(+), H(+), and swelling, but that 50 and 100 microM NS1619 caused a
      concentration-dependent increase in matrix K(+) influx (PBFI fluorescence) only
      when quinine was present to block K(+)/H(+) exchange (KHE); this was accompanied
      by increased mitochondrial matrix volume (light scattering). Matrix pH (BCECF
      fluorescence) was decreased slightly by 50 and 100 microM NS1619 but markedly
      more so when quinine was present. NS1619 (100 microM) caused a significant leak
      in lipid bilayers, and this was enhanced in the presence of quinine. The K(+)
      ionophore valinomycin (0.25 nM), which like NS1619 increased matrix volume and
      increased K(+) influx in the presence of quinine, caused matrix alkalinization
      followed by acidification when quinine was absent, and only alkalinization when
      quinine was present. If K(+) is exchanged instantly by H(+) through activated
      KHE, then matrix K(+) influx should stimulate H(+) influx through KHE and cause
      matrix acidification. Our results indicate that KHE is not activated immediately
      by NS1619-induced K(+) influx, that NS1619 induces matrix K(+) and H(+) influx
      through a nonspecific transport mechanism, and that enhancement with quinine is
      not due to the blocking of KHE, but to a nonspecific effect of quinine to enhance
      current leak by NS1619.

PMID- 20053925
TI  - Stimulation of neuronal KATP channels by cGMP-dependent protein kinase:
      involvement of ROS and 5-hydroxydecanoate-sensitive factors in signal
      transduction.
AB  - The ATP-sensitive potassium (K(ATP)) channel couples intracellular metabolic
      state to membrane excitability. Recently, we demonstrated that neuronal K(ATP)
      channels are functionally enhanced by activation of a nitric oxide (NO)/cGMP/cGMP
      dependent protein kinase (PKG) signaling cascade. In this study, we further
      investigated the intracellular mechanism underlying PKG stimulation of neuronal
      K(ATP) channels. By performing single-channel recordings in transfected HEK293
      and neuroblastoma SH-SY5Y cells, we found that the increase of Kir6.2/SUR1 (i.e.,
      the neuronal-type K(ATP)) channel currents by PKG activation in cell-attached
      patches was diminished by 5-hydroxydecanoate (5-HD), an inhibitor of the putative
      mitochondrial K(ATP) channel; N-(2-mercaptopropionyl)glycine, a reactive oxygen
      species (ROS) scavenger, and catalase, a hydrogen peroxide (H(2)O(2))-decomposing
      enzyme. These reagents also ablated NO-induced K(ATP) channel stimulation and
      prevented the shifts in the single-channel open- and closed-time distributions
      resulting from PKG activation and NO induction. Bath application of H(2)O(2)
      reproduced PKG stimulation of Kir6.2/SUR1 but did not activate tetrameric
      Kir6.2LRKR368/369/370/371AAAA channels. Moreover, neither the PKG activator nor
      exogenous H(2)O(2) was able to enhance the function of K(ATP) channels in the
      presence of Ca(2+) chelators and calmodulin antagonists, whereas the stimulatory
      effect of H(2)O(2) was unaffected by 5-HD. Altogether, in this report we provide
      novel evidence that activation of PKG stimulates neuronal K(ATP) channels by
      modulating intrinsic channel gating via a 5-HD-sensitive
      factor(s)/ROS/Ca(2+)/calmodulin signaling pathway that requires the presence of
      the SUR1 subunit. This signaling pathway may contribute to neuroprotection
      against ischemic injury and regulation of neuronal excitability and
      neurotransmitter release by modulating the function of neuronal K(ATP) channels.

PMID- 20053926
TI  - Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with
      loss of repressive histone modifications.
AB  - Unlike epigenetic silencing of tumor suppressor genes, the role of epigenetic
      derepression of cancer-promoting genes or oncogenes in carcinogenesis remains
      less well understood. The tight junction proteins claudin-3 and claudin-4 are
      frequently overexpressed in ovarian cancer and their overexpression was
      previously reported to promote the migration and invasion of ovarian epithelial
      cells. Here, we show that the expression of claudin-3 and claudin-4 is repressed
      in ovarian epithelial cells in association with promoter 'bivalent' histone
      modifications, containing both the activating trimethylated histone H3 lysine 4
      (H3K4me3) mark and the repressive mark of trimethylated histone H3 lysine 27
      (H3K27me3). During ovarian tumorigenesis, derepression of CLDN3 and CLDN4
      expression correlates with loss of H3K27me3 in addition to trimethylated histone
      H4 lysine 20 (H4K20me3), another repressive histone modification. Although CLDN4
      repression was accompanied by both DNA hypermethylation and repressive histone
      modifications, DNA methylation was not required for CLDN3 repression in
      immortalized ovarian epithelial cells. Moreover, activation of both CLDN3 and
      CLDN4 in ovarian cancer cells was associated with simultaneous changes in
      multiple histone modifications, whereas H3K27me3 loss alone was insufficient for
      their derepression. CLDN4 repression was robustly reversed by combined treatment
      targeting both DNA demethylation and histone acetylation. Our study strongly
      suggests that in addition to the well-known chromatin-associated silencing of
      tumor suppressor genes, epigenetic derepression by the conversely related loss of
      repressive chromatin modifications also contributes to ovarian tumorigenesis via
      activation of cancer-promoting genes or candidate oncogenes.

PMID- 20053927
TI  - microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network.
AB  - microRNAs (miRNAs) are small non-coding RNAs and have been implicated in the
      pathology of various diseases, including cancer. Here we report that the miRNA
      profiles have been changed after knockdown of one of the most important oncogene
      c-MYC or re-expression of a candidate tumor suppressor gene SPLUNC1 in
      nasopharyngeal carcinoma (NPC) cells. Both c-MYC knockdown and SPLUNC1 re
      expression can down-regulate microRNA-141 (miR-141). miR-141 is up-regulated in
      NPC specimens in comparison with normal nasopharyngeal epithelium. Inhibition of
      miR-141 could affect cell cycle, apoptosis, cell growth, migration and invasion
      in NPC cells. We found that BRD3, UBAP1 and PTEN are potential targets of miR
      141, which had been confirmed following luciferase reporter assays and western
      blotting. BRD3 and UBAP1 are both involved in NPC carcinogenesis as confirmed
      through our previous studies and PTEN is a crucial tumor suppressor in many tumor
      types. BRD3 is involved in the regulation of the Rb/E2F pathway. Inhibition of
      miR-141 could affect some important molecules in the Rb/E2F, JNK2 and AKT
      pathways. It is well known that carcinogenesis of NPC is involved in the networks
      of genetic and epigenetic alteration events. We propose that miR-141- and tumor
      related genes c-MYC, SPLUNC1, BRD3, UBAP1 and PTEN may constitute a gene-miRNA
      network to contribute to NPC development.

PMID- 20053928
TI  - Common genetic variation in the sex hormone metabolic pathway and endometrial
      cancer risk: pathway-based evaluation of candidate genes.
AB  - BACKGROUND: Estrogen plays a major role in endometrial carcinogenesis, suggesting
      that common variants of genes in the sex hormone metabolic pathway may be related
      to endometrial cancer risk. In support of this view, variants in CYP19A1
      [cytochrome P450 (CYP), family 19, subfamily A, polypeptide 1] have been
      associated with both circulating estrogen levels and endometrial cancer risk.
      Associations with variants in other genes have been suggested, but findings have
      been inconsistent. METHODS: We examined 36 sex hormone-related genes using a
      tagging approach in a population-based case-control study of 417 endometrial
      cancer cases and 407 controls conducted in Poland. We evaluated common variation
      in these genes in relation to endometrial cancer risk using sequential haplotype
      scan, variable-sized sliding window and adaptive rank-truncated product (ARTP)
      methods. RESULTS: In our case-control study, the strongest association with
      endometrial cancer risk was for AR (androgen receptor; ARTP P = 0.006).
      Multilocus analyses also identified boundaries for a region of interest in AR and
      in CYP19A1 around a previously identified susceptibility loci. We did not find
      evidence for consistent associations between previously reported candidate single
      nucleotide polymorphisms in this pathway and endometrial cancer risk. DISCUSSION:
      In summary, we identified regions in AR and CYP19A1 that are of interest for
      further evaluation in relation to endometrial cancer risk in future haplotype and
      subsequent fine mapping studies in larger study populations.

PMID- 20053932
TI  - Differential effects of serotonin 5-HT1A receptor agonists on the discriminative
      stimulus effects of the 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)
      2-aminopropane in rats and rhesus monkeys.
AB  - Although many drugs act by indirectly stimulating multiple receptors (e.g.,
      reuptake inhibitors), relatively little is known about interactions between
      agonism at different receptors. This study compared the effect of serotonin (5
      HT)(1A) receptor agonists with the discriminative stimulus effects of the 5
      HT(2A) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in
      rats and rhesus monkeys. Eight rats discriminated 0.56 mg/kg i.p. DOM and
      responded under a fixed ratio (FR) 10 schedule of food presentation, whereas
      three rhesus monkeys discriminated 0.32 mg/kg s.c. DOM and responded under an FR
      5 schedule of stimulus shock termination. DOM and the 5-HT(2A) receptor agonists
      2,5-dimethoxy-4-n-propylthiophenethylamine (2C-T-7) and dipropyltryptamine (DPT),
      but not the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin
      hydrochloride (8-OH-DPAT) and 3-chloro-4-fluorophenyl-(4-fluoro-4-([(5-methyl-6
      methylaminopyridin-2-ylmethyl) amino) methyl] piperidin-1-yl) methanone (F13714),
      occasioned responding on the DOM-associated lever in rats and monkeys. Both 8-OH
      DPAT and F13714 attenuated the discriminative stimulus effects of DOM in monkeys
      but not in rats; these effects of 8-OH-DPAT and F13714 were prevented by the 5
      HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridyl)cyclohexanecarboxamide (WAY 100635). DPT and 2C-T-7 enhanced the
      discriminative stimulus effects of DOM in rats and monkeys in an additive manner.
      Taken together, the results suggest that the DOM discriminative stimulus is
      pharmacologically similar and mediated by 5-HT(2A) receptors in rats and monkeys;
      however, the ability of 5-HT(1A) receptor agonists to modify the effects of DOM
      is markedly different between these species. These results indicate possible
      differences in the neurobiology of 5-HT systems that could be important for
      studying drugs that have multiple mechanisms of action (e.g., reuptake inhibitors
      that indirectly stimulate multiple receptors).

PMID- 20053933
TI  - Transport across the blood-brain barrier of pluronic leptin.
AB  - Leptin is a peptide hormone produced primarily by adipose tissue that acts as a
      major regulator of food intake and energy homeostasis. Impaired transport of
      leptin across the blood-brain barrier (BBB) contributes to leptin resistance,
      which is a cause of obesity. Leptin as a candidate for the treatment of this
      obesity is limited because of the short half-life in circulation and the
      decreased BBB transport that arises in obesity. Chemical modification of
      polypeptides with amphiphilic poly(ethylene oxide)-poly(propylene oxide) block
      copolymers (Pluronic) is a promising technology to improve efficiency of delivery
      of polypeptides to the brain. In the present study, we determined the effects of
      Pluronic P85 (P85) with intermediate hydrophilic-lipophilic balance conjugated
      with leptin via a degradable SS bond [leptin(ss)-P85] on food intake, clearance,
      stability, and BBB uptake. The leptin(ss)-P85 exhibited biological activity when
      injected intracerebroventricularly after overnight food deprivation and 125I
      leptin(ss)-P85 was stable in blood, with a half-time clearance of 32.3 min
      (versus 5.46 min for leptin). 125I-Leptin(ss)-P85 crossed the BBB [blood-to-brain
      unidirectional influx rate (K(i)) = 0.272 +/- 0.037 microl/g x min] by a
      nonsaturable mechanism unrelated to the leptin transporter. Capillary depletion
      showed that most of the 125I-leptin(ss)-P85 taken up by the brain reached the
      brain parenchyma. Food intake was reduced when 3 mg of leptin(ss)-P85 was
      administered via tail vein in normal body weight mice [0-30 min, p < 0.0005; 0-2
      h, p < 0.001]. These studies show that the structure based Pluronic modification
      of leptin increased metabolic stability, reduced food intake, and allowed BBB
      penetration by a mechanism-independent BBB leptin transporter.

PMID- 20053934
TI  - Inhibition of inflammatory cytokine production from rheumatoid synovial
      fibroblasts by a novel IkappaB kinase inhibitor.
AB  - Nuclear factor-kappaB (NF-kappaB) is involved in the pathophysiology of
      rheumatoid arthritis (RA) and is considered to be a feasible molecular target in
      treating patients. In the RA joint tissues, activation of NF-kappaB is often
      observed together with high amounts of the proinflammatory cytokines tumor
      necrosis factor (TNF)alpha and interleukin (IL)-1beta. TNFalpha and IL-1beta are
      known to stimulate NF-kappaB signaling and are produced as the effect of NF
      kappaB signaling, thus forming a vicious cycle leading to a self-perpetuating
      nature of rheumatoid inflammation and expansion of such inflammatory response to
      other joints. Because a kinase called IkappaB kinase complex (IKK) is involved in
      the NF-kappaB activation cascade, we examined the effect of a novel IKK
      inhibitor, (7-[2-(cyclopropyl-methoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]
      1,4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride; CHPD), on the
      production of inflammatory cytokines from rheumatoid synovial fibroblasts (RSF).
      TNFalpha stimulation induced production of inflammatory cytokines such as IL-6
      and IL-8 in RSF, and the extent of IL-6 and IL-8 induction was dramatically
      reduced by CHPD under noncytotoxic concentrations. Likewise, expression of il-6
      and il-8 genes was significantly reduced by CHPD. In addition, chromatin
      immunoprecipitation assays revealed that the DNA binding of NF-kappaB (p65) to il
      8 promoter in RSF was induced after TNFalpha stimulation and that, upon CHPD
      treatment to RSF for 1 h, the NF-kappaB binding to il-8 promoter was
      significantly decreased. Here, we have demonstrated that an IKKbeta inhibitor,
      CHPD, acts as an effective inhibitor for the production of inflammatory cytokines
      in response to proinflammatory cytokines. These findings indicate that such a
      IKKbeta inhibitor could be a feasible candidate for an antirheumatic drug.

PMID- 20053935
TI  - Soy product and isoflavone intakes are associated with a lower risk of type 2
      diabetes in overweight Japanese women.
AB  - Isoflavones have been shown to improve glucose metabolism, but epidemiologic data
      are limited. We prospectively investigated the relationship between soy product
      and isoflavone intake and the risk of developing type 2 diabetes among Japanese
      adults. Participants were 25,872 men and 33,919 women aged 45-75 y, who
      participated in the second survey of the Japan Public Health Center-Based
      Prospective Study and had no history of diabetes. Soy product and isoflavone
      intakes were ascertained using a 147-item FFQ. Odds ratios of self-reported,
      physician-diagnosed type 2 diabetes over 5 y were estimated using logistic
      regression analysis. A total of 1114 new cases of type 2 diabetes were self
      reported. Intakes of soy products and isoflavones were not significantly
      associated with type 2 diabetes in either men or all women. However, among
      overweight women (BMI > or = 25 kg/m(2)), a higher intake of soy products was
      associated with a lower risk of type 2 diabetes; multivariable-adjusted odds
      ratios (95% CI) for the lowest through highest quintiles of soy product intake
      were 1.00 (reference), 0.78 (0.52-1.18), 0.79 (0.52-1.20), 0.62 (0.39-0.99), and
      0.89 (0.55-1.44), respectively, and we found a similar risk pattern for daidzein
      and genistein intakes. Overall, our results suggest that there are no benefits of
      soy product or isoflavone intake with respect to risk of type 2 diabetes in
      either men or women. The possible protective associations of soy and isoflavone
      intakes among overweight women deserves further investigation.

PMID- 20053936
TI  - Dietary phosphate restriction decreases stem cell proliferation and subsequent
      growth potential in neonatal pigs.
AB  - Although mesenchymal stem cells (MSC) and satellite cells are essential for
      postnatal muscle and bone development and phosphate (PO(4)) restriction reduces
      both muscle and skeletal tissue growth, no research to our knowledge has
      investigated the possible mechanism by which this mineral may affect early cell
      programming. Twenty piglets obtained at 1 d of age (1.8 +/- 0.3 kg) received
      either a PO(4)-adequate diet or a 25% less PO(4)-available diet over a 15-d
      trial. Feed intake and body weight were recorded daily and blood samples
      collected every 5 d. After 15 d, pigs were given an intraperitoneal injection of
      bromodeoxyuridine 4 h prior to tissue collection. As expected, PO(4) deficiency
      resulted in reduced growth (P < 0.05), feed conversion efficiency (P < 0.05), and
      bone mineral content (P < 0.05), as well as lower plasma concentrations of both
      PO(4) (P < 0.01) and parathyroid hormone (P < 0.05). In addition to these
      classical indicators of PO(4) deficiency, there was also reduced proliferation of
      both MSC (P < 0.01) and satellite cells (P < 0.05) in vivo. The expression of
      osteocalcin mRNA in bone marrow was also 2-fold greater (P < 0.01) within the
      PO(4)-adequate treatment group. These data indicate that in addition to
      reductions in muscle and bone growth, dietary PO(4) affects proliferation of
      tissue-specific stem cells in vivo. Nutritional programming of tissue-specific
      stem cells by dietary PO(4) may have profound implications for life-long growth
      potential.

PMID- 20053937
TI  - Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D
      concentrations in participants with low sun exposure and dark skin pigmentation
      is substantially higher than current recommendations.
AB  - Cutaneous cholecalciferol synthesis has not been considered in making
      recommendations for vitamin D intake. Our objective was to model the effects of
      sun exposure, vitamin D intake, and skin reflectance (pigmentation) on serum 25
      hydroxyvitamin D (25[OH]D) in young adults with a wide range of skin reflectance
      and sun exposure. Four cohorts of participants (n = 72 total) were studied for 7
      8 wk in the fall, winter, spring, and summer in Davis, CA [38.5 degrees N, 121.7
      degrees W, Elev. 49 ft (15 m)]. Skin reflectance was measured using a
      spectrophotometer, vitamin D intake using food records, and sun exposure using
      polysulfone dosimeter badges. A multiple regression model (R(2) = 0.55; P <
      0.0001) was developed and used to predict the serum 25(OH)D concentration for
      participants with low [median for African ancestry (AA)] and high [median for
      European ancestry (EA)] skin reflectance and with low [20th percentile,
      approximately 20 min/d, approximately 18% body surface area (BSA) exposed] and
      high (80th percentile, approximately 90 min/d, approximately 35% BSA exposed) sun
      exposure, assuming an intake of 200 iu/d (5 ug/d). Predicted serum 25(OH)D
      concentrations for AA individuals with low and high sun exposure in the winter
      were 24 and 42 nmol/L and in the summer were 40 and 60 nmol/L. Corresponding
      values for EA individuals were 35 and 60 nmol/L in the winter and in the summer
      were 58 and 85 nmol/L. To achieve 25(OH)D > or =75 nmol/L, we estimate that EA
      individuals with high sun exposure need 1300 iu/d vitamin D intake in the winter
      and AA individuals with low sun exposure need 2100-3100 iu/d year-round.

PMID- 20053938
TI  - Maternal multiple micronutrient supplementation has limited impact on
      micronutrient status of Bangladeshi infants compared with standard iron and folic
      acid supplementation.
AB  - Knowledge about the impact of maternal food and micronutrient supplementation on
      infant micronutrient status is limited. We examined the effect of maternal food
      and micronutrient supplementation on infant micronutrient status in the Maternal
      and Infant Nutrition Interventions in Matlab Trial. Pregnant women (n = 4436)
      were randomized to Early or Usual promotion of enrollment in a food
      supplementation program. In addition, they were randomly allocated to 1 of the
      following 3 types of daily micronutrient supplements provided from wk 14 of
      gestation to 3 mo postpartum: 1) folic acid and 30 mg iron (Fe30Fol); 2) folic
      acid and 60 mg iron; or 3) a multiple micronutrient including folic acid and 30
      mg iron (MMS). At 6 mo, infant blood samples (n = 1066) were collected and
      analyzed for hemoglobin and plasma ferritin, zinc, retinol, vitamin B-12, and
      folate. The vitamin B-12 concentration differed between the micronutrient
      supplementation groups (P = 0.049). The prevalence of vitamin B-12 deficiency was
      lower in the MMS group (26.1%) than in the Fe30Fol group (36.5%) (P = 0.003). The
      prevalence of zinc deficiency was lower in the Usual food supplementation group
      (54.1%) than in the Early group (60.2%) (P = 0.046). There were no other
      differential effects according to food or micronutrient supplementation groups.
      We conclude that maternal multiple micronutrient supplementation may have a
      beneficial effect on vitamin B-12 status in infancy.

PMID- 20053939
TI  - Broad volume distributions indicate nonsynchronized growth and suggest sudden
      collapses of germinal center B cell populations.
AB  - Immunization with a T cell-dependent Ag leads to the formation of several hundred
      germinal centers (GCs) within secondary lymphoid organs, a key process in the
      maturation of the immune response. Although prevailing perceptions about affinity
      maturation intuitively assume simultaneous seeding, growth, and decay of GCs, our
      previous mathematical simulations led us to hypothesize that their growth might
      be nonsynchronized. To investigate this, we performed computer-aided three
      dimensional reconstructions of splenic GCs to measure size distributions at
      consecutive time points following immunization of BALB/c mice with a conjugate of
      2-phenyl-oxazolone and chicken serum albumin. Our analysis reveals a broad volume
      distribution of GCs, indicating that individual GCs certainly do not obey the
      average time course of the GC volumes and that their growth is nonsynchronized.
      To address the cause and implications of this behavior, we compared our empirical
      data with simulations of a stochastic mathematical model that allows for frequent
      and sudden collapses of GCs. Strikingly, this model succeeds in reproducing the
      empirical average kinetics of GC volumes as well as the underlying broad size
      distributions. Possible causes of GC B cell population collapses are discussed in
      the context of the affinity-maturation process.

PMID- 20053940
TI  - Curvature of synthetic and natural surfaces is an important target feature in
      classical pathway complement activation.
AB  - The binding of Abs to microbial surfaces followed by complement activation
      constitutes an important line of defense against infections. In this study, we
      have investigated the relationship between complement activation and the binding
      of human IgM Abs to surfaces with different curvatures. IgM Abs to dextran were
      shown to activate complement potently on dextran-coated particles having a
      diameter around 250 nm, whereas larger (600 nm) particles were less potent
      activators. This selectivity regarding particle dimension was also found for
      complement activation by colloidal substances of microbial origin. Peptidoglycan
      (PGN) is the major chemical component in the cell wall of Gram-positive bacteria.
      Fragments of purified PGN with sizes of approximately 100 nm promoted complement
      activation effectively through the classical pathway. By contrast, larger or
      smaller fragments of PGN did not activate complement strongly. A careful analysis
      of PGN fragments released during planctonic growth of Staphylococcus aureus
      showed that these include curvatures that would permit strong IgM-mediated
      complement activation, whereas the curvature of intact cells would be less
      effective for such activation. Consistently, we found that the suspended PGN
      fragments were strong activators of complement through the classical pathway. We
      suggest that these fragments act as decoy targets for complement activation,
      providing protection for S. aureus against the host immune response to infection.

PMID- 20053941
TI  - Diabetes-induced oxidative stress is mediated by Ca2+-independent phospholipase
      A2 in neutrophils.
AB  - Neutrophils from people with poorly controlled diabetes present a primed
      phenotype and secrete excessive superoxide. Phospholipase A(2) (PLA(2))-derived
      arachidonic acid (AA) activates the assembly of NADPH oxidase to generate
      superoxide anion. There is a gap in the current literature regarding which PLA(2)
      isoform regulates NADPH oxidase activation. The aim of this study was to identify
      the PLA(2) isoform involved in the regulation of superoxide generation in
      neutrophils and investigate if PLA(2) mediates priming in response to pathologic
      hyperglycemia. Neutrophils were isolated from people with diabetes mellitus and
      healthy controls, and HL60 neutrophil-like cells were grown in hyperglycemic
      conditions. Incubating neutrophils with the Ca(2+)-independent PLA(2) (iPLA(2))
      inhibitor bromoenol lactone (BEL) completely suppressed fMLP-induced generation
      of superoxide. The nonspecific actions of BEL on phosphatidic acid
      phosphohydrolase-1, p47(phox) phosphorylation, and apoptosis were ruled out by
      specific assays. Small interfering RNA knockdown of iPLA(2) inhibited superoxide
      generation by neutrophils. Neutrophils from people with poorly controlled
      diabetes and in vitro incubation of neutrophils with high glucose and the
      receptor for advanced glycation end products ligand S100B greatly enhanced
      superoxide generation compared with controls, and this was significantly
      inhibited by BEL. A modified iPLA(2) assay, Western blotting, and PCR confirmed
      that there was increased iPLA(2) activity and expression in neutrophils from
      people with diabetes. AA (10 microM) partly rescued the inhibition of superoxide
      generation mediated by BEL, confirming that NADPH oxidase activity is, in part,
      regulated by AA. This study provides evidence for the role of iPLA(2) in enhanced
      superoxide generation in neutrophils from people with diabetes mellitus and
      presents an alternate pathway independent of protein kinase C and phosphatidic
      acid phosphohydrolase-1 hydrolase signaling.

PMID- 20053943
TI  - Expansion of FOXP3+ CD8 T cells with suppressive potential in colorectal mucosa
      following a pathogenic simian immunodeficiency virus infection correlates with
      diminished antiviral T cell response and viral control.
AB  - FOXP3(+)CD8(+) T cells are present at low levels in humans; however, the function
      of these cells is not known. In this study, we demonstrate a rapid expansion of
      CD25(+)FOXP3(+)CD8(+) regulatory T cells (Tregs) in the blood and multiple
      tissues following a pathogenic SIV infection in rhesus macaques. The expansion
      was pronounced in lymphoid and colorectal mucosal tissues, preferential sites of
      virus replication. These CD8 Tregs expressed molecules associated with immune
      suppressor function such as CTLA-4 and CD39 and suppressed proliferation of SIV
      specific T cells in vitro. They also expressed low levels of granzyme B and
      perforin, suggesting that these cells do not possess killing potential. Expansion
      of CD8 Tregs correlated directly with acute phase viremia and inversely with the
      magnitude of antiviral T cell response. Expansion was also observed in HIV
      infected humans but not in SIV-infected sooty mangabeys with high viremia,
      suggesting a direct role for hyperimmune activation and an indirect role for
      viremia in the induction of these cells. These results suggest an important but
      previously unappreciated role for CD8 Tregs in suppressing antiviral immunity
      during immunodeficiency virus infections. These results also suggest that CD8
      Tregs expand in pathogenic immunodeficiency virus infections in the nonnatural
      hosts and that therapeutic strategies that prevent expansion of these cells may
      enhance control of HIV infection.

PMID- 20053942
TI  - Ca2+ release from the endoplasmic reticulum of NY-ESO-1-specific T cells is
      modulated by the affinity of TCR and by the use of the CD8 coreceptor.
AB  - Although several cancer immunotherapy strategies are based on the use of analog
      peptides and on the modulation of the TCR affinity of adoptively transferred T
      cells, it remains unclear whether tumor-specific T cell activation by strong and
      weak TCR stimuli evoke different Ca(2+) signatures from the Ca(2+) intracellular
      stores and whether the amplitude of Ca(2+) release from the endoplasmic reticulum
      (ER) can be further modulated by coreceptor binding to peptide/MHC. In this
      study, we combined functional, structural, and kinetic measurements to correlate
      the intensity of Ca(2+) signals triggered by the stimulation of the 1G4 T cell
      clone specific to the tumor epitope NY-ESO-1(157-165). Two analogs of the NY-ESO
      1(157-165) peptide, having similar affinity to HLA-A2 molecules, but a 6-fold
      difference in binding affinity for the 1G4 TCR, resulted in different Ca(2+)
      signals and T cell activation. 1G4 stimulation by the stronger stimulus emptied
      the ER of stored Ca(2+), even in the absence of CD8 binding, resulting in
      sustained Ca(2+) influx. In contrast, the weaker stimulus induced only partial
      emptying of stored Ca(2+), resulting in significantly diminished and oscillatory
      Ca(2+) signals, which were enhanced by CD8 binding. Our data define the range of
      TCR/peptide MHC affinities required to induce depletion of Ca(2+) from
      intracellular stores and provide insights into the ability of T cells to tailor
      the use of the CD8 coreceptor to enhance Ca(2+) release from the ER. This, in
      turn, modulates Ca(2+) influx from the extracellular environment, ultimately
      controlling T cell activation.

PMID- 20053944
TI  - The affect and arousal scales: psychometric properties of the Dutch version and
      multigroup confirmatory factor analyses.
AB  - Psychometric properties of the Dutch version of the Affect and Arousal Scales
      (AFARS) were inspected in a combined clinical and population sample (N = 1,215).
      The validity of the tripartite structure and the relations between Negative
      Affect, Positive Affect, and Physiological Hyperarousal (PH) were investigated
      for boys and girls, younger (8-11 years) and older (12-14 years) children, and
      for children with high versus low levels of emotional/behavioral problems
      separately. Results demonstrated an adequate fit of the tripartite structure in
      each of the subgroups. Multigroup confirmatory factor analysis demonstrated
      parameter equivalence across sex, age, and psychopathology status. Furthermore,
      the assumption of invariant error variances of the indicator variables was
      tenable across sex, age, and psychopathology status. Invariant variances and
      covariances of the latent constructs (i.e., the tripartite factors) were
      supported across sex and psychopathology status but not across age. Finally,
      adequate item and scale properties and good convergent and moderate divergent
      validity of the Dutch AFARS subscales were demonstrated, except for the divergent
      validity of the PH subscale.

PMID- 20053945
TI  - What we talk about when we talk about buying sex.
AB  - This article explores the discourse on prostitution, trafficking, and buying sex.
      Buying sex or the purchase of sexual services, as the law says, has been a
      criminal act in Sweden since 1999. In the summer of 2006 Finland followed the
      lead, making it a crime to purchase sex from a person who has been subjected to
      trafficking or procuring. These reforms give a signal that the customers are
      responsible for increasing the international sex trade, but as the author argues,
      the commercial language used by the law makers may be a double-edged sword.

PMID- 20053946
TI  - The ability of criminal law to produce gender equality: judicial discourses in
      the Swedish criminal legal system.
AB  - The main aim of the Swedish Women's Peace reform in 1998 was to enhance criminal
      legal protection for women exposed to violence in heterosexual relationships and
      to promote gender equality. However, these ambitions risk being contravened in a
      masculinist criminal legal system. One problem concerns how the victim is
      constructed in criminal legal cases. The author argues that moral balancing and
      discourses of responsibility and guilt in Swedish cases constrain the agency
      possible for women and suggest that a more comprehensive policy in Sweden must be
      developed to include violent men, their agency, and their responsibility for the
      violence.

PMID- 20053947
TI  - "Keeping up a front": narratives about intimate partner violence, pregnancy, and
      antenatal care.
AB  - Nine women who had been subjected to severe intimate partner violence during
      pregnancy narrated their ambiguous and contradictory feelings and the various
      balancing strategies they used to overcome their complex and difficult
      situations. Because allowing anyone to come close posed a threat, the women
      mostly denied the situation and kept up a front to hide the violence from others.
      Three women disclosed ongoing violence to the midwives, but only one said such
      disclosure was helpful. This article highlights the complexity of being pregnant
      when living with an abusive partner and challenges antenatal care policies from
      the perspective of pregnant women.

PMID- 20053948
TI  - "He messed me up": Swedish adolescent girls' experiences of gender-related
      partner violence and its consequences over time.
AB  - This article illuminates two Swedish adolescent girls' experiences of living in a
      violent relationship as teenagers and how this has affected their lives and
      health over time. Interviews were conducted in a youth health center. A
      combination of qualitative content analysis and narrative analysis describes
      violation, stress, trauma, coping, and agency during the period of adolescence
      and transition into adulthood. Despite Swedish progressive public policies on
      men's violence against women, teenage girls are exposed to male partners'
      violation, a severe gendered stressor. There is a need for the development of
      health policy and gender-responsive interventions geared specifically toward
      adolescent girls.

PMID- 20053949
TI  - Long-term TENS treatment improves tactile sensitivity in MS patients.
AB  - BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is commonly used
      in neurorehabilitation for the treatment of pain and spasticity. OBJECTIVE: The
      long-term effects of sensory stimulation by means of TENS on hand sensitivity
      were investigated in patients with multiple sclerosis (MS). METHODS: TENS was
      applied for 3 weeks (1 hour per day) on the median nerve region of the dominant
      hand. Sensitivity was assessed by the Semmes-Weinstein monofilaments before and
      12 hours following the last intervention as well as 3 weeks later. RESULTS: Long
      lasting increases in tactile sensitivity were achieved by repetitive stimulation
      of sensory afferents with TENS in MS patients but not in healthy subjects. This
      increased sensitivity was not only restricted to the median nerve area but also
      expanded to the ulnar nerve area. Remarkably, MS patients reached the same level
      of sensitivity as healthy subjects immediately after the intervention, and long
      term effects were reported 3 weeks later. CONCLUSIONS: The findings of this study
      demonstrated lasting improvements in tactile sensitivity of the fingers as a
      result of a long-term TENS intervention in MS patients, who ultimately reached a
      level comparable with that of healthy subjects.

PMID- 20053950
TI  - Minimal detectable change and clinically important difference of the Stroke
      Impact Scale in stroke patients.
AB  - OBJECTIVES: The purpose of this study was to establish the minimal detectable
      change (MDC) and clinically important differences (CIDs) of the physical domains
      of the Stroke Impact Scale (SIS) and to assess the proportions of patients'
      change scores exceeding the MDC and CIDs after stroke rehabilitation. METHODS:
      Seventy-four patients received 1 of 3 treatments for 3 weeks and underwent
      clinical assessment before and after treatment. The MDC was calculated from the
      standard error of measurement to indicate a real change with 95% confidence for
      individual patients (MDC(95)). Anchor-based and distribution-based approaches
      were adopted to triangulate the ranges of minimal CIDs. The percentage of
      patients exceeding MDC(95) and minimal CIDs were also calculated. RESULTS: The
      MDC(95) of the strength, activities of daily living/instrumental activities of
      daily living, mobility, and hand function subscales were 24.0, 17.3, 15.1, and
      25.9, respectively. The respective minimal CIDs for these 4 subscales were 9.2,
      5.9, 4.5, and 17.8 points, respectively, and the MDC(95) and CID proportions were
      14% to 43%, 16% to 49%, 10% to 50%, and 23% to 64%, respectively. CONCLUSIONS:
      The change score of an individual patient has to reach 24.0, 17.3, 15.1, and 25.9
      on the 4 subscales to indicate a true change. The mean change scores of a stroke
      group on the 4 subscales should reach 9.2, 5.9, 4.5, and 17.8 points to be
      regarded as clinically important changes. Future research with larger sample
      sizes is warranted to validate these estimates.

PMID- 20053951
TI  - Task-oriented biofeedback to improve gait in individuals with chronic stroke:
      motor learning approach.
AB  - BACKGROUND: Electromyographic biofeedback (EMG-BFB) has shown equivocal benefits
      on gait retraining after stroke. OBJECTIVE: The authors evaluated the efficacy of
      EMG-BFB applied in a task-oriented approach based on principles of motor learning
      to increase peak ankle power of the affected leg and gait velocity in patients
      with chronic mild to moderate hemiparesis. METHODS: They assigned 20 participants
      randomly to the EMG-BFB group or a control group that received conventional
      therapy for the same duration. Quantitative gait analysis was performed before
      and after treatment. The EMG-BFB involved the triceps surae during functional
      gait activities. Treatment was administered with a fading frequency of BFB
      application and an increasing variability in gait activities. Both groups had 20
      treatment sessions of 45 minutes each, including at least 15 minutes of walking
      related therapy for the control group. Follow-up (FU) gait analysis was obtained
      6 weeks after training. RESULTS: BFB treatment led to significant increases (P <
      .01) in peak ankle power at push-off (from 0.63 W/kg to 1.04 W/kg) in conjunction
      with significant increases in velocity (from 28.3 %h/s--normalized to percentage
      height per second--to 39.6 %h/s) and stride length (from 44.5 %h--normalized to
      percentage height--to 57.6 %h). Increases remained significant at FU. There were
      no changes in any gait variable in the control group. CONCLUSION: A task-oriented
      BFB treatment was effective in increasing peak ankle power, gait velocity, and
      stride length in a population with hemiparesis. Further studies should compare
      the combination intervention with either of its components in more impaired
      patients.

PMID- 20053952
TI  - Reduction of spasticity with repetitive transcranial magnetic stimulation in
      patients with spinal cord injury.
AB  - OBJECTIVE: Spasticity with increased tone and spasms is frequent in patients
      after spinal cord injury (SCI). Damage to descending corticospinal pathways that
      normally exert spinal segmental control is thought to play an important causal
      role in spasticity. The authors examined whether the modulation of excitability
      of the primary motor cortex with high-frequency repetitive transcranial magnetic
      stimulation (rTMS) could modify lower limb spasticity in patients with incomplete
      SCI. METHODS: Patients were assessed by the Modified Ashworth Scale, Visual
      Analogue Scale, and the Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET)
      and neurophysiologically with measures of corticospinal and segmental
      excitability by the H(max)/M(max), T reflex, and withdrawal reflex. Fifteen
      patients received 5 days of daily sessions of active (n = 14) or sham (n = 7)
      rTMS to the leg motor area (20 trains of 40 pulses at 20 Hz and an intensity of
      90% of resting motor threshold for the biceps brachii muscle). RESULT: A
      significant clinical improvement in lower limb spasticity was observed in
      patients following active rTMS but not after sham stimulation.This improvement
      lasted for at least 1 week following the intervention. Neurophysiological studies
      did not change. CONCLUSIONS: High-frequency rTMS over the leg motor area can
      improve aspects of spasticity in patients with incomplete SCI.

PMID- 20053953
TI  - Distinguishing features of cuban children referred for professional help because
      of ADHD: looking beyond the symptoms.
AB  - OBJECTIVE: To distinguish Cuban children clinically referred because of ADHD from
      an at-risk community sample and a community control group in terms of symptoms,
      associated difficulties and impairment of family and peer relations. METHOD:
      Parents and teachers of 1,036 children (6-8 years old) completed an established
      ADHD rating scale and a behavioral screening measure, including peer
      functioning.We also administered a structured clinical interview and measures of
      family impairment to the clinical sample and to an at-risk community-based
      subsample. RESULTS: Although both clinical and at-risk groups displayed more
      externalizing and internalizing symptoms than controls, referred children were
      not only characterized by higher levels of ADHD symptoms, but also by greater
      impairment of family and peer relations than at-risk community children or
      community controls. CONCLUSION: The findings suggest that ADHD has major
      consequences on the family and peer functioning of Cuban children, which may lead
      to their referral for treatment.

PMID- 20053954
TI  - Detergent-resistant microdomains determine the localization of sigma-1 receptors
      to the endoplasmic reticulum-mitochondria junction.
AB  - Sigma-1 receptors (Sig-1Rs) that bind diverse synthetic and endogenous compounds
      have been implicated in the pathophysiology of several human diseases such as
      drug addiction, depression, neurodegenerative disorders, pain-related disorders,
      and cancer. Sig-1Rs were identified recently as novel ligand-operated molecular
      chaperones. Although Sig-1Rs are predominantly expressed at endoplasmic reticulum
      (ER) subdomains apposing mitochondria [i.e., the mitochondria-associated ER
      membrane (MAM)], they dynamically change the cellular distribution, thus
      regulating both MAM-specific and plasma membrane proteins. However, what
      determines the location of Sig-1R at the MAM and how the receptor translocation
      is initiated is unknown. Here we report that the detergent-resistant membranes
      (DRMs) play an important role in anchoring Sig-1Rs to the MAM. The MAM, which is
      highly capable of accumulating ceramides, is enriched with both cholesterol and
      simple sphingolipids, thus forming Triton X-114-resistant DRMs. Sig-1Rs associate
      with MAM-derived DRMs but not with those from microsomes. A lipid overlay assay
      found that solubilized Sig-1Rs preferentially associate with simple sphingolipids
      such as ceramides. Disrupting DRMs by lowering cholesterol or inhibiting de novo
      synthesis of ceramides at the ER largely decreases Sig-1R at DRMs and causes
      translocation of Sig-1R from the MAM to ER cisternae. These findings suggest that
      the MAM, bearing cholesterol and ceramide-enriched microdomains at the ER, may
      use the microdomains to anchor Sig-1Rs to the location; thus, it serves to stage
      Sig-1R at ER-mitochondria junctions.

PMID- 20053955
TI  - Carbon monoxide releasing molecule-2 inhibits pancreatic stellate cell
      proliferation by activating p38 mitogen-activated protein kinase/heme oxygenase-1
      signaling.
AB  - Proliferation of pancreatic stellate cells (PSCs) plays a cardinal role during
      fibrosis development. Therefore, the suppression of PSC growth represents a
      therapeutic option for the treatment of pancreatic fibrosis. It has been shown
      that up-regulation of the enzyme heme oxygenase-1 (HO-1) could exert
      antiproliferative effects on PSCs, but no information is available on the
      possible role of carbon monoxide (CO), a catalytic byproduct of the HO
      metabolism, in this process. In the present study, we have examined the effect of
      CO releasing molecule-2 (CORM-2) liberated CO on PSC proliferation and have
      elucidated the mechanisms involved. Using primary rat PSCs, we found that CORM-2
      inhibited PSC proliferation at nontoxic concentrations by arresting cells at the
      G(0)/G(1) phase of the cell cycle. This effect was associated with activation of
      p38 mitogen-activated protein kinase (MAPK) signaling, induction of HO-1 protein,
      and up-regulation of the cell cycle inhibitor p21(Waf1/Cip1). The p38 MAPK
      inhibitor 4-(4-flurophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)imidazole
      (SB203580) abolished the inhibitory effect of CORM-2 on PSC proliferation and
      prevented both CORM-2-induced HO-1 and p21(Waf1/Cip1) up-regulation. Treatment
      with tin protoporphyrin IX, an HO inhibitor, or transfection of HO-1 small
      interfering RNA abolished the inductive effect of CORM-2 on p21(Waf1/Cip1) and
      reversed the suppressive effect of CORM-2 on PSC growth. The ability of CORM-2 to
      induce cell cycle arrest was abrogated in p21(Waf1/Cip1)-silenced cells. Taken
      together, our results suggest that CORM-2 inhibits PSC proliferation by
      activation of the p38/HO-1 pathway. These findings may indicate a therapeutic
      potential of CO carriers in the treatment of pancreatic fibrosis.

PMID- 20053956
TI  - NOX2 is the primary source of angiotensin II-induced superoxide in the macula
      densa.
AB  - Macula densa (MD)-mediated regulation of renal hemodynamics via tubuloglomerular
      feedback is regulated by interactions between factors such as superoxide (O(2)(
      )) and angiotensin II (ANG II). We have reported that NaCl-induced O(2)(-) in the
      MD is produced by the NOX2 isoform of NADPH oxidase (NOX); however, the source of
      ANG II-induced O(2)(-) in MD is unknown. Thus we determined the pathways by which
      ANG II increased O(2)(-) in the MD by measuring O(2)(-) in ANG II-treated MMDD1
      cells, a MD-like cell line. ANG II caused MMDD1 O(2)(-) levels to increase by
      more than twofold (P < 0.01). This increase was blocked by losartan (AT(1)
      receptor blocker) but not PD-123319 (AT(2) receptor antagonist). Apocynin (a NOX
      inhibitor) decreased O(2)(-) by 86% (P < 0.01), whereas oxypurinol (a xanthine
      oxidase inhibitor) and NS-398 (a cyclooxygenase-2 inhibitor) had no significant
      effect. The NOX-dependent increase in O(2)(-) was due to the NOX2 isoform; a
      short interfering (si)RNA against NOX2 blunted ANG II-induced increases in O(2)(
      ), whereas the NOX4/siRNA did not. Finally, we found that inhibiting the Rac1
      subunit of NOX blunted ANG II-induced O(2)(-) production in NOX4/siRNA-treated
      cells but did not further decrease it in NOX2/siRNA-treated cells. Our results
      indicate that ANG II stimulates O(2)(-) production in the MD primarily via AT(1)
      dependent activation of NOX2. Rac1 is required for the full activation of NOX2.
      This pathway may be an important component of ANG II enhancement of
      tubuloglomerular feedback.

PMID- 20053957
TI  - Prokineticin 2 modulates the excitability of area postrema neurons in vitro in
      the rat.
AB  - Despite recent evidence describing prokineticin 2 (PK2)-producing neurons and
      receptors in the dorsomedial medulla, little is known regarding the potential
      mechanisms by which this circadian neuropeptide acts in the medulla to influence
      autonomic function. Using whole cell electrophysiology, we have investigated a
      potential role for PK2 in the regulation of excitability in neurons of the area
      postrema (AP), a medullary structure known to influence autonomic processes in
      the central nervous system. In current-clamp recordings, focal application of 1
      microM PK2 reversibly influenced the excitability of the majority of dissociated
      AP cells tested, producing depolarizations (38%) and hyperpolarizations (28%) in
      a concentration-dependent manner. Slow voltage ramps and ion-substitution
      experiments revealed that a PK2-induced Cl(-) current was responsible for
      membrane depolarization, whereas hyperpolarizations were the result of inhibition
      of a nonselective cation current. In contrast to these differential effects on
      membrane potential, nearly all neurons that displayed spontaneous activity
      responded to PK2 with a decrease in spike frequency. These observations are in
      accordance with voltage-clamp experiments showing that PK2 caused a leftward
      shift in Na(+) channel activation and inactivation gating. Lastly, using post hoc
      single-cell RT-PCR technology, we have shown that 7 of 10 enkephalin-expressing
      AP neurons were depolarized by PK2 indicating that PK2 may have specific
      inhibitory actions on this population of neurons in the AP to reduce their
      sensitivity to homeostatic signals. These data suggest that the level of AP
      neuronal excitability may be regulated by PK2, ultimately affecting AP autonomic
      control.

PMID- 20053959
TI  - Interleukin-10 reduces inflammation, endothelial dysfunction, and blood pressure
      in hypertensive pregnant rats.
AB  - Hypertensive disorders of pregnancy are characterized by systemic and placental
      inflammation; however, treatment for these conditions has remained elusive. We
      tested whether administration of the anti-inflammatory cytokine interleukin-10
      (IL-10) during pregnancy would attenuate the hypertension, endothelial
      dysfunction, proteinuria, and inflammation seen in pregnant DOCA/saline-treated
      (PDS) rats. Normal pregnant (NP) rats and PDS were given daily intraperitoneal
      injections of recombinant IL-10 from gestational day 13 until death on day 20.
      Systolic blood pressure, aortic endothelium-dependent relaxation responses, and
      urinary protein excretion were measured on days 13 and 20 of gestation. Fetal
      number and development, plasma endothelin-1 levels, serum and placental levels of
      IFNgamma and IL-10, and aortic and placental levels of platelet endothelial cell
      adhesion molecule (PECAM) were assessed on gestational day 20. Systolic blood
      pressure, aortic endothelial dysfunction, and urinary protein excretion were
      significantly increased at gestational day 13 in PDS rats. However, all of these
      were restored to NP levels following IL-10 treatment in PDS rats. IL-10 treatment
      also significantly increased the number of pups per litter in PDS rats and did
      not further affect fetal development. The beneficial effects of IL-10 in PDS rats
      were likely mediated by the decreased plasma levels of endothelin-1, decreased
      levels of circulating and placental IFNgamma, as well as decreased aortic and
      placental expression of PECAM. These data demonstrate that exogenous IL-10 can
      normalize blood pressure and endothelial function in pregnancy-induced
      hypertensive rats and may be beneficial in women with hypertensive disorders of
      pregnancy.

PMID- 20053960
TI  - Endothelin in the female vasculature: a role in aging?
AB  - Cardiovascular diseases are the leading cause of morbidity and mortality in the
      world. Aging is associated with an increased incidence of cardiovascular disease.
      Premenopausal women are relatively protected from vascular alterations compared
      with age-matched men, likely due to higher levels of the female sex hormones.
      However, these vasoprotective effects in women are attenuated after menopause.
      Thus, the vascular system in aging women is affected by both the aging process as
      well as loss of hormonal protection, positioning women of this age group at a
      high risk for cardiovascular diseases such as hypertension, myocardial
      infarction, and stroke. The endothelin system in general and endothelin-1 (ET-1)
      in particular plays an important role in the pathogenesis of vascular dysfunction
      associated with aging. Evidence suggests that the female sex steroids can
      interfere with the vascular expression and actions of ET-1 via several
      mechanisms, which may further contribute to pathological processes in the
      vasculature of aging women. In this review, we have summarized hormone-dependent
      vascular pathways whereby ET-1 may mediate the deleterious effects of aging in
      postmenopausal females.

PMID- 20053958
TI  - Exocytosis mechanisms underlying insulin release and glucose uptake: conserved
      roles for Munc18c and syntaxin 4.
AB  - Type 2 diabetes has been coined "a two-hit disease," as it involves specific
      defects of glucose-stimulated insulin secretion from the pancreatic beta cells in
      addition to defects in peripheral tissue insulin action required for glucose
      uptake. Both of these processes, insulin secretion and glucose uptake, are
      mediated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor) protein core complexes composed of syntaxin, SNAP-23/25, and VAMP
      proteins. The SNARE core complex is regulated by the Sec1/Munc18 (SM) family of
      proteins, which selectively bind to their cognate syntaxin isoforms with high
      affinity. The process of insulin secretion uses multiple Munc18-syntaxin isoform
      pairs, whereas insulin action in the peripheral tissues appears to use only the
      Munc18c-syntaxin 4 pair. Importantly, recent reports have linked obesity and Type
      2 diabetes in humans with changes in protein levels and single nucleotide
      polymorphisms (SNPs) of Munc18 and syntaxin isoforms relevant to these exocytotic
      processes, although the molecular mechanisms underlying the observed phenotypes
      remain incomplete (5, 104, 144). Given the conservation of these proteins in two
      seemingly disparate processes and the need to design and implement novel and more
      effective clinical interventions, it will be vitally important to delineate the
      mechanisms governing these conserved SNARE-mediated exocytosis events. Thus, we
      provide here an up-to-date historical review of advancements in defining the
      roles and molecular mechanisms of Munc18-syntaxin complexes in the
      pathophysiology of Type 2 diabetes.

PMID- 20053962
TI  - Mechanisms of endothelium-dependent vasodilation in male and female, young and
      aged offspring born growth restricted.
AB  - Numerous epidemiological studies have shown that cardiovascular dysfunction in
      adult life may be programmed by compromised growth in utero. Aging is a risk
      factor for vascular endothelial-dependent dysfunction. After birth, the impact of
      intrauterine growth restriction (IUGR) on normal aging mechanisms of vascular
      dysfunction is not known. We hypothesized that IUGR would cause changes in
      vascular function that would affect the mechanisms of endothelium-dependent
      vasodilation later in life in an age- or sex-dependent manner. To create an IUGR
      model, pregnant Sprague-Dawley rats were placed in a hypoxic (12% O(2)) or
      control (room air, 21% O(2)) environment from days 15 to 21 of the pregnancy, and
      both male and female offspring were investigated at 4 or 12 mo of age.
      Endothelial function was assessed in small mesenteric arteries using methacholine
      (MCh)-induced vasodilation in a wire myograph system. The involvement of nitric
      oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF)
      was assessed using the inhibitors N(omega)-nitro-l-arginine methyl ester
      hydrochloride, meclofenamate, or a combination of apamin and TRAM-34 (SK(Ca) and
      IK(Ca) blockers), respectively. EDHF-induced vasodilation was further
      investigated by using inhibitors of P450 epoxygenases [N-methylsulfonyl-6-(2
      propargyloxyphenyl) hexanamide] and gap junctions (18alpha-glycyrrhetinic acid).
      NO-mediated vasodilation was significantly reduced in aged controls and both
      young and aged IUGR females. EDHF-mediated vasodilation was maintained in all
      groups; however, an additional involvement of gap junctions was found in females
      exposed to hypoxia in utero, which may represent a compensatory mechanism. A
      change in the mechanisms of vasodilation occurring at an earlier age in IUGR
      offspring may predispose them to adult cardiovascular diseases.

PMID- 20053961
TI  - The cellular force-frequency response in ventricular myocytes from the varanid
      lizard, Varanus exanthematicus.
AB  - To investigate the cellular mechanisms underlying the negative force-frequency
      relationship (FFR) in the ventricle of the varanid lizard, Varanus
      exanthematicus, we measured sarcomere and cell shortening, intracellular Ca(2+)
      ([Ca(2+)](i)), action potentials (APs), and K(+) currents in isolated ventricular
      myocytes. Experiments were conducted between 0.2 and 1.0 Hz, which spans the
      physiological range of in vivo heart rates at 20-22 degrees C for this species.
      As stimulation frequency increased, diastolic length, percent change in sarcomere
      length, and relaxation time all decreased significantly. Shortening velocity was
      unaffected. These changes corresponded to a faster rate of rise of [Ca(2+)](i), a
      decrease in [Ca(2+)](i) transient amplitude, and a seven-fold increase in
      diastolic [Ca(2+)](i). The time constant for the decay of the Ca(2+) transient
      (tau) decreased at higher frequencies, indicating a frequency-dependent
      acceleration of relaxation (FDAR) but then reached a plateau at moderate
      frequencies and did not change above 0.5 Hz. The rate of rise of the AP was
      unaffected, but the AP duration (APD) decreased with increasing frequency. Peak
      depolarization tended to decrease, but it was only significant at 1.0 Hz. The
      decrease in APD was not due to frequency-dependent changes in the delayed inward
      rectifier (I(Kr)) or the transient outward (I(to)) current, as neither appeared
      to be present in varanid ventricular myocytes. Our results suggest that a
      negative FFR relationship in varanid lizard ventricle is caused by decreased
      amplitude of the Ca(2+) transient coupled with an increase in diastolic Ca(2+),
      which leads to incomplete relaxation between beats at high frequencies. This
      coincides with shortened APD at higher frequencies.

PMID- 20053963
TI  - Regulation of circadian gene expression in the kidney by light and food cues in
      rats.
AB  - Although studies involving the circadian response to external time cues indicate
      that the peripheral clocks are dominated mainly by food cues, whether and how
      changes in the light and food cues affect the circadian rhythm of the renal clock
      is still largely unknown. In the present study, we found that the circadian
      phases of Bmal1, Clock, Cry1, Per1, and Per2 were altered differently by the
      stimuli of food and light cues in the kidney. After the individual reversal of
      the light-dark (LD) cycle for 7 days, Per1 displayed a 4-h phase delay, whereas
      the peak phases of Bmal1, Clock, Cry1 and Per2 almost remained the same as those
      in the control condition. With regard to the feeding-induced circadian resetting
      of the renal clock, we found that the resetting processes of clock genes could
      not be completed within 7 days, suggesting a weak synchronization effect of the
      food cue on the renal circadian clock. Moreover, the reentrainment of the clock
      genes was greatly enhanced after the reversal of both the feeding schedule and
      the LD cycle. Noticeably, the phases of Per1 and Clock were shifted most rapidly
      by 12 h within 3 days after the simultaneous reversal of the feeding schedule and
      the LD cycle, whereas their peak phases were only shifted by 4 h and 8 h,
      respectively, on the 7th day after the individual reversal of the feeding
      schedule. Thus Per1 and Clock may play important roles in the light-induced
      resetting of the circadian rhythms in the kidney.

PMID- 20053964
TI  - Periconceptional undernutrition and being a twin each alter kidney development in
      the sheep fetus during early gestation.
AB  - Adaptive growth responses of the embryo and fetus to nutritional restraint are
      important in ensuring early survival, but they are implicated in the programming
      of hypertension. It has been demonstrated that kidney growth and nephrogenesis
      are each regulated by intrarenal factors, including the insulin-like growth
      factors, glucocorticoids, and the renin-angiotensin system. Therefore, we have
      investigated the impact of periconceptional undernutrition (PCUN; from
      approximately 6 wk before to 7 days after conception) in singleton (control, n =
      18; PCUN, n = 16) and twin pregnancies (control, n = 6; PCUN, n = 5) on the renal
      mRNA expression of 11beta- hydroxysteroid dehydrogensase type 1 and type 2
      (11beta-HSD-1 and -2), the glucocorticoid (GR), and mineralocorticoid receptors,
      angiotensinogen, angiotensin receptor type 1 (AT1R) and 2 (AT2R), IGF-1 and IGF
      2, and IGF1R and IGF2R at approximately 55 days gestation. There was no effect of
      PCUN or fetal number on fetal weight on relative kidney weight at approximately
      day 55 of gestation. There was an inverse relationship between the relative
      weight of the fetal kidney at approximately day 55 and maternal weight loss
      during the periconceptional period in fetuses exposed to PCUN. Exposure to PCUN
      resulted in a higher expression of IGF1 in the fetal kidney in singleton and twin
      pregnancies. Being a twin resulted in higher intrarenal expression of IGF-1 and
      IGF-2, GR, angiotensinogen, AT1R, and AT2R mRNA at 55 days gestation. Renal
      11beta-HSD-2 mRNA expression was higher in PCUN singletons, but not PCUN twins,
      compared with controls. Thus, there may be an adaptive response in the kidney to
      the early environment of a twin pregnancy, which precedes the fetal growth
      restriction that occurs later in pregnancy. The kidney of the twin fetus exposed
      to periconceptional undernutrition may also be less protected from the
      consequences of glucocorticoid exposure.

PMID- 20053965
TI  - Role of mutation of the circadian clock gene Per2 in cardiovascular circadian
      rhythms.
AB  - Alterations in the circadian blood pressure pattern are frequently observed in
      hypertension and lead to increased cardiovascular morbidity. However, there are
      no studies that have investigated a possible implication of the Period2 gene, a
      key component of the molecular circadian clock, on the circadian rhythms of blood
      pressure and heart rate. To address this question, we monitored blood pressure,
      heart rate, and locomotor activity 24 h a day by telemetry in mice carrying a
      mutation in the Period2 gene and in wild-type control mice. Under a standard
      12:12-h light-dark cycle, mutant mice showed a mild cardiovascular phenotype with
      an elevated 24-h heart rate, a decreased 24-h diastolic blood pressure, and an
      attenuation of the dark-light difference in blood pressure and heart rate.
      Locomotor activity was similar in both groups and did not appear to explain the
      observed hemodynamic differences. When mice were placed under constant darkness
      during eight consecutive days, wild-type mice maintained 24-h rhythms, whereas
      there was an apparent progressive loss of 24-h rhythm of blood pressure, heart
      rate, and locomotor activity in mutant mice. However, a chi square periodogram
      revealed that circadian rhythms were preserved under complete absence of any
      light cue, but with shorter periods by approximately 40 min, leading to a
      cumulative phase shift toward earlier times of approximately 5 h and 20 min by
      the end of the 8th day. When heart rate, mean arterial pressure, and activity
      were recalculated according to the endogenous circadian periods of each
      individual mouse, the amplitudes of the circadian rhythms ("subjective night"
      "subjective day" differences) were maintained for all variables studied. Our data
      show that mutation of the Period2 gene results in an attenuated dipping of blood
      pressure and heart rate during both light-dark cycles and constant darkness, and
      in shorter circadian periods during constant darkness.

PMID- 20053966
TI  - Early effects of doxorubicin in perfused heart: transcriptional profiling reveals
      inhibition of cellular stress response genes.
AB  - Doxorubicin (DXR) belongs to the most efficient anticancer drugs. However, its
      clinical application is limited by the risk of severe cardiac-specific toxicity,
      for which an efficient treatment is missing. Underlying molecular mechanisms are
      not sufficiently understood so far, but nonbiased, systemic approaches can yield
      new clues to develop targeted therapies. Here, we applied a genome-wide
      transcriptome analysis to determine the early cardiac response to DXR in a model
      characterized earlier, that is, rat heart perfusion with 2 muM DXR, leading to
      only mild cardiac dysfunction. Single-gene and gene set enrichment analysis of
      DNA microarrays yielded robust data on cardiac transcriptional reprogramming,
      including novel DXR-responsive pathways. Main characteristics of transcriptional
      reprogramming were 1) selective upregulation of individual genes or gene sets
      together with widespread downregulation of gene expression; 2) repression of
      numerous transcripts involved in cardiac stress response and stress signaling; 3)
      modulation of genes with cardiac remodeling capacity; 4) upregulation of "energy
      related" pathways; and 5) similarities to the transcriptional response of cancer
      cells. Some early responses like the induction of glycolytic and Krebs cycle
      genes may have compensatory function. Only minor changes in the cardiac energy
      status or the respiratory activity of permeabilized cardiac fibers have been
      observed. Other responses potentially contribute to acute and also chronic
      toxicity, in particular, those in stress-responsive and cardiac remodeling
      transcripts. We propose that a blunted response to stress and reduced "danger
      signaling" is a prime component of toxic DXR action and can drive cardiac cells
      into pathology.

PMID- 20053967
TI  - Acute exacerbations of chronic obstructive pulmonary disease: are antibiotics
      needed?

PMID- 20053968
TI  - Loop gain in apnea: gaining control or controlling the gain?

PMID- 20053969
TI  - A role for genes and environment in the causal relationship between infant RSV
      infection and childhood asthma.

PMID- 20053970
TI  - The beta-agonist saga.

PMID- 20053971
TI  - Does finding M. Tuberculosis in sputum always equal tuberculosis disease?

PMID- 20053972
TI  - Physicochemical properties affecting retinal drug/coumarin-6 delivery from
      nanocarrier systems via eyedrop administration.
AB  - PURPOSE: To elucidate the effect of physicochemical properties of nanocarrier
      systems on drug delivery efficiency to the retina by eyedrop administration in
      mice, rabbits, and monkeys. METHODS: Submicron-sized liposomes (ssLips) of
      different particle size, cholesterol content, surface charge, and multilamellar
      vesicles (MLV) were prepared by the hydration METHOD: Fluorescence probe
      (coumarin-6)-incorporated liposomes, lipid emulsions, and FITC-labeled
      polystyrene particles were used to investigate their intraocular behavior after
      eyedrop administration, using epifluorescence microscopy in mice, rabbits, and
      monkeys. RESULTS: Delivery efficiency of fluorescent probes to the mouse retina
      from dropped liposomes was extensively improved by reducing their particle size
      (<600 nm) and cholesterol content, whereas negligible improvement was observed in
      the case of MLV. Furthermore, FITC-labeled polystyrene particles and coumarin-6
      incorporated lipid emulsions showed an insufficient effect on retinal delivery in
      mice even if their size was controlled at 110 nm. The highest accumulation of the
      fluorescent probe in the retina was observed around 30 minutes with any type of
      ssLip used, followed by the prompt disappearance of their fluorescence within 120
      minutes in mice. Changes in the fluorescence intensity of coumarin-6 in rabbits
      and monkeys were observed in a manner similar to that described in mice. Retinal
      flat-mount images suggest that coumarin-6 incorporated in ssLip diffused from the
      iris and ciliary body side to the optic disc side in the retina after eyedrop
      administration. CONCLUSIONS: The delivery efficiency of coumarin-6 to the retina
      was altered depending on particle size, constituents, and rigidity. ssLips with
      appropriate features would be promising drug carriers for retinal delivery
      through eyedrops.

PMID- 20053973
TI  - Age-dependent deamidation of lifelong proteins in the human lens.
AB  - PURPOSE: Deamidation is a common posttranslational modification in human lens
      crystallins and may be a key factor in the age-related denaturation of such
      lifelong proteins. The aim of this study was to identify the sites of deamidation
      in older lenses. METHODS: High-performance liquid chromatography/mass
      spectrometry of tryptic digests was used to identify sites of deamidation in the
      major human lens crystallins. Older normal and age-matched cataractous lenses
      were compared with fetal lenses. RESULTS: Approximately equal numbers of
      glutamine and asparagine residues were deamidated in older lenses; however, the
      extent of deamidation of Asn was three times greater than that of Gln (Asn, 22.6%
      +/- 3.6%; Gln, 6.6% +/- 1.3%). Individual crystallins differed markedly in their
      extent of deamidation, and deamidated residues were typically localized within
      discrete regions of the polypeptides. A large percentage (42%) of the sites of
      deamidation were characterized by the presence of a basic amino acid one residue
      removed from the original Gln or Asn. At nine such sites, the extent of Asn
      deamidation averaged 50% in aged lenses. There were few differences in
      deamidation between crystallins of aged normal and nuclear cataractous lenses.
      CONCLUSIONS: Equal numbers of Asn and Gln residues are deamidated in crystallins
      from aged normal and cataractous lenses. Deamidation of Asn/Gln in lifelong
      proteins, such as those in the lens, may be governed to a significant degree by
      base-catalyzed processes.

PMID- 20053974
TI  - Mutation discovered in a feline model of human congenital retinal blinding
      disease.
AB  - PURPOSE: To elucidate the gene defect in a pedigree of cats segregating for
      autosomal dominant rod-cone dysplasia (Rdy), a retinopathy characterized
      extensively from a clinical perspective. Disease expression in Rdy cats is
      comparable to that in young patients with congenital blindness (Leber congenital
      amaurosis [LCA] or retinitis pigmentosa [RP]). METHODS: A pedigree segregating
      for Rdy was generated and phenotyped by clinical ophthalmic examination methods
      including ophthalmoscopy and full-field flash electroretinography. Short tandem
      repeat loci tightly linked to candidate genes for autosomal dominant retinitis
      pigmentosa in humans were genotyped in the pedigree. RESULTS: Significant linkage
      was established to the candidate gene CRX (LOD = 5.56, = 0) on cat chromosome E2.
      A single base pair deletion was identified in exon 4 (n.546delC) in affected
      individuals but not in unaffected littermates. This mutation generates a frame
      shift in the transcript, introducing a premature stop codon truncating the
      putative CRX peptide, which would eliminate the critical transcriptional
      activation region. Clinical observations corroborate previously reported clinical
      reports about Rdy. Results show that the cone photoreceptor system was more
      severely affected than the rods in the early disease process. CONCLUSIONS: A
      putative mutation causative of the Rdy phenotype has been described as a single
      base pair deletion in exon 4 of the CRX gene, thus identifying the first animal
      model for CRX-linked disease that closely resembles the human disease. As such,
      it will provide valuable insights into the mechanisms underlying these diseases
      and their variable presentation, as well as providing a suitable model for
      testing therapies for these diseases.

PMID- 20053975
TI  - Aqueous humor levels of hepatocyte growth factor in retinitis pigmentosa.
AB  - PURPOSE: To determine the level of hepatocyte growth factor (HGF) in the aqueous
      humor of patients with retinitis pigmentosa (RP). METHODS: This was a
      prospective, comparative control study. Aqueous humor samples were collected from
      the eyes of 15 RP patients. The level of HGF was determined with a commercially
      available enzyme-linked immunoabsorbent assay kit. The control group was composed
      of aqueous samples from 15 patients about to undergo cataract surgery with no
      other ocular or systemic diseases. RESULTS: The concentration of HGF was markedly
      higher in the aqueous humor of the patients with RP than in that of the control
      subjects (Mann-Whitney U test, P < 0.001). The level of HGF was 958.75 +/- 271.52
      (mean +/- SD) pg/mL in the eyes of the RP patients and 403.52 +/- 116.27 pg/mL in
      eyes of the control group. CONCLUSIONS: The concentration of HGF in aqueous humor
      is higher among patients with RP than in non-RP subjects. This finding provides
      new evidence that should be taken in account when considering HGF as a
      neuroprotective treatment for patients with RP.

PMID- 20053977
TI  - Patient preferences for diabetic retinopathy health States.
AB  - PURPOSE. To develop standardized descriptions of health states that characterize
      vision-specific functional impacts of diabetic retinopathy (DR) according to
      levels of visual acuity and contrast sensitivity and to elicit preferences for
      these health states from persons with DR and assign weighted values to them.
      METHODS. Vision-specific descriptions of health states were developed based on a
      literature review and patient and physician interviews. The content was based on
      items from the National Eye Institute Visual Functioning Questionnaire (VFQ) and
      reflected functional impacts experienced by DR patients. Values were assigned to
      the range of health states, anchored by the extremes full vision and death, by
      using the time-tradeoff method in a sample of 98 Canadian DR patients from three
      clinical centers. RESULTS. The mean age of the sample was 60.4 years, and 56%
      were men. Mean preferences decreased from 0.98 (better-eye logMAR [Snellen
      equivalent] acuity, > or =20/40; worse-eye Snellen equivalent, > or =20/200) to
      0.67 (Snellen equivalent visual acuity, < or =20/200, contrast sensitivity, < or
      =21 letters bilaterally). Preferences decreased with increasing severity of
      functional deficits and did not vary significantly by sex, age, VFQ quartile, or
      better- or worse-eye acuity. CONCLUSIONS. This is the first study that has been
      conducted to estimate preferences for standardized DR-specific health states,
      accounting for visual acuity and contrast sensitivity in both eyes. The results
      showed that the development and progression of DR are associated with substantial
      declines in preferences. In addition to the progressively greater impact from
      declining ETDRS visual acuity and contrast sensitivity, preference weights
      declined with increasing bilateral disparity. These preference values are useful
      for comparing the cost effectiveness of ophthalmic treatments.

PMID- 20053978
TI  - Monoscopic versus stereoscopic retinal photography for grading diabetic
      retinopathy severity.
AB  - PURPOSE: To assess agreement between monoscopic and stereoscopic photography for
      research classification of the severity of diabetic retinopathy (DR). METHODS:
      Monoscopic digital (MD) images were compared with stereo digital (SD) and film
      (SF) photographs from a 152-eye cohort with full-spectrum Early Treatment
      Diabetic Retinopathy Study (ETDRS) severity levels for agreement on severity
      level, DR presence with ascending severity threshold, presence of DR index
      lesions, and repeatability of grading. RESULTS: There was substantial agreement
      classifying ETDRS DR severity levels between MD and SF (kappa = 0.65, kappa(w)
      [linear weighted] = 0.87), MD and SD (kappa = 0.66, kappa(w) = 0.87), and SD and
      SF (kappa = 0.62, kappa(w) = 0.86) images. Marginal homogeneity analyses found no
      significant difference between MD and SF images (P = 0.53, Bhapkar test). The
      kappa agreement between MD and SF ranged from 0.80 to 0.94 for the presence or
      absence of eight ascending DR severity thresholds. Repeatability between the
      readers of the MD images was equal to or better than that of the readers of SD or
      SF images. Severity threshold grading repeatability between readers was similar
      with the MD and SF images. The kappa agreement between MD and SF for identifying
      diabetic retinopathy lesions ranged from moderate to almost perfect. The kappa
      comparisons showed that performance of grading new vessels on the disc in MD
      images was slightly lower than that with the SF images. CONCLUSIONS: Monoscopic
      photography can equal the reliability of stereo photography for full ETDRS DR
      severity scale grading.

PMID- 20053976
TI  - Responses of cultured human keratocytes and myofibroblasts to ethyl pyruvate: a
      microarray analysis of gene expression.
AB  - PURPOSE: Ethyl pyruvate (EP) has pharmacologic effects that remediate cellular
      stress. In the organ-cultured murine lens, EP ameliorates oxidative stress, and
      in a rat cataract model, it attenuates cataract formation. However, corneal
      responses to EP have not been elucidated. In this study, the potential of EP as a
      therapeutic agent in corneal wound healing was determined by examining its
      effects on the transition of quiescent corneal stromal keratocytes into
      contractile myofibroblasts. METHODS: Three independent preparations of cultured
      human keratocytes were treated with TGF-beta1, to elicit a phenotypic transition
      to myofibroblasts in the presence or absence of 10 or 15 mM EP. Gene expression
      profiles of the 12 samples (keratocytes +/- EP +/- TGF-beta1 for three
      preparations) were produced by using gene microarrays. RESULTS: TGF-beta1-driven
      twofold changes in at least two of three experiments defined a group of 1961
      genes. Genes showing twofold modulation by EP in at least two experiments
      appeared exclusively in myofibroblasts (857 genes), exclusively in keratocytes
      (409 genes), or in both phenotypes (252 genes). Analysis of these three EP
      modulated groups showed that EP (1) inhibited myofibroblast proliferation with
      concomitant modulation of some cell cycle genes, (2) augmented the NRF2-mediated
      antioxidant response in both keratocytes and myofibroblasts, and (3) modified the
      TGF-beta1-driven transition of keratocytes to myofibroblasts by inhibiting the
      upregulation of a subset of profibrotic genes. CONCLUSIONS: These EP-induced
      phenotypic changes in myofibroblasts indicate the potential of EP as a
      therapeutic agent in corneal wound healing.

PMID- 20053979
TI  - Molecular and biochemical characterization of folate transport proteins in
      retinal Muller cells.
AB  - PURPOSE: To analyze the mechanisms of folate uptake in retinal Muller cells.
      METHODS: RT-PCR and Western blot analysis were performed in freshly isolated
      neural retina and RPE/eyecup, primary mouse Muller cells, and rMC-1 cells for the
      three known folate transport proteins folate receptor alpha (FRalpha), proton
      coupled folate transporter (PCFT), and reduced folate carrier (RFC). Laser
      scanning confocal microscopy (LSCM) and immunoelectron microscopy were used to
      determine the subcellular location of FRalpha and PCFT in primary Muller cells.
      The pH dependence of the uptake of [(3)H]-methyltetrahydrofolate ([(3)H]-MTF) was
      assayed in Muller cells in the presence/absence of thiamine pyrophosphate, an
      inhibitor of RFC. RESULTS: FRalpha and PCFT are expressed abundantly in the
      retina in several cell layers, including the inner nuclear layer; they are
      present in primary mouse Muller cells and rMC-1 cells. LSCM localized these
      proteins to the plasma membrane, nuclear membrane, and perinuclear region.
      Immunoelectron microscopic studies revealed the colocalization of FRalpha and
      PCFT on the plasma membrane and nuclear membrane and within endosomal structures.
      Muller cell uptake of [(3)H]-MTF was robust at pH 5.0 to 6.0, consistent with
      PCFT activity, but also at neutral pH, reflecting RFC function. RFC was expressed
      in mouse Muller cells that had been allowed to proliferate in culture, but not in
      freshly isolated primary cells. CONCLUSIONS: FRalpha and PCFT are expressed in
      retinal Muller cells and colocalize in the endosomal compartment, suggesting that
      the two proteins may work coordinately to mediate folate uptake. The unexpected
      finding of RFC expression and activity in cultured Muller cells may reflect the
      upregulation of this protein under proliferative conditions.

PMID- 20053980
TI  - Modulation of inflammatory markers by miR-146a during replicative senescence in
      trabecular meshwork cells.
AB  - PURPOSE: To investigate the alterations in microRNA (miRNA) expression during
      replicative senescence (RS) in human trabecular meshwork (HTM) cells. METHODS:
      Two HTM cell lines were serially passaged until they reached RS. Changes in
      expression of 30 miRNAs were assessed by real-time quantitative (q)-PCR. The
      effects of miR-146a on gene expression were analyzed with gene arrays and the
      results confirmed by real-time q-PCR. Protein levels of IRAK1 and PAI-1 were
      analyzed by Western blot and those of IL6 and IL8 by ELISA. Senescence-associated
      markers were monitored by flow cytometry and cell proliferation by BrdU
      incorporation. RESULTS: RS of HTM cells was associated with significant changes
      in expression of 18 miRNAs, including the upregulation of miR-146a. miR-146a
      downregulated multiple genes associated with inflammation, including IRAK1, IL6,
      IL8, and PAI-1, inhibited senescence-associated beta-galactosidase (SA-beta-gal)
      activity and production of intracellular reactive species (iROS), and increased
      cell proliferation. Overexpression of either IRAK1 or PAI-1 inhibited the effects
      of miR-146a on cell proliferation and iROS production in senescent cells.
      CONCLUSIONS: RS in HTM cells was associated with changes in miRNA expression that
      could influence the senescent phenotype. Upregulation of the anti-inflammatory
      miR-146a may serve to restrain excessive production of inflammatory mediators in
      senescent cells and limit their deleterious effects on the surrounding tissue.
      Among the different proteins repressed by miR-146a, the inhibition of PAI-1 may
      act to minimize the effects of senescence on the generation of iROS and growth
      arrest and prevent alterations of the extracellular proteolytic activity of the
      TM.

PMID- 20053981
TI  - An evaluation of the Amblyopia and Strabismus Questionnaire using Rasch analysis.
AB  - PURPOSE: To evaluate whether the Amblyopia and Strabismus Questionnaire (A&SQ) is
      a suitable instrument for the assessment of vision-related quality-of life (VR
      QoL) in individuals with strabismus and/or amblyopia. METHODS: The A&SQ was
      completed by 102 individuals, all of whom had amblyopia, strabismus, or both.
      Rasch analysis was used to evaluate the usefulness of individual questionnaire
      items (i.e., questions); the response-scale performance; how well the items
      targeted VR-QoL; whether individual items showed response bias, depending on
      factors such as whether strabismus was present; and dimensionality. RESULTS:
      Items relating to concerns about the appearance of the eyes were applicable only
      to those with strabismus, and many items showed large ceiling effects. The
      response scale showed disordered responses and underused response options, which
      improved after the number of response options was reduced from five to three.
      This change improved the discriminative ability of the questionnaire (person
      separation index increased from 1.98 to 2.11). Significant bias was found between
      strabismic and nonstrabismic respondents. Separate Rasch analyses conducted for
      subjects with and without strabismus indicated that all A&SQ items seemed
      appropriate for individuals with strabismus (Rasch infit values between 0.60 and
      1.40), but several items fitted the model poorly in amblyopes without strabismus.
      The AS&Q was not found to be unidimensional. CONCLUSIONS: The findings highlight
      the limitations of the A&SQ instrument in the assessment of VR-QoL in subjects
      with strabismus and especially in those with amblyopia alone. The results suggest
      that separate instruments are needed to quantify VR-QoL in amblyopes with and
      without strabismus.

PMID- 20053982
TI  - Impact of tumor-associated macrophages in LH(BETA)T(AG) mice on retinal tumor
      progression: relation to macrophage subtype.
AB  - PURPOSE: To determine the distribution of tumor-associated macrophages (TAMs)
      during retinoblastoma tumor development, examine the contribution of bone marrow
      derived TAMs in retinoblastoma tumors, and evaluate the supportive role of TAMs
      in tumor growth in a transgenic retinoblastoma mouse model. METHODS: The time
      course of macrophage infiltration in transgenic retinoblastoma tumors was
      assessed by immunohistochemistry at different time points in tumorigenesis. The
      origin of TAMs in transgenic retinoblastoma tumors was determined by
      transplanting 10(7) bone marrow cells from green fluorescent protein (GFP)
      positive 16-week-old mice into age-matched, irradiated LH(BETA)T(AG) mice via
      tail vein injections. Macrophage depletion was performed by subconjunctival (SC)
      delivery of liposomal clodronate. RESULTS: The density of TAMs increased from 4
      to 12 weeks of age in mice with small to medium tumors (P = 0.037) and remained
      stable in the later stages of disease (i.e., 16 weeks old with large tumors; P =
      0.20). In 16-week-old mice, 38% (2.5 +/- 3.2 cells per 400x high-power field) of
      TAMs were GFP-positive, bone marrow-derived macrophages. Total TAM depletion was
      associated with a significant decrease in the expression levels of MMP-9 (P =
      0.014) and mature vessels (P < 0.001) and a nonsignificant decrease in the
      density of neovessels (P = 0.94). The density of M2-polarized TAMs did not change
      significantly after TAM depletion (P = 0.68). After M1-polarized TAM depletion,
      the tumor burden increased (P = 0.056). CONCLUSIONS: This work extends
      understanding of the complex role that macrophages play in retinoblastoma.
      Macrophage modulation in the tumor microenvironment is a critical factor in
      retinoblastoma tumor progression.

PMID- 20053983
TI  - Antifibrotic effect of Pirfenidone on orbital fibroblasts of patients with
      thyroid-associated ophthalmopathy by decreasing TIMP-1 and collagen levels.
AB  - PURPOSE: The aim of this study was to determine the antifibrotic effects of
      pirfenidone in orbital fibroblasts of patients with thyroid-associated
      ophthalmopathy (TAO). METHODS: The effects of interleukin (IL)-1beta and of
      fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), and
      transforming growth factor (TGF)-beta on the induction of tissue inhibitors of
      metalloproteinases (TIMP)-1 were assessed in orbital fibroblasts of TAO patients.
      TIMP-1 protein levels were measured by ELISA and Western blot analyses, and TIMP
      1 activity was assessed by reverse zymography. The effect of pirfenidone on TIMP
      1 induction in orbital fibroblasts was evaluated with the same methods using
      dexamethasone as a reference agent. A hydroxyproline assay was used to determine
      the effect of pirfenidone and dexamethasone on collagen production in orbital
      fibroblasts, and the tetrazolium-based MTT assay was used to assess pirfenidone
      cytotoxicity. RESULTS: IL-1beta strongly and dose dependently increased the level
      of active TIMP-1 protein, whereas FGF, PDGF, and TGF-beta did not significantly
      induce TIMP-1 protein. Pirfenidone was more effective than dexamethasone in
      inhibiting IL-1beta-induced increases in TIMP-1, reducing TIMP-1 levels to less
      than those in untreated controls at a minimal concentration (5 mM). Moreover,
      pirfenidone effectively decreased hydroxyproline levels in orbital fibroblasts,
      whereas dexamethasone had no effect on hydroxyproline levels. Pirfenidone
      exhibited no toxicity in orbital fibroblasts at the concentrations used.
      CONCLUSIONS: These results indicate that nontoxic concentrations of pirfenidone
      have significant antifibrotic effects on orbital fibroblasts from patients with
      TAO.

PMID- 20053984
TI  - Flexible recognition of the tRNA G18 methylation target site by TrmH
      methyltransferase through first binding and induced fit processes.
AB  - Transfer RNA (Gm18) methyltransferase (TrmH) catalyzes methyl transfer from S
      adenosyl-l-methionine to a conserved G18 in tRNA. We investigated the recognition
      mechanism of Thermus thermophilus TrmH for its guanosine target. Thirteen yeast
      tRNA(Phe) mutant transcripts were prepared in which the modification site and/or
      other nucleotides in the D-loop were substituted by dG, inosine, or other
      nucleotides. We then conducted methyl transfer kinetic studies, gel shift assays,
      and inhibition experiments using these tRNA variants. Sites of methylation were
      confirmed with RNA sequencing or primer extension. Although the G18G19 sequence
      is not essential for methylation by TrmH, disruption of G18G19 severely reduces
      the efficiency of methyl transfer. There is strict recognition of guanosine by
      TrmH, in that methylation occurs at the adjacent G19 when the G18 is replaced by
      dG or adenosine. The fact that TrmH methylates guanosine in D-loops from 4 to 12
      nucleotides in length suggests that selection of the position of guanosine within
      the D-loop is relatively flexible. Our studies also demonstrate that the oxygen 6
      atom of the guanine base is a positive determinant for TrmH recognition. The
      recognition process of TrmH for substrate is inducible and product-inhibited, in
      that tRNAs containing Gm18 are excluded by TrmH. In contrast, substitution of G18
      with dG18 results in the formation of a more stable TrmH-tRNA complex. To address
      the mechanism, we performed the stopped-flow pre-steady state kinetic analysis.
      The result clearly showed that the binding of TrmH to tRNA is composed of at
      least three steps, the first bi-molecular binding and the subsequent two uni
      molecular induced-fit processes.

PMID- 20053985
TI  - Hsp70 interacts with the retroviral restriction factor TRIM5alpha and assists the
      folding of TRIM5alpha.
AB  - Tripartite motif (TRIM) protein TRIM5alpha has been shown to restrict human
      immunodeficiency virus, type 1 infection in Old World monkey cells at the early
      post-entry step by poorly understood mechanisms. Currently, the physiological
      function of TRIM5alpha is not known. In this study, we showed that transiently
      overexpressed TRIM5alpha causes a morphological change in HEK293T cells. A
      proteomics analysis of the protein complexes that were pulled down with
      hemagglutinin-tagged TRIM5alpha suggested that the heat shock protein 70 (Hsp70)
      may serve as a TRIM5alpha-binding partner. The interaction between Hsp70 and
      TRIM5alpha was confirmed by co-localization and co-immunoprecipitation assays. Co
      expression of Hsp70 reversed the TRIM5alpha-induced morphological change in
      HEK293T cells. Another heat shock protein Hsc70 also bound to TRIM5alpha, but
      unlike Hsp70, Hsc70 was not able to reverse the TRIM5alpha-induced morphological
      change, suggesting that Hsp70 specifically reverses the morphological change
      caused by TRIM5alpha. Studies using a series of TRIM5alpha deletion mutants
      demonstrate that, although the PRYSPRY domain is critical for binding to Hsp70,
      the entire TRIM5alpha structure is necessary to induce the morphological change
      of cells. When the ATPase domain of Hsp70 was mutated, the mutated Hsp70 could
      not counteract the morphological change induced by TRIM5alpha, indicating that
      the catalytic activity of Hsp70 protein is important for this function. Co
      expression of Hsp70 elevated the levels of TRIM5alpha in the detergent-soluble
      fraction with a concomitant decrease in the detergent-insoluble fraction.
      Together these results suggest that Hsp70 plays critical roles in the cellular
      management against the TRIM5alpha-induced cellular insults.

PMID- 20053986
TI  - Heterodimerization with different Jun proteins controls c-Fos intranuclear
      dynamics and distribution.
AB  - The c-Fos proto-oncogenic transcription factor defines a multigene family
      controlling many processes both at the cell and the whole organism level. To bind
      to its target AP-1/12-O-tetradecanoylphorbol-13-acetate-responsive element or
      cAMP-responsive element DNA sequences in gene promoters and exert its
      transcriptional part, c-Fos must heterodimerize with other bZip proteins, its
      best studied partners being the Jun proteins (c-Jun, JunB, and JunD). c-Fos
      expression is regulated at many transcriptional and post-transcriptional levels,
      yet little is known on how its localization is dynamically regulated in the cell.
      Here we have investigated its intranuclear mobility using fluorescence recovery
      after photobleaching, genetic, and biochemical approaches. Whereas monomeric c
      Fos is highly mobile and distributed evenly with nucleolar exclusion in the
      nucleus, heterodimerization with c-Jun entails intranuclear redistribution and
      dramatic reduction in mobility of c-Fos caused by predominant association with
      the nuclear matrix independently of any binding to AP-1/12-O-tetradecanoylphorbol
      13-acetate-responsive element or cAMP-responsive element sequences. In contrast
      to c-Jun, dimerization with JunB does not detectably affect c-Fos mobility.
      However, dimerization with JunB affects intranuclear distribution with
      significant differences in the localization of c-Fos.c-Jun and c-Fos.JunB dimers.
      Moreover, c-Jun and JunB exert comparable effects on another Fos family member,
      Fra-1. Thus, we report a novel regulation, i.e. differentially regulated
      intranuclear mobility and distribution of Fos proteins by their Jun partners, and
      suggest the existence of intranuclear storage sites for latent c-Fos.c-Jun AP-1
      complexes. This may affect the numerous physiopathological functions these
      transcription factors control.

PMID- 20053987
TI  - The transgenic overexpression of alpha-synuclein and not its related pathology
      associates with complex I inhibition.
AB  - Alpha-synuclein (alphaS) is a protein involved in the cytopathology and genetics
      of Parkinson disease and is thought to affect mitochondrial complex I activity.
      Previous studies have shown that mitochondrial toxins and specifically inhibitors
      of complex I activity enhance alphaS pathogenesis. Here we show that alphaS
      overexpression specifically inhibits complex I activity in dopaminergic cells and
      in A53T alphaS transgenic mouse brains. Importantly, our results indicate that
      the inhibitory effect on complex I activity is not associated with alphaS-related
      pathology. Specifically, complex I activity measured in purified mitochondria
      from A53T alphaS transgenic mouse brains was not affected by mouse age; Parkinson
      disease-like symptoms; levels of alphaS soluble oligomers; levels of insoluble,
      lipid-associated alphaS; or alphaS intraneuronal depositions in vivo. Likewise,
      no correlation was found between complex I activity and polyunsaturated fatty
      acid-induced alphaS depositions in Lewy body-like inclusions in cultured
      dopaminergic cells. We further show that the effect of alphaS on complex I
      activity is not due to altered mitochondrial protein levels or affected complex I
      assembly. Based on the results herein, we suggest that alphaS expression
      negatively regulates complex I activity as part of its normal, physiological
      role.

PMID- 20053988
TI  - A CD36-related transmembrane protein is coordinated with an intracellular lipid
      binding protein in selective carotenoid transport for cocoon coloration.
AB  - The transport pathway of specific dietary carotenoids from the midgut lumen to
      the silk gland in the silkworm, Bombyx mori, is a model system for selective
      carotenoid transport because several genetic mutants with defects in parts of
      this pathway have been identified that manifest altered cocoon pigmentation. In
      the wild-type silkworm, which has both genes, Yellow blood (Y) and Yellow cocoon
      (C), lutein is transferred selectively from the hemolymph lipoprotein to the silk
      gland cells where it is accumulated into the cocoon. The Y gene encodes an
      intracellular carotenoid-binding protein (CBP) containing a lipid-binding domain
      known as the steroidogenic acute regulatory protein-related lipid transfer
      domain. Positional cloning and transgenic rescue experiments revealed that the C
      gene encodes Cameo2, a transmembrane protein gene belonging to the CD36 family
      genes, some of which, such as the mammalian SR-BI and the fruit fly ninaD, are
      reported as lipoprotein receptors or implicated in carotenoid transport for
      visual system. In C mutant larvae, Cameo2 expression was strongly repressed in
      the silk gland in a specific manner, resulting in colorless silk glands and white
      cocoons. The developmental profile of Cameo2 expression, CBP expression, and
      lutein pigmentation in the silk gland of the yellow cocoon strain were
      correlated. We hypothesize that selective delivery of lutein to specific tissue
      requires the combination of two components: 1) CBP as a carotenoid transporter in
      cytosol and 2) Cameo2 as a transmembrane receptor on the surface of the cells.

PMID- 20053989
TI  - A tyrosine-based motif localizes a Drosophila vesicular transporter to synaptic
      vesicles in vivo.
AB  - Vesicular neurotransmitter transporters must localize to synaptic vesicles (SVs)
      to allow regulated neurotransmitter release at the synapse. However, the signals
      required to localize vesicular proteins to SVs in vivo remain unclear. To address
      this question we have tested the effects of mutating proposed trafficking domains
      in Drosophila orthologs of the vesicular monoamine and glutamate transporters,
      DVMAT-A and DVGLUT. We show that a tyrosine-based motif (YXXY) is important both
      for DVMAT-A internalization from the cell surface in vitro, and localization to
      SVs in vivo. In contrast, DVGLUT deletion mutants that lack a putative C-terminal
      trafficking domain show more modest defects in both internalization in vitro and
      trafficking to SVs in vivo. Our data show for the first time that mutation of a
      specific trafficking motif can disrupt localization to SVs in vivo and suggest
      possible differences in the sorting of VMATs versus VGLUTs to SVs at the synapse.

PMID- 20053990
TI  - Protein crystallography reveals a role for the FS0 cluster of Escherichia coli
      nitrate reductase A (NarGHI) in enzyme maturation.
AB  - We have used site-directed mutagenesis, EPR spectroscopy, redox potentiometry,
      and protein crystallography to monitor assembly of the FS0 [4Fe-4S] cluster and
      molybdo-bis(pyranopterin guanine dinucleotide) cofactor (Mo-bisPGD) of the
      Escherichia coli nitrate reductase A (NarGHI) catalytic subunit (NarG). Cys and
      Ser mutants of NarG-His(49) both lack catalytic activity, with only the former
      assembling FS0 and Mo-bisPGD. Importantly, both prosthetic groups are absent in
      the NarG-H49S mutant. EPR spectroscopy of the Cys mutant reveals that the E(m)
      value of the FS0 cluster is decreased by at least 500 mV, preventing its
      participation in electron transfer to the Mo-bisPGD cofactor. To demonstrate that
      decreasing the FS0 cluster E(m) results in decreased enzyme activity, we mutated
      a critical Arg residue (NarG-Arg(94)) in the vicinity of FS0 to a Ser residue. In
      this case, the E(m) of FS0 is decreased by 115 mV, with a concomitant decrease in
      enzyme turnover to approximately 30% of the wild type. Analysis of the structure
      of the NarG-H49S mutant reveals two important aspects of NarGHI maturation: (i)
      apomolybdo-NarGHI is able to bind GDP moieties at their respective P and Q sites
      in the absence of the Mo-bisPGD cofactor, and (ii) a critical segment of residues
      in NarG, (49)HGVNCTG(55), must be correctly positioned to ensure holoenzyme
      maturation.

PMID- 20053991
TI  - A pivot between helices V and VI near the retinal-binding site is necessary for
      activation in rhodopsins.
AB  - Rhodopsins are photoreceptor proteins that have diverged from ligand-binding G
      protein-coupled receptors (GPCRs). Unlike other GPCRs, rhodopsins contain an
      intrinsic antagonist, 11-cis-retinal, which is converted to the agonist all-trans
      retinal upon absorption of a photon. Through evolution, vertebrate rhodopsins
      have lost the ability of direct binding to the agonist, but some invertebrate and
      vertebrate non-visual rhodopsins have retained this ability. Here, we
      investigated the difference in the agonist-binding state between these rhodopsins
      to further our understanding of the structural and functional diversity of
      rhodopsins. Mutational analyses of agonist-binding rhodopsin showed that
      replacement of Ala-269, one of the residues constituting the antagonist-binding
      site, with bulky amino acids resulted in a large spectral shift in its active
      state and a great reduction in G protein activity, whereas these were rescued by
      subsequent replacement of Phe-208 with smaller amino acids. Although similar
      replacements in vertebrate rhodopsin did not cause a spectral shift in the active
      state, a similar reduction in and recovery of G protein activity was observed.
      Therefore, the agonist is located close to Ala-269 in the agonist-binding
      rhodopsin, but not in vertebrate rhodopsins, and Ala-269 with Phe-208 acts as a
      pivot for the formation of the G protein-activating state in both rhodopsins. The
      positions corresponding to Ala-269 and Phe-208 in other GPCRs have been reported
      to form part of an agonist-binding site. Therefore, an agonist-binding rhodopsin
      has the molecular architecture of the agonist-binding site similar to that of a
      general GPCR, whereas vertebrate rhodopsins changed the architecture, resulting
      in loss of agonist binding during molecular evolution.

PMID- 20053992
TI  - Sucrose octasulfate selectively accelerates thrombin inactivation by heparin
      cofactor II.
AB  - Inactivation of thrombin (T) by the serpins heparin cofactor II (HCII) and
      antithrombin (AT) is accelerated by a heparin template between the serpin and
      thrombin exosite II. Unlike AT, HCII also uses an allosteric interaction of its
      NH(2)-terminal segment with exosite I. Sucrose octasulfate (SOS) accelerated
      thrombin inactivation by HCII but not AT by 2000-fold. SOS bound to two sites on
      thrombin, with dissociation constants (K(D)) of 10 +/- 4 microm and 400 +/- 300
      microm that were not kinetically resolvable, as evidenced by single hyperbolic
      SOS concentration dependences of the inactivation rate (k(obs)). SOS bound HCII
      with K(D) 1.45 +/- 0.30 mm, and this binding was tightened in the T.SOS.HCII
      complex, characterized by K(complex) of approximately 0.20 microm. Inactivation
      data were incompatible with a model solely depending on HCII.SOS but fit an
      equilibrium linkage model employing T.SOS binding in the pathway to higher order
      complex formation. Hirudin-(54-65)(SO(3)(-)) caused a hyperbolic decrease of the
      inactivation rates, suggesting partial competitive binding of hirudin-(54
      65)(SO(3)(-)) and HCII to exosite I. Meizothrombin(des-fragment 1), binding SOS
      with K(D) = 1600 +/- 300 microm, and thrombin were inactivated at comparable
      rates, and an exosite II aptamer had no effect on the inactivation, suggesting
      limited exosite II involvement. SOS accelerated inactivation of meizothrombin
      1000-fold, reflecting the contribution of direct exosite I interaction with HCII.
      Thrombin generation in plasma was suppressed by SOS, both in HCII-dependent and 
      independent processes. The ex vivo HCII-dependent process may utilize the
      proposed model and suggests a potential for oversulfated disaccharides in
      controlling HCII-regulated thrombin generation.

PMID- 20053993
TI  - c-Jun induces mammary epithelial cellular invasion and breast cancer stem cell
      expansion.
AB  - The molecular mechanisms governing breast tumor cellular self-renewal contribute
      to breast cancer progression and therapeutic resistance. The ErbB2 oncogene is
      overexpressed in approximately 30% of human breast cancers. c-Jun, the first
      cellular proto-oncogene, is overexpressed in human breast cancer. However, the
      role of endogenous c-Jun in mammary tumor progression is unknown. Herein,
      transgenic mice expressing the mammary gland-targeted ErbB2 oncogene were crossed
      with c-jun(f/f) transgenic mice to determine the role of endogenous c-Jun in
      mammary tumor invasion and stem cell function. The excision of c-jun by Cre
      recombinase reduced cellular migration, invasion, and mammosphere formation of
      ErbB2-induced mammary tumors. Proteomic analysis identified a subset of secreted
      proteins (stem cell factor (SCF) and CCL5) induced by ErbB2 expression that were
      dependent upon endogenous c-Jun expression. SCF and CCL5 were identified as
      transcriptionally induced by c-Jun. CCL5 rescued the c-Jun-deficient breast tumor
      cellular invasion phenotype. SCF rescued the c-Jun-deficient mammosphere
      production. Endogenous c-Jun thus contributes to ErbB2-induced mammary tumor cell
      invasion and self-renewal.

PMID- 20053994
TI  - Crystal structure of the Mp1p ligand binding domain 2 reveals its function as a
      fatty acid-binding protein.
AB  - Penicillium marneffei is a dimorphic, pathogenic fungus in Southeast Asia that
      mostly afflicts immunocompromised individuals. As the only dimorphic member of
      the genus, it goes through a phase transition from a mold to yeast form, which is
      believed to be a requisite for its pathogenicity. Mp1p, a cell wall antigenic
      mannoprotein existing widely in yeast, hyphae, and conidia of the fungus, plays a
      vital role in host immune response during infection. To understand the function
      of Mp1p, we have determined the x-ray crystal structure of its ligand binding
      domain 2 (LBD2) to 1.3 A. The structure reveals a dimer between the two
      molecules. The dimer interface forms a ligand binding cavity, in which electron
      density was observed for a palmitic acid molecule interacting with LBD2
      indirectly through hydrogen bonding networks via two structural water molecules.
      Isothermal titration calorimetry experiments measured the ligand binding affinity
      (K(d)) of Mp1p at the micromolar level. Mutations of ligand-binding residues,
      namely S313A and S332A, resulted in a 9-fold suppression of ligand binding
      affinity. Analytical ultracentrifugation assays demonstrated that both LBD2 and
      Mp1p are mostly monomeric in vitro, no matter with or without ligand, and our
      dimeric crystal structure of LBD2 might be the result of crystal packing. Based
      on the conformation of the ligand-binding pocket in the dimer structure, a model
      for the closed, monomeric form of LBD2 is proposed. Further structural analysis
      indicated the biological importance of fatty acid binding of Mp1p for the
      survival and pathogenicity of the conditional pathogen.

PMID- 20053995
TI  - Crystal structure of an affinity-matured prolactin complexed to its dimerized
      receptor reveals the topology of hormone binding site 2.
AB  - We report the first crystal structure of a 1:2 hormone.receptor complex that
      involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary
      complexes were obtained by generating affinity-matured PRL variants harboring an
      N-terminal tail from ovine placental lactogen, a closely related PRL receptor
      (PRLR) ligand. This structure allows one to draw up an exhaustive inventory of
      the residues involved at the PRL.PRLR site 2 interface, consistent with all
      previously reported site-directed mutagenesis data. We propose, with this
      description, an interaction model involving three structural components of PRL
      site 2 ("three-pin plug"): the conserved glycine 129 of helix alpha3, the
      hydrogen bond network involving surrounding residues (glycine cavity), and the N
      terminus. The model provides a molecular basis for the properties of the
      different PRL analogs designed to date, including PRLR antagonists. Finally,
      comparison of our 1:2 PRL.PRLR(2) structure with those of free PRL and its 1:1
      complex indicates that the structure of PRL undergoes significant changes when
      binding the first, but not the second receptor. This suggests that the second
      PRLR moiety adapts to the 1:1 complex rather than the opposite. In conclusion,
      this structure will be a useful guiding tool for further investigations of the
      molecular mechanisms involved in PRLR dimerization and activation, as well as for
      the optimization of PRLR antagonists, an emerging class of compounds with high
      therapeutic potential against breast and prostate cancer.

PMID- 20053996
TI  - A novel mannose-binding lectin/ficolin-associated protein is highly expressed in
      heart and skeletal muscle tissues and inhibits complement activation.
AB  - The human lectin complement pathway involves circulating complexes consisting of
      mannose-binding lectin (MBL) or three ficolins (ficolin-1, -2, and -3) in
      association with three MBL/ficolin-associated serine proteases (MASP) (MASP-1, 
      2, and -3) and a nonenzymatic sMAP. MASP-1 and MASP-3 (MASP1 isoforms 1 and 2,
      respectively) are splice variants of the MASP1 gene, whereas MASP-2 and sMAP are
      splice variants of the MASP2 gene. We have identified a novel serum protein of 45
      kDa that is associated with MBL and the ficolins. This protein is named
      MBL/ficolin-associated protein 1 (MAP-1 corresponding to MASP1 isoform 3). The
      transcript generating MAP-1 (MASP1_v3) contains exons 1-8 and a novel exon
      encoding an in-frame stop codon. The corresponding protein lacks the serine
      protease domains but contains most of the common heavy chain of MASP-1 and MASP
      3. Additionally MAP-1 contains 17 unique C-terminal amino acids. By use of
      quantitative PCR and MAP-1-specific immunohistochemistry, we found that MAP-1 is
      highly expressed in myocardial and skeletal muscle tissues as well as in liver
      hepatocytes with a different expression profile than that observed for MASP-1 and
      MASP-3. MAP-1 co-precipitated from human serum with MBL, ficolin-2, and ficolin
      3, and recombinant MAP-1 was able to inhibit complement C4 deposition via both
      the ficolin-3 and MBL pathway. In conclusion we have identified a novel 45-kDa
      serum protein derived from the MASP1 gene, which is highly expressed in striated
      muscle tissues. It is found in complex with MBL and ficolins and may function as
      a potent inhibitor of the complement system in vivo.

PMID- 20053997
TI  - Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl
      hydrocarbon receptor in the regulation of the human phase II detoxifying UDP
      glucuronosyltransferase 1A10.
AB  - The defense against oxidative stress is a critical feature that prevents cellular
      and DNA damage. UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation
      of xenobiotics, mutagens, and reactive metabolites and thus act as indirect
      antioxidants. Aim of this study was to elucidate the regulation of UGTs expressed
      in the mucosa of the gastrointestinal tract by xenobiotics and the main mediator
      of antioxidant defense, Nrf2 (nuclear factor erythroid 2-related factor 2).
      Xenobiotic (XRE) and antioxidant (ARE) response elements were detected in the
      promoters of UGT1A8, UGT1A9, and UGT1A10. Reporter gene experiments demonstrated
      XRE-mediated induction by dioxin in addition to tert-butylhydroquinone (ARE)
      mediated induction of UGT1A8 and UGT1A10, which are expressed in extrahepatic
      tissue in humans in vivo. The responsible XRE and ARE motifs were identified by
      mutagenesis. Small interfering RNA knockdown, electrophoretic mobility shifts,
      and supershifts identified a functional interaction of Nrf2 and the aryl
      hydrocarbon receptor (AhR). Induction of UGT1A8 and UGT1A10 requires Nrf2 and
      AhR. It proceeds by utilizing XRE- as well as ARE-binding motifs. In summary, we
      demonstrate the coordinated AhR- and Nrf2-dependent transcriptional regulation of
      human UGT1As. Cellular protection by glucuronidation is thus inducible by
      xenobiotics via AhR and by oxidative metabolites via Nrf2 linking glucuronidation
      to cellular protection and defense against oxidative stress.

PMID- 20053998
TI  - p38 regulates pigmentation via proteasomal degradation of tyrosinase.
AB  - The synthesis of melanin pigments, or melanogenesis, is regulated by the balance
      of a variety of signal transduction pathways. Among these pathways, p38 MAPK
      signaling was found to be involved in stress-induced melanogenesis and to be
      activated by alpha-melanocyte-stimulating hormone (alpha-MSH) and ultraviolet
      irradiation. Previous studies have shown that alpha-MSH-stimulated melanogenesis
      can be inhibited by blocking p38 MAPK activity with SB203580, a pyridinyl
      imidazole compound. Consistent with this, we observed that pyridinyl imidazoles
      (SB203580 and SB202190) inhibited both basal and alpha-MSH-induced melanogenesis
      in B16 melanoma cells. However, SB202474, which has no ability to inhibit p38
      MAPK activity and is usually used as a negative control compound in p38 MAPK
      studies, also suppressed melanin synthesis induction. Furthermore, the
      independence of the p38 kinase pathway from the repression of melanogenesis by
      pyridinyl imidazole compounds was also confirmed by small interfering RNA
      experiments. Interfering with p38 MAPK expression surprisingly stimulated
      melanogenesis and tyrosinase family protein expression. Although the molecular
      mechanism(s) by which p38 promotes the degradation of melanogenic enzymes remain
      to be determined, the involvement of the ubiquitin-proteasome pathway was
      demonstrated by co-treatment with the proteasome-specific inhibitor MG132 and the
      relative decrease in the ubiquitination of tyrosinase in cells transfected with
      p38-specific small interfering RNA.

PMID- 20053999
TI  - Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus
      (Linnaeus, 1758) safely inhibits arterial thrombosis after photochemically
      induced endothelial lesion.
AB  - Heparin-like glycans with diverse disaccharide composition and high anticoagulant
      activity have been described in several families of marine mollusks. The present
      work focused on the structural characterization of a new heparan sulfate (HS)
      like polymer isolated from the mollusk Nodipecten nodosus (Linnaeus, 1758) and on
      its anticoagulant and antithrombotic properties. Total glycans were extracted
      from the mollusk and fractionated by ethanol precipitation. The main component
      (>90%) was identified as HS-like glycosaminoglycan, representing approximately
      4.6 mg g(-1) of dry tissue. The mollusk HS resists degradation with heparinase I
      but is cleaved by nitrous acid. Analysis of the mollusk glycan by one-dimensional
      (1)H, two-dimensional correlated spectroscopy, and heteronuclear single quantum
      coherence nuclear magnetic resonance revealed characteristic signals of
      glucuronic acid and glucosamine residues. Signals corresponding to anomeric
      protons of nonsulfated, 3- or 2-sulfated glucuronic acid as well as N-sulfated
      and/or 6-sulfated glucosamine were also observed. The mollusk HS has an
      anticoagulant activity of 36 IU mg(-1), 5-fold lower than porcine heparin (180 IU
      mg(-1)), as measured by the activated partial thromboplastin time assay. It also
      inhibits factor Xa (IC(50) = 0.835 microg ml(-1)) and thrombin (IC(50) = 9.3
      microg ml(-1)) in the presence of antithrombin. In vivo assays demonstrated that
      at the dose of 1 mg kg(-1), the mollusk HS inhibited thrombus growth in
      photochemically injured arteries. No bleeding effect, factor XIIa-mediated
      kallikrein activity, or toxic effect on fibroblast cells was induced by the
      invertebrate HS at the antithrombotic dose.

PMID- 20054000
TI  - Akt Cys-310-targeted inhibition by hydroxylated benzene derivatives is tightly
      linked to their immunosuppressive effects.
AB  - The hydroxylated benzene metabolite hydroquinone (HQ) is mainly generated from
      benzene, an important industrial chemical, and is also a common dietary
      component. Although numerous reports have addressed the tumorigenesis-inducing
      effects of HQ, few papers have explored its molecular regulatory mechanism in
      immunological responses. In this study we characterized Akt (protein kinase B)
      targeted regulation by HQ and its derivatives, in suppressing inflammatory
      responses using cellular, molecular, biochemical, and immunopharmacological
      approaches. HQ down-regulated inflammatory responses such as NO production,
      surface levels of pattern recognition receptors, and cytokine gene expression
      with IC(50) values that ranged from 5 to 10 microm. HQ inhibition was mediated by
      blocking NF-kappaB activation via suppression of its translocation pathway, which
      is composed of Akt, I kappaB alpha kinase beta, and I kappaB alpha. Of the
      targets in this pathway, HQ directly targeted and bound to the sulfhydryl group
      of Cys-310 of Akt and sequentially interrupted the phosphorylation of both Thr
      308 and Ser-473 by mediation of beta-mercaptoethanol, according to the liquid
      chromatography/mass spectroscopy analysis of the interaction of HQ with an Akt
      derived peptide. Therefore, our data suggest that Akt and its target site Cys-310
      can be considered as a prime molecular target of HQ-mediated immunosuppression
      and for novel anti-Akt-targeted immunosuppressive drugs.

PMID- 20054001
TI  - NF-YC functions as a corepressor of agonist-bound mineralocorticoid receptor.
AB  - The role of aldosterone has been implicated in the metabolic syndrome and
      cardiovascular diseases. The biological actions of aldosterone are mediated
      through mineralocorticoid receptor (MR). Nuclear receptor-mediated gene
      expression is regulated by dynamic and coordinated recruitment of coactivators
      and corepressors. To identify new coregulators of the MR, full-length MR was used
      as bait in yeast two-hybrid screening. We isolated NF-YC, one of the subunits of
      heterotrimeric transcription factor NF-Y. Specific interaction between MR and NF
      YC was confirmed by yeast two-hybrid, mammalian two-hybrid, coimmunoprecipitation
      assays, and fluorescence subcellular imaging. Transient transfection experiments
      in COS-7 cells demonstrated that NF-YC repressed MR transactivation in a hormone
      sensitive manner. Moreover, reduction of NF-YC protein levels by small
      interfering RNA potentiated hormonal activation of endogenous target genes in
      stably MR-expressing cells, indicating that NF-YC functions as an agonist
      dependent MR corepressor. The corepressor function of NF-YC is selective for MR,
      because overexpression of NF-YC did not affect transcriptional activity mediated
      by androgen, progesterone, or glucocorticoid receptors. Chromatin
      immunoprecipitation experiments showed that endogenous MR and steroid receptor
      coactivator-1 were recruited to an endogenous ENaC gene promoter in a largely
      aldosterone-dependent manner, and endogenous NF-YC was sequentially recruited to
      the same element. Immunohistochemistry showed that endogenous MR and NF-YC were
      colocalized within the mouse kidney. Although aldosterone induces interaction of
      the N and C termini of MR, NF-YC inhibited the N/C interaction. These findings
      indicate that NF-YC functions as a new corepressor of agonist-bound MR via
      alteration of aldosterone-induced MR conformation.

PMID- 20054002
TI  - DIP2A functions as a FSTL1 receptor.
AB  - FSTL1 is an extracellular glycoprotein whose functional significance in
      physiological and pathological processes is incompletely understood. Recently, we
      have shown that FSTL1 acts as a muscle-derived secreted factor that is up
      regulated by Akt activation and ischemic stress and that FSTL1 exerts favorable
      actions on the heart and vasculature. Here, we sought to identify the receptor
      that mediates the cellular actions of FSTL1. We identified DIP2A as a novel FSTL1
      binding partner from the membrane fraction of endothelial cells. Co
      immunoprecipitation assays revealed a direct physical interaction between FSTL1
      and DIP2A. DIP2A was present on the cell surface of endothelial cells, and
      knockdown of DIP2A by small interfering RNA reduced the binding of FSTL1 to
      cells. In cultured endothelial cells, knockdown of DIP2A by small interfering RNA
      diminished FSTL1-stimulated survival, migration, and differentiation into network
      structures and inhibited FSTL1-induced Akt phosphorylation. In cultured cardiac
      myocytes, ablation of DIP2A reduced the protective actions of FSTL1 on
      hypoxia/reoxygenation-induced apoptosis and suppressed FSTL1-induced Akt
      phosphorylation. These data indicate that DIP2A functions as a novel receptor
      that mediates the cardiovascular protective effects of FSTL1.

PMID- 20054003
TI  - Inhibition of secretion of interleukin (IL)-12/IL-23 family cytokines by 4
      trifluoromethyl-celecoxib is coupled to degradation via the endoplasmic reticulum
      stress protein HERP.
AB  - Interleukin-12 (IL-12), p80, and IL-23 are structurally related cytokines sharing
      a p40 subunit. We have recently demonstrated that celecoxib and its COX-2
      independent analogue 4-trifluoromethyl-celecoxib (TFM-C) inhibit secretion but
      not transcription of IL-12 (p35/p40) and p80 (p40/p40). This is associated with a
      mechanism involving altered cytokine-chaperone interaction in the endoplasmic
      reticulum (ER). In the present study, we found that celecoxib and TFM-C also
      block secretion of IL-23 (p40/p19 heterodimers). Given the putative ER-centric
      mode of these compounds, we performed a comprehensive RT-PCR analysis of 23 ER
      resident chaperones/foldases and associated co-factors. This revealed that TFM-C
      induced 1.5-3-fold transcriptional up-regulation of calreticulin, GRP78, GRP94,
      GRP170, ERp72, ERp57, ERdj4, and ERp29. However, more significantly, a 7-fold up
      regulation of homocysteine-inducible ER protein (HERP) was observed. HERP is part
      of a high molecular mass protein complex involved in ER-associated protein
      degradation (ERAD). Using co-immunoprecipitation assays, we show that TFM-C
      induces protein interaction of p80 and IL-23 with HERP. Both HERP siRNA knockdown
      and HERP overexpression coupled to cycloheximide chase assays revealed that HERP
      is necessary for degradation of intracellularly retained p80 by TFM-C. Thus, our
      data suggest that targeting cytokine folding in the ER by small molecule drugs
      could be therapeutically exploited to alleviate inappropriate inflammation in
      autoimmune conditions.

PMID- 20054005
TI  - Brain, heal thyself! Neuroregeneration in the subventricular zone after ischemic
      stroke.

PMID- 20054004
TI  - Conformational changes induced in voltage-gated calcium channel Cav1.2 by BayK
      8644 or FPL64176 modify the kinetics of secretion independently of Ca2+ influx.
AB  - The role of the L-type calcium channel (Cav1.2) as a molecular switch that
      triggers secretion prior to Ca(2+) transport has previously been demonstrated in
      bovine chromaffin cells and rat pancreatic beta cells. Here, we examined the
      effect of specific Cav1.2 allosteric modulators, BayK 8644 (BayK) and FPL64176
      (FPL), on the kinetics of catecholamine release, as monitored by amperometry in
      single bovine chromaffin cells. We show that 2 microm BayK or 0.5 microm FPL
      accelerates the rate of catecholamine secretion to a similar extent in the
      presence either of the permeable Ca(2+) and Ba(2+) or the impermeable charge
      carrier La(3+). These results suggest that structural rearrangements generated
      through the binding of BayK or FPL, by altering the channel activity, could
      affect depolarization-evoked secretion prior to cation transport. FPL also
      accelerated the rate of secretion mediated by a Ca(2+)-impermeable channel made
      by replacing the wild type alpha(1)1.2 subunit was replaced with the mutant
      alpha(1)1.2/L775P. Furthermore, BayK and FPL modified the kinetic parameters of
      the fusion pore formation, which represent the initial contact between the
      vesicle lumen and the extracellular medium. A direct link between the channel
      activity and evoked secretion lends additional support to the view that the
      voltage-gated Ca(2+) channels act as a signaling molecular switch, triggering
      secretion upstream to ion transport into the cell.

PMID- 20054006
TI  - MRI criteria for MS in patients with clinically isolated syndromes.
AB  - In recent years, criteria for the diagnosis of multiple sclerosis (MS) have
      changed, mainly due to the incorporation of new MRI criteria. While the new
      criteria are a logical step forward, they are complex and-not surprisingly-a good
      working knowledge of them is not always evident among neurologists and
      neuroradiologists. In some circumstances, several MRI examinations are needed to
      achieve an accurate and prompt diagnosis. This provides an incentive for
      continued efforts to refine the incorporation of MRI-derived information into the
      diagnostic workup of patients presenting with a clinically isolated syndrome.
      Within the European multicenter collaborative research network that studies MRI
      in MS (MAGNIMS), a workshop was held in London in November 2007 to review
      information that may simplify the existing MS diagnostic criteria, while
      maintaining a high specificity that is essential to minimize false positive
      diagnoses. New data that are now published were reviewed and discussed and
      together with a new proposal are integrated in this position paper.

PMID- 20054008
TI  - Proliferation in the human ipsilateral subventricular zone after ischemic stroke.
AB  - BACKGROUND: It is uncertain whether neurogenesis occurs in humans after stroke.
      We studied the morphologic changes that occurred in the subventricular zone (SVZ)
      in patients who died following an acute ischemic stroke. METHODS: We examined
      coronal brain slices from patients who died after a first-ever cerebral
      nonlacunar infarction in the middle cerebral artery territory. We evaluated the
      morphologic changes in the ipsilateral and contralateral SVZ by light and
      electron microscopy. Using immunochemistry with Ki-67 and PCNA, we detected cell
      proliferation. We used Tuj-1 for immature neurons and PSA-NCAM for migrating
      cells. RESULTS: The study included 7 patients with a mean age of 82 +/- 5 (mean
      +/- SD) years; 4 were men. They died a mean of 10 +/- 5 days after the ischemic
      stroke. Brain samples were obtained a mean of 4 +/- 2 hours after death. In
      comparison with the contralateral SVZ, the following changes were observed in the
      ipsilateral SVZ: an increase in the width of the gap and ribbon layers, as well
      as in the cell density of the ribbon layer, an enlargement of the cytoplasmic
      volume of astrocytes, and an increase of Ki-67-positive cells. In the ipsilateral
      SVZ, mitoses and cells that stained for either Tuj-1 or PSA-NCAM markers were
      observed more frequently than in the contralateral SVZ. CONCLUSION: We found
      unequivocal evidence of active cell proliferation in the ipsilateral
      subventricular zone following an acute ischemic stroke in our patients.

PMID- 20054007
TI  - The 5-year direct medical cost of neonatal and childhood stroke in a population
      based cohort.
AB  - BACKGROUND: Despite increasing awareness of the long-term impact of pediatric
      stroke, there are few estimates of the costs of care. We examined acute and 5
      year direct costs of neonatal and childhood stroke in a population-based cohort
      in Northern California. METHODS: We obtained electronic cost data for 266
      children with neurologist-confirmed strokes, and 786 age-matched stroke-free
      controls, within the population of all children (<20 years) enrolled in a large
      managed care plan from 1996 through 2003. Cost data included all inpatient and
      outpatient health service costs including care at out-of-plan facilities. Costs
      were assessed for 5 years after stroke, expressed in 2003 US dollars, and
      stratified by age at stroke onset (neonatal, defined as <29 days of life, vs
      childhood). Stroke costs were adjusted for costs in stroke-free age-matched
      controls. RESULTS: Average adjusted 5-year costs for pediatric stroke are
      substantial: $51,719 for neonatal stroke and $135,161 for childhood stroke. The
      average cost of a childhood stroke admission was $81,869. The average birth
      admission cost for a neonatal stroke was $39,613; adjustment for control birth
      admission costs reduced this by only $4,792, suggesting the stroke accounted for
      88% of costs. Even among neonates whose strokes were not recognized until later
      in childhood ("presumed perinatal strokes"), admission costs exceeded those of
      controls. Chronic costs were highest in the first year poststroke, but continued
      to exceed control costs even in the fifth year by an average of $2,016.
      CONCLUSIONS: The economic burden of neonatal and childhood stroke is both large
      and sustained.

PMID- 20054009
TI  - A new sensitive MRI marker for memory deficits in normal aging.

PMID- 20054010
TI  - Hippocampal mean diffusivity and memory in healthy elderly individuals: a cross
      sectional study.
AB  - BACKGROUND: The relationship between age-related memory decline and hippocampal
      anatomic changes is a matter of debate. OBJECTIVES: To investigate the
      relationship between age-related memory decline and MRI hippocampal anatomic
      changes in a cohort of healthy individuals. METHODS: In this cross-sectional
      study, 76 healthy individuals (44 male and 32 female), ranging in age from 20 to
      80 years, were recruited from universities, community recreational centers,
      hospital personnel, and patients' relatives from 2005 to 2008. These individuals
      were submitted to a 3-T MRI protocol with a whole-brain T1-weighted and diffusion
      weighted scanning and a neuropsychological assessment. For each subject, we
      calculated the volumes of the total brain (gray + white matter) and hippocampi.
      The segmented hippocampi defined the binary masks where mean values of mean
      diffusivity (MD) and fractional anisotropy (FA) were calculated.
      Neuropsychological evaluation included tests of verbal memory (15 minutes delayed
      recall of a 15-word list) and visuospatial memory (20 minutes delayed
      reproduction of Rey complex figure). RESULTS: Hippocampal MD, but not hippocampal
      FA, hippocampal volume, or total brain volume, predicted performance of
      individuals beyond their 50s on tests of verbal and visuospatial memory.
      CONCLUSIONS: High mean diffusivity values in the hippocampal formation of healthy
      elderly individuals predict memory decline, as reflected by performance on tests
      of declarative verbal and visual-spatial memory.

PMID- 20054011
TI  - Clinical research in context: reexamining the distinction between research and
      practice.
AB  - At least since the seminal work of the (US) National Commission for the
      Protection of Human Subjects of Biomedical and Behavioral Research in the 1970s,
      a fundamental distinction between research and practice has underwritten both
      conceptual work in research ethics and regulations governing research involving
      human subjects. Notwithstanding its undoubted historical importance, I believe
      the distinction is problematic because it misrepresents clinical inquiry. In this
      essay, I aim to clarify the character of clinical inquiry by identifying crucial
      contextual constraints on justification constitutive of clinical science. This
      analysis shows that, from an epistemological point of view, clinical research and
      clinical practice are not sharply distinct but intimately intertwined. This
      result is important in its own right-an enriched understanding of the
      epistemology of clinical research is valuable in and of itself. But this result
      is also important because it has profound implications for the ethics of human
      subjects research.

PMID- 20054012
TI  - Disambiguating clinical intentions: the ethics of palliative sedation.
AB  - It is often claimed that the intentions of physicians are multiple, ambiguous,
      and uncertain-at least with respect to end-of-life care. This claim provides
      support for the conclusion that the principle of double effect is of little or no
      value as a guide to end-of-life pain management. This paper critically discusses
      this claim. It argues that proponents of the claim fail to distinguish two
      different senses of "intention," and that, as a result, they are led to
      exaggerate the extent to which clinical intentions in end-of-life contexts are
      ambiguous and uncertain. It argues further that physicians, like others who make
      life and death decisions, have a duty to get clear on what their intentions are.
      Finally, it argues that even if the principle of double effect should be
      rejected, clinical intentions remain ethically significant because they condition
      the meaning of extraordinary clinical interventions, such as that of palliative
      sedation.

PMID- 20054013
TI  - Emotional aging: recent findings and future trends.
AB  - Contrasting cognitive and physical decline, research in emotional aging suggests
      that most older adults enjoy high levels of affective well-being and emotional
      stability into their 70s and 80s. We investigate the contributions of age-related
      changes in emotional motivation and competence to positive affect trajectories.
      We give an overview on the recent literature on emotional processing and
      emotional regulation, combining evidence from correlational and experimental, as
      well as behavioral and neuroscience studies. In particular, we focus on emotion
      cognition interactions, including the positivity effect. Looking forward, we
      argue that efforts to link levels of emotional functioning with long-term
      outcomes, combining space- and time-sensitive measures of brain function, and
      developing interventions to improve life quality for older adults may further
      refine life-span theories and open promising avenues of empirical investigation.

PMID- 20054014
TI  - Timing, social support, and the effects of physical limitations on psychological
      distress in late life.
AB  - OBJECTIVES: Previous research shows that limitations in activities of daily
      living (ADLs) are related to greater psychological distress. This study uses a
      synthesis of life course and stress process perspectives to examine how social
      support resources and the timing of limitations intersect to shape the
      relationship between ADL limitations and changes in psychological distress.
      METHODS: Data are derived from a longitudinal study of adults aged 65 and older
      in the Washington, DC, metropolitan area over a 2-year period (2001-2003).
      RESULTS: ADL limitations are positively related to change in depressive symptoms.
      This relationship is weakened for older individuals, but only at higher levels of
      perceived social support. DISCUSSION: The contribution of this research is to
      offer a more nuanced view of the mental health consequences of physical
      limitations in late life by demonstrating that perceived social support provides
      an important context for age-variegated associations between ADL limitations and
      changes in psychological distress.

PMID- 20054015
TI  - Are older adults less or more physiologically reactive? A meta-analysis of age
      related differences in cardiovascular reactivity to laboratory tasks.
AB  - In this meta-analytic review of 31 laboratory studies, we examined if relatively
      older adults showed lower or higher cardiovascular reactivity compared with
      relatively younger adults. Results revealed that age was associated with lower
      heart rate reactivity but higher systolic blood pressure (SBP) reactivity during
      emotionally evocative tasks. Consistent with the predictions of dynamic
      integration theory, the result for SBP was moderated by the degree of task
      activation. These data are discussed in light of existing self-regulatory models
      and important future research directions.

PMID- 20054016
TI  - Re: International guidelines for management of metastatic breast cancer:
      combination vs sequential single-agent chemotherapy.

PMID- 20054017
TI  - StatBite: Radiation therapy plus cetuximab: skin reactions from 71 head and neck
      cancer patients from 11 institutions in Europe.

PMID- 20054018
TI  - New data cheer champions of the danger theory.

PMID- 20054019
TI  - Should cetuximab replace cisplatin in head and neck cancer?

PMID- 20054020
TI  - International study of hyperthermia spurs hope in U.S. advocates.

PMID- 20054021
TI  - Role of p21 and oxidative stress on renal tubular resistance after acute
      ischaemic injury.
AB  - BACKGROUND: Subsequent ischaemic episodes may induce renal resistance. P21 is a
      cell cycle inhibitor that may be induced by oxygen-free radicals and may have a
      protective effect in ischaemic acute kidney injury (AKI). This study aimed at
      evaluating the role of oxidative stress and p21 on tubular resistance in a model
      of acquired resistance after renal ischaemia and in isolated renal tubules.
      METHODS: Wistar rats were divided into: Group 1--sham; Group 2--sham operated and
      after 2 days submitted to 45-min ischaemia; and Group 3--45-min ischaemia
      followed after 2 days by a second 45-min ischaemia. Plasma urea was evaluated on
      Days 0, 2 and 4. Serum creatinine, creatinine clearance and oxidants
      (thiobarbituric acid-reactive substances) were determined 48 h after the second
      procedure (Day 4). Histology, immunohistochemistry for lymphocytes (CD3),
      macrophages (ED1), proliferation (PCNA) and apoptosis (TUNEL) were also
      evaluated. Rat proximal tubules (PTs) were isolated by collagenase digestion and
      Percoll gradient from control rats and rats previously subjected to 35 min of
      ischaemia. PTs were submitted to 15-min hypoxia followed by 45-min reoxygenation.
      Cell injury was assessed by lactate dehydrogenase release and hydroperoxide
      production (xylenol orange). RESULTS: Ischaemia induced AKI in Group 2 and 3
      rats. Subsequent ischaemia did not aggravate renal injury, demonstrating renal
      resistance (Group 3). Renal function recovery was similar in Group 2 and 3.
      Plasma and urine oxidants were similar among in Group 2 and 3. Histology
      disclosed acute tubular necrosis in Group 2 and 3. Lymphocyte infiltrates were
      similar among all groups whereas macrophages infiltrate was greater in Group 3.
      Cell proliferation was greater in Group 2 compared with Group 3. Apoptosis was
      similar in groups 2 and 3. The p21 expression was increased only in Group 3
      whereas it was similar in groups 1 and 2. PTs from the ischaemia group were
      sensitive to hypoxia but resistant to reoxygenation injury which was followed by
      lower hydroperoxide production compared to control PT. CONCLUSION: Renal
      resistance induced by ischaemia was associated with cell mechanism mediators
      involving oxidative stress and increased p21 expression.

PMID- 20054022
TI  - Transient azotaemia is associated with a high risk of death in hospitalized
      patients.
AB  - BACKGROUND: There are no suitably powered epidemiological studies of 'transient
      azotaemia' (TA). The objective of this study was to describe the epidemiology of
      TA and its independent association with hospital mortality. We hypothesized that
      TA would be associated with an independent increase in the risk of death.
      METHODS: We retrospectively studied all patients admitted to a university
      affiliated hospital in Australia between January 2000 and December 2002. Patients
      were excluded if they were <15 years old, were on chronic dialysis, had kidney
      transplant or if their length of hospital stay was <24 hours. We defined TA as
      rapidly recovering acute kidney injury (AKI) (return to no-AKI risk, injury,
      failure, loss, end stage (RIFLE) class within 72 hours of onset). We performed
      descriptive and comparative statistical analysis of data. The primary outcome of
      the study was the association between TA and hospital mortality in multivariate
      logistic regression analysis. RESULTS: Among 20 126 study patients, 3641 (18.1%)
      had AKI according to the RIFLE criteria and 1600 had AKI, which recovered during
      their hospital stay. Recovery of AKI occurred most commonly within 1 day after
      diagnosis (37.7%, n = 603). Furthermore, 1172 patients (73.3%) who recovered from
      AKI did so within 3 days (TA). After correcting for confounding factors, compared
      with patients without AKI, patients with TA had a significantly higher odds ratio
      for hospital mortality (2.26; 95% confidence interval: 1.85-2.76). CONCLUSIONS:
      Transient azotaemia is common in hospital patients, represents close to a third
      of all cases of AKI and is independently associated with a significantly higher
      risk of death.

PMID- 20054023
TI  - Quantifying the discontinuity of haemodialysis dose with time-averaged
      concentration (TAC) and time-averaged deviation (TAD).

PMID- 20054024
TI  - Hypertensive retinal changes, a screening tool to predict microalbuminuria in
      hypertensive patients: a cross-sectional study.
AB  - BACKGROUND: Studies have shown that hypertensive retinal changes (HRC) have a
      moderate accuracy in predicting microalbuminuria (MA) in elderly hypertensive
      patients (age >65 years). This study is an effort to identify a similar
      relationship in hypertensive patients aged <65 years. METHODS: Eight hundred and
      seventy consecutive hypertensive patients (males, 460; females, 410) aged 18-65
      years were assessed for their demographic characteristics and other laboratory
      variables. Patients with diabetes mellitus, metabolic syndrome and overt
      nephropathy were excluded. Optic fundi were assessed for HRC after pupillary
      dilatation, which were photographed. MA (albumin-creatinine ratio) was measured
      as an average of two non-consecutive overnight spot urine samples. RESULTS: Mean
      age was 45 +/- 13.4 years. Prevalence of MA and HRC was 36.7 and 38%,
      respectively. MA showed a strong association with HRC (P < 0.0001). Logistic
      regression identified the association between MA, duration of hypertension (HTN)
      (P = 0.016), smoking (P = 0.012) and elevated high-sensitivity C-reactive protein
      (HsCRP) (P = 0.032). HRC were associated with duration of HTN (P = 0.021) and
      smoking (P < 0.0001). Tests of accuracy for HRC as a predictor of MA showed
      sensitivity, specificity, positive predictive value, negative predictive value,
      likelihood ratio of a positive test and likelihood ratio of a negative test of
      78%, 86%, 76%, 87%, 5.2 and 0.26, respectively. Area under the receiver operating
      characteristic curve was 81%. Similarly, the individual grades of HRC had a
      moderate predictive accuracy. Higher grades had higher predictive accuracy. Inter
      and intra-observer correlation in interpreting HRC was acceptable. CONCLUSIONS:
      HRC of any grade have moderate accuracy in predicting MA and hence can be used as
      a cost-effective screening tool to predict MA especially in a resource-poor
      setting.

PMID- 20054025
TI  - A prospective observational study of catheter-related bacteraemia and thrombosis
      in a haemodialysis cohort: univariate and multivariate analyses of risk
      association.
AB  - BACKGROUND: Central venous catheterization is a fundamental component in
      delivering haemodialysis yet is associated with significantly higher complication
      rates than other methods of vascular access. In this study, we report results of
      univariate and multivariate analyses designed to identify and quantify
      independent risk association for catheterization type, clinical variables and
      laboratory variables with regard to the development of catheter-related
      bacteraemia (CRB) and catheter failure due to poor haemodialysis flow. METHODS: A
      2-year prospective study of all incident haemodialysis vascular access catheter
      insertions was conducted. Laboratory and clinical variables were recorded at
      catheter insertion, and the clinical course was followed up to the point of
      catheter removal. CRB and catheter failure due to poor flow were recorded as
      outcome events. Univariate and multivariate analyses were used to test for
      association between clinical and laboratory variables and outcome. RESULTS: Forty
      four thousand five hundred seventy-six catheter days were accumulated over the
      study period. Multivariate analysis demonstrated an independent association
      between non-tunnelled catheterization procedures and adverse outcomes compared
      with tunnelled central venous catheter insertions. Elevated modified Charlson
      comorbidity score was independently associated with the development of CRBc.
      Elevated C-reactive protein and low haemodialysis blood pump flow were
      independently associated with catheter failure due to poor flow. CONCLUSIONS: The
      data demonstrate that tunnelled central venous catheter insertions have an
      association with lower complication rates than non-tunnelled central venous
      catheter insertions that is independent of whether patients have acute or chronic
      renal failure, or high levels of comorbidity.

PMID- 20054026
TI  - Changes in renal risk factors versus renal function outcome during follow-up in a
      population-based cohort study.
AB  - BACKGROUND: Chronic kidney disease is a growing public health problem worldwide.
      Previous studies have identified several predictors for renal function decline.
      However, these studies used a single measurement of these risk factors.
      Therefore, the aim of this study was to investigate whether besides the baseline
      values of these risk factors, changes in risk factors are associated with
      subsequent rate of renal function loss. METHODS: Five thousand, six hundred and
      fifty-one participants in the Prevention of Renal and Vascular ENd-stage Disease
      (PREVEND) Study, a prospective, community-based cohort study, completed three
      screening visits during a follow-up of 6.5 years for detailed clinical and
      biochemical measurements. Change in renal function between the second and third
      screening rounds was chosen as the study parameter of interest. Changes in risk
      factors between the first and second screening rounds were incorporated as
      potential predictors for renal function loss in multivariable linear regression
      analyses. Based on the results of a previous study, gender-specific analyses were
      performed. RESULTS: In males, an increase in urinary albumin excretion (UAE),
      systolic blood pressure (SBP) and cholesterol was associated with a subsequent
      higher rate of renal function loss, whereas in females, increases in glucose
      levels were associated with an increase in renal function. For males, the
      analyses showed that both the baseline values and the change in UAE and
      cholesterol were significant predictors for increased rate of renal function loss
      during subsequent follow-up. With respect to SBP, when taking also the change in
      this variable into account, the baseline value was no longer a significant
      predictor for renal function loss. CONCLUSIONS: The results of the present study
      show the value of screening programs including repeated measurements of risk
      factors. Furthermore, these data indicate that, besides baseline values of risk
      factors, the changes over time in these factors should also be taken into account
      when developing 'Renal Risk Scores' to identify subjects in the general
      population who are at risk for accelerated renal function deterioration.

PMID- 20054027
TI  - The timing of dialysis initiation affects the incidence of renal replacement
      therapy.
AB  - BACKGROUND: Variations in the timing of dialysis initiation may explain some
      geographical variations in renal replacement therapy (RRT) incidence, but this
      effect has never been quantified. METHODS: Using data from the French Renal
      Epidemiology and Information Network registry, we quantified the association
      between RRT incidence in 2006-07 and median estimated glomerular filtration rate
      (eGFR) values before starting dialysis at the administrative district level with
      geographically appropriate methods. RESULTS: Crude RRT incidence varied from 80.4
      to 238.6 pmi between administrative districts, and median eGFR at dialysis
      initiation from 5.9 to 11.8 ml/min/1.73 m(2). Age- and sex-adjusted RRT
      incidence, associated with a 1.2-ml/min/1.73m(2) increase in median eGFR, rose 8%
      (4-13%) before and 9% (5-13%) after controlling for the effect of nine potential
      socioeconomic and medical risk factors. CONCLUSION: The impact of increased eGFR
      at initiation should be taken into account in guidelines recommending earlier
      dialysis start.

PMID- 20054028
TI  - Anaemia, microcytosis and sirolimus--is iron the missing link?
AB  - BACKGROUND: Sirolimus (SRL) has been implicated in the causation of post
      transplantation anaemia (PTA). It also induces profound red blood cell (RBC)
      microcytosis, which is poorly understood. METHODS: We conducted a retrospective
      study of SRL-induced anaemia and microcytosis [mean corpuscular volume (MCV) <80
      fl] with specific reference to iron homeostasis in 93 renal transplant patients
      treated with SRL for at least 3 months. RESULTS: While mean haemoglobin (Hb) and
      use of erythropoiesis-stimulating agents increased on SRL, RBC MCV underwent a
      significant decline throughout the whole study period of 24 months (P < 0.001)
      with the percentage of microcytosis rising from 2.2% at the start of SRL therapy
      to 40.7% after 24 months of therapy. An association between dMCV (MCV change on
      SRL) and SRL levels was shown at 3, 6, 12 and 24 months post-SRL (P = 0.015, P =
      0.037, P = 0.002 and P = 0.001, respectively). Intravenous (IV) iron
      administration was an independent predictor of dMCV at 12 and 24 months on SRL (P
      = 0.031 and P = 0.048, respectively). All patients who, after starting SRL and
      seeing a fall in MCV, then went on to receive IV iron therapy, showed a marked
      increase in MCV; this did not happen to patients given oral iron therapy.
      CONCLUSIONS: SRL is associated with mild anaemia, but marked RBC microcytosis
      these phenomena are correlated with SRL levels and the use of IV iron. Functional
      iron deficiency and impaired gastrointestinal absorption of iron seem likely
      explanations.

PMID- 20054029
TI  - Differential proteomic characterization between normal peritoneal fluid and
      diabetic peritoneal dialysate.
AB  - BACKGROUND: Since the mechanism of comorbidity and mortality in peritoneal
      dialysis is unclear, a comparison of peritoneal dialysate and normal peritoneal
      fluid may provide clues to the biological and pathological processes involved in
      peritoneal damage. METHODS: Peritoneal dialysate and control samples were
      collected from five diabetes mellitus (DM) patients and two patients receiving
      laparoscopic cholecystectomy. Proteins were separated by two-dimensional gel
      electrophoresis (2D-GE). After image analysis, altered gel spots between these
      two sample groups were subjected to tryptic digestion and mass spectrometry
      analysis. The results were searched against the NCBI database. RESULTS: A total
      of 26 protein spots were considered altered in 2D-GE between the two sample
      groups. After western blotting confirmation, vitamin D-binding protein,
      haptoglobin and alpha-2-microglobulin were at higher levels in the DM samples,
      while complement C4-A and IGK@ protein were at lower levels compared to the
      control samples. CONCLUSION: The loss of vitamin D-binding protein, haptoglobin
      and alpha-2-microglobulin may be due to a change in the permeability of the
      peritoneal membrane to middle-sized proteins or leakage from peritoneal
      inflammation. Lower levels of complement C4-A in dialysate may shed light on the
      beginning of peritoneal membrane scleroses.

PMID- 20054030
TI  - K+ starvation inhibits water-stress-induced stomatal closure via ethylene
      synthesis in sunflower plants.
AB  - The effect of water stress on stomatal closure in sunflower plants has been found
      to be dependent on K(+) nutrient status. When plants with different internal K(+)
      content were subjected to a water-stress period, stomatal conductance was reduced
      more markedly in plants with an adequate K(+) supply than in K(+)-starved plants.
      K(+) starvation promoted the production of ethylene by detached leaves, as well
      as by the shoot of whole plants. Water stress had no significant effect on this
      synthesis. The effect on stomatal conductance of adding 5 microM cobalt (an
      ethylene synthesis inhibitor) to the growing medium of plants subjected to water
      stress was also dependent on their K(+) nutritional status: conductance was not
      significantly affected in normal K(+) plants whereas it was reduced in K(+)
      starved plants. Cobalt had no harmful effects on growth, and did not alter the
      internal K(+) content in the plants. These results suggest that ethylene may play
      a role in the inhibiting effect of K(+) starvation on stomatal closure.

PMID- 20054031
TI  - Intracellular consequences of SOS1 deficiency during salt stress.
AB  - A mutation of AtSOS1 (Salt Overly Sensitive 1), a plasma membrane Na(+)/H(+)
      antiporter in Arabidopsis thaliana, leads to a salt-sensitive phenotype
      accompanied by the death of root cells under salt stress. Intracellular events
      and changes in gene expression were compared during a non-lethal salt stress
      between the wild type and a representative SOS1 mutant, atsos1-1, by confocal
      microscopy using ion-specific fluorophores and by quantitative RT-PCR. In
      addition to the higher accumulation of sodium ions, atsos1-1 showed inhibition of
      endocytosis, abnormalities in vacuolar shape and function, and changes in
      intracellular pH compared to the wild type in root tip cells under stress.
      Quantitative RT-PCR revealed a dramatically faster and higher induction of root
      specific Ca(2+) transporters, including several CAXs and CNGCs, and the drastic
      down-regulation of genes involved in pH-homeostasis and membrane potential
      maintenance. Differential regulation of genes for functions in intracellular
      protein trafficking in atsos1-1 was also observed. The results suggested roles of
      the SOS1 protein, in addition to its function as a Na(+)/H(+) antiporter, whose
      disruption affected membrane traffic and vacuolar functions possibly by
      controlling pH homeostasis in root cells.

PMID- 20054032
TI  - Functional analysis of GbAGL1, a D-lineage gene from cotton (Gossypium
      barbadense).
AB  - Cotton fibres originate from the outer ovule integument and D-lineage genes are
      essential for ovule development and their roles can be described by the 'ABCDE'
      model of flower development. To investigate the role of D-lineage genes during
      ovule and fibre development, GbAGL1 (GenBank accession number: FJ198049) was
      isolated from G. barbadense by using the SMART RACE strategy. Sequence and
      phylogenetic analyses revealed that GbAGL1 was a member of the D-lineage gene
      family. Southern blot analysis showed that GbAGL1 belonged to a low-copy gene
      family. Semi-quantitative RT-PCR and RNA in situ hybridization analyses revealed
      that the GbAGL1 gene in G. barbadense was highly expressed in whole floral bud
      primordia and the floral organs including ovules and fibres, but the signals were
      barely observed in vegetative tissues. GbAGL1 expression increased gradually with
      the ovule developmental stages. Over-expression of GbAGL1 in Arabidopsis caused
      obvious homeotic alternations in the floral organs, such as early flowering, and
      an extruded stigma, which were the typical phenotypes of the D-lineage gene
      family. In addition, a complementation test revealed that GbAGL1 could rescue the
      phenotypes of the stk mutant. Our study indicated that GbAGL1 was a D-lineage
      gene that was involved in ovule development and might play key roles in fibres
      development.

PMID- 20054033
TI  - Trace metal phytotoxicity in solution culture: a review.
AB  - Solution culture has been used extensively to determine the phytotoxic effects of
      trace metals. A review of the literature from 1975 to 2009 was carried out to
      evaluate the effects of As(V), Cd(II), Co(II), Cu(II), Hg(II), Mn(II), Ni(II),
      Pb(II), and Zn(II) on plants grown in solution. A total of 119 studies was
      selected using criteria that allowed a valid comparison of the results; reported
      toxic concentrations varied by five orders of magnitude. Across a range of plant
      species and experimental conditions, the phytotoxicity of the trace metals
      followed the trend (from most to least toxic): Pb approximately Hg >Cu >Cd
      approximately As >Co approximately Ni approximately Zn >Mn, with median toxic
      concentrations of (muM): 0.30 Pb, 0.47 Hg, 2.0 Cu, 5.0 Cd, 9.0 As, 17 Co, 19 Ni,
      25 Zn, and 46 Mn. For phytotoxicity studies in solution culture, we suggest (i)
      plants should be grown in a dilute solution which mimics the soil solution, or
      that, at a minimum, contains Ca and B, (ii) solution pH should be monitored and
      reported (as should the concentrations of the trace metal of interest), (iii)
      assessment should be made of the influence of pH on solution composition and ion
      speciation, and (iv) both the period of exposure to the trace metal and the plant
      variable measured should be appropriate. Observing these criteria will
      potentially lead to reliable data on the relationship between growth depression
      and the concentration of the toxic metal in solution.

PMID- 20054034
TI  - Patient-centered medical homes in Ontario.

PMID- 20054035
TI  - Health care reform and the need for comparative-effectiveness research.

PMID- 20054036
TI  - Nearing negotiations--reconciling key differences between House and Senate reform
      measures.

PMID- 20054037
TI  - Erythropoiesis-stimulating agents--time for a reevaluation.

PMID- 20054038
TI  - Ranking 37th--measuring the performance of the U.S. health care system.

PMID- 20054039
TI  - Comparative effectiveness and health care spending--implications for reform.

PMID- 20054040
TI  - Working with children to develop dimensions for a preference-based, generic,
      pediatric, health-related quality-of-life measure.
AB  - Use of preference-based measures (PBM) of health-related quality of life (HRQoL)
      is increasing. PBMs allow the calculation of quality-adjusted life years, which
      can be used in decision making. Research in the field of pediatric PBMs is
      lacking. This work is the first stage in the development of a new generic,
      pediatric PBM of HRQoL. Seventy-four qualitative interviews were undertaken with
      children to find out how health affects their lives. Sampling was purposive,
      balancing primarily for health within age, with gender and ethnicity as secondary
      criteria. Interviews covered a wide range of health conditions, and children were
      successfully able to articulate how their health affected their lives. Eleven
      dimensions of HRQoL were identified, covering social, emotional, and physical
      aspects, in common with other generic pediatric HRQoL measures, but differ by
      including feeling jeal'ous and feeling tired/weak and not including dimensions
      related to parental, family, or behavioral issues.

PMID- 20054041
TI  - Women's experiences of their violent behavior in an intimate partner
      relationship.
AB  - The purpose of this study was to describe women's perceptions of their violent
      behavior in a heterosexual partnership. The study followed the traditions of
      Husserlian descriptive phenomenology and the philosophy of existential
      phenomenology. Twenty-four volunteer Finnish women, aged 19 to 58 years, with a
      history of different manifestations of intimate partner violence (IPV)
      participated in open-ended interviews. The data were analyzed by the method
      developed by Colaizzi. The findings revealed that some of the women who opposed
      all violence on ethical grounds did not label their behavior as violent; some
      others minimized or justified their violent behavior. The findings offer
      professional insight into women's violent behavior and call for a readjustment in
      approaches to work in the area. Prevention and early identification of IPV
      require knowledge of the various manifestations and individual meanings of
      violence. Helping methods should provide women with the opportunity to talk about
      their abusive behavior and to confront and address their feelings of guilt,
      disappointment, and shame.

PMID- 20054042
TI  - Fathers: locating smoking and masculinity in the postpartum.
AB  - Many fathers mitigate the harm of their smoking by physically separating their
      smoking from their children and child care activities.The aim of this study was
      to empirically locate smoking and masculinities by detailing the highly gendered
      nature of the everyday places where fathers smoke. A masculinities framework was
      used to interpret interview and photovoice data drawn from an ethnographic study
      of fathers who smoke. Twenty participants completed individual interviews and
      contributed a total of 308 photographs to illustrate smoking through the eyes of
      fathers. The data were analyzed to describe the locations and contexts that
      facilitate and restrict participants' smoking. Three thematic findings-smoking on
      the job, the bifurcated domestic sphere, and solitary confinement-were drawn from
      the analyses to provide insights about when and where smoking does and does not
      occur, and offer direction for father-centered tobacco reduction interventions.

PMID- 20054043
TI  - Images in clinical medicine. Necrolytic migratory erythema.

PMID- 20054044
TI  - Googling ourselves--what physicians can learn from online rating sites.

PMID- 20054045
TI  - Preventing surgical-site infections in nasal carriers of Staphylococcus aureus.
AB  - BACKGROUND: Nasal carriers of Staphylococcus aureus are at increased risk for
      health care-associated infections with this organism. Decolonization of nasal and
      extranasal sites on hospital admission may reduce this risk. METHODS: In a
      randomized, double-blind, placebo-controlled, multicenter trial, we assessed
      whether rapid identification of S. aureus nasal carriers by means of a real-time
      polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal
      ointment and chlorhexidine soap, reduces the risk of hospital-associated S.
      aureus infection. RESULTS: From October 2005 through June 2007, a total of 6771
      patients were screened on admission. A total of 1270 nasal swabs from 1251
      patients were positive for S. aureus. We enrolled 917 of these patients in the
      intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure.
      All the S. aureus strains identified on PCR assay were susceptible to methicillin
      and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in
      the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in
      the placebo group (relative risk of infection, 0.42; 95% confidence interval
      [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most
      pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07
      to 0.62). There was no significant difference in all-cause in-hospital mortality
      between the two groups. The time to the onset of nosocomial infection was shorter
      in the placebo group than in the mupirocin-chlorhexidine group (P=0.005).
      CONCLUSIONS: The number of surgical-site S. aureus infections acquired in the
      hospital can be reduced by rapid screening and decolonizing of nasal carriers of
      S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)

PMID- 20054047
TI  - Clinical practice. Stage IV chronic kidney disease.

PMID- 20054046
TI  - Chlorhexidine-Alcohol versus Povidone-Iodine for Surgical-Site Antisepsis.
AB  - BACKGROUND: Since the patient's skin is a major source of pathogens that cause
      surgical-site infection, optimization of preoperative skin antisepsis may
      decrease postoperative infections. We hypothesized that preoperative skin
      cleansing with chlorhexidine-alcohol is more protective against infection than is
      povidone-iodine. METHODS: We randomly assigned adults undergoing clean
      contaminated surgery in six hospitals to preoperative skin preparation with
      either chlorhexidine-alcohol scrub or povidone-iodine scrub and paint. The
      primary outcome was any surgical-site infection within 30 days after surgery.
      Secondary outcomes included individual types of surgical-site infections.
      RESULTS: A total of 849 subjects (409 in the chlorhexidine-alcohol group and 440
      in the povidone-iodine group) qualified for the intention-to-treat analysis. The
      overall rate of surgical-site infection was significantly lower in the
      chlorhexidine-alcohol group than in the povidone-iodine group (9.5% vs. 16.1%;
      P=0.004; relative risk, 0.59; 95% confidence interval, 0.41 to 0.85).
      Chlorhexidine-alcohol was significantly more protective than povidone-iodine
      against both superficial incisional infections (4.2% vs. 8.6%, P=0.008) and deep
      incisional infections (1% vs. 3%, P=0.05) but not against organ-space infections
      (4.4% vs. 4.5%). Similar results were observed in the per-protocol analysis of
      the 813 patients who remained in the study during the 30-day follow-up period.
      Adverse events were similar in the two study groups. CONCLUSIONS: Preoperative
      cleansing of the patient's skin with chlorhexidine-alcohol is superior to
      cleansing with povidone-iodine for preventing surgical-site infection after clean
      contaminated surgery. (ClinicalTrials.gov number, NCT00290290.)

PMID- 20054048
TI  - Images in clinical medicine. Giant abdominal aortic aneurysm.

PMID- 20054049
TI  - Clinical problem-solving. Painful purple toes.

PMID- 20054050
TI  - Minimizing surgical-site infections.

PMID- 20054051
TI  - Variation in hospital mortality associated with surgery.

PMID- 20054052
TI  - Renal failure in cirrhosis.

PMID- 20054053
TI  - Parenteral nutrition in the critically ill patient.

PMID- 20054054
TI  - Screening for colorectal cancer.

PMID- 20054055
TI  - The case for integrated delivery systems.

PMID- 20054056
TI  - Hospital executives' perspectives on pay-for-performance and racial/ethnic
      disparities in care.
AB  - With increasing attention paid to reducing racial/ethnic disparities in care and
      the growth of pay-for-performance programs, policy makers and payers are
      considering the use of such incentive mechanisms to target disparities reduction.
      This article describes the results of qualitative interviews with hospital
      executives to assess the potential impact that such programs would have on
      hospitals and their minority patients. The authors find that executives have
      significant concerns regarding funding mechanisms and implementation costs,
      financial risks for safety net hospitals, and resource constraints, as well as
      how such programs can be used to create incentives to care for minority patients.
      The findings suggest that payers should be hesitant to use pay-for-performance as
      a mechanism for reducing disparities until a wide variety of concerns about the
      design of such programs can be addressed.

PMID- 20054057
TI  - Improving chronic illness care: findings from a national study of care management
      processes in large physician practices.
AB  - The use of evidence-based care management processes (CMPs) in physician practice
      is an important component of delivery-system reform.The authors used data from a
      2006-2007 national study of large physician organizations-medical groups and
      independent practice associations (IPAs) to determine the extent to which
      organizations use CMPs, and to identify external (market) influences and
      organizational capabilities associated with CMP use. The study found that
      physician organizations use about half of recommended CMPs, most commonly disease
      registries, specially trained patient educators, and performance feedback to
      physicians. Physician organizations that reported participating in quality
      improvement programs, having a patient-centered focus, and being owned by a
      hospital or health maintenance organization used more CMPs. IPAs and very large
      medical groups used more CMPs than smaller groups. Organizations externally
      evaluated on quality measures used more CMPs than other organizations. These
      findings can inform efforts to stimulate the adoption of best practices for
      chronic illness care.

PMID- 20054058
TI  - A.S.P.E.N. clinical guidelines: nutrition support of hospitalized pediatric
      patients with obesity.

PMID- 20054059
TI  - Nutrition in the intensive care unit: year in review 2008-2009.

PMID- 20054060
TI  - How you can improve the delivery of enteral nutrition in your PICU.

PMID- 20054062
TI  - A high-resolution association mapping panel for the dissection of complex traits
      in mice.
AB  - Systems genetics relies on common genetic variants to elucidate biologic networks
      contributing to complex disease-related phenotypes. Mice are ideal model
      organisms for such approaches, but linkage analysis has been only modestly
      successful due to low mapping resolution. Association analysis in mice has the
      potential of much better resolution, but it is confounded by population structure
      and inadequate power to map traits that explain less than 10% of the variance,
      typical of mouse quantitative trait loci (QTL). We report a novel strategy for
      association mapping that combines classic inbred strains for mapping resolution
      and recombinant inbred strains for mapping power. Using a mixed model algorithm
      to correct for population structure, we validate the approach by mapping over
      2500 cis-expression QTL with a resolution an order of magnitude narrower than
      traditional QTL analysis. We also report the fine mapping of metabolic traits
      such as plasma lipids. This resource, termed the Hybrid Mouse Diversity Panel,
      makes possible the integration of multiple data sets and should prove useful for
      systems-based approaches to complex traits and studies of gene-by-environment
      interactions.

PMID- 20054065
TI  - Active VSG expression sites of African trypanosomes are depleted of nucleosomes.

PMID- 20054063
TI  - Nucleosome landscape and control of transcription in the human malaria parasite.
AB  - In eukaryotic cells, chromatin reorganizes within promoters of active genes to
      allow the transcription machinery and various transcription factors to access
      DNA. In this model, promoter-specific transcription factors bind DNA to initiate
      the production of mRNA in a tightly regulated manner. In the case of the human
      malaria parasite, Plasmodium falciparum, specific transcription factors are
      apparently underrepresented with regards to the size of the genome, and
      mechanisms underlying transcriptional regulation are controversial. Here, we
      investigate the modulation of DNA accessibility by chromatin remodeling during
      the parasite infection cycle. We have generated genome-wide maps of nucleosome
      occupancy across the parasite erythrocytic cycle using two complementary assays-
      the formaldehyde-assisted isolation of regulatory elements to extract protein
      free DNA (FAIRE) and the MNase-mediated purification of mononucleosomes to
      extract histone-bound DNA (MAINE), both techniques being coupled to high
      throughput sequencing. We show that chromatin architecture undergoes drastic
      upheavals throughout the parasite's cycle, contrasting with targeted chromatin
      reorganization usually observed in eukaryotes. Chromatin loosens after the
      invasion of the red blood cell and then repacks prior to the next cycle. Changes
      in nucleosome occupancy within promoter regions follow this genome-wide pattern,
      with a few exceptions such as the var genes involved in virulence and genes
      expressed at early stages of the cycle. We postulate that chromatin structure and
      nucleosome turnover control massive transcription during the erythrocytic cycle.
      Our results demonstrate that the processes driving gene expression in Plasmodium
      challenge the classical eukaryotic model of transcriptional regulation occurring
      mostly at the transcription initiation level.

PMID- 20054066
TI  - The North American Veterinary Medical Education Consortium is launched.

PMID- 20054067
TI  - Diversity revisited.

PMID- 20054068
TI  - The life and times of Iverson C. Bell, Sr., DVM.

PMID- 20054069
TI  - Iverson Bell Award. Who can mentor minorities?

PMID- 20054070
TI  - The absence of African-American men in higher education and veterinary medicine.
AB  - Many studies have consistently indicated that the educational outcomes of Black
      men and boys are not on par with those of their White and female counterparts.
      Recent data suggest the same holds true for Black men in veterinary medicine.
      Drawing on national statistics and findings from an analysis of National
      Educational Longitudinal Study data, I present several recommendations for future
      policy and practice that can help combat the absence of Black men in the
      profession.

PMID- 20054071
TI  - DiVersity Matters: a review of the diversity initiative of the Association of
      American Veterinary Medical Colleges.
AB  - In 2004, the Association of American Veterinary Medical Colleges took the bold
      step of prioritizing diversity as a core value through the hiring of a full-time
      staff person. The organization then pressed forward in 2005 by launching a
      national plan devoted to increasing diversity in academic veterinary medicine. In
      the years since its inception, the DiVersity Matters initiative has overseen
      significant diversity changes in US colleges of veterinary medicine. Dedicated
      diversity programming can have a positive impact on academic veterinary medicine
      and the larger veterinary profession. This paper provides an overview of
      DiVersity Matters since its 2005 launch and how the initiative is evolving under
      the Association of American Veterinary Medical Colleges' Strategic Plan.

PMID- 20054072
TI  - Increasing minorities in veterinary medicine: national trends in science degrees,
      local programs, and strategies.
AB  - An "outsider" analysis of veterinary medicine in the context of national
      participation trends in science, technology, engineering, and mathematics
      suggests research to explain why students gravitate-or not-to the discipline and
      how the future of the profession may turn on the composition of the veterinary
      medicine faculty. Interventions to effect change in a range of classroom and
      institutional practices will determine the competitive advantage of the
      discipline relative to other health professions.

PMID- 20054073
TI  - The science of recruiting: implementing the vision of diversity.
AB  - There are multiple levels of involvement and influence in the process of
      recruiting minority students. The tiers of communication between an institution
      and a potential applicant can be visually depicted by the "recruitment funnel,"
      where a large pool of prospective students is narrowed, by specific outreach
      efforts, to represent those who actually inquire into your program, submit an
      application, and eventually enroll. Ultimately, those who are admitted must first
      apply. This article offers four specific strategies for success that pertain to
      the growing need for diversity in the future population of veterinary students.
      These four, ranging from composing your recruitment team to prioritizing line
      items for your budget, can serve to increase the quantity and quality of your
      next pool of high-quality minority applicants.

PMID- 20054074
TI  - Faculty ethics: ideal principles with practical applications.
AB  - Ethics in higher education is the subject of intense public attention, with
      considerable focus on faculty roles and responsibilities. Media reports and
      scholarly research have documented egregious misconduct that includes plagiarism,
      falsification of data, illicit teacher-student relationships, and grading bias.
      These accounts of wrongdoing often portray faculty ethicality as only a legal
      issue of obeying rules and regulations, especially in the teaching and research
      roles. My discussion challenges this narrow perspective and argues that
      characterizations of faculty ethicality should take into account broader
      expectations for professionalism such as collegiality, respect, and freedom of
      inquiry. First, I review the general principles of faculty ethics developed by
      the American Association of University Professors, as well as professional codes
      of ethics in specific professional fields. Second, I juxtapose the experiences of
      women and minority faculty members in relation to these general codes of ethics.
      This section examines three issues that particularly affect women and minority
      faculty experiences of ethicality: "chilly and alienating" academic climates,
      "cultural taxation" of minority identity, and the snare of conventional reward
      systems. Third, I suggest practical strategies to reconcile faculty practice with
      codes of ethics. My challenge is to the faculty as a community of practice to
      engage professional ethics as social and political events, not just legal and
      moral failures.

PMID- 20054075
TI  - Tying art and science to reality for recruiting minorities to veterinary
      medicine.
AB  - The challenge of this message, which is a synopsis of my presentation at the 2009
      Iverson Bell Symposium, is to look more holistically and at the how, what, when,
      and who of our recruitment activities in the context of the realities of managing
      resources, expectations, and metrics.

PMID- 20054076
TI  - Curriculum integration within the context of veterinary education.
AB  - Curriculum integration has been applied across a range of educational levels as a
      means of attempting to improve learning outcomes, but there is a paucity of
      information that has defined and explored curriculum integration as it relates to
      the teaching of veterinary science. A definition of curriculum integration in the
      teaching of veterinary science is suggested, which places students as lifelong
      learners at the center of the educational model. Learning activities are designed
      to help students see connections among disciplines and topics, thus reinforcing
      their relevance and helping them to apply their knowledge to different contexts.
      Curriculum integration at James Cook University in the first three years of the
      program has been promoted through the design of assessment, the use of case
      studies, imaging, and palpable anatomy, learning of clinical skills, a research
      project, animal handling, and a personal professional development program.
      Advantages and disadvantages of curriculum integration are discussed. Further
      work is needed to determine if this mode of curriculum design is able to produce
      veterinary graduates who are better able to meet the challenges of a changing
      workplace in the twenty-first century.

PMID- 20054077
TI  - A public-policy practicum to address current issues in human, animal, and
      ecosystem health.
AB  - There are recognized needs for cross-training health professionals in human,
      animal, and ecosystem health and for public health policy to be informed by
      experts from medical, science, and social science disciplines. Faculty members of
      the Community Health and Preventive Medicine Section at the University of
      Illinois at Urbana-Champaign, College of Veterinary Medicine, and the Institute
      of Government and Public Affairs, University of Illinois at Urbana-Champaign,
      have offered a public-policy course designed to meet those needs. The course was
      designed as a practicum to teach students the policy-making process through the
      development of policy proposals and to instruct students on how to effectively
      present accurate scientific, demographic, and statistical information to policy
      makers and to the public. All students substantially met the learning objectives
      of the course. This course represents another model that can be implemented to
      help students learn about complex, multifactorial issues that affect the health
      of humans, animals, and ecosystems, while promoting participation in public
      health policy development.

PMID- 20054078
TI  - Value and benefits of open-book examinations as assessment for deep learning in a
      post-graduate animal health course.
AB  - This study provides an overview of the perceptions of alumni in relation to their
      experience of open-book examinations (OBEs) as post-graduate students. This type
      of assessment was introduced as a way of allowing these adult learners to
      demonstrate their conceptual understanding and ability to apply knowledge in
      practice, which in theory would equip them with problem-solving skills required
      for the workplace. This study demonstrates that alumni-shown to be predominantly
      deep learners-typically regarded OBEs as less stressful than closed-book
      examinations, and as an effective way to assess the application of knowledge to
      real-life problems. Additional staff training and student induction, particularly
      for international students, are suggested as a means of improving the
      acceptability and effectiveness of OBEs.

PMID- 20054079
TI  - Undergraduate veterinary students' perceptions of the usefulness, focus, and
      application of epidemiology before and after epidemiology courses.
AB  - Student perception of the relevance of a topic is known to influence learning
      outcomes. To determine student perceptions of the usefulness, focus, and
      application of epidemiology, we conducted a study at two Australian veterinary
      schools in 2005. Veterinary students in year 3 at the University of Sydney and in
      year 5 at the University of Queensland completed a self-administered
      questionnaire at the commencement and conclusion of an epidemiology course. At
      both universities, while over 95% of students considered epidemiology to be
      "essential" or "quite useful" in cattle and sheep practice and in government
      practice, at the course end between 10% and 30% of students still did not
      consider epidemiology to be "essential" or "quite useful" in small-animal or
      equine practice. However, the percentage of students who considered that all
      veterinary work involved the application of epidemiological principles increased
      from 7% at course start to 15% at course end at the University of Sydney
      (p=0.188), and from 3% to 25% at the University of Queensland (p<0.001). The
      results indicate that, although some veterinary students, even at completion of
      an epidemiology course, still do not link epidemiology with an evidence-based
      medicine approach to patient care, undergraduate courses can positively change
      student perception of the usefulness, focus, and application of epidemiology.
      These findings will be used to refine the epidemiology courses analyzed to
      improve the learning outcomes of our students.

PMID- 20054080
TI  - Evaluation of radiographic interpretation competence of veterinary students in
      Finland.
AB  - In the evaluation of the clinical competence of veterinary students, many
      different definitions and methods are approved. Due to the increasing discussion
      of the quality of outcomes produced by newly graduated veterinarians, methods for
      the evaluation of clinical competencies should also be evaluated. In this study,
      this was done by comparing two qualitative evaluation schemes: the well-known
      structure of observed learning outcome (SOLO) taxonomy and a modification of this
      taxonomy. A case-based final radiologic examination was selected and the
      investigation was performed by classifying students' outcomes. These classes were
      finally put next to original (quantitative) scores and the statistical
      calculations were initiated. Significant correlations between taxonomies (0.53)
      and the modified taxonomy and original scores (0.66) were found and some
      qualitative similarities between evaluation methods were observed. In addition,
      some supplements were recommended for the structure of evaluation schemes,
      especially for the structure of the modified SOLO taxonomy.

PMID- 20054081
TI  - Faculty and students' self-assessment of client communication skills and
      professional ethics in three veterinary medical schools.
AB  - Client communication skills and professional ethics are areas that have received
      much attention in veterinary education in recent years. The objectives of this
      study were to: i) establish the confidence level of faculty teaching in three
      veterinary schools with regard to their client communication skills, ii)
      establish a baseline of professional ethics indicators in the same faculty, and
      iii) compare veterinary students of all levels to faculty in both areas. Students
      and faculty received identical questionnaires, including statements addressing
      client communication skills and professional ethics. The results indicate that
      students are generally comfortable with their communication skills, except in the
      areas of visual and/or audio aid use, handling emotional clients, and discussing
      costs of care and payment. Faculty were more comfortable than students in all
      areas of client communication, although they also had low confidence when dealing
      with costs of care and payment. Ethically, students and faculty answered
      similarly. Faculty showed a stronger belief that people are basically honest and
      ethical, but both cohorts responded similarly when asked about reporting an
      ethical violation admitted to them by their best friend. Further research is
      needed to determine whether students are communicating as effectively as they
      believe they are, with particular attention paid to improving communications with
      emotional clients and the business aspects of veterinary medicine. Additional
      work is needed to ensure that veterinary students are learning how to cope with
      ethical issues objectively. This may begin by ensuring that faculty are teaching
      and, more importantly, modeling these behaviors during the clinical year(s).

PMID- 20054082
TI  - Utilizing filmed authentic student-client interactions as a communication
      teaching tool.
AB  - In the past decade, communication training within veterinary medical training
      programs has received extensive publicity. Now, training programs are utilizing
      large-group lecturing, small-group discussions, and simulated client programs to
      address the need for veterinarians to effectively communicate with their clients.
      This paper presents a communication training protocol utilized at Kansas State
      University. The principle focus of this protocol is utilizing filmed student
      interactions with authentic veterinary medical clients. All veterinary medical
      students are required to film two interactions with hospital clientele. After
      each filmed session, students attend feedback sessions where communication
      strengths and weaknesses are discussed. Specific communication goals are
      identified for future interactions. A detailed description of the protocol
      follows, with preliminary impressions from students and instructors noted. As a
      promising tool for teaching communication skills, future directions for filmed
      authentic interactions are discussed.

PMID- 20054083
TI  - Use of the virtual ventilator, a screen-based computer simulation, to teach the
      principles of mechanical ventilation.
AB  - Examination scores from 109 students enrolled in the professional veterinary
      program at Washington State University were evaluated to determine the
      effectiveness and utility of the Virtual Ventilator computer simulation for
      teaching the principles of mechanical ventilation in an anesthesia course.
      Students were randomly assigned to either a live-animal mechanical ventilation
      laboratory (LIVE-1st) or a computer laboratory using the mechanical ventilation
      simulation (SIM-1st) in week 1. During week 2, students in the LIVE-1st group
      participated in the ventilation simulation while students in the SIM-1st group
      participated in the live-animal laboratory. Student knowledge was evaluated using
      two similar written quizzes administered following each laboratory. Student
      opinions concerning the value of the simulation were assessed using an online
      survey. Differences in quiz scores within and between groups were compared using
      t-tests while survey results were tabulated. A p value of less than 0.05 was
      considered significant. Within the LIVE-1st group, scores for the second quiz,
      which was taken after the students had completed the simulation exercise, were
      significantly higher than those obtained from the first quiz. Accordingly, the
      Virtual Ventilator simulation was at least equivalent to the live-animal
      laboratory in the ability to present information that was subsequently tested for
      on the quizzes. Students in the SIM-1st group reported that use of the simulation
      prior to a live-animal ventilation laboratory enhanced their understanding of and
      ability to provide mechanical ventilation to anesthetized patients. The Virtual
      Ventilator simulation appears to be a useful and well-received teaching tool.

PMID- 20054084
TI  - An animated model of reticulorumen motility.
AB  - Understanding reticulorumen motility is important to the assessment of ruminant
      health and optimal production, and in the recognition, diagnosis, and treatment
      of disease. Accordingly, the teaching of reticulorumen motility is a staple of
      all veterinary curricula. This teaching has historically been based on written
      descriptions, line drawings, or pressure tracings obtained during contraction
      sequences. We developed an animated model of reticulorumen motility and
      hypothesized that veterinary students would prefer use of the model over
      traditional instructional methods. First-year veterinary students were randomly
      allocated to one of two online learning exercises: with the animated model (Group
      A) or with text and line drawings (Group B) depicting reticulorumen motility.
      Learning was assessed with a multiple-choice quiz and feedback on the learning
      alternatives was obtained by survey. Seventy-four students participated in the
      study, including 38/42 in Group A and 36/36 in Group B. Sixty-four out of 72
      students (89%) responded that they would prefer use of the animated model if only
      one of the two learning methods was available. A majority of students agreed or
      strongly agreed that the animated model was easy to understand and improved their
      knowledge and appreciation of the importance of reticulorumen motility, and would
      recommend the model to other veterinary students. Interestingly, students in
      Group B achieved higher scores on examination than students in Group A. This
      could be speculatively attributed to the inclusion of an itemized list of
      contraction sequences in the text provided to Group B and failure of Group A
      students to read the text associated with the animations.

PMID- 20054085
TI  - Teaching transrectal palpation of the internal genital organs in cattle.
AB  - In this article, a simulation model for rectal palpation teaching in cows,
      Breed'n Betsy, is evaluated. Furthermore, the learning process of rectal
      palpation is depicted during a training period in live cows. In experiment 1,
      eight students were trained in live cows (group A) and nine students were trained
      using Breed'n Betsy (group B). After 25 palpations, their ability to localize and
      evaluate structures was evaluated in practical tests in live cows. Group A had
      higher results than group B (p<0.001) and were more skilled at localizing the
      uterus and localizing and evaluating the ovaries (p<0.05). Group B was better at
      pregnancy diagnosis (nonsignificant). Results suggest that Breed'n Betsy cannot
      fully replace training in live cows, but may be a valuable addition to the
      classical teaching method. Suggestions for future improvement are made. In
      experiment 2, 10 students were intensely trained in live cows throughout the year
      and evaluated in practical tests at three time points (September, January, and
      March). Results were analyzed as a function of time point and the category of
      experience (1: 0-50 cows; 2: 50-100 cows; 3: 100-150 cows; 4: 150-200 cows; 5:
      >200 cows). Results increased in time (p<0.05) and were higher in categories 3,
      4, and 5 than in category 1 (p<0.05). Although all of the students in the higher
      categories successfully localized the cervix, uterus, and ovaries, they had
      difficulties in interpreting these structures, suggesting that palpation of 200
      cows is insufficient to reach a consistent level of expertise.

PMID- 20054086
TI  - A rationale for SDS-PAGE of MHC isoforms as a gold standard for determining
      contractile phenotype.

PMID- 20054088
TI  - The profile of newborn screening coverage in China.
AB  - OBJECTIVE: To estimate provincial, regional and national newborn screening
      coverage throughout China. METHOD: Information about newborn screening was
      collected using a survey questionnaire from neonatal screening laboratories in
      China in 2006-2007. The total number of live births at the provincial and
      national levels was obtained from the Maternal and Child Health Information
      System (MCHIS) and the State Statistics Bureau (SSB), respectively, and was used
      to calculate the neonatal screening coverage at the provincial, regional and
      national levels. RESULTS: There were 185 laboratories providing neonatal
      screening services in China in 2007. The rates of national screening coverage in
      2006 and 2007 were 31.27% and 39.96%, respectively, based on live birth numbers
      reported by the SSB. Both of these estimates are lower than those calculated from
      live birth numbers reported by the MCHIS. The rates of coverage in the Eastern,
      Middle and Western regions were about 84.90%, 30.41% and 19.82%, respectively,
      based on the live birth numbers reported by the MCHIS. CONCLUSION: There are
      disparities in screening coverage between regions and between provinces
      throughout China, but the extent of this is difficult to ascertain because of the
      different systems of reporting live births. To calculate nationwide screening
      coverage it is probably appropriate to use the SSB data on live births. However,
      for provincial screening coverage the calculation is probably best based on the
      number of live births reported by the MCHIS once the validity of the MCHIS data
      is verified.

PMID- 20054089
TI  - An audit of the precipitating factors for haemolytic crisis among glucose-6
      phosphate dehydrogenase-deficient paediatric patients.
AB  - BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the
      most common genetic enzyme deficiencies leading to haemolytic anaemia. This study
      aimed to investigate the precipitating factors for haemolytic crisis in G6PD
      deficient paediatric patients in Jordan. METHOD: A retrospective study of data
      from the records of 258 paediatric patients admitted to a major paediatric
      hospital in North Jordan from January 2001 until April 2007. Patients included
      were G6PD-deficient children who were admitted to the hospital secondary to an
      episode of haemolytic anaemia. RESULTS: Of 258 paediatric patients, 244 (94.2%)
      had developed a haemolytic episode secondary to ingestion of fava beans. The
      remaining 14 children (5.8%) developed a haemolytic episode triggered by other
      factors, such as drugs and upper respiratory infections. CONCLUSION: Fava bean
      ingestion is the major precipitating factor for haemolytic anaemia episodes among
      G6PD-deficient children in Jordan.

PMID- 20054090
TI  - Influence of number of children on cancer screening among adults in the United
      States.
AB  - OBJECTIVE: To investigate the influence of children in the household on the
      likelihood of reporting cancer screening among adult men and women living in the
      United States. METHODS: 2004-2006 Medical Expenditure Panel Surveys (MEPS) were
      used to calculate the probability of self-reported cancer screening by number of
      children for adult men and women with adjustment for age, sex, marital status,
      race, education, current smoking status, obesity status, health insurance and
      having a usual health-care provider. RESULTS: The largest percentage of persons
      who had cancer screening was among respondents with no children in the household.
      In multivariate results, the probability of endoscopy was lower for persons with
      one child (24%) and two or more children (21%) in comparison with persons with no
      children living in the household (30%). Prostate-specific antigen (PSA) testing
      was lower among men with one child (17%) and two or more children (14%) in
      comparison with no children (22%). Pap smears were lower for women with two or
      more children (50%) but not different for women with one child (55%) in
      comparison with no children (56%). Mammograms were lower for women with one child
      (48%) and two or more children (42%) in comparison with no children in the
      household (55%). CONCLUSION: Across several different cancer screening
      modalities, the probability of screening is lower as the number of children in
      the household increases. Children may be an additional barrier to screening
      beyond factors such as socioeconomic status and access to care.

PMID- 20054091
TI  - Perceived barriers to flexible sigmoidoscopy screening for colorectal cancer
      among UK ethnic minority groups: a qualitative study.
AB  - OBJECTIVES: Evidence from existing UK screening programmes indicates disparities
      in uptake rates between UK ethnic minorities and the white majority population.
      The aim of this study was to explore barriers to the uptake of flexible
      sigmoidoscopy (FS) screening among UK ethnic minority populations. Specifically,
      beliefs about bowel cancer, perceived barriers to the test and ideas about ways
      to increase uptake were investigated. METHODS: Nine focus groups were conducted
      with a total of 53 participants from African-Caribbean, Gujarati Indian,
      Pakistani and white British communities. The topic guide was based on the Health
      Belief Model. Discussions were subject to framework analysis. RESULTS: Most
      participants expressed limited awareness of bowel cancer and cited this as a
      barrier to screening attendance. Anxiety regarding the invasiveness of the test,
      the bowel preparation and fear of a cancer diagnosis were common barriers across
      all ethnic groups. Language difficulties, failure to meet religious sensitivities
      and the expression of culturally influenced health beliefs were all discussed as
      specific barriers to uptake. Ethnically tailored health promotion and general
      practitioner involvement were recommended as ways of overcoming such barriers.
      CONCLUSIONS: The study was the first attempt to qualitatively explore barriers to
      FS bowel cancer screening in UK ethnic minorities. Most barriers were shared by
      all ethnic groups but health educators should supplement approaches designed for
      the majority to incorporate the specific needs of individual minority groups to
      ensure equitable access.

PMID- 20054092
TI  - Increasing participant recruitment into large-scale screening trials: experience
      from the CADET II study.
AB  - OBJECTIVES: Multicentre randomized trials frequently encounter difficulties in
      meeting their recruitment targets, resulting in extension of the trial and delays
      in implementation of the findings. We report on recruitment strategies
      implemented in a randomized evaluation of computer-aided detection in women
      attending routine screening in the UK Breast Screening Programme. SETTING: The
      target population for the trial was identified from an existing NHS database of
      women aged 50-70 invited for routine mammography in Coventry, Manchester and
      Nottingham, UK. Women were asked to consent to their mammograms being randomly
      allocated (in a ratio of 28:1:1) to one of three film-reading protocols. Trial
      information was mailed to women, along with the invitation to attend screening,
      and informed consent was obtained at the mammography appointment. Several
      strategies were implemented to increase recruitment rates. RESULTS: Recruitment
      rate increased significantly over time in the study (P < 0.0010 in all centres)
      with an overall acceptance rate of 46% of those attending screening. Mailing of
      the trial information sheet separate from the screening invitation in Coventry
      and Nottingham increased the recruitment rate, even after adjustment for the
      trend over time and for socioeconomic status of the attendees (P < 0.001).
      Extension of recruitment to mobile screening units in Nottingham, and the
      presence of an additional member of staff also improved recruitment (P < 0.001).
      Simplification of the trial information sheet had little effect. Increases in
      recruitment rate were not attributable to socioeconomic status of the attendees.
      CONCLUSIONS: In multicentre trials, monitoring of local recruitment protocols is
      required to ensure that each centre can maximize accrual targets.

PMID- 20054093
TI  - Screening histories of invasive breast cancers diagnosed 1989-2006 in the West
      Midlands, UK: variation with time and impact on 10-year survival.
AB  - OBJECTIVES: To examine variations in screening status category with time for
      20,862 invasive breast cancers diagnosed in the West Midlands between 1989 and
      2006, and to provide 10-year relative survival rates for each category. METHOD:
      Population-based breast screening was introduced in the West Midlands from 1988.
      Primary invasive breast cancers diagnosed from 1 April 1989 to 31 March 2006 in
      women eligible for breast screening were identified from the West Midlands Cancer
      Intelligence Unit's cancer registration database. A screening status was
      determined for each case using previously published methodology. RESULTS:
      Screening status rates are affected initially by the gradual rollout of the
      screening programme and more recently by the need to wait for three years before
      interval cancers and cancers in lapsed and non-attenders can be identified. In
      the steady-state period 1994-2003, 40.6% of invasive breast cancers were screen
      detected, 36.3% were interval cancers and 11.2% were cancers in non-attenders
      (NA). Ten-year relative survival was 89.6% for screen-detected breast cancers,
      73.3% for interval cancers and 51.9% for cancers in NA. CONCLUSION: The detection
      of invasive breast cancers by screening has improved over time, with an
      equivalent reduction in the numbers of interval cancers. This, together with a
      stable rate of cancers in NA and an improvement in the survival of women with
      interval cancers, suggests that further improvements in breast cancer mortality
      can be predicted. International comparisons of interval cancer rates are
      difficult due to interprogramme differences in the time between screens.

PMID- 20054094
TI  - Exploring the acceptability of two self-sampling devices for human papillomavirus
      testing in the cervical screening context: a qualitative study of Muslim women in
      London.
AB  - OBJECTIVES: We explored Muslim women's attitudes to self-sampling for human
      papillomavirus (HPV) in the context of cervical cancer screening and their
      responses to two self-sampling devices. SETTING: A Muslim community centre in
      north-east London. METHODS: Following a talk given on the subject of cervical
      cancer and HPV at the community centre, 28 women were recruited to take part in
      three focus group discussions. The discussion covered cervical screening, self
      sampling and HPV testing. Women were also asked for their responses to a swab
      self-sampling kit and a cervico-vaginal lavage device. Discussions were recorded
      and transcribed verbatim and the qualitative data were analysed using Framework
      Analysis. RESULTS: Participants were generally positive about cervical screening
      but acknowledged that some women in their community were reluctant to attend
      because of embarrassment, language difficulties, fear or because they were
      unmarried and did not want to communicate implicit messages about being sexually
      active. Self-sampling met a mixed response - women were concerned about not doing
      the test correctly, but thought that it might overcome barriers to screening for
      some women. HPV testing itself was thought to raise potentially difficult issues
      relating to trust and fidelity within marriages. Although most women said they
      would prefer to continue to have screening by a health professional, if they were
      to perform self-sampling, there was overwhelming preference for the swab over the
      lavage kit. CONCLUSIONS: There was limited enthusiasm for self-sampling in this
      group of Muslim women who had mostly attended for cervical screening, but a clear
      preference for a swab rather than a cervico-vaginal lavage.

PMID- 20054095
TI  - Barriers to cervical cancer screening attendance in England: a population-based
      survey.
AB  - OBJECTIVES: To explore barriers to cervical screening attendance in a population
      based sample, and to compare barriers endorsed by women who were up-to-date with
      screening versus those who were overdue. We also tested the hypothesis that women
      who were overdue for screening would be more generally disillusioned with public
      services, as indexed by reported voting behaviour in elections. SETTING: A
      population-based survey of women in England. METHODS: Face-to-face interviews
      were carried out with 580 women aged 26-64 years, and recruited using stratified
      random probability sampling as part of an omnibus survey. Questions assessed self
      reported cervical screening attendance, barriers to screening, voting behaviour
      and demographic characteristics. RESULTS: Eighty-five per cent of women were up
      to-date with screening and 15% were overdue, including 2.6% who had never had a
      smear test. The most commonly endorsed barriers were embarrassment (29%),
      intending to go but not getting round to it (21%), fear of pain (14%) and worry
      about what the test might find (12%). Only four barriers showed significant
      independent associations with screening status: difficulty making an appointment,
      not getting round to going, not being sexually active and not trusting the test.
      We found support for our hypothesis that women who do not attend for screening
      are less likely to vote in elections, even when controlling for barrier
      endorsement and demographic factors. CONCLUSIONS: Practical barriers were more
      predictive of screening uptake than emotional factors such as embarrassment. This
      has clear implications for service provision and future interventions to increase
      uptake. The association between voting behaviour and screening uptake lends
      support to the hypothesis that falling screening coverage may be indicative of a
      broader phenomenon of disillusionment, and further research in this area is
      warranted.

PMID- 20054096
TI  - The contributions of Louis I Woolf to the treatment, early diagnosis and
      understanding of phenylketonuria.
AB  - Early diagnosis of phenylketonuria (PKU) became a goal worth pursuing following
      demonstration of the efficacy of the dietary treatment conceived by Louis I
      Woolf. This paper narrates the history of this treatment, describes Woolf's role
      in the establishment of neonatal PKU screening and surveys his other
      contributions to our understanding of this condition. If Woolf, Centerwall, Baird
      and Berry had waited until all the scientific evidence about PKU that is now at
      our disposal had been brought to light, there would still be no neonatal
      screening programmes.

PMID- 20054097
TI  - The value of C-reactive protein in screening for future coronary heart disease
      events.
AB  - Measurement of C-reactive protein (CRP), an inflammatory marker associated with
      coronary heart disease (CHD) events, has been proposed as a means of screening
      for future CHD. In prospective studies about a three-fold increase in risk of CHD
      observed between the top fifth and bottom fifth of the CRP distribution has been
      taken to support the use of CRP as a screening test. This however gives an over
      optimistic impression of its value, because people in the middle of the
      distribution, where most CHD events occur, are excluded from the analysis. A
      different analysis is needed to assess whether screening is worthwhile.
      Examination of the relative frequency distributions of CRP in individuals from 22
      prospective studies of individuals without previous cardiovascular disease who
      subsequently did and did not have a CHD event shows that the detection rate (or
      sensitivity) was 18% for a false-positive rate of 10% (CRP cut-off 6.65 mg/L); a
      poor screening test. Whatever CRP cut-off is used, the overlap in CRP values
      between affected and unaffected individuals is too great for CRP to usefully
      discriminate between those who will and will not have a CHD event.

PMID- 20054098
TI  - FV-100: the most potent and selective anti-varicella zoster virus agent reported
      to date.
AB  - Bicyclic aryl furano pyrimidines represent the most potent anti-varicella zoster
      virus (VZV) agents reported to date. Lead compounds have 50% effective
      concentration (EC(50)) values in vitro that are in the subnanomolar range and
      selectivity index values that exceed 1 million. They have an absolute requirement
      for VZV thymidine kinase and most likely act as their phosphate forms. Some
      structural modification (such as aryl substitution in the base moiety) is
      tolerated, whereas little sugar modification is acceptable. The Cf1743 compound
      has proved to be significantly more potent than all reference anti-VZV compounds,
      as measured either by inhibition of infectious virus particles and/or viral DNA
      production; however, the high lipophilicity and very low water solubility of this
      compound gives poor oral bioavailability (<14%). Use of the modified cyclodextrin
      captisol and the synthesis of the 5'-monophosphate prodrug of Cf1743 has
      significantly improved water solubility, but does not give any enhancement in
      oral bioavailability. By contrast, the synthesis of the ether series does not
      give any further improvement in terms of solubility. The most promising prodrug
      to emerge to date is the hydrochloric salt of the 5'-valyl-ester, designated as
      FV-100. Its uptake into cells has been studied using fluorescent microscopy and
      biological assays, which have indicated that the compound is efficiently taken up
      by the cells after a short period of incubation.

PMID- 20054099
TI  - Factors affecting template usage in the development of K65R resistance in subtype
      C variants of HIV type-1.
AB  - BACKGROUND: We have shown that the K65R resistance mutation in HIV type-1 (HIV-1)
      reverse transcriptase (RT) is selected more rapidly in subtype C than subtype B
      HIV-1 in biochemical, cell culture and clinical studies. Template-usage
      experiments demonstrated that subtype C nucleotide coding sequences caused RT to
      preferentially pause, leading to K65R acquisition. This new study now further
      establishes the basis for differential occurrence of both K65R and thymidine
      analogue mutations (TAMs) between subtypes. METHODS: Gel-based nucleotide
      extension assays were used to study the homopolymeric sequence surrounding K65.
      RESULTS: When positive double-stranded DNA synthesis was evaluated from a
      negative single-stranded DNA template, pausing at the 67 region, which is linked
      to occurrence of TAMs, was alleviated with both subtype B and C templates at high
      dCTP concentrations, but this alleviation was more pronounced with the subtype C
      template. By contrast, pausing at the 65 region on the subtype C but not subtype
      B template always occurred and was not alleviated at high levels of nucleotide
      triphosphates or by other means. Furthermore, templates containing repeats of the
      homopolymeric sequence spanning codons 64-66 of pol showed corresponding pausing
      repeats at the 65 region with the subtype C template only. Inverted RNA and DNA
      templates both displayed pausing at position K65 for the subtype C template and a
      ladder of pausing events culminating at codon 67 for the subtype B templates.
      CONCLUSIONS: These results further establish a mechanistic basis for the
      exclusion of both K65R and TAMs on single templates as well as the preferential
      acquisition of K65R in subtype C viruses.

PMID- 20054100
TI  - The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent
      antiviral properties.
AB  - BACKGROUND: Olomoucine II, the most recent derivative of roscovitine, is an
      exceptionally potent pharmacological inhibitor of cyclin-dependent kinase
      activities. Here, we report that olomoucine II is also an effective antiviral
      agent. METHODS: Antiviral activities of olomoucine II were tested on a range of
      human viruses in in vitro assays that evaluated viral growth and replication.
      RESULTS: Olomoucine II inhibited replication of a broad range of wild-type human
      viruses, including herpes simplex virus, human adenovirus type-4 and human
      cytomegalovirus. Olomoucine II also inhibited replication of vaccinia virus and
      herpes simplex virus mutants resistant to conventional acyclovir treatment. This
      report is the first demonstration of a poxvirus being sensitive to a cyclin
      dependent kinase inhibitor. The antiviral effects of olomoucine II could be
      observed at lower concentrations than with roscovitine, although both were short
      term. A remarkable observation was that olomoucine II, when used in combination
      with the DNA polymerase inhibitor cidofovir, was able to almost completely
      eliminate the spread of infectious adenovirus type-4 progeny from infected cells.
      CONCLUSIONS: Our results show that when targeting two complementary antiviral
      mechanisms, strongly additive effects could be observed.

PMID- 20054101
TI  - Activity of isatine-sulfadimidine derivatives against 2009 pandemic H1N1
      influenza virus in cell culture.
AB  - BACKGROUND: The development of antiviral drugs has provided crucial new means to
      mitigate or relieve the debilitating effects of many viral pathogens. New classes
      of inhibitors are essential to combat swine influenza viral infection. METHODS: A
      series of isatine-sulfadimidine derivatives were screened for antiviral activity
      against swine influenza A/California/07/2009 (H1N1) virus in Madin-Darby canine
      kidney (MDCK) cell culture. Cytotoxicity of the synthesized compounds was also
      tested in uninfected MDCK cells. RESULTS: All the compounds inhibit the influenza
      A (H1N1) in MDCK cells. The most active compounds, SPIII-5Br and SPIII-5H,
      inhibited virus-induced cytopathology by 50% at 27 and 30 microM, respectively,
      with 50% cytotoxicity occurring at a much higher dose (975-1,000 microM). The
      positive control compound ribavirin inhibits the replication of the virus at 18
      microM and cytotoxic concentration was found to be >1,000 microM. CONCLUSIONS:
      SPIII-5Br and SPIII-5H exhibited potency in the same range as ribavirin and are
      suitable candidate molecules for further investigation.

PMID- 20054102
TI  - Bifurcating microchannels as a scaffold to induce separation of regenerating
      neurites.
AB  - Many neural interfacing strategies, such as the sieve electrode and the cultured
      probe, rely on neurite growth to establish neural contact. But this growth is
      subject to natural fasciculation, compromising the effectiveness of these
      interfacing strategies by reducing potential selectivity. This in vitro study
      shows that the fasciculation mechanism can be manipulated by providing an
      appropriate microchannel scaffold to guide and influence growth, thereby
      achieving a high degree of selectivity. The microchannels employed have a
      bifurcation from a primary channel into two secondary channels. This bifurcating
      microstructure was able to support and promote fasciculated growth over 70% of
      the time for microchannels widths of 2.5, 5, 10 and 20 microm. Fasciculation is
      shown to be a strong force during ingrowth, with the initiation of neurite
      separation related to random spatial exploration. Narrower microchannels initiate
      separated growth better. Once separated growth starts fasciculation results in an
      even distribution of neurite growth across the bifurcation. The reduction from 20
      microm to 10 microm wide channels also resulted in a 3-fold decrease in ingrowing
      neurites performing 180 degrees turns to exit the microchannel via the entrance.
      No neurite turning was observed for both the 5 and 2.5 microm wide channels.

PMID- 20054103
TI  - In vivo electrochemical characterization and inflammatory response of multiwalled
      carbon nanotube-based electrodes in rat hippocampus.
AB  - Stimulating neural electrodes are required to deliver charge to an environment
      that presents itself as hostile. The electrodes need to maintain their electrical
      characteristics (charge and impedance) in vivo for a proper functioning of neural
      prostheses. Here we design implantable multi-walled carbon nanotubes coating for
      stainless steel substrate electrodes, targeted at wide frequency stimulation of
      deep brain structures. In well-controlled, low-frequency stimulation acute
      experiments, we show that multi-walled carbon nanotube electrodes maintain their
      charge storage capacity (CSC) and impedance in vivo. The difference in average
      CSCs (n = 4) between the in vivo (1.111 mC cm(-2)) and in vitro (1.008 mC cm(-2))
      model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed).
      We also report on the transcription levels of the pro-inflammatory cytokine IL
      1beta and TLR2 receptor as an immediate response to low-frequency stimulation
      using RT-PCR. We show here that the IL-1beta is part of the inflammatory response
      to low-frequency stimulation, but TLR2 is not significantly increased in
      stimulated tissue when compared to controls. The early stages of
      neuroinflammation due to mechanical and electrical trauma induced by implants can
      be better understood by detection of pro-inflammatory molecules rather than by
      histological studies. Tracking of such quantitative response profits from better
      analysis methods over several temporal and spatial scales. Our results concerning
      the evaluation of such inflammatory molecules revealed that transcripts for the
      cytokine IL-1beta are upregulated in response to low-frequency stimulation,
      whereas no modulation was observed for TLR2. This result indicates that the early
      response of the brain to mechanical trauma and low-frequency stimulation
      activates the IL-1beta signaling cascade but not that of TLR2.

PMID- 20054104
TI  - Immunogenicity of a new HIV-1 DNA construct in a BALB/c mouse model.
AB  - BACKGROUND: Cell mediated immunity, especially cytotoxic T cell responses against
      HIV-1 infection, plays a critical role in controlling viral replication and
      disease progression. DNA vaccine is a novel technology which is known to
      stimulate strong cellular immune responses. Many DNA vaccines have been tested
      for HIV infection but there is still no effective vaccine against this infection.
      Construction of a vaccine consisting of multiple conserved and immunogenic
      epitopes may increase vaccine efficacy. OBJECTIVE: In the present study a DNA
      vaccine candidate constructed from HIV-1 P24-Nef was evaluated and cellular
      immune responses were assessed in murine BALB/c model. METHODS: HIV-1 P24-Nef
      gene was cloned in PCDNA3.1 expression vector. Mice were immunized with DNA
      construct and IL-4 and IFN-gamma evaluation was performed using ELISPOT.
      Cytotoxicity response was evaluated with Granzyme B ELISPOT assay and lymphocyte
      proliferation was evaluated with LTT assay. RESULTS: Analysis of immune responses
      showed that, compared to control groups, the candidate vaccine induced production
      of higher levels of both IL-4 and IFN-gamma (p<0.05). Cytotoxicity and lymphocyte
      proliferation responses of mice vaccinated with the candidate vaccine were
      significantly increased compared to control groups (p<0.05). CONCLUSION: HIV-1
      P24-Nef DNA construct displayed strong immunogenicity in a murine model.

PMID- 20054105
TI  - Heterologous immunization, a way out of the problem of monoclonal antibody
      production against carcinoma antigen 125.
AB  - BACKGROUND: Monoclonal antibodies (mAbs) are essential tools for many molecular
      immunology investigations, epitope mapping and molecular modelling, clinical
      laboratory diagnostic tests and immunotherapy. Humoral immune response of
      immunized animals largely depends on the nature of antigen and the immunization
      technique. Polysaccharides and heavily-glycosylated proteins are very elusive
      targets incapable of mounting long-lasting, high affinity antibody responses.
      Carcinoma antigen 125 (CA 125), a well known tumor marker of ovarian cancer, is a
      mucin type antigen consisting of repetitive units of heavily glycosylated
      moieties which render production of mAbs very difficult. OBJECTIVE: To evaluate
      the efficacy of heterologous antigen preparations as a way of mouse immunization
      in the production of anti-CA 125 mAb. METHODS: Two different protocols of
      immunization were used for priming of NMRI mice. In the first method, mice
      conventionally immunized by three intraperitoneal injections of purified CA 125
      and boosted by the antigen three days before fusion. In the second approach, mice
      were primed by three intraperitoneal injections of living CA 125 positive cells
      of OVCAR-3 cell line, and boosted by intravenous injection of the purified
      extracellular domain of CA 125. Production of mAb was performed by standard
      hybridoma technology and mAbs were characterized by different immunoassays.
      RESULTS: The first method failed to produce stable clones despite six time
      fusion. A total of ten stable clones, however, were produced in the second
      approach. Some of the clones were characterized and found to have excellent
      immunoreactivity when tested by ELISA assay, western blotting, intracellular and
      surface immunofluorescent staining of OVCAR-3 cell line and immunohistochemical
      staining of ovarian cancer tissues. CONCLUSION: Altogether the results of the
      present study clearly showed that heterologous antigen preparation is the method
      of choice for immunization when production of monoclonal antibody against highly
      glycosylated poorly immunogenic antigens is concerned.

PMID- 20054106
TI  - Mesenchymal stem cells do not suppress lymphoblastic leukemic cell line
      proliferation.
AB  - BACKGROUND: Several studies have demonstrated the immunosuppresive effects of
      mesenchymal stem cells (MSCs) in allogeneic or mitogenic interactions. Cell-cell
      contact inhibition and secretion of suppressive soluble factors have been
      suggested in this regard. OBJECTIVE: To investigate if adipose derived MSCs could
      inhibit Jurkat lymphoblastic leukemia T cell proliferation during coculture.
      METHODS: Adherent cells with the ability of cellular growth were isolated from
      normal adipose tissues. Initial characterization of growing cells by flow
      cytometry suggested their mesenchymal stem cell characteristics. Cells were
      maintained in culture and used during third to fifth culture passages. Jurkat or
      allogeneic peripheral blood mononuclear cells (PBMCs) were labeled with carboxy
      fluorescein diacetate succinimidyl ester and cocultured with increasing doses of
      MSCs or MSC culture supernatant. Proliferation of PBMCs or Jurkat cells under
      these conditions was assessed by flow cytometry after 2 and 3 days of coculture,
      respectively. RESULTS: Results showed the expression of CD105, CD166 and CD44,
      and the absence of CD45, CD34 and CD14 on the surface of MSC like cells.
      Moreover, initial differentiation studies showed the potential of cell
      differentiation into hepatocytes. Comparison of Jurkat cell proliferation in the
      presence and absence of MSCs showed no significant difference, with 70% of cells
      displaying signs of at least one cell division. Similarly, the highest
      concentration of MSC culture supernatant (50% vol/vol) had no significant effect
      on Jurkat cell proliferation (p>0.6). The same MSC lots significantly suppressed
      the allogeneic PHA activated PBMCs under similar culture conditions. CONCLUSION:
      Using Jurkat cells as a model of leukemia T cells, our results indicated an
      uncertainty about the suppressive effect of MSCs and their inhibitory metabolites
      on tumor or leukemia cell proliferation. Additional systematic studies with MSCs
      of different sources are needed to fully characterize the immunological
      properties of MSCs before planning clinical applications.

PMID- 20054107
TI  - In vitro fertilized embryos do not secrete detectable HLA-G on day two.
AB  - BACKGROUND: Pregnancy is a successful transplantation. The factors evading
      rejection of the fetus are poorly understood. Recently an interest has grown, in
      HLA-G molecules as one of these factors. Since these antigens are mainly
      expressed on the surface of cytotrophoblasts that are in direct contact with
      maternal tissues, it has been suggested that these molecules may have a role in
      induction of immune tolerance in mothers. OBJECTIVE: to find the association of
      soluble HLA-G (sHLA-G) and the success of pregnancy with intracytoplasmic sperm
      injection (ICSI) procedure. METHODS: In this study, the supernatant of 287
      individually cultured embryos corresponding to 96 women under ICSI procedure were
      assayed for soluble HLA-G1 and G5 by a sandwich ELISA. RESULTS: Clinical
      pregnancy successfully occurred in 30 of candidates. No differences in clinical
      parameters (age, infertility duration, stimulation regimen) were observed between
      pregnant and nonpregnant women under ICSI procedure. None of the embryo
      supernatants in either group showed any detectable sHLA-G molecules. CONCLUSION:
      Our results showed that detectable level of sHLA-G is not produced by day 2
      embryos and such a measurement may not provide reliable information for embryo
      selection and estimation of pregnancy success.

PMID- 20054108
TI  - Performance of latex agglutination test (KAtex) in diagnosis of visceral
      leishmaniasis in Iran.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is an endemic disease in some parts of
      Iran. Many techniques have been used for diagnosis of VL, among which the urine
      based latex agglutination test (KAtex) is a promising one. OBJECTIVE: To compare
      three diagnostic tests of VL including KAtex, ELISA and Direct Agglutination Test
      (DAT) in VL patients and healthy controls in the south west of Iran. METHODS:
      Serum (n = 29) and urine samples (n = 31) were collected from parasitologically
      confirmed VL patients. Control samples were obtained from healthy individuals (n
      = 61) and also from patients with infectious diseases other than VL. The
      collected serum samples were tested by DAT and ELISA using crude antigen from
      promastigotes of Leishmania infantum and the urine samples were tested by KAtex.
      RESULTS: Sensitivity and specificity of KAtex for diagnosis of VL was found to be
      83.9% and 100%, respectively. Sensitivities of DAT and ELISA were 93.1% and 86.2%
      and their specificities were 100% and 90.5%, respectively. CONCLUSION: KAtex
      yielded a satisfactory sensitivity and specificity in diagnosis of VL in Iran and
      can be recommended as a rapid, field applicable and reliable test for diagnosis
      of VL in this region.

PMID- 20054109
TI  - Qualitative and semi-quantitative comparison of an rK39 strip test and direct
      agglutination test for detection of anti-Leishmania donovani antibodies in the
      Sudan.
AB  - BACKGROUND: Until now, the comparison of the rK39 strip test (RKT) and direct
      agglutination test (DAT) for detection of visceral leishmaniasis (VL) is
      exclusively based on either positive or negative qualification of the reaction
      outcome. OBJECTIVE: In this study, we compared the diagnostic performance of RKT
      and DAT for VL both qualitatively and semi-quantitatively. METHODS: For
      comparison based on semi-quantitative grounds, the execution of RKT and DAT was
      according to the standard procedures. For comparison on semi-qualitative grounds
      with DAT, the RKT was applied to aliquots from positive samples that were two
      fold serially diluted in saline to determine, as for the DAT, the end-point
      reaction in RKT. RESULTS: While qualitatively both RKT and DAT demonstrated
      comparable reliability for VL detection (sensitivity = 96% and specificity =
      98.7% or 99.3%), no significant correlation (r = 0.13) could be established
      between intensities of their positive reactions in 25 cases studied. A negative
      correlation was further determined in those 25 VL cases between the positive
      intensities of the RKT and antibody levels measured semi-quantitatively with the
      same procedure (r = -0.36) or the DAT (r = -0.30). Irrespective of the low,
      moderate or high antibody levels measured with RKT (< or = 1:8 and 1:16-1:32 > or
      = 1:256) or DAT (< or = 1:25,600 and 1:51,200- 1:409,600 > or = 1:3,276,800) in
      patients with confirmed or unconfirmed VL infection, exclusively strong positive
      intensities were obtained with RKT. CONCLUSION: For further optimizing diagnosis
      and simultaneously assessing magnitude of immune response to L. donovani
      infection in Sudanese patients, the combined application of RKT and DAT is
      recommended.

PMID- 20054110
TI  - Tehranolide could shift the immune response towards Th1 and modulate the intra
      tumor infiltrated T regulatory cells.
AB  - BACKGROUND: Artemisia diffusa contains a new type of sesquiterpene lactone with
      an endoperoxide group (Tehranolide). OBJECTIVE: Due to the existing similarity
      between the structures of Tehranolide and Artemisinin, it was hypothesized that
      Tehranolide would have similar effects as Artemisinin. In this study, the
      immunotherapeutic effectiveness of Tehranolide was investigated by direct intra
      tumoral injection. METHODS: Tehranolide was purified from Artemisia diffusa, and
      its effect on the tumor volume was investigated. The splenocyte proliferation,
      shifting of cytokine profile, and the presence of naturally-occurring
      CD4+CD25+Foxp3+ Treg cells were assessed to describe the anti-tumor immune
      response. RESULTS: Analysis of immune response showed that, intra-tumoral
      injection of Tehranolide decreased the rate of tumor growth compared to control
      group. Furthermore, the proliferative response of mice treated with Tehranolide
      was enhanced. In comparison with the control group, production of both IL-4 and
      IFN-gamma was induced (p<0.05). The results indicated a decrease in tumor
      CD4+CD25+Foxp3+ T lymphocytes in the Tehranolide-treated group compared to the
      control group. CONCLUSION: Treatment of tumors with Tehranolide attenuated
      CD4+CD25+Foxp3+ Treg cell-mediated immune suppression and elicited a persistent
      anti-tumor immunity against cancer.

PMID- 20054111
TI  - Structure of hypothetical Mo-cofactor biosynthesis protein B (ST2315) from
      Sulfolobus tokodaii.
AB  - The structure of a probable Mo-cofactor biosynthesis protein B from Sulfolobus
      tokodaii, belonging to space group P6(4)22 with unit-cell parameters a = b =
      136.68, c = 210.52 A, was solved by molecular replacement to a resolution of 1.9
      A and refined to an R factor and R(free) of 16.8% and 18.5%, respectively. The
      asymmetric unit contains a trimer, while the biologically significant oligomer is
      predicted to be a hexamer by size-exclusion chromatography. The subunit structure
      and fold of ST2315 are similar to those of other enzymes that are known to be
      involved in the molybdopterin- and molybdenum cofactor-biosynthesis pathways.

PMID- 20054112
TI  - Structure of SurE protein from Aquifex aeolicus VF5 at 1.5 A resolution.
AB  - SurE is a stationary-phase survival protein found in bacteria, eukaryotes and
      archaea that exhibits a divalent-metal-ion-dependent phosphatase activity and
      acts as a nucleotidase and polyphosphate phosphohydrolase. The structure of the
      SurE protein from the hyperthermophile Aquifex aeolicus has been solved at 1.5 A
      resolution using molecular replacement with one dimer in the asymmetric unit and
      refined to an R factor of 15.6%. The crystal packing reveals that two dimers
      assemble to form a tetramer, although gel-filtration chromatography showed the
      presence of only a dimer in solution. The phosphatase active-site pocket was
      occupied by sulfate ions from the crystallization medium.

PMID- 20054113
TI  - Structure of D-lactate dehydrogenase from Aquifex aeolicus complexed with NAD(+)
      and lactic acid (or pyruvate).
AB  - The crystal structure of D-lactate dehydrogenase from Aquifex aeolicus (aq_727)
      was determined to 2.12 A resolution in space group P2(1)2(1)2(1), with unit-cell
      parameters a = 90.94, b = 94.43, c = 188.85 A. The structure was solved by
      molecular replacement using the coenzyme-binding domain of Lactobacillus
      helveticus D-lactate dehydrogenase and contained two homodimers in the asymmetric
      unit. Each subunit of the homodimer was found to be in a ;closed' conformation
      with the NADH cofactor bound to the coenzyme-binding domain and with a lactate
      (or pyruvate) molecule bound at the interdomain active-site cleft.

PMID- 20054114
TI  - The structure of an archaeal ribose-5-phosphate isomerase from Methanocaldococcus
      jannaschii (MJ1603).
AB  - Ribose-5-phosphate isomerase is a ubiquitous intracellular enzyme of bacterial,
      plant and animal origin that is involved in the pentose phosphate cycle, an
      essential component of cellular carbohydrate metabolism. Specifically, the enzyme
      catalyses the reversible conversion of ribose 5-phosphate to ribulose 5
      phosphate. The structure of ribose-5-phosphate isomerase from Methanocaldococcus
      jannaschii has been solved in space group P2(1) to 1.78 A resolution using
      molecular replacement with one homotetramer in the asymmetric unit and refined to
      an R factor of 14.8%. The active site in each subunit was occupied by two
      molecules of propylene glycol in different orientations, one of which corresponds
      to the location of the phosphate moiety and the other to the location of the
      furanose ring of the inhibitor.

PMID- 20054115
TI  - Structure of a putative beta-phosphoglucomutase (TM1254) from Thermotoga
      maritima.
AB  - The structure of TM1254, a putative beta-phosphoglucomutase from T. maritima, was
      determined to 1.74 A resolution in a high-throughput structural genomics
      programme. Diffraction data were obtained from crystals belonging to space group
      P22(1)2(1), with unit-cell parameters a = 48.16, b = 66.70, c = 83.80 A, and were
      refined to an R factor of 19.2%. The asymmetric unit contained one protein
      molecule which is comprised of two domains. Structural homologues were found from
      protein databases that confirmed a strong resemblance between TM1254 and members
      of the haloacid dehalogenase (HAD) hydrolase family.

PMID- 20054116
TI  - Structure of dihydrodipicolinate synthase from Methanocaldococcus jannaschii.
AB  - In bacteria and plants, dihydrodipicolinate synthase (DHDPS) plays a key role in
      the (S)-lysine biosynthesis pathway. DHDPS catalyzes the first step of the
      condensation of (S)-aspartate-beta-semialdehyde and pyruvate to form an unstable
      compound, (4S)-4-hydroxy-2,3,4,5-tetrahydro-(2S)-dipicolinic acid. The activity
      of DHDPS is allosterically regulated by (S)-lysine, a feedback inhibitor. The
      crystal structure of DHDPS from Methanocaldococcus jannaschii (MjDHDPS) was
      solved by the molecular-replacement method and was refined to 2.2 A resolution.
      The structure revealed that MjDHDPS forms a functional homotetramer, as also
      observed in Escherichia coli DHDPS, Thermotoga maritima DHDPS and Bacillus
      anthracis DHDPS. The binding-site region of MjDHDPS is essentially similar to
      those found in other known DHDPS structures.

PMID- 20054117
TI  - Structure of glyceraldehyde-3-phosphate dehydrogenase from the archaeal
      hyperthermophile Methanocaldococcus jannaschii.
AB  - The X-ray crystal structure of glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      from the hyperthermophilic archaeon Methanocaldococcus jannaschii (Mj-GAPDH) was
      determined to 1.81 A resolution. The crystal belonged to space group C222(1),
      with unit-cell parameters a = 83.4, b = 152.0, c = 118.6 A. The structure was
      solved by molecular replacement and was refined to a final R factor of 17.1%
      (R(free) = 19.8%). The final structure included the cofactor NADP(+) at the
      nucleotide-binding site and featured unoccupied inorganic and substrate phosphate
      binding sites. A comparison with GAPDH structures from mesophilic sources
      suggested that Mj-GAPDH is stabilized by extensive electrostatic interactions
      between the C-terminal alpha-helices and various distal loop regions, which are
      likely to contribute to thermal stability. The key phosphate-binding residues in
      the active site of Mj-GAPDH are conserved in other archaeal GAPDH proteins. These
      residues undergo a conformational shift in response to occupancy of the inorganic
      phosphate site.

PMID- 20054118
TI  - Structure of putative 4-amino-4-deoxychorismate lyase from Thermus thermophilus
      HB8.
AB  - The pyridoxal 5'-phosphate-dependent enzyme 4-amino-4-deoxychorismate lyase
      converts 4-amino-4-deoxychorismate to p-aminobenzoate and pyruvate in one of the
      crucial steps in the folate-biosynthesis pathway. The primary structure of the
      hypothetical protein TTHA0621 from Thermus thermophilus HB8 suggests that
      TTHA0621 is a putative 4-amino-4-deoxychorismate lyase. Here, the crystal
      structure of TTHA0621 is reported at 1.93 A resolution. The asymmetric unit
      contained four NCS molecules related by 222 noncrystallographic symmetry, in
      which the formation of intact dimers may be functionally important. The cofactor
      pyridoxal 5'-phosphate (PLP) binds to the protein in the large cleft formed by
      the N-terminal and C-terminal domains of TTHA0621. The high structural similarity
      and the conservation of the functional residues in the catalytic region compared
      with 4-amino-4-deoxychorismate lyase (PabC; EC 4.1.3.38) from Escherichia coli
      suggest that the TTHA0621 protein may also possess 4-amino-4-deoxychorismate
      lyase activity.

PMID- 20054119
TI  - Crystallization and X-ray structure of cold-shock protein E from Salmonella
      typhimurium.
AB  - In prokaryotic organisms, cold shock triggers the production of a small highly
      conserved family of cold-shock proteins (CSPs). CSPs have been well studied
      structurally and functionally in Escherichia coli and Bacillus subtilis, but
      Salmonella typhimurium CSPs remain relatively uncharacterized. In S. typhimurium,
      six homologous CSPs have been identified: StCspA-E and StCspH. The crystal
      structure of cold-shock protein E from S. typhimurium (StCspE) has been
      determined at 1.1 A resolution and has an R factor of 0.203 after refinement. The
      three-dimensional structure is similar to those of previously determined CSPs and
      is composed of five antiparallel beta-strands forming a classic OB fold/five
      stranded beta-barrel. This first structure of a CSP from S. typhimurium provides
      new insight into the cold-shock response of this bacterium.

PMID- 20054120
TI  - Structure of human glycolate oxidase in complex with the inhibitor 4-carboxy-5
      [(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole.
AB  - Glycolate oxidase, a peroxisomal flavoenzyme, generates glyoxylate at the expense
      of oxygen. When the normal metabolism of glyoxylate is impaired by the mutations
      that are responsible for the genetic diseases hyperoxaluria types 1 and 2,
      glyoxylate yields oxalate, which forms insoluble calcium deposits, particularly
      in the kidneys. Glycolate oxidase could thus be an interesting therapeutic
      target. The crystal structure of human glycolate oxidase (hGOX) in complex with 4
      carboxy-5-[(4-chlorophenyl)sulfanyl]-1,2,3-thiadiazole (CCPST) has been
      determined at 2.8 A resolution. The inhibitor heteroatoms interact with five
      active-site residues that have been implicated in catalysis in homologous
      flavodehydrogenases of L-2-hydroxy acids. In addition, the chlorophenyl
      substituent is surrounded by nonconserved hydrophobic residues. The present study
      highlights the role of mobility in ligand binding by glycolate oxidase. In
      addition, it pinpoints several structural differences between members of the
      highly conserved family of flavodehydrogenases of L-2-hydroxy acids.

PMID- 20054121
TI  - Structure of the first PDZ domain of human PSD-93.
AB  - The crystal structure of the PDZ1 domain of human PSD-93 has been determined to
      2.0 A resolution. The PDZ1 domain forms a crystallographic trimer that is also
      predicted to be stable in solution. The main contributions to the stabilization
      of the trimer seem to arise from interactions involving the PDZ1-PDZ2 linker
      region at the extreme C-terminus of PDZ1, implying that the oligomerization that
      is observed is not of biological significance in full-length PSD-93. Comparison
      of the structures of the binding cleft of PSD-93 PDZ1 with the previously
      reported structures of PSD-93 PDZ2 and PDZ3 as well as of the closely related
      human PSD-95 PDZ1 shows that they are very similar in terms of amino-acid
      composition. However, the cleft is significantly narrower in PSD-95. This could
      be part of the basis of peptide selectivity between PSD-93 PDZ1 and PSD-95 PDZ1.

PMID- 20054122
TI  - The high-resolution structure of the extracellular domain of human CD69 using a
      novel polymer.
AB  - The structure of the extracellular domain of human CD69 has been determined by
      single-crystal X-ray diffraction. The structure refined to 1.37 A resolution
      provides further details of the overall structure and the asymmetric interface
      between the monomers in the native dimer. The protein was crystallized using
      di[poly(ethylene glycol)] adipate, which also served as a cryoprotectant. This is
      the first report of a crystal structure determined using crystals grown with this
      polymer.

PMID- 20054123
TI  - Preliminary crystallographic analysis of mouse Elf3 C-terminal DNA-binding domain
      in complex with type II TGF-beta receptor promoter DNA.
AB  - Ets proteins are transcription factors that activate or repress the expression of
      genes that are involved in various biological processes, including cellular
      proliferation, differentiation, development, transformation and apoptosis. Like
      other Ets-family members, Elf3 functions as a sequence-specific DNA-binding
      transcriptional factor. A mouse Elf3 C-terminal fragment (amino-acid residues 269
      371) containing the DNA-binding domain has been crystallized in complex with
      mouse type II TGF-beta receptor promoter (TbetaR-II) DNA. The crystals belonged
      to space group P2(1)2(1)2(1), with unit-cell parameters a = 42.66, b = 52, c =
      99.78 A, and diffracted to a resolution of 2.2 A.

PMID- 20054124
TI  - Crystallization and preliminary X-ray diffraction studies of the carbohydrate
      recognition domain of SIGN-R1, a receptor for microbial polysaccharides and
      sialylated antibody on splenic marginal zone macrophages.
AB  - SIGN-R1, or CD209b, is a mouse C-type lectin receptor that is expressed at high
      levels on macrophages in lymphoid tissues, especially within the marginal zone of
      the spleen. SIGN-R1 can bind and mediate the uptake of various microbial
      polysaccharides, including dextrans, lipopolysaccharides and pneumococcal
      capsular polysaccharides. It has been shown that SIGN-R1 mediates the clearance
      of encapsulated pneumococcus, complement fixation via binding C1q independent of
      antibody and innate resistance to pneumococcal infection. Recently, SIGN-R1 has
      also been demonstrated to bind sialylated antibody and mediate its activity to
      suppress autoimmunity. The carbohydrate-recognition domain (CRD) of SIGN-R1 has
      been cloned and overexpressed in a soluble secretory form in mammalian Chinese
      hamster ovary (CHO) cells. The CRD protein of SIGN-R1 was purified from CHO cell
      culture supernatant and concentrated for crystallization using the hanging-drop
      vapour-diffusion method at 291 K. Crystals grew from a mixture of 2 M ammonium
      sulfate in 0.1 M bis-tris pH 5.5. Single crystals, which belonged to the
      monoclinic space group C2 with unit-cell parameters a = 146.72, b = 92.77, c =
      77.06 A, beta = 121.66 degrees , allowed the collection of a full X-ray data set
      to a maximum resolution of 1.87 A.

PMID- 20054125
TI  - Purification, crystallization and preliminary X-ray analysis of a deletion mutant
      of a major buckwheat allergen.
AB  - A 16 kDa buckwheat protein (BWp16) is a major allergen responsible for immediate
      hypersensitivity reactions including anaphylaxis. A deletion mutant of BWp16
      (rBWp16DeltaN) was overproduced and purified and was shown to be immunologically
      active. A three-wavelength MAD data set was collected from a crystal of
      selenomethionine-labelled rBWp16DeltaN. The crystal belonged to the triclinic
      space group P1, with unit-cell parameters a = 28.39, b = 31.54, c = 32.20 A,
      alpha = 111.92, beta = 108.91, gamma = 98.74 degrees . One monomer was expected
      to be present in the asymmetric unit based on the calculated Matthews coefficient
      of 1.76 A(3) Da(-1).

PMID- 20054126
TI  - Expression, crystallization and preliminary X-ray diffraction analysis of a
      modification subunit of a putative type I restriction enzyme from Vibrio
      vulnificus YJ016.
AB  - Modification (HsdM) and specificity (HsdS) subunits are constituents of an active
      methyltransferase (MTase) of multifunctional type I restriction enzymes. To
      provide a molecular background on HsdM, a putative hsdM gene from Vibrio
      vulnificus YJ016 (HsdM_Vv) was cloned and the expressed protein was purified and
      crystallized from 22%(w/v) polyethylene glycol 8000, 0.02 M imidazole pH 7.5 and
      5 mM beta-mercaptoethanol. Diffraction data were collected to 1.86 A resolution
      using synchrotron radiation. The crystal belonged to the tetragonal space group
      P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 78.9, c = 165.8 A.
      With one molecule in the asymmetric unit, the crystal volume per unit protein
      weight was 2.12 A(3) Da(-1), with a solvent content of 42%.

PMID- 20054127
TI  - Crystallization of selenomethionyl exo-beta-1,3-galactanase from the
      basidiomycete Phanerochaete chrysosporium.
AB  - Exo-beta-1,3-galactanase from Phanerochaete chrysosporium (Pc1,3Gal43A) consists
      of a glycoside hydrolase family 43 catalytic domain and a substrate-binding
      domain that belongs to carbohydrate-binding module family 35. It catalyzes the
      hydrolysis of beta-1,3-galactan, which is the backbone of the arabinogalactan
      proteins; the C-terminal carbohydrate-binding module family 35 domain increases
      the local concentration of the enzyme around beta-1,3-galactan by its high
      affinity for the substrate. To enable phase determination using the
      multiwavelength anomalous dispersion method, selenomethionyl Pc1,3Gal43A was
      crystallized at 298 K using the hanging-drop vapour-diffusion method. The
      presence of selenium in the crystals was confirmed from the X-ray absorption
      spectrum. The crystals belonged to space group P2(1) and diffracted to 1.8 A
      resolution.

PMID- 20054128
TI  - The taming of small heat-shock proteins: crystallization of the alpha-crystallin
      domain from human Hsp27.
AB  - Small heat-shock proteins (sHsps) are ubiquitous molecular chaperones. sHsps
      function as homooligomers or heterooligomers that are prone to subunit exchange
      and structural plasticity. Here, a procedure for obtaining diffraction-quality
      crystals of the alpha-crystallin domain of human Hsp27 is presented. Initially,
      limited proteolysis was used to delineate the corresponding stable fragment
      (residues 90-171). This fragment could be crystallized, but examination of the
      crystals using X-rays indicated partial disorder. The surface-entropy reduction
      approach was applied to ameliorate the crystal quality. Consequently, a double
      mutant E125A/E126A of the 90-171 fragment yielded well ordered crystals that
      diffracted to 2.0 A resolution.

PMID- 20054129
TI  - Purification, crystallization and preliminary X-ray analysis of the PCNA2-PCNA3
      complex from Sulfolobus tokodaii strain 7.
AB  - Crenarchaeal PCNA is known to consist of three subunits (PCNA1, PCNA2 and PCNA3)
      that form a heterotrimer (PCNA123). Recently, another heterotrimeric PCNA
      composed of only PCNA2 and PCNA3 was identified in Sulfolobus tokodaii strain 7
      (stoPCNAs). In this study, the purified stoPCNA2-stoPCNA3 complex was
      crystallized by hanging-drop vapour diffusion. The crystals obtained belonged to
      the orthorhombic space groups I222 and P2(1)2(1)2, with unit-cell parameters a =
      91.1, b = 111.8, c = 170.9 A and a = 91.1, b = 160.6, c = 116.6 A, respectively.
      X-ray diffraction data sets were collected to 2.90 A resolution for the I222
      crystals and to 2.80 A resolution for the P2(1)2(1)2 crystals.

PMID- 20054130
TI  - Crystallization and preliminary X-ray diffraction studies of FAD synthetase from
      Corynebacterium ammoniagenes.
AB  - FAD synthetase from Corynebacterium ammoniagenes (CaFADS), a prokaryotic
      bifunctional enzyme that catalyses the phosphorylation of riboflavin as well as
      the adenylylation of FMN, has been crystallized using the hanging-drop vapour
      diffusion method at 277 K. Diffraction-quality cubic crystals of native and
      selenomethionine-labelled (SeMet-CaFADS) protein belonged to the cubic space
      group P2(1)3, with unit-cell parameters a = b = c = 133.47 A and a = b = c =
      133.40 A, respectively. Data sets for native and SeMet-containing crystals were
      collected to 1.95 and 2.42 A resolution, respectively.

PMID- 20054131
TI  - Preliminary crystallographic studies of purine nucleoside phosphorylase from the
      cariogenic pathogen Streptococcus mutans.
AB  - The punA gene of the cariogenic pathogen Streptococcus mutans encodes purine
      nucleoside phosphorylase (PNP), which is a pivotal enzyme in the nucleotide
      salvage pathway, catalyzing the phosphorolysis of purine nucleosides to generate
      purine bases and alpha-ribose 1-phosphate. In the present work, the PNP protein
      was expressed in Escherichia coli strain BL21 (DE3) in a soluble form at a high
      level. After purification of the PNP enzyme, the protein was crystallized using
      the sitting-drop vapour-diffusion technique; the crystals diffracted to 1.6 A
      resolution at best. The crystals belonged to space group H3, with unit-cell
      parameters a = b = 113.0, c = 60.1 A.

PMID- 20054132
TI  - Crystallization and preliminary X-ray analysis of a monomeric mutant of Azami
      Green (mAG), an Aequorea victoria green fluorescent protein-like green-emitting
      fluorescent protein from the stony coral Galaxea fascicularis.
AB  - Monomeric Azami-Green (mAG) from the stony coral Galaxea fascicularis is the
      first monomeric green-emitting fluorescent protein that is not a derivative of
      Aequorea victoria green fluorescent protein (avGFP). mAG and avGFP are 27%
      identical in amino-acid sequence. Diffraction-quality crystals of recombinant mAG
      were obtained by the sitting-drop vapour-diffusion method using PEG 3350 as the
      precipitant. The mAG crystal diffracted X-rays to 2.20 A resolution on beamline
      AR-NW12A at the Photon Factory (Tsukuba, Japan). The crystal belonged to space
      group P1, with unit-cell parameters a = 41.78, b = 51.72, c = 52.89 A, alpha =
      90.96, beta = 103.41, gamma = 101.79 degrees. The Matthews coefficient (V(M) =
      2.10 A(3) Da(-1)) indicated that the crystal contained two mAG molecules per
      asymmetric unit.

PMID- 20054133
TI  - Crystallization and preliminary X-ray crystallographic analysis of a new crystal
      form of hydroxylamine oxidoreductase from Nitrosomonas europaea.
AB  - Hydroxylamine oxidoreductase (HAO) from Nitrosomonas europaea is a homotrimeric
      protein that catalyzes the oxidation of hydroxylamine to nitrite. Each monomer,
      with a molecular weight of 67.1 kDa, contains seven c-type hemes and one heme
      P460, the porphyrin ring of which is covalently linked to a tyrosine residue from
      an adjacent subunit. HAO was first crystallized and structurally characterized at
      a resolution of 2.8 A in 1997. The structure was solved in space group P6(3) and
      suffered from merohedral twinning. Here, a crystallization procedure is presented
      that yielded untwinned crystals belonging to space group P2(1)2(1)2, which
      diffracted to 2.25 A resolution and contained one trimer in the asymmetric unit.
      The unit-cell parameters were a = 140.7, b = 142.6, c = 107.4 A.

PMID- 20054134
TI  - Crystallization and preliminary X-ray analysis of neoagarobiose hydrolase from
      Saccharophagus degradans 2-40.
AB  - Many agarolytic bacteria degrade agar polysaccharide into the disaccharide unit
      neoagarobiose [O-3,6-anhydro-alpha-L-galactopyranosyl-(1-->3)-D-galactose] using
      various beta-agarases. Neoagarobiose hydrolase is an enzyme that acts on the
      alpha-1,3 linkage in neoagarobiose to yield D-galactose and 3,6-anhydro-L
      galactose. This activity is essential in both the metabolism of agar by
      agarolytic bacteria and the production of fermentable sugars from agar biomass
      for bioenergy production. Neoagarobiose hydrolase from the marine bacterium
      Saccharophagus degradans 2-40 was overexpressed in Escherichia coli and
      crystallized in the monoclinic space group C2, with unit-cell parameters a =
      129.83, b = 76.81, c = 90.11 A, beta = 101.86 degrees . The crystals diffracted
      to 1.98 A resolution and possibly contains two molecules in the asymmetric unit.

PMID- 20054135
TI  - Purification, crystallization and initial X-ray diffraction study of human REV7
      in complex with a REV3 fragment.
AB  - REV7 is involved in various cellular functions including DNA replication, signal
      transduction and cell-cycle regulation. In DNA replication, REV7 interacts with
      REV3 and forms DNA polymerase zeta, which plays a central role in error-prone DNA
      synthesis. REV3 is a catalytic subunit and its activity is stimulated by REV7. To
      clarify the structural basis of the interaction between REV7 and REV3, human REV7
      was crystallized in complex with a REV3 fragment. Two crystal forms were
      obtained. Crystal forms I and II belonged to space groups P2(1), with unit-cell
      parameters a = 43.8, b = 50.0, c = 107.3 A, beta = 96.9 degrees , and P4(1)2(1)2
      or P4(3)2(1)2, with unit-cell parameters a = b = 76.6, c = 118.4 A, respectively.

PMID- 20054136
TI  - Crystallization and preliminary X-ray crystallographic analysis of blood
      coagulation factor V-activating proteinase (RVV-V) from Russell's viper venom.
AB  - Russell's viper venom blood coagulation factor V activator (RVV-V) is a thrombin
      like serine proteinase that specifically activates factor V by cleaving a single
      peptide bond between Arg1545 and Ser1546. Activated factor V combines with
      activated factor X produced by the enzyme RVV-X in the venom to form the
      prothombinase complex, which can induce disseminated intravascular coagulopathy
      in envenomated animals. In the current study, RVV-V was crystallized in order to
      attempt to understand its substrate specificity for factor V. Four distinct
      crystal forms of RVV-V were obtained using the sitting-drop vapour-diffusion
      method and diffraction data sets were collected on SPring-8 beamlines. The best
      crystal of RVV-V generated data sets to 1.9 A resolution.

PMID- 20054137
TI  - Crystallization and preliminary crystallographic characterization of glutamine
      synthetase from Medicago truncatula.
AB  - The condensation of ammonium and glutamate into glutamine catalyzed by glutamine
      synthetase (GS) is a fundamental step in nitrogen metabolism in all kingdoms of
      life. In plants, this is preceded by the reduction of inorganic nitrogen to an
      ammonium ion and therefore effectively articulates nitrogen fixation and
      metabolism. Although the three-dimensional structure of the dodecameric bacterial
      GS was determined quite some time ago, the quaternary architecture of the plant
      enzyme has long been assumed to be octameric, mostly on the basis of low
      resolution electron-microscopy studies. Recently, the crystallographic structure
      of a monocotyledonous plant GS was reported that revealed a homodecameric
      organization. In order to unambiguously establish the quaternary architecture of
      GS from dicotyledonous plants, GS1a from the model legume Medicago truncatula was
      overexpressed, purified and crystallized. The collection of synchrotron
      diffraction data to 2.35 A resolution allowed the determination of the three
      dimensional structure of this enzyme by molecular replacement.

PMID- 20054138
TI  - Expression, purification, crystallization and preliminary X-ray analysis of
      maleylacetate reductase from Burkholderia sp. strain SJ98.
AB  - Maleylacetate reductase (EC 1.3.1.32) is an important enzyme that is involved in
      the degradation pathway of aromatic compounds and catalyzes the reduction of
      maleylacetate to 3-oxoadipate. The gene pnpD encoding maleylacetate reductase in
      Burkholderia sp. strain SJ98 was cloned, expressed in Escherichia coli and
      purified by affinity chromatography. The enzyme was crystallized in both native
      and SeMet-derivative forms by the sitting-drop vapour-diffusion method using PEG
      3350 as a precipitant at 293 K. The crystals belonged to space group P2(1)2(1)2,
      with unit-cell parameters a = 72.91, b = 85.94, c = 53.07 A. X-ray diffraction
      data for the native and SeMet-derivative crystal were collected to 2.7 and 2.9 A
      resolution, respectively.

PMID- 20054139
TI  - Purification, crystallization and preliminary crystallographic analysis of a
      thermostable endonuclease IV from Thermotoga maritima.
AB  - The DNA-repair enzyme endonuclease IV from the thermophilic bacterium Thermotoga
      maritima MSB8 (reference sequence NC_000853) has been expressed in Escherichia
      coli and crystallized for X-ray analysis. T. maritima endonuclease IV is a 287
      amino-acid protein with 32% sequence identity to E. coli endonuclease IV. The
      protein was purified to homogeneity and was crystallized using the sitting-drop
      vapor-diffusion method. The protein crystallized in space group P6(1), with one
      biological molecule in the asymmetric unit, corresponding to a Matthews
      coefficient of 2.39 A(3) Da(-1) and 47% solvent content. The unit-cell parameters
      of the crystals were a = b = 123.2, c = 35.6 A. Microseeding and further
      optimization yielded crystals with an X-ray diffraction limit of 2.36 A. A single
      70 degrees data set was collected and processed, resulting in an overall R(merge)
      and a completeness of 9.5% and 99.3%, respectively.

PMID- 20054140
TI  - Lamellar body exocytosis by cell stretch or purinergic stimulation: possible
      physiological roles, messengers and mechanisms.
AB  - A major function of the pulmonary alveolar type II cell is the secretion of
      surfactant, a lipoprotein-like substance, via exocytosis of secretory vesicles
      termed lamellar bodies (LBs). The process of surfactant secretion is remarkable
      in several aspects, considering stimulus-delayed fusion activity, poor solubility
      of vesicle contents, long hemifusion lifetimes, slow fusion pore expansion and
      active, actin-driven content release. Cell stretch as well as P2Y(2) receptor
      stimulation by extracellular ATP are considered the most potent stimuli for LB
      exocytosis. For both stimuli, elevation of the cytoplasmic Ca(2+) concentration
      [Ca(2+)](c) is a key step. This review summarizes possible physiological roles
      and pathways of stretch- or ATP-induced surfactant secretion and discusses
      molecular mechanisms controlling the pre-, hemi- and postfusion phase, in
      comparison with neuroendocrine release mechanisms.

PMID- 20054142
TI  - The closer we look the more we see? Quantitative microscopic analysis of the
      pulmonary surfactant system.
AB  - The surfactant system of the lung has essential biophysical and immunomodulatory
      functions. Only at the electron microscopic level does surfactant reveal its
      morphological complexity--and beauty. Therefore, morphological tools are
      indispensible to characterize the surfactant system in health and disease.
      Stereology provides the gold standard for obtaining quantitative (morphometric)
      data in microscopy. The combination of microscopy and stereology allows for
      qualitative and quantitative analysis of the intraalveolar as well as the
      intracellular surfactant pool, both in its preserved microorganization and
      localization within the lung. Surfactant-producing alveolar epithelial type II
      cells can be counted and sampled for size estimation with physical disectors at a
      high magnification light microscopic level. The number of their surfactant
      storing lamellar bodies can be estimated using physical disectors at the electron
      microscopic level. Electron tomography allows for high resolution 3D
      visualization of lamellar body fusion pores. Intraalveolar surfactant subtypes
      can be quantitated in situ, thus reflecting the functional state of the
      intraalveolar surfactant pool. By immunoelectron microscopy, surfactant protein
      distribution can be analyzed. These methods allow for a comprehensive
      quantitative analysis of surfactant (ultra-)structure. Here, we give an overview
      on the analysis of the normal and disordered surfactant system by electron
      microscopy and stereology.

PMID- 20054141
TI  - Pulmonary surfactant: an immunological perspective.
AB  - Pulmonary surfactant has two crucial roles in respiratory function; first, as a
      biophysical entity it reduces surface tension at the air water interface,
      facilitating gas exchange and alveolar stability during breathing, and, second,
      as an innate component of the lung's immune system it helps maintain sterility
      and balance immune reactions in the distal airways. Pulmonary surfactant consists
      of 90% lipids and 10% protein. There are four surfactant proteins named SP-A, SP
      B, SP-C, and SP-D; their distinct interactions with surfactant phospholipids are
      necessary for the ultra-structural organization, stability, metabolism, and
      lowering of surface tension. In addition, SP-A and SP-D bind pathogens, inflict
      damage to microbial membranes, and regulate microbial phagocytosis and activation
      or deactivation of inflammatory responses by alveolar macrophages. SP-A and SP-D,
      also known as pulmonary collectins, mediate microbial phagocytosis via SP-A and
      SP-D receptors and the coordinated induction of other innate receptors. Several
      receptors (SP-R210, CD91/calreticulin, SIRPalpha, and toll-like receptors)
      mediate the immunological functions of SP-A and SP-D. However, accumulating
      evidence indicate that SP-B and SP-C and one or more lipid constituents of
      surfactant share similar immuno-regulatory properties as SP-A and SP-D. The
      present review discusses current knowledge on the interaction of surfactant with
      lung innate host defense.

PMID- 20054144
TI  - The great big alveolar TI cell: evolving concepts and paradigms.
AB  - Pulmonary alveolar type I cells (TI cell) are very large (approximately 5400
      microm(2) in surface area) squamous cells that cover more than 98% of the
      internal surface area of rodent lungs. In the past, TI cells were believed to
      serve only passive barrier functions, with no active functional properties in the
      lung. The fairly recent development of methods to isolate TI cells has permitted
      investigation of functions of this cell type for the first time. Resolvable by
      electron microscopy, TI cells contain microvilli and organelles typically
      associated with metabolic functions, such as mitochondria, abundant smooth and
      rough endoplasmic reticulum and Golgi apparatus. TI cells contain the molecular
      machinery necessary for ion transport and take up Na(+), K(+), and Cl(-), from
      which one can infer that it is likely that they play a role in ion and fluid
      transport in vivo. Because the abundance/microm(2) of highly selective Na(+)
      channels (HSC channels, consisting of all three ENaC subunits) is the same in TI
      and TII cells and because TI cells cover the majority of the lung internal
      surface, TI cells may play the major role in bulk transport of Na(+). In vitro,
      TI cells can proliferate and exhibit phenotypic plasticity, raising the question
      of whether this cell type may play a role in development and lung repair after
      injury. From gene expression analysis of TI cells, one can infer a variety of
      other possible functions for TI cells. The development of techniques to
      administer transgenes specifically to TI cells will permit direct study of this
      cell type in vivo.

PMID- 20054143
TI  - P63 (CKAP4) as an SP-A receptor: implications for surfactant turnover.
AB  - Surfactant protein-A (SP-A) plays an important role in the clearance of
      surfactant from the lung alveolar space and in the regulation of surfactant
      secretion and uptake by type II pneumocytes in culture. Two pathways are
      important for the endocytosis of surfactant by type II cells and the intact lung,
      a receptor-mediated clathrin-dependent pathway and a non-clathrin, actin-mediated
      pathway. The critical role of the clathrin/receptor-mediated pathway in normal
      mice is supported by the finding that SP-A gene-targeted mice use the actin
      dependent pathway to maintain normal clearance of surfactant. Addition of SP-A to
      the surfactant of the SP-A null mice "rescued" the phenotype, further emphasizing
      the essential role of the SP-A/receptor-mediated process in surfactant turnover.
      This review presents an overview of the structure of SP-A and its function in
      surfactant turnover. The evidence that the interaction of SP-A with type II cells
      is a receptor-mediated process is presented. A newly identified receptor for SP
      A, P63/CKAP4, is described in detail, with elucidation of the specific structural
      features of this 63 kDa, nonglycosylated, highly coiled, transmembrane protein.
      The compelling evidence that P63 functions as a receptor for SP-A on type II
      cells is summarized. Regulation of P63 receptor density on the surface of
      pneumocytes may be a novel approach for the regulation of surfactant homeostasis
      by the lung.

PMID- 20054145
TI  - Importance of ENaC-mediated sodium transport in alveolar fluid clearance using
      genetically-engineered mice.
AB  - The lung possesses specific transport systems that intra- and extracellularly
      maintain salt and fluid balance necessary for its function. At birth, the lungs
      rapidly transform into a fluid (Na(+))-absorbing organ to enable efficient gas
      exchange. Alveolar fluid clearance, which mainly depends on sodium transport in
      alveolar epithelial cells, is an important mechanism by which excess water in the
      alveoli is reabsorbed during the resolution of pulmonary edema. In this review,
      we will focus and summarize on the role of ENaC in alveolar lung liquid clearance
      and discuss recent data from mouse models with altered activity of epithelial
      sodium channel function in the lung, and more specifically in alveolar fluid
      clearance. Recent data studying mice with hyperactivity of ENaC or mice with
      reduced ENaC activity clearly illustrate the impaired lung fluid clearance in
      these adult mice. Further understanding of the physiological role of ENaC and its
      regulatory proteins implicated in salt and water balance in the alveolar cells
      may therefore help to develop new therapeutic strategies to improve gas exchange
      in pulmonary edema.

PMID- 20054146
TI  - Experimental models to study cell wounding and repair.
AB  - Cell wounding, that is a loss of plasma membrane integrity, is a common everyday
      occurrence in load bearing organs such as muscle, skin, and bone. In general,
      these injuries trigger adaptive responses to either restore homeostasis or to
      protect the cells from further damage. The ability to restore plasma membrane
      integrity after injury is critical for cell survival and all cells possess a
      means to do so. However, the probability of plasma membrane wound repair depends
      on the cell type, as well as the size and nature of the lesion. Several in vitro
      experimental models of cell injury have been developed to simulate specific
      stresses cells experience in vivo. Motivated by our interest in studying the
      mechanisms of cell injury and repair relevant to ventilator associated lung
      injury, we review some of the most frequently used in vitro experimental models
      of cell wounding and present some new data pertaining to alveolar epithelium.

PMID- 20054147
TI  - Plasma membrane trafficking in alveolar type II cells.
AB  - Alveolar type II (ATII) cells produce surfactant and release it into the alveolar
      space via exocytosis of lamellar bodies (LBs). On the other hand, various forms
      of endocytosis take place, enabling the recycling of surfactant as well as of
      integral membrane proteins to the LB. Here we investigated the trafficking of
      protein and lipid components of plasma membrane between the plasma and limiting
      LB membrane by over-expressing lysosomal associated membrane protein 3 fused to
      green fluorescence protein (LAMP-3-GFP) and farnesylated DsRed (DsRed-Farn). LAMP
      3-GFP was homogenously distributed over the entire limiting LB membrane, whereas
      DsRed-Farn predominantly accumulated at the plasma membrane. However, in a minor
      LB fraction, DsRed-Farn was also found in discrete domains at its limiting
      membrane. Upon stimulation of ATII cells with secretagogues, the area of DsRed
      Farn domains on LB surfaces increased 2 to 4 fold within 20 minutes of
      stimulation. This increase remained unaffected by phenylarsine oxide, an
      inhibitor of clathrin-dependent endocytosis, but was almost abolished by filipin
      and indomethacin, blockers of clathrin-independent endocytosis. It was also
      blocked by bafilomycin A1, wortmannin and LY294002, inhibitors of intra-cellular
      vesicular transport. We conclude that secretagogues facilitate the transport of
      plasma membrane components to LBs via a clathrin-independent vesicular transport
      pathway.

PMID- 20054148
TI  - 2-APB and capsazepine-induced Ca2+ influx stimulates clathrin-dependent
      endocytosis in alveolar epithelial cells.
AB  - Calcium as a second messenger influences many cellular and physiological
      processes. In lung, alveolar type II (ATII) cells sense mechanical stress and
      respond by Ca(2+) dependent release of surfactant, which is essential for
      respiratory function. Nevertheless, Ca(2+) signaling mechanisms in these cells-
      in particular Ca(2+) entry pathways are still poorly understood. Herein, we
      investigated pharmacological properties of non-voltage-gated Ca(2+) channel
      modulators in ATII and NCI-H441 cells and demonstrate that 2-Aminoethoxydiphenyl
      borinate (2-APB) and capsazepine (CPZ) activate Ca(2+) entry with
      pharmacologically distinguishable components. Surprisingly, 2-APB and CPZ
      activated clathrin dependent endocytosis in ATII and NCI-H441 cells, which was
      dependent on Ca(2+) entry. The internalized material accumulated in non-acidic
      granules distinct from surfactant containing lamellar bodies (LB). LB exocytosis
      was not observed under these conditions. Our study demonstrates that 2-APB/CPZ
      induces Ca(2+) entry which unlike ATP- or stretch-induced Ca(2+) entry in ATII
      cells does not activate exocytosis but an opposing endocytotic mechanism.

PMID- 20054149
TI  - T1alpha/podoplanin shows raft-associated distribution in mouse lung alveolar
      epithelial E10 cells.
AB  - AIMS: T1alpha/(podoplanin) is abundantly expressed in the alveolar epithelial
      type I cells (ATI) of rodent and human lungs. Caveolin-1 is a classical primary
      structural protein of plasmalemal invaginations, so-called caveolae, which
      represent specialized lipid rafts, and which are particularly abundant in ATI
      cells. The biological functions of T1alpha in the alveolar epithelium are
      unknown. Here we report on the characteristics of raft domains in the
      microplicae/microvillar protrusions of ATI cells, which contain T1alpha. METHODS:
      Detergent resistant membranes (DRMs) from cell lysates of the mouse epithelial
      ATI-like cell line E10 were prepared using different detergents followed by
      flotation in a sucrose gradient and tested by Western and dot blots with raft
      markers (caveolin-1, GM1) and nonraft markers (transferrin receptor, PDI and beta
      Cop). Immunocytochemistry was employed for the localization of T1alpha in E10
      cells and in situ in rat lungs. RESULTS: Our biochemical results showed that the
      solubility or insolubility of T1alpha and caveolin-1 differs in Triton X-100 and
      Lubrol WX, two distinct non-ionic detergents. Caveolin-1 was unsoluble in both
      detergents, whereas T1alpha was Triton X-100 soluble but Lubrol WX insoluble.
      Immunofluorescence double stainings revealed that both proteins were colocalized
      with GM1, while caveolin-1 and T1alpha were not colocalized in the plasma
      membrane. Cholesterol depletion modified the segregation of T1alpha in Lubrol WX
      DRMs. Cellular processes in ultrathin sections of cultured mouse E10 cells were
      immunogold positive. Immunoelectron microscopy (postembedding) of rat lung tissue
      revealed the preferential localization of T1alpha on apical microvillar
      protrusions of ATI cells. CONCLUSION: We conclude that T1alpha and caveolin-1 are
      located in distinct plasma membrane microdomains, which differ in their protein
      lipid interactions. The raft-associated distribution of T1alpha may have an
      impact on a specific, not yet clarified function of this protein in the alveolar
      epithelium.

PMID- 20054150
TI  - Cyclic stretch magnitude and duration affect rat alveolar epithelial gene
      expression.
AB  - Mechanical ventilation with large tidal volumes can increase lung alveolar
      permeability and initiate inflammatory responses; but the mechanisms that
      regulate ventilator-associated lung injury and inflammation remain unclear.
      Analysis of the genomic response of the lung has been performed in intact lungs
      ventilated at large tidal volumes. This study is the first to study the genomic
      response of cultured primary alveolar epithelial cells undergoing large and
      moderate physiologic cyclic stretch. Responses were dependent on stretch
      magnitude and duration. Genomic expression was validated for 5 genes of interest:
      Amphiregulin, Glutamate-Cysteine Ligase Catalytic subunit, Matrix
      Metalloproteinase 7, Protein Phosphatase 1 regulatory inhibitor subunit 10, and
      Serpine-1, and protein expression mirrored genomic responses. Differences between
      results reported from homogenized intact lungs and monolayers of alveolar
      epithelial cells with type-I like phenotype provide provocative evidence that the
      whole lung preparation may mask the response of individual cell types.

PMID- 20054151
TI  - Beta2-adrenergic stimulation blunts inhibition of epithelial ion transport by
      hypoxia of rat alveolar epithelial cells.
AB  - Hypoxia impairs alveolar fluid clearance by inhibition of Na(+) reabsorption, and
      also impairs beta(2) adrenergic signaling in alveolar epithelium. Since both are
      major rescue mechanisms preventing pulmonary edema, we studied whether acute and
      prolonged treatment with terbutaline would prevent hypoxic inhibition of ion
      transport. Short circuit currents (ISC) were measured on normoxic and hypoxic
      (1.5% O(2); 24h) primary rat alveolar type II (ATII) cells in absence and
      presence of terbutaline (1 to 100 microM, 24h). Control and pre-treated cells
      were stimulated acutely with terbutaline. Transepithelial transport was measured
      as short circuit current (ISC) in Ussing chambers. Terbutaline induced a rapid
      decrease ISC (-20%) followed by a slow raise. The transient change in ISC was not
      inhibited by amiloride but was prevented after Cl(-) depletion indicating a Cl(-)
      current. The slow increase after this transient was amiloride-sensitive
      indicating a Na(+) current. Total ISC, its amiloride-sensitive component, and the
      transient decrease upon terbutaline stimulation were decreased by hypoxia. 24h
      treatment with terbutaline stimulated these currents in normoxia and hypoxia,
      although stimulation was less in the latter. 24h treatment with terbutaline
      increased the capacity of Na(+)/K(+)-ATPase and ENaC as measured after
      permeabilization with amphotericin. These changes were not paralleled by altered
      mRNA expression. Acutely applied terbutaline induced a 4-fold increase in cAMP
      formation in normoxia; terbutaline-induced cAMP-formation was impaired by hypoxia
      (-20%). Pre-treatment with terbutaline for 24h decreased terbutaline-induced cAMP
      formation by 85%. Despite this desensitization, addition of terbutaline to
      terbutaline pre-treated cells caused a larger increase in Cl(-) and Na(+)
      transport both in normoxia and hypoxia than in non pre-treated cells. These
      results indicate that beta(2) adrenergic stimulation increased Na(+)- and Cl(-)
      transport in ATII cells even in hypoxia thus restoring normal reabsorption.

PMID- 20054152
TI  - Differential effects of hypoxic stress in alveolar epithelial cells and
      microvascular endothelial cells.
AB  - Under hypoxic conditions eukaryotic cells and tissues undergo adaptive responses
      involving glycolysis, angiogenesis, vasoconstriction and inflammation. The
      underlying molecular mechanisms are not yet fully elucidated and are most likely
      cell and tissue specific. In the lung, alveolar epithelial cells and
      microvascular endothelial cells are highly sensitive to hypoxia and together
      orchestrate a rapid and sustained adaptive response. We examined the effect of
      different oxygen tensions on cell viability, glucose metabolism, key
      transcription factors and signaling molecules, in alveolar epithelial cells
      (A549) and microvascular endothelial cells (HMEC-1). Both cell types tolerated
      hypoxia without detectable cell injury. Hypoxia induced glycolysis in both
      epithelial and microvascular endothelial cells, although A549 cells exhibited a
      higher rate of glucose consumption. The transcription factor CREB (cAMP response
      element binding protein) was activated with decreasing oxygen tensions in both
      cell types. This effect was again more marked in A549 cells, demonstrating
      epithelial cells to be more oxygen sensitive. Activating Transcription Factor 3
      (ATF-3) was heavily induced by hypoxia in A549 cells but not in HMEC-1 cells.
      Both cell types exhibited hypoxia induced secretion of VEGF and IL-6. Secretion
      of the vasoconstrictor endothelin-1 (ET1) was increased by hypoxia in HMEC-1
      cells but decreased in A549 cells. These data reveal that both cell types exhibit
      an adaptive response to hypoxia but alveolar epithelial cells are generally more
      sensitive. ET-1 was oppositely regulated by decreased oxygen tensions in the
      investigated cell types. The present study further elucidates the adaptive
      molecular mechanisms in pulmonary hypoxia and demonstrates cell specific
      responses.

PMID- 20054153
TI  - Functional characterization of a partial loss-of-function mutation of the
      epithelial sodium channel (ENaC) associated with atypical cystic fibrosis.
AB  - Loss-of-function mutations of the epithelial sodium channel (ENaC) may contribute
      to pulmonary symptoms resembling those of patients with atypical cystic fibrosis
      (CF). Recently, we identified a loss-of-function mutation in the alpha-subunit of
      ENaC (alphaF61L) in an atypical CF patient without mutations in CFTR. To
      investigate the functional effect of this mutation, we expressed human wild-type
      alpha beta gamma-ENaC or mutant alpha(F61L) beta gamma-ENaC in Xenopus laevis
      oocytes. The alphaF61L mutation reduced the ENaC mediated whole-cell currents by
      approximately 90%. In contrast, the mutation decreased channel surface expression
      only by approximately 40% and did not alter the single-channel conductance. These
      findings indicate that the major effect of the mutation is a reduction of the
      average channel open probability (P(o)). This was confirmed by experiments using
      the betaS520C mutant ENaC which can be converted to a channel with a P(o) of
      nearly one, and by experiments using chymotrypsin to proteolytically activate the
      channel. These experiments revealed that the mutation reduced the average P(o) of
      ENaC by approximately 75%. Na(+) self inhibition of the mutant channel was
      significantly enhanced, but the observed effect was too small to account for the
      large reduction in average channel P(o). The ENaC-activator S3969 partially
      rescued the loss-of-function phenotype of the alphaF61L mutation. We conclude
      that the alphaF61L mutation may contribute to respiratory symptoms in atypical CF
      patients.

PMID- 20054155
TI  - Welcome to OBESITY FACTS, the official journal of the European Association for
      the Study of Obesity (EASO)!

PMID- 20054154
TI  - Characterisation of cadmium chloride induced molecular and functional alterations
      in airway epithelial cells.
AB  - Epidemiological studies show that cadmium (Cd) exposure causes pulmonary damage,
      such as emphysema, pneumonitis, and lung cancer. However, the mechanisms leading
      to pulmonary toxicity are not yet fully elucidated. The aim of this study was to
      further investigate cadmium chloride (CdCl(2)) induced toxicity using Calu-3
      cells as an in vitro model of human bronchial epithelial cells. CdCl(2) induced
      effects following either apical or basolateral exposure were evaluated by Neutral
      Red Uptake (NRU), Trans-Epithelial Electrical Resistance (TEER), and alteration
      in Metallothionein 1X (MT1X), Heat shock protein 70 (HSP70), and Heme oxygenase 1
      (HMOX-1) genes. CdCl(2) exposure resulted in a collapse of barrier function and
      the induction of MT1X, HMOX-1 and HSP70 genes, prior to alterations in cell
      viability. These effects were more pronounced when the exposure was from the
      basolateral side. Co-administration of N-Acetylcysteine (NAC) exerted a strong
      protective effect against CdCl(2) induced barrier damage and stress related
      genes, while other antioxidants only attenuated CdCl(2) induced HSP70 and HMOX-1
      and showed no protective effect on the barrier collapse. These findings indicate
      that CdCl(2) exposure is likely to impair Calu-3 barrier function at non
      cytotoxic concentrations by a direct effect on adherens junction proteins. The
      protective effect of NAC against CdCl(2) induced MT1X, HSP70 and HMOX-1 genes,
      demonstrates an anti-oxidant effect of NAC in addition to Cd chelation.

PMID- 20054156
TI  - An EASO goal achieved! OBESITY FACTS launched as official journal of EASO.

PMID- 20054157
TI  - Peripheral metabolic effects of endocannabinoids and cannabinoid receptor
      blockade.
AB  - The endocannabinoid system consists of endogenous arachidonic acid derivates that
      activate cannabinoid receptors. The two most prominent endocannabinoids are
      anandamide and 2-arachidonoyl glycerol. In obesity, increased concentrations of
      circulating and tissue endocannabinoid levels have been described, suggesting
      increased activity of the endocannabinoid system. Increased availability of
      endocannabinoids in obesity may over-stimulate cannabinoid receptors. Blockade of
      cannabinoid type 1 (CB1) receptors was the only successful clinical development
      of an anti-obesity drug during the last decade. Whereas blockade of CB1 receptors
      acutely reduces food intake, the long-term effects on metabolic regulation are
      more likely mediated by peripheral actions in liver, skeletal muscle, adipose
      tissue, and the pancreas. Lipogenic effects of CB1 receptor signalling in liver
      and adipose tissue may contribute to regional adipose tissue expansion and
      insulin resistance in the fatty liver. The association of circulating 2
      arachidonoyl glycerol levels with decreased insulin sensitivity strongly suggests
      further exploration of the role of endocannabinoid signalling for insulin
      sensitivity in skeletal muscle, liver, and adipose tissue. A few studies have
      suggested a specific role for the regulation of adiponectin secretion from
      adipocytes by endocannabinoids, but that has to be confirmed by more experiments.
      Also, the potential role of CB1 receptor blockade for the stimulation of energy
      expenditure needs to be studied in the future. Despite the current discussion of
      safety issues of cannabinoid receptor blockade, these findings open a new and
      exciting perspective on endocannabinoids as regulators of body weight and
      metabolism.

PMID- 20054158
TI  - Primary prevention of childhood obesity: an interdisciplinary analysis.
AB  - The primary prevention of childhood obesity requires combined efforts by
      stakeholders at various societal levels, based on the knowledge from multiple
      disciplines. The goal of the present study was therefore to analyze current
      preventive approaches and delineate implications for future prevention research
      and practice by integrating knowledge from genetics, law, economics, psychology,
      and social ethics. Inconclusive evidence on the etiology of obesity, a complex,
      multifactorial condition, likely complicates prevention, leading to a lack of
      specificity regarding target groups, focus, and techniques. It is recommended to
      increase the specificity of prevention by explicitly considering risk factor
      evidence, including evidence on genetic factors. Because the institutional and
      legal framework of primary obesity prevention in children is insufficient in many
      countries, considering the risk factors for childhood obesity is also crucial for
      establishing a basis for legal regulations. Companies from sectors concerned with
      food intake and physical activity may be involved in preventive action, e.g., for
      initiating self-defeating sanctions. Long-term behavior change may be enhanced
      through the systematic application of behavior modification techniques within
      primary prevention programs. Overall, an interdisciplinary perspective furthers
      understanding of the complexity of this condition and can inform public health
      strategies on the primary prevention of childhood obesity.

PMID- 20054159
TI  - The German Working Group of Obesity in Childhood and Adolescence (AGA): improving
      the quality of care for overweight and obese children in Germany.
AB  - The Working Group of Obesity in Childhood and Adolescence (AGA) comprises
      scientists, clinicians, and therapists dealing with obesity in children and
      adolescents. More than 250 pediatricians, psychiatrics, dieticians, psychologists
      and sports therapists are integrated. On an international level, the AGA
      cooperates with the European Childhood Obesity Group and the International
      Obesity Taskforce (IOTF) for Childhood Obesity. The aims of the AGA are to
      initiate clinical and scientific studies, to join diagnostic, therapeutic and
      scientific centers, to improve the education, to support self-help groups, and to
      standardize diagnostic and therapeutic procedures in the field of obesity in
      childhood and adolescence. The milestones in the history of the AGA are the
      consensus process to define overweight and obesity in Germany, the development of
      guidelines for diagnostic procedures and treatment of obesity in childhood and
      adolescence, the determination of all therapy centers for obese children and
      adolescents in Germany, the development of a PC software (APV) to document
      longitudinally diagnostic and therapeutic procedures as well as outcomes by a
      quality management program, the certification of therapeutic institutions, and
      the implementation of prevention and treatment studies. As effect of these
      initiatives, the quality of care in overweight children has been improved in the
      last years. For example, the APV quality program demonstrated an increase of
      diagnostic procedures such as blood pressure measurement in the last 4 years.

PMID- 20054160
TI  - Polygenic obesity in humans.
AB  - The molecular genetic analysis of obesity has led to the identification of a
      limited number of confirmed major genes. While such major genes have a clear
      influence on the development of the phenotype, the underlying mutations are
      however (extremely) infrequent and thus of minor clinical importance only. The
      genetic predisposition to obesity must thus be polygenic; a number of such
      variants should be found in most obese subjects; however, these variants
      predisposing to obesity are also found in normal weight and even lean
      individuals. Therefore, a polygene can only be identified and validated by
      statistical analyses: the appropriate gene variant (allele) occurs more
      frequently in obese than in non-obese subjects. Each single polygene makes only a
      small contribution to the development of obesity. The 103Ile allele of the
      Val103Ile single nucleotide polymorphism (SNP) of the melanocortin-4 receptor
      gene (MC4R) was the first confirmed polygenetic variant with an influence on the
      body mass index (BMI); the more common Val103 allele is more frequent in obese
      individuals. As determined in a recent, large-scaled meta-analysis the effect
      size of this allele on mean BMI was approximately -0.5 kg/m(2). The first genome
      wide association study (GWA) for obesity, based on approximately 100,000 SNPs
      analyzed in families of the Framingham study, revealed that a SNP in the
      proximity of the insulin-induced gene 2 (INSIG2) was associated with obesity. The
      positive result was replicated in independent samples; however, some other study
      groups detected no association. Currently, a meta-analysis is ongoing; its result
      will contribute to the evaluation of the importance of the INSIG2 polymorphism in
      body weight regulation. SNP alleles in intron 1 of the fat mass and obesity
      associated gene (FTO) confer the most relevant polygenic effect on obesity. In
      the first GWA for extreme early onset obesity we substantiated that variation in
      FTO strongly contributes to early onset obesity.

PMID- 20054161
TI  - On the history of Fto.

PMID- 20054162
TI  - Postprandial triglyceride response in men: role of overweight, abdominal fat and
      nutrition.
AB  - OBJECTIVE: The study analyses i) the effect of overweight, waist circumference
      and dietary habits on postprandial (pp) triglyceride (TG) response and compares
      ii) pp TG response with fasting TG levels and iii) pp TG peak values with TG-AUC
      (area under curve) with respect to cardiometabolic risk assessment. METHODS: In
      100 men (44-68 years) body composition (air-displacement plethysmography),
      dietary habits, cardiometabolic risk and pp lipid metabolism (standardised lipid
      load) were assessed. A pp TG peak value of 260 mg/dl was used as a cut-off to
      classify TG normal- and high-responders. RESULTS: pp TG response had positive
      associations with BMI (r = 0.24; p < 0.05), fat mass (r = 0.28; p < 0.01), waist
      circumference (r = 0.33; p < 0.01), systolic blood pressure (r = 0.21; p < 0.05),
      fasting (r = 0.29; p < 0.01) and pp glucose (r = 0.40; p < 0.001), fasting (r =
      0.38; p < 0.001) and pp insulin levels (r = 0.46; p < 0.001), and inverse
      associations with HDL-C (r = -0.43; p < 0.001) and intake of dietary fibre (r = 
      0.31; p < 0.05). Fasting TG levels had a greater contribution to the variance in
      12 of 14 cardiometabolic risk factors compared to pp TG response. TG-AUC was
      highly correlated to cardiometabolic risk. CONCLUSION: Overweight, abdominal fat
      and a low intake of dietary fibre were determinants of increased pp TG response.
      Contrary to findings in younger normal-weight men, fasting TG levels had a
      stronger association with cardio metabolic risk compared to pp TG response. This
      might be explained by differences in fat mass.

PMID- 20054163
TI  - Interdisciplinary European guidelines on surgery of severe obesity.
AB  - In 2005, for the first time in European history, an extraordinary expert panel
      named BSCG (Bariatric Scientific Collaborative Group), was appointed through
      joint effort of the major European scientific societies which are active in the
      field of obesity management. Societies that constituted this panel were: IFSO -
      International Federation for the Surgery of Obesity, IFSO-EC - International
      Federation for the Surgery of Obesity - European Chapter, EASO - European
      Association for Study of Obesity, ECOG - European Childhood Obesity Group,
      together with the IOTF (International Obesity Task Force) which was represented
      during the completion process by its representative. The BSCG was composed not
      only of the top officers representing the respective scientific societies (four
      acting presidents, two past presidents, one honorary president, two executive
      directors), but was balanced with the presence of many other key opinion leaders
      in the field of obesity. The BSCG composition allowed the coverage of key
      disciplines in comprehensive obesity management, as well as reflecting European
      geographical and ethnic diversity. This joint BSCG expert panel convened several
      meetings which were entirely focused on guidelines creation, during the past 2
      years. There was a specific effort to develop clinical guidelines, which will
      reflect current knowledge, expertise and evidence based data on morbid obesity
      treatment.

PMID- 20054164
TI  - Steps to a leaner Europe - an initiative of the European union.

PMID- 20054165
TI  - Hypothalamic thyroid hormone in energy balance regulation.
AB  - Thyroid hormone has been known for decades as a hormone with profound effects on
      energy expenditure and ability to control weight. The regulation of energy
      expenditure by thyroid hormone primarily occurs via regulation of the activity,
      or expression, of uncoupling proteins in peripheral tissues. However,
      mechanistically this requires a signal from the brain to change circulating
      levels of thyroxine and thyroid hormone or increased sympathetic drive to
      peripheral tissues to alter local thyroid hormone levels via increased expression
      of type 2 deiodinase. However, little consideration has been given to the
      potential role and involvement of thyroid hormones action in the brain in the
      regulation of energy balance. Recent evidence implicates thyroid hormone as a
      shortterm signal of energy deficit imposed by starvation. Furthermore, thyroid
      hormone action within the hypothalamus is involved in adjusting long-term energy
      expenditure in seasonal animals which endure food shortages in winter. Evidence
      from several studies suggests that regulation of type 2 and type 3 deiodinase
      enzymes in tanycytes of the third ventricle are gatekeepers of thyroid hormone
      levels in the hypothalamus. This paper reviews some of the evidence for the role
      of deiodinase enzymes and the actions of thyroid hormone in the hypothalamus in
      the regulation of energy balance.

PMID- 20054166
TI  - Lifestyle factors associated with BMI in a Spanish graduate population: the SUN
      Study.
AB  - OBJECTIVE: To study the association between BMI and lifestyle factors such as
      alcohol consumption, smoking habits, education level and marital status in a
      Spanish graduate population. METHOD: Cross-sectional analysis of 8,706
      participants (3,643 men and 5,063 women) from the Seguimiento Universidad de
      Navarra (SUN) Study, an ongoing dynamic cohort study in Spain. Data on body
      weight, height and sociodemographic characteristics, and lifestyle habits were
      collected with self-administered validated questionnaires. RESULTS: Among older
      participants (above sex-specific median age), educational level was a factor
      independently associated with BMI. University graduates with a lower educational
      level (3-year college degree or 5-year university degree) had a significantly
      higher BMI than those with doctorate which requires, at least, 8 years of
      university studies in Spain. Mean BMI was significantly higher among past smokers
      than among never smokers. Alcohol consumption, marital and smoking status were
      associated with BMI only among men. CONCLUSION: In a study whose members were all
      university graduates, several factors were independently associated with a higher
      BMI, such as less years of higher education, past smoking, marital status and
      higher alcohol consumption.

PMID- 20054167
TI  - Relations of mood with body mass index changes in severely obese women enrolled
      in a supported physical activity treatment.
AB  - BACKGROUND/AIMS: It has been suggested that physical activity may affect weight
      reduction outcomes through associated improvements in mood. Relations of physical
      activity, mood, and weight change are not well understood in persons classified
      as severely obese (BMI > or = 40 kg/m(2)), however. This research tested these
      relationships in women with severe obesity. METHODS: 57 women with a mean BMI of
      43.8 kg/m(2) were enrolled in a cognitive-behavioral exercise support treatment
      with group-based nutrition information. Measurement of depression, tension,
      overall mood, and BMI was taken at baseline and month 6, and exercise session
      attendance was recorded. RESULTS: The treatment was associated with significant
      improvements in depression, tension and total mood disturbance scores as well as
      in BMI over 6 months. Changes in mood scores that were more positive were
      correlated with a greater reduction in BMI. Mean attendance in the prescribed 3
      session/week exercise regimen was 46.0%, and attendance was significantly
      correlated with changes in tension and total mood disturbance scores, and
      approached significance with changes in depression scores. CONCLUSION: Findings
      suggested significant relations of mood and weight change as well as of physical
      activity and mood in severely obese women associated with a treatment of moderate
      physical activity. With extensions of this research, weight loss theory and
      treatment may benefit.

PMID- 20054168
TI  - Ingenuity pathway analysis of clozapine-induced obesity.
AB  - BACKGROUND: Lipid accretion is one of the major side effects of clozapine
      pharmacotherapy of schizophrenia that made clozapine into an interesting obesity
      drug model. METHOD: Ingenuity Pathway Analysis (IPA) engine was used for core
      analysis and building the networks of weight regulation. RESULTS: The examination
      of molecules that were selected into 'clozapine neighborhood' identified them as
      multifunctional signals that appear to orchestrate vascular and tissue functions
      plausibly implicated in adiposity side effect. CONCLUSIONS: It is hypothesized
      that clozapine unmasks the functional and morphological phenotype of
      microvascular deficit that facilitates shunting nutrients from utilization toward
      storage.

PMID- 20054169
TI  - Psychosis following anti-obesity treatment with rimonabant.
AB  - BACKGROUND: In this report, we present the case of a patient with a relapse of
      schizophrenia following an episode of depression and increased anxiety after
      antiobesity treatment with rimonabant, a cannabinoid type 1 receptor antagonist.
      CASE REPORT: After 4 weeks of treatment the patient developed psychiatric
      symptoms, i.e. depressed mood and elevated anxiety. Four months after the
      discontinuation of rimonabant, the patient presented with psychotic symptoms
      fulfilling ICD-10 criteria of paranoid schizophrenia. Antipsychotic treatment
      with quetiapine was initialized. A stable recovery took further 4 weeks in which
      combined treatment with quetiapine and ziprasidone was given. CONCLUSION: The
      course of the illness suggests that the continuous affective symptoms, which were
      most likely a side effect of rimonabant, may have triggered the psychosis
      analogous to the stress-diathesis model of schizophrenia. As a consequence,
      rimonabant may not be the first choice in obese patients with a history of
      schizophrenia due to a potentially increased risk of a relapse via an indirect
      mechanism.

PMID- 20054170
TI  - Management of obesity in adults: European clinical practice guidelines.
AB  - The development of consensus guidelines for obesity is complex. It involves
      recommending both treatment interventions and interventions related to screening
      and prevention. With so many publications and claims, and with the awareness that
      success for the individual is short-lived, many find it difficult to know what
      action is appropriate in the management of obesity. Furthermore, the significant
      variation in existing service provision both within countries as well as across
      the regions of Europe makes a standardised approach, even if evidence-based,
      difficult to implement. In formulating these guidelines, we have attempted to use
      an evidence-based approach while allowing flexibility for the practicing
      clinician in domains where evidence is currently lacking and ensuring that in
      treatment there is recognition of clinical judgment and of regional diversity as
      well as the necessity of an agreed approach by the individual and family. We
      conclude that i) physicians have a responsibility to recognise obesity as a
      disease and help obese patients with appropriate prevention and treatment, ii)
      treatment should be based on good clinical care and evidence-based interventions
      and iii) obesity treatment should focus on realistic goals and lifelong
      management.

PMID- 20054171
TI  - GOAT: a stomach enzyme that whets our appetite.

PMID- 20054172
TI  - Pathogenesis, risk assessment and prevention of type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a complex, polygenic disease with a heterogeneous
      pathophysiology, mainly characterised by obesity-associated insulin resistance
      and a progressive failure of pancreatic beta-cells. Predominant risk factors for
      its development are abdominal obesity and age; other factors that augment the
      individual disease risk independent of obesity are the nutritional pattern (low
      consumption of fibres, high consumption of red meat, saturated and trans fat),
      lifestyle (smoking, low physical activity), and biomarkers such as blood
      pressure, HbA1c, serum adiponectin and inflammatory cytokines. These variables
      can provide the basis for a precise risk assessment and a personalised
      prevention. Genotyping for the presently known gene variants conferring an
      increased disease risk adds relatively little to the information provided by the
      phenotypic risk factors and biomarkers. However, genetic information is necessary
      for a personalised risk assessment and intervention that begins before phenotypic
      risk factors are detectable. The incidence of type 2 diabetes can significantly
      be lowered by reduction of the intraabdominal fat mass (by nutritional
      intervention and exercise), and by pharmacological control of post-prandial blood
      glucose excursions. Because of the high portion of non-responders to a preventive
      intervention, current efforts aim at the identification of phenotypic and genetic
      variables predicting the success of the intervention.

PMID- 20054173
TI  - Genotype-phenotype associations in obesity dependent on definition of the obesity
      phenotype.
AB  - OBJECTIVE: In previous studies of associations of variants in the genes UCP2,
      UCP3, PPARG2, CART, GRL, MC4R, MKKS, SHP, GHRL, and MCHR1 with obesity, we have
      used a case-control approach with cases defined by a threshold for BMI. In the
      present study, we assess the association of seven abdominal, peripheral, and
      overall obesity phenotypes, which were analyzed quantitatively, and thirteen
      candidate gene polymorphisms in these ten genes in the same cohort. METHODS:
      Obese Caucasian men (n = 234, BMI >or= 31.0 kg/m(2)) and a randomly sampled non
      obese group (n = 323), originally identified at the draft board examinations,
      were re-examined at median ages of 47.0 or 49.0 years by anthropometry and DEXA
      scanning. Obesity phenotypes included BMI, fat body mass index, waist
      circumference, waist for given BMI, intra-abdominal adipose tissue, hip
      circumference and lower body fat mass (%). Using logistic regression models, we
      estimated the odds for defined genotypes (dominant or recessive genetic
      transmission) in relation to z-scores of the phenotypes. RESULTS: The minor
      (rare) allele for SHP 512G>C (rs6659176) was associated with increased hip
      circumference. The minor allele for UCP2 Ins45bp was associated with increased
      BMI, increased abdominal obesity, and increased hip circumference. The minor
      allele for UCP2 -866G>A (rs6593669) was associated with borderline increased fat
      body mass index. The minor allele for MCHR1 100213G>A (rs133072) was associated
      with reduced abdominal obesity. None of the other genotype-phenotype combinations
      showed appreciable associations. CONCLUSION: If replicated in independent studies
      with focus on the specific phenotypes, our explorative studies suggest
      significant associations between some candidate gene polymorphisms and distinct
      obesity phenotypes, predicting beneficial and detrimental effects, depending on
      compartments for body fat accumulation.

PMID- 20054174
TI  - Economic costs of abdominal obesity.
AB  - BACKGROUND: To examine the relationship between waist circumference and future
      health care costs across a broad range of waist circumference values based on
      individual level data. METHOD: A prospective cohort of 31,840 subjects aged 50-64
      years at baseline had health status, lifestyle and socio-economic aspects
      assessed at entry. Individual data on health care consumption and associated
      costs were extracted from registers for the subsequent 7 years. Participants were
      stratified by presence of chronic disease at entry. RESULTS: Increased waist
      circumference at baseline was associated with higher future health care costs.
      For increased and substantially increased waist circumference health care costs
      rise at a rate of 1.25% in women and 2.08% in men, per added centimetre above
      normal waistline. Thus, as an example, a woman with a waistline of 95 cm and
      without co-morbidities can be expected to incur an added future cost of
      approximately USD 397.- per annum compared to a woman in the normal waist
      circumference group, corresponding to 22% higher health care costs. CONCLUSIONS:
      Future health care costs are higher for persons who have an increased waist
      circumference, which suggests that there may be a potential for significant
      resource savings through prevention of abdominal obesity.

PMID- 20054175
TI  - A heterozygous mutation in the third transmembrane domain causes a dominant
      negative effect on signalling capability of the MC4R.
AB  - BACKGROUND: Heterozygous MC4R mutation is the most frequent cause of monogenic
      obesity. For most MC4R mutations a gene dosage effect seems to be the underlying
      mechanism. However, a dominant negative effect of a heterozygous MC4R mutation
      was recently identified, pointing to an additional mechanism of MC4R
      inactivation. METHODS: The complete loss-of-function mutation (Ser136Phe),
      identified in a cohort of obese Austrian patients, was characterized for cell
      surface expression, signal transduction and ligand binding properties. Co
      transfection studies tested for a dominant negative effect. Dimerization was
      investigated by a sandwich ELISA and by fluorescence resonance energy transfer
      (FRET) approach. Potential intramolecular interactions of Ser136 were studied by
      homologous receptor modelling based on the crystal structure of the beta2
      adrenergic receptor. RESULTS: The Ser136Phe mutation showed a dominant negative
      effect. The sandwich ELISA and FRET approach demonstrated dimerization of mutant
      and wild type receptor. Receptor modelling revealed an essential function of
      Ser136 at transmembrane helix 3 (TMH3) for establishing H-bonds between TMH2,
      TMH3, and TMH7. The mutation Ser136Phe most likely disrupts this network and
      leads to an incompetent helix-helix arrangement in the mutated receptor.
      CONCLUSION: Identification of dominant negative MC4R mutations is important to
      fully understand receptor function and to determine receptor regions that are
      involved in MC4R dimer activation.

PMID- 20054176
TI  - Welcome, section editors!

PMID- 20054178
TI  - Fat tissue and long life.
AB  - Studies over the last several years have revealed important roles of the body fat
      content, caloric intake and nutrition, insulin/IGF-1 signaling systems, and
      pathways involved in oxidative stress and control of protein acetylation on life
      span. Although the discovery of longevity genes supports the concept that life
      span is genetically determined, adipose tissue seems to be a pivotal organ in the
      aging process and in the determination of life span. Leanness and caloric
      restriction have been shown to increase longevity in organisms ranging from yeast
      to mammals. Increased longevity in mice with a fat-specific disruption of the
      insulin receptor gene (FIRKO) suggests that reduced adiposity, even in the
      presence of normal or increased food intake, leads to an extended life span.
      Reduced fat mass has an impact on longevity in a number of other model organisms.
      In Drosophila, a specific reduction in the fat body through overexpression of
      forkhead type transcription factor (dFOXO) extends life span. Sirtuin 1 (SIRT1),
      the mammalian ortholog of the life-extending yeast gene silent information
      regulator 2 (SIR2), was proposed to be involved in the molecular mechanisms
      linking life span to adipose tissue. Moreover, in the control of human aging and
      longevity, one of the striking physiological characteristics identified in
      centenarians is their greatly increased insulin sensitivity even compared with
      younger individuals. On the other hand, overweight and obesity seem to be
      associated with decreased life span in humans. In addition, it was recently shown
      that modifiable risk factors during the later years of life, including smoking,
      obesity, and hypertension, are associated not only with lower life expectancy,
      but also with poor health and function during older age. There is growing
      evidence that the effect of reduced adipose tissue mass on life span could be due
      to the prevention of obesity-related metabolic disorders including type 2
      diabetes and atherosclerosis.

PMID- 20054179
TI  - Human SGBS cells - a unique tool for studies of human fat cell biology.
AB  - The human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell strain provides
      a unique and useful tool for studies of human adipocyte biology. The cells
      originate from an adipose tissue specimen of a patient with SGBS. They are
      neither transformed nor immortalized, and provide an almost unlimited source due
      to their ability to proliferate for up to 50 generations with retained capacity
      for adipogenic differentiation. So far, the cells have been used for a number of
      studies on adipose differentiation, adipocyte glucose uptake, lipolysis,
      apoptosis, regulation of expression of adipokines, and protein translocation. The
      cells are efficiently differentiated in the presence of PPARgammaagonists and in
      the absence of serum and albumin. SGBS adipocytes respond to insulin stimulation
      by increasing glucose uptake several-fold (EC50 approximately 100 pmol/l), and by
      very effectively inhibiting (IC50 approximately 10 pmol/l) catecholamine
      stimulated lipolysis.

PMID- 20054180
TI  - Indices of obesity and cardiovascular risk factors in British women.
AB  - BACKGROUND: Obesity increases cardiovascular risk through effects on blood
      pressure, lipoproteins, coagulation factors and inflammatory cytokines, but in
      women variation in fat distribution complicates these relationships. Central
      (male-type or visceral) obesity confers greater risk than the more generalised
      (female) type. This is recognised by the metabolic syndrome which employs waist
      circumference rather than body mass index (BMI). We examined the relationships of
      several indices of fat distribution with cardiovascular risk factors in a large
      cohort of UK women. MATERIAL AND METHODS: 13,389 female department store
      employees aged 30-65 years not receiving exogenous hormones completed a health
      questionnaire. Their blood pressure, weight, height, waist and hip circumference,
      serum cholesterol low density lipoprotein cholesterol (LDL-C), high density
      lipoprotein cholesterol (HDL-C), triglycerides, C-reactive protein (CRP) and
      plasma fibrinogen were measured. RESULTS: There was a progressive rise in blood
      pressure, total cholesterol, LDL-C, triglycerides, fibrinogen and CRP with age.
      After adjustment for these age effects, BMI was most closely related to blood
      pressure, whereas the waist to height ratio (WHTR) correlated more closely with
      the other risk factors than BMI, waist circumference or waist to hip ratio
      (WHPR). CONCLUSIONS: Inclusion of height in the definition of metabolic syndrome
      will produce a clearer association between waist circumference and cardiovascular
      risk factors. Hypertension may be linked to the metabolic syndrome by its
      association with general obesity rather than specifically by central obesity.

PMID- 20054181
TI  - Clustering of obesity and dental health with lifestyle factors among Turkish and
      Finnish pre-adolescents.
AB  - BACKGROUND: This study aims to assess any clustering between obesity, number of
      decayed, missing, and filled teeth (DMFT), television (TV) viewing, and lifestyle
      factors among pre-adolescents living in 2 countries with different developmental
      status and oral health care systems - Turkey and Finland. PATIENTS AND METHODS: A
      cross-sectional study of Finnish (n = 338) and Turkish (n = 611) preadolescents,
      10-12 years old, was undertaken with preadolescent oral health data and health
      behavior questionnaires for pre-adolescents and their mothers. The parameters
      examined were DMFT, body mass index (BMI), leisure time activities (TV viewing),
      and lifestyle factors (family dinners and dietary habits) of pre-adolescents.
      Data analysis included factor analysis, Student's t-test, and Chi-square tests by
      cross tabulation. RESULTS: Turkish pre-adolescents were more obese and had poorer
      dental health than their Finnish counterparts (p < 0.05). Turkish and Finnish pre
      adolescents drinking fizzy drinks more than 3 times a week were more likely to
      watch TV for >or= 2 h/school day (odds ratio (OR) = 1.51, 95% confidence interval
      (CI) 1.00-2.28) than those consuming them once a week or less (OR = 3.06, 95% CI
      1.39-6.75; p < 0.05). Factor analysis revealed that DMFT and obesity shared the
      same cluster among Turkish and Finnish pre-adolescents. CONCLUSION: Both medical
      and dental examination of any pediatric patient should include BMI, leisure time
      activities, and dietary habits as well as socio-economic status.

PMID- 20054182
TI  - The 1D1 of burning calories.

PMID- 20054183
TI  - A health assessment tool for multiple risk factors for obesity: psychometric
      testing and age differences in UK adults.
AB  - BACKGROUND: Although many individual health behaviours (e.g. diet/activity) have
      been implicated in the current rise in obesity levels, their confounding or
      cumulative effects have yet to be established. This study psychometrically tested
      a previously piloted comprehensive measure of obesity risk factors, designed to
      assess their relative importance at individual and population levels. MATERIAL
      AND METHODS: A user-friendly, self-report questionnaire, completed by 359 adult
      volunteers (71% female, age range 18-81 years), was subjected to exploratory
      factor analysis and related to body mass index (BMI) and age. RESULTS: The final
      solution had 74 items and showed a clear factor structure, with 5 dietary and 5
      activity factors, plus 8 unrelated factors covering dieting behaviour, alcohol
      consumption, sleep, and varied developmental influences. Younger respondents
      generally reported unhealthier behaviours. Once age was controlled for, less
      healthy eating, more emotional eating, higher amounts eaten, less physical
      activity, more use of mechanised transport, and more/less successful dieting
      behaviour were all strongly related to higher BMI, with lesser associations for
      more TV watching and less parental encouragement to be active. CONCLUSION: This
      easy-touse self-report measure of multiple risk factors showed good psychometric
      properties and has merit in determining the contribution of varied factors in the
      tendency to overweight and obesity. The finding that younger adults generally
      reported less healthy dietary and activity behaviour indicates a pressing need
      for early intervention.

PMID- 20054184
TI  - Overweight and cardiovascular risk factors in 4- to 18-year-olds.
AB  - BACKGROUND: The objective of this study was to investigate the relationships
      between overweight and high waist circumference and cardiovascular risk factors
      in children. MATERIAL AND METHODS: We carried out a secondary analysis of data
      from 1,944 participants of the 'National Diet and Nutrition Survey: young people
      aged 4-18 years'. Blood pressure and blood lipid levels were compared in
      overweight versus non-overweight and high versus low waist circumference groups.
      Overweight was defined using international cut-offs for body mass index. High
      waist circumference was defined as >or= 91st percentile of UK waist circumference
      charts. Analyses were done separately by sex and age group (4-10 and 11-18 years
      for overweight, and 11-17 years for waist circumference). RESULTS: Overweight and
      high waist circumference were associated with increased systolic blood pressure,
      mean arterial pressure, low-density lipoprotein cholesterol (LDLC) and
      triacylglycerol, and decreased high-density lipoprotein cholesterol (HDLC). Those
      who were both overweight and had a high waist circumference had the highest blood
      pressure, plasma LDLC and triacylglycerol, and the lowest plasma HDLC.
      CONCLUSION: Overweight and high waist circumference were associated with
      increased blood pressure and a less favourable lipid profile. Children who were
      both overweight and had a high waist circumference had the most unfavourable
      cardiovascular risk profile. Both measurements may be useful in identifying
      children with increased health risks.

PMID- 20054185
TI  - Measurement of waist circumference at four different sites in children,
      adolescents, and young adults: concordance and correlation with nutritional
      status as well as cardiometabolic risk factors.
AB  - BACKGROUND: This study investigates the concordance of four waist circumference
      (WC) measurement sites, and examines their relationships with nutritional status
      and cardiometabolic risk. SUBJECTS AND METHODS: In 91 females / 89 males (6.1
      19.9 years; 12.2% overweight), WC was assessed beneath the lowest rib (WCR), 4 cm
      above the umbilicus (WC4), above the iliac crest (WCC), and midway between
      WCR/WCC (WCM). 'Overwaist' was defined as a WC > 90th age-/sex-specific
      percentile. Pubertal stage was assessed according to Tanner. Body composition
      (air-displacement plethysmography), blood pressure, lipid profile,
      glucose/insulin levels, and HOMA-IR (homeostasis model assessment of insulin
      resistance) were measured. RESULTS: Medians of WCs (cm) for females/males were
      WCR (64.4/69.5) < WC4 (64.6/70.2) < WCM (67.1/71.2) < WCC (71.5/ 74.2). Although
      closely related to each other (all r > 0.93; p < 0.001), paired comparisons
      revealed differences between WCs in their magnitudes which was stronger for
      females than males. Prevalence of 'overwaist' differed according to measurement
      site in females/males: WCR (13.2/15.7%) < WC4 (14.3/ 19.1%) < WCM (18.7/22.5%) <
      WCC (37.4/30.3%). After adjusting for age and pubertal status, WCs were closely
      related to body mass index (BMI) (all r > 0.86; p < 0.001), percent fat mass
      (%FM; all r > 0.61; p < 0.001), and comparably associated with cardiometabolic
      risk factors. However, stronger correlations were found for i) WCR vs. WC4 with
      BMI in males (r = 0.93 vs. 0.91; p < 0.05), ii) WCC vs. WC4 with %FM in females
      (r = 0.67 vs. 0.61; p < 0.05), iii) WCC vs. WCR with triglycerides in females (r
      = 0.29 vs. r = 0.22; p < 0.05), and iv) WCC (r = 0.36) vs. other WCs (r = 0.30
      0.32) with low-density lipoprotein cholesterol (LDL-C) in males (p < 0.05).
      CONCLUSION: WCs measured at different sites were closely correlated with BMI and
      %FM as well as comparably associated with cardiometabolic risk factors. However,
      different WCs had different magnitudes, which was more obvious in females and led
      to discordant results with respect to 'overwaist' and risk assessment.

PMID- 20054186
TI  - Prevalence of obesity and abdominal obesity in Swedish primary care and
      occupational health clinics.
AB  - BACKGROUND: The objective of this study was to describe the prevalence of obesity
      and abdominal obesity in the Swedish primary and occupational health care
      setting. PATIENTS AND METHODS: Weight, height, and waist circumference (WC) were
      measured in 1,583 consecutive patients, aged between 18-65 years (46.4 +/- 12.7
      years), in 39 primary care and occupational health practices in Sweden, in 2006.
      The National Cholesterol Education Program (NCEP) WC reference values were used
      to define abdominal obesity (102 and 88 cm for men and women, respectively).
      RESULTS: The distribution across obesity categories differed significantly
      between men and women with close to 70 and 55% of men and women, respectively,
      having a body mass index (BMI) >or= 25. More men than women were overweight (BMI
      25-29.9; 45.1 vs. 31.1%) and obese (BMI 30-34.9; 19.8 vs. 12.9%), but less men
      than women were morbidly obese (4.0 vs. 8.9%; BMI >or= 35). Increasing prevalence
      with age was seen until age 60 for both overweight and obesity. More women than
      men were abdominally obese (42.5 vs. 32.7%; p < 0.001). Only 48 and 64% of the
      abdominally obese women and men, respectively, had a BMI >or= 30. CONCLUSION:
      Compared to national Swedish data, the prevalence of overweight and obesity was
      higher in primary and occupational health care settings. Both morbid obesity and
      abdominal obesity were highly prevalent and more common in women, implying that
      awareness of sex differences may be important or that recommended cut-offs are
      not comparable across sex. Furthermore, a large fraction of the abdominally obese
      had a BMI < 30. Both BMI and WC may therefore be important to determine routinely
      and incorporate into treatment guidelines, in order not to miss patients at risk
      of obesity-related morbidity.

PMID- 20054187
TI  - Circulating markers of inflammation and their link to indices of adiposity.
AB  - BACKGROUND: Adipose tissue produces a number of inflammatory mediators.
      Circulating concentrations of these inflammatory markers are increasingly used as
      markers of local or systemic inflammation. This study compares results for 3
      inflammatory adipokines measured using 2 techniques, (multiplex and ELISA), and
      determines the relationships with C-reactive protein (CRP), obesity, and the
      impact of moderate weight loss. SUBJECTS AND METHODS: Fasting blood samples were
      collected at baseline and after a 24-week weight loss intervention. Interleukin 6
      (IL-6), tumour necrosis factor alpha(TNF-alpha), and monocyte chemoattractant
      protein 1 (MCP-1) were measured using a standard ELISA technique or a new
      multiplex technique. A total of 54 women with complete data were included in this
      analysis. RESULTS: Multiplex showed poor correlation with ELISA results, and were
      not significantly correlated with CRP. Using ELISA data, IL-6 and CRP were
      significantly correlated with body mass index (BMI) (r = 0.42 and r = 0.55), but
      MCP-1 and TNF-alpha were not (r = - 0.07 and r = 0.06). Changes in MCP-1, TNF
      alpha, and IL-6 were not significantly different between control and weight loss
      groups. CRP was significantly reduced in weight loss vs. control group (p <
      0.05), and change in CRP correlated with change in BMI (r = 0.31). CONCLUSION:
      Circulating IL-6 and CRP, but not MCP-1 and TNF-alpha, are significantly
      associated with indices of adiposity in obese women. This study suggests that
      circulating IL-6 and CRP, but not MCP-1 and TNF-alpha, are useful markers of
      obesity-related inflammation.

PMID- 20054188
TI  - Influence of partial sleep deprivation on energy balance and insulin sensitivity
      in healthy women.
AB  - BACKGROUND: Voluntary sleep restriction is a lifestyle feature of modern
      societies that may contribute to obesity and diabetes. The aim of the study was
      to investigate the impact of partial sleep deprivation on the regulation of
      energy balance and insulin sensitivity. SUBJECTS AND METHODS: In a controlled
      intervention, 14 healthy women (age 23-38 years, BMI 20.0-36.6 kg/m(2)) were
      investigated after 2 nights of >8 h sleep/night (T0), after 4 nights of
      consecutively increasing sleep curtailment (7 h sleep/night, 6 h sleep/night, 6 h
      sleep/night and 4 h sleep/night; T1) and after 2 nights of sleep recovery (>8 h
      sleep/night; T2). Resting and total energy expenditure (REE, TEE), glucose
      induced thermogenesis (GIT), physical activity, energy intake, glucose tolerance
      and endocrine parameters were assessed. RESULTS: After a decrease in sleep du
      ration, energy intake (+20%), body weight (+0.4 kg), leptin/fat mass (+29%), free
      triiodothyronine (+19%), free thyroxine (+10%) and GIT (+34%) significantly
      increased (all p < 0.05). Mean REE, physical activity, TEE, oral glucose
      tolerance, and ghrelin levels remained unchanged at T1. The effect of sleep loss
      on GIT, fT3 and fT4 levels was inversely related to fat mass. CONCLUSION: Short
      term sleep deprivation increased energy intake and led to a net weight gain in
      women. The effect of sleep restriction on energy expenditure needs to be
      specifically addressed in future studies using reference methods for total energy
      expenditure.

PMID- 20054190
TI  - Should we really treat every obese individual?

PMID- 20054189
TI  - Influence of calcium and vitamin D supplementation on weight and fat loss in
      obese women.
AB  - BACKGROUND: Dairy products not only reduce the risk of hypertension and
      cardiovascular diseases but may play a role in the treatment of obesity. As there
      is some evidence that calcium (Ca) and vitamin D may play a role in effective
      weight management, we decided to evaluate the influence of Ca and vitamin D
      supplementation on weight and fat loss in obese women. MATERIAL AND METHODS:
      Forty obese women were enrolled in this study. Subjects were divided into 2
      groups comparable with body mass index (BMI) and age. Group 1 was provided with
      calcium carbonate and 1-(OH)-vitamin D supplementation. Group 2 was provided with
      only a diet. Subjects participated in a 3-month weight reduction therapy
      (balanced diet, modification of life style, and regular physical exercise). Blood
      samples (serum concentration of Ca, phosphorus (P), parathormone (PTH), 25-(OH)
      D3) and clinical characteristics (weight, height, BMI, body composition) were
      taken at baseline and after the 3-month program. RESULTS: No significant
      differences of body weight, body fat content, serum parathormone, 25-(OH)-D3
      concentration, and plasma total Ca and P concentration were observed between
      analyzed groups both before and after the treatment. Additionally, we did not
      observe any significant influence of Ca and vitamin D supplementation on weight
      and fat loss. CONCLUSION: Ca plus vitamin D supplementation during a 3-month low
      caloric diet has no additional effect on weight and fat loss in obese women.

PMID- 20054191
TI  - High-fat, carbohydrate-free diet markedly aggravates obesity but prevents beta
      cell loss and diabetes in the obese, diabetes-susceptible db/db strain.
AB  - OBJECTIVE: We have previously reported that a high-fat, carbohydrate-free diet
      prevents diabetes and beta-cell destruction in the New Zealand Obese (NZO) mouse
      strain. Here we investigated the effect of diets with and without carbohydrates
      on obesity and development of beta-cell failure in a second mouse model of type 2
      diabetes, the db/db mouse. RESULTS: When kept on a carbohydrate-containing
      standard (SD; with (w/w) 5.1, 58.3, and 17.6% fat, carbohydrates and protein,
      respectively) or high-fat diet (HFD; 14.6, 46.7 and 17.1%), db/db mice developed
      severe diabetes (blood glucose >20 mmol/l, weight loss, polydipsia and polyurea)
      associated with a selective loss of pancreatic beta-cells, reduced GLUT2
      expression in the remaining beta-cells, and reduced plasma insulin levels. In
      contrast, db/db mice kept on a high-fat, carbohydrate-free diet (CFD; with 30.2
      and 26.4% (w/w) fat or protein) did not develop diabetes and exhibited near
      normal, hyperplastic islets in spite of a morbid obesity (fat content >60%)
      associated with hyperinsulinaemia. CONCLUSION: These data indicate that in
      genetically different mouse models of obesity-associated diabetes, obesity and
      dietary fat are not sufficient, and dietary carbohydrates are required, for beta
      cell destruction.

PMID- 20054192
TI  - Employing RMR technology in a 90-day weight control program.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of a weight
      management program using indirect calorimetry to set energy goals. METHODS: 54
      overweight, active duty adult employees of the US Air Force (age 18-46 years, BMI
      25.2-35.6 kg/m(2)) participated in this quasi-experimental control design study.
      All participants were enrolled in a four-session US Air Force 'Sensible Weigh'
      group weight control program. Treatment participants received a personalized
      nutrition energy goal message developed using measured resting metabolic rate
      (RMR) from a hand-held indirect calorimeter (MedGem). Usual care participants
      received a nutritional message using a standard care equation (25 kcal/day x body
      weight) to set energy intake goals. RESULTS: Treatment participants lost
      significantly more weight than usual care participants (p < or = 0.05).
      Difference in weight loss between the treatment and usual care group were -4.3 kg
      +/- 3.3 vs. -1.8 kg +/- 3.2, respectively. There were no significant differences
      in reported food intake or energy expenditure between groups. CONCLUSION: The use
      of indirect calorimetry to assess RMR and set energy intake goals positively
      influences weight loss success in overweight Air Force personnel.

PMID- 20054193
TI  - Evaluating the association of FAAH common gene variation with childhood, adult
      severe obesity and type 2 diabetes in the French population.
AB  - OBJECTIVE: The endocannabinoid pathway is involved in eating behavior and body
      weight regulation in both animals and humans. The association of a missense
      polymorphism (Pro129Thr) in FAAH gene with overweight/obesity has been recently
      questioned. SUBJECTS AND METHODS: To evaluate the contribution of the FAAH gene
      variation in polygenic obesity and type 2 diabetes mellitus (T2DM) in the French
      population, we investigated the entire FAAH locus. We selected and genotyped ten
      tagged single nucleotide polymorphisms (SNPs) in 635 obese children, 896 morbidly
      obese adults, 2,238 T2DM subjects and 1,340 control subjects, all of French
      European origin. Case control association tests were performed using logistic
      regression models. RESULTS: Nominal evidences of association were observed for
      rs6429600, rs324419, rs324418, rs2295633, rs7520850 and risk for class III adult
      obesity (0,001 < p < 0.04). The rs324420 (Pro129Thr) was nominally associated
      with class III adult obesity (ORadditive = 0.79 (95% CI 0.67-0.93), p = 0.005;
      ORdominant = 0.76 (95% CI 0.63-0.92), p = 0.005), Pro129 being the obesity risk
      allele. These associations did not remain significant after Bonferroni correction
      for multiple testing. There was no significant association between FAAH SNPs and
      risk for childhood obesity or T2DM. CONCLUSION: Our results in 5,109 subjects
      suggest that FAAH Pro129Thr polymorphism may modestly contribute to class III
      adult obesity in the French population. Further validation is needed to precise
      the role of this gene variant in obesity susceptibility background.

PMID- 20054194
TI  - Mid-thigh subcutaneous adipose tissue and glucose tolerance in the Quebec family
      study.
AB  - OBJECTIVE: To clarify the relationship between the amount of mid-thigh
      subcutaneous adipose tissue (SCAT) and glucose tolerance in men and women.
      METHODS: Midthigh and abdominal computed tomography (CT) scans were obtained from
      63 men and 110 women from the Quebec Family Study. Areas and attenuations of
      adipose tissue compartments and skeletal muscle measured from CT scans were
      related to glycemia and insulinemia values from an oral glucose tolerance test
      (OGTT). RESULTS: Adjusted for age and fat mass or age and percent fat, negative
      relationships (all p < 0.05) between the surface area of mid-thigh SCAT and OGTT
      data (glucose and insulin area under the curve, glycemia and insulin at 120 min)
      were seen in men (r range -0.22 to -0.37) and women (r range -0.20 to -0.30).
      Similar but weaker tendencies were observed when correcting for visceral
      adiposity. Correlations of OGTT variables with ratios of midthigh SCAT to
      abdominal visceral adipose tissue and to fat mass revealed significant negative
      relationships in both genders. Tertile analyses showed better glucose handling in
      subjects with a higher content of mid-thigh SCAT. CONCLUSION: These data suggest
      that the preferential deposition of adipose tissue as mid-thigh SCAT is a
      strategy to prevent glucose intolerance.

PMID- 20054195
TI  - Accuracy of bioelectrical impedance consumer devices for measurement of body
      composition in comparison to whole body magnetic resonance imaging and dual X-ray
      absorptiometry.
AB  - OBJECTIVE: To compare body composition determined by bioelectrical impedance
      (BIA) consumer devices against criterion estimates determined by whole body
      magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DXA) in
      healthy normal weight, overweight and obese adults. METHODS: In 106 adults (54
      females, 52 males, age 54.2 +/- 16.1 years, BMI 25.8 +/- 4.4 kg/m(2)) fat mass
      (FM), skeletal muscle mass (SM), total body bone-free lean mass (TBBLM), and
      level of visceral fat mass (VF) were estimated by 3 single-frequency bipedal
      (foot-to-foot) and one tretrapolar BIA device, and compared to body composition
      measured by MRI and DXA. Bland-Altman and simple linear regression analyses were
      used to determine agreement between methods. RESULTS: %FMDXA, SMMRI or TBBLMDXA
      showed good relative and absolute agreement with two bipolar and one tetrapolar
      instrument (r(2) = 0.92-0.96; all p < 0.001; mean bias <1.5 %FM and <1 kg SM or
      TBBLM) and less relative and absolute agreement for another bipolar device (r(2)
      = 0.82 and 0.84, mean bias approximately 3 %FM and approximately 3 kg SM). The
      95% limits of agreement (bias +/- 2 SD) were narrowest for the tetrapolar device
      (-6.59 to 4.61 %FM and -4.62 to 4.74 kg SM) and widest for bipolar instruments
      (up to -14.54 to 8.58 %FM and -9.52 to 3.92 kg SM). Systematic biases for %FM
      were found for all bipedal devices, but not for the tetrapolar instrument.
      CONCLUSION: Because of the lower agreement between foot-to-foot BIA and DXA or
      MRI for the assessment of body composition in individuals, tetrapolar electrode
      arrangement should be preferred for individual or public use. Bipolar devices
      provide accurate results for field studies with group estimation.

PMID- 20054196
TI  - Assessment of representativity of a study population - experience of the Kiel
      Obesity Prevention Study (KOPS).
AB  - OBJECTIVE: Exemplified by data of the Kiel Obesity Prevention Study (KOPS),
      different methods to control for response bias and to assess representativity
      were compared. METHODS: 4,997 cross-sectional data of 5- to 7-year-old German
      children (main cohort) were investigated between 1996 and 2001 within school
      entry examination. A subgroup responded to a questionnaire to socio-demographic
      and lifestyle factors (responders, n = 2,631). Representativity of the main
      cohort was tested in comparison to the total population. To control for response
      bias within the responders a non-response analysis as well as an analysis of
      missing values were performed. RESULTS: The comparison with the total population
      showed a higher prevalence of obese boys and girls from families of low socio
      economic status (SES) within the main cohort. The responders were less frequently
      obese and overweight and more rarely belonged to low SES families when compared
      with non-responders. Analysis of missing values did not detect any further
      biases. According to an epidemiological assessment of differences the main cohort
      of KOPS is suggested to be representative for all 5- to 7-year-old children in
      Kiel, whereas the responders can be at best called 'relatively' representative.
      CONCLUSION: The analysis of non-response is the most sensitive method to detect
      group differences, but a comparison with the total population can also be used to
      control for biases. In addition representativity has to be proven not only for
      the main cohort but also for the subgroup of responders with which data analysis
      will be done.

PMID- 20054197
TI  - Fiber intake, not dietary energy density, is associated with subsequent change in
      BMI z-score among sub-groups of children.
AB  - OBJECTIVE: Results from short-term studies demonstrate that energy density
      influences energy intake, but in children and adolescents the long-term effects
      of energy density and obesity development are sparse. We examined the
      longitudinal relationship between dietary energy density, fiber intake, and body
      weight change over 3 years among Danish children. METHODS: Multiple regression
      analyses were performed using anthropometric and dietary data of 398 boys and
      girls (8-10 years) who were enrolled in 1997/1998 and followed up in 2000/2001.
      Validated 24-hour recall interviews were conducted in order to collect dietary
      energy intake. Overweight was defined as 1.05 SD, equivalent to the 85th
      percentile, of age- and sex-specific BMI z-score reference values. RESULTS: An
      inverse association between fiber intake and subsequent excess weight gain was
      observed among the normal weight boys. In overweight boys, there was a direct
      association with excess weight gain. A high energy intake was associated with a
      higher weight gain among overweight than among normal-weight boys. No significant
      association between dietary energy density and subsequent excess weight change
      was seen. The prevalence of overweight increased from 27.1 to 29.9%. Mean Deltaz
      score was +0.1 and +0.4 for boys and girls, respectively. CONCLUSION: Dietary
      energy density was not associated with 3-year weight gain in boys and girls. Only
      energy and fiber intakes were related to weight gain, but in different ways for
      subgroups of normal-weight and overweight boys.

PMID- 20054198
TI  - Three at one swoop!

PMID- 20054199
TI  - Bariatric psychology, psychological aspects of weight loss surgery.
AB  - Obesity is the 'disease of the 21st century' and results in physical and
      psychosocial co-morbidities as well as poor quality of life (QoL). In contrast to
      the nonsurgical treatment of obesity, bariatric surgery is treatment of choice
      for morbid obesity. Since improved QoL and enhanced psychosocial functioning are
      important goals of bariatric surgery, success following bariatric surgery should
      not only include weight loss and improvement or cure of co-morbid conditions, but
      also improvements in eating behavior, psychosocial variables, and QoL.
      Unfortunately, bariatric surgery does not lead to identical results in every
      patient. Patients who fail to adjust their eating behavior and lifestyle after
      bariatric surgery may experience adverse reactions. Compliance and adjustment may
      be attributed largely to psychological factors, implying that the operation on
      its own represents only one element in bariatric surgery. Considering the role of
      psychosocial factors in the outcomes of bariatric surgery and the impact of the
      operation on the psychological and social situation, mental health professionals
      should be a part of the process of evaluation and treatment of bariatric surgery
      patients. In the Netherlands, between 2000 and 2005, bariatric surgery has
      increased tremendously, and most Dutch hospitals have a multidisciplinary
      selection process.

PMID- 20054200
TI  - A systematic review of the effectiveness of group versus individual treatments
      for adult obesity.
AB  - BACKGROUND: Both group and individual modes of delivery are employed for obesity
      treatments. Commercial weight loss groups commonly employ group-based delivery,
      while many clinical based settings employ one-to-one delivery. We systematically
      reviewed randomised controlled trials of treatments for adult obesity to compare
      the effectiveness of group-based to individual-based modes of treatment delivery.
      METHODS: We searched 7 electronic databases and 2 journals and reviewed secondary
      references, based on a priori criteria to systematically review: randomised
      controlled trials of obesity treatments, participants with BMI >or=28 kg/m(2),
      age >or=18 years, comparison groups including at least 1 group-based and 1
      individual-based treatment group, and follow-up >or=1 year. We extracted data and
      conducted meta-analysis of weight change. RESULTS: Eleven comparison groups from
      5 qualifying trials were obtained, representing a total participant pool of 336.
      Significantly greater (p = 0.03) weight change at 12 months was found in group
      based over individualbased treatment, and sub-analyses showed that increased
      effectiveness was associated with the use of financial reward and psychologist
      led interventions. CONCLUSION: Group-based interventions were more effective than
      individual-based interventions among a predominantly female participant pool
      receiving psychologist-led interventions. Future studies to explore differences
      by professional group and interventions among men, which are accompanied by
      economic evaluation, are recommended.

PMID- 20054201
TI  - Obesity and polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in
      women of fertile age. Obesity is encountered in 30-70% of PCOS-affected women,
      and its presence significantly modifies both clinical and laboratory expression
      of the syndrome. Obesity increases the risk of co-morbidities associated with
      PCOS, such as impaired glucose tolerance and type 2 diabetes mellitus,
      hyperlipidemia and arterial hypertension. The etiopathogenesis of obesity in PCOS
      has not yet been exactly clarified. There clearly is a vicious circle of
      abdominal obesity, insulin resistance, and hyperadrogenemia. Differences in
      ghrelin and neuropeptide Y levels between PCOS patients and those with simple
      obesity were also described. Weight loss is the first choice recommendation for
      the treatment of clinical manifestations of PCOS, such as menstrual cycle
      irregularities, infertility or hirsutism. However, the best treatment approach in
      obese PCOS patients remains to be defined. Studies concerning different weight
      loss regimens, antiobesity drugs, bariatric surgery, insulin sensitizers, and
      hormonal therapy are reviewed.

PMID- 20054202
TI  - Compounds used for 'injection lipolysis' destroy adipocytes and other cells found
      in adipose tissue.
AB  - BACKGROUND: A widely applied technique to reduce subcutaneous fat pad size
      involves subcutaneous injection of a phosphatidylcholine preparation ('injection
      lipolysis'). As the mode of action is mostly unknown, we planned to study
      cellular effects of the particular drug used in Germany (Lipostabil(R)). METHODS:
      Human preadipocytes, adipocytes, vascular and skeletal muscle cells as well as
      renal epithelial cells were incubated in the compound, morphological changes were
      described, and cell vitality was measured. RESULTS: A strong cytolytic effect of
      the compound was signified by lipid release and acridine orange staining of dying
      adipocyte nuclei. When the undiluted compound was used, more than 90% of cell
      death occurred after 90 s in preadipocytes, after 6 min in vascular smooth muscle
      cells, skeletal myotubes and renal epithelial cells, and after 15 min in
      adipocytes. Dilution slowed down cytolysis, but still >50% of the cells
      disappeared during 30 min incubation. Neither osmotic effects nor differences in
      medium acidity were responsible for cell death. CONCLUSION: Injection lipolysis
      with phosphatidylcholine as the major injected compound reduces subcutaneous fat
      pad size through cell and tissue destruction. Beside the lack of a clear risk
      benefit analysis, applying this technique represents off-label drug use and
      application of a drug by a contraindicated route.

PMID- 20054203
TI  - Procolipase gene: no association with early-onset obesity or fat intake.
AB  - BACKGROUND: Several lines of evidence in volvement of procolipase (CLPS) or its
      derivative enterostatin in dietary fat absorption, regulation of fat intake, and
      body weight in rodents. We explored the relationship between genetic variation in
      CLPS, early-onset obesity and fat intake in humans. METHODS: We screened the CLPS
      in 93 extremely obese children and adolescents and 96 underweight young adults
      for sequence variations and genotyped single nucleotide polymorphisms (SNPs) in
      extremely obese children and adolescents, healthy normal-and underweight young
      adults and obesity trios. Case-control and family-based association analyses were
      performed. RESULTS: Five sequence variations were identified: two non-synonymous
      SNPs: rs2766597 (Leu8Pro), rs41270082 (Arg109Cys); one SNP in the 5'UTR:
      rs3748050; one intronic SNP: rs3748051; and one infrequent novel non-synonymous
      variant: Arg55His. For rs2766597, rs3748050, and rs3748051 we obtained no
      evidence for an association with obesity in the case-control comparison. For
      rs41270082 there was a trend for association which could not be substantiated in
      the family-based association analysis. Additionally, we found no association in
      subgroup analyses pertaining to the extremely obese children and adolescents in
      the lowest and highest quartile of the percentage of energy consumed as fat.
      CONCLUSIONS: We found no evidence for an association of CLPS SNPs rs2766597,
      rs41270082, rs3748050, and rs3748051 with obesity or percentage of dietary fat
      intake.

PMID- 20054204
TI  - Obesity in print: an analysis of daily newspapers.
AB  - BACKGROUND: Stigmatizing attitudes towards obese people are common in the public.
      Based on findings that portrayals of obesity in entertainment media foster weight
      related stigmatization, the goal of the current study was to analyze media
      coverage of obesity in daily newspapers. METHODS: For the year 2006, all 1,563
      issues of five high-circulation daily newspapers (two national newspapers, one
      tabloid newspaper, and two local newspapers) in Germany were systematically
      searched for obesity-related terms. Out of these issues, 222 articles about human
      overweight were identified and subjected to a quantitative content analysis using
      a reliable coding system. RESULTS: The national and local newspapers examined
      offered more comprehensive and less incorrect information about obesity than the
      tabloid newspaper. Compared with the other types of papers, the information about
      obesity in the local papers was less negative and less catastrophizing. The
      national newspapers presented more attributions of obesity to internal,
      controllable causes than the other newspaper types, and the tabloid newspaper
      used more personalized descriptions of cases with extreme features. CONCLUSION:
      The current coverage of obesity in daily newspapers may contribute to
      stigmatization. Future research should examine readers' reception of newspaper
      information and potential destigmatization through more precise and less
      subjective coverage of obesity.

PMID- 20054205
TI  - Diagnostic crossover from obesity to atypical anorexia nervosa - a case report.
AB  - A 15-year-old, female, formerly obese adolescent was referred to our day care
      clinic due to self-induced massive weight loss and depressive symptoms. Intense
      treatment, additional dialectical behavioral therapy and psychopharmacological
      treatment prevented further weight loss and improved her affective state. Due to
      remaining anorexic symptoms such as body image distortion, outpatient
      psychotherapeutic treatment is continued. This case report indicates the
      importance of further research on diagnostic crossover from obesity to atypical
      anorexia nervosa.

PMID- 20054206
TI  - Prevalence of obesity in a Saudi obstetric population.
AB  - OBJECTIVE: To estimate the prevalence of obesity and its determinants during the
      first month of gestation in Saudi women. METHODS: Retrospective chart review of
      measured BMI in Al-Hassa, the largest province in Saudi Arabia, in 2007. Data
      were collected from records of 791 (72.6% of 1,089) pregnant women registered for
      prenatal care. RESULTS: Height shows a normal Gaussian distribution, whereas
      weight is skewed positively (skewness of 0.77). The prevalence of underweight,
      normal weight, overweight, obesity, and extreme obesity (BMI > 40 kg/m(2)) were
      8.5, 39.3, 23.6, 23.9, and 4.7%, respectively. Logistic regression revealed that
      the most important significant independent predictors of obesity are parity of 4
      and more (odds ratio (OR) = 5.8) and urban residence (OR = 4.9). CONCLUSION:
      Overweight, obesity, and extreme obesity are common (>52%) among pregnant women
      in Saudi Arabia. Health education to control body weight before pregnancy is
      warranted.

PMID- 20054207
TI  - A small step for obesity but a great leap in the wrong direction for mankind.

PMID- 20054208
TI  - Physician-diagnosed obesity in German 6- to 14-year-olds. Prevalence and
      comorbidity of internalising disorders, externalising disorders, and sleep
      disorders.
AB  - OBJECTIVE: This study analyses whether children with obesity have an increased
      risk of internalising disorders, externalising disorders, and sleep disorders
      compared to children without physician-diagnosed obesity. METHOD: The study
      included 156,948 children aged between 6 and 14 years. We analysed data of a
      German national health insurance company concerning the rates of the physician
      diagnosed ICD-10 disorders of obesity and psychiatric disorders. RESULTS: Greater
      odds for externalising disorders (odds ratio (OR) = 1.64), internalising
      disorders (OR = 2.00), sleep disorders (OR = 1.87), and a stay in hospital (OR =
      1.44) were found among children with physician-diagnosed obesity compared to
      children without physician-diagnosed obesity. The increased ORs were higher in
      girls with obesity compared to boys with obesity for externalising disorders (OR
      = 1.91 vs. 1.52) and internalising disorders (especially anxiety, OR = 2.15 vs.
      1.43). According to age group, the increased OR was highest in young adolescents
      (12- to 14-year-olds) with obesity compared to younger children with obesity for
      internalising disorders (especially anxiety, OR = 2.32 vs. 1.59 and 1.43).
      CONCLUSION: For obesity prevention and obesity intervention, it is important to
      understand comorbid health problems as well as potential interindividual
      influence factors (such as gender or age), both of which should be a focus in
      respective programmes.

PMID- 20054209
TI  - Older members perform better in an internet-based behavioral weight loss program
      compared to younger members.
AB  - BACKGROUND: New technology offers increased opportunities for weight control.
      However, it is not clear whether older people with less computer training can
      make use of this tool. Our objective was to examine how members above the age of
      65 years performed in an internet-based behavioral weight loss program, compared
      to younger members. METHODS: Data from members (n = 23,233) of an internet-based
      behavioral weight loss program were analyzed. We restricted our study to active
      participants accessing the weight club, during a 6-month period (n = 4,440). The
      number of logins, food intake, and weight records were examined. Participants
      were divided into age tertiles separately for men and women. The oldest tertile
      was further subdivided into two groups: above and below the age of 65 years.
      RESULTS: Participants aged 65 or older were more likely to remain active in the
      weight club for at least 6 months compared to younger age groups. They had the
      highest frequency of recordings of food intake and current weight. Among women,
      those older than 65 years had on average the highest percentage of weight loss
      (5.6 kg, 6.8%). Men above 65 years of age had the highest number of logins, on
      average 161 times during the 6-month period. CONCLUSION: Older participants are
      performing equally well or even better in an internet-based behavioral weight
      loss program than younger participants. Internet-based programs could be a
      promising and attractive option for older adults requiring assistance in losing
      weight.

PMID- 20054210
TI  - Heterodimerization of hypothalamic G-protein-coupled receptors involved in weight
      regulation.
AB  - BACKGROUND: Melanocortin 3 and 4 receptors (MC3R and MC4R) are known to play an
      essential role in hypothalamic weight regulation. In addition to these two G
      protein-coupled receptors (GPCRs), a huge number of other GPCRs are expressed in
      hypothalamic regions, and some of them are involved in weight regulation. So far,
      homodimerization was shown for a few of these receptors. Heterodimerization of
      unrelated receptors may have profound functional consequence but
      heterodimerization of GPCRs involved in weight regulation was not reported yet.
      METHODS: A selective number of hypothalamically expressed GPCRs were cloned into
      a eukaryotic expression vector. Cell surface expression was demonstrated by an
      ELISA approach. Subcellular distribution was investigated by confocal laser
      microscopy. A sandwich ELISA and fluorescence resonance energy transfer (FRET)
      were used to determine protein-protein interaction. RESULTS: Via sandwich ELISA
      and FRET approach we could demonstrate a robust interaction of the MC4R with
      GPR7, both of which are expressed in the hypothalamic nucleus paraventricularis.
      Moreover, we determined a strong interaction of MC3R with the growth hormone
      secretagogue receptor expressed in the nucleus arcuatus. CONCLUSION:
      Identification GPCR heterodimerization adds to the understanding of the
      complexity of weight regulation and may provide important information to develop
      therapeutic strategies to treat obesity.

PMID- 20054211
TI  - Impact of weight reduction on eating behaviors and quality of life: Influence of
      the obesity degree.
AB  - BACKGROUND: To examine the effects of a short-term weight reducing program on
      body composition, eating behaviors, and health-related quality of life (HRQL) of
      sedentary obese women characterized by different obesity degrees. METHODS: 44
      women with a BMI under 34.9 kg/m(2) and 39 women with a BMI above 35 kg/m(2) were
      studied. Fat mass and lean mass (electrical bioimpedance), eating behaviors
      (Three-Factor Eating Questionnaire), and HRQL (36-item short form, SF-36,
      questionnaire) were determined before and after weight loss. RESULTS:
      Disinhibition and hunger scores and their subscales decreased after weight loss
      in both groups (0.0001 < p < 0.04). Restriction increased after weight reduction
      in all women (p = 0.02). Among the five restriction subscales, flexible
      restriction increased in women with a BMI above 35 kg/m(2) (p = 0.008), whereas
      rigid restraint and avoidance of fattening foods increased in both groups (0.006
      < p < 0.02). SF-36 Mental Component Score increased after weight loss in all
      women (p < 0.0001). CONCLUSION: A 3week weight reducing program changes selected
      eating behaviors and components of HRQL, irrespective of women's obesity degree.
      Data suggest that women with a BMI above 35 kg/m(2) could have a better weight
      control in the long term because of their higher flexible restriction after
      weight loss when compared to those whose BMI was under 34.9 kg/m(2).

PMID- 20054212
TI  - Waist to height ratio is a simple and effective obesity screening tool for
      cardiovascular risk factors: Analysis of data from the British National Diet And
      Nutrition Survey of adults aged 19-64 years.
AB  - OBJECTIVE AND METHOD: To analyse data from the nationally representative National
      Diet and Nutrition Survey (NDNS) collected in 2000/2001 and to investigate how
      the BMI and two proxy indicators of central fat distribution, namely the waist
      circumference and the waist to height ratio (WHtR), are associated with each
      other and with cardiovascular disease (CVD) risk factors. RESULTS: Screening
      health risk by BMI alone would 'miss' 35% of men and 14% of women who are within
      the normal BMI range (18.5-25 kg/m(2)) but have central fat distribution, defined
      by WHtR > 0.5. In the total population this equates to 17% of all men and 6% of
      all women who would be inadequately screened by BMI alone. Compared to BMI, WHtR
      was more closely associated with CVD risk factors among both men and women.
      Furthermore, in a combined analysis of men and women, central fat distribution
      with a normal BMI was associated with higher levels of CVD risk factors than
      being overweight without central fat distribution. CONCLUSION: WHtR is a simple
      and effective, non-invasive screening tool for CVD risk factors. Our proposed
      boundary value of 0.5 translates into a simple public health message: 'Keep your
      waist circumference to less than half your height'.

PMID- 20054213
TI  - Influence of changes in body composition and adaptive thermogenesis on the
      difference between measured and predicted weight loss in obese women.
AB  - BACKGROUND: There is a difference between measured and predicted weight loss in
      obese patients. This might be explained by the composition of weight loss,
      adaptive thermogenesis, or poor compliance. PATIENTS AND METHODS: 48 overweight
      and obese female patients (31.5 +/- 6.1 years; BMI 35.4 +/- 4.4 kg/m(2)) were
      investigated before and 13.9 +/- 2.4 weeks after dietary treatment (1,000
      kcal/day). Body composition was measured by air-displacement plethysmography and
      resting energy expenditure (REE) by indirect calorimetry. Physical activity was
      assessed using electronic pedometers in order to calculate total energy
      expenditure from REE and physical activity level (PAL). Fat mass (FM) and fat
      free mass (FFM) were converted into caloric equivalents using 9.45 kcal/g FM and
      1.13 kcal/g FFM. Predicted weight loss was calculated by Wishnofsky's '7,700
      kcal/kg rule'. RESULTS: Weight (-8.4 +/- 3.9 kg; p < 0.001), FM (-7.8 +/- 3.6 kg;
      p < 0.001), and FFM (-0.6 +/- 2.0 kg; p < 0.05) decreased with caloric
      restriction. Measured weight loss was only 44% of the predicted value. Since FM
      contributed to 87% of weight loss, the energy deficit/kg weight loss was
      considerably higher (9,098 +/- 2,349 kcal/kg) than the assumed 7,700 kcal/kg.
      Adaptive thermogenesis after weight loss was significant in 26 of 48 women (-3.2
      +/- 1.2 kcal per kg FFM; p < 0.001). CONCLUSION: 14% of the difference between
      measured and predicted weight loss was explained by the higher proportion of FM
      in weight loss and 38% by adaptive thermogenesis (in 54% of the women). Thus,
      poor compliance was responsible for about 50% of the difference between measured
      and predicted weight loss only.

PMID- 20054214
TI  - Efficacy of a screening procedure to identify potentially disruptive participants
      in an immersion program for the treatment of adolescent obesity.
AB  - BACKGROUND: This study examined the efficacy of the red flag screening procedure,
      an approach used in a largescale immersion program for the treatment of
      adolescent obesity (Wellspring Camps). The intention of the red flag screening
      was to screen out potentially highly disruptive applicants, provide an impetus
      for additional support when high-risk campers were admitted, and help parents
      develop appropriate expectations. When compared to non-flagged peers, red-flagged
      campers who attended camp were expected to be sent home early more frequently.
      METHODS: Wellspring's admissions coordinators 'red-flagged' potential campers
      whose enrollment forms showed evidence of a history of psychological distress,
      major medical challenges, and/or developmental delays; a licensed psychologist
      then determined whether or not to admit the child after talking with the
      identified applicant, parents, and health care providers. 554 overweight young
      people attended three Wellspring Camps in the summer of 2007 (445 females, 109
      males, mean age = 15.8 years, mean BMI = 35.6 kg/m(2), mean % overweight =
      66.7%). RESULTS: 8.7% of applicants were red-flagged (n = 48), and 8% of all of
      the campers (n = 44) were dismissed prematurely. As expected, a much higher
      percentage of red-flagged campers who were admitted to camp were dismissed
      prematurely (31,3% of the red-flagged campers) than were non-flagged campers
      (5,1%; p < 0.0005). CONCLUSION: These findings support the efficacy of
      Wellspring's red flag screening procedure. While further improvements can be
      made, such a tool may be useful to other immersion programs.

PMID- 20054215
TI  - Energy homoeostasis: The roles of adipose tissue-derived hormones, peptide YY and
      Ghrelin.
AB  - This review discusses the physiology of the hormones leptin, adiponectin,
      resistin, peptide YY, and ghrelin and how each of these contributes to energy
      homoeostasis, weight regulation, and the pathogenesis of obesity. The
      relationship these hormones have with insulin and insulin resistance is also
      discussed, and the potential therapeutic use of each of these hormones is also
      considered.

PMID- 20054216
TI  - Hypothalamic lipids and the regulation of energy homeostasis.
AB  - The hypothalamus is a specialised area in the brain that integrates the control
      of energy homeostasis, regulating both food intake and energy expenditure. The
      classical theory for hypothalamic feeding control is mainly based on the
      relationship between peripheral signals and neurotransmitters/neuromodulators in
      the central nervous system. Thus, hypothalamic neurons respond to peripheral
      signals, such as hormones and nutrients, by modifying the synthesis of
      neuropeptides. Despite the well-established role of these hypothalamic networks,
      increasing evidence indicates that the modulation of lipid metabolism in the
      hypothalamus plays a critical role in feeding control. In fact, the pharmacologic
      and genetic targeting of key enzymes from these pathways, such as AMP-activated
      protein kinase, acetyl-CoA carboxylase, carnitine palmitoyltransferase 1, fatty
      acid synthase, and malonyl-CoA decarboxylase, has a profound effect on food
      intake and body weight. Here, we review what is currently known about the
      relationship between hypothalamic lipid metabolism and whole body energy
      homeostasis. Defining these novel mechanisms may offer new therapeutic targets
      for the treatment of obesity and its associated pathologies.

PMID- 20054217
TI  - Brown fat - hotting up again.

PMID- 20054218
TI  - Look into the future through the past.

PMID- 20054219
TI  - Raised adolescent body mass index predicts the development of adiposity and a
      central distribution of body fat in adulthood: a longitudinal study.
AB  - OBJECTIVE: To test the hypothesis that adolescent body mass index (BMI) tracks
      into adulthood and can be used as a predictor of obesity and/or central adiposity
      in adulthood. METHOD: A prospective cohort study following up 111 female and 84
      male subjects who participated in dietary and anthropometric surveys when aged 12
      years (in 1979-1981) and 33 years (in 2000-2001). At both time points, height and
      weight were measured and BMI calculated. At 33 years, waist circumference (WC)
      and hip circumference were also measured and waist-to-hip ratio (WHR) calculated.
      RESULTS: In the male and female participants, BMI at 12 years was associated
      significantly with BMI at 33 years (R = 0.58 and 0.53, respectively, both p <
      0.01) and WC at 33 years (R = 0.58 and 0.53, both p < 0.01). The probability of
      being an obese adult increased with rising adolescent BMI: normal weight male
      (BMI < 20.89 kg/m(2)) and female subjects (BMI < 21.20 kg/m(2)) at 12 years had a
      20% and a 7% chance of being obese at 33 years, respectively; the probabilities
      for obese male (BMI > or =25.58 kg/m(2)) and female subjects (BMI > or =26.05
      kg/m(2)) were 83 and 64%. The corresponding probability of becoming centrally
      obese (measured by WC) increased from 17 and 16% in male and female subjects of a
      normal weight to 58 and 59% in those being obese. CONCLUSIONS: Adolescent BMI is
      a good predictor of adult BMI and WC and the likelihood of becoming obese and/or
      centrally obese in adulthood.

PMID- 20054220
TI  - Tracking of dietary intake and factors associated with dietary change from early
      adolescence to adulthood: the ASH30 study.
AB  - OBJECTIVE: This paper describes the tracking of food intake from adolescence to
      adulthood according to location as an adult (at the time of the follow-up study)
      and gender. Additionally this paper explores factors associated with change in
      food intake. METHOD: Two 3-day food diaries, demographic and socio-economic
      information were collected in 1980 and 2000 from the same 198 participants (81
      male, 117 female). Foods consumed were assigned to the five categories in The
      Balance of Good Health (BGH) food model. The tracking of food intake was assessed
      using Pearson correlation analyses. In 2000 two questionnaires were completed.
      Demographic and key attributional factors, derived from closed and open-ended
      responses to the questionnaire, were compared with measured change using
      regression analysis. RESULTS: There was significant tracking of intake by food
      group from adolescence to adulthood according to location as an adult and gender.
      Eight combinations of descriptive variables and questionnaire factors were
      associated with change in intake of four of the five BGH food groups. CONCLUSION:
      Between adolescence and adulthood, dietary tracking is influenced by variables
      including gender and location. Attributions for change in food intake were
      associated with measured changes in food intake. In order to support healthier
      eating habits, it is important to be aware of factors contributing to changes in
      food intake, such as parental influences and perceived influences of time and
      work.

PMID- 20054221
TI  - Fat intake and weight development from 9 to 16 years of age: the European youth
      heart study - a longitudinal study.
AB  - OBJECTIVE: The literature on associations between fat intake and weight
      development among both children and adults is inconsistent, even if it is
      generally assumed that a high dietary fat intake is a major determinant of
      obesity. The present study aimed at investigating the association between fat
      intake and weight development among a cohort of children aged 9-10 years at
      baseline and 15-16 years at follow-up, and, further, at investigating whether
      parents' obesity is modifying the association. METHOD: Among 384 subjects aged 9
      years, data on dietary intake, BMI z-score, physical activity, inactivity,
      parents' social status, parents' body mass index, child birth weight, and status
      of puberty was obtained in 1997. Weight and height was measured both at baseline
      and at 6-year follow-up, and BMI z-score was calculated. Linear regression was
      used to assess the role of fat intake on subsequent weight change between 1997
      and 2003 with the above-mentioned variables as confounders, in 3 different models
      and for each sex separately. RESULTS: The analysis showed no relation between fat
      intake (both absolute intake and fat energy percent) at 9 years and subsequent 6
      year weight change. Only BMI z-score at baseline had a significant relation to
      weight change for both sexes, and number of obese parents had significant
      relation to weight change in girls. Number of overweight parents did not modify
      the association between fat intake and weight change. CONCLUSION: This study was
      unable to find a relation between fat intake and 6-year weight change among 9
      year-old children. No interaction was seen between number of overweight parents
      on the relation between fat intake and subsequent weight change.

PMID- 20054222
TI  - Body mass trajectory, energy balance, and weight loss as determinants of health
      and mortality in older adults.
AB  - The relationship between body mass (usually measured as BMI in kg/m(2)) and
      healthy longevity is a major focus of study in the nutrition and aging field.
      Over-nutrition now rivals frailty as the major nutritional concern; the number of
      older adults who are obese has increased dramatically in the past 3 decades.
      While obesity exacerbates a host of life-threatening, age-related chronic
      diseases, a somewhat paradoxical finding is that being somewhat overweight in old
      age appears to be a benefit with regard to longevity. In our recently completed
      systematic review of randomized controlled weight reduction trials, we found that
      weight loss interventions in overweight/obese older subjects led to significant
      benefits for those with osteoarthritis, coronary heart disease, and type 2
      diabetes mellitus, while having slightly negative effects on bone mineral density
      and lean body mass. In contrast to this finding, the preponderance of
      epidemiological evidence indicates that higher BMIs are associated with increased
      survival after age 65 years. Because of this contradictory state of the science,
      there is a critical need for further study of the relationship of weight and
      weight loss/gain to health in the later years of life.

PMID- 20054224
TI  - Tracking of physical activity from childhood to adulthood: a review.
AB  - The aim of the article was to review studies on the tracking of physical activity
      in all phases of life from childhood to late adulthood. The majority of the
      studies have been published since 2000. The follow-up time in most studies was
      short, the median being 9 years. In men, the stability of physical activity was
      significant but low or moderate during all life phases and also in longterm
      follow-ups. In women, the tracking was lower and in many cases non-significant.
      Among both sexes, stability seems to be lower in early childhood than in
      adolescence or in adulthood and lower in transitional phases, such as from
      childhood to adolescence or from adolescence to adulthood, than in adulthood.
      However, the differences in the stability of physical activity between age groups
      and between different phases of life were small. The number of tracking studies
      utilising objective methods to measure physical activity was so small that
      systematic differences in stability between self-report and objective methods
      could not be determined. A factor which caused differences in tracking results
      was the adjustment of correlations for measurement error and other error
      variance. Adjusted coefficients were clearly higher than unadjusted ones.
      However, adjustment was done only in very few studies. If the different methods
      used for estimating habitual physical activity and the failure to control for
      important covariates in studies of tracking are taken into account, physical
      activity appears to track reasonably well also in the longer term, for example
      from adolescence to adulthood. The results of the tracking studies support the
      idea that the enhancement of physical activity in children and adolescents is of
      great importance for the promotion of public health.

PMID- 20054223
TI  - Weight, dietary behavior, and physical activity in childhood and adolescence:
      implications for adult cancer risk.
AB  - Lifestyle factors related to energy balance, including weight, dietary behavior
      and physical activity, are associated with cancer risk. The period of childhood
      and growth into adolescence and early adulthood may re-present a 'cumulative
      risk' for later adult-onset cancers. We review a number of epidemiologic studies
      that have examined associations among childhood and adolescent body size, diet,
      and physical activity with adult cancer risk. These studies suggest that
      unhealthy behaviors that develop early in life and persist over time may increase
      the risk of some cancer types, such as premenopausal breast, ovarian,
      endometrial, colon and renal cancer, adversely affect cancer-related morbidities,
      and increase mortality. Continued research is needed to further determine and
      refine how timing and degree of such exposures in early childhood and adolescence
      relate to adult cancer risk. Presently, sufficient evidence suggests a continued
      need for stronger primary prevention in cancer and obesity research via modified
      lifestyle behaviors earlier in the developmental spectrum, i.e. during childhood
      and adolescence.

PMID- 20054225
TI  - Genetics of tracking of body mass index from birth to late middle age: evidence
      from twin and family studies.
AB  - The persistence of obesity from early childhood to late middle age is well known.
      We reviewed the results from existing genetic studies on tracking of BMI to
      discover how much genetic and environmental factors contribute to this tracking
      of obesity. In total, we found 5 genetic longitudinal studies on childhood
      obesity and 8 on obesity in adulthood. One was an adoption study, 3 were family
      studies, and 9 were twin studies. All were based on Caucasian populations, and
      one included genetic level information (the FTO gene). Strong genetic continuity
      in BMI was found from early childhood to onset of adulthood. Although new genetic
      factors started to affect BMI during the growth period, genetic correlations
      remained high. Evidence of the effect of common environment on the tracking of
      BMI during childhood was also found. The heritability estimates reported in twin
      studies ranged from 0.57 to 0.86 for the trend of BMI from early adulthood to
      late middle age. The three family studies gave lower estimates. Important
      unresolved questions are the genetics of BMI change in old age, the genetics of
      body composition change, the genetic architecture of tracking of obesity in
      ethnic groups other than Caucasians, and the interplay between genes and
      environment underlying the development and tracking of obesity.

PMID- 20054226
TI  - Impact of depression on diabetes mellitus.

PMID- 20054227
TI  - Relationship between anthropometry and motor abilities at pre-school age.
AB  - OBJECTIVE: Little is known to date about the relationship between poor motor
      abilities and overweight or obese pre-school children. Thus, this study examined
      the association between motor abilities and weight status in 1,228 kindergarten
      children (45.8% female). METHOD: Anthropometric data were assessed; age 4.7 + or 
      1.0 years; height 108.6 + or - 8.0 cm; weight 19.1 + or - 3.6 kg; BMI 16.1 + or 
      1.5 kg/m(2). The modified Karlsruher Motor Ability Screening Test was carried
      out to determine the motor abilities of speed strength, muscular endurance,
      coordination, flexibility, and speed. RESULTS: Based on the German BMI reference
      values, 3.5% of the children were obese, 9.6% overweight, 83.4% normal weight,
      and 3.5% underweight. During various test tasks, below-average motor abilities
      were discovered in 44.0-47.3%. In all age groups, overweight and obese children
      did not differ from their normal and underweight counterparts; except for
      underweight children which fared worse in flexibility. CONCLUSION: In contrast to
      former studies with first graders, overweight or obese pre-school children did
      not possess worse motor abilities than normal weight children. However, the high
      number of overweight children and motor deficits suggests that preventive
      measures should start at this early age.

PMID- 20054228
TI  - Depression and anxiety: their predictive function for weight loss in obese
      individuals.
AB  - OBJECTIVE: To investigate the impact of current mental disorders on weight loss
      with special consideration of depressive and/or anxiety disorders as well as
      binge eating behavior in obese individuals undergoing different weight loss
      treatments. METHODS: Three different samples of obese individuals were
      investigated in a prospective, longitudinal study: participants in a conventional
      weight loss treatment program (CONV TREAT; n = 250), obesity surgery patients
      (OBES SURG; n = 153), and obese control individuals (OC; n = 128). Current mental
      disorders and BMI were assessed at baseline and at 4-year follow-up. RESULTS:
      OBES SURG patients with a depressive and/or anxiety disorder lost significantly
      less weight compared with those without a comorbid mental diagnosis. This result
      was not detected for CONV TREAT participants. A trend to gain weight was seen in
      OC participants with a depressive and/or anxiety disorder, whereas OC
      participants without current mental disorders at baseline lost some weight. Binge
      eating behavior at baseline did not predict weight loss at 4-year followup.
      CONCLUSIONS: These results underline the importance of addressing current
      depressive and anxiety disorders in obese patients, especially when such patients
      are undergoing obesity surgery.

PMID- 20054229
TI  - Gene-gene interaction between APOA5 and USF1: two candidate genes for the
      metabolic syndrome.
AB  - OBJECTIVE: The metabolic syndrome, a major cluster of risk factors for
      cardiovascular diseases, shows increasing prevalence worldwide. Several studies
      have established associations of both apolipoprotein A5 (APOA5) gene variants and
      upstream stimulatory factor 1 (USF1) gene variants with blood lipid levels and
      metabolic syndrome. USF1 is a transcription factor for APOA5. METHODS: We
      investigated a possible interaction between these two genes on the risk for the
      metabolic syndrome, using data from the German population-based KORA survey 4
      (1,622 men and women aged 55-74 years). Seven APOA5 single nucleotide
      polymorphisms (SNPs) were analyzed in combination with six USF1 SNPs, applying
      logistic regression in an additive model adjusting for age and sex and the
      definition for metabolic syndrome from the National Cholesterol Education
      Program's Adult Treatment Panel III (NCEP (AIII)) including medication. RESULTS:
      The overall prevalence for metabolic syndrome was 41%. Two SNP combinations
      showed a nominal gene-gene interaction (p values 0.024 and 0.047). The effect of
      one SNP was modified by the other SNP, with a lower risk for the metabolic
      syndrome with odds ratios (ORs) between 0.33 (95% CI = 0.13-0.83) and 0.40 (95%
      CI = 0.15-1.12) when the other SNP was homozygous for the minor allele.
      Nevertheless, none of the associations remained significant after correction for
      multiple testing. CONCLUSION: Thus, there is an indication of an interaction
      between APOA5 and USF1 on the risk for metabolic syndrome.

PMID- 20054230
TI  - Longitudinal analysis of leptin variation during weight regain after weight loss
      in obese children.
AB  - OBJECTIVE: This study assessed if lower than predicted serum leptin
      concentrations seen during weight loss persisted during weight regain, with
      possible implications for weight control. METHODS: 115 children were investigated
      during a 12-week weight loss program. 90 children completed the program, and 68
      children entered a follow-up program spanning 28 months. Measurements were
      performed at baseline and day 82 as well as at months 10, 16, and 28. Height,
      weight, body composition, Tanner stages, testicular size, and serum
      concentrations of leptin, and insulin were measured at all time points. RESULTS:
      Children with the greatest increases in BMI standard deviation score (SDS)
      exhibited the largest leptin increments. The disproportionate reduction of leptin
      seen during weight loss recovered after weight loss. Leptin increases mirrored
      increases in BMI SDS during weight regain, and the leptin-BMI SDS relationship
      seen during follow-up resembled the baseline leptin-BMI SDS relationship.
      CONCLUSION: Proportional increases of leptin and BMI SDS during weight regain
      suggests an intact leptin response during re-accumulation of fat. Following the
      pronounced reduction of leptin during weight loss, leptin levels were restored
      during weight regain to an extent where leptin levels were comparable with those
      at baseline, which is indicative of an inefficient lipostatic control exerted by
      leptin during weight regain.

PMID- 20054231
TI  - Obesity and physical inactivity: the relevance of reconsidering the notion of
      sedentariness.
AB  - The population statistics of most countries of the world are indicating that
      industrialization and computerization have been associated with an increase in
      sedentariness and more recently with a significant shift from healthy weight to
      overweight. In general, this change in the overweight/obesity prevalence is
      attributed by health professionals to suboptimal diet and physical activity
      practices. However, recent data raised the possibility that excess weight gain
      might also be the outcome of changes imposed by our '24-hour', hectic lifestyle.
      Parallel to an increase in body weight, one has observed a reduction in sleep
      time and an increase in knowledge-based work (KBW) that appear as a growing
      necessity in a context of economic competitiveness and globalization. Sleep and
      cognitive work both exert a trivial effect on energy expenditure and may thus be
      considered as sedentary activities. However, their respective effect on energy
      intake is opposite. Indeed, an increase in the practice of the most sedentary
      activity, i.e. sleep, is associated with a hormonal profile facilitating appetite
      control whereas KBW appears as a stimulus favoring a significant enhancing effect
      on food intake. Television viewing is another example of sedentary activity that
      has been shown to increase the intake of high-density foods. These observations
      demonstrate that the modern way of living has favored a change in human
      activities whose impact goes well beyond what has traditionally been attributed
      to a lack of physical exercise. Therefore, we will need to reconsider the notion
      of 'sedentariness' which includes several activities having opposing effects on
      energy balance.

PMID- 20054232
TI  - Grifola frondosa water extract alleviates intestinal inflammation by suppressing
      TNF-alpha production and its signaling.
AB  - TNF-alpha is a major cytokine involved in inflammatory bowel disease (IBD). In
      this study, water extract of Grifola frondosa (GFW) was evaluated for its
      protective effects against colon inflammation through the modulation of TNF-alpha
      action. In coculture of HT-29 human colon cancer cells with U937 human monocytic
      cells, TNF-alpha-induced monocyte adhesion to HT-29 cells was significantly
      suppressed by GFW (10, 50, 100 micg/ml). The reduced adhesion by GFW correlated
      with the suppressed expression of MCP-1 and IL-8, the major IBD-associated
      chemokines. In addition, treatment with GFW significantly suppressed TNF-alpha
      induced reactive oxygen species production and NF-kappaB transcriptional activity
      in HT-29 cells. In differentiated U937 monocytic cells, LPS-induced TNF-alpha
      production, which is known to be mediated through NF-kappaB activation, was
      significantly suppressed by GFW. In an in vivo rat model of IBD, oral
      administration of GFW for 5 days (1 g/kg per day) significantly inhibited the
      trinitrobenzene sulfonic acid (TNBS)-induced weight loss, colon ulceration,
      myeloperoxidase activity, and TNF-alpha expression in the colon tissue. Moreover,
      the effect of GFW was similar to that of intra-peritoneal injection of 5
      aminosalicylic acid (5-ASA), an active metabolite of sulfasalazine, commonly used
      drug for the treatment of IBD. The results suggest that GFW ameliorates colon
      inflammation by suppressing production of TNF-alpha as well as its signaling
      through NF-kappaB leading to the expression of inflammatory chemokines, MCP-1 and
      IL-8. Taken together, the results strongly suggest GFW is a valuable medicinal
      food for IBD treatment, and thus may be used as an alternative medicine for IBD.

PMID- 20054233
TI  - Early growth response protein 1 acts as an activator of SOX18 promoter.
AB  - Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of
      vascular development playing a role in endothelial cell specification or
      differentiation, angiogenesis and atherogenesis. The aim of this study was to
      perform comprehensive functional characterization of the human SOX18 promoter,
      including determination of transcription start point (tsp) and identification of
      control elements involved in the regulation of SOX18 gene expression, with an
      emphasis on angiogenesis-related transcription factors. Analyses were performed
      in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an
      endothelial model system. We have determined unique tsp of SOX18 gene, located
      172 nucleotides upstream from ATG codon. Further, we have shown that SOX18
      promoter region, -726 to -89 bp relative to tsp, contains positive cis-regulatory
      element(s) that stimulates SOX18 promoter activity, while region -89 to+166
      represents the minimal promoter. Within this region we have recognized the
      presence of essential element(s), positioned from -89 to +29, which harbors
      cluster of three putative early growth response 1 (EGR1) binding sites. By in
      vitro binding assays and functional analyses we have shown that these three
      putative binding sites are functionally relevant and sufficient for EGR1-induced
      SOX18 transcription. Mutations of these binding sites significantly impaired
      activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the
      importance of these regulatory elements for SOX18 promoter activity in
      endothelial setting. By data presented in this study, we have established SOX18
      as a novel target gene regulated by EGR1 transcription factor, thus providing the
      first functional link between two transcription factors previously shown to be
      involved in the control of angiogenesis.

PMID- 20054234
TI  - Intramarrow injection of beta-catenin-activated, but not naive mesenchymal
      stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow.
AB  - Bone marrow mesenchymal stromal cells (MSCs) have been implicated in the
      microenvironmental support of hematopoietic stem cells (HSCs) and often co
      transplanted with HSCs to facilitate recovery of ablated bone marrows. However,
      the precise effect of transplanted MSCs on HSC regeneration remains unclear
      because the kinetics of HSC self-renewal in vivo after co-transplantation has not
      been monitored. In this study, we examined the effects of intrafemoral injection
      of MSCs on HSC self-renewal in rigorous competitive repopulating unit (CRU)
      assays using congenic transplantation models in which stromal progenitors (CFU-F)
      were ablated by irradiation. Interestingly, naive MSCs injected into femur
      contributed to the reconstitution of a stromal niche in the ablated bone marrows,
      but did not exert a stimulatory effect on the in-vivo self-renewal of co
      transplanted HSCs regardless of the transplantation methods. In contrast, HSC
      self-renewal was four-fold higher in bone marrows intrafemorally injected with
      beta-catenin-activated MSCs. These results reveal that naive MSCs lack a
      stimulatory effect on HSC self-renewal in-vivo and that stroma must be activated
      during recoveries of bone marrows. Stromal targeting of wnt/beta-catenin signals
      may be a strategy to activate such a stem cell niche for efficient regeneration
      of bone marrow HSCs.

PMID- 20054235
TI  - Reverse genetic platform for inactivated and live-attenuated influenza vaccine.
AB  - Influenza vaccine strains have been traditionally developed by annual
      reassortment between vaccine donor strain and the epidemic virulent strains. The
      classical method requires screening and genotyping of the vaccine strain among
      various reassortant viruses, which are usually laborious and time-consuming. Here
      we developed an efficient reverse genetic system to generate the 6:2 reassortant
      vaccine virus from cDNAs derived from the influenza RNAs. Thus, cDNAs of the two
      RNAs coding for surface antigens, haemagglutinin and neuraminidase from the
      epidemic virus and the 6 internal genes from the donor strain were transfected
      into cells and the infectious viruses of 6:2 defined RNA ratio were rescued. X-31
      virus (a high- growth virus in embryonated eggs) and its cold-adapted strain X-31
      ca were judiciously chosen as donor strains for the generation of inactivated
      vaccine and live-attenuated vaccine, respectively. The growth properties of these
      recombinant viruses in embryonated chicken eggs and MDCK cell were
      indistinguishable as compared to those generated by classical reassortment
      process. Based on the reverse genetic system, we generated 6+2 reassortant avian
      influenza vaccine strains corresponding to the A/Chicken/Korea/ MS96 (H9N2) and
      A/Indonesia/5/2005 (H5N1). The results would serve as technical platform for the
      generation of both injectable inactivated vaccine and the nasal spray live
      attenuated vaccine for the prevention of influenza epidemics and pandemics.

PMID- 20054267
TI  - Carl Koller Gold Medal Award to Dag Selander atThe 27th Annual Congress of the
      European Society of Regional Anaesthesia and Pain Therapy; Genoa, Italy;
      September 24-27, 2008.

PMID- 20054236
TI  - The p53 target Plk2 interacts with TSC proteins impacting mTOR signaling, tumor
      growth and chemosensitivity under hypoxic conditions.
AB  - Tuberous sclerosis complex 1 (TSC1) inhibits mammalian target of rapamycin
      (mTOR), a central promotor of cell growth and proliferation. The protein product
      of the TSC1 gene, hamartin (referred to as TSC1) is known to interact with Polo
      like kinase 1 (Plk1) in a cell cycle regulated, phosphorylation-dependent manner.
      We hypothesized that the p53 target gene, Plk2, is a tumor suppressor, mediating
      its tumor suppressor function through interactions with TSC1 that facilitate
      TSC1/2 restraint of mTOR under hypoxic stress. We found that human lung tumor
      cells deficient in Plk2 grew larger than control tumors, and that Plk2 interacts
      with endogenous TSC1 protein. Additionally, C-terminal Plk2-GST fusion protein
      bound both TSC1 and TSC2 proteins. TSC1 levels were elevated in response to
      Adriamycin and cells transiently overexpressing Plk2 demonstrated decreased
      phosphorylation of the downstream target of mTOR, ribosomal protein p70S6 kinase
      during hypoxia. Plk2 levels were inversely correlated with cytoplasmic p70S6K
      phosphorylation. Plk2 levels did not increase in response to DNA damage
      (Adriamycin, CPT -11) when HCT 116 and H460 cells were exposed to hypoxia. TSC1
      deficient mouse embryonic fibroblasts with TSC1 added back demonstrated decreased
      S6K phosphorylation, which was further decreased when Plk2 was transiently
      overexpressed. Interestingly, under normoxia, Plk2 deficient tumor cells
      demonstrated increased apoptosis in response to various chemotherapeutic agents
      including CPT -11 but increased resistance to apoptotic death after CPT-11
      treatment under hypoxia, and tumor xenografts comprised of these Plk2-deficient
      cells were resistant to CPT -11. Our results point to a novel Plk2-TSC1
      interaction with effects on mTOR signaling during hypoxia, and tumor growth that
      may enable targeting Plk2 signaling in cancer therapy.

PMID- 20054269
TI  - National and surgical health care expenditures, 2005-2025.
AB  - OBJECTIVE AND BACKGROUND: Health care expenditures for 2005 in the United States
      were $1.9733 trillion and 15.9% of the gross domestic product (GDP). Twenty-nine
      percent of those expenditures were secondary to surgical revenues. Health care
      expenditures are increasing 2(1/2) times the rate of the general US economy and
      are being fed by new technologies, new medications, the aging population, more
      services provided per patient, defensive medicine and little tort reform, the
      insurance system, and the free rider problem, ie, patients are cared for as
      emergencies regardless of insurance coverage and legality, which all have
      contributed to rising health care and surgical expenditures over the last 50
      years. METHODS: The purpose of this study was to project aggregate national
      health care expenditures, aggregate surgical health care expenditures, and the
      United States GDP for the years 2005-2025. Model building and existing state and
      national data were used. Aggregate surgical health care expenditures were
      computed as 29% of aggregate health care expenditures using a unique model
      developed by the late Dr. Francis D. Moore. The model of Dr. Moore which used
      1981 federal data was verified/tested using data from UMDNJ-University Hospital,
      and New Jersey and national data from 2005. From 1965 to 2005 mean health care
      expenditures increased at 4.9% per year, and US GDP increased at a mean of 2.1%
      per year. RESULTS: Aggregate surgical expenditures are expected to grow from $572
      billion in 2005 (4.6% of US GDP) to $912 billion (2005 dollars) in the year 2025
      (7.3% of US GDP). Aggregate health care expenditures are projected to increase
      from $5572 per capita (15.9% of GDP) in 2005 to $8832 per capita (2005 dollars)
      in 2025 (25.2% of US GDP). Both surgery and national health care expenditures are
      expected to expand by almost 60% during the period 2005-2025. Thus, surgical
      health care expenditures by 2025 are likely to be 1/14 of the US economy, and
      health care expenditures will be (1/4) of the US economy. CONCLUSIONS: Real per
      capita GDP growth is relatively flat in the United States. Rising surgical health
      care expenditures and national health care expenditures are a significant issue
      for the US population. Unfortunately, programs at the state and federal level as
      well as private programs, for the last 50 years have not been able to slow the
      growth in health care expenditures. These trends are likely to continue and the
      effects will be: * A change in the US standard of living as surgical and health
      care expenditures become a larger part of the earned dollar per American
      especially with the current volatility of the US economy, * A rise in the cost of
      products made in the United States to pay the rising health care bill with a
      concomitant change in our national and international standard of living, and * An
      increasing debt and increases in federal and state taxes which will be required
      to maintain the current health care system, ie, Medicare, Medicaid, and the
      private health care insurance payment scheme, which has not changed substantially
      over the past 40 to 50 years. Surgeons must look at the incremental benefit of
      new technologies and procedures and determine which to choose if we are to slow
      the growth of surgical health care expenditures.

PMID- 20054270
TI  - Should laparoscopic cholecystectomy be practiced in the developing world?

PMID- 20054271
TI  - Effect of meeting Leapfrog volume thresholds on complication rates following
      complex surgical procedures.
AB  - BACKGROUND: There is limited published data on the relationship between hospital
      volume and postoperative complications. The objectives of the current study are
      to examine the association between hospital volume and complications and also to
      examine the association between complications and in-hospital mortality following
      5 complex surgical procedures. METHODS: The Nationwide Inpatient Sample for years
      2000 to 2003 was used. Patients who underwent coronary artery bypass graft
      (CABG), percutaneous coronary intervention (PCI), elective abdominal aortic
      aneurysm repair (AAA), pancreatectomy (PAN), and esophagectomy (ESO) as primary
      procedures were selected. Hospital volumes were calculated as suggested by the
      Leapfrog Group evidence-based hospital referral criteria. The association between
      hospital volume and complications were examined by multivariable logistic
      regression analyses, adjusting for patient and hospital characteristics. RESULTS:
      A total of 261551 CABG, 573072 PCI, 35104 AAA, 4931 PAN, and 2473 ESO procedures
      were selected for analysis. A total of 580 hospitals performed the CABG
      procedures during the study period in this dataset. The corresponding numbers of
      hospitals for PCI, AAA, PAN, and ESO were 714, 1207, 758, and 555 respectively.
      In-hospital complication rates following CABG, PCI, AAA, PAN, and ESO were
      26.45%, 6.74%, 23.81%, 39.28%, and 46.30%, respectively. High-volume hospitals
      for all the procedures were associated with lower odds for in-hospital mortality
      when compared with low-volume hospitals (P < 0.05). High-volume hospitals were
      associated with significantly lower odds for at least one complication following
      3 of the 5 procedures (PCI, AAA, and PAN) and specifically for significantly
      lower odds for respiratory complications following CABG, AAA, and PAN, digestive
      complications following PAN, hemorrhage/hematoma complications following PCI, and
      septicemia following PCI and PAN when compared with low-volume hospitals (P <
      0.05). CONCLUSION: Lower mortality rates in high-volume hospitals can be partly,
      though not completely, attributed to lower complication rates. Future studies
      must focus on identifying other potential pathways for reduced mortality in high
      volume hospitals.

PMID- 20054272
TI  - The migration of surgeons.
AB  - This study attempted to determine if there were identifiable trends in where
      surgeons moved from and to over time. Physicians, including surgeons, change the
      location of their practices over their careers. If this movement follows economic
      theory that surgeons, like most professionals, seek better economic
      opportunities, then their movements should be toward better markets for their
      services. Using US national data (American Medical Association Masterfile) that
      describes the practice locations of surgeons, this study tracked county-level
      changes of practice location and summarized the characteristics of the places
      surgeons left and those they moved to. The analysis was primarily descriptive
      with linear multivariate regression models constructed to determine the
      characteristics of the surgeons who moved and of the places from and to which
      they moved. Approximately 30,262 (32.1%) of 94,630 actively practicing, post
      training, nonfederal surgeons moved in the 10-year period 1996-2006. The overall
      tendency of movers was to go to places that had more physicians and a better
      overall economic environment. These trends, if they continue, may create pressure
      on access in rural and urban underserved areas.

PMID- 20054273
TI  - Venous thromboembolism risk and prophylaxis in the acute care hospital setting
      (ENDORSE survey): findings in surgical patients.
AB  - OBJECTIVE: To evaluate venous thromboembolism (VTE) risk in patients who
      underwent a major operation, including the use of, and factors influencing,
      American College of Chest Physicians-recommended types of VTE prophylaxis.
      SUMMARY BACKGROUND DATA: The Epidemiologic International Day for the Evaluation
      of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting
      (ENDORSE) survey, conducted in 358 hospitals in 32 countries, reported that
      globally, more than 40% of at-risk patients do not receive VTE prophylaxis.
      Limited data are available regarding VTE prophylaxis practices according to
      surgery type and patient characteristics. METHODS: Patients aged >or=18 years
      undergoing major surgery were included in this prespecified subanalysis. VTE risk
      and use of prophylaxis were determined from hospital medical records according to
      the 2004 American College of Chest Physicians guidelines. Multivariable analyses
      were performed to identify factors associated with VTE prophylaxis use. RESULTS:
      Of the 18,461 patients in ENDORSE who had undergone major surgery, 17,084 (92.5%)
      were at-risk for VTE and 10,638 (62.3%) received prophylaxis. Use of prophylaxis
      varied according to major surgery type from 86.0% for orthopedic surgery to 53.8%
      in urologic/gynecologic and 53.6% in other procedures. Major orthopedic surgery
      was most strongly associated with prophylaxis use (hip replacement: odds ratio
      6.2, 95% confidence interval [CI] 5.0-7.6; knee replacement: odds ratio 5.9, 95%
      CI 4.6-7.8). CONCLUSIONS: The majority of surgical patients are at high-risk for
      VTE. Despite long-standing recognition of the high-risk for VTE in surgical
      patients, thromboprophylaxis remains underutilized.

PMID- 20054274
TI  - Auxiliary liver transplantation for acute liver failure in children.
AB  - OBJECTIVE: The aim of this study is to present the largest experience of
      auxiliary liver transplantation for acute liver failure (ALF) in children over
      the past 19 years. METHODS: Between 1990 and 2009, a total of 128 liver
      transplants were performed on children with ALF. Of these, 20 received auxiliary
      liver transplants (19 were cadaveric and 1 living graft). The recipient median
      age was 12 years (range: 1 -16). Indications for auxiliary partial orthotopic
      liver transplantation were seronegative non-A non-B hepatitis in 16 children,
      drug induced in 2, and 1 autoimmune hepatitis and 1 mushroom poisoning. The
      median waiting time for transplantation was 2 days (range: 1-9). After native
      liver partial hepatectomy, 20 grafts were implanted orthotopically and included 8
      right lobes, 8 left lateral segments, 3 left lobes, and 1 whole liver.
      Regeneration of the native liver was assessed by radiologic, nuclear medicine
      imaging, and histology. Follow-up imaging and biopsies were performed at
      intervals of 3 to 6 months and yearly. RESULTS: Patient survival was 85% at 1, 5,
      and 10 years. There were 3 deaths at a median of 9 days (range: 8-52) post
      transplantation. There was 1 retransplant for chronic rejection 15 months post
      transplantation. There were no biliary or vascular complications. Of 17
      survivors, 14 (82%) have successfully regenerated their native liver and so far
      11 children (65% of the survivors) have been withdrawn from immunosuppression at
      a median time of 23 months (range: 4-106) after transplantation. CONCLUSION:
      Auxiliary partial orthotopic liver transplantation should be considered in
      children presenting with ALF who fulfill criteria for liver transplantation.

PMID- 20054275
TI  - Aggressive surgical resection for hilar cholangiocarcinoma of the left-side
      predominance: radicality and safety of left-sided hepatectomy.
AB  - OBJECTIVES: To evaluate the clinicopathologic outcomes in patients with hilar
      cholangiocarcinoma (HC) after left-sided hepatectomy (L-H). SUMMARY BACKGROUND
      DATA: L-H is indicated as radical surgery for HC, predominantly involving left
      hepatic duct. However, several reports have demonstrated that L-H often results
      in tumor-positive margin and unfavorable prognosis compared with right-sided
      hepatectomy (R-H). METHODS: A total of 224 patients with HC underwent surgical
      resection with curative intent at our institution: L-H for Bismuth-Corlette (B-C)
      type IIIb tumors in 88 patients (39.3%) including 75 left hemihepatectomies and
      13 left trisectionectomies, and R-H mainly for B-C type IIIa and IV tumors in 84
      patients (37.5%). In this study, clinicopathologic outcomes and perioperative
      morbidity and mortality rates after L-H were investigated and compared with those
      after R-H. RESULTS: Histologically negative margin (R0) resection was achieved in
      56 cases (63.6%) with L-H, similar to the results for R-H (58/84, 69.1%).
      However, the R0 resection rate in L-H cases with portal vein (PV) resection was
      lower (11/25, 44.0%), and various types of PV reconstruction were required.
      Proximal ductal stumps and excisional surface at periductal structures were the
      most common sites of positive margins. However, when curative resection was
      achieved, 5-year survival was comparable to that in R-H cases. Furthermore, lower
      mortality was noted in L-H cases, even with left trisectionectomy. Multivariate
      analysis indicated curability and hepatic artery resection as independent
      prognostic factors. CONCLUSIONS: Since L-H is a safe procedure and represents the
      only curative resectional option for type IIIb tumor, aggressive surgical
      resection should be performed even in cases with PV involvement, if R0 resection
      is possible.

PMID- 20054276
TI  - Predictive model of outcome of targeted nodal assessment in colorectal cancer.
AB  - BACKGROUND: Improvement in staging accuracy is the principal aim of targeted
      nodal assessment in colorectal carcinoma. Technical factors independently
      predictive of false negative (FN) sentinel lymph node (SLN) mapping should be
      identified to facilitate operative decision making. PURPOSE: To define
      independent predictors of FN SLN mapping and to develop a predictive model that
      could support surgical decisions. PATIENTS AND METHODS: Data was analyzed from 2
      completed prospective clinical trials involving 278 patients with colorectal
      carcinoma undergoing SLN mapping. Clinical outcome of interest was FN SLN(s),
      defined as one(s) with no apparent tumor cells in the presence of non-SLN
      metastases. To assess the independent predictive effect of a covariate for a
      nominal response (FN SLN), a logistic regression model was constructed and
      parameters estimated using maximum likelihood. A probabilistic Bayesian model was
      also trained and cross validated using 10-fold train-and-test sets to predict FN
      SLN mapping. Area under the curve (AUC) from receiver operating characteristics
      curves of these predictions was calculated to determine the predictive value of
      the model. RESULTS: Number of SLNs (<3; P = 0.03) and tumor-replaced nodes (P <
      0.01) independently predicted FN SLN. Cross validation of the model created with
      Bayesian Network Analysis effectively predicted FN SLN (area under the curve =
      0.84-0.86). The positive and negative predictive values of the model are 83% and
      97%, respectively. CONCLUSION: This study supports a minimum threshold of 3 nodes
      for targeted nodal assessment in colorectal cancer, and establishes sufficient
      basis to conclude that SLN mapping and biopsy cannot be justified in the presence
      of clinically apparent tumor-replaced nodes.

PMID- 20054277
TI  - The effects of smoking and alcohol consumption on age-related hearing loss: the
      Blue Mountains Hearing Study.
AB  - OBJECTIVES: We aimed to investigate the temporal association between smoking or
      alcohol consumption and hearing loss, and to confirm previously published cross
      sectional associations. DESIGN: The Blue Mountains Hearing Study is a population
      based survey of age-related hearing loss conducted in a defined suburban area,
      west of Sydney. Hearing loss was measured in 2956 participants (aged 50+ yrs) and
      was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0, and 4.0 kHz
      >25 dB HL in the better ear (bilateral hearing loss). Alcohol consumption and
      smoking status were measured using an interviewer-administered questionnaire.
      Logistic regression was used to obtain odds ratios (OR) with 95% confidence
      intervals (95% CI) that compared the chances of having hearing loss in
      participants who did or did not smoke or consume alcohol, after adjusting for
      other factors previously reported to be associated with hearing loss. RESULTS:
      The prevalence of hearing loss at baseline was 33.0% (N = 929) and the 5-year
      incidence of hearing loss was 17.9% (N = 156). Cross-sectional analysis
      demonstrated a significant protective association between the moderate
      consumption of alcohol (>1 but < or =2 drinks/day) and hearing function in older
      adults (compared with nondrinkers), OR 0.75 (95% CI, 0.57 to 0.98). Current
      smokers not exposed to occupational noise had a significantly higher likelihood
      of hearing loss after adjusting for multiple variables, OR 1.63 (95% CI, 1.01 to
      2.64). A formal likelihood ratio test demonstrated that the interaction between
      smoking and noise exposure was not significant (p = 0.23). When the joint effects
      of alcohol consumption and smoking on hearing were explored, there was a trend
      for alcohol to have a protective relationship with hearing loss in smokers, but
      this was not statistically significant. However, the 5-year incidence of hearing
      loss was not predicted by either smoking or alcohol consumption. CONCLUSIONS:
      This study confirms previously reported associations between alcohol consumption
      or smoking and prevalent hearing loss, but these were not demonstrated in
      temporal data. Other risk factors could confer greater vulnerability or cause the
      initial damage to hearing. Future large population-based studies, exploring the
      influence of other risk factors on the development of age-related hearing loss
      are warranted.

PMID- 20054278
TI  - Clinical practice for children with mild bilateral and unilateral hearing loss.
AB  - OBJECTIVE: Historically, children with mild bilateral and unilateral hearing loss
      have been reported to experience difficulties related to language and academic
      functioning. In the context of Universal Newborn Hearing Screening, there is an
      increasing focus on determining optimal clinical interventions for this
      population of children. The objectives of this study were to determine the
      prevalence of mild bilateral or unilateral hearing loss identified in a clinical
      population from 1990 to 2006 and to document clinical practices related to
      recommendations and uptake of amplification. DESIGN: This population-based study
      consisted of a detailed retrospective chart review of all children identified
      with mild bilateral or unilateral hearing loss in a Canadian pediatric center
      between 1990 and 2006. Hearing loss and patient characteristics were extracted to
      describe the clinical population. Amplification recommendations and uptake of
      amplification were documented. Clinical decisions regarding amplification
      practices were explored as a function of age of identification and severity of
      hearing loss. RESULTS: A total of 670 children were identified with permanent
      hearing loss during the 16-yr study period, of which 291 were presented with a
      mild bilateral or unilateral hearing loss. Detailed reviews of the 255 available
      medical charts showed that at diagnosis, 178 children presented with mild
      bilateral, 31 with mild bilateral high frequency, and 46 with unilateral hearing
      loss. Eighty percent of children had been referred through conventional medical
      processes before the implementation of universal hearing screening and 20% had
      been exposed to screening. The average age of identification for the entire group
      was 54.2 mos (interquartile range, 30.1 to 76.9 mos). Amplification was
      prescribed for 91.4% of children but there was considerable delay from
      confirmation of hearing loss to amplification for both children identified with
      and without screening. Overall, 54.1% received an initial recommendation for
      amplification and a further 37.3% received a recommendation more than 3 mos after
      hearing loss confirmation. Practice patterns varied according to category of
      hearing loss with 60.1% of children with mild bilateral hearing loss receiving an
      initial recommendation compared with 26.1% of those with unilateral hearing loss.
      Clinical decision making relative to amplification needs was also changed during
      the course of audiologic care. The decision to amplify was significantly related
      to age at identification and degree of hearing loss in the mild bilateral group
      but not in the unilateral group. Although, more than 90% of children received a
      recommendation for amplification, chart documentation revealed that less than two
      thirds of children consistently used their amplification devices. Use of
      amplification did not vary among children with mild bilateral, mild bilateral
      high frequency, and unilateral hearing loss. CONCLUSIONS: : This research
      suggests that there is considerable uncertainty related to clinical
      recommendations of intervention for this population of children. The impact of
      parental indecision regarding the benefits of amplification is unknown. Further
      studies are required to document the potential benefits and factors affecting
      amplification recommendations and use in the current practice environment where
      children with mild bilateral or unilateral hearing loss are identified early
      through newborn hearing screening.

PMID- 20054279
TI  - Slight-mild sensorineural hearing loss in children: audiometric, clinical, and
      risk factor profiles.
AB  - OBJECTIVES: Slight or mild hearing loss has been posited as a factor affecting
      speech, language, learning, and academic outcomes, but the risk factors for
      slight-mild sensorineural hearing loss (SNHL) have not been ascertained. The two
      specific aims for this research were (1) to describe the audiometric and clinical
      characteristics of children identified with slight-mild bilateral SNHL and (2) to
      compare children with slight-mild SNHL with those with normal hearing (NH) with
      respect to potential risk factors for congenital or acquired for hearing loss.
      DESIGN: A cross-sectional cluster sample survey of 6581 children enrolled in
      years 1 and 5 of Australian elementary school was completed. Children were
      screened for slight-mild SNHL, defined as a low- and/or high-frequency pure-tone
      average of 16 to 40 dB HL in the better ear, with air-bone gaps <10 dB. Children
      who did not pass the screen received air and bone conduction threshold and
      tympanometry tests to determine the type and degree of hearing loss. The parents
      of every child who participated in this study completed a questionnaire, before
      the hearing screening, to ascertain possible risk indicators. The questionnaire
      included items regarding the family's demographics, hearing status of family
      members, the presence of risk factors, and parental concern regarding the child's
      hearing. RESULTS: Fifty-five children with slight-mild SNHL and 5490 with NH were
      identified. Of the group with SNHL, 39 children had a slight loss (16 to 25 dB
      HL) and 16 had a mild loss (26 to 40 dB HL). The majority of the losses were
      bilateral and symmetrical, and the mean pure-tone average for the better ear for
      all 55 children was 22.4 dB HL (SD, 5.2). The most prevalent risk factor was
      "neonatal intensive care unit/special care nursery admission," which was reported
      for 12.5% of the SNHL and 8.4% of the NH group. Reported use of personal stereos
      was a significant risk factor with an odds ratio of 1.7 (95% confidence interval
      = 1.0 to 3.0, p = 0.05). The questions relating to parental concern for their
      child's hearing had low sensitivity (<30%) and very low positive predictive
      values (<3%) for detecting slight-mild SNHL. CONCLUSIONS: Slight-mild SNHL had a
      prevalence of 0.88% among the school-aged population sampled, with the majority
      of these children exhibiting bilateral, symmetrical audiometric configurations.
      Conventional risk factors for hearing loss were not strongly predictive of slight
      mild SNHL nor were parental concerns about the child's hearing ability. The
      association between slight-mild SNHL and the parent report of personal stereo use
      suggests that this type of noise exposure may be a risk factor for acquired
      hearing loss. This seems to be the first documentation of such an association in
      a large sample of young children.

PMID- 20054280
TI  - Vestibular-evoked myogenic potential in the prediction of recovery from acute low
      tone sensorineural hearing loss.
AB  - OBJECTIVE: Click and galvanic stimulations of vestibular-evoked myogenic
      potential (c-VEMP and g-VEMP) were applied to measure the interaural difference
      (IAD) of saccular responses in patients with acute low-tone sensorineural hearing
      loss (ALHL). This study intended to explore the relationship between saccular
      asymmetry and final hearing recovery. We hypothesize that greater extent of
      saccular dysfunction may be associated with lesser hearing recovery. DESIGN:
      Twenty-one patients with unilateral ALHL were prospectively enrolled to receive c
      VEMP and g-VEMP tests in a random sequence. The IAD of the saccular responses for
      each patient was measured using three parameters-the raw and corrected amplitudes
      of c-VEMP, and corrected c-VEMP to g-VEMP amplitude ratio (C/G ratio). The IAD
      for each parameter was classified as depressed, normal, or augmented by
      calculating the difference between the affected and unaffected ears and dividing
      by its sum for both ears. RESULTS: After 3 consecutive months of oral medication
      and follow-up, 19 patients displayed a hearing recovery of >50%; only two had a
      recovery of <50%. The significant correlation between the IAD of corrected C/G
      ratios and hearing recovery demonstrated that subjects with depressed responses
      had a worse hearing outcome (percent recovery: 51% [45-80%], median [minimum
      maximum]), compared with those with normal responses, who exhibited the best
      recovery (87% [56-100%]), whereas patients with augmented response showed an
      intermediate recovery (67% [54-100%]; p = 0.02, Kruskal-Wallis test). On the
      contrary, the raw and corrected amplitudes of c-VEMP did not reveal a
      significantly different hearing recovery among the three groups of saccular
      responses. CONCLUSIONS: The extent of saccular dysfunction in ALHL might be
      better explored by combining the results of c-VEMP and g-VEMP. Outcome analysis
      indicated that the corrected C/G ratio might be a promising prognostic factor for
      hearing recovery in ALHL.

PMID- 20054281
TI  - Fecal calprotectin concentration in celiac disease.
AB  - GOALS: We aimed to determine fecal calprotectin (FC) concentration and its
      relation with histopathologic findings of children with celiac disease (CD) and
      to observe the probable alterations under gluten-free diet (GFD). BACKGROUND: As
      FC is regarded as a marker of inflammation in the gastrointestinal tract, we
      hypothesized that it might be increased in untreated CD. STUDY: The study
      included 29 newly diagnosed patients with CD (mean age: 6.6+/-0.6 y) and sex and
      age-matched 10 healthy children. All of the children with CD admitted to the
      hospital were classical form who has chronic diarrhea and failure to thrive. The
      degree of mucosal damage was graded according to the modified Marsh criteria. FC
      concentration was determined by enzyme-linked immunosorbent assay method on
      admission and after 1 year of GFD. RESULTS: Mean FC concentration of children
      with CD on admission and of healthy children were 13.40+/-8.5 and 4.3+/-3.3 mg/L,
      respectively (P=0.004). FC concentration under GFD was 4.6+/-2.7 mg/L and there
      was a significant statistical difference between untreated patients and those
      under GFD for 1 year (P=0.001). There was no statistical difference between FC
      concentration of those under GFD and healthy children (P=0.8). Mean FC
      concentrations of children with total-villous atrophy and partial-villous atrophy
      were significantly different (13.8+/-9.3 mg/L vs. 3.7+/-1.8 mg/L, P=0.005).
      CONCLUSIONS: It was found that FC concentration is increased in childhood CD,
      related to the severity of histopathologic findings and responsive to GFD. The
      pathogenetic mechanism by which FC is increased in CD should be investigated in
      further studies.

PMID- 20054282
TI  - A full solid diet as the initial meal in mild acute pancreatitis is safe and
      result in a shorter length of hospitalization: results from a prospective,
      randomized, controlled, double-blind clinical trial.
AB  - GOALS: To compare the safety and length of hospitalization (LOH) between a full
      solid diet as the initial meal for refeeding after mild acute pancreatitis (AP)
      as compared with 2 other diets. BACKGROUND: In mild AP, the need for fat
      restriction during refeeding has not been studied. It was hypothesized that the
      reintroduction of oral feeding with a full solid diet after mild AP was safe and
      might result in a shorter LOH. STUDY: Subjects with mild AP were randomized to
      receive 1 of 3 diets (clear liquid, soft, or full solid) as the initial meal
      during oral refeeding. Diet progression and hospital discharge were decided by
      the physicians that were not members of trial team. During hospital stay,
      patients were monitored for relapse of pain (primary endpoint), dietary intake,
      LOH (secondary endpoint), and 7 days postdischarge to record pain relapse rates.
      RESULTS: A total of 210 patients were included, 70 in each arm. On a per-protocol
      basis, there was no difference in pain relapse rates during refeeding between the
      3 diet arms (P=0.80). Subjects initiated on a full solid diet consumed
      significantly more calories and fats on trial days 1 and 2 (P<0.001). A shorter
      LOH (median of -1.5 d) was observed among patients receiving a full solid diet
      without abdominal pain relapse (P=0.000). CONCLUSIONS: Oral refeeding with a full
      solid diet in mild AP was well tolerated and resulted in a shorter LOH in
      patients without abdominal pain relapse.

PMID- 20054283
TI  - Response rates to medical treatments and long-term clinical outcomes of
      nonsurgical patients with intestinal Behcet disease.
AB  - BACKGROUND: The aims of this study were to evaluate the efficacy of medical
      treatments and to identify factors to predict clinical outcome of intestinal
      Behcet disease (BD) during medical treatment. METHODS: We performed a
      retrospective review of the medical records of 93 patients who were diagnosed and
      medically treated with intestinal BD at Severance Hospital, Seoul, Korea from
      1992 to 2007. A therapeutic response was evaluated 8 weeks after the initiation
      of medical treatment, and cumulative recurrence and surgery rates were also
      assessed during long-term follow-up. RESULTS: The initial remission rate at 8
      weeks after treatment was 66.7%. During the follow-up period, cumulative
      recurrence rates for intestinal BD were 24.9% at 2 years and 43.0% at 5 years.
      The recurrence rate was significantly higher in patients with apparent
      gastrointestinal symptoms at their initial presentation, volcano-type and deep
      intestinal ulcers, and those who failed to achieve complete remission during the
      initial treatment. Cumulative rates for surgery were 6.7% at 2 years and 15.1% at
      5 years. The typical type of ulcers was the only predictive factor for the
      likelihood of surgery. CONCLUSIONS: Our study demonstrates that a considerable
      number of patients experience disease relapse during follow-up despite a high
      remission rate after medical treatment for intestinal BD. Careful observation and
      intensive treatment should be carried out, especially in patients without
      complete remission after initial treatment, with deep and volcano-shaped ulcers,
      or with apparent gastrointestinal symptoms at the time of diagnosis.

PMID- 20054284
TI  - Development of Crohn's disease in patients with intestinal failure: a role for
      bacteria?
AB  - We present 3 cases of Crohn's disease that developed in patients with previously
      diagnosed short bowel syndrome from another cause. There are characteristics
      unique to patients with short bowel syndrome that may increase their likelihood
      to develop Crohn's disease, based on current concepts of the pathophysiology of
      inflammatory bowel disease. These patients may have a higher than average
      prevalence of small intestinal bacterial overgrowth. This may lead to an increase
      in bacterial translocation and dysregulation of the intestinal immune response.
      In addition, these patients often require parenteral nutrition (PN) because of
      macronutrient and micronutrient deficiencies. Some patients receiving PN,
      particularly those with bowel obstructions, may be at risk for septicemia due to
      bacterial translocation. It is thought that PN may enhance intestinal dysmotility
      and impair gut immunity, contributing further to an antigenic immune response in
      the intestinal immune system, although supporting data is lacking. Finally,
      studies have demonstrated that patient's with Crohn's disease have a shorter
      bowel length before any intestinal resections and not related to disease
      activity. Although the significance of this is unclear, a shorter bowel length
      may potentially predispose people to the development of Crohn's disease via an
      alteration of intestinal motility and intestinal flora.

PMID- 20054285
TI  - Sequential therapy for Helicobacter pylori eradication: a critical review.
AB  - BACKGROUND: Alternative treatment regimens for standard triple therapy are
      urgently needed. AIM: To critically review the evidence on the role of
      "sequential" regimen for the treatment of Helicobacter pylori infection. METHODS:
      Bibliographical searches were performed in MEDLINE and international congresses.
      RESULTS: Several pooled-data analyses and meta-analyses have demonstrated that
      sequential regimen is more effective than standard triple therapy. Sequential
      therapy is not affected by bacterial (CagA status, infection density) and host
      factors (underlying disease, smoking). Clarithromycin resistance seems to be the
      only factor reducing their efficacy. However, even in these patients, an
      acceptable >75% eradication rate can be achieved. Unfortunately, almost all the
      studies have been performed in Italy. Whether it is necessary to provide the
      drugs sequentially or if the 4 components of sequential therapy can be given
      concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective
      and safe alternative to triple therapy and is less complex than sequential
      therapy. CONCLUSIONS: Sequential therapy is a novel promising treatment approach
      that deserves consideration as a treatment strategy for H. pylori infection.
      However, further robust assessment across a much broader range of patients is
      required before sequential therapy could supplant existing treatment regimens and
      be generally recommended in clinical practice.

PMID- 20054286
TI  - The prevalence of metabolic syndrome in Chinese postmenopausal women and the
      optimum body composition indices to predict it.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of metabolic
      syndrome (MetS) in Chinese postmenopausal women and explore the optimum body
      composition indices to predict MetS. METHODS: Participants were independent,
      community-dwelling women. Recruitment occurred through advertisements in
      newspapers and flyers posted in the local community. A total of 181
      postmenopausal women were recruited. Their parameters were measured, including
      body height, weight, waist circumference (WC), hip circumference, sagittal
      abdominal diameter, blood pressure, follicle-stimulating hormone, luteinizing
      hormone, estradiol, triglyceride, high-density lipoprotein cholesterol, fasting
      plasma glucose, and body fat (BF; %). Logistic regression analyses were applied
      for correlation between stated variables. Optimization of body composition
      indices to predict MetS in postmenopausal women was analyzed with the area under
      the curve of the receiver. RESULTS: The prevalence of MetS in postmenopausal
      women was 33.7%. The risk factors of MetS in postmenopausal women were age,
      family history of metabolic disorders (obesity, hypertension, hyperlipemia, and
      diabetes mellitus), body composition indices (body mass index [BMI], WC, waist-to
      hip ratio, sagittal abdominal diameter, and BF), and metabolic indices (systolic
      and diastolic blood pressure, fasting plasma glucose, and triglyceride; odds
      ratio > 1, P < 0.05), and the protective factor is high-density lipoprotein
      cholesterol (odds ratio = 0.114, P < 0.05). All body composition indices in our
      study had a positive correlation with number of MetS factors. The body
      composition indices in our study showed a positive correlation with each other (P
      < 0.001). BMI and WC were highly correlated with BF (r > 0.900, P < 0.001).
      Through receiver operating characteristic curve analysis, it was determined that
      body composition indices (WC, 80.75 cm; BF, 36.695%; sagittal abdominal diameter,
      18.35 cm; or BMI, 24.835 kg/m) could be used to predict MetS. CONCLUSIONS: The
      prevalence of MetS in Chinese postmenopausal women is 33.7%. Body composition
      indices (WC > or = 80.75 cm, BF > or = 36.695%, sagittal abdominal diameter > or
      = 18.35 cm, or BMI > or = 24.835 kg/m) were discovered to predict MetS.

PMID- 20054287
TI  - The effect of human immunodeficiency virus and breastfeeding on the nutritional
      status of African children.
AB  - BACKGROUND: The risk of HIV-1 infection is high among breast-fed children in sub
      Saharan Africa. Monitoring the nutritional status can provide useful information
      to determine the effect of HIV infection and breast-feeding on child growth and
      development. We longitudinally assessed the nutritional status and determined its
      association with HIV infection and breast-feeding among Malawian children.
      METHODS: We analyzed data from 2 clinical trials to prevent mother-to-child
      transmission of HIV in Malawi. These trials were conducted during 2000-2003
      before the current guidelines were implemented to breast-feed exclusively during
      the first 6 months and wean thereafter. The nutritional status of children was
      measured up to age 24 months, using z-scores. Age-specific differences in length
      for-age (L/A), weight-for-age (W/A), and weight-for-length (W/L) were compared
      stratifying by gender and HIV infection status. Multivariable models examined the
      mean change in z-scores controlling for breast-feeding and other factors.
      RESULTS: In this analysis, 1589 children were included. Boys had significantly
      lower L/A scores and became stunted (z-score -<2 standard deviations) earlier
      than girls. HIV-infected children had significantly lower mean L/A and W/A z
      scores than HIV-uninfected children and became stunted and underweight at an
      earlier age. In multivariable analysis not being breast-fed and being HIV
      infected were significantly (P < 0.001) associated with decreases in mean L/A,
      W/A, and W/L z-scores. CONCLUSIONS: This study shows the impact of infant HIV
      infection on growth and supports the critical importance of breast-feeding.
      Mother-to-child transmission of HIV programs should endeavor to preserve breast
      feeding and find alternative measures to prevent postnatal HIV transmission.

PMID- 20054288
TI  - Efficacy of home-based exercise programmes for people with chronic heart failure:
      a meta-analysis.
AB  - Home-based programmes may offer an alternative to conventional programmes or as a
      means of maintaining physical fitness after graduating from centre-based
      programmes. We sought to examine the effectiveness of home-based exercise
      programmes on exercise capacity in patients with heart failure compared with
      usual medical care. Electronic databases were searched to identify randomized
      controlled trials. Protocols included an initial period of centre-based exercise
      followed by exercise at home, home-based exercise only and concurrent centre and
      home-based exercise. Outcome measures included peak oxygen consumption, exercise
      duration and the six-minute walk test. Nineteen relevant studies were identified
      for review. The mean improvement in peak oxygen consumption was 2.86 ml/kg per
      min [95% confidence interval (CI): 1.43-4.29]. Exercise duration increased by
      1.94 min (95% CI: 0.89-2.98) and distance on the six-minute walk test was
      increased by 30.41 m (95% CI: 6.13-54.68). Other reported benefits of home-based
      programmes include increased quality of life and lowered hospital admission
      rates. In conclusion, home-based exercise programmes have been shown to benefit
      people with heart failure in the short term. Further research is required to
      investigate the long-term effects of home exercise and to determine the optimal
      strategies for improving exercise adherence in patients with heart failure.

PMID- 20054289
TI  - SCORE should be preferred to Framingham to predict cardiovascular death in French
      population.
AB  - BACKGROUND: Numerous studies have examined the validity of available scores to
      predict the absolute cardiovascular risk. DESIGN: We developed a virtual
      population based on data representative of the French population and compared the
      performances of the two most popular risk equations to predict cardiovascular
      death: Framingham and SCORE. METHODS: A population was built based on official
      French demographic statistics and summarized data from representative
      observational studies. The 10-year coronary and cardiovascular death risk and
      their ratio were computed for each individual by SCORE and Framingham equations.
      The resulting rates were compared with those derived from national vital
      statistics. RESULTS: Framingham overestimated French coronary deaths by 2.8 in
      men and 1.9 in women, and cardiovascular deaths by 1.5 in men and 1.3 in women.
      SCORE overestimated coronary death by 1.6 in men and 1.7 in women, and
      underestimated cardiovascular death by 0.94 in men and 0.85 in women. Our results
      revealed an exaggerated representation of coronary among cardiovascular death
      predicted by Framingham, with coronary death exceeding cardiovascular death in
      some individual profiles. Sensitivity analyses gave some insights to explain the
      internal inconsistency of the Framingham equations. CONCLUSION: Evidence is that
      SCORE should be preferred to Framingham to predict cardiovascular death risk in
      French population. This discrepancy between prediction scores is likely to be
      observed in other populations. To improve the validation of risk equations,
      specific guidelines should be issued to harmonize the outcomes definition across
      epidemiologic studies. Prediction models should be calibrated for risk
      differences in the space and time dimensions.

PMID- 20054290
TI  - Fabrication and operation of an oxygen insert for adherent cellular cultures.
AB  - Oxygen is a key modulator of many cellular pathways, but current devices
      permitting in vitro oxygen modulation fail to meet the needs of biomedical
      research. The hypoxic chamber offers a simple system to control oxygenation in
      standard culture vessels, but lacks precise temporal and spatial control over the
      oxygen concentration at the cell surface, preventing its application in studying
      a variety of physiological phenomena. Other systems have improved upon the
      hypoxic chamber, but require specialized knowledge and equipment for their
      operation, making them intimidating for the average researcher. A microfabricated
      insert for multiwell plates has been developed to more effectively control the
      temporal and spatial oxygen concentration to better model physiological phenomena
      found in vivo. The platform consists of a polydimethylsiloxane insert that nests
      into a standard multiwell plate and serves as a passive microfluidic gas network
      with a gas-permeable membrane aimed to modulate oxygen delivery to adherent
      cells. The device is simple to use and is connected to gas cylinders that provide
      the pressure to introduce the desired oxygen concentration into the platform.
      Fabrication involves a combination of standard SU-8 photolithography, replica
      molding, and defined PDMS spinning on a silicon wafer. The components of the
      device are bonded after surface treatment using a hand-held plasma system.
      Validation is accomplished with a planar fluorescent oxygen sensor. Equilibration
      time is on the order of minutes and a wide variety of oxygen profiles can be
      attained based on the device design, such as the cyclic profile achieved in this
      study, and even oxygen gradients to mimic those found in vivo. The device can be
      sterilized for cell culture using common methods without loss of function. The
      device's applicability to studying the in vitro wound healing response will be
      demonstrated.

PMID- 20054291
TI  - Atrial fibrillation in hemodialysis patients: clinical features and associations
      with anticoagulant therapy.
AB  - Using data from the international Dialysis Outcomes and Practice Patterns Study
      (DOPPS), we determined incidence, prevalence, and outcomes among hemodialysis
      patients with atrial fibrillation. Cox proportional hazards models, to identify
      associations with newly diagnosed atrial fibrillation and clinical outcomes, were
      stratified by country and study phase and adjusted for descriptive
      characteristics and comorbidities. Of 17,513 randomly sampled patients, 2188 had
      preexisting atrial fibrillation, with wide variation in prevalence across
      countries. Advanced age, non-black race, higher facility mean dialysate calcium,
      prosthetic heart valves, and valvular heart disease were associated with higher
      risk of new atrial fibrillation. Atrial fibrillation at study enrollment was
      positively associated with all-cause mortality and stroke. The CHADS2 score
      identified approximately equal-size groups of hemodialysis patients with atrial
      fibrillation with low (less than 2) and higher risk (more than 4) for subsequent
      strokes on a per 100 patient-year basis. Among patients with atrial fibrillation,
      warfarin use was associated with a significantly higher stroke risk, particularly
      in those over 75 years of age. Our study shows that atrial fibrillation is common
      and associated with elevated risk of adverse clinical outcomes, and this risk is
      even higher among elderly patients prescribed warfarin. The effectiveness and
      safety of warfarin in hemodialysis patients require additional investigation.

PMID- 20054292
TI  - Endothelial cells as vascular salt sensors.
AB  - Dietary sodium and potassium contribute to the control of the blood pressure.
      Endothelial cells are targets for aldosterone, which activates the apically
      located epithelial sodium channels. The activity of these channels is negatively
      correlated with the release of nitric oxide (NO) and determines endothelial
      function. A mediating factor between channel activity and NO release is the
      mechanical stiffness of the cell's plasma membrane, including the submembranous
      actin network (the cell's 'shell'). Changes in plasma sodium and potassium,
      within the physiological range, regulate the viscosity of this shell and thus
      control the shear-stress-dependent activity of the endothelial NO synthase
      located in the shell's 'pockets' (caveolae). High plasma sodium gelates the shell
      of the endothelial cell, whereas the shell is fluidized by high potassium.
      Accordingly, this concept envisages that communications between extracellular
      ions and intracellular enzymes occur at the plasma membrane barrier, whereas 90%
      of the total cell mass remains uninvolved in these changes. Endothelial cells are
      highly sensitive to extracellular sodium and potassium. This sensitivity may
      serve as a physiological feedback mechanism to regulate local blood flow. It may
      also have pathophysiological relevance when sodium/potassium homeostasis is
      disturbed.

PMID- 20054293
TI  - Fcgamma-receptor IIa polymorphism and the role of immunoadsorption in cardiac
      dysfunction in patients with dilated cardiomyopathy.
AB  - In patients with dilated cardiomyopathy (DCM), cardiac autoantibodies are able to
      bind with their Fab fragment to epitopes on cardiomyocytes, but thereafter they
      crosslink through their Fc fragment to cardiac Fc(gamma)-receptor IIa.
      Polymorphic variability of the Fc(gamma)-receptor IIa is associated with modified
      affinity of immunoglobin G (IgG) binding and may influence therapeutic effects.
      In this study, 103 consecutive DCM patients were treated with immunoadsorption
      (IA) therapy with subsequent IgG substitution (IA/IgG). Echocardiography was
      performed at baseline and again at 3 and 6 months after IA/IgG. Fc(gamma)
      receptor IIa polymorphism R/H131 was genotyped using a nested sequence-specific
      primer polymerase chain reaction (PCR). Patients with the Fc(gamma)-receptor IIa
      genotype R/R131 showed significantly greater improvement in left ventricular (LV)
      function than patients with the R/H131 or H/H131 genotypes did. Irrespective of
      the Fc(gamma)-receptor polymorphism, patients with shorter disease duration and a
      more impaired LV function responded with a greater increase in LV ejection
      fraction (LVEF). Therefore, the Fc(gamma)-receptor polymorphism influences the
      efficacy of immunomodulatory therapy involving IA/IgG.

PMID- 20054294
TI  - KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic
      efficacy of repaglinide in Chinese patients with type 2 diabetes.
AB  - This study showed that the polymorphisms KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T)
      are associated with a heightened risk of developing type 2 diabetes mellitus
      (T2DM). We also explored the effects of these polymorphisms on the efficacy of
      repaglinide therapy in Chinese patients with T2DM. A total of 259 patients with
      T2DM and 188 healthy controls were genotyped. Forty patients with various
      genotypes were randomly selected to undergo an 8-week repaglinide treatment
      regimen. Patients with the G allele of the KCNJ11 Lys23Glu polymorphism showed
      higher levels of fasting plasma glucose (FPG) and postprandial plasma glucose
      (PPG) (P < 0.05). After repaglinide treatment, patients with the GA or AA
      genotype showed higher levels of FPG, PPG, and glycated hemoglobin (HbA(1c))
      compared with patients with the GG genotype (P < 0.05). Patients with the C
      allele of TCF7L2 rs290487(C/T) had higher total cholesterol levels and lower body
      mass index (BMI) (P < 0.05). In patients with the TT genotype, the drug showed
      better efficacy with respect to levels of fasting insulin, triglycerides, and low
      density lipoprotein cholesterol (LDL-c) than in patients with the CC or CT
      genotype (P < 0.05). The KCNJ11 and TCF7L2 polymorphisms were associated with
      repaglinide efficacy.

PMID- 20054295
TI  - Opposing microRNA families regulate self-renewal in mouse embryonic stem cells.
AB  - When embryonic stem cells (ESCs) differentiate, they must both silence the ESC
      self-renewal program and activate new tissue-specific programs. In the absence of
      DGCR8 (Dgcr8(-/-)), a protein required for microRNA (miRNA) biogenesis, mouse
      ESCs are unable to silence self-renewal. Here we show that the introduction of
      let-7 miRNAs-a family of miRNAs highly expressed in somatic cells-can suppress
      self-renewal in Dgcr8(-/-) but not wild-type ESCs. Introduction of ESC cell cycle
      regulating (ESCC) miRNAs into the Dgcr8(-/-) ESCs blocks the capacity of let-7 to
      suppress self-renewal. Profiling and bioinformatic analyses show that let-7
      inhibits whereas ESCC miRNAs indirectly activate numerous self-renewal genes.
      Furthermore, inhibition of the let-7 family promotes de-differentiation of
      somatic cells to induced pluripotent stem cells. Together, these findings show
      how the ESCC and let-7 miRNAs act through common pathways to alternatively
      stabilize the self-renewing versus differentiated cell fates.

PMID- 20054296
TI  - A role for the elongator complex in zygotic paternal genome demethylation.
AB  - The life cycle of mammals begins when a sperm enters an egg. Immediately after
      fertilization, both the maternal and paternal genomes undergo dramatic
      reprogramming to prepare for the transition from germ cell to somatic cell
      transcription programs. One of the molecular events that takes place during this
      transition is the demethylation of the paternal genome. Despite extensive
      efforts, the factors responsible for paternal DNA demethylation have not been
      identified. To search for such factors, we developed a live cell imaging system
      that allows us to monitor the paternal DNA methylation state in zygotes. Through
      short-interfering-RNA-mediated knockdown in mouse zygotes, we identified Elp3
      (also called KAT9), a component of the elongator complex, to be important for
      paternal DNA demethylation. We demonstrate that knockdown of Elp3 impairs
      paternal DNA demethylation as indicated by reporter binding, immunostaining and
      bisulphite sequencing. Similar results were also obtained when other elongator
      components, Elp1 and Elp4, were knocked down. Importantly, injection of messenger
      RNA encoding the Elp3 radical SAM domain mutant, but not the HAT domain mutant,
      into MII oocytes before fertilization also impaired paternal DNA demethylation,
      indicating that the SAM radical domain is involved in the demethylation process.
      Our study not only establishes a critical role for the elongator complex in
      zygotic paternal genome demethylation, but also indicates that the demethylation
      process may be mediated through a reaction that requires an intact radical SAM
      domain.

PMID- 20054301
TI  - Recognizing challenges, expanding horizons: doing what is required.

PMID- 20054297
TI  - Systematic sequencing of renal carcinoma reveals inactivation of histone
      modifying genes.
AB  - Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney
      cancer, characterized by the presence of inactivating mutations in the VHL gene
      in most cases, and by infrequent somatic mutations in known cancer genes. To
      determine further the genetics of ccRCC, we have sequenced 101 cases through
      3,544 protein-coding genes. Here we report the identification of inactivating
      mutations in two genes encoding enzymes involved in histone modification-SETD2, a
      histone H3 lysine 36 methyltransferase, and JARID1C (also known as KDM5C), a
      histone H3 lysine 4 demethylase-as well as mutations in the histone H3 lysine 27
      demethylase, UTX (KMD6A), that we recently reported. The results highlight the
      role of mutations in components of the chromatin modification machinery in human
      cancer. Furthermore, NF2 mutations were found in non-VHL mutated ccRCC, and
      several other probable cancer genes were identified. These results indicate that
      substantial genetic heterogeneity exists in a cancer type dominated by mutations
      in a single gene, and that systematic screens will be key to fully determining
      the somatic genetic architecture of cancer.

PMID- 20054306
TI  - Editorial: Upper GI bleeding-associated mortality: challenges to improving a
      resistant outcome.
AB  - Although the incidence of peptic ulcer bleeding (PUB) has decreased, mortality
      has remained constant despite the advances in endoscopic and pharmacological
      therapies. Recent data indicate that most PUB-linked deaths are not direct
      sequelae of the bleeding ulcer itself. Instead, mortality derives from multi
      organ failure, cardiopulmonary conditions, or terminal malignancy, suggesting
      that improving treatments for the bleeding ulcer may impact mortality by very
      little. Recognizing this possibility is paramount for the implementation of
      strategies that provide supportive care and prevent complications and key-organ
      failure, as well as treat the ulcer. Identifying non-gastrointestinal (GI) risk
      factors for poor outcomes and a multidisciplinary approach for high-risk patients
      should help to affect this hard outcome.

PMID- 20054307
TI  - Editorial: Clostridium difficile infection: Yet another predictor of poor outcome
      in cirrhosis.
AB  - The development of Clostridium difficile infection in cirrhosis is predictive of
      death, independent of severity of liver disease. The main risk factors are the
      use of antibiotics and proton-pump inhibitors (PPIs). This is further evidence
      that supports the wise and cautious use of antibiotics in cirrhosis and suggests
      avoiding the use of PPIs in these patients except for indications of proven
      benefit.

PMID- 20054309
TI  - Use of infliximab in pregnancy.

PMID- 20054310
TI  - Melatonin rhythms in patients with cirrhosis.

PMID- 20054311
TI  - Is gluten sensitivity a "No Man's Land" or a "Fertile Crescent" for research?

PMID- 20054315
TI  - Alanine aminotransferase, metabolic syndrome, and cardiovascular disease: a
      missing link?

PMID- 20054316
TI  - Acid exposure within the dilated end-stage esophagus.

PMID- 20054319
TI  - The serological profile of the autoimmune hepatitis/primary biliary cirrhosis
      overlap syndrome.

PMID- 20054320
TI  - "Blessed are those who have not seen and yet have believed".

PMID- 20054321
TI  - What do most doctors win in a medical malpractice lawsuit?

PMID- 20054322
TI  - Proctocolitis caused by coffee enemas.

PMID- 20054323
TI  - Recanalization of obstructed choledochojejunostomy using the magnet compression
      anastomosis technique.

PMID- 20054324
TI  - A case of hidradenitis suppurativa refractory to anti-TNFalpha therapy in a
      patient with Crohn's disease.

PMID- 20054325
TI  - Pyogenic liver abscess associated with a gastrointestinal stromal tumor of the
      stomach.

PMID- 20054326
TI  - A case report of nephrotic syndrome due to intake of certolizumab pegol in a
      patient with Crohn's disease.

PMID- 20054327
TI  - Balloon enteroscopy for diagnosis and treatment of cytomegalovirus-induced small
      bowel gastrointestinal bleeding after whole-organ pancreas transplantation.

PMID- 20054328
TI  - Lymphocytic myopericarditis in a patient with previously undiagnosed Crohn's
      disease.

PMID- 20054329
TI  - Broken pancreas, broken heart.

PMID- 20054330
TI  - Mycosis fungoides with involvement of the larynx after liver transplantation in
      an adult.

PMID- 20054331
TI  - Herpes simplex virus meningoencephalitis in a patient with Crohn's disease on
      azathioprine therapy.

PMID- 20054333
TI  - Care of individuals with spinal cord lesion: from an untreated ailment, to
      coherent, comprehensive highly specialised care.

PMID- 20054335
TI  - Does IVIg administration yield improved immune function in very premature
      neonates?
AB  - Intravenous immunoglobulin (IVIg) has been evaluated as an adjunctive therapy for
      neonatal sepsis with modest clinical success despite strong biological
      plausibility. Multiple factors contribute to this outcome, but perhaps none
      greater than the limited immune system function in newborns, especially in the
      very premature neonates. For very premature neonates (<30 weeks gestational age),
      understanding the effects of IVIg on specific immature immune system functions is
      particularly relevant given their preponderance to develop sepsis and therefore
      potentially benefit from IVIg-mediated immunoenhancement. Here, we review the
      available evidence for enhanced immune function after IVIg administration in very
      premature neonates and highlight areas for future research.

PMID- 20054336
TI  - Reference ranges for blood concentrations of eosinophils and monocytes during the
      neonatal period defined from over 63 000 records in a multihospital health-care
      system.
AB  - OBJECTIVE: Blood concentrations of eosinophils and monocytes are part of the
      complete blood count. Reference ranges for these concentrations during the
      neonatal period, established by very large sample sizes and modern methods, are
      needed for identifying abnormally low or high values. STUDY DESIGN: We
      constructed reference ranges for eosinophils per microl and monocytes per microl
      among neonates of 22 to 42 weeks of gestation, on the day of birth, and also
      during 28 days after birth. Data were obtained from archived electronic records
      over an eight and one-half-year period in a multihospital health-care system. In
      keeping with the reference range concept, values were excluded from neonates with
      a diagnosis of infection or necrotizing enterocolitis (NEC). RESULT: Eosinophils
      and monocytes per microl of blood were electronically retrieved from 96 162
      records, of which 63 371 that lacked a diagnosis of infection or NEC were
      included in this reference range report. The mean value for eosinophils per
      microl on the day of birth increased linearly between 22 and 42 weeks of
      gestation, as did the 5 and 95% values. The reference range at 40 weeks was 140
      to 1300 microl(-1) (mean 550 microl(-1)). Similarly, the mean value for monocytes
      increased linearly over this interval, with a reference range at 40 weeks of 300
      to 3300 microl(-1) (mean 1400 microl(-1)). Over the first 4 weeks after birth, no
      appreciable change was observed in 5% limit and mean eosinophil count, with a
      slight increase in the 95% limit in week 4. A slight increase in monocyte count
      was observed during the first 2 weeks after birth. CONCLUSION: The results of
      this analysis describe reference ranges for blood concentrations of eosinophils
      and monocytes during the neonatal period. Additional study is needed for
      determining the relevance of values falling outside the reference range.

PMID- 20054337
TI  - Lipid rafts and the oxidative stress hypothesis.

PMID- 20054338
TI  - Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in
      keratinocytes.
AB  - Psoriasis is an inflammatory skin disorder with aberrant regulation of
      keratinocytes and immunocytes. Although it is well known that uncontrolled
      keratinocyte proliferation is largely driven by proinflammatory cytokines from
      the immunocytes, the functional role of keratinocytes in the regulation of
      immunocytes is poorly understood. Recently, we found that tripartite motif
      containing protein 32 (Trim32), an E3-ubiquitin ligase, is elevated in the
      epidermal lesions of human psoriasis. We previously showed that Trim32 binds to
      the protein inhibitor of activated STAT-Y (Piasy) and mediates its degradation
      through ubiquitination. Interestingly, the Piasy gene is localized in the PSORS6
      susceptibility locus on chromosome 19p13, and Piasy negatively regulates the
      activities of several transcription factors, including NF-kappaB, STAT, and
      SMADs, that are implicated in the pathogenesis of psoriasis. In this study, we
      show that Trim32 activates, and Piasy inhibits, keratinocyte production of CC
      chemokine ligand 20 (CCL20), a psoriatic chemokine essential for recruitment of
      DCs and T helper (Th)17 cells to the skin. Further, Trim32/Piasy regulation of
      CCL20 is mediated through Piasy interaction with the RelA/p65 subunit of NF
      kappaB. As CCL20 is activated by Th17 cytokines, the upregulation of CCL20
      production by Trim32 provides a positive feedback loop of CCL20 and Th17
      activation in the self-perpetuating cycle of psoriasis.

PMID- 20054339
TI  - Tannic acid and quercetin display a therapeutic effect in atopic dermatitis via
      suppression of angiogenesis and TARC expression in Nc/Nga mice.

PMID- 20054340
TI  - Inhibition of Akt signaling by exclusion from lipid rafts in normal and
      transformed epidermal keratinocytes.
AB  - Lipid rafts are cholesterol-rich plasma membrane domains that regulate signal
      transduction. Because our earlier work indicated that raft disruption inhibited
      proliferation and caused cell death, we investigated here the role of membrane
      cholesterol, the crucial raft constituent, in the regulation of the
      phosphatidylinositol-3 kinase (PI3K)/Akt pathway. Raft disruption was achieved in
      normal human keratinocytes and precancerous (HaCaT) or transformed (A431)
      keratinocytes by cholesterol extraction or inactivation with methyl-beta
      cyclodextrin, filipin III, or 5-cholestene-5-beta-ol. Lipid raft disruption did
      not affect PI3K binding to its main target, the epidermal growth factor receptor,
      nor its ability to convert phosphatidylinositol 4,5-bisphosphate to
      phosphatidylinositol 3,4,5-trisphosphate but impaired Akt phosphorylation at the
      regulatory sites Thr(308) and Ser(473). Diminished Akt activity resulted in
      deactivation of mammalian target of rapamycin, activation of FoxO3a, and
      increased sensitivity to apoptosis stimuli. Lipid raft disruption abrogated the
      binding of Akt and the major Akt kinase, phosphatidylinositol-dependent kinase 1,
      to the membrane by pleckstrin-homology domains. Thus, the integrity of lipid
      rafts is required for the activity of Akt and cell survival and may serve as a
      potential pharmacological target in the treatment of epidermal cancers.

PMID- 20054341
TI  - IRF4 expression without IRF4 rearrangement is a general feature of primary
      cutaneous diffuse large B-cell lymphoma, leg type.

PMID- 20054342
TI  - A prevalent mutation with founder effect in xeroderma pigmentosum group C from
      north Africa.
AB  - Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder that is
      associated with an inherited defect of the nucleotide excision repair pathway
      (NER). In this study, we investigated the involvement of XP genes in 86 XP
      patients belonging to 66 unrelated families, most of them consanguineous and
      originating from Maghreb. Sequencing analysis was performed either directly (44
      probands) or after having previously characterized the involved XP gene by
      complementation assay (22 families). XPC and XPA mutations were respectively
      present in 56/66 and 8/66 probands. Strikingly, we identified the same homozygous
      frameshift mutation c.1643_1644delTG (p.Val548AlafsX25) in 87% of XP-C patients.
      Haplotype analysis showed a common founder effect for this mutation in the
      Mediterranean region, with an estimated age of 50 generations or 1,250 years.
      Among 7/8 XP-A patients, we found the previously reported nonsense homozygous XPA
      mutation (p.Arg228X). Six mutations--to our knowledge previously unreported-
      (five in XPC, one in XPA) were also identified. In conclusion, XPC appears to be
      the major disease-causing gene concerning xeroderma pigmentosum in North Africa.
      As the (p.Val548AlafsX25) XPC mutation is responsible for a huge proportion of XP
      cases, our data imply an obvious simplification of XP molecular diagnosis, at
      least in North Africa.

PMID- 20054343
TI  - Genetic variation within the HLA class III influences T1D susceptibility
      conferred by high-risk HLA haplotypes.
AB  - Human leukocyte antigen (HLA) class II DRB1 and DQB1 represent the major type I
      diabetes (T1D) genetic susceptibility loci; however, other genes in the HLA
      region are also involved in T1D risk. We analyzed 1411 pedigrees (2865 affected
      individuals) from the type I diabetes genetics consortium genotyped for HLA
      classical loci and for 12 single-nucleotide polymorphisms (SNPs) in the class III
      region previously shown to be associated with T1D in a subset of 886 pedigrees.
      Using the transmission disequilibrium test, we compared the proportion of SNP
      alleles transmitted from within the high-risk DR3 and DR4 haplotypes to affected
      offspring. Markers rs4151659 (mapping to CFB) and rs7762619 (mapping 5' of LTA)
      were the most strongly associated with T1D on DR3 (P=1.2 x 10(-9) and P=2 x 10(
      12), respectively) and DR4 (P=4 x 10(-15) and P=8 x 10(-8), respectively)
      haplotypes. They remained significantly associated after stratifying individuals
      in analyses for B*1801, A*0101-B*0801, DPB1*0301, DPB1*0202, DPB1*0401 or
      DPB1*0402. Rs7762619 and rs4151659 are in strong linkage disequilibrium (LD)
      (r(2)=0.82) with each other, but a joint analysis showed that the association for
      each SNP was not solely because of LD. Our data support a role for more than one
      locus in the class III region contributing to risk of T1D.

PMID- 20054345
TI  - Out with gout: opening the door on acute inflammation.

PMID- 20054344
TI  - Insulin gene VNTR genotype associates with frequency and phenotype of the
      autoimmune response to proinsulin.
AB  - Immune responses to autoantigens are in part controlled by deletion of
      autoreactive cells through genetically regulated selection mechanisms. We have
      directly analyzed peripheral CD4+ proinsulin (PI) 76-90 (SLQPLALEGSLQKRG)
      specific T cells using soluble fluorescent major histocompatibility complex class
      II tetramers. Subjects with type I diabetes and healthy controls with high levels
      of peripheral proinsulin-specific T cells were characterized by the presence of a
      disease-susceptible polymorphism in the insulin variable number of tandem repeats
      (INS-VNTR) gene. Conversely, subjects with a 'protective' polymorphism in the INS
      VNTR gene had nearly undetectable levels of proinsulin tetramer-positive T cells.
      These results strongly imply a direct relationship between genetic control of
      autoantigen expression and peripheral autoreactivity, in which proinsulin
      genotype restricts the quantity and quality of the potential T-cell response.
      Using a modified tetramer to isolate low-avidity proinsulin-specific T cells from
      subjects with the susceptible genotype, transcript arrays identified several
      induced pro-apoptotic genes in the control, but not diabetic subjects, likely
      representing a second peripheral mechanism for maintenance of tolerance to self
      antigens.

PMID- 20054346
TI  - The effect of blood pressure and cholesterol variability on the precision of
      Framingham cardiovascular risk estimation: a simulation study.
AB  - This simulation study investigates the effects of within-individual variability
      in estimated cardiovascular risk on categorization of patients as high risk.
      Published estimates of within-individual blood pressure and cholesterol
      variability were used to generate blood pressure and cholesterol levels for
      hypothetical subjects at a range of ages. These were used to calculate the
      estimated cardiovascular risk of each individual. The relationship between an
      individual's mean cardiovascular risk and within-individual coefficient of
      variation for cardiovascular risk was determined. Using the derived relationship,
      mean cardiovascular risk and within-individual variation in risk was calculated
      for 5018 adults from a population health survey. From this, was determined their
      probability of being classified as high risk (>20% 10-year cardiovascular risk)
      and the test characteristics of risk estimation at a range of ages. Within
      individual variability in cardiovascular risk and potential for misclassification
      are both greater in lower-risk populations. At age 35-44 years, the positive
      predictive value of a diagnosis of high risk is 0.61 (95% confidence interval
      (CI): 0.59-0.64), and at age 65-74 years, it is 0.94 (95% CI: 0.91-0.96). About
      39% of adults under 45 years diagnosed as high risk are not at high risk.
      Cardiovascular risk assessment should be targeted at high-risk populations.

PMID- 20054347
TI  - Blood pressure status and post-exercise hypotension: an example of a spurious
      correlation in hypertension research?
AB  - A single bout of exercise lowers blood pressure (BP) for up to 24 h afterwards.
      The magnitude of this post-exercise hypotension (PEH) has been reported to be
      correlated most strongly to pre-exercise BP, and this apparent relationship has
      influenced position statements about the value of exercise in arterial
      hypertension. Nevertheless, this correlation could be adversely affected by
      mathematical coupling and regression-to-the-mean artefacts. Therefore, we aimed
      to examine the degree to which BP status moderates PEH while, for the first time,
      controlling for these statistical artefacts. A total of 32 participants, with pre
      exercise mean arterial pressures of 65-110 mm Hg, cycled for 30 min at 70% peak
      oxygen uptake. Systolic BP and diastolic BP were measured (Portapres) before
      exercise and for 20 min after exercise. Changes in BP were regressed against pre
      exercise values, and against the mean of pre- and post-exercise BP, among other
      indices that are also known not to be prone to artefacts. Correlations between
      pre-exercise BP and the exercise-mediated reductions were typical of those
      previously reported (r=0.37-0.62, P<0.05), but not large enough to rule out
      spuriousness (P>0.05). Artefact-free indices of BP status (pre- and post-exercise
      mean as well as an earlier independent measurement) did not correlate with
      reductions in BP (P>0.05), which were moderated more by peak oxygen uptake and
      time of day (P<0.05). These data indicate that, if statistical artefacts are not
      controlled for, the influence of BP status on the degree of PEH can be spuriously
      exaggerated to the extent that other more important moderators of BP change are
      masked.

PMID- 20054348
TI  - Total antioxidant status and oxidative DNA damage in a South Indian population of
      essential hypertensives.
AB  - To investigate the total antioxidant status (TAS) and the extent of oxidative DNA
      damage in total lymphocytes and their relation with essential hypertension. A
      total of 130 South Indian subjects aged 30-65 were recruited for the study. Of
      these hypertensive subjects investigated, 30 were newly diagnosed and were not on
      any antihypertensive drugs, but had systolic blood pressure (BP) ranging between
      140 and 160 mm Hg and diastolic BP between 95 and 100 mm Hg; 50 hypertensive
      patients who were already on drug therapy for 1 year and 50 were normotensive
      controls with BP < or =120/80 mm Hg. DNA damage was significantly increased in
      hypertensive patients (both newly diagnosed and who were already on drug therapy)
      compared with control group. The major increase in DNA damage was observed in
      newly diagnosed hypertensive patients compared with hypertensive patients who
      were already on drug therapy. There was a significant decrease in plasma TAS
      value in essential hypertensive groups as compared to normotensive controls.
      Lymphocyte DNA damage was independently correlated with only TAS. Lymphocyte DNA
      damage was increased in hypertensive patients. The major increase in lymphocyte
      DNA damage was observed in newly diagnosed hypertensive patients compared with
      hypertensive patients who already on drug therapy. Decreased TAS levels, which
      reflect to increased oxidative stress, may be the reason of increased total
      lymphocyte DNA damage in South Indian hypertensive patients.

PMID- 20054349
TI  - Switching of antihypertensive drugs among 93,286 Chinese patients: a cohort
      study.
AB  - Antihypertensive drug switching induces substantial public health costs. This
      cohort study evaluated factors associated with switching of antihypertensive
      agents 180 days after the first date of prescription among ethnic Chinese
      patients. We included all adult patients aged > or =18 years, who had paid at
      least two consecutive visits to all public primary care clinics in one large
      territory of Hong Kong during the study period from January 2004 to June 2007.
      Binary logistic regression analyses were carried out with antihypertensive drug
      switching as an outcome variable, while controlling for age, gender, payment
      status, service types, district of residence, visit types and the number of
      comorbidities. Among 93,286 eligible patients, 5281 (5.7%) switched their
      antihypertensive prescriptions to another drug class within 180 days. Patients
      aged > or =70 years (adjusted odds ratio (aOR) 0.88, P=0.005), male subjects (aOR
      0.87, P<0.001) and follow-up visitors (aOR 0.67, P<0.001) were less likely to
      have their drugs switched. When compared with thaizide diuretics, all other
      antihypertensive drug classes were associated with a lower likelihood of drug
      switching (aOR 0.27-0.69, all P<0.001). Closer observations of drug utilization
      profiles among these patient groups are recommended, and future studies should
      evaluate the reasons for drug switching.

PMID- 20054350
TI  - ARID5B SNP rs10821936 is associated with risk of childhood acute lymphoblastic
      leukemia in blacks and contributes to racial differences in leukemia incidence.

PMID- 20054351
TI  - Deregulation of microRNA expression in the different genetic subtypes of multiple
      myeloma and correlation with gene expression profiling.
AB  - Specific microRNA (miRNA) signatures have been associated with different
      cytogenetic subtypes in acute leukemias. This finding prompted us to investigate
      potential associations between genetic abnormalities in multiple myeloma (MM) and
      singular miRNA expression profiles. Moreover, global gene expression profiling
      was also analyzed to find correlated miRNA gene expression and select miRNA
      target genes that show such correlation. For this purpose, we analyzed the
      expression level of 365 miRNAs and the gene expression profiling in 60 newly
      diagnosed MM patients, selected to represent the most relevant recurrent genetic
      abnormalities. Supervised analysis showed significantly deregulated miRNAs in the
      different cytogenetic subtypes as compared with normal PC. It is interesting to
      note that miR-1 and miR-133a clustered on the same chromosomal loci, were
      specifically overexpressed in the cases with t(14;16). The analysis of the
      relationship between miRNA expression and their respective target genes showed a
      conserved inverse correlation between several miRNAs deregulated in MM cells and
      CCND2 expression level. These results illustrate, for the first time, that miRNA
      expression pattern in MM is associated with genetic abnormalities, and that the
      correlation of the expression profile of miRNA and their putative mRNA targets is
      useful to find statistically significant protein-coding genes in MM pathogenesis
      associated with changes in specific miRNAs.

PMID- 20054352
TI  - Failure is not fatal: long-term remission in refractory acute myeloid leukemia
      (AML) after graft failure of cord blood stem cells.

PMID- 20054354
TI  - The battle to prevent the transmission of mitochondrial DNA disease: is
      karyoplast transfer the answer?

PMID- 20054353
TI  - The SP-C promoter facilitates alveolar type II epithelial cell-specific plasmid
      nuclear import and gene expression.
AB  - Although nonviral gene therapy has great potential for use in the lung, the
      relative lack of cell-specific targeting has limited its applications. We have
      developed a new approach for cell-specific targeting based on selective nuclear
      import of plasmids in nondividing cells. Using a microinjection and in situ
      hybridization approach, we tested several potential DNA sequences for the ability
      to mediate plasmid nuclear import in alveolar type II epithelial (ATII) cells. Of
      these, only a sequence within the human surfactant protein C (SP-C) promoter was
      able to mediate nuclear localization of plasmid DNA specifically in ATII cells
      but not in other cell types. We have mapped the minimal import sequence to the
      proximal 318 nucleotides of the promoter, and demonstrate that binding sites for
      nuclear factor I, thyroid transcriptional factor 1, and GATA-binding protein 6
      and the proteins themselves are required for import activity. Using intratracheal
      delivery of DNA followed by electroporation, we demonstrate that the SP-C
      promoter sequence will enhance gene expression specifically in ATII cells in
      mouse lung. This represents a new activity for the SP-C promoter, and thus ATII
      cell-specific nuclear import of DNA may prove to be a safe and effective method
      for targeted and enhanced gene expression in ATII cells.

PMID- 20054355
TI  - Activity profiles for marine sponge-associated bacteria obtained by 16S rRNA vs
      16S rRNA gene comparisons.
AB  - The phylogenetic diversity of microorganisms in marine sponges is becoming
      increasingly well described, yet relatively little is known about the activities
      of these symbionts. Given the seemingly favourable environment provided to
      microbes by their sponge hosts, as indicated by the extraordinarily high
      abundance of sponge symbionts, we hypothesized that the majority of sponge
      associated bacteria are active in situ. To test this hypothesis we compared, for
      the first time in sponges, 16S rRNA gene- vs 16S rRNA-derived bacterial community
      profiles to gain insights into symbiont composition and activity, respectively.
      Clone libraries revealed a highly diverse bacterial community in Ancorina alata,
      and a much lower diversity in Polymastia sp., which were identified by electron
      microscopy as a high- and a low-microbial abundance sponge, respectively.
      Substantial overlap between DNA and RNA libraries was evident at both phylum and
      phylotype levels, indicating in situ activity for a large fraction of sponge
      associated bacteria. This active fraction included uncultivated, sponge-specific
      lineages within, for example, Actinobacteria, Chloroflexi and Gemmatimonadetes.
      This study shows the potential of RNA vs DNA comparisons based on the 16S rRNA
      gene to provide insights into the activity of sponge-associated microorganisms.

PMID- 20054356
TI  - Distinct flavobacterial communities in contrasting water masses of the north
      Atlantic Ocean.
AB  - Members of the class Flavobacteria in the phylum Bacteroidetes are among the most
      abundant picoplankton in coastal and polar oceans. Their diversity is high in
      marine waters. However, quantitative information about distribution patterns of
      flavobacterial clades is scarce. We analyzed the diversity and clade-specific
      abundances of individual Flavobacteria in different oceanic provinces in the
      North Atlantic Ocean. Samples were taken along the 30 degrees W meridian between
      the East Greenland current and the North Atlantic subtropical gyre. Comparative
      sequence analysis of 16S ribosomal RNA (rRNA) gene libraries revealed high
      diversity and significant spatial variability within the class Flavobacteria.
      Published and newly designed oligonucleotide probes were used to enumerate eleven
      flavobacterial clades by catalyzed reporter deposition fluorescence in situ
      hybridization (CARD-FISH). We found that different provinces harbor distinct
      flavobacterial communities. Clade DE2 accounted for a substantial fraction of
      total Flavobacteria only in the Polar Biome (BPLR), whereas the VISION clades
      VIS1 and VIS4 significantly increased in the Arctic (ARCT) province. Members of
      the genus Polaribacter were the most abundant clade in all the water masses
      analyzed, with highest absolute numbers in BPLR and ARCT. We improved the CARD
      FISH protocol to quantify the rare clades VIS2, VIS3, VIS5 and VIS6, which were
      present in abundances below 0.5%. They all showed pronounced regional
      distribution patterns. Microscopic analysis proved a specific enrichment of
      Flavobacteria in the phycosphere of nanophytoplankton of BPLR and ARCT. Our
      results suggest that different marine flavobacterial clades have distinct niches
      and different life strategies.

PMID- 20054357
TI  - Evolutionary divergence and biogeography of sympatric niche-differentiated
      bacterial populations.
AB  - Using multiple lines of evidence from denaturing gradient gel electrophoresis,
      environmental sequences and TaqMan quantitative PCR assays targeting a functional
      gene for sulfate respiration (dsr) affiliated with the geochemically important
      genus Desulfobulbus, we revealed strongly restricted distributions of specific
      genotypes and populations correlated with sampling position along an estuarine
      gradient free of dispersal barriers. Evidence of evolutionary divergence of
      populations was provided by three complementary analyses. First, analysis of
      molecular variance rejected the null hypothesis that genetic diversity within
      each sampling site was not significantly different than that of all sites pooled
      together (P<0.0001). Second, UniFrac and Parsimony tests showed phylogenetic
      clustering of sampling sites was highly significant (P<0.001). Third, pairwise
      F(ST) statistics showed significant evolutionary divergence of populations based
      on the location in the estuary. To test the hypothesis that environmental niche
      driven evolutionary divergence can create and maintain microbial biogeography, we
      used both statistical inference and an experimental manipulation to assess the
      independent effects of environment and geography. Significant effects of each on
      genotype distributions and population divergence supported the hypothesis. Our
      data are consistent with both sympatric and parapatric models of speciation, and
      suggest niche partitioning can contribute to evolutionary divergence and
      observable biogeographic patterns in microbial communities even among closely
      related taxa at limited spatial scales without significant barriers to dispersal.

PMID- 20054358
TI  - Close supermassive binary black holes.
AB  - It has been proposed that when the peaks of the broad emission lines in active
      galactic nuclei (AGNs) are significantly blueshifted or redshifted from the
      systemic velocity of the host galaxy, this could be a consequence of orbital
      motion of a supermassive black-hole binary (SMBB). The AGN J1536+0441 ( = SDSS
      J153636.22+044127.0) has recently been proposed as an example of this phenomenon.
      It is proposed here instead that J1536+0441 is an example of line emission from a
      disk. If this is correct, the lack of clear optical spectral evidence for close
      SMBBs is significant, and argues either that the merging of close SMBBs is much
      faster than has generally been hitherto thought, or if the approach is slow, that
      when the separation of the binary is comparable to the size of the torus and
      broad-line region, the feeding of the black holes is disrupted.

PMID- 20054363
TI  - A decade for psychiatric disorders.

PMID- 20054365
TI  - Shorter NIH grant form launches.

PMID- 20054366
TI  - New year, new science.

PMID- 20054367
TI  - Israeli government advisers threaten walkout.

PMID- 20054369
TI  - Kepler finds its first planets.

PMID- 20054368
TI  - Chemists crack complex compound.

PMID- 20054370
TI  - Floods linked to San Andreas quakes.

PMID- 20054371
TI  - Institutions investigate 'reactome' data.

PMID- 20054372
TI  - Smart grids: The energy storage problem.

PMID- 20054373
TI  - Ecology: Wish you were here.

PMID- 20054374
TI  - World view: Tomorrow never knows.

PMID- 20054375
TI  - Climate e-mails: lack of data sharing is a real concern.

PMID- 20054376
TI  - Icelandic genetic database not at risk from bankruptcy.

PMID- 20054377
TI  - Step up aspirations to save biodiversity as 2010 begins.

PMID- 20054378
TI  - Climate e-mails: man's mark is clear in thermometer record.

PMID- 20054379
TI  - 2020 visions.

PMID- 20054383
TI  - Supernovae: A smashing success.

PMID- 20054384
TI  - Neuroscience: Editing out fear.

PMID- 20054385
TI  - Quantum physics: Trapped ion set to quiver.

PMID- 20054386
TI  - Virology: Bornavirus enters the genome.

PMID- 20054387
TI  - Palaeontology: Muddy tetrapod origins.

PMID- 20054388
TI  - Tetrapod trackways from the early Middle Devonian period of Poland.
AB  - The fossil record of the earliest tetrapods (vertebrates with limbs rather than
      paired fins) consists of body fossils and trackways. The earliest body fossils of
      tetrapods date to the Late Devonian period (late Frasnian stage) and are preceded
      by transitional elpistostegids such as Panderichthys and Tiktaalik that still
      have paired fins. Claims of tetrapod trackways predating these body fossils have
      remained controversial with regard to both age and the identity of the track
      makers. Here we present well-preserved and securely dated tetrapod tracks from
      Polish marine tidal flat sediments of early Middle Devonian (Eifelian stage) age
      that are approximately 18 million years older than the earliest tetrapod body
      fossils and 10 million years earlier than the oldest elpistostegids. They force a
      radical reassessment of the timing, ecology and environmental setting of the fish
      tetrapod transition, as well as the completeness of the body fossil record.

PMID- 20054390
TI  - Sub-luminous type Ia supernovae from the mergers of equal-mass white dwarfs with
      mass approximately 0.9M[symbol: see text].
AB  - Type Ia supernovae are thought to result from thermonuclear explosions of carbon
      oxygen white dwarf stars. Existing models generally explain the observed
      properties, with the exception of the sub-luminous 1991bg-like supernovae. It has
      long been suspected that the merger of two white dwarfs could give rise to a type
      Ia event, but hitherto simulations have failed to produce an explosion. Here we
      report a simulation of the merger of two equal-mass white dwarfs that leads to a
      sub-luminous explosion, although at the expense of requiring a single common
      envelope phase, and component masses of approximately 0.9M[symbol: see text]. The
      light curve is too broad, but the synthesized spectra, red colour and low
      expansion velocities are all close to what is observed for sub-luminous 1991bg
      like events. Although the mass ratios can be slightly less than one and still
      produce a sub-luminous event, the masses have to be in the range 0.83M[symbol:
      see text] to 0.9M[symbol: see text].

PMID- 20054389
TI  - Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii.
AB  - Archaea, one of three major evolutionary lineages of life, encode proteasomes
      highly related to those of eukaryotes. In contrast, archaeal ubiquitin-like
      proteins are less conserved and not known to function in protein conjugation.
      This has complicated our understanding of the origins of ubiquitination and its
      connection to proteasomes. Here we report two small archaeal modifier proteins,
      SAMP1 and SAMP2, with a beta-grasp fold and carboxy-terminal diglycine motif
      similar to ubiquitin, that form protein conjugates in the archaeon Haloferax
      volcanii. The levels of SAMP-conjugates were altered by nitrogen-limitation and
      proteasomal gene knockout and spanned various functions including components of
      the Urm1 pathway. LC-MS/MS-based collision-induced dissociation demonstrated
      isopeptide bonds between the C-terminal glycine of SAMP2 and the epsilon-amino
      group of lysines from a number of protein targets and Lys 58 of SAMP2 itself,
      revealing poly-SAMP chains. The widespread distribution and diversity of pathways
      modified by SAMPylation suggest that this type of protein conjugation is central
      to the archaeal lineage.

PMID- 20054391
TI  - A lower limit of 50 microgauss for the magnetic field near the Galactic Centre.
AB  - The amplitude of the magnetic field near the Galactic Centre has been uncertain
      by two orders of magnitude for several decades. On a scale of approximately 100
      parsecs (pc), fields of approximately 1,000 microgauss (microG; refs 1-3) have
      been reported, implying a magnetic energy density more than 10,000 times stronger
      than typical for the Galaxy. Alternatively, the assumption of pressure
      equilibrium between the various phases of the Galactic Centre interstellar medium
      (including turbulent molecular gas, the contested 'very hot' plasma, and the
      magnetic field) suggests fields of approximately 100 microG over approximately
      400 pc size scales. Finally, assuming equipartition, fields of only approximately
      6 microG have been inferred from radio observations for 400 pc scales. Here we
      report a compilation of previous data that reveals a downward break in the
      region's non-thermal radio spectrum (attributable to a transition from
      bremsstrahlung to synchrotron cooling of the in situ cosmic-ray electron
      population). We show that the spectral break requires that the Galactic Centre
      field be at least approximately 50 microG on 400 pc scales, lest the synchrotron
      emitting electrons produce too much gamma-ray emission, given other existing
      constraints. Other considerations support a field of 100 microG, implying that
      over 10% of the Galaxy's magnetic energy is contained in only less than or
      approximately 0.05% of its volume.

PMID- 20054392
TI  - Quantum simulation of the Dirac equation.
AB  - The Dirac equation successfully merges quantum mechanics with special relativity.
      It provides a natural description of the electron spin, predicts the existence of
      antimatter and is able to reproduce accurately the spectrum of the hydrogen atom.
      The realm of the Dirac equation-relativistic quantum mechanics-is considered to
      be the natural transition to quantum field theory. However, the Dirac equation
      also predicts some peculiar effects, such as Klein's paradox and
      'Zitterbewegung', an unexpected quivering motion of a free relativistic quantum
      particle. These and other predicted phenomena are key fundamental examples for
      understanding relativistic quantum effects, but are difficult to observe in real
      particles. In recent years, there has been increased interest in simulations of
      relativistic quantum effects using different physical set-ups, in which parameter
      tunability allows access to different physical regimes. Here we perform a proof
      of-principle quantum simulation of the one-dimensional Dirac equation using a
      single trapped ion set to behave as a free relativistic quantum particle. We
      measure the particle position as a function of time and study Zitterbewegung for
      different initial superpositions of positive- and negative-energy spinor states,
      as well as the crossover from relativistic to non-relativistic dynamics. The high
      level of control of trapped-ion experimental parameters makes it possible to
      simulate textbook examples of relativistic quantum physics.

PMID- 20054393
TI  - Slip-stick and the evolution of frictional strength.
AB  - The evolution of frictional strength has great fundamental and practical
      importance. Applications range from earthquake dynamics to hard-drive read/write
      cycles. Frictional strength is governed by the resistance to shear of the large
      ensemble of discrete contacts that forms the interface that separates two sliding
      bodies. An interface's overall strength is determined by both the real contact
      area and the contacts' shear strength. Whereas the average motion of large,
      slowly sliding bodies is well-described by empirical friction laws, interface
      strength is a dynamic entity that is inherently related to both fast processes
      such as detachment/re-attachment and the slow process of contact area
      rejuvenation. Here we show how frictional strength evolves from extremely short
      to long timescales, by continuous measurements of the concurrent local evolution
      of the real contact area and the corresponding interface motion (slip) from the
      first microseconds when contact detachment occurs to large (100-second)
      timescales. We identify four distinct and inter-related phases of evolution.
      First, all of the local contact area reduction occurs within a few microseconds,
      on the passage of a crack-like front. This is followed by the onset of rapid slip
      over a characteristic time, the value of which suggests a fracture-induced
      reduction of contact strength before any slip occurs. This rapid slip phase
      culminates with a sharp transition to slip at velocities an order of magnitude
      slower. At slip arrest, 'ageing' immediately commences as contact area increases
      on a characteristic timescale determined by the system's local memory of its
      effective contact time before slip arrest. We show how the singular logarithmic
      behaviour generally associated with ageing is cut off at short times. These
      results provide a comprehensive picture of how frictional strength evolves from
      the short times and rapid slip velocities at the onset of motion to ageing at the
      long times following slip arrest.

PMID- 20054394
TI  - Anthropogenic carbon dioxide transport in the Southern Ocean driven by Ekman
      flow.
AB  - The Southern Ocean, with its large surface area and vigorous overturning
      circulation, is potentially a substantial sink of anthropogenic CO(2) (refs 1-4).
      Despite its importance, the mechanism and pathways of anthropogenic CO(2) uptake
      and transport are poorly understood. Regulation of the Southern Ocean carbon sink
      by the wind-driven Ekman flow, mesoscale eddies and their interaction is under
      debate. Here we use a high-resolution ocean circulation and carbon cycle model to
      address the mechanisms controlling the Southern Ocean sink of anthropogenic
      CO(2). The focus of our study is on the intra-annual variability in anthropogenic
      CO(2) over a two-year time period. We show that the pattern of carbon uptake is
      correlated with the oceanic vertical exchange. Zonally integrated carbon uptake
      peaks at the Antarctic polar front. The carbon is then advected away from the
      uptake regions by the circulation of the Southern Ocean, which is controlled by
      the interplay among Ekman flow, ocean eddies and subduction of water masses.
      Although lateral carbon fluxes are locally dominated by the imprint of mesoscale
      eddies, the Ekman transport is the primary mechanism for the zonally integrated,
      cross-frontal transport of anthropogenic CO(2). Intra-annual variability of the
      cross-frontal transport is dominated by the Ekman flow with little compensation
      from eddies. A budget analysis in the density coordinate highlights the
      importance of wind-driven transport across the polar front and subduction at the
      subtropical front. Our results suggest intimate connections between oceanic
      carbon uptake and climate variability through the temporal variability of Ekman
      transport.

PMID- 20054395
TI  - Endogenous non-retroviral RNA virus elements in mammalian genomes.
AB  - Retroviruses are the only group of viruses known to have left a fossil record, in
      the form of endogenous proviruses, and approximately 8% of the human genome is
      made up of these elements. Although many other viruses, including non-retroviral
      RNA viruses, are known to generate DNA forms of their own genomes during
      replication, none has been found as DNA in the germline of animals. Bornaviruses,
      a genus of non-segmented, negative-sense RNA virus, are unique among RNA viruses
      in that they establish persistent infection in the cell nucleus. Here we show
      that elements homologous to the nucleoprotein (N) gene of bornavirus exist in the
      genomes of several mammalian species, including humans, non-human primates,
      rodents and elephants. These sequences have been designated endogenous Borna-like
      N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame
      (ORF) and are expressed as mRNA. Phylogenetic analyses showed that EBLNs seem to
      have been generated by different insertional events in each specific animal
      family. Furthermore, the EBLN of a ground squirrel was formed by a recent
      integration event, whereas those in primates must have been formed more than 40
      million years ago. We also show that the N mRNA of a current mammalian
      bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes
      of persistently infected cultured cells. Our results provide the first evidence
      for endogenization of non-retroviral virus-derived elements in mammalian genomes
      and give novel insights not only into generation of endogenous elements, but also
      into a role of bornavirus as a source of genetic novelty in its host.

PMID- 20054396
TI  - Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma.
AB  - A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred
      by studying immunoglobulin genes in human lymphomas and by engineering mouse
      models, but genetic and functional evidence for its oncogenic role in human
      lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling
      that is required for cell survival in the activated B-cell-like (ABC) subtype of
      diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required
      for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly
      10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the
      mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA
      interference genetic screen revealed that a BCR signalling component, Bruton's
      tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type
      CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and
      CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs
      in these ABC DLBCLs formed prominent clusters in the plasma membrane with low
      diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic
      mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM)
      signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL
      biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or
      mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one
      functionally critical residue of CD79B, the first ITAM tyrosine, was mutated.
      These mutations increased surface BCR expression and attenuated Lyn kinase, a
      feedback inhibitor of BCR signalling. These findings establish chronic active BCR
      signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several
      therapeutic strategies.

PMID- 20054397
TI  - High-performance genetically targetable optical neural silencing by light-driven
      proton pumps.
AB  - The ability to silence the activity of genetically specified neurons in a
      temporally precise fashion would provide the opportunity to investigate the
      causal role of specific cell classes in neural computations, behaviours and
      pathologies. Here we show that members of the class of light-driven outward
      proton pumps can mediate powerful, safe, multiple-colour silencing of neural
      activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables
      near-100% silencing of neurons in the awake brain when virally expressed in the
      mouse cortex and illuminated with yellow light. Arch mediates currents of several
      hundred picoamps at low light powers, and supports neural silencing currents
      approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch
      spontaneously recovers from light-dependent inactivation, unlike light-driven
      chloride pumps that enter long-lasting inactive states in response to light.
      These properties of Arch are appropriate to mediate the optical silencing of
      significant brain volumes over behaviourally relevant timescales. Arch function
      in neurons is well tolerated because pH excursions created by Arch illumination
      are minimized by self-limiting mechanisms to levels comparable to those mediated
      by channelrhodopsins or natural spike firing. To highlight how proton pump
      ecological and genomic diversity may support new innovation, we show that the
      blue-green light-drivable proton pump from the fungus Leptosphaeria maculans
      (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus
      enabling alongside other developed reagents the potential for independent
      silencing of two neural populations by blue versus red light. Light-driven proton
      pumps thus represent a high-performance and extremely versatile class of
      'optogenetic' voltage and ion modulator, which will broadly enable new
      neuroscientific, biological, neurological and psychiatric investigations.

PMID- 20054398
TI  - Ligand-specific regulation of the extracellular surface of a G-protein-coupled
      receptor.
AB  - G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate
      most cellular responses to hormones and neurotransmitters. They are the largest
      group of therapeutic targets for a broad spectrum of diseases. Recent crystal
      structures of GPCRs have revealed structural conservation extending from the
      orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G
      protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs
      is remarkably diverse and is therefore an ideal target for the discovery of
      subtype-selective drugs. However, little is known about the functional role of
      the ECS in receptor activation, or about conformational coupling of this surface
      to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate
      ligand-specific conformational changes around a central structural feature in the
      ECS of the beta(2) adrenergic receptor: a salt bridge linking extracellular loops
      2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit
      different efficacies towards G-protein activation (agonist, neutral antagonist
      and inverse agonist) also stabilize distinct conformations of the ECS. We thereby
      demonstrate conformational coupling between the ECS and the orthosteric binding
      site, showing that drugs targeting this diverse surface could function as
      allosteric modulators with high subtype selectivity. Moreover, these studies
      provide a new insight into the dynamic behaviour of GPCRs not addressable by
      static, inactive-state crystal structures.

PMID- 20054399
TI  - The Dbf4-Cdc7 kinase promotes S phase by alleviating an inhibitory activity in
      Mcm4.
AB  - Eukaryotic DNA replication uses kinase regulatory pathways to facilitate
      coordination with other processes during cell division cycles and response to
      environmental cues. At least two cell cycle-regulated protein kinase systems, the
      S-phase-specific cyclin-dependent protein kinases (S-CDKs) and the Dbf4-Cdc7
      kinase (DDK, Dbf4-dependent protein kinase) are essential activators for
      initiation of DNA replication. Although the essential mechanism of CDK activation
      of DNA replication in Saccharomyces cerevisiae has been established, exactly how
      DDK acts has been unclear. Here we show that the amino terminal serine/threonine
      rich domain (NSD) of Mcm4 has both inhibitory and facilitating roles in DNA
      replication control and that the sole essential function of DDK is to relieve an
      inhibitory activity residing within the NSD. By combining an mcm4 mutant lacking
      the inhibitory activity with mutations that bypass the requirement for CDKs for
      initiation of DNA replication, we show that DNA synthesis can occur in G1 phase
      when CDKs and DDK are limited. However, DDK is still required for efficient S
      phase progression. In the absence of DDK, CDK phosphorylation at the distal part
      of the Mcm4 NSD becomes crucial. Moreover, DDK-null cells fail to activate the
      intra-S-phase checkpoint in the presence of hydroxyurea-induced DNA damage and
      are unable to survive this challenge. Our studies establish that the eukaryote
      specific NSD of Mcm4 has evolved to integrate several protein kinase regulatory
      signals for progression through S phase.

PMID- 20054402
TI  - High-Performance Silicon Nanopore Hemofiltration Membranes.
AB  - Silicon micromachining provides the precise control of nanoscale features that
      can be fundamentally enabling for miniaturized, implantable medical devices.
      Concerns have been raised regarding blood biocompatibility of silicon-based
      materials and their application to hemodialysis and hemofiltration. A high
      performance ultrathin hemofiltration membrane with monodisperse slit-shaped pores
      was fabricated using a sacrificial oxide technique and then surface-modified with
      poly(ethylene glycol) (PEG). Fluid and macromolecular transport matched model
      predictions well. Protein adsorption, fouling, and thrombosis were significantly
      inhibited by the PEG. The membrane retained hydraulic permeability and molecular
      selectivity during a 90 hour hemofiltration experiment with anticoagulated bovine
      whole blood. This is the first report of successful prolonged hemofiltration with
      a silicon nanopore membrane. The results demonstrate feasibility of renal
      replacement devices based on these membranes and materials.

PMID- 20054403
TI  - Stochastic spatio-temporal dynamic model for gene/protein interaction network in
      early Drosophila development.
AB  - In order to investigate the possible mechanisms for eve stripe formation of
      Drosophila embryo, a spatio-temporal gene/protein interaction network model is
      proposed to mimic dynamic behaviors of protein synthesis, protein decay, mRNA
      decay, protein diffusion, transcription regulations and autoregulation to analyze
      the interplay of genes and proteins at different compartments in early
      embryogenesis. In this study, we use the maximum likelihood (ML) method to
      identify the stochastic 3-D Embryo Space-Time (3-DEST) dynamic model for
      gene/protein interaction network via 3-D mRNA and protein expression data and
      then use the Akaike Information Criterion (AIC) to prune the gene/protein
      interaction network. The identified gene/protein interaction network allows us
      not only to analyze the dynamic interplay of genes and proteins on the border of
      eve stripes but also to infer that eve stripes are established and maintained by
      network motifs built by the cooperation between transcription regulations and
      diffusion mechanisms in early embryogenesis. Literature reference with the wet
      experiments of gene mutations provides a clue for validating the identified
      network. The proposed spatio-temporal dynamic model can be extended to
      gene/protein network construction of different biological phenotypes, which
      depend on compartments, e.g. postnatal stem/progenitor cell differentiation.

PMID- 20054404
TI  - Microarray data analysis of gene expression evolution.
AB  - Microarrays are becoming a widely used tool to study gene expression evolution. A
      recent paper by Wang and Rekaya describes a comprehensive study of gene
      expression evolution by microarray. The work provides a perspective to study gene
      expression evolution in terms of functional enrichment and promoter conservation.
      It was found that gene expression patterns are highly conserved in some
      biological processes, but the correlation between promoter and gene expression is
      insignificant. This scope of this work and future improvement to study gene
      expression evolution will be discussed in this article.

PMID- 20054405
TI  - Evolution and origin of HRS, a protein interacting with Merlin, the
      Neurofibromatosis 2 gene product.
AB  - Hepatocyte growth factor receptor tyrosine kinase substrate (HRS) is an endosomal
      protein required for trafficking receptor tyrosine kinases from the early
      endosome to the lysosome. HRS interacts with Merlin, the Neurofibromatosis 2
      (NF2) gene product, and this interaction may be important for Merlin's tumor
      suppressor activity. Understanding the evolution, origin, and structure of HRS
      may provide new insight into Merlin function. We show that HRS homologs are
      present across a wide range of Metazoa with the yeast Vps27 protein as their most
      distant ancestor. The phylogenetic tree of the HRS family coincides with species
      evolution and divergence, suggesting a unique function for HRS. Sequence
      alignment shows that various protein domains of HRS, including the VHS domain,
      the FYVE domain, the UIM domain, and the clathrin-binding domain, are conserved
      from yeast to multicellular organisms. The evolutionary transition from
      unicellular to multicellular organisms was accompanied by the appearance of a
      binding site for Merlin, which emerges in the early Metazoa after its separation
      from flatworms. In addition to the region responsible for growth suppression, the
      Merlin-binding and STAM-binding domains of HRS are conserved among multicellular
      organisms. The residue equivalent to tyrosine-377, which is phosphorylated in the
      human HRS protein, is highly conserved throughout the HRS family. Three
      additional conserved boxes lacking assigned functions are found in the HRS
      proteins of Metazoa. While boxes 1 and 3 may constitute the Eps-15-and Snx1
      binding sites, respectively, box 2, containing the residue equivalent to tyrosine
      377, is likely to be important for HRS phosphorylation. While several functional
      domains are conserved throughout the HRS family, the STAM-binding, Merlin
      binding, and growth suppression domains evolved in the early Metazoa around the
      time the Merlin protein emerged. As these domains appear during the transition to
      multicellularity, their functional roles may be related to cell-cell interaction.

PMID- 20054406
TI  - Characteristics of transcriptional activity in nonlinear dynamics of genetic
      regulatory networks.
AB  - Microarray measurements of mRNA abundances is a standard tool for evaluation of
      transcriptional activity in functional genomics. The methodology underlying these
      measurements assumes existence of a direct link between transcription levels,
      that is, gene-specific mRNA copy numbers present in the cell, and transcription
      rates, that is, the numbers of gene-specific mRNA molecules synthesized per unit
      of time. In this paper, the question of whether or not such a tight
      interdependence may exist is examined in the context of nonlinear dynamics of
      genetic regulatory networks. Using the equations of chemical kinetics, a model
      has been constructed that is capable of explicitly taking into consideration
      nonlinear interactions between the genes through the teamwork of transcription
      factors. Jacobian analysis of stability has shown that steady state equilibrium
      is impossible in such systems. However, phase space compressibility is found to
      be negative, thus suggesting that asymptotic stability may exist and assume
      either the form of limit cycle or of a chaotic attractor. It is argued that in
      rapidly fluctuating or chaotic systems, direct evaluation of transcription rates
      through transcription levels is highly problematic. It is also noted that even if
      a hypothetical steady state did exist, the knowledge of transcription levels
      alone would not be sufficient for the evaluation of transcription rates; an
      additional set of parameters, namely the mRNA decay rates, would be required. An
      overall conclusion of the work is that the measurements of mRNA abundances are
      not truly representative of the functionality of genes and structural fidelity of
      the genetic codes.

PMID- 20054407
TI  - Hereditary Inclusion Body Myopathy (HIBM2).
AB  - Hereditary inclusion body myopathy type 2 (HIBM2) is a myopathy characterized by
      progressive muscle weakness with early adult onset. The disease is the result of
      a recessive mutation in the Glucosamine (UDP-N-acetyl)-2-epimerase/N
      acetylmannosamine kinase gene (GNE), which results in reduced enzyme function and
      sialic acid levels. A majority of individuals with HIBM2 are from Iranian-Jewish
      or Japanese decent, but isolated cases have been identified world wide. This
      article reviews the diagnostic criteria for HIBM2. Current research with a
      highlight on the biology of the disease and the role of GNE in the sialic acid
      pathway are assessed. Finally, therapeutic investigations and animal models are
      discussed with a focus on future studies to better understand the pathology of
      Hereditary Inclusion Body Myopathy and move therapeutic agents towards clinical
      trials.

PMID- 20054408
TI  - Torus hyperplasia of the pyloric antrum.
AB  - Primary or idiopathic hypertrophy of the pyloric muscle in adult, so called torus
      hyperplasia, is an infrequent but an established entity. It is caused by a
      circular muscle hypertrophy affecting the lesser curvature near the pylorus.
      Since most of the lesions are difficult to differentiate from tumor, distal
      gastrectomy is usually preformed to rule out most causes of pyloric lesions
      including neoplastic ones through a pathological study. A 56-yr-old man with a
      family history of gastric cancer presented with abdominal discomfort of 1 month
      duration. Upper gastrointestinal endoscopy showed a 1.0 cm sized irregular
      submucosal lesion proximal to the pylorus to the distal antrum on the lesser
      curvature. On colonoscopy examination, a 1.5 cm sized protruding mass was noticed
      on the appendiceal orifice. Gastrectomy and cecectomy were done, and histological
      section revealed marked hypertrophy of the distal circular pyloric musculature
      and an appendiceal mucocele. To the best of our knowledge, this is the first case
      of torus hyperplasia with appendiceal mucocele which is found incidentally.

PMID- 20054409
TI  - GnRH agonist therapy to protect ovarian function in young Korean breast cancer
      patients.
AB  - The increased survival of patients with breast cancer has given rise to other
      problems associated with the complications of chemotherapy. One major
      complication is premature ovarian failure, an especially harmful outcome for
      women of reproductive age. This study was performed to evaluate the efficacy of
      GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast
      cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two
      women were enrolled and given subcutaneous injections of leuprolide acetate (3.75
      mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing
      hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed
      1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical
      symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH
      levels were normal in all patients 6 months after completing chemotherapy (8.0+/
      5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients
      complained of menopausal symptoms and 81.8% experienced recovery of menstruation.
      This report is the first trial of GnRHa as a treatment modality to protect
      ovarian function during adjuvant chemotherapy in young Korean breast cancer
      patients.

PMID- 20054410
TI  - Changing from bevacizumab to ranibizumab in age-related macular degeneration. Is
      it safe?
AB  - OBJECTIVE: To report our experiences in changing from intravitreal bevacizumab to
      ranibizumab in age-related macular degeneration (AMD). DESIGN: Retrospective case
      series. PARTICIPANTS AND METHODS: We retrospectively reviewed the records of 34
      patients (36 eyes) who were treated with monthly injections of intravitreal
      bevacizumab for six months and then switched to monthly injections of ranibizumab
      for 12 months. Best-corrected visual acuity measurements (BCVA), contact lens
      biomicroscopy, optical coherence tomography (OCT), and fluorescein angiography
      were performed at the baseline examination and then monthly. Chi-square test was
      used for statistical analysis. RESULTS: Following bevacizumab treatment, retinal
      thickness decreased (P = 0.033) while BCVA improved (P = 0.040). Changing from
      bevacizumab to ranibizumab resulted in a transient decrease in BCVA (P = 0.045)
      and an increase in retinal thickness (P = 0.042). In addition, three eyes
      presented with a large subretinal hemorrhage. However, final retinal thickness
      was better than the initial thickness and the value following the bevacizumab
      course. No major ocular or systemic side effects were noted. CONCLUSIONS:
      Ranibizumab was clinically effective in the long term but the change of treatment
      from bevacizumab to a half-size molecule with less half-life in the vitreous such
      as ranibizumab contributed to a transient "instability" in the eye which may have
      triggered the large subretinal hemorrhage. There is insufficient experience
      reported in the literature in switching from one agent to another. A prospective
      study with controls is necessary to determine whether it is safe to change from
      one medication to another.

PMID- 20054412
TI  - Successful endonasal dacryocystorhinostomy in a patient with Wegener's
      granulomatosis.
AB  - Wegener's granulomatosis (WG) is one form of idiopathic autoimmune vasculitis.
      The disease has a predilection for the upper and lower respiratory tracts (lungs,
      nose, sinus), and kidneys. WG may be systemic, severe, and potentially lethal,
      but it may also be limited to the otolaryngological area or to the eyes and the
      orbits. Obstruction of the lacrimal pathway is a possible complication of the
      disease that affects approximately 7% of patients with WG. It usually occurs as a
      direct extension of sinonasal disease and typically is a late manifestation.
      Management of such a condition is generally viewed as difficult. We report the
      case of a patient with a quiescent WG limited to the otolaryngological area. This
      patient presented a bilateral obstruction of the nasolacrimal ducts caused by
      bilateral extensive adhesions in the nasal cavity. Because she had several
      episodes of left-side acute dacryocystitis which necessitated several courses of
      broad-spectrum antibiotics, she successfully underwent an endonasal endoscopic
      dacryocystorhinostomy using a diode laser and powered instrumentation. The
      authors describe the clinical case, the surgical technique, and review the
      literature.

PMID- 20054411
TI  - Vardenafil for the treatment of erectile dysfunction: an overview of the clinical
      evidence.
AB  - Many men with erectile dysfunction (ED) also have associated underlying
      cardiovascular and metabolic conditions, for which they are likely to be taking
      medication. Therefore, cardiovascular safety and potential drug interactions are
      two of the major concerns when using PDE-5 inhibitors in these patients. The PDE
      5 inhibitor, vardenafil, is characterized by a rapid onset of action, increased
      duration of erection, high rates of first-dose success and reliable efficacy that
      can be maintained with continued use. In both clinical trials and real-life
      observational studies, vardenafil has demonstrated a favorable efficacy and
      safety profile in men with ED, including those with associated underlying
      conditions such as diabetes, hypertension and dyslipidemia. Importantly, the
      concomitant use of medication for these conditions is not associated with any
      noteworthy changes in the efficacy and safety of vardenafil. The evidence
      presented in this review supports the use of vardenafil as a first-line treatment
      for men with ED, including those with underlying conditions.

PMID- 20054413
TI  - Toxoplasma retinochoroiditis in pregnancy: Using current evidence to inform
      management.
AB  - Toxoplasma retinochoroiditis in pregnancy may create considerable patient anxiety
      and is a dilemma for the treating ophthalmologist. A case report highlighting
      this clinical issue is presented followed by a review of the literature.
      Consensus in relation to the management of toxoplasma retinochoroiditis in
      pregnancy is lacking and is discussed.

PMID- 20054414
TI  - Role of prostaglandins and specific place in therapy of bimatoprost in the
      treatment of elevated intraocular pressure and ocular hypertension: A closer look
      at the agonist properties of bimatoprost and the prostamides.
AB  - Bimatoprost is the only representative of a novel class of prostaglandin
      ethanolamide (prostamide) compounds used therapeutically as an efficacious
      treatment for glaucoma. The pathways through which bimatoprost works to improve
      uveoscleral outflow to relieve elevated intraocular pressure are similar to those
      of the conventional prostaglandins used in glaucoma therapy, with some evidence
      of a preferential action at the trabecular meshwork. The pharmacology of
      bimatoprost is however, unclear. Pharmacological evidence supports a specific and
      distinct receptor-mediated agonist activity of bimatoprost at 'prostamide'
      receptors, which is selective to the prostamides as a class. However, other
      studies have reported either activity of bimatoprost at additional prostanoid and
      nonprostanoid receptors, or a conversion of bimatoprost to metabolites with
      agonist activity at prostaglandin FP receptors in the human eye. The formation of
      endogenous prostamides has been demonstrated in vivo, by a novel pathway
      involving the cyclooxygenase-2-mediated conversion of endogenous cannabinoid
      (endocannabinoid) substrates. Irrespective of the pharmacology of bimatoprost and
      the prostamides in general, further studies are needed to determine the
      biological role and biochemical pathology of prostamides in the human eye,
      particularly in glaucoma. Such studies may improve our understanding of
      uveoscleral flow and may offer new treatments for controlling intraocular
      pressure.

PMID- 20054415
TI  - Differences between the combination of the 25-gauge vitrectomy with
      phacoemulsification versus 20-gauge vitrectomy and phacofragmentation.
AB  - INTRODUCTION: In the present study we determine the differences observed between
      25-gauge-vitrectomy combined with phacoemulsification, and the 20-gauge
      vitrectomy combined with pars plana phacofragmentation. METHODS: A prospective
      study of a sample of 987 eyes of 661 patients randomly divided into two groups.
      25-gauge-vitrectomy plus phacoemulsification included 486 eyes, and 20-gauge
      vitrectomy plus phacofragmentation 501 eyes. We evaluated the differences at the
      time of the surgery, the intra-and postoperative complications, and the
      variations in intraocular pressure. RESULTS: The final visual outcome was similar
      in both groups. The most important differences between groups were: surgical time
      was faster in group 1 than in group 2, (mean time: 35.16 +/- 3.49, 44.74 +/- 5.30
      minutes). Intraoperative complications were more numerous in group 1. In group 1,
      postoperative low levels of intraocular pressure are present in all patients with
      2.77% of patients with hypotension (<8 mmHg), and three choroidal effusion. In
      group 2, intraocular lens decentration and retinal detachment are more frequent
      (2.38% and 1.39%, respectively). CONCLUSIONS: In the present study, both
      techniques have a similar number of complications and have a similar
      postoperative outcome, and are valid for the management of the pathologies
      selected.

PMID- 20054416
TI  - A modified technique of retrograde intubation dacryocystorhinostomy for proximal
      canalicular obstruction.
AB  - PURPOSE: To describe a modification of the retrograde intubation
      dacryocystorhinostomy (DCR) in patients with proximal canalicular obstruction.
      MATERIALS AND METHODS: Interventional case report of a 43-year-old female with a
      nine-month history of left epiphora following a road traffic accident involving
      the proximal lower canaliculus. An external DCR approach was performed. Following
      the creation of a lower canalicular pseudopunctum, the O'Donoghue silicone stent
      was introduced through the common ostium, out through the pseudopunctum of the
      lower canaliculus, and returned through the punctum of the normal upper
      canaliculus down through the common ostium into the nose. RESULTS: The patient
      experienced complete resolution of symptoms and on her last follow-up, two years
      later, her lower canaliculus was patent to syringing. CONCLUSION: This
      modification of the retrograde intubation DCR is an effective technique which
      decreases the intraoperative time needed to insert the tubes and minimises
      further trauma to the newly created punctal area.

PMID- 20054417
TI  - Bevacizumab (Avastin) for the management of anterior chamber neovascularization
      and neovascular glaucoma.
AB  - PURPOSE: To establish the efficacy and safety of intravitreal bevacizumab in
      reducing iris and anterior chamber angle neovascularization and managing
      neovascular glaucoma. DESIGN: Prospective interventional case series. PATIENT AND
      METHODS: Eleven eyes of 11 patients with iris and anterior chamber angle
      neovascularization with refractory intraocular pressure were treated with
      intravitreal injection of 1.25 mg bevacizumab (Avastin((R))). The study group
      included eight males and three females aged 23 to 77 years (average, 62 years).
      Out of the 11 cases, five had proliferative diabetic retinopathy, of whom two had
      undergone vitrectomy for tractional retinal detachment and vitreous hemorrhage,
      and six were secondary to ischemic central retinal vein occlusion (CRVO). All
      patients were followed for eight to 16 months (average, 10 months). RESULTS: Iris
      and anterior chamber angle neovascularization receded in all eyes after one to
      three injections at monthly intervals. In five eyes, neovascularization recurred
      during the follow-up period. The intraocular pressure normalized in one eye. Four
      eyes were controlled with anti-glaucoma drops. A cyclodestructive procedure was
      required in two eyes. An Ahmet drainage valve was implanted in four eyes,
      including one controlled with additional antiglaucoma drops and one in which the
      intraocular pressure remained high while on maximum antiglaucoma medication and a
      cyclodestructive procedure was scheduled. CONCLUSIONS: Bevacizumab appears to be
      effective in reducing iris and anterior chamber angle neovascularization and is
      likely to extend our therapeutic options in the management of neovascular
      glaucoma.

PMID- 20054418
TI  - Treatment options for ocular adnexal lymphoma (OAL).
AB  - Most lymphomas that involve the ocular adnexal structure are low grade, B cell,
      non-Hodgkin's lymphomas. The treatment depends upon the grade and stage of the
      disease. High grade lymhoma requires treatment with systemic chemotherapy whereas
      the localized low grade (extranodal marginal zone lymphoma) can be successfully
      managed with local radiotherapy. Chlamydia psittaci infection is associated with
      low grade ocular lymphoma; however there is wide geographic variation in the
      strength of this association. Blanket antibiotic therapy is not advised unless
      there is proof of an infective agent. The monoclonal antibody, rituximab, may be
      successful for CD20 positive lymphoma, although it is likely that rituximab will
      have better long-term results when used in combination with systemic
      chemotherapy.

PMID- 20054419
TI  - In vivo visualization of photoreceptor layer and lipofuscin accumulation in
      stargardt's disease and fundus flavimaculatus by high resolution spectral-domain
      optical coherence tomography.
AB  - INTRODUCTION: To assess photoreceptor (PR) layer morphology in patients with
      Stargardt's disease (STGD) and fundus flavimaculatus (FFM) using high resolution
      spectral domain optical coherence tomography (HD-OCT; OCT 4000 Cirrus, Humphrey
      Zeiss, San Leandro, CA). METHODS: This was a prospective observational case
      series. Sixteen consecutive patients with STGD and FFM underwent a complete
      ophthalmologic examination. Optical coherence tomography examination was
      performed with HD-OCT, a high-speed (27,000 axial scans per second) OCT system
      using spectral/Fourier domain detection, with an axial image resolution of 5 mum.
      RESULTS: A total of 31 eyes were included in the study. Transverse loss of the PR
      layer in the foveal region was shown by HD-OCT. Twenty eyes with clinically
      evident central atrophy had a disruption of either the Verhoeff's membrane (VM)
      or the layer corresponding to the interface of inner segment (IS) and outer
      segment (OS) of PR in the foveal region. Among these eyes, 12/20 eyes had a loss
      of the PR layer (loss of both VM and IS-OS interface) in the foveal region.
      Eleven eyes (11/31) without clinically evident central atrophy had an intact
      interface of IS and OS of PR centrally. Moreover, we observed hyperreflective
      deposits: type 1 lesions located within the retinal pigment epithelium (RPE)
      layer and at the level of the outer segments of PR, and type 2 lesions located at
      the level of the outer nuclear layer and clearly separated from the RPE layer.
      Type 1 lesions alone were associated with absence of loss of the PR layer in the
      foveal region in all eyes; type 2 lesions were always associated with presence of
      type 1 lesions, and often (8/12 eyes) associated with loss of the PR layer within
      the foveal region. Mean best-corrected visual acuity (BCVA) was significantly
      correlated with loss of the PR layer in the foveal region (P < 0.001), as well as
      to presence of type 2 flecks (P = 0.03). CONCLUSION: Type 2 deposits in STGD/FFM
      patients seem to represent a marker of the possible evolution towards foveal
      atrophy.

PMID- 20054420
TI  - Evaluation of aortic stiffness (aortic pulse-wave velocity) before and after
      elective abdominal aortic aneurysm repair procedures: a pilot study.
AB  - BACKGROUND: The main clinical criterion for abdominal aortic aneurysm (AAA)
      repair operations is an AAA diameter >/=5.5 cm. When AAAs increase in size,
      specific changes occur in the mechanical properties of the aortic wall. Pulse
      wave velocity (PWV) has been used as an indicator of vascular stiffness. A low
      PWV may predict AAA rupture risk and is an early predictor of cardiovascular
      mortality. METHODS: We investigated the prognostic value of PWV before and after
      elective AAA repair procedures. Twenty four patients scheduled for an open AAA
      repair underwent a preoperative carotid-femoral aortic PWV measurement. A second
      aortic PWV measurement was carried out 6 months postoperatively. RESULTS: The
      mean aortic PWV increased from 7.84 +/- 1.85 preoperatively to 10.08 +/- 1.57
      m/sec 6 months postoperatively (mean change: 2.25; 95% confidence interval 1.4 to
      3.1 m/sec; p<0.0001). The preprocedural PWV measurement did not correlate with
      AAA diameter (Spearman's rank correlation coefficient rho=0.12; p=0.59).
      CONCLUSIONS: Whether the increase in aortic PWV postoperatively suggests a
      decreased cardiovascular risk following AAA repair remains to be established.
      Aortic PWV should also be investigated as an adjunct tool for assessing AAA
      rupture risk.

PMID- 20054421
TI  - Health measurement scales: methodological issues.
AB  - Health scales or indices are composite tools aiming to measure a variety of
      clinical conditions, behaviors, attitudes and beliefs that are difficult to be
      measured quantitatively. During the past years, these tools have been extensively
      used in cardiovascular disease prevention. The already proposed scales have shown
      good ability in assessing individual characteristics, but had moderate predictive
      ability in relation to the development of chronic diseases and various other
      health outcomes. In this review, methodological issues for the development of
      health scales are discussed. Specifically, the selection of the appropriate
      number of components, the selection of classes for each component, the use of
      weights of scale components and the role of intra- or inter-correlation between
      components are discussed. Based on the current literature the use of components
      with large number of classes, as well as the use of specific weights for each
      scale component and the low-to-moderate inter-correlation rate between the
      components, is suggested in order to increase the diagnostic accuracy of the
      tool.

PMID- 20054422
TI  - A Dynamical Shape Prior for LV Segmentation from RT3D Echocardiography.
AB  - Real-time three-dimensional (RT3D) echocardiography is the newest generation of
      three-dimensional (3-D) echocardiography. Segmentation of RT3D echocardiographic
      images is essential for determining many important diagnostic parameters. In
      cardiac imaging, since the heart is a moving organ, prior knowledge regarding its
      shape and motion patterns becomes an important component for the segmentation
      task. However, most previous cardiac models are either static models (SM), which
      neglect the temporal coherence of a cardiac sequence or generic dynamical models
      (GDM), which neglect the inter-subject variability of cardiac motion. In this
      paper, we present a subject-specific dynamical model (SSDM) which simultaneously
      handles inter-subject variability and cardiac dynamics (intra-subject
      variability). It can progressively predict the shape and motion patterns of a new
      sequence at the current frame based on the shapes observed in the past frames.
      The incorporation of this SSDM into the segmentation process is formulated in a
      recursive Bayesian framework. This results in a segmentation of each frame based
      on the intensity information of the current frame, as well as on the prediction
      from the previous frames. Quantitative results on 15 RT3D echocardiographic
      sequences show that automatic segmentation with SSDM is superior to that of
      either SM or GDM, and is comparable to manual segmentation.

PMID- 20054423
TI  - A Preventive Intervention Program for Urban African American Youth Attending an
      Alternative Education Program: Background, Implementation, and Feasibility.
AB  - This paper presents background, implementation, and feasibility findings
      associated with planning and conducting an after-school intervention program in
      an alternative education setting designed to prevent the initiation and
      escalation of violence and substance abuse among urban African American youth at
      high risk for life-long problem behaviors. Evolving from earlier preventive
      interventions implemented in clinic and school settings, the program, entitled
      The Village Model of Care, consisted of structured group mentoring, parental
      support, and community outreach services administered to alternative education
      students and their primary caregiver(s) during the school year. Over a two-year
      intake period, 109 youth participated in the present process evaluation study.
      Findings from the study not only provided relevant demographic information on the
      characteristics of youth likely to be included in such programs but also
      indicated the importance of including the family in the rehabilitation effort and
      the need for school administrative system support for the underlying alternative
      education approach. The information presented in this report has a direct bearing
      on the planning of future prevention efforts conducted in similar settings that
      are aimed at reducing problem behaviors and promoting positive lifestyles among
      high-risk youth.

PMID- 20054424
TI  - Preliminary Evaluations of a Self-Contained Anthropomorphic Transfemoral
      Prosthesis.
AB  - This paper presents a self-contained powered knee and ankle prosthesis, intended
      to enhance the mobility of transfemoral amputees. A finite-state based impedance
      control approach, previously developed by the authors, is used for the control of
      the prosthesis during walking and standing. Experiments on an amputee subject for
      level treadmill and overground walking are described. Knee and ankle joint angle,
      torque, and power data taken during walking experiments at various speeds
      demonstrate the ability of the prosthesis to provide a functional gait that is
      representative of normal gait biomechanics. Measurements from the battery during
      level overground walking indicate that the self-contained device can provide more
      than 4500 strides, or 9 km, of walking at a speed of 5.1 km/h between battery
      charges.

PMID- 20054426
TI  - Personal Guidance System for People with Visual Impairment: A Comparison of
      Spatial Displays for Route Guidance.
AB  - This article reports on a study of route guidance using a navigation system that
      receives location information from a Global Positioning System receiver. Fifteen
      visually impaired participants traveled along 50-meter (about 164-foot) paths in
      each of five conditions that were defined by the type of display interface used.
      One of the virtual displays-virtual speech-led to the shortest travel times and
      the highest subjective ratings, despite concerns about the use of headphones.

PMID- 20054425
TI  - Hedonic Homeostatic Dysregulation as a Driver of Drug-Seeking Behavior.
AB  - Drug addiction can be defined by a compulsion to seek and take drug and loss of
      control in limiting intake, and the excessive drug taking derives from multiple
      motivational mechanisms. One such mechanism is the emergence of a negative
      emotional state when access to the drug is prevented, reflecting hedonic
      homeostatic dysregulation. Excessive drug taking then results in part via the
      construct of negative reinforcement. The negative emotional state that drives
      such negative reinforcement is hypothesized to derive from dysregulation of key
      neurochemical elements involved in reward and stress within basal forebrain
      structures, including the ventral striatum and extended amygdala. Specific
      neurochemical elements in these structures include not only decreases in reward
      neurotransmission, such as decreases in dopamine and opioid peptide function in
      the ventral striatum, but also recruitment of brain stress systems, such as
      corticotropin-releasing factor (CRF), in the extended amygdala. Chronic exposure
      or extended access to self-administration of all major drugs of abuse produces
      during abstinence increases in reward thresholds, increases in aversive anxiety
      like responses, increases in extracellular levels of CRF in the central nucleus
      of the amygdala, and increases in drug self-administration. CRF receptor
      antagonists block excessive drug intake produced by dependence. A combination of
      decreased reward system function and increased brain stress response system
      function is hypothesized to be responsible for hedonic homeostatic dysregulation
      that drives drug seeking behavior in dependence. Such hedonic dysregulation is
      hypothesized to extend into protracted abstinence to provide a residual negative
      emotional state that enhances the salience of cues eliciting drug seeking and
      relapse.

PMID- 20054427
TI  - Hemispheric differences in word-meaning processing: Alternative interpretations
      of current evidence.
AB  - BACKGROUND: Drawing heavily on results from studies with divided visual field
      (dvf) presentation, current models of hemispheric differences in word semantic
      processing converge on a proposal (henceforth, "the standard model") that is
      increasingly being applied in studies of individuals with brain damage. According
      to this model, left hemisphere processes focus word meanings to their core,
      whereas right hemisphere processes keep wider representations active.  AIMS: This
      paper has three aims: (a) to raise concerns about methodological aspects of the
      dvf studies that are usually cited in support for the standard model,
      specifically assumptions about interpretation of lateral dvf prime presentation
      and priming measures; (b) to highlight areas of further research and theoretical
      clarification, with reference to studies with central presentation and general
      models of word-meaning processing; and (c) to discuss the implications of these
      concerns for deriving a model of hemispheric differences in word-meaning
      processing, using evidence from paired word priming studies as an example.  MAIN
      CONTRIBUTION: The paper discusses problematic assumptions about paired word
      priming studies of hemispheric contributions to word semantic processing and
      proposes further research to clarify these assumptions. Furthermore, it
      introduces an alternative interpretation of the available data, which provides a
      more parsimonious account of hemispheric engagement in the paired word semantic
      priming task.  CONCLUSIONS: Current evidence about hemispheric differences in
      word-meaning processing is far from conclusive. It is important to consider
      alternative interpretations of the available evidence when applying models based
      on this evidence to the study of language disorders. The alternative account
      proposed in this paper suggests that LH processing, rather than generally
      reducing activated word meanings to their core, is important for maintaining
      meanings that are unambiguous and consistent.

PMID- 20054429
TI  - Imageability effects on sentence judgement by right-brain-damaged adults.
AB  - BACKGROUND: For decades researchers assumed visual image generation was the
      province of the right hemisphere. The lack of corresponding evidence was only
      recently noted, yet conflicting results still leave open the possibility that the
      right hemisphere plays a role. This study assessed imagery generation in adult
      participants with and without right hemisphere damage (RHD). Imagery was
      operationalised as the activation of representations retrieved from long-term
      memory similar to those that underlie sensory experience, in the absence of the
      usual sensory stimulation, and in the presence of communicative stimuli.  AIMS:
      The primary aim of the study was to explore the widely held belief that there is
      an association between the right hemisphere and imagery generation ability. We
      also investigated whether visual and visuo-motor imagery generation abilities
      differ in adults with RHD.  METHODS #ENTITYSTARTX00026; PROCEDURES: Participants
      included 34 adults with unilateral RHD due to cerebrovascular accident and 38
      adults who served as non-brain-damaged (NBD) controls. To assess the potential
      effects of RHD on the processing of language stimuli that differ in imageability,
      participants performed an auditory sentence verification task. Participants
      listened to high- and low-imageability sentences from Eddy and Glass (1981) and
      indicated whether each sentence was true or false. The dependent measures for
      this task were performance accuracy and response times (RT).  OUTCOMES
      #ENTITYSTARTX00026; RESULTS: In general, accuracy was higher, and response time
      lower, for low-imagery than for high-imagery items. Although NBD participants'
      RTs for low-imagery items were significantly faster than those for high-imagery
      items, this difference disappeared in the group with RHD. We confirmed that this
      result was not due to a speed-accuracy trade-off or to syntactic differences
      between stimulus sets. A post hoc analysis also suggested that the group with RHD
      was selectively impaired in motor, rather than visual, imagery generation. 
      CONCLUSIONS: The disproportionately high RT of participants with RHD in response
      to low-imagery items suggests that these items had other properties that made
      their verification difficult for this population. The nature and extent of right
      hemisphere patients' deficits in processing different types of imagery should be
      considered. In addition, the capacity of adults with RHD to generate visual and
      motor imagery should be investigated separately in future studies.

PMID- 20054428
TI  - Cardiovascular Stem Cells in Regenerative Medicine: Ready for Prime Time?
AB  - Restoration of cardiovascular function is the ultimate goal of stem cell-based
      therapy. In principle, cardiovascular stem cells can improve cardiac function via
      de novo cardiomyogenesis, enhanced myocardial neovascularization, and prevention
      of post-infarct remodeling. Stem cell transplantation to improve cardiac function
      has received mixed results in human clinical trials. These early data suggest
      that a critical reassessment of the scientific basis to stem cell-based therapy
      is needed in order to bring this highly promising treatment modality to
      mainstream clinical care.

PMID- 20054430
TI  - Gesture and aphasia: Helping hands?
AB  - BACKGROUND: The study of communicative gestures is one of considerable interest
      for aphasia, in relation to theory, diagnosis, and treatment. Significant
      limitations currently permeate the general (psycho)linguistic literature on
      gesture production, and attention to these limitations is essential for both
      continued investigation and clinical application of gesture for people with
      aphasia.  AIMS: The aims of this paper are to discuss issues imperative to
      advancing the gesture production literature and to provide specific suggestions
      for applying the material herein to studies in gesture production for people with
      aphasia.  MAIN CONTRIBUTION: Two primary perspectives in the gesture production
      literature are distinct in their proposals about the function of gesture, and
      about where gesture arises in the communication stream. These two perspectives
      will be discussed, along with three elements considered to be prerequisites for
      advancing the research on gesture production. These include: operational
      definitions, coding systems, and the temporal synchrony characteristics of
      gesture.  CONCLUSIONS: Addressing the specific elements discussed in this paper
      will provide essential information for both continued investigation and clinical
      application of gesture for people with aphasia.

PMID- 20054431
TI  - Variable Selection in Nonparametric Varying-Coefficient Models for Analysis of
      Repeated Measurements.
AB  - Nonparametric varying-coefficient models are commonly used for analysis of data
      measured repeatedly over time, including longitudinal and functional responses
      data. While many procedures have been developed for estimating the varying
      coefficients, the problem of variable selection for such models has not been
      addressed. In this article, we present a regularized estimation procedure for
      variable selection that combines basis function approximations and the smoothly
      clipped absolute deviation (SCAD) penalty. The proposed procedure simultaneously
      selects significant variables with time-varying effects and estimates the nonzero
      smooth coefficient functions. Under suitable conditions, we have established the
      theoretical properties of our procedure, including consistency in variable
      selection and the oracle property in estimation. Here the oracle property means
      that the asymptotic distribution of an estimated coefficient function is the same
      as that when it is known a priori which variables are in the model. The method is
      illustrated with simulations and two real data examples, one for identifying risk
      factors in the study of AIDS and one using microarray time-course gene expression
      data to identify the transcription factors related to the yeast cell cycle
      process.

PMID- 20054432
TI  - Effect of the mechanical activation on size reduction of crystalline
      acetaminophen drug particles.
AB  - The decrease in particle size may offer new properties to drugs. In this study,
      we investigated the size reduction influence of the acetaminophen (C(8)H(9)O(2)N)
      particles by mechanical activation using a dry ball mill. The activated samples
      with the average size of 1 microm were then investigated in different time
      periods with the infrared (IR), inductively coupled plasma (ICP), atomic force
      microscopy (AFM), and X-ray diffraction (XRD) methods. The results of the IR and
      XRD images showed no change in the drug structure after the mechanical activation
      of all samples. With the peak height at full width at half maximum from XRD and
      the Scherrer equation, the size of the activated crystallite samples illustrated
      that the AFM images were in sound agreement with the Scherrer equation. According
      to the peaks of the AFM images, the average size of the particles in 30 hours of
      activation was 24 nm with a normal particle distribution. The ICP analysis
      demonstrated the presence of tungsten carbide particle impurities after
      activation from the powder sample impacting with the ball and jar. The greatest
      reduction in size was after milling for 30 hours.

PMID- 20054433
TI  - Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin
      against an in vivo intracellular Salmonella model.
AB  - Pluronic based core-shell nanostructures encapsulating gentamicin were designed
      in this study. Block copolymers of (PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na)
      were blended with PAA(-) Na(+) and complexed with the polycationic antibiotic
      gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic
      diameter of 210 nm, zeta potentials of -0.7 (+/-0.2), and incorporated
      approximately 20% by weight of gentamicin. Nanostructures upon co-incubation with
      J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures
      administered in vivo either at multiple dosage of 5 microg g(-1) or single dosage
      of 15 microg g(-1) in AJ-646 mice infected with Salmonella resulted in
      significant reduction of viable bacteria in the liver and spleen.
      Histopathological evaluation for concentration-dependent toxicity at a dosage of
      15 microg g(-1) revealed mineralized deposits in 50% kidney tissues of free
      gentamicin-treated mice which in contrast was absent in nanostructure-treated
      mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and
      improve in vivo bacterial clearance.

PMID- 20054435
TI  - Optimization of the preparation process of vinblastine sulfate (VBLS)-loaded
      folate-conjugated bovine serum albumin (BSA) nanoparticles for tumor-targeted
      drug delivery using response surface methodology (RSM).
AB  - Response surface methodology (RSM) was used to optimize the process of preparing
      bovine serum albumin (BSA) nanoparticles by desolvation, then the resulting BSA
      nanoparticles (BSANPs) were conjugated with folate to produce a drug carrier
      system that can specifically target tumors. The anticancer drug, vinblastine
      sulfate (VBLS), was loaded to this tumor-specific drug carrier system for the
      purpose of overcoming the nonspecific targeting characteristics and side effects
      of the drug. A central composite design was applied for modeling the process,
      which was composed of four independent variables, namely BSA concentration, the
      rate of adding ethanol (ethanol rate), ethanol amount, and the degree of
      crosslinking. The mean particle size and residual amino groups of the BSANPs were
      chosen as response variables. The interactive effects of the four independent
      variables on the response variables were studied. The characteristics of the
      nanoparticles; such as amount of folate conjugation, drug entrapment efficiency,
      drug-loading efficiency, surface morphology and release kinetics in vitro were
      investigated. Optimum conditions for preparing desired BSANPs, with a mean
      particle size of 156.6 nm and residual amino groups of 668.973 nM/mg, were
      obtained. The resulting folate-conjugated BSANPs (FA-BSANPs) showed a drug
      entrapment efficiency of 84.83% and drug-loading efficiency of 42.37%,
      respectively, and the amount of folate conjugation was 383.996 microM/g BSANPs.
      The results of this study indicate that using FA-BSANPs as a drug carrier system
      could be effective in targeting VBLS-sensitive tumors in the future.

PMID- 20054436
TI  - Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the
      Alpha-1 Foundation DNA and Tissue Bank.
AB  - INTRODUCTION: Intravenous augmentation therapy with purified intravenous alpha-1
      antitrypsin replaces the deficient protein and is the only currently approved
      treatment for alpha-1 antitrypsin deficiency (AATD) related lung disease. While
      augmentation therapy has been available for more than 20 years, there are a
      limited number of studies evaluating the effect of augmentation on lung function.
      MATERIAL AND METHODS: We examined the decline in forced expiratory volume in one
      second (FEV(1)) in patients enrolled in the Alpha-1 Foundation DNA and Tissue
      Bank in relation to the use or not of alpha-1 antitrypsin augmentation therapy.
      For the purpose of our analysis we included 164 patients with AATD and PI ZZ
      genotype. RESULTS: Mean age of the patients was 60 years, 52% were females, 94%
      were white and 78% ex-smokers. The mean FEV(1) at baseline was 1.7 L and the mean
      FEV(1) % of predicted was 51.3%. The mean follow-up time was 41.7 months. A total
      of 124 (76%) patients received augmentation therapy (augmented group) while 40
      patients (24%) did not received it (non-augmented group). When adjusted by age at
      baseline, sex, smoking status, baseline FEV(1) % of predicted, the mean overall
      change in FEV(1) was 47.6 mL/year, favoring the augmented group (DeltaFEV(1) 10.6
      +/- 21.4 mL/year) in comparison with the non-augmented group (DeltaFEV(1) -36.96
      +/- 12.1 mL/year) (P = 0.05). Beneficial DeltaFEV(1) were observed in ex-smokers
      and the group with initial FEV(1) % of predicted of <50%. No differences were
      observed in mortality. CONCLUSIONS: In conclusion, augmentation therapy improves
      lung function in subjects with AATD when adjusted by age, gender, smoking status
      and baseline FEV(1) % of predicted. The beneficial effects were noted in ex
      smoker subjects with FEV(1) below 50% of predicted.

PMID- 20054434
TI  - Nanomedicine in pulmonary delivery.
AB  - The lung is an attractive target for drug delivery due to noninvasive
      administration via inhalation aerosols, avoidance of first-pass metabolism,
      direct delivery to the site of action for the treatment of respiratory diseases,
      and the availability of a huge surface area for local drug action and systemic
      absorption of drug. Colloidal carriers (ie, nanocarrier systems) in pulmonary
      drug delivery offer many advantages such as the potential to achieve relatively
      uniform distribution of drug dose among the alveoli, achievement of improved
      solubility of the drug from its own aqueous solubility, a sustained drug release
      which consequently reduces dosing frequency, improves patient compliance,
      decreases incidence of side effects, and the potential of drug internalization by
      cells. This review focuses on the current status and explores the potential of
      colloidal carriers (ie, nanocarrier systems) in pulmonary drug delivery with
      special attention to their pharmaceutical aspects. Manufacturing processes, in
      vitro/in vivo evaluation methods, and regulatory/toxicity issues of nanomedicines
      in pulmonary delivery are also discussed.

PMID- 20054437
TI  - Methods for Assessing Improvement in Specificity when a Biomarker is Combined
      with a Standard Screening Test.
AB  - Biomarkers that can be used in combination with established screening tests to
      reduce false positive rates are in considerable demand. In this article, we
      present methods for evaluating the diagnostic performance of combination tests
      that require positivity on a biomarker test in addition to a standard screening
      test. These methods rely on relative true and false positive rates to measure the
      loss in sensitivity and gain in specificity associated with the combination
      relative to the standard test. Inference about the relative rates follows from
      noting their interpretation as conditional probabilities. These methods are
      extended to evaluate combinations with continuous biomarker tests by introducing
      a new statistical entity, the relative receiver operating characteristic (rROC)
      curve. The rROC curve plots the relative true positive rate versus the relative
      false positive rate as the biomarker threshold for positivity varies. Inference
      can be made by applying existing ROC methodology. We illustrate the methods with
      two examples: a breast cancer biomarker study proposed by the Early Detection
      Research Network (EDRN) and a prostate cancer case-control study examining the
      ability of free prostate-specific antigen (PSA) to improve the specificity of the
      standard PSA test.

PMID- 20054438
TI  - Targeted therapy in melanoma.
AB  - Malignant melanoma is a highly lethal disease unless detected early. Single-agent
      chemotherapy is well tolerated but is associated with very low response rates.
      Combination chemotherapy and biochemotherapy may improve objective response rates
      but do not prolong survival and are associated with greater toxicity.
      Immunotherapeutic approaches such as highdose interleukin-2 are associated with
      durable responses in a small percentage of patients, but are impractical for many
      patients due to accessibility and toxicity issues. Elucidations of the molecular
      mechanisms of carcinogenesis in melanoma have expanded the horizon of opportunity
      to alter the natural history of the disease. Multiple signal transduction
      pathways seem to be aberrant and drugs that target them have been and continue to
      be in development. In this review we present data on the most promising targeted
      agents in development, including B-raf inhibitors and other signal transduction
      inhibitors, oligonucleotides, proteasome inhibitors, as well as inhibitors of
      angiogenesis. Most agents are in early phase trials although some have already
      reached phase III evaluation. As knowledge and experience with targeted therapy
      advance, new challenges appear to be arising particularly in terms of resistance
      and appropriate patient selection.

PMID- 20054439
TI  - Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an
      update of the Oregon Drug Effectiveness Review Project.
AB  - OBJECTIVE: To systematically review the general and comparative efficacy and
      safety of anakinra for rheumatoid arthritis. METHODS: We searched MEDLINE((R)),
      Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from
      1980 to April 2009. We manually searched reference lists of pertinent review
      articles and explored the Center for Drug Evaluation and Research database. For
      efficacy we included randomized controlled trials (RCTs) comparing anakinra with
      placebo or other biologics. For safety both experimental and observational
      studies were eligible. Two persons independently reviewed abstracts and full text
      articles and extracted relevant data. RESULTS: We included data from 3 RCTs
      comparing anakinra with placebo for rheumatoid arthritis (RA). The pooled
      relative risk (RR) of an ACR50 (American College of Rheumatology) response for
      anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67). Adjusted indirect
      comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR
      of 0.67 (95% CI 0.38 to 1.17) favoring the anti-TNF drugs. This result did not
      reach statistical significance. For safety, we included 9 experimental and
      observational studies of 24 weeks to 3 years duration. Up to 30% of patients
      withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7) of
      patients experienced an injection site reaction. CONCLUSIONS: Anakinra is an
      effective drug for treating RA. Indirect comparisons with adalimumab, etanercept
      and infliximab, however, showed a trend towards greater efficacy for the anti-TNF
      drugs. Anakinra also seems to be associated with comparably high rates of
      injection site reactions. These results should be taken into account when
      considering biologic therapy for patients with RA.

PMID- 20054441
TI  - Unannounced telephone interviews: A useful and positively received tool in the
      reinforcement of lifestyle intervention.
AB  - OBJECTIVES: Reinforcement is critical in dietary counseling, but is also time
      demanding. We evaluated the acceptability of frequent telephone interviews,
      including a 24-hour dietary recall, as a means of reinforcement after lifestyle
      intervention in healthy subjects at risk of diabetes. The aim of this report is
      to assess the following questions: Was the chosen frequency and duration of
      telephone reinforcement appropriate? What were the positive and negative aspects
      of receiving telephone interviews? METHODS: Seventy-seven nondiabetic relatives
      of patients with type 2 diabetes were included in a randomized controlled
      intervention study in which they received dietary education. Unannounced
      telephone calls were placed to follow adherence and for encouragement and
      support. After two years of intervention, the perceived appropriateness of the
      different aspects of receiving telephone interviews were evaluated by postal
      questionnaire. RESULTS: Telephone reinforcement was positively received by the
      participants. Relatively frequent telephone calls, as many as three times per
      month, were not considered disturbing or time consuming. Participants became
      aware of their own dietary habits through the interviews, which they appreciated.
      They found duration of follow-up between one and five years appropriate.
      CONCLUSIONS: Telephone interviews can be applied in lifestyle intervention
      programs in healthy at-risk individuals in which time constraints may otherwise
      prevent active persons from participating.

PMID- 20054440
TI  - New advances in the treatment of adult chronic immune thrombocytopenic purpura:
      role of thrombopoietin receptor-stimulating agents.
AB  - Decades of basic science and clinical research have led to an increased
      understanding of the pathophysiology of immune thrombocytopenic purpura (ITP),
      the processes underlying thrombopoiesis, and the treatment of chronic ITP. Now,
      new agents are available to treat ITP in a nonimmunosuppressive fashion. Lessons
      learned from the clinical trials of recombinant human thrombopoietin (TPO) have
      led to the development of a novel class of compounds: nonimmunogenic agonists of
      the thrombopoietin receptor. Representing the first nonimmunosuppressive agents
      to treat chronic refractory ITP in decades, medications such as romiplostim and
      eltrombopag were recently approved by the US Food and Drug Administration. These
      new agents offer physicians a new tool for treating difficult cases of ITP in
      their medical armamentarium. Additional TPO mimetics are also being developed
      that show promise in vitro, and await future development.

PMID- 20054442
TI  - Patient's preferences for health scenarios associated with hepatitis C and its
      treatment.
AB  - BACKGROUND AND AIM: Antiviral therapy with peg-interferon and ribavirin induces
      sustained virus eradication in 40%-80% of patients with chronic hepatitis C virus
      (HCV). We investigated patient views on their involvement in therapeutic decision
      making and on the desirability of disease and treatment-related outcomes.
      METHODS: The control preferences and visual analog scales were administered in a
      pencil and paper format to a series of 45 patients in order to assess their
      decisional role, preferences for scenarios of HCV disease and antiviral
      treatment, and estimates of success required to recommend treatment. RESULTS: The
      preferred decisional role of patients was passive in 26 (58%), collaborative in
      12 (27%) and active in 7 (15%). Median preference scores ranged from 0.30 to 0.90
      for scenarios of disease, from 0.05 to 0.80 for side effects and from 25% to 100%
      for estimates of benefit to recommend treatment. CONCLUSIONS: Our patients prefer
      to defer to the doctor the final decision in starting therapy in a context of
      shared decision making. Reported preferences for HCV scenarios are in the range
      discussed in the literature. The wide variability in the values attributed to
      side effects by patients with chronic hepatitis C as well as in expected
      probabilities of successful treatment suggests a need for decision analysis
      tailored to the individual patient.

PMID- 20054443
TI  - Development of fludarabine formulations in the treatment of chronic lymphocytic
      leukemia.
AB  - Fludarabine is an antineoplastic agent used in the treatment of hematological
      malignancies, particularly chronic lymphocytic leukemia (CLL) and indolent B-cell
      lymphoma. Because of its immunosuppressive effects, fludarabine has been added to
      reduced intensity conditioning regimens. The oral formulation of fludarabine has
      become widely available. Pharmacokinetic studies have shown that an oral dose of
      40 mg/m(2)/d would provide systemic drug exposure similar to the standard
      intravenous (IV) dose of 25 mg/m(2)/d. The oral dose can be taken once daily
      without any dietary restrictions. Dose adjustments are mandatory in patients with
      renal impairment to avoid increased toxicity. Several noncomparative trials in
      previously untreated and treated patients with CLL have shown that treatment with
      the oral formulation demonstrates similar efficacy compared to historical control
      groups treated with the IV formulation. The tolerability profile of oral
      fludarabine seems similar to that of the IV formulation. Myelosuppression and
      infectious complications are the most frequently reported adverse events.
      Gastrointestinal toxicity is more frequent with the oral formulation, but is
      usually of mild or moderate severity. Although oral fludarabine makes treatment
      more convenient, health care workers must be aware of the compliance behavior of
      each patient.

PMID- 20054444
TI  - Conivaptan and its role in the treatment of hyponatremia.
AB  - Hyponatremia is the most common electrolyte abnormality in hospitalized patients
      and is associated with increased morbidity and mortality. The recognition of the
      central role that arginin vasopressin plays in the pathogenesis of hyponatremia
      and the discovery that its actions are mediated by stimulation of V(1A) and V(2)
      receptors have led to the development of a new class of drugs, the arginin
      vasopressin antagonists. Conivaptan is a nonselective V(1A) and V(2) receptors
      antagonist that was the first of this class to be approved by the FDA for the
      management of euvolemic and hypervolemic hyponatremia. Its short-term safety and
      efficacy for the correction of hyponatremia have been established by multiple
      double-blind, randomized, controlled studies. Blocking the effects of arginin
      vasopressin on V(2) receptors produces aquaresis--the electrolyte-sparing
      excretion of water--an ideal approach to correct hypervolemic hyponatremia. The
      nonselectivity of conivaptan offers a theoretical advantage for its use in heart
      failure that may merit further exploration.

PMID- 20054446
TI  - Effect of combinations of antiviral drugs on herpes simplex encephalitis.
AB  - 2-Phenylamino-6-oxo-9-(4-hydroxybutyl)purine (HBPG) is a thymidine kinase
      inhibitor that prevents encephalitic death in mice caused by herpes simplex virus
      (HSV) types 1 and 2, although its potency is somewhat less than that of acyclovir
      (ACV). The present study was undertaken to determine the effect of combinations
      of HBPG and either ACV, phosphonoformate (PFA), or cidofovir (CDF) against HSV
      encephalitis. BALB/c mice were given ocular infections with HSV-1 or HSV-2, and
      treated twice daily intraperitoneally for five days with HBPG, alone or in
      combination with ACV, PFA, or CDF. Animals were observed daily for up to 30 days,
      and the day of death of each was recorded. All of the combinations showed
      additivity, and the combination of HBPG + ACV appeared to be synergistic, ie,
      protected more mice against HSV-1 encephalitis compared with each drug given
      alone. Delay of treatment with HBPG for up to two days was still effective in
      preventing HSV-2 encephalitis. The combination of the thymidine kinase inhibitor
      HBPG and the antiherpes drug ACV may have synergistic activity against HSV
      encephalitis. The development of a potent and safe combination therapy for the
      prevention and/or treatment of HSV infection of the central nervous system can
      improve the outcome of this infection in humans.

PMID- 20054447
TI  - Review of the pharmacology and clinical studies of micafungin.
AB  - Micafungin, like other members of the echinocandin class, has a unique mechanism
      of action that inhibits the synthesis of 1,3-beta-D glucans in the fungal cell
      wall. It has been approved for treatment of esophageal candidiasis, invasive
      candidiasis including candidemia, and for prophylaxis of Candida infections in
      patients undergoing hematopoietic stem cell transplantation. Although efficacy
      and safety have also been demonstrated in pediatric populations, micafungin is
      approved for this indication in Europe and Japan, but not in the United States.
      It has demonstrated activity against Candida spp. including those that are azole
      resistant as well as Aspergillus and a few other clinically important molds. It
      is administered intravenously as a once daily infusion and does not require dose
      adjustments for renal or moderate hepatic dysfunction. Its safety record,
      favorable tolerability profile, and few drug interactions make it an important
      agent for the treatment of invasive fungal infections.

PMID- 20054445
TI  - Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and
      potential therapeutic agent.
AB  - B-type natriuretic peptide (BNP) is a member of the natriuretic peptide family, a
      group of widely distributed, but evolutionarily conserved, polypeptide mediators
      that exert myriad cardiovascular effects. BNP is a potent vasodilator with
      mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in
      pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean
      pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in
      patients with pulmonary arterial hypertension (PAH). Elevated plasma BNP levels
      are associated with increased mortality in patients with PAH and a fall in BNP
      levels after therapy is associated with improved survival. These findings have
      important clinical implications in that a noninvasive blood test may be used to
      identify PAH patients at high-risk of decompensation and to guide pulmonary
      vasodilator therapy. BNP also has several biologic effects that could be
      beneficial to patients with PAH. However, lack of a convenient method for
      achieving sustained increases in circulating BNP levels has impeded the
      development of BNP as a therapy for treating pulmonary hypertension. New
      technologies that allow transdermal or oral administration of the natriuretic
      peptides have the potential to greatly accelerate research into therapeutic use
      of BNP for cor pulmonale and pulmonary vascular diseases. This review will
      examine the basic science and clinical research that has led to our understanding
      of the role of BNP in cardiovascular physiology, its use as a biomarker of right
      ventricular function and its therapeutic potential for managing patients with
      pulmonary vascular disease.

PMID- 20054448
TI  - Testing for Covariate Effect in the Cox Proportional Hazards Regression Model.
AB  - This paper presents methods for testing covariate effect in the Cox proportional
      hazards Model based on Kullback-Leibler divergence and Renyi's information
      measure. Renyi's measure is referred to as the information divergence of order
      gamma (gamma ? 1) between two distributions. In the limiting case gamma -> 1,
      Renyi's measure becomes Kullback-Leibler divergence. In our case, the
      distributions correspond to the baseline and one possibly due to a covariate
      effect. Our proposed statistics are simple transformations of the parameter
      vector in the Cox proportional hazards model, and are compared with the Wald,
      likelihood ratio and Score tests that are widely used in practice. Finally, the
      methods are illustrated using two real-life data sets.

PMID- 20054449
TI  - A different story on "Theory of Mind" deficit in adults with right hemisphere
      brain damage.
AB  - BACKGROUND: Difficulties in social cognition and interaction can characterise
      adults with unilateral right hemisphere brain damage (RHD). Some pertinent
      evidence involves their apparently poor reasoning from a "Theory of Mind"
      perspective, which requires a capacity to attribute thoughts, beliefs, and
      intentions in order to understand other people's behaviour. Theory of Mind is
      typically assessed with tasks that induce conflicting mental representations.
      Prior research with a commonly used text task reported that adults with RHD were
      less accurate in drawing causal inferences about mental states than at making non
      mental-state causal inferences from control texts. However, the Theory of Mind
      and control texts differed in the number and nature of competing discourse entity
      representations. This stimulus discrepancy, together with the explicit measure of
      causal inferencing, likely put the adults with RHD at a disadvantage on the
      Theory of Mind texts.  AIMS: This study revisited the question of Theory of Mind
      deficit in adults with RHD. The aforementioned Theory of Mind texts were used but
      new control texts were written to address stimulus discrepancies, and causal
      inferencing was assessed relatively implicitly. Adults with RHD were hypothesised
      not to display a Theory of Mind deficit under these conditions.  METHODS
      #ENTITYSTARTX00026; PROCEDURES: The participants were 22 adults with unilateral
      RHD from cerebrovascular accident, and 38 adults without brain damage.
      Participants listened to spoken texts that targeted either mental-state or non
      mental-state causal inferences. Each text was followed by spoken True/False probe
      sentences, to gauge target inference comprehension. Both accuracy and RT data
      were recorded. Data were analysed with mixed, two-way Analyses of Variance (Group
      by Text Type).  OUTCOMES #ENTITYSTARTX00026; RESULTS: There was a main effect of
      Text Type in both accuracy and RT analyses, with a performance advantage for the
      Theory of Mind/mental-state inference stimuli. The control group was faster at
      responding, and primed more for the target inferences, than the RHD group. The
      overall advantage for Theory of Mind texts was traceable to one highly
      conventional inference: someone tells a white lie to be polite. Particularly poor
      performance in mental-state causal inferencing was not related to neglect or
      lesion site for the group with RHD.  CONCLUSIONS: With appropriate stimulus
      controls and a relatively implicit measure of causal inferencing, this study
      found no "Theory of Mind" deficit for adults with RHD. The utility of the "Theory
      of Mind" construct is questioned. A better understanding of the social
      communication difficulties of adults with RHD will enhance clinical management in
      the future.

PMID- 20054450
TI  - PRAYER AND MARITAL INTERVENTION: A CONCEPTUAL FRAMEWORK.
AB  - Discomfort with the integration of spiritual activities into marital
      interventions may be a response by practitioners to the weakness of available
      conceptual frameworks. We offer a framework that allows for integration of prayer
      into marital interventions (educational or therapeutic), and argue that when
      culturally appropriate, prayer can serve multiple functions in interventions that
      are consistent with traditional goals of skill-based approaches. Several specific
      ways in which prayer can be either an alternative or an addition to existing
      intervention strategies are outlined. The potential negative effects of prayer
      for couples and the dangers of integrating prayer into programs are also
      discussed. We conclude that effective skill-based family intervention and
      prevention with some traditionally underserved groups may require increased
      attention to integration of spiritual practices that are common in those groups.

PMID- 20054451
TI  - Demonstration of a 140-GHz 1-kW Confocal Gyro-Traveling-Wave Amplifier.
AB  - The theory, design, and experimental results of a wideband 140-GHz 1-kW pulsed
      gyro-traveling-wave amplifier (gyro-TWA) are presented. The gyro-TWA operates in
      the HE(06) mode of an overmoded quasi-optical waveguide using a gyrating electron
      beam. The electromagnetic theory, interaction theory, design processes, and
      experimental procedures are described in detail. At 37.7 kV and a 2.7-A beam
      current, the experiment has produced over 820 W of peak power with a -3-dB
      bandwidth of 0.8 GHz and a linear gain of 34 dB at 34.7 kV. In addition, the
      amplifier produced a -3-dB bandwidth of over 1.5 GHz (1.1%) with a peak power of
      570 W from a 38.5-kV 2.5-A electron beam. The electron beam is estimated to have
      a pitch factor of 0.55-0.6, a radius of 1.9 mm, and a calculated perpendicular
      momentum spread of approximately 9%. The gyro-amplifier was nominally operated at
      a pulselength of 2 MUs but was tested to amplify pulses as short as 4 ns with no
      noticeable pulse broadening. Internal reflections in the amplifier were
      identified using these short pulses by time-domain reflectometry. The
      demonstrated performance of this amplifier shows that it can be applied to
      dynamic nuclear polarization and electron paramagnetic resonance spectroscopy.

PMID- 20054453
TI  - Tobacco use, exposure to secondhand smoke, and training on cessation counseling
      among nursing students: cross-country data from the Global Health Professions
      Student Survey (GHPSS), 2005-2009.
AB  - The Nursing Global Health Professions Student Survey (GHPSS) has been conducted
      in schools in 39 countries and the Gaza Strip/West Bank (identified as "sites"
      for the remainder of this paper). In half the sites, over 20% of the students
      currently smoked cigarettes, with males having higher rates than females in 22
      sites. Over 60% of students reported having been exposed to secondhand smoke in
      public places in 23 of 39 sites. The majority of students recognized that they
      are role models in society, believed they should receive training on counseling
      patients to quit using tobacco, but few reported receiving any formal training.
      Tobacco control efforts must discourage tobacco use among health professionals,
      promote smoke free workplaces, and implement programs that train health
      professionals in effective cessation-counseling techniques.

PMID- 20054452
TI  - Epidemiological study of rickettsial infections in patients with
      hypertransaminemia in Madrid (Spain).
AB  - A retrospective analysis was performed to detect anti-rickettsial antibodies in
      the serum of patients with hypertransaminemia of unknown etiology, and in that of
      healthy members of the general population of Madrid (Spain). Among 143 patients
      16 (11.2%) were positive for anti-R. conorii IgG antibodies and 7% for R. typhi.
      PCR analysis was performed in patients with IgM antibodies. Among 143 healthy
      subjects from the general population, seven (4.9%) were positive for anti-R.
      conorii IgG antibodies, and 2.8% for R. typhi. These results show that anti
      rickettsial antibodies are more commonly detected in patients with
      hypertransaminemia than in healthy people.

PMID- 20054454
TI  - Specialist community nurses: a critical analysis of their role in the management
      of long-term conditions.
AB  - The aim of this narrative review is to identify strategies in use by specialist
      community and public health nurses in the prevention, care and management of
      individuals with long-term conditions, specifically chronic obstructive pulmonary
      disease (COPD) and musculoskeletal disorders. These conditions have been selected
      as they are highly prevalent; a burden on health services globally and a major
      public health issue. From a UK policy perspective, specialist community nurses
      have been placed at the forefront of taking a lead role in the coordination and
      delivery of more responsive services for individuals with long-term conditions;
      whether this has been an effective use of skills and resource is questionable. We
      systematically searched relevant databases between 1999-2009 to identify
      interventions used by specialist community nurses and critically appraised the
      studies. This review reports on impact and value of interventions used by
      specialist community nurses in the prevention and management of COPD and
      musculoskeletal conditions, and makes recommendations for improving services.

PMID- 20054455
TI  - Preventing and managing cardiometabolic risk: the logic for intervention.
AB  - Cardiometabolic risk (CMR), also known as metabolic syndrome or insulin
      resistance syndrome, comprises obesity (particularly central or abdominal
      obesity), high triglycerides, low HDL, elevated blood pressure, and elevated
      plasma glucose. Leading to death from diabetes, heart disease, and stroke, the
      root cause of CMR is inadequate physical activity, a Western diet identified
      primarily by low intake of fruits, vegetables, and whole grains, and high in
      saturated fat, as well as a number of yet-to-be-identified genetic factors. While
      the pathophysiological pathways related to CMR are complex, the universal need
      for adequate physical activity and a diet that emphasizes fruits and vegetables
      and whole grains, while minimizing food high in added sugars and saturated fat
      suggests that these behaviors are the appropriate focus of intervention.

PMID- 20054456
TI  - Vitamin D and calcium insufficiency-related chronic diseases: an emerging world
      wide public health problem.
AB  - Vitamin D and calcium insufficiencies are risk factors for multiple chronic
      diseases. Data from 46 recent studies from Europe, North America, South-East Asia
      and the South Pacific area clearly indicate that a low vitamin D status and
      inadequate calcium nutrition are highly prevalent in the general population (30
      80%), affecting both genders. The extent of insufficiencies is particularly high
      in older populations, and in some geographical areas, also in children and in
      young women of child-bearing age, in ethnic minorities and immigrants, as well as
      in people of low socio-economic status. Enrichment of cereal grain products with
      vitamin D and calcium would be a viable approach to increase consumption and
      improve health outcomes in the general population worldwide.

PMID- 20054457
TI  - Clients' experiences of a community based lifestyle modification program: a
      qualitative study.
AB  - There is little information about how clients attending lifestyle modification
      programs view the outcomes. This qualitative study examined the clients'
      experience of a community based lifestyle modification program in Hong Kong. Semi
      structured interviews were conducted with 25 clients attending the program.
      Clients perceived the program had positive impacts on their health and nutrition
      knowledge. They experienced frustration, negative emotion, lack of motivation,
      and pressure from others during the program. Working environment and lack of
      healthy food choices in restaurants were the major perceived environmental
      barriers for lifestyle modification. Clients valued nutritionists' capability of
      providing professional information and psychological support in the program. Our
      results suggest that nutritionist's capability of providing quality consultations
      and patient-centered care are important for empowering clients achieve lifestyle
      modification.

PMID- 20054458
TI  - Sustainability: environmental studies and public health.

PMID- 20054459
TI  - Food choices and coronary heart disease: a population based cohort study of rural
      Swedish men with 12 years of follow-up.
AB  - Coronary heart disease is associated with diet. Nutritional recommendations are
      frequently provided, but few long term studies on the effect of food choices on
      heart disease are available. We followed coronary heart disease morbidity and
      mortality in a cohort of rural men (N = 1,752) participating in a prospective
      observational study. Dietary choices were assessed at baseline with a 15-item
      food questionnaire. 138 men were hospitalized or deceased owing to coronary heart
      disease during the 12 year follow-up. Daily intake of fruit and vegetables was
      associated with a lower risk of coronary heart disease when combined with a high
      dairy fat consumption (odds ratio 0.39, 95% CI 0.21-0.73), but not when combined
      with a low dairy fat consumption (odds ratio 1.70, 95% CI 0.97-2.98). Choosing
      wholemeal bread or eating fish at least twice a week showed no association with
      the outcome.

PMID- 20054460
TI  - Assessing the effects of weather conditions on physical activity participation
      using objective measures.
AB  - Habitual physical activity is an important determinant of health, yet many people
      are considered to be inactive. Identification of the obstacles to greater
      participation is necessary for the development of strategies to overcome those
      obstacles. The weather has been identified as a perceived barrier to
      participation in physical activity, but exactly which adverse weather conditions
      are most important, and the extent to which they contribute to decreases in
      physical activity have rarely been quantified in populations. In the past decade,
      a small number of studies have used publicly available databases to examine the
      quantitative effects of weather (e.g., temperature, precipitation, wind) on
      physical activity in children, adolescents and adults. This review examines our
      historical, qualitative versus emerging, quantitative understanding of how
      specific weather conditions affect a population's activity.

PMID- 20054461
TI  - The relationship between odour annoyance scores and modelled ambient air
      pollution in Sarnia, "Chemical Valley", Ontario.
AB  - This study aimed at establishing the relationship between annoyance scores and
      modelled air pollution in "Chemical Valley", Sarnia, Ontario (Canada). Annoyance
      scores were taken from a community health survey (N = 774); and respondents'
      exposure to nitrogen dioxide (NO(2)) and sulphur dioxide (SO(2)) were estimated
      using land use regression (LUR) models. The associations were examined by
      univariate analysis while multivariate logistic regression was used to examine
      the determinants of odour annoyance. The results showed that odour annoyance was
      significantly correlated to modelled pollutants at the individual (NO(2), r =
      0.15; SO(2), r = 0.13) and census tract (NO(2), r = 0.56; SO(2), r = 0.67)
      levels. The exposure-response relationships show that residents of Sarnia react
      to very low pollution concentrations levels even if they are within the Ontario
      ambient air quality criteria. The study found that exposure to high NO(2) and
      SO(2) concentrations, gender, and perception of health effects were significant
      determinants of individual odour annoyance reporting. The observed association
      between odour annoyance and modelled ambient pollution suggest that individual
      and census tract level annoyance scores may serve as proxies for air quality in
      exposed communities because they capture the within area spatial variability of
      pollution. However, questionnaire-based odour annoyance scores need to be
      validated longitudinally and across different scales if they are to be adopted
      for use at the national level.

PMID- 20054462
TI  - Health and retirement in Europe.
AB  - We use discrete-time hazard models with internationally comparable data from the
      full eight waves of the European Community Household Panel (ECHP) to study the
      relationship between retirement and health in nine European countries. Our
      results provide new evidence of the relationship of health shocks to early
      retirement. The pattern of results across countries reflects international
      differences in the incentives created by social security systems.

PMID- 20054463
TI  - Validity of self-reported weight and height of adolescents, its impact on
      classification into BMI-categories and the association with weighing behaviour.
AB  - This paper investigated the validity of self-reported height and weight of
      adolescents for the diagnosis of underweight, overweight and obesity and the
      influence of weighing behaviour on the accuracy. A total of 982 adolescents
      reported their height, weight, weighing behaviour and eating patterns in a
      questionnaire. Afterwards, their height and weight were measured and their Body
      Mass Index (BMI)-categories were determined using age- and gender-specific BMI
      cut-off points. Both girls and boys underreported their weight, whilst height was
      overestimated by girls and underestimated by boys. Cohen's d indicated that these
      misreportings were in fact trivial. The prevalence of underweight was
      overestimated when using the self-reported BMI for classification, whilst the
      prevalence of overweight and obesity was underestimated. Gender and educational
      level influenced the accuracy of the adolescents' self-reported BMI. Weighing
      behaviour only positively influenced the accuracy of the self-reported weight and
      not height or BMI. In summary, adolescents' self-reported weight and height
      cannot replace measured values to determine their BMI-category, and thus the
      latter are highly recommended when investigating underweight, overweight and
      obesity in adolescents.

PMID- 20054464
TI  - Factors affecting use of preventive tests for cardiovascular risk among Greeks.
AB  - Data from a Greek national representative sample was used to investigate socio
      demographic, self-perceived health, and health risk factors that determine the
      use of cardiovascular preventive tests (blood pressure, cholesterol and blood
      glucose). Chi-square and logistic regression analyses were used (p < 0.05). Older
      age, marriage, regular family doctor and chronic diseases increased the
      likelihood of receiving preventive tests, whereas low education and alcohol
      consumption reduced the likelihood of having these tests. The effect of obesity
      varied. Interventions which improve the knowledge of the poorly educated and
      empower the preventive role of the physicians may redress the inequalities and
      improve the effectiveness of preventive services utilization.

PMID- 20054465
TI  - Formation energies of antiphase boundaries in GaAs and GaP: an ab Initio study.
AB  - Electronic and structural properties of antiphase boundaries in group III-V
      semiconductor compounds have been receiving increased attention due to the
      potential to integration of optically-active III-V heterostructures on silicon or
      germanium substrates. The formation energies of {110}, {111}, {112}, and {113}
      antiphase boundaries in GaAs and GaP were studied theoretically using a full
      potential linearized augmented plane-wave density-functional approach. Results of
      the study reveal that the stoichiometric {110} boundaries are the most
      energetically favorable in both compounds. The specific formation energy gamma of
      the remaining antiphase boundaries increases in the order of gamma({113})
      approximately gamma({112}) < gamma({111}), which suggests {113} and {112} as
      possible planes for faceting and annihilation of antiphase boundaries in GaAs and
      GaP.

PMID- 20054466
TI  - Effect of interface structure on mechanical properties of advanced composite
      materials.
AB  - This paper deals with the effect of interface structures on the mechanical
      properties of fiber reinforced composite materials. First, the background of
      research, development and applications on hybrid composite materials is
      introduced. Second, metal/polymer composite bonded structures are discussed.
      Then, the rationale is given for nanostructuring the interface in composite
      materials and structures by introducing nanoscale features such as nanopores and
      nanofibers. The effects of modifying matrices and nano-architecturing interfaces
      on the mechanical properties of nanocomposite materials are examined. A nonlinear
      damage model for characterizing the deformation behavior of polymeric
      nanocomposites is presented and the application of this model to carbon nanotube
      reinforced and reactive graphite nanotube-reinforced epoxy composite materials is
      shown.

PMID- 20054467
TI  - A review of computational methods in materials science: examples from shock-wave
      and polymer physics.
AB  - This review discusses several computational methods used on different length and
      time scales for the simulation of material behavior. First, the importance of
      physical modeling and its relation to computer simulation on multiscales is
      discussed. Then, computational methods used on different scales are shortly
      reviewed, before we focus on the molecular dynamics (MD) method. Here we survey
      in a tutorial-like fashion some key issues including several MD optimization
      techniques. Thereafter, computational examples for the capabilities of numerical
      simulations in materials research are discussed. We focus on recent results of
      shock wave simulations of a solid which are based on two different modeling
      approaches and we discuss their respective assets and drawbacks with a view to
      their application on multiscales. Then, the prospects of computer simulations on
      the molecular length scale using coarse-grained MD methods are covered by means
      of examples pertaining to complex topological polymer structures including star
      polymers, biomacromolecules such as polyelectrolytes and polymers with intrinsic
      stiffness. This review ends by highlighting new emerging interdisciplinary
      applications of computational methods in the field of medical engineering where
      the application of concepts of polymer physics and of shock waves to biological
      systems holds a lot of promise for improving medical applications such as
      extracorporeal shock wave lithotripsy or tumor treatment.

PMID- 20054468
TI  - Enzymatic reactions in near critical CO2: The effect of pressure on phenol
      removal by tyrosinase.
AB  - The use of enzymes in supercritical CO(2) (SCCO(2)) has received extensive
      attention in recent years. Biocatalysts have the advantage of substrate
      specificity and SCCO(2) offers several advantages over liquid solvents. This work
      deals with the utilization of SCCO(2) as a medium for the enzymatic removal of
      phenol from aqueous solutions using tyrosinase. Since the presence of oxygen is
      crucial for the enzyme-catalyzed oxidation, the substantial solvating power of
      SCCO(2) makes it a promising medium for such reactions. The conversion of phenol
      was higher at 10 MPa. Under near critical conditions (7 MPa, 35 degrees C), the
      addition of air at 5 x 10(5) Pa of pressure improved phenol removal.

PMID- 20054469
TI  - Identification of different donor-acceptor structures via Forster Resonance
      Energy Transfer (FRET) in quantum-dot-perylene bisimide assemblies.
AB  - Nanoassemblies are formed via self-assembly of ZnS capped CdSe quantum dots (QD)
      and perylene bisimide (PBI) dyes. Upon assembly formation the QD
      photoluminescence is quenched, as can be detected both via single particle
      detection and ensemble experiments in solution. Quenching has been assigned to
      FRET and NON-FRET processes. Analysis of FRET allows for a distinction between
      different geometries of the QD dye assemblies. Time-resolved single molecule
      spectroscopy reveals intrinsic fluctuations of the PBI fluorescence lifetime and
      spectrum, caused by rearrangement of the phenoxy side groups. The distribution of
      such molecular conformations and their changed dynamics upon assembly formation
      are discussed in the scope of FRET efficiency and surface ligand density.

PMID- 20054470
TI  - Investigations on the mechanical properties of conducting polymer coating
      substrate structures and their influencing factors.
AB  - This review covers recent advances and work on the microstructure features,
      mechanical properties and cracking processes of conducting polymer film/coating-
      substrate structures under different testing conditions. An attempt is made to
      characterize and quantify the relationships between mechanical properties and
      microstructure features. In addition, the film cracking mechanism on the micro
      scale and some influencing factors that play a significant role in the service of
      the film-substrate structure are presented. These investigations cover the
      conducting polymer film/coating nucleation process, microstructure-fracture
      characterization, translation of brittle-ductile fractures, and cracking
      processes near the largest inherent macromolecule defects under thermal
      mechanical loadings, and were carried out using in situ scanning electron
      microscopy (SEM) observations, as a novel method for evaluation of interface
      strength and critical failure stress.

PMID- 20054471
TI  - Microwave effect for glycosylation promoted by solid super acid in supercritical
      carbon dioxide.
AB  - The effects of microwave irradiation (2.45 GHz, 200 W) on glycosylation promoted
      by a solid super acid in supercritical carbon dioxide was investigated with
      particular attention paid to the structure of the acceptor substrate. Because of
      the symmetrical structure and high diffusive property of supercritical carbon
      dioxide, microwave irradiation did not alter the temperature of the reaction
      solution, but enhanced reaction yield when aliphatic acceptors are employed.
      Interestingly, the use of a phenolic acceptor under the same reaction conditions
      did not show these promoting effects due to microwave irradiation. In the case of
      aliphatic diol acceptors, the yield seemed to be dependent on the symmetrical
      properties of the acceptors. The results suggest that microwave irradiation do
      not affect the reactivity of the donor nor promoter independently. We conclude
      that the effect of acceptor structure on glycosylation yield is due to electric
      delocalization of hydroxyl group and dielectrically symmetric structure of whole
      molecule.

PMID- 20054472
TI  - On the physical meaning of the isothermal titration calorimetry measurements in
      calorimeters with full cells.
AB  - We have performed a detailed study of the thermodynamics of the titration process
      in an isothermal titration calorimeter with full cells. We show that the
      relationship between the enthalpy and the heat measured is better described in
      terms of the equation Delta H = W(inj) + Q (where W(inj) is the work necessary to
      carry out the titration) than in terms of DeltaH = Q. Moreover, we show that the
      heat of interaction between two components is related to the partial enthalpy of
      interaction at infinite dilution of the titrant component, as well as to its
      partial volume of interaction at infinite dilution.

PMID- 20054474
TI  - Recent progress of flower colour modification by biotechnology.
AB  - Genetically-modified, colour-altered varieties of the important cut-flower crop
      carnation have now been commercially available for nearly ten years. In this
      review we describe the manipulation of the anthocyanin biosynthesis pathway that
      has lead to the development of these varieties and how similar manipulations have
      been successfully applied to both pot plants and another cut-flower species, the
      rose. From this experience it is clear that down- and up-regulation of the
      flavonoid and anthocyanin pathway is both possible and predictable. The major
      commercial benefit of the application of this technology has so far been the
      development of novel flower colours through the development of transgenic
      varieties that produce, uniquely for the target species, anthocyanins derived
      from delphinidin. These anthocyanins are ubiquitous in nature, and occur in both
      ornamental plants and common food plants. Through the extensive regulatory
      approval processes that must occur for the commercialization of genetically
      modified organisms, we have accumulated considerable experimental and trial data
      to show the accumulation of delphinidin based anthocyanins in the transgenic
      plants poses no environmental or health risk.

PMID- 20054473
TI  - The hunt for natural skin whitening agents.
AB  - Skin whitening products are commercially available for cosmetic purposes in order
      to obtain a lighter skin appearance. They are also utilized for clinical
      treatment of pigmentary disorders such as melasma or postinflammatory
      hyperpigmentation. Whitening agents act at various levels of melanin production
      in the skin. Many of them are known as competitive inhibitors of tyrosinase, the
      key enzyme in melanogenesis. Others inhibit the maturation of this enzyme or the
      transport of pigment granules (melanosomes) from melanocytes to surrounding
      keratinocytes. In this review we present an overview of (natural) whitening
      products that may decrease skin pigmentation by their interference with the
      pigmentary processes.

PMID- 20054475
TI  - Effects of genetic, pre- and post-harvest factors on phenolic content and
      antioxidant capacity of white asparagus spears.
AB  - The effects of genetic, pre-harvest (season of harvest, spear diameter, spear
      portion and spear tip color) and post-harvest factors (storage and domestic
      preparation practices, e.g., peeling and cooking) on total phenolic, flavonoid
      and ascorbic acid content of white asparagus spears and their correlation with
      antioxidant capacity (DPPH and FRAP) were studied. Results showed that genetic
      material was important for the total phenolic content but not season of harvest,
      spear diameter or storage. Violet spear tips and apical spear portions showed the
      largest amount of total phenolics. Peeling did not affect total phenolics in
      fresh asparagus, whereas it reduced their content in stored asparagus, while
      cooking resulted in an increase in both fresh and stored asparagus. However, the
      soluble extract of total phenolics and flavonoids were minor and the missing
      significance of phenolics and flavonoids in antioxidant capacity of white
      asparagus spears depends on these small amounts.

PMID- 20054476
TI  - A study of the crystallization, melting, and foaming behaviors of polylactic acid
      in compressed CO2.
AB  - The crystallization and melting behaviors of linear polylactic acid (PLA) treated
      by compressed CO(2) was investigated. The isothermal crystallization test
      indicated that while PLA exhibited very low crystallization kinetics under
      atmospheric pressure, CO(2) exposure significantly increased PLA's
      crystallization rate; a high crystallinity of 16.5% was achieved after CO(2)
      treatment for only 1 min at 100 degrees C and 6.89 MPa. One melting peak could be
      found in the DSC curve, and this exhibited a slight dependency on treatment
      times, temperatures, and pressures. PLA samples tended to foam during the gas
      release process, and a foaming window as a function of time and temperature was
      established. Based on the foaming window, crystallinity, and cell morphology, it
      was found that foaming clearly reduced the needed time for PLA's crystallization
      equilibrium.

PMID- 20054477
TI  - Binding of natural and synthetic polyphenols to human dihydrofolate reductase.
AB  - Dihydrofolate reductase (DHFR) is the subject of intensive investigation since it
      appears to be the primary target enzyme for antifolate drugs. Fluorescence
      quenching experiments show that the ester bond-containing tea polyphenols (-)
      epigallocatechin gallate (EGCG) and (-)-epicatechin gallate (ECG) are potent
      inhibitors of DHFR with dissociation constants (K(D))of 0.9 and 1.8 microM,
      respectively, while polyphenols lacking the ester bound gallate moiety [e.g., (-)
      epigallocatechin (EGC) and (-)-epicatechin (EC)] did not bind to this enzyme. To
      avoid stability and bioavailability problems associated with tea catechins we
      synthesized a methylated derivative of ECG (3-O-(3,4,5-trimethoxybenzoyl)-(-)
      epicatechin; TMECG), which effectively binds to DHFR (K(D) = 2.1 microM). In
      alkaline solution, TMECG generates a stable quinone methide product that strongly
      binds to the enzyme with a K(D) of 8.2 nM. Quercetin glucuronides also bind to
      DHFR but its effective binding was highly dependent of the sugar residue, with
      quercetin-3-xyloside being the stronger inhibitor of the enzyme with a K(D) of
      0.6 microM. The finding that natural polyphenols are good inhibitors of human
      DHFR could explain the epidemiological data on their prophylactic effects for
      certain forms of cancer and open a possibility for the use of natural and
      synthetic polyphenols in cancer chemotherapy.

PMID- 20054479
TI  - The study of the inhibition of the recombinant TACE prodomain to endotoxemia in
      mice.
AB  - OBJECTIVE: To demonstrate the inhibitory function of the prodomain of tumor
      necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) on TACE activity and
      to develop an approach to interfere with inflammation processes. METHODS: The
      cDNA encoding the full-length ectodomain (T1300) and prodomain (T591) of TACE
      were amplified by RT-PCR. The expression plasmids (pET-28a (+)-T1300 and pET-28a
      (+)-T591) were constructed and transformed into E. coli BL21. After Ni(2+)-NTA
      resin affinity chromatography, the recombinant T591 protein was obtained and
      assayed. In order to detect its inhibiton of TACE activity, the mice in the LPS
      induced endotoxemia model group were treated with the recombinant TACE prodomain
      protein prior to the injection of LPS. Murine peritoneal macrophages were
      isolated from mice abdominal cavity for FCM and the liver, kidney and lung were
      removed for traditionally histopathology sectioning. RESULTS: The FCM results
      showed that the recombinant prodomain protein decreased the release of the sTNF
      alpha, which mediated the accumulation of TNF-alpha on the surface of macrophage
      cells. HE staining proved that the recombinant protein can decrease the
      inflammatory response in internal organs of endotoxaemia mice. CONCLUSIONS: The
      recombinant prodomain of TACE has the ability to inhibit sTNF-alpha release,
      which indicates that prodomain is an effective antagonist of TACE and might be
      useful in the molecular design of anti-inflammatory drugs.

PMID- 20054478
TI  - Cell culture on MEMS platforms: a review.
AB  - Microfabricated systems provide an excellent platform for the culture of cells,
      and are an extremely useful tool for the investigation of cellular responses to
      various stimuli. Advantages offered over traditional methods include cost
      effectiveness, controllability, low volume, high resolution, and sensitivity.
      Both biocompatible and bio-incompatible materials have been developed for use in
      these applications. Biocompatible materials such as PMMA or PLGA can be used
      directly for cell culture. However, for bio-incompatible materials such as
      silicon or PDMS, additional steps need to be taken to render these materials more
      suitable for cell adhesion and maintenance. This review describes multiple
      surface modification strategies to improve the biocompatibility of MEMS
      materials. Basic concepts of cell-biomaterial interactions, such as protein
      adsorption and cell adhesion are covered. Finally, the applications of these MEMS
      materials in Tissue Engineering are presented.

PMID- 20054480
TI  - Sharp phylogeographic breaks and patterns of genealogical concordance in the
      brine shrimp Artemia franciscana.
AB  - Genealogical concordance is a critical overlay of all phylogenetic analyses,
      irrespective of taxonomic level. To assess such patterns of congruence we have
      compiled and derived sequence data for two mitochondrial (16S rRNA, COI) and two
      nuclear (ITS1, p26) markers in 14 American populations of the hypersaline
      branchiopod Artemia franciscana. Cladistic analysis revealed three reciprocally
      monophyletic mitochondrial clades. For nuclear DNA, incomplete lineage sorting
      was evident presumably as a result of slower coalescence or male-mediated
      dispersal. Our findings capture the genealogical interval between gene splitting
      and population divergence. In this sense, strong indications are provided in
      favour of a superspecies status and ongoing speciation in A. franciscana.

PMID- 20054481
TI  - Immune response among patients exposed to molds.
AB  - Macrocyclic trichothecenes, mycotoxins produced by Stachybotrys chartarum, have
      been implicated in adverse reactions in individuals exposed to mold-contaminated
      environments. Cellular and humoral immune responses and the presence of
      trichothecenes were evaluated in patients with mold-related health complaints.
      Patients underwent history, physical examination, skin prick/puncture tests with
      mold extracts, immunological evaluations and their sera were analyzed for
      trichothecenes. T-cell proliferation, macrocyclic trichothecenes, and mold
      specific IgG and IgA levels were not significantly different than controls;
      however 70% of the patients had positive skin tests to molds. Thus, IgE mediated
      or other non-immune mechanisms could be the cause of their symptoms.

PMID- 20054482
TI  - Chelation of Cu(II), Zn(II), and Fe(II) by tannin constituents of selected edible
      nuts.
AB  - The tannin fractions isolated from hazelnuts, walnuts and almonds were
      characterised by colorimetric assays and by an SE-HPLC technique. The
      complexation of Cu(II) and Zn(II) was determined by the reaction with
      tetramethylmurexide, whereas for Fe(II), ferrozine was employed. The walnut
      tannins exhibited a significantly weaker reaction with the vanillin/HCl reagent
      than hazelnut and almond tannins, but the protein precipitation capacity of the
      walnut fraction was high. The SE-HPLC chromatogram of the tannin fraction from
      hazelnuts revealed the presence of oligomers with higher molecular weights
      compared to that of almonds. Copper ions were most effectively chelated by the
      constituents of the tannin fractions of hazelnuts, walnuts and almonds. At a 0.2
      mg/assay addition level, the walnut tannins complexed almost 100% Cu(II). The
      Fe(II) complexation capacities of the tannin fractions of walnuts and hazelnuts
      were weaker in comparison to that of the almond tannin fraction, which at a 2.5
      mg/assay addition level, bound Fe(II) by approximately 90%. The capacity to
      chelate Zn(II) was quite varied for the different nut tannin fractions: almond
      tannins bound as much as 84% Zn(II), whereas the value for walnut tannins was
      only 8.7%; and for hazelnut tannins, no Zn(II) chelation took place at the levels
      tested.

PMID- 20054483
TI  - Contributions of the C-terminal helix to the structural stability of a
      hyperthermophilic Fe-superoxide dismutase (TcSOD).
AB  - Hyperthermophilic superoxide dismutases (SODs) are of particular interest due to
      their potential industrial importance and scientific merit in studying the
      molecular mechanisms of protein folding and stability. Compared to the mesophilic
      SODs, the hyperthermostable Fe-SODs (TcSOD and ApSOD) have an extended C-terminal
      helix, which forms an additional ion-pairing network. In this research, the role
      of the extended C-terminus in the structural stability of TcSOD was studied by
      investigating the properties of two deletion mutants. The results indicated that
      the ion-pairing network at the C-terminus had limited contributions to the
      stability of TcSOD against heat- and GdnHCl-induced inactivation. The intactness
      of the C-terminal helix had dissimilar impact on the two stages of TcSOD
      unfolding induced by guanidinium chloride. The mutations slightly decreased the
      Gibbs free energy of the dissociation of the tetrameric enzymes, while greatly
      affected the stability of the molten globule-like intermediate. These results
      suggested that the additional ion-pairing network mainly enhanced the structural
      stability of TcSOD by stabilizing the monomers.

PMID- 20054484
TI  - Antioxidant activity of a red lentil extract and its fractions.
AB  - Phenolic compounds were extracted from red lentil seeds using 80% (v/v) aqueous
      acetone. The crude extract was applied to a Sephadex LH-20 column. Fraction 1,
      consisting of sugars and low-molecular-weight phenolics, was eluted from the
      column by ethanol. Fraction 2, consisting of tannins, was obtained using acetone
      water (1:1; v/v) as the mobile phase. Phenolic compounds present in the crude
      extract and its fractions demonstrated antioxidant and antiradical activities as
      revealed from studies using a beta-carotene-linoleate model system, the total
      antioxidant activity (TAA) method, the DPPH radical-scavenging activity assay,
      and a reducing power evaluation. Results of these assays showed the highest
      values when tannins (fraction 2) were tested. For instance, the TAA of the tannin
      fraction was 5.85 micromol Trolox eq./mg, whereas the crude extract and fraction
      1 showed 0.68 and 0.33 micromol Trolox eq./mg, respectively. The content of total
      phenolics in fraction 2 was the highest (290 mg/g); the tannin content,
      determined using the vanillin method and expressed as absorbance units at 500 nm
      per 1 g, was 129. There were 24 compounds identified in the crude extract using
      an HPLC-ESI-MS method: quercetin diglycoside, catechin, digallate procyanidin,
      and p-hydroxybenzoic were the dominant phenolics in the extract.

PMID- 20054485
TI  - Altered gene expression in cerulein-stimulated pancreatic acinar cells:
      pathologic mechanism of acute pancreatitis.
AB  - Acute pancreatitis is a multifactorial disease associated with the premature
      activation of digestive enzymes. The genes expressed in pancreatic acinar cells
      determine the severity of the disease. The present study determined the
      differentially expressed genes in pancreatic acinar cells treated with cerulein
      as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were
      stimulated with 10(-8) M cerulein for 4 h, and genes with altered expression were
      identified using a cDNA microarray for 4,000 rat genes and validated by real-time
      PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin,
      guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced
      protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a
      2.5-fold or higher decreases in expression. Real-time PCR analysis showed time
      dependent alterations of these genes. Using commercially available antibodies
      specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a
      time-dependent increase in these proteins were observed by Western blotting.
      Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement,
      enzyme activity, and secretion may be underlying mechanisms of acute
      pancreatitis.

PMID- 20054486
TI  - Hexane-Soluble Fraction of the Common Fig, Ficus carica, Inhibits Osteoclast
      Differentiation in Murine Bone Marrow-Derived Macrophages and RAW 264.7 Cells.
AB  - Osteoclasts, derived from multipotent myeloid progenitor cells, play homeostatic
      roles in skeletal modeling and remodeling, but may also destroy bone in
      pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclast
      development depends critically on a differentiation factor, the receptor
      activator of NF-kappaB ligand (RANKL). In this study, we found that the hexane
      soluble fraction of the common fig Ficus carica (HF6-FC) is a potent inhibitor of
      osteoclastogenesis in RANKL-stimulated RAW264.7 cells and in bone marrow-derived
      macrophages (BMMs). HF6-FC exerts its inhibitory effects by suppression of p38
      and NF-kappaB but activation of ERK. In addition, HF6-FC significantly decreased
      the expression of NFATc1 and c-Fos, the master regulator of osteoclast
      differentiation. The data indicate that components of HF6-FC may have therapeutic
      effects on bone-destructive processes such as osteoporosis, rheumatoid arthritis,
      and periodontal bone resorption.

PMID- 20054487
TI  - The Antinociceptive Effect of Sigma-1 Receptor Antagonist, BD1047, in a Capsaicin
      Induced Headache Model in Rats.
AB  - Intracranial headaches, including migraines, are mediated by nociceptive
      activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms
      are poorly understood. We previously demonstrated that selective blockage of
      spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in
      several types of pain models. This study evaluates whether the Sig-1R antagonist
      (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator)
      induced headache models in rats. Intracisternal infusion of capsaicin evoked pain
      behavior (face grooming), which was significantly attenuated by BD1047
      pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like
      immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent
      manner. Moreover, capsaicin-induced phosphorylation of N-methyl-D-aspartate
      receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results
      indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive
      activation of the TNC in the capsaicin-induced headache animal model.

PMID- 20054488
TI  - Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the
      Upregulation of Catalase.
AB  - The role of apurinic/apyrimidinic endonuclease1/redox factor-1 (Ref-1) on the
      lead (Pb)-induced cellular response was investigated in the cultured endothelial
      cells. Pb caused progressive cellular death in endothelial cells, which occurred
      in a concentration- and time-dependent manner. However, Ref-1 overexpression with
      AdRef-1 significantly inhibited Pb-induced cell death in the endothelial cells.
      Also the overexpression of Ref-1 significantly suppressed Pb-induced superoxide
      and hydrogen peroxide elevation in the endothelial cells. Pb exposure induced the
      downregulation of catalase, it was inhibited by the Ref-1 overexpression in the
      endothelial cells. Taken together, our data suggests that the overexpression of
      Ref-1 inhibited Pb-induced cell death via the upregulation of catalase in the
      cultured endothelial cells.

PMID- 20054489
TI  - Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca Channels
      in Neonatal Rat Ventricular Cardiomyocytes.
AB  - A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including
      cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the
      highest CV risk such as congestive heart failure, which resulted commonly from
      the impaired cardiac pumping due to a disrupted excitation-contraction (E-C)
      coupling. We investigated the effects of diclofenac on the L-type calcium
      channels which are essential to the E-C coupling at the level of single
      ventricular myocytes isolated from neonatal rat heart, using the whole-cell
      voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and
      ibuprofen, significantly reduced inward whole cell currents. At concentrations
      higher than 3 microM, diclofenac inhibited reversibly the Na(+) current and did
      irreversibly the L-type Ca(2+) channels-mediated inward current (IC(50)=12.89+/
      0.43 microM) in a dose-dependent manner. However, nifedipine, a well-known L-type
      channel blocker, effectively inhibited the L-type Ca(2+) currents but not the
      Na(+) current. Our finding may explain that diclofenac causes the CV risk by the
      inhibition of L-type Ca(2+) channel, leading to the impairment of E-C coupling in
      cardiac myocytes.

PMID- 20054490
TI  - Electrically-evoked Neural Activities of rd1 Mice Retinal Ganglion Cells by
      Repetitive Pulse Stimulation.
AB  - For successful visual perception by visual prosthesis using electrical
      stimulation, it is essential to develop an effective stimulation strategy based
      on understanding of retinal ganglion cell (RGC) responses to electrical
      stimulation. We studied RGC responses to repetitive electrical stimulation pulses
      to develop a stimulation strategy using stimulation pulse frequency modulation.
      Retinal patches of photoreceptor-degenerated retinas from rd1 mice were attached
      to a planar multi-electrode array (MEA) and RGC spike trains responding to
      electrical stimulation pulse trains with various pulse frequencies were observed.
      RGC responses were strongly dependent on inter-pulse interval when it was varied
      from 500 to 10 ms. Although the evoked spikes were suppressed with increasing
      pulse rate, the number of evoked spikes were >60% of the maximal responses when
      the inter-pulse intervals exceeded 100 ms. Based on this, we investigated the
      modulation of evoked RGC firing rates while increasing the pulse frequency from 1
      to 10 pulses per second (or Hz) to deduce the optimal pulse frequency range for
      modulation of RGC response strength. RGC response strength monotonically and
      linearly increased within the stimulation frequency of 1~9 Hz. The results
      suggest that the evoked neural activities of RGCs in degenerated retina can be
      reliably controlled by pulse frequency modulation, and may be used as a
      stimulation strategy for visual neural prosthesis.

PMID- 20054491
TI  - Overexpression of AMPKalpha1 Ameliorates Fatty Liver in Hyperlipidemic Diabetic
      Rats.
AB  - 5'-AMP-activated protein kinase (AMPK) is a heterotrimeric complex consisting of
      a catalytic (alpha) and two regulatory (beta and gamma) subunits. Two isoforms
      are known for catalytic subunit (alpha1, alpha2) and are encoded by different
      genes. To assess the metabolic effects of AMPKalpha1, we examined the effects of
      overexpression of adenoviral-mediated AMPKalpha1 in hyperlipidemic type 2
      diabetic rats. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an
      established animal model of type 2 diabetes that exhibits chronic and slowly
      progressive hyperglycemia and hyperlipidemia. Thirty five-week-old overt type 2
      diabetic rats (n=10) were administered intravenously with Ad.AMPKalpha1. AMPK
      activity was measured by phosphorylation of acetyl CoA carboxlyase (ACC). To
      investigate the changes of gene expression related glucose and lipid metabolism,
      quantitative real-time PCR was performed with liver tissues. Overexpression of
      AMPKalpha1 showed that blood glucose concentration was decreased but that glucose
      tolerance was not completely recovered on 7th day after treatment. Plasma
      triglyceride concentration was decreased slightly, and hepatic triglyceride
      content was markedly reduced by decreasing expression of hepatic lipogenic genes.
      Overexpression of AMPKalpha1 markedly improved hepatic steatosis and it may have
      effective role for improving hepatic lipid metabolism in hyperlipidemic state.

PMID- 20054492
TI  - Type II and III Taste Bud Cells Preferentially Expressed Kainate Glutamate
      Receptors in Rats.
AB  - Glutamate-induced cobalt uptake reveals that non-NMDA glutamate receptors (GluRs)
      are present in rat taste bud cells. Previous studies involving glutamate induced
      cobalt staining suggest this uptake mainly occurs via kainate type GluRs. It is
      not known which of the 4 types of taste bud cells express subunits of kainate
      GluR. Circumvallate and foliate papillae of Sprague-Dawley rats (45~60 days old)
      were used to search for the mRNAs of subunits of non-NMDA GluRs using RT-PCR with
      specific primers for GluR1-7, KA1 and KA2. We also performed RT-PCR for GluR5,
      KA1, PLCbeta2, and NCAM/SNAP 25 in isolated single cells from taste buds. Taste
      epithelium, including circumvallate or foliate papilla, express mRNAs of GluR5
      and KA1. However, non-taste tongue epithelium expresses no subunits of non-NMDA
      GluRs. Isolated single cell RT-PCR reveals that the mRNAs of GluR5 and KA1 are
      preferentially expressed in Type II and Type III cells over Type I cells.

PMID- 20054493
TI  - Nitric oxide modulation of GABAergic synaptic transmission in mechanically
      isolated rat auditory cortical neurons.
AB  - The auditory cortex (A1) encodes the acquired significance of sound for the
      perception and interpretation of sound. Nitric oxide (NO) is a gas molecule with
      free radical properties that functions as a transmitter molecule and can alter
      neural activity without direct synaptic connections. We used whole-cell
      recordings under voltage clamp to investigate the effect of NO on spontaneous
      GABAergic synaptic transmission in mechanically isolated rat auditory cortical
      neurons preserving functional presynaptic nerve terminals. GABAergic spontaneous
      inhibitory postsynaptic currents (sIPSCs) in the A1 were completely blocked by
      bicuculline. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reduced the
      GABAergic sIPSC frequency without affecting the mean current amplitude. The SNAP
      induced inhibition of sIPSC frequency was mimicked by 8-bromoguanosine cyclic
      3',5'-monophosphate, a membrane permeable cyclic-GMP analogue, and blocked by 2
      (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific NO
      scavenger. Blockade of presynaptic K(+) channels by 4-aminopyridine, a K(+)
      channel blocker, increased the frequencies of GABAergic sIPSCs, but did not
      affect the inhibitory effects of SNAP. However, blocking of presynaptic Ca(2+)
      channels by Cd(2+), a general voltage-dependent Ca(2+) channel blocker, decreased
      the frequencies of GABAergic sIPSCs, and blocked SNAP-induced reduction of sIPSC
      frequency. These findings suggest that NO inhibits spontaneous GABA release by
      activation of cGMP-dependent signaling and inhibition of presynaptic Ca(2+)
      channels in the presynaptic nerve terminals of A1 neurons.

PMID- 20054494
TI  - Intraocular injection of muscimol induces illusory motion reversal in goldfish.
AB  - Induced activation of the gamma-aminobutyric acid(A) (GABA(A)) receptor in the
      retina of goldfish caused the fish to rotate in the opposite direction to that of
      the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a
      GABA(A) receptor agonist, modified OMR in a concentration-dependent manner. The
      GABA(B) receptor agonist baclofen and GABA(C) receptor agonist CACA did not
      affect OMR. The observed modifications in OMR included decreased anterograde
      rotation (0.01~0.03 microM), coexistence of retrograde rotation and decreased
      anterograde rotation (0.1~30 microM) and only retrograde rotation (100 microM~1
      mM). In contrast, the GABA(A) receptor antagonist bicuculline blocked
      muscimolinduced retrograde rotation. Based on these results, we inferred that the
      coding inducing retrograde movement of the goldfish retina is essentially
      associated with the GABA(A) receptor-related visual pathway. Furthermore, from
      our novel approach using observations of goldfish behavior the induced discrete
      snapshot duration was approximately 573 ms when the fish were under the influence
      of muscimol.

PMID- 20054495
TI  - Rifampicin Inhibits the LPS-induced Expression of Toll-like Receptor 2 via the
      Suppression of NF-kappaB DNA-binding Activity in RAW 264.7 Cells.
AB  - Rifampicin is a macrocyclic antibiotic which is used extensively for treatment
      against Mycobacterium tuberculosis and other mycobacterial infections. Recently,
      a number of studies have focused on the immune-regulatory effects of rifampicin.
      Therefore, we hypothesized that rifampicin may influence the TLR2 expression in
      LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin
      suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2
      expression coincided with decreased production of TNF-alpha. Since NF-kappaB is a
      major transcription factor that regulates genes for TLR2 and TNF-alpha, we
      examined the effect of rifampicin on the LPS-induced NF-kappaB activation.
      Rifampicin inhibited NF-kappaB DNA-binding activity in LPS-activated RAW 264.7
      cells, while it did not affect IKKalpha/beta activity. However, rifampicin
      slightly inhibited the nuclear translocation of NF-kappaB p65. In addition,
      rifampicin increased physical interaction between pregnane X receptor, a receptor
      for rifampicin, and NF-kappaB p65, suggesting pregnane X receptor interferes with
      NF-kappaB binding to DNA. Taken together, our results demonstrate that rifampicin
      inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF
      kappaB DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest
      that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-kappaB
      DNA-binding activity may be a novel mechanism of the immune-suppressive effects
      of rifampicin.

PMID- 20054496
TI  - Knockdown of RCAN1.4 Increases Susceptibility to FAS-mediated and DNA-damage
      induced Apoptosis by Upregulation of p53 Expression.
AB  - Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1)
      gene in the modulation of cell survival under stress, little is known about its
      role in death-inducing signal pathways. In this study, we addressed the effects
      of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation
      of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in
      enhanced Fas- and etoposide-induced apoptosis, which was associated with
      increased expression and translocation of Bax to mitochondria. Our results
      suggest that enhanced expression and activation of p53 was responsible for the
      upregulation of Bax and the increased sensitivity to apoptosis, which could be
      reversed by p53 knockdown. To explain the observed upregulation of p53, we
      propose a downregulation of the ubiquitin ligase HDM2, probably translationally.
      These findings show the importance of appropriate RCAN1.4 expression in the
      modulation of cell survival and reveal a link between RCAN1.4 and p53.

PMID- 20054497
TI  - p38 MAPK Participates in Muscle-Specific RING Finger 1-Mediated Atrophy in Cast
      Immobilized Rat Gastrocnemius Muscle.
AB  - Skeletal muscle atrophy is a common phenomenon during the prolonged muscle disuse
      caused by cast immobilization, extended aging states, bed rest, space flight, or
      other factors. However, the cellular mechanisms of the atrophic process are
      poorly understood. In this study, we investigated the involvement of mitogen
      activated protein kinase (MAPK) in the expression of muscle-specific RING finger
      1 (MuRF1) during atrophy of the rat gastrocnemius muscle. Histological analysis
      revealed that cast immobilization induced the atrophy of the gastrocnemius
      muscle, with diminution of muscle weight and cross-sectional area after 14 days.
      Cast immobilization significantly elevated the expression of MuRF1 and the
      phosphorylation of p38 MAPK. The starvation of L6 rat skeletal myoblasts under
      serum-free conditions induced the phosphorylation of p38 MAPK and the
      characteristics typical of cast-immobilized gastrocnemius muscle. The expression
      of MuRF1 was also elevated in serum-starved L6 myoblasts, but was significantly
      attenuated by SB203580, an inhibitor of p38 MAPK. Changes in the sizes of L6
      myoblasts in response to starvation were also reversed by their transfection with
      MuRF1 small interfering RNA or treatment with SB203580. From these results, we
      suggest that the expression of MuRF1 in cast-immobilized atrophy is regulated by
      p38 MAPK in rat gastrocnemius muscles.

PMID- 20054498
TI  - Efficient management design for swimming exercise treatment.
AB  - Exercise-mediated physical treatment has attracted much recent interest. In
      particular, swimming is a representative exercise treatment method recommended
      for patients experiencing muscular and cardiovascular diseases. The present study
      sought to design a swimming-based exercise treatment management system. A survey
      questionnaire was completed by participants to assess the prevalence of muscular
      and cardiovascular diseases among adult males and females participating in
      swimming programs at sport centers in metropolitan regions of country. Using the
      Fuzzy Analytic Hierarchy Process (AHP) technique, weighted values of indices were
      determined, to maximize participant clarity. A patient management system model
      was devised using information technology. The favorable results are evidence of
      the validity of this approach. Additionally, the swimming-based exercise
      management system can be supplemented together with analyses of weighted values
      considering connectivity between established indices.

PMID- 20054499
TI  - Relaxation patterns of human gastric corporal smooth muscle by cyclic nucleotides
      producing agents.
AB  - To elucidate the mechanism of cyclic nucleotides, such as adenosine 3',5'-cyclic
      monophosphate (cAMP) and guanosine 3',5' -cyclic monophosphate (cGMP), in the
      regulation of human gastric motility, we examined the effects of forskolin (FSK),
      isoproterenol (ISO) and sodium nitroprusside (SNP) on the spontaneous, high K(+)
      and acetylcholine (ACh)-induced contractions of corporal circular smooth muscle
      in human stomach. Gastric circular smooth muscle showed regular spontaneous
      contraction, and FSK, ISO and SNP inhibited its phasic contraction and basal tone
      in a concentration-dependent manner. High K(+) (50 mM) produced sustained tonic
      contraction, and ACh (10 microM) produced initial transient contraction followed
      by later sustained tonic contraction with superimposed phasic contractions. FSK,
      ISO and SNP inhibited high K(+)-induced tonic contraction and also ACh-induced
      phasic and tonic contraction in a reversible manner. Nifedipine (1 microM),
      inhibitor of voltage-dependent L-type calcium current (VDCC(L)), almost abolished
      ACh-induced phasic contractions. These findings suggest that FSK, ISO and SNP,
      which are known cyclic nucleotide stimulators, inhibit smooth muscle contraction
      in human stomach partly via inhibition of VDCC(L).

PMID- 20054500
TI  - Cytotoxic Activity and Three-Dimensional Quantitative Structure Activity
      Relationship of 2-Aryl-1,8-naphthyridin-4-ones.
AB  - A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously
      synthesized in our laboratory, were evaluated for their in vitro cytotoxic
      activity against human lung cancer A549 and human renal cancer Caki-2 cells using
      MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than
      colchicine against both tumor cell lines, and compound 13 exhibited the most
      potent activity with IC(50) values of 2.3 and 13.4 microM, respectively. Three
      dimensional quantitative structure activity relationship (3D-QSAR) studies of
      comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained
      with q(2) values of 0.869 and 0.872 and r(2) (ncv) values of 0.983 and 0.993 for
      CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA
      models could be reliably used in the design of novel cytotoxic agents.

PMID- 20054501
TI  - Polyphenols of Rubus coreanum Inhibit Catecholamine Secretion from the Perfused
      Adrenal Medulla of SHRs.
AB  - The present study was attempted to investigate whether polyphenolic compounds
      isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect
      the release of catecholamines (CA) from the isolated perfused adrenal medulla of
      the spontaneously hypertensive rats (SHRs), and to establish its mechanism of
      action. PCRC (20~180 microg/ml) perfused into an adrenal vein for 90 min
      relatively dose-dependently inhibited the CA secretory responses to ACh (5.32
      mM), high K(+) (56 mM), DMPP (100 microM) and McN-A-343 (100 microM). PCRC itself
      did not affect basal CA secretion (data not shown). Also, in the presence of PCRC
      (60 microg/ml), the CA secretory responses to veratridine (a selective Na(+)
      channel activator (10 microM), Bay-K-8644 (a L-type dihydropyridine Ca(2+)
      channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca(2+) 
      ATPase inhibitor, 10 microM) were significantly reduced, respectively. In the
      simultaneous presence of PCRC (60 microg/ml) and L-NAME (an inhibitor of NO
      synthase, 30 microM), the inhibitory responses of PCRC on the CA secretion evoked
      by ACh, high K(+), DMPP, and Bay-K-8644 were considerably recovered to the extent
      of the corresponding control secretion compared with that of PCRC-treatment
      alone. The level of NO released from adrenal medulla after the treatment of PCRC
      (60 microg/ml) was greatly elevated compared with the corresponding basal level.
      Taken together, these results demonstrate that PCRC inhibits the CA secretion
      from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of
      cholinergic receptors as well as by direct membrane-depolarization. It seems that
      this inhibitory effect of PCRC is mediated by blocking the influx of calcium and
      sodium into the adrenal medullary chromaffin cells of the SHRs as well as by
      inhibition of Ca(2+) release from the cytoplasmic calcium store at least partly
      through the increased NO production due to the activation of NO synthase.

PMID- 20054502
TI  - Recommendations of the International Medical Informatics Association (IMIA) on
      Education in Biomedical and Health Informatics. First Revision.
AB  - Objective: The International Medical Informatics Association (IMIA) agreed on
      revising the existing international recommendations in health informatics/medical
      informatics education. These should help to establish courses, course tracks or
      even complete programs in this field, to further develop existing educational
      activities in the various nations and to support international initiatives
      concerning education in biomedical and health informatics (BMHI), particularly
      international activities in educating BMHI specialists and the sharing of
      courseware. Method: An IMIA task force, nominated in 2006, worked on updating the
      recommendations' first version. These updates have been broadly discussed and
      refined by members of IMIA's National Member Societies, IMIA's Academic
      Institutional Members and by members of IMIA's Working Group on Health and
      Medical Informatics Education. Results and Conclusions: The IMIA recommendations
      center on educational needs for health care professionals to acquire knowledge
      and skills in information processing and information and communication
      technology. The educational needs are described as a three-dimensional framework.
      The dimensions are: 1) professionals in health care (e.g. physicians, nurses,
      BMHI professionals), 2) type of specialization in BMHI (IT users, BMHI
      specialists), and 3) stage of career progression (bachelor, master, doctorate).
      Learning outcomes are defined in terms of knowledge and practical skills for
      health care professionals in their role a) as IT user and b) as BMHI specialist.
      Recommendations are given for courses/course tracks in BMHI as part of
      educational programs in medicine, nursing, health care management, dentistry,
      pharmacy, public health, health record administration, and informatics/computer
      science as well as for dedicated programs in BMHI (with bachelor, master or
      doctor degree). To support education in BMHI, IMIA offers to award a certificate
      for high-quality BMHI education. It supports information exchange on programs and
      courses in BMHI through its Working Group on Health and Medical Informatics
      Education.

PMID- 20054504
TI  - Practical management measures for patients with recurrent herpes labialis.
AB  - Recurrent herpes labialis (RHL) is a common condition associated with the
      formation of vesicles around the mouth, often preceded by prodromal symptoms
      including tingling and burning. Treatment is targeted toward individual episodes,
      but in severe cases, suppressive therapy may be indicated. At present, no cure
      exists for this troublesome condition. The purpose of this article is to serve as
      a practical guide in the management of RHL by summarizing current treatments and
      discussing potential new therapies.

PMID- 20054505
TI  - Flares in childhood eczema.
AB  - Eczema is a major public health problem affecting children worldwide. Few studies
      have directly assessed triggers for disease flares. This paper presents evidence
      from a published systematic review and a prospective cohort study looking at
      flare factors in eczema. This systematic review suggested that foodstuffs in
      selected groups, dust exposure, unfamiliar pets, seasonal variation, stress, and
      irritants may be important in eczema flares. We performed a prospective cohort
      study that focused on environmental factors and identified associations between
      exposure to nylon clothing, dust, unfamiliar pets, sweating, shampoo, and eczema
      flares. Results from this study also demonstrated some new key findings. First,
      the effect of shampoo was found to increase in cold weather, and second,
      combinations of environmental factors were associated with disease exacerbation,
      supporting a multiple component disease model. This information is likely to be
      useful to families and may lead to the ability to reduce disease flares in the
      future.

PMID- 20054506
TI  - Tuberculosis - Risk of continued transmission in healthcare workers.
AB  - INTRODUCTION: Control of tuberculosis (TB) in healthcare workers requires an
      early recognition of contacts, the adoption of efficient protective measures and
      screening for cases of latent tuberculosis (TL) and recent TL. AIMS: Systematic
      screening for TB and TL in healthcare workers with contact with patients or other
      workers with TB and risk of contagion. MATERIAL AND METHODS: In a hospital with
      approximately 5400 workers 13 screenings were performed September 2007- December
      2008 due to risk of continued TB. These consisted of clinical observation,
      tuberculin skin test (PT), Quantiferon(R)-TB Gold (QTF) test if PT > or =10mm and
      <15 mm and chest X-ray. The diagnoses were performed according to the
      recommendations of the Portuguese Pulmonolgy Society (SPP). RESULTS: 792 workers
      (563 men; 229 women) were included in the 13 screenings. Of these, 75 presented
      symptoms and 31 had radiology abnormalities. PT was performed in 490 workers,
      with results <10 mm in 250, > or =10 and <15 mm in 175 (QTF positive in 36) and >
      or =15 mm in 65. Of the screened workers, 280 had a previous PT > or =15 mm, and
      therefore it was not repeated. 1 case of active TB was diagnosed in a worker, as
      well as 408 cases of TL (51.5%) and 42 cases of recent TL (5.3%). CONCLUSIONS: TB
      is considered an occupational disease in healthcare workers. The screening of
      contacts and TL cases is an important tool for an early diagnosis of active
      disease and for identifying the cases with higher risk of future disease.

PMID- 20054507
TI  - Quality of life in asthma patients.
AB  - In this paper we present a study whose main aim is the measurement of the Health
      Related Quality of Life (HRQoL) of patients with asthma and the presentation of a
      first draft of normative values as measured by the SF-6D for asthma patients. In
      addition, we investigate how far non-disease-specific HRQoL measures can
      distinguish groups in terms of sociodemographic characteristics. The Portuguese
      versions of the EQ-5D, SF-6D, AQLQ(S) and ACQ were administered using personal
      interviews to a representative sample of the Portuguese population with asthma.
      Most of the individuals did not report significant problems in the dimensions
      used, with the exception of the physical functioning, where individuals reported
      moderate limitations. The mean utility value was 0.86. Male gender, young,
      single, individuals with high educational attainment level, employed, individuals
      with high income and those residing in urban areas reported higher utility
      levels. As expected, those who were in a severe stadium of the disease reported
      lower mean utility levels than those who were in a less severe stadium of the
      disease. Normative values for the SF-6D were computed for patients with asthma by
      gender, age, marital status, educational attainment level, employment status,
      area of residence and average monthly net income. The preference-based measures
      used in this study distinguish patient groups with asthma in terms of socio-
      demographic groups. The normative values can be used in economic evaluation and
      clinical studies as they incorporate patients' preferences and translate the
      value attributed to patients' health state.

PMID- 20054508
TI  - Second hand smoke (SHS) exposure in children. An evaluation of a preventative
      measure.
AB  - AIMS: To evaluate the effectiveness of the preventative programme "Smoke-free
      Homes" undertaken in 4th year children and their parents or guardians, aiming to
      reduce children's exposure to second hand smoke (SHS) in the home. MATERIAL AND
      METHODS: This was a pre- and post-test pre-experimental study, in students from
      32 Braga district primary schools 2007/08. A self-administered and structured
      questionnaire was given out to 795 students in the classroom before and after the
      programme. In analysing data, we used the chi-squared test for the categorical
      variables. RESULTS: The rate of children exposed to regular or occasional SHS due
      to living with at least one smoker dropped from 42.2% to 32.6% (p=0.001). The
      percentage of students, children of smokers who stated that their father smoked
      regularly or occasionally at home, dropped from 68.0% pre-test to 51.6% posttest
      (p=0.000). No significant reduction was seen in mothers. CONCLUSION: Based on the
      data, we can conclude that the "Smoke-free Homes" programme was effective in
      preventing smoking in the home, and therefore reducing the rate of children
      exposed to SHS by about 10%. However, it appears that about a third of children
      are still exposed, which highlights the need for further measures in this area.
      Healthcare professionals, particularly those working in Paediatrics, should
      advise parents to quit smoking, especially in the home.

PMID- 20054509
TI  - Superior vena cava syndrome as tumour presentation.
AB  - Superior vena cava syndrome (SVCS) is characterised by gradual and insidious
      compression/obstruction of the superior vena cava (SVC). Upper chest and neck
      ingurgitation, plethoric face and oedema are the common symptoms/signs. It
      generally means the presence of neoplasm, namely lung cancer. AIM: Retrospective
      analysis of the patients admitted to S. Joao Hospital, Porto, Portugal, January
      1995-December 2006 with SVCS without previous diagnosis. Patients, tumour
      characteristics and prognostic factors were studied. MATERIAL AND METHODS: Data
      was collected by consulting the clinical files of 60 SVCS patients without
      previous diagnosis. Data was gathered on the patients' demographic
      characteristics (age, gender, smoking habits), performance status, histology,
      staging, treatment and overall survival. RESULTS: Lung cancer was observed in 87%
      of the patients. Small-cell lung cancer (SCLC) was the most frequent histological
      type; 41% of the patients. It is noticeable that 10% were diagnosed with non-
      Hodgkin's lymphoma. In terms of prognostic factors analysed, the absence of
      metastasis, the lymphoma's histological diagnosis, good performance status and
      non-smoker status were positively correlated with the survival rate. On the
      contrary SCLC was significantly correlated with a worse survival. CONCLUSIONS: In
      our analysis we concluded that SCLC, smokers and a poorer performance status as
      well as metastatic disease were unfavourable prognostic factors to SVCS as tumour
      presentation.

PMID- 20054510
TI  - CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer.
AB  - Lung cancer is considered an environment-related disease that develops as a
      consequence of exposure to mutagenic agents, namely those present in tobacco. The
      CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH)
      belonging to the cytochrome P450 system that plays a major role in the bio
      activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C
      transition) and m2 (A4889G transition), are associated with greater enzymatic
      activity and have been described as genetic susceptibility factors for lung
      cancer. The aim of this study was to verify if this association holds true in
      blood samples of 175 lung cancer patients and 217 non-cancer patients from
      Portugal's midlands region. The samples were studied by restriction fragment
      length polymorphism (RFLP) assay. The allelic frequencies of the mutant alleles
      were 0.12 for allele C and 1.14 for allele G in the control population. The
      results were not statistically different from those alleles in the patient
      population. There was also no statistically significant difference in genotype
      distribution in lung cancer patients and controls even when combining high risk
      genotypes. In our control sample, as in other populations of different ethnic
      origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude
      that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms
      are too rare to be of clinical relevance, and do not seem to be associated with
      susceptibility to lung cancer.

PMID- 20054511
TI  - Silicosis - brief review and experience of a pulmonology ward.
AB  - Silicosis is a diffuse interstitial fibronodular lung disease, caused by the
      inhalation of crystalline silica. We undertook a brief review of the topic,
      focusing on the most important aspects and performed a retrospective analysis of
      84 patients admitted to the Pulmonology Ward of the Coimbra University Hospital
      over a 10-year period whose main or secondary diagnosis was silicosis. We also
      present the most relevant clinical features and the conclusions drawn from this
      review. The authors assess patients' occupational history, changes in respiratory
      function study, the imaging findings and the associated complications.

PMID- 20054512
TI  - [Asthma treatment adherence].
AB  - Asthma is a very prevalent chronic disease in the general population,
      characterized by reversible obstruction of respiratory airways. Multiple studies
      demonstrate an improper control of the disease, and one of the main reasons for
      that is reduced adherence to treatment. Non -adherence can be classified as
      nonintentional or intentional, and the causes can be related to the motivations,
      beliefs and knowledge of the patient or due to the therapeutic regimen. The
      reasons for non -adherence are non -comprehension of the treatment goals; non 
      comprehension of disease severity; fears related to drugs; psychological
      conditions such as depression; complexity of treatment regimen; difficulties with
      administration route, mainly inhaler. After recognizing these issues as cause of
      non- -adherence, different approaches should be considered: set up a good
      physician -patient communication; promote asthma education; schedule regular
      appointments; simplify therapeutic regimen. It is important to promote adherence
      to achieve a good asthma control, and consequently a better quality of life and
      reduction of asthma associated costs.

PMID- 20054513
TI  - [Boundaries of the lung - Relationship to the gastrointestinal system].
AB  - The relation between the respiratory and gastrointestinal systems has been long
      recognized and depends on various anatomical, physiological and pathological
      mechanisms. The certain recognition of some interactions, such as the relation
      between asthma and gastroesophageal reflux, is more or less intuitive to the
      pulmonogist, whereas other areas of confluence are more easily missed, such as
      the relation between airway disorders and inflammatory bowel disease. The purpose
      of this article is to review the interaction between the lung and the
      gastrointestinal systems, as far as anatomy, physiology, pathology, clinical
      manifestations and therapeutical options go.

PMID- 20054514
TI  - [Bronchoscopic dilation techniques and topical application of mitomycin-C in the
      treatment of tracheal stenosis post intubation - two case reports].
AB  - Tracheal stenosis follows any injury to the airway mucosa, such as ischaemic,
      traumatic and other injuries. The treatment of tracheal stenosis remains a
      challenging problem despite all the advances in endoscopic and surgical
      techniques. Scar formation and reestenosis are the main causes of treatment
      failure. The authors present two cases of successful treatment of a tracheal
      stenosis after tracheal injury from prolonged oro -tracheal intubation /
      tracheostomy following dilatation with rigid broncoscope and laser therapy,
      associated with topical application of mitomycin C as an adjuvant treatment.

PMID- 20054515
TI  - [Bullous emphysema associated with drug abuse].
AB  - Bullous emphysema is characterized by permanent enlargement of airspaces distal
      to the terminal bronchiole accompanied by destruction of alveolar walls. Several
      aetiologies have been described, namely deficiency of alpha1 -antitrypsin and the
      consumption of tobacco. With the exception of the deficiency of alpha1 
      antitrypsin, some cases of bullous emphysema in the young adult continue without
      known aetiology. Some cases of bullous emphysema have been described, emphasising
      the relationship between the disease and drug consumption. The association
      possibly creates the conditions for the development of large lung bullae, with
      particular exuberance for the superior lobes. The authors describe two clinical
      cases of young patients, with history of consumption of smoked substance abuse
      and bullous emphysema.

PMID- 20054516
TI  - [Spontaneous multiloculated pneumomediastinum in a newborn: case report].
AB  - Spontaneous pneumomediastinum in a term baby without assisted ventilation or
      known underlying pulmonary disease is uncommon. The authors present a case report
      of a term baby delivered by caesarean that developed mild respiratory distress
      after birth. The pulmonary X -ray on day 2 showed an abnormal gas lucency
      adjacent to the left cardiac border elevating thymic border indicative of
      pneumomediastinum. Our case demonstrates two unique features of neonatal
      pneumomediastinum - the presence of multiple internal septae and its tendency to
      loculate locally. The authors present this case for its rarity and the specific
      imagiological aspects.

PMID- 20054517
TI  - [Musculoskeletal tuberculosis - a clinical case report].
AB  - Tuberculosis of the chest wall constitutes 1% to 5% of all cases of
      musculoskeletal TB. Abscesses of the chest wall are rare tuberculous locations.
      Because of the resurgence of the tuberculosis associated to AIDS, that diagnosis
      must be considered more frequently. The authors present a case of osseous
      tuberculosis with an abscess rib in a patient with HIV. The combination of
      indolent onset of symptoms and compatible radiographic findings, strongly
      suggests the diagnosis. However, the confirmation with positive culture or
      histopathologic are essential for definitive diagnosis.

PMID- 20054518
TI  - [Thymic carcinoid - case report].
AB  - Primary neuroendocrine tumours (carcinoid tumours) account for about 4% of
      anterior mediastinal tumours concerning thymus localization. They appear to have
      a male predilection (3:1 ratio) and occur mostly between 40 and 60 years of age.
      Classified primarily as thymomas, they have been considered a different group of
      thymic neoplasia since 1972. They can be biologically active, mostly associated
      with MEN -1 (19 -25% of patients and more aggressive in these cases). As a
      locally invasive disease, with recurrence and metastasis in a high percentage of
      cases, it correlates with a poor prognosis. Staging is the most important
      determinant of survival. Encapsulated tumours diagnosed in early stages have an
      excellent prognosis, while locally invasive tumours in more advanced stages have
      a relatively poor prognosis as happens with thymomas. Complete surgical removal
      is the critical factor for long -term survival rates and the basis for treatment
      of all thymic tumours, independent of histologic type. As an important cause of
      death, especially in carcinoid tumours associated with MEN -1 and Cushing's
      syndrome, some authors advocate the need for profilactic thymectomy in these
      patients.

PMID- 20054519
TI  - [Lymphangioleiomyomatosis - report of three cases].
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease of unknown aetiology.
      It is characterized by proliferation of abnormal smooth -muscle cells throughout
      the peribronchial, perivascular and perilymphatic regions of the lung. LAM may
      occur sporadically, in association with tuberous sclerosis complex (TSC) or
      inheritable multiorgan hamartomatosis. In either situation, LAM occurs almost
      exclusively in women of reproductive age, and approximately one third of the
      patients with TSC have LAM2. The authors review the cases of three female
      patients diagnosed with LAM based on clinical and radiological findings. A brief
      review of the disease is then presented.

PMID- 20054520
TI  - High-glucose and advanced glycosylation end products increased podocyte
      permeability via PI3-K/Akt signaling.
AB  - Regardless of the underlying disease, the proteinuric condition demonstrates
      ultrastructural changes in podocytes with retraction and effacement of the highly
      specialized interdigitating foot processes. To investigate how high-glucose (HG)
      and advanced glycosylation end products (AGE) induce podocyte phenotypical
      changes, including quantitative and distributional changes of zonula occludens
      (ZO)-1 protein and search for the signaling mechanisms, we cultured rat
      glomerular epithelial cells (GEpC) and mouse podocytes under: (1) normal glucose
      (5 mM, control); (2) HG (30 mM); (3) AGE-added; or (4) HG plus AGE-added
      conditions. HG plus AGE increased the permeability of monolayered GEpCs and
      induced ultrastructural separation between confluent GEpCs. ZO-1 moved to inner
      actin filament complexes in both AGE- and/or HG by confocal imaging. HG plus AGE
      added condition also decreased ZO-1 protein amount and mRNA expression compared
      to normal glucose or osmotic control conditions. We could also confirm the
      induction of RAGE (receptor for AGE) and PI3-K/Akt signaling pathway by AGE and
      HG. In addition, LY294002, a PI3-K inhibitor, could prevent the quantitative and
      distributional changes of ZO-1 and RAGE and the increased permeability induced by
      HG and AGE. These findings suggest that diabetic conditions induce the podocyte
      ZO-1 changes via RAGE and PI3-K/Akt signaling, leading to increased permeability.

PMID- 20054521
TI  - Genetic diversity trends in twentieth century crop cultivars: a meta analysis.
AB  - In recent years, an increasing number of papers has been published on the genetic
      diversity trends in crop cultivars released in the last century using a variety
      of molecular techniques. No clear general trends in diversity have emerged from
      these studies. Meta analytical techniques, using a study weight adapted for use
      with diversity indices, were applied to analyze these studies. In the meta
      analysis, 44 published papers were used, addressing diversity trends in released
      crop varieties in the twentieth century for eight different field crops, wheat
      being the most represented. The meta analysis demonstrated that overall in the
      long run no substantial reduction in the regional diversity of crop varieties
      released by plant breeders has taken place. A significant reduction of 6% in
      diversity in the 1960s as compared with the diversity in the 1950s was observed.
      Indications are that after the 1960s and 1970s breeders have been able to again
      increase the diversity in released varieties. Thus, a gradual narrowing of the
      genetic base of the varieties released by breeders could not be observed.
      Separate analyses for wheat and the group of other field crops and separate
      analyses on the basis of regions all showed similar trends in diversity.

PMID- 20054522
TI  - Long-term lifestyle intervention lowers the incidence  of stroke in Japanese
      patients with type 2 diabetes:  a nationwide multicentre randomised controlled 
      trial (the Japan Diabetes Complications Study).
AB  - AIMS/HYPOTHESIS: The aim of the study was to clarify whether a therapeutic
      intervention focused on lifestyle modification affected the incidence of vascular
      complications in patients with established diabetes. METHODS: A total of 2,033
      eligible Japanese men and women aged 40-70 years with type 2 diabetes from 59
      institutes were randomised to a conventional treatment group (CON), which
      continued to receive the usual care, and a lifestyle intervention group (INT),
      which received education on lifestyle modification regarding dietary habits,
      physical activities and adherence to treatment by telephone counselling and at
      each outpatient clinic visit, in addition to the usual care. Randomisation and
      open-label allocation were done by a central computer system. Primary analysis
      regarding measurements of control status and occurrence of macro- and
      microvascular complications was based on 1,304 participants followed for an 8
      year period. RESULTS: Although status of control of most classic cardiovascular
      risk factors, including body weight, glycaemia, serum lipids and BP, did not
      differ between groups during the study period, the incidence of stroke in the INT
      group (5.48/1,000 patient-years) was significantly lower than in the CON group
      (9.52/1,000 patient-years) by Kaplan- Meier analysis (p=0.02 by logrank test) and
      by multivariate Cox analysis (HR 0.62, 95% CI 0.39-0.98, p=0.04). The incidence
      of CHD, retinopathy and nephropathy did not differ significantly between groups.
      Lipoprotein(a) was another significant independent risk factor for stroke.
      CONCLUSIONS/INTERPRETATION: These findings suggest that lifestyle modification
      had limited effects on most typical control variables, but did have a significant
      effect on stroke incidence in patients with established type 2 diabetes. CLINICAL
      TRIAL REGISTRATION: UMIN-CTR C000000222 FUNDING: The Ministry of Health, Labour
      and Welfare, Japan

PMID- 20054523
TI  - Features of distinct contractions induced with a high  and a low concentration of
      KCl, noradrenaline,  and histamine in swine lingual artery.
AB  - We investigated the features of swine lingual artery contraction induced with
      different strengths of stimulation. Endothelium-denuded artery rings were
      contracted with two concentrations of KCl, noradrenaline, and histamine with or
      without Y-27632, sodium nitroprusside (SNP), 2,2-diphenyl-1,3,2-oxaza-borolidine
      internal salt (2- APB), and extracellular Ca2+. While stored at 5 degrees C up to
      3 days, artery rings remained active to strong stimulation but became inactive to
      weak stimulation if prior warming was lacking. Artery rings contracted slowly and
      progressively to weak stimulation but rapidly to strong stimulation and then kept
      a plateau or slightly relaxed. Y-27632, SNP, and 2-APB, irrespective of
      extracellular Ca2+, attenuated weak-stimulation-induced contractions to much
      greater extents except that 2-APB similarly diminished contractions to both
      noradrenaline concentrations. Without extracellular Ca2+, transitory contractions
      occurred with one peak to strong stimulation and two small peaks to weak
      stimulation, though one full peak to both noradrenaline concentrations. Artery
      rings lost stimulant responsiveness when extracellular Ca2+ was absent, but
      subsequent Ca2+ reintroduction without coexisting stimulant triggered transient
      contractions, which were as large as contractions to weak stimulation with
      extracellular Ca2+ and ceased with Y-27632, SNP, and 2-APB. These results
      collectively suggest that, in the lingual artery, its contraction properties
      shift coupling with strengths of both receptor- and voltage-mediated stimulation,
      with the tonic-like component being dominant in weak-stimulation-induced
      contraction.

PMID- 20054524
TI  - Antiulcerogenic activity of extract, fractions,  and some compounds obtained from
      Polygala cyparissias  St. Hillaire & Moquin (Polygalaceae).
AB  - The present study evaluates the gastroprotective properties of acetone extract,
      chloroform, and methanol fractions, alpha-spinasterol (1); 1,3-dihydroxy-7
      methoxyxanthone (2); and 1,7-dihydroxy-2,3-methylenedioxyxanthone (3) obtained
      from Polygala cyparissias (Polygalaceae). Gastroprotective assays were performed
      in mice using ethanol/HCl and nonsteroidal anti-inflammatory drug
      (NSAID)/bethanechol-induced ulcer models. Chloroformic fraction showed no
      interesting results. On the other hand, in the ethanol/HCl-induced ulcer model,
      the treatment using doses of 50, 125, and 250 mg/kg promoted ulcer inhibition of
      45.19+/-12.93%, 62.99+/-3.49%, and 67.40+/-4.75% for acetone extract and 43.70+/
      5.12%, 64.56+/-5.64%, and 74.49+/-6.13% for methanol fraction. In the model of
      NSAID/bethanechol-induced ulcer, the ulcer inhibitions in the same doses were
      28.12+/-12.45%, 60.16+/-6.58%, and 77.86+/-7.18% for the acetone extract and
      46.09+/-6.92%, 67.45+/-4.36%, and 75.00+/-2.92% for the methanol fraction. In
      view of the antiulcer potential of the acetone extract and its high yield and
      xanthone content, it was submitted to chromatographic procedures, giving
      compounds 1-3, which were also evaluated in the ethanol-induced ulcer model. The
      results showed that at a dose of 50 mg/kg, these compounds reduced the percentage
      of ulcer by around 71.26+/-9.40%, 81.10+/-5.75%, and 86.22+/-3.42%, for compounds
      1, 2, and 3, respectively. The antiulcerogenic activity of P. cyparissias may be
      attributed, at least in part, to these compounds.

PMID- 20054525
TI  - The GABAB receptor agonist baclofen administered into the median and dorsal raphe
      nuclei is rewarding as shown by intracranial self-administration and conditioned
      place preference in rats.
AB  - RATIONALE: The midbrain raphe regions have long been implicated in affective
      processes and disorders. There is increasing evidence to suggest that the median
      (MR) and dorsal raphe nuclei (DR) tonically inhibit reward-related processes.
      OBJECTIVES: Stimulation of GABAB receptors in the midbrain raphe nuclei is known
      to inhibit local neurons, especially serotonergic neurons. We sought to determine
      if injections of the GABAB receptor agonist baclofen into the MR or DR are
      rewarding, using intracranial self-administration and conditioned place
      preference. RESULTS: Rats quickly learned to lever press for infusions of
      baclofen (0.1-2.5 mM) into the MR, but not the ventral tegmental area or central
      linear nucleus. Rats increased lever pressing associated with intra-DR baclofen
      infusions, but not readily. Baclofen self-administration into the MR or DR was
      attenuated by coadministration of the GABAB receptor antagonist SCH 50911 (1 mM)
      or systemic pretreatment with the dopamine receptor antagonist SCH 23390 (0.025
      mg/kg, i.p.). In addition, intra-DR and intra-MR injections of baclofen induced
      conditioned place preference; injection into DR was more effective. CONCLUSIONS:
      Baclofen injections into the midbrain raphe nuclei are rewarding. Baclofen was
      more readily self-administered into the MR than into the DR, while baclofen
      injections into the DR more readily induced conditioned place preference than
      those into the MR. These sites may be differentially involved in aspects of
      reward. These findings suggest that MR or DR neurons containing GABAB receptors
      are involved in tonic inhibitory control over reward processes.

PMID- 20054526
TI  - CYP3A activity influences imatinib response in patients with chronic myeloid
      leukemia: a pilot study on in vivo CYP3A activity.
AB  - PURPOSE: Imatinib is currently used for the treatment of chronic myeloid leukemia
      (CML). The main metabolite CGP74588 has similar potency to that of imatinib and
      is a product of CYP3A4 and CYP3A5 metabolism. However, the clinical significance
      of the metabolism on therapeutic response and pharmacokinetics is still unclear.
      We designed this study to investigate the role of the CYP3A activity in the
      response to imatinib therapy. METHODS: Fourteen CML patients were phenotyped for
      in vivo CYP3A activity using quinine as a probe drug. The plasma concentration
      ratio of quinine and its CYP3A metabolite was used for assessing CYP3A activity.
      The patients were divided into complete molecular responders with undetectable
      levels of BCR-ABL transcripts after 12 months of therapy and into partial
      molecular responders who had failed to achieve a complete molecular response.
      RESULTS: Patients that achieved complete molecular response showed significantly
      (Mann-Whitney U-test, p=0.013) higher in vivo CYP3A activity (median quinine
      metabolic ratio = 10.1) than patients achieving partial molecular response
      (median = 15.9). CONCLUSIONS: These results indicate a clinical significance of
      the CYP3A activity and its metabolic products in CML patients treated with
      imatinib.

PMID- 20054527
TI  - Degradation studies of new substitutes for perfluorinated surfactants.
AB  - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are manmade,
      stable perfluorosurfactants. The properties of perfluoroalkylated compounds that
      cause them to persist in the environment are also the properties that made them
      attractive compounds for industrial usage for over 50 years. Due to the unique
      properties of the carbon-fluorine bond and the polarity of perfluoroalkyl groups,
      potential substitutes to replace perfluorinated surfactants in most cases
      continue to be perfluoroalkyl based. Thus, issues of persistence in the
      environment remain. There is a need to test emerging new substitute surfactants
      for biodegradability. This study involved degradability measurements of emerging
      perfluorinated surfactant substitutes. The stability of the substitutes of
      perfluorinated surfactants was tested by employing advanced oxidation processes,
      which were based on degradation by ultraviolet lamp, hydrogen peroxide, or both,
      followed by conventional tests, among them an automated method based on the
      manometric respirometry test (OECD 301 F; OxiTop), closed-bottle test (OECD 301
      D), and standardized fixed-bed bioreactor on perfluorobutane sulfonate,
      fluorosurfactant Zonyl, two fluoraliphatic esters (NOVEC FC-4430 and NOVEC FC
      4432), and 10-(trifluoromethoxy) decane 1 sulfonate. Most of these new
      surfactants are well established in the marketplace and have been used in several
      applications as alternatives to PFOS- and PFOA-based surfactants. Ready
      biodegradation tests for fluoroaliphatic esters, the fluorosurfactant Zonyl,
      perfluorobutane sulfonate, and 10-(trifluoromethoxy) decane-1-sulfonate using the
      manometric respirometry test (OxiTop) did not meet the ready biodegradability
      test criteria. However, 10-(trifluoromethoxy) decane-1-sulfonate was observed to
      be degradable when a standardized fixed-bed bioreactor test was applied.

PMID- 20054529
TI  - Infantile form of scimitar syndrome with contralateral pulmonary vein stenosis.
AB  - Infantile scimitar syndrome (SS) carries significant mortality. Consistent
      management guidelines have not been well established, and outcomes continue to be
      disappointing. We present our experience managing an SS patient with complex
      anatomy who developed stenosis of the pulmonary veins contralateral to the
      hypoplastic lung.

PMID- 20054528
TI  - Postoperative use of oral sildenafil in pediatric patients with congenital heart
      disease.
AB  - We sought to determine the efficacy of postoperative oral sildenafil therapy
      (OST) in pediatric patients with congenital heart disease (CHD). A retrospective
      review of 45 postoperative patients with CHD who received OST was performed.
      Patients were categorized into three groups according to clinical indications:
      (1) to stabilize pulmonary vascular reactivity after biventricular repair (group
      1 [n = 15]), (2) to lower pulmonary vascular resistance after bidirectional
      cavopulmonary shunt (group 2 [n = 12]), and (3) to improve post-Fontan
      hemodynamics (group 3 [n = 18]). Thirty-four patients (34 of 45 [75.6%]) had
      received inhaled nitric oxide (iNO) while on OST. Mean pulmonary arterial
      pressure (mPAP), mean systemic blood pressure (mSBP), and peripheral oxygen
      saturation (SpO(2)) were recorded during the first 24 hours after the initiation
      of OST. In group 1, the baseline mPAP/mSBP ratio (0.60 +/- 0.17) decreased
      significantly after the second (0.46 +/- 0.14, p = 0.004) and fourth (0.50 +/-
      0.18, p = 0.025) doses of OST. In group 2, baseline SpO(2) (71.0 +/- 12.3%)
      increased after the fourth dose (75.1 +/- 12.3%, p = 0.04) of OST, without
      significant changes in mPAP. In group 3, baseline mPAP (14.8 +/- 3.3 mmHg)
      decreased significantly after the first (13.9 +/- 2.8 mmHg, p = 0.025) and second
      (13.3 +/- 1.9 mmHg, p = 0.016) doses of OST, without changes in SpO(2). In thirty
      one (31 of 34 [92%]) subjects, iNO was discontinued within a median of 2 days
      after the initiation of OST, without rebound phenomena. There were no OST-related
      complications. Sildenafil citrate can be used safely in postoperative pediatric
      patients with CHD. Benefits from OST may be manifested differently in various
      clinical settings.

PMID- 20054530
TI  - An old autopsy report sheds light on a "new" disease: infantile polyarteritis
      nodosa and kawasaki disease.
AB  - Although Kawasaki disease (KD) was first discovered and identified in Japan by
      Kawasaki in the 1960s, fatal KD cases resulting from coronary artery aneurysms
      had been identified retrospectively in the West as early as 1871. Kawasaki
      initially postulated that this disease was a new, as yet unidentified, self
      limiting illness with no fatal coronary sequelae. The connection between fatal
      cases, then diagnosed as infantile polyarteritis nodosa, was not made until the
      late 1970s. Kawasaki's thoughts were reinforced by an apparent absence of
      nonfatal cases in the West before 1967. Close examination of a 1948 autopsy
      report suggests that nonfatal cases of KD did indeed exist, at least in the
      United States, before its emergence in Japan in the early 1950s. These nonfatal
      cases of KD were misdiagnosed as Stevens-Johnson syndrome. The autopsy report
      reviewed in this article reinforces the likelihood that KD did occur in the
      United States before it was identified as Kawasaki disease in Japan.

PMID- 20054531
TI  - 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular
      development.
AB  - Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1
      maps within the region of 22q11 deleted in humans with DiGeorge or
      velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that
      recapitulate major features of the syndrome, notably abnormal growth and
      remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency
      phenotype is modified by genetic background and by mutations in putative
      downstream targets. Homozygous null mutations of Tbx1 have more severe defects
      including failure of outflow tract septation, and absence of the caudal
      pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity
      has been linked to alterations in the expression of various genes involved in
      cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are
      dysregulated in Tbx1 mutants. This article summarises the tissue specific and
      temporal requirements for Tbx1, and attempts to synthesis what is know about the
      developmental pathways under its control.

PMID- 20054532
TI  - Transcriptional control of left-right patterning in cardiac development.
AB  - The heart develops from a simple left-right (L-R) symmetrical tube. Through a
      complex process of looping and remodelling, it becomes a highly L-R asymmetrical
      organ with distinct asymmetries in both morphology and function. Abnormal cardiac
      L-R patterning can result in a spectrum of defects that include, dextrocardia (a
      malposition of the heart to the right), isomerism of the atria (both atria being
      morphologically right-sided or left-sided), abnormal ventricular topology (e.g.
      the morphological left ventricle being dextral to the morphological right
      ventricle) or mirror-image topology (associated with situs inversus).
      Intermediate forms include abnormalities such as situs ambiguus and heterotaxia.
      L-R patterning abnormalities are typically associated with cardiac malformations,
      and it has become clear that an isolated septal, outflow tract and aortic arch
      malformation may be the only presenting manifestation of an L-R patterning
      defect. In the last two decades, there have been seminal advances in our
      understanding of the mechanisms controlling L-R patterning, and how mutations in
      L-R patterning genes result in human cardiac malformation. In this review, we
      provide an overview of the transcriptional mechanisms that result in asymmetric
      gene activation in mammals, how they receive information from signalling
      pathways, and how this translates to abnormal cardiac development.

PMID- 20054533
TI  - Characterization of the zebrafish T cell receptor beta locus.
AB  - Zebrafish (Danio rerio) has become an increasingly important model for
      immunological study. Its immune system is remarkably similar to that of mammals
      and includes both the adaptive and innate branches. Zebrafish T cells express
      functional T cell receptors (TCR), and all four TCR loci are present within the
      genome. Using 5'-rapid amplification of cDNA ends, we cloned and sequenced
      zebrafish TCRbeta transcripts. TCRbeta VDJ coding joints demonstrate conservation
      of mechanisms used by other vertebrate species to increase junctional diversity.
      Using the sequences obtained, along with previously published data, we
      comprehensively annotated the zebrafish TCRbeta locus. Overall, organization of
      the locus resembles that seen in mammals. There are 51 V segments, a single D
      segment, 27 Jbeta1 segments, a single Jbeta2 segment, and two constant regions.
      This description of the zebrafish TCRbeta locus has the potential to enhance
      immunological research in zebrafish and further our understanding of mammalian
      TCR repertoire generation.

PMID- 20054534
TI  - Purification, cloning, and overexpression of an alcohol dehydrogenase from
      Nocardia globerula reducing aliphatic ketones and bulky ketoesters.
AB  - For the huge amount of chiral chemicals and precursors that can potentially be
      produced by biocatalysis, there is a tremendous need of enzymes with new
      substrate spectra, higher enantioselectivity, and increased activity. In this
      paper, a highly active alcohol dehydrogenase is presented isolated from Nocardia
      globerula that shows a unique substrate spectrum toward different prochiral
      aliphatic ketones and bulky ketoesters as well as thioesters. For example, the
      enzyme reduced ethyl 4-chloro-3-oxo butanoate with an ee >99% to (S)-4-chloro-3
      hydroxy butanoate. Very interesting is also the fact that 3-oxobutanoic acid tert
      butylthioester is reduced with 49.4% of the maximal activity while the
      corresponding tert-butyloxyester is not reduced at all. Furthermore, it has to be
      mentioned that acetophenone, a standard substrate for many known alcohol
      dehydrogenases, is not reduced by this enzyme. The enzyme was purified from wild
      type N. globerula cells, and the corresponding 915-bp-long gene was determined,
      cloned, expressed in Escherichia coli, and applied in biotransformations. The N.
      globerula alcohol dehydrogenase is a tetramer of about 135 kDa in size as
      determined from gel filtration. Its sequence is related to several hypothetical 3
      hydroxyacyl-CoA dehydrogenases whose sequences were derived by whole-genome
      sequencing from bacterial sources as well as known mammalian 3-hydroxyacyl-CoA
      dehydrogenases and ss-hydroxyacyl-CoA dehydrogenases from different clostridiae.

PMID- 20054535
TI  - Molecular cloning and characterization of amylase from soil metagenomic library
      derived from Northwestern Himalayas.
AB  - The increasing demand for novel biocatalysts stimulates exploration of resources
      from soil. Metagenomics, a culture independent approach, represent a sheer
      unlimited resource for discovery of novel biocatalysts from uncultured
      microorganisms. In this study, a soil-derived metagenomic library containing
      90,700 recombinants was constructed and screened for lipase, cellulase, protease
      and amylase activity. A gene (pAMY) of 909 bp encoding for amylase was found
      after the screening of 35,000 Escherichia coli clones. Amino acid sequence
      comparison and phylogenetic analysis indicated that pAMY was closely related to
      uncultured bacteria. The molecular mass of pAMY was estimated about 38 kDa by
      sodium dodecyl sulphate polyacrylamide gel electrophoresis. Amylase activity was
      determined using soluble starch, amylose, glycogen and maltose as substrates. The
      maximal activity (2.46 U/mg) was observed at 40 degrees C under nearly neutral pH
      conditions with amylose; whereas it retains 90% of its activity at low
      temperature with all the substrates used in this study. The ability of pAMY to
      work at low temperature is unique for amylases reported so far from microbes of
      cultured and uncultured division.

PMID- 20054536
TI  - Correlation of the cross-over ratio of the cross-over sign on conventional pelvic
      radiographs with computed tomography retroversion measurements.
AB  - OBJECTIVE: To find a correlation between the cross-over ratio of the cross-over
      sign on conventional anteroposterior (AP) pelvic radiographs and retroversion
      measurements ('roof-edge angle' and 'equatorial-edge angle) on computed
      tomography (CT) scans. This would facilitate the interpretation of the cross-over
      sign regarding the amount of acetabular retroversion. MATERIALS AND METHODS:
      Correctly projected AP pelvic radiographs (2,925 hips) were examined for the
      presence of the cross-over sign (COS), and the overlap ratio of the COS was
      measured. On CT scans of the same patients the 'roof-edge angle' (RE angle) and
      the 'equatorial-edge angle' (EE angle) were also calculated. RESULTS: A
      statistically significant but only weak relationship could be found between the
      overlap ratio of the COS and the 'roof-edge angle' (P < 0.0001; correlation
      coefficient -0.486) and between this ratio and the 'equatorial-edge angle' (P <
      0.0001; correlation coefficient -0.395). CONCLUSION: A relationship between the
      overlap ratio and orientation measurements on CT scans could be found, but it was
      less strong than expected.

PMID- 20054537
TI  - MRI findings of an inflammatory variant of well-differentiated liposarcoma.
AB  - The inflammatory variant of well-differentiated liposarcoma (WDLPS) is a rare
      subtype. We present a 75-year-old woman who had a tumor that was difficult to
      diagnose preoperatively. Magnetic resonance imaging of the tumor revealed a
      large, lobulated heterogeneous soft tissue mass with a distinctive pattern of
      intermingled well-differentiated fatty elements and nodular areas of high T2
      intensity tissue.

PMID- 20054538
TI  - Impact of the standardized medial-to-lateral approach on outcome of laparoscopic
      colorectal resection. is it a fair comparison?

PMID- 20054539
TI  - CT scan for suspected acute abdominal process: impact of combinations of IV,
      oral, and rectal contrast.
AB  - BACKGROUND There are limited data available on the ability of computed tomography
      (CT) to accurately diagnose abdominopelvic pathology in acutely ill inpatients
      suspected of having an acute abdominal process. The purpose of this study was to
      evaluate the diagnostic accuracy of abdominal/pelvic CT with varying use of
      contrast agents in hospitalized patients. METHODS A retrospective review of all
      hospital inpatients (3/1/07-5/31/07) who underwent urgent or emergent
      abdominal/pelvic CT with any combination of contrast, intravenous (IV), oral,
      rectal, or unenhanced for a suspected acute abdominal process was performed. Data
      collected included demographics, combination of contrast used, CT diagnosis, time
      from CT scan to subsequent intervention, intervention type, and actual diagnosis
      of the acute abdominal process. Accuracy of CT was compared between enhanced and
      unenhanced imaging using Fisher's exact test. RESULTS A total of 661 patients
      were identified. Use of IV contrast alone was found in 54.2% of CT scans and was
      correct in 92.5% of cases. IV and oral contrast was used in 22.2% of CT scans and
      was 94.6% correct. Unenhanced imaging was performed in 16.2% and was correct in
      92.5%. Oral contrast alone was used in 7.0% and was 93.5% correct. There was no
      significant difference in the ability to correctly diagnose a suspected acute
      abdominal process when enhanced CT imaging was compared to unenhanced (p > 0.05).
      CONCLUSIONS CT contrast administration in critically ill hospitalized patients is
      not necessary to accurately diagnose an acute abdominal process. Eliminating the
      use of contrast may improve patient comfort, decrease patient risk, and minimize
      financial cost.

PMID- 20054540
TI  - Vitamin D3 deficiency is associated with late-onset hypocalcemia after minimally
      invasive parathyroidectomy in a vitamin D borderline area.
AB  - BACKGROUND: Concurrent vitamin D(3) deficiency is common in primary
      hyperparathyroidism (pHPT). We aimed to examine the clinicopathologic features
      and short-term outcomes of vitamin D(3)-deficient patients after minimally
      invasive parathyroidectomy (MIP). METHODS: Over 2-year period, 80 consecutive MIP
      patients had preoperative-fasting 25-hydroxyvitamin D(3) (25OHD(3)) checked.
      Forty-five patients had a 25OHD(3) level <20 ng/ml and were defined as deficient.
      Intraoperative parathyroid hormone (IOPTH) assay was used for all MIP.
      Postoperative adjusted calcium (Ca) was checked at 6, 16 (with intact PTH), and
      24 h. Oral calcium and vitamin D supplements were given if hypocalcemic symptoms
      developed or Ca < 2.00 mmol/l. Late-onset hypocalcemia (LOH) was defined as
      symptoms developed after 24 h. RESULTS: Both deficient and nondeficient groups
      had similar demographic data and bone density scores. The deficient group had
      significantly higher PTH (190 vs. 121 pg/ml, p = 0.015). Although IOPTH in the
      deficient group were higher at induction and 0 min after excision, the percentage
      drop from induction to 10 min after excision was similar. Ca was similar at 6 and
      16 h in the two groups but was significantly lower in the deficient group at 24 h
      (2.10 vs. 2.45 mmol/l, p = 0.033). At 1 week, the proportion of LOH was
      significantly higher in the deficient group (12/42 vs. 3/34, p = 0.043) and in
      those with preoperative PTH > 100 pg/ml (15/57 vs. 0/19, p = 0.013). CONCLUSIONS:
      Vitamin D(3) deficiency was associated with a higher preoperative PTH level and a
      greater risk of LOH after MIP. However, the likely cause of LOH remains unclear
      as both low preoperative vitamin D(3) and high PTH levels could be responsible.

PMID- 20054541
TI  - Meta-analysis of survival of patients with stage IV colorectal cancer managed
      with surgical resection versus chemotherapy alone.
AB  - BACKGROUND There is no consensus regarding the appropriate management of
      asymptomatic and minimally symptomatic patients with stage IV colorectal cancer
      and irresectable metastases. METHODS A literature search was conducted on Medline
      and Embase. Outcome measures included: survival; postoperative morbidity and
      mortality; complications from the primary tumor and the need for surgery to
      manage complications; the likelihood of curative surgery after initial response
      to primary therapy; and length of hospital stay. Quantitative meta-analysis was
      performed where appropriate. RESULTS Eight retrospective studies, including 1,062
      patients, met the criteria for inclusion in this study. Meta-analysis has shown
      an improvement in the survival of patients managed with palliative resection of
      their primary tumor, with an estimated standardized median difference of 6.0
      months (standardized difference, 0.55; 95% confidence interval (CI), 0.29, 0.82;
      p < 0.001). Patients managed with chemotherapy alone were 7.3 times more likely
      to have a complication from the primary tumor (95% CI, 1.7, 34.4; p = 0.008).
      There was no difference in the response rates to chemotherapy, making metastatic
      disease amendable to curative resection (0.85; 95% CI 0.40, 1.8; p = 0.662).
      CONCLUSIONS To date, only retrospective data are available, showing that
      palliative resection of the primary tumor in asymptomatic or minimally
      symptomatic patients with stage IV colorectal cancer is associated with longer
      survival. Resection of the primary tumor reduces the likelihood of complications
      from the primary tumor and avoids the need for emergency procedures.

PMID- 20054542
TI  - Correlation between preoperative endoscopic and intraoperative findings in
      localizing colorectal lesions.
AB  - BACKGROUND: Colonoscopy findings compared with findings at time of surgery have a
      discrepancy rate of 3-21%. The objective of our study was to investigate this
      discrepancy and provide potential resolutions. METHODS: In this retrospective
      study, we identified 400 patients who underwent colonoscopy followed by colon
      resection at our community hospitals in 1999-2006. Discrepancies between
      colonoscopy and intraoperative findings were noted. Each discrepancy was
      classified as major if the surgical procedure had to be altered, the lesion was
      missed, an unnecessary segment was removed, or the incision was extended. A
      discrepancy was classified as minor if there was no alteration in planned
      surgery. RESULTS: Of the 400 cases, 160 (40%) were located in the right colon, 13
      (3%) were in the transverse colon, 185 (46%) were in the left colon, and 42 (11%)
      were in the rectum. A total of 48 (12%) discrepancies between colonoscopy and
      intraoperative findings were identified: 26 (54%) were major and 22 (46%) were
      minor. Thirteen (27%) were in the proximal colon (3 major and 10 minor
      discrepancies), 3 (6.3%) were in the transverse colon (all major), 22 (46%) were
      in the distal colon (17 major and 5 minor), and 10 (21%) were in the rectum (3
      major, 7 minor). Major discrepancies were significantly higher in the left colon
      (17 of the 185 left-sided lesions; 9.1%) than in the right colon (3/160; 1.9%; P
      = 0.045). CONCLUSIONS: In our study, colonoscopy has an error rate of 12% when
      used to localize tumors; more than half of these patients require significant
      unanticipated changes in their surgery. The discrepancies are significantly
      higher in left side of colon.

PMID- 20054543
TI  - Significance of lavage cytology in advanced gastric cancer patients.
AB  - BACKGROUND: Lavage cytology positive (Cy1) is well known as a poor prognostic
      factor in advanced gastric cancer patients. However, the optimal therapeutic
      strategy for patients with Cy1 has not yet been established. The aim of this
      study was to evaluate the clinical significance of Cy1 for the purpose of
      establishing a suitable therapeutic strategy. METHODS: The data of 996
      consecutive advanced gastric cancer patients who underwent gastrectomy between
      1992 and 1998 at the National Cancer Center Hospital were retrospectively
      studied. RESULTS: The 2- and 5-year survival rates of the patients who underwent
      gastrectomy without any other noncurative factors besides Cy1 were 25.3 and 7.8%,
      respectively. When the analysis was limited to type 4 advanced gastric cancer
      patients, none of the patients with Cy1 survived for more than 40 months.
      CONCLUSIONS: The prognosis of gastric cancer patients with Cy1 is very poor. Some
      patients show long survival after standard gastrectomy with D2 lymph node
      dissection; however, the prognosis of type 4 gastric cancer patients with Cy1 is
      so poor that multimodality therapy, including perioperative chemotherapy, is
      essential.

PMID- 20054544
TI  - Paracetamol reduces postoperative pain and rescue analgesic demand after robot
      assisted endoscopic thyroidectomy by the transaxillary approach.
AB  - BACKGROUND: Postoperative pain following endoscopic thyroidectomy, although less
      severe than after open methods, is still a source of marked discomfort and
      surgical stress. This clinical trial was conducted to determine if repeated
      intravenous paracetamol could decrease postoperative pain and rescue analgesic
      requirements after robot-assisted endoscopic thyroidectomy via the transaxillary
      approach. MATERIALS AND METHODS: This prospective, randomized, double-blinded,
      and placebo-controlled study enrolled 124 women 21-60 years of age who were
      scheduled for elective gasless robot-assisted endoscopic thyroidectomy via the
      transaxillary approach. The patients were given placebo or 1 g of paracetamol as
      a 100 ml solution infused over 15 min 1 h before the induction of anesthesia, and
      then at 6-h intervals for the following 24 h. RESULTS: Postoperative pain scores
      were significantly lower at 1, 3, 6, and 24 h after surgery in the paracetamol
      group than in the placebo group. Significantly fewer patients in the paracetamol
      group received rescue analgesics compared to the placebo group (9.5% vs. 65.6%,
      respectively). First analgesic time was similar in the two groups. Postoperative
      nausea (44.3% vs. 22.2%) and vomiting (21.3% vs. 6.3%) were more frequent in the
      placebo group than in the paracetamol group. Other postoperative side effects,
      including sedation, confusion, and pruritus, were similar in the two groups.
      CONCLUSIONS: We concluded that repeated administration of 1 g of intravenous
      paracetamol over 24 h is easy, effective, safe, and well tolerated for pain
      management in patients with moderate to severe postoperative pain after gasless
      robot-assisted endoscopic thyroidectomy performed via the transaxillary approach.

PMID- 20054545
TI  - Structured ultrasonography workshop for breast surgeons: is it an effective
      training tool?
AB  - BACKGROUND: Effective training is essential to ensure satisfactory performance in
      surgeon-performed ultrasonography (US) and guided breast needle biopsies (USGBB).
      This study aimed to determine the efficacy of conducting a structured workshop in
      the teaching of breast US application and in guided biopsy techniques. METHODS:
      Consenting participants of the US for Surgeons Workshop at the General Surgeons
      Australia 2008 Annual Scientific Meeting were recruited. The workshop was divided
      into theoretical and practical components. For the theoretical component, brief
      pretests were administered, followed by lecture series, and then posttests. For
      the practical component, preinstructional USGBBs performed on breast phantoms and
      turkey breasts implanted with simulated lesions were assessed, followed by
      tutorials; it was concluded with postinstructional biopsy assessment. Points were
      deducted for simulated chest wall hits (complications). Previous experience and
      training in USBGG were recorded. Pre- and postlecture/instructional results were
      compared and the correlation tested using Student's t-test (p < 0.05). RESULTS:
      In all, 14 participants were recruited: 71% had no to moderate experience with
      USGBB. For the theoretical component, 33% improvement over the pretest (p <
      0.001) was seen across all levels of experience. For the practical component,
      there was 56% improvement after instruction (p = 0.001), which was most marked in
      the moderate experience group (83%, p = 0.03). Two complications were recorded
      for the least experienced group prior to instructions, but no complications were
      seen following instructions. CONCLUSIONS: Structured workshops are effective for
      training surgeons in US application and USGBB and should be considered as part of
      standardized training guidelines and credentialing. Theory and practical
      components demonstrated similar efficacy and should be considered integral
      components in training programs. Formal training decreases complication rates,
      especially among the inexperienced.

PMID- 20054546
TI  - Refractory cystobiliary fistula secondary to percutaneous treatment of hydatid
      cyst: treatment with N-butyl 2-cyanoacrylate embolization.
AB  - A 27-year-old female with a type 2 hydatid cystic lesion in the liver according
      to the Gharbi classification (CE 3A according to the WHO classification) was
      referred for percutaneous treatment after albendazole treatment for 1 year. A
      catheterization technique was performed but hypertonic saline and alcohol were
      not given into the cavity due to cystobiliary leakage. During the 4-month follow
      up period, sequential cavitography revealed biliary fistula, and bile-stained
      drainage had not been ceased despite the sphincterotomy, nasobiliary drainage
      catheter, and plastic stent. Since the patient refused to surgery, we embolized
      the biliary fistula using N-butyl 2-cyanoacrylate for the first time in the
      literature. At the 3-month follow-up, the patient's course was uneventful and
      ultrasound, multidetector-row CT, and MRI examinations revealed no collection in
      or adjacent to the cavity.

PMID- 20054547
TI  - Acquired haemophilia caused by non-haemophilic factor VIII gene variants.
AB  - The aetiology of anti-factor VIII (FVIII) autoantibody formation in acquired
      haemophilia remains unknown. We hypothesised that encounter of antigenically
      different, allogeneic FVIII may challenge inhibitor formation after presentation
      on MHC class II. Eighteen consecutive cases with acquired haemophilia were
      enrolled (nine females, nine males). A control group comprised 50 male and 50
      female healthy blood donors. The coding region of the FVIII gene and the HLA-DRB1
      genotype were studied. The presentation of foreign FVIII variants on the
      patient's MHC class II alleles was predicted using SYFPEITHI algorithm. A rare
      FVIII variant (E2004K) was found in one patient with acquired haemophilia after
      massive transfusion; the 2004 K allele was predicted to be presented on the
      patient's HLA-DRB1*0101. Moreover, distribution of a polymorphism (D1241E) was
      significantly skewed comparing patients and controls. Three of three patients
      with transfusion-associated disease carried 1241D in homozygous or hemizygous
      form and were predicted to present 1241E (foreign), but not 1241D (self), on
      their HLA-DRB1*0301. Therefore, encounter of 1241E may result in the presentation
      of a new T cell epitope in these patients. The same conditions were not found in
      any patient with acquired haemophilia of other causes. The expected frequency in
      the general Caucasoid population undergoing transfusion is 3% to 4%. In
      conclusion, encounter of variant allogeneic FVIII presented on a suitable MHC
      background could be a risk factor for inhibitor formation.

PMID- 20054548
TI  - Shedding of the endothelial receptor tyrosine kinase Tie2 correlates with
      leukemic blast burden and outcome after allogeneic hematopoietic stem cell
      transplantation for AML.
AB  - Angiogenesis plays an important role in the growth and viability of hematologic
      malignancies. Emerging data suggest a crucial involvement of the endothelial
      specific Tie2 receptor and its antagonistic ligand Angiopoietin-2 (Ang-2) in this
      process. The purpose of this study was to elucidate whether the soluble domain of
      the Tie2 receptor (sTie2)predicts outcome in patients with acute myeloid
      leukemia(AML) undergoing allogeneic hematopoietic stem cell
      transplantation(HSCT). Serum levels of sTie2 and Ang-2 were measured by ELISA in
      181 AML patients before conditioning for HSCT. The median follow-up time was 22
      months after HSCT. Pre-HSCT sTie2 levels were significantly higher inpatients
      (median 2.2 (range 1.8-3.0) ng/mL) compared to healthy controls (1.3 (0.9-1.6);
      p<0.0001). Elevated sTie2 levels were independently associated with active AML
      but did not relate to cytogenetics/mutational status before transplantation.
      Logistic regression analysis identified elevated sTie2 (odds ratio (OR) 3.07 (95%
      confidence interval(CI; 1.56-6.04), p=0.001) as a strong predictor for disease
      relapse and poor overall survival after HSCT. In a multimarker approach the
      highest risk for relapse was observed inpatients with both elevated sTie2 and
      elevated Ang-2 (OR 4.07, (95% CI 1.79-9.25) p<0.0001), as well as patients with
      both elevated Ang-2 and elevated bone marrow blast count (OR 4.16, (95% CI 1.88
      7.36) p<0.0001). Elevated serum sTie2 levels were related to active
      leukemia,correlated with the percentage of leukemic blasts in the bone marrow,
      and independently predicted relapse in AML patients after allogeneic HSCT.
      Furthermore, our data indicate that Tie2 shedding and Ang-2 release seem to
      reflect overlapping, but nevertheless distinctive features in leukemia-associated
      neoangiogenesis.

PMID- 20054549
TI  - A phase-I trial of pemetrexed plus carboplatin in recurrent ovarian cancer.
AB  - BACKGROUND: Carboplatin-based combinations are established in platinum-sensitive
      recurrent ovarian cancer. To improve the therapeutic index, new platinum-based
      combinations are required. Pemetrexed is a multi-targeted antifolate inhibiting
      thymidylate synthase. The aim of this study was to determine the maximally
      tolerated dose (MTD) and dose-limiting toxicity (DLT) and to characterize
      toxicities of the combination of pemetrexed (Pem) and carboplatin (Cb). DESIGN: A
      standard three-patient cohort dose escalation was performed starting at Cb AUC-5
      and Pem 500 mg/m(2). Patients with platinum-sensitive recurrent ovarian cancer
      were eligible. Two levels of Cb (AUC-5, 6) and five levels of Pem (500, 600, 700,
      800, and 900 mg/m(2)) were evaluated. DLTs were based on cycle 1. RESULTS: Twenty
      patients were enrolled. The median age was 57.4 years (37.3-75.3) and the median
      platinum-free interval was 26.2 months (7.2-124.4). There was one DLT at dose
      level 3 in cycle one. No serious adverse events related to the study therapy were
      observed. The 20 patients completed 112 cycles of Cb (104 were planned) and 115
      cycles of Pem (112 were planned). The maximum dose level of Cb AUC-6 and Pem 900
      mg/m(2) was well tolerated. Response rates in 19 patients were: CR: 63.2%; PR:
      21.1%; SD; 5.3%, PD: 10.5%. CONCLUSIONS: The combination carboplatin and
      pemetrexed is safe and well tolerated. A multicenter phase-II trial is currently
      underway.

PMID- 20054550
TI  - A free boundary problem modeling thrombus growth: model development and numerical
      simulation using the level set method.
AB  - Recently, neglect of either shear stress, surface saturation, or thrombus growth
      in mathematical models of platelet deposition has been identified as leading
      cause of inability to match experimental evidence. While the consideration of
      shear stress is necessary to obtain at least some qualitative agreement, purely
      shear-dependent approaches yield notable quantitative discrepancies. In a
      previous paper, the author demonstrated that surface saturation significantly
      improves model predictions. However, discrepancies still persist when thrombus
      growth is neglected. Therefore, the present work develops a free boundary problem
      which takes this into account. Numerical simulations are performed using the
      level set method. The results agree well with measurements in stagnation point
      flow and tubular expansions, which demonstrates the coupling of flow, platelet
      adhesion, and aggregate growth in primary hemostasis.

PMID- 20054551
TI  - Heterologous expression of taro cystatin protects transgenic tomato against
      Meloidogyne incognita infection by means of interfering sex determination and
      suppressing gall formation.
AB  - Plant-parasitic nematodes are a major pest of many plant species and cause global
      economic loss. A phytocystatin gene, Colocasia esculenta cysteine proteinase
      inhibitor (CeCPI), isolated from a local taro Kaosiang No. 1, and driven by a
      CaMV35S promoter was delivered into CLN2468D, a heat-tolerant cultivar of tomato
      (Solanum lycopersicum). When infected with Meloidogyne incognita, one of root
      knot nematode (RKN) species, transgenic T1 lines overexpressing CeCPI suppressed
      gall formation as evidenced by a pronounced reduction in gall numbers. In
      comparison with wild-type plants, a much lower proportion of female nematodes
      without growth retardation was observed in transgenic plants. A decrease of RKN
      egg mass in transgenic plants indicated seriously impaired fecundity.
      Overexpression of CeCPI in transgenic tomato has inhibitory functions not only in
      the early RKN infection stage but also in the production of offspring, which may
      result from intervention in sex determination.

PMID- 20054552
TI  - Physiological roles of ERD10 in abiotic stresses and seed germination of
      Arabidopsis.
AB  - While screening for genes affected by cold, we found that Early Responsive to
      Dehydration 10 (ERD10)was induced by cold treatment. To further investigate the
      physiological functions of ERD10, we analyzed the T-DNA insertion mutant of ERD10
      as well as the expression of ERD10 in response to various stress conditions. The
      erd10 mutant showed reduced stress tolerance relative to wild-type plants.
      Activation of the CBF/DREB1 genes by cold stress did not occur in the erd10
      mutant, indicating that an increased level of ERD10 is required to subsequently
      activate the CBF/DREB1 genes and their downstream target genes during treatment
      with cold stress in Arabidopsis. In addition, we showed that accumulation of the
      ERD10 transcript in developing seeds was necessary for completion of seed
      development. Erd10 mutant seeds were abnormally shaped and showed reduced
      germination. These results suggest that ERD10 can play roles both in protection
      of the plants from various stresses, including cold and dehydration, and also in
      seed development and germination.

PMID- 20054553
TI  - Two instillations of epirubicin as prophylaxis for recurrence after transurethral
      resection of Ta and T1 transitional cell bladder cancer: a prospective,
      randomized controlled study.
AB  - BACKGROUND: Although transurethral resection (TUR) is the standard treatment for
      non-muscle-invasive bladder tumors, 40-80% of tumors recur in spite of complete
      resection. OBJECTIVE: To evaluate the efficacy, dose effectiveness and safety of
      early short-duration intravesical instillation therapy using epirubicin (EPI)
      administered immediately after TUR and on the next day following TUR. PATIENTS
      AND METHODS: Between 1995 and 2001, 303 patients with Ta and T1 non-muscle
      invasive bladder carcinoma were enrolled in this study. Patients were randomized
      into three groups. Group A patients were treated with two intravesical infusions
      of EPI 20 mg/40 ml saline immediately after TUR and within 24 h. Group B patients
      were treated with EPI 50 mg/100 ml on the same schedule as group A. Group C
      patients were treated by TUR alone as a control group. The primary endpoint was a
      duration to the first recurrence. RESULTS: Of the 303 patients, 79 in Group A, 84
      in Group B, and 77 in Group C could be evaluated for recurrence. Median follow-up
      was 44 months. Median recurrence-free survival durations for Groups A, B, and C
      were 24, 38, and 13 months, respectively. The difference between Groups B and C
      was statistically significant (p = 0.04). Adverse reactions related to
      instillation were observed in about 30% of the patients. These reactions included
      micturition pain and frequency. These toxicities were mild and transient.
      CONCLUSION: Intravesical instillation of EPI 50 mg twice within 24 h after TUR
      was effective as prophylactic therapy for non-muscle-invasive bladder cancer with
      tolerable toxicity problems.

PMID- 20054554
TI  - Level IIb lymph node metastasis in thyroid papillary carcinoma.
AB  - The objective of the study was to evaluate the incidence of level IIb lymph node
      metastases in neck dissections for thyroid papillary carcinoma (TPC) patients. 47
      neck dissections of 33 patients with TPC were prospectively evaluated. Selective
      neck dissections (levels II, III, IV, and V) were performed in all cases. If
      level I lymph node metastasis was suspected during the procedure, level I
      dissection was also performed. All level IIb specimens were sent separately from
      the remainder of the neck dissection for the pathological examination. The number
      of dissected and metastatic lymph nodes in each specimen was recorded. Twenty-two
      of 47 neck dissections (46.8%) were positive for the lymph node metastasis. Among
      47 neck dissection specimens, the incidence of lymph node metastasis at level II
      was 12.7% (6 of 47) and level IIb was 2.1% (1 of 47). The rate of level IIb lymph
      node involvement among patients with metastatic cervical lymph nodes was 4.5% (1
      of 22). The specimen with metastatic lymph node at level IIb had also metastasis
      at levels IIa, III, IV, and V. The results of the present study suggested that
      lymph node metastases in level IIb are rare in patients with TPC undergoing neck
      dissection.

PMID- 20054555
TI  - A medieval contribution to the history of legal medicine: the first European
      Necroscopic Registry.

PMID- 20054556
TI  - The relationship between visual function, duration and main causes of vision loss
      and falls in older people with low vision.
AB  - BACKGROUND: Falls are an alarming health problem and a major cause of injury
      among the elderly. The healthcare cost associated with falls is considerable.
      Visual acuity has been found to be an independent risk factor for falls; however,
      the results are not unanimous. Moreover, other aspects of visual function such as
      visual field, contrast sensitivity and depth perception have not been adequately
      investigated in relation to falls. The aim of this study, therefore, was to
      determine the relationship between visual function, duration, and main causes of
      visual impairment, and falls in individuals with low vision. METHODS: This was a
      cross-sectional study involving participants attending a public tertiary eye care
      hospital. Participants were mobile, aged 60 years or above, and had low vision
      (visual acuity >0.3 LogMAR in the better eye). Details about falls in the
      previous 12 months and other information were collected, and patients completed a
      questionnaire about activities of daily living. The duration and main causes of
      visual impairment, visual acuity, contrast sensitivity, depth perception, and
      visual field were assessed. Descriptive statistical analyses were performed to
      characterize the participants' sociodemographic and clinical data. RESULTS: One
      hundred and twenty seven patients (53%; 67 males) with a mean age of 76.3+/-8.3
      years were recruited. Thirty seven percent of the participants (n=47) had mild,
      50% (n=64) moderate and 13% (n=16) severe visual impairment (>0.3-0.5; >0.5-1.0;
      and >1.0 LogMAR respectively). The frequencies of single and multiple falls were
      42.5% and 12.6% respectively. Visual acuity, contrast sensitivity, depth
      perception, visual field, main cause, and duration of visual impairment were not
      significantly associated with falls (p>0.05). In multiple regression analyses,
      physical inactivity remained the only variable independently associated with
      falls in all models except for visual field. Overall, visually impaired people
      were three times more likely to fall if they were physically inactive.
      CONCLUSIONS: Visual function, duration and main causes of visual impairment are
      not independently associated with falls in people with low vision. However, a
      significant relationship between non-participation in physical activity and falls
      was found. Further work is required to investigate the association between vision
      related factors and falls in older people with visual impairment.

PMID- 20054559
TI  - Oral tongue squamous cell carcinoma: recurrent disease is associated with
      histopathologic risk score and young age.
AB  - PURPOSE: To apply the Brandwein-Gensler et al.'s histopathologic risk score (RS)
      system and to evaluate its impact on locoregional recurrence and overall survival
      in a series of cases of oral tongue cancer, along with variables of patient age
      and margin status. METHODS: Sections of the resection specimens (N = 50) were
      submitted to a RS assignment of three components: the worst pattern of invasion,
      lymphocytic infiltration and perineural invasion. Risk scores of 0-2 were
      classified as low-to-intermediate and RSs > or = 3 were classified as high with
      respect to recurrence and survival. Margins were considered as "clean" if the
      tumor was > or = 5 mm away from them, otherwise they were defined as "positive".
      Patients < or = 60 years were considered "young" and those >60 years "old".
      Kaplan-Meier survival analysis with univariate and Cox multivariate regression
      model with stepwise forward selection tests were used. RESULTS: Univariate
      analysis showed that locoregional recurrence was negatively influenced by high
      RSs (P = 0.011), "young" age (P = 0.027) and positive margins (P = 0.027).
      Multivariate analysis revealed that the risk of recurrence was increased by high
      RSs (hazard ratio 11.14; P = 0.022) and "young" age (hazard ratio 3.41; P =
      0.022). "Young" patients with high RSs had a higher frequency of recurrence rate
      compared to "young" patients with low-to-intermediate scores (P = 0.008) and
      "old" patients with low-to-intermediate and high RSs (P = 0.012 and P = 0.011,
      respectively). CONCLUSIONS: The histopathologic RS can serve to identify a
      subgroup of patients <60 years who have a high recurrence rate of oral tongue
      cancer, irrespective of the margin status.

PMID- 20054560
TI  - Increased expression of cellular retinol-binding protein 1 in laryngeal squamous
      cell carcinoma.
AB  - PURPOSE: To investigate the genomic alterations in larynx carcinomas (LaCa)
      tissues and its prognostics values in predicting survival. METHODS: To analyse
      the aberrations in the genome of LaCa patients, we used array comparative genomic
      hybridization in 19 human laryngeal tumour samples. DNA samples were also
      subjected to detect human papillomavirus (HPV) sequences by polymerase chain
      reaction (PCR). Copy number gain was confirmed by real-time PCR. The cellular
      retinol-binding protein 1 (CRBP-1) gene expression was also confirmed by
      immunohistochemistry assay on LaCa tissues. To identify prognostic feature, CRBP
      1 gene gain was correlated to patient survival. RESULTS: The most common gains
      were detected for CRBP-1 and EGFR genes, while DNA lost in RAF-1 gene.
      Immunohistochemistry assay was revealed strong expression of CRBP1 protein in
      those cases with CRBP-1 gene gain. The CRBP-1 gene gain and its expression
      correlated significantly with survival (P = 0.003). Cox regression analysis
      indicated that CRBP-1 expression level was a factor of survival (P = 0.008). HPV
      sequences were detected in 42% of the samples, and did not show any relationship
      with specific gene alterations. CONCLUSION: Our data shows that CRBP-1 gene gain
      can be determined by immunohistochemistry on routinely processed tissue
      specimens, and could support as a potential novel marker for long-term survival
      in laryngeal squamous cell carcinoma.

PMID- 20054561
TI  - Molecular characterization of Giardia duodenalis  isolates from domestic ferrets.
AB  - Giardia duodenalis is a pathogen that has been found in a variety of mammals,
      including humans, and consists of host-specific (assemblages C, D, E, F, and G)
      and zoonotic (assemblages A, B) genetic groups. Ferrets are popular pets, and
      they, like humans, are hosts to this pathogen. The genetic characteristics of the
      Giardia population in ferrets are unclear because only one ferret isolate has
      been genotyped. To develop a more complete picture of the genetic characteristics
      of the Giardia population in domestic ferrets two additional Giardia isolates,
      recovered independently from two ferrets suffering from intestinal or hepatic
      giardiasis, were analyzed genetically. The sequences of both isolates at three
      loci, small subunit ribosomal RNA (SSUrDNA, 292 bp), beta-giardin (734 bp), and
      glutamate dehydrogenase (GDH, 713 bp) were identical to each other, but the
      sequences of triosephosphate isomerase locus (TPI, 512 bp) had five substitutions
      between isolates. Sequence homology and phylogenetic analyses at four loci
      identified both isolates as members of the assemblage A. Moreover, the sequences
      of SSUrDNA, beta-giardin, and GDH from both isolates were identical to those of
      the previous ferret isolate genotyped as assemblage A within the regions of
      overlap. The result obtained in the present study indicates that at least two
      genetically different types in assemblage A exist in domestic ferrets. In
      addition, there have been no reported human and animal isolates with the same
      sequence as those from ferret isolates at all four loci examined, suggesting that
      the present ferret isolates might be host-specific.

PMID- 20054562
TI  - Repellency against head lice (Pediculus humanus capitis).
AB  - The head louse problem increases at all levels of the international societies due
      to activities or life conditions that lead to often hair contacts among people.
      Lice occur exclusively on humans. Thus, they avoid dropping down from a head and
      therefore accept even a bad smelling hair of new a host. Due to this behaviour,
      there are only a few products on the markets which dare to claim a repellency
      activity that protects humans from infestation with head lice. The present study
      shows that a combination of an extract of the seeds of the plant Vitex agnus
      castus (monk pepper) and the compound paramenthan-3,8-diol (which is also found
      in some plants, e.g. Eucalyptus) act synergistically and are able to protect
      human hair for at least 7 h from invasion of head lice (Pediculus humanus
      capitis). The recently developed product containing both compounds is named
      Licatack Preventive Spray.

PMID- 20054563
TI  - Selenium supplementation at low doses contributes  to the antioxidant status in
      Trichinella spiralis-infected rats.
AB  - Selenium (Se) supplementation may prevent the formation of free radicals and
      lipid peroxidation processes in trichinellosis. The oxidative-antioxidant status
      of male Wistar rats infected or uninfected with Trichinella spiralis (Nematoda)
      and supplemented or unsupplemented with Sel-plex (Alltech) was tested through
      blood biomarkers. Sel-plex was applied to restore antioxidant defense system. The
      oxidative marker was malondialdehyde (MDA) concentration. The antioxidant markers
      were superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and
      concentrations of Se and vitamin E. The animals were allocated into four groups.
      The experiment covered 8 weeks post infection. A mathematical model was proposed
      for the time course of host body weight. The model solutions were in good
      agreement with the experimental data. The relative rates of body weight gain were
      determined as growth kinetic parameters. The supplementation of the rats with
      dietary Se improved their antioxidant status. Increases by 10% in SOD activity,
      6% in GPx activity, 13% in vitamin E concentration, 17% in plasma Se
      concentration, and 19% in liver Se concentration, respectively, and a decrease by
      18% in serum MDA concentration were recorded in the infected and supplemented
      towards infected and unsupplemented rats. The reduction of muscle larvae after
      Sel-plex application was 63%. The mortality in infected and uninfected animals
      did not differ significantly. No statistically significant differences were
      established between the growth of the control and infected rats. At week 8, the
      body weight gain in the supplemented rats (both uninfected and infected) was 30%
      higher, compared to that in unsupplemented ones. Diet with Se could be beneficial
      in the treatment of diseases correlated with considerable oxidative stress,
      particularly parasitoses.

PMID- 20054564
TI  - Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23
      22.3.
AB  - Autosomal recessive hypotrichosis is a rare form of human genetic disorder
      characterized by sparse to absent hair on scalp and rest of the body of affected
      individuals. Over the past few years at least five autosomal recessive forms of
      hypotrichosis loci have been mapped on different human chromosomes. In the
      present study, we report localization of another novel autosomal recessive
      hypotrichosis locus on human chromosome 10q11.23-22.3 in a four generation
      consanguineous Pakistani family. All the four patients in the family showed
      typical features of hereditary hypotrichosis including sparse hair on the scalp
      and rest of the body. Human genome scan using highly polymorphic microsatellite
      markers mapped the disease locus to a large region on chromosome 10. This novel
      locus maps to 29.81 cM (28.5 Mb) region, flanked by markers D10S538 and D10S2327
      on chromosome 10q11.23-22.3. A maximum multipoint LOD score of 3.26 was obtained
      with several markers in this region. DNA sequence analysis of exons and splice
      junction sites of four putative candidate genes (P4HA1, ZNF365, ZMYND17, MYST4),
      located in the linkage interval, were sequenced but were negative for functional
      sequence variants.

PMID- 20054565
TI  - Incisions do not simply sum.
AB  - BACKGROUND: Critics of minimally invasive methods sometimes argue that the summed
      lengths of all trocar sites have a morbidity similar to that for an open incision
      of equal length. This argument assumes correctly that pain and scarring are
      proportional to the total tension normal to a linear incision. But the argument
      also assumes that total tension sums linearly with incision length. This report
      demonstrates why that premise is not valid. METHODS: Wounds of various sizes are
      compared using a simple mathematical model. The closing tension perpendicular to
      any linear incision is a function of the incision's length, varying symmetrically
      together with a maximum at the midpoint of length. If tension rises linearly
      across an incision, integration of the tension relationship demonstrates that the
      total wound tension actually is proportional to the square of the length. In this
      report, incisions of various lengths are modeled, and plausible alternative
      incision scenarios for various procedures (e.g., Nissen, appendectomy) are
      compared. RESULTS: Total tension rises nonlinearly with increasing wound length.
      Thus, total tension across multiple incisions is always less than the total
      tension for an incision of the same total length. For example, an open
      appendectomy creates 2.7-fold more wound tension than a laparoscopic
      appendectomy. Similarly, two 3-mm trocars create less total tension than a single
      5-mm trocar. CONCLUSION: Conventional incisions are subject to more total tension
      than any combination of trocar incisions of equal total length. This inequality
      yields three clinically relevant corollaries. First, it supports the practice of
      using the smallest effective trocars (or even no-trocar methods) to minimize pain
      and scar. Second, addition of a trocar in difficult cases adds relatively little
      morbidity. Finally, using two small trocars is better than using a single larger
      trocar.

PMID- 20054567
TI  - Raising the technology bar in minimally invasive surgery: look how far we've
      come.

PMID- 20054568
TI  - Thresholds and combined quality control in the multimodal treatment of colorectal
      cancer.

PMID- 20054569
TI  - Laparoscoendoscopic single-site cholecystectomy and occult gallbladder cancer.

PMID- 20054570
TI  - Laparoscopic radical cholecystectomy and Roux-en-Y choledochojejunostomy for
      gallbladder cancer.
AB  - BACKGROUND: Although laparoscopic cholecystectomy was one of the first
      laparoscopic procedures, gallbladder cancer has been one of the last malignancies
      tackled with minimally invasive techniques. This video reviews the minimally
      invasive approaches to preoperatively suspected gallbladder cancer. METHODS: Like
      the standard laparoscopic cholecystectomy, the minimally invasive procedure is
      performed with four trocars. The surgeon operates with the patient in the French
      position. A totally laparoscopic radical cholecystectomy including wedge
      resections of segments IVB and V is undertaken with hepatoduodenal
      lymphadenectomy and common bile duct excision. The biliary system is
      reconstructed via a laparoscopic choledochojejunostomy. RESULTS: Six patients
      have undergone laparoscopic radical cholecystectomy. Three of these patients were
      found to have gallbladder cancer according to the final pathology. All the final
      surgical margins were negative, and the average lymph node retrieval was 3
      (range, 1-6). CONCLUSION: The minimally invasive approach to gallbladder cancer
      is feasible and safe. It should currently be performed in high-volume centers
      with expertise in both hepatobiliary and minimally invasive surgery. Larger
      trials are needed to determine whether either the open or laparoscopic approach
      offers any advantage.

PMID- 20054571
TI  - Video. Transanal single-port low anterior resection in a cadaver model.
AB  - BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES), a recent
      development in the field of minimally invasive surgery, provides theoretical
      advantages over open and laparoscopic surgery. Challenges with the use of NOTES
      for colon resections include the need to extract a large specimen and perform an
      intestinal anastomosis. A transanal single-port laparoscopic proctectomy uses the
      potential advantages of NOTES yet provides easy specimen extraction and
      anastomosis. METHODS: Fresh frozen then thawed human cadavers were used. Access
      was obtained via transanal mucosectomy, and a transanal endoscopic microsurgery
      (TEM) system was used to perform the proctectomy once the procedure was above the
      pelvic floor. After the peritoneal cavity was entered, a hand port was placed
      through the sphincter and above the pelvic floor. The left colon was mobilized
      using two 5-mm working ports and a 10-mm camera port for the flexible-tipped
      laparoscope that were placed through the hand port. The specimen was removed
      transanally. RESULTS: The critical steps for an oncologic resection of the rectum
      were achieved using a combination of TEM and laparoscopic instrumentation
      transanally. The rectum and mesorectum were mobilized. The left ureter was
      identified and preserved, the inferior mesenteric artery (IMA) ligated at its
      origin, the inferior mesenteric vein ligated near the ligament of Treitz, the
      proximal colon mobilized for transanal extraction, the specimen resected proximal
      to the ligated IMA, and a hand-sewn coloanal anastomosis performed. Postresection
      examination showed preservation of the hypogastric nerves and an intact
      mesorectum. Challenges included maneuverability around the sacral promontory and
      length of the instruments. However, this was easily overcome by the use of long
      reticulating instruments and a flexible-tipped laparoscope. CONCLUSIONS:
      Transanal single-port low anterior resection using TEM and laparoscopic
      techniques is feasible and can maintain the principles of an oncologic resection.

PMID- 20054573
TI  - Long-term follow-up evaluation of chronic pain after endoscopic total
      extraperitoneal repair of primary and recurrent inguinal hernia.
AB  - BACKGROUND: Long-term data on chronic pain after endoscopic total extraperitoneal
      (TEP) hernia repair are hardly available. METHODS: Between January 1997 and
      December 1998, 416 patients with consecutive primary and recurrent inguinal
      hernia underwent endoscopic TEP hernia repair. Long-term follow-up evaluation was
      carried out from June 2007 to June 2008. The primary outcome measure was
      persistent pain and discomfort interfering with daily activity. RESULTS: The
      overall response rate was 66% (273 of 416 patients). Of the 416 patients, 85
      (20%) had died of causes unrelated to hernia repair and 58 (14%) were lost to
      follow-up. A total of 177 patients were physically examined in the outpatient
      clinic. Because 96 patients were not able to visit the outpatient' clinic, they
      completed the survey by telephone. The median follow-up period was 10 years
      (range, 9-11 years). After TEP repair, 16 patients (6%) reported chronic groin
      pain, and 10 patients (4%) still experience pain at this writing after the 10
      year follow-up period. One of the patients has experienced persistent pain and
      discomfort interfering with daily activity. Patients with preoperative pain have
      reported significantly more chronic pain (P = 0.03). CONCLUSIONS: Chronic groin
      pain after TEP repair of primary and recurrent inguinal hernia seems to have a
      low incidence after a 10-year follow-up period.

PMID- 20054574
TI  - Alterations in portal vein blood pH, hepatic functions, and hepatic histology in
      a porcine carbon dioxide pneumoperitoneum model.
AB  - BACKGROUND: Intra-abdominal high pressure and acidosis by carbon dioxide (CO(2))
      pneumoperitoneum is known to affect various organ functions. In this study,
      changes in liver functions and liver histology were investigated during CO(2)
      pneumoperitoneum in a large animal model. METHODS: Fourteen white pigs were
      anesthetized with intubation and controlled ventilation. The pigs in the
      pneumoperitoneum group (PG) were exposed to CO(2) pneumoperitoneum at an intra
      abdominal pressure of 8 mmHg, and those in the open laparotomy group (OG) were
      subjected to laparotomy. Hemodynamics were measured and liver function tests were
      performed in the carotid artery and portal vein, and the liver tissue was
      histologically examined. RESULTS: The blood pressure, PO(2), PCO(2), and pH in
      the carotid artery did not significantly differ between the groups. In the PG,
      blood pressure, PO(2), and PCO(2) in the portal vein were elevated while the pH
      was low. There were no significant differences in the levels of aminotransferases
      and lactate between the groups. In the PG, the arterial ketone body ratio (AKBR)
      was low at 90 min and the ICG retention rate was high at 180 min; these values
      differed significantly compared to those at 0 min. Histological examination
      revealed liver congestion in the PG and no significant change in the OG. In the
      PG, the TUNEL assay revealed positive staining in the area with focal lytic
      changes. CONCLUSIONS: CO(2) pneumoperitoneum at an intra-abdominal pressure of 8
      mmHg in a porcine model affected liver functions and caused histological changes
      in the liver. Although it is uncertain whether these alterations observed in the
      porcine liver occur in humans as well and whether the alterations are reversible
      after pneumoperitoneum, it may be necessary to pay attention to liver damage
      during laparoscopic surgery.

PMID- 20054576
TI  - Sentinel lymph node mapping by colonic tattooing: reply.

PMID- 20054575
TI  - EAES recommendations on methodology of innovation management in endoscopic
      surgery.
AB  - BACKGROUND: Under the mandate of the European Association for Endoscopic Surgery
      (EAES) a guideline on methodology of innovation management in endoscopic surgery
      has been developed. The primary focus of this guideline is patient safety,
      efficacy, and effectiveness. METHODS: An international expert panel was invited
      to develop recommendations for the assessment and introduction of surgical
      innovations. A consensus development conference (CDC) took place in May 2009
      using the method of a nominal group process (NGP). The recommendations were
      presented at the annual EAES congress in Prague, Czech Republic, on June 18th,
      2009 for discussion and further input. After further Delphi processes between the
      experts, the final recommendations were agreed upon. RESULTS: The development and
      implementation of innovations in surgery are addressed in five sections: (1)
      definition of an innovation, (2) preclinical and (3) clinical scientific
      development, (4) scientific approval, and (5) implementation along with
      monitoring. Within the present guideline each of the sections and several steps
      are defined, and several recommendations based on available evidence have been
      agreed within each category. A comprehensive workflow of the different steps is
      given in an algorithm. In addition, issues of health technology assessment (HTA)
      serving to estimate efficiency followed by ethical directives are given.
      CONCLUSIONS: Innovations into clinical practice should be introduced with the
      highest possible grade of safety for the patient (nil nocere: do no harm). The
      recommendations can contribute to the attainment of this objective without
      preventing future promising diagnostic and therapeutic innovations in the field
      of surgery and allied techniques.

PMID- 20054577
TI  - Endoscopic full-thickness resection of gastric lesions using a novel grasp-and
      snare technique: evaluation in a porcine survival model.
AB  - BACKGROUND: Endoscopic full-thickness resection (EFTR) is a less-invasive method
      of en bloc removal of gastrointestinal tumors. In a previous nonsurvival animal
      experiment, the feasibility of a novel grasp-and-snare EFTR technique using a
      prototype tissue-lifting device was demonstrated. The objective of this study was
      to evaluate the safety and outcomes of this EFTR method in a porcine survival
      model. METHODS: EFTR of model stomach tumors was performed in seven pigs using a
      double-channel endoscope with a prototype tissue-lifting device through one
      channel and snare through the other. The lifting device was advanced through the
      snare loop and anchored to the gastric wall adjacent the model tumor. The lifting
      device was then partially retracted into the endoscope, causing the target
      tissue, including tumor, to evert into the gastric lumen. The open snare was then
      placed beyond the tumor around uninvolved gastric tissue. Resection was performed
      by delivering an electrosurgical current through the snare. EFTR defects were
      closed by using tissue anchors. After an intended 10-day observation period, the
      pigs were euthanized and necropsy was performed. RESULTS: All seven resections
      were successful with negative gross margins. No immediate complications occurred.
      Two defect closures failed during the early postoperative period, leading to
      infectious complications. The remaining intact closures were complicated by
      adjacent ulcers, one of which resulted in hemorrhage. CONCLUSIONS: Endoscopic
      full-thickness resection of gastric lesions using the grasp-and-snare technique
      is feasible in pigs. In this experiment, complications related to closure were
      significant. Further evaluation and modification of closure technique is
      necessary before studying this method of EFTR in humans.

PMID- 20054578
TI  - Differential regulation of MMP-2 in the gastrohepatic ligament of the
      gastroesophageal junction.
AB  - INTRODUCTION: Ligamentous attachments maintain the normal anatomic position of
      the gastroesophageal (GE) junction. Failure of these elastic ligaments through an
      alteration in collagen synthesis, deposition, and metabolism may be a primary
      etiology of hiatal hernia formation. Differential expression of zinc-dependent
      matrix metalloproteinases (MMPs) is largely responsible for collagen remodeling.
      The purpose of this study was to survey baseline levels of MMPs in supporting
      ligaments of the GE junction from patients without hiatal hernia. METHODS:
      Following an institutional review board-approved protocol, plasma and tissue
      biopsies of the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and
      phrenoesophageal ligament (PEL) were obtained in six patients without a hiatal
      hernia during laparoscopic anterior esophageal myotomy for achalasia. Total
      protein extracts from tissue biopsies were analyzed for elastases MMP-2, -9, and 
      12 and collagenases MMP-1, -3, -7, -8, and -13 using a multiplex profiling kit
      (R&D Systems, Minneapolis, MN). Data are reported as mean +/- standard deviation.
      Statistical significance (p < 0.05) was determined using Tukey's test and
      analysis of variance. RESULTS: In control patients without hiatal hernias,
      increased levels of MMP-2 (p < 0.02) were detected in the GHL compared with the
      GPL and PEL, respectively. Tissue levels of MMP-1, -12, and -13 were not
      detectable. CONCLUSIONS: Gelatinase-A (MMP-2) is present in the GHL and plasma of
      control patients. The GHL may provide the primary GE junction supporting ligament
      to compare tissue from patients with type I (sliding) and type III
      (paraesophageal) hiatal hernias to examine the role of altered collagen
      metabolism in hiatal hernia formation.

PMID- 20054579
TI  - Ten years of experience with resection of left-sided pancreatic ductal
      adenocarcinoma: evolution and initial experience to a laparoscopic approach.
AB  - BACKGROUND: With increasing laparoscopic experience, laparoscopic distal
      pancreatectomy with or without splenectomy is being regarded as a safe and
      effective treatment for benign and borderline malignant lesions of the pancreas;
      however, its application for left-sided pancreatic ductal adenocarcinoma (PDAC)
      is still debatable. METHODS: We analyzed patients who underwent conventional
      distal pancreatectomy with splenectomy (DPS) for distal pancreatic cancer at our
      institution. We have performed laparoscopic DPS partly based on radical antegrade
      modular pancreatosplenectomy (RAMPS) for well-selected left-sided PDAC since
      2007. We compared laparoscopic DPS to conventional DPS according to various
      clinicopathologic factors. RESULTS: From January 1999 to December 2008, 45
      patients underwent conventional DPS for resectable left-sided PDAC, and 18 needed
      combined adjacent organ resection for potential margin negative (R0) resection.
      The median survival of resected left-sided PDAC was 27.9 months with a 5-year
      survival of 28.9%. A small amount of intraoperative bleeding [< or =760 ml
      Exp(beta) = 6.312, p = 0.001] and R0 resection [Exp(beta) = 4.349, p = 0.090]
      were the most significant prognostic factors. To achieve bloodless and R0
      resection, the potential indication for laparoscopic DPS was suspicious
      pancreatic cancer confined to the pancreas that could be removed by DPS without
      resection of the adjacent organs. Five patients underwent laparoscopic/robot
      assisted DPS for left-sided PDAC. Compared to conventional DPS, only the
      operation time (p = 0.011) and tumor size (p = 0.031) were significantly
      different, but other clinicopathologic variables were comparable. All patients
      still are alive. Four patients have lived without tumor recurrence (follow-up = 4
      22 months), and only one experienced multiple liver metastasis and subsequent
      retroperitoneal local recurrence. CONCLUSION: Laparoscopic/robot-assisted
      modified anterior RAMPS may be technically feasible for well-selected PDAC. The
      oncologic feasibility still remains to be determined due to limited experience.

PMID- 20054580
TI  - Single-session endoscopic ultrasonography and endoscopic retrograde
      cholangiopancreatography for evaluation of pancreaticobiliary disorders.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) and endoscopic retrograde
      cholangiopancreatography (ERCP) often are required in the evaluation and
      treatment of patients with pancreaticobiliary disorders. Few reports of single
      session EUS-ERCP have raised questions regarding its safety and accuracy or about
      which procedure should be performed first. METHODS: Data from 2005 to 2009 were
      reviewed from a prospectively maintained EUS-ERCP database at a single tertiary
      care cancer center. Sensitivity and specificity of EUS and fine-needle aspiration
      (FNA), bile duct cannulation rate, duration of procedure, and complications were
      evaluated. RESULTS: Of the 35 patients (15 men and 20 women) studied, 28 had a
      final diagnosis of malignancy, and 7 had benign disorders. All the patients
      underwent ERCP and EUS, with FNA performed for 28 patients (80%). For 22 of the
      35 patients (62.8%), EUS was the first procedure performed. The sensitivity of
      EUS-FNA for malignancy was 96.4%. The bile duct cannulation rate during ERCP was
      97.1%. Five patients required a precut sphincterotomy for bile duct access, and
      one patient with chronic pancreatitis had a failed cannulation despite a EUS
      guided rendezvous. A stent was successfully placed in 29 patients (96%). No major
      complications occurred, and no contrast leak was seen when FNA was performed
      before the cholangiogram. One patient had periduodenal bleeding after FNA, which
      was managed conservatively. The mean duration of the procedure was 83.7 min.
      CONCLUSION: Single-session EUS-ERCP can be performed safely and with efficacy
      similar to that of the procedures performed separately.

PMID- 20054581
TI  - Diagnostic transgastric endoscopic peritoneoscopy: extension of the initial human
      trial for staging of pancreatic head masses.
AB  - BACKGROUND: The validity of natural orifice transluminal endoscopic surgery
      (NOTES) was confirmed in a human trial of 10 patients undergoing diagnostic
      transgastric endoscopic peritoneoscopy (DTEP) for staging of pancreatic head
      masses. This report is an update with 10 additional patients in the series and
      includes bacterial contamination data. METHODS: The patients in this human trial
      were scheduled to undergo diagnostic laparoscopy for abdominal staging of a
      pancreatic head mass. A second surgeon, blinded to the laparoscopic findings,
      performed a transgastric endoscopic peritoneoscopy (TEP). The findings of
      laparoscopic exploration were compared with that those of the TEP. Diagnostic
      findings, operative times, and clinical course were recorded. Bacterial
      contamination data were collected for the second cohort of 10 patients. Bacterial
      samples were collected from the scope before use and the abdominal cavity before
      and after creation of the gastrotomy. Samples were assessed for bacterial counts
      and species identification. Definitive care was rendered based on the findings
      from laparoscopy. RESULTS: In this study, 20 patients underwent diagnostic
      laparoscopy followed by DTEP. The average time for completion of diagnostic
      laparoscopy was 10 min compared with 21 min for TEP. The experience acquired
      during the initial 10 procedures translated to a 7-min decrease in TEP time for
      the second 10 cases. For 19 of the 20 patients, DTEP corroborated laparoscopic
      findings for surgical decision making. One endoscopic and five laparoscopic
      biopsies were performed. Pancreaticoduodenectomy was performed for 14 patients
      and palliative gastrojejunostomy for 6 patients. No cross-contamination of the
      peritoneum or infectious complications were noted. No significant complications
      related to either the endoscopic or laparoscopic approach occurred. CONCLUSIONS:
      This study supports the authors' previous conclusions that the transgastric
      approach to diagnostic peritoneoscopy is feasible, safe, and accurate. The lack
      of documented bacterial contamination further supports the use of this technique.
      Technical issues, including intraabdominal manipulation and gastric closure,
      require further investigation.

PMID- 20054582
TI  - Left laparoscopic paraduodenal hernia repair.
AB  - BACKGROUND: An internal hernia is a protrusion of bowel through a normal or
      abnormal orifice in the peritoneum or mesentery. Paraduodenal hernia is by far
      the most common form of congenital internal hernia, making up 53% of all reported
      cases. In recent years, as surgeons have become more comfortable with
      laparoscopic techniques, they are performing an increasing number of these
      procedures laparoscopically. METHODS: To highlight the technical steps of this
      technique, the case of a patient with a left paraduodenal hernia and a video of
      the laparoscopic repair are presented. Additionally, a PubMed search of the
      English medical literature was conducted using the search words "laparoscopic,"
      "paraduodenal," and "hernia" as filters. The cases of laparoscopic paraduodenal
      hernia repair in the literature to date recording data on technique,
      complications, and hospital course were reviewed. RESULTS: In addition to the
      case described in this report, 14 cases of laparoscopic paraduodenal hernia were
      described in 10 published reports. Of the 15 cases, 11 (73%) were left-sided,
      likely representing the relative incidence of these cases. The hernia defect was
      closed in 10 (77%) of the 13 cases for which the repair method was described,
      whereas the defect was widely opened in the remaining cases. One report described
      an operative complication (6.7%), an internal mesenteric vein injury, and one
      recurrence (6.7%) occurred 18 months after surgery in the direct defect closure
      group. CONCLUSION: The current data lead to the conclusion that laparoscopic
      paraduodenal hernia repair is a safe and feasible approach for selected patients.
      It can be expected that as surgeons become increasingly comfortable and facile
      with laparoscopic techniques, paraduodenal hernias and many other causes of acute
      small bowel obstruction will be increasingly managed laparoscopically.

PMID- 20054583
TI  - Impact of the patient's body position on the intraabdominal workspace during
      laparoscopic surgery.
AB  - BACKGROUND: The effects of the patient's body position on the intraabdominal
      workspace in laparoscopic surgery were analyzed. METHODS: The inflated volume of
      carbon dioxide was measured after insufflation to a preset pressure of 15 mmHg
      for 20 patients with a body mass index (BMI) greater than 35 kg/m(2). The
      patients were anesthetized with full muscle relaxation. The five positions were
      (1) table horizontal with the legs flat (supine position), (2) table in 20
      degrees reverse Trendelenburg with the legs flat, (3) table in 20 degrees reverse
      Trendelenburg with the legs flexed 45 degrees upward at the hips (beach chair
      position), (4) table horizontal with the legs flexed 45 degrees upward at the
      hips, and (5) table in 20 degrees Trendelenburg with the legs flat. The positions
      were performed in a random order, and the first position was repeated after the
      last measurement. Repeated measure analysis of variance was used to compare
      inflated volumes among the five positions. RESULTS: A significant difference in
      inflated volume was found between the five body positions (P = 0.042). Compared
      with the mean inflated volume for the supine position (3.22 +/- 0.78 l), the mean
      inflated volume increased by 900 ml for the Trendelenburg position or when the
      legs were flexed at the hips, and decreased by 230 ml for the reverse
      Trendelenburg position. CONCLUSIONS: The Trendelenburg position for lower
      abdominal surgery and reverse Trendelenburg with flexing of the legs at the hips
      for upper abdominal surgery effectively improved the workspace in obese patients,
      even with full muscle relaxation.

PMID- 20054584
TI  - Asymmetric cell division of rice zygotes located in embryo sac and produced by in
      vitro fertilization.
AB  - In angiosperms, a zygote generally divides into an asymmetric two-celled embryo
      consisting of an apical and a basal cell. This unequal division of the zygote is
      a putative first step for formation of the apical-basal axis of plants and is a
      fundamental feature of early embryogenesis and morphogenesis in angiosperms.
      Because fertilization and subsequent embryogenesis occur in embryo sacs, which
      are deeply embedded in ovular tissue, in vitro fertilization of isolated gametes
      is a powerful system to dissect mechanisms of fertilization and post
      fertilization events. Rice is an emerging molecular and experimental model plant,
      however, profile of the first zygotic division within embryo sac and thus origin
      of apical-basal embryo polarity has not been closely investigated. Therefore, in
      the present study, the division pattern of rice zygote in planta was first
      determined accurately by observations employing serial sections of the egg
      apparatus, zygotes and two-celled embryos in the embryo sac. The rice zygote
      divides asymmetrically into a two-celled embryo consisting of a statistically
      significantly smaller apical cell with dense cytoplasm and a larger vacuolated
      basal cell. Moreover, detailed observations of division profiles of zygotes
      prepared by in vitro fertilization indicate that the zygote also divides into an
      asymmetric two-celled embryo as in planta. Such observations suggest that in
      vitro-produced rice zygotes and two-celled embryos may be useful as experimental
      models for further investigations into the mechanism and control of asymmetric
      division of plant zygotes.

PMID- 20054586
TI  - Compressing the non-dependent lung during one-lung ventilation improves arterial
      oxygenation, but impairs systemic oxygen delivery by decreasing cardiac output.
AB  - PURPOSE: We have previously found that compression of the non-dependent lung
      improves arterial oxygenation during one-lung ventilation (OLV) in patients
      undergoing esophagectomy. The purpose of this study was to investigate the
      effects of compression of the non-dependent lung on hemodynamic indices and
      oxygen delivery using a minimally invasive cardiac output (CO) monitor. METHODS:
      Sixteen consecutive patients undergoing esophagectomy through a right thoracotomy
      were studied. Under general anesthesia, a left-sided double-lumen tube was placed
      for OLV, and the dependent lung was mechanically ventilated with a tidal volume
      of 8 ml kg(-1) body weight and a fraction of inspiratory oxygen of 0.8 during
      OLV. CO was monitored continuously using a FloTrac/Vigileo (Edwards Lifesciences)
      system. Surgeons compressed the non-dependent lung several times during surgery
      using a lung retractor to improve exposure of the surgical field. The oxygen
      delivery index was roughly estimated as the product of the cardiac index (CI) and
      arterial oxygen saturation as monitored by pulse oximetry (Spo2). RESULTS: Just
      before non-dependent lung compression, mean (+/- SD) CI and Spo2 were 2.6 +/- 0.6
      L min(-1) m(-2) and 95.0 +/- 3.9%, respectively. At 1 min after non-dependent
      lung compression, Spo2 increased significantly to 97.8 +/- 2.2% (P < 0.05), but
      CI decreased significantly to 2.0 +/- 0.4 L min(-1) m(-2) (P < 0.05). The product
      of CI and Spo2 at 1 min was significantly lower (192.7 +/- 37.3) than baseline
      levels (250.5 +/- 66.3, P < 0.05). CONCLUSION: Although non-dependent lung
      compression may be a potentially effective measure to treat hypoxemia during OLV,
      it should be noted that CO and systemic oxygen delivery may be decreased by this
      maneuver.

PMID- 20054587
TI  - Successful use of spinal anesthesia in a patient with severe Klippel-Trenaunay
      syndrome associated with upper airway abnormalities and chronic Kasabach-Merritt
      coagulopathy.
AB  - Klippel-Trenaunay syndrome is a rare disorder characterized by the triad of
      capillary or cavernous hemangiomas, venous varicosities or malformations, and
      soft tissue or bone hypertrophy. Neuraxial anesthesia in patients with Klippel
      Trenaunay syndrome has been infrequently described and has not been previously
      reported when accompanied by consumptive coagulopathy with thrombocytopenia
      (Kasabach-Merritt syndrome). The authors describe their clinical management of a
      23 year-old woman with Klippel-Trenaunay syndrome who presented for elective
      total knee arthroplasty. Her past medical history was notable for chronic
      Kasabach-Merritt syndrome, hypersplenism with pancytopenia, and intermittent
      lower gastrointestinal bleeding resulting from colonic hemangiomas. The physical
      examination revealed several large cavernous hemangiomas located on her right
      face, neck, chest, arm, and leg. No hemangiomas were noted within the dermatomal
      levels innervated by the upper lumbar spine. The neck hemangioma was very large
      and filled with blood when the patient assumed a supine position, making it
      almost impossible for her to breathe. The oropharynx revealed markedly
      hypertrophied soft tissue, pharyngeal, and hypopharyngeal hemangiomas, and a
      Mallampati class IV airway. Spinal and epidural hemangiomas were excluded based
      on a magnetic resonance imaging study before surgery. Kasabach-Merritt
      coagulopathy was corrected preoperatively by administration of cryoprecipitate.
      These interventions allowed the authors to safely perform a spinal anesthetic for
      the operation. The current case illustrates that major conduction anesthesia may
      be safely performed in patients with Klippel-Trenaunay disease provided that
      preoperative imaging studies exclude neurovascular involvement and coexisting
      coagulopathy is appropriately corrected.

PMID- 20054589
TI  - Structural characteristics of root-fungus associations in two mycoheterotrophic
      species, Allotropa virgata and Pleuricospora fimbriolata (Monotropoideae), from
      southwest Oregon, USA.
AB  - All members of the Monotropoideae (Ericaceae), including the species, Allotropa
      virgata and Pleuricospora fimbriolata, are mycoheterotrophs dependent on
      associated symbiotic fungi and autotrophic plants for their carbon needs.
      Although the fungal symbionts have been identified for A. virgata and P.
      fimbriolata, structural details of the fungal-root interactions are lacking. The
      objective of this study was, therefore, to determine the structural features of
      these plant root-fungus associations. Root systems of these two species did not
      develop dense clusters of mycorrhizal roots typical of some monotropoid species,
      but rather, the underground system was composed of elongated rhizomes with first-
      and second-order mycorrhizal adventitious roots. Both species developed mantle
      features typical of monotropoid mycorrhizas, although for A. virgata, mantle
      development was intermittent along the length of each root. Hartig net hyphae
      were restricted to the host epidermal cell layer, and fungal pegs formed either
      along the tangential walls (P. fimbriolata) or radial walls (A. virgata) of
      epidermal cells. Plant-derived wall ingrowths were associated with each fungal
      peg, and these resembled transfer cells found in other systems. Although the
      diffuse nature of the roots of these two plants differs from some members in the
      Monotropoideae, the structural features place them along with other members of
      the Monotropoideae in the "monotropoid" category of mycorrhizas.

PMID- 20054590
TI  - Taxonomic and functional characterisation of fungi from the Sebacina vermifera
      complex from common and rare orchids in the genus Caladenia.
AB  - The terrestrial orchid genus Caladenia contains many species which are threatened
      with extinction. They have highly specific associations with Sebacina vermifera
      and closely related fungi, and conservation of these terrestrial orchids, in
      part, relies on symbiotic propagation to produce plants for reintroduction and ex
      situ conservation collections. However, little is known of the diversity of
      mycorrhizal fungi associating with natural populations. Here, restriction
      fragment polymorphism analysis, internal transcribed spacer and nuclear large
      subunit sequencing and symbiotic seed germination were used to investigate the
      taxonomic and functional diversity of fungal isolates from single populations of
      six endangered Caladenia species and one common species across the same
      biogeographic range. Fifty-nine fungal isolates were collected for investigation
      including ten isolates from the six endangered species Caladenia audasii,
      Caladenia amoena, Caladenia sp. aff. fragrantissima (Central Victoria), Caladenia
      sp. aff. patersonii, Caladenia rosella and Caladenia orientalis and 49 isolates
      from six populations of the common species Caladenia tentaculata. While the
      common species associated with three distinct S. vermifera-like taxa, the six
      endangered species were restricted to one of these fungal taxa. No direct
      relationship between the taxonomic identity of the fungi and their ability to
      stimulate seed germination was observed; however, the majority of the fungi
      isolated from the Caladenia species were capable of germinating seed in vitro,
      indicating their mycorrhizal status and potential for symbiotic propagation in
      conservation programmes.

PMID- 20054591
TI  - Swine-origin H1N1 influenza A virus and dental practice:  a critical review.
AB  - Since the spring of 2009, there have been a considerable number of infected as
      well as fatal cases by virologically confirmed swine-origin H1N1 influenza A
      virus (S-OIV). The virus continues to spread globally. The World Health
      Organization (WHO) has now raised the level of S-OIV influenza pandemic alert to
      phase 6 ('the pandemic phase') because of the human-to-human transmission of the
      virus and the community-level outbreaks worldwide. The WHO also issues its
      concerns about the global surveillance, the diagnostic capacity for the infection
      and the pandemic preparedness plan in every country. However, no critical review
      on S-OIV influenza and dental practice published in the literature exists
      hitherto. Based on information up to November 2009, the aim of this article was
      to summarise significant data on this novel virus and a clinical practice
      guideline for dental professionals.

PMID- 20054592
TI  - Influence of ozone on the composite-to-composite bond.
AB  - The study evaluated the effect of ozone application on the composite-to-composite
      bond. Three hundred and twenty cylindrical composite specimens were divided into
      two groups: group 1 was subjected to a 60 s ozone application, whereas group 2
      remained untreated. Four subgroups were obtained from each group according to the
      intermediate repair agent: an adhesive, a silane, silane/adhesive combination, or
      flowable composite. Repair composite cylinders were built-up. The composite
      repair strength was tested after 24 h and after thermocycling with a shear test.
      Additionally, 4 mm * 4 mm * 2 mm composite specimens were prepared and stored 24
      h in deionized water. Half of the specimens were subjected to ozone application
      and the other served as control. The elastic modulus (E) and the Vicker's
      hardness (VH) of the composite surfaces were tested immediately and after
      thermocycling. Significant differences among the experimental groups were
      detected (p < 0.001). The composite repair strength was affected by the
      pretreatment and by the intermediate agent, whereas, the thermocycling was not
      significant. The partial eta-squared statistics showed that the intermediate
      agent was the main factor affecting the composite repair strength, whereas the
      pretreatment played a minor role. No differences were observed between ozone and
      control groups when the same intermediate agent and the same aging conditions
      were applied. Repairing with flowable composite tended to achieve higher bond
      strengths (20.7 and 26.5 MPa in ozone and control groups, respectively, after 24
      h). The use of silane coupling agent showed the lowest composite repair
      strengths. Ozone did not affect E and VH (p > 0.05) and the thermocycling
      affected only E (p < 0.05). In conclusion, the application of ozone does not
      impair the composite-to-composite bond.

PMID- 20054593
TI  - Comparative study of DFDBA in combination with enamel matrix derivative versus
      DFDBA alone for treatment of periodontal intrabony defects at 12 months post
      surgery.
AB  - The aim of this randomized double-blind, clinical trial was to compare the use of
      enamel matrix derivative (EMD) and demineralised freeze-dried bone allografts
      (DFDBA) with DFDBA alone for the treatment of human periodontal intrabony defects
      at 12 months post-surgery. Fifty-six intrabony osseous defects in 56 periodontis
      patients were randomly assigned to the test group (DFDBA + EMD) or the control
      group (DFDBA) for periodontal treatment. Clinical and radiographic measurements
      were made at the baseline and after 12 months. Compared to baseline, the 12-month
      results indicated that both treatment modalities resulted in significant changes
      in all clinical parameters (gingival index, bleeding on probing, probing depth
      (PD), clinical attachment level (CAL), gingival recession; P < 0.05) and
      radiographic parameters (hard tissue fill (HTF) and bone depth reduction; P
      <0.05). Furthermore, statistically significant differences were found in the test
      group compared to the control group in PD reduction (5.0 mm vs. 4.0 mm; P <
      0.05), CAL gain (4.0 mm vs. 3.25 mm), and HTF (4.0 mm vs. 3.5 mm; P < 0.05). In
      the test group, 25% of sites gained > 4 mm of CAL, while in the control group,
      7.1% of sites gained > 4 mm of CAL. Both treatments showed a good soft and hard
      periodontal tissue response. At 12 months post-surgery, the combined use of DFDBA
      and EMD seemed to produce a statistically significant improvement of PD
      reduction, CAL gain, and HTF.

PMID- 20054594
TI  - Interrelation between obesity, oral health and life-style factors among Turkish
      school children.
AB  - Obesity, dental caries and periodontal diseases are among major public health
      concerns which may affect children's growth and development. This study seeks any
      clustering between obesity, oral health and life-style factors among school
      children in Istanbul, Turkey. A cross-sectional study of children, 10- to 12-year
      olds, from a public and a private school was undertaken with questionnaires for
      children and their mothers and child oral health data, in Istanbul (n = 611).
      DMFS (number of decayed, missing and filled surfaces of permanent teeth), CPI
      (Community Periodontal Index), body mass index (BMI) and life-style factors
      (tooth-brushing frequency, milk consumption at breakfast and bedtimes on school
      nights) of children were examined. Data analysis included factor analysis,
      Student's t test and Chi-square tests by cross-tabulation. Public school children
      were more dentally diseased but less obese than were those in private school (P <
      0.001). They more frequently had calculus (62%) and reported non-recommended
      tooth-brushing (68%) than did those in private school (37%, 56%; P < 0.05).
      Principal component analysis revealed that DMFS, CPI and BMI shared the same
      cluster among all children. A need exists for addressing obesity, oral health and
      nutrition jointly in health promotion strategies to improve children's well-being
      and empower good life-style factors.

PMID- 20054595
TI  - Assessment of factors associated with dental caries in rural communities in Rakai
      District, Uganda.
AB  - To assess factors associated with dental caries in rural communities in Rakai
      District, Uganda. This was a cross-sectional survey in 18-62 year olds, randomly
      selected from three sub-counties: Kyalurangira (n = 121), Kabira (n = 133), and
      Kacheera (n = 67). The participants were clinically examined for caries using
      Decayed Missing Filled Teeth (DMFT) index and were administered to a structured
      questionnaire. In the whole material, caries prevalence (DMFT score > 0) was
      57.3% and the mean DMFT score was 2.3. The M-component contributed 61% of the
      DMFT scores. Using bivariate analyses, age, consumption of sugared snacks and
      tobacco smoking were directly and significantly associated with development of
      dental caries. Tooth cleaning and previous dental visits were indirectly and
      significantly associated with dental caries. In binary logistic regression
      analyses, the participants who were older were four times and those who consumed
      sugared snacks were 11 times more likely to develop dental caries as compared to
      their counterparts. The participants who cleaned their teeth or who had visited
      the dentists were less likely to develop dental caries as compared to their
      counterparts. The odds ratios were 0.6 and 0.5, respectively. Based on stepwise
      multiple linear regression analyses, age, previous dental treatment, consumption
      of sugared snacks, tooth cleaning and tobacco smoking explained a total of 46% of
      the variations in DMFT scores. Caries prevalence and severity were relatively low
      in this population. Although a number of independent variables were significantly
      associated with caries they gave a modest overall multivariate model.

PMID- 20054596
TI  - Abdominoscrotal hydrocele in a 9-month old infant.
AB  - Abdominoscrotal hydrocele represents an uncommon condition, especially in
      childhood, resulting from the communication of a large scrotal hydrocele with the
      abdominal cavity through the inguinal canal. The disorder has been associated
      with a variety of pathological entities such as hydronephrosis, lymphedema, and
      malignancy of the tunica vaginalis. Diagnosis is made by physical examination and
      confirmed by abdominal ultrasound scan. Surgical correction, although complex,
      remains the optimal therapeutic option. The present article reports the case of a
      9-month infant from Greece with abdominoscrotal hydrocele. Regardless of rarity,
      the disorder should be included in the differential diagnosis of scrotal and
      abdominal masses, as early diagnosis and surgical intervention may prevent the
      development of potential complications. The difficulty in establishing a
      preoperative diagnosis highlights the necessity for a physician to have a high
      level of familiarity with abdominoscrotal hydrocele and its possible
      complications. Awareness of this abnormality will ensure its prompt recognition
      and optimal management.

PMID- 20054597
TI  - Intraperitoneal onlay mesh: an experimental study of adhesion formation in a
      sheep model.
AB  - PURPOSE: Current hernia literature shows that the use of mesh in ventral hernia
      repair reduces the risk of recurrence significantly. In laparoscopic repair, the
      mesh is placed intraperitoneally. Accordingly, the close contact between mesh and
      viscera involves a risk of adhesion formation. In this experimental study, we
      examined the degree of de novo adhesion formation over time to currently
      available meshes. METHODS: Sixteen sheep each received laparoscopic placement of
      four (10 x 10 cm) meshes on intact peritoneum. Two different mesh materials
      (coated vs. non-coated) and two different fixation devices (absorbable/non
      absorbable) were investigated. (Parietex Composite, DynaMesh IPOM, ProTack and
      AbsorbaTack). After 3, 6, 12 and 18 months, four animals, respectively, underwent
      a new laparoscopy to determine the extent of adhesions to the mesh. RESULTS:
      Parietex Composite significantly reduced the formation of intraabdominal
      adhesions compared to DynaMesh IPOM. The mean extent of adhesions increases over
      time without reaching a steady state within the first 12 months after
      laparoscopic placement. CONCLUSIONS: This is the first long-term (18 months)
      experimental study on adhesion formation in sheep after laparoscopic placement of
      mesh and may serve as a template for future studies on meshes before marketing.

PMID- 20054598
TI  - Traumatic diaphragmatic hernia presenting as a tension fecopneumothorax.
AB  - A traumatic diaphragmatic hernia is a well-known complication following blunt
      abdominal or penetrating thoracic trauma. Although the majority of cases are
      diagnosed immediately, some patients may present later with a diaphragmatic
      hernia. It occurs in approximately 3% of abdominal traumas. Diagnosis requires a
      high index of suspicion since diaphragmatic injury can only reliably be ruled out
      by direct visualization, i.e., laparoscopy. Hence, delayed presentation with
      complications secondary to the injury is not uncommon. We discuss a case of a
      young man who presented in respiratory distress 5 years after a stab wound to the
      left chest. The patient was hypoxic, with a chest X-ray (CXR) demonstrating a
      pneumothorax with effusion. A chest tube was placed with a rush of air and
      feculent drainage. CT scan revealed an incarcerated transverse colon in a
      diaphragmatic hernia. The laparotomy demonstrated necrotic colon in the chest
      with gross fecal contamination in the chest. The diaphragmatic defect was closed
      and a Hartmann's procedure performed. The patient developed empyema in the
      postoperative period. Our patient is the twelfth reported case of a tension
      fecopneumothorax resulting from traumatic diaphragmatic herniation. This paper
      reviews all cases, including the diagnostic workup, operative approach, and
      expected postoperative course of this unusual condition.

PMID- 20054599
TI  - Isolated paralysis of glossopharyngeal and vagus nerve associated with type II
      occipital condyle fracture: case report.
AB  - INTRODUCTION: Occipital condyle fractures (OCFs) can occasionally be complicated
      with lower cranial nerve palsies. DISCUSSION: Isolated 9th and 10th cranial nerve
      palsies following OCF are very rare. To our knowledge, we report the first case
      of an early onset of 9th and 10th cranial nerve palsies with an early full
      recovery in short period of time and discuss the probable mechanism of isolated
      nerve palsy in the light of the relevant literature.

PMID- 20054600
TI  - Low expression of chemokine receptor CCR5 in human  colorectal cancer correlates
      with lymphatic dissemination  and reduced CD8+ T-cell infiltration.
AB  - BACKGROUND: Chemokines and their receptors have been proposed to distinctly
      contribute to tumor growth, dissemination, and local immune escape. The aim of
      this study was to evaluate the relevance of the chemokine receptor CCR5
      expression for the progression of human colorectal cancer. METHODS: CCR5
      expression was assessed by RT-PCR analysis in 103 colorectal cancer patients.
      Intensity of CCR5 expression was correlated with both tumor and patient
      characteristics. Infiltration of tumor margins with CD8(+) T cells in the context
      of CCR5 expression was analyzed by immunohistochemistry in additional 18
      colorectal cancer specimens. RESULTS: Human colorectal cancer revealed variable
      intensities of CCR5 expression ranging from absent (48/103: 47%), weak (30/103:
      29%), intermediate (13/103: 13%), to strong (12/103: 12%). Absent or weak CCR5
      expression was significantly associated with advanced UICC stages (P=0.02) and
      lymphatic metastasis (P=0.05). In addition, CCR5 expression positively correlated
      with CD8(+) T-cell infiltration in tumor margins (P=0.001). CONCLUSION: In
      summary, intermediate and strong CCR5 expression was significantly associated
      with nonmetastatic colorectal cancer and increased CD8(+) T-cell infiltration.

PMID- 20054601
TI  - Effect of probiotic bacterial strains of Lactobacillus, Bifidobacterium, and
      Enterococcus on enteroaggregative Escherichia coli.
AB  - The effects of nine probiotic strains of Lactobacillus, Bifidobacterium, and
      Enterococcus on the growth, adhesion activity, and biofilm formation of
      enteroaggregative Escherichia coli (EAggEC) were examined. The culture
      supernatant of the E. faecium strain, with or without pH adjustment to a neutral
      pH, had a strong bactericidal effect on EAggEC, including induction of membrane
      damage and cell lysis. Supernatants of the L. casei ss. casei and L. casei ss.
      rhamnosus strains also had a bactericidal effect on EAggEC, but this activity was
      abolished by pH adjustment to a neutral pH. No inhibitory effect of the culture
      supernatants of Bifidobacterium or E. faecalis strains was detected. Adhesion of
      EAggEC to intestinal epithelial cells was not inhibited by the bacterial strains
      tested. Two strains of L. casei enhanced EAggEC biofilm formation, which was
      characterized by increased bacterial proliferation. These results suggest that
      the three different bacterial species; Lactobacillus, Bifidobacterium, and
      Enterococcus, have different effects on EAggEC, and that further analysis is
      required for the practical use of these bacteria as probiotics against EAggEC
      infection.

PMID- 20054602
TI  - Immune thrombocytopenia associated with pulmonary tuberculosis.
AB  - Many hematological abnormalities, such as pancytopenia, anemia, and leukocytosis,
      can be associated with tuberculosis (TB). Immune thrombocytopenic purpura (ITP)
      is an extremely rare event in TB. We report a 46-year-old male patient who was
      admitted to hospital with a history of weight loss, combined with hemoptysis,
      fever, cough, sputum, general malaise, and night sweats. Physical examination
      revealed a body temperature of 38.8  degrees C, and petechiae distributed over
      the lower extremities. Laboratory findings were as follows: erythrocyte
      sedimentation rate, 84 mm/h; white blood cells, 7070/mm3; hemoglobin, 11.7 g/dl;
      and platelet count, 4000/mm3. On Ziehl-Neelsen stain of sputum, acid-fast bacilli
      were observed. Antituberculosis therapy was started, together with prednisolone,
      0.5 mg/kg per day, from the day of admission. He was treated successfully with
      the steroid and antituberculous drugs.

PMID- 20054603
TI  - Ecthyma gangrenosum caused by Pseudomonas aeruginosa in a patient with
      astrocytoma treated with chemotherapy.
AB  - Ecthyma gangrenosum, presenting as embolic lesions caused by Pseudomonas
      aeruginosa infection, has distinct pathognomonic features and a high mortality
      rate in patients with bacteremia, but when recognized early is easily treated. In
      this case report we describe this disseminated infection in an adult patient
      treated with chemotherapy for an astrocytoma.

PMID- 20054604
TI  - Systemic lupus erythematosus after thymectomy for myasthenia gravis: a case
      report and review of the literature.
AB  - Here, we report a case of systemic lupus erythematosus in a 13-year-old girl who
      developed the disease 3 years after thymectomy performed for the treatment of
      myasthenia gravis. The presenting symptoms were fever, generalized fatigability,
      bilateral loin pain, weight loss, arthralgia, hair loss, and recurrent painless
      mouth ulcers. Laboratory findings revealed proteinuria, hematuria, anemia,
      leucopenia, a high titer of antinuclear antibodies (ANA), anti-dsDNA, and
      decreased complement (C3 and C4) levels. There was minimal ascitis and
      pericardial effusion. Renal biopsy showed lupus nephritis class IV. The diagnosis
      of systemic lupus erythematosus was established based on the clinical and
      laboratory findings. The activity of systemic lupus erythematosus was controlled
      by pulsed treatment with methyl prednisolone followed by long-term oral
      glucocorticoid and immunosuppressive therapy. This study highlights the immune
      system derangement following thymectomy. It also examines the relevant
      literature.

PMID- 20054605
TI  - Mapping vascular response to in vivo hemodynamics: application to increased flow
      at the basilar terminus.
AB  - Hemodynamic forces play critical roles in vascular pathologies such as
      atherosclerosis, aneurysms, and stenosis. However, detailed relationships between
      the specific in vivo hemodynamic microenvironment and vascular responses leading
      to the triggering or exacerbation of pathological remodeling of the vessel remain
      elusive. We have developed a hemodynamics-biology co-mapping technique that
      enables in situ correlation between the in vivo blood flow field and vascular
      changes secondary to hemodynamic insult. The hemodynamics profile is obtained
      from computational fluid dynamics simulation within the vascular geometry
      reconstructed from three-dimensional in vivo images, whereas the vascular
      response is obtained from histology or immunohistochemistry on harvested vascular
      tissue. The hemodynamics field is virtually sectioned in the histological slicing
      planes and digitally co-mapped with the histological images, thereby enabling
      correlation of the specific local vascular responses with the inciting
      hemodynamic stresses. We demonstrate application of this technique to rabbit
      basilar terminus subjected to elevated flow. Morphological changes at the basilar
      terminus 5 days after the flow increase were co-mapped with the initial wall
      shear stress and wall shear stress gradient distributions, from which
      localization of destructive remodeling in a specific hemodynamic zone was
      noticed. This method paves the way for further investigations to determine the
      connection between in vivo mechanical stimuli and biological responses, such as
      initiation of aneurysmal remodeling.

PMID- 20054606
TI  - Presentation of similar images as a reference for distinction between benign and
      malignant masses on mammograms: analysis of initial observer study.
AB  - The effect of the presentation of similar images for distinction between benign
      and malignant masses on mammograms was evaluated in the observer performance
      study. Images of masses were obtained from the Digital Database for Screening
      Mammography. We selected 50 benign and 50 malignant masses by a stratified
      randomization method. For each case, similar images were selected based on the
      size of masses and the similarity measures. Radiologists were shown images with
      unknown masses and asked to provide their confidence level that the lesions were
      malignant before and after the presentation of the similar images. Eleven
      observers, including three attending breast radiologists, three breast imaging
      fellows, and five residents, participated. The average areas under the receiver
      operating characteristic curves without and with the presentation of the similar
      images were almost equivalent. However, there were many cases in which the
      similar images caused beneficial effects to the observers, whereas there were a
      small number of cases in which the similar images had detrimental effects. From a
      detailed analysis of the reasons for these detrimental effects, we found that the
      similar images would not be useful for diagnosis of rare and very difficult
      cases, i.e., benign-looking malignant and malignant-looking benign cases. In
      addition, these cases should not be included in the reference database, because
      radiologists would be confused by these unusual cases. The results of this study
      could be very important and useful for the future development and improvement of
      a computer-aided diagnosis system.

PMID- 20054611
TI  - Genome-wide association studies and the genetics  of entrepreneurship.

PMID- 20054610
TI  - Genome-wide profiling of histone H3 lysine 9 acetylation and dimethylation in
      Arabidopsis reveals correlation between multiple histone marks and gene
      expression.
AB  - Lysine residue 9 of histone H3 can either be acetylated or mono-, di-, or tri
      methylated. These epigenetic states have a diverse impact on regulating gene
      transcriptional activity and chromatin organization. H3K9ac is invariably
      correlated with transcriptional activation, whereas H3K9me2 has been reported to
      be mainly located in constitutive heterochromatin in Arabidopsis. Here, we
      present epigenetic landscapes for histone H3 lysine 9 acetylation (H3K9ac) and
      dimethylation (H3K9me2) in Arabidopsis seedlings. The results show that H3K9ac
      targeted 5,206 non-transposable element (non-TE) genes and 321 transposable
      elements (TEs), whereas H3K9me2 targeted 2,281 TEs and 1,112 non-TE genes. H3K9ac
      was biased towards the 5' end of genes and peaked at the ATG position, while
      H3K9me2 tended to span the entire gene body. H3K9ac correlated with high gene
      expression, while H3K9me2 correlated with low expression. Analyses of H3K9ac and
      H3K9me2 with the available datasets of H3K27me3 and DNA methylation revealed a
      correlation between the occurrence of multiple epigenetic modifications and gene
      expression. Genes with H3K9ac alone were actively transcribed, while genes that
      were also modified by either H3K27me3 or DNA methylation showed a lower
      expression level, suggesting that a combination of repressive marks weakened the
      positive regulatory effect of H3K9ac. Furthermore, we observed a significant
      increase of the H3K9ac modification level of selected target genes in hda19
      (histone deacetylase 19) mutant seedlings, which indicated that HDA19 plays an
      important role in regulating the level of H3K9ac and thereby influencing the
      transcriptional activity in young seedlings.

PMID- 20054607
TI  - T helper 17 cells: discovery, function, and physiological trigger.
AB  - In the few years since their discovery, T helper 17 cells (T(H)17) have been
      shown to play an important role in host defense against infections, and in tissue
      inflammation during autoimmunity. T(H)17 cells produce IL-17, IL-21, IL-10, and
      IL-22 cytokines, and thus have broad effects on a variety of tissues. Notably,
      the requirement for the immunosuppressive cytokine TGF-beta along with the pro
      inflammatory cytokine IL-6 for T(H)17 differentiation supports the intimate
      relationship between the T(H)17 subset and FOXP3(+) regulatory T cells. Here, we
      discuss current knowledge on effector functions and differentiation of the T(H)17
      lineage. Furthermore, we now know of a physiological stimulus for T(H)17
      differentiation: innate immune recognition of cells undergoing apoptosis as a
      direct result of infection induces unique development of this subset. As our
      knowledge of T(H)17 and T regulatory cells grows, we are building on a new
      framework for the understanding of effector T cell differentiation and the
      biology of CD4(+) T cell adaptive immune responses.

PMID- 20054612
TI  - Dealing with emigration in cohort studies: follow-up of mortality  and cancer
      incidence among Norwegians born between 1967  and 1976.
AB  - Emigration causes loss to follow-up. The study aim was to assess the influence of
      the choice of handling migration in population-based cohort studies on estimated
      mortality and cancer incidence in the population of origin. All persons born in
      Norway between 1967 and 1976 and who were not registered dead before 1992 (N =
      614,176) were followed up in national registries regarding migration movements,
      death, and incident cancer between 1992 and 2004. A total of 40,366 (6.6%) of the
      study population had between 1 and 13 migration movements and 5,354 deaths and
      4,447 first cancer cases were recorded during follow-up. Four different follow-up
      scenarios concerning migration were analysed: considering only person-time before
      emigration; considering person-time as national residents both before emigration
      and after repatriation; disregarding whether emigration took place or not; and
      excluding all who emigrated during follow-up. Mortality and cancer incidence
      rates were compared in Poisson regression models. Mortality and cancer incidence
      were only marginally influenced by choice of follow-up scenario. Mortality was
      higher after repatriation, in particular during the first year of follow-up (rate
      ratio 2.03; 95% confidence interval 1.02-4.03). This excess had little influence
      on total population rates. Cancer incidence was not affected by repatriation
      status. Mortality rates after repatriation were probably elevated because persons
      who expected to die shortly were more prone to return to their native country
      ("salmon bias"). The analytical choice concerning follow-up has little influence
      on outcome occurrences in populations with rather low migration rates. However,
      the best solution is apparently to censor out persons at the date of emigration
      in order to avoid salmon bias.

PMID- 20054614
TI  - Predicting human immunodeficiency virus protease cleavage sites in nonlinear
      projection space.
AB  - HIV-1 protease has a broad and complex substrate specificity. The discovery of an
      accurate, robust, and rapid method for predicting the cleavage sites in proteins
      by HIV protease would greatly expedite the search for inhibitors of HIV protease.
      During the last two decades, various methods have been developed to explore the
      specificity of HIV protease cleavage activity. However, because little
      advancement has been made in the understanding of HIV-1 protease cleavage site
      specificity, not much progress has been reported in either extracting effective
      methods or maintaining high prediction accuracy. In this article, a theoretical
      framework is developed, based on the kernel method for dimensionality reduction
      and prediction for HIV-1 protease cleavage site specificity. A nonlinear
      dimensionality reduction kernel method, based on manifold learning, is proposed
      to reduce the high dimensions of protease specificity. A support vector machine
      is applied to predict the protease cleavage. Superior performance in comparison
      to that previously published in literature is obtained using numerical
      simulations showing that the basic specificities of the HIV-1 protease are
      maintained in reduction feature space, and by combining the nonlinear
      dimensionality reduction algorithm with a support vector machine classifier.

PMID- 20054613
TI  - Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of
      PI3-K, mTOR, GSK-3beta, and apoptosis.
AB  - Post-conditioning by repetitive cycles of reperfusion/ischemia after prolonged
      ischemia protects the heart from infarction. The objectives of this study were:
      Are kinases (PI3-kinase, mTOR, and GSK-3beta) involved in the signaling pathway
      of post-conditioning? Does post-conditioning result in a diminished necrosis or
      apoptosis? In open chest rats the infarct size was determined after 30 min of
      regional ischemia and 30 min of reperfusion using propidium iodide and
      microspheres. Post-conditioning was performed by three cycles of 30 s reperfusion
      and reocclusion each, immediately upon reperfusion. PI3-kinase and mTOR were
      blocked using wortmannin (0.6 mg/kg) or rapamycin (0.25 mg/kg), respectively. The
      phosphorylation of GSK-3beta and p70S6K was determined with phospho-specific
      antibodies. TUNEL staining and detection of apoptosis-inducing factor (AIF) were
      used for the determination of apoptosis. Control hearts had an infarct size of 49
      +/- 3%, while post-conditioning significantly reduced it to 29 +/- 3% (P < 0.01).
      Wortmannin as well as rapamycin completely blocked the infarct size reduction of
      post-conditioning (51 +/- 2% and 54 +/- 5%, respectively). Western blot analysis
      revealed that post-conditioning increased the phosphorylation of GSK-3beta by 2.3
      times (P < 0.01), and this increase could be blocked by wortmannin, a PI3-kinase
      inhibitor. Although rapamycin blocked the infarct size reduction, phosphorylation
      of p70S6K was not increased in post-conditioned hearts. After 2 h of reperfusion,
      the post-conditioned hearts had significantly fewer TUNEL-positive nuclei (35 %)
      compared to control hearts (53%; P < 0.001). AIF was equally reduced in post
      conditioned rat hearts (P < 0.05 vs. control). Infarct size reduction by ischemic
      post-conditioning of the in vivo rat heart is PI3-kinase dependent and involves
      mTOR. Furthermore, GSK-3beta, which is thought to be a regulator of the mPTP, is
      part of the signaling pathway of post-conditioning. Finally, apoptosis was
      inhibited by post-conditioning, which was shown by two independent methods. The
      role of apoptosis and/or autophagy in post-conditioning has to be further
      elucidated to find therapeutic targets to protect the heart from the consequences
      of acute myocardial infarction.

PMID- 20054615
TI  - Early predictors of cardiac decompensation in experimental volume overload.
AB  - In humans, volume overload (VOL) increases the risk of sudden cardiac death, but
      there is also important inter-individual variability, presumably because of
      differences in genetic backgrounds. Although VOL has rapid effects on myocardial
      properties, it is not known to which extent the severity of these early responses
      correlate with the effect of sustained VOL on mortality. In order to test this
      question, we induced VOL in male rats from two genetically distinct strains
      [i.e., Sprague-Dawley (SD) and Wistar Kyoto-derived Hyperactive (WKHA) rats] by
      creating a surgical aorto-caval fistula (ACF). Only 36% of SD rats remained alive
      after 39 weeks of ACF, in contrast to 82% of the operated WKHA rats. We also
      monitored myocardial hemodynamic function, mitochondrial properties, left
      ventricular (LV) morphology and LV wall diastolic properties at different times
      ranging from 2 to 12 weeks after either ACF or sham surgery. ACF had a rapid
      impact on the LV walls of both rat strains, but the only variables that were
      affected to a greater extent in the mortality-prone SD strain were normalized LV
      weight, LV cavity area, and myocardial wall stiffness. In contrast, there were
      only marginal strain-related differences in the way ACF affected hemodynamic and
      mitochondrial functions. Thus, while early morphologic responses of LV walls to
      ACF (along with their downstream consequences on myocardial diastolic wall
      stress) correlated well with strain-dependent differences in late mortality,
      other functional changes showed no predictive effects. Close monitoring of early
      changes in cardiac geometry (as well as new methods to analyze myocardial
      diastolic strain) might, therefore, be helpful to further improve risk
      stratification in humans with volume overload cardiopathies.

PMID- 20054616
TI  - Sprouty1 inhibits angiogenesis in association with up-regulation of p21 and p27.
AB  - Sprouty1 (Spry1) is a conserved antagonist of FGF signaling. The goal of this
      study was to further explore the downstream mechanisms governing Spry1 inhibition
      of endothelial cell proliferation. Up-regulation of Spry1 in HUVECs inhibited
      tube formation on Matrigel (n = 6, P < 0.001). This was associated with decreased
      proliferation as measured by BrdU incorporation (n = 6, P < 0.001) and increased
      protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A), p21 and
      cyclin-dependent kinase inhibitor 1B (CDKN1B), p27. A transcriptional analysis
      using a targeted human angiogenesis array following up-regulation of Spry1
      demonstrated a >2-fold increase in an anti-angiogenic factor, serpin peptidase
      inhibitor, clad F (Serpinf1), and a >2-fold decrease in pro-angiogenic factors
      fms-related tyrosine kinase 1 (FLT1), angiopoietin2 (Ang-2), and placental growth
      factor (PGF) (n = 2). To define upstream mechanisms that may regulate endogenous
      Spry1, we performed a search for responsive elements upstream of the promoter
      region. This search resulted in the identification of multiple degenerate hypoxia
      responsive elements. Exposure to hypoxia resulted in a significant increase in
      Spry1 expression (n = 8, P < 0.01). These findings shed new light on downstream
      signaling pathways associated with Spry1 anti-proliferative responses, and
      provide new evidence that hypoxia stimulates Spry1 expression.

PMID- 20054618
TI  - New SPME guidelines.

PMID- 20054617
TI  - Fretting wear behavior of calcium phosphate-mullite composites in dry and albumin
      containing simulated body fluid conditions.
AB  - In a recent work, it has been shown that it is possible to achieve a better
      combination of compressive strength, flexural strength and toughness properties
      in calcium phosphate (CaP) composites containing 20 and 30 wt% mullite
      (3Al(2)O(3).2SiO(2)). In view of their potential application as load bearing
      implants, the present work reports the friction and wear properties of the newly
      developed composites against zirconia under dry ambient as well as in simulated
      body fluid (SBF) containing bovine serum albumin (BSA) protein. For comparison,
      experiments were also conducted on monolithic hydroxyapatite (HAp,
      Ca(10)(PO(4))(6)(OH)(2)) and mullite under identical conditions. Under the
      investigated fretting conditions, the mullite-containing composites exhibited
      higher coefficient of friction (COF) of 0.4-0.6, compared to pure HAp (COF
      approximately 0.25-0.3). Although the wear resistance of the composites
      containing 20 or 30 wt% mullite was better in dry conditions, higher wear rate
      was measured in SBF conditions. The difference in tribological properties has
      been analyzed in reference to the difference in phase assemblage and mechanical
      properties. A comparison with some competing biomaterials reveals good potential
      of the investigated CaP-mullite composites for application as wear resistant
      implants.

PMID- 20054619
TI  - Impacts of elevated atmospheric CO2 and O3 on forests: phytochemistry, trophic
      interactions, and ecosystem dynamics.
AB  - Prominent among the many factors now affecting the sustainability of forest
      ecosystems are anthropogenically-generated carbon dioxide (CO2) and ozone (O3).
      CO2 is the substrate for photosynthesis and thus can accelerate tree growth,
      whereas O3 is a highly reactive oxygen species and interferes with basic
      physiological functions. This review summarizes the impacts of CO2 and O3 on tree
      chemical composition and highlights the consequences thereof for trophic
      interactions and ecosystem dynamics. CO2 and O3 influence phytochemical
      composition by altering substrate availability and biochemical/physiological
      processes such as photosynthesis and defense signaling pathways. Growth of trees
      under enriched CO2 generally leads to an increase in the C/N ratio, due to a
      decline in foliar nitrogen and concomitant increases in carbohydrates and
      phenolics. Terpenoid levels generally are not affected by atmospheric CO2
      concentration. O3 triggers up-regulation of antioxidant defense pathways, leading
      to the production of simple phenolics and flavonoids (more so in angiosperms than
      gymnosperms). Tannins levels generally are unaffected, while terpenoids exhibit
      variable responses. In combination, CO2 and O3 exert both additive and
      interactive effects on tree chemical composition. CO2-and O3-mediated changes in
      plant chemistry influence host selection, individual performance (development,
      growth, reproduction), and population densities of herbivores (primarily
      phytophagous insects) and soil invertebrates. These changes can effect shifts in
      the amount and temporal pattern of forest canopy damage and organic substrate
      deposition. Decomposition rates of leaf litter produced under elevated CO2 and O3
      may or may not be altered, and can respond to both the independent and
      interactive effects of the pollutants. Overall, however, CO2 and O3 effects on
      decomposition will be influenced more by their impacts on the quantity, rather
      than quality, of litter produced. A prominent theme to emerge from this and
      related reviews is that the effects of elevated CO2 and O3 on plant chemistry and
      ecological interactions are highly context- and species-specific, thus
      frustrating attempts to identify general, global patterns. Many of the
      interactions that govern above- and below-ground community and ecosystem
      processes are chemically mediated, ultimately influencing terrestrial carbon
      sequestration and feeding back to influence atmospheric composition. Thus, the
      discipline of chemical ecology is fundamentally important for elucidating the
      impacts of humans on the health and sustainability of forest ecosystems. Future
      research should seek to increase the diversity of natural products, species, and
      biomes studied; incorporate long-term, multi-factor experiments; and employ a
      comprehensive "genes to ecosystems" perspective that couples genetic/genomic
      tools with the approaches of evolutionary and ecosystem ecology.

PMID- 20054620
TI  - Non-volatile intact indole glucosinolates are host recognition cues for
      ovipositing Plutella xylostella.
AB  - The diamondback moth (Plutella xylostella), a crucifer-specialist pest, has been
      documented to employ glucosinolates as host recognition cues for oviposition.
      Through the use of mutant Arabidopsis thaliana plants, we investigated the role
      of specific classes of glucosinolates in the signaling of oviposition by P.
      xylostella in vivo. Indole glucosinolate production in A. thaliana was found to
      be crucial in attracting oviposition. Additionally, indole glucosinolates
      functioned as oviposition cues only when in their intact form. 4-Methoxy-indol-3
      ylmethylglucosinolate was implicated as an especially strong oviposition
      attractant in vitro, suggesting that indole glucosinolate secondary structure may
      play a role in P. xylostella host recognition as well. Aliphatic glucosinolate
      derived breakdown products were found to attract P. xylostella, but only after
      damage or in the absence of indole glucosinolates. Furthermore, mutant plants
      lacking both intact indole glucosinolates and aliphatic glucosinolate breakdown
      products exhibited decreased oviposition attractiveness beyond that of the
      progenitor mutants lacking either component of the glucosinolate-myrosinase
      system. Therefore, we conclude that nonvolatile indole glucosinolates and
      volatile aliphatic glucosinolate breakdown products both appear to play important
      roles as host recognition cues for P. xylostella oviposition.

PMID- 20054621
TI  - Social and psychological challenges of poker.
AB  - Poker is a competitive, social game of skill and luck, which presents players
      with numerous challenging strategic and interpersonal decisions. The adaptation
      of poker into a game played over the internet provides the unprecedented
      opportunity to quantitatively analyze extremely large numbers of hands and
      players. This paper analyzes roughly twenty-seven million hands played online in
      small-stakes, medium-stakes and high-stakes games. Using PokerTracker software,
      statistics are generated to (a) gauge the types of strategies utilized by players
      (i.e. the 'strategic demography') at each level and (b) examine the various
      payoffs associated with different strategies at varying levels of play. The
      results show that competitive edges attenuate as one moves up levels, and tight
      aggressive strategies--which tend to be the most remunerative--become more
      prevalent. Further, payoffs for different combinations of cards, varies between
      levels, showing how strategic payoffs are derived from competitive interactions.
      Smaller-stakes players also have more difficulty appropriately weighting
      incentive structures with frequent small gains and occasional large losses.
      Consequently, the relationship between winning a large proportion of hands and
      profitability is negative, and is strongest in small-stakes games. These
      variations reveal a meta-game of rationality and psychology which underlies the
      card game. Adopting risk-neutrality to maximize expected value, aggression and
      appropriate mental accounting, are cognitive burdens on players, and underpin the
      rationality work--reconfiguring of personal preferences and goals--players engage
      into be competitive, and maximize their winning and profit chances.

PMID- 20054622
TI  - Prevalence of adolescent problem gambling, related harms and help-seeking
      behaviours among an Australian population.
AB  - Epidemiological studies have consistently reported prevalence rates ranging
      between 0.9 and 23.5% for problem gambling among young people. With such a large
      range reported in the literature, it is clear that more research in this area
      would be of value. The current study investigated the prevalence rate of
      adolescent gambling and problem gambling and explored types of harm-related and
      help-seeking behaviours associated with gambling specific to this population in
      an Australian setting. A self-administered battery of questionnaires was
      distributed to 252 students aged 12-18 years, attending four private schools in
      the Eastern suburbs of Sydney, Australia. The battery included a self
      administered socio-gambling demographic questionnaire, the Diagnostic and
      Statistical Manual Fourth Edition Multiple Response Juvenile (DSM-IV-MR-J)
      diagnostic instrument to assess problem gambling status, the Gambling Attitudes
      Scale, and questionnaires using a Likert scale to measure gambling-related harms
      and help-seeking behaviours. The prevalence rate among this group was found to be
      6.7%. The study found further support for previous findings suggesting that a
      significant proportion of young people meet criteria for problem gambling, that
      males are at-risk and that few adolescents are able to recognise when gambling is
      problematic or access mental health professionals for assistance.

PMID- 20054623
TI  - Views of discrimination among individuals confronting genetic disease.
AB  - Though the US passed the Genetic Information Non-Discrimination Act, many
      questions remain of how individuals confronting genetic disease view and
      experience possible discrimination. We interviewed, for 2 hours each, 64
      individuals who had, or were at risk for, Huntington's Disease, breast cancer, or
      Alpha-1 antitrypsin deficiency. Discrimination can be implicit, indirect and
      subtle, rather than explicit, direct and overt; and be hard to prove. Patients
      may be treated "differently" and unfairly, raising questions of how to define
      "discrimination", and "appropriate accommodation". Patients were often unclear
      and wary about legislation. Fears and experiences of discrimination can shape
      testing, treatment, and disclosure. Discrimination can be subjective, and take
      various forms. Searches for only objective evidence of it may be inherently
      difficult. Providers need to be aware of, and prepared to address, subtle and
      indirect discrimination; ambiguities, confusion and potential limitations
      concerning current legislation; and needs for education about these laws.
      Policies are needed to prevent discrimination in life, long-term care, and
      disability insurance, not covered by GINA.

PMID- 20054624
TI  - Dipyridamole increases gap junction coupling in bovine GM-7373 aortic endothelial
      cells by a cAMP-protein kinase A dependent pathway.
AB  - The scrape-loading/dye transfer technique was applied on the bovine aortic
      endothelial cell line GM-7373 to analyze the effects of the antithrombolytic drug
      dipyridamole on gap junction coupling in endothelial cells. We found that a cell
      treatment for 24 h with dipyridamole in therapeutically relevant concentrations
      (1-100 microM) increased gap junction coupling in a dose dependent manner.
      Similar to dipyridamole, forskolin as well as 8-Br-cAMP increased the gap
      junction coupling, while dibutyryl-cGMP (db-cGMP) did not affect the gap junction
      coupling of the GM-7373 endothelial cells. In parallel, a pharmacological
      inhibition of protein kinase A (PKA) with N-[2-(p-bromocinnamylamino)ethyl]-5
      isoquinolinesulfonamide dihydrochloride (H-89), antagonised the action of
      dipyridamole on gap junction coupling. We propose that the observed dipyridamole
      induced increase in gap junction coupling in endothelial cells is related to a
      cAMP-PKA dependent phosphorylation pathway. The report shows that gap junction
      coupling in endothelial cells is a suitable therapeutic target for treatment of
      cardiovascular diseases.

PMID- 20054625
TI  - Study on the effects of chloride depletion on photosystem II using different
      chloride depletion methods.
AB  - Chloride is an indispensable factor for the functioning of oxygen evolving
      complex (OEC) and has protective and activating effects on photosystem II. In
      this study we have investigated mainly by EPR, the properties of chloride
      sufficient, chloride-deficient and chloride-depleted thylakoid membranes and
      photosystem II enriched membranes from spinach. The results on the effects of
      different chloride depletion methods on the structural and functional aspects of
      photosystem II showed that chloride-depletion by treating PS II membranes with
      high pH is a relatively harsh way causing a significant and irreparable damage to
      the PS II donor side. Damage to the acceptor side of PS II was recovered almost
      fully in chloride-deficient as well as chloride-depleted PS II membranes.

PMID- 20054626
TI  - Independent and interactive associations of prenatal mood and substance use with
      infant birth outcomes.
AB  - The main objective of this work is to examine low prenatal mood, alcohol and
      tobacco use and rates of preterm (PTB) and low birth weight (LBW) births among
      women in Minnesota between 2002 and 2006. We examined the Minnesota version of
      the national, cross-sectional survey of postpartum women, the Pregnancy Risk
      Assessment Monitoring System (MN PRAMS). Of the 11,891 women sampled in 2002
      2006, 7,457 had complete data for analysis; the weighted response rates averaged
      76%. The major variables of interest were: LBW, PTB, maternal mood during
      pregnancy, prenatal alcohol use, prenatal tobacco use and interaction terms
      created from the mood and substance use variables. Women with low mood who used
      tobacco during pregnancy were twice as likely to have a LBW infant as women who
      did not smoke and reported high mood (AOR = 2.12, 95% CI: 1.35, 3.33, P = 0.001).
      Among women who abstained from alcohol during pregnancy, those with low mood were
      at an increased risk for PTB (AOR = 1.95, 95% CI: 1.54-2.45, P < 0.0001) compared
      to women with high mood. Low maternal mood was associated with increased risks
      for PTB, and LBW births among MN PRAMS respondents. Substance use and low
      prenatal mood co-occur and the combined effect on PTB and LBW birth outcomes
      warrants further investigation.

PMID- 20054627
TI  - Reducing low birth weight infancy: assessing the effectiveness of the Health
      Start program in Arizona.
AB  - This study compares the incidence of low birth weight among mothers enrolled in
      Arizona's Health Start program to a sample of non-Health Start mothers with
      similar medical and social risk factors. A quasi-experimental design was used to
      match Health Start program participants to non-participants on the basis of
      similar medical and social risk factors. Health Start program data were linked to
      birth certificate data to create a sample of 5,480 pregnant women. A logistic
      regression analysis was conducted to predict the likelihood of having a normal
      birth weight (i.e., 2,500 g or more). The findings indicate that Health Start
      mothers had twice as better odds of having a normal birth weight than non-Health
      Start mothers, even after controlling for gestational age, adequacy of prenatal
      care, mother's history of preterm birth, weight gain during pregnancy, alcohol
      and cigarette use, mother's age, education and residency. Hispanic women in the
      program were three times as likely to have a normal birth weight baby when
      compared to Hispanics who were not in the program and twice as likely as non
      participant Whites. And lastly, women in urban settings had better birth
      outcomes, especially Hispanic women. Evidence suggests that newborn infants of
      mothers enrolled in the Health Start Program had better birth weight outcomes
      even after controlling for the effects of possible confounders. However, the
      program seems to affect Hispanics and non-Hispanic Whites differently; in
      particular, Hispanics who are in the program demonstrated the best birth
      outcomes. One possible explanation for the general success of the program could
      be that program participants reported lower cigarette use during pregnancy. A
      limitation of this study is that that there could be reporting bias on the part
      of Health Start participants about their risks to enter into the program, which
      is difficult to verify.

PMID- 20054628
TI  - Social Story interventions for students with autism spectrum disorders: a meta
      analysis.
AB  - A meta-analysis of single-subject research was conducted, examining the use of
      Social Stories and the role of a comprehensive set of moderator variables
      (intervention and participant characteristics) on intervention outcomes. While
      Social Stories had low to questionable overall effectiveness, they were more
      effective when addressing inappropriate behaviors than when teaching social
      skills. Social Stories also seemed to be associated with improved outcomes when
      used in general education settings and with target children as their own
      intervention agents. The role of other variables of interest, such as
      participants' age, diagnosis, and skill development, the format of Social
      Stories, the length of the intervention, and the use of assessment (e.g.,
      comprehension checks) also was explored.

PMID- 20054629
TI  - Right hemisphere dysfunction and metaphor comprehension in young adults with
      Asperger syndrome.
AB  - This study examined whether the known difficulties in metaphor comprehension
      exhibited by persons with Asperger syndrome (AS) can be explained by a
      dysfunctional right hemisphere (RH). Using the divided visual field paradigm, 27
      AS participants and 36 matched controls were presented with word pairs of four
      types (literal, conventional metaphors, novel metaphors, and unrelated word
      pairs), and were asked to perform a semantic judgment task. The main hypothesis
      was that whereas the control group participants will show RH superiority for
      novel metaphor processing, no RH superiority will be found in the AS group.
      Results indeed indicate much less RH contribution to novel metaphor comprehension
      in AS, and are discussed in light of linguistic models and the neurobiology of
      autism.

PMID- 20054630
TI  - Using the childhood autism rating scale to diagnose autism spectrum disorders.
AB  - This study investigated the childhood autism rating scale (CARS) as a tool for
      ASD diagnoses for 2-year-old (n = 376) and 4-year-old (n = 230) children referred
      for possible autism. The cut-off score to distinguish autistic disorder from PDD
      NOS was 32 in the 2-year-old sample (consistent with Lord in J Child Psychol
      Psychiatry Allied Discipl, 36, 1365-1382, 1995), and 30 in the 4-year-old sample,
      with good sensitivity and specificity at both ages. The cut-off score to
      distinguish ASD from non-ASD at both ages was 25.5, with good sensitivity and
      specificity. Results confirm the utility of the CARS in distinguishing autistic
      disorder from PDD-NOS, and distinguishing ASD from other developmental disorders
      and typical development and suggest that an ASD cutoff around 25, which is in
      common clinical use, is valid.

PMID- 20054631
TI  - Gender constructions of male sex offenders in Germany: narrative analysis from
      group psychotherapy.
AB  - This study was conducted to analyze how male sexual offenders construct mental
      images of masculinity and femininity to provide insight into therapeutic
      treatment for such patients. Thematerial examined in this studywas comprised of
      21 videotaped prison group therapy sessions in which the participating sexual
      offenders talked about their crimes and biographies. Aqualitative data analysis
      softwarewas usedto apply a modified grounded theorymethodology to the transcribed
      sessions. The resulting categories can be understood as descriptions of how the
      imprisoned men constructed gender images, and were based on three narrative
      levels: the structure of narration, the narrative positions in the story, and the
      interaction between the narrator and the other participants. According to the
      categories describedin the narrative positions (the narrated self and the
      narrated significant male others), we constructed masculinity categorizations
      which corresponded to specific images of femininity (derived from the narrated
      significant female others).The constructionsprovided insight into the selfimage
      of the narrator, as well as the accountability and positioning of himself and the
      other in regard to perpetrator-victim constructions. The study further revealed
      whether the participants either accepted or rejected responsibility and guilt for
      their crimes; this is essential for psychotherapeutic process and treatment.

PMID- 20054632
TI  - Cafe discussions on oral sex, oral cancer, and HPV infection: summative report.
AB  - Recent emphasis has been placed on the potential links between oral sex, HPV
      infection, and oral cancer development. Such links were addressed by researchers,
      clinicians, and the community during two Cafe Scientifique discussions in October
      and November 2008, in Vancouver, Canada. The Cafes gathered panels of experts on
      oral pathology, dentistry, oncology, social work, and community-based research
      who interacted with an audience of policy makers, health care administrators,
      sociologists, sexologists, pharmacists, clinical and social researchers, social
      workers, technicians, and graduate, undergraduate, and high school students. This
      commentary summarizes the main points discussed during these two events to
      encourage a worldwide open dialogue about potential risks for oral cancer beyond
      tobacco smoking and excessive alcohol consumption as such malignancies have high
      mortality and morbidity, but are yet preventable diseases.

PMID- 20054633
TI  - Socioeconomic position and HIV risk-relevant behavior among lower-income
      heterosexuals in San Francisco.
AB  - We assess whether there is evidence of an association between socioeconomic
      position (SEP) and HIV risk-relevant behavior among lower income heterosexual men
      and women in San Francisco. Respondents residing in low income areas with high
      heterosexual AIDS case burden in San Francisco were recruited through long-chain
      referral in 2006-2007. Risk measures included unprotected vaginal intercourse,
      concurrency and exchange sex. SEP was defined as household annual income, per
      capita income, and employment. Analyses utilized mixed and fixed effects models.
      A total of 164 men and 286 women were included in the study. SEP was only
      significant in the case of exchange sex among men: men reporting annual income
      greater than $30,000 had significantly lower odds of exchange sex relative to
      other men. Evaluating the connection between economic status and HIV requires
      additional studies covering diverse populations. Future studies should focus on
      community economic context as well as individual SEP.

PMID- 20054634
TI  - Designing a mobile phone-based intervention to promote adherence to
      antiretroviral therapy in South India.
AB  - Integration of mobile phone technology into HIV care holds potential,
      particularly in resource-constrained settings. Clinic attendees in urban and
      rural South India were surveyed to ascertain usage of mobile phones and
      perceptions of their use as an adherence aid. Mobile phone ownership was high at
      73%; 26% reported shared ownership. A high proportion (66%) reported using phones
      to call their healthcare provider. There was interest in weekly telephonic
      automated voice reminders to facilitate adherence. Loss of privacy was not
      considered a deterrent. The study presents important considerations in the design
      of a mobile phone-based adherence intervention in India.

PMID- 20054636
TI  - Lack of association of CYP1A2-164 A/C polymorphism with breast cancer
      susceptibility: a meta-analysis involving 17,600 subjects.
AB  - Published data on the association between cytochrome P-450 1A2 (CYP1A2)-164 A/C
      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 CYP1A2-164 A/C polymorphism and breast
      cancer risk. The pooled ORs were performed for co-dominant model (AC versus AA,
      CC versus AA), dominant model (CC + AC versus AA), and recessive model (CC versus
      AA + AC), respectively. A total of 9 studies including 7,580 cases and 10,020
      controls were involved in this meta-analysis. Overall, no significantly elevated
      breast cancer risk was found in all genetic models when all studies were pooled
      into the meta-analysis (AC versus AA: OR = 1.02, 95% CI = 0.92-1.13; CC versus
      AA: OR = 1.17, 95% CI = 0.83-1.64; dominant model: OR = 1.07, 95% CI = 0.93-1.23;
      and recessive model: OR = 1.13, 95% CI = 0.82-1.55). In the subgroup analysis by
      ethnicity or source of controls, there was still no significant association
      detected in all genetic models. In conclusion, upto date, there is still not
      enough evidence to indicate the association of CYP1A2-164 A/C polymorphism and
      breast cancer development.

PMID- 20054635
TI  - Protective effect of Nigella sativa extract and thymoquinone on serum/glucose
      deprivation-induced PC12 cells death.
AB  - The serum/glucose deprivation (SGD)-induced cell death in cultured PC12 cells
      represents a useful in vitro model for the study of brain ischemia and
      neurodegenerative disorders. Nigella sativa L. (family Ranunculaceae) and its
      active component thymoquinone (TQ) has been known as a source of antioxidants. In
      the present study, the protective effects of N. sativa and TQ on cell viability
      and reactive oxygen species (ROS) production in cultured PC12 cells were
      investigated under SGD conditions. PC12 cells were cultured in DMEM medium
      containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100
      microg/ml streptomycin. Cells were seeded overnight and then deprived of
      serum/glucose for 6 and 18 h. Cells were pretreated with different concentrations
      of N. sativa extract (15.62-250 microg/ml) and TQ (1.17-150 microM) for 2 h. Cell
      viability was quantitated by MTT assay. Intracellular ROS production was measured
      by flow cytometry using 2',7'-dichlorofluorescin diacetate (DCF-DA) as a probe.
      SGD induced significant cells toxicity after 6, 18, or 24 h (P < 0.001).
      Pretreatment with N. sativa (15.62-250 microg/ml) and TQ (1.17-37.5 microM)
      reduced SGD-induced cytotoxicity in PC12 cells after 6 and 18 h. A significant
      increase in intracellular ROS production was seen following SGD (P < 0.001). N.
      sativa (250 microg/ml, P < 0.01) and TQ (2.34, 4.68, 9.37 microM, P < 0.01)
      pretreatment reversed the increased ROS production following ischemic insult. The
      experimental results suggest that N. sativa extract and TQ protects the PC12
      cells against SGD-induced cytotoxicity via antioxidant mechanisms. Our findings
      might raise the possibility of potential therapeutic application of N. sativa
      extract and TQ for managing cerebral ischemic and neurodegenerative disorders.

PMID- 20054637
TI  - Temporal trends in area socioeconomic disparities in breast-cancer incidence and
      mortality, 1988-2005.
AB  - Since an overarching goal of Healthy People 2010 was to eliminate health
      disparities, we determined temporal trends in socioeconomic disparities in five
      breast-cancer indicators (in situ, stage I, lymph-node positive, and locally
      advanced breast-cancer incidence, and breast-cancer mortality) by county
      socioeconomic deprivation using 1988-2005 population-based breast-cancer data.
      Using 1988-2005 data from women aged 40 and older from 200 counties in the
      Surveillance, Epidemiology, and End Results program, we examined trends in
      temporal disparities in the five breast-cancer indicators across quartiles of
      county socioeconomic deprivation. County-level trends were summarized using the
      estimated annual percentage change. Observed county rates were smoothed using
      Bayesian hierarchical spatiotemporal methods to calculate measures of absolute
      and relative disparity (using absolute and relative concentration indices) and
      their changes over time. Large increases in in situ breast cancer rates since
      1988 were observed for each of the deprivation quartiles. Absolute and relative
      disparity both increased over time, suggesting increasing disparities across
      levels of county deprivation. Absolute and relative concentration indices were
      near zero for the other four breast-cancer indicators, suggesting no disparities
      among the four quartiles of county deprivation during 1988-2005. Efforts to
      target counties aimed at increasing breast-cancer screening based on their level
      of deprivation will not likely be beneficial.

PMID- 20054638
TI  - Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk:
      a meta-analysis.
AB  - Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of
      exogenous and endogenous substrates. The metabolism of polycyclic aromatic
      hydrocarbons and other procarcinogens through CYP1B1 may well lead to their
      activation. Apart from the extensively studied Val432Leu polymorphism, three
      single nucleotide polymorphisms in CYP1B1 have been studied concerning their
      potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and
      Asn453Ser. This meta-analysis aims to examine whether the three aforementioned
      polymorphisms are associated with breast cancer risk. Eligible articles were
      identified by a search of MEDLINE bibliographical database for the period up to
      December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321
      cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases
      and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases
      and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form
      fixed-effects or random-effects models. Sensitivity analysis excluding studies
      whose genotype frequencies in controls significantly deviated from Hardy-Weinberg
      equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were
      0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly
      subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896-1.097) for
      heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to
      Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984
      (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis
      suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not
      associated with breast cancer risk. Studies on Chinese populations are needed, to
      elucidate race-specific effects on East Asian populations, if any.

PMID- 20054639
TI  - Lack of association between the hOGG1 Ser326Cys polymorphism and breast cancer
      risk: evidence from 11 case-control studies.
AB  - The functional Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase
      (hOGG1) gene has been implicated in breast cancer risk. However, the published
      findings are inconsistent. We therefore performed a meta-analysis to investigate
      this relationship. Eleven published case-control studies, including 6,804 breast
      cancer cases and 6,725 controls were identified. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were used to assess the strength of the association.
      Overall, no significant associations between the hOGG1 Ser326Cys polymorphism and
      breast cancer risk were found for Cys/Cys versus Ser/Ser (OR = 1.07, 95% CI: 0.94
      1.20), Ser/Cys versus Ser/Ser (OR = 0.99, 95% CI: 0.91-1.07), Cys/Cys + Ser/Cys
      versus Ser/Ser (OR = 1.00, 95% CI = 0.93-1.08), and Cys/Cys versus Ser/Cys +
      Ser/Ser (OR = 1.07, 95% CI: 0.97-1.18). In the stratified analysis by ethnicity,
      source of controls, and menopausal status, significant associations were still
      not observed in all genetic models. Taken together, the results suggest that the
      hOGG1 Ser326Cys polymorphism is not associated with breast cancer risk.

PMID- 20054640
TI  - Concordance of HER2 in primary tumor and leptomeningeal metastases: now what?

PMID- 20054641
TI  - The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant
      breast cancer cells.
AB  - Resistance to endocrine therapy agents has presented a clinical obstacle in the
      treatment of hormone-dependent breast cancer. Our laboratory has initiated a
      study of microRNA regulation of signaling pathways that may result in breast
      cancer progression on aromatase inhibitors (AI). Microarray analysis of hormone
      refractory cell lines identified 115 differentially regulated microRNAs, of which
      49 microRNAs were believed to be hormone-responsive. A group of microRNAs were
      inversely expressed in the AI-resistant lines versus LTEDaro and tamoxifen
      resistant. We focused our work on hsa-miR-128a which was hormone-responsive and
      selectively up-regulated in the letrozole-resistant cell lines. Human miR-128a
      was predicted to target the TGFbeta signaling pathway and indeed sensitivity to
      TGFbeta was compromised in the letrozole-resistant cells, as compared to parental
      MCF-7aro. Human miR-128a was shown to negatively target TGFbetaRI protein
      expression by binding to the 3'UTR region of the gene. Inhibition of endogenous
      miR-128a resulted in resensitization of the letrozole-resistant lines to TGFbeta
      growth inhibitory effects. These data suggest that the hormone-responsive miR
      128a can modulate TGFbeta signaling and survival of the letrozole-resistant cell
      lines. To our knowledge, this is the first study to address the role of microRNA
      regulation as well as TGFbeta signaling in AI-resistant breast cancer cell lines.
      We believe that in addition to estrogen-modulation of gene expression, hormone
      regulated microRNAs may provide an additional level of post-transcriptional
      regulation of signaling pathways critically involved in breast cancer progression
      and AI-resistance.

PMID- 20054642
TI  - Synergistic activity of letrozole and sorafenib on breast cancer cells.
AB  - Estrogens induce breast tumor cell proliferation by directly regulating gene
      expression via the estrogen receptor (ER) transcriptional activity and by
      affecting growth factor signaling pathways such as mitogen-activated protein
      kinase (MAPK) and AKT/mammalian target of rapamycin Complex1 (mTORC1) cascades.
      In this study we demonstrated the preclinical therapeutic efficacy of combining
      the aromatase inhibitor letrozole with the multi-kinase inhibitor sorafenib in
      aromatase-expressing breast cancer cell lines. Treatment with letrozole reduced
      testosterone-driven cell proliferation, by inhibiting the synthesis of estrogens.
      Sorafenib inhibited cell proliferation in a concentration-dependent manner; this
      effect was not dependent on sorafenib-mediated inhibition of Raf1, but involved
      the down-regulation of mTORC1 and its targets p70S6K and 4E-binding protein 1 (4E
      BP1). At concentrations of 5-10 MUM the growth-inhibitory effect of sorafenib was
      associated with the induction of apoptosis, as indicated by release of cytochrome
      c and Apoptosis-Inducing Factor into the cytosol, activation of caspase-9 and
      caspase-7, and PARP-1 cleavage. Combination of letrozole and sorafenib produced a
      synergistic inhibition of cell proliferation associated with an enhanced
      accumulation of cells in the G(0)/G(1) phase of the cell cycle and with a down
      regulation of the cell cycle regulatory proteins c-myc, cyclin D1, and phospho
      Rb. In addition, longer experiments (12 weeks) demonstrated that sorafenib may be
      effective in preventing the acquisition of resistance towards letrozole.
      Together, these results indicate that combination of letrozole and sorafenib
      might constitute a promising approach to the treatment of hormone-dependent
      breast cancer.

PMID- 20054644
TI  - Variants in DNA double-strand break repair genes and risk of familial breast
      cancer in a South American population.
AB  - The double-strand break (DSB) DNA repair pathway has been implicated in breast
      cancer (BC). RAD51 and its paralogs XRCC3 and RAD51D play an important role in
      the repair of DSB through homologous recombination (HR). Some polymorphisms
      including XRCC3-Thr241Met, RAD51-135G>C, and RAD51D-E233G have been found to
      confer increased BC susceptibility. In order to detect novel mutations that may
      contribute to BC susceptibility, 150 patients belonging to 150 Chilean BRCA1/2
      negative families were screened for mutations in XRCC3. No mutations were
      detected in the XRCC3 gene. In addition, using a case-control design we studied
      the XRCC3-Thr241Met, and RAD51D-E233G polymorphisms in 267 BC cases and 500
      controls to evaluate their possible association with BC susceptibility. The XRCC3
      Met/Met genotype was associated with an increased BC risk (P = 0.003, OR = 2.44
      [95%CI 1.34-4.43]). We did not find an association between E233G polymorphism and
      BC risk. We also analyzed the effect of combined genotypes among RAD51-135G>C,
      Thr241Met, and E233G polymorphisms on BC risk. No interaction was observed
      between Thr241Met and 135G>C. The combined genotype Thr/Met-E/G was associated
      with an increased BC risk among women who (a) have a family history of BC, (b)
      are BRCA1/2-negative, and (c) were <50 years at onset (n = 195) (P = 0.037, OR =
      10.5 [95%CI 1.16-94.5]). Our results suggested that the variability of the DNA HR
      repair genes XRCC3 and RAD51D may play a role in BC risk, but this role may be
      underlined by a mutual interaction between these genes. These findings should be
      confirmed in other populations.

PMID- 20054643
TI  - Pre-operative assessment enables early diagnosis and recovery of shoulder
      function in patients with breast cancer.
AB  - In order to determine the extent and time course of upper limb impairment and
      dysfunction in women being treated for breast cancer (BC), and followed
      prospectively, a novel physical therapy surveillance model post-treatment was
      used. Subjects included adult women with newly diagnosed, untreated, unilateral,
      Stage I to III BC, and normal physiological and biomechanical shoulder function.
      Subjects were excluded if they had a previous history of BC, or prior injury or
      surgery of the affected upper limb. Measurements included body weight, shoulder
      ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and
      an upper limb disability questionnaire (ULDQ). Measurements were taken at
      baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects
      received pre-operative education and exercise instruction and specific physical
      therapy (PT) protocol after surgery including ROM and strengthening exercises.
      All measures of function were significantly reduced 1 month post-surgery, but
      most recovered to baseline levels by 1-year post-surgery. Some subjects developed
      signs of lymphedema 3-12 months post-surgery, but this did not compromise
      function. Shoulder abduction, flexion, and external rotation, but not internal
      rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing
      surgery for BC who receive PT intervention may expect a return to baseline ROM
      and strength by 3 months. Those who do not reach baseline, often continue to
      improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema
      develops independently of shoulder function 3-12 months post-surgery,
      necessitating continued monitoring. A prospective physical therapy model of
      surveillance allows for detection of early and later onset of impairment
      following surgery for BC in this specific cohort of patients.

PMID- 20054645
TI  - Estimation of natural history parameters of breast cancer based on non-randomized
      organized screening data: subsidiary analysis of effects of inter-screening
      interval, sensitivity, and attendance rate on reduction of advanced cancer.
AB  - Estimating the natural history parameters of breast cancer not only elucidates
      the disease progression but also make contributions to assessing the impact of
      inter-screening interval, sensitivity, and attendance rate on reducing advanced
      breast cancer. We applied three-state and five-state Markov models to data on a
      two-yearly routine mammography screening in Finland between 1988 and 2000. The
      mean sojourn time (MST) was computed from estimated transition parameters.
      Computer simulation was implemented to examine the effect of inter-screening
      interval, sensitivity, and attendance rate on reducing advanced breast cancers.
      In three-state model, the MST was 2.02 years, and the sensitivity for detecting
      preclinical breast cancer was 84.83%. In five-state model, the MST was 2.21 years
      for localized tumor and 0.82 year for non-localized tumor. Annual, biennial, and
      triennial screening programs can reduce 53, 37, and 28% of advanced cancer. The
      effectiveness of intensive screening with poor attendance is the same as that of
      infrequent screening with high attendance rate. We demonstrated how to estimate
      the natural history parameters using a service screening program and applied
      these parameters to assess the impact of inter-screening interval, sensitivity,
      and attendance rate on reducing advanced cancer. The proposed method makes
      contribution to further cost-effectiveness analysis. However, these findings had
      better be validated by using a further long-term follow-up data.

PMID- 20054646
TI  - New troglitazone derivatives devoid of PPARgamma agonist activity display an
      increased antiproliferative effect in both hormone-dependent and hormone
      independent breast cancer cell lines.
AB  - Numerous recent studies indicate that most anticancer effects of PPARgamma
      agonists like thiazolidinediones are the result of PPARgamma-independent
      pathways. These conclusions were obtained by several approaches including the use
      of thiazolidinedione derivatives like Delta2-Troglitazone (Delta2-TGZ) that does
      not activate PPARgamma. Since biotinylation has been proposed as a mechanism able
      to increase the specificity of drug delivery to cancer cells which could express
      a high level of vitamin receptor, a biotinylated derivative of Delta2-TGZ
      (bDelta2-TGZ) has been synthetized. In the present article, we have studied the
      in vitro effects of this molecule on both hormone-dependent (MCF-7) and hormone
      independent (MDA-MB-231) breast cancer cells. In both cell lines, bDelta2-TGZ was
      more efficient than Delta2-TGZ to decrease cell viability. bDelta2-TGZ was also
      more potent than Delta2-TGZ to induce the proteasomal degradation of cyclin D1 in
      both cell lines and those of ERalpha in MCF-7 cells. However, in competition
      experiments, the presence of free biotin in the culture medium did not decrease
      the antiproliferative action of bDelta2-TGZ. Besides, other compounds that had no
      biotin but that were substituted at the same position of the phenolic group of
      the chromane moiety of Delta2-TGZ decreased cell viability similarly to bDelta2
      TGZ. Hence, we concluded that the increased antiproliferative action of bDelta2
      TGZ was not due to biotin itself but to the functionalization of the terminal
      hydroxyl group. This should be taken into account for the design of new
      thiazolidinedione derivatives able to affect not only hormone-dependent but also
      hormone-independent breast cancer cells in a PPARgamma-independent pathway.

PMID- 20054647
TI  - A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients
      with metastatic breast cancer.
AB  - The purpose of this study was to determine the safety and maximum tolerated dose
      (MTD) of BZL101 (FDA IND# 59,521), an orally delivered aqueous extract from the
      herb Scutellaria barbata, in women with metastatic breast cancer (MBC). The trial
      was an open-label, phase 1B, multicenter, dose escalation study. Eligible
      patients had histologically confirmed breast cancer and measurable stage IV
      disease. The standard phase 1 "3 + 3" study design was used to determine the MTD.
      Primary endpoints were toxicity and MTD of BZL101. Secondary outcomes included
      efficacy based on RECIST criteria. A total of 27 women with a median of 2 prior
      chemotherapy treatments for metastatic disease were treated in four different
      dose cohorts. Grade 3 and 4 adverse events (AEs) were uncommon. Dose-limiting
      toxicities included the following: grade 4 AST elevation, grade 3 diarrhea, grade
      3 fatigue, and grade 3 rib pain. Fourteen patients were evaluable according to
      Response Evaluation Criteria in Solid Tumors. Investigator assessment classified
      three patients with stable disease for >120 days (21%). One patient was on BZL101
      for 449 days and remains stable for 700 + days. Independent radiology review
      identified three patients with objective tumor regression (>0% and <30%). The MTD
      was not reached, thus per protocol, the MTD was defined as the maximum
      administered dose of BZL101 40 g/day. In conclusion, oral administration of
      BZL101 was safe, well tolerated, and showed promising clinical evidence of
      anticancer activity in this heavily pretreated population of women with MBC.

PMID- 20054648
TI  - The effects of performance-based assessment criteria on student performance and
      self-assessment skills.
AB  - This study investigated the effect of performance-based versus competence-based
      assessment criteria on task performance and self-assessment skills among 39
      novice secondary vocational education students in the domain of nursing and care.
      In a performance-based assessment group students are provided with a preset list
      of performance-based assessment criteria, describing what students should do, for
      the task at hand. The performance-based group is compared to a competence-based
      assessment group in which students receive a preset list of competence-based
      assessment criteria, describing what students should be able to do. The test
      phase revealed that the performance-based group outperformed the competence-based
      group on test task performance. In addition, higher performance of the
      performance-based group was reached with lower reported mental effort during
      training, indicating a higher instructional efficiency for novice students.

PMID- 20054649
TI  - Modulation of carbohydrate metabolism during N-methyl N-nitrosourea induced
      neurotoxicity in mice: role of curcumin.
AB  - The present study was carried out to elucidate the effectiveness of curcumin in
      mitigating the adverse effects caused by N-Methyl N-Nitrosourea (MNU) on mouse
      cerebellum and cerebrum. Male laca mice received either intravenous MNU treatment
      at a dose of 10 mg/kg bw in sterile double distilled water, curcumin alone 60
      mg/kg bw in drinking water, or combined MNU and curcumin treatment on alternate
      days for a period of 2 months. The effects of different treatments were studied
      on carbohydrate metabolizing enzymes viz: hexokinase, glucose-6-phosphatase
      (G6P), glucose-6-isomerase (G6I), lactate dehydrogenase (LDH), succinate
      dehydrogenase (SDH) and glycogen levels. Curcumin supplementation to MNU treated
      mice was able to reduce significantly the activities of the G6P, G6I, hexokinase,
      LDH, SDH and increased the glycogen contents in both the regions of brain which
      were altered following MNU treatment. Hence, curcumin shall prove to be effective
      in ameliorating the adverse effects caused by MNU.

PMID- 20054650
TI  - A methodology for prediction of acute hypotensive episodes in ICU via a risk
      scoring model including analysis of ST-segment variations.
AB  - The aim of this study is to detect Acute Hypotensive Episodes (AHE) and Mean
      Arterial Pressure Dropping Regimes (MAPDRs) using ECG signal and Arterial Blood
      Pressure waveforms. To meet this end, the QRS complexes and end-systolic end
      diastolic pulses are first extracted using two innovative Modified Hilbert
      Transform-Based algorithms namely as ECGMHT and BPMHT. A new smoothing algorithm
      is next developed based on piecewise polynomial fitting to smooth the fast
      fluctuations observed in RR-tachogram, systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) trends. Afterwards, in order to consider the
      mutual influence of parameters on the evaluation of shock probability, a Sugeno
      Adaptive Network-based Fuzzy Inference System-ANFIS is trained using Hasdai et
      al. (J Am Coll Cardiol, 35: 136-143, 2000) parameters as input, with appropriate
      membership functions for each parameter. Using this network, it will be possible
      to incorporate the possible mutual influences between risk parameters such as
      heart rate, SBP, DBP, ST-segment episodes, age, gender, weight and some
      miscellaneous factors to the calculation of shock occurrence probability. In the
      next step, the proposed algorithm is applied to 15 subjects of the MIMIC II
      Database and AHE and MAPDRs (MAP <= 60 mmHg with a period of 30 min or more) are
      identified. As a result of this study, for a sequence of MAPDRs as long as 20 min
      or more, there will exist a consequent high peak with the duration of 3-4 min in
      the corresponding probability of cardiogenic shock diagram.

PMID- 20054652
TI  - AChE deficiency or inhibition decreases apoptosis and p53 expression and protects
      renal function after ischemia/reperfusion.
AB  - We recently reported that the expression of the synaptic form of
      acetylcholinesterase (AChE) is induced during apoptosis in various cell types in
      vitro. Here, we provide evidence to confirm that AChE is expressed during
      ischemia-reperfusion (I/R)-induced apoptosis in vivo. Renal I/R is a major cause
      of acute renal failure (ARF), resulting in injury and the eventual death of renal
      cells due to a combination of apoptosis and necrosis. Using AChE-deficient mice
      and AChE inhibitors, we investigated whether AChE deficiency or inhibition can
      protect against apoptosis caused by I/R in a murine kidney model. Unilateral
      clamping of renal pedicles for 90 min followed by reperfusion for 24 h caused
      significant renal dysfunction and injury. Both genetic AChE deficiency and
      chemical inhibition of AChE (provided by huperzine A, tacrine and donepezil)
      significantly reduced the biochemical and histological evidence of renal
      dysfunction following I/R. Activation of caspases-8, -9, -12, and -3 in vivo were
      prevented and associated with reduced levels of cell apoptosis and cell death. A
      further investigation also confirmed that AChE deficiency down-regulated p53
      induction and phosphorylation at serine-15, and decreased the Bax/Bcl-2 ratio
      during I/R. In conclusion, our study demonstrates that AChE may be a pro
      apoptotic factor and the inhibition of AChE reduces renal I/R injury. These
      findings suggest that AChE inhibitors may represent a therapeutic strategy for
      protection against ischemic acute renal failure.

PMID- 20054653
TI  - Nutrient based estimation of acid-base balance in vegetarians and non
      vegetarians.
AB  - A first objective of the present study was to estimate the acid-base balance of
      the food intake in vegetarians and non-vegetarians. A second objective was to
      evaluate if additional input of specific food items on the existing potential
      renal acid load (PRAL) list was necessary for the comparison of the two dietary
      patterns. Thirty vegetarians between the age of 18 and 30 years were matched for
      sex, age and BMI with 30 non-vegetarians. Based on the 3-days food diaries the
      acid-base status of the food intake was estimated using the PRAL method. Mean
      PRAL values as estimated with the standard table yielded an alkaline load of -5.4
      +/- 14.4 mEq/d in the vegetarians compared to an acid load of 10.3 +/- 14.4 mEq/d
      in the nonvegetarians (p<0.001). Mean PRAL values as estimated with the extended
      table yielded an alkaline load of -10.9 +/-19.7 mEq/d in the vegetarians compared
      to an acid load of 13.8 +/- 17.1 mEq/d for the non-vegetarians (p<0.001). The
      findings of this study indicate that vegetarian food intake produces more
      alkaline outcomes compared to non-vegetarian diets. The use of the standard PRAL
      table was sufficient for discrimination between the two diets.

PMID- 20054654
TI  - Focus ion beam micromachined glass pipettes   for cell microinjection.
AB  - Cell handling is currently hindered by rudimentary-manufactured manipulators.
      Restrictive designs of glass pipettes and other micromanipulators limit
      functionality and often damage cells, ultimately resulting in lysis. We present a
      novel technique to design and mill conventional glass pipettes at specifically
      chosen angles and geometries. Focus ion beam milling by Ga+ ions yields extremely
      polished edges. Results from mouse embryo piercing correlate increased
      penetration rates with decreased pipette angle. Milled pipettes maintain
      structural integrity after repeated piercing. For the first time, the effects of
      unintentionally implanted Ga+ on embryo development are addressed. Optimum embryo
      development up to blastocyst stage after manipulation reveal little impact of
      residual implanted Ga+, suggesting biocompatibility and paving the way to
      introducing ion milling techniques in the biomedical device arena. The milling
      technique can be adequately tailored to specific applications and allows for mass
      production, presenting a promising avenue for future, increasingly demanding,
      cell handling.

PMID- 20054655
TI  - Ophiostoma tsotsi sp. nov., a wound-infesting fungus of hardwood trees in Africa.
AB  - Polymorphic sequence-characterised marker assays from a recent diversity study on
      the Ascomycete fungus Ophiostoma quercus reported that some isolates from Africa
      were genetically distinct from O. quercus. In the present study, these African
      isolates were compared with authentic O. quercus isolates by evaluating
      morphological characters, growth in culture, mating compatibility and DNA
      sequence data. The isolates from Africa were morphologically similar to O.
      quercus, presenting Pesotum and Sporothrix synanamorphs in culture. Phylogenetic
      analyses of the ribosomal internal transcribed spacer regions 1 and 2, beta
      tubulin and translation elongation factor 1-alpha gene regions confirmed that the
      African group represents a distinct species within the hardwood lineage of the O.
      piceae complex, closely related to O. ulmi and O. himal-ulmi. Mating studies
      between O. quercus and the African isolates showed that isolates mated
      predominantly with those of their own group, although there were rare cases of
      fertile crosses between the groups. Isolates residing in the African lineage are
      described here as a new species, O. tsotsi sp. nov.

PMID- 20054656
TI  - The Functional Living Index-Cancer: estimating its reliability  based on clinical
      trial data.
AB  - PURPOSE: The Functional Living Index-Cancer was developed to measure quality of
      life in cancer trials as an adjunct to the usual clinical outcomes. The scale is
      considered conceptually good, since it covers a broad range of relevant aspects
      of quality of life, but the main criticism has been that its reliability has
      never been properly investigated. In this paper, we investigate the reliability
      of the FLIC. METHODS: We apply a new methodology based on linear mixed models
      that allows estimating reliability from real clinical data. The reliability of
      the FLIC is estimated using data coming from a longitudinal study in breast
      cancer. With this new approach, we avoid the need for additional data collection
      on which classical reliability studies are based. RESULTS: The average
      reliability of the FLIC over the repeated measurements is satisfactory, even
      though the initial measurement in the study showed a somewhat lower value. Taking
      into account the longitudinal character of the measurements, we show that highly
      reliable information can be obtained with a relatively small number of
      measurements per patient. CONCLUSION: The FLIC provides reliable quality of life
      measurements in patients with breast cancer. Additional studies would be welcome
      to validate these results in other populations.

PMID- 20054657
TI  - A new familial cancer syndrome including predisposition to Wilms tumor and
      neuroblastoma.
AB  - Wilms tumor and neuroblastoma are childhood tumors of the kidney and
      undifferentiated neural crest cells, respectively. Both disorders are primarily
      sporadic, but familial Wilms tumor pedigrees and familial neuroblastoma pedigrees
      are each well recognized and account for approximately 1-3% of each tumor type.
      Families with Wilms tumor and neuroblastoma in the same, or related individuals,
      have not been reported. Here, we present nine families with two or more
      individuals with Wilms tumor and/or neuroblastoma. The affected individuals were
      otherwise well, without syndromic features. Although this co-occurrence might be
      due to chance in some families, the coexistence of two rare embryonal tumors in
      related individuals of multiple families suggests an underlying genetic
      susceptibility to both tumors. We undertook mutational analysis of the genes
      known to predispose to non-syndromic familial Wilms tumor (WT1) or neuroblastoma
      (PHOX2B, ALK) which excluded these as the underlying predisposition genes in the
      nine families. We also excluded epigenetic and copy-number abnormalities at 11p15
      which are known to predispose to embryonal tumors including Wilms tumor and
      neuroblastoma. Overall, these data suggest that families with both Wilms tumor
      and neuroblastoma represent a previously unrecognized familial cancer syndrome in
      which the underlying predisposition gene(s) remain to be determined.

PMID- 20054658
TI  - LOH analysis should not be used as a tool to assess whether UVs of BRCA1/2 are
      pathogenic or not.

PMID- 20054659
TI  - Success and complication rates of two precut techniques, transpancreatic
      sphincterotomy and needle-knife sphincterotomy for bile duct cannulation.
AB  - BACKGROUND: The majority of literature on the precut technique is concerned with
      needle-knife sphincterotomy, whereas the comparison of transpancreatic
      sphincterotomy and needle-knife sphincterotomy has been rarely reported. Aim The
      aim of the study was to compare the success and the complication rates of
      transpancreatic sphincterotomy with needle-knife sphincterotomy. METHODS: During
      May 2006 and April 2007, 3,178 consecutive endoscopic retrograde
      cholangiopancreatography (ERCP) procedures were performed in a prospective
      multicenter study on ERCP-related complications. From the files of these
      patients, data of cases undergoing precut sphincterotomy, including
      transpancreatic sphincterotomy and needle-knife sphincterotomy, were
      retrospectively extracted and analyzed. RESULTS: Overall, 216 patients with
      precut sphincterotomy were identified; 140 cases received transpancreatic
      sphincterotomy, and 76 received needle-knife sphincterotomy. There was no
      significant difference in the initial and eventual success rates between
      transpancreatic and needle-knife sphincterotomy (82.9% vs. 90.8% and 90.0% vs.
      90.8%, respectively). The overall incidences of complications and acute
      pancreatitis were not significantly different between the two groups (14.3% vs.
      18.4% and 11.4% vs. 11.8%, respectively).

PMID- 20054660
TI  - Peng's binding pancreaticojejunostomy after pancreaticoduodenectomy: a French
      prospective study.
AB  - BACKGROUND: Pancreatic fistula (PF) is the single most important complication
      after pancreaticoduodenectomy. Recently, a 0% rate of PF was reported using a
      binding pancreaticojejunostomy with intussusception of the pancreatic stump. The
      aim of this study was to assess the safety of this new binding
      pancreaticojejunostomy in condition most susceptible to PF, i.e. soft pancreas
      and non-dilated main pancreatic duct. METHODS: Forty-five consecutive patients
      with soft pancreas and non-dilated main pancreatic duct underwent a binding
      pancreaticojejunostomy. Post-operative PF was defined according to the
      International Study Group of Pancreatic Fistula. RESULTS: Four patients (8.9%)
      developed a PF. In one case, PF developed on post-operative day 3 due to a
      technical deficiency. In the three other cases, pancreatic fistula developed
      after the tenth post-operative day; all the patients had local and/or general co
      morbidities before PF occurrence. CONCLUSIONS: Binding pancreaticojejunostomy
      according to Peng is a safe and secure technique that improves the rate of
      pancreatic fistula, especially in case of soft texture of the pancreas remnant.
      However, a 0% rate seems to be hard to achieve because other abdominal and
      general complications are frequent and can lead to secondary leakage of the
      pancreatic anastomosis.

PMID- 20054661
TI  - Obesity and disability in the symptomatic Irish knee osteoarthritis population.
AB  - BACKGROUND: Osteoarthritis (OA) of the knee is a common disorder with significant
      social and financial implications. Obesity is the strongest modifiable risk
      factor of knee OA. There is little data on obesity in Irish knee OA populations
      and its relationship to other measures of disease severity. AIMS: In Beaumont
      Hospital, we have been collecting data on patients presenting with knee OA as
      part of a screening process for potential candidates for therapeutic exercise
      intervention studies. Here, we present data on the first 96 candidates screened
      during this process. RESULTS: The mean body mass index (BMI) of the group fell
      within the obese range (31); indeed, only 21% had a normal BMI. The vast majority
      of our patients had severe self-reported disability. In contrast, the
      distribution of radiographic severity of knee OA was more even. There was no
      significant relationship between radiographic severity and disability. BMI did
      predict disability but had a weak correlation. Radiographic severity did not
      correlate with BMI. CONCLUSION: Irish patients with knee OA referred for
      physiotherapy were very disabled, significantly obese and represent a challenging
      cohort of patients to treat.

PMID- 20054662
TI  - Effect of endemic fluorosis on hematological parameters.
AB  - Although so many studies exist on effect of fluoride on hematological parameters
      in experimental animals, a few studies have been conducted to investigate the
      effects of chronic fluorosis on hematological parameters in humans' subjects with
      endemic fluorosis. So we aimed to determine the hematological parameters in
      patients with endemic fluorosis. The study group consisted of 60 patients with
      endemic fluorosis (27 females, 33 males, and mean age 33.4 +/- 9.6 years). An age
      , gender-, and body mass index-matched control group was composed of 34 healthy
      volunteers (11 females, 23 males with a mean age 32.6 +/- 5.6 years). Urine
      fluoride levels of fluorosis patients were significantly higher than control
      subjects as expected (0.42 +/- 0.09 vs 1.92 +/- 0.14 mg/l, respectively; P <
      0.001). There were no statistically significant differences between the fluorosis
      group and control group with respect to hematological parameters (complete blood
      count and ferritin). We concluded that chronic fluorosis has no effect on
      hematological parameters in patients with endemic fluorosis.

PMID- 20054663
TI  - Developmental iodine deficiency and hypothyroidism reduce phosphorylation of
      calcium/calmodulin-dependent kinase II in the rat entorhinal cortex.
AB  - Iodine is essential for the synthesis of triiodothyronine (T3) and thyroxine
      (T4). Iodine deficiency leads to inadequate thyroid hormone. Hypothyroidism
      induced by iodine deficiency during gestation and postnatal period leads to
      cognitive deficits in learning and memory. However, the mechanism underlying
      these deficits is unclear. Calcium-dependent calmodulin kinase II (CaMKII) known
      as a potential memory molecule regulates important neuronal functions including
      learning and memory. Recent studies have shown that hypothyroidism alters
      phosphorylation of CaMKII in hippocampus or even in sympathetic ganglia of rats.
      Though the entorhinal cortex (EC) is an important functional structure within the
      neuronal network responsible for learning and memory, little is known about the
      effect of hypothyroidism on phosphorylation of CaMKII in the EC. Here, we report
      that iodine deficiency and propylthiouracil treatment through gestation and
      lactation reduce phosphorylation of CaMKII in the EC of pups. The increase of
      calcineurin, as well as reduction of neurogranin and calmodulin, may account for
      the reduced phosphorylation of CaMKII induced by developmental iodine deficiency
      and hypothyroidism. These findings in the EC may contribute to understanding the
      mechanisms that underlie impairment of learning and memory induced by
      developmental iodine deficiency and hypothyroidism.

PMID- 20054664
TI  - Glucose oxidase-dextran conjugates with enhanced stabilities against temperature
      and pH.
AB  - Multipoint covalent bonding of glucose oxidase (EC 1.1.3.4) to hydrophilic
      natural polymer dextran and optimization of procedures to obtain, with enhanced
      temperature and pH stabilities, were studied. Purified enzyme was conjugated with
      various molecular weight dextrans (17.5, 75, and 188 kD) in a ratio of 20:1,
      10:1, 1:1, 1:5, 1:10, 1:15, and 1:20. After 1 h of incubation at pH 7, the
      activities of purified enzyme and conjugates were determined at different
      temperatures (25 degrees C, 30 degrees C, 35 degrees C, 40 degrees C, 50 degrees
      C, 60 degrees C, 70 degrees C, and 80 degrees C), and the results were evaluated
      for thermal resistance. Increases in temperature from 25 degrees C to 50 degrees
      C did not change the activities of the conjugates. The conjugate, which was
      prepared with 75 kDa dextran in a molar ratio of 1:5, showed the highest thermal
      resistance and even the activity still remains at 80 degrees C at pH 7.0. This
      conjugate also displayed activity in a wide pH range (pH 4.0-7.0) at high
      temperatures. Conjugate, which was synthesized with 75 kDa dextran in a molar
      ratio of 1:5, appears to be feasible and useful for biotechnological
      applications.

PMID- 20054665
TI  - Erratum to: Access to Adequate Outpatient Depression Care for Mothers in the USA:
      A Nationally Representative Population-Based Study.

PMID- 20054666
TI  - Magnetic propulsion of a magnetic device using three  square-Helmholtz coils and
      a square-Maxwell coil.
AB  - We introduce a square coil system for remote magnetic navigation of a magnetic
      device without any physical movements of the coils. We used three square
      Helmholtz coils and a square-Maxwell coil for magnetic propulsion of a small
      magnet along the desired path. All the square coils are mountable on a cubic
      frame that has an opening to accommodate a living subject. The square-Helmholtz
      coils control the magnetic propulsion direction by generating uniform magnetic
      field along the desired direction while the square-Maxwell coil controls the
      propulsion force by generating magnetic gradient field. We performed magnetic
      propulsion experiments with a down-scaled coil set and a three-channel coil
      driver. Experimental results demonstrate that we can use the square coil set for
      magnetic navigation of a magnetic device without any physical movements of the
      coils.

PMID- 20054667
TI  - Development of a quantitative competitive reverse transcription polymerase chain
      reaction (QC-RT-PCR) for detection and quantitation of Chikungunya virus.
AB  - Chikungunya is one of the most important emerging arboviral infections of public
      health significance. Due to lack of a licensed vaccine, rapid diagnosis plays an
      important role in early management of patients. In this study, a QC-RT-PCR assay
      was developed to quantify Chikungunya virus (CHIKV) RNA by targeting the
      conserved region of E1 gene. A competitor molecule containing an internal
      insertion was generated, which provided a stringent control of the quantification
      process. The introduction of 10-fold serially diluted competitor in each reaction
      was further used to determine sensitivity. The applicability of this assay for
      quantification of CHIKV RNA was evaluated with human clinical samples, and the
      results were compared with real-time quantitative RT-PCR. The sensitivity of this
      assay was estimated to be 100 RNA copies per reaction with a dynamic detection
      range of 10(2) to 10(10) copies. Specificity was confirmed using closely related
      alpha and flaviviruses. The comparison of QC-RT-PCR result with real-time RT-PCR
      revealed 100% concordance for the detection of CHIKV in clinical samples. These
      findings demonstrated that the reported assay is convenient, sensitive and
      accurate method and has the potential usefulness for clinical diagnosis due to
      simultaneous detection and quantification of CHIKV in acute-phase serum samples.

PMID- 20054668
TI  - Pivotal role of ADAMTS13 function in liver diseases.
AB  - The liver is a major source of clotting and fibrinolytic proteins, and plays a
      central role in thrombo-regulation. Patients with advanced liver diseases tend to
      bleed because of reduced plasma levels of several clotting factors and
      thrombocytopenia, but they do also exhibit thrombotic complications. ADAMTS13 is
      a metalloproteinase, produced exclusively in hepatic stellate cells, and
      specifically cleaves highly multimeric von Willebrand factor (VWF). VWF plays a
      pivotal role in hemostasis and thrombosis, and its function is dependent on its
      multimeric state. Deficiency of ADAMTS13 results in accumulation of unusually
      large VWF multimers (UL-VWFM) in plasma, in turn induces platelet clumping or
      thrombi under high shear stress, followed by microcirculatory disturbances.
      Considering that UL-VWFM, the substrate of ADAMTS13, is produced in transformed
      vascular endothelial cells at sites of liver injury, decreased ADAMTS13 activity
      may be involved in not only sinusoidal microcirculatory disturbances, but also
      subsequent progression of liver injuries, eventually leading to multiorgan
      failure. This concept can be applied to the development or aggravation of liver
      diseases, including liver cirrhosis, alcoholic hepatitis, veno-occlusive disease,
      and adverse events after liver transplantation. These results promise to bring
      further understanding of the pathophysiology of liver diseases, and offer new
      insight for development of therapeutic strategies.

PMID- 20054669
TI  - Randomized trial of response-oriented individualized versus   fixed-schedule
      induction chemotherapy with idarubicin   and cytarabine in adult acute myeloid
      leukemia:   the JALSG AML95 study.
AB  - A multicenter, prospective, randomized study was conducted to compare a response
      oriented individualized remission induction therapy with a standard fixed
      schedule induction therapy, using idarubicin (IDR) and cytarabine (Ara-C), in
      adult patients with acute myeloid leukemia (AML). Newly diagnosed patients with
      AML of age less than 65 were randomly assigned to receive either of the two
      schedules. Both groups received IDR (12 mg/m2) for 3 days and Ara-C (100 mg/m2)
      for 7 days. In the individualized group, if the bone marrow on day 8 did not
      become hypocellular with less than 15% blasts, patients received additional IDR
      for one more day and Ara-C for 2 or 3 more days. Patients achieving complete
      remission (CR) received the same post-remission therapy. The CR rate was 79.4%
      for the individualized group (n = 209) and 81.9% for the fixed group (n = 221) (p
      = 0.598). At a median follow-up of 81 months, 7-year predicted overall survival
      was 37% for the individualized group and 39% for the fixed group (p = 0.496), and
      7-year predicted event-free survival was 22% for the individualized group and 23%
      for the fixed group (p = 0.546). Thus, the present study could not demonstrate
      any advantage of a response-oriented individualized induction therapy over a
      fixed-schedule induction therapy in this protocol setting.

PMID- 20054670
TI  - Failure of copy Imatib (CIPLA, India) to maintain hematologic and cytogenetic
      responses in chronic myeloid leukemia in chronic phase.
AB  - A 50-year-old woman presented with CML-CP and was initially treated with branded
      imatinib (Glivec) 400 mg/day. She rapidly achieved a complete hematologic
      response (CHR), at which point she switched therapy to a copy version of imatinib
      (Imatib). She received 400 mg/day of Imatib for 3 months, during which time her
      platelet count decreased from 250 x 10(9) to 105 x 10(9)/L and her hemoglobin
      count fell from 12.8 to 11 g/dL. The patient's total leukocyte count rose rapidly
      from 4 x 10(9) to 70 x 10(9)/L, and the CHR was lost. At this point, therapy was
      switched back to Glivec at 400 mg/day, and the CHR was rapidly regained.
      Furthermore, the patient achieved a major cytogenetic response by 6 months after
      reintroduction of Glivec. This case report suggests a difference in clinical
      efficacy between the authorized form of imatinib (Glivec) and the copy version of
      the drug (Imatib). The exact reasons for the observed difference in clinical
      efficacy are unknown, but likely relate to the use of alternative polymorphic
      forms of the drug. Glivec can be obtained directly from the manufacturer
      (Novartis Pharmaceuticals) through a variety of patient access programs that
      should be fully explored when needed.

PMID- 20054671
TI  - Sustained release tablets containing soluble polymethacrylates: comparison with
      tableted polymethacrylate IPEC polymers.
AB  - The objective of this study was to compare a novel sustained release tablet
      formulation that has the potential to be used for drugs of different
      physicochemical properties using a binary mixture of polymethacrylate polymers in
      their salt forms with the polymethacrylate interpolyelectrolyte complex (IPEC)
      tablets in terms of drug release and compactness. Also, we aimed to compare this
      formulation with an IPEC tablet in terms of drug release. Tablets prepared using
      Eudragit E-Citrate and Eudragit L-Sodium were more convenient, easier to prepare,
      and showed better sustained release and compactness characteristics compared to
      IPEC tablets of similar concentrations and preparation methods.

PMID- 20054673
TI  - No recurrences in selected patients after curettage with cryotherapy for grade I
      chondrosarcomas.
AB  - BACKGROUND: The low aggressiveness of Grade I chondrosarcomas is compatible with
      conservative surgical treatment. QUESTIONS/PURPOSE: We asked whether combined
      curettage and cryotherapy would yield low rates of recurrence and whether
      supplemental internal fixation would retain function with low rates of
      complications in patients with Grade I central chondrosarcomas of the proximal
      humerus or distal femur. METHODS: We retrospectively reviewed 15 patients: nine
      women and six men with a mean age of 45 years (range, 26-70 years). All patients
      underwent curettage and cryosurgery through a cortical window; we replaced the
      window and plated the region with at least three screws beyond the curetted area.
      None of the patients was lost to followup, and 14 patients (93%) were reexamined
      by us after a minimum of 5 years (mean, 8 years; range, 5-11 years). RESULTS:
      There were no perioperative anesthetic, neurologic, hardware, or healing
      complications. None of the patients had local recurrence or metastases develop.
      At last followup, the Musculoskeletal Tumor Society score was 27.9 (range, 22-30)
      and all patients had resumed their previous activities. No complications were
      associated with this simplified cryotherapy technique. CONCLUSIONS: The data
      confirm the appropriateness of conservative surgery for central low-grade
      chondrosarcomas of the proximal humerus and distal femur based on a combination
      of intralesional curettage and cryogenic parietal sterilization. Candidates for
      this approach should be chosen on the basis of the affected bone site, local
      extension staging, and clinicopathologic grading. We recommend supplementary
      internal fixation. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 20054674
TI  - MRI-guided navigation surgery with temporary implantable bone markers in limb
      salvage for sarcoma.
AB  - BACKGROUND: Technical errors during navigation-assisted bone tumor resection may
      occur by: (1) incorrect registration of images and corresponding anatomic points
      of bone sent to the navigation system; and (2) incorrect fusion of two or more
      images that have been transported to the navigation system. QUESTIONS/PURPOSES:
      We investigated new methods of navigation surgery to minimize technical errors
      during the registration and image fusion processes and specifically asked whether
      a navigated cannula probe would reduce unnecessary soft tissue dissection, and
      allow percutaneous registration and implantation of a reference base tracker in
      the margin of bone to be resected. METHODS: We performed direct MRI-guided
      navigation surgery without image fusion on a patient with osteosarcoma using
      absorbable pins as temporary implanted bone markers that prevent artifacts on MR
      images. RESULTS: Direct MRI-guided navigation surgery was possible using bone
      markers. A navigated cannula probe allowed percutaneous registration and a
      navigated blade-shaped probe provided a real-time check on the narrow osteotomy
      gap. The surgical procedure was facilitated by implantation of a reference base
      tracker on the margin of bone to be resected. CONCLUSIONS: Our modified technique
      of MRI-guided navigation surgery for patients with a malignant bone tumor may
      reduce processing errors by increased accuracy and be helpful for joint
      preserving surgery.

PMID- 20054675
TI  - Case report: calcific tendinitis of the rectus femoris: a rare cause of snapping
      hip.
AB  - BACKGROUND: Internal snapping hip is a syndrome caused by recurrent subluxation
      of the iliopsoas tendon. There is little agreement regarding the impinging sites
      responsible for the jerky motion of the tendon. Thus far, the lesser trochanter,
      anterior capsule, and iliopectineal eminence are considered the most likely
      catching sites. CASE DESCRIPTION: We report an unusual case in which a calcific
      tendinitis of the rectus femoris direct head impinged against the overlying
      iliacus muscle, resulting in a painful coxa saltans. The exclusive involvement of
      the direct head hid the calcium deposit on standard radiographs, whereas MRI
      suggested but poorly showed the tendon disease. Dynamic ultrasonography and CT
      scanning allowed a precise diagnosis and subsequent treatment with CT-guided
      steroid injection. LITERATURE REVIEW: Calcific tendinitis of the rectus anterior
      direct head has not been reported as a possible cause of snapping hip;
      involvement of the direct head in rectus anterior calcific tendinitis was
      described in one case. PURPOSES AND CLINICAL RELEVANCE: Our case shows the rectus
      anterior direct head may be involved in the etiology of coxa saltans.
      Theoretically any thickening of the tendon might activate the same
      pathomechanism. Physicians should consider this possible new cause of internal
      snapping hip when the most common ones have been excluded, especially as it may
      be managed easily with steroid injection.

PMID- 20054676
TI  - Leisure time physical activity and sedentary behavior and substance use among in
      school adolescents in eight African countries.
AB  - BACKGROUND: Physical inactivity leads to higher morbidity and mortality from
      chronic non-communicable diseases. In high income countries, studies have
      measured school population level physical activity and substance use, but
      comparable data are lacking from most African countries. PURPOSE: To study the
      relationship between self-reported leisure time physical activity frequency and
      sedentary behavior and alcohol, tobacco, and other drug use behaviors among
      school children. METHOD: A cross-sectional survey was conducted with the total
      sample of 24,593 school children aged 13 to 15 years from nationally
      representative samples from eight African countries. Univariate and multivariate
      analyses were conducted to assess the relationship between physical activity
      frequency, six measures of alcohol, tobacco, and other drug use, socioeconomic
      status, and mental health variables. RESULTS: In all, only 14.2% of the school
      children were frequently physically active (5 days and more in a week, at least
      60 min/day) during leisure time; this was significantly higher among boys than
      girls. Ugandan and Kenyan school children were most physically active (17.7% and
      16.0%, respectively), and Zambian and Senegalese the least (9.0% and 10.9%,
      respectively). Frequency of alcohol consumption and higher socioeconomic status
      were significantly associated with leisure time physical activity, while tobacco,
      illicit drug use, and mental health variables were not. Leisure time sedentary
      behavior of five and more hours spent sitting on a usual day were highly
      associated with all substance use variables. CONCLUSION: These findings suggest
      that leisure time physical activity frequency is associated with frequency of
      alcohol use and not with tobacco and illicit drug use, and leisure time sedentary
      behavior is highly associated with alcohol, tobacco, and drug use among
      adolescents.

PMID- 20054677
TI  - [Vacuoles: a hollow threat?].

PMID- 20054678
TI  - Treatment of complex regional pain syndrome: a review of the evidence.
AB  - PURPOSE: This narrative review summarizes the evidence derived from randomized
      controlled trials pertaining to the treatment of complex regional pain syndrome
      (CRPS). SOURCE: Using the MEDLINE (January 1950 to April 2009) and EMBASE
      (January 1980 to April 2009) databases, the following medical subject headings
      (MeSH) were searched: "Complex Regional Pain Syndrome", "Reflex Sympathetic
      Dystrophy", and "causalgia" as well as the key words "algodystrophy", "Sudeck's
      atrophy", "shoulder hand syndrome", "neurodystrophy", "neuroalgodystrophy",
      "reflex neuromuscular dystrophy", and "posttraumatic dystrophy". Results were
      limited to randomized controlled trials (RCTs) conducted on human subjects,
      written in English, published in peer-reviewed journals, and pertinent to
      treatment. PRINCIPAL FINDINGS: The search criteria yielded 41 RCTs with a mean of
      31.7 subjects per study. Blinded assessment and sample size justification were
      provided in 70.7% and 19.5% of RCTs, respectively. Only biphosphonates appear to
      offer clear benefits for patients with CRPS. Improvement has been reported with
      dimethyl sulfoxide, steroids, epidural clonidine, intrathecal baclofen, spinal
      cord stimulation, and motor imagery programs, but further trials are required.
      The available evidence does not support the use of calcitonin, vasodilators, or
      sympatholytic and neuromodulative intravenous regional blockade. Clear benefits
      have not been reported with stellate/lumbar sympathetic blocks, mannitol,
      gabapentin, and physical/occupational therapy. CONCLUSIONS: Published RCTs can
      only provide limited evidence to formulate recommendations for treatment of CRPS.
      In this review, no study was excluded based on factors such as sample size
      justification, statistical power, blinding, definition of intervention
      allocation, or clinical outcomes. Thus, evidence derived from "weaker" trials may
      be overemphasized. Further well-designed RCTs are warranted.

PMID- 20054679
TI  - Routine preoperative electrocardiogram and chest x-ray prior to elective surgery
      in Alberta, Canada.
AB  - PURPOSE: A study was undertaken to evaluate the utilization rates of routine
      preoperative electrocardiogram (ECG) and chest x-ray (CXR) by sex, age, and most
      frequent surgery type, and to estimate the total cost of these screening tests.
      METHODS: We included all patients undergoing elective surgery in Alberta from
      April 1, 2005 to March 31, 2007, except those with a cancer, trauma, or cardiac
      diagnosis. The utilization rate was equal to the number of tests divided by the
      number of elective surgeries. The total cost of the tests was estimated in
      Canadian dollars under a health care perspective and was equal to the number of
      tests multiplied by the cost per test. RESULTS: With utilization rates of 13.4%
      and 23.2%, routine preoperative ECG and CXR tests cost Alberta about $369,000 and
      $637,000 over 2 yrs, respectively. More than 80% of the cost was incurred by
      tests on patients aged 50 or older. The utilization rates of tests vary
      considerably among the most frequent surgeries, but not between men and women.
      CONCLUSIONS: Routine preoperative testing rates and costs are relatively low in
      Alberta. It is possible that general evidence widely disseminated over the past
      number of years regarding unnecessary routines in preoperative testing has had an
      effect. Further interventions to reduce them would be of little value.

PMID- 20054680
TI  - Does ultrasound-guided infraclavicular block meet users' expectations?

PMID- 20054681
TI  - High-fidelity simulation in anesthesiology training: a survey of Canadian
      anesthesiology residents' simulator experience.
AB  - PURPOSE: The objective of this survey was to explore Canadian anesthesiology
      residents' educational experience with high-fidelity simulation and to improve
      understanding of the factors perceived to have either a positive or a negative
      effect on residents' learning. METHODS: In 2008, all Canadian anesthesiology
      residents (n = 599) were invited to complete a ten-minute anonymous online
      survey. Survey questions were derived from two sources, a literature search of
      MEDLINE (1966 to present), EMBASE (1980 to present), and the Cochrane and
      Campbell collaboration libraries and the experience of 25 pilot residents and the
      lead author. RESULTS: The survey response rate was 27.9% (n = 167). Junior
      residents (PGY1-3) responded that it would be helpful to have an introductory
      simulation course dealing with common intraoperative emergencies. The
      introduction of multidisciplinary scenarios (where nurses and colleagues from
      different specialties were involved in scenarios) was strongly supported. With
      respect to gender, male anesthesia residents indicated their comfort in making
      mistakes and asking for help in the simulator more frequently than female
      residents. In accordance with the ten Best Evidence Medical Education (BEME)
      principles of successful simulator education, Canadian centres could improve
      residents' opportunities for repetitive practice (with feedback),
      individualization of scenarios, and defined learning outcomes for scenarios.
      DISCUSSION: Anesthesiology residents indicate that simulation-based education is
      an anxiety provoking experience, but value its role in promoting safe practice
      and enhancing one's ability to deal with emergency situations. Suggestions to
      improve simulation training include increasing residents' access, adopting a more
      student-centred approach to learning, and creating a safer learning environment.

PMID- 20054682
TI  - Peripheral nerve catheter entrapment is not always related to knotting.

PMID- 20054683
TI  - Vacuolar ATPase-mediated sequestration of local anesthetics in swollen
      macroautophagosomes.
AB  - PURPOSE: Local anesthetics in their therapeutic concentration range cause a
      vacuolar cytopathology that has been observed in vivo and in various types of
      mammalian cells. We examined whether active concentration ranges of drugs and the
      kinetics of the vacuolar response are clinically relevant and whether this
      phenomenon is associated with cytotoxicity, autophagy, and cell stress
      signalling. METHODS: We compared procaine and lidocaine for morphological,
      functional, and signalling responses in a previously exploited non-neuronal
      system, primary smooth muscle cells. Several markers conjugated to fluorescent
      proteins allowed morphological and functional analysis of vacuolar cells.
      Signalling related to autophagy and cell stress was addressed (immunoblotting of
      cell lysates). RESULTS: Within 2-4 hr, lidocaine and procaine (> or = 1 mM)
      induced massive cell vacuolization, a response abated by the V-ATPase inhibitor,
      bafilomycin A1, and activated macroautophagic signalling (LC3 II formation) but
      not other stress signalling (p38, ERK1/2, p53, no influence on serum-controlled
      Akt phosphorylation). Novel aspects of the morphological analysis include reduced
      LC3 labelling of the large vacuoles in cells treated with 3-methyl-adenine,
      inhibition of CD63 labelling of these vacuoles by co-expression of dominant
      negative Rab7, retention of secretory green fluorescent protein (GFP) possessing
      a signal sequence in vacuolar cells, and partial vacuole labelling with lysosomal
      associated membrane protein 1 (LAMP1). Lidocaine (2.5-5 mM) was not overtly
      cytotoxic but arrested cell division over 48 hr. CONCLUSIONS: V-ATPase-mediated
      sequestration of clinically relevant concentrations of local anesthetics
      sequentially involves vacuolization, macroautophagic signalling, and lysosome
      fusion to large vacuoles. Disruption of the secretory pathway and mitotic arrest
      were also observed over several hours without major cytotoxicity.

PMID- 20054684
TI  - Identification of protein kinase disruptions as suppressors of the calcium
      sensitivity of S. cerevisiae Deltaptp2 Deltamsg5 protein phosphatase double
      disruptant.
AB  - The double disruptant of the S. cerevisiae protein phosphatase (PPase) genes,
      PTP2 (phosphotyrosine-specific PPase) and MSG5 (phosphotyrosine and
      phosphothreonine/serine-PPase) causes calcium-sensitive growth (Cas). Previous
      study using Fluorescent-activated cell sorting (FACS) analysis showed that this
      growth defect with calcium occurs at G1-S transition in the cell cycle. We
      discovered that six non-essential protein kinase (PKase) disruptions (Deltabck1,
      Deltamkk1, Deltaslt2/Deltampk1, Deltamck1, Deltassk2 and Deltayak1) suppressed
      the Cas-phenotype of the Deltaptp2 Deltamsg5 double disruptant. Bck1p, Mkk1p and
      Slt2p are components of the mitogen-activated protein kinase (MAPK) cascade of
      cell wall integrity pathway (Slt2 pathway), and Mck1p is its down regulator.
      Ssk2p is the MAPK kinase kinase of the high-osmolarity glycerol (HOG) pathway,
      while Yak1p is a negative regulator for the cAMP-dependent PKA pathway. FACS
      analysis revealed that only the disruption of Deltassk2 and Deltayak1 but not
      Deltabck1, Deltamkk1, Deltaslt2 and Deltamck1 was able to suppress the delayed G1
      S transition, suggesting that suppression of the growth defect is not always
      accompanied by suppression of the G1-S transition delay. The discovery of these
      PKases as suppressors revealed that in addition to the previously anticipated
      Slt2 pathway, HOG, Yak1p and Mck1p regulatory pathways may also be involved in
      the calcium sensitivity of the Deltaptp2 Deltamsg5 double disruptant.

PMID- 20054685
TI  - Diffusion tensor imaging (DTI) and tractography of the brachial plexus:
      feasibility and initial experience in neoplastic conditions.
AB  - INTRODUCTION: The objective of this study was to assess the feasibility and
      potential clinical applications of diffusion tensor imaging (DTI) and
      tractography in the normal and pathologic brachial plexus prospectively. METHODS:
      Six asymptomatic volunteers and 12 patients with symptoms related to the brachial
      plexus underwent DTI on a 1.5T system in addition to the routine anatomic plexus
      imaging protocol. Maps of the apparent diffusion coefficient (ADC) and of
      fractional anisotropy (FA), as well as tractography of the brachial plexus were
      obtained. Images were evaluated by two experienced neuroradiologists in a
      prospective fashion. Three patients underwent surgery, and nine patients
      underwent conservative medical treatment. RESULTS: Reconstructed DTI (17/18) were
      of good quality (one case could not be reconstructed due to artifacts). In all
      volunteers and in 11 patients, the roots and the trunks were clearly delineated
      with tractography. Mean FA and mean ADC values were as follows: 0.30+/-0.079 and
      1.70+/-0.35 mm2/s in normal fibers, 0.22+/-0.04 and 1.49+/-0.49 mm2/s in benign
      neurogenic tumors, and 0.24+/-0.08 and 1.51+/-0.52 mm2/s in malignant tumors,
      respectively. Although there was no statistically significant difference in FA
      and ADC values of normal fibers and fibers at the level of pathology,
      tractography revealed major differences regarding fiber architecture. In benign
      neurogenic tumors (n=4), tractography revealed fiber displacement alone (n=2) or
      fiber displacement and encasement by the tumor (n=2), whereas in the malignant
      tumors, either fiber disruption/destruction with complete disorganization (n=6)
      or fiber displacement (n=1) were seen. In patients with fiber displacement alone,
      surgery confirmed the tractography findings, and excision was successful without
      sequelae. CONCLUSION: Our preliminary data suggest that DTI with tractography is
      feasible in a clinical routine setting. DTI may demonstrate normal tracts, tract
      displacement, deformation, infiltration, disruption, and disorganization of
      fibers due to tumors located within or along the brachial plexus, therefore,
      yielding additional information to the current standard anatomic imaging
      protocols.

PMID- 20054686
TI  - Membrane-based actuation for high-speed single molecule force spectroscopy
      studies using AFM.
AB  - Atomic force microscopy (AFM)-based dynamic force spectroscopy of single
      molecular interactions involves characterizing unbinding/unfolding force
      distributions over a range of pulling speeds. Owing to their size and stiffness,
      AFM cantilevers are adversely affected by hydrodynamic forces, especially at
      pulling speeds >10 microm/s, when the viscous drag becomes comparable to the
      unbinding/unfolding forces. To circumvent these adverse effects, we have
      fabricated polymer-based membranes capable of actuating commercial AFM
      cantilevers at speeds >or=100 microm/s with minimal viscous drag effects. We have
      used FLUENT, a computational fluid dynamics (CFD) software, to simulate high
      speed pulling and fast actuation of AFM cantilevers and membranes in different
      experimental configurations. The simulation results support the experimental
      findings on a variety of commercial AFM cantilevers and predict significant
      reduction in drag forces when membrane actuators are used. Unbinding force
      experiments involving human antibodies using these membranes demonstrate that it
      is possible to achieve bond loading rates >or=10(6) pN/s, an order of magnitude
      greater than that reported with commercial AFM cantilevers and systems.

PMID- 20054687
TI  - Structural modeling of calcium binding in the selectivity filter of the L-type
      calcium channel.
AB  - Calcium channels play crucial physiological roles. In the absence of high
      resolution structures of the channels, the mechanism of ion permeation is
      unknown. Here we used a method proposed in an accompanying paper (Cheng and
      Zhorov in Eur Biophys J, 2009) to predict possible chelation patterns of calcium
      ions in a structural model of the L-type calcium channel. We compared three
      models in which two or three calcium ions interact with the four selectivity
      filter glutamates and a conserved aspartate adjacent to the glutamate in repeat
      II. Monte Carlo energy minimizations yielded many complexes with calcium ions
      bound to at least two selectivity filter carboxylates. In these complexes calcium
      carboxylate attractions are counterbalanced by calcium-calcium and carboxylate
      carboxylate repulsions. Superposition of the complexes suggests a high degree of
      mobility of calcium ions and carboxylate groups of the glutamates. We used the
      predicted complexes to propose a permeation mechanism that involves single-file
      movement of calcium ions. The key feature of this mechanism is the presence of
      bridging glutamates that coordinate two calcium ions and enable their transitions
      between different chelating patterns involving four to six oxygen atoms from the
      channel protein. The conserved aspartate is proposed to coordinate a calcium ion
      incoming to the selectivity filter from the extracellular side. Glutamates in
      repeats III and IV, which are most distant from the repeat II aspartate, are
      proposed to coordinate the calcium ion that leaves the selectivity filter to the
      inner pore. Published experimental data and earlier proposed permeation models
      are discussed in view of our model.

PMID- 20054688
TI  - Targeting MARCO can lead to enhanced dendritic cell motility and anti-melanoma
      activity.
AB  - We reported that murine tumor lysate-pulsed dendritic cells (TP-DC) could elicit
      tumor-specific CD4(+) and CD8(+) T cells in vitro and in vivo. In some limited
      cases, TP-DC treatments in vivo could also result in regression of established
      subcutaneous tumors and lung metastases. By gene array analysis, we reported a
      high level of expression of a novel member of the cell surface class A scavenger
      receptor family, MARCO, by murine TP-DC compared to unpulsed DC. MARCO is thought
      to play an important role in the immune response by mediating binding and
      phagocytosis, but also in the formation of lamellipodia-like structures and
      dendritic processes. We have now examined the biologic and therapeutic
      implications of MARCO expressed by TP-DC. In vitro exposure of TP-DC to a
      monoclonal anti-MARCO antibody resulted in a morphologic change of rounding with
      disappearance of dendritic-like processes. TP-DC remained viable after anti-MARCO
      antibody treatment; had little, if any, change in production of IL-10, IL-12p70
      and TNF-alpha; but demonstrated enhanced migratory capacity in a microchemotaxis
      assay. The use of a selective inhibitor showed MARCO expression to be linked to
      the p38 mitogen-activated protein kinase (MAPK) pathway. In vivo, anti-MARCO
      antibody treated TP-DC showed better trafficking from the skin injection site to
      lymph node, enhanced generation of tumor-reactive IFN-gamma producing T cells,
      and improved therapeutic efficacy against B16 melanoma. These results, coupled
      with our finding that human monocyte-derived DC also express MARCO, could have
      important implications to human clinical DC vaccine trials.

PMID- 20054691
TI  - Transient involvement of the cerebral cortex in a flare of Behcet's syndrome.
AB  - We describe a flare of Behcet's syndrome in a 42-year-old man who presented with
      florid mucocutaneous manifestations, headache and vomiting, but without meningeal
      or neurologic signs. A single, non-enhancing cortical lesion was found in the
      frontal lobe by computed tomography and magnetic resonance (MR) imaging studies.
      Diffusion-weighted analysis and MR spectroscopy were consistent with focal
      inflammation. The patient improved with colchicine, and after 5 months, a repeat
      MR scan demonstrated resolution of the inflammatory changes suggesting that
      involvement of the cerebral cortex may be a self-limiting phenomenon, distinct
      from other more frequent and destructive parenchymal manifestations of neuro
      Behcet's disease.

PMID- 20054692
TI  - Genetic polymorphism of PITX1 in susceptibility to knee osteoarthritis in a
      Chinese Han population: a case-control study.
AB  - Osteoarthritis (OA) is the most common form of arthritis and the precise etiology
      of this disease remains unclear. Genetic factors play a considerable role in
      pathogenesis of OA. Several OA-susceptibility genes have been identified.
      Recently, a new emerging role of pitx1 transcription factor in OA pathogenesis
      has been reported. Paired-like homeodomain transcription factor 1 (PITX1) has
      been implicated in hind limb development of mice and is essential to maintain
      cartilage function. Because of the different expression in the knee joint between
      OA and normal people, PITX1 may be involved in etiology and pathogenesis of OA.
      The present study is to evaluate the association of the PITX1 polymorphism
      (rs479632) with knee OA in a Chinese Han population. A case-control association
      study was conducted. The polymorphism was genotyped in 581 patients who had
      primary symptomatic knee OA with radiographic confirmation and in 570 matched
      controls. Allelic and genotypic frequencies were compared between patients and
      control subjects. No significant difference was detected in genotype or allele
      distribution between knee OA and control groups (all P > 0.05). The association
      was also negative even after stratification by sex. Furthermore, no association
      between the SNP genotype and the clinical variables age, sex, body mass index
      (BMI), and Kellgren/Lawrence (K/L) score was observed in OA patients. The present
      study suggests that the PITX1 polymorphism (rs479632) is not a risk factor for
      knee OA susceptibility in the Chinese Han population. Further studies are needed
      to give a global view of this polymorphism in pathogenesis of OA.

PMID- 20054693
TI  - Longitudinal growth attainments of Indian boys with juvenile rheumatoid
      arthritis.
AB  - The objective is to study the pattern of distance and velocity growth in terms of
      weight and height in adolescent boys with Juvenile Rheumatoid Arthritis (JRA).
      This study was conducted on children diagnosed to have JRA (Cassidy and Petty in
      Juvenile Rheumatoid Arthritis, WB Saunders Co., Philadelphia, 2005) at the
      Pediatric Rheumatology and Immunology Clinic of Advanced Pediatrics Centre, Post
      Graduate Institute of Medical Education and Research, Chandigarh. A total of 203
      observations made on 70 boys with JRA, between 9 and 17 years of age, comprised
      the sample for this prospective mixed-longitudinal growth study. Each subject was
      measured for body weight and standing height using standardized anthropometric
      techniques (Eveleth and Tanner in Worldwide variation in human growth, Cambridge
      University Press, New York, 1990) at half yearly age intervals. All
      anthropometric measurements were carried out in the Growth Laboratory of Advanced
      Pediatrics Centre. Boys with polyarticular and systemic onset types of JRA in
      general measured lighter than their pauciarticular counterparts throughout the
      period of study. Height attainments in boys with polyarticular and systemic onset
      JRA measured shorter than their pauciarticular counterparts till 15 years and 12
      years, respectively, where-after they became comparable to boys with
      pauciarticular JRA. As compared to normal Indian (Bhalla and Kumar in Int J
      Anthropol 18:113-125, 2003; Aggarwal et al. in Indian Pediatr 29:1203-1282, 1992)
      and American (Ogden et al. in Pediatrics 109:45-60, 2002) counterparts boys
      representing all categories of JRA remained lighter and shorter. Onset of Peak
      Height Velocity (PHV) in boys with polyarticular JRA (i.e. 12.5 years) was
      delayed by 1 year as compared to boys with pauciarticular JRA (i.e. 11.5 years).
      Attainment of Peak Weight Velocity (PWV) in boys with polyarticular JRA (i.e.
      13.5 years) was also delayed by 1 year when compared to those with pauciarticular
      type (i.e. 12.5 years). In conclusion, weight and height growth attainments in
      Indian adolescent boys afflicted with different categories of JRA in general
      remained impaired as compared to their normal counterparts. However, the
      magnitude of growth deficit experienced by them appears to be a disease severity
      related phenomenon. This is the first study of its kind from a developing
      country.

PMID- 20054694
TI  - Association of coronary artery calcium and congestive heart failure in the
      general population: Results of the Heinz Nixdorf Recall study.
AB  - BACKGROUND: The main causes of congestive heart failure (CHF) are coronary artery
      disease (CAD) and arterial hypertension. Coronary artery calcification (CAC)
      evidencing coronary atherosclerosis may occur prior to clinical CAD. The aim of
      our study was to assess the association between CAC as a sign of subclinical CAD
      and CHF in a general unselected population. METHODS: Participants of the Heinz
      Nixdorf Recall Study without known CAD but with known CHF as defined by a
      physicians' diagnosis of CHF and dyspnea were identified. B-natriuretic peptide
      was measured and an exercise stress test was performed as possible.
      Cardiovascular risk factors and the EBCT-based CAC Agatston score were
      determined. RESULTS: Those 105/4,230 subjects (2.5%) with CHF (age 65 +/- 7
      years, 44% males), had higher brain natriuretic peptide (BNP) levels (median BNP
      36.8 [16.5-70.1] vs. 17.6 [9.5-31.7] pg/ml, p<0.01) and lower exercise capacity
      (108.7 +/- 39.4 vs. 130.0 +/- 40.7 W, p<0.01) than those without. CAC in subjects
      with CHF was significantly higher than in those without (median CAC 64.7 [8.5
      312.3] vs. 11.6 [0-109.8], p<0.01). In univariate analysis, CAC-burden after
      logarithmic transformation according to log(2)(CAC + 1) showed a significant
      association with the presence of CHF (odds ratio (OR) (95% CI): 1.16 (1.1-1.23),
      p<0.0001). Adjustment for age and sex (OR 1.11 (1.04-1.18), p<0.001), additional
      Framingham risk score (OR 1.09 (1.02-1.16), p = 0.015), and additional
      cardiovascular medication (OR 1.07 (0.998-1.14), p = 0.058) attenuated this
      association. Age, systolic blood pressure, antihypertensive medication and
      increased body mass index also remained significantly associated with presence of
      CHF in the full multivariate model. CONCLUSION: The observed association between
      CAC and CHF in persons without clinically overt CAD is partly determined by risk
      factors that are involved in the natural history of both CAC and CHF. Whether CAC
      has a role to identify subjects at risk of future CHF remains to be determined
      using follow-up analyses.

PMID- 20054695
TI  - Medial vestibulospinal tract lesions impair sacculo-collic reflexes.
AB  - The medial vestibulospinal tract (VST) is known to mediate the vestibular-evoked
      myogenic potential (VEMP) in the contracting sternocleidomastoid muscle (SCM). To
      determine whether disruption of the medial VST in the medulla impairs formation
      of VEMP, we measured VEMP in 14 patients with medial medullary infarction (MMI).
      VEMP was induced by a short tone burst and was recorded in contracting SCM while
      patients turned their heads forcefully to the contralateral side against
      resistance. Normative data were obtained from 47 healthy volunteers. Seven
      patients (50%) had abnormal VEMP in the side of the MMI lesion, absent in two,
      decreased in four, and delayed in two. One patient showed both decreased and
      delayed response. Of the seven patients with abnormal VEMP, five had the lesions
      that extended to the dorsal tegmentum while five of the seven patients with
      normal VEMP showed restricted anteromedial lesions mainly involving the pyramids.
      Spontaneous nystagmus (4/7, 57%), gaze-evoked nystagmus (6/7, 86%), and ocular
      tilt reaction/tilt of the subjective visual vertical (4/7, 57%) were frequently
      observed in the patients with abnormal VEMP. The abnormal VEMP in patients with
      infarctions involving the medullary tegmentum supports that VEMP is mediated by
      the medial VST descending within the medial longitudinal fasciculus.

PMID- 20054690
TI  - Life in the midst of scarcity: adaptations to nutrient availability in
      Saccharomyces cerevisiae.
AB  - Cells of all living organisms contain complex signal transduction networks to
      ensure that a wide range of physiological properties are properly adapted to the
      environmental conditions. The fundamental concepts and individual building blocks
      of these signalling networks are generally well-conserved from yeast to man; yet,
      the central role that growth factors and hormones play in the regulation of
      signalling cascades in higher eukaryotes is executed by nutrients in yeast.
      Several nutrient-controlled pathways, which regulate cell growth and
      proliferation, metabolism and stress resistance, have been defined in yeast.
      These pathways are integrated into a signalling network, which ensures that yeast
      cells enter a quiescent, resting phase (G0) to survive periods of nutrient
      scarceness and that they rapidly resume growth and cell proliferation when
      nutrient conditions become favourable again. A series of well-conserved nutrient
      sensory protein kinases perform key roles in this signalling network: i.e. Snf1,
      PKA, Tor1 and Tor2, Sch9 and Pho85-Pho80. In this review, we provide a
      comprehensive overview on the current understanding of the signalling processes
      mediated via these kinases with a particular focus on how these individual
      pathways converge to signalling networks that ultimately ensure the dynamic
      translation of extracellular nutrient signals into appropriate physiological
      responses.

PMID- 20054696
TI  - Switch costs and the operand-recognition paradigm.
AB  - Experimental research in cognitive arithmetic frequently relies on participants'
      self-reports to discriminate solutions based on direct memory retrieval from use
      of procedural strategies. Given concerns about the validity and reliability of
      strategy reports, Thevenot et al. in Mem Cogn 35:1344-1352, (2007) developed the
      operand-recognition paradigm as an objective measure of arithmetic strategies.
      Participants performed addition or number comparison on two sequentially
      presented operands followed by a speeded operand-recognition task. Recognition
      times increased with problem size following addition but not comparison. Thevenot
      et al. argued that the complexity of addition strategies increases with problem
      size. A corresponding increase in operand-recognition time occurs because, as
      problem size increases, working memory contains more numerical distracters.
      However, because addition is substantially more difficult than comparison, and
      difficulty increases with problem size for addition but not comparison, their
      findings could be due to difficulty-related task-switching costs. We repeated
      Thevenot et al. (Experiment 1) but added a control condition wherein participants
      performed a parity (odd or even) task instead of operand recognition. We
      replicated their findings for operand recognition but found robust, albeit
      smaller, effects of addition problem size on parity judgements. The results
      indicate that effects of strategy complexity in the operand-recognition paradigm
      are confounded with task-switching effects, which complicates its application as
      a precise measure of strategy complexity in arithmetic.

PMID- 20054697
TI  - Mediator subunits and histone methyltransferase Set2 contribute  to Ino2
      dependent transcriptional activation of phospholipid  biosynthesis in the yeast
      Saccharomyces cerevisiae.
AB  - To activate eukaryotic genes, several pathways which modify chromatin and recruit
      general factors of the transcriptional machinery are utilized. We investigated
      the factors required for activation of yeast phospholipid biosynthetic genes,
      depending on activator protein Ino2 which binds to the inositol/choline
      responsive element (ICRE) upstream promoter motif together with its partner
      protein Ino4. We used a set of 15 strains each defective for one of the non
      essential subunits of yeast mediator complex and identified med2, med3, med15,
      med18 and med19 as impaired for inositol biosynthesis. In these mutants, ICRE
      dependent gene activation was reduced to 13-22% of the wild-type level. We also
      demonstrate synthetic growth and activation defects among mediator mutants and
      mutants lacking defined histone modifications (snf1, gcn5) and transcriptional
      coactivators (sub1). Analysis of mutants defective for histone methylation (set1,
      set2 and dot1) and demethylation (jhd1, jhd2, gis1, rph1 and ecm5) revealed the
      importance of the H3 Lys36-specific Set2 methyltransferase for ICRE-dependent
      gene expression. Although defined mediator subunits are critical for gene
      activation, we could not detect their interaction with Ino2. In contrast, Ino2
      directly binds to the Set2 histone methyltransferase. Mapping of interaction
      domains revealed the importance of the SET core domain which was necessary and
      sufficient for binding Ino2.

PMID- 20054698
TI  - Chronic hepatitis C increased the mortality rates of patients with hepatocellular
      carcinoma and diabetes mellitus in a triple hepatitis virus endemic community.
AB  - BACKGROUND: To elucidate the factors associated with mortality rates among older
      subjects with hepatocellular carcinoma (HCC) and diabetes mellitus (DM) in a
      triple hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis delta virus
      (HDV) endemic community. METHODS: A total of 2,909 residents aged>or=45 years
      were screened for hepatitis B surface antigen (HBsAg), antibodies to HCV (anti
      HCV) and alanine aminotransaminase (ALT) in 1997. Anti-HDV was detected in HBsAg
      positive subjects. Those who expired from HCC and DM were identified from
      official mortality data sets (1997-2003). Survival was analyzed using the Kaplan
      Meier survival curve with log-rank test and the Cox proportional hazard model.
      RESULTS: Forty-one patients died of HCC and 25 of DM during the study period.
      Multivariate analysis indicated that age>or=65 years (hazard ratio 3.4; 95%
      confidence interval 1.8-6.4), HBsAg (3.3; 1.7-6.7), anti-HCV (3.8; 1.7-8.5) and
      ALT>or=40 IU/L (3.7; 1.9-7.0) were independent predictors of HCC mortality, while
      age>or=65 years (4.8; 2.1-11.0) and anti-HCV (4.2; 1.7-10.6) were two independent
      predictors of DM mortality. There were synergistic effects of dual viral
      infections for HCC, but not for DM mortality. CONCLUSIONS: Old age and chronic
      HCV infection increase the risk of HCC and DM mortality. HBsAg and ALT levels are
      also risk factors for HCC mortality, but not DM. The synergistic effects of dual
      hepatitis viral infections are demonstrable and warrant further investigation.

PMID- 20054699
TI  - Operative intervention for delayed symptomatic radionecrotic masses developing
      following stereotactic radiosurgery for cerebral arteriovenous malformations-
      case analysis and literature review.
AB  - CASE REPORT: We report two cases of operative intervention that was beneficial in
      the treatment of delayed symptomatic radionecrotic masses that had developed
      following stereotactic radiosurgery (SRS) using the gamma knife (GK) for the
      treatment of cerebral arteriovenous malformations (AVM). DISCUSSION: Case 1
      involved a small craniotomy for decompression of a large cerebral multiloculated
      cyst, which had become symptomatic 84 months following gamma knife treatment for
      a left frontal lobe AVM. Case 2 involved surgical excision of an occipital
      radionecrotic mass 72 months following GK treatment for an occipital AVM. This
      patient had suffered from longstanding symptomatic cerebral oedema, which on
      occasions had become life threatening. Case 2 is also the first report of a
      radionecrotic mass occurring post-SRS for an AVM, which conversely appeared to
      demonstrate increased uptake on single photon emission computed tomography
      (SPECT) scan. The first literature review of such delayed symptomatic
      radionecrotic lesions is presented. There appears to be a late onset of symptoms
      (average 55 months, range 12-111 months) associated with such radionecrosis.
      Drainage of such cysts or excision of the mass lesion appears to be consistently
      beneficial to the patients and appears to be uncomplicated. CONCLUSION: We
      recommend early surgical intervention for such delayed symptomatic radionecrotic
      masses that do not resolve following non-operative management. We also recommend
      caution in interpretation of SPECT scan results when attempting to differentiate
      radionecrosis from neoplasia.

PMID- 20054700
TI  - Mycophenolate mofetil in Takayasu's arteritis.
AB  - Mycophenolate mofetil (MMf) has recently been reported as a useful alternative
      immunosuppressive drug in autoimmune diseases. There is paucity of literature on
      its use in Takayasu's arteritis (TA). The aim of this study was to assess the
      safety and efficacy of MMf in Asian Indian patients with Takayasu's arteritis.
      Records of 21 consecutive patients with TA on treatment with oral MMF attending
      our centre from January 2005 to August 2008 were studied. The clinical,
      laboratory and angiography findings were noted and disease activity assessment
      was done using Indian Takayasu's arteritis activity score (ITAS) and physician's
      global observation score at baseline and last follow-up. Eleven patients were on
      steroids alone at baseline while ten patients had received azathioprine prior to
      administration of mycophenolate. The mean duration of follow-up on mycophenolate
      was 9.6 (+/-6.4) months. Nineteen patients (90%) received mycophenolate due to
      active disease, while in the other two patients, it was given to facilitate
      steroid tapering. Mycophenolate had to be discontinued in one patient due to skin
      rash. At the last visit, all the remaining 20 patients who continued
      mycophenolate had improvement in disease activity as evident by the drop in
      median ITAS [7 (range 0-19) versus 1 (range 0-7); p=0.001]. A similar trend was
      noted in laboratory markers of inflammation with a reduction in mean Erythrocyte
      Sedimentation Rate (ESR) (68+/-36.5 versus 43.2+/-34 mm/first hour; p=0.003) and
      mean C - Reactive protein (CRP) (31+/-46.7 versus 17.3+/-23.9 mg/L; p=1.00). All
      patients received concomitant steroids, but there was a significant decrease in
      steroid dosage from 36 (+/-16) mg/day at baseline to 19 (+/-14) mg/day at last
      follow-up (p<0.001). This study is the largest series till date establishing the
      use of mycophenolate as a safe and effective steroid-sparing immunosuppressant in
      Takayasu's arteritis.

PMID- 20054701
TI  - Annular erythema associated with Sjogren's syndrome: review of the literature on
      the management and clinical analysis of skin lesions.
AB  - Annular erythema has been recognized to be a specific, cutaneous manifestation
      associated with Sjogren's syndrome. Based on a search of the literature up to
      2007, annular erythema with Sjogren's syndrome (AESS) preferentially occurs in
      Asian but not in Western populations. However, the precise clinical course and
      standard regimen for the management of AESS have remained obscure, primarily
      because of its rare occurrence in Western populations and the fact that most
      Asian cases are isolated reports. In this study, 28 cases of AESS from our
      department and 92 cases distilled from the literature were enrolled in a
      retrospective study to evaluate the clinical characteristics and most desirable
      management of this skin manifestation in Sjogren's syndrome. We found that 75% of
      all cases with AESS were positive for both anti-SSA and anti-SSB antibodies.
      Multiple therapeutic options are available to treat AESS, including oral
      steroids. Several anti-malaria drugs or tacrolimus ointment have also been
      reported to be effective against AESS. AESS is a distinct clinical entity, and a
      small dose of prednisolone (approx. 10 mg) is sufficient to control diseases
      activity, except in some cases with systemic manifestations, and this treatment
      has a more rapid clinical effect than topical steroids.

PMID- 20054702
TI  - A case with coincidental diagnosis of primary central nervous system lymphoma and
      lymph node sarcoidosis.
AB  - Primary central nervous system lymphoma (PCNSL) is rare. Clinical and
      histological differential diagnosis of systemic lymphoma and sarcoidosis
      continues to be a challenge. The first case report in the German and English
      literature of PCNSL and synchronous sarcoidosis is presented. Synchronous
      mediastinal lymphadenopathy suggestive of non-Hodgkin's lymphoma (NHL) or
      sarcoidosis was noted. Both conditions require alternative therapeutic and
      prognostic considerations to PCNSL. A regime of intrathecal and adjuvant systemic
      chemotherapy led to transient clinical improvement prior to the patient's demise
      through overwhelming sepsis and multiorgan failure. Post mortem findings
      confirmed synchronous PCNSL with mediastinal lymph node sarcoidosis.

PMID- 20054703
TI  - Spatial distribution of lead concentrations in urban surface soils of New
      Orleans, Louisiana USA.
AB  - Immediately following hurricane Katrina concern was raised over the environmental
      impact of floodwaters on the city of New Orleans, especially in regard to human
      health. Several studies were conducted to determine the actual contaminant
      distribution throughout the city and surrounding wetlands by analyzing soil,
      sediment, and water for a variety of contaminants including organics, inorganics,
      and biologics. Preliminary investigations by The Institute of Environmental and
      Human Health at Texas Tech University concluded that soils and sediments
      contained pesticides, semi-volatiles, and metals, specifically arsenic, iron, and
      lead, at concentrations that could pose a significant risk to human health.
      Additional studies on New Orleans floodwaters revealed similar constituents as
      well as compounds commonly found in gasoline. More recently, it has been revealed
      that lead (Pb), arsenic, and vanadium are found intermittently throughout the
      city at concentrations greater than the human health soil screening levels
      (HHSSLs) of 400, 22 (non-cancer endpoint) and 390 MUg/g, respectively. Of these,
      Pb appears to present the greatest exposure hazard to humans as a result of its
      extensive distribution in city soils. In this study, we spatially evaluated Pb
      concentrations across greater New Orleans surface soils. We established 128
      sampling sites throughout New Orleans at approximately half-mile intervals. A
      soil sample was collected at each site and analyzed for Pb by ICP-AES. Soils from
      19 (15%) of the sites had Pb concentrations exceeding the HHSSL threshold of 400
      MUg/g. It was determined that the highest concentrations of Pb were found in the
      south and west portions of the city. Pb concentrations found throughout New
      Orleans in this study were then incorporated into a geographic information system
      to create a spatial distribution model that can be further used to predict Pb
      exposure to humans in the city.

PMID- 20054705
TI  - Toxicological study and efficacy of blank and paclitaxel-loaded lipid
      nanocapsules after i.v. administration in mice.
AB  - PURPOSE: Lipid nanocapsules (LNCs) are solvent-free drug nanocarriers permitting
      entrapment of paclitaxel and increasing its antitumoural effect in animal models
      after i.v. injection. The tolerance and efficacy of LNCs after repeated dose i.v.
      administration were assessed in mice. The maximum tolerated dose (MTD) and 50
      percent lethal dose (LD50) were studied. METHODS: Paclitaxel-loaded LNC
      formulation was given i.v. at the dose of 12 mg/kg per day for 5 consecutive days
      in comparison with blank LNCs and saline. Histological examination, complete
      blood counts and biochemical quantification were performed after a recovery of 7
      days. Growth of NCI-H460 subcutaneous xenografts in nude mice receiving one of
      the aforementioned schedules was assessed. MTD and LD50 were determined by Irwin
      test. RESULTS: No mortality was observed in repeated injections studies.
      Histological studies revealed no lesions and no accumulation of lipids. Blood
      studies were normal. The tumoural growth was significantly reduced in the group
      treated by paclitaxel-loaded LNCs. The MTDs/LD50s of Taxol, paclitaxel-loaded
      LNCs and blank LNCs were 12/19.5, 96/216 and above 288/288 mg/kg, respectively.
      CONCLUSIONS: This study demonstrates that a five-day i.v. injection schedule of
      paclitaxel-loaded LNC dispersions induces no histological or biochemical
      abnormalities in mice and improves paclitaxel efficacy and therapeutic index in
      comparison with Taxol.

PMID- 20054706
TI  - Enantioselective fluorescent sensors for amino acid derivatives based on BINOL
      bearing S-tryptophan unit: synthesis and chiral recognition.
AB  - Four novel derivatives of BINOL bearing S-tryptophan unit have been prepared and
      the structures of these compounds characterized by IR, MS, (1)H and (13)C NMR
      spectroscopy and elemental analysis. The enantioselective recognition of these
      receptors has been studied by fluorescence titration and (1)H NMR spectroscopy.
      The receptors exhibited different chiral recognition abilities towards N-Boc
      protected amino acid anions and formed 1:1 complexes between host and guest.
      Receptors exhibit excellent enantioselective fluorescent recognition ability
      towards the amino acid derivatives.

PMID- 20054707
TI  - A cross-cultural comparison of hospice development in Japan, South Korea, and
      Taiwan.
AB  - By 2050, one out of four people in Eastern Asia will be aged 65 and above. Thus,
      preparing to care for an older population is imperative. Addressing quality care
      for elders includes consideration of palliative and end-of-life care. A
      comparative study of the development of hospice and palliative care services in
      Japan, South Korea, and Taiwan, is presented, based on an extensive literature
      review. Both commonalities and differences were found. This article provides
      information on the origins and administration of hospice services in these three
      cases, as well as the degree of government involvement. Cultural and religious
      aspects are also considered, and obstacles to the spread of hospice services are
      discussed. This review compares experiences with hospice services and identifies
      factors that influence people's perceptions and adoption of hospice. Stronger
      financial support for hospice and palliative care through the government and
      insurance programs would help increase the availability and use of services.
      Also, the need for continuing education of healthcare providers, patients,
      families, and the community is urgent. However, promotion of understanding of
      better pain management and the worth of hospice and palliative care must be
      conducted in ways that are sensitive to the cultural values and traditions in
      Japan, South Korea, and Taiwan. Only when hospice and palliative care can be
      viewed as an admirable choice for one's loved ones, overcoming issues of truth
      telling, filial piety, worries about how one is judged, and religious
      considerations, will it become more widely accepted.

PMID- 20054708
TI  - Parkinson's disease and cancer risk: a systematic review and meta-analysis.
AB  - OBJECTIVE: To appraise the existing literature on cancer risk among patients with
      Parkinson's disease (PD), determine the overall cancer risk ratio among patients
      with PD, explore reasons for variations in study results, and assess the
      potential for publication bias. METHODS: Studies reporting cancer risk in
      patients with PD were identified by searching electronic databases through 18
      November 2009 using the terms PARKINSON DISEASE, NEOPLASM, and CANCER. Reviewers
      individually performed data extraction and scored each study using a quality
      assessment instrument. Cancer risk in all patients with PD was calculated
      overall, and after excluding melanoma and other skin cancers. We tested for
      heterogeneity and publication bias, and stratified for gender, smoking-related
      versus non-smoking-related cancers, and study quality. We pooled effect sizes
      using fixed-effects and random-effects models. RESULTS: We included 29 studies in
      the overall analysis for a total of 107,598 patients with PD. Compared to
      controls, the aggregate risk for cancer in patients with PD was 0.73 (95%
      confidence interval [CI], 0.63-0.83), and after excluding skin tumors, 0.69 (95%
      CI, 0.62-0.78). These risks varied by gender (males, RR = 0.71, 95% CI, 0.57
      0.88; females, RR = 0.82; 95% CI, 0.68-0.98). After strictly excluding skin
      tumors, both smoking-related (RR = 0.61; 95% CI, 0.58-0.65) and non-smoking
      related cancer rates (RR = 0.76; 95% CI, 0.65-0.89) were significantly lower
      among patients with PD . CONCLUSIONS: Studies on cancer risk among patients with
      PD collectively show significantly reduced cancer risk ratios. Further research
      to explain the biological mechanisms, particularly for the association with non
      smoking-related cancers, appears warranted.

PMID- 20054709
TI  - Birth weight, breast cancer susceptibility loci, and breast cancer risk.
AB  - BACKGROUND: There is considerable evidence that birth weight is positively
      associated with breast cancer risk, and seven single-nucleotide polymorphisms
      (SNPs) have been conclusively associated with this risk. We have hypothesized
      that breast cancer susceptibility loci may have a greater influence on breast
      cancer risk among women with higher birth weight, who are expected to have a
      larger pool of mammary stem cells that are susceptible to malignant
      transformation. PATIENTS AND METHODS: In the context of a nationwide, population
      based case-control study in Sweden, we retrieved recorded birth weight for 693
      breast cancer cases and 747 control women who were also genotyped for most or all
      of the seven recently documented breast cancer susceptibility SNPs: rs2981582,
      rs12443621, rs8051542, rs3803662, rs889312, rs13281615, and rs3817198. RESULTS:
      We grouped heterozygotes with homozygotes for the wild-type allele, and we found
      a marginally significant interaction (p~0.07) between birth weight and rs2981582
      (FGFR2), the genotype repeatedly identified as the top hit in genome-wide
      association studies. There were similar, though not significant, patterns for the
      other six SNPs. CONCLUSIONS: Although our findings require confirmation, we found
      suggestive evidence that genetic susceptibility modifies the positive association
      of birth weight with breast cancer.

PMID- 20054710
TI  - Assessment of toxic heavy metals in urban lake sediments as related to urban
      stressor and bioavailability.
AB  - A suite of heavy metals was monitored at sediments and overlying water in three
      urban lakes located in Seoul, Korea during spring season 2006. Metals measured
      were zinc, arsenic, chromium, copper, nickel, and cadmium. All metal
      concentrations in urban lake sediments were much higher than those in natural
      lake sediments. Elevated metal levels in urban lake sediments are associated with
      urban runoff, including street dust polluted by heavy metals. Metals in sediments
      from urban lakes were extracted with a weak electrolyte solution (0.1 M
      Ca(NO(3))(2)) to predict the toxicity of metals. Among the six heavy metals
      studied, Cu was the most extractable, followed by Ni and Zn. Ca(NO(3))(2)
      extractable metal recoveries has a good relationship with metal toxicity based on
      Chironomus riparius bioassay. This study showed that urban stressors such as
      vehicle emissions could increase the concentration of heavy metals in urban lake
      sediments. In addition, there is a positive relationship between sediment
      toxicity by using C. riparius bioassay and Ca(NO(3))(2)-extractability of heavy
      metals from sediments.

PMID- 20054711
TI  - A qualitative analysis of the regulation of cyclic electron flow around
      photosystem I from the post-illumination chlorophyll fluorescence transient in
      Arabidopsis: a new platform for the in vivo investigation of the chloroplast
      redox state.
AB  - A transient in chlorophyll fluorescence after cessation of actinic light
      illumination, which has been ascribed to electron donation from stromal
      reductants to plastoquinone (PQ) by the NAD(P)H-dehydrogenase (NDH) complex, was
      investigated in Arabidopsis thaliana. The transient was absent in air in a mutant
      lacking the NDH complex (ndhM). However, in ndhM, the transient was detected in
      CO(2)-free air containing 2% O(2). To investigate the reason, ndhM was crossed
      with a pgr5 mutant impaired in ferredoxin (Fd)-dependent electron donation from
      NADPH to PQ, which is known to be redundant for NDH-dependent PQ reduction in the
      cyclic electron flow around photosystem I (PSI). In ndhM pgr5, the transient was
      absent even in CO(2)-free air with 2% O(2), demonstrating that the post
      illumination transient can also be induced by the Fd- (or PGR5)-dependent PQ
      reduction. On the other hand, the transient increase in chlorophyll fluorescence
      was found to be enhanced in normal air in a mutant impaired in plastid fructose
      1,6-bisphosphate aldolase (FBA) activity. The mutant, termed fba3-1, offers
      unique opportunities to examine the relative contribution of the two paths, i.e.,
      the NDH- and Fd- (or PGR5)-dependent paths, on the PSI cyclic electron flow.
      Crossing fba3-1 with either ndhM or pgr5 and assessing the transient suggested
      that the main route for the PSI cyclic electron flow shifts from the NDH
      dependent path to the Fd-dependent path in response to sink limitation of linear
      electron flow.

PMID- 20054712
TI  - Enrichment of oxygen heavy isotopes during photosynthesis in phytoplankton.
AB  - Some of the oxygen produced during oxygenic photosynthesis is consumed but little
      is known about the extent of the processes involved. We measured the (17)O/(16)O
      and (18)O/(16)O ratios in O(2) produced by certain marine and freshwater
      phytoplankton representing important groups of primary producers. When the cells
      were performing photosynthesis under very low dissolved oxygen concentrations (<
      3 MUM), we observed significant enrichment in both (18)O and (17)O with respect
      to the substrate water. The difference in delta(18)O between O(2) and water was
      about 4.5, 3, 5.5, and 70/000 in the diatom Phaeodactylum tricornutum,
      Nannochloropsis sp. (Eustigmatophyceae), the coccolithophore Emiliania huxleyi
      and the green alga Chlamydomonas reinhardtii, respectively. The difference in
      delta(17)O was about 0.52 that of delta(18)O. As explained, the observed
      enrichments most probably stem from considerable oxygen consumption during
      photosynthesis even when major O(2)-consuming reactions such as photorespiration
      were minimized. These enrichments increased linearly with rising O(2) levels but
      with different delta(17)O/delta(18)O slopes for the various organisms, suggesting
      engagements of different O(2)-consuming reactions with rising O(2) levels.
      Consumption of O(2) may be important for energy dissipation during
      photosynthesis. The isotope enrichment observed here, not accounted for in
      earlier assessments, closes an important gap in our understanding of the
      difference between the isotopic compositions of atmospheric oxygen and that of
      seawater, i.e., the Dole effect.

PMID- 20054713
TI  - Assessing the left atrial phasic volume and function  with dual-source CT:
      comparison with 3T MRI.
AB  - We wanted to assess the performance of dual-source CT (DSCT) for evaluating the
      left atrial volume and function and we compared this performance to that of the
      standard reference technique,cardiac cine MR (CMR). Fifty-one patients who were
      referred for CT coronary angiography were included in the study. Two were
      subsequently excluded for having un-analyzable MR images at the onset of left
      atrial contraction. For the remaining 49 patients, the DSCT data sets and FIESTA
      (fast imaging employing steady-state acquisition) cines of the vertical long axis
      covering the left atrium and the short axis covering the left ventricle were
      obtained on the same day. All the images were analyzed to obtain the maximal left
      atrial volume (LAVmax), the minimal left atrial volume (LAVmin), the left atrial
      volume just before left atrium contraction (LAVp), the left atrial reservoir
      volume (LARV), the left atrial ejection fraction (LAEF), the left atrial passive
      emptying volume (LAPV), the left atrial active emptying volume(LAAV), the left
      atrial conduit volume (LACV), the left ventricular end-diastolic volume (LVEDV),
      the left ventricular end-systolic volume (LVESV) and the left ventricular stroke
      volume (LVSV) by using 3D semi-segmentation software and Report Card 2.0
      software, respectively, for the DSCT and CMR. All the parameters were normalized
      to the body surface area. Intermodality agreement was tested through linear
      regression and Bland-Altman analyses.Repeated measurements were performed to
      determine the interobserver variability. The DSCT measurements resulted in good
      correlation (r > 0.75) compared with those of CMR. However, DSCT slightly,but
      insignificantly overestimated the indexed LAVmax, LAVmin, LAVp, LARV, LAPV, LAAV
      and LACV, as reflected by biases of 1.2, 0.9, 1.1, 0.3, 0.1,0.2 and 0.4 ml/m(2),
      respectively. The LAEF was minimally, but insignificantly underestimated as
      reflected by a bias of -0.6% (P = ns). The variability of the DSCT measurements
      was lower than that of the CMR values. DSCT provides highly reliable and
      reproducible measurements of the left atrial phasic volume and function in
      patients who are referred for coronary CT imaging.

PMID- 20054714
TI  - Backward bifurcation and optimal control in transmission dynamics of west nile
      virus.
AB  - The paper considers a deterministic model for the transmission dynamics of West
      Nile virus (WNV) in the mosquito-bird-human zoonotic cycle. The model, which
      incorporates density-dependent contact rates between the mosquito population and
      the hosts (birds and humans), is rigorously analyzed using dynamical systems
      techniques and theories. These analyses reveal the existence of the phenomenon of
      backward bifurcation (where the stable disease-free equilibrium of the model co
      exists with a stable endemic equilibrium when the reproduction number of the
      disease is less than unity) in WNV transmission dynamics. The epidemiological
      consequence of backward bifurcation is that the classical requirement of having
      the reproduction number less than unity, while necessary, is no longer sufficient
      for WNV elimination from the population. It is further shown that the model with
      constant contact rates can also exhibit this phenomenon if the WNV-induced
      mortality in the avian population is high enough. The model is extended to assess
      the impact of some anti-WNV control measures, by re-formulating the model as an
      optimal control problem with density-dependent demographic parameters. This
      entails the use of two control functions, one for mosquito-reduction strategies
      and the other for personal (human) protection, and redefining the demographic
      parameters as density-dependent rates. Appropriate optimal control methods are
      used to characterize the optimal levels of the two controls. Numerical
      simulations of the optimal control problem, using a set of reasonable parameter
      values, suggest that mosquito reduction controls should be emphasized ahead of
      personal protection measures.

PMID- 20054715
TI  - Breast contouring in postbariatric patients: a technique selection algorithm.
AB  - BACKGROUND: Breast deformities in postbariatric surgery (post-BS) patients are
      different and more challenging than those from non-BS patients. The histological
      alterations confer the highest clinical consequences to this area: highest
      degrees of true ptosis, deflated and flattened glands, and totally inelastic
      covering tissues. Plastic surgeons need an easy-to-use algorithm for technical
      choices. METHODS: Ptosis and volume loss are the main problems to be corrected on
      massive-weight-loss (M.W.L.) breasts. Both problems need specific resolutions due
      to their specific characteristics. Depending on the degree of ptosis and the
      amount of volume loss, a decisional algorithm has been developed: suitable and
      advisable techniques are pointed out, minimizing the risk/benefit ratio. "Pros
      and cons" with the use of mammary implants are emphasized. RESULTS: A group of
      195 postbariatric surgery patients underwent breast contouring since 2001
      following the herein presented decisional algorithm. Results have been tested
      with Body Uneasiness Test: encouraging data pushed to continue this method and to
      refine it. CONCLUSIONS: Referring to this strategy algorithm, choices 2 and 3
      appear to be the more frequently applied and better fitted to cover the majority
      of M.W.L. breast defects. In the future, the birth and the rise of new mammary
      implant concepts and technologies could completely change this algorithm.

PMID- 20054716
TI  - Heparin-induced thrombocytopenia and cerebral venous sinus thrombosis: case
      report and literature review.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT)-related cerebral venous sinus
      thrombosis (CVST) has been described in 10 prior case reports in the English
      language medical literature. We report the first case of low molecular weight HIT
      related CVST with detailed clinical course and novel therapeutic approach.
      METHODS: A 69-year-old woman presented with a focal seizure after total hip
      replacement. Enoxaparin for venous thromboembolism prophylaxis had been initiated
      8 days prior to the seizure. RESULTS: The patient experienced progressive
      neurologic deterioration, and MRI and CT angiography were consistent with
      cerebral sinus thrombosis (CVST). The new onset of thrombocytopenia, thrombosis,
      and positive heparin ELISA (enzyme-linked immunosorbent assay) and SRA (serotonin
      release assay) assays confirmed HIT. In spite of aggressive management of HIT
      related CVST, including argatroban therapy and endovascular mechanical
      thrombolysis, the patient expired. CONCLUSIONS: A review of the previous 10 case
      reports in the literature confirms that HIT-related CVST is often a fatal
      condition, particularly when diagnosed in comatose patients. Because the
      diagnosis is rare and often delayed relative to initial presentation, prevention
      is the key to improve patient outcomes. Newer anticoagulants with different
      mechanism of action than heparin are currently under review by the FDA; they will
      facilitate prevention of HIT-related CVST and other HIT-related neurological
      complications.

PMID- 20054717
TI  - Clear cell adenocarcinoma of the uterine cervix in a young pregnant woman: a case
      report with immunohistochemical study.
AB  - The patient was a 30-year-old-pregnant woman (para 1, gradiva 1) without in utero
      exposure to diethylstilbestrol. A papillary and flat lesion was found by
      colposcopy in the uterine cervix in the routine examination at 10 pregnancy
      weeks. Biopsies showed papillary and tubular proliferation of malignant cells
      with clear glycogen-rich cytoplasm and malignant hobnail cells and were diagnosed
      as clear cell adenocarcinoma. The patient was treated by radical hysterectomy.
      The lesion of the cervix (10 * 15 * 5 mm) was clear cell adenocarcinoma with mild
      invasion into shallow myometrium (pTIb). An immunohistochemical study showed that
      the tumor cells were positive for pancytokeratins (AE1/3, CAM5.2, KL-1, and
      polyclonal wide), cytokeratin (CK) 7, CK8, CK18, CK19, epithelial membrane
      antigen, CA 125, p53 protein, and Ki-67 antigen (labeling = 95%). The tumor cells
      were negative for high-molecular weight CK (34betaE12), CK5/6, CK14, CK20,
      vimentin, AFP, CEA, desmin, S100 protein, alpha-smooth muscle antigen, CD34,
      estrogen receptor, progesterone receptor, chromogranin, synaptophysin, neuron
      specific enolase, and CD56. The patient is now of free of tumor. In the English
      literature, the present case is the second case of cervical clear cell
      adenocarcinoma during pregnancy, and the first case of cervical clear cell
      carcinoma investigating a wide range of immunoreactive antigens.

PMID- 20054718
TI  - Education, economic status and other risk factors in gastric cancer: "a case
      control study of Turkish Oncology Group".
AB  - Diet and lifestyle related to socioeconomic status emerged as risk factors for
      gastric cancer in several studies. However, the results were not always
      consistent with the socioeconomic status. The aim of this study was to evaluate
      the risk factors independent from education as a measure of socioeconomic status.
      Two hundred and fifty-three patients with gastric cancer diagnosed in 2005 and
      equal number of control subjects were interviewed for several characteristics and
      diet. Matching was done for age, gender, city of residence and also for the level
      of education. Despite these matching preferences, patients had significantly
      lower income when compared to the control subjects (P = 0.0001). Higher rate of
      patients were smoking more than 2 packs/day of cigarettes (P = 0.018). Also
      significantly higher rate of control subjects were using antibiotics (P = 0.002).
      Coffee (P < 0.0001), salad (P = 0.006), bread (P = 0.005), vegetable-derived
      cooking oil (P = 0.003) consumptions appeared as highly protective factors
      against gastric cancer in univariate analysis in the present trial. In
      multivariate analysis, significant risk reducing factors were bread (P = 0.005)
      and coffee consumption (P = 0.0001) other than the level income (P = 0.002). In
      conclusion, the goal of obtaining comparable socioeconomic status by including
      the level of education in the matching criteria was not met in our study because
      of the difference in income level. The only risk reducing factor that was not in
      accordance with income level was the unexpectedly higher rate of bread
      consumption in control group.

PMID- 20054719
TI  - Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian
      cancer cells.
AB  - Ovarian cancer is a leading cause of cancer-related women mortality in China. In
      recent years, the molecular mechanisms involved in ovarian carcinoma development
      and/or progression have been intensely studied, and several genes have been
      identified. Deleted in Colorectal Carcinoma (DCC), is an important tumor
      suppressor gene, which is inactivated in many kinds of tumors, and its
      function(s) is not clarified. Even though the lost expression of DCC occurred in
      later stages of multistep colorectal carcinogenesis, its contribution to the
      onset or progression of ovarian cancer is not fully understood. To investigate
      DCC expression in ovarian cancer, we studied 254 clinical samples by RT-PCR. Our
      results revealed that 52% malignant ovarian cancer did not express DCC gene. By
      contrast, DCC expression was observed in all normal ovary tissues and 80% benign
      ovarian tumors. Obviously, there was a significant correlation between DCC
      expression and ovarian cancer, especially in the epithelial ovarian cancer. The
      present study also suggested that the loss expression of DCC occurred more
      frequently in the cases of later clinical stage, higher pathological grade, and
      poorer prognosis. In the other part of this study, we further explored DCC
      expression after transfection in two kinds of ovarian cancer cell lines, namely
      SKOV3 cell and HO-8910 cell, using RT-PCR and immunocytochemistry. The results
      indicated that DCC expressed in SKOV3-DCC and HO-8910-DCC cells, and
      ultrastructural analysis showed the appearance of apoptotic features in them.
      Furthermore, cell growth was markedly down-regulated in above groups of cells,
      indicating that transfection with the DCC constructs can suppress the growth of
      tumor cells. In conclusion, our results suggest an association of lost expression
      of DCC with the ovarian cancer, and DCC gene may inhibit the growth of ovarian
      carcinoma cells. However, this result needs further trials with a larger sample.

PMID- 20054720
TI  - Exercise does not increase cyclooxygenase-2 myocardial levels in young or
      senescent hearts.
AB  - Increased myocardial cyclooxygenase-2 (COX-2) activity is essential for late
      phase ischemic preconditioning (IPC). Currently unknown is whether
      cardioprotection elicited by exercise also involves elevated myocardial COX-2
      activity. This investigation tested whether aerobic exercise elevates myocardial
      COX-2 protein content or enzyme activity in young and senescent male Fisher 344
      rats assigned to sedentary or cardioprotective endurance exercise treatments (3
      consecutive days of treadmill exercise, 60 min/day @ approximately 70% VO(2)max).
      Assay of cardiac COX-2 protein content, catalytic activity, and inducible nitric
      oxide synthase (iNOS) protein content reveal that exercise did not alter COX-2
      activity (PGE(2), p = 0.866; PGF1alpha, p = 0.796) or protein levels (p = 0.397)
      within young or senescent hearts. In contrast, myocardial iNOS, an up-stream
      mediator of COX-2 expression, was over-expressed by an average of 37% in aged
      hearts (p = 0.005), though iNOS was not influenced by exercise. Findings reveal
      exercise does not elevate cardiac COX-2 activity and suggests that mechanisms
      responsible for cardioprotection differ between IPC and aerobic exercise.

PMID- 20054721
TI  - Isolated thallus-associated compounds from the macroalga Fucus vesiculosus
      mediate bacterial surface colonization in the field similar to that on the
      natural alga.
AB  - This study investigated whether surface-associated compounds isolated from the
      macroalga Fucus vesiculosus had the potential to mediate microbial and/or
      macrobial epibiosis similar to that on the natural alga. To selectively yield
      thallus-associated compounds and avoid contamination by intracellular algal
      compounds, cell lysis was monitored by surface microscopy of algal cells and
      chemical profiling of algal surface extracts by coupled gas chromatography mass
      spectroscopy. The optimized extraction resulted in polar and non-polar algal
      surface extracts. The non-polar surface extract was immobilized in hydrogel, the
      polar surface extract was homogeneously perfused through the gel to ensure a
      temporally constant delivery of polar extract components. During a 7 day field
      trial, bacterial biofilms were formed on control gels and gels featuring polar
      and/or non-polar extract components. PERMANOVA revealed that bacterial community
      profiles on controls and on gels featuring polar or non-polar extract were
      significantly different from the profile on F. vesiculosus, while the profile on
      the gels bearing both polar and non-polar extracts was not. Moreover, the polar
      surface extracts inhibited the settlement of barnacle cyprids. Considering the
      pronounced effects of bacterial biofilms on invertebrate larval settlement, these
      results suggest that algal surface chemistry affects macrofouling not only
      directly but also indirectly, via its control of biofilm formation and
      composition.

PMID- 20054722
TI  - Candida albicans biofilm formation on peptide functionalized
      polydimethylsiloxane.
AB  - In order to prevent biofilm formation by Candida albicans, several cationic
      peptides were covalently bound to polydimethylsiloxane (PDMS). The salivary
      peptide histatin 5 and two synthetic variants (Dhvar 4 and Dhvar 5) were used to
      prepare peptide functionalized PDMS using 4-azido-2,3,5,6-tetrafluoro-benzoic
      acid (AFB) as an interlinkage molecule. In addition, polylysine-, polyarginine-,
      and polyhistidine-PDMS surfaces were prepared. Dhvar 4 functionalized PDMS
      yielded the highest reduction of the number of C. albicans biofilm cells in the
      Modified Robbins Device. Amino acid analysis demonstrated that the amount of
      peptide immobilized on the modified disks was in the nanomole range. Poly-d
      lysine PDMS, in particular the homopeptides with low molecular weight (2500 and
      9600) showed the highest activity against C. albicans biofilms, with reductions
      of 93% and 91%, respectively. The results indicate that the reductions are
      peptide dependent.

PMID- 20054723
TI  - Exploring Indian women's reproductive decision-making regarding prenatal testing.
AB  - Pregnant women in large cities and small towns of India are increasingly
      undergoing prenatal testing (PNT) on the advice of medical practitioners to
      ensure foetal health and to prevent the birth of disabled children. In the last
      two decades, several studies have been conducted in India to determine the extent
      of proliferation of PNT for sex selection, the profile of women/couples who avail
      themselves of it and their attitudes towards it, but hardly any research exists
      which studies women's use of PNT for genetic purposes. Drawing on empirical
      research, this paper aims to identify factors and actors that influence women's
      decision-making regarding testing and whether to continue a pregnancy after PNT
      and how informed their choice is. The research shows that once placed in the role
      of autonomous and responsible decision-makers, women are making very pragmatic
      decisions, although the information they possess is highly inadequate and
      incomplete and their life circumstances too constraining.

PMID- 20054724
TI  - Aging and the perception of emotion: processing vocal expressions alone and with
      faces.
AB  - This study investigated whether the difficulties older adults experience when
      recognizing specific emotions from facial expressions also occur with vocal
      expressions of emotion presented in isolation or in combination with facial
      expressions. When matching vocal expressions of six emotions to emotion labels,
      older adults showed worse performance on sadness and anger. When matching vocal
      expressions to facial expressions, older adults showed worse performance on
      sadness, anger, happiness, and fear. Older adults' poorer performance when
      matching faces to voices was independent of declines in fluid ability. Results
      are interpreted with reference to the neuropsychology of emotion recognition and
      the aging brain.

PMID- 20054725
TI  - Transfer of instances in cognitive skill learning: adult age differences.
AB  - Two experiments assessed the utilization of pretrained problem-solution
      associations (i.e., instances) in memory-based cognitive skill learning in
      younger and older adults. In Experiment 1, participants were given practice with
      repeated alphabet-arithmetic problems and then trained on a compound skill
      learning task that incorporated the pretrained alphabet-arithmetic items. In
      Experiment 2, participants were pretrained with compound problems, and then
      trained on just the alphabet-arithmetic items that were part of the compound
      problems. In both experiments, utilization of pretrained instances was much
      greater for younger adults than for older adults. These findings can be taken to
      imply that failure to retrieve and apply reoccurring instances is a primary
      source of age-related deficits in the transfer of cognitive skill learning across
      task situations.

PMID- 20054726
TI  - The effects of age, control beliefs, and feedback on self-regulation of reading
      and problem solving.
AB  - The authors examined the effects of adult age and control beliefs on self
      regulatory responses to feedback using a false-feedback paradigm. Young and older
      adults read and attempted to solve a series of problems and periodically received
      either high- or low-performance feedback. Self-regulatory processes were assessed
      in terms of task-specific beliefs consisting of self-efficacy and performance
      expectations as well as degree of attention allocated to reading the mysteries.
      Results showed that high-performance feedback increased self-efficacy and
      performance expectations relative to low-performance feedback and that these
      effects were comparable across levels of preexisting control beliefs and across
      age groups. However, the effects of feedback on attention were moderated by age
      and preexisting control beliefs. Older adults in the high-performance feedback
      condition who had high levels of control beliefs allocated more attention to the
      text than did their low-control peers. These findings suggest that positive
      feedback may encourage older adults to engage more fully in a reading task, but
      only when they possess a strong sense of control.

PMID- 20054727
TI  - Age-related decline in olympic triathlon performance: effect of locomotion mode.
AB  - This study describes the decline in performance with age during Olympic triathlon
      Age Groups World Championships among the different locomotion modes. Mean
      performance of top 10 performers were analyzed for each group of age using the
      exponential model proposed by Baker, Tang, and Turner (2003, Experimental Aging
      Research, 29, 47-65). Comparison in performance decline was done between
      locomotion modes. Decline in performance in triathlon as a function of age
      follows an exponential model. A significant interaction effect between age and
      locomotion mode was observed on performance values. In swimming, a significant
      decrease was observed close to 5% per year after 45 years. Decline in performance
      was less pronounced in cycling until 60 years. Analysis of the effect of age in
      the different locomotion modes of a triathlon could provide information for
      maintaining quality of life with aging.

PMID- 20054728
TI  - Genetic regulatory network analysis for app based on genetical genomics approach.
AB  - A number of studies have shown that amyloid precursor protein (App) plays a
      critical role in Alzheimer's disease (AD); however, little is known about the
      genetic regulatory network. In this study, the authors combined array analysis
      and quantitative trait loci (QTL) mapping to characterize the genetic variation
      and genetic regulatory network for App using hippocampus of BXD recombinant
      inbred (RI) mice. The variation in expression level of App is conspicuous across
      the 78 BXD RI strains. Moreover, the expression level of App is significantly
      higher in DBA/2J than the level in C57BL/6J (p < .001). Quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR) analysis has further confirmed
      the significant difference between the two parental strains C57BL/6J and DBA/2J.
      The authors performed an interval mapping for App gene expression and found that
      it is cis regulated with highly significant likelihood-ratio statistic (LRS)
      score (LRS = 19; p < .05). Four SNPs and two InDels (insertions or deletions)
      were identified in the promoter, and one of the SNPs is located in the pax2
      motif. Genetic regulatory network analysis showed that App coregulated with many
      AD-related genes, including Gsk3b, Falz, Mef2a, Tlk2, Rtn, and Prkca. The
      genetical genomics approach demonstrates the importance and the potential power
      of the expression quantitative trait loci (eQTL) studies in identifying
      regulatory network that contribute to complex traits, such as AD.

PMID- 20054729
TI  - Gender differences in mental rotation across adulthood.
AB  - Although gender differences in mental rotation in younger adults are prominent in
      paper-pencil tests as well as in chronometric tests with polygons as stimuli,
      less is known about this topic in the older age ranges. Therefore, performance
      was assessed with the Mental Rotation Test (MRT) paper-pencil test as well as
      with a computer-based two-stimulus same-different task with polygons in a sample
      of 150 adults divided into three age groups, 20-30, 40-50, and 60-70 years.
      Performance decreased with age, and men outperformed women in all age groups. The
      gender effect decreased with age in the MRT, possibly due to a floor effect.
      Gender differences remained constant across age, however, in the error rates of
      the computer-based task.

PMID- 20054730
TI  - Supplementing cognitive aging: a selective review of the effects of ginkgo biloba
      and a number of everyday nutritional substances.
AB  - This review concerns a number of substances that have been receiving much
      attention, particularly in the media, for their potential to protect against age
      related cognitive decline, and a focus is placed upon recent findings. Omega-3
      fatty acids appear to play important roles in preserving neuronal structure and
      function and minimizing cognitive decline, whereas the antioxidant vitamins C and
      E appear to be particularly beneficial for combating age-related oxidative stress
      when administered in combination. Fruit and vegetable polyphenols also offer
      great potential, although most research thus far has involved rodents. Finally,
      there is mixed evidence regarding the cognitive enhancing properties of Ginkgo
      biloba, and the B vitamins folate and cobalamin, with all of these requiring
      further investigation.

PMID- 20054731
TI  - Addressing the need for healthcare and hospital services.

PMID- 20054732
TI  - Alternative quality measures and profitability of hospital inpatient services
      offered.
AB  - In this analysis, we study the relationship between hospital quality and hospital
      profits for a sample of 88 Alabama (USA) hospitals. Quality is measured by three
      groups of procedures performed on newly admitted patients as suggested by the
      Center for Medicare and Medicaid Services and the Health Quality Alliance (HQA)
      as well as a weighted quality measure. Profit is measured for eight hospital
      services. Profits from cardiac care were most responsive to the quality measures
      studied. Moreover, profits from six of the inpatient services increased as the
      weighted quality measure increased. Finally, in two cases quality increased with
      the relative number of employees a hospital utilized.

PMID- 20054733
TI  - A model for reducing health care employee turnover.
AB  - Explaining the rationale as to why employees leave their jobs has led to many
      different strategies to retain employees. The model presented here seeks to
      explain why employees choose to stay or to leave their place of employment. The
      information from the analysis will provide managers with well-tested tools to
      reduce turnover and to ascertain what employees value from their work environment
      in order to help the organization to retain those employees. The model identifies
      key factors that management can utilize to provide barriers to exit and retain
      professional employees in their health care units. Recommendations are provided
      that reward loyalty and build barriers to exit.

PMID- 20054734
TI  - Physician offices marketing: assessing patients' views of office visits.
AB  - Physician offices often lack the sense of incorporating appropriate strategies to
      make their facilities as marketer of their services. The patient experience at a
      physician's office not only incorporates the care they receive from the physician
      but also the other non-healthcare related aspects, such as the behavior of non
      health professionals as well as the appearance of the facility itself. This paper
      is based on a primary research conducted to assess what patients assess from a
      physician office visit.

PMID- 20054735
TI  - A decision support tool for identifying abuse of controlled substances by
      ForwardHealth Medicaid members.
AB  - OBJECTIVE: Our objective was to use Wisconsin's Medicaid Evaluation and Decision
      Support (MEDS) data warehouse to develop and validate a decision support tool
      (DST) that (1) identifies Wisconsin Medicaid fee-for-service recipients who are
      abusing controlled substances, (2) effectively replicates clinical pharmacist
      recommendations for interventions intended to curb abuse of physician and
      pharmacy services, and (3) automates data extraction, profile generation and
      tracking of recommendations and interventions. METHODS: From pharmacist manual
      reviews of medication profiles, seven measures of overutilization of controlled
      substances were developed, including (1-2) 6-month and 2-month "shopping" scores,
      (3-4) 6-month and 2-month forgery scores, (5) duplicate/same day prescriptions,
      (6) count of controlled substance claims, and the (7) shopping 6-month score for
      the individual therapeutic class with the highest score. The pattern analysis
      logic for the measures was encoded into SQL and applied to the medication
      profiles of 190 recipients who had already undergone manual review. The scores
      for each measure and numbers of providers were analyzed by exhaustive chi-squared
      automatic interaction detection (CHAID) to determine significant thresholds and
      combinations of predictors of pharmacist recommendations, resulting in a decision
      tree to classify recipients by pharmacist recommendations. RESULTS: The overall
      correct classification rate of the decision tree was 95.3%, with a 2.4% false
      positive rate and 4.0% false negative rate for lock-in versus prescriber-alert
      letter recommendations. Measures used by the decision tree include the 2-month
      and 6-month shopping scores, and the number of pharmacies and prescribers. The
      number of pharmacies was the best predictor of abuse of controlled substances.
      When a Medicaid recipient receives prescriptions for controlled substances at 8
      or more pharmacies, the likelihood of a lock-in recommendation is 90%.
      CONCLUSION: The availability of the Wisconsin MEDS data warehouse has enabled
      development and application of a decision tree for detecting recipient fraud and
      abuse of controlled substance medications. Using standard pharmacy claims data,
      the decision tree effectively replicates pharmacist manual review
      recommendations. The DST has automated extraction and evaluation of pharmacy
      claims data for creating recommendations for guiding pharmacists in the selection
      of profiles for manual review. The DST is now the primary method used by the
      Wisconsin Medicaid program to detect fraud and abuse of physician and pharmacy
      services committed by recipients.

PMID- 20054736
TI  - Virtual atmospherics: a new key to patient satisfaction.
AB  - Hospitals and other medical providers are intentional with respect to reinforcing
      desirable personal and emotional characteristics such as safety, security,
      relaxation, and comfort in the physical design and decoration of their
      facilities. For years, hospital aesthetics have been designed to reduce stress
      and provide the greatest amount of patient comfort and confidence. Given the
      explosion of Internet usage, consideration must be given to the virtual
      environment as well. Increasingly, patients use the Internet to gather medical
      information and to interact with healthcare providers; therefore, it is critical
      to reinforce desirable personal and emotional characteristics in the virtual
      environment.

PMID- 20054737
TI  - Risk and uncertainty.
AB  - Volatile business conditions have led to drastic corporate downsizing, meaning
      organizations are expected to do more with less. Managers must be more
      knowledgeable and possess a more eclectic myriad of business skills, many of
      which have not even been seen until recently. Many internal and external changes
      have occurred to organizations that have dictated the need to do business
      differently. Changes such as technological advances; globalization; catastrophic
      business crises; a more frantic competitive climate; and more demanding,
      sophisticated customers are examples of some of the shifts in the external
      business environment. Internal changes to organizations have been in the form of
      reengineering, accompanied by structural realignments and downsizing; greater
      emphasis on quality levels in product and service output; faster communication
      channels; and a more educated, skilled employee base with higher expectations
      from management.

PMID- 20054738
TI  - The effect of bilateral asymmetry of muscle strength on jumping height of the
      countermovement jump: a computer simulation study.
AB  - The purpose of the current study was to examine the effect of bilateral asymmetry
      of muscle strength on performance (maximal jumping height) of the countermovement
      jump. In experimental studies, it is impossible to control for muscle strength
      asymmetry, since it varies widely among individuals. In the current study, we
      used computer simulation. Two three-dimensional human lower limb
      neuromusculoskeletal models (model-symmetry and model-asymmetry) were developed.
      The total muscle strength of the two models was set to be identical. Bilateral
      muscle strength was set equal in the model-symmetry simulation, while the model
      asymmetry simulation was set with a 10% bilateral strength asymmetry. The
      countermovement jumps were generated successfully, producing jumping heights of
      0.416 m for model-symmetry and 0.419 m for model-asymmetry. The small difference
      in height (0.7%) indicates that bilateral asymmetry by itself does not have a
      significant effect on jumping performance. With model-asymmetry, the strong leg
      compensated for the muscle strength deficit of the weak leg by lateral movement
      of the body to distribute the load proportional to the muscle strength of each
      leg.

PMID- 20054739
TI  - Effect of quercetin supplementation on maximal oxygen uptake in men and women.
AB  - Quercetin is a naturally occurring flavonoid with anti-oxidant and anti
      inflammatory properties. The effect of quercetin supplementation on maximal
      oxygen uptake (VO(2max)) is unknown. The purpose of this investigation was to
      test the effects of quercetin supplementation on VO(2max) in untrained, sedentary
      individuals. After baseline treadmill VO(2max) testing, 11 participants (5 males,
      6 females) ingested either placebo or quercetin-supplemented (1000 mg x day(-1))
      food bars in a randomized, double-blind, counterbalanced, crossover research
      design. The participants ingested food bars for six consecutive mornings (5
      days). On the sixth morning, participants underwent repeat VO(2max) testing.
      After a 22 day wash-out, the participants repeated baseline VO(2max) testing,
      daily consumption of the opposite food bars, and post-supplementation VO(2max)
      testing. The condition x time interaction for VO(2max) was non-significant when
      expressed in absolute (litres x min(-1); P = 0.929) and relative (ml x kg(-1) x
      min(-1); P = 0.778) terms. These findings were similar when taking sex into
      account (P > 0.05). The mean difference in VO(2max) change from pre to post
      between groups (quercetin vs. placebo) was 0.139 ml x kg(-1) x min(-1) (P =
      0.780). Other physiological measures also were similar between conditions (P >
      0.05). In conclusion, 5 days of quercetin supplementation did not influence
      VO(2max) or related variables in sedentary men and women.

PMID- 20054740
TI  - Tracking of wheelchair rugby players in the 2008 Demolition Derby trial.
AB  - The kinematics of male wheelchair rugby players (n = 8) during the final match of
      the 2008 Demolition Derby were assessed using two cameras (10 Hz) and a tracking
      method based on image-processing techniques. The players' on-court trajectory,
      total and accumulated distances covered, distances covered during working and
      stopped game clock, and average velocity were calculated. The players covered
      2294.7 +/- 391.5 m in the first half and 2245.4 +/- 431.5 m in the second half.
      The average velocity was 14.5% greater in the first (1.22 +/- 0.21 m . s(-1))
      than in the second half (1.05 +/- 0.20 m . s(-1)). The reduction in velocity was
      most marked in players with less functional capacity. The working game clock
      represented 48% of total game time (32 of 66.8 minutes) and the distance covered
      by all players during working game clock was 60% of the overall distance covered
      during the whole game (36,323 m). The results provide new information regarding
      the dynamics of a wheelchair rugby match and should aid coaches in planning
      effective training and coaching strategies. 

PMID- 20054741
TI  - Editorial.

PMID- 20054742
TI  - Emery-Dreifuss dystrophy: a 4-year follow-up on a laminopathy of special
      interest.
AB  - BACKGROUND AND PURPOSE: The authors present the results of a 4-year follow-up of
      patients with Emery-Dreifuss dystrophy (EDMD) included in a project on
      laminopathies. The focus of the discussion is on the clinical and genetic
      characteristics, and the classification of the two forms of Emery-Dreifuss
      dystrophy [i.e. associated with either emerinopathy (EDMD1) or laminopathy
      (EDMD2)]. MATERIAL AND METHODS: The study includes 37 patients from 12 families
      with EDMD, 28 having emerinopathy and 9 with laminopathy. On the basis of
      findings from clinical examination and laboratory tests (24-hour ECG monitoring,
      echocardiography, histological and immunohistochemical studies of muscle), the
      authors describe phenotypes of the two forms of Emery-Dreifuss dystrophy, the
      natural course of the disease, and a possible severe cardiovascular involvement
      which may lead to severe cardiac complications and sudden death. The patients
      with EDMD were treated mainly by cardiologists. Besides symptomatic management,
      implantation of a cardiac pacemaker or cardioverter-defibrillator is often
      required. CONCLUSIONS: The intrafamilial and interfamilial variability of
      laminopathies is discussed in relation to interactions between nuclear proteins.
      Since the EDMD carrier state in females is associated with cardiac symptoms
      (without skeletal muscle involvement), systematic cardiological supervision is
      indicated. Likewise, there are certain patients presenting a typical EDMD
      phenotype in which no mutations in the EMD or LMNA genes can be confirmed. This
      may indicate that an Emery-Dreifuss-like dystrophy could also be associated with
      mutations in other genes.

PMID- 20054743
TI  - REM sleep behaviour disorder in narcolepsy.
AB  - BACKGROUND AND PURPOSE: Narcolepsy is characterized by excessive daytime
      sleepiness, cataplexy, sleep paralysis and hypnagogic hallucinations. The aim of
      the study was to evaluate the incidence of REM sleep behaviour disorder (RBD) in
      consecutive patients with narcolepsy referred to our sleep disorders centre.
      MATERIAL AND METHODS: Among patients examined because of hypersomnia, a diagnosis
      of narcolepsy was established in 30 patients (mean age 34.1 +/-13.6; 13 females,
      17 males) on the basis of clinical features, polysomnography (PSG) and Multiple
      Sleep Latency Test. Polysomnographic analysis included assessment of muscle
      activity during REM sleep, recorded from chin and anterior tibialis muscles.
      Video recordings were reviewed for intense motor activity during REM periods,
      manifested as excessive, violent body movements (especially legs) and
      vocalization, reflecting dream-enacting behaviour. Questions about RBD symptoms
      were asked as a standard in all newly diagnosed patients and those reporting for
      follow-up visits. RESULTS: Symptomatic, polysomnographically documented RBD was
      found in three patients. In one of them RBD symptoms appeared during
      anticataplectic treatment with antidepressive medications. Disturbances of muscle
      tone regulation during REM sleep without clinical symptoms were found in
      polysomnography in a further four patients. Among patients reporting for follow
      up visits, three subjects confirmed clinical symptoms corresponding to RBD of
      various severity. CONCLUSIONS: RBD occurs in narcolepsy more frequently than it
      was previously considered. Questions about symptoms of this disorder that may be
      injurious for the patient or patient's bed partner should be routinely asked
      during the clinical interview.

PMID- 20054744
TI  - Does amantadine have favourable effects on fatigue in Persian patients suffering
      from multiple sclerosis?
AB  - BACKGROUND AND PURPOSE: Fatigue is a frequent symptom in multiple sclerosis (MS),
      recognized as the most unpleasant symptom by 50-60% of patients. Amantadine is
      one of the medications prescribed for fatigue in MS. Some previous studies have
      demonstrated a positive influences of amantadine on fatigue in MS. The aim of
      this study was to determine the efficacy of amantadine on Persian MS patients.
      MATERIAL AND METHODS: This prospective study took place in Isfahan, Iran and
      included 42 MS patients with fatigue who were divided randomly into two groups.
      Twenty-one patients received amantadine and all others placebo. The Fatigue
      Severity Scale (FSS) was used to determine the severity of the fatigue. FSS
      scores at baseline and two months later were compared in the two groups. RESULTS:
      Mean (SD) baseline FSS score was 5.27 (1.11) in the amantadine group and 4.89
      (1.13) in the placebo group (p > 0.05). Mean FSS at the end of study was 4.00
      (1.02) in the amantadine group and 4.24 (1.03) in the placebo group (p > 0.05);
      however, the FSS change (the difference between FSS scores at the end of the
      study and at the beginning of the study) in amantadine and placebo groups was 
      1.27 (0.53) and -0.66 (0.33), respectively, which was significant (p < 0.05).
      CONCLUSIONS: Our findings demonstrate a significant drop on the fatigue severity
      scale in MS patients after treatment with amantadine; nevertheless, more studies
      on a larger scale with longer duration are needed to confirm this finding.

PMID- 20054745
TI  - Comparison of the diagnostic value of ultrasonography and neurography in carpal
      tunnel syndrome.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to compare the sensitivity and
      specificity of ultrasonography and neurography in patients with carpal tunnel
      syndrome (CTS) and to estimate the critical value of cross-sectional area of
      median nerves. MATERIAL AND METHODS: Eighty-nine patients (153 carpal tunnels)
      (17 men and 72 women, mean age 62.5 years) with CTS and 50 healthy volunteers
      were examined. In all patients and controls standard neurographic tests were done
      (motor and sensory conduction velocity tests in median and ulnar nerves).
      Ultrasonography was done in transverse projections with estimation of cross
      sectional circumference and area of median nerves. RESULTS: Mean parameters of
      ultrasonography and neurography, except the mean latency of sensory potentials,
      were statistically different in the patient and control groups. Correlations
      between mean parameters of ultrasonography and neurography were also
      statistically significant. The critical value of median nerves' cross-sectional
      area equal to 0.1 cm2 seemed to be important in CTS diagnostics. Oedema of median
      nerve was observed in some CTS cases without electrophysiological changes. Radial
      slide of median nerve round the tendon of superficial flexor muscles of second
      and third fingers was observed in 68% of CTS patients. CONCLUSIONS:
      Ultrasonographic findings correlate well with electrophysiological tests in CTS
      patients. Cross-sectional area equal to 0.1 cm2 is important in CTS diagnostics.
      Median nerve oedema, revealed in the early stage of CTS without any
      electrophysiological changes, might be an important factor in occurrence of
      subjective complaints. Radial slide of median nerve phenomenon is a common
      ultrasonographic finding in CTS.

PMID- 20054746
TI  - Index finger somatosensory evoked potentials in blind Braille readers.
AB  - BACKGROUND AND PURPOSE: Traditionally, vision has been considered the dominant
      modality in our multi-sensory perception of the surrounding world. Sensory input
      via non-visual tracts becomes of greater behavioural relevance in totally blind
      individuals to enable effective interaction with the world around them. These
      include audition and tactile perceptions, leading to an augmentation in these
      perceptions when compared with normal sighted individuals. The objective of the
      present work was to study the index finger somatosensory evoked potentials (SEPs)
      in totally blind and normal sighted individuals. MATERIAL AND METHODS: SEPs were
      recorded in 15 Braille reading totally blind females and compared with 15 age
      matched normal sighted females. Latency and amplitudes of somatosensory evoked
      potential waveforms (N9, N13, and N20) were measured. RESULTS: Amplitude of N20
      SEP (a cortical somatosensory evoked potential) was significantly larger in the
      totally blind than in normal sighted individuals (p < 0.05). The amplitudes of N9
      and N13 SEP and the latencies of all recorded SEPs showed no significant
      differences. CONCLUSIONS: Blindness has a profound effect on the Braille reading
      right index finger. Totally blind Braille readers have larger N20 amplitude,
      suggestive of greater somatosensory cortical representation of the Braille
      reading index finger.

PMID- 20054747
TI  - [Optimisation of treatment of Parkinson's disease with levodopa].
AB  - This article presents the major strategies for individualisation and optimisation
      of levodopa therapy. The relationship between pharmacokinetic and pharmacodynamic
      effects of levodopa is discussed. Pharmacokinetic parameters in different stages
      of Parkinson's disease are interpreted. Moreover, the main differences in
      pharmacokinetics of levodopa formulations and routes of administration are
      presented. The authors also suggest methods to increase efficacy and safety of
      levodopa therapy in patients with Parkinson's disease.

PMID- 20054748
TI  - [Transcranial magnetic stimulation in the therapy of selected post-stroke
      cognitive deficits: aphasia and visuospatial hemineglect].
AB  - Over the last several years functional neuroimaging studies and
      neurophysiological investigations have provided greater insight into the
      mechanisms underlying neuroplasticity and recovery after stroke. Various
      techniques became available for the non-invasive modulation of human brain
      activity and allowed better rehabilitation programmes to be designed. One of
      these new techniques is transcranial magnetic stimulation (TMS). It is a painless
      brain stimulation technique that modulates cortical activity. Regularly repeated
      TMS delivered to a single scalp position (repetitive TMS, rTMS) has an effect on
      cortical excitability that lasts beyond the duration of the rTMS applications.
      The effects of rTMS on cortical excitability may be inhibitory or facilitatory
      depending on stimulation parameters. A growing number of studies consider rTMS as
      a potential therapeutic technique in neurological disorders. This method can be
      used as a complementary treatment to conventional therapy based on training of
      disturbed functions. In this review, we cite studies indicating that sessions of
      rTMS could improve some of the cognitive symptoms after stroke.

PMID- 20054749
TI  - Epidural tuberculosis involving the entire spine.
AB  - We discuss an elderly male who developed severe back pain, rapidly progressing
      paraparesis and urinary retention consequent to L5-S1 spinal tuberculosis with
      dissemination of epidural tubercular abscess and granulation tissue to the
      cervical, thoracic, lumbar and sacral region. The initial diagnosis of lumbo
      sacral pathology with high thoracic extension was tackled by an L5 laminectomy
      and decompression along with saline flushing and evacuation of the thoraco-lumbar
      and sacral epidural abscess with the aid of a catheter passed superiorly and
      inferiorly. He developed neck pain and upper limb weakness subsequently and was
      found to have extensive extradural cervical compression by granulation tissue. He
      underwent C4-7 laminectomy and decompression of the cord. He was started on four
      drug anti-tubercular treatment. At 6-month follow-up, he had marked neurological
      improvement. MRI screening of the entire spine showed complete resolution of the
      disease. Contiguous epidural involvement of the entire spine by tubercular
      pathology has never been reported before. We suggest that screening of the entire
      spine should be considered in select cases of spinal tuberculosis based on
      symptomatology.

PMID- 20054750
TI  - Clinical, pathological and radiological features of paraspinal textiloma: report
      of two cases and review of the literature.
AB  - Textiloma is a term used for retained cottonoid or surgical sponge in the
      operation field. Although they occur mostly after thoracic or abdominal
      operation, they can also be encountered after surgery of extremities or the
      spine. There are few reports of spinal cases in which MR and CT imaging findings
      of textilomas have been described. In this report, two additional cases with MR,
      CT and pathological features of paraspinal textilomas are described. CT image
      demonstrated a paraspinal mass simulating a malignant tumour. While T1-weighted
      MR images showed the masses with low signal intensity, T2-weighted MR images
      showed heterogeneous masses with low and high signal intensities.

PMID- 20054751
TI  - Sphenoid wing meningioma and glioblastoma multiforme in collision - case report
      and review of the literature.
AB  - The coexistence of two histologically different primary tumours in the same brain
      region is relatively rare. The situation where these tumours in collision appear
      in an area of a previously excised meningioma is even more rare and only two
      cases have been reported so far. We present the third case of a 73-year-old woman
      who underwent an uneventful excision of a right sphenoid wing meningioma. She was
      re-admitted 3 years later due to reappearance of a tumour in the area adjacent to
      the previously excised meningioma. Histological diagnosis revealed a collision
      tumour of a glioblastoma multiforme and a fibrillary meningioma. The coincidence
      of these two different neoplasms in the same location at the same time 3 years
      after surgical removal of a meningioma leads us to speculate on the pathogenesis,
      and to review the literature regarding this particular issue.

PMID- 20054752
TI  - [Multiple mononeuropathy in the course of the Churg-Strauss syndrome--a case
      study].
AB  - The Churg-Strauss syndrome (CSS) is a systemic vasculitis. The symptoms of CSS
      normally occur between the ages of 20 and 40. We present a case of a 60-year-old
      man with the CSS evolving in three phases. The initial symptoms included
      bronchial asthma and inflammation of the ethmoid sinuses. Later, the patient was
      diagnosed with peripheral blood eosinophilia, pulmonary changes, skin changes and
      neurological symptoms that progressed to multiple mononeuropathy.
      Electrophysiological tests confirmed progressive damage of the peripheral nervous
      system. An improvement of the patient's neurological state was observed after
      application of corticosteroids and rehabilitation. CSS is one of the causes of
      multiple mononeuropathy and should be taken into account in differential
      diagnosis. In patients with bronchial asthma, hypereosinophilia and progressive
      damage of many nerves, the syndrome is diagnosed in accordance with the criteria
      defined by the American College of Rheumatology.

PMID- 20054753
TI  - Predictors of long-term treatment effect of rivastigmine in Alzheimer's disease:
      a role for beta-amyloid plasma levels?
AB  - BACKGROUND AND PURPOSE: Cholinesterase inhibitors (ChEI) are currently the
      mainstream symptomatic treatment of patients with Alzheimer's disease (AD). To
      this end, the response to the treatment with ChEI is clinically difficult to
      predict. Several demographic, clinical and biological variables have been
      proposed as pre-treatment predictors of long-term therapy efficacy. The aim of
      the study was to confirm our initial observations of the significance of a change
      in plasma levels of beta-amyloid (Abeta) peptides after initial treat-ment with
      rivastigmine for predicting clinical response to ChEI. MATERIAL AND METHODS:
      Fifty-four carefully selected subjects (37 females) satisfying criteria for mild
      (n = 25) or moderate (n = 29) AD were included in the study. Rivastigmine was
      prescribed at the initial dose of 3 mg/day b.i.d.; the dose was escalated to the
      maximum tolerated one in at least 4-week intervals. The response to treatment was
      assessed using the ADAS-Cog and CDR scales. Whole blood samples were collected
      twice: before the first rivastigmine dose and at the 2nd week on active
      treatment. Levels of Abeta(1-40) and Abeta(1-42) were measured in plasma using a
      commercially available ELISA. RESULTS: We confirmed that higher initial disease
      severity (higher ADAS-Cog scores) and the increase in the con-centration of
      plasma Abeta(1-42) peptide following 2 weeks of treatment with an initial dose of
      rivastigmine increased the chance of a clinically meaningful response to ChEI
      therapy in AD patients after 2 years of follow-up. CONCLUSIONS: A change in
      plasma Abeta(1-42) level might constitute a novel biochemical predictor of long
      term rivastigmine treatment efficacy in AD.

PMID- 20054754
TI  - Health-related quality of life in Iranian patients with multiple sclerosis: a
      cross-cultural study.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate aspects of health-related
      quality of life (HRQoL) of patients with multiple sclerosis (MS) who live in
      Tehran and to compare data with evaluations of both the general population and MS
      patients in other countries. MATERIAL AND METHODS: One hundred and forty patients
      with MS, yet without severe comorbidity, were selected according to convenience
      sampling in a cross-sectional study. Data were collected by means of the SF-36
      questionnaire and Beck Depression Inventory (BDI). The Expanded Disability Status
      Scale of Kurtzke (EDSS) and Mini Mental State Examination were recorded for all
      patients. RESULTS: The mean age of the participants was 34.7 years. For all SF-36
      scales, MS patients were found to have lower scores, after adjustment for sex and
      age, compared with the general population. BDI and EDSS scores were significantly
      and negatively correlated with all of the SF-36 scales. Moreover, the BDI and
      EDSS were found to be positively correlated with one another (r = 0.415, p <
      0.01). CONCLUSIONS: The findings strongly confirm that patients with MS suffer
      from poor HRQoL. Depression had a strong effect on HRQoL and in order to improve
      HRQoL in MS patients the prevention and treatment of depression is vital.

PMID- 20054755
TI  - Microembolic signals in symptomatic and asymptomatic internal carotid artery
      occlusive disease.
AB  - BACKGROUND AND PURPOSE: Cerebral microembolic signals (MES) in patients with
      carotid occlusive disease can be detected by transcranial Doppler (TCD)
      examination. The aim of this study was to determine the incidence and prevalence
      of MES in both symptomatic and asymptomatic patients with stenosis or occlusion
      of the internal carotid artery (ICA). MATERIAL AND METHODS: This study included
      40 patients (mean age 64.3 +/-11.4) with ICA stenosis or occlusion, diagnosed
      with colour Doppler duplex. TCD monitoring of the middle cerebral artery
      downstream to ICA pathology was performed for 45 minutes. Acute carotid territory
      symptoms were present in 26 (65%) patients. Each patient within this group had
      neuroimaging performed. Antiplatelet drugs were administered in 35 patients
      (87.5%). RESULTS: MES were detected in 11 patients (27.5%). Median number of MES
      in all studied patients was 0. MES were present only in patients with ICA
      stenosis l 40% and in the symptomatic group. Two patients (18.2%) with ICA
      occlusion showed MES. There was relationship between risk of MES and age (OR =
      2.7/10 years, 95% CI 1.1-6.7, p = 0.02), sex (more frequent in male: OR = 16.9,
      95% CI 1.1-259; p = 0.04) and ischaemic lesions in computed tomography (OR = 9.8,
      95% CI 1.0-99.1, p = 0.04). Antiplatelet treatment did not influence the
      occurrence of MES in the study group (OR = 1.6; 95% CI 0.1-17.4; p = 0.69).
      CONCLUSIONS: MES were detected in above 1/4 of patients and an associated with
      the degree of ICA stenosis and the presence of ischaemic lesions found in CT.
      This may suggest a correlation between MES an stroke. Plaque morphology does not
      influence the prevalence of MES.

PMID- 20054756
TI  - Morphometric characteristics of the inner and outer diameter of lumbar pedicles
      on computed tomography.
AB  - BACKGROUND AND PURPOSE: The inner pedicle diameter is very important in pedicle
      screw placement in order to achieve safe and strong posterior stabilization. The
      optimal pull-out strength can be achieved by a screw which fits into the pedicle
      medulla. The aim of the present study was to compare the inner and outer pedicle
      diameters of lumbar pedicles, to determine the inner/outer pedicle diameter
      ratios, and to develop a simple measure for estimating optimal pedicular screw
      size. MATERIAL AND METHODS: 178 lumbar pedicles of 20 patients were evaluated.
      Inner and outer pedicle diameters of lumbar vertebrae were measured in computed
      tomography (CT). A simple linear regression analysis was performed to assess the
      relationship between the inner and outer pedicle diameters. RESULTS: The widest
      pedicle outer diameter was seen at L5, with a mean of 16.538 +/- 1.899 mm. The
      narrowest pedicle outer diameter was seen at L1, with a mean of 8.310 +/- 1.870
      mm. The maximum inner pedicle diameter was at the L5 level, with a mean of 11.416
      +/- 2.664 mm, whereas the minimum was at the L1 level, with a mean of 5.510 +/-
      1.887 mm. The regression coefficient between the inner and outer pedicle diameter
      was 0.68 for all pedicles combined. CONCLUSIONS: We have demonstrated the
      relation of the inner and outer pedicle diameter of lumbar pedicles and described
      an easy and reliable method to estimate the inner pedicle diameter from the outer
      diameter on CT.

PMID- 20054757
TI  - The genetics of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating disorder of still unknown
      aetiology and pathogenesis. It is characterized by a progressive and selective
      loss of motor neurons in the brain and spinal cord. The majority of ALS cases
      (90%) are sporadic and in approximately 10% the disorder is familial. In the
      light of recent studies, the familial forms might however be more frequent. The
      article describes mutations of genes linked to both sporadic and familial ALS and
      the role of the proteins they encode.

PMID- 20054758
TI  - [Stem cell-based therapy in central nervous system diseases].
AB  - Much of the current research into stem cell biology is focused on its potential
      for regeneration of various tissues and organs. Stem cell-based therapy with
      autologous bone marrow stem cells could provide an attractive alternative to the
      classical therapeutic approach in the foreseeable future. The possibility of
      nervous tissue regeneration in neurodegenerative disorders of the central nervous
      system generates a special challenge for researchers and clinicians involved in
      that field of medicine. Very small embryonic-like stem cells (VSEL SCs), recently
      discovered in murine bone marrow and human umbilical cord blood, arouse great
      hope. VSEL SCs display several features typical for embryonic stem cells, such as
      a large nucleus surrounded by a narrow rim of cytoplasm, euchromatin, and
      expression of pluripotent markers (Oct-4, Nanog, SSEA-4). Application of these
      cells in regenerative medicine could have considerable advantages over strategies
      using embryonic stem cells, since ethical concerns might be naturally solved.
      Thus, these cells can become a recommended source of stem cells for cell therapy
      as compared to those isolated from developing embryos.

PMID- 20054759
TI  - [Deep brain stimulation in the surgical management of major depressive disorder
      and obsessive-compulsive disorder].
AB  - Despite significant advances in psychopharmacology, many patients with
      psychiatric disorders remain severely impaired by their conditions in their
      private, professional and social lives. Deep brain stimulation (DBS) is a proven
      method of surgical management of Parkinson's disease, dystonia and essential
      tremor. Electrodes implanted in deep brain structures have a direct
      neuromodulatory effect on neuronal structures responsible not only for movement
      disorders but also for psychiatric disorders. The stereotactic targets for
      psychiatric disorders include limbic parts of the nuclei of the limbic neuronal
      loop. At present, DBS is applied to treat medically refractory obsessive
      compulsive disorder, depression and Tourette syndrome in small groups of
      patients. This overview includes the rationale for the use of DBS in psychiatric
      disorders, a summary of preliminary research done to date, and a discussion of
      achieved results.

PMID- 20054760
TI  - Acute respiratory distress syndrome as a manifestation of brain stem tumour--a
      case report.
AB  - Acute lung injury (ALI), including acute respiratory distress syndrome (ARDS), is
      a critical condition consisting of acute hypoxaemic respiratory failure with
      bilateral pulmonary infiltrates of non-cardiogenic origin. Occasionally it
      develops in patients with acute or subacute central nervous system pathologies,
      such as increased intracranial pressure and brain stem lesions. The exact
      epidemiology of neurogenic pulmonary oedema is unknown. However, due to non
      specific clinical manifestation it often remains undiagnosed. Its pathogenesis
      probably involves overactivation of the sympathetic autonomic system with
      pulmonary hypertension and increased vessel permeability. We present a case of
      successfully managed ARDS in a previously healthy patient with newly diagnosed
      and symptomatic haemangioblastoma of the medulla oblongata. In this context we
      also review current knowledge on the aetiopathogenesis, diagnostic criteria and
      treatment for neurogenic ARDS.

PMID- 20054761
TI  - [Sporadic hemiplegic migraine in a 14-year-old boy--a case report].
AB  - Hemiplegic migraine is a specific form of migraine with aura including
      hemiparesis. It is a rare condition of unclear aetiology. The authors present a
      case of a 14-year-old boy with persistent foramen ovale, suffering from sporadic
      hemiplegic migraine. The authors broadly describe the symptoms and types of
      hemiplegic migraine as well as underlining diagnostic and therapeutic
      difficulties of the attacks. The patient suffered from recurrent severe
      headaches, vomiting and co-existing focal neurological symptoms, including
      alternant hemiparesis. On the basis of the history, thorough clinical observation
      and numerous accessory investigations a diagnosis of sporadic hemiplegic migraine
      was established. However, the last attack, with prolonged neurological deficits,
      was treated as a complication of migraine and defined as persistent aura without
      infarction. The authors also broadly discuss a differential diagnosis, including
      other stroke-like incidents, vascular diseases, immunological and mitochondrial
      disorders that mimic the symptoms and clinical course of sporadic hemiplegic
      migraine.

PMID- 20054762
TI  - [Aortic dissection and carotid arteries dissection complicated by ischaemic
      stroke in a patient with cystic medial necrosis].
AB  - We present a case of a 62-year-old man who was admitted in grave condition to the
      Institute of Psychiatry and Neurology because of ischaemic stroke. Neurological
      examination re- vealed left-sided pyramidal hemiparesis. Computed tomography (CT)
      showed the ischaemic focus in the right cerebral hemisphere. Clinical examination
      and ultrasound examination revealed dissection of the aortic arch and
      extracranial arteries. Aortic dissection was confirmed in echocardiography and
      chest CT. The patient remained comatose and died after 7 days. Post-mortem
      examination identified dissection of the aortic arch, brachiocephalic truncus,
      common carotid arteries, internal carotid arteries and dissection extending along
      the whole aorta into both iliac arteries. This examination also showed a massive
      haemopericardium and a scar in the heart muscle after myocardial infarction.
      Microscopic examination identified cystic medial necrosis. This type of
      dissection is very rarely described.

PMID- 20054763
TI  - Abnormal indices of autonomic function are no longer predictors of poor outcome
      in diabetic patients without neuropathy but with coexisting coronary artery
      disease who receive optimal pharmacological therapy.
AB  - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a complication of
      diabetes mellitus (DM) and has been regarded as a parameter associated with a
      poor outcome. AIM: We investigated whether indices of cardiovascular autonomic
      function have prognostic value in the current era of pharmacological therapy
      recommended for DM patients with coexisting coronary artery disease (CAD), which
      consists of drugs that affect autonomic balance, i.e. angiotensin-converting
      enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and
      statins. METHODS: We studied 127 consecutive patients with type 2 DM and
      angiographically documented stable CAD (age: 64 years, women: 28%, treatment:
      ACEI/ARBs: 100%, statins: 98%, beta-blockers: 88%, insulin therapy: 46%). The
      assessment of autonomic balance within the cardiovascular system included heart
      rate variability (HRV) (time and spectral-domain analyses) and non-invasive
      evaluation of baroreflex sensitivity (sequence and controlled breathing methods).
      Primary end-points were cardiovascular mortality and urgent hospital admissions
      due to cardiovascular symptoms. RESULTS: During the mean follow-up of 502 +/- 161
      days, 28 patients (22%) experienced a cardiovascular event: 7 died and 21 were
      admitted to hospital. We found the following predictors of an increased risk of
      the combined end point (cardiovascular death and hospitalisation): elevated level
      of N-terminal BNP (for log NT-proBNP - HR = 2.6, p = 0.004), severe CAD (3-vessel
      disease - HR = 2.4, p = 0.02), renal insufficiency (eGFR < 60 ml/min/1.73 m2 - HR
      = 2.7, p = 0.008), and female gender (HR = 3.2, p = 0.002). None of the indices
      of autonomic balance had prognostic value (p > 0.2 for all). CONCLUSION: In the
      population of diabetic patients with stable CAD who receive optimal
      pharmacological therapy, indices of impaired autonomic function are no longer
      predictors of poor outcome.

PMID- 20054764
TI  - Dual antiplatelet therapy and antithrombotic treatment in patients with acute
      coronary syndrome--does everyday medical practice reflects current
      recommendations? A pilot study.
AB  - BACKGROUND: Dual antiplatelet therapy for 12 months is currently recommended for
      all patients with acute coronary syndrome (ACS), both for those treated
      pharmacologically or with percutaneous coronary interventions (PCI). Recently,
      the need for simultaneous administration of dual antiplatelet and oral
      anticoagulant therapy (triple therapy) has become more common. However, in
      addition to intensifying antiplatelet treatment, the risk of haemorrhagic
      complications is also significantly increased with triple therapy. AIM: To assess
      the in-hospital use of triple therapy in patients with ACS, who have indications
      for long-term anticoagulation, and to define the reasons for not administering
      such a therapy. METHODS: The analysis included 298 patients diagnosed with ACS
      who were admitted to our department. Analysis of recommended treatment was
      conducted upon discharge from hospital after ACS and during hospitalisation. The
      reason for discontinuation or non-compliance with oral anticoagulant (OAC)
      therapy was also assessed. RESULTS: Out of 298 patients diagnosed with ACS, 53
      (17.8%) had indications for long-term anticoagulation. The largest group
      consisted of patients with unstable angina who were treated pharmacologically
      (51.7%). The most common indication for chronic anticoagulation was paroxysmal
      atrial fibrillation (AF) (62%). At discharge from hospital, only 15.1% of
      patients received triple therapy. There was no significant association between
      the mode of treatment (triple therapy vs. lack of it) and indication for
      antiplatelet treatment (p = 0.18) or anticoagulation (p = 0.27). Among risk
      factors for bleeding, only prior episode of bleeding [p = 0.0002; odds ratio (OR)
      4.17] and treatment with PCI (p = 0.02; OR impossible to assess because of too
      small group) were significantly associated with withdrawal of triple therapy.
      CONCLUSIONS: The use of triple therapy in patients presenting with ACS and
      indications for long-term anticoagulation is insufficient. The reasons for not
      prescribing triple therapy are not clear. One explanation could be excessive
      concerns about haemorrhagic complications. There is a lack of equivocal
      guidelines and large randomised trials which would clearly define the optimal
      management strategy for patients presenting with ACS and indications for long
      term anticoagulation therapy.

PMID- 20054765
TI  - In-hospital and mid-term clinical outcomes after percutaneous coronary
      intervention with the use of sirolimus- or paclitaxel-eluting stents.
AB  - BACKGROUND: Drug-eluting stents improved the outcome after percutaneous coronary
      intervention (PCI), however, there may be significant differences in their safety
      and efficacy. AIM: To compare the in-hospital and mid-term clinical outcomes of
      stenting with sirolimus-eluting stents (SES) versus paclitaxel-eluting stents
      (PES) for the treatment of coronary artery lesions in our routine practice.
      METHODS: This study was performed on 1311 consecutive patients treated
      exclusively either with SES or PES in our hospital between March 2003 and March
      2007. Patients with acute myocardial infarction (MI) within the preceding 48
      hours were excluded. The data were recorded in our computerised database, and
      analysed with appropriate statistical methods. RESULTS: The frequency of
      angulated segments and proximal segment tortuosity was higher in the PES group (p
      = 0.001 and p < 0.001, respectively), while ostial and left anterior descending
      artery lesions were more frequently treated with SES (p < 0.001 and p = 0.022,
      respectively). The rate of in-hospital non-Q wave MI was higher in the SES vs.
      PES group (2.2 vs. 0.7%, p = 0.039). In multivariate analysis, the relationship
      between type of stent and in-hospital non-Q-wave MI became less significant (p =
      0.083). During follow-up, 5 patients in the SES vs. 3 in the PES group died (0.7%
      in each group, p = 0.749). The frequency of major adverse cardiac events (MACE)
      and target vessel revascularisation (TVR) in the SES vs. PES group was similar
      (5.5 vs. 3.3%, p = 0.138, and 2.9 vs. 1.6%, p = 0.213, respectively). In
      multivariate analysis, reference vessel diameter was an independent predictor of
      both TVR (HR = 0.170, 95% CL 0.034-0.837, p = 0.029) and MACE (HR = 0.333, 95% CL
      0.120-0.925, p = 0.035). CONCLUSION: During mid-term follow-up, sirolimus-eluting
      stents and paclitaxel-eluting stents demonstrate similar clinical outcomes.

PMID- 20054766
TI  - Changes in secondary prevention of coronary artery disease in the post-discharge
      period over the decade 1997-2007. Results of the Cracovian Program for Secondary
      Prevention of Ischaemic Heart Disease and Polish parts of the EUROASPIRE II and
      III surveys.
AB  - BACKGROUND: Both in the European and Polish guidelines, the highest priority for
      preventive cardiology was given to patients with established coronary artery
      disease (CAD). The Cracovian Program for Secondary Prevention of Ischaemic Heart
      Disease was introduced in 1996 to assess and improve the quality of clinical care
      in secondary prevention. Departments of cardiology of five participating
      hospitals serving the area of the city of Krakow and surrounding districts
      (former Krakow Voivodship) inhabited by a population of 1 200 000 took part in
      the surveys. In 1999/2000 and 2006/2007 the same hospitals joined the EUROASPIRE
      (European Action on Secondary Prevention through Intervention to Reduce Events)
      II and III surveys. The goal of the EUROASPIRE surveys was to assess to what
      extent the recommendations of the Joint Task Force of International Scientific
      Societies were implemented into clinical practice. AIM: To compare the quality of
      secondary prevention in the post-discharge period in Krakow in 1997/1998,
      1999/2000 and 2006/2007. METHODS: Consecutive patients hospitalised from 1 July
      1996 to 31 September 1997 (first survey), from 1 March 1998 to 30 March 1999
      (second survey), and from 1 April 2005 to 31 July 2006 (third survey) due to
      acute myocardial infarction, unstable angina or for myocardial revascularisation
      procedures, below the age of 71 years were identified and then followed up,
      interviewed and examined 6-18 months after discharge. RESULTS: The number of
      patients who participated in the follow-up examinations was 418 (78.0%) in the
      first survey, 427 (82.9%) in the second and 427 (79.1%) in the third survey. The
      use of cardioprotective medication increased significantly: antiplatelets from
      76.1% (1997/1998) to 86.9% (1999/2000) and 90.1% (2006/2007), beta-blockers from
      59.1% (1997/1998) to 63.9% (1999/2000) and 87.5% (2006/2007), and ACE
      inhibitors/sartans from 45.9% (1997/1998) to 79.0% (2006/2007). The proportion of
      patients taking lipid lowering agents increased from 34.0% (1997/1998) to 41.9%
      (1999/2000) and 86.8% (2006/2007). Simultaneously, a significant improvement in
      the control of hyperlipidemia could be noted. In 2006/07, over 60% had a serum
      LDL cholesterol < 2.5 mmol/l. No significant change was found in the proportion
      of subjects with well-controlled hypertension or diabetes. In 2006/2007, elevated
      blood pressure was found in 46.6% of participants and glucose > 7 mmol/l in
      13.4%. There was no significant change in smoking rates (16.3 vs. 15.9 vs.
      19.2%). The proportion of obese patients increased reaching 33.9% in 2006/2007.
      CONCLUSIONS: The implementation of CAD prevention guidelines into clinical
      practice over the decade from 1997/1998 to 2006/2007 changed significantly. The
      use of cardioprotective drugs increased largely but among risk factors a
      significant improvement could be found only in the case of hypercholesterolemia.
      No improvement in the control of hypertension and diabetes, no change in smoking
      rates and increasing prevalence of obesity suggest insufficient lifestyle
      modifications in CAD patients.

PMID- 20054767
TI  - Asymmetric dimethylarginine levels in patients with coronary artery ectasia.
AB  - BACKGROUND: Endothelial dysfunction might be one of the pathophysiological
      mechanisms in the development of coronary artery ectasia (CAE) although the exact
      mechanisms have not yet been demonstrated. Asymmetric dimethylarginine (ADMA), an
      endogenous competitive inhibitor of nitric oxide synthase, is also related to
      endothelial and structural dysfunction. AIM: To asses the relationship between
      CAE and ADMA plasma concentrations. METHODS: Thirty patients with CAE in a mean
      age of 55.5 +/- 3.6 years and 40 patients with normal coronary arteries in a mean
      age of 53.3 +/- 11.6 years were studied. The ADMA levels of all patients were
      analysed by ELISA method. RESULTS: The mean ADMA level in the CAE group was found
      to be significantly higher than the mean ADMA level in the normal coronary artery
      group (2.26 +/- 0.47 vs. 1.43 +/- 0.40 micromol/l, p < 0.001). The elevated ADMA
      level (> 1.80 micromol/l) was present in 83.0% of patients from the CAE group and
      25.0% of patients from the normal coronary artery group (p < 0.001). Having an
      increased ADMA level enhanced the risk of CAE 15-fold. The multiple-adjusted OR
      of the risk of CAE was 18.71 (95% CI 4.95-70.68) for the higher ADMA level
      compared to the lower level. CONCLUSION: Asymmetric dimethylarginine level is
      significantly associated with the presence of coronary artery ectasia. These
      findings suggest that increased ADMA level may be associated with endothelial
      dysfunction leading to the development of coronary artery ectasia.

PMID- 20054768
TI  - [Transcatheter closure of aorto-venous fistulae--is it always necessary?].
AB  - We present 2 cases (4 and 17-year-old children) with aorta-vena azygos fistulae.
      In the fist child spontaneous closure was confirmed by clinical symptoms and
      aortography, in the second (with significant left-right shunt) successful closure
      with 10 x 8 mm Amplatzer Duct Occluder was obtained. These case reports show that
      the strategy of treatment of aorto-venous fistulae must be individualised.

PMID- 20054769
TI  - A case of mitral stenosis with achalasia.
AB  - A 65-year-old woman with rheumatic heart disease and severe mitral stenosis
      developed dysphagia. As her dysphagia could not be directly attributed to an
      enlarged left atrium, she underwent barium swallow, which established the
      diagnosis of achalasia. This case report shows two unrelated diseases present in
      the same patient which individually can cause dysphagia.

PMID- 20054770
TI  - Eisenmenger syndrome and juvenile rheumatoid arthritis--a case of double
      diagnosis.
AB  - An 8.5-year-old girl evaluated for central cyanosis, hypoxia and normocarbia was
      found to have aorticopulmonary window and pulmonary hypertension. The diagnosis
      of Eisenmenger syndrome (ES) was made and treatment with bosentan was started.
      Four months later she was diagnosed to have juvenile rheumatoid arthritis and
      naproxen treatment was started. The case was remarkable in that she showed
      clinical improvement with new generation treatment of ES although pulmonary
      arterial pressure did not decrease significantly and the diagnosis of juvenile
      rheumatoid arthritis was made during follow-up.

PMID- 20054771
TI  - [Acute myocardial infarction--multivessel coronary artery disease in a 37-year
      old postpartum women].
AB  - Acute myocardial infarction (MI) in the postpartum period is rare. We present a
      case of a 37-year-old women with acute MI which occurred 15 days after delivery.
      Coronary angiography revealed multivessel coronary artery disease and she
      underwent successful surgical revascularisation.

PMID- 20054772
TI  - [Antiplatelet therapy and urgent surgical procedures. Acute appendicitis two days
      after stent implantation--a case report].
AB  - Antiplatelet therapy has become a standard primary and secondary prophylaxis
      regiment in cardiology. Perioperative coronary stent thrombosis is a catastrophic
      complication that can occur in patients with both bare-metal or drug-eluting
      stents. The most important reason of this complication is discontinuation of
      antiplatelet treatment. Non-cardiac surgery increase the risk of stent
      thrombosis, especially when it is performed early after implantation of stent.
      Since antiplatelet therapy increases the risk of bleeding but decreases the risk
      of cardio-vascular events, it is very important to consider whether to stop or to
      continue this therapy. A case of 60-year-old male patient who underwent abdominal
      operation 2 days after bare-metal stent implantation is reported. Problems with
      correct treatment are discussed.

PMID- 20054773
TI  - [From positive remodelling to coronary artery ectasia. Is coronary artery
      aneurysm a benign form of coronary disease?].

PMID- 20054774
TI  - [Role of impaired calcium homeostasis in the development of cardiac hypertrophy].

PMID- 20054775
TI  - [An isolated cleft of the anterior leaflet of the mitral valve--a case report].
AB  - A case of 44-year-old female, with an isolated mitral cleft, a rare congenital
      cause of mitral insufficiency is presented. The echocardiogram showed the
      presence of mild mitral regurgitation and a cleft of the anterior mitral valve
      leaflet was evident. Transesophageal echocardiography confirmed those findings.
      There were no other anomalies.

PMID- 20054776
TI  - [Application of paclitaxel-eluting balloon DIOR in percutaneous treatment of
      restenosis in bare metal stents--a case report].

PMID- 20054777
TI  - [Focal atrial tachycardia originating in the right atrial appendage].
AB  - We present a case of 14-year-old boy with incessant atrial tachycardia from right
      atrial appendage, resistant to pharmacotherapy and with early signs of the left
      ventricle tachyarrhythmic dysfunction. The P-wave was positive in leads I, II,
      III, aVF, negative in aVR, aVL. Moreover, P waves configuration specific for this
      localization: negative in V1-V2 that become positive in V3-V6 was present. After
      first ablation session a recurrence was observed after 3 weeks, due to inadequate
      power delivery resulting from trabeculation/anatomy that limited conventional
      ablation catheter cooling. Second ablation session with the use of an active
      electrode cooling and 3D mapping system was successful.

PMID- 20054778
TI  - Scientific teamwork--a particular approach.
AB  - The purpose of this article is to discuss the significance of academic
      collaboration within cardiovascular medicine and surgery, in both clinical and
      research settings, at a major academic institution in Europe.

PMID- 20054779
TI  - Coronary artery disease in a competitive athlete. Is running always healthy?
AB  - This case report presents a marathon runner who was diagnosed with coronary
      artery disease. We discuss the issue of evaluation of such patients with respect
      to continuation of competitive physical activity. The reported case shows that
      continued training involving above class IA-IIA sports is possible (however, long
      distance running as well?) if a subject with single vessel disease after an
      effective PCI maintains close contact with his/her doctor and obeys the rules of
      safe training. On the other hand, it supports the thesis that regular working
      out, even in professional athletes, does not guarantee 'healthy' coronary
      arteries.

PMID- 20054780
TI  - The molecular biology of senile plaques and neurofibrillary tangles in
      Alzheimer's disease.
AB  - Since the earliest descriptions of the disease, senile plaques (SP) and
      neurofibrillary tangles (NFT) have been regarded as the pathological 'hallmarks'
      of Alzheimer's disease (AD). Whether or not SP and NFT are sufficient cause to
      explain the neurodegeneration of AD is controversial. The major molecular
      constituents of these lesions, viz., beta-amyloid (Ass) and tau, have played a
      defining role both in the diagnosis of the disease and in studies of
      pathogenesis. The molecular biology of SP and NFT, however, is complex with many
      chemical constituents. An individual constituent could be the residue of a
      pathogenic gene mutation, result from cellular degeneration, or reflect the
      acquisition of new proteins by diffusion and molecular binding. This review
      proposes that the molecular composition of SP and NFT is largely a consequence of
      cell degeneration and the later acquisition of proteins. Such a conclusion has
      implications both for the diagnosis of AD and in studies of disease pathogenesis.

PMID- 20054781
TI  - Calbindin positive Purkinje cells in the pathology of human cerebellum occurring
      at the time of its development.
AB  - Development of cerebellum continues over an extremely long period of time
      extending from the early embryonic phase until the first postnatal years. During
      an extended time of maturation the cerebellum is vulnerable to harmful agents. A
      group of cytoplasmic proteins that may protect cells against injury are the
      calcium binding proteins, among others calbindin. The distribution of this
      protein is not well known in cerebellar pathology, thus in the present study the
      localisation and appearance of calbindin expressing Purkinje cells in different
      pathological conditions occurring at the time of cerebellar development was
      examined. The investigations were carried out on human maturing cerebellar cortex
      (age range 30 gestational weeks - 2 years) of cases with paraneoplastic
      cerebellar degeneration and cerebellar neuronal migration disturbances. The
      Purkinje cells located in cerebellar heterotopias and dysgenesias were
      morphologically well developed and strongly immunostained with calbindin
      antibody. In paraneoplastic cerebellar degeneration the progressive decrease of
      calbindin content and disintegration of Purkinje cells were observed. Our results
      show that intrauterine harmful agents that disturb migration of the cerebellar
      neurons do not affect the content of calbindin in misoriented neurons and that
      this protein may play a role in development of Purkinje cells located in
      heterotopias and cerebellar dysgenesias. The progressive decrease of calbindin
      content in the Purkinje cells undergoing degeneration and death during
      paraneoplastic changes in the cerebellum also supports the hypothesis that this
      protein is very important component of intracellular homeostasis in cerebellar
      neurons.

PMID- 20054782
TI  - Serum very-long-chain fatty acids levels determined by gas chromatography in the
      diagnosis of peroxisomal disorders in Poland.
AB  - Peroxisomal disorders are a large group of genetically determined metabolic
      diseases in which the biogenesis of peroxisomes is defective or there is a
      deficiency of only a single enzyme activity or substrate transporter. The
      objective of this report is to present ten years of experience in the diagnostics
      of peroxisomal disorders in Poland. Very-long-chain fatty acid (VLCFA) levels as
      a biomarker for peroxisomal defects were determined by gas chromatography in 1264
      subjects with suspicion of peroxisome disease. Peroxisome biogenesis disorders
      (PBD) were diagnosed in 8 patients, bifunctional protein deficiency in 3 and X
      linked adrenoleukodystrophy (X-ALD/AMN) in 127 hemi- or heterozygotes. The
      frequency of PBD was estimated as 0.20 : 100 000, and that of X-ALD/AMN 2.9 :
      100,000 in Poland. Mean total delay time (onset of symptoms and diagnosis) for X
      ALD/AMN was 2.2 years (range 0.25-13). High correlation of serum C26:0
      concentration and survival for PBD patient (r2 = 0.822; p < 0.001) was found.

PMID- 20054783
TI  - Severe encephalopathy with brain atrophy and hypomyelination due to
      adenylosuccinate lyase deficiency--MRI, clinical, biochemical and
      neuropathological findings of Polish patients.
AB  - Adenylosuccinate lyase (ADSL) deficiency is an autosomal recessive disorder
      caused by mutation in the ADSL gene. The disease was identified in 1984 by Jaeken
      and van der Berghe as the first inborn defect of purine biosynthesis. Affected
      children revealed encephalopathy with epilepsy and marked psychomotor
      retardation. A neurological examination showed hypotonia, followed sometimes
      after years by spasticity. The diagnosis is based on detection in the urine and
      CSF succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide ribotide
      (SAICAr). We present brain MR examinations of seven patients with ADSL deficiency
      in the correlation with their clinical findings. In all cases lack of myelination
      or of delayed myelination of cerebral white matter was seen. Additionally
      cerebral and cerebellar atrophy was observed. Neuropathological findings revealed
      damage of all cellular elements of brain tissue and are cause of observed MR
      changes. Hypo/dysmyelination seemed to be secondary to damage of oligodendroglia
      and axons of damaged neuronal cells.

PMID- 20054784
TI  - Systemic administration of lipopolysaccharide impairs glutathione redox state and
      object recognition in male mice. The effect of PARP-1 inhibitor.
AB  - Our previous data demonstrated that systemic inflammation evoked by
      intraperitoneal injection of lipopolysaccharide (LPS; 1 mg/kg b.w.) induces
      morphological and biochemical changes in the brain, including alterations of
      poly(ADP-ribose) polymerase-1 (PARP-1) activity and expression of several genes.
      In this study, the effect of systemic inflammatory response (SIR) on glutathione
      redox state and on cognition, spatial memory and locomotor activity was evaluated
      by using spectrophotometric method, object recognition test, Morris water-maze
      and open-field tests, respectively. The effect of PARP-1 inhibitor was included
      in this study. Our data indicated that SIR significantly decreases reduced
      glutathione (GSH) level, enhances its disulfide form (GSSG) and decreases
      glutathione reductase activity. Moreover, SIR affects the object recognition and
      locomotor activity but has negligible effect on spatial memory. PARP-1 inhibitor
      protects against LPS-evoked recognition impairment and significantly improves
      spatial memory in LPS-treated mice. The effect of PARP-1 inhibitor could be in
      part connected with lowering of PARP-1 involvement in regulation of transcription
      of several pro-inflammatory genes. Moreover, PARP-1 inhibitors may modulate
      glutamatergic receptor signaling that plays an important role in learning and
      memory.

PMID- 20054785
TI  - Alterations in glutamate transport and group I metabotropic glutamate receptors
      in the rat brain during acute phase of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics
      many aspects of multiple sclerosis (MS). In MS the immune system attacks the
      white matter of the brain and spinal cord, leading to disability and paralysis.
      Neurons, oligodendrocytes and myelin are lost due to the release of cytotoxic
      cytokines, autoantibodies and toxic amounts of the excitatory neurotransmitter
      glutamate. This study was designed to determine the changes in: a) glutamate
      transport in nerve endings and astroglial fraction, b) level of excitatory amino
      acid transporters (EAATs) and c) level of group I metabotropic glutamate
      receptors (mGluR G I) protein in the acute phase of EAE (12 d.p.i. - day post
      immunization), in the peak of neurological deficits. We have found that glutamate
      uptake in synaptosomes and GPV fraction increases by about 30% and 15%,
      respectively, compared to controls. We also observed an increase in KCl-dependent
      glutamate release from synaptosomes and GPV fraction obtained from EAE rats by
      about 20%. Western blots analysis of protein expression shows elevation of group
      I metabotropic glutamate receptors (mGluR G I) and excitatory amino acid
      transporters (EAATs) in EAE rats during the acute phase of the disease (12
      d.p.i), when the level of proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha)
      rises. The results suggest that during the inflammatory conditions in the acute
      phase of EAE, disturbances in glutamate transport take place that may lead to the
      excitotoxicity.

PMID- 20054786
TI  - MMP2 and MMP9 in immature endothelial cells following surgical injury of rat
      cerebral cortex--a preliminary study.
AB  - Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of
      extracellular matrix remodeling. They have been implicated in various
      physiological and pathological phenomena involving neurovascular unit elements
      (neurons, astrocytes and capillary vessels). Surgical injury of the fronto
      temporal region of rat cerebral cortex induces massive neurodegeneration and cell
      death accompanied by astrogliosis. In the area adjacent to the damage, the
      induction of angiogenesis is observed, in which process immature endothelial
      cells are important players. The aim of this study was to examine the expression
      of MMP2 and MMP9 in cortical blood vessels following the surgical injury of
      cerebral cortex in the rat. Our data demonstrated absence of immature endothelial
      cells and lack of or only weak MMP2 and MMP9 immunoreactivities in some cortical
      capillaries in intact rats. Following the surgery, we found high MMPs'
      immunoreactivities in walls of the vessels located in the cortex adjacent to the
      lesion site, and particularly in the immature endothelial cells. These results
      show for the first time the presence of MMPs in the immature (progenitor?)
      endothelial cells following surgical brain injury..

PMID- 20054787
TI  - The evaluation of the influence of a high injury to brachial plexus elements on
      the condition of neurons of the anterior horns of the spinal cord--experimental
      research.
AB  - The aim of the experimental research was to assess the impact of a high damage to
      brachial plexus elements on the condition of neurons of spinal cord anterior
      horns. The research was conducted on 12 rabbits, in which the ventral branches of
      spinal nerves C5-Th1 were severed. During dissections carried out 7, 30, 60, 180
      days after the operation the cervicothoracic segment of the spinal cord was
      collected. The material was subjected to microscopic histological and
      ultrastructural examinations, which showed that where brachial plexus elements
      had been severed some of the neurons of spinal cord anterior horns had died and
      that the process intensity depended on the time that had passed after the injury.

PMID- 20054788
TI  - Papillary ependymoma with unique superficial cortical location:
      immunohistochemical and ultrastructural studies. A case report.
AB  - Ependymomas are relatively rare neoplasms of the central nervous system that
      typically develop along cerebral ventricles and central canal of spinal cord.
      Occasionally, the tumours of ependymal origin arise supratentorially in brain
      parenchyma as ectopic cortical mass without any connection to the ventricular
      system. Ependymomas are heterogeneous group of tumours including cellular,
      papillary, clear cell and tanacytic histology. The papillary ependymoma is an
      unusual variant of ependymoma characterized by distinct morphology resembling
      other papillary tumours and corresponding to WHO grade II malignancy. We present
      an unique case of ependymoma with distinctive papillary morphology at ectopic
      superficial cortical localization. The tumour occurred in eleven-years-old girl
      as a large, well-circumscribed mass in the left parietal lobe without continuity
      with the ventricular system. The patient presented with severe headache, vomiting
      and sudden-onset right hemiparesis. Histopathologically, the tumour revealed
      distinct papillary pattern with numerous pseudorosettes. Immunohistochemically,
      the neoplastic cells of both papillary structures and pseudorosettes were
      positive for glial fibrillary acidic protein and vimentin, whereas they were only
      slightly immunoreactive for epithelial membrane antigen and negative for
      cytokeratins. Ultrastructural findings revealed the presence of cilia usually
      located in the neoplastic cell bodies and intermediate glial-like filaments. The
      final diagnosis of papillary ependymoma at ectopic superficial localization was
      based on both, immunophenotypic profile and ultrastructural features that
      confirmed ependymal nature of neoplastic cells.

PMID- 20054789
TI  - Ten years observation and treatment of multifocal pilocytic astrocytoma.
AB  - Pilocytic astrocytoma (PA) usually occurs in younger patients. It is a benign,
      generally well-delineated, WHO grade I tumour with favorable prognosis, which
      makes it different from diffuse astrocytomas, classified as higher grades of
      malignancy. A case study of PA was presented in a young female patient, observed
      and treated at the Neurosurgical Department for the period of 10 years, during
      which time she had frequent surgical procedures due to recurrence and
      dissemination of the tumour. The initial symptom of the disease was epileptic
      seizure at the age of 16. Neuroradiological study revealed cerebral tumour in the
      right temporal lobe, then the first temporal lobe surgery followed by re
      operation and radiotherapy was performed. The patient developed hydrocephalus,
      treated with the ventriculo-peritoneal shunt. After 5 years local recurrence of
      the tumour appeared in the right temporal region. The patient was operated and
      the tumour was totally removed. Initially, the histopathological diagnosis of
      ganglioglioma was suggested for primary tumour, finally the diagnosis of
      pilocytic astrocytoma for both recurrent and primary tumour was established.
      During the next years of observation increasing neurological symptoms in lower
      limbs developed. Subsequently, the patient reported pain syndrome in lumbosacral
      and perineal area. Consecutive MRI studies revealed a spinal canal tumours
      localized at the thoracic level and next at sacral level. The spinal tumour was
      surgically treated in both locations; the last operation was done 10 years after
      surgery of the primary temporal lobe tumour. Histopathological examinations of
      the excised foci from spinal canal revealed neoplasm consistent with WHO grade I
      pilocytic astrocytoma. The presented case indicates that despite the spread of
      the neoplastic process, a histopathologically benign tumour (WHO I grade) allows
      for long-term survival and observation period. Unfortunately, multifocal tumour
      involving midline structures causes major neurological symptoms and deficits. In
      the presented case we dealt now with the ascending spread process and the
      occurrence of the new foci in both subtentorial and parameningeal spaces inside
      the cranial cavity. It is a rare clinical manifestation of a disease ever
      described in the literature.

PMID- 20054790
TI  - Malformations of the brain in two fetuses with a compound heterozygosity for two
      PAX6 mutations.
AB  - PPAX6 is an important transcription factor which plays an essential role in brain
      morphogenesis and eye development. It is related to migration of neuroblasts to
      the cerebral cortex and deep telencephalic nuclei, and the specification of
      cellular and regional identity. Disturbances of brain development in two sib
      fetuses whose parents were aniridic (both sporadic cases) are reported. Molecular
      analysis in both parents has shown different mutations in PAX6 gene and a
      compound heterozygosity for two PAX6 mutations in both fetuses.
      Neuropathologically both cases showed severe brain malformations with increased
      germinal proliferation, gross disturbances of migration and organization of the
      CNS.

PMID- 20054791
TI  - [Scientific research in general psychiatric hospitals].

PMID- 20054792
TI  - [The journal in 2009].

PMID- 20054793
TI  - [Personality traits of patients who have recovered completely from depression].
AB  - BACKGROUND:  BACKGROUND: The psychobiological model of personality developed by
      Cloninger includes four dimensions of temperament and three dimensions of
      character. Studies have indicated that the personality dimensions of patients
      with depression differ from those of control subjects without depression. AIM: To
      assess whether the personality traits of persons who have experienced one or more
      depressive episodes in the past and have made full recovery differ from the
      personality traits of persons who have never suffered from depression. METHOD:
      The personality dimensions for 40 persons in remission but with a previous
      history of depression and for 49 healthy controls were determined by means of a
      Dutch version of the Temperament and Character Inventory (tci) questionnaire.
      results Compared to the control subjects, patients in remission showed a
      significant increase on the temperament scale Harm Avoidance and a statistically
      significant decrease on the character scale Self-Directedness. The increase also
      applied to all subscales of Harm Avoidance and the decrease applied to four of
      the five subscales of Self-Directedness. CONCLUSION: Compared to healthy control
      subjects, patients in remission showed a distinctly different personality
      profile. None of these differences can therefore be regarded merely as a
      transient phenomenon during a depressive episode ('state effect'). However, it
      cannot be concluded from the current study whether the altered personality
      profile is a consequence of having had a depression or whether it is a 'scarring
      effect' of a pre-existing vulnerability factor.

PMID- 20054794
TI  - [Drop-out from clinical psychotherapeutic treatment of personality problems].
AB  - BACKGROUND: Drop-out is a serious problem in psychotherapy. Earlier studies have
      shown that the main factors associated with drop-out are young age, low socio
      economic status and pathological symptoms such as severity of the problems and
      problematic substance-abuse. AIM: To investigate patient's and pathological
      characteristics that predict drop-out among patients with predominantly
      personality problems. METHOD: Patient's characteristics and pathological
      characteristics of 372 subjects were ascertained via a retrospective study by
      means of four databases: intake letters, scid-ii personality questionnaires, scid
      i and ii interviews and discharge letters. The association between these
      characteristics and drop-out was tested by means of bivariate and multivariate
      analysis. results The drop-out rate was 33.3 %. The main predictors of drop-out
      were young age, a low Global Assessment of Functioning (gaf)-score and the
      existence of problematic substance-abuse at discharge. The degree and severity of
      axis i disorders and the nature of personality problems made hardly any
      contribution to the prediction of drop-out. CONCLUSION: These findings indicate
      that more attention needs to be given to the existence of substance-abuse before
      psychotherapy begins. Drop-out is still a problem and is difficult to predict and
      hard to influence.

PMID- 20054795
TI  - [Compulsive buying or oniomania: an overview].
AB  - BACKGROUND: Compulsive buyers feel a continual urge to buy things, irrespective
      of their financial means. Interest in compulsive buying has increased in the last
      30 to 40 years. Since excessive buying is a regularly occurring feature of
      various illnesses encountered in clinical practice, one wonders whether it should
      be regarded as a sign of the times, as a symptom of a psychiatric illness or as a
      distinct psychiatric syndrome. AIM: To gain insight into the concept of
      compulsive buying. METHOD: We searched the literature via Medline, PubMed and
      PsycInfo for the period from 1966 to August 2008. results Compulsive buying is a
      relatively unknown and poorly defined phenomenon, despite its high incidence and
      high comorbidity. It is characterised by chronic, repetetive behaviour; it occurs
      mainly among women and should be classified as an impulsive-control disorder nos.
      Current aetiological models lack explanatory power and, so far, the most
      successful treatment results seem to have been achieved with behavioural therapy.
      CONCLUSION: Compulsive buying should be considered from a neuroscientific
      perspective. Future research needs to have a neuropsychiatric focus and a
      contextual psychological and behavioural analytical approach in which inhibition,
      self-control and rule-governed behaviour play a central role.

PMID- 20054796
TI  - [Neurofeedback and attention deficit hyperactivity disorder: what is it and is it
      working?].
AB  - BACKGROUND Neurofeedback (nf) is a method of treatment that is being used
      increasingly in the Netherlands, particularly in psychological practices. Many
      psychiatric and somatic symptoms are currently being treated with the help of nf.
      In particular, nf is being used more and more to treat attention deficit
      hyperactivity disorder (adhd). Despite its growing popularity, nf is still a
      relatively unknown treatment method in psychiatric practices. AIM: To investigate
      the scientific evidence for treating adhd with nf. METHOD: We searched the
      literature for reports on controlled trials that investigated the effectiveness
      of nf on adhd. results Six controlled trials were located. The studies reported
      that nf had a positive effect on adhd, but all the studies were marred by
      methodological shortcomings. CONCLUSION: On the basis of currently available
      research results, no firm conclusion can be drawn about the effectiveness of
      treating adhd by means of nf. In view of the fact that nf is being used more and
      more as a method of treatment, there is an urgent need for scientific research in
      this field to be well planned and carefully executed.

PMID- 20054797
TI  - [Psychiatric disorders in velo-cardio-facial syndrome].
AB  - Velo-cardio-facial syndrome (vcfs) is a congenital disorder with a markedly
      variable clinical expression. The majority of those affected have cognitive
      behavioural symptoms and psychiatric problems. Most of the somatic
      characteristics can be treated effectively. The quality of life of patients with
      vcfs is therefore determined largely by cognitive and behavioural symptoms,
      including the increased risk of psychiatric disorders. On the basis of a case
      study featuring a 41-year-old vcfs patient and by reviewing the literature we
      describe the psychiatric disorders that can occur in conjunction with this
      syndrome.

PMID- 20054798
TI  - [Antipsychotic agents and stimulants: a judicious combination?].
AB  - A 31-year-old male, diagnosed with schizophrenia and receiving maintenance
      treatment with olanzapine, was prescribed methylphenidate for comorbid attention
      deficit hyperactivity disorder (adhd). The adhd symptoms diminished and there
      were hardly any side-effects. No increase in psychotic symptoms occurred. The
      patient used far fewer amphetamines and benzodiazepines. In theory, stimulants
      and antipsychotics produce opposite effects. Relevant literature on the subject
      is discussed.

PMID- 20054799
TI  - Chronic morpho-functional damage as a consequence of transient
      ischemia/reperfusion injury of the small bowel.
AB  - INTRODUCTION: The prevailing notion is that ischemia reperfusion injury of the
      small bowel induces transient changes that resolve within a few days post
      occurrence. However, chronic injury has been described following a single
      ischemia reperfusion in the kidney. We proceeded to ascertain if a similar
      outcome is also witnessed in the small bowel. MATERIALS AND METHODS: ACI rats
      (n=32) underwent 1, 2 or 3 episodes of ischemia reperfusion by clamping the
      superior mesenteric artery for 45 minutes at 7-day intervals. Control groups
      included sham-operated (n=6) or non-operated (n=5) rats. Morphology was examined
      at day ninety post-ischemia reperfusion and immunostaining was used to evaluate
      macrophage infiltration, microvascular distribution, and apoptosis. RT-PCR was
      used to evaluate expression of Inter-Cellular Adhesion Molecule-1 (ICAM-1),
      transforming growth factor-beta (TGF-beta), Insulin Growth Factor-I (IGF-1), and
      Insulin Growth Factor-I Receptor (IGF-R). Intestinal function was evaluated by D
      xylose performed 24 hours and 4, 8, and 12 weeks after reperfusion. RESULTS:
      Chronic morphologic changes were observed with degeneration of crypts,
      endothelial damage, matrix degeneration, and heightened lymphocyte degeneration
      within the Payer's patches. Major structural changes were characterized by
      villous atrophy from partial to total. The grade of histological injuries was
      significantly increased (P<0.001) after multiple ischemia reperfusion episodes. A
      higher number of apoptotic cells (P<0.001) and a prominent macrophage
      infiltration (P<0.05) was also witnessed. Altered expression of ICAM-1, TGF-beta,
      and IGF-1 was observed. At 24 hours after ischemia reperfusion D-xylose
      absorption was diminished, returning to baseline values within 4 weeks and
      becoming abnormal again at 8 and 12 weeks (P<0.05). CONCLUSIONS: Unlike the
      prevailing conviction, these data demonstrate that transient ischemia reperfusion
      repeated injuries of the small bowel result in chronic intestinal damage.

PMID- 20054800
TI  - P21, p27, bax, cathepsin and survivin pathways in macular dystrophy corneas.
AB  - The purpose of our study was to elucidate pathways of genetically programmed cell
      death (apoptosis) in corneas with macular dystrophy. 10 corneal buttons (10
      patients) with macular dystrophy and 8 buttons (8 patients) from enucleated eyes
      with chorioideal melanoma (controls) were analysed histologically.
      Immunohistochemical analysis was performed to investigate the presence of p21,
      p27, bax, cathepsin and survivin proteins. The number of positive cells was
      determined by analysis of 100 cells and given in percentages. The bax protein was
      present in 25.6% of epithelial cells in macular dystrophy corneas but was absent
      in controls. P21 and p27 were found in 35.7 and 87.5% of epithelial cells of
      macular dystrophy corneas, respectively, but again not in control tissue. In
      contrast, a lower percentage of cathepsin-positive (30.7% vs 58.8%) and survivin
      positive cells (37.6% vs 52.1%) were present in epithelial cells of macular
      dystrophy corneas than in control epithelial cells. The difference reached
      statistical significance in the expression of p21 and p27 genes (p<0.05 in both).
      P21 was positive in 3% of keratocytes, p27 in 1% of endothelial cells of macular
      dystrophy corneas but negative in controls (0%). Bax, cathepsin and survivin
      immunopositivity was not detected in keratocytes or endothelial cells of either
      group. We conclude that the down-regulation of p21, p27 and cathepsin in
      epithelial cells of macular dystrophy corneas may be related to defense
      mechanisms against apoptotic cell death.

PMID- 20054801
TI  - Histological scoring of articular cartilage alone provides an incomplete picture
      of osteoarthritic disease progression.
AB  - PURPOSE: To ascertain whether molecular subcategories of disease progression
      exist within established histological grades of articular cartilage (AC).
      METHODS: Based on H&E and safranin-O staining of AC sections obtained from 18
      knee arthroplasty surgeries, 30 samples ranging from Mankin Scoring System grade
      1 through 5 were identified. Immunohistochemical (IHC) analysis for collagen type
      II and aggrecan was performed on serial sections of the paraffin-embedded AC
      samples. Six AC samples from each of the five Mankin Scoring System grades were
      examined. RESULTS: Significant IHC differences in collagen type II and aggrecan
      deposition were seen within AC samples from all five histological grades. The
      range of IHC differences in collagen type II and aggrecan increased with
      increasing histological grade. A change in the pattern of collagen type II
      deposition was observed in MG-3 AC that was consistent with a switch in collagen
      type II metabolism. CONCLUSIONS: IHC staining of collagen type II and aggrecan
      can identify differences within histological grades of AC that are consistent
      with the existence of molecular subcategories. These differences were detectable
      even within the lowest histological grades; therefore the use of IHC staining can
      further enhance and refine the scoring of AC deterioration in early
      osteoarthritis (OA). Furthermore, the changes seen in the deposition pattern for
      both aggrecan and collagen type II suggest that they could be used to monitor key
      molecular events in OA progression. These findings also underscore the need for
      the development of IHC scoring criteria.

PMID- 20054802
TI  - Survivin overexpression in HCC and liver cirrhosis differentially correlates with
      p-STAT3 and E-cadherin.
AB  - Survivin, a member of the family of inhibitor of apoptosis proteins, functions as
      a key regulator of apoptosis and cell proliferation. Overexpression of survivin
      has been implicated in several human cancers, including human hepatocellular
      carcinoma (HCC). Although several factors have been shown in vitro to upregulate
      survivin expression in cancer cells, the in vivo regulators of survivin in human
      hepato-carcinogenesis are largely unknown. We studied by immunohistochemistry the
      protein expression of survivin in relation to cyclin D1, phosphorylated signal
      transducer and activator of transcription 3 (p-STAT3), beta-catenin, E-cadherin
      and phosphorylated-Akt (p-Akt) in 69 cases of HCC and adjacent liver cirrhosis.
      Survivin was expressed in 63/69 (91.3%) cases of HCC and in 40/47 (85.1%) cases
      of liver cirrhosis. Survivin localization in HCC was exclusively nuclear, while
      intense cytoplasmic and low nuclear expression of survivin was observed in cases
      of cirrhosis. Survivin expression in HCC correlated significantly with low grade
      tumors, expression of cyclin D1 and p-STAT3. Expression of survivin in liver
      cirrhosis correlated with downregulation of E-cadherin expression. There was no
      significant correlation of survivin with beta-catenin or p-Akt in HCC or liver
      cirrhosis. In conclusion, we showed an association of nuclear survivin with well
      differentiated HCC, as well as with the expression of the cell cycle regulator
      cyclin D1. Activation of STAT3 and loss of E-cadherin but not beta-catenin or Akt
      pathways seem to be implicated in survivin upregulation in HCC and liver
      cirrhosis.

PMID- 20054803
TI  - Comparison of the tumorigenic potential of liver and kidney tumors induced by N
      nitrosodimethylamine.
AB  - The aim of the study was to determine the tumorigenic potential of two cell lines
      established from N-nitrosodimethylamine induced rat hepatocarcinoma (HeDe) and
      mesenchymal renal tumors (NeDe). The basis of the distinction is that human
      cancers are known to overexpress facilitative GLUT transporters and TGF-beta1
      protein. These proteins are linked to the increased metabolic energy consumption
      indicating uncontrolled growth and proliferation. We have assayed not only the
      expression of GLUT-1, GLUT-3 and TGF-beta1 proteins, but also the uptake of 2
      fluoro-[18F]-2-deoxy-D-glucose (18FDG), a tracer for cancer diagnosis. Western
      blot analysis and whole body autoradiography were used to measure the 18FDG
      uptake of tumor cells. Elevated 18FDG uptake was measured in both tumor cell
      lines. Whole body autoradiography provided evidence that the uptake of 18FDG was
      lower in the necrotic inner part than in the more vascularized outer parts of
      primary hepatocarcinoma and mesenchymal renal tumors. GLUT-1 overexpression in
      hepatocarcinoma tumor, and high levels of GLUT-3 were found in the NeDe cell line
      and in the mesenchymal renal tumor. TGF-beta-1 was overexpressed in
      hepatocarcinoma and mesenchymal renal tumors. In vitro and in vivo parameters
      support the view that the tumorigenic potential of cancer cells cannot be
      determined by the expression of a single parameter such as the expression of
      either GLUT-1, GLUT-3 or 18FDG uptake. Besides the tumorigenic potential of the
      hepatocarcinoma, the high metabolic activity of the renal tumor indicated by its
      18FDG uptake, GLUT-3 and TGF-beta1 expression, the mesenchymal renal tumor
      induced by N-nitroso-dimethylamine is not a benign, but an an aggressive renal
      carcinoma.

PMID- 20054804
TI  - Carbonic anhydrase II is secreted from bovine parotid glands.
AB  - Besides carbonic anhydrase VI (CA-VI), CA-II is suggested to be a second secreted
      isoenzyme in ruminant saliva. Therefore, the aim of the present study was to
      investigate the expression of salivary CA-II in bovine parotid glands at the
      protein level. Moreover, we intended to identify the cells which secrete the
      enzyme into the saliva. Two commercially available CA-II specific antibodies were
      tested for use in immunohistochemistry on frozen sections of bovine parotid
      tissue. Intense positive staining for CA-II was found in luminal duct cells and
      for the first time also inside the duct lumen, clearly demonstrating the
      expression and secretion of salivary CA-II in bovine parotid glands. The presence
      of CA-II protein was verified for parotid tissue and whole saliva using
      immunoblot analysis. Both salivary CA-II and CA-VI are highly active in supplying
      the alimentary tract with bicarbonate. It is suggested that a decrease in the
      expression of either one of these enzymes might severely disturb digestion and/or
      increase susceptibility to acidosis in ruminants.

PMID- 20054805
TI  - Expression of p53 family members and CD44 in oral squamous cell carcinoma (OSCC)
      in relation to tumorigenesis.
AB  - Oral squamous cell carcinomas (OSCCs) are described as the result of a multistep
      tumorigenesis process. In order to develop useful diagnosis of pre-malignant
      lesions, expression of p53 family members and the cancer stem cell (CSCs) marker,
      CD44v6, were studied in histologically normal oral epithelium, precancerous
      lesions and succeeding invasive OSCCs. p53 was expressed focally in normal
      epithelium adjacent to tumors, while expression was high in intra-epithelial
      neoplasia and moderate in OSCC. p63 nuclear staining was important in basal and
      suprabasal layers of histologically normal oral mucosa and in immature
      compartments of premalignant lesions and cancer. In epithelium without neoplasia,
      intense p73 staining was observed in the basal layer, while focal expression was
      present in suprabasal layers. Most immature dysplastic areas showed either high
      or moderate staining, whereas those in OSCCs expressed low and moderate p73 level
      expression. CD44v6 was only expressed in poorly differentiated areas of
      epithelium, altered or not. p53, p63 and p73 positive stainings were
      statistically related in intra-epithelial neoplasia to tumours. Analysis of TP53
      mutations in 17% of tumours principally revealed G>A and A>G transitions. No
      relation was observed between this mutational profile and different
      immunostainings. In conclusion, our results support that immunostaining of p53
      family members might be helpful in diagnosis and monitoring of high-risk pre
      malignant lesions of oral epithelium. The combination of staining patterns of
      p63, p73alpha and CD44v6 enabled us to isolate phenotypic undifferentiated or
      transient amplifying areas, reflecting the immaturity of the tumour cell lineage.
      While CD44v6 expression is an interesting marker of such epithelial cells, it is
      not specific enough to be useful alone and other phenotypic markers are needed.

PMID- 20054806
TI  - Clinicopathological variables, immunophenotype, chromosome 1p36 loss and tumour
      recurrence of 247 meningiomas grade I and II.
AB  - The WHO grading scheme distinguishes benign (grade I), atypical (grade II) and
      anaplastic (grade III) meningiomas. Both atypical and anaplastic meningiomas
      exhibited an overall increased rate of recurrence, but between 15-20% benign
      meningiomas will also exhibit an unfavourable clinical course with recurrence
      before 10 years despite aggressive surgery. We investigated 247 cases of
      meningiomas grade I and II. The immunohistochemical expression of 30 different
      molecular biomarkers of cell adhesion molecules, cell-cycle and apoptosis
      regulators and checkpoints was analyzed. We also determined apoptosis by in-situ
      hybridization (APOPDETEKTM) and loss of chromosome 1p36 by FISH. The study
      revealed a statistically significant co-variation (p<0.05) between meningiomas
      grade II associated with several clinicopathological features (Simpson grade of
      clinical resection, necrosis, nuclear atypia, macronucleoli, transition to small
      cell, sheet-like growth, high cellularity), increased expression of several
      biomarkers of tumour proliferation (Cyclin A, Cyclin E, MIB-1 or MDM2), proteases
      (Cathepsin D) or cell-adhesion (CD44) and lower expression of progesterone
      receptors than meningiomas grade I. The presence of Psammoma bodies or the
      location at convexity were protective prognostic factors for tumour recurrence
      while high cellularity and early age of onset (<57 year-old) were indicators of
      increased recurrence risk. The expression of COX-2, gamma-catenin, Topoisomerase
      IIa, VEGF and MIB-1 was significantly higher in the cohort of recurrent
      meningiomas. Meningiomas with chromosome 1p36 loss showed a higher recurrence
      rate (33.3%) than meningiomas with normal chromosome 1p36 (18%). Increased COX-2
      expression in recurrent meningioma may also suggest a putative role of COX-2
      inhibitors as a chemopreventive treatment for recurrence.

PMID- 20054807
TI  - MCM proteins as diagnostic and prognostic tumor markers in the clinical setting.
AB  - Minichromosome maintenance (MCM) proteins are essential for the process of DNA
      replication, functioning as license components for the S-phase of cell-cycle
      initiation and further exerting weak helicase activity to unwind DNA from its
      supercoiled state at replication forks. The requirement for MCM proteins in
      cycling cells and their absence in quiescent ones supports evidence for their
      potential clinical application as cell proliferation markers. In the last few
      years, aside from their utility as cell proliferation markers, the assessment of
      MCM expression levels in diverse human malignancies has been the focus of
      extensive research in an aim to facilitate tumor diagnosis and prognosis in
      clinical settings. The present article aims to review the available data so far
      concerning the clinical significance of MCM protein expression in human neoplasia
      in comparison to conventional proliferative markers. A review of the literature
      revealed that MCM expression is associated with important clinicopathological
      parameters for patient management and also exhibits significant diagnostic and
      prognostic value in several malignancies. MCMs are characterized by higher
      specificity and sensitivity than the conventional proliferative markers, such as
      Ki-67 and PCNA, and are thus considered as diagnostic and prognostic tools of
      greater clinical significance in several types of human malignancy.

PMID- 20054808
TI  - Stem cells in human breast cancer.
AB  - Increasing data support cancer as a stem cell-based disease. Cancer stem cells
      (CSCs) have been found in different human cancers, and recent evidence indicates
      that breast cancer originates from and is maintained by its own CSCs, as well as
      the normal mammary gland. Mammary stem cells and breast CSCs have been identified
      and purified in in vitro culture systems, transplantation assays and/or by cell
      surface antigen identification. Cell surface markers enable the functional
      isolation of stem cells that can initiate and propagate tumorigenesis in mammary
      gland. These observations have dramatic biological and clinical significance due
      to increasing evidence suggesting that the recurrence of human cancer and
      treatment failure may reflect the intrinsic quiescence and drug resistance of
      CSCs. Thus, the CSC hypothesis provides fundamental implications for
      understanding breast carcinogenesis and for developing new strategies for breast
      cancer prevention and therapy for advanced disease. Further strategies to isolate
      breast CSCs, to find additional trustworthy surface markers, and to compare gene
      expression pathways profiles with their normal stem cells counterparts are
      necessary to more accurately define putative breast cell-lineage markers for the
      different cell types present in the mature mammary gland and to identify
      potential therapeutical targets in breast cancer. This review discusses the
      current knowledge about stem cells and CSCs, focusing on mammary stem cells and
      breast CSCs, and their consequences for breast tumorigenesis and implications for
      breast cancer susceptibility, prognosis, and treatment.

PMID- 20054809
TI  - Angiopoietin-1/Tie2 receptor signaling in vascular quiescence and angiogenesis.
AB  - Angiopoietin (Ang) 1 is a ligand for endothelium-specific receptor tyrosine
      kinase Tie-2. In adult vasculature, Ang1/Tie2 signaling is thought to regulate
      both maintenance of vascular quiescence and promotion of angiogenesis. However,
      it has been unknown how Tie2 signal regulates these distinct biological
      functions. Recently, we and Alitalo's group have clarified that Ang1 assembles
      distinct Tie2 signaling complexes in either presence or absence of endothelial
      cell-cell adhesions. Ang1 induces trans-association of Tie2 at cell-cell
      contacts, whereas Tie2 is anchored to the extracellular matrix (ECM) by Ang1 at
      the cell-substratum interface. Trans-associated Tie2 and ECM-anchored Tie2
      activate distinct signaling pathways. In this review, we discuss how Ang1/Tie2
      signal regulates both maintenance of vascular quiescence and promotion of
      angiogenesis, especially focusing on the roles of trans-associated Tie2 and ECM
      anchored Tie2.

PMID- 20054810
TI  - The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated
      transfer of genetic information.
AB  - It has been commonly supposed that adult stem cells co-localize with supporting
      cells within specific regions or specialized microenvironment in each
      tissue/organ, called stem cell niche. This concept was based on the assumption
      that stem cells are intrinsically hierarchical in nature. However, recent data
      indicate that stem cells may represent a continuum with reversible alterations in
      phenotype taking place during the transit through cell cycle. Based on this
      dynamic interpretation it has been suggested that the so-called niche is
      represented by a single or only few cell types continually adjusting their
      phenotype and function to individual circumstances. A critical component in the
      regulation of the continuum of stem cell phenotypes is the microenvironment. In
      this context, microvesicles (MVs) account for the transfer of genetic information
      between cells. Originally considered inert cellular debris, MVs are increasingly
      recognized to be important mediators of cell-to-cell communication. MVs may
      transfer receptors, proteins, mRNA and microRNA to target cells via specific
      receptor-mediated interaction. In stem cell biology the exchange of genetic
      information may be bidirectional from stromal to stem cells. In the context of
      tissue injury the MV-mediated transfer of genetic information may reprogram the
      phenotype of stem cells to acquire features of the injured tissue cells. In
      addition, MVs derived from stem cells may induce de-differentiation of cells
      which have survived injury with a cell cycle re-entry that may allow tissue
      regeneration. In the present review we discuss the possibility of a continuous
      genetic modulation of stem cells by a MV-mediated transfer of information between
      cells.

PMID- 20054811
TI  - Transcriptional regulation of the Oct4 gene, a master gene for pluripotency.
AB  - Oct4 is one of the most important transcription factors required to maintain an
      undifferentiated state (self-renewal) and pluripotency of human and mouse
      embryonic stem (ES) cells as well as early embryonic cells. In addition, Oct4 is
      the only known transcription factor that has to be exogenously introduced into
      differentiated cells to make induced pluripotent stem (iPS) cells. Therefore, it
      is of great importance to understand how Oct4 transcription is regulated in ES
      cells and embryos and how it becomes activated during iPS cell formation. In this
      article, we will review the regulation of the mouse Oct4 gene from the viewpoint
      of DNA methylation, binding of orphan nuclear receptors, histone modifications
      and synergistic effects with other pluripotency factors. We will also raise
      several key questions that need to be addressed in future work to improve our
      understanding of Oct4 gene regulation and its essential role in self-renewal and
      pluripotency.

PMID- 20054812
TI  - Cholinergic activation of hippocampal neural stem cells in aged dentate gyrus.
AB  - Adult hippocampal neurogenesis contributes to the hippocampal circuit's role in
      cognitive functioning. New neurons are generated from hippocampal neural stem
      cells (NSCs) throughout life, but their generation is substantially diminished in
      aged animals due to a decrease in NSC proliferation. Because acetylcholine (ACh)
      is an important neurotransmitter released in the hippocampus during learning and
      exercise that is known to decrease with aging, we investigated whether aged NSCs
      can respond to ACh. In this study, we found that cholinergic stimulation has a
      positive effect on NSC proliferation in both young adult (8-12 weeks old) and
      aged mice (>2 years old). In fresh hippocampal slices, we observed a rapid
      calcium increase in NSCs in the dentate gyrus after muscarinic cholinergic
      stimulation, in both age groups. Furthermore, we found that the exercise-induced
      promotion of aged NSC proliferation was abrogated by the specific lesioning of
      the septal cholinergic system. In turn, cholinergic activation by either eserine
      (physostigmine) or donepezil treatment promoted the proliferation of NSCs in aged
      mice. These results indicate that NSCs respond to cholinergic stimulation by
      proliferating in aged animals. Physiological and/or pharmacological cholinergic
      stimulation(s) may ameliorate cognitive decline in aged animals, by supporting
      adult hippocampal neurogenesis.

PMID- 20054813
TI  - Cardiovascular diseases and hippocampal infarcts.
AB  - The prevalence of hippocampal lesions such as hippocampal infarcts have not been
      studied in detail even though hippocampal alterations are known to be associated
      with various clinical conditions such as age-related degenerative disorders and
      epilepsy. METHODS: Here we defined the hippocampal infarcts and assessed the
      prevalence of this lesion in large unselected population of 1,245 subjects age
      ranging from 1 to 99 years (mean age 79 +/- 1 S.E.M). Furthermore, we assessed
      the association of these lesions with various cardio- and cerebro-vascular
      disorders and other neurodegenerative lesions. The prevalence of hippocampal
      infarct in the study population of 1,245 subjects was 12%, increasing to 13% when
      only those with a clinically diagnosed cognitive impairment (n = 311) were
      analyzed. Large hemispheric brain infarcts were seen in 31% of the study subjects
      and these lesions were strongly associated with cardiovascular risk factors such
      as hypertension (43%), coronary disease (32%), myocardial infarct (22%), atrial
      fibrillation (20%), and heart failure (20%). In contrast, hippocampal infarcts
      displayed a significant association only with large hemispheric brain infarct,
      heart failure, and cardiovascular index as assessed postmortem. It is noteworthy
      that only widespread hippocampal infarcts were associated with clinical symptoms
      of cognitive impairment or epilepsy. The surprisingly low prevalence of 12% of
      hippocampal infarcts in aged population found here and the failure to detect an
      association between this lesion and various cerebro- cardio-vascular lesions is
      intriguing. Whether susceptibility to ischemia in line with susceptibility to
      neuronal degeneration in this region is influenced by still undetermined risk-
      factors need further investigation. Furthermore it should be noted that the size
      of the hippocampal tissue damage, i.e., small vs. large cystic infarcts is of
      significance regarding clinical alterations.

PMID- 20054814
TI  - Adenosine modulates the excitability of layer II stellate neurons in entorhinal
      cortex through A1 receptors.
AB  - Stellate neurons in layer II entorhinal cortex (EC) provide the main output from
      the EC to the hippocampus. It is believed that adenosine plays a crucial role in
      neuronal excitability and synaptic transmission in the CNS, however, the function
      of adenosine in the EC is still elusive. Here, the data reported showed that
      adenosine hyperpolarized stellate neurons in a concentration-dependent manner,
      accompanied by a decrease in firing frequency. This effect corresponded to the
      inhibition of the hyperpolarization-activated, cation nonselective (HCN)
      channels. Surprisingly, the adenosine-induced inhibition was blocked by 3 MUM 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) receptor antagonists,
      but not by 10 MUM 3,7-dimethyl-1-propargylxanthine (DMPX), a selective A(2)
      receptor antagonists, indicating that activation of adenosine A(1) receptors were
      responsible for the direct inhibition. In addition, adenosine reduced the
      frequency but not the amplitude of miniature EPSCs and IPSCs, suggesting that the
      global depression of glutamatergic and GABAergic transmission is mediated by a
      decrease in glutamate and GABA release, respectively. Again the presynaptic site
      of action was mediated by adenosine A(1) receptors. Furthermore, inhibition of
      spontaneous glutamate and GABA release by adenosine A(1) receptor activation was
      mediated by voltage-dependent Ca(2+) channels and extracellular Ca(2+) .
      Therefore, these findings revealed direct and indirect mechanisms by which
      activation of adenosine A(1) receptors on the cell bodies of stellate neurons and
      on the presynaptic terminals could regulate the excitability of these neurons.

PMID- 20054816
TI  - Neural system interactions underlying human transitive inference.
AB  - Human problem solving relies on multiple strategies supported by dynamic neural
      network interactions. The transitive inference (TI) problem solving task can be
      accomplished by the extraction of relations among stimuli or by responding to
      reinforcement histories of items using associative learning. Relational and
      associative strategies are assumed to rely on the hippocampus and caudate
      nucleus, respectively; which compete to control behavior. However, we found that
      increased recruitment of both systems in TI is correlated with greater accuracy
      and awareness, and reduced associative responding to single items. Contrary to
      prior assumptions, the hippocampus and caudate interact cooperatively to
      facilitate successful TI. We suggest that the dynamics of the relationship
      between the hippocampus and caudate depends critically upon task demands.

PMID- 20054815
TI  - Cholesterol homeostasis markers are localized to mouse hippocampal pyramidal and
      granule layers.
AB  - Changes in brain cholesterol homeostasis are associated with multiple diseases,
      such as Alzheimer's and Huntington's; however, controversy persists as to whether
      adult neurons produce their own cholesterol, or if it is outsourced to
      astrocytes. To address this issue, we analyzed 25 genes most immediately involved
      in cholesterol homeostasis from in situ data provided by the Allen Brain Mouse
      Atlas. We compared the relative mRNA expression in the pyramidal and granule
      layers, populated with neurons, with the rest of the hippocampus which is
      populated with neuronal processes and glia. Comparing the expression of the
      individual genes to markers for neurons and astrocytes, we found that cholesterol
      homeostasis genes are preferentially targeted to neuronal layers. Therefore,
      changes in gene expression levels might affect neuronal populations directly.

PMID- 20054817
TI  - An investigation of the effects of hippocampal lesions in rats on pre- and
      postoperatively acquired spatial memory in a complex environment.
AB  - In previous work, we showed that adult rats that were reared socially for 3
      months in a complex (village) environment retained allocentric spatial memory for
      that environment following hippocampal lesions (Winocur et al., (2005) Nat
      Neurosci 8:273-275). In the present series of experiments, we showed that 3
      months of postoperative rearing did not confer the same benefits (Experiment 1),
      although hippocampal groups, with or without rearing experience, exhibited
      spatial learning after extensive training (Experiments 1 and 2). Experiment 3
      showed that as little as 2 weeks of preoperative rearing in the village was
      sufficient to retain acquired spatial memories after hippocampal lesions. Probe
      testing revealed that, although rats with hippocampal lesions exhibited
      remarkably good memory for preoperatively learned locations in the village, they
      were impaired when changes in task demands required flexible use of existing
      spatial representations. In a direct test of flexibility (Experiment 4),
      preoperatively reared rats were administered a blockedroutes task in the original
      learning environment, in which on designated trials, a barrier was placed across
      one of the direct paths to the goal compartment. On encountering the barrier,
      control rats consistently selected the next most direct route, whereas rats with
      hippocampal lesions, despite using spatial strategies, made more errors and took
      longer to find the goal. The present results confirm that allocentric spatial
      memories can survive hippocampal damage but they are schematic in nature and less
      cohesive than those associated with cognitive maps in intact brains. As well,
      there was evidence that, although different processes are involved in their
      formation, the schematic memories that were acquired preoperatively and survived
      hippocampal lesions are essentially the same as those laboriously formed
      postoperatively after extensive training.

PMID- 20054818
TI  - Methylation of a single intronic CpG mediates expression silencing of the PMP24
      gene in prostate cancer.
AB  - BACKGROUND: We previously demonstrated that a putative anti-tumor gene,
      peroxisomal membrane protein 4, 24 kDa (PMP24 or PXMP4), is silenced via DNA
      methylation of a CpG island in its 5' flanking region (5'-CGI) in prostate cancer
      (PCa) cells. METHODS: To identify demethylation hypersensitive site(s) in PMP24
      5'-CGI, PC-3 cells with methylated 5'-CGI were treated with a low-dose of 5-aza
      2'-deoxycytidine (5-aza-dC) just sufficient to reactivate gene expression,
      referred as the limited demethylation approach. Gel shift assays and promoter
      analyzes were performed to demonstrate the role of the hypersensitive site in
      PMP24 gene regulation. Transfection of a methylated oligonucleotide corresponding
      to the hypersensitive site was conducted to determine the effect of site-specific
      methylation on the gene expression. Bisulfite sequencing analysis was performed
      to reveal the methylation status of PMP24 promoter in cultured cells and
      microdissected samples. In situ hybridization was applied to determine expression
      positivity of PMP24 mRNA. RESULTS: A 5-aza-dC hypersensitive site encompasses two
      CpG dinucleotides in intron 1 was identified. Methylation of the first, but not
      the second, CpG dinucleotide of this site disrupted DNA-protein interactions and
      suppressed the gene expression. Using archival specimens, we found the first CpG
      dinucleotide of the hypersensitive site is hypermethylated with a loss of PMP24
      mRNA expression in microdissected PCa cells when compared to normal prostatic
      epithelial cells. CONCLUSIONS: These findings support a critical role for a
      single intronic CpG dinucleotide in PMP24 gene regulation through DNA
      methylation. The data suggest that methylation-mediated silencing of PMP24 is a
      molecular event associated with prostate carcinogenesis.

PMID- 20054819
TI  - Dystroglycan is not required for maintenance of the luminal epithelial basement
      membrane or cell polarity in the mouse prostate.
AB  - BACKGROUND: Dystroglycan is a cell-surface receptor for extracellular matrix
      proteins including laminins and perlecan. Prior studies have shown its
      involvement in assembly and/or maintenance of basement membrane structures, cell
      polarity and tissue morphogenesis; and its expression is often reduced in
      prostate and other cancers. However, the role of dystroglycan in normal
      epithelial tissues such as the prostate is unclear. METHODS: To investigate this,
      we disrupted dystroglycan expression in the prostate via a conditional gene
      targeting strategy utilizing Cre recombinase expressed in luminal prostate
      epithelial cells. RESULTS: Contrary to expectations, deletion of dystroglycan in
      luminal epithelial cells resulted in no discernable phenotype as judged by
      histology, basement membrane ultrastructure, localization of dystroglycan
      ligands, cell polarity or regenerative capacity of the prostate following
      castration. Dystroglycan expression remains in keratin-5-positive basal cells
      located in the proximal ducts where dystroglycan expression is elevated in
      regenerating prostates. CONCLUSIONS: Our results show that dystroglycan in
      luminal epithelial cells is not required for the maintenance of basement
      membranes, cell polarity or prostate regeneration. However, it is possible that
      persistent dystroglycan expression in the basal cell compartment may support
      these or other functions.

PMID- 20054821
TI  - Expression of toll-like receptor-9 is increased in poorly differentiated prostate
      tumors.
AB  - BACKGROUND: Toll-like receptor-9 (TLR9) is a cellular receptor for bacterial and
      vertebrate DNA. In addition to cells of the immune system, it is also expressed
      in various human cancer cell lines, including prostate cancer. We demonstrated
      previously that synthetic TLR9 ligands induce matrix metalloproteinase-13
      mediated invasion in TLR9-expressing prostate cancer cells in vitro. Other
      studies have suggested possible sex steroid regulation of the function of the
      various TLRs. The role of TLR9 in the pathophysiology of prostate or any cancer
      is, however, unknown. METHODS: Expression of TLR9, androgen receptor (AR), or the
      estrogen receptors alpha (ERalpha) and beta (ERbeta) were studied with
      immunohistochemistry in prostate cancer (n = 62) and benign prostatic hyperplasia
      (n = 45) specimens. TLR9 staining scores were compared with tumor stage, Gleason
      score, prostate-specific antigen (PSA) concentrations before tissue sampling and
      with the staining scores of AR, ERalpha, and ERbeta. RESULTS: TLR9 expression was
      statistically significantly increased in prostate cancer epithelium and stroma,
      as compared with the same cellular compartments in benign hyperplasia.
      Significantly increased (P = 0.04) TLR9 expression was detected in cancers with
      high Gleason score (>7, n = 23), as compared with lower Gleason scores (< or =7,
      n = 39). No statistically significant associations were detected between TLR9
      expression scores and PSA concentrations or tumor staging. Prostate
      adenocarcinoma cells were all positive for TLR9, AR, and ERbeta but negative for
      ERalpha expression. In cancer stroma cells, increased TLR9 expression was
      associated with increased ERalpha expression. CONCLUSIONS: Expression of TLR9 is
      increased in prostate cancer specimens, especially in the most poorly
      differentiated forms.

PMID- 20054820
TI  - Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of
      prostate cancer cells.
AB  - BACKGROUND: p21-activated kinase 6 (PAK6) is a serine/threonine kinase belonging
      to the p21-activated kinase (PAK) family. We investigated the role of PAK6 in
      radiation-induced cell death in human prostate cancer cells. METHODS: We used a
      short hairpin RNA (shRNA) strategy to stably knock down PAK6 in PC3 and DU145
      cells. Radiation sensitivities were compared in PAK6 stably knockdown cells
      versus the scrambled shRNA-expressing control cells. RESULTS: PAK6 mRNA and
      protein levels in PC3 and DU145 cells were upregulated upon exposure to 6 Gy of
      radiation. After irradiation, an increased percentage of apoptotic cells and
      cleaved caspase-3 levels were demonstrated in combination with a decrease in cell
      viability and a reduction in clonogenic survival in PAK6-knockdown cells. In
      addition, transfection with PAK6 shRNA blocked cells in a more radiosensitive G2
      M phase and increased levels of DNA double-strand breaks. We further explored the
      potential mechanisms by which PAK6 mediates resistance to radiation-induced
      apoptosis. Inhibition of PAK6 caused a decrease in Ser(112) phosphorylation of
      BAD, a proapoptotic member of the Bcl-2 family, which led to enhanced binding of
      BAD to Bcl-2 and Bcl-X(L) and release of cytochrome c culminating into caspase
      activation and cell apoptosis. CONCLUSIONS: The combination of PAK6 inhibition
      and irradiation resulted in significantly decreased survival of prostate cancer
      cells. The underlying mechanisms by which targeting PAK6 may improve radiation
      response seem to be multifaceted, and involve alterations in cell cycle
      distribution and impaired DNA double-strand break repair as well as relieved BAD
      phosphorylation.

PMID- 20054822
TI  - Characterization of NaV1.6-mediated Na+ currents in smooth muscle cells isolated
      from mouse vas deferens.
AB  - Patch-clamp experiments were performed to investigate the behavior of voltage
      activated inward currents in vas deferens myocytes from Na(V)1.6-null mice
      (Na(V)1.6(-/-)) lacking the expression of the Na(+) channel gene, Scn8a, and
      their wild-type littermates (Na(V)1.6(+/+)). Immunohistochemistry confirmed
      expression of Na(V)1.6 in the muscle of Na(V)1.6(+/+), but not Na(V)1.6(-/-), vas
      deferens. PCR analysis revealed that the only beta(1)-subunit gene expressed in
      Na(V)1.6(+/+) vas deferens was Scn1b. In Na(V)1.6(+/+) myocytes, the threshold
      for membrane currents evoked by 20 msec voltage ramps (-100 mV to 60 mV) was 
      38.5 +/- 4.6 mV and this was shifted to a more positive potential (-31.2 +/- 4.9
      mV) by tetrodotoxin (TTX). In Na(V)1.6(-/-) myocytes, the threshold was -30.4 +/-
      3.4 mV and there was no TTX-sensitive current. The Na(+) current (I(Na)) in
      Na(V)1.6(+/+) myocytes had a bell-shaped current-voltage relationship that peaked
      at approximately -10 mV. Increasing the duration of the voltage ramps beyond 20
      msec reduced the peak amplitude of I(Na). I(Na) displayed both fast (tau
      approximately 10 msec) and slow (tau approximately 1 sec) recovery from
      inactivation, the magnitude of the slow component increasing with the duration of
      the conditioning pulse (5-40 msec). During repetitive activation (5-40 msec
      pulses), I(Na) declined at stimulation frequencies > 0.5 Hz and at 10 Hz <or= 50%
      of the current remained. These findings indicate that I(Na) is due solely to
      Na(V)1.6 in Na(V)1.6(+/+) myocytes. The gating properties of these channels
      suggest they play a major role in regulating smooth muscle excitability,
      particularly in response to rapid depolarizing stimuli.

PMID- 20054823
TI  - The host defense peptide LL-37 activates the tumor-suppressing bone morphogenetic
      protein signaling via inhibition of proteasome in gastric cancer cells.
AB  - The human cathelicidin LL-37, a pleiotropic host defense peptide, is down
      regulated in gastric adenocarcinomas. We therefore investigated whether this
      peptide suppresses gastric cancer growth. LL-37 lowered gastric cancer cell
      proliferation and delayed G(1)-S transition in vitro and inhibits the growth of
      gastric cancer xenograft in vivo. In this connection, LL-37 increased the tumor
      suppressing bone morphogenetic protein (BMP) signaling, manifested as an increase
      in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction
      of p21(Waf1/Cip1). The anti-mitogenic effect, Smad1/5 phosphorylation, and
      p21(Waf1/Cip1) up-regulation induced by LL-37 were reversed by the knockdown of
      BMP receptor II. The activation of BMP signaling was paralleled by the inhibition
      of chymotrypsin-like and caspase-like activity of proteasome. In this regard,
      proteasome inhibitor MG-132 mimicked the effect of LL-37 by up-regulating BMP4
      expression and Smad1/5 phosphorylation. Further analysis of clinical samples
      revealed that LL-37 and p21(Waf1/Cip1) mRNA expressions were both down-regulated
      in gastric cancer tissues and their expressions were positively correlated.
      Collectively, we describe for the first time that LL-37 inhibits gastric cancer
      cell proliferation through activation of BMP signaling via a proteasome-dependent
      mechanism. This unique biological activity may open up novel therapeutic avenue
      for the treatment of gastric cancer.

PMID- 20054824
TI  - Extracellular beta-nicotinamide adenine dinucleotide (beta-NAD) promotes the
      endothelial cell barrier integrity via PKA- and EPAC1/Rac1-dependent actin
      cytoskeleton rearrangement.
AB  - Extracellular beta-NAD is known to elevate intracellular levels of calcium ions,
      inositol 1,4,5-trisphate and cAMP. Recently, beta-NAD was identified as an
      agonist for P2Y1 and P2Y11 purinergic receptors. Since beta-NAD can be released
      extracellularly from endothelial cells (EC), we have proposed its involvement in
      the regulation of EC permeability. Here we show, for the first time, that
      endothelial integrity can be enhanced in EC endogenously expressing beta-NAD
      activated purinergic receptors upon beta-NAD stimulation. Our data demonstrate
      that extracellular beta-NAD increases the transendothelial electrical resistance
      (TER) of human pulmonary artery EC (HPAEC) monolayers in a concentration
      dependent manner indicating endothelial barrier enhancement. Importantly, beta
      NAD significantly attenuated thrombin-induced EC permeability as well as the
      barrier-compromising effects of Gram-negative and Gram-positive bacterial toxins
      representing the barrier-protective function of beta-NAD. Immunofluorescence
      microscopy reveals more pronounced staining of cell-cell junctional protein VE
      cadherin at the cellular periphery signifying increased tightness of the cell
      cell contacts after beta-NAD stimulation. Interestingly, inhibitory analysis
      (pharmacological antagonists and receptor sequence specific siRNAs) indicates the
      participation of both P2Y1 and P2Y11 receptors in beta-NAD-induced TER increase.
      beta-NAD-treatment attenuates the lipopolysaccharide (LPS)-induced
      phosphorylation of myosin light chain (MLC) indicating its involvement in barrier
      protection. Our studies also show the involvement of cAMP-dependent protein
      kinase A and EPAC1 pathways as well as small GTPase Rac1 in beta-NAD-induced EC
      barrier enhancement. With these results, we conclude that beta-NAD regulates the
      pulmonary EC barrier integrity via small GTPase Rac1- and MLCP- dependent
      signaling pathways.

PMID- 20054825
TI  - Progranulin (granulin/epithelin precursor) and its constituent granulin repeats
      repress transcription from cellular promoters.
AB  - Progranulin (also known as granulin/epithelin precursor, GEP) is composed of
      seven granulin/epithelin repeats (granulins) and functions both as a full-length
      protein and as individual granulins. It is a secretory protein but a substantial
      amount of GEP is found inside cells, some in complexes with positive
      transcription elongation factor b (P-TEFb). GEP and certain granulins interact
      with the cyclin T1 subunit of P-TEFb, and with its HIV-1 Tat co-factor, leading
      to repression of transcription from the HIV promoter. We show that GEP lacking
      the signal peptide (GEPspm) remains inside cells and, like wild-type GEP,
      interacts with cyclin T1 and Tat. GEPspm represses transcription from the HIV-1
      promoter at the RNA level. Granulins that bind cyclin T1 are phosphorylated by P
      TEFb in vivo and in vitro on serine residues. GEPspm and those granulins that
      interact with cyclin T1 also inhibit transcription from cellular cad and c-myc
      promoters, which are highly dependent on P-TEFb, but not from the PCNA promoter.
      In addition, GEPspm and granulins repress transcriptional activation by VP16 or c
      Myc, proteins that bind and recruit P-TEFb to responsive promoters. These data
      suggest that intracellular GEP is a promoter-specific transcriptional repressor
      that modulates the function of cellular and viral transcription factors.

PMID- 20054826
TI  - Cdc20 proteolysis requires p38 MAPK signaling and Cdh1-independent APC/C
      ubiquitination during spindle assembly checkpoint activation by cadmium.
AB  - Cdc20, an activator of the anaphase promoting complex/cyclosome (APC/C) ubiquitin
      ligase, initiates the destruction of key mitotic regulators to facilitate
      mitosis, while it is negatively regulated by the spindle assembly checkpoint
      (SAC) to prevent premature anaphase entry. Activation of the p38 mitogen
      activated protein kinase could contribute to mitotic arrest, but the underlying
      mechanism is unknown. Here we report a novel pathway in which the p38 signaling
      triggers Cdc20 destruction under SAC elicited by cadmium, a human carcinogen. We
      found that the cadmium-induced prometaphase arrest was linked to decreased Cdc20
      and accumulated cyclin A protein levels in human cells, whereas the activity of
      cyclin B1-Cdk1 was unaffected. The Cdc20 half-life was markedly shortened along
      with its ubiquitination and degradation via 26S proteasome in cadmium-treated
      asynchronous or G(2)-enriched cells. Depletion of APC3 markedly suppressed the
      cadmium-induced Cdc20 ubiquitination and proteolysis, while depletion of Cdh1,
      another activator of APC/C, did not. Intriguingly, blockage of p38 activity
      restored the Cdc20 levels for continuing mitosis under cadmium, while inhibition
      of JNK activity had no effect. The cadmium-induced Cdc20 proteolysis was also
      suppressed during transient depletion of p38alpha or stable expression a dominant
      negative form of p38. Inhibition of p38 abolished the induction of Mad2-Cdc20
      APC3 complex by cadmium. Moreover, forced expression of MKK6-p38 signaling could
      promote Cdc20 degradation in a Cdh1-independent APC/C pathway. In summary,
      accelerated ubiquitination and proteolysis of Cdc20 is essential for prometaphase
      arrest that is mediated via the p38 signaling during SAC activation.

PMID- 20054827
TI  - Regulation of the membrane mucin Muc4 in corneal epithelial cells by proteosomal
      degradation and TGF-beta.
AB  - MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP-1
      (MUC4alpha) and a transmembrane subunit ASGP-2 (MUC4beta), which has been
      implicated in the protection of epithelial cell surfaces. In the rat stratified
      corneal epithelium Muc4 is found predominantly in the most superficial cell
      layers. Since previous studies in other tissues have shown that Muc4 is regulated
      by TGF-beta via a proteosomal degradation mechanism, we investigated the
      regulation of corneal Muc4 in stratified cultures of corneal epithelial cells.
      Application of proteosome or processing inhibitors led to increases in levels of
      Muc4, particularly in the basal and intermediate levels of the stratified
      cultures. These changes were accompanied by increases in Muc4 ubiquitination,
      chaperone association and incorporation into intracellular aggresomes. In
      contrast, treatment with TGF-beta resulted in reduced levels of Muc4, which were
      reversed by proteosome inhibition. The results support a model in which Muc4
      precursor is synthesized in all layers of the corneal epithelium, but Muc4 is
      degraded in basal and intermediate layers by a proteosomal mechanism at least
      partly dependent on TGF-beta inhibition of Muc4 processing.

PMID- 20054828
TI  - Chorioamnion plugging and the risk of preterm premature rupture of membranes
      after laser surgery in twin-twin transfusion syndrome.
AB  - OBJECTIVE: To examine the incidence of preterm premature rupture of membranes
      (PPROM) in pregnancies affected by twin-twin transfusion syndrome (TTTS) treated
      with laser photocoagulation where an absorbable gelatin sponge was used as a
      chorioamnion sealant of the fetoscopic access port. METHOD: A retrospective
      review was undertaken of consecutive cases undergoing fetoscopic directed laser
      surgery for TTTS between October 2006 and November 2008 at Texas Children's Fetal
      Center, in which an absorbable gelatin sponge, used as a chorioamnion 'plug', was
      placed at the conclusion of the intervention as a possible prophylactic measure
      to prevent PPROM. We excluded cases that had a failure of plug placement and
      those in which it was not attempted. PPROM was defined as rupture of membranes
      before 34 weeks' gestation. A comparison was performed between the PPROM group
      and a no-PPROM group to determine risk factors and outcomes. RESULTS: Successful
      plug placement occurred in 79 of 84 cases (94%) in which it was attempted after
      laser surgery, with a rate of PPROM of 34% in these patients. PPROM occurred at
      an average gestational age of 26.5 +/- 3.6 weeks, with an average procedure-to
      PPROM interval of 5.2 +/- 3.5 weeks. There were no statistically significant
      differences between the PPROM group and the no-PPROM group in maternal
      demographics or preoperative parameters including: amniotic fluid volumes in the
      recipient twin's gestational sac, volume of amnioreduction, and location of the
      placenta. The procedure-to-delivery interval for the total cohort (n = 79) was
      9.2 +/- 4.7 weeks, without a significant difference between the two groups (P =
      0.08). However, after exclusion of one PPROM outlier, the PPROM group had an
      average procedure-to-delivery time 2 weeks shorter than the group with no PPROM
      (P = 0.03). The live birth rates were similar in the PPROM and no-PPROM groups,
      at 77 and 73%, respectively. However, the average recipient's weight in the PPROM
      group was significantly lower than in the no-PPROM group (1321 +/- 493 vs. 1705
      +/- 576 g; P = 0.02). CONCLUSION: The rate of PPROM and the mean gestational age
      at delivery in pregnancies in which an absorbable gelatin sponge was used as a
      sealant of the fetoscopic port following laser photocoagulation for TTTS were
      comparable to those that have been reported by other laser centers where membrane
      sealants were not used. A randomized controlled trial should be considered to
      evaluate the effect of chorioamnion plugging.

PMID- 20054829
TI  - Isoniazid-resistance conferring mutations in Mycobacterium tuberculosis KatG:
      catalase, peroxidase, and INH-NADH adduct formation activities.
AB  - Mycobacterium tuberculosis catalase-peroxidase (KatG) is a bifunctional
      hemoprotein that has been shown to activate isoniazid (INH), a pro-drug that is
      integral to frontline antituberculosis treatments. The activated species,
      presumed to be an isonicotinoyl radical, couples to NAD(+)/NADH forming an
      isoniazid-NADH adduct that ultimately confers anti-tubercular activity. To better
      understand the mechanisms of isoniazid activation as well as the origins of KatG
      derived INH-resistance, we have compared the catalytic properties (including the
      ability to form the INH-NADH adduct) of the wild-type enzyme to 23 KatG mutants
      which have been associated with isoniazid resistance in clinical M. tuberculosis
      isolates. Neither catalase nor peroxidase activities, the two inherent enzymatic
      functions of KatG, were found to correlate with isoniazid resistance.
      Furthermore, catalase function was lost in mutants which lacked the Met-Tyr-Trp
      crosslink, the biogenic cofactor in KatG which has been previously shown to be
      integral to this activity. The presence or absence of the crosslink itself,
      however, was also found to not correlate with INH resistance. The KatG resistance
      conferring mutants were then assayed for their ability to generate the INH-NADH
      adduct in the presence of peroxide (t-BuOOH and H(2)O(2)), superoxide, and no
      exogenous oxidant (air-only background control). The results demonstrate that
      residue location plays a critical role in determining INH-resistance mechanisms
      associated with INH activation; however, different mutations at the same location
      can produce vastly different reactivities that are oxidant-specific. Furthermore,
      the data can be interpreted to suggest the presence of a second mechanism of INH
      resistance that is not correlated with the formation of the INH-NADH adduct.

PMID- 20054830
TI  - The solution structure of the Mg2+ form of soybean calmodulin isoform 4 reveals
      unique features of plant calmodulins in resting cells.
AB  - Soybean calmodulin isoform 4 (sCaM4) is a plant calcium-binding protein,
      regulating cellular responses to the second messenger Ca(2+). We have found that
      the metal ion free (apo-) form of sCaM4 possesses a half unfolded structure, with
      the N-terminal domain unfolded and the C-terminal domain folded. This result was
      unexpected as the apo-forms of both soybean calmodulin isoform 1 (sCaM1) and
      mammalian CaM (mCaM) are fully folded. Because of the fact that free Mg(2+) ions
      are always present at high concentrations in cells (0.5-2 mM), we suggest that
      Mg(2+) should be bound to sCaM4 in nonactivated cells. CD studies revealed that
      in the presence of Mg(2+) the initially unfolded N-terminal domain of sCaM4 folds
      into an alpha-helix-rich structure, similar to the Ca(2+) form. We have used the
      NMR backbone residual dipolar coupling restraints (1)D(NH), (1)D(C alpha H
      alpha), and (1)D(C'C alpha) to determine the solution structure of the N-terminal
      domain of Mg(2+)-sCaM4 (Mg(2+)-sCaM4-NT). Compared with the known structure of
      Ca(2+)-sCaM4, the structure of the Mg(2+)-sCaM4-NT does not fully open the
      hydrophobic pocket, which was further confirmed by the use of the fluorescent
      probe ANS. Tryptophan fluorescence experiments were used to study the
      interactions between Mg(2+)-sCaM4 and CaM-binding peptides derived from smooth
      muscle myosin light chain kinase and plant glutamate decarboxylase. These results
      suggest that Mg(2+)-sCaM4 does not bind to Ca(2+)-CaM target peptides and
      therefore is functionally similar to apo-mCaM. The Mg(2+)- and apo-structures of
      the sCaM4-NT provide unique insights into the structure and function of some
      plant calmodulins in resting cells.

PMID- 20054831
TI  - Enhanced solubilization of membrane proteins by alkylamines and polyamines.
AB  - Around 25% of proteins in living organisms are membrane proteins that perform
      many critical functions such as synthesis of biomolecules and signal
      transduction. Membrane proteins are extracted from the lipid bilayer and
      solubilized with a detergent for biochemical characterization; however, their
      solubilization is an empirical technique and sometimes insufficient quantities of
      proteins are solubilized in aqueous buffer to allow characterization. We found
      that addition of alkylamines and polyamines to solubilization buffer containing a
      detergent enhanced solubilization of membrane proteins from microsomes. The
      solubilization of polygalacturonic acid synthase localized at the plant Golgi
      membrane was enhanced by up to 9.9-fold upon addition of spermidine to the
      solubilization buffer. These additives also enhanced the solubilization of other
      plant membrane proteins localized in other organelles such as the endoplasmic
      reticulum and plasma membrane as well as that of an animal Golgi-localized
      membrane protein. Thus, addition of alkylamines and polyamines to solubilization
      buffer is a generally applicable method for effective solubilization of membrane
      proteins. The mechanism of the enhancement of solubilization is discussed.

PMID- 20054832
TI  - Prediction of structures of zinc-binding proteins through explicit modeling of
      metal coordination geometry.
AB  - Metal ions play an essential role in stabilizing protein structures and
      contributing to protein function. Ions such as zinc have well-defined
      coordination geometries, but it has not been easy to take advantage of this
      knowledge in protein structure prediction efforts. Here, we present a
      computational method to predict structures of zinc-binding proteins given
      knowledge of the positions of zinc-coordinating residues in the amino acid
      sequence. The method takes advantage of the "atom-tree" representation of
      molecular systems and modular architecture of the Rosetta3 software suite to
      incorporate explicit metal ion coordination geometry into previously developed de
      novo prediction and loop modeling protocols. Zinc cofactors are tethered to their
      interacting residues based on coordination geometries observed in natural zinc
      binding proteins. The incorporation of explicit zinc atoms and their coordination
      geometry in both de novo structure prediction and loop modeling significantly
      improves sampling near the native conformation. The method can be readily
      extended to predict protein structures bound to other metal and/or small chemical
      cofactors with well-defined coordination or ligation geometry.

PMID- 20054833
TI  - In memoriam: Walter Kauzmann (1916-2009).

PMID- 20054834
TI  - Effects of discontinuing benzodiazepine-derivative hypnotics on postural sway and
      cognitive functions in the elderly.
AB  - OBJECTIVE: Benzodiazepines (BZDs) have been reported to cause negative impacts on
      body stability and cognitive functions, which in turn could result in lethal
      incidents, including falls, especially in the elderly. This fact notwithstanding,
      no systematic trial has evaluated the feasibility and benefits of discontinuing
      BZD-derivative hypnotics in this population, which was addressed in this study.
      METHODS: In this 8-week open-label study, subjects aged >= 60 living in a nursing
      home who received BZD as a hypnotic were recruited. The BZD dose was tapered off
      over 3 weeks. The following assessments were performed 12 h post-dose at baseline
      and at endpoint: the Clinical Stabilometric Platform (CSP), the Critical Flicker
      Fusion Test (CFF), the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS), and the Leeds Sleep Evaluation Questionnaire
      (LSEQ). RESULTS: Thirty subjects were enrolled (mean +/- SD age = 79.1 +/- 8.9
      years, mean +/- SD flurazepam equivalent BZD dose = 19.5 +/- 10.9 mg/day).
      Psychiatric diagnoses (DSM-IV) of subjects were as follows: schizophrenia (n =
      12), primary insomnia (n = 9), dementia (n = 7), and bipolar disorder (n = 2). In
      26 completers, significant changes were found in a total length and a range of
      trunk motion with eyes closed. Significant improvements were also observed in the
      CFF and RBANS immediate memory, language, and attention index scores. Subjective
      worsening in sleep was not reported in those completers, assessed with the LSEQ.
      CONCLUSIONS: Our results suggest that discontinuation of BZD hypnotics is
      feasible in a majority of elderly persons and leads to an improvement in the
      stability of body and a recovery in cognitive functions during the daytime.

PMID- 20054835
TI  - Broad spectrum assessment of psychopathology and adaptive functioning with the
      Older Adult Behavior Checklist: a validation and diagnostic discrimination study.
AB  - OBJECTIVE: Self-administered by spouses and other collateral informants, the
      nationally normed Older Adult Behavior Checklist (OABCL) provides standardized
      data on diverse aspects of older adult psychopathology and adaptive functioning.
      We tested the validity of the Older Adult Behavior Checklist (OABCL) scale scores
      in terms of associations with diagnoses of dementia of the Alzheimer's type (DAT)
      and mood disorders (MD) and with nine measures of psychopathology, cognitive
      performance, and adaptive functioning. METHOD: Informants completed OABCLs for
      727 60-97-year-olds recruited from a memory disorders clinic, geriatric
      psychiatry clinic, and community-dwelling seniors. OABCL scale scores were tested
      for associations with DAT and MD diagnoses, as well as with scores on the
      Neuropsychiatric Inventory, Mini-Mental State Exam (MMSE), Clock Drawing Test,
      Alzheimer's Disease Assessment Scale, Geriatric Depression Scale, Clinical
      Dementia Rating, Dementia Severity Rating Scale, Trail Making Test Part A, and
      Instrumental Activities of Daily Living. RESULTS: OABCL scales had medium to
      large correlations with the nine other indices of functioning and significantly
      augmented MMSE discrimination between patients with DAT versus MD. OABCL scales
      also discriminated significantly between patients diagnosed with DAT versus MD
      and both these groups versus nonclinical subjects. CONCLUSIONS: Multiple OABCL
      scales had medium to large associations with diverse indices of functioning based
      on other kinds of data. The nationally normed OABCL provides new ways to
      integrate informant and self-report data to improve assessment of older adults.
      Specifically, the OABCL can provide discrimination between those who qualify for
      diagnoses of DAT versus MD versus neither diagnosis.

PMID- 20054836
TI  - The neuropsychological characteristics and regional cerebral blood flow of
      vascular cognitive impairment-no dementia.
AB  - OBJECTIVE: To investigate the neuropsychological characteristics of VCI-ND and to
      analyze the relationship between deficit pattern and regional cerebral blood flow
      (rCBF) in various VCI-ND subtypes defined by cognitive features. METHODS: 69
      subjects diagnosed with VCI-ND were recruited, then further classified into four
      subtypes: amnestic VCI-ND with single memory impairment (subtype I, n = 19),
      amnestic VCI-ND with multi-domain impairment (subtype II, n = 27), non-amnestic
      VCI-ND with single domain impairment (subtype III, n = 16), and non-amnestic VCI
      ND with multi-domain impairment (subtype IV, n = 7) according to their cognitive
      profile. Xenon-CT scan was administered to 31 VCI-ND patients (11 of subtype I,
      12 of subtype II and 8 of subtype III) and 10 normal controls (NC) to evaluate
      rCBF. RESULTS: The rate of different cognitive domains impairment in VCI-ND group
      ranged from 17 to 66%, lowest in clock drawing test and highest in time of
      modified version of trails making test A and maze tracing compared with NC,
      significant reduced rCBF was found in bilateral temporal lobe and thalamus, left
      periventricular white matter and caudate of subtype I, and in left temporal lobe
      and lenticular nucleus, bilateral periventricular white matter, white matter
      adjacent to left posterior horn of lateral ventricular and right caudate of
      subtype III, while significant reduced rCBF of subtype II was found in left
      subfrontal white matter, bilateral subtemporoparietal white matter, right
      lenticular nucleus, and in both regions of subtype I and III. CONCLUSIONS: The
      manifestation of rCBF in VCI-ND subtypes was consistent with performance of
      neuropsychological assessment.

PMID- 20054837
TI  - Evaluation of special and traditional dementia care in nursing homes: results
      from a cross-sectional study in Germany.
AB  - OBJECTIVE: Two-thirds of all residents in nursing homes in Germany suffer from
      some type of dementia. We investigated whether or not dementia patients receiving
      special (segregated or partially segregated) care exhibited a better quality of
      life than their counterparts residing in traditional nursing homes. METHODS: In a
      cross-sectional study in 28 special dementia care facilities in the city of
      Hamburg (admission criterion: mobile dementia patients with behaviour problems)
      594 residents were compared to a group of nursing home residents with dementia (n
      = 573) in 11 randomly selected nursing homes who were receiving traditional
      integrative care. Primary features such as cognitive and functional impairment,
      and behaviour problems were assessed by qualified nursing staff. RESULTS:
      Controlling for confounding variables, for dementia patients in special care
      units as compared to a reference group in traditional integrative care, the level
      of volunteer caregiver involvement was higher and there was more social contact
      to staff, fewer physical restraints, more involvement in home activities, and
      more frequent use of psychiatrists. There was no significant difference between
      the two care settings with regard to overall use of psychotropic drugs, however,
      residents in special dementia care used antipsychotics significantly less often
      and antidepressants more often. CONCLUSIONS: Significant differences for a number
      of indicators of the quality of life point in favour of special dementia care.
      Future evaluation studies ought to examine not only the general efficacy of types
      of care designed especially for dementia patients but also the efficacy of the
      respective individual components (i.e. caregiver ratio).

PMID- 20054838
TI  - Validation study of a French version of the modified telephone interview for
      cognitive status (F-TICS-m) in elderly women.
AB  - OBJECTIVE: To evaluate the performance of a French version of the modified
      Telephone Interview for Cognitive Status (F-TICS-m) in identifying cognitive
      decline among elderly women. METHODS: All women aged 72-86 participating in the
      'Etude Epidemiologique aupres de Femmes de l'Education Nationale' (E3N) cohort
      and living in or near Paris constituted the target population of the validation
      study. Volunteer women (n = 120) underwent both a 20-min telephone interview and
      a face-to-face neuropsychological examination at an interval of few days (median
      interval: 10 days). The telephone interview included F-TICS-m, as well as a
      recall of key elements of a short story, arithmetic/verbal problems and two
      verbal fluency tests. Neuropsychological examination consisted of a standardized
      battery of cognitive tests (including the Mini-Mental State Examination (MMSE),
      the Free and Cued Selective Reminding Test-FCSRT, Trailmaking tests A and B, the
      similarities subtest of the Wechsler Adult Intelligence Scale-III, etc.) the
      Instrumental Activities of Daily Living questionnaire, and the Geriatric
      Depression Scale. Neuropsychological examination led to classification of each
      subject as cognitively normal (n = 92) or impaired/demented (n = 28). RESULTS: F
      TICS-m showed satisfactory internal consistency (Cronbach's alpha = 0.69). It
      correlated linearly with MMSE (Pearson's r = 0.72). Concurrent validity against
      the gold-standard classification was satisfactory, with an area under the ROC
      curve (AUC) of 0.83. The combination of F-TICS-m and the other telephone tests
      had no additional effect on discrimination power in our sample (AUC = 0.81).
      CONCLUSION: F-TICS-m is a valid instrument for assessing the overall cognitive
      status of French elderly women. Its validity in men and its reproducibility
      warrant further studies.

PMID- 20054839
TI  - Prevalence of mental disorders and service utilization in seniors: results from
      the Canadian community health survey cycle 1.2.
AB  - OBJECTIVE: This paper examined the 12-month rate of mental disorders and
      subsequent service use among Canadian seniors aged 65-79 and 80 and over and
      adults aged 20-49 and 50-64. METHODS: This is a secondary analysis of data [n =
      33,695] of the population-based Canadian Community Health survey, Cycle 1.2 (CCHS
      1.2). Major Depressive Episodes (MDEs), specific Anxiety Disorders (AD) and
      Alcohol Abuse/Dependence rates were assessed. RESULTS: The 12-month rates for the
      two senior groups aged 65-79 and 80+ for MDEs, ADs, and Substance Dependence (SD)
      are 1.7% and 1.6%; 1.4% and 0.8%; and 0.1% and 0.0%, respectively. Seniors aged
      65-79 and 80+ had significantly lower rates than adults aged 20-49 and 50-64 for
      all mental disorders and SD. Among the total sample, seniors aged 65-79 and 80+
      had significantly lower utilization rates than adults aged 20-49 and 50-64 for
      all three provider categories (GP only, GP and Other Health Professional, Any
      Other Health Professional but GP). Females aged 65-79 and 80+ were less likely to
      have reported service use for mental health reasons as opposed to those females
      aged 20-49 and 50-64. Males aged 65-79 and 80+ were more likely to have reported
      having used mental health services in the past 12 months as opposed to males aged
      20-49 and 50-64. CONCLUSIONS: The presence of common mental disorders is lower in
      seniors as compared to younger adults. Age and gender influence mental health
      service utilization rates. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID- 20054840
TI  - Subtle deficits of attention after surgery: quantifying indicators of sub
      syndrome delirium.
AB  - OBJECTIVE: To determine whether attentional impairments are reliable
      neuropsychological markers of sub syndrome delirium. METHOD: A prospective cohort
      study with repeated assessment beginning pre-operatively and continuing through
      the first post-operative week. Computerized assessments of attention and the Mini
      Mental State Examination were administered with one hundred patients admitted for
      elective orthopedic surgery, 70 years and over and free of dementia. Acute change
      of cognitive status was used to identify cases of sub syndrome delirium. RESULTS:
      There were significant differences of post-surgical performance between the 'no
      delirium' and 'sub-syndrome delirium' groups of reaction time, global cognition,
      accuracy and greater variability of reaction time (p < 0.041). There were
      significant within subject main effects on reaction time (p = 0.001), variability
      of reaction time (p = 0.022) and MMSE (p = 0.000) across the cohort; but no
      significant interaction effect of 'diagnosis' * 'time' on the computerized
      measures of attention (p > 0.195). CONCLUSION: The distinction between people
      with sub syndrome delirium and no delirium is difficult to quantify but
      computerized measures of attention might provide a sensitive indicator. Sub
      syndrome delirium is an observable marker of a clinical abnormality that should
      be exploited to improve care management for vulnerable patients.

PMID- 20054841
TI  - Using spaced retrieval and Montessori-based activities in improving eating
      ability for residents with dementia.
AB  - OBJECTIVES: To construct a training protocol for spaced retrieval (SR) and to
      investigate the effectiveness of SR and Montessori-based activities in decreasing
      eating difficulty in older residents with dementia. METHODS: A single evaluator,
      blind, and randomized control trial was used. Eighty-five residents with dementia
      were chosen from three special care units for residents with dementia in long
      term care facilities in Taiwan. To avoid any confounding of subjects, the three
      institutions were randomized into three groups: spaced retrieval, Montessori
      based activities, and a control group. The invention consisted of three 30-40 min
      sessions per week, for 8 weeks. RESULTS: After receiving the intervention, the
      Edinburgh Feeding Evaluation in Dementia (EdFED) scores and assisted feeding
      scores for the SR and Montessori-based activity groups were significantly lower
      than that of the control group. However, the frequencies of physical assistance
      and verbal assistance for the Montessori-based activity group after intervention
      were significantly higher than that of the control group, which suggests that
      residents who received Montessori-based activity need more physical and verbal
      assistance during mealtimes. In terms of the effects of nutritional status after
      intervention, Mini-Nutritional Assessment (MNA) in the SR group was significantly
      higher than that of the control group. CONCLUSION: This study confirms the
      efficacy of SR and Montessori-based activities for eating difficulty and eating
      ability. A longitudinal study to follow the long-term effects of SR and
      Montessori-based activities on eating ability and nutritional status is
      recommended.

PMID- 20054842
TI  - Epidemiologic mapping of Florida childhood cancer clusters.
AB  - BACKGROUND: Childhood cancer remains the leading cause of disease-related
      mortality for children. Whereas, improvement in care has dramatically increased
      survival, the risk factors remain to be fully understood. The increasing
      incidence of childhood cancer in Florida may be associated with possible cancer
      clusters. We aimed, in this study, to identify and confirm possible childhood
      cancer clusters and their subtypes in the state of Florida. METHODS: We conducted
      purely spatial and space-time analyzes to assess any evidence of childhood
      malignancy clusters in the state of Florida using SaTScan. Data from the Florida
      Association of Pediatric Tumor Programs (FAPTP) for the period 2000-2007 were
      used in this analysis. RESULTS: In the purely spatial analysis, the relative
      risks (RR) of overall childhood cancer persisted after controlling for
      confounding factors in south Florida (SF) (RR = 1.36, P = 0.001) and northeastern
      Florida (NEF) (RR = 1.30, P = 0.01). Likewise, in the space-time analysis, there
      was a statistically significant increase in cancer rates in SF (RR = 1.52, P =
      0.001) between 2006 and 2007. The purely spatial analysis of the cancer subtypes
      indicated a statistically significant increase in the rate of leukemia and
      brain/CNS cancers in both SF and NEF, P < 0.05. The space-time analysis indicated
      a statistically significant sizable increase in brain/CNS tumors (RR = 2.25, P =
      0.02) for 2006-2007. CONCLUSIONS: There is evidence of spatial and space-time
      childhood cancer clustering in SF and NEF. This evidence is suggestive of the
      presence of possible predisposing factors in these cluster regions. Therefore,
      further study is needed to investigate these potential risk factors.

PMID- 20054843
TI  - Childhood cancer clustering in Florida: weighing the evidence.

PMID- 20054844
TI  - Radiofrequency exposure on fast patrol boats in the Royal Norwegian Navy--an
      approach to a dose assessment.
AB  - Epidemiological studies related to radiofrequency (RF) electromagnetic fields
      (EMF) have mainly used crude proxies for exposure, such as job titles, distance
      to, or use of different equipment emitting RF EMF. The Royal Norwegian Navy
      (RNoN) has measured RF field emitted from high-frequency antennas and radars on
      several spots where the crew would most likely be located aboard fast patrol
      boats (FPB). These boats are small, with short distance between the crew and the
      equipment emitting RF field. We have described the measured RF exposure aboard
      FPB and suggested different methods for calculations of total exposure and annual
      dose. Linear and spatial average in addition to percentage of ICNIRP and squared
      deviation of ICNIRP has been used. The methods will form the basis of a job
      exposure matrix where relative differences in exposure between groups of crew
      members can be used in further epidemiological studies of reproductive health.

PMID- 20054845
TI  - Identification of the major metabolites of quinocetone in swine urine using ultra
      performance liquid chromatography/electrospray ionization quadrupole time-of
      flight tandem mass spectrometry.
AB  - Quinocetone (QCT), 3-methyl-2-cinnamoylquinoxaline-1,4-dioxide, is a quinoxaline
      N,N-dioxide used in veterinary medicine as a feed additive. QCT is broadly used
      in China to promote animal growth, but few studies have been performed to reveal
      the metabolism of QCT in animals until now. In the present study, the metabolites
      of QCT in swine urine were investigated using ultra-performance liquid
      chromatography/electrospray ionization quadrupole time-of-flight mass
      spectrometry (UPLC/ESI-QTOF-MS). Multiple scans of metabolites in MS and MS/MS
      modes and accurate mass measurements were performed simultaneously through data
      dependent acquisition. Most measured mass errors were less than +/-5 mDa for both
      protonated molecules and product ions using external mass calibration. The
      structures of metabolites and their product ions were easily and reliably
      characterized based on the accurate MS(2) spectra and known structure of QCT. As
      expected, extensive metabolism was observed in swine urine. Thirty-one
      metabolites were identified in swine urine, most of which were reported for the
      first time. The results reveal that the N-O group reduction at position 1 and the
      hydroxylation reaction occurring at the methyl group, the side chain or on the
      benzene ring are the main metabolic pathways of quinocetone in swine urine. There
      was abundant production of 1-desoxyquinocetone and hydroxylation metabolites of 1
      desoxyquinocetone. The proposed metabolic pathway of quinocetone in vivo can be
      expected to play a key role in food safety evaluations.

PMID- 20054847
TI  - Genetic variants in the noncoding region of RPS19 gene in Diamond-Blackfan
      anemia: potential implications for phenotypic heterogeneity.
AB  - Mutations in the RPS19 gene have been identified in 25% of individuals affected
      by Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia characterized
      by an aregenerative anemia and a variety of malformations. More than 60 mutations
      in the five coding exons of RPS19 have been described to date. We previously
      reported a mutation (c.-1 + 26G>T) and an insertion at -631 upstream of ATG (c.
      147_-146insGCCA) in the noncoding region. Because DBA phenotype is extremely
      heterogeneous from silent to severe and because haploinsufficiency seems to play
      a role in this process, it is likely that genetic variations in the noncoding
      regions affecting translation of RPS19 can modulate the phenotypic expression of
      DBA. However, to date, very few studies have addressed this question
      comprehensively. In this study, we performed detailed sequence analysis of the
      RPS19 gene in 239 patients with DBA and 110 of their relatives. We found that
      6.2% of the patients with DBA carried allelic variations upstream of ATG: 3.3%
      with c.-1 + 26G>T; 2.5% with c.-147_-146insGCCA; and 0.4% with c.-174G>A.
      Interestingly, the c.-147_-146insGCCA, which has been found in a black American
      and French Caribbean control population, was not found in 500 Caucasian control
      chromosomes we studied. However, it was found in association with the same
      haplotype distribution of four intronic polymorphisms in our patients with DBA.
      Although a polymorphism, the frequency of this variant in the patients with DBA
      and its association with the same haplotype raises the possibility that this
      polymorphism and the other genetic variations in the noncoding region could play
      a role in DBA pathogenesis.

PMID- 20054848
TI  - Identification and molecular characterization of the --CAMPANIA deletion, a novel
      alpha (0) -thalassemic defect, in two unrelated Italian families [corrected].

PMID- 20054849
TI  - Role of pretreatment 18FDG-PET/CT in surgical decision-making for head and neck
      cancers.
AB  - BACKGROUND: Despite widespread use, the utility of pretreatment positron emission
      tomography/computed tomography (PET/CT) remains undefined. In this study, we aim
      to determine its accuracy in nodal disease. METHODS: In all, 111 patients managed
      between 2003 and 2007 were analyzed. RESULTS: For squamous cell cancers (SCCs)
      with any increased nodal uptake (mild to high), sensitivity, specificity,
      positive predictive values (PPVs), and negative predictive values (NPVs) were
      75%, 95%, 85%, and 90%. However, if PET was deemed positive for only moderate to
      high uptake, sensitivity, specificity, PPV, and NPV were 71%, 95%, 85%, and 89%.
      In patients undergoing elective neck dissection, the accuracy was lower: for any
      increased uptake, sensitivity, specificity, PPV, and NPV were 66%, 96%, 83%, and
      92%, whereas for moderate to high uptake, these were 52%, 97%, 79%, and 89%.
      CONCLUSIONS: Despite advances in PET/CT technology, these statistics suggest that
      PET/CT is not sufficiently accurate to direct superselective neck dissections, or
      to guide therapeutic decisions in the N0 neck.

PMID- 20054850
TI  - Predictors of functional decline in locally advanced head and neck cancer
      patients from south Brazil.
AB  - BACKGROUND: Functional decline in Brazilian patients with head and neck squamous
      cell carcinoma (HNSCC) is associated with impaired recovery, quality of life, and
      health care costs. METHODS: Sixty patients enrolled at the regional oncology
      center in Curitiba, Brazil, were assessed over 6 months for toxicities,
      nutritional status, anthropometry, fatigue, stress, and functionality. RESULTS:
      Severe mid-arm and mid-calf circumference depletion accompanied weight loss.
      Total fatigue score increased 64% (p < .001), as did perceived stress and serum
      cortisol (p = .01). Instrumental activities of daily living (IADL) dependence
      doubled, and activities of daily living (ADL) dependence quadrupled (p < .001).
      Difficulty chewing or swallowing, weight loss, fatigue, perceived stress, and
      IADL dependence accounted for 48.2% of ADL dependence. CONCLUSIONS: The physical
      and psychological impact of HNSCC and its treatment are universally experienced;
      yet, screening and intervention for symptoms such as fatigue and stress are not
      typical clinical practice. Moreover, assessment of functional status is usually
      limited to chewing and swallowing. This study identified symptoms that require
      systematic intervention and randomized trials with functional independence as the
      outcome.

PMID- 20054852
TI  - Immunotherapy using allogeneic squamous cell tumor-dendritic cell fusion hybrids.
AB  - BACKGROUND: Tumor-associated antigens (TAAs) are known to be immunotherapy
      targets; thus tumor-sharing TAA may be used as a fusion hybrid partner to confer
      protection against subsequent tumor challenge. METHODS: The squamous cell
      carcinomas (SCCs), SCCVII and B4B8, were used in C3H/HEN mice: SCCVII (H-2(k)) is
      syngeneic, B4B8 (H-2(d)) is allogeneic. Experiments using tumor alone included
      hyperimmunization schedule, subdermal and intranodal routes. Mice were challenged
      2 weeks later. Fusion hybrids were created from both SCC tumor cell lines and
      syngeneic dendritic cells (DCs). These were delivered intranodally for
      immunization, and mice were challenged with tumor 2 weeks later. RESULTS: Only
      syngeneic tumor given subdermally was able to protect after tumor challenge 2
      weeks later. Hyperimmunization schedule did not alter these findings. However,
      fusion hybrid immunization from both allogeneic and syngeneic SCCs conferred
      protection after tumor challenge. CONCLUSIONS: Allogeneic tumor-DC fusion hybrids
      targeting TAA can protect against subsequent tumor challenge.

PMID- 20054853
TI  - Modern management and pathophysiology of ranula: literature review.
AB  - BACKGROUND: There is a lack of consensus about the appropriate treatment of
      ranula. The objective of the present investigation was to produce a scientific
      basis for treatment. METHODS: A review of the relevant literature is interpreted
      in the light of improved knowledge about the local anatomy and the
      pathophysiology of the salivary glands. RESULTS: The oral and plunging ranulas
      are cystic extravasation mucoceles that arise from the sublingual gland and
      usually from a torn duct of Rivinus. The sublingual gland is a spontaneous
      secretor and the salivary flow is resistant to obstruction, which is caused by
      fibrosis induced by the extravasation. The submandibular gland is not a
      spontaneous secretor, is less resistant, and does not give rise to ranulas.
      CONCLUSIONS: Effective treatment is removal of the involved unit of the
      sublingual gland or inducing sufficient fibrosis to seal the leak through which
      the mucus extravasates.

PMID- 20054854
TI  - Postmarketing in vitro/in vivo assessment of fixed dose combination products of
      first line antiretrovirals.
AB  - The purpose of this study was to evaluate the postmarket pharmaceutical
      equivalence, stability and bioequivalence of generic and innovator fixed dose
      combination products of lamivudine (3TC) and zidovudine (AZT) 150/300 mg tablets
      available in Nigeria. An isocratic HPLC-UV method was developed and validated for
      the quantitative determination of 3TC and AZT in human plasma and pharmaceutical
      samples. The model independent f(2) similarity factor was used to compare the
      dissolution profiles of the two products stored at accelerated and long-term
      stability conditions for 6 months. The f(2) values for 3TC and AZT in both
      products were found to be greater than 51. Also, the tablets were stable
      according to the USP potency and drug dissolution criteria with more than 80% of
      drug dissolution in 30 min indicating the pharmaceutical equivalence of the two
      products. The 90% confidence interval for the ratios of generic/innovator
      pharmacokinetic parameters for 3TC/AZT were 73.5-112.6/63.4-95.8 (C(max)); 68.5
      105.6/68.0-114.8 (AUC(0-t)); and 64.2-106.2/80.1-120.3 (AUC(0-infinity))
      respectively. The pharmacokinetic parameters failed to fully demonstrate
      bioequivalence between the products. The results underscored the importance of
      assessing the quality of the combination drug products that would ensure the
      safety and efficacy of the generic drug products available in the market.

PMID- 20054857
TI  - ULBP2 and RAET1E NKG2D ligands are independent predictors of poor prognosis in
      ovarian cancer patients.
AB  - The human activating immune receptor, NKG2D, binds to a diverse array of cellular
      ligands of the MIC and unique long 16 (UL16)-binding protein (ULBP)/retinoic acid
      early transcript (RAET) family. NKG2D is thought to participate in anticancer
      immune responses. By using tissue microarrays representing over 300 patients with
      defined clinicopathological factors, we present the first comprehensive screen of
      the expression of all NKG2D ligands in primary ovarian cancers. NKG2D ligands
      were expressed by the majority of tumors; however, the level of expression varied
      considerably. By categorizing each tumor as having negative, low or high
      expression, it was shown that high expression of several NKG2D ligands is
      inversely correlated with disease survival. Patients whose tumors had high
      expression of RAET1E (p = 0.037), ULBP1 (p = 0.036) and ULBP3 (p = 0.004)
      surviving a median of 11, 14 and 11 months, respectively, compared with disease
      specific survival of 29, 30 and 25 months in patients whose tumors showed no
      expression of these ligands. These results contrast with previous findings
      showing that high level NKG2D ligand expression is associated with good prognosis
      in colorectal cancer and suggest a fundamental difference in the involvement of
      NKG2D-mediated immunity in these two types of cancer. By using multivariate
      analysis, the factors retaining independent prognostic significance were
      International Federation of Gynecologists and Obstetricians stage (p < 0.001),
      presence of residual disease (p = 0.003), ULBP2 (p = 0.042) and RAET1E (p =
      0.030).

PMID- 20054856
TI  - Preterm delivery among female survivors of childhood, adolescent and young
      adulthood cancer.
AB  - We studied the deliveries of female cancer survivors and female siblings in a
      population-based setting in Finland. Nationwide cancer and birth registries were
      merged to identify 1,309 first postdiagnosis deliveries of early-onset (diagnosed
      under age 35) female patients with cancer and 5,916 first deliveries of female
      siblings occurring in 1987-2006. Multiple logistic regression models were used to
      estimate risk of preterm (<37 weeks), low birth weight (<2500 g) and small-for
      gestational-age deliveries. The risk of preterm delivery among cancer survivors
      compared with siblings was overall increased [odds ratio (OR) 1.46, 95%
      confidence interval (CI) 1.14-1.85], the increase in risk being visible in all
      diagnostic age groups. Risk of low birth weight (LBW) was also significantly
      increased (OR 1.68; 95% CI 1.29-2.18) but not after adjustment for duration of
      pregnancy (OR 1.11; 95% CI 0.76-1.64). Neither was the risk of small-for
      gestational-age (SGA) increased. The risk of preterm delivery was most pronounced
      in survivors delivering 10 years or more after diagnosis. Site-specific analyses
      indicated that survivors of germ cell tumors and central nervous system (CNS)
      tumors were at increased risk of preterm delivery, although numbers were small.
      In childhood survivors, kidney tumors formed the main cause of preterm delivery.
      Pediatric, adolescent and young adult cancer survivors are at risk for preterm
      delivery. Heightened surveillance is recommended especially for Wilms', germ cell
      and CNS tumor survivors. Such adverse pregnancy outcomes can occur a decade or
      more after cancer diagnosis, indicating a continued need for obstetric awareness,
      surveillance and counseling in former patients with cancer.

PMID- 20054858
TI  - Pulmonary squamous cell carcinoma associated with repaired congenital
      tracheoesophageal fistula and esophageal atresia.
AB  - We report a 19-year-old man with pulmonary squamous cell carcinoma (SCC) who had
      a history of vertebral, anal, cardiac, tracheal, esophageal, renal, and radial
      limb defects (VACTERL) association and tracheoesophageal fistula (TEF) +
      esophageal atresia (EA) repair as an infant. Children that undergo TEF + EA
      repair may have an increased risk for developing cancer as they reach adulthood.

PMID- 20054859
TI  - Return of FEV1 after pulmonary exacerbation in children with cystic fibrosis.
AB  - RATIONALE: Lung function (FEV(1)) generally improves during treatment of
      pulmonary exacerbations in patients with cystic fibrosis (CF). However, it is
      unclear how often return to previous baseline FEV(1) is achieved. OBJECTIVES: (1)
      To determine the proportion of pediatric patients with CF treated for a pulmonary
      exacerbation who fail to recover to baseline FEV(1) and (2) to identify factors
      associated with this failure. METHODS: We performed a case-control analysis of
      patients from a single pediatric CF center admitted for their first pulmonary
      exacerbation in 2001-2006. Patients were considered to have recovered to baseline
      FEV(1) if their best FEV(1) within the 3 months following treatment was >or=95%
      of the best FEV(1) during the 6 months prior to treatment. Logistic regression
      was used to estimate associations between clinical characteristics and failure to
      regain baseline FEV(1). RESULTS: Of 104 patients, 24 (23.1%) did not recover to
      baseline FEV(1). The adjusted odds ratio of failure to recover to baseline FEV(1)
      was 1.49 (95% confidence interval [CI] 1.20, 1.86) for every 5% greater decline
      in FEV(1) from baseline to admission. In exploratory analyses, the adjusted odds
      ratios for the failure to recover to baseline were also significantly higher for
      patients who were evaluated in our CF clinic more frequently between the baseline
      measurement and admission, were younger, or were insured by Medicaid.
      CONCLUSIONS: Approximately one in four patients with CF failed to recover to
      baseline lung function after a pulmonary exacerbation despite treatment with
      intravenous antibiotics. Failure to recover to baseline was associated with the
      degree of decline in FEV(1) that had occurred prior to hospital admission,
      suggesting opportunities for earlier intervention to improve lung function
      outcomes. Additional studies are needed to determine how the failure to recover
      to baseline affects subsequent FEV(1) decline.

PMID- 20054860
TI  - Cell phone intervention to improve adherence: cystic fibrosis care team, patient,
      and parent perspectives.
AB  - BACKGROUND: Treatment regimens for patients with cystic fibrosis (CF) are time
      consuming and complex, resulting in consistently low adherence rates. To date,
      few studies have evaluated innovative technologies to improve adherence in this
      population. Current infection control guidelines for patients with CF seek to
      minimize patient-to-patient transmission of potential pathogens. Thus,
      interventions must avoid face-to-face contact and be delivered individually,
      limiting opportunities for peer support. This study aimed to develop and assess a
      web-enabled cell phone, CFFONE, designed to provide CF information and social
      support to improve adherence in adolescents with CF. METHODS: The acceptability,
      feasibility, and utility of CFFONE were evaluated with health care professionals
      (n = 17) adolescents with CF aged 11-18 years old (n = 12), adults with CF aged
      21-36 years old (n = 6), parents of adolescents with CF (n = 12), and technology
      experts (n = 8). Adolescents also tested a prototype of CFFONE (n = 9).
      Qualitative and quantitative data were collected. RESULTS: Focus group data with
      health care professionals indicated a need for this intervention, and indicated
      that CFFONE would be likely to improve knowledge and social support, and somewhat
      likely to improve adherence. Adolescent, adults, and parents all rated CFFONE as
      likely to improve adherence. Technology experts rated the prototype design and
      format as appropriate. CONCLUSIONS: The current study provided some support from
      key stakeholders for this intervention to improve adherence in adolescents with
      CF. Next steps include a multi-center trial of the efficacy and safety of CFFONE.

PMID- 20054861
TI  - Severity of bronchopulmonary dysplasia and increased risk of feeding desaturation
      and growth delay in very low birth weight preterm infants.
AB  - Oral feeding has been reported to compromise breathing among preterm infants with
      bronchopulmonary dysplasia (BPD) during hospitalization or shortly after
      discharge. However, limited information was available concerning whether preterm
      infants with BPD remain vulnerable to feeding and growth insufficiency after a
      longer term of follow-up. The purpose of this study was therefore to examine the
      effect of severity of BPD on pulse oxygen saturation (SpO(2)) during feeding and
      growth in very low birth weight (VLBW) preterm infants during infancy. Seventy
      two preterm infants with VLBW and 15 term infants were prospectively examined
      their growth and SpO(2) during feeding at 2, 4, and 6 months of corrected age.
      The severity of BPD was graded in VLBW infants according to the American National
      Institutes of Health consensus definition. In comparison to VLBW infants with
      mild BPD and term infants, VLBW infants with severe BPD showed significantly
      lower mean levels of SpO(2) during feeding at 2-6 months corrected age (P <
      0.05). Those with severe BPD further exhibited higher rates of growth delay
      (weight < 10th percentile) throughout the study period. Among VLBW infants,
      severe BPD had an adverse relation with subsequent weight measures after
      adjustment for medical and demographic confounding variables (beta = -904 g, P =
      0.03). The consensus BPD definition is useful to identify those preterm infants
      who are at greater risk of feeding desaturation and growth delay during infancy
      and close monitoring of SpO(2) during feeding should be advised.

PMID- 20054862
TI  - Late presentation of congenital diaphragmatic hernia in patients with cystic
      fibrosis.
AB  - Late presentation of congenital diaphragmatic hernia (CDH) is unusual, especially
      in patients with cystic fibrosis (CF). To our knowledge, cases of CDH in CF
      patients and the combined effects on lung function have not been previously
      described. Here we report two cases of late presenting CDH in CF patients and
      describe effects on lung function. Late presentation of CDH in CF patients can
      cause gastrointestinal or respiratory symptoms and requires a high index of
      suspicion as well as proper interpretation of imaging. In patients with CF and
      CDH, lung function abnormalities could include obstructive, restrictive defects,
      or combined defects.

PMID- 20054863
TI  - Distinguishing between mouse and human pluripotent stem cell regulation: the best
      laid plans of mice and men.
AB  - Pluripotent stem cells (PSCs) have been derived from the embryos of mice and
      humans, representing the two major sources of PSCs. These cells are universally
      defined by their developmental properties, specifically their self-renewal
      capacity and differentiation potential which are regulated in mice and humans by
      complex transcriptional networks orchestrated by conserved transcription factors.
      However, significant differences exist in the transcriptional networks and
      signaling pathways that control mouse and human PSC self-renewal and lineage
      development. To distinguish between universally applicable and species-specific
      features, we collated and compared the molecular and cellular descriptions of
      mouse and human PSCs. Here we compare and contrast the response to signals
      dictated by the transcriptome and epigenome of mouse and human PSCs that will
      hopefully act as a critical resource to the field. These analyses underscore the
      importance of accounting for species differences when designing strategies to
      capitalize on the clinical potential of human PSCs.

PMID- 20054864
TI  - Inhibition of aldehyde dehydrogenase expands hematopoietic stem cells with
      radioprotective capacity.
AB  - Hematopoietic stem cells (HSCs) are enriched for aldehyde dehydrogenase (ALDH)
      activity and ALDH is a selectable marker for human HSCs. However, the function of
      ALDH in HSC biology is not well understood. We sought to determine the function
      of ALDH in regulating HSC fate. Pharmacologic inhibition of ALDH with
      diethylaminobenzaldehyde (DEAB) impeded the differentiation of murine CD34(-)c
      kit(+)Sca-1(+)lineage(-) (34(-)KSL) HSCs in culture and facilitated a ninefold
      expansion of cells capable of radioprotecting lethally irradiated mice compared
      to input 34(-)KSL cells. Treatment of bone marrow (BM) 34(-)KSL cells with DEAB
      caused a fourfold increase in 4-week competitive repopulating units, verifying
      the amplification of short-term HSCs (ST-HSCs) in response to ALDH inhibition.
      Targeted siRNA of ALDH1a1 in BM HSCs caused a comparable expansion of
      radioprotective progenitor cells in culture compared to DEAB treatment,
      confirming that ALDH1a1 was the target of DEAB inhibition. The addition of all
      trans retinoic acid blocked DEAB-mediated expansion of ST-HSCs in culture,
      suggesting that ALDH1a1 regulates HSC differentiation via augmentation of
      retinoid signaling. Pharmacologic inhibition of ALDH has therapeutic potential as
      a means to amplify ST-HSCs for transplantation purposes.

PMID- 20054865
TI  - CCAAT/enhancer binding protein beta regulates stem cell activity and specifies
      luminal cell fate in the mammary gland.
AB  - The bZIP transcription factor C/EBP beta is important for mammary gland
      development and its expression is deregulated in human breast cancer. To
      determine whether C/EBP beta regulates mammary stem cells (MaSCs), we employed
      two different knockout strategies. Using both a germline and a conditional
      knockout strategy, we demonstrate that mammosphere formation was significantly
      decreased in C/EBP beta-deficient mammary epithelial cells (MECs). Functional
      limiting dilution transplantation assays indicated that the repopulating ability
      of C/EBP beta-deleted MECs was severely impaired. Serial transplantation
      experiments demonstrated that C/EBP beta deletion resulted in decreased outgrowth
      potential and premature MaSC senescence. In accord, fluorescence-activated cell
      sorting analysis demonstrated that C/EBP beta-null MECs contained fewer MaSCs,
      the loss of luminal progenitors and an increase in differentiated luminal cells
      as compared with wild-type. Gene profiling of C/EBP beta-null stem cells revealed
      an alteration in cell fate specification, exemplified by the expression of basal
      markers in the luminal compartment. Thus, C/EBP beta is a critical regulator of
      both MaSC repopulation activity and luminal cell lineage commitment. These
      findings have critical implications for understanding both stem cell biology and
      the etiology of different breast cancer subtypes.

PMID- 20054866
TI  - MicroRNA-30d promotes tumor invasion and metastasis by targeting Galphai2 in
      hepatocellular carcinoma.
AB  - The pathological relevance and significance of microRNAs (miRNAs) in
      hepatocarcinogenesis have attracted much attention in recent years; however,
      little is known about the underlying molecular mechanisms through which miRNAs
      are involved in the development and progression of hepatocellular carcinoma
      (HCC). In this study, we demonstrate that miR-30d is frequently up-regulated in
      HCC and that its expression is highly associated with the intrahepatic metastasis
      of HCC. Furthermore, the enhanced expression of miR-30d could promote HCC cell
      migration and invasion in vitro and intrahepatic and distal pulmonary metastasis
      in vivo, while silencing its expression resulted in a reduced migration and
      invasion. Galphai2 (GNAI2) was identified as the direct and functional target of
      miR-30d with integrated bioinformatics analysis and messenger RNA array assay.
      This regulation was further confirmed by luciferase reporter assays. In addition,
      our results, for the first time, showed that GNAI2 was frequently suppressed in
      HCC by way of quantitative reverse-transcription polymerase chain reaction and
      immunohistochemical staining assays. The increase of the GNAI2 expression
      significantly inhibits, whereas knockdown of the GNAI2 expression remarkably
      enhances HCC cell migration and invasion, indicating that GNAI2 functions as a
      metastasis suppressor in HCC. The restoration of GNAI2 can inhibit miR-30d
      induced HCC cell invasion and metastasis. CONCLUSION: The newly identified miR
      30d/GNAI2 axis elucidates the molecular mechanism of HCC cell invasion and
      metastasis and represents a new potential therapeutic target for HCC treatment.

PMID- 20054867
TI  - Thiazolidinediones as potent inducers of hepatocyte growth factor.

PMID- 20054868
TI  - Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent
      suppression of peroxisome proliferator-activated receptor alpha activity.
AB  - Kupffer cells have been implicated in the pathogenesis of various liver diseases.
      However, their involvement in metabolic disorders of the liver, including fatty
      liver disease, remains unclear. The present study sought to determine the impact
      of Kupffer cells on hepatic triglyceride storage and to explore the possible
      mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by
      chronic high-fat feeding were treated for 1 week with clodronate liposomes, which
      cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80,
      and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of
      Kupffer cells from the liver. Also, expression of complement components C1, the
      chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and
      IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly
      decreased liver triglyceride and glucosylceramide levels concurrent with
      increased expression of genes involved in fatty acid oxidation including
      peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine
      palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2).
      Treatment of mice with IL-1beta decreased expression of PPARalpha and its target
      genes, which was confirmed in primary hepatocytes. Consistent with these data, IL
      1beta suppressed human and mouse PPARalpha promoter activity. Suppression of
      PPARalpha promoter activity was recapitulated by overexpression of nuclear factor
      kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of
      putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with
      the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data
      point toward important cross-talk between Kupffer cells and hepatocytes in the
      regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver
      triglycerides are at least partially mediated by IL-1beta, which suppresses
      PPARalpha expression and activity.

PMID- 20054869
TI  - Integrated approach for the identification of human hepatocyte nuclear factor
      4alpha target genes using protein binding microarrays.
AB  - Hepatocyte nuclear factor 4 alpha (HNF4alpha), a member of the nuclear receptor
      superfamily, is essential for liver function and is linked to several diseases
      including diabetes, hemophilia, atherosclerosis, and hepatitis. Although many DNA
      response elements and target genes have been identified for HNF4alpha, the
      complete repertoire of binding sites and target genes in the human genome is
      unknown. Here, we adapt protein binding microarrays (PBMs) to examine the DNA
      binding characteristics of two HNF4alpha species (rat and human) and isoforms
      (HNF4alpha2 and HNF4alpha8) in a high-throughput fashion. We identified
      approximately 1400 new binding sequences and used this dataset to successfully
      train a Support Vector Machine (SVM) model that predicts an additional
      approximately 10,000 unique HNF4alpha-binding sequences; we also identify new
      rules for HNF4alpha DNA binding. We performed expression profiling of an
      HNF4alpha RNA interference knockdown in HepG2 cells and compared the results to a
      search of the promoters of all human genes with the PBM and SVM models, as well
      as published genome-wide location analysis. Using this integrated approach, we
      identified approximately 240 new direct HNF4alpha human target genes, including
      new functional categories of genes not typically associated with HNF4alpha, such
      as cell cycle, immune function, apoptosis, stress response, and other cancer
      related genes. CONCLUSION: We report the first use of PBMs with a full-length
      liver-enriched transcription factor and greatly expand the repertoire of
      HNF4alpha-binding sequences and target genes, thereby identifying new functions
      for HNF4alpha. We also establish a web-based tool, HNF4 Motif Finder, that can be
      used to identify potential HNF4alpha-binding sites in any sequence.

PMID- 20054871
TI  - Transient elastography in nonalcoholic fatty liver disease: making sense of
      echoes.

PMID- 20054870
TI  - Progenitor-derived hepatocellular carcinoma model in the rat.
AB  - Human hepatocellular carcinoma (HCC) is a heterogeneous disease of distinct
      clinical subgroups. A principal source of tumor heterogeneity may be cell type of
      origin, which in liver includes hepatocyte or adult stem/progenitor cells. To
      address this issue, we investigated the molecular mechanisms underlying the fate
      of the enzyme-altered preneoplastic lesions in the resistant hepatocyte (RH)
      model. Sixty samples classified as focal lesions, adenoma, and early and advanced
      HCCs were microdissected after morphological and immunohistochemical evaluation
      and subjected to global gene expression profiling. The analysis of progression of
      the persistent glutathione S-transferase (GSTP)(+) focal lesions to fully
      developed HCC showed that approximately 50% of persistent nodules and all HCCs
      expressed cytokeratin 19 (CK19), whereas 14% of remodeling nodules were CK19(+).
      Unsupervised hierarchical clustering of the expression profiles also grouped the
      samples according to CK19 expression. Furthermore, supervised analysis using the
      differentially expressed genes in each cluster combined with gene connectivity
      tools identified 1308 unique genes and a predominance of the AP-1/JUN network in
      the CK19(+) lesions. In contrast, the CK19-negative cluster exhibited only
      limited molecular changes (156 differentially expressed genes versus normal
      liver) consistent with remodeling toward differentiated phenotype. Finally,
      comparative functional genomics showed a stringent clustering of CK19(+) early
      lesions and advanced HCCs with human HCCs characterized by poor prognosis.
      Furthermore, the CK19-associated gene expression signature accurately predicted
      patient survival (P < 0.009) and tumor recurrence (P < 0.006). CONCLUSION: Our
      data establish CK19 as a prognostic marker of early neoplastic lesions and
      strongly suggest the progenitor derivation of HCC in the rat RH model. The
      capacity of CK19-associated gene signatures to stratify HCC patients according to
      clinical prognosis indicates the usefulness of the RH model for studies of
      stem/progenitor-derived HCC.

PMID- 20054872
TI  - Immune thrombocytopenic purpura in a 5-month-old female with rotavirus infection.

PMID- 20054873
TI  - Through the looking glass: publishing in a journal in another language or another
      country.

PMID- 20054875
TI  - Atypical antipsychotics and anorexia nervosa: a review.
AB  - BACKGROUND: There is currently mixed opinion regarding the value of using
      atypical antipsychotics to treat anorexia nervosa (AN). AIMS: To evaluate the
      literature on the use of atypical antipsychotics in AN. METHOD: A review of all
      studies and clinical guidelines published before September 2009 involving use of
      an atypical antipsychotic in patients with AN. Analysis is by narrative
      synthesis. RESULTS: Forty-three publications or study protocols were found,
      including four randomized-controlled trials, five open-label trials and 26 case
      reports. The most studied drugs were olanzapine, quetiapine and risperidone.
      Atypical antipsychotics appear safe and there is some evidence of positive
      effects on depression, anxiety and core eating disordered psychopathology in
      patients with anorexia nervosa. Currently there is insufficient evidence to
      confirm atypical antipsychotics enhance weight gain in this setting. CONCLUSIONS:
      Further high quality evidence is needed in this area in order to provide
      practical guidance to clinicians. However, the main challenge is to persuade
      adequate numbers of AN patients to participate in research trials.

PMID- 20054876
TI  - Towards an ecology of eating disorders: creating sustainability through the
      integration of scientific research and clinical practice.
AB  - The field of eating disorders is currently at a crossroads and faces important
      challenges of sustainability. These challenges include problems with the current
      diagnostic classification of eating disorders and the divide between scientific
      research and clinical practice. If not addressed, there is a danger that the
      field will fail to evolve adaptively, risking increased stagnation and reduced
      relevance. To meet these challenges, researchers and clinicians must work toward
      a more holistic ecology of eating disorders based on the interaction of theory,
      research and practice. The present paper proposes six steps towards increased
      sustainability based on developing clinically relevant diagnosis, using
      systematic quality assurance, expanding the scope of treatment research and the
      definition of evidence, promoting therapist development, as well as stimulating
      diversity and discourse. If we rise to the occasion and face these challenges,
      then we will be better equipped to meet the evolving needs of clinicians,
      researchers, and most importantly patients.

PMID- 20054877
TI  - Predicting the weight gain required for recovery from anorexia nervosa with
      pelvic ultrasonography: an evidence-based approach.
AB  - Target weights are an arbitrary means of determining return to physical health in
      patients with anorexia nervosa (AN) and lack reliability and validity.
      Transabdominal pelvic ultrasound scanning (U/S) offers a more objective method of
      ascertaining physical well being by the ability to determine reproductive
      maturity. This study aimed to explore the correlations between the maturity
      grading on pelvic U/S and weight for height (WfH) ratios and body mass index
      (BMI) percentiles. Ultrasound studies were performed in 72 female adolescents
      (aged 11-17 years at intake) with AN. Scans were graded for maturity using
      published parameters of pelvic maturity and compared with the patient's WfH ratio
      and BMI percentile. In our sample was a wide variation of WfH ratios and BMI
      percentiles at each grade of maturity. This supports the view that arbitrary
      targets for weight, WfH ratio or BMI percentile are likely to be unnecessarily
      high for some patients and too low for others. We recommend that targets be based
      upon baseline pelvic U/S grading and follow-up scanning.

PMID- 20054878
TI  - Psychometric evaluation of a Brazilian version of the impact of weight on quality
      of life (IWQOL-Lite) instrument.
AB  - PURPOSE: The impact of weight on quality of life (IWQOL-Lite) is a self
      administered instrument that assesses quality of life in obesity. It is composed
      of 31 items and five domains (physical function, self-esteem, sexual life, public
      distress, and work). The aim of the present study was to evaluate reliability
      (test-retest), internal structure, construct validity and discriminant validity.
      METHODS: IWQOL-Lite scores were obtained from 89 people in a Weight Watchers
      institution (clinical sample) and 156 community volunteers (community sample).
      The participants were selected based on the same criteria: gender (female) and
      age (> 24 years), except for BMI. The community sample also completed the SF-36,
      a generic measure of health-related quality of life. RESULTS: The Brazilian IWQOL
      Lite demonstrated good test-retest reliability, internal consistency,
      discriminative validity and convergent validity. CONCLUSIONS: The IWQOL-Lite is
      the first specific instrument validated in Brazil for assessing quality of life
      in obesity. The results reveal that IWQOL-Lite is an instrument with good
      psychometric properties. Nevertheless, in some cases results were dissimilar to
      those reported in earlier studies using the original American English.

PMID- 20054879
TI  - Brachial-ankle pulse wave velocity and cardiovascular risk factors in the non
      diabetic and newly diagnosed diabetic Chinese: Guangzhou Biobank Cohort Study
      CVD.
AB  - BACKGROUND: Increased arterial stiffness is an important cause of cardiovascular
      disease (CVD). We examined determinants of arterial stiffness in subjects across
      strata of glycaemic status. METHODS: A total of 1249 subjects from a sub-study of
      the Guangzhou Biobank Cohort Study (GBCS-CVD) had brachial-ankle pulse wave
      velocity (baPWV) measured by automatic oscillometric method. Major cardiovascular
      risk factors including glycosylated haemoglobin A1c (HbA(1c)), high sensitivity C
      reactive protein (hsCRP), fasting triglyceride, low- and high-density lipoprotein
      cholesterol and both fasting and post 2-h oral glucose-load glucose, systolic and
      diastolic blood pressure were assessed. RESULTS: In all, 649, 479 and 121
      subjects were classified into normoglycaemia, impaired glucose metabolism (IGM)
      and newly diagnosed diabetes groups, respectively. Both age and systolic blood
      pressure were significantly associated with increased baPWV in all three groups
      (all p < 0.001). In both normoglycaemic and IGM groups, hsCRP and HbA(1c) were
      positively associated with baPWV (p from 0.04 to < 0.001), whereas current
      smoking and triglyceride were associated with baPWV in the normoglycaemic and IGM
      group, respectively (p = 0.04 and 0.001). No gender difference in baPWV was
      observed in the normoglycaemic or IGM groups. However, in the newly diagnosed
      diabetes group, men had higher baPWV than women (p = 0.01). CONCLUSIONS: In the
      normoglycaemic and IGM subjects, after adjusting for age, blood pressure and
      other confounders, increasing HbA(1c) was associated with increased baPWV,
      suggesting a pathophysiological role of chronic glycaemia that can contribute to
      vascular disease risk in persons without diabetes.

PMID- 20054880
TI  - Quadricuspid pulmonary valve diagnosed by cardiac magnetic resonance.

PMID- 20054881
TI  - The Francisella tularensis pathogenicity island encodes a secretion system that
      is required for phagosome escape and virulence.
AB  - Francisella tularensis causes the human disease tularemia. F. tularensis is able
      to survive and replicate within macrophages, a trait that has been correlated
      with its high virulence, but it is unclear the exact mechanism(s) this organism
      uses to escape killing within this hostile environment. F. tularensis virulence
      is dependent upon the Francisella pathogenicity island (FPI), a cluster of genes
      that we show here shares homology with type VI secretion gene clusters in Vibrio
      cholerae and Pseudomonas aeruginosa. We demonstrate that two FPI proteins, VgrG
      and IglI, are secreted into the cytosol of infected macrophages. VgrG and IglI
      are required for F. tularensis phagosomal escape, intramacrophage growth,
      inflammasome activation and virulence in mice. Interestingly, VgrG secretion does
      not require the other FPI genes. However, VgrG and other FPI genes, including
      PdpB (an IcmF homologue), are required for the secretion of IglI into the
      macrophage cytosol, suggesting that VgrG and other FPI factors are components of
      a secretion system. This is the first report of F. tularensis FPI virulence
      proteins required for intramacrophage growth that are translocated into the
      macrophage.

PMID- 20054882
TI  - The CsdA cysteine desulphurase promotes Fe/S biogenesis  by recruiting Suf
      components and participates to a new  sulphur transfer pathway by recruiting CsdL
      (ex-YgdL),  a ubiquitin-modifying-like protein.
AB  - Cysteine desulphurases are primary sources of sulphur that can eventually be used
      for Fe/S biogenesis or thiolation of various cofactors and tRNA. Escherichia coli
      contains three such enzymes, IscS, SufS and CsdA. The importance of IscS and SufS
      in Fe/S biogenesis is well established. The physiological role of CsdA in
      contrast remains uncertain. We provide here additional evidences for a functional
      redundancy between the three cysteine desulphurases in vivo. In particular, we
      show that a deficiency in isoprenoid biosynthesis is the unique cause of the
      lethality of the iscS sufS mutant. Moreover, we show that CsdA is engaged in two
      separate sulphur transfer pathways. In one pathway, CsdA interacts functionally
      with SufE-SufBCD proteins to assist Fe/S biogenesis. In another pathway, CsdA
      interacts with CsdE and a newly discovered protein, which we called CsdL,
      resembling E1-like proteins found in ubiquitin-like modification systems. We
      propose this new pathway to allow synthesis of an as yet to be discovered
      thiolated compound.

PMID- 20054884
TI  - Personal reflections on a sensitive subject.

PMID- 20054883
TI  - Add H1N1 preparations to the start of the school year.

PMID- 20054885
TI  - CA-125 in the Diagnosis of Pulmonary Tuberculosis.

PMID- 20054886
TI  - Prevalence of Coxiella burneti antibodies in wild ruminants in kaveeany zoo,
      kosice, Eastern Slovakia.
AB  - Coxiella burnetii is an obligate intracellular agent that causes Q fever in
      humans and animals. The most important reservoirs of C. burnetii in nature are
      small wild rodents, but infection was also demonstrated in other animals,
      including ruminants. Samples of blood were obtained from 4 mouflons, 60 fallow
      deer, 9 Cameroun goats, 8 Carpathian goats, and 8 Cameroun sheep living in a zoo.
      Antibodies to phase I and phase II C. burnetii antigens were determined in sera
      by ELISA. Antibody titres were detected in the range 1:100-1:200. The serum
      prevalence of phase II and phase I antibodies to C. burnetii antigens was 25% and
      0% in mouflons, 70% and 0% in goats, 37.5% and 12.5% in sheep and 28.3% and 5% in
      fallow deer, resp. Serologic diagnosis of Q fever in animals can be difficult.
      Some animals may shed C. burnetii and pose a risk for infection prior to the
      development of antibodies, and some infected animals never seroconvert. The
      employed ELISA test is a very sensitive assay for C. burnetii, but it is also a
      labour intensive method and therefore not routinely available.

PMID- 20054887
TI  - [Abstracts of the 82nd General Meeting of the Japanese Leprosy Association of the
      21st Co-Medical Meeting. May 13-15, 2009. Izumo, Japan].

PMID- 20054888
TI  - [Abstracts of the 49th Joint Annual Meeting of the Japanese Society of Neurology.
      May 15-17, 2008. Yokohama, Japan].

PMID- 20054889
TI  - [Abstracts of the 113th Annual Meeting of the Japanese Ophthalmological Society.
      April 16-19, 2009. Tokyo, Japan].

PMID- 20054890
TI  - Re: The Brunelli square acetabular cup.

PMID- 20054891
TI  - [Abstracts of the 56th Meeting of the Japanese Society of Clinical Pathology.
      August 26-29, 2009. Sapporo, Japan].

PMID- 20054892
TI  - [Abstracts of the 84th Annual Meeting of the Japanese Society for Tuberculosis.
      July 2-3, 2009. Sapporo, Japan].

PMID- 20054893
TI  - [Abstracts of the 49th Annual Meeting of the Japanese Respiratory Society. June
      12-14, 2009. Tokyo, Japan].

PMID- 20054894
TI  - [Abstracts of the 52nd Annual Meeting of the Japanese Society of Nephrology. June
      3-5, 2009. Yokohama, Japan].

PMID- 20054895
TI  - [Abstracts of the 97th Annual Meeting of the Japanese Urological Association.
      April 16-19, 2009. Okayama, Japan].

PMID- 20054897
TI  - [Abstracts of the 68th Annual Meeting of the Japanese Radiological Society. April
      16-19, 2009. Yokohama, Japan].

PMID- 20054896
TI  - [Abstracts of the 110th Congress of the Japanese Society of Otolaryngology. May
      14-16, 2009. Tokyo, japan].

PMID- 20054898
TI  - [Abstracts of the 22nd Annual Meeting of the Association for Rapid Method and
      Automation in Microbiology. July 4, 2009. Saga, Japan].

PMID- 20054899
TI  - Proteomics.

PMID- 20054900
TI  - [Abstracts of the 45th Autumn Meeting of the Japanese Radiological Society.
      October 29-31, 2009. Wakayama, Japan].

PMID- 20054901
TI  - [Abstracts of the 71st Annual Meeting of the Japanese Society of Hematology.
      October 23-25, 2009. Kyoto, Japan].

PMID- 20054903
TI  - [Abstracts of the 49th Annual Meeting of the Japanese Society of Nuclear
      Medicine. October 1-3, 2009. Asahikawa, Japan].

PMID- 20054902
TI  - [Abstracts of the 59th General Meeting of the Japanese Society of Allergology.
      October 29-31, 2009.  Akita, Japan].

PMID- 20054904
TI  - [Abstracts of the 39th Easter/Western Regional Meeting, Japanese Society of
      Nephrology. October 2009. Japan].

PMID- 20054905
TI  - [Abstracts of the 93rd Congress of the Japanese Society of Legal Medicine. May 13
      15, 2009. Osaka, Japan].

PMID- 20054906
TI  - [Abstracts of the 48th Annual Meeting of the Japanese Society of Nuclear
      Medicine. October 24-26, 2008. Chiba, Japan].

PMID- 20054907
TI  - [Abstracts of the 51st Annual Meeting of the Japanese Society of Child Neurology.
      May 28-30, 2009. Yonago, Japan].

PMID- 20054908
TI  - [Regional Meeting of the Japanese Radiological Society, 2007. Abstracts].

PMID- 20054909
TI  - [Abstracts of the 50th Annual meeting of the Japanese Society of Neurology. May
      20-22, 2009. Sendai, Japan].

PMID- 20054910
TI  - Chest pain and dysponoea resulting from a perforated duodenal ulcer.

PMID- 20054912
TI  - Reviews of environmental contamination and toxicology. Preface.

PMID- 20054913
TI  - Resolutions address random-source animals, swine disease.

PMID- 20054914
TI  - Pigs, people and now pets.

PMID- 20054915
TI  - Ohio voters OK board overseeing livestock care standards.

PMID- 20054916
TI  - Halters could control cattle without fences.

PMID- 20054918
TI  - [Apoptosis--programmed cell death. Zagreb May 3 2009].

PMID- 20054917
TI  - HSUS calls for more rules after calf abuse allegations.

PMID- 20054919
TI  - Intervertebral disc degeneration.
AB  - Disc degeneration in the human spine is a complex phenomenon characterised by
      biochemical change in the nucleus pulposus and inner annulus and the formation of
      clefts and fissures radiating from the central area of the disc towards the
      periphery. In addition, and probably independent of these phenomena, discrete
      defects in the outer annular attachement are seen which are likely to be due to
      mechanical stress and failure. The presence of stress tears in disc tissue and
      their failure to heal can initiate or accelerate the degeneration of the central
      component of the intervertebral disc. We postulate that discogenic pain may be
      linked to damage to the outer portion of the annulus fibrosus. Although it would
      seem logical to assume that discs with sustained high intradiscal pressure would
      be more prone to pain referred in the outer annular layers because of higher
      tensile strain, analysis of prospective studies has failed to confirm a
      relationship between typical pain reproduction at discography and high pressure
      values. It is concluded that, at present, the only consistent morphological
      changes present in patients with pain reproduction at discography are the
      presence of various annular defects involving the outer layers. Whether nerve
      ingrowth during attempts at repair of these defects is a consistent feature
      remains to be established.

PMID- 20054921
TI  - Cervical spine locking plate: in vitro biomechanical testing.
AB  - The AO cervical spine locking plate (CSLP) for anterior subaxial fixation was
      recently received increasing clinical acclaim, yet to date the in vitro
      mechanical properties of this implant have not been reported. To determine the in
      vitro biomechanical properties of this device, five fresh human cadaver cervical
      spines were subjected to nondestructive testing in flexion and torsion in three
      stages: stage 1: intact spine; stage 2: destabilized spine; stage 3: destabilized
      spine with CSLP. Stage 3 specimens were also subjected to large angular
      displacement testing to assess the integrity of the fixation. In flexion, mean
      spinous process displacement was 1.21 mm for stage 1, 3.19 mm for stage 2, and
      1.37 mm, for stage 3. Mean torsional stiffness was 2.86 Nm/degree in stage 1,
      1.82Nm/degree in stage 2, and 2.20Nm/degree in stage 3. Large angular
      displacement testing in stage 3 resulted in screw loosening from the bone in two
      specimens; no screw plate loosening occurred. In our severely destabilized in
      vitro model, the CSLP restored flexion stability but not rotational stability.
      This suggests that supplemented bracing or fixation may be required to restore
      torsional stability.

PMID- 20054920
TI  - Abnormal stress concentrations in lumbar intervertebral discs following damage to
      the vertebral bodies: a cause of disc failure?
AB  - The purpose of this investigation was to test the hypothesis that damage to a
      lumbar vertebral body can lead to abnormal stress concentrations in the adjacent
      intervertebral discs. Twenty-three cadaveric lumbar "motion segments", from
      persons who had died aged between 19 and 87 years, were subjected to substantial
      compressive loading while in the neutral, lordotic and flexed "postures". During
      the loading period, a miniature pressure transducer was pulled through the disc
      along its mid-sagittal diameter and graphs of horizontal and vertical compressive
      stress against distance were obtained. Measurements were repeated after each
      motion segment had been compressed up to the point of mechanical failure: at this
      point the vertebral bodies suffered minor damage to the trabecular arcades, and
      sometimes to the end-plate, but the structure remained essentially intact and
      motion segment height was reduced by only 1%-2%. After damage, the stress in the
      nucleus and anterior annulus fell by about 30%, and high stress peaks appeared in
      the inner posterior annulus. These changes were more pronounced in lordotic
      posture and less pronounced in flexion. The youngest discs showed the smallest
      changes. It is concluded that minor compressive damage to the vertebral body can
      lead to high stress concentrations in the posterior annulus. Since the vertebral
      body is the "weak link" of the lumbar spine, this may be a frequent precipitating
      cause of isolated disc failure in living people.

PMID- 20054922
TI  - Postoperative lumbar discitis.
AB  - We analysed 13 cases of lumbar disc infection following surgical discectomy. Two
      groups of patients were identified. The six patients in group A reported that the
      initial symptoms of discitis had appeared a mean of 15 days after surgery; on
      average, antibiotic treatment was started 31 days following operation and
      continued for 62 days, and symptoms regressed after 3.9 months. Four patients
      showed moderate changes, while two had extensive osteolytic lesions of one or
      both vertebral bodies adjacent to the involved disc. In the 7 cases in group B,
      discitis was suspected a mean of 5 days and antibiotics were initiated a mean of
      8 days following surgery; on average, symptoms regressed 1.8 months after
      operation. Only four patients showed vertebral radiographic changes and none had
      marked destructive lesions. In both groups erythrocyte sedimentation rate
      exceeded 70 mm/h in cases in which discitis was suspected. Tomograms and magnetic
      resonance studies were the most diagnostic imaging studies in the initial stages
      of the disease. All patients obtained satisfactory clinical results at the last
      follow-up. Careful observation of the early postoperative clinical course usually
      allows detection of disc space infection. Early and adequately prolonged
      antibiotic treatment may shorten the course of the disease and avoid extensive
      osteolytic vertebral lesions.

PMID- 20054923
TI  - Radical and debridement surgery for tuberculosis of the spine in children: a
      preliminary analysis of results from a 17-year prospective study.
AB  - We reviewed 80 children (39 male, 41 female) with tuberculosis of the spine, all
      of whom were subjects of the Medical Research Council Working Party's study in
      Hong Kong. Forty-seven children were treated with radical surgery and the
      remaining 33 with debridement surgery. The mean ages at operation for radical
      surgery and debridement were 7.6 and 5.1 years respectively, and the mean post
      operative follow-up was 15.3 and 19.7 years respectively. The clinical and
      radiological data obtained pre-operatively, 6 months, 1 year and 5 years post
      operatively, and at final follow-up were analysed. Neither patients treated with
      radical nor those treated with debridement surgery had pain or neurological
      deficit at final follow-up. In the radical surgery group, there was a reduction
      of the angles of kyphosis and deformity following surgery, which was maintained
      throughout subsequent follow-up years. However, in the debridement surgical
      group, there was an increase in the angles of kyphosis and deformity following
      surgery, which showed a tendency to spontaneous correction in the long term. In
      this study we did not observe any progressive kyphosis in either group.

PMID- 20054925
TI  - Imbalance of electromyographic activity and physical rehabilitation of patients
      with idiopathic scoliosis.
AB  - In order to monitor changes in postural performance capacity in patients with
      idiopathic scoliosis after an intensive in-patient Schroth rehabilitation
      programme lasting several weeks, we undertook electromyographic investigations in
      316 patients with a mean age of 20 years (range 8-76 years) and a mean Cobb
      curvature angle of 38.2 degrees (range 10 degrees-147 degrees). Electromyographic
      activity was recorded by means of surface electrodes in the thoracic and lumbar
      region at the level of the apical vertebra, paravertebrally on both sides of the
      erector spinae muscle during trunk lifting from the prone position. Two hundred
      and fifty-nine recordings without artefacts were evaluated. Significant
      reductions in muscle activity of 6.85% in the thoracic convex region (P < 0.05)
      and of 14.2% (P < 0.001) on the lumbar convex side were found. The activity
      quotient (convesx/concave) was reduced by 11.99% (P<0.001) in the thoracic region
      and by 7.91% (P<0.01) in the lumbar region. These findings confirm the
      improvement of postural performance capacity after an intensive in-patient
      Schroth rehabilitation programme. As the imbalance of electromyographic activity
      may be influenced by scoliosis-specific exercises leading to a highly significant
      reduction of the Cobb angle, it is assumed to be secondary to the development of
      the scoliotic curve and may not be a primary factor in the aetiology of
      idiopathic scoliosis.

PMID- 20054924
TI  - Spinal growth and progression of adolescent idiopathic scoliosis.
AB  - The spinal growth in scoliotic segments (T4-L4) of 110 girls with untreated
      idiopathic scoliosis was measured from two successive radiographs taken at a mean
      interval of 1.1 years. At the first visit the mean age of the patients was 14
      years (range 11-16 years), the mean magnitude of the major curves 24 degrees
      (range 9 degrees-38 degrees) and that of the minor curves 14 degrees (range 2
      degrees-38 degrees). Spinal growth was most rapid at the age of 11-12 years. The
      progression of the curves (major plus minor) correlated with the spinal growth (r
      = 0.384). The greater the initial curves were, the stronger the correlation was
      between the spinal growth and the progression of the curves (r = 0.046-0.639),
      and the correlation was more significant in thoracic scoliosis (r = 0.560) than
      in thoracolumbar and lumbar scoliosis (r = 0.152).

PMID- 20054926
TI  - Fracture of the spine, spinal epidural haematoma and spondylitis. Report of one
      case and review of the literature.
AB  - We report the case of a patient suffering from spinal epidural haematoma and
      thoracic spinal fracture, and from ankylosing spondylitis. Fourteen cases of
      spinal epidural haematoma in association with ankylosing spondylitis have been
      reported in the literature, 12 of them at a cervical level. Spinal epidural
      haematoma found in patients suffering from ankylosing spondylitis share the same
      clinical picture as other haematomas, the notion of time being the main feature.
      Serious neurological complications caused the death of five patients. The case we
      report is singular for its thoracic localization and two attacks of total
      paralysis both followed by spontaneous and complete recovery. Today, MRI is the
      best method to reach a clear and reliable diagnosis. Widespread use of MRI will
      certainly increase the number of diagnoses made. Our patient underwent operation
      including osteosynthesis using Cotrel-Dubousset instrumentation. This enabled him
      to resume his professional activities only 30 days after his accident.

PMID- 20054927
TI  - Laminectomy combined with posterolateral stabilisation: a muscle-sparing approach
      to the lumbosacral spine.
AB  - We report our experience with a technique of midline posterior decompression in
      combination with the Wiltse muscle splitting approach for posterolateral spinal
      fusion and pedicle screw fixation. The technique is suitable for cases of lumbar
      spinal stenosis and disc herniation where stabilisation is required and has
      significant advantages over other reported methods. This combined approach has
      been used in 52 patients since 1990 with no complications from the approach
      itself.

PMID- 20054928
TI  - Lumbar disc prosthesis. Surgical technique, indications and clinical results in
      22 patients with a minimum of 12 months follow-up.
AB  - Twenty-two patients with 29 lumbar disc prosthesis have been reviewed clinically
      and radiologically with a minimum of 12 months follow-up. The first operation in
      France with the SB Charity model was carried out in January 1989 with the help of
      the German authors Schellnack and Buttner. The surgical technique consists of an
      anterior extraperitoneal approach with the patient in a supine and hyperlordotic
      position and must be very precise. The indications are very rare. At the moment,
      we only consider the prosthesis as an alternative to an arthrodesis in young
      patients with good-quality bone. We limit the indication to cases where fusion in
      situ is to be avoided: degenerative disease with collapsed disc, failed backs and
      instability at a maximum of one or two levels. The immediate results are
      encouraging, and no loosening of the prosthesis or osteolysis at the bone
      prosthesis interface has been noticed in patients with 2 or more years follow-up.
      The segmental mobility still remains in bending and flexion/extension and is
      demonstrated by dynamic X-rays. Because we do not know the long-term results of
      implantation of the prosthesis, it must continue to be a rare procedure and the
      patient must be informed that in case of failure, fusion by a posterior or
      anterior approach may be necessary and is always possible.

PMID- 20054929
TI  - The indications and principles of correction of post-traumatic deformities.
AB  - Post-traumatic malposition of the spine usually results in inadequate
      conservative treatment or incorrect surgical therapy. The main indication for
      secondary reconstructive measures in pain. Besides the predominant vertebragenic
      causes, neuropathic forms may be combined in spinal cord damage. Secondary
      neurological damage or progressive neurological deficits are combined with
      persistent spinal compression or increasing (mostly kyphotic) malpositions. The
      objective of the surgical treatment is to correct the malposition with
      reprofiling the spine and restoration of the stability of the axis organ.
      Attention must be paid to primary or secondary spinal lesions, since additional
      neurological lesions can be provoked when the strategy is wrong, and concomitant
      or prior neurosurgical interventions may become necessary. Almost exclusively,
      the objective of our reconstructive measures with reprofiling of the injured
      spine avoiding damage to healthy movement segments can be achieved only by a
      combined ventral and dorsal operation. The crucial shortcomings result from the
      first treatment. Acceptable treatment results can only be expected in both first
      and secondary treatment of spinal cord injuries when the following factors are
      taken into consideration: (1) pretherapeutic definition of the injury pattern;
      (2) the functional anatomy of the spine (load sharing and tension band
      principle); (3) mastery of all approaches (dorsal, dorsolateral, ventral) and the
      instrumentation.

PMID- 20054930
TI  - New inflammation markers for early detection of spondylodiscitis.
AB  - Even today a significant feature of spondylodiscitis is the long interval between
      the onset of symptoms and the establishment of the diagnosis (on average 6.4
      months in our study). In order to improve early detection of spinal infections,
      new markers of inflammation were determined in patients with spondylodiscitis.
      Neopterin is produced by macrophages after their activation by T-lymphocytes,
      polymorphonuclear neutrophil (PMN) elastase is set free by activated
      granulocytes. Erythrocyte sediment rate (ESR) showed the highest sensitivity of
      all determined inflammation markers, but reached only a poor diagnostic
      specificity. The sensitivity of the white blood cell count was poor. C-reactive
      protein (CRP) and neopterin reached a sensitivity of 75% each in spondylodiscitis
      and had a good diagnostic specifity. Sensitivity of PMN elastase reached 67%.
      Contrary to ESR the new inflammation markers were also helpful in the following
      up of treated spondylodiscitis. PMN elastase showed quickest normalization of all
      inflammation parameters. For early detection of spondylodiscitis and clinical
      follow up we recommed combined determinations of CRP, neopterin and PMN elastase.

PMID- 20054931
TI  - Adolescent disc protrusions. A long term follow-up of chymopapain therapy.
AB  - The management of adolescent disc protrusions by chemonucleolysis has received
      little attention in the literature, and reports of the long-term outcome are
      lacking. Between May 1978 and July 1986 42 patients between the ages of 13 and 19
      years with radiologically proven lumbar disc protrusions were treated at this
      institution with chymopapain. They were followed prospectively for 1 year, and
      the procedure was successful in 27 patients (64%). Of the 15 patients in whom the
      treatment failed, 11 underwent subsequent surgical discectomy, successful in 10,
      giving an overall treatment success rate of 37/42 (88%) at 1 year. The patients
      were contacted by telephone and questionnaire at a minimum of 5 years after
      treatment (mean 8.5 years), and full replies were obtained from 39/42 (93%). The
      long-term outcome was good or excellent in 82%. A history of injury, and the
      demonstration by MRI or discography of disc degeneration at more than one level
      was associated with a reduced success rate both at 1 year and in the long term.
      We conclude that there are no long-term ill effects of chemonucleolysis with
      chymopapain on the adolescent disc. It is a useful procedure that is well
      tolerated and we have no reservations about its use.

PMID- 20054932
TI  - Solid fusion vs. non-union in long-term follow-up of in situ fusion without
      internal fixation in symptomatic spondylolisthesis in young patients.
AB  - A clinical and radiological long-term follow-up study is presented of 175
      patients under the age of 20 years operated on for symptomatic isthmic
      spondylolisthesis of L5. The mean observation time was 15 years (range 5-30
      years). There were 89 female and 86 male patients; mean age at operation was 14.8
      years. Posterior fusion was carried out in 112 cases, posterolateral fusion in 60
      and anterior fusion in 3; a concomitant laminectomy was performed in 34 cases.
      One segment (L5-S1) was fused in 54 patients, two segments (L4-S1) in 104, and
      three segments (L3-S1) in 17. Autogenous cortico-spongeous bone was used in 119
      cases and free periosteal grafts in 56. At follow-up, solid bony fusion was found
      in 145 patients; 30 patients (17.1%) had non-union. The data for these two groups
      were compared statistically. The frequency of nonunion was significantly higher
      after posterior than after posterolateral fusion (P< 0.05), in two-level fusions
      than in one-level fusions (P = 0.003), and in cases where periosteal rather than
      cortico-spongeous bone grafts had been used (P<0.01). The posterior fusion
      technique using periosteal grafts gave the highest rate of non-unions, whereas
      the posterolateral technique with cortico-spongeous grafts gave the highest rate
      of successful fusions (P < 0.001). Non-union occurred significantly more often in
      cases of grade I slip (36%) than in cases of grade II (7%), III (8%) or IV slip
      (0%). The higher frequency of nonunions in grade I slips was associated with more
      frequent use of the posterior fusion technique in cases of minor or moderate
      grades of slip. The duration of postoperative bed rest or duration of
      immobilization in a corset had no statistically significant influence on fusion
      rate. The rate of non-union had no statistically significant association with the
      long-term clinical result. Postoperative pain symptoms, however, lasted longer in
      non-union patients (mean 14.2 months) than in successfully fused patients (mean
      4.5 months; P<0.01). The results show the benign nature of the condition, which
      seems to be a self-limiting process leading to stabilization of the affected
      segment. The posterolateral fusion technique using autogenous cortico-spongeous
      bone grafts is recommended as the method of choice for most cases.

PMID- 20054933
TI  - Idiopathic scoliosis: prognostic value of the profile.
AB  - A study was undertaken to establish the significance of the sagittal shape of the
      spine in 138 consecutively treated girls with early idiopathic thoracic
      scoliosis. All were treated in a Boston brace. Two groups were formed: group I
      consisted of 120 girls whose scoliosis remained stable in the brace, group II of
      18 girls who required a spinal fusion for progressive curves despite the brace.
      For each spine, the orientation of each vertebra to the horizontal in the
      sagittal plane was measured on the earliest lateral radiogram, taken when the
      anterior curve still had a Cobb angle of less than 20 degrees. A significant
      difference in spinal profile was found between the two groups. Progressive curves
      showed a more retroverted orientation of mid- and high thoracic vertebrae than
      stable curves.

PMID- 20054934
TI  - Pull-out strength of sacral implants using Cotrel-Dubousset fixation devices.
AB  - Our aim was to determine the bone structure of the sacrum and the optimum
      location in the sacrum for the insertion of lumbosacral screws in osteosynthesis.
      Anatomical tests were performed on mortuary specimens at the Medical School in
      Nice, France, on frozen sections of sacrum and in computed tomographic (CT)
      sections with 3-dimensional reconstruction. Density assessment of different
      structures from the first and second sacral vertebrae (S1, S2) was performed and
      expressed in Hounsfield units. The ala and the lateral part of S1 contained
      yellow marrow forming a fatty mass bounded by the cortex of the sacroiliac joint
      at the linea terminalis and by the cancellous bone in the pedicles and the body
      of S1 and S2. These studies were undertaken prior to the experimental tests. The
      experimental tests were made using Cotrel-Dubousset instrumentation to determine
      the pull-out strength of sacral screws with a 7-mm diameter by assessing pull-out
      strengths of paired screws arranged either unilaterally with one screw in S1 and
      one in S2 or symmetrically to the left and right in S1. The devices demonstrating
      the best pull-out strength were the "corporopedicular" screw in S1 and the caudal
      lateral oblique screw in S1 passing through the sacroiliac joint. The paired
      screws with the best pull-out strength were those which included a
      corporopedicular screw in S1.

PMID- 20054935
TI  - Viscoelasticity of the alar and transverse ligaments.
AB  - The occipito-atlanto-axial joint is the most complex one of the human spine.
      Traumatic or inflammatory lesions in this region may lead to instability and
      neurological symptoms of clinical importance. This study reports the results of
      anatomical and biomechanical examination of 13 human upper cervical spine
      specimens and focuses on the viscoelastic behavior of the alar and transverse
      ligaments. Non-destructive tensile testing was performed on a uniaxial testing
      machine with 25 alar and 11 transverse ligaments at three different load rates of
      0.1 mm/s, 1.0 mm/s, and 10.0 mm/s. The ligaments were further tested for
      relaxation over 300s. Each ligament exhibited an initial neutral zone in which no
      tensile force could be measured during cyclic testing. This neutral zone was more
      significant in the alar ligaments than in the transverse ligaments with respect
      to the measured in situ length of the ligaments (11.2 vs 18.1 mm on average).
      Increasing axial deformation led to increased load in all ligaments. Hysteresis,
      i.e., the energy loss exhibited by viscoelastic material subjected to loading and
      unloading cycles, increased with higher displacement rates and higher tensile
      forces. In neutral position the alar ligaments were lax in all specimens. During
      axial rotation both alars tightened. Ligamentous resistance increased as the end
      of the range of motion (ROM) was approchaed during rotation. The neutral zone
      explains the laxity of the ligaments in midposition and allows mobility of the
      upper cervical spine with minimum expenditure of muscular energy. The ligaments
      become stiffer under higher loads and therefore contribute to a limitation of the
      ROM in the occipitio-atlanto-axial joint.

PMID- 20054936
TI  - In vitro investigations of internal fixation systems of the upper cervical spine.
      I. Stability of the direct anterior screw fixation of the odontoid.
AB  - Fresh odontoid fractures of types II and III and in some cases nonunions of the
      odontoid can be repaired by direct anterior screw fixation preserving C1-C2
      motion. The goal of this experimental study was to investigate the biomechanical
      stability of the fragment achieved by this direct odontoid osteosynthesis
      according to Bohler. Sixteen human C1-C2 segments with fractures of type II or
      type III were biomechanically tested in vitro under standardized conditions.
      Flexion and extension moments, anterior and posterior shear forces were applied,
      and the motion of the refixed odontoid fragment relative to C2 was determined.
      The results show that direct screw fixation of the odontoid under the
      experimental conditions provides sufficient stability for the dens fragment.

PMID- 20054937
TI  - In vitro investigations of internal fixation systems of the upper cervical spine.
      II. Stability of posterior atlanto-axial fixation techniques.
AB  - Unstable C1-C2 segments are generally treated surgically. Depending on the
      indication a direct screw fixation of the odontoid or a C1-C2 arthrodesis is a
      possible technique. In this experimental in vitro study the three different
      atlantoaxial fusion techniques by Gallie, Brooks, and Magerl were compared
      biomechanically. Sixteen human C1-C2 segments with odontoid fractures of type II
      and III were investigated under standardized conditions. Flexion and extension
      moments, anterior, and posterior shear forces, left and right torsional moments
      were applied, and the motion of C1 relative to C2 was determined. The results of
      this investigation show clearly that the segments treated with the technique by
      Magerl with transarticular screws achieved the highest stiffness, compared to the
      wiring methods of Brooks and Gallie. These differences were most evident for
      posterior shear forces and for torsional moments. For these load conditions the
      ratio of stiffness Magerl:Brooks:Gallie was about 10:2:1. Significant differences
      for the plastic deformation of the differently fixed C1-C2 segments were found
      within the first few load/unload cycles, which give information about the
      relationship between primary and long-term stability.

PMID- 20054938
TI  - Traumatic spondylolisthesis of the axis associated with a spinal cord rupture in
      T1.
AB  - Traumatic spondylolisthesis of the axis is rarely associated with neurological
      deficit. The authors describe a case of complete tetraplegia due to spinal cord
      rupture at T1 without any other osteoligamentous lesion at the level. The
      mechanism of this lesion is discussed; it seems to be due to hyperflexion, with
      preceding hyperextension responsible for the C2 pedicular fracture.

PMID- 20054939
TI  - Simultaneous combined anterior and posterior fusion. A review of its concept and
      10 years of refinement of the technique: a solution for the patient with severe
      back and leg pain.
AB  - This paper reviews the principles, developments and concepts embodied in the
      experience gained over 10 years with simultaneous combined anterior and posterior
      fusion (SCAPF) of the spine in over 750 patients. The procedure was initially
      designed for the surgical treatment of failed post-discectomy syndromes.
      Indications have expanded due to increasing experience and the rapid, predictable
      fusion which accompanies this technique. The current technique allows for a solid
      anterior fusion combined with extensive posterior decompression and removal of
      the primary anatomical pain sources involved with low back pain and disability.

PMID- 20054940
TI  - Acceleration injury of the cervical spine by hypertranslation of the head. Part
      I. Effect of normal translation of the head on cervical spine motion: a
      radiological study.
AB  - This paper starts from the concept that acceleration injury of the cervical spine
      is caused by hypertranslation of the head with respect to the trunk, and not by
      hyperflexion or hyperextension. This first part of the paper studies the effect
      of normal head translation upon cervical spine posture and motion. Lateral
      radiographs of the neck in chin-out and chin-in positions reveal that this
      translation produces maximal motion at the cranio-vertebral junction C0-2, from
      full extension in chin-out position to full flexion in chin-in position. Motion
      decreases from C2-3 downward. Below C6 the direction of motion is reversed. The
      normal range of head translation is small, notably with a fixed thoracic spine.
      The hypothesis is developed that hypertranslation of the head will almost
      immediately result in damaging hyperflexion or hyperextension of the
      craniovertebral junction.

PMID- 20054941
TI  - Acceleration injury of the cervical spine by hypertranslation of the head. Part
      II. Effect of hypertranslation of the head on cervical spine motion: discussion
      of literature data.
AB  - This paper starts from the concept that acceleration injury of the cervical spine
      is caused by hypertranslation of the head with respect to the trunk, and not by
      hyperflexion or hyperextension. In this second part of the paper literature
      describing craniovertebral junction damage after acceleration injury is reviewed.
      (All other types of lesions are left out of consideration.) Fatal craniocervical
      disruption has been reported in high-energy acceleration experiments in rhesus
      monkeys. Comparable craniovertebral disruptions occurred in a large proportion of
      cervical spine injuries caused by fatal traffic accidents and in some patients
      surviving such accidents. At least part of these dislocations were inflicted by
      acceleration injury. Taking hypertranslation of the head as the starting point,
      reconstruction of the mechanism of injury in these craniovertebral disruptions is
      done. The "classical" mechanisms, based on hyperflexion or hyperextension, are
      critically reviewed. It is likely that hypertranslation also plays a role in the
      less severe whiplash injury, but this is not further elaborated.

PMID- 20054942
TI  - Results of lumbar discectomy: a study using 15 different evaluation methods.
AB  - Ninety-two patients who had undergone a primary excision of a lumbar disc were
      evaluated using 15 different criteria that evaluate the surgical outcome 2-15.5
      years (average 8.8 years) following operation. The satisfactory results ranged
      from 62% to 84%. Criteria which relied on the subjective opinion of the patient
      gave the best results, while on the contrary the worst results were those that
      relied on functional criteria, such as return to work, return to previous
      employment, general activity level and need of further treatment. This
      variability in results observed with the same group of patients depends to a
      great extent on the nature of criteria used as well as on the design of those
      criteria. The study concludes that the reported outcomes for lumbar spinal
      surgery are influenced by the selection of the criteria used for the assessment
      of the end results.

PMID- 20054943
TI  - Lumbar disc herniation in teenagers.
AB  - We report 48 patients operated on for lumbar disc herniation in the second decade
      of life (aged 13-20 years) in our Neurosurgical Division. To analyze the clinical
      and diagnostic features and surgical outcome of the disease in teenagers and to
      point out any differences from adults, we made a detailed study of over 900
      juvenile cases and compared them with 11000 adult cases reported in the
      literature. Low-back pain proved to be less frequent among youngsters both as a
      first symptom and at diagnosis, while sensorimotor deficits have the same
      frequency in the two age groups. Herniation occurs more often at L4-L5 and is
      more frequently median among teenagers. The long-term surgical results in
      children and adolescents are better than in adults.

PMID- 20054944
TI  - How many days of bed rest for acute low back pain? Objective assessment of trunk
      function.
AB  - Bed rest is usually considered an efficient treatment for acute low back pain.
      However, the optimal duration of bed rest is still being discussed. The
      recommended periods vary from 2 days to 2 weeks. The duration of optimum length
      is an important topic given the economical and physiological drawbacks of
      prolonged inactivity. The purpose of this work is to measure objectively the
      efficacy of two different durations of bed rest through a dynamometric measure of
      trunk function. Some 51 male patients, students or self-employed, being treated
      for acute low back pain were randomized into two groups. Group I was prescribed a
      bed rest period of 3 days and group II, a period of 7 days. We used a multi-axis
      isoinertial trunk testing dynamometric device (Isostation B200, Isotechnologies,
      USA). Patients were all assessed on day 1 and also on day 5 for group I or on day
      9 for group II. The variables measured in the sagittal plane were isometric
      torques in flexion and extension, unresisted range of motion, average dynamic
      torques and average velocities. Patients were also asked to fill in a visual
      analogue pain scale on both assessment days. The improvement of all performance
      measures were important and highly significant (P < 0.001) in both groups. The
      results of the functional testing and the visual analogue pain scale showed no
      significant differences between the groups. In these relatively young and
      motivated patients, a duration of bed rest of 3 days resulted in the same
      objective functional improvement of trunk function and pain rating as a period of
      7 days. This shorter duration should be considered as preferable, given the same
      objective results but important physiological and economical advantages.

PMID- 20054945
TI  - Lumbar spinal canal morphometry from computed tomography scans: reproducibility,
      results and clinical implications.
AB  - The reproducibility of measurements of the lumbar spine taken from computed
      tomography (CT) scans was assessed. The overall variaton in 53 patients scanned
      on more than one occasion was only 2.8%. Factors which reduced the
      reproducibility were increasing angle of scan from the mid-discal plane,
      measurement of oblique structures and measurement of dimensions with soft-tissue
      boundaries. Measurements from 142 patients are presented and compared with both
      other published series and the results from 17 patients with spinal stenosis.
      Whereas the sagittal diameter of the bony canal and the interpedicular distance
      of the patients with spinal stenosis did not differ from the control group, a new
      measurement described in this paper, the oblique sub-facet distance, demonstrated
      significant differences between the two groups.

PMID- 20054947
TI  - Metastatic spinal tumours: survival after surgery.
AB  - Survival analysis of 70 patients with metastatic extradural tumours of the spine
      is presented. The indication for surgery was rapidly progressive cord compression
      as a initial manifestation of a malignant disease in 28 cases (40%), a
      preoperatively known malignant tumour in 28 patients (40%), relapse of cord
      compression after previous successful radiotherapy in 10 cases (14%), instability
      in 3 patients (4%) and uncontrolled pain in 1 patient. In 53 procedures (76%) the
      level of compression was in the thoracic spine, in 9 procedures in the cervical
      spine (13%) and in 8 procedures in the lumbar spine (11%). All patients had
      developed a neural deficit before surgery. Fourteen patients (20%) were able to
      walk prior to surgery, 47 (67%) were paraparetic, and 9 (13%) were paraplegic.
      Eleven patients died in the first 2 weeks following surgery and out of 59
      patients who survived, 39 patients (66%) were able to walk, 11 were paraparetic
      (19%), and 9 were still paraplegic (15%). Bowel and bladder dysfunction was
      present in 37 cases (53%) before surgery and in 16 cases (27%) after surgery.
      Normal sphincter control was regained after 43 (73%) procedures. Persistent back
      pain was present in 60 patients (86%) before surgery and in 13 patients (22%)
      after surgery. The mean survival time for all 70 patients was 45.6 weeks. There
      were 11 early deaths (16%), another 51 patients died from disseminated disease
      (88%), and 8 patients are still alive (11%) with a mean survival of 133 weeks. A
      statistically significantly shorter survival was found in patients with lung
      metastases when compared with the survival of patients with breast metastases and
      the overall survival of patients with other metastatic tumours.

PMID- 20054946
TI  - Selective changes in multifidus dimensions in patients with chronic low back
      pain.
AB  - This study of 52 patients (27 men) with recent (< 18 months) or chronic (> 18
      months) low back and unilateral radicular pain symptoms was undertaken to
      investigate whether wasting of the paraspinal muscle components is generalised or
      selective. During the patients' routine computed tomographic lumbar spinal scans
      a standardised transaxial view was obtained along the upper end-plate of the L4
      vertebra, and the cross-sectional areas of the paraspinal muscles and their
      components, multifidus and erector spinae, estimated. Irrespective of whether the
      symptoms were recent or chronic, multifidus dimensions were significantly greater
      on the side ipsilateral to the radicular pain symptoms. The results indicate
      selective changes of multifidus in these patients and possibly reflect an
      adaptive response by this muscle, such as to an increased role in stabilising the
      lumbar spine in the face of overall paraspinal muscle atrophy.

PMID- 20054948
TI  - Development of spondylolisthesis after growth arrest.
AB  - Based on the observation of three clinical cases of late onset (after growth
      arrest) spondylolisthesis, the different pathogenetic factors for lumbar
      instability in adulthood are discussed. A causal classification based on
      functional and morphological criteria clearly separates the "genuine" traumatic
      spondylolisthesis from other forms causing instability (with spondylolysis)
      within a lumbar motion segment. The possibility of developing spondylolisthesis
      even after growth arrest is hereby proven. Consequences for appraisal procedures
      are discussed, and an example for possible surgical management is given.

PMID- 20054949
TI  - Eosinophilic granuloma of C5 causing cervical cord compression.
AB  - A 2-year-old girl suffering from eosinophilic granuloma of the body of C5
      presented with subluxation of C5 on C6 and neurological impairment due to
      cervical cord compression. Following a diagnostic percutaneous biopsy, the child
      was managed conservatively with halo traction for 9 weeks and recovered
      successfully.

PMID- 20054950
TI  - Posttraumatic vertebral body necrosis (Kummell-Verneuil disease). Case report of
      a rare orthopaedic disease with histopathological correlation.
AB  - We report the case of a delayed partial posttraumatic vertebral body necrosis
      (PVBN) 1 year after a spinal trauma. Operative treatment became necessary due to
      incipient paraplegia. PVBN, also known as Kummell-Verneuil's disease, can occur
      as a rare but serious complication several months or even years after a spinal
      trauma. Radiologically, it often presents with an intravertebral vacuum
      phenomenon. The underlying reasons for the necrosis as mentioned in the
      literature seem to be an initial microtrauma, metabolic disturbances and
      primarily overlooked compression fractures. Histologically, it resembles a
      pseudarthrosis with only little bony reparation, as in an avascular femoral head
      necrosis.

PMID- 20054951
TI  - Spondylolysis and spondylolytic spondylolisthesis. A review of current concepts
      on pathogenesis, natural history, clinical symptoms, imaging, and therapeutic
      management.
AB  - The purpose of this paper is to review the current concepts on spondylolysis and
      spondylolytic spondylolisthesis. The two are very closely connected, and both
      result from a growth disturbance of the lumbosacral vertebrae, linked to the
      human biped standing position, and depending on genetic and environmental
      factors. Pars defect occurs usually in early childhood. The primum movens of
      lumbosacral deformities in spondylolisthesis is the slippage and its
      biomechanical consequences for the growing vertebrae. Most cases are asymptomatic
      but symptomatic cases can be very disabling. Major clinical symptoms are
      presented here, as are the roentgenographic parameters usually required for the
      assessment. Most cases do not require surgery. However, surgical procedures have
      been widely developed in the last 60 years for the cases resistant to non
      operative treatments. They are presented here in a logical order, from the most
      physiological to the most aggressive. Isthmic repair is reliable but requires
      very strict local conditions. Excision of the loose arch alone should no longer
      be practised especially in young patients. Fusions in situ are widely used,
      especially by the posterior approach, but owing to unfavourable biomechanical
      conditions, a significant amount of pseudarthrosis is reported as well as slip
      progression in young patients. Additional internal fixation is recommended.
      Associated reduction allows placement of the spine in the best mechanical
      conditions for a stable fusion. Several procedures have been reported, involving
      either single or staged approaches. Either anterior and posterior fusion
      associated with reduction seems to give the best results, in spite of some few
      cases of transitory neurological involvement. Resection of the olisthetic
      vertebra associated with reduction and fusion is a therapeutic alternative in
      very severe cases in young people. Elective indications are given at the end of
      the Discussion on the basis of current procedures, according to the type of
      lesion and the category of patient.

PMID- 20054952
TI  - Contrast-enhanced MRI versus myelography and contrast-enhanced CT in
      postdiskectomy problems.
AB  - The differentiation between scar tissue and disk herniation is essential in
      postdiskectomy problems of the lumbar spine, since reoperation on scar tissue
      alone is often unfavourable. Epidural scar is a vascularized tissue, and
      enhancement can be seen after intravenous contrast injection, allowing
      differentiation from avascular disk material. Ten patients who had previously
      undergone surgery for lumbar disk herniation and with recurrent symptoms severe
      enough to warrant repeat surgery were examined by myelography, magnetic resonance
      imaging (MRI), and computed tomography (CT) before reoperation. MRI was performed
      with T1- and T2-weighted sequences in sagittal and axial projections before and
      after intravenous contrast injection. CT scans were obtained before and during
      intravenous contrast infusion. Reoperation revealed scar tissue, alone or
      together with disk, in 9 of 10 patients. Enhancement of scar but not of disk
      material was observed on MRI in 8 cases, but in none on CT. No enhancement of
      disk was seen with either modality. The correct diagnosis was given by MRI in 9
      of 10 patients and by CT in 3 of 10. CT was superior to MRI in only 1 patient,
      who had a bony stenosis. Myelography could not separate disk from scar in any
      case. In conclusion, contrast-enhanced MRI was superior to MRI without contrast,
      CT before and after contrast, as well as myelography in discriminating disk from
      scar tissue.

PMID- 20054953
TI  - Management of the herniated lumbar disc: the outcome after chemonucleolysis,
      surgical disc excision and conservative treatments.
AB  - In the 11-year period from 1978 and 1988, myelography was performed on 624
      patients with suspected herniated lumbar discs. Positive findings, defined as an
      indentation of the contrast-filled dural sac and/or lack of contrast filling of
      the nerve roots, were found in 508 (81.4%) patients. Patients with suspected
      spinal stenosis were excluded from the study. The choice of treatment was
      determined by the preference of the consultant in charge. In all, 146 patients
      were treated by chemonucleolysis, 152 patients underwent surgical excision of the
      disc via laminectomy/fenestration, while 210 patients were listed for further
      treatment (albeit chemonucleolysis or laminectomy) but sustained relief of
      symptoms whilst waiting for admission or refused further intervention and
      consequently continued conservative treatments (such as physiotherapy,
      manipulations under anaesthetic, epidural or local injections). Following a
      repetitive questionnaire and clinical review, 78% of those patients that had
      undergone chemonucleolysis were satisfied with their treatment (i.e. symptoms
      were either 'gone', 'much better' or 'better'). Significantly fewer patients were
      satisfied after surgical disc excision or conservative treatments (71% and 61%,
      respectively; P <0.001). Whereas patients with a short duration of symptoms (less
      than 1 year) achieved the best outcome after chemonucleolysis and laminectomy,
      patients with a prolonged history (greater than 2 years) benefitted most from
      conservative methods. Of those patients in whom symptoms were considered to be
      worse or the same following treatment, 46%, 51% and 42% were still working
      following chemonucleolysis, surgery and conservative treatment, respectively. The
      outcome did not depend upon the size of the disc involved. Although this is a
      retrospective study, it is the first report to compare the outcome following
      chemonucleolysis, surgery and conservative methods in patients with disc prolapse
      confirmed by myelography.

PMID- 20054954
TI  - Biomechanical changes of the lumbar intervertebral disc after automated and
      nonautomated percutaneous discectomy: an in vitro investigation.
AB  - A total of 40 human lumbar motion segments were prepared and tested in an
      electromechanical materials testing machine to investigate the biomechanical
      changes, i.e., intradiscal pressure, radial extension, and height of the
      intervertebral disc, after percutaneous discectomy. In 20 discs (group A) the
      nuclear material was excised using the nonautomated percutaneous lumbar
      discectomy technique (NAPLD). In the other 20 (group B) the material was removed
      with the automated percutaneous lumbar discectomy method (APLD). The results of
      the two groups were analyzed statistically and compared to each other. In the
      NAPLD group the removal of 0.1 g freeze-dried nucleus pulposus material reduced
      the height of the disc an average of 0.32 mm, versus 0.47mm in the APLD group.
      The radial bulge increased in both groups after the removal of 0.1 g freeze-dried
      nucleus pulposus material, on average 0.10 mm versus 0.15 mm. The intradiscal
      pressure also decreased in both groups after the removal of 0.1 g freeze-dried
      nucleus pulposus material, on average 0.94 bar versus 1.88 bar. The differences
      between the biomechanical data of the two groups were statistically significant
      for all three parameters (P < 0.05). Our results show that the mechanism for
      improving radicular pain in patients with herniated disc after treatment with
      percutaneous discectomy is still in question. We postulate that loss of height of
      the disc and, as a consequence, reduction of tension in the affected nerve root,
      plays a major role with regard to this improvement.

PMID- 20054955
TI  - Low risk for vertebral slipping after decompression with facet joint preserving
      technique for lumbar spinal stenosis.
AB  - The incidence and magnitude of vertebral slipping after decompression for central
      lumbar spinal stenosis were determined in a prospective study of 60 consecutive
      patients. Mean patient age was 64 (35-83) years, and 35 patients were men. In all
      cases, laminectomy was performed using a facet joint preserving undercutting
      technique. Plain radiographs were obtained before and 1 year after surgery.
      Vertebral slipping and disc degeneration were measured. Preoperative degenerative
      olisthesis was seen in 19 of the 60 patients. Further slipping had occurred in 6
      of these patients by 1 year postoperatively. Of the remaining 41 patients, only 1
      showed a postoperative slipping. Improvement concerning leg pain was reported by
      45 patients, and there was no difference in patients with or without
      postoperative slipping. It is concluded that decompression with a facet joint
      preserving technique yielded a low risk for postoperative vertebral slipping. The
      risk for slip was higher in patients with preoperative degenerative olisthesis
      but was still less than 1/3. Vertebral slipping did not influence the outcome of
      the operation at 1 year. Our results do not support the routine use of spinal
      fusion in connection with decompression for lumbar spinal stenosis.

PMID- 20054956
TI  - Dysraphic problems in the lumbar spine: dilemmas in management--a review of 49
      cases.
AB  - Occult spinal dysraphism can present in many ways. In this review the clinical
      features, pathology, and management of 49 adult and pediatric cases are
      discussed. Most recent papers agree that surgery should be performed for clinical
      deterioration, and many now advise prophylactic surgery for stable or
      asymptomatic patients. This paper questions the role of prophylactic surgery in
      such patients. The natural history of occult dysraphism is not known,
      particularly in the case of adult or asymptomatic patients A conservative
      management policy, with operation reserved for subsequent clinical or
      electrophysiological deterioration, is still acceptable in stable or asymptomatic
      patients. The prospective study of cohorts of patients, with the various forms of
      occult spinal dysraphism, from units with differing management policies, will
      help to clarify the natural history of this condition and whether this may be
      influenced by prophylactic surgery.

PMID- 20054957
TI  - Biomechanical testing of three newly developed transpedicular multisegmental
      fixation systems.
AB  - A series of 216 biomechanical tests with 36 calf spines were performed to
      evaluate the rigidity of three newly developed prototypes of transpedicular
      fixation systems (Spine Fix, AO/ASIF prototype 1, AO/ASIF prototype 2) as
      compared to the already established Cotrel-Dubousset (CD) system. The Spine Fix
      system follows the same principle of spinal fixation as the CD system, while the
      two prototypes of the AO/ASIF group introduce a new concept of spinal reduction
      and fixation technique, using a three-dimensional adjustable fastening system of
      transpedicular screws to a longitudinal rod. This allows for correction and
      fixation of the instrumented vertebra segments in any position. During the tests
      the main point of interest was whether the newly gained degrees of freedom are
      associated with a loss of stiffness in the construct. Furthermore, the study
      evaluated whether transpedicular systems should be optimized from the
      technological point of view, or whether the stability and rigidity of these
      systems is determined mainly by the quality of pedicular anchorage. Load
      displacement was measured using a calf spine model with a precisely defined three
      column lesion. Each implant was loaded up to 15 Nm in flexion, extension, lateral
      bending, and axial rotation. In all tests, the construct behaved in a highly
      linear fashion (r2> 0.94). By continously measuring the forces and moments at the
      cranial end of the spine specimen high accuracy of the tests was achieved
      (standard deviation: x-axis, 1.74%; y-axis, 1.36%; z-axis, 1.21%). In general,
      the stifness was found to be highest in lateral bending, followed by
      flexion/extension and axial rotation. Spine Fix was the stiffest implant in
      flexion/extension, AO/ASIF prototype 1 in lateral bending, and AO/ ASIF prototype
      2 in rotation. In comparison to the CD system (stiffness of CD = 100%),
      differences in stiffness ranged from 77.3% prototype 1 to 140.8% Spine Fix in
      flexion, from 78.2% prototype 2b to 134.7% Spine Fix in extension, from 108.1%
      prototype 2b to 213.5% prototype 1 in lateral bending, and from 80.3% prototype 1
      to 110.6% prototype 2 in axial rotation. The Spine Fix and prototype 2 systems
      showed equal or higher stiffness coefficients compared to the CD system.
      Prototype 1 is significantly more flexible, except in lateral bending, than the
      CD. From the technical point of view, the two AO/ ASIF prototypes allow the
      correction and fixation of an instrumented vertebra in any position. Prototype 2,
      despite the additional joint between transpedicular screws and longitudinal rods,
      shows stiffness comparable to that of the CD system.

PMID- 20054958
TI  - Results of lumbosacral distraction spondylodesis for the treatment of
      spondylolisthesis, failed-back syndrome, and lumbar instability.
AB  - Various methods of lumbosacral fusions for the treatment of degenerative spinal
      diseases are used clinically. Results vary greatly depending on indication, type
      of fusion, implants, and method of evaluation. In a retrospective clinical and
      radiological examination after an average follow-up time of 3.9 years this study
      reports on the outcome of lumbosacral distraction spondylodesis (LSDS) in a
      consecutive series of 147 patients being fused for the treatment of
      spondylolisthesis, failed-back syndrome, or lumbar instability. LSDS consists of
      a posterolateral fusion together with an autologous corticocancellous H-graft
      wedged under distraction between the spinous processes of L4 and S1. With 81.0%
      good and excellent results this noninstrumented fusion technique showed the best
      outcome in patients with spondylolisthesis, while in cases with a failed-back
      syndrome or lumbar instability only 62.3% excellent to satisfying outcomes were
      noted. The rate of pseudarthrosis was 13.6% in the whole patient group; no major
      complications such as nerve root damage, postoperative neurological deficits, or
      spinal stenosis were found.

PMID- 20054959
TI  - Translaminar facet joint screws to enhance segmental fusion of the lumbar spine.
AB  - From 1984 to 1988, 70 consecutive lumbar and lumbosacral spine fusions enhanced
      with translaminar facet joint screws were performed for segmental degenerative
      disease. Twenty patients had partial decompression of central stenosis, 15
      concomitant discectomy, and 19 lateral nerve root decompression. The mean time to
      fusion was 4.5 months (range 2-7 months). At followup (average 45 months; range
      24-74 months) 98.5% were judged to have solid fusion. Satisfactory results were
      observed in 84% of cases, 91% without previous surgery and 75% after previous
      discectomy. Supplementation of posterolateral fusion by translaminar facet screws
      significantly improved time to fusion, fusion rate, and clinical outcomes with no
      significant increased complications.

PMID- 20054960
TI  - Spinal stabilization for patients with metastatic lesions of the spine using a
      titanium spacer.
AB  - Anterior decompression in spinal metastases of the corporal type with impending
      (n = 5) or present (n = 36) neurological complications was performed in 41
      patients. For reconstruction, a titanium cylinder was inserted after
      spondylectomy and augmented with an anterior plate. The titanium implant can
      easily be adjusted to the length needed without necessitating expensive
      additional equipment. Outside the patient the implant is filled with
      polymethylmetacrylate, facilitating plate transfixation for rotational locking.
      There was a 30-day mortality of 9.7%. Pain relief was apparent in 38 of 41
      patients (92.7%), and motor improvement was manifest in 31 of 35 cases (88.6%).
      Six patients did not present with any neurological symptoms pre- or
      postoperatively. Neurological deterioration was registered in only 1 case (2.4%).
      Surgical efficacy was maintained until the death of the patients. Though tumor
      recurrence at a different spinal level led to consecutive surgery in 5 patients,
      no implant dislocation occurred during the observation period (maximum 44
      months), characterizing the procedure as a mechanically reliable and safe
      technique.

PMID- 20054961
TI  - Monostotic fibrous dysplasia of a cervical vertebra.
AB  - Fibrous dysplasia has been frequently reported to involve the spine in the
      polyostotic form, but only rarely in the monostotic form of the disease. The
      present case demonstrates monostotic fibrous dysplasia of the fourth cervical
      vertebra. We present the plain radiographic, CT-scan, scintigraphy and histologic
      examinations. C3-C4 posterior and anterior arthrodesis was performed. The post
      operative follow-up was satisfactory.

PMID- 20054962
TI  - Can it work? Catholic, secular facilities plan affiliation in N.H.

PMID- 20054963
TI  - When sorry is enough. Study finds owning up to mistakes better approach.

PMID- 20054964
TI  - Mining the data. Feds leaning on technology to target waste, fraud.

PMID- 20054965
TI  - Largest healthcare unions. Ranked by national membership within the healthcare
      industry.

PMID- 20054966
TI  - Still no 'meaning'. Health IT industry still waiting on CMS' use rules.

PMID- 20054967
TI  - Blues' profitable year. 2008 revenue hits $411 million, with profits up 28%;
      Serota earns $4 million.

PMID- 20054969
TI  - Largest professional liability carriers. Ranked by U.S. direct medical
      malpractice premiums written in 2008.

PMID- 20054968
TI  - Workers behaving badly. Survey: problems still exist; to what extent debated.

PMID- 20054970
TI  - Pathogen-derived immunomodulatory molecules. Preface.

PMID- 20054971
TI  - Bacterial toxins as immunomodulators.
AB  - Bacterial toxins are the causative agent at pathology in a variety of diseases.
      Although not always the primary target of these toxins, many have been shown to
      have potent immunomodulatory effects, for example, inducing immune responses to
      co-administered antigens and suppressing activation of immune cells. These
      abilities of bacterial toxins can be harnessed and used in a therapeutic manner,
      such as in vaccination or the treatment of autoimmune diseases. Furthermore, the
      ability of toxins to gain entry to cells can be used in novel bacterial toxin
      based immuno-therapies in order to deliver antigens into MHC Class I processing
      pathways. Whether the immunomodulatory properties of these toxins arose in order
      to enhance bacterial survival within hosts, to aid spread within the population
      or is pure serendipity, it is interesting to think that these same toxins
      potentially hold the key to preventing or treating human disease.

PMID- 20054972
TI  - Innate immune evasion by staphylococci.
AB  - When bacteria invade the human host, they are directly confronted with a serious
      threat, the human innate immune system. This chapter describes the challenge that
      a staphylococci face and recent findings on how this bacterium counteracts the
      massive attack of this innate immune system. In order to survive within the human
      host, staphylococci have evolved a wide variety of small, excreted proteins that
      interfere with subsequent steps of the human innate immune system cascade.

PMID- 20054973
TI  - Bacterial complement escape.
AB  - Complement activation is a crucial step in our innate immune defense against
      invading bacteria. Complement proteins can quickly recognize invading bacteria
      and subsequently label them for phagocytosis or kill them by direct lysis. In
      order to survive in the human host, bacterial pathogens have evolved a number of
      excreted and membrane-bound proteins that interfere with several steps of the
      complement cascade. In this chapter we summarize the most successful complement
      modulating strategies by human bacterial pathogens.

PMID- 20054974
TI  - Modulation of innate immune signalling pathways by viral proteins.
AB  - In recent years an explosion of information on the various strategies viruses
      employ to penetrate and hijack the host cell has led to an increased
      understanding of both viruses themselves and the host immune response. Despite
      their simplicity viruses have evolved a number of strategies to not only evade
      the host immune response but also modulate immune signalling to favour their
      replication and survival within the cell. The innate immune response provides the
      host with an early reaction against viruses. This response relies heavily upon
      the recognition of pathogen-associated molecular patterns (PAMPs) by a number of
      host pattern recognition receptors (PRRs), leading to activation of innate
      signalling pathways and altered gene expression. In this chapter we outline the
      signalling pathways that respond to viral infection and the various methods that
      viruses utilize to evade detection and modulate the innate immune response to
      favour their survival.

PMID- 20054975
TI  - Viral TNF inhibitors as potential therapeutics.
AB  - The immune system functions by maintaining a delicate balance between the
      activities of pro-inflammatory and anti-inflammatory pathways. Unbalanced
      activation of these pathways often leads to the development of serious
      inflammatory diseases. TNF (Tumor Necrosis Factor) is a key pro-inflammatory
      cytokine, which can cause several inflammatory diseases when inappropriately up
      regulated. Inhibition of TNF activities by using modulatory recombinant proteins
      has become a successful therapeutic approach to control TNF activity levels but
      these anti-TNF reagents also have risks and certain limitations. Biological
      molecules with a different mode of action in regulating TNF biology might provide
      a clinically useful alternative to the current therapeutics or in some cases
      might be efficacious in combination with existinganti-TNF therapies. TNF is also
      a powerful host defense cytokine commonly induced in the host response against
      various invading pathogens. Many viral pathogens can block TNF function by
      encoding modulators of TNF, its receptors or downstream signaling pathways. Here,
      we review the known virus-encoded TNF inhibitors and evaluate their potential as
      alternative future anti-TNF therapies.

PMID- 20054976
TI  - Lipoxins as an immune-escape mechanism.
AB  - Here, we discuss the mechanisms of repression of signaling pathways that are
      triggered by Lipoxin (LX) and are responsible for control of pro-inflammatory
      response during chronic phase of Toxoplasma gondii infection. We also discuss
      this mechanism from the perspective of the pathogen, which pirates the host's
      lipoxygenase machinery to its own advantage as a probable immune-escape
      mechanism. Pro-inflammatory mediators such as IL-12, IFN-gamma and TNF are
      essential in controlling parasite growth during T. gondii infection. However, it
      is clear that exacerbated production of these cytokines results in host tissue
      damage. LX, an anti-inflammatory eicosanoid, plays an important role in
      regulation of immune response to T. gondii.

PMID- 20054977
TI  - Immunomodulatory activity and therapeutic potential of the filarial nematode
      secreted product, ES-62.
AB  - ES-62 is a protein that is actively secreted by filarial nematodes during
      parasitism of the vertebrate host. The molecule is able to directly interact with
      a number of cells of the immune system including B-lymphocytes, dendritic cells,
      macrophages and mast cells. Interaction appears to be dependent on complexing
      with TLR4 and results in modulation of the activity of a number of signal
      transduction molecules including MAP kinases, PI-3 kinase and NF-kappaB.
      Immunomodulatory activity of ES-62 appears to be largely due to the presence of
      phosphorylcholine (PC) moieties covalently attached to N-type glycans. The net
      effect of ES-62's interaction with the immune system is the generation of an anti
      inflammatory immunological phenotype. As a consequence of this, ES-62
      demonstrates striking drug-like activity in models of disease associated with
      aberrant inflammation, in particular those associated with autoimmunity and
      allergy.

PMID- 20054978
TI  - Helminth-derived immunomodulatory molecules.
AB  - Infection of man with parasitic helminths leads to potent activation and
      modulation of the host immune response. This modulation of immunity by helminth
      infections may have bystander effects in altering, either suppressing or
      exacerbating, unrelated inflammatory processes. Various ongoing clinical trials
      are testing the therapeutic application of helminth infection of patients with
      inflammatory diseases, including inflammatory bowel disease and allergic
      disorders. Rather than the use of live helminth infection, with the potential for
      side effects, an alternative approach is to identify the immune modulatory
      molecules (IM) produced by helminths that can alter immune functions. In this
      review, we will focus on characterized helminth-derived IMs that may have
      potential to be developed as novel therapeutics for inflammatory diseases.

PMID- 20054979
TI  - Fungal-derived immune modulating molecules.
AB  - Invasive fungal infections are an increasing clinical problem for which new
      therapeutic approaches are needed. Understanding the initial interaction between
      fungi and the host offers potential for development of new drugs or vaccines. It
      has recently been recognized that like other pathogens, fungi initially interact
      with the innate immune system via binding between fungus-specific chemical
      signatures (pattern-associated molecular patterns or PAMPs) and pattern
      recognition receptors (PRRs) on mononuclear phagocytes. Fungal PAMPs are
      restricted to complex carbohydrates in the cell wall, including mannoproteins,
      phospholipomannan, beta-glucans and possibly chitin. These PAMPs bind
      specifically to two classes of PRR in phagocyte membranes, toll-like receptors
      and C-lectin-like receptors, through which they initiate signaling responses that
      culminate in release of pro- and anti-inflammatory cytokines, link the innate
      immune response with the adaptive immune response and initiate phagocytosis and
      intracellular killing. Isolated PAMPs have been used to dissect phagocyte
      responses in vitro and have revealed mechanisms by which host cells can tailor
      innate immune responses to individual pathogens. The interactions are complex and
      are yet to be translated into a clear understanding of the roles of the
      respective PAMPs and PRRs in vivo. Recent advances in this area in relation to
      the pathogenesis of fungal infections are summarized in this chapter.

PMID- 20054980
TI  - The immunosuppresive tick salivary protein, Salp15.
AB  - The interaction between Ixodid ticks and their mammalian hosts is a complex
      relationship. While the mammalian host tries to avoid the completion of the
      feeding process, the tick has devised strategies to counteract these attempts.
      Tick saliva contains a vast array of pharmacological activities that presumably
      aid the tick to evade host responses, including anticomplement, oxidative and
      innate and adaptive immune responses. The characterization of these activities
      has gained momentum in the last several years. One of the best studied activities
      present in tick saliva corresponds to the antigen known as Salp15, which binds
      specifically to the T-cell coreceptor CD4 resulting in the specific repression of
      CD4+ T-cell activation. We discuss here the current state of our knowledge of the
      mode of action of this salivary protein.

PMID- 20054981
TI  - The serpin saga; development of a new class of virus derived anti-inflammatory
      protein immunotherapeutics.
AB  - Serine proteinase inhibitors, also called serpins, are an ancient grouping of
      proteins found in primitive organisms from bacteria, protozoa and horseshoe crabs
      and thus likely present at the time of the dinosaurs, up to all mammals living
      today. The innate or inflammatory immune system is also an ancient metazoan
      regulatory system, providing the first line of defense against infection or
      injury. The innate inflammatory defense response evolved long before acquired,
      antibody dependent immunity. Viruses have developed highly effective stratagems
      that undermine and block a wide variety of host inflammatory and immune
      responses. Some of the most potent of these immune modifying strategies utilize
      serpins that have also been developed over millions of years, including the
      hijacking by some viruses for defense against host immune attacks. Serpins
      represent up to 2-10 percent of circulating plasma proteins, regulating actions
      as wide ranging as thrombosis, inflammation, blood pressure control and even
      hormone transport. Targeting serpin-regulated immune or inflammatory pathways
      makes evolutionary sense for viral defense and many of these virus-derived
      inhibitory proteins have proven to be highly effective, working at very low
      concentrations--even down to the femptomolar to picomolar range. We are studying
      these viral anti-inflammatory proteins as a new class of immunomodulatory
      therapeutic agents derived from their native viral source. One such viral serpin,
      Serp-1 is now in clinical trial (conducted by VIRON Therapeutics, Inc.) for acute
      unstable coronary syndromes (unstable angina and small heart attacks),
      representing a 'first in class' therapeutic study. Several other viral serpins
      are also currently under investigation as anti-inflammatory or anti-immune
      therapeutics. This chapter describes these original studies and the ongoing
      analysis of viral serpins as a new class of virus-derived immunotherapeutic.

PMID- 20054982
TI  - Helminthic therapy: using worms to treat immune-mediated disease.
AB  - There is an epidemic of immune-mediated disease in highly-developed
      industrialized countries. Such diseases, like inflammatory bowel disease,
      multiple sclerosis and asthma increase in prevalence as populations adopt modern
      hygienic practices. These practices prevent exposure to parasitic worms
      (helminths). Epidemiologic studies suggest that people who carry helminths have
      less immune-mediated disease. Mice colonized with helminths are protected from
      disease in models of colitis, encephalitis, Type 1 diabetes and asthma. Clinical
      trials show that exposure to helminths reduce disease activity in patients with
      ulcerative colitis or Crohn's disease. This chapter reviews some of the work
      showing that colonization with helminths alters immune responses, against
      dysregulated inflammation. These helminth-host immune interactions have
      potentially important implications for the treatment of immune-mediated diseases.

PMID- 20054983
TI  - Chemokine binding proteins encoded by pathogens.
AB  - Chemokines are chemoattractant cytokines that play an important role in immunity.
      The role of chemokines against invading pathogens is emphasized by the expression
      of chemokine inhibitors by many pathogens. A mechanims employed by poxviruses and
      herpesviruses is the secretion of chemokine bindingproteins unrelated to host
      receptors that bind chemokines with high affinity and block their activity.
      Soluble chemokine binding proteins have also been identified in the human
      parasite Schistosoma mansoni and in ticks. The binding specificity of these
      inhibitors of cell migration point at chemokines that contribute to host defense
      mechanisms against various pathogens. Chemokine binding proteins modulate the
      immune response and may lead to new therapeutic approaches to treat inflamatory
      diseases.

PMID- 20054985
TI  - Multiclass primal support vector machines for breast density classification.
AB  - Parenchymal patterns defining the density of breast tissue are detected by
      advanced correlation pattern recognition in an integrated Computer-Aided
      Detection (CAD) and diagnosis system. Fractal signatures of density are modelled
      according to four clinical categories. A Support Vector Machine (SVM) in the
      primal formulation solves the multiclass problem using 'One-Versus-All' (OVA) and
      'All-Versus-All' (AVA) decompositions, achieving 85% and 94% accuracy,
      respectively. Fully automated classification of breast density via a texture
      model derived from fractal dimension, dispersion, and lacunarity moves current
      qualitative methods forward to objective quantitative measures, amenable with the
      overarching vision of substantiating the role of density in epidemiological risk
      models of breast cancer.

PMID- 20054986
TI  - Predicting multiple binding modes using a kernel method based on a vector space
      model molecular descriptor.
AB  - We describe the use of our Vector Space Model Molecular Descriptor (VSMMD), based
      on a Vector Space Model (VSM) that is suitable for kernel studies in Quantitative
      Structure-Activity Relationship (QSAR) modelling. Our experiments provide
      convincing comparative empirical evidence that this kernel method can provide
      sufficient discrimination to predict various biological activities of a molecule
      with reasonable accuracy. Furthermore, together with a kernel feature space
      algorithm, experiments also provide convincing empirical evidence that our VSMMD
      can provide sufficient information to identify different binding modes with high
      accuracy.

PMID- 20054984
TI  - Identification of condition-specific regulatory modules through multi-level motif
      and mRNA expression analysis.
AB  - Many computational methods for identification of transcription regulatory modules
      often result in many false positives in practice due to noise sources of binding
      information and gene expression profiling data. In this paper, we propose a multi
      level strategy for condition-specific gene regulatory module identification by
      integrating motif binding information and gene expression data through support
      vector regression and significant analysis. We have demonstrated the feasibility
      of the proposed method on a yeast cell cycle data set. The study on a breast
      cancer microarray data set shows that it can successfully identify the
      significant and reliable regulatory modules associated with breast cancer.

PMID- 20054987
TI  - Simulation of genomic recombination and the influence of DNA sequence diversity
      on cluster formation and detectability of recombination: a scientific workflow
      method.
AB  - The detection of recombination from DNA sequences is relevant to the
      understanding of evolutionary and molecular genetics. We developed a
      Recombination Simulation Scientific Workflow System (RSSWS) for simulating
      recombination and using GENECONV to test the effect of pairwise differences in a
      diverse population on the detectability of recombination. Decreases in
      recombination rate owing to pairwise differences resulted in population clusters
      analogous to sympatric speciation under specific conditions and decreases in
      detectability of recombination, a phenomenon that we call 'cryptic
      recombination'. This computational method demonstrated the value of scientific
      workflow methods for analysing a complex process and data driven problem.

PMID- 20054988
TI  - Data mining pathogen genomes using GeneOrder and CoreGenes and CGUG: gene order,
      synteny and in silico proteomes.
AB  - Sequence databases are growing exponentially due to 'next generation' DNA
      analysers and applications of these data. Databases include multiple sequences of
      previously sequenced organisms, particularly ones of consequence to human health.
      Applications are limited by tools available to mine them, particularly user
      friendly tools that are useful for bench researchers. GeneOrder, CoreGenes and
      CGUG are web-based 'on-the-fly' tools that examine gene order and synteny, as
      well as proteomes for comparative genomics and for drug discovery and design
      targets. CoreGenes (CGUG) now allows analysis of genomes ranging up to 1.9
      megabases. Many of these small genome bacteria have impacts on human health.

PMID- 20054989
TI  - Promoting synergistic research and education in computational biology and drug
      design.
AB  - Supported by US National Science Foundation (NSF) and the International Society
      of Intelligent Biological Medicine (ISIBM), the IEEE 7th International Conference
      on Bioinformatics and Bioengineering at Harvard Medical School was designed
      dynamically in response to the cutting edge synergistic research and education.
      One of the key components of this academic event is the poster presentation
      focusing on specific topics to foster collaboration between the computational
      biology and drug design domains. The Harvard meeting attracted over five hundred
      scientists, researchers and medical doctors world-wide to present, discuss and
      exchange their research. The synergies between computational biology and drug
      design research had been well observed by participants. The poster sessions had
      been designed to be responsive to the need for synergistic
      inter/multidisciplinary research and education. A panel of judges was formed to
      decide the best posters. The papers in this special issue were selected for
      runners-up of the best poster award by a panel of judges. Authors were then
      invited to expand their posters into full research papers. Submitted papers were
      required to contain significant additional scientific detail and were rigorously
      reviewed by at least three external reviewers. Detailed information regarding the
      academic event can be found at the White Paper of the IEEE 7th International
      Conference on Bioinformatics and Bioengineering at Harvard Medical School at BMC
      Genomics http://www.biomedcentral.com/1471-2164/9/S2/I1.

PMID- 20054990
TI  - Consensual classification of drug and nondrug compounds.
AB  - A special consensual approach is discussed for separating a molecular group with
      a proven pharmacological activity from another molecular group without any
      activity. It is mainly a group decision to produce a consensus of multiple
      classification results obtained with a single classification algorithm. For this
      purpose, the constructed model has a preprocessing unit which consists of
      transformation of input patterns by random matrices and median filtering to
      generate independent errors for a single type of classifier and postprocessing
      for consensus. The neural network based consensus classifier operating with MOE
      descriptors was applied to a set of 641 chemical structures. The confirmed drugs
      were classified with an accuracy of 86.54% while nondrugs resulted in 82.67%
      accuracy.

PMID- 20054991
TI  - Towards predicting protein-protein interactions in novel organisms.
AB  - Machine learning methods are often used to predict Protein-Protein Interactions
      (PPI). It is common to develop methods using known PPI from well-characterised
      reference organisms, drawing from that organism data for inferring a predictive
      model and evaluating the model. We present evidence that this practice does not
      give a meaningful indication of the model's performance on genetically distinct
      organisms. We conclude that this practice cannot be applied to proteins inferred
      from the genetic sequence of a novel organism for which no PPI data is available,
      and that there is need for evaluating such methods on organisms distinct from
      their training organisms.

PMID- 20054992
TI  - An integrated probabilistic approach for gene function prediction using multiple
      sources of high-throughput data.
AB  - Characterising gene function is one of the major challenging tasks in the post
      genomic era. Various approaches have been developed to integrate multiple sources
      of high-throughput data to predict gene function. Most of those approaches are
      just used for research purpose and have not been implemented as publicly
      available tools. Even for those implemented applications, almost all of them are
      still web-based 'prediction servers' that have to be managed by specialists. This
      paper introduces a systematic method for integrating various sources of high
      throughput data to predict gene function and analyse our prediction results and
      evaluates its performances based on the competition for mouse gene function
      prediction (MouseFunc). A stand-alone Java-based software package 'GeneFAS' is
      freely available at http://digbio. missouri.eduigenefas.

PMID- 20054993
TI  - An ensemble machine learning approach to predict survival in breast cancer.
AB  - Current breast cancer predictive signatures are not unique. Can we use this fact
      to our advantage to improve prediction? From the machine learning perspective, it
      is well known that combining multiple classifiers can improve classification
      performance. We propose an ensemble machine learning approach which consists of
      choosing feature subsets and learning predictive models from them. We then
      combine models based on certain model fusion criteria and we also introduce a
      tuning parameter to control sensitivity. Our method significantly improves
      classification performance with a particular emphasis on sensitivity which is
      critical to avoid misclassifying poor prognosis patients as good prognosis.

PMID- 20054994
TI  - Molecular modelling insights into DFNA15 mediated enhancement of POU4F3
      stability.
AB  - The POU4F3 transcription factor is expressed in the cochlear and vestibular hair
      cells of the inner ear and its targeted deletion results in a loss of inner ear
      hair cells. The DFNA15 truncation mutation has been demonstrated to result in a
      loss of transcriptional activity, but an increase in the stability of the
      protein. Molecular modelling is utilised to propose a mechanism of stability
      enhancement, via an interaction between the truncated POU(HD) domain and the
      POU(S) domain of the transcription factor.

PMID- 20054995
TI  - Implementing bioinformatic workflows within the bioextract server.
AB  - Computational workflows in bioinformatics are becoming increasingly important in
      the achievement of scientific advances. These workflows typically require the
      integrated use of multiple, distributed data sources and analytic tools. The
      BioExtract Server (http://bioextract.org) is a distributed service designed to
      provide researchers with the web ability to query multiple data sources, save
      results as searchable data sets, and execute analytic tools. As the researcher
      works with the system, their tasks are saved in the background. At any time these
      steps can be saved as a workflow that can then be executed again and/or modified
      later.

PMID- 20054996
TI  - Evaluating DNA sequence searching algorithms on multicore.
AB  - Sequence searching is one of major operations in modern bioengineering. Recent
      emerging multicore provides a promising technology to enhance sequence searching
      performance. However, efficiently employing the multicore for a uniprocessor
      oriented algorithm is a difficult task. This paper presents a methodology to
      profile processing requirements for DNA sequence search algorithms, parallelise
      them onto multicore, and analytically evaluate their performance. The key feature
      of this methodology is that entire processes are automated and it requires users
      little understanding of the complexity of algorithms and multicore hardware
      architecture. Our methodology considers three approaches to parallelise searching
      operations: queries, database, and task segmentation.

PMID- 20054997
TI  - Improving prediction accuracy of drug activities by utilising unlabelled
      instances with feature selection.
AB  - Molecular activities can be predicted by Quantitative Structure Activity
      Relationship (QSAR). Because of the high cost of experiments, the number of drug
      molecules with known activity is much less than that of unknown, to predict
      molecular activities utilising unlabelled instances will be an interesting issue.
      Here, Semi-Supervised Learning (SSL) is introduced and a SSL method, Co-Training
      is investigated on predicting drug activities utilising unlabelled instances. At
      the same time, a novel algorithm called FESCOT is proposed, which applies feature
      selection to remove redundant and irrelevant features for Co-Training. Numerical
      experimental results show that Co-Training and feature selection helps to improve
      the prediction ability of Co-Training.

PMID- 20054998
TI  - Prediction of lipid-interacting amino acid residues from sequence features.
AB  - Proteins and lipids are integral components of cell membranes, and play important
      roles in cell signalling. Alterations of normal protein-lipid recognition may
      cause various diseases. However, molecular mechanisms underlying protein-lipid
      recognition are still poorly understood. In this study, we have developed a
      support vector machine-based approach for predicting lipid-interacting residues
      from amino acid sequence features. To the best of our knowledge, this is the
      first study that applies machine learning to sequence-based prediction of lipid
      interacting residues in proteins. Our study provides useful information for
      understanding protein-lipid interactions, and may lead to advances in drug
      discovery.

PMID- 20054999
TI  - A comparison of algorithms for a complete backtranslation of oligopeptides.
AB  - In the context of new metabolic pathways discovery, a full backtranslation of
      oligopeptides can be a promising approach. When studying complex environments
      where the composing microorganisms are unknown it is also preferable to have all
      the complete nucleic sequences corresponding to an enzyme of interest. In this
      paper, we revisit the existing bioinformatics applications, which bring partial
      reverse translation solutions, and we compare two algorithms based on
      oligopeptide degeneracy able to efficiently compute a complete backtranslation of
      oligopeptides. Such algorithms are precious for the discovery of new organisms
      and we show their performances on simulated and real biological data sets.

PMID- 20055000
TI  - Detection and prediction of alternative splicing in Arabidopsis thaliana.
AB  - Alternative splicing is an important process for increasing the diversity arising
      from a single gene. Presently, most studies aimed at detecting alternatively
      spliced genes use Expressed Sequence Tags (ESTs). However, the EST studies based
      on spliced transcripts analyse sequences by alignment rather than sequence
      patterns. Second, EST libraries can be of uncertain quality. To address these
      issues and to improve the quality of detection and prediction for alternative
      splicing, we propose a method that primarily uses pre-mRNAs. It is achieved by a
      decision tree algorithm using triplet nucleotides as attributes for each
      chromosome in Arabidopsis thaliana. In addition, we propose a novel algorithm for
      accurate prediction.

PMID- 20055001
TI  - Inferring transcription factor interactions using a novel HV-SVM classifier.
AB  - Interactions between Transcription Factors (TFs) are necessary for deciphering
      the complex mechanisms of transcription regulation in eukaryotes. We proposed a
      novel HV-kernel based SVM classifier to classify TF-TF pairs based on their
      protein domains and GO annotations. Two types of pairwise kernels, namely, a
      horizontal kernel and a vertical kernel, were combined to evaluate the similarity
      between a pair of TFs, and a Genetic Algorithm was used to obtain kernel and
      feature weights to optimise the classifier's performance. We showed that our
      proposed HV-SVM method can make accurate predictions of TF-TF interactions even
      in the higher and more complex eukaryotes.

PMID- 20055002
TI  - Parsimony accelerated maximum likelihood searches.
AB  - Phylogenetic search is a key tool used in a variety of biological research
      endeavours. However, this search problem is known to be computationally
      difficult, due to the astronomically large search space, making the use of
      heuristic methods necessary. The performance of heuristic methods for finding
      Maximum Likelihood (ML) trees can be improved by using parsimony as an initial
      estimator for ML. The time spent in performing the parsimony search to boost
      performance is insignificant compared to the time spent in the ML search, leading
      to an overall gain in search time. These parsimony boosted ML searches lead to
      topologies with scores statistically similar to the unboosted searches, but in
      less time.

PMID- 20055003
TI  - Approximate strip exchanging.
AB  - Genome rearrangements have been modelled by a variety of primitives such as
      reversals, transpositions, block moves and block interchanges. We consider such a
      genome rearrangement primitive Strip Exchanges. Given a permutation, the
      challenge is to sort it by using minimum number of strip exchanges. A strip
      exchanging move interchanges the positions of two chosen strips so that they
      merge with other strips. The strip exchange problem is to sort a permutation
      using minimum number of strip exchanges. We present here the first non-trivial 2
      approximation algorithm to this problem. We also observe that sorting by strip
      exchanges is fixed-parameter-tractable. Lastly we discuss the application of
      strip exchanges in a different area Optical Character Recognition (OCR) with an
      example.

PMID- 20055004
TI  - Acute and subacute toxicity studies of chitosan reduced gold nanoparticles: a
      novel carrier for therapeutic agents.
AB  - The objective of the present study was to evaluate the oral toxicity of chitosan
      reduced gold nanoparticles so as to demonstrate its applicability for drug
      delivery application. Acute oral toxicity studies in female rats documented no
      deaths or treatment related complications. The LD50 value of gold nanoparticles
      was found to be greater than 2000 mg/kg. In case of sub-acute oral toxicity
      studies, gold nanoparticles were administered orally to male and female rats for
      a period of 28-days. At the end of study blood samples were collected for
      haematology and biochemical analysis. For histopathological analysis, organs of
      animals were weighed and processed for examination. All animals survived the
      duration of the study, with no significant changes in clinical signs, body
      weight, food consumption, hematological parameters, organ weights and
      histopathological findings. These studies establish that chitosan reduced gold
      nanoparticles produced no treatment related toxicity in rats following oral
      administration, thus can be exploited for potential therapeutic applications.

PMID- 20055005
TI  - Semisolid formulation containing a nanoencapsulated sunscreen: effectiveness, in
      vitro photostability and immune response.
AB  - The objective of this work was to verify if hydrophilic gels containing
      benzophenone-3 loaded nanocapsules (HG-NCBZ3) could improve the sunscreen in
      vitro effectiveness against UVA radiation and its photostability compared to a
      conventional hydrogel containing the free sunscreen (HG-BZ3). In parallel, the
      immune response of the nanostructured system was evaluated by mouse ear swelling
      test and the local lymph node assay. The nanocapsules were prepared by
      interfacial deposition of poly(epsilon-caprolactone) and characterized in terms
      of particle size, polydispersity index, zeta potential, drug content and
      encapsulation efficiency. HG-NCBZ3 UV scans showed higher absorption intensity
      values than HG-NCplacebo, prepared using unloaded nanocapsules. Films of the gels
      were irradiated with UVA light and the BZ3 recovery was evaluated by HPLC. BZ3
      recovery decreased from 100% to 29% for HG-BZ3 and to 56% for HG-NCBZ3 after 13
      h. After wavelength scans within 13 h, the relative areas under the curves (AUC)
      decreased from 1.00 to 0.62 for HG-BZ3 and remained constant for HG-NCBZ3.
      Sensitization assay showed that stimulation indexes lower than 3 for all the
      hydrogel samples. Formulations did not induce increases higher than 10% in ear
      swelling, indicating that the hydrogels did not cause cutaneous sensitization in
      mice. The nanoencapsulation improved both the photostability and the
      effectiveness of BZ3 compared to the non-encapsulated sunscreen and the topical
      application of free and nanoencapsulated BZ3 did not produce significant allergy
      response in mice.

PMID- 20055006
TI  - Intra/extracellular biosynthesis of silver nanoparticles by an autochthonous
      strain of Proteus mirabilis isolated from photographic waste.
AB  - There is an enormous interest in developing green synthesis procedures for
      production of nanoparticles by using biomimetic approaches. In our research focus
      has been given to the development of an efficient and eco-friendly viable process
      for the synthesis of nanoscale silver particles using Proteus mirabilis PTCC
      1710, a bacterial strain that was isolated during a screening program from
      photographic waste. A significant result of this study is our observation that
      silver nanoparticles could be induced to synthesis intra and extracellulary. The
      silver nanoparticles were characterized by means of UV-Vis spectroscopy,
      transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS) and
      atomic absorption spectrometer (AAS). The nanoparticles exhibited maximum
      absorbance at 400-410 nm in UV-Vis spectroscopy. TEM images showed formation of
      stable silver nanoparticles of spherical shape with most of the particles in the
      size range of 10-20 nm. It was found that incubation of bacterial cells in Muller
      Hinton broth medium resulted in higher extracellular synthesis of silver
      nanoparticles, whereas intracellular synthesis of silver nanoparticles
      effectively increased in tryptic soy broth. The method of extraction of
      intracellular silver nanoparticles was inexpensive, simple and effective in large
      scale with no need to complex instruments. The bacteria work as a bionanofactory
      which continued to grow after synthesis of silver nanoparticles. The silver
      reduction by this strain is occurred through energy-dependent processes that lead
      to the high output of this reaction. Hence this new approach of using a non
      pathogenic bacterial strain for the successful synthesis of nanosized silvers
      could be easily scaled up which establishes its commercial viability.

PMID- 20055007
TI  - Nanoencapsulation as a way to control the release and to increase the
      photostability of clobetasol propionate: influence of the nanostructured system.
AB  - The aim of this study was to prepare and to evaluate the physicochemical and in
      vitro drug release characteristics of different nanostructured systems containing
      clobetasol propionate (CP): CP-loaded polymeric nanoparticles (nanocapsules and
      nanospheres) and CP-loaded nanoemulsion. Physicochemical characteristics of the
      formulations were monitored up to 9 months after preparation by means of drug
      content, encapsulation efficiency, mean size, polydispersity index, pH, and zeta
      potential. In vitro drug release studies were carried out using the dialysis bag
      method. Photostability of CP-loaded nanoparticles was evaluated by their
      exposition to UVA radiation. All formulations presented nanometric mean size (140
      220 nm), polydispersity index below 0.25, neutral pH values, negative zeta
      potential and encapsulation efficiency close to 100%. All these parameters,
      except pH, remained unchangeable up to 9 months of storage at room temperature
      for CP-loaded nanocapsules. On the other hand, CP-loaded nanospheres and
      nanoemulsion showed an increase in their mean size, as well as in polydispersity
      index under storage (after 3 and 6 months, respectively). In vitro drug release
      studies showed a controlled release of CP from nanoparticles (nanocapsules >
      nanospheres > nanoemulsion) with a low burst release. Photostability of CP under
      UVA radiation was improved by its incorporation into nanoparticles (nanocapsules
      > nanoemulsions > nanospheres).

PMID- 20055008
TI  - Efficient tumor targeting by polysaccharide decked polyethylenimine based
      nanocomposites.
AB  - Hyaluronic acid (HA)-polyethylenimine (PEI, 25 kDa) (HP) nanocomposites were
      fabricated for efficient targeting to solid tumors. Branched PEI was ionically
      blended with a natural mucopolysaccharide, HA, to partially block the positive
      charge and to impart site specificity to HP nanocomposites. A series of
      nanocomposites were prepared by varying the content of HA. HP nanocomposites were
      characterized by their size, morphology, zeta potential and evaluated for pDNA
      protection study, transfection efficiency and cytotoxicity. The competency of HP
      nanocomposites to relocate a plasmid encoding enhanced green fluorescent protein
      (pEGFP) gene was assessed in HEK293, HEK293T, and HeLa cells and found to be
      approximately 1-8 folds efficient compared to Superfect, Fugene, GenePORTER 2. HP
      nanocomposites also exhibited efficient transfection in serum-containing medium.
      MTT assay showed significantly improved cell viability in HEK293T, HepG2 and HeLa
      cells. The specificity of HP nanocomposites to target tumor was investigated in
      vivo by injecting pDNA-loaded HP-4 nanocomposite or PEI intravenously into mice
      bearing Ehrlich ascites tumor (EAT). The gamma scintigraphic studies showed a
      higher accumulation of HP-4 nanocomposite in the solid tumor compared to PEI. The
      results cumulatively advocate that HP nanocomposites could epitomize a viable
      alternative for site specific gene therapy.

PMID- 20055009
TI  - In-vivo imaging of the uptake of upconversion nanoparticles by plant roots.
AB  - Watering of Phalaenopsis and Arabidopsis plants with an aqueous colloidal
      solution of NaYF4:Yb,Er nanoparticles leads to uptake and transport of
      nanoparticles into the plants within a few days. Characteristic upconversion
      emission of the particles can be excited in the shoot and the leaves of the
      plants. Uptake of particles by the root was studied by confocal laser-scanning
      microscopy using excitation in the near-infrared. We demonstrated that
      nanoparticles are able to enter the stele of the plant root and thus the long
      distance transport system despite their relatively large size in comparison to
      the size of the structures responsible for the transport.

PMID- 20055010
TI  - Accumulation of iron oxide nanoparticles by cultured brain astrocytes.
AB  - Magnetic iron oxide nanoparticles are considered for various diagnostic and
      therapeutic applications in brain including their use as contrast agent for
      magnetic resonance imaging or as tool for magnetic drug delivery. However, little
      is known so far on the consequences of a treatment of brain cells with such
      nanoparticles. In order to study the biocompatibility of iron oxide nanoparticles
      and the accumulation of iron from such particles in brain cells, we have used
      astrocyte-rich primary cultures as model system. Iron oxide nanoparticles were
      chemically synthesized with a yield of about 80% regarding the iron content.
      Transmission electron microscopy revealed that the synthesized iron oxide
      nanoparticles had a diameter of about 10 nm. Exposure of astrocyte cultures to
      100 microM iron that were supplied as citrate-coated iron oxide nanoparticles did
      not cause any acute loss in cell viability but resulted in an almost linear
      increase in the cellular iron content that reached after 6 h of incubation at 37
      degrees C a total cellular iron content of about 300 nmol/mg protein. The rate of
      iron accumulation from iron oxide nanoparticles was significantly higher than
      that from the low molecular weight iron complex ferric ammonium citrate (FAC).
      Lowering the incubation temperature from 37 degrees C to 4 degrees C reduced the
      iron accumulation rate from iron oxide nanoparticles or FAC by about 60%. In
      addition, presence of ferric or ferrous iron chelators did not affect the
      cellular iron accumulation from iron oxide nanoparticles. These data suggest that
      cultured astrocytes are able to accumulate intact iron oxide nanoparticles.

PMID- 20055011
TI  - Nanoparticles to increase adhesive properties of biologically secreted materials
      for surface affixing.
AB  - Surface adhesion in nature has been the focus of intense study over the past few
      years. Nevertheless, research in this field has primarily concentrated on
      understanding the chemical aspects of adhesion. While scientists have been able
      to determine some of the molecular structures present in the adhesives secreted
      by surface climbing or surface affixing biological systems such as mussels and
      barnacles, the fundamental adhesion mechanisms used by these systems are still
      unknown. This research paper focuses on the nano-scale morphological similarities
      of adhesive materials secreted from marine mussels, barnacles and ivy. We
      discovered that marine mussels secrete large amounts of adhesive materials in the
      form of nanoparticles for surface adhesion. This is in keeping with our previous
      work, which indicated a similar phenomenon for ivy. Both studies concur with
      earlier research on marine barnacles, polychaetes and sea stars. Taken together,
      these results indicate that nanoparticles are used by natural, biological systems
      to increase surface adhesion. These nanoparticle surface adhesion mechanisms have
      important implications in terms of engineering surface adhesive materials and
      devices.

PMID- 20055012
TI  - Study of the micro- and nanostructured silicon for biosensing and medical
      applications.
AB  - Emerging applications of porous silicon (PS) lies in its ability to incorporate
      other materials, such as organic groups, organic and inorganic nanoparticles to
      form (bio)hybrid systems where each individual constituent may be optimized for a
      particular function. This paper presents our recent experimental results on the
      fabrication and applications in biosensing of the porous silicon (PS) based
      microstructures. We have demonstrated that different morphologies of PS, either
      as-prepared or coated with gold nanoparticles have an important role in
      biomolecule detection, due to its large internal surface combined with specific
      electro-optical properties, being in the same time support for immobilization of
      complementary biomolecules as well as transducer for biochemical interactions.
      Therefore, we have investigated the photoluminescence properties of nanoporous Si
      prepared on different Si micropatterned surfaces comparatively with PS/flat Si in
      order to develop a new simple and versatile process for biosensor transducer
      fabrication. Meso- and macro-PS have been investigated for protein immobilization
      and detection using microarray technique or for DNA biomolecule detection by
      impedance spectroscopy. Finally, we have demonstrated that macroporous silicon
      constitutes an appropriate substrate for very sensitive SERS biosensors. RAMAN
      signal of 11-mercaptoundecanoic acid was investigated on Au/macroporous silicon.
      Various characterisation techniques have been used, optical and scanning electron
      microscopy (SEM) to investigate samples morphology, X-ray diffraction for
      nanoparticle structure, Raman and PL spectroscopy, and laser fluorescence
      detection for chemical and optical properties analysis and impedance spectroscopy
      for investigation organic molecule attachment on the Au/PS structures.

PMID- 20055013
TI  - Novel thermosensitive nano-micelles from triblock copolymer for drug delivery.
AB  - Novel thermosensitive nano-micelles, based on Poly(D,L-lactide-co-glycolide)-b
      poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA), as
      carriers for drug delivery were researched. The critical micelle concentration of
      the copolymer in aqueous solution was determined to be 2.34 microgram/ml by
      fluorescence spectroscopy using pyrene as a fluorescence probe. The lower
      critical solution temperature (LCST) of the copolymer was measured in distilled
      water by optical transmittance, and the LCST was varied from 35 to 55 degrees C
      depending on polymer concentration. Acetaminophen as a model drug was loaded in
      nano-micelles by solvent evaporation method. In vitro acetaminophen release from
      micelles showed a sustained modality compared with the free drug as a control,
      and an obviously high release rate when temperature was increased above LCST. The
      studies showed that nano-micelles made from PLGA-PEG-PLGA could be ideal
      candidate carriers for tumor-special drug delivery.

PMID- 20055014
TI  - Saying no to samples.

PMID- 20055015
TI  - Holding steady.

PMID- 20055016
TI  - HIPAA reaches deeper into practices and beyond.

PMID- 20055017
TI  - Tech-cessorize your practice.

PMID- 20055018
TI  - Clinical Centers of Excellence: Dementia.

PMID- 20055019
TI  - Clinical Centers of Excellence: Dementia. UCLA Mary S. Easton Center for
      Alzheimer's Disease Research. Los Angeles, California.

PMID- 20055020
TI  - Clinical Centers of Excellence: Dementia. Johns Hopkins University School of
      Medicine. Baltimore Maryland.

PMID- 20055022
TI  - A death in the family.

PMID- 20055021
TI  - Clinical Centers of Excellence: Dementia. Neurological Institute of New York. New
      York, New York.

PMID- 20055023
TI  - Medical tourism liability may fall on domestic doctors.

PMID- 20055024
TI  - [Rules, rules and again more rules].

PMID- 20055025
TI  - Ethanol poisoning as a differential diagnosis in a hunter's dog with tetraplegia.
AB  - A 4.5-month-old German pointer was presented with tetraplegia. Based on the
      physical examination, a tentative diagnosis of idiopathic polyneuropathy or
      synaptic disorder was made. Later that day additional information from the owner
      revealed that the dog might have ingested sloe berries that had been used to make
      sloe gin. Ethanol poisoning was added to the differential diagnosis. The dog's
      locomotion recovered in the course of 24 hours. Faecal analysis revealed that the
      animal had ingested at least 127 gin-saturated sloe berries and it was estimated
      that the blood ethanol concentration would have been at least 0.75 per thousand.
      The aetiology, diagnosis, and treatment of ethanol poisoning in dogs is reviewed.

PMID- 20055026
TI  - [A worm infection in the skin of a dog. First autochthonous Dirofilaria repens
      infection ofa dog in the Netherlands].
AB  - The history of an 18-month-old English bulldog with a painful lump in the skin on
      its thigh is described. After opening the nodule a few Dirofilaria repens
      nematodes were found. Oval-shaped transparent eggs with moving larvae were seen
      microscopically. The dog was treated with milbemycin and made a complete
      recovery. The dog had never been abroad, but 6 months earlier in early May had
      been on a campsite in the middle of the Netherlands where many mosquitoes were
      present. This is the first described case of an autochthonous D. repens infection
      of a dog in the Netherlands.

PMID- 20055027
TI  - [Rimadyl lethal?].

PMID- 20055028
TI  - [Education reform in Barneveld, the Netherlands].

PMID- 20055029
TI  - [The Dutch satisfied with the veterinarian].

PMID- 20055030
TI  - [Health and safety law contributes to lower workers' disability].

PMID- 20055031
TI  - [Rude actions from the farmer and veterinarian; the philosophy behind the new
      setup].

PMID- 20055032
TI  - [World congress veterinary parasitology].

PMID- 20055033
TI  - [Hall mark for domestic animal breeding necessary].

PMID- 20055034
TI  - [Symposium tuberculosis].

PMID- 20055035
TI  - [Day of the veterinarian on October 24th a big success].

PMID- 20055036
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, etc. Mantel, cap and the baton of the Veterinary
      University].

PMID- 20055037
TI  - "Just do it"?

PMID- 20055038
TI  - Case acceptance: no random acts allowed.
AB  - Consider implementing a case acceptance system in your office to fully utilize
      your hard-earned clinical skills, and to experience the professional rewards that
      come with serving more patients at a higher level. Doctors who are willing to
      commit the time and resources necessary to improving case acceptance will
      increase the number of implant cases entering the treatment phase--cases that run
      the gamut of complexity and support fees commensurate with their skills!

PMID- 20055039
TI  - Thrombocytopenia and avoiding bleeding complications.

PMID- 20055040
TI  - Upgradeable dentistry, part 4.

PMID- 20055041
TI  - Removing the mystery: treating multirooted teeth.

PMID- 20055042
TI  - Introducing cutting-edge services to your patients.

PMID- 20055043
TI  - A simplified all-ceramic system for complex cases.

PMID- 20055044
TI  - Whitening challenges: tetracycline staining and fluorosis.

PMID- 20055045
TI  - Enhancing technical skills with magnification and illumination.

PMID- 20055046
TI  - LANAP in the general practice: a case report.

PMID- 20055047
TI  - Telescopic bridges: an old technique revisited.

PMID- 20055048
TI  - A six-month orthodontic solution to space closure and bite collapse.

PMID- 20055049
TI  - No support? An easy bite technique.

PMID- 20055050
TI  - An initiative to improve deployment health surveillance.

PMID- 20055051
TI  - Re: Reference data from the automated neuropsychological assessment metrics for
      use in traumatic brain injury in an active duty military sample.

PMID- 20055052
TI  - Re: Methicillin-resistant Staphylococcus aureus infections in U.S. service
      members deployed to Iraq, Military Medicine; April 2009, Vol. 174, 4:408-411.

PMID- 20055053
TI  - National Health Interview Survey on the United States smokers.

PMID- 20055054
TI  - The practice of torturing detainees in Guantanamo Bay.

PMID- 20055055
TI  - Re: Preaccession fitness and body composition as predictors of attrition in U.S.
      Army recruits.

PMID- 20055056
TI  - Mandatory serum TSH screening for all females prior to deployment.

PMID- 20055057
TI  - Treatment of arterial gas embolism.

PMID- 20055058
TI  - Re: Tobacco promotion to military personnel: 'the plums are here to be plucked'.

PMID- 20055059
TI  - A pilgrimage.

PMID- 20055060
TI  - Reserve component troops in the Global War on Terrorism: an increasing debt owed
      the "citizen soldier".

PMID- 20055061
TI  - Health care diplomacy: the Iraq experience and how it can shape the future.

PMID- 20055062
TI  - Telemental health for our soldiers: a brief review and a new pilot program.
AB  - This small but significant telemental health clinical pilot could easily serve as
      a "best practice" model for resource utilization between the nation's VHA/DOD
      institutions that wish to form partnerships and capitalize on resources. It
      demonstrates several potential areas of collaboration for TMH projects. For
      example, this study also points out requisite preparation needs, e.g., an
      information technology (IT) needs assessment, and gap analysis between
      neighboring VHA/DOD installations should be considered beforehand. This would
      address equipment compatibility and address protected health information privacy
      concerns. This preparation would also lead to savings by avoiding equipment
      redundancy and minimize infrastructure (space) investment. While in this instance
      the equipment proved compatible, that may not always be the case. Second,
      regional strategic mapping of staff and services between institutions could help
      in specialty service utilization. This would improve recourse allocation, trim
      numerous costs, and avoid service duplication. A third area of collaboration
      would be the creation of a DOD/VHA electronic credentialing packet. This would
      simplify the preparation phase for TMH delivery and expand the availability of
      scarce medical specialty consultants for both the VHA and DOD. This would serve
      to streamline medical care and expedite the deployment of "virtual" practitioners
      in the event of a national disaster or emergency. To date there have not been any
      technical difficulties at either site and PC-PTSD-positive soldiers continue to
      be evaluated at the SVMAC. Anecdotal reports from both clinicians and patients
      are that they are highly satisfied with TMH delivery services.

PMID- 20055063
TI  - Equity in Veterans Affairs disability claims adjudication in a national sample of
      veterans.
AB  - OBJECTIVES: To address potential equity concerns about the U.S. Department of
      Veterans Affairs' (VA) process for adjudicating military service-related
      disability claims. METHODS: Participants were a nationally representative sample
      of 20,048 veterans completing the 2001 National Survey of Veterans.
      Sociodemographic, access, and illness correlates of both the award and rate of
      general disability benefits awarded by the VA were examined using an established
      theoretical framework. RESULTS: Sociodemographic, access, and illness variables
      were associated with both the award ("yes/no") and rate of benefits (0-100%)
      awarded, with combat exposure, unemployment, and physical impairment accounting
      for the strongest model effects. CONCLUSIONS: Veterans' needs were not
      overshadowed by factors related to demographic background or access (e.g., race,
      gender, insurance), reducing concerns about disparities in general VA disability
      disbursements. These data are timely as disability claims/payments will likely
      increase dramatically in the near future because of current conflicts in the
      Middle East.

PMID- 20055064
TI  - Application of a new resource-constrained triage method to military-age victims.
AB  - OBJECTIVE: Evaluate the resource-constrained, evidence-based, and outcome-driven
      Sacco Triage method (STM) for military-age victims of blunt, penetrating, and
      blast overpressure-like trauma. METHODS: STM is based on a mathematical model of
      resource-constrained triage. Its objective is to maximize expected survivors
      given constraints on transport and treatment resources. STM uses estimates of
      time-dependent victim survival probabilities and expected deteriorations. A
      respiration, pulse, and best motor response (RPM) score predicts survivability.
      Logistic function-generated survival probability estimates from 99,369 military
      age victims were assessed using calibration and discrimination statistics. The
      consensus building Delphi method was used to provide aggregate expert opinion on
      victim deterioration rates. The models were solved using linear programming. Rule
      based (not requiring software) protocols were determined using a greedy algorithm
      for Iraqi combat scenarios, and simulations enabled comparison of STM to the
      widely known Simple Triage and Rapid Treatment (START) method. RESULTS: RPM was
      an accurate predictor of survival probability, equivalent to the Revised Trauma
      Score and exceeding the Injury Severity Score. In 18 simulations, STM and STM
      rule-based protocols increased survivorship over START from 20% to an 18-fold
      increase. CONCLUSIONS: STM offers lifesaving and operational advantages for
      military-age victims of blunt, penetrating, and blast overpressure-like trauma.

PMID- 20055065
TI  - Nonbattle injury among deployed troops: an epidemiologic study.
AB  - (n = 150) Nonbattle injury (NBI) continues to be a leading cause of morbidity
      among troops currently deployed to Iraq and Afghanistan. To assess NBI incidence,
      impact, and risk factors, a survey was given to soldiers during mid- or
      postdeployment from Iraq, Afghanistan, and surrounding region, from January 2005
      through May 2006. Among 3,367 troops completing a survey, 19.5% reported at least
      one NBI, and 85% sought care at least once for their symptoms. Service component,
      rank, and unit type were among factors associated with differential NBI risk.
      Twenty percent stated that NBI resulted in back-up personnel being called or
      shift change to cover impacted duties, and among those reported having been
      grounded from flight status, a third were the result of NBI. NBI continues to be
      a problem in recent deployments, and given the findings on individual and
      potential operational impact indicators, NBI should be viewed as a primary force
      health protection problem.

PMID- 20055066
TI  - An evaluation of an initiative to improve Veterans Health Administration mental
      health services: broad impacts of the VHA's Mental Health Strategic Plan.
AB  - In federal fiscal year (FY) 2005 the Department of Veterans Affairs (VA)
      implemented the comprehensive Mental Health Strategic Plan (MHSP). This study
      used performance measures from six broad domains to examine changes in the
      overall delivery of mental health services in the VA since the implementation of
      the MHSP. Performance measures from fiscal year 2004, the year before
      implementation of the MHSP, were compared with measures from fiscal years 2005,
      2006, and 2007, the first 3 years of MHSP implementation. We combined
      heterogeneous performance measures within domains through the use of standardized
      scores or "z-scores." An overall improvement of 0.32 standardized units was
      observed from FY 2004 to FY 2007, representing moderate to large changes by
      conventional standards. The domains with the greatest improvement (>1.0 standard
      deviation units) from FY 2004 to FY 2007 were population coverage/access,
      outpatient care quality, economic performance (primarily efficiency), and global
      functioning. There was a 0.3 standard deviation decline in inpatient satisfaction
      and a slight increase in reliance on inpatient care. Overall improvement in VA
      mental health care was thus substantial and continuing.

PMID- 20055067
TI  - Prediction of caseness for mental pathology in Swiss conscripts: the Self-Screen
      Prodrome.
AB  - BACKGROUND: Basic military training (BMT) is an environment of higher stress
      levels than are encountered in civilian life. It may trigger mental disorders in
      predisposed individuals. To reduce BMT attrition because of mental problems a
      psychiatric assessment is part of the Swiss recruitment process. An initial
      screening survey that identifies vulnerable individuals will be useful to save
      both cost and effort when dealing with large populations, such as military
      draftees. Aims of this investigation are to verify the psychometric properties of
      the Self-Screen Prodrome (SPro), a newly developed, short screening tool for
      psychopathology, and to validate it against the Symptom Checklist-90-Revised (SCL
      90-R), a well-established self-assessment instrument. METHOD: A sample of 12,380
      male conscripts from the year 2003 were administered both the SPro and the SCL-90
      R. Vulnerability was operationalized using the "caseness" definition of the SCL
      90-R. RESULTS: Factor analysis demonstrated unidimensional scaling of the SPro,
      and this was supported by high internal reliability. Scores of nine or more
      symptoms on the SPro scale were found to successfully discriminate between SCL-90
      R positive and negative cases. It is thus an adequate measure of general
      psychopathology (caseness). The association of p = 0.77 between the SPro and the
      SCL-90-R Global Severity Index (GSI) clearly supports concurrent validity. Our
      data also demonstrated that the SPro can distinguish individuals with self
      reported mental health problems from those with no or few reported symptoms
      (cutoff > or = 9; sensitivity 89.3%; specificity 84.9%; AUC 0.942; CI 95% 0.935
      0.948). CONCLUSION: Though replication and further research are needed, the SPro
      scale may currently be a useful screening tool for initial screening in a two
      stage process of early detection of psychopathology.

PMID- 20055068
TI  - The effectiveness of acupuncture for chronic daily headache: an outcomes study.
AB  - With the increased incidence of migraine headaches noted in the military
      population it becomes imperative to find safe and effective treatment options for
      soldiers. Acupuncture may be one of those options. This pilot study used a
      standardized set of well-known acupuncture points over a predetermined time
      interval on 26 subjects suffering from chronic daily headache, the majority being
      migraineurs, and found a reduction in the frequency and intensity of their
      headaches. Headache calendars and validated measurements were compared 12 weeks
      before and 12 weeks after the acupuncture intervention. Results showed continued
      improvements 12 weeks after the last treatment. Traditionally, acupuncture
      treatments are individualized at each visit. However the absence of a
      standardized treatment regimen obstructs data reproducibility across the
      discipline. A standardized approach may be useful. Variations of these
      acupuncture points have been used in recent research studies for migraines and
      acupuncture for headaches for the past 2,000 years.

PMID- 20055069
TI  - The effects of alternative input devices and repeated exposures on the Test of
      Basic Aviation Skills (TBAS) performance.
AB  - The use of computer-based, psychomotor testing systems for personnel selection
      and classification has gained popularity in the civilian and military worlds in
      recent years. However, several issues need to be resolved before adopting a
      computerized, psychomotor test. The purpose of this study was to compare the
      impact of alternative input devices used for the Test Of Basic Aviation Skills
      (TBAS) as well as to explore the practice effects of the TBAS. In study 1,
      participants were administered the TBAS tracking tests once with a throttle and
      once with foot pedals in a classic test-retest paradigm. The results confirmed
      that neither of the input devices provided a significant advantage on TBAS
      performance. In study 2, participants were administered the TBAS twice with a 24
      hour interval between testing. The results demonstrated significant practice
      effects for all the TBAS subtests except for the dichotic listening tests.

PMID- 20055070
TI  - The effect of steroid treatment with inhaled budesonide or intravenous
      methylprednisolone on phosgene-induced acute lung injury in a porcine model.
AB  - Toxic industrial chemicals e.g., phosgene, are widely used as reactive
      intermediates in industrial processes. Inhalation exposure to these chemicals can
      result in life-threatening acute lung injury (ALI), to which no specific antidote
      exists. This study aimed to assess the potential benefit of steroids in treating
      phosgene induced ALI. Anesthetized pigs were instrumented, exposed to phosgene Ct
      2000 mg.min.m(-3) (Ct is the product of concentration [mg.m(-3)] x time [min]),
      and ventilated with intermittent positive pressure ventilation before being
      randomized to study part 1: treatment with intravenous glucose saline (20 mL) or
      methylprednisolone (12.5 mg.kg(-1) in 20 mL) 6 h postexposure or study part 2:
      treatment with inhaled glucose saline (2 mL) or budesonide (2 mL of 0.5 mg.mL(-1)
      solution) at 1, 6, 12, and 18 h postexposure. Biochemical parameters and animal
      physiology were monitored to 24 h postexposure. The results show no change in
      mortality, lung edema, or shunt fraction; however, some beneficial effects on
      cardiac parameters e.g., stroke volume, left ventricular stroke work, were noted.
      Steroids were neither beneficial nor detrimental in the treatment of phosgene
      induced ALI. This study does not support the use of steroids alone as a
      treatment, but their use in a combined therapy strategy should be investigated.

PMID- 20055071
TI  - Adenovirus serotype 14 pneumonia at a basic military training site in the United
      States, spring 2007: a case series.
AB  - Adenovirus, a frequent cause of mild respiratory disease in military trainees,
      can result in severe manifestations when outbreaks are caused by novel viral
      strains for which there is little pre-existing immunity. Twenty-five basic
      military trainees (BMTs) were hospitalized with adenovirus pneumonia from April
      1, 2007 through June 21, 2007. Clinical findings for 9 of these patients with PCR
      confirmed adenovirus serotype 14 were studied retrospectively. The clinical
      picture was characterized by cough (88.9%) and sputum production (77.8%). All
      trainees were febrile. Laboratory results showed 88.9% had normal white blood
      cell (WBC) counts, 66.7% with high monocytes, and 55.6% with low lymphocytes on
      differential. All had lobar pneumonia radiographically. One patient required the
      intensive care unit (ICU) and later expired. In conclusion, among hospitalized
      patients with the combination of fever, productive cough, normal WBC, a
      differential showing high monocytes and low lymphocytes in an immunocompetent
      young adult with lobar pneumonia warrants a high level of suspicion for
      adenovirus 14 pneumonia.

PMID- 20055072
TI  - Predicting marching capacity while carrying extremely heavy loads.
AB  - The objective of this study was to establish the best prediction for endurance
      time of combat soldiers marching with extremely heavy loads. It was hypothesized
      that loads relative to individual characteristics (% maximal load carry capacity
      [MLCC], % body mass, % lean body mass) would better predict endurance time than
      load itself. Twenty-three male combat soldiers participated. MLCC was determined
      by increasing the load by 7.5 kg every 4 minutes until exhaustion. The marching
      velocity and gradient were 3 km.h(-1) and 5%, respectively. Endurance time was
      determined carrying 70, 80, and 90% of MLCC. MLCC was on average 102.6 kg +/-
      11.6. Load expressed as % MLCC was the best predictor for endurance time (R2 =
      0.45). Load expressed as % body mass, as % lean body mass, and absolute load
      predicted endurance time less well (R2 = 0.30, R2 = 0.24, and R2 = 0.23,
      respectively). On the basis of these results, it is recommended to assess the
      MLCC of individual combat soldiers.

PMID- 20055073
TI  - Effects of backpack load on balance and decisional processes.
AB  - A dual-task method was employed to assess the effects of backpack carriage weight
      on 20 young adults' balance and rapid decision making. During two separate
      sessions, participants' balance was perturbed during 18, 60-second trials by
      altering visual and/or somatosensory conditions. Concurrent balance control and
      auditory choice-reaction task performance were assessed. Each participant wore an
      all-purpose, lightweight, individual, carrying equipment (ALICE) backpack
      containing a load equal to 30% of his/her body weight throughout one session.
      Within-subjects analyses revealed that carriage load disrupted balance control
      and degraded cognitive processes but only on trials that required executive,
      higher-level, mental processing. The magnitude of the effects of the backpack
      load on balance and cognitive performance was similar over 22 minutes of testing.
      Carriage load degrades both balance control and situational awareness of ROTC
      cadets.

PMID- 20055074
TI  - Ventricular fibrillation associated with use of synephrine containing dietary
      supplement.
AB  - As the prevalence of obesity increases in the United States, military personnel
      are turning to unregulated dietary supplements to aid in weight loss. Some of
      these supplements may cause more harm than benefit. We report the case of a 27
      year-old active duty female who experienced an episode of ventricular
      fibrillation associated with the use of a dietary supplement containing
      synephrine. Recommendations for both physicians and the military regarding
      monitoring the use of these substances by active duty personnel are then
      provided.

PMID- 20055075
TI  - Laparoscopic versus open inguinal hernia repair: Expeditionary Medical Facility
      Kuwait experience.
AB  - BACKGROUND: Inguinal hernia is a common surgical problem in the active duty
      population. The decision to perform a hernia repair in the traditional open
      manner versus a laparoscopic approach is somewhat controversial. Furthermore, the
      type of repair performed has not been analyzed in a systematic manner within an
      operational setting. METHODS: We retrospectively reviewed all inguinal hernia
      repairs performed at Expeditionary Medical Facility Kuwait (EMFK) over an 18
      month period, from April 2007 through October 2008. Operative times and time to
      return to duty were compared between active duty personnel undergoing open mesh
      repair and laparoscopic extraperitoneal inguinal hernia repair. RESULTS: One
      hundred seventy-six consecutive patients who underwent inguinal hernia repair by
      six different surgeons were analyzed. One hundred and four patients had an open
      repair and 72 patients underwent laparoscopic repair. The mean operative time was
      significantly longer in the laparoscopic group (20.2 minutes, p < 0.001). The
      mean time to return to duty was significantly shorter in the laparoscopic group
      (2.3 days, p = 0.008). CONCLUSIONS: Laparoscopic inguinal hernia repair is
      associated with longer operative times but shorter recovery periods. The
      laparoscopic approach may be a viable option for patients in the expeditionary
      setting.

PMID- 20055076
TI  - Radiology corner. Answer to last month's radiology case and image: apical
      hemothorax from gunshot wound producihg a pleural cap.

PMID- 20055077
TI  - A special issue on Lipid-based delivery systems (liposomes, lipid nanoparticles,
      lipid matrices and medicines).

PMID- 20055078
TI  - A note on regulatory concerns and toxicity assessment in lipid-based delivery
      systems (LDS).
AB  - Lipid-based Delivery Systems (LDS) has been the focus of potential strategies in
      drug delivery for several years. A great deal of work has been invested on how to
      exploit their biocompatible and biodegradable nature, in combination with their
      nanosize range in a profitable way in the field of nanomedicines. A number of
      drugs loaded in LDS have been already tested in vivo successfully. However, in
      vivo behaviour of nanosized materials differs from their bulk counterparts (and
      also change drug properties), mainly depending on the particular LDS
      physicochemical characteristics. These may have huge impact on the toxicity of
      the system, despite the physiological nature of the lipid materials. This note on
      the regulatory concerns and toxicity assessment in LDS suggests that current
      knowledge of public and scientific communities is lacking, requiring intensive
      research and policy measures to provide a deep understanding on toxicological
      risks.

PMID- 20055079
TI  - Lipid nanomedicines for anticancer drug therapy.
AB  - More than half of all people diagnosed with cancer receive chemotherapy.
      Unfortunately, most chemotherapy drugs cannot tell the difference between a
      cancer cell and a healthy cell. In this sense, some other drawbacks often
      encountered with antineoplastic compounds, such as poor stability and specificity
      and a high occurrence of drug-resistant tumor cells may be overcome to some
      degree by incorporating them into drug delivery systems. Solid Lipid
      Nanoparticles (SLN) have arisen considerable interest in recent years. These are
      particles of submicron size made from a lipid matrix that is solid at room and
      body temperature. Moreover, the biodegradable and biocompatible nature of SLN
      makes them less toxic than other nanoparticulate systems. SLN are capable of
      encapsulating hydrophobic and hydrophilic drugs, and they also provide protection
      against chemical, photochemical or oxidative degradation of drugs, as well as the
      possibility of a sustained release of the incorporated drugs. Along with these
      last issues, the feasibility of scaling up for large scale production and the low
      cost of lipids as compared to biodegradable polymers or phospholipids have
      favoured their use as potential drug delivery systems. This review focuses on the
      recent advances in SLN as carriers for chemotherapeutic agent delivery.

PMID- 20055080
TI  - Lipid nanoparticles for drug delivery to the brain: in vivo veritas.
AB  - The present article is not aimed at extensively reviewing the literature on lipid
      nanoparticles, already described in monographs of recent redaction, but will
      provide a compilation of in vivo evidences supporting their potentiality in
      overcoming the blood-brain barrier problem. The advantages of using lipid over
      polymer carriers will be also discussed.

PMID- 20055082
TI  - Complement: alive and kicking nanomedicines.
AB  - Administration of liposome- and polymer-based clinical nanomedicines, as well as
      many other proposed multifunctional nanoparticles, often triggers
      hypersensitivity reactions without the involvement of IgE. These anaphylactic
      reactions are believed to be secondary to activation of the complement system,
      giving rise to the release of anaphylatoxins C3a and C5a that initiate a wide
      array of responses through their effect on mast cells, polymorphonuclear cells,
      platelets and monocytes. Additionally, the terminal complement C5b-9 complex
      induces platelet activation, thereby enhancing their procoagulant activity, and
      has the capacity to elicit non-lytic stimulatory responses from vascular
      endothelial cells. Here we discuss the molecular basis of complement activation
      by liposomes, including poly(ethylene glycol) coated vesicles, and other related
      lipid-based and phospholipid-poly(ethylene glycol) conjugate stabilized entities.
      We have further considered the role of these complement activating entities in
      experimental oncology since intra-tumoural complement activation is suggested to
      induce tumour growth and progression.

PMID- 20055083
TI  - Microemulsions and nanoemulsions: novel vehicles for whitening cosmeceuticals.
AB  - For Asian women, white skin is preferable. During the last decade, skin whitening
      products appear to be the largest and continually growing segment in skin-care
      market in Asia and have an impaction of economic worth. Skin whitening or
      lightening agents are as cosmetics which act as a drug-like benefit since melanin
      producing process of the skin is disturbed and can be classified as
      cosmeceuticals. To increase efficiency, novel vehicles are necessary for skin
      penetration enhancement of these agents. Microemulsions and nanoemulsions are one
      of useful nanocarriers for skin application in view of achieving efficiency of
      the active substances. Moreover, they can be formulated with ease for active
      ingredient incorporation, high stability and good appearance. In this review
      article, applications of well-known whitening or lightening agents were
      summarized. In addition, the use of microemulsions and nanoemulsions as novel
      vehicles for whitening products were discussed.

PMID- 20055081
TI  - Self-assembled lipid nanomedicines for siRNA tumor targeting.
AB  - Lipid-based nanoparticle technology has developed from chemical drug carrier into
      an efficient multifunctional siRNA tumor targeting delivery system. In this
      review, we start with an overview of the lipid-based nanomedicine history and the
      two classes of lipidic vectors for DNA or siRNA delivery. Then we discuss the
      features of lipid-based nanomedicine that lead to effective tumor targeting and
      the principles behind. We also discuss nanoparticle surface modification, classes
      of tumor targeting ligands, and other state-of-the-art strategies for enhancing
      endosome release primarily focused on lipid-based systems. At the end, we show
      that multifunctional self-assembled lipid-based nanoparticles could also be
      versatile delivery vehicles for cancer molecular imaging probes.

PMID- 20055084
TI  - Size determinations of colloidal fat emulsions: a comparative study.
AB  - Size and size distributions of colloidal dispersions are of crucial importance
      for their performance and safety. In the present study, commercially available
      fat emulsions (Lipofundin N, Lipofundin MCT and Lipidem) were analyzed by photon
      correlation spectroscopy, laser diffraction with adequate submicron
      instrumentation (Mastersizer 2000, Coulter LS 13 230) and by asymmetrical flow
      field-flow fractionation combined with multi-angle laser light scattering. The
      separation capacity of the field-flow fractionation system and accuracy of size
      determination by multi-angle laser light scattering was checked with mixtures of
      monodisperse polystyrene nanospheres. In addition, the ultrastructure of
      Lipofundin N and Lipofundin MCT was investigated by cryo-electron microscopy. All
      different particle sizing methods gave different mean sizes and size
      distributions but overall, results were in reasonable agreement. By all methods,
      a larger mean droplet size (between 350 and 400 nm) as well as a broader
      distribution was measured for Lipofundin N compared to Lipofundin MCT and Lipidem
      (mean droplet size between about 280 and 320 nm). Size distributions of
      Lipofundin MCT and Lipidem were very similar but a slightly smaller size was
      indicated by all methods for Lipidem. Sub-micron resolution was best in the
      Coulter LS but the fraction of larger particles in the upper nm-range was
      presumably underestimated. The emulsions could be analyzed in a highly
      reproducible manner by asymmetrical flow field-flow fractionation coupled with
      multi-angle laser light scattering and this method appears very promising
      particularly with regard to the separation and/or collection of sample fractions
      being homogeneous in size.

PMID- 20055085
TI  - Biocompatible microemulsions for fabrication of glyceryl monostearate solid lipid
      nanoparticles (SLN) of tretinoin.
AB  - The objective of the present investigation was to fabricate glyceryl monostearate
      SLN by employing a biocompatible microemulsion as a template. Biocompatible
      excipients such as Tween 20 (as a surfactant) and Transcutol P (a cosourfactant)
      (at different K(m) ratios) were selected for the fabrication of microemulsions.
      Pseudo-ternary phase diagrams were plotted to identify the area of the
      microemulsion existence. Glyceryl monostearate SLN were fabricated by dispersing
      the microemulsion (maintained at 65 degrees C) into cold water (maintained at 2-3
      degrees C). The particle size of the SLN was determined by photon correlation
      spectroscopy. Tretinoin, a lipophilic anti-acne agent was incorporated into SLN
      as a model drug. The encapsulation efficiency of tretinoin in the SLN was
      determined by using Nanosep ultrafilteration device at different lipid loads viz.
      1%, 1.5% and 2%. Glyceryl monostearate SLN fabricated from biocompatible
      microemulsion template exhibited average particle size of 175 nm and
      polydispersity index of 0.833. Tretinoin could be successfully incorporated into
      SLN and the encapsulation efficiency ranged from 37-48% at different lipid loads.

PMID- 20055086
TI  - Analysis of protein physical stability in lipid based delivery systems--the
      challenges of lipid drug delivery systems.
AB  - Lipid based systems are a promising delivery system for many drug molecules,
      including labile compounds such as peptides and proteins. However, in the
      development of these systems the effect on the physical stability is rarely taken
      into account. Physical changes are often correlated with changes in biological
      activity but are generally much easier to assess. The present paper illustrates
      the use of a combination of techniques, differential scanning calorimetry (DSC),
      Fourier transform infrared spectroscopy (FTIR), and intrinsic tryptophan
      fluorescence, to determine structural changes of proteins in lipid based systems
      such as solid lipid nanoparticles and emulsions.

PMID- 20055087
TI  - Haemolytic activity of liposomes: effect of vesicle size, lipid concentration and
      polyethylene glycol-lipid or arsonolipid incorporation.
AB  - The haemolysis caused by various types of liposomes was measured after incubation
      of liposomes with human red blood cell (erythrocyte) suspension. Liposomes
      composed of phospholipids and containing or not arsonolipids (arsonoliposomes)
      were tested. In some cases liposomes that were coated with polyethylene glycol
      (MW 2000), which were formulated by including 8 mol% DSPE-PEG2000 in their lipid
      membrane, were used. Multilamellar vesicles were prepared by the thin film
      hydration technique (conventional liposomes) or by the one-step technique
      (arsonoliposomes). Sonicated vesicles were produced by probe sonication of the
      initial liposome preparations. Phospholipid concentration in the liposome
      dispersions were measured by the Stewart assay, and adjusted accordingly.
      Haemolysis was measured after incubating 100 microl of liposome dispersions with
      900 microl of red blood cell suspension (blood) for 1 h. The results reveal that
      the haemolysis caused, when liposomes are incubated in blood at concentrations
      below 0.16 mg (lipid)/ml (blood), was minimum. Only in case of Pegylated
      arsonoliposomes, significant haemolysis percents were observed. At higher lipid
      concentrations, 0.38 or 0.6 mg/ml, the haemolysis caused by arsonoliposomes was
      substantially increased, even in the cases of non-Pegylated arsonoliposomes. In
      most cases, especially when arsonolipid-containing liposomes were evaluated,
      vesicle size also had considerable effect on vesicle-induced haemolysis.
      Nevertheless, at concentrations which are relevant with liposomal drug
      administration in humans, all formulations tested demonstrated negligible
      haemolysis.

PMID- 20055088
TI  - Interaction of fullerenes C60 with large unilamellar vesicles.
AB  - In order to explore the fullerene-lipid interaction, we have studied the effects
      caused by C60 on Large Unilamellar Vesicles (LUV). For this purpose liposomes
      composed of L-a Phosphatidylcholine (PC) and 1,2-dimyristoyl-sn-glycero-3
      phospocholine (DMPC) and Cholesterol (Chol) in 2:1 molar ratio were used. The
      dispersions were characterized by means of Dynamic Light Scattering (DLS), zeta
      potential measurements and Differential Scanning Calorimetry studies (DSC). The
      incorporation of C60 into liposomes altered their physicochemical properties. A
      reduction to the mean diameter of the liposomes was observed when C60 were
      incorporated, which might imply deformations on the lipid membrane induced by
      fullerenes. An increase to the surface charge of the liposomes was noticed when
      C60 molecules were present in the membrane providing evidence of their successful
      incorporation into the liposomal bilayers. Finally the miscibility of liposomes
      with C60 was investigated by DSC. Alterations occurred to the main transition of
      the liposomes when C60 molecules were present in the membrane might be attributed
      to the penetration of the carbonaceous material into the lipid bilayers.

PMID- 20055089
TI  - The effect of geometric shape on the release properties of metronidazole from
      lipid matrix tablets.
AB  - In this study, the lipophilic matrix tablets of metronidazole were prepared with
      Cutina HR (hydrogenated castor oil), stearic acid, Compritol ATO 888 (glyceryl
      behenate) and Precirol ATO 5 (glycerol palmitostearate) in two different shapes;
      cylinder and hexagonal. Our first aim was to investigate the influence of the
      lipid excipients and geometric shape on the release behavior of metronidazole,
      and the second aim was to investigate the influence of tablet surface area/volume
      (SA/V) ratio on drug release from controlled release matrix tablets. In vitro
      release test was performed using a standard USP dissolution apparatus I.
      Hardness, surface/volume ratio and friability were determined. The hexagonal
      tablets were harder than the cylinder tablets. Stearic acid showed the highest
      release rates for both geometric shapes reflecting the highest surface area and
      the lowest SA/V ratio. According to power law analysis, the diffusion mechanism
      was expressed as a Fickian diffusion for all lipid matrix tablets. The square
      root of time relationship was operative for all tablets. Higuchi kinetic
      constants obtained with hexagonal tablets were higher than the cylinder tablets.
      As the type of lipid matrix, the geometric shape of the tablets was also
      effective on the diffusion and release kinetics. From the present study, it was
      shown that surface area and volume ratio may be used as parameters for the
      evaluation of the drug release profile.

PMID- 20055090
TI  - Silver-nanolipid complex for application to atopic dermatitis skin: rheological
      characterization, in vivo efficiency and theory of action.
AB  - A skin care formulation was developed by incorporating microsilver, in
      combination with nanostructured lipid carriers (NLC) into an o/w cream and
      lotion. To increase skin adhesion of the NLC, and subsequent film formation and
      occlusion onto the skin, the NLC were produced with a size of about 200 nm.
      Production of NLC was performed by high-pressure homogenisation. Characterization
      was performed regarding size and charge (zeta potential), and for the cream and
      lotion also by rheology. Incorporation of NLC and/or microsilver into the cream
      or lotion led to pronounced changes in the thixotropic behaviour (shape of
      rheogram, yield point, viscosity). This was explained by specific interaction of
      the nanoparticles and/or the microsilver with the two formulations. In vivo
      studies revealed a high potential to remove not only symptoms of irritated
      sensitive skin, but also of light to medium atopic dermatitis. Based on zeta
      potential measurements, a silver ion-nanolipid complex seems to form which leads
      to a higher activity of the antimicrobial silver, e.g., increasing the silver ion
      concentration on skin and bacterial membranes. The antimicrobial effect in
      combination with restoration of normal skin condition (repair of stratum corneum
      lipid film by NLC) is obviously sufficient to replace in many cases medical
      therapy with glucocorticoids by a biological, natural skin care cosmetic nano
      formulation.

PMID- 20055091
TI  - Dermal and ocular safety of the new phospholipase A2 inhibitors PX-18 and PX-13
      formulated as drug nanosuspension.
AB  - PX-18 and PX-13 are new secreted phospholipase A2 inhibitors. An increased
      expression of secreted phospholipase A2 in psoriatic epidermis and dermis was
      reported in the literature, hence the dermal application of PX-18 and PX-13 seems
      to be a promising approach for psoriasis treatment. Both compounds are
      practically insoluble in aqueous media and hard to formulate using conventional
      techniques. Therefore, nanosuspensions were prepared by high pressure
      homogenization. Pre-clinical skin and eye irritation tests were performed with PX
      18 and PX-13 bulk material and 5% (w/w) PX-18 and PX-13 nanosuspensions using the
      EPISKIN and the HET-CAM test to aid safety assessment and to facilitate the
      design of safe and efficient human studies. It could be shown that
      nanosuspensions with an active content of 5% (w/w) with a particle size well in
      the nanometer range can be produced applying high pressure homogenisation. The
      results of the EPISKIN test allow the classification of PX-18 and PX-13 bulk
      material and the according nanosuspensions as non irritant to the skin. According
      to the test protocol applied for the HET-CAM test, the bulk material of the new
      secreted phospholipase A2 inhibitors as well as the nanosuspensions can be
      classified as non/slightly irritant to the eye.

PMID- 20055092
TI  - Liposomal nanocarriers for tumor imaging.
AB  - Currently used imaging modalities such as scintigraphy, computed tomography,
      magnetic resonance imaging and ultrasonography require the sufficient intensity
      of a corresponding signal from an area of interest to differentiate this area
      from the surrounding tissues. Targeting of various reporter moieties directly to
      the specific organs, tissues or tumors provide the highest dose of drug directly
      where it is needed. Many different types of nanoparticles are currently being
      studied for applications in nanomedicine. Among particulate drug carriers,
      liposomes are one of the most extensively studied and possess the most suitable
      characteristics for encapsulation of many drugs, genes, and diagnostic (imaging)
      agents. Among the many potential targets for such nanocarriers, tumors have been
      most often investigated. This review attempts to summarize the currently
      available information regarding liposomal nanocarriers for cancer imaging.

PMID- 20055093
TI  - Development of idarubicin and doxorubicin solid lipid nanoparticles to overcome
      Pgp-mediated multiple drug resistance in leukemia.
AB  - The objectives of these studies were to investigate and compare solid lipid
      nanoparticles (SLNs) of two anthracyclines, idarubicin (IDA) and doxorubicin
      (DOX), against Pgp-mediated multiple drug resistance (MDR) in-vitro and in-vivo
      using different human and murine cancer cell models. IDA and DOX SLNs were
      developed from warm microemulsion precursors comprising emulsifying wax as the
      oil phase, and polyoxyl 20-stearyl ether (Brij 78) and D-alpha-tocopheryl
      polyethylene glycol succinate (Vitamin E TPGS) as the surfactants. Anionic ion
      pairing agents, sodium taurodeoxycholate (STDC) and sodium tetradecyl sulfate
      (STS), were used to neutralize the charges of the cationic anthracyclines and
      enhance entrapment of the drugs in the SLN. The in-vitro cytotoxicity results
      showed that the IC50 value of DOX NPs was 9-fold lower than that of free DOX
      solution in resistant P388/ADR cell line. In contrast, free IDA had comparable
      IC50 values as IDA NPs in Pgp-overexpressing P388/ADR and HCT-15 cells. In the in
      vivo P388/ADR leukemia mouse model, the median survival time of DOX NPs was
      significantly greater than that of free DOX, and controls. In contrast, free IDA
      was equally as effective as IDA NPs in P388 and Pgp-overexpressing HCT-15 mouse
      tumor models. The cell uptake of IDA formulated as free IDA and IDA NPs was
      comparable in Pgp-overexpressing cells. In conclusion, DOX NPs could overcome Pgp
      mediated MDR both in-vitro in P388/ADR leukemia cells and in-vivo in the murine
      leukemia mouse model. The present study suggests that our SLNs may offer
      potential to deliver anticancer drugs for the treatment of Pgp-mediated MDR in
      leukemia; however, selection of target drug may be very important.

PMID- 20055094
TI  - Ionically crosslinked chitosan nanoparticles as gene delivery systems: effect of
      PEGylation degree on in vitro and in vivo gene transfer.
AB  - The purpose of this work was to develop a new type of nanoparticles made of PEG
      grafted chi-tosans (CS-g-PEG) using tripolyphosphate (TPP) as a polyanionic
      crosslinker and to investigate the potential of these nanostructures as gene
      carriers. The formation of these nanoparticles was optimised by the evaluation of
      the combined effects of pH, PEGylation degree and chitosan/crosslinker ratio on
      the particle formation. The selected CS-g-PEG/TPP nanoparticles were studied with
      regard to their physico-chemical properties, DNA association efficiency as well
      as to their toxicity and gene expression in vitro. Furthermore, the best
      performing nanoparticle prototypes were also evaluated for their potential for in
      vivo gene delivery. CS-g-PEG/TPP nanoparticles displayed a high DNA association
      efficiency combined with high stability and low cellular toxicity. The results of
      the in vitro transfection assays showed positive effects of the PEGylation in the
      case of particles prepared from high molecular weight chitosan, while the
      presence of PEG slightly decreased the efficiency of the nanoparticles based on
      low molecular weight chitosan. Overall, high and long lasting gene expression
      levels could be observed for all types of nanoparticles. Moreover, CS-g-PEG/TPP
      nanoparticles also mediated high gene expression levels in vivo, following nasal
      administration. These results indicate the potential of ionically crosslinked CS
      g-PEG/TPP nanoparticles as transmucosal gene delivery systems.

PMID- 20055095
TI  - Aminodextran containing magnetite nanoparticles for molecular biology
      applications: preparation and evaluation.
AB  - Within the framework of medical diagnosis, the main objective is the development
      of hydrophilic magnetic particles for the generic capture of the nucleic acids in
      order to enhance the sensitivity. The strategy used in this work is based on the
      synthesis of cationic and hydrophilic magnetic nanoparticles bearing
      aminodextran. The synthesis was performed using two different processes: (i)
      coprecipitation of the ferrous and ferric salts in the presence of an aqueous
      solution of aminodextran and (ii) via adsorption of aminodextran on iron oxide
      nanoparticles. The obtained particles are characterized and evaluated in non
      specific nucleic acids extraction and amplification.

PMID- 20055096
TI  - Size-uniform 200 nm particles: fabrication and application to magnetofection.
AB  - We report on the fabrication of arrays of mono- and multimetallic particles via
      metal evaporation onto lithographically patterned posts, as well as the magnetic
      force calibration and successful magnetofection of iron particles grown via this
      method. This work represents the first instance in which metal evaporation onto
      post structures was used for the formation of released, shape-defined metal
      particles. Also, our work represents the first use of lithographically defined
      particles as agents of magnetofection. Using these techniques it is possible to
      create particles with complex shapes and lateral dimensions as small as 40 nm.
      Our demonstrated compositionally flexible particles are highly size-uniform due
      to their photolithographically defined growth substrates, with particle
      dimensions along two axes fixed at 200 nm; the third axis dimension can be varied
      from 20 nm to 300 nm during the deposition procedure. Atomic percent of metals
      incorporated into the particle volume is highly tunable and particles have been
      synthesized with as many as four different metals. We performed magnetic force
      calibrations on a single particle size for iron particles using an axially
      magnetized NeFeB permanent magnet and comparisons are made with commercially
      available magnetic beads. In order to evalutate their usefulness as
      magnetofection agents, an antisense oligonucleotide (ODN) designed to correct the
      aberrant splicing of enhanced green fluorescent protein mRNA, was successfully
      transfected into a modified HeLa cell line. Magnetically enhanced gene delivery
      was accomplished in vitro using antisense ODN-laden iron particles followed by
      application of a field gradient. Magnetically enhanced transfection resulted in a
      76% and 139% increase in fluorescence intensity when compared to Lipofectamine
      and antisense ODN-loaded particles delivered without magnetic treatment,
      respectively. To our knowledge, these experiments constitute the first use of
      lithographically defined particles as successful agents for magnetically enhanced
      transfection of an antisense oligonucleotide.

PMID- 20055097
TI  - Nanocytotoxicity: violacein and violacein-loaded poly (D, L-lactide-co-glycolide)
      nanoparticles acting on human leukemic cells.
AB  - Violacein is a compound obtained from Chromobacterium violaceum, a bacterium
      found in the Amazonian region. Violacein-loaded poly (D, L-lactide-co-glycolide)
      nanoparticles has a similar inhibitory effect evaluated by trypan blue assay on
      leukemic HL60 cells than the free form. However, the cytotoxic effects evaluated
      by phosphatase activity and MTT reduction assays were lower for the encapsulated
      form than for free violacein. Based on morphological changes, violacein and
      violacein entrapped in nanoparticles were found to induce terminal
      differentiation (assessed by nitro blue tetrazolium reduction) in HL60 cells.
      Thus, both formulations inhibit HL60 cell growth in vitro, partly by inducing
      cytotoxic effects and cell differentiation. Flow cytometric analysis of HL60
      cells after treatment for 12 h showed that violacein-loaded PLGA induced
      apoptosis, with maximum cell death at a concentration of 2 microM. Violacein and
      violacein/PLGA induced opposite effects on the mitochondrial swelling which
      indicates altered mitochondrial function. The mitochondrial activity was also
      checked by flow cytometry studies. Labelled cells with the probe JC1 displayed a
      basal hypopolarized status of the mitochondria in treated cells. Based on
      morphological changes, alterations in phospholipid asymmetry and changes in
      mitochondrial polarization, violacein and nanoparticles containing violacein were
      found to trigger cell death by apoptosis. These methodologies are promising as
      diagnostic and mechanistic effects of nanoparticles in cell cultures.

PMID- 20055098
TI  - Characterization and cytotoxicity of self-organized assemblies of curcumin and
      amphiphatic poly(ethylene glycol).
AB  - Polymer-conjugated nanoparticles are an important technology to control the
      stability, safety, and efficacy in drug delivery systems. Herein, we investigate
      self-organized mixed assemblies of a lipophilic drug candidate, curcumin (Cm),
      and a poly(oxyethylene) cholesteryl ether (PEG-Chol). Cm was assembled together
      with PEG-Chol to form nano-sized assemblies (around 10 nm) of assumed micelles.
      In contrast with the rapid decomposition of free Cm due to the hydrolysis, the Cm
      was highly stabilized in the nanoparticles, especially at below 40 mol% Cm. Cell
      viability assay revealed that the cytotoxic activity of the Cm/PEG-Chol
      nanoparticles against myeloma cells is higher than those of free Cm in a
      comparison at 1 microM. On the other hand, both the Cm/PEG-Chol nanoparticles and
      PEG-Chol micelles had significant cytotoxicity to the myeloma cells at 5 microM.
      Taken together, the present Cm/PEG-Chol system offers a stable nanoparticle
      encapsulating Cm which can be injected as a liquid. Cm and vehicle micelles will
      damage the cancer cells cooperatively.

PMID- 20055099
TI  - Antibacterial effects of silver nanoparticles on the bacterial strains isolated
      from catheterized urinary tract infection cases.
AB  - Urinary tract infections (UTI) are among the most common type of nosocomial
      infections. Patients with indwelling urinary catheters are at the highest risk of
      getting infected. The antibacterial effects of silver compounds have been known
      to man kind for ancient times. It has recently been found that silver
      nanoparticles possess significant antibacterial potential. Surface modifications
      of urinary catheters with Ag-NPs may prevent the risk of contamination and the
      associated infections. In this study we have studied the antibacterial effects of
      Ag-NPS on bacterial isolates from UTI cases. Our results suggest possible utility
      of Ag-NPs as coating agent.

PMID- 20055100
TI  - Iron oxide/niobium oxide core-shell magnetic nanoparticle-based phosphopeptide
      enrichment from biological samples for MALDI MS analysis.
AB  - The feasibility of using niobium oxide-coated magnetic nanoparticles (NPs) as
      affinity probes for selectively trapping phosphopeptides from peptide mixtures
      including tryptic digest of caseins, serum, and cell lysate was demonstrated in
      this study. Phosphopeptide enrichment was rapid when subjecting these systems to
      microwave heating for 1 min; the probe-target species, which were readily
      isolated through magnetic separation, were then analyzed using matrix-assisted
      laser desorption/ ionization mass spectrometry (MALDI MS). Only signals for
      phosphopeptides were present in the resulting mass spectra. The detection limit
      for monophosphopeptide was as low as 5 fmol.

PMID- 20055101
TI  - Solid lipid nanoparticles for topical administration of Kaempferia parviflora
      extracts.
AB  - Extracts of Kaempferia parviflora (KP) were formulated in solid lipid
      nanoparticles (SLNs) in order to enhance their transdermal permeability. The KP
      extracts were entrapped within SLNs by adding them to a melted mixture of oils,
      surfactants and PEGylating agents and subsequently forming an oil-in-water
      microemulsion at an elevated temperature. Cooling of this microemulsion resulted
      in the formation of SLNs. The formulation with the optimum properties was
      composed of stearyl alcohol as the nanoparticle matrix and Tocopheryl
      Polyethylene Glycol Succinate (TPGS) as the surfactant. Particle sizes of 82-108
      nm were obtained with entrapment efficiencies as high as 87%. The release of the
      flavonoids from the SLN matrix was measured after suspending them in a Phosphate
      Buffered Saline (PBS)/Tween 80 solution and demonstrated biphasic patterns.
      Permeability studies using a skin model composed of human-derived epidermal
      keratinocytes were conducted in which a topically applied KP extract-loaded SLN
      was compared to a KP-hydroxypropyl methylcellulose/Tween 80 gel formulation
      containing KP extract. The amount of total KP flavonoids in the SLNs and gel that
      had permeated through the skin after 25 hours (95.57 +/- 9.08 and 81.04 +/- 5.82
      g, respectively) were found to be significantly different (P < 0.05). In
      addition, the flux values of three of the flavonoids were greater when
      incorporated in SLNs.

PMID- 20055102
TI  - Electrospinning: methods and development of biodegradable nanofibres for drug
      release.
AB  - It is clear that nanofibrous structures can be used as tools for many
      applications. It is already known that electrospinning is a highly versatile
      method of producing nanofibres and recent developments in the technique of
      electrospinning have led to the development of aligned nanofibres and biphasic,
      core-sheath fibres which can be used to encapsulate different materials from
      molecules to cells. Natural extracellular matrix (ECM) contains fibres in both
      micro and nano-scales and provides a structural scaffold which allows cells to
      localize, migrate, proliferate and differentiate. Polymer nanofibres can provide
      the structural cues of ECM. However, current literature gives new hope to further
      functionalising polymeric nanofibres by using them for drug delivery devices and
      improving their design to improve control of delivery. By encapsulating active
      agents within nanofibres (multifunctional nanofibres), a degree of control can be
      exerted over the release of encapsulated agents and therefore, the behaviour of
      cells can be manipulated for developing effective therapies and is extremely
      encouraging in the tissue engineering field by combining factors like fibre
      diameter, alignment and chemicals in new ways. Such multifunctional nanofibre
      based systems are already being investigated in vivo. Experiments have shown the
      significant potential for treatments of disease and engineering of neural and
      bone tissues. Further, phase III clinical trials of nanofibrous patches for
      applications in wound treatment were encouraging. Hopefully, clinical
      applications of these drug delivery devices will follow, to enhance regenerative
      medicine applications.

PMID- 20055103
TI  - Current status of nanoparticle-based imaging agents for early diagnosis of cancer
      and atherosclerosis.
AB  - Endothelium plays a vital role in various vascular functions, and its dysfunction
      is a key underlying process closely related to diverse array of diseases such as
      atherosclerosis and tumor. Therefore, early detection of endothelial dysfunction
      at the functional or molecular level is of high importance for effective therapy.
      Recent advances in nanotechnology and our understanding in cellular and molecular
      biology have provided various biomedical imaging modalities and nanosized
      multimodal imaging agents. Multimodal nanoparticles that encompass the targeting
      ligands and magnetic/optical imaging labels enable us to visualize the
      pathophysiological process of various diseases using multiple imaging techniques.
      To visualize the specific pathogenic process at the molecular level, the imaging
      probe needs to be surface-functionalized with specific affinity ligands such as
      monoclonal antibodies (mAb). Combining the functional imaging agents along with
      therapeutic drugs has great potential for effective early detection, accurate
      diagnosis, and treatment of disease. The current review will highlight the
      application of various nanoparticle-based imaging agents and their recent
      developments in diagnosing endothelium dysfunction with a special emphasis on
      atherosclerosis and cancer.

PMID- 20055104
TI  - Challenges and potential for RNA nanoparticles (RNPs).
AB  - The current research of our group focuses on delivery of oligonucleotides and
      gene vaccines targeted against infectious disease and cancer. Recently we
      reported a strategy for associating DNA to gold via protamine delivery enhancing
      material which here we suggest might be applicable to RNA and to other
      nanoparticles. An important new modality for such RNA based nanoparticles (RNPs)
      is the myriad of genes now known to undergo alternative splicing. Here we will
      review some important issues for the binding, stabilization and delivery of RNA,
      particularly splice-site switching oligomers (SSOs) via these RNPs in order to
      achieve selective molecular therapeutic effects and unlock their potential as
      chemotherapeutic agents.

PMID- 20055105
TI  - Insulin-loaded PLGA nanoparticles for oral administration: an in vitro physico
      chemical characterization.
AB  - The aim of this work was to study poly(d,l-lactic-co-glycolic) acid (PLGA)
      nanoparticles--formulated by a modified solvent diffusion technique--applied as
      model nanocarriers for insulin in potential oral administrations. These
      nanostructures consisted of a blend matrix formed by PLGA copolymer and
      polyoxyethylene derivatives. Two types of blend formulations, PLGA:poloxamer
      (Pluronic F68) and PLGA:poloxamine (Tetronic T904), were analyzed, and the
      results compared to those obtained with pure PLGA nanoparticles. The work has
      been divided into two parts. (a) Firstly, the stability of the unloaded
      nanoparticles in simulated gastric and intestinal fluids was studied. Degradation
      studies reflected a strong interaction between the pure PLGA nanoparticles and
      the digestive enzymes. However, this interaction was considerably reduced in the
      blend formulations, although the PLGA:poloxamine system became colloidally
      unstable in the simulated gastric fluid. (b) Secondly, the effect of the net
      charge of the encapsulated macromolecule in the final properties of the blend
      formulations was studied by encapsulating insulin below and above its
      corresponding isoelectric point. The net charge of the encapsulated protein
      showed a clear effect in the final size of the nanoparticles, while the
      encapsulation efficiency was controlled by the polyoxyethylene derivative
      presents in the blend formulation. The obtained results show that those carriers
      formed with encapsulated insulin in PLGA-Pluronic F68 particles are capable, at
      least in vitro, to overcome the gastrointestinal barrier. Therefore, these
      nanocarriers seem to be appropriate for oral administration of insulin, although
      performing in vivo studies becomes necessary to corroborate such statement.

PMID- 20055106
TI  - Enhanced multicolor resonant-optical-assay with direct text output.
AB  - The effectiveness of a novel multicolor biochip boosted by reducing cluster
      repulsion and in-situ silver enhancement has been demonstrated by using anti
      serum albumine antibodies conjugated to gold nanoparticles on a vacuum metalized
      plastic film coated with nano-resonance driving ceramic multilayers. A dense and
      smooth vacuum deposited SiO approximately 1.6 top layer (50 to 300 nm thick) on a
      flexible thermoplastic polymer poly-ethylene-terephthalate-chip functionalized
      via poly-ethylenimine monolayer coating and chemical cross-linking was employed
      to immobilize capture antibodies. Following capturing of the human serum albumin
      antigen from analyte solution, the multicolor chip reacts with anti HSA-gold
      nanoparticles binding them in a nanometric distance to the resonant mirror of the
      device-visible to the eye as faint coloring of the chip surface. Following silver
      enhancement, a strong metallic angle-dependent color via Resonance Enhanced
      Absorption is observed. In this study, silver staining has been used for the
      first time to boost and shift the color of nano-resonance enhanced optical
      bioassays. The use of silver staining increases and significantly modifies the
      intensity of the resonance color and was done in less than 5 minutes directly on
      the chip. This novel methodology will find broad application in Point-of-Care
      diagnostic devices via a color signal output designed as a written text with high
      contrast to replace standard lateral flow devices just showing lines or dots.

PMID- 20055107
TI  - Development and evaluation of nitrendipine nanoemulsion for intranasal delivery.
AB  - The clinical efficacy of Nitrendipine (NDP), a potent antihypertensive molecule,
      is limited due to its low oral bioavailability (10% to 20%) resulting from its
      extensive first-pass metabolism. The purpose of the present investigation was to
      enhance the bioavailability of NDP through formulating a nanoemulsion for its
      intranasal delivery. A Caproyl 90 based nanoemulsion sytem with Tween 80 as the
      surfactant, Transcutol P and Solutol HS-15 as solubiliser and cosurfactant
      respectively, was developed. A single isotropic region, which is considered as a
      bicontinuous nanoemulsion, was identified in the pseudo-ternary phase diagrams
      developed at various Tween 80: Transcutol P: Solutol HS-15 ratios. NDP was
      solubilized in a system consisting of Tween 80: Transcutol P: Solutol HS-15 at
      1:2:1 weight ratio. The developed nanoemulsion was safe for nasal administration
      as confirmed by nasal histopathlogy studies with the mean globule size of 98.50
      nm. The drug content per actuation was found to be 99.58 +/- 0.05%, with no
      significant changes over a period of one month. In vivo absorption studies
      revealed that NDP absorption from the nanoemulsion had a rapid onset of action
      and a relative bioavailability of 60.44%, significantly greater than the marketed
      oral tablets.

PMID- 20055108
TI  - Biodegradable polyphosphazene-nanohydroxyapatite composite nanofibers: scaffolds
      for bone tissue engineering.
AB  - Bone is a natural composite comprised of hierarchically arranged collagen
      fibrils, hydroxyapatite and proteoglycans in the nanometer scale. This
      preliminary study reports the fabrication of biodegradable poly[bis(ethyl
      alanato)phosphazene]-nanohydroxyapatite (PNEA-nHAp) composite nanofiber matrices
      via electrospinning. Binary solvent compositions of THF and ethanol were used as
      a spinning solvent to attain better nanohydroxyapatite dispersibility in PNEA
      solution. These nanocomposites were characterized for morphology, nHAp
      distribution and content using spectroscopy and gravimetric estimations.
      Composite nanofibers fabricated in the diameter range of 100-310 nm could
      encapsulate 20-40 nm nHAp crystals. A better composite nanofiber yield was
      obtained for 50% (w/w) nHAp experimental loadings. Incremental experimental
      loading beyond 60% (w/w) hindered electrospinning due to polymer-nHAp phase
      separation. Composites nanofibers had a rougher surface and nodules along the
      length of the fibers suggesting nHAp encapsulation. Further, characterization via
      energy dispersive X-ray spectroscopy and X-ray mapping confirmed the nHAp
      encapsulation. Providing cells with a natural bone like environment with a
      fibrillar structure and natural hydroxyapatite can enhance bone tissue
      regeneration/repair.

PMID- 20055109
TI  - Improving oral absorption of Salmon calcitonin by trimyristin lipid
      nanoparticles.
AB  - Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and
      poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the
      incorporation of Salmon calcitonin, and further explored as protein carriers for
      oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an
      association efficiency for calcitonin of approx. 86%. The morphology of SLN was
      investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth
      surface. The in vitro release of calcitonin occurred for a period of 8 h, under
      both gastric and intestinal simulated pH conditions, predicting suitable
      properties for oral administration. The pharmacological activity of the protein
      was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered
      the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining
      hypocalcaemia over 8 h. The results indicate that incorporation of Salmon
      calcitonin into trimyristin SLN is a key factor for the improvement of the
      efficiency of such carriers for oral delivery of proteins.

PMID- 20055110
TI  - Solid lipid nanoparticles as insulin inhalation carriers for enhanced pulmonary
      delivery.
AB  - Growing attentions have been paid to the pulmonary route for systemic delivery of
      peptide and protein drugs, such as insulin. Advantages of this non-injective
      route include rapid drug deposition in the target organ, fewer systemic side
      effects and avoiding first pass metabolism. However, sustained release
      formulations for pulmonary delivery have not been fully exploited till now. In
      our study, a novel dry powder inhalation (DPI) system of insulin loaded solid
      lipid nanoparticles (Ins-SLNs) was investigated for prolonged drug release,
      improved stability and effective inhalation. Firstly, the drug was incorporated
      into the lipid carriers for a maximum entrapment efficiency as high as 69.47 +/-
      3.27% (n = 3). Secondly, DPI formulation was prepared by spray freeze drying of
      Ins-SLNs suspension, with optimized lyoprotectant and technique parameters in
      this procedure. The properties of DPI particles were characterized for their
      pulmonary delivery potency. Thirdly, the in vivo study of intratracheal
      instillation of Ins-SLNs to diabetic rats showed prolonged hypoglycemic effect
      and a relative pharmacological bioavailability of 44.40% could be achieved in the
      group of 8 IU/kg dosage. These results indicated that SLNs have shown increasing
      potential as an efficient and non-toxic lipophilic colloidal drug carrier for
      enhanced pulmonary delivery of insulin.

PMID- 20055111
TI  - Antibacterial applications of silver nanoparticles synthesized by aqueous extract
      of Azadirachta indica (Neem) leaves.
AB  - Silver nanoparticles are known to have bactericidal effects. A new generation of
      dressings incorporating antimicrobial agents like silver nanoparticles is being
      formulated to reduce or prevent infections. The particles can be incorporated in
      materials and cloth rendering them sterile. Recently, it was found that aqueous
      silver ions can be reduced by aqueous extract of plant parts to generate
      extremely stable silver nanoparticles in water. Apart from being environmentally
      friendly process, use of Neem leaves extract might add synergistic antibacterial
      effect of Neem leaves to the biosynthesized nanoparticles. With this hypothesis
      the biosynthetic production of silver nanoparticles by aqueous extract of Neem
      leaves and its bactericidal effect in cotton cloth against E. Coli were studied
      in this work. Silver nanoparticles were synthesized by short-term (1 day) and
      long-term (21 days) interaction of Neem extract (20% w/v) and 0.01 M AgNO3
      solution in 1:4 mixing ratio. The synthesized particles were characterized by UV
      visible spectroscopy, transmission electron microscopy, and incorporated into
      cotton disks by (i) centrifuging the disks with liquid broth containing
      nanoparticles, (ii) in-situ coating process during synthesis, and (iii) coating
      with dried and purified nanoparticles. The antibacterial property of the
      nanoparticles coated cotton disks was studied by disk diffusion method. The
      effect of consecutive washing of the coated disks with distilled water on
      antibacterial property was also investigated. This work demonstrates the possible
      use of biologically synthesized silver nanoparticles by its incorporation in
      cloths leading them to sterilization.

PMID- 20055112
TI  - Methotrexate loaded self stabilized calcium phosphate nanoparticles: a novel
      inorganic carrier for intracellular drug delivery.
AB  - Calcium phosphate is considered as a potential biomaterial for drug and gene
      delivery because of its excellent features. In this study, we reported the
      formulation and characterization of calcium phosphate nanoparticle containing
      anticancer drug, methotrexate (MTX). Calcium phosphate nanoparticles containing
      MTX (CaPi-MTX) were prepared by reverse micelles technique. CaPi-MTX
      nanoparticles of average size 262 +/- 47.64 nm with entrapment efficiency of
      58.04 +/- 4.09% were obtained. The IR spectrum of CaPi-MTX showed characteristics
      of composite formation of hydroxyapatite with MTX. X-RD analysis revealed that,
      CaPi-MTX nanoparticles were crystalline and in hydroxyapatite form. TEM studies
      showed that CaPi-MTX nanoparticles were spherical in shape. In vitro release
      study of CaPi-MTX nanoparticles showed slow release of MTX at physiological pH
      (pH 7.4) while > 90% release was observed within 3-4 hours at endosomal pH (pH
      5.5 and pH 6.0). Confocal microscopy was performed using CHO cell lines, showed
      intracellular localization of FITC-Dextran loaded calcium phosphate
      nanoparticles. Results indicate that prepared CaPi-MTX nanoparticles could serve
      the purpose for intracellular drug delivery.

PMID- 20055113
TI  - Magnesium phosphate nanoparticles can be efficiently used in vitro and in vivo as
      non-viral vectors for targeted gene delivery.
AB  - Magnesium phosphate (MgPi) nanoparticles (NPs) encapsulating pSVbetagal and pEGFP
      have been used as novel non-viral vector for targeted gene delivery. These
      plasmid DNA loaded magnesium phosphate nanoparticles of diameter 100-130 nm were
      prepared in water-in-oil microemulsion. In vitro cell viability study carried out
      on MCF-7, HEK, and COS-7 cells demonstrated that magnesium phosphate
      nanoparticles have no cytotoxic effect against cell proliferation. In vivo
      cytotoxicity conducted on Swiss Albino mice indicated no cytotoxic effect 3
      months after intraperitoneal administration of 600 mg of void magnesium phosphate
      nanoparticles per Kg of body weight one-time only. In vitro transfection in COS-7
      cells demonstrated that magnesium phosphate nanoparticles showed approximately
      100% efficiency when compared to commercial transfecting reagent Polyfect as well
      as the transfection efficiency of calcium phosphate (CaPi) nanoparticles recently
      reported. Moreover, to explore the possibility of targeting these nanoparticles
      to specific tissue, we have surface modified these particles by adsorbing highlyt
      adhesive polymer, polyacrylic acid (PAA), followed by conjugating the carboxylic
      groups of the polymer with p-amino-thio-beta-galactopyranoside (PAG) using a
      cross-linking agent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and used
      these particles to target to liver in vivo successfully and more efficiently.

PMID- 20055114
TI  - Inherently colored antimicrobial fibers employing silver nanoparticles.
AB  - Here we are reporting a novel method of producing inherently colored
      antimicrobial fibers employing silver nanoparticles. Without using undesirable
      dyes and chemical finishes, colors as well as antimicrobial properties have been
      imparted in textile grade acrylic fibers through silver nanoparticles, in such a
      way that these properties become inherent part of the fibers. The motivation
      behind silver nanoparticles is their unique optical properties as well as
      biomedical applications. A composite solution of polyacrylonitrile copolymer
      containing silver nanoparticles, synthesized in-situ, was converted into fibers
      using solution spinning technique. The fibers, so formed, have in-built silver
      nanoparticles in size ranging from 20-120 nm. Colors ranging from red to blue
      could be prepared by varying the silver concentration, aggregate size and
      process. The antibacterial efficacy of the fiber was as high as 94.3% against
      Escherichia coli.

PMID- 20055115
TI  - Disinfection studies on TiO2 thin films prepared by a sol-gel method.
AB  - Transparent anatase TiO2 nanometer thin films were prepared by dip-coating on
      soda-lime glass plates via the sol-gel method. The un-calcined and the calcined
      films were characterized by X-ray diffraction (XRD), AFM, Nano-indentation
      (hardness and Young's modulus), UV-vis spectrometry, thickness and hydrophilicity
      (contact angle measurements). The photocatalytic activity of the thin films was
      evaluated by performing disinfection studies on the Gram-negative microorganisms
      like Escherichia coli, and Staphylococcus Aureus, a Gram-positive organism. The
      photocatalytic activity for both groups of organisms was studied in saline and
      nutrient broth. The leakage of potassium from the bacteria was observed parallel
      to cell viability. The activity of the sol-gel prepared TiO2 thin films were
      compared under UV lamps and natural day light (ND) lamps with Degussa P-25 TiO2
      thin films prepared on soda-lime glass using a polymer support and the commercial
      self-cleaning glass (SC). The sol-gel prepared thin films which were annealed at
      450 degrees C, show highest photocatalytic activity, the slowest conversion rate
      from hydrophilic to a hydrophobic state, light-induced hydrophilicity, and also
      higher disinfection activities compared to P-25 films and commercial self
      cleaning glass. The films also show excellent activities when continuously reused
      for more than a month.

PMID- 20055116
TI  - Sustained release from lipid-core nanocapsules by varying the core viscosity and
      the particle surface area.
AB  - Based on the structure of polymeric nanocapsules containing a lipid-dispersed
      core composed of caprylic/capric trygliceride (CCT) and sorbitan monostearate
      (SM), we hypothesized that varying the core component concentrations the drug
      release kinetic could be modulated. Our objective was also to determine the
      parameters which were responsible for controlling the drug release kinetics. The
      nanocapsules were prepared by interfacial deposition of poly(epsilon
      caprolactone). Interfacial hydrolysis of indomethacin ester (IndOEt) was used to
      simulate a sink condition of release. Mathematical modeling showed that the
      IndOEt half-lives increased (198 to 378 and 263 to 508 min) with the increase in
      the core lipid concentrations, and that the release mechanism was the anomalous
      transport. By increasing the SM concentration, the diameters were constant
      (around 250 nm) and the surface areas increased (from 1.06 x 10(4) to 1.51 x
      10(4) cm2 x ml(-1)), while by increasing the CCT concentration, the diameters
      increased (215 to 391 nm) and the surface areas reduced (1.46 x 10(4) to 1.06 x
      10(4) cm2 x ml(-1)). The presence of SM increased the viscosity of CCT and the
      IndOEt apparent permeability decreased from 4.26 x 10(-7) to 2.54 x 10(-7) cm x
      s(-1), while for CCT series, the apparent permeability was constant around 3.0 x
      10(-7) cm x s(-1). A mathematical correlation was established and the IndOEt
      apparent permeability can be estimated by the SM concentration. In conclusion,
      varying the CCT and SM concentrations the IndOEt release was controlled by the
      nanocapsule surface area and by the viscosity of the core, respectively.

PMID- 20055117
TI  - [Potential role of macrolides in the treatment of COPD: current evidence.
      (discussion)].

PMID- 20055119
TI  - [Antifungal susceptibility of Candida species isolated from patient with invasive
      fungal peritonitis and investigation on clinical breakpoints of itraconazole].
AB  - We investigated antifungal susceptibility of 96 Candida species strains (37
      strains of Candida albicans, 30 of Candida glabrata, 16 of Candida tropicalis and
      13 of Candida parapsilosis) isolated from patients with invasive fungal
      peritonitis. Antifungal activity showed micafungin (MCFG), voriconazole
      (VRCZ)>itraconazole (ITCZ)>fluconazole (FLCZ). Judged by clinical breakpoints of
      Clinical and Laboratory Standards Institute (CLSI), FLCZ-resistant C. albicans,
      ITCZ-resistant C. albicans and VRCZ-resistant C. albicans were detected in the
      frequency of 5.4% (2/37), 21.6% (8/37) and 5.4% (2/37), respectively. We also
      retrospectively investigated the association of both antifungal susceptibility
      judged by CLSI breakpoints and clinical efficacy in 16 patients with invasive
      fungal peritonitis treated by injectable ITCZ. Clinical success and failure were
      obtained in cases of ITCZ MIC < or = 1 microg/mL and > or = 4 microg/ml,
      respectively. We conclude that we should re-consider CLSI breakpoints on ITCZ.

PMID- 20055118
TI  - [Efficacy of tosufloxacin in genital chlamydial infections].
AB  - According to the 2006 and 2008 "Guidelines for diagnosis and treatment of
      sexually transmitted diseases" by the Japanese Society for Sexually Transmitted
      Diseases, quinolones, macrolides and tetracyclines are recommended to treat
      chlamydial infections. The administration method based on
      pharmacokinetic/pharmacodynamic theory, as well as the selection of antimicrobial
      drugs, is important in antimicrobial therapy. It is currently assumed that the
      efficacy of administering high-dose quinolones once a day is greater than
      dividing the dose over multiple administrations. To verify the treatment effects
      of the recommended tosufloxacin dose of 150 mg b.i.d. (300 mg/day) for 7 days, we
      performed a comparative multicenter open label study of 150 mg b.i.d. and 300 mg
      q.d. (300 mg/day). The results indicated complete efficacy with 100% (150 mg
      b.i.d.: 49/49, 300 mg q.d.: 57/57) eradication of Chlamydia trachomatis at both
      dosages. The clinical efficacy was "markedly effective" in 57.1% (28/49) of
      cases, "effective" in 42.9% (21/49), and "not effective" in 0% (0/49) in the 150
      mg b.i.d. group, while these values were 59.6% (34/57), 40.4% (23/57) and 0%
      (0/57), respectively, in the 300 mg q.d. group. Quinolone therapy for genital
      chlamydial infections with tosufloxacin doses of 150 mg b.i.d. was confirmed to
      be effective as recommended in the guidelines. Moreover, tosufloxacin at 300 mg
      q.d. was shown to be an effective therapy.

PMID- 20055120
TI  - Population pharmacokinetic modeling and pharmacodynamic assessment of cefozopran
      in pediatric patients.
AB  - The aims of this study were to develop a population pharmacokinetic model for
      cefozopran in pediatric patients, and to use this model to evaluate the
      pharmacodynamics of cefozopran regimens against common bacterial populations.
      Plasma drug concentration data (110 samples from 31 pediatric patients) were
      modeled using the NONMEM program. The mean estimate and interindividual variance
      of the model were used in a Monte Carlo simulation to estimate the probabilities
      of attaining the bactericidal target for cefozopran (the time which the drug
      concentration remains above the minimum inhibitory concentration for the
      bacterium is 70% of the dosing interval). A two-compartment model fitted the data
      and body weight (BW, kg) was the most significant covariate. The final model was:
      Cl (l/h) = 0.674 x BW0.538, Vc (l) = 0.00233 x BW2.25 + 1.85, Q (l/h) = 1.46, and
      Vp (l) = 0.0964 x BW, where Cl is the clearance, Vc, and Vp are the volumes of
      distribution of the central and peripheral compartments, and Q is the
      intercompartmental clearance. The approved regimens of 20- or 40-mg/kg four times
      a day (0.5-h infusions), which were more effective than the corresponding three
      times a day-regimens, provided sufficient bactericidal effects on common
      bacterial populations (Escherichia coli, Streptococcus pneumoniae, Haemophilus
      influenzae, and Pseudomonas aeruginosa) in most typical patients. These results
      better define the pharmacokinetics of cefozopran and help in the choice of
      appropriate regimens for pediatric patients.

PMID- 20055121
TI  - [Novel model of replicative Legionella pneumophila lung infection in DBA/2 mice].
AB  - We present here a new model of Legionella pneumophila lung infection in DBA/2
      mice. By intranasal inoculation with 106 colony-forming units of L. pneumophila
      strain suzuki serogoup 1, persistent non-lethal lung infection was established as
      reflected by the detection of more than 10(4) CFU/lung of the organism 14 days
      after infection. Treatment of mice with cyclophosphamide before infection
      enhanced bacterial replication in the lungs and all cyclophosphamide-treated mice
      experienced lethal infection. Histopathologically, the course of non-lethal lung
      infection was characterized by early response of neutrophiles, then
      monocyte/macrophages response in the alveoli with disease progression, and
      diffuse alveolar wall thickening with lymphocyte migration at later phase of
      infection. Transmission electron microscopic evaluation of the lungs confirmed
      that L. pneumophila located intracellularly within neutrophiles and infrequently
      intracellular bacteria were observed undergoing binary fission. Therefore, the
      mouse model of replicative L. pneumophila lung infection provides method for
      evaluating pathogenesis of L. pneumophila lung infection and antibacterial
      therapy.

PMID- 20055122
TI  - [Therapeutic efficacy of levofloxacin against a model of replicable Legionella
      pneumophila lung infection in DBA/2 mice].
AB  - The in vitro and in vivo antibacterial activities of levofloxacin (LVFX), a
      quinolone antibacterial, against clinically isolated Legionella pneumophila were
      investigated in comparison with those of existing antimicrobial agents approved
      for legionnaires disease. The minimum inhibitory concentrations (MICs) of the
      agents against 42 strains of L. pneumophila isolated in Japan were determined
      using agar dilution methods with buffered starch yeast extract agar. MIC90 of
      LVFX was 0.03 microg/ml and this activity was similar to ciprofloxacin and
      pazufloxacin, and higher than telithromycin and minocycline. Therapeutic efficacy
      of LVFX was studied against a pneumonia model induced by intranasal of L.
      pneumophila strain suzuki serogoup 1 in DBA/2 mice. Therapeutic doses in mice
      were selected that would closely match human exposure profile, area under the
      concentration-time curve (AUC) for a human oral dose of LVFX at 500 mg once a
      day. LVFX decreased significantly the bacterial burden in the lungs from the next
      day of commencing treatment. These results, including in vitro antibacterial
      activity against clinical isolates and therapeutic efficacy of a humanized dosing
      regimen, provide good evidence to support the use of LVFX at 500 mg once a day
      for treating patient with legionnaires disease.

PMID- 20055123
TI  - [Overseas Drug Safety Information 2008. Risk of infectious diseases associated
      with the use of immunosuppressive drugs].

PMID- 20055124
TI  - [Search for antitumor macrolides from marine dinoflagellates and their biomedical
      application].

PMID- 20055125
TI  - [Advances in the study of regulation of novel organic cation transporter-2].
AB  - Novel organic cation transporter-2 (OCTN2), a member of the organic cation
      transporter family, may transport carnitine and multiple organic cationic drugs.
      Thus OCTN2 possesses substantial roles in physiology and pharmacology. A number
      of researches have proven that many factors can regulate the expression and/or
      function of OCTN2 via different pathways, and then may affect the homeostasis and
      disposition of drugs. This paper reviews recent progresses in this field.

PMID- 20055126
TI  - [Bradykinin modulates ion channel in inflammatory pain].
AB  - Injury or inflammation induces release of a range of inflammatory mediators.
      Bradykinin is one of the most important inflammatory mediators and plays a
      crucial role in mediating inflammatory pain. It is well known that multiple ion
      channels located in the nociceptors participate in pain sensation. Recent studies
      demonstrate an important role of bradykinin in regulating the function and
      expression of pain-related ion channels. This paper summarizes the recent
      advances in the understanding of the role of bradykinin in modulation of the
      channels and discusses future possibilities in the treatment of inflammatory
      pain.

PMID- 20055127
TI  - [Structure-activity relationships of histone deacetylase inhibitors].
AB  - Among those enzymes that regulate gene expression, histone deacetylases (HDACs)
      play important roles in cell cycles. Extensive studies were carried out in the
      field of HDACs and the applications of HDAC inhibitors (HDACIs) as
      chemotherapeutic interventions for diverse diseases. HDACIs have moved from
      laboratories to clinic uses. Huge bodies of related research results were well
      documented and dispersed in literature. According to our understanding, HDACIs
      can be broadly classified as hydroxamic acids, cyclic tetrapeptides, short chain
      fatty acids, benzamides and electrophilic ketones. Herein, we are going to review
      the design and their structure-activity relationships of HDACIs and according to
      their structural catalogs.

PMID- 20055128
TI  - [Advances in the study of affinity selection-ultrafiltration/HPLC-MS].
AB  - Affinity selection-ultrafiltration/HPLC-MS is the combination of the
      ultrafiltration and HPLC-MS, mainly used for screening small active molecular
      substances from combinatorial libraries and natural product extracts, which can
      bind to solution-phase targets. Besides, it can be used in metabolic screening
      and characterization of ligand-receptor binding. It is a complement to the
      traditional methods of screening and identifying drugs. This review describes its
      principle and application in drug study.

PMID- 20055129
TI  - [Influence of rhBMP-2 on the renal tissue of rat with renal ischemia reperfusion
      injury and its molecular mechanism].
AB  - The objective of this research is to investigate the influence of rhBMP-2 on the
      renal tissue of rat with renal ischemia reperfusion injury. In this program the
      ischemia reperfusion rat model was established and Wistar rats were divided into
      six groups: sham operation group (S group), renal ischemia reperfusion injury
      group (R group), rhBMP-2 treatment group (B1, B2, B3 and B4 group). In the rhBMP
      treatment groups, rhBMP-2 was intravenously administered with different doses
      before reperfusion. The contents of TNF-alpha, IL-6, IL-8, MDA and SOD in kidney
      tissue were observed. At the same time, renal function (blood creatine (Scr) and
      urea nitrogen (BUN)) were measured. As a result, compared with renal ischemia
      reperfusion group, administration of rhBMP-2 significantly reduced the content of
      IL-6 and IL-8 (P < 0.05) and ameliorated renal dysfunction cellular damages (P <
      0.05). Higher dose of rhBMP-2 may reduce the content of TNF-alpha (P < 0.05) in
      kidney tissue. rhBMP-2 also increased activity of SOD and reduced the level of
      MDA, BUN and Scr. So, we can draw a conclusion that rhBMP-2 treatment attenuates
      renal ischemia reperfusion injury through inhibition of pro-inflammatory
      cytokines production and anti-oxidation activity.

PMID- 20055130
TI  - [Metabonomic profiling of plasma metabolites in Wistar rats to study the effect
      of aging by means of GC/TOFMS-based techniques].
AB  - The global metabolite profiles of endogenous compounds of Wistar rats from 12 to
      20 weeks old were investigated to take deep insight into and get better
      understanding of the pathogenesis of development and aging. Plasma from Wistar
      rats at 12, 14, 16, 18, and 20 weeks old were analyzed using GC/TOFMS.
      Multivariate data analysis was then used to process the metabonomic data which
      indicated excellent separation between different weeks and showed that the
      metabolic profiles of the samples changed with age, enabling age-related
      metabolic trajectories to be visualized. Decreased concentrations of citric acid,
      cis-aconitic acid, 9-(z)-hexadecenoic acid along with increased levels of
      hexanedioic acid, alpha-tocopherol, 3-indole propionic acid, etc contributed to
      the separation. Several major metabolic pathways were identified to be involved
      in metabolic regulation. This suggests that GC/TOFMS-based metabonomics is a
      powerful alternative approach to identifying potential biomarkers and
      investigating the physiological developments of aging and it is important to
      employ suitable age-match control group in metabonomic study of physiological
      monitoring, drug safety assessment, and disease diagnosis, etc.

PMID- 20055131
TI  - [Effect of p21-targeted shRNA on curcumin-induced apoptosis of human hepatoma
      Huh7 cells].
AB  - In the present study, shRNA plasmid of pSi-p21 targeting p21 mRNA was constructed
      and the effect of p21 shRNA on curcumin-induced apoptosis of human hepatoma Huh7
      cells was investigated. The effect of curcumin on the expression of p21 mRNA and
      protein and the silence efficiency of pSi-p21 were detected with RT-PCR and
      Western blotting. The effect of pSi-p21 on curcumin-induced apoptosis of Huh7
      cells was evaluated with DAPI staining. The results showed that curcumin
      significantly upregulated p21 mRNA and protein expression, which was knocked down
      by pSi-p21 of Huh7 cells. DAPI staining results showed that pSi-p21 significantly
      decreased curcumin-induced apoptosis of Huh7 cells. The data suggested that
      curcumin induced apoptosis of Huh7 cells via upregulation of p21 expression.

PMID- 20055132
TI  - [Inhibition effect of epalrestat on rat lens osmotic expansion].
AB  - Epalrestat is the unique aldose reductase inhibitor on the market, which was
      mainly used for the diabetic neuropathy. Lenses osmotic expansion could be
      induced by galactose to mimic the pathological process of diabetic cataract in
      vitro. In present study, we mainly investigated whether epalrestat possesses
      inhibitory effect on the lens osmotic expansion. The results indicated that
      epalrestat could not only markedly inhibit rat lens osmotic expansion in vitro,
      but also significantly reduced the high expression of the osmotic expansion
      related genes such as AR and AQP1 in mRNA and protein levels. The findings may
      provide an important reference to epalrestat in the clinical application for the
      treatment of diabetic cataract.

PMID- 20055133
TI  - [Synthesis and anti-histamine release activity of phenyl tetrazole compounds].
AB  - Ongoing effort to find novel antiasthmatic drugs led to the design and synthesis
      of a series of compounds bearing phenyl tetrazole group based on the SAR study.
      The important intermediate 3-(1H-tetrazol-5-yl) benzenamine was synthesized from
      m-nitroaniline via cyclization and hydrogenation. Followed by amidation, eight
      new target compounds were obtained. The structures of these compounds were
      confirmed with 1H NMR, ESI-MS and elemental analysis. Their non-specific and
      specific anti-histamine effects in the mast cell were determined. Compound NP03
      could inhibit non-specific histamine release induced by compound 48/80 in mast
      cell of SD rats.

PMID- 20055134
TI  - [Terpenoids from Euphorbia antiquorum L.].
AB  - To study the chemical constituents of Euphorbia antiquorum L., the constituents
      were isolated with normal-phase and reverse-phase silica gel column
      chromatography and their structures were elucidated on the basis of spectroscopic
      data. Seven terpenoids were obtained from EtOAc extract of E. antiquoru L. They
      were identified as antiquorine A (1), antiquorine B (2), ent-13S-hydroxy-16
      atisene-3,14-dione (3), taraxerol (4), 3beta-hydroxy-25,26,27-trisnorcycloart-24
      oic acid (5), 9beta,19-cyclolanostan-3beta-ol (6) and psi-taraxastane-3,20-diol
      (7) by spectral analysis. Compounds 1-3 are diterpenoids, which belonged to
      abietane, ent-kaurane and atisane respectively. Among them, compounds 1 and 2 are
      new compounds. Compounds 4-7 are triterpenoids, and compound 5 is a degraded
      cycloartane triterpenoid which is a new natural product. Compound 7 was isolated
      from this plant for the first time. It demonstrated that the chemical structures
      of constituents in this plant were diverse.

PMID- 20055135
TI  - [A new trincallane derivative from Salacia hainanensis Chun et How].
AB  - Chemical constituents of the roots and stem of Salacia hainanensis Chun et How
      were isolated and purified with column chromatography on silica gel, Sephadex LH
      20 and preparative HPLC. Their structures were elucidated based on
      physicochemical and spectral spectroscopic analysis. Depending on the activities
      of anti-alpha-glucosidase and inhibiting AGEs (advanced glycation end products,
      AGEs) formation in vitro, nine compounds were identified as 26, 27-dihydroxy-7,
      24-tirucalladien-3-one (1), abruslactone A (2), lupeol (3), 21alpha, 30-dihydroxy
      D: A-friedooleanan-3-one (4), 15alpha-hydroxyfriedelan-3-one (5), friedelin (6),
      mangiferin (7), epicatechin (8) and beta-sitosterol (9), separately. Among them,
      compound 1 is a new compound, and compound 2 was isolated from the Salacia genus
      for the first time, while, compounds 3, 4, 5, 8 were obtained from this plant for
      the first time.

PMID- 20055136
TI  - [Microcalorimetric investigation of two cephalosporins on colon bacteria
      activity].
AB  - The effects of cephradinum and ceftazidime on the metabolism of Escherichia coli
      (E. coli) DH5alpha was determined by microcalorimetry. The microbial activity was
      recorded as power-time curves through an ampoule method with a TAM Air Isothermal
      Microcalorimeter at 37 degrees C. The parameters such as the growth rate constant
      (k), inhibitory ratio (I), the maximum power output (Pm) and the time (tm)
      corresponding to the maximum power output were calculated. The results show that
      the ceftazidime has a better inhibitory effect on E. coli DH5alpha than
      cephradinum.

PMID- 20055137
TI  - [Metabolism of osthol in isolated hepatocytes of rat].
AB  - The paper is aimed to study the metabolic characteristics of osthol (Ost) in
      isolated hepatocytes of rat to identify which isoforms of CYP450 were responsible
      for Ost metabolism in vitro. The concentration of Ost in isolated hepatocytes
      incubation system was determined by HPLC-UV. The effects of incubation time,
      substrate concentration and hepatocytes amount on the metabolic characteristics
      of Ost were investigated. CYP2C8 inhibitor quercetin (Que), CYP2C9 inhibitor
      sulfaphenazole (Sul), CYP2D6 inhibitor yohimbine (Yoh), CYP3A4 inhibitor
      troleandomycin (Tro) and CYP450 inducer rifampicin (Rif) were used to investigate
      their effects on the metabolism of Ost. The metabolism of Ost in isolated rat
      hepatocytes showed an enzymatic kinetic characteristics. Rif induced Ost
      elimination in rat hepatocytes; Yoh, Sul, Que did not have effects on Ost
      metabolism in vitro. Between 0-200 micromol x L(-1), Tro inhibited Ost metabolism
      in a concentration-dependent manner. CYP3A4 is the enzyme metabolizing Ost in
      vitro; CYP2C8, CYP2C9 and CYP2D6 did not involve in Ost metabolism in rat
      hepatocytes.

PMID- 20055138
TI  - [Determination of colistin based on biothermal activity detection method].
AB  - A biothermal activity detection method has been established to determine the
      potency of colistin. The biothermal activity fingerprints of E. coli with
      colistin were determined. There was a good linear relationship (r = 0.993)
      between logarithm concentration of colistin (lgC) and lag rate of growing time
      (Deltat%) when the concentrations of colistin ranged from 17.0 to 41.6 u x mL(
      1). The average recovery rate was 100.3% (n = 9). Using this method, there was no
      significant difference between results of colistin potency measurement and those
      using cup-plate method (P > 0.05). As a result, biothermal activity detection
      method is sensitive, accurate, rapid, convenient and feasible to determine the
      potency of colistin. This method can also be applied in real time and online to
      monitor the process of bacterial growth and could be complementary to the cup
      plate method.

PMID- 20055139
TI  - [Determination of icaritin in rat plasma by HPLC-MS/MS].
AB  - The paper is to report the development of a high-performance liquid
      chromatographic/tandem mass spectrometry (HPLC-MS/MS) method for the
      determination of icaritin (ICT) in rat plasma. After precipitated with
      acetonitrile from the plasma, ICT was isolated chromatographically on a Dikma C18
      column. The mobile phase consisted of acetonitrile-water-acetic acid (72 : 28 :
      1.5, v/v/v). Electrospray ionization (ESI) source was applied and operated in the
      positive ion mode. Multiple reaction monitoring (MRM) mode with the transitions
      of m/z 387 --> m/z 313 and m/z 331 --> m/z 315 were used to quantify ICT and the
      internal standard, respectively. The linear calibration curve was obtained in the
      concentration range of 2.5-1,000 ng x mL(-1). The lower limit of quantification
      was 2.5 ng x mL(-1). The inter- and intra-day precision (RSD) were less than
      9.63%, and the accuracy (relative error) was within +/-7.42%. The method was
      proved to be suitable for the pharmacokinetics of ICT, which offers advantages of
      high sensitivity and selectivity.

PMID- 20055140
TI  - [Population pharmacokinetic study of tacrolimus in patients with hematopoietic
      stem cell transplant].
AB  - The present study is to establish the population pharmacokinetic (PPK) model of
      tacrolimus and to estimate PPK parameters of tacrolimus for the individualization
      of tacrolimus administration in patients with hematopoietic stem cell transplant.
      A total of 671 blood samples were collected from 68 hematopoietic stem cell
      transplant patients and clinical data were retrospectively collected from the
      medical records of these patients. Population pharmacokinetical analysis was
      performed using the nonlinear mixed-effect model (NONMEM) program. The Bootstrap
      and data splitting were used simultaneously to validate the final population
      pharmacokinetical models. The basic structural model was best described as one
      compartment pharmacokinetical model with first-order absorption and elimination.
      A number of covariates including demographic characteristic, biochemical and
      hematological index, combined drugs, inter-occasion variability (IOV) and other
      variables, e.g. primary disease, post operation days (POD), the type of
      transplantation and the sources of donor, were screened for their influence on
      the pharmacokinetic parameters of tacrolimus. The population typical values of
      tacrolimus CL, V, F were 12.1 L x h(-1), 686 L, 42.2%; and the inter-individual
      variability of these parameters were 23.5%, 96.4%, 43.8%, respectively. The
      absorption rate constant was fixed 4.3 h(-1). The residual error between observed
      and model- predicted concentration was 3.03 ng x mL(-1). The CYP enzyme inhibitor
      (INHI), POD and age were identified to be the main covariates that influence
      tacrolimus CL, and hemoglobulin (HGB) was the main covariate that may explain the
      variability in tacrolimus V. The IOV of CL, V, F were 22.2%, 6.23%, 30.3%,
      respectively. The population pharmacokinetic data obtained in the present study
      have significant clinical value for the individualization of tacrolimus therapy
      in hematopoietic stem cell transplant patients.

PMID- 20055141
TI  - Preparation and evaluation of colon targeted drug delivery systems for
      albendazole using kneading, extrusion and compaction technology.
AB  - Albendazole is an orally administered broad-spectrum benzimidazole anthelmintic
      used against helminthiasis, hydatid cyst disease and neurocysticercosis. The
      objectives of this investigation are to develop a sustained release drug delivery
      system for albendazole, and to target its delivery to colon. Albendazole matrix
      tablets containing varying proportions of single and binary blends of four
      polymers; polyacrylic acid (carbopol 971), ethylcellulose (Etcell), eudragit L100
      55 (EUD), and sodium carboxymethyl cellulose (CMC) were prepared by a modified
      wet granulation technique of kneading, extrusion and compaction. In vitro release
      profiles of albendazole was sequentially determined in simulated gastric fluid
      (SGF), simulated intestinal fluid (SIF) without enzymes and in rat caecal content
      medium (RCCM) at 37 degrees C. The in vitro drug release from matrix tablets
      containing CMC and Etcell as single polymers showed initial burst effect in the
      first 2 h (>20% and 50% respectively), followed by a slow release in SIF.
      However, matrix tablets containing polymer blends showed that no appreciable drug
      release occurred up to 5 h. Drug release from tablets containing polymer blends
      in the dissolution medium containing rat caecal material suddenly increased to >
      or =30% after 5 h (RCCM), and reaching up to 90% in 24 h. Albendazole matrix
      tablets containing carbopol 971, Etcell, EUD, and CMC as single polymers and as
      blends were formulated for oral use. Drug release from the tablet matrices
      containing carbopol alone, binary blends of carbopol/Etcell, and CMC/EUD were
      found to be very slow and dependent on polymer concentration. Matrix tablets
      containing blends of these polymers formulated using kneading, extrusion and
      compaction technique could provide sustained drug release and can be utilized in
      the colonic delivery of albendazole.

PMID- 20055142
TI  - [Artificial neural network parameters optimization software and its application
      in the design of sustained release tablets].
AB  - Artificial neural network (ANN) is a multi-objective optimization method that
      needs mathematic and statistic knowledge which restricts its application in the
      pharmaceutical research area. An artificial neural network parameters
      optimization software (ANNPOS) programmed by the Visual Basic language was
      developed to overcome this shortcoming. In the design of a sustained release
      formulation, the suitable parameters of ANN were estimated by the ANNPOS. And
      then the Matlab 5.0 Neural Network Toolbox was used to determine the optimal
      formulation. It showed that the ANNPOS reduced the complexity and difficulty in
      the ANN's application.

PMID- 20055143
TI  - [Identification, characterization and utilization of simple sequence repeat
      markers derived from Salvia miltiorrhiza expressed sequence tags].
AB  - Despite Salvia miltiorrhiza being one of the most important medicine plants in
      China, there is a limited availability of genomic resources, especially of the
      expressed sequence tag-based markers. In this study, we selected and
      characterized functional markers in S. miltiorrhiza, which consisted of 4,192 non
      redundant expressed sequence tags (ESTs) from 10,288 identified S. miltiorrhiza
      ESTs in dbEST data bank. Among them, 159 simple sequence repeats (SSR) were
      detected, which amounted to 3.79% of the non-redundant starting sequence
      population. This incidence was equivalent to one EST-SSR in every 12.74 kb of S.
      miltiorrhiza ESTs. Among the different motifs ranging from 1 bp to 6 bp, di
      nucleotide repeat motif was the most abundant (77, 48.43%), followed by tri
      nucleotide (41, 25.79%), hexa-nucleotide (23, 14.47%), penta-nucleotide (12,
      7.55%) and tetra-nucleotide (6, 3.77%). In 47 identified motif types, the
      detected frequency above 5% were GA/CT (16.35%), AG/TC (15.09%), TCA/AGT
      (10.69%), AT/TA (6.29%), GAAAAG/CAAAAC (6.29%) and TA/AT (5.03%). Based on flank
      sequence of detected SSR, a total of 83 EST-SSR primer pairs were designed and
      tested for the amplification efficiency, polymorphism and transferability in
      thirteen S. mihiorrhiza samples and other ten species from the genus Salvia. The
      results showed that 72 primer pairs were successfully amplified in S.
      miltiorrhiza samples to yield and 279 loci with an average of 3.88 loci per
      primer pair. The cross-transferability of S. miltiorrhiza EST-SSR markers to
      other ten Salvia plants was very high, ranging from 60% to 100% with an average
      of 85%. Further analysis of the genetic similarity based on the polymorphic bands
      showed the EST-SSR could detect the genetic diversity on different levels among
      the whole test samples and distinguish the S. miltiorrhiza from other Salvia
      plants effectively. It is expected that the potential markers described here
      would add to the repertoire of DNA markers needed for genetic analysis, linkage
      mapping and comparative genomics studies in S. miltiorrhiza and related Salvia
      genus plants.

PMID- 20055144
TI  - [Analysis and authentication of cpDNA psbA-trnH regions of Dendrobium species of
      fengdous].
AB  - The psbA-trnH regions of Dendrobium species of Fengdous were sequenced by our
      research group. The psbA-trnH sequences of fifteen Dendrobium species were
      analyzed with software MEGA 4.0. The results showed that the lengths of sequences
      varied from 721 to 767 bp. The variable sites were 42 while the informative sites
      were 11. Genetic distances were calculated using the Kimura 2-parameter model.
      Genetic distances varied from 0.0013-0.0183 among fifteen species while the
      average genetic distance was 0.0148. The interspecies differences of psbA-trnH
      regions were demonstrated. Six indels happened in this fragment, which led to the
      great difference of sequence lengths among fifteen species. We found that there
      were no population differences in the psbA-trnH region of various species of
      Fengdous so far. By using the database of various Dendrobium species of Fengdous
      and two genetics software, the botanical origin of the inspected species of
      Fengdous was authenticated successfully by sequencing the psbA-trnH regions. The
      psbA-trnH region of cpDNA can be used as a candidate marker for authentication of
      Dendrobium species of Fengdous.

PMID- 20055145
TI  - [The improvement of poorly water-soluble drug solubility through electrospun drug
      loaded nanofibers].
AB  - The improving effect of electrospun drug-loaded nanofibers on the solubility of
      poorly water-soluble drug was investigated in the present research. Drug-loaded
      nanofibers were successfully prepared using electrospinning process with helicid
      as the poorly water-soluble model drug and polyvinylpyrrolidone K60 (PVP K60) as
      the filament-forming matrix. Scanning electron microscopy observation
      demonstrated that the nanofibers had a three-dimensional continuous web
      structure, and had well smooth surface and a diameter between 400-600 nm. X-ray
      diffraction results suggested that helicid lost its original crystal structure
      but highly distributed into the nanofibers in an amorphous state, resulting from
      the hydrogen bonding interactions between the carboxylic group of PVP K60 and the
      hydroxyl groups of helicid. The drug-loaded nanofibers obviously improved
      helicid's solubility, and were able to completely release the whole drug in 60 s.
      Electrospun drug-loaded nanofibers can improve the solubility and release
      profiles of poorly water-soluble drug.

PMID- 20055146
TI  - [Determination of the components of bitespiramycin by HPLC].
AB  - The paper is to report the establishment of an HPLC method for determination of
      the components of bitespiramycin and its products, and to evaluate the components
      profile of bitespiramycin and its related products. Liquid chromatography
      combined with mass spectrometry (LC-MS) was used to identify the nine major
      components of the reference substance of bitespiramycins. The nine components of
      bitespiramycins and its products have been quantified by HPLC with gradients
      elution methods. The content of the component of 4"-O-isovalerylspiramycin III
      was not less than 35%, the content of the components of 4"-O-isovalerylspiramycin
      (I + II + III) was not less than 60%, and the contents of the nine components of
      bitespiramycin were not less than 80%, separately. In addition to the components
      mentioned above, there also exists some other impurities, however, with lower
      contents. This gradient elution HPLC method reported by this paper is considered
      to be suitable for the quality control of bitespiramycin.

PMID- 20055147
TI  - [The role of vitagene in aging and Alzheimer's disease and relevant advances of
      pharmacological study].
AB  - Free radical hypothesis of aging emphasized that the age-related accumulation of
      free radicals results in cell injury. Alzheimer's disease (AD) is the most common
      form of neurodegenerative disease characterized by impaired cognition and memory
      of the elderly. Aging is a key risk factor in AD. Substantial evidence suggests
      that imbalance between free radical formation and clearance promotes AD
      pathogenesis. The brain overcomes oxidative stress by inducing expression of a
      set of genes called vitagenes. The protein products of vitagenes include heat
      shock proteins, heme oxygenases and thioredoxin systems, which serve as
      endogenous lifeguard of cells. This paper is a review of the expression and
      function of vitagenes in aging and AD brain, as well as relevant pharmacological
      study.

PMID- 20055148
TI  - [A novel target for the regulation of cardiac arrhythmias--microRNAs].
AB  - microRNAs are one kind of endogenous no-encoding RNA with about 22 nucleotides in
      length, and inhibited the translation of mRNAs by partially complementary binding
      to the 3' UTR of target mRNAs in the post-transcriptional level. Recent research
      shows that miRNAs function in the physiological and pathological processes of
      heart, especially involved in the occurrence and progress of arrhythmias.
      Abnormal miRNAs alters the protein expression of ion channels, causes the cardiac
      dysfunction, and triggers heart arrhythmias. The article summarized recent
      advances about roles of miRNA in arrhythmias and related cardiomyopathy, and
      discussed the therapeutic potential of miRNAs for heart diseases.

PMID- 20055149
TI  - [Advances in the study of organelles targeting nanocarriers].
AB  - Modern drug delivery system demands high therapeutic efficacy and low toxicity
      which depends on efficient intracellular transportation of therapeutics to
      specific organisms, cells, even targeted organelles such as cytosol, nucleus,
      mitochondria, lysosome and endoplasmic reticulum. Intracellular barriers which
      prevent drug molecules accessing to their targets mainly include cell membrane,
      lysosomal degradation and the endomembrane system. Nanocarriers can preserve the
      bioactivities of protein, enzyme and DNA, and also they are easy to be modified
      and functionalized. In this paper, we summarized the intracellular fate of
      nanocarriers, especially how to bypass intracellular barriers and then target
      cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum by
      pharmaceutical modifications.

PMID- 20055150
TI  - [Progress in the development of crystallized proteins as drug delivery system].
AB  - Crystallization has been widely applied in pharmaceutical formulations as an
      effective approach to improve the stability and efficacy of small agents. However
      protein crystals are suffered from limitation in the drug delivery system due to
      their complex crystallization behaviors. With development of crystallization
      technologies and their industrial application, protein crystals are receiving
      more and more attentions as a novel delivery system for biomacromolecules.
      Crystals with thermodynamic stable structure can improve the physical and
      chemical stability of protein drugs and present a sustained release behavior. On
      the basis of pertinent literatures, this review introduces the recent research
      situation and development process of protein crystals as drug delivery system.
      Moreover, the crystallization process of proteins, as well as the preparation and
      potential application are discussed systematically.

PMID- 20055151
TI  - [Allergic response to qingkailing injection in BN rats].
AB  - This study is to observe allergic response to Qingkailing injection in BN rats
      and to establish a suitable animal model to evaluate allergic response induced by
      traditional Chinese medicine. BN rats were sensitized by Qingkailing injection,
      and guinea pigs were similarly sensitized as the control. The symptoms of
      allergic response were observed, the levels of histamine in serum and tissues
      were determined by ELISA assay and pathological changes in lung and trachea were
      observed with HE staining under light microscope. The total incidence of allergic
      response in BN rats was 52.78%, which was higher than that in guinea pig groups
      (16.67%). The total degree of allergic response in BN rats was higher than that
      in guinea pigs. Compared with control groups, the level of histamine in serum,
      lung and trachea tissues of BN rats and guinea pigs increased significantly. The
      release rate of histamine in BN rats was higher than that in guinea pigs. The
      rate and degree of pathological changes in lung and trachea tissues of BN rats
      were higher than that in guinea pigs. Compared with guinea pig, BN rat is
      probably a suitable animal model in evaluating allergic response to injection of
      traditional Chinese medicine.

PMID- 20055152
TI  - [Comparison of the action of isolichenin and methanol extract of saffron on long
      term potentiation in hippocampal dentate gyrus in vivo].
AB  - Long-term potentiation (LTP) is thought as a generative mechanism underlying
      learning and memory via storing information in central nervous system. Electro
      neurophysiological assay for LTP is generally used in screening the drugs that
      can facilitate learning and memory. By using in vivo LTP technique, isolichenin
      was found to facilitate LTP induction by a tetanic stimulation (20 pulses/100 Hz)
      in dentate gyrus. This tetanic stimulation by itself, however, cannot induce LTP.
      Previous study showed the reagent being able to facilitate LTP-induction, like
      methanol extract of saffron (MES), usually can antagonize the inhibiting effect
      of 30% ethanol on LTP induction (30 pulses/60 Hz). Isolichenin may also fall into
      such kind of drugs. Interestingly, comparatively study showed that isolichenin
      failed to antagonize the inhibiting effect of 30% ethanol on LTP induction (30
      pulses/60 Hz). This result indicates a different unknown mechanism existing in
      the effect of isolichenin on LTP or memory formation.

PMID- 20055153
TI  - [Effects of extracts of cheezheng pain relieving plaster on nitric oxide and iNOS
      expression in macrophages induced by lipopolysaccharides].
AB  - This study is to explore the effects of extracts of Cheezheng pain relieving
      plaster (ECPRP) on nitric oxide (NO) production and expression of inducible
      nitric oxide synthase (iNOS) in macrophages induced by LPS and the mechanism
      involved. Nitric oxide level was measured with Griess reagent assay. Inducible
      nitric oxide synthase (iNOS) protein and NF-kappaBp65 fragment were detected with
      Western blotting. ECPRP (62.5 and 125 mgL(-1)) significantly inhibited the
      increase of nitric oxide level. Furthermore, ECPRP (62.5 and 125 mg x L(-1))
      notably reduced the expression of iNOS mRNA and protein. ECPRP (62.5 and 125 mg x
      L(-1)) elevated the content of I-kappaB protein in cytoplasm, while decreased the
      content of NF-kappaBp65 protein in nucleus. These results suggest that ECPRP
      reduce nitric oxide level via down-regulation of NF-kappaB-iNOS-nitric oxide
      pathway, resulting in prevention of inflammation.

PMID- 20055154
TI  - [Preparation and spectral characterization of apigenin molecularly imprinted
      polymer].
AB  - An apigenin molecularly imprinted polymer was prepared by bulk polymerization
      using apigenin as template, acrylamide (AA) as a functional monomer, ethylene
      glycol dimethacrylate (EDMA) as a crosslinking agent, acetonitrile and N, N
      dimethylformamide as porogenic solvents, and 2, 2'-azobisisobutyronitrile (AIBN)
      as an initiator. The interaction between template and functional monomer was
      proved by ultraviolet visible (UV) spectrophotometry and based on the results,
      appropriate reaction solvent was selected and the synthesizing process was
      estimated. The molecularly imprinted polymer structure was analyzed by Fourier
      Transform Infrared (FT-IR) spectrophotometry. The molecularly imprinted polymer
      was investigated in equilibrium binding experiment to evaluate its adsorption
      property, the results showed that the adsorption of apigenin on molecularly
      imprinted polymer is higher than that on blank polymer in the studied
      concentration range (0.1-2.5 mmol x L(-1)). Scatchard analysis showed that two
      classes of binding sites existed in the apigenin imprinted polymers, with their
      KD and Qmax estimated to be 2.52 x 10(-4), 0.54 x 10(-3) mmol x L(-1) and 2.65,
      18.89 micromol x g(-1), respectively. Molecularly imprinted polymer showed higher
      affinity than blank polymer.

PMID- 20055155
TI  - [Synthesis of biflavones and their interaction with DNA].
AB  - To explore new biflavones, 7-hydroxy-8-hydroxymethyl-4'-methoxyisoflavone (1),
      (5, 7-dihydroxyflavone-8-yl)-(7'-hydroxy-4"-methoxyisoflavone-8'-yl)methane (2),
      bis(7-hydroxy-4'-methoxyflavone-8-yl) methane (3), bis(3', 5'-diisopropyl-7, 4'
      dihydroxy-isoflavone-8-yl)methane (4), and bis(7-hydroxy-isoflavone-8-yl) methane
      (5) were designed and synthesized from chrysin, formononetin, 7, 4'-dihydroxy-3',
      5'-diisopropyl-isoflavone and 7-hydroxy-isoflavone. Their structures were
      identified with IR, 1H NMR, 13C NMR and elemental analysis. The binding of 1-5
      with DNA was studied with fluorescent spectroscopy. Compounds 2-5 showed higher
      binding affinity with DNA than 1. According to the Stern-Volmer equation, the
      binding constants of 2, 3 were determined at 35 degrees C and 25 degrees C
      respectively, they were Kq2 (25 degrees C) = 1.95 x 10(4) Lx mol(-1) and Kq2 (35
      degrees C) = 1.67 x 10(4) L x mol(-1); Kq3 (25 degrees C) = 1.89 x 10(4) L x mol(
      1) and Kq3 (35 degrees C) = 1.58 x 10(4) L x mol(-1). The quenching mechanism of
      2, 3 was suggested as static quenching.

PMID- 20055156
TI  - [Synthesis and biological evaluation of 3-quinolinecarbonitrile-7-amide
      derivatives].
AB  - A series of N-(3-cyano-6-methyl-4-anilinoquinoline-7-yl) amide derivatives 13a
      13n have been synthesized, their structures were confirmed with 1H NMR, EI-MS, IR
      and elemental analysis. Antitumor activities of all the synthesized compounds in
      vitro were tested with MTT. Compound 13j showed better than or equal antitumor
      activity on Bosutinib and EKB-569.

PMID- 20055157
TI  - [Effect of processing on the chemical contents and hepatic and renal toxicity of
      rhubarb studied by canonical correlation analysis].
AB  - In this article, canonical correlation analysis was used to explore the
      relationship between the toxicity-attenuating effect and the variation of
      chemical contents in rhubarb caused by processing. With quasi-acute toxicity
      test, the difference of hepatic and renal toxicity to mice with the processed
      materials of rhubarb was researched. The chemical contents of anthraquinones and
      tannins in rhubarb were measured by UV-vis spectrophotometry and high performance
      liquid chromatography. The results showed that there were toxic effects to liver
      and kidney in mice after repeated intragastric administration of rhubarb and its
      processed materials for 14 days at a dosage of 76 g x kg(-1). The toxic effect of
      processed materials was much lower than crude drug. With canonical correlation
      analysis, the sequence of the hepatic and renal toxicity of chemical contents in
      rhubarb were found as follows: total anthraquinone glycosides (AQGs) > tannins
      (Tns) > total anthraquinones (AQs); aloe-emodin (AE) > physcione (Ph) > rhein
      (Rn) > emodin (Ed) > chrysophanol (Ch) and AEG > PhG > ChG > EdG > RnG of
      glycosyl-anthraquinone. It could be concluded that processing would attenuate the
      toxicity of crude drug of rhubarb. The toxicity-attenuating effect might be
      correlated to the decline of the contents of both anthraquinone glycosides and
      tannins, especially the aloe-emodin glycoside and physcione glycoside. The
      results also suggested that the serum alanine aminotransferase (ALT) and creatine
      (CREA) would be useful to monitor the hepatic and renal toxicity of rhubarb.

PMID- 20055158
TI  - Triterpenoid from Lycopodium obscurum L.
AB  - To study the triterpenoid constituents from air-dried whole plants of Lycopodium
      obscurum L., the constituents were isolated by normal-phase and reverse-phase
      silica gel column chromatography from the EtOAc extract. Their structures were
      elucidated on the basis of spectral analysis. Five triterpenoids were purified
      and identified as 3beta, 19alpha-dihydroxy-20beta-acetate-serrat-14-en-21beta-ol
      (1), serratenediol (2), alpha-onocerin (3), 26-nor-8-oxo-alpha-onocerin (4),
      (3beta, 8beta, 14alpha, 21alpha)-26, 27-dinoronocerane-3, 8, 14, 21-tetrol (5).
      Compound 1 is a new serratane-type triterpene and compound 5 is isolated from
      this plant for the first time.

PMID- 20055159
TI  - Investigation on the chemical constituents and variation of the flower buds of
      Lonicera species by UPLC-ESI-MS/MS and principle component analysis.
AB  - A rapid ultra-performance liquid chromatography-electrospray ionization tandem
      mass spectrometric (UPLC-ESI-MS/MS) method is developed for the qualitative
      identification of constituents in the flower buds of seven Lonicera species. The
      optimal condition of separation and detection were achieved on an AcQuity UPLC
      BEH C18 column with a gradient elution with acetonitrile and 0.1% acetic acid
      within 17 min. Among the 33 constituents detected, 6 caffeoylquinic acids
      (including caffeic acid), 8 flavonoids and 8 iridoid glycosides were
      characterized based on their fragmentation patterns in collision-induced
      dissociation (CID) experiments and/or by comparison with standard compounds. In
      addition, to statistically establish the correlation and discrimination of the
      Lonicera species, principle component analysis (PCA) was applied in this study.
      Lonicera samples were divided into well-defined groups directly related to their
      species based on PCA in terms of the log transformed relative contents of the
      major caffeoylquinic acids (including caffeic acid) as the variables. All of
      results indicated that the method presented here is able to classify the sample
      species and to reveal characteristic details of the chemical constituents of
      different Lonicera species.

PMID- 20055160
TI  - [Investigation on the chiral recognition site of enantioselective separation of
      ofloxacin by capillary zone electrophoresis using vancomycin as a chiral
      selector].
AB  - The chiral recognition site of the macrocyclic antibiotic vancomycin, used as a
      chiral selector in capillary electrophoresis (CE), was studied with ofloxacin,
      antofloxacin (a new fluoroquinolone antibiotic under development) and R
      antofloxacin, as well as with norvancomycin. Enantioselectivity of vancomycin and
      norvancomycin was compared. The influence of vancomycin concentration, pH of
      buffer, and separation voltage in CE were examined in order to investigate
      interactions between enantiomers and vancomycin. Furthermore, interactions of
      chiral selectors and enantiomers were calculated by molecular mechanics method
      with Chem 3D software. The result indicates that both vancomycin and
      norvancomycin have two domains in 3D structure, and the domain I of vancomycin
      was considered to be the chiral recognition site of ofloxacin. The degree of
      interaction between vancomycin and ofloxacin is determined as follows: hydrogen
      bond occurring with carboxylic group at C-6 of ofloxacin and hydroxyl group of
      sugar part of vancomycin, the matching degree of molecular sizes of ofloxacin
      with the pocket in domain I of vancomycin and the hydrophobic interaction between
      methyl group at C-10 of piperidine group of ofloxacin and N-methyl leucine of
      vancomycin.

PMID- 20055161
TI  - [Paclitaxel carried by long circulating microemulsions used for metabonomic
      chemotherapy of cancer].
AB  - Long circulating paclitaxel microemulsions (TXL-M) were prepared and its
      anticancer effect was evaluated in metronomic chemotherapy of cancer using animal
      tumor models. In TXL-M, paclitaxel was dissolved in vitamin E and polyethylene
      glycol-distearoylphosphatidylethanolamine (PEG-DSPE) was used as surfactant. The
      shape and particle size distribution of TXL-M were evaluated using an electronic
      microscope and a laser size scanner. The toxicity comparisons of TXL-M and
      paclitaxel were conducted using mice. Its anticancer effect and long circulation
      were evaluated using animal tumor model in C57BL/6 mice. The average diameter of
      TXL-M was (98.6 +/- 11.2) nm and its zeta potential was (-32.4 +/- 6.8) mV.
      Compared with paclitaxel, TXL-M showed lower toxicity. When used in metronomic
      chemotherapy of cancer, TXL-M showed longer circulation time in the blood and
      greater anticancer effect than paclitaxel. Thus, TXL-M is a better candidate for
      metronomic chemotherapy of cancer than paclitaxel injection.

PMID- 20055162
TI  - [The enhancing effect of borneol on the absorption of tetramethylpyrazine].
AB  - To explore the mechanism of the absorption enhancement of borneol, the effect of
      borneol on the intestinal absorption and the pharmacokinetics of
      tetramethylpyrazine phosphate after oral administration were investigated. In
      situ intestinal recirculation was performed to study the effect of various
      concentrations of borneol on the absorption of tetramethylpyrazine phosphate at
      duodenum, jejunum, ileum and colon. After oral administration of
      tetramethylpyrazine phosphate, the mixture of tetramethylpyrazine phosphate and
      borneol and the mixture of tetramethylpyrazine phosphate and verapamil in rats,
      the concentrations of tetramethylpyrazine phosphate in plasma were determined by
      RP-HPLC at predesigned time. The pharmacokinetic parameters were compared based
      on the results of the three animal experiments, and analyzed with software
      program 3p97. The result showed that tetramethylpyrazine phosphate could be
      absorbed at all of the four intestinal segments with increasing absorption amount
      per unit as follows: colon > duodenum > jejunum > ileum, but without saturation,
      which demonstrated that tetramethylpyrazine phosphate was absorbed via simple
      diffusion. Borneol could enhance the intestinal absorption of tetramethylpyrazine
      phosphate, however, not in proportion. There was no obvious difference between
      the test group and the control group when 10 microg x mL(-1) borneol was added (P
      > 0.05), while when the concentration comes to 25 microg x mL(-1) and 50 microg x
      mL(-1), significant differences were observed (P < 0.05). Borneol and verapamil
      did enhance the bioavailability of tetramethylpyrazine phosphate after oral
      administration in rats. The enhancing effect of borneol showed only when the
      concentration came to a certain level but with no specific sites existed in the
      intestine. One of the mechanisms of borneol on the enhancing effect on absorption
      of tetramethylpyrazine phosphate might be the inhibition of the metabolism of CYP
      3A and exocytosis of P-gp.

PMID- 20055163
TI  - [Intestinal absorption of daphnetin by rats single pass perfusion in situ].
AB  - This study investigated the effects of concentration, intestinal section, pH and
      P-gp on the absorption of daphnetin. The absorptions of three concentrations (10,
      20, 40 microg x mL(-1)) of daphnetin in different intestinal segments were
      studied with phenol red as the marker by in situ rats single pass perfusion
      model. The results showed that daphnetin was stable under pH 6.0 condition and
      little affected by metabolism enzyme. There was upgrade tendency between the Peff
      of duodenum, jejunum, ileum and colon in different concentration of daphnetin,
      and it has obvious difference between the high concentration and low
      concentration in jejunum and colon, which indicated that the absorption of
      daphnetin was passive diffusion and no difference in different segments of rat
      intestine. However, compared with colon, the absorption of small intestine was
      better significantly (P < 0.05). Daphnetin may be not a substrate of P-gp as
      verapamil had not significantly affected the absorption of daphnetin in different
      intestinal segments of rats.

PMID- 20055164
TI  - [TRAP analysis of Salvia miltiorrhiza Bge from different places of production].
AB  - The molecular maker system TRAP was utilized to develop a novel more accurate
      tool to identify the variety and establish the evolutionary relationship of
      different kind of Salvia miltiorrhiza Bge. PopGene 32 software was applied to
      conduct the cluster analysis and genetic dendrogram establishment. The results
      showed that 203 different fragments were amplified with 6 pair primers using the
      TRAP marker system. The polymorphic fragments number is 43, which takes up to
      21.1%. The cluster analysis shows that the 4 materials we used in this study can
      be classified into 2 main groups and 3 subgroups. The genetic identity is 0.0788
      and the average genetic distance is 0.9245 among the four materials in this
      study. A new tool using the TRAP marker system is more accurate and can be used
      to identify different kind of Salvia miltiorrhiza Bge at molecular level.

PMID- 20055165
TI  - [Analysis of the relationship between Glut-4 gene polymorphism and blood-fat
      traits in induced hyperglycemia mice].
AB  - This study is to investigate the effect of diet and gene on blood-fat trait of
      the individual mouse. One hundred and twenty mice were fed with high fat emulsion
      for 4 weeks. Then the genotypes of Glut-4 were analyzed by PCR-SSCP to
      investigate the effect on blood-fat traits and some organ performance of mice.
      After fed with high fat emulsion for 4 weeks, 98 mice suffered from
      hyperlipidemia, while 22 mice did not. And a T/A mutation was found in 188
      targeted fragments we amplified at 8,521 site, and association analysis showed
      that the mice carried BB genotype had higher TC, TG and LW/BW level than those of
      the mice with AA genotype (P < 0.05). Different Glut-4 genotypes show different
      sensitivities to high fat emulsion on mice.

PMID- 20055166
TI  - [Research progress of neuraminidase inhibitors for anti-influenza].
AB  - Influenza is a global contagious disease, which causes hundreds of thousands of
      people deaths. And new subtype of influenza may cause pandemic influenza, and
      lead to more serious consequence. Drugs for anti-influenza have played very
      important roles in influenza treatment and prevention, especially neuraminidase
      inhibitors are effective on both influenza A and B which have more safety and
      tolerance, therefore they have been widely used for influenza treatment. However,
      several viral drug-resistant cases have been reported. In this paper, the clinic
      therapy, prevention and drug resistance of neuraminidase inhibitors, including
      zanamivir, oseltamivir and peramivir, and progress in the research and
      development in our country are presented in order to promote research and
      development of new drugs for influenza treatment and prevention.

PMID- 20055167
TI  - Antibody-drug conjugates as targeted cancer therapeutics.
AB  - Traditional chemotherapy has become one of the essential treatments of cancer.
      However, cytotoxic agents are not tumor specific, which would cause serious side
      effects. Antibody-drug conjugates (ADCs), also called immunoconjugates, belong to
      the "targeted chemotherapeutics" category of anti-cancer drugs. ADCs are composed
      of three components including the cytotoxic drug, the monoclonal antibody, and
      the linker connecting the drug to the antibody. With the special-binding between
      antibody and antigen expressed on the surface of targeted cancer cells, ADCs
      provide a method to achieve excellent localization of the drug at the desired
      site in the body. The internalization and formation of ADCs are crucial in
      designing and applying an antibody conjugate to a particular disease model. In
      this review, we summarize three distinct internalization routes of ADCs and
      analysis the structure of ADCs. We also discuss in detail the categories and
      interaction of every component, as well as their influence to targeting property,
      liability and activity.

PMID- 20055168
TI  - [LEDGF/p75: a novel target for anti-HIV therapy and advances in the study of its
      related inhibitors].
AB  - LEDGF/p75 is a newly found cell cofactor, which plays an essential role in the
      integration of HIV-1 cDNA into host chromosomes. LEDGF/p75 tethers HIV integrase
      to chromatin, protects it from degradation, and strongly influences the genome
      wide pattern of HIV integration. Depleting the protein from cells or over
      expressing the integrase-binding domain of LEDGF/p75 blocks viral replication.
      The essential role of LEDGF/p75 in HIV-1 replication makes it a new target for
      anti-HIV-1 drug development. This article reviews the function of LEDGF/p75,
      LEDGF/p75-integrase interaction and LEDGF/p75 inhibitors.

PMID- 20055169
TI  - [Recent advances in the applications of ultrasonic microbubbles as gene or drug
      vectors].
AB  - With the research and application of the new ultrasound microbubble contrast
      agents, ultrasonic microbubbles can not only help to image, but they can also be
      used as genes or drug carriers. The microbubbles as genes or drug carriers can
      pass across the endothelial cell barrier and release genes and drug under the
      action of ultrasound field, which achieve target treatment effect. Based on the
      relevant materials, the bioeffects, early successes with gene and drug delivery,
      and potential clinical applications are reviewed.

PMID- 20055170
TI  - [Inhibitory effect of ginseng saponin IH901 on proliferation and metastasis of
      ECV304 cell line and its molecular mechanism].
AB  - This study aims to investigate the inhibitory effect on proliferation and
      metastasis of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH901) on
      ECV304 cell line. MTT assay was used to examine the effect of cell proliferation
      inhibition and the adhesive ability of ECV304 cells to artificial basement
      membrane. Morphology of cell apoptosis was observed with phase contrast
      microscope. Apoptosis rate and cell cycle were detected by flow cytometry (FCM).
      Cell migration was measured by wound healing assay. ELISA kit was used to detect
      VEGF and bFGF. Caspases were detected by Western blotting. Results indicated that
      ginseng saponin IH901 can downregulate the expression of growth promoting protein
      VEGF and bFGF, and upregulate pro apoptosis protein cleaved caspase-9 and cleaved
      caspase-3. The increase in the apoptotic sub-G1 fraction is in a dose-dependent
      manner, and cell cycle arrests in the G0/G1 phase was detected by FCM.
      Morphological examination of IH901-treated samples showed cells with chromatin
      condensation, cell shrinkage, and all typical characteristics of apoptotic cells.
      Therefore, IH901 dramatically suppresses cell proliferation and adhesion and
      migration of ECV304 cell line.

PMID- 20055171
TI  - Andrographolide inhibits hepatoma cells growth and affects the expression of cell
      cycle related proteins.
AB  - The present study is aimed to investigate the toxic effects of andrographolide
      (Andro) on hepatoma cells and elucidate its preliminary mechanisms. After cells
      were treated with different concentrations of Andro (0-50 micromol x L(-1)) for
      24 h, cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl) 2,5
      diphenyltetrazolium bromide (MTT) assay. Furthermore, after hepatoma cells (Hep3B
      and HepG2) were treated with different concentrations of Andro (0-30 micromol x
      L(-1)) for 14 d, the number of colony formation was accounted under microscope.
      Cell cycle related proteins such as Cdc-2, phosphorylated-Cdc-2, Cyclin B and
      Cyclin D1 were detected with Western blotting assay and the cell cycle was
      analyzed by flow cytometry using propidium iodide staining. MTT results showed
      that Andro induced growth inhibition of hepatoma cells in a concentration
      dependent manner but had no significant effects on human normal liver L-02 cells.
      Andro dramatically decreased the colony formation of hepatoma cells in the
      concentration-dependent manner. Moreover, Andro induced a decrease of Hep3B cells
      at the G0-G1 phase and a concomitant accumulation of cells at G2-M phase. At the
      molecular level, Western blotting results showed that Andro decreased the
      expression of Cdc-2, phosphorylated-Cdc-2, Cyclin D1 and Cyclin B proteins in a
      time-dependent manner, which are all cell cycle related proteins. Taken together,
      the results demonstrated that Andro specifically inhibited the growth of hepatoma
      cells and cellular cell cycle related proteins were possibly involved in this
      process.

PMID- 20055172
TI  - [Anti-proliferation of human cervical cancer HeLa cell line by fascaplysin
      through apoptosis induction].
AB  - This study is to investigate the effect of fascaplysin on human cervical cancer
      cells (HeLa) in order to provide insights into the mechanisms of growth
      suppression involved in fascaplysin-mediated apoptosis. Cytotoxic activity of
      fascaplysin on HeLa cells was determined using MTT assay, cell cycle analysis,
      and apoptosis (Annexin V-FITC and PI double staining) studies. The role of the
      molecules in cell cycle regulation and apoptosis was analyzed by Western blotting
      and flow cytometry. Fascaplysin markedly inhibited HeLa cells proliferation in a
      dose-dependent manner, however, did not provoke G1 phase arrest in HeLa cells
      with downregulation of CDK4, cyclin D1 and CDK4-specific Ser795 pRb
      phosphorylation. Furthermore, fascaplysin induced significantly apoptosis
      evidenced by sub-G1 peak and Annexin V-FITC and PI double staining. The molecular
      mechanism of fascaplysin-induced apoptosis was characterized with the activation
      of caspase-3, -8, and -9, truncation of Bid, release of cytochrome c into
      cytosol, and down-regulation of Bcl-2 level. Fascaplysin exhibits anti
      proliferation effect towards human cervical cancer HeLa cells through induction
      of apoptosis via extrinsic death pathway and mitochondrial pathway, but not
      arresting cell cycle progression at G1 phase. All together, these data sustain
      our contention that fascaplysin has anticancer properties and merits further
      investigation as a potential therapeutic agent.

PMID- 20055173
TI  - [Inhibitory action of Potentilla anserine polysaccharide fraction on H2O2-induced
      apoptosis of murine splenic lymphocytes].
AB  - A water-soluble polysaccharide fraction from root of Potentilla anserine was
      obtained. Gas chromatogram, FT-IR, physical and chemical characteristics of the
      Potentilla anserine polysaccharide fraction (PAPF) were analyzed. The protective
      effects of PAPF against the H2O2 induced process of apoptosis of murine splenic
      lymphocytes were investigated in vitro. Morphological assessment of apoptosis was
      performed with light microscope and laser scanning confocal microscope. DNA
      fragmentation was visualized by agarose gel electrophoresis. The amount of
      apoptotic cells was measured by flow cytometry. The results showed that PAPF is
      composed of rhamnose, arabinose glucose and galactose. H2O2 (200 micromol x L(
      1)) induced apoptosis of murine splenic lymphocytes with the cell volume reduced,
      cytoplasm and nuclear shrunk and DNA stained non-uniformly. Condensed chromatin
      and formation of apoptotic body were observed in the apoptotic cells. Apoptotic
      bodies in the cells treated with PAPF and H2O2 were less than those in H2O2
      treatment alone. DNA fragmentation assay showed that PAPF (50, 100, 200, and 400
      microg x mL(-1)) obviously reduced H2O2-induced ladder bands. Flow cytometry
      analysis showed that H2O2 increased the populations of apoptotic sub-G1 cells
      from 5.60% (control) to 45.40%, and PAPF decreased H2O2-induced apoptosis to
      37.80%, 22.70%, 17.70%, and 8.50%, respectively. In conclusion, PAPF reduced H2O2
      induced oxidative damage in a dose dependent manner.

PMID- 20055174
TI  - [Design and synthesis of nitrogen-containing benzoheterocyclic derivatives and
      their antipsychotic activities].
AB  - A series of nitrogen-containing benzoheterocyclic derivatives were synthesized
      and tested for their antipsychotic activities. Their structures were confirmed by
      1H NMR and HR-MS. Preliminary in vitro pharmacological trials showed that most of
      the target compounds have high affinity with D2 and 5-HT(2A) receptors. Among the
      tested compounds, 20 exhibited the highest affinity and D2 partial agonist
      activity. In vivo studies showed 20 has potent antipsychotic activities on
      apomorphine mice model, which is a chance to find a better precursor of D2
      partial agonist for further optimization.

PMID- 20055175
TI  - Pharmacophore modeling of dual angiotensin II and endothelin A receptor
      antagonists.
AB  - Three-dimensional pharmacophore models were generated for AT1 and ET(A) receptors
      based on highly selective AT1 and ET(A) antagonists using the program
      Catalyst/HipHop. Both the best pharmacophore model for selective AT1 antagonists
      (Hypo-AT(1)-7) and ETA antagonists (Hypo-ET(A)-1) were obtained through a careful
      validation process. All five features contained in Hypo-AT(1)-7 and Hypo-ET(A)-1
      (hydrogen-bond acceptor (A), hydrophobic aliphatic (Z), negative ionizable (N),
      ring aromatic (R), and hydrophobic aromatic (Y)) seem to be essential for
      antagonists in terms of binding activity. Dual AT1 and ET(A) receptor antagonists
      (DARAs) can map to both Hypo-AT(1)-7 and Hypo-ET(A)-1, separately. Comparison of
      Hypo-AT(1)-7 and Hypo-ET(A)-1, not only AT1 and ET(A) antagonist pharmacophore
      models consist of essential features necessary for compounds to be highly active
      and selective toward their corresponding receptor, but also have something in
      common. The results in this study will act as a valuable tool for designing and
      researching structural relationship of novel dual AT1 and ET(A) receptor
      antagonists.

PMID- 20055176
TI  - [A novel azo-type compound from Dendrolobium triangulare].
AB  - Thirteen compounds from Dendrolobium triangulare (Retz.) Schindl. were isolated
      and purified by chromatography on silica gel, macroporous resin column and
      recrystallization method, and their structures were elucidated by chemical and
      spectral analyses as azo-2, 2'-bis [Z-(2, 3-dihydroxy-4-methyl-5-methoxy) phenyl
      ethylene] (1), beta-sitosterol (2), N-(2'-hydroxy-tetracosanoyl)-2-amino-1, 3, 4
      trihydroxyoctadec-8E-ene (3), lupeol (4), cycloeucalenol (5), daucosterol (6),
      betulinc acid (7), betulin (8), glyceryl hexacosanoate (9), glyceryl 26-hydroxy
      hexacosanoate (10), methyl pheophorbide-a (11), acacetin-7-O-alpha-L
      rhamnopyranosyl (1-6)-beta-D-glucopyranoside (12) and robinin (13). To our
      knowledge, all compounds are obtained from Dendrolobium genus for the first time
      and compound 1 is a novel compound. Moreover, it is understood that compound 1
      has better protection against PC12 cell damnification deduced by glutamate, than
      that of Vitamin E in 2 microg x mL(-1) concentration.

PMID- 20055177
TI  - [Chemical constituents of Momordica charantia L].
AB  - Momordica charantia L. is a vegetable widely cultivated around the world. Its
      fruits have been used in Asian countries as a folk medicine for the treatment of
      non-insulin-dependent diabetes mellitus. Here we report eight compounds isolated
      from the fruits of M. charantia. On the basis of NMR and MS spectroscopic
      analyses, these compounds were identified as momordicolide ((10E)-3-hydroxyl
      dodeca-10-en-9-olide, 1), monordicophenoide A (4-hydroxyl-benzoic acid 4-O-beta-D
      apiofuranosyl (1 --> 2)-O-beta-D-glucopyranoside, 2), dihydrophaseic acid 3-O
      beta-D-glucopyranoside (3), 6,9-dihydroxy-megastigman-4,7-dien-3-one (blumenol,
      4), guanosine (5), adenosine (6), uracil (7) and cytosine (8). Among them, 1 and
      2 are new compounds. Compounds 3-5 were isolated from this plant for the first
      time.

PMID- 20055178
TI  - [Metabonomic study on the effects of allicin on rats].
AB  - To investigate the effects of allicin on rats by NMR-based metabonomic method,
      the changes of endogenous metabolites in normal rat urine and the influences on
      metabolism were analyzed with bio-nuclear magnetic resonance (NMR) method and
      partial least-squares discriminant analysis (PLS-DA) after intraperitoneal
      administration of allicin solution. The identified biochemical effects associated
      with allicin dosing included elevated then gradually recovered urinary levels of
      Kreb's cycle intermediates, such as citrate, alpha-ketoglutarate and succinate
      and increased concentrations of ketones. Meanwhile, decreased urinary
      concentrations of glucose, lactate, alanine, hippurate and trimethylamine oxide
      were observed. The PLS-DA revealed that the metabonomic profiles of allicin
      treated groups were obviously different from those of the control group. Allicin
      may change metabolism significantly in normal rats. The study of the
      pharmacologic mechanism of allicin by metabonomic method is practicable and it
      could be explored further.

PMID- 20055179
TI  - [Application of reversed-phase ion-pair chromatography for universal estimation
      of octanol-water partition coefficients of acid, basic and amphoteric drugs].
AB  - This paper is to establish a reversed-phase ion-pair chromatography (RP-IPC)
      method for universal estimation of the octanol/water partition coefficients
      (logP) of a wide range of structurally diverse compounds including acidic, basic,
      neutral and amphoteric species. The retention factors corresponding to 100% water
      (logk(w)) were derived from the linear part of the logk'/phi relationship, using
      at least four isocratic logk' values containing different organic compositions.
      The logk(w) parameters obtained were close to the corresponding logP values
      obtained with the standard "shake flask" methods. The mean deviation for test
      drugs is 0.31. RP-IPC with trifluoroacetic acid as non classic ion-pair agents
      can be applicable to determine the logP values for a variety of drug-like
      molecules with increased accuracy.

PMID- 20055180
TI  - [Evaluation of different combinations of components of Chinese formulation
      shuangshentongguan by using AUC values].
AB  - A sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was
      applied for the quantification of each component: tetrahydropalmatine (THP),
      dehydrocorydaline (DHC), salvianolic acid B (SAB), ginsenoside Rg1, Re, Rb1 and
      Rd in the Chinese herbal component SSTG (Shuangshentongguan) with different
      combinations. The pharmacokinetic data were analyzed with WinNonlin 5.2 software.
      The results showed that combination can increase the THP AUC value while the AUC
      values of SAB, ginsenoside Rg1, Re, Rb1 and Rd were reduced. These results showed
      significant differences. The AUC value of ginsenoside Rb1 was increased when
      combined with Danshen or Yanhusuo, but reduced when combined with Danshen and
      Yanhusuo. The DHC concentration in serum was too low to be determined.

PMID- 20055181
TI  - [Vascular endothelial cells targeted Tyr-RGD-PEG-PEI nano-drug synthesis and its
      biological activity].
AB  - The study is designed to synthesize nano-carrier Tyr-RGD (cyclo-[Arg-Gly-Asp-d
      Tyr-Lys]) and poly(ethylene glycol) modified polyethylenimine (Tyr-RGD-PEG-PEI)
      targeting vascular endothelial cells, then analyze its nanoparticle properties
      and the characteristics of drug carrying and targeting properties in vivo / in
      vitro tumor. The nano-carrier Tyr-RGD-PEG-PEI was synthesized with the method of
      chemical synthesis and the properties of this nanoparticle and drug carrying
      characteristics were identified. Its effect of targeting vascular endothelial
      cells in vitro was studied with the method of competitive binding assay. The
      fluorescent labeled nano-drug was injected into tumor-bearing nude mice to
      observe its tumor-targeting. The mean size of nano-carrier Tyr-RGD-PEG-PE was
      about 145 nm, good in encapsulation efficiency of siRNA. After incubation in
      plasma for half an hour, only about 3 percent of siRNA out. It was confirmed that
      it was a single spot with TLC analysis, the R(f) value was 0.65. Receptor
      competition experiments showed that the nano could effectively compete with RGD
      in binding the receptors on endothelial cells. Tumor-bearing nude mice
      experiments showed that when containing a fluorescent-labeled siRNA of Tyr-RGD
      PEG-PEI nano-drug was injected into mice, after 24 hours this nano-drug mainly
      distributed within the tumor tissue. However, nano-drug without Tyr-RGD appeared
      in tumor tissue as well as other organs such as livers, lungs, etc. The Tyr-RGD
      targeted gene vector Tyr-RGD-PEG-PEI synthesized in this study has good
      nanoparticle properties and high efficiency of gene-drug encapsulation. Study of
      nude mice shows that the ability of its tumor-targeting is significantly better
      than nano-drug without Tyr-RGD.

PMID- 20055182
TI  - [Isobutane driven salbutamol sulfate metered dose inhaler: formulation selection
      and respiratory tract absorption in guinea pigs].
AB  - This paper is to study the iso-butane (A-31)-driven salbutamol sulfate (SS)
      metered dose inhaler (MDI) formulations and inhaling status in guinea pigs.
      Solubility determination and orthogonal design were used to screen non
      chlorofluorocarbon (CFC) SS MDI formulations. Intubation inhalation of MDI in
      guinea pigs was used as a main administration method. Fluorescence HPLC detection
      method was testified as a potential method in assaying the concentration of SS in
      plasma of guinea pigs after inhaling various SS MDI formulations. Analysis of the
      data was executed with statistical moment calculation from which pharmacokinetic
      parameters were obtained. The results show that A-31 based on SS MDI formulations
      were screened and the guinea pigs in vivo determination method after inhaling SS
      MDI was established. The zero-moment rations of SS/A-31 MDI formulation to
      contrast sample and CFC SS MDI was 143.26% and 147.01%, respectively. The first
      moment value of SS/A-31 MDI formulation was the highest. It is a preliminary
      conclusion that the absorption result of SS/A-31 MDI formulation inhaled by
      guinea pigs is equivalent to HFA-134a formulation in sale and better than CFC
      formulation. A-31 could be used as a potential substitute candidate for CFC MDI
      propellant.

PMID- 20055183
TI  - [Preparation of enteric nanoparticles of Schisandra total lignanoids and
      preliminary study on its pharmacokinetics].
AB  - To study the preparation method of Schisandra total lignanoids enteric (SLE)
      nanoparticles and evaluate its pharmacokinetics in rats, SLE nanoparticles were
      prepared by modified emulsion solvent diffusion method. The properties of SLE
      nanoparticles were evaluated of morphology, mean diameter and entrapment
      efficiency. An HPLC method was employed to determine the concentration of
      deoxyschisandrin (QS) and schisantherin A (SA) in plasma, which were used as an
      index of Schisandra total lignanoids, and the bioavailability of the
      nanoparticles was compared with the reference group by oral administration using
      SD rats. The nanoparticles observed by transmission electronmicroscopy were
      round, and the mean particle sizes of SLE were (36.7 +/- 4.4) nm. Entrapment
      efficiency of QS and SA were (97.5 +/- 0.7)% and (91.3 +/- 0.8)%, respectively.
      Its pharmacokinetic process calculated with 3p97 software was fitted to a one
      compartment model. The pharmacokinetic parameters showed sustained-release
      property. Compared with reference formulation, the AUCs of SLE nanoparticles were
      2.3 and 5.8 times separately. These results suggested that the incorporation into
      Eudragit S100 of Schisandra total lignanoids can improve the bioavailability.

PMID- 20055184
TI  - [Analysis and authentication of chloroplast matK gene sequences of Herba
      Dendrobii].
AB  - To compare the characteristic of chloroplast matK gene sequences of different
      Herba Dendrobium species and to authenticate inspected species, the matK gene
      sequences of 12 species (including 22 materials) and outgroup were amplified,
      cloned, and sequenced. Genomic DNA of Dendrobium plants was extracted using
      modified cetyltrimethyl ammonium bromide (CTAB) method. The matK gene sequences
      were about 1 410 bp in length. The variable sites were 51 while the parsim
      informative sites were 11. There were nucleotides insertions and deletions in
      some species, in addition to transitions and transversions, such as in D.
      denneanum and D.chrysotoxum. Interspecies and different populations (varieties)
      of Dendrobium could be distinguished on phylogeny tree. The average genetic
      distance was 0.008, and the maximal and minimal genetic distances between
      Dendrobium species were 0.014 and 0.003, respectively. There were 8-20 variable
      sites between Dendrobium species. The genetic distance between populations
      (varieties) was 0.001, and there were 1-5 variable sites. Moreover, the 4
      inspected materials were successfully authenticated. The database of chloroplast
      matK gene sequences of 12 species of Herba Dendrobii and inspected species could
      be used for the molecular authentication between Dendrobium species and
      populations. The matK gene sequence could be used as molecular maker for
      authentication of Herba Dendrobium.

PMID- 20055185
TI  - [Pharmacokinetics of puerarin and hydrochlorothiazide from maijunan tablets in
      rats].
AB  - After oral administration of low, middle, high dose of simulative Maijunan
      tablets to SD rats and puerarin, hydrochlorothiazide at middle dosage to SD rats
      separately, plasma samples were collected at different times and treated with
      acetonitrile to precipitate protein. The contents of puerarin and
      hydrochlorothiazide in plasma were determined by HPLC method. The mean plasma
      concentration-time profiles of puerarin and hydrochlorothiazide at different
      dosages of medication administration were processed by 3P97 pharmacokinetic
      software and SPSS statistics 17.0 software. The results indicated that the in
      vivo kinetic processes of puerarin in rats were all fitted to a two-compartment
      open model and hydrochlorothiazide fitted to a one-compartment open model.
      Hydrochlorothiazide in vivo kinetic process in rats was in accordance with the
      linear dynamics. The combination of hydrochlorothiazide and rhynchophylla with
      pueraria promoted the absorption, reduced the elimination rate and prolonged the
      action time of puerarin in vivo. Meanwhile, the combination also promoted the
      absorption rate and the bioavailability, prolonged the action time and the
      accumulation time of hydrochlorothiazide in vivo.

PMID- 20055186
TI  - Double dip. HFMA, AHIP see losses in latest filings.

PMID- 20055187
TI  - Getting specific on M&A. New accounting rules offer added clarity to not-for
      profits.

PMID- 20055188
TI  - Largest patient-satisfaction measurement firms. Ranked by total number of
      engagements in 2008.

PMID- 20055189
TI  - [Practical research in morbid condition due to exogenous invasions for
      application in forensic diagnosis and preventive medical treatment].
AB  - We report research subjects on the morbid conditions due to various exogenous
      invasions, iatrogenic damages and suicide. The studies of morbid condition by
      exogenous invasions are as follows : 1) forensic significance of endocardial
      bleeding to diagnosing the causes of death, 2) forensic implication of
      intramuscular bleeding of the tongue of the fire victims, 3) stability of cyanide
      concentration in blood of the fire victims and the evaluation of the toxic
      potential, 4) histochemical detection of ABO blood type of the muscle of the fire
      victims by signal amplification method with biotinylated tyramide, 5) alcohol
      detection of purified brain tissue of the drowned victims and the estimation of
      the amount of drinking, and 6) investigation into unclosing a mechanism of
      postmortem production of endogenous gamma-hydroxybutyric acid(GHB). The
      researches for iatrogenic damages are as follows: 1) iatrogenic ribs fracture due
      to chest compression during cardiopulmonary resuscitation, 2) bone marrow
      embolism of the lung caused by iatrogenic ribs fracture, and 3) forensic
      application of lidocaine of blood and tissues, which is derived from xylocaine
      jelly, chemicals for surface anesthesia, frequently used with the purpose of
      lubricating effect when intubation tube is introduced into the trachea. The
      issues of suicide research aiming forensic and clinical application are as
      follows: 1) forensic significance of blood nicotine levels of the smokers who
      committed suicide, 2) forensic availability of muscle nicotine levels of the
      purified bodies who have suspected suicide, and 3) forensic value of analysis of
      chromogranin A mRNA in autopsy cases with various cause of death to diagnosing
      suicide.

PMID- 20055190
TI  - [Evaluation of the sexing methods using the cranial traits in the Japanese
      population].
AB  - Nowadays, various morphological traits are routinely used for sexing the human
      skulls. The efficacy and reliability of sexing methods based on these traits in
      the Japanese population have not been systematically investigated. For sexing the
      skull, the authors established the well-defined criteria for sexing skulls by
      using the following five morphological traits; (1) the prominence and texture of
      the supraorbital arc; (2) the sharpness of the supraorbital margin; (3) the
      relative size of the zygomatic arc and the existence of a depression on it; (4)
      the size of the mastoid process and the existence of the supramastoid crest; (5)
      the prominence of the external occipital crest and the external occipital
      protuberance, and then evaluated their availability by using 313 recent Japanese
      skulls (205 males and 108 females) with known sex and age-at-death. We found that
      the supraorbital arc had the best accuracy rate (80.5%) followed by the mastoid
      process (78.6%). In cases wherein these two morphological traits indicated the
      same sex, the accuracy rate increased to 96.3%, suggesting that these traits are
      particularly useful for sexing the skulls of Japanese individuals. In addition,
      the accuracy rate of most traits for sexing skulls significantly differed between
      individuals who were aged < 30 years at death and those who were in their 30s at
      death. Thus, the influence of aging on the morphological traits of the skulls
      should not be disregarded in Japanese population. Moreover, similar results were
      obtained when 120 Edo period Japanese skulls (74 males and 46 females) were
      studied. This indicates that our method is applicable not only to recent samples
      but also to the archaeological ones.

PMID- 20055191
TI  - [Statistical investigation on cases associated with medical implication in
      administrative autopsy within the 23 wards of Tokyo: the role of the medical
      examiner system in investigation of cases associated with medical implication].
AB  - Actual circumstances of administrative autopsies which proved connections between
      medical implication and death had not been very clear in the past. Therefore,
      using the records of administrative autopsies performed from 2003 to 2005 at
      Tokyo Medical Examiner's Office, this study looked into the cases in which a
      certain level of connection between medical implication and death was proved or
      suspected. This study dealt with 877 cases. The largest age group among the male
      was the one between 65 and 74, and the number of female cases increased as the
      age increased. The percentage of the studied cases among all the administrative
      autopsy cases has become larger after 2004. As regarding medical departments for
      implication, "internal medicine" had the largest number of the cases, and
      "unknown", "psychiatry", and "emergency" followed in order. 30 percent were being
      hospitalized during the final medical consultations, and the percentage went up
      to just over 60 when the deaths during and on the day after the final
      consultations were added to the figure. Regarding the causes of death, the great
      majority was natural death, and the other causes were 'unknown', 'fall', and
      'asphyxia'. Also, about 80 percent of the natural deaths were caused by
      circulatory, gastroenteric and respiratory diseases. Contradictions between
      clinical and forensic diagnoses were found in approximately 10 percent of the
      cases. In any case, medical examiners are to diagnose the causes of deaths by
      autopsy, not to evaluate the quality and safety of medical treatment. But if the
      quality and safety of medical treatment could be improved through the diagnoses
      of administrative autopsy, the medical examiner system would function practically
      as a part of administration for health and welfare. However, as it handles not
      only deaths by medical treatment but also all the other types of unnatural
      deaths, the system can also deal with other social problems, for which the
      correct causes of death must be diagnosed initially. It is socially very
      unhealthy to focus only on death associated with medical implication, as other
      types of unnatural death could be seen as relatively less important. Therefore,
      it is considered that the medical examiner system is effective for investigation
      of a variety of unnatural death as well as cases associated with medical
      implication.

PMID- 20055192
TI  - [Preoperative second-derivative of photoplethysmography measurement predicts the
      hemodynamic response to general anaesthesia induction].
AB  - BACKGROUND: Second-derivative of photoplethysmography (SDPTG) is a non-invasive
      method for the assessment of structural and functional arterial properties. We
      studied the hemodynamic responses to induction of anaesthesia and whether SDPTG
      could be used in predicting these responses. METHODS: SDPTG was performed in 71
      subjects (35 males, 36 females) undergoing general anaesthesia for elective
      operation. Anaesthesia was inducted with propofol 2 mg x kg(-1), fentanyl 2
      microg x kg(-1), vecuronium 0.1 mg x kg(-1), and sevoflurane 3% in a mixture of
      100% oxygen. RESULTS: The SDPTG indices (b/a and d/a values) significantly
      correlated with the percentage decrease in systolic blood pressure in both
      genders. Regression equations (x = SDPTG indices, y = percentage of decrease in
      systolic blood pressure) were as follows: (1) b/a, r(male) = 0.39, P < 0.05, y =
      23.26x + 40.67; r(female) = 0.39, P < 0.05, y = 17.95x + 39.61; (2) d/a, r(male)
      = -0.37, P < 0.05, y = -31.29x + 16.22 and r(female) = -0.48, P < 0.01, y = 
      34.46x + 18.55. CONCLUSIONS: These results suggest that preoperative SDPTG is
      useful in predicting the hemodynamic response to induction of general
      anaesthesia.

PMID- 20055193
TI  - [Effect of dexmedetomidine on anesthetic requirements in cardiovascular surgery].
AB  - BACKGROUND: An anesthetic-sparing effect of dexmedetomidine has been shown in
      several studies. We investigated the effect of dexmedetomidine on anesthetic
      requirements in 24 patients undergoing cardiovascular surgery. METHODS: Patients
      were randomly divided into two groups in which continuous infusion of
      dexmedetomidine was started before induction of anesthesia (DEX group, n = 12) or
      when closing the sternum (control group, n = 12). Dexmedetomidine was
      administered intravenously at 0.7 microg x kg(-1) x hr(-1) after a bolus infusion
      at 6.0 microg x kg(-1) x hr(-1) for 10 min. All patients received total
      intravenous anesthesia with propofol and fentanyl. RESULTS: Mean effect-site
      concentration of propofol was significantly lower in the DEX group than in the
      control group (1.9 +/- 0.3 microg x ml(-1) vs 2.5 +/- 0.8 microg x ml(-1)). Mean
      effect-site concentration of fentanyl in the DEX group was significantly lower
      than that in the control group (1.93 +/- 0.41 ng x ml(-1) vs 2.67 +/- 0.70 ng x
      ml(-1). CONCLUSIONS: The combined use of dexmedetomidine decreases anesthetic
      requirements in cardiovascular surgery.

PMID- 20055194
TI  - [Postoperative analgesia for the laparoscopic cholecystectomy].
AB  - BACKGROUND: As laparoscopic cholecystectomy is assumed to be with less
      postoperative pain, it is managed only by general anesthesia during the surgery
      in our hospital. However, about 70 percent of cases needed the additional
      analgesic drugs after the operation. In addition, about 70 percent needed
      analgesic drugs within three hours after the operation, and it has been
      understood that early postoperative analgesia is insufficient. We focused on the
      ultrasound guided nerve block and used it to relieve postoperative pain after the
      laparoscopic cholecystectomy. METHODS: Forty three cases managed by the general
      anesthesia alone are compared with 9 cases managed with the nerve block of the
      trunk in for the laparoscopic cholecystectomy. RESULTS: Pain score early after
      the operation, the ratio of patient who used analgesic drug, and the frequency of
      its use are all decreased by performing the block. CONCLUSIONS: The use of
      ultrasound guided nervous block for the postoperative pain after laparoscopic
      cholecystectomy has been helpful, and excellent pain relief has been obtained.

PMID- 20055195
TI  - [Ultrasound-guided and fluoroscopy-assisted selective cervical nerve root
      blocks].
AB  - BACKGROUND: In this article, we describe 14 case reports of using ultrasound
      guidance to facilitate blockade of the cervical nerve root. METHODS: A total of
      14 ultrasound-guided selective cervical nerve root blocks using fluoroscopy were
      performed in 10 patients. The target point was the spinal nerve root between the
      anterior and posterior tubercles of the most lateral aspect of the transverse
      process C3-7, and C8 nerve root on the first rib. The key landmark was the C7
      vertebra because of the absence of the anterior tubercle. RESULTS: All of the
      ultrasound-guided needles were placed accurately. There were no intravascular
      injections under real-time fluoroscopy. There were no complications. CONCLUSIONS:
      We conclude that ultrasound guidance might be useful for cervical nerve root
      blocks by improving nerve and vascular localization, and injections under real
      time fluoroscopy might make this block safer by identification of the
      intravascular injection.

PMID- 20055196
TI  - [Effects of intravenous midazolam, fentanyl or ketamine on pain relief during
      performance of epidural anesthesia].
AB  - BACKGROUND: Performing epidural anesthesia is accompanied by pain. The aim of
      this study is to examine whether intravenous administration of a sedative, an
      opioid, or an anesthetic eliminates pain score during the epidural procedure.
      METHODS: Two-hundred and fifty-nine patients undergoing epidural anesthesia were
      randomly allocated into six groups. Prior to the epidural anesthesia, midazolam,
      fentanyl, ketamine, midazolam plus fentanyl or midazolam plus ketamine was given
      intravenously to the patients in each group. After the procedure, the effects of
      these drugs on pain relief in the patients were assessed by visual analogue
      scale(VAS). RESULTS: VAS was significantly decreased in all drug-treated groups
      to a similar extent, as compared with drug-free group. There was no significant
      difference between the drug-treated groups. Serious side effects including
      persistent respiratory suppression were not observed in this study. CONCLUSIONS:
      The findings obtained from this study suggest that the analgesic action of the
      drug is not essential to the pain relief and the anxiolytic action is important
      for the epidural procedure.

PMID- 20055197
TI  - [Postoperative nausea, vomiting and pain after pediatric outpatient surgery :
      comparison of laparoscopic and conventional inguinal hernia repair].
AB  - BACKGROUND: The number of laparoscopic surgery is increasing in pediatric
      surgery. There are few studies in which the pediatric outpatient postoperative
      course was compared between the laparoscopic and conventional open surgery.
      METHODS: Girls older than 1 year who had undergone outpatient hernia repair
      between August 2005 and November 2006 were retrospectively reviewed dividing into
      2 groups according to the procedures. The girls in Group L underwent laparoscopic
      percutaneous extraperitoneal closure (LPEC) (n = 53) and girls in Group P
      underwent conventional Potts procedure (n = 48). In all the patients anesthesia
      was induced and maintained with sevoflurane and nitrous oxide in oxygen. Airway
      was secured either by tracheal intubation or laryngeal mask airway without the
      use of muscle relaxants. All the patients received ilioinguinal nerve block and
      the patients in group L received additional paraumbilical nerve block. RESULTS:
      The operation time and anesthesia time were longer in group L. The patients in
      group L had a higher incidence of nausea (30.2% vs. 12.5%, P < 0.01) and vomiting
      (22.6% vs. 10.4%, P < 0.05) and required more analgesics (39.6% vs. 23.0%, P <
      0.01) compared with those in group P. The incidence of unplanned hospital
      admission was not different between the groups. CONCLUSIONS: The patients
      undergoing LPEC required more postoperative analgesics. The measures to lower
      postoperative nausea and vomiting should be adopted in these patients.

PMID- 20055198
TI  - [Case of failed spinal anesthesia for cesarean section caused by spinal arachnoid
      cyst].
AB  - A 27-year-old pregnant woman was scheduled for cesarean section under spinal
      anesthesia. Although there was no trouble in three repeated spinal punctures, the
      anesthetic effect was insufficient. Then we changed anesthetic management to
      general anesthesia. There was no postoperative neurological complications related
      to spinal anesthesia. Postoperatively, spinal arachnoid cyst was found by MRI.
      The cyst was thought to have caused insufficient analgesic effect of spinal
      anesthesia in this patient.

PMID- 20055199
TI  - [Perioperative management for transurethral resection of bladder tumor (TUR-Bt)
      associated with congenital antithrombin III deficiency].
AB  - Congenital antithrombin III (ATIII) deficiency is a hereditary disease that
      predisposes to thromboembolic complications. We report perioperative management
      for twice in a patient with congenital ATIII deficiency. A 69-year-old man with
      congenital ATIII deficiency, with history of deep vein thrombosis (DVT) in his
      left popliteal vein, was scheduled for transurethral resection of bladder tumor
      (TUR-Bt). The plasma ATIII activity was 57% of normal vale. As ATIII concentrates
      3,000U per day had been administered intravenously since the second day before
      the operation, the plasma ATIII activity was 147% on the operation day. TUR-Bt
      was performed in the lithotomy position under general anesthesia. ATIII
      concentrates 3,000 U per day were administered intravenously for two days after
      the operation and low molecular weight heparin (LMWH) 2,500 U per day was
      administered subcutaneously for five days after the operation. One year later he
      had a recurrence of bladder tumor. The plasma ATIII activity was 54%. ATIII
      concentrates 3,000 U per day had been administered intravenously since the three
      days before the operation. The second TUR-Bt was also performed in the lithotomy
      position under general anesthesia. ATIII concentrates 1,500 U per day were
      administered intravenously for three days after the operation. LMWH was not
      administered due to postoperative bleeding from the bladder. He had no
      thromboembolism during each perioperative period. The lithotomy position with
      fixation of both hips and both knees may decrease venous blood flow, increase
      muscle compartment pressure of the lower extremities, predispose to DVT in the
      lower extremity, and lead to pulmonary thromboembolism (PE). Control of blood
      coagulation and maintenance of sufficient venous blood flow in the lower
      extremities with ATIII adjuvant therapy and LMWH administration during the
      perioperative period are important for TUR-Bt in a patient with congenital ATIII
      deficiency to prevent DVT and PE.

PMID- 20055200
TI  - [Case of autonomic hyperreflexia treated with intravenous nicardipine].
AB  - We describe a case of 26-year-old male patient with autonomic hyperreflexia (AH)
      during colostomy. He had suffered paraplegia due to the 8th cervical spinal cord
      injury by a traffic accident 2 years before. The anesthesia was induced and
      maintained with propofol, fentanyl, ketamine and vecuronium. Vital signs
      including blood pressure (135-145/70-80 mmHg) and heart rate (55-65 beats x min(
      1)), were stable at the beginning of the operation. However, blood pressure
      suddenly rose (220/ 120mmHg), and heart rate decreased (43 beats x min(-1))
      associated with skin eruptions on his face and shoulder when the intestinal tract
      procedure was started. Diagnosis of AH was made. Then nicardipine 1 mg i.v. was
      given followed by nicardipine 2 microg x kg(-1) x min(-1) DIV Consequently, blood
      pressure (140-155/ 70-85 mmHg) and heart rate (75-85 beats x min(-1)) were
      stabilized. The operation was finished with no evidence of any complications.
      Nicardipine may be preferable in a patient with upper spinal cord injury
      undergoing operation in the paralyzed area.

PMID- 20055201
TI  - [Serotonin syndrome caused by an overdose of dextromethorphan, Medicon].
AB  - We report the first case of serotonin syndrome caused by overdose of
      dextromethorphan in Japan. A 34-year-old woman with schizophrenia received a
      dextromethorphan (Medicon) for a catarrhal symptom from two individual
      departments of the university hospital by chance. The daily amount of
      dextromethorphan was up to 180 mg for several days in addition to other regular
      antipsychotic drugs including risperidone, amitriptyline and levomepromazine.
      Finally, she was found in deep comatose state (GCS coma scale: E1V1M1) and the
      trachea was intubated in the emergency room. After admission to intensive care
      unit, the consciousness gradually improved; however, she was confused and
      agitated. The situation was normalized within next 24 hours and she was weaned
      from the mechanical ventilation next day. Serotonin syndrome demonstrates various
      signs and might be overlooked in an emergency room. Dextromethorphan is
      considered as a safe antitussive drug; however, the unexpected interaction should
      be suspected during chronic medical treatment.

PMID- 20055202
TI  - [Apnea and severe respiratory depression induced by dexmedetomidine after general
      anesthesia in intensive care unit].
AB  - Dexmedetomidine (DEX) is widely used in intensive care unit for perioperative
      sedation. The one advantage of DEX administration for sedation is the lack of
      significant respiratory depression. However, DEX shows significant interaction
      with anesthetics and narcotics, and we present a case in which post-anesthetic
      administration of DEX induced apnea and severe respiratory depression after
      extubation. A 74-year-old, 38.3 kg, 148 cm woman was scheduled to undergo
      implantation of internal cardiac defibrillator. General anesthesia was maintained
      by sevoflurane, remifentanil and intermittent administration of fentanyl. After
      the surgery, she was transferred to intensive care unit with intubation, and DEX
      administration was commenced. After 3.5 hr from the end of anesthesia, the
      patient's trachea was extubated under continuous infusion of DEX (0.26 microg x
      kg(-1) x hr(-1)). Ninety min later, she showed apnea and severe respiratory
      depression. The interaction of DEX and residual narcotics might have induced life
      threatening respiratory complication.

PMID- 20055203
TI  - [Case of myocardial infarction during emergency clipping surgery of a cerebral
      aneurysm].
AB  - An 80-year-old woman with subarachnoid hemorrhage underwent emergency neck
      clipping of a cerebral aneurysm. She had previously undergone surgery for an
      abdominal aortic aneurysm 10 years before. Anesthesia was induced with propofol
      and maintained with a combination of fentanyl and sevoflurane (0.5-1.5%) in air
      and oxygen. Ventricular fibrillation occurred immediately before clipping of the
      aneurysm, in the absence of preexisting myocardial ischemia, and recurred 4 times
      thereafter during the surgery. The ventricular fibrillation was successfully
      treated with cardioversion. We administered catecholamines, nitrates, calcium
      antagonists, nicorandil and heparin, following which the patient's hemodynamics
      gradually improved. After the operation, the patient was transferred to the
      cardiovascular center of a neighboring university where she successfully
      underwent emergency percutaneous transluminal coronary angioplasty. The patient
      was discharged from hospital 10 days later without any complications. Patients
      undergoing vascular surgical procedures or having a preoperative history of prior
      vascular surgery are at high risk for perioperative myocardial infarction. It is
      necessary to perform cardiac examination, including coronary angiography,
      preoperatively in such patients, even in those who are otherwise asymptomatic.

PMID- 20055204
TI  - [Case of thyroid crisis with persistent tachycardia diagnosed postoperatively].
AB  - A 35-year-old man with multiple bone fractures underwent an emergency operation.
      On arriving at the operating room, his heart rate was 160 beats x min(-1), and
      blood pressure was 100/50 mmHg. We anesthetized him with oxygen, sevoflurane,
      fentanyl and remifentanil. We suspected hypovolemia, and treated him with
      crystalloid and transfused red cells and fresh frozen plasma so that heart rate
      and blood pressure could be stabilized. Tachycardia of 140 beats x min(-1)
      persisted, and landiolol was continuously administered at a rate of 5-10 mg x hr(
      1) after a 2.5 mg bolus injection. Heart rate became controlled around 120 beats
      x min(-1) without hypotension during anesthesia. Finally, we noticed thyroid
      crisis in this case, and diagnosed it with laboratory data after operation. We
      should be aware that atypical tachycardia is caused by thyroid crisis.

PMID- 20055205
TI  - [Case of submucosal hematoma of the esophagus noticed postoperatively].
AB  - We experienced a case of submucosal hematoma of the esophagus noticed after
      cervical anterior spinal fusion (ASF) between C7 and T1 for ossification of
      posterior longitudinal ligament (OPLL). The patient was a 68-year-old man, and no
      abnormality was found in the preoperative examinations. Anesthesia was induced
      and maintained with remifentanil, propofol and vecuronium. Tracheal intubation
      was performed using fiberscope uneventfully, and gastric tube and esophageal
      stethoscope were inserted into the esophagus smoothly. The operation was
      completed in 7 hours and 10 minutes. When we removed the gastric tube and the
      esophageal stethoscope after the operation, no bloody secretion was noticed. The
      next day, the patient complained of melena, and gastrointestinal endoscopy showed
      a submucosal hematoma extending from the posterior wall of the cervico-thoracic
      border in the esophagus to the cardia. Submucosal hematoma of the esophagus is a
      rare complication. In this case, surgical procedure was suspected to have caused
      the hematoma, since the upper end of the hematoma corresponded to the surgical
      field.

PMID- 20055206
TI  - [Energy expenditure of anesthesiologists estimated from number of steps].
AB  - The physical activity can be mainly evaluated by the number of steps. We
      estimated the energy expenditure from the number of steps in the different job
      specifications of anesthesiologists using digital pedometer Walk Life CH-200
      (Crecer Co, Tokyo, Japan). The average number of steps in the anesthesiologists
      (n = 41, 31 +/- 5 yr. old, M/F = 34/7, body mass index (BMI) 23 +/- 4 kg x m(-2)]
      during daily working hours was 7,778 and almost as same as the average number of
      steps in Japanese people for one day or manufacturer during daily working hours.
      The average numbers of steps in the residents (n = 26, 29 +/- 4 yr. old, M/F =
      20/6, BMI 21 +/- 2 kg x m(-2)), instructors (n = 10, 35 +/- 5 yr. old, M/F = 9/1,
      BMI 24 +/- 4 kg x m(-2)), and supervisors (n = 5, 38 +/- 6 yr. old, M/F = 5/0,
      BMI 27 +/- 3 kg x m(-2)) were 7,249, 8,399, and 11,599, respectively. The number
      of steps in supervisor was significantly more than resident. Our present findings
      about the numbers of steps in the anesthesiologists were contrary to the general
      reports that the number of step in manager is less than laborer and the number of
      step decreases with aging and increasing BMI. No sex difference with the numbers
      of steps in anesthesiologists was contrary to the general report that the number
      of step in male is more than female. From our present results, the energy
      expenditure estimated from the number of steps in anesthesiologists, residents,
      instructors, and supervisors might correspond to 285, 246, 331, and 516 kcal,
      respectively.

PMID- 20055207
TI  - [Trends of HIV patients operated at International Medical Center of Japan].
AB  - BACKGROUND: HIV-infected patients are on the increase in Japan, and anti-HIV
      therapy improved their prognosis. It is expected that the number of operations in
      HIV patients will increase. METHODS: We surveyed the prevalence of HIV 30,188
      patients operated at International Medical Center of Japan, a major, HIV/AIDS
      hospital, from 2001 to 2007. RESULTS: The number of HIV-positive cases was 389 in
      7 years, and the prevalence of HIV seropositivity was 1.3% in total, 1.0% in
      scheduled, and 2.0% in emergent cases. The prevalence of male (2.0%) was higher
      than female (0.7%) patients and the prevalence was highest (9.2%) in male
      patients in their 30's. They were parallel with the HIV occurrence trend of
      Japan. The prevalence was the highest (2.4%) in the division of general surgery,
      as well as in obstetric and gynecology. The number of major surgery in HIV
      patients has been increasing. CONCLUSIONS: We assume that the perioperative
      management in each hospital has become more important. The annual trend of the
      number of the operations performed in HIV-positive patients at our hospital did
      not show annual changes.

PMID- 20055208
TI  - [Survey on the nurses' awareness of postoperative pains in children in a
      university hospital].
AB  - BACKGROUND: Since children often have difficulty in expressing pains accurately,
      it is more important in child than in adult that physicians and nurses share the
      awareness of postoperative pains in children and provide care by paying attention
      to the methods of evaluating pains and analgesia. METHODS: Awareness and current
      status of postoperative pains in children were surveyed by a questionnaire to
      nurses working at a university hospital. RESULTS: More than 90% of nurses
      answered positively towards the necessity of postoperative analgesia in children.
      In terms of satisfaction as to postoperative analgesia, more than 80% of nurses
      answered that they were able to provide it "as much as they could". However, when
      analgesic measures that were indeed provided were asked, it turned out that the
      contents of analgesic methods "as much as they could" differed among wards.
      CONCLUSIONS: Despite the high awareness of postoperative pains in children, it
      turned out that putting them into practical use was difficult in some wards of
      the university hospital. Since major educative institutes for nurses are
      university hospitals in Japan, it was thought to be important for physicians and
      nurses working there to try to further share the awareness of postoperative pains
      in children.

PMID- 20055209
TI  - [Incidence and characteristics of perioperative pulmonary thromboembolism in
      Japan from 2005 through 2007--results of research by Japanese Society of
      Anesthesiologists, Committee on Patient Safety and Risk Management, Perioperative
      Pulmonary Thromboembolism Working Group].
AB  - BACKGROUND: This study aimed to investigate the annual incidence and
      characteristics of perioperative pulmonary thromboembolism (PTE) in Japan from
      2005 through 2007, and to compare the current trend with that observed in our
      previous studies conducted since 2002. METHODS: In the 3-year study period, a
      questionnaire was annually mailed to every institution certified as a training
      hospital for anesthesiologists by the Japanese Society of Anesthesiologists
      (JSA). The survey included the parameters of age, sex, type of surgery, and the
      risk factors in patients who were operated upon. RESULTS: The average rate of
      effective responses was 55.1%, and a total of 825 cases of perioperative PTE were
      registered in the 3-year study period. The incidence of perioperative PTE was
      2.79 per 10,000 cases in 2005, 2.25 per 10,000 cases in 2006, and 2.57 per 10,000
      cases in 2007. The incidence of PTE in all the 3 years was significantly lower
      than that observed in 2002-03 (P < 0.01). In addition, the incidence of fetal PTE
      in 2006 and 2007 was also significantly lower than that in 2002-03. The incidence
      of PTE in older persons (66-85 years) was approximately twice (4.70 per 10,000
      cases) and that in the oldest persons (> 86 years) was approximately thrice (6.28
      per 10,000 cases) the incidence in middle-aged individuals (2.17 per 10,000
      cases). PTE was found to be more frequent in females than in males (males, 1.89
      per 10,000 cases; females, 3.75 per 10,000 cases). The types of surgery that most
      commonly resulted in perioperative PTE were limb and/or hip joint surgery (5.57
      per 10,000 cases), thoracotomy with laparotomy (5.19 per 10,000 cases), and
      spinal surgery (4.49 per 10,000 cases). Perioperative PTE was fatal in 185
      patients (22.4%), and the mortality rate of patients who had not received
      prophylaxis was significantly higher (37.8%) than that of patients who received
      anticoagulant drugs (20.8%). Guidelines for prevention of perioperative PTE were
      accepted by 58% of all training institutions. CONCLUSIONS: The incidence of
      perioperative PTE and fetal PTE has currently decreased; however, prophylaxis
      with anticoagulant drugs may have reduced the mortality in some cases.

PMID- 20055210
TI  - Women's appraisals of intimate partner violence stressfulness and their
      relationship to depressive and posttraumatic stress disorder symptoms.
AB  - Intimate partner violence (IPV) increases risk for depressive and posttraumatic
      stress disorder (PTSD) symptoms. Most studies use a dose-response approach to
      examine the impact of IPV on mental health, but they often fail to explain mental
      health outcome specificity as well as to assess the impact of women's subjective
      appraisals. The present research examined women's IPV stressfulness appraisals
      and their psychological functioning (depressive and PTSD symptoms). Results
      indicate that IPV stressfulness appraisals are associated with depressive
      symptoms over and above frequency and severity of IPV. PTSD symptoms were
      associated with frequent and stressful IPV. Women who experienced highly frequent
      and highly stressful IPV were most likely to display comorbid depressive and PTSD
      symptoms. Results underscore the importance of women's subjective experiences and
      the heterogeneity of women's responses to IPV.

PMID- 20055211
TI  - Rape reporting: "Classic Rape" and the behavior of law.
AB  - Two theories of rape reporting, the Classic Rape perspective and Black's Theory
      of the Behavior of Law, are tested in this article. We offer the first
      comprehensive multivariate test of Classic Rape predictions among a nationally
      representative sample of victims, as well as the first test of Black's
      predictions for rape reporting. Through the construction of multinomial
      regression models, we are able to examine reporting patterns for both victims and
      third parties. Weapon use and physical injury consistently predicted reporting.
      The likelihood of victim reporting significantly increased when assaults occurred
      either in public or through a "home blitz," whereas place of assault did not
      affect the likelihood of third-party reporting. On the other hand, victim
      offender relationship significantly affected the likelihood of third-party
      reporting but was not significant in the victim-reporting models. There were
      mixed findings regarding Black's stratification and morphology predictions, and
      we found no significant effects for culture, organization, or social control.
      Overall, these findings lend greater support to the Classic Rape perspective than
      to Black's model.

PMID- 20055212
TI  - Prevalence and correlates of intimate partner violence victimization among men
      and women entering substance use disorder treatment.
AB  - Intimate partner violence victimization was examined in men (N = 4,459) and women
      (N = 1,774) entering substance use disorder treatment. Nearly 1 in 2 women and 1
      in 10 men reported lifetime victimization by an intimate partner. Entering
      treatment for alcohol, as compared to drug abuse and history of childhood abuse,
      were each associated with intimate partner violence victimization. Victimization
      by an intimate partner was also associated with mental health problems, including
      depression, anxiety, and attempted suicide. Although victimization was linked to
      physical health problems, the nature of these problems varied by gender. Women
      and men with a history of intimate partner victimization present to substance use
      disorder treatment with a complex array of mental and physical health problems.

PMID- 20055213
TI  - Batterer intervention programs: a report from the field.
AB  - Over the past 25 years, batterer intervention has become the most probable
      disposition following a plea or conviction on domestic battery charges and,
      consequently, batterer intervention programs (BIPs) have proliferated. Despite
      their popularity, and recent attempts by states to regulate practice, little is
      known about the actual programs operating in the field. The aim of this study was
      to examine the philosophy, structure, leadership, curricula, and support systems
      of BIPs. Respondents from 276 batterer intervention programs in 45 states
      described their programs via an anonymous, Web-based survey. The results provide
      some insight regarding the workings of actual BIPs and also point out problems
      such as the dearth of programs in languages other than English and the failure to
      translate recommendations for prescriptive approaches into practice.

PMID- 20055214
TI  - Correlates for legal help-seeking: contextual factors for battered women in
      shelter.
AB  - Legal redress can play a critical role in interrupting the pattern of domination
      and control inherent in intimate partner violence (IPV), yet it remains an
      infrequent strategy among battered women. The current study employed a contextual
      framework for investigating the correlates for engagement in the criminal justice
      system for a sample of 227 sheltered battered women. Results indicated that
      individual, relational, and system-level factors were all associated with two
      legal help-seeking behaviors: having a civil protection order and criminal
      prosecution. In particular, posttraumatic stress disorder (PTSD) symptomatology,
      social support, and prior experience with police officers were significant
      correlates for legal help-seeking. Results highlight the need for a coordinated
      community response to IPV, addressing both legal needs and psychological needs
      simultaneously.

PMID- 20055215
TI  - Posttraumatic stress symptoms as a mediating factor on the effects of exposure to
      community violence among children in Cape Town, South Africa.
AB  - Research conducted over the past 20 years has linked exposure to violence to
      posttraumatic stress disorder (PTSD) in children both in the United States and
      South Africa, but very little research has investigated PTSD as a mediating
      variable between exposure to violence and other problems. The purpose of the
      current research was to determine if PTSD acts as a mediating variable between
      exposure to violence and depression, and exposure to violence and aggressive and
      violent behavior at school among a sample of 247 South African children.
      Regression analysis suggested that PTSD mediated the effects of exposure to
      violence on depression, whereas the effect of exposure to violence on aggression
      and violent behavior was only direct. The findings are discussed in terms of
      their implications for intervention and treatment.

PMID- 20055216
TI  - Feelings of safety inside prison among male inmates with different victimization
      experiences.
AB  - Correctional facilities have a responsibility to take "reasonable measures" to
      preserve and protect inmate safety. The extent to which people inside prison feel
      safe from victimization is explored using a sample of approximately 7,000 adult
      male inmates housed in 13 prisons. The majority of male inmates reported no
      victimization in the past 6 months and that they felt safe, especially from
      sexual abuse and assault. Levels of feeling safe diminished for inmates who
      experienced victimization. Inmate perceptions of safety varied between
      facilities. Variation in perceptions of safety among harmful situations and
      between facilities provides useful information about inmate safety and ways to
      improve it (n = 104).

PMID- 20055217
TI  - Exploring Mexican-origin intimate partner abuse survivors' help-seeking within
      their sociocultural contexts.
AB  - Women's responses to partner abuse are shaped by their particular sociocultural
      contexts. In this study, quantitative data were collected from 75 Mexican-origin
      women who survived intimate partner abuse, to identify variables associated with
      help-seeking to survive relationship abuse. Help-seeking was defined as use of
      formal (e.g., shelter) and informal (e.g., family) sources. Variables included
      two cultural variables: machismo (i.e., adherence to traditional gender roles)
      and familismo (i.e., valuing family cohesion and reciprocity), and four
      sociostructural variables: income, education, English proficiency, and immigrant
      status. Results indicated participants with higher levels of familismo sought
      informal help more frequently than those with lower levels. Women with grade
      school education, no English proficiency, and undocumented status sought formal
      help less frequently than those not constrained by these barriers.

PMID- 20055218
TI  - Identification of heterotrophic plate count bacteria isolated from drinking water
      in Japan by DNA sequencing analysis.
AB  - Heterotrophic plate count (HPC) test has been employed to indicate the
      effectiveness of water treatment processes and the microbiological condition of
      the distribution system. In Japan, because the majority of HPC bacteria are
      supposed to be harmless and all tap water should maintain residual chlorine,
      there are few studies of the virulence of HPC bacteria. In this study, we
      examined HPC bacteria isolated from finished and tap water for hemolytic activity
      to determine their virulence potential. 34 of 39 colonies expressing hemolytic
      activity were identified by partial 16S rDNA sequencing, but some of their
      percent identity were relatively low. This may have been due to the mismatching
      of the primer pair with some strains, or these strains may be unidentified new
      species. A total of 30 of 34 isolates identified have been reported to be
      opportunistic pathogens or food poisoning bacteria. To control the growth of
      these opportunistic pathogens among HPC bacteria, appropriate water quality
      control must always be done and residual chlorine must be maintained in every tap
      for a safe water supply.

PMID- 20055219
TI  - Inactivation of feline calicivirus, a norovirus surrogate, by chlorine dioxide
      gas.
AB  - The efficacy of gaseous chlorine dioxide (ClO2) against feline calicivirus (FCV),
      a norovirus surrogate, in the dry and the wet states on a hard surface was
      evaluated. We demonstrated that low-concentration ClO2 gas (mean 0.08 ppm, 0.22
      microg/I) could inactivate FCV in the wet state with 0.5% fetal bovine serum
      (FBS) within 6 h in 45 to 55% relative humidity (RH) (> 3 log10 reductions) and
      FCV in the dry state with 2% FBS (percentage of FBS in the viral suspension)
      within 10 h in 75 to 85% RH (> 3 log10 reductions) at 20 degrees C, respectively.
      Furthermore, a < 0.3 ppm concentration of ClO2 gas (mean 0.26 ppm, 0.73 microg/l)
      could inactivate (below the detection limit) FCV in the dry state with 5% FBS
      within 24 h in 75 to 85% RH at 20 degrees C. In contrast, in 45 to 55% RH at 20
      degrees C, ClO2 gas had little effect even when the FCV in the dry state was
      exposed to high-concentration ClO2 (mean 8 ppm, 22.4 microg/l) for 24 h. These
      results suggest that humidity plays an important role in the inactivation by ClO2
      gas of FCV in the dry state. According to the International Chemical Safety Card,
      threshold limit values for ClO2 gas are 0.1 ppm as an 8-h time-weighted average
      and 0.3 ppm as a 15 min short-term exposure limit. From these data, we propose
      that the treatment of wet areas of human activity such as kitchens, toilets,
      etc., with low-concentration ClO2 gas would be useful for reducing the risk of
      infection by noroviruses (NV) without adverse effects. In addition, we believe
      that the application of a combination of a < 0.3 ppm concentration of ClO2 gas
      and a humidifier in places without human activity may make it possible to
      inactivate NV in the dry state on any surface within a contaminated room without
      serious adverse effects.

PMID- 20055220
TI  - Isolation of Pseudomonas aeruginosa from cockroaches Captured in hospitals in
      Japan, and their antibiotic susceptibility.
AB  - Pseudomonas aeruginosa strains were isolated from 45 of 370 (12.2%) cockroaches
      captured in hospitals. By cockroach species, the bacterial strains were isolated
      from 39 of 181 (21.5%) Periplaneta fuliginosa and 6 of 183 (3.3%) Blattella
      germanica, showing a significant difference (p<0.01). Many P. aeruginosa-carrying
      cockroaches inhabited locker rooms (66.7%) and kitchens (17.8%). In terms of
      serotyping, many isolates were typed into groups A, G, and B. In drug sensitivity
      tests, strains showed the highest sensitivity to ciprofloxacin with an MIC90 of
      0.25 microg/ml, followed by 2 microg/ml meropenem, and 4 microg/ml ceftazidime,
      gentamicin, and ofloxacin. In contrast, many strains were resistant to cefotaxime
      and minocycline, accounting for 86.7% of all resistant strains. However, there
      was no multidrug-resistant P. aeruginosa strain, and all strains were negative
      for the metallo-beta-lactamase gene (IMP-1 and VIM-2). These findings suggested
      that cockroach-derived P. aeruginosa may contaminate hospital environments, for
      which the control of disease-carrying insects in hospitals is important.

PMID- 20055221
TI  - Isolation and characterization of novel bisphenol-A--degrading bacteria from
      soils.
AB  - One hundred and seven soil samples were collected from various places in Japan,
      and their bisphenol-A (BPA, 2,2-bis(4-Hydroxyphenyl) propane) degradative
      capacities were evaluated. Eighty-five soil samples possessed BPA degradative
      capacities, and 26 bacterial strains could be isolated as BPA-degrading
      bacterium. Sequence analysis of their 16S rRNA genes indicated that 22 isolates
      belonged to proteobacteria groups, and three of four Gram-positive bacterial
      strains, YA27, NO13, and NO15, were classified as Bacilli. All isolates except
      strain YA27 completely degraded 115 microg/mL BPA in L medium but strain YA27
      degraded only 50 microg/mL BPA. Strain YA27 and three Sphingomonas sp. strains
      could also grow in basal salt media containing BPA as a sole carbon source (BSMB
      medium). In HPLC analyses, some isolates, including the three Sphingomonas
      strains, produced some BPA metabolites in their cultures although the others,
      including strain YA27, produced no detectable metabolite. Furthermore, the
      Pseudomonas strains SU1 and SU4 produced some BPA metabolites that were different
      from the metabolites detected in the degradation of BPA by the S. bisphenolicum
      strain AO1. These results suggested that all isolates could be applicable to the
      bioremediation of BPA-polluted soil and water. Furthermore, we suggest that
      Bacillus sp. YA27 and Pseudomonas SU1 and SU4 may exhibit novel BPA metabolism
      pathways that are distinct from that of S. bisphenolicum AO1.

PMID- 20055222
TI  - Evaluation of the biodegradability of polyurethane and its derivatives by using
      lipase-displaying arming yeast.
AB  - Candida antarctica lipase B (CALB) has been used to polymerize and degrade
      polyesters. We developed a convenient method for investigating the
      biodegradability of plastics that involves the use of CALB-displaying "arming
      yeast." Polyurethane containing dulcitol units was prepared and used as the model
      material. Additionally, standard polyurethane with no dulcitol units was prepared
      by reacting 2,4-toluene diisocyanate with ethylene glycol. These polymers were
      incubated with CALB-displaying yeast cells. The polyurethane containing dulcitol
      was degraded, while the standard polyurethane was relatively unaffected. Arming
      yeast displaying appropriate enzymes can be used to investigate the
      biodegradability of synthetic plastics. It was also revealed that arming yeasts
      were applicable to evaluate the degradation of the film state of polyurethane.

PMID- 20055223
TI  - Fungal growth on anion surfactant medium.
AB  - Before the present study, no fungi using anion surfactant as a nutrient had been
      identified, although some fungi were known to use nonion surfactant. Washing
      water collected from 63 washing machines was inoculated onto 0.1% LAS (Sodium
      dodecyl benzenesulfonate) anion surfactant media to identify fungi that can feed
      on anion-surfactant. Small dark colonies of fungi were found on several of the
      Petri-dishes from 12 days after inoculation. These were identified as
      Cladophialophora boppii and Exophiala spinifera using morphological features and
      rDNA data. A number of the isolates of C. boppii specifically were recognized as
      using anion surfactant as a nutrient. The growth characteristics of the two
      fungal species were examined on surfactant media of three kinds. Apart from anion
      surfactant, the fungi were also able to grow on nonion surfactant and on soap.
      The application of these fungi for environmental cleansing after detergent
      pollution is also discussed.

PMID- 20055224
TI  - Growth in Acanthamoeba sp. and antibiotic susceptibility of Legionella micdadei
      isolated from hot spring water samples.
AB  - As part of an epidemiological study on legionellosis, we attempted to isolate
      Legionella spp. from hot spring water samples, and were able to isolate
      Legionella micdadei from 3 (5.5%) of 55 samples. All of these isolates were able
      to grow within Acanthamoeba sp., suggesting that the isolates will be pathogens.
      We also confirmed that the K-2 strain from hot spring water grew in guinea pig
      monocytes. Sensitivity tests using 10 drugs showed that the isolates were most
      sensitive to imipenem, with the MIC90 of 0.032 microg/ml, were least sensitive to
      minocycline, with the MIC90 of 4 microg/ml, and were not sensitive to low amounts
      of other drugs.

PMID- 20055225
TI  - Insects and illnesses: contributions to the history of medical entomology.
      Introduction.

PMID- 20055226
TI  - History of the early dipteran systematics in Italy: from Lyncei to Battista
      Grassi.
AB  - This presentation starts with Galileo's discovery of the microscope and the first
      Lyncei. Giovanni Heckius and Francesco Stelluti demonstrated different kinds of
      mosquitoes. Later, in Florence, the Academy of Cimento solved the problem of
      mosquito reproduction with the discoveries of Francesco Redi, Pietro Paolo da
      Sangallo, Giuseppe Del Papa and Giovanni Maria Lancisi in the 18th century. In
      19th century Eugenio Ficalbi reviewed the Italian Culicids. Once Battista Grassi
      solved the cycle of Anopheles and Plasmodia, further researches followed by
      Golgi, Celli, Marchiafava, Bastianelli and Bignami, as well as by Roland Ross.

PMID- 20055227
TI  - Knowledge of diptera in France from the beginning to the early twentieth century.
AB  - Although insects have been objects of observation in French-speaking countries
      since the seventeenth century, and were illustrated by Reaumur and other
      scientists during the eighteenth, specialized dipterology only emerged in the
      first half of the nineteenth century. The two main divisions of the Order Diptera
      were defined by French entomologists, namely Nemocera (currently Nematocera) by
      Latreille in 1817, and Brachocera (currently Brachycera) by Macquart in 1834.
      Insects as a whole were rarely studied until the late nineteenth century, when
      the discovery of their role in the transmission of important diseases resulted in
      the creation of a new discipline: medical entomology. From this time on,
      medically important groups (mosquitoes, tsetse flies, etc.) have been objects of
      intense concern and study, especially at the Pasteur Institute and the Paris
      Faculte de medecine. But the most important French dipterist* in the twentieth
      century has probably been the Museum specialist Eugene Seguy.

PMID- 20055228
TI  - Scientific collections, tropical medicine and the development of entomology in
      Brazil: the contribution of Instituto Oswaldo Cruz.
AB  - The entomological collection of the Institute Oswaldo Cruz is one of the most
      representative of neotropical insects, comprising a diverse variety of specimens
      of distinct taxonomic groups, including those not linked to research in tropical
      medicine. The present work retraces the history of the collection and reports on
      its main actors and their professional relationships, emphasizing the peculiarity
      of such an important collection still being housed in a medical research
      institution.

PMID- 20055229
TI  - Battista Grassi entomologist and the Roman School of Malariology.
AB  - Grassi's entomological researches go back to his early years of university study,
      initially being concerned with agriculture pests. After working in Heidelberg,
      Grassi's interests turned to basic problems of entomology, such as the
      evolutionary origin of Miriapoda and Insecta, and termite caste determination.
      His first investigations into medical entomology related to the problem of bird
      malaria, which he studied only in relation to the hematic parasites. In 1895,
      Grassi was appointed Professor of Comparative Anatomy at Rome University, and
      initiated his entomological collaboration with the Roman malariologists, Amico
      Bignami, Giuseppe Bastianelli and Ettore Marchiafava. At the end of 1898, they
      announced, at the session of the Accademia dei Lincei on December 4th, that a
      healthy man in a non-malarial zone had contracted tertian malaria after being
      bitten by an experimentally infected Anopheles claviger. Following his
      disappointment at being excluded from the Nobel prize, Grassi devoted his
      attention to another important insect related to the transmission of parasitic
      disease, the sand fly, Phlebotomus papatasii. After World War I malaria had
      flared up with renewed vigour, so that the social importance of the disease
      convinced Grassi to resume his studies in 1918. The problem he faced in these
      years was "Anophelism without malaria" which was to be solved a year after his
      death by his pupil Falleroni, who demonstrated that there are six cryptic species
      of Anopheles of which only four bite humans and transmit malaria. Battista Grassi
      died on 4 May 1925, working to the end: he was reading the proofs of his last
      paper, Lezione sulla malaria.

PMID- 20055230
TI  - Raphael Blanchard, parasitology, and the positioning of medical entomology in
      Paris.
AB  - The histories of medical entomology and parasitology are entwined. Raphael
      Blanchard (1857-1919), Chair of Medical Natural History and Parasitology at the
      Faculty of Medicine in Paris, organized the teaching of medical entomology and
      civilian colonial medicine. He also founded and edited the journal Archives de
      Parasitologie and started the Institute de Medecine Coloniale where he mentored
      many foreign students and researchers. Additionally, Blanchard is important for
      his scientific internationalism and medical historical work on the cultural
      location of parasitology and for training the future professors of parasitology
      Jules Guiart, Emile Brumpt, and Charles Joyeux.

PMID- 20055231
TI  - The Sergent brothers and the antimalarial campaigns in Algeria (1902-1948).
AB  - Edmond and Etienne Sergent, "the Sergent brothers", were both born in Algeria.
      They both studied medicine at the Algiers Medical School and then followed the
      Course of Microbiology of Emile Roux at the Institut Pasteur in Paris (1899
      1900). From 1900, they were put in charge of a permanent mission aimed at
      antimalarial control in Algeria, which was supervised by the Institut Pasteur.
      The first campaign was carried out during the summer of 1902 at a station of the
      East Algerian Railway Company. The success of this mission lead to the creation
      of the Antimalaric Department of Algeria in 1904, which was directed by Etienne
      Sergent for the duration his life. This antimalarial programme was progressively
      extended to many other locations. The programme was optimized between 1927 and
      1947, in the experimental field study of the Ouled Mendil Marsh, where global
      environmental measures and drainage lead to settlement of farms, the families of
      which did not suffered from malaria. At a time when neither insecticides nor
      synthetic antimalarial drug existed, antimalarial control measures that were
      developed tended to target human reservoirs and the mosquito vectors. The
      extension of the programme across the Algerian territory lead to a decrease of
      both malaria endemicity and extension of affected areas.

PMID- 20055232
TI  - The discovery of the vector of Robles disease.
AB  - The origin and transmission of African filariasis has long remained enigmatic.
      Between 1915 and 1917, the pathogenic role of Onchocerca volvulus and its
      transmission by insects of the genus Simulium, had been established in Guatemala
      by Rodolfo Robles who took opportunity of a series of discoveries to formulate
      his hypothesis on the origin of Latin Americna Onchocerchiasis. The present paper
      gives an historical account of the steps and the context having led to the
      formulation of the aetiological hypothesis and the relevant vector
      identification.

PMID- 20055233
TI  - Medical and agricultural entomology in Brazil: a historical approach.
AB  - Medical Entomology emerged in Brazil in the late nineteenth century, through the
      initiative of a group of physicians dedicated to researching microorganisms
      related to diseases of public health importance, especially yellow fever and
      malaria. They led the institutionalization of Bacteriology and Tropical Medicine
      in southeast Brazil and the sanitation of coastal cities and, subsequently, rural
      areas. Medical Entomology provided the professionals who would undertake
      campaigns against agricultural plagues, as well as the institutionalization of
      Agronomy and Veterinary Medicine. In the present article, I intend to show how
      relations between the professionals who gave life to Medical Entomology in Brazil
      were interwoven and to illustrate their relations with entomologists in other
      countries. I will also present an overview of the research problems faced by
      Brazilian entomologists at the turn of the nineteenth century and early decades
      of the twentieth.

PMID- 20055234
TI  - Culicoides and the Tartar Steppe: Il Deserto dei Tartari Culicoides and the
      spread of blue tongue virus.
AB  - Culicoides were described for the first time in England in 1713, but named by
      Latreille in 1809 only. Even so, they were better known as Ceratopogon until
      Kieffer reintroduced the name Culicoides. The family name became Ceratopogonidae,
      the description by Meigen (1803) being better adapted to that systematic level.
      Culicoides were considered simply as biting insects until it was found that they
      can carry filaria and viruses. In 1944, du Toit in Transvaal described their role
      in the transmission of blue-tongue virus. Blue-tongue disease has since extended
      progressively northward from South Africa, disseminated by Culicoides imicola. At
      the end of the 20th century, it reached the southern shores of the Mediterranean
      sea, and has since threatened the southern Europe. Surveillance and prevention
      procedures were put in place, but fortress Europe was taken breached when a
      different strain of the virus entered through Belgium in 2006. Transmitted by
      local Culicoides species that were aggressive and abundant, the disease spread
      quickly, in a disastrous epizootic southward through more than half of France.
      Westward, infected insects have been carried by wind over the Channel,
      introducing the disease to England.

PMID- 20055235
TI  - Reconstructing an epistemological itinerary: environmental theories of variation
      in Roubaud's experiments on Glossina flies and Anopheles, 1900-1938.
AB  - This paper addresses the theories and debates concerning the influence of
      environment on vectors and species variation. In particular, it focuses on
      theories about how climate and domesticated animals affected vectors that
      transmitted sleeping sickness and malaria. Emile Roubaud (1882-1962), a
      Pasteurian entomologist, worked on the adaptation and variation of Glossina fly
      races in order to elaborate environmental interventions for sleeping sickness
      campaigns in Africa. He then developed the theory concerning Glossina flies'
      biting preferences for livestock, and the implications of such preferences for
      human protection against sleeping sickness transmission. Subsequently, he
      extended this theory about insect biting preferences to malaria in Europe. He
      thus used one disease model, the sleeping sickness complex, and extended it to
      another, the malaria complex. He subsequently became interested into zoophilic
      races of Anopheles maculipennis and advocated the hypothesis that the zoophilic
      Anophelines' maxillary index was a decisive feature in malaria transmission, for
      it could help preventing humans from the bite of the Anopheles vector. The paper
      also analyzes how these theories were received and debated at the time of their
      publication in scientific journals and proceedings.

PMID- 20055236
TI  - Theories of genetics and evolution and the development of medical entomology in
      France (1900-1939).
AB  - The development of entomology and medical entomology in France is discussed in
      the context of the prevalence of Lamarckian ideas concerning heredity and
      evolution. Lamarckian ideas have greatly influenced research carried out at the
      Institut Pasteur by Emile Roubaud and more generally in Felix Mesnil's
      laboratory, as well as research in general entomology at the Museum national
      d'histoire naturelle. By contrast, it did not influence research and teaching at
      the Faculte de medecine of Paris or that of physicians more generally including
      those in overseas Instituts Pasteur, which clearly kept away from theoretical
      discussion concerning the origin of variations and adaptation in insects of
      medical interest.

PMID- 20055237
TI  - Entomology in translation: interpreting French medical entomological knowledge in
      colonial Mali.
AB  - This essay examines how knowledge and practices around entomology and
      parasitology travelled and the consequences of their mobility. In exploring three
      anti-malaria campaigns in French Soudan before 1960, it argues that the history
      of medical entomology's travels entailed multiple temporal, spatial, social
      translations that African medical personnel, intellectuals, healers, and farmers
      in French Soudan reinterpreted, appropriated, and sometimes wholly rejected. This
      essay also focuses on "erroneous" translations, detailing how and why middle
      class medical personnel and intellectuals interpreted and reformulated farmers'
      and healers' diagnostic categories that may or may not be malaria. Anti-mosquito
      and antilarval interventions, and more generally anti-malaria interventions,
      influenced how African colonial subjects and health workers understood certain
      vectors and of certain maladies. These understandings, in turn, shaped the
      consequences of subsequent public health measures. Histories of translated
      parasitological and entomological knowledge and etiologies of illness have
      critical implications for contemporary malaria control efforts: interventions to
      reduce malaria transmission through various kinds of entomological controls that
      require active participation of local populations cannot be effective if all
      participants cannot agree upon what is being controlled or prevented.

PMID- 20055238
TI  - Science and popular participation in the investigation of heartwater in South
      Africa, c. 1870-1950.
AB  - During the late nineteenth century, settler farmers in southern Africa identified
      heartwater as a damaging disease of small stock and cattle. They advanced various
      explanations of the disease, including the theory that it was caused by the bite
      of ticks. Around 1900, the American entomologist C.P. Lousbury demonstrated that
      heartwater was transmitted by the bont tick. He also worked out the life cycle
      and life habits of the tick. Subsequently, farmers developed methods of
      controlling ticks by dipping animals in solutions of arsenic. By 1910, the
      practice of dipping cattle had become very widespread over much of southern
      Africa. The expansion of the practice was greatly stimulated by the coming of the
      deadly tick-borne disease, East Coast fever. At this time, veterinary scientists
      attempted to develop a vaccine against heartwater, but with little success.
      Little further progress was made until the 1920s, when the American scientist
      E.V. Cowdry identified a causal agent, Rickettsia ruminantium, while on a
      research secondment to South Africa. By the 1940s, South African veterinary
      scientists had devised methods of immunising stock against heartwater, but there
      remained considerable technical difficulties and their use remained limited.
      Dipping in arsenic solutions to attack the tick on the animal thus remained the
      most important means of controlling disease in the first half of the twentieth
      century.

PMID- 20055239
TI  - Veterinary entomology, colonial science and the challenge of tick-borne diseases
      in South Africa during the late nineteenth and early twentieth centuries.
AB  - This article provides an historical overview of developments in veterinary
      entomology during the late nineteenth and early twentieth centuries. During that
      period state employed entomologists and veterinary scientists discovered that
      ticks were responsible for transmitting a number of livestock diseases in South
      Africa. Diseases such as heartwater, redwater and gallsickness were endemic to
      the country. They had a detrimental effect on pastoral output, which was a
      mainstay of the national economy. Then in 1902 the decimating cattle disease East
      Coast fever arrived making the search for cures or preventatives all the more
      urgent. Vaccine technologies against tick-borne diseases remained elusive overall
      and on the basis of scientific knowledge, the South African state recommended
      regularly dipping animals in chemical solutions to destroy the ticks. Dipping
      along with quarantines and culls resulted in the eradication of East Coast fever
      from South Africa in the early 1950s. However, from the 1930s some ticks evolved
      a resistance to the chemical dips meaning that diseases like redwater were
      unlikely to be eliminated by that means. Scientists toiled to improve upon
      existing dipping technologies and also carried out ecological surveys to enhance
      their ability to predict outbreaks. Over the longer term dipping was not a
      panacea and ticks continue to present a major challenge to pastoral farming.

PMID- 20055240
TI  - Sowing the seeds of economic entomology: houseflies and the emergence of medical
      entomology in Britain.
AB  - The golden age of medical entomology, 1870-1920, is often celebrated for the
      elucidation of the aetiology of vector-borne diseases within the rubric of the
      emergent discipline of tropical medicine. Within these triumphal accounts, the
      origins of vector control science and technology remain curiously underexplored;
      yet vector control and eradication constituted the basis of the entomologists'
      expertise within the emergent specialism of medical entomology. New imperial
      historians have been sensitive to the ideological implications of vector control
      policies in the colonies and protectorates, but the reciprocal transfer of vector
      control knowledge, practices and policies between periphery and core have
      received little attention. This paper argues that medical entomology arose in
      Britain as an amalgam of tropical medicine and agricultural entomology under the
      umbrella of "economic entomology". An examination of early twentieth-century anti
      housefly campaigns sheds light on the relative importance of medical entomology
      as an imperial science for the careers, practices, and policies of economic
      entomologists working in Britain. Moreover, their sensitivity to vector ecology
      provides insight into late nineteenth- and early twentieth-century urban
      environments and environmental conditions of front-line war.

PMID- 20055241
TI  - 15th anniversary of University Department of Neurology, Sestre Milosrdnice
      University Hospital. 70th anniversary of Department of Neurology and Psychiatry.

PMID- 20055242
TI  - Assessment of subtle cognitive impairment in stroke-free patients with carotid
      disease.
AB  - Carotid disease is a known risk factor for stroke and stroke is a known risk
      factor for cognitive impairment, but relation between carotid artery stenosis and
      cognitive function in asymptomatic individuals is less clear. Most patients have
      only minor complaints of cognitive dysfunction and assessment with usual tests is
      not sensitive enough. The study included 26 stroke-free patients (15 male and 11
      female), mean age 66.3 +/- 8.7 years, with advanced internal carotid artery
      stenosis or/and occlusion (ICAs/o). Left ICAs/o was present in 11, right ICAs/o
      in eight, and bilateral ICAs/o in seven patients. History was taken and
      assessment of risk factors, brain CT scan and neurologic examination were
      performed. Cognitive functions were tested by use of Mini Mental State
      Examination (MMSE) and Montreal Cognitive Assessment (MoCA). All patients were
      asymptomatic, except for two patients that presented with repeated transient
      ischemic attack (TIA). In all subjects median MMSE scores were within the normal
      range (27.5; IQ range 25-29), while mean MoCA scores were abnormal (22.6 +/-
      3.4). Patients with left ICAs/o scored slightly better on MoCA (22.9 +/- 3.3)
      than patients with right ICAs/o (22.4 +/- 4.0). Delayed recall MoCA subtest was
      impaired in 22/26 patients and visuospatial subtest in 23/26 patients; however,
      there was no statistically significant difference according to the side of
      ICAs/o. Patients with the presence of one or two risk factors scored lower on
      visuospatial/executive MoCA subtests (P = 0.018) as compared with patients with
      multiple risk factors. MoCA proved to be a sensitive tool for assessment of mild
      cognitive changes in stroke-free patients with advanced ICAs/o. Decline was most
      pronounced in visuospatial, executive and short-memory functions.

PMID- 20055243
TI  - The contralateral carotid disease in patients with internal carotid artery
      occlusion.
AB  - The one-year incidence of carotid occlusion is 6/100 000 inhabitants in general
      population. Stroke incidence and mortality rate in these patients vary. Patients
      that underwent carotid endarterectomy (CES) are at a higher risk of progression
      of contralateral carotid stenosis. The aim of the study was to investigate the
      management and natural history of the contralateral internal carotid artery
      disease in patients with internal carotid artery occlusion (ICAO). During one
      year, 297 patients with ICAO were investigated. Follow up examinations were
      retrospectively analyzed and patients were divided into groups according to
      contralateral carotid disease. Out of 297 patients, only one investigation was
      performed in 90 patients with carotid occlusion. Thirty three patients were
      followed up due to postoperative ICAO. In 14 patients, ICAO developed during
      ultrasonographic follow up. In this group of patients, 9 had unchanged
      contralateral findings, whereas in 5 patients disease progression was observed.
      Out of 44 patients with ICAO and contralateral subtotal stenosis at initial
      investigation, 42 underwent carotid surgery. Postoperatively, 32 patients had
      normal findings, 6 developed mild carotid stenosis, 2 developed moderate carotid
      stenosis, and 2 had postoperative carotid occlusion. Two patients were followed
      up without intervention. Nine patients with bilateral ICAO were followed-up for
      years. Follow up was continued in 106 patients with ICAO and contralateral mild
      to moderate changes. The finding was unchanged in 68 patients. In 21 (30%)
      patients the disease progressed to subtotal stenosis and 18 patients underwent
      carotid surgery. Accordingly, contralateral carotid disease progression was
      observed in one third of patients with carotid occlusion. Additional studies on
      the issue are needed.

PMID- 20055244
TI  - Development of postoperative internal carotid artery occlusion due to the
      presence of risk factors.
AB  - Postoperative internal carotid artery (ICA) occlusion is a rare condition with
      few data on the risk factors. The aim of the study was to analyze risk factors
      and ischemic symptomatology in patients with postoperative ICA occlusion. During
      one year period, 33 patients with postoperative ICA occlusion were examined at
      Cerebrovascular Laboratory. Medical history, clinical findings and
      atherosclerosis risk factors were compared with data on 33 patients with
      satisfactory postoperative finding. Student's t-test was used on data comparison
      (P < 0.05). In 31 of 33 patients, ICA occlusion was recorded on the first
      postoperative examination, 3 months after carotid endarterectomy (18 right and 15
      left). In 8 patients, combined occlusion of the common carotid artery and ICA was
      found (4 right, 4 left). One patient ICA developed occlusion during the first and
      third postoperative year each. Clinically, three patients presented with ischemic
      symptoms (one stroke and two transitory ischemic attacks (TIA)). The following
      risk factors were present in the group with postoperative ICA occlusion:
      hypertension in 18, smoking in 10, hyperlipidemia in 8, diabetes mellitus in 9,
      history of stroke in 13, TIA in 3, heart attack in 4 and coronary disease in 3
      patients; the respective figures in the control group were as follows: 25, 11,
      16, 7, 7, 3, 4 and 3. There was no significant between-group difference in the
      presence of risk factors. Study results suggested that postoperative ICA
      occlusion was not caused by atherosclerosis risk factors but by perioperative
      complications.

PMID- 20055245
TI  - Beta stiffness--setting age standards.
AB  - Beta stiffness index is one of the most commonly used measures of depicting
      mechanical arterial properties and development of preclinical atherosclerosis.
      Main influences on its value hold age and blood pressure levels. The goal of this
      study was to determine age standards of beta stiffness index on common carotid
      artery in our population using a formula modified by Kawasaki. The study was
      conducted in 150 healthy volunteers aged 25-75 on an Aloka 5500-SSD Pro-sound
      ultrasound platform using B and M modes. The data obtained were analyzed by
      appropriate statistical methods. Study results confirmed linear relationship of
      beta index and age. Calculation of beta index is applicable for assessment and
      monitoring of vascular physiology changes because it is simple for use, prompt in
      analysis and suitable for bed-side evaluation.

PMID- 20055246
TI  - Serum HDL, LDL and total cholesterol in patients with late-life onset of
      Alzheimer's disease versus vascular dementia.
AB  - Patients with cerebrovascular risk factors are nowadays recognized as being at an
      increased risk of developing cognitive decline of both types. In this pilot
      study, we evaluated the levels of cholesterol (total, HDL, LDL) in patients with
      both vascular dementia (VD) and Alzheimer's type of dementia (AD). Cognitive
      decline was assessed using Mini Mental State Examination (MMSE) as a standardized
      method. The study included 66 patients diagnosed with dementia. AD was diagnosed
      in 43 patients (22 male and 21 female) mean age (+/- SD) 72.79 +/- 8.19 years and
      VD in 23 patients (mean age +/- SD, 77.43 +/- 7.58 years). In AD group, 18
      patients had cholesterol values within the normal range, whereas 25 patients had
      elevated levels of cholesterol. The mean value of total plasma cholesterol was
      5.39 (SD = 1.05), LDL cholesterol 3.33 (SD = 0.95) and HDL cholesterol 1.41 (SD =
      0.34). In VD group, 11 patients had cholesterol values within the normal range,
      whereas 12 patients had elevated levels of cholesterol. In this group, the mean
      value of total plasma cholesterol was 5.78 (SD = 1.06), HDL cholesterol 1.44 (SD
      = 0.57) and LDL cholesterol 3.72 (SD = 0.85). Total cholesterol, LDL cholesterol
      and HDL cholesterol levels were higher in the group of patients with VD, however,
      the difference was not statistically significant.

PMID- 20055247
TI  - Median nerve imaging using high-resolution ultrasound in healthy subjects.
AB  - Although electroneuro- and electromyography are still the leading diagnostic
      methods for investigation of peripheral nerve function, they do not provide
      information on their morphology. This study was conducted to evaluate the
      suitability of ultrasonography in visualization of median nerve in healthy
      volunteers. Twenty-five asymptomatic volunteers (17 women and 8 men), age range
      21-47 years, participated in the study. Body height was measured and handedness
      ascertained, as well as average time spent daily working on a computer. The
      device used was Aloka Prosound Alpha10 Premier with a 13-MHz probe, using custom
      preset for musculoskeletal sonography. The following dimensions of median nerve
      at the pisiform bone level were measured bilaterally: cross-sectional area (CSA),
      circumference, and longer and shorter diameter. Using the latter values, the
      flattening ratio (FR) was calculated. Median nerve and the surrounding soft
      tissue structures were easily depicted in all study subjects. The mean median
      nerve CSA was 9.70 mm2 (range 5-15 mm2, SD 2.25 mm2), mean FR (longer/shorter
      diameter) 4.04 (range 2.16-6.08), and median height 172.72 cm. Only one subject
      was left-handed. The mean time spent daily working on a computer (overall mean of
      3.2 h/day) did not correlate with either CSA or FR for the dominant hand. In four
      subjects, an aberrant artery accompanying median nerve was visualized. High
      resolution sonographic imaging is a fast and noninvasive method for assessment of
      various morphological properties of median nerve and can be used to enhance
      diagnostic efficiency.

PMID- 20055248
TI  - Prospective surveillance of Croatian pregnant women on lamotrigine monotherapy-
      aspects of pre-pregnancy counseling and drug monitoring.
AB  - We prospectively surveyed 23 pregnant women with epilepsy on lamotrigine
      monotherapy and reported outcome of their pregnancies, including one fetal
      intrauterine death, one spontaneous abortion and two preterm deliveries. There
      were no congenital malformations in their offspring. Women with pregnancy
      planning and folic acid intake delivered babies with higher values of birth
      weight and birth length. There was large inter-patient variation during drug
      monitoring and in the need of dose adjustment. Individual approach to every woman
      and monotherapy with minimal effective lamotrigine dose with frequent drug
      monitoring enhances the possibility for successful pregnancy. The management of
      women with epilepsy should begin with pre-pregnancy counseling. Planned pregnancy
      enables periconceptional folic acid supplementation. Despite the small number of
      cases, these data indicate that la motrigine treatment during pregnancy might be
      relatively safe. Larger prospective studies are needed to obtain adequate power
      for statistical analysis including long-term cohort studies.

PMID- 20055249
TI  - Emergency EEG and diagnostic yield.
AB  - The aim of the study was to determine whether an acute loss of consciousness,
      mental status change or related symptoms correlated with the presence of
      epileptiform abnormalities on urgent EEG. We analyzed 228 consecutive patients
      admitted to Emergency Room during the past 12 months and referred for urgent EEG
      evaluation. All patients had either a brief loss of consciousness or acute brain
      disorder, with a clinical diagnosis of epilepsy, syncope, head trauma, headache,
      transient ischemic attack (TIA) or vertigo. Statistical analysis was performed
      using Spearman's rho test for group comparison and multivariate regression
      analysis. The mean age of patients was 48 +/- 20 years. The frequency of
      referring clinical diagnoses was as follows: epilepsy 44.7% (102/228), TIA 15.8%
      (36/228), syncope 15.4% (35/228), headache 11% (25/228), vertigo 7.9% (18/228)
      and acute head trauma 5.3% (12/228). EEG indicated epileptiform abnormalities in
      14.9% (34/228) and focal slowing in 9.2% (21/228) of patients. The majority of
      them (26%; 21/81) had a clinical diagnosis of epilepsy. There was a significant
      correlation between clinical diagnosis of epilepsy and epileptiform EEG
      (Spearman's rho = 0.13; P < 0.04). Multivariate regression analysis showed that
      there was no predictive value in the clinical diagnosis of epilepsy and
      epileptiform EEG (beta = 1.483, P = 0.16). In conclusion, epilepsy was the most
      common clinical diagnosis in patients referred for urgent EEG. There was a
      significant correlation between the diagnosis and specific EEG abnormalities,
      however, the diagnosis of epilepsy failed to predict epileptiform activity on
      EEG. Study results suggested urgent EEG to have a high yield in patients with
      epilepsy.

PMID- 20055250
TI  - Thrombolysis for acute ischemic stroke--our experiences as part of SITS-MOST.
AB  - Thrombolysis with intravenous recombinant tissue plasminogen activator (rtPA) is
      the first evidence based treatment for acute ischemic stroke, which aims to
      reduce the cerebrovascular lesion. At University Department of Neurology, Sestre
      milosrdnice University Hospital, Zagreb, thrombolytic therapy with intravenous
      rtPA (alteplase) (Actilyse) for acute ischemic stroke was introduced in 2004. We
      present our results referring to demographic, time logistics and clinical outcome
      data as part of SITS-MOST (Safe Implementation of Thrombolysis in Stroke -
      MOnitoring STudy) and compare them with the results from other centers in Croatia
      and all other participating centers. Up to now, 56 patients (61% of male and 39%
      of female, average age 67 years) have been treated at our department with
      intravenous rt-PA (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose
      given as a bolus followed by 60-minute infusion. Our experiences with
      thrombolytic therapy with intravenous rt-PA (alteplase) (Actilyse) for acute
      ischemic stroke confirm the safety and the efficacy of this therapy.

PMID- 20055251
TI  - The association of obesity and cerebrovascular disease in young adults--a pilot
      study.
AB  - Obesity has been recognized as an isolated risk factor for stroke. In obese
      patients, other risk factors for stroke such as hypertension, hyperlipidemia,
      ischemic heart disease and obstructive sleep apnea are more frequently present.
      The aim of this study was to assess the presence of obesity among other risk
      factors for stroke in younger adult patients with ischemic stroke. It was a pilot
      study performed in ischemic stroke patients aged 18-55. In addition to the
      routine diagnostic work-up, body height, weight and waist circumference were
      measured in study patients. The study included 50 patients, 23 female and 27
      male. The mean age of male patients was 39.8 +/- 10.5 and of female patients 41.6
      +/- 7.7 years. In control group The mean waist circumference was 94.9 +/- 5.8 cm
      in the control group and 102.6 +/- 9.8 cm in the male stroke group. There was no
      significant difference in waist circumference between the control and patient
      female groups and in body mass index among all groups. In younger males, waist
      circumference could be considered as an important risk factor for stroke.

PMID- 20055252
TI  - Assessment of breath holding index during orthostasis.
AB  - The aim of the study was to assess differences in cerebrovascular reactivity in
      healthy subjects during orthostasis. Twenty healthy volunteers (11 men and 9
      women) with no atherosclerotic risk factors were evaluated by use of transcranial
      Doppler. The breath holding index (BHI) was obtained in supine and upright
      posture using standardized procedure. Student's t-test was used on comparison of
      the mean blood flow velocities (MBFV) and BHI between supine and upright posture
      and between the left and right side of the body. The middle cerebral artery MBFV
      in supine posture was 66.6 cm/s on the right side and 68.5 cm/s on the left side
      and in upright posture 60.6 cm/s on the right side and 62.3 cm/s on the left
      side. There was no significant MBFV difference either between supine and upright
      posture or between male and female subjects. The mean BHI in supine posture was
      1.59 on the right side, 1.65 on the left side, and in upright posture 1.63 on the
      right side and 1.7 on the left side, without significant sex difference. There
      was no statistically significant differences in BHI between supine and upright
      posture (P = 0.81 and P = 0.68 for the right and left side, respectively) or
      between the two sides of the body in supine (P = 0.71) and upright posture (P =
      0.8). In conclusion, evaluation of cerebrovascular reactivity yielded no
      significant difference in BHI values during orthostatic stress.

PMID- 20055253
TI  - Blood flow velocity in middle cerebral artery during visuo-motor tasks using a
      mirror: a transcranial Doppler study.
AB  - Mirror illusion means that standing in front of a mirror placed in sagittal
      plane, with the head tilted on one side and one arm stretched forward, one side
      of the body is reflected as if it were the other side by mirror visual feedback.
      The aim of this study was to monitor blood flow changes in middle cerebral artery
      (MCA) by use of transcranial Doppler (TCD) in individuals during motor tasks and
      tasks using mirror visual feedback. Eight young healthy volunteers (four male and
      four female) were included in the study. TCD recording in MCA was done during
      each task consisting of various motor and visuomotor activities using mirror
      illusion. Both MCA mean blow flow velocity (MBFV) was measured while the subjects
      were seated in a comfortable chair. The MCA MBFV recordings are presented as
      baseline values. During the illusion of motor hand activation, when the subject
      was making right hand flexions and watching its reflection in the mirror, with
      the left hand immobile, an increase was observed the contralateral MCA MBFV (task
      3, +4.5% baseline value; P = 0.017). Furthermore, when the subject made left hand
      flexions while watching the reflection of the immobile right hand in the mirror,
      there was an increase in the right MCA MBFV (+5.6% baseline value; P = 0.044),
      which was more pronounced than during the illusion of motor hand activation (task
      3) and less than during direct vision of hand flexion (task 2, +6.3% baseline
      value; P = 0.005). Our data showed that visual illusion of action, as well as
      direct action observation could increase the MCA MBFV, which brings forward the
      possible usage of mirror illusion as a tool in motor neurorehabilitation.

PMID- 20055254
TI  - Gabapentin in the prophylaxis of cluster headache: an observational open label
      study.
AB  - Cluster headache is an extremely painful syndrome that occurs more frequently in
      men. Although periodic in most cases, cluster headache has a considerable impact
      on the patient quality of life. Acute therapy is usually not sufficient and most
      patients warrant prophylactic treatment. The aim of this study was to evaluate
      the efficacy and safety of gabapentin as prophylaxis in patients with cluster
      headache previously successfully or unsuccessfully treated with other
      prophylactic medications. The study included 14 patients, 9 men and 5 women (mean
      age 42 +/- 15 years). Gabapentin was gradually introduced; the maintenance dose
      was in the range from 900 mg to 2400 mg: 900 mg/day in 6, 1200 mg/day in 2, 1800
      mg/day in 4 and 2400 mg/day in 2 patients. The mean duration of treatment was 3.5
      (range 2-5) months. Within 1-2 weeks, patients reported response to treatment.
      The mean number of headache days/4 weeks was reduced from 378 (mean 27) at
      baseline to 210 (mean 15) at the end of follow up, yielding a reduction by 12
      headache days/4 weeks or by 44.94% in headache frequency. Pain intensity was
      decreased by 25% in 1 (7.14%) patient, by 50% in 8 (57.14%) and by 75% in 3
      (21.4%) patients, whereas 2 (14.28%) patients were non-responders. Upon
      completion of gabapentin therapy, there were no recurrent in treated patients.
      Adverse events were reported in 8/14 (57.14%) patients and were generally of mild
      to moderate severity. The most frequently reported adverse events were
      drowsiness, dizziness, slowness and constipation. There were no drop-outs due to
      adverse events.

PMID- 20055255
TI  - Felix Mendelssohn Bartholdy (1809-1847)--Goethe's favorite.
AB  - Felix Mendelssohn, Goethe's favorite, who revealed the genius ofJohann Sebastian
      Bach after almost a century of oblivion, was of a fragile constitution. Last year
      of his life he was very depressed because of his sister Fanny's sudden death. The
      last month he had several attacks of severe headaches with agitation, anxiety,
      confusion and slow pulse. Last three days these episodes became more frequent and
      his overall health worsened. After stupor and coma, he died from probable
      subarachnoid (or cerebral) hemorrhage (with hypertension?), like his sister
      several months before.

PMID- 20055256
TI  - Increased donor rate at Sestre milosrdnice University Hospital.
AB  - The rate of organ donation reflects the level of the respective society and
      country development. In Croatia, attempts have been made to increase this rate.
      As a consequence, the number of potential donors with confirmed brain death was
      observed to have steadily increased during the 2004-2008 period. Data on all
      potential donors where the confirmation procedure for brain death was completed
      were retrieved and analyzed. The percentage of donors out of all persons
      diagnosed with brain death and all deaths recorded at the Central Intensive Care
      Unit and at all Hospital departments was calculated. The mean number or organs
      per donor was also calculated. During the 2004-2008 period, the number of donors
      perbrain death persons was 5/unknown, 6/10, 8/13, 11/13 and 18/20; mean age 51,
      50, 39, 48 and 44; donor rate per Central Intensive Care Unit deaths 5.9%, 5.6%,
      5.8%, 10.4% and 12.1%; donor rate per all hospital deaths 0.4%, 0.5%, 0.5%, 1.5%
      and 1.9%; and number of organs per donor 1.6, 2.4, 2.6, 3.0 and 2.7,
      respectively. Study results showed a steady increase in the number of donors and
      organs per donor at Sestre milosrdnice University Hospital during the 2004-2008
      period. More intensive education should be organized at medical schools and for
      medical professionals to identify brain death persons and potential donors. In
      addition, mass media campaigns should improve public awareness and perception of
      the issue.

PMID- 20055257
TI  - Acute cerebrovascular incident caused by septic emboli: a case report.
AB  - Septic embolism is a rare disorder associated with infective endocarditis,
      urinary tract infections, bone infections, femoral thrombophlebitis and
      sinusitis. We present a 53-year-old patient with multiple systemic embolism and
      cerebral infarction resulting from aortal thrombus after surgical treatment of
      the right fibular malleolar fracture with osteosynthetic material placement.
      After the surgery, the patient became antisocial, with decreased appetite and
      substantial weight loss. Computerized tomography scan showed several small
      hypodense zones in the supratentorial and periventricular region of the brain as
      well as bilateral pleural effusion, large infarcts of the spleen and right
      kidney, smaller infarcts of the lower pole of the right kidney, discontinuity of
      the wall of the thoraco-abdominal aorta and a thrombus present in the distal part
      of abdominal aorta. The findings primarily indicated septic emboli. The right
      ankle x-ray showed still present postoperative fracture gap of the right fibular
      malleolus with reduced bone mineralization but no signs of bone destruction.
      Control MSCT of the abdomen showed a large spleen abscess of 10x6 cm in size. Due
      to edema of the right ankle, ultrasonography was performed to reveal a thick
      content in the joint. The patient was transferred to University Department of
      Surgery, where splenectomy with evacuation of the perisplenic abscess together
      with extraction of the osteosynthetic material of the right fibular malleolus was
      performed. If not promptly diagnosed, septic emboli can cause devastating
      neurologic damage. In our patient, early diagnosis and intensive physical therapy
      facilitated almost complete regression of his neurologic deficit.

PMID- 20055258
TI  - Post-stroke depression.
AB  - Depression following a stroke, also referred to as post-stroke depression (PSD),
      has long been recognized as one of the most common complications of stroke. PSD
      has significant adverse consequences on the recovery of motor and cognitive
      deficits, as well as on the risk of mortality associated with stroke. The
      prevalence of PSD varies over time with an apparent peak 3-6 months after stroke
      and subsequent decline reaching about 50% of the initial rates at one year. The
      natural course of major depression after stroke has spontaneous remission
      typically 1 to 2 years after stroke. However, it has also been observed that
      depression becomes chronic and may persist for more than 3 years following
      stroke. On the other hand, minor depression appears to be more variable, with
      both short-term and long-term depression occurring in these patients. Early
      recognition of PSD symptoms and introduction of pharmacological treatment is of
      great importance in the reduction of stroke complications and stroke mortality as
      well as for better functional outcome.

PMID- 20055259
TI  - Possibilities for rehabilitation after stroke.
AB  - The patient's own attitude, activity and social interaction influence functional
      outcome and quality of life after stroke. Rehabilitation of stroke patients
      should start as soon as the patient is in a medically stable condition. The
      concept of early rehabilitation should be provided by an interdisciplinary team,
      preferably in stroke units. The key of successful rehabilitation is teamwork of
      the specialist, patient and patient's family. Stroke, within the fixed limits of
      the brain vascular architecture, is a privileged field of research for the brain
      mind correlations and the mechanisms of brain plasticity. Future studies may
      investigate aspects of cognitive recovery after stroke in individual patients and
      will relate them to the aspects of brain plasticity where synapses are sprouting.
      With this in mind, research will tend to elucidate whether cortical maps are
      enlarging, whether homologous or non-homologous areas are activated, in which
      hemisphere the lesions do occur, whether they are integrated into cognitive and
      behavioral models of recovery and if so, should this clarify the restoration or
      compensation of the normal functions of the brain.

PMID- 20055260
TI  - Stroke unit--where all stroke patients should be treated.
AB  - Acute stroke is one of the leading causes of morbidity and mortality worldwide,
      and as the most important cause of morbidity and long-term disability imposes an
      enormous economic burden. Stroke units (SU) are an effective option to fight
      stroke. According to the European Stroke Organization, SU should provide
      coordinated multidisciplinary care provided by medical personnel specialized in
      stroke care. Helsingborg declaration from 1995 urged for organized management of
      acute stroke in order to reduce mortality below 20% (SU for all stroke patients)
      and to achieve independency in more than 70% of 3-month stroke survivors. At the
      beginning of 2001, the first Croatian SU was established at Sestre milosrdnice
      University Hospital in Zagreb as a hospital ward with dedicated multidisciplinary
      stroke team consisting of neurologists specialized in the management of
      cerebrovascular disease, trained nurses and rehabilitation personnel, together
      with other professionals to enable treatment of stroke patients according to
      current guidelines.

PMID- 20055261
TI  - Differential diagnosis and diagnostic algorithm of demyelinating diseases.
AB  - Demyelinating diseases of the central nervous system include a wide spectrum of
      different disorders that may resemble multiple sclerosis (MS). The diagnosis of
      MS is based on typical clinical and paraclinical criteria. The simplified
      McDonald's criteria, which combine clinical picture, NMR findings, CSF analysis
      and visual evoked potentials, are appropriate for daily neurologic routine. If
      some of these criteria are atypical, diagnostic algorithm should be extended to
      some other procedures to exclude other diseases that can mimic MS not only in
      symptoms, signs or course of the disease but also in laboratory findings. In such
      a case, an alternative, better explanation for the clinical manifestations should
      be considered and performing specific tests is helpful to exclude alternative
      diagnoses.

PMID- 20055262
TI  - Treatment of multiple sclerosis.
AB  - Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the
      central nervous system, characterized by multifocal inflammatory destruction of
      myelin, axonal damage and loss of oligodendrocytes. The disease is carried
      through two stages: inflammatory and degenerative. The most common form of
      disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The
      treatment of MS is devided into: treatment of the acute phase of illness,
      prevention of new relapses and disease progression, and symptomatic treatment.
      Most of the changes in treatment of multiple sclerosis and most of the news in
      recent years concerning new drugs are used in the treatment of progression of the
      disease and prevention of disease relapses. Some of these drugs are registrated
      in most Europian countries and USA, and others are in various stages of research.

PMID- 20055263
TI  - Pineal gland cysts--an overview.
AB  - Pineal cysts occur in all ages, predominantly in adults in the fourth decade of
      life. In series of magnetic resonance imaging (MRI) studies, the prevalence of
      pineal cysts ranged between 1.3% and 4.3% of patients examined for various
      neurologic reasons and up to 10.8% of asymptomatic healthy volunteers. The
      diagnosis of pineal cyst is usually established by MRI with defined radiological
      criteria to distinguish benign pineal cyst from tumors of this area. A recent
      study demonstrated the findings obtained by transcranial sonography to correspond
      to those obtained by MRI in the detection of both pineal gland cyst and pineal
      gland itself, and could be used in the future mainly as follow up examination.
      Pineal cysts usually have no clinical implications and remain asymptomatic for
      years. The most common symptoms include headache, vertigo, visual and oculomotor
      disturbances, and obstructive hydrocephalus. Less frequently, patients present
      with ataxia, motor and sensory impairment, mental and emotional disturbances,
      epilepsy, circadian rhythm disturbances, hypothalamic dysfunction of precocious
      puberty, and recently described occurrence of secondary parkinsonism. Symptomatic
      cysts vary in size from 7 mm to 45 mm, whereas asymptomatic cysts are usually
      less than 10 mm in diameter, although a relationship between the cyst size and
      the onset of symptoms has been proved to be irrelevant in many cases. There is
      agreement that surgical intervention should be undertaken in patients presenting
      with hydrocephalus, progression of neurologic symptoms, or cyst enlargement.
      Tissue sample of the pineal lesion can be obtained by open surgery, stereotaxy
      and neuroendoscopy.

PMID- 20055264
TI  - Neuropathic pain.
AB  - Neuropathic pain refers to pain that originates from pathology of the nervous
      system. Common causes of neuropathic pain are diabetes mellitus, reactivation of
      herpes zoster, nerve compression or radiculopathy, alcohol, chemotherapy or abuse
      of some drugs, and trigeminal neuralgia. Specific symptoms of neuropathic pain
      are mechanical allodynia and cold hyperalgesia. Drugs to treat neuropathic pain
      can be divided into adjuvant analgesics (antidepressants and anticonvulsants),
      opioids and topical agents. The use of multiple drug therapies is common in
      practice. Despite considerable increase in the number of randomized placebo
      controlled trials in neuropathic pain in the last few years, the medical
      treatment of neuropathic pain is still far from being satisfactory, with less
      than half of patients achieving significant benefit with any pharmacological
      drug.

PMID- 20055265
TI  - The art: neuroscientific approach.
AB  - Scientists have for centuries tried to localize and define artistic talent.
      Modern diagnostic techniques that enable visualization and measurement of brain
      morphology and function are positron emission tomography (PET), magnetic
      resonance imaging (MRI), functional transcranial Doppler (fTCD) and some
      biochemical methods. In the majority of people, the left hemisphere is dominant,
      but the right hemisphere is considered to be creative, visual, imaginative and
      intuitive. Right hemisphere is associated with musical skills and good three
      dimensional orientation. It is also associated with good coordination and
      athletic skills. Creative people have less marked hemispheric dominance. Using
      the functional (fMRI) technique, the activation of visual cortex while watching
      different kinds of compositions was visible; the specific pattern of cortical
      activation was identified for looking at the landscapes, portraits, abstract
      compositions or different combination of colors. For music perception, the
      interplay of activity on both sides of the brain is necessary. In the right side,
      the centers for perceiving pitch, certain aspects of melody, harmony, timbre and
      rhythm are placed, and in the left side the processes of rapid changes in
      frequency and intensity, both in music and words are taking place. Adaptation of
      the brain, i.e. brain plasticity can arise upon listening or performing music. It
      is possible to use music, painting and dancing as an aid in the treatment of
      somatic, neurologic or psychiatric disorders.

PMID- 20055266
TI  - There is no healthy level of smoking.
AB  - Cigarette smoking is the leading preventable cause of death in the world.
      Nicotine is a highly addictive substance. Nicotine dependence is a major barrier
      to successful smoking cessation. Smoking is a risk factor for 30 diseases with a
      high rate of morbidity and mortality. There is no safe level of smoking. Help and
      support to smoking cessation should be an integral part of treatment,
      particularly for cardiovascular and cerebrovascular diseases. Prevention of
      smoking and effective treatment for nicotine dependence can significantly
      decrease the risk of vascular and malignant diseases.

PMID- 20055267
TI  - Parkinson's disease.
AB  - Parkinson's disease is one of the most common neurodegenerative diseases caused
      by degeneration of dopaminergic neurons in substantia nigra. The neuropathologic
      hallmark of Parkinson's disease is the presence of Lewy bodies composed mostly of
      alpha-synuclein and ubiquitin. It is believed that the occurrence of Parkinson's
      disease is due to a combination of genetic and environmental factors, but the
      exact mechanism of Parkinson's disease development is not fully elucidated. The
      most characteristic motor symptoms for Parkinson's disease include bradykinesia,
      rigidity, resting tremor and postural instability, while many patients also have
      non-motor signs and symptoms. The key therapeutic agent in the treatment of
      Parkinson's disease is L-dopa, and the others are dopaminergic agents, monoamine
      oxidase-B (MAO-B) inhibitors, catechol-O-methyltransferase (COMT) inhibitors,
      amantadine and anticholinergic agents.

PMID- 20055268
TI  - Possible causes of vitamin D deficiency (VDD) in Pakistani population residing in
      Pakistan.

PMID- 20055269
TI  - Elderly abuse: tip of the ice berg.

PMID- 20055270
TI  - Postmortem computed tomography for diagnosis of cause of death in male prisoners.
AB  - OBJECTIVE: To determine the utility of postmortem CT (PMCT) examination in
      establishing the cause of death among male prisoners dying in Karachi jails.
      METHODS: A descriptive study was carried out from February 2006 to September
      2007, CT Scan section, Civil Hospital Karachi and the Mortuary, Dow Medical
      College, Dow University of Health Sciences, Karachi. Adult male prisoners dying
      in the Karachi central prison and referred to the study setting for determining
      the cause of death for medico legal purpose were included. Female prisoners and
      those cases where the final report of cause of death was not available were
      excluded. CT scan of the vital body regions (head, neck, thorax, abdomen and
      pelvis) was carried out in all cases. The scan was read and reported by two
      radiologists. Anatomical dissection based autopsy was carried out by the forensic
      expert. Final report regarding the cause of death was issued by the forensic
      expert based on the combined findings, histopathology, toxicology results and
      circumstantial evidence. The CT scan and autopsy findings were compared and
      percentage agreement was determined using kappa statistics. RESULTS: There were
      14 cases in all with mean age of 41.2 +/- 17 years. The alleged mode of death was
      custodial torture in all cases. CT scan determined the cause of death to be
      natural cardio-respiratory failure in 10, strangulation in 01, pulmonary
      tuberculosis (TB) in 02 and trauma to spine in 01 case. The autopsy determined
      natural death in 11 and pulmonary TB in 02 and asphyxia in 01. The percentage
      agreement between CT and autopsy was 92% (k = 0.92) and between CT and finalized
      cause of death was 100% (k = 1.0). CONCLUSION: PMCT is as effective as dissection
      autopsy in identifying pulmonary infections and natural causes of death. It is
      more effective in identifying vertebral fractures which may exclude hanging and
      corroborate trauma to spine.

PMID- 20055271
TI  - Frequency, characteristics and risk factors of carotid artery stenosis in
      ischaemic stroke patients at Civil Hospital Karachi.
AB  - OBJECTIVE: To determine the frequency and characteristics of carotid artery
      stenosis in acute ischaemic stroke patients and to assess the significance of
      common risk factors for carotid stenosis in these patients. METHOD: One hundred
      consecutive patients admitted with acute ischaemic stroke were included in the
      study. The relevant history, physical examination and laboratory investigations
      were done as per the Performa. Doppler ultrasound was performed during the
      hospitalization to find out carotid artery stenosis. Statistics analysis was done
      with SPSS v 14. RESULTS: Out of one hundred (100) patients, sixty one (61%) were
      males and thirty nine (39%) were females. Thirty nine patients (39%) were found
      to have carotid artery stenosis, all of them on the ipsilateral side
      corresponding to the ischaemic lesion. Eleven (11) of these patients had stenosis
      on the contra lateral side as well. The presence of stenosis was significantly
      correlated with older age and the presence of multiple risk factors. Majority
      (52%) of the lesions were severe to critical as determined by Doppler peak
      systolic velocity. Fifty nine (59%) were non calcified. CONCLUSION: Carotid
      artery stenosis is strongly associated with ischaemic stroke. Doppler studies are
      recommended for the high risk patients for the primary as well as secondary
      prevention of ischaemic stroke.

PMID- 20055272
TI  - Variables predictive of outcome in patients with acute hypercapneic respiratory
      failure treated with noninvasive ventilation.
AB  - OBJECTIVE: To assess results with NIV in acute hypercapneic respiratory failure
      and to identify outcome predictors. METHODS: This was a retrospective
      observational study on consecutive patients presenting with acute type II
      respiratory failure and meeting criteria for NIV use over a 5 year period.
      Patients presenting with haemodynamic instability, inability to protect their
      airway, malignant arrhythmias and recent oesophageal surgery were excluded.
      Univariate and Multivariate regression analysis was used to determine the impact
      on survival. A p value of < 0.05 was considered statistically significant.
      Software used was SPSS 14. RESULTS: Total numbers of patients included were 119;
      52.9% were males. Mean age was 63.4 +/- 11.9 years. Overall Survival to discharge
      rate was 76.5%, intubation rate was 12.6% and mean length of stay was 11.4 +/-
      10.9 days. Statistically significant improvements were observed in the pH and
      PaCO2 at 24 hours and 48 hours compared to baseline (7.28 v/s 7.37, p < 0.001;
      74.2 v/s 65, p < 0.001). On multivariate regression analysis, sepsis at admission
      predicted mortality (adjusted Odds ratio 26.4; 95% CI 2.3, 304, p < 0.009). A
      serum HCO3 > 35 Meq/L (adjusted Odds ratio 0.9; 95% CI 0.83, 0.98, p < 0.015)
      identified those less at risk for intubation. CONCLUSION: NIV was found to be
      both safe and effective in the management of acute hypercapneic respiratory
      failure. Sepsis and serum HCO3 at admission identified patients having poor
      outcomes.

PMID- 20055273
TI  - Frequency of hypothyroidism in patients of beta-thalassaemia.
AB  - OBJECTIVE: To determine the frequency of hypothyroidism in patients suffering
      from homozygous beta-thalassaemia. METHODS: This descriptive study included 70
      diagnosed thalassaemia major patients aged 5-14 years. Demographic data as well
      as history of blood transfusion and chelation therapy was collected. Random blood
      samples were drawn and thyroid profile (serum thyroxine [T4], triiodothyronine
      [T3] and thyroid stimulating hormone concentrations [TSH]) was done by enzyme
      linked immunosorbent assay (ELISA). Primary hypothyroidism was defined by a TSH
      level > 4 microIU/ml. Results were analysed by descriptive statistical methods.
      RESULTS: Primary hypothyroidism was seen in 18 (25.7%) patients. Of these, 17 had
      normal T4 levels with elevated TSH levels consistent with a diagnosis of
      compensated primary hypothyroidism whereas only one patient showed a decreased T4
      level with elevated TSH (uncompensated primary hypothyroidism). Mean age of
      hypothyroid patients was 9.2 +/- 2.6 years. Frequency of hypothyroidism was
      associated with increased serum ferritin levels. CONCLUSION: Primary
      hypothyroidism occurs in a significant proportion of thalassaemia major patients
      in the absence of obvious clinical signs of hypothyroidism. Regular follow-up for
      early detection and timely treatment of such complications could improve the
      quality of life of these patients.

PMID- 20055274
TI  - Maternal mortality in rural community: a challenge for achieving millennium
      development goal.
AB  - OBJECTIVES: To asses the Maternal Mortality Ratio and the causes of maternal
      death over a period of three years in one of the rural district of Sindh
      Province, Pakistan. METHODS: A retrospective analysis of maternal mortality was
      carried out for a period of 3 years from 2006 to2008 by reviewing the maternal
      mortality record and statistics of National Programme for Family Planning and
      Primary Health Care of District Matiary, Sindh Province Pakistan. The information
      regarding demographic, reproductive parameters and verbal autopsy questions was
      collected and analyzed by SPSS V 16. RESULTS: The cumulative MMR was 297/100,000
      live births. The direct causes accounted for 58 (80.5%) deaths. The high ratio of
      maternal mortality was found in women of age 29-39 years and in Para > 4. Thirty
      five (48.6%) maternal deaths occurred at tertiary care hospitals, while 20
      (27.8%) and 16 (22.2%) took place at home and on the way to hospital
      respectively. CONCLUSION: Maternal Mortality in rural areas of Sindh Province
      Pakistan is still a challenge for the achievement of the Millennium development
      Goal (MDG).

PMID- 20055275
TI  - Changing trends of infective endocarditis.
AB  - OBJECTIVE: To determine the frequency of culture positive and culture negative
      endocarditis and type of organisms causing bacterial endocarditis in patients
      admitted at National Institute of Cardiovascular Diseases (NICVD), Karachi.
      METHODS: This was a cross sectional, descriptive study conducted from 29th March
      2006 to 13th October 2006 at National Institute of Cardiovascular Diseases,
      Karachi. All patients having clinical suspicion of infective endocarditis were
      admitted and worked up. Seventy five patients having definite infective
      endocarditis as per Duke Criteria were included. RESULTS: There were 55 (70%)
      males and 20 (30%) females. Mean age of the patients was 23 +/- 8.9 years. Ninety
      percent of the patients were below 40 years of age. Six patients had prosthetic
      valve and six were intravenous drug abusers. The commonest signs and symptoms
      observed were fever, shortness of breath, weight loss, murmur, pallor and
      splenomegaly. Mitral valve was affected in majority of patients. Blood cultures
      were positive in 40 (53.3%) cases while 35 (46.7%) cases were culture negative.
      Nine (22.5%) patients out of 40 culture positive cases and 29 (82.8%) patients
      out of 35 culture negative cases were using antibiotics before admission. All six
      intravenous drug abusers showed culture positive endocarditis. Among culture
      positive cases, staphylococcus group was found in 21 (52.5%) cases while
      streptococcus group in 11 (27.5%) cases. Coagulase negative staphylococci were
      found to be the most common organism, that is 14/40 (35%) patients. CONCLUSION:
      Changes in spectrum of organisms causing bacterial endocarditis reported by
      western researchers do exist in our community. To know the reason behind these
      changing trends needs further advanced studies and evaluation.

PMID- 20055276
TI  - Retrospective study of 213 cases of female urogenital fistulae at the Department
      of Urology & Transplantation Civil Hospital Quetta, Pakistan.
AB  - OBJECTIVES: To review our experience in causes, diagnosis and basic principles of
      surgical treatment of urogenital fistulae. METHODS: A retrospective study of 213
      patients with different types of urogenital fistulae were reviewed between
      October 1995 to October 2008. They were analyzed with regard to age, parity,
      causal factor, mode of treatment and outcome. Patients were also evaluated at two
      or three weeks initially, three monthly and later depending upon symptoms.
      RESULTS: We reviewed our series of female urogenital fistulae treated over a 13
      years period. Out of these 213 cases, 133 (62.44%) were Vesico vaginal fistulae,
      54 (25.35%) Urethro vaginal fistulae and 26 (12.2%) were Uretero vaginal.
      Majority of the patients were young in child bearing age between 16 and 30 years
      of age, although age range was wide i.e., 11 to 50 years. The most common cause
      of urogenital fistulae were Obstetrical trauma due to obstructed labour in 50
      (37.59%) and Gynaecological (hysterectomy 25 (18.79%) and caesarian section in 9
      (6.77%). Patients of Uretero vaginal fistulae were mainly due to unrecognized
      ureteral injuries during Gynaecological procedures (hysterectomy in 17 cases and
      caesarian section in 5 cases). For repair of vesico vaginal fistulae,
      Transvaginal route for repair was used in 53 (39.84%) patients, while Trans
      abdominal route for repair was used in 70 (52.63%) patients. There were 16
      (12.03%) failures in Vesico vaginal fistulae with a success rate of 88%. Mean
      Hospital stay was 15 +/- 3.5 days (range 4-30 days) and a mean follow-up of 8 +/-
      3.2 months (range 4 months to 2 years). CONCLUSIONS: In this series, most of the
      female urogenital fistulae were vesico-vaginal with majority of the women being
      in the child bearing age. The most common cause was obstetrical trauma.

PMID- 20055277
TI  - Integration of informal medical practitioners in DOTS implementation to improve
      case detection rate.
AB  - OBJECTIVE: To integrate informal registered medical practitioners (IRMP) in
      Directly Observed Therapy Short Course (DOTS) implementation to improve case
      detection rate. METHODS: This interventional study was conducted in the
      settlement area of Malir district whereas New Karachi was taken as control,
      between February to November 2005. All registered healthcare providers within 5
      kilometer around Tuberculosis (TB) DOTS center Malir were included. New sputum
      positive and sputum direct smear negative cases of pulmonary Tuberculosis above
      15 years residing in the catchments area were included as target population.
      Informal registered medical practitioners were trained for the referral of
      suspected cases to the TB DOTs center where three sputum samples were taken, and
      X-ray chest was done to confirm if sputum direct smear (D/S) was negative.
      Demographic data regarding age, gender, address, case number, onset of symptoms,
      treatment given, response, compliance to treatment was all collected. RESULTS:
      Out of 64 health care providers there were a drop out of 6 leaving 58 informal
      registered medical practitioners (36 homeopathic/22 Hakims) who referred 54
      cases, of these 16 cases were actual suspects. Two out of these 16 (12.5%) were
      Tuberculosis positive. One was Sputum D/S positive and the other sputum direct
      smear negative with X-ray chest positive. Comparison of data (Malir and New
      Karachi diagnostic center) showed that by incorporating homeopathic and Hakims an
      increase in the proportion of case identification (0.477) was significantly
      higher in Malir (intervention area) vs New Karachi (non-intervention area)
      (0.316). CONCLUSION: Integration of informal registered medical practitioners was
      found to be effective in DOTS implementation hence they can be incorporated in
      other national programmes to improve public health.

PMID- 20055278
TI  - Frequency and pattern of gonorrhoea at Liaquat University Hospital, Hyderabad (a
      hospital based descriptive study).
AB  - OBJECTIVE: To determine the frequency and pattern of gonorrhoea at Liaquat
      University Hospital, Hyderabad. METHODS: This descriptive study of eight months
      was conducted at Liaquat University Hospital Hyderabad, Sindh, Pakistan from
      December 2007 to May 2008. All patients who were above 14 years of age and came
      with history of discharge from penis or vagina were evaluated and enrolled in the
      study. After recording demographic data these were screened for gonococcal
      infection by Gram's staining method. The frequency was determined by identifying
      the positive gonococcal infected patients while pattern was observed according to
      the presentation of patients. The data was analyzed by SPSS version 10.00.
      RESULT: One hundred and eighteen patients, 92 (78%) male and 26 (22%) females
      were identified to have infection out of 266 patients with mean age 27.4 +/- 7.77
      years. Majority of the patients 92 (78%), presented in the department of
      dermatology. In the study group, 77 (65%) were unmarried and 41 (35%) were
      married, 71 (60%) belonged to Hyderabad and 47 (40%) came from periphery of Sindh
      province of Pakistan. Other features and presentation identified in such patients
      were painful micturition 98 (83%), burning micturition 94 (80%), frequent
      micturition 108 (92%), genital itching 85% (72%), intermenstrual bleeding 09
      (8%), painful sexual intercourse 87 (74%) and skin lesions 24 (20%). All patients
      were treated by syndromic management. CONCLUSION: A relatively high prevalence of
      gonorrhoea (46% patients) was detected in the patients seen in Liaquat University
      Hospital.

PMID- 20055279
TI  - Prevalence and risk factors for stunting among children under 5 years: a
      community based study from Jhangara town, Dadu Sindh.
AB  - OBJECTIVE: To assess the prevalence and the associated risk factors for stunting
      in Jhangara Town, Dadu Sindh. METHODS: A cross-sectional survey was conducted in
      Jhangara Town, located in district Dadu, rural Sindh. A total of 800 children
      less than 5 years of age were enrolled. A questionnaire was used to elicit
      required information and anthropometric measurements were made. RESULTS: The
      overall prevalence for stunting was 61% in the study population, which was higher
      than the prevalence reported by Pakistan Demographic Health Survey (PDHS)
      1990/91. In multivariate analysis various risk factors for stunting were
      ethnicity (OR = 2.1, 95% CI 1.27- 3.57) and birth interval < two years (OR = 1.5,
      95% CI 1.09 - 1.99). CONCLUSION: A large number of children below 5 years of age
      were stunted. Ethnicity and birth interval less than 2 years were the important
      risk factors.

PMID- 20055280
TI  - Factors influencing morbidity and mortality in elderly population undergoing
      inguinal hernia surgery.
AB  - OBJECTIVE: To study various factors influencing outcome of open hernia repair in
      elderly population. METHODS: This is a retrospective descriptive study from
      January 2004 to December 2008 including all patients (n = 212) of 60 years and
      above operated for inguinal hernias either electively or in emergency during this
      period. One of the co-authors was assigned the duty to collect the record files
      of all patients over 60 years age operated for inguinal hernia in the department
      of surgery LUMHS as well as in private hospitals in Hyderabad. The records of all
      patients were reviewed and data retrieved on a proforma mentioning variables to
      investigate the common co-morbidities and their influence on the overall results
      of surgical intervention in geriatric patients. SPSS version 12 was used for
      statistical analysis of the data. RESULTS: The mean age of the patients in this
      series was 69.82 +/- 7.8 years of whom 208 (98%) were males and 4 (2%) females.
      In 190 (89.61%) patients the hernias were unilateral while 12 (5.7%) cases had
      bilateral inguinal hernias and 10 (4.7%) patients presented with recurrent
      hernias. In 159 (75%) patients the hernia was simple while 53 (25%) patients
      presented with one or the other complication such as obstruction or
      strangulation. Elective surgery was performed in 161 (75.9%) patients while 51
      (24.1%) patients were operated in emergency. Co-morbidities were present in 79
      (37.26%) patients. Out of the total study population, 7 (3.30%) patients died of
      which 6 were operated in emergency and had co-morbidities. All of them had
      gangrene of bowel for which resection and anastomosis was done. One patient died
      of acute MI on 5th post-operative day. CONCLUSION: Emergency hernia surgery
      carries a high mortality in elderly patients. Co-existing medical problems make
      surgery still challenging in the geriatric population. An early elective hernia
      repair is highly recommended.

PMID- 20055281
TI  - Evaluation of Iranian microbiology laboratories for identification of etiologic
      agents of bacterial meningitidis. Survey results of an external quality
      assessment scheme (EQAS) programme.
AB  - OBJECTIVE: To determine the ability of Iranian microbiology laboratories for
      identification and susceptibility testing of Streptococcus pneumoniae and
      Haemophilus influenzae as causative agents of bacterial meningitides. METHODS:
      Two strains of bacteria including Haemophilus influenzae and Streptococcus
      pneumoniae as a common causative agents of meningitides were chosen and coded as
      strain number 1 and number 2. The strains were distributed among 679 microbiology
      laboratories. All laboratories were requested for identification of each unknown
      microorganism and susceptibility testing of S. pneumoniae against five commonly
      used antibiotics. RESULTS: Of 679 microbiology laboratories 310 (46%)
      laboratories participated in the survey and among these, 258 laboratories
      completely identified S. pneumoniae. About 85% laboratories produced correct
      susceptibility testing against oxacillin, erythromycin, tetracycline, and
      vancomycin. Of 310 received responses only 50 laboratories identified H.
      influenza correctly. The majority of the laboratories did not have the capacity
      to identification H. influenza. CONCLUSION: Microbiology laboratories in our
      country are qualified for identification and susceptibility testing of S.
      pneumoniae. However, majority of laboratories are not qualified for
      identification of H. influenzae.

PMID- 20055283
TI  - Recurrent urinary tract infections in females.
AB  - Uncomplicated Urinary tract infections are common in adult women across the
      entire age spectrum, with mean annual incidence of 15% and 10% in those aged 15
      39 and 40-79 years, respectively. Urinary tract infection (UTI), with its diverse
      clinical syndromes and affected host groups, remains one of the most common but
      widejly misunderstood and challenging infectious diseases encountered in clinical
      practice. Recurrent urinary tract infections (UTIs) present a significant problem
      for women and a challenge for the doctors who care for them. The diagnosis of
      uncomplicated UTI can be achieved best by a thorough assessment of patient
      symptoms with or without the addition of a urine dipstick test. Treatment should
      be based on the most recent guidelines, taking into account resistance patterns
      in the local community. The patient who suffers from recurrent UTIs can be
      treated safely and effectively with continuous antibiotic prophylaxis, post
      coital therapy, or self-initiated treatment. This review article covers the
      latest trends in the management of recurrent UTI among women. Further research is
      needed regarding rapid diagnosis of UTI, accurate presumptive identification of
      patients with resistant pathogens, and development of new antimicrobials for drug
      resistant UTI.

PMID- 20055282
TI  - Beliefs and perceptions of acne among a sample of students from Sindh Medical
      College, Karachi.
AB  - OBJECTIVE: To determine the beliefs of undergraduate medical students regarding
      acne. METHOD: A cross-sectional study in 630 medical students (aged 16-29 years)
      was conducted. A voluntary self administered questionnaire was used to collect
      data regarding their beliefs and perceptions about acne. Both acne and non-acne
      sufferers were included in the study. RESULT: Of the 630 respondents, 55.9% were
      sufferers while 44.1% were non-sufferers. Of all, 67.0% of the affected believed
      it to be relieved by frequent face washing and that they should seek treatment,
      whereas 79.84% students believed in seeking dermatologist's advice regarding
      treatment. Mass media was the most common source of information. As to the cause,
      21.7% students believed that hereditary factors and 20.1% thought environmental
      factors are the major cause of acne. In diet, soft drinks (29.2%) were considered
      the major exacerbating factor. The most significant emotional impact of acne on
      medical students was embarrassment (26.2%). CONCLUSION: The results of this study
      pointed out that misconceptions and false beliefs on acne are widespread and
      enduring among Medical students' too. Health education programme on acne is
      needed to improve their understanding of the condition.

PMID- 20055284
TI  - Pneumoperitoneum, pneumoretroperitoneum and bilateral pneumothorax caused by
      ERCP.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the mainstay
      procedure treatment of hepatobiliary and pancreatic diseases. Life-threatening
      complications such as pneumoperitoneum, pneumoretroperitoneum, pneumomediastinum,
      subcutaneous emphysema and pneumothorax related to this procedure rarely occur
      and only a few cases are reported in English literature. Herein, we report a
      patient who developed acute abdominal symptoms with subcutaneous emphysema and
      bilateral pneumothorax due to duodenal perforation, accompaniment of ERCP that
      was successfuly treated.

PMID- 20055285
TI  - Partial ureterectomy for a huge primary leiomyoma of the ureter.
AB  - A case of a huge primary leiomyoma of the ureter in which only partial
      ureterectomy was performed is presented. The benign nature of the mass was
      primarily confirmed with frozen section at the time of surgery and then with
      immunohistochemistry (IHC). To the best of our knowledge, this case is a unique
      form of leiomyoma of the ureter due to its large size. There have been only ten
      cases of primary leiomyoma of the ureter reported since 1955 and all of them were
      very small in size. Our case is considered to be the eleventh.

PMID- 20055286
TI  - Successful use of rituximab in Evans syndrome and refractory immune
      thrombocytopenic purpura.
AB  - Immune cytopenias are mediated by auto-antibodies produced by B-lymphocytes.
      Conventional treatment of immune-mediated haematological disorders includes
      immunosuppression with steroids and other immune modulating therapies and in some
      refractory cases, splenectomy. Response rates to conventional and second-line
      agents are variable and a proportion of patients require lifelong
      immunosuppression to maintain the disease in remission. Rituximab, an anti- CD 20
      monoclonal antibody has gained widespread acceptance in the management of B-cell
      malignancies. Additionally, it has been used to treat the disorders associated
      with autoantibody production. We report herein the successful use of Rituximab in
      the treatment of two patients with autoimmune cytopenias one had Evan's syndrome
      and other had refractory immune thrombocytopenic purpura. Both of these patients
      are still in remission at 16 and 25 months following treatment.

PMID- 20055287
TI  - Mental capacity: is it important in our daily practice?

PMID- 20055288
TI  - Knowledge attitude and practices of undergraduate students regarding first aid
      measures.
AB  - OBJECTIVES: To assess knowledge, attitude and practices of first aid measures in
      undergraduate students of Karachi. METHODS: A cross-sectional study was carried
      out at six colleges of Karachi, three of which were medical colleges and three
      non-medical colleges. Knowledge was assessed regarding various emergency
      situations with the help of a questionnaire. The target population size was 460,
      based on 50% prevalence and 95% confidence interval. The eventual sample size
      achieved was 446. RESULTS: A total of 446 students were interviewed. Seventy
      eight students (17.5%) had formal First Aid (FA) training. The mean number of
      correct answers of students with FA training was 10.3 (+/- 3.5) as opposed to
      8.58 (+/- 4.0) in those without FA training (p < 0.001, 95% CI) with a mean
      difference of 7.84%. The mean number of correct answers by medical students with
      FA training was 11.2 (+/- 2.9) as opposed to 7.2 (+/- 3.43) by non-medical
      students (p < 0.001, 95% CI) with a mean difference of 18.14%. Students having
      received formal first aid training scored better than those who had not (p <
      0.001). CONCLUSION: First aid training programmes should be introduced at school
      and college level in developing countries to decrease the early mortality and
      morbidity of accidents and emergencies.

PMID- 20055290
TI  - Balancing the equation: medical students and health research.

PMID- 20055289
TI  - Depression during pregnancy: causes, risk factors and treatment.

PMID- 20055291
TI  - Obstructive sleep apnoea: awareness regarding risk factors.

PMID- 20055292
TI  - [On surgery experts].

PMID- 20055293
TI  - [One-year survival outcomes in patients with pancreatic head and portomesenteric
      veins resection].
AB  - INTRODUCTION: Hemipancreatoduodenectomy is a standard technique for surgical
      management of pancreatic head carcinomas. However, so far, mesenteric and/or
      portal vein resections have not been commonly indicated. This original report
      presents one-year survival outcomes in a group of operated subjects. METHODOLOGY:
      From 7/2005 to 7/2008, 13 pancreatic resections with concomitant resection of the
      mesenteric or portal vein were performed in the IKEM Transplant Surgery Clinic.
      The study objective was to assess the perioperative complications and 30-day
      mortality rates, and the overall survival period. RESULTS: The study group
      included 13 patients, 8 males and 5 females, the mean age was 66 (48 to 85)
      years. Concomitantly, resection of the portal vein (6x) or the superior
      mesenteric vein (3x), or of the both veins (4x) was performed. In 11 subjects of
      this patient group, the time period between the surgical procedure and the
      assessment was over a year. During the portomesenteric reconstruction phase, end
      to-end anastomoses were performed in eight subjects, and the resected vein was
      replaced with the internal jugular vein in two subjects. In three subjects, the
      venous wall excision site was closed using a simple defect suture. Out of the
      study group, 5 subjects were surviving at 12 months. Three patients exited due to
      their primary diagnosis and the fourth one for internal complications two months
      after the procedure. CONCLUSION: The authors belive that
      hemipancreatoduodenectomy with concomitant resection of portomesenteric veins
      should become a standard treatment method in indicated patients, performed in
      specialized centres.

PMID- 20055294
TI  - [An optimum miniinvasive approach in esophageal replacement with stomach].
AB  - Esophagectomy was performed by transhiatal approach from laparotomy or laparotomy
      combinated with thoracotomy till the beginning of 90th of 20th century. These
      procedures are associated with high morbidity (40-80%) and mortality (5-15%)
      rate. There is a tendency of using minimally invasive approach in esophageal
      surgery with preserving oncological radicality. Based on our experiences with
      minimally invasive esophagectomy and gastric replacement we would like to
      introduce a technique which is considered optimal in our department.

PMID- 20055295
TI  - [GIST as a cause of the small intestine invagination].
AB  - A case report describing intusussception on small bowell as a one of the less
      frequent causes of ileus in adults. A gastointestinal stromal tumor ( GIST) was
      found as a lead point of the intusussception on the basis of abdominal CT.
      Patient underwent resection of small bowel with tumor. Basic knowledge of GISTs
      is discussed.

PMID- 20055296
TI  - [Significance of the TPS cytokeratin marker in the postoperative follow up of
      colorectal carcinoma patients].
AB  - AIM: Examination of tumour markers conducive to follow up of the patients with
      colorectal carcinoma. MATERIAL AND METHODS: The tumour markers were examined in
      the population of patients with primarily established and histologically verified
      colorectal adenocarcinoma. RESULTS: The resection therapy resulted in the
      decrease in post-operative CEA levels. There were no changes in pre- and post
      operative CA 19-9 levels; unlike with post-operative TPS levels having been
      significantly increased, probably due to reparation processes resulting from the
      surgery. It can be concluded that pre- and post-operative CEA levels are the most
      suitable markers to check the effect of surgery. With a 95%-specificity for the
      establishment of recidives, the highest sensitivity was reached with TPS (83%);
      the sensitivities of the classical tumour markers CEA and CA 19-9 were
      significantly lower (41% and 25%, respectively). The results should be
      interpreted with caution due to a small number of relapses regarding a short
      follow up and rather local-regional character of the recidives. CONCLUSION:
      However, TPS seems to be a promising marker for the follow up of the patients
      with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and
      TPS.

PMID- 20055297
TI  - [Transarterial chemoembolization in hepatocellular carcinoma].
AB  - INTRODUCTION: Hepatocelullar carcinoma (HCC) is the fifth most common cancer in
      the world. It mostly occurs in patients with cirrhosis. In the Czech Republic,
      about 250 new cases are reported per year. Surgery, i.e. liver resection or
      transplantation, as the only potentially curable method is possible in 15-20% of
      them. For the rest, palliative treatment is indicated. This includes ablative
      methods (radiofrequency ablation, alcoholization), transarterial
      chemoembolization (TACE), systemic chemotherapy or biological treatment by
      sorafenib. TACE is method of choice in patients unsuitable for surgery and
      ablative treatment. Another indication is embolization of HCC before liver
      transplantation to prevent tumour progression. In combination with other methods,
      down staging of the tumour and curable treatment afterward is possible. AIMS: To
      assess the outcome of transarterial chemoembolisation in patients with
      hepatocellular carcinoma. METHODS: Between 2004-2008 we performed 30 TACE. Of
      that number, 28 TACE were performed in 20 patients with HCC. We super selectively
      catheterized the tumour via arteria femoralis and used Doxorubicin with Lipiodol
      as embolic material. In follow up, we carried out laboratory studies and CT.
      RESULTS: We have not noticed any major complications. Post-embolization syndrome
      with fever, nausea and right upper quadrant pain occurred after 10 TACE (33%).
      One-, two- and three years survival of the patients was 53%, 40% a 20%.
      CONCLUSION: TACE is safe method prolonging patients' survival with unresectable
      HCC. For the correct treatment of HCC, its concentration to cancer centres and
      the cooperation between multiple specialists is necessary.

PMID- 20055298
TI  - [120 laparoscopic adrenalectomies with a harmonic scalpel].
AB  - BACKGROUND: Presently the laparoscopic adrenalectomy (LA) becomes most popular
      since 1992 when it was performed for the first time by laparoscopic method by
      Gagner. Typical indication for LA is the aldosteron-secreting adenoma, Cushing's
      syndrome, feochromocytoma or scarcity tumors such as adrenal cyst or
      myelolipomas. AIM: The evaluation of the laparoscopic adrenalectomy as safe
      method for adrenals tumout's extirpation to the sizes 10 cm. METHODS: LA is
      provided with transperitoneal lateral approach most frequently then in back side
      position. Retroperitoneal approach is used less commonly. RESULTS: Since 2006,
      firstly at the 1st Surgical department of 1st Medical School of Charles
      University and General Faculty Hospital and lastly at the Surgical department 2nd
      Medical School of Charles University and Central Military Hospital, has been
      performed on the whole 120 LA in 114 patients. The bilateral LA was performed in
      6 patients. The conversion from the laparoscopic to open adrenalectomy was
      necessary by reason of the king size of the tumor (13/14 cm) in two cases. The
      lateral position and transperitoneal approach was used in all cases. The harmonie
      scalpel was used with advantage. Average length of the operation was 82 minutes
      (40-154 min), respective 180 minutes (130-270 min) in the case of the bilateral
      LA. The median size of the adrenal tumor was 4.9 cm (1.5-12.5 cm) with average
      weight 44 g (18-421 g). All of the patients after LA were monitored for 24 hours
      in the Intensive care units. The average time of the hospitalization was 3.7 days
      (2-6 days). CONCLUSION: Laparoscopic adrenalectomy presently becomes as the "gold
      standard" for the treatment of adrenal tumors to the size 10 cm namely and in the
      event of malignancy. The harmonie scalpel is useful and sparing advice for the
      LA.

PMID- 20055299
TI  - [Crural arteries PTA in patients with diabetes].
AB  - AIM: The authors analyse the patients hospitalized with a neuroischemic diabetic
      foot. They evaluate experiences and results of the crural arteries percutaneous
      transluminal angioplasty (PTA) in the diabetic patients. METHOD: It is a
      retrospective analysis of the patients hospitalized during years 2005-2008 at the
      Department of Vascular Surgery of the Teaching Hospital J. A. Reiman Presov with
      the diabetic foot. During the study period 265 hospitalization in 205 patients
      were registered for complications of the diabetic foot. PTA of the crural
      arteries was performed on 74 lower extremities in 68 patients. 133 crural
      arteries were revascularized in this group of the patients. Indication for
      execution of the crural arteries PTA in the diabetic patients was critical limb
      ischemia on 68 revascularized lower extremities (91.9%). RESULTS: Technical
      success (residual stenosis no more than 30%, unobstructed revascularized crural
      artery to periphery) was achieved on 93 revascularized crural arteries (69.92%).
      They have control examination minimally 12 months after PTA in 54 revascularized
      lower extremities of the 68 patients with the neuroischemic diabetic foot. From
      this subset of the patients 28 lower extremities (51.85%) are healed according to
      clinical examination, on 7 lower extremities (12.96%) clinical signs of critical
      limb ischemia remain, 10 times (18.52%) low amputation was performed and 9 times
      (16.67%) high amputation was executed. CONCLUSION: The authors believe that PTA
      of the crural arteries is safe and effective method of critically ischemic
      diabetic foot revascularization. If revascularization is successful, it can
      effectively contributes to the lower extremity salvage of the patient with
      neuroischemic diabetic foot.

PMID- 20055300
TI  - [Posttraumatic muscular forearm hernia].
AB  - Symptomatic posttraumatic muscular herniation is a very rare complication of
      forearm fracture. We report a case of symptomatic musular herniation tretaed with
      an autologous fascia lata onlay graf.

PMID- 20055301
TI  - [Lesions in the popliteal fossa with neurologic symptomatology--case reports,
      diagnostics and treatment].
AB  - The lesions arising in the popliteal fossa are varied. We report two different
      lesions related to the peroneal nerve that presented with neurologic symptoms.
      Both were initially treated at surgical department with insufficient diagnostics
      and finally required a neurosurgical operation. We emphasize performing complete
      diagnostics that may avoid unnecessary burden for the patient and healthcare
      personnel. Patients with proven intimate relation of the lesion to nerve
      structures in the popliteal fossa should be referred to neurosurgical department.

PMID- 20055302
TI  - [Treatment of the elderly in the regional surgical department].
AB  - A retrospective study of health problems among patients aged 80 and over was
      performed in the in-patient Department of Surgery, Karvina Hospital, since 2005
      to 2007. A total of 624 patients were hospitalized during the period under study,
      174 males and 450 females, the M:F ratio being 1 to 2.6. Most hospital stays were
      categorized as acute--583 (i.e., 80.3%). A total of 295 operations (i.e.,40.6%)
      have been performed. The two major reasons for hospitalization were: 1) The most
      frequent reasons for hospital admissions and treatment were as follows:
      unexplained abdominal pain--60 cases, cholecystopathy--48 cases, hematemesis or
      melena--43 cases, abdominal hernias--29 cases, vomiting--26 cases, intestinal
      passage impairments--24 cases, diarrhoea--17 cases. 2). Injuries--274 cases
      (i.e., 37.7%), of which 121 cases presented with the primarily treated diagnosis
      of proximal femoral neck fracture (44.2% of all injuries). There were 35 cases
      (i.e., 4.8%) presenting with impairments of lower extremity arterial blood
      supply. Interestingly, the proportion of 'surgical' malignant tumours in this age
      group has been found relatively low: only 61 cases in the span of 3 years, 27 of
      the cases being colorectal carcinomas. Other reasons for hospital treatment were
      less common. There were only 34 social hospitalizations (4.7%). 295 patients have
      undergone operations (40.6%). 53 patients died, mostly as a result of circulatory
      failure. Of those 53, 16 patients had undergone surgical procedures (9 abdominal
      surgeries and 5 above-knee amputations). The present article discusses, among
      other issues, the nursing problems of caring for aged persons when there is a
      large amount of behavioural disorders due to advanced vascular dementia.

PMID- 20055303
TI  - [Contribution of MRI to the thoracolumbar spine injuries diagnostics and
      therapy].
AB  - AIM: The aim of this study was to assess correlation between the degree of
      severity of the intervertebral disc injury and the vertebral enoplate injury,
      evaluated based on MRI, and the resulting final clinical condition and
      radiological findings. MATERIAL AND METHODOLOGY: The authors performed a
      prospective analysis of patients with thoracolumbar fractures type A1 or A3,
      without injuries to the nervous system. The study group included 73 subjects (the
      mean age was 45.52 years), 44 males and 29 females. The type A1 fracture group
      including 31 patients received conservative treatment and the type A3 fracture
      group including 42 subjects underwent surgery with posterior transpedicular (TP)
      fixation. After their injury, the patients were examined using plain x-rays, CT
      and MRI. At month 18 of their follow up, a control MRI examination was performed
      to assess spinal kyphotization, the spinal body height decrease and the clinical
      outcomes. RESULTS: The data underwent statistical evaluation. The conservative
      treatment group showed no statistically significant correlation between the
      severity of the intervertebral disc and vertebral enoplate trauma and the
      resulting final clinical outcome or radiological findings, however, the
      conservative treatment of the type A1 fractures failed in 9.3% of the subjects.
      This was due to the disc trauma and its consecutive replacement resulted in
      improvement of the clinical condition. Posterior TP fixation in the type A3
      fractures did not prevent statistically significant higher rates of kyphotization
      and reduced weight- bearing tolerance in patients with more severe disc and
      vertebral enoplate traumas (grade 3 or 4), compared to patients with less severe
      traumas (grade 2). CONCLUSION: Posttraumatic assessment of the disc and vertebral
      enoplate trauma severity using MRI is of significance for predicting the fracture
      healing prognosis, as well as the final clinical outcome of the procedure.

PMID- 20055304
TI  - [Contribution of abdominal sonography in acute appendicitis diagnostics--our
      experience].
AB  - Acute apendicitis is the most frequent case of acute abdomen. During a two year
      period (2006-2007) it was performed in Department of Surgery of Faculty Hospital
      in Pilsen 678 appendectomies, 30 days post-operative mortality rate was 0%.
      Abdomen ultrasonography like helping method to clinic examination was performed
      in 313 patients, suspect of acute appendicitis was in 191 patients (61%), in
      remaining patients was normal ultrasound picture.

PMID- 20055305
TI  - [PCCP versus standard proximal femoral nail in the treatment of pertrochanteric
      femoral fractures].
AB  - The aim of our study was to compare two groups of patients with pertrochanteric
      femoral fracture types 31 A1 A2 A3 according to the AO who were treated with two
      different types of implants. The first group of 54 consecutive patients with
      above mentioned types of femoral fractures were treated using Proximal
      reconstruction nail manufacturer Beznoska comp., which is a standard implant we
      have been using for two years. The second group of 33 patients were treated with
      a new implant PCCP (Percutaneous Compression Plate) manufacturer Orthofix. We
      evaluated the time of operation, total blood loss (hgb, htc, number of blood
      transfusions), peri- and postoperative complications and subjective feeling of
      pain using the VAS (Visual Analogous Scale). The patients were at the time of
      procedure and after one year follow-up. The operation time of the standard and
      new techniques were comparable. The miniinvasive technique of PCCP was
      accompanied with significantly lower blood loss and significantly lower intensity
      of pain after the procedure. There was no difference in number of complications.
      One-year follow-up assessment showed greater mortality in the patients treated by
      the standard Proximal reconstruction nail (Beznoska CR).

PMID- 20055307
TI  - [Delusions of beauty and professionalism].

PMID- 20055306
TI  - [The operation risks and the force of preoperative management].
AB  - The aim of this article is to summarize the current actual knowledge in
      possibilities of examination of patients' condition before surgery with respect
      to development of present operation risks and of a recovery phase in increased
      patients' co-morbidity and age. Not only a profile of our patients has changed
      partially as was mentioned above, but also the new diagnostics methods, non
      invasive and miniinvasive techniques have appeared, too. Also the new methods of
      preparation of surgical patients for surgery are arising during the last few
      years. They answer the previously presented points witch are established on an
      increased interest in the patients during the perioperative time period (ERAS
      enhanced recovery after surgery/fast track). New methods appreciated an operation
      trauma, which has a substantial influence on the result of an operation. The most
      frequent risks of an operation must be presented: anaesthetic, respiratory,
      cardial, nutritive, thromboembolic, and other specific risks subjecting to an
      individual case. A knowledge of patients' functional reserve is to be necessary
      and all these facts must not be underestimated in preparation of an operation
      type, mainly in wider reconstructions of gastrointestinal tract, at severe
      traumatic conditions, in vascular surgery, neurosurgery, cardiosurgery, urology
      and pediatric surgery.

PMID- 20055308
TI  - [God's work and the contribution of medicine].

PMID- 20055309
TI  - [Known form of the learning process in nursing].

PMID- 20055310
TI  - [Additional coaching towards professional competence].

PMID- 20055311
TI  - [First steps toward a more intense nursing practice].

PMID- 20055312
TI  - [Nursing performance should be turned inwards].

PMID- 20055313
TI  - [Outstandingly competent advice].

PMID- 20055314
TI  - ["I want this to be known for the right reasons"].

PMID- 20055315
TI  - ["The nursing profession fulfills all my expectations"].

PMID- 20055316
TI  - [Not abandoning the opportunity].

PMID- 20055317
TI  - ["Old, disoriented people are not children"].

PMID- 20055318
TI  - [Too much medicine?].

PMID- 20055319
TI  - [A source in the desert].

PMID- 20055320
TI  - [Homophobia is hard to fight].

PMID- 20055321
TI  - [Nurses ignored, resulting in 12 deaths].

PMID- 20055322
TI  - [When a career for women was trampled on....].

PMID- 20055323
TI  - [Pathological beauty].

PMID- 20055324
TI  - Nursing students and clinical instructors' perceptions on the implementation of a
      best practice guideline.
AB  - A university nursing program in Ontario, Canada initiated the process of
      implementing the Registered Nurses' Association of Ontario best practice
      guideline (BPG) on smoking cessation into the curriculum. This study explored
      nursing students' and clinical instructors' perception of the BPG in their
      practice to support faculty in the development of a curriculum that promotes
      smoking cessation and the competencies necessary for graduates to implement
      health promotion skills in practice. Four student nurses and two clinical
      instructors participated in semistructured interviews. Four major themes were
      identified through the data analysis process: personal and professional self,
      health "preaching," developmental perspective and environmental constraints. This
      study presents a curricular model for health promotion practice incorporating the
      components of primary health care, health promotion counseling, smoking cessation
      BPG, and sociopolitical context.

PMID- 20055325
TI  - Engaging millennial learners: Effectiveness of personal response system
      technology with nursing students in small and large classrooms.
AB  - Nurse educators must explore innovative technologies that make the most of the
      characteristics and learning styles of millennial learners. These students are
      comfortable with technology and prefer interactive classrooms with individual
      feedback and peer collaboration. This study evaluated the perceived effectiveness
      of personal response system (PRS) technology in enhancing student learning in
      small and large classrooms. PRS technology was integrated into two undergraduate
      courses, nursing research (n = 33) and junior medical-surgical nursing (n = 116).
      Multiple-choice, true-false, NCLEX-RN alternate format, and reading quiz
      questions were incorporated within didactic PowerPoint presentations. Data
      analysis of Likert-type and open-response questions supported the use of PRS
      technology as an effective strategy for educating millennial learners in both
      small and large classrooms. PRS technology promotes active learning, increases
      participation, and provides students and faculty with immediate feedback that
      reflects comprehension of content and increases faculty-student interaction.

PMID- 20055326
TI  - Preceptors' perspective on recruitment, support, and retention of preceptors.
AB  - In this study, the researchers sought consensus among preceptors of senior
      nursing students about issues key to the preceptors' recruitment, support, and
      retention. A modified Delphi method with two rounds of questionnaires was used
      followed by a focus group to explore issues for which consensus was not reached.
      Preceptors agreed on the importance of personal satisfaction and on a number of
      tangible benefits of being a preceptors such as receiving information on a need
      to-know basis. Topics such as how to help students think critically and how to
      provide constructive feedback also were considered important. Preceptors agreed
      that having students well prepared at the beginning of preceptored experiences
      was important as was receiving a personalized thank you letter to acknowledge
      their work a the end of the experience, two strategies that could help with
      retention.

PMID- 20055327
TI  - Combing scholarship with service: the parent child research collective.
AB  - A significant challenge in academia is effectively dealing with the combined
      faculty roles of teaching, research, and service. Each category involves layers
      of responsibility, which take a toll on time and resources. This article
      describes an initiative developed by faculty in a nursing graduate program using
      the principles of engaged scholarship to meet various goals for faculty and
      students, and provides a specialized service to the community.

PMID- 20055328
TI  - Exploring male students' educational experiences in an associate degree nursing
      program.
AB  - This study explored male students' educational experience in an associate degree
      nursing program. A review of the literature identified a gap in the understanding
      of the experiences of male students in nursing school. Because nursing is a
      profession strongly influenced by societal stereotypes, gender bias, and the
      preponderance of female role models, this qualitative study examined the
      perceptions of men seeking careers in nursing. Interviews with male students
      probed topics such as the reasons men chose nursing as a career, their positive
      and negative experiences, and their satisfaction with their nursing education.
      This research enhanced understanding and promoted nursing knowledge of the unique
      needs of men in nursing education.

PMID- 20055329
TI  - Role-playing in nursing theory: engaging online students.
AB  - The teaching and learning of nursing theory, at all program levels, is
      challenging due to the complexity and abstract nature of its content, the dry
      nature in which the study of theory often is approached, a perception of
      disconnect from practice, and faculty discomfort and avoidance of the subject
      matter. Adapting creative educational strategies to the online environment is an
      ongoing challenge for educators. Role-play relates well to the constructivist
      basis of creating personal meaning based on the individual's experiences. This
      article examines the use of role-play as an educational strategy for teaching
      nursing theory in an online baccalaureate program. In a core professional issues
      course, students adopt the persona of a specific nursing theorist, interacting
      with other "nursing theorists" played by their peers. Student engagement and
      active learning reflect excitement and interest, and course evaluations have been
      extremely positive for this content and method.

PMID- 20055330
TI  - Teaching undergraduate nursing research: a comparison of traditional and
      innovative approaches for success with millennial learners.
AB  - Historically, nursing students have questioned the value of a nursing research
      course and have not appreciated the research-practice link. These are important
      concerns in light of the increasing emphasis on evidence-based nursing practice.
      The purpose of this study was to develop innovative strategies for teaching
      undergraduate nursing research that engage millennial learners and emphasize the
      relationship between evidence-based practice and clinical outcomes. Innovative
      assignments were developed that included interactive learning, group work, and
      practical applications preferred by these learners. Using a Likert scale,
      students' perceived effectiveness of innovative assignments and more traditional
      assignments were compared. Results indicated a preference for active learning
      assignments, reading quizzes, clinical nurse researcher presentations, and
      collaboration with clinical course assignments. By combining traditional
      assignments with innovative strategies and nursing practice applications,
      millennial learners were engaged and able to clearly articulate the value of the
      research-practice link vital to evidence-based nursing practice.

PMID- 20055331
TI  - Collaborative simulation project to teach scope of practice.
AB  - Nursing faculty from three schools of nursing collaborated to develop a
      simulation project to enable nursing students to practice and apply principles,
      leadership, and culturally competent care. A simulated five-bed hospital was
      created where students were assigned to teams to plan and care for these
      patients. After the simulation exercise, students participated in a debriefing
      session in which they reflected on their performance.

PMID- 20055332
TI  - Unilateral Congenital Eyelid Eversion Causing Marked Chemosis in a Newborn.
AB  - A generally healthy male infant was born with unilateral congenital eversion of
      the upper eyelid causing considerable conjunctival injection and chemosis.
      Conservative medical management with topical lubrication and antibiotics resolved
      the condition within a few days. 

PMID- 20055333
TI  - Off-axis digital flash photography: a common cause of artefact leukocoria in
      children.
AB  - Leukocoria, a presenting sign in several significant pediatric ocular conditions,
      can be artefactually produced by off-axis flash photography in healthy eyes. The
      authors demonstrate the conditions needed to produce this phenomenon, which is
      more commonly seen in children due to their larger-sized pupils, photogenicity,
      and frequent off-axis shots. 

PMID- 20055335
TI  - Acquired pediatric blepharoptosis related to linear scleroderma.
AB  - Periocular linear scleroderma coup de sabre has been seen in association with
      blepharoptosis. The authors describe a 4-year-old girl who developed left
      blepharoptosis simultaneously with a remote scalp lesion consistent with linear
      scleroderma coup de sabre. This case is unique in that the scalp lesion was
      distant from the affected eye. 

PMID- 20055336
TI  - Anomalous Medial Rectus Muscle Insertion in a Patient with Nonrefractive Comitant
      Esotropia.
AB  - An 8-year-old girl with nonrefractive comitant estropia revealed the abnormal
      insertion of the medial rectus muscle during muscle recession surgery. Strabismus
      surgeons should be aware of the possibility that anomalous muscles can cause
      unusual types of strabismus. 

PMID- 20055334
TI  - Rhegmatogenous retinal detachment following treatment for retinoblastoma.
AB  - PURPOSE: To elucidate characteristics of rhegmatogenous retinal detachment that
      developed in children who underwent treatment for retinoblastoma and to analyze
      the outcome following vitreoretinal surgery in such clinical settings. METHODS:
      This was a retrospective case series of 9 eyes of 9 patients who underwent
      vitreoretinal surgery for tumor control and retinal reattachment. RESULTS: At the
      time of diagnosis of rhegmatogenous retinal detachment, retinoblastoma was
      regressed in 6 eyes (67%). The retinal detachment involved less than two
      quadrants in 7 eyes (78%) and was caused by an atrophic break in 7 eyes. Seven
      eyes underwent a non-drainage scleral buckling procedure. Three eyes underwent
      vitreous surgery; in 2 of these eyes, tumor excision along with retinectomy using
      melphalan infusion was performed and eventually silicone oil tamponade was used.
      Retinal reattachment was achieved in all eyes with eventual tumor control in 7
      eyes. The median follow-up after retinal reattachment surgery was 24 months.
      CONCLUSION: Rhegmatogenous retinal detachment in treated eyes with retinoblastoma
      is usually caused by an atrophic retinal break. Retinal detachment can be
      repaired successfully in most eyes.

PMID- 20055337
TI  - Factor structure of the geriatric institutional assessment profile's professional
      issues scales.
AB  - The Geriatric Institutional Assessment Profile (GIAP) is a self-administered
      survey of hospital nurses, designed to assess a hospital's readiness to implement
      geriatric programs. A sample of 2,211 direct care RNs in 24 hospitals was
      randomly split in half to analyze the Geriatric Professional Issues scales of the
      GIAP, using one sample for exploratory factor analysis and one for confirmatory
      factor analysis. An exploratory factor analysis of the six Geriatric Professional
      Issue scales (staff disagreement, staff/family/patient disagreement, use of
      geriatric services, perceived legal vulnerability, perceived upsetting behaviors,
      and burden of upsetting behaviors) demonstrated very good internal consistency
      both as a whole (Cronbach's alpha coefficient = 0.90) and as individual factors
      (0.94, 0.91, 0.92, 0.89, 0.85, and 0.81, respectively). The six factors were
      validated in a half randomly selected sample, with a root-mean-square error of
      approximation fit index of 0.07 and the normed and non-normed fit indices both
      0.8, all indicating adequate fit of the six-factor model.

PMID- 20055338
TI  - Identifying and validating the components of nursing practice models for long
      term care facilities.
AB  - Nursing practice models (NPMs) provide the framework for the design and delivery
      of nursing care to residents in long-term care (LTC) facilities and characterize
      the manner in which nursing staff assemble to accomplish clinical goals. The
      purpose of this study was to identify and validate the distinctive components of
      NPMs in LTC facilities and develop an instrument to describe and evaluate NPMs in
      such settings. The study included validation of the NPM components through a
      literature review and focus groups with nursing staff from LTC facilities;
      development and modification of the Nursing Practice Model Questionnaire (NPMQ);
      and examination of the validity and reliability of the NPMQ through pilot testing
      in 15 LTC facilities with 508 nursing staff. Five factors--decision making,
      informal continuity of information, formal continuity of information, continuity
      of care, and accountability--comprise the five subscales of the NPMQ, a 37-item
      questionnaire with established respectable validity and reliability.

PMID- 20055339
TI  - Early failures in unicondylar arthroplasty.
AB  - Unicondylar arthroplasty has reemerged as an option for isolated compartment knee
      arthritis. We have noticed an increase in the need for early revision of this
      construct at our revision center. This study sought to determine if the need for
      unicondylar revision has increased over time and what factors may have led to
      early failure. Revision total knee arthroplasties (TKAs) performed between 1990
      and 1999 (period 1) were compared to TKAs performed between 2000 and 2008 (period
      2). The prevalence of unicondylar revision, time to failure, and reasons for
      failure were calculated. Between 1990 and 1999, 425 revision TKAs were performed,
      7 of which were uni-revisions (1.6%). These had been in place an average of 169
      months (range, 12.9-478.6 months). Between 2000 and 2008, 744 revision TKAs were
      performed, 43 of which were uni-revisions (5.8%). These had been in place an
      average of only 36 months (range, 4.2-159.5 months). The dominant reasons for
      failure in period 1 included poly wear and loosening. Reasons for failure in
      period 2 were variable but included a number of technical errors. Early failure
      of unicondylar arthroplasty appears to be on the rise. Acknowledging that these
      patients came from an unknown pool, we are concerned that market pressure may
      have led to inappropriate patient selection and that surgical inexperience with
      this procedure may have led to the technical problems noted in period 2. Patients
      should be apprised of the possibility of early revision with this procedure.

PMID- 20055340
TI  - Comparison of revision rates in bone-patella tendon-bone autograft and allograft
      anterior cruciate ligament reconstruction.
AB  - This study compared the revision rates after autograft and allograft bone-patella
      tendon-bone anterior cruciate ligament (ACL) reconstruction. All bone-patella
      tendon-bone ACL reconstructions performed by a single surgeon between January
      2000 and December 2006 were identified by retrospective chart review. Two hundred
      twenty-three patients met the inclusion criteria and 173 patients were available
      for follow-up. One hundred forty-two patients underwent bone-patella tendon-bone
      autograft reconstruction, and 31 patients underwent bone-patella tendon-bone
      allograft reconstruction. At a mean follow-up of 49 months (range, 11-91 months),
      revision rates were 0.7% (1/142) in the bone-patella tendon-bone autograft group
      versus 9.7% (3/31) in the bone-patella tendon-bone allograft group (P=.02).
      Subjective International Knee Documentation Committee (IKDC) scores of nonrevised
      (surviving) grafts in the bone-patella tendon-bone autograft group were 98.3
      versus 95.2 in the bone-patella tendon-bone-allograft group (P=.0006). Tegner
      scores of nonrevised grafts in the bone-patella tendon-bone-autograft group were
      6.2 vs 6.5 in the bone-patella tendon-bone-allograft group (P=.03). Fourteen of
      the 31 (45%) allografts were irradiated and all failures occurred in irradiated
      grafts. When irradiated grafts were excluded, no difference in revision rates was
      found. Anterior cruciate ligament reconstruction with the use of bone-patella
      tendon-bone allografts is associated with a higher revision rate when compared to
      bone-patella tendon autograft reconstruction. In addition, when comparing
      surviving grafts, the subjective IKDC scores are higher in the autograft group.
      When irradiated grafts are excluded, no difference in revision rates was found.
      Surgeons should be aware of the higher revision rate associated with allograft
      ACL reconstruction when counseling patients on graft options.

PMID- 20055341
TI  - Evaluation of the modified Elmslie-Trillat procedure for patellofemoral
      dysfunction.
AB  - The goal of this study was to evaluate the Elmslie-Trillat procedure for
      recurrent patellar dislocation, patellofemoral pain (with extensor mechanism
      malalignment), or a combination of both. Thirty-two patients underwent the
      modified Elmslie-Trillat procedure, consisting of a lateral retinacular release
      and medialization of the tibial tuberosity for recurrent patellar dislocation,
      patellofemoral pain, or both. Twenty-nine of 32 patients were available for
      follow-up. All patients were evaluated clinically and radiologically. Subjective
      scores were evaluated using the Cox grading system and objective scores using
      Fulkerson's functional knee score. Average patient age was 33 years. Mean follow
      up was 45 months. Subjectively, using the Cox grading system, 10 patients (34%)
      had an excellent result, 8 (28%) had a good result, 8 (28%) had a fair result,
      and 3 (10%) had a poor result. All patients with patella dislocation had an
      excellent or good subjective result, while only 3 patients (34%) with the primary
      symptom of patellofemoral pain with extensor mechanism malalignment and 4
      patients (44%) with a combination of both symptoms had a good or excellent
      result. Mean Fulkerson's functional knee score was excellent for patients with
      dislocation only, and fair for those with only pain or both pain and dislocation.
      The congruence angle was corrected in all patients with this technique. There
      were no further dislocations in our series. Two patients required hardware
      removal. The Elmslie-Trillat procedure is a good surgical option for treatment of
      recurrent patella instability following failed conservative therapy. However, the
      results are not as favorable for patients with patellofemoral pain without
      instability.

PMID- 20055342
TI  - Floating knee injuries: a high complication rate.
AB  - Floating knee injuries are usually associated with complications and mortality,
      regardless of the treatment regimen. Orthopedic surgeons typically recommend
      various treatment regimens, especially aggressive and early stabilization of both
      femoral and tibial fractures. Some authors have reported that the complication
      and mortality rates remain high regardless of the treatment regimen used. The
      purpose of this retrospective study was to review the long-term results of
      treatments for floating knee injuries performed at our institution, and also to
      calculate the distribution of fracture types within patient age groups and the
      association with complications related to floating knee injury. We
      retrospectively reviewed medical records and radiographs of 419 floating knee
      injuries treated for postoperative complications from November 1987 to April
      2003. Of the 419 patients with floating knee injuries, 104 (24.8%) developed
      complications. The result showed that the complication rate was associated with
      fracture type (open fracture [32.2%; P<.001], Fraser type IIc [36.8%; P<.001],
      tibial plateau [28.6%; P=.037], and distal tibia [28.6%; P=.035]). This study
      revealed that the complication rate associated with floating knee injuries
      remained high, regardless of the treatment regimen used. Surgeons should focus on
      reducing complications while treating floating knee injuries.

PMID- 20055343
TI  - Incomplete seating of a metal-backed alumina liner in ceramic-on-ceramic total
      hip arthroplasty.
AB  - Metal-backed modular ceramic bearing systems using a recessed alumina liner in a
      titanium sleeve were developed to decrease ceramic chipping or fracture due to
      femoral neck impingement after total hip arthroplasty (THA). However, malseating
      of the metal-backed ceramic liner has recently been described. The goal of this
      study was to assess the prevalence, etiology, and clinical relevance of this
      event. Between 2005 and 2008, 51 consecutive patients (61 hips) underwent THA
      with a metal-backed alumina liner housed in a titanium shell. The metal-backed
      ceramic liner was aligned, seated, and impacted into the shell, and satisfaction
      in terms of liner stability and seating was confirmed intraoperatively.
      Postoperative assessment of seating was assessed with standard radiographs. Liner
      seating was classified as well seated, suspicious, or malseated. Seven liners
      (11.5%) were found to be malseated and 4 (6.5%) were considered suspicious.
      Radiographically, there was a gap between the liner and the shell located
      inferomedially in 4 patients and superolaterally in 3 patients. Two liners
      subsequently seated at 1 and 3 months postoperatively, respectively. No
      dislodgement, failures, or adverse events were identified. There were no revision
      surgeries. The significant percentage of malseated liners were potentially
      attributed to poor exposure, bony/soft tissue interposition, and surgeon learning
      curve.

PMID- 20055344
TI  - Clinical significance of the heterotopic ossification after total hip
      arthroplasty.
AB  - Heterotopic ossification represents one of the most frequent complications
      following any type of hip arthroplasty. However, disagreement exists regarding
      the clinical significance of heterotopic ossification after total hip
      arthroplasty (THA). This study evaluated the effect of different grades of
      heterotopic ossification on range of hip motion, pain, and the clinical outcome
      in patients after THA. The study included 198 patients with primary THA because
      of unilateral hip osteoarthritis, followed for a minimum of 1 year after THA.
      Diagnosis and classification of heterotopic ossification according to Brooker was
      achieved on anteroposterior radiograph of the hips 1 year postoperatively. The
      clinical outcome was assessed at 1-year follow-up with the use of the Harris hip
      score. Pain was assessed as the pain component of the Harris hip score. Hip range
      of motion was measured passively in the lying position with a goniometer and
      recorded in degrees according to the method suggested by the American Academy of
      Orthopaedic Surgeons 1988. The incidence of heterotopic ossification was 47% and
      the incidence of severe ossification was 11%. The severe heterotopic ossification
      significantly reduced clinical outcome, overall range of hip motion and certain
      components such as flexion, abduction and external rotation, but had no
      significant effect on pain, while the lower degree of ossification did not
      significantly influence the clinical outcome, hip motion and pain. This study has
      shown that only severe heterotopic ossification is of clinical significance.

PMID- 20055345
TI  - The effect of tranexamic acid on reducing blood loss in cementless total hip
      arthroplasty under epidural anesthesia.
AB  - Total hip arthroplasty (THA) is associated with high intraoperative and
      postoperative blood loss. Antifibrinolytic drugs have been used to minimize the
      potential risks of bleeding and blood transfusion. Studies on the effect of
      tranexamic acid on decreasing blood loss in THA have revealed interesting
      results, but most have focused on cemented THA. Yet its benefits in THA,
      especially in cementless THA, have not been proved. We conducted a prospective
      double-blind randomized controlled study on 64 patients who were candidates for
      cementless THA under epidural anesthesia between 2006 and 2008. Patients were
      randomly assigned into study and control groups. Patients in both groups were
      well matched regarding preoperative characteristics. Five minutes preoperatively
      32 patients of the study and control groups received 15 mg/kg tranexamic acid or
      normal saline intravenously respectively. Our findings showed a significantly
      smaller decrease in 6- and 24-hour postoperative hemoglobin levels, less
      intraoperative and postoperative bleeding, and less need for allogenic blood
      transfusion in the tranexamic acid group. Our results also revealed a higher mean
      of 6- and 24-hour hematocrit level and shorter hospital stay in the tranexamic
      acid group compared to the control group, which were not statistically
      meaningful. In our study no thromboembolic event was seen; except 1 patient in
      the control group. Our study showed that administering tranexamic acid before the
      start of cementless THA under epidural anesthesia can reduce intraoperative and
      postoperative bleeding as well as need for blood transfusion.

PMID- 20055346
TI  - A biomechanical comparison of three different lateral tibia locking plates.
AB  - The purpose of this study was to determine how well laterally placed modern tibia
      locking plates used in the treatment of Schatzker V tibial plateau fractures
      would uphold the medial plateau during axial loading. Fifteen third generation
      Sawbone tibias were obtained and an osteotomy was cut beneath the medial plateau
      to recreate Schatzker V type plateau fractures. Three groups were created (n=5
      per group). Each group was plated with either a Synthes 4.5-mm LCP proximal
      tibial plate, a Zimmer NCB proximal tibia plate, or a DePuy Polyax tibial plate.
      A vertical load was applied over the medial plateau using an Instron
      servohydraulic test machine. Load measurements were analyzed at 2 and 3 mm of
      subsidence as well as load to failure. Failure was defined as closure of the
      wedge osteotomy or the medial condyle collapsing. A statistical difference was
      noted between the 2 plates from Synthes and DePuy and the plate from Zimmer with
      load carried at 2 and 3 mm of subsidence (Synthes 640.4 N & 943.7 N, Depuy 607.4
      N & 891.0 N, Zimmer 459.7 N & 643.2 N). At failure, DePuy (2051.2 N) was
      statistically stronger than both Synthes (1724.8 N) and Zimmer (1724.8 N). The
      Synthes and DePuy plates both held up better than the Zimmer plate at 2 and 3 mm
      of subsidence. Despite this fact, all plates tested held up well above
      physiological forces of full and partial weight bearing and therefore would be
      appropriate for the treatment of Schatzker V type tibial plateau fractures.

PMID- 20055347
TI  - Use of the Gartland classification system for treatment of pediatric
      supracondylar humerus fractures.
AB  - The extension-type pediatric supracondylar humerus fracture accounts for nearly
      two-thirds of all pediatric hospitalizations due to elbow trauma. The Gartland
      classification guides the standard of care for treatment of this entity. Type I
      injuries are treated with cast immobilization while type II and III injuries are
      treated operatively. The reported interobserver reliability ranges from moderate
      to full agreement, which is on par with other frequently referenced
      classification systems such as Lauge-Hansen for adult ankle fractures. In this
      study, 4 fellowship-trained pediatric orthopedic surgeons reviewed radiographs of
      72 pediatric supracondylar fractures and classified them based on Gartland's
      system. They recommended their preferred treatment of cast immobilization for
      type I fractures and of closed reduction and pinning in the operating room for
      type II and type III fractures. The interobserver and intraobserver reliability
      for each set of radiographs was then analyzed. There was moderate agreement
      comparing all fractures and comparing types I and II fractures, while there was
      full agreement for type III fractures. There was full agreement for the
      intraobserver reliability. The preferred treatment (casting vs operative
      intervention) differed in 35% of patients, if based on the fracture
      classification.

PMID- 20055348
TI  - Two-stage shoulder reconstruction for active glenohumeral sepsis.
AB  - In some circumstances, two-stage reconstruction is recommended for the treatment
      of glenohumeral sepsis. This study retrospectively reviewed the results in 25
      patients after this treatment. Pain was the only consistent preoperative symptom,
      found in 95% of patients. The most common infecting organisms were coagulase
      negative Staphylococcus in 8 cases, Proprionibacterium acnes in 7, and
      methicillin-sensitive Staphylococcus aureus in 3. Outcomes were reviewed in 21
      patients with 2-year minimum follow-up, at an average 4.1 years. Infection was
      eradicated in 18 of 21 shoulders. Success was related to the specific infecting
      organism, as all failures were among shoulders infected with Proprionibacterium
      (P=.0198). Pain was typically relieved, with a mean visual analog pain score of
      1.67 at follow-up. Motion was similarly improved, with flexion increased to 100.9
      degrees (P<.001), abduction to 93.6 degrees (P<.001), and external rotation 32.6
      degrees (P=.0012). Two-stage shoulder reconstruction for infection is typically
      effective for curing the infection and improving pain and motion; however,
      function tends to remain limited.

PMID- 20055349
TI  - Neurovascular risks of anteroinferior clavicular plating.
AB  - Anteroinferior plating has been described for internal fixation of clavicular
      fractures, citing improved bicortical fixation, less hardware prominence, and
      safer drill trajectories compared with other plate configurations. This anatomic
      study defined structures at risk during anteroinferior clavicular plating. Four
      paired cadaveric specimens (8 clavicles) from ages 75 to 93 years were
      systematically dissected. Using the screw paths associated with an anteroinferior
      plate (anteroinferior to superoposterior), the distance from the posterior
      clavicle cortex to the nearest vital structure was measured at 5 different
      positions along the clavicle. In the medial half of the clavicle, the subclavian
      artery is in closest proximity to the clavicle, measuring, on average, 22.95 mm
      and 15.10 mm at point A and B. At the lateral three-fifths point of the clavicle
      (point C), the brachial plexus is 12.76 mm from the posterior clavicle and is
      more at risk than the subclavian artery. Lateral to the three-fifth point of the
      clavicle, there were no vital structures that could be injured by overdrilling.
      Our results suggest that more care should be observed with placement of screws in
      the medial half of the clavicle where subclavian artery damage is more likely.

PMID- 20055350
TI  - The strength and effects of humeral rotation on single- versus double-row repair
      techniques in small rotator cuff tears.
AB  - With advanced surgical techniques, instrumentation, and implants, arthroscopic
      rotator cuff repair has become increasingly popular. As the techniques continue
      to evolve, so do the methods by which the repairs are tested. Cyclic loading has
      shown to better replicate postoperative motion after cuff repair. Recently,
      cyclic loading with dynamic external rotation has been studied for large rotator
      cuff repairs. Our study applies this concept to small, isolated supraspinatus
      tears, comparing single- vs double-row repair techniques. A 1.5-cm rotator cuff
      tear was created in cadaveric specimens and repaired with single-and double-row
      repair techniques. With cyclic loading and dynamic external rotation, gap
      formation and ultimate pullout strength were determined and found to be
      equivalent. This study demonstrates no significant difference in single- vs
      double-row repairs for small, isolated supraspinatus tears when tested with
      cyclic loading and dynamic external rotation.

PMID- 20055351
TI  - Insertional footprint anatomy of the pectoralis major tendon.
AB  - Correct anatomical repair of pectoralis major tendon injuries requires accurate
      identification of the humeral insertion site. In the absence of residual fibers
      at the insertion, proper placement requires knowledge of the anatomic
      relationships in the proximal humerus. This anatomic study attempts to measure
      these relationships and the dimensions of the insertional footprint to assist in
      surgical repair and reconstruction. Six matched pairs of cadaver proximal humeri
      were examined. All specimens were found to be in good condition and none were
      excluded. The proximal to distal length and maximum width of the pectoralis major
      tendon were measured at the humeral insertion with a digital caliper. The
      distance from the superomedial corner of the greater tuberosity to the superior
      aspect of the tendon insertion was also measured. The mean proximal to distal
      dimension of the pectoralis major insertion was 72.3+/-12.3 mm. The mean maximal
      thickness at the humeral insertion was 1.4+/-.2 mm. The distance from the
      superomedial corner of the greater tuberosity to the bony tendon insertion was
      42.2+/-8.5 mm. The anatomic location of the humeral insertion of the pectoralis
      major tendon can be located in repair of pectoralis tendon injuries by
      referencing the superomedial corner of the greater tuberosity and the lateral lip
      of the bicipital groove. Findings in the present study will improve knowledge of
      the surgical anatomy relevant to repair and reconstruction of the pectoralis
      major tendon.

PMID- 20055352
TI  - Balloon kyphoplasty in the treatment of osteoporotic vertebral compression
      fracture nonunion.
AB  - Patients with nonunion of osteoporotic vertebral compression fractures that are
      refractory to conservative treatments have persistent back pain, progressive
      vertebral body collapse and kyphosis, and mobility of the fracture. Although many
      previous reports have reported vertebral compression fractures treated by balloon
      kyphoplasty, few data is available on using this method to treat nonunion of
      vertebral compression fractures. This study evaluated the therapeutic potential
      of balloon kyphoplasty in the treatment of nonunion of osteoporotic vertebral
      compression fractures. Twenty-one patients with nonunion of osteoporotic
      vertebral compression fractures were treated with balloon kyphoplasty. The
      criteria for diagnosis of nonunion osteoporotic vertebral compression fractures
      included the following: (1) history of pain for at least 6 months at the fracture
      site; (2) low T1- and high T2-signal on magnetic resonance images; (3) widening
      of fracture line on routine radiographs; and (4) movement of the endplate and
      changes of anterior vertebral heights on hyperextension radiographs. All patients
      were followed for 9 to 33 months postoperatively (mean 25 months). Statistically
      significant improvements in the mean postoperative anterior and middle vertebral
      body heights were observed compared with preoperative values. There was also
      statistically significant improvement in the mean values for Cobb's angle, pain
      (visual analog scale), and the Oswestry Disability Index at the postoperative
      assessment compared with the preoperative assessment. No statistically
      significant differences were noted between the postoperative and final follow-up
      assessment in any of the evaluated efficacy measures. The study suggests that
      balloon kyphoplasty is an effective technique to treat nonunion of osteoporotic
      vertebral compression fractures.

PMID- 20055353
TI  - Optimal transport time and conditions for cartilage tissue samples and expanded
      chondrocyte suspensions.
AB  - For autologous chondrocyte implantation, the chondral tissue obtained is
      transferred from the operating room to the laboratory using specialized carrier
      systems within 24 hours. Similar expenses are used for the transport of cultured
      chondrocytes. The purpose of this study was to find the optimal temperature, size
      of tissue, and time that the chondrocytes can stand without losing viability and
      proliferative capacity. Fresh calf cartilage was harvested and divided into 24
      groups. Half of the samples were diced into 1- to 2-mm(3) pieces. All 12 groups
      were kept at either 4 degrees C, 25 degrees C, or 37 degrees C for 1, 3, 5, or 7
      days and were seeded for cell culture. Times to reach confluence values were
      compared. Produced cell suspensions were grouped similarly and tested similarly.
      Neither the temperature nor the waiting days caused any difference in the
      proliferative capacity of the cells. Diced tissues yielded a shorter time to
      reach confluence values. Chondral tissue obtained from the patient can be
      transferred to the laboratory at temperatures ranging from 4 degrees C to 37
      degrees C in up to 7 days. These conditions did not affect the proliferative
      capacity or the viability of the chondrocytes. Dicing the tissue prior to
      transport will shorten total culturing time. The expanded cell suspensions should
      be transferred at temperatures from 4 degrees C to 25 degrees C within 3 days.
      Specialized carrier systems to get the chondral tissue from the operating room to
      the laboratory and to take the expanded chondrocytes back to the operating room
      within hours may not be necessary.

PMID- 20055354
TI  - Arthroscopic treatment of localized synovial chondromatosis of the posterior knee
      joint.
AB  - Synovial chondromatosis is an uncommon, benign neoplastic process typically
      affecting adult men and most commonly involving the knee, hip, and elbow joints.
      Intra-articular primary synovial chondromatosis in the knee joint may be
      localized or generalized. The symptoms associated with localized synovial
      chondromatosis may include diffuse pain, swelling, restricted motion, crepitus
      with symptoms of locking and giving way, and posteromedial tenderness mimicking
      medial meniscus tear. Diagnosis is usually established with magnetic resonance
      imaging (MRI) and confirmed by histological examination. To our knowledge,
      synovial chondromatosis of the knee joint in the posteromedial corner has not
      been reported in the literature.

PMID- 20055355
TI  - Metal-on-metal hip resurfacing in patients with pigmented villonodular synovitis:
      a report of two cases.
AB  - Pigmented villonodular synovitis (PVNS) of the hip joint is a rare and benign
      tumor of the synovia. This local, aggressive, proliferative disorder of the joint
      synovial membrane can lead to secondary osteoarthritis and represents a small
      percentage of all patients undergoing total hip replacement (THR). Because of the
      usually young age of the patients undergoing THR for PVNS, a resurfacing
      arthroplasty of the hip appears as a beneficial treatment option due to its bone
      conserving nature, good joint stability, and ability to easily convert to a THR
      if needed. This article describes 2 cases of metal-on-metal hip resurfacing in
      patients with pigmented villonodular synovitis. In patient 1, PVNS was suspected
      on radiographs but confirmed only after removal of a mass of thick, grey-brown
      spotted synovia. A complete synovectomy was performed prior to hip resurfacing.
      Seven years postoperatively, radiographs show secure fixation of the components
      with no radiolucencies. In patient 2, arthroscopy of the hip joint had been
      performed 3 months prior, but PVNS had not been diagnosed. Pigmented villonodular
      synovitis was confirmed during the operation when incising a yellowish nodular
      mass protruding from the capsule. Granuloma was also found in the inferior and
      anterior part of the acetabulum. Four years postoperatively, the patient exhibits
      excellent clinical and radiographic results. Complete surgical removal of all
      tissue affected with PVNS is the key to a successful resurfacing, which is
      otherwise technically similar to resurfacing in patients with other etiologies.
      The mid-term results of the 2 presented cases are satisfying and show the
      potential of the resurfacing technique for young patients with PVNS of the hip.

PMID- 20055356
TI  - Solitary osteochondroma of the proximal femur and femoral acetabular impingement.
AB  - Although osteochondromas can be present within the context of multiple hereditary
      exostosis, these tumors are overwhelmingly found as isolated lesions. Increased
      exostotic load associated with multiple hereditary exostosis can lead to limb
      length discrepancy, increased femoral anteversion, valgus angulation, and
      acetabular dysplasia. Despite these observations, the relationship of more common
      isolated exostoses near the proximal femur and their role in femoral acetabular
      impingement has never been depicted. Although solitary osteochondromas have been
      linked with bursal inflammation and pain, compression on neurovascular
      structures, and malignant degeneration, they have not previously been associated
      with femoral acetabular impingement. This article presents a novel case of a
      proximal femoral osteochondroma of the greater trochanter leading to the
      development and associated symptoms and radiographic findings consistent with hip
      impingement. A 24-year-old man presented with groin and lower extremity pain
      thought to be due to an exostosis of the proximal femur. Following surgical
      excision and persistence of anterior groin pain, the patient was found to display
      a presentation and radiographic findings consistent with femoral acetabular
      impingement. He successfully underwent a hip arthroscopy, femoroacetabular
      osteochondroplasty, and labral repair. Postoperatively, his symptoms improved
      significantly, and he returned to normal activity. The presence of a proximal
      femoral exostosis can be associated with the development of femoral acetabular
      impingement. Awareness of this relationship may lead to a better understanding of
      patient symptoms and expectations associated with treatment.

PMID- 20055357
TI  - Spindle-cell hibernoma: a clinicopathologic comparison of this new variant.
AB  - Spindle-cell hibernoma is 1 of 4 histologic variants of hibernomas, which are
      rare lipomatous tumors distinguished from other lipomas by their brown fat
      component. This article presents a case of a spindle-cell hibernoma that
      developed in the groin of a 58-year-old man, and is 1 of only 5 known cases of
      spindle-cell hibernoma published in the scientific literature. Minimal
      information is available regarding the clinicopathologic characteristics of the 4
      hibernoma variants: typical, lipoma-like, myxoid, and spindle-cell. Spindle-cell
      hibernoma is believed to be the rarest variant, accounting for approximately 2%
      of hibernomas. The spindle-cell variant predominantly develops in the fourth and
      fifth decades, with an average age at diagnosis of 42.5 years (range, 28-59
      years). It has a male predilection of 4:1. Previously reported only in the
      posterior neck and scalp, the groin is now added to the sites of spindle-cell
      hibernoma occurrence. Our patient's tumor demonstrated low-attenuation on
      computed tomography and contained moderately-attenuating internal septae.
      Histologically, in addition to the multivacuolated brown fat component common to
      all hibernomas, spindle-cell hibernoma has a spindle-cell element without
      vacuolization that is CD34 positive. No prior treatment details are available on
      this particular variant. Our patient was treated by marginal excision and was
      disease free through 13 months of follow-up.

PMID- 20055358
TI  - Pathologic correlation of posterior ligamentous injury with MRI.
AB  - This article describes 2 cases of spinal trauma in which diagnostic magnetic
      resonance imaging (MRI) was correlated with histopathology for diagnosis of a
      posterior ligamentous complex injury. Spine fractures are common and represent up
      to 16% of traumatic fractures. Diagnostic imaging currently involves plain films
      and computerized tomography, but MRI is being used with increasing frequency. The
      definition of neurologic tissue injury has had substantial documentation in the
      spinal literature. Clinically, posterior ligamentous complex injury has been
      associated with facet disruption, gapping of the spinous processes, and
      significant kyphosis. Assessment of spinal stability in the spine trauma
      population is based significantly on the assumed disruption or integrity of the
      posterior ligamentous complex. High signal intensity in the area of the
      ligamentum flavum and interspinous ligament on fat-saturated T2 MRIs has been
      associated with the clinical finding of interspinous ligament disruption noted at
      surgical exploration. Magnetic resonance imaging in spine trauma is widely
      accepted despite a paucity of data addressing its histopathologic accuracy. To
      our knowledge, histopathologic correlation of MRI of ligamentous injuries has not
      been reported.

PMID- 20055359
TI  - Prevalence of Coxiella burnetii antibodies in wild ruminants in Kavecany zoo,
      Kosice, eastern Slovakia.
AB  - Coxiella burnetii is an obligate intracellular agent that causes Q fever in
      humans and animals. The most important reservoirs of C. burnetii in nature are
      small wild rodents, but infection was also demonstrated in other animals,
      including ruminants. Samples of blood were obtained from 4 mouflons, 60 fallow
      deer, 9 Cameroun goats, 8 Carpathian goats, and 8 Cameroun sheep living in a zoo.
      Antibodies to phase I and phase II C. burnetii antigens were determined in sera
      by ELISA. Antibody titres were detected in the range 1:100-1:200. The serum
      prevalence of phase II and phase I antibodies to C. burnetii antigens was 25 %
      and 0% in mouflons, 70 % and 0% in goats, 37.5 % and 12.5 % in sheep and 28.3 %
      and 5 % in fallow deer, resp. Serologic diagnosis of Q fever in animals can be
      difficult. Some animals may shed C. burnetii and pose a risk for infection prior
      to the development of antibodies, and some infected animals never seroconvert.
      The employed ELISA test is a very sensitive assay for C. burnetii, but it is also
      a labour intensive method and therefore not routinely available.

PMID- 20055360
TI  - Some evidence of scaling behavior in the relaxation dynamics of aqueous polymer
      solutions.
AB  - The structural relaxation behavior of aqueous solution of poly(ethylene glycol)
      and methoxy-capped poly(ethylene glycol), both of mean molecular mass 400 g/mol,
      is investigated by Brillouin scattering experiments. In both cases non-Debye
      relaxation processes have been detected, proceeding on the picosecond time scale.
      The average values of the detected relaxation time distributions fail to follow
      the simple Arrhenius behavior. The temperature evolution of the relaxation time
      is adequately fitted using the phenomenological Vogel-Fulcher-Tamman (VFT) model.
      In spite of the different temperature and concentration dependences observed for
      the two kinds of systems, with the exception of the highest samples
      concentrations, a unique scaling behavior has been found for the real and
      imaginary parts of the loss modulus plotted as a function of the reduced inverse
      temperature, T(0)/T, T(0) being the VFT arrest temperature. The presence of a
      unique scaling law in aqueous solutions of polymers characterized by different
      end groups suggests the establishment of similar hydrogen-bonded local
      structures. Within this scenario, water acts as a stabilizer and plays the main
      role bridging neighboring polymer chains. The possible physical interpretation of
      the obtained fit parameters is discussed, and the results are compared with other
      literature findings.

PMID- 20055361
TI  - Formation, characterization, and thermal degradation behavior of a novel
      tricomponent aggregate of beta-cyclodextrin, ferrocene, and polypropylene glycol.
AB  - A tricomponent aggregate PPG-Fc-beta-CD formed by polypropylene glycol (PPG),
      ferrocene (Fc), and beta-cyclodextrin (beta-CD) was obtained and characterized by
      a series of physical methods, such as (1)H nuclear magnetic resonance, flame
      atomic absorption spectrometry, high performance liquid chromatography, UV-vis
      absorption spectroscopy, thermogravimetry, and gas chromatography coupled to time
      of-flight mass spectrometry. First, the tricomponent aggregate exhibited a
      component ratio of 1:28:32 (PPG/Fc/beta-CD) in the solid state, and showed a
      completely different order in thermal stability when compared with beta-CD: under
      a nitrogen atmosphere, beta-CD > PPG-Fc-beta-CD, and in a vacuum, PPG-Fc-beta-CD
      > beta-CD. Second, the appearance of two peculiar points p and q at the end of TG
      curve of the aggregate gave a strong impression that the degradation rate further
      increased after the sharp decomposition of the aggregate reached point p and the
      amount present in the residual fraction at point q about 780.0 K was lower than
      1%, both of which were rather different from those reported previously. This
      finding implied that the molecular assembly resulting from the binding
      interaction among Fc, PPG, and beta-CD induced more efficiently the degradation
      of each of them. Third, an interesting phenomenon was found that the order of
      thermal release of the three assembled components in PPG-Fc-beta-CD was Fc > beta
      CD > PPG. Results of this study provide some insight into an initial attempt to
      construct a supramolecule among a polymer, a coordination compound, and an
      organic compound.

PMID- 20055362
TI  - Estimation of kinetic parameters when modifiers are bound in enzyme-catalyzed
      reactions.
AB  - Modifiers of enzyme-catalyzed reactions can have various types of effects on the
      velocity, but the most important effect is that they provide multiple pathways to
      products. The rapid-equilibrium kinetic effects of modifiers are explored for the
      enzyme-catalyzed reaction A --> products. When a single molecule of modifier X is
      bound, the mechanism involves three independent equilibrium expressions and two
      rate constants. But when two molecules of X are bound are bound in two reactions,
      there are five independent equilibria and three paths to products. The advantages
      of using a computer to derive rapid-equilibrium rate equations are that more
      complicated rate equations can be derived and the kinetic parameters can be
      estimated using the minimum number of velocity measurements. The mechanism with
      three paths to products is of special interest because the effects of
      cooperativity can be studied. Thermodynamic cycles can be used to estimate
      additional kinetic parameters.

PMID- 20055363
TI  - Structural and energetic determinants of thermal stability and hierarchical
      unfolding pathways of hyperthermophilic proteins, Sac7d and Sso7d.
AB  - Identification of the structural and energetic determinants responsible for
      enhancing the stability of proteins is crucial. Hyperthermophilic proteins are
      naturally occurring proteins that exhibit high thermal stability and are good
      candidates for the investigation and understanding of structure-stability
      relationships. Sac7d from Sulfolobus acidocaldarius and Sso7d from Sulfolobus
      solfactaricus are two homologous hyperthermophilic proteins that were shown to be
      quite stable at high temperatures. Molecular dynamics simulations at the
      nanosecond time scale at different temperatures were performed to examine the
      factors affecting their stability. The three-dimensional structures of these
      proteins were observed to be similar to the experimental structure at 300 and 360
      K but were found to undergo denaturation at 500 K. Both proteins exhibit similar
      unfolding pathways that correlates well with the calculated intermolecular
      interaction energies. The differential dynamic behaviors of these molecules at
      different temperatures were examined. Structural and energetic analysis of the
      contributions of salt bridges indicates a stabilizing effect at higher
      temperatures. However, the lifetimes of the salt bridges were found to be quite
      short, and several new salt bridges formed at 500 K supporting previous studies
      that the desolvation penalty due to the formation of salt bridges decreases at
      elevated temperatures. Hydrophobic interactions, which decrease with increase in
      temperature, were also found to be crucial in the stability of these proteins.
      Overall, the study shows that a balance among the salt bridge interactions,
      hydrophobic interactions, and solvent properties is primarily responsible for the
      high thermal stability of this class of proteins.

PMID- 20055364
TI  - Resonance effect on self- and inter-association hydrogen bonding interaction of
      polymer blend.
AB  - A comparative study of three poly(methacrylamides) containing different N
      substitutions was carried out in order to obtain a better understanding of the
      resonance effects on the inter-association and self-association hydrogen bonding
      interactions in polymer blends. DSC and solid-state NMR analyses are employed to
      study the relative miscibility of these three binary blends, indicating that the
      PNPAA/P4VP blend has a better miscibility than the PNMAA/P4VP and PNCHAA/P4VP
      blends, because the resonance characteristic of the aromatic ring in PNPAA
      enhances the inter-association hydrogen bonding with P4VP based on FTIR and solid
      state NMR analyses.

PMID- 20055365
TI  - Guest rotations within a capsuleplex probed by NMR and EPR techniques.
AB  - With the help of (1)H NMR and EPR techniques, we have probed the dynamics of
      guest molecules included within a water-soluble deep cavity cavitand known by the
      trivial name octa acid. All guest molecules investigated here form 2:1
      (host/guest) complexes in water, and two host molecules encapsulate the guest
      molecule by forming a closed capsule. We have probed the dynamics of the guest
      molecule within this closed container through (1)H NMR and EPR techniques. The
      timescales offered by these two techniques are quite different, millisecond and
      nanosecond, respectively. For EPR studies, paramagnetic nitroxide guest molecules
      and for (1)H NMR studies, a wide variety of structurally diverse neutral organic
      guest molecules were employed. The guest molecules freely rotate along their x
      axis (long molecular axis and magnetic axis) on the NMR timescale; however, their
      rotation is slowed with respect to that in water on the EPR timescale. Rotation
      along the x axis is dependent on the length of the alkyl chain attached to the
      nitroxide probe. Overall rotation along the y or z axis was very much dependent
      on the structure of the guest molecule. The guests investigated could be
      classified into three groups: (a) those that do not rotate along the y or z axis
      both at room and elevated (55 degrees C) temperatures, (b) those that rotate
      freely at room temperature, and (c) those that do not rotate at room temperature
      but do so at higher temperatures. One should note that rotation here refers to
      the NMR timescale and it is quite possible that all molecules may rotate at much
      longer timescales than the one probed here. A slight variation in structure
      alters the rotational mobility of the guest molecules.

PMID- 20055366
TI  - Modeling ion binding to humic substances: elastic polyelectrolyte network model.
AB  - A new model for the electrostatic contribution to ion binding to humic substances
      is proposed and applied to published data for proton binding to fulvic and humic
      acids. The elastic polyelectrolyte network model treats humic substance particles
      as composed by two parts, an external one directly in contact with the solution,
      and an internal part or gel fraction which is considered, from a statistical
      point of view, as a charged polymer network swelled by the electrolyte solution,
      in the framework of the Flory polymer network theory. The electrostatic effect is
      given by a Donnan-like potential, which can be regarded as an average value over
      the gel fraction of the humic particle. The gel fraction expands as the pH and
      humic charge are increased, determining the Donnan potential and consequently the
      ion activity inside the gel. The model was fitted to published experimental data
      with good agreement. The model predictions are discussed, and the behavior
      suggests, for some cases, the presence of a transition between closed and open
      structures attributed to the presence, at low pH, of intramolecular hydrogen
      bonds which are removed as the carboxylic sites become deprotonated.

PMID- 20055367
TI  - Hierarchically nanostructured barium sulfate fibers.
AB  - BaSO(4) nanostructures with controlled morphologies were successfully produced
      via one-step process through precipitation of BaSO(4) in aqueous and organic
      media. The synthesis is carried out by mixing solutions of BaCl(2) and Na(2)SO(4)
      in presence of EDTA (disodium ethylenediaminetetraacetic acid) at room
      temperature. The influence of the reaction conditions such as initial reactants
      concentration, pH, EDTA/[Ba(2+)] ratio and aging on the BaSO(4) nanoparticles
      organization is studied. Using EDTA in aqueous media, spherical secondary
      particles of 500 nm diameter are obtained, which are formed by 4 nm size primary
      particles. With dimethyl sulfoxide and small amounts of water (5%) and EDTA, the
      aging process allows the production of long homogeneous fibers, related to
      hierarchical organization of BaSO(4) nanoparticles. Direct observation of self
      assembling of primary particles by HRTEM allows proposing a mechanism for fiber
      formation, which is based on multipolar attractions that lead to a brick-by-brick
      organization along a preferential orientation. Results evidence the role of EDTA
      as controlling agent of the morphology and primary and secondary mean particle
      size.

PMID- 20055368
TI  - Spontaneous formation of densely stacked multilamellar vesicles in
      dioctadecyldimethylammonium bromide/oleosiloxane mixtures.
AB  - A double-tailed surfactant, for example, dioctadecyldimethylammonium bromide
      (DODAB), tends to form bilayer fragments rather than vesicles in aqueous solution
      upon sonication. This Letter reports on the morphological transformations of the
      membrane fragments leading to multilamellar vesicle formation. The surfactant
      membranes were swollen with tetra(11-methoxy-11
      oxoundecyl)tetramethylcyclotetrasiloxane (3) (a cyclosiloxane with covalently
      attached fatty-acid esters) up to 50 mol % based on the surfactant content. That
      compound was synthesized by hydrosilylation of 1,3,5,7
      tetramethylcyclotetrasiloxane with four molecules of methyl undec-10-enoate.
      Using cryo-transmission electron microscopy (cryo-TEM), it has been shown that
      densely stacked multilamellar vesicles form spontaneously in the sonicated DODAB
      dispersion containing 50 mol % of the compound 3 after adjusting pH to the value
      of 9.5. This occurs as a result of the hydrolysis of ester bonds of the compound
      3 inside the membrane with formation of tetra(11
      carboxyundecyl)tetramethylcyclotetrasiloxane (4). The carboxylic groups in
      compound 4 are ionized under experimental conditions. That results in the
      appearance of the negative charge at the surface which neutralizes the positively
      charged molecules of DODAB, thus reducing repulsive interactions between the
      membrane fragments. Additionally, as was shown using Langmuir monolayer
      measurements, the presence of compound 4 expands the DODAB film and decreases its
      bending rigidity. That makes the bending process considerably easier and promotes
      formation of multilamellar vesicles.

PMID- 20055369
TI  - Correlating interfacial tensions with surface tensions: a gibbsian approach.
AB  - The Gibbs approach to the definition of interfacial and surface tensions is used
      for developing a general form for a correlation between interfacial tensions and
      their corresponding surface tensions. This general equation can serve as a
      starting point for either further fundamental development or an empirical search
      for a correlation that fits experimental data. In this Article, the latter
      approach is followed. The general equation is transformed by a few reasonable
      assumptions into a relatively simple framework for empirically correlating
      interfacial tensions with their corresponding surface tensions. The agreement of
      results of the present empirical correlation with a large body of experimental
      data for interfacial tensions in saturated liquid-liquid systems is better than
      that of previously suggested correlations. It is hoped that this correlation will
      be useful also for solid-liquid interfacial tensions, for which direct
      measurements are not yet available.

PMID- 20055370
TI  - Atomic force microscopy characterization of cellulose nanocrystals.
AB  - Cellulose nanocrystals (CNCs) are gaining interest as a "green" nanomaterial with
      superior mechanical and chemical properties for high-performance nanocomposite
      materials; however, there is a lack of accurate material property
      characterization of individual CNCs. Here, a detailed study of the topography,
      elastic and adhesive properties of individual wood-derived CNCs is performed
      using atomic force microscopy (AFM). AFM experiments involving high-resolution
      dynamic mode imaging and jump-mode measurements were performed on individual CNCs
      under ambient conditions with 30% relative humidity (RH) and under a N(2)
      atmosphere with 0.1% RH. A procedure was also developed to calculate the CNC
      transverse elastic modulus (E(T)) by comparing the experimental force-distance
      curves measured on the CNCs with 3D finite element calculations of tip
      indentation on the CNC. The E(T) of an isolated CNC was estimated to be between
      18 and 50 GPa at 0.1% RH; however, the associated crystallographic orientation of
      the CNC could not be determined. CNC properties were reasonably uniform along the
      entire CNC length, despite variations along the axis of 3-8 nm in CNC height. The
      range of RH used in this study was found to have a minimal effect on the CNC
      geometry, confirming the resistance of the cellulose crystals to water
      penetration. CNC flexibility was also investigated by using the AFM tip as a
      nanomanipulator.

PMID- 20055371
TI  - Control of cell surface and functions by layer-by-layer nanofilms.
AB  - Various nanometer-sized multilayers were directly prepared onto the surface of
      mouse L929 fibroblast cells by a layer-by-layer (LbL) assembly technique to
      control the cell surface microenvironment and cell functions, such as viability,
      morphology, and proliferation. The species of LbL nanofilms strongly affected the
      cell morphology and growth. Polyelectrolyte (PE) multilayers induced a round
      shaped morphology of the adhered cells, although each component of the
      multilayers had high cytocompatibility, whereas fibronectin (FN)-gelatin (G) and 
      dextran sulfate (DS) multilayers with FN-binding domain interactions (FN films)
      showed extended morphologies of the cells similar to that of control cells
      (without films). A clear difference in cell proliferation was observed for PE and
      FN films. The cells with FN films on their surfaces showed good proliferation
      profiles independent of the film thickness, but cell proliferation was not
      observed using the PE films although the cells survived during the culture
      period. Fluorescence microscopic and scanning electron microscopic observations
      clearly suggested a nanometer-sized meshwork morphology of the FN films on the
      cell surface after 24 h of incubation, whereas the PE films showed homogeneous
      film morphologies on the cell surface. These nanomeshwork morphologies seemed to
      be similar to the fibrous structure of the natural extracellular matrix. The
      results of this study demonstrated that the components, charge, and morphology of
      LbL nanofilms prepared directly on the cell surface strongly affected cell
      functions, and the effects of these LbL nanofilms on cell functions differed
      vastly as compared to PE films prepared on a substrate. The preparation of LbL
      nanofilms onto a cell surface might be a novel and interesting technique to
      control cell functions.

PMID- 20055372
TI  - meso-Substituted bisanthenes as soluble and stable near-infrared dyes.
AB  - Three meso-substituted bisanthenes, 4-6, were prepared in a short synthetic route
      from the bisanthenequinone. They exhibit largely improved stability and
      solubility in comparison to the parent bisanthene. All of these compounds also
      show near-infrared (NIR) absorption and emission with high to moderate
      fluorescence quantum yields. Amphoteric redox behavior was observed for 4-6 by
      cyclic voltammetry, and these compounds can be reversibly oxidized and reduced
      into respective cationic and anionic species by both electrochemical and chemical
      processes. In addition, compound 5 adopts a herringbone pi-stacking motif in the
      single crystal.

PMID- 20055373
TI  - Benzodifurantrione: a stable phenylogous enol.
AB  - The first example of a stable phenylogous enol, resulting from an extended keto
      enol tautomerization across a benzene ring, is described. The enol has been
      isolated, and its structure was proven by X-ray crystallography. The equilibrium
      between the keto- and enol-tautomers has been extensively studied and quantified
      in solution by NMR and UV-vis spectroscopy. The position of equilibrium showed a
      linear correlation to the Kamlet-Taft solvatochromic scale for solvent H-bond
      acceptor strength (beta(OmicronEta)), and the equilibrium was proven to be fully
      dynamic, obeying first-order equilibrium kinetics. To attempt to explain why
      enolization occurs, at what surprisingly appears to be the expense of aromatic
      resonance stabilization, various structural features have been considered and
      explored further with the aid of MO calculations. Nucleus independent chemical
      shift (NICS) index of aromaticity calculations for each of the rings comprising
      both tautomers showed that while the central benzene ring loses aromaticity on
      enolization, the alpha-keto-lactone ring showed an unexpected and significant
      antiaromaticity in the keto-tautomer, which is by no means intuitive. The loss of
      stabilization energy associated with the central benzene ring is, therefore, to a
      certain degree compensated by removal of the antiaromatic destabilization of the
      alpha-keto-lactone ring rendering the two structures much closer in energy than
      would otherwise be expected.

PMID- 20055374
TI  - Aldehyde- and ketone-induced tandem decarboxylation-coupling (Csp(3)-Csp) of
      natural alpha-amino acids and alkynes.
AB  - An interesting aldehyde- and ketone-induced intermolecular tandem decarboxylation
      coupling (Csp(3)-Csp) catalyzed by copper with use of natural alpha-amino acids
      as starting materials is developed under neutral conditions with the production
      of CO(2) and H(2)O as the only byproducts. Various functionalized nitrogen
      containing compounds were obtained by this method. In these processes,
      interesting regioselectivites of the alkylation were observed, which has been
      rationalized by the relative stability of proposed resonance structures based on
      computation methods.

PMID- 20055375
TI  - An enantioselective synthetic route toward second-generation light-driven rotary
      molecular motors.
AB  - Controlling the unidirectional rotary process of second-generation molecular
      motors demands access to these motors in their enantiomerically pure form. In
      this paper, we describe an enantioselective route to three new second-generation
      light-driven molecular motors. Their synthesis starts with the preparation of an
      optically active alpha-methoxy-substituted upper-half ketone involving an
      enzymatic resolution. The subsequent conversion of this ketone to the
      corresponding hydrazone by treatment with hydrazine led to full racemization.
      However, conversion to a TBDMS-protected hydrazone by treatment with bis-TBDMS
      hydrazine, prepared according to a new procedure, proceeds with nearly full
      retention of the stereochemical integrity. Oxidation of the TBDMS-protected
      hydrazone and subsequent coupling to a lower-half thioketone followed by
      recrystallization provided the molecular motors with >99% ee. As these are the
      first molecular motors that have a methoxy substituent at the stereogenic center,
      the photochemical and thermal isomerization steps involved in the rotary cycle of
      one of these new molecules were studied in detail with various spectroscopic
      techniques.

PMID- 20055376
TI  - Synthetic approach to polysubstituted furans: an efficient addition/oxidative
      cyclization of alkynoates and 1,3-dicarbonyl compounds.
AB  - A novel and reliable method for the direct construction of polysubstituted furans
      is reported. The key transformation involves Sn(II)- and Cu(I)-involved
      addition/oxidative cyclization of alkynoates and 1,3-dicarbonyl compounds in the
      presence of 2,3-dichloro-5,6-dicyanobenzoquinone.

PMID- 20055377
TI  - Instantaneous liquid interfaces.
AB  - We describe and illustrate a simple procedure for identifying a liquid interface
      from atomic coordinates. In particular, a coarse-grained density field is
      constructed, and the interface is defined as a constant density surface for this
      coarse-grained field. In applications to a molecular dynamics simulation of
      liquid water, it is shown that this procedure provides instructive and useful
      pictures of liquid-vapor interfaces and of liquid-protein interfaces.

PMID- 20055378
TI  - Assessing the stability of Alzheimer's amyloid protofibrils using molecular
      dynamics.
AB  - Amyloid fibrils represent a stable form of many misfolded proteins associated
      with numerous diseases. Among these are Parkinson's disease (alpha-synuclein),
      Type II diabetes (islet amyloid polypeptide), and Alzheimer's disease (amyloid
      beta-peptide, Abeta). The appearance of Abeta fibrils in neural tissue is a
      hallmark of Alzheimer's disease, and many studies have been conducted to
      determine and analyze the structure of these protein aggregates. The principal
      toxic species in Alzheimer's disease are believed to be soluble, oligomeric
      aggregates of Abeta, but numerous studies have found that the insoluble
      fibrillated form of the peptide also contributes to neurotoxicity. Thus, to
      design therapeutic agents to combat the progression of Alzheimer's disease, it is
      worthwhile to understand the thermodynamics of destabilizing these aggregates and
      the features that contribute to their stability. In this work, we present a
      systematic study of several factors that influence the stability of Abeta(42)
      fibrils following in silico mutation. We have employed standard molecular
      dynamics, as well as center-of-mass pulling and umbrella sampling, to study the
      thermodynamics of peptide dissociation from the core of a model protofibril at
      physiological temperature. Results indicate that a finite level of hydration
      around the Asp23-Lys28 salt bridge is crucial to protofibril stability, while
      mutation of Phe19 to glycine has no effect on the binding free energy of the
      terminal peptide. Packing between Ile32 and the aliphatic portion of the Lys28
      side chain serves to regulate the level of hydration in the core of the
      protofibril and thus rigidify the Asp23-Lys28 salt bridge. These observations are
      important for designing compounds that target Abeta aggregates; interrupting
      these native interactions may destabilize these assemblies and ameliorate their
      toxicity.

PMID- 20055379
TI  - Aqueous dispersion of conjugated polymers by colloidal clays and their film
      photoluminescence.
AB  - The plate-shaped clays enabled us to disperse water-insoluble conjugated polymers
      (CPs) into a colloidal form and an aqueous process for making CP films. Simple
      pulverization of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH
      PPV) with silicate clays rendered the powder mixture an unusual dispersing
      behavior in water. The most effective clay was selected from screening several
      natural and synthetic clays including synthetic fluorinated mica (Mica), sodium
      montmorillonite (MMT), synthetic smectite (SWN), and cationic layered double
      hydroxide (LDH). A high aspect ratio and intensive charge density (2.1 e nm(-1))
      of Mica were highly effective for promoting the CP dispersion. The enhancement
      for dispersing MEH-PPV is rated in the following trend: Mica > MMT > SWN > LDH.
      The result is rationalized by the influences of their geometric shape and ionic
      charge of clay on MEH-PPV in water. Two other representative CPs, sulfonated
      polyaniline (SPA) and triphenyl phosphine oxide cored polyaniline (TPOPA), were
      used to generalize the CP/clay colloidal behavior. All of the three CPs as in an
      aqueous form can be coated into hybrid films. Under an ultraviolet lamp, these
      films showed color emissions, orange for MEH-PPV/Mica, olive for SPA/Mica, and
      green for TPOPA/Mica, which are consistent with the photoluminescence
      measurements.

PMID- 20055380
TI  - Induction of amyloid fibrils by the C-terminal fragments of TDP-43 in amyotrophic
      lateral sclerosis.
AB  - TAR DNA-binding protein 43 (TDP-43) has been identified as the major
      ubiquitinated aggregates in the inclusion bodies in the patients of amyotrophic
      lateral sclerosis (ALS) since 2006 and become a crucial culprit for ALS and
      related motor neuron diseases. Recent literature has further indicated that the
      major components of these aggregates are hyper-phosphorylated TDP-43 C-terminus.
      In an effort to clarify the conformational and physical properties of its
      disordered C-terminal domain, we have synthesized several peptide fragments and
      shown that only D1 within D1-4 can form twisted fibrils with a cross section of
      approximately 11 nm in width under the incubation of phosphate buffer. In
      contrast, the D2-4 peptides all formed amorphous aggregates, showing different
      aggregation propensities. In addition to D1, two pathological mutant peptides,
      A315T and G294A, can also form fibrils that share similar shape and morphology
      with neuronal cytoplasmic inclusions. We propose that the residues with this
      region (287-322), which contains myriads of glycine repeats, may contribute
      significantly to the fiber formation as well as aggregation propensity. Moreover,
      from the conformational characterizations of D1, A315T, and G294A with EM, CD,
      fluorescence, and Raman spectroscopy, we found that all three peptides formed an
      amyloid structure, providing insights into the nature of its aggregation vis a
      vis the other fragments in the C-terminus of TDP-43.

PMID- 20055381
TI  - Electrophoresis of a charge-regulated soft sphere in a charged cylindrical pore.
AB  - The boundary effect on the electrophoresis of a soft spherical particle, which
      comprises a rigid core and a porous layer, along the axis of a cylindrical pore
      is analyzed under the conditions of low surface potential and weak applied
      electric field. The porous layer of the particle is of charge-regulated nature
      where the distribution of fixed charge depends on the degree of
      dissociation/association reaction of the ionizable function groups contained in
      the porous layer. The pore might be charged, implying that the effect of
      electroosmotic flow can play a role. The influences of the nature of the porous
      layer of a particle, the thickness of the double layer, the pH of the bulk
      liquid, and the relative size of a pore on the electrophoretic behavior of the
      particle are investigated. Several unexpected and interesting results are
      obtained. For instance, if the pH value of the bulk liquid or the thickness of
      the membrane layer takes a medium large value, the electrophoretic mobility of
      the particle has a local maximum as the thickness of the double layer varies.

PMID- 20055382
TI  - Mechanically stiffened and thermally softened Raman modes of ZnO crystal.
AB  - An analytical form connecting the energy shift of Raman modes directly to the
      bonding identities (order, nature, length, energy) of a specimen and the response
      of the bonding identities to the applied stimuli of temperature and pressure was
      presented for a deeper understanding of the atomistic origin of the ZnO Raman
      shift. Theoretical reproduction based on the BOLS correlation theory [Sun, C. Q.
      Prog. Solid State Chem. 2007, 35, 1] and the local bond average (LBA) approach
      [Sun, C. Q. Prog. Mater. Sci. 2009, 54, 179] of the measurements revealed that
      the thermally softened ZnO Raman modes arise from bond expansion and bond
      weakening due to vibration and that the pressure-stiffened Raman modes result
      from bond compression and bond strengthening due to mechanical work hardening.
      The developed approach could be useful in generalizing the lattice dynamics
      directly to the process of vibration and relaxation of a representative bond of
      the specimen under external stimuli.

PMID- 20055384
TI  - Evidence of double-walled Al-Ge imogolite-like nanotubes. a cryo-TEM and SAXS
      investigation.
AB  - It has been recently discovered that the synthesis of Al-Ge imogolite-like
      nanotubes is possible at high concentration. Despite this initial success, the
      structure of these Al-Ge imogolite-like nanotubes remains not completely
      understood. Using high resolution cryo-TEM and Small Angle X-ray Scattering, we
      unravel their mesoscale structure in two contrasted situations. On the one hand,
      Al-Ge imogolite nanotubes synthesized at 0.25 M are double-walled nanotubes of
      4.0 +/- 0.1 nm with an inner tube of 2.4 +/- 0.1 nm. Moreover, SAXS data also
      suggest that the two concentric tubes have an equal length and identical wall
      structure. On the other hand, at higher concentration (0.5M), both SAXS and cryo
      TEM data confirm the formation of single-walled nanotubes of 3.5 +/- 0.15 nm.
      Infrared spectroscopy confirms the imogolite structure of the tubes. This is the
      first evidence of any double-walled imogolite or imogolite-like nanotubes likely
      to renew interest in these materials and associated potential applications.

PMID- 20055383
TI  - Ultrafast optical excitations in supramolecular metallacycles with charge
      transfer properties.
AB  - New organometallic materials such as two-dimensional metallacycles and three
      dimensional metallacages are important for the development of novel optical,
      electronic, and energy related applications. In this article, the ultrafast
      dynamics of two different platinum-containing metallacycles have been
      investigated by femtosecond fluorescence upconversion and transient absorption.
      These measurements were carried out in an effort to probe the charge transfer
      dynamics and the rate of intersystem crossing in metallacycles of different
      geometries and dimensions. The processes of ultrafast intersystem crossing and
      charge transfer vary between the two different classes of metallacyclic systems
      studied. For rectangular anthracene-containing metallacycles, the electronic
      coupling between adjacent ligands was relatively weak, whereas for the triangular
      phenanthrene-containing structures, there was a clear interaction between the
      conjugated ligand and the metal complex center. The transient lifetimes increased
      with increasing conjugation in that case. The results show that differences in
      the dimensionality and structure of metallacycles result in different optical
      properties, which may be utilized in the design of nonlinear optical materials
      and potential new, longer-lived excited state materials for further electronic
      applications.

PMID- 20055385
TI  - Chemically programmed ultrahigh density two-dimensional semiconductor
      superlattice array.
AB  - Designing an ultrahigh density linear superlattice array consisting of periodic
      blocks of different semiconductors in the strong confinement regime via a direct
      synthetic route remains an unachieved challenge in nanotechnology. We report a
      general synthesis route for the formulation of a large-area ultrahigh density
      superlattice array that involves adjoining multiple units of ZnS rods by prolate
      CdS particles at the tips. A single one-dimensional wire is 300-500 nm long and
      consists of periodic quantum wells with a barrier width of 5 nm provided by ZnS
      and a well width of 1-2 nm provided by CdS, defining a superlattice structure.
      The synthesis route allows for tailoring of ultranarrow laserlike emissions (fwhm
      approximately 125 meV) originating from strong interwell energy dispersion along
      with control of the width, pitch, and registry of the superlattice assembly. Such
      an exceptional high-density superlattice array could form the basis of ultrahigh
      density memories in addition to offering opportunities for technological
      advancement in conventional heterojunction-based device applications.

PMID- 20055386
TI  - Catalytic asymmetric synthesis of 3-aminooxindoles: enantiofacial selectivity
      switch in bimetallic vs monometallic Schiff base catalysis.
AB  - A highly enantioselective catalytic asymmetric access to 3-aminooxindoles with a
      tetrasubstituted carbon stereocenter is described. 1-2 mol % of homobimetallic
      (R)-Ni(2)-Schiff base 1 catalyzed the asymmetric amination of 3-substituted
      oxindoles with azodicarboxylates to give (R)-products in 99-89% yield and 99-87%
      ee. Reversal of enantiofacial selectivity was observed between bimetallic and
      monometallic Schiff base complexes, and monometallic (R)-Ni-Schiff base 2c gave
      (S)-products in 98-80% ee. Transformation of the products into an optically
      active oxindole with a spiro-beta-lactam unit and a known key intermediate for AG
      041R synthesis is also described.

PMID- 20055387
TI  - Evidence of water adsorption in hydrophobic nanospaces of highly pure double
      walled carbon nanotubes.
AB  - Highly pure double-walled carbon nanotubes synthesized by a catalytic chemical
      vapor deposition method have a quasi one-dimensional nanopore system. We
      determined these nanotubes' nanopore structures by means of molecular probe
      adsorption using N(2) at 77 K, CO(2) at 273 K, and water at 298, 308, and 318 K,
      as well as high-resolution transmission electron microscopy. The water vapor
      adsorption behavior of this system was quite unusual. At a lower relative
      pressure of P/P(0) = 0.3-0.65, water filled the interstitial nanopores, and at
      relative pressures higher than this range, water also filled the interbundle
      nanopores. This study is the first to our knowledge that has provided direct
      evidence of water adsorption in hydrophobic nanospaces of highly pure double
      walled carbon nanotubes.

PMID- 20055388
TI  - Design, synthesis, and characterization of a persistent nonacene derivative.
AB  - A significant technical barrier (i.e., facile oxidative degradation) that has
      prevented the preparation of large acenes has now been breached. Using a
      combination of experimentally and theoretically derived substituent effects, the
      design, synthesis, isolation, and characterization of the first persistent
      nonacene derivative is described. The molecular design strategy includes
      placement of arylthio (or alkylthio) substituents on the terminal rings of the
      nonacene skeleton, effectively converting an open-shell singlet diradical into a
      closed-shell system. These powerful substituent effects appear to be suitable for
      the synthesis of other persistent, soluble, large acene derivatives required for
      advanced thin-film organic semiconductor applications.

PMID- 20055389
TI  - Slow magnetic relaxation in a high-spin iron(II) complex.
AB  - Slow magnetic relaxation is observed for [(tpa(Mes))Fe](-), a trigonal pyramidal
      complex of high-spin iron(II), providing the first example of a mononuclear
      transition metal complex that behaves as a single-molecule magnet. Dc magnetic
      susceptibility and magnetization measurements reveal a strong uniaxial magnetic
      anisotropy (D = -39.6 cm(-1)) acting on the S = 2 ground state of the molecule.
      Ac magnetic susceptibility measurements indicate the absence of slow relaxation
      under zero applied dc field as a result of quantum tunneling of the
      magnetization. Application of a 1500 Oe dc field initiates slow magnetic
      relaxation, which follows a thermally activated tunneling mechanism at high
      temperature to give an effective spin-reversal barrier of U(eff) = 42 cm(-1) and
      follows a temperature-independent tunneling mechanism at low temperature. In
      addition, the magnetic relaxation time shows a pronounced dc-field dependence,
      with a maximum occurring at approximately 1500 Oe.

PMID- 20055390
TI  - Anguinomycins and derivatives: total syntheses, modeling, and biological
      evaluation of the inhibition of nucleocytoplasmic transport.
AB  - The preparation of the polyketide natural products anguinomycin C and D is
      reported based on key steps such as Negishi stereoinversion cross coupling,
      Jacobsen Cr(III)-catalyzed Hetero Diels-Alder reaction, Evans B-mediated syn
      aldol chemistry, and B-alkyl Suzuki-Miyaura cross coupling. The configuration of
      both natural products was established as (5R,10R,16R,18S,19R,20S). Biological
      evaluation demonstrated that these natural products are inhibitors of the nuclear
      export receptor CRM1, leading to shutdown of CRM1-mediated nuclear protein export
      at concentrations above 10 nM. Analogues of anguinomycin and leptomycin B (LMB)
      have been prepared, and the simple alpha,beta-unsaturated lactone analogue 4 with
      a truncated polyketide chain retains most of the biological activity (inhibition
      above 25 nM). The structural basis for this inhibition has been demonstrated by
      modeling the transport inhibitors into X-ray crystal structures, thus
      highlighting key points for successful and strong biological action of
      anguinomycin and LMB.

PMID- 20055391
TI  - Carboxylate as the protonation site in (Peroxo)diiron(III) model complexes of
      soluble methane monooxygenase and related diiron proteins.
AB  - Addition of H(+) to a synthetic (mu-1,2-peroxo)diiron(III) model complex results
      in protonation of a carboxylate rather than the peroxo ligand. This conclusion is
      based on spectroscopic evidence from UV-vis, (57)Fe Mossbauer, resonance Raman,
      infrared, and (1)H/(19)F NMR studies. These results suggest a similar role for
      protons in the dioxygen activation reactions in soluble methane monooxygenase and
      related carboxylate-bridged diiron enzymes.

PMID- 20055392
TI  - Total synthesis of (-)-mersicarpine.
AB  - The total synthesis of (-)-mersicarpine was achieved in 10 steps from a known
      ketoester. Our synthesis features an Eschenmoser-Tanabe-type fragmentation to
      synthesize an alkyne unit containing a quaternary carbon center, a facile
      construction of the indole skeleton via a combination of a Sonogashira coupling
      and a gold(III) catalyzed cyclization, as well as a one-pot process to arrange
      the cyclic imine and the hemiaminal moieties. Our synthesis unambiguously
      confirmed the reported structure of (-)-mersicarpine including the absolute
      configuration.

PMID- 20055393
TI  - NHC catalyzed oxidations of aldehydes to esters: chemoselective acylation of
      alcohols in presence of amines.
AB  - Not just one but two carbenes of the same structure act cooperatively in
      oxidative acylations of alcohols with aldehydes by using a readily available
      cheap organic oxidant. Alcohols are selectively acylated in the presence of
      amines by cooperative carbene catalysis. Quantum chemical calculations support
      the suggested mechanism.

PMID- 20055394
TI  - Zooming into pi-stacked manifolds of nucleobases: ionized states of dimethylated
      uracil dimers.
AB  - The electronic structure of 1,3-dimethyluracil and its dimer is characterized by
      ab initio calculations. The methylation eliminates the H-bonded isomers and
      allows one to focus on the pi-stacked manifold. In the neutral species,
      methylation increases the binding energy by 3-4 kcal/mol and reduces the lowest
      ionization energy (IE) by 0.6 eV. Other valence IEs are also red-shifted and the
      relative state ordering is the same as in uracil; however, the magnitude of the
      effect varies from 0.37 to 0.86 eV. The largest shifts are observed for the
      states with large contributions from lone pairs of nitrogens, which are primary
      substitution sites. The effect of stacking interactions on IEs is similar in
      methylated and non-methylated dimers: the lowest IE is red-shifted by 0.37 and
      0.35 eV relative to the respective monomers. The splittings between other pairs
      of dimer states derived from the in-phase and out-of-phase combinations of the
      monomers' states are also similar to non-methylated uracil dimers, except for the
      states that include a large weight of nitrogen lone pairs. Because of the
      nonuniform effect on both monomers' levels and the shifts, the relative order of
      the ionized states in the dimer changes, relative to that of the non-methylated
      uracil dimer. The ionized stacked isomers show two different relaxation patterns-
      several isomers form structures with the delocalized hole stabilized by the
      orbital overlap, whereas others relax to the structures with the localized hole
      stabilized by electrostatic interactions. Electronic spectra of the ionized
      species at the neutral and cation geometries are presented and discussed.

PMID- 20055395
TI  - Radii of atomic ions determined from diatomic ion-He bond lengths.
AB  - We propose a new definition of the effective radius of an atomic ion: the bond
      distance (R(e)) of the ion/He diatomic complex minus the van der Waals radius of
      the helium atom. Our rationale is that He is the most chemically inert and least
      polarizable atom, so that its interaction with the outer portions of the electron
      cloud causes the smallest perturbation of it. We show that such radii, which we
      denote R(XHe), make good qualitative sense. We also compare our R(XHe) values to
      more traditional ionic radii from solid crystal X-ray measurements, as well as
      estimates of such radii from "ionic" gas-phase MF, MOM, MF(+), and MO molecules,
      where M is a metal atom. Such comparisons lead to interesting conclusions about
      bonding in ionic crystals and in simple gas-phase oxide and fluoride molecules.
      The definition is shown to be reasonable for -1, +1, and even for many of the
      larger +2 atomic ions. Another advantage of the R(XHe) definition is that it is
      also consistently valid for ground states and excited states of both neutral
      atoms and atomic ions, even for open-shell np and nd cases where the electron
      clouds of the ions are not spherically symmetric and R(XHe) thus depends on the
      "approach" direction of the He atom. Finally, we note that when there is a
      contribution from covalent bonding with the He atom, and/or in cases where the
      ion is small and has a very high charge, so that there is distortion even of the
      He 1s electrons, R(XHe) is not expected to be representative of the size of the
      ion. We then suggest that in these cases small, and sometimes unphysical, values
      of R(XHe) are diagnostic of the fact that simple "physical" interactions have
      been supplemented by a "chemical" component.

PMID- 20055396
TI  - Electron attachment to formamide clusters in helium nanodroplets.
AB  - Electron attachment to formamide clusters in helium nanodroplets is reported for
      the first time. In contrast to the gas phase, parent anions are seen following
      low energy electron attachment to both the monomer and the small clusters. This
      is attributed to formation of dipole (or quadrupole) bound anions. In addition to
      the bare anions, the mass spectra also show the monomer and clusters with
      attached helium atoms. The affinity for attaching helium atoms strongly varies
      with cluster size; for example, the dimer anion is more than 10 times more likely
      to bind one or more helium atoms than the monomer. Possible binding sites for the
      helium atoms are discussed.

PMID- 20055397
TI  - Excited states of [3.3](4,4')biphenylophane: the role of charge-transfer
      excitations in dimers with pi-pi interaction.
AB  - The singlet and triplet electronic excitation manifold of
      [3.3](4,4')biphenylophane (BPP), an intramolecular dimer, and 4,4'
      dimethylbiphenyl (DMBP), the corresponding monomer, has been analyzed by
      employing the approximate coupled-cluster singles and doubles model (CC2). The
      calculated triplet-triplet and singlet-singlet transient absorption spectra show
      good agreement with recent experimental results. The calculations suggest a
      strong interaction of the two biphenyl moieties of BPP in the first singlet and
      triplet excited states due to the overlapping pi-electron systems, and Forster
      Dexter theory for weak coupling cannot be applied. Both the first excited singlet
      and triplet states of BPP can be characterized as excimeric states with a strong
      admixture of charge-transfer contributions.

PMID- 20055398
TI  - Near degeneracy effects on the low-lying spectrum of the iron atom.
AB  - The ground state and the LS terms coming from the ground-state configuration,
      [Ar]-3d(6)4s(2), of the iron atom are studied by carrying out an all electron
      Variational Monte Carlo calculation. Explicitly correlated trial functions
      including near degeneracy effects are used. The effect of electronic correlations
      and the importance of near degeneracy effects are systematically analyzed for the
      states here considered and compared with the experimental values. Correlations
      are important to reproduce, even qualitatively, the low-lying spectrum of this
      atom. A significant quantitative improvement when comparing with the experimental
      values is achieved when near degeneracy is considered along with dynamic
      correlations in the variational trial wave function. Finally, the effect of
      relativity on the results here reported is discussed.

PMID- 20055399
TI  - Reactions of iron atoms with benzene.
AB  - The reaction of iron atoms with benzene has been studied for nearly 40 years.
      Despite this, there is no agreement as to the nature of the products. With the
      aid of density functional theory calculations of the energetics and the infrared
      spectra of the various species, the present work provides a rationalization of
      the conflicting reports regarding the nature of the products of the reaction of
      iron atoms with benzene in low-temperature matrices. At low temperature in dilute
      benzene matrices, Fe(eta(6)-C(6)H(6)) and Fe(eta(6)-C(6)H(6))(2) are the major
      products. At high iron concentrations, Fe(2)(eta(2)-C(6)H(6)) is also formed. In
      pure benzene at low temperature, Fe(eta(6)-C(6)H(6))(2) and Fe(eta(6)
      C(6)H(6))(eta(4)-C(6)H(6)) are formed. None of the species undergo
      photoexcitation to give insertion products HFe(C(6)H(5)). In pure benzene at 77
      K, Fe(eta(6)-C(6)H(6))(eta(4)-C(6)H(6)) is the major product, together with small
      amounts of Fe(eta(6)-C(6)H(6))(2) and iron clusters. The infrared spectra of pure
      benzene are complicated by the activation of infrared forbidden modes by the
      presence of the metal atom.

PMID- 20055400
TI  - D2Pi(u), C2Pi(u) <-- X2Pi(g) electronic transitions of NCCN+.
AB  - The electronic absorption spectrum of NCCN(+) in the gas phase was measured at
      approximately 15 K in a 22-pole ion trap. The spectra show two band systems
      assigned to the C(2)Pi(u)-X(2)Pi(g) and D(2)Pi(u)-X(2)Pi(g) transitions with
      origin band maxima at 17,363 (3) and 33,409 (5) cm(-1), respectively. Both
      absorptions show distinct vibrational structure with progressions in nu(2) as
      well as combinations of double quanta excitations in nu(4) and nu(5). Rotational
      structure of the 0(0)(0) bands could not be resolved, which indicates that the
      C(2)Pi(u) and D(2)Pi(u) states have a lifetime on the order of a hundred
      femtoseconds because of fast intramolecular processes.

PMID- 20055401
TI  - Nitrogen isotopic records of terrestrial pollution encoded in Floridian and
      Bahamian gorgonian corals.
AB  - Stable nitrogen isotope (delta(15)N) analysis has proven an effective
      "fingerprint" of sewage contamination in coral reef environments; however, short
      term variability in nitrogen cycling and isotopic fractionation may obscure long
      term trends. Here, we examine delta(15)N signatures in the organic endoskeletons
      of long-lived (20-40 years) gorgonian corals. Specimens were collected from
      relatively pristine reefs off Green Turtle Cay, Bahamas, and from reefs off
      southeast Florida heavily impacted by multiple sources of anthropogenic nitrogen.
      The delta(15)N of the most recently grown skeleton (branch tips) ranged from +2
      to +3 per thousand at Green Turtle Cay, and +4.5 to +10 per thousand off Florida.
      These values closely match the delta(15)N of macroalgae collected from the same
      locations, indicating that gorgonian corals are isotopically similar to primary
      producers, and therefore suitable for assessing sources of dissolved inorganic
      nitrogen. Differences in the delta(15)N between younger and older skeleton
      indicated an overall decline of -0.34 +/- 0.06 per thousand (1 s.e) over the last
      20 - 40 years at Green Turtle Cay, reflecting a possible increase in nitrogen
      fixation and/or atmospheric deposition of anthropogenic nitrogen. Off southeast
      Florida, there was an overall increase in delta(15)N over the same time period,
      reflecting increasing wastewater discharges from the rapidly growing population.
      These results highlight the usefulness of delta(15)N recorded in gorgonians and
      other long-lived organisms in assessing spatiotemporal patterns of nitrogen
      sources to coastal marine environments.

PMID- 20055402
TI  - Impact of low- and high-oxidation diesel particulate filters on genotoxic exhaust
      constituents.
AB  - Diesel exhaust contains several genotoxic compounds that may or may not penetrate
      diesel particulate filters (DPFs). Furthermore, the DPF-supported combustion of
      soot and adsorbed compounds may lead to the formation of additional pollutants.
      Herein, we compare the impact of 14 different DPFs on emissions of known
      genotoxic compounds. During a four year period, these DPFs were tested on a heavy
      duty diesel engine, operated in the ISO 8178/4 C1 cycle. Integral samples,
      including gas-phase and particle-bound matter were taken. All DPFs were efficient
      wall-flow filters with solid particulate number filtration efficiencies eta >
      98%. On the basis of their CO, NO, and NO(2) emission characteristics, two
      different filter families were distinguished. DPFs with high oxidation potential
      (hox, n = 8) converted CO and NO besides hydrocarbons, whereas low oxidation
      potential DPFs (lox, n = 6) did not support CO and NO oxidation but still
      converted hydrocarbons. Lox-DPFs reduced NO(2) from 1.0 +/- 0.3 (engine-out) to
      0.42 +/- 0.11 g/kWh (eta = 0.59), whereas hox-DPFs induced a NO(2) formation up
      to 3.3 +/- 0.7 g/kWh (eta = -2.16). Emissions of genotoxic PAHs decreased for
      both filter families. Conversion efficiencies varied for individual PAHs and were
      lower for lox- (eta = 0.31-0.87) than for hox-DPFs (eta = 0.75-0.98). Certain
      nitro-PAHs were formed indicating that nitration is an important step along PAH
      oxidation. For example, 1-nitronaphthalene emissions increased from 11 to 17 to
      21 microg/L without, with lox-, and hox-DPFs respectively, whereas 2
      nitronaphthalene emissions decreased from 25 to 19 to 4.7 microg/L. In contrast
      to our expectations, the nitration potential of lox-DPFs was higher than the one
      of hox-DPFs, despite the intense NO(2) formation of the latter. The filters
      converted most genotoxic PAHs and nitro-PAHs and most soot particles, acting as
      carriers for these compounds. Hox-DPF exhaust remains oxidizing and therefore is
      expected to support atmospheric oxidation reactions, whereas lox-DPF exhaust is
      reducing and consuming oxidants such as ozone, when mixed with ambient air.

PMID- 20055403
TI  - Dehydroindigo, the forgotten indigo and its contribution to the color of Maya
      Blue.
AB  - A comprehensive investigation of the electronic spectral and photophysical
      properties of the oxidized form of indigo, dehydroindigo (DHI), has been carried
      out in solution at 293 K. It is shown that dehydroindigo readily converts into
      its neutral keto form, the blue indigo, in a process which depends on the solvent
      and water content of the medium. DHI was investigated in toluene, in benzene, and
      in methanol and it was found that both the oxidized and the keto indigo forms are
      present in solution. In marked contrast to what has been found for keto-indigo,
      where the internal conversion channel dominates >99% of the excited state
      deactivation, or with the fully reduced leuco-indigo, where fluorescence,
      internal conversion, and singlet-to-triplet intersystem crossing coexist, in the
      case of DHI in toluene and benzene, the dominant excited state deactivation
      channel involves the triplet state. Triplet state yields (phi(T)) of 70-80%, with
      negligible fluorescence (< or = 0.01%) are observed in these solvents. In
      methanol the phi(T) value decreases to approximately 15%, with an increase of the
      fluorescence quantum yield to 2%, which makes these processes competitive with
      the S(1) --> S(0) internal conversion deactivation process. The data are
      experimentally compatible with the existence of a lowest lying singlet excited
      state of n,pi* origin in toluene and of pi,pi* origin in methanol. A time
      resolved investigation in the picosecond time domain suggests that the emission
      of DHI involves three interconnected species (involving rotational isomerism),
      with relative contributions depending on the emission wavelength. DFT
      calculations (B3LYP 6-31G** level) were performed in order to characterize the
      electronic ground (S(0)) and excited singlet (S(1)) and triplet (T(1)) states of
      DHI. The HOMO-LUMO transition was found to accompany an n --> pi* transition of
      the oxygen nonbonding orbitals to the central CC and adjacent C-N bonds.
      Calculations also revealed that in S(0) the two indole-like moieties deviate from
      planarity from ca. 20 degrees, whereas in S(1) and T(1) the predicted structure
      is basically planar; a gradual decrease of the carbon-carbon central bond
      distance is seen in the order S(0), S(1), T(1). An additional study on the blue
      pigment Maya Blue was made, and the comparison between the solid-state spectra of
      indigo, DHI, and Maya Blue suggests that, in line with recent investigations, DHI
      is present together with indigo in Maya Blue. These results are relevant to the
      discussion of the involvement of dehydroindigo in the palette of colors of the
      ancient Maya Blue pigment.

PMID- 20055404
TI  - 13C chemical shift tensors in hypoxanthine and 6-mercaptopurine: effects of
      substitution, tautomerism, and intermolecular interactions.
AB  - Principal values of the (13)C chemical shift tensor (CST) are measured for two
      biologically interesting and structurally related compounds, hypoxanthine and 6
      mercaptopurine, and differences in the values are discussed with an attempt to
      reveal chemical shifts sensitive to substitution and prototropic tautomerism in
      the purine ring. Furthermore, methods of density-functional theory (DFT) are used
      to calculate principal values of the (13)C chemical shift tensor and orientations
      of the principal components. Values calculated for isolated molecules are
      compared to those for several supramolecular clusters and then to experimental
      data to investigate the degree of modulation of the (13)C CSTs by molecular
      packing. Focusing on the protonated carbons, C2 and C8, which are crucial for
      relaxation measurements, we show that neglecting intermolecular interactions can
      lead to errors as large as 30 ppm in the delta(22) principal component. This has
      significant implications for the studies of molecular dynamics, employing spin
      relaxation, in large fragments of nucleic acids at high magnetic fields.

PMID- 20055405
TI  - Cyclic beta-helical/beta-hairpin D,L-alpha-peptide: study of its folding
      properties and structure refinement using molecular dynamics.
AB  - A molecular dynamics (MD) simulation study of a cyclic 22 residue D,L-alpha
      peptide is reported. The 154 experimental ROE distance bounds that determine a
      beta-helical fold in chloroform are all satisfied in MD simulations starting from
      the folded and from a refolded structure. Interestingly, the latter simulations
      generated structures of lower energy than the NMR model structures, thereby
      yielding a better conformational representation of the measured experimental
      data. The stability of the beta-helical fold, characterized by 16 beta-sheet
      hydrogen bonds, was investigated by varying the temperature and the solvent
      composition. Different metastable states were found and examined. Various
      strategies to fold the cyclic, highly hydrogen bonded peptide, starting from
      different nonfolded conformations of the peptide, were investigated. Due to the
      high barriers to (un)folding, a folding/unfolding equilibrium could not be
      established.

PMID- 20055406
TI  - Structure-activity relationship of aliphatic compounds for nematicidal activity
      against pine wood nematode (Bursaphelenchus xylophilus).
AB  - Nematicidal activity of aliphatic compounds was tested to determine a structure
      activity relationship. There was a significant difference in nematicidal activity
      among functional groups. In a test with alkanols and 2E-alkenols, compounds with
      C(8)-C(11) chain length showed 100% nematicidal activity against pine wood
      nematode, Bursaphelenchus xylophilus , at 0.5 mg/mL concentration. C(6)-C(10) 2E
      alkenals exhibited >95% nematicidal activity, but the other compounds with C(11)
      C(14) chain length showed weak activity. Nematicidal activity of alkyl acetates
      with C(7)-C(11) chain length was strong. Compounds belonging to hydrocarbons,
      alkanals, and alkanoic acetates showed weak activity at 0.5 mg/mL concentration.
      Nematicidal activity of active compounds was determined at lower concentrations.
      At 0.25 mg/mL concentration, whole compounds except C(8) alkanol, C(8) 2E
      alkenol, and C(7) alkanoic acid showed >80% nematicidal activity. C(9)-C(11)
      alkanols, C(10)-C(11) 2E-alkenols, C(8)-C(9) 2E-alkenals, and C(9)-C(10) alkanoic
      acids showed >80% nematicidal activity at 0.125 mg/mL concentration. Only C(11)
      alkanol exhibited strong nematicidal activity at 0.0625 mg/mL concentration, the
      lowest concentration that was tested.

PMID- 20055407
TI  - Profiles and some initial identifications of (anti)androgenic compounds in fish
      exposed to wastewater treatment works effluents.
AB  - Exposure of fish to wastewater treatment works (WwTWs) effluents can result in
      reproductive anomalies consistent with exposure to estrogenic compounds. However,
      UK WwTWs effluents also contain compounds with androgen receptor activities which
      may contribute to reproductive dysfunction in fish. A toxicity identification and
      evaluation (TIE) approach was used to profile (anti)androgenic compounds in bile
      of fish exposed to two WwTWs effluents. Extracts of bile from exposed fish and
      effluent were fractionated by liquid chromatography and tested for
      (anti)androgenic activity using a yeast androgen receptor transcription screen
      (YAS). A number of bile fractions contained (anti)androgenic activity unique to
      the effluent-exposed fish. Some of these fractions contained
      di(chloromethyl)anthracene or dichlorophene, and these contaminants showed
      antagonistic activity in the YAS when tested as pure compounds. No androgenic
      activity was detected in the effluents, but TIE analysis of bile revealed a
      number of androgenic fractions which contained testosterone metabolites that were
      unique to effluent-exposed fish. This is the first work reported on the nature of
      some of the (anti)androgenic compounds that bioaccumulate in fish from WwTWs
      effluents and indicates that other contaminants, besides estrogenic substances,
      need to be considered for their potential to contribute to the disruption of
      reproductive system of fish in UK waters.

PMID- 20055408
TI  - Modeling the plant uptake of organic chemicals, including the soil-air-plant
      pathway.
AB  - The soil-air-plant pathway is potentially important in the vegetative
      accumulation of organic pollutants from contaminated soils. While a number of
      qualitative frameworks exist for the prediction of plant accumulation of organic
      chemicals by this pathway, there are few quantitative models that incorporate
      this pathway. The aim of the present study was to produce a model that included
      this pathway and could quantify its contribution to the total plant contamination
      for a range of organic pollutants. A new model was developed from three submodels
      for the processes controlling plant contamination via this pathway: aerial
      deposition, soil volatilization, and systemic translocation. Using the combined
      model, the soil-air-plant pathway was predicted to account for a significant
      proportion of the total shoot contamination for those compounds with log K(OA) >
      9 and log K(AW) < -3. For those pollutants with log K(OA) < 9 and log K(AW) > -3
      there was a higher deposition of pollutant via the soil-air-plant pathway than
      for those chemicals with log K(OA) > 9 and log K(AW) < -3, but this was an
      insignificant proportion of the total shoot contamination because of the higher
      mobility of these compounds via the soil-root-shoot pathway. The incorporation of
      the soil-air-plant pathway into the plant uptake model did not significantly
      improve the prediction of the contamination of vegetation from polluted soils
      when compared across a range of studies. This was a result of the high
      variability between the experimental studies where the bioconcentration factors
      varied by 2 orders of magnitude at an equivalent log K(OA). One potential reason
      for this is the background air concentration of the pollutants under study. It
      was found background air concentrations would dominate those from soil
      volatilization in many situations unless there was a soil hot spot of
      contamination, i.e., >100 mg kg(-1).

PMID- 20055409
TI  - Rheofermentometer fermentation and breadmaking characteristics of dough
      containing xylo-oligosaccharide hydrolyzate from wheat bran.
AB  - The sugar composition of a xylo-oligosaccharide enzymolysis solution (XES)
      hydrolyzed from wheat bran and bread containing XES were studied. The effects of
      the XES on fermentation properties of dough and on bread crumb and crust color
      characteristics are reported. The composition of sugars was determined by high
      performance liquid chromatography (HPLC), and the fermentation properties of
      dough and bread color were determined by Rheofermentometer F3 and Chroma Meter CR
      400, respectively. xylo-Oligosaccharides (XOS) (51.3%) and xylose (39.2%) were
      the major sugars in the XES. XOS remained in the XES-containing bread after
      breadmaking processes (xylotriose, xylotetraose, and xylopentaose, 21.1%), with
      xylopentaose accounting for 14.4%. Maximum dough height (Hm) was significantly
      increased by XES, while the maximum gaseous release height (Hm') was not
      affected. XES increased the brownness index of the crumb and crust of bread when
      compared to the that of control bread. Consumer acceptability scores of control
      and XES containing breads were similar.

PMID- 20055410
TI  - Jam processing and storage effects on blueberry polyphenolics and antioxidant
      capacity.
AB  - Fresh blueberries were processed into sugar and sugar-free jams and stored for 6
      months at 4 and 25 degrees C. The jams were analyzed immediately after processing
      and over 6 months of storage for polyphenolic content, percent polymeric color,
      and antioxidant capacity. Processing resulted in losses of anthocyanins,
      procyanidins, chlorogenic acid, and ORAC in both jam types, but flavonols were
      well retained. Marked losses of anthocyanins and procyanidins occurred over 6
      months of storage and were accompanied by increased polymeric color values.
      Chlorogenic acid levels also declined during storage, but flavonols and ORAC
      changed little. Jams stored at 4 degrees C retained higher levels of
      anthocyanins, procyanidins, and ORAC and had lower polymeric color values than
      jams stored at 25 degrees C. Sugar-free jams retained higher levels of
      anthocyanins and had lower polymeric color values than sugar jams late during
      storage. Blueberry jams should be refrigerated to better retain polyphenolics and
      antioxidant capacity.

PMID- 20055411
TI  - Lipase-catalyzed synthesis of conjugated linoleyl beta-sitosterol and its
      cholesterol-lowering properties in mice.
AB  - Conjugated linoleyl beta-sitosterol (CLS) was prepared from beta-sitosterol and
      conjugated linoleic acid (CLA) via lipase-catalyzed synthesis in n-hexane in the
      presence of molecular sieves. Its plasma cholesterol-lowering properties were
      also studied. The optimal biosynthesis conditions were as follows: beta
      sitosterol concentration of 50 micromol/mL, the molar ratio of CLA to beta
      sitosterol of 1:1, the lipase concentration of 20 mg/mL, and 4 A molecular sieve
      concentration of 60 mg/mL in n-hexane at 50 degrees C with vigorous shaking of
      150 rpm for 72 h, and the highest yield of CLS reached 72.6%. The isolated CLS
      mixed with mice feed had good cholesterol-lowering properties. It decreased serum
      total cholesterol (TC), serum triacylglycerols (TAGs), serum low-density
      lipoprotein cholesterol (LDL-C), atherogenic index (AI), liver weight (LW), liver
      index (LI), liver TC, and TAGs of mice, which was shown that CLS could prevent
      the formation of atherosclerosis and moderate the fat pathologic changes of
      liver. However, the HDL-C was not decreased, which proved the advantage of CLS
      over the other cholesterol-lowering products.

PMID- 20055412
TI  - Preformulation stability of trans-resveratrol and trans-resveratrol glucoside
      (Piceid).
AB  - Resveratrol and resveratrol glucoside (piceid) were evaluated in a preformulation
      stability study. An HPLC assay was used for the analysis of stressed/reference
      samples. Samples of solid, crystalline material were held under the following
      conditions: 40 degrees C/75% RH (both open and protected), ambient fluorescent
      light (open), 70 degrees C (open), and exposed using a light cabinet to achieve
      ICH conditions for UV/fluorescent light. Both compounds were found to be stable
      out to 3 months for both accelerated and ambient conditions with negligible
      degradation. Exposure to UV and fluorescent light under ICH conditions did not
      significantly degrade the solid materials for UV exposure at 3 times the ICH
      limit and for fluorescent light exposure at 1 times the ICH limit. The results
      presented demonstrate crystalline resveratrol and piceid are stable solids. No
      evidence of oxidation of either material by atmospheric oxidants was seen. The
      data reported may help to clarify widely held beliefs that resveratrol is
      unstable and extremely sensitive to oxidation/degradation.

PMID- 20055413
TI  - Volume reduction of nonaqueous media contaminated with a highly halogenated model
      compound using superoxide.
AB  - Highly halogenated organic compounds, which include polychlorinated biphenyls
      (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs) formed during the synthesis
      of pentachlorophenol and chlorophenoxy herbicides, are often found as
      contaminants in less toxic nonaqueous media, such as waste oil, oily sludges, or
      biosolids. Superoxide is highly reactive with halogenated compounds when both are
      dissolved in nonaqueous media; however, superoxide is most economically generated
      in water, where it is unreactive with most organic compounds. Superoxide
      reactivity was investigated in organic solvent-water systems as a basis for
      treating halogenated contaminants in less toxic nonaqueous media. Such a process
      could potentially render a contaminated oil or sludge nonhazardous, providing a
      mechanism for waste volume reduction. Increasing amounts of water added to
      acetone and dimethyl sulfoxide systems decreased the activity of superoxide in
      the solvent, but enough activity remained for effective treatment. Superoxide was
      then generated in the aqueous phase of two-phase water-organic solvent systems,
      and significant superoxide activity was achieved in the organic media with the
      addition of phase transfer catalysts (PTCs) to transfer superoxide into the
      nonaqueous phase. The results of this research demonstrate that superoxide, which
      can be generated in water electrochemically or through the catalytic
      decomposition of peroxygens, has the potential to be transferred to oils,
      sludges, and other less toxic nonaqueous media to destroy highly refractory
      contaminants such as PCBs, PCDDs, and other halogenated contaminants.

PMID- 20055414
TI  - Free amino acids and sugars in rye grain: implications for acrylamide formation.
AB  - Acrylamide forms from free asparagine and sugars during cooking, and products
      derived from the grain of cereals, including rye, contribute a large proportion
      of total dietary intake. In this study, free amino acid and sugar concentrations
      were measured in the grain of a range of rye varieties grown at locations in
      Hungary, France, Poland, and the United Kingdom and harvested in 2005, 2006, and
      2007. Genetic and environmental (location and harvest year) effects on the levels
      of acrylamide precursors were assessed. The data showed free asparagine
      concentration to be the main determinant of acrylamide formation in heated rye
      flour, as it is in wheat. However, in contrast to wheat, sugar, particularly
      sucrose, concentration also correlated both with asparagine concentration and
      with acrylamide formed. Free asparagine concentration was shown to be under
      genetic (G), environmental (E), and integrated (G x E) control. The same was true
      for glucose, whereas maltose and fructose were affected mainly by environmental
      factors and sucrose was largely under genetic control. The ratio of variation due
      to varieties (genotype) to the total variation (a measure of heritability) for
      free asparagine concentration in the grain was 23%. Free asparagine concentration
      was closely associated with bran yield, whereas sugar concentration was
      associated with low Hagberg falling number. Rye grain was found to contain much
      higher concentrations of free proline than wheat grain, and less acrylamide
      formed per unit of asparagine in rye than in wheat flour.

PMID- 20055415
TI  - Comparative study on histological structures of the vitelline membrane of hen and
      duck egg observed by cryo-scanning electron microscopy.
AB  - The histological structures of the vitelline membranes (VM) of hen and duck eggs
      were observed by cryo-scanning electron microscopy (cryo-SEM), and the chemical
      characteristics were also compared. The outer layer surface (OLS) of duck egg VM
      showed networks constructed by fibrils and sheets (0.1-5.2 microm in width), and
      that of hen egg presented networks formed only by sheets (2-6 microm in width).
      Thicker fibrils (0.5-1.5 microm in width) with different arrangement were
      observed on the inner layer surface (ILS) of duck egg VM as compared to those
      (0.3-0.7 microm in width) of hen egg VM. Upon separation, the outer surface of
      the outer layer (OSOL) and the inner surface of the inner layer (ISIL) of hen and
      duck egg VMs were quite similar to fresh VM except that the OSOL of duck egg VM
      showed networks constructed only by sheets. Thin fibrils interlaced above a bumpy
      or flat structure were observed at the exposed surface of the outer layer (ESOL)
      of hen and duck egg VMs. The exposed surfaces of inner layers (ESIL) of hen and
      duck egg VMs showed similar structures of fibrils, which joined, branched, and
      ran in straight lines for long distances up to 30 microm; however, the widths of
      the fibrils shown in ESOL and ESIL of duck egg VM were 0.1 and 0.7-1.4 microm,
      respectively, and were greater than those (<0.1 and 0.5-0.8 microm) of hen egg
      VM. The continuous membranes of both hen and duck egg VMs were still attached to
      the outer layers when separated. The content of protein, the major component of
      VM, was higher in duck egg VM (88.6%) than in hen egg VM (81.6%). Four and six
      major SDS-soluble protein patterns with distinct localization were observed in
      hen and duck egg VMs, respectively. Overall, the different histological
      structures of hen and duck egg VMs were suggested to be majorly attributable to
      the diverse protein components.

PMID- 20055416
TI  - Novel oxadiazole analogues derived from ethacrynic acid: design, synthesis, and
      structure-activity relationships in inhibiting the activity of glutathione S
      transferase P1-1 and cancer cell proliferation.
AB  - Ethacrynic acid (EA) is a glutathione S-transferase P1-1 (GST P1-1) inhibitor
      with weak antiproliferative ability in tumor cells. By use of the principle of
      bioisosterism, a series of novel EA oxadiazole analogues were designed and
      synthesized. The structure-activity relationships of inhibiting GST P1-1 activity
      and cell proliferation of those EA analogues were investigated in human leukemia
      HL-60 cells. Our data revealed that those EA oxadiazole analogues had improved
      antiproliferative activity and most of them had similar or better inhibitory
      effects on GST P1-1 activity than EA. Compound 6u was one of the potent
      antiproliferative agents without inhibition of GST P1-1 activity. Compounds 6r
      and 6s were two potent cell growth inhibitors in several solid tumor cell lines
      with the concentrations inhibiting half of cell growth of less than 5 microM. Our
      data suggest that these EA oxadiazole analogues are promising antitumor agents
      that may act through GST P1-1 inhibition-dependent and/or -independent pathways.

PMID- 20055417
TI  - Synthesis and opioid activity of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a
      octahydro-1H-benzofuro[3,2-e]isoquinolines.
AB  - A series of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H
      benzofuro[3,2-e]isoquinolines was synthesized. The (-)-enantiomers had much
      greater kappa-, mu-, and delta-opioid receptor binding affinity than the
      corresponding (+)-enantiomers. Compounds (-)-1a, (-)-1b, and (-)-1c displayed
      subnanomolar binding affinity for the mu-receptor, and (-)-1b had a high affinity
      for the kappa-receptor. Compound (-)-1a was a mu-partial agonist and kappa
      antagonist. Compound (-)-1b was a potent neutral mu-antagonist (K(d) = 0.22 nM)
      and a kappa-partial agonist.

PMID- 20055418
TI  - Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone
      deacetylase inhibitors as anticancer agents.
AB  - Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid
      hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses
      pancreatic cancer cell growth in vitro with the lowest IC(50) value of 20 nM
      against MiaPaca-2 cell. In this study, we continued our efforts to develop
      triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal
      phenyl ring of 4a with different substituents. The isoform inhibitory profile of
      these hydroxamate analogues was similar to those of 4a. All of these triazol-4
      ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h
      and 11a were found to be very effective inhibitors of cancer cell growth in the
      HupT3 (IC(50) = 50 nM) and MiaPaca-2 (IC(50) = 40 nM) cancer cell lines,
      respectively. Compound 4a was found to reactivate the expression of CDK inhibitor
      proteins and to suppress pancreatic cancer cell growth in vivo. Taken together,
      these data further support the value of the triazol-4-ylphenyl bearing
      hydroxamates in identifying potential pancreatic cancer therapies.

PMID- 20055419
TI  - Amperometric detection of dopamine in vivo with an enzyme based carbon fiber
      microbiosensor.
AB  - We developed a novel implantable enzyme-based carbon fiber biosensor for in vivo
      monitoring of dopamine. The biosensor is fabricated using tyrosinase immobilized
      in a biocompatible matrix consisting of a biopolymer, chitosan and ceria-based
      metal oxides, deposited onto the surface of a carbon fiber microelectrode with a
      diameter of approximately 100 microm. Tyrosinase catalyzes the conversion of
      dopamine to o-dopaquinone, and the reduction of o-dopaquinone, which requires a
      low potential difference, was detected electrochemically. The role of each
      component in the sensing layer was systematically investigated in relation to the
      analytical performance of the biosensor. In its optimal configuration, the
      biosensor demonstrated a detection limit of 1 nM dopamine, a linear range of 5
      orders of magnitude between 10 nM and 220 microM, a sensitivity of 14.2 nA x
      microM(-1), and good selectivity against ascorbic acid, uric acid, serotonin,
      norepinephrine, epinephrine, and 3,4-dihydroxy-l-phenylalanine (L-DOPA). The
      system provided continuous, real time monitoring of electrically stimulated
      dopamine release in the brain of an anesthetized rat. Levels of dopamine up to
      1.69 microM were measured. This new implantable dopamine biosensor provides an
      alternative to fast scan cyclic voltammetry for in vivo monitoring of dopamine.

PMID- 20055421
TI  - Using ac-field-induced electro-osmosis to accelerate biomolecular binding in
      fiber-optic sensing chips with microstructures.
AB  - This article reports the use of ac-field-induced charges at the corners of
      microstructures on fiber-optic sensing chips to generate electro-osmotic vortex
      flows in flow cell channels that can accelerate solute binding on the fiber. The
      sensing chip made of a cyclic olefin copolymer COC substrate contained a flow
      cell channel of dimensions 15 mm x 1 mm x 1 mm. A partially unclad optical fiber
      was placed within the channel. Relief-like strip structures of 25-mum thickness
      fabricated on the channel bottom were produced with an injection-molding process.
      The external electric field lines penetrating through the corners of the plastic
      microstructures induce charges on the corner surfaces to build up electrical
      double layers. When a high-frequency ac field (approximately 100 kHz) is used to
      flip the field polarities quickly, neutralization of the induced charge cannot be
      accomplished. The electrical double layer is therefore sustained. When absorbed
      charges in the double layer are driven by the external field, electro-osmotic
      flows are generated. The unclad portion of the fiber was coated with biotin
      functionalized gold nanoparticles. The streptavidin solution was filled in the
      channel from the feeding tube, and the ac field (approximately 50 V/cm) was
      subsequently turned on for 30 s. The ac-field-induced electro-osmotic flows can
      accelerate solute transport in the sensing channel to enhance the binding
      kinetics of streptavidin molecules with biotin probes implanted on the gold
      nanoparticle surface. As a result, the fiber-optic localized plasmon resonance
      (FO-LPR) sensing signal becomes steady as soon as the external field is turned
      off. In contrast, the signal cannot reach steady state until 200-300 s in a
      typical static sensing cell. A significant reduction in the sensing response time
      is demonstrated. The binding assay of streptavidin with immobilized biotin on
      gold nanoparticle-coated sensing fibers was validated using this mixing device.
      The detection limit for streptavidin of approximately 10(-11) M is close to the
      reported values obtained using static cells. Similarly, the sensing response time
      of an orchid Odontoglossum ringspot virus (ORSV) sample was reduced from 1000 to
      330 s when an external field was applied to mix the fluid for 60 s, even though
      the detection limit was maintained.

PMID- 20055422
TI  - Synthesis, structures, and optical properties of heteroarene-fused dispiro
      compounds.
AB  - Novel heteroarene-fused dispiro compounds, dispiro[9H-fluorene-9,5'(6'H)
      diindeno[1,2-b:2',1'-d]furan-6',9''-[9H]fluorene] (dsp-DIF), dispiro[9H-fluorene
      9,5'(6'H)-diindeno[1,2-b:2',1'-d]thiophene-6',9''-[9H]fluorene] (dsp-DIT), and 11
      phenyldispiro[9H-fluorene-9,5'(6'H)-diindeno[1,2-b:2',1'-d]pyrrole-6',9''
      [9H]fluorene] (dsp-DIP-Ph) have been synthesized. Their structures were
      unambiguously determined by X-ray crystallography. These three dispiro compounds
      showed blue fluorescence with moderate quantum yields.

PMID- 20055423
TI  - Luminescent mononuclear Ag(I)-bis(diphosphine) complexes: correlation between the
      photophysics and the structures of mononuclear Ag(I)-bis(diphosphine) complexes.
AB  - Correlation between the photophysics and the structures of three Ag(I)
      bis(diphosphine) complexes ([Ag(dppbz)(2)]NO(3) (1.NO(3)), [Ag(dppe)(2)]NO(3)
      (2.NO(3)), and [Ag(dppp)(2)]NO(3) (3.NO(3)) (dppbz = 1,2
      bis(diphenylphosphino)benzene, dppe = 1,2-bis(diphenylphosphino)ethane, dppp =
      1,3-bis(diphenylphosphino)propane) has been investigated using temperature
      dependent emission measurements and electrochemical and theoretical methods. All
      three Ag(I)-bis(diphosphine) complexes have relatively low oxidation potential,
      which allows metal-to-ligand charge transfer (MLCT) contribution in the lowest
      excited state of the tetrahedral geometry, which is difficult in other Ag(I)
      complexes. Both 1.NO(3) and 2.NO(3) show orange phosphorescence with moderate
      quantum yield in air-free methanol at room temperature, while 3.NO(3) is less
      emissive in solution at room temperature. In all three complexes the temperature
      dependent luminescence measurements in EtOH/MeOH 4:1 (v/v) solution indicate the
      blue-shift of the emission maximum and the increase of the emission intensity on
      lowering the temperature. In particular, the sequential emission spectral change
      with decreasing temperature is observed in 1.NO(3) and 2.NO(3). In the glass
      state at 90 K, all three complexes show intense blue phosphorescence. The
      theoretical calculation using density functional theory (DFT) suggests that the
      orange and blue emissions mainly originate from the (3)MC excited state based on
      a square-planar geometry and the (3)IL+(3)MLCT excited state based on a
      tetrahedral geometry, respectively.

PMID- 20055424
TI  - Solvatochromic and ionochromic effects of Iron(II)bis(1,10
      phenanthroline)dicyano: a theoretical study.
AB  - Solvatochromic and ionochromic effects of the iron(II)bis(1,10
      phenanthroline)dicyano (Fe(phen)(2)(CN)(2)) complex were investigated by means of
      combined DFT/TDDFT calculations using the PBE and B3LYP functionals. Extended
      solvation models of Fe(phen)(2)(CN)(2) in acetonitrile and aqueous solution, as
      well as including interaction with Mg(2+), were constructed. The calculated
      vertical excitation energies reproduce well the observed solvatochromism in
      acetonitrile and aqueous solutions, the ionochromism in acetonitrile in the
      presence of Mg(2+), and the absence of ionochromic effect in aqueous solution.
      The vertical excitation energies and the nature of the transitions were reliably
      predicted after inclusion of geometry relaxation upon aqueous micro- and global
      solvation and solvent polarization effect in the TDDFT calculations. The two
      intense UV-vis absorption bands occurring for all systems studied are interpreted
      as transitions from a hybrid Fe(II)(d)/cyano N(p) orbital to a phenanthroline pi*
      orbital rather than a pure metal-to-ligand-charge transfer (MLCT). The
      solvatochromic and ionochromic blue band shifts of Fe(phen)(2)(CN)(2) were
      explained with preferential stabilization of the highest occupied Fe(II)(d)/cyano
      N(p) orbitals as a result of specific interactions with water solvent molecules
      or Mg(2+) ions in solution. Such interactions occur through the CN(-) groups in
      the complex, and they have a decisive role for the observed blue shifts of UV-vis
      absorption bands.

PMID- 20055425
TI  - Heat shock protein 90: inhibitors in clinical trials.

PMID- 20055426
TI  - Antiangiogenic effect of dual/selective alpha(5)beta(1)/alpha(v)beta(3) integrin
      antagonists designed on partially modified retro-inverso cyclotetrapeptide
      mimetics.
AB  - Recent evidence highlighted the role of alpha(5)beta(1) integrin in angiogenesis
      and in regulating alpha(v)beta(3) integrin function. As a consequence, selective
      alpha(5)beta(1) integrin inhibitors or dual alpha(5)beta(1)/alpha(v)beta(3)
      integrin inhibitors are considered promising candidates for the development of
      cancer therapeutic agents. In this paper, we describe the synthesis and
      pharmacological characterization of a minilibrary of cyclotetrapeptide mimetics
      containing a PMRI Arg-Gly-Asp sequence. In particular, c[(R)
      betaPhepsi(NHCO)Asppsi(NHCO)Gly-Arg] (3) displayed a good activity in inhibiting
      the alpha(v)beta(3) integrin-mediated cell adhesion of fibronectin or
      vitronectin, as well as the adhesion of fibronectin to the alpha(5)beta(1)
      integrin. Interestingly, the diastereomeric compound c[(S)
      betaPhepsi(NHCO)Asppsi(NHCO)Gly-Arg] (2) maintained a good efficacy in inhibiting
      alpha(5)beta(1) integrin while gaining a certain selectivity over alpha(v)beta(3)
      integrin. These two integrin antagonists significantly inhibited bFGF-induced
      human endothelial cell tube formation at submicromolar concentrations.
      Conformational analysis and Molecular Docking calculations suggest that the
      different alpha(5)beta(1) versus alpha(v)beta(3) selectivity of 2 and 3 can be
      rationalized on the basis of the alternative display of the aromatic side chain
      adjacent to Asp.

PMID- 20055427
TI  - Fructose-1,6-bisphosphatase Inhibitors. 2. Design, synthesis, and structure
      activity relationship of a series of phosphonic acid containing benzimidazoles
      that function as 5'-adenosinemonophosphate (AMP) mimics.
AB  - Efforts to enhance the inhibitory potency of the initial purine series of
      fructose-1,6-bisphosphatase (FBPase) inhibitors led to the discovery of a series
      of benzimidazole analogues with human FBPase IC(50)s < 100 nM. Inhibitor 4.4
      emerged as a lead compound based on its potent inhibition of human liver FBPase
      (IC(50) = 55 nM) and significant glucose lowering in normal fasted rats.
      Intravenous administration of 4.4 to Zucker diabetic fatty rats led to rapid and
      robust glucose lowering, thereby providing the first evidence that FBPase
      inhibitors could improve glycemia in animal models of type 2 diabetes.

PMID- 20055428
TI  - Titanocene difluorides with improved cytotoxic activity.
AB  - Titanocene difluorides can be obtained by halide metathesis of the respective
      titanocene dichlorides with trimethyltin fluoride (Me(3)SnF), giving access to a
      new class of cytotoxic active substances. Furthermore, an improved method for the
      synthesis of diaryl-substituted titanocene dichlorides is presented.

PMID- 20055429
TI  - Possibilities for titanium-titanium multiple bonding in binuclear
      cyclopentadienyltitanium carbonyls: 16-electron metal configurations and four
      electron donor bridging carbonyl groups as alternatives.
AB  - The structures for the binuclear Cp(2)Ti(2)(CO)(n) derivatives (Cp = eta(5)
      C(5)H(5); n = 8, 7, 6, 5, 4, 3, 2) have been optimized using density functional
      theory. Furthermore, the thermodynamics of CO dissociation, disproportionation
      into Cp(2)Ti(2)(CO)(n+1) + Cp(2)Ti(2)(CO)(n-1), and dissociation into mononuclear
      fragments of these Cp(2)Ti(2)(CO)(n) derivatives have been studied. An unbridged
      Cp(2)Ti(2)(CO)(8) structure with a long approximately 3.9 A Ti-Ti bond is found.
      As expected from the long Ti-Ti bond, the predicted dissociation energy of this
      dimer into CpTi(CO)(4) fragments is relatively low at 7 +/- 3 kcal/mol. The
      lowest energy Cp(2)Ti(2)(CO)(6) structure has two CpTi(CO)(3) units linked by a
      formal approximately 2.8 A Ti identical withTi triple bond and thus is the next
      member of the M identical withM triply bonded series Cp(2)V(2)(CO)(5),
      Cp(2)Cr(2)(CO)(4), Cp(2)Mn(2)(CO)(3), all three of which are stable compounds.
      The lowest energy structures of Cp(2)Ti(2)(CO)(7), Cp(2)Ti(2)(CO)(5), and
      Cp(2)Ti(2)(CO)(4) all contain one or two four-electron donor bridging eta(2)-mu
      CO groups. However, they are not likely to be stable molecules since their
      disproportionation energies into Cp(2)Ti(2)(CO)(n+1) + Cp(2)Ti(2)(CO)(n-1) are
      either nearly thermoneutral (n = 5) or exothermic (n = 7 and 4). The lowest
      energy structure of Cp(2)Ti(2)(CO)(3), in which all three carbonyl groups are
      four-electron donor eta(2)-mu-CO groups bridging a approximately 3.05 A formal Ti
      Ti single bond, is a promising synthetic target since it is thermodynamically
      stable with respect to both CO dissociation and disproportionation into
      Cp(2)Ti(2)(CO)(4) + Cp(2)Ti(2)(CO)(2). In the lowest energy Cp(2)Ti(2)(CO)(2)
      structure both carbonyl groups are four-electron donor eta(2)-mu-CO groups
      bridging a formal 2.74 A Ti[triple bond]Ti triple bond. These low energy
      Cp(2)Ti(2)(CO)(n) (n = 3, 2) structures have only a 16-electron titanium
      configuration rather than the usually favorable 18-electron configuration for
      metal carbonyl complexes.

PMID- 20055430
TI  - Anomalously large reactivity of single graphene layers and edges toward electron
      transfer chemistries.
AB  - The reactivity of graphene and its various multilayers toward electron transfer
      chemistries with 4-nitrobenzene diazonium tetrafluoroborate is probed by Raman
      spectroscopy after reaction on-chip. Single graphene sheets are found to be
      almost 10 times more reactive than bi- or multilayers of graphene according to
      the relative disorder (D) peak in the Raman spectrum examined before and after
      chemical reaction in water. A model whereby electron puddles that shift the Dirac
      point locally to values below the Fermi level is consistent with the reactivity
      difference. Because the chemistry at the graphene edge is important for
      controlling its electronic properties, particularly in ribbon form, we have
      developed a spectroscopic test to examine the relative reactivity of graphene
      edges versus the bulk. We show, for the first time, that the reactivity of edges
      is at least two times higher than the reactivity of the bulk single graphene
      sheet, as supported by electron transfer theory. These differences in electron
      transfer rates may be important for selecting and manipulating graphitic
      materials on-chip.

PMID- 20055431
TI  - Extensively chaotic motion in electrostatically driven nanowires and
      applications.
AB  - We carry out a detailed bifurcation analysis for a common class of
      electrostatically driven nanowires in a multiphysics model. A finding is that the
      nanoscale system can exhibit distinct chaotic states: chaos with symmetry
      breaking and extensive chaos possessing the full symmetry of the system.
      Potential applications such as nanoscale random number generator and controlling
      extensive chaos to achieve desirable performance are articulated.

PMID- 20055432
TI  - Two-stage capture employing active transport enables sensitive and fast
      biosensors.
AB  - Nanoscale sensors enable the detection of analytes with improved signal-to-noise
      ratio but suffer from mass transport limitations. Molecular shuttles, assembled
      from, e.g., antibody-functionalized microtubules and kinesin motor proteins, can
      selectively capture analytes from solution and deliver the analytes to a sensor
      patch. This two-stage process can accelerate mass transport to nanoscale
      biosensors and facilitate the rapid detection of analytes. Here, the possible
      increase of the signal-to-noise ratio is calculated, and the optimal layout of a
      system which integrates active transport is determined.

PMID- 20055433
TI  - Anchoring semiconductor and metal nanoparticles on a two-dimensional catalyst
      mat. Storing and shuttling electrons with reduced graphene oxide.
AB  - Using reduced graphene oxide (RGO) as a two-dimensional support, we have
      succeeded in selective anchoring of semiconductor and metal nanoparticles at
      separate sites. Photogenerated electrons from UV-irradiated TiO(2) are
      transported across RGO to reduce silver ions into silver nanoparticles at a
      location distinct from the TiO(2) anchored site. The ability of RGO to store and
      shuttle electrons, as visualized via a stepwise electron transfer process,
      demonstrates its capability to serve as a catalyst nanomat and transfer electrons
      on demand to adsorbed species. These findings pave the way for the development of
      next generation catalyst systems and can spur advancements in graphene-based
      composites for chemical and biological sensors.

PMID- 20055434
TI  - DNA-damaging, mutagenic, and clastogenic activities of gentiopicroside isolated
      from Cephalaria kotschyi roots.
AB  - Gentiopicroside (1) is the major secoiridoid glucoside constituent of Cephalaria
      kotschyi roots. The mutagenicity, DNA-damaging capacities, and clastogenicity of
      this molecule were evaluated by the Salmonella typhimurium mutagenicity assay
      (Ames test) on tester strains TA97a, TA98, TA100, and TA102, the alkaline comet
      assay, and the micronucleus assay on CHO cells. All tests were performed with and
      without the metabolization mixture, S9 mix. In the Ames test, the mutagenicity of
      1 was limited to TA102 without S9 mix (2.3 rev microg(-1)). The genotoxicity was
      more evident without S9 mix (0.78 OTMchi(2) units microg(-1) mL) than with the
      metabolic mixture (0.16 OTMchi(2) units microg(-1) mL) with the comet assay.
      Similarly, the clastogenicity without S9 mix was 0.99 MNC microg(-1) mL and 0.38
      MNC microg(-1) mL with S9 mix in the micronucleus assay. The interaction of 1
      with DNA is probably through the involvement of oxidative DNA lesions.

PMID- 20055435
TI  - Half-solidity of tetrahedral-like Al(55) clusters.
AB  - A new dynamic melting state, which has both solid and liquid characteristics, is
      revealed from first-principles molecular dynamics simulations of Al(55) clusters.
      In thermal fluctuations near the melting point, the low-energy tetrahedral-like
      Al(55) survives through rapid, collective surface transformations-such as parity
      conversions and correlated diffusion of two distant vacancies-without losing its
      structural orders. The emergence of the collective motions is solely due to
      efficient thermal excitation of soft phonon modes at nanoscale. A series of
      spontaneous surface reconfigurations result in a mixture or effective flow of
      surface atoms as is random color shuffling of a Rubik's cube. This novel flexible
      solid state (termed as half-solidity) provides useful insights into understanding
      stability, flexibility, and functionality of nanosystems near or below melting
      temperatures.

PMID- 20055436
TI  - Emergent complexity from simple anisotropic building blocks: shells, tubes, and
      spirals.
AB  - We describe a remarkably simple, generic, coarse-grained model involving
      anisotropic interactions, and characterize the global minima for clusters as a
      function of various parameters. Appropriate choices for the anisotropic
      interactions can reproduce a wide variety of complex morphologies as global
      minima, including spheroidal shells, tubular, helical and even head-tail
      morphologies, elucidating the physical principles that drive the assembly of
      these mesoscopic structures. Our model captures several experimental
      observations, such as the existence of competing morphologies, capsid
      polymorphism, and the effect of scaffolding proteins on capsid assembly.

PMID- 20055438
TI  - Capillarity-assisted assembly of carbon nanotube microstructures with organized
      initiations.
AB  - In this work, detailed studies of three different capillary-assisted techniques
      for the formations of large-scale multiwalled carbon-nanotube (MWNT)-based
      microstructures were presented. Using laser induced artificial vacancies, new
      insights into the effect of laser power, densities of MWNTs, and oxidation
      process dependencies for the creations of MWNT polygons were presented. With
      organized initiations, MWNT pillars were crafted out of MWNT arrays and 0.21 pL
      of water was found to produce sufficient force to bring about 14.7 mum
      deflections of a 9.19 x 9.19 x 24.1 mum(3) pillar, thereby allowing well
      controlled formations of three-dimensional top-gathering MWNTs. Lastly, by
      twisting densified MWNT microbelts, 14 times improvements in resistivity as
      compared to undensified MWNT microwalls were achieved. Through prepatterning, the
      amount of twisting effect could be controlled, and this in turn allowed control
      of the resistance of the densified MWNT microwalls. These new insights and
      techniques presented could further encourage the use of self-organized MWNT
      structures with initiation as a flexible and viable route for the implementations
      of carbon-nanotube-based electronic devices.

PMID- 20055437
TI  - Biochemical analysis of phenotypic diversity associated with mutations in codon
      244 of the retinal degeneration slow gene.
AB  - Mutations in the protein product of the retinal degeneration slow (RDS) gene
      cause both rod-dominant retinitis pigmentosa and different forms of cone-dominant
      macular dystrophies. In particular, mutations in codon 244 can cause either of
      these types of disease. In this study, we examine the biochemical effects of
      N244H and N244K in an effort to understand the mechanism underlying rod- and cone
      dominant defects, respectively. COS-1 cells were cotransfected with either wild
      type (WT) RDS or RDS containing an N244H or N244K mutation along with its binding
      partner, ROM-1 (rod outer segment membrane protein 1). Cell extracts were
      analyzed for mutant protein stability by Western blot, and localization was
      examined by immunocytochemistry. Interactions between transfected proteins were
      assessed by reciprocal co-immunoprecipitation, and nonreducing velocity
      sedimentation was used to identify the pattern of RDS complex assembly.
      Interactions were confirmed using GST fusion constructs of WT and mutant RDS in
      GST pull-down assays from WT mouse retinal extract. In COS-1 cells, recombinant
      N244H RDS had a weakened ability to assemble into higher-order complexes but
      retained the ability to co-immunoprecipitate with ROM-1 as well as localize
      properly throughout the cells. In contrast, recombinant N244K protein did not
      associate with ROM-1, showed signs of protein aggregation, and colocalized with
      an ER marker. These experiments support the hypothesis that RDS mutations that
      interrupt higher-order oligomer formation but still interact with ROM-1 and fold
      properly in membranes may cause dominant, gain-of-function disease phenotypes
      while mutations that cause RDS misfolding (and thus incorrect trafficking and
      assembly) may be associated with a loss-of-function haploinsufficiency phenotype.

PMID- 20055439
TI  - Nanoscale control of optical heating in complex plasmonic systems.
AB  - We introduce a numerical technique to investigate the temperature distribution in
      arbitrarily complex plasmonic systems subject to external illumination. We
      perform both electromagnetic and thermodynamic calculations based upon a time
      efficient boundary element method. Two kinds of plasmonic systems are
      investigated in order to illustrate the potential of such a technique. First, we
      focus on individual particles with various morphologies. In analogy with
      electrostatics, we introduce the concept of thermal capacitance. This geometry
      dependent quantity allows us to assess the temperature increase inside a
      plasmonic particle from the sole knowledge of its absorption cross section. We
      present universal thermal-capacitance curves for ellipsoids, rods, disks, and
      rings. Additionally, we investigate assemblies of nanoparticles in close
      proximity and show that, despite its diffusive nature, the temperature
      distribution can be made highly non-uniform even at the nanoscale using plasmonic
      systems. A significant degree of nanoscale control over the individual
      temperatures of neighboring particles is demonstrated, depending on the external
      light wavelength and direction of incidence. We illustrate this concept with
      simulations of gold sphere dimers and chains in water. Our work opens new
      possibilities for selectively controlling processes such as local melting for
      dynamic patterning of textured materials, chemical and metabolic thermal
      activation, and heat delivery for producing mechanical motion with spatial
      precision in the nanoscale.

PMID- 20055440
TI  - Synthesis and magnetic properties of orthogonally linked phenothiazine cation
      radical dimer and tetramer.
AB  - A 3,3'-orthogonally linked phenothiazine cation radical dimer with methyl
      substituents at the 2, 2', 4, and 4' positions was synthesized. The dimer was
      isolated as a stable product which exists in a triplet state due to a torsion
      angle of ca. 80 degrees between the two phenothiazine units. The tetramer was
      also synthesized by linking the dimers using a 1,4-phenylene spacer.

PMID- 20055441
TI  - Catalytic (asymmetric) methylene transfer to aldehydes.
AB  - An investigation into the poor activity of sulfides as catalysts for sulfonium
      ylide-mediated methylene transfer to aldehydes has indicated that ylide formation
      is the problematic catalytic cycle step. Alkylation with traditional
      electrophiles does not proceed with sufficient efficiency to allow the sulfide to
      be used catalytically. Methyl triflate rapidly alkylates cyclic thiolanes under
      mild conditions, allowing their use in efficient aldehyde epoxidation reactions
      (in conjunction with phosphazene bases) at loadings as low as 10 mol %.

PMID- 20055442
TI  - Enantioselective desymmetrization of diphenylphosphinamides via (-)-sparteine
      mediated ortho-lithiation. Synthesis of P-chiral ligands.
AB  - Asymmetric ortho-lithiation of N-dialkyl-P,P-diphenylphosphinamides using [n
      BuLi.(-)-sparteine] is described as an efficient method for the synthesis of P
      chiral ortho-functionalized derivatives in high yields and ee's from 45 to >99%.
      The method allows access to new enantiomerically pure P-chiral phosphine and
      diimine ligands.

PMID- 20055443
TI  - Phenolic characterization of malbec wines from mendoza province (Argentina).
AB  - Malbec is a wine grape variety that is now mainly produced in Mendoza and
      considered to be the emblematic cultivar of Argentina. Forty-four phenolic
      compounds, including hydroxybenzoic and hydroxycinnamic acids and different
      flavonoids, were identified and quantified in 61 monovarietal Malbec wines from
      11 geographical zones of Mendoza province, using a reversed phase high
      performance liquid chromatography system coupled to a diode array detector (HPLC
      DAD). Among non-flavonoids, gallic, cis-caftaric, trans-coutaric, and caffeic
      acids presented the higher concentrations in all of the samples, whereas trans
      resveratrol glucoside was present at concentrations from 0.6 to 1.3 mg/L. For the
      flavonoids, (+)-catechin and (-)-epicatechin presented the higher concentrations
      among flavan-3-ols with a ratio (+)-catechin/(-)-epicatechin from 1.3 to 2.1. An
      astilbin derivative and quercetin presented the higher concentrations for
      flavonols, whereas malvidin-3-glucoside and its derivatives were the major
      anthocyanins. For the first time the phenolic composition of Malbec wines from
      Mendoza province has been characterized.

PMID- 20055444
TI  - Exploring Morita-Baylis-Hillman reactions of p-quinols.
AB  - The Morita-Baylis-Hillman reaction of p-methylquinols with activated aromatic
      aldehydes has been studied. Depending on the reaction conditions (solvent and
      additives), three different products were formed. A mono or double Morita-Baylis
      Hillman adduct and a fused 1,3-dioxolane could be obtained in good chemical
      yields. The use of non-nucleophilic bases to promote the reaction suggested an
      autocatalytic mechanism.

PMID- 20055445
TI  - Controlling hydrogen scrambling in multiply charged protein ions during
      collisional activation: implications for top-down hydrogen/deuterium exchange MS
      utilizing collisional activation in the gas phase.
AB  - Hydrogen exchange in solution combined with ion fragmentation in the gas phase
      followed by MS detection emerged in recent years as a powerful tool to study
      higher order protein structure and dynamics. However, a certain type of ion
      chemistry in the gas phase, namely, internal rearrangement of labile hydrogen
      atoms (the so-called hydrogen scrambling), is often cited as a factor limiting
      the utility of this experimental technique. Although several studies have been
      carried out to elucidate the roles played by various factors in the occurrence
      and the extent of hydrogen scrambling, there is still no consensus as to what
      experimental protocol should be followed to avoid or minimize it. In this study
      we employ fragmentation of mass-selected subpopulations of protein ions to assess
      the extent of internal proton mobility prior to dissociation. A unique advantage
      of tandem MS is that it not only provides a means to map the deuterium content of
      protein ions whose overall levels of isotope incorporation can be precisely
      defined by controlling the mass selection window, but also correlates this
      spatial isotope distribution with such global characteristic as the protein ion
      charge state. Hydrogen scrambling does not occur when the charge state of the
      precursor protein ions selected for fragmentation is high. Fragment ions derived
      from both N- and C-terminal parts of the protein are equally unaffected by
      scrambling. However, spatial distribution of deuterium atoms obtained by
      fragmenting low-charge-density protein ions is consistent with a very high degree
      of scrambling prior to the dissociation events. The extent of hydrogen scrambling
      is also high when multistage fragmentation is used to probe deuterium
      incorporation locally. Taken together, the experimental results provide a
      coherent picture of intramolecular processes occurring prior to the dissociation
      event and provide guidance for the design of experiments whose outcome is
      unaffected by hydrogen scrambling.

PMID- 20055446
TI  - Distribution of volatile composition in 'marion' ( rubus species hyb) blackberry
      pedigree.
AB  - The distribution of volatile constituents in ancestral genotypes of 'Marion'
      blackberry's pedigree was investigated over two growing seasons. Each genotype in
      the pedigree had a specific volatile composition. Red raspberry was dominated by
      norisoprenoids, lactones, and acids. 'Logan' and 'Olallie' also had a
      norisoprenoid dominance but at much lower concentrations. The concentration of
      norisoprenoids in other blackberry genotypes was significantly lower. Terpenes
      and furanones were predominant in wild 'Himalaya' blackberry, whereas terpenes
      were the major volatiles in 'Santiam'. 'Marion', a selection from 'Chehalem' and
      'Olallie', contained almost all of the volatile compounds in its pedigree at
      moderate amount. The chiral isomeric ratios of 11 pairs of compounds were also
      studied. Strong chiral isomeric preference was observed for most of the chiral
      compounds, and each cultivar had its unique chiral isomeric distribution. An
      inherent pattern was observed for some volatile compounds in the 'Marion'
      pedigree. Raspberry and 'Logan' had a very high concentration of beta-ionone, but
      was reduced by half in 'Olallie' and by another half in 'Marion' as the crossing
      proceeded. A high content of linalool in 'Olallie' and a low content in
      'Chehalem' resulted in a moderate content of linalool in their progeny 'Marion'.
      However, the concentration of furaneol in 'Marion' was higher than in its
      parents. A high content of (S)-linalool in 'Olallie' and a racemic content of (S)
      ,(R)-linalool in 'Chehalem' resulted in a preference for the (S)-form in
      'Marion'.

PMID- 20055447
TI  - Modulation of buried ionizable groups in proteins with engineered surface charge.
AB  - Recent work has shown that proteins can tolerate hydrophobic-to-ionizable-residue
      mutations. Here, we provide experimental evidence that the essential properties
      (pK value, protonation state, local dynamics) of buried ionizable groups in
      proteins can be efficiently modulated through the rational design of the surface
      charge distribution, thus paving the way for the protein engineering exploitation
      of charge burial.

PMID- 20055448
TI  - Charge detector for the measurement of ionic solutes.
AB  - We describe a flow-through ionic charge detector in the form of a three
      compartmented system. A central water channel is separated from two outer
      channels bearing water (or a dilute electrolyte) by a cation-exchange membrane
      (CEM) and an anion-exchange membrane (AEM). Independent fluid input/output ports
      address all channels. One platinum electrode is put in each outer channel. When
      the AEM-side electrode is positive with respect to the CEM-side electrode and
      voltage (approximately 1-10 V) is applied, the observed background current is
      from the transport of H(+)/OH(-) through the CEM/AEM to the negative/positive
      electrodes, respectively. The H(+) and OH(-) are generated by the ionization of
      water, in part aided by the electric field. If an electrolyte (X(+)Y(-)) is
      injected in to the central channel, X(+) and Y(-) migrate through the CEM and AEM
      to the negative and positive electrodes, respectively, and generate a current
      pulse. The integrated area of the current signal (coulombs) elicited by this
      electrolyte injection is dependent on a number of variables, the most important
      being the central channel residence time and the applied voltage (V(app)); these
      govern the transport of the injected electrolyte to/through the membranes. Other
      parameters include electrode placement, fluid composition, and outer channel flow
      rates. For strong electrolytes, depending on the operating conditions, the
      current peak area (hereinafter called the measured charge signal, Q(m)) can both
      be less or more than the charge represented by the electrolyte injected (Q(i)).
      Q(m) is less than Q(i) if transport to/through the membranes is subquantitative.
      Q(m) can be greater than Q(i) at higher V(app). At constant V(app) more voltage
      is dropped across the membranes as the central channel becomes more conductive
      and water dissociation at the membrane surface is enhanced. Effectively, the
      membranes experience a greater applied voltage as the central channel becomes
      more conductive. The resulting additional current accompanying analyte
      introduction to the detector can substantially augment Q(m). Thus, the device is
      not an absolute coulometer although V(app) can be deliberately chosen to have
      Q(m) = Q(i) over at least a 10-fold concentration range. Importantly, equivalent
      amounts of diverse strong electrolytes (with substantially different
      conductivities) injected into the central channel produce the same charge
      signals. In ion chromatography, this results in identical calibration curves for
      all strong acid anions, obviating individual calibrations. Whereas with a
      conductivity detector (CD) only the ionized portion of a weak electrolyte
      responds, in the present charge detector (ChD), ions are actually removed,
      leading to further ionization and the detection of a proportionately greater
      analyte amount.

PMID- 20055449
TI  - Carbon nanohorn sensitized electrochemical immunosensor for rapid detection of
      microcystin-LR.
AB  - A sensitive electrochemical immunosensor was proposed by functionalizing single
      walled carbon nanohorns (SWNHs) with analyte for microcystin-LR (MC-LR)
      detection. The functionalization of SWNHs was performed by covalently binding MC
      LR to the abundant carboxylic groups on the cone-shaped tips of SWNHs in the
      presence of linkage reagents and characterized with Raman spectroscopy, X-ray
      photoelectron spectroscopy, scanning electron microscopy, and a transmission
      electron micrograph. Compared with single-walled carbon nanotubes, SWNHs as
      immobilization matrixes showed a better sensitizing effect. Using home-prepared
      horseradish peroxidase-labeled MC-LR antibody for the competitive immunoassay,
      under optimal conditions, the immunosensor exhibited a wide linear response to MC
      LR ranging from 0.05 to 20 microg/L with a detection limit of 0.03 microg/L at a
      signal-to-noise of 3. This method showed good accuracy, acceptable precision, and
      reproducibility. The assay results of MC-LR in polluted water were in a good
      agreement with the reference values. The proposed strategy provided a
      biocompatible immobilization and sensitized recognition platform for analytes as
      small antigens and possessed promising application in food and environmental
      monitoring.

PMID- 20055450
TI  - The role of the chromophore in the biological photoreceptor phytochrome: an
      approach using chemically synthesized tetrapyrroles.
AB  - In plants and bacteria, phytochromes serve as light-inducible, red-/far-red light
      sensitive photoreceptors that control a wide range of photomorphogenetic
      processes. Phytochromes comprise a protein moiety and a covalently bound bilin
      chromophore. Bilins are open-chain tetrapyrrole compounds that derive
      biosynthetically from ubiquitous porphyrins. The investigations of phytochromes
      reveal that precise interactions between the protein moiety and its bilin
      chromophore are essential for the proper functioning of this photoreceptor;
      accordingly, synthetic manipulation of the parts is an important method for
      studying the whole. Although variations in the protein structure are readily
      accomplished by routine mutagenesis protocols, the generation of structurally
      modified bilins is a laborious, multistep process. Recent improvement in the
      synthesis of open-chain tetrapyrroles now permits the generation of novel,
      structurally modified (and even selectively isotope-labeled) chromophores.
      Furthermore, by using the capability of recombinant apo-phytochrome to bind the
      chromophore autocatalytically, researchers can now generate novel chromoproteins
      with modified functions. In the protein-bound state, the phytochrome chromophore
      is photoisomerized at one double bond, in the bridge between the last two of the
      four pyrrole rings (the C and D rings), generating the thermally stable,
      physiologically active P(fr) form. This conversion--photoisomerization from the
      form absorbing red light (P(r)) to the form absorbing far-red light (P(fr))-
      covers 12 orders of magnitude, from subpicoseconds to seconds. Such spectroscopic
      and kinetic studies yield a wealth of time-resolved spectral data, even more so,
      if proteins with changed sequence or chromophore structure are utilized. In
      particular, bilins with a changed substitution pattern at the photoisomerizing
      ring D have shed light on the chromophore-protein interactions during the
      photoisomerization. The mechanisms generating and stabilizing the light-induced
      P(fr) form of phytochromes are now seen in greater detail. On the other hand, the
      use of bilins with selective incorporation of stable isotopes identify light
      induced conformational motions when studied by vibrational (FTIR and Raman) and
      NMR spectroscopy. In this Account, we present spectroscopic investigations that
      provide structural details in these biological photoreceptors with great
      precision and document the dynamics elicited by light excitation. This approach
      yields important information that complements the data deduced from crystal
      structure.

PMID- 20055452
TI  - DNA modifications by the omega-3 lipid peroxidation-derived mutagen 4-oxo-2
      hexenal in vitro and their analysis in mouse and human DNA.
AB  - 4-Oxo-2-hexenal (4-OHE), which forms a 2'-deoxyguanosine (dG) adduct in a model
      lipid peroxidation system, is mutagenic in the Ames test. It is generated by the
      oxidation of omega-3 fatty acids and is commonly found in dietary fats, such as
      fish oil, perilla oil, rapeseed oil, and soybean oil. 4-OHE also forms adducts
      with 2'-deoxyadenosine (dA), 2'-deoxycytidine (dC), and 5-methyl-2'-deoxycytidine
      (5-Me-dC) in DNA. In this study, we characterized the structures of these adducts
      in detail. We measured the amounts of 4-OHE-DNA adducts in mouse organs by
      LC/MS/MS, after 4-OHE was orally administered to mice. The 4-OHE-dA, 4-OHE-dC, 4
      OHE-dG, and 4-OHE-5-Me-dC adducts were detected in stomach and intestinal DNA in
      the range of 0.25-43.71/10(8) bases. After the 4-OHE administration, the amounts
      of these DNA adducts decreased gradually over 7 days. We also detected 4-OHE-dC
      in human lung DNA, in the range of 2.6-5.9/10(9) bases. No difference in the 4
      OHE adduct levels was detected between smokers and nonsmokers. Our results
      suggest that 4-OHE-DNA adducts are formed by endogenous as well as environmental
      lipid peroxides.

PMID- 20055451
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin upregulates FoxQ1b in zebrafish jaw
      primordium.
AB  - Vertebrate jaw development can be disrupted by exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-a potent activator of the aryl hydrocarbon
      receptor (AHR) transcription factor required for transducing the toxic effects of
      TCDD. We used zebrafish (Danio rerio) embryos to investigate transcriptional
      responses to TCDD with the goal of discovering novel, jaw-specific genes affected
      by TCDD exposure. Our results uncovered a novel target of TCDD-activated Ahr
      belonging to the evolutionarily conserved family of forkhead box transcription
      factors. Quantitative real-time polymerase chain reaction analysis demonstrated
      that FoxQ1b was upregulated by TCDD 7- and 10-fold at 24 and 48 h
      postfertilization (hpf), respectively. The rate of TCDD-induced FoxQ1b expression
      was more rapid than that of Cyp1a, a known direct target of TCDD-activated Ahr.
      TCDD-mediated induction of FoxQ1b was suppressed in the presence of an Ahr
      antagonist, alpha-naphthoflavone, as well as following knockdown of Ahr2
      expression using an Ahr2-specific morpholino antisense oligonucleotide. In situ
      hybridization analysis of FoxQ1b expression at 48 hpf demonstrated that FoxQ1b is
      specifically expressed in the jaw primordium where it discretely outlines a
      developing jaw structure known as Meckel's cartilage--a conserved structure in
      all jawed vertebrates that develops abnormally in the presence of TCDD. These
      results identify a novel target of TCDD-activated Ahr and suggest that FoxQ1b may
      play a role in craniofacial abnormalities induced by developmental exposure to
      TCDD.

PMID- 20055453
TI  - Rational design of indoleamine 2,3-dioxygenase inhibitors.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an important therapeutic target for the
      treatment of diseases such as cancer that involve pathological immune escape. We
      have used the evolutionary docking algorithm EADock to design new inhibitors of
      this enzyme. First, we investigated the modes of binding of all known IDO
      inhibitors. On the basis of the observed docked conformations, we developed a
      pharmacophore model, which was then used to devise new compounds to be tested for
      IDO inhibition. We also used a fragment-based approach to design and to optimize
      small organic molecule inhibitors. Both approaches yielded several new low
      molecular weight inhibitor scaffolds, the most active being of nanomolar potency
      in an enzymatic assay. Cellular assays confirmed the potential biological
      relevance of four different scaffolds.

PMID- 20055454
TI  - Formal synthesis of belactosin A and hormaomycin via a diastereoselective
      intramolecular cyclopropanation of an alpha-nitro diazoester.
AB  - An efficient and convenient methodology for the synthesis of the 3-(trans-2
      aminocyclopropyl) alanine and 3-(trans-2-nitrocyclopropyl) alanine moieties found
      in the core of belactosin A and hormaomycin, respectively, is reported. By using
      an enantioenriched substituted alpha-nitro diazoester in a diastereoselective
      intramolecular cyclopropanation reaction, the trans-nitrocyclopropyl alanine
      moiety can be obtained efficiently in five steps from the initial alpha
      nitrocyclopropyl lactone unit, thus achieving the synthesis of the cyclopropane
      core of the two natural products.

PMID- 20055455
TI  - Boronic Acid catalyzed friedel-crafts reactions of allylic alcohols with electron
      rich arenes and heteroarenes.
AB  - Pentafluorophenylboronic acid catalyzes the regioselective coupling of
      structurally diverse allylic alcohols with a variety of electron-rich aromatic
      and heteroaromatic substrates under ambient conditions. The commercially
      available catalyst is recoverable and air and moisture stable, and the reaction
      produces water as the only byproduct.

PMID- 20055456
TI  - Alteration of the substrate's prefolded conformation and cyclization
      stereochemistry of oxidosqualene-lanosterol cyclase of Saccharomyces cerevisiae
      by substitution at phenylalanine 699.
AB  - The Saccharomyces cerevisiae ERG7(Phe699) mutants produced one chair-chair-chair
      (C-C-C) and two chair-boat-chair (C-B-C) truncated tricyclic compounds, one
      tetracyclic 17alpha-exocyclic unrearranged intermediate, and two 17beta-exocyclic
      truncated rearranged intermediates. These results provided direct evidence for
      the importance of the residue in affecting mechanistic transitions between C-B-C
      and C-C-C substrate conformation and between the 17alpha- and 17beta-exocyclic
      side chain stereochemistry as well as in stabilizing the 6-6-5 tricyclic and the
      protosteryl C-17 cations.

PMID- 20055457
TI  - Stereoselective synthesis of 3-aryloctahydroindoles and application in a formal
      synthesis of (-)-pancracine.
AB  - A stereoselective synthesis of 3-aryloctahydroindoles from enantiomerically
      enriched gamma-nitroketones has been developed. Reduction of imines derived form
      the nitroketones provides the trans-fused octhaydroindole motif selectively. The
      cis-octahydroindole skeleton is accessible by an invertive cyclization strategy
      involving a diastereomerically pure nitromesylate intermediate. This approach was
      employed in the synthesis of an advanced intermediate to (-)-pancracine. The
      gamma-nitroketone starting materials are readily available via an organocatalytic
      Michael reaction.

PMID- 20055458
TI  - Exploiting the interaction of metal ions and peptide nucleic acids-DNA duplexes
      for the detection of a single nucleotide mismatch by electrochemical impedance
      spectroscopy.
AB  - The interaction of the metal ions Mg(2+), Zn(2+), Ni(2+), and Co(2+) with DNA
      peptide nucleic acid (PNA) films on a gold surface is studied by electrochemical
      impedance spectroscopy in the presence of [Fe(CN)(6)](3-/4-) as the redox probe.
      Impedance data were analyzed with the help of a modified Randles' equivalent
      circuit. Changes in the charge-transfer resistance, R(CT), decreases in the order
      of Ni(2+) > Co(2+) > Zn(2+) > Mg(2+). We interpret these results in terms of
      stronger interactions for Ni(2+) with the DNA-PNA film compared to the other
      metal ions, potentially involving interactions with the nucleobases, presumably
      with the N7 of purines or the N3 of pyrimidines. On the basis of these
      observations, Ni(2+) was chosen to probe the detection of a C-T mismatch in 15
      mer PNA-DNA films. Using Ni(2+), it is possible to detect a single C-T mismatch.
      The resulting DeltaR(CT) is larger for the PNA-DNA hybrid compared to that for
      the identical 15-mer DNA-DNA hybrid.

PMID- 20055459
TI  - Passive dosing to determine the speciation of hydrophobic organic chemicals in
      aqueous samples.
AB  - A new analytical approach to determine the speciation of hydrophobic organic
      analytes is presented. The freely dissolved concentration in a sample is
      controlled by passive dosing from silicone (poly(dimethylsiloxane)), and the
      total sample concentration at equilibrium is measured. The free fraction is
      determined as the ratio between measured concentrations in pure water and sample.
      (14)C-labeled fluoranthene served as model analyte, and total sample
      concentrations were easily measured by liquid scintillation counting. The method
      was applied to surface water, stormwater runoff, and wastewater. In the untreated
      wastewater, 61% of the fluoranthene was bound to suspended solids, 28% was
      associated to dissolved organic matter, and 11% was freely dissolved, while in
      treated wastewater, the speciation was 16% bound to suspended solids, 4% bound to
      dissolved organic matter, and 80% freely dissolved. The free fraction in roof
      runoff (85%) and surface water (91%) was markedly higher than in runoff from
      paved areas, which ranged from 27 to 36%. A log K(DOC) value of 5.26 was
      determined for Aldrich humic acid, which agrees well with reported values
      obtained by fluorescence quenching and solid phase microextraction (SPME). This
      analytical approach combines simplicity with high precision, and it does not
      require any phase separation steps.

PMID- 20055460
TI  - Indene-C(60) bisadduct: a new acceptor for high-performance polymer solar cells.
AB  - Polymer solar cells (PSCs) are commonly composed of a blend film of a conjugated
      polymer donor and a soluble C(60) derivative acceptor sandwiched between an ITO
      anode and a low-workfunction metal cathode. Poly(3-hexylthiophene) (P3HT) and
      [6,6]-phenyl-C-61-butyric acid methyl ester (PCBM) are the most widely used donor
      and acceptor materials, respectively. However, the low LUMO energy level of PCBM
      limits the open circuit voltage (V(oc)) of the P3HT-based PSCs to ca. 0.6 V. Here
      we synthesized a new soluble C(60) derivative, indene-C(60) bisadduct (ICBA),
      with a LUMO energy level 0.17 eV higher than that of PCBM. The PSC based on P3HT
      with ICBA as acceptor shows a higher V(oc) of 0.84 V and higher power conversion
      efficiency (PCE) of 5.44% under the illumination of AM1.5, 100 mW/cm(2), while
      the PSC based on P3HT/PCBM displays a V(oc) of 0.58 V and PCE of 3.88% under the
      same experimental conditions. The results indicate that ICBA is an alternative
      high-performance acceptor and could be widely used in high-performance PSCs.

PMID- 20055461
TI  - Triazacyclohexane (tach) complexes of high-valent rhenium: syntheses of
      [(R(3)tach)ReO(3)](+) (R = -CH(3), -CH(2)C(6)H(5)) and its substitution
      reactions.
AB  - N-Alkylated derivatives of 1,3,5-triazacyclohexane (tach) are versatile, facially
      coordinating ligands. We present the syntheses and full characterization of two
      new complexes of the [(R(3)tach)ReO(3)](+) type. In these complexes, the tach
      ligand is readily substituted by bi- and tridentate ligands; hence, they can be
      considered as sources of the [ReO(3)](+) motif for Re(VII) complexes.

PMID- 20055462
TI  - Micropollutant and sludge characterization for modeling sorption equilibria.
AB  - The sorption of hydrophobic micropollutants in sludge is one of the major
      mechanisms which drive their fate within wastewater treatment systems. The
      objective of this study was to investigate the influence of both sludge and
      micropollutant characteristics on the equilibria of sorption to particles and to
      dissolved and colloidal matter (DCM). For this purpose, the equilibrium constants
      were measured for 13 polycyclic aromatic hydrocarbons, 5 polychlorobiphenyls and
      the nonylphenol, and five different sludge types encountered in treatment
      systems: a primary sludge, a secondary sludge, the same secondary sludge after
      thermal treatment, after anaerobic digestion, and after both treatments. After
      thermal treatment, no more sorption to DCM was observed. Anaerobic biological
      treatment was shown to enhance micropollutants sorption to particles and to DCM
      of one logarithmic unit, due to matter transformation. Partial least-squares
      linear regressions of sorption data as a function of micropollutant and sludge
      properties revealed that sludge physical and chemical characteristics were more
      influential than micropollutant characteristics. Two models were provided to
      predict the sorption of such micropollutants in any sludge. To our knowledge,
      this is the first time that a three-compartment approach is used to accurately
      model micropollutant sorption in sludge and to understand the driving mechanisms.

PMID- 20055463
TI  - The two enantiomers of citalopram bind to the human serotonin transporter in
      reversed orientations.
AB  - The two enantiomers of the antidepressant citalopram inhibit the human serotonin
      transporter substantially differently. Previous studies revealed Tyr95 and Ile172
      as important for citalopram binding, however, the overall orientation of the
      ligands in the binding site and the protein-ligand interaction points remain
      unknown. The binding of S- and R-citalopram to a human serotonin transporter
      homology model are herein examined via docking simulations including induced fit
      effects. For a better description of the formal charges of the ligand when bound
      inside the protein, polarization effects of the protein were included by
      additional quantum-polarized ligand docking calculations, where ligand charges
      are evaluated using QM/MM calculations. By this approach a much clearer picture
      emerged of the positions of the functional groups of citalopram. The two
      enantiomers are predicted to bind in the substrate binding pocket with opposite
      orientations of their aromatic groups. The predicted binding modes are
      experimentally validated using human wild type and 15 serotonin transporter
      mutants and 13 optically pure citalopram analogues. Important protein-ligand
      interaction points were identified validating one binding model for each
      enantiomer. In the validated model of the high affinity enantiomer, S-citalopram,
      the fluorine atom is located near Ala173 and Thr439 and the cyano group is in
      close proximity of Phe341; these contacts are found to be reversed for the R
      enantiomer.

PMID- 20055464
TI  - 2D assembly of metallacycles on HOPG by shape-persistent macrocycle templates.
AB  - The synthesis and scanning tunneling microscopy (STM) investigations of shape
      persistent arylene-ethynylene-butadiynylene macrocycles along with their
      codeposites with metallacycles are reported. 2D ordered arrays of macrocycles and
      macrocycle/metallacycle architectures (1:1) have been obtained on HOPG by self
      assembly under ambient conditions. It is found that the ordered macrocycle array
      acts as a template for the deposition of the adlayer molecules. For each
      underlying macrocycle, one metallacycle has been detected. The unit-cell data of
      both, the macrocycles and their codeposites, show that the structural information
      of the macrocycle layer is perfectly transformed to the guest molecules. A rather
      unexpected observation is that the present compound could not be coadsorbed with
      C(60), indicating that only a minor change in the structure of the macrocycle has
      a dramatic effect on the ability of the monolayer to bind additional guest
      molecules.

PMID- 20055465
TI  - Coalescence control of elastomer clusters by fixed surface charges.
AB  - We studied the coalescence behavior of a fluorinated elastomer colloid,
      stabilized by fixed surface charges, with a glass transition temperature of about
      -20 degrees C, as a function of temperature under diffusion-limited cluster
      cluster aggregation (DLCA) conditions. We first measured the aggregation kinetics
      by in situ dynamic light scattering and then simulated it through the
      Smoluchowski approach (i.e., population balance equations) using the only unknown
      parameter, the fractal dimension D(f) of the clusters, as the fit parameter. It
      was found that the estimated D(f) value increased as the temperature increased,
      starting from 1.7 at 25 degrees C and reaching the upper limit of 3.0 for T > or
      = 55 degrees C. These results indicate that the coalescence extent increases as
      the temperature increases. Such temperature-dependent coalescence behavior cannot
      be explained by thermodynamic considerations, and it must be related to a certain
      kinetic resistance. We explain this effect by considering the resistance of the
      fixed charges to relocation on the particle surface, which decreases as the
      temperature increases.

PMID- 20055467
TI  - Novel intramolecular energy transfer probe for the detection of benzo[a]pyrene
      metabolites in a homogeneous competitive fluorescence immunoassay.
AB  - The spectroscopic properties of a novel intramolecular energy transfer probe (ET
      probe)--consisting of 3-hydroxybenzo[a]pyrene (3OH-BaP) as the donor covalently
      linked to sulforhodamine B (SRB) as the acceptor--for the detection of polycyclic
      aromatic hydrocarbons (PAH) antibody binding were characterized. Absorption and
      fluorescence spectra as well as fluorescence decay curves were recorded in
      methanol and aqueous solution, respectively. For comparison, the parent
      chromophores 3OH-BaP and SRB were investigated as well. In the case of the ET
      probe, a very strong fluorescence quenching of the BaP-moiety-related emission
      due to an efficient energy transfer (energy transfer efficiency of about 0.95 for
      methanol) to the SRB moiety was observed. Upon addition of the PAH antibody, the
      fluorescence intensity and anisotropy of the BaP moiety was drastically
      increased. On the other hand, the fluorescence anisotropy of the SRB moiety did
      not change. The anisotropy results clearly indicate the binding of the antibody.
      On the basis of these findings, we concluded the following model: the BaP moiety
      is incorporated in the antibody binding site, whereas the SRB moiety sticks out
      from the binding site, restricting the motion of the BaP moiety, but leaving the
      SRB moiety uninfluenced. More important, this structure results in a disruption
      of the intramolecular energy transfer. The antibody-induced disruption of the
      intramolecular energy transfer is envisaged as a detection scheme in a future
      homogeneous competitive fluorescence immunoassay (FIA). This may provide a novel
      general detection principle for the immunodetection of low-molecular analytes
      (haptens) in a homogeneous competitive FIA format.

PMID- 20055466
TI  - Multifrequency EPR studies of manganese catalases provide a complete description
      of proteinaceous nitrogen coordination.
AB  - Pulse electron paramagnetic resonance (EPR) spectroscopy is employed at two very
      different excitation frequencies, 9.77 and 30.67 GHz, in the study of the
      nitrogen coordination environment of the Mn(III)Mn(IV) state of the dimanganese
      containing catalases from Lactobacillus plantarum and Thermus thermophilus.
      Consistent with previous studies, the lower-frequency results reveal one unique
      histidine nitrogen-Mn cluster interaction. For the first time, a second, more
      strongly hyperfine-coupled (14)N atom is unambiguously observed through the use
      of higher frequency/higher field EPR spectroscopy. The low excitation frequency
      spectral features are rationalized as arising from the interaction of a histidine
      nitrogen that is bound to the Mn(IV) ion, and the higher excitation frequency
      features are attributed to the histidine nitrogen bound to the Mn(III) ion. These
      results allow for the computation of intrinsic hyperfine coupling constants,
      which range from 2.2 to 2.9 MHz, for sp(2)-hybridized nitrogens coordinating
      equatorially to high-valence Mn ions. The relevance of these findings is
      discussed in the context of recent results from analogous higher frequency EPR
      studies of the Mn cluster in photosystem II and other exchange-coupled,
      transition metal-containing systems.

PMID- 20055468
TI  - Inclusion complexes of nitroxides of pyrrolidine and imidazoline series with
      cucurbit[7]uril.
AB  - Inclusion of nitroxides into the cavity of molecular nanocontainers may prevent
      or significantly retard nitroxide reactions with cellular reductans and increase
      nitroxide lifetime. This paper is aimed at studying possible applications of
      cucurbit[7]uril (CB7) as a molecular nanocontainer for pH-sensitive nitroxides
      probes. Inclusion complexes of CB7 with different nitroxides--3-aminomethyl
      proxyl (AMP), 3-hydroxymethyl-proxyl (HMP), 4-amino-2,2,5,5-tetramethyl-2,5
      dihydroimidazole-1-oxyl (ATI), and 2,2,4,5,5-pentamethyl-2,5-dihydroimidazole-1
      oxyl (MTI)--were studied. It was found that reversible formation of inclusion
      complexes AMP@CB7, AMPH(+)@CB7, HMP@CB7, ATIH(+)@CB7, and MTIH(+)@CB7 is
      accompanied by a decrease of hyperfine interaction (HFI) constant on nitrogen of
      the nitroxide group and by a 5-7-fold increase of rotational correlation time
      monitored by electron paramagnetic resonance (EPR). The binding constants of
      nitroxide@CB7 complexes were determined, and the influence of alkali metal ions
      and pH on the equilibrium between free and encapsulated nitroxides was studied.
      The EPR spectra of CB7 mixtures with protonable nitroxides were found to be more
      sensitive to pH changes than the spectra of pure nitroxides, and the apparent pK
      of these mixtures was found to increase with CB7 concentration. The nitroxide@CB7
      complexes showed higher resistance to chemical reduction with ascorbic acid
      compared to free nitroxides. Thus, CB7 can be used for the improvement of
      functional properties of nitroxides.

PMID- 20055469
TI  - Effect of salt content on the rheological properties of hydrogel based on
      oligomeric electrolyte.
AB  - Dynamic light scattering and oscillatory rheology experiments were performed to
      study the effects of various salts on the hydrogel consisting of an oligomeric
      electrolyte gelator, poly(pyridinium-1,4-diyliminocarbonyl-1,4-phenylenemethylene
      chloride) (1-Cl). Sol-gel transition temperature increased with increasing salt
      concentration that suggested the salt-in behavior. The concentration dependence
      of the dynamic shear moduli showed power-law scaling behavior and was compared
      with the predictions made by the fractal gel model. The brittleness was increased
      by increasing salt concentration, indicating that 1-Cl hydrogel became better
      packed into stronger networks in ionic solutions. After certain salt
      concentrations, 1-Cl hydrogel started precipitation that might be due to the
      excessive network formation resulting in collapse of the network structure. The
      recovery of the mechanical properties of 1-Cl hydrogel was completely reduced in
      the presence of salts.

PMID- 20055470
TI  - Synthesis and characterization of 6,6'-(2,4,6-triisopropylphenyl)-2,2'-bipyridine
      (tripbipy) and its complexes of the late first row transition metals.
AB  - The synthesis of tripbipy, a new substituted bipyridine ligand (6,6'-(2,4,6
      triisopropylphenyl)-2,2'-bipyridine), and the syntheses, structures, and magnetic
      properties of the first coordination compounds based on this ligand are
      described. Tripbipy was synthesized by the Suzuki coupling of 2,4,6
      triisopropylphenyl boronic acid and 6,6'-dibromo-2,2'-bipyridine. Reported here
      are the tripbipy complexes of five late first row transition metal chlorides
      (MCl(2); M = Fe, Co, Ni, Cu, Zn). Four of the complexes MCl(2)tripbipy (M = Fe,
      Co, Ni, Zn) crystallize in the space group P2(1)/c and are isomorphous with one
      solvent molecule of crystallization. The complex CuCl(2)tripbipy crystallizes in
      the space group P2(1)2(1)2(1) with two solvent molecules of crystallization. All
      MCl(2)tripbipy complexes are four coordinate and contain distorted tetrahedral
      metal centers. CuCl(2)tripbipy shows a pseudo Jahn-Teller distortion, and X-band
      electron paramagnetic resonance (EPR) in a toluene glass gives approximate g(
      perpendicular, parallel) values of 2.2 and 2.1. Magnetic measurements (M = Fe,
      Co, Ni, Cu) are consistent with high spin d(n) configurations (n = 6-9, S = 2,
      3/2, 1, 1/2) tetrahedral complexes and give chi(M)T values at 300 K of 3.56,
      2.10, 1.01, and 0.37 cm(3) M(-1) K, respectively.

PMID- 20055471
TI  - Density functional analysis of the trigonal uranyl equatorial coordination in
      hexahomotrioxacalix[3]arene-based macrocyclic complexes.
AB  - Representative models of the different geometries observed for uranyl complexes
      with fully deprotonated p-R-hexahomotrioxacalix[3]arene (R = tert-Bu, Me)
      ligands, among which is the rare trigonal geometry, have been investigated using
      all-electron scalar relativistic density functional theory (DFT). Optimized
      structures of complexes incorporating triethylammonium (HNEt3+) and 4
      methylpiperidinium (HMePi+) cations are in close agreement with experimental
      crystal diffraction data. Possible explanations for the structural differences
      between these uranyl complexes are discussed in terms of varying degrees of
      bonding between uranium and oxygen atoms from the ether and phenoxide groups. In
      particular, molecular orbital analysis highlights the central role of 5f-2p
      hybridization in the U-O bonding.

PMID- 20055472
TI  - Do spiroarsoranes exhibit polytopal equilibrium in solution?
AB  - The spiroarsoranes 5-phenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane
      (6), (3R,8R)-3,8-dimethyl-5-phenyl-1,6-dioxa-4,9-diaza-5lambda(5)
      arsaspiro[4.4]nonane (7), (2S,7S)-2,7-dimethyl-5-phenyl-1,6-dioxa-4,9-diaza
      5lambda(5)-arsaspiro[4.4]nonane (8), and (3S,8S)-3,8-dimethyl-(2R,7R)-2,5,7
      triphenyl-1,6-dioxa-4,9-diaza-5lambda(5)-arsaspiro[4.4]nonane (9) were prepared
      by reaction of phenylarsonic acid and the correspondig amino alcohol. The
      presence of polytopal Delta left arrow over right arrow Lambda equilibrium in 6-9
      was demonstrated by HPLC and NMR studies. NBO computations at the MP2/6
      31+G(2d,2p) level indicate that methyl substitution in C2 or C3 of the
      oxazarsolane ring determines the predominance of Delta or Lambda stereoisomers.
      GIAO B3LYP/6-311++G(2d,2p) computations were used to assign experimental (1)H and
      (13)C NMR spectra.

PMID- 20055473
TI  - Versatile new bis(thiosemicarbazone) bifunctional chelators: synthesis,
      conjugation to bombesin(7-14)-NH(2), and copper-64 radiolabeling.
AB  - New bifunctional derivatives of diacetyl-bis(4-methylthiosemicarbazone)
      (H(2)atsm) have been prepared by a selective transamination reaction of a new
      dissymmetric bis(thiosemicarbazone) precursor H(2)L(1). The new derivatives
      contain an aliphatic carboxylic acid (H(2)L(2) and H(2)L(3)), t-butyl carbamate
      (H(2)L(4)), or ammonium ion (H(2)L(5)) functional group. The new ligands and
      copper(II) complexes have been characterized by NMR spectroscopy, mass
      spectrometry, and microanalysis. The complex Cu(II)(L(4)) was structurally
      characterized by X-ray crystallography and shows the metal center to be in an
      N(2)S(2) distorted square planar coordination geometry. Electrochemical
      measurements show that the copper(II) complexes undergo a reversible reduction
      attributable to a Cu(II)/Cu(I) process. The ligands and the copper(II) complexes
      featuring a carboxylic acid functional group have been conjugated to the tumor
      targeting peptide bombesin(7-14)-NH(2). The bifunctional peptide conjugates were
      radiolabeled with copper-64 in the interest of developing new positron emission
      tomography (PET) imaging agents. The conjugates were radiolabeled with copper-64
      rapidly in high radiochemical purity (>95%) at room temperature under mild
      conditions and were stable in a cysteine and histidine challenge study.

PMID- 20055474
TI  - Molecular mechanisms underlying the early stage of protein translocation through
      the Sec translocon.
AB  - The Sec translocon, a protein-conducting channel, consists of a heterotrimeric
      complex (SecYEG in bacteria and Sec61 alpha beta gamma in eukaryotes) that
      provides a pathway for secretary proteins to cross membranes, or for membrane
      proteins to integrate into the membrane. The Sec translocon alone is a passive
      channel, and association with channel partners, including the ribosome or SecA
      ATPase in bacteria, is needed for protein translocation. Three recently published
      crystal structures of SecY are considered to represent the closed (resting
      state), pre-open (transitional state determined with the bound Fab fragment
      mimicking SecA interaction), and SecA-bound forms. To elucidate mechanisms of
      transition between closed and pre-open forms, we performed all-atom molecular
      dynamics simulations for the pre-open form of Thermus thermophilus SecYE and the
      closed form of Methanococcus janaschii SecYE beta in explicit solvent and
      membranes. We found that the closed form of SecY is stable, while the pre-open
      form without the Fab fragment undergoes large conformational changes toward the
      closed form. The pre-open form of SecY with Fab remains unchanged, suggesting
      that the cytosolic interaction mimicking SecA binding stabilizes the pre-open
      form of SecY. Importantly, a lipid molecule at the lateral gate region appears to
      be required to maintain the pre-open form in the membrane. We propose that the
      conformational transition from closed to pre-open states of SecY upon association
      with SecA facilitates intercalation of phospholipids at the lateral gate,
      inducing initial entry of the positively charged signal peptide into the channel.

PMID- 20055475
TI  - Controlled positioning of carbon nanotubes by dielectrophoresis: insights into
      the solvent and substrate role.
AB  - We demonstrate the ability to precisely control the deposition of a defined
      number of carbon nanotubes (CNTs) from solution onto microfabricated electrodes
      using dielectrophoresis. The solvation shell around the CNTs, exhibiting a high
      dielectric constant which is possibly larger than the intrinsic dielectric
      constant of CNTs, is found to play a crucial role in electrophoretic processes.
      Substrate resistivity is also very important: The spatial repartition of the
      electric field between the substrate and the microelectrodes leads to deviations
      from the precise location of the CNTs. A recipe is given for the
      dielectrophoresis of CNTs which can be extended to other nanowires or nanotubes.

PMID- 20055476
TI  - Site-specific deposition of Au nanoparticles in CNT films by chemical bonding.
AB  - There has been no attempt to date to specifically modify the nodes in carbon
      nanotube (CNT) networks. If the nodes can be modified in favorable ways, the
      electrical and/or thermal and/or mechanical properties of the CNT networks could
      be improved. In an attempt to influence the performance as a transparent
      conductive film, gold nanoparticles capped with the amino acid cysteine (Au
      CysNP) have been selectively attached at the nodes of multiwalled carbon
      nanotubes (MWCNTs) networks. These nanoparticles have an average diameter of 5 nm
      as observed by TEM. FTIR and XPS were used to characterize each step of the MWCNT
      chemical functionalization process. The chemical process was designed to favor
      selective attachment at the nodes and not the segments in the CNT networks. The
      chemical processing was designed to direct formation of nodes where the gold
      nanoparticles are. The nanoparticles which were loosely held in the CNT network
      could be easily washed away by solvents, while those bound chemically remained.
      TEM results show that the Cys-AuNPs are preferentially located at the nodes of
      the CNT networks when compared to the segments. These nanoparticles at the nodes
      were also characterized by a novel technique called diffraction scanning
      transmission electron microscopy (D-STEM) confirming their identity. Four-probe
      measurements found that the sheet resistance of the modified CNT networks was
      half that of similarly transparent pristine multiwalled CNT networks.

PMID- 20055477
TI  - Pycnanthulignenes A-D, antimicrobial cyclolignene derivatives from the roots of
      Pycnanthus angolensis.
AB  - Investigation of the constituents of Pycnanthus angolensis roots has resulted in
      the isolation of four new cyclolignene derivatives, named pycnanthulignene A (1),
      pycnanthulignene B (2), pycnanthulignene C (3), and pycnanthulignene D (4), and
      six known compounds, 4,5-dimethoxy-3',4'-methylenedioxy-2,7'-cycloligna-7,7'
      diene, 2,7-dimethoxy-3,6-dimethylnaphthalene, 4'-methoxy-4,5-methylenedioxy-2,7'
      cyclolign-7-ene, genkwainin, 8-hydroxykanzakiflavone-2, and formononetin. The
      structures of these compounds were established using spectroscopic methods.
      Compounds 1 and 3 showed significant antimicrobial activities against a panel of
      drug-resistant pathogens.

PMID- 20055478
TI  - Novel peptoid building blocks: synthesis of functionalized aromatic helix
      inducing submonomers.
AB  - Peptoids, oligo-N-substituted glycines, can fold into well-defined helical
      secondary structures. The design and synthesis of new peptoid building blocks
      that are capable of both (a) inducing a helical secondary structure and (b)
      decorating the helices with chemical functionalities are reported. Peptoid
      heptamers containing carboxamide, carboxylic acid or thiol functionalities were
      synthesized, and the resulting peptoids were shown to form stable helices. A
      thiol-containing peptoid readily formed the homodisulfide, providing a convenient
      route to prepare peptoid helix homodimers.

PMID- 20055479
TI  - Radiative heat pumping from the Earth using surface phonon resonant
      nanoparticles.
AB  - Nanoparticles that have narrow absorption bands that lie entirely within the
      atmosphere's transparent window from 7.9 to 13 mum can be used to radiatively
      cool to temperatures that are well below ambient. Heating from incoming
      atmospheric radiation in the remainder of the Planck radiation spectrum, where
      the atmosphere is nearly "black", is reduced if the particles are dopants in
      infrared transmitting polymers, or in transmitting coatings on low emittance
      substrates. Crystalline SiC nanoparticles stand out with a surface phonon
      resonance from 10.5 to 13 mum clear of the atmospheric ozone band. Resonant
      SiO(2) nanoparticles are complementary, absorbing from 8 to 10 mum, which
      includes atmospheric ozone emissions. Their spectral location has made SiC
      nanoparticles in space dust a feature in ground-based IR astronomy. Optical
      properties are presented and subambient cooling performance analyzed for doped
      polyethylene on aluminum. A mixture of SiC and SiO(2) nanoparticles yields high
      performance cooling at low cost within a practical cooling rig.

PMID- 20055480
TI  - Visualizing the optical interaction tensor of a gold nanoparticle pair.
AB  - The control of optical fields on the nanometer scale is a central theme of
      plasmonics and nanophotonics. Methods for characterizing localized optical field
      distributions are necessary to validate theoretical predictions, to test
      nanofabrication procedures, and to provide feedback for design improvements.
      Typical methods of probing near fields (e.g., single molecule fluorescence and
      near-field microscopy) cannot probe both the complex-valued and vectorial nature
      of the field distributions. We demonstrate that a nanoparticle probe with
      isotropic polarizability in combination with polarization control of excitation
      and detection beams provides access to this information through the interaction
      tensor. For a sample consisting of a single nanoparticle we show that the
      recorded images correspond to maps of the local Green's function tensor elements
      that couple the probe and sample. The tensorial mapping of interacting
      nanoparticles is of interest for optical sensing, optical antennas, surface
      enhanced Raman scattering, nonlinear optics, and molecular rulers.

PMID- 20055481
TI  - Ricin activity assay by direct analysis in real time mass spectrometry detection
      of adenine release.
AB  - Biotoxin activity assays typically involve multistep sample preparation,
      multicomponent reactions, multistep analysis, or a combination thereof. We report
      a single-step, real-time ricin activity assay that requires little or no sample
      preparation and employs direct analysis in real time mass spectrometry. The
      release of adenine from the inhomogeneous substrate herring sperm DNA by ricin
      was determined to be 53 +/- 2 pmol adenine per picomole of ricin per hour. This
      procedure can be readily adapted to any enzyme for which a reactant or product of
      low molecular weight (up to approximately 600) can be identified.

PMID- 20055483
TI  - 6,8-Di-C-glycosyl flavonoids from Dendrobium huoshanense.
AB  - Dendrobium huoshanense is a valued herbal plant used in traditional Chinese
      medicine. Fractionation of the water-soluble part of D. huoshanense by repeated
      chromatography culminated in the isolation of four new 6,8-di-C-glycosyl flavones
      (1-4), in addition to seven known compounds, comprising malic acid, dimethyl
      malate, N-phenylacetamide, isopentyl butyrate, salicylic acid, shikimic acid, and
      isoschaftoside. By detailed spectroscopic analysis, the structures of 1-4 were
      determined to have a core of apigenin bearing pentoside (arabinoside or xyloside)
      and rhamnosyl-hexoside (glucoside or galactoside) substituents.

PMID- 20055484
TI  - Role of surfactants in carbon nanotubes density gradient separation.
AB  - Several strategies aimed at sorting single-walled carbon nanotubes (SWNT) by
      diameter and/or electronic structure have been developed in recent years. A
      nondestructive sorting method was recently proposed in which nanotube bundles are
      dispersed in water-surfactant solutions and submitted to ultracentrifugation in a
      density gradient. By this method, SWNTs of different diameters are distributed
      according to their densities along the centrifuge tube. A mixture of two anionic
      amphiphiles, namely sodium dodecylsulfate (SDS) and sodium cholate (SC),
      presented the best performance in discriminating nanotubes by diameter. We
      present molecular dynamics studies of the water-surfactant-SWNT system. The
      simulations revealed one aspect of the discriminating power of surfactants: they
      can actually be attracted toward the interior of the nanotube cage. The binding
      energies of SDS and SC on the outer nanotube surface are very similar and depend
      weakly on diameter. The binding inside the tubes, on the contrary, is strongly
      diameter dependent: SDS fits best inside tubes with diameters ranging from 8 to 9
      A, while SC is best accommodated in larger tubes, with diameters in the range
      10.5-12 A. The dynamics at room temperature showed that, as the amphiphile moves
      to the hollow cage, water molecules are dragged together, thereby promoting the
      nanotube filling. The resulting densities of filled SWNT are in agreement with
      measured densities.

PMID- 20055482
TI  - Mechanism and inhibition of the FabV enoyl-ACP reductase from Burkholderia
      mallei.
AB  - Enoyl-ACP reductases catalyze the final step in the elongation cycle of the
      bacterial fatty acid biosynthesis (FAS-II) pathway. At present, four distinct
      enoyl-ACP reductases have been identified, which are the products of the fabI,
      fabL, fabK, and fabV genes. The FabV enoyl-ACP reductase is the most recent
      member of this enzyme class and was originally identified in Vibrio cholerae by
      Cronan and co-workers [Massengo-Tiasse, R. P., and Cronan, J. E. (2008) Vibrio
      cholerae FabV defines a new class of enoyl-acyl carrier protein reductase. J.
      Biol. Chem. 283, 1308-1316]. In this work, a detailed kinetic analysis of the
      mechanism of the FabV enzyme from Burkholderia mallei (bmFabV) has been
      undertaken, which reveals that bmFabV catalyzes a sequential bi-bi mechanism with
      NADH binding first and NAD(+) dissociating last. The enzyme is a member of the
      short chain dehydrogenase/reductase superfamily in which the catalytic tyrosine
      (Y235) and lysine (K244) residues are organized in the consensus Tyr-(Xaa)(8)-Lys
      motif. The role of these active site residues has been investigated using site
      directed mutagenesis which has shown that both Y235 and K244 are involved in acid
      base chemistry during substrate reduction. Sequence alignment and site-directed
      mutagenesis also identify a second lysine in the active site (K245) that has an
      important role in binding of the enoyl substrate. Because of interests in
      developing inhibitors of bmFabV, a detailed analysis of the inhibition of the
      enzyme by triclosan has been conducted showing that triclosan is a competitive
      inhibitor with respect to NADH and an uncompetitive inhibitor with respect to the
      substrate 2-dodecenoyl-CoA (K(i) = 0.4 muM). In combination with fluorescence
      binding experiments, we conclude that triclosan binds to the enzyme-NAD(+)
      product complex which is in rapid and reversible equilibrium with other
      intermediates on the reaction pathway.

PMID- 20055485
TI  - Planar chromatography.

PMID- 20055486
TI  - Federal land management, carbon sequestration, and climate change in the
      Southeastern U.S.: a case study with Fort Benning.
AB  - Land use activities can have a major impact on the temporal trends and spatial
      patterns of regional land-atmosphere exchange of carbon. Federal lands generally
      have substantially different land management strategies from surrounding areas,
      and the carbon consequences have rarely been quantified and assessed. Using the
      Fort Benning Installation as a case study, we used the General Ensemble
      biogeochemical Modeling System (GEMS) to simulate and compare ecosystem carbon
      sequestration between the U.S. Army's Fort Benning and surrounding areas from
      1992 to 2050. Our results indicate that the military installation sequestered
      more carbon than surrounding areas from 1992 to 2007 (76.7 vs 18.5 g C m(-2) yr(
      1)), and is projected to continue sequestering more carbon from 2008 to 2050
      (75.7 vs 25.6 g C m(-2) yr(-1)), mostly because of the proactive management
      approaches adopted on military training lands. Our results suggest that federal
      lands might play a positive and important role in sequestering and conserving
      atmospheric carbon because some anthropogenic disturbances (e.g., urbanization,
      forest harvesting, and agriculture) can be minimized or prevented on federal
      lands.

PMID- 20055487
TI  - Chemical lake restoration products: sediment stability and phosphorus dynamics.
AB  - Laboratory experiments with sediments from three shallow Danish lakes were
      conducted to evaluate the effects of chemical lake restoration products during
      resuspension. Phosphorus (P) removal, sediment stability, sediment consolidation
      and color reduction were studied over time. The investigated products were
      aluminum (Al), Phoslock (a commercial bentonite product coated with lanthanum)
      and a combination of Al covered with bentonite (Al/Ben). All treatments
      effectively reduced the P concentration in the water. However, the treatments
      containing Al reduced the P concentration immediately after resuspension, whereas
      Phoslock required several days after resuspension to reduce the P concentration.
      Especially Phoslock, but also Al/Ben, increased the sediment stability threshold
      by 265% and 101%, respectively, whereas Al had no stabilizing effect. The fresh
      Al floc was resuspended 5x easier than untreated sediment. The largest
      consolidation of the sediment occurred with addition of Phoslock, followed by
      Al/Ben, while Al alone had no effect. Enhanced consolidation may be of importance
      for macrophyte colonisation of organic sediment. Phoslock improved the light
      climate moderately by removing color, whereas Al was very effective in removing
      color. Ben/Al showed intermediate effects on color reduction. These findings are
      important when decisions are made on restoration method for a specific lake,
      which may be more or less wind exposed.

PMID- 20055488
TI  - Resistance switching in electrodeposited magnetite superlattices.
AB  - Defect-chemistry magnetite superlattices and compositional superlattices in the
      magnetite/zinc ferrite system are electrodeposited as epitaxial films onto single
      crystal Au(111). The defect-chemistry superlattices have alternating nanolayers
      with different Fe(III)/Fe(II) ratios, whereas the compositional superlattices
      have alternating nanolayers with different Zn/Fe ratios. The
      electrochemical/chemical (EC) nature of the electrodeposition reaction is
      exploited to deposit the superlattices by pulsing the applied potential during
      deposition. The defect-chemistry superlattices show low-to-high and high-to-low
      resistance switching that may be applicable to the fabrication of resistive
      random access memory (RRAM).

PMID- 20055489
TI  - Novel application of 2D and 3D-similarity searches to identify substrates among
      cytochrome P450 2C9, 2D6, and 3A4.
AB  - Cytochrome P450 (CYP450) is a class of enzymes where the substrate identification
      is particularly important to know. It would help medicinal chemists to design
      drugs with lower side effects due to drug-drug interactions and to extensive
      genetic polymorphism. Herein, we discuss the application of the 2D and 3D
      similarity searches in identifying reference structures with higher capacity to
      retrieve substrates of three important CYP enzymes (CYP2C9, CYP2D6, and CYP3A4).
      On the basis of the complementarities of multiple reference structures selected
      by different similarity search methods, we proposed the fusion of their
      individual Tanimoto scores into a consensus Tanimoto score (T(consensus)). Using
      this new score, true positive rates of 63% (CYP2C9) and 81% (CYP2D6) were
      achieved with false positive rates of 4% for the CYP2C9-CYP2D6 data set. Extended
      similarity searches were carried out on a validation data set, and the results
      showed that by using the T(consensus) score, not only the area of a ROC graph
      increased, but also more substrates were recovered at the beginning of a ranked
      list.

PMID- 20055490
TI  - Electrochemical detection in a paper-based separation device.
AB  - Prototypes of microfluidic paper-based separation devices with amperometric
      detection were developed and evaluated. Photolithography was used to make a gold
      electrochemical microcell on polyester and that microcell was coupled to a strip
      of paper where a chromatographic separation occurs. The device performance was
      demonstrated with the separation and quantification of uric and ascorbic acid in
      mixtures. The method provides an analytical alternative for the determination of
      compounds where low cost and simplicity are essential.

PMID- 20055491
TI  - Functional characterization of the cyclomarin/cyclomarazine prenyltransferase
      CymD directs the biosynthesis of unnatural cyclic peptides.
AB  - In vitro and in vivo characterization of the cyclomarin/cyclomarazine
      prenyltransferase CymD revealed its ability to prenylate tryptophan prior to
      incorporation into both cyclic peptides by the nonribosomal peptide synthetase
      CymA. This knowledge was utilized to bioengineer novel derivatives of these
      marine bacterial natural products by providing synthetic N-alkyl tryptophans to a
      prenyltransferase-deficient mutant of Salinispora arenicola CNS-205.

PMID- 20055492
TI  - Investigations of interhydrogen bond dynamical coupling effects in the polarized
      IR spectra of acetanilide crystals.
AB  - This Article presents the investigation results of the polarized IR spectra of
      the hydrogen bond in acetanilide (ACN) crystals measured in the frequency range
      of the proton and deuteron stretching vibration bands, nu(N-H) and nu(N-D). The
      basic spectral properties of the crystals were interpreted quantitatively in
      terms of the "strong-coupling" theory. The model of the centrosymmetric dimer of
      hydrogen bonds postulated by us facilitated the explanation of the well
      developed, two-branch structure of the nu(N-H) and nu(N-D) bands as well as the
      isotopic dilution effects in the spectra. On the basis of the linear dichroic and
      temperature effects in the polarized IR spectra of ACN crystals, the H/D isotopic
      "self-organization" effects were revealed. A nonrandom distribution of hydrogen
      isotope atoms (H or D) in the lattice was deduced from the spectra of
      isotopically diluted ACN crystals. It was also determined that identical hydrogen
      isotope atoms occupy both hydrogen bonds in the dimeric systems, where each
      hydrogen bond belongs to a different chain. A more complex fine structure pattern
      of nu(N-H) and nu(N-D) bands in ACN spectra in comparison with the spectra of
      other secondary amides (e.g., N-methylacetamide) can be explained in terms of the
      "relaxation" theory of the IR spectra of hydrogen-bonded systems.

PMID- 20055493
TI  - Thermal stability of precursors for atomic layer deposition of TiO2, ZrO2, and
      HfO2: an ab initio study of alpha-hydrogen abstraction in bis-cyclopentadienyl
      dimethyl complexes.
AB  - Thin film dielectrics based on hafnium and zirconium oxides are being introduced
      to increase the permittivity of insulating layers in nanoelectronic transistor
      and memory devices. Atomic layer deposition (ALD) is the process of choice for
      fabricating these films, and the success of this method depends crucially on the
      chemical properties of the precursor molecules. Designing new precursors requires
      molecular engineering and chemical tailoring to obtain specific physical
      properties and performance capabilities. A successful ALD precursor should be
      volatile, stable in the gas-phase, but reactive on the substrate and growing
      surface, leading to inert byproduct. This study is concerned with the thermal
      stability in the gas phase of Ti, Zr, and Hf precursors that contain
      cyclopentadienyl (Cp = C(5)H(5-x)R(x)) ligands. We use density functional theory
      (DFT) to probe the non-ALD decomposition pathway and find a mechanism via
      intramolecular alpha-H transfer that produces an alkylidene complex. The analysis
      shows that thermal stabilities of complexes of the type MCp(2)(CH(3))(2) increase
      down group 4 (M = Ti, Zr, and Hf) due to an increase in the HOMO-LUMO band gap of
      the reactants, which itself increases with the electrophilicity of the metal.
      Precursor decomposition via this pathway in the gas phase can therefore be
      avoided by replacing the alpha-H donor or acceptor ligands or by increasing the
      electrophilicity of the metal. This illustrates how the ALD process window can be
      widened by rational molecular design based on mechanistic understanding.

PMID- 20055494
TI  - Antimicrobial susceptibility testing using high surface-to-volume ratio
      microchannels.
AB  - This study reports the use of microfluidics, which intrinsically has a large
      surface-to-volume ratio, toward rapid antimicrobial susceptibility testing at the
      point of care. By observing the growth of uropathogenic Escherichia coli in gas
      permeable polymeric microchannels with different dimensions, we demonstrate that
      the large surface-to-volume ratio of microfluidic systems facilitates rapid
      growth of bacteria. For microchannels with 250 microm or less in depth, the
      effective oxygenation can sustain the growth of E. coli to over 10(9) cfu/mL
      without external agitation or oxygenation, which eliminates the requirement of
      bulky instrumentation and facilitates rapid bacterial growth for antimicrobial
      susceptibility testing at the point of care. The applicability of microfluidic
      rapid antimicrobial susceptibility testing is demonstrated in culture media and
      in urine with clinical bacterial isolates that have different antimicrobial
      resistance profiles. The antimicrobial resistance pattern can be determined as
      rapidly as 2 h compared to days in standard clinical procedures facilitating
      diagnostics at the point of care.

PMID- 20055495
TI  - Discorhabdins from the Korean marine sponge Sceptrella sp.
AB  - Two new pyrroloiminoquinone alkaloids of the discorhabdin class, along with 12
      compounds including one previously described synthetic derivative of the same and
      related skeletal classes, were isolated from the sponge Sceptrella sp., collected
      from Gageodo, Korea. The structures of these new compounds, designated as (-)-3
      dihydrodiscorhabdin D (11) and (-)-discorhabdin Z (12), were determined by
      combined spectroscopic analyses. Compound 12 possesses an unusual hemiaminal
      group among the discorhabdin alkaloids. These compounds exhibited moderate to
      significant cytotoxicity, antibacterial activity, and inhibitory activity against
      sortase A.

PMID- 20055496
TI  - Molecular mechanisms of system control of NF-kappaB signaling by IkappaBalpha.
AB  - The NF-kappaB family of transcription factors responds to inflammatory cytokines
      with rapid transcriptional activation and subsequent signal repression. Much of
      the system control depends on the unique characteristics of its major inhibitor,
      IkappaBalpha, which appears to have folding dynamics that underlie the
      biophysical properties of its activity. Theoretical folding studies followed by
      experiments have shown that a portion of the ankyrin repeat domain of
      IkappaBalpha folds on binding. In resting cells, IkappaBalpha is constantly being
      synthesized, but most of it is rapidly degraded, leaving only a very small pool
      of free IkappaBalpha. Nearly all of the NF-kappaB is bound to IkappaBalpha,
      resulting in near-complete inhibition of nuclear localization and transcriptional
      activation. Combined solution biophysical measurements and quantitative protein
      half-life measurements inside cells have allowed us to understand how the
      inhibition occurs, why IkappaBalpha can be degraded quickly in the free state but
      remain extremely stable in the bound state, and how signal activation and
      repression can be tuned by IkappaB folding dynamics. This review summarizes
      results of in vitro and in vivo experiments that converge demonstrating the
      effective interplay between biophysics and cell biology in understanding
      transcriptional control by the NF-kappaB signaling module.

PMID- 20055498
TI  - Hydrolytic deamination of 5,6-dihydrocytosine in a protic medium: a theoretical
      study.
AB  - The mechanism for the deamination reaction of 5,6-dihydrocytosine with H(2)O in a
      protic medium was investigated by DFT calculations at the B3LYP/6-311G(d,p) level
      of theory as a model reaction for the deamination reaction of 5,6-saturated
      cytosine derivatives. Two pathways were found. Pathway dhA, which can explain the
      deamination in a protic medium at acidic pH, and pathway dhBt, more
      representative of the reaction in a protic medium at neutral pH. Pathway dhA is a
      two-step mechanism initiated by the nucleophilic addition of a water molecule to
      carbon C4 of N3-protonated 5,6-dihydrocytosine with the assistance of a second
      water molecule, followed by elimination of an ammonium cation to form 5,6
      dihydrouracil. The nucleophilic addition is rate-determining with an activation
      free energy of 116.0 kJ/mol in aqueous solution. Pathway dhBt is a four-step
      mechanism which starts with the water-assisted tautomerization of 5,6
      dihydrocytosine to form the imino tautomer. This intermediate undergoes
      nucleophilic addition of water to carbon C4, which after protonation eliminates
      an ammonium cation, as in pathway dhA. The nucleophilic addition is again rate
      determining, with an activation free energy of 113.3 kJ/mol in aqueous solution.
      The latter value is about 25 kJ/mol lower than its counterpart for cytosine, in
      agreement with the experimental observation that 5,6-saturated cytosine
      derivatives exhibit a much shorter lifetime in aqueous solution than their
      unsaturated counterparts. The evaluation of reactivity indices derived from
      conceptual DFT leads to the conclusion that this lower activation free energy can
      be attributed to a larger local electrophilic power of carbon C4 in 5,6-saturated
      derivatives.

PMID- 20055497
TI  - Structure and ligand binding properties of the epoxidase component of styrene
      monooxygenase .
AB  - Styrene monooxygenase (SMO) is a two-component flavoprotein monooxygenase that
      transforms styrene to styrene oxide in the first step of the styrene catabolic
      and detoxification pathway of Pseudomonas putida S12. The crystal structure of
      the N-terminally histidine-tagged epoxidase component of this system, NSMOA,
      determined to 2.3 A resolution, indicates the enzyme exists as a homodimer in
      which each monomer forms two distinct domains. The overall architecture is most
      similar to that of p-hydroxybenzoate hydroxylase (PHBH), although there are some
      significant differences in secondary structure. Structural comparisons suggest
      that a large cavity open to the surface forms the FAD binding site. At the base
      of this pocket is another cavity that likely represents the styrene binding site.
      Flavin binding and redox equilibria are tightly coupled such that reduced FAD
      binds apo NSMOA approximately 8000 times more tightly than the oxidized coenzyme.
      Equilibrium fluorescence and isothermal titration calorimetry data using benzene
      as a substrate analogue indicate that the oxidized flavin and substrate analogue
      binding equilibria of NSMOA are linked such that the binding affinity of each is
      increased by 60-fold when the enzyme is saturated with the other. A much weaker
      approximately 2-fold positive cooperative interaction is observed for the linked
      binding equilibria of benzene and reduced FAD. The low affinity of the substrate
      analogue for the reduced FAD complex of NSMOA is consistent with a preferred
      reaction order in which flavin reduction and reaction with oxygen precede the
      binding of styrene, identifying the apoenzyme structure as the key catalytic
      resting state of NSMOA poised to bind reduced FAD and initiate the oxygen
      reaction.

PMID- 20055499
TI  - Influence of explicit hydration waters in calculating the hydrolysis constants
      for geochemically relevant metals.
AB  - The effect of including a second, explicit solvation shell of water molecules is
      examined on the DFT calculation of a selection of aquo-metal ions' pK(a) values
      (deprotonation constants). Our goal is to gauge the accuracy of how certain
      cluster approximations and implicit solvation models (PCM or COSMO) affect the
      results. The ions in this study include: Al(3+)((aq)); Fe(3+)((aq));
      Cr(3+)((aq)); Mn(3+)((aq)); Co(3+)((aq)); Ga(3+)((aq)); Fe(2+)((aq));
      Mg(2+)((aq)); and Be(2+)((aq)). Overall, we find that experimental pK(a)
      constants can be calculated successfully to within 1-2 pH units, provided a
      consistent hydration structure is maintained for products and reactants.

PMID- 20055501
TI  - Versatile strategy to access tricycles related to quassinoids and triterpenes.
AB  - The reactivity of two new bicyclic cyclohexenones (13 and 27) with several
      Nazarov reagents is presented. A flexible synthetic strategy is developed and
      provides access to highly substituted tricycles related to quassinoids and
      triterpenes.

PMID- 20055500
TI  - Diverse methyl sulfone-containing benzo[b]thiophene library via iodocyclization
      and palladium-catalyzed coupling.
AB  - Parallel solution-phase methods for the synthesis of a 72-membered
      benzo[b]thiophene library are reported. Medicinally interesting, drug-like,
      methyl sulfone-substituted benzo[b]thiophenes have been prepared by the palladium
      catalyzed substitution of 3-iodobenzo[b]thiophenes by Suzuki-Miyaura,
      Sonogashira, Heck, carboalkoxylation, and aminocarbonylation chemistry. The key
      intermediates for library generation, methyl sulfone-containing 3
      iodobenzo[b]thiophenes, are readily prepared by iodocyclization and oxidation
      methodologies from readily available alkynes.

PMID- 20055502
TI  - Liquid-crystalline self-organization of isocyanide-containing dendrimers induced
      by coordination to gold(I) fragments.
AB  - Dendritic polyisocyanides can be considered as promising polytopic ligands to
      generate a great diversity of metallodendrimers due to the ability of the
      isocyanide moiety to bind to various transition metals. Here, new isocyanide
      containing dendrimers and their corresponding polynuclear gold complexes have
      been prepared, [G(i)(NC)(Z)] and [G(i)(NCAuR)(Z)], respectively, where G(i) is a
      poly(phenyl ether) dendrimer, i is the generation number (i = 0, 1, or 2), Z is
      the number of peripheral groups (Z = 3 x 2(i)), and AuR are the surface groups
      ([R = Cl, C[triple bond]C-C(6)H(4)-OC(12)H(25), C[triple
      bond]CC(6)H(2)(OC(12)H(25))(3)]. The compounds are derived from a highly flexible
      phenyl ether-based dendritic core, G(i), having the general formula G(0) =
      C(6)H(3)(OC(11)H(22)OC(6)H(4)-)(3), G(1) =
      C(6)H(3)[OC(11)H(22)OC(6)H(3)(OC(11)H(22)OC(6)H(4)-)(2)](3), G(2) =
      C(6)H(3)[OC(11)H(22)OC(6)H(3){OC(11)H(22)OC(6)H(3)(OC(11)H(22)OC(6)H(4)
      )(2)}(2)](3)), growing from the trivalent phloroglucinol and with undecylene
      aliphatic spacers between each branching benzene ring and end-functionalized by
      isocyanide groups. As in their monomeric model counterparts, stable liquid
      crystalline phases are induced upon complexation of the AuR gold moieties at the
      branch termini. The nature of the anionic ligand R promotes the appearance of
      smectic or columnar mesophases, the formation of which are governed by steric and
      dipolar interactions. Based on X-ray diffraction experiments, models describing
      the supramolecular organization of these metallodendrimers into smectic and
      columnar mesophases are proposed: columnar phases result from the one-dimensional
      stacking of molecular disks made of self-assembled supermolecules in oblate
      cylindrical conformation, while the smectic phases form by the lateral two
      dimensional registry of the supermolecules in antiparallel head-to-head prolate
      conformation.

PMID- 20055503
TI  - Biobased nanocomposites from layer-by-layer assembly of cellulose nanowhiskers
      with chitosan.
AB  - A new biodegradable nanocomposite was obtained from layer-by-layer (LBL)
      technique using highly deacetylated chitosan and eucalyptus wood cellulose
      nanowhiskers (CNWs). Hydrogen bonds and electrostatic interactions between the
      negatively charged sulfate groups on the whisker surface and the ammonium groups
      of chitosan were the driving forces for the growth of the multilayered films. The
      film growth was followed by UV-vis spectroscopy through the maximum value of the
      absorption band at 194 nm and showed the deposition of 14.7 mg.m(-2) of chitosan
      polymer in each cycle. Scanning electron microscopy showed high density and
      homogeneous distribution of CNWs adsorbed on each chitosan layer. Cross-section
      characterization of the assembled films indicates an average of approximately 7
      nm of thickness per bilayer. The results presented in this work indicate that the
      methodology used can be extended to different biopolymers for the design of new
      biobased nanocomposites in a wide range of applications such as biomedical and
      food packaging.

PMID- 20055504
TI  - Structures and spectroscopic properties of fluoroboron-subtriazaporphyrin
      derivatives: density functional theory approach on the benzo-fusing effect.
AB  - Density functional theory (DFT) and time-dependent density functional theory
      (TDDFT) calculations were carried out to comparatively study the molecular
      structures, atomic charges, molecular orbitals, and electronic absorption spectra
      of fluoroboron-subtriazaporphyrin (SubTAP) and fluoroboron-subphthalocyanine
      (SubPc) as well as their benzo-fused low-symmetrical derivatives A(a)B(b)C(c) (3
      > or = a, b, c > or = 0). The peripherally fused benzene rings are revealed to
      have a significant effect on the structure and charge density distribution of the
      inner nitrogen atoms of subtriazaporphyrin core, while the charge of the central
      fluoroboron group changes very little. The effect of peripherally fused benzene
      rings on the frontier molecular orbitals of different compounds is comparatively
      discussed. The nature of the electron excitation between the frontier molecular
      orbitals of the 20 compounds is assigned according to the calculation results.
      The benzene rings fused directly onto pyrrole rings have been revealed to show
      more effect on the inner nitrogen atom than the outer benzene rings fused onto
      the periphery of isoindole rings. The present work will be helpful toward
      systematically understanding the effect of ring enlargement through
      asymmetrically fusing benzene ring(s) onto the subtriazaporphyrin skeleton on the
      structures and properties of fluoroboron-subtriazaporphyrin and fluoroboron
      subphthalocyanine analogues.

PMID- 20055505
TI  - Quantum chemical modeling of methanol oxidation mechanisms by methanol
      dehydrogenase enzyme: effect of substitution of calcium by barium in the active
      site.
AB  - Previous experimental studies have shown that the activation energy for methanol
      oxidation by naturally occurring Ca(2+)-containing methanol dehydrogenase (MDH)
      enzyme is double the methanol activation energy by Ba(2+)-MDH. However, neither
      the reason for this difference nor the specific transition states and
      intermediates involved during the methanol oxidation by Ba(2+)-MDH have been
      clearly stated. Hence, an MDH active site model based on the well-documented X
      ray crystallographic structure of Ca(2+)-MDH is selected, where the Ca(2+) is
      replaced by a Ba(2+) ion at the active site center, and the addition-elimination
      (A-E) and hydride-transfer (H-T) methanol oxidation mechanisms, already proposed
      in the literature for Ca(2+)-MDH, are tested for Ba(2+)-MDH at the BLYP/DNP
      theory level. Changes in the geometries and energy barriers for all the steps are
      identified, and qualitatively, similar (when compared to Ca(2+)-MDH)
      intermediates and transition states associated with each step of the mechanisms
      are found in the case of Ba(2+)-MDH. For both the A-E and H-T mechanisms, almost
      all the free-energy barriers associated with all of the steps are reduced in the
      presence of Ba(2+)-MDH, and they are kinetically feasible. The free energy
      barriers for methanol oxidation by Ba(2+)-MDH, particularly for the rate-limiting
      steps of both mechanisms, are almost half the corresponding barriers calculated
      for the case of Ca(2+)-MDH, which is in agreement with experimental observations.

PMID- 20055506
TI  - Competitive electron transfer and enhanced intersystem crossing in photoexcited
      covalent TEMPO-perylene-3,4:9,10-bis(dicarboximide) dyads: unusual spin
      polarization resulting from the radical-triplet interaction.
AB  - A stable 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) radical was covalently
      attached at its 4-position to the imide nitrogen atom of a perylene-3,4:9,10
      bis(dicarboximide) (PDI) to produce TEMPO-PDI, 1, having a well-defined distance
      and orientation between TEMPO and PDI. Transient optical absorption experiments
      in toluene following selective photoexcitation of the PDI chromophore in TEMPO
      PDI show that enhanced intersystem crossing occurs with tau = 45 +/- 1 ps,
      resulting in formation of TEMPO-(3*)PDI, while the same experiment in THF shows
      that the electron-transfer reaction TEMPO-(1*)PDI --> TEMPO(+*)-PDI(-*) occurs
      with tau = 1.2 +/- 0.2 ps and thus competes effectively with enhanced intersystem
      crossing. Time-resolved EPR (TREPR) spectroscopy on the photogenerated three-spin
      system TEMPO-(3*)PDI in toluene at 295 K initially shows a broad signal assigned
      to spin-polarized (3*)PDI, which thermalizes at longer times and is accompanied
      by formation of an emissively polarized TEMPO radical. No signals are observed in
      THF at 295 K. The TREPR spectrum of TEMPO-(3*)PDI at 85 K in toluene shows an
      emissive/absorptive signal due to TEMPO and a broad triplet signal due to (3*)PDI
      having a spin polarization pattern characteristic of overpopulation of its T(0)
      sublevel. This unusual spin polarization pattern does not result from radical
      pair intersystem crossing because electron transfer does not occur at 85 K. The
      observed spin polarization of (3*)PDI cannot be readily explained by mechanisms
      discussed previously, leading us to propose a new spin polarization mechanism,
      which requires that the radical and attached triplet are in the weak exchange
      regime.

PMID- 20055507
TI  - Recognition of some lanthanides, actinides, and transition- and heavy-metal
      cations by N-donor ligands: thermodynamic and kinetic aspects.
AB  - The remarkable actinide(III) selectivity of the polyaromatic N-donors bis
      triazine-pyridines (BTPs), hemi-bis-triazine-pyridines (hemi-BTPs) and bis
      triazine-bipyridines (BTBPs) make these ligands the most promising candidates in
      partitioning and transmutation processes developed so far to better manage
      nuclear waste. The interactions of n-Pr-BTP, C(5)-hemi-BTP, and the two most
      extensively investigated BTBPs (C(5)-BTBP and CyMe(4)-BTBP) have been studied
      with some representative lanthanide(III), uranyl, thorium, and transition- and
      other heavy-metal cations in methanol. The formation of complexes of different
      stoichiometries, the stability of which depended on both the ligands and the
      cations, was shown using UV absorption spectrophotometry. Study of the
      complexation reactions of La(3+), Eu(3+) and Yb(3+) with these four ligands by
      stopped-flow spectrophotometry allowed determination of the rate constants and
      postulation of possible complexation mechanisms.

PMID- 20055508
TI  - Cation coordination control of anionic group alignment to maximize SHG effects in
      the BaMBO(3)F (M = Zn, Mg) series.
AB  - Two new noncentrosymmtric fluoroborates, BaZnBO(3)F and BaMgBO(3)F, have been
      synthesized and characterized. It is found that BaZnBO(3)F possesses a P6 space
      group with cell parameters of a = 5.0657(1) A, c = 4.2800(1) A, and Z = 1. The
      structure is built up by five coordinated trigonal bipyramidal ZnO(3)F(2)
      polyhedra and triangular BO(3) groups. The ZnO(3)F(2) bipyramid shares its three
      equatorial oxygen atoms with three separate BO(3) groups to form a ZnO(3)-BO(3)
      layer, and the layers are linked by the apical fluorine atoms in the third
      dimension. Owing to its special coordination, ZnO(3)F(2) forces its three
      neighboring BO(3) groups to arrange into a perfect parallel alignment in the
      plane to give maximum contribution to the nonlinear optical (NLO) effect. Both
      calculation and powder second harmonic generation tests show that its effective
      NLO coefficient is on about the same order as that of LiB(3)O(5). In contrast, in
      BaMgBO(3)F, which crystallizes in space group Cc with a = 17.614(3) A, b =
      30.546(6) A, c = 8.060(2) A, and beta = 90.008(2) degrees , Mg coordinates to
      four oxygen and two fluorine atoms to form a severely distorted MgO(4)F(2)
      octahedron. It also uses four equatorial oxygen atoms, sharing with three BO(3)
      groups to form a MgO(4)-BO(3) layer, and again the layers are linked by the
      apical F atoms. Every Mg atom links with one edge-sharing and two corner-sharing
      BO(3) groups, leaving the BO(3) group misaligned and resulting in most of their
      contributions to NLO effects being canceled.

PMID- 20055509
TI  - Facile synthesis and luminescence of Sr(5)(PO(4))(3)Cl:Eu(2+) nanorod bundles via
      a hydrothermal route.
AB  - Sr(5)(PO(4))(3)Cl:Eu(2+) nanorod bundles were successfully prepared through a
      facile hydrothermal method. The X-ray diffraction (XRD) and FT-IR results
      demonstrate that the product is a pure hexagonal phase of Sr(5)(PO(4))(3)Cl. The
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and
      high-resolution TEM (HRTEM) images indicate that the as-prepared
      Sr(5)(PO(4))(3)Cl:Eu(2+) nanorod bundles consist of parallel nanorods with
      diameters ranging from 20 to 30 nm and that the nanorods grow along the [002]
      direction. The photoluminescence spectra show that the Eu(3+) ions have been
      reduced to Eu(2+) ions successfully and that the as-obtained
      Sr(5)(PO(4))(3)Cl:Eu(2+) phosphor exhibited intense blue emission. Furthermore,
      this new simple synthetic route may be of much significance in the synthesis of
      other divalent europium ions activated nanoscale phosphors by aqueous method.

PMID- 20055510
TI  - Surface science of soft scorpionates.
AB  - The chemisorption of the soft scorpionate Li[PhTm(Me)] onto silver and gold
      surfaces is reported. Surface enhanced Raman spectroscopy in combination with the
      Raman analysis of suitable structural models, namely, [Cu(kappa(3)-S,S,S
      PhTm(Me))(PCy(3))], [Ag(kappa(3)-S,S,S-PhTm(Me))(PCy(3))], [Ag(kappa(2)-S,S
      PhTm(Me))(PEt(3))], and [Au(kappa(1)-S-PhTm(Me))(PCy(3))], are employed to
      identify the manner in which this potentially tridentate ligand binds to these
      surfaces. On colloidal silver surface-enhanced Raman spectroscopy (SERS) spectra
      are consistent with PhTm(Me) binding in a didentate fashion to the surface,
      holding the aryl group in close proximity to the surface. In contrast, on gold
      colloid, we observe that the species prefers a monodentate coordination in which
      the aryl group is not in close proximity to the surface.

PMID- 20055512
TI  - Free-radical chemistry of disinfection byproducts. 3. Degradation mechanisms of
      chloronitromethane, bromonitromethane, and dichloronitromethane.
AB  - Halonitromethanes (HNMs) are byproducts formed through ozonation and chlorine/
      chloramine disinfection processes in drinking waters that contain dissolved
      organic matter and bromide ions. These species occur at low concentration but
      have been determined to have high cytotoxicity and mutagenicity and therefore may
      represent a human health hazard. In this study, we have investigated the
      chemistry involved in the mineralization of HNMs to nonhazardous inorganic
      products through the application of advanced oxidation and reduction processes.
      We have combined measured absolute reaction rate constants for the reactions of
      chloronitromethane, bromonitromethane, and dichloronitromethane with the hydroxyl
      radical and the hydrated electron with a kinetic computer model in an attempt to
      elucidate the reaction pathways of these HNMs. The results are compared to
      measurements of stable products resulting from steady-state (60)Co gamma
      irradiations of the same compounds. The model predicted the decomposition of the
      parent compounds and ingrowth of chloride and bromide ions with excellent
      accuracy, but the prediction of the total nitrate ion concentration was slightly
      in error, reflecting the complexity of nitrogen oxide species reactions in
      irradiated solution.

PMID- 20055513
TI  - Reorientations of aromatic amino acids and their side chain models: anisotropy
      measurements and molecular dynamics simulations.
AB  - We present a study of reorientation dynamics of the three aromatic amino acids
      and their side chain models in aqueous solution. Experimentally, anisotropy decay
      measurements with picosecond time resolution were performed for blocked
      tryptophan, tyrosine, and phenyalanine and model compounds p-cresol and 3
      methylindole. Computationally, rotational diffusion was modeled by molecular
      dynamics simulations for the three aromatic residues and their side chain models:
      benzene, toluene, phenol, p-cresol, indole, and 3-methylindole in explicit water.
      Our simulations used the CHARMM protein force field and associated TIP3P water
      model and tend to underestimate the rotational correlation times. However, the
      simulations yield several interesting qualitative insights into reorientational
      motions that complement the experimental measurements. The effects of substituent
      and temperature on reorientations of the parent compounds are well reproduced
      computationally. Additionally, simulations indicate strongly anisotropic
      reorientations for most of the studied compounds and a separation of time scales
      between conformational dynamics and rotational diffusion. Comparison with
      continuum hydrodynamic models suggests that we may consider that the blocked
      amino acids move under stick boundary conditions, while the dynamics for most of
      the model compounds falls between stick and slip conditions. Our systematic
      treatment of blocked amino acids, starting from the parent compounds (benzene,
      phenol, and indole) provides a baseline for understanding the anisotropy decay
      signals of more complicated peptide systems.

PMID- 20055514
TI  - Low temperature infrared spectroscopy study of pyrazinamide: from the isolated
      monomer to the stable low temperature crystalline phase.
AB  - A structural and spectroscopic analysis of the anti-tuberculosis drug
      pyrazinamide (PZA) was carried out. The PZA molecule was predicted theoretically
      to possess two conformers differing by internal rotation around the C-C(
      horizontal lineO) bond, with the E conformer (C(s) symmetry point group; N-C-C
      horizontal lineO dihedral: 180 degrees ) being ca. 30 kJ mol(-1) more stable than
      the Z form (C(1) point group; N-C-C horizontal lineO dihedral: ca. +/- 42 degrees
      ). In consonance with both the large energy difference and low energy barrier
      between the Z and E conformers, upon isolation in low temperature argon and xenon
      matrices, only the E form could be observed and characterized spectroscopically.
      In the argon matrix, this conformer was found to exist in at least three matrix
      sites, of different stability. In a supersonic jet, besides the monomer (E), the
      most stable dimer of PZA with two equivalent NH...O horizontal line hydrogen
      bonds could also be identified. Its spectrum reveals rapid energy flow out of the
      excited NH stretching mode mediated by one of the heteroatoms in the ring.
      Finally, the IR spectra of the amorphous solid resulting from fast cooling of the
      vapor of the compound (initially in the alpha crystalline phase) onto the cold
      substrate of the cryostat (10 K) and of the crystalline phase resulting from
      warming the amorphous solid were also recorded and interpreted. The obtained
      crystalline phase was found to be the thermodynamically most stable delta
      polymorph of PZA.

PMID- 20055515
TI  - Kinetic model of the H(2)O(2)-SCN(-)-OH(-)-Cu(2+) oscillator and its application
      to the interpretation of the potentiometric responses of various inert electrodes
      monitoring the reaction course.
AB  - The high complexity of the kinetic mechanism of the H(2)O(2)-SCN(-)-OH(-)-Cu(2+)
      oscillator, involving numerous intermediates, causes the oscillations monitored
      potentiometrically with gold or glassy carbon electrodes to exhibit opposite
      phases compared with the oscillations recorded with palladium or platinum
      electrodes. Following our previous work on the outline explanation of these
      phenomena, involving the concept of the mixed potential, in this paper, we
      present their more detailed and advanced study. For that purpose, we built up a
      simplified but realistic kinetic model of the studied oscillator, involving nine
      intermediates. Of those nine species, Cu(OH)(3)(-), Cu(OH)(2)(-), and HO(2)(*)
      were found to be crucial for the explanation of the potentiometric responses of
      various electrodes, under an additional assumption that the interfacial exchange
      current density of the HO(2)(*)/HO(2)(-) couple increases in the series GC < Au <
      Pt. Calculated oscillatory variations of the mixed potential for various model
      electrodes, compared with experimental results, allowed us to conclude that the
      potentiometric oscillations are caused largely by the oscillations of the
      [Cu(OH)(3)(-)]/[Cu(OH)(2)(-)] concentration ratio, irrespective of the electrode
      material used as a potentiometric sensor. For the Au electrode, the increase of
      the potential within every oscillatory peak largely reflects the increase in the
      [Cu(OH)(3)(-)]/[Cu(OH)(2)(-)] ratio. The simultaneous shift of the relatively
      high Pt electrode potential toward more negative equilibrium potential of the
      Cu(OH)(3)(-)/Cu(OH)(2)(-) couple is caused by the increase of the exchange
      current density of the latter couple. Thus, even the opposite phases of the
      potentiometric oscillations are explainable in terms of the oscillatory behavior
      of the same redox couple. Understanding of such phenomena is crucial for the
      proper interpretation of potentiometric data in complex chemical systems.

PMID- 20055516
TI  - Observation of the A-X electronic transitions of cyclopentyl and cyclohexyl
      peroxy radicals via cavity ringdown spectroscopy.
AB  - The A-X electronic absorption spectra of cyclopentyl, cyclohexyl, and cyclohexyl
      d(11) peroxy radicals have been recorded at room temperature by cavity ringdown
      spectroscopy. By comparing the experimental spectra with predictions from ab
      initio and density functional calculations, we have assigned the band origins and
      vibrational structure of each of these species. The spectrum of cyclopentyl
      peroxy is interpreted primarily in terms of two overlapping gauche conformers,
      while that of cyclohexyl peroxy appears to be a superposition of axially and
      equatorially substituted gauche conformers, both based on the chair conformation
      of cyclohexane. Expectations from calculated Boltzmann factors indicate
      comparable populations for cis-conformers; however, no bands uniquely assignable
      to cis-conformers of either peroxy can be identified. Plausible assignments for
      cis-conformers are considered, and possible explanations for their absence are
      offered, including specifically lower oscillator strengths than for the gauche
      conformers. Mode mixing appears to be responsible for the appearance of multiple
      vibrations with COO bending character for both peroxies, particularly for
      cyclohexyl peroxy.

PMID- 20055517
TI  - Heats of formation of t-butyl peroxy radical and t-butyl diazyl ion: RRKM vs
      SSACM rate theories in systems with kinetic and competitive shifts.
AB  - The dissociations of energy-selected di-t-butyl peroxide and di-t-butyl diazene
      ions have been studied by threshold photoelectron-photoion coincidence (TPEPICO)
      spectroscopy. Di-t-butyl peroxide ions dissociate via two parallel channels: (1)
      methyl loss at a 0 K onset (E0) of 9.58 +/- 0.04 eV followed by a sequential
      dissociation of the daughter ion to produce C4H9O+ and acetone; and (2) the
      dominant dissociation channel, producing t-butyl ion and t-butyl peroxy radical
      at an E0 of 9.758 +/- 0.020 eV. Di-t-butyl diazene ions dissociate through three
      parallel channels: (1) a rearrangement to form isobutene ion; (2) C-N bond
      cleavage with the charge staying on the t-butyl diazyl species (E0 = 8.069 +/-
      0.050 eV); and (3) C-N bond cleavage with the charge instead on the t-butyl (E0 =
      8.122 +/- 0.050 eV); the coproduct for this latter channel is a weakly, or
      possibly unbound, N2...t-butyl structure. Both the peroxide and diazene ion
      dissociations produce metastable daughters, and the dissociation rates are
      modeled with two rate theories: the Rice-Ramsperger-Kassel-Marcus (RRKM) theory
      and a simplified version of the statistical adiabatic channel model (SSACM). Due
      to a large kinetic shift, RRKM incorrectly models the peroxide ion rate curve.
      Using SSACM, the heat of formation of t-butyl peroxy radical is determined to be
      DeltaH0Kdegrees = - 81.1 +/- 3.9 kJ mol-1, and, using B3LYP/6-311++G(d,p) thermal
      energy, DeltaH298Kdegrees = - 109.7 +/- 3.9 kJ mol-1. Due to a competitive shift
      of the higher energy channel onsets, RRKM also incorrectly models the diazene
      rate curves. The 298 K heat of formation of the t-butyl diazyl ion, which is
      bound by 14 kJ mol-1, is determined to be 701.2 +/- 5.9 kJ mol-1.

PMID- 20055518
TI  - High field (33)S solid state NMR and first-principles calculations in potassium
      sulfates.
AB  - A set of potassium sulfates presenting a variety of sulfur environments
      (K(2)SO(4), KHSO(4), K(2)S(2)O(7), and K(2)S(2)O(8)) has been studied by (33)S
      solid state NMR at 21 T. Low natural abundance (0.75%) and small gyromagnetic
      ratio of (33)S presented a serious challenge even at such a high magnetic field.
      Nevertheless, using the QCPMG technique we were able to obtain good signals from
      the sites with C(Q) values approaching 16 MHz. Assignment of the sites and the
      relative orientations of the EFG tensors were assisted by quantum mechanical
      calculations using the Gaussian 98 and CASTEP packages. The Gaussian 98
      calculations were performed using the density functional method and gauge
      independent atomic orbitals on molecular clusters of about 100-120 atoms. The
      CASTEP calculations utilized periodic boundary conditions and a gauge-including
      projector augmented-wave pseudopotential approach. Although only semiquantitative
      agreement is observed between the experimental and calculated parameters, the
      calculations are a very useful aid in the interpretation of experimental data.

PMID- 20055519
TI  - A reliable and efficient first principles-based method for predicting pK(a)
      values. 2. Organic acids.
AB  - In part 1 of this series, we developed a protocol for the large-scale calculation
      of pK(a) values in aqueous solutions from first principles calculations, with the
      goal of striking a compromise between accuracy and computational efficiency.
      Following previous workers in the field, pK(a) values are calculated from a
      linear regression fit to deprotonation energies: pK(a)(f) = alpha(f)(E(A)(-) -
      E(HA)) + beta(f), where f denotes a family of functional groups. In this paper,
      we derive (alpha(f), beta(f)) values for the acidic functional groups -COOH, 
      POOH, alcoholic and phenolic -OH, -SH, -NHOH/ horizontal lineNOH, and -NROH,
      using a data set of 449 experimental pK(a) values. Several groupings of these
      functional groups were explored; our final recommended method uses five families
      (10 empirical parameters). Mean absolute deviations between our fits and
      experiment are 0.4 pK(a) units or less for each with a maximum error range of +/
      1.5 pK(a) units. In certain subgroups, such as monocarboxylic acids, considerably
      better fits (mean absolute deviation approximately 0.20 pK(s) units) were
      obtained at the cost of more empirical parameters. Almost 70% of pK(a)'s
      calculated by our protocol lie within +/-0.4 pK(a) units and over 90% within +/
      0.8 pK(a) units of the experimental reference value. Our results compare
      favorably with previous similar models which have greater computational cost.

PMID- 20055520
TI  - Structural study of selected polyhalogenated benzimidazoles (protein kinase CK2
      inhibitors) by nuclear quadrupole double resonance, X-ray, and density functional
      theory.
AB  - Protein kinase CK2 inhibitors, polyhalogenated benzimidazoles, have been studied
      experimentally in solid state by NMR-NQR double resonance and X-ray and
      theoretically by the density functional theory (DFT). Six resonance frequencies
      on (14)N have been detected and assigned to particular nitrogen sites in each
      polyhalogenated benzimidazole molecule. The effects of prototropic annular
      tautomerism and polymorphism related to stable cluster formation due to
      intermolecular hydrogen bonding interactions on the (14)N NQR parameters have
      been analyzed within the DFT and AIM (atoms in molecules) formalism. The studies
      suggest that all polyhalogenobenzimidazoles are isostructural and can exhibit
      polymorphism and that (14)N NQR is very sensitive to hydrogen bondings but less
      sensitive to the specific arrangement of the hydrogen bonded molecules. NQDR and
      DFT results suggest the presence of the prototropic annular tautomerism 50:50,
      which is in a good agreement with the X-ray and (1)H NMR data.

PMID- 20055521
TI  - Energy barriers of vinylidene carbene reactions from the anti-hermitian
      contracted Schrodinger equation.
AB  - Computational studies of carbenes must take into account the possibility of
      multireference correlation because the highest occupied and lowest unoccupied
      molecular orbitals can be nearly energetically degenerate. We apply the anti
      Hermitian contracted Schrodinger equation (ACSE) [Mazziotti, D. A. Phys. Rev.
      Lett. 2006, 97, 143002] to compute two-electron reduced density matrices (2-RDMs)
      and their energies for two carbene reactions: (i) the acetylene-vinylidene
      rearrangement and (ii) the rearrangement of pent-1-en-4-yn-3-one to
      acryloylvinylidene, which then cyclizes to cyclopenta-2,4-dienone. The ACSE has
      some unique advantages in the treatment of carbene reactions and more general
      families of reactions in which the importance of multireference correlation is
      not known a priori: (i) the ACSE is more reliable than single-reference methods
      for confirming the presence or absence of multireference correlation and (ii) in
      the absence of multireference correlation, unlike multireference second-order
      perturbation theory (MRPT2), the ACSE recovers more single-reference correlation
      energy than similarly scaling coupled-cluster methods. Because MRPT2 does not
      recover as much single-reference correlation as the coupled-cluster or ACSE
      methods, it tends to underestimate reaction barriers within the carbene
      reactions. For example, in the rearrangement of pent-1-en-4-yn-3-one, the ACSE
      and CCSD(T) methods produce cyclization barriers of 18.9 and 18.7 kcal/mol with
      the 6-31G(d) basis set, whereas MRPT2 predicts this barrier to be 12.1 kcal/mol;
      furthermore, both the ACSE and CCSD(T) determine the energy of the transition
      state for acryloylvinylidene formation to be 6.6-6.7 kcal/mol above that of the
      carbene, and yet, MRPT2 does not predict a transition state.

PMID- 20055522
TI  - Alternative Kullback-Leibler information entropy for enantiomers.
AB  - In our series of studies on quantifying chirality, a new chirality measure is
      proposed in this work based on the Kullback-Leibler information entropy. The
      index computes the extra information that the shape function of one enantiomer
      carries over a normalized shape function of the racemate, while in our previous
      studies the shape functions of the R and S enantiomers were used considering one
      as reference for the other. Besides being mathematically more elegant (symmetric,
      positive definite, zero in the case of a nonchiral system), this new index bears
      a more direct relation with chirality oriented experimental measurements such as
      circular dichroism (CD) and optical rotation measurements, where the racemate is
      frequently used as a reference. The five chiral halomethanes holding one
      asymmetric carbon atom and H, F, Cl, Br, and I as substituents have been
      analyzed. A comparison with our calculated optical rotation and with Avnir's
      Continuous Chirality Measure (CCM) is computed. The results show that with this
      index the emphasis lies on the differences between the noncoinciding
      substituents.

PMID- 20055524
TI  - Facile fabrication of efficient organic CMOS circuits.
AB  - Organic electronic circuits based on a combination of n- and p-type transistors
      (so-called CMOS circuits) are attractive, since they promise the realization of a
      manifold of versatile and low-cost electronic devices. Here, we report a novel
      photoinduced transformation method, which allows for a particularly
      straightforward fabrication of highly functional organic CMOS circuits. A
      solution-deposited single-layer film, comprising a mixture of the n-type
      semiconductor [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) and the p-type
      semiconductor poly-3-hexylthiophene (P3HT) in a 3:1 mass ratio, was utilized as
      the common active material in an array of transistors. Selected film areas were
      exposed to laser light, with the result that the irradiated PCBM monomers were
      photochemically transformed into a low-solubility and high-mobility dimeric
      state. Thereafter, the entire film was developed via immersion into a developer
      solution, which selectively removed the nonexposed, and monomeric, PCBM
      component. The end result was that the transistors in the exposed film areas are
      n-type, as dimeric PCBM is the majority component in the active material, while
      the transistors in the nonexposed film areas are p-type, as P3HT is the sole
      remaining material. We demonstrate the merit of the method by utilizing the
      resulting combination of n-type and p-type transistors for the realization of
      CMOS inverters with a high gain of approximately 35.

PMID- 20055525
TI  - Viscosity of nanoconfined polyamide-6,6 oligomers: atomistic reverse
      nonequilibrium molecular dynamics simulation.
AB  - Our new simulation scheme in isosurface-isothermal-isobaric ensemble [Eslami, H.;
      Mozaffari, F.; Moghadasi, J.; Muller-Plathe, F. J. Chem. Phys. 2008, 129,
      194702], developed to simulate confined fluids in equilibrium with bulk, is
      applied to simulate polyamide-6,6 oligomers confined between graphite surfaces.
      The reverse nonequilibrium molecular dynamics simulation technique is employed to
      shear the graphite surfaces. In this work, six confined systems, with different
      surface separations, as well as the bulk fluid are simulated. Our results show a
      viscosity increase with respect to the bulk fluid, with decreasing distance
      between surfaces. Also, the calculated viscosities of the confined systems show
      an oscillatory behavior with maxima corresponding to well-formed layers between
      the surfaces. We observe a substantial slip at the surfaces, with the slip length
      depending on the shear rate and on the slit width. The slip length and the slip
      velocity show oscillatory behavior with out-of-phase oscillations with respect to
      the solvation force oscillations. Moreover, the temperature difference between
      coldest and hottest parts of the simulation box depends on the shear rate and on
      the layering effect (solvation force oscillations). An analysis of oligomer
      deformation under flow shows preferential alignment of oligomers parallel to the
      surfaces with increasing shear rate.

PMID- 20055526
TI  - Structural and energetic analysis on the complexes of clinically isolated subtype
      C HIV-1 proteases and approved inhibitors by molecular dynamics simulation.
AB  - HIV-1 has a large genetic diversity. Subtype B HIV-1 is commonly found in
      patients in developed countries. In contrast, an increasing number of patients
      are infected with the non-B subtype viruses, especially with subtype C HIV-1, in
      developing countries. It remains to be clarified how mutations or polymorphisms
      in non-B subtype HIV-1 influence the efficacy of the approved inhibitors. In this
      study, we have performed molecular dynamics simulations on clinically isolated
      subtype C HIV-1 proteases in complex with three kinds of approved inhibitors.
      From the structural and energetic viewpoints, we identified the polymorphisms
      influencing on the binding of the inhibitors. The effect of the V82I mutation on
      the association with chemicals and the reason for rare appearance of the D30N
      mutation in subtype C HIV-1 were discussed in terms of the change of geometry of
      the residues in HIV-1 protease.

PMID- 20055527
TI  - Oxidation and reduction products of X irradiation at 10 K in sucrose single
      crystals: radical identification by EPR, ENDOR, and DFT.
AB  - Electron paramagnetic resonance (EPR), electron nuclear double resonance (ENDOR),
      and ENDOR-induced EPR (EIE) measurements on sucrose single crystals at 10 K after
      in situ X irradiation at this temperature reveal the presence of at least nine
      different radical species. Nine proton hyperfine coupling tensors were determined
      from ENDOR angular variations and assigned to six of these species (R1-R6) using
      EIE. Spectral simulations indicate that four of those (R1-R3 and R6) dominate the
      EPR absorption. Assisted by periodic density functional theory (DFT)
      calculations, R1 and R2 are identified as H-abstracted C1- and C5-centered
      radicals, R3 is tentatively assigned to an H-abstracted C6-centered radical, and
      R6 is identified as an alkoxy radical where the abstracted hydroxy proton has
      migrated to a neighboring OH group via intermolecular proton transfer. The latter
      radical had been characterized and identified in a previous study, but the
      present DFT calculations provide additional insight into its conformation and
      particular properties. This study provides the first step in unraveling the
      formation mechanism of the stable sucrose radicals detected after room
      temperature irradiation and contributes to the understanding of the initial
      stages of radiation damage to solid-state carbohydrates.

PMID- 20055528
TI  - Prediction of immunogenicity of therapeutic proteins: validity of computational
      tools.
AB  - Most protein therapeutics have the potential to induce undesirable immune
      responses in patients. Many patients develop anti-therapeutic antibodies, which
      can affect the safety and efficacy of the therapeutic protein, particularly if
      the response is neutralizing. There are a variety of factors that influence the
      immunogenicity of protein therapeutics and, in particular, the presence of B- and
      T-cell epitopes is considered to be of importance. In silico tools to identify
      the location of both B- and T-cell epitopes and to assess the potential for
      immunogenicity have been developed, and such tools provide an alternative to more
      complex in vitro or in vivo immunogenicity assays. This article reviews
      computational epitope prediction methods and also the use of manually curated
      databases containing experimentally derived epitope data. However, due to the
      complexities of the molecular interactions involved in epitope recognition by the
      immune system, the heterogeneity of key proteins in human populations and the
      adaptive nature of the immune response, in silico methods have not yet achieved a
      level of accuracy that enables them to be used as stand-alone tools for
      predicting clinical immunogenicity. Computational methods, particularly with
      regard to T-cell epitopes, only consider a limited number of events in the
      process of epitope formation and therefore routinely over-predict the number of
      epitopes within a molecule. Epitope databases such as the Immune Epitope Database
      (IEDB) and the proprietary T Cell Epitope Database (TCED) have reached a size and
      level of organization that increases their utility; however, they are not
      exhaustive. These methods have greatest utility as an adjunct to in vitro assays
      where they can be used either to reduce the amount and complexity of the in vitro
      screening, or they can be used as tools to analyze the sequence of the identified
      epitope in order to locate amino acids critical for its properties.

PMID- 20055530
TI  - Pharmacokinetics and pharmacodynamics of monoclonal antibodies: concepts and
      lessons for drug development.
AB  - Monoclonal antibodies (mAbs) have complex pharmacology; pharmacokinetics and
      pharmacodynamics depend on mAb structure and target antigen. mAbs targeting
      soluble antigens often exhibit linear pharmacokinetic behavior, whereas mAbs
      targeting cell surface antigens frequently exhibit nonlinear behavior due to
      receptor-mediated clearance. Where nonlinear kinetics exist, clearance can change
      due to receptor loss following repeated dosing and/or disease severity. mAb
      pharmacodynamics are often indirect, with delayed clinically relevant outcomes.
      This behavior provides challenges during clinical development; studies must be
      carefully planned to account for complexities specific to each agent. Selection
      of a starting dose for human studies can be difficult. Species differences in
      pharmacology need to be considered. Various metrics are available for scaling
      from animals to humans. Optimal dose selection should ensure uniform mAb exposure
      across all individuals. Traditional approaches such as flat dosing and variable
      dosing based upon body surface area or weight should be supported by
      pharmacokinetic and pharmacodynamic behavior, including target antigen and
      concurrent disease states. The use of loading doses or dose adjustments to
      improve clinical response is also a consideration. The evaluation of drug
      interactions requires innovative designs. Due to the pharmacokinetic properties
      of mAbs, interacting drugs may need to be administered for protracted periods.
      Consequently, population pharmacokinetic and pharmacodynamic model-based
      approaches are often implemented to evaluate mAb drug interactions.

PMID- 20055531
TI  - Recombinant glucocerebrosidase (imiglucerase) as a therapy for Gaucher disease.
AB  - Imiglucerase is a recombinant formulation of human glucocerebrosidase, which is
      administered to patients with Gaucher disease (GD) as enzyme replacement therapy
      (ERT). Imiglucerase is generated from transduced Chinese hamster ovary cells, and
      modified by sequential deglycosylation of its carbohydrate side chains to expose
      alpha-mannosyl residues that mediate the uptake of the intravenously infused
      enzyme. The majority of patients initiate therapy on a fortnightly basis, using
      imiglucerase doses ranging from 30 to 60 U/kg bodyweight per infusion. Treatment
      has been shown to either stabilize or reverse several features of GD resulting
      from hematologic, visceral, and skeletal involvement. The treatment is well
      tolerated, and infusion-related adverse events such as pruritus and hives,
      observed primarily in patients who have developed antibodies to the exogenous
      enzyme, are readily managed. These findings have made ERT the standard of care
      for patients with GD type 1 (the non-neuronopathic form). Imiglucerase is also
      given to a majority of GD type 3 patients, as a means of assuaging their systemic
      problems. However, ERT has not been shown to eliminate the neurologic problems
      that these patients ultimately experience. Currently, two different enzyme
      formulations are in clinical trials. In addition, alternative therapeutic options
      are being explored as a substitute or complementary approach to ERT in the
      management of GD patients. The latter medications are oral agents that act to
      reduce substrate load either by inhibiting its synthesis or enhancing the
      residual activity of the endogenous mutant enzyme. Ongoing investigations are
      providing new insights into downstream mechanisms of disease, which may serve as
      further targets for adjunctive treatments. Cost of care considerations remain a
      topic of debate.

PMID- 20055529
TI  - Glycosylation of therapeutic proteins: an effective strategy to optimize
      efficacy.
AB  - During their development and administration, protein-based drugs routinely
      display suboptimal therapeutic efficacies due to their poor physicochemical and
      pharmacological properties. These innate liabilities have driven the development
      of molecular strategies to improve the therapeutic behavior of protein drugs.
      Among the currently developed approaches, glycoengineering is one of the most
      promising, because it has been shown to simultaneously afford improvements in
      most of the parameters necessary for optimization of in vivo efficacy while
      allowing for targeting to the desired site of action. These include increased in
      vitro and in vivo molecular stability (due to reduced oxidation, cross-linking,
      pH-, chemical-, heating-, and freezing-induced unfolding/denaturation,
      precipitation, kinetic inactivation, and aggregation), as well as modulated
      pharmacodynamic responses (due to altered potencies from diminished in vitro
      enzymatic activities and altered receptor binding affinities) and improved
      pharmacokinetic profiles (due to altered absorption and distribution behaviors,
      longer circulation lifetimes, and decreased clearance rates). This article
      provides an account of the effects that glycosylation has on the therapeutic
      efficacy of protein drugs and describes the current understanding of the
      mechanisms by which glycosylation leads to such effects.

PMID- 20055532
TI  - The role of endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis.
AB  - The endothelin system participates in a number of critical biologic pathways,
      including normal wound healing. In addition, emerging basic science, and animal
      and human data all suggest that endothelin-1 (EDN1, also known as ET-1) is a
      potentially important contributor in the pathobiology of fibrosing disorders,
      including those that affect the lung. For example, EDN1 drives fibroblast
      activation, proliferation, as well as differentiation into myofibroblasts -
      processes that lead to excessive collagen deposition. Patients with idiopathic
      pulmonary fibrosis (IPF) have increased levels of EDN1 in both their
      bronchoalveolar lavage fluid and lung tissue. Beyond this, rodent models suggest
      that endothelin receptor antagonists can limit bleomycin-induced lung fibrosis.
      This suggests a biologic rationale for the blockade of EDN1 to limit the
      evolution of lung fibrosis in humans. Initial results from a trial examining the
      efficacy of a dual endothelin receptor antagonist suggest that this approach may
      delay disease progression in a subset of patients with IPF.

PMID- 20055533
TI  - Basiliximab: a review of its use as induction therapy in renal transplantation.
AB  - Basiliximab (Simulect) is a recombinant chimeric murine/human IgG1 monoclonal
      anti-interleukin-2 receptor antibody that is indicated for the prevention of
      acute organ rejection in adult and pediatric renal transplant recipients in
      combination with other immunosuppressive agents. Induction therapy with two doses
      (day 0 and day 4) of intravenous basiliximab as part of double- or triple
      immunotherapy regimens in adult renal transplant recipients reduces acute
      rejection episodes without increasing the incidence of adverse events. Compared
      with rabbit-derived antithymocyte globulin (RATG), basiliximab is generally
      associated with similar efficacy in standard-risk patients, but reduced efficacy
      in high-risk patients. Initial results indicate that induction with basiliximab
      is associated with a higher rate of biopsy-proven acute rejection than
      alemtuzumab induction. Basiliximab is generally associated with a tolerability
      profile that is similar to that reported with placebo, and better than that
      reported with RATG. As with other induction agents, basiliximab has not
      demonstrated improved graft or patient survival over the long term (periods of up
      to 7 years). Basiliximab induction allows for reduced dosage of corticosteroids
      or calcineurin inhibitors, while maintaining adequate immunosuppression, thereby
      reducing the potential for adverse effects associated with these coadministered
      agents. Thus, basiliximab provides an effective, well tolerated option for the
      prophylaxis of acute renal transplant rejection.

PMID- 20055534
TI  - Task influences on the dynamic properties of fast eye movements.
AB  - It is widely debated whether fast phases of the reflexive optokinetic nystagmus
      (OKN) share properties with another class of fast eye movements, visually guided
      saccades. Conclusions drawn from previous studies were complicated by the fact
      that a subject's task influences the exact type of OKN: stare vs. look nystagmus.
      With our current study we set out to determine in the same subjects the exact
      dynamic properties (main sequence) of various forms of fast eye movements. We
      recorded fast phases of look and stare nystagmus as well as visually guided
      saccades. Our data clearly show that fast phases of look and stare nystagmus
      differ with respect to their main sequence. Fast phases of stare nystagmus were
      characterized by their lower peak velocities and longer durations as compared to
      fast phases of look nystagmus. Furthermore we found no differences between fast
      phases of stare nystagmus evoked with limited and unlimited dot lifetimes.
      Visually guided saccades were on the same main sequence as fast phases of look
      nystagmus, while they had higher peak velocities and shorter durations than fast
      phases of stare nystagmus. Our data underline the critical role of behavioral
      tasks (e.g., reflexive vs. intentional) for the exact spatiotemporal
      characteristics of fast eye movements.

PMID- 20055535
TI  - Contours in noise: a role for self-cuing?
AB  - A contour formed of aligned Gabor patches is easily detected amidst a dense
      background of randomly oriented patches; the longer the string of aligned
      patches, the more easily the contour is detected (D. J. Field, A. Hayes, & R. F.
      Hess, 1993). Here we show that a short string of collinear elements acts as a cue
      pointing to other patches of similar orientation that lie along the path defined
      by the string. Cueing might increase the gain of similarly oriented elements in
      the vicinity and/or reduce the number of potential locations (uncertainty) that
      the observer monitors. To assess the strength of the contour cue, I measured
      sensitivity to contrast increments on a test patch placed at various offsets
      relative to the cueing contour. Noise density and the length of cueing contour
      were also manipulated. Signal detection theory analysis of the psychometric
      function provided estimates of the gain and uncertainty parameters associated
      with each condition. In the presence of noise, observers were best at detecting a
      contrast increment on a patch that was aligned with the cueing string. Gain
      estimates were high for the aligned condition but decreased with increasing
      offset from this position. Uncertainty estimates were invariant with offset at a
      given noise level but increased with increasing noise. Uncertainty also decreased
      significantly when the length of the cueing string was increased. The high gain
      for collinear test patches and the ability of the contour to reduce uncertainty
      at high noise densities is indeed similar to the effect of an explicit cue (e.g.,
      Z.-L. Lu & B. A. Dosher, 1998), suggesting that one part of the contour cues
      other parts and contributes to the detectability of contours in noise.

PMID- 20055536
TI  - Speed encoding in human visual cortex revealed by fMRI adaptation.
AB  - In macaque visual cortex, the conventional view is that image motion is initially
      detected by direction-sensitive neurons that are tuned in terms of local spatial
      and temporal frequency (TF), from which speed is encoded later. We used
      functional magnetic resonance imaging (fMRI) adaptation to seek evidence for
      speed or TF tuning in human visual cortex. Drifting sine-wave gratings were
      presented in pairs (S1: adapter, 100% contrast; S2: probe, 15, 40 or 80%
      contrast). In each trial, either speed or TF was the same for S1 and S2, whereas
      the other dimension changed. We investigated whether the response was weaker
      (adapted) for repetitions of the same speed, indicating speed coding, or for
      repetitions of TF, indicating TF coding. For high-contrast (80%) probes, we
      observed clear speed coding in MT and MST with similar but weaker trends in
      several earlier visual areas. For medium- and low contrast probes, our data
      indicated a trend towards temporal frequency coding in most visual areas studied.
      In a second experiment, we adjusted stimuli in terms of perceived rather than
      physical speed and found a trend for speed coding even for low-contrast probes.
      Our results suggest that speed coding dominates in MT/MST for high contrast
      stimuli, and possibly also in other visual areas and/or at lower contrasts.

PMID- 20055537
TI  - Binocular rivalry: spreading dominance through complex images.
AB  - When different images are presented to the two eyes, each can intermittently
      disappear, leaving the other to dominate perception. This is called binocular
      rivalry. When using radial gratings, focal contrast increments can trigger a
      traveling wave of perceptual dominance change, originating at the locus of the
      contrast increment and circling the stimulus. This has been linked to a sweep of
      activity through V1 that can be traced via fMRI. The dominance of more complex
      images, like human faces, has been linked to higher level processing structures
      characterized by more holistic object centered properties. We therefore decided
      to assess how dominance would spread through more complex images. Using Kanisza
      squares and human faces we found that dominance tended to spread gradually away
      from the locus of the contrast increment, often along real or illusory contours.
      We also found that perceptual dominance was slow to spread between facial regions
      encoded by different monocular channels. These data are consistent with low-level
      monocular mechanisms, like those found in V1, playing a determinant role in the
      spread of perceptual dominance through complex images during binocular rivalry.

PMID- 20055538
TI  - A (fascinating) litmus test for human retino- vs. non-retinotopic processing.
AB  - In human vision, the optics of the eye map neighboring points of the environment
      onto neighboring photoreceptors in the retina. This retinotopic encoding
      principle is preserved in the early visual areas. Under normal viewing
      conditions, due to the motion of objects and to eye movements, the retinotopic
      representation of the environment undergoes fast and drastic shifts. Yet,
      perceptually our environment appears stable suggesting the existence of non
      retinotopic representations in addition to the well-known retinotopic ones. Here,
      we present a simple psychophysical test to determine whether a given visual
      process is accomplished in retino- or non-retinotopic coordinates. As examples,
      we show that visual search and motion perception can occur within a non
      retinotopic frame of reference. These findings suggest that more mechanisms than
      previously thought operate non-retinotopically. Whether this is true for a given
      visual process can easily be found out with our "litmus test."

PMID- 20055539
TI  - Spatiotemporally coherent motion direction perception occurs even for
      spatiotemporal reversal of motion sequence.
AB  - Thus far, it has been pointed out that motion representation is completed in
      motion trajectory, and that motion representation interferes with a single
      physical input at a specific time and space in the motion trajectory. However, it
      has not been fully investigated whether the internal motion representation could
      interact with multiple physical inputs across time and space in motion
      trajectory. Thus, the current research investigated whether spatiotemporally
      coherent motion perception could be established in a situation involving the
      spatiotemporal reversal of motion sequences. In a five-point motion display, we
      found that the motion direction perception of the last two stimuli containing the
      spatiotemporal reversal was consistent with three preceding stimuli. This failure
      to perceive motion direction reversal occurred when the shapes of motion
      trajectory (to upper or lower) were randomly changed. Moreover, we confirmed that
      one preceding stimulus (three-point motion) was sufficient to produce the failure
      to perceive motion direction reversal, and the effect of the prior stimuli
      saturated when the preceding sequence contained two or more stimuli. These
      findings suggest that the flexible internal motion representation mechanisms
      reorganize the spatiotemporal irregularities in motion trajectory and establish
      spatiotemporally coherent motion perceptions.

PMID- 20055540
TI  - Dynamic information for the recognition of conversational expressions.
AB  - Communication is critical for normal, everyday life. During a conversation,
      information is conveyed in a number of ways, including through body, head, and
      facial changes. While much research has examined these latter forms of
      communication, the majority of it has focused on static representations of a few,
      supposedly universal expressions. Normal conversations, however, contain a very
      wide variety of expressions and are rarely, if ever, static. Here, we report
      several experiments that show that expressions that use head, eye, and internal
      facial motion are recognized more easily and accurately than static versions of
      those expressions. Moreover, we demonstrate conclusively that this dynamic
      advantage is due to information that is only available over time, and that the
      temporal integration window for this information is at least 100 ms long.

PMID- 20055541
TI  - Motion-induced position shifts in global dynamic Gabor arrays.
AB  - Objects in motion appear shifted in space. For global motion stimuli we can ask
      whether the shift depends on the local or global motion. We constructed arrays of
      randomly oriented Gaussian enveloped drifting sine gratings (dynamic Gabors)
      whose speed was set such that the normal component of motion was consistent with
      a single global velocity. The array appears shifted in space in the direction of
      the global motion. The size of the shift is the same as for arrays of uniformly
      oriented dynamic Gabors that are moving in the same direction at the same global
      speed. Arrays made up of vertically oriented gratings whose speeds were set to
      the horizontal component of the random array elements were shifted less far. This
      shows that motion-induced position shifts of coherently moving surface patches
      are generated after the completion of the global motion computation.

PMID- 20055542
TI  - Where is the moving object now? Judgments of instantaneous position show poor
      temporal precision (SD = 70 ms).
AB  - Humans can precisely judge relative location between two objects moving with the
      same speed and direction, as numerous studies have shown. However, the precision
      for localizing a single moving object relative to stationary references remains a
      neglected topic. Here, subjects reported the perceived location of a moving
      object at the time of a cue. The variability of the reported positions increased
      steeply with the speed of the object, such that the distribution of responses
      corresponds to the distance that the object traveled in 70 ms. This surprisingly
      large temporal imprecision depends little on the characteristics of the
      trajectory of the moving object or of the cue that indicates when to judge the
      position. We propose that the imprecision reflects a difficulty in identifying
      which position of the moving object occurs at the same time as the cue. This high
      level process may involve the same low temporal resolution binding mechanism
      that, in other situations, pairs simultaneous features such as color and motion.

PMID- 20055543
TI  - Integration of monocular motion signals and the analysis of interocular velocity
      differences for the perception of motion-in-depth.
AB  - We investigated how the mechanism for perceiving motion-in-depth based on
      interocular velocity differences (IOVDs) integrates signals from the motion
      spatial frequency (SF) channels. We focused on the question whether this
      integration is implemented before or after the comparison of the velocity signals
      from the two eyes. We measured spatial frequency selectivity of the MAE of motion
      in depth (3D MAE). The 3D MAE showed little spatial frequency selectivity,
      whereas the 2D lateral MAE showed clear spatial frequency selectivity in the same
      condition. This indicates that the outputs of the monocular motion SF channels
      are combined before analyzing the IOVD. The presumption was confirmed by the
      disappearance of the 3D MAE after exposure to superimposed gratings with
      different spatial frequencies moving in opposite directions. The direction of the
      2D MAE depended on the test spatial frequency in the same condition. These
      results suggest that the IOVD is calculated at a relatively later stage of the
      motion analysis, and that some monocular information is preserved even after the
      integration of the motion SF channel outputs.

PMID- 20055544
TI  - Latitude and longitude vertical disparities.
AB  - The literature on vertical disparity is complicated by the fact that several
      different definitions of the term "vertical disparity" are in common use, often
      without a clear statement about which is intended or a widespread appreciation of
      the properties of the different definitions. Here, we examine two definitions of
      retinal vertical disparity: elevation-latitude and elevation-longitude
      disparities. Near the fixation point, these definitions become equivalent, but in
      general, they have quite different dependences on object distance and binocular
      eye posture, which have not previously been spelt out. We present analytical
      approximations for each type of vertical disparity, valid for more general
      conditions than previous derivations in the literature: we do not restrict
      ourselves to objects near the fixation point or near the plane of regard, and we
      allow for non-zero torsion, cyclovergence, and vertical misalignments of the
      eyes. We use these expressions to derive estimates of the latitude and longitude
      vertical disparities expected at each point in the visual field, averaged over
      all natural viewing. Finally, we present analytical expressions showing how
      binocular eye position-gaze direction, convergence, torsion, cyclovergence, and
      vertical misalignment-can be derived from the vertical disparity field and its
      derivatives at the fovea.

PMID- 20055545
TI  - The effect of changing size on vergence is mediated by changing disparity.
AB  - In this study, we investigated the effect of changing size on vergence. Erkelens
      and Regan (1986) proposed that this cue to motion in depth affects vergence in a
      similar way as it affects perception. The measured effect on vergence was small
      and we wondered why the vergence system would use changing size as an additional
      cue to changing disparity. To elucidate the effect of changing size on vergence,
      we used an annulus carrying both changing size and changing disparity signals to
      motion in depth. The cues were either congruent or signaled a different depth.
      The results showed that vergence was affected by changing size, however in an
      opposite way than that perception was affected. These results were incongruent
      with those reported by Erkelens and Regan (1986). We therefore additionally
      measured the effects on vergence of the individual parameters associated with
      changing size, i.e., stimulus area, retinal eccentricity, and luminance. Stimulus
      (retinal) eccentricity was inversely related to vergence gain. Luminance, on the
      other hand, had a smaller but positive relation to vergence gain. Thus, changing
      size affected the disparity signal two-fold: it changed the retinal location of
      the disparity signal and it changed the strength of the disparity signal
      (luminance change). These effects of changing size on disparity can explain both
      our results (change in retinal location of the disparity signal) and those of
      Erkelens and Regan (1986; change in luminance). We thus conclude that changing
      size did not in itself contribute to vergence, rather its effect on vergence was
      mediated by disparity.

PMID- 20055546
TI  - Edge detection and texture classification by cuttlefish.
AB  - Cephalopod mollusks including octopus and cuttlefish are adept at adaptive
      camouflage, varying their appearance to suit the surroundings. This behavior
      allows unique access into the vision of a non-human species because one can ask
      how these animals use spatial information to control their coloration pattern.
      There is particular interest in factors that affect the relative levels of
      expression of the Mottle and the Disruptive body patterns. Broadly speaking, the
      Mottle is displayed on continuous patterned surfaces whereas the Disruptive is
      used on discrete objects such as pebbles. Recent evidence from common cuttlefish,
      Sepia officinalis, suggests that multiple cues are relevant, including spatial
      scale, contrast, and depth. We analyze the body pattern responses of juvenile
      cuttlefish to a range of checkerboard stimuli. Our results suggest that the
      choice of camouflage pattern is consistent with a simple model of how cuttlefish
      classify visual textures, according to whether they are Uniform or patterned, and
      whether the pattern includes visual edges. In particular, cuttlefish appear to
      detect edges by sensing the relative spatial phases of two spatial frequency
      components (e.g., fundamental and the third harmonic Fourier component in a
      square wave). We discuss the relevance of these findings to vision and camouflage
      in aquatic environments.

PMID- 20055547
TI  - Catching fly balls in virtual reality: a critical test of the outfielder problem.
AB  - How does a baseball outfielder know where to run to catch a fly ball? The
      "outfielder problem" remains unresolved, and its solution would provide a window
      into the visual control of action. It may seem obvious that human action is based
      on an internal model of the physical world, such that the fielder predicts the
      landing point based on a mental model of the ball's trajectory (TP). However, two
      alternative theories, Optical Acceleration Cancellation (OAC) and Linear Optical
      Trajectory (LOT), propose that fielders are led to the right place at the right
      time by coupling their movements to visual information in a continuous "online"
      manner. All three theories predict successful catches and similar running paths.
      We provide a critical test by using virtual reality to perturb the vertical
      motion of the ball in mid-flight. The results confirm the predictions of OAC but
      are at odds with LOT and TP.

PMID- 20055549
TI  - The spatial scale of perceptual memory in ambiguous figure perception.
AB  - Ambiguous visual stimuli highlight the constructive nature of vision: perception
      alternates between two plausible interpretations of unchanging input. However,
      when a previously viewed ambiguous stimulus reappears, its earlier perception
      almost entirely determines the new interpretation; memory disambiguates the
      input. Here, we investigate the spatial properties of this perceptual memory,
      taking into account strong anisotropies in percept preference across the visual
      field. Countering previous findings, we show that perceptual memory is not
      confined to the location in which it was instilled. Rather, it spreads to
      noncontiguous regions of the visual field, falling off at larger distances.
      Furthermore, this spread of perceptual memory takes place in a frame of reference
      that is tied to the surface of the retina. These results place the neural locus
      of perceptual memory in retinotopically organized sensory cortical areas, with
      implications for the wider function of perceptual memory in facilitating stable
      vision in natural, dynamic environments.

PMID- 20055548
TI  - Chromatic and luminance contrast sensitivity in fullterm and preterm infants.
AB  - In order to investigate the contributions of visual experience vs. preprogrammed
      mechanisms on visual development, the current study compared contrast sensitivity
      in preterm vs. fullterm infants. If development is tied to time since conception,
      preterm infants should match the developmental trajectories of fullterm infants
      when plotted in postterm age. By contrast, if development is influenced by visual
      experience, preterm and fullterm infants should match when plotted in postnatal
      age. Luminance (light/dark) and chromatic (red/green) contrast sensitivities (CS)
      were measured in 25 preterm (born, on average, 6.6 weeks early) and 77 fullterm
      infants, between 1 and 6 months postterm. In the first few months, luminance CS
      was found to be predicted by postterm age, suggesting that preprogrammed
      development is sufficient to account for luminance CS. By contrast, chromatic CS
      exceeded that predicted by postterm age, which suggests that time since birth
      confers a benefit on chromatic CS. The preterms' 6.6 weeks of additional time
      since birth is roughly equivalent to 3.7 weeks of development in chromatic CS. In
      sum, these results suggest that chromatic CS is more influenced by early
      postnatal visual experience than luminance CS, which may have implications for
      development of parvocellular and magnocellular pathways.

PMID- 20055550
TI  - Optimal stimulus encoders for natural tasks.
AB  - Determining the features of natural stimuli that are most useful for specific
      natural tasks is critical for understanding perceptual systems. A new approach is
      described that involves finding the optimal encoder for the natural task of
      interest, given a relatively small population of noisy "neurons" between the
      encoder and decoder. The optimal encoder, which necessarily specifies the most
      useful features, is found by maximizing accuracy in the natural task, where the
      decoder is the Bayesian ideal observer operating on the population responses. The
      approach is illustrated for a patch identification task, where the goal is to
      identify patches of natural image, and for a foreground identification task,
      where the goal is to identify which side of a natural surface boundary belongs to
      the foreground object. The optimal features (receptive fields) are intuitive and
      perform well in the two tasks. The approach also provides insight into general
      principles of neural encoding and decoding.

PMID- 20055552
TI  - Pattern matching is assessed in retinotopic coordinates.
AB  - We typically examine scenes by performing multiple saccades to different objects
      of interest within the image. Therefore, an extra-retinotopic representation,
      invariant to the changes in the retinal image caused by eye movements, might be
      useful for high-level visual processing. We investigate here, using a matching
      task, whether the representation of complex natural images is retinotopic or
      screen-based. Subjects observed two simultaneously presented images, made a
      saccadic eye movement to a new fixation point, and viewed a third image. Their
      task was to judge whether the third image was identical to one of the two earlier
      images or different. Identical images could appear either in the same retinotopic
      position, in the same screen position, or in totally different locations.
      Performance was best when the identical images appeared in the same retinotopic
      position and worst when they appeared in the opposite hemifield. Counter to
      commonplace intuition, no advantage was conferred from presenting the identical
      images in the same screen position. This, together with performance sensitivity
      for image translation of a few degrees, suggests that image matching, which can
      often be judged without overall recognition of the scene, is mostly determined by
      neuronal activity in earlier brain areas containing a strictly retinotopic
      representation and small receptive fields.

PMID- 20055551
TI  - Top-down flow of visual spatial attention signals from parietal to occipital
      cortex.
AB  - Given the complexity of our visual environment, the ability to selectively attend
      to certain locations, while ignoring others, is crucial for reducing the amount
      of visual information to manageable levels and for optimizing behavioral
      performance. Sustained allocation of spatial attention causes persistent
      increases in functional magnetic resonance imaging (fMRI) signals in portions of
      early visual cortex that retinotopically represent the attended location, even in
      the absence of a visual stimulus. Here we test the hypothesis that
      topographically organized posterior parietal cortical areas IPS1 and IPS2
      transmit top-down spatial attention signals to early visual cortex. We employed
      fMRI and coherency analysis to measure functional connectivity among cortical
      areas V1, V2, V3, V3A, V3B, V7, IPS1, and IPS2 during sustained visual spatial
      attention. Attention increased the magnitude of coherency for many pairs of areas
      in occipital and parietal cortex. Additionally, attention-related activity in
      IPS1 and IPS2 led activity in several visual cortical areas by a few hundred
      milliseconds. These results are consistent with transmission of top-down spatial
      attention signals from IPS1 and IPS2 to early visual cortex.

PMID- 20055553
TI  - Effects of surrounding frame on visual search for vertical or tilted bars.
AB  - It is easier to find a tilted bar among vertical bars than vice-versa, but this
      asymmetry can be abolished or reversed by surrounding the bars with a tilted
      frame. The frame effect is important because it challenges bottom-up models of
      saliency. We conducted two experiments to investigate the causes of this effect.
      In Experiment 1, we removed different components of a square frame, and concluded
      that the frame effect was caused by a combination of (1) high-level configural
      cues that provided a frame of reference, and (2) bottom-up iso-orientation
      competition from the sides of the frame parallel to the bars. The iso-orientation
      competition could have arisen from (1) diversion of attention to the parts of the
      frame parallel to the target, or (2) iso-orientation suppression between nearby
      units selective for the same orientation. Experiment 2 investigated the nature of
      the iso-orientation competition process. In this experiment, we used a single
      line (the "axis") embedded in a circular field of bar elements, rather than a
      square frame surrounding them. The effect of the axis declined rapidly to zero
      with increasing target-axis distance, suggesting that the iso-orientation
      competition was caused entirely by iso-orientation suppression between nearby
      units tuned to the same orientation.

PMID- 20055554
TI  - The relationship between CA/C ratio and individual differences in dynamic
      accommodative responses while viewing stereoscopic images.
AB  - The oculomotor synergy as expressed by the CA/C and AC/A ratios was investigated
      to examine its influence on our previous observation that whereas convergence
      responses to stereoscopic images are generally stable, some individuals exhibit
      significant accommodative overshoot. Using a modified video refraction unit while
      viewing a stereoscopic LCD, accommodative and convergence responses to balanced
      and unbalanced vergence and focal stimuli (BVFS and UBVFS) were measured.
      Accommodative overshoot of at least 0.3 D was found in 3 out of 8 subjects for
      UBVFS. The accommodative response differential (RD) was taken to be the
      difference between the initial response and the subsequent mean static steady
      state response. Without overshoot, RD was quantified by finding the initial
      response component. A mean RD of 0.11 +/- 0.27 D was found for the 1.0 D step
      UBVFS condition. The mean RD for the BVFS was 0.00 +/- 0.17 D. There was a
      significant positive correlation between CA/C ratio and RD (r = +0.75, n = 8, p <
      0.05) for only UBVFS. We propose that inter-subject variation in RD is influenced
      by the CA/C ratio as follows: an initial convergence response, induced by
      disparity of the image, generates convergence-driven accommodation commensurate
      with the CA/C ratio; the associated transient defocus subsequently decays to a
      balanced position between defocus-induced and convergence-induced accommodations.

PMID- 20055557
TI  - Using traditional spirituality to reduce domestic violence within aboriginal
      communities.
AB  - OBJECTIVES: We report the results of involving traditional healing elders (THE)
      in the clinical care of aboriginal families who were involved in domestic
      violence in the context of a clinical case series of referrals made for domestic
      violence. METHODS: Psychiatric consultations were requested from senior author
      L.M.M. for 113 aboriginal individuals involved with domestic violence as
      recipients or perpetrators (or both) between July 2005 and October 2008. As part
      of their clinical care, all were encouraged to meet with a THE, with 69 agreeing
      to do so. The My Medical Outcomes Profile 2 scale was being used as a clinical
      instrument to document effectiveness. Elders used traditional cultural stories
      and aboriginal spirituality with individuals, couples, and families to transform
      the conditions underlying domestic violence. RESULTS: For those people who met
      with the THE, a statistically significant change (p < 0.0001) occurred in symptom
      severity from baseline to final interview of 4.6-1.52 on a scale of 0-6. The most
      common presenting symptom was being beaten (39 people), followed by drinking (37
      people), drugs (13 people), grudges and anger (12 people), sadness (9 people),
      hates self (8 people), fear (7 people), sleep problems (6 people), anxiety (5
      people), and lost spirituality (2 people). Each person chose two primary symptoms
      to rate. CONCLUSIONS: Including elders in the care of people who are the
      recipients of domestic violence is effective. We speculate that it helps by
      providing traditional stories about relationships and roles that do not include
      violence. Spiritual approaches within aboriginal communities may be more
      effective than more secular, clinical approaches. Research is indicated to
      compare elder-based interventions with conventional clinical care.

PMID- 20055558
TI  - Vipassana meditation: systematic review of current evidence.
AB  - OBJECTIVES: Vipassana meditation (VM) is one of the most ancient and diffused
      types of meditative practices belonging to the pole of mindfulness. Despite the
      growing interest toward the neurobiological and clinical correlates of many
      meditative practices, no review has specifically focused on current evidence on
      neuro-imaging and clinical evidence about VM. METHODS: A literature search was
      undertaken using MEDLINE,((R)) ISI web of knowledge, the Cochrane database, and
      references of retrieved articles. Controlled and cross-sectional studies with
      controls published in English up to March 2009 were included. RESULTS: Seven (7)
      mainly poor-quality studies were identified. Three (3) neuro-imaging studies
      suggested that VM practice could be associated with the activation of the
      prefrontal and the anterior cingulate cortex during meditative periods, and with
      increased thickness in cortical areas related to attention as well as increased
      subcortical gray matter in right insula and hippocampus in long-term meditators.
      Three (3) clinical studies in incarcerated populations suggested that VM could
      reduce alcohol and substance abuse but not post-traumatic stress disorder
      symptoms in prisoners. One (1) clinical study in healthy subjects suggested that
      VM could enhance more mature defenses and copying styles. DISCUSSION: Current
      studies provided preliminary results about neurobiological and clinical changes
      related to VM practice. Nonetheless, few and mainly low-quality data are
      available especially for clinical studies and current results have to be
      considered with caution. Further research is needed to answer critical questions
      about replications, self-selection, placebo, and long-term effects of VM.

PMID- 20055559
TI  - PEGylated PAMAM dendrimers as a potential drug delivery carrier: in vitro and in
      vivo comparative evaluation of covalently conjugated drug and noncovalent drug
      inclusion complex.
AB  - To understand more about the influence of the types of interaction between drug
      and PEGylated PAMAM dendrimers on the in vitro and in vivo behavior of drug,
      methotrexate (MTX) was coupled to PEGylated or non-PEGylated generation 4 PAMAM
      (G4) through complexing drug within the dendritic architecture and covalently
      conjugated onto the surface of the dendrimer, respectively. PAMAM was first
      modified with PEG(5000) chains at three different degrees of substitution. The
      ability of PEGylated G4 complexing MTX was higher than that of non-PEGylated one.
      MTX-G4 and MTX-G4-PEG conjugates were synthesized via amide linkages. MTX was
      readily released from all complexes in isotonic solution, while the conjugates
      hardly released MTX in the same medium and keep stable in human plasma and the
      lysosomal medium. There were no obvious differences between complexes and free
      MTX in cytotoxicity against KB cell line, whereas the conjugates showed the
      relatively low activity. In vivo study in rodents found that the MTX-G4-PEG
      conjugate exhibited significantly prolonged blood residence time and the
      strongest antitumor effects, as compared with MTX-G4, the complexes and MTX. The
      results indicated that the covalent attachment of drug to PEGylated PAMAM could
      be more effective for targeted drug delivery.

PMID- 20055560
TI  - Histopathological diagnosis of hydatidiform mole: contemporary features and
      clinical implications.
AB  - Gestational trophoblastic neoplasia (GTN) encompasses several entities including
      complete (CHM) and partial (PHM) hydatidiform mole (HM), malignant
      choriocarcinoma, and placental-site trophoblastic tumor. HMs are genetically
      abnormal, nonviable conceptions, which are associated with significantly
      increased risk for development of complications due to persistence of abnormal
      trophoblast (persistent GTN; pGTN), which occurs following 15% of CHM and 0.5% of
      PHM. Diagnostic histological features of HM are present in the first trimester
      but these features differ from those traditionally described in the later second
      trimester. The characteristic morphological findings of early HM include aspects
      of villous dysmorphism and abnormal villous trophoblast hyperplasia, with other
      specific features allowing reliable distinction between CHM and PHM. Optimal
      management of molar disease depends on its early histological identification and
      subsequent surveillance by measurement of maternal human chorionic gonoadotropin
      (hCG) for detection of pGTN based on rising or plateuing hCG levels such that
      early effective treatment is possible.

PMID- 20055561
TI  - Lewis A Barness annual lecture: juvenile diabetes revisited.
AB  - I am honored to have been asked to give this lecture to express our great
      appreciation for the major contributions of Dr. Lewis Barness to pediatric health
      care and the education of medical professionals that has improved the health and
      well-being of children. The previous Barness lecturers have been "out of town
      experts" whose careers had been significantly influenced by Dr. Barness. This
      year as you are well aware "the economy is very bad", so a local boy was chosen.
      I am very fortunate to have Dr. Barness as my mentor since I was a medical
      student and he has greatly influenced my career as well. I am much more
      pedestrian than the other invited lecturers, but I am pleased to have this
      opportunity to tell a little about the "Barness" impact on the development of
      this pediatric department.

PMID- 20055562
TI  - Current issues in the histopathology of gestational trophoblastic tumors.
AB  - Gestational trophoblastic neoplasia (GTN) encompasses several entities including
      complete (CHM) and partial (PHM) hydatidiform mole (HM) and the malignant
      gestational trophoblastic tumors (GTTs), choriocarcinoma (CC), and placental-site
      trophoblastic tumor (PSTT), including epithelioid trophoblastic tumor (ETT). To
      detect pGTN, postmolar surveillance by measurement of maternal human chorionic
      gonoadotropin (hCG) levels should be performed. With such a protocol, many cases
      of pGTN are identified early at a presymptomatic stage based on plateuing or
      rising hCG concentrations and subsequently treated successfully with
      chemotherapy. In such cases, histopathological confirmation of the precise nature
      of the pGTN usually is not available. However, GTT also may present clinically
      with primary or metastatic disease, either following and unrecognized HM or
      developing from a nonmolar gestation. Due to their distinctive clinical and
      histological features, malignant GTTs are generally clearly subdivided into CC
      and PSTT (including ETT). CC essentially represents malignant trophoblastic
      tumors with differentiation toward villous trophoblast, with extensive
      hematogenous spread and high hCG levels, which are highly chemoresponsive.
      However, PSTTs, represent malignant differentiation toward implantation-site type
      trophoblast, with lower hCG levels and less response to chemotherapy. Current
      issues regarding the clinical and histological features of CC and PSTT/ETT are
      discussed.

PMID- 20055563
TI  - Metastatic pulmonary adenocarcinoma to placenta and pleural fluid:
      clinicopathologic findings.
AB  - OBJECTIVES: To report the clinicopathologic findings of a pregnant woman with
      Stage IV adenocarcinoma of the lung with placental metastasis. MATERIALS AND
      METHODS: Medical records review. RESULTS: A 31-year-old G(2)P(1001) woman was
      diagnosed with Stage IV metastatic adenocarcinoma of the lung. At 34 weeks' and 2
      days' gestation, she went into preterm labor and delivered a live male infant,
      weighing 2595 grams, with Apgar scores of 9 and 9, respectively. Placental
      pathology was significant for adenocarcinoma with a solid and acinar pattern,
      consistent with that from the lung. Her postpartum course was uneventful. She did
      not receive chemotherapy and expired one month postpartum. To date, the infant is
      without evidence of disease. CONCLUSIONS: The occurance of lung cancer in
      pregnancy is rare and a few cases have been reported in literature. Placental
      metastasis is extremely uncommon in these cases and can lead to fetal involvement
      by lung tumor. It is important to report all cases of lung cancer occurring in
      pregnancy with subsequent close clinical surveillance of the infant as all cases
      have a different clinical picture.

PMID- 20055564
TI  - Spondyloepiphyseal dysplasia congenita.
AB  - We report a case of spondyloepiphyseal dysplasia congenita (SED congenita),
      diagnosed at autopsy of a term infant. Prenatal ultrasound at 20 weeks of
      gestation had shown shortening of all the fetal long bones, with bowing of the
      femora and humeri, clubfeet, and small thoracic cage. We discuss the diagnostic
      features of SED and the main differential diagnoses.

PMID- 20055565
TI  - Statistical methods in epidemiology. IX. Survival (failure-time) models.
AB  - PURPOSE: This article introduces readers to survival (failure-time) models, with
      a focus on Kaplan-Meier curves, Cox regression and sample size estimation.
      METHODS: An example is used to show readers how to calculate a Kaplan-Meier curve
      from first principles. RESULTS: What makes survival data unique is censoring.
      Readers should understand censoring before undertaking an analysis of survival
      data. CONCLUSION: The Cox model continues to set the standard for survival
      models, and will continue well into the future.

PMID- 20055566
TI  - Impact of caring for individuals with stroke on perceived physical health of
      informal caregivers.
AB  - PURPOSE: Caring for a person who has experienced stroke can be a formidable task
      placing considerable demands upon the informal caregiver. Although the impact of
      caring on mental health has been well established, less convincing associations
      between caregiving and declining physical health have been reported. In order to
      examine the impact of caregiving over time on the physical health of individuals
      providing informal care for individuals with stroke, we conducted a review of the
      published literature. METHOD: Literature searches of three electronic databases
      were conducted for the years 1996-2008 to identify studies providing longitudinal
      data based on repeated quantitative assessment of physical health. Pooled
      analyses were conducted. RESULTS: Sixteen studies were identified for inclusion.
      On the basis of pooled analyses, perceived physical health appeared stable over
      time. When comparisons to normative values were possible, the experience of
      health did not differ substantially from age- and sex-matched norms. Associations
      between physical health and psychological distress or well-being were identified.
      CONCLUSIONS: Informal caregiving does not result, necessarily, in reduced
      physical health. Further study is required to examine the timing and nature of
      the relationship between psychological distress and physical health to inform
      provision of services intended to maintain caregiver health and well being.

PMID- 20055567
TI  - Interventions for hemiplegic shoulder pain: systematic review of randomised
      controlled trials.
AB  - PURPOSE: The primary aim of this study was to assess the effectiveness of
      possible interventions for hemiplegic shoulder pain. The secondary aim was to
      investigate whether reduction of subluxation or spasticity can decrease shoulder
      pain and whether a change in shoulder pain is related to change in passive
      shoulder external rotation. METHOD: MEDLINE, EMBASE, CINAHL and the Cochrane
      Central Register of Controlled Trials databases were searched to obtain the
      randomised, controlled trials. Two authors independently extracted data and
      assessed the methodological quality of studies. RESULTS: Eight randomised trials
      were found in electronic databases. Aromatherapy plus acupressure, slow-stroke
      back massage and intramuscular neuromuscular electric stimulation were more
      effective than the controls at the end of treatment sessions. Intramuscular
      botulinum neurotoxin A injection and intraarticular triamcinolone acetonide
      injection were not helpful at one or three months after the end of treatment.
      Only intramuscular electric stimulation was effective at three months. These
      analyses found that shoulder pain improved independently of spasticity and
      subluxation. It was confirmed that the change in shoulder pain was associated
      with change in passive shoulder external rotation. CONCLUSIONS: Although five
      interventions were used for managing hemiplegic shoulder pain, their effects were
      limited in the context of trials.

PMID- 20055568
TI  - The role of pain for early rehabilitation in fast track total knee arthroplasty.
AB  - PURPOSE: To investigate the relationship between early functional mobility and
      pain intensity in a fast track program after total knee arthroplasty (TKA).
      METHODS: One hundred consecutive patients operated with TKA in an orthopaedic
      unit at a University hospital were prospectively studied. Measurements of
      independence in transfer and ambulation (Cumulated Ambulation Score), pain
      intensity (Verbal Analog Scale (VAS)), range of knee motion, functional mobility
      ('Timed Up & Go' (TUG) test), and walking distance were recorded daily from the
      first postoperative day until discharge. RESULTS: On the first postoperative day,
      90% of the patients were able to walk independently with median pain intensity of
      < or =5 on VAS. Of these, 78% walked > 70 m. All patients walked independently on
      postoperative Day 2 with pain intensity of < or =4. On the day of discharge, all
      patients walked with crutches with pain intensity of < or =3, walking distance >
      70 m, median range of motion 10-80 degrees , and median test time of the 'TUG'
      19.2 s. The length of hospital stay was median 3 days. CONCLUSION: Pain has a
      limited influence on the functional recovery beyond the first postoperative day
      after TKA, thereby allowing early physiotherapy.

PMID- 20055569
TI  - Controlled 3-year follow-up of a multidisciplinary pain rehabilitation program in
      primary health care.
AB  - PURPOSE: The high prevalence of musculoskeletal pain generates significant costs
      for primary health care and the whole of society. The development of appropriate
      interventions is therefore necessary. The aim of this effectiveness study was to
      assess the long-term effects of a primary health care multidisciplinary
      rehabilitation program in Sweden. METHODS: An experimental group comprising 89
      patients from two primary health care units received individualised treatment
      interventions after a multidisciplinary investigation. A control group of 69
      patients with the same inclusion criteria from four other primary health care
      units were treated according to routine. All participants completed
      questionnaires measuring pain, sick leave, quality of life, health care
      utilisation, drug consumption and psychosocial factors at baseline and at 3-year
      follow-up. RESULTS: After 3 years, utilisation of primary health care was
      significantly lower in the experimental group and work capacity was slightly but
      not significantly higher. The control group showed a trend of having a higher
      risk of high consumption after 3 years compared to the intervention group. There
      was no significant difference between the two groups concerning remaining
      variables such as function, catastrophising and pain. CONCLUSION: Both groups
      demonstrated considerable improvement over the course of 3 years. The
      experimental group had lower health care utilisation and a reduced risk of using
      large amounts of medication at the 3-year follow-up, indicating that compared
      with participants in the control group they were coping in a better way with
      pain.

PMID- 20055570
TI  - The relationship among frequency and type of internet use, perceived social
      support, and sense of well-being in individuals with visual impairments.
AB  - PURPOSE: To determine the relationship among amount and type of internet use and
      perceived social support and subjective well-being in persons with visual
      impairments. METHOD: One hundred seventy-five participants were recruited through
      a letter sent out over 46 national and state listservs for persons with visual
      impairments and blindness. The mean age of participants was 46.7 years (SD =
      13.3), and 50.9% were women. The participants completed a survey containing a
      demographic questionnaire, an internet use questionnaire, the personal resources
      questionnaire - 2000 (PRQ-2000), and the sense of well-being inventory (SWBI).
      RESULTS: Frequency and type of internet use was not significantly related to
      perceived social support in persons with visual impairments. There was a
      marginally significant positive association between internet use and overall
      sense of well-being. Specifically, online chat had a positive association with
      social support and well-being. Disability-related information seeking and
      participation in online support groups were negatively associated with well
      being. CONCLUSIONS: Despite the mixed results of this study, the internet has
      potential practical implications for increasing the independence and social
      connectedness in persons with visual impairments.

PMID- 20055571
TI  - The functional impact of a traumatic hand injury on people who live in rural and
      remote locations.
AB  - PURPOSE: This study aimed to gain an understanding of the functional impact of a
      traumatic hand injury on a rural and remote Australian population. METHOD: A
      retrospective, exploratory design was used. Patients who had experienced a
      traumatic hand injury were samples and were treated at the occupational therapy
      department at a major regional Australian hospital between January 2003 and
      February 2007 (n = 198). A mail-out survey was utilized, with 65 respondents
      included in the study. Questions focused on the impact on specific areas of
      occupational performance and on compliance to home exercises. The upper extremity
      functional index was also incorporated in the survey. RESULTS: The results
      revealed that almost 90% of survey respondents had residual difficulties as a
      result of the traumatic hand injury. The overall impact these difficulties have
      on 'day-to-day' life was moderate to extreme for over half of the respondents. In
      the areas of occupational performance, the most affected were work and leisure
      with less impact reported in self-care and rest. Comments were at times contrary
      with closed question data, with many respondents expressing relative satisfaction
      with their outcome despite highlighting the functional difficulties. CONCLUSION:
      A significant impact on occupational performance has been highlighted, which
      reflects common issues within this rural and remote population. Confirmation of
      the extent of these identified issues within the larger rural and remote
      Australian population will contribute to the formulation of policy and consequent
      improvements in health for this traditionally underserved population.

PMID- 20055572
TI  - Determining metabolic equivalent values of physical activities for persons with
      paraplegia.
AB  - PURPOSE: The compendium of physical activity (CPA) may not be appropriate for
      persons with paraplegia (PP) because of their possible low resting metabolic rate
      (RMR), or 1 MET, and a lack of physical activities (PAs) engaged by PP in the
      CPA. A CPA supplement, therefore, is needed. The purpose of this study was to
      examine the feasibility of constructing a short supplement for PP with two
      specific aims: to determine whether PP need an alternative 1-MET value and if
      selected PA can be classified into corresponding categories based on their
      'engagement' and 'energy expenditure (EE)' characteristics. METHOD: Thirty-one PP
      (161.26 cm +/- 22.99 cm, 60.52 kg +/- 15.32 kg, and 24.16 +/- 6.25 years) were
      recruited. RMR and 10 PA with different intensities were measured using indirect
      calorimetry. The z- and t-tests were employed to examine MET difference between
      the measured values and those of CPA (alpha = 0.05). RESULTS: One-MET for PP (3.1
      mL/kg/min) was lower than that of the CPA (3.5 mL/kg/min). Although some MET
      values were found to be similar to those in the CPA, others were statistically
      significantly different. CONCLUSIONS: To be able to measure PA-related EE of a
      disability subpopulation using the CPA accurately, a supplement that accounts for
      the impact of different types of activities and the EE characteristics of the
      subpopulation must be developed.

PMID- 20055573
TI  - Course of health-related quality of life in 9-16-year-old children with cerebral
      palsy: associations with gross motor abilities and mental health.
AB  - PURPOSE: To chart the 3-year course of health-related quality of life (HRQoL) of
      9--13-year-old children with cerebral palsy (CP), and to determine its
      relationship with gross motor abilities and mental health. METHODS: Children (n =
      91; 58 boys, mean age 11 years, age ranging from 8 years and 6 months to 13 years
      and 8 months) and parents were assessed annually with the TNO-AZL questionnaires
      for children's health-related quality of life as a dependent variable, and the
      gross motor function measure for children with CP and the child behaviour check
      list as independent variables. RESULTS: The children reported lower HRQoL
      compared with children in the general population, but reported a higher HRQoL
      than their parents. The HRQoL remained fairly stable over the 3 years, except for
      an increase in the autonomy domain. The HRQOL was moderately associated with
      gross motor abilities, and negatively associated with internalising mental health
      problems. Externalising problems were only negatively associated with parent
      reported HRQoL. CONCLUSIONS: Children with CP are more resilient and positive
      about their HRQoL than their parents think they are. In general, mental health in
      children with CP appeared to be important in understanding their perceived QoL,
      in addition to the severity of the CP itself.

PMID- 20055574
TI  - Osteomyelitis of the iliac crest: a rare complication following perforated
      appendicitis.
AB  - BACKGROUND: Appendicitis is a common surgical emergency with numerous
      postoperative infective complications. We report an unusual case of iliac crest
      osteomyelitis as a late complication following emergency appendectomy for
      perforated gangrenous appendicitis. METHODS: Review of the pertinent English
      language literature. RESULTS: To the best of our knowledge, this is the first
      report in the English literature to describe iliac crest osteomyelitis as an
      infective complication of perforated gangrenous appendicitis. The diagnosis was
      made with the aid of magnetic resonance imaging and radioisotope bone scans. The
      complication was treated successfully with broad-spectrum intravenous antibiotics
      and physiotherapy. CONCLUSION: Iliac crest osteomyelitis is indeed a rare
      complication of appendicitis. A heightened awareness and better understanding of
      this complication would necessitate early diagnosis and treatment.

PMID- 20055576
TI  - Circulation of group 2 coronaviruses in a bat species common to urban areas in
      Western Europe.
AB  - Fecal samples of 211 bats representing 13 different bat species from 31 locations
      in the Netherlands were analyzed for the presence of coronaviruses (CoV) using a
      genus-wide reverse transcription (RT)-polymerase chain reaction. CoVs are known
      for their high potential for interspecies transmission, including zoonotic
      transmission with bats as reservoir hosts. For the first time, a group 2 CoV was
      found in a bat, Pipistrellus pipistrellus, in Europe. This is of particular
      interest for public health as the reservoir host is a species that is common to
      urban areas in most of Europe and notorious for its close interactions with
      humans. Four verspertilionid bat species were found to excrete group 1 CoVs, viz.
      Myotis daubentonii, M. dasycneme, P. pipistrellus, and Nyctalus noctula. The last
      species is a newly identified reservoir. The overall prevalence was 16.9% and
      positive bats were found at multiple widespread locations. The circulating group
      1 CoV lineages were rather species associated than location associated.

PMID- 20055577
TI  - Corynebacterium ulcerans isolated from an asymptomatic dog kept in an animal
      shelter in the metropolitan area of Rio de Janeiro, Brazil.
AB  - Corynebacterium ulcerans was isolated from nares of one asymptomatic dog kept in
      an animal shelter in the metropolitan area of Rio de Janeiro, Brazil. The RNA
      polymerase beta subunit-encoding gene was sequenced to confirm the species
      identity. C. ulcerans strains producing phospholipase D, but not diphtheria
      toxin, are able to cause severe disease in humans, such as pneumonia and
      granulomatous nodules in pulmonary tissues. The infection rate varies really
      widely by region, probably because of the variations in the reported infection
      rates. Dogs with unapparent C. ulcerans infections may be considered as
      potentially capable of infecting other animals and humans, including pet owners.
      Medical and veterinary staff should be aware that asymptomatic animals can carry
      C. ulcerans and cooperate in eliminating infections and monitoring animals also
      in the developing countries.

PMID- 20055578
TI  - Natural host relationships of hantaviruses native to western Venezuela.
AB  - Strains of Cano Delgadito virus (CADV) and Maporal virus (MAPV) were isolated
      from 25 (8.9%) of the 280 rodents captured on farms in 1997 in western Venezuela.
      The results of analyses of laboratory and zoographic data indicated that Alston's
      cotton rat (Sigmodon alstoni) is the principal host of CADV, horizontal virus
      transmission is the dominant mode of CADV transmission in Alston's cotton rat in
      nature, a pygmy rice rat (Oligoryzomys sp.) is the principal host of MAPV, and
      the natural host relationships of CADV and MAPV are highly specific.

PMID- 20055580
TI  - Molecular detection of hemoprotozoa and Rickettsia species in arthropods
      collected from wild animals in the Burgos Province, Spain.
AB  - Limited information on the presence of bacterial and hematozoan infections in
      parasitic arthropods from Spain is available. In an attempt to address this
      issue, the prevalence of Theileria, Babesia, Hepatozoon, and Rickettsia species
      was investigated by polymerase chain reaction plus sequencing. In a survey for
      zoonotic pathogens in ectoparasites, 42 wild animals (which included rodents,
      carnivores, Sciuridae, and Cervidae) were captured in Burgos (Spain). A total of
      256 arthropods (including 107 ticks, 76 fleas, and 73 mites) were collected from
      these mammals. Molecular diagnostic results showed that (i) Rickettsia felis was
      found in fleas (two Ctenocephalides felis), (ii) Hepatozoon sp. infected some
      fleas (two Ctenophtalmus sp. and a DNA pool of Ceratophyllus sciurorum) and Acari
      (one Neotrombicula sp.), and (iii) Theileria annae was found in Ixodes ricinus
      and I. hexagonus (each a single infected specimen). All microorganisms and
      parasites were genetically identical to pathogens already described in Spain or
      elsewhere. Infected arthropods were recovered from beech marten, bank vole,
      squirrel, wood mouse, and red fox. Our findings emphasize the potential risk for
      transmission of rickettsias to humans (namely, R. felis) in Burgos, since C.
      felis is capable to seek out humans for feeding. No hemoprotozoa with proven
      significance as human pathogens were found in the survey. However, finding T.
      annae in ticks recovered from wild canids suggests possible links of sylvatic and
      domestic cycles for some Piroplasmida.

PMID- 20055581
TI  - Pedilanthus tithymaloides (Euphorbiaceae) leaf extract phytochemicals: toxicity
      to the filariasis vector Culex quinquefasciatus (Diptera: Culicidae).
AB  - An ethanolic extract of Pedilanthus tithymaloides L. (Euphorbiaceae) leaves was
      tested for biological activity against the eggs, larvae, and pupae of Culex
      quinquefasciatus. Significant mortality effects were observed in each life stage.
      In eggs, these effects ranged from 7% to 14% at the 0.013-0.040% concentrations,
      respectively. In larvae, the same concentration range induced, respectively, 30
      95% and 23-88% mortality in first to fourth instars. In pupae, 0.013-0.040%
      concentrations of leaf extract induced between 18% and 42% mortality. Fitted
      probit-mortality curves for larvae indicated the median and 90% lethal
      concentrations (LC(50)/LC(90)) of extract for instars 1-4 to be 0.024/0.042,
      0.025/0.043, 0.026/0.045, and 0.028/0.047, respectively. Qualitative analyses of
      the extract revealed the presence of flavonoids, phenols, and steroids but the
      absence of alkaloids, glycosides, resins, saponins, and tannins. The results
      indicate that Pe. tithymaloides leaf extract exhibits significant biological
      activity against immature stages of Cx. quinquefasciatus and warrants further
      study for development and use as a natural product-based biocide in disease
      vector control.

PMID- 20055582
TI  - Identification of in vivo-induced conserved sequences from Yersinia pestis during
      experimental plague infection in the rabbit.
AB  - In an effort to identify the novel virulence determinants of Yersinia pestis, we
      applied the gene "discovery" methodology, in vivo-induced (IVI) antigen
      technology, to detect genes upregulated during infection in a laboratory rabbit
      model for bubonic plague. After screening over 70,000 Escherichia coli clones of
      Y. pestis DNA expression libraries, products from 25 loci were identified as
      being seroreactive to reductively adsorbed, pooled immune serum. Upon sequence
      analysis of the predicted IVI gene products, more frequently encountered
      conserved protein functional categories have emerged, to include type-V
      autotransporters and components of more complex secretion systems including types
      III and VI. The recombinant products from eight selected clones were subsequently
      immunoblotted against pooled immune serum from two naturally infected host
      species: the prairie dog, and a species refractory to lethal disease, the coyote.
      Immune prairie dog serum recognized 2-3 of the rabbit-reactive antigens,
      suggesting at least some overlap in the pathogen's in vivo survival mechanisms
      between these two hosts. Although the coyote serum failed to recognize most of
      the IVI antigens, LepA was universally reactive with all three host sera.
      Collectively, the profiles/patterns of IVI conserved sequences (IVICS) may
      represent immune "signatures" among different host species, possessing the
      potential for use as a diagnostic tool for plague. Further, the antigenic nature
      of IVICS makes them ideal for further evaluation as novel subunit vaccine
      candidates. The gathering of additional data and analysis of the intact IVI genes
      and the expressed IVICS products should provide insight into the unique biologic
      processes of Y. pestis during infection and reveal the genetic patterns of the
      pathogen's survival strategy in different hosts.

PMID- 20055585
TI  - Responsibilities and innovation.

PMID- 20055586
TI  - Short communication: Simultaneous substitutions of V38M and N43T-N44K in the gp41
      heptad repeat 1 (HR1) disrupt HIV type 1 gPr160 endoproteolytic cleavage (*).
AB  - We cloned and sequenced gp41 HIV-1 from plasma of AIDS patients under HAART and T
      20 (enfuvirtide, Fuzeon) therapy and revealed several T-20 resistance-associated
      mutations. Two mutations, a single V38A and a double N43T-N44K were the most
      frequent; however, they were not found together in one clone. We anticipated that
      simultaneous mutations of these three residues might play a vital role in the
      viral life cycle. To address this problem, we introduced N43T-N44K and V38M +
      N43T-N44K substitutions to a cloned gp41 and introduced modified gp41 into the
      pNL4-3 molecular clone. HEK293T cells were transfected with the obtained vectors
      and released viruses were examined for reverse transcriptase (RT) activity,
      infectivity on reporter TZM-bl cells, and in Western blotting. Nearly equal RT
      activity was demonstrated in viruses with and without mutations. However, viruses
      with the V38M + N43T-N44K mutations were not infectious and, as shown by Western
      blotting, gPr160 cleavage was impaired. These data suggest that V38M + N43T-N44K
      mutations perturbed the natural conformation of gPr160 in a way that access of
      furin to the cleavage site (REKR) was blocked. Therefore, the residues V38 + N43
      N44 retain the gPr160 conformation in proximity to the furin cleavage site and,
      as a consequence, are critical for virus infectivity. These data may explain why
      viruses with V38M + N43T-N44K mutations were not previously detected in the
      plasma of T-20-experienced patients.

PMID- 20055587
TI  - Transmitted HIV Type 1 drug resistance and Non-B subtypes prevalence among
      seroconverters and newly diagnosed patients from 1992 to 2005 in Italy.
AB  - The patterns of transmitted drug-resistant (TDR) HIV-1 variants, non-B subtype
      spread, and epidemiological trends were evaluated either in seroconverters or in
      newly diagnosed individuals in Italy over a 13-year period. We analyzed 119
      seroconverters, enrolled from 1992 to 2003 for the CASCADE study, and 271 newly
      diagnosed individuals of the SPREAD study (2002-2005), of whom 42 had a known
      seroconversion date. Overall, TDR was 15.1% in the CASCADE and 12.2% in the
      SPREAD study. In the 1992-2003 period, men having sex with men (MSMs) and
      heterosexuals (HEs) were 48.7% and 36.8%, respectively; TDR was found to be
      higher in MSMs compared to HEs (78.9% vs. 21%, p = 0.006). The same groups were
      39.1% and 53.3% in the SPREAD study; however, no association was detected between
      modality of infection and TDR. Overall, 9.2% and 22.1% of individuals harbored a
      non-B clade virus in the CASCADE and SPREAD study, respectively. As evidence of
      onward transmission, 40% (24/60) of non-B variants were carried by European
      individuals in the latter study; among these patients the F1 subtype was highly
      prevalent (p = 0.00001). One of every eight patients who received a diagnosis of
      HIV-1 in recent years harbored a resistant variant, reinforcing the arguments for
      baseline resistance testing to customize first-line therapy in newly infected
      individuals. The spread of non-B clades may act as a dilution factor of TDR
      concealing the proportion of TDR in seroconverters and MSMs.

PMID- 20055588
TI  - Can we treat our way out of HIV?
AB  - There is a range of settings in which antiretroviral therapy can decrease the
      incidence of HIV. Recently, it was revealed that the National Institutes of
      Health (NIH) and the Centers for Disease Control and Prevention (CDC) plan to
      study a test and treat strategy to reduce the spread of HIV. A test and treat
      strategy presents numerous implementation, operational, structural, and policy
      issues that will require research to be effectively addressed. The timing of the
      interest in a test and treat strategy and this first foray into exploring its
      potential implementation come at a critical juncture in the history of HIV/AIDS
      in the United States, where recent data from the CDC indicate that the prevalence
      and incidence of HIV are considerably higher than had previously been thought,
      and the Obama administration is currently developing a National HIV/AIDS Strategy
      (NHAS) whose three primary goals are reducing HIV incidence, increasing access to
      care, and reducing HIV-related health disparities. Indeed, the test and treat
      strategy is possibly unique in its direct relevance to all three main goals of
      the NHAS. A strategic approach to research will define portfolios and allocate
      resources based on their ability to move toward accomplishing the three NHAS
      goals. A National HIV/AIDS Strategy that both informs and is informed by a strong
      research agenda is a long-awaited and much anticipated development in the battle
      against HIV/AIDS in the United States.

PMID- 20055590
TI  - Genetic diversity on the integrase region of the pol gene among HIV type 1
      infected patients naive for integrase inhibitors in Sao Paulo City, Brazil.
AB  - The presence of mutations associated with integrase inhibitor (INI) resistance
      among INI-naive patients may play an important clinical role in the use of those
      drugs Samples from 76 HIV-1-infected subjects naive to INIs were submitted to
      direct sequencing. No differences were found between naive (25%) subjects and
      subjects on HAART (75%). No primary mutation associated with raltegravir or
      elvitegravir resistance was found. However, 78% of sequences showed at least one
      accessory mutation associated with resistance. The analysis of the 76 IN
      sequences showed a high polymorphic level on this region among Brazilian HIV-1
      infected subjects, including a high prevalence of aa substitutions related to INI
      resistance. The impact of these findings remains unclear and further studies are
      necessary to address these questions.

PMID- 20055593
TI  - HIV type 1 molecular epidemiology among high-risk clients attending the Thai Red
      Cross Anonymous Clinic in Bangkok, Thailand.
AB  - Several studies have reported an increasing number of non-CRF01_AE infections in
      high-risk groups in Thailand suggesting a more complex HIV-1 epidemic. This study
      assessed the complexity of the HIV epidemic among high-risk clients tested for
      HIV-1 at the Thai Red Cross Anonymous Clinic (TRCAC) between July 1, 2006 and
      February 28, 2007. HIV-1 genotypes were determined from plasma of infected
      subjects (n = 401) by the multiregion hybridization assay (MHAbce, v.2).
      Univariate and multivariate logistic regression analyses were used to determine
      risk factors associated with HIV prevalence and non-CRF01_AE infection. The
      estimated overall HIV prevalence was 14.1%: 25.3% among men who have sex with men
      (MSM), 18.4% among heterosexual women, and 9.6% among heterosexual men. Among the
      risk factors found to be associated with HIV prevalence were age (25-29 years),
      risk behavior (MSM), marital status (not single), education (less than high
      school), and inconsistent condom use. Overall, non-CRF01_AE strains accounted for
      18.9% of the infections: 25.3% among MSM and 14.8% and 20.4% among heterosexual
      women and men, respectively. Our results indicate a concentrated and genetically
      complex HIV epidemic among Thai MSM. These findings advocate for targeted
      intervention and prevention measures among high-risk populations in Thailand.

PMID- 20055596
TI  - Biological monitoring of wood-smoke exposure.
AB  - It has been clearly established that exposure to wood smoke is associated with a
      variety of adverse health effects in humans. However, we still have much to learn
      about the relationship between wood-smoke exposure and disease, including
      determination of what should be considered a "safe" level of exposure, and
      whether wood smoke should be regulated separately from other sources of air
      pollution. To help answer these questions, improved measures of exposure in
      populations exposed to wood smoke are required. In this mini-review we discuss
      how biomarkers of exposure can be used to complement the current suite of methods
      used to assess wood-smoke exposures. We critically review the compounds that are
      currently being evaluated as biomarkers of exposure to wood smoke, and we
      identify the strengths and weaknesses of these compounds. We find that, in
      general, these compounds show promise in situations where wood-smoke exposures
      are high, but where exposures are low non-wood-smoke sources are likely to be the
      major determinants of biomarker levels. We also outline a research framework that
      will move this field forward and maximize the potential for wood-smoke biomarkers
      to add value to epidemiological studies of wood-smoke health effects.

PMID- 20055594
TI  - HIV type 1 from a patient with baseline resistance to CCR5 antagonists uses drug
      bound receptor for entry.
AB  - CCR5 antagonists are a new class of antiretroviral drugs that block viral entry
      by disrupting interactions between the viral envelope (Env) glycoprotein and
      coreceptor. During the CCR100136 (EPIC) Phase IIb study of the CCR5 antagonist
      aplaviroc (APL) in treatment-naive individuals, a patient was identified who
      harbored virus strains that exhibited partial resistance to APL at the time of
      virologic failure. Retrospectively, it was found that APL resistance was present
      at baseline as well. To investigate the mechanism of APL resistance in this
      patient, we cloned HIV-1 env genes from plasma obtained at baseline and after
      virologic failure. Approximately 85% of cloned Envs were functional, and all
      exhibited partial resistance to APL. All Envs were R5-tropic, were partially
      resistant to other CCR5 antagonists including maraviroc on cells with high CCR5
      expression, but remained sensitive to the fusion inhibitor enfuvirtide.
      Competition studies with natural CCR5 ligands revealed that the mechanism of drug
      resistance entailed the use of the drug-bound conformation of CCR5 by the Env
      proteins obtained from this individual. The degree of drug resistance varied
      between Env clones, and also varied depending on the cell line used or the donor
      from whom the primary T cells were obtained. Thus, both virus and host factors
      contribute to CCR5 antagonist resistance. This study shows that R5 HIV-1 strains
      resistant to CCR5 inhibitors can arise in patients, confirming a mechanism of
      resistance previously characterized in vitro. In addition, some patients can
      harbor CCR5 antagonist-resistant viruses prior to treatment, which may have
      implications for the clinical use of this new class of antiretrovirals.

PMID- 20055602
TI  - Undifferentiated high-grade pleomorphic sarcomas in children: a clinicopathologic
      study of 10 cases and review of literature.
AB  - Undifferentiated high-grade pleomorphic sarcoma (UHGPS) is a sarcoma of debated
      nosology affecting adults, with rare cases reported in children. In order to
      investigate the clinicopathologic and prognostic features of pediatric UHGPS, 10
      cases of UHGPS occurring before 18 years (mean age, 8.9 years) were analyzed. All
      were localized at diagnosis (head, 4; lower extremities, 4; trunk, 2), with a
      mean diameter of 4.5 cm. Mean follow-up was 6 years. Six patients were in
      complete remission, 1 after a relapse; 2 died of metastatic disease; 1 was alive
      with metastasis. Histologically, 8 tumors showed spindle cells with a focal or
      diffuse storiform pattern; 2 tumors had scattered aggregates of epithelioid
      cells. Two tumors displayed a prominent epithelioid component. Cellular
      pleomorphism, high mitotic rate with atypical mitoses, were found in all tumors;
      necrosis in 6 and vascular invasion in 2. CD68 and desmin were positive in 2
      cases each, smooth muscle actin in 4, and S100 in 1. Five tumors in 1st and 1 in
      2nd complete remission were superficial; 1 showed a spindle cell morphology with
      epithelioid foci, 3 had necrosis; 5 were grade 3; and 1 was grade 2. Three
      metastatic tumors (2 in the dura, 1 in the leg) displayed either a prominent
      epithelioid morphology (2) or scattered aggregates of epithelioid cells (1), with
      a myxoid background in 1. All were grade 3 and showed foci of necrosis. In
      summary, UHGPS is rare in children and frequently located in the head. A more
      favorable outcome is associated with superficial location. Foci of epithelioid
      cell may portend an aggressive behavior.

PMID- 20055632
TI  - The changes in hazard classification and product notification procedures of the
      new European CLP and Cosmetics Regulations.
AB  - INTRODUCTION: The United Nations Globally Harmonized System of Classification and
      Labelling of Chemicals (UN-GHS) is developed to harmonize the criteria for hazard
      communication worldwide. The European Regulation on classification, labeling, and
      packaging of substances and mixtures [CLP Regulation (European Commission, EC) No
      1272/2008] will align the existing European Union (EU) legislation to the UN-GHS.
      This CLP Regulation entered into force on January 20, 2009, and will, after a
      transitional period, replace the current rules on classification, labeling, and
      packaging for supply and use in Europe. Both old and new classifications will
      exist simultaneously until 2010 for substances and until 2015 for mixtures.
      HAZARD CLASSIFICATION: The new hazard classification will introduce new health
      hazard classes and categories, with associated new hazard pictograms, signal
      words, Hazard (H)-statements, and Precautionary (P)-statements as labeling
      elements. Furthermore, the CLP Regulation will affect the notification of product
      information on hazardous products to poisons information centers (PICs). PRODUCT
      NOTIFICATION PROCEDURES: At this moment product notification widely varies in
      procedures and requirements across EU Member States. Article 45 of the CLP
      Regulation contains a provision stating that the EC will (by January 20, 2012)
      review the possibility of harmonizing product notification. The European
      Association of Poisons Centres and Clinical Toxicologists (EAPCCT) is recognized
      as an important stakeholder. For cosmetic products, the new Cosmetics Regulation
      will directly implement a new procedure for electronic cosmetic product
      notification in all EU Member States. CONCLUSION: Both the CLP Regulation and the
      Cosmetics Regulation will develop their own product notification procedure within
      different time frames. Harmonization of notification procedures for both product
      groups, especially a common electronic format, would be most effective from a
      cost-benefit viewpoint and would be welcomed by PICs.

PMID- 20055633
TI  - Fatal human poisoning with Padan: a cartap-containing pesticide.
AB  - We report a patient who ingested about 13 g of Padan SG, a cartap-containing
      pesticide. After ingestion, the patient developed multiple seizures and dyspnea
      and lost consciousness. The patient did not recover and died on the fifth
      hospital day despite treatment at the early stage of poisoning. The cause of
      death was multisystem organ failure. Results of toxicological analysis were as
      follows: concentrations of nereistoxin (cartap metabolite) were 10.6 microg/mL in
      plasma, 18.2 microg/mL in urine, and 2.6 mg/mL in gastric fluid. Results of drug
      screening of urine by Triage DOA Panels and using an organophosphate detection
      kit were negative.

PMID- 20055640
TI  - Guideline for disinfection and sterilization of prion-contaminated medical
      instruments.

PMID- 20055641
TI  - Can skin marker pens, used preoperatively to prevent wrong-site surgeries,
      transfer bacteria?

PMID- 20055642
TI  - Watching them wash: description of a hand hygiene observation program.

PMID- 20055643
TI  - Infection prevention education: are we neglecting it?

PMID- 20055645
TI  - Role of the host-selective ACT-toxin synthesis gene ACTTS2 encoding an enoyl
      reductase in pathogenicity of the tangerine pathotype of Alternaria alternata.
AB  - ABSTRACT The tangerine pathotype of Alternaria alternata produces host-selective
      ACT-toxin and causes Alternaria brown spot disease of tangerines and tangerine
      hybrids. Sequence analysis of a genomic BAC clone identified a previously
      uncharacterized portion of the ACT-toxin biosynthesis gene cluster (ACTT). A
      1,034-bp gene encoding a putative enoyl-reductase was identified by using rapid
      amplification of cDNA ends and polymerase chain reaction and designated ACTTS2.
      Genomic Southern blots demonstrated that ACTTS2 is present only in ACT-toxin
      producers and is carried on a 1.9 Mb conditionally dispensable chromosome by the
      tangerine pathotype. Targeted gene disruption of ACTTS2 led to a reduction in ACT
      toxin production and pathogenicity, and transcriptional knockdown of ACTTS2 using
      RNA silencing resulted in complete loss of ACT-toxin production and
      pathogenicity. These results indicate that ACTTS2 is an essential gene for ACT
      toxin biosynthesis in the tangerine pathotype of A. alternata and is required for
      pathogenicity of this fungus.

PMID- 20055646
TI  - Breakdown of host resistance by independent evolutionary lineages of Beet
      necrotic yellow vein virus involves a parallel c/u mutation in its p25 gene.
AB  - ABSTRACT Breakdown of sugar beet Rz1-mediated resistance against Beet necrotic
      yellow vein virus (BNYVV) infection was previously found, by reverse genetics, to
      be caused by a single mutation in its p25 gene. The possibility of alternative
      breaking mutations, however, has not been discarded. To explore the natural
      diversity of BNYVV in the field and its effects on overcoming Rz1, wild-type (WT)
      and resistance-breaking (RB) p25 genes from diverse production regions of North
      America were characterized. The relative titer of WT p25 was inversely correlated
      with disease expression in Rz1 plants from Minnesota and California. In
      Minnesota, the predominant WT p25 encoded the A(67)C(68) amino acid signature
      whereas, in California, it encoded A(67)L(68). In both locations, these WT
      signatures were associated with asymptomatic BNYVV infections of Rz1 cultivars.
      Further analyses of symptomatic resistant plants revealed that, in Minnesota, WT
      A(67)C(68) was replaced by V(67)C(68) whereas, in California, WT A(67)L(68) was
      replaced by V(67)L(68). Therefore, V(67) was apparently critical in overcoming
      Rz1 in both pathosystems. The greater genetic distances between isolates from
      different geographic regions rather than between WT and RB from the same location
      indicate that the underlying C to U transition originated independently in both
      BNYVV lineages.

PMID- 20055647
TI  - Systemic colonization of potato plants by a soilborne, green fluorescent protein
      tagged strain of Dickeya sp. biovar 3.
AB  - ABSTRACT Colonization of potato plants by soilborne, green fluorescent protein
      (GFP)-tagged Dickeya sp. IPO2254 was investigated by selective plating,
      epifluorescence stereo microscopy (ESM), and confocal laser scanning microscopy
      (CLSM). Replicated experiments were carried out in a greenhouse using plants with
      an intact root system and plants from which ca. 30% of the lateral roots was
      removed. One day after soil inoculation, adherence of the pathogen on the roots
      and the internal colonization of the plants were detected using ESM and CLSM of
      plant parts embedded in an agar medium. Fifteen days post-soil inoculation,
      Dickeya sp. was found on average inside 42% of the roots, 13% of the stems, and
      13% of the stolons in plants with undamaged roots. At the same time-point, in
      plants with damaged roots, Dickeya sp. was found inside 50% of the roots, 25% of
      the stems, and 25% of the stolons. Thirty days postinoculation, some plants
      showed true blackleg symptoms. In roots, Dickeya sp. was detected in parenchyma
      cells of the cortex, both inter- and intracellularly. In stems, bacteria were
      found in xylem vessels and in protoxylem cells. Microscopical observations were
      confirmed by dilution spread-plating the plant extracts onto agar medium directly
      after harvest. The implications of infection from soilborne inoculum are
      discussed.

PMID- 20055648
TI  - Rapid detection of Phytophthora ramorum and P. kernoviae by two-minute DNA
      extraction followed by isothermal amplification and amplicon detection by generic
      lateral flow device.
AB  - ABSTRACT A method for nucleic-acid-based detection of pathogens in plant material
      has been developed which comprises a simple and rapid method for extracting DNA
      on the nitrocellulose membranes of lateral-flow devices, loop-mediated isothermal
      amplification (LAMP) of target DNA using labeled primers, and detection of the
      generically labeled amplification products by a sandwich immunoassay in a lateral
      flow-device format. Each of these steps can be performed without specialist
      equipment and is suitable for on-site use, and a result can be obtained in just
      over an hour. A LAMP assay for the detection of plant DNA (cytochrome oxidase
      gene) can be used in conjunction with pathogen-specific assays to confirm
      negative results. The use of this method is demonstrated for the detection of
      Phytophthora ramorum, the causal agent of sudden oak death and dieback/leaf
      blight in a range of tree, shrub, and herbaceous species, and the recently
      described pathogen P. kernoviae.

PMID- 20055649
TI  - Variation in competitive ability among isolates of Aspergillus flavus from
      different vegetative compatibility groups during maize infection.
AB  - ABSTRACT Aspergillus flavus, the primary causal agent of aflatoxin contamination,
      includes many genetically diverse vegetative compatibility groups (VCGs).
      Competitive ability during infection of living maize kernels was quantified for
      isolates from 38 VCGs. Kernels were inoculated with both a common VCG, CG136, and
      another VCG; after 7 days (31 degrees C), conidia were washed from kernels, and
      aflatoxins and DNA were extracted from kernels and conidia separately. CG136
      specific single-nucleotide polymorphisms were quantified by pyrosequencing; VCGs
      co-inoculated with CG136 produced 46 to 85 and 51 to 84% of A. flavus DNA from
      kernels and conidia, respectively. Co-inoculation with atoxigenic isolates
      reduced aflatoxin up to 90% and, in some cases, more than predicted by
      competitive exclusion alone. Conidia contained up to 42 ppm aflatoxin B(1),
      indicating airborne conidia as potentially important sources of environmental
      exposure. Aflatoxin-producing potential and sporulation were negatively
      correlated. For some VCGs, sporulation during co-infection was greater than that
      predicted by kernel infection, suggesting that some VCGs increase dispersal while
      sacrificing competitive ability during host tissue colonization. The results
      indicate both life strategy and adaptive differences among A. flavus isolates and
      provide a basis for selection of biocontrol strains with improved competitive
      ability, sporulation, and aflatoxin reduction on target hosts.

PMID- 20055650
TI  - Meta-analysis of the effects of triazole-based fungicides on wheat yield and test
      weight as influenced by Fusarium head blight intensity.
AB  - ABSTRACT Multivariate random-effects meta-analyses were conducted on 12 years of
      data from 14 U.S. states to determine the mean yield and test-weight responses of
      wheat to treatment with propiconazole, prothioconazole, tebuconazole,
      metconazole, and prothioconazole+tebuconazole. All fungicides led to a
      significant increase in mean yield and test weight relative to the check (D; P <
      0.001). Metconazole resulted in the highest overall yield increase, with a D of
      450 kg/ha, followed by prothioconazole+ tebuconazole (444.5 kg/ha),
      prothioconazole (419.1 kg/ha), tebuconazole (272.6 kg/ha), and propiconazole
      (199.6 kg/ha). Metconazole, prothioconazole+tebuconazole, and prothioconazole
      also resulted in the highest increases in test weight, with D values of 17.4 to
      19.4 kg/m(3), respectively. On a relative scale, the best three fungicides
      resulted in an overall 13.8 to 15.0% increase in yield but only a 2.5 to 2.8%
      increase in test weight. Except for prothioconazole+tebuconazole, wheat type
      significantly affected the yield response to treatment; depending on the
      fungicide, D was 110.0 to 163.7 kg/ha higher in spring than in soft-red winter
      wheat. Fusarium head blight (FHB) disease index (field or plot-level severity) in
      the untreated check plots, a measure of the risk of disease development in a
      study, had a significant effect on the yield response to treatment, in that D
      increased with increasing FHB index. The probability was estimated that fungicide
      treatment in a randomly selected study will result in a positive yield increase
      (p(+)) and increases of at least 250 and 500 kg/ha (p(250) and p(500),
      respectively). For the three most effective fungicide treatments (metconazole,
      prothioconazole+tebuconazole, and prothioconazole) at the higher selected FHB
      index, p(+) was very large (e.g., >/=0.99 for both wheat types) but p(500) was
      considerably lower (e.g., 0.78 to 0.92 for spring and 0.54 to 0.68 for soft-red
      winter wheat); at the lower FHB index, p(500) for the same three fungicides was
      0.34 to 0.36 for spring and only 0.09 to 0.23 for soft-red winter wheat.

PMID- 20055651
TI  - Divergence between sympatric rice- and maize-infecting populations of Rhizoctonia
      solani AG-1 IA from Latin America.
AB  - ABSTRACT The basidiomycetous fungus Rhizoctonia solani anastomosis group (AG)-1
      IA is a major pathogen in Latin America causing sheath blight (SB) of rice.
      Particularly in Venezuela, the fungus also causes banded leaf and sheath blight
      (BLSB) on maize, which is considered an emerging disease problem where maize
      replaced traditional rice-cropping areas or is now planted in adjacent fields.
      Our goals in this study were to elucidate (i) the effects of host specialization
      on gene flow between sympatric and allopatric rice and maize-infecting fungal
      populations and (ii) the reproductive mode of the fungus, looking for evidence of
      recombination. In total, 375 isolates of R. solani AG1 IA sampled from three
      sympatric rice and maize fields in Venezuela (Portuguesa State) and two
      allopatric rice fields from Colombia (Meta State) and Panama (Chiriqui State)
      were genotyped using 10 microsatellite loci. Allopatric populations from
      Venezuela, Colombia, and Panama were significantly differentiated (Phi(ST) of
      0.16 to 0.34). Partitioning of the genetic diversity indicated differentiation
      between sympatric populations from different host species, with 17% of the total
      genetic variation distributed between hosts while only 3 to 6% was distributed
      geographically among the sympatric Venezuelan fields. We detected symmetrical
      historical migration between the rice- and the maize-infecting populations from
      Venezuela. Rice- and maize-derived isolates were able to infect both rice and
      maize but were more aggressive on their original hosts, consistent with host
      specialization. Because the maize- and rice-infecting populations are still cross
      pathogenic, we postulate that the genetic differentiation was relatively recent
      and mediated via a host shift. An isolation with migration analysis indicated
      that the maize-infecting population diverged from the rice-infecting population
      between 40 and 240 years ago. Our findings also suggest that maize-infecting
      populations have a mainly recombining reproductive system whereas the rice
      infecting populations have a mixed reproductive system in Latin America.

PMID- 20055652
TI  - Resistance to Fusarium head blight and seedling blight in wheat is associated
      with activation of a cytochrome p450 gene.
AB  - ABSTRACT One plant genotype displays a resistance phenotype at one development
      stage but a susceptible reaction to the same pathogen at another stage, which is
      referred to here as resistance inversion. In wheat, Fusarium head blight (FHB)
      resistant cv. Sumai3 showed a Fusarium seedling blight (FSB)-susceptible reaction
      whereas FHB-susceptible cv. Annong8455 exhibited FSB resistance when challenged
      with a Fusarium asiaticum strain that produces deoxynivalenol (DON). The
      resistance to FHB and FSB in wheat was closely associated with expression of a
      plant cytochrome P450 gene in response to FHB pathogens and mycotoxins.
      Quantitative real-time polymerase chain reaction analyses showed that expression
      of nine defense-related genes in spikes and seedlings was induced by the fungal
      infection, in which a massive accumulation of a plant cytochrome P450 gene,
      CYP709C1, was clearly associated with the resistance reaction in both seedling
      and spike. The FHB-resistant Sumai3 accumulated 7-fold more P450 transcripts than
      did the FHB-susceptible Annong8455, while 84-fold more P450 transcripts were
      accumulated in the FSB-resistant Annong8455 than the FSB-susceptible Sumai3. A
      Fusarium strain with a disrupted Tri5 gene, which is not able to produce the
      first enzyme essential for trichothecene mycotoxin biosynthesis, also induced
      more P450 transcripts in FHB- and FSB-resistant cultivars. The fungal activation
      of the P450 gene was more profound in the FSB-resistant reaction than the FHB
      resistant reaction relative to their susceptible counterparts. DON triggered a
      differential expression of the P450 gene with comparable patterns in spikes and
      seedlings in a resistance-dependent manner. These results may provide a basis for
      dissecting mechanisms underlying FHB and FSB resistance reactions in wheat and
      revealing functions of the cytochrome P450 in plant detoxification and defense.

PMID- 20055653
TI  - Molecular signature of differential virulence in natural isolates of Erwinia
      amylovora.
AB  - ABSTRACT Erwinia amylovora, the causal agent of fire blight, is considered to be
      a genetically homogeneous species based on physiological, biochemical,
      phylogenetic, and genetic analysis. However, E. amylovora strains exhibiting
      differential virulence are isolated from nature. The exopolysaccharide amylovoran
      and type III secretion system (T3SS) are two major yet separate virulence factors
      in E. amylovora. The objective of this study was to investigate whether there is
      a correlation between E. amylovora virulence and levels of virulence gene
      expression. Four wild-type strains (Ea1189, Ea273, Ea110, and CFBP1430), widely
      used in studies of E. amylovora pathogenesis, have been analyzed and compared. E.
      amylovora strains Ea273 and Ea110 elicited higher severity of disease symptoms
      than those of Ea1189 and CFBP1430 on apple cv. Golden Delicious and G16 apple
      root stock plants but not on susceptible Gala plants. In addition, Ea273 and
      Ea110 elicited severe hypersensitive responses within shorter periods of time at
      lower inoculum concentrations than those of Ea1189 and CFBP1430 on tobacco
      plants. Further molecular analyses have revealed that amylovoran production and
      expression of both amylovoran (amsG) and T3SS (dspE and hrpL) genes were
      significantly higher in Ea273 and Ea110 than those in Ea1189 and CFBP1430. Other
      phenotypes such as swarming motility in these four strains also differed
      significantly. These results indicate that E. amylovora strains of different
      origin can be divided into subgroups based on molecular signatures of virulence
      gene expression. Therefore, these molecular signatures may be used to
      differentiate E. amylovora strains, which may have taxonomical and evolutionary
      implications.

PMID- 20055654
TI  - Nematicidal activity of monoterpenoids against the root-knot nematode Meloidogyne
      incognita.
AB  - ABSTRACT Nematicidal activity of 22 monoterpenoids were evaluated in vitro and in
      pot experiments. Twenty of the twenty-two monoterpenoids significantly reduced
      hatching, and 11 reduced J2 mobility of the root-knot nematode Meloidogyne
      incognita at a concentration of 250 mg/liter. In general, compounds with hydroxyl
      and carbonyl groups exhibited higher nematicidal activity than other terpenoids.
      Borneol, carveol, citral, geraniol, and alpha-terpineol showed the highest
      nematicidal activity among the in vitro tested monoterpenoids. These compounds
      exhibited a dose dependent effect, and drastically reduced eggs hatching and J2
      viability at low concentrations. These monoterpenoids, at 100 and 250 mg/kg
      concentration, diminished root galling of tomato plants in pot experiments. The
      results suggest that the selected monoterpenoids, and essential oils with high
      concentration of these compounds, are potential nematicides against Meloidogyne.

PMID- 20055655
TI  - Primary bone lymphoma: a set of unique problems in management.

PMID- 20055656
TI  - Immunotherapy for B-cell lymphoma.

PMID- 20055658
TI  - Total body irradiation plus cyclophosphamide versus busulphan with
      cyclophosphamide as conditioning regimen for patients with leukemia undergoing
      allogeneic stem cell transplantation: a meta-analysis.
AB  - The aim of the study was to compare the therapeutic efficacy of total body
      irradiation (TBI)/cyclophosphamide (CY) versus BU/CY as conditioning regimen for
      leukemia. We electronically searched the Cochrane Central Register of Controlled
      Trials, Medline, Embase, CIBMTR and critically appraised all relevant articles
      (1990.01-2009.04). Comparative studies were evaluated on clinical therapeutic
      effects of TBI/CY and busulphan BU/CY regimens with assessement of engraftment,
      relapse, complications, and disease-free survival (DFS). Eighteen trials totaling
      3172 patients have been assessed. Pooled comparisons of studies indicated that
      for patients with acute leukemia (ALL and AML), the TBI/CY regimen lead to lower
      rates of leukemia relapse, lower transplant-related mortality (TRM), and higher
      DFS, while for chronic myeloid leukemia (CML), the TBI/CY regimen had a higher
      rate of leukemia relapse, lower TRM, and similar DFS. The TBI/CY regimen was
      associated with similar occurrence of engraftment, acute and chronic graft-versus
      host disease (GVHD), but with higher rates of cataract [odds ratio (OR) 12.69, p
      = 0.01], interstitial pneumonitis, later growth or development problems [OR 5.04,
      p = 0.008]. BU/CY regimen was associated with higher rates of complications like
      liver veno-occlusive disease [OR 0.43, p < 0.00001], hemorrhagic cystitis, and
      TRM. Our meta-analysis confirmed that different regimens and type of leukemia may
      affect the complications and outcome. An analysis of the effects of other
      regimens need to be carried out by large sample and well-designed clinical
      trials.

PMID- 20055657
TI  - Thalidomide and lenalidomide as new therapeutics for the treatment of chronic
      lymphocytic leukemia.
AB  - The use of nucleoside analog-based chemo-immunotherapeutic regimens over the last
      decade has significantly improved outcomes in patients with chronic lymphocytic
      leukemia (CLL). Nonetheless, virtually all patients with CLL relapse from
      chemoimmmunotherapy and current available therapies are not curative. Identifying
      therapies that effectively eliminate CLL cells and lack immunesuppression
      represent an exciting new therapeutic approach. IMiDs are a class of
      immunomodulating drugs that increase T-cell and NK-cell directed killing of tumor
      cells. The first generation molecule is thalidomide followed by a second
      generation molecule lenalidomide that lacks neurotoxicity and is being explored
      more extensively in clinical trials. Lenalidomide has been shown to benefit
      patients with multiple myeloma, myelodysplastic syndromes, and lymphoma. Initial
      reports in patients with relapsed and refractory CLL have shown promising
      responses. In a subset of patients with CLL complete responses have been noted.
      Subsequent studies, however, have suggested that this class of drug can also have
      serious and potentially life-threatening side effects including myelosuppression,
      tumor flare reaction and in a small subset of patients tumor lysis syndrome.
      Tumor flare with both thalidomide and lenalidomide appear to be disease specific
      to CLL and may reflect clinical manifestation of CLL tumor cell activation. As a
      consequence of these disease specific effects, the optimal safe dose of
      lenalidomide in CLL remains to be determined but appears to be lower than that
      tolerated in other B-cell malignancies. To date, biomarkers for response remain
      poorly defined and the relationship of clinical benefit to tumor flare is
      uncertain. This review examines the existing literature on the use of IMiDs in
      patients with CLL and provides suggestions for future research in this area.

PMID- 20055659
TI  - Kinase domain mutations and responses to dose escalation in chronic myeloid
      leukemia resistant to standard dose imatinib mesylate.
AB  - We studied kinase domain (KD) mutations, response to dose escalation, event free
      survival (EFS), and overall survival (OS) of 90 patients with chronic phase CML
      who were resistant to imatinib mesylate (IM) 400 mg. IM was escalated to 800 mg
      daily. There were 65 patients with hematologic failure and 25 with cytogenetic
      failure. Median duration on IM at resistance detection was 18 months (range, 3
      48). Twenty nine (32.2%) patients had KD mutations. Of the 29, the most common
      were T315I in nine (31.2%) and G250E in eight (27.6%). No clinical or laboratory
      factor predicted for mutation detection. Of 90 patients, 50 (55.5%) achieved a
      complete hematologic response and 35 (39%) a major cytogenetic response. At a
      median of 18 months (range 3-40), 35 patients (39%) are event free and 84 (93%)
      are alive. The 2 year EFS and OS were 34% and 93%, respectively. The projected 2
      year EFS was superior for patients with cytogenetic failure compared to those
      with hematologic failures (73 vs. 22%, p = 0.0001). Dose decreases were necessary
      in 16 (18%) and interruptions in 31 (34%). KD mutations were detected in a third
      of patients with T315I being the most common. IM dose escalation can induce
      sustained responses in patients with cytogenetic failures.

PMID- 20055660
TI  - Efficacy of lenalidomide in patients with chronic lymphocytic leukemia with high
      risk cytogenetics.
AB  - Patients with chronic lymphocytic lymphoma (CLL) with high-risk cytogenetics
      [del(11q)(q22.3) or del(17p)(p13.1)] have limited therapeutic options and their
      prognosis remains poor. This analysis was conducted to determine the clinical
      activity of lenalidomide in patients with high-risk disease. Relapsed/refractory
      patients with CLL enrolled in a phase II clinical trial who had del(11q)(q22.3)
      or del(17p)(p13.1) were included in this analysis. Patients received single agent
      lenalidomide for 21 days of the 4 week treatment cycle. The overall response rate
      among patients with high-risk cytogenetics was 38%, with 19% of patients
      achieving a complete response. Median progression-free survival was 12.1 months,
      which is higher than demonstrated with other agents in comparable patient
      populations. In addition, the estimated 2-year survival probability was 58%,
      demonstrating that the responses achieved with lenalidomide are durable, even in
      patients with CLL with high-risk disease with poor risk cytogenetics.

PMID- 20055661
TI  - Dental stem cell therapy with calcium hydroxide in dental pulp capping.
AB  - Calcium hydroxide has been extensively and steadily used for direct pulp capping
      in modern clinical dentistry. As it was known to have potential to induce hard
      tissue repair, this chemical has been applied to the exposed dental pulp and the
      hard tissue is expected to be regenerated above the pulp. During the reparative
      process of exposed pulp, primary odontoblasts that were lost as a result of
      extensive damage are replaced with newly differentiated odontoblast-like cells.
      This process is known to follow the sequential steps of proliferation, migration,
      and differentiation of progenitor cells. This research will examine the
      relationship between calcium hydroxide and the recruitment, proliferation, and
      mineralization of postnatal dental stem cells, obtained from an immature dental
      tissue of beagle dogs. Immunocytochemical staining and reverse transcriptase
      polymerase chain reaction were used to identify the putative stem cell markers.
      Immunoblot analysis, wound healing assay, cell migration assay, and alizarin red
      staining were used to evaluate proliferation, migration, and mineralization
      capacity of the calcium hydroxide-treated stem cells. As an in vivo study, a
      combination of calcium hydroxide and autologous dental pulp stem cells (DPSCs)
      was applied for the treatment of intentionally created tooth defects on the
      premolars and the molars in beagle dogs to observe dentin regeneration. Ex vivo
      expanded DPSCs and periodontal ligament stem cells expressed STRO-1 and CD146,
      the mesenchymal stem cell markers. It was evident that calcium hydroxide
      increased recruitment, migration, proliferation, and mineralization of the DPSCs
      and periodontal ligament stem cells. Such results are valuable for future
      availability of DPSCs, which are recently focused as the stem cell reservoir for
      regeneration of dentin upon tooth injury, as well as for elucidation of the role
      of calcium hydroxide in pulp capping therapy.

PMID- 20055662
TI  - Porcine endothelial cells cocultured with smooth muscle cells became procoagulant
      in vitro.
AB  - Endothelial cell (EC) seeding represents a promising approach to provide a
      nonthrombogenic surface on vascular grafts. In this study, we used a porcine
      EC/smooth muscle cell (SMC) coculture model that was previously developed to
      examine the efficacy of EC seeding. Expression of tissue factor (TF), a primary
      initiator in the coagulation cascade, and TF activity were used as indicators of
      thrombogenicity. Using immunostaining, primary cultures of porcine EC showed a
      low level of TF expression, but a highly heterogeneous distribution pattern with
      14% of ECs expressing TF. Quiescent primary cultures of porcine SMCs displayed a
      high level of TF expression and a uniform pattern of staining. When we used a two
      stage amidolytic assay, TF activity of ECs cultured alone was very low, whereas
      that of SMCs was high. ECs cocultured with SMCs initially showed low TF activity,
      but TF activity of cocultures increased significantly 7-8 days after EC seeding.
      The increased TF activity was not due to the activation of nuclear factor kappa-B
      on ECs and SMCs, as immunostaining for p65 indicated that nuclear factor kappa-B
      was localized in the cytoplasm in an inactive form in both ECs and SMCs. Rather,
      increased TF activity appeared to be due to the elevated reactive oxygen species
      levels and contraction of the coculture, thereby compromising the integrity of EC
      monolayer and exposing TF on SMCs. The incubation of cocultures with N-acetyl
      cysteine (2 mM), an antioxidant, inhibited contraction, suggesting involvement of
      reactive oxygen species in regulating the contraction. The results obtained from
      this study provide useful information for understanding thrombosis in tissue
      engineered vascular grafts.

PMID- 20055663
TI  - 3D PLGA scaffolds improve differentiation and function of bone marrow mesenchymal
      stem cell-derived hepatocytes.
AB  - Liver tissue engineering with hepatic stem cells provides a promising alternative
      to liver transplantation in patients with acute and chronic hepatic failure. In
      this study, a three-dimensional (3D) bioscaffold was introduced for
      differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into
      hepatocytes. For hepatocyte differentiation, third passage BMSCs isolated from
      normal adult F344 rats were seeded into collagen-coated poly(lactic-co-glycolic
      acid) (C-PLGA) 3D scaffolds with hepatocyte differentiation medium for 3 weeks.
      Hepatogenesis in scaffolds was characterized by reverse transcript PCR, western
      blot, confocal laser scanning microscopy (CLSM), periodic acid-Schiff staining,
      histochemistry, and biochemical assays with hepatic-specific genes and markers. A
      monolayer culture system was used as a control differentiation group. The results
      showed that isolated cells possessed the basic features of BMSCs. Differentiated
      hepatocyte-like cells in C-PLGA scaffolds expressed hepatocyte-specific markers
      [eg, albumin (ALB), alpha-fetoprotein, cytokeratin 18, hepatocyte nuclear factor
      4alpha, and cytochrome P450] at mRNA and protein levels. Most markers were
      expressed in C-PLGA group 1 week earlier than in the control group. Results of
      biocompatibility indicated that the differentiated hepatocyte-like cells grew
      more stably in C-PLGA scaffolds than that in controls during a 3-week
      differentiation period. The significantly higher metabolic functions in
      hepatocyte-like cells in the C-PLGA scaffold group further demonstrated the
      important role of the scaffold. CONCLUSION: As the phenomenon of
      transdifferentiation is uncommon, our successful transdifferentiation rates of
      BMSCs to mature hepatocytes prove the superiority of the C-PLGA scaffold in
      providing a suitable environment for such a differentiation. This material can
      possibly be used as a bioscaffold for liver tissue engineering in future clinical
      therapeutic applications.

PMID- 20055664
TI  - Optimizing empirical antimicrobial therapy for infection due to gram-negative
      pathogens in the intensive care unit: utility of a combination antibiogram.
AB  - OBJECTIVE: To determine whether the use of dual antimicrobial therapy based on
      the results of a combination antibiotic susceptibility report (antibiogram)
      increases the likelihood of selecting adequate empirical coverage in critically
      ill patients with infection due to potentially resistant gram-negative pathogens.
      DESIGN: Retrospective data analysis. SETTING: Urban academic medical center.
      METHODS: An analysis of culture results and susceptibility data from intensive
      care unit patients determined by the clinical microbiology laboratory was
      performed. The proportion of 5 common gram-negative pathogens susceptible to
      monotherapy with 1 of 3 antipseudomonal antibiotics (piperacillin-tazobactam,
      ceftazidime, or imipenem) was compared with the proportion susceptible to each of
      these 3 "backbone" agents plus 1 of 4 additional antimicrobial agents used in
      combination. RESULTS: More than 5,000 clinical isolates were examined. When all
      isolates recovered during the entire study period were included, the addition of
      any of the second antibiotics studied to each of the 3 backbone agents
      significantly increased the likelihood of covering the causative pathogen (P <
      .01 for each). The benefit of combination therapy was variable when results for
      each of the 5 organisms were examined individually. When temporal trends in
      susceptibility were examined, the decrease in the proportion of organisms
      susceptible to monotherapy was statistically significant for both imipenem and
      ceftazidime (P < .01). CONCLUSIONS: Reporting antibiotic susceptibility data in
      the form of a combination antibiogram may be useful to clinicians who are
      considering empirical antimicrobial therapy in the intensive care unit.

PMID- 20055665
TI  - Percutaneous renal access: the learning curve of a simplified approach.
AB  - BACKGROUND AND PURPOSE: Fluoroscopically guided techniques to access the kidney
      percutaneously with low exposure to radiation have been used successfully for
      many years in our training center. The purpose of this study was to analyze the
      learning process and to establish the number of procedures necessary for a
      nonexperienced urologist to achieve competence at performing percutaneous renal
      access. MATERIALS AND METHODS: Eighty-two percutaneous renal accesses in patients
      with renal stones or ureteropelvic junction obstruction were evaluated. The time
      needed to perform a correct puncture and the fluoroscopic screening time were
      recorded for each renal access. Descriptive analysis, analysis of variance, and a
      Markov chain were used to analyze the results. RESULTS: The rate of success
      increased from 82.5% to 97.6% after the first 40 punctures. Puncture time and
      fluoroscopy time decreased as the number of procedures increased. Incidence of
      complications was 30% for the first 20 cases, decreasing to 10% in the next 20
      cases and 3.7% in the last 33 cases. CONCLUSIONS: The fluoroscopy-guided approach
      used in this study is an effective and reproducible technique. Our analysis
      revealed that at least 50 procedures are needed to acquire reliable competence in
      obtaining access to the kidney.

PMID- 20055666
TI  - Influenza vaccination among healthcare workers: ten-year experience of a large
      healthcare organization.
AB  - OBJECTIVE: To describe the results of different measures implemented to improve
      adherence to the healthcare worker (HCW) influenza immunization program at BJC
      HealthCare during the period from 1997 through 2007. DESIGN: Descriptive
      retrospective study. SETTING: BJC HealthCare, a 13-hospital nonprofit healthcare
      organization in the Midwest. METHODS: We reviewed and analyzed HCW influenza
      vaccination data from all BJC HealthCare Occupational Health Services and
      hospitals during the period from 1997 through 2007. Occupational health staff,
      infection prevention personnel, and key influenza vaccination campaign leaders
      were also interviewed regarding implementation measures during the study years.
      RESULTS: At the end of 2007, BJC HealthCare had approximately 26,000 employees.
      With the use of multiple progressive interventions, influenza vaccination rates
      among BJC employees increased from 45% in 1997 to 72% in 2007 (P < .001). The
      influenza vaccination rate in 2007 was significantly higher than in 2006: 72%,
      compared with 54% (P < .001). Five hospitals had influenza vaccination rates that
      exceeded the target goal of 80% in 2007. The most successful interventions were
      adding influenza vaccination rates to the quality scorecard incentive program and
      the use of declination statements, both of which were implemented in 2007. The
      most important barriers to success identified by interview respondents were HCWs'
      misconceptions about influenza vaccination and a perceived lack of leadership
      support. CONCLUSIONS: Influenza vaccination rates among HCWs significantly
      improved with multiple interventions over the years. However, the BJC HealthCare
      influenza vaccination target of 80% was not attained at all hospitals with these
      measures. More aggressive interventions, such as implementing mandatory influenza
      vaccination policies, are needed to achieve higher vaccination rates.

PMID- 20055667
TI  - Chemistry of Hofmeister anions and osmolytes.
AB  - The study of the interactions of salts and osmolytes with macromolecules in
      aqueous solution originated with experiments concerning protein precipitation
      more than 100 years ago. Today, these solutes are known to display recurring
      behavior for myriad biological and chemical processes. Such behavior depends both
      on the nature and concentration of the species in solution. Despite the
      generality of these effects, our understanding of the molecular-level details of
      ion and osmolyte specificity is still quite limited. Here, we review recent
      studies of the interactions between anions and urea with model macromolecular
      systems. A mechanism for specific ion effects is elucidated for aqueous systems
      containing charged and uncharged polymers, polypeptides, and proteins. The
      results clearly show that the effects of the anions are local and involve direct
      interactions with macromolecules and their first hydration shell. Also, a
      hydrogen-bonding mechanism is tested for the urea denaturation of proteins with
      some of these same systems. In that case, direct hydrogen bonding can be largely
      discounted as the key mechanism for urea stabilization of uncollapsed and/or
      unfolded structures.

PMID- 20055668
TI  - Electrostatics of strongly charged biological polymers: ion-mediated interactions
      and self-organization in nucleic acids and proteins.
AB  - Charges on biological polymers in physiologically relevant solution conditions
      are strongly screened by water and salt solutions containing counter-ions.
      However, the entropy of these counterions can result in surprisingly strong
      interactions between charged objects in water despite short screening lengths,
      via coupling between osmotic and electrostatic interactions. Widespread work in
      theory, experiment, and computation has been carried out to gain a fundamental
      understanding of the rich, yet sometimes counterintuitive, behavior of these
      polyelectrolyte systems. Examples of polyelectrolyte association in biology
      include DNA packaging and RNA folding, as well as aggregation and self
      organization phenomena in different disease states.

PMID- 20055669
TI  - Novel computational methods for nanostructure electronic structure calculations.
AB  - Experimentally relevant nanocrystals often contain a few thousands to hundreds of
      thousands of atoms. Yet, to understand their electronic structures, surface and
      impurity effects, atomic relaxations, interior electric fields, carrier dynamics,
      and transports, it is often necessary to carry out atomistic simulations. Owing
      to the advance of recent algorithm developments and improved supercomputer
      powers, it is now possible to calculate such nanocrystals based on ab initio
      methods. In this review, we discuss the numerical algorithms (the plane-wave
      pseudopotential method and the real-space finite-difference method) used in
      conventional density-functional-theory calculations, which enable the simulations
      of systems up to one or two thousand atoms. We also introduce methods designed
      specifically for nanostructure calculations. These methods [the charge-patching
      method (CPM) and the linear scaling three-dimensional fragment method (LS3DF)]
      can be used to calculate systems with hundreds of thousands of atoms. Whereas CPM
      is an approximation with ab initio quality, the LS3DF method is an O(N) method
      with essentially the same results as the direct methods. The computational
      aspects of the algorithms, especially for their parallelization scalability, are
      also emphasized in the review.

PMID- 20055670
TI  - The diabatic picture of electron transfer, reaction barriers, and molecular
      dynamics.
AB  - Diabatic states have a long history in chemistry, beginning with early valence
      bond pictures of molecular bonding and extending through the construction of
      model potential energy surfaces to the modern proliferation of methods for
      computing these elusive states. In this review, we summarize the basic principles
      that define the diabatic basis and demonstrate how they can be applied in the
      specific context of constrained density functional theory. Using illustrative
      examples from electron transfer and chemical reactions, we show how the diabatic
      picture can be used to extract qualitative insight and quantitative predictions
      about energy landscapes. The review closes with a brief summary of the challenges
      and prospects for the further application of diabatic states in chemistry.

PMID- 20055671
TI  - Functional motifs in biochemical reaction networks.
AB  - The signal-response characteristics of a living cell are determined by complex
      networks of interacting genes, proteins, and metabolites. Understanding how cells
      respond to specific challenges, how these responses are contravened in diseased
      cells, and how to intervene pharmacologically in the decision-making processes of
      cells requires an accurate theory of the information-processing capabilities of
      macromolecular regulatory networks. Adopting an engineer's approach to control
      systems, we ask whether realistic cellular control networks can be decomposed
      into simple regulatory motifs that carry out specific functions in a cell. We
      show that such functional motifs exist and review the experimental evidence that
      they control cellular responses as expected.

PMID- 20055673
TI  - Hyper-Raman scattering by molecular vibrations.
AB  - This article reviews the experimental and theoretical aspects of vibrational
      hyper-Raman scattering from molecules. Particular emphasis is placed on hyper
      Raman scattering enhanced by nanostructured metal surfaces and by two-photon
      electronic resonance.

PMID- 20055672
TI  - Subcellular dynamics and protein conformation fluctuations measured by Fourier
      imaging correlation spectroscopy.
AB  - Novel high signal-to-noise spectroscopic experiments that probe the dynamics of
      microscopic objects have the potential to reveal complex intracellular
      biochemical mechanisms, or the slow relaxations of soft matter systems. This
      article reviews the implementation of Fourier imaging correlation spectroscopy
      (FICS), a phase-selective approach to fluorescence fluctuation spectroscopy that
      employs a unique route to elevate signal levels while acquiring detailed
      information about molecular coordinate trajectories. The review demonstrates the
      broad applicability of FICS by discussing two recent studies. The dynamics of
      Saccharomyces cerevisiae yeast mitochondria are characterized with FICS and
      provide detailed information about the influence of specific cytoskeletal
      elements on the movement of this organelle. In another set of experiments,
      polarization-modulated FICS captures conformational dynamics and molecular
      translational dynamics of the fluorescent protein DsRed, and analyses by four
      point correlation and joint distribution functions of the corresponding data
      reveal statistically meaningful pathways of DsRed switching between different
      optical conformations.

PMID- 20055674
TI  - On walking in the footprints of giants.
AB  - This article tells of a lifelong fascination with light, a messenger bearing
      information from realms ranging from the galactic to the submicroscopic. Personal
      interactions have shaped and informed this life journey. Accounts of some of the
      most important of these are related. Infrared and electronic spectra have been
      obtained, often for the first time, for many small free radicals and molecular
      ions-short-lived reaction intermediates in most chemical processes. The infrared
      spectrum of a molecule tells how its atoms vibrate with respect to one another
      and is as characteristic of the molecule as a fingerprint is of a person.
      Analysis of this spectrum provides sometimes surprising information about the
      structure and chemical bonding of the molecule in its lowest-energy electronic
      state. The electronic spectrum provides information on the molecule in more
      highly excited electronic states, in which its structure or reaction pattern may
      change or it may decompose.

PMID- 20055675
TI  - Oxide surface science.
AB  - Most metals are oxidized under ambient conditions, and metal oxides show
      interesting and technologically promising properties. This has motivated much
      recent research on oxide surfaces. The combination of scanning tunneling
      microscopy with first-principles density functional theory-based computational
      techniques provides an atomic-scale view of the properties of metal-oxide
      materials. Surface polarity is a key concept for predicting the stability of
      oxide surfaces and is discussed using ZnO as an example. This review also
      highlights the role of surface defects for surface reactivity, and their
      interplay with defects in the bulk, for the case of TiO(2). Ultrathin metal-oxide
      films, grown either through reactive evaporation on metal single crystals or
      through oxidation of metal alloys (such as Al(2)O(3)/NiAl), have gained
      popularity as supports for planar model catalysts. The surface oxides that form
      upon oxidation on Pt-group metals (e.g., Ru, Rh, Pd, and Pt) are considered as
      model systems for CO oxidation.

PMID- 20055676
TI  - Dynamics on the way to forming glass: bubbles in space-time.
AB  - We review a theoretical perspective of the dynamics of glass-forming liquids and
      the glass transition, a perspective developed during this past decade based on
      the structure of trajectory space. This structure emerges from spatial
      correlations of dynamics that appear in disordered systems as they approach
      nonergodic or jammed states. It is characterized in terms of dynamical
      heterogeneity, facilitation, and excitation lines. These features are associated
      with a newly discovered class of nonequilibrium phase transitions. Equilibrium
      properties have little, if anything, to do with it. The broken symmetries of
      these transitions are obscure or absent in spatial structures, but they are vivid
      in space-time (i.e., trajectory space). In our view, the glass transition is an
      example of this class of transitions. The basic ideas and principles we review
      were originally developed through the analysis of idealized and abstract models.
      Nevertheless, the central ideas are easily illustrated with reference to
      molecular dynamics of more realistic atomistic models, and we use that
      illustrative approach here.

PMID- 20055677
TI  - Molecular structural dynamics probed by ultrafast X-ray absorption spectroscopy.
AB  - The ability to visualize molecular structure in the course of a chemical reaction
      or a biological function has been a dream of scientists for decades. X-ray
      absorption spectroscopy (XAS) is ideal in this respect because it is chemically
      selective and can be implemented in any type of medium. Furthermore, using X-ray
      absorption near-edge structure (XANES) and extended X-ray absorption fine
      structure (EXAFS) in laser pump/X-ray probe experiments allows the retrieval of
      not only the local geometric structure of the system under study, but also the
      underlying electronic structure changes that drive the structural dynamics. We
      review recent developments in picosecond and femtosecond XAS applied to molecular
      systems in solution. Examples on ultrafast photoinduced processes such as
      intramolecular electron transfer, low-to-high spin change, and bond formation are
      presented.

PMID- 20055678
TI  - Tuned range-separated hybrids in density functional theory.
AB  - We review density functional theory (DFT) within the Kohn-Sham (KS) and the
      generalized KS (GKS) frameworks from a theoretical perspective for both time
      independent and time-dependent problems. We focus on the use of range-separated
      hybrids within a GKS approach as a practical remedy for dealing with the
      deleterious long-range self-repulsion plaguing many approximate implementations
      of DFT. This technique enables DFT to be widely relevant in new realms such as
      charge transfer, radical cation dimers, and Rydberg excitations. Emphasis is put
      on a new concept of system-specific range-parameter tuning, which introduces
      predictive power in applications considered until recently too difficult for DFT.

PMID- 20055679
TI  - Biological cluster mass spectrometry.
AB  - This article reviews the new physics and new applications of secondary ion mass
      spectrometry using cluster ion probes. These probes, particularly C(60), exhibit
      enhanced molecular desorption with improved sensitivity owing to the unique
      nature of the energy-deposition process. In addition, these projectiles are
      capable of eroding molecular solids while retaining the molecular specificity of
      mass spectrometry. When the beams are microfocused to a spot on the sample,
      bioimaging experiments in two and three dimensions are feasible. We describe
      emerging theoretical models that allow the energy-deposition process to be
      understood on an atomic and molecular basis. Moreover, experiments on model
      systems are described that allow protocols for imaging on biological materials to
      be implemented. Finally, we present recent applications of imaging to biological
      tissue and single cells to illustrate the future directions of this methodology.

PMID- 20055680
TI  - Superresolution imaging using single-molecule localization.
AB  - Superresolution imaging is a rapidly emerging new field of microscopy that
      dramatically improves the spatial resolution of light microscopy by over an order
      of magnitude (approximately 10-20-nm resolution), allowing biological processes
      to be described at the molecular scale. Here, we discuss a form of
      superresolution microscopy based on the controlled activation and sampling of
      sparse subsets of photoconvertible fluorescent molecules. In this single-molecule
      based imaging approach, a wide variety of probes have proved valuable, ranging
      from genetically encodable photoactivatable fluorescent proteins to
      photoswitchable cyanine dyes. These have been used in diverse applications of
      superresolution imaging: from three-dimensional, multicolor molecule localization
      to tracking of nanometric structures and molecules in living cells. Single
      molecule-based superresolution imaging thus offers exciting possibilities for
      obtaining molecular-scale information on biological events occurring at variable
      timescales.

PMID- 20055681
TI  - Complex fluids: probing mechanical properties of biological systems with optical
      tweezers.
AB  - The mechanical properties of cells are crucial for cell sensing and reaction to
      mechanical environments. This review describes the basic principles of optical
      tweezers and their use as force sensors for studying the mechanical properties of
      biological systems. It covers experiments of four groups of biological systems
      arranged by increasing complexity: (a) packaging DNA into viral capsids by
      bacteriophage portal motors and the dynamical stiffness of DNA upon protein
      binding, (b) actin-coated giant vesicles and the myosin-II embedded actin polymer
      network, (c) suspension cells, and (d) adhesion cells. These examples demonstrate
      how optical tweezers have been used to improve the understanding of the
      mechanical properties of biological systems at subcellular and molecular levels.

PMID- 20055682
TI  - Bio-enabled synthesis of metamaterials.
AB  - Biological systems offer more than an inspiration for the spontaneous
      hierarchical organization of matter at length scales between 1 and 1000 nm. They
      also provide useful principles and molecular building blocks that have recently
      emerged with the proven ability to generate extended three-dimensional structures
      of hybrid biotic/abiotic components arranged with molecular precision. These
      principles and tools draw from the methods of molecular biology and modern
      biochemistry and are expected to provide unmatched flexibility in building
      supramolecular architectures, notably structures made of artificial atoms whose
      coupled responses to electromagnetic or elastic excitations have been predicted
      to yield astonishing properties unparalleled by any conventional materials. To
      illustrate the potential of merging bio-enabled organization with metamaterials
      synthesis, we provide here a succinct overview of the architectural constraints
      leading to metamaterial behavior together with examples of biological material
      assembly that are particularly promising to comply with these constraints.

PMID- 20055683
TI  - From artificial atoms to nanocrystal molecules: preparation and properties of
      more complex nanostructures.
AB  - Quantum dots, which have found widespread use in fields such as biomedicine,
      photovoltaics, and electronics, are often called artificial atoms due to their
      size-dependent physical properties. Here this analogy is extended to consider
      artificial nanocrystal molecules, formed from well-defined groupings of
      plasmonically or electronically coupled single nanocrystals. Just as a hydrogen
      molecule has properties distinct from two uncoupled hydrogen atoms, a key feature
      of nanocrystal molecules is that they exhibit properties altered from those of
      the component nanoparticles due to coupling. The nature of the coupling between
      nanocrystal atoms and its response to vibrations and deformations of the
      nanocrystal molecule bonds are of particular interest. We discuss synthetic
      approaches, predicted and observed physical properties, and prospects and
      challenges toward this new class of materials.

PMID- 20055684
TI  - Thymoma in children: report of 2 cases and review of the literature.
AB  - Thymoma is an uncommon and slow-growing neoplasm. It is derived from thymic
      epithelial cells and comprises about 20% to 30% of mediastinal masses in adults,
      but only about 1% in pediatric patients. Patients usually present with mass
      associated respiratory symptoms, superior vena cava syndrome, or paraneoplastic
      syndrome including myasthenia gravis, pure red cell aplasia, or acquired
      hypogammaglobulinemia, and connective tissue disorders. Due to the limited number
      of cases, knowledge, and experience with thymoma in pediatric patients, the
      diagnosis and treatment are very challenging for this age group. In this article,
      we report 2 cases of thymoma in childhood and provide a comprehensive review and
      analysis of the reported pediatric cases in the past 30 years (total of 32
      cases). We found that patients younger than age 10 years were predominantly male
      (M:F = 6:1) and had advanced tumor stage more frequent than patients older than
      age 10 (P = .03). There were also significant associations of male sex with more
      advanced tumor stage and less favorable outcome (P = .03). These findings suggest
      that age and sex may be additional potential prognostic contributors in pediatric
      patients with thymoma. The clinicopathologic features, differential diagnosis,
      and current therapeutic recommendations of this uncommon tumor in pediatric
      patients are also addressed.

PMID- 20055685
TI  - Pediatric epithelial salivary gland tumors: spectrum of histologies and
      cytogenetics at a children's hospital.
AB  - There are conflicting reports regarding the relative frequency of benign and
      malignant epithelial salivary gland tumors in children. There are only a few
      reports of the cytogenetic abnormalities in the pleomorphic adenomas (PA) that
      arise in children, and even less information regarding the pleomorphic adenoma
      gene 1 (PLAG1) and high motility group A2 (HMGA2 ) histochemical staining in PAs,
      or their correlation with histologic types (stromal vs epithelial predominance).
      A retrospective 14 year review of epithelial salivary gland tumors encountered at
      a children's hospital identified 13 tumors: 12 PAs and 1 acinic cell carcinoma
      (ACC). No mucoepidermoid carcinomas were identified. Tumors arose in the parotid
      (7) and other sites (2 submandibular, 4 minor). Ten PAs in our cohort had
      cytogenetic studies. Four were normal, 5 involved 8q12, and 1 involved 12q13.
      Immunohistochemistry identified an additional 2 PAs with PLAG1 staining, and 5
      additional PAs with HMGA2 staining. One tumor with ins(18;8)(q21.1;q12q22.2) had
      no PLAG1 staining, but stained with HMGA2. This ins(18;8) may not have involved
      the PLAG1 gene. There was no demonstrable correlation of 8q12/PLAG1 staining or
      12q13/HMGA2 staining with histologic type. Thus we found abnormalities in either
      8q12/PLAG1 staining or 12q13/HMGA2 staining in all PAs. The HMGA2 staining in 50%
      of PAs suggests that it may be more frequently involved in PAs than previously
      thought based on cytogenetic studies, at least in children.

PMID- 20055686
TI  - Circadian timing in cancer treatments.
AB  - The circadian timing system is composed of molecular clocks, which drive 24-h
      changes in xenobiotic metabolism and detoxification, cell cycle events, DNA
      repair, apoptosis, and angiogenesis. The cellular circadian clocks are
      coordinated by endogenous physiological rhythms, so that they tick in synchrony
      in the host tissues that can be damaged by anticancer agents. As a result,
      circadian timing can modify 2- to 10-fold the tolerability of anticancer
      medications in experimental models and in cancer patients. Improved efficacy is
      also seen when drugs are given near their respective times of best tolerability,
      due to (a) inherently poor circadian entrainment of tumors and (b) persistent
      circadian entrainment of healthy tissues. Conversely, host clocks are disrupted
      whenever anticancer drugs are administered at their most toxic time. On the other
      hand, circadian disruption accelerates experimental and clinical cancer
      processes. Gender, circadian physiology, clock genes, and cell cycle critically
      affect outcome on cancer chronotherapeutics. Mathematical and systems biology
      approaches currently develop and integrate theoretical, experimental, and
      technological tools in order to further optimize and personalize the circadian
      administration of cancer treatments.

PMID- 20055687
TI  - Cultivating regenerative medicine innovation in China.
AB  - AIM: While China has become a significant contributor and prolific publisher in
      regenerative medicine, its role in the field is not well understood. We analyze
      how capacity in regenerative medicine was built in China to identify some of its
      main strengths and challenges. MATERIALS & METHODS: This case study of
      regenerative medicine in China is primarily based on interviews with experts in
      China, including researchers, policy makers, clinicians, representatives of firms
      and regulators. RESULTS: Our analysis shows that diverse groups are active in
      this field in China. Leading research groups are contributing extensively to
      international peer-reviewed journals. Strong governmental support and recruitment
      of highly trained Chinese scientists from abroad has made it possible for China
      to rapidly build up capacity in regenerative medicine. However, some hospitals in
      China are offering stem cell therapies with limited scientific evidence
      supporting their efficacy/safety, and international skepticism of medical
      research in China presents a challenge to the development of the field.
      CONCLUSION: China has been able to catapult itself into the forefront of
      regenerative medicine but needs to address current regulatory challenges in order
      to secure its position in this emerging field.

PMID- 20055688
TI  - Emerging drugs in sepsis.
AB  - IMPORTANCE OF THE FIELD: Sepsis remains a major cause of death in intensive care
      units. Despite an intense research, a new drug that is effective in reducing
      mortality in sepsis is still awaited. AREAS COVERED IN THIS REVIEW: The
      literature was analyzed with Pubmed() during the 2008 - 2009 period. If required,
      seminal articles published before 2008 were cited. Clinical trials focusing on
      'sepsis' were first assessed. Next, relevant experimental data in this field were
      reported. WHAT THE READER WILL GAIN: The goal of the review is to determine the
      role for new licensed antibiotics, to give an insight into the conflict on
      adjuvant therapies and to disclose new experimental concepts. TAKE HOME MESSAGE:
      New licensed antibiotics will offer the opportunity to refine the treatment
      choices. Direct hemoperfusion using polymyxin B-immobilized fiber column may be
      an option in sepsis due to Gram-negative bacilli. Among non-antibiotic drugs, new
      ongoing studies will clarify the role of drotrecogin alfa (activated) and low
      dose hydrocortisone. The modulation of monocytic human leukocyte antigen-DR seems
      the most prominent treatment. The use of cardiovascular drugs requires well
      conducted clinical trials. The regulation of high mobility group box 1, adenosine
      blockade or correction of the impaired energy production is still at the
      experimental level.

PMID- 20055689
TI  - Emerging drugs for acute myocardial infarction.
AB  - IMPORTANCE OF THE FIELD: The present review is aimed at going over the
      pharmacological profile (and the clinical impact) of the emerging drugs involved
      in the management of patients with ST-elevation myocardial infarction (STEMI) in
      order to provide the cardiologists who deal with these patients in the early
      phase with the most recent evidence on this topic. AREAS COVERED IN THIS REVIEW:
      Anticoagulant and antiplatelet drugs are the main cornerstones of therapy in the
      treatment of STEMI patients undergoing primary percutaneous coronary intervention
      (PCI). The main issues that clinicians have to deal with are represented by
      balancing thrombotic and bleeding risks. In tailoring therapy, variables such as
      age, sex and previous disease should be taken into account, as well as ongoing
      complications (such as acute renal failure) that could affect hemostasis. Despite
      the well-established clinical benefits of antiplatelet agents, questions remain,
      mainly surrounding potential for variable platelet response, which are strictly
      related to non-genetic (i.e., diet, drug-drug interaction, clinical factors such
      as obesity, diabetes mellitus, and inflammation) and genetic determinants. WHAT
      THE READER WILL GAIN: In their daily practice, cardiologists cannot abstract from
      the knowledge and updating on the ongoing research fields as well as the newly
      developed drugs, which they should frame in the very patient in the attempt to
      the develop a personalized medical strategy. These include also the
      pharmacological option(s) in the treatment of the reperfusion injury, the
      metabolic aspects and the stem cell therapy. TAKE HOME MASSAGE: In our opinion,
      the goal of ongoing research on the pharmacological approach to STEMI patients is
      a personalized medical strategy that relies on critical clinicians who merge
      newly developed acquisitions on this topic and a more complete, systemic and
      critical approach to the patient.

PMID- 20055690
TI  - Emerging therapy for the treatment of acute lymphoblastic leukemia.
AB  - IMPORTANCE OF THE FIELD: Over the last few decades, advances in acute
      lymphoblastic leukemia (ALL) therapy have led to long-term survival rates of >
      80% in children; however, comparable rates have yet to be achieved in adults, and
      a large majority of patients relapse from their disease. AREAS COVERED IN THIS
      REVIEW: The review describes historical therapy and advancements in ALL treatment
      over the past few decades, while providing a concise review of the future
      direction of ALL therapy. Literature was collected through peer reviewed journals
      and the Pharmaprojects drug profile for ALL. WHAT THE READER WILL GAIN: Current
      information regarding prognostic factors for relapse, salvage therapy options and
      emerging drugs are provided in the review. TAKE HOME MESSAGE: Development of new
      drugs with novel mechanisms, unique formulations of existing medications, as well
      as manipulation of current combinations of drugs remain vital to the success in
      adult ALL.

PMID- 20055691
TI  - The role of glimepiride in the treatment of type 2 diabetes mellitus.
AB  - IMPORTANCE OF THE FIELD: Type 2 diabetes mellitus (T2DM) is increasingly
      prevalent throughout the world; controlling glycemia is an important part of
      preventing serious complications of diabetes. Sulfonylureas have been used in the
      treatment of type 2 diabetes for many years. AREAS COVERED IN THIS REVIEW: This
      article reviews the pharmacological and clinical aspects of glimepiride, a second
      generation sulfonylurea. Literature search was conducted in PubMed, and articles
      selected for relevance to pharmacology or clinical efficacy data from 1994 to
      2009, with older references sought as indicated. WHAT THE READER WILL GAIN:
      Pharmacology of glimepiride, data regarding clinical efficacy, key comparisons to
      other agents and emerging concepts related to glimepiride are discussed. TAKE
      HOME MESSAGE: Therapy with glimepiride improves the relative insulin secretory
      deficit found in T2DM, has antihyperglycemic efficacy equal to other
      secretagogues with reduced potential for hypoglycemia and may have additional
      actions contributing to glycemic control in T2DM.

PMID- 20055692
TI  - Correlation between plasma levels of apelin and myocardial hypertrophy in rats
      and humans: possible target for treatment?
AB  - OBJECTIVE: To investigate the effects of left ventricular (LV) pressure overload
      and diabetes on the apelinergic system. RESEARCH DESIGN/METHODS: Pressure
      overload was established in rats by supra-renal aortic-banding. Six weeks later,
      diabetes was induced by streptozotocin (65 mg/kg, intraperitoneal), resulting in
      four groups: sham, banded (BA), diabetic (DM) and diabetic-banded (DM-BA). Twelve
      weeks later, LV function and structure were evaluated by echocardiography and
      biopsies and plasma samples collected. Furthermore, plasma samples and LV
      endomyocardial biopsies were procured from aortic stenosis and mitral stenosis
      patients during surgery to evaluate myocardial expression of apelin and APJ
      receptor and plasma levels of apelin. RESULTS: Direct correlations between apelin
      plasma levels and LV-mass index and between apelin and APJ myocardial expression
      were observed both in humans and rats. Expression of apelin and APJ was not
      significantly altered by pressure-overload in humans, being downregulated by
      pressure overload and even more by diabetes in rats. Finally, an inverse
      correlation between apelin rat plasma levels and its myocardial expression was
      observed. CONCLUSIONS: While apelin/APJ myocardial expression decreases, apelin
      plasma levels increase in LV hypertrophy. Considering apelin's positive inotropic
      and vasodilator properties, this elevation in apelin plasma levels may represent
      a compensatory mechanism to maintain inotropism and cardiac output during
      pressure-overload or diabetic cardiomyopathy.

PMID- 20055693
TI  - The values of treatments for chronic inflammatory skin diseases; challenges of
      the market of health.

PMID- 20055694
TI  - Treatment of plaque psoriasis with the two-compound product
      calcipotriol/betamethasone dipropionate versus both monotherapies: an
      immunohistochemical study.
AB  - The combination of calcipotriol (Cp) and topical corticosteroids increases
      efficacy and reduces side effects as compared to monotherapies. Previous studies
      suggest that such combinations may have an added value with respect to reduction
      of T-cell subsets. A two-compound product consisting of Cp and betamethasone
      dipropionate (BD) has become available for the treatment of psoriasis and is
      clinically superior to both monotherapies. No immunohistochemical data are
      available on the in vivo effects of the two-compound formulation versus
      monotherapy with respect to the three key processes in psoriasis pathogenesis:
      epidermal proliferation, epidermal differentiation and inflammation. Therefore,
      18 patients were treated with the two-compound product, Cp monotherapy or BD
      monotherapy for 6 weeks and biopsies were taken before and after 4 and 6 weeks of
      treatment. These biopsies were stained immunohistochemically and analysed
      (semi)quantitatively. All treatments decreased the number of Ki-67(+) cells and
      increased the keratin 15(+) staining. A more pronounced reduction of epidermal
      and dermal T-cell markers and human beta defensin-2 was seen following
      combination treatment, compared with both monotherapies. In conclusion, the
      investigated markers of the skin immune system and epidermal proliferation
      indicated an added value of the two-compound product over both monotherapies.

PMID- 20055695
TI  - Treatment with twice-weekly tacrolimus ointment in patients with moderate to
      severe atopic dermatitis: results from two randomized, multicentre, comparative
      studies.
AB  - BACKGROUND: Twice-weekly tacrolimus ointment for mild to severe atopic dermatitis
      (AD) significantly reduced the number of flares and prolonged flare-free
      intervals compared with standard treatment in the CONTROL studies. METHODS: Post
      hoc analysis of data from the CONTROL studies was carried out on patients with
      moderate to severe disease. Patients applied tacrolimus 0.1% (adults; n = 183) or
      0.03% (children; n = 166) ointment twice-daily for <or= 6 weeks to treat flares,
      entering the 12-month disease control period (DCP) when an Investigator Global
      Assessment (IGA) score of <or= 2 was achieved. Patients were randomized to twice
      weekly tacrolimus or vehicle ointment. Disease flares were treated with twice
      daily tacrolimus ointment for 1-6 weeks until an IGA <or= 2 was achieved.
      RESULTS: Twice-weekly treatment significantly reduced the number of flares and
      time to first flare (p < 0.001). Around three times as many patients in each
      study had no flares of any severity throughout the double-blind period in the
      twice-weekly treatment group compared with the standard treatment group (p <
      0.001). Improvements in symptoms and quality of life with twice-weekly treatment
      were above those observed with standard treatment. Twice-weekly treatment was
      well tolerated. CONCLUSIONS: A twice-weekly tacrolimus ointment regimen was
      effective in adults and children with moderate to severe AD.

PMID- 20055696
TI  - Allosteric receptors: from electric organ to cognition.
AB  - This autobiography covers the past 50 years beginning with the development of the
      concept of allosteric proteins and its application to pharmacological receptors.
      It continues with the identification of the nicotinic acetylcholine receptor, the
      discovery of its molecular organization, the structure of the acetylcholine
      binding site and of the ion channel, and the demonstration of its allosteric
      transitions. The article then traces the origins of the concept of allosteric
      modulator and its consequences in pharmacology. It proceeds with the theory of
      selective stabilization of synapses and with experimental studies carried out on
      the contribution of the nicotinic receptor in the morphogenesis of the
      neuromuscular junction. The knowledge acquired with the nicotinic receptor is
      further exploited to reach higher levels of brain organization, and the
      contribution of nicotinic receptors to the action of nicotine on reward and
      cognition is explored, in particular, using a novel experimental strategy that
      combines nicotinic receptor genes knock-out and stereotaxic gene re-expression.
      Theoretical models of cognitive functions are proposed that link the molecular to
      the cognitive level. The report ends with a discussion on nicotinic receptors and
      the pharmacology of the future.

PMID- 20055697
TI  - Pharmacogenetics of drug dependence: role of gene variations in susceptibility
      and treatment.
AB  - Drug dependency is a highly prevalent mental health disorder that imposes a
      significant burden on those directly affected, health care systems, and society
      in general. There is substantial heritability in the susceptibility to drug
      addiction, which indicates that there are genetic risk factors. Variation in the
      human genome is abundant and can directly affect drug dependency phenotypes, for
      example, by altering the function of a gene product or by altering gene
      expression. Pharmacogenetic studies can assess the effects of genetic variation
      on the risk for a particular phenotype (e.g., being an alcoholic). In addition,
      pharmacogenetic variability in treatment efficacy and adverse reactions can be
      investigated to identify particular genetic variants associated with altered
      responses. This review highlights examples of genetic variations that are
      important in the development and maintenance of specific drug dependencies as
      well as those that affect the response to treatment.

PMID- 20055698
TI  - Close encounters of the small kind: adverse effects of man-made materials
      interfacing with the nano-cosmos of biological systems.
AB  - Engineered nanomaterials have unique physico-chemical properties that make them
      promising for many technological and biomedical applications, including tissue
      regeneration, drug and gene delivery, and in vivo monitoring of disease
      processes. However, with the burgeoning capabilities to manipulate structures at
      the nano-scale, intentional as well as unintentional human exposures to
      engineered nanomaterials are set to increase. Nanotoxicology is an emerging
      discipline focused on understanding the properties of engineered nanomaterials
      and their interactions with biological systems, and may be viewed as the study of
      the undesirable interference between man-made nanomaterials and cellular
      nanostructures or nanomachines. In this review, we discuss recognition of
      engineered nanomaterials by the immune system, our primary defense system against
      foreign invasion. Moreover, as oxidative stress is believed to be one of the
      major deleterious consequences of exposure to nanomaterials, we explore
      triggering of pro- and antioxidant pathways as well as biomarkers of oxidative
      stress. Finally, we highlight in vivo studies of the toxicological outcomes of
      engineered nanomaterials, including carbon nanotubes, with an emphasis on
      inflammation and genotoxic responses.

PMID- 20055699
TI  - GPCR interacting proteins (GIPs) in the nervous system: Roles in physiology and
      pathologies.
AB  - G protein-coupled receptors (GPCRs) are key transmembrane recognition molecules
      for regulatory signals such as light, odors, taste hormones, and
      neurotransmitters. In addition to activating guanine nucleotide binding proteins
      (G proteins), GPCRs associate with a variety of GPCR-interacting proteins (GIPs).
      GIPs contain structural interacting domains that allow the formation of large
      functional complexes involved in G protein-dependent and -independent signaling.
      At the cellular level, other functions of GIPs include targeting of GPCRs to
      subcellular compartments and their trafficking to and from the plasma membrane.
      Recently, roles of GPCR-GIP interactions in central nervous system physiology and
      pathologies have been revealed. Here, we highlight the role of GIPs in some
      important neurological and psychiatric disorders, as well as their potential for
      the future development of therapeutic drugs.

PMID- 20055700
TI  - The RNA polymerase I transcription machinery: an emerging target for the
      treatment of cancer.
AB  - The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key
      convergence point that collects and integrates a vast array of information from
      cellular signaling cascades to regulate ribosome production that in turn guides
      cell growth and proliferation. Cancer cells commonly harbor mutations that
      inactivate tumor suppressors, hyperactivate oncogenes, and upregulate protein
      kinases, all of which promote Pol I transcription and drive cell proliferation.
      The intimate balance between Pol I transcription and growth-factor signaling is
      perturbed in cancer cells, indicating that upregulation of rRNA synthesis is
      mandatory for all tumors. Though the emerging picture of transcriptional
      regulation reveals an unexpected level of complexity, we are beginning to
      understand the multiple links between rRNA biogenesis and cancer. In this review,
      we discuss experimental data and potential strategies to downregulate rRNA
      synthesis and induce an antiproliferative response in cancer cells.

PMID- 20055701
TI  - LPA receptors: subtypes and biological actions.
AB  - Lysophosphatidic acid (LPA) is a small, ubiquitous phospholipid that acts as an
      extracellular signaling molecule by binding to and activating at least five known
      G protein-coupled receptors (GPCRs): LPA(1)-LPA(5). They are encoded by distinct
      genes named LPAR1-LPAR5 in humans and Lpar1-Lpar5 in mice. The biological roles
      of LPA are diverse and include developmental, physiological, and
      pathophysiological effects. This diversity is mediated by broad and overlapping
      expression patterns and multiple downstream signaling pathways activated by
      cognate LPA receptors. Studies using cloned receptors and genetic knockout mice
      have been instrumental in uncovering the significance of this signaling system,
      notably involving basic cellular processes as well as multiple organ systems such
      as the nervous system. This has further provided valuable proof-of-concept data
      to support LPA receptors and LPA metabolic enzymes as targets for the treatment
      of medically important diseases that include neuropsychiatric disorders,
      neuropathic pain, infertility, cardiovascular disease, inflammation, fibrosis,
      and cancer.

PMID- 20055702
TI  - The role of clock genes in pharmacology.
AB  - The physiology of a wide variety of organisms is organized according to periodic
      environmental changes imposed by the earth's rotation. This way, a large number
      of physiological processes present diurnal rhythms regulated by an internal
      timing system called the circadian clock. As part of the rhythmicity in
      physiology, drug efficacy and toxicity can vary with time. Studies over the past
      four decades present diurnal oscillations in drug absorption, distribution,
      metabolism, and excretion. On the other hand, diurnal variations in the
      availability and sensitivity of drug targets have been correlated with time
      dependent changes in drug effectiveness. In this review, we provide evidence
      supporting the regulation of drug kinetics and dynamics by the circadian clock.
      We also use the examples of hypertension and cancer to show current achievements
      and challenges in chronopharmacology.

PMID- 20055703
TI  - Toxicological disruption of signaling homeostasis: tyrosine phosphatases as
      targets.
AB  - The protein tyrosine phosphatases (PTPs) consist of a diverse group of enzymes
      whose activity opposes that of the tyrosine kinases. As such, the PTPs have
      critical roles in maintaining signaling quiescence in resting cells and in
      restoring homeostasis by effecting signal termination. Interest in these enzymes
      has increased in recent years following the discovery that the activity of PTPs
      is modulated through redox mechanisms during signaling. The molecular features
      that enable redox regulation of PTPs during physiological signaling also render
      them highly susceptible to oxidative and electrophilic inactivation by a broad
      spectrum of structurally disparate xenobiotic compounds. The loss of PTP activity
      results in a profound disregulation of protein phosphotyrosine metabolism,
      leading to widespread and persistent activation of signaling cascades in the
      cell.

PMID- 20055704
TI  - Discovery and development of therapeutic aptamers.
AB  - Therapeutic aptamers are single-stranded structured oligonucleotides that bind to
      protein targets with high affinity and specificity and modulate protein function.
      Aptamers are discovered by iterative rounds of selection for binding to the
      target protein, partitioning, and amplification of binding clones from a diverse
      starting library (SELEX). Postselection optimization of clones using chemical
      modification is directed at improving affinity, potency, and metabolic stability.
      A key attribute of therapeutic aptamers is the ability to tailor the
      pharmacokinetic profile by modulating the degree of metabolic stability and
      modulating renal clearance and rate of distribution by conjugation to various
      sizes of polyethylene glycol (PEG). In toxicology studies, therapeutic aptamers
      have been largely devoid of the previously reported oligonucleotide class effects
      of immune stimulation, complement activation, and anticoagulation; and the
      principal finding is the histologically visible accumulation of drug-related
      material in mononuclear phagocytes, a finding generally not considered an adverse
      effect. Good safety margins between the pharmacologically effective dose and
      toxicologically established no-adverse-effect levels have been observed
      consistently. There are presently seven aptamers either on the market or in
      clinical trials, but there is still much to be demonstrated in terms of chronic
      systemic use to fully realize the potential of this promising new class of drugs.

PMID- 20055705
TI  - RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as
      a therapeutic platform.
AB  - Dramatic advances in understanding of the roles RNA plays in normal health and
      disease have greatly expanded over the past 10 years and have made it clear that
      scientists are only beginning to comprehend the biology of RNAs. It is likely
      that RNA will become an increasingly important target for therapeutic
      intervention; therefore, it is important to develop strategies for
      therapeutically modulating RNA function. Antisense oligonucleotides are perhaps
      the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides
      are designed to bind to the target RNA by well-characterized Watson-Crick base
      pairing, and once bound to the target RNA, modulate its function through a
      variety of postbinding events. This review focuses on the molecular mechanisms by
      which antisense oligonucleotides can be designed to modulate RNA function in
      mammalian cells and how synthetic oligonucleotides behave in the body.

PMID- 20055707
TI  - Mechanisms of cell protection by heme oxygenase-1.
AB  - Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin
      (IX), into equimolar amounts of Fe(2+), carbon monoxide (CO), and biliverdin. The
      stress-responsive HO-1 isoenzyme affords protection against programmed cell
      death. The mechanism underlying this cytoprotective effect relies on the ability
      of HO-1 to catabolize free heme and prevent it from sensitizing cells to undergo
      programmed cell death. This cytoprotective effect inhibits the pathogenesis of a
      variety of immune-mediated inflammatory diseases.

PMID- 20055708
TI  - Epac: defining a new mechanism for cAMP action.
AB  - cAMP is a second messenger that is essential for relaying hormonal responses in
      many biological processes. The discovery of the cAMP target Epac explained
      various effects of cAMP that could not be attributed to the established targets
      PKA and cyclic nucleotide-gated ion channels. Epac1 and Epac2 function as guanine
      nucleotide exchange factors for the small G protein Rap. cAMP analogs that
      selectively activate Epac have helped to reveal a role for Epac in processes
      ranging from insulin secretion to cardiac contraction and vascular permeability.
      Advances in the understanding of the activation mechanism of Epac and its
      regulation by diverse anchoring mechanisms have helped to elucidate the means by
      which cAMP fulfills these functions via Epac.

PMID- 20055706
TI  - Metabotropic glutamate receptors: physiology, pharmacology, and disease.
AB  - The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled
      receptors that participate in the modulation of synaptic transmission and
      neuronal excitability throughout the central nervous system. The mGluRs bind
      glutamate within a large extracellular domain and transmit signals through the
      receptor protein to intracellular signaling partners. A great deal of progress
      has been made in determining the mechanisms by which mGluRs are activated,
      proteins with which they interact, and orthosteric and allosteric ligands that
      can modulate receptor activity. The widespread expression of mGluRs makes these
      receptors particularly attractive drug targets, and recent studies continue to
      validate the therapeutic utility of mGluR ligands in neurological and psychiatric
      disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression,
      and schizophrenia.

PMID- 20055709
TI  - Economic opportunities and challenges for pharmacogenomics.
AB  - Economic evaluation provides health care decision makers with a powerful tool for
      resource allocation decisions because it offers a framework for comparing the
      costs and benefits of competing interventions or options. This paper reviews how
      economic analyses have been applied to the field of pharmacogenomics, both by the
      pharmaceutical industry to inform investment decisions and by payers to make
      coverage decisions. There is much anticipation that pharmacogenomic testing is
      likely to be cost-effective because it uses genomic information to improve drug
      effectiveness and reduce toxicity both in the drug development process and at the
      bedside. However, the demonstration of economic benefits first requires that
      pharmacogenomic testing show evidence of clinical effectiveness. This will only
      be achieved by greater participation of pharmacogenomics experts in comparative
      effectiveness research and additional emphasis on including costs in the
      determination of the relative value of pharmacogenomic testing to the health care
      system.

PMID- 20055710
TI  - Tissue renin-angiotensin-aldosterone systems: Targets for pharmacological
      therapy.
AB  - The renin-angiotensin-aldosterone system is one of the most important systems in
      cardiovascular control and in the pathogenesis of cardiovascular diseases.
      Therefore, it is already a very successful drug target for the therapy of these
      diseases. However, angiotensins are generated not only in the plasma but also
      locally in tissues from precursors and substrates either locally expressed or
      imported from the circulation. In most areas of the brain, only locally generated
      angiotensins can exert effects on their receptors owing to the blood-brain
      barrier. Other tissue renin-angiotensin-aldosterone systems are found in
      cardiovascular organs such as kidney, heart, and vessels and play important roles
      in the function of these organs and in the deleterious actions of hypertension
      and diabetes on these tissues. Novel components with mostly opposite actions to
      the classical renin-angiotensin-aldosterone systems have been described and need
      functional characterization to evaluate their suitability as novel drug targets.

PMID- 20055711
TI  - Cost-effectiveness of a hydroquinone/tretinoin/fluocinolone acetonide cream
      combination in treating melasma in the United States.
AB  - BACKGROUND: Melasma, a disorder of facial hyperpigmentation, presents a treatment
      obstacle to many physicians. Combination therapy with hydroquinone, tretinoin,
      and fluocinolone acetonide has proven effective, but it is generally more
      expensive than other treatments. OBJECTIVE: To assess the cost-effectiveness of
      daily triple combination therapy (TCT) compared with daily use of each possible
      pair of agents (dyads) and twice daily use of hydroquinone (HQ) alone from a
      payer's perspective. METHODS: Efficacy data were obtained from two clinical
      trials with the primary endpoint being complete clearance at 8 weeks. For all
      treatments, total cost per successful treatment was calculated. The incremental
      cost-effectiveness ratio (ICER) was calculated for each dyad and for HQ
      monotherapy in comparison with TCT. Sensitivity analyses for efficacy and number
      of office visits were similarly performed. RESULTS AND CONCLUSION: TCT
      consistently had the lowest cost per primary success in all the analyses
      performed. Furthermore, ICERs were low, indicating that TCT's superior efficacy
      is attained at marginal cost increases. Our results indicate that TCT is the most
      cost-effective treatment when compared with any of its dyads or with hydroquinone
      alone.

PMID- 20055712
TI  - Pseudomonas aeruginosa biofilm infections in cystic fibrosis: insights into
      pathogenic processes and treatment strategies.
AB  - IMPORTANCE OF THE FIELD: CF airway mucus can be infected by opportunistic
      microorganisms, notably Pseudomonas aeruginosa. Once organisms are established as
      biofilms, even the most potent antibiotics have little effect on their viability,
      especially during late-stage chronic infections. Better understanding of the
      mechanisms used by P. aeruginosa to circumvent host defenses and therapeutic
      intervention strategies is critical for advancing novel treatment strategies.
      AREAS COVERED IN THIS REVIEW: Inflammatory injury in CF lung, role of neutrophils
      in pathogenesis, P. aeruginosa biofilms, mucoidy and its relationship with poor
      airway oxygenation, mechanisms by which P. aeruginosa biofilms in the CF airway
      can be killed. WHAT THE READER WILL GAIN: An understanding of the processes that
      P. aeruginosa undergoes during CF airway disease and clues to better treat such
      infections in future. TAKE HOME MESSAGE: The course of CF airway disease is a
      process involving host and microbial factors that often dictate frequency of
      pulmonary exacerbations, thus affecting the overall course. In the past decade
      significant discoveries have been made regarding the pathogenic processes used by
      P. aeruginosa to bypass the immune system. Many new and exciting features of P.
      aeruginosa now illuminate weaknesses in the organism that may render it
      susceptible to inexpensive compounds that force its own destruction.

PMID- 20055713
TI  - Immunomodulatory role of thymulin in lung diseases.
AB  - IMPORTANCE OF THE FIELD: Inflammation is a hallmark of lung diseases. The
      available treatment options are unsatisfactory because they are not efficacious
      or induce major side effects. Alternative approaches need to be developed.
      Thymulin is a peptide exclusively produced in the thymus with several anti
      inflammatory properties. AREAS COVERED IN THIS REVIEW: The physiological features
      of thymulin and data that support its potential as an anti-inflammatory treatment
      for lung diseases are reviewed. WHAT THE READER WILL GAIN: Thymulin has
      consistent beneficial effects in experimental models of lung diseases. It has a
      broad inhibitory effect on pro-inflammatory cytokines, suppresses p38 (a MAPK
      family member) and inhibits the activation of the NF-kappaB signal pathway. It is
      an attractive peptide for lung gene therapy because has no toxicity even at high
      doses and when expressed by adenoviral vectors reduces immune response against
      viral proteins. TAKE HOME MESSAGE: Thymulin has a selective immunomodulatory
      effect, enhancing anti-inflammatory and inhibiting pro-inflammatory cytokines. It
      suppresses p38 (implicated in glucocorticoid-resistance) and inhibits NF-kappaB
      activation, which has an important pathogenic role in several lung diseases. The
      broad spectrum of anti-inflammatory effects of this peptide in several animal
      models of lung disease makes thymulin a good candidate for future clinical
      trials.

PMID- 20055715
TI  - Targeting CCL11 in the treatment of ovarian cancer.
AB  - IMPORTANCE OF THE FIELD: The chemokine network, comprised of mediators of
      inflammation, has been implicated in the development of a number of human
      cancers. The eosinophil chemoattractant CCL11 was recently shown to play a role
      in the development of ovarian cancer. Here we review findings regarding CCL11 and
      discuss its use as a target in the treatment of ovarian cancer. AREAS COVERED IN
      THIS REVIEW: We review published findings related to the physiological actions of
      CCL11, its tumourigenic effects, the chemokine network and inflammatory response
      present in ovarian cancer, and the current state of therapeutics targeting CCL11
      and its receptors. Findings published within the last 10 years receive particular
      attention. WHAT THE READER WILL GAIN: An overview of the emerging role of the
      chemokine network in malignancy and a review of the role of CCL11 in ovarian
      tumourigenesis. The reader will be presented with a description of the unique
      aspects of CCL11 action and the inflammatory environment in the setting of
      ovarian malignancy that make this chemokine an attractive target for
      intervention. TAKE HOME MESSAGE: Targeting CCL11 and its receptors through the
      use of monoclonal antibodies and small-molecule inhibitors may represent a
      beneficial new avenue of ovarian cancer treatment.

PMID- 20055714
TI  - Vascular KCa-channels as therapeutic targets in hypertension and restenosis
      disease.
AB  - IMPORTANCE OF THE FIELD: Cardiovascular disease is a leading cause of death in
      modern societies. Hyperpolarizing Ca(2+)-activated K(+) channels (K(Ca)) are
      important membrane proteins in the control of arterial tone and pathological
      vascular remodelling and thus could serve as new drug targets. AREAS COVERED IN
      THIS REVIEW: We summarize recent advances in the field of vascular K(Ca) and
      their roles in cardiovascular pathologies such as hypertension and restenosis
      disease and draw attention to novel small-molecule channel modulators and their
      possible therapeutic utility. This review focuses on literature from the last
      four to five years. WHAT THE READER WILL GAIN: Pharmacological opening of
      endothelial KCa3.1/KCa2.3 channels stimulates endothelium-derived-hyperpolarizing
      factor-mediated arteriolar dilation and lowers blood pressure. Inhibition of
      smooth muscle KCa3.1 channels has beneficial effects in restenosis disease and
      atherosclerosis. We consider the therapeutic potential of KCa3.1/KCa2.3 openers
      as novel endothelium-specific antihypertensive drugs as well as of KCa3.1
      blockers for the treatment of pathological vascular remodelling and discuss
      advantages and disadvantages of the pharmacotherapeutic approaches. TAKE HOME
      MESSAGE: Pharmacological manipulation of vascular K(Ca) channels by novel small
      molecule modulators offers new venues for alternative treatments of hypertension,
      restenosis and atherosclerosis. Additional efforts are required to optimize these
      compounds and to validate them as cardiovascular-protective drugs.

PMID- 20055716
TI  - Targeting DAX-1 in embryonic stem cells and cancer.
AB  - IMPORTANCE OF THE FIELD: DAX-1 (NR0B1) is an unusual orphan nuclear receptor
      whose function is essential for the development of the human adrenal cortex and
      onset of puberty. Recent data have implicated this transcription factor also in
      embryonic stem cell and cancer biology. AREAS COVERED IN THIS REVIEW: The role of
      DAX-1 in the regulation of development and function of the adrenal cortex,
      reproductive axis, embryonic stem cells and a few types of cancer. WHAT THE
      READER WILL GAIN: Here we review the past and present milestones in DAX-1
      research and try to provide hints about the development and fields of application
      of DAX-1-targeted drugs in the future. TAKE HOME MESSAGE: The unusual structure
      and restricted expression pattern of DAX-1 may offer unique opportunities for
      drug discovery.

PMID- 20055717
TI  - TGF-beta signalling and immunity in prostate tumourigenesis.
AB  - IMPORTANCE OF THE FIELD: The TGF-beta's are pleiotropic cytokines that regulate
      multiple cellular functions. Their role in the prostate is important for normal
      prostate development and also in prostate tumourigenesis. AREAS COVERED IN THIS
      REVIEW: The interactions TGF-beta-mediated signalling has with maintaining
      prostate health, as well as its role in prostate tumourigenesis and prostate
      tumour immune evasion, with emphasis on how a breakdown in these interactions may
      influence disease progression. WHAT THE READER WILL GAIN: That TGF-beta
      influences normal prostate growth and differentiation by regulating the balance
      between epithelial cell proliferation and apoptosis, and involving the androgen
      receptor pathway. That TGF-beta protects and maintains prostate stem cells and a
      review of the contrasting role TGF-beta has in prostate tumourigenesis and tumour
      development, where TGF-beta acts as a tumour suppressor and then switches roles
      to become a tumour promoter, and creates a local immunosuppressive niche leading
      to systemic tumour tolerance. TAKE HOME MESSAGE: TGF-beta signalling in prostate
      cancer is a valid target for the treatment of this disease; however any
      therapeutic regimen will require an understanding of all aspects of the TGF-beta
      signalling nexus, otherwise by the very pleiotrophic nature of TGF-beta, limited
      clinical benefits may result.

PMID- 20055718
TI  - Fractalkine/CX3CR1: why a single chemokine-receptor duo bears a major and unique
      therapeutic potential.
AB  - IMPORTANCE OF THE FIELD: Fractalkine, also known as CX3CL1, is the unique member
      of the fourth class of chemokines and mediates both chemotaxis and adhesion of
      inflammatory cells via its highly selective receptor CX3CR1. Fractalkine mediates
      inflammatory responses and pain sensation and is involved in the pathogenesis and
      progression of numerous inflammatory disorders and malignancies. AREAS COVERED IN
      THIS REVIEW: We performed a Medline/PubMed search to detect all published studies
      that explored the role of fractalkine and CX3CR1 and the possibilities of
      therapeutic intervention in the fractalkine/CX3CR1 axis in a wide range of
      clinical disorders, using CX3CR1 blocking antibodies, different fractalkine
      antagonists, CX3CR1 depletion or transfection of fractalkine expression vectors.
      WHAT THE READER WILL GAIN: This review summarizes the role of fractalkine and its
      receptor CX3CR1 in various diseases, focusing on their high potential as novel
      therapeutic targets, with special emphasis on pancreatic diseases. TAKE HOME
      MESSAGE: The reviewed studies provide promising results demonstrating fractalkine
      and CX3CR1 as potential target molecules for future therapeutics that may
      attenuate pain, inflammation and furthermore serve as an anti-cancer therapy.
      However, to date, no therapeutics targeting fractalkine or CX3CR1 are in clinical
      use.

PMID- 20055719
TI  - Dickkopf-1 as a potential therapeutic target in Paget's disease of bone.
AB  - IMPORTANCE OF THE FIELD: Wnt signalling plays a role in maintaining healthy bone
      mass. Dickkopf-1 (DKK-1) is a soluble inhibitor of Wnt signalling and its
      excessive expression contributes to bone loss in rheumatoid arthritis and
      multiple myeloma. New therapeutics have been developed for treatment of these
      conditions that target DKK-1 expression. DKK-1 is elevated in serum of patients
      with Paget's disease of the bone (PDB) and evidence is accumulating for a role of
      DKK-1 in PDB. AREAS COVERED IN THIS REVIEW: The role of Wnt signalling and DKK-1
      in bone health and disease and the aetiology of PDB in the light of recent
      advances in understanding of Wnt signalling. WHAT THE READER WILL GAIN: PDB is a
      disorder of unknown aetiology characterised by localised increase in unregulated
      bone remodelling resulting in osteolytic and osteosclerotic lesions. Evidence is
      adduced for the involvement of Wnt signalling, DKK-1 and osteoblasts in PDB
      pathogenesis. TAKE HOME MESSAGE: At present there is no cure for PDB and the
      current treatment of choice are bisphosphonates. These treat the resorptive phase
      of PDB but do not prevent its return. We present a new perspective on the
      aetiology of PDB and speculate on DKK-1 as a therapeutic target.

PMID- 20055720
TI  - Validity and reliability of the Turkish version of the Hill-Bone compliance to
      high blood pressure therapy scale for use in primary health care settings.
AB  - OBJECTIVES: To assess the validity and reliability of the Turkish version of the
      Hill-Bone compliance to high blood pressure therapy scale for use in primary care
      in Turkey. METHODS: To develop a Turkish version of the scale, it was translated
      into Turkish then back-translated into English. The final version was used in a
      survey in two urban primary health care centers in Izmir, Turkey. For assessing
      the validity of Turkish scale, we performed factor analysis to test construct
      validity. Reliability was assessed by calculating the Cronbach's alpha as a
      measure of internal consistency. RESULTS: Factor analysis revealed a three-factor
      structure representing unintentional medication non-adherence; intentional
      medication non-adherence; and salt intake adherence. Percentages of explained
      variance were 33.3%, 14.6% and 11.2% respectively. When forcing a two-factor
      structure we found salt intake and medication adherence clusters. Cronbach's
      alpha was 0.72 and 0.83 for medication adherence and whole scale, respectively.
      CONCLUSION: The Turkish Hill-Bone scale presented a factor structure consistent
      with the original scale, had a high level of internal consistency. It can be used
      for assessing hypertension patients' compliance in Turkish primary care settings.

PMID- 20055721
TI  - Patient attitudes towards and experiences with an intervention programme to
      reduce chronic acid-suppressing drug intake in primary care.
AB  - OBJECTIVE: Many patients are using acid-suppressing drugs (ASD) unnecessary. An
      insurance company initiated intervention programme aiming at reduction of chronic
      ASD use, was introduced in primary care-practices. We evaluated the attitude and
      experiences of the participating patients. METHODS: A survey was conducted among
      a random sample of 2376 long-term ASD users using a validated questionnaire that
      combined CAHPS and QUOTE methodology. Using a psychometric principal component
      analysis we assessed the role of GPs in three scales: quality of support;
      communication and conduct; involvement in decisions. Both the importance of and
      experiences with quality items, transformed into quality impact indices, were
      measured. RESULTS: Of 2376 questionnaires distributed, 1808 (76%) were returned,
      1270 (54%) were valid. 188 were of patients that participated in the programme.
      The majority was dissatisfied with the GPs' support: no information about rebound
      side effects (76%), lifestyle habits (68%), and reasons to stop (50%). Compared
      to the non-participants 9% more participants stopped ASD use (P = 0.04).
      CONCLUSION: A majority of patients on chronic ASD was prepared to participate in
      the drug-reduction programme. Although 16% succeeded in stopping ASD use, the
      majority was dissatisfied with the role of the GP. Improved GP support might have
      make more patients stop using ASD.

PMID- 20055722
TI  - Obtaining the family history for common, multifactorial diseases by family
      physicians. A descriptive systematic review.
AB  - OBJECTIVE: To summarize the knowledge on the use of comprehensive family history
      taking for common, multifactorial diseases in primary health care. DESIGN AND
      DATA SOURCES: Systematic review of MEDLINE (1966-2008), EMBASE (1986-2008) and
      Cochrane Library. METHODS: Search terms reflected 'primary care', 'family
      history' and 'genetics'. Included were original studies, published in the English
      language, from a primary care setting, investigating family history taking for
      multifactorial disorders. Methodological criteria (design, size, response rate)
      were not used to exclude papers. Out of 116 potentially eligible papers, 27
      papers were selected: nine studies on opinions, eight studies on actual practice,
      seven studies on family history tools, and three studies on the patient
      perspective. Two authors independently extracted the data, and consequently
      discussed and summarized them. Given the heterogeneity of the studies, outcomes
      were presented in a qualitative way. RESULTS: Among family physicians, the
      general opinion was that taking a family history is the task of the primary care
      physician. However, observational studies of consultations and analyses of
      medical records showed wide variability and low regular updating. There are no
      family history tools yet, that are sufficiently feasible and reproducible.
      Patients and doctors may perceive a positive family history differently, which
      may cause miscommunication. CONCLUSION: There is a need for research into
      feasible and high quality tools for detailed family history taking for
      multifactorial disorders.

PMID- 20055723
TI  - The Research Agenda for General Practice/Family Medicine and Primary Health Care
      in Europe. Part 1. Background and methodology.
AB  - At the WONCA Europe conference 2009 the recently published 'Research Agenda for
      General Practice/Family Medicine and Primary Health Care in Europe' was
      presented. The Research Agenda is a background paper and reference manual for
      GPs/ family doctors, researchers and policy makers, providing advocacy of general
      practice/family medicine GP/FM in Europe. The Research Agenda summarizes the
      evidence relating to the core competencies and characteristics of the WONCA
      Europe definition of GP/FM, and its meaning for researchers and policy makers.
      Evidence gaps and research needs are pointed out to provide a basis for planning
      research for which there is a need and for action that may influence health and
      research policy, i.e. applying/lobbying for research funds. WONCA Europe and its
      associated networks and special interest groups could consider the agenda's
      research priorities when planning future conferences, courses, or projects, and
      for funding purposes. The European Journal of General Practice will publish a
      series of articles based on this document. In this first article, background,
      objectives, methodology and relevant literature are discussed. In subsequent
      articles, the results will be presented.

PMID- 20055724
TI  - Varicella-zoster virus pneumonia in an adult population: has mortality decreased?
AB  - Varicella-zoster virus (VZV) pneumonia is one of the most serious complications
      of this infection in adults. The objective of this study was to analyze the
      epidemiological and clinical characteristics in a large sample of patients with
      VZV pneumonia. This was a 10-y retrospective, descriptive, observational study.
      We studied 46 patients with VZV pneumonia, 21 men and 25 women, with a mean age
      36 +/-11 y. A contact with an index case was observed in 57%, 76 were active
      smokers, 6.5% consumed drugs and 2 women were pregnant. The symptoms were: fever
      (83%), cough (83%), dyspnoea (63%), pleuritic pain (70%), and haemoptysis (6%)
      and started 3-5 days after the onset of blisters, except in 11% in whom
      respiratory symptoms appeared first. Arterial blood gases showed a mean
      PO(2)/FiO(2) of 308 +/-101 and 30 patients had a PO(2) of <55 mmHg--11 of these
      (4%) were admitted to the ICU, 8 required mechanical ventilation. Comparison of
      patients in the ICU with those on the general ward showed differences in the
      duration of fever (6.1 +/- 4.2 vs 3.2 +/- 1.1 days, p <0.001), mean stay (16.8+/
      9.3 vs 7.2+/-2.4 days, p <0.001) and complications such as acute renal failure (p
      = 0.01) and acute respiratory failure (p < 0.001). Despite the severity of
      disease, no patient died. Once diagnosed, 98% were treated with acyclovir,
      combined with steroids in 6 and with antibiotics in 3 complicated with bacterial
      pneumonia. The prevalence for the period was 0.33 cases/100,000 inhabitants/y. In
      conclusion, VZV pneumonia has a severe course and accounts for a high percentage
      of admissions to the intensive care unit. The absence of mortality may be related
      to early treatment with acyclovir. Smoking was a risk factor for VZV pneumonia.

PMID- 20055725
TI  - Candida albicans prosthetic hip infection in elderly patients: is fluconazole
      monotherapy an option?
AB  - The increasing numbers of joint arthroplasties being undertaken, and the increase
      in patients with systemic illnesses undergoing the procedure, have contributed to
      a continuing increase in prosthetic joint infections. Candida prosthetic joint
      infection is a rare clinical entity, and only 12 cases of Candida albicans
      prosthetic hip infection have been described. Although surgery combined with a
      long period of antifungal medication is the usual treatment for fungal prosthetic
      joint infections, monotherapy with antifungal agents has only very rarely been
      used as a therapeutic option, especially in debilitated and elderly patients. We
      report herein the second case, to our knowledge, of C. albicans prosthetic hip
      arthritis successfully treated with fluconazole monotherapy and review the
      literature on the pathogenesis, clinical manifestations and management of these
      infections. Further studies on the use of fluconazole in the management of fungal
      prosthetic infections are needed.

PMID- 20055726
TI  - Interferon-gamma gene and interferon-gamma receptor-1 gene polymorphisms in
      children with tuberculosis from Turkey.
AB  - Macrophage activation by interferon-gamma (IFN-gamma) is important in host
      resistance to tuberculosis (TB). In this study, the relationships of the +874 T/A
      polymorphism in the first intron of the IFN-gamma gene and intronic (CA)n
      polymorphic microsatellite marker of the interferon-gamma receptor 1 (IFN
      gammaR1) gene to TB susceptibility were investigated in children. Forty children
      with TB and 67 age-matched controls were included. There were no significant
      differences between the allele frequencies and genotype frequencies of patient
      and control groups for the polymorphism +874 T/A in the IFN-gamma gene.
      Differences that were not statistically significant were found between the group
      of children with TB and the control group for the allelic markers (170 and 180)
      in the IFN-gammaR1 gene. The incidence of the allele 170 was higher in patients
      (30.9%) than in controls (17.4%), whereas the allele 180 was found to be more
      common in controls (9% vs 1.2%). In conclusion, no significant association was
      observed between the +874 T/A polymorphism found in the first exon of the IFN
      gamma gene and TB susceptibility in Turkish children.

PMID- 20055727
TI  - Antimicrobial susceptibility of clinical Campylobacter isolates collected at a
      German university hospital during the period 2006-2008.
AB  - A total of 113 clinical Campylobacter strains (105 C. jejuni, 7 C. coli, 1 C.
      lari) were collected between 2006 and 2008 and tested for antimicrobial
      susceptibility to erythromycin, ciprofloxacin, doxycycline and meropenem. Of all
      the Campylobacter isolates, 52.2% were resistant to ciprofloxacin and 38.0% to
      doxycycline. None of them was resistant to erythromycin or meropenem. However,
      51.3% of all Campylobacter isolates were intermediate susceptible to erythromycin
      (minimum inhibitory concentration 1-4 mg/l). These data confirm the value of
      macrolides as the drugs of choice for the treatment of severe Campylobacter
      infections.

PMID- 20055728
TI  - A community-based vasectomy service in Leicestershire and Rutland - The patients'
      perspective.
AB  - OBJECTIVES: To evaluate the community-based vasectomy service from the patients'
      perspective and consider service provision in terms of access, process, quality
      and outcome. METHOD: A prospective questionnaire was handed to 150 consecutive
      men attending for vasectomy from February to June 2007, for completion two weeks
      after surgery. Postal reminders were sent at four and eight weeks. RESULTS: The
      response rate was 73%, with 93% (n = 102) of the respondents considering the
      vasectomy unit to be of high quality. The comprehension of written information
      (93%) and the approachability of staff (83%) were both considered highly
      satisfactory. Most men were equivocal regarding proposed 'holistic' changes to
      the service. Men under 40 were more likely to be neutral or agree that vasectomy
      was embarrassing and preferred a male surgeon. The occurrence of complications
      did not affect satisfaction but increased the mean number of disturbed nights
      sleep and days taking analgesia. Suggestions for improvement pertained to the pre
      operative information and the use of skin sutures. CONCLUSIONS: The patients'
      evaluation of our vasectomy unit identified areas for improvement and reinforced
      good clinical practice. More research is needed to clarify the impact of age,
      ethnicity and other factors on the accessibility, acceptability and experience of
      vasectomy.

PMID- 20055729
TI  - State-of-the-art of non-hormonal methods of contraception: II. Chemical barrier
      contraceptives.
AB  - Chemical contraceptives mainly known as spermicides are one of the oldest types
      of contraceptives. The industrial revolution facilitated new developments, and
      they became a leading and widespread method. However, their use declined in the
      second half of the 20th century, and came under focus again only with the upsurge
      of sexually transmitted infections (STIs). The effectiveness of spermicides
      depends on the users' compliance and pregnancy rates vary widely: from 6/100
      woman-year (with perfect use) to 26/100 woman-year (with typical use).
      Preparations consist of two components: an excipient (foam, cream, jelly, soluble
      film, suppository or tablet); and a chemical agent with spermicidal properties
      (acidic compound, microbicidal agent, detergent). The most widely used active
      agent has been the surface active (detergent) nonoxynol-9 (N-9). Based on their
      mode of action (surfactant effect of detergents, enzymatic action of microbicides
      on cell metabolism) spermicides were thought to provide protection against STIs
      including HIV. Recent studies have, however, shown that detergents may actually
      increase the risk. Because of this, there is an urgent need for a suitable non
      detergent spermicide, and research should focus on developing new compounds to
      replace N-9 and other agents having similar undesired effects. This paper reviews
      the latest studies reporting results on these recent developments.

PMID- 20055730
TI  - Pre-treatment patient variables as predictors of drop-out and treatment outcome
      in cognitive behavioural therapy for social phobia: A systematic review.
AB  - BACKGROUND: Although cognitive behavioural therapy (CBT) has been shown to be an
      efficacious treatment for social phobia (SP), many patients drop out or achieve
      little or no benefit from treatment. This fact is generally considered an
      argument for the importance of studies of predictor variables. AIMS: This paper
      systematically reviews pre-treatment patient variables as predictors of drop-out
      from and outcome of CBT for SP. METHOD: A structured literature search was
      conducted in PsycINFO, Embase and PubMed. RESULTS: 28 published studies with
      n>or=60 were located. No pre-treatment patient variables were found to predict
      drop-out. Consistently across studies, higher levels of pre-treatment symptomatic
      severity predicted higher levels of end-state symptomatic severity, but not
      degree of improvement. There was some evidence that comorbid depression and
      avoidant personality disorder before treatment negatively influenced post
      treatment end-state functioning, but not consistently improvement. No other
      patient variables consistently predicted outcome across studies. CONCLUSIONS:
      Generally, the results are in line with the conclusion that more disturbed
      patients with SP both begin and end treatment at a higher symptomatic level but
      with a similar degree of improvement. There is, however, little clinically or
      theoretically relevant knowledge to be gained from existing studies of pre
      treatment patient variables as predictors of drop-out and treatment outcome in
      CBT for patients with SP. The field is in need of conceptual and methodological
      improvements if more solid findings should be hoped for.

PMID- 20055731
TI  - The use of the vaginal ring and transdermal patch among adolescent girls in
      Finland.
AB  - OBJECTIVE: Little is known about the use of the vaginal ring and transdermal
      patch in representative adolescent populations although these contraceptives are
      supposed to be a good option for that age group. The aim of this study was to
      determine the use of the vaginal ring and that of the transdermal patch and to
      compare these with the use of oral contraceptives (OCs) and emergency
      contraception in adolescent girls residing in Finland. METHODS: As part of the
      Adolescent Health and Lifestyle Survey a questionnaire was mailed to a
      representative sample of girls aged 14, 16 or 18 years residing in Finland. Of
      these 3029 (72%) responded. RESULTS: The use of the vaginal ring (0.9%) and that
      of the transdermal patch (0.1%) were uncommon whereas OCs were commonly resorted
      to (20%). Only 0.6% of girls aged 16 and 2.5% of those aged 18 used the vaginal
      ring or the transdermal patch. Fifteen percent of girls had ever used emergency
      contraception. CONCLUSION: The vaginal ring and the transdermal patch are rarely
      used by adolescents. Our findings suggest that these novel contraceptive methods
      have not been adopted by family planning services.

PMID- 20055732
TI  - Form birefringence as applied to biopolymer and inorganic material
      supraorganization.
AB  - I review here form, or textural, birefringence (Delta(F)) in the context of
      advances in the field, as well as with regard to findings and applications in the
      physics of photonic devices, fibers maintaining polarization, photonic crystal
      fibers, and in biopolymers present in extracellular matrices and the myelin
      sheath. Some advantages of applying knowledge of Delta(F) to biological fields
      involving biopolymers, especially collagen fibers, are considered in more detail.
      Tendon and cartilage collagen fibers have been regarded as a model of dense,
      highly aggregated biopolymers with preferential orientations. Owing to their
      supramolecular organization, such materials may be used to study molecular order
      by using anisotropic optical properties, especially Delta(F). Differences between
      collagen type I- and collagen type II-rich structures, and similarities between
      collagen crimp and second harmonic generation images are reported. Based on data
      reported here, it is possible to deduce that collagen type I supramolecular
      organization has nonlinear optical properties and that tendon segments can
      conduct red laser light. With respect to nerve fibers, the detection and
      measurements of Delta(F) have allowed the myelin sheath to be considered a
      smectic liquid crystal.

PMID- 20055733
TI  - Practical histological methods for use with cultured cells.
AB  - The histology laboratory can face many challenges when small, often critical,
      specimens of cultured cells are submitted for specialized immunocytochemical
      studies or special stains. Although clinical pathology labs often receive cell
      preparations, these usually contain enough cells so that pellets can be formed by
      centrifugation, and the pellets directly embedded and sectioned. Research labs,
      however, often need to submit very small samples of cells for experimental
      studies. We summarize here a number of techniques that currently are available
      and methods we have developed and/or adapted and used in our laboratory over the
      years. We describe the utility of multi-chambered slides for cell culture and
      histologic studies, multi-well cell culture plates, monolayer cell culture on
      specialized coated cell wells, cell well inserts, and agarose embedding
      techniques for small cultures of cells and for cultures that require antigen
      retrieval or multiple antibody localizations. Traditional double embedding
      techniques, such as the use of agar, are also cited.

PMID- 20055734
TI  - Exogenous thymosin beta4 prevents apoptosis in human intervertebral annulus cells
      in vitro.
AB  - Loss of cells in the human disc due to programmed cell death (apoptosis) is a
      major factor in the aging and degenerating human intervertebral disc. Our
      objective here was to determine if thymosin beta(4) (TB4), a small,
      multifunctional 5 kDa protein with diverse activities, might block apoptosis in
      human annulus cells cultured in monolayer or three-dimensional (3D) culture.
      Apoptosis was induced in vitro using hydrogen peroxide or serum starvation.
      Annulus cells were processed for identification of apoptotic cells using the
      TUNEL method. The percentage of apoptotic cells was determined by cell counts.
      Annulus cells also were treated with TB4 for determination of proliferation, and
      proteoglycan production was assessed using cell titer and 1,2 dimethylmethylamine
      (DMB) assays and histological staining. A significant reduction in disc cell
      apoptosis occurred after TB4 treatment. The percentage of cells undergoing
      apoptosis decreased significantly in TB4 treated cells in both apoptosis
      induction designs. TB4 exposure did not alter proteoglycan production as assessed
      by either DMB measurement or histological staining. Our results indicate the need
      for further studies of the anti-apoptotic effect of TB4 and suggest that TB4 may
      have therapeutic application in future biological therapies for disc
      degeneration.

PMID- 20055736
TI  - Murine models of airway fungal exposure and allergic sensitization.
AB  - Inhalation of common indoor filamentous fungi has been associated with the
      induction or exacerbation of allergic respiratory disease. The understanding of
      fungal inhalation and allergic sensitization has significantly advanced with the
      use of small animal models, especially mouse models. Numerous studies have
      employed different animal exposure and sensitization techniques, each with
      inherent advantages and disadvantages that are addressed in this review. In
      addition, most studies involve exposure of animals to fungal spores or spore
      extracts while neglecting the influence of hyphal or subcellular fragment
      exposures. Recent literature examining the potential for hyphae and fungal
      fragments to induce or exacerbate allergy is discussed. Innate immune recognition
      of fungal elements and their contribution to lung allergic inflammation in animal
      models are also reviewed. Though physical properties of fungi play an important
      role following exposure, host immune development is also critical in airway
      inflammation and allergy. We discuss the importance of environmental factors that
      influence early immune development and subsequent susceptibility to allergy.
      Murine studies that examine the role of intestinal microflora and prenatal or
      early life environmental factors that promote allergic sensitization are also
      evaluated. Future studies will require animal models that accurately reflect
      natural fungal exposures and identify environmental factors that influence immune
      development and thus promote respiratory fungal allergy and disease.

PMID- 20055737
TI  - Development of murine models of disseminated infection by Neoscytalidium
      dimidiatum.
AB  - We have developed two murine models of disseminated infections by Neoscytalidium
      dimidiatum, an emerging dematiaceous fungus. Immunosuppressed mice were
      challenged through the lateral tail vein with 1 x 10(5) or 1 x 10(6) CFU/ml and
      immunocompetent animals with 1 x 10(6) or 1 x 10(7) CFU/ml. N. dimidiatum var.
      dimidiatum was more virulent than the nonpigmented variety, N. dimidiatum var.
      hyalinum. All mice infected with N. dimidiatum var. dimidiatum died within 8 days
      while those infected with N. dimidiatum var. hyalinum survived to the end of the
      experiment. Fungal load in tissue was also higher in animals inoculated with N.
      dimidiatum var. dimidiatum. In general, of the five organs tested, spleens and
      kidneys were most affected.

PMID- 20055738
TI  - A new species, Aspergillus persii, as an agent of onychomycosis.
AB  - Onychomycosis due to non-dermatophytic fungi is a well-known and increasingly
      common infection. For the first time ever, we report two cases of onychomycosis
      caused by Aspergillus persii, a recently described new Aspergillus species. After
      ten and three years respectively, both patients showed relapsing nail infections,
      and mycological tests were still positive for A. persii. In vitro antifungal
      susceptibility tests demonstrated that both strains were only susceptible to
      itraconazole, voriconazole, posaconazole and terbinafine of the agents tested.

PMID- 20055739
TI  - Role of glycogen synthase kinase 3 (GSK-3) in innate immune response of human
      immature dendritic cells to Aspergillus fumigatus.
AB  - Dysregulation of the Th1/Th2 cytokine balance and a switch to a Th2 immune
      response contribute to the development of and the unfavorable outcome from
      invasive aspergillosis (IA). We explore in this paper the role of glycogen
      synthase kinase 3 (GSK-3) in human immature dendritic cells (iDCs) relative to
      infection caused by A. fumigatus by the use of GSK-3 inhibitors (LiCl, SB415286)
      and RNA interference technology. In iDCs exposed to A. fumigatus germ tubes,
      inhibition of GSK-3 with LiCl or SB415286, as well as transfection with small
      interfering RNA, led to markedly elevated expression of the anti-inflammatory
      cytokine IL-10. In contrast, pro-inflammatory cytokine response was only
      partially regulated by GSK-3. Screening of patients after allogeneic stem cell
      transplantation (with or without IA) for the presence of genetic markers
      (rs334558, rs6438552) in the GSK-3 gene revealed no significant association with
      an increased risk for IA. In conclusion, GSK-3 might be involved in the
      regulation of the anti-inflammatory response of iDCs in the context of infections
      due to A. fumigatus, albeit the exact mechanisms have to be clarified in future
      experiments.

PMID- 20055740
TI  - Swimming pool deck as environmental reservoir of Fusarium.
AB  - While investigations on fungal contamination of swimming pools usually focus on
      dermatophytes, data on other potentially pathogenic molds are scarce. Here, we
      report the investigation of fungal colonization of the deck surrounding a
      hospital physical therapy swimming pool. Five series of samples from 8 sites were
      collected over one year from the pool surroundings. Concomitantly, 58 patients
      using the swimming pool were examined and samples obtained from those with
      suspected onychomycosis. All surface samples were positive for fungi, with
      Fusarium the most frequently recovered from 22 of 27 samples of sites surrounding
      the pool. Among the outpatients evaluated, two presented with a mixed
      onychomycosis from which Fusarium and Trichophyton rubrum were isolated. The
      questions of possible acquisition from the swimming pool area must be considered
      in both cases as the ungual lesions had developed within the previous three
      months. This warrants further studies to better understand the epidemiology of
      potentially pathogenic molds in areas surrounding pools in order to adopt
      appropriate measures to avoid contamination. This is of particular importance
      within medical institutions, considering the potential role of Fusarium
      onychomycosis as a starting point for disseminated infections in
      immunocompromised patients.

PMID- 20055741
TI  - Rhinocladiella aquaspersa, proven agent of verrucous skin infection and a novel
      type of chromoblastomycosis.
AB  - We report a case of chromoblastomycosis which resembled sporotrichosis due to the
      presence of warty nodules and lymphatic distribution on the forearm in a 56-year
      old male. Mycological and histopathological investigation of exudates and biopsy
      tissue samples revealed a granulomatous lesion with muriform cells, the hallmark
      of chromoblastomycosis. The infection showed only localized expansion with
      verrucous plaques suggesting a new clinical type of the disease. The causative
      agent was identified as Rhinocladiella aquaspersa. This case prompted a study of
      the clinical spectrum of R. aquaspersa, through which we identified a second case
      caused by this fungus in a 62-year-old Brazilian female. The case was unusual in
      that R. aquaspersa exhibited hyphae rather than muriform cells in tissue. Given
      the difficulties treating chromoblastomycosis and other infections caused by
      melanized fungi, we evaluated the in vitro activities of extended-spectrum
      triazoles, amphotericin B, and echinocandins against these clinical isolates of
      R. aquaspersa. Itraconazole (MIC; 0.063 mg/l) and posaconazole (MIC; 0.125 mg/l)
      had the highest in vitro activities, while voriconazole and isavuconazole had
      somewhat lower activities (MICs; 2 mg/l) against the isolates. Amphotericin B and
      anidulafungin each had an MIC of 1 mg/l, whereas the MIC of caspofungin was 8
      mg/l.

PMID- 20055743
TI  - The effects of antifungal agents to conidial and hyphal forms of Aspergillus
      fumigatus.
AB  - Susceptibility testing for Aspergillus fumigatus is usually performed using a
      fungal conidial suspension. However, assessment of the susceptibility of fungal
      hyphae may be more relevant in attempting to mimic the fungal status in infected
      tissues. In the present study of 12 A. fumigatus clinical isolates and 1 ATCC
      strain, the antifungal susceptibilities of conidial suspensions, suspensions of
      hyphal fragments and of hyphal clumps were determined by the XTT-based broth
      susceptibility assay measuring decrease in fungal metabolic activity.
      Amphotericin B inhibited A. fumigatus conidia and hyphal fragments in a sharp
      concentration-dependent manner, with inhibitory concentrations (ICs) of 1
      microg/ml for both fungal structures, whereas, hyphal clumps were inhibited at 8
      microg/ml. Conidia and hyphal fragments were inhibited by the azoles itraconazole
      and voriconazole in a more gradual concentration-dependent manner, with ICs of
      0.5 microg/ml for both structures with both agents. Hyphal clumps were not
      inhibited by the azoles at all. Caspofungin inhibited A. fumigatus in a moderate,
      neither sharp nor gradual, concentration-dependent manner. ICs for conidia were
      128 microg/ml and inhibition in metabolic activity was not obtained for both
      hyphal growth forms. Antifungal susceptibility of conidia was also determined
      using the E-test in which it was found that the XTT assaygave comparable ICs for
      amphotericin B, itraconazole and voriconazole but not for caspofungin.

PMID- 20055744
TI  - A dark strain in the Fusarium solani species complex isolated from primary
      subcutaneous sporotrichioid lesions associated with traumatic inoculation via a
      rose bush thorn.
AB  - Fusarium species are hyaline hyphomycetes widely distributed in nature and
      documented agents of both superficial and systemic infections in humans. In this
      paper, we report a darkly-pigmented and initially non-sporulating isolate in the
      Fusarium solani species complex (FSSC) causing a post-traumatic sporotrichoid
      infection in an otherwise healthy, male patient. Sequencing of multiple loci
      showed that the isolate represented an otherwise unknown lineage, possibly
      corresponding to a separate species, within the multi-species F. solani complex.
      In prolonged culture, the non-sporulating isolate produced revertant wild-type
      subcultures with typical Fusarium conidiation. This suggests that the original
      dense, dark, non-sporulating isolate was a host-adapted form selected in vivo for
      characters compatible with human pathogenicity. The production of such forms by
      Fusarium species is increasingly recognized now that sequencing has allowed the
      identification of highly atypical isolates. In vitro antifungal susceptibility of
      the isolate was investigated against seven conventional and two newly approved
      antifungal agents. The isolate showed in vitro resistance to amphotericin B, but
      appeared susceptible to itraconazole and terbinafine. A cure was ultimately
      achieved with combined terbinafine/itraconazole therapy with prolonged
      itraconazole follow-up therapy.

PMID- 20055745
TI  - Acquired resistance to voriconazole and itraconazole in a patient with pulmonary
      aspergilloma.
AB  - We describe the development of resistance in an Aspergillus fumigatus strain,
      originally sensitive to itraconazole and voriconazole, recovered from a case of
      pulmonary aspergilloma treated with voriconazole. A G448S mutation on the cyp51A
      gene was detected by sequencing. Frequent culture and in vitro antifungal
      susceptibility testing is suggested for early detection of the development of
      multi-azole resistance in patients on long-term therapy for A. fumigatus
      infections.

PMID- 20055746
TI  - Biofilm formation on intrauterine devices in patients with recurrent vulvovaginal
      candidiasis.
AB  - A biofilm is a complex community of surface-associated cells enclosed in a
      polymer matrix. They attach to solid surfaces and their formation can be affected
      by growth conditions and co-infection with other pathogens. The presence of
      biofilm may protect the microorganisms from host defenses, as well as
      significantly reduce their susceptibility to antifungal agents. Pathogenic
      microbes can form biofilms on the inert surfaces of implanted devices such as
      catheters, prosthetic cardiac valves and intrauterine devices (IUDs). The present
      study was carried out to analyze the presence of biofilm on the surface of
      intrauterine devices in patients with recurrent vulvovaginal candidiasis, and to
      determine the susceptibility profile of the isolated yeasts to amphotericin B and
      fluconazole. Candida albicans was recovered from the IUDs and it was found to be
      susceptible to the antifungal agents when tested under planktonic growing
      conditions. These findings indicate the presence of the biofilm on the surface of
      the IUD as an important risk factor for recurrent vulvovaginal candidiasis.

PMID- 20055747
TI  - New platform for controlled and sustained delivery of the EGF receptor tyrosine
      kinase inhibitor AG1478 using poly(lactic-co-glycolic acid) microspheres.
AB  - Inhibition of the epidermal growth factor receptor (EGFR) reduces tumour growth
      and metastases and promotes axon regeneration in the central nervous system.
      Current EGFR inhibition strategies include the administration of reversible small
      molecule tyrosine kinase inhibitors (TKIs). However, to be effective in vivo
      sustained delivery is required. This study explored the feasibility of
      encapsulating the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline
      (AG1478) in poly(lactic-co-glycolic acid) (PLGA) microspheres using three
      different emulsion methods: solid-in-oil-in-water, oil-in-water and oil-in-water
      with co-solvent. Addition of a co-solvent increased loading and release of AG1478
      and significantly (p < 0.001) decreased microsphere size. Co-solvent addition
      also prolonged AG1478 release from 6 months to over 9 months. Once released
      AG1478 remained bioactive and inhibited EGFR in immortalized rat fibroblasts and
      EGFR-amplified human carcinoma cells. These results demonstrate that AG1478 can
      be encapsulated in PLGA with sustained release and retain bioactivity; thereby
      providing a new platform for controlled administration of EGFR TKIs.

PMID- 20055748
TI  - Formulation, characterization and testing of tetracaine hydrochloride-loaded
      albumin-chitosan microparticles for ocular drug delivery.
AB  - Most ocular surgical procedures take approximately 60 min to complete, the
      anaesthetic property of the safest drug, tetracaine, is initiated in a few
      minutes and lasts approximately 10-15 min. The purpose of the present study was
      to develop an ocular tetracaine formulation which can produce an immediate onset
      of action and/or longer duration of action during the entire surgical procedure.
      Tetracaine-loaded microparticle formulation was prepared by the method of spray
      drying and characterized in terms of size, zeta potential, morphology, thermal
      stability and release pattern. The study reports a microparticulate ocular
      formulation with minimum cytotoxicity and optimum cellular uptake. In addition,
      microencapsulated tetracaine was found to significantly increase the duration of
      action of the drug up to 4-fold. Taken together, the results presented in this
      work described albumin-chitosan microparticles to be an effective delivery
      platform for ocular anaesthetic agents and a potential treatment of various
      ocular diseases.

PMID- 20055749
TI  - Targeted delivery of antigens to the gut-associated lymphoid tissues: 2. Ex vivo
      evaluation of lectin-labelled albumin microspheres for targeted delivery of
      antigens to the M-cells of the Peyer's patches.
AB  - The purpose of this study was to evaluate the possibility of lectin-coupled
      microspheres to improve the targeted delivery of protein antigens to the lymphoid
      tissues of mucosal surfaces. Bovine serum albumin containing acid phosphatase
      model protein and polystyrene microspheres were coupled with mouse M-cell
      specific Ulex europaeus lectin. The coupling efficiency, physical characteristics
      and the binding capabilities of the microspheres to the follicle associated
      epithelium of the Peyer's patches were evaluated in vitro and ex vivo in mice
      intestine. The results showed that coupling of lectin to albumin microspheres did
      not significantly affect the bioactivity of the encapsulated acid phosphatase
      model protein. It was also shown that there was preferential binding of the
      lectin-coupled microspheres to the follicle-associated epithelium. It was
      concluded from the results of the study that coupling of ligands such as lectin
      specific to cells of the follicle associated epithelium can increase the
      targeting of encapsulated candidate antigens for delivery to the Peyer's patches
      of the intestine for improved oral delivery.

PMID- 20055750
TI  - The importance of tissue penetration in achieving successful antimicrobial
      treatment of nosocomial pneumonia and complicated skin and soft-tissue infections
      caused by methicillin-resistant Staphylococcus aureus: vancomycin and linezolid.
AB  - BACKGROUND: The rising prevalence of nosocomial methicillin-resistant
      Staphylococcus aureus (MRSA) and the recent emergence of community-associated
      MRSA are major clinical, public health, and economic challenges. MRSA is a
      leading cause of nosocomial pneumonia and complicated skin and soft-tissue
      infections (cSSTI). Vancomycin and linezolid are two commonly used antimicrobial
      agents with activity against Gram-positive pathogens, particularly MRSA, that are
      used to treat both nosocomial pneumonia and cSSTI. Recently, the therapeutic
      efficacy of vancomycin in the treatment of hospitalized patients with MRSA
      infections has been questioned due to the emergence of MRSA strains with reduced
      susceptibility to vancomycin together with concerns related to inadequate dosing
      and poor tissue penetration of the drug. SCOPE: A literature review was conducted
      to investigate the pharmacokinetics and pulmonary and tissue penetration of
      vancomycin and linezolid. Using MEDLINE and EMBASE, the most relevant articles in
      English published over the past 25 years (up to October 2008) were identified and
      summarized. Studies in human volunteers and adult patients that measured
      concentrations of antibiotic in serum, epithelial lining fluid (ELF), and tissue
      were selected for further review. FINDINGS: For both drugs, pharmacokinetic
      studies were conducted in diverse patient populations and employed varying
      techniques to measure tissue concentrations. Vancomycin concentrations in ELF
      ranged from 5 to 25% of simultaneous plasma levels, while concentrations in whole
      homogenized lung tissue were slightly higher (24-41%). Distribution of vancomycin
      into soft tissue was variable. For linezolid, overall mean concentrations in ELF
      and in soft tissue were generally similar or higher than simultaneous plasma
      levels, although variability in tissue penetration across studies in healthy
      volunteers and patients was seen. LIMITATIONS: The studies included in this
      review vary greatly in their designs and patient populations; this, together with
      methodologic difficulties, limits the interpretation of the data. CONCLUSIONS: In
      the absence of clinical data correlating ELF concentrations and clinical outcome,
      the clinical significance of differences in pulmonary penetration of vancomycin
      and linezolid is unknown. Higher vancomycin serum concentrations may be necessary
      to achieve appropriate lung concentrations to optimize treatment outcomes.
      Linezolid demonstrates adequate penetration into lung and other soft issues with
      sustained concentrations above the minimum inhibitory concentrations for
      susceptible pathogens, including MRSA, for the majority of the dosing interval.
      Examination of the pharmacokinetic data adds insights not provided by the
      clinical trial data and together provides clinicians with a more comprehensive
      basis for selecting appropriate antimicrobial therapy for the treatment of
      serious MRSA infections.

PMID- 20055751
TI  - Risk reduction of non-vertebral fractures with intravenous ibandronate: post-hoc
      analysis from DIVA.
AB  - OBJECTIVE: In the BONE study (3 years' duration), daily oral ibandronate 2.5 mg
      reduced vertebral fracture risk by 62% (vs. placebo; p = 0.0001). In the DIVA
      study (2 years' duration), i.v. ibandronate 2 mg every 2 months (q2mo) or 3 mg
      every 3 months (q3mo) was superior to daily oral ibandronate in terms of BMD
      gains (p < 0.001) and normalisation of bone turnover markers, suggesting
      potential antifracture efficacy with the licensed i.v. regimen (3 mg q3mo). To
      evaluate this, a post-hoc analysis of non-vertebral fracture incidence was
      performed using DIVA study individual patient data. METHODS: Both i.v. doses had
      the same annual cumulative exposure (ACE) - 12 mg. Therefore, data for these two
      regimens were pooled. This higher dose was compared with 2.5 mg daily oral
      ibandronate (ACE 5.5 mg) to maintain trial randomisation. Osteoporotic non
      vertebral fractures were captured as a secondary endpoint. Time-to-event analysis
      was conducted using Kaplan-Meier methodology; hazard ratios (HRs) were derived
      from a Cox model with adjustments for clinical fracture, age and BMD. The DIVA
      trial was not primarily designed to assess fracture efficacy. RESULTS: The rate
      of non-vertebral fractures was significantly reduced when ibandronate ACE 12 mg
      (3 mg q3mo and 2 mg q2mo i.v.) was compared with ACE 5.5 mg (2.5 mg daily oral).
      The non-vertebral fracture incidence was 3.1% versus 4.8%, respectively,
      representing a 43% relative risk reduction with i.v. ibandronate (p = 0.0489;
      adjusted HR 0.569 [95% confidence interval: 0.324, 0.997]). Time to non-vertebral
      fracture was also extended for high- versus low-dose ibandronate (p = 0.048).
      CONCLUSIONS: A significant effect on non-vertebral fracture risk reduction was
      seen when high i.v. ibandronate doses were compared with a lower oral dose. This
      post-hoc analysis indicates greater antifracture efficacy for the licensed
      quarterly i.v. regimen versus daily oral dosing.

PMID- 20055752
TI  - Ion- and pH-activated novel in-situ gel system for sustained ocular drug
      delivery.
AB  - Poor bioavailability (<1%) of drugs from conventional eye drops is mainly due to
      the various precorneal loss factors which include rapid tear turnover, systemic
      drug absorption through naso-lachrymal duct, transient residence time of the drug
      solution in the cul-de-sac and the relative impermeability of the drugs to
      corneal epithelial membrane. The present study describes the formulation and
      evaluation of chitosan and gellan gum based novel in-situ gel system activated by
      dual physiological mechanisms. Chitosan (a pH-sensitive polymer) in combination
      with gellan gum (an ion-activated polymer) were used as gelling agent. Timolol
      maleate, the drug which is frequently used for glaucoma therapy was used as model
      drug to check the efficacy of the formulation. The developed formulation was
      characterized for various in vitro parameters, for example, clarity, gelation pH,
      isotonicity, sterility, viscosity, transcorneal permeation profile, and ocular
      irritation. Ocular retention was studied by gamma scintigraphy and a significant
      increase in retention time was observed. The formulation was also found to be
      nonirritant and well tolerable. The developed system can be a viable alternative
      to conventional eye drops for the treatment of various ocular diseases and is
      suitable for clinical application.

PMID- 20055753
TI  - Regulatory effects of nitric oxide on Src kinase, FAK, p130Cas, and receptor
      protein tyrosine phosphatase alpha (PTP-alpha): a role for the cellular redox
      environment.
AB  - The role of NO in regulating the focal adhesion proteins, Src, FAK, p130 Cas, and
      PTP-alpha, was investigated. Fibroblasts expressing PTP-alpha (PTP-alpha(WT)
      cells), fibroblasts "knockout" for PTP-alpha (PTP-alpha(-/-) cells), and
      "rescued" "knockout" fibroblasts (PTP-alpha A5/3 cells) were stimulated with
      either S-nitroso-N-acetylpenicillamine (SNAP) or fetal bovine serum (FBS). FBS
      increased inducible NO synthase in both cell lines. Activation of Src mediated
      either by SNAP or by FBS occurred independent of dephosphorylation of Tyr527 in
      PTP-alpha(-/-) cells. Both stimuli promoted dephosphorylation of Tyr527 and
      activation of Src kinase in PTP-alpha(WT) cells. NO-mediated activation of Src
      kinase affected the activities of FAK and p130Cas and was dependent on the
      expression of PTP-alpha. Analogous to tyrosine phosphorylation, SNAP and FBS
      stimulated differential generation of NO and S-nitrosylation of Src kinase in
      both cell lines. Incubation with SNAP resulted in higher levels of NO and S
      nitrosylation of immunoprecipitated Src in PTP-alpha(-/-) cells (oxidizing redox
      environment) as compared with the levels of NO and S-nitrosylated Src in PTP
      alpha(WT) cells (reducing redox environment). SNAP differentially stimulated cell
      proliferation of both cell lines is dependent on the intracellular redox
      environment, Src activity, and PTP-alpha expression. This dependence also is
      observed with FBS-stimulated cell migration.

PMID- 20055754
TI  - Enhanced hepatic Nrf2 activation after ursodeoxycholic acid treatment in patients
      with primary biliary cirrhosis.
AB  - The cytoprotective mechanisms of ursodeoxycholic acid (UDCA) in primary biliary
      cirrhosis (PBC) have not been fully clarified. UDCA has some antioxidant
      properties. Nuclear factor-E2-related factor-2 (Nrf2) plays a critical role in
      protecting a variety of tissues against oxidative stress. Therefore, to
      investigate the potential antioxidant effects of UDCA in PBC, we determined the
      intracellular status of both oxidant stress and antioxidant defenses in paired
      pre- and posttreatment liver biopsies from 13 PBC patients by immunodetection of
      8-hydroxydeoxyguanosine (8-OHdG), Nrf2-, and Nrf2-mediated antioxidant proteins.
      After UDCA treatment, the number of 8-OHdG-positive hepatocytes or bile duct
      cells decreased with improvement of hepatic injury. The hepatic levels of both
      total and phosphorylated Nrf2 protein were increased, along with upregulation of
      nuclear phosphorylated Nrf2 expression in bile duct cells. In addition, the
      levels of both thioredoxin (TRX) and thioredoxin reductase 1 (TrxR1) protein were
      increased in the liver after UDCA. The upregulation of hepatic TRX or TrxR1
      protein expression positively correlated with that of total Nrf2 protein
      expression. In conclusion, UDCA treatment can enhance hepatic Nrf2 activation and
      upregulate hepatic TRX and TrxR1 protein expression. Hepatic Nrf2 activation may
      play a role in the therapeutic response to UDCA in PBC.

PMID- 20055755
TI  - Characterization of non-cytosolic hexokinase activity in white skeletal muscle
      from goldfish (Carassius auratus L.) and the effect of cold acclimation.
AB  - HK (hexokinase) is an enzyme involved in the first step in the glucose metabolism
      pathway, converting glucose into G6P (glucose 6-phosphate). Owing to the
      importance of skeletal muscle for fish swimming and acclimation processes, we
      used goldfish (Carassius auratus L.) white muscle in order to investigate
      subcellular distribution and kinetics of HK. In this study, we report that HK
      activity is predominantly localized in the mitochondrial fraction [NC-HK (non
      cytosolic HK)] in goldfish white muscle. Studies of the kinetic parameters
      revealed that the Km (Michaelis-Menten constant) for glucose was 0.41+/-0.03 mM
      and that for mannose was 3-fold lower, whereas the affinity for fructose was too
      low to be measured. The Km for ATP was 0.88+/-0.05 mM, whereas no activity was
      observed when either GTP or ITP was used as a phosphate donor. A moderate
      inhibition (20-40%) was found for ADP and AMP. Similar to mammalian HK, G6P and
      glucose analogues were able to promote an inhibition of between 85 and 100% of
      activity. Here, we found that acclimation of goldfish at 5 degrees C promoted a
      2.5-fold increase in NC-HK compared with its counterpart acclimated at 25 degrees
      C. However, cytosolic HK activity was not altered after thermal acclimation. In
      summary, our results suggest that the goldfish has a constitutive NC-HK that
      shows some similarities to mammalian HK-II and, curiously, may play a role in the
      broad metabolic changes required during the cold acclimation process.

PMID- 20055756
TI  - Properties and antityrosinase activity of sericin from various extraction
      methods.
AB  - The present study investigated the chemical properties and antityrosinase
      activities of SS (silk sericin) extracted from different Thai silk strains via
      various extraction methods. Different silk strains contain distinct SS with
      various amino acid compositions, which are significantly influenced by the
      extraction method used. Urea extraction of SS was the only method that provided
      clearly distinguishable bands and had the most significant impact on SS
      conformation as illustrated by FTIR (Fourier-transform infrared) spectra. The use
      of urea or either acidic or alkaline chemicals in the extraction process also
      influenced SS thermal behaviour. With regard to biological activity, SS extracted
      using urea exhibited the highest antityrosinase activity, whereas alkali-degraded
      SS showed no inhibition of mushroom tyrosinase. Pigments, primarily flavonoids
      and carotenoids from silk cocoons, were also found to enhance tyrosinase
      inhibition of SS.

PMID- 20055757
TI  - Shear stress activates Akt during vascular smooth muscle cell reorientation.
AB  - Vascular intervention procedures can lead to endothelial damage and expose the
      underlying VSMCs (vascular smooth muscle cells) to shear stress. Although shear
      stress has been implicated in the proliferation and migration of VSMCs, the
      molecular mechanism(s) underlying these events are not well understood. In the
      present study, we examined the effect of shear stress on VSMC reorientation and
      the activation of Akt (also called protein kinase B) pathway signalling. Cells
      were subjected to a shear of 9.8 dynes/cm2 (1 dyne=10-5 N) for 0 min, 5 min, 15
      min, 30 min, 1 h, 4 h and 24 h. Shear stress caused the VSMCs to realign at an
      angle that was approximately 45 degrees relative to the shear force vector after
      24 h. Immunoblotting demonstrated that the phosphorylations of Akt and Akt
      related signalling proteins [mTOR (mammalian target of rapamycin), PTEN
      (phosphatase and tensin homologue deleted on chromosome 10) and p70S6k (p70 S6
      kinase)] were increased after shear stimulation. These results indicate that the
      activation of the Akt pathway signalling is closely correlated with shear-induced
      VSMC reorientation.

PMID- 20055758
TI  - Whole mitochondrial genome screening in two families with hearing loss: detection
      of a novel mutation in the 12S rRNA gene.
AB  - Sensorineural hearing loss has been described in association with different
      mitochondrial multisystemic syndromes, often characterized by an important
      neuromuscular involvement. Until now, mutations in mitochondrial DNA, especially
      in the 12S rRNA, the tRNASer(UCN) and the tRNALeu(UUR) genes, were implicated in
      syndromic or non-syndromic hearing loss either as a primary cause or as
      predisposing factors. In the present study, we performed a whole mitochondrial
      genome screening in two unrelated Tunisian families with inherited hearing loss.
      Results showed the presence of a novel mutation in the mitochondrial 12S rRNA
      gene in the two probands of these two families who belong to two different
      haplogroups: L3 and H6a1. The m.735A>G mutation affects a conserved nucleotide of
      the mitochondrial 12S rRNA gene in primates and other species and had a
      conservation index of 78.5% (11/14). We also detected known polymorphisms and sic
      novel mitochondrial variants. The present study confirmed that the mitochondrial
      12S rRNA gene is a hot spot for mutations associated with hearing impairment.

PMID- 20055759
TI  - Direct shoot regeneration from intact leaves of Arnebia euchroma (Royle) Johnston
      using thidiazuron.
AB  - The present study highlights the importance of preculture time and concentration
      of TDZ (thidiazuron) for direct regeneration from in vitro leaves (attached to
      shoots) in Arnebia euchroma. Shoot buds proliferated to form multiple shoots on
      MS medium (Murashige and Skoog medium) with 5.0 microM Kn. Different additives
      viz. ascorbic acid, PVP (polyvinylpyrrolidone), PVPP (polyvinylpolypyrrolidone)
      or activated charcoal (50, 100 and 250 mg/l each) were used to check the phenolic
      exudations. Direct shoot regeneration was obtained when shoots were initially
      precultured for 40 days on medium with a higher concentration of TDZ (20.0 muM)
      and then transferred to a lower concentration (5.0 microM TDZ). The identity of
      shoot buds was confirmed by histological studies. Regenerated shoots were
      cultured for 30 days on medium containing Kn (5.0 microM) for proliferation and
      then transferred to IBA (0.25 microM)-containing medium for rooting. Rooted
      plantlets were transferred to greenhouse with 45-50% survival.

PMID- 20055760
TI  - The CLIC5 (chloride intracellular channel 5) involved in C2C12 myoblasts
      proliferation and differentiation.
AB  - CLIC5 (chloride intracellular channel 5) is a CLIC (chloride intracellular
      channel) with various functions. Its high expression in skeletal muscle and
      association with actin-based cytoskeleton suggests that it may play an important
      role in muscle tissue. This study was conducted to examine whether CLIC5
      regulates the proliferation and differentiation of C2C12 myoblasts into myotubes.
      Differentiation of C2C12 myoblasts induced by switching to a differentiation
      culture medium was accompanied by a significant increase of CLIC5 protein
      expression level. Constitutive overexpression of CLIC5 was associated with
      reduced cell proliferation and more cells from G2/M phase into G0/G1 phase,
      followed by increased number and size of myotubes and up-regulation of muscle
      specific proteins of myosin heavy chain, myogenin and desmin. These results
      demonstrate that CLIC5 is involved in C2C12 proliferation and myogenic
      differentiation in vitro.

PMID- 20055761
TI  - Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor
      inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing
      agents.
AB  - The HIF (hypoxia-inducible factor) hydroxylases [PHDs or EGLNs (prolyl
      hydroxylases), which in humans are PHD isoforms 1-3, and FIH (factor inhibiting
      HIF)] regulate HIF levels and activity. These enzymes are Fe(II)/2-oxoglutarate
      dependent oxygenases, many of which are stimulated by ascorbate. We have
      investigated the ascorbate dependence of PHD2-catalysed hydroxylation of two
      prolyl hydroxylation sites in human HIF-1alpha, and of FIH-catalysed
      hydroxylation of asparaginyl hydroxylation sites in HIF-1alpha and in a consensus
      ankyrin repeat domain peptide. The initial rate and extent of hydroxylation was
      increased in the presence of ascorbate for each of these reactions. When
      ascorbate was replaced with structural analogues, the results revealed that the
      ascorbate side chain was not important in its contribution to HIF hydroxylase
      catalysis, whereas modifications to the ene-diol portion of the molecule negated
      the ability to promote hydroxylation. We investigated whether alternative
      reducing agents (glutathione and dithiothreitol) could be used to promote HIF
      hydroxylase activity, and found partial stimulation of hydroxylation in an
      apparently enzyme- and substrate-specific manner. The results raise the
      possibility of developing reducing agents targeted to specific HIF hydroxylase
      catalysed reactions.

PMID- 20055762
TI  - Procedural pain of an ultrasound-guided brachial plexus block: a comparison of
      axillary and infraclavicular approaches.
AB  - BACKGROUND: Ultrasound (US)-guided infraclavicular (IC) and axillary (AX) blocks
      have similar effectiveness. Therefore, limiting procedural pain may help to
      choose a standard approach. The primary aims of this randomized study were to
      assess patient's pain during the block and to recognize its cause. METHODS:
      Eighty patients were randomly allocated to the IC or the AX group. A blinded
      investigator asked the patients to quantify block pain on a Visual Analogue Scale
      (VAS 0-100) and to indicate the most unpleasant component (needle passes,
      paraesthesie or local anaesthetics injection). Sensory block was assessed every
      10 min. After 30 min, the unblocked nerves were supplemented. Patients were ready
      for surgery when they had analgesia or anaesthesia of the five nerves distal to
      the elbow. Preliminary scan time, block performance and latency times, readiness
      for surgery, adverse events and patient's acceptance were recorded. RESULTS: The
      axillary approach resulted in lower maximum VAS scores (median 12) than the
      infraclavicular approach (median 21). This difference was not statistically
      significant (P=0.07). Numbers of patients indicating the most painful component
      were similar in both groups. Patients in either group were ready for surgery
      after 25 min. Two patients in the IC group and seven in the AX group needed block
      supplementation (n.s.). Block performance times and number of needle passes were
      significantly lower in the IC group. Patients' acceptance was 98% in both groups.
      CONCLUSIONS: We did not find significant differences between the two approaches
      in procedural pain and patient's acceptance. The choice of approach may depend on
      the anaesthesiologist's experience and the patient's preferences.

PMID- 20055763
TI  - Analgesic efficacy of subcutaneous local anaesthetic wound infiltration in
      bilateral knee arthroplasty: a randomised, placebo-controlled, double-blind
      trial.
AB  - BACKGROUND: High-volume wound local infiltration analgesia is effective in knee
      arthroplasty, but the analgesic efficacy of subcutaneous wound infiltration has
      not been evaluated. METHODS: In a randomised, double-blind, placebo-controlled
      trial in 16 patients undergoing bilateral knee arthroplasty with high-volume
      local infiltration analgesia in the deeper layers, saline or ropivacaine 2 mg/ml
      was infiltrated into the subcutaneous part of the wound in each knee along with
      the placement of multi-fenestrated catheters in the subcutaneous wound layers in
      both knees. Pain was assessed for 6 h post-operatively and for 3 h after a bolus
      injection given through the catheter 24 h post-operatively. RESULTS: Visual
      analogue scale (VAS) pain scores were significantly lower from the knee
      infiltrated with ropivacaine compared with the knee infiltrated with saline in
      the subcutaneous layer of the wound, at rest (P<0.02), with flexion of the knee
      (P<0.04) and when the leg was straight and elevated (P<0.04). Twenty-four hours
      post-operatively, a decline in the VAS pain scores was observed in both groups,
      with no statistically significant difference between injection of ropivacaine or
      saline in the subcutaneously placed catheters (P>0.05). CONCLUSION: As part of a
      total wound infiltration analgesia intraoperative subcutaneous infiltration with
      ropivacaine in bilateral total knee arthroplasty is effective in early post
      operative pain management, while a post-operative subcutaneous bolus
      administration through a multiholed catheter 24 h post-operatively did not show
      improved analgesia compared with the administration of saline.

PMID- 20055764
TI  - Exposure to anaesthetic trace gases during general anaesthesia: CobraPLA vs. LMA
      classic.
AB  - BACKGROUND: To prospectively investigate the performance, sealing capacity and
      operating room (OR) staff exposure to waste anaesthetic gases during the use of
      the Cobra perilaryngeal airway (CobraPLA) compared with the laryngeal mask airway
      classic (LMA). METHODS: Sixty patients were randomly assigned to the CobraPLA or
      the LMA group. Insertion time, number of insertion attempts and airway leak
      pressures were assessed after induction of anaesthesia. Occupational exposure to
      nitrous oxide (N(2)O) and Sevoflurane (SEV) was measured at the anaesthetists'
      breathing zone and the patients' mouth using a photoacoustic infrared
      spectrometer. RESULTS: N(2)O waste gas concentrations differed significantly in
      the anaesthetist's breathing zone (11.7+/-7.2 p.p.m. in CobraPLA vs. 4.1+/-4.3
      p.p.m. in LMA, P=0.03), whereas no difference could be shown in SEV
      concentrations. Correct CobraPLA positioning was possible in 28 out of 30
      patients (more than one attempt necessary in five patients). Correct positioning
      of the LMA classic was possible in all 30 patients (more than one attempt in
      three patients). Peak airway pressure was higher in the CobraPLA group (16+/-3
      vs. 14+/-2 cmH(2)O, P=0.01). The average leak pressure of the CobraPLA was 24+/-4
      cmH(2)O, compared with 20+/-4 cmH(2)O of the LMA classic (P<0.001; all values
      means+/-SD). CONCLUSION: Despite higher airway seal pressures, the CobraPLA
      caused higher intraoperative N(2)O trace concentrations in the anaesthetists'
      breathing zone.

PMID- 20055765
TI  - Suspected allergy to local anaesthetics: follow-up in 135 cases.
AB  - BACKGROUND: Local anaesthetics (LA) are generally considered safe with respect to
      allergy. However, various clinical reactions steadily occur. Even though most
      reactions are manifestations of reflexes to perceptive stimuli, uncertainty often
      remains regarding a possible allergic mechanism. This uncertainty later leads to
      an avoidance of local anaesthesia and unnecessarily painful interventions,
      resource-consuming general anaesthesia or even the risk of re-exposure to other
      yet unidentified allergens. In the present study, follow-up procedures at an
      allergy clinic were analysed to examine the frequency of identified causative
      agents and pathogenetic mechanisms and evaluate the strength of the diagnostic
      conclusions. METHOD: The medical records of 135 cases with alleged allergic
      reactions to LA were reviewed. Diagnoses were based on case histories, skin
      tests, subcutaneous challenge tests and in vitro IgE analyses. RESULTS: Two
      events (1.5%) were diagnosed as hypersensitivity to LA, articaine-adrenaline and
      tetracaine-adrenaline, respectively. Ten reactions (7%) were diagnosed as IgE
      mediated allergy to other substances including chlorhexidine, latex,
      triamcinolone and possibly hexaminolevulinate. As challenge testing was not
      consistently performed with the culprit LA compound, follow-ups were short of
      definitely refuting hypersensitivity in 61% of the cases. The reported clinical
      manifestations were in general diagnostically unspecific, but itch and
      generalised urticaria were most frequent in test-positive cases. CONCLUSION:
      Reactions during local anaesthesia are rarely found to be an IgE-mediated LA
      allergy. Whenever the clinical picture is compatible with allergy, other
      allergens should also be tested.

PMID- 20055766
TI  - Hepatic effects of an open lung strategy and cardiac output restoration in an
      experimental lung injury.
AB  - BACKGROUND: Ventilation with high positive end-expiratory pressure (PEEP) can
      lead to liver dysfunction. We hypothesized that an open lung concept (OLC) using
      high PEEP impairs liver function and integrity dependent on the stabilization of
      cardiac output. METHODS: Juvenile female Pietrain pigs instrumented with flow
      probes around the common hepatic artery and portal vein, pulmonary and hepatic
      vein catheters underwent a lavage-induced lung injury. Ventilation was continued
      with a conventional approach (CON) using pre-defined combinations of PEEP and
      inspiratory oxygen fraction or with an OLC using PEEP set above the lower
      inflection point of the lung. Volume replacement with colloids was guided to
      maintain cardiac output in the CON(V+) and OLC(V+) groups or acceptable blood
      pressure and heart rate in the OLC(V-) group. Indocyanine green plasma
      disappearance rate (ICG-PDR), blood gases, liver-specific serum enzymes,
      bilirubin, hyaluronic acid and lactate were tested. Finally, liver tissue was
      examined for neutrophil accumulation, TUNEL staining, caspase-3 activity and heat
      shock protein 70 mRNA expression. RESULTS: Hepatic venous oxygen saturation was
      reduced to 18 + or - 16% in the OLC(V-) group, while portal venous blood flow
      decreased by 45%. ICG-PDR was not reduced and serum enzymes, bilirubin and
      lactate were not elevated. Liver cell apoptosis was negligible. Liver sinusoids
      in the OLC(V+) and OLC(V-) groups showed about two- and fourfold more
      granulocytes than the CON(V+) group. Heat shock protein 70 tended to be higher in
      the OLC(V-) group. CONCLUSIONS: Open lung ventilation elicited neutrophil
      infiltration, but no liver dysfunction even without the stabilization of cardiac
      output.

PMID- 20055767
TI  - Tuberculous meningitis.
AB  - Tuberculous meningitis is a severe form of extrapulmonary tuberculosis. The exact
      incidence and prevalence are not known. In countries with high burden of
      pulmonary tuberculosis, the incidence is expected to be proportionately high.
      Children are much more vulnerable. Human immunodeficiency virus-infected patients
      have a high incidence of tuberculous meningitis. The hallmark pathological
      processes are meningeal inflammation, basal exudates, vasculitis and
      hydrocephalus. Headache, vomiting, meningeal signs, focal deficits, vision loss,
      cranial nerve palsies and raised intracranial pressure are dominant clinical
      features. Diagnosis is based on the characteristic clinical picture, neuroimaging
      abnormalities and cerebrospinal fluid changes (increased protein, low glucose and
      mononuclear cell pleocytosis). Cerebrospinal fluid smear examination,
      mycobacterial culture or polymerase chain reaction is mandatory for
      bacteriological confirmation. The mortality and morbidity of tuberculous
      meningitis are exceptionally high. Prompt diagnosis and early treatment are
      crucial. Decision to start antituberculous treatment is often empirical. WHO
      guidelines recommend a 6 months course of antituberculous treatment; however,
      other guidelines recommend a prolonged treatment extended to 9 or 12 months.
      Corticosteroids reduce the number of deaths. Resistance to antituberculous drugs
      is associated with a high mortality. Patients with hydrocephalus may need
      ventriculo-peritoneal shunting. Bacillus Calmette-Guerin vaccination protects to
      some degree against tuberculous meningitis in children.

PMID- 20055768
TI  - Dysphagia and dysphonia among persons with post-polio syndrome - a challenge in
      neurorehabilitation.
AB  - OBJECTIVE: To study the occurrence of dysphagia and dysphonia in persons with
      post-polio syndrome admitted into the centre for neurological rehabilitation in
      Finland. MATERIALS AND METHODS: Fifty-one persons with post-polio syndrome who
      were rehabilitated at Kapyla Rehabilitation Centre, Helsinki, Finland, in 2003
      2004 were interviewed on problems with swallowing and voice production. Pulmonary
      function testing and grip strength measurement were performed. A clinical
      assessment of oral motor and laryngeal functions was carried out for those who
      reported daily problems with voice production or swallowing. RESULTS: Fifteen
      persons (29.4%) reported daily problems with swallowing or voice production. In
      the clinical assessment, the most commonly observed deficits in swallowing
      included decreased pharyngeal transit (n = 13) and the food catching in the
      throat (n = 4). The disturbance of co-ordination of breathing and voice
      production was seen in 12 persons. There were no significant differences in any
      of the potential predictors between the groups. CONCLUSIONS: Professionals need
      to be aware of the routine evaluation of dysphagia and dysphonia in patients with
      post-polio syndrome.

PMID- 20055769
TI  - Cognitive Impairment Questionnaire (CIMP-QUEST): reported topographic symptoms in
      MCI and dementia.
AB  - OBJECTIVE: The Cognitive Impairment Questionnaire (CIMP-QUEST) is an instrument
      based on information obtained by key informants to identify symptoms of dementia
      and dementia-like disorders. The questionnaire consists of three subscales
      reflecting impairment in parietal-temporal (PT), frontal (F) and subcortical (SC)
      brain regions. The questionnaire includes a memory scale and lists non-cognitive
      symptoms. The reliability and validity of the questionnaire were examined in 131
      patients with mild cognitive impairment (MCI) or mild dementia at a university
      based memory unit. METHODS/RESULTS: Cronbach alpha for all subscales was
      calculated at r = 0.90. Factor analysis supported the tri-dimensionality of CIMP
      QUEST's brain region-oriented construct. Test-retest reliability for a subgroup
      of cognitively stable MCI-patients (n = 25) was found to be r = 0.83 (P =
      0.0005). The correlation between the score on the cognitive subscales (PT + F +
      M) and Informant Questionnaire on Cognitive Decline in the Elderly was r = 0.83
      (P = 0.0005, n = 123). The memory subscale correlated significantly with episodic
      memory tests, the PT subscale with visuospatial and language-oriented tests, and
      the SC and F subscales with tests of attention, psychomotor tempo and executive
      function. CONCLUSIONS: CIMP-QUEST has high reliability and validity, and provides
      information about cognitive impairment and brain region-oriented symptomatology
      in patients with MCI and mild dementia.

PMID- 20055770
TI  - Valproate in children with newly diagnosed idiopathic generalized epilepsy.
AB  - OBJECTIVES: Sparse information on dose-response characteristics for initial
      antiepileptic drug monotherapy in children with idiopathic generalized epilepsy
      (IGE) is available. The aim of this study is to characterize the therapeutic dose
      of valproate in children with newly diagnosed IGE. MATERIALS AND METHODS: Effect
      of initial valproate monotherapy and doses associated with seizure freedom were
      examined in consecutive children with IGE identified from a New Onset Seizure
      Clinic. RESULTS: Of 84 patients identified, 48 (57%) became seizure-free on
      valproate monotherapy and another 10 patients became seizure-free but
      discontinued VPA because of adverse effects. The mean dose in seizure-free
      children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25
      mg/kg/day. CONCLUSIONS: Half of children became seizure-free on valproate
      monotherapy and did so at modest doses.

PMID- 20055771
TI  - Non-adherence to interferon-beta therapy in Swedish patients with multiple
      sclerosis.
AB  - OBJECTIVES: To explore the occurrence and reasons for stopping, switching or
      continuing first prescribed interferon-beta therapy in patients with multiple
      sclerosis in Sweden, with respect to demographic, clinical and/or therapy-related
      factors. MATERIALS AND METHODS: A retrospective study reviewing the medical
      charts of 259 patients with multiple sclerosis, comparing patients continuing
      therapy for at least 3 years with those switching or stopping therapy. RESULTS:
      Sixty 9% stopped (15%), or switched (54%), interferon-beta therapy within 3
      years. Stoppers had longer disease duration before starting therapy (P = 0.002),
      less frequently relapsing-remitting multiple sclerosis (P = 0.046), and more
      often Expanded Disability Status Scale scores 6-9.5 (P = 0.045) compared to
      Switchers. The most common reasons for switching/stopping therapy were perceived
      lack of effect and side-effects. CONCLUSIONS: Adherence to initial immune
      modulating therapy is low; identification of patients at higher risk of stopping
      therapy and provision of adequate support are essential.

PMID- 20055772
TI  - Serum somatostatin in early-stage Parkinson's disease.
AB  - OBJECTIVE: To compare levels of plasma digestive hormones in patients with and
      without nausea or vomiting during initial treatment of early-stage Parkinson's
      disease (PD). METHODS: This was a 3-week, open-label, randomized study of
      treatment with an antiparkinson drug in untreated PD patients. We measured the
      levels of plasma digestive hormones before (baseline) and 3 weeks after
      administration of an antiparkinson drug. RESULTS: Mean value of serum
      somatostatin at baseline was significantly increased in PD patients compared with
      the control group (P < 0.01). Serum somatostatin levels were significantly
      increased after treatment in subjects who experienced nausea or vomiting (P <
      0.01). However, significant increase in serum somatostatin levels after treatment
      was not observed in PD patients without nausea or vomitting. CONCLUSION: Serum
      somatostatin in early-stage PD patients before treatment was increased compared
      with healthy subjects. The nausea and vomiting induced by antiparkinson drugs may
      be related to uncontrolled somatostatin secretion through central vagus nerve
      dysfunction.

PMID- 20055773
TI  - Late subsequent ocular morbidity in retinopathy of prematurity patients, with
      emphasis on visual loss caused by insidious 'involutive' pathology: an
      observational series.
AB  - PURPOSE: This paper discusses late complications in eyes of surviving premature
      infants typically occurring years into the steady state attained after the
      initial ophthalmic events associated with preterm birth. The study focuses on
      insidious visual loss, as well as eventual vitreoretinal and anterior segment
      disorders. METHODS: We carried out a retrospective uncontrolled study of a case
      series (n = 31) of late complications to early ocular changes associated with
      very preterm delivery. The birth years of our subjects extended back to 1941, but
      only 15 more recent cases fulfilled contemporary criteria for a diagnosis of
      retinopathy of prematurity (ROP). RESULTS: Fourteen cases involved vitreoretinal
      pathology (median observation time 14 years, range 6-46 years) with late
      detachment and/or vitreous haemorrhage. Twelve cases primarily involved anterior
      segment pathology (median observation time 37 years, range 7-58 years). Eyes in
      the latter category often showed features of early arrested growth and anterior
      traction, which, in four eyes, eventually led to enucleation or exenteration as a
      result of a blind and painful terminal state. The last five cases (observation
      periods 22-38 years) were labelled 'miscellaneous'. Among the 31 patients, we
      identified a subgroup in which insidious visual loss was a common feature (n =
      20). Initially, some of these cases showed evidence of cicatricial ROP and low
      vision from early in life. Others retained useful vision and did not present
      obvious ocular incidents related to the actual visual acuity decline.
      CONCLUSIONS: Based on a variety of clinical ophthalmic preterm appearances, we
      propose the hypothesis that, in addition to increased structural vulnerability, a
      reduced functional reserve may pave the way for further abiotrophy or involution
      over time. This may manifest as reduced resistance to later ophthalmic events,
      such as disease or trauma, or simply the impact of age.

PMID- 20055774
TI  - Approach to seizures in the neonatal period: a European perspective.
AB  - In the neonatal period, seizures rank among the most common neurological
      symptoms, often indicating an underlying serious neurological condition. It is
      remarkable that although new tools have been incorporated into the diagnosis of
      neonatal seizures, there is no consensus about the therapeutic approach among
      different doctors and institutions. Hence, although phenobarbital is still
      considered the initial drug of choice, the protocols reported in the literature
      show a great variability in the approach to treatment of refractory seizures. We
      used a questionnaire to gain information regarding the treatment of seizures in
      the neonatal period in different European institutions. CONCLUSION: We conclude
      that phenobarbital is still the initial drug of choice followed by
      benzodiazepines, except in preterm infants with a birth weight below 1800 g. In
      refractory seizures, the use of continuous lidocaine infusion is most common. Of
      note, clinical studies with newer drugs have been mostly performed in the United
      States but not in Europe.

PMID- 20055775
TI  - Outcome of very preterm infants with Mycoplasma/Ureaplasma airway colonization
      treated with josamycine.

PMID- 20055776
TI  - Bullous lesions in Henoch Schonlein Purpura as indication to start systemic
      prednisone.
AB  - Henoch Schonlein Purpura (HSP) is usually mild and self-limiting, but it may be
      accompanied by severe complications such as bullous lesions. We describe the use
      of systemic prednisone in two patients with bullous lesions in HSP. The first
      patient presented with progressive bullous lesions distributed on the limbs that
      evolved into painful ulcers and necrosis. These were further complicated by a
      secondary skin infection. He then received 1 mg/kg/day prednisone after 9 days.
      Patient 2, a 10-year-old boy, presented with HSP and bullous lesions and received
      intravenous prednisone 1 mg/kg/day within 48 h after appearance of the bullous
      lesions. He recovered rapidly without any complications. CONCLUSION: To reduce
      the severity of HSP related bullous lesions and their sequelae, we would propose
      starting prednisone (1 mg/kg/day) as soon as the bullae appear. In addition to
      prednisone, analgesics and specialist skin care for bullae should be started.

PMID- 20055777
TI  - Predicting neurodevelopmental impairment in preterm infants by standardized
      neurological assessments at 6 and 12 months corrected age.
AB  - AIM: Neurodevelopmental impairment in very preterm infants can be reasonably
      diagnosed by 18-24 months corrected age, whereas the predictive value of earlier
      assessments is debated. We hypothesized that neurological findings at 6 and 12
      months indicative of subsequent cerebral palsy predict 18-24 months'
      neurodevelopmental impairment. METHODS: Neurodevelopmental examinations
      (Griffiths scales) at 20 months of age in 561 preterm infants (birth weight <1
      500 g) were compared with results of standardized neurological examinations
      (Early Motor Pattern Profile; EMPP) and Griffiths scales at 6 (n = 451) and 12
      months (n = 496) corrected age. RESULTS: Griffiths developmental quotients at 20
      months were weakly but significantly related to EMPP scores at 6 (R(s) = 0.328)
      and 12 months (R(s) = 0.493). Areas under receiver operator characteristic curves
      for the EMPP to predict neurodevelopmental impairment (Griffiths scores <or=75)
      at 20 months were 0.772 (0.890) at 6 (12) months, compared to 0.915 (0.962) for
      Griffiths scores. By contrast, EMPP and Griffiths scores had equal power to
      predict unability to walk unaided at 2 years of age (EMPP 6/12 months:
      0.946/0.983; Griffiths 6/12 months: 0.935/0.985). CONCLUSION: Neurological
      examinations with the EMPP at 6 and 12 months corrected age are of limited value
      to predict neurodevelopmental impairment at 20 months.

PMID- 20055778
TI  - Skin and soft tissue infections caused by community-associated methicillin
      resistant staphylococcus aureus among children in China.
AB  - AIM: To investigate the characteristic of community-associated methicillin
      resistant staphylococcus aureus (CA-MRSA) skin and soft tissue infections (SSTIs)
      among children in China. METHODS: Forty-seven children with CA-MRSA SSTIs were
      enrolled in this study. Clinical information was collected and analysed. The
      strains from the children were analysed by multilocus sequence typing (MLST),
      staphylococcus cassette chromosome mec (SCCmec) typing and spa typing. The Panton
      Valentine leukocidin (PVL) gene was also detected. RESULTS: The majority of the
      47 cases were impetigo (20; 42.6%) and abscesses (14; 29.8%). The rest was
      cellulites, infected wounds, omphalitis, paronychia and conjunctivitis combined
      folliculitis. Thirty-two of the isolates (68.1%) were PVL-positive, and the
      abscesses infected with PVL-positive strains usually required incision and
      drainage (87.5% vs. 16.7%, p = 0.026). Most of the isolates belonged to ST type
      59, which accounted for 46.8%, followed by ST1 (7/47, 14.9%) and ST910 (5/47,
      10.6%). The clone of ST59-MRSA-IV with t437 was the most prevalent one. The
      multiresistant rate of these strains was 93.6%. CONCLUSION: The most common
      disease of CA-MRSA SSTIs was impetigo, and PVL-positive abscess was associated
      with incision and drainage. ST59-MRSA-IV with t437 was the most prevalent clone,
      and the multiresistant rate was high in Chinese children.

PMID- 20055779
TI  - Diagnostic performance of urine dipstick testing in children with suspected UTI:
      a systematic review of relationship with age and comparison with microscopy.
AB  - BACKGROUND: Prompt diagnosis of urinary tract infection (UTI) in children is
      needed to initiate treatment but is difficult to establish without urine testing,
      and reliance on culture leads to delay. Urine dipsticks are often used as an
      alternative to microscopy, although the diagnostic performance of dipsticks at
      different ages has not been established systematically. METHOD: Studies comparing
      urine dipstick testing in infants versus older children and urine dipstick versus
      microscopy were systematically searched and reviewed. Meta-analysis of available
      studies was conducted. RESULTS: Six studies addressed these questions. The
      results of meta-analysis showed that the performance of urine dipstick testing
      was significantly less in the younger children when compared with older children
      (p < 0.01). Positive likelihood ratio (LR) of both nitrite and leucocyte positive
      38.54 [95% confidence interval (CI) 22.49-65.31], negative LR for both negative
      0.13 (95% CI 0.07-0.25) are reasonably good, and those for young infants are less
      reliable [positive LR 7.62 (95% CI 0.95-51.85) and negative LR 0.34 (95% CI 0.66
      0.15)]. Comparing microscopy and urine dipstick testing, using bacterial colony
      count on urine culture showed no significant difference between the two methods.
      CONCLUSION: Urine dipstick testing is more effective for diagnosis of UTI in
      children over 2 years than for younger children.

PMID- 20055780
TI  - Parents' views of their child's health and family function in paediatric
      inflammatory bowel disease.
AB  - AIM: The aim of this study was to explore parents' views and agreement of their
      child's current and future health, as well as the family's functioning in daily
      life with inflammatory bowel disease (IBD). METHODS: In this study, 119 parents
      (65 mothers and 54 fathers) of 66 adolescents (11-16 years) with IBD completed a
      questionnaire regarding their views of their child's IBD and health-related
      behaviour. RESULTS: The majority of the parents held a positive view of their
      child's current health status. However, the parents voiced a range of worries
      about their children's future health and life situation such as fear about the
      side effects of medication, concerns for future schooling, social life and
      employment options. Within the families, the parental pairs had more similar
      views about their child's current health status than about their future health.
      Factors that affected the parents' views consisted of cohabitation status, i.e.
      parents not living together, and severe disease course, both correlated with a
      more negative view of the child's current health and family functioning.
      CONCLUSION: The majority of the parents in this study had a largely positive view
      of their child's current health status, but they expressed concerns about their
      child's future health. Knowledge about parents' thoughts may be of importance for
      healthcare teams supporting families with IBD.

PMID- 20055781
TI  - Neonatal liver failure and haemophagocytic lymphohistiocytosis caused by a new
      perforin mutation.
AB  - Acute liver failure is a rare heterogeneous syndrome in neonates. We report of a
      newborn with haemophagocytic lymphohistiocytosis presenting as acute liver
      failure. Pancytopenia and multi-organ failure occurred later in the course. He
      carried two mutations of the perforin gene (PRF-1), one of which not previously
      described, causing a complete loss of perforin expression and natural killer cell
      function. CONCLUSION: Perforin expression and function should be promptly
      assessed in neonatal/infantile acute liver failure, as haemophagocytic
      lymphohistiocytosis requires specific treatment and represents a contra
      indication to liver transplant.

PMID- 20055782
TI  - Effectiveness of erdosteine, a second generation mucolytic agent, in children
      with acute rhinosinusitis: a randomized, placebo controlled, double-blinded
      clinical study.
AB  - AIM: To evaluate whether mucolytic agents have an adjuvant role with antibiotics
      in the treatment of children with rhinosinusitis. METHODS: Ninety-two children
      with rhinosinusitis were recruited for this randomized, placebo controlled,
      double-blinded clinical trial. Mean age was 8.5 +/- 3.2 years. Erdosteine (5-8
      mg/kg/day) was administered to 49 children, and 43 children received placebo.
      Changes in symptoms were recorded with the standard S5 scoring for 14 days.
      Complete resolution of symptoms on day 14 was considered to be clinical
      improvement. RESULTS: Eighty-one participants completed the study. Forty-one were
      in the treatment group and 40 in the placebo group. The average S5 scoring value
      at the onset of study was 11.0 in treatment group and 12.1 in placebo group. On
      day 14, mean scores were 3.1 in the treatment group and 2.8 in the placebo group.
      Complete improvement was 78% in the treatment group and 74.4% in the placebo
      group. There was no significant difference between the groups. There were no
      clinically detected serious side effects or complications in both groups.
      CONCLUSION: Use of erdosteine as a mucolytic agent in children with acute
      rhinosinusitis does not directly affect the success of treatment.

PMID- 20055783
TI  - Breastfeeding perceptions in communities in Mangochi district in Malawi.
AB  - AIM: To investigate mothers' perceptions of breastfeeding and influences from
      their social network. METHODS: A cross-sectional survey was carried out in
      Mangochi district, Malawi where questionnaire data from 157 rural and 192 semi
      urban mother-infant pairs were obtained. RESULTS: The proportion of mothers who
      thought that exclusive breastfeeding should last for 6 months and those who
      reported to have actually exclusively breastfed were 40.1% and 7.5% respectively.
      Of those who reported practising exclusive breastfeeding for 6 months, 77.5%
      stated that exclusive breastfeeding should last for 6 months. This opinion was
      independently associated with giving birth in a Baby-Friendly facility, OR =
      5.22; 95% CI (1.92-14.16). Among the mothers who thought that exclusive
      breastfeeding should last for less than 6 months, 43.9% reported having been
      influenced in their opinion by health workers. Infant crying was the most common
      (62.4%) reason for stopping exclusive breastfeeding. CONCLUSION: The findings
      illustrate the positive impact health workers can have, as well as the need to
      raise awareness of the benefits of exclusive breastfeeding among both health
      workers and mothers. Furthermore, continued counselling of mothers on how to deal
      with stressful infant behaviour such as crying may assist to prolong exclusive
      breastfeeding.

PMID- 20055784
TI  - Systematic review: the effects of carbonated beverages on gastro-oesophageal
      reflux disease.
AB  - BACKGROUND: Carbonated beverages have unique properties that may potentially
      exacerbate gastro-oesophageal reflux disease (GERD), such as high acidity and
      carbonation. Cessation of carbonated beverage consumption is commonly recommended
      as part of lifestyle modifications for patients with GERD. AIMS: To evaluate the
      relationship of carbonated beverages with oesophageal pH, oesophageal motility,
      oesophageal damage, GERD symptoms and GERD complications. METHODS: A systematic
      review. RESULTS: Carbonated beverage consumption results in a very short decline
      in intra-oesophageal pH. In addition, carbonated beverages may lead to a
      transient reduction in lower oesophageal sphincter basal pressure. There is no
      evidence that carbonated beverages directly cause oesophageal damage. Carbonated
      beverages have not been consistently shown to cause GERD-related symptoms.
      Furthermore, there is no evidence that these popular drinks lead to GERD
      complications or oesophageal cancer. CONCLUSIONS: Based on the currently
      available literature, it appears that there is no direct evidence that carbonated
      beverages promote or exacerbate GERD.

PMID- 20055785
TI  - Meta-analysis: targeting the intestinal microbiota in prophylaxis for post
      operative Crohn's disease.
AB  - BACKGROUND: Enteric bacteria play an important early role in the pathogenesis of
      Crohn's disease. AIM: To perform a meta-analysis of trials testing antibiotics or
      probiotics for prevention of post-operative recurrence of Crohn's disease.
      METHODS: Review of all randomized controlled trials comparing antibiotics or
      probiotics with placebo in prevention of endoscopic or clinical recurrence of
      Crohn's disease after surgical resection. Fixed-effect meta-analysis was
      performed with dichotomous data summarized using relative risk with 95%
      confidence intervals, where appropriate. RESULTS: Seven studies were identified
      as suitable for inclusion (two comparing antibiotics with placebo, five comparing
      probiotics with placebo). The use of nitroimidazole antibiotics (metronidazole,
      ornidazole) reduced the risk of clinical (RR 0.23; 95% CI 0.09-0.57, NNT = 4) and
      endoscopic (RR 0.44; 95% CI 0.26-0.74, NNT = 4) recurrence relative to placebo.
      However, these agents were associated with higher risk of adverse events (RR
      2.39, 95% CI 1.5-3.7) and patient withdrawal. Probiotic administration was not
      associated with any significant difference in risk of recurrence compared with
      placebo. CONCLUSIONS: Nitroimidazole antibiotics are effective in the prevention
      of post-operative Crohn's disease recurrence, but their side-effects limit
      acceptability. Probiotics have failed to show efficacy for post-operative
      prophylaxis, but may merit further study.

PMID- 20055786
TI  - Suppression of natural killer cell cytotoxicity in postpartum women.
AB  - PROBLEM: Natural Killer (NK) cell numbers and cytotoxicity are suppressed during
      pregnancy. Little is known about postpartum NK number and function. METHOD OF
      STUDY: Postpartum women (n = 39) were studied at one week and then monthly over
      the first six postpartum months. The standard natural killer cell cytotoxicity
      assay (NKCA) was performed. This is a Cr51 release assay from K562 cells cultured
      with peripheral blood mononuclear cells (PBMCs). RESULTS: Data indicate
      suppression of NK cytotoxicity in postpartum women. Cytotoxicity at each
      effector:target (E:T) ratio showed a drop from 1 week postpartum, reaching a
      nadir at around 2 months, and a trend towards recovery of cytotoxicity from 3 to
      6 months. Lytic units (LUs) from pre-incubated cells from postpartum women were
      lower than age-matched, non-pregnant, non-postpartum controls through the fifth
      postpartum month. CONCLUSION: These data suggest that the postpartum period, like
      pregnancy, is characterized by decreased NK cytotoxicity activity. This
      suppressed NK cytotoxic effect may result as a response to interaction with
      tolerized fetal microchimeric cells accumulated during pregnancy in maternal
      blood and tissues.

PMID- 20055787
TI  - Expression of IL-6, IL-8, TNF-alpha, IL-10, HSP-60, anti-HSP-60 antibodies, and
      anti-sperm antibodies, in semen of men with leukocytes and/or bacteria.
AB  - PROBLEM: Different cellular and biochemical markers have been proposed as
      indicators of infection-inflammation of male genital tract. METHOD OF STUDY:
      Semen samples from 80 men attending an andrologic clinic were evaluated to
      determine the presence of leukocyte, bacteria, antibodies against Chlamydia
      trachomatis, levels of IL-6, IL-8, IL-10, and TNF-alpha, HSP-60, anti-HSP-60
      antibodies, and anti-sperm antibodies. RESULTS: Leukocytes in semen significantly
      correlated with an increase in IL-6, IL-8, and TNF-alpha. The simultaneous
      presence of pathogens and leukocytes was associated with high levels of IL-8 and
      TNF-alpha, whereas IL-6 was more associated with the presence of leukocytes. Anti
      HSP-60 antibodies positively correlated with IL-6 and IL-8. The presence of anti
      sperm antibodies highly associated with an increase in anti-HSP-60 antibodies.
      CONCLUSIONS: The type of cytokines present in the semen will depend on the single
      or simultaneous presence of leukocytes and/or pathogens. Chronic male genital
      tract infections could be associated with the development of anti-HSP-60
      antibodies and anti-sperm antibodies.

PMID- 20055788
TI  - Immunocontraceptive effect of DNA vaccine targeting fertilin beta in male mice.
AB  - PROBLEM: In previous study, two eukaryotic expression plasmids pSG.SS.YL
      F(beta.ECD) and pSG.SS.C3d3.YL-F(beta.ECD) were successfully constructed and
      transfected in HEK293 cells. Now, we want to evaluate the immunocontraceptive
      effect of these two DNA vaccines that target the extracellular domain
      (Fbeta.(ECD)) of sperm antigen fertilin beta subunit in Kunming male mice. METHOD
      OF STUDY: DNA vaccines pSG.SS.YL-F(beta.ECD) and pSG.SS.C3d3.YL-F(beta.ECD) were
      injected into Kunming male mice three times at 0, 4, and 8 weeks, respectively.
      An antifertility effect was observed. Serum antibody and cytokines were also
      detected. RESULTS: Both vaccines significantly decreased both the pregnancy rate
      and the number of newborns. The serum levels of IL-2 and INF-gamma significantly
      decreased, whereas the levels of IL-4 and IL-10 significantly increased. Compared
      with pSG.SS.YL-F(beta.ECD), pSG.SS.C3d3.YL-F(beta.ECD) was more effective in
      birth control, and its specific F(beta)-IgG antibody titer in serum was
      significantly higher and longer. CONCLUSION: The results indicate that both
      pSG.SS.YL-F(beta.ECD) and pSG.SS.C3d3.YL-F(beta.ECD) DNA vaccines are effective
      in birth control of mice. The immunocontraceptive effect of F(beta.ECD) DNA
      vaccine in male mice is improved with the addition of immuno-adjuvant C3d3.

PMID- 20055789
TI  - Effects of cyclic versus sustained estrogen administration on peripheral immune
      functions in ovariectomized mice.
AB  - PROBLEM: Estrogens have multiple influences on immune functions. We aimed to
      compare the effects of cyclic versus sustained estrogen treatments under the same
      accumulated dose on peripheral immune functions in ovariectomized mice. METHOD OF
      STUDY: Ovariectomized adult Balb/c mice were treated with estradiol (E2) by s.c.
      injection once every 4 days (total 44.8 microg) or by pellet implantation (total
      44.2 microg). After 6 weeks of treatment, all animals were immunized with DNP
      KLH. Peripheral immune functions were assessed 10 days later. RESULTS: Both
      cyclic and sustained E2 treatments significantly reduced the percentage of
      splenic B220(+)sIgM(+) cells, enhanced IFN-gamma production and suppressed IL-6
      secretion from Con A-stimulated splenocytes, and increased serum anti-DNP
      antibody levels. No differences were found in the above responses or in uterine
      weight gain between the two regimens of E2 administration. CONCLUSION: There are
      no differential effects on peripheral immune functions between cyclic and
      sustained estrogen administration under the same total dose.

PMID- 20055790
TI  - Transforming growth factor-beta 1 gene polymorphisms in Korean patients with pre
      eclampsia.
AB  - PROBLEM: The aim of this study was to investigate whether c.869T>C (Leu10Pro) and
      c.915G>C (Arg25Pro) polymorphisms in exon1 of the transforming growth factor
      beta1 (TGF-beta1) gene are associated with development of pre-eclampsia (PE) in
      Korean women. METHOD OF STUDY: We analyzed blood samples from 164 patients with
      PE and 182 healthy pregnant women using the polymerase chain reaction and DNA
      sequencing. RESULTS: The frequencies of the 869CC and combined TC/CC genotypes
      were higher in patients with PE than in healthy controls. In the PE with
      intrauterine growth restriction (IUGR), the frequencies of these genotypes were
      also higher than that in controls. Furthermore, the 869C allele frequency was
      significantly higher in both PE and IUGR-complicated PE than in controls.
      Multivariate analysis showed that the 869TC, CC, and combined TC/CC genotypes
      were associated with an increased risk of PE compared with the 869TT genotype. In
      addition, the 869TC, CC, and combined TC/CC genotypes were significantly
      associated with an increased risk of IUGR-complicated PE compared with the 869TT
      genotype. The TGF-beta1 c.915G>C polymorphism was not detected in our population.
      CONCLUSION: Our findings indicate that the TGF-beta1 c.869T>C polymorphism may be
      a genetic risk factor for PE and IUGR-complicated PE.

PMID- 20055791
TI  - The unique properties of uterine NK cells.
AB  - Natural killer (NK) cells are lymphocytes of the innate immunity system that are
      able to kill various hazardous pathogens and tumors. However, it is now widely
      accepted that NK cells also possess non-destructive functions, as has been
      demonstrated for uterine NK cells. Here, we review the unique properties of the
      NK cells in the uterine mucosa, prior to and during pregnancy. We discuss the
      phenotype and function of mouse and human endometrial and decidual NK cells and
      suggest that the major function of decidual NK cells is to assist in fetal
      development. We further discuss the origin of decidual NK cells and suggest
      several possibilities that might explain their accumulation in the decidua during
      pregnancy.

PMID- 20055792
TI  - The persistence of paternal antigens in the maternal body is involved in
      regulatory T-cell expansion and fetal-maternal tolerance in murine pregnancy.
AB  - PROBLEM: Mammalian pregnancy is a state of immunological tolerance and CD4(+)
      CD25(+) regulatory T cells (Treg) contribute to its maintenance. Knowing that
      Treg act in an antigen-specific way during pregnancy, we hypothesized that they
      are generated after maternal immune cells encounter paternal antigens. METHOD OF
      STUDY: We mated wild type females with transgenic green fluorescent protein (GFP)
      males in an allogenic setting and killed them on different days of pregnancy.
      RESULTS: Presence of paternal and maternal MHC class II(+) cells in vaginal
      lavage on day 0.5 of pregnancy was confirmed. Thus, antigen presentation may take
      place early during pregnancy in the periphery either by the direct or indirect
      pathways. Foxp3(+) cells known to have regulatory activity could be detected on
      day 2 of pregnancy in lymph nodes and shortly after implantation at the fetal
      maternal interface. CONCLUSION: Our data suggest that paternal antigens are
      processed early during pregnancy, which leads to the generation of Treg. The
      continuous release of placental antigens into the maternal circulation allows the
      maintenance of a Treg population which is specific for paternal antigens and
      mediates tolerance toward the semi-allogeneic fetus until the time point of
      birth.

PMID- 20055793
TI  - Clinical predictors of proteinuria after conversion to sirolimus in kidney
      transplant recipients.
AB  - Proteinuria is an increasingly recognized effect of sirolimus (SRL) therapy in
      kidney transplant recipients. Predictors of proteinuria after conversion to SRL
      are not well described, and in particular the risk in African-American (AA)
      kidney recipients is unknown. We sought to analyze risk factors for proteinuria
      with SRL therapy in a cohort of 39 patients (44% AA) converted from tacrolimus to
      SRL at a mean time of 4 months posttransplantation. Patients were maintained on
      therapy with mycophenolate mofetil while most patients underwent early steroid
      withdrawal. Urinary protein to creatinine ratio (Up/cr) at a mean of 14 months
      postconversion increased to > or =500 mg/g in 65% of AAs versus 14% of non-AAs (p
      = 0.001). Mean arterial blood pressure at the time of conversion and
      pretransplant proteinuric kidney disease were also predictors of proteinuria
      after SRL conversion. In conclusion, AAs appear to be at high risk for
      proteinuria and should be monitored closely after conversion to SRL in
      calcineurin inhibitor sparing protocols.

PMID- 20055794
TI  - Cluster analysis of lesions in nonselected kidney transplant biopsies:
      microcirculation changes, tubulointerstitial inflammation and scarring.
AB  - Banff classification empirically established scoring of histologic lesions, but
      the relationships of lesions to each other and to underlying biologic processes
      remain unclear. We hypothesized that class discovery tools would reveal new
      relationships between individual lesions, and relate lesions to C4d staining,
      anti-HLA donor-specific antibody (DSA) and time posttransplant. We studied 234
      nonselected renal allograft biopsies for clinical indications from 173 patients.
      Silhouette plotting and principal component analysis revealed three groups of
      lesions: microcirculation changes, including inflammation (glomerulitis,
      capillaritis) and deterioration (double contours, mesangial expansion);
      scarring/hyalinosis; and tubulointerstitial inflammation. DSA and C4d grouped
      with microcirculation inflammation, whereas time posttransplant grouped with
      scarring/hyalinosis lesions. Intimal arteritis clustered with DSA, C4d and
      microcirculation inflammation, but also showed correlations with tubulitis.
      Fibrous intimal thickening in arteries clustered with scarring/hyalinosis.
      Capillary basement membrane multilayering showed intermediary relationships
      between microcirculation deterioration and time-dependent scarring. Correlation
      analysis and hierarchical clustering confirmed the lesion relationships. Thus, we
      propose that the pathologic lesions in biopsies are not independent but are
      members of groups that represent distinct pathogenic forces: microcirculation
      changes, reflecting the stress of DSA; scarring, hyalinosis and arterial
      fibrosis, reflecting the cumulative burden of injury over time; and
      tubulointerstitial inflammation. Interpretation of lesions should reflect these
      associations.

PMID- 20055795
TI  - Efficient utilization of the expanded criteria donor (ECD) deceased donor kidney
      pool: an analysis of the effect of labeling.
AB  - We investigated the effect of the expanded criteria donor (ECD) label on (i)
      recovery of kidneys and (ii) acceptance for transplantation given recovery. An
      ECD is age > or = 60, or age 50-59 with > or = 2 of 3 specified comorbidities.
      Using data from the Scientific Registry of Transplant Recipients from 1999 to
      2005, we modeled recovery rates through linear regression and transplantation
      probabilities via logistic regression, focusing on organs from donors just
      younger versus just-older than the ECD age thresholds. We split the sample at
      July 1, 2002 to determine how decisions changed at the approximate time of
      implementation of the ECD definition. Before July 2002, the number of recovered
      kidneys with 0-1 comorbidities dropped at age 60, but transplantation
      probabilities given recovery did not. After July 2002, the number of recovered
      kidneys with 0-1 comorbidities rose at age 60, but transplantation probabilities
      contingent on recovery declined. No similar trends were observed at donor age 50
      among donors with > or = 2 comorbidities. Overall, implementation of the ECD
      definition coincided with a reversal of an apparent reluctance to recover kidneys
      from donors over age 59, but increased selectiveness on the part of
      surgeons/centers with respect to these kidneys.

PMID- 20055796
TI  - Diabetes mellitus: a risk factor for delayed graft function after deceased donor
      kidney transplantation.
AB  - Early graft function is a major determinant of long-term outcomes after renal
      transplantation. Recently, recipient diabetes was identified as a risk factor for
      poor initial graft function in living donor renal transplantation. To further
      explore this association, we performed a paired analysis of deceased donor renal
      transplants from January 1994 to December 2005. A total of 25,523 transplant
      pairs were analyzed via conditional logistic regression. Diabetic recipients were
      older (53.16 vs. 46.75 years, p < 0.01), had a lower average panel reactive
      antibody (12% vs. 15%, p < 0.01) and fewer prior transplants (0.07 vs. 0.12, p <
      0.01). Recipient diabetes, age, male gender, African American race, elevated peak
      panel reactive antibody and increased cold ischemia time were independent risk
      factors for delayed graft function. Specifically, diabetic recipients had
      increased risk of DGF on univariate analysis (odds ratio [OR] 1.32, 95%
      confidence interval [CI] 1.23-1.42, p < 0.01). Multivariable analysis confirmed
      this association but the risk differed by recipient gender; with diabetes having
      a greater effect in women (OR 1.66, 95% CI 1.45-1.91, p < 0.01) compared to men
      (OR 1.28, 95% CI 1.15-1.43, p < 0.01). It is unknown whether the deleterious
      impact of recipient diabetes on graft function after renal transplantation
      results from perioperative hyperglycemia or the chronic sequelae of diabetes.

PMID- 20055797
TI  - Incidence of and risk factors for posttransplant diabetes mellitus after pancreas
      transplantation.
AB  - Posttransplant diabetes mellitus (PTDM) after pancreas transplantation (PTX) has
      not been extensively examined. This single center, retrospective analysis of 674
      recipients from 1994 to 2005 examines the incidence of and risk factors for PTDM
      after PTX. PTDM was defined by fasting plasma glucose level > or =126 mg/dL,
      confirmed on a subsequent measurement or treatment with insulin or oral
      hypoglycemic agent for > or =30 days. The incidence of PTDM was 14%, 17% and 25%
      at 3, 5 and 10 years after PTX, respectively and was higher (p = 0.01) in
      solitary pancreas (PAN) versus simultaneous kidney pancreas (SPK) recipients
      (mean follow-up 6.5 years). In multivariate analysis, factors associated with
      PTDM were: older donor age (hazard ratio [HR] 1.04, 95% confidence interval [CI]
      1.03-1.06, p < 0.001), higher recipient body mass index (HR 1.07,CI 1.01-1.13, p
      = 0.01), donor positive/recipient negative CMV status (HR 1.65,CI 1.03-2.6, p =
      0.04), posttransplant weight gain (HR 4.7,CI 1.95-11.1, p < 0.001), pancreas
      rejection (HR 1.94.CI 1.3-2.9, p < 0.001) and 6 month fasting glucose (HR 1.01,CI
      1.01-1.02, p < 0.001), hemoglobin A(1)c, (HR 1.12,CI 1.05-1.22, p = 0.002) and
      triglyceride to high-density lipoprotein (TG/HDL) ratio (HR 0.94,CI 0.91-0.96, p
      < 0.001). This study delineates the incidence and identifies risk factors for
      PTDM after PTX.

PMID- 20055799
TI  - Liver transplantation with grafts from controlled donors after cardiac death: a
      20-year follow-up at a single center.
AB  - The first liver transplantation (LTx) in Sweden was performed in 1984, but brain
      death as a legal death criterion was not accepted until 1988. Between November
      1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty-four
      grafts were from donors after cardiac death (DCD) and 16 grafts from heart
      beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary
      complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively).
      Graft and patient survival did not differ between the groups. In the total group,
      there was a significant difference in graft survival between first-time LTx
      grafts and grafts used for retransplantation. There was better graft survival in
      nonmalignant than malignant patients, although this did not reach statistical
      significance. Multivariate analysis revealed cold ischemia time and post-LTx peak
      ALT to be independent predictive factors for graft survival in the DCD group. In
      the 11 livers surviving 20 years or more, follow-up biopsies were performed 18-20
      years post-LTx (n = 10) and 6 years post-LTx (n = 1). Signs of chronic rejection
      were seen in three cases, with no difference between DCD and HBD. Our analysis
      with a 20-year follow-up suggests that controlled DCD liver grafts might be a
      feasible option to increase the donor pool.

PMID- 20055798
TI  - Anti-inflammatory and anticoagulant effects of transgenic expression of human
      thrombomodulin in mice.
AB  - Thrombomodulin (TBM) is an important vascular anticoagulant that has species
      specific effects. When expressed as a transgene in pigs, human (h)TBM might
      abrogate thrombotic manifestations of acute vascular rejection (AVR) that occur
      when GalT-KO and/or complement regulator transgenic pig organs are transplanted
      to primates. hTBM transgenic mice were generated and characterized to determine
      whether this approach might show benefit without the development of deleterious
      hemorrhagic phenotypes. hTBM mice are viable and are not subject to spontaneous
      hemorrhage, although they have a prolonged bleeding time. They are resistant to
      intravenous collagen-induced pulmonary thromboembolism, stasis-induced venous
      thrombosis and pulmonary embolism. Cardiac grafts from hTBM mice to rats treated
      with cyclosporine in a model of AVR have prolonged survival compared to controls.
      hTBM reduced the inflammatory reaction in the vein wall in the stasis-induced
      thrombosis and mouse-to-rat xenograft models and reduced HMGB1 levels in LPS
      treated mice. These results indicate that transgenic expression of hTBM has
      anticoagulant and antiinflammatory effects that are graft-protective in murine
      models.

PMID- 20055800
TI  - Improving organ procurement travel practices in the United States: proceedings
      from the Michigan Donor Travel Forum.
AB  - There are significant risks and inefficiencies associated with organ procurement
      travel. In an effort to identify, quantify, and define opportunities to mitigate
      these risks and inefficiencies, 25 experts from the transplantation,
      transportation and insurance fields were convened. The forum concluded that: on
      procurement travel practices are inadequate, there is wide variation in the
      quality of aero-medical transportation, current travel practices for organ
      procurement are inefficient and there is a lack of standards for organ
      procurement travel liability coverage. The forum concluded that the transplant
      community should require that air-craft vendors adhere to industry quality
      standards compatible with the degree of risk in their mission profiles. Within
      this context, a purchasing collaborative within the transplant community may
      offer opportunities for improved service and safety with lower costs. In
      addition, changes in travel practices should be considered with broader sharing
      of procurement duties across centers. Finally, best practice standards should be
      instituted for life insurance for transplant personnel and liability insurance
      for providers. Overall, the aims of these proposals are to raise procurement
      travel standards and in doing so, to improve the transplantation as a whole.

PMID- 20055801
TI  - Understanding disparities in transplantation: do social networks provide the
      missing clue?
AB  - Although the National Organ Transplant Act calls for equity in access to
      transplantation, scarcity and racial disparities persist. To date, even the most
      comprehensive models have been unable to adequately explain these racial
      disparities, leaving policymakers unsure how best to intervene. Previous
      individual-level analyses, which have implicated risk factors such as race,
      financial status, cultural beliefs, unemployment, lack of commitment to surgery
      and lack of continuous access to care, overlook contextual and social network
      exposures. Social networks present a compelling way to examine cumulative risk
      clustered across individuals. Social networks have been shown to influence health
      outcomes and health behaviors through various pathways, including shared social
      capital, engaging in similar or group risky behaviors, diffusion of information
      and adopting or propagating social norms. Precursors to chronic kidney disease,
      including obesity, have been shown to spread through social networks. Social
      network analysis can reveal shared risks between potential donors and recipients
      in a given network, clarifying the likelihood of finding an appropriate match
      through either direct donation or paired exchanges. This paper presents a novel
      application of social network analysis to transplantation, illustrating
      implications for disparities and future clinical interventions.

PMID- 20055802
TI  - Multicenter analysis of novel and established variables associated with
      successful human islet isolation outcomes.
AB  - Islet transplantation is a promising therapy used to achieve glycometabolic
      control in a select subgroup of individuals with type I diabetes. However,
      features that characterize human islet isolation success prior to transplantation
      are not standardized and lack validation. We conducted a retrospective analysis
      of 806 isolation records from 14 pancreas-processing laboratories, considering
      variables from relevant studies in the last 15 years. The outcome was defined as
      post-purification islet equivalent count, dichotomized into yields > or =315 000
      or < or =220 000. Univariate analysis showed that donor cause of death and use of
      hormonal medications negatively influenced outcome. Conversely, pancreata from
      heavier donors and those containing elevated levels of surface fat positively
      influence outcome, as did heavier pancreata and donors with normal amylase
      levels. Multivariable logistic regression analysis identified the positive impact
      on outcome of surgically intact pancreata and donors with normal liver function,
      and confirmed that younger donors, increased body mass index, shorter cold
      ischemia times, no administration of fluid/electrolyte medications, absence of
      organ edema, use of University of Wisconsin preservation solution and a fatty
      pancreas improves outcome. In conclusion, this multicenter analysis highlights
      the importance of carefully reviewing all donor, pancreas and processing
      parameters prior to isolation and transplantation.

PMID- 20055803
TI  - Decay accelerating factor is essential for successful corneal engraftment.
AB  - In contrast to immune restrictions that pertain for solid organ transplants, the
      tolerogenic milieu of the eye permits successful corneal transplantation without
      systemic immunosuppression, even across a fully MHC disparate barrier. Here we
      show that recipient and donor expression of decay accelerating factor (DAF or
      CD55), a cell surface C3/C5 convertase regulator recently shown to modulate T
      cell responses, is essential to sustain successful corneal engraftment. Whereas
      wild-type (WT) corneas transplanted into multiple minor histocompatibility
      antigen (mH), or HY disparate WT recipients were accepted, DAF's absence on
      either the donor cornea or in the recipient bed induced rapid rejection. Donor or
      recipient DAF deficiency led to expansion of donor-reactive IFN-gamma producing
      CD4(+) and CD8(+) T cells, as well as inhibited antigen-induced IL-10 and TGF
      beta, together demonstrating that DAF deficiency precludes immune tolerance. In
      addition to demonstrating a requisite role for DAF in conferring ocular immune
      privilege, these results raise the possibility that augmenting DAF levels on
      donor corneal endothelium and/or the recipient bed could have therapeutic value
      for transplants that clinically are at high risk for rejection.

PMID- 20055804
TI  - The outcome of patients with nephrogenic systemic fibrosis after successful
      kidney transplantation.
AB  - Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with
      severely diminished kidney function. Currently, no standard treatment exists but
      improvement has been reported after restoration of kidney function. We
      retrospectively studied 17 NSF patients with and without successful kidney
      transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx
      developed NSF pretransplant whereas two developed NSF immediately after KTx with
      delayed graft function. Two of the six dialysis patients had previous failed
      kidney transplants. Age and sex were well matched. All but one patient was
      dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx
      patients and 9 months for dialysis patients. Kidney transplants achieved adequate
      renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a
      glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6%
      of the transplanted patients and 50% of the nontransplanted patients (p = 0.86).
      Two KTx patients had complete resolution of their symptoms whereas four had
      partial improvement. Improvement in the dialysis patients was all partial.
      Successful KTx did not insure improvement in NSF and in fact appeared to have no
      significant benefit over dialysis.

PMID- 20055806
TI  - Concomitant endothelin-1 overexpression in lung transplant donors and recipients
      predicts primary graft dysfunction.
AB  - Primary graft dysfunction (PGD) causes significant morbidity following lung
      transplantation (LTX). Mortality is high in PGD and therapeutic strategies are
      limited. To investigate whether endothelin-1 (ET-1) that mediates increased
      vascular permeability and edema formation in lung grafts can predict PGD, ET-1
      mRNA expression was examined in lung tissue biopsies of 105 donors and recipients
      obtained shortly before LTX. Serum ET-1 concentration was assessed by ELISA. PGD
      grade was diagnosed and scored by oxygenation and radiological characteristics
      according to ISHLT guidelines. PGD grade 3 developed in 11% of patients. ET-1
      mRNA expression was significantly increased in both donor (p < 0.0001) and
      recipient (p = 0.01) developing PGD as compared to no PGD group. Pretransplant ET
      1 serum concentrations were elevated in recipients with PGD as compared to no PGD
      group (p < 0.0001), although serum ET-1 was not different between donors whose
      grafts developed PGD grades 0-3. In regression analysis, concomitant elevated
      donor tissue ET-1 and recipient serum ET-1 predicted PGD grade 3. This study
      indicates that pretransplant ET-1 mRNA overexpression in donors associated with
      elevated pretransplant serum ET-1 in recipients contribute to PGD development and
      that their assessment might be beneficial to predict PGD and to identify
      recipients who could benefit from a targeted ET-1 blockade.

PMID- 20055805
TI  - Complement independent antibody-mediated endarteritis and transplant arteriopathy
      in mice.
AB  - Complement fixation, as evidenced by C4d in the microvasculature, is a widely
      accepted criterion of antibody-mediated rejection. Complement fixation has been
      shown to be essential in acute antibody-mediated rejection, but its role in
      chronic rejection has not been addressed. Previous studies showed that passive
      transfer of complement fixing monoclonal IgG2a anti-H-2Kk into B6.RAG1-/- KO
      recipients of B10.BR hearts led to progressive chronic transplant arteriopathy
      (CTA) over 14-28 days, accompanied by C4d deposition. The present studies were
      designed to test whether complement was required for these lesions. We report
      that a noncomplement fixing donor-specific alloantibody (DSA, monoclonal IgG1
      anti-H-2Kk) injected into B6.RAG1-/- KO recipients of B10.BR hearts also promotes
      CTA, without C4d deposition. Furthermore, a passive transfer of DSA (monoclonal
      IgG2a anti-H-2Kk) initiated endarteritis followed by CTA in B6.RAG1-/- mice
      genetically deficient in the third component of complement (RAG1-/-C3-/-). These
      studies indicate that antibody to class I MHC antigens can trigger chronic
      arterial lesions in vivo without complement participation, in contrast to acute
      antibody-mediated rejection. This pathway may be relevant to C4d-negative chronic
      rejection sometimes observed in patients with DSA, and argues that lack of C4d
      deposition does not exclude antibody-mediated chronic rejection.

PMID- 20055807
TI  - What defines a transplant surgeon? A needs assessment for curricular development
      in transplant surgery fellowship training.
AB  - This study compares the perceptions of transplant surgery program directors (PDs)
      and recent fellowship graduates (RFs) regarding the adequacy of training and
      relevancy to practice of specific curricular content items in fellowship
      training. Surveys were sent to all American Society of Transplant Surgery
      approved fellowship PDs and all RFs in practice <5 years. For operative
      procedures, the RFs considered the overall training to be less adequate than the
      PDs (p = 0.0117), while both groups considered the procedures listed to be
      relevant to practice (p = 0.8281). Regarding nonoperative patient care items,
      although RFs tended to rank many individual items lower, both groups generally
      agreed that the training was both adequate and relevant. For nonpatient care
      related items (i.e. transplant-related ethics, economics, research, etc.), both
      groups scored them low regarding their adequacy of training although RFs scored
      them significantly lower than PDs (p = 0.0006). Regarding their relevance to
      practice, while both groups considered these items relevant, RFs generally
      considered them more relevant than PDs. Therefore, although there is consensus on
      many items, significant differences exist between PDs and RFs regarding their
      perceptions of the adequacy of training and the relevance to practice of specific
      curriculum items in transplant surgery fellowship training.

PMID- 20055808
TI  - Tolerogenic dendritic cells: all present and correct?
AB  - Although well-recognized for their sentinel role and, when activated, their
      immunostimulatory function, bone marrow-derived dendritic cells (DC) possess
      inherent tolerogenic (tol) ability. Under quiescent conditions, these cells
      maintain central and peripheral self tolerance. When appropriately conditioned,
      in vitro or in vivo, they inhibit innate and adaptive immunity to foreign
      antigens, including memory T-cell responses. This suppressive function is
      mediated by various mechanisms, including the expansion and induction of antigen
      specific regulatory T cells. Extensive experience in rodent models and recent
      work in nonhuman primates, indicate the potential of pharmacologically-modified,
      tol DC (tolDC) to regulate alloimmunity in vivo and to promote lasting,
      alloantigen-specific T-cell unresponsiveness and transplant survival. While there
      are many questions yet to be addressed concerning the functional biology of tolDC
      in humans, these cells offer considerable potential as natural, safe and antigen
      specific regulators for long-term control of the outcome of organ and
      hematopoietic cell transplantation. This minireview surveys recent findings that
      enhance understanding of the functional biology and therapeutic application of
      tolDC, with special reference to transplantation.

PMID- 20055809
TI  - Pathological and clinical characterization of the 'troubled transplant': data
      from the DeKAF study.
AB  - We are studying two cohorts of kidney transplant recipients, with the goal of
      defining specific clinicopathologic entities that cause late graft dysfunction:
      (1) prevalent patients with new onset late graft dysfunction (cross-sectional
      cohort); and (2) newly transplanted patients (prospective cohort). For the cross
      sectional cohort (n = 440), mean time from transplant to biopsy was 7.5 +/- 6.1
      years. Local pathology diagnoses included CAN (48%), CNI toxicity (30%), and
      perhaps surprisingly, acute rejection (cellular- or Ab-mediated) (23%). Actuarial
      rate of death-censored graft loss at 1 year postbiopsy was 17.7%; at 2 years,
      29.8%. There was no difference in postbiopsy graft survival for recipients with
      versus without CAN (p = 0.9). Prospective cohort patients (n = 2427) developing
      graft dysfunction >3 months posttransplant undergo 'index' biopsy. The rate of
      index biopsy was 8.8% between 3 and 12 months, and 18.2% by 2 years. Mean time
      from transplant to index biopsy was 1.0 +/- 0.6 years. Local pathology diagnoses
      included CAN (27%), and acute rejection (39%). Intervention to halt late graft
      deterioration cannot be developed in the absence of meaningful diagnostic
      entities. We found CAN in late posttransplant biopsies to be of no prognostic
      value. The DeKAF study will provide broadly applicable diagnostic information to
      serve as the basis for future trials.

PMID- 20055810
TI  - Inflammation and epithelial to mesenchymal transition in lung transplant
      recipients: role in dysregulated epithelial wound repair.
AB  - Epithelial to mesenchymal transition (EMT) has been implicated in the
      pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although
      TNF-alpha accentuates TGF-beta1 driven EMT in primary human bronchial epithelial
      cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines
      elevated in the airways of patients with OB may also accentuate EMT and
      contribute to dysregulated epithelial wound repair. PBECs from lung transplant
      recipients were stimulated with TGF-beta1+/-IL-1beta, IL-8, TNF-alpha or
      activated macrophages in co-culture and EMT assessed. The quality and rate of
      wound closure in a standardized model of lung epithelial injury was assessed in
      response to above stimuli. Co-treatment with TGF-beta1+TNF-alpha or IL-1beta
      significantly accentuates phenotypic and some functional features of EMT compared
      to TGF-beta1 alone. Co-treatment with TGF-beta1+TNF-alpha or IL-1beta accelerates
      epithelial wound closure however the quality of repair is highly dysregulated. Co
      treatment with TGF-beta1+IL-8 has no significant effect on EMT or the speed or
      quality of wound healing. Activated macrophages dramatically accentuate TGF-beta1
      driven EMT and cause dysregulated wound repair. Crosstalk between macrophage
      derived acute inflammation in the airway and elevated TGF-beta1 may favor
      dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT.

PMID- 20055811
TI  - BK-virus and the impact of pre-emptive immunosuppression reduction: 5-year
      results.
AB  - A 1-year, single-center, randomized trial demonstrated that the calcineurin
      inhibitor or adjuvant immunosuppression, independently, does not affect BK
      viruria or viremia and that monitoring and pre-emptive withdrawal of
      immunosuppression was associated with resolution of BK-viremia and absence of
      clinical BK-nephropathy without acute rejection or graft loss. A retrospective 5
      year review of this trial was conducted. In cases of BK viremia, the
      antimetabolite was withdrawn and for sustained viremia, the calcineurin inhibitor
      was minimized. Five-year follow-up was available on 97% of patients. Overall 5
      year patient survival was 91% and graft survival was 84%. There were no
      differences in patient-survival by immunosuppressive regimen or presence of BK
      viremia. Immunosuppression and viremia did not influence graft survival. Acute
      rejection occurred in 12% by 5-years after transplant, was less common with
      tacrolimus versus cyclosporine (9% vs. 18%; p = 0.082), and was lowest with the
      tacrolimus-azathioprine regimen (5%, p = 0.127). Tacrolimus was associated with
      better renal function at 5-years (eGFR 63 FK vs. 52 CsA mL/min, p = 0.001).
      Minimization of immunosuppression upon detection of BK-viremia was associated
      with excellent graft survival at 5-years, low rejection rates and excellent renal
      function. It is a safe, short and long-term strategy that resulted in freedom
      from clinically evident BK-virus nephropathy.

PMID- 20055812
TI  - Modulation of brain dead induced inflammation by vagus nerve stimulation.
AB  - Because the vagus nerve is implicated in control of inflammation, we investigated
      if brain death (BD) causes impairment of the parasympathetic nervous system,
      thereby contributing to inflammation. BD was induced in rats. Anaesthetised
      ventilated rats (NBD) served as control. Heart rate variability (HRV) was
      assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during
      BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix
      chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on
      all organs. Serum was collected to assess TNFalpha concentrations. Renal
      transplantations were performed to address the influence of vagus nerve
      stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus
      nerve stimulation inhibited the increase in serum TNFalpha concentrations and
      resulted in down-regulation of a multiplicity of pro-inflammatory genes in
      intestinal tissue. In renal tissue vagal stimulation significantly decreased the
      expression of E-selectin, IL1beta and ITGA6. Renal function was significantly
      better in recipients that received a graft from a BD + STIM donor. Our study
      demonstrates impairment of the parasympathetic nervous system during BD and
      inhibition of serum TNFalpha through vagal stimulation. Vagus nerve stimulation
      variably affected gene expression in donor organs and improved renal function in
      recipients.

PMID- 20055813
TI  - The pattern of linkage disequilibrium in German Holstein cattle.
AB  - This study presents a second generation of linkage disequilibrium (LD) map
      statistics for the whole genome of the Holstein-Friesian population, which has a
      four times higher resolution compared with that of the maps available so far. We
      used DNA samples of 810 German Holstein-Friesian cattle genotyped by the Illumina
      Bovine SNP50K BeadChip to analyse LD structure. A panel of 40 854 (75.6%) markers
      was included in the final analysis. The pairwise r(2) statistic of SNPs up to 5
      Mb apart across the genome was estimated. A mean value of r(2) = 0.30 +/- 0.32
      was observed in pairwise distances of <25 kb and it dropped to 0.20 +/- 0.24 at
      50-75 kb, which is nearly the average inter-marker space in this study. The
      proportion of SNPs in useful LD (r(2) > or = 0.25) was 26% for the distance of 50
      and 75 kb between SNPs. We found a lower level of LD for SNP pairs at the
      distance < or =100 kb than previously thought. Analysis revealed 712 haplo-blocks
      spanning 4.7% of the genome and containing 8.0% of all SNPs. Mean and median
      block length were estimated as 164 +/- 117 kb and 144 kb respectively. Allele
      frequencies of the SNPs have a considerable and systematic impact on the estimate
      of r(2). It is shown that minimizing the allele frequency difference between SNPs
      reduces the influence of frequency on r(2) estimates. Analysis of past effective
      population size based on the direct estimates of recombination rates from SNP
      data showed a decline in effective population size to N(e) = 103 up to
      approximately 4 generations ago. Systematic effects of marker density and
      effective population size on observed LD and haplotype structure are discussed.

PMID- 20055815
TI  - A meta-analysis of dispersal in butterflies.
AB  - Dispersal has recently gained much attention because of its crucial role in the
      conservation and evolution of species facing major environmental changes such as
      habitat loss and fragmentation, climate change, and their interactions.
      Butterflies have long been recognized as ideal model systems for the study of
      dispersal and a huge amount of data on their ability to disperse has been
      collected under various conditions. However, no single 'best' method seems to
      exist leading to the co-occurrence of various approaches to study butterfly
      mobility, and therefore a high heterogeneity among data on dispersal across this
      group. Accordingly, we here reviewed the knowledge accumulated on dispersal and
      mobility in butterflies, to detect general patterns. This meta-analysis
      specifically addressed two questions. Firstly, do the various methods provide a
      congruent picture of how dispersal ability is distributed across species?
      Secondly, is dispersal species-specific? Five sources of data were analysed:
      multisite mark-recapture experiments, genetic studies, experimental assessments,
      expert opinions, and transect surveys. We accounted for potential biases due to
      variation in genetic markers, sample sizes, spatial scales or the level of
      habitat fragmentation. We showed that the various dispersal estimates generally
      converged, and that the relative dispersal ability of species could reliably be
      predicted from their relative vagrancy (records of butterflies outside their
      normal habitat). Expert opinions gave much less reliable estimates of realized
      dispersal but instead reflected migration propensity of butterflies. Within
      species comparisons showed that genetic estimates were relatively invariable,
      while other dispersal estimates were highly variable. This latter point questions
      dispersal as a species-specific, invariant trait.

PMID- 20055816
TI  - Propranolol for complicated infantile haemangiomas: a case series of 30 infants.

PMID- 20055817
TI  - Cutaneous meningioma: extracranial extension from an intracranial tumour.

PMID- 20055818
TI  - Rapid remission of psoriasis with reversible leucopenia after two injections with
      adalimumab.

PMID- 20055819
TI  - Febrile ulceronecrotic Mucha-Habermann disease: a rare dermatological emergency.

PMID- 20055820
TI  - Prevalence of xerosis in patients with coronary heart disease.

PMID- 20055821
TI  - An unusual anatomical colocalization of alopecia areata and vitiligo in a child,
      and improvement during treatment with topical prostaglandin E2.

PMID- 20055822
TI  - A case of juvenile pityriasis rubra pilaris: could varicella be an aetiological
      agent?

PMID- 20055823
TI  - A curious but non-serious local side effect of inhaled iloprost: sudden linear
      erythematous facial rash.

PMID- 20055824
TI  - Squamous cell carcinoma arising from Darier's disease.

PMID- 20055825
TI  - Granuloma annulare resolving with features of mid-dermal elastolysis.

PMID- 20055826
TI  - Repigmentation after epidermal grafting of vitiligo epidermis into normal skin in
      segmental vitiligo.

PMID- 20055827
TI  - T-regulatory cell response in psoriasis and changes with imatinib therapy.

PMID- 20055828
TI  - Childhood generalized pustular psoriasis treated by preprandial ciclosporin
      administration: serum cytokine pattern during the course of the disease.

PMID- 20055829
TI  - The use of cimetidine to reduce dapsone-dependent haematological side-effects in
      a patient with mucous membrane pemphigoid.

PMID- 20055830
TI  - Localized cutaneous amyloid at an insulin injection site.

PMID- 20055831
TI  - Topical tacrolimus may enhance repigmentation with targeted narrowband
      ultraviolet B to treat vitiligo: a randomized, controlled study.

PMID- 20055832
TI  - Cutaneous lymphoid perivascular reaction with atypical CD30+ T cells in a patient
      with multiple myeloma treated with bortezomib.

PMID- 20055833
TI  - Hypoxia-ischaemia is involved in the pathogenesis of vulvar lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease, the
      pathogenesis of which is poorly understood. AIM: To evaluate the role of hypoxia
      ischaemia (HI) in vulvar LS. METHODS: Samples from five patients with vulvar LS
      and five control subjects were collected for analysis by transmission electron
      microscopy (TEM) to reveal the ultrastructural changes of organelles and dermal
      blood capillaries. Samples from 37 patients with vulvar LS and 12 control
      subjects were collected for immunohistochemistry to detect the expression of
      vascular endothelial growth factor (VEGF) and the hypoxia markers hypoxia
      inducible factor (HIF)-1alpha and glucose transporter (Glut)-1. RESULTS: Using
      TEM, the mitochondria of basal cells and vascular endothelial cells in vulvar LS
      tissue were found to be swollen with loss of cristae, and the rough endoplasmic
      reticulum had luminal swelling and ribosomal detachment. Damage to vascular
      endothelial cells, disorganization of capillary architecture and loss of
      capillaries were also seen. By immunohistochemistry, moderate to intense staining
      of VEGF was seen in almost 90% of control sections vs. about 55% of LS sections.
      Glut-1 expression was negative or weak in 75% of control sections vs. moderate to
      very strong in about 80% of vulvar LS sections. Nuclear staining of HIF-1alpha
      was not found in LS or control tissue. CONCLUSIONS: HI is involved in the
      pathogenesis of vulvar LS.

PMID- 20055834
TI  - Diallyl trisulphide-induced apoptosis in human melanoma cells involves
      downregulation of Bcl-2 and Bcl-xL expression and activation of caspases.
AB  - BACKGROUND: Although diallyl trisulphide (DATS) has been found to induce
      apoptosis in various tumour cells, its cytotoxicity in melanoma cells has not yet
      been defined and the molecular pathway by which DATS induces apoptosis is not
      well understood. OBJECTIVES: To determine growth inhibition of DATS in human
      melanoma cells (A375 and M14) by inducing apoptosis, and to investigate the
      mechanism underlying such effects. METHODS: Growth inhibition by DATS was
      estimated by the tetrazolium assay. Apoptosis induction in DATS-treated cells was
      assessed by staining with 4',6-diamidino-2-phenylindole (DAPI) and double
      staining with annexin V and propidium iodide. Expression of Bcl-2, Bax, Bcl
      xL/Bcl-xS, cytochrome c release, activation of caspase-9 and poly(ADP-ribose)
      polymerase (PARP) were determined by western blotting. The activity of caspase-3
      was measured using a colorimetric assay. RESULTS: DATS exerted its cytotoxic
      effect in a time-dependent and dose-dependent manner by inducing apoptosis in
      A375 and M14 cells. Expression of Bcl-2 and Bcl-xL was downregulated. Release of
      cytochrome c and activation of the downstream effectors caspase-3, caspase-9 and
      PARP were detected after DATS sensitization. CONCLUSIONS: DATS inhibits growth of
      melanoma cells by inducing apoptosis in association with downregulation of Bcl-2
      and Bcl-xL and activation of caspases.

PMID- 20055835
TI  - Multifocal lesions of morphoea in a patient with systemic lupus erythematosus.
AB  - A 23-year-old man presented with multiple, brownish, sclerotic patches on his
      forehead and temple, which had first appeared 1 month previously. Six months
      earlier, he had been diagnosed with systemic lupus erythematosus (SLE).
      Histopathological examination showed a pattern consistent with morphoea. We
      report a unique case of SLE and subsequent development of multiple morphoea
      confined to the face.

PMID- 20055836
TI  - Hypergammaglobulinaemic purpura associated with alcoholic liver cirrhosis.
AB  - Hypergammaglobulinaemic purpura (HP) is commonly found in Sjogren's syndrome. We
      report a rare association of HP arising in a patient with alcoholic liver
      cirrhosis. A 65-year-old man presented with palpable purpura on the legs.
      Histological examination of a biopsy taken from the purpura found
      leucocytoclastic vasculitis in the superficial and mid-dermis. The activity of
      the vasculitic skin lesions correlated with liver dysfunction. Increased IgA and
      IgG levels, and hypocomplementaemia, may account for the pathogenesis of the
      hypergammaglobulinaemic immune complex-mediated vasculitis in this case.

PMID- 20055837
TI  - Larval therapy as a palliative treatment for severe arteriosclerotic gangrene on
      the feet.
AB  - Larval therapy (LT) is known to be a gentle and effective method for removing
      necrotic tissue and bacteria and reducing the accompanying unpleasant odour.
      Ischaemia has been considered a relative contraindication for LT. We report a
      patient with ischaemia treated with LT. Inguinal revascularization was performed
      on a 69-year-old man with critical limb ischaemia, diabetes mellitus, heart
      failure and end-stage renal disease. Areas of dry black malodorous gangrene
      remained on the distal areas of the feet after surgery and the patient's poor
      health did not allow any additional surgery. The patient was referred to the
      dermatology department for LT. Although patients are usually given this treatment
      as inpatients, the patient requested treatment at home. After the first LT, there
      was a marked reduction in odour. The gangrene needed repeated applications of
      larvae to remove the dead tissue. After eight treatments, the result was more
      positive than we had expected, with total lack of odour and initiation of
      healing. Larvae cannot penetrate eschar, thus free-range larvae were used because
      they can move beneath the hard necrotic tissue and dissolve it.

PMID- 20055838
TI  - Nasal-type extranodal natural killer/T-cell lymphoma presenting with extensive
      leg ulcers.
AB  - Primary cutaneous T-cell lymphomas are rare and can be difficult to classify
      precisely. We present a case of extranodal natural killer (NK)/T-cell lymphoma in
      a previously healthy, immunocompetent man who presented with extensive necrotic
      leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed
      that the tumour cells were positive for CD3, CD30, granzyme B and T-cell
      intracellular antigen-1, and negative for CD5 and CD56, with positive staining
      for Epstein-Barr virus (EBV) RNA on in situ hybridization. A diagnosis of
      extranodal NK/T-cell lymphoma was made, based on the presence of cytotoxic
      granules and positive EBV RNA staining. The patient was treated with a regimen of
      chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L
      asparaginase and etoposide with initial response.

PMID- 20055839
TI  - Elephantiasis nostras verrucosa in a patient with systemic sclerosis.
AB  - Elephantiasis nostras verrucosa (ENV) is an unusual skin condition characterized
      by dermal fibrosis and hyperkeratotic verrucous lesions resulting from chronic
      nonfilarial lymphoedema. The condition is similar to 'elephantiasis tropica', in
      which elephantiasis develops secondary to filariasis. Lymphatic obstruction can
      be primary or due to various causes such as surgery, tumour, radiation,
      congestive heart failure or obesity. Recurrent attacks of cellulitis lead to
      further impairment of lymphatic drainage, causing permanent swelling, dermal
      fibrosis and epidermal thickening. We report a case of a 56-year-old man with
      systemic sclerosis (SS), who presented with painful lesions on both legs,
      consistent with ENV. He developed extensive, fungating, papillomatous lesions on
      the skin of the legs, toes and dorsa of the feet over a period of 3 years.
      Histology revealed dense dermal fibrosis, oedema of the papillary dermis and
      extensive pseudo-epitheliomatous changes. To our knowledge, this is the first
      report of ENV in which SS was considered to be the primary cause for the
      impairment of lymphatic flow.

PMID- 20055841
TI  - Localized perineal cutaneous nodules: a case of recurrent systemic anaplastic
      large-cell lymphoma.
AB  - We report an unusual case of localized cutaneous nodules heralding the recurrence
      of systemic CD30+ anaplastic large-cell lymphoma (ALCL). A 47-year-old woman
      developed numerous violaceous nodules in the perineal and upper thigh area 3
      years after multimodal treatment and complete remission of primary anaplastic
      large-cell CD30+ lymphoma. Using immunohistochemical and T-cell gene
      rearrangement analysis, a recurrence of her anaplastic large-cell lymphoma was
      diagnosed.

PMID- 20055840
TI  - Acute generalized exanthematous pustulosis induced by itraconazole: an
      immunological approach.
AB  - Acute generalized exanthematous pustulosis (AGEP) is an uncommon disease, which
      presents as a nonfollicular erythematous sterile pustular eruption. More than 90%
      of the cases are induced by adverse drug reactions, often triggered by anti
      infectious systemic drugs. We report a case of itraconazole-induced AGEP in a 22
      year-old man, with an assessment of his cytokine/chemokine production and drug
      specific cell reactivity. We found that AGEP, like other T cell-mediated drug
      eruptions, alters the immunological status of the patient, probably favouring T
      cell activation, recruitment and regulation. Few cases of itraconazole-induced
      AGEP have been described in the literature, and to our knowledge, this is the
      first report in which the cellular immunological features are assessed.

PMID- 20055842
TI  - 18-F fluorodeoxyglucose positron emission tomography indicating unsuspected
      infections in two patients with dermatomyositis.
AB  - Dermatomyositis is an idiopathic inflammatory myopathy that may be associated
      with malignancies. The technique of 18-F fluorodeoxyglucose (FDG)-positron
      emission tomography (PET) is an important tool to investigate underlying
      malignancy in patients with a possible paraneoplastic syndrome. We report two
      consecutive patients with dermatomyositis in whom 18-F FDG-PET revealed
      unsuspected infections. Physicians should be aware that a positive 18-F FDG-PET
      is not specific for malignancy and may reveal other conditions including an
      infectious disorder.

PMID- 20055843
TI  - Onychomycosis caused by Fusarium solani in a woman with diabetes.
AB  - A case of untreated fusarial onychomycosis leading to serious consequences is
      reported. Fusarium solani is a widespread fungus and an occasional human
      pathogen. It usually invades rapidly in immunocompromised hosts, and often
      results in a poor outcome despite treatment. We report a woman with diabetes
      mellitus who had untreated fusarial infection of the nails, which developed into
      subcutaneous fusariosis, superinfected by bacteria, and then evolved into
      osteomyelitis that subsequently resulted in septic shock. Early management of
      mycotic nails in immunocompromised hosts is crucial to prevent life-threatening
      disease.

PMID- 20055844
TI  - Composite haemangioendothelioma with lymph-node metastasis: an unusual
      presentation at an uncommon site.
AB  - A 48-year-old woman presented with red papules on the thigh. Histopathological
      examination indicated pyogenic granuloma, and the patient was treated with total
      excision in 2003 and electrocauterization in 2005. Three months later, upon
      recurrence of the lesions, a diagnosis of composite haemangioendothelioma (CHE)
      was made. The patient was treated by total excision and lymph-node dissection,
      which revealed inguinal lymph-node metastasis. Despite the surgery, a further
      local recurrence occurred, subsequently treated by wide excision en bloc, with
      adjuvant radiotherapy and chemotherapy. Although CHE is defined as a vascular
      tumour with low-grade malignancy, the local recurrences and lymph-node metastases
      resulted in treatment difficulties in this case. Unlike earlier cases, the tumour
      in our patient presented as localized numerous small papulonodules, and lymph
      node metastasis was detected within a relatively short time. Dermatologists and
      pathologists should be aware of this rare condition and include it in the
      differential diagnosis of vascular lesions.

PMID- 20055845
TI  - Epidermolysis bullosa pruriginosa in association with lichen planopilaris.
AB  - Epidermolysis bullosa pruriginosa (EBP) is a clinical variant of dominant or
      occasionally recessive, dystrophic epidermolysis bullosa (EB). Clinically,
      intense pruritus on a background of inherited skin fragility often leads to skin
      signs that resemble acquired inflammatory disorders such as hypertrophic lichen
      planus (LP) or nodular prurigo. Moreover, symptoms and signs may not appear until
      adult life, further compounding difficulties in distinguishing between inherited
      or acquired skin pathology. We describe a 61-year-old white British woman who
      developed EBP during her 40s, with lichenified plaques on the legs that resembled
      hypertrophic LP. Molecular screening of the COL7A1 gene showed a novel
      heterozygous glycine substitution in type VII collagen, designated p.G2290A, in
      keeping with dominant dystrophic EB. During her 50s, however, the patient
      developed new abnormalities with patchy scarring alopecia and perifollicular
      inflammation. Histological examination of a skin biopsy found features of lichen
      planopilaris. To our knowledge, this is the first example of a patient with EBP
      in whom the genetic disease does not merely resemble LP but is actually
      associated with coexisting acquired lichenoid skin pathology. Intriguingly,
      treatment with topical tacrolimus 0.03% led to marked improvement in the
      inflammation on the legs but had little effect on the scalp.

PMID- 20055846
TI  - Successful treatment of lichen amyloidosus associated with atopic dermatitis
      using a combination of narrowband ultraviolet B phototherapy, topical
      corticosteroids and an antihistamine.
AB  - Lichen amyloidosus (LA) is a type of primary localized cutaneous amyloidosis
      characterized by multiple pruritic discrete hyperkeratotic papules with amyloid
      deposition in the papillary dermis. Clinical regression is usually difficult to
      achieve, even after treatment. In this study, we report a case of an adult man
      with LA associated with atopic dermatitis (AD) which was successfully treated
      with narrowband ultraviolet B (NB-UVB) phototherapy, topical corticosteroids and
      an oral antihistamine. This case suggests that NB-UVB phototherapy may be a
      useful adjuvant for LA associated with AD.

PMID- 20055847
TI  - Calcific panniculitis in adult-onset dermatomyositis.
AB  - Dermatomyositis (DM) is an idiopathic inflammatory myopathy associated with
      characteristic cutaneous features. Panniculitis is a rarely reported clinical
      finding in this condition. This report describes two cases of adult-onset DM
      complicated by severe calcific panniculitis. In both cases, the associated pain
      and loss of function seemed to be best managed on combination anti-malarial
      therapy with mepacrine and hydroxychloroquine.

PMID- 20055848
TI  - Subacute cutaneous lupus erythematosus presenting as poikiloderma.
AB  - Subacute cutaneous lupus erythematosus (SCLE) is a recognised variant of lupus
      erythematosus (LE), which accounts for 10-15% of all cases of cutaneous LE,
      occurring most commonly in young to middle-aged white women. Diagnosis is based
      on the detection of anti-Ro/SS-A antibodies in the skin and serum, characteristic
      clinical and histological cutaneous involvement, and relatively mild systemic
      involvement. Several unusual variants of SCLE have been reported including
      erythrodermic SCLE, SCLE with vitiligo-like lesions, acral SCLE and bullous SCLE.
      Poikoilodermatous SCLE is a recognised but rare variant of SCLE. There are
      currently only two case reports, comprising five individual cases, in the
      literature. We present a case of SCLE in which the main clinical findings were an
      extensive photodistributed poikilodermatous rash and alopecia.

PMID- 20055849
TI  - A collection of rare anomalies: multiple digital glomuvenous malformations,
      epidermal naevus, temporal alopecia, heterochromia and abdominal lipoblastoma.
AB  - Glomuvenous malformations are a subtype of venous malformations, which present in
      infancy or childhood. We describe a teenage girl who presented with multiple
      digital glomuvenous malformations from birth. In addition, she had an epidermal
      naevus on the upper lip, an area of congenital alopecia of the scalp,
      heterochromia irides and an abdominal lipoblastoma. We are unaware of any reports
      of the association of multiple glomuvenous malformations with the other uncommon
      developmental anomalies seen in our patient, and a common link eludes us.

PMID- 20055850
TI  - Endogenous ochronosis.
AB  - Endogenous ochronosis or alkaptonuria is a rare, autosomal recessive disease of
      tyrosine metabolism that is caused by a deficiency of the enzyme homogentisic
      acid oxidase. The disease results in the accumulation and deposition of
      homogentisic acid in the cartilage, eyelids, forehead, cheeks, axillae, genital
      region, buccal mucosa, larynx, tympanic membranes, and tendons. The disease
      generally presents in adults with arthritis and skin abnormalities; occasionally,
      involvement of other organs may be seen. A 49-year-old man was referred to our
      clinic with verrucous lesions on his hands. On physical examination, caviar-like
      ochronotic papules were found around his eyes and the helix cartilage of his
      ears, and on the dorsa of both hands. There were brown macules on the sclera
      (Osler's sign). The patient had arthritis and nephrolithiasis, and a sample of
      his urine darkened upon standing. Histopathological examination showed deposition
      of ochronotic pigment. High-dose ascorbic acid was given, and the patient showed
      improvement on follow-up examination 6 months later.

PMID- 20055851
TI  - Focal myositis of the tongue presenting as macroglossia.
AB  - Focal myositis (FM) is a benign localized inflammatory process of unknown
      aetiology, which presents as a rapidly enlarging soft-tissue mass that evolves
      into a localized lesion. It is most often mistaken for a neoplasm.
      Histologically, it is characterized by marked myopathic changes of the muscle
      fibres, lymphocytic infiltration and interstitial fibrosis. We describe a case of
      focal myositis of the tongue and review this rare condition.

PMID- 20055852
TI  - Treatment with carbon dioxide laser of painful skin metastases from a laryngeal
      neuroendocrine carcinoma.
AB  - An 82-year-old man presented with multiple, exquisitely painful skin metastases
      from an atypical carcinoid tumour of the larynx. These were treated successfully
      with carbon dioxide laser. To our knowledge, this is the first reported case of
      laser treatment used in the management of neuroendocrine skin metastases.

PMID- 20055853
TI  - Regular clinical dermatoscope use with training improves melanoma diagnosis by
      dermatologists.
AB  - Dermatoscopy is not accepted by all dermatologists as a useful diagnostic tool.
      We set out to test if training followed by regular clinical use of dermatoscopes
      improved diagnostic accuracy in melanoma diagnosis. Six dermatologists who had
      not previously used dermatoscopes were studied before and after a 10-month period
      of dermatoscope use with training and use of the Modified Pattern Analysis
      Diagnostic Algorithm. Diagnostic accuracy was assessed using test cards
      containing clinical and dermatoscopic photographs. The number of melanomas
      undiagnosed after training fell from 18 to 5 and the number potentially left
      unexcised fell from 18 to 3. The numbers of benign lesions potentially excised
      remained unchanged. The study shows that the use of dermatoscopes with training
      greatly increased the accuracy of diagnosis of melanoma by dermatologists. This
      practical study supports the use of dermatoscopy in pigmented-lesion diagnosis
      and demonstrates how dermatoscopy training could be incorporated into UK
      specialist training programmes.

PMID- 20055854
TI  - Primary cutaneous osteoblastic osteosarcoma: a case report and review of the
      current literature.
AB  - Osteosarcoma is a malignant bone-forming tumour that typically arises within the
      metaphysis of long bones. Extraskeletal osteosarcoma is a rare variant that
      usually arises in the deep soft tissues, especially in the legs. We report a 65
      year-old white man with an ulcerated, nodular lesion of the forearm. Based on the
      histological features and immunohistochemical profile of the tumour, a diagnosis
      of osteoblastic osteosarcoma was made. Osteosarcoma arising in the skin is a rare
      condition that has seldom been reported in the English literature.

PMID- 20055855
TI  - Plasma levels of p53 protein and chromosomal aberrations in patients with
      psoriasis treated with the Goeckerman regimen.
AB  - The Goeckerman regimen (GR) is one of the oldest effective treatments for
      psoriasis. It involves daily dermal application of crude coal tar with dermal
      exposure to ultraviolet (UV) radiation. A study was carried out to evaluate the
      genotoxic risk of GR by comparing p53 protein plasma level and chromosomal
      aberrations (CA) in peripheral lymphocytes in 33 patients with psoriasis, before
      and after GR. Psoriasis Area and Severity Index (PASI) was used to evaluate the
      efficacy of GR. PASI significantly decreased after GR (P < 0.001), confirming the
      excellent efficacy of the treatment, However, significant increases in level of
      p53 protein (P < 0.05) and CA (P < 0.001) after treatment indicates that this
      method carries an increased genotoxic risk in patients with psoriasis.

PMID- 20055856
TI  - Spontaneous resolution of basal cell carcinoma in naevoid basal cell carcinoma
      syndrome/Gorlin's syndrome.
AB  - We describe a 10-year-old patient with naevoid basal cell carcinoma syndrome
      (NBCCS) which was diagnosed when she was 3 years old. She has developed multiple
      basal cell carcinomas (BCCs) over this time, in particular on her face and trunk.
      However, we are interested to report that at least two have resolved
      spontaneously over 2 years without any treatment. This phenomenon has not
      previously been reported and we believe that it could be important for
      understanding lesional biology and for future approaches to management.

PMID- 20055857
TI  - Disseminated rhinosporidiosis with unusual involvement of the nail apparatus.
AB  - Rhinosporidiosis is an uncommon chronic granulomatous disease caused by
      Rhinosporidium seeberi. It primarily affects the nasal mucosa and the
      nasopharynx. The disease may disseminate to the skin, larynx, trachea, genitalia,
      bones and even the internal organs. Although simultaneous onset of nasal and
      disseminated lesions has been reported, dissemination usually occurs several
      years after the onset of nasal lesions. We report a rare case of disseminated
      rhinosporidiosis involving both nares, the nasal mucosa, nasopharynx, oral cavity
      and oropharynx, as well as widespread cutaneous lesions over the trunk and the
      limbs with nail involvement. This last feature has not, to our knowledge, been
      previously reported.

PMID- 20055858
TI  - Spontaneous cure of American cutaneous leishmaniasis due to Leishmania naiffi in
      two Dutch infantry soldiers.
AB  - We report two Dutch infantry soldiers who acquired American cutaneous
      leishmaniasis (ACL) during military jungle training in Surinam. The lesions had
      existed for 3 and 5 months, respectively, before the soldiers presented for
      treatment. The lesions occurred on the head and right thigh, and were small,
      uncomplicated and symptomless. PCR for Leishmania revealed Leishmania naiffi in
      both patients. No treatment was given, and the lesions in both men healed
      spontaneously within 4 and 6 weeks, respectively, after presentation to our
      clinic. CL is one of the important 'tropical' diseases in The Netherlands,
      primarily due to the increasing numbers of cases in travellers and in military
      personnel serving overseas. ACL due to L. naiffi is thought to be a mild
      expression of CL with a self-limiting nature. Lesions seem to be single, mostly
      small, ulcerating and usually appear on the hands, arms and legs. No case of
      mucocutaneous leishmaniasis has yet been attributed to this parasite.

PMID- 20055859
TI  - Extended fungal skin infection due to Aureobasidium pullulans.
AB  - Black yeasts are a rare cause of infections especially in Europe, yet their
      pathological significance is increasing, particularly in cases of
      immunosuppression. We report a 53-year-old immunocompetent woman with an
      extensive skin infection due to Aureobasidium pullulans, who responded well to
      treatment with liposomal amphotericin B.

PMID- 20055860
TI  - Porokeratosis ptychotropica: a lesser-known variant.
AB  - We report a case of the rare porokeratosis variant porokeratosis ptychotropica
      (PP). A circumferential perianal plaque and the characteristic histology of
      multiple cornoid lamellae with underlying dermal amyloid deposition were seen.
      Amyloid deposition was seen in the biopsied intertriginous area of the plaque
      only, which, in concordance with other cutaneous amyloid deposition disorders,
      may suggest a role for friction in the pathogenesis of this histological finding.
      We review the literature on PP and summarize the poor response seen to
      treatments.

PMID- 20055861
TI  - Dermatoscopic features of cutaneous atypical fibroxanthoma: three cases.
AB  - Atypical fibroxanthoma (AFX) is an uncommon, low-grade, malignant, spindle-cell
      tumour of fibrohistiocytic histogenesis, which can mimic other malignant skin
      tumours, such as basal and squamous cell carcinoma (CC), melanoma, and Merkel
      cell carcinoma (MCC). Three cases of AFX were examined by dermatoscopy, which
      revealed white areas and an atypical polymorphous vascular pattern characterized
      by the concurrence of different structures: linear, dotted, hairpin, arborescent
      and highly tortuous vessels, irregularly distributed over the surface.
      Seborrhoeic elements and photoageing may be accompanying features depending on
      the anatomical location of the AFX. AFX may be added to the list of slightly
      pigmented, reddish, malignant cutaneous tumours, such as SCC, MCC,
      amelanotic/hypomelanotic melanoma and eccrine porocarcinoma, which display
      prominent and chaotic dermatoscopic neoangiogenetic features in more advanced
      stages of proliferation.

PMID- 20055862
TI  - A case report and critical appraisal of the literature on the use of DermaSilk in
      children with atopic dermatitis.
AB  - Atopic dermatitis (AD) is easily aggravated by detergents, synthetic and woollen
      clothing, and bacterial colonization. Cotton clothing is often recommended for
      children with AD, but cotton can contain rough fibres that may act as skin
      irritants. In contrast, silk is characterized by smooth fibres with minimal
      potential for irritation. We report a sericin-free silk (DermaSilk), which is
      treated with AEGIS AEM5772/5, a product that has antibacterial properties, and
      evaluate its use in the treatment of AD.

PMID- 20055863
TI  - Non-healing ulcer on the great toe due to cellular schwannoma.
AB  - Cellular schwannoma (CS) occurring in the foot is uncommon, and when it does
      occur, it usually presents as a slowly growing tumour. Ulceration of CS on the
      foot is rare. We report a 20-year-old woman who presented with a painful and non
      healing ulcer on the lateral area of the right great toe, which failed to heal
      despite treatment. Six months after onset of the ulcer, a small swelling appeared
      below it. Histological examination of a biopsy taken from the edge of the ulcer
      established the diagnosis of CS. Preoperative magnetic resonance imaging
      delineated the mass on the lateral area of the right great toe. The mass was
      surgically excised, which led to resolution of the symptoms. This case highlights
      the fact that chronic ulcers in the foot can be due to CS. Correct diagnosis and
      management depend on a histopathological diagnosis.

PMID- 20055864
TI  - Aquagenic syringeal acrokeratoderma in an adult man: case report and review of
      the literature.
AB  - Aquagenic syringeal acrokeratoderma (ASA) is a rare acquired disorder that
      develops predominantly in young women. It is clinically characterized by a
      burning sensation and whitish discolouration on the hands and rarely on the soles
      after brief immersion in water, which resolves within a short time after drying.
      Topical aluminium chloride and salicylic acid are reportedly beneficial in some
      cases. In total, 20 female and 8 male patients with ASA have been reported
      previously. We present another male patient, who failed to respond to treatment
      with antihistamines and topical steroids, but responded well to formalin 3% in
      alcohol without any side-effects.

PMID- 20055865
TI  - Systemic allergic contact dermatitis due to consumption of raw shiitake mushroom.
AB  - Shiitake (Lentinus edodes) is a mushroom that is very popular in Asian cuisine.
      After ingestion of the raw fungus, dermatitis may occur in rare cases, and is
      commonly assumed to be a toxic reaction. We report a 52-year-old man who
      developed a generalized pruritic papulovesicular eruption 2 weeks after daily
      consumption of uncooked shiitake mushrooms. Prick-to-prick and scratch tests with
      uncooked mushrooms resulted in an eczematous reaction at 24 h that peaked at 72 h
      and persisted for 1 week. In contrast, no cutaneous reactions could be elicited
      in 20 healthy people. We conclude that our patient had systemic allergic contact
      dermatitis due to consumption of raw shiitake mushroom.

PMID- 20055866
TI  - Efalizumab-induced thrombocytopenia: report of relapse after re-administration.
AB  - Although a reversible, sometimes severe, drug-induced thrombocytopenia is a
      recognized adverse drug reaction (ADR) in patients with psoriasis treated with
      efalizumab, definite proof for the association of thrombocytopenia with
      efalizumab is still lacking (currently level II evidence for ADR). We report a
      patient with psoriasis who had two episodes of reversible thrombocytopenia during
      efalizumab; the first occurred 5 months after introduction of the medication and
      the second 4 months after re-introduction of efalizumab for relapsing psoriasis.
      The development of a second episode of thrombocytopenia on re-exposure to
      efalizumab provides, for the first time in the literature to our knowledge,
      definite (level I) ADR evidence for efalizumab-induced thrombocytopenia.

PMID- 20055867
TI  - Pityriasis rubra pilaris in association with laryngeal carcinoma.
AB  - Pityriasis rubra pilaris (PRP) is a rare group of hyperkeratotic, papulosquamous
      diseases that can be acquired or inherited. Cases of PRP associated with
      malignancy have been rarely reported. We report a case of 46-year-old man who
      presented with rapidly progressing PRP as a possible initial cutaneous symptom of
      a previously undiagnosed laryngeal carcinoma. Microlaryngoscopy was performed
      because of the patient's hoarseness, and this revealed leucoplakia on the left
      vocal cord. Histopathological examination led to the diagnosis of squamous cell
      carcinoma in situ. After surgical treatment, the clinical signs of PRP began to
      resolve, and the patient was free of skin lesions at follow-up. This case
      represents a rare coexistence of PRP with malignancy, and indicates that PRP can
      occur as paraneoplastic dermatosis associated with laryngeal cancer.

PMID- 20055868
TI  - Patterns of chromonychia during chemotherapy in patients with skin type V and
      outcome after 1 year of follow-up.
AB  - The study was carried out on 17 patients (16 female, 1 male) who presented with
      nail pigmentation after chemotherapy. Ten patients who were given
      cyclophosphamide had diffuse black pigmentation, slate-grey to black longitudinal
      streaks, or diffuse dark-grey pigmentation located proximally with overlying
      black transverse bands. The pigmentation appearing after hydroxyurea was located
      more distally, was brownish-black in colour and diffuse, or appeared in single or
      double transverse bands. Diffuse pigmentation of the skin, patchy macular
      pigmentation of the gum margins, and the tip and lateral margins of the tongue
      were also seen. In patients on carboplatin treatment, brown pigmentation in bands
      2-4 mm wide was seen, located distally on the fingernails. Black longitudinal
      bands on a background of diffuse brown pigmentation were noted after docetaxel
      treatment. Chemotherapy-induced nail pigmentation in patients skin type V is not
      an uncommon event, which is probably underestimated and under-reported.

PMID- 20055869
TI  - Response of extranodal natural killer/T-cell lymphoma, nasal type, to interferon
      alpha, corticosteroid and narrowband ultraviolet B phototherapy.
AB  - Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTLN), is
      characterized by higher prevalence in East Asians and South Americans,
      association with Epstein-Barr virus infection, aggressive nature in most cases,
      and resistance to conventional treatment strategies such as chemotherapy and
      radiotherapy. The optimum treatment for this disease has not yet been
      established. We report a successful treatment experience in a case of ENKTLN,
      with a combination regimen including interferon-alpha, corticosteroid and
      narrowband ultraviolet B, which may serve as a promising therapy for this
      aggressive disease at earlier stages.

PMID- 20055870
TI  - Localized bullous pemphigoid in a patient with primary lymphoedema tarda.
AB  - We report a case of localized bullous pemphigoid (BP) in a woman patient with
      primary lymphoedema tarda. There is only one previous case reported of localized
      pemphigoid in an area of lymphoedema, this being of the cicatricial variant. Slow
      circulation in the lymphatic vessels, increased capillary permeability with
      preferential localization of antibodies in the area, and potential cleavage of
      the epidermal junction due to increased hydrostatic pressure leading to
      autoimmunity, have all been advocated as possible pathogenic mechanisms.
      Nevertheless, we consider that the mechanism by which localized pemphigoid arises
      on lymphoedema remains elusive, based on a previous case of generalized BP
      sparing an area of postsurgical lymphoedema.

PMID- 20055871
TI  - Identification of a U2HR gene mutation in Turkish families with Marie Unna
      hereditary hypotrichosis.
AB  - Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of
      isolated alopecia. The disorder is characterized by the absence or scarcity of
      scalp hair, eyebrows and eyelashes at birth. Coarse wiry hair begins to grow
      during childhood, but this is followed by progressive hair loss, which usually
      begins around puberty. A recent study identified mutations in U2HR, an inhibitory
      upstream open reading frame in the 5'-untranslated region of the human hairless
      gene. We investigated three reportedly unrelated Turkish multigeneration families
      with MUHH. Using direct sequencing of U2HR we were able to identify the c. 2T>A
      (p.M1K) mutation in one index patient of each family. The mutation cosegregates
      perfectly with the disease in all members of the families. To our knowledge, this
      is the first time that a mutation in U2HR has been identified in families from
      the Middle East. The observation of a common mutation is suggestive of a possible
      founder effect.

PMID- 20055872
TI  - One novel and two recurrent mutations in the keratin 5 gene identified in Chinese
      patients with epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is a group of inherited skin diseases,
      characterized by the formation of intraepidermal blisters. We performed genetic
      analysis of the keratin 5 (KRT5) gene in two Chinese pedigrees. One novel
      missense mutation was identified in a patient with sporadic EBS (general, non
      Dowling-Meara). Sequence analysis showed a heterozygous T > A transition at
      nucleotide 1730 of KRT5, changing phenylalanine (Phe) to tyrosine (Tyr) at
      position 577 of the keratin 5 (K5). In addition, two recurrent mutations
      c.1649delG (p.Gly550AlafsX77) and c.508G > (p.Glu170Lys) in KRT5 were identified
      in Chinese patients with mottled pigmentation EBS and localized EBS,
      respectively. None of the mutations were found in any unaffected family members
      or in an additional 100 unrelated control samples. These results suggest that
      these mutations are pathogenic and might be one of the potential causes of EBS in
      these Chinese patients.

PMID- 20055873
TI  - Prognostic relevance of hypoxia inducible factor-1alpha expression in patients
      with melanoma.
AB  - Overexpression of hypoxia inducible factor (HIF)-1alpha has been found in several
      human cancers and is thought to correlate with aggressive disease and poor
      response. A retrospective analysis was carried out on 89 patients with primary
      cutaneous melanoma. HIF-1alpha expression was assessed by immunohistochemistry in
      formalin-fixed, paraffin wax-embedded tumour sections. Overall survival (OS) and
      disease-free survival (DFS) were determined using univariate and multivariate
      analyses. Of the 89 patients, 78 (87.6%) expressed HIF-1alpha, and the remaining
      11 patients (12.4%) did not. HIF-1alpha expression correlated with age (P =
      0.002), but not with the main predictive factors in melanoma. Survival analysis
      disclosed no difference between the groups for OS and DFS. In multivariate
      analysis, only Breslow Index and ulceration were significantly associated with
      poor OS. Our results indicate that HIF-1alpha overexpression is present in most
      primary melanomas, but is not associated with clinicopathological variables,
      patient prognosis or survival.

PMID- 20055874
TI  - Human papillomavirus genome integration in multifocal vulvar Bowen's disease and
      squamous cell carcinoma.
AB  - Human papillomavirus (HPV) is an important aetiological agent in cervical
      carcinomas and in malignant skin tumours. Integration of the HPV DNA into host
      genome is one of the most important risk factors for malignant transformation. We
      report a patient with multiple black plaques and an erythematous nodule on her
      vulva. On histological examination, multifocal vulvar Bowen's disease (BD) and
      invasive squamous cell carcinoma (SCC) were found. An amplification of
      papillomavirus oncogene transcripts (APOT) assay showed that two locations of BD
      had only episome-derived HPV16 transcripts, but the other two sites of BD and the
      nodule of invasive SCC had HPV16 transcripts derived from integration. Sequencing
      analysis revealed that the invasive SCC had its integration site at 8q24, the Myc
      locus. Our results suggest that the APOT assay in multiple sites of the same
      patient may be a valuable tool for evaluation of the clinical degree of
      malignancy for vulvar BD.

PMID- 20055875
TI  - Genetic diagnosis of Hailey-Hailey disease in two Chinese families: novel
      mutations in the ATP2C1 gene.
AB  - Hailey-Hailey disease (HHD; OMIM 169600), is an autosomal dominantly inherited
      disorder characterized by suprabasal cell separation of the epidermis. Mutations
      in ATP2C1, which encodes the human secretory pathway Ca(2+)/ Mn(2) +/- ATPase
      protein 1 (hSPCA1), have been identified as the pathogenic gene of HHD without
      evidence of genetic heterogeneity. In this study, the ATP2C1 gene was screened in
      two typical Chinese pedigrees with HHD, and two specific novel mutations of the
      ATP2CL gene were identified. Family 1 had a 16-base deletion mutation c.1068
      1083del16 and family 2 had a substitution mutation c.1982T>G (p.Met661Arg). DNA
      sequencing of the three descendants of the probands revealed that they all had
      the normal genotype, indicating that there had been no transmission of the
      mutation.

PMID- 20055876
TI  - Refractory epidermolysis bullosa acquisita: successful treatment with rituximab.

PMID- 20055877
TI  - Eosinophilic folliculitis with a Demodex folliculorum infestation successfully
      treated with ivermectin in a man infected with human immunodeficiency virus.

PMID- 20055878
TI  - Oral zinc sulfate for unresponsive cutaneous viral warts: too good to be true? A
      double-blind, randomized, placebo-controlled trial.

PMID- 20055879
TI  - Cardiac masses in a patient with AJCC stage II melanoma: cautious interpretation
      of the magnetic resonance imaging.

PMID- 20055880
TI  - Primary hyperhidrosis controlled with oxybutynin after unsuccessful surgical
      treatment.

PMID- 20055881
TI  - Desmoglein1 and BP 180 ELISA indexes correlating with disease activity in a
      patient with coexisting pemphigus foliaceus and bullous pemphigoid.

PMID- 20055882
TI  - Nutty dermatitis-marking-nut dermatitis after use as a home remedy.

PMID- 20055883
TI  - Extramammary Paget's disease of the penis with features of Bowen's disease.

PMID- 20055884
TI  - A boy with persistent 'atopic eczema' resistant to conventional topical
      therapies.

PMID- 20055885
TI  - An unusual solitary lesion on the glans penis.

PMID- 20055886
TI  - Unusual plaques on the back.

PMID- 20055887
TI  - Multiple asymptomatic skin-coloured papules on the left great and second toes.

PMID- 20055888
TI  - Necrotizing fasciitis due to Cryptococcus neoformans in a diabetic patient with
      chronic renal insufficiency.

PMID- 20055889
TI  - Rapidly involuting congenital haemangioma.

PMID- 20055890
TI  - A localized cutaneous reaction to vitamin K injection in a neonate.

PMID- 20055891
TI  - A ruby (rubor!) anniversary: the Scottish Skin Biology Club 1969-2009.
AB  - The 40th birthday of the Scottish Skin Biology Club (SSBC) was celebrated in
      Spring 2009. The SSBC, formerly The Skin Biology Club, has played a vital role in
      providing a forum and a means of networking for skin researchers in Scotland.
      This paper summarizes the history of the club.

PMID- 20055893
TI  - A vision for the European journal of clinical investigation: note from the new
      editors.

PMID- 20055894
TI  - Lithocholic acid downregulates vitamin D effects in human osteoblasts.
AB  - BACKGROUND: Osteoporosis is a common complication in chronic cholestasis. It has
      been proposed that retained substances such as bile acids may produce a damaging
      effect on bone cells. This study analyses the effects of lithocholic acid (LCA)
      on cell survival and vitamin D metabolism in human osteoblasts (hOB). MATERIALS
      AND METHODS: Human osteoblasts cultures were performed with or without foetal
      bovine serum (FBS) or human albumin (HA) at different LCA concentrations and
      times with or without vitamin D. RESULTS: Lithocholic acid at concentrations
      higher than 10(-5 )M decreased cell survival. This effect was partially prevented
      by the presence of FBS or HA. Vitamin D stimulated CYP24A, BGLAP and TNFSF11
      expression in hOB and these effects were modified by nontoxic LCA concentrations.
      LCA significantly decreased vitamin D stimulation of CYP24A, BGLAP and TNFSF11
      gene expression at 72%, 79% and 56% (respectively). LCA alone has an agonistic
      effect, as has vitamin D, thus partially increasing CYP24A and BGLAP expression,
      but with no changes on TNFRSF11B expression. Equivalent effects of the LCA were
      observed by performing gene reporter assays using MG-63 cells transfected with
      constructs containing CYP24A1 promoter regions. CONCLUSIONS: Lithocholic acid
      decreases the stimulatory effect of vitamin D on CYP24A, BGLAP and TNFSF11
      expression in hOB. This effect is produced through vitamin D response elements
      (VDREs), located in the promoter regions of these genes, suggesting that LCA acts
      as a mild analogous of vitamin D, interacting with the vitamin D receptor. These
      results may explain the potential deleterious effects of retained bile acids on
      hOB.

PMID- 20055895
TI  - A catalogue of reporting guidelines for health research.
AB  - Growing evidence demonstrates widespread deficiencies in the reporting of health
      research studies. The EQUATOR Network is an international initiative that aims to
      enhance the reliability and value of the published health research literature.
      EQUATOR provides resources, education and training to facilitate good research
      reporting and assists in the development, dissemination and implementation of
      robust reporting guidelines. This paper presents a collection of tools and
      guidelines available on the EQUATOR website (http://www.equator-network.org) that
      have been developed to increase the accuracy and transparency of health research
      reporting.

PMID- 20055896
TI  - Genetic risk information for common diseases may indeed be already useful for
      prevention and early detection.

PMID- 20055897
TI  - Personal genomics: information can be harmful.

PMID- 20055898
TI  - Feasibility and challenges of independent research on drugs: the Italian
      medicines agency (AIFA) experience.
AB  - Key points * National Health Service (NHS) is becoming increasingly aware of the
      need to support independent research to answer some important questions for
      patient care in areas of scant commercial interest. * This article reports the
      main features and strategies of the independent research programme on drugs
      launched by the Italian Medicines Agency (AIFA) in 2005. * In the three bids
      launched between 2005 and 2007, a total of 151 studies have been approved for
      funding for a total of about 78 million Euro. * In this article we describe the
      Italian legislative framework under which the programme was launched, the types
      of research funded and discuss how the supported studies could contribute, in an
      international framework, to the knowledge needed on drug efficacy, effectiveness
      and safety.

PMID- 20055899
TI  - Formation and stability of oxygen-rich bubbles that shape photosynthetic mats.
AB  - Gas release in photic-zone microbialites can lead to preservable morphological
      biosignatures. Here, we investigate the formation and stability of oxygen-rich
      bubbles enmeshed by filamentous cyanobacteria. Sub-millimetric and millimetric
      bubbles can be stable for weeks and even months. During this time, lithifying
      organic-rich laminae surrounding the bubbles can preserve the shape of bubbles.
      Cm-scale unstable bubbles support the growth of centimetric tubular towers with
      distinctly laminated mineralized walls. In environments that enable high
      photosynthetic rates, only small stable bubbles will be enclosed by a dense
      microbial mesh, while in deep waters extensive microbial mesh will cover even
      larger photosynthetic bubbles, increasing their preservation potential. Stable
      photosynthetic bubbles may be preserved as sub-millimeter and millimeter-diameter
      features with nearly circular cross-sections in the crests of some Proterozoic
      conical stromatolites, while centrimetric tubes formed around unstable bubbles
      provide a model for the formation of tubular carbonate microbialites that are not
      markedly depleted in (13)C.

PMID- 20055900
TI  - Coupling hydrocarbon degradation to anaerobic respiration and mineral diagenesis:
      theoretical constraints.
AB  - The diagenetic mineral assemblages in petroleum reservoirs control the formation
      fluid pH and pCO(2). Anaerobic biodegradation of petroleum is controlled by the
      transfer of electrons from reduced organic species to inorganic, redox sensitive,
      aqueous and mineral species in many cases through intermediates such as H(2) and
      CH(3)COO(-). The terminal electron accepting reactions induce the dissolution or
      precipitation of the same minerals that control the ambient pH and pCO(2) in
      petroleum reservoirs. In this study, we develop a model for anaerobic
      biodegradation of petroleum that couples the production of acetate and H(2) to
      'late stage' diagenetic reactions. The model reveals that the principal terminal
      electron accepting process and electron donor control the type of diagenetic
      reaction, and that the petroleum biodegradation rate is controlled through
      thermodynamic restriction by the minimum DeltaG required to support a specific
      microbial metabolism, the fluid flux and the mineral assemblage. These
      relationships are illustrated by modeling coupled microbial diagenesis and
      biodegradation of the Gullfaks oil reservoir. The results indicate that the
      complete dissolution of albite by acids generated during oil biodegradation and
      the corresponding elevated pCO(2) seen in the Gullfaks field are best explained
      by methanogenic respiration coupled to hydrocarbon degradation and that the
      biodegradation rate is likely controlled by the pCH(4). Biodegradation of
      Gullfaks oil by a consortium that includes either Fe(3+)-reducing or -reducing
      bacteria cannot explain the observed diagenetic mineral assemblage or pCO(2). For
      octane, biodegradation, not water washing, was the principal agent for removal at
      fluid velocities <20 m Myr(-1).

PMID- 20055901
TI  - Dermatopathology in the age of molecular biology.

PMID- 20055902
TI  - The histological assessment of cutaneous vasculitis.
AB  - Vasculitis is defined as inflammation directed at vessels, which compromises or
      destroys the vessel wall leading to haemorrhagic and/or ischaemic events. Skin
      biopsy is the gold standard for the diagnosis of cutaneous vasculitis, whose
      manifestations include urticaria, infiltrative erythema, petechiae, purpura,
      purpuric papules, haemorrhagic vesicles and bullae, nodules, livedo racemosa,
      deep (punched out) ulcers and digital gangrene. These varied morphologies are a
      direct reflection of size of the vessels and extent of the vascular bed affected,
      ranging from a vasculitis affecting few superficial, small vessels in petechial
      eruptions to extensive pan-dermal small vessel vasculitis in haemorrhagic bullae
      to muscular vessel vasculitis in lower extremity nodules with livedo racemosa.
      Skin biopsy, extending to subcutis and taken from the earliest, most symptomatic,
      reddish or purpuric lesion is crucial for obtaining a high-yielding diagnostic
      sample. Based on histology, vasculitis can be classified on the size of vessels
      affected and the dominant immune cell mediating the inflammation (e.g.
      neutrophilic, granulomatous, lymphocytic, or eosinophilic). Disruption of small
      vessels by inflammatory cells, deposition of fibrin within the lumen and/or
      vessel wall coupled with nuclear debris allows for the confident recognition of
      small vessel, mostly neutrophilic vasculitis (also known as leukocytoclastic
      vasculitis). In contrast, muscular vessel vasculitis can be identified solely by
      infiltration of its wall by inflammatory cells. Extravasation of red blood cells
      (purpura) and necrosis are supportive, but not diagnostic of vasculitis as they
      are also seen in haemorrhagic and/or vaso-occlusive disorders (pseudovasculitis).
      Vasculitic foci associated with extravascular granulomas (palisaded neutrophilic
      and granulomatous dermatitis), tissue eosinophilia, or tissue neutrophilia signal
      the risk for, or co-existence of systemic disease. This essential histological
      information coupled with direct immunofluorescence and anti-neutrophil
      cytoplasmic data and clinical findings enables more precise and accurate
      diagnosis of localized and systemic vasculitis syndromes.

PMID- 20055903
TI  - Histopathology of alopecia: a clinicopathological approach to diagnosis.
AB  - Interpretation of the histopathological findings of primary scarring and non
      scarring alopecias may prove daunting. This is especially true if the biopsy
      specimen is inadequate, and the clinical history and pattern of the alopecia are
      not known. Common forms of scarring alopecias discussed here are the lymphocytic
      (discoid lupus erythematosus, lichen planopilaris, central centrifugal
      cicatricial alopecia, pseudopelade of Brocq), the neutrophilic (folliculitis
      decalvans, dissecting folliculitis), and the mixed (acne keloidalis) entities.
      The non-scarring alopecias reviewed are androgenic alopecia, telogen effluvium,
      alopecia areata, trichotillomania and traction alopecia. In all cases of primary
      alopecia, adequate tissue sampling and appropriate laboratory processing, in
      combination with pertinent clinical information, provide the key to diagnosis.

PMID- 20055904
TI  - Dermatopathological challenges in the human immunodeficiency virus and acquired
      immunodeficiency syndrome era.
AB  - The histopathological assessment of cutaneous lesions is critical to the
      definitive diagnosis of many human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome-associated dermatoses, infections and tumours.
      Dermatopathological challenges stem mainly from the altered histopathological
      profile of established cutaneous entities compared with that in the HIV
      unaffected population, the emergence of new diseases and the impact of
      therapeutic modalities on cutaneous lesions. This review focuses on some of these
      diagnostic dilemmas, with emphasis on the following challenges: (i) infective
      diagnostic pitfalls; (ii) itchy papular skin lesions; (iii) co-lesional comorbid
      diseases; (iv) drug-induced disease alterations; and (v) neoplastic and
      pseudoneoplastic proliferations. The drug-induced alterations include highly
      active antiretroviral therapy-associated disease modifications.

PMID- 20055905
TI  - Classification of cutaneous lymphomas - an update.
AB  - This review focuses on the evolution and conceptual aspects of classifications
      for cutaneous lymphomas. The World Health Organization/European Organization for
      Research and Treatment of Cancer (WHO/EORTC) classification and the WHO
      classification (4th edn, 2008) represent the first widely accepted
      classifications for lymphomas, in which the complete spectrum of primary
      cutaneous lymphomas is included. These classifications for primary cutaneous
      lymphomas define disease entities with distinct clinical, histological,
      immunophenotypic and genetic features. Final diagnosis is based on a synoptic
      integration of these features and implies clinicopathological correlation as a
      pivotal element of the diagnostic approach for primary cutaneous lymphomas. The
      entities, their definitions and diagnostic criteria of cutaneous lymphomas listed
      in the WHO/EORTC and WHO classifications are presented. Recent changes in the
      terminology and staging, practical implications and future perspectives are
      discussed.

PMID- 20055906
TI  - Immunocytochemistry and the diagnosis of cutaneous lymphoma.
AB  - Cutaneous lymphoid infiltrates may pose some of the most difficult diagnostic
      problems in dermatopathology. Immunocytochemistry is often employed in an effort
      to determine whether an infiltrate is neoplastic or, in the case of clearly
      malignant infiltrates, to provide a specific diagnosis. The rarity of these
      disorders and the variant immunocytochemical profiles they may present further
      thwart understanding and sometimes prevent an accurate diagnosis. In this review
      the common immunocytochemical profiles of various cutaneous lymphomas are
      presented and potential pitfalls and problems considered. Immunocytochemistry is
      not a diagnostic test but, as in other areas of histopathology, is a highly
      valuable tool that requires critical interpretation within a context: so applied,
      it is an indispensable part of the pathologist's arsenal in evaluating lymphoid
      infiltrates and defining different lymphomas.

PMID- 20055907
TI  - Blistering skin diseases: a bridge between dermatopathology and molecular
      biology.
AB  - Although dermatopathology and molecular biology are often considered to be
      separate laboratory disciplines, the respective approaches are far from mutually
      exclusive. This is certainly the case for understanding the pathology of
      blistering skin diseases, both acquired and inherited. For example, in toxic
      epidermal necrolysis, dermatopathology in isolation may provide few clues to
      disease pathogenesis. There is widespread keratinocyte apoptosis and a variable
      infiltrate of cytotoxic T cells, but morphology alone offers little insight into
      what causes the epidermal destruction. In contrast, molecular biology studies
      have revealed several key processes that help explain the keratinocyte death,
      including increased expression of death receptors and their ligands on
      keratinocyte cell membranes as well as the presence of local or systemic
      immunocyte-derived cytolytic granules. For some inherited blistering diseases,
      however, such as epidermolysis bullosa, the molecular pathology is complex and
      difficult to unravel in isolation, yet the addition of dermatopathology is
      helpful in focusing molecular investigations. Notably, immunolabelling of cell
      adhesion proteins using specific antibody probes can identify reduced or absent
      immunoreactivity for candidate genes/proteins. Bridging dermatopathology and
      molecular biology investigations facilitates a greater understanding of disease
      processes, improves diagnostic accuracy, and provides a basis for the development
      and appraisal of new treatments.

PMID- 20055908
TI  - Clues to the diagnosis of atypical melanocytic lesions.
AB  - This review, based on a lecture given at the 2009 Update in Dermatopathology
      meeting held at the Institute of Dermatology (London, UK), discusses the problem
      of misdiagnosing atypical benign melanocytic lesions as melanoma and the
      alternative problem of interpreting naevoid melanoma as a banal naevus.
      Consequences are considered. Brief consideration of a range of other melanoma
      variants that may be a source of diagnostic difficulty is also included.

PMID- 20055909
TI  - Dysplastic naevi: an update.
AB  - Dysplastic naevi are clinically atypical and histologically are characterized by
      architectural disorder and cytological atypia. Their diagnosis is reproducible if
      criteria and thresholds are agreed upon. They are significant only in relation to
      melanoma, as simulants of melanoma, as markers of individuals at increased risk
      of developing melanoma, and as potential and occasional actual precursors of
      melanoma. Morphologically and biologically, they are intermediate between common
      naevi and melanoma. Individuals with dysplastic naevi may have deficient DNA
      repair, and dysplastic naevi lesions are associated with overexpression of
      pheomelanin, which may lead to increased oxidative damage and increased potential
      for DNA damage and tumour progression.

PMID- 20055910
TI  - Molecular cytogenetics of cutaneous melanocytic lesions - diagnostic, prognostic
      and therapeutic aspects.
AB  - This review intends to update current knowledge regarding molecular cytogenetics
      in melanocytic tumours with a focus on cutaneous melanocytic lesions. Advantages
      and limitations of diverse, already established methods, such as (fluorescence)
      in situ hybridization and mutation analysis, to detect these cytogenetic
      alterations in melanocytic tumours are described. In addition, the potential
      value of more novel techniques such as multiplex ligation-dependent probe
      amplification is pointed out. This review demonstrates that at present
      cytogenetics has mainly increased our understanding of the pathogenesis of
      melanocytic tumours, with an important role for activation of the mitogen
      activated protein kinase (MAPK) signalling pathway in the initiation of
      melanocytic tumours. Mutations in BRAF (in common naevocellular naevi), NRAS
      (congenital naevi), HRAS (Spitz naevi) and GNAQ (blue naevi) can all cause MAPK
      activation. All these mutations seem early events in the development of
      melanocytic tumours, but by themselves are insufficient to cause progression
      towards melanoma. Additional molecular alterations are implicated in progression
      towards melanoma, with different genetic alterations in melanomas at different
      sites and with varying levels of sun exposure. This genetic heterogeneity in
      distinct types of naevi and melanomas can be used for the development of
      molecular tests for diagnostic purposes. However, at the moment only few
      molecular tests have become of diagnostic value and are performed in daily
      routine practice. This is caused by lack of large prospective studies on the
      diagnostic value of molecular tests including follow-up, and by the low
      prevalence of certain molecular alterations. For the future we foresee an
      increasing role for cytogenetics in the treatment of melanoma patients with the
      increasing availability of targeted therapy. Potential targets for metastatic
      melanoma include genes involved in the MAPK pathway, such as BRAF and RAS. More
      recently, KIT has emerged as a potential target in melanoma patients. These
      targeted treatments all need careful evaluation, but might be a promising adjunct
      for treatment of metastatic melanoma patients, in which other therapies have not
      brought important survival advantages yet.

PMID- 20055912
TI  - Cutaneous fibrohistiocytic tumours - an update.
AB  - The term 'fibrohistiocytic' tumour is a descriptive designation without
      histogenetic connotation for a group of heterogeneous lesions that share
      morphological features of histiocytes and fibroblasts on light microscopy.
      However, over the years it has become apparent that many so-called
      'fibrohistiocytic' tumours are largely composed of relatively undifferentiated
      mesenchymal cells, but can also show areas of myofibroblastic differentiation.
      This review focuses on the clinical and histological features as well as
      differential diagnosis of so-called fibrohistiocytic tumours. Special emphasis is
      given to more recently described histological variants of fibrous histiocytoma,
      e.g. cellular, epithelioid, aneurysmal and atypical fibrous histiocytoma, to
      angiomatous and plexiform fibrous histocytoma (plexiform fibrohistiocytic
      tumour), lesions that are not true variants of fibrous histiocytomas but have
      erroneously been designated such, and to atypical fibroxanthoma. The literature
      on metastasizing fibrous histiocytoma is also reviewed.

PMID- 20055913
TI  - A new method of imaging particle tracks in solid state nuclear track detectors.
AB  - Solid state nuclear track detectors are used to determine the concentration of
      alpha particles in the environment. The standard method for assessing exposed
      detectors involves 2D image analysis. However 3D imaging has the potential to
      provide additional information relating to angle as well as to differentiate
      clustered hit sequences and possibly energy of alpha particles but this could be
      time consuming. Here we describe a new method for rapid high-resolution 3D
      imaging of solid state nuclear track detectors. A 'LEXT' OLS3100 confocal laser
      scanning microscope (Olympus Corporation, Tokyo, Japan) was used in confocal mode
      to successfully obtain 3D image data on four CR-39 plastic detectors. Three
      dimensional visualization and image analysis enabled characterization of track
      features. This method may provide a means of rapid and detailed 3D analysis of
      solid state nuclear track detectors.

PMID- 20055911
TI  - Sebaceous neoplasia and the Muir-Torre syndrome: important connections with
      clinical implications.
AB  - Sebaceous neoplasia comprises a spectrum ranging from benign to malignant. Proper
      histological identification is important for treatment, prognosis and potential
      association with the Muir-Torre syndrome (MTS). Our increased understanding of
      the significance and pathogenesis of these tumours has led to improved risk
      stratification, screening recommendations, and treatment of patients with an
      initial presentation of a sebaceous tumour. This review focuses on the diagnostic
      and histological features of sebaceous lesions, the MTS, and recent insights into
      the molecular pathogenesis of sebaceous tumours.

PMID- 20055914
TI  - Controlled dehydration of a biological sample using an alternative form of
      environmental SEM.
AB  - In this study a non-conductive biological sample is observed free of charging
      artefacts when placed on a cooled Peltier stage in the specimen chamber of an
      alternative form of the environmental scanning electron microscope, equipped with
      a specially designed hydration system. This system was used to create dynamically
      changing surrounding conditions leading to controlled dehydration of the sample
      enabling us to visualize the topographical structure of a rat tongue in the
      transition region between the liquid and the gas state of water in the microscope
      specimen chamber.

PMID- 20055915
TI  - Real-time computation of subdiffraction-resolution fluorescence images.
AB  - In the recent past, single-molecule based localization or photoswitching
      microscopy methods such as stochastic optical reconstruction microscopy (STORM)
      or photoactivated localization microscopy (PALM) have been successfully
      implemented for subdiffraction-resolution fluorescence imaging. However, the
      computational effort needed to localize numerous fluorophores is tremendous,
      causing long data processing times and thereby limiting the applicability of the
      technique. Here we present a new computational scheme for data processing
      consisting of noise reduction, detection of likely fluorophore positions, high
      precision fluorophore localization and subsequent visualization of found
      fluorophore positions in a super-resolution image. We present and benchmark
      different algorithms for noise reduction and demonstrate the use of non-maximum
      suppression to quickly find likely fluorophore positions in high depth and very
      noisy images. The algorithm is evaluated and compared in terms of speed, accuracy
      and robustness by means of simulated data. On real biological samples, we find
      that real-time data processing is possible and that super-resolution imaging with
      organic fluorophores of cellular structures with approximately 20 nm optical
      resolution can be completed in less than 10 s.

PMID- 20055916
TI  - Comparison of different methods for thin section EM analysis of Mycobacterium
      smegmatis.
AB  - Bacteria are generally difficult specimens to prepare for conventional resin
      section electron microscopy and mycobacteria, with their thick and complex cell
      envelope layers being especially prone to artefacts. Here we made a systematic
      comparison of different methods for preparing Mycobacterium smegmatis for thin
      section electron microscopy analysis. These methods were: (1) conventional
      preparation by fixatives and epoxy resins at ambient temperature. (2) Tokuyasu
      cryo-section of chemically fixed bacteria. (3) rapid freezing followed by freeze
      substitution and embedding in epoxy resin at room temperature or (4) combined
      with Lowicryl HM20 embedding and ultraviolet (UV) polymerization at low
      temperature and (5) CEMOVIS, or cryo electron microscopy of vitreous sections.
      The best preservation of bacteria was obtained with the cryo electron microscopy
      of vitreous sections method, as expected, especially with respect to the
      preservation of the cell envelope and lipid bodies. By comparison with cryo
      electron microscopy of vitreous sections both the conventional and Tokuyasu
      methods produced different, undesirable artefacts. The two different types of
      freeze-substitution protocols showed variable preservation of the cell envelope
      but gave acceptable preservation of the cytoplasm, but not lipid bodies, and
      bacterial DNA. In conclusion although cryo electron microscopy of vitreous
      sections must be considered the 'gold standard' among sectioning methods for
      electron microscopy, because it avoids solvents and stains, the use of optimally
      prepared freeze substitution also offers some advantages for ultrastructural
      analysis of bacteria.

PMID- 20055917
TI  - Image correlation microscopy for uniform illumination.
AB  - Image cross-correlation microscopy is a technique that quantifies the motion of
      fluorescent features in an image by measuring the temporal autocorrelation
      function decay in a time-lapse image sequence. Image cross-correlation microscopy
      has traditionally employed laser-scanning microscopes because the technique
      emerged as an extension of laser-based fluorescence correlation spectroscopy. In
      this work, we show that image correlation can also be used to measure
      fluorescence dynamics in uniform illumination or wide-field imaging systems and
      we call our new approach uniform illumination image correlation microscopy. Wide
      field microscopy is not only a simpler, less expensive imaging modality, but it
      offers the capability of greater temporal resolution over laser-scanning systems.
      In traditional laser-scanning image cross-correlation microscopy, lateral
      mobility is calculated from the temporal de-correlation of an image, where the
      characteristic length is the illuminating laser beam width. In wide-field
      microscopy, the diffusion length is defined by the feature size using the spatial
      autocorrelation function. Correlation function decay in time occurs as an object
      diffuses from its original position. We show that theoretical and simulated
      comparisons between Gaussian and uniform features indicate the temporal
      autocorrelation function depends strongly on particle size and not particle
      shape. In this report, we establish the relationships between the spatial
      autocorrelation function feature size, temporal autocorrelation function
      characteristic time and the diffusion coefficient for uniform illumination image
      correlation microscopy using analytical, Monte Carlo and experimental validation
      with particle tracking algorithms. Additionally, we demonstrate uniform
      illumination image correlation microscopy analysis of adhesion molecule domain
      aggregation and diffusion on the surface of human neutrophils.

PMID- 20055918
TI  - Time-lapse FRET microscopy using fluorescence anisotropy.
AB  - We present recent data on dynamic imaging of Rac1 activity in live T-cells.
      Forster resonance energy transfer between enhanced green and monomeric red
      fluorescent protein pairs which form part of a biosensor molecule provides a
      metric of this activity. Microscopy is performed using a multi-functional high
      content screening instrument using fluorescence anisotropy to provide a means of
      monitoring protein-protein activity with high temporal resolution. Specifically,
      the response of T-cells upon interaction of a cell surface receptor with an
      antibody coated multi-well chamber was measured. We observed dynamic changes in
      the activity of the biosensor molecules with a time resolution that is difficult
      to achieve with traditional methodologies for observing Forster resonance energy
      transfer (fluorescence lifetime imaging using single photon counting or frequency
      domain techniques) and without spectral corrections that are normally required
      for intensity based methodologies.

PMID- 20055919
TI  - Time-lapse imaging of in vitro myogenesis using atomic force microscopy.
AB  - Myoblast therapy relies on the integration of skeletal muscle stem cells into
      distinct muscular compartments for the prevention of clinical conditions such as
      heart failure, or bladder dysfunction. Understanding the fundamentals of
      myogenesis is hence crucial for the success of these potential medical therapies.
      In this report, we followed the rearrangement of the surface membrane structure
      and the actin cytoskeletal organization in C2C12 myoblasts at different stages of
      myogenesis using atomic force microscopy (AFM) and confocal laser scanning
      microscopy (CLSM). AFM imaging of living myoblasts undergoing fusion unveiled
      that within minutes of making cell-cell contact, membrane tubules appear that
      unite the myoblasts and increase in girth as fusion proceeds. CLSM identified
      these membrane tubules as built on scaffolds of actin filaments that nucleate at
      points of contact between fusing myoblasts. In contrast, similarly behaving
      membrane tubules are absent during cytokinesis. The results from our study in
      combination with recent findings in literature further expand the understanding
      of the biochemical and membrane structural rearrangements involved in the two
      fundamental cellular processes of division and fusion.

PMID- 20055920
TI  - Model based precision structural measurements on barely resolved objects.
AB  - A model based method for the accurate quantification of the 3D structure of
      fluorescently labelled cellular objects similar in size to the optical resolution
      limit is presented. This method is applied to both simulated confocal images of
      chromatin structures and to real confocal data obtained on a Fluorescence in situ
      Hybridization (FISH) labelled gene domain. The model assumes that the object is
      composed of a small number of discrete points which are convolved with the
      microscope point spread function to give the image. Fitting this model to image
      data results in a method to assess object structure which is accurate, shows a
      low bias, and does not require user intervention or the potentially subjective
      setting of a threshold.

PMID- 20055921
TI  - Cryofixation rapidly preserves cytoskeletal arrays of leaf epidermal cells
      revealing microtubule co-alignments between neighbouring cells and adjacent actin
      and microtubule bundles in the cortex.
AB  - Accurate preservation of microtubule and actin microfilament arrays is crucial
      for investigating their roles in plant cell development. Aldehyde fixatives such
      as paraformaldehyde or glutaraldehyde preserve cortical microtubule arrays but,
      unless actin microfilaments are stabilized with drugs such as m-maleimidobenzoyl
      N-hydroxysuccinimide ester (MBS), ethylene glycol bis[sulfosuccinimidylsuccinate]
      (sulfo-EGS) or phalloidin, their arrays are often poorly preserved. Cryofixation,
      used primarily for electron microscopy, preserves actin microfilaments well but
      is used rarely to fix plant cells for optical microscopy. We developed a novel
      whole-mount cryofixation method to preserve microtubule and microfilament arrays
      within Tradescantia virginiana leaf epidermal cells for investigation using
      confocal microscopy. Cortical microtubule arrays were often oriented in different
      directions on the internal and external faces of the epidermal cells. A number of
      arrays were aligned in several directions, parallel to microtubules of
      neighbouring cells. Actin microfilaments were particularly well preserved
      possibly due to the speed with which they were immobilized. No transverse
      cortical microfilament arrays were observed. On occasion, we observed co-aligned
      microfilament and microtubule bundles lying adjacent to the plasma membrane and
      positioned side by side suggesting a potential direct interaction between the
      cytoskeletal filaments at these locations. Cryofixation is therefore a valuable
      tool to investigate the interactions between cytoskeletal arrays in plant cells
      using confocal microscopy.

PMID- 20055922
TI  - Observation of three-dimensional internal structure of steel materials by means
      of serial sectioning with ultrasonic elliptical vibration cutting.
AB  - A three-dimensional (3D) internal structure observation system based on serial
      sectioning was developed from an ultrasonic elliptical vibration cutting device
      and an optical microscope combined with a high-precision positioning device. For
      bearing steel samples, the cutting device created mirrored surfaces suitable for
      optical metallography, even for long-cutting distances during serial sectioning
      of these ferrous materials. Serial sectioning progressed automatically by means
      of numerical control. The system was used to observe inclusions in steel
      materials on a scale of several tens of micrometers. Three specimens containing
      inclusions were prepared from bearing steels. These inclusions could be detected
      as two-dimensional (2D) sectional images with resolution better than 1 mum. A
      three-dimensional (3D) model of each inclusion was reconstructed from the 2D
      serial images. The microscopic 3D models had sharp edges and complicated
      surfaces.

PMID- 20055923
TI  - Automated detection of tuberculosis in Ziehl-Neelsen-stained sputum smears using
      two one-class classifiers.
AB  - Screening for tuberculosis in high-prevalence countries relies on sputum smear
      microscopy. We present a method for the automated identification of Mycobacterium
      tuberculosis in images of Ziehl-Neelsen-stained sputum smears obtained using a
      bright-field microscope. We use two stages of classification. The first comprises
      a one-class pixel classifier for object segmentation. Geometric transformation
      invariant features are extracted for implementation of the second stage, namely
      one-class object classification. Different classifiers are compared; the
      sensitivity of all tested classifiers is above 90% for the identification of a
      single bacillus object using all extracted features. The mixture of Gaussians
      classifier performed well in both stages of classification. This method may be
      used as a step in the automation of tuberculosis screening, in order to reduce
      technician involvement in the process.

PMID- 20055924
TI  - Full spectrum filterless fluorescence microscopy.
AB  - In conventional microscopes, fluorescence emission is separated from the
      backscattered illumination using the Stokes shift, whereby the emission occurs at
      a longer wavelength to the excitation. Such separation is usually achieved
      through a combination of wavelength filters that divide the spectrum into
      mutually exclusive excitation and emission bands. It is therefore impossible in
      these microscopes to access the full excitation/emission spectrum of the specimen
      in a single image. We report on a microscope that acquired fluorescence images
      using illumination across the spectral range 450-680 nm; the full emission
      spectrum was detected simultaneously across the same range. The microscope was
      also combined with structured illumination optical sectioning to give three
      dimensionally resolved images with improved background rejection. Full spectrum
      fluorescence images of biological specimens are demonstrated. As this system is
      more versatile than the standard fluorescence microscope, it could be of benefit
      in many fluorescence imaging applications.

PMID- 20055926
TI  - Premastication.

PMID- 20055927
TI  - Commentaries on Premastication: the second arm of infant and young child feeding
      for health and survival? By Gretel Pelto, Yuanyuan Zhang & Jean-Pierre Habicht.

PMID- 20055928
TI  - Difference in ponderal growth and body composition among pregnant vs. never
      pregnant adolescents varies by birth outcomes.
AB  - Recently, we showed that following pregnancy and 6 months of lactation,
      adolescents cease linear growth and have reduced fat and lean mass in rural
      Bangladesh. Here, we examined whether these changes varied by pregnancy outcomes
      such as fetal loss, low birthweight (LBW) and neonatal mortality. Anthropometric
      measurements were taken among 12-19-year-old primigravidae (n = 229) in early
      pregnancy and at 6 months post-partum. Never-pregnant adolescents (n = 456)
      matched on age and time since menarche were also measured at the same time.
      Change in anthropometry among pregnant vs. never-pregnant adolescents was
      compared by pregnancy outcome adjusting for confounders using mixed effects
      regression models. Pregnant girls, irrespective of birth outcome, did not gain in
      stature, while never-pregnant girls increased in height by 0.36 +/- 0.04 cm year(
      1) (P < 0.05). Body mass index, mid-upper arm circumference (MUAC) and % body fat
      among pregnant adolescents whose infants survived the neonatal period had
      decreased at 6 months post-partum, whereas those who experienced a fetal loss or
      neonatal death did not change in any of the measurements. Consequently, the
      difference in change in ponderal size and body composition measures between
      pregnant and never-pregnant girls was higher among those whose neonates survived
      vs. those who experienced a fetal loss/neonatal death (BMI: -0.64 +/- 0.11 vs.
      0.01 +/- 0.16 kg m(-2) year(-1); MUAC: -0.96 +/- 0.12 vs. -0.35 +/- 0.17 cm year(
      1), both P < 0.05). LBW and preterm birth did not have a similar effect
      modification. Linear growth ceased among pregnant girls regardless of birth
      outcome. Maternal weight loss and depletion of fat and lean mass at 6 months post
      partum were more pronounced when the infants survived through the neonatal
      period.

PMID- 20055929
TI  - Inappropriate bottle use: an early risk for overweight? Literature review and
      pilot data for a bottle-weaning trial.
AB  - Identifying early risk factors for childhood obesity is critical, as weight in
      infancy and early childhood tracks to later periods. Continued bottle use -
      primarily from excess milk intake - is emerging as a potential risk factor for
      early childhood overweight. Over three fourths of US infants drink from bottles
      beyond the recommended weaning age of 12 months, and two thirds of UK infants use
      a bottle at 18 months. This paper is divided into three parts. Part 1 reviews the
      literature on beverage intake, weight and bottle use in young children. Part II
      describes pilot data on milk bottle use and weight in 12-60-month-olds, collected
      prior to a randomized controlled (RCT) trial of a bottle-weaning intervention.
      Median daily milk bottle consumption at 12 months was 5.0 (interquartile range =
      3-6). Among 12-36-month-olds, current users were significantly more likely to be
      >95th% weight-for-height (19% vs. 0%, P < 0.02), and more were >85% weight-for
      height (27% vs. 11%, P < 0.11), vs. non-users. In contrast, current bottle use
      was not associated with either overweight or obesity in 37-60-month-olds. Part
      III describes the RCT, begun in fall 2008. It is enrolling 464 parent/12-month
      old dyads from a nutrition assistance programme for low-income families.
      Children's bottle use, anthropometrics, dietary intake and nutrient density (via
      24 h recall) are assessed quarterly through 24 months of age. For the
      intervention, site nutritionists employ a project-developed, visually attractive
      flip chart. An observational study nested within the RCT will describe dietary
      changes during this period of feeding transitions.

PMID- 20055930
TI  - Establishing individual peer counselling for exclusive breastfeeding in Uganda:
      implications for scaling-up.
AB  - Exclusive breastfeeding remains critical for child survival, potentially reducing
      childhood morbidity and mortality. In Uganda, 98% of children are ever breastfed,
      but exclusive breastfeeding levels remain low. Supporting mothers in
      breastfeeding exclusively can improve breastfeeding practices. This paper
      describes experiences of establishing individual peer counselling for exclusive
      breastfeeding in the Uganda site of the Promoting Infant Health and Nutrition in
      Sub-Saharan Africa: Safety and Efficacy of Exclusive Breastfeeding Promotion in
      the Era of HIV trial, and highlights some implications for scaling-up. Twelve
      women were identified by their communities, one from each of 12 clusters. They
      were trained for 6 days and followed up for 1 year while they counselled mothers.
      Their knowledge and attitudes towards exclusive breastfeeding were assessed
      before and immediately after training, and also 10 months into peer counselling.
      Observations, field notes and records of interactions with peer counsellors were
      used to record experiences from this intervention. The communities were receptive
      to peer counselling and women participated willingly. After training and 10
      months' follow-up, their knowledge and attitude to exclusive breastfeeding
      improved. All were retained in the study, and mothers accepted them in their
      homes. They checked for mothers several times if they missed them on the first
      attempt. Husbands and grandmothers played key roles in infant feeding decisions.
      Involving the communities in selection helped to identify reliable breastfeeding
      peer counsellors who were acceptable to mothers and were retained in the study.
      Other key issues to consider for scaling-up such interventions include training
      and follow up of peer counsellors, which led to improved knowledge and attitudes
      towards exclusive breastfeeding (ClinicalTrials.gov no: NCT00397150).

PMID- 20055931
TI  - Understanding infant feeding beliefs, practices and preferred nutrition education
      and health provider approaches: an exploratory study with Somali mothers in the
      USA.
AB  - The objective of this study was to explore Somali mothers' beliefs and practices
      around infant feeding and education, towards developing a culturally informed
      infant nutrition curriculum for health providers. Four focus groups were
      conducted to explore: (1) beliefs about infant feeding, hunger and ideal weight;
      (2) feeding practices; (3) nutrition education approaches; and (4)
      provider/mother interactions. Thirty-seven Somali mother participants identified
      the following themes within these topics: (1) strategies for assessing hunger,
      satiety and when to feed; shared beliefs that plump babies are healthy, leading
      to worry about infant weight; (2) context of breast milk adequacy, difficulties
      breastfeeding and environmental and cultural barriers to breastfeeding, leading
      to nearly universal early supplementation with formula; (3) preferred education
      approaches include provider visits with interpreters, Somali language educational
      materials and advice from older, experienced family members; and (4) desired
      health provider skills include: listening, explaining, empathy, addressing
      specific concerns, repeating important information, offering preventive advice
      and sufficient visit time. This study presents knowledge about Somali beliefs and
      practices that can directly guide discussions with these families. Given that
      these infants appear on a trajectory towards obesity, influencing infant feeding
      practices in the Somali community is a good upstream approach to preventing
      obesity. These findings will underpin a new infant nutrition curriculum for
      health providers.

PMID- 20055932
TI  - Quality of care in nutritional rehabilitation in HIV-endemic Malawi: caregiver
      perspectives.
AB  - In Malawi, HIV and malnutrition are two of the most common causes of childhood
      morbidity and mortality. This qualitative study based in Nutrition Rehabilitation
      Units (NRU) in HIV-endemic Malawi explores caregiver's (staff and family)
      perspectives on quality of care for severely malnourished children. Three carer
      focus groups and 30 carer and staff in-depth interviews were conducted in two
      NRUs. The interviews and data analysis used a grounded theory approach, using
      both male and female Malawian researchers. Trustworthiness was enhanced through
      the researchers' prolonged engagement with the study setting and participants.
      The use of multiple methods - interviews, focus groups and observation - allowed
      for triangulation of the data. Data was then cross-referenced between staff and
      family caregiver reports. The analysis generated five themes. 'We have different
      blood' referring to staff attitudes and underperformance, 'What wrong did I do to
      God?' referring to stigma and chronic illness, 'My other children back home'
      referring to the carer's multiple responsibilities and challenges, 'Always in
      short supply' referring to resources available in the NRU (milk, medicine, space,
      hygiene) and 'you are always lagging behind' referring to the need for change and
      participants recommendations. Quality of care is a complex issue, bound by
      resources and capacity, influenced by stigma and hierarchy and limited by
      caregivers' conflicting responsibilities. Valuing and involving caregivers is
      essential in improving quality of care. Care should be patient and family centred
      and HIV services should be integrated into malnutrition care at the hospital and
      community level.

PMID- 20055936
TI  - Use of lipid-based nutrient supplements (LNS) to improve the nutrient adequacy of
      general food distribution rations for vulnerable sub-groups in emergency
      settings.
AB  - The term 'lipid-based nutrient supplements' (LNS) refers generically to a range
      of fortified, lipid-based products, including products like Ready-to-Use
      Therapeutic Foods (RUTF) (a large daily ration with relatively low micronutrient
      concentration) as well as highly concentrated supplements (1-4 teaspoons/day,
      providing <100 kcal/day) to be used for 'point-of-use' fortification. RUTF have
      been successfully used for the management of severe acute malnutrition (SAM)
      among children in emergency settings. Recent research on smaller doses of LNS for
      prevention of malnutrition has created interest in their potential use in
      emergency settings to ensure a more nutritionally adequate ration for the most
      vulnerable groups [e.g. infants and children between 6 and 24 months of age, and
      pregnant and lactating women (PLW)]. Currently, the main food and nutrition
      interventions in emergency settings include general food distribution (GFD)
      rations, which are provided to the affected population as a whole, and selective
      (or supplementary) feeding programs (SFP), which are to be provided to
      nutritionally vulnerable or malnourished individuals. In addition to logistical
      and operational challenges that may limit the intended effect of these programs,
      the nutritional quality of the food commodities provided may be insufficient to
      meet the needs of infants and young children and PLW. Because these subgroups
      have particularly high nutrient needs for growth and development, meeting these
      needs is challenging in settings where the ration is limited to a few food
      commodities, with little access to a diverse diet and bioavailable sources of
      micronutrients. In recent years, there has been increased attention to adding
      micronutrient interventions, on top of the other food-based interventions (such
      as GFDs and SFPs), to fill micronutrient gaps in diets in emergency settings. The
      focus of this document is the potential role of LNS in meeting the nutritional
      needs of these vulnerable subgroups, with the goal of preventing malnutrition in
      emergency-affected populations. The document addresses the desired nutritional
      formulation of LNS for these target groups, taking into account the expected
      bioavailability of relevant nutrients and toxicity concerns. It also discusses
      the recommended chemical forms of the fortificants in LNS; stability and shelf
      life considerations; production, packaging and distribution of LNS in the context
      of emergencies; and cost implications of the addition of LNS to current GFD
      rations for vulnerable groups. To develop the desired nutritional formulation of
      LNS for these purposes, we calculated the current nutrient content of commonly
      provided GFD rations and determined the nutritional 'gaps' (of both micro- and
      macronutrients) of these rations for each of the target groups (i.e. children 6
      35 months of age and PLW). For fat and protein, both quantity and quality were
      evaluated. Through an iterative process, we determined the formulation of a small
      dose of LNS that would best meet the recommended nutrient intakes for each group
      in combination with other foods in the GFD ration [composed of a grain, pulse,
      oil, sugar and salt, but excluding a fortified blended food (FBF)], as well as
      breast milk for children 6-24 months of age, while avoiding excess levels of any
      one nutrient to the extent possible. The composition of the LNS used for these
      calculations is based on an existing LNS product (Nutributter, Malaunay, France,
      Nutriset), but with less sugar and more oil. Two different approaches were used:
      (1) developing two different formulations of LNS, one to be used for infants and
      children 6-35 months of age and a separate one for PLW; and (2) developing a
      single formulation that could be used for all of these subgroups. We used
      commodity cost data to estimate the cost of adding an LNS product to the GFD
      ration. The results indicate that the typical GFD ration currently provided in
      emergency settings--based on cereals, pulse, an FBF such as corn-soy blend (CSB),
      oil, salt and sugar-does not meet the nutritional needs of infants and young
      children and PLW. The hypothetical intake from a ration composed of food aid
      commodities (based on the current USAID/USDA specifications for exported food aid
      commodities used in emergency settings), and including breast milk for children 6
      24 months of age, provided less than 75% of the recommended intake for several
      micronutrients for certain age/physiologic groups, including calcium, iron, zinc,
      B vitamins such as riboflavin, B6 and B12, and fat-soluble vitamins such as D, E
      and K. It also generally contained lower than recommended levels of fat and
      essential fatty acids. The initial LNS formulation for each target group was
      designed to provide 100% of the recommended amount (RDA or RNI) for most
      micronutrients per daily dose (20 g, approximately 118 kcal) of LNS. This would
      ensure consumption of the recommended levels of each nutrient even if the 'base'
      diet changed. However, because such a formulation could provide excess amounts of
      certain nutrients when consumed in combination with the 'base' diet (especially
      when the 'base' diet contains fortified foods), we made adjustments in the LNS
      formulation when there was a risk of greatly exceeding the Upper Level for
      certain subgroups and there were relevant concerns about adverse effects from
      chronic consumption of such amounts. For most nutrients, consumption of toxic
      amounts is highly unlikely with the proposed LNS formulations. The 'one-size' LNS
      formulation was designed so that one 'dose' (20 g) would be provided to infants
      and young children and two 'doses' (i.e. 40 g/day) would be provided to PLW. This
      'one-size' formulation was based on the LNS formulation developed for children 6
      35 months of age. Although the resulting formulation is not a perfect match for
      the unique nutritional needs of each subgroup, there are several practical
      advantages to using such an approach. As anticipated, addition of LNS to the GFD
      ration, even after eliminating the FBF (e.g. CSB), increases the cost. The
      'revised' ration without CSB but with LNS would cost 34-52% more (food only) than
      the 'typical' GFD diet for a hypothetical mother-infant pair, depending on how
      many LNS 'doses' were provided to the mother. However, depending on the
      contribution of food costs to overall program costs, the overall increase in
      costs may be significantly less. Although cost is an important consideration,
      options to improve the nutritional quality of foods provided in emergency
      settings should also be assessed with regard to effectiveness in maintaining and
      improving nutritional outcomes. Another consideration is whether a specialized
      product like LNS is more easily targeted to the individuals for whom it is
      intended, thus reducing inter- and intra-household sharing, a common concern with
      other fortified products such as CSB. This could have substantial cost
      implications because programs usually compensate for sharing by inflating the
      amount of FBF provided. This document is intended to be a starting point for
      considering the incorporation of LNS in the food packages provided in emergency
      settings. Our goal was to examine the potential nutritional benefits but also the
      challenges of adopting such a strategy. There are many different options for
      emergency nutrition programs, and there are also many considerations governing
      which option to choose. This document is intended to encourage further evaluation
      of all of these options.

PMID- 20055937
TI  - Non-opsonic phagocytosis of homologous non-toxigenic and toxigenic
      Corynebacterium diphtheriae strains by human U-937 macrophages.
AB  - As interactions between bacteria and macrophages dictate the outcome of most
      infectious diseases, analyses of molecular mechanisms of non-opsonic phagocytosis
      should lead to new approaches for the prevention of diphtheria and systemic
      Corynebacterium diphtheriae infections. The present study aimed to evaluate human
      macrophage-bacteria interactions in the absence of opsonin antibodies and the
      influence of the tox gene on this process. Homologous C. diphtheriae tox+ and tox
      strains were evaluated for adhesion, entering and survival within U-937 human
      macrophages at different incubation periods. Higher numbers of viable bacteria
      associated with and internalized by macrophages were demonstrated for the tox+
      strain. However, viable intracellular bacteria were detected at T-24 hr only for
      the tox- strain. Cytoskeletal inhibitors, cytochalasin E, genistein and
      colchicine, inhibited intracellular viability of both strains at different
      levels. Bacterial replication was evidenced at T-24 hr in supernatants of
      monolayers infected with the tox- strain. Host cell death and nuclear alterations
      were evidenced by the Trypan blue exclusion assay and DAPI fluorescence
      microscopy. ELISA of histone-associated DNA fragments allowed detection of
      apoptosis and necrosis induced by tox+ and tox- strains at T-1 hr and T-3 hr. In
      conclusion, human macrophages in the absence of opsonins may not be promptly
      effective at killing diphtheria bacilli. The presence of the tox gene influences
      the susceptibility of C. diphtheriae to human macrophages and the outcome of non
      opsonic phagocytosis. C. diphtheriae strains exhibit strategies to survive within
      macrophages and to exert apoptosis and necrosis in human phagocytic cells,
      independent of the tox gene.

PMID- 20055938
TI  - Broad-spectrum antiviral effect of Agrimonia pilosa extract on influenza viruses.
AB  - Influenza virus continues to emerge and re-emerge, posing new threats for humans.
      Here we tested various Korean medicinal plant extracts for potential antiviral
      activity against influenza viruses. Among them, an extract of Agrimonia pilosa
      was shown to be highly effective against all three subtypes of human influenza
      viruses including H1N1 and H3N2 influenza A subtypes and influenza B virus. The
      EC(50) value against influenza A virus, as tested by the plaque reduction assay
      on MDCK cells, was 14-23 microg/ml. The extract also exhibited a virucidal effect
      at a concentration of 160-570 ng/ml against influenza A and B viruses when the
      viruses were treated with the extract prior to plaque assay. In addition, when
      tested in embryonated chicken eggs the extract exhibited a strong inhibitory
      effect in ovo on the H9N2 avian influenza virus at a concentration of 280 ng/ml.
      Quantitative RT-PCR analysis data showed that the extract, to some degree,
      suppressed viral RNA synthesis in MDCK cells. HI and inhibition of neuraminidase
      were observed only at high concentrations of the extract. And yet, the extract's
      antiviral activity required direct contact between it and the virus, suggesting
      that its antiviral action is mediated by the viral membrane, but does not involve
      the two major surface antigens, HA and NA, of the virus. The broad-spectrum
      antiviral activity of Agrimonia pilosa extract on various subtypes of influenza
      viruses merits further investigation as it may provide a means of managing avian
      influenza infections in poultry farms and potential avian-human transmission.

PMID- 20055939
TI  - Non-structural and nucleocapsid proteins of Punta Toro virus induce apoptosis of
      hepatocytes through both intrinsic and extrinsic pathways.
AB  - Punta Toro virus (PTV; family Bunyaviridae, genus Phlebovirus) causes severe
      hepatic damage through brisk apoptosis of hepatocytes. In the present study, two
      viral proteins encoded by the S segment of the viral genome, non-structural (NSs)
      and nucleocapsid protein (N), were examined for their roles in apoptosis.
      Expression of NSs in HepG2 cells led to apoptosis in 45% of transfected cells,
      and with N, 28%, on average. These levels represent a four- to an eightfold
      increase over cells transfected with the mutated protein vectors. Caspase-3, -8
      and -9 activities were increased by N protein when compared with the control NC
      (P < 0.05), and by NSsA and NSsB, as compared to control NSsC (P < 0.01).
      Treatment of the transfected cells with caspase-8 or -9 inhibitors markedly
      decreased apoptosis. Neutralization of TNF-alpha or Fas ligand had no effect on
      apoptosis. These results indicate that both NSs and N are responsible for causing
      hepatocyte apoptosis by triggering the extrinsic caspase-8 and intrinsic caspase
      9 pathways.

PMID- 20055940
TI  - Effect of the extract made from Cochinchina momordica seeds on the humoral immune
      responses of mice to a commercial foot-and-mouth disease vaccine (serotypes O and
      Asia 1).
AB  - The extract from ECMS was investigated for its effect on the humoral immune
      responses to foot-and-mouth disease vaccination. Fifty-six mice were randomly
      divided into seven groups with eight animals in each. Mice in groups 5 to 7 were
      subcutaneously (s.c.) injected with 0.5 mg DEX daily for 4 days to induce
      immunosuppression. The animals were then orally given ECMS (200 microg in 250
      microl saline) in groups 3 and 6 or 250 microl saline in group 2, or s.c.
      injected with ECMS (50 microg in 100 microl saline) in groups 4 and 7 or 100
      microl saline in group 5. After that, the animals in groups 2 to 7 were s.c.
      immunized twice with 100 microl of commercial oil-adjuvanted bivalent FMDV
      vaccine (serotypes O and Asia 1) at intervals of 21 days. Mice in group 1
      received injection of 100 microl saline only. After 2 weeks, blood was sampled to
      determine FMDV-specific IgG and isotype IgG1, IgG2a, IgG2b and IgG3. Results
      indicated that oral administration or s.c. injection of ECMS augmented responses
      of specific IgG and most IgG isotypes. Giving ECMS tended to enhance serum
      specific IgG and IgG isotype responses of mice immunosuppressed by s.c. injection
      of DEX. Considering the safety and immunomodulatory effect of ECMS in both normal
      and immunosuppressed mice demonstrated in the present study, this extract
      deserves further investigation to evaluate its potential in improving FMD
      vaccination in farm animals such as pigs, sheep and cattle.

PMID- 20055941
TI  - T cell activation in abnormal perinatal events.
AB  - The aim of this study was to determine the percentage of CD45RO(+) T cells in
      umbilical cord blood from neonates born at less than 37 weeks of gestation. Fifty
      nine patients were enrolled in this study, including 49 with preterm and 10 with
      term deliveries. Preterm deliveries were divided into two categories; spontaneous
      (Group A, n= 31) and indicated (Group B, n= 18). Perinatal infection was
      categorized as C-CAM, H-CAM and neonatal infection. The percentage of CD45RO(+) T
      cells in the umbilical cord was assessed using flow cytometry. IL-6 was measured
      using ELISA. In Group A, the percentage of CD45RO(+) T cells and concentrations
      of IL-6 in patients with perinatal infection (n= 18) were significantly higher
      than in those without perinatal infection (n= 13). A significant correlation
      between percentage of CD45RO(+) T cells and IL-6 concentrations was observed in
      the cord blood (r= 0.62, P= 0.001). In Group B, pink-tinged amniotic fluid was
      observed in seven cases. In these cases, an increase in the percentage of
      CD45RO(+) T cells (>10%) was noted. In the cases without perinatal infection,
      which included all those delivered at term (n= 32), no correlation was observed
      between the percentage of CD45RO(+) T cells and gestational age at delivery (r=
      0.139, P= 0.448). We concluded that a high percentage of CD45RO(+) cord blood T
      cells is observed not only in perinatal infection, but also in the presence of
      abnormal perinatal events such as maternal bleeding in preterm gestation.

PMID- 20055942
TI  - Mycobacterium paraterrae sp. nov. recovered from a clinical specimen: novel
      chromogenic slow growing mycobacteria related to Mycobacterium terrae complex.
AB  - A previously unidentified, slowly growing scotochromogenic Mycobacterium was
      isolated from a Korean patient with symptomatic pulmonary infection.
      Phenotypically, this strain was generally similar to Mycobacterium terrae complex
      strains, however it uniquely produced orange pigmentation. Unique mycolic acid
      profiles and phylogenetic analyses based on three alternative chronometer
      molecules, 16S rRNA gene, hsp65 and rpoB, confirmed the taxonomic status of this
      strain as a novel species. These results support that this strain represents a
      novel Mycobacterium species. The name Mycobacterium paraterrae sp. nov. is
      proposed. The type strain is 05-2522 (= DSM 45127 = KCTC 19556).

PMID- 20055943
TI  - Bifidobacterium suppresses IgE-mediated degranulation of rat basophilic leukemia
      (RBL-2H3) cells.
AB  - Sixteen heat-killed bifidobacteria isolated from human intestine and a probiotic
      strain Lactobacillus GG were tested for their ability to influence IgE-mediated
      degranulation of rat basophilic leukemia (RBL-2H3) cells in vitro. The
      bifidobacteria suppressed IgE-mediated degranulation of RBL-2H3 cells by 1.6
      56.4% in a strain-dependent manner. Bifidobacteria from healthy infants expressed
      high inhibitory effects on IgE-mediated degranulation (41-55%), while those from
      allergic infants varied greatly in their effects against degranulation.
      Bifidobacteria taxonomically identified as Bifidobacterium bifidum exhibited much
      stronger inhibitory effects against IgE-mediated degranulation than those
      taxonomically identified as B. adolescentis (P < 0.05).These results indicate
      that the intestinal bifidobacteria might be one of factors influencing IgE
      mediated allergic responses.

PMID- 20055944
TI  - Possible circulation of H5N1 avian influenza viruses in healthy ducks on farms in
      northern Vietnam.
AB  - To estimate the prevalence of influenza A subtype H5N1 viruses among domestic
      ducks in the period between October and November 2006 when H5N1 outbreaks had
      been absent, 1106 healthy ducks raised in northern Vietnam were collected.
      Inoculation of all throat and cloacae samples into embryonated eggs resulted in
      the isolation of subtype H3N8 in 13 ducks, but not H5N1 viruses. Serological
      analyses demonstrated that five ducks (0.45%) solely developed H5N1 subtype
      specific hemagglutinin-inhibiting and neuraminidase-inhibiting antibodies
      together with anti-non-structural protein 1 antibodies. The results suggested
      that the ducks were naturally infected with H5N1 viruses when obvious H5N1
      outbreaks were absent.

PMID- 20055945
TI  - Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification
      system.
AB  - The classification and grading of papillary urothelial neoplasms has been a long
      standing subject of controversy. Previously, numerous diverse grading schemes for
      bladder tumor, including the 1973 World Health Organization (WHO) classification,
      existed whereby one of the major limitations was poor inter-observer
      reproducibility among pathologists. The WHO/International Society of Urological
      Pathology (ISUP) consensus classification system of urothelial neoplasms of the
      urinary bladder was developed in 1998 and was revised most recently in 2003
      (published in 2004). Importantly, the current classification system provides
      detailed histological criteria for papillary urothelial lesions and allows for
      designation of a lesion (papillary urothelial neoplasm of low malignant
      potential) with a negligible risk of progression. Thus, the latest system is
      designed to be a universally acceptable one for bladder tumors that not only
      could be effectively used by pathologists, urologists, and oncologists, but also
      stratifies the tumors into prognostically significant categories. This article
      outlines the 2004 WHO/ISUP classification system regarding the specific
      histological criteria for non-invasive papillary urothelial neoplasms and the
      clinical significance of each category.

PMID- 20055946
TI  - Chromosomal abnormalities of clear cell renal cell carcinoma: frequent gain of
      chromosome 7.
AB  - Gain of chromosome 7 is well known to be a characteristic abnormality of
      papillary renal cell carcinoma (RCC). The purpose of the present study was to
      perform cytogenetic analysis of G-band karyotype in 16 clear cell RCC obtained
      from nephrectomy. The age of patients ranged from 50 to 79 years and the tumor
      size in largest dimension ranged from 1.8 to 6.2 cm. As a result, the structural
      abnormality of chromosome 3 was most frequently observed (eight clones). Loss of
      chromosome 3 and gain of chromosome 7 followed (four clones). Among four clones
      showing gain of chromosome 7, two were associated with the abnormality of
      chromosome 3 and the remaining two were devoid of the abnormalities of chromosome
      3. In addition, none of all four tumors showing gain of chromosome 7 demonstrated
      any foci of papillary growth pattern. The present study shows that gain of
      chromosome 7 is not exclusive to papillary RCC, but it can be found in clear cell
      RCC as well, and this finding may represent a diagnostic pitfall in
      distinguishing clear cell RCC from papillary RCC.

PMID- 20055947
TI  - Epithelial-mesenchymal transition in human lungs with usual interstitial
      pneumonia: quantitative immunohistochemistry.
AB  - Fibroblastic foci, a major histological feature of usual interstitial pneumonia
      (UIP), play a critical role in the development of UIP. The mechanisms involved in
      the formation of these foci, however, including cellular origin, remain unclear.
      Recent in vitro and animal studies suggested epithelial-mesenchymal transition
      (EMT) of alveolar epithelial cells during pulmonary fibrogenesis. The aim of the
      present study was to investigate the presence of EMT in patients with UIP on
      quantitative immunohistochemistry using pathological tissue sections. The study
      subjects were 13 patients with UIP pattern among 52 patients with interstitial
      pneumonia who underwent lung biopsy. Alveolar epithelial cells overlying
      fibroblastic foci expressed epithelial markers less frequently and mesenchymal
      markers more frequently compared with those in non-diseased control lung tissues
      (n= 10). Moreover, double immunostaining showed that some epithelial cells
      stained for both epithelial and mesenchymal markers. Furthermore, significantly
      higher numbers of epithelial marker-positive fibroblastic cells were found in
      fibroblastic foci in UIP as well as in other non-UIP fibrosing diseases than in
      control lung tissues. The results showed that some epithelial cells overlying
      fibroblastic foci lose the epithelial phenotype and gain the mesenchymal
      phenotype, and that some fibroblastic cells in fibroblastic foci originate from
      epithelial cells. But this EMT may not be specific for UIP.

PMID- 20055948
TI  - Clinicocytopathology of breast cancers with a ring-like appearance on
      ultrasonography and/or magnetic resonance imaging.
AB  - On breast cancer imaging some cancers have an anechoic or high-echoic zone in the
      tumor on ultrasonography and ring-shaped enhancement on contrast-enhanced
      magnetic resonance imaging (MRI) with high intensity in the central area of the
      tumor on T2-weighted imaging, necessitating their differentiation from benign
      disease. Thus, nine breast cancers with a ring-like appearance on imaging were
      analyzed on cytopathology. Histologically the cancer cells of these lesions
      showing a ring-like appearance were located in the periphery of the tumor, with a
      central hypocellular zone. Five such lesions with a thick, doughnut-like
      appearance were identified as cancers with acellular zones (CAC), and four
      lesions with a thinner, rim-like appearance as matrix-producing carcinomas (MPC).
      The percentage ratio of the cancer-zone width to the tumor diameter was 26.4 +/-
      7.8 and 8.0 +/- 3.2 (mean +/- SD), respectively (P= 0.003). Cytologically, highly
      atypical, naked-nucleus cells were observed in eight of the nine cancers. In two
      MPC and three CAC, cartilage matrix and amorphous material, respectively, were
      observed in the background. In summary, the present series of breast cancers
      having a ring appearance on imaging did not have uniform cytopathological
      features. They were classified as MPC or CAC, and cytology was useful in their
      diagnosis and differentiation in some cases.

PMID- 20055949
TI  - Macrophages in Langerhans cell histiocytosis are differentiated toward M2
      phenotype: their possible involvement in pathological processes.
AB  - Although numerous macrophages are found in the lesions of Langerhans cell
      histiocytosis (LCH), their activation phenotypes and their roles in the disease
      process have not been clarified. Paraffin-embedded LCH samples were examined on
      immunohistochemistry and it was found that CD163 can be used to distinguish
      infiltrated macrophages from neoplastic Langerhans cells (LC). The number of
      CD163-positve macrophages was positively correlated with the number of
      multinucleated giant cells (MGC), indicating that most MGC are derived from
      infiltrated macrophages. A significant number of CD163-positive macrophages were
      positive for interleukin (IL)-10 and phospho-signal transducer and activator of
      transcription-3 (pSTAT3), an IL-10-induced signal transduction molecule. This
      indicates that these macrophages are polarized to anti-inflammatory macrophages
      of M2 phenotype. Tumor-derived macrophage-colony-stimulating factor (M-CSF) was
      considered to responsible for inducing M2 differentiation of infiltrated
      macrophages. The number of CD163-positive macrophages in different cases of LCH
      varied, and interestingly the density of CD163-positive macrophages was inversely
      correlated with the Ki-67-positivity of LC. Although the underlying mechanism is
      not fully elucidated, macrophage-derived IL-10 was considered to be involved in
      the suppression of tumor cell proliferation via activation of STAT3.

PMID- 20055950
TI  - Extrarenal teratoid Wilms' tumor: two cases in unusual locations, one associated
      with elevated serum AFP.
AB  - Teratoid Wilms' tumor is an unusual morphological entity characterized by a
      classic triphasic malignancy with predominantly heterologous tissue. The authors
      describe two cases of teratoid Wilms' tumor with an extrarenal site: one in a 13
      year-old girl with vaginal spotting (patient 1) and another in a 1-day-old girl
      with a sacrococcygeal mass (patient 2). The tumors were located in the vagina and
      coccyx, respectively. Under the initial clinical diagnosis of sarcoma botryoides
      in patient 1 and teratoma in patient 2, the masses were removed. Microscopically,
      both tumors were composed of typical triphasic Wilms' tumor tissue with primitive
      cartilage and skeletal muscle, and squamous and columnar mucinous epithelia. The
      patient with sacrococcygeal mass (patient 2) had an elevated serum AFP level. The
      patients were given chemotherapy and have now remained disease free for 7 years 1
      month, and 2 years 5 months after surgery, respectively. Familiarity with this
      rare variant of Wilms' tumor might be important in arriving at a correct
      diagnosis.

PMID- 20055951
TI  - Minimal deviation mucinous adenocarcinoma ('adenoma malignum') of the uterine
      corpus.
AB  - Primary mucinous adenocarcinomas of the uterine corpus are typically low grade
      and frequently associated with endometrial hyperplasia and/or ordinary
      endometrioid adenocarcinoma, but may appear as a heterogeneous group of
      neoplasms. A case is described of a 56-year-old postmenopausal woman who
      presented with mucinous vaginal discharge. Imaging demonstrated thickened
      myometrium due to adenomyosis. Serum CA19-9 levels were elevated to 486 U/mL.
      Microscopic examination of hysterectomy specimens indicated highly differentiated
      mucinous adenocarcinoma diffusely infiltrating the portion of adenomyosis of the
      corpus. In some areas endometrial glands of adenomyosis were replaced by benign
      looking mucinous metaplasia. The uterine cervix showed no abnormalities. HIK1083
      and MUC6 immunohistochemistry indicated a gastric phenotype of the tumor, as seen
      in cases of prototypical minimal deviation adenocarcinoma (MDA) of the cervix. In
      summary, mucinous endometrial adenocarcinoma rarely shows features similar to MDA
      of the cervix. This case provokes a discussion on diagnostic and management
      strategy, and histogenesis of mucinous neoplasm of the endometrium.

PMID- 20055952
TI  - Intraductal oncocytic papillary carcinoma of the pancreas showing numerous
      hyaline globules in the lumen.
AB  - Two cases of intraductal oncocytic papillary carcinoma (IOPC) treated surgically
      were analyzed on light microscopy and immunohistochemistry: that of a 61-year-old
      man and that of a 55-year-old man. There were no clinical symptoms in either
      case. Pancreatic abnormalities were discovered incidentally on CT. Various
      clinical examinations were carried out, and the preoperative diagnosis was
      intraductal papillary mucinous carcinoma (IPMC) in both cases. Surgery was
      performed. Macroscopic observation of tissue cross-sections indicated
      multilocular cystic mass containing polypoid lesions encapsulated by the dilated
      pancreatic duct. Histologically, the cyst walls were lined by columnar epithelial
      cells with complex papillary projections associated with oxyphilic cytoplasm, and
      they were strongly immunoreactive with anti-mitochondrial antibody in the
      cytoplasm. Electron microscopy showed numerous mitochondria in the cytoplasm.
      IOPC was diagnosed. Interestingly, amorphous hyaline globules were produced from
      the oxyphilic cells, which exhibited a bud-like appearance. The hyaline globules
      were not positive for mucin staining. No case of IPMC with hyaline globules has
      been reported to date. The production of hyaline globules may be related to
      oncocytic differentiation. It is suggested that hyaline globules should be
      regarded as a characteristic of IOPC.

PMID- 20055953
TI  - Concurrent xanthogranulomatous orchiepididymitis and seminoma in the same testis.
AB  - Xanthogranulomatous orchiepididymitis (XGO) is a rare inflammatory and
      destructive disease of the testis that may simulate testicular malignancy. To the
      authors' knowledge only 19 cases of XGO have been previously reported. Herein is
      reported the case of a 52-year-old man with XGO who presented with a left
      testicular mass and pyogenic discharge from the scrotum. Ultrasound examination
      indicated heterogeneous testicular areas suggestive of neoplasia. Testicular
      tumor markers were normal. Orchidectomy was performed and histopathology showed
      XGO and a concurrent, occult typical seminoma. As far as the authors know the
      coincidence of these two lesions has not been documented previously. XGO may
      mimic testicular malignancy and may coexist with it. Pathologists should be aware
      of this concurrence of lesions to avoid potential misdiagnosis. Wide sampling of
      the orchidectomy specimens with XGO is mandatory to exclude an occult seminoma.

PMID- 20055954
TI  - Pancreatic undifferentiated carcinoma with osteoclast-like giant cells
      masquerading as (extra)gastrointestinal stromal tumor: potential diagnostic
      pitfall.

PMID- 20055955
TI  - Meningothelial-like whorls in a retroperitoneal cellular schwannoma: potential
      diagnostic pitfall.

PMID- 20055957
TI  - Expression quantitative trait loci analysis in plants.
AB  - An expression Quantitative Trait Locus or eQTL is a chromosomal region that
      accounts for a proportion of the variation in abundance of a mRNA transcript
      observed between individuals in a genetic mapping population. A single gene can
      have one or multiple eQTLs. Large scale mRNA profiling technologies advanced
      genome-wide eQTL mapping in a diverse range of organisms allowing thousands of
      eQTLs to be detected in a single experiment. When combined with classical or
      trait QTLs, correlation analyses can directly suggest candidates for genes
      underlying these traits. Furthermore, eQTL mapping data enables genetic
      regulatory networks to be modelled and potentially provide a better understanding
      of the underlying phenotypic variation. The mRNA profiling data sets can also be
      used to infer the chromosomal positions of thousands of genes, an outcome that is
      particularly valuable for species with unsequenced genomes where the chromosomal
      location of the majority of genes remains unknown. In this review we focus on
      eQTL studies in plants, addressing conceptual and technical aspects that include
      experimental design, genetic polymorphism prediction and candidate gene
      identification.

PMID- 20055958
TI  - Monoterpene engineering in a woody plant Eucalyptus camaldulensis using a
      limonene synthase cDNA.
AB  - Metabolic engineering aimed at monoterpene production has become an intensive
      research topic in recent years, although most studies have been limited to herbal
      plants including model plants such as Arabidopsis. The genus Eucalyptus includes
      commercially important woody plants in terms of essential oil production and the
      pulp industry. This study attempted to modify the production of monoterpenes,
      which are major components of Eucalyptus essential oil, by introducing two
      expression constructs containing Perilla frutescens limonene synthase (PFLS)
      cDNA, whose gene products were designed to be localized in either the plastid or
      cytosol, into Eucalyptus camaldulensis. The expression of the plastid-type and
      cytosol-type PFLS cDNA in transgenic E. camaldulensis was confirmed by real-time
      polymerase chain reaction (PCR). Gas chromatography with a flame ionization
      detector analyses of leaf extracts revealed that the plastidic and cytosolic
      expression of PFLS yielded 2.6- and 4.5-times more limonene than that accumulated
      in wild-type E. camaldulensis, respectively, while the ectopic expression of PFLS
      had only a small effect on the emission of limonene from the leaves of E.
      camaldulensis. Surprisingly, the high level of PFLS in Eucalyptus was accompanied
      by a synergistic increase in the production of 1,8-cineole and alpha-pinene, two
      major components of Eucalyptus monoterpenes. This genetic engineering of
      monoterpenes demonstrated a new potential for molecular breeding in woody plants.

PMID- 20055959
TI  - Genetically pyramiding protease-inhibitor genes for dual broad-spectrum
      resistance against insect and phytopathogens in transgenic tobacco.
AB  - Protease inhibitors provide a promising means of engineering plant resistance
      against attack by insects and pathogens. Sporamin (trypsin inhibitor) from sweet
      potato and CeCPI (phytocystatin) from taro were stacked in a binary vector, using
      pMSPOA (a modified sporamin promoter) to drive both genes. Transgenic tobacco
      lines of T0 and T1 generation with varied inhibitory activity against trypsin and
      papain showed resistance to both insects and phytopathogens. Larvae of
      Helicoverpa armigera that ingested tobacco leaves either died or showed delayed
      growth and development relative to control larvae. Transgenic tobacco
      overexpressing the stacked genes also exhibited strong resistance against
      bacterial soft rot disease caused by Erwinia carotovora and damping-off disease
      caused by Pythium aphanidermatum. Thus, stacking protease-inhibitor genes, driven
      by the wound and pathogen responsive pMSPOA promoter, is an effective strategy
      for engineering crops to resistance against insects and phytopathogens.

PMID- 20055960
TI  - Expression of pigeonpea hybrid-proline-rich protein encoding gene (CcHyPRP) in
      yeast and Arabidopsis affords multiple abiotic stress tolerance.
AB  - A hybrid-proline-rich protein encoding gene (CcHyPRP) has been isolated and
      characterized, for the first time, from the subtracted cDNA library of pigeonpea
      (Cajanus cajan L.) plants subjected to drought stress. Functionality of CcHyPRP
      has been validated for abiotic stress tolerance using the heterologous yeast and
      Arabidopsis systems. The CcHyPRP contained a repetitive proline-rich (PR) N
      terminal domain and a conserved eight cysteine motif (8CM) at the C-terminus.
      Southern analysis disclosed single-copy nature of CcHyPRP gene in the pigeonpea
      genome. Northern analysis revealed higher levels of CcHyPRP transcripts in PEG,
      NaCl, heat (42 degrees C), cold and ABA-treated plants compared with the weak
      signals observed in the untreated plants, suggesting stress-responsive nature of
      the CcHyPRP gene. In yeast, expression of CcHyPRP imparted marked tolerance
      against abiotic stresses exerted by PEG, high temperature, NaCl and LiCl.
      Transgenic Arabidopsis lines, expressing CcHyPRP under the control of CaMV35S and
      rd29A promoters, when subjected to PEG, mannitol, NaCl, LiCl and heat (42 degrees
      C) stress, developed into healthy plants with profuse root system and increased
      biomass in contrast to the weak-stunted wild-type plants. The CcHyPRP-transgenics
      driven by stress-inducible rd29A exhibited similar stress-tolerance as that of
      CaMV35S-lines without any negative effects on plant morphology, implying that
      stress-inducible promoters are preferable for production of stress tolerant
      transgenics. The overall results amply demonstrate the profound effect of CcHyPRP
      in bestowing multiple abiotic stress tolerance at cellular and whole plant
      levels. Accordingly, the multipotent CcHyPRP seems promising as a prime candidate
      gene to fortify crop plants with abiotic stress tolerance.

PMID- 20055961
TI  - Carbon monoxide improves adaptation of Arabidopsis to iron deficiency.
AB  - Carbon monoxide (CO) is an endogenous gaseous molecule and regulates a variety of
      biological processes in animals. However, whether CO regulates nutrient stress
      responses in plants is largely unknown. In this paper, we described an
      observation that CO can regulate iron-homeostasis in iron-starved Arabidopsis.
      Exogenous CO at 50 microm was able to prevent the iron deficient-induced
      chlorosis and improve chlorophyll accumulation. Expression of AtIRT1, AtFRO2,
      AtFIT1 and AtFER1 was up-regulated by CO exposure in iron-deficient seedlings. CO
      regulated iron homeostasis could also be found in monocot maize and green alga
      Chlamydomonas reinhardtii. Treatment with external CO increased iron accumulation
      in iron-deficient Arabidopsis and C. reinhardtii, and restored leaf greening in
      Maize ys1 and ys3 mutants (defective in Fe uptake). Moreover, endogenous CO level
      was increased in Arabidopsis under iron-deficiency. Finally, CO exposure induced
      NO accumulation in root tips. However, such an action could be blocked by NO
      scavenger cPTIO. These results indicate that CO may play an important role in
      improving plant adaptation to iron deficiency or cross-talking with NO under the
      iron deficiency.

PMID- 20055962
TI  - Hope, ethics, and action for sustainable change.

PMID- 20055963
TI  - Health and safety needs in early care and education programs: what do directors,
      child health records, and national standards tell us?
AB  - OBJECTIVE: To identify the overlapping and unique health and safety needs and
      concerns identified by early care and education (ECE) directors, health records,
      and observed compliance with national health and safety (NHS) standards. DESIGN
      AND SAMPLE: Cross-sectional study. 127 ECE programs from 5 California counties
      participated in the study, including 118 directors and 2,498 children's health
      records. MEASURES: Qualitative data were collected using standardized ECE
      directors' interviews to identify their health and safety concerns; and
      objective, quantitative data were collected using child health record reviews to
      assess regular health care, immunizations, health insurance, special health care
      needs, and screening tests and an observation Checklist of 66 key NHS standards
      collected by research assistants. RESULTS: The overlapping health and safety
      needs and concerns identified by the directors and through observations were
      hygiene and handwashing, sanitation and disinfection, supervision, and the safety
      of indoor and outdoor equipment. Some of the health and safety needs identified
      by only one assessment method were health and safety staff training, medical
      plans for children with special health care needs and follow-up on positive
      screening tests. CONCLUSIONS: Comprehensive, multimethod assessments are useful
      to identify health and safety needs and develop public health nursing
      interventions for ECE programs.

PMID- 20055964
TI  - Creating Project Talanoa: a culturally based community health program for U.S.
      Pacific Islander adolescents.
AB  - OBJECTIVE: This is an evaluation of the process and outcome of a research study
      to determine a culturally targeted health promotion program for U.S. Pacific
      Islander youth who are at risk for co-occurring problem behaviors, including
      risky sexual behavior, substance abuse, and interpersonal violence. DESIGN AND
      SAMPLE: An exploratory design was used and included qualitative interviews
      (N=54), focus groups (N=16), participant observation (over 3 years), and surveys
      (N=24) with Pacific Islander adults and youth. After identifying key cultural
      values and reviewing existing evidence-based prevention interventions, "Project
      Talanoa" was developed around 4 constructs: (1) cultural identity and pride, (2)
      teen health, (3) peer relations, and (4) family ties. The program was pilot
      tested and evaluated by 24 Pacific Islander adolescents (ages 12-15 years).
      RESULTS: Results indicate it was culturally appropriate, well liked by the
      participants, supported by parents and others in the community, and found to be
      feasible. CONCLUSIONS: Additional research is needed to test it for
      effectiveness. Project Talanoa provides a model for applying cultural concepts in
      the development of a risk reduction intervention for adolescents.

PMID- 20055965
TI  - Parental hesitation in immunizing children in Utah.
AB  - OBJECTIVES: To determine why parents in a Utah community hesitated in immunizing
      their children. DESIGN AND SAMPLE: Cross-sectional descriptive study. Data were
      collected from a convenience sample of 86 parents of under-immunized children in
      the county health department and local pediatric and family practice offices.
      MEASURES: Participants were asked to complete an immunization hesitancy survey
      including questions regarding why parents hesitated to immunize their children,
      parental concerns regarding immunizations, and what advice they would give to a
      friend or family member who had concerns about childhood vaccines. Parents could
      also write in any other comment, concern, or suggestion they had regarding
      childhood immunizations. RESULTS: 2 major themes were identified: concerns
      regarding immunization safety and lack of perceived need. The most commonly
      reported concerns regarding immunization safety included autism, immune system
      overload, and other adverse reactions. Many parents did not recognize the need
      for childhood immunizations, especially multiple immunizations given
      simultaneously on a strict timeline. CONCLUSIONS: The manner in which
      immunization information is shared with hesitant parents can be particularly
      important. There is a need for health care providers to assess and increase
      parental knowledge regarding immunizations.

PMID- 20055966
TI  - Building a community-academic partnership to improve health outcomes in an
      underserved community.
AB  - East Garfield Park, IL, is an impoverished community with 59.7% of residents
      falling below twice the poverty level and 42.6% of its children in poverty. In
      2001, the leading causes of hospitalizations were heart disease (10.3%), diabetes
      (2%), and asthma (3.9%), all of which occur at frequencies 33% greater than the
      Chicago average. Finally, a review of the health care facilities in the community
      suggests that there is a need for accessible primary health care services in the
      area. The purpose of this project was to improve health outcomes in an
      impoverished, underserved community with documented health care needs and lack of
      adequate health care services by creating a community-academic partnership to
      provide on-site, interdisciplinary, health care services within an established
      and trusted community-based social service agency, Marillac House. The short-term
      objectives for this project included creating a community-academic partnership
      between Marillac House and Colleges of Nursing, Medicine, and Health Sciences;
      providing comprehensive health care services; and developing an innovative
      clinical education model for interdisciplinary care across specialties. Long-term
      objectives included providing preventative services; evidenced-based management
      of acute and chronic illness; evaluating client's health outcomes; and creating a
      sustainability plan for the long-term success of the health center.

PMID- 20055967
TI  - Self-assessed emergency readiness and training needs of nurses in rural Texas.
AB  - OBJECTIVE: Nurses, particularly public health nurses, play a key role in
      emergency preparedness and response in rural areas. To prepare rural
      jurisdictions for unforeseen disastrous events it is imperative to assess the
      public health emergency readiness and training needs of nurses. The objective of
      this study was to assess the self-reported terrorism preparedness and training
      needs of a nurse workforce. DESIGN AND SAMPLE: Cross-sectional prevalence of
      practicing nurses in regions of North Texas. 3,508 rural nurses practicing in
      North Texas participated in the study. MEASUREMENTS: Data were collected through
      a mailed survey; analyses included multinominal logistic regression and
      descriptive statistics. RESULTS: A total of 941 (27%) nurses completed the
      survey. The majority of respondents reported limited bioterrorism-related
      training. Fewer than 10% were confident in their ability to diagnose or treat
      bioterrorism-related conditions. Although only 30% expressed a willingness to
      collaborate with state and local authorities during a bioterrorism event, more
      than 69% indicated interest in future training opportunities. Preferred training
      modalities included small group workshops with instructor-led training, and
      Internet-based training. CONCLUSIONS: Licensing agencies, professional
      organizations, and community constituencies may need to play a stronger role in
      improving the bioterrorism-related emergency preparedness of rural nurses.

PMID- 20055968
TI  - Exemptions for hookah bars in clean indoor air legislation: a public health
      concern.
AB  - Popularity of waterpipe smoking or hookah smoking in the United States has been
      growing for some time now among youth and young adults. Currently, many cities
      and states have exemptions that allow hookah bars to remain in operation despite
      the passage of clean indoor air legislation. From a public health perspective
      this is concerning for many reasons. One public health concern with the increase
      in popularity of this type of tobacco use is the associated health effects.
      Another concern is that hookah smoke produces a sweet smelling aroma making it
      less obvious that patrons and employees of hookah bars are inhaling noxious fumes
      from mainstream smoke, as well as the toxins from the charcoal that is used to
      heat the tobacco. The purpose of this paper is to discuss smoke-free air
      legislation in relation to hookah use, the public health implications of
      exempting hookah bars from current smoke-free legislation, and implications for
      the public health nurse in protecting the public from the dangers of second-hand
      smoke, and limiting this new form of tobacco use.

PMID- 20055969
TI  - Application of a partnership model for transformative and sustainable
      international development.
AB  - There are differences of intent and impact between short-term and long-term
      engagement of U.S. academic institutions with communities of need in developing
      nations. Global health programs that produce long-term transformative change
      rather than transient relief are more likely to be sustainable and in ethical
      harmony with expressed needs of a region or community. This article explores
      characteristics of successful ethical partnerships in global health and the
      challenges that threaten them, introducing a consensus community engagement model
      as a framework for building relationships, evolving an understanding of needs,
      and collaboratively developing solutions and responses to priority health needs
      in underserved regions of the world. The community engagement model is applied to
      a case study of an initiative by a U.S. school of nursing to establish long-term
      relationships with the nursing community in the Caribbean region with the goal of
      promoting transformative change through collaborative development of programs and
      services addressing health care needs of the region's growing elderly population
      and the increasing prevalence of noncommunicable chronic diseases. Progress of
      this ongoing long-term relationship is analyzed in the context of the
      organizational, philosophical, ethical, and resource commitments embodied in this
      approach to initiation of transformative and sustainable improvements in public
      health.

PMID- 20055970
TI  - Clergy knowledge and attitudes concerning faith community nursing: toward a three
      dimensional scale.
AB  - OBJECTIVE: Research has described faith community nursing practice, including
      positive aspects and barriers to practice. Barriers to faith community nursing
      practice must be identified and addressed to facilitate faith community nursing
      programs. The primary purpose of this study was to pilot test a newly developed
      instrument to measure knowledge and attitudes concerning faith community nursing.
      DESIGN AND SAMPLE: A survey design was used. The sample included clergy in the
      United Church of Christ (n=34). MEASURES: An investigator developed survey
      entitled Knowledge, Attitudes, and Opinions Concerning Faith Community Nursing
      was administered. RESULTS: Psychometric evaluation of the survey included content
      validity and internal consistency reliability for each of 3 scales. Coefficient
      alpha was high, ranging from .88 to .95. The results of the survey indicate that
      clergy, within the selected Christian denomination, generally have adequate
      knowledge and positive attitudes about faith community nursing. Knowledge scores
      on one item indicated some uncertainty among clergy about spiritual counseling as
      a nursing intervention. A major limitation to this study was the small,
      homogeneous sample. Future research should include further psychometric
      evaluation of validity and reliability in a larger, diverse sample. CONCLUSION:
      The results of this study indicate that, with further testing, the Knowledge,
      Attitudes, and Opinions Concerning Faith Community Nursing Survey has the
      potential to expand assessment of barriers to faith community nursing.

PMID- 20055971
TI  - Exercise adoption among older, low-income women at risk for cardiovascular
      disease.
AB  - Using an expanded Social Cognitive Theory (SCT) model, we hypothesized that self
      efficacy, outcome expectations, and exercise self-definition would predict
      exercise adoption. This secondary analysis examined data from a prospective
      single-group study of low-income women who received a physician screen and
      referral to a community-based, free exercise program. The sample included 190
      older, low-income women with a mean age of 64 years, the majority of whom were
      African American (66%) and had at least one cardiovascular risk factor (92%).
      Baseline values of self-efficacy, outcome expectations, and exercise self
      definition were measured using instruments developed for the study. Exercise
      adoption was defined as the number of exercise sessions completed over 8 weeks.
      Our hypothesis was tested using hierarchical multiple regression. The mean number
      of exercise sessions completed over the 8-week period was 5.7 out of a
      recommended 24. Value of Exercise scores, a subscale of the Exercise Self
      Definition scale, predicted exercise adoption. Self-efficacy and outcome
      expectations were not predictive. The significance of Value of Exercise scores
      reinforces the importance of expanding SCT with additional variables such as
      exercise self-definition. Future work should emphasize the social and
      environmental factors that form an important part of SCT.

PMID- 20055972
TI  - Academic faculty qualifications for community/public health nursing: an
      Association of Community Health Nursing Educators position paper.
AB  - The Association of Community Health Nursing Educators (ACHNE) has developed a
      number of documents designed to delineate the scope and function of
      community/public health nursing (C/PHN) educators, researchers, and
      practitioners. Consistent with the mission of ACHNE, this position paper entitled
      Academic Faculty Qualifications for Community/Public Health Nursing has been
      developed by the Faculty Qualifications Task Force. The shortage of qualified
      nursing faculty has been well documented. In particular, this shortage has
      increased the difficulty in having sufficient numbers of faculty who are
      educationally and experientially qualified to teach in the C/PHN specialty. ACHNE
      is addressing this concern by setting forth preferred qualifications for faculty
      to teach C/PHN at both the graduate and undergraduate level. While we recognize
      that the current faculty shortage may require schools to use faculty to teach in
      areas in which they do not have appropriate formal preparation, the paper
      outlines best practices for teaching C/PHN, a goal we urge all schools of nursing
      to work toward. Task Force members developed an earlier draft of the document in
      fall 2008, and input was solicited and received from ACHNE members and considered
      in the final document, which was approved by the ACHNE Executive Board in July
      2009.

PMID- 20055973
TI  - Research priorities for public health nursing.
AB  - The Association of Community Health Nursing Educators (ACHNE) Research Committee
      initiated a revision of the ACHNE Research Priorities for public health nursing
      practice in 2006, following those developed in 1992 and in 2000. The committee
      (a) reviewed public health nursing research abstracts (n=485) from 7 selected
      nursing journals to evaluate progress in addressing the 2000 Priorities; (b)
      identified research methods used, health issues and health behaviors addressed,
      and demographics of study populations in the abstracts; and (c) reviewed research
      priorities from key federal funding agencies and journal editors. Overall,
      progress toward meeting previous priorities was modest, with a limited range of
      methods, topics, and samples described. The 2009 ACHNE Research Priorities for
      public health nursing include: (1) Population-Focused Outcomes, and (2) Public
      Health Nursing Workforce. Multisite studies, clinical trials, community-based
      participatory research, development and/or analysis of existing large data sets,
      and development of valid and reliable methods are needed to address these
      priorities. Collaboration among educators, researchers, and practitioners is
      crucial to develop the scientific evidence base for population-based nursing
      practice.

PMID- 20055974
TI  - From the editors.

PMID- 20055975
TI  - Dick Wilson: applying uncommon sense to risks.

PMID- 20055976
TI  - Modeling logistic performance in quantitative microbial risk assessment.
AB  - In quantitative microbial risk assessment (QMRA), food safety in the food chain
      is modeled and simulated. In general, prevalences, concentrations, and numbers of
      microorganisms in media are investigated in the different steps from farm to
      fork. The underlying rates and conditions (such as storage times, temperatures,
      gas conditions, and their distributions) are determined. However, the logistic
      chain with its queues (storages, shelves) and mechanisms for ordering products is
      usually not taken into account. As a consequence, storage times-mutually
      dependent in successive steps in the chain-cannot be described adequately. This
      may have a great impact on the tails of risk distributions. Because food safety
      risks are generally very small, it is crucial to model the tails of (underlying)
      distributions as accurately as possible. Logistic performance can be modeled by
      describing the underlying planning and scheduling mechanisms in discrete-event
      modeling. This is common practice in operations research, specifically in supply
      chain management. In this article, we present the application of discrete-event
      modeling in the context of a QMRA for Listeria monocytogenes in fresh-cut iceberg
      lettuce. We show the potential value of discrete-event modeling in QMRA by
      calculating logistic interventions (modifications in the logistic chain) and
      determining their significance with respect to food safety.

PMID- 20055977
TI  - Decision making under uncertainty--an example for seismic risk management.
AB  - Decision-making techniques are used to select the "best" alternatives under
      multiple and often conflicting criteria. Multicriteria decision making (MCDM)
      necessitates to incorporate uncertainties in the decision-making process. The
      major thrust of this article is to extend the framework proposed by Yager for
      multiple decisionmakers and fuzzy utilities (payoffs). In addition, the concept
      of expert credibility factor is introduced. The proposed approach is demonstrated
      for an example of seismic risk management using a heuristic hierarchical
      structure. A step-by-step formulation of the proposed approach is illustrated
      using a hypothetical example and a three-story reinforced concrete building.

PMID- 20055978
TI  - Risk perception and movies: a study of availability as a factor in risk
      perception.
AB  - Media effects on risk perception have often been explained by Tversky and
      Kahneman's availability principle, but research has not consistently supported
      it. What seem like media effects based on availability may be effects of new
      information. In an experimental study, entertainment movies depicting dramatic
      risk events were shown. They were found to produce no average effects on
      perceived risks in spite of large mood effects and being perceived as credible.
      We found, however, evidence of idiosyncratic effects of the movies, that is,
      people reacted immediately after the movies with enhanced or diminished risk
      beliefs. These reactions had faded after 10 days. Implications for the
      availability heuristic and risk perception are discussed.

PMID- 20055980
TI  - There is no "I" in TEAM: working cooperatively to implement evidence into
      practice.

PMID- 20055981
TI  - A randomized phase II study of carboplatin plus pegylated liposomal doxorubicin
      versus carboplatin plus paclitaxel in platinum sensitive ovarian cancer patients:
      a Hellenic Cooperative Oncology Group study.
AB  - BACKGROUND: Platinum-based combinations are the standard second-line treatment
      for platinum-sensitive ovarian cancer (OC). This randomized phase II study was
      undertaken in order to compare the combination of carboplatin and pegylated
      liposomal doxorubicin (LD) with carboplatin and paclitaxel (CP) in this setting.
      METHODS: Patients with histologically confirmed recurrent OC, at the time of or
      more than 6 months after platinum-based chemotherapy, were randomized to six
      cycles of CP (carboplatin AUC5 + paclitaxel 175 mg/m2, d1q21) or CLD (carboplatin
      AUC5 + pegylated LD 45 mg/m2, d1q28). RESULTS: A total of 189 eligible patients
      (CP 96, CLD 93), with a median age of 63 years, median Performance Status (PS) 0
      and a median platinum free interval (PFI) of 16.5 months, entered the study.
      Discontinuation due to toxicity was higher in the CP patients (13.5% versus 3%, P
      = 0.016). The overall response rate was similar: CP 58% versus CLD 51%, P = 0.309
      (Complete Response; CR 34% versus 23%) and there was no statistical difference in
      time-to-progression (TTP) or overall survival (OS; TTP 10.8 months CP versus 11.8
      CLD, P = 0.904; OS 29.4 months CP versus 24.7 CLD, P = 0.454). No toxic deaths
      were recorded. Neutropenia was the most commonly seen severe toxicity (CP 30%
      versus CLD 35%). More frequent in CLD were severe thrombocytopenia (11% versus
      2%, P = 0.016), skin toxicity and Palmar-plantar erythrodysesthesia (PPE) grade 1
      2 (38% versus 9%, P< 0.001), while grade 3 neurotoxicity and alopecia were higher
      in CP (7% versus 0%, P = 0.029, 20% versus 5%, P = 0.003). PS and PFI were
      independent prognostic factors for TTP and OS. CONCLUSIONS: The combination of
      pegylated LD with carboplatin is effective, showing less neurotoxicity and
      alopecia than paclitaxel-carboplatin. It thus warrants a further phase III
      evaluation as an alternative treatment option for platinum-sensitive OC patients.
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry:
      ACTRN12609000436279.

PMID- 20055982
TI  - Risk factors associated with within-herd transmission of bovine leukemia virus on
      dairy farms in Japan.
AB  - BACKGROUND: Although several attempts have been made to control enzootic bovine
      leukosis (EBL) at the local level, a nationwide control program has not been
      implemented in Japan, except for passive surveillance. Effective control of EBL
      requires that the transmission routes of bovine leukemia virus (BLV) infection
      should be identified and intercepted based on scientific evidence. In this cross
      sectional study, we examined the risk factors associated with within-herd
      transmission of BLV on infected dairy farms in Japan. Blood samples taken from 30
      randomly selected adult cows at each of 139 dairy farms were tested by enzyme
      linked immunosorbent assay (ELISA). Information on herd management was collected
      using a structured questionnaire. RESULTS: Infected farms were defined as those
      with more than one ELISA-positive animal and accounted for 110 (79.1%) of the 139
      farms in the study. Completed questionnaires obtained from 90 of these 110 farms
      were used for statistical analysis. Seroprevalence, which was defined as the
      proportions of animals that tested positive out of all animals tested on the
      farm, was 17.1%, 48.1%, and 68.5% for the 25th, 50th, and 75th percentiles,
      respectively. A mixed logistic regression analysis implicated a loose housing
      system, dehorning, and a large number of horseflies in summer as risk factors
      (coefficient = 0.71, 1.11, and 0.82; p = 0.03, < 0.01, and 0.01, respectively)
      and feeding of colostrum to newborn calves from their dams as a protective factor
      (coefficient = -1.11, p = 0.03) against within-farm transmission of BLV on
      infected farms. CONCLUSION: Control of EBL in infected dairy farms in Japan will
      be improved by focusing particularly on these risk and protective factors.

PMID- 20055983
TI  - Impact of a synbiotic food on the gut microbial ecology and metabolic profiles.
AB  - BACKGROUND: The human gut harbors a diverse community of microorganisms which
      serve numerous important functions for the host wellbeing. Functional foods are
      commonly used to modulate the composition of the gut microbiota contributing to
      the maintenance of the host health or prevention of disease. In the present
      study, we characterized the impact of one month intake of a synbiotic food,
      containing fructooligosaccharides and the probiotic strains Lactobacillus
      helveticus Bar13 and Bifidobacterium longum Bar33, on the gut microbiota
      composition and metabolic profiles of 20 healthy subjects. RESULTS: The synbiotic
      food did not modify the overall structure of the gut microbiome, as indicated by
      Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE). The
      ability of the probiotic L. helveticus and B. longum strains to pass through the
      gastrointestinal tract was hypothesized on the basis of real-time PCR data. In
      spite of a stable microbiota, the intake of the synbiotic food resulted in a
      shift of the fecal metabolic profiles, highlighted by the Gas Chromatography Mass
      Spectrometry Solid Phase Micro-Extraction (GC-MS/SPME) analysis. The extent of
      short chain fatty acids (SCFA), ketones, carbon disulfide and methyl acetate was
      significantly affected by the synbiotic food consumption. Furthermore, the
      Canonical discriminant Analysis of Principal coordinates (CAP) of GC-MS/SPME
      profiles allowed a separation of the stool samples recovered before and after the
      consumption of the functional food. CONCLUSION: In this study we investigated the
      global impact of a dietary intervention on the gut ecology and metabolism in
      healthy humans. We demonstrated that the intake of a synbiotic food leads to a
      modulation of the gut metabolic activities with a maintenance of the gut
      biostructure. In particular, the significant increase of SCFA, ketones, carbon
      disulfide and methyl acetate following the feeding period suggests potential
      health promoting effects of the synbiotic food.

PMID- 20055984
TI  - The Zur regulon of Corynebacterium glutamicum ATCC 13032.
AB  - BACKGROUND: Zinc is considered as an essential element for all living organisms,
      but it can be toxic at large concentrations. Bacteria therefore tightly regulate
      zinc metabolism. The Cg2502 protein of Corynebacterium glutamicum was a candidate
      to control zinc metabolism in this species, since it was classified as
      metalloregulator of the zinc uptake regulator (Zur) subgroup of the ferric uptake
      regulator (Fur) family of DNA-binding transcription regulators. RESULTS: The
      cg2502 (zur) gene was deleted in the chromosome of C. glutamicum ATCC 13032 by an
      allelic exchange procedure to generate the zur-deficient mutant C. glutamicum
      JS2502. Whole-genome DNA microarray hybridizations and real-time RT-PCR assays
      comparing the gene expression in C. glutamicum JS2502 with that of the wild-type
      strain detected 18 genes with enhanced expression in the zur mutant. The
      expression data were combined with results from cross-genome comparisons of
      shared regulatory sites, revealing the presence of candidate Zur-binding sites in
      the mapped promoter regions of five transcription units encoding components of
      potential zinc ABC-type transporters (cg0041-cg0042/cg0043; cg2911-cg2912
      cg2913), a putative secreted protein (cg0040), a putative oxidoreductase
      (cg0795), and a putative P-loop GTPase of the COG0523 protein family (cg0794).
      Enhanced transcript levels of the respective genes in C. glutamicum JS2502 were
      verified by real-time RT-PCR, and complementation of the mutant with a wild-type
      zur gene reversed the effect of differential gene expression. The zinc-dependent
      expression of the putative cg0042 and cg2911 operons was detected in vivo with a
      gfp reporter system. Moreover, the zinc-dependent binding of purified Zur protein
      to double-stranded 40-mer oligonucleotides containing candidate Zur-binding sites
      was demonstrated in vitro by DNA band shift assays. CONCLUSION: Whole-genome
      expression profiling and DNA band shift assays demonstrated that Zur directly
      represses in a zinc-dependent manner the expression of nine genes organized in
      five transcription units. Accordingly, the Zur (Cg2502) protein is the key
      transcription regulator for genes involved in zinc homeostasis in C. glutamicum.

PMID- 20055985
TI  - Development of a self-reporting tool to obtain a combined index of severity of
      fibromyalgia (ICAF).
AB  - BACKGROUND: Fibromyalgia is a syndrome with heterogeneous symptoms. The
      evaluation in the clinical setting usually fails to cover the complexity of the
      syndrome. This study aims to determine how different aspects of fibromyalgia are
      inter-related when measured by means of a self-reporting tool. The objective is
      to develop a more complete evaluation model adjusted to the complexity and multi
      dimensional nature of the syndrome. METHODS: Application was made of the
      Fibromyalgia Impact Questionnaire, the Hospital Anxiety and Depression Scale, the
      Brief Pain Inventory, the Fatigue Assessment Scale, the Health Assessment
      Questionnaire, the General Health Questionnaire (GHQ-28), the Chronic Pain Coping
      Inventory, the Arthritis Self-efficacy Scale and the Sleep Quality Scale. An
      assessment was made, on the basis of clinical interviews, case histories and
      specific tests, of the patient sociodemographic data, comorbidity, physical
      exploration and other clinical indexes. An exploratory factor analysis was made,
      with comparisons of the clinical index scores in extreme groups of patients.
      RESULTS: The ICAF composed of 59 items was obtained, offering four factors that
      explain 64% of the variance, and referred to as Emotional Factor (33.7%),
      Physical-Activity (15%), Active Coping (9%) and Passive Coping (6.3%). A t-test
      between the extreme scores of these factors in the 301 patients revealed
      statistically significant differences in occupational status, medically
      unexplained syndromes, number of tender points, the six-minutes walk test,
      comorbidity and health care costs. CONCLUSIONS: This study offers a tool allowing
      more complete and rapid evaluation of patients with fibromyalgia. The test
      intrinsically evaluates the emotional aspects: anxiety and depression, and their
      impact upon social aspects. It also evaluates patient functional capacity,
      fatigue, sleep quality, pain, and the way in which the patient copes with the
      disease. This is achieved by means of a self-assessment questionnaire based on
      elements from well known tests.

PMID- 20055986
TI  - Forefoot disease activity in rheumatoid arthritis patients in remission: results
      of a cohort study.
AB  - INTRODUCTION: The aim of our study was to investigate the presence of disease
      activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid
      arthritis (RA) patients in remission according to the Disease Activity Score
      based on 28 joints (DAS28) remission criterion. METHODS: A total of 848 patients
      with recent-onset RA were included from 1995 through 2007. The DAS28 and pain and
      swelling of the MTP joints were assessed annually. The data were analyzed using
      descriptive techniques. RESULTS: On average, 35% of the patients fulfilled the
      remission criterion of DAS28 <2.6 during the first eight years of RA. On average,
      29% of these patients had at least one painful MTP joint and, on average, 31% had
      at least one swollen MTP joint during follow-up. Forty percent, on average, had
      at least one involved MTP joint (pain and/or swelling). CONCLUSIONS: Painful
      and/or swollen MTP joints were detected in a substantial proportion of patients
      classified as being in remission. Therefore, examination of the foot joints -
      irrespective of the patient's state of remission - seems indicated in order to
      provide optimal foot care.

PMID- 20055987
TI  - Antinociceptive effect of geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan
      17beta-oate methyl ester isolated from Pterodon pubescens Benth.
AB  - BACKGROUND: Pterodon pubescens Benth seeds are commercially available in the
      Brazilian medicinal plant street market. The crude alcoholic extracts of this
      plant are used in folk medicine as anti-inflammatory, analgesic, and anti
      rheumatic preparations. The aim of this study was to evaluate the contribution of
      geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl
      ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive
      activity of the crude extract. RESULTS: Compounds C1 and C2 demonstrated activity
      against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin
      (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests,
      demonstrating their contribution to the antinociceptive activity of crude
      Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2
      may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors.
      In hot-plate model, the antinociceptive activity was maintained when naloxone
      chloride (opioid antagonist) was administered prior to treatment with compounds
      suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in
      the hot-plate test via opioid receptors. The findings presented herein also
      suggest that compounds within the crude Pterodon pubescens Benth. extract may
      exert a synergistic interactive effect, since the crude extract (300 mg x kg-1)
      containing lower concentrations of compounds C1 (11.5%- 34.6 mg x kg-1) and C2
      (1.5% - 4.7 mg x kg-1) gave statistically the same effect to the pure compounds
      when tested separately (C1 = C2 = 300 mg.kg-1) in writhing experimental model
      with p.o. administration. Further studies will be undertaken to establish more
      specifically the mechanisms of action for compounds C1 and C2. Possible
      synergistic interactions will be evaluated employing the Isobole method.
      CONCLUSION: These results allowed us to establish a relationship between the
      popular use of Pterodon pubescens seeds for pain relief and the activity of two
      major compounds isolated from this species which demonstrated antinociceptive
      activity. Various "in vivo" experimental models corroborate the folk use of this
      species for different pain and inflammation disorders.

PMID- 20055988
TI  - The autism--tics, AD/HD and other comorbidities inventory (A-TAC): further
      validation of a telephone interview for epidemiological research.
AB  - BACKGROUND: Reliable, valid, and easy-to-administer instruments to identify
      possible caseness and to provide proxies for clinical diagnoses are needed in
      epidemiological research on child and adolescent mental health.The aim of this
      study is to provide further validity data for a parent telephone interview
      focused on Autism--Tics, Attention-deficit/hyperactivity disorder (AD/HD), and
      other Comorbidities (A-TAC), for which reliability and preliminary validation
      data have been previously reported. METHODS: Parents of 91 children clinically
      diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children
      and 319 children for whom clinical diagnoses had been previously assigned were
      interviewed by the A-TAC over the phone. Interviewers were blind to clinical
      information. Different scores from the A-TAC were compared to the diagnostic
      outcome. RESULTS: Areas under ROC curves for interview scores as predictors of
      clinical diagnoses were around 0.95 for most disorders, including autism spectrum
      disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic
      disorders, developmental coordination disorders (DCD) and learning disorders,
      indicating excellent screening properties. Screening cut-off scores with
      sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most
      conditions, as well as cut-off scores to identify proxies to clinical diagnoses
      with specificities above 0.90 (0.95 for ASD and AD/HD). CONCLUSIONS: The
      previously reported validity of the A-TAC was supported by this larger
      replication study using broader scales from the A-TAC-items and a larger number
      of diagnostic categories. Short versions of algorithms worked as well as larger.
      Different cut-off levels for screening versus identifying proxies for clinical
      diagnoses are warranted. Data on the validity for mood problems and oppositional
      defiant/conduct problems are still lacking. Although the A-TAC is principally
      intended for epidemiological research and general investigations, the instrument
      may be useful as a tool to collect information in clinical practice as well.

PMID- 20055989
TI  - Ventilation with lower tidal volumes as compared with conventional tidal volumes
      for patients without acute lung injury: a preventive randomized controlled trial.
AB  - INTRODUCTION: Recent cohort studies have identified the use of large tidal
      volumes as a major risk factor for development of lung injury in mechanically
      ventilated patients without acute lung injury (ALI). We compared the effect of
      conventional with lower tidal volumes on pulmonary inflammation and development
      of lung injury in critically ill patients without ALI at the onset of mechanical
      ventilation. METHODS: We performed a randomized controlled nonblinded preventive
      trial comparing mechanical ventilation with tidal volumes of 10 ml versus 6 ml
      per kilogram of predicted body weight in critically ill patients without ALI at
      the onset of mechanical ventilation. The primary end point was cytokine levels in
      bronchoalveolar lavage fluid and plasma during mechanical ventilation. The
      secondary end point was the development of lung injury, as determined by
      consensus criteria for ALI, duration of mechanical ventilation, and mortality.
      RESULTS: One hundred fifty patients (74 conventional versus 76 lower tidal
      volume) were enrolled and analyzed. No differences were observed in lavage fluid
      cytokine levels at baseline between the randomization groups. Plasma interleukin
      6 (IL-6) levels decreased significantly more strongly in the lower-tidal-volume
      group ((from 51 (20 to 182) ng/ml to 11 (5 to 20) ng/ml versus 50 (21 to 122)
      ng/ml to 21 (20 to 77) ng/ml; P = 0.01)). The trial was stopped prematurely for
      safety reasons because the development of lung injury was higher in the
      conventional tidal-volume group as compared with the lower tidal-volume group
      (13.5% versus 2.6%; P = 0.01). Univariate analysis showed statistical relations
      between baseline lung-injury score, randomization group, level of positive end
      expiratory pressure (PEEP), the number of transfused blood products, the presence
      of a risk factor for ALI, and baseline IL-6 lavage fluid levels and the
      development of lung injury. Multivariate analysis revealed the randomization
      group and the level of PEEP as independent predictors of the development of lung
      injury. CONCLUSIONS: Mechanical ventilation with conventional tidal volumes is
      associated with sustained cytokine production, as measured in plasma. Our data
      suggest that mechanical ventilation with conventional tidal volumes contributes
      to the development of lung injury in patients without ALI at the onset of
      mechanical ventilation. TRIAL REGISTRATION: ISRCTN82533884.

PMID- 20055990
TI  - Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia
      transformations.
AB  - BACKGROUND: Glutaminase predominates in periportal hepatocytes and it has been
      proposed that it determines the glutamine-derived nitrogen flow through the urea
      cycle. Glutamine-derived urea production should, thus, be considerably faster in
      periportal hepatocytes. This postulate, based on indirect observations, has not
      yet been unequivocally demonstrated, making a direct investigation of ureogenesis
      from glutamine highly desirable. METHODS: Zonation of glutamine metabolism was
      investigated in the bivascularly perfused rat liver with [U-14C]glutamine
      infusion (0.6 mM) into the portal vein (antegrade perfusion) or into the hepatic
      vein (retrograde perfusion). RESULTS: Ammonia infusion into the hepatic artery in
      retrograde and antegrade perfusion allowed to promote glutamine metabolism in the
      periportal region and in the whole liver parenchyma, respectively. The results
      revealed that the space-normalized glutamine uptake, indicated by (14)CO(2)
      production, gluconeogenesis, lactate production and the associated oxygen uptake,
      predominates in the periportal region. Periportal predominance was especially
      pronounced for gluconeogenesis. Ureogenesis, however, tended to be uniformly
      distributed over the whole liver parenchyma at low ammonia concentrations (up to
      1.0 mM); periportal predominance was found only at ammonia concentrations above 1
      mM. The proportions between the carbon and nitrogen fluxes in periportal cells
      are not the same along the liver acinus. CONCLUSIONS: In conclusion, the results
      of the present work indicate that the glutaminase activity in periportal
      hepatocytes is not the rate-controlling step of the glutamine-derived nitrogen
      flow through the urea cycle. The findings corroborate recent work indicating that
      ureogenesis is also an important ammonia-detoxifying mechanism in cells situated
      downstream to the periportal region.

PMID- 20055991
TI  - Seroepidemiology of human Toxoplasma gondii infection in China.
AB  - BACKGROUND: Toxoplasmosis is an important zoonotic parasitic disease worldwide.
      In immune competent individuals, Toxoplasma gondii preferentially infects tissues
      of central nervous systems, which might be an adding factor of certain
      psychiatric disorders. Congenital transmission of T. gondii during pregnancy has
      been regarded as a risk factor for the health of newborn infants. While in immune
      compromised individuals, the parasite can cause life-threatening infections. This
      study aims to investigate the prevalence of T. gondii infection among clinically
      healthy individuals and patients with psychiatric disorders in China and to
      identify the potential risk factors related to the vulnerability of infection in
      the population. METHODS: Serum samples from 2634 healthy individuals and 547
      patients with certain psychiatric disorders in Changchun and Daqing in the
      northeast, and in Shanghai in the south of China were examined respectively for
      the levels of anti-T. gondii IgG by indirect ELISA and a direct agglutination
      assay. Prevalence of T. gondii infection in the Chinese population in respect of
      gender, age, residence and health status was systematically analyzed. RESULTS:
      The overall anti-T. gondii IgG prevalence in the study population was 12.3%. In
      the clinically healthy population 12.5% was sero-positive and in the group with
      psychiatric disorders 11.3% of these patients were positive with anti-T. gondii
      IgG. A significant difference (P = 0.004) was found between male and female in
      the healthy population, the seroprevalence was 10.5% in men versus 14.3% in
      women. Furthermore, the difference of T. gondii infection rate between male and
      female in the 20-19 year's group was more obvious, with 6.4% in male population
      and 14.6% in female population. CONCLUSION: A significant higher prevalence of T.
      gondii infection was observed in female in the clinically healthy population. No
      correlation was found between T. gondii infection and psychiatric disorders in
      this study. Results suggest that women are more exposed to T. gondii infection
      than men in China. The data argue for deeper investigations for the potential
      risk factors that threat the female populations.

PMID- 20055992
TI  - SKPDB: a structural database of shikimate pathway enzymes.
AB  - BACKGROUND: The functional and structural characterisation of enzymes that belong
      to microbial metabolic pathways is very important for structure-based drug
      design. The main interest in studying shikimate pathway enzymes involves the fact
      that they are essential for bacteria but do not occur in humans, making them
      selective targets for design of drugs that do not directly impact humans.
      DESCRIPTION: The ShiKimate Pathway DataBase (SKPDB) is a relational database
      applied to the study of shikimate pathway enzymes in microorganisms and plants.
      The current database is updated regularly with the addition of new data; there
      are currently 8902 enzymes of the shikimate pathway from different sources. The
      database contains extensive information on each enzyme, including detailed
      descriptions about sequence, references, and structural and functional studies.
      All files (primary sequence, atomic coordinates and quality scores) are available
      for downloading. The modeled structures can be viewed using the Jmol program.
      CONCLUSIONS: The SKPDB provides a large number of structural models to be used in
      docking simulations, virtual screening initiatives and drug design. It is freely
      accessible at http://lsbzix.rc.unesp.br/skpdb/.

PMID- 20055993
TI  - Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T
      cell protein tyrosine phosphatase.
AB  - BACKGROUND: T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously
      expressed intra-cellular non-receptor protein tyrosine phosphatase involved in
      the negative regulation of several cancer relevant cellular signalling pathways.
      We have previously shown that interaction between the alpha-cytoplasmic tail of
      alpha1beta1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra
      molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP
      is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK
      signalling. However, this is challenging with low molecular weight compounds.
      METHODS: We developed a high-throughput compatible assay to analyse activity of
      recombinant TCPTP in vitro. Using this assay we have screened 64280 small
      molecules to identify novel agonists for TCPTP. Dose-dependent response to TCPTP
      agonist was performed using the in vitro assay. Inhibition effects and
      specificity of TCPTP agonists were evaluated using TCPTP expressing and null
      mouse embryonic fibroblasts. Western blot analysis was used to evaluate
      attenuation of PDGFRbeta and EGFR phosphorylation. Inhibition of VEGF signalling
      was analysed with VEGF-induced endothelial cell sprouting assays. RESULTS: From
      the screen we identified six TCPTP agonists. Two compounds competed with alpha1
      cytoplasmic domain for binding to TCPTP, suggesting that they activate TCPTP
      similar to alpha1-cyt by disrupting the intra-molecular bond in TCPTP.
      Importantly, one of the compounds (spermidine) displayed specificity towards
      TCPTP in cells, since TCPTP -/- cells were 43-fold more resistant to the compound
      than TCPTP expressing cells. This compound attenuates PDGFRbeta and VEGFR2
      signalling in cells in a TCPTP-dependent manner and functions as a negative
      regulator of EGFR phosphorylation in cancer cells. CONCLUSIONS: In this study we
      showed that small molecules mimicking TCPTP-alpha1 interaction can be used as
      TCPTP agonists. These data provide the first proof-of-concept description of the
      use of high-throughput screening to identify small molecule PTP activators that
      could function as RTK antagonists in cells.

PMID- 20055994
TI  - Evaluation of fecal mRNA reproducibility via a marginal transformed mixture
      modeling approach.
AB  - BACKGROUND: Developing and evaluating new technology that enables researchers to
      recover gene-expression levels of colonic cells from fecal samples could be key
      to a non-invasive screening tool for early detection of colon cancer. The current
      study, to the best of our knowledge, is the first to investigate and report the
      reproducibility of fecal microarray data. Using the intraclass correlation
      coefficient (ICC) as a measure of reproducibility and the preliminary analysis of
      fecal and mucosal data, we assessed the reliability of mixture density estimation
      and the reproducibility of fecal microarray data. Using Monte Carlo-based
      methods, we explored whether ICC values should be modeled as a beta-mixture or
      transformed first and fitted with a normal-mixture. We used outcomes from
      bootstrapped goodness-of-fit tests to determine which approach is less sensitive
      toward potential violation of distributional assumptions. RESULTS: The graphical
      examination of both the distributions of ICC and probit-transformed ICC (PT-ICC)
      clearly shows that there are two components in the distributions. For ICC
      measurements, which are between 0 and 1, the practice in literature has been to
      assume that the data points are from a beta-mixture distribution. Nevertheless,
      in our study we show that the use of a normal-mixture modeling approach on PT-ICC
      could provide superior performance. CONCLUSIONS: When modeling ICC values of gene
      expression levels, using mixture of normals in the probit-transformed (PT) scale
      is less sensitive toward model mis-specification than using mixture of betas. We
      show that a biased conclusion could be made if we follow the traditional approach
      and model the two sets of ICC values using the mixture of betas directly. The
      problematic estimation arises from the sensitivity of beta-mixtures toward model
      mis-specification, particularly when there are observations in the neighborhood
      of the the boundary points, 0 or 1. Since beta-mixture modeling is commonly used
      in approximating the distribution of measurements between 0 and 1, our findings
      have important implications beyond the findings of the current study. By using
      the normal-mixture approach on PT-ICC, we observed the quality of reproducible
      genes in fecal array data to be comparable to those in mucosal arrays.

PMID- 20055995
TI  - Quantitative relationship between the octanol/water partition coefficient and the
      diffusion limitation of the exchange between adipose and blood.
AB  - BACKGROUND: The goal of physiologically based pharmacokinetics (PBPK) is to
      predict drug kinetics from an understanding of the organ/blood exchange. The
      standard approach is to assume that the organ is "flow limited" which means that
      the venous blood leaving the organ equilibrates with the well-stirred tissue
      compartment. Although this assumption is valid for most solutes, it has been
      shown to be incorrect for several very highly fat soluble compounds which appear
      to be "diffusion limited". This paper describes the physical basis of this
      adipose diffusion limitation and its quantitative dependence on the blood/water
      (Kbld-wat) and octanol/water (Kow) partition coefficient. METHODS: Experimental
      measurements of the time dependent rat blood and adipose concentration following
      either intravenous or oral input were used to estimate the "apparent" adipose
      perfusion rate (FA) assuming that the tissue is flow limited. It is shown that
      the ratio of FA to the anatomic perfusion rate (F) provides a measure of the
      diffusion limitation. A quantitative relationship between this diffusion
      limitation and Kbld-wat and Kow is derived. This analysis was applied to
      previously published data, including the Oberg et. al. measurements of the rat
      plasma and adipose tissue concentration following an oral dose of a mixture of 13
      different polychlorinated biphenyls. RESULTS: Solutes become diffusion limited at
      values of log Kow greater than about 5.6, with the adipose-blood exchange rate
      reduced by a factor of about 30 for a solute with a log Kow of 7.36.
      Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose
      permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14
      micron aqueous layer separating the well-stirred blood from the adipose lipid.
      This is approximately equal to the thickness of the rat adipose capillary
      endothelium. CONCLUSIONS: These results can be used to quantitate the adipose
      blood diffusion limitation as a function of Kow. This is especially important for
      the highly fat soluble persistent organic chemicals (e.g. polychlorinated
      biphenyls, dioxins) whose pharmacokinetics are primarily determined by the
      adipose-blood exchange kinetics.

PMID- 20055996
TI  - Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked
      genes in gastrulating chicken embryos.
AB  - BACKGROUND: Considerable progress has been made in our understanding of sex
      determination and dosage compensation mechanisms in model organisms such as C.
      elegans, Drosophila and M. musculus. Strikingly, the mechanism involved in sex
      determination and dosage compensation are very different among these three model
      organisms. Birds present yet another situation where the heterogametic sex is the
      female. Sex determination is still poorly understood in birds and few key
      determinants have so far been identified. In contrast to most other species,
      dosage compensation of bird sex chromosomal genes appears rather ineffective.
      RESULTS: By comparing microarrays from microdissected primitive streak from
      single chicken embryos, we identified a large number of genes differentially
      expressed between male and female embryos at a very early stage (Hamburger and
      Hamilton stage 4), long before any sexual differentiation occurs. Most of these
      genes are located on the Z chromosome, which indicates that dosage compensation
      is ineffective in early chicken embryos. Gene ontology analyses, using an
      enhanced annotation tool for Affymetrix probesets of the chicken genome developed
      in our laboratory (called Manteia), show that among these male-biased genes found
      on the Z chromosome, more than 20 genes play a role in sex differentiation.
      CONCLUSIONS: These results corroborate previous studies demonstrating the rather
      inefficient dosage compensation for Z chromosome in birds and show that this
      sexual dimorphism in gene regulation is observed long before the onset of sexual
      differentiation. These data also suggest a potential role of non-compensated Z
      linked genes in somatic sex differentiation in birds.

PMID- 20055997
TI  - Estimation and efficient computation of the true probability of recurrence of
      short linear protein sequence motifs in unrelated proteins.
AB  - BACKGROUND: Large datasets of protein interactions provide a rich resource for
      the discovery of Short Linear Motifs (SLiMs) that recur in unrelated proteins.
      However, existing methods for estimating the probability of motif recurrence may
      be biased by the size and composition of the search dataset, such that p-value
      estimates from different datasets, or from motifs containing different numbers of
      non-wildcard positions, are not strictly comparable. Here, we develop more exact
      methods and explore the potential biases of computationally efficient
      approximations. RESULTS: A widely used heuristic for the calculation of motif
      over-representation approximates motif probability by assuming that all proteins
      have the same length and composition. We introduce pv, which calculates the
      probability exactly. Secondly, the recently introduced SLiMFinder statistic Sig,
      accounts for multiple testing (across all possible motifs) in motif discovery.
      However, it approximates the probability of all other possible motifs, occurring
      with a score of p or less, as being equal to p. Here, we show that the exhaustive
      calculation of the probability of all possible motif occurrences that are as rare
      or rarer than the motif of interest, Sig', may be carried out efficiently by
      grouping motifs of a common probability (i.e. those which have permuted orders of
      the same residues). Sig'v, which corrects both approximations, is shown to be
      uniformly distributed in a random dataset when searching for non-ambiguous
      motifs, indicating that it is a robust significance measure. CONCLUSIONS: A
      method is presented to compute exactly the true probability of a non-ambiguous
      short protein sequence motif, and the utility of an approximate approach for
      novel motif discovery across a large number of datasets is demonstrated.

PMID- 20055998
TI  - Snake mitochondrial genomes: phylogenetic relationships and implications of
      extended taxon sampling for interpretations of mitogenomic evolution.
AB  - BACKGROUND: Snake mitochondrial genomes are of great interest in understanding
      mitogenomic evolution because of gene duplications and rearrangements and the
      fast evolutionary rate of their genes compared to other vertebrates.
      Mitochondrial gene sequences have also played an important role in attempts to
      resolve the contentious phylogenetic relationships of especially the early
      divergences among alethinophidian snakes. Two recent innovative studies found
      dramatic gene- and branch-specific relative acceleration in snake protein-coding
      gene evolution, particularly along internal branches leading to Serpentes and
      Alethinophidia. It has been hypothesized that some of these rate shifts are
      temporally (and possibly causally) associated with control region duplication
      and/or major changes in ecology and anatomy. RESULTS: The near-complete
      mitochondrial (mt) genomes of three henophidian snakes were sequenced: Anilius
      scytale, Rhinophis philippinus, and Charina trivirgata. All three genomes share a
      duplicated control region and translocated tRNALEU, derived features found in all
      alethinophidian snakes studied to date. The new sequence data were aligned with
      mt genome data for 21 other species of snakes and used in phylogenetic analyses.
      Phylogenetic results agreed with many other studies in recovering several robust
      clades, including Colubroidea, Caenophidia, and Cylindrophiidae+Uropeltidae.
      Nodes within Henophidia that have been difficult to resolve robustly in previous
      analyses remained uncompellingly resolved here. Comparisons of relative rates of
      evolution of rRNA vs. protein-coding genes were conducted by estimating branch
      lengths across the tree. Our expanded sampling revealed dramatic acceleration
      along the branch leading to Typhlopidae, particularly long rRNA terminal branches
      within Scolecophidia, and that most of the dramatic acceleration in protein
      coding gene rate along Serpentes and Alethinophidia branches occurred before
      Anilius diverged from other alethinophidians. CONCLUSIONS: Mitochondrial gene
      sequence data alone may not be able to robustly resolve basal divergences among
      alethinophidian snakes. Taxon sampling plays an important role in identifying
      mitogenomic evolutionary events within snakes, and in testing hypotheses
      explaining their origin. Dramatic rate shifts in mitogenomic evolution occur
      within Scolecophidia as well as Alethinophidia, thus falsifying the hypothesis
      that these shifts in snakes are associated exclusively with evolution of a non
      burrowing lifestyle, macrostomatan feeding ecology and/or duplication of the
      control region, both restricted to alethinophidians among living snakes.

PMID- 20055999
TI  - Evaluation of the diagnostic performance of infrared imaging of the breast: a
      preliminary study.
AB  - BACKGROUND: The study was conducted to investigate the diagnostic performance of
      infrared (IR) imaging of the breast using an interpretive model derived from a
      scoring system. METHODS: The study was approved by the Institutional Review Board
      of our hospital. A total of 276 women (mean age = 50.8 years, SD 11.8) with
      suspicious findings on mammograms or ultrasound received IR imaging of the breast
      before excisional biopsy. The interpreting radiologists scored the lesions using
      a scoring system that combines five IR signs. The ROC (receiver operating
      characteristic) curve and AUC (area under the ROC curve) were analyzed by the
      univariate logistic regression model for each IR sign and an age-adjusted
      multivariate logistic regression model including 5 IR signs. The cut-off values
      and corresponding sensitivity, specificity, Youden's Index (Index =
      sensitivity+specificity-1), positive predictive value (PPV), negative predictive
      value (NPV) were estimated from the age-adjusted multivariate model. The most
      optimal cut-off value was determined by the one with highest Youden's Index.
      RESULTS: For the univariate model, the AUC of the ROC curve from five IR signs
      ranged from 0.557 to 0.701, and the AUC of the ROC from the age-adjusted
      multivariate model was 0.828. From the ROC derived from the multivariate model,
      the sensitivity of the most optimal cut-off value would be 72.4% with the
      corresponding specificity 76.6% (Youden's Index = 0.49), PPV 81.3% and NPV 66.4%.
      CONCLUSIONS: We established an interpretive age-adjusted multivariate model for
      IR imaging of the breast. The cut-off values and the corresponding sensitivity
      and specificity can be inferred from the model in a subpopulation for diagnostic
      purpose. TRIAL REGISTRATION: NCT00166998.

PMID- 20056000
TI  - Validation of reference genes for quantitative real-time PCR during leaf and
      flower development in Petunia hybrida.
AB  - BACKGROUND: Identification of genes with invariant levels of gene expression is a
      prerequisite for validating transcriptomic changes accompanying development.
      Ideally expression of these genes should be independent of the morphogenetic
      process or environmental condition tested as well as the methods used for RNA
      purification and analysis. RESULTS: In an effort to identify endogenous genes
      meeting these criteria nine reference genes (RG) were tested in two Petunia lines
      (Mitchell and V30). Growth conditions differed in Mitchell and V30, and different
      methods were used for RNA isolation and analysis. Four different software tools
      were employed to analyze the data. We merged the four outputs by means of a non
      weighted unsupervised rank aggregation method. The genes identified as optimal
      for transcriptomic analysis of Mitchell and V30 were EF1alpha in Mitchell and CYP
      in V30, whereas the least suitable gene was GAPDH in both lines. CONCLUSIONS: The
      least adequate gene turned out to be GAPDH indicating that it should be rejected
      as reference gene in Petunia. The absence of correspondence of the best-suited
      genes suggests that assessing reference gene stability is needed when performing
      normalization of data from transcriptomic analysis of flower and leaf
      development.

PMID- 20056001
TI  - Snazer: the simulations and networks analyzer.
AB  - BACKGROUND: Networks are widely recognized as key determinants of structure and
      function in systems that span the biological, physical, and social sciences. They
      are static pictures of the interactions among the components of complex systems.
      Often, much effort is required to identify networks as part of particular
      patterns as well as to visualize and interpret them.From a pure dynamical
      perspective, simulation represents a relevant way-out. Many simulator tools
      capitalized on the "noisy" behavior of some systems and used formal models to
      represent cellular activities as temporal trajectories. Statistical methods have
      been applied to a fairly large number of replicated trajectories in order to
      infer knowledge.A tool which both graphically manipulates reactive models and
      deals with sets of simulation time-course data by aggregation, interpretation and
      statistical analysis is missing and could add value to simulators. RESULTS: We
      designed and implemented Snazer, the simulations and networks analyzer. Its goal
      is to aid the processes of visualizing and manipulating reactive models, as well
      as to share and interpret time-course data produced by stochastic simulators or
      by any other means. CONCLUSIONS: Snazer is a solid prototype that integrates
      biological network and simulation time-course data analysis techniques.

PMID- 20056002
TI  - Comparative analysis of missing value imputation methods to improve clustering
      and interpretation of microarray experiments.
AB  - BACKGROUND: Microarray technologies produced large amount of data. In a previous
      study, we have shown the interest of k-Nearest Neighbour approach for restoring
      the missing gene expression values, and its positive impact of the gene
      clustering by hierarchical algorithm. Since, numerous replacement methods have
      been proposed to impute missing values (MVs) for microarray data. In this study,
      we have evaluated twelve different usable methods, and their influence on the
      quality of gene clustering. Interestingly we have used several datasets, both
      kinetic and non kinetic experiments from yeast and human. RESULTS: We underline
      the excellent efficiency of approaches proposed and implemented by Bo and co
      workers and especially one based on expected maximization (EM_array). These
      improvements have been observed also on the imputation of extreme values, the
      most difficult predictable values. We showed that the imputed MVs have still
      important effects on the stability of the gene clusters. The improvement on the
      clustering obtained by hierarchical clustering remains limited and, not
      sufficient to restore completely the correct gene associations. However, a common
      tendency can be found between the quality of the imputation method and the gene
      cluster stability. Even if the comparison between clustering algorithms is a
      complex task, we observed that k-means approach is more efficient to conserve
      gene associations. CONCLUSIONS: More than 6.000.000 independent simulations have
      assessed the quality of 12 imputation methods on five very different biological
      datasets. Important improvements have so been done since our last study. The
      EM_array approach constitutes one efficient method for restoring the missing
      expression gene values, with a lower estimation error level. Nonetheless, the
      presence of MVs even at a low rate is a major factor of gene cluster instability.
      Our study highlights the need for a systematic assessment of imputation methods
      and so of dedicated benchmarks. A noticeable point is the specific influence of
      some biological dataset.

PMID- 20056003
TI  - No significant effect on bone mineral density by high doses of vitamin D3 given
      to overweight subjects for one year.
AB  - BACKGROUND: In meta-analyses supplementation with vitamin D appears to reduce
      incidence of fractures, and in cross-sectional studies there is a positive
      association between serum 25-hydroxyvitamin D (25(OH)D) levels and bone mineral
      density (BMD). However, the effect of supplementation with high doses of vitamin
      D on BMD is more uncertain and could in theory have both positive and negative
      effects. METHODS: The study was a one year, double blind placebo-controlled
      intervention trial performed at the University Hospital of North Norway. 421
      subjects, 21 - 70 years old, were included and 312 completed the study. The
      subjects were randomized to vitamin D3 40.000 IU per week (DD group), vitamin D3
      20.000 IU per week (DP group), or placebo (PP group). All subjects were given 500
      mg calcium daily. Serum 25(OH)D, osteoprotegrin (OPG), receptoractivator of
      nuclear factor-kappaB ligand (RANKL), and BMD at the lumbar spine and the hip
      were measured before and at the end of the study. RESULTS: At baseline the mean
      serum 25(OH)D levels were 58 nmol/L (all subjects) and increased to 141 and 100
      nmol/L in the DD and DP groups, respectively. After one year, no significant
      differences were found between the three groups regarding change in BMD, serum
      OPG or RANKL. CONCLUSIONS: Supplementation with high doses of vitamin D for one
      year does not appear to have a negative effect on BMD in healthy subjects. In
      order to disclose a positive effect, subjects with low BMD and/or low serum
      25(OH)D levels need to be studied. TRIAL REGISTRATION: The trial was registered
      at ClinicalTrials.gov (NCT00243256).

PMID- 20056004
TI  - Pros and cons of estimating the reproduction number from early epidemic growth
      rate of influenza A (H1N1) 2009.
AB  - BACKGROUND: In many parts of the world, the exponential growth rate of infections
      during the initial epidemic phase has been used to make statistical inferences on
      the reproduction number, R, a summary measure of the transmission potential for
      the novel influenza A (H1N1) 2009. The growth rate at the initial stage of the
      epidemic in Japan led to estimates for R in the range 2.0 to 2.6, capturing the
      intensity of the initial outbreak among school-age children in May 2009. METHODS:
      An updated estimate of R that takes into account the epidemic data from 29 May to
      14 July is provided. An age-structured renewal process is employed to capture the
      age-dependent transmission dynamics, jointly estimating the reproduction number,
      the age-dependent susceptibility and the relative contribution of imported cases
      to secondary transmission. Pitfalls in estimating epidemic growth rates are
      identified and used for scrutinizing and re-assessing the results of our earlier
      estimate of R. RESULTS: Maximum likelihood estimates of R using the data from 29
      May to 14 July ranged from 1.21 to 1.35. The next-generation matrix, based on our
      age-structured model, predicts that only 17.5% of the population will experience
      infection by the end of the first pandemic wave. Our earlier estimate of R did
      not fully capture the population-wide epidemic in quantifying the next-generation
      matrix from the estimated growth rate during the initial stage of the pandemic in
      Japan. CONCLUSIONS: In order to quantify R from the growth rate of cases, it is
      essential that the selected model captures the underlying transmission dynamics
      embedded in the data. Exploring additional epidemiological information will be
      useful for assessing the temporal dynamics. Although the simple concept of R is
      more easily grasped by the general public than that of the next-generation
      matrix, the matrix incorporating detailed information (e.g., age-specificity) is
      essential for reducing the levels of uncertainty in predictions and for assisting
      public health policymaking. Model-based prediction and policymaking are best
      described by sharing fundamental notions of heterogeneous risks of infection and
      death with non-experts to avoid potential confusion and/or possible misuse of
      modelling results.

PMID- 20056005
TI  - Does the process map influence the outcome of quality improvement work? A
      comparison of a sequential flow diagram and a hierarchical task analysis diagram.
AB  - BACKGROUND: Many quality and safety improvement methods in healthcare rely on a
      complete and accurate map of the process. Process mapping in healthcare is often
      achieved using a sequential flow diagram, but there is little guidance available
      in the literature about the most effective type of process map to use. Moreover
      there is evidence that the organisation of information in an external
      representation affects reasoning and decision making. This exploratory study
      examined whether the type of process map - sequential or hierarchical - affects
      healthcare practitioners' judgments. METHODS: A sequential and a hierarchical
      process map of a community-based anti coagulation clinic were produced based on
      data obtained from interviews, talk-throughs, attendance at a training session
      and examination of protocols and policies. Clinic practitioners were asked to
      specify the parts of the process that they judged to contain quality and safety
      concerns. The process maps were then shown to them in counter-balanced order and
      they were asked to circle on the diagrams the parts of the process where they had
      the greatest quality and safety concerns. A structured interview was then
      conducted, in which they were asked about various aspects of the diagrams.
      RESULTS: Quality and safety concerns cited by practitioners differed depending on
      whether they were or were not looking at a process map, and whether they were
      looking at a sequential diagram or a hierarchical diagram. More concerns were
      identified using the hierarchical diagram compared with the sequential diagram
      and more concerns were identified in relation to clinical work than
      administrative work. Participants' preference for the sequential or hierarchical
      diagram depended on the context in which they would be using it. The difficulties
      of determining the boundaries for the analysis and the granularity required were
      highlighted. CONCLUSIONS: The results indicated that the layout of a process map
      does influence perceptions of quality and safety problems in a process. In
      quality improvement work it is important to carefully consider the type of
      process map to be used and to consider using more than one map to ensure that
      different aspects of the process are captured.

PMID- 20056006
TI  - Novel eukaryotic enzymes modifying cell-surface biopolymers.
AB  - BACKGROUND: Eukaryotic extracellular matrices such as proteoglycans,
      sclerotinized structures, mucus, external tests, capsules, cell walls and waxes
      contain highly modified proteins, glycans and other composite biopolymers. Using
      comparative genomics and sequence profile analysis we identify several novel
      enzymes that could be potentially involved in the modification of cell-surface
      glycans or glycoproteins. RESULTS: Using sequence analysis and conservation we
      define the acyltransferase domain prototyped by the fungal Cas1p proteins,
      identify its active site residues and unify them to the superfamily of classical
      10TM acyltransferases (e.g. oatA). We also identify a novel family of esterases
      (prototyped by the previously uncharacterized N-terminal domain of Cas1p) that
      have a similar fold as the SGNH/GDSL esterases but differ from them in their
      conservation pattern. CONCLUSIONS: We posit that the combined action of the
      acyltransferase and esterase domain plays an important role in controlling the
      acylation levels of glycans and thereby regulates their physico-chemical
      properties such as hygroscopicity, resistance to enzymatic hydrolysis and
      physical strength. We present evidence that the action of these novel enzymes on
      glycans might play an important role in host-pathogen interaction of plants,
      fungi and metazoans. We present evidence that in plants (e.g. PMR5 and ESK1) the
      regulation of carbohydrate acylation by these acylesterases might also play an
      important role in regulation of transpiration and stress resistance. We also
      identify a subfamily of these esterases in metazoans (e.g. C7orf58), which are
      fused to an ATP-grasp amino acid ligase domain that is predicted to catalyze, in
      certain animals, modification of cell surface polymers by amino acid or peptides.
      REVIEWERS: This article was reviewed by Gaspar Jekely and Frank Eisenhaber.

PMID- 20056007
TI  - Frequent aberrant DNA methylation of ABCB1, FOXC1, PPP2R2B and PTEN in ductal
      carcinoma in situ and early invasive breast cancer.
AB  - INTRODUCTION: Ductal carcinoma in situ (DCIS) is a non-invasive lesion of the
      breast that is frequently detected by mammography and subsequently removed by
      surgery. However, it is estimated that about half of the detected lesions would
      never have progressed into invasive cancer. Identifying DCIS and invasive cancer
      specific epigenetic lesions and understanding how these epigenetic changes are
      involved in triggering tumour progression is important for a better understanding
      of which lesions are at risk of becoming invasive. METHODS: Quantitative DNA
      methylation analysis of ABCB1, CDKN2A/p16INK4a, ESR1, FOXC1, GSTP1, IGF2, MGMT,
      MLH1, PPP2R2B, PTEN and RASSF1A was performed by pyrosequencing in a series of 27
      pure DCIS, 28 small invasive ductal carcinomas (IDCs), 34 IDCs with a DCIS
      component and 5 normal breast tissue samples. FOXC1, ABCB1, PPP2R2B and PTEN were
      analyzed in 23 additional normal breast tissue samples. Real-Time PCR expression
      analysis was performed for FOXC1. RESULTS: Aberrant DNA methylation was observed
      in all three diagnosis groups for the following genes: ABCB1, FOXC1, GSTP1, MGMT,
      MLH1, PPP2R2B, PTEN and RASSF1A. For most of these genes, methylation was already
      present at the DCIS level with the same frequency as within IDCs. For FOXC1
      significant differences in methylation levels were observed between normal breast
      tissue and invasive tumours (P < 0.001). The average DNA methylation levels were
      significantly higher in the pure IDCs and IDCs with DCIS compared to pure DCIS (P
      = 0.007 and P = 0.001, respectively). Real-time PCR analysis of FOXC1 expression
      from 25 DCIS, 23 IDCs and 28 normal tissue samples showed lower gene expression
      levels of FOXC1 in both methylated and unmethylated tumours compared to normal
      tissue (P < 0.001). DNA methylation levels of FOXC1, GSTP1, ABCB1 and RASSF1A
      were higher in oestrogen receptor (ER) positive vs. ER negative tumours; whereas
      methylation levels of FOXC1, ABCB1, PPP2R2B and PTEN were lower in tumours with a
      TP53 mutation. CONCLUSIONS: Quantitative methylation analysis identified ABCB1,
      FOXC1, PPP2R2B and PTEN as novel genes to be methylated in DCIS. In particular,
      FOXC1 showed a significant increase in the methylation frequency in invasive
      tumours. Low FOXC1 gene expression in both methylated and unmethylated DCIS and
      IDCs indicates that the loss of its expression is an early event during breast
      cancer progression.

PMID- 20056009
TI  - Pterygodermatites ( Multipectines) pluripectinata n. sp. (Spirurida:
      Rictulariidae), a nematode parasite of the crab-eating fox Cerdocyon thous
      (Linnaeus, 1766) from Caatinga shrubland, Brazil.
AB  - In a parasitological survey of free-ranging Cerdocyon thous (Carnivora: Canidae)
      from Brazilian Caatinga shrubland, a new species of Pterygodermatites
      (Multipectines) was recovered from the small intestine of this host.
      Morphological analysis showed that P. (Multipectines) pluripectinata n. sp. is
      distinguished from all other congeneric species mainly by the numerous plate-like
      projections and male caudal morphology and spicular length. There are few records
      on the occurrence of this genus in Neotropical regions.

PMID- 20056008
TI  - Evaluating clinical periodontal measures as surrogates for bacterial exposure:
      the Oral Infections and Vascular Disease Epidemiology Study (INVEST).
AB  - BACKGROUND: Epidemiologic studies of periodontal infection as a risk factor for
      cardiovascular disease often use clinical periodontal measures as a surrogate for
      the underlying bacterial exposure of interest. There are currently no
      methodological studies evaluating which clinical periodontal measures best
      reflect the levels of subgingival bacterial colonization in population-based
      settings. We investigated the characteristics of clinical periodontal definitions
      that were most representative of exposure to bacterial species that are believed
      to be either markers, or themselves etiologic, of periodontal disease. METHODS:
      706 men and women aged >or= 55 years, residing in northern Manhattan were
      enrolled. Using DNA-DNA checkerboard hybridization in subgingival biofilms,
      standardized values for Aggregatibacter actinomycetemcomitans, Porphyromonas
      gingivalis, Treponema denticola and Tannerella forsythia were averaged within
      mouth and summed to define "bacterial burden". Correlations of bacterial burden
      with clinical periodontal constructs defined by the severity and extent of
      attachment loss (AL), pocket depth (PD) and bleeding on probing (BOP) were
      assessed. RESULTS: Clinical periodontal constructs demonstrating the highest
      correlations with bacterial burden were: i) percent of sites with BOP (r = 0.62);
      ii) percent of sites with PD >or= 3 mm (r = 0.61); and iii) number of sites with
      BOP (r = 0.59). Increasing PD or AL severity thresholds consistently attenuated
      correlations, i.e., the correlation of bacterial burden with the percent of sites
      with PD >or= 8 mm was only r = 0.16. CONCLUSIONS: Clinical exposure definitions
      of periodontal disease should incorporate relatively shallow pockets to best
      reflect whole mouth exposure to bacterial burden.

PMID- 20056010
TI  - Effect of vancomycin-coated tympanostomy tubes on methicillin-resistant
      Staphylococcus aureus biofilm formation: in vitro study.
AB  - BACKGROUND AND OBJECTIVE: Bacterial biofilm formation has been implicated in the
      high incidence of persistent otorrhoea after tympanostomy tube insertion. It has
      been suggested that the tube material may be an important factor in the
      persistence of such otorrhoea. Development of methicillin-resistant
      Staphylococcus aureus otorrhoea after tympanostomy tube placement is a growing
      concern. We evaluated the effect of using vancomycin and chitosan coated
      tympanostomy tubes on the incidence of methicillin-resistant Staphylococcus
      aureus biofilm formation in vitro. MATERIALS AND METHODS: Three sets each of
      vancomycin-coated silicone tubes (n = 5), commercial silver oxide coated silicone
      tubes (n = 5) and uncoated tympanostomy tubes (as controls; n = 5) were compared
      as regards resistance to methicillin-resistant Staphylococcus aureus biofilm
      formation after in vitro incubation. RESULTS: Scanning electron microscopy showed
      that the surfaces of the silver oxide coated tubes supported the formation of
      thick biofilms with crusts, comparable to the appearance of the uncoated tubes.
      In contrast, the surface of the vancomycin-coated tympanostomy tubes was
      virtually devoid of methicillin-resistant Staphylococcus aureus biofilm.
      CONCLUSION: Vancomycin-coated tympanostomy tubes resist methicillin-resistant
      Staphylococcus aureus biofilm formation. Pending further study, such tubes show
      promise in assisting the control of methicillin-resistant Staphylococcus aureus
      biofilm formation.

PMID- 20056011
TI  - Nasal septal abscess and facial cellulitis caused by community-acquired
      methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: Community-acquired methicillin-resistant Staphylococcus aureus is
      emerging as an important pathogen. However, methicillin-resistant Staphylococcus
      aureus rarely causes nasal septal abscess. CASE REPORT: We present a case of
      severe, community-acquired, methicillin-resistant Staphylococcus aureus infection
      causing rapidly progressing sinusitis, nasal septal abscess and facial
      cellulitis. CONCLUSION: This report serves to remind the clinician of the
      expanding spectrum of severe infections caused by methicillin-resistant
      Staphylococcus aureus, all requiring prompt diagnosis and appropriate medical
      and/or surgical management.

PMID- 20056012
TI  - Securing a tracheostomy when circumferential ties may compromise flap perfusion:
      the 'epaulette' technique.
AB  - The use of free flaps in head and neck reconstruction raises the question of how
      to adequately fix a tracheostomy tube without causing local pressure to the
      vascular anastomosis. We describe a previously unreported technique of securing a
      tracheostomy tube in the immediate and early post-operative period without
      vascular compromise of the free flap, using the 'epaulette' technique. We
      undertook a PubMed literature search for articles describing similar methods of
      securing a tracheostomy tube in patients with head and neck free flaps, but found
      none. In our experience of using this method, we encountered no compromised flaps
      or unplanned extubations. We believe the epaulette technique to be an easy and
      safe method of securing a tracheostomy tube whilst simultaneously avoiding any
      local pressure effect on the free flap vessels and anastomosis.

PMID- 20056013
TI  - Measuring the incidence of adult community-acquired pneumonia in a Native
      American community.
AB  - Few population-based studies have investigated the epidemiology of adult
      community-acquired pneumonia (CAP). We aimed to determine the incidence of CAP in
      a population at high-risk for pneumococcal disease and to evaluate a standardized
      method for interpreting chest radiographs adapted from the World Health
      Organization paediatric chest radiograph interpretation guidelines. We reviewed
      radiology records at the two healthcare facilities serving the White Mountain
      Apache tribe to identify possible pneumonia cases > or =40 years of age. We
      categorized patients with clinical criteria and a physician diagnosis of
      pneumonia as clinical CAP and those with clinical criteria and an acute
      infiltrate as radiographic CAP. We identified 100 (27/1000 person-years) and 60
      (16/1000 person-years) episodes of clinical and radiographic CAP, respectively.
      The incidence of CAP increased with age. Both radiographic and clinical CAP were
      serious illnesses with more than half of patients hospitalized. Our case
      definitions and methods may be useful for comparing data across studies and
      conducting vaccine trials.

PMID- 20056014
TI  - Companion animals: a reservoir for methicillin-resistant Staphylococcus aureus in
      the community?
AB  - This article reviews the literature on the epidemiology of methicillin-resistant
      Staphylococcus aureus (MRSA) in dogs, cats and horses. Over the past 10 years,
      MRSA has emerged as an important pathogen in veterinary medicine, especially in
      countries with a high MRSA burden in human hospitals. During the same period,
      community-associated MRSA (CA-MRSA) infections in humans without apparent links
      to healthcare facilities have increased dramatically. Although animal infections
      occur outside human hospitals, significant epidemiological, clinical and genetic
      differences exist between CA-MRSA in humans and the majority of MRSA infections
      in the different animal species. The recognition of MRSA in animals has raised
      concern over their role as potential reservoirs or vectors for human MRSA
      infection in the community. However, available data on MRSA transmission between
      humans and companion animals are limited and the public health impact of such
      transmission needs to be the subject of more detailed epidemiological studies.

PMID- 20056015
TI  - Trends for influenza and pneumonia hospitalization in the older population: age,
      period, and cohort effects.
AB  - Birth cohort has been shown to be related to morbidity and mortality from other
      diseases and conditions, yet little is known about the potential for birth cohort
      in its relation to pneumonia and influenza (P&I) outcomes. This issue is
      particularly important in older adults, who experience the highest disease burden
      and most severe complications from these largely preventable diseases. The
      objective of this analysis is to assess P&I patterns in US seniors with respect
      to age, time, and birth cohort. All Medicare hospitalizations due to P&I (ICD-9CM
      codes 480-487) were abstracted and categorized by single-year of age and
      influenza year. These counts were then divided by intercensal estimates of age
      specific population levels extracted from the US Census Bureau to obtain age- and
      season-specific rates. Rates were log-transformed and linear models were used to
      assess the relationships in P&I rates and age, influenza year, and cohort. The
      increase in disease rates with age accounted for most of the variability by age
      and influenza season. Consistent relationships between disease rates and birth
      cohorts remained, even after controlling for age. Seasonal associations were
      stronger for influenza than for pneumonia. These findings suggest that there may
      be a set of unmeasured characteristics or events people of certain ages
      experienced contemporaneously that may account for the observed differences in
      P&I rates in birth cohorts. Further understanding of these circumstances and
      those resulting age and cohort groups most vulnerable to P&I may help to target
      health services towards those most at risk of disease.

PMID- 20056016
TI  - Schistosoma japonicum infection and rectal carcinoid tumour: underreported
      coincidence or neglected association?
AB  - Schistosoma japonicum infection associated with a rectal carcinoid in an
      asymptomatic 44-year-old female from the Philippines is described. A systematic
      review of the literature could not identify similar reports, suggesting a rare
      coincidence. However, epidemiological data on the frequency of both conditions as
      well as published results of a colorectal screening programme from China indicate
      that underreporting of this concurrence is likely. Moreover, several studies
      suggest a causal link between schistosomiasis caused by S. japonicum and more
      common gastrointestinal malignancies such as colorectal carcinoma. Hence the
      presented case and the apparent neglect of this observation in the current
      literature allow speculation on a role of S. japonicum in the pathogenesis of
      rare gastrointestinal neoplasms such as carcinoid tumours as well. Future reports
      on similar observations could help to determine the need for systematic
      investigations and are strongly encouraged.

PMID- 20056017
TI  - Epidemiology of nosocomial candidaemia in a university hospital: a 12-year study.
AB  - The incidence of nosocomial candidaemia was evaluated in a retrospective study in
      a Turkish tertiary-care hospital. Over a 12-year period (1996-2007), a total of
      743 episodes of candidaemia occurred in 743 patients, accounting for an average
      incidence of 1.9 episodes/1000 admissions and 2.9 episodes/10 000 patient-days
      per year. The annual incidence was almost constant during the study period except
      for 1996 when it was significantly higher in comparison with other years
      (P<0.05). The most common species isolated was Candida albicans (45%), followed
      by C. parapsilosis (26%), C. tropicalis (7%), C. krusei (7%), and C. glabrata
      (3.5%). A significant increase in C. albicans isolates causing candidaemia linked
      to a decrease in C. parapsilosis isolates in adult patients and C. krusei
      isolates in children was found between the two 6-year study periods. This trend
      reflects improved infection control at Uludag University Hospital. Ninety percent
      of isolates were susceptible to fluconazole (8 microg/ml) and resistance was
      found only in C. glabrata and C. parapsilosis isolates. Regular local
      surveillance of Candida spp. is important in order to develop empirical treatment
      protocols to reduce the incidence and mortality of candidaemia.

PMID- 20056018
TI  - Healthcare costs of Staphylococcus aureus and Clostridium difficile infections in
      veterans: role of vitamin D deficiency.
AB  - Clostridium difficile and staphylococcal infections are associated with increased
      morbidity, mortality and healthcare costs. Vitamin D deficiency may also
      contribute to increased healthcare costs. There is increasing evidence that
      vitamin D may have an antimicrobial role. We examined the relationship of serum
      25(OH)D levels to staphylococcal and C. difficile infections to determine if
      vitamin D deficiency was associated with adverse outcomes. In the outpatient
      setting, vitamin D deficiency in patients with C. difficile and staphylococcal
      infections were associated with significantly increased total outpatients costs
      and fee-based consultation. Laboratory expenses had a trend towards higher costs
      in the vitamin D-deficient group but did not reach statistical significance. The
      differences were most clearly seen in the in-patient group with enhanced
      laboratory, pharmacy and radiology costs. These differences resulted in vitamin D
      deficient patients with C. difficile or staphylococcal infections having costs
      more than five times higher than the non-deficient patients. The total length of
      hospital stay was four times greater in the vitamin D-deficient group. In
      addition, the total number of hospitalizations was also significantly greater in
      the vitamin D-deficient group. Surgery costs demonstrated a tendency to be higher
      in the vitamin D-deficient group but failed to reach statistical significance.
      Vitamin D deficiency is intimately linked to adverse health outcomes and costs in
      Veterans with staphylococcal and C. difficile infections in North East Tennessee.
      We recommend that vitamin D status be checked in patients with these infections
      and appropriate therapy be instituted to restore vitamin D level to normal in an
      expeditious manner.

PMID- 20056019
TI  - Human enterovirus 71 and hand, foot and mouth disease.
AB  - Hand, foot and mouth disease (HFMD) is generally a benign febrile exanthematous
      childhood disease caused by human enteroviruses. The route of transmission is
      postulated to be faeco-oral in developing areas but attributed more to
      respiratory droplet in developed areas. Transmission is facilitated by the
      prolonged environmental survival of these viruses and their greater resistance to
      biocides. Serious outbreaks with neurological and cardiopulmonary complications
      caused by human enterovirus 71 (HEV-71) seem to be commoner in the Asian Pacific
      region than elsewhere in the world. This geographical predilection is unexplained
      but could be related to the frequency of intra- and inter-typic genetic
      recombinations of the virus, the host populations' genetic predisposition,
      environmental hygiene, and standard of healthcare. Vaccine development could be
      hampered by the general mildness of the illness and rapid genetic evolution of
      the virus. Antivirals are not readily available; the role of intravenous
      immunoglobulin in the treatment of serious complications should be investigated.
      Monitoring of this disease and its epidemiology in the densely populated Asia
      Pacific epicentre is important for the detection of emerging epidemics due to
      enteroviruses.

PMID- 20056020
TI  - Temporal and right frontal lobe alterations in panic disorder: a quantitative
      volumetric and voxel-based morphometric MRI study.
AB  - BACKGROUND: With regard to current neurobiological theories, the aim of our study
      was to examine possible alterations of temporal and frontal lobe volume in panic
      disorder (PD). METHOD: Seventeen in-patients with PD and a group of healthy
      control subjects (HC) matched for age and gender were investigated by
      quantitative volumetric magnetic resonance imaging (MRI). Structures of interest
      were: the temporal lobe, the amygdala-hippocampus complex (AHC) and the frontal
      lobe. In addition, a voxel-based morphometry (VBM) analysis implemented in
      Statistical Parametric Mapping 5 (SPM5) was used for a more detailed assessment
      of possible volume alterations. Modulated grey matter (GM) images were used to
      test our a priori hypotheses and to present the volumetric results. RESULTS:
      Quantitative volumetric MRI revealed a bilateral reduction in temporal lobe
      volume in patients with PD compared to HC subjects. The AHC was normal. The right
      frontal lobe volume was also decreased. Using VBM we detected a significant GM
      volume reduction in the right middle temporal gyrus [Brodmann area (BA) 21] in
      patients with PD. In addition, there was a reduction in GM volume in the medial
      part of the orbitofrontal cortex (BA 11). CONCLUSIONS: Our results of reduced
      temporal and frontal lobe volume in PD are in agreement with prior studies. By
      using a recent VBM approach we were able to assess the abnormalities more
      precisely. The location of GM volume reduction in the right middle temporal gyrus
      and medial orbitofrontal cortex lends further support to recent aetiological
      models of PD.

PMID- 20056021
TI  - The DSM-IV definition of severity of major depression: inter-relationship and
      validity.
AB  - BACKGROUND: Severity is an important characteristic of major depression (MD) and
      an 'episode specifier' in DSM-IV classifying depressive episodes as 'mild',
      'moderate' or 'severe'. These severity subtypes rely on three different measures
      of severity: number of criteria symptoms, severity of the symptoms and degree of
      functional disability. No prior empirical study has evaluated the coherence and
      validity of the DSM-IV definition of severity of MD. METHOD: In a sample of 1015
      (518 males, 497 females) Caucasian twins from a population-based registry who met
      criteria for MD in the year prior to interview, factor analysis and logistic
      regression were conducted to examine the inter-relationships of the three
      severity measures and their associations with a wide range of potential
      validators including demographic factors, risk for future episodes, risk of MD in
      the co-twin, characteristics of the depressive episode, the pattern of co
      morbidity, and personality traits. RESULTS: Correlations between the three
      severity measures were significant but moderate. Factor analysis indicated the
      existence of a general severity factor, but the factor was not highly coherent.
      The three severity measures showed differential predictive ability for most of
      the validators. CONCLUSIONS: Severity of MD as defined by the DSM-IV is a
      multifaceted and heterogeneous construct. The three proposed severity measures
      reflect partly overlapping but partly independent domains with differential
      validity as assessed by a wide range of clinical characteristics. Clinicians
      should probably use a combination of severity measures as proposed in DSM-IV
      rather than privileging one.

PMID- 20056022
TI  - Impairment, disability, social support and depression among older parents in
      rural Thailand.
AB  - BACKGROUND: It is not known whether social support modifies the association
      between depression and impairment or disability in older people from developing
      countries in Asia. METHOD: We used a Thai version of the EURO-D scale to measure
      depression in 1104 Thai rural community-dwelling parents aged 60 years. These
      were all those providing data on depression who were recruited as part of a study
      of older adults with at least one living child (biological, stepchild or adopted
      child). Logistic regression modelling was used to determine: (a) whether
      impairment, disability and social support deficits were associated with
      depression; (b) whether social support modified this association. RESULTS: There
      were strong graded relationships between impairment, disability, social support
      deficits and EURO-D caseness. Level of impairment, but not disability, interacted
      with poor social support in that depression was especially likely in those who
      had more physical impairments as well as one or more social support deficits (p
      value for interaction=0.018), even after full adjustment. CONCLUSIONS: Social
      support is important in reducing the association between physical impairment and
      depression in Thai older adults, especially for those with a large number of
      impairments. Enhancing social support as well as improving healthcare and
      disability facilities should be emphasized in interventions to prevent depression
      in older adults.

PMID- 20056023
TI  - The role of stressful events in the development of behavioural and emotional
      problems from early childhood to late adolescence.
AB  - BACKGROUND: There is growing evidence on the importance of experiences of
      stressful events in the development of psychopathology. This study aimed to
      investigate the role of stressful events in the continuity of internalizing and
      externalizing problems, as well as the cross-influence of these problems from
      early childhood to late adolescence. METHOD: Data came from a general population
      sample of 396 children followed from the ages of 3 to 18 years. Parent-ratings of
      internalizing and externalizing problems at ages 3, 5, 10 and 18 years were used.
      Parents also reported on the presence of stressful events between the ages of 3
      and 5 years, and 5 and 10 years. Adolescent reports on stressful events over the
      ages of 10-18 years were used. Structural equation models were used to
      disentangle/analyse the role of stressful events in the development of
      internalizing and externalizing problems. RESULTS: From the age of 3 years
      onwards externalizing symptoms predicted experiences of stressful events. In
      turn, these experiences predicted later externalizing problems. Stressful events
      also explained part of the continuity of internalizing problems from the age of
      10 years onwards, but not during childhood. From childhood onwards, cross
      influences from externalizing problems to subsequent internalizing problems were
      found to run through stressful events. Only in adolescence cross-influences from
      internalizing problems to externalizing problems were found, again via stressful
      events. CONCLUSIONS: From childhood onwards to late adolescence, stressful events
      play a significant role in both the continuity and the co-occurrence of
      externalizing and internalizing problems. Theoretical and methodological
      implications of these findings are discussed.

PMID- 20056024
TI  - Neuronal correlates of affective theory of mind in schizophrenia out-patients:
      evidence for a baseline deficit.
AB  - BACKGROUND: Schizophrenia out-patients have deficits in affective theory of mind
      (ToM) but also on more basal levels of social cognition, such as the processing
      of neutral and emotional expressions. These deficits are associated with changes
      in brain activation in the amygdala and the superior temporal sulcus (STS).
      However, until now there have been no studies that examined these different
      levels of social cognition and their neurobiological underpinnings in patients
      within one design. METHOD: Sixteen medicated schizophrenia out-patients and 16
      matched healthy controls were studied with functional magnetic resonance imaging
      (fMRI) during a social cognition task that allows the investigation of affective
      ToM (aToM), emotion recognition and the processing of neutral facial expressions.
      RESULTS: Patients showed a deficit in emotion recognition and a more prominent
      deficit in aToM. The performance in aToM and in emotion recognition was
      correlated in the control group but not in the schizophrenia group. Region-of
      interest analysis of functional brain imaging data revealed no difference between
      groups during aToM, but a hyperactivation in the schizophrenia group in the left
      amygdala and right STS during emotion recognition and the processing of neutral
      facial expressions. CONCLUSIONS: The results indicate that schizophrenia out
      patients have deficits at several levels of social cognition and provide the
      first evidence that deficits on higher-order social cognitive processes in
      schizophrenia may be traced back to an aberrant processing of faces per se.

PMID- 20056025
TI  - Factors associated with deliberate self-harm among Irish adolescents.
AB  - BACKGROUND: Deliberate self-harm (DSH) is a major public health problem, with
      young people most at risk. Lifetime prevalence of DSH in Irish adolescents is
      between 8% and 12%, and it is three times more prevalent among girls than boys.
      The aim of the study was to identify the psychological, life-style and life event
      factors associated with self-harm in Irish adolescents. METHOD: A cross-sectional
      study was conducted, with 3881 adolescents in 39 schools completing an anonymous
      questionnaire as part of the Child and Adolescent Self-harm in Europe (CASE)
      study. There was an equal gender balance and 53.1% of students were 16 years old.
      Information was obtained on history of self-harm life events, and demographic,
      psychological and life-style factors. RESULTS: Based on multivariate analyses,
      important factors associated with DSH among both genders were drug use and
      knowing a friend who had engaged in self-harm. Among girls, poor self-esteem,
      forced sexual activity, self-harm of a family member, fights with parents and
      problems with friendships also remained in the final model. For boys,
      experiencing bullying, problems with schoolwork, impulsivity and anxiety
      remained. CONCLUSIONS: Distinct profiles of boys and girls who engage in self
      harm were identified. Associations between DSH and some life-style and life event
      factors suggest that mental health factors are not the sole indicators of risk of
      self-harm. The importance of school-related risk factors underlines the need to
      develop gender-specific initiatives in schools to reduce the prevalence of self
      harm.

PMID- 20056026
TI  - Rate of agreement between clinicians on the content of a cognitive formulation of
      delusional beliefs: The effect of qualifications and experience.
AB  - BACKGROUND: A key process in Cognitive Therapy (CT) is the development and
      sharing of a formulation. How clinicians develop formulations is under
      researched, particularly in working with people with psychosis. AIMS: This study
      investigated agreement between clinicians, when conceptualizing an individual's
      psychotic beliefs. It also explored whether agreement was dependent on
      qualifications and experience. METHOD: Eighty-two clinicians watched a video of
      an individual with delusional beliefs, and were asked to provide formulations
      using a CT template. These were compared with a "benchmark" formulation provided
      by three experts. RESULTS: There was good agreement for overt behaviours,
      emotions, and some aspects of early experience. However, identification of theory
      driven components such as core beliefs or assumptions was poorer. Greater
      clinical experience improved the agreement with the benchmark formulation
      overall, and greater CT specific experience improved formulation of the theory
      driven items. The more experience a clinician had of working with people with
      psychosis the lower the rate of agreement with the expert formulation.
      CONCLUSIONS: Formulation of delusional beliefs from a cognitive perspective is
      dependant on overall experience in cognitive therapy and not knowledge of
      psychosis, which may hinder performance. The implications for training in CT and
      psycho-social interventions are considered.

PMID- 20056027
TI  - Development and validation of a stability-indicating RP-UPLC method for the
      quantitative analysis of sparfloxacin.
AB  - A rapid, specific, and sensitive ultra-performance liquid chromatographic (UPLC)
      method for quantitative analysis of sparfloxacin in bulk drug and pharmaceutical
      formulations has been developed and validated. In this work, a new gradient
      reversed-phase chromatographic method was developed. The newly developed method
      is applicable for assay determination of the active pharmaceutical ingredient.
      The chromatographic separation of sparfloxacin was achieved on a Waters Acquity
      HSS T-3 column (100 x 2.1 mm, 1.8 microm) within a short runtime of 5 min. The
      method was validated according to the ICH guidelines with respect to system
      suitability, linearity, limit of quantitation and detection, precision, accuracy,
      robustness, and specificity. Forced degradation studies were also performed for
      sparfloxacin bulk drug samples to demonstrate the stability indicating power of
      the UPLC method. Comparison of system performance with conventional HPLC was made
      with respect to analysis time, efficiency, and sensitivity. The developed method
      was applied for the assay of marketed sparfloxacin formulations like tablets and
      eye drops.

PMID- 20056028
TI  - Determination of the residues of 18 carbamate pesticides in chestnut and pine nut
      by GPC cleanup and UPLC-MS-MS.
AB  - A new method using gel permeation chromatography (GPC) cleanup followed by ultra
      performance liquid chromatography combined with tandem mass spectrometry (UPLC-MS
      MS) has been established for simultaneous determination of 18 carbamate
      pesticides in nuts (chestnut and pine nut). Recoveries obtained by fortifying nut
      (spiking at 0.02 mg/kg) range from 70.21% to 89.56%. The proposed method features
      good sensitivity. Its limits of quantification are low enough to allow pesticide
      residues to be determined at concentrations below the maximum residue levels
      legally accepted. The precision, expressed as relative standard deviation, ranges
      from 2.26% to 4.07%.

PMID- 20056029
TI  - UHPLC separation with MS analysis for eight carbonyl compounds in mainstream
      tobacco smoke.
AB  - A method to quantify eight carbonyl compounds in mainstream cigarette smoke is
      presented using ultra-high pressure liquid chromatography (UHPLC). The
      combination of UHPLC and mass spectrometry (UHPLC-MS) dramatically reduces
      analysis times as compared to the current in-house high-performance liquid
      chromatography (HPLC)-UV method. In addition, improved detector selectivity and
      peak resolution are observed. Sample analysis times are reduced from 47 min with
      HPLC-UV to less than 5 min using this improved method. Atmospheric pressure
      chemical ionization, atmospheric pressure photo ionization, and electrospray
      ionization are directly compared to evaluate ionization potential and linear
      response range for the carbonyl 2,4-dinitrophenylhydrazine derivatives. Smoke
      extracts from three standard smoking protocols are analyzed by both UHPLC-MS and
      HPLC-UV for method comparison purposes.

PMID- 20056030
TI  - Applications of ultra-performance liquid chromatography to traditional Chinese
      medicines.
AB  - Ultra-performance liquid chromatography (UPLC), as a development of the
      chromatographic technique, was used in the quality control of Panax ginseng C.A.
      Mey. In the study, the UPLC methods were transferred from conventional high
      performance liquid chromatography (HPLC) methods according to chromatographic
      equations. The results demonstrated that UPLC analysis methods could be
      transferred from HPLC without loss of efficiency. Compared with conventional
      HPLC, UPLC made a surprising 10-fold increase in speed and 20-fold decrease in
      solvent consumption. The study indicated UPLC as a suitable alternative to HPLC
      and can be reliably applied to quality control of traditional Chinese medicines.

PMID- 20056031
TI  - Determination of para red, Sudan dyes, canthaxanthin, and astaxanthin in animal
      feeds using UPLC.
AB  - A simple high-performance liquid chromatography method was developed for
      quantitative determination of para red, Sudan I, Sudan II, Sudan III, Sudan IV,
      canthaxanthin, and astaxanthin in feedstuff. The sample was extracted using
      acetonitrile and cleaned up on a C(18) SPE column. The residues were analyzed
      using ultra-performance liquid chromatography coupled to a diode array detector
      at 500 nm. The mobile phase was acetonitrile-formic acid-water with a gradient
      elution condition. The external standard curves were calibrated. The mean
      recoveries of the seven colorants were 62.7-91.0% with relative standard
      deviation 2.6-10.4% (intra-day) and 4.0-13.2% (inter-day). The detection limits
      were in the range of 0.006-0.02 mg/kg.

PMID- 20056032
TI  - HPTLC determination of cefuroxime axetil and ornidazole in combined tablet dosage
      form.
AB  - A new simple high-performance thin layer chromatographic method for determination
      of cefuroxime axetil and ornidazole in combined tablet dosage form is developed
      and validated. Cefuroxime axetil is second-generation cephalosporin used to treat
      or prevent infections that are proven or strongly suspected to be caused by
      bacteria. Ornidazole is used to cure protozoan infections. The separation is
      carried out on Merck precoated silica gel aluminium plate 60 F(254) using toluene
      n-butanol-triethylamine (8.5:2:0.5, v/v/v) as mobile phase. Quantitative
      determination of drugs is carried out by densitometric scanning of plates at 285
      nm. The retention factor for ornidazole and cefuroxime axetil is found to be 0.51
      +/- 0.007 and 0.67 +/- 0.009, respectively. The method is validated with respect
      to linearity, accuracy, precision, and robustness. Response found to be linear in
      the concentration range of 100-500 ng/band for both cefuroxime axetil and
      ornidazole. The method has been successfully applied for the analysis of drugs in
      pharmaceutical formulation. The % assay is found to be 102.36 +/- 0.775 and
      101.00 +/- 1.192 for cefuroxime axetil and ornidazole, respectively.

PMID- 20056033
TI  - Titanium-coated silica spheres prepared by self-assembly technique for use as
      HPLC packing.
AB  - Titania-coated silica spheres were prepared by a layer-by-layer self-assembly
      technique for use as a high-performance liquid chromatography packing. This
      packing has a high surface area of 202.1 m(2)/g, a large pore volume of 0.36
      cm(3)/g, and a pore diameter of 7.0 nm. Furthermore, the packing particles
      exhibit narrow pore size distribution and good pore structure. The
      chromatographic behavior of the packing was studied under both normal and
      reversed-phase conditions. Low column pressures were observed. Aromatic isomeric
      compounds were well separated on the TiO(2)/SiO(2) column under normal phase
      conditions; pyridine and aniline derivatives were separated on the octadecyl
      bonded TiO(2)/SiO(2) (ODT) column, respectively, under reversed-phase conditions,
      and highly symmetrical peaks were obtained for 15 basic compounds. The chemical
      stability of the stationary phase was tested with sodium phosphate solution (10
      mmol/L, pH = 10) at 25 degrees C and potassium phosphate solution (50 mmol/L, pH
      = 10) at 50 degrees C.

PMID- 20056034
TI  - LC-MS-ESI for the determination of loratadine and descarboethoxyloratadine in
      human plasma.
AB  - A rapid, sensitive, and accurate liquid chromatography-tandem mass spectrometry
      assay for simultaneous determination of loratadine (L) and its active metabolite,
      descarboethoxyloratadine (DCL), in human plasma is developed using desipramine as
      internal standard (IS). The analytes and IS are separated on a Betabasic cyano
      (100 mm x 2.1 mm, 5 microm) column and detected by tandem mass spectrometry with
      a turbo ion spray interface operating in positive ion and multiple reaction
      monitoring acquisition mode. The total chromatographic runtime is 3.0 min with
      retention time for L, DCL, and IS at 0.82, 1.58, and 1.97 min, respectively. The
      method is validated over a dynamic linear range of 0.05-15.00 ng/mL for both L
      and DCL with a correlation coefficient of r(2) 0.9984 and 0.9979, respectively.
      The intra-batch and inter-batch precision (%CV) across five levels (LLOQ, LQC,
      MQC, HQC, and ULOQ) is less than 9%. The method is successfully applied to a
      bioequivalence study of 10 mg loratadine tablet formulation in 28 healthy Indian
      male subjects under fasted condition.

PMID- 20056035
TI  - Stability-indicating HPTLC determination of ambroxol hydrochloride in bulk drug
      and pharmaceutical dosage form.
AB  - A simple, selective, precise, and stability-indicating high-performance thin
      layer chromatographic (HPTLC) method for the analysis of ambroxol hydrochloride
      both as a bulk drug and in formulations was developed and validated. The method
      employed HPTLC aluminium plates precoated with silica gel 60F-254 as the
      stationary phase. The solvent system consisted of methanol-triethylamine (4:6
      v/v). The system was found to give a compact spot for ambroxol hydrochloride
      (R(f) value of 0.53 +/- 0.02). Densitometric analysis of ambroxol hydrochloride
      was carried out in the absorbance mode at 254 nm. The linear regression analysis
      data for the calibration plots showed good linear relationship with r(2) = 0.9966
      +/- 0.0013 with respect to peak area in the concentration range 100-1000 ng/spot.
      The mean value +/- standard deviation of slope and intercept were 164.85 +/- 0.72
      and 1168.3 +/- 8.26 with respect to peak area. The method was validated for
      precision, recovery, and robustness. The limits of detection and quantitation
      were 10 and 30 ng/spot, respectively. Ambroxol hydrochloride was subjected to
      oxidation and thermal degradation. The drug undergoes degradation under oxidation
      and heat conditions. This indicates that the drug is susceptible to oxidation and
      heat. Statistical analysis proves that the method is repeatable, selective, and
      accurate for the estimation of said drug. Stability indicating of new chemical
      entities is an important part for the drug development of ambroxol hydrochloride
      and for its estimation in plasma and other biological fluids; the novel
      Statistical analysis proves that the method is repeatable and selective for the
      analysis of ambroxol hydrochloride as bulk drug and in pharmaceutical
      formulations. The proposed developed HPTLC method can be applied for
      identification and quantitative determination of ambroxol hydrochloride in bulk
      drug and dosage forms. This work is to determine the purity of the drug available
      from the various sources by detecting the related impurities.

PMID- 20056036
TI  - Simultaneous determination of tetracaine, proline, and enoxacin in human urine by
      CE with ECL detection.
AB  - A simple, fast, and sensitive capillary electrophoresis method was developed for
      the simultaneous determination of tetracaine, proline, and enoxacin in human
      urine with electrochemiluminescence (ECL) detection. The effects of experimental
      conditions including the mode of applied voltage signal, the potential of working
      electrode, pH value, the flow rate of carrier of solution, the concentration of
      Ru(bpy)(3)(2+), and the ECL intensity of the drugs were investigated in detail.
      Parameters related to the separation and detection were investigated and
      optimized. Under optimized conditions, the proposed method displayed a linear
      range from 0.4 to 100 microg/mL for tetracaine, 0.2 to 80 microg/mL for proline,
      and 0.1 to 100 microg/mL for enoxacin. Their limits of detection were 0.08, 0.06,
      and 0.02 microg/mL, respectively. A baseline separation for tetracaine, proline,
      and enoxacin was achieved within 10 min. Developed method was successfully
      applied to determine tetracaine, proline, and enoxacin in human urine.

PMID- 20056037
TI  - Evaluation of IP-RP-HPLC for length determination of the trinucleotide repeat
      fragments in Huntington's disease.
AB  - Expansion of an unstable trinucleotide (CAG)(n) repeat region within exon 1 of
      the gene IT15 causes autosomal, dominantly inherited Huntington's disease (HD).
      The number of CAG-repeats varies from 6 to 35 in normal individuals, whereas in
      affected patients the expanded allele contains 40 or more CAG-repeats. Thus,
      exact determination of both alleles of the gene (normal and expanded) on the
      molecular level is of great importance for clinical diagnosis and prognosis
      regarding the course of the disease. In our study, we optimized and evaluated a
      highly sensitive, automated, and economical molecular method for length
      characterization of the trinucleotide fragment expansion such as (CAG)(n) repeat
      region based on ion-pair reversed-phase high-performance liquid chromatography
      (IP-RP-HPLC). We found that IP-RP-HPLC can be used for exact fragment length
      measuring between 60-280 bp as a sensitive and advantageous alternative method to
      conventional techniques.

PMID- 20056038
TI  - Simultaneous quantitative determination of cinnamaldehyde and methyl eugenol from
      stem bark of Cinnamomum zeylanicum Blume using RP-HPLC.
AB  - A simple, sensitive, and precise reversed-phase high performance liquid
      chromatographic (HPLC) method has been developed, validated and used for
      simultaneous quantitative determination of cinnamaldehyde and methyl eugenol from
      the methanolic extract of dried bark powder of Cinnamomum zeylanicum Blume
      (family Lauraceae). The ultrasonic extraction method was used for the extraction
      of these compounds. The reversed-phase HPLC analysis was carried out using a
      Intersil ODS-3V-C(18) (150 mm x 4.6 mm, 5 microm) column and a mobile phase
      comprising of methanol-acetonitrile-water in the volume ratio of 35:20:45,
      delivered at a flow rate of 1.0 cm(3)/min. The detection and quantitation of both
      the compounds was carried out at 221 nm.

PMID- 20056039
TI  - Development and validation of a confirmatory HPLC method for simultaneous
      determination of Sudan dyes in animal tissues and eggs.
AB  - A simple and sensitive high-performance liquid chromatography (HPLC) analytical
      method for the simultaneous determination of six Sudan dyes (Sudan Red G, Sudan
      I, Sudan II, Sudan III, Sudan Red 7B, Sudan IV) in animal tissues and eggs was
      developed. Samples were extracted with acetonitrile followed by a cleanup using a
      C(18) solid-phase extraction column. Chromatographic separation was achieved on a
      Zorbax SB-C(18) column under gradient conditions. The analytes were detected at
      510 nm by HPLC with diode array detection. Specificity, decision limit (CCalpha),
      detection capacity (CCbeta), accuracy, and precision were determined during
      validation process. Recoveries for six Sudan dyes from three animal tissues and
      eggs were 77.2-98.0% with excellent relative standard deviations. CCalpha and
      CCbeta were in the range of 7.7-9.0 microg/kg and 9.1-10.3 microg/kg,
      respectively. The limits of quantitations were between 12.8 microg/kg and 15.0
      microg/kg.

PMID- 20056040
TI  - Selective densitometric determination of four alpha-aminocephalosporins using
      ninhydrin reagent.
AB  - A simple, selective, and precise densitometric method for analysis of four alpha
      aminocephalosporins, namely cefaclor monohydrate, cefadroxil monohydrate,
      cefalexin anhydrous, and cefradine anhydrous, both in bulk drugs and in
      formulations was developed and validated. The method employed thin-layer
      chromatography (TLC) aluminium sheets precoated with silica gel G 60 F(254) as
      the stationary phase. The solvent system consists of ethyl acetate-methanol-water
      with different ratios for all studied drugs (R(f) values of 0.40-0.60). The
      separated spots were visualized as blue to violet color after spraying with
      ninhydrin reagent. The linear regression analysis data for the calibration plots
      of all studied drugs produced a good linear relationship with correlation
      coefficients ranging from 0.9990 to 0.9996 and coefficients of determination
      ranging from 0.9986 to 0.9992 over the concentration range 2-10 microg/spot. The
      limits of detection and quantitation for all studied drugs ranged from 0.09 to
      0.23 and from 0.27 to 0.84 microg/spot, respectively. The developed method was
      applied successfully for the determination of the studied drugs in their
      pharmaceutical dosage forms with good precision and accuracy. Also, the method
      can be employed as a promising stability-indicating assay.

PMID- 20056041
TI  - Simultaneous analysis of xanthone glycosides in Halenia elliptica by HPLC-DAD-ESI
      MS.
AB  - A new, simple, and sensitive high-performance liquid chromatography-diode array
      detector (HPLC-DAD) method was developed for the simultaneous determination of
      six major xanthone glycosides in Halenia elliptica. The chemical profile of six
      xanthone glycosides, including 2,3,5-trimethoxy-1-O-primeverosyloxyxanthone
      (Analyte 1), 2,3,4,5-tetramethoxy-1-O-primeverosyloxyxanthone (Analyte 2),
      2,3,5,7-tetramethoxy-1-O-primeverosyloxyxanthone (Analyte 3), 2,3,7-trimethoxy-1
      O-primeverosyloxyxanthone (Analyte 4), 2,3,4,7-tetramethoxy-1-O-primeverosyloxy
      xanthone (Analyte 5), and 2,3,4,5,7-pentamethoxy-1-O-primeverosyloxy-xanthone
      (Analyte 6) were acquired by using HPLC-DAD coupled to an electrospray ionization
      mass spectrometer. The analysis was performed on a Kromasil C(18) column (5
      microm, 250 x 4.6 mm i.d.), using acetonitrile-H(2)O (25:75, v/v) as the mobile
      phase at a flow rate of 0.8 mL/min. Under UV detection at 260 nm, the recoveries
      of the analytes were in the range of 96.1-100.3%, the LODs were within 0.20
      microg/mL, and all the xanthone glycosides showed good linearity (r > or =
      0.9990) in a relatively wide concentration range; the intra-day relative standard
      deviations (%) ranged from 0.65 to 1.39%, and the inter-day RSDs% were not higher
      than 5%. The proposed method is suitable for quantitative and qualitative
      determination of the xanthone glycosides in H. elliptica.

PMID- 20056042
TI  - Pre-operative diagnosis of obturator hernia: a report of two cases.
AB  - Obturator hernias are rare, accounting for less than 1.5% of all hernias, and
      usually present with acute intestinal obstruction requiring emergency surgery.
      They are rarely diagnosed in the elective setting. We discuss two cases, a 52
      year-old man and a 71-year-old woman, both presenting electively with a history
      suggestive of occult groin hernia; neither had a palpable lump. They both
      underwent out-patient herniography which demonstrated obturator hernia and both
      patients subsequently had elective laparoscopic repair, with good results. A high
      index of suspicion along with appropriate use of imaging modality allows for
      early identification of this rare condition. Early intervention can prevent the
      morbidity and mortality associated with complicated obturator hernia.

PMID- 20056044
TI  - Laparoscopic repair of spontaneous vaginal evisceration of small bowel: report of
      a case.
AB  - Spontaneous vaginal evisceration of the small bowel is a rare event. It is
      precipitated in the postmenopausal woman commonly by hysterectomy and in the
      premenopausal woman by vaginal trauma. We report a case of a 75-year-old woman
      presenting with a protruding mass in her vagina and associated abdominal pain. A
      combined laparoscopic and transvaginal method of repair is described and the
      advantage of using both techniques highlighted.

PMID- 20056045
TI  - Robotic surgery.

PMID- 20056046
TI  - Post-traumatic appendicular-cutaneous fistula: a case report.
AB  - Appendicular-cutaneous fistula is an uncommon condition that usually occurs as a
      complication of appendicitis. We report the case of a 28-year-old woman with a
      chronic appendicular-cutaneous fistula following a road traffic accident in which
      she sustained a penetrating injury to the abdomen.

PMID- 20056047
TI  - A dislocated mobile bearing from a unicondylar knee replacement--a complication
      not to be missed.
AB  - A case is described of a dislocated mobile bearing from a unicondylar knee
      replacement missed on initial radiograph examination. It is important to identify
      this complication early to eliminate pain and prevent premature prosthesis and
      peri-articular destruction.

PMID- 20056048
TI  - Critical appraisal of subjective outcome measures used in the assessment of
      shoulder disability.
AB  - INTRODUCTION: Objective measures can be impractical in some settings, because
      they are time consuming and require face-to-face contact. More recently, there is
      an increasing trend towards the use of subjective outcome measures. Hence, in
      this article, five common subjective shoulder outcome measures are critically
      appraised in terms of their development, validity, reliability, responsiveness
      and clinical application. MATERIALS AND METHODS: Following an extensive
      literature search, five common shoulder patient-based scores were identified:
      Disability of Arm, Shoulder and Hand (DASH), Oxford Shoulder Score (OSS),
      Shoulder Disability Questionnaire (SDQ-UK), Shoulder Pain and Disability Index
      (SPADI), and the Shoulder Rating Questionnaire (SRQ). These questionnaires were
      then critically appraised in terms of their development process, validity,
      reliability, responsiveness, and clinical application. RESULTS: The SDQ-UK has
      shown good construct validity but there is no data available regarding internal
      consistency, reliability and responsiveness. The SPADI has good internal
      consistency, fair reliability with adequate criterion and construct validity. The
      DASH has shown to have good construct validity, excellent test-re-test
      reliability and responsiveness to change. The OSS has good sensitivity, validity
      and responsiveness. Though SRQ has good internal consistency, its reproducibility
      and responsiveness are poor. CONCLUSIONS: Based on this critical appraisal, the
      DASH received the best ratings for its clinimetric properties followed by the
      OSS.

PMID- 20056049
TI  - A striking response of anorectal melanoma to radiotherapy (locoregional disease
      confined to perineum and anal canal).
AB  - Anorectal melanoma is a rare disease with an exceedingly poor prognosis.
      Literature evaluating outcomes is often difficult because of the infrequent
      diagnosis, delayed presentation and almost universally poor outcome. We describe
      a case of a 78-year-old woman with a large anorectal melanoma without detectable
      metastasis following radiological investigation. Due to the patient's co
      morbidity, radiotherapy of 36 Gy once weekly over 7 weeks, was given as the sole
      treatment. The clinical outcome showed a remarkable regression of the tumour
      without radiological or clinical recurrence at 12 months' follow-up. This is the
      first case of the successful use of radiotherapy alone in anorectal melanoma.

PMID- 20056050
TI  - Chronic groin sinus: an unusual complication of sterilisation clips.
AB  - We report the case of a patient presenting with a chronic groin sinus secondary
      to a tubal ligation clip migration (Filshie clip) 21 years after the laparoscopic
      sterilisation took place. Our case report adds to the small number of cases
      describing tubal clip migration with resultant local sepsis. Although this is a
      rare complication, it should be borne in mind for women who have undergone tubal
      clip ligation and present with recurrent or chronic groin, perineal or peri-anal
      sepsis.

PMID- 20056052
TI  - Mesenteric and coeliac occlusions following heparin-induced thrombocytopenia
      after aortobiprofunda bypass surgery.
AB  - A 56-year-old man developed mid-gut bowel ischaemia following an elective
      aortobiprofunda bypass for short-distance claudication. The bowel was resected
      and he was commenced on lifelong total parenteral nutrition. He was found to have
      developed heparin-induced thrombocytopenia and thrombosis, confirmed by high
      levels of heparin-platelet factor 4-antibody on enzyme-linked immunosorbent assay
      (ELISA). He subsequently had foregut ischaemia with a second bout of
      thrombocytopenia despite not being on heparin. The case describes the first
      report of bowel ischaemia as a consequence of heparin-induced thrombocytopenia
      causing sequential superior mesenteric and coeliac arterial thrombosis in this
      scenario and highlights the importance of the awareness of the association of
      these pathological entities and subsequent management.

PMID- 20056053
TI  - A rare clinical presentation of a malignant fibrous histiocytoma within the
      iliopsoas muscle.
AB  - Primary malignant tumours of the iliopsoas compartment are rare clinical entities
      that are infrequently reported in the literature. Although presenting symptoms
      vary, this is a very uncommon report of referred pain to the groin and testicular
      region in a psoas muscle tumour.

PMID- 20056054
TI  - A modification of the standard midline posterior approach to the intertransverse
      area of the lumbar spine.
AB  - A midline approach to the lumbar region is most frequently used for posterior
      lumbar spine surgery. The exposure of the deeper layer of muscles, however, is
      imprecise and can entail substantial tissue damage and blood loss. During 10
      years of operative surgical experience, we have developed an improved and less
      traumatic technique for exposure of the lumbar transverse processes and
      intertransverse region in which the tendons of multifidus and longissimus muscles
      are isolated at every level and divided laterally to the facet joints. This
      method eases identification and accurate cauterisation of the subjacent arteries,
      thereby reducing tissue damage and blood loss. It takes no more time and
      clarifies the exposure of the lumbar transverse processes and intertransverse
      region. Cadaveric dissection confirms the muscular and arterial anatomy of the
      region. We recommend use of this modified approach to improve standard practice.

PMID- 20056055
TI  - An extreme presentation of pancreatic pseudocyst.
AB  - Pancreatitis is a serious and common presentation to general surgery departments.
      There are many complications associated with pancreatitis and we present an
      undescribed presentation of a pancreatic pseudocyst and include its management
      strategy.

PMID- 20056056
TI  - Small flake, big problem: an unreported cause of extensor pollicis longus tendon
      rupture.
AB  - Fracture of the base of the third metacarpal with associated avulsion of the
      extensor carpi radialis brevis tendon is a rare injury. We report such a fracture
      and the unusual resulting complication of division of the extensor pollicis
      longus tendon by the avulsed bony fragment. Careful monitoring using lateral
      radiographs is needed to make the diagnosis and displacement of the avulsed
      fragment warrants open reduction and internal fixation.

PMID- 20056057
TI  - Rapunzel syndrome and gastric perforation.
AB  - Rapunzel syndrome complicated with gastric perforation is a very rare
      presentation of trichobezoar. Trichobezoar is an uncommon condition affecting
      predominantly females. It has non-specific clinical presentation, a wide range of
      complications, and, if not treated appropriately, carries significant mortality.
      Traditional treatment of trichobezoar is surgical, though, attempts have been
      made to excise endoscopically, dissolve chemically or fragment using
      extracorporeal shock waves. We report a case of a very large trichobezoar
      occupying most of the stomach and duodenum complicated with gastric perforation,
      and summarise the literature regarding trichobezoar aetiology, diagnostic
      difficulties, and management.

PMID- 20056058
TI  - Early results of whole femoral head allograft with articular cartilage for
      acetabular impaction grafting in revision hip replacements.
AB  - INTRODUCTION: Extensive bone loss associated with revision hip surgery is a
      significant orthopaedic challenge. Acetabular reconstruction with the use of
      impaction bone grafting and a cemented polyethylene cup is a reliable and durable
      technique in revision situations with cavitatory acetabular bone defects. Some
      use cancellous graft alone whilst others morselise the whole femoral head after
      removal of articular cartilage. This paper asks, if it really necessary to use
      pure cancellous graft? PATIENTS AND METHODS: Forty-two acetabular revisions using
      impacted morselized bone graft without removal of articular cartilage and a
      cemented cup were studied retrospectively. The mean follow-up was 3 years (range,
      2-5.6 years). Clinical and radiographic assessment was made using the Oxford hip
      score, Hodgkinson's criteria (1988) for socket loosening and the Gie
      classification (1993) for evaluation of allograft consolidation and remodelling.
      RESULTS: Forty (95%) sockets were considered radiologically stable (type 0, 1, 2
      demarcations) and two (5%) sockets were radiologically loose (Type 3
      demarcation). There was no socket migration in our series. Twenty-seven(64%)
      cases showed good trabecular remodelling (grade 3). Twelve (29%) cases showed
      trabecular incorporation (grade 2). Only three (7%) cases showed poor allograft
      incorporation (grade 1). Average pre-operative Oxford hip score was 41 and
      postoperative hip score was 27. There have been no socket re-revisions (100%
      survival) at an average of 3 years. CONCLUSIONS: Early radiological and clinical
      survival results with retaining articular cartilage of femoral head allografts
      are similar and comparable to other major studies for acetabular impaction bone
      grafting in revisions. Minimal loss of allograft mass is 40% in obtaining pure
      cancellous graft. When there is a limited supply and demand of allograft, saving
      up to 40% of the material is a valuable and cost-effective use of scarce
      resources.

PMID- 20056059
TI  - Cervicomastoidfacial versus modified facelift incision for parotid surgery: a
      patient feedback comparison.
AB  - INTRODUCTION: Traditionally, the cervicomastoidfacial (CMF) incision is used to
      excise benign tumours of the parotid gland. The rhytidectomy or modified facelift
      (MF) incision allows an alternative approach which leaves no visible neck scar.
      The objective of this study was to establish the frequency of each surgical
      approach used and identify any difference in complication and patient
      satisfaction between the two incisions for benign conditions of the parotid
      gland. PATIENTS AND METHODS: A retrospective analysis of 101 case notes for
      patients who underwent parotidectomy by both ENT and maxillofacial departments
      between January 2006 and February 2008 was undertaken. All histologically
      confirmed cases of malignancy were excluded. For each incision, immediate
      postoperative complications were obtained from the notes. A postal patient
      outcome evaluation questionnaire sought information regarding persistent and late
      complications as well as a visual analogue scar satisfaction score for both
      incisions. RESULTS: Overall, 79 parotidectomies were included (59 CMF incisions,
      20 MF incisions). Of CMF incisions, 34% suffered facial weakness immediately
      postoperatively versus 20% of MF incisions. Of CMF incisions, 4% suffered
      postoperative haematomas versus none following MF incisions. In the study cohort,
      47 (60%) responded to the postal feedback questionnaire (33 CMF versus 14 MF
      respondents). Information regarding immediate and late postoperative ipsilateral
      facial paraesthesia and gustatory sweating was obtained. Mean visual analogue
      scar satisfaction scores were 9.4 for CMF incisions and 8.9 for MF incisions.
      CONCLUSIONS: Immediate and late complications for CMF and MF approaches for
      benign disease parotidectomy were comparable, but scar satisfaction following MF
      incision was not greater than CMF incisions.

PMID- 20056060
TI  - The impact of Improving Outcomes Guidance on the management and outcomes of
      patients with carcinoma of the penis.
AB  - INTRODUCTION: The Improving Outcomes Guidance (IOG) for patients with carcinoma
      of the penis states that treatment should be provided supraregionally to
      populations of 4 million or greater who treat over 25 cases of penis cancer each
      year. This study assesses the impact of this guidance on the management and
      outcomes of patients with the disease in our region. PATIENTS AND METHODS: We
      retrospectively compared the records of 44 patients with carcinoma of the penis
      treated in our institution between 1969 and 1990 with 101 patients treated
      between 2002 and 2006, i.e. after supraregional centralisation of the service.
      RESULTS: There was no significant change in the stage or grade of the tumours.
      However, the results show that, in modern times, there was a significant increase
      in the amount of penis-preserving and nodal surgery as well as a fall in
      mortality. The improved survival is greatest in patients with poorly
      differentiated disease who may, therefore, have benefited from aggressive nodal
      surgery. CONCLUSIONS: The centralisation of surgery for carcinoma of the penis
      results in improved outcomes both in terms of penis preservation and improved
      survival and this supports the IOG guidance.

PMID- 20056061
TI  - The impact of the two-week wait rule on the diagnosis and management of bladder
      cancer in a single UK institution.
AB  - INTRODUCTION: The objective of this study was to investigate the impact of the 2
      week wait rule on patient waiting times for the diagnosis and treatment of
      bladder cancer. PATIENTS AND METHODS: Data reporting the waiting times from
      diagnosis to treatment for 100 consecutive patients newly diagnosed with bladder
      cancer immediately before and after the implementation of the 2-week wait rule
      were compared. The data were collected both prospectively and retrospectively
      from cancer multidisciplinary team meeting files and patient records. Various
      steps of the patient pathway were analysed including waiting times from referral
      to consultation as well as time to investigation and first treatment. Data were
      also analysed based upon tumour stage/grade and whether referrals were made on an
      urgent or routine basis. RESULTS: One hundred newly diagnosed patients with
      bladder cancer in each group covered a period of 4-5 years (1997-2001 and 2001
      2006). Following the introduction of the 2-week wait rule, there was a 47.6%
      reduction in the time from referral to first consultation with a specialist (42
      days vs 22 days; P < 0.001). The time between first investigation and treatment
      has not reduced significantly. We also found that, despite the introduction of
      the 2-week wait rule, only 42% of the patients were diagnosed with bladder cancer
      using this pathway. Patients referred as 'routine' waited longer to be seen in
      hospital although there was no significant delay in receiving treatment.
      CONCLUSIONS: The introduction of the 2-week wait rule has significantly reduced
      the time patients with bladder cancer wait for their first consultation with a
      specialist. However, there is no significant change in the time between first
      consultation and treatment.

PMID- 20056062
TI  - Postoperative management after loop ileostomy closure: are we keeping patients in
      hospital too long?
AB  - INTRODUCTION: Recent studies have shown that closure of loop ileostomy can be
      performed in the day-case setting, reducing the length and cost of
      hospitalisation. By analysing our patients who have undergone reversal, we aimed
      to determine the length of hospital stay and potential factors behind stays
      beyond 24 h. PATIENTS AND METHODS: A database of patients undergoing closure of
      loop ileostomy at one colorectal unit was examined. The times taken to discharge,
      morbidity and re-admission rates were recorded. RESULTS: Eighty patients
      underwent reversal of ileostomy between January 2001 and January 2006. Median age
      was 63 years (range, 22-81 years). The median length of stay was 4 days (range, 2
      32 days). The median length of stay in patients without complications was 4 days.
      Many appeared able to be discharged earlier. Seventy-two patients (90%) were able
      to tolerate a solid diet within 48 h and 54 (67.5%) had bowel function within 3
      days. Six patients went home before bowel function; none of these were re
      admitted. Twenty patients (25%) developed complications, which included wound
      infection (8%), small bowel obstruction/ileus (6%), enterocutaneous fistula (1%),
      anastomotic leak (1%), and late abdominal wall abscess (1%). Of the patients, 16%
      stayed longer than 5 days despite having no postoperative complications.
      CONCLUSIONS: The majority of patients undergoing loop ileostomy reversal at our
      institution can be discharged earlier than they are at present. Support in the
      community and the implementation of modified UK day-case surgery protocols are
      suggested to help shorten patients' length of stay.

PMID- 20056063
TI  - Emergency subtotal colectomy for fulminant Clostridium difficile colitis--is a
      surgical solution considered for all patients?
AB  - INTRODUCTION: Clostridium difficile has been an increasing problem in UK
      hospitals. At the time of this study, there was a high incidence of C. difficile
      within our trust and a number of patients developed acute fulminant colitis
      requiring subtotal colectomy. We review a series of colectomies for C. difficile,
      examining the associated morbidity and mortality and the factors that predispose
      to acute fulminant colitis. PATIENTS AND METHODS: This is a retrospective study
      of patients undergoing subtotal colectomy for C. difficile colitis in an NHS
      trust over 18 months. Case notes were reviewed for antibiotic use, duration of
      diarrhoea, treatment, blood results, preoperative imaging and surgical morbidity
      and mortality. RESULTS: A total of 1398 patients tested positive for C. difficile
      in this period. Of these, 18 (1.29%) underwent colectomy. All were emergency
      admissions, 35% medical, 35% surgical, 24% neurosurgical and 6% orthopaedic. In
      the cohort, 29% were aged less than 65 years. Patients had a median of three
      antibiotics (range, 1-6), for a median of 10 days (range, 0-59 days). Median
      length of stay prior to C. difficile diagnosis was 13 days. Subtotal colectomy
      was performed a median of 4 days (range, 0-23 days) after diagnosis.
      Postoperative mortality was 53% (9 of 17). The median C-reactive protein level
      for those who died was 302 mg/l, in contrast to 214 mg/l in the survival group.
      Whilst 62% of all C. difficile cases were medical, the colectomy rate was only
      0.7%. In the surgical specialties, the colectomy rates were 3.2% for general
      surgical, 1.2% for orthopaedic and 8% for neurosurgical patients. CONCLUSIONS:
      Colectomy for C. difficile colitis has a high mortality but can be life-saving,
      even in extremely sick patients. Although heavy antibiotic use is a predisposing
      factor, this is not an obligatory prerequisite in the development of C.
      difficile. Neither is it a disease of the elderly, making it difficult to predict
      vulnerable patients. There are large differences in colectomy rates between
      specialties and we suggest there may be a place for a surgical opinion in all
      cases of severe C. difficile colitis.

PMID- 20056064
TI  - Appendiceal faecaliths are associated with right iliac fossa pain.
AB  - INTRODUCTION: There is debate over whether a normal-looking appendix should be
      removed at diagnostic laparoscopy performed for right iliac fossa (RIF) pain.
      Faecaliths are associated with appendicitis. This study assessed whether there
      was an association between the removal of normal appendices containing faecaliths
      and improvement of symptoms. PATIENTS AND METHODS: Analysis of the histology
      database for all appendicectomies during 2003-2007 with normal histology, noting
      presence of a faecalith. Retrospective study using a telephone questionnaire for
      frequency/duration of pre-operative symptoms, postoperative symptom recurrence,
      re-admission rates and complications. The faecalith-positive (f(+)) group was
      compared to a similar control group of patients who had a normal appendix removed
      which did not contain a faecalith (f(-)). RESULTS Out of 203 appendicectomies
      performed with normal histology, 26 (13%) were f(+). Of these, 21 responded to
      the questionnaire. Thirty-one consecutive patients with normal histology and no
      faecalith were identified. A similar proportion in each group presented with
      three or more episodes of pain prior to appendicectomy (38% f(+); 39% control).
      Only one (5%) of the f(+) patients had recurring symptoms after the operation,
      compared with 14 (48%) of the control group (P = 0.0016). Only one (5%) of the
      f(+) patients underwent further investigations, compared with 11 (36%) of the
      control group (P < 0.02). None of the f(+) patients were re-admitted, compared to
      19% of the control population. There were no significant postoperative
      complications in either group. CONCLUSIONS: Appendiceal faecaliths may be a cause
      of right iliac fossa pain in the absence of obvious appendiceal inflammation. In
      this study, the policy of routine removal of a normal-looking appendix at
      laparoscopy in the absence of any other obvious pathology appeared to be an
      effective treatment for recurrent symptoms in those cases with a faecalith.
      Further studies are needed to assess this putative association.

PMID- 20056066
TI  - Changing management of suspected appendicitis in the laparoscopic era.
AB  - INTRODUCTION: The aims of this study were to examine the trends in performance of
      open and laparoscopic appendicectomy at a district general hospital, and to
      compare the diagnostic outcomes in the two patient groups. PATIENTS AND METHODS:
      Data were collected prospectively from patients undergoing an open or
      laparoscopic procedure for suspected appendicitis in an 8-year period between
      January 2000 and December 2007. RESULTS: A total of 1700 patients (873 women, 827
      men) with a median age of 24 years underwent surgery for suspected appendicitis
      in the study period. There were 1357 patients (group A) who underwent an open
      procedure for presumed appendicitis (610 women and 747 men [F:M ratio, 1:1.2]).
      There were 343 patients (group B) who underwent laparoscopy with or without
      laparoscopic appendicectomy (82 men and 261 women [F:M ratio, 1:0.31]). Over the
      study period, there was an increasing trend towards the performance of
      laparoscopic procedures for suspected appendicitis, increasing from 4% to 39% of
      the total per year. In group A, 1172 (86%) patients had appendicular pathology,
      while the appendix was normal histologically in 178 (13%). Other pathologies were
      diagnosed intra-operatively in 1%. In group B, 193 patients (56%) had
      appendicular pathology while in 150 (44%) the appendix was normal. In the
      subgroup with a normal appendix, 56 patients (37%) had another cause for their
      symptoms identified. CONCLUSIONS: Laparoscopic appendicectomy is increasingly
      being performed. Laparoscopy is often used as a diagnostic tool in general
      surgical patients, particularly women, with lower abdominal pain. In effect,
      these patients are undergoing diagnostic laparoscopy, with or without
      appendicectomy. This has resulted in a lower positive appendicectomy rate, but a
      higher yield of diagnoses other than appendicitis, in the laparoscopic group.
      Overall appendicectomy rates, however, have remained unchanged.

PMID- 20056068
TI  - A comparison of digital and manual templating using PACS images.

PMID- 20056069
TI  - Comment on: Stapled transanal resection of the rectum (STARR) for obstructed
      defaecation syndrome.

PMID- 20056070
TI  - Lack of cost analysis.

PMID- 20056071
TI  - Improving clinical coding accuracy.

PMID- 20056072
TI  - Changing practice from conventional surgery to endovenous treatments produces
      excellent results for both long and short saphenous varicose veins.

PMID- 20056073
TI  - Improving access to expedited carotid endarterectomy.

PMID- 20056074
TI  - Clostridium difficile infection: more known than is realised.

PMID- 20056075
TI  - Treatment of ischaemic steal syndrome resulting from vascular access surgery.

PMID- 20056076
TI  - [Generation and preliminary functional study of a CD133-2-harboring L929 cell
      line].
AB  - AIM: To generate an engineered L929 cell line harboring human CD133-2 and perform
      the functional study of the gene-modified cell line. METHODS: The human CD133-2
      gene was obtained by PCR from a cDNA library of foetus liver. After digested with
      Hind III and BamH I, the PCR product was cloned into pIRES2-EGFP vector. The
      recombinant plasmid CD133-2/pIRES2-EGFP was transfected into L929 cell line using
      lipofectamine, followed by G418 selection. RT-PCR, Western blot and flow
      cytometry (FCM) were used to detect the expression of CD133-2. MTT was used to
      analyze the effect of the CD133-2/L929 cells on proliferation of T cells. FCM was
      performed to monitor T cell activation by detecting T cell surface markers of
      CD4CD25 and CD8CD25 after T cells were cocultured with the CD133-2/L929 cells in
      the presence of an anti-CD3 mAb. RESULTS: A stable cell line constitutively
      expressing the human CD133-2 was established successfully. In the presence of the
      anti-CD3 mAb, CD133-2/L929 cells caused inhibition of T cell proliferation and
      down-regulation of the activation markers of CD4CD25 and CD8CD25 on T cells.
      CONCLUSION: The engineered CD133-2/L929 cell line provides a gain-of-function
      cell model for further understanding the biological role of CD133-2.

PMID- 20056077
TI  - [Expression and functional analysis of transcriptional factor JunB in hepatic
      cancer cells].
AB  - AIM: To construct the eukaryotic expression vector harboring transcriptional
      factor JunB and to observe the expression, localization and biological function
      of JunB in hepatic cancer cells. METHODS: The JunB gene was amplified by PCR from
      the human liver tissue cDNA library. After confirmed by DNA sequencing in the T
      vector, the JunB gene was subcloned into pcDNA3.1(-) and pEGFP-C3 vectors,
      respectively. The recombinant vectors pcDNA-JunB and pEGFP-JunB were confirmed by
      Kpn I and BamH I restriction enzyme digestion. The recombinant vectors were
      transiently transfected into the hepatic cancer cells HepG2 using
      Lipofectamin2000. Western blotting was used to detect the expression of exogenous
      JunB and fluorescence microscopy was applied to observe the localization of JunB
      protein coupled with enhanced green fluorescent protein (EGFP) in hepatic cancer
      cells. Double luciferase reporter assay was performed to determine the effect of
      JunB on the transcriptional regulation of target genes. RESULTS: The recombinant
      eukaryotic expression vector carrying JunB or JunB-EGFP fusion gene was
      constructed and transiently transfected into HepG2 cells. Western blot analysis
      confirmed the exogenous expression of JunB. JunB-EGFP was observed uniquely in
      the nuclei. Double luciferase assay showed the transcriptional up-regulation of
      the VEGF in the presence of JunB. CONCLUSION: We constructed the recombinant
      eukaryotic expression vectors harboring JunB and JunB-EGFP successfully. The
      exogenous JunB is localized in the nuclei of transiently transfected HepG2 cells,
      suggesting JunB may function as a transcriptional factor. The result of reporter
      assay showed that JunB up-regulates the expression of VEGF, a tumor-angiogenesis
      associated molecule, at a transcriptional level. These demonstrate that JunB
      might be a novel target for an anti-angiogenesis treatment for hepatic cancers.

PMID- 20056078
TI  - [Effect of inducible nitric oxide synthase on pancreas islet apoptosis in rats].
AB  - AIM: To investigate the effect and mechanism of cytokine and inducible nitric
      oxide synthase on apoptosis and function of rat pancreas islets cultured in
      vitro. METHODS: Islets from Wistar rats were cultured in vitro and divided
      randomly into four groups: blank control group, cytokine group of islets cultured
      with TNF-alpha+IL-1beta, aminoguanidine (AG) group of islets cultured with
      aminoguanidine, and AG + cytokine group of islets cultured with TNF-alpha+IL
      1beta and aminoguanidine. The nutrient fluid nitric oxide level and islets
      cNOS/iNOS activity were detected by test kit and the expressions of iNOS mRNA and
      apoptosis related gene (Bax, Bcl-2) were evaluated by RT-PCR. The viability of
      the islets was examined by AO/EB staining and the function of the islets was
      detected by insulin secretion index assay. RESULTS: After co-cultured with
      cytokines IL-1beta and TNF-alpha, the expression and activity of iNOS in islet
      tissues enhanced (38.93+/-4.72) U/mL and the concentration of NO in medium
      increased remarkably(313.0+/-35.4) mol/L.The survival rate of cells and the
      insulin secretion index decreased with the up-regulation of proapoptosis gene and
      down-regulation of anti-apoptosis gene. But the activity of cNOS remained
      unchanged. Aminoguanidine reduced the cell apoptosis and increased the survival
      rate and insulin secretion index, and the activity of iNOS was inhibited.
      CONCLUSION: iNOS plays an important role in the apoptosis of islets cultured by
      cytokines TNF-alpha and IL1-beta. Aminoguanidine prevents the islets from the
      damage of iNOS, alleviates the impairment of cytokines to islets, lessens the
      cell apoptosis and ameliorates the survival and function of islets.

PMID- 20056079
TI  - [Impact of novel negative immunoregulatory dendritic cells on regulatory T cells
      in cardiac allograft recipient rats].
AB  - AIM: To investigate the effect of recipient dendritic cells (DC) loaded with PUVA
      treated donor splenic lymphocytes (PUVA-SP) on CD4(+) CD25(+) regulatory T cells
      (Treg) and the survival time of cardiac allograft in rats. METHODS: Cardiac
      allografts from DA donor rats were transplanted into LEW recipient rats. Donor
      splenic lymphocytes were treated with 8-methoxypsoralen plus UVA irradiation
      (PUVA). Recipient bone marrow-derived DCs were co-cultured with PUVA-treated
      donor splenic lymphocytes (PUVA-SP) and the phenotype of the treated DCs was
      analyzed with flow cytometry. Seven days before transplantation, recipients were
      given infusion of recipient DCs loaded with PUVA-treated donor splenic
      lymphocytes (PUVA-SP DC) through the peripheral vein. The cardiac allograft
      survival time was evaluated by palpation every day. The frequency of
      CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells and their Foxp3 expression
      were analyzed using flow cytometry. Fourteen days after transplantation, T
      lymphocytes of the recipient rats receiving PUVA-SP DC were transferred to the
      normal LEW rats. The delayed type hypersensitivity (DTH) of the transferred LEW
      rats to the donor DA rats antigen then was measured. RESULTS: After co-cultured
      with PUVA-SP, recipient DCs still maintained an immature phenotype with low
      levels of MHC II, CD80 and CD86. The injection of PUVA-SP DCs significantly
      increased the frequencies of CD4(+)CD25(+) T cells and CD4(+) CD25(high) T cells
      and the expression of Foxp3 in the peripheral blood, and prolonged the allograft
      survival time. The donor antigen specific hyporesponsiveness could be transferred
      to normal LEW rats through adoptive transfusion. CONCLUSION: PUVA-SP DCs
      effectively up-regulate CD4(+) CD25(+) Foxp3(+) Treg and induce donor antigen
      specific hyporesponsiveness, thus prolonging the allograft survival time.

PMID- 20056080
TI  - [Recombinant adeno-associated virus serotype 9 transfection of rats H9C2 cells in
      vitro].
AB  - AIM: To evaluate the transfection efficiency using recombinant adeno-associated
      virus Serotype 9 mediated enhanced green fluorescent protein (rAAV9- EGFP) to
      rats H9C2 cells and the impact on growth of H9C2 cells. METHODS: rAAV9-EGFP was
      transfected into H9C2 cells at different multiplicities of infection (MOI=1 x
      10(5), 1 x 10(6), 1 x 10(7)). EGFP expression in the cells was observed under
      inverted fluorescence microscope, and the EGFP-positive cell percentage
      determined by flow cytometry. Alamar Blue assay was used to assess the
      proliferation of the transfected cells. RESULTS: The cells with rAAV9-EGFP
      transfection at MOI of 1 x 10(6) and 1 x 10(7) began to exhibit EGFP expression 1
      days after transfection and the cells transfection at MOI of 1 x 10(5) began to
      exhibit EGFP expression 2 days after transfection. the fluorescence intensity
      increased with the MOI used for transfection. EGFP expression reached the maximum
      on day 4, at the point of which the transduction efficiency of rAAV9-EGFP in H9C2
      cells was (14.1+/-0.2)%, (35.1+/-4.8)% and (56.8+/-0.1)%. Corresponding to MOIs
      of 1 x 10(5), 1 x 10(6) and 1 x 10(7), respectively. Alamar Blue assay did not
      reveal significant difference in the absorbance between the transfected cells and
      the control cells after transfection. CONCLUSION: rAAV9-EGFP gene can be stably
      and efficiently expressed in H9C2 cells without causing cell growth
      inhibition.This study played foundation for further research.

PMID- 20056081
TI  - [Relationship of IL-6 and IL-8 secretion in epithelial ovarian cancer cell lines
      with their sensitivity to tamoxifen as well as MAPK, Akt and estrogen receptor
      phosphorylation].
AB  - AIM: To investigate the relationship of IL-6 and IL-8 secretion in four
      epithelial ovarian cancer cell lines (A2780, CAOV-3, SKOV-3 and ES-2) with their
      sensitivity to tamoxifen (TAM) as well as MAPK, Akt and estrogen receptor (ER)
      phosphorylation, and to explore the mechanism of endocrine therapy resistance
      caused by IL-6 and IL-8 in ovarian cancer cells. METHODS: Reverse transcription
      polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA)
      were performed to analyze the expression of IL-6 and IL-8. MTT assay was carried
      out to examine the response of ovarian cancer cells to TAM. Western blot was used
      to detect phosphorylated MAPK, Akt and ER. RESULTS: Except A2780 cells, three
      other ovarian cancer cells constitutively expressed IL-6 and IL-8. The mRNA
      levels of IL-6 and IL-8 correlated with their protein levels in four ovarian
      cancer cells. The four ovarian cancer cells showed different response to TAM.
      A2780 cells was the most responsive, whereas CAOV-3, SKOV-3 and ES-2 cells were
      TAM-resistant to a different degree. There was a notable difference in
      phosphorylated MAPK, Akt and ER (serine 118 and 167) among the four ovarian
      cancer cells. CONCLUSION: Autocrine production of IL-6 and IL-8 in epithelial
      ovarian cancer cell lines is inversely associated with cell response to TAM, and
      positively associated with phosphorylated MAPK, Akt and ER.

PMID- 20056082
TI  - [Analysis on the relationship between p57 and cholesterol in cellular membrane].
AB  - AIM: To investigate the relationship between p57 and cholesterol in cellular
      membrane under physiological conditions. METHODS: Different concentrations of
      mbetaCD were used to extract cholesterol from cellular membrane of U937 cells.
      The cellular membrane was prepared by ultracentrifugation and the content change
      of p57 in cellular membrane component was measured by Western blot analysis.
      Discontinuous sucrose density gradient centrifugation was used to prepare lipid
      rafts and the content of p57 in them was measured by Western blot analysis.
      RESULTS: The degradation of cholesterol level in cellular membrane didn't lead to
      obvious content change of p57 in cellular membrane component. Furthermore, no p57
      protein was found in lipid rafts. CONCLUSION: No relationship between p57 and
      cholesterol in cellular membrane was found in the physiological condition, which
      is obviously different from that in pathological condition caused by the invasion
      of pathogenic mycobacteria.

PMID- 20056083
TI  - [Immune response in BALB/c mice immunized with BCG expressing HBV truncated C
      gene and preS1 gene].
AB  - AIM: To study expressing of HBV truncated core and preS1 protein in BCG and to
      explore the effect of humoral and cellular immune response stimulated by the
      recombinant BCG. METHODS: A shuttle vector was constructed and was transformed
      into BCG which including truncated Core gene and preS1 gene of HBV. The
      recombinant BCGs were analyzed with SDS-PAGE and Western blot. The three groups
      of BALB/c mice were immunized with saline, BCG, BCG-pDE22 and BCG-pDE22-CS1
      respectively. Then the antibody titer and CTL effects were evaluated. RESULTS:
      Compared with the control group, the recombinant BCG could express a new protein
      band of 24 kD which was consistent with the size of CS1 fused protein which
      displayed a good antigen-binding property by Western blot analysis. The antibody
      titer significantly increased and CTL effect apparently enhanced in the
      recombinant BCG immunized group. CONCLUSION: BCG could be as live vector which
      carrying HBV related genes, which developing a novel vaccine against HBV.

PMID- 20056084
TI  - [Role of transcription factor T-bet and Eomes in IFN-gamma secretion of different
      human T cell subsets].
AB  - AIM: To investigate the effect of siRNAs specific for T-bet and Eomesodermin
      (Eomes) in interferon-gamma (IFN-gamma) production of different human T cell
      subsets. METHODS: Double-stranded small interfering RNA (siRNA) sequences
      specific for genes of T-bet and Eomes were chemically synthesized and transfected
      into anti-CD3 mAb activated alphabeta T cells and Mtb-Ag activated gammadelta T
      cells. CD4(+), CD8(+) T and gammadelta T cells were sorted by flow cytometry and
      the expressions of T-bet and Eomes gene mRNA were detected by RT-PCR technique.
      The changes of IFN-gamma production were determined by flow cytometry. RESULTS:
      After two series of transfection, the siRNA-FAM(+) cells were about 50% in the
      transfected cells. The IFN-gamma(+) cells in CD4(+) T cells (50.20%) decreased in
      the cells transfected with T-bet siRNA (18.46%) but no obvious decrease was
      observed in the cells transfected with Eomes siRNA, whereas the IFN-gamma(+)
      cells in CD8(+) T cells (76.51%) decreased in the cells transfected with Eomes
      siRNA (25.37%) and no obvious decrease was observed in the cells transfected with
      T-bet siRNA. However, the IFN-gamma producing cells in gammadelta T cells
      (76.52%) decreased in the cells transfected with T-bet siRNA (56.57%) or with
      Eomes siRNA (42.53%). CONCLUSION: At the level of transcription factors, T-bet
      and Eomes are important transcription factors for the regulation of IFN-gamma
      production in CD4(+) and CD8(+) T cells, respectively. Both T-bet and Eomes may
      simultaneously be involved in the regulation of the IFN-gamma production of
      gammadeltaT cells.

PMID- 20056085
TI  - [N-acetylcysteine antagonizes the Interleukin-18-induced expression of TNF-alpha
      and IL-6 in mouse vascular smooth muscle cells].
AB  - AIM: To explore the effect of N-acetylcysteine(NAC)on the interleukin(IL)18
      induced expression of tumor necrosis factor (TNF) alpha and interleukin(IL) 6 in
      mouse vascular smooth muscle cells(VSMC). METHODS: VSMC was stimulated with
      various concentrations of IL-18 for different times after addition of NAC(5
      mmol/L) for 1 h. The messenger ribonucleic acid(mRNA) expression of TNF-alpha and
      IL-6 was measured by RT-PCR and the protein secretion of the two cytokines was
      determined by ELISA method. Western blot was used to analyze the activation of NF
      kappaB in VSMC. RESULTS: IL-18 significantly increased the mRNA expression and
      protein secretion of TNF-alpha and IL-6 (P>0.01) in a dose-dependent and a time
      dependent ways. NAC inhibited the mRNA expression and protein secretion of TNF
      alpha and IL-6 induced by IL-18(P>0.01). Western blot results showed the NAC
      inhibited the IL-18-induced activation of NF-kappaB in VSMC. CONCLUSION: N
      acetylcysteine antagonizes the production of TNF-alpha and IL-6 induced by IL-18
      in VSMC.

PMID- 20056086
TI  - [Computer-aided-designing and eukaryotic expression of recombinant HPV 16
      vcaccine].
AB  - AIM: To develop a recombinant protein vaccine with epitopes on L1 protein for
      prevention of HPV16 infection. METHODS: One B cell epitope and one T cell epitope
      from HPV16 L1 protein were chosen to construct genes encoding different
      recombinant proteins. Then all the 3D structures of the proteins were predicted
      by Geno3D in internet. An optimal protein named RH was chosen in which three B
      epitopes' location simulates that in the real HPV16 L1. Gene X (consisting of
      B+T+T) and gene Y (consisting of B+T) were constructed by multiple PCR. RH gene
      (consisting of X+X+X+X+Y+Y+Y) was constructed, sub-cloned into pFastbac1, and
      expressed in Sf9. RESULTS: RH protein with epitopes on HPV16 L1 was designed and
      predicted by Geno3D. RH gene was constructed and sub cloned into pFastbac1.
      Finally, it was successfully expressed in baculovirus expression system.
      CONCLUSION: A HPV16 recombinant vaccine is successfully constructed and
      expressed.

PMID- 20056087
TI  - [Cloning and expression of human keratin 8 gene cDNA in E.coli].
AB  - AIM: To clone and express human keratin 8 gene cDNA in E.coli. METHODS: Human
      cytokeratin 8 gene cDNA was amplified by RT-PCR from genomic RNA of human cell
      line 7721. The amplified cytokeratin 8 gene cDNA was cloned into pMD18-T vector.
      Then, the CK8 cDNA was amplified by PCR from recombinant plasmid pMD18-CK8, and
      was subcloned into pET-28a(+) expression vector. The recombinant plasmid pET-28a
      CK8 DNA was transformed into E.coli DH5alpha strain. RESULTS: Human cytokeratin 8
      gene cDNA was cloned, and the recombinant plasmid pMD18-CK8 was transformed into
      E.coli. The CK8 cDNA was subcloned into E.coli DH5alpha strain, and successfully
      expressed in E.coli. CONCLUSION: Human cytokeratin 8 gene cDNA is cloned, and
      successfully expressed in E.coli, which lay the foundation of further study on
      the CK8 biological properties and functions.

PMID- 20056088
TI  - [HIV-1 Nef regulates ICAM-1 expression on endothelial cells via Erk /Mapk
      signaling pathway].
AB  - AIM: To explore the effect of HIV-1 Nef on the ICAM-1 expression of endothelial
      cells ECV-304 and its signaling pathways. METHODS: ICAM-1 expression on the
      endothelial cells ECV-304 was detected by Western blot and FCM assay. Kinase
      inhibitor PD98059 was used in the cells to analyze the ERK signaling pathway.
      RESULTS: Western blot showed that ICAM-1 and p-ERK protein expression increased
      in Nef expressed ECV304 cells (ECV304-Nef) and FCM results showed that the
      percentage of ICAM-1 positive cells in ECV304-Nef and control cells was (35.3+/
      2.2)% and (12.5+/-0.8)% respectively (P>0.01). p-ERK inhibitor PD98059 almost
      completely blocked the Nef up-regulation of the p-ERK and ICAM-1. When p-ERK
      inhibitor was added, the percentage of ICAM-1 positive cells in ECV304-Nef
      (11.4+/-1.1)% was reduced to the level of the control cells (10.4+/-1.5)%
      (P>0.05). CONCLUSION: Erk/Mapk signaling pathway may contribute to the over
      expression of adhesion molecules ICAM-1 gene in HIV-1 Nef positive cells. These
      findings may provide the basis for further research on the mechanism and
      treatment of HIV-1 infection.

PMID- 20056089
TI  - [Preparation, characterization and potential application of monoclonal antibody
      18A4 against AGR2].
AB  - AIM: To prepare mouse monoclonal antibodies (mAb) against AGR2 (human homolog of
      xenopus anterior gradient 2), to characterize these antibodies' properties, and
      to develop potential applications. METHODS: BALB/c mice were immunized with AGR2
      MBP (maltose binding protein) fusion protein. The mAb was prepared by hybridoma
      technique and purified by protein G affinity chromatography. The titer and
      specificity of the mAb was determined by ELISA and Western blot respectively. The
      mAb was then further characterized by immunoprecipitation, immunofluorescent
      staining and tumor cell inhibition assay. RESULTS: One clone of hybridoma, 18A4,
      secreting specific mAb against AGR2, was obtained. The Ig subclass of the mAb was
      IgG1 (kappa). The titer of the mAb was 1 x 10(-6);. Western blot analysis showed
      specific binding of 18A4 with both recombinant and native AGR2 in cell extract.
      Immunofluorescent staining using 18A4 mAb demonstrated specific staining of AGR2
      in the cytoplasma of Breast cancer cell line MCF7. Immunoprecipitation assay
      confirmed that this mAb could specifically bind and effectively precipitate the
      native AGR2. mAb 18A4 could also inhibit the growth of breast cancer cell MCF7.
      CONCLUSION: The mAb anti-AGR2 with high titer and specificity has been obtained.
      This mAb, 18A4, can be used in most molecular biology studies including Western
      blot, immunostaining, immunoprecipitation. It also inhibited the growth of cancer
      cells and therefore is a potential therapeutic starting point. It is a useful
      tool for the functional study of AGR2 and for the diagnosis and potential
      treatment of certain cancers.

PMID- 20056090
TI  - [Preparation and selection of the monoclonal antibody used for kits to detect
      BNP32 which was applied to clinical research].
AB  - AIM: To prepare the monoclonal antibody (mAb) used for kits to detect the BNP32
      antigen by means of double-antibody sandwich ELISA assay. Comparasion differences
      on detection BNP between double-antibody sandwich ELISA and Roche ECL. METHODS:
      BALB/c mice were immunized with purified recombinant BNP32 protein and by routine
      hybridoma technique, Then comparasion differences on detection BNP between double
      antibody sandwich ELISA and Roche ECL. RESULTS: 16 hybridoma cell lines secreting
      potent mAb against BNP32 were obtained. The subtype of these 16 mAb were found to
      be IgG1, IgG2a and IgM, then their cross-blocking properties were analyzed, when
      they reacted with the BNP32 protein in direct ELISA in order to offer the
      valuable data for selecting feasible pair of mAb in the detection of the BNP32
      antigen. All the mAbs were used for the detection of BNP32 by double-antibody
      sandwich ELISA. In addition, the mAbs were purified and HRP-labelled in advance.
      Finally, we had successfully screened a pair of mAbs, which exhibited a
      sensitivity of 20 ng/L for the detection of BNP32 antigen. The two detection
      methods have very good consistency (kappa=0.828>0.75)between double-antibody
      sandwich ELISA and Roche ECL. There was no statistics significance on differences
      between these two methods(P>0.05). CONCLUSION: It is evident that this pair of
      mAb shows excellent detection of BNP32. The double-antibody sandwich ELISA can be
      good apply to detect BNP level in clinical congestive heart failure patients.

PMID- 20056091
TI  - [Relationship between the level of MCP-1 expression in sera of RA patients and
      ILD].
AB  - AIM: To investigate the function and clinical significance of monocyte
      chemoattractant protein-1 MCP-1 in the pathogenesis of rheumatoid
      arthritis(RA)and the relation ship between the expression of MCP-1 in serum and
      interstitial lung disease (ILD) secondary from RA. METHODS: 60 patients with RA
      were divided into two groups: 30 cases with simple RA group and 30 cases with ILD
      secondary from RA (RA+ILD group). The control group incuided 20 healthy cases.
      Enzyme linked immunosorbent assay (ELISA ) was used to determine the serum
      expression of MCP-1 in patients healthy controls. The differences of MCP-1 level
      and other laboratory indexes (IgG, IgA, IgM, alpha2-G, gamma-G, RF, ESR, CRP, and
      the number of arthrocele) in different groups were compared with software
      spss13.0. RESULTS: The expression of MCP-1 in simple RA patients was
      significantly higher than that in the control group (P>0.05) and significantly
      lower than that in the RA+ILD group (P>0.01). The level of MCP-1 in serum of RA
      patieuts was positively correlated with IgG, IgM, and gamma-G. CONCLUSION: MCP-1
      plays an important role in the pathogenesis of RA and may contribute to the
      promotion of lung fibrosis in ILD secondary from RA.

PMID- 20056092
TI  - [Ethnic disparity in health among pregnant women and infants].

PMID- 20056093
TI  - [Minimally invasive surgery for hyperparathyroidism].
AB  - INTRODUCTION: The traditional surgical approach for primary hyperparathyroidism
      (PHPT) involves a bilateral neck exploration to identify all parathyroid glands
      and remove the suspected pathological parathyroid gland(s). However, with
      improved preoperative imaging modalities and the use of perioperative measuring
      of PTH the unilateral minimal invasive approach has been introduced. The purpose
      of this study was to describe the results of minimal invasive parathyroidectomy.
      MATERIAL AND METHODS: A total of 116 consecutive patients underwent PHPT surgery
      (117 procedures) with a minimal invasive approach. RESULTS: A true positive
      sestamibi scintigraphy was found in 75 of 116 (65%) cases. A total of 80 patients
      (69%) underwent a unilateral surgical procedure and 56 patients (48%) minimally
      invasive surgery. In 113 of 117 procedures one or more pathological parathyroid
      glands were found. The median duration of the surgical procedure was 55 minutes
      and only 35 minutes for the minimal invasive approach. No permanent vocal cord
      paralysis was found. In two patients, persistent mild hypercalcaemia was
      encountered postoperatively and in a further patient recurrence was seen one year
      after. CONCLUSION: In our hands the success rate for focused minimal invasive
      surgery for the treatment of PHPT is equal to or better than results obtained by
      the traditional bilateral neck exploration. The minimally invasive approach is a
      less time-consuming and safe procedure with a low complication rate.
      Postoperative hypocalcaemia is rare and further advantages include improved
      cosmetic results and reduced surgical trauma.

PMID- 20056094
TI  - [Systemic prokinetic treatment of postoperative ileus following abdominal
      surgery. Assessment of a Cochrane review].
AB  - Based on the evidence presented in the Cochrane review "Systemic prokinetic
      pharmacologic treatment for postoperative adynamic ileus following abdominal
      surgery in adults", routine administration of systemic prokinetics for the
      prevention of postoperative ileus is not recommendable. The potential of
      selective opioid antagonists and intravenous lidocaine should be further
      investigated, particularly in conjunction with laparoscopic surgery, epidural
      pain management and fast-track surgery.

PMID- 20056095
TI  - [Monitoring of bioavailability, pharmacokinetics and immunogenicity of tumour
      necrosis factor-alpha inhibitors].
AB  - Treatment of inflammatory bowel disease (IBD) with antibodies against tumour
      necrosis factor-alpha (TNF) is effective. Not all patients respond, however, and
      the effect wears off in a considerable fraction of initial responders over time.
      Individual differences in bioavailability, pharmacokinetics and immunogenicity
      are now recognized as essential problems in the use of biologicals, and blood
      measurements of functional anti-TNF antibodies and antibodies against anti-TNF
      drugs with robust and clinically relevant methods may optimize treatment of IBD
      through individualized therapeutic regimens.

PMID- 20056096
TI  - [Cardiotoxicity induced by 5-fluorouracil or capecitabine].
AB  - 5-fluorouracil and capecitabine have significant antineoplastic activity towards
      various solid tumors. Cardiotoxicity causing angina, arrhythmia and infarction
      are serious adverse events associated with these agents. The pathogenesis is
      discussed and symptoms of cardiotoxicity, intervention with nitroglycerine and
      risk factors as cardiac comorbidity are described. Following cardiotoxicity, lack
      of alternative active agents may provide grounds to rechallenge with 5-FU. In
      this situation, dose-modified 5-FU-based chemotherapy supported by medical
      antiangina prevention is feasible.

PMID- 20056097
TI  - [Vision jeopardizing xerophthalmia in Denmark].
AB  - A 54-year-old alcoholic was admitted with keratomalacia in 2001. The right cornea
      had an ulceration and the left cornea had stromal necrosis and a perforation.
      Serum retinol and serum betacaroten were extremely low. Treatment consisted of
      high-dose retinol and left sided cornea transplantation. The right eye healed
      with little scarring, vision: 0.5. The left eye was stabilized after a second
      cornea transplantation and covering with conjunctiva, vision: hand movement at a
      distance of 1 m. This proves the existence of symptomatic vitamin A deficiency
      among socially exposed subjects in Denmark.

PMID- 20056098
TI  - [Hemophagocytosis associated with cytomegalovirus infection and azathioprine
      treatment for inflammatory bowel disease].
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by
      fever and cytopenia due to phagocytosis of erythrocytes, leukocytes, platelets,
      and their precursors in bone marrow and other tissues. HLH can be primary
      (genetic) or associated with neoplastic diseases, autoimmune diseases or
      infections. HLH is a rare syndrome but can cause very severe illness, and if
      unrecognized/untreated the condition is associated with a high mortality. We
      present two cases of cytomegalovirus infection-associated HLH in patients with
      inflammatory bowel disease during azathioprin treatment.

PMID- 20056099
TI  - [An adult case of haemophilus parainfluenzae bacteremia and meningitis].
AB  - A case of bacteremia and meningitis caused by Haemophilus parainfluenzae in an
      adult patient without known immunodeficiency and normal complement system is
      presented. H. parainfluenzae has not previously been reported as the cause of
      meningitis in Denmark. Patients with invasive H. parainfluenzae infection should
      be examined for complement factor 7 defect.

PMID- 20056100
TI  - An aptamer-based fluorescent biosensor for potassium ion detection using a pyrene
      labeled molecular beacon.
AB  - A novel and sensitive biosensor based on aptamer and pyrene-labeled fluorescent
      probes for the determination of K+ was developed. The aptamer was used as a
      molecular recognition element and a partially complementary oligonucleotide with
      the aptamer was labeled by pyrene moieties at both ends to transduce the binding
      event of K+ with aptamer. In the presence of K+, the complementary
      oligonucleotides were displaced from aptamers, which was accompanied by excimer
      fluorescence of pyrenes because the self-hairpin structure of the complementary
      oligonucleotide brought pyrene moieties into close proximity. However, it gave
      only monomer emission in the absence of K+. Under optimum conditions, the
      relative fluorescence intensity of pyrene was proportional to the concentration
      of K+ in the range of 6.0 x 10(-4) to 2.0 x 10(-2) M. A detection limit of 4.0 x
      10(-4) M was achieved. Moreover, this method was able to detect K+ with high
      selectivity in the presence of Na+, NH4+, Mg2+, and Ca2+ ions of biological
      fluids. In brief, the assay may have great potential applications, especially in
      a biological environment because of its simplicity, sensitivity, and specificity.

PMID- 20056101
TI  - Purification and kinetic characterization of recombinant alternative oxidase from
      Trypanosoma brucei brucei.
AB  - The trypanosome alternative oxidase (TAO) functions in the African trypanosomes
      as a cytochrome-independent terminal oxidase, which is essential for their
      survival in the mammalian host and as it does not exist in the mammalian host is
      considered to be a promising drug target for the treatment of trypanosomiasis. In
      the present study, recombinant TAO (rTAO) overexpressed in a haem-deficient
      Escherichia coli strain has been solubilized from E. coli membranes and purified
      to homogeneity in a stable and highly active form. Analysis of bound iron
      detected by inductively coupled plasma-mass spectrometer (ICP-MS) reveals a
      stoichiometry of two bound iron atoms per monomer of rTAO. Confirmation that the
      rTAO was indeed a diiron protein was obtained by EPR analysis which revealed a
      signal, in the reduced forms of rTAO, with a g-value of 15. The kinetics of
      ubiquiol-1 oxidation by purified rTAO showed typical Michaelis-Menten kinetics
      (K(m) of 338microM and V(max) of 601micromol/min/mg), whereas ubiquinol-2
      oxidation showed unusual substrate inhibition. The specific inhibitor,
      ascofuranone, inhibited the enzyme in a mixed-type inhibition manner with respect
      to ubiquinol-1.

PMID- 20056102
TI  - Sodium-translocating NADH:quinone oxidoreductase as a redox-driven ion pump.
AB  - The Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) is a component of
      the respiratory chain of various bacteria. This enzyme is an analogous but not
      homologous counterpart of mitochondrial Complex I. Na+-NQR drives the same
      chemistry and also uses released energy to translocate ions across the membrane,
      but it pumps Na+ instead of H+. Most likely the mechanism of sodium pumping is
      quite different from that of proton pumping (for example, it could not
      accommodate the Grotthuss mechanism of ion movement); this is why the enzyme
      structure, subunits and prosthetic groups are completely special. This review
      summarizes modern knowledge on the structural and catalytic properties of
      bacterial Na+-translocating NADH:quinone oxidoreductases. The sequence of
      electron transfer through the enzyme cofactors and thermodynamic properties of
      those cofactors is discussed. The resolution of the intermediates of the
      catalytic cycle and localization of sodium-dependent steps are combined in a
      possible molecular mechanism of sodium transfer by the enzyme.

PMID- 20056103
TI  - Consequences of the pathogenic T9176C mutation of human mitochondrial DNA on
      yeast mitochondrial ATP synthase.
AB  - Several human neurological disorders have been associated with various mutations
      affecting mitochondrial enzymes involved in cellular ATP production. One of these
      mutations, T9176C in the mitochondrial DNA (mtDNA), changes a highly conserved
      leucine residue into proline at position 217 of the mitochondrially encoded Atp6p
      (or a) subunit of the F1FO-ATP synthase. The consequences of this mutation on the
      mitochondrial ATP synthase are still poorly defined. To gain insight into the
      primary pathogenic mechanisms induced by T9176C, we have investigated the
      consequences of this mutation on the ATP synthase of yeast where Atp6p is also
      encoded by the mtDNA. In vitro, yeast atp6-T9176C mitochondria showed a 30%
      decrease in the rate of ATP synthesis. When forcing the F1FO complex to work in
      the reverse mode, i.e. F1-catalyzed hydrolysis of ATP coupled to proton transport
      out of the mitochondrial matrix, the mutant showed a normal proton-pumping
      activity and this activity was fully sensitive to oligomycin, an inhibitor of the
      ATP synthase proton channel. However, under conditions of maximal ATP hydrolytic
      activity, using non-osmotically protected mitochondria, the mutant ATPase
      activity was less efficiently inhibited by oligomycin (60% inhibition versus 85%
      for the wild type control). Blue Native Polyacrylamide Gel Electrophoresis
      analyses revealed that atp6-T9176C yeast accumulated rather good levels of fully
      assembled ATP synthase complexes. However, a number of sub-complexes (F1, Atp9p
      ring, unassembled alpha-F1 subunits) could be detected as well, presumably
      because of a decreased stability of Atp6p within the ATP synthase. Although the
      oxidative phosphorylation capacity was reduced in atp6-T9176C yeast, the number
      of ATP molecules synthesized per electron transferred to oxygen was similar
      compared with wild type yeast. It can therefore be inferred that the coupling
      efficiency within the ATP synthase was mostly unaffected and that the T9176C
      mutation did not increase the proton permeability of the mitochondrial inner
      membrane.

PMID- 20056104
TI  - Differential mechanism of light-induced and oxygen-dependent restoration of the
      high-potential form of cytochrome b(559) in Tris-treated photosystem II
      membranes.
AB  - The effect of illumination and molecular oxygen on the redox and the redox
      potential changes of cytochrome b(559) (cyt b(559)) has been studied in Tris
      treated spinach photosystem II (PSII) membranes. It has been demonstrated that
      the illumination of Tris-treated PSII membranes induced the conversion of the
      intermediate-potential (IP) to the reduced high-potential (HP(Fe2+)) form of cyt
      b(559), whereas the removal of molecular oxygen resulted in the conversion of the
      IP form to the oxidized high-potential (HP(Fe3+)) form of cyt b(559). Light
      induced conversion of cyt b(559) from the IP to the HP form was completely
      inhibited above pH 8 or by the modification of histidine ligand that prevents its
      protonation. Interestingly, no effect of high pH or histidine modification was
      observed during the conversion of the IP to the HP form of cyt b(559) after the
      removal of molecular oxygen. These results indicate that conversion from the IP
      to the HP form of cyt b(559) proceeds via different mechanisms. Under
      illumination, conversion of the IP to the HP form of cyt b(559) depends primarily
      on the protonation of the histidine residue, whereas under anaerobic conditions,
      the conversion of the IP to the HP form of cyt b(559) is driven by higher
      hydrophobicity of the environment around the heme iron resulting from the absence
      of molecular oxygen.

PMID- 20056105
TI  - Maintenance and expression of the S. cerevisiae mitochondrial genome--from
      genetics to evolution and systems biology.
AB  - As a legacy of their endosymbiotic eubacterial origin, mitochondria possess a
      residual genome, encoding only a few proteins and dependent on a variety of
      factors encoded by the nuclear genome for its maintenance and expression. As a
      facultative anaerobe with well understood genetics and molecular biology,
      Saccharomyces cerevisiae is the model system of choice for studying nucleo
      mitochondrial genetic interactions. Maintenance of the mitochondrial genome is
      controlled by a set of nuclear-coded factors forming intricately interconnected
      circuits responsible for replication, recombination, repair and transmission to
      buds. Expression of the yeast mitochondrial genome is regulated mostly at the
      post-transcriptional level, and involves many general and gene-specific factors
      regulating splicing, RNA processing and stability and translation. A very
      interesting aspect of the yeast mitochondrial system is the relationship between
      genome maintenance and gene expression. Deletions of genes involved in many
      different aspects of mitochondrial gene expression, notably translation, result
      in an irreversible loss of functional mtDNA. The mitochondrial genetic system
      viewed from the systems biology perspective is therefore very fragile and lacks
      robustness compared to the remaining systems of the cell. This lack of robustness
      could be a legacy of the reductive evolution of the mitochondrial genome, but
      explanations involving selective advantages of increased evolvability have also
      been postulated.

PMID- 20056106
TI  - Detection of lipid domains in model and cell membranes by fluorescence lifetime
      imaging microscopy.
AB  - The discovery that the lipids constituting the plasma membrane are not randomly
      distributed, but instead are able to form laterally segregated lipid domains with
      different properties has given hints how the formation of such lipid domains
      influences and regulates many processes occurring at the plasma membrane. While
      in model systems these lipid domains can be easily accessed and their properties
      studied, it is still challenging to determine the properties of cholesterol rich
      lipid domains, the so called "Rafts", in the plasma membrane of living cells due
      to their small size and transient nature. One promising technique to address such
      issues is fluorescence lifetime imaging (FLIM) microscopy, as spatially resolved
      images make the visualization of the lateral lipid distribution possible, while
      at the same time the fluorescence lifetime of a membrane probe yields information
      about the bilayer structure and organization of the lipids in lipid domains and
      various properties like preferential protein-protein interactions or the
      enrichment of membrane probes. This review aims to give an overview of the
      techniques underlying FLIM probes which can be applied to investigate the
      formation of lipid domains and their respective properties in model membrane and
      biological systems. Also a short technical introduction into the techniques of a
      FLIM microscope is given.

PMID- 20056107
TI  - Functional impact of serial deletions at the C-terminus of the human GABArho1
      receptor.
AB  - GABArho1 receptors are formed by homopentameric assemblies that gate a chloride
      ion-channel upon activation by the neurotransmitter. Very little is known about
      the structural and functional roles played by the different domains that form
      each subunit; but one of them, the fourth transmembrane segment (TM4), is known
      to form a hydrophobic bundle together with three other TM segments that are
      necessary to stabilize the structure of the receptor. In this study we
      progressively removed amino acid residues from the C-terminus of the human
      GABArho1 and studied the functional properties of the receptor mutants expressed
      in X. laevis oocytes. We found that deletions of up to the last four residues
      gave rise to receptors that were still functional, generating currents of 3.92
      microA for the wt, 5.75 microA for S479X, 1.82 microA for F478X, 0.52 microA for
      I477X and 0.27 microA for S476X when exposed to 5 microM GABA; surprisingly, the
      mutant with one residue removed resulted more sensitive to the agonists. Further
      deletions, up to residue W475, resulted in receptors that did not gate an ion
      channel. In addition, deleting the signal sequence, from R2-A15, in the N
      terminus produced non-functional receptors. This study reveals that GABArho1 can
      tolerate removal of several residues that form the fourth transmembrane segment
      up to a critical point, signaled by W475, beyond which the mutant protein is
      translated but does not form functional receptors. A comparative study is
      presented of some electrophysiological and pharmacological properties of the
      deletion mutants that were able to generate GABA currents.

PMID- 20056108
TI  - Regenerating gene I regulates interleukin-6 production in squamous esophageal
      cancer cells.
AB  - Regenerating gene (REG) I plays important roles in cancer cell biology. The
      purpose of this study was to determine whether REG I affects cytokine production
      in cancer cells. We transfected TE-5 and TE-9 squamous esophageal cancer cells
      with REG Ialpha and Ibeta and examined its effects on cytokine expression. We
      found that transfecting TE-5 and TE-9 cells with REG I Ialpha and Ibeta led to
      significantly increased expression of interleukin (IL)-6 mRNA and protein, but it
      had little or no effect on expression of IL-2, IL-4, IL-5, IL-10, IL-12, IL-13,
      IL-17A, interferon-gamma, tumor necrosis factor-alpha, granulocyte-colony
      stimulating factor or transforming growth factor-beta1. The elevated IL-6
      expression seen in REG Ialpha transfectants was silenced by small interfering RNA
      mediated knockdown. These finding suggest that REG I may act through IL-6 to
      exert effects on squamous esophageal cancer cell biology.

PMID- 20056109
TI  - n-3, but not n-6 lipid particle uptake requires cell surface anchoring.
AB  - Omega-3 (n-3) fatty acids are emerging as bioactive agents protective against
      cardiovascular disease. However, their cellular delivery pathways are poorly
      defined. Here we questioned whether the uptake of n-3 triglyceride-rich particles
      (TGRP) is mediated by cell surface proteoglycans (PG) using LDL receptor
      (LDLR)+/+ and LDLR-/- cell models. LDLR+/+ but not LDLR-/- cells showed higher n
      6 over n-3 TGRP uptake. Removal of cell surface proteins and receptors by pronase
      markedly enhanced the uptake of n-3 but not n-6 TGRP. Lactoferrin blockage of
      apoE-mediated pathways decreased the uptake of n-6 TGRP by up to 85% (p<0.05) but
      had insignificant effect on n-3 TGRP uptake. PG removal by sodium chlorate in
      LDLR+/+ cells substantially reduced n-3 TGRP uptake but had little effect on n-6
      TGRP uptake. Thus, while n-6 TGRP uptake is preferentially mediated by LDLR
      dependent pathways, the uptake of n-3 TGRP depends more on PG and non-LDLR cell
      surface anchoring.

PMID- 20056110
TI  - The mitogaligin protein is addressed to the nucleus via a non-classical
      localization signal.
AB  - Mitogaligin, a protein encoded by galig, an internal cytotoxic gene of the
      galectin-3 locus, is mostly a mitochondrial protein. Mitochondrial targeting is
      due to an already identified mitochondrial localization signal. Interaction of
      mitogaligin with mitochondria leads to cytochrome c cytosolic leakage and
      ultimately to cell death. We have previously pointed out that mitogaligin can
      also be directed to the nucleus when the mitochondrial addressing signal is
      inactivated, indicating a possible dual intracellular localization of the
      protein. When expressed in the nucleus, mitogaligin exhibits also apoptotic
      properties leading to cell death. In this report, we show that nuclear addressing
      of mitogaligin depends on a sequence differing from classical signals containing
      basic, lysine or proline-tyrosine rich residues. The signal consists of a long
      sequence of amino acids residues based on a series of a short repetitive
      degenerated sequence.

PMID- 20056111
TI  - The role of DNA repair in benzene-induced carcinogenesis.
AB  - Benzene is a well-known human carcinogen, but the ultimate mode of action is
      still not known. Several reactive metabolites have been identified, including
      benzene oxide, phenol, hydrochinone, catechol and benzoquinones, generating
      different types of DNA lesions. Furthermore, the latter three metabolites may
      lead to the formation of reactive oxygen species (ROS) due to redox cycling,
      which give rise to oxidative DNA lesions and altered signaling pathways. Also,
      the inhibition of DNA topoisomerase II may result in DNA double strand breaks.
      Even though the exact contribution of the respective metabolites to benzene
      induced carcinogenicity is not yet resolved, the major DNA repair pathways such
      as base excision repair (BER), nucleotide excision repair (NER) and double strand
      break (DSB) repair are involved in the removal of benzene-induced DNA lesions.
      The observed target organ specificity may result from increased adduct formation,
      but also from poor repair in bone marrow progenitor cells. While especially
      excision repair pathways are predominantly error-free and thus protective, DSB
      repair is largely error prone and may contribute to benzene-induced genomic
      instability.

PMID- 20056113
TI  - Inhibitory effects of taurine and oat fiber on intestinal endotoxin release in
      rats.
AB  - Numerous studies have demonstrated that endotoxin plays an important role in the
      development and progression of hepatic cirrhosis. However, there is no effective
      remedy for the prevention and treatment of intestinal endotoxemia. Taurine has
      been reported to have beneficial effects on endotoxemia. Oats have been shown to
      absorb intestinal toxins and increase excretion of intestinal toxins. The present
      study was to investigate whether a combination of taurine and oat has an additive
      inhibitory effect on endotoxin release in a rat liver ischemia/reperfusion model.
      Our results showed that the combination of taurine (300mgkg(-1)d(-1)) and oat
      fiber (15gkg(-1)d(-1)) significantly reduced endotoxin levels in the portal vein
      by 36.3% when compared to the control group (0.168+/-0.035Eu/ml in the treatment
      group vs 0.264+/-0.058Eu/ml in the control group, P<0.01). The treatment of
      taurine (300mgkg(-1)d(-1)) and oat fiber (15gkg(-1)d(-1)) induced 21.5% and 18.4%
      reduction in endotoxin levels, respectively, when compared to the control group
      (P<0.05). We conclude that the combination of taurine and oat fiber achieved an
      additive inhibitory effect on intestinal endotoxin release, which might be an
      effective approach for the treatment of intestinal endotoxemia.

PMID- 20056112
TI  - Benzene exposure: an overview of monitoring methods and their findings.
AB  - Benzene has been measured throughout the environment and is commonly emitted in
      several industrial and transportation settings leading to widespread
      environmental and occupational exposures. Inhalation is the most common exposure
      route but benzene rapidly penetrates the skin and can contaminant water and food
      resulting in dermal and ingestion exposures. While less toxic solvents have been
      substituted for benzene, it still is a component of petroleum products, including
      gasoline, and is a trace impurity in industrial products resulting in continued
      sub to low ppm occupational exposures, though higher exposures exist in small,
      uncontrolled workshops in developing countries. Emissions from
      gasoline/petrochemical industry are its main sources to the ambient air, but a
      person's total inhalation exposure can be elevated from emissions from
      cigarettes, consumer products and gasoline powered engines/tools stored in
      garages attached to homes. Air samples are collected in canisters or on adsorbent
      with subsequent quantification by gas chromatography. Ambient air concentrations
      vary from sub-ppb range, low ppb, and tens of ppb in rural/suburban, urban, and
      source impacted areas, respectively. Short-term environmental exposures of ppm
      occur during vehicle fueling. Indoor air concentrations of tens of ppb occur in
      microenvironments containing indoor sources. Occupational and environmental
      exposures have declined where regulations limit benzene in gasoline (<1%) and
      cigarette smoking has been banned from public and work places. Similar controls
      should be implemented worldwide to reduce benzene exposure. Biomarkers of benzene
      used to estimate exposure and risk include: benzene in breath, blood and urine;
      its urinary metabolites: phenol, t,t-muconic acid (t,tMA) and S-phenylmercapturic
      acid (sPMA); and blood protein adducts. The biomarker studies suggest benzene
      environmental exposures are in the sub to low ppb range though non-benzene
      sources for urinary metabolites, differences in metabolic rates compared to
      occupational or animal doses, and the presence of polymorphisms need to be
      considered when evaluating risks from environmental exposures to individuals or
      potentially susceptible populations.

PMID- 20056114
TI  - Enhanced NMDAR1, NMDA2B and mGlu5 receptors gene expression in the cerebellum of
      insulin induced hypoglycaemic and streptozotocin induced diabetic rats.
AB  - Glucose homeostasis in humans is an important factor for the functioning of the
      nervous system. A decrease in glucose content below a minimal level or
      hypoglycemia is dangerous for cells of the central and peripheral nerve system.
      In the present study we showed the effects of insulin induced hypoglycaemia and
      streptozotocin induced diabetes on the cerebellar glutamate receptor subunits and
      glutamate transporter. Cerebellar dysfunction is associated with seizure
      generation, motor deficits and memory impairment. We found an up regulation in
      NMDA receptor number and gene expression of N-methyl-d-aspartic acid (NMDA(R1)),
      NMDA(2B), metabotrophic glutamate 5 (mGlu(5)) glutamate receptor subunits in
      experimental rats. The glutamate content was shown to be increased with decreased
      glutamate aspartate transporter (GLAST) gene expressions indicating lower
      reuptake of glutamate. The enhanced gene expression of NMDA(R1), NMDA(2B),
      mGlu(5) glutamate receptors were confirmed by immunohistochemistry studies. At
      the second messenger level, the IP3 content and IP3 receptors were enhanced in
      the cerebellum of both hypoglycaemic and diabetic rats increased. The present
      study showed that the enhanced glutamate content activates NMDA receptors,
      increasing the inositol triphosphate (IP3) content which mediates Ca(2+) overload
      in cells causing cell damage and neurodegeneration. Our results also showed that
      the enhanced glutamate receptor activity were more prominent in hypoglycaemic
      group compared to diabetic group. Further the neurodegeneration by the up
      regulation of glutamate receptor activity causing motor dysfunction was
      demonstrated by the Rotarod test. Thus our results suggest that enhanced NMDA
      receptor mediated neurodegeneration affect the motor learning and memory ability
      of an individual.

PMID- 20056115
TI  - Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of
      prostate cancer cells via inhibition of NF-kappaB.
AB  - Ginsenoside Rg3 has been a subject of interest for use as a cancer preventive or
      therapeutic agent. Nuclear factor-kappa (NF-kappaB) is constitutively activated
      in prostate cancer, and gives cancer cells resistance to chemotherapeutic agents.
      To investigate whether Rg3 can suppress the activation of NF-kappaB, and thus
      increase susceptibility of prostate (LNCaP and PC-3, DU145) cells against
      chemotherapeutics, prostate cancer cell growth as well as activation of NF-kappaB
      was examined. We found that a combination treatment of Rg3 (50 microM) with a
      conventional agent docetaxel (5 nM) was more effective in the inhibition of
      prostate cancer cell growth and induction of apoptosis as well as G(0)/G(1)
      arrest accompanied with the significant inhibition of NF-kappaB activity than
      those by treatment of Rg3 or docetaxel alone. It was also found that NF-kappaB
      target gene expression of Bax, caspase-3, and caspase-9 was much more
      significantly enhanced, but the expression of Bcl-2, inhibitor of apoptosis
      protein (IAP-1) and X chromosome IAP (XIAP), and the expression of cell cycle
      regulatory proteins cyclin B, D1 and E, and cyclin dependent kinases 2 and 4 was
      also much more significantly inhibited by the combination treatment. The
      combination of Rg3 (50 microM) with cisplatin (10 microM) and doxorubicin (2
      microM) was also more effective in the inhibition of prostate cancer cell growth
      and NF-kappaB activity than those by the treatment of Rg3 or chemotherapeutics
      alone. These results indicate that ginsenoside Rg3 inhibits NF-kappaB, and
      enhances the susceptibility of prostate cancer cells to docetaxel and other
      chemotherapeutics. Thus, ginsenoside Rg3 could be useful as an anti-cancer agent.

PMID- 20056116
TI  - Effect of chrysin on hepatoprotective and antioxidant status in D-galactosamine
      induced hepatitis in rats.
AB  - Chrysin is a natural, biologically active compound present in many plants and
      possesses potent anti-inflammatory, anticancer and antioxidation properties. This
      work was designed to investigate the effect of chrysin, on the hepatoprotective
      efficacy in d-galactosamine-intoxication rats. d-galactosamine-induced toxicity
      was manifested by the elevation of serum hepatic marker enzyme activities
      (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and
      gamma-glutamyl transpeptidase) and the lipid peroxidation process and by
      decreasing the antioxidant capacity of the plasma, erythrocyte and tissues.
      Treatment with chrysin (25, 50 and 100mg/kg body weight) decreased hepatic marker
      enzyme activities and lipid peroxidation products such as thiobarbituric acid
      reactive substances, lipid hydroperoxides and conjugated dienes, increased the
      activities of free-radical scavenging enzymes superoxide dismutase, catalase and
      glutathione peroxidase and the levels of non-enzymatic antioxidants reduced
      glutathione, vitamin C and vitamin E. These findings demonstrate that chrysin
      acts as a hepatoprotective and antioxidant agent against d-galactosamine-induced
      hepatotoxicity.

PMID- 20056117
TI  - Amoebae and algae can prolong the survival of Campylobacter species in co
      culture.
AB  - Several species of free-living amoebae can cause disease in humans. However, in
      addition to the direct pathogenicity of e.g. Acanthamoebae and Naegleria species,
      they are recognized as environmental hosts, indirectly involved in the
      epidemiology of many pathogenic bacteria. Although several studies have
      demonstrated intracellular survival of many different bacteria in these species,
      the extent of such interactions as well as the implications for the epidemiology
      of the bacterial species involved, are largely unknown and probably
      underestimated. In this study, we evaluated eight different unicellular
      eukaryotic organisms, for their potential to serve as environmental hosts for
      Campylobacter species. These organisms include four amoebozoas (Acanthamoeba
      polyphaga, Acanthamoeba castellanii, Acanthamoeba rhysodes and Hartmanella
      vermiformis), one alveolate (Tetrahymena pyriformis), one stramenopile (Dinobryon
      sertularia), one eugoenozoa (Euglena gracilis) and one heterolobosea (Naegleria
      americana). Campylobacter spp. including Campylobacter jejuni, Campylobacter coli
      and Campylobacter lari are the most common cause of gastroenteritis in the
      western world. Survival and replication of these three species as well as
      Campylobacter hyointestinalis were assessed in co-cultures with the eukaryotic
      organisms. Campylobacter spp. generally survived longer in co-cultures, compared
      to when incubated in the corresponding growth media. The eukaryotic species that
      best promoted bacterial survival was the golden algae D. sertularia. Three
      species of amoebozoas, of the genus Acanthamoeba promoted both prolonged survival
      and replication of Campylobacter spp. The high abundance in lakes, ponds and
      water distribution networks of these organisms indicate that they might have a
      role in the epidemiology of campylobacteriosis, possibly contributing to survival
      and dissemination of these intestinal pathogens to humans and other animals. The
      results suggest that not only C. jejuni, but a variety of Campylobacter spp. can
      interact with different eukaryotic unicellular organisms.

PMID- 20056118
TI  - Different regions of the class P-III snake venom metalloproteinase jararhagin are
      involved in binding to alpha2beta1 integrin and collagen.
AB  - SVMPs are multi-domain proteolytic enzymes in which disintegrin-like and cysteine
      rich domains bind to cell receptors, plasma or ECM proteins. We have recently
      reported that jararhagin, a P-III class SVMP, binds to collagen with high
      affinity through an epitope located within the Da-disintegrin sub-domain. In this
      study, we evaluated the binding of jararhagin to alpha(2)beta(1) integrin
      (collagen receptor) using monoclonal antibodies and recombinant jararhagin
      fragments. In solid phase assays, binding of jararhagin to alpha(2)beta(1)
      integrin was detectable from concentrations of 20 nM. Using recombinant fragments
      of jararhagin, only fragment JC76 (residues 344-421), showed a significant
      binding to recombinant alpha(2)beta(1) integrin. The anti-jararhagin monoclonal
      antibody MAJar 3 efficiently neutralised binding of jararhagin to collagen, but
      not to recombinant alpha(2)beta(1) integrin nor to cell-surface-exposed
      alpha(2)beta(1) integrin (alpha(2)-K562 transfected cells and platelets). The
      same antibody neutralised collagen-induced platelet aggregation. Our data suggest
      that jararhagin binding to collagen and alpha(2)beta(1) integrin occurs by two
      independent motifs, which are located on disintegrin-like and cysteine-rich
      domains, respectively. Moreover, toxin binding to collagen appears to be
      sufficient to inhibit collagen-induced platelet aggregation.

PMID- 20056119
TI  - Acute and subchronic administration of anandamide or oleamide increases REM sleep
      in rats.
AB  - Anandamide and oleamide, induce sleep when administered acutely, via the CB1
      receptor. Their subchronic administration must be tested to demonstrate the
      absence of tolerance to this effect, and that the sudden withdrawal of these
      endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle
      of rats was evaluated for 24h, under the effect of an acute or subchronic
      administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor
      antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that
      both acute and subchronic administration of eCBs increase REMS. During eCBs
      withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was
      efficacious to prevent REMS increase caused by both acute and subchronic
      administration of these eCBs, suggesting that this effect is mediated by the CB1
      receptor. Our data further support a role of the eCBs in REMS regulation.

PMID- 20056120
TI  - Phylogeny, genomic organization and expression of lambda and kappa immunoglobulin
      light chain genes in a reptile, Anolis carolinensis.
AB  - The reptiles are the last major taxon of jawed vertebrates in which
      immunoglobulin light chain isotypes have not been well characterized. Using the
      recently released genome sequencing data, we show in this study that the reptile
      Anolis carolinensis expresses both lambda and kappa light chain genes. The
      genomic organization of both gene loci is structurally similar to their
      respective counterparts in mammals. The identified lambda locus contains three
      constant region genes each preceded by a joining gene segment, and a total of 37
      variable gene segments. In contrast, the kappa locus contains only a single
      constant region gene, and two joining gene segments with a single family of 14
      variable gene segments located upstream. Analysis of junctions of the recombined
      VJ transcripts reveals a paucity of N and P nucleotides in both expressed lambda
      and kappa sequences. These results help us to understand the generation of the
      immunoglobulin repertoire in reptiles and immunoglobulin evolution in
      vertebrates.

PMID- 20056121
TI  - Phenotypic and molecular characterization of invasive serogroup W135 Neisseria
      meningitidis strains from 1990 to 2005 in Brazil.
AB  - OBJECTIVE: Neisseria meningitidis serogroup W135 has been associated with global
      outbreaks since the 2000 Hajj. Considering that N. meningitidis serogroup W135 is
      the third most prevalent serogroup isolated in Brazil in the last 10 years, and
      the possibility that the Hajj-related N. meningitidis serogroup W135 clone has
      been causing disease in Brazil, the present study characterized invasive N.
      meningitidis serogroup W135 isolates recovered in Brazil from 1990 to 2005.
      METHODS: The isolates were characterized by serotyping, PorA and PorB VR typing,
      FetA and 16S rRNA typing, multilocus sequence typing (MLST) and pulsed field gel
      electrophoresis (PFGE). RESULTS: Based on MLST, 73% of the isolates were
      clustered in one major clone of ST-11 complex/ET37 complex. Strains of this clone
      had the same STs, serotypes and PorA VR types as found in Hajj-related N.
      meningitidis serogroup W135 clone. One of these strains had the Hajj-2000
      outbreak strain genotype, including 16S rRNA gene sequence 31 and 84% relatedness
      by PFGE. CONCLUSION: Taken together, these data suggest that the Hajj-related N.
      meningitidis serogroup W135 clone is present in Brazil but has not yet caused a
      substantial number of infections. Given the emergence of N. meningitidis
      serogroup W135 globally and the unpredictability of meningococcal disease
      epidemiology, continued surveillance for this invasive N. meningitidis serogroup
      W135 clone is needed for control and prevention strategies.

PMID- 20056122
TI  - CD44 and hyaluronan promote invasive growth of B35 neuroblastoma cells into the
      brain.
AB  - Hyaluronan and its receptor CD44 are known to contribute to the invasive growth
      of different tumors of the central nervous system. It is not known, however, if
      CD44 is sufficient to activate invasive growth into the brain tissue. This study
      examines how CD44 regulates the motility and invasive growth of B35 neuroblastoma
      cells into a hyaluronan-rich environment. A comprehensive experimental approach
      was used encompassing biochemical techniques, single molecule microscopy,
      correlative confocal and scanning electron microscopy, morphometry of cellular
      extensions, live-cell imaging and tracking, transplantation onto organotypic
      brain slices, two-photon imaging and invasion assays. We found that CD44-GFP
      fusion protein was localized in filopodia and in focal bleb-like protrusions
      where it provided binding sites for hyaluronan. Transient expression of CD44-GFP
      was sufficient to increase the length of filopodia, to enhance cell migration and
      to promote invasive growth into hyaluronan-rich brain tissue. Thus, CD44 controls
      molecular devices localized in filopodia and bleb-like specializations of the
      cell surface that enhance cell migration and invasive growth.

PMID- 20056123
TI  - Cyclic RGD conjugated poly(ethylene glycol)-co-poly(lactic acid) micelle enhances
      paclitaxel anti-glioblastoma effect.
AB  - The use of glioblastoma-targeted drug delivery system facilitates efficient
      delivery of chemotherapeutic agents to malignant gliomas in the central nervous
      system while minimizing high systemic doses associated with debilitating
      toxicities. To employ the high binding affinity of a cyclic RGD peptide
      (c(RGDyK), cyclic Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine) with integrin
      alpha(v)beta(3) over-expressed on tumor neovasculature and U87MG glioblastoma
      cells, we prepared paclitaxel-loaded c(RGDyK)-Poly(ethylene glycol)-block
      poly(lactic acid) micelle (c(RGDyK)-PEG-PLA-PTX). In vitro physicochemical
      characterization of these novel micelles showed satisfactory encapsulated
      efficiency, loading capacity and size distribution. In vitro cytotoxicity studies
      proved that the presence of c(RGDyK) enhanced the anti-glioblastoma cell
      cytotoxic efficacy by 2.5 folds. The binding affinity of c(RGDyK)-PEG-PLA micelle
      with U87MG cells was also investigated. The competitive binding IC(50) value of
      c(RGDyK)-PEG-PLA micelle was 26.30 nM, even lower than that of c(RGDyK) (56.23
      nM). In U87MG glioblastoma-bearing nude mice model, biodistribution of (125)I
      radiolabeled c(RGDyK)-PEG-PLA or DiR encapsulated micelles and anti-glioblastoma
      pharmacological effect was investigated after intravenous administration.
      c(RGDyK)-PEG-PLA micelle accumulated in the subcutaneous and intracranial tumor
      tissue, and when loaded with PTX (c(RGDyK)-PEG-PLA-PTX), exhibited the strongest
      tumor growth inhibition among the studied paclitaxel formulations. The anti
      glioblastoma effect of c(RGDyK)-PEG-PLA-PTX micelle was also reflected in the
      median survival time of mice bearing intracranial U87MG tumor xenografts where
      the median survival time of c(RGDyK)-PEG-PLA-PTX micelle-treated mice (48 days)
      was significantly longer than that of mice treated with PEG-PLA-PTX micelle (41.5
      days), Taxol (38.5 days) or saline (34 days). Therefore, our results suggested
      that c(RGDyK)-PEG-PLA micelle may be a potential drug delivery system in the
      treatment of integrin alpha(v)beta(3) over-expressed glioblastoma.

PMID- 20056124
TI  - Effect of temporally controlled release of dexamethasone on in vivo chondrogenic
      differentiation of mesenchymal stromal cells.
AB  - Controlled release of biologically active molecules is of importance in
      regulating stem cell migration and differentiation. The purpose of this study is
      to investigate the effect of dexamethasone (Dex) released from two different sets
      of poly(lactic-co-glycolic acid) (PLGA) microspheres on chondrogenic
      differentiation of mesenchymal stromal cells (MSCs) in vivo. Either nonporous
      (NPMS) or porous (PMS) Dex-loaded PLGA microspheres were fabricated using double
      emulsion-solvent evaporation method. Each set of microspheres was combined with a
      composite hydrogel of hyaluronic acid (HA) and Pluronic F127 along with the
      addition of rabbit MSCs. These hydrogel constructs were then injected
      subcutaneously in nude mouse and they were retrieved after 2 and 4 weeks
      respectively. Each group of microspheres presented significantly different in
      vitro release profiles of Dex on a temporal basis. The composite hydrogel carried
      a property of sol-gel transition and thus formed a gel at body temperature. It
      was interesting that the in vitro cell viability in the hydrogel containing NPMS
      was found better than the one with PMS. A sign of chondrogenic differentiation
      from the transplanted samples was identified from semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR). The gene expression of the
      cartilage-specific markers Sox 9 and type II collagen was notably upregulated in
      the PMS-loaded construct than in the NPMS-loaded one. Alcian blue staining
      displayed that the amount of cartilage-specific extracellular matrix
      glycosaminoglycan (GAG) was more visibly pronounced in the PMS group.
      Immunohistochemical analysis of the retrieved constructs also supported that
      synthesis of type II collagen was more active with the PMS group. The present
      work suggested that an in vivo chondrogenic potential of MSCs could be affected
      by characteristic release profile of chondrogenic factor in vitro.

PMID- 20056125
TI  - Therapeutic dose as the point of departure in assessing potential health hazards
      from drugs in drinking water and recycled municipal wastewater.
AB  - The detection of drugs in drinking water sources has raised questions related to
      safety. In the absence of regulatory or other official guidance, water utilities
      are faced with a problem of which drugs should be monitored and the detection
      limits that should be required. The US FDA summarizes data required for drug
      approval and post marketing adverse reaction reporting. The use of these data as
      a means of arriving at concentrations in water where adverse health effects are
      minimal or non-existent was explored. The minimum therapeutic dose was assumed an
      appropriate point of departure. Appropriate uncertainty factors could be applied
      depending upon the qualitative and quantitative nature of the data that are
      available. Assumptions inherent in US FDA's approval of drugs for use in subsets
      of the population relative to the broader concerns that arise for exposures of
      the entire population had to be considered. Additional questions are; whether the
      drug under consideration is carcinogenic, carries pregnancy and lactation
      warnings, approval for limited vs. chronic use, exposures to multiple compounds
      that could act in additive or synergistic ways, and the seriousness of toxicities
      that are observed. Aside from these considerations, a combined uncertainty factor
      of 1000 appeared adequate.

PMID- 20056126
TI  - B-lymphoma cells escape rituximab-triggered elimination by NK cells through
      increased HLA class I expression.
AB  - OBJECTIVE: Antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK)
      cells is a major effector mechanism of the monoclonal anti-CD20 antibody
      rituximab in eliminating B-cell lymphomas. Resistance to this treatment occurs,
      although CD20 antigen is expressed on the tumor cells. MATERIALS AND METHODS: A
      model of ADCC was established by stimulating human bulk NK cells and inhibitory
      killer immunoglobulin receptor (KIR)-defined NK cells from human leukocyte
      antigen (HLA)-typed donors. NK-cell activation was triggered via stimulation of
      the Fc receptor with immunoglobulin G aggregates, rituximab-labeled HLA-defined
      CD20-positive B-lymphoblast cell lines or CD20-positive B-lymphoma cell lines.
      The effect of KIR ligation by anti-KIR antibodies and HLA, the HLA expression
      density and rituximab concentrations on the efficacy of ADCC were analyzed in
      granzyme B ELISPOT measuring NK-cell activation and fluorescein-activated cell
      sorting cytotoxicity assay. RESULTS: HLA, but not CD20 expression density
      correlated with NK-cell activity against rituximab-labeled targets. ADCC was
      increased or decreased following HLA shielding or KIR activation by anti-KIR
      antibodies, respectively. Herein we show that rituximab-induced ADCC is
      attenuated upon ligation of KIR by HLA molecules expressed on human B-lymphoma
      target cells. Moreover, anti-KIR antibodies do not only block KIR/HLA
      interactions, but display agonistic effects at the KIR, which has to be
      considered for therapeutical applications. CONCLUSION: KIR activation and HLA
      expression density are critical determinants for the efficacy of rituximab
      treatment. An explanation for the failure of rituximab treatment may be the
      protection of the tumor cells from ADCC by inhibiting NK-cell function with their
      surface HLA.

PMID- 20056127
TI  - Genistein up-regulates the iron efflux system in glial cells.
AB  - Astrocytes accumulate iron under chronic oxidative stress conditions in ageing
      and neurological disorders. The soybean isoflavone genistein possesses
      antioxidant properties and selective estrogen-like activities. Here, a possible
      role of genistein in modulation of iron transport was explored in glial cells.
      Genistein significantly increased iron export through estrogen receptor-beta
      dependent p38 MAPK activation. Evidence is presented that this effect is
      associated to a p38 MAPK-triggered up-regulation of the iron export system made
      by ceruloplasmin and ferroportin-1, a pathway requiring activation of the
      transcription factor C/EBP.

PMID- 20056128
TI  - Accumulation of tumor-suppressor PTEN in Alzheimer neurofibrillary tangles.
AB  - The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively
      regulates intracellular levels of PIP3 and antagonizes the PI3K signaling pathway
      important for cell survival. The present study determined whether altered
      distribution of PTEN occurs in Alzheimer's disease (AD) brains. We investigated a
      possible role for PTEN in postmortem brain tissues from elderly controls and
      patients with AD using immunoblotting and microscopic analyses. Intense
      immunolabeling was found in the large neurons such as pyramidal cells. In normal
      neurons, PTEN was located in the nucleus, the cytoplasm of cell bodies and the
      proximal portion of apical dendrites. Reduced expression and redistribution of
      PTEN was seen in the remaining neurons in AD. In addition, PTEN was redistributed
      in damaged neurons from the nucleus and cytoplasm to neuritic pathology such as
      intracellular neurofibrillary tangles (NFTs), neuropil threads and dystrophic
      neurites within senile plaques in AD hippocampus, subiculum, entorhinal cortex
      and angular gyrus. Furthermore, double immunofluorescence staining showed dual
      labeling of intracellular NFTs for PTEN and tau, labeling of some axons for PTEN
      and phosphorylated neurofilament, and weak labeling of a few reactive astrocytes
      around senile plaques for PTEN and GFAP. Double labeling of NFTs was observed in
      a subset of tangle-bearing neurons either for PTEN and GSK3beta or for PTEN and
      MEK. Thus our results suggest that PTEN delocalized from the nucleus to the
      cytoplasm and to intracellular NFTs may cause a deregulation of PI3K pathway in
      the cytoplasm and may induce the nuclear dysfunction of PTEN in AD degenerating
      neurons.

PMID- 20056129
TI  - Toll-like receptor 2 and facial motoneuron survival after facial nerve axotomy.
AB  - We have previously demonstrated that CD4(+) Th2 lymphocytes are required to
      rescue facial motoneuron (FMN) survival after facial nerve axotomy through
      interaction with peripheral antigen presenting cells, as well as CNS resident
      microglia. Furthermore, the innate immune molecule, toll-like receptor 2 (TLR2),
      has been implicated in the development of Th2-type immune responses and can be
      activated by intracellular components released by dead or dying cells. The role
      of TLR2 in the FMN response to axotomy was explored in this study, using a model
      of facial nerve axotomy at the stylomastoid foramen in the mouse, in which blood
      brain-barrier (BBB) permeability does not occur. After facial nerve axotomy, TLR2
      mRNA was significantly upregulated in the facial motor nucleus and co
      immunofluorescence localized TLR2 to CD68(+) microglia, but not GFAP(+)
      astrocytes. Using TLR2-deficient (TLR2(-/-)) mice, it was determined that TLR2
      does not affect FMN survival levels after axotomy. These data contribute to
      understanding the role of innate immunity after FMN death and may be relevant to
      motoneuron diseases, such as amyotrophic lateral sclerosis (ALS).

PMID- 20056130
TI  - Cyclophosphamide promotes cell survival via activation of intracellular signaling
      in cultured cortical neurons.
AB  - Cyclophosphamide (CP) has been used as an antitumour agent or immunosuppressant
      clinically, though the potential biological role of CP in the central nervous
      system (CNS) has not been clarified. In the present study, we found that
      pretreatment with CP prevented neuronal cell death caused by serum deprivation in
      cultured cortical neurons. Interestingly, CP stimulated activation of PI3K
      (phosphatidylinositol 3 kinase) and MAPK/ERK (mitogen-activated protein
      kinase/extracellular signal-regulated kinase) pathways, which are known as
      survival-promoting intracellular signalings. Furthermore, CP increased the
      expression of Bcl2, an anti-apoptotic factor. In the presence of inhibitors for
      PI3K or MAPK/ERK pathways, the CP-dependent neuronal survival and Bcl-2 up
      regulation were both abolished. Importantly, significant increase in BDNF (brain
      derived neurotrophic factor) expression was induced by CP application, implying
      that BDNF up-regulation is involved in the CP effect. We propose that CP has a
      protective effect on CNS neurons via the activation of intracellular signalings,
      and up-regulation of Bcl2 and BDNF.

PMID- 20056131
TI  - Evidence for functional, inhibitory, histamine H3 receptors in rat carotid body
      Type I cells.
AB  - The Type I cells are the sensory elements of the carotid bodies and play a
      critical role in defining the ventilatory response to hypoxia and hypercapnia.
      Type I cells release multiple neurotransmitters during a chemosensory stimulus
      resulting in increased firing of the carotid sinus nerve and modification of the
      breathing pattern. While much is known about the actions of individual
      neurotransmitters in this system, very little is known about how multiple
      neurotransmitters may integrate to shape the output of the carotid body. Recent
      data has indicated that the neurotransmitter histamine does not excite isolated
      Type I cells despite being released during hypoxia and its receptors being
      present on the Type I cells. Here the hypothesis that histamine might modulate an
      excitatory neurotransmitter such as acetylcholine was tested. Using calcium
      imaging techniques it was found that histamine attenuated calcium signaling
      events initiated by the muscarinic acetylcholine receptor agonist acetyl-beta
      methylcholine via an H3 receptor mediated mechanism. In summary, these results
      suggest that when acetylcholine and histamine are co-released from Type I cells
      in response to chemostimuli, histamine may attenuate or modulate the excitatory
      presynaptic actions of acetylcholine.

PMID- 20056132
TI  - DNA damage after intracerebroventricular injection of ouabain in rats.
AB  - There is an emerging body of data suggesting that bipolar disorder is associated
      with DNA damage. Intracerebroventricular (i.c.v.) administration of ouabain in
      rats results in manic-like alterations. We evaluated DNA damage of peripheral
      blood, cerebrospinal fluid and hippocampus of rats after i.c.v. ouabain
      injection. Ouabain-induced hyperlocomotion was examined in an open field.
      Additionally, we used single cell gel electrophoresis (comet assay) to measure
      early transient damage in cerebrospinal fluid (CSF), hippocampus and blood; and
      the micronucleus test to measure persistent damage in total blood samples of rats
      after ouabain administration. Our findings demonstrated that ouabain induced
      hyperlocomotion in rats, and this response remained up to 7 days following a
      single i.c.v. injection. In addition, we observed that the persistent increase in
      the rat spontaneous locomotion is associated with increased hippocampal and
      peripheral index of early DNA damage in rats. No significant alterations were
      observed in the micronucleus frequency in total blood samples of the rats after
      the ouabain i.c.v. injection. These results suggest that ouabain may induce
      peripheral and central early DNA damage, but this early damage may be repaired.

PMID- 20056133
TI  - Anticonvulsive effects of the dopamine agonist lisuride maleate after
      experimental traumatic brain injury.
AB  - Traumatic brain injury is a heterogeneous disease, encompassing a wide range of
      pathologies. The dopamine agonist lisuride is well established in the therapy of
      Parkinson's disease. Additionally to its dopaminergic effects it decreases
      prolactine release, reducing the amount of inflammatory mediators such as TNF
      alpha or Il-6. Lisuride has strong binding affinity to serotonergic and
      histaminergic receptors on neuronal and glial cells leading to scavenging of
      highly reactive free radicals. Due to its interaction with dopaminergic D2 and D4
      receptors as well as 5-HT-1A receptors, NMDA-receptor signaling and glutamate
      mediated excitotoxicity can be modulated beneficially. Despite of these promising
      neuroprotective effects, experimental data scrutinizing the effects of lisuride
      after acute brain injury are sparse. We therefore investigated the effect of
      lisuride after controlled cortical impact injury (CCII) in rats. 70 male Sprague
      Dawley rats were randomized to lisuride or to placebo treatment by an initial
      s.c. loading dose (0.3mg/kg BW) and following continuous application (0.5mg/kg/d)
      by s.c. implanted osmotic pumps. In three experimental groups we determined
      (sub)acute neuro-physiological changes after trauma. Mean arterial blood
      pressure, intracranial pressure, and electrical brain activity were monitored
      acutely for up to 3h after trauma. Brain edema formation was assessed 24h after
      CCII. Furthermore, contusion volumes were quantified by magnetic resonance
      tomography and neurological testing was performed for up to 7 days after injury.
      Associated with the administration of lisuride there was a significant reduction
      in duration and number of post-traumatic seizures. Despite of a sustained
      arterial hypotension following the initial bolus administration in the treatment
      group, contusion volumes and neurological function tests did not differ
      significantly in comparison to the control group. Overall, lisuride seems to have
      significant anticonvulsive effects but seems not to influence secondary brain
      damage in this experimental model.

PMID- 20056134
TI  - Insulin alters the expression of components of the Wnt signaling pathway
      including TCF-4 in the intestinal cells.
AB  - BACKGROUND: Epidemiological and experimental evidence that support the
      correlation between Type 2 diabetes mellitus (T2D) and increased risks of
      colorectal cancer formation have led us to hypothesize the existence of molecular
      crosstalk between insulin and canonical Wnt signaling pathways. Insulin was shown
      to stimulate Wnt target gene expression, utilizing the effector of the Wnt
      signaling pathway. Whether insulin affects expression of components of Wnt
      pathway has not been extensively examined. METHODS: cDNA microarray was utilized
      to assess the effect of insulin on gene expression profile in the rat intestinal
      non-cancer IEC-6 cell line, followed by real-time RT-PCR, Western blotting and
      reporter gene analyses in intestinal cancer and non-cancer cells. RESULTS:
      Insulin was shown to alter the expression of a dozen of Wnt pathway related genes
      including TCF-4 (=TCF7L2) and frizzled- (Fzd-4). The stimulatory effect of
      insulin on TCF-4 expression was then confirmed by real-time RT-PCR, Western
      blotting and luciferase reporter analyses, while the activation on Fzd-4 was
      confirmed by real-time PCR. GENERAL SIGNIFICANCE: Our observations suggest that
      insulin may crosstalk with the Wnt signaling pathway in a multi-level fashion,
      involving insulin regulation of the expression of Wnt target genes, a Wnt
      receptor, as well as mediators of the Wnt signaling pathway.

PMID- 20056135
TI  - Neuronostatin is co-expressed with somatostatin and mobilizes calcium in cultured
      rat hypothalamic neurons.
AB  - Neuronostatin (NST) is a newly identified peptide of 13-amino acids encoded by
      the somatostatin (SST) gene. Using a rabbit polyclonal antiserum against the
      human NST, neuronostatin-immunoreactive (irNST) cells comparable in number and
      intensity to somatostatin immunoreactive (irSST) cells were detected in the
      hypothalamic periventricular nucleus. Fewer and/or less intensely labeled irNST
      cells were noted in other regions such as the hippocampus, cortex, amygdala, and
      cerebellum. Double-labeling hypothalamic sections with NST- and SST-antiserum
      revealed an extensive overlapping of irNST and irSST cells in the periventricular
      nucleus. Pre-absorption of the NST-antiserum with NST (1 microg/ml) but not with
      SST (1 microg/ml) abrogated irNST and vice versa. The activity of NST on
      dissociated and cultured hypothalamic neurons was assessed by the Ca(2+) imaging
      method. NST (10, 100, 1000 nM) concentration-dependently elevated intracellular
      Ca(2+) concentrations [Ca(2+)](i) in a population of hypothalamic neurons with
      two distinct profiles: (1) a fast and transitory increase in [Ca(2+)](i), and (2)
      an oscillatory response. Whereas, SST (100 nM) reduced the basal [Ca(2+)](i) in
      21 of 61 hypothalamic neurons examined; an increase was not observed in any of
      the cells. Optical imaging with a slow-responding voltage sensitive dye
      DiBAC(4)(3) showed that NST (100 nM) depolarized or hyperpolarized; whereas, SST
      (100 nM) hyperpolarized a population of hypothalamic neurons. The result shows
      that NST and SST, though derived from the same precursor protein, exert different
      calcium mobilizing effects on cultured rat hypothalamic neurons, resulting in
      diverse cellular activities.

PMID- 20056136
TI  - Nicotine increases the expression of neurotrophin receptor tyrosine kinase
      receptor A in basal forebrain cholinergic neurons.
AB  - In this study, we investigated whether the potential positive effects of nicotine
      in Alzheimer's disease (AD) may involve neurotrophic factors, such as nerve
      growth factor (NGF), closely associated with basal forebrain (BF) cholinergic
      function and survival. To this aim, we studied the effects of prolonged nicotine
      treatment on neurotrophin receptors expression and on NGF protein levels in the
      rat BF cholinergic circuitry. Both in vivo and in vitro experiments were
      conducted. We found that s.c. nicotine infusion (1.2 mg free base/kg/d delivered
      by mini-pumps for 7 days) induced in vivo an increase in tyrosine kinase receptor
      A (TrkA)-but not TrkB, TrkC or low affinity neurotrophin receptor p75 (p75)
      expression in BF cholinergic neurons targeting the cerebral cortex. Nicotine did
      not produce statistically significant long-lasting effects on NGF levels in the
      cerebral cortex, or in the BF. In vitro experiments performed on primary BF
      neuronal cultures, showed that 72 h exposure to nicotine increased both TrkA
      expression, and NGF release in culture medium. Neutralization experiments with an
      anti-NGF antibody showed that NGF presence was not necessary for nicotine-induced
      increase of TrkA levels in cultured cholinergic neurons, suggesting that nicotine
      may act through NGF-independent mechanisms. This study shows that nicotine,
      independently of its action on NGF levels, may contribute to the restoration of
      the trophic support to BF cholinergic neurons by increasing TrkA levels.

PMID- 20056137
TI  - Alpha-synuclein deficiency affects brain Foxp1 expression and ultrasonic
      vocalization.
AB  - Alpha-synuclein is an abundant protein implicated in synaptic function and
      plasticity, but the molecular mechanism of its action is not understood. Missense
      mutations and gene duplication/triplication events result in Parkinson's disease,
      a neurodegenerative disorder of old age with impaired movement and emotion
      control. Here, we systematically investigated the striatal as well as the
      cerebellar transcriptome profile of alpha-synuclein-deficient mice via a genome
      wide microarray survey in order to gain hypothesis-free molecular insights into
      the physiological function of alpha-synuclein. A genotype-dependent, specific and
      strong downregulation of forkhead box P1 (Foxp1) transcript levels was observed
      in all brain regions from postnatal age until old age and could be validated by
      qPCR. In view of the co-localization and heterodimer formation of FOXP1 with
      FOXP2, a transcription factor with a well established role for vocalization, and
      the reported regulation of both alpha-synuclein and FOXP2 expression during avian
      song learning, we performed a detailed assessment of mouse movements and
      vocalizations in the postnatal period. While there was no difference in isolation
      induced behavioral activity in these animals, the alpha-synuclein-deficient mice
      exhibited an increased production of isolation-induced ultrasonic vocalizations
      (USVs). This phenotype might also reflect the reduced expression of the anxiety
      related GABA-A receptor subunit gamma 2 (Gabrg2) we observed. Taken together, we
      identified an early behavioral consequence of alpha-synuclein deficiency and
      accompanying molecular changes, which supports the notion that the neural
      connectivity of sound or emotion control systems is affected.

PMID- 20056138
TI  - Improvement of postural adjustment steps in hemiparkinsonian rats chronically
      treated with caffeine is mediated by concurrent blockade of A1 and A2A adenosine
      receptors.
AB  - Chronic treatment with the non-selective adenosine receptor antagonist caffeine
      produces full recovery of the contralateral adjusting steps in hemiparkinsonian
      rats. In order to disclose which adenosine receptor subtype mediates this effect,
      a group of hemiparkinsonian rats (n=9) was treated with caffeine (5.15
      mumol/kg/day), or equimolar doses of selective A1 (DPCPX) or A2A (ZM 241385)
      adenosine receptor antagonists, administered in a counterbalanced order over
      periods of 3 weeks, interspersed with equivalent washout intervals. Treatment
      with ZM 241385 caused full recovery (102+/-6%) of the contralateral forepaw
      stepping, while the maximal effect of DPCPX was only 73+/-7% of that produced by
      caffeine. The maximal effect of caffeine and ZM 241385 remained stable throughout
      the treatment period. The response to DPCPX showed more fluctuations, but
      tolerance did not develop. Stepping improvement was significantly faster with
      DPCPX than with ZM 241385, while caffeine had intermediate values. Stepping
      decrease after treatment interruption was faster with ZM 241385 than with
      caffeine, while DPCPX had intermediate values. In other experiments with the same
      rats, addition of the A2AR agonist CGS 21680 (5.15 mumol/kg) or the A1R agonist
      CCPA (2.71 mumol/kg) during the second week of caffeine treatment reversed the
      improvement of contralateral stepping by 59+/-4% and 30+/-3%, respectively. The
      combined treatment with CGS 21680 and CCPA caused complete reversal of the
      contralateral stepping recovery afforded by caffeine, which was more than
      additive (114+/-5%) compared with the sum of the maximal inhibition produced by
      either agonist administered alone (89+/-4%). In all cases, after interrupting the
      adenosine agonists, the effect of caffeine was fully restored. None of the
      aforementioned treatments induced significant changes in the stepping of the
      ipsilateral forepaw. Collectively, these results suggest that the improvement of
      postural adjustments induced by chronic treatment with low doses of caffeine in
      hemiparkinsonian rats is mediated by concurrent blockade of A1 and A2A adenosine
      receptors, with a larger involvement of the latter.

PMID- 20056139
TI  - Projections from the inferior colliculus to the tectal longitudinal column in the
      rat.
AB  - We have used the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) to
      study with albino rats the projections from the inferior colliculus (IC) to the
      tectal longitudinal column (TLC), a newly discovered nucleus that spans the
      midbrain tectum longitudinally, on each side of the midbrain, immediately above
      the periaqueductal gray matter. We studied the projections of the medial IC,
      which includes the classical central nucleus (CNIC) and the dorsal cortex (DCIC),
      and those of the lateral IC, equivalent to the classical external cortex (ECIC).
      Following unilateral injections of PHA-L into the medial IC, numerous terminal
      fibers are labeled bilaterally in the TLC. The ipsilateral projection is denser
      and targets the entire nucleus, whereas the contralateral projection targets
      significantly only the caudal half or two-thirds of the TLC. Fibers from the
      medial IC reach the TLC by two routes: as collaterals of axons that travel in the
      commissure of the IC and as collaterals of thick ipsilateral colliculogeniculate
      axons; the latter travel through the deep superior colliculus on their way to the
      TLC. Within the TLC, individual IC fibers tend to run longitudinally. The
      injection of PHA-L into the lateral IC indicates that this subdivision sends a
      weak, bilateral projection to the TLC whose trajectory, morphology and
      distribution are similar to those of the projection from the medial IC. These
      results demonstrate that all subdivisions of the IC send projections to the TLC,
      suggesting that the IC may be one of the main sources of auditory input to this
      tectal nucleus.

PMID- 20056141
TI  - Herb medicine Gan-fu-kang attenuates liver injury in a rat fibrotic model.
AB  - AIM OF THE STUDY: To verify therapeutic effects of Gan-fu-kang (GFK), a
      traditional Chinese medicine compound, in a rat model and to investigate the
      underlying mechanisms. MATERIALS AND METHODS: Liver fibrosis was established by
      12 weeks of carbon tetrachloride (CCl(4)) treatment (0.5mg/kg, twice per week)
      followed by 8 weeks of "recovery" in rats. Rats randomly received GFK (31.25,
      312.5 and 3125 mg/kg/day, p.o.) or vehicle from weeks 9 to 20, and were
      sacrificed at the end of week 20 for histological, biochemical, and molecular
      biological examinations. In a separate set of experiments, rats received 12 weeks
      of CCl(4) treatment, concomitant with GFK (312.5mg/kg/day, p.o.) during the same
      period in some subjects, but were then sacrificed immediately. An additional
      group of rats receiving no CCl(4) treatment served as normal controls. RESULTS
      AND CONCLUSIONS: (1) CCl(4) treatment resulted in severe liver damage and
      fibrosis. (2) In the main block of the 20-week study, GFK attenuated liver damage
      and fibrosis. (3) In the 12-week study, GFK produced prevention effect against
      hepatic injury. (4) GFK suppressed the expression of tissue inhibitor of
      metalloproteinase-1 (TIMP-1), type I collagen, platelet-derived growth factor-BB
      (PDGF-BB)/PDGF receptor-beta chains (PDGFRbeta) and mitogen-activated protein
      kinases (MAPKs)/active protein-1 (AP-1) signal pathways. Taken together, these
      results indicated that GFK could attenuate liver injuries in both settings. Our
      findings also suggest that the AP-1 pathway is the likely molecular substrate for
      the observed GFK effects.

PMID- 20056140
TI  - Prestin and the cholinergic receptor of hair cells: positively-selected proteins
      in mammals.
AB  - The hair cells of the vertebrate inner ear posses active mechanical processes to
      amplify their inputs. The stereocilia bundle of various vertebrate animals can
      produce active movements. Though standard stereocilia-based mechanisms to promote
      amplification persist in mammals, an additional radically different mechanism
      evolved: the so-called somatic electromotility which refers to the
      elongation/contraction of the outer hair cells' (OHC) cylindrical cell body in
      response to membrane voltage changes. Somatic electromotility in OHCs, as the
      basis for cochlear amplification, is a mammalian novelty and it is largely
      dependent upon the properties of the unique motor protein prestin. We review
      recent literature which has demonstrated that although the gene encoding prestin
      is present in all vertebrate species, mammalian prestin has been under positive
      selective pressure to acquire motor properties, probably rendering it fit to
      serve somatic motility in outer hair cells. Moreover, we discuss data which
      indicates that a modified alpha10 nicotinic cholinergic receptor subunit has co
      evolved in mammals, most likely to give the auditory feedback system the
      capability to control somatic electromotility.

PMID- 20056142
TI  - Stereological assessment of extracellular polymeric substances, exo-enzymes, and
      specific bacterial strains in bioaggregates using fluorescence experiments.
AB  - This review addresses the introduction of fluorescent molecular tags into exo
      enzymes and extra polymeric substances of bioaggregates and the use of confocal
      laser scanning microscopy (CLSM) to map their role, purpose and quantitative
      description of the biological processes they undertake. Multiple color staining
      coupled with CLSM and fluorescent in situ hybridisation (FISH) and flow cytometry
      have identified the individual polymeric substances, whether they are proteins,
      lipids, polysaccharides, nucleic acids or antibodies, as well as the
      microorganisms in the bioaggregate. Procedures are presented for simultaneous
      multicolor staining with seven different fluorochromes - SYTOX Blue for nucleic
      acids; Nile red for lipids; Calcofluor white [CW] for beta-polysaccharides;
      concanavalin A [Con A] for alpha-poly-saccharides; fluorescein-isothiocyanate
      [FITC] for proteins; SYTO 63 for live microbial cells and Calcium Green for
      monitoring calcium levels in the microbial cells. For the distribution of certain
      microbial strains, metabolic enzymes and extrapolymeric substances to be
      quantitatively described the generated colored images are converted into digital
      forms under specific predefined criteria. Procedures and computer software
      programs (Amira; MATLAB) are presented in order to quantitatively establish grid
      patterns from the CLSM images. The image is digitized using a threshholding
      algorithm followed by a reconstruction of the image as a volumetric grid for
      finite element simulation. The original color image is first converted to a grey
      followed by resizing, detection and modification of bilevel images and finally a
      total reversal of the image colors. The grid file is then used by specific
      computer software (Gambit, Fluent) for further numerical studies incorporating
      chemical reactions, transport processes and computational fluid dynamics
      including intra-bioaggregate fluid flow, and heat and mass transfer within the
      bioaggregate matrix.

PMID- 20056143
TI  - Detection and differentiation of Clostridium botulinum type A strains using a
      focused DNA microarray.
AB  - A focused oligonucleotide microarray featuring 62 probes targeting strain
      variable regions of the Clostridium botulinum strain ATCC 3502 genome sequence
      was developed to differentiate C. botulinum type A strains. The strain variable
      regions were selected from deletions identified among a panel of 10 type A
      strains compared to the strain ATCC 3502 genome sequence using high density
      comparative genomic hybridization microarrays. The focused microarray also
      featured specific probes for the detection of the neurotoxin genes of various
      serotypes (A-G), toxin gene cluster components (ha70 and orfX1), and fldB as a
      marker for proteolytic clostridia (Group I). Eight pairs of strains selected from
      separate type A botulism outbreaks were included in the 27 subtype A1-A4 strains
      examined in this study. Each outbreak related strain pair consisted of strains
      isolated from different sources (stool and food). Of the eight outbreak related
      strain pairs, six groups of strains with indistinguishable hybridization patterns
      were identified. Outbreak related strains were shown to have identical
      hybridization patterns. Strain pairs from three separate outbreaks involving
      strains harboring both the type A neurotoxin gene (bont/A) and an unexpressed
      type B neurotoxin gene (bont/B) shared the same probe hybridization profile. The
      focused microarray format provides a rapid approach for neurotoxin gene detection
      and preliminary determination of the relatedness of strains isolated from
      different sources.

PMID- 20056144
TI  - Regulation of PC12 cell survival and differentiation by the new P2Y-like receptor
      GPR17.
AB  - The P2Y-like receptor GPR17 has been reported to respond to both uracil
      nucleotides and cysteinyl-leukotrienes (cysLTs), such as UDP-glucose and LTD(4).
      Our previous data suggest a potential role for GPR17 in regulation of both cell
      viability and differentiation state of central nervous system cells. On this
      basis, in the present paper we investigated the effect of GPR17 receptor ligands
      on PC12 cell viability, following induction of morphological differentiation by
      nerve growth factor (NGF). In addition, the role of GPR17 ligands, either alone
      or in combination with growth factors, on the degree of PC12 cell differentiation
      was investigated. GPR17, which was not basally expressed in undifferentiated PC12
      cells, was specifically induced by a 10day-treatment with NGF, suggesting a role
      in the control of neuronal specification. Both UDP-glucose and LTD(4), agonists
      at the nucleotide and cysLT GPR17 binding sites, respectively, induced a
      significant pro-survival effect on PC12 cells after priming with NGF. By in vitro
      silencing experiments with specific small interfering RNAs and by using receptor
      antagonists, we confirmed that the agonist effects are indeed mediated by the
      selective activation of GPR17. We also demonstrated that GPR17 agonists act, both
      alone and synergistically with NGF, to promote neurite outgrowth in PC12 cells.
      In addition, GPR17 ligands were able to confer an NGF-like activity to the
      epidermal growth factor (EGF), that, under these experimental conditions, also
      promoted cell differentiation and neurite elongation. Finally, we show that GPR17
      ligands activate the intracellular phosphorylation of both ERK 1/2 and p38
      kinases, that have been identified as important signalling pathways for
      neurotrophins in PC12 cells. Our results establish GPR17 as a neurotrophic
      regulator for neuronal-like cells and suggest a possible interplay between
      endogenous uracil derivatives, cysLTs and NGF in the signalling pathways involved
      in neuronal survival and differentiation. They also represent the first direct
      demonstration, in a native system, that GPR17 can indeed be activated by uracil
      nucleotides and cysLTs, in line with what previously demonstrated in recombinant
      expression systems.

PMID- 20056145
TI  - Neurogenesis in mouse models of Alzheimer's disease.
AB  - The brains of the adult mouse and human possess neural stem cells (NSCs) that
      retain the capacity to generate new neurons through the process of neurogenesis.
      They share the same anatomical locations of stem cell niches in the brain, as
      well as the prominent feature of rostral migratory stream formed by neuroblasts
      migrating from the lateral ventricles towards the olfactory bulb. Therefore the
      mouse possesses some fundamental features that may qualify it as a relevant model
      for adult human neurogenesis. Adult born young hippocampal neurons in the mouse
      display the unique property of enhanced plasticity, and can integrate physically
      and functionally into existing neural circuits in the brain. Such crucial
      properties of neurogenesis may at least partially underlie the improved learning
      and memory functions observed in the mouse when hippocampal neurogenesis is
      augmented, leading to the suggestion that neurogenesis induction may be a novel
      therapeutic approach for diseases with cognitive impairments such as Alzheimer's
      disease (AD). Research towards this goal has benefited significantly from the use
      of AD mouse models to facilitate the understanding in the impact of AD pathology
      on neurogenesis. The present article reviews the growing body of controversial
      data on altered neurogenesis in mouse models of AD and attempts to assess their
      relative relevance to humans.

PMID- 20056146
TI  - Prediction of the in vitro intrinsic clearance determined in suspensions of human
      hepatocytes by using artificial neural networks.
AB  - Use of in vitro suspensions of human hepatocytes is currently accepted as one of
      the most promising tools for prediction of metabolic clearance in new drugs. The
      possibility of creating computational models based on this data may potentiate
      the early selection process of new drugs. We present an artificial neural network
      for modelling human hepatocyte intrinsic clearances (CL(int)) based only on
      calculated molecular descriptors. In vitro CL(int) data obtained in human
      hepatocytes suspensions was divided into a train group of 71 drugs for network
      optimization and a test group of another 18 drugs for early-stop and internal
      validation resulting in correlations of 0.953 and 0.804 for the train and test
      group respectively. The model applicability was tested with 112 drugs by
      comparing the in silico predicted CL(int) with the in vivo CL(int) estimated by
      the "well-stirred" model based on the in vivo hepatic clearance (CL(H)).
      Acceptable correlations were observed with r values of 0.508 and 63% of drugs
      within a 10-fold difference when considering blood binding in acidic drugs only.
      This model may be a valuable tool for prediction and simulation in the drug
      development process, allowing the in silico estimation of the human in vivo
      hepatic clearance.

PMID- 20056147
TI  - Silymarin suppress CD4+ T cell activation and proliferation: effects on NF-kappaB
      activity and IL-2 production.
AB  - Silymarin, a mixture of bioactive flavonolignans isolated from Silybum marianum,
      exhibits anti-carcinogenic, anti-inflammatory and cytoprotective effects. In this
      study, the in vitro immunomodulatory activity of silymarin was investigated using
      CD4+ splenocytes from C57/Bl6 mice. Proliferation assay revealed that silymarin,
      at 50 microM concentration, significantly inhibited CD4+ cells proliferation.
      ELISA analyses indicated that silymarin significantly inhibited IL-2 and IFN
      gamma production. Immunofluorescence staining performed on the mouse hybridoma T
      cell line (3DO) revealed a block of nuclear translocation of transcription factor
      kappaB (NF-kappaB), which is known to be responsible for IL-2 transcriptional
      activation. Moreover, silymarin inhibited p65/NF-kappaB phosphorylation in CD4+ T
      cell. These results suggest that silymarin is able to inhibit T cell activation
      and proliferation, notably acting on pathways of NF-kappaB
      activation/translocation.

PMID- 20056148
TI  - Evolutionary tabu search strategies for the simultaneous registration of multiple
      atomic structures in cryo-EM reconstructions.
AB  - A structural characterization of multi-component cellular assemblies is essential
      to explain the mechanisms governing biological function. Macromolecular
      architectures may be revealed by integrating information collected from various
      biophysical sources - for instance, by interpreting low-resolution electron
      cryomicroscopy reconstructions in relation to the crystal structures of the
      constituent fragments. A simultaneous registration of multiple components is
      beneficial when building atomic models as it introduces additional spatial
      constraints to facilitate the native placement inside the map. The high
      dimensional nature of such a search problem prevents the exhaustive exploration
      of all possible solutions. Here we introduce a novel method based on genetic
      algorithms, for the efficient exploration of the multi-body registration search
      space. The classic scheme of a genetic algorithm was enhanced with new genetic
      operations, tabu search and parallel computing strategies and validated on a
      benchmark of synthetic and experimental cryo-EM datasets. Even at a low level of
      detail, for example 35-40 A, the technique successfully registered multiple
      component biomolecules, measuring accuracies within one order of magnitude of the
      nominal resolutions of the maps. The algorithm was implemented using the Sculptor
      molecular modeling framework, which also provides a user-friendly graphical
      interface and enables an instantaneous, visual exploration of intermediate
      solutions.

PMID- 20056149
TI  - ALE meta-analysis of action observation and imitation in the human brain.
AB  - Over the last decade, many neuroimaging studies have assessed the human brain
      networks underlying action observation and imitation using a variety of tasks and
      paradigms. Nevertheless, questions concerning which areas consistently contribute
      to these networks irrespective of the particular experimental design and how such
      processing may be lateralized remain unresolved. The current study aimed at
      identifying cortical areas consistently involved in action observation and
      imitation by combining activation likelihood estimation (ALE) meta-analysis with
      probabilistic cytoarchitectonic maps. Meta-analysis of 139 functional magnetic
      resonance and positron emission tomography experiments revealed a bilateral
      network for both action observation and imitation. Additional subanalyses for
      different effectors within each network revealed highly comparable activation
      patterns to the overall analyses on observation and imitation, respectively,
      indicating an independence of these findings from potential confounds.
      Conjunction analysis of action observation and imitation meta-analyses revealed a
      bilateral network within frontal premotor, parietal, and temporo-occipital
      cortex. The most consistently rostral inferior parietal area was PFt, providing
      evidence for a possible homology of this region to macaque area PF. The
      observation and imitation networks differed particularly with respect to the
      involvement of Broca's area: whereas both networks involved a caudo-dorsal part
      of BA 44, activation during observation was most consistent in a more rostro
      dorsal location, i.e., dorsal BA 45, while activation during imitation was most
      consistent in a more ventro-caudal aspect, i.e., caudal BA 44. The present meta
      analysis thus summarizes and amends previous descriptions of the human brain
      networks related to action observation and imitation.

PMID- 20056151
TI  - Dynamic causal modelling of effective connectivity from fMRI: are results
      reproducible and sensitive to Parkinson's disease and its treatment?
AB  - Dynamic causal modelling (DCM) of functional magnetic resonance imaging (fMRI)
      data offers new insights into the pathophysiology of neurological disease and
      mechanisms of effective therapies. Current applications can be used both to
      identify the most likely functional brain network underlying observed data and
      estimate the networks' connectivity parameters. We examined the reproducibility
      of DCM in healthy subjects (young 18-48 years, n=27; old 50-80 years, n=15) in
      the context of action selection. We then examined the effects of Parkinson's
      disease (50-78 years, Hoehn and Yahr stage 1-2.5, n=16) and dopaminergic therapy.
      Forty-eight models were compared, for each of 90 sessions from 58 subjects. Model
      evidences clustered according to sets of structurally similar models, with high
      correlations over two sessions in healthy older subjects. The same model was
      identified as most likely in healthy controls on both sessions and in medicated
      patients. In this most likely network model, the selection of action was
      associated with enhanced coupling between prefrontal cortex and the pre
      supplementary motor area. However, the parameters for intrinsic connectivity and
      contextual modulation in this model were poorly correlated across sessions. A
      different model was identified in patients with Parkinson's disease after
      medication withdrawal. In "off" patients, action selection was associated with
      enhanced connectivity from prefrontal to lateral premotor cortex. This accords
      with independent evidence of a dopamine-dependent functional disconnection of the
      SMA in Parkinson's disease. Together, these results suggest that DCM model
      selection is robust and sensitive enough to study clinical populations and their
      pharmacological treatment. For critical inferences, model selection may be
      sufficient. However, caution is required when comparing groups or drug effects in
      terms of the connectivity parameter estimates, if there are significant posterior
      covariances among parameters.

PMID- 20056150
TI  - A group independent component analysis of covert verb generation in children: a
      functional magnetic resonance imaging study.
AB  - Semantic language skills are an integral part of early childhood language
      development. The semantic association between verbs and nouns constitutes an
      important building block for the construction of sentences. In this large-scale
      functional magnetic resonance imaging (fMRI) study, involving 336 subjects
      between the ages of 5 and 18 years, we investigated the neural correlates of
      covert verb generation in children. Using group independent component analysis
      (ICA), seven task-related components were identified including the mid-superior
      temporal gyrus, the most posterior aspect of the superior temporal gyrus, the
      parahippocampal gyrus, the inferior frontal gyrus, the angular gyrus, and medial
      aspect of the parietal lobule (precuneus/posterior cingulate). A highly left
      lateralized component was found including the medial temporal gyrus, the frontal
      gyrus, the inferior frontal gyrus, and the angular gyrus. The associated
      independent component (IC) time courses were analyzed to investigate
      developmental changes in the neural elements supporting covert verb generation.
      Observed age effects may either reflect specific local neuroplastic changes in
      the neural substrates supporting language or a more global transformation of
      neuroplasticity in the developing brain. The results are analyzed and presented
      in the framework of two theoretical models for neurocognitive brain development.
      In this context, group ICA of fMRI data from our large sample of children aged 5
      18 years provides strong evidence in support of the regionally weighted model for
      cognitive neurodevelopment of language networks.

PMID- 20056152
TI  - Brain mechanisms for representing what another person sees.
AB  - We used functional magnetic resonance imaging (fMRI) and a naturalistic joint
      attention scenario to evaluate two, alternative hypotheses concerning the social
      brain. The first, Content Specific Attribution hypothesis, was that core regions
      previously identified as being involved in social cognition also participate in
      representing the contents of another mind. The second, Dual Role hypothesis, was
      that extrastriate, category-specific visual regions respond to a visible stimulus
      of a specific category and to the same stimulus occluded, but when it appears to
      be the focus of another person's visual attention. Participants viewed category
      specific stimuli (Place and Body images) to localize the extrastriate body area
      (EBA) and parahippocampal place area (PPA). Then, they observed a computerized
      character viewing each stimulus category, occluded from the participant's view.
      In support of the Content Specific Attribution hypothesis, whole-brain analyses
      revealed that viewing someone else looking at an occluded picture of a body
      activated brain regions previously associated with components of social cognition
      more than viewing someone else looking at an occluded picture of a place. Counter
      to the Dual Role hypothesis, functional region of interest (ROI) analyses
      revealed that the EBA and PPA were not clearly involved in representing what the
      character was seeing.

PMID- 20056153
TI  - Cortical response to social interaction is affected by gender.
AB  - The ability of humans to predict and explain other people's actions is of immense
      value for adaptive behavior and nonverbal communication. Gender differences are
      often evident in the comprehension of social signals, but the underlying
      neurobiological basis for these differences is unclear. Combining visual
      psychophysics with an analysis of neuromagnetic activity, we assessed gender
      effects on the induced oscillatory response to visual social interaction revealed
      by motion. A robust difference in the induced gamma response was found between
      females and males over the left prefrontal cortex, a region implicated in
      perceptual decision making. The induced gamma neuromagnetic response peaked
      earlier in females than in males. Moreover, it appears that females anticipate
      social interaction predicting others' actions ahead of their realization, whereas
      males require accumulation of more sensory evidence for proper social decisions.
      The findings reflect gender-dependent modes in cortical processing of visually
      acquired social information. Contrary to popular wisdom, the outcome of this
      study indicates that gender effects are not evident in the neural circuitry
      underpinning visual social perception, but in the regions engaged in perceptual
      decision making.

PMID- 20056154
TI  - Relating structural and functional anomalous connectivity in the aging brain via
      neural mass modeling.
AB  - The structural changes that arise as the brain ages influence its functionality.
      In many cases, the anatomical degradation simply leads to normal aging. In
      others, the neurodegeneration is large enough to cause neurological disorders
      (e.g. Alzheimer's disease). Structure and function can be both currently measured
      using noninvasive techniques, such as magnetic resonance imaging (MRI) and
      electroencephalography (EEG) respectively. However, a full theoretical scheme
      linking structural and functional degradation is still lacking. Here we present a
      neural mass model that aims to bridge both levels of description and that
      reproduces experimentally observed multichannel EEG recordings of alpha rhythm in
      young subjects, healthy elderly subjects, and patients with mild cognitive
      impairment. We focus our attention in the dominant frequency of the signals at
      different electrodes and in the correlation between specific electrode pairs,
      measured via the phase-lag index. Our model allows us to study the influence of
      different structural connectivity pathways, independently of each other, on the
      normal and aberrantly aging brain. In particular, we study in detail the effect
      of the thalamic input on specific cortical regions, the long-range connectivity
      between cortical regions, and the short-range coupling within the same cortical
      area. Once the influence of each type of connectivity is determined, we
      characterize the regions of parameter space compatible with the EEG recordings of
      the populations under study. Our results show that the different types of
      connectivity must be fine-tuned to maintain the brain in a healthy functioning
      state independently of its age and brain condition.

PMID- 20056155
TI  - Impaired top-down processes in schizophrenia: a DCM study of ERPs.
AB  - Perception is not simply based on a hierarchical organization of the brain; it
      arises from an interplay between inputs from the environment and internal
      predictions of these inputs. It is an active process which involves an
      interaction between bottom-up information coming from the senses and feedback
      connections coming from higher-order cortical areas. In our experiment, we use
      the hollow-mask illusion to investigate the strength of top-down processes in
      schizophrenic patients and healthy controls. By using dynamic causal modelling
      (DCM) on functional magnetic resonance tomography (fMRI) data, we have presented
      evidence to suggest that patients with schizophrenia are less constrained by top
      down processes during perception (Dima, D., Roiser, J.P., Dietrich, D.E.,
      Bonnemann, C., Lanfermann, H., Emrich, H.M., Dillo, W., 2009. Understanding why
      patients with schizophrenia do not perceive the hollow-mask illusion using
      dynamic causal modeling. Neuroimage 46, 1180-1186). In this study, we re-address
      this issue by using DCM on event-related potentials (ERPs) data. Our aim was to
      validate our previous findings by conducting the same connectivity analysis--DCM-
      on data obtained from a different neuroimaging method. Our results confirm our
      initial hypothesis that top-down influences are constrained in schizophrenia,
      especially in perceptual tasks that require top-down control, like the hollow
      mask illusion.

PMID- 20056156
TI  - Optimized beamforming for simultaneous MEG and intracranial local field potential
      recordings in deep brain stimulation patients.
AB  - Insight into how brain structures interact is critical for understanding the
      principles of functional brain architectures and may lead to better diagnosis and
      therapy for neuropsychiatric disorders. We recorded, simultaneously,
      magnetoencephalographic (MEG) signals and subcortical local field potentials
      (LFP) in a Parkinson's disease (PD) patient with bilateral deep brain stimulation
      (DBS) electrodes in the subthalamic nucleus (STN). These recordings offer a
      unique opportunity to characterize interactions between the subcortical
      structures and the neocortex. However, high-amplitude artefacts appeared in the
      MEG. These artefacts originated from the percutaneous extension wire, rather than
      from the actual DBS electrode and were locked to the heart beat. In this work, we
      show that MEG beamforming is capable of suppressing these artefacts and quantify
      the optimal regularization required. We demonstrate how beamforming makes it
      possible to localize cortical regions whose activity is coherent with the STN
      LFP, extract artefact-free virtual electrode time-series from regions of interest
      and localize cortical areas exhibiting specific task-related power changes. This
      furnishes results that are consistent with previously reported results using
      artefact-free MEG data. Our findings demonstrate that physiologically meaningful
      information can be extracted from heavily contaminated MEG signals and pave the
      way for further analysis of combined MEG-LFP recordings in DBS patients.

PMID- 20056157
TI  - The role of the right inferior frontal gyrus: inhibition and attentional control.
AB  - There is growing interest regarding the role of the right inferior frontal gyrus
      (RIFG) during a particular form of executive control referred to as response
      inhibition. However, tasks used to examine neural activity at the point of
      response inhibition have rarely controlled for the potentially confounding
      effects of attentional demand. In particular, it is unclear whether the RIFG is
      specifically involved in inhibitory control, or is involved more generally in the
      detection of salient or task relevant cues. The current fMRI study sought to
      clarify the role of the RIFG in executive control by holding the stimulus
      conditions of one of the most popular response inhibition tasks-the Stop Signal
      Task-constant, whilst varying the response that was required on reception of the
      stop signal cue. Our results reveal that the RIFG is recruited when important
      cues are detected, regardless of whether that detection is followed by the
      inhibition of a motor response, the generation of a motor response, or no
      external response at all.

PMID- 20056158
TI  - High-dimensional pattern regression using machine learning: from medical images
      to continuous clinical variables.
AB  - This paper presents a general methodology for high-dimensional pattern regression
      on medical images via machine learning techniques. Compared with pattern
      classification studies, pattern regression considers the problem of estimating
      continuous rather than categorical variables, and can be more challenging. It is
      also clinically important, since it can be used to estimate disease stage and
      predict clinical progression from images. In this work, adaptive regional feature
      extraction approach is used along with other common feature extraction methods,
      and feature selection technique is adopted to produce a small number of
      discriminative features for optimal regression performance. Then the Relevance
      Vector Machine (RVM) is used to build regression models based on selected
      features. To get stable regression models from limited training samples, a
      bagging framework is adopted to build ensemble basis regressors derived from
      multiple bootstrap training samples, and thus to alleviate the effects of
      outliers as well as facilitate the optimal model parameter selection. Finally,
      this regression scheme is tested on simulated data and real data via cross
      validation. Experimental results demonstrate that this regression scheme achieves
      higher estimation accuracy and better generalizing ability than Support Vector
      Regression (SVR).

PMID- 20056159
TI  - Neural substrates of phonological selection for Japanese character Kanji based on
      fMRI investigations.
AB  - Japanese and Chinese both share the same ideographic/logographic character
      system. How these characters are processed, however, is inherently different for
      each language. We harnessed the unique property of homophone judgment in Japanese
      kanji to provide an analogous Chinese condition using event-related functional
      magnetic resonance imaging (fMRI) in 33 native Japanese speakers. We compared two
      types of kanji: (1) kanji that usually evokes only one pronunciation to Japanese
      speakers, which is representative of most Chinese characters (monophonic
      character); (2) kanji that evoked multiple pronunciation candidates, which is
      typical in Japanese kanji (heterophonic character). Results showed that character
      pairs with multiple sound possibilities increased activation in posterior regions
      of the left, middle and inferior frontal gyri (MFG and IFG), the bilateral
      anterior insulae, and the left anterior cingulate cortex as compared with those
      of kanji with only one sound. The activity seen in the MFG, dorsal IFG, and
      ventral IFG in the left posterior lateral prefrontal cortex, which was thought to
      correspond with language components of orthography, phonology, and semantics,
      respectively, was discussed in regards to their potentially important roles in
      information selection among competing sources of the components. A comparison
      with previous studies suggested that detailed analyses of activation in these
      language areas could explain differences between Japanese and Chinese, such as a
      greater involvement of the prefrontal language production regions for Japanese,
      whereas, for Chinese there is more phonological processing of inputs in the
      superior temporal gyrus.

PMID- 20056160
TI  - Sulcal set optimization for cortical surface registration.
AB  - Flat mapping based cortical surface registration constrained by manually traced
      sulcal curves has been widely used for inter subject comparisons of
      neuroanatomical data. Even for an experienced neuroanatomist, manual sulcal
      tracing can be quite time consuming, with the cost increasing with the number of
      sulcal curves used for registration. We present a method for estimation of an
      optimal subset of size N(C) from N possible candidate sulcal curves that
      minimizes a mean squared error metric over all combinations of N(C) curves. The
      resulting procedure allows us to estimate a subset with a reduced number of
      curves to be traced as part of the registration procedure leading to optimal use
      of manual labeling effort for registration. To minimize the error metric we
      analyze the correlation structure of the errors in the sulcal curves by modeling
      them as a multivariate Gaussian distribution. For a given subset of sulci used as
      constraints in surface registration, the proposed model estimates registration
      error based on the correlation structure of the sulcal errors. The optimal subset
      of constraint curves consists of the N(C) sulci that jointly minimize the
      estimated error variance for the subset of unconstrained curves conditioned on
      the N(C) constraint curves. The optimal subsets of sulci are presented and the
      estimated and actual registration errors for these subsets are computed.

PMID- 20056161
TI  - Bayesian spatiotemporal model of fMRI data using transfer functions.
AB  - This research describes a new Bayesian spatiotemporal model to analyse BOLD fMRI
      studies. In the temporal dimension, we describe the shape of the hemodynamic
      response function (HRF) with a transfer function model. The spatial continuity
      and local homogeneity of the evoked responses are modelled by a Gaussian Markov
      random field prior on the parameter indicating activations. The proposal
      constitutes an extension of the spatiotemporal model presented in a previous
      approach [Quiros, A., Montes Diez, R. and Gamerman, D., 2010. Bayesian
      spatiotemporal model of fMRI data, Neuroimage, 49: 442-456], offering more
      flexibility in the estimation of the HRF and computational advantages in the
      resulting MCMC algorithm. Simulations from the model are performed in order to
      ascertain the performance of the sampling scheme and the ability of the posterior
      to estimate model parameters, as well as to check the model sensitivity to signal
      to noise ratio. Results are shown on synthetic data and on a real data set from a
      block-design fMRI experiment.

PMID- 20056162
TI  - Noninvasive visualization of human dopamine dynamics from PET images.
AB  - We recently introduced strategies for extracting temporal patterns of brain
      dopamine fluctuations from dynamic positron emission tomography (PET) data using
      the tracer [11C]-raclopride. Each of our methods yields a collection of time
      concentration curves for endogenous dopamine. Given a spatially dense collection
      of curves (i.e., one at every voxel in a region of interest), we produce image
      volumes of dopamine (DA) concentration, DA(X, t), at multiple voxel locations and
      each time-frame. The volume over time-frames constitutes a 4D dataset that can be
      thought of as a DA "movie". There are a number of ways to visualize such data.
      Viewing cine loops of a slice through the DA volume is one way. Creating images
      of dopamine peak-time, Tpeak(X), derived from a movie, is another. Each
      visualization may reveal spatio-temporal patterns of neurotransmitter activity
      heretofore unobservable. We conducted an initial validation experiment in which
      identical DA responses were induced by an identical task, initiated at different
      times by the same subject, in two separate PET scans. A comparison of the
      resulting Tpeak(X) images revealed a large contiguous cluster of striatal voxels,
      on each side, whose DA timing was consistent with the relative timing of the
      tasks. Hence, the DA movies and their respective peak-time images were shown to
      be new types of functional images that contain bonafide timing information about
      a neurotransmitter's response to a stimulus.

PMID- 20056163
TI  - The change in cerebrovascular reactivity between 3 T and 7 T measured using
      graded hypercapnia.
AB  - Mapping cerebrovascular reactivity (CVR) to hypercapnia is important both
      clinically and for improved understanding of the haemodynamic properties of the
      BOLD effect. In this work, BOLD/R2 CVR was investigated by using a device which
      provided small, repeatable and stable steps in PETCO2, whilst maintaining a
      steady PETO2 level. Significant CVR was observed in both grey and white matter at
      both 3 and 7 T, whilst an approximately linear relationship found between R2 CVR
      and field strength has implications for BOLD models and calibration. Grey matter
      R2 CVR was 0.066+/-0.004 s(-1) mm Hg(-1) at 3 T and 0.141+/-0.008 s(-1) mm Hg(-1)
      at 7 T. White matter R2 CVR was 0.021+/-0.003 s(-1) mm Hg(-1) at 3 T and 0.040+/
      0.007 s(-1) mm Hg(-1) at 7 T.

PMID- 20056164
TI  - Phylogeography of the armadillo Chaetophractus villosus (Dasypodidae Xenarthra):
      post-glacial range expansion from Pampas to Patagonia (Argentina).
AB  - We report a phylogeographic study of Chaetophractus villosus populations in
      Argentina. Control Region (CR) sequences (484 bp) were obtained for 76 C.
      villosus from 20 locations across the species whole distribution range. Seventeen
      new haplotypes were identified. The highest genetic variation and the earliest
      fossils were found in the Pampean Region, thus appearing as the most probable
      area of origin of the species. A general pattern of Contiguous Range Expansion
      (CRE) was revealed by Nested Clade Analysis (NCA) supported by mismatch analysis
      and Fu's test. The Pampean Region would have been the pre-expansion area, while
      Patagonia would have been the main dispersal route of contiguous expansion,
      possibly after the Pleistocenic glaciations.

PMID- 20056165
TI  - Resolved hepatitis B virus infection is not associated with worse outcome after
      allogeneic hematopoietic stem cell transplantation.
AB  - Serologic evidence of resolved hepatitis B virus (HBV) infection has been
      associated with reactivation of hepatitis after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT), but the true impact of this finding is unknown.
      We conducted a retrospective matched-control analysis of the outcomes of 76
      patients with positive HBV core antibody (HBcAb) and negative HBV surface antigen
      (HBsAg) at the time of allo-HSCT for hematologic or solid malignancies. Control
      patients (matched controls), with negative serology for HBV and other viral
      hepatitides, were matched by age, diagnosis, disease risk, intensity of
      conditioning regimen, and donor type. In addition, the HBcAb-positive patients
      and all seronegative patients (all controls, n = 1858) undergoing transplantation
      during the same period were compared to adjust for other confounding effects.
      Patient characteristics and baseline hepatic function studies were similar in the
      HBcAb-positive and matched control groups. The cumulative incidence of hepatitis
      B reactivation (defined as the emergence of HBsAg in serum) was 11.6% at 3 years.
      There were no significant differences in overall survival, relapse, nonrelapse
      mortality, and incidence of acute graft-versus-host disease between the HBcAb
      positive and control groups. Our data suggest that seropositivity for HBcAb and
      seronegativity for HBsAg at the time of transplantation does not seem to
      adversely affect outcome after allo-HSCT.

PMID- 20056166
TI  - Monoclonal antibodies against nucleoside triphosphate hydrolase-II can reduce the
      replication of Toxoplasma gondii.
AB  - Nucleoside triphosphate hydrolase (NTPase) is an abundant protein secreted by the
      obligate protozoan parasite Toxoplasma gondii, which has a wide specificity
      toward NTP. In the present study, two monoclonal antibodies (mAbs, MNT1 and MNT2)
      against recombinant T. gondii NTPase-II (rTgNTPase-II) were developed. Western
      blot analysis displayed that these two mAbs can recognize specifically rTgNTPase
      II as well as a 63kDa molecule in tachyzoites soluble antigens that corresponded
      to native NTPase-II. T. gondii tachyzoites pretreated with two mAbs were observed
      under Confocal Laser Microscope and a specific reaction was displayed on
      tachyzoites after indirect fluorescence antibody test (IFAT). When COS-7 cells
      were co-cultured with tachyzoites pretreated with two mAbs, the number of
      intracellular parasites per infected cell was significantly decreased compared
      with the control. Furthermore, incubation of T. gondii tachyzoites with two mAbs
      can inhibit NTPase activity in the presence of dithiothreitol, which hinted that
      the reduction of tachyzoite replication might be owing to the inhibition of
      NTPase-II by the mAbs. The passive immunization test indicated that the
      transferred mAbs can significantly prolong the survival time of challenge
      infected mice. Taken together, we concluded that the mAbs against NTPase-II can
      reduce the replication of T. gondii and have a crucial effect on the protection
      of host from T. gondii infection.

PMID- 20056167
TI  - Obese and anorexic yeasts: experimental models to understand the metabolic
      syndrome and lipotoxicity.
AB  - Lipotoxicity is the pathological consequence of lipid overflow in non-adipose
      tissue, mediated through reactive lipid moieties which may even lead to lipid
      induced cell death (lipoapoptosis). This derailment of cellular and organismal
      fat homeostasis is the consequence of obesity due to continued over-feeding, and
      contributes substantially to the pathogenesis of insulin resistance, type 2
      diabetes mellitus and cardiovascular disease, which are all components of the
      metabolic syndrome. Now, does yeast, a single-celled eukaryote, ever suffer from
      the metabolic syndrome and what can we potentially learn from studies in this
      organism about the underlying molecular mechanism that lead to lipid-associated
      pathologies in human cells? In this review I will summarize the remarkably
      conserved metabolic and regulatory processes relevant to establishing cellular
      energy and lipid homeostasis, as well as recent findings that provide detailed
      insights into the molecular mechanisms underlying fat-induced cellular
      malfunction and cell death, with potential implications also for mammalian cells.

PMID- 20056168
TI  - Modulation of plasma TG lipolysis by Angiopoietin-like proteins and GPIHBP1.
AB  - There is evidence that elevated plasma triglycerides (TG) serve as an independent
      risk factor for coronary heart disease. Plasma TG levels are determined by the
      balance between the rate of production of chylomicrons and VLDL in intestine and
      liver, respectively, and their rate of clearance in peripheral tissues. Lipolytic
      processing of TG-rich lipoproteins is mediated by the enzyme lipoprotein lipase
      (LPL), which is tethered to the capillary endothelium via heparin sulphate
      proteoglycans. In recent years the Angiopoietin-like proteins ANGPTL3 and ANGPTL4
      have emerged as novel modulators of LPL activity. Studies in transgenic animals
      supported by in vitro experiments have demonstrated that ANGPTL3 and ANGPTL4
      impair plasma TG clearance by inhibiting LPL activity. In humans, genetic
      variation within the ANGPTL3 and ANGPTL4 genes contributes to variation in plasma
      TG and HDL levels, thereby validating the importance of ANGPTLs in the regulation
      of lipoprotein metabolism in humans. Combined with the discovery of GPIHBP1 as a
      likely LPL anchor, these findings have led to a readjustment of the mechanism of
      LPL function. This review provides an overview of our current understanding of
      the role and regulation of ANGPTL3, ANGPTL4 and GPIHBP1, and places the newly
      acquired knowledge in the context of the established function and mechanism of
      LPL-mediated lipolysis.

PMID- 20056169
TI  - Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome--an
      allostatic perspective.
AB  - While the link between obesity and type 2 diabetes is clear on an epidemiological
      level, the underlying mechanism linking these two common disorders is not as
      clearly understood. One hypothesis linking obesity to type 2 diabetes is the
      adipose tissue expandability hypothesis. The adipose tissue expandability
      hypothesis states that a failure in the capacity for adipose tissue expansion,
      rather than obesity per se is the key factor linking positive energy balance and
      type 2 diabetes. All individuals possess a maximum capacity for adipose expansion
      which is determined by both genetic and environmental factors. Once the adipose
      tissue expansion limit is reached, adipose tissue ceases to store energy
      efficiently and lipids begin to accumulate in other tissues. Ectopic lipid
      accumulation in non-adipocyte cells causes lipotoxic insults including insulin
      resistance, apoptosis and inflammation. This article discusses the links between
      adipokines, inflammation, adipose tissue expandability and lipotoxicity. Finally,
      we will discuss how considering the concept of allostasis may enable a better
      understanding of how diabetes develops and allow the rational design of new anti
      diabetic treatments.

PMID- 20056170
TI  - Pharmacological and toxicological target organelles and safe use of single-walled
      carbon nanotubes as drug carriers in treating Alzheimer disease.
AB  - Identification of pharmacological and toxicological profiles is of critical
      importance for the use of nanoparticles as drug carriers in nanomedicine and for
      the biosafety evaluation of environmental nanoparticles in nanotoxicology. Here
      we show that lysosomes are the pharmacological target organelles for single
      walled carbon nanotubes (SWCNTs) and that mitochondria are the target organelles
      for their cytotoxicity. The gastrointestinally absorbed SWCNTs were
      lysosomotropic but also entered mitochondria at large doses. Genes encoding
      phosphoinositide-3-kinase and lysosomal-associated membrane protein 2 were
      involved in such an organelle preference. SWCNT administration resulted in
      collapse of mitochondrial membrane potentials, giving rise to overproduction of
      reactive oxygen species, leading to damage of mitochondria, which was followed by
      lysosomal and cellular injury. Based on the dosage differences in target
      organelles, SWCNTs were successfully used to deliver acetylcholine into brain for
      treatment of experimentally induced Alzheimer disease with a moderate safety
      range by precisely controlling the doses, ensuring that SWCNTs preferentially
      enter lysosomes, the target organelles, and not mitochondria, the target
      organelles for SWCNT cytotoxicity. FROM THE CLINICAL EDITOR: Single wall carbon
      nanotubes (SWCNT) could make excellent targeted delivery systems for
      pharmaceuticals. Inside the cells, lysosomes are the pharmacological target
      organelles of SWCNT, but in large doses mitochondria also take up SWCNT and
      mitochondrial toxicity becomes the reason for overall toxicity of this approach.
      In this paper, SWCNT were successfully used to deliver acetylcholine in
      Alzheimer's disease brains with high safety range by controlling the doses to
      ensure lysosomal but not mitochondrial targeting.

PMID- 20056171
TI  - Analysis of proton exchange kinetics with time-dependent exchange rate.
AB  - Mass spectrometry is used to probe the kinetics of hydrogen-deuterium exchange in
      lysozyme in pH 5, 6 and 7.4. An analysis based on a Verhulst growth model is
      proposed and effectively applied to the kinetics of the hydrogen exchange. The
      data are described by a power-like function which is based on a time-dependence
      of the exchange rate. Experimental data ranging over many time scales is
      considered and accurate fits of a power-like function are obtained. Results of
      fittings show correlation between faster hydrogen-deuterium exchange and increase
      of pH. Furthermore a model is presented that discriminates between easily
      exchangeable hydrogens (located in close proximity to the protein surface) and
      those protected from the exchange (located in the protein interior). A possible
      interpretation of the model and its biological significance are discussed.

PMID- 20056172
TI  - Kinetic and biochemical properties of high and low redox potential laccases from
      fungal and plant origin.
AB  - The electrochemical studies of laccase-mediator systems are aimed at
      understanding the mechanism of their redox transformation and their efficiency in
      both homogeneous and heterogeneous reactions; this topic has paramount
      application spanning from bleaching of paper pulp and the enzymatic degradation
      of lignin to the biosensors and biofuel cell development. In this paper four
      different laccases from Trametes hirsuta (ThL), Trametes versicolor (TvL),
      Melanocarpus albomyces (r-MaL) and Rhus vernicifera (RvL) were characterized from
      both biochemical and electrochemical points of view. Two of them (TvL and ThL)
      are high redox potential and two (RvL and r-MaL) are low redox potential
      laccases. The outline of this work is focused on the determination of catalytic
      and bioelectrochemical properties of these four enzymes in homogenous solution as
      well as immobilized onto electrode surface in the presence of a set of different
      redox mediators. The results measured in the homogenous reaction system
      correlated well with those measured with the immobilized enzymes. In addition,
      they are in good agreement with those reported with reference techniques,
      suggesting that the electrochemical methods employed in this work can be applied
      well in place of the traditional techniques commonly used for the kinetic
      characterization of laccases. These results are also discussed in terms of the
      known amino acid sequences and three-dimensional (3D) structures of the laccases.

PMID- 20056173
TI  - Synthesis and properties of hydroxyapatite-containing porous titania coating on
      ultrafine-grained titanium by micro-arc oxidation.
AB  - Equal channel angular pressing results in ultrafine-grained (approximately 200
      500 nm) Ti with superior mechanical properties without harmful alloying elements,
      which benefits medical implants. To further improve the bioactivity of Ti
      surfaces, Ca/P-containing porous titania coatings were prepared on ultrafine
      grained and coarse-grained Ti by micro-arc oxidation (MAO). The phase
      identification, composition, morphology and microstructure of the coatings and
      the thermal stability of ultrafine-grained Ti during MAO were investigated
      subsequently. The amounts of Ca, P and the Ca/P ratio of the coatings formed on
      ultrafine-grained Ti were greater than those on coarse-grained Ti.
      Nanocrystalline hydroxyapatite and alpha-Ca(3)(PO(4))(2) phases appeared in the
      MAO coating formed on ultrafine-grained Ti for 20 min (E20). Incubated in a
      simulated body fluid, bone-like apatite was completely formed on the surface of
      E20 after 2 days, thus evidencing preferable bioactivity. Compared with initial
      ultrafine-grained Ti, the microhardness of the E20 substrate was reduced by 8% to
      2.9 GPa, which is considerably more than that of coarse-grained Ti (approximately
      1.5 GPa).

PMID- 20056174
TI  - Multi-functional P(3HB) microsphere/45S5 Bioglass-based composite scaffolds for
      bone tissue engineering.
AB  - Novel multi-functional P(3HB) microsphere/45S5 Bioglass-based composite scaffolds
      exhibiting potential for drug delivery were developed for bone tissue
      engineering. 45S5 Bioglass-based glass-ceramic scaffolds of high interconnected
      porosity produced using the foam-replication technique were coated with
      biodegradable microspheres (size<2 microm) made from poly(3-hydroxybutyrate),
      P(3HB), produced using Bacillus cereus SPV. A solid-in-oil-in-water emulsion
      solvent extraction/evaporation technique was used to produce these P(3HB)
      microspheres. A simple slurry-dipping method, using a 1 wt.% suspension of P(3HB)
      microspheres in water, dispersed by an ultrasonic bath, was used to coat the
      scaffold, producing a uniform microsphere coating throughout the three
      dimensional scaffold structure. Compressive strength tests confirmed that the
      microsphere coating slightly enhanced the scaffold mechanical strength. It was
      also confirmed that the microsphere coating did not inhibit the bioactivity of
      the scaffold when immersed in simulated body fluid (SBF) for up to 4 weeks. The
      hydroxyapatite (HA) growth rate on P(3HB) microsphere-coated 45S5 Bioglass
      composite scaffolds was very similar to that on the uncoated control sample,
      qualitatively indicating similar bioactivity. However, the surface topography of
      the HA surface layer was affected as shown by results obtained from white light
      interferometry. The roughness of the surface was much higher for the P(3HB)
      microsphere-coated scaffolds than for the uncoated samples, after 7 days in SBF.
      This feature would facilitate cell attachment and proliferation. Finally,
      gentamycin was successfully encapsulated into the P(3HB) microspheres to
      demonstrate the drug delivery capability of the scaffolds. Gentamycin release
      kinetics was determined using liquid chromatography-mass spectrometry. The
      release of the drug from the coated composite scaffolds was slow and controlled
      when compared to the observed fast and relatively uncontrolled drug release from
      the bone scaffold (without microsphere coating). Thus, this unique
      multifunctional bioactive composite scaffold has the potential to enhance cell
      attachment and to provide controlled delivery of relevant drugs for bone tissue
      engineering.

PMID- 20056175
TI  - Enhanced initial bone regeneration with inorganic polyphosphate-adsorbed
      hydroxyapatite.
AB  - Inorganic polyphosphate (poly(P)) can promote binding between fibroblast growth
      factors and their receptors and enhance osteoblastic cell differentiation and
      calcification. This study evaluated the possibilities for poly(P) adsorbed onto
      interconnected porous calcium hydroxyapatite (IP-CHA) as a new bone regeneration
      material. Prepared 1%, 5%, 25% and 50% poly(P)/IP-CHA composites showed the
      elution peak of poly(P) between 15 and 20 min, respectively, with the highest
      value from 50% poly(P)/IP-CHA in vitro. Histologically, at 1 week of placement
      into the femur of rabbits, granulation tissue had penetrated into the pores in
      all composites and IP-CHA as a control. In contrast, at 2 weeks of placement,
      newly formed lamellar bone was found in all groups, although a higher amount of
      bone regeneration was obviously formed in the 25% and 50% poly(P)/IP-CHA with a
      significantly higher value of bone regeneration ratio of 50% poly(P)/IP-CHA.
      These results indicate that 25% and 50% poly(P)/IP-CHA composites may enhance
      initial bone regeneration.

PMID- 20056176
TI  - Proteomics of trypanosomatids of human medical importance.
AB  - Leishmania spp., Trypanosoma cruzi, and Trypanosoma brucei are protozoan
      parasites that cause a spectrum of fatal human diseases around the world. Recent
      completion of the genomic sequencing of these parasites has enormous relevance to
      the study of their biology and the pathogenesis of the diseases they cause
      because it opens the door to high-throughput proteomic technologies. This review
      encompasses studies using diverse proteomic approaches with these organisms to
      describe and catalogue global protein profiles, reveal changes in protein
      expression during development, elucidate the subcellular localisation of gene
      products, and evaluate host-parasite interactions.

PMID- 20056177
TI  - Higher BMC and areal BMD in children and grandchildren of individuals with hip or
      knee replacement.
AB  - The relationship between aBMD and osteoarthritis (OA) remains unclear. We
      compared aBMD, BMC and bone size among children and grandchildren of Hutterites
      with hip or knee replacement (n=23 each) to children and grandchildren of age-
      and sex-matched controls (178 children and 267 grandchildren). There were no
      differences in anthropometric measures or activity levels between case and
      control probands, but femoral neck (FN) and spine (LS) aBMD and Z-scores were
      greater in cases than controls (0.89 vs. 0.80 g/cm2; 1.15 vs. 1.03 g/cm2; 1.5 vs.
      0.8; 2.4 vs. 1.2: all p<0.05). Hip, FN and LS aBMD (1.05 vs. 0.97, 0.92 vs. 0.84,
      1.15 vs. 1.03 g/cm2), BMC (34.1 vs. 32.0, 4.58 vs. 4.27, 69.5 vs. 62.4 g) and Z
      scores (1.0 vs. 0.4; 0.9 vs. 0.2; 1.3 vs. 0.2) were greater in daughters of cases
      than controls (hip BMC p=0.06, others p<0.05); there were no differences between
      sons. Grandchildren (aged 8-39 years) were categorized as growing (premenarcheal
      or male<14 years) or not growing (> or =2 years post-menarcheal or males> or =18
      years): 33 were not classified. Post-menarcheal, but not premenarcheal,
      granddaughters of cases had greater hip, FN and LS aBMD Z-scores (0.7 vs. -0.1;
      0.6 vs. -0.1; 0.8 vs. -0.3); greater hip and spine aBMD (1.03 vs. 0.95, 1.10 vs.
      0.98 g/cm2); greater femoral neck and spine BMC (4.77 vs. 4.21, 66.7 vs. 55.4 g);
      and greater spine bone area (60.7 vs. 56.6 cm2) compared to granddaughters of
      controls (all, p<0.05), which remained significant when height, weight, and age
      were included as covariates. Growing grandsons of cases were taller and heavier
      than control grandsons, and a greater hip aBMD among grandsons of cases (0.88 vs.
      0.76 g/cm2) was the only bone difference that remained significant after taking
      into account body size differences. Grandsons who were not growing had greater
      spine bone area (1.19 vs. 1.08 cm2) if their grandparent had OA compared to
      grandsons whose grandparents did not have OA. We speculate that there is a
      genetic basis for OA that leads to early differences in growth patterns among
      boys and greater peak bone mass and aBMD among girls.

PMID- 20056178
TI  - Polymorphisms in innate immunity genes and patients response to dendritic cell
      based HIV immuno-treatment.
AB  - Dendritic cells (DCs)-based vaccine was demonstrated to increase HIV specific
      cellular immune response; however, in some HIV-infected patients, the response to
      the vaccine resulted to be not effective. In order to understand if the outcome
      of the vaccination may be influenced by the host's genome and natural immunity,
      we studied the innate immune genome of HIV-infected patients previously
      vaccinated with DCs. We identified 15 SNPs potentially associated with the
      response to the immuno-treatment and two SNPs significantly associated with the
      modulation of the response to the DC vaccine: MBL2 rs10824792 and NOS1 rs693534.
      These two SNPs were also studied in different ethnic groups (Brazilians, African
      and Caucasian) of HIV-infected, exposed uninfected and unexposed uninfected
      subjects. The HIV positive Caucasian patients were also characterized by
      different disease progressions. Our findings suggest that, independently and/or
      in addition to other variables, the host's genome could significantly contribute
      to the modulation of the response to the DC vaccine.

PMID- 20056179
TI  - Immunity conferred by an experimental vaccine based on the recombinant PCV2 Cap
      protein expressed in Trichoplusia ni-larvae.
AB  - Porcine circovirus type 2 (PCV2) vaccination has been recently included as a
      measure to control postweaning multisystemic wasting syndrome (PMWS) in the
      field. Aiming to obtain a more affordable vaccine to be extensively implemented
      in the field, a highly efficient non-fermentative expression platform based on
      Trichoplusia ni (T. ni) larvae was used to produce a baculovirus-derived
      recombinant PCV2 Cap protein (rCap) for vaccine purposes. Vaccination of pigs
      with rCap induced solid protection against PCV2 experimental infection,
      inhibiting both the viremia and the viral shedding very efficiently. The
      protection afforded by the rCap vaccine strongly correlated with the induction of
      specific humoral immune responses, even in the presence of PCV2-specific maternal
      immunity, although cellular responses also seemed to play a partial role. In
      summary, we have shown that rCap expressed in T. ni larvae could be a cost
      effective PCV2 vaccine candidate to be tested under field conditions.

PMID- 20056180
TI  - Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year
      old Israeli children.
AB  - BACKGROUND: Despite its high worldwide morbidity and mortality, there is yet no
      licensed vaccine for shigellosis. We reported the safety and immunogenicity of
      Shigella O-specific polysaccharide-protein conjugates in adults and young
      children and efficacy of Shigella sonnei conjugate in young adults. METHODS: A
      double-blinded, randomized and vaccine-controlled Phase 3 evaluation of S. sonnei
      and Shigella flexneri 2a O-SP-rEPA conjugates, 25 microg, injected IM twice, 6
      weeks apart, into healthy 1-4 years old, is reported. The children were followed
      for 2 years by telephone every other week and stool cultures were obtained for
      each episode of acute diarrhea (> or =3 loose stools/day or a bloody/mucous
      stool). Sera were taken randomly from 10% of the participants for IgG anti-LPS
      and anti-carrier levels. RESULTS: Of the 2799 enrollees, 1433 received S. sonnei
      and 1366 S. flexneri 2a conjugates; 2699 (96.4%) completed the 2-year follow-up.
      Local reactions occurred in approximately 5% and approximately 4% had
      temperatures > or =38.0 degrees C lasting 1-2 days. There were no serious adverse
      events attributable to the vaccines. Of the 3295 stool cultures obtained, 125
      yielded S. sonnei and 21 S. flexneri 2a. Immunogenicity and efficacy were age
      related. The overall efficacy of the S. sonnei conjugate was 27.5%; 71.1%
      (P=0.043) in the 3-4 years old. The numbers for S. flexneri 2a were too few for
      meaningful analysis. Cross-protection by S. flexneri 2a for non-vaccine S.
      flexneri types was found, but the numbers were too few for statistical
      significance. There was an age-related rise of vaccine-specific IgG anti-LPS in
      both groups, peaking at about 10 weeks and declining thereafter, but remaining >
      or =4-fold higher than in the controls 2 years after the second dose.
      CONCLUSIONS: Shigella conjugates are safe and immunogenic in 1-4 years old. The
      S. sonnei conjugate elicited 71.1% efficacy in the 3-4 years old and can be
      predicted to be efficacious in individuals older than 3 years of age. These
      results urge studies with our improved conjugates.

PMID- 20056181
TI  - Meningococcal serogroup C polysaccharide specific memory B cells, directly
      enumerated by labeled polysaccharide, are not affected by age at vaccination.
AB  - The influence of age on the generation and persistence of specific memory B cells
      after vaccination with Neisseria meningitidis type C polysaccharide (MenC-PS)
      conjugate is unknown. MenC-PS-specific B cells could be directly enumerated by
      fluorochrome-labeled MenC-PS and flow cytometry in blood up to at least 4 years
      after vaccination, ranging from 0.01% to 0.78% of total B cells and did not
      correlate with age at vaccination. The percentage of MenC-specific memory B cells
      out of total memory B cells correlated with total MenC-specific B-cells and with
      frequencies of IgA(+) plus IgG(+) MenC-specific AbSC, but not with MenC-specific
      Ab.

PMID- 20056182
TI  - Heat denatured enzymatically inactive recombinant chlamydial protease-like
      activity factor induces robust protective immunity against genital chlamydial
      challenge.
AB  - We have shown previously that vaccination with recombinant chlamydial protease
      like activity factor (rCPAF) plus interleukin-12 as an adjuvant induces robust
      protective immunity against primary genital Chlamydia muridarum challenge in
      mice. Since CPAF is a protease, we compared the effects of enzymatically active
      and inactive (heat denatured) rCPAF to determine whether proteolytic activity is
      expendable for the induction of protective immunity against chlamydial challenge.
      Active, but not inactive, rCPAF immunization induced high levels of anti-active
      CPAF antibody, whereas both induced robust splenic CPAF-specific IFN-gamma
      production. Vaccination with active or inactive rCPAF induced enhanced vaginal
      chlamydial clearance as early as day 6 with complete resolution of infection by
      day 18, compared to day 30 in mock-vaccinated and challenged animals.
      Importantly, significant and comparable reductions in oviduct pathology were
      observed in active and inactive rCPAF-vaccinated mice compared to mock-vaccinated
      animals. Thus, rCPAF induced anti-chlamydial immunity is largely independent of
      enzymatic activity and secondary or higher order protein conformation.

PMID- 20056183
TI  - Longevity of protection in cattle following immunisation with emergency FMD A22
      serotype vaccine from the UK strategic reserve.
AB  - To determine the longevity of protective immunity following a single
      administration of emergency vaccine, and establish whether the immune response
      could be enhanced by increasing the antigen payload even further, cattle were
      vaccinated with an A22 Iraq vaccine containing either 1x antigen payload (field
      dose) or 5x antigen payload. Six months post-immunisation all cattle received a
      homologous virus challenge. The magnitude of the virus neutralising antibody
      response elicited was consistent with the response to similarly formulated A
      serotype vaccines with a PD(50) greater than 32. All the vaccinated cattle,
      regardless of antigen payload, were protected from clinical disease following
      challenge although some cattle in both groups became sub-clinically infected. We
      conclude that immunisation with a single inoculation of vaccine from the UK
      emergency reserve can protect cattle from clinical disease for at least 6 months
      post-vaccination and that a boost may be unnecessary in an outbreak situation.
      Some animals may become sub-clinically infected but this is likely to be
      dependent on the severity of challenge. The study confirmed that a booster at 21
      days post-vaccination was not necessary to maintain a cell-mediated response in
      cattle for 6 months. No increased benefits were recognised by increasing the
      antigen payload of this vaccine 5x.

PMID- 20056184
TI  - Intranasal immunization with Leish-111f induces IFN-gamma production and protects
      mice from Leishmania major infection.
AB  - The mucosal vaccination is a non-invasive alternative approach for not only
      mucosal pathogens but also parenteral pathogens, since it induces both mucosal
      and systemic immunoreactions. The purpose of this study was to evaluate the
      application of intranasal (i.n.) immunization with a recombinant leishmanial
      protein against Leishmania infection. BALB/c mice were i.n. administered 1-3
      times with Leish-111f plus cholera toxin (CT) adjuvant (Leish-111f/CT).
      Splenocytes from i.n. immunized mice produced high level of IFN-gamma but not IL
      4 in response to Leish-111f. When infected with 1x10(6) of Leishmania major
      promastigotes 2 weeks after the final administration, lesion development was
      completely controlled in all mice i.n. administered with Leish-111f/CT. Mice i.n.
      administered with Leish-111f alone showed neither cytokine productions nor lesion
      control even after 6 administrations, suggesting the importance of CT adjuvant.
      This report demonstrated for the first time that i.n. administration of a
      recombinant leishmanial protein induces Th1 type immunity and protects mice from
      Leishmania infection.

PMID- 20056185
TI  - Rift Valley fever virus subunit vaccines confer complete protection against a
      lethal virus challenge.
AB  - Rift Valley fever virus (RVFV) is an emerging mosquito-borne virus causing
      significant morbidity and mortality in livestock and humans. Rift Valley fever is
      endemic in Africa, but also outside this continent outbreaks have been reported.
      Here we report the evaluation of two vaccine candidates based on the viral Gn and
      Gc envelope glycoproteins, both produced in a Drosophila insect cell expression
      system. Virus-like particles (VLPs) were generated by merely expressing the Gn
      and Gc glycoproteins. In addition, a soluble form of the Gn ectodomain was
      expressed and affinity-purified from the insect cell culture supernatant. Both
      vaccine candidates fully protected mice from a lethal challenge with RVFV.
      Importantly, absence of the nucleocapsid protein in either vaccine candidate
      facilitates the differentiation between infected and vaccinated animals using a
      commercial recombinant nucleocapsid protein-based indirect ELISA.

PMID- 20056186
TI  - Predictors of HPV vaccine uptake among women aged 19-26: importance of a
      physician's recommendation.
AB  - Among insured women, aged 19-26 years, those who discussed the HPV vaccine with
      their physician and received a recommendation were overwhelmingly more likely to
      be vaccinated. Student status and perception of the personal importance of
      vaccination were also predictive of vaccination. The strength of the physician's
      recommendation played a significant role in the decision to be vaccinated,
      resulting in a 4-fold greater likelihood of vaccination when women received a
      strong recommendation versus one that was not strong. Health care providers
      should be well-informed about HPV vaccination and recognize that the strength of
      their recommendation to patients will foster appropriate uptake.

PMID- 20056187
TI  - Antibody persistence six years after two doses of combined hepatitis A and B
      vaccine.
AB  - Persistent immunity to hepatitis A and hepatitis B antibodies six years after
      vaccination of adolescents (aged 12-15 years) with a combined hepatitis A and B
      (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed.
      Yearly (Year-2-6) serum samples were tested for anti-HAV and anti-HBs using EIA.
      Subjects with anti-HBs concentrations <10 mIU/mL (14/23) at Year-5 or Year-6,
      received an additional HBV vaccine dose approximately 12 months after Year-6.
      Blood samples were collected pre-booster and 1 month post-booster to assess
      booster response. 240 subjects were vaccinated in the study; at Year-6, data were
      available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9%
      (39/42; 0, 12 month) of subjects had anti-HBs concentrations > or = 10 mIU/mL.
      All but one of the 14 boosted subjects responded to the additional HBV vaccine
      dose with anti-HBs concentrations > or = 100 mIU/mL. All seroconverted subjects
      who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced
      number of doses and similar long-term persistence of immunity make the 0, 6 month
      and 0, 12 month schedule preferable for immunization against HAV/HBV in this
      population.

PMID- 20056188
TI  - Engineering filamentous phage carriers to improve focusing of antibody responses
      against peptides.
AB  - The filamentous bacteriophage are highly immunogenic particles that can be used
      as carrier proteins for peptides and presumably other haptens and antigens. Our
      previous work demonstrated that the antibody response was better focused against
      a synthetic peptide if it was conjugated to phage as compared to the classical
      carrier, ovalbumin. We speculated that this was due, in part, to the relatively
      low surface complexity of the phage. Here, we further investigate the phage as an
      immunogenic carrier, and the effect reducing its surface complexity has on the
      antibody response against peptides that are either displayed as recombinant
      fusions to the phage coat or are chemically conjugated to it. Immunodominant
      regions of the minor coat protein, pIII, were removed from the phage surface by
      excising its N1 and N2 domains (Delta3 phage variant), whereas immunodominant
      epitopes of the major coat protein, pVIII, were altered by reducing the charge of
      its surface-exposed N-terminal residues (Delta8 phage variant). Immunization of
      mice revealed that the Delta3 variant was less immunogenic than wild-type (WT)
      phage, whereas the Delta8 variant was more immunogenic. The immunogenicity of two
      different peptides was tested in the context of the WT and Delta3 phage in two
      different forms: (i) as recombinant peptides fused to pVIII, and (ii) as
      synthetic peptides conjugated to the phage surface. One peptide (MD10) in its
      recombinant form produced a stronger anti-peptide antibody response fused to the
      WT carrier compared to the Delta3 phage carrier, and did not elicit a detectable
      anti-peptide response in its synthetic form conjugated to either phage carrier.
      This trend was reversed for a different peptide (4E10(L)), which did not produce
      a detectable anti-peptide antibody response as a recombinant fusion; yet, as a
      chemical conjugate to Delta3 phage, but not WT phage, it elicited a highly
      focused anti-peptide antibody response that exceeded the anti-carrier response by
      approximately 65-fold. The results suggest that focusing of the antibody response
      against synthetic peptides can be improved by decreasing the antigenic complexity
      of the phage surface.

PMID- 20056189
TI  - Long-term complications and risk of other serious infections following invasive
      Haemophilus influenzae serotype b disease in vaccinated children.
AB  - This study describes the long-term complications in children with Haemophilus
      influenzae serotype b (Hib) vaccine failure and to determine their risk of other
      serious infections. The families of 323 children with invasive Hib disease after
      appropriate vaccination (i.e. vaccine failure) were contacted to complete a
      questionnaire relating to their health and 260 (80.5%) completed the
      questionnaire. Of the 124 children with meningitis, 18.5% reported serious long
      term sequelae and a further 12.1% of parents attributed other problems to Hib
      meningitis. Overall, 14% (32/231 cases) of otherwise healthy children and 59%
      (17/29 cases) of children with an underlying condition developed at least one
      other serious infection requiring hospital admission. In a Poisson regression
      model, the risk of another serious infection was independently associated with
      the presence of an underlying medical condition (incidence risk ratio (IRR) 7.6,
      95% CI 4.8-12.1; p<0.0001), both parents having had a serious infection (IRR 4.1,
      95% CI 1.6-10.3; p=0.003), requirement of more than two antibiotic courses per
      year (IRR 2.3, 95% CI 1.4-3.6; p=0.001) and the presence of a long-term
      complication after Hib infection (IRR 1.8, 95% CI 1.1-3.1; p=0.03). Thus, rates
      of long-term sequelae in children with vaccine failure who developed Hib
      meningitis are similar to those in unvaccinated children in the pre-vaccine era.
      One in seven otherwise healthy children (14%) with Hib vaccine failure will go on
      to suffer another serious infection requiring hospital admission in childhood,
      which is higher than would be expected for the UK paediatric population.

PMID- 20056190
TI  - Pertussis immunization in paediatric healthcare workers: knowledge, attitudes,
      beliefs, and behaviour.
AB  - Healthcare workers' (HCWs) knowledge, attitudes, and beliefs regarding pertussis
      immunization were assessed and compared to the rate of vaccine uptake. A
      questionnaire was distributed to employees at a paediatric and maternity tertiary
      care centre. Respondents were then offered a dose of the tetanus, diphtheria, and
      acellular pertussis vaccine (Tdap) at a free vaccine clinic. In total, 529 out of
      3051 (17%) employees completed the survey and 61 received the Tdap vaccine.
      Although 76% of participants were willing to be immunized, only 15% presented to
      the clinic. There is a widespread acceptance of pertussis immunization among
      paediatric HCWs. Stated intentions may be poorly predictive of behaviour.
      Education and institutional or public funding may improve vaccine uptake.

PMID- 20056191
TI  - Quantitative analysis of influenza virus-specific B cell memory generated by
      different routes of inactivated virus vaccination.
AB  - We consider both Ab-secreting cell (ASC) and memory B cell (B(Mem)) populations
      in a quantitative analysis of virus-specific B cell memory generated by
      intramuscular or intranasal vaccination of mice with inactivated influenza virus.
      After both forms of vaccination, the memory phase was characterized by
      localization of ASCs in the bone marrow and dispersion of B(Mem) to organized
      lymphoid tissues. The stronger IgG response to intramuscular vaccination
      correlated with larger numbers of IgG ASCs in the bone marrow and IgG B(Mem). IgA
      production was only prominent in the response to intranasal vaccination and was
      associated with IgA ASC localization in the lung and IgA B(Mem) formation.
      Notably, few IgG ASCs or B(Mem) localized in the lung after intramuscular
      vaccination, in contrast to the situation following influenza pneumonia. Our
      analysis links the nature of immunization to characteristics of the state of B
      cell memory that may relate to protective immunity.

PMID- 20056192
TI  - Indirect effect of conjugate pneumococcal vaccination in a 2+1 dose schedule.
AB  - In 2006, the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in
      the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule;
      immunisations are administered at 3, 5 and 12 months. Changes in invasive
      pneumococcal disease in all ages from the baseline years 2004-2005 to 2008 were
      assessed, focusing on the indirect effect in the unvaccinated population.
      Following the introduction of PCV7, incidence rates of IPD caused by vaccine
      serotypes declined across all age groups, the decline being statistically
      significant for the age groups <5 years, 5-19 years, 40-64 years and > or = 65
      years. In the unvaccinated population aged > or = 5 years the incidence rate of
      IPD caused by PCV7 serotypes declined by 48% from 12.34 cases/100,000 population
      to 6.44 cases/100,000 population, accounting for 74% of prevented cases of IPD in
      2008. Among the adults aged > or = 65 years the incidence rate of IPD caused by
      serotypes not included in PCV7 increased. No vaccine failure was identified,
      indicating a very high effectiveness of the 2+1 dose schedule vaccination
      programme.

PMID- 20056193
TI  - Two-dimensional patterns of human enamel thickness on deciduous (dm1, dm2) and
      permanent first (M1) mandibular molars.
AB  - OBJECTIVE: To characterise patterns of enamel thickness on deciduous (dm1, dm2)
      and permanent first (M1) mandibular molars and evaluate these against functional
      and morphological interpretative models. METHODS: Histological sections of mesial
      and distal cusps from 69 unworn molars were produced and examined using
      transmitted light microscopy. Enamel cap area, dentine area, as well as average
      and linear measurements of enamel thickness were recorded from digital images of
      the sections using image analysis software. Comparisons were made along the molar
      row, and between the mesial and distal sections of each tooth, using univariate
      and multivariate inferential statistics. RESULTS: The enamel cap area, dentine
      area, and average enamel thickness increased from the anterior to the posterior
      molars. The greatest proportional increase in linear enamel thickness occurred
      between the outside surface of the lingual cusps when dm1 was compared to dm2,
      and between the outside surface of the buccal cusps when dm2 was compared to M1.
      The enamel cap area increased from the mesial to the distal sections in M1.
      Dentine area decreased from the mesial to distal sections in dm1. Enamel cap and
      dentine areas did not change across dm2. CONCLUSION: Results for the deciduous
      molars are interpreted within a functional model of mastication, in which the dm2
      dissipates less laterally orientated loads compared to dm1. Differences in enamel
      thickness between dm2 and M1 support previous functional interpretations for this
      permanent molar. Some mesial-distal results are not easily explained from either
      a functional or a morphological perspective and suggest an underlying
      developmental constraint.

PMID- 20056194
TI  - Fibronectin supports TNF-alpha-induced osteopontin expression through beta1
      integrin and ERK in HN-22 cells.
AB  - The extracellular matrix (ECM), in collaboration with intracellular signal, plays
      a critical role in the modulation of cellular behavior and function. Herein, we
      investigated the influence of fibronectin (FN) and tumor necrosis factor-alpha
      (TNF-alpha) on OPN expression in HN-22, a human head and neck squamous cell
      carcinoma (HNSCC) cell line. The data showed that TNF-alpha significantly
      increased OPN expression only in the FN-coated condition. Application of function
      blocking antibody directed against beta1 integrin abolished this OPN induction.
      Moreover, TNF-alpha when added together with activating beta1 integrin antibody
      is sufficient to induced OPN expression. The combination effect of FN and TNF
      alpha was significantly deteriorated by a MEK inhibitor, but not NF-kappaB
      inhibitor. We further demonstrated that the phosphorylation of ERK1/2 was
      strongly enhanced by TNF-alpha and FN compared to the application of either one
      alone. Synergistic effect on ERK1/2 phosphorylation was also detected by TNF
      alpha and activating beta1 integrin antibody, whereas inhibitory antibody to
      beta1 integrin attenuated FN and TNF-alpha-induced phosphorylation of ERK1/2. Our
      results indicate that FN coordinates TNF-alpha-mediated OPN induction via beta1
      integrin-dependent signaling mechanism that activates ERK. The results suggest
      the critical role of tumor micro-environment signaling networks on the regulation
      of cytokine expression profiles during tumor progression.

PMID- 20056195
TI  - When do trauma experts choose exposure therapy for PTSD patients? A controlled
      study of therapist and patient factors.
AB  - To investigate when and why therapists opt for or rule out imaginal exposure (IE)
      for patients with posttraumatic stress disorder (PTSD), 255 trauma experts were
      randomized to two conditions in which they were presented with four cases in
      which the patients' comorbidity and treatment preferences were manipulated. The
      results confirmed IE to be an underutilized approach, with the majority of
      professionals being undertrained in the technique. As predicted, the patient
      factors influenced the expert's choice of therapy: in case of a comorbid
      depression, IE was significantly less preferred than medication. Also, IE was
      significantly more likely to be offered when patients expressed a preference for
      trauma-focused treatment. The therapist factors were also found to be importantly
      related to treatment preferences, with high credibility in the technique being
      positively related to the therapists' preference for IE. Perceived barriers to
      IE, such as a fear of symptom exacerbation and dropout, were negatively related
      to the perceived suitability of the treatment when patients had suffered multiple
      traumas in childhood. The results are discussed in the light of clinical
      implications and the need of exposure training for trauma professionals.

PMID- 20056196
TI  - Fusion of HBsAg and prime/boosting augment Th1 and CTL responses to HCV polytope
      DNA vaccine.
AB  - Correlation of hepatitis C virus (HCV) spontaneous resolution with Th1 and
      CD8(+)CTL responses during natural infection implies the potentiality of poly-CTL
      epitopic HCV vaccines. We recently reported in silico design and construction of
      DNA vaccines (pcPOL-plasmids) harboring HCV CTL epitopes. Herein, we provide data
      of mice immunization by pcPOL, (encoding; core(132-142) [C], E2(405-414) [E(4)],
      E2(614-622) [E(6)] and NS3(1406-1415) [N] CD8(+)CTL epitopes as CE(4)E(6)N
      polytope) and its HBsAg-fused counterpart (pcHPOL), compared to the adjuvant
      formulated (Montanide+CpG) CE(4)E(6)N synthetic-peptide immunization. All
      vaccinated groups developed different levels of cellular responses, however, only
      the pcHPOL-immunized mice elicited strong CTLs and IFN-gamma-secreting cells that
      were further augmented towards a Th1 response and partial tumor protection by DNA
      prime/peptide-boosting regimen. Priming with HBsAg alone could not afford its
      augmenting effect indicating the importance of priming by polytope itself. Hence,
      fusion of immunocarriers like HBsAg conjoined with DNA-prime/peptide-boost
      immunization regimen seems a strategy to enhance the epitope-specific immune
      responses towards poly-CTL-epitopic vaccines.

PMID- 20056197
TI  - Experimental validation of a radiographic simulation code using breast phantom
      for X-ray imaging.
AB  - Computer models and simulations of X-ray imaging systems are becoming a very
      precious tool during the development and evaluation of new X-ray imaging
      techniques. To provide, however, a faithful simulation of a system, all
      components must be accurately modelled and tested, followed by verification
      through experimental measurements. This paper presents a validation study of the
      XRayImagingSimulator, an in-house developed X-ray imaging simulator, which is
      extensively used as a basic tool in carrying out complex breast imaging
      simulations. The approach followed compares results obtained via an experimental
      setup for breast phantom (CIRS 011A) imaging, using synchrotron radiation (SYRMEP
      beamline at ELETTRA), with those from its simulated setup under the same
      conditions. The study demonstrated a very good agreement between experimental and
      simulated images compared both in terms of subjective and objective criteria. The
      combination of the XRayImagingSimulator with our BreastSimulator provides a
      powerful tool for in silico testing of new X-ray breast imaging approaches.

PMID- 20056198
TI  - Uterine electromyogram database and processing function interface: An open
      standard analysis platform for electrohysterogram signals.
AB  - The uterine electromyogram or electrohysterogram (EHG) is one of the most
      promising biophysical markers of preterm labor. At this time no recording
      parameter standard exists for EHG recordings which can be a problem for the
      establishment of international multicentric trials. In this paper, we present a
      management and processing system dedicated to storing and processing EHG signals.
      This system can process EHG signals recorded in different experimental conditions
      i.e. different sampling frequencies. The signal management is performed using an
      easy to use graphical user interface. Other available functions include
      visualization, preprocessing and analysis of EHG signals. The proposed processing
      functions provide temporal, spectral and time-scale parameters obtained from the
      EHG bibliography. The obtained results from real signals recorded in two
      different hospitals in two different countries are in accordance with the
      literature and demonstrate the potential of the proposed system. The
      incorporation of new functions is easy, due to a standardization of the EHG data
      formats.

PMID- 20056199
TI  - The role of alendronate in mitigating perimenopausal bone loss: a double-blind
      randomized controlled pilot study.
AB  - Compared with placebo, alendronate treatment resulted in a significant protection
      against bone loss in healthy perimenopausal women. This protection occurred at
      both the spine and the hip and was evident after 6 months of therapy.

PMID- 20056200
TI  - Mechanisms regulating invasiveness and growth of endometriosis lesions in rat
      experimental model and in humans.
AB  - OBJECTIVE: To compare the expression of MMP-2, TIMP-2, and TGFbeta2 mRNA in
      experimental and human endometriotic lesions and to assess the possibility of its
      cytokine regulation. DESIGN: Experimental laboratory study. SETTING: Medical
      center. ANIMALS AND PATIENT(S): Thirty female Wistar rats, 17 women with
      endometriosis, 11 healthy women. INTERVENTION(S): Uterine transplants were
      attached to rat peritoneum via the surgical autotransplantation technique. The
      collection of endometriotic implants at 7, 14, and 21 days postsurgery and
      laparoscopic collection of peritoneal fluid, ectopic, and matched eutopic
      endometrium from women with endometriosis were performed. MAIN OUTCOME
      MEASURE(S): MMP-2, TIMP-2, TGFbeta2 mRNA expression in endometrium was assessed
      by real-time reverse-transcription polymerase chain reaction. RESULT(S): In rats,
      the increase of MMP-2 and decrease of TIMP-2 mRNA expression was noted at the 7th
      day, and an increase of TGFbeta2 mRNA expression was seen at the 14th day
      postsurgery. In humans, elevation of TIMP-2 mRNA expression in eutopic
      endometrium and of MMP-2, TGFbeta2 mRNA expression in ectopic endometrium was
      observed. Autologous peritoneal fluid stimulated MMP-2 mRNA expression in eutopic
      endometrium of women with endometriosis. Cytokines derived from ectopic lesions
      mononuclear cells increased TGFbeta2 mRNA expression in endometrium of healthy
      women. CONCLUSION(S): Supposedly MMP-TIMP balance is important in promoting
      endometriotic tissue invasion and TGFbeta2 in regulating ectopic endometrium
      growth.

PMID- 20056201
TI  - Acquisition and loss of oocyte meiotic and developmental competence during in
      vitro antral follicle growth in mouse.
AB  - OBJECTIVE: To analyze the effect of various culture periods and FSH on oocyte
      competence in cultured mouse follicles. DESIGN: Controlled in vitro laboratory
      experiment. SETTING: Academic research environment. INTERVENTION(S): DNA
      staining, maturation induction, parthenogenesis, and IVF were performed after
      various periods of oocyte culture. Additionally, FSH modulation during preantral
      follicle growth was studied. MAIN OUTCOME MEASURE(S): Nucleolar conformation,
      meiotic resumption, activation potential, and preimplantation development were
      recorded. RESULT(S): Surrounded nucleolus (SN) conformation was found in oocytes
      cultured for 8 days and correlated by time with meiotic competence. Culture for
      12 days increased oocyte diameter (day 8 69.8 mum vs. day 12 72.4 mum) and
      meiotic competence (day 8 63% vs. day 12 81% polar body oocytes), but decreased
      fertilization rate (day 8 75% vs. day 12 53% 2-cell embryos). Equal activation
      potential (49%) on both days indicated that impaired sperm entry could not
      account for lower fertilization rate after 12 days. Depriving early follicular
      growth of FSH delayed antrum formation but not SN conformation. CONCLUSION(S):
      Fertilization of cultured oocytes is most efficient close to the completion of
      SN. Omitting FSH from early follicle growth could not postpone the early onset of
      SN, which seems to be imposed by the time spent in vitro.

PMID- 20056202
TI  - Transcervical retrieval of fetal cells in the practice of modern medicine: a
      review of the current literature and future direction.
AB  - OBJECTIVE: To review published methods for transcervical collection of fetal
      cells and to assess the potential of this approach for application in prenatal
      diagnosis. MAIN OUTCOME MEASURE(S): Retrospective analysis of efforts at prenatal
      diagnosis with trophoblast cells shed into the lower uterine pole that accumulate
      within the cervical mucus at the level of the internal os. RESULT(S): Minimally
      invasive techniques that include cervical mucus aspiration, cervical swabbing,
      and cervical or intrauterine lavage can be used to retrieve trophoblast cells
      during the first trimester for diagnostic purposes, including for prenatal
      genetic analysis. Fetal cells have been identified in these specimens with
      success rates that vary from 40% to 90%. The disparity in reported success rates
      can be a function of gestational age, collection method, operator variability,
      detection sensitivity, or pregnancy status. Molecular approaches have been
      devised to determine fetal sex and identify aneuploidies. Antibody markers have
      proven useful to select trophoblast cells for genetic analysis and to demonstrate
      that the abundance of recoverable fetal cells diminishes in abnormal gestations,
      such as in ectopic pregnancy or blighted ovum. CONCLUSION(S): Transcervical
      collection of fetal cells offers several avenues for prenatal diagnosis that with
      further refinement could one day provide valuable information for the management
      of ongoing pregnancies.

PMID- 20056203
TI  - Two cases of myomectomy complicated by intravascular hemolysis and renal failure:
      disseminated intravascular coagulation or hemolytic uremic syndrome?
AB  - OBJECTIVE: To present two cases of myomectomy complicated by intravascular
      hemolysis leading to acute renal failure and discuss the differential diagnosis
      and possible mechanism. DESIGN: Case report. SETTING: Minimally Invasive Therapy
      Unit, University Department of Obstetrics and Gynecology. PATIENT(S): Two
      premenopausal patients with uterine fibroids. INTERVENTION(S): Both patients
      underwent otherwise uncomplicated myomectomies, one by laparotomy and one by
      laparoscopy, with tourniquets around the uterine and ovarian vessels being used
      to control intraoperative bleeding. MAIN OUTCOME MEASURE(S): Renal function in
      the postoperative period. RESULT(S): Both patients developed a very rare
      complication after surgery of severe thrombocytopenia with microangiopathic
      hemolytic anemia leading to acute renal failure. One patient made a full recovery
      within weeks but the other still has reduced renal function almost 2 years after
      the surgery. The differential diagnosis consisted of disseminated intravascular
      coagulation or hemolytic uremic syndrome. CONCLUSION(S): The etiology of
      thrombotic microangiopathy in these patients was unclear, but disruption and
      manipulation of fibroids during surgery may have led to the dissemination of pro
      coagulant tissue factor containing particles leading to disseminated
      intravascular coagulation or hemolytic uremic syndrome, perhaps aggravated by
      utero-ovarian ischemia caused by the tourniquets.

PMID- 20056204
TI  - Asian ethnicity in anonymous oocyte donors is associated with increased estradiol
      levels but comparable recipient pregnancy rates compared with Caucasians.
AB  - OBJECTIVE: To determine if differences exist in ovarian response and pregnancy
      rates between Asian and Caucasian donors. DESIGN: Retrospective cohort study.
      SETTING: University-based clinic. PATIENT(S): Anonymous oocyte donors of self
      reported Asian (n=63) or Caucasian (n=156) ethnicity who began ovarian
      stimulation between February 2000 and March 2008 and their matched recipients.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Recipient pregnancy rates and
      oocyte donor ovarian responsiveness. RESULT(S): Baseline characteristics were
      similar between Asian and Caucasian donors. Asian donors had peak serum estradiol
      levels that were 23% higher than their Caucasian counterparts (3715+/-220 vs.
      3013+/-114 pg/mL). Adjusted estradiol levels per follicle measured and per oocyte
      retrieved were elevated in Asian donors (17% and 23% higher, respectively), and
      these differences were unchanged after adjusting for body mass index. No
      differences were noted in implantation rates (47.4% vs. 40.9%), clinical
      pregnancy rates (60.3% vs. 62.4%), or live-birth rates (55.5% vs. 59.9%) achieved
      using Asian vs. Caucasian oocyte donors. CONCLUSION(S): In contrast to autologous
      fresh in vitro fertilization cycles, Asian ethnicity is not associated with a
      lower pregnancy rate in recipient women using controlled hormone replacement when
      anonymous donor oocytes are used. Asian donors achieved statistically
      significantly higher serum estradiol levels during gonadotropin stimulation,
      suggesting an ethnic difference in steroid production and/or metabolism.

PMID- 20056205
TI  - Fate of cryopreserved donor embryos.
AB  - OBJECTIVE: To review a center's experience with cryopreserved embryos generated
      from donor eggs and to analyze their long-term disposition. DESIGN: Retrospective
      analysis of donor egg cycles with cryopreserved embryos. SETTING: University
      based IVF program. PATIENT(S): Eight hundred twenty-nine women undergoing oocyte
      donation. INTERVENTION(S): N/A. MAIN OUTCOME MEASURE(S): Factors affecting the
      decision regarding disposition of donor frozen embryo transfer (dFET) and the
      association between fresh and dFET cycles. RESULT(S): From January 2000 to
      December 2004, donor egg recipients underwent 829 fresh embryo transfer cycles
      that resulted in a 54% live birth rate. Of the 444 recipients who delivered, 177
      (40%) also cryopreserved embryos at transfer; however, only 37 (21%) returned for
      a dFET by August 2009 and only 18 women had children from fresh and frozen
      transfers. In contrast, 128 of the 385 recipients who failed the fresh transfer
      (33%) cryopreserved embryos and 111 (87%) returned for a dFET. Of these, 44 had
      children from the dFET. Frozen cycle success rates between these recipient groups
      did not depend on fresh cycle outcome or prior parity. CONCLUSION(S): Donor
      oocyte recipients often initiate treatment with a desire to cryopreserve embryos
      for future use and family expansion. However, our data demonstrates that most
      recipients with a child from the fresh transfer do not return to use their
      cryopreserved embryos. Although fresh transfer success correlated with embryo
      disposition, it did not correlate with the outcome of thawed embryo transfer.

PMID- 20056206
TI  - Male infertility associated with hereditary leiomyomatosis and renal cell
      carcinoma.
AB  - OBJECTIVE: To report a novel association between a cancer predisposition syndrome
      (hereditary leiomyomatosis and renal cell carcinoma [HLRCC]) and male
      infertility. DESIGN: Case report. SETTING: University medical center adult
      genetics clinic. PATIENT(S): A 31-year-old male of Chinese ancestry referred for
      evaluation of immotile sperm. INTERVENTION(S): Physical examination, family
      history assessment, genetic testing, and cancer screening. MAIN OUTCOME
      MEASURE(S): Genetic testing results. RESULT(S): Physical exam: cutaneous
      leiomyomata on the upper back and left arm. Family history: the patient has a
      sister with uterine leiomyomata. Genetic testing revealed a mutation in the
      fumarate hydratase gene, which codes for an enzyme (fumarase) that has previously
      been implicated in sperm number and motility. More recently, heterozygous
      mutations in this gene have been associated with HLRCC. However, male infertility
      is not a recognized manifestation of this condition. CONCLUSION(S): A
      comprehensive medical (including family) history and physical examination are
      important when evaluating male infertility. Genetics consultation enabled our
      patient and his family to begin appropriate cancer screening and provided
      reproductive options, including prenatal/preimplantation diagnosis. Further
      studies of the relationship between fumarase, HLRCC, and male infertility are
      needed to provide accurate counseling to families and to better understand
      genotype-phenotype correlations.

PMID- 20056207
TI  - The functional genotype of glutathione S-transferase T1 gene is strongly
      associated with increased risk of idiopathic infertility in Russian men.
AB  - This study was designed to investigate the association between null polymorphisms
      of glutathione S-transferase (GST) M1 and T1 genes and idiopathic male
      infertility in a Russian population including 203 infertile and 227 fertile men.
      The nondeletion genotype of the GSTT1 gene was found to be strongly associated
      with the increased risk of idiopathic male infertility and asthenozoospermia.

PMID- 20056208
TI  - Cross-border reproductive care: quality and safety challenges for the regulator.
AB  - Cross-border reproductive care (CBRC) is increasing and poses legal, ethical, and
      moral challenges, not least for the organizations that regulate IVF. Fertility
      treatment in the U.K. is regulated by the Human Fertilisation and Embryology
      Authority which has focused on providing comprehensive information for people
      seeking CBRC, the standards of quality and safety they should expect, and issues
      of donor anonymity, surrogacy, multiple births, and PGD.

PMID- 20056209
TI  - Basal FSH level changes after different types of uterine vessel occlusion in the
      management of uterine fibroids.
AB  - OBJECTIVE: To assess the effect on FSH of the application of different types of
      uterine vessel blockage (uterine artery occlusion alone [UAO] or with blockage of
      vessel anastomosis [UVO]) in the management of women with fibroids. DESIGN: Case
      control study. SETTING: Medical center. PATIENT(S): One hundred ten women with
      uterine fibroids. INTERVENTION(S): Forty-four consecutive patients undergoing UAO
      were compared with 66 matched subjects who underwent UVO during the same period.
      MAIN OUTCOME MEASURE(S): Surgery types and FSH levels were compared. RESULT(S):
      At the first month after surgery, FSH levels were elevated from 5.5 mIU/mL to
      14.2 and 8.7 mIU/mL in the UVO and UAO groups, respectively. The difference
      between the 2 groups continued up to 6 months and disappeared thereafter. More
      patients (38%) in the UVO group had an increased FSH level of >10 mIU/mL,
      compared with 5% in the UAO group at the first month after surgery, which
      contributed to the high percentage of women with irregular menstruation.
      CONCLUSION(S): Women treated with UVO were associated with a greater risk of a
      significant increase in FSH level at the first month after operation than those
      treated with UAO, which may be a reflection of diminished ovarian function. The
      long-term effect was uncertain, because of the lack of difference in the FSH
      levels between the two groups.

PMID- 20056210
TI  - Oxytocin-induced cell growth proliferation in human myometrial cells and
      leiomyomas.
AB  - OBJECTIVE: To assess the expression of the oxytocin receptor (OTR) and the role
      of oxytocin (OT) in the proliferation of myometrial and leiomyoma cells. DESIGN:
      Prospective laboratory study. SETTING: Research laboratory at the Italian
      National Research Council. PATIENT(S): Twenty-two women who underwent therapeutic
      myomectomy for fibroids. INTERVENTION(S): Primary cultures of leiomyoma and
      myometrium cells were established from eutopic and ectopic myometrial tissues. An
      immortalized myometrial cell line (h-TERTmyo) and a leiomyosarcoma cell line (SK
      UT-1) were also characterized. MAIN OUTCOME MEASURE(S): Expression of OTR and
      desmin mRNA was determined by quantitative real-time polymerase chain reaction.
      Cell growth was determined by 3-[4,5-dimethylthiazol-2-yl]5-(3
      carboxymethoxyphenyl)2-(4-sulfophenyl)-2H tetrazolium assay. Apoptosis was
      determined by annexin V cell staining and flow cytometry analysis. RESULT(S):
      Oxytocin stimulated proliferation of primary myometrial and leiomyoma cells but
      inhibited the proliferation of h-TERTmyo and SK-UT-1, indicating a change in
      phenotype during immortalization. A progressive and rapid decrease in desmin and
      OTR mRNA was observed in primary cultures, indicating that myometrial cells
      dedifferentiate very rapidly in culture. The relative expression of OTR mRNA
      varied widely in both myometrial and leiomyoma smooth muscle cells, but there was
      no significant difference. CONCLUSION(S): These results indicate that OT
      stimulates the proliferation of both myometrial and leiomyoma cells,
      demonstrating that the OT/OTR system plays an important role in regulating
      uterine cell growth and providing a rationale for evaluating the use of OTR
      antagonists in managing uterine myomas.

PMID- 20056211
TI  - Mutational analysis of androgen receptor gene in four Chinese patients with male
      pseudohermaphroditism.
AB  - OBJECTIVE: To show mutational analysis for androgen insensitivity syndrome (AIS)
      associated male pseudohermaphroditism (MPH). DESIGN: Case report. SETTING: Key
      laboratory of endocrinology at a university hospital. PATIENT(S): Four unrelated
      Chinese patients with MPH referred to our clinic were investigated in this study.
      INTERVENTION(S): Genomic DNA was extracted from peripheral blood leukocytes, and
      coding sequence abnormalities of androgen receptor (AR) gene were assessed by
      polymerase chain reaction and direct sequencing analysis. MAIN OUTCOME
      MEASURE(S): Molecular characterization of the AR gene. RESULT(S): Four mutations
      (p.P913R, p.D732 N, p.N848 K, fs879X, and p.R608 K) in the AR gene were
      identified in our study. The p.P913R mutation in the AR gene has not been
      described previously. CONCLUSION(S): Our study identified a novel mutation in the
      AR gene that may provide us new insights into the molecular mechanisms of AIS.
      The expanded database of these mutations should benefit patients in the diagnosis
      and treatment of this syndrome.

PMID- 20056212
TI  - Molecular cytogenetic analysis by genomic hybridization to determine the cause of
      recurrent miscarriage.
AB  - OBJECTIVE: To characterize a t(2;6) by array-based comparative genomic
      hybridization (array-CGH) in a couple with recurrent miscarriage, to analyze the
      meiotic segregation of the t(2;6), and to discuss couple specific care-taking
      modality before intracytoplasmic sperm injection. DESIGN: Case report. SETTING:
      INSERM U613 in Brest, France. PATIENT(S): Couple consulting for infertility.
      INTERVENTION(S): Array-CGH to characterize a t(2;6) and fluorescence in situ
      hybridization (FISH) to analyze the meiotic segregation were performed. MAIN
      OUTCOME MEASURE(S): Array-CGH, FISH with a panel of bacterial artificial
      chromosome clones and commercial probes. RESULT(S): Analyses from peripheral
      blood lymphocytes identified a t(2;6)(q35;q24) unbalanced reciprocal
      translocation with microdeletions on the der(2) and the der(6). FISH on
      spermatozoa found that the frequency of normal (23,X or 23,Y) or "translocation
      deletions" (23,X,der(2),der(6) or 23,Y,der(2),der(6)) spermatozoa was 41.10%.
      CONCLUSION(S): For our 46,XY,t(2;6)(q35;q24) carrier, more than 50% of the
      spermatozoa are chromosomally unbalanced. Moreover, FISH does not permit a
      distinction between normal and "translocation-deletion" phenotypes. So, in the
      possibility of preimplantation genetic diagnosis, is it necessary to select the
      normal embryos to the detriment of those translocation-deletions carriers? The
      pathogenicity of these microdeletions not been proved. Because the family history
      was oriented toward a variation of genetic equipment without phenotypic
      consequences, the couple decided not to make a selection between the normal
      embryos and the translocation-deletion carrier embryos.

PMID- 20056213
TI  - Clinical and prognostic significance of human papillomavirus DNA in the sperm or
      exfoliated cells of infertile patients and subjects with risk factors.
AB  - OBJECTIVE: To evaluate human papillomavirus (HPV) sperm infection and its
      correlation with sperm parameters in infertile patients and subjects with risk
      factors. DESIGN: Cross-sectional clinical study. SETTING: Andrology and
      microbiology sections at a university hospital. PATIENT(S): A cohort of 290
      subjects: 26 with genital warts, 66 with HPV positive partners, 108 infertile
      patients, and 90 fertile controls. INTERVENTION(S): Semen analysis, sperm
      culture, polymerase chain reaction, and fluorescence in situ hybridization (FISH)
      for HPV detection. Statistical analysis was performed with a two-tailed Student's
      t-test. RESULT(S): The prevalence of HPV semen infection found in all groups was
      as follows: patients with genital warts, 53.8%; infected partners, 40.9%;
      infertile patients, 10.2%, fertile controls, 2.2%. Infertile patients had a
      higher HPV DNA prevalence in sperm cells than the other groups. The results of
      HPV investigation were compared with sperm parameters and the results of FISH
      analysis. Sperm motility was more frequently reduced in infected samples and in
      particular when the infection was present in the sperm. CONCLUSION(S): This study
      demonstrated a very high prevalence of infection in the semen of patients with
      risk factors for HPV. In each group of subjects, HPV seems to be preferentially
      located in sperm or exfoliated cells, with different effects on sperm motility.

PMID- 20056214
TI  - The role of patients' organizations in cross-border reproductive care.
AB  - This article provides an overview of cross-border reproductive care from a
      patient perspective. It outlines motives for seeking reproductive care outside
      patients' home countries or in other jurisdictions of their home country,
      describes the role of patients' organizations in general, and concludes by
      indicating potentials for collaboration between professionals' and patients'
      organizations.

PMID- 20056215
TI  - A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis
      with an antiangiogenic effect in a rat model.
AB  - OBJECTIVE: To analyze the antiangiogenic effects of the selective cyclooxygenase
      2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat
      model of peritoneal endometriosis. DESIGN: Pharmacologic interventions in an
      experimental model of peritoneal endometriosis. SETTING: Research laboratory in
      the Federal University of Rio de Janeiro. ANIMAL(S): Twenty female Sprague-Dawley
      rats with experimentally induced endometriosis. INTERVENTION(S): After
      implantation and establishment of autologous endometrium onto the peritoneum
      abdominal wall, rats were randomized into groups and treated with parecoxib or
      the vehicle by IM injection for 30 days. MAIN OUTCOME MEASURE(S): Vascular
      density, the expression of vascular endothelial growth factor (VEGF) and its
      receptor Flk-1, the distribution of activated macrophages, the expression of COX
      2, and the prostaglandin concentration in the endometriotic lesions treated with
      parecoxib were analyzed. RESULT(S): The treatment significantly decreased the
      implant size, and histologic examination indicated mostly atrophy and regression.
      A reduction in microvessel density and in the number of macrophages, associated
      with decreased expression of VEGF and Flk-1, also were observed. The treatment
      group showed a low concentration of prostaglandin E(2). CONCLUSION(S): These
      results suggest that the use of COX-2 selective inhibitors could be effective to
      suppress the establishment and growth of endometriosis, partially through their
      antiangiogenic activity.

PMID- 20056216
TI  - Measuring outcomes in fertility trials: can we rely on clinical pregnancy rates?
AB  - OBJECTIVE: To assess whether the estimates of treatment effect in randomized
      clinical trials (RCTs) in reproductive medicine differ when either clinical
      pregnancy or live birth is used as the outcome measure. DESIGN: Metaanalysis.
      SETTING: We analyzed RCTs in reproductive medicine found in systematic reviews
      published in the Cochrane Library that reported on both clinical pregnancy and
      live birth. PATIENT(S): Subfertile couples. INTERVENTION(S): For each individual
      RCT, data on clinical pregnancy and live birth were extracted. MAIN OUTCOME
      MEASURE(S): We compared the outcome of each study by calculating a kappa
      statistic (statistically significant treatment effective or not) and by comparing
      the odds ratio by calculating the ratio of the odds ratios (ROR). RESULT(S): We
      found 67 systematic reviews, of which 42 reported on pregnancy and live birth.
      These 42 reviews included 654 RCTs, of which 143 (22%) reported both on pregnancy
      and live birth. The pregnancy loss rates in the treatment and control groups were
      comparable. Of the 143 RCTs, the conclusion based on pregnancy rate and live
      birth rate was comparable (kappa value of 0.81; 95% confidence interval [CI],
      0.68-0.94). The odds ratios estimating treatment effect from pregnancy and live
      birth were also comparable (ROR, 1.01, 95% CI 0.9 to 1.12). CONCLUSION(S): Only a
      minority of randomized clinical trials in reproductive medicine report on live
      birth. Conclusions on the effectiveness of a treatment based on either clinical
      pregnancy or live birth as endpoints are comparable.

PMID- 20056217
TI  - Overweight and seminal quality: a study of 794 patients.
AB  - OBJECTIVES: To evaluate sperm quality, levels of markers of epididymal and
      accessory gland function, and T in semen from men grouped according to their body
      mass index (BMI). DESIGN: Blind prospective study. SETTING: Andrology and
      reproduction laboratory in Cordoba, Argentina (2006-2007). PATIENT(S): Seven
      hundred ninety-four men. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): In semen
      samples, sperm quality (volume, density, motility, morphology, viability,
      hypoosmotic swell test, and nuclear maturity) and levels of neutral alpha
      glucosidase, fructose, citric acid and T. RESULT(S): Multivariate analysis showed
      a negative association between BMI and motility, rapid motility and neutral alpha
      glucosidase levels, and a positive association between BMI and seminal fructose
      levels. No associations were found among BMI and sperm concentration, the other
      parameters evaluated, or seminal T levels. CONCLUSION(S): Results found in our
      study support a deleterious effect of obesity on seminal quality, probably by
      alterations in the function of the epididymis (i.e., in epididymal maturation).

PMID- 20056218
TI  - The selective progesterone receptor modulator CDB4124 inhibits proliferation and
      induces apoptosis in uterine leiomyoma cells.
AB  - OBJECTIVE: To evaluate the effects of selective P receptor (PR) modulator CDB4124
      on cell proliferation and apoptosis in cultured human uterine leiomyoma smooth
      muscle (LSM) cells and control myometrial smooth muscle (MSM) cells in matched
      uteri. DESIGN: Laboratory research. SETTING: Academic medical center. PATIENT(S):
      Premenopausal women (n = 12) undergoing hysterectomy for leiomyoma-related
      symptoms. INTERVENTION(S): Treatment of primary LSM and MSM cells with CDB4124
      (10(-8)-10(-6) M) or vehicle for 24, 48, or 72 hours. MAIN OUTCOME MEASURE(S):
      Western blot for protein expression of proliferating cell nuclear antigen,
      cleaved polyadenosine 5'-diphosphate-ribose polymerase, Bcl-2, and Kruppel-like
      transcription factor 11; 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium
      bromide (MTT) assay to evaluate viable cell numbers; and real-time polymerase
      chain reaction (PCR) to quantify messenger RNA (mRNA) levels. RESULT(S):
      Treatment with CDB4124 significantly decreased levels of the proliferation marker
      proliferating cell nuclear antigen, the number of viable LSM cells, and the
      antiapoptotic protein Bcl-2. On the other hand, treatment with CDB4124 increased
      levels of the apoptosis marker cleaved polyadenosine 5'-diphosphate-ribose
      polymerase and the tumor suppressor Kruppel-like transcription factor 11 in a
      dose- and time-dependent manner in LSM cells. In matched MSM cells, however,
      CDB4124 did not affect cell proliferation or apoptosis. CONCLUSION(S): CDB4124
      selectively inhibits proliferation and induces apoptosis in LSM but not in MSM
      cells.

PMID- 20056219
TI  - Changes of CD4+CD25high regulatory T cells and FOXP3 expression in unexplained
      recurrent spontaneous abortion patients.
AB  - OBJECTIVE: To investigate the proportions of CD4+CD25high T cells and forkhead
      box p3 (FOXP3) expression in peripheral blood and decidua in patients with
      unexplained recurrent spontaneous abortion (URSA). DESIGN: Prospective clinical
      study. SETTING: University hospital. PATIENT(S): 125 URSA patients, 35 normal
      early pregnant women, and 28 normal nonpregnant women. INTERVENTION(S):
      Measurements of CD4+CD25high T cells and FOXP3 expression in peripheral blood and
      decidua. MAIN OUTCOME MEASURE(S): The proportions of CD4+CD25high T cells and
      FOXP3 expression. RESULT(S): In peripheral blood, statistically significantly
      higher proportions of CD4+CD25high T cells and FOXP3 expression were observed in
      normal early pregnant women compared with normal nonpregnant women and URSA
      patients; a statistically significantly lower proportion of CD4+CD25high T cells
      was observed in nonpregnant URSA patients compared with URSA patients who had
      early miscarriages and normal nonpregnant women. In the decidua, statistically
      significantly lower proportions of CD4+CD25high T cells and FOXP3 expression were
      found in URSA patients with early miscarriages compared with normal early
      pregnant women. CONCLUSION(S): The CD4+CD25high T cells may play an important
      role in maintaining a normal pregnancy. The reduction in CD4+CD25high T cells may
      involve in the pathogenesis of URSA, and is correlated with lower FOXP3
      expression.

PMID- 20056220
TI  - Endometriosis: is laparoscopy justified without previous ultrasonogram and
      magnetic resonance imaging (MRI)?

PMID- 20056221
TI  - Effectiveness of acupressure for residents of long-term care facilities with
      insomnia: a randomized controlled trial.
AB  - BACKGROUND: Acupressure on the Shenmen point (indexed as HT7) can improve
      insomnia, but there has been no longitudinal study to evaluate its efficacy for
      residents of long-term care facilities. No evidence from the existing literature
      indicates how long its efficacy can be maintained after stopping acupressure.
      OBJECTIVE: The aim of this study was to evaluate the effectiveness of acupressure
      on the Shenmen point for residents of long-term care facilities with insomnia.
      METHODS: Fifty residents with insomnia in long-term care facilities were enrolled
      in a randomized controlled trial, with 25 participants allocated to the
      experimental group and 25 participants to the control group. For a 5-week period,
      the experimental group received standard acupressure on the HT7 points of both
      wrists, whereas the control group received only light touch on the same places.
      Insomnia was measured with the Athens Insomnia Scale-Taiwan form (AIS-T).
      Participants' self-reported scores were done at baseline, during the 5-week
      period, and after intervention. This study was analyzed on an intention-to-treat
      procedure. RESULTS: The experimental group has significantly better scores on the
      AIS-T compared to the control group, not only during the intervention period, but
      also extending after intervention, as shown by generalized estimating equations
      (p<0.05). CONCLUSIONS: Offering acupressure on a regular basis has the potential
      to improve insomnia in residents of long-term care facilities. Acupressure on the
      HT7 point may improve insomnia for up to 2 weeks after the intervention.

PMID- 20056222
TI  - Evaluation of translocator protein quantification as a tool for characterising
      macrophage burden in human carotid atherosclerosis.
AB  - Macrophage presence within atherosclerotic plaque is a feature of instability and
      a risk factor for plaque rupture and clinical events. Activated macrophages
      express high levels of the translocator protein/peripheral benzodiazepine
      receptor (TSPO/PBR). In this study, we investigated the potential for quantifying
      plaque inflammation by targeting this receptor. TSPO expression and distribution
      in the plaque were quantified using radioligand binding assays and
      autoradiography. We show that cultured human macrophages expressed 20 times more
      TSPO than cultured human vascular smooth muscle cells (VSMCs), the other abundant
      cell type in plaque. The TSPO ligands [3H](R)-1-(2-chlorophenyl)-N-methyl-(1
      methylpropyl)-3-isoquinoline carboxamide ([3H](R)-PK11195) and [3H]N-(2,5
      dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide ([3H]-DAA1106) bound to
      the same sites in human carotid atherosclerotic plaques in vitro, and
      demonstrated significant correlation with macrophage-rich regions. In conclusion,
      our data indicate that radioisotope-labelled DAA1106 has the potential to
      quantify the macrophage content of atherosclerotic plaque.

PMID- 20056223
TI  - Genetic and environmental determinants of total and high-molecular weight
      adiponectin in families with low HDL-cholesterol and early onset coronary heart
      disease.
AB  - OBJECTIVE: Plasma adiponectin and high-density lipoprotein cholesterol (HDL-C)
      exhibit a well-known positive metabolic correlation. Neither heritability nor
      genome-wide linkage analysis for the high-molecular weight (HMW) adiponectin is
      available. This work estimates the genetic and environmental determinants and the
      heritabilities of the adiponectins and lipid traits in Finnish families with
      early onset coronary heart disease (CHD) and low HDL-C. METHODS: Heritability and
      genome-wide univariate linkage analysis was performed for total and HMW
      adiponectin in extended families from Northern Finland with early onset CHD and
      low HDL-C using a variance components approach. The genetic and environmental
      correlations between the plasma adiponectins and various lipid traits were also
      studied and a bivariate analysis for HDL-C and the adiponectins carried out.
      RESULTS: In the partial correlation analysis (adjusted for sex, age, BMI and
      statin use) the adiponectins showed a stronger correlation with HDL-C (total
      0.57, p=0.001, HMW 0.51, p<0.005) than with any other lipid trait in unrelated
      subjects. Our estimates detected strong heritability for total (0.53+/-0.10), HMW
      (0.51+/-0.10) and the HMW/total adiponectin ratio (0.68+/-0.11). Univariate
      linkage analysis showed suggestive evidence of linkage on chromosome 11p15 for
      total adiponectin and on 3q13.2-q24 and 6p21 for the HMW adiponectin. The
      strongest environmental cross-correlation between the adiponectins and lipids was
      seen between HDL-C and total adiponectin (rhoe=0.64, p<0.05), whereas the
      strongest genetic correlation was detected between low-density lipoprotein
      cholesterol and the HMW adiponectin (rhog=-0.48, p<0.05). CONCLUSION: No
      significant genetic correlations between HDL-C and the adiponectins were
      observed. Therefore, the metabolic association between HDL-C and adiponectin is
      most likely regulated by complex genetic pathways and environmental factors.

PMID- 20056224
TI  - Metabolic syndrome is an independent predictor of cardiovascular events in high
      risk patients with occlusive and aneurysmatic peripheral arterial disease.
AB  - OBJECTIVE: Metabolic syndrome (MetSyn) is a well-known risk factor for
      cardiovascular (CV) disease in the general population; however, the additional
      predictive value for CV events in high-risk patients with peripheral arterial
      disease (PAD) is unknown. The aims of the current study were to assess and
      compare: (1) prevalence of MetSyn, and (2) predictive value of MetSyn for CV
      events, in patients with either occlusive or aneurysmatic PAD. METHODS: We
      screened 2069 patients scheduled for lower occlusive arterial revascularization
      (n=1031) or abdominal aortic aneurysm repair (n=1038) for the presence of MetSyn.
      Adult Treatment Panel III report (ATP III) was used for defining MetSyn. Central
      obesity was defined as body-mass-index>30 kg/m2. Main outcomes were the
      occurrence of CV events and CV mortality during a median follow-up of 6 years
      (IQR 2-9 years). RESULTS: Metabolic syndrome was diagnosed in 421 (41%) and 432
      (42%) patients with occlusive and aneurysmatic PAD, respectively (p=0.72).
      Patients with occlusive or aneurysmatic PAD and MetSyn had an increased risk for
      the development of CV events, when compared to patients without MetSyn (27% vs.
      18% and 27% vs. 19%, p<0.001, respectively). In occlusive and aneurysmatic PAD,
      MetSyn was independently associated with an increased risk of CV events (HR=1.6;
      95%CI 1.2-2.1 and HR=1.4; 95%CI 1.1-1.8). No significant association between the
      presence of MetSyn and CV mortality was observed. CONCLUSIONS: Metabolic syndrome
      is highly prevalent in high-risk PAD patients. In occlusive and aneurysmatic PAD
      patients, MetSyn is an independent predictor of long-term CV events.

PMID- 20056225
TI  - Increased serum YKL-40 and C-reactive protein levels are associated with
      angiographic lesion progression in patients with coronary artery disease.
AB  - OBJECTIVE: YKL-40 is a pro-inflammatory protein highly expressed in
      atherosclerotic plaques, and is related to prognosis of patients with coronary
      artery disease (CAD). This study aimed to assess the possible association between
      YKL-40 and coronary lesion progression in CAD patients. METHODS: A total of 313
      patients with CAD, who underwent percutaneous coronary intervention (PCI) and
      follow-up angiography (mean 13.2+/-3.2 months) were recruited. Serum YKL-40 and
      high-sensitivity C-reactive protein (hsCRP) levels were measured using ELISA
      kits. RESULTS: Baseline serum YKL-40 and hsCRP levels were higher in those with
      lesion progression (all p<0.001 vs. patients without lesion progression), and
      correlated significantly with change of lumen diameter stenosis and cumulative
      coronary obstruction score (all p<0.01). Multivariable logistic regression
      analysis revealed that after adjusting for conventional risk factors, number of
      total coronary artery lesions, YKL-40 and hsCRP levels were independent
      determinants of lesion progression. An area under the curve of YKL-40 and hsCRP
      was 0.744 (CI 95% 0.685-0.804, p<0.001) and 0.716 (CI 95% 0.657-0.776, p<0.001),
      respectively. The optimal values of cut-off point were 74.98 ng/ml (sensitivity
      70%, specificity 71%) for YKL-40 and 3.21 mg/l (sensitivity 66%, specificity 68%)
      for hsCRP to predict lesion progression. CONCLUSION: Increased serum YKL-40 and
      hsCRP levels are independently associated with lesion progression in patients
      with CAD.

PMID- 20056226
TI  - Anisotropy and inhomogeneity of the trabecular structure can describe the
      mechanical strength of osteoarthritic cancellous bone.
AB  - Osteoarthritic cancellous bone was studied to investigate the development of this
      pathology, and the functional changes it induces in the bone. In order to predict
      how the morphological alterations of the tissue induced by the pathology can
      change the mechanical properties of the structure, two different strategies have
      been used in the literature: (1) emphasising the influence of structural
      anisotropy; (2) stressing the highly inhomogeneous characteristics of cancellous
      bone. The aim of the present study was to verify the theory that mechanical
      strength of osteoarthritic cancellous bone depends both on tissue anisotropy and
      inhomogeneity. Twenty-five specimens were extracted from osteoarthritic femoral
      heads, along selected directions, and analysed by means of a microtomograph. The
      same specimens were mechanically tested in compression to determine the
      mechanical strength. The most representative structural parameters, confirmed by
      a stepwise analysis, were used to define four models to describe the measured
      mechanical strength. The models were applied neglecting (global analysis) or
      considering (local analysis) tissue inhomogeneities to verify whether the
      correlation with ultimate stress could be improved. The coefficient of
      determination increased from 0.53, considering only bone volume fraction, up to
      0.88, combining it with off-axis angle and normalised eigenvalue. A further
      improvement was found performing a local analysis (R(2)=0.90), which corresponded
      to a decrease of 17% in the residual error. The proposed approach of considering
      both tissue anisotropy and inhomogeneity improved the accuracy in predicting the
      mechanical behaviour of cancellous bone tissue and should be suitable for more
      general loading conditions.

PMID- 20056227
TI  - Fabrication of oriented poly-L-lysine/bacteriorhodopsin-embedded purple membrane
      multilayer structure for enhanced photoelectric response.
AB  - A poly-L-lysine (PLL)/bacteriorhodopsin-embedded purple membrane (bR-PM)
      multilayer film has been successfully constructed by a layer-by-layer (LbL)
      assembly process to enhance the photoelectric response of bR. The assembly
      conditions were investigated and optimized. The PLL/bR-PM adsorption process was
      in situ studied by surface plasmon resonance and the growth of multilayer was
      further characterized by UV-vis absorption spectroscopy. The results indicate
      that the amount of adsorbed bR-PM vs. the assembled layer number exhibits linear
      relationship. The atomic force microscopy images of sequentially assembled PLL/bR
      PM bilayers show that the patch structure of bR-PM in the structure is well
      preserved and the roughness increases with increase of the bilayer number. The
      peak photocurrent generated from PLL/bR-PM film increases with increase of the
      PLL/bR-PM bilayers until achieving a maximum value. The photocurrent of bR-PM
      from the film through PLL assembler is higher than those assembled by other
      polycations, thus rendering a new platform to effectively enhance the bR
      photoelectric responses.

PMID- 20056228
TI  - Characterization of different conformations of bovine serum albumin and their
      propensity to aggregate in the presence of N-cetyl-N,N,N-trimethyl ammonium
      bromide.
AB  - To characterize the structural changes in bovine serum albumin (BSA) on the
      addition of N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB) and to understand the
      mechanism underlying aggregation of resulting protein-surfactant complex, UV
      visible absorbance, steady-state fluorescence, SDS-PAGE gel electrophoresis,
      dynamic light scattering (DLS), and circular dichroism measurements of BSA-CTAB
      solutions were carried out. Changes in UV-visible absorbance and the fluorescence
      intensity on the addition of CTAB indicate the binding of CTAB to BSA. Changes in
      SDS-gel pattern of pepsin digested BSA sample, circular dichroism band at 222 nm,
      ANS intensity of BSA-ANS solution and hydrodynamic diameter of native state
      monomer on the addition of CTAB indicate that BSA unfolds in the presence of
      CTAB. Changes in the heme binding profile, temperature dependence of the heme
      binding profile and change from mixed to dynamic quenching in acrylamide
      quenching experiments of BSA solution on the addition of CTAB indicate that BSA
      unfolds to an intermediate. Turbidity and DLS measurements at 298 K, 323 K and
      358 K indicate that the order of propensity to aggregate for different
      conformations of protein is: denatured > intermediate > native. The formation of
      aggregates is influenced by the nature of head and tail of the surfactant.

PMID- 20056230
TI  - Diagnosis of esophageal atresia with tracheoesophageal fistula: is there a need
      for gastrointestinal contrast?

PMID- 20056231
TI  - Complication after "home treatment" of polydactyly.

PMID- 20056232
TI  - Autism spectrum disorders in extremely preterm children.
AB  - OBJECTIVES: To investigate the prevalence, correlates, and antecedents of autism
      spectrum disorders (ASD) in extremely preterm children. STUDY DESIGN: We
      conducted a prospective study of all births <26 weeks gestation in the United
      Kingdom and Ireland in 1995. Of 307 survivors at 11 years, 219 (71%) were
      assessed and compared with 153 term-born classmates. Parents completed the Social
      Communication Questionnaire (SCQ) to assess autism spectrum symptoms, and ASD
      were diagnosed by using a psychiatric evaluation. An IQ test and clinical
      evaluation were also administered. Longitudinal outcome data were available for
      extremely preterm children. RESULTS: Extremely preterm children had significantly
      higher SCQ scores than classmates (mean difference, 4.6 points; 95% CI, 3.4-5.8).
      Sixteen extremely preterm children (8%) were assigned an ASD diagnosis, compared
      with none of the classmates. By hospital discharge, male sex, lower gestation,
      vaginal breech delivery, abnormal cerebral ultrasound scanning results, and not
      having had breast milk were independently associated with autism spectrum
      symptoms. By 6 years, independent associates were cognitive impairment,
      inattention and peer problems, withdrawn behavior at 2.5 years, and not having
      had breast milk. CONCLUSIONS: Extremely preterm children are at increased risk
      for autism spectrum symptoms and ASD in middle childhood. These symptoms and
      disorders were associated with neurocognitive outcomes, suggesting that ASD may
      result from abnormal brain development in this population.

PMID- 20056233
TI  - An unusual dermatosis in a child.

PMID- 20056234
TI  - Peanut allergy saves a patient with cold-induced hypotension and urticaria.

PMID- 20056235
TI  - Treatment adherence in patients with sickle cell anemia.

PMID- 20056236
TI  - Clinical characteristics and outcomes of neonatal pertussis: a comparative study.
AB  - We describe the features and outcomes of neonatal pertussis and compare these
      with neonates with non-pertussis acute respiratory illness from July 2000 through
      December 2007. Patients with pertussis had a more severe course of disease as
      evidenced by the clinical presentation, length of hospitalization, and oxygen
      requirement. Clinicians should have a high index of suspicion so that appropriate
      supportive care can be initiated promptly.

PMID- 20056237
TI  - Cortical visual function in preterm infants in the first year.
AB  - OBJECTIVE: To assess visual function in low-risk preterm infants at 3, 5, and 12
      months corrected age to determine whether the maturation of visual function in
      the first year is similar to that reported in term-born infants. STUDY DESIGN:
      Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent
      ophthalmological examinations and a battery of tests (fix and follow, visual
      fields, acuity, attention at distance, and fixation shift) designed to assess
      various aspects of visual function at 3, 5, and 12 months corrected age. RESULTS:
      The results were comparable with normative data from term-born infants in all
      tests but fixation shift, suggesting that maturation of most aspects of visual
      function is not significantly affected by preterm birth. In contrast, >25% of
      preterm infants failed the fixation shift test at 3 months, with a higher
      percentage of failing at 5 and 12 months. CONCLUSIONS: There is a specific
      profile of early visual behavior in low-risk preterm infants, with a high
      percentage of infants failing a test that specifically assesses visual attention
      and provides a measure of cortical processing.

PMID- 20056238
TI  - Impact of practice policies on pediatric immunization rates.
AB  - OBJECTIVE: To describe the relationship between practice policies and rates of up
      to-date (UTD). STUDY DESIGN: Analysis of data from the 2004-2006 National
      Immunization Survey (NIS). Practice policies evaluated are immunization provider
      involvement in a vaccine registry, participation in the Vaccines for Children
      (VFC) program, and administration of hepatitis B vaccine at birth. The primary
      outcome is rates of being UTD with the 4:3:1:3:3 vaccination series for children
      age 19 through 35 months. RESULTS: The overall rate of UTD is 80.8%; 53.3% of
      children had providers administer hepatitis B vaccine at birth, which was
      associated with significantly higher rates of UTD (79.9% vs. 83.1%, P < .01).
      Children with multiple vaccine providers had lower rates of UTD versus those with
      only 1 vaccine provider (77.3% vs 82.5%; P < .01). In multivariable analysis,
      participation in VFC (OR 1.59, 95%, CI 1.16-2.2) and administration of hepatitis
      B at birth (OR 1.25, 95% CI 1.05-1.5) increased the odds of UTD. Provider
      participation in a vaccine registry did not significantly impact rates or
      likelihood of UTD. CONCLUSIONS: Immunization provider policy decisions, including
      administration of hepatitis B at birth, participation in VFC, and a focus on
      continuity of care, can improve rates of UTD for children in their practice.

PMID- 20056239
TI  - Pronounced secondary milia precipitated by a superficial traumatic abrasion in a
      4-year-old boy.

PMID- 20056240
TI  - Adrenal insufficiency in newborns with congenital diaphragmatic hernia.
AB  - Newborns with congenital diaphragmatic hernia frequently have catecholamine
      unresponsive systemic hypotension and respiratory failure. We found that adrenal
      insufficiency frequently complicates the clinical course of infants with
      congenital diaphragmatic hernia and was associated with increased severity of
      illness.

PMID- 20056241
TI  - Very long-chain acyl-CoA dehydrogenase deficiency in a patient with normal
      newborn screening by tandem mass spectrometry.
AB  - Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can be detected
      through newborn screening with tandem mass spectrometry. We report a patient who
      died as a result of severe brain injury due to hypoglycemia. Newborn screening
      was normal. Postmortem enzyme analysis and molecular testing confirmed the
      diagnosis of VLCADD.

PMID- 20056242
TI  - Clindamycin-resistant group B Streptococcus and failure of intrapartum
      prophylaxis to prevent early-onset disease.
AB  - Guidelines recommend intrapartum antibiotic prophylaxis (IAP) for parturient
      women who have a screen positive for group B Streptococcus (GBS). Clindamycin
      should be used for IAP only if the maternal GBS isolate is susceptible. We report
      a case of clindamycin-resistant GBS disease in a newborn infant whose mother
      received clindamycin IAP, and we review clindamycin susceptibility testing.

PMID- 20056244
TI  - Hypotensive resuscitation combined with polydatin improve microcirculation and
      survival in a rabbit model of uncontrolled hemorrhagic shock in pregnancy.
AB  - BACKGROUND: Obstetric hemorrhage remains a leading cause of maternal death
      internationally. Polydatin is an effective drug in ameliorating microcirculatory
      insufficiency and increasing survival rate in non-pregnant animal model of
      controlled hemorrhagic shock. In the present study, we investigated the effects
      of hypotensive resuscitation combined with Polydatin administration on
      microcirculation and survival rate in a clinically relevant model of uncontrolled
      hemorrhagic shock in pregnancy. MATERIALS AND METHODS: Twenty anesthetized New
      Zealand white rabbits at mid and late gestation were anesthetized, and an ear
      chamber was prepared to examine microvessels by intravital microscopy. Shock was
      induced by transecting a small artery in mesometrium, followed by blood
      withdrawal via the femoral artery to a mean arterial pressure (MAP) of 40-45 mm
      Hg. Animals were randomly divided into two groups (n=10 per group): 30 min after
      hemorrhage induction, hypotensive resuscitation with Ringer's solution to MAP of
      60 mm Hg, followed by a single volume infusion of 4 mL/Kg of normal saline or
      Polydatin at 60 min after hemorrhage induction (group NS, PD). Finally all the
      animals received hemorrhage control and resuscitated with half of the heparinized
      shed blood and Ringer's solution to MAP of 80 mm Hg. RESULTS: At the end of
      resuscitation, compared with group NS, group PD showed significantly improved
      capillary perfusion as indicated by increased arteriole diameter [0.95+/-0.02 of
      baseline (PD), 0.71+/-0.05 of baseline (NS); P=0.000] and higher functional
      capillary density[95.3% +/- 2.6% (PD), 57.2% +/- 4.1% (NS); P=0.000]. Median
      survival time was significantly longer in group PD than that in group NS [4 d
      (PD), 2 d (NS); P=0.000]. CONCLUSIONS: On the basis of hypotensive resuscitation,
      Polydatin administration improved microcirculation and prolonged survival time in
      pregnant rabbit model of uncontrolled hemorrhagic shock.

PMID- 20056243
TI  - Phospholipid profile in the postmortem hippocampus of patients with schizophrenia
      and bipolar disorder: no changes in docosahexaenoic acid species.
AB  - Previous studies with postmortem brain tissues showed abnormalities not only in n
      3 long-chain polyunsaturated fatty acids (PUFA) but also in phospholipid
      metabolism in the cortex of individuals with schizophrenia and mood disorder. In
      this study we investigated whether there is similar abnormality in n-3 long-chain
      PUFAs and/or in phospholipid profile in the hippocampus of schizophrenia and
      bipolar disorder patients compared to unaffected controls. Using high-performance
      liquid chromatography/electrospray ionization-mass spectrometry (LC/MS), the
      phospholipid contents in the postmortem hippocampus from 35 individuals with
      schizophrenia, 34 individuals with bipolar disorder and 35 controls were
      evaluated. Unlike the previous findings form orbitofrontal cortex, we found no
      significant differences in either n-3 long-chain PUFA or total phosphatidylserine
      (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC). However,
      docosapentaenoic acid (n-6, 22:5n-6)-PS and 22:5n-6-PC were significantly lower
      in individuals with schizophrenia or bipolar disorder than the controls. When
      fatty acid contents were estimated from PS, PE and PC, 22:5n-6 was significantly
      lower in both patient groups compared to the controls. From these results we
      concluded that DHA loss associated with these psychiatric disorders may be
      specific to certain regions of the brain. The selective decrease in 22:5n-6
      without affecting DHA contents suggests altered lipid metabolism, particularly n
      6 PUFA rather than n-3 PUFA, in the hippocampus of individuals with schizophrenia
      or bipolar disorder.

PMID- 20056245
TI  - Protective effect of heme oxygenase-1 to pancreas islet xenograft.
AB  - Our work was to study the protective effect of cobalt protoporphyrin (CoPP) on
      islet xenograft and its mechanism. According to CoPP induction of rat pancreas
      islet cells in different concentration and time, the optimal CoPP dosage to
      induce high expression of HO-1 would be determined by examining expression of HO
      1 mRNA and protein in graft and islet function. Subsequently, islet cells with
      untreated, CoPP-induced, and CoPP-induced with zinc protoporphyrin (ZnPP)-blocked
      were randomly transplanted into murine subrenal capsule, then the survival time
      among these different treated groups was compared by blood glucose level and
      pathologic examination and meanwhile the IFN-gamma, TNF-alpha, IL-10, and IL
      1beta level in serum and their mRNA and protein expression would be examined in
      grafts. CoPP at 50 mmol/L for 36 h incubation induced the highest HO-1 mRNA and
      protein expression in islets. CoPP treated islets under low glucose and high
      glucose stimulation exhibited insulin secretion of 30.52 +/- 2.04 MUIU/mL and
      104.60 +/- 5.10 MUIU/mL, respectively in comparison to control (20.35 +/- 1.79
      MUIU/mL and 62.39 +/- 2.50 MUIU/mL, respectively) (P<0.05). CoPP induction could
      increase higher expression of HO-1 in graft (mRNA: 3.33-fold; protein: 2.85
      fold), but ZnPP-blocked would decrease expression of HO-1 (mRNA: 0.72-fold;
      protein: 0.68-fold). The survival time in induction group (14.63 +/- 1.19 d) was
      significantly longer than untreated group (9.88 +/- 2.17 d) and ZnPP-blocked
      group (9.38 +/- 1.60 d). Serum C-peptide in induction group (60.67 +/- 9.87
      pmol/L) was significantly higher than that in untreated group (35.67 +/- 11.72
      pmol/L) and blockage group (34.67 +/- 12.90 pmol/L) (P<0.05). HbA1C in induction
      group (2.37% +/- 0.21%) was significantly lower than that in untreated group
      (3.00% +/- 0.17%) and blockage group (3.07% +/- 0.15%) (P<0.01). The pathologic
      examination showed that lymphocyte infiltration to the graft in induction group
      was obviously less serious than other two groups. The Il-10 level in the serum in
      induction group (72.97 +/- 9.74 pg/mL) was significantly higher than untreated
      group (30.57 +/- 3.94 pg/mL) and blocked group (45.55 +/- 8.26 pg/mL), and the
      expression of IL-10 mRNA in graft was in the same condition. The higher
      expression of HO-1 induced by CoPP in vitro would significantly improve
      pancreatic function, prolong graft survival time, and reduce lymphocyte
      infiltration to the graft. The CoPP induction could be inhibited by ZnPP and its
      mechanism could be related to immune modulation of IL-10.

PMID- 20056246
TI  - Exogenous nitric oxide donation causes desensitization of arteriolar relaxing
      activity in vivo: an intravital analysis in mice.
AB  - BACKGROUND: The NO/cGMP pathway plays a crucial role in regulation of tissue
      perfusion. However, a NO-induced desensitization of cGMP-mediated relaxation has
      been reported in isolated tissue. To examine whether a similar phenomenon can be
      detected in vivo, we analyzed relaxations of microvessels in response to repeated
      applications of NO. MATERIALS AND METHODS: The investigations were performed by
      means of dynamic intravital fluorescence microscopy in the dorsal skinfold
      chamber of female balb/mice. First, the microvasculature was maximally
      preconstricted by the application of the vasoconstrictor 5-hydroxytryptamine.
      Subsequently, relaxation was induced by applying an NO-donator, the S
      nitrosoglutathione, to the contracted vessels. Following buffer exchange,
      constriction and relaxation were repeated. Drugs were given topically into the
      chamber, directly onto the skin muscle. The response of arterioles to topical
      administration of vasoactive drugs was determined as the change of the diameter,
      and quantified using standard software. RESULTS: The relaxation of arterioles was
      reduced after repetitive application. The short pretreatment with NO-donor
      entailed a reduced relaxation of arterioles in response to following application.
      The absolute change in vessel diameter induced by S-nitrosoglutathione was
      significantly reduced from 21 MUm to 16 MUm after the first and the second
      application, respectively. However, the data also revealed a noticeable reduction
      of the constricting activity of 5-hydroxytryptamine during the second
      application, indicating a possible desensitization of the 5-hydroxytryptamine
      response or a humoral and/or neuronal compensatory mechanisms. CONCLUSIONS: The
      NO-induced cGMP-mediated relaxation of microvessels was quantified, and the
      phenomenon of desensitization visualized in vivo by means of dynamic fluorescence
      microscopy.

PMID- 20056247
TI  - Transmyocardial revascularization: a new approach using stents in swine.

PMID- 20056248
TI  - Metalloproteinase expression is associated with traumatic wound failure.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are crucial in the inflammatory and
      remodeling phases of wound healing. We previously reported the correlation
      between pro-inflammatory cytokines and timing of successful combat-wound closure.
      We now extend our studies to investigate the correlation between wound-remodeling
      MMP expression and wound healing. METHODS: Thirty-eight wounds in 25 patients
      with traumatic extremity combat wounds were prospectively studied. Surgical
      debridement with vacuum-assisted closure (VAC) device application was repeated
      every 48 to 72h until surgical wound closure. Wound effluent and patient serum
      were collected at each wound debridement and analyzed for five matrix
      metalloproteinases using the Luminex multiplex system; Millipore Corp, Billerica,
      MA. The primary outcome was wound healing within 30 d of definitive wound
      closure. Impairment was defined as delayed wound closure (>21 d from injury) or
      wound dehiscence. MMP expression was compared between impaired and normal healing
      wounds. RESULTS: Elevated levels of serum MMP-2 and MMP-7 and reduced levels of
      effluent MMP3 were seen in impaired wounds (n = 9) compared with wounds that
      healed (n = 29; P<0.001). Receiver operating characteristic (ROC) curve analysis
      yielded area-under-the-curve (AUC) of 0.744, 0.783, and 0.805, respectively.
      CONCLUSIONS: Impaired wound healing is characterized by pro-inflammatory MMP-2
      and MMP-7. Serum and effluent concentrations of MMP-2, MMP-3, and MMP-7 can
      effectively predict the outcome of traumatic war wounds and can potentially
      provide decision-supportive, objective evidence for the timing of wound closure.

PMID- 20056249
TI  - Clinico-pathological findings in a patient with progressive cerebellar ataxia,
      autoimmune polyendocrine syndrome, hepatocellular carcinoma and anti-GAD
      autoantibodies.
AB  - OBJECTIVE: To report clinical and pathological findings of a patient with late
      onset insulin-dependent diabetes mellitus (IDDM), progressive cerebellar ataxia
      (PCA) and hepatocellular carcinoma (HCC). PATIENT: A 64-year-old woman, with a
      long lasting IDDM, progressively developed a severe cerebellar syndrome and died
      2 years after the onset of the symptoms for a systemic infection. Autoantibodies
      to antigastric parietal cell and anti-pancreatic islet cell resulted positive.
      Autopsy showed a selective loss of Purkinje cells in the cerebellum, with an
      increase of Bergmann glia and variable microglial proliferation; furthermore, it
      disclosed an HCC. GAD-Abs were detected both in serum and CSF. CONCLUSIONS:
      Clinical and experimental reports suggest a possible role of neoplastic cells in
      producing GAD-Abs. We postulate, in our case, that HCC could have been
      responsible for an overproduction of GAD-Abs, leading to the onset of PCA. Thus,
      GAD-Abs could be considered as a paraneoplastic marker in a subgroup of patients
      with PCA.

PMID- 20056250
TI  - Pittsburgh compound B binding in poststroke dementia.
AB  - We hypothesize that Pittsburgh compound B (PIB) binding is common in poststroke
      dementia (PSD) and that cognitive decline may be faster in PIB positive patients.
      We performed PIB positron emission tomography (PET) among 17 subjects: 10 PSD
      patients, 4 Alzheimer's disease (AD) patients, and 3 healthy controls. We also
      compared the rate of change in mini-mental state examination (MMSE) between PIB
      positive and negative patients. We detected AD-like PIB binding in 4 PSD patients
      (40%), all the AD patients, and 1 healthy control. The global PIB retention
      standardized uptake value (SUV) at 35-45 min for PIB positive stroke patients was
      1.67 (range 1.56-1.82), which was similar to the AD patients (1.65; range 1.46
      1.88) and was lower than PIB negative patients (1.29, range 1.24-1.34). Mean
      annual MMSE decline for the 4 PIB positive patients was 2.9 and that for the 6
      PIB negative patients was 1. This pilot study suggests that PIB PET is feasible
      for the evaluation of PSD and PIB binding may be common in PSD. Whether presence
      of PIB binding is associated with a more rapid cognitive decline in PSD requires
      further study to confirm.

PMID- 20056251
TI  - Effect of long-term valproate monotherapy on bone mineral density in adults with
      epilepsy.
AB  - BACKGROUND: We evaluated the cross-sectional relationship of duration and dosage
      of valproate monotherapy on bone mineral density (BMD) in adult patients with
      epilepsy. METHODS: The BMD at lumbar level (L2-L4) was measured in consecutive
      adult epileptic patients receiving long-term (> or =2 years) valproate
      monotherapy by dual energy X-ray absorptiometry (DXA). Blood samples were
      collected for total serum calcium, phosphorus, magnesium, 25-hydroxyvitamin D(3)
      and parathormone. Osteopenia and osteoporosis were defined according to the World
      Health Organization operational BMD definition. Cross-sectional associations were
      evaluated using Spearman's correlation coefficient. RESULTS: A total of 41
      patients were studied (mean age 32.3+/-8.2 years, 12 men, mean duration of
      valproate monotherapy 10.6+/-7.4 years). Osteopenia was present in 24% of
      subjects, while no case of osteoporosis was documented. Duration and dosage of
      valproate monotherapy did not correlate with BMD. No association was documented
      between duration or dosage of valproate monotherapy and biochemical parameters.
      CONCLUSIONS: Duration of valproate monotherapy does not correlate with decreased
      BMD in adult patients with epilepsy. No case of osteoporosis was identified in
      patients treated with valproate for a mean period of more than ten years. These
      findings indicate that bone metabolism may not be affected by valproate
      monotherapy.

PMID- 20056252
TI  - Vision impairment in tuberculous meningitis: predictors and prognosis.
AB  - BACKGROUND: Vision impairment is a devastating complication of tuberculous
      meningitis. In the present study we evaluated the predictors and prognostic
      significance of vision impairment in tuberculous meningitis. METHODS: In this
      study, 101 adult patients with tuberculous meningitis were evaluated for vision
      status and physical disability and were followed up for 6 months. Contrast
      enhanced magnetic resonance imaging (MRI) was performed at baseline and 6 months.
      RESULT: Out of 101 patients, 74 patients had normal vision and 27 patients had
      low vision or blindness at enrollment. Thirteen patients died during the study
      period. Out of 88 patients who survived at 6 months, 68 patients had good vision,
      11 patients had low vision and 9 patients had blindness. Predictors of vision
      deterioration were papilledema, cranial nerve palsies, raised cerebrospinal fluid
      protein (>1g/L), and presence of optochiasmatic arachnoiditis in MRI. Predictors
      of blindness, at 6 months, were found to be papilledema, vision acuity < or
      =6/18, cranial nerve palsies, tuberculous meningitis stage II or III, raised
      cerebrospinal fluid protein (>1g/L), optochiasmatic arachnoiditis, and
      optochiasmal tuberculoma. At 6 months, 27 patients had death or severe
      disability. Predictors of death or severe disability at 6 months were vision
      acuity < or =6/18, cranial nerve deficits, hemiparesis, clinical stage II or III,
      and presence of infarct in MRI. CONCLUSION: Vision impairment occurred in one
      fourth of patients with tuberculous meningitis. Principal causes of vision loss
      were optochiasmatic arachnoiditis and optochiasmal tuberculoma. Impaired vision
      predicted death or severe disability.

PMID- 20056253
TI  - Wedge-shaped medullary lesions in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a heterogeneous disease with variable clinical
      features and magnetic resonance imaging (MRI) findings. We report four MS cases
      with unusual wedge-shaped lesions in the paramedian ventral medulla oblongata
      demonstrated on MRI. The clinical features and MRI characteristics of the
      medullary lesions suggest an impairment of venous drainage. We propose that the
      formation of these wedge-shaped lesions may be related to the pattern of venous
      drainage in the ventral medulla and raised venous pressure due to chronic
      cerebrospinal venous insufficiency which has recently been described in MS.

PMID- 20056254
TI  - [Dietary fat intake and incidence of cataracts: The SUN Prospective study in the
      cohort of Navarra, Spain].
AB  - BACKGROUND AND OBJECTIVE: To evaluate prospectively the association between
      dietary fat intake and the incidence of cataracts in participants from the SUN
      cohort. PATIENTS AND METHODS: Among 12308 men and women, initially free of
      cataracts and followed-up for up to 6 years, we identified 182 incident cases of
      cataracts. Fatty acids intake was assessed by a validated 136-item
      semiquantitative food frequency questionnaire. Socio-demographic and
      anthropometric characteristics, lifestyle, health-related habits and information
      about medical conditions were also collected. Incident cases of cataract were
      ascertained by self-reports using a biennale questionnaire. RESULTS: Participants
      belonging to the highest category of omega-6 fatty acids intake had a non
      significantly reduced risk of cataracts in the model adjusted for potential
      confounders but not for other fatty acids (adjusted OR: 0.58; 95% CI: 0.33,
      1.03). When all types of fatty acids (saturated, monounsaturated, polyunsaturated
      omega-6 and polyunsaturated omega-3) were included simultaneously in the same
      multivariable model, this inverse association became significant (adjusted OR:
      0.54 95%CI: 0.29, 0.99). There were no significant associations between other
      dietary fats and the risk of cataracts. CONCLUSION: High intake of omega-6 fatty
      acids showed a modest but significant inverse association with the development of
      cataracts.

PMID- 20056255
TI  - [Prevalence of occult chronic kidney disease and associated variables in a
      population of patients with type 2 diabetes].
AB  - BACKGROUND AND OBJECTIVE: To determine the prevalence of occult chronic kidney
      disease (CKD) and the associated clinical variables in patients with type 2
      diabetes mellitus (DM-2). PATIENTS AND METHOD: Observational, laboratory and
      cross-sectional study of patients with DM-2 from primary care settings.
      Demographic and anthropometric data, previous illnesses and measures of
      cardiovascular risk and kidney function were collected from electronic medical
      records. We determined the prevalence of occult CKD defined as patients with
      normal values of plasma creatinine (Cr) and reduced glomerular filtration rate
      (GFr) (< 60 ml/min/1,73 m(2)). The GFr was determined by the Modification of Diet
      in Renal Disease (MDRD) equation. RESULTS: The sample consisted of 3,197
      patients, the mean age was 67.7 years (SD = 11.7) and 53.9% were men. The
      prevalence of CKD according to the MDMR values was 16.6% (n = 532), of which
      60.3% (n = 321) corresponded to occult CKD. 6.6% (n = 211) of the participants
      had CKD with high Cr values. Multivariate analysis showed an association of
      occult CKD with female sex (OR = 2.7; CI 95% = 1,83-3,99). Occult CKD was
      associated with age, blood pressure higher than 150/100 mm/Hg and with a history
      of ischemic heart disease, heart failure, peripheral arterial disease and
      dyslipemia. CONCLUSIONS: The prevalence of CKD is 16.6%, of which 60.3% (n = 321)
      corresponds to occult CKD. Female sex is associated with the presence of occult
      CKD.

PMID- 20056256
TI  - [Demands and complaints in the clinical interview, key concepts for a safer
      clinical practice].

PMID- 20056257
TI  - [Clinicopathological approach to pre-invasive breast cancer ].

PMID- 20056258
TI  - [Necrotizing fasciitis due to Streptococcus pneumoniae].

PMID- 20056259
TI  - [Philosophy, medicine and clinical reasoning. Part II].

PMID- 20056260
TI  - [Treatment of symptomatic degenerative lumbar spinal stenosis by a percutaneous
      stand-alone lumbar interspinous implant. Preliminary experience with the Aperius
      device].
AB  - BACKGROUND AND PURPOSE: Surgery for degenerative spinal stenosis classically
      involves decompression by laminectomy or foraminotomy. The use of interspinous
      process devices has been described for these indications in recent years. This
      study evaluates the efficacy and morbidity of a percutaneous interspinous device
      to define whether this technique would be a suitable alternative to classical
      surgery. METHOD: Twenty-two patients with degenerative lumbar spinal stenosis
      were studied prospectively. Pre- and postoperative symptoms were assessed using
      the Visual Analogic Score (VAS), the Zurich Claudication Questionnaire (ZCQ),
      physical activity, and patient satisfaction. The implant was positioned under
      biplanar fluoroscopic control after progressive distraction of the interspinous
      space using trocars. The patients were reviewed after 7 days, 6 weeks, and 6
      months. RESULTS: All patients showed improved gait perimeter: 90 % could walk
      more than 1000 m 6 months after surgery, whereas only 50 % could walk this
      distance preoperatively. The mean symptom severity scores of 2.71 and physical
      activity scores of 2.38 improved to 1.87 (p=0.0003) and 1.53 (p<0.0001),
      respectively, after 6 months. The VAS decreased 3.5 points (p=0.0008) 6 months
      after surgery for leg pain. Ninety-one percent of the patients declared they were
      satisfied with the operation. CONCLUSION: The Aperius stand-alone and
      percutaneous interspinous device proved to be effective and safe in treating
      symptomatic lumbar spinal stenosis. This could be a good alternative to classic
      decompression surgery, but long-term follow-up studies are needed as well as
      subgroup analysis to define which patients could benefit from this technique.

PMID- 20056261
TI  - Triterpene glycosides from Agrostemma gracilis.
AB  - Four triterpene saponins, agrostemmosides A-D were isolated from the methanol
      extract of Agrostemma gracilis. The structures of the compounds were determined
      as 3-O-beta-D-xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)
      [beta-D-xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D
      xylopyranosyloleanolic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D
      xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester,
      3-O-beta-D-xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-beta
      D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester, 3-O-beta-D
      xylopyranosylechinocystic acid 28-O-beta-D-glucopyranosyl-(1-->2)-[beta-D
      xylopyranosyl-(1-->6)]-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl ester
      by a combination of one- and two-dimensional NMR techniques, and mass
      spectrometry. To the best of our knowledge this is the first phytochemical report
      on A. gracilis, and echinocystic acid saponins were encountered for the first
      time in Caryophyllaceae family.

PMID- 20056262
TI  - Biosynthetic origin of the saw-toothed profile in delta(13)C and delta(2)H of n
      alkanes and systematic isotopic differences between n-, iso- and anteiso-alkanes
      in leaf waxes of land plants.
AB  - The n-fatty acids containing an even number of carbons (ECN-n-FAs) in higher
      plants are biosynthesised by repetitive addition of a two carbon unit from
      malonyl-ACP. The n-alkanes containing an odd number of carbon atoms (OCN-n
      alkanes) are generally formed by the decarboxylation of ECN-n-FAs, but it is
      unknown how the less abundant even-carbon-numbered alkanes (ECN-n-alkanes) are
      biosynthesised in higher plants. There is a distinctive compositional pattern of
      incorporation of stable carbon ((13)C) and hydrogen ((2)H) isotopes in co
      existing ECN- and OCN-n-alkanes in leaves of higher plants, such that the OCN n
      alkanes are relatively enriched in (13)C but relatively depleted in (2)H against
      the ECN-n-alkanes. This is consistent with the OCN-n-fatty acids having a
      propionate precursor which is derived from reduction of pyruvate. A tentative
      pathway is presented with propionate produced by enzymatic reduction of pyruvate
      which is then thio-esterified with CoSH (coenzyme A thiol) in the chloroplast to
      form the terminal precursor molecule propionyl-CoA. This is then repetitively
      extended/elongated with the 2-carbon unit from malonyl-ACP to form the long chain
      OCN-n-fatty acids. The anteiso- and iso-alkanes in Nicotiana tabacum leaf waxes
      have previously been found to be systematically enriched in (13)C compared with
      the n-alkanes by Grice et al. (2008). This is consistent with the isotopic
      composition of their putative respective precursors (pyruvate as precursor for n
      alkanes, valine for iso-alkanes and isoleucine for anteiso-alkanes). The current
      study complements that of Grice et al. (2008) and looks at the distribution of
      hydrogen isotopes. The n-alkanes were found to be more enriched in deuterium
      ((2)H) than the iso-alkanes which in turn were more enriched than the anteiso
      alkanes. We propose therefore that the depletion of (2)H in the iso-alkanes,
      relative to the n-alkanes is the consequence of accepting highly (2)H-depleted
      hydrogen atoms from NADPH during their biosynthesis. The anteiso-alkanes are
      further depleted again because there are three NADPH-derived hydrogen atoms in
      their precursor isoleucine, as compared with only one NADPH-derived hydrogen in
      valine, the precursor of the iso-alkanes.

PMID- 20056263
TI  - Anxiety and depression in psychogenic movement disorder and non-epileptic
      seizures: a prospective comparative study.
AB  - OBJECTIVE: This study compared anxiety and depression in patients presenting with
      psychogenic non-epileptic seizures (PNES) with those suffering from psychogenic
      movement disorders (PMD) to assess the link between these psychiatric pathologies
      and neurological symptoms. METHODS: This clinically descriptive, prospective
      study involved consecutive patients who fulfilled the clinical and video-EEG
      criteria for PNES and PMD, and who were recruited over an 18-month period. Semi
      structured (according to DSM-IV criteria) psychiatric interviews and self
      evaluation using the Beck Depression Inventory and Spielberger State-Trait
      Anxiety Inventory were carried out. Clinical follow-up was conducted 8-12 months
      after the first evaluation. RESULTS: A total of 17 patients were recruited: nine
      presented with PNES; and eight had PMD. Both patient groups had similar
      demographic and clinical data as well as depression and personality disorders.
      Although not statistically significant, there was a trend towards an increased
      prevalence of a familial medical history of epilepsy and a higher incidence of
      anxiety disorders among patients with PNES. CONCLUSION: The data from this
      prospective study underscore the clinical and psychiatric similarity between PNES
      and PMD patients. Further studies involving a larger number of subjects should
      confirm, from a statistical point of view, the differences suggested in the
      present investigation and, in particular, the greater incidence of anxiety
      disorders in PNES patients and the presence of an epileptic parent as a risk
      factor for PNES.

PMID- 20056264
TI  - The degradation of microcystin-LR using doped visible light absorbing
      photocatalysts.
AB  - Microcystins are one of the primary hepatotoxic cyanotoxins released from
      cyanobacteria. The presence of these compounds in water has resulted in the death
      of both humans and domestic and wild animals. Although microcystins are
      chemically stable titanium dioxide photocatalysis has proven to be an effective
      process for the removal of these compounds in water. One problem with this
      process is that it requires UV light and therefore in order to develop effective
      commercial reactor units that could be powered by solar light it is necessary to
      utilize a photocatalyst that is active with visible light. In this paper we
      report on the application of four visible light absorbing photocatalysts for the
      destruction of microcystin-LR in water. The rhodium doped material proved to be
      the most effective material followed by a carbon-modified titania. The
      commercially available materials were both relatively poor photocatalysts under
      visible radiation while the platinum doped catalyst also displayed a limited
      activity for toxin destruction.

PMID- 20056265
TI  - Effects of alcohol administration during adulthood on parvalbumin and glial
      fibrillary acidic protein immunoreactivity in the rat cerebral cortex.
AB  - The pathology of brain atrophy mediated by alcohol was investigated in all parts
      of the cerebral cortex (the frontal, parietal, temporal lobes and occipital
      cortex) by using two markers: parvalbumin (PV) and glial fibrillary acidic
      protein (GFAP). Three-month old male Wistar rats were divided into control (C)
      and alcohol-exposed groups. The control group received distilled water, whereas
      the alcohol-exposed groups received either a low dose (2g/kg body wt) or a high
      dose (5g/kg) of ethanol for periods of 21 days, 3 or 6 months. The brains of the
      animals were processed for immunohistochemistry using anti-parvalbumin and anti
      GFAP antibodies and the number of PV immunoreactive (PV-ir) neurons and GFAP
      immunoreactive (GFAP-ir) astrocytes were counted per unit area. Results showed
      that all groups exposed to ethanol had significantly reduced numbers of PV-ir
      neurons in all parts of the cerebral cortex compared to those of the control
      group (p<0.05). In contrast, the numbers of GFAP-ir astrocytes were increased in
      all parts of the cerebral cortex following the exposure to a high dose of ethanol
      after 21-days (but not a low dose) and both high and low doses of ethanol after 3
      months or 6-months treatment compared to those of age-matched control groups
      (p<0.05). This indicated that in young rats (21-days), PV-ir neurons in all
      cerebral cortex areas seemed to be more sensitive to alcohol than GFAP-ir
      astrocytes. Moreover, the change in densities of both PV-ir neurons and GFAP-ir
      astrocytes became more apparent after exposure to prolonged and high doses of
      ethanol. The decrease of PV-ir neurons and the increase of GFAP-ir astrocytes
      indicated that alcohol may induce pathology in broad areas of the cerebral
      cortex. This may explain the underlying mechanism of brain atrophy and other
      impairments found in alcoholics. For investigations of the effects of alcohol on
      mediating brain pathology, we recommend the use of the two markers (PV and GFAP).

PMID- 20056266
TI  - Achievements and unmet needs in the management of advanced ovarian cancer.
AB  - Ovarian cancer is the second most common gynaecological malignancy, and
      represents the leading cause of gynecologic cancer-related death in Europe and
      United States. The majority of the cases are in fact diagnosed in advanced stage,
      with limited chance to be cured. Optimal management of advanced ovarian cancer
      includes histopathological diagnosis, accurate surgical staging, debulking
      surgery and platinum-based chemotherapy. The combination of carboplatin and
      paclitaxel is commonly recognised as the standard regimen because of tolerability
      and activity. Intraperitoneal chemotherapy provides superior efficacy results,
      but its use is still controversial because of poor tolerability and compliance.
      Unfortunately, despite its chemosensitivity, the majority of ovarian cancer
      patients, including those who achieve a complete response to first-line
      chemotherapy, will relapse and eventually die. Among the strategies to improve
      patient outcome, maintenance therapy has failed to show a consistent benefit
      across clinical trials. Salvage second-line therapy is generally based on
      rechallenge with platinum in patients with platinum sensitive disease. Patients
      with platinum resistant/refractory might benefit from liposomal doxorubicin or
      topotecan. Other active cytotoxics include docetaxel, gemcitabine, etoposide and
      vinorelbine as well as epothilone derivatives such as patupilone which is still
      in development. Among targeted agents, the antiangiogenic agent bevacizumab seems
      extremely promising and is actively investigated in combination with first-line
      chemotherapy. More recently, interesting results have been obtained with the
      inhibitors of poly-ADP-ribose polymerase (PARP) in patients with BRCA-mutated
      tumors.

PMID- 20056267
TI  - The relationship of VEGF polymorphisms with serum VEGF levels and progression
      free survival in patients with epithelial ovarian cancer.
AB  - OBJECTIVE: The vascular endothelial growth factor (VEGF) is an important
      regulator of angiogenesis and vascular permeability of tumors. In the present
      study we evaluated the relation of five single nucleotide polymorphisms (SNPs) in
      the VEGF gene with progression-free survival. Furthermore, we evaluated the
      functional significance of the SNPs as determined by the influence on serum VEGF
      levels in ovarian cancer. METHODS: Serum from 143 consecutive ovarian cancer
      patients referred for first line platinum/paclitaxel treatment were analyzed for
      serum VEGF levels using commercially available enzyme-linked immunosorbent assay
      (ELISA). VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C and
      +936C/T) were determined by real time PCR using genomic DNA extracted from whole
      blood samples. RESULTS: VEGF serum levels were significantly higher in carriers
      of the 2578C, 460T and 405C, alleles compared to non-carriers (p=0.003, p=0.003
      and p=0.001, respectively). There was no significant correlation between VEGF SNP
      genotypes and progression-free survival. In haplotype analysis, the multivariate
      survival analysis showed that progression-free survival (PFS) for the patients
      with the AGCGC haplotype was significantly improved compared to patients with
      other haplotypes (HR 1.9, p=0.036). CONCLUSIONS: VEGF polymorphisms were found to
      be significantly related with serum VEGF levels. The AGCGC haplotype was found to
      be independently associated with improved PFS.

PMID- 20056268
TI  - Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro
      proliferation, invasion, and matrix metalloproteinase activity.
AB  - OBJECTIVES: Lysophosphatidic acid (LPA) has potent growth-regulatory effect in
      many cell types and has been linked to the in vivo tumor growth and metastasis in
      several malignancies. The goal of this study was to assess the regulation of (EC)
      microenvironment by LPA through the examination of its effect on cell
      proliferation, migration, invasion, uPA activity, and matrix metalloproteinase
      (MMP) secretion/activation. METHODS: All experiments were performed in vitro
      using an EC cell line, HEC-1A. Cell proliferation was determined using the
      Promega MTS proliferation assay following 48 h of exposures to different
      concentrations of LPA (0.1, 1.0 and 10.0 microM). Cell invasion was assessed
      using a modified Boyden chamber assay with collagen I coated on the membrane. HEC
      1A motility was examined by Boyden chamber migration assay as well as the scratch
      wound closure assay on type I collagen. MMP secretion/activation in HEC-1A
      conditioned medium was detected by gelatin zymography. MMP-7 mRNA expression was
      determined using real-time PCR. uPA activity was measured using a coupled
      colorimetric assay. RESULTS: LPA, at the concentrations of 0.1 and 1.0 microM,
      significantly induced the proliferation of HEC-1A cells (p<0.01). At 10 microM,
      LPA- induced HEC-1A proliferation to a less extent and showed no significant
      effect on HEC-1A invasion and migration (p>0.05). Gelatin zymogram showed that
      HEC-1A cells secreted high levels of MMP-7, while MMP-2 and MMP-9 are barely
      detectable. In addition, LPA significantly enhanced uPA activity in HEC-1A
      conditioned medium in a concentration-dependent manner. CONCLUSIONS: LPA is a
      potent modulator of cellular proliferation and invasion for EC cells. It also has
      the capacity to stimulate the secretion/activity of uPA and MMP-7. Those results
      suggest that LPA is a bioactive modulator of EC microenvironment and may have a
      distinct regulation mechanism as observed in epithelial ovarian cancer.

PMID- 20056269
TI  - Microencapsulation of canine sperm and its preservation at 4 degrees C.
AB  - The objective of this study was to develop a preservation method for canine sperm
      using microencapsulation. Pooled ejaculates from three beagles (Canis familiaris)
      were extended in egg yolk Tris extender and were encapsulated in gel (alginate
      only) or polycation (poly-L-lysine membrane bound) microcapsules at 0.75% and
      1.0% alginate concentration. In Experiment 1, characteristics of microcapsule and
      microencapsulated sperm were evaluated during chilling storage for 48 h. Gel
      microcapsules at 0.75% alginate concentration had a teardrop-like structure with
      fragility, whereas those at 1.0% alginate had a solid spherical structure. In all
      groups, diameter of the microcapsules increased with duration of storage
      (P<0.05). Alginate concentration did not affect the sperm recovery rate from
      microcapsules. Total average recovery rate of sperm from polycation microcapsules
      was lower than that of gel microcapsules (P<0.05). Progressive motility of
      polycation microencapsulated sperm and unencapsulated sperm (control) was higher
      than that of the gel microencapsulated sperm, both at 0.75% and 1.0% alginate
      concentration (P<0.05), although viability of sperm was similar among the three
      groups. In Experiment 2, to evaluate the sperm longevity after chilling storage,
      sperm were microencapsulated in polycation microcapsules at 1.0% alginate
      concentration, stored at 4 degrees C for 0, 1, 4, and 7 d, and then cultured at
      38.5 degrees C for 0, 6, and 24h. Progressive motility and viability of
      microencapsulated sperm were higher than those of unencapsulated spermatozoa at 0
      to 24h of culture after 4 and 7 d of chilling storage (P<0.05). In conclusion,
      polycation microencapsulation at 1.0% alginate concentration can be successfully
      applied for chilling storage of canine sperm by maintaining motility and
      viability for up to 7 d.

PMID- 20056270
TI  - Impact of replacing Bis-GMA and TEGDMA by other commercially available monomers
      on the properties of resin-based composites.
AB  - PURPOSE: To evaluate important material properties of six experimental resin
      based restorative materials (EXP) with systematically modified resin matrices
      using conventional and alternative monomers in comparison with an experimental
      standard (ST). MATERIALS AND METHODS: Commercially available monomers were
      selected according to their molecular weight, functionality, viscosity, and
      polymerization shrinkage. ST, 71wt% filler, matrix UDMA/Bis-GMA/TTEGDMA and six
      EXPs with modified organic matrices but the same filler content were
      manufactured. Flexural strength, flexural modulus, water sorption, solubility and
      polymerization shrinkage of all EXPs were measured and compared with the results
      of ST. RESULTS: ANOVA (p<0.05) revealed significant differences among the
      materials and all investigated properties. Bis-GMA and UDMA were substituted by
      alternative monomers without losing flexural strength or modulus. Replacing the
      diluting monomer TTEGDMA with alternative monomers resulted in increased flexural
      strength. None of the experimental products with modified matrices showed
      increased water sorption or solubility but some even performed better than ST.
      Increased hygroscopic expansion and reduced shrinkage were achieved using a very
      hydrophilic monomer but no significant differences of water sorption and
      solubility in comparison with ST were found. CONCLUSION: The results indicated
      that there are monomers commercially available providing the same or even better
      properties than conventional matrices.

PMID- 20056271
TI  - Strategies for cell manipulation and skeletal tissue engineering using high
      throughput polymer blend formulation and microarray techniques.
AB  - A combination of high-throughput material formulation and microarray techniques
      were synergistically applied for the efficient analysis of the biological
      functionality of 135 binary polymer blends. This allowed the identification of
      cell-compatible biopolymers permissive for human skeletal stem cell growth in
      both in vitro and in vivo applications. The blended polymeric materials were
      developed from commercially available, inexpensive and well characterised
      biodegradable polymers, which on their own lacked both the structural
      requirements of a scaffold material and, critically, the ability to facilitate
      cell growth. Blends identified here proved excellent templates for cell
      attachment, and in addition, a number of blends displayed remarkable bone-like
      architecture and facilitated bone regeneration by providing 3D biomimetic
      scaffolds for skeletal cell growth and osteogenic differentiation. This study
      demonstrates a unique strategy to generate and identify innovative materials with
      widespread application in cell biology as well as offering a new reparative
      platform strategy applicable to skeletal tissues.

PMID- 20056272
TI  - A hydrogel-based stem cell delivery system to treat retinal degenerative
      diseases.
AB  - Regenerative strategies for retinal degenerative diseases are limited by poor
      cellular survival, distribution and integration after transplantation to the sub
      retinal space. To overcome this limitations a stem cell delivery system was
      developed, taking advantage of the minimally-invasive, injectable and
      biodegradable properties of a blend of hyaluronan and methylcellulose (HAMC). The
      physical and biological properties of this unique HAMC formulation were studied.
      HAMC supported retinal stem-progenitor cell (RSPC) survival and proliferation in
      vitro. The blend was a viscous solution, exhibiting properties ideal for delivery
      to the sub-retinal space. In vivo transplantation studies in mice were carried
      out to investigate both the biodegradability of HAMC in the sub-retinal space
      over 7 days and the potential of HAMC as a cell delivery vehicle. RSPCs delivered
      in HAMC were more evenly distributed in the sub-retinal space than those
      delivered in traditional saline solutions, suggesting that HAMC is a promising
      vehicle for cellular delivery to the degenerating retina overcoming previously
      reported barriers to tissue integration in the retina such as cellular
      aggregation and non-contiguous distribution.

PMID- 20056273
TI  - Physical surface and electromechanical properties of doped polypyrrole
      biomaterials.
AB  - Conducting polymers doped with biomolecules (biodopants) are becoming more widely
      evaluated for use as biomaterials. The use of biodopants is intended to enhance
      the compatibility of the polymers, however their effect on the physical
      properties of the final composite material has generally been less of a
      consideration. Here, we have characterised the physical surface properties of
      polypyrrole substrates doped with extracellular matrix and non-biological
      molecules using Atomic Force Microscopy (AFM) and Electrochemical AFM (EC-AFM)
      techniques. The physical parameters of the differently doped films ranged between
      5 and 32 nm for the RMS roughness, 30-1000 MPa for the Young's modulus, and 1.6
      4.7% for the actuation strain. It was found that irrespective of whether the
      dopant was biologically derived, the physical properties tended to group together
      with films having either a low roughness, low modulus and high strain, or vice
      versa. When compared to our previous study, which investigated these polymers as
      potential biomaterials for supporting the growth and differentiation of skeletal
      muscle cells, these two groupings of the parameters correlated with the differing
      ability of the polypyrrole substrates to support the cells. Thus, in addition to
      the chemical advantage gained from using biodopants, the resulting physical
      properties of the polymer material should also be considered in their design as
      biomaterials for tissue engineering applications.

PMID- 20056274
TI  - A Streptococcus pyogenes derived collagen-like protein as a non-cytotoxic and non
      immunogenic cross-linkable biomaterial.
AB  - A range of bacteria have been shown to contain collagen-like sequences that form
      triple-helical structures. Some of these proteins have been shown to form triple
      helical motifs that are stable around body temperature without the inclusion of
      hydroxyproline or other secondary modifications to the protein sequence. This
      makes these collagen-like proteins particularly suitable for recombinant
      production as only a single gene product and no additional enzyme needs to be
      expressed. In the present study, we have examined the cytotoxicity and
      immunogenicity of the collagen-like domain from Streptococcus pyogenes Scl2
      protein. These data show that the purified, recombinant collagen-like protein is
      not cytotoxic to fibroblasts and does not elicit an immune response in SJL/J and
      Arc mice. The freeze dried protein can be stabilised by glutaraldehyde cross
      linking giving a material that is stable at >37 degrees C and which supports cell
      attachment while not causing loss of viability. These data suggest that bacterial
      collagen-like proteins, which can be modified to include specific functional
      domains, could be a useful material for medical applications and as a scaffold
      for tissue engineering.

PMID- 20056275
TI  - Negative regulation of Ca(2+) influx during P2Y(2) purinergic receptor activation
      is mediated by Gbetagamma-subunits.
AB  - We have previously reported that P2Y(2) purinoceptors and muscarinic M(3)
      receptors trigger Ca(2+) responses in HT-29 cells that differ in their
      timecourse, the Ca(2+) response to P2Y(2) receptor activation being marked by a
      more rapid decline of intracellular Ca(2+) concentration ([Ca(2+)](i)) after the
      peak response and that this rapid decline of [Ca(2+)](i) was slowed in cells
      expressing heterologous beta-adrenergic receptor kinase (betaARK). In the present
      study, we demonstrate that, during P2Y(2) receptor activation, betaARK expression
      increases the rate of Gd(3+)-sensitive Mn(2+) influx, a measure of the rate of
      store-operated Ca(2+) entry from the extracellular space, during P2Y(2)
      activation and that this effect of betaARK is mimicked by exogenous alpha
      subunits of G(q), G(11) and G(i2). The effect of betaARK on the rate of Mn(2+)
      influx is thus attributable to its ability to scavenge G protein betagamma
      subunits released during activation of P2Y(2) receptor. We further find that the
      effect of betaARK on the rate of Mn(2+) influx during P2Y(2) receptor activation
      can be overcome by arachidonic acid. In addition, the UTP-induced Mn(2+) influx
      rate was significantly increased by inhibitors of phospholipase A(2) (PLA(2)) and
      an siRNA directed against PLA(2)beta, but not by an siRNA directed against
      PLA(2)alpha or by inhibitors of arachidonic acid metabolism. These findings
      provide evidence for the existence of a P2Y(2) receptor-activated signalling
      system that acts in parallel with depletion of intracellular Ca(2+) stores to
      inhibit Ca(2+) influx across the cell membrane. This signalling process is
      mediated via Gbetagamma and involves PLA(2)beta and arachidonic acid.

PMID- 20056276
TI  - Placement decisions and disparities among aboriginal groups: an application of
      the decision making ecology through multi-level analysis.
AB  - OBJECTIVE: This paper examined the relative influence of clinical and
      organizational characteristics on the decision to place a child in out-of-home
      care at the conclusion of a child maltreatment investigation. It tested the
      hypothesis that extraneous factors, specifically, organizational characteristics,
      impact the decision to place a child in out-of-home care. A secondary aim was to
      identify possible decision making influences related to disparities in placement
      decisions tied to Aboriginal children. Research suggests that the Aboriginal
      status of the child and structural risk factors affecting the family, such as
      poverty and poor housing, substantially account for this overrepresentation.
      METHODS: The decision to place a child in out-of-home care was examined using
      data from the Canadian Incidence Study of Reported Child Abuse and Neglect. This
      child welfare dataset collected information about the results of nearly 5,000
      child maltreatment investigations as well as a description of the characteristics
      of the workers and organization responsible for conducting those investigations.
      Multi-level statistical models were developed using MPlus software, which can
      accommodate dichotomous outcome variables, which are more reflective of decision
      making in child welfare. MPlus allows the specific case of the logistic link
      function for binary outcome variables under maximum likelihood estimation.
      RESULTS: Final models revealed the importance of the number of Aboriginal reports
      to an organization as a key second level predictor of the placement decision. It
      is the only second level factor that remains in the final model. This finding was
      very stable when tested over several different levels of proportionate caseload
      representation ranging from greater than 50% to 20% of the caseload. CONCLUSIONS:
      Disparities among Aboriginal children in child welfare decision making were
      identified at the agency level. PRACTICE IMPLICATIONS: The study provides
      additional evidence supporting the possibility that one source of
      overrepresentation of Aboriginal children in the Canadian foster care system is a
      lack of appropriate resources at the agency or community level.

PMID- 20056277
TI  - Reporting air emissions from animal production activities in the United States.
AB  - Major releases of airborne ammonia and hydrogen sulfide from the decomposition of
      animal waste have the American public concerned about the health of persons near
      farms. Emissions of these hazardous substances are regulated by the US
      Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA)
      and the Emergency Planning and Community Right-to-Know Act (EPCRA). Moreover,
      federal regulatory provisions delineate thresholds for reporting hazardous
      pollutants being released into the air. In 2008, the US Environmental Protection
      Agency (EPA) adopted a reporting exemption under which all farms were exempted
      from reporting air emissions under CERCLA and small farms were exempted under
      EPCRA. The US EPA's exemption poses questions about whether the rule is contrary
      to congressional mandates. Environmental and industry groups have challenged this
      exemption in federal circuit court, and the judiciary will need to decide whether
      the agency had authority to adopt the rule. To accord protection to humans from
      hazardous airborne emissions from farms producing livestock, state agencies may
      want to adopt scientifically-justified ambient air quality standards.

PMID- 20056278
TI  - Positioning the image of AIDS.
AB  - AIDS posters can be treated as material objects whose production, distribution
      and consumption varied across time and place. It is also possible to reconstruct
      and analyse the public health discourse at the time these powerful images
      appeared. More recently, however, these conventional historical approaches have
      been challenged by projects in literary and art criticism. Here, images of AIDS
      are considered in terms of their function in and for a new discursive regime of
      power centred on the human body and its visualization. How images of AIDS came to
      be understood in Western culture in relation to wider political and economic
      conditions redefines the historical task.

PMID- 20056279
TI  - The first iron(III) complexes with cyclin-dependent kinase inhibitors: Magnetic,
      spectroscopic (IR, ES+ MS, NMR, (57)Fe Mossbauer), theoretical, and biological
      activity studies.
AB  - The first Fe(III) complexes 1-6 with cyclin-dependent kinase (CDK) inhibitors of
      the type [Fe(L(n))Cl(3)].nH(2)O (n=0 for 1, 1 for 2, 2 for 3-6; L(1)-L(6)=C2- and
      phenyl-substituted CDK inhibitors derived from 6-benzylamino-9-isopropylpurine),
      have been synthesized and characterized by elemental analysis, IR, (57)Fe
      Mossbauer, (1)H and (13)C NMR, and ES+ mass spectroscopies, conductivity and
      magnetic susceptibility measurements, and thermogravimetric analysis (TGA) and
      differential scanning calorimetry (DSC). The study revealed that the compounds
      are mononuclear, tetrahedral high-spin (S=5/2) Fe(III) complexes with an
      admixture of an S=3/2 spin state originating probably from five-coordinated
      Fe(III) ions either connecting with a bidentate coordination mode of the CDK
      inhibitor ligand or relating to the possibility that one crystal water molecule
      enters the coordination sphere of the central atom in a portion of molecules of
      the appropriate complex. Nearly spin-only value of the effective magnetic moment
      (5.82micro(eff)/micro(B)) was determined for compound 1 due to absence of crystal
      water molecule(s) in the structure of the complex. Based on NMR data and DFT
      calculations, we assume that the appropriate organic ligand is coordinated to the
      Fe(III) ion through the N7 atom of a purine moiety. The cytotoxicity of the
      complexes was tested in vitro against selected human cancer cell lines (G-361,
      HOS, K-562 and MCF-7) along with the ability to inhibit the CDK2/cyclinE kinase.
      The best cytotoxicity (IC(50): 4-23muM) and inhibition activity (IC(50): 0.02
      0.09microM) results have been achieved in the case of complexes 2-4, and
      complexes 3, 4 and 6, respectively. In addition, the X-ray structure of 2-chloro
      6-benzylamino-9-isopropylpurine, i.e. a precursor for the preparation of L(1),
      L(4) and L(5), is also described.

PMID- 20056280
TI  - Synthesis, crystal structure, characterization of zinc(II), cadmium(II) complexes
      with 3-thiophene aldehyde thiosemicarbazone (3TTSCH). Biological activities of
      3TTSCH and its complexes.
AB  - The reaction of zinc(II) chloride, cadmium(II) chloride and bromide with 3
      thiophene aldehyde thiosemicarbazone leads to the formation of a series of new
      complexes. They have been characterized by spectroscopic studies: infrared, (1)H
      NMR, and electronic spectra. The crystal structures of the compound
      [ZnCl(2)(3TTSCH)(2)] and [CdBr(2)(3TTSCH)(2)] have been determined by X-ray
      diffraction methods. For the complexes [ZnCl(2)(3TTSCH)(2)] and
      [CdBr(2)(3TTSCH)(2)], the central ion is coordinated through the sulfur, and for
      the complexes [CdCl(2)(3TTSCH)], [CdBr(2)(3TTSCH)] the ion is coordinated through
      the sulfur as well as azomethine nitrogen atom of the thiosemicarbazone. In
      addition, fungistatic and bacteriostatic activities of both ligand and complexes
      have been evaluated. Cadmium(II) complexes have shown the most significant
      activities.

PMID- 20056281
TI  - Modulation of the active site conformation by site-directed mutagenesis in
      cytochrome c oxidase from Paracoccus denitrificans.
AB  - The structural and functional properties of active site mutants of cytochrome c
      oxidase from Paracoccus denitrificans (PdCcO) were investigated with resonance
      Raman spectroscopy. Based on the Fe-CO stretching modes and low frequency heme
      modes, two conformers (alpha- and beta-forms) were identified that are in
      equilibrium in the enzyme. The alpha-conformer, which is the dominant species in
      the wild-type enzyme, has a shorter heme a(3) iron-Cu(B) distance and a more
      distorted heme, as compared to the beta-conformer, which has a more relaxed and
      open distal pocket. In general, the mutations caused a decrease in the population
      of the alpha-conformer, which is concomitant with a decreased in the catalytic
      activity, indicating that the alpha-conformer is the active form of the enzyme.
      The data suggest that the native structure of the enzyme is in a delicate balance
      of intramolecular interactions. We present a model in which the mutations
      destabilize the alpha-conformer, with respect to the beta-conformer, and raise
      the activation barrier for the inter-conversion between the two conformers. The
      accessibility of the two conformers in the conformational space of CcO plausibly
      plays a critical role in coupling the redox reaction to proton translocation
      during the catalytic cycle of the enzyme.

PMID- 20056282
TI  - Four new copper(II) complexes with 1,3-tpbd ligand: Synthesis, crystal
      structures, magnetism, oxidative and hydrolytic cleavage of pBR322 DNA.
AB  - Four copper(II) complexes [Cu(2)(1,3-tpbd)Cl(4)].EtOH (1), {[Cu(2)(1,3-tpbd)(mu
      Cl)(2)](ClO(4))(2)(H(2)O)(4.5) (NaClO(4))}(infinity) (2), [Cu(2)(1,3-tpbd)(1,10
      phen)(2)(H(2)O)(2)](ClO(4))(4) (3) and [Cu(2)(1,3-tpbd)(2,2'
      bpy)(2)(H(2)O)(2)](ClO(4))(4) (4) (1,3-tpbd=N,N,N',N'-tetrakis(2
      pyridylmethyl)benzene-1,3-diamine) have been synthesized and characterized by X
      ray single crystal structure analysis. Variable-temperature magnetic
      susceptibility studies (2-300K) indicate the existence of antiferromagnetic
      coupling between the copper(II) ions in complexes 2 and 3. The interactions of
      the four complexes with calf thymus DNA (CT-DNA) have been investigated by UV
      absorption, fluorescent spectroscopy, circular dichroism spectroscopy, viscosity
      and cyclic voltammetry, and the modes of CT-DNA binding to the complexes have
      been proposed. Furthermore, DNA cleavage activities by the four complexes were
      performed in the presence and absence of external agents, the results indicate
      that their cleavage activities have been promoted in the presence of external
      agents. Mechanism investigation shows that the four complexes could cleave DNA
      through both oxidative and hydrolytic processes. In the four copper(II)
      complexes, complex 2 showed highest cleavage activity with the pseudo-Michaelis
      Menten kinetic paraments k(cat)=5.16h(-1) and K(m)=3.6x10(-5)M.

PMID- 20056283
TI  - Parental depression and child temperament: assessing child to parent effects in a
      longitudinal population study.
AB  - Current research supports a link between maternal depression and difficult child
      temperament. The direction of effect is often assumed to be from parent to child,
      but few studies have addressed child to parent effects. In a large cohort study,
      the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=14663), we aimed
      to further existing knowledge by investigating the relationship between maternal
      and paternal depressive symptoms and child temperament, and determining the
      direction of any effects found. Data was collected at 2 time-points (when the
      children were 6 and 24 months old), using the Edinburgh Postnatal Depression
      Scale and the Mood and Intensity subscales of the Carey Temperament Scales.
      Significant parent to child effects were seen, with maternal and paternal
      depressive symptoms at Time 1 leading to more difficult temperament at Time 2.
      Father to child effects were significant only in male children. Little evidence
      was found for child to parent effects.

PMID- 20056284
TI  - Lipopolysaccharide and TNF-alpha modify adenosine A(2A) receptor expression and
      function in equine monocytes.
AB  - Stimulation of adenosine A(2A) receptors results in anti-inflammatory effects in
      a variety of cell types. Lipopolysaccharide (LPS) and pro-inflammatory cytokines,
      such as TNF-alpha and IL-1, have been reported to up-regulate the expression of
      adenosine A(2A) receptors and thereby enhance the functional activity of
      adenosine A(2A) receptors in human and murine monocyte/macrophage cell lines and
      in monocytes/macrophages isolated from those species. In this study, we
      investigated the effects of LPS and TNF-alpha on the expression and functional
      activity of adenosine A(2A) receptors in isolated equine peripheral blood
      monocytes. The results of this study indicate that LPS and TNF-alpha up-regulate
      the transcription of adenosine A(2A) receptors for up to 24h; the response to LPS
      was of greater magnitude than the response to TNF-alpha. In this study,
      incubation with LPS, but not with TNF-alpha, resulted in down-regulation of
      adenosine A(3) receptor mRNA expression. Furthermore, incubation of these cells
      with LPS significantly increases the surface density of adenosine A(2A)
      receptors, and incubation with low concentrations of either LPS or TNF-alpha
      significantly increases the potency of the adenosine A(2A) receptor agonist,
      ATL313, to inhibit LPS-induced production of TNF-alpha. These findings suggest
      that the increased expression of adenosine A(2A) receptors and the enhanced
      functional potency of adenosine A(2A) receptor agonists after exposure to pro
      inflammatory substances such as LPS or TNF-alpha may render adenosine A(2A)
      receptor agonists particularly important in the treatment of the systemic
      inflammatory response syndrome that occurs secondary to endotoxemia and bacterial
      infections in adult horses and neonatal foals.

PMID- 20056285
TI  - The effects of total dissolved solids on egg fertilization and water hardening in
      two salmonids--Arctic Grayling (Thymallus arcticus) and Dolly Varden (Salvelinus
      malma).
AB  - Previous studies have indicated that salmonid fertilization success may be very
      sensitive to elevated concentrations of total dissolved solids (TDS) with effects
      at concentrations as low as 250mgl(-1) being reported. However, interpretation of
      these studies is complicated by poor control performance and variable
      concentration response relationships. To address this, a series of experiments
      were performed to evaluate TDS effects on Arctic Grayling (Thymallus arcticus)
      and Dolly Varden (Salvelinus malma) fertilization success and identify possible
      mechanisms for previously observed test variability and any observed effects of
      TDS. Results indicate that some of the experiments reported here were likely
      confounded by extended milt holding times prior to experiment initiation. Milt
      holding times >6h were shown to significantly reduce control fertilization and
      corresponding concentration response relationships were variable. When milt
      holding time was minimized during fertilization experiments, consistent control
      performance with >90% control fertilization was achieved and consistent
      concentration response relationships were observed for both species examined.
      Experiments performed under these conditions indicate that Arctic Grayling and
      Dolly Varden fertilization success is not sensitive to elevated TDS with EC20s
      (concentration causing 20% effect) of >2782 and >1817mgl(-1) (the highest
      concentrations tested), respectively. However, TDS was shown to significantly
      affect embryo water absorption during the water hardening phase immediately
      following fertilization. The lowest observable effect concentrations (LOECs) for
      this endpoint were 1402 and 964mgl(-1) for Arctic Grayling and Dolly Varden,
      respectively. The effect of reduced embryo turgidity, due to impaired water
      absorption, on resistance to mechanical damage under real world conditions needs
      further investigation in order to understand the implications of this observed
      effect.

PMID- 20056286
TI  - Can tissue engineering concepts advance tumor biology research?
AB  - Advances in tissue engineering have traditionally led to the design of scaffold-
      or matrix-based culture systems that better reflect the biological, physical and
      biochemical environment of the natural extracellular matrix. Although their
      clinical applications in regenerative medicine tend to receive most of the
      attention, it is obvious that other areas of biomedical research could be well
      served by the powerful tools that have already been developed in tissue
      engineering. In this article, we review the recent literature to demonstrate how
      tissue engineering platforms can enhance in vitro and in vivo models of
      tumorigenesis and thus hold great promise to contribute to future cancer
      research.

PMID- 20056287
TI  - Contemporary strategies in combating microbial contamination in food chain.
AB  - The objective of this review has been to disclose collected information on
      benefits and risks of selected "less-than - sterilizing" processes applied to
      control microbial hazards in food that was meticulously collected and critically
      reviewed during five years of EU Sixth framework project "Pathogen Combat". The
      target organisms of the project, and thus of this review, too, were Listeria
      monocytogenes, Escherichia coli O157:H7 and Campylobacter jejuni. Due to their
      specific response and high relevancy to the food safety, foodborne viruses and
      spores, were also discussed within the scope of this review. Selected treatments
      comprised High Pressure Processing, Intense Light Pulses, treatments with organic
      acids, treatments with chlorine dioxide and for their relevancy also mild heat
      treatments and Pulsed Electric Field processing were included. The main aspects
      included in this review were principles of the processes used and their
      application, sub-lethal injury and its consequences on microbial food safety, and
      legal platform and its impact on wide use of the treatments. Finally a reflection
      has been made to combined application of different hurdles and accompanying
      risks.

PMID- 20056288
TI  - Effects of exposure to poultry chemical decontaminants on the membrane fluidity
      of Listeria monocytogenes and Salmonella enterica strains.
AB  - There is a lack of work comparing the influence of various poultry chemical
      decontaminants on the membrane fluidity of pathogenic bacteria. In order to
      assess the possible role of physical membrane changes on bacterial adaptation to
      decontaminants, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH)
      was measured in Listeria monocytogenes and Salmonella enterica strains before and
      after growth in the presence of increasing sub-lethal concentrations of
      decontaminants (trisodium phosphate - TSP, acidified sodium chlorite - ASC,
      citric acid - CA and peroxyacids - PA). Higher (P<0.05) anisotropy values (lower
      membrane fluidity) were observed, both before and after exposure to
      decontaminants, in strains of L. monocytogenes (average 0.206+/-0.008) than in
      those of S. enterica (0.188+/-0.013). Cells exposed to sub-inhibitory
      concentrations of acid decontaminants (CA or PA) showed higher (P<0.05)
      anisotropy values and percentages of survival to acid stress than unexposed
      cells, suggesting that adaptation to these compounds is related to changes in
      membrane fluidity. Minimal changes in anisotropy values were observed after
      growth in presence of TSP or ASC. After treatment with strong concentrations of
      acid decontaminants (0.05 and 1% ASC, 5% and 10% CA, and 0.1 and 0.25% PA) the
      highest anisotropy values (highest membrane rigidity) were shown by cells
      previously grown with sub-inhibitory concentrations of CA or PA, suggesting that
      the synergistic effects of successive applications of various acids should be
      minimized. Because of the relationship between high membrane rigidity and high
      resistance to different stresses, the fact that it is essential to ensure
      adequate, inhibitory, CA or PA concentrations during poultry decontamination
      treatments is underlined.

PMID- 20056289
TI  - Viability of Lactobacillus acidophilus in synbiotic guava mousses and its
      survival under in vitro simulated gastrointestinal conditions.
AB  - The effects of refrigeration, freezing and substitution of milk fat by inulin and
      whey protein concentrate (WPC) on Lactobacillus acidophilus La-5 viability and
      resistance to gastric and enteric simulated conditions in synbiotic guava mousses
      effects were investigated. Refrigerated mousses supplemented with WPC presented
      the best probiotic viability, ranging from 7.77 to 6.24 log cfu/g during 28 days
      of storage. The highest probiotic populations, above 7.45 log cfu/g, were
      observed for all frozen mousses during 112 days of storage. Decreased L.
      acidophilus survival during the in vitro gastrointestinal simulation was observed
      both for refrigerated and frozen mousses. Nonetheless, for the refrigerated
      mousses, the addition of inulin enhanced the probiotic survival during the in
      vitro assays in the first week of storage. L. acidophilus survival in simulated
      gastrointestinal fluids was also improved through freezing. The frozen storage
      may be used to provide increased shelf-life for synbiotic guava mousses. Even
      though the protective effect of inulin and WPC on the probiotic microorganism
      tested was shown to be more specific for the refrigerated products, the partial
      replacement of milk fat by these ingredients may also help, as it improves the
      nutritional value of mousses in both storage conditions.

PMID- 20056290
TI  - C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid
      amide hydrolase (FAAH) and insulin resistance in patients with diabetes mellitus
      type 2.
AB  - BACKGROUND: The polymorphism 385 C/A of FAAH has been associated with overweight
      and obesity. The aim of our study was to investigate the relationship of
      polymorphism (cDNA 385 C-->A) of FAAH gene on obesity parameters in patients with
      diabetes mellitus type 2. DESIGN: A population of 70 patients with diabetes
      mellitus type 2 was analyzed. An anthropometric and biochemical nutritional
      assessment was performed. The statistical analysis was performed for the combined
      C358A and A358A as a group and wild type C358C as second group. RESULTS: Fifty
      five patients (78.7%) had genotype C358C (wild type group) and 15 (21.3%)
      patients C358A (14 patients, 20.6%) or A358A (1 patient, 0.7%) (mutant group).
      BMI (38.9+/-6.4 vs. 39.2+/-5.7, p<0.05), weight (96.8+/-17.6kg vs. 102.5+/
      16.8kg, p<0.05), fat mass (42.1+/-16.1kg. vs. 46.9+/-11.1kg, p<0.05), waist
      circumference (115.9+/-12.8cm vs. 121.3+/-12.8cm, p<0.05), insulin (22.5+/
      18.8mUI/L vs. 33.9+/-17.1UI/L, p<0.05) and TNF-alpha (6.1+/-3.4pg/mL vs. 8.4+/
      3.2pg/mL, p<0.05) were higher in mutant type group than wild type. Adiponectin
      levels (33.3+/-20.8ng/mL vs. 22.3+/-10.8ng/mL, p<0.05) were higher in wild type
      group than mutant type group. CONCLUSION: There is an association of the mutant
      type group A358C and A358A of FAAH with a worse cardiovascular profile (weight,
      body mass index, waist circumference, insulin,TNF-alpha and adiponectin levels)
      than wild type group.

PMID- 20056291
TI  - The replication cycle of hepatitis B virus.

PMID- 20056292
TI  - Impact of regulation of Community Pharmacies on efficiency, access and equity.
      Evidence from the UK and Spain.
AB  - In this paper, we focus on regulatory restrictions on Community Pharmacies and
      whether these have an impact on efficiency, access and equity and thus in the
      delivery of services community pharmacists provide to patients. Primary data
      collection through semi-structured interviews and secondary data collection
      through literature review have been used with a particular focus on Spain (a
      country where Community Pharmacy is strictly regulated) and the UK (a country
      where Community Pharmacy is considered liberalised by EU standards). The findings
      indicate that improved pharmacy operational efficiency is the result of
      appropriate incentive structures, ownership liberalisation and OTC price freedom
      as is the case in the UK. Equity and access seem to be better achieved by
      establishing geographic, demographic or needs-based criteria to open new
      pharmacies (as is the case in Spain). In sum, there are useful lessons for both
      countries: the UK could look into the policies applied in Spain that increase
      access and equity whilst Spain could adopt some of the policies from the UK to
      increase efficiency in the system.

PMID- 20056293
TI  - Mutation of the chitinase-like protein-encoding AtCTL2 gene enhances lignin
      accumulation in dark-grown Arabidopsis seedlings.
AB  - Several genes that encode a chitinase-like protein (called the CTL group) have
      been identified in Arabidopsis, rice, pea, and cotton. Members of the CTL group
      have attracted much attention because of their possible role in the biosynthesis
      of the cell wall in plants. The hot2 mutation in the CTL1 (AtCTL1) gene of
      Arabidopsis thaliana causes multiple defects in growth and development. The
      Arabidopsis genome possesses the AtCTL2 gene, which exhibits 70% similarity to
      AtCTL1 at the amino acid level. We showed that the AtCTL2 gene was predominantly
      expressed in stems, which was in contrast to the presence of AtCTL1 transcripts
      in most organs of Arabidopsis. In addition, beta-glucuronidase (GUS) staining was
      detectable in all tissues of the stem in transgenic plants expressing the
      AtCTL1::GUS construct, while GUS activity under control of the AtCTL2 promoter
      was significantly restricted to the xylem and to interfascicular fibers in stems.
      The phenotypes of atctl2 single mutant and of hot2, atctl2 double mutant plants
      were significantly similar to those of wild-type and of hot2 single mutant
      plants, respectively. The expression levels of CESA1 and CESA4 transcripts were
      not affected in the two single mutants or corresponding double mutant plants,
      compared with the levels in wild-type plants. The accumulation of lignin in
      etiolated hypocotyls, however, was increased by mutation of AtCTL2. These
      findings suggest that AtCTL2 is required for proper cell wall biosynthesis in
      etiolated seedlings of Arabidopsis.

PMID- 20056294
TI  - [Polar and non polar notations of refraction].
AB  - Refraction can be expressed by four polar notations which correspond to four
      different combinations of spherical or cylindrical lenses. Conventional
      expressions of refraction (plus and minus cylinder notation) are described by
      sphere, cylinder, and axis. In the plus cylinder notation, the axis visualizes
      the most powerful meridian. The axis usually corresponds to the bow tie axis in
      curvature maps. Plus cylinder notation is also valuable for all relaxing
      procedures (i.e., selective suture ablation, arcuate keratotomy, etc.). In the
      cross-cylinder notation, two orthogonal cylinders can describe (without the
      sphere component) the actual refraction of both the principal meridians. This
      notation must be made before performing the vertex calculation. Using an
      association of a Jackson cross-cylinder and a spherical equivalent, refraction
      can be broken down into two pure components: astigmatism and sphere. All polar
      notations of refraction may perfectly characterize a single refraction but are
      not suitable for statistical analysis, which requires nonpolar expression. After
      doubling the axis, a rectangular projection breaks down the Jackson cross
      cylinder, which has a polar axis, into two Jackson cross-cylinders on the 0
      degrees /90 degrees and 45 degrees /135 degrees axis. This procedure results in
      the loss of the directional nature of the data. Refraction can be written in a
      nonpolar notation by three rectangular coordinates (x,y,z), which can also
      represent the spherocylinder by one point in a dioptric space. These three
      independent (orthogonal) variables have a concrete optical significance: a
      spherical component, a direct/inverse (WTR/ATR) component, and an oblique
      component of the astigmatism. Finally, nonpolar notations are useful for
      statistical analysis and graphical representation of refraction.

PMID- 20056295
TI  - [First North African observation of Leber congenital amaurosis secondary to
      CEP290 gene mutation].
AB  - Leber congenital amaurosis (LCA) is a the earliest and most severe form of
      retinal dystrophy responsible for congenital blindness. LCA has genetic
      heterogeneity and the study of this disease is elucidating the genetics and
      molecular interactions involved in the development of the retina. To date, 11 LCA
      genes have been mapped, ten of which have been identified. The CEP290 gene has
      been shown to account for Joubert and Senior-Loken syndromes and to be a frequent
      cause of nonsyndromic LCA. We report here the first Arab patient, born to
      consanguineous parents, with Leber congenital amaurosis attributable to mutation
      of the CEP290 gene.

PMID- 20056296
TI  - [Phacoemulsification: advantages of a consultation the day after surgery?].
AB  - INTRODUCTION: Cataract surgery is the most frequent surgery in France. The D1
      consultation limits the extension of ambulatory care to patients who can return
      on their own the day after sugery. We assessed the usefulness of this systematic
      D1 consultation in terms of therapeutic modifications. MATERIAL AND MeTHODE:
      Retrospective study of patients who underwent cataract surgery in a teaching
      hospital from february to july 2006. The major parameter was the modification of
      postsurgical treatment after the D1 consultation. RESULTS: Of the 380 operated
      eyes studied, the patients included 145 men and 235 women, the mean age was 73.8
      years (range, 43-92), 86% underwent conventional hospitalization, 70% had been
      operated by a senior surgeon, and 66% had no suture. At the D1 visit, 11
      modifications (2.9%) were recorded: one case of athalamia, one Seidel-positive
      test, four cases of high IOP (>30mmHg), and five severe inflammations of the
      anterior segment. All the treatment changes were reported in the group of
      hospitalized patients, none were reported in the ambulatory patients. Of the 380
      eyes studied, only one required sutures at D1, the other treatment changes were
      minor. CONCLUSIONS: The low output of the D1 visit raises the problem of its
      relevance in terms of public health. In most of the English-speaking and
      Scandinavian countries, patients have only one postoperative visit at 1 month.
      Patients could receive written and oral recommendations and a hotline number to
      contact the surgical team, which could allow the D1 visit to be discontinued for
      standard patients with uncomplicated surgery.

PMID- 20056297
TI  - [Macro-CK type 1 and inclusion body myositis].

PMID- 20056298
TI  - Student nurse absenteeism in higher education: An argument against enforced
      attendance.
AB  - Unauthorised student nurse absenteeism in higher education troubles many
      university lecturers. Anecdotally, absenteeism is occasionally raised as an issue
      by attending students who resent others "getting away" with non-attendance and
      some policy documents appear to suggest that attendance should be mandated. This
      paper argues against enforced attendance in higher education and challenges those
      who would mandate attendance to explain and justify their position. Drawing on a
      range of nursing and non-nursing material we here discuss some of the literature
      on attendance, absenteeism, effort or time spent in study and grade attainment.
      Informed by this admittedly partial review we maintain that the evidence linking
      grade attainment with attendance and study effort is less conclusive than
      intuition might initially suggest. We note that enforcing attendance apparently
      runs counter to important pedagogic (humanistic and androgogic) principles. We
      propose that responses to absenteeism cannot be separated from questions of
      'harm' and we suggest that lecturers should refrain from associating non
      attendance with unprofessional behaviour and poor professionalization.

PMID- 20056299
TI  - Delivering high quality midwifery care: the priorities, opportunities and
      challenges for midwives (DH 28/9/09).

PMID- 20056300
TI  - Current therapeutic approaches to fungal infections in immunocompromised
      hematological patients.
AB  - Invasive fungal infections are significant causes of morbidity and mortality in
      patients with hematological malignancies. Patients with acute myeloid leukemia
      and those who have undergone allogeneic hematopoietic stem cell transplantation
      are at especially high risk. Various fungal agents are responsible for this
      complication, but Aspergillus spp. and Candida spp. are the most frequently
      isolated micro-organisms; less commonly, infections could be caused by
      Zygomycetes or other rare molds or yeasts. Several new systemically-administered
      antifungal agents have been approved for clinical use since 2001; these agents
      include liposomal amphotericin B, voriconazole, caspofungin, and posaconazole,
      and they represent a major advance in antifungal therapy and have improved the
      prognosis of patients with hematological malignancies. This review focuses on
      therapeutic aspects of the management of fungal infections in hematological
      patients.

PMID- 20056301
TI  - Plasticity in physiological traits in conifers: implications for response to
      climate change in the western U.S.
AB  - Population variation in ecophysiological traits of four co-occurring montane
      conifers was measured on a large latitudinal gradient to quantitatively assess
      their potential for response to environmental change. White fir (Abies concolor)
      had the highest variability, gross photosynthetic rate (Pg), and foliar carbon
      (C) and nitrogen (N) content. Despite low water use efficiency (WUE), stomatal
      conductance (gs) of fir was the most responsive to unfavorable environmental
      conditions. Pinus lambertiana exhibited the least variability in Pg and WUE, and
      is likely to be the most vulnerable to environmental changes. Pinus ponderosa had
      an intermediate level of variability, and high needle growth at its higher
      elevational limits. Pinus Jeffreyi also had intermediate variability, but high
      needle growth at its southern latitudinal and lower elevational limits. The
      attributes used to assess tree vigor were effective in predicting population
      vulnerability to abiotic (drought) and biotic (herbivore) stresses.

PMID- 20056302
TI  - An adsorption diffusion model for removal of para-chlorophenol by activated
      carbon derived from bituminous coal.
AB  - Batch adsorption experiments were carried out to study the adsorptive removal and
      diffusion mechanism of para-chlorophenol (p-CP) onto Calgon Filtrasorb 400 (F400)
      activated carbon. The external mass transfer resistance is negligible in the
      adsorption process carried out under different conditions in batch operation.
      Intraparticle diffusion model plots were used to correlate the batch p-CP
      adsorption data; three distinct linear sections were obtained for every batch
      operation. The textural properties of F400 activated carbon showed that it has a
      large portion of supermicropores, which is comparable to the size of the p-CP
      molecules. Due to the stronger interactions between p-CP molecules and F400
      micropores, p-CP molecules predominantly diffused and occupied active sites in
      micropore region by hopping mechanism, and eventually followed by a slow filling
      of mesopores and micropores. This hypothesis is proven by the excellent agreement
      of the intraparticle diffusion model plots and the textural properties of F400
      activated carbon.

PMID- 20056303
TI  - PTSD and its treatment in people with intellectual disabilities: a review of the
      literature.
AB  - Although there is evidence to suggest that people with intellectual disabilities
      (ID) are likely to suffer from Post-Traumatic Stress Disorder (PTSD), reviews of
      the evidence base, and the potential consequences of this contention are absent.
      The purpose of this article is to present a comprehensive account of the
      literature on prevalence, assessment, and treatment of PTSD in people with ID.
      Some support was found for the notion that people with ID have a predisposition
      to the development of PTSD. Differences in comparison with the general population
      may consist of the expression of symptoms, and the interpretation of distressing
      experiences, as the manifestation of possible PTSD seems to vary with the level
      of ID. Since reliable and valid instruments for assessing PTSD in this population
      are completely lacking, there are no prevalence data on PTSD among people with
      ID. Nine articles involve treatment of PTSD in people with ID. Interventions
      reported involve those aimed to establish environmental change, the use of
      medication and psychological treatments (i.e., cognitive behavioral therapy, EMDR
      and psychodynamic based treatments). Case reports suggest positive treatment
      effects for various treatment methods. Development of diagnostic instruments for
      assessment of PTSD symptomatology in this population is required, as it could
      facilitate further research on its prevalence and treatment.

PMID- 20056304
TI  - Network resilience in the face of health system reform.
AB  - Many health systems now use networks as governance structures. Network
      'macroculture' is the complex of artefacts, espoused values and unarticulated
      assumptions through which network members coordinate network activities.
      Knowledge of how network macroculture during 2006-2008 develops is therefore of
      value for understanding how health networks operate, how health system reforms
      affect them, and how networks function (and can be used) as governance
      structures. To examine how quasi-market reforms impact upon health networks'
      macrocultures we systematically compared longitudinal case studies of these
      impacts across two care networks, a programme network and a user-experience
      network in the English NHS. We conducted interviews with key informants, focus
      groups, non-participant observations of meetings and analyses of key documents.
      We found that in these networks, artefacts adapted to health system reform faster
      than espoused values did, and the latter adapted faster than basic underlying
      assumptions. These findings contribute to knowledge by providing empirical
      support for theories which hold that changes in networks' core practical activity
      are what stimulate changes in other aspects of network macroculture. The most
      powerful way of using network macroculture to manage the formation and operation
      of health networks therefore appears to be by focusing managerial activity on the
      ways in which networks produce their core artefacts.

PMID- 20056306
TI  - Sinistrals' upper hand: evidence for handedness differences in the representation
      of body space.
AB  - A difference in the perception of extrapersonal space has been shown to exist
      between dextrals and sinistrals. On the classical line bisection task, this
      difference is evident in a greater left bias for dextrals compared to sinistrals.
      Different modalities and regions of space can be affected. However, it has not
      yet been investigated whether a systematic bias also exists for the perception of
      personal or body space. We investigated this by using three tasks which assess
      different aspects of personal space in an implicit and explicit way. These tasks
      were performed by strongly right-handed (dextrals), strongly left-handed
      (sinistrals) and mixed-handed participants. First, a task of pointing to three
      areas of one's own body without the use of visual information showed dextrals to
      have an asymmetric estimation of their body. In right hemispace, dextrals'
      pointing was at a greater distance from the midsagittal plane compared to
      pointing in left hemispace. No such asymmetry was present for sinistrals, while
      mixed-handers' performance was intermediate to that of strong right- and strong
      left-handers. Second, a task of recovering circular patches from their body
      surface whilst blindfolded also showed superior performance of sinistrals
      compared to dextrals. On these two tasks, there was also a moderate relationship
      between handedness scores and performance measures. Third, a computer-based task
      of adjusting scaled body-outline-halves showed no handedness differences.
      Overall, these findings suggest handedness differences in the implicit but not
      explicit representation of one's own body space. Possible mechanisms underlying
      the handedness differences shown for the implicit tasks are a stronger
      lateralization or a greater activation imbalance for dextrals and/or greater
      access to right hemispheric functions, such as an "up-to-date body"
      representation, by sinistrals. In contrast, explicit measures of how body space
      is represented may not be affected due to their relying on a different processing
      pathway.

PMID- 20056305
TI  - Osteonecrosis of the jawbones in 2 osteoporosis patients treated with nitrogen
      containing bisphosphonates: osteonecrosis reduction replacing NBP with non-NBP
      (etidronate) and rationale.

PMID- 20056308
TI  - Maternal polycystic ovary syndrome may be associated with adverse pregnancy
      outcomes.
AB  - OBJECTIVE: To determine whether maternal polycystic ovary syndrome (PCOS) is
      associated with adverse pregnancy outcomes in a population of Italian
      parturients. STUDY DESIGN: Retrospective study carried out in an academic
      hospital in Bologna, Italy, including 516 consecutive Italian women who delivered
      between January and April 2006. PCOS women, women with hyperandrogenic features
      not configuring PCOS (Intermediate group) and non-hyperandrogenic controls were
      identified by a telephone survey of 229 women. Statistical analysis was performed
      using ANOVA or chi-square. RESULTS: PCOS women, accounted for 6.6% of our cohort.
      Gestational diabetes mellitus (GDM) was significantly more frequent in the PCOS
      group than in the other groups (20% vs. 3.6% and 4%; P<0.01). The association of
      GDM and pregnancy-induced hypertension occurred in one subject in the PCOS group
      but in none of the other groups (P<0.001). Preterm birth was more frequent in the
      PCOS group than in control group (20% vs. 6.9%; P<0.05), whereas mean length of
      gestation was not different. The higher occurrence of adverse outcomes may be, at
      least partly, related to a higher weight gain during pregnancy in PCOS group with
      respect to the other groups (P<0.05). CONCLUSIONS: Women affected by PCOS carry
      an increased risk of adverse pregnancy outcomes.

PMID- 20056307
TI  - The utility of sputum eosinophils and exhaled nitric oxide for monitoring asthma
      control with special attention to childhood asthma.
AB  - The monitoring of sputum eosinophils has received certain attention as a tool for
      improving asthma management both in children and in adults. The present paper
      reviews the technique and also the usefulness of induced sputum in the diagnosis
      and assessment of asthma, together with its ability to predict the response to
      treatment and to anticipate asthma exacerbations. Special attention is addressed
      to childhood asthma. The authors conclude that due to cost-effectiveness reasons
      derived from high labour costs, together with the unpleasantness of the technique
      and the failure to obtain adequate samples in a non-negligible percentage of
      children, this technique should be only used for research purposes.

PMID- 20056309
TI  - Betamethasone before elective caesarean section at term: a survey of practice in
      France.

PMID- 20056310
TI  - Regeneration of acinar cells following ligation of rat submandibular gland
      retraces the embryonic-perinatal pathway of cytodifferentiation.
AB  - Rat submandibular gland can regenerate following ligation-induced atrophy,
      eventually recovering its normal morphology and function. Previous studies have
      suggested that the regeneration process implies both self-proliferation of
      existing acini and formation of new acinar cells. One hypothesis is that new
      acinar cells may differentiate from the ductal cells in a similar fashion to the
      process of cytodifferentiation occurring during submandibular glandular
      development. In this study atrophy was induced, under recovery anaesthesia, by
      applying a metal clip on the main duct of the submandibular gland without
      including the chorda lingual nerve. After 2 weeks the duct was deligated for 3, 5
      or 7 days or 8 weeks and the glands collected. Tissue was prepared for
      immunohistochemistry, biochemical analysis and RNA extraction. The histology of
      the regenerated glands shows several normal-looking acini, which have regained
      their glycoprotein content (AB/PAS positive), data also confirmed by biochemical
      analysis (SDS-PAGE/PAS). Regenerating tissue was characterized by the presence of
      embryonic-like branched structures ending with AB/PAS positive acinar cells. The
      proteins SMG-B and PSP are normally expressed in acinar cell precursors during
      development but only by intercalated ductal cells in the adult stage. In the
      adult regenerating gland mRNA levels of both SMG-B and PSP were found to be up
      regulated compared to ligated glands and SMG-B expression localized to acinar
      cells whilst the ductal cells were negative. This study of rat submandibular
      gland regeneration suggests new acinar cells have differentiated from ducts and
      express markers of acinar cell precursors in a similar manner to the
      cytodifferentiation process occurring during glandular development.

PMID- 20056311
TI  - Posterior pusher syndrome: A report of two cases.
AB  - "Pusher syndrome" is classically described as a disorder of body orientation in
      the coronal plane. Although it mainly occurs in stroke patients, non-stroke
      causes have been described. Pusher behaviour is characterized by a tilt towards
      the contralesional paretic side and a resistance to external attempts to rectify.
      It may occur with or without hemispatial neglect, which in itself may be the
      cause of a usually ipsilesional shift of attention and body orientation in the
      axial plane. In this report we describe two patients with a marked disturbance of
      body orientation in the sagittal plane with imbalance, posterior tilt and an
      active resistance to forward pulling or pushing. By analogy we propose the term
      "posterior pusher" syndrome for the clinical picture.

PMID- 20056312
TI  - Management of meningiomas.
AB  - The primary treatment of meningiomas is surgery which can be curative if the
      tumor is completely removed. For parasagittal, lateral sphenoid wing and
      olfactory groove meningiomas, gross-total resection should be the goal.
      Tuberculum and diaphragma sella meningiomas can be resected through the
      subfrontal or the pterional approaches. In meningiomas of the sphenoid wing with
      osseous involvement or involvement of the cavernous sinus subtotal resection can
      be achieved via several surgical approaches. Similarly, subtotal resection rather
      than gross-total resection of meningiomas of the petroclival, parasellar, and
      posterior fossa regions can preserve neurological function. Prior to surgery,
      embolization may reduce intraoperative bleeding and prevent postoperative
      complications. Stereotactic radiosurgery can be used as an alternative treatment
      to surgery either as a first-line treatment or at recurrence. Various
      conventional radiotherapy techniques can be employed for residual tumor post
      surgery or at recurrence. Chemotherapy has modest activity and is reserved for
      selected cases.

PMID- 20056313
TI  - Spinal intradural haemorrhage in a patient with Wegener's Granulomatosis.
AB  - We describe the case of a patient with known Wegener's Granulomatosis who
      developed a spontaneous intradural haematoma in the thoracic spine against a
      background of a recent relapse in her vasculitis. Decompression resulted in a
      rapid recovery of lower limb function. We propose involvement of the spinal
      meninges in the systemic vasculitis as the cause of haemorrhage.

PMID- 20056314
TI  - Tephrosin induces internalization and degradation of EGFR and ErbB2 in HT-29
      human colon cancer cells.
AB  - Inactivation of epidermal growth factor receptor (EGFR) family members are prime
      targets for cancer therapy. Here, we show that tephrosin, a natural rotenoid
      which has potent antitumor activities, induced internalization of EGFR and ErbB2,
      and thereby induced degradation of the receptors. Treatment of HT-29 cells with
      tephrosin inhibited both the ligand-induced and constitutive phosphorylation of
      EGFR, ErbB2 and ErbB3, and concomitantly suppressed the activation of the
      downstream signaling molecules such as Akt and Erk1/2 mitogen-activated protein
      kinase (MAPK). Tephrosin caused internalization of EGFR and ErbB2 into vehicles,
      which resulted in degradation of the receptors. This degradation was blocked by
      the lysosomal inhibitor, chloroquine. We also showed that tephrosin induced
      apoptosis. Tephrosin did not induce the proteolytic processing of caspase-3 and
      poly(ADP-ribose) polymerase (PARP), but did nuclear translocation of apoptosis
      inducing factor (AIF), suggesting that tephrosin may induce caspase-independent
      apoptosis. These findings provide the first evidence that tephrosin could exert
      antitumor effects by inducing internalization and degradation of inactivated EGFR
      and ErbB2 in human colon cancer cells.

PMID- 20056315
TI  - Biomarkers for predicting the sensitivity of cancer cells to TRAIL-R1 agonistic
      monoclonal antibody.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and an agonistic
      monoclonal antibody to TRAIL-R1 (TRAIL-R1 mAb) induce apoptosis and show anti
      proliferative activity in vitro and in vivo. However, some TRAIL-R1-expressing
      cell lines are not sensitive to either TRAIL-R1 mAb or TRAIL. We have identified
      four genes (STK17B, SP140L, CASP8, and AIM1) whose expression levels differ
      significantly between TRAIL-R1 mAb-sensitive and resistant cell lines. Using the
      expression levels of these genes, we predicted TRAIL-R1 mAb and TRAIL sensitivity
      in our test cell lines with 75% (9/12) and 84% (21/25) accuracy, respectively.
      Knockdown of STK17B in TRAIL-R1 mAb-sensitive cells augmented Bcl-2 expression
      and suppressed TRAIL-R1 mAb-induced apoptosis. Our results may be useful for
      predicting the response of cancers to TRAIL-agonistic drugs in the clinic.

PMID- 20056316
TI  - Characterization of a humanized anti-CD20 antibody with potent antitumor activity
      against B-cell lymphoma.
AB  - Despite the effectiveness of the anti-CD20 chimeric antibody (mAb), rituximab, in
      treating B-cell lymphomas, its efficacy remains variable and often modest. In
      this study, a humanized anti-CD20 antibody, hu8E4, was generated by
      complementarity-determining region grafting method. Hu8E4 was as effective as
      rituximab in mediating antibody-dependent cellular cytotoxicity and inducing
      apoptosis in B-lymphoma cells, but it exhibited much more potent complement
      dependent cytotoxicity than rituximab. Immunotherapeutic studies showed that
      hu8E4 was significantly more effective than rituximab in prolonging the survival
      of severe combined immunodeficient mice bearing human B-cell lymphomas,
      suggesting that it might be a promising therapeutic agent for B-cell lymphomas.

PMID- 20056317
TI  - Rapid determination of the toxicity of quantum dots with luminous bacteria.
AB  - In this paper, a novel method so-called bioluminescence inhibition assay with
      luminous bacteria (Photobacterium phosphoreum) was introduced to evaluate the
      toxicity of quantum dots. The bioassay was based on measuring the decrease of the
      light emitted by luminous bacteria. With obvious advantages of simplicity,
      rapidity and sensitivity, it can dramatically improve the efficiency of probing
      the toxicity of QDs. Based on this method, we systemically explored the effect of
      the composition and surface modification on QDs' toxicity. The experiment of
      composition effect was performed using three kinds of QDs, namely CdSe, CdTe and
      ZnS-AgInS(2) QDs with the same stabilizer - dihydrolipoic acid. As for the effect
      of different stabilizers, mercaptoacetic acid, l-cysteine and dihydrolipoic acid
      stabilized CdSe were researched, respectively. Our results demonstrated that both
      the composition and surface modification were the important factors affecting the
      toxicity of QDs. In addition, a concentration dependence of toxicity was also
      found.

PMID- 20056318
TI  - Human health and ecological toxicity potentials due to heavy metal content in
      waste electronic devices with flat panel displays.
AB  - Display devices such as cathode-ray tube (CRT) televisions and computer monitors
      are known to contain toxic substances and have consequently been banned from
      disposal in landfills in the State of California and elsewhere. New types of flat
      panel display (FPD) devices, millions of which are now purchased each year, also
      contain toxic substances, but have not previously been systematically studied and
      compared to assess the potential impact that could result from their ultimate
      disposal. In the current work, the focus is on the evaluation of end-of-life
      toxicity potential from the heavy metal content in select FPD devices with the
      intent to inform material selection and design-for-environment (DfE) decisions.
      Specifically, the metals antimony, arsenic, barium, beryllium, cadmium, chromium,
      cobalt, copper, lead, mercury, molybdenum, nickel, selenium, silver, vanadium,
      and zinc in plasma TVs, LCD (liquid crystal display) TVs, LCD computer monitors
      and laptop computers are considered. The human health and ecotoxicity potentials
      are evaluated through a life cycle assessment perspective by combining data on
      the respective heavy metal contents, the characterization factors in the U.S. EPA
      Tool for the Reduction and Assessment of Chemical and other environmental Impacts
      (TRACI), and a pathway and impact model. Principal contributors to the toxicity
      potentials are lead, arsenic, copper, and mercury. Although the heavy metal
      content in newer flat panel display devices creates less human health toxicity
      potential than that in CRTs, for ecological toxicity, the new devices are worse,
      especially because of the mercury in LCD TVs and the copper in plasma TVs.

PMID- 20056319
TI  - Isolation and preconcentration of Cd(II) from environmental samples using
      polypropylene porous membrane in a hollow fiber renewal liquid membrane
      extraction procedure and determination by FAAS.
AB  - The use of polypropylene porous membrane in a hollow fiber renewal liquid
      membrane (HFRLM) procedure for determination of Cd(II) in water samples was
      assessed. Ammonium O,O-diethyl dithiophosphate (DDTP) was used to complex cadmium
      (II) in an acid medium to obtain a neutral hydrophobic complex. The organic
      solvent introduced to the sample extracts this complex from the aqueous solution
      and carries it over the polypropylene membrane porous. The organic solvent is
      immobilized inside the polypropylene membrane porous, leading to an homogeneous
      phase. The complex strips the lumen of the membrane where, at higher pH, the
      complex Cd-DDTP is broken down and Cd(II) is released into the stripping phase.
      EDTA was used to complex the cadmium (II), helping to trap the analyte in the
      stripping phase. The optimized variables were: sample pH, DDTP concentration,
      stripping pH, EDTA concentration, extraction temperature and time, extractor
      solvent and addition of salt to saturate the sample. The sample volume used was
      15 mL and the stripping volume was 165 microL. The analyte enrichment factor was
      107, limit of detection 1.5 microg L(-1), relative standard deviation 4.0% (15
      microg L(-1), n=7) and the working linear range 5-30 microg L(-1).

PMID- 20056320
TI  - Effect of dissolved ozone or ferric ions on photodegradation of thiacloprid in
      presence of different TiO2 catalysts.
AB  - Combining TiO(2) photocatalysis with inorganic oxidants (such as O(3) and
      H(2)O(2)) or transition metal ions (Fe(3+), Cu(2+) and Ag(+)) often leads to a
      synergic effect. Electron transfer between TiO(2) and the oxidant is usually
      involved. Accordingly, the degree of synergy could be influenced by TiO(2)
      surface area. With this in mind, the disappearance of thiacloprid, a
      neonicotinoid insecticide, was studied applying various photochemical AOPs and
      different TiO(2) photocatalysts. In photocatalytic ozonation experiments,
      synergic effect of three different TiO(2) photocatalysts was quantified. Higher
      surface area resulted in a more pronounced synergic effect but an increasing
      amount of TiO(2) did not influence the degree of the synergy. This supports the
      theory that the synergy is a consequence of adsorption of ozone on the TiO(2)
      surface. No synergy was observed in photocatalytic degradation of thiacloprid in
      the presence of dissolved iron(III) species performed under varied experimental
      conditions (concentration, age of iron(III) solution, different TiO(2) films,
      usage of TiO(2) slurries). This goes against the literature for different organic
      compounds (i.e., monuron). It indicates different roles of iron(III) in the
      photodegradation of different organic molecules. Moreover, TiO(2) surface area
      did not affect photodegradation efficiency in iron(III)-based experiments which
      could confirm absence of electron transfer between TiO(2) photocatalyst and
      iron(III).

PMID- 20056321
TI  - A review on methods of regeneration of spent pickling solutions from steel
      processing.
AB  - The review presents various techniques of regeneration of spent pickling
      solutions, including the methods with acid recovery, such as diffusion dialysis,
      electrodialysis, membrane electrolysis and membrane distillation, evaporation,
      precipitation and spray roasting as well as those with acid and metal recovery:
      ion exchange, retardation, crystallization solvent and membrane extraction.
      Advantages and disadvantages of the techniques are presented, discussed and
      confronted with the best available techniques requirements. Most of the methods
      presented meet the BAT requirements. The best available techniques are
      electrodialysis, diffusion dialysis and crystallization; however, in practice
      spray roasting and retardation/ion-exchange are applied most frequently for spent
      pickling solution regeneration. As "waiting for their chance" solvent extraction,
      non-dispersive solvent extraction and membrane distillation should be indicated
      because they are well investigated and developed. Environmental and economic
      benefits of the methods presented in the review depend on the cost of chemicals
      and wastewater treatment, legislative regulations and cost of modernization of
      existing technologies or implementation of new ones.

PMID- 20056322
TI  - Efficient removal of dyes in water using chitosan microsphere supported cobalt
      (II) tetrasulfophthalocyanine with H2O2.
AB  - A new efficient catalyst, CoTSPc@chitosan, was developed by immobilizing water
      soluble cobalt (II) tetrasulfophthalocyanine onto adsorbent chitosan microspheres
      covalently for the heterogeneous catalytic oxidation of C. I. Acid Red 73 with
      H(2)O(2). The result indicated that the COD removal and discoloration of C. I.
      Acid Red 73 made 55 and 95% respectively in the presence of CoTSPc@chitosan with
      H(2)O(2) in 4h. In addition, CoTSPc@chitosan-H(2)O(2) system could proceed
      efficiently in a relatively wide pH range and remain high catalytic activity
      after 6 reuse cycles. Furthermore, the adsorption study of CoTSPc@chitosan
      confirmed that chitosan was an outstanding support which contributed a lot to the
      removal reaction. In conclusion, the combination of adsorption process and
      catalytic oxidation made the CoTSPc@chitosan-H(2)O(2) system achieve a simple,
      efficiently and environmentally friendly water treatment.

PMID- 20056323
TI  - Fabrication of a novel iron(III)-PVC membrane sensor based on a new 1,1'
      (iminobis(methan-1-yl-1-ylidene))dinaphthalen-2-ol synthetic ionophore for direct
      and indirect determination of free iron species in some biological and non
      biological samples.
AB  - In this novel, the iron(III)-PVC membrane sensor was investigated based on a new
      1,1'-(iminobis(methan-1-yl-1-ylidene))dinaphthalen-2-ol (IBMYD) synthetic
      ionophore as a suitable carrier. The best performance was observed for the
      membrane composition including 33.0% PVC, 65.0% TEHP, 1.0% NaTPB and 1.0%
      ionophore. The electrode displayed a linear potential response over a wide
      concentration range from 1.0 x 10(-7) to 1.0 x 10(-1)mol L(-1), with a detection
      limit of 5.0 x 10(-8)mol L(-1) and a good Nernstian slope of 19.9+/-0.3 mV
      decade(-1). The sensor possessed some advantages such as short conditioning time,
      very fast response time (<12s) and especially good discriminating ability towards
      Fe(III) ions over a wide variety of alkali, alkaline earth, transition, and heavy
      metal ions. The potential response of the proposed sensor was independent of the
      pH of the test solution, in the pH working range from 3.0 to 6.3. The fabricated
      electrode was applied for at least 2 months, without any measurable divergence in
      the potential characteristics. The optimized sensor was used successfully for
      direct and indirect determination of free iron species in some different
      synthetic and real samples with satisfactory results.

PMID- 20056324
TI  - Bioreduction of trivalent aurum to nano-crystalline gold particles by active and
      inactive cells and cell-free extract of Aspergillus oryzae var. viridis.
AB  - Bioreduction efficacy of both active (AB) and inactive (IB) cells/biomass of
      Aspergillus oryzae var. viridis and their respective cell-free extracts (ACE and
      ICE) to convert trivalent aurum to gold nanoparticles were tested in the present
      study. Strong plasmon resonance of gold nanoparticles was observed between 540
      and 560 nm in the samples obtained from AB, IB, ACE and ICE. Transmission
      electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM),
      energy dispersive X-ray (EDX) and X-ray diffraction (XRD) were performed to
      examine the formation of gold nanoparticles. Comparing all four forms of A.
      oryzae var. viridis, ICE showed high gold nanoparticle productivity. The
      nanoparticles formed were quite uniform in shape and ranged in size from 10 to 60
      nm. In addition some triangle, pentagon and hexagon-shaped nanoplates with size
      range of 30-400 nm were also synthesized especially at lower pH. Organics from
      the inactive cells are believed to be responsible for reduction of trivalent
      aurum to nano-sized gold particles. Organic content of the ICE was found to be
      double the amount of ACE. High productivity of gold nanoparticles by metabolic
      independent process opens up an interesting area of nanoparticle synthesis using
      waste fungal biomass from industries.

PMID- 20056325
TI  - "In situ" phytostabilisation of heavy metal polluted soils using Lupinus luteus
      inoculated with metal resistant plant-growth promoting rhizobacteria.
AB  - The aim of this work is the evaluation of metal phytostabilisation potential of
      Lupinus luteus inoculated with Bradyrhizobium sp. 750 and heavy metal resistant
      PGPRs (plant-growth promoting rhizobacteria), for in situ reclamation of multi
      metal contaminated soil after a mine spill. Yellow lupines accumulated heavy
      metals mainly in roots (Cu, Cd and especially Pb were poorly translocated to
      shoots). This indicates a potential use of this plant in metal
      phytostabilisation. Furthermore, As accumulation was undetectable. On the other
      hand, zinc accumulation was 10-100 times higher than all other metals, both in
      roots and in shoots. Inoculation with Bradyrhizobium sp. 750 increased both
      biomass and nitrogen content, indicating that nitrogen fixation was effective in
      soils with moderate levels of contamination. Co-inoculation of lupines with a
      consortium of metal resistant PGPR (including Bradyrhizobium sp., Pseudomonas sp.
      and Ochrobactrum cytisi) produced an additional improvement of plant biomass. At
      the same time, a decrease in metal accumulation was observed, both in shoots and
      roots, which could be due to a protective effect exerted on plant rhizosphere.
      Our results indicate the usefulness of L. luteus inoculated with a bacterial
      consortium of metal resistant PGPRs as a method for in situ reclamation of metal
      polluted soils.

PMID- 20056327
TI  - Development and evaluation of a nested PCR based on spherical body protein 2 gene
      for the diagnosis of Babesia bovis infection.
AB  - We developed and evaluated a nested PCR assay for the diagnosis of Babesia bovis
      infection in cattle based on the spherical body protein 2 gene (SBP2) from B.
      bovis. The specificity and sensitivity of the test were compared with the B.
      bovis RAP-1 gene nPCR. The SBP2 primers have specificities of 100% for B. bovis
      DNA. The sensitivity of the SBP2 nPCR to B. bovis from the in vitro cultured
      parasites was higher than that of the B. bovis RAP-1 gene nPCR, and a parasitemia
      as low as 10(-8)% was detected. The sensitivity of the SBP2 nPCR to B. bovis
      diluted genomic DNA was also higher than that of B. bovis RAP-1 gene nPCR, and as
      little as 1fg per test detected. For field applications, the sensitivity to a
      total of 145 field samples from Ghana, Mongolia, and Brazil was evaluated. The
      nPCR assay of spherical body protein-2 gene detected 87.6% (127/145), while B.
      bovis RAP-1 gene nPCR detected 37.2% (51/145) of the total samples examined. This
      nPCR assay provides a good diagnostic tool for the laboratory diagnostic
      assessment of B. bovis infection in cattle worldwide.

PMID- 20056328
TI  - Naturally acquired visceral leishmaniasis in non-human primates in Brazil.
AB  - Visceral leishmaniasis (VL) is a chronic and often fatal protozoal disease that
      is endemic in Belo Horizonte (State of Minas Gerais, Brazil). Leishmania sp. is
      an intracellular obligatory parasite of macrophages that can naturally infect
      several mammalian species. Non-human primates (NHP) have been used as
      experimental models for infection with Leishmania of the donovani complex. The
      present report describes a case of visceral leishmaniasis in a black-fronted
      titi. Among 41 primates kept in captivity in a zoo in Belo Horizonte (State of
      Minas Gerais, Brazil), one animal, a black-fronted titi (Callicebus nigrifrons),
      was positive for Leishmania chagasi infection by PCR and immunohistochemistry,
      and developed a fatal disease with clinical signs and lesions compatible with VL.
      Other 17 NHP, including six black-fronted titis (C. nigrifrons), one howler
      monkey (Alouatta guariba), three golden-bellied capuchins (Cebus xanthosternos),
      one golden-headed lion tamarin (Leontopithecus crysomelas), one black-headed owl
      monkey (Aotus nigriceps), two Rio Tapajos sakis (Pithecia irrorata) and three
      emperor tamarins (Saguinus imperator) had blood samples that tested positive for
      amplification of Leishmania kDNA by PCR, although these NPH had no clinical signs
      of the disease.

PMID- 20056329
TI  - Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) resistance to fipronil in
      Uruguay evaluated by in vitro bioassays.
AB  - Rhipicephalus (Boophilus) microplus obtained from four local populations in
      Uruguay (2007-2008) were subjected to various bioassay techniques to determine
      the presence of fipronil resistance within the country. Resistance ratios (RRs)
      obtained by larval immersion test varied between 3.3 and 3635 for tick
      populations subjected to treatment with fipronil for the last 3-7 years. The
      highest RR was observed in the population which received fewer treatments. Using
      discriminating concentration (8ppm) for larval immersion test, all field strains
      were correctly diagnosed as fipronil-resistant. This study presents the first
      diagnoses of cattle tick resistance to fipronil in Uruguay's field populations.
      It also highlights the importance of the possible conflict between programs to
      control agricultural pests and cattle ticks. The findings provide valuable
      information for selection and adoption of new control alternatives to manage drug
      resistance exhibited by cattle ticks.

PMID- 20056330
TI  - A descriptive study of the occurrence and significance of lipids in Taenia
      hydatigena eggs.
AB  - The aim of this work was to investigate the lipid content of Taenia hydatigena
      eggs and to evaluate the role of lipids in the maintenance of embryo viability.
      The total lipid content of the egg was 4.5% (w/w). Five classes of neutral lipids
      were identified: esterified cholesterol, free cholesterol, triacylglycerols,
      diacylglycerols and free fatty acids. Our results suggest that triacylglycerols
      play a key role in the maintenance of embryo viability. In addition, we found
      that T. hydatigena eggs remain metabolically active by mobilisation of stored
      triacylglycerols. This study contributes to the understanding the survival
      strategies of a member of the Taeniidae family in the environment outside the
      host.

PMID- 20056332
TI  - Lungworm infection in small ruminants: prevalence and associated risk factors in
      Dessie and Kombolcha districts, northeastern Ethiopia.
AB  - A cross-sectional study was conducted from November 2008 to March 2009 to
      estimate the prevalence of lungworm infection and to investigate some of the risk
      factors associated with small ruminant lungworm infections in Dessie and
      Kombolcha districts, northeastern Ethiopia. Faecal samples were collected from
      randomly selected 404 animals (240 sheep and 164 goats) to examine first stage
      larvae (L(1)) using modified Baerman technique. One hundred and thirty eight
      animals (113 sheep and 25 goats) were also subjected to postmortem examination to
      detect the presence of adult lungworm parasites. The overall prevalence recorded
      by faecal and postmortem examinations were 36.9% and 62.3%, respectively.
      Prevalence of lungworm infection was significantly higher (OR=2.1, 95% CI=1.2,
      3.5) in sheep (40.4%) than in goats (31.7%). The proportions of infection by
      Dictyocaulus filaria (D. filaria), Mullerius capillaris (M. capillaris) and mixed
      infection were 1.3% (3/240), 28.3% (68/240) and 10.8% (26/240) in sheep; and
      20.1% (33/164) by M. capillaris and 11.6% (19/164) with mixed infection in goats.
      Animals above one year (OR=8.7, 95% CI=4.8, 15.6), non-dewormed animals (OR=10.4,
      95% CI=5.6, 19.3) and those sampled during November (OR=3.6, 95% CI=1.5, 8.6) had
      higher odds of infection prevalence than animals in corresponding groups. The
      mean count of L(1) larvae of D. filaria and M. capillaris were 5.4 (95% CI=3.6,
      7.3) and 39.3 (95% CI=33.7, 44.9) in ovine and 4.5 (95% CI=3.1, 5.8) and 34.1
      (95% CI=27.2, 41.1) in caprine, respectively. The recorded average larval count
      of the two parasitic species varied significantly in both sheep and goats. This
      study showed high prevalence of lungworm infections which impairs the
      productivity of small ruminants, implying the need for control intervention.

PMID- 20056331
TI  - Quantitation of cytokine mRNA by real-time RT-PCR during a vaccination trial in a
      rabbit model of fascioliasis.
AB  - Use of the rabbit as disease model has long been hampered by a lack of
      immunological assays specific to this species. In the present study we developed
      a SYBR Green-based, real-time RT-PCR protocol to quantitate cytokine mRNA in
      freshly harvested rabbit peripheral mononuclear cells. The method was validated
      in the course of a vaccination trial in which animals vaccinated with the
      recombinant antigen FhSAP2 were challenged with Fasciola hepatica metacercariae.
      Changes in the levels of rabbit interleukin (IL)-2, IL-4, IL-6, IL-10, tumor
      necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) mRNA were
      determined. Messenger RNA from the universally expressed housekeeping gene GAPDH
      was used as an amplification control and allowed for correction of variations in
      the efficiencies of RNA extraction and reverse transcription. Rabbits vaccinated
      with FhSAP2 showed an 83.3% reduction in liver fluke burden after challenge
      infection when compared to non-vaccinated controls. All cytokine mRNAs were found
      at detectable levels; however, the levels of IFNgamma, TNFalpha, IL-2 and IL-10
      were significantly higher in the vaccinated group compared to the non-vaccinated
      group. These results suggest that protection conferred by FhSAP2 protein could be
      associated with a mixed Th1/Th2 immune response in which Th1 cytokines are
      dominant. The real-time RT-PCR method described herein can be a useful tool for
      monitoring changes in basic immune functions in the rabbit model of fascioliasis
      and may also aid in studies of human diseases for which the rabbit is an
      important experimental model.

PMID- 20056333
TI  - Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in
      cancer.
AB  - DNA base excision repair (BER) is critically involved in the processing of DNA
      base damage induced by alkylating agents. Pharmacological inhibition of BER
      (using PARP inhibitors), either alone or in combination with chemotherapy has
      recently shown promise in clinical trials. Human apurinic/apyrimidinic
      endonuclease 1(APE1) is an essential BER protein that is involved in the
      processing of potentially cytotoxic abasic sites that are obligatory
      intermediates in BER. Here we provide a summary of the basic mechanistic role of
      APE1 in DNA repair and redox regulation and highlight preclinical and clinical
      data that confirm APE1 as a valid anticancer drug target. Development of small
      molecule inhibitors of APE1 is an area of intense research and current evidence
      using APE1 inhibitors has demonstrated potentiation of cytotoxicity of alkylating
      agents in preclinical models implying translational applications in cancer
      patients.

PMID- 20056335
TI  - A systematic review of the Diagnostic and Statistical Manual diagnostic criteria
      for nicotine dependence.
AB  - The Diagnostic and Statistical Manual diagnostic criteria for nicotine dependence
      (DSM-ND) are based on the proposition that dependence is a syndrome that can be
      diagnosed only when a minimum of 3 of the 7 proscribed features are present. The
      DSM-ND criteria are an accepted research measure, but the validity of these
      criteria has not been subjected to a systematic evaluation. To systematically
      review evidence of validity and reliability for the DSM-ND criteria, a literature
      search was conducted of 16 national and international databases. Each article
      with original data was independently reviewed by two or more reviewers. In total,
      380 potentially relevant articles were examined and 169 were reviewed in depth.
      The DSM-ND criteria have seen wide use in research settings, but sensitivity and
      specificity are well below the accepted standards for clinical applications.
      Predictive validity is generally poor. The 7 DSM-ND criteria are regarded as
      having face validity, but no data support a 3-symptom ND diagnostic threshold, or
      a 4-symptom withdrawal syndrome threshold. The DSM incorrectly states that daily
      smoking is a prerequisite for withdrawal symptoms. The DSM shows poor to modest
      concurrence with all other measures of nicotine dependence, smoking behaviors and
      biological measures of tobacco use. The data support the DSM-ND criteria as a
      valid measure of nicotine dependence severity for research applications. However,
      the data do not support the central premise of a 3-symptom diagnostic threshold,
      and no data establish that the DSM-ND criteria provide an accurate diagnosis of
      nicotine dependence.

PMID- 20056336
TI  - Benign joint hypermobility syndrome: a cause of childhood asthma?
AB  - Benign joint hypermobility syndrome (BJHS) is a hereditable disorder of
      connective tissue, which is characterized by the occurrence of multiple
      musculoskeletal problems in hypermobile individuals who do not have a systemic
      rheumatological disease. Rectal, uterine and mitral prolapses, varicose veins,
      myopia and recurrent urinary tract infections are more common in patients with
      BJHS, which indicates a diffuse anomaly in the structure of connective tissue
      rather than a limited involvement of the musculoskeletal system. Asthma, as a
      complex trait disease, develops after environmental exposure to innocuous
      allergens, infectious agents and air pollutants in susceptible individuals on the
      basis of their genetics. However, genetic factors cannot explain the recent rise
      in the prevalence, morbidity, or mortality of asthma. Asthma may also be caused
      by a connective tissue defect. Changes in the mechanical properties of the
      bronchial airways and lung parenchyma may underlie the increased tendency of the
      airways to collapse in asthmatic children. In this paper, we postulate that BJHS
      may lead to persistent childhood wheezing by causing airway collapse through a
      connective tissue defect that affects the structure of the airways.

PMID- 20056334
TI  - Exploiting cellular pathways to develop new treatment strategies for AML.
AB  - The standard approaches to the treatment of acute myeloid leukemia (AML) have
      been predominantly based on cytarabine and anthracyclines. Yet, the outcomes
      associated with AML continue to be poor, especially for those patients who are
      older or carry higher-risk disease. In recent years, extensive research has led
      to the development and study of novel agents which target AML by diverse and
      varied mechanisms. Among these are targeted therapeutics such as kinase
      inhibitors and oligonucleotide constructs. These aim to suppress the production
      or activity of proteins, such as FLT3 and BCL2, among others, and thus disrupt
      related signaling cascades essential for leukemogenesis and proliferation. In
      addition, other agents like flavopiridol appear to target the myeloid blast by
      various mechanisms including suppression of cyclin-dependent kinases and
      interference with nucleotide synthesis. Another class of novel therapies includes
      inhibitors of histone deacetylase, which cause growth arrest and apoptosis
      through histone acetylation and resultant conformational changes. Clinical trials
      are now studying these and other agents alone and in combination with traditional
      cytotoxic therapies, with some encouraging results. In this review, we aim to
      provide a summary of the preclinical and clinical investigations of selected
      promising agents currently under study.

PMID- 20056337
TI  - Alzheimer's disease: cerebral glaucoma?
AB  - In a 1994 Medical Hypotheses paper, it was speculated that high intracranial
      pressure (ICP) might increase the probability of developing Alzheimer's disease
      (AD). A study of cerebrospinal fluid pressure (CSFP) in normal volunteers showed
      interindividual variations in CSFP. Some normals had what would normally be
      considered elevated CSFP. The hypothesis postulated that this subgroup with a
      high characteristic individual ICP level might be more susceptible to developing
      AD. The Medical Hypotheses paper further speculated that in more advanced stages
      of AD, such pressure factor could already be missing due to the disease process.
      The present article discusses recent research findings regarding CSFP
      distribution in AD patients that could be interpreted as support for this
      hypothesis. Exposure of central nervous system tissue to high pressure stress is
      not unique to the ICP space. Indeed, a similar situation occurs in the
      intraocular pressure (IOP) space in eyes with glaucoma. Interestingly, recent
      research has revealed similarities in the process leading to retinal ganglion
      cell death in glaucoma and neuronal cell death in AD. In the present paper, we
      raise the question of whether AD could be a cerebral form of glaucoma. Indeed,
      the linking of glaucoma to mechanisms of AD could reflect the anatomical and
      functional similarities between the IOP space and the ICP space. Further studies
      are warranted, however, especially to determine the possible role of high ICP in
      at least some cases of AD.

PMID- 20056338
TI  - Is the pharynx a muscular hydrostat?
AB  - Failure to maintain the patency of the pharyngeal airway during sleep is central
      to the pathogenesis of obstructive sleep apnoea (OSA). This failure is
      hypothesised to be due to the combination of a small pharyngeal airway and
      inadequate state-dependent neuro-mechanical control. Little is known of how the
      pharyngeal muscles function in an integrated function to alter the size and shape
      of the pharyngeal airway. We hypothesise that the muscles of the pharynx function
      as a muscular hydrostat. Muscular hydrostats are organs that are composed almost
      entirely of muscle, with a complex muscular arrangement within the organ.
      Examples of muscular hydrostats include the mammalian tongue, octopus tentacles,
      elephant trunks and the medicinal leech. During muscle contraction the organ will
      maintain a constant volume as muscle tissue is mostly water and hence
      incompressible. The mechanical effect of contraction of individual muscles within
      the muscular hydrostat is dependent on the integrated activity of all other
      muscles, as muscle orientation is dependent on the organ shape. Functionally the
      significance of the muscular hydrostat model lies in the concept that alterations
      in organ shape are achieved via muscle contraction driven redistribution of
      hydrostatic tissue pressure. The tissues which comprise the pharynx are
      predominantly muscle, and thus incompressible. The pharynx is composed of 20
      muscles that are arranged in a complex fashion. Within the peri-pharyngeal
      tissues the only bony structure is the hyoid bone and in adult humans this is a
      free-floating bone. Evidence already exists that the functional outcome of
      contraction of some of the pharyngeal muscles is dependent on stage of
      respiration, the intra-luminal pressure, or the position of the hyoid bone when
      the muscle is activated. There is also evidence that muscle contraction can alter
      the pressure in the tissues surrounding the pharynx in a non-uniform fashion.
      However, it has not been demonstrated for the pharynx that pharyngeal luminal
      shape is determined by muscle contraction determined transmural pressure
      distribution. The consequences of this hypothesis are that reported pharyngeal
      anatomical abnormalities in subjects with OSA, such as increased peri-pharyngeal
      fat deposition or thickening of the lateral pharyngeal walls, could result in
      alteration in integrated muscular function and thus a failure to maintain upper
      airway patency. In addition, nocturnal pharyngeal airway obstruction may result
      from a failure of cross muscle activation. This novel paradigm may lead to
      greater insights into the pathogenesis of OSA as well as opening new avenues for
      exploration of novel therapeutic strategies.

PMID- 20056339
TI  - Oath-taking: a divine prescription for health-related behaviour change?
AB  - Approaches to personal behaviour change include contractual and negotiation
      models. This paper elaborates these partnership models by linking a religious act
      to desired behaviour change beyond narrow and specific domains, such as promotion
      of sexual abstinence. It discusses the hypothesis that oath-taking can facilitate
      positive, health-related behaviour change in human individuals. The change must
      be desired by these individuals when they nevertheless feel conflicted in their
      motives, and believe in a divine presence to which they can oath-take. In support
      of this meta-hypothesis of the effectiveness of oath-taking to a hypothetical
      divinity, we first describe the nature of oaths and oath-taking, including
      legitimacy and satisfaction conditions, and then postulate how ten interrelated
      sets of mechanisms can be expected to facilitate oath-keeping. We playfully and
      heuristically express these mechanisms as 'ten commandments'. Constituting a
      divine prescription for health-related change, the mechanisms require oath-takers
      to: believe in the oath, recognise oath-taking as an established and legitimate
      social behaviour, crystallise the content of the oath, declare the oath aloud,
      oath-take privately if they prefer, commit to relationships that support oath
      taking, replace their relationship with the unwanted behaviour, sanctify the
      divine presence, honour obligations produced by the oath-taking, and fear oath
      breaking. Limitations of oath-taking are then considered as are some of the
      implications of our arguments.

PMID- 20056340
TI  - Positive surgical margins in soft tissue sarcoma treated with preoperative
      radiation: is a postoperative boost necessary?
AB  - PURPOSE: For patients with an extremity soft tissue sarcoma (STS) treated with
      preoperative radiotherapy and surgically excised with positive margins, we
      retrospectively reviewed whether a postoperative radiation boost reduced the risk
      of local recurrence (LR). METHODS AND MATERIALS: A total of 216 patients with
      positive margins after resection of an extremity STS treated between 1986 and
      2003 were identified from our institution's prospectively collected database.
      Patient demographics, radiation therapy parameters including timing and dose,
      classification of positive margin status, reasons for not administering a
      postoperative boost, and oncologic outcome were collected and evaluated. RESULTS:
      Of the 216 patients with a positive surgical margin, 52 patients were treated
      with preoperative radiation therapy alone (50 Gy), whereas 41 received
      preoperative radiation therapy plus a postoperative boost (80% received 16 Gy
      postoperatively for a total of 66 Gy). There was no difference in baseline tumor
      characteristics between the two groups. Six of 52 patients in the group receiving
      preoperative radiation alone developed a LR compared with 9 of 41 in the boost
      group. Five-year estimated LR-free survivals were 90.4% and 73.8%, respectively
      (p = 0.13). CONCLUSIONS: We found that including the postoperative radiation
      boost after preoperative radiation and a margin-positive excision did not provide
      an advantage in preventing LR for patients treated with external beam
      radiotherapy. Given that higher radiation doses placed patients at greater risk
      for late complications such as fracture, fibrosis, edema, and joint stiffness,
      judicious avoidance of the postoperative boost while maintaining an equivalent
      rate of local control can reduce the risk of these difficult-to-treat
      morbidities.

PMID- 20056341
TI  - Fractionated stereotactic radiosurgery for reirradiation of head-and-neck cancer.
AB  - PURPOSE: Stereotactic radiosurgery (SRS) is an appealing treatment option after
      previous radiotherapy because of its precision, conformality, and reduced
      treatment duration. We report our experience with reirradiation using
      fractionated SRS for head-and-neck cancer. METHODS AND MATERIALS: From 2002 to
      2008, 65 patients received SRS to the oropharynx (n = 13), hypopharynx (n = 8),
      nasopharynx (n = 7), paranasal sinus (n = 7), neck (n = 7), and other sites (n =
      23). Thirty-eight patients were treated definitively and 27 patients with
      metastatic disease and/or untreated local disease were treated palliatively. Nine
      patients underwent complete macroscopic resection before SRS. Thirty-three
      patients received concurrent chemoradiation. The median initial radiation dose
      was 67 Gy, and the median reirradiation SRS dose was 30 Gy (21-35 Gy) in 2-5
      fractions. RESULTS: Median follow-up for surviving patients was 16 months. Fifty
      six patients were evaluable for response: 30 (54%) had complete, 15 (27%) had
      partial, and 11 (20%) had no response. Median overall survival (OS) for all
      patients was 12 months. For definitively treated patients, the 2-year OS and
      locoregional control (LRC) rates were 41% and 30%, respectively. Multivariate
      analysis demonstrated that higher total dose, surgical resection, and nasopharynx
      site were significantly associated with improved LRC; surgical resection and
      nonsquamous histology were associated with improved OS. Seven patients (11%)
      experienced severe reirradiation-related toxicity, including one treatment
      attributed death. CONCLUSION: SRS reirradiation for head-and-neck cancer is
      feasible. This study demonstrates encouraging response rates with acceptable
      toxicity. Fractionated SRS reirradiation with concurrent chemotherapy in select
      patients warrants further study.

PMID- 20056342
TI  - Radiosurgery for brain metastases from unknown primary cancers.
AB  - PURPOSE: We evaluated the role of Gamma Knife stereotactic radiosurgery in the
      multidisciplinary management of brain metastases from an undiagnosed primary
      cancer. METHODS AND MATERIALS: Twenty-nine patients who had solitary or multiple
      brain metastases without a detectable primary site underwent stereotactic
      radiosurgery between January 1990 and March 2007 at the University of Pittsburgh.
      The median patient age was 61.7 years (range, 37.9-78.7 years). The median target
      volume was 1.0 cc (range, 0.02-23.6 cc), and the median margin radiosurgical dose
      was 16 Gy (range, 20-70 Gy). RESULTS: After radiosurgery, the local tumor control
      rate was 88.5%. Twenty four patients died and 5 patients were living at the time
      of this analysis. The overall median survival was 12 months. Actuarial survival
      rates from stereotactic radiosurgery at 1 and 2 years were 57.2% and 36.8%,
      respectively. Factors associated with poor progression-free survival included
      large tumor volume (3 cc or more) and brainstem tumor location. CONCLUSIONS:
      Radiosurgery is an effective and safe minimally invasive option for patients with
      brain metastases from an unknown primary site.

PMID- 20056343
TI  - Value of combined PET/CT for radiation planning in CT-guided percutaneous
      interstitial high-dose-rate single-fraction brachytherapy for colorectal liver
      metastases.
AB  - PURPOSE: To determine the additional value of fluorodeoxyglucose-positron
      emission tomography (PET) for clinical target volume definition in the planning
      of computed tomography (CT)-guided interstitial brachytherapy for liver
      metastases. PATIENTS AND METHODS: A total of 19 patients with liver metastases
      from colorectal cancer treated in 25 sessions were included in the present study.
      All patients had undergone fluorodeoxyglucose-PET for patient evaluation before
      interstitial CT-guided brachytherapy. A contrast-enhanced CT scan of the upper
      abdomen was obtained for radiation planning. The clinical target volume (CTV) was
      defined by a radiation oncologist and radiologist. After registration of the CT
      scan with the PET data set, the target volume was defined again using the fusion
      images. RESULTS: PET revealed one additional liver lesion that was not visible on
      CT. The median CT-CTV (defined using CT and magnetic resonance imaging) was 68
      cm(3) (range 4-260). The PET/CT-CTV (median, 78 cm(3); range, 4-273) was
      significantly larger, with a median gain of 24.5% (interquartile range, 2.1
      71.5%; p = .022). An increased CTV was observed in 15 cases and a decrease in 6;
      in 4 cases, the CT-CTV and PET/CT-CTV were equal. Incomplete dose coverage of
      PET/CT-CTVs was indicative of early local progression (p = .004); however, CT
      based radiation plans did not show significant differences in the local control
      rates when stratified by dose coverage. CONCLUSION: Retrospective implementation
      of fluorodeoxyglucose-PET for CTV specification for CT-guided brachytherapy for
      colorectal liver metastases revealed a significant change in the CTVs. Additional
      PET-positive tumor regions with incomplete dose coverage could explain unexpected
      early local progression.

PMID- 20056344
TI  - Cone-beam CT assessment of interfraction and intrafraction setup error of two
      head-and-neck cancer thermoplastic masks.
AB  - PURPOSE: To prospectively compare setup error in standard thermoplastic masks and
      skin-sparing masks (SSMs) modified with low neck cutouts for head-and-neck
      intensity-modulated radiation therapy (IMRT) patients. METHODS AND MATERIALS:
      Twenty head-and-neck IMRT patients were randomized to be treated in a standard
      mask (SM) or SSM. Cone-beam computed tomography (CBCT) scans, acquired daily
      after both initial setup and any repositioning, were used for initial and
      residual interfraction evaluation, respectively. Weekly, post-IMRT CBCT scans
      were acquired for intrafraction setup evaluation. The population random (sigma)
      and systematic (Sigma) errors were compared for SMs and SSMs. Skin toxicity was
      recorded weekly by use of Radiation Therapy Oncology Group criteria. RESULTS: We
      evaluated 762 CBCT scans in 11 patients randomized to the SM and 9 to the SSM.
      Initial interfraction sigma was 1.6 mm or less or 1.1 degrees or less for SM and
      2.0 mm or less and 0.8 degrees for SSM. Initial interfraction Sigma was 1.0 mm or
      less or 1.4 degrees or less for SM and 1.1 mm or less or 0.9 degrees or less for
      SSM. These errors were reduced before IMRT with CBCT image guidance with no
      significant differences in residual interfraction or intrafraction uncertainties
      between SMs and SSMs. Intrafraction sigma and Sigma were less than 1 mm and less
      than 1 degrees for both masks. Less severe skin reactions were observed in the
      cutout regions of the SSM compared with non-cutout regions. CONCLUSIONS:
      Interfraction and intrafraction setup error is not significantly different for
      SSMs and conventional masks in head-and-neck radiation therapy. Mask cutouts
      should be considered for these patients in an effort to reduce skin toxicity.

PMID- 20056345
TI  - 18Fluorodeoxyglucose PET is prognostic of progression-free and overall survival
      in locally advanced pancreas cancer treated with stereotactic radiotherapy.
AB  - PURPOSE: This study analyzed the prognostic value of positron emission tomography
      (PET) for locally advanced pancreas cancer patients undergoing stereotactic body
      radiotherapy (SBRT). PATIENTS AND METHODS: Fifty-five previously untreated,
      unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT
      sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the
      tumor was contoured and the maximum standardized uptake value (SUVmax) and
      metabolic tumor burden (MTB) were calculated using an in-house software
      application. High-SUVmax and low-SUVmax subgroups were created by categorizing
      patients above or below the median SUVmax. The analysis was repeated to form high
      MTB and low-MTB subgroups as well as clinically relevant subgroups with SUVmax
      values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age,
      chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was
      performed. RESULTS: For the entire population, median survival was 12.7 months.
      Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p
      <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and
      low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median
      survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0
      10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate
      analysis, clinical SUVmax was an independent predictor for overall survival (p =
      0.03) and progression-free survival (p = 0.03). CONCLUSION: PET scan parameters
      can predict for length of survival in locally advanced pancreas cancer patients.

PMID- 20056346
TI  - Incidence and correlates of radiation pneumonitis in pediatric patients with
      partial lung irradiation.
AB  - PURPOSE: To provide a radiation pneumonitis risk estimate and investigate the
      correlation of clinical and dosimetric factors in pediatric patients receiving
      chest irradiation. METHODS AND MATERIALS: A total of 122 patients diagnosed with
      sarcoma or Hodgkin lymphoma who received radiotherapy to the chest were evaluated
      for symptomatic radiation pneumonitis (Common Toxicity Criteria Grade 1 with
      respiratory symptom or higher grade). Pneumonitis data were collected from either
      prospective toxicity screenings as part of a clinical trial or through chart
      review. Dosimetric parameters including V(10)-V(25), mean lung dose, binned lung
      dose, and tissue complication probability models were used, as well as clinical
      features to correlate with the development of pneumonitis. RESULTS: The 1- and 2
      year cumulative incidence of symptomatic radiation pneumonitis for all patients
      was 8.2% and 9.1%, respectively. Nine patients experienced symptomatic Grade 1
      toxicity, and 2 experienced Grade 2. From univariate analysis, chemotherapy
      containing bleomycin (chi(2) test, p = 0.027) and V(24) (logistic regression, p =
      0.019) were the clinical and dosimetric factors that resulted in statistically
      significant differences in the occurrence of pneumonitis. The probability of
      pneumonitis increased more dramatically with increasing V(24) in patients
      receiving bleomycin than in those who did not. Adult tissue complication models
      did not differentiate pediatric patients with radiation pneumonitis from those
      without. CONCLUSIONS: The incidence of symptomatic radiation pneumonitis in
      pediatric patients is low and its severity mild. Parameters frequently used in
      adult radiation oncology provide some guidance as to risk, but pediatric patients
      warrant their own specific models for risk assessment, incorporating dosimetry
      and clinical factors.

PMID- 20056347
TI  - Parotid gland function after radiotherapy: the combined michigan and utrecht
      experience.
AB  - PURPOSE: To analyze the combined and updated results from the University of
      Michigan and University Medical Center Utrecht on normal tissue complication
      probability (NTCP) of the parotid gland 1 year after radiotherapy (RT) for head
      and-neck (HN) cancer. PATIENTS AND METHODS: A total of 222 prospectively analyzed
      patients with various HN malignancies were treated with conventional and
      intensity-modulated RT. Stimulated individual parotid gland flow rates were
      measured before RT and 1 year after RT using Lashley cups at both centers. A flow
      ratio <25% of pretreatment was defined as a complication. The data were fitted to
      the Lyman-Kutcher-Burman model. RESULTS: A total of 384 parotid glands (Michigan:
      157; Utrecht: 227 glands) was available for analysis 1 year after RT. Combined
      NTCP analysis based on mean dose resulted in a TD(50) (uniform dose leading to
      50% complication probability) of 39.9 Gy and m (steepness of the curve) of 0.40.
      The resulting NTCP curve had good qualitative agreement with the combined
      clinical data. Mean doses of 25-30 Gy were associated with 17-26% NTCP.
      CONCLUSIONS: A definite NTCP curve for parotid gland function 1 year after RT is
      presented, based on mean dose. No threshold dose was observed, and TD(50) was
      equal to 40 Gy.

PMID- 20056348
TI  - Computed tomography-guided high-dose-rate brachytherapy in hepatocellular
      carcinoma: safety, efficacy, and effect on survival.
AB  - PURPOSE: To determine the safety and efficacy of computed tomography (CT)-guided
      brachytherapy in hepatocellular carcinoma (HCC). METHODS AND MATERIALS: A total
      of 83 patients were recruited, presenting with 140 HCC- lesions. Treatment was
      performed by CT-guided high-dose-rate (HDR) brachytherapy with an iridium-192
      source. The primary endpoint was time to progression; secondary endpoints
      included local tumor control and overall survival (OS). A matched-pair analysis
      with patients not receiving brachytherapy was performed. Match criteria included
      the Cancer of the Liver Italian Program (CLIP) score, alpha-fetoprotein,
      presence, and extent of multifocal disease. For statistical analysis, Kaplan
      Meier and Cox regression were performed. RESULTS: Mean and median cumulative TTP
      for all patients (n = 75) were 17.7 and 10.4 months. Five local recurrences were
      observed. The OS after inclusion reached median times of 19.4 months (all
      patients), 46.3 months (CLIP score, 0), 20.6 months (CLIP score, 1) 12.7 months,
      (CLIP score, 2), and 8.3 months (CLIP score, >or=3). The 1- and 3-year OS were
      94% and 65% (CLIP score, 0), 69% and 12% (CLIP score, 1), and 48% and 19% (CLIP
      score, 2), respectively. Nine complications requiring intervention were
      encountered in 124 interventions. Matched-pair analysis revealed a significantly
      longer OS for patients undergoing CT-guided brachytherapy. CONCLUSION: Based on
      our results the study treatment could be safely performed. The study treatment
      had a beneficial effect on OS in patients with advanced HCC, with respect to (and
      depending on) the CLIP score and compared with OS in a historical control group.
      A high rate of local control was also observed, regardless of applied dose in a
      range of 15 to 25 Gy.

PMID- 20056349
TI  - Proton beam therapy for patients with medically inoperable stage I non-small-cell
      lung cancer at the university of tsukuba.
AB  - PURPOSE: To evaluate in a retrospective review the role of proton beam therapy
      for patients with medically inoperable Stage I non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: From November 2001 to July 2008, 55 medically
      inoperable patients with Stage I NSCLC were treated with proton beam therapy. A
      total of 58 (T1/T2, 30/28) tumors were treated. The median age of study
      participants was 77 years (range, 52-86 years). A total dose of 66 GyE in 10
      fractions was given to peripherally located tumors and 72.6 GyE in 22 fractions
      to centrally located tumors. RESULTS: The rates (95% confidence interval) of
      overall and progression-free survival of all patients and of local control of all
      tumors at 2 years were 97.8% (93.6-102.0%), 88.7% (77.9-99.5%), and 97.0% (91.1
      102.8%), respectively. There was no statistically significant difference in
      progression-free rate between T1 and T2 tumors (p = 0.87). Two patients (3.6%)
      had deterioration in pulmonary function, and 2 patients (3.6%) had Grade 3
      pneumonitis. CONCLUSION: Proton beam therapy was effective and well tolerated in
      medically inoperable patients with Stage I NSCLC.

PMID- 20056350
TI  - Toxicity and outcome results of a class solution with moderately hypofractionated
      radiotherapy in inoperable Stage III non-small cell lung cancer using helical
      tomotherapy.
AB  - PURPOSE: To prospectively assess the feasibility, toxicity, and local control of
      a class solution protocol of moderately hypofractionated tomotherapy in Stage
      III, inoperable, locally advanced non-small-cell lung cancer patients. METHODS
      AND MATERIALS: Eligible patients were treated according to a uniform class
      solution (70.5 Gy in 30 fractions) with fixed constraints and priorities using
      helical tomotherapy. Toxicity monitoring was performed using the Radiation
      Therapy Oncology Group criteria and the National Cancer Institute Common
      Terminology Criteria and Adverse Events (CTCAE) version 3.0. Pulmonary function
      tests were performed at the start and repeated at 3 months after treatment.
      RESULTS: Our class solution resulted in a deliverable plan in all 40 consecutive
      patients. Acute Grade 3 lung toxicity was seen in 10% of patients. Two patients
      died during acute follow-up with pulmonary toxicity. Correlations were found
      between changes in pulmonary function test results and mean lung dose or the lung
      volume receiving 20 Gy (V(20)). The correlation was strongest for lung diffusion
      capacity for carbon monoxide. A V(20) of >27% and >32% were predictive for Grades
      2 and 3 acute lung toxicity respectively (p < 0.05). Late Grade 3 toxicity was
      exclusively pulmonary, with an incidence of 16%. Overall Grade 3 lung toxicity
      correlated with a mean lung dose of >18 Gy and a median lung dose of >5 Gy (p <
      0.05). Median survival was 17 months, and the 1-year and 2-year local progression
      free survivals were 66% and 50%, respectively. CONCLUSION: The current class
      solution using moderately hypofractionated helical tomotherapy in patients with
      locally advanced non-small-cell lung cancer is feasible. Toxicity was acceptable
      and in line with other reports on intensity-modulated radiotherapy. The local
      progression-free survival was encouraging considering the unselected population.

PMID- 20056351
TI  - Estimating optimal dose of twice-weekly gemcitabine for concurrent
      chemoradiotherapy in unresectable pancreatic carcinoma: mature results of GEMRT
      01 Phase I trial.
AB  - PURPOSE: To accurately determine the maximal tolerated dose, feasibility, and
      antitumor activity of concurrent chemoradiotherapy including twice-weekly
      gemcitabine in patients with unresectable pancreatic adenocarcinoma. METHODS AND
      MATERIALS: Eligible patients with histologically proven adenocarcinoma of the
      pancreas were included in this Phase I trial. Radiotherapy was delivered to a
      total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was
      administered during the 5 weeks of radiotherapy, from an initial dose of 30
      mg/m(2). The gemcitabine doses were escalated in 10-mg/m(2) increments in a three
      plus-three design, until dose-limiting toxicities were observed. RESULTS: A total
      of 35 patients were included in the trial. The feasibility of chemoradiotherapy
      was high, because all the patients received the planned total radiation dose, and
      26 patients (74%) received > or = 70% of the planned chemotherapy dose. The mean
      total delivered dose of gemcitabine was 417 mg/m(2) (i.e., 77% of the prescribed
      dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m(2). Of
      the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%).
      Overall, the median survival and the 6-, 12-, and 18-month survival rates were
      10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly
      longer in patients with an initial performance status of 0 or 1 (p = .004).
      CONCLUSION: Our mature data have indicated that gemcitabine doses can be
      increased < or = 70 mg/m(2), when delivered twice-weekly with concurrent
      radiotherapy. This combination shows promises to achieve better recurrence-free
      and overall survival. These results will serve as a basis for further
      implementation of the multimodal treatment of locally advanced pancreatic
      carcinoma.

PMID- 20056352
TI  - Surviving hypopharynx-larynx carcinoma in the era of IMRT.
AB  - PURPOSE: Outcome in locoregionally advanced laryngeal carcinoma and
      hypopharyngeal carcinoma after conventional radiation techniques is known for
      modest disease control and considerable late toxicity. Considering the lack of
      standardization in prescription dose for intensity-modulated radiotherapy (IMRT),
      we aimed to compare the results after our methods of simultaneously integrated
      boost IMRT with published results. METHODS AND MATERIALS: Between March 2002 and
      December 2008, 65 hypopharyngeal, 31 supraglottic, and 27 locoregionally advanced
      glottic tumor patients underwent definitive IMRT (with simultaneous chemotherapy
      in 86%). Of these, 64% presented with locoregionally advanced disease. Mean
      follow-up was 26 months (range, 3-83 months), with a median of 21 months.
      Treatment (2.0-2.2 Gy per fraction, 66-72.6 Gy) followed a prospectively defined
      protocol. If the boost volume included more than half of the larynx or a
      substantial part of the pharynx, dose was limited to 2.0 Gy per fraction.
      RESULTS: The 2-year local, nodal, and locoregional control (LRC) rates for the
      entire cohort were 82%, 90%, and 77%, respectively; the disease-free and overall
      survival rates were 75% and 83%, respectively. The ultimate 2-year LRC rate,
      including salvage surgery, was 86%. Laryngectomy was required in 2 LRC patients
      needing tracheostoma already before; 2 further LRC patients needed tracheostomy
      before IMRT and remained tracheostoma dependent, and 3 patients remained feeding
      tube dependent after IMRT. Salvage laryngectomy was successful in 8 of 11. Of all
      123 patients, 91 patients (74%) are locoregionally controlled and live with a
      functional laryngopharynx. CONCLUSIONS: Simultaneously integrated boost IMRT with
      limited acceptance of dose inhomogeneity resulted in very satisfactory disease
      control despite a slight left shift of planning target volume curves on the dose
      volume histogram. Considering the treatment tolerance, a careful increase in dose
      in our patients seems possible. Dose-volume comparisons remain difficult because
      no international standards have been defined for contouring and volume-related
      dose distribution.

PMID- 20056353
TI  - Involved-lesion radiation therapy after chemotherapy in limited-stage head-and
      neck diffuse large B cell lymphoma.
AB  - PURPOSE: To report treatment outcomes after combined-modality therapy in patients
      with Stage I/II head-and-neck (HN) diffuse large B cell lymphoma (DLBL). METHODS
      AND MATERIALS: Eighty-six eligible patients received sequential chemotherapy and
      involved-lesion radiation therapy from 1995 to 2006. After a median of four
      cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or
      rituximab-plus-CHOP chemotherapy, a median of 41.4 Gy was delivered to the known
      initial gross lesion with adequate margin (2 to 3 cm). RESULTS: After a median
      follow-up of 57 months, eight treatment failures were observed: distant
      metastasis in 8 patients; and locoregional failure in 4 patients. Among the 4
      patients with locoregional failure, 3 presented with in-field failures, and 1
      both in-field and out-of-field failure (contralateral neck). Rates of overall
      survival (OS) and freedom from progression (FFP) at 10 years were 74.1% and
      88.9%, respectively. There was no severe side effect except 1 patient with Grade
      3 mucositis during and after completion of radiation therapy. Multivariate
      analyses showed that absence of B symptom (p = 0.022) and normal lactate
      dehydrogenase (p = 0.017) were related to favorable OS, age >60 years (p = 0.033)
      was related to favorable FFP, and international prognostic index of 0 or 1 was
      related to favorable OS (p = 0.003) and FFP (p = 0.03). CONCLUSION: This study
      demonstrated that patients with Stage I/II HN DLBL did not need whole-neck
      irradiation. Involved-lesion radiation therapy might reduce radiation toxicity
      with favorable treatment results.

PMID- 20056354
TI  - Urinary obstruction in prostate cancer patients from the Dutch trial (68 Gy vs.
      78 Gy): relationships with local dose, acute effects, and baseline
      characteristics.
AB  - PURPOSE: To investigate the relationship between late urinary obstruction and the
      details of the dose distribution of irradiated prostate cancer patients, taking
      into account their baseline symptoms and acute complaints. PATIENTS AND METHODS:
      We selected patients from the Dutch multicenter trial randomized between 68 Gy
      and 78 Gy, for whom toxicity data and dose data were available (n = 557). The
      absolute dose surface parameters of the delineated bladder were calculated. Next,
      we constructed three-dimensional dose maps of the area around the prostate,
      providing an approximate identification of the corresponding anatomic locations.
      The dose difference maps were constructed by subtracting the mean dose maps of
      the patients with and without late urinary obstruction. Selected local dose
      points were analyzed using Cox regression analysis. RESULTS: Urinary obstruction
      was scored for 40 patients, including 19 of 296 patients who received 68-72 Gy
      and 21 of 261 patients who received 76-78 Gy. A total of 19 events occurred
      within 2 years after irradiation and 21 events after 2 years. The bladder surface
      receiving >or=80 Gy predicted (p <.01) the occurrence of obstruction within 2
      years. The dose difference map indicated highly significant differences in the
      bladder neck situated in the trigonal region (p < .001) that were especially
      predictive of obstruction after 2 years and of the diagnosis of bladder neck
      obstruction. Baseline complaints and transurethral resection of the prostate and
      acute complaints were mainly predictive for obstruction within 2 years.
      CONCLUSION: Relatively early events of urinary obstruction were associated with
      urinary problems existing before RT, acute toxicity, previous transurethral
      resection of the prostate, and hotspots in the bladder. Events after 2 years were
      associated with the local dose in the trigonal area.

PMID- 20056355
TI  - Analysis of prognostic factors after yttrium-90 radioembolization of advanced
      hepatocellular carcinoma.
AB  - PURPOSE: To analyze which patient-, tumor-, and treatment-related factors may
      influence outcome after (90)Y radioembolization ((90)Y-RE) for hepatocellular
      carcinoma (HCC). PATIENTS AND METHODS: Seventy-two consecutive patients with
      advanced HCC treated with (90)Y-RE were studied to detect which factors may have
      influenced response to treatment and survival. RESULTS: Median overall survival
      was 13 months (95% confidence interval, 9.6-16.3 months). In univariate analysis,
      survival was significantly better in patients with one to five lesions (19 vs. 8
      months, p = 0.001) and in patients with alpha-fetoprotein <52 UI/mL (24 vs. 11
      months, p = 0.002). The variation in target tumor size and the appearance of new
      lesions were analyzed among 50 patients with measurable tumors. A decrease in
      target tumor size was observed in most patients, and the intensity of such
      decrease was not associated with any of the factors under study. Patients who
      developed new lesions in the treated liver (and also in the nontargeted liver) at
      month 3 more frequently had more than five nodules, bilobar disease, and alpha
      fetoprotein >52 UI/mL, and their survival in the multivariate analysis was
      significantly worse (hazard ratio, 4.7; 95% confidence interval, 13-1.73) (p =
      0.002). CONCLUSIONS: Yttrium-90 radioembolization results in control of target
      lesions in the majority of patients with HCC but does not prevent the development
      of new lesions. Survival of patients treated with (90)Y-RE seems to depend
      largely on factors related to the aggressiveness of the disease (number of
      nodules, levels of alpha-fetoprotein, and presence of microscopic disease).

PMID- 20056356
TI  - First isolation of a newly described Mycobacterium insubricum from freshwater
      fish.
AB  - Non-tuberculous or potentially pathogenic mycobacteria are ubiquitous in a water
      environment and are responsible for several diseases in animals and humans known
      as mycobacterioses. This report describes the first isolation of the novel
      species Mycobacterium insubricum in clinically healthy freshwater fish (Tinca
      tinca) in the Czech Republic which is the first to be derived from non-human
      sources reported in the literature.

PMID- 20056357
TI  - Genetic diversity and prevalence of netB in Clostridium perfringens isolated from
      a broiler flock affected by mild necrotic enteritis.
AB  - This study was undertaken to examine the genetic diversity of Clostridium
      perfringens isolated from a single broiler flock reared without in-feed
      antimicrobials (antibacterial growth promoters and anticoccidials) and affected
      by mild necrotic enteritis (NE). We used pulsed-field gel electrophoresis (PFGE)
      to investigate the genetic diversity of C. perfringens isolates from broilers of
      varying disease status, and from litter. The prevalence of the toxin gene netB
      was also investigated. Altogether 32 PFGE genotypes were found among 88 isolates.
      Several genotypes were detected in C. perfringens-associated organ lesions from
      chickens that were sampled at random and alive without clinical symptoms,
      suggesting that these genotypes proliferated concurrently in such lesions. More
      than 90% of all isolates from NE-specific organ lesions carried netB which codes
      for a recently described pore-forming toxin. NetB positive isolates were less
      predominant in non-lesion samples from broilers affected by NE, and found
      infrequently or not at all in healthy birds and isolates from litter. These
      findings show that the presence of netB in C. perfringens strains is associated
      with NE and suggest that mild NE differs from severe NE with regard to C.
      perfringens genotype diversity.

PMID- 20056358
TI  - Early assessment of visual function in preterm infants: how early is early?
AB  - BACKGROUND: Several studies reported on various aspects of visual function at
      term age and in the first months after birth but less has been reported in
      preterm infants before they reach termequivalent age. AIMS: To assess the
      suitability of a battery of tests of visual function for use in infants born at
      <33weeks gestation (GA) and assessed before 34weeks post-menstrual age (PMA); to
      evaluate the distribution of the findings according to GA, and to compare the
      data with those previously published on preterm infants assessed at 35weeks PMA.
      STUDY DESIGN: Cross-sectional study. SUBJECTS: Sixty-four preterm infants with a
      GA <33weeks were studied. OUTCOME MEASURES: We used a battery of visual function
      tests previously validated at 35 and 40weeks PMA in low-risk preterm infants. All
      the infants in this current study underwent the same assessment before 34weeks
      PMA. RESULTS: Before 31weeks PMA most infants could not be reliably assessed
      because of clinical instability, whilst after 31weeks PMA most infants could be
      assessed and they showed progressive maturation in their responses with PMA. Some
      items (spontaneous ocular motility, horizontal tracking, tracking a coloured
      stimulus, and ocular fixation) showed similar results at 32-33weeks PMA to those
      found in low-risk preterm at 35weeks PMA. Ocular movements to a target and arc
      tracking were the items with the most immature responses. CONCLUSIONS: Our
      results provide further evidence that a structured assessment of visual function
      can be used in clinical routine and for research purposes in infants as young as
      31weeks PMA.

PMID- 20056359
TI  - Seasonal effect on sperm messenger RNA profile of domestic swine (Sus Scrofa).
AB  - Seasonal infertility is a well-known problem in the modern swine (Sus scrofa)
      industry. The molecular mechanisms responsible for thermal effects on
      spermatogenesis are, however, just beginning to be elucidated. The existence of
      specific messenger RNA (mRNA) remnants contained within freshly ejaculated sperm
      has been identified in several species. Investigators have obtained differential
      RNA profiles of infertile men compared with fertile individuals; however, there
      are limited to the probes, which are mostly derived from nucleic acids of
      testicular tissues of either human or mice. The objective of this study was to
      investigate mRNA remnants from ejaculated sperm of the domestic swine and uncover
      important clues regarding the molecular regulation of spermatogenesis under
      environmental thermo-impacts. We utilized the remnant mRNA collected from swine
      ejaculated sperm as the target source to detect the global gene expression in
      summer and in winter by swine sperm-specific oligonucleotide microarray. Sixty
      seven transcripts were differentially expressed with statistical differences
      between seasons of sperm samples collected, including forty-nine in winter
      (49/67) and eighteen in summer (18/67). There were only 33 of these transcripts
      that could be annotated to gene ontology hierarchy with the database of Homo
      sapiens and their functions mostly were involved in variety of metabolic
      processes. Moreover, these studies also confirmed that significant differences of
      gene expression profiles were found in swine sperm when comparisons were made
      between ejaculates collected during the winter and the summer season under the
      subtropical area such as Taiwan. Even though most of the genes found in our
      experiments are still poorly understood in terms of their true functions in
      spermatogenesis, bioinformatics analysis suggested that they are involved in a
      broad spectrum of biochemical processes including gamete generation. These
      concordant profiles should permit the development of a non-invasive testing
      protocol to assess the functional capacity of sperm as well as a new molecular
      selection scheme for fine breeding swine.

PMID- 20056360
TI  - Efficacy of Ovsynch protocol in cyclic and acyclic Egyptian buffaloes in summer.
AB  - The aim of the present study was to evaluate the efficacy of an Ovsynch protocol
      in the cyclic and non-cyclic Egyptian buffaloes in the summer. The present study
      was carried out on 21 Egyptian pluriparous buffalo cows (11 cyclic and 10
      acyclic) and 8 heifers (5 cyclic and 3 acyclic). All animals were administered
      100 microg GnRH i.m. at Day 0, 500 microg of PGF2 proportional, variant i.m. at
      Day 7 and a second dose (100 microg) of GnRH i.m. at Day 9. Ovarian structures of
      the animals were recorded by means of transrectal ultrasonography (6-8 MHz linear
      array transducer) daily from Day 0 (before treatment) to Day 9 (the second GnRH
      administration) and thereafter, at 12-h interval till ovulation or for a maximum
      of 48 h. After ultrasound examination, a blood sample was taken daily from each
      animal for progesterone analysis. The buffalo cows were inseminated at 16-20 h
      after 2nd GnRH administration. After the first administration of GnRH, 46% (5 of
      11) of cyclic and 50% (5 of 10) of acyclic cows and 40% (2 of 5) of cyclic and
      33% (1 of 3) of acyclic heifers responded by ovulation or luteinization of the
      follicles. The mean diameters (+/-S.E.M.) of the follicles in the responding cows
      and heifers were significantly higher than those in non-responding animals (9.7
      +/- 0.4 mm vs. 6.7 +/- 0.6 mm, P < 0.0001; 11.1 +/- 1.5 mm vs. 7.3 +/- 0.7 mm, P
      < 0.05, respectively). After the second administration of GnRH, 81% (9 of 11) of
      cyclic and 60% (6 of 10) of acyclic cows and 80% (4 of 5) of cyclic and 33% (1 of
      3) of acyclic heifers ovulated, respectively. Ovulations occurred earlier (P =
      0.059) and over a wider range of time in the non-cyclic cows (26 +/- 4.8 h;
      range: 12-36 h) and in a heifer (12 h,) than in the cyclic cows (34.7 +/- 1.3 h;
      range 24-36 h) and heifers (33 +/- 3 h; range: 24-36 h). The conception rate was
      18% (2 of 11) and 0% (0 of 10) in cyclic and non-cyclic cows, respectively. In
      conclusion, the Ovsynch protocol could be used effectively for synchronization of
      ovulation in cyclic cows and heifers in summer.

PMID- 20056361
TI  - The molecular basis of longevity, and clinical implications.
AB  - The determinants of length of life are multifactorial and involve complex
      processes, most of which are not as yet understood completely. Tremendous
      advances have, however, been made in recent times in understanding some of the
      key molecular mechanisms that influence ageing and lifespan. Herein we highlight
      many of the more important findings and their potential clinical implications.
      Most of the intracellular factors involved in the ageing process, such as members
      of the sirtuin family, as well as insulin and insulin-like growth factor-I and
      their genes, are part of interconnected pathways. The manipulation of these and
      other genes in animal models can increase or decrease lifespan. Transcriptional
      and post-transcriptional regulatory mechanisms, some of which involve microRNAs,
      as well as modifications to chromatin and histones, can influence longevity. A
      decline in the function of stem cells might also be responsible for some aspects
      of mammalian ageing. Calorie restriction, polyphenols such as resveratrol,
      rapamycin, spermidine and angiotensin I converting enzyme inhibitor, are able to
      increase lifespan by modulation of branches of the longevity pathways. Molecular
      genetic studies of long-lived subjects have identified several potential
      candidate genes, but genetic research on ageing is in its infancy. Large genome
      wide association studies should provide insights. Although new biomarkers for
      ageing and health, such as ones that might reveal telomere dysfunction, have been
      described, advances in the genetics and molecular biology of longevity will
      require interdisciplinary approaches if the much-hoped for success in alleviating
      the diseases of ageing, and an extension of both lifespan and healthspan is to be
      achieved.

PMID- 20056362
TI  - Demographics of suicide victims in Sweden in relation to their blood-alcohol
      concentration and the circumstances and manner of death.
AB  - Specimens of blood and other body fluids were obtained at autopsy from all deaths
      in Sweden classified as suicide covering a 10-year period (N=11,441 cases). The
      mean age (+/-standard deviation, SD) of the victims was 51.3+/-18.8 years with a
      clear predominance of males 71% (mean age 51.3+/-18.8 years) compared with 29%
      females (mean age 51.4+/-18.9 years). The concentration of ethanol in blood
      samples was determined in duplicate by headspace gas chromatography and a mean
      blood-alcohol concentration (BAC) of 0.1g/L (10mg/100mL) was the cut-off used to
      identify ethanol positive cases. The suicides were coded (ICD-9) as self
      poisonings (N=2462, 22%), hanging (N=4474, 39%), asphyxia by gas (N=509, 4.4%),
      drowning (N=803, 7.0%), gun shot (N=1307, 11.4%), fall from height (N=632, 5.5%),
      self-inflicted cuts or sharp-force injury (N=363, 3.1%) and miscellaneous ways
      (N=891, 7.8%). On average 34% of all suicide victims in Sweden had consumed
      alcohol before death, 36% of the males and 31% of the females had a positive BAC.
      The mean (median) concentration of alcohol in femoral blood for men was 1.34g/L
      (1.3g/L) compared with 1.25g/L (1.1g/L) for women. Many victims were heavily
      intoxicated and the 90th percentiles of the BAC distributions ranged from 2.3 to
      2.8g/L depending on manner of death. Elevated blood-alcohol was most prevalent in
      poisoning deaths (45%) and gas asphyxia (51%) and least prevalent in falls from
      height (19%) and sharp-force injury (18%). Toxicological analysis for presence of
      drugs other than alcohol showed a predominance of paracetamol, SSRI
      antidepressants, anti-psychotics, sedative-hypnotics, and centrally acting
      opioids. A host of psycho-social factors drive a person to commit suicide and one
      of the catalysts is over-consumption of alcohol and acute alcohol intoxication.
      Heavy drinking leads to a loss of inhibitions, impulsive behaviour, poor judgment
      and a tendency to take risks, all of which might increase the propensity of
      predisposed individuals to take their own lives.

PMID- 20056363
TI  - Potential of IRMS technology for tracing gamma-butyrolactone (GBL).
AB  - Popularity of gamma-hydroxybutyric acid (GHB) is fairly stable among drug users,
      while the consumption of its chemical precursor, gamma-butyrolactone (GBL), is a
      growing phenomenon. Although conventional analytical methods allow to detect this
      substance in various matrices, linking a trace and a source is still a difficult
      challenge. However, as several synthesis pathways and chemical precursors exist
      for the production of GBL, its carbon isotopic signature may vary extensively.
      For that purpose, a method has been developed to determine the carbon isotopes
      content of GBL by means of gas chromatography/combustion/isotope ratio mass
      spectrometry (GC/C/IRMS). The delta(13)C-values of 19 bulk samples purchased
      worldwide were in the range from -23.1 to -45.8 per thousand (SD<0.3 per
      thousand). Furthermore, testing on the purification of GBL by distillation has
      not been found to be consistent with such a large range of delta(13)C-values,
      which are likely to result from the isotopic composition of the organic
      precursors used to produce GBL together with the kinetic isotope effect
      associated with the synthesis routes. Finally, inter- and intra-variability
      measurements of the delta(13)C-values demonstrated the high potential of IRMS for
      discriminating between seizures of GBL and for source determination.

PMID- 20056364
TI  - Gas chromatography-mass spectrometry assay for the simultaneous quantification of
      drugs of abuse in human placenta at 12th week of gestation.
AB  - We describe the development and validation of a method for the quantification of
      drugs of abuse, using gas chromatography-mass spectrometry (GC/MS), in human
      placenta. Concentration ranges covered were 5-500 ng/g for amphetamine,
      methamphetamine, MDMA, methadone, cocaine, benzoylecgonine, cocaethylene,
      morphine, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol, nicotine, and cotinine.
      Intra-assay and inter-assay imprecisions were less than 15.7% for lower quality
      control samples and less than 14.9% for medium and high quality control samples.
      Recovery range was 36.2-83.7%. Placenta samples were kept at -80 degrees C until
      analysis; analytes were stable after three freeze-thaw cycles (samples stored at 
      20 degrees C). This accurate and precise assay has sufficient sensitivity and
      specificity for the analysis of specimens collected from women who voluntarily
      terminated their pregnancy at 12th week of gestation. The method has proven to be
      robust and accurate for the quantification of the principal recreational drugs of
      abuse in this period of the prenatal life. This is the first report that
      highlights the presence of drugs of abuse during the first trimester of
      gestation.

PMID- 20056365
TI  - Assessment of dental maturity of western Chinese children using Demirjian's
      method.
AB  - Age estimation plays an important role in forensic medicine and orthodontics.
      Dental maturity, expressed as dental age, is one of the common indices for age
      estimation. Demirjian's method, first described in 1973 and based on a large
      number of French-Canadian samples, is one of the most widely used methods for
      dental age assessment. The aim of this study is to evaluate the applicability of
      Demirjian's method for dental age estimation in western Chinese children. Digital
      panoramic radiographs of 445 children of western Chinese origin, ranging from 8
      to 16 years old, were assessed in Demirjian's method. The dental maturity scores
      (DMSs) and dental ages of all the subjects were calculated by a single observer.
      The dental ages were compared to the chronological ages with a paired t-test. The
      general trend in this research showed that the western Chinese children
      demonstrated a more advanced dental age compared to French-Canadian children as
      previously presented by Demirjian. The mean difference in each age group between
      the dental age and chronological age ranged from 0.0071 to 1.2500 years in girls
      and from -1.0000 to 1.3000 years in boys. The standards of dental age assessment
      provided by Demirjian for French-Canadian children may be not suitable for
      western Chinese children. As a result, specific standards of dental age
      assessment should be established for this population.

PMID- 20056366
TI  - Polymorphic microsatellites for forensic identification of agarwood (Aquilaria
      crassna).
AB  - Tropical agarwood (Aquilaria) is in danger of extinction in the wild due to
      illegal logging. Its resin (Gaharu) is used for the production of highly valued
      incense throughout Asia. We have isolated and characterized microsatellite loci
      of Aquilaria crassna to detect the geographic origin of agarwood for forensic
      applications using a modified enrichment procedure based on the capture of
      repetitive sequences from restricted genomic DNA. We assessed the polymorphisms
      of five microsatellites amplified from fresh leaves of 22 trees from seven
      plantations in Vietnam and Thailand and dried leaves of a herbarium specimen of
      one wild tree. Cross specificity of these markers was confirmed on two related
      Aquilaria species occurring in China and Vietnam and one microsatellite locus was
      successfully amplified from wood and incense samples. Four of the loci were
      polymorphic and the number of alleles ranged from 3 to 15. The loci characterized
      here can provide a starting point for forensic identification of traded material
      and certification of sustainably produced agarwood.

PMID- 20056367
TI  - [Embolization of recurrent bleeding jejunal varices].
AB  - We report a case of recurrent digestive haemorrhage due to bleeding ectopic
      jejunal varices complicating portal hypertension in a 51-year-old cirrhotic
      patient, treated 1 year ago by transjugular intrahepatic porto-systemic shunt
      (TIPS) for the same problem. Successful embolisation with coils, of ectopic
      varices, was performed using original transjugular and trans-TIPS route, without
      complication, and no recurrence during a follow-up of 24 months.

PMID- 20056368
TI  - CT imaging spectrum of pancreatic serous tumors: based on new pathologic
      classification.
AB  - PURPOSE: The aim of this study is to retrospectively analyze the variety of CT
      findings based on new pathologic classification. MATERIALS AND METHODS: During a
      10-year period, 59 histopathologically proven pancreatic SCTs and 13 SCTs
      confirmed with typical image findings and strict clinical criteria were enlisted.
      Two radiologists analyzed CT images for the following items in consensus:
      location, size, outer margin, tumor shape, the presence of mural nodule,
      communication with main pancreatic duct (MPD), the presence and extent of MPD
      dilatation, calcification, central scar, and attenuation on pre- and post
      contrast CT images. In addition, typicality of CT findings was determined. A
      typical finding was defined as a honeycomb appearance without or with oligocystic
      portion. In the cases with atypical features, the type of atypical features and
      differential diagnosis were recorded. For the shape of the tumor, tumors were
      categorized into the following groups: honeycomb without or with oligocystic,
      pleomorphic, purely oligolocular, unilocular cystic, hypovascular solid,
      hypervascular solid without or with oligocystic portion, and fingerlike cystic
      patterns. RESULTS: 28 SCTs (38.9%) presented a honeycomb appearance with (n=14)
      or without oligocystic portion (n=14) and were classified as typical cases. The
      remaining 44 atypical cases (61.1%) presented the following: purely oligolocular
      pattern in 18; hypervascular solid without (n=7) or with oligocystic portion
      (n=2) in 9; pleomorphic in 8; unilocular cystic in 7; and fingerlike cystic
      pattern in 2. Most of the lesions manifesting as hypervascular solid lesions were
      confused with true solid hypervascular tumors such as neuroendocrine tumors or
      solid pseudopapillary tumors. For most of the remaining atypical lesions,
      mucinous cystic neoplasm or branch duct type IPMN were included as a differential
      diagnosis. CONCLUSION: Serous cystic tumors of the pancreas can have variable CT
      appearances ranging from compactly solid hypervascular to clearly unilocular
      cystic, which reflect a varied macroscopic morphology. Only 38.9% of the SCTs
      show traditional typical CT features whereas a considerable proportion (61.1%) of
      SCTs showed atypical appearances, providing diagnostic challenges to
      radiologists.

PMID- 20056369
TI  - MR imaging for blunt pancreatic injury.
AB  - OBJECTIVE: To study the MR imaging features of blunt pancreatic injury. MATERIALS
      AND METHODS: Nine patients with pancreatic injury related to blunt abdominal
      trauma confirmed by surgery performed MR imaging. Two abdominal radiologists
      conducted a review of the MR images to assess pancreatic parenchymal and
      pancreatic duct injury, and associated complications. RESULT: Diagnostic quality
      MR images were obtained in each of the nine patients. In the nine patients,
      pancreatic fracture, laceration and contusion were depicted on MR imaging in
      five, one and three patients, respectively. There were six patients with
      pancreatic duct disruption, eight patients with peripancreatic fluid collections,
      and four patients with peripancreatic pseudocyst or hematoma, respectively. All
      of the MR imaging findings was corresponded to surgical findings. CONCLUSION: MR
      imaging is an effective method to detect blunt pancreatic injury and may provide
      information to guide management decisions.

PMID- 20056370
TI  - Begin the BEGAN (The Brown Educational Guide to the Analysis of Narrative) - a
      framework for enhancing educational impact of faculty feedback to students'
      reflective writing.
AB  - OBJECTIVE: The study aim was the development of a method to further enhance the
      educational benefit of medical students' reflective writing. The setting is a
      Doctoring course at the Warren Alpert Medical School of Brown University, which
      includes reflective writing assignments, termed "field notes", combining
      students' reflective writing with ongoing individualized feedback from small
      group faculty. METHODS: Three-year (2005-2008) iterative process with three
      stages of immersion, analysis, and revision that resulted in the analysis
      framework. An interdisciplinary team composed of the four authors with
      backgrounds in narrative medicine, qualitative research, psychology, and medical
      education analyzed 12 first and second year students' selected field notes in
      iterative cycles. In each cycle, consultations with small group faculty and
      content experts were conducted to further validate the emergent framework.
      RESULTS: This process culminated in the creation of the Brown Educational Guide
      to Analysis of Narrative (BEGAN) framework, a guide for crafting feedback to
      students' reflective writing, and the integration of the BEGAN framework into the
      faculty and student manuals for the Doctoring Course in 2008-2009. CONCLUSIONS:
      We propose the BEGAN framework as a useful innovative tool that can be
      incorporated in reflective writing curricula in the field of health professions
      education. It is tailored to support the educational impact of the course through
      additional scaffolding of student writing, and the robust process it delineates
      for crafting of faculty feedback. Providing systematic feedback to enhance
      reflective writing may represent the path forward in fostering professional
      development through reflection in health professions education. PRACTICE
      IMPLICATIONS: The BEGAN can be incorporated in reflective writing curricula in
      the field of health professions education. It is a springboard for the necessary
      next steps of development and research into the acquisition of reflective and
      narrative competence in the emerging professional.

PMID- 20056371
TI  - Everything you always wanted to know about HPV (but could not ask your doctor).
AB  - OBJECTIVE: To investigate specific information needs of people who search for
      information about the human papillomavirus (HPV) on the Internet. METHODS: We
      performed a qualitative analysis of the e-mail questions asked by the visitors of
      a website with evidence-based information about HPV. The website, hosted by
      Antwerp University, provided basic information on epidemiology and natural
      history of HPV in women and men, diagnostic and treatment options, screening, and
      vaccination. If visitors did not find an answer to their questions, they could
      mail their question to an e-mail address associated with the website. RESULTS: We
      received 713 questions posed by 527 e-mail correspondents. The following themes
      emerged as most important: transmission of HPV, the HPV vaccine, the natural
      history of the virus, the vicious circle (re-infection between partners), HPV
      detection in men and women, treatment of men and women, incubation time,
      pregnancy/fertility, genital warts (in)fidelity, and symptoms of HPV infection.
      CONCLUSION: Both men and women are seeking health information on HPV on the
      Internet, often after being counseled by a health care provider. PRACTICE
      IMPLICATIONS: Practitioners should be prepared for questions on the themes that
      concern people most. Practitioners may play a role in guidance towards reliable
      sources of information.

PMID- 20056372
TI  - Fetal alcohol syndrome: knowledge and attitudes of family medicine clerkship and
      residency directors.
AB  - Fetal alcohol spectrum disorders (FASD) are the leading preventable causes of
      developmental disabilities with serious permanent consequences. Regardless of the
      increased awareness of fetal alcohol syndrome (FAS), 13% of women in the United
      States drink alcohol during pregnancy. Health care professionals do not routinely
      assess the frequency and quantity of alcohol use by their patients. This study
      examined the knowledge, skills, and practices of family medicine residency and
      clerkship directors and assessed the time devoted and format of FAS curricula in
      the programs. A self-administered anonymous survey was sent to the residency and
      clerkship directors (N=571). Response rate of clerkship directors was 52% and
      residency directors 46%. Both groups showed high level of knowledge of FASD and
      of alcohol counseling practices for pregnant women. Although almost two thirds of
      the residency programs had FASD integrated in the curriculum, an equivalent
      fraction of predoctoral programs did not. More than half of the clerkship
      directors without FASD in their curriculum agreed that a need exists for its
      inclusion. These findings raise important medical education and policy issues and
      provide insight into the disparity in FASD content of curricula between
      predoctoral and family medicine residency programs in the United States. The role
      of physician counseling in primary prevention of FAS should continue to be
      stressed in predoctoral and residency education.

PMID- 20056373
TI  - Breast pumping and lactational state exert differential effects on ethanol
      pharmacokinetics.
AB  - Prior research revealed that breast stimulation altered the way the lactating
      body handles alcohol. Its effects depended upon when it occurred relative to
      drinking. The goal of the present study was to determine whether breast pumping
      works independently of the physiological and metabolic changes that accompany
      lactation. To this end, we tested 12 women when they were exclusively
      breastfeeding 3-5-month-old infants and then again several months after lactation
      had ceased. Subjects were randomly assigned to one of two groups that differed in
      the timing of breast pumping relative to drinking a 0.4g/kg dose of alcohol: one
      group breast pumped 0.6h after drinking (pumped after group) and the other pumped
      1h before drinking (pumped before group). For each reproductive stage, subjects
      were tested on 2 separate days, consuming a standardized meal 1 h before drinking
      during 1 test day and remaining fasted during the other. Breath alcohol
      concentrations (BrAC) and temperature readings were obtained before and at fixed
      intervals after drinking. Pumping before drinking significantly decreased BrAC
      during both reproductive stages, whereas pumping after drinking resulted in
      different BrAC time curves during lactation when compared with after lactation.
      That is, levels were significantly lower during the descending phase of the time
      curve during than after lactation. The interactions between pumping and
      reproductive stage were most apparent during fed condition. Furthermore, women
      were more sensitive to hypothermic effects of both fasting and drinking alcohol
      during lactation. These findings add to the growing literature that lactating
      women metabolize alcohol differently, in part, due to the frequent breast
      stimulation during breastfeeding and the pronounced physiological changes that
      accompany one of the most energetically costly mammalian activities.

PMID- 20056374
TI  - The Birmingham hip resurfacing prosthesis: an independent single surgeon's
      experience at 7-year follow-up.
AB  - An independent single surgeon's 7-year experience with Birmingham hip resurfacing
      is presented. The study also involved investigation of the significance of
      pedestal sign in patients requiring revision. A consecutive 117 hips in 101
      patients (59 male and 42 female patients) operated on by the senior author (VGJ)
      were assessed at a mean follow-up of 7 years (range, 5-9.4 years). Mean age at
      surgery was 54 years (range, 20-74 years). Seventy-three hips had a preoperative
      diagnosis of primary osteoarthritis, and secondary osteoarthritis was seen in 44
      hips. Failure was defined as revision for any reason. Revision of the femoral
      component alone was undertaken in 8 hips (6.8%): 5 within first year for
      periprosthetic fracture neck of femur and in 3 hips after 5 years of follow-up.
      In 2 patients who were known to have osteonecrosis of the femoral head
      preoperatively, the femoral component progressively collapsed into varus after 5
      years of follow-up. Pedestal sign was the earliest radiologic sign noted in these
      2 patients and progressed rapidly within 1 year on serial radiographs well before
      the onset of clinical symptoms. Kaplan-Meier survival with revision as end point
      at 7 years was 91.5% (95% confidence interval, 97.6%-85.4%).

PMID- 20056375
TI  - Long-term outcomes of patellofemoral arthroplasty.
AB  - The purpose of this study was to correlate the long-term survival of
      patellofemoral arthroplasty with primary diagnosis, age, sex, and body mass
      index. One hundred eighty-five consecutive Richards type II patellofemoral
      arthroplasties were performed in 161 patients with isolated patellofemoral
      osteoarthritis. Diagnoses included primary patellofemoral osteoarthritis,
      posttraumatic patellofemoral osteoarthritis, and patellofemoral osteoarthritis
      with a previous realignment procedure for patellar subluxation or trochlear
      dysplasia. Median time to follow-up was 13.3 (range, 2.0-30.6) years.
      Patellofemoral arthroplasty survival was 84% at 10 years and 69% at 20 years.
      Primary diagnosis, sex, or age at patellofemoral arthroplasty did not
      significantly affect the rate of revision (P=.35, P=.24, and P=.65,
      respectively). The rate of revision in obese patients (body mass index>30 kg/m2)
      was higher than that in nonobese patients (P=.02).

PMID- 20056376
TI  - Predictors of functional impairment in pediatric obsessive-compulsive disorder.
AB  - The current study examined factors associated with obsessive-compulsive disorder
      (OCD) related functional impairment among 99 youth with OCD. A trained evaluator
      administered the Children's Yale-Brown Obsessive-Compulsive Scale, items
      assessing family accommodation, and a version of the Brown Assessment of Beliefs
      Scale that was modified for children. Youth completed the Child Obsessive
      Compulsive Impact Scale-Child Version, Obsessive-Compulsive Inventory-Child
      Version, Multidimensional Anxiety Scale for Children, and Children's Depression
      Inventory-Short Form. The child's parent completed the Child Obsessive-Compulsive
      Impact Scale-Parent Version. Results indicated that OCD symptom severity,
      depressive symptoms, and family accommodation were directly related to
      impairment, while insight was inversely related to functional impairment.
      Insight, family accommodation, and depressive symptoms predicted parent- and/or
      child-rated functional impairment above and beyond OCD symptom severity. Among
      symptom dimensions, contamination/cleaning and aggressive/checking symptoms were
      the only dimensions significantly associated with impairment. Assessment and
      treatment implications are discussed; specifically, we highlight how the
      variables of interest may impact clinical presentation and treatment course.

PMID- 20056377
TI  - Cognitive modifiability of children with developmental disabilities: a
      multicentre study using Feuerstein's Instrumental Enrichment--Basic program.
AB  - The study aimed at exploring the effectiveness of cognitive intervention with the
      new "Instrumental Enrichment Basic" program (IE-basic), based on Feuerstein's
      theory of structural cognitive modifiability that contends that a child's
      cognitive functioning can be significantly modified through mediated learning
      intervention. The IE-basic progam is aimed at enhancing domain-general cognitive
      functioning in a number of areas (systematic perception, self-regulation
      abilities, conceptual vocabulary, planning, decoding emotions and social
      relations) as well as transferring learnt principles to daily life domains.
      Participants were children with DCD, CP, intellectual impairment of genetic
      origin, autistic spectrum disorder, ADHD or other learning disorders, with a
      mental age of 5-7 years, from Canada, Chile, Belgium, Italy and Israel. Children
      in the experimental groups (N=104) received 27-90 h of the program during 30-45
      weeks; the comparison groups (N=72) received general occupational and sensory
      motor therapy. Analysis of the pre- to post-test gain scores demonstrated
      significant (p<0.05) advantage of experimental over comparison groups in three
      WISC-R subtests ("Similarities", "Picture Completion", "Picture Arrangement") and
      Raven Coloured Matrices. Effect sizes ranged from 0.3 to 0.52. Results suggest
      that it is possible to improve cognitive functioning of children with
      developmental disability. No advantage was found for children with specific
      aetiology. Greater cognitive gains were demonstrated by children who received the
      program in an educational context where all teachers were committed to the
      principles of mediated learning.

PMID- 20056378
TI  - Assisting people with multiple disabilities improve their computer-pointing
      efficiency with hand swing through a standard mouse.
AB  - This study evaluated whether two people with multiple disabilities would be able
      to improve their pointing performance using hand swing with a standard mouse
      through an Extended Dynamic Pointing Assistive Program (EDPAP) and a newly
      developed mouse driver (i.e., a new mouse driver replaces standard mouse driver,
      and changes a mouse into a precise two-dimensional motion detector, and
      intercepts mouse action). Initially, both participants had their baseline
      sessions. Then intervention started with the first participant. When his
      performance was consolidated, new baseline and intervention occurred with the
      second participant. Finally, both participants were exposed to maintenance phase,
      in which their pointing performance improved significantly. Data indicated that
      both participants improved their pointing efficiency with the use of EDPAP and
      remained highly successful through maintenance phase. Implications of the
      findings are discussed.

PMID- 20056379
TI  - Local matrix learning in clustering and applications for manifold visualization.
AB  - Electronic data sets are increasing rapidly with respect to both, size of the
      data sets and data resolution, i.e. dimensionality, such that adequate data
      inspection and data visualization have become central issues of data mining. In
      this article, we present an extension of classical clustering schemes by local
      matrix adaptation, which allows a better representation of data by means of
      clusters with an arbitrary spherical shape. Unlike previous proposals, the method
      is derived from a global cost function. The focus of this article is to
      demonstrate the applicability of this matrix clustering scheme to low-dimensional
      data embedding for data inspection. The proposed method is based on matrix
      learning for neural gas and manifold charting. This provides an explicit mapping
      of a given high-dimensional data space to low dimensionality. We demonstrate the
      usefulness of this method for data inspection and manifold visualization.

PMID- 20056380
TI  - Screening for falls and osteoporosis: prevention practice for the hand therapist.
AB  - Fractures of the upper extremity are considered a hallmark of underlying
      osteopenia or osteoporosis and strong predictors of subsequent fractures. Falling
      is the strongest single risk factor for fractures in older adults. Studies have
      shown that interventions to prevent falls can significantly reduce this risk
      factor. Hand therapists working with patients with an upper extremity injury from
      a fall cannot assume that screening for osteoporosis or the likelihood of falls
      has been addressed by other health care professionals. The purposes of this
      article are to 1) summarize osteoporosis and falls risk screening, 2) describe
      how fall prevention strategies can be integrated into hand therapy practice, and
      3) present evidence for federal and professional organizational support of
      prevention practice.

PMID- 20056381
TI  - The development of a quality appraisal tool for studies of diagnostic reliability
      (QAREL).
AB  - BACKGROUND AND OBJECTIVE: In systematic reviews of the reliability of diagnostic
      tests, no quality assessment tool has been used consistently. The aim of this
      study was to develop a specific quality appraisal tool for studies of diagnostic
      reliability. METHODS: Key principles for the quality of studies of diagnostic
      reliability were identified with reference to epidemiologic principles, existing
      quality appraisal checklists, and the Standards for Reporting of Diagnostic
      Accuracy (STARD) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS)
      resources. Specific items that encompassed each of the principles were developed.
      Experts in diagnostic research provided feedback on the items that were to form
      the appraisal tool. This process was iterative and continued until consensus
      among experts was reached. RESULTS: The Quality Appraisal of Reliability Studies
      (QAREL) checklist includes 11 items that explore seven principles. Items cover
      the spectrum of subjects, spectrum of examiners, examiner blinding, order effects
      of examination, suitability of the time interval among repeated measurements,
      appropriate test application and interpretation, and appropriate statistical
      analysis. CONCLUSIONS: QAREL has been developed as a specific quality appraisal
      tool for studies of diagnostic reliability. The reliability of this tool in
      different contexts needs to be evaluated.

PMID- 20056382
TI  - Systematic reviews on tobacco control from Cochrane and the Community Guide:
      different methods, similar findings.
AB  - OBJECTIVES: To compare the methods and findings of systematic reviews (SRs) on
      common tobacco control interventions from two organizations: the Cochrane
      Collaboration ("Cochrane") and the US Task Force for Community Preventive
      Services ("the Guide"). STUDY DESIGN AND SETTING: Literature review. We retrieved
      all reviews pertaining to tobacco control produced by the Cochrane and the Guide.
      We identified seven common topics and compared methods and findings of the
      retrieved reviews. RESULTS: There was considerable variability in the designs of
      included studies and methods of data synthesis. On average, Cochrane identified
      more studies than did the Guide (Mean 43.7 vs. 19.0), with only limited overlap
      between sets of included studies. Most Cochrane reviews (71.4%) were synthesized
      narratively, whereas most Guide reviews (85.7%) were synthesized using a median
      of effect size. Despite these differences, findings of the reviews yielded
      substantial agreement. CONCLUSION: Cochrane and the Guide conduct SRs on similar
      tobacco control-related topics differently. The SRs of the two organizations
      include overlapping, but nonidentical sets, of studies. Still, they usually reach
      similar conclusions. Identification of all pertinent original studies seems to be
      a weak point in the SR process. Policy makers should use reviews from both
      organizations in formulating tobacco control policy.

PMID- 20056383
TI  - Effect of family history on the risk of varicose veins is affected by
      differential misclassification.
AB  - OBJECTIVE: We assessed differential misclassification in self-reported family
      history of varicose veins by comparing consistency of subject's own varicose vein
      status and the consistency of information on varicose veins in family members.
      STUDY DESIGN AND SETTING: A population-based cohort study of 4,903 middle-aged
      residents of the city of Tampere, Finland. A questionnaire was used at entry and
      at the end of the 5-year follow-up. RESULTS: The estimated prevalence of positive
      family history of varicose veins varied depending on subject's own varicose veins
      from odds ratio (OR) 0.14 (95% confidence interval [CI]=0.01-0.58), in those with
      varicose veins reported in the first but not the second survey to OR 6.0 (95%
      CI=2.0-47.8), in those with varicose veins reported in the second survey but not
      in the first. The incidence of varicose veins varied from 0.4 (95% CI=0.1-1.4) to
      4.1 (95% CI=2.1-7.1) (per 100 person-years) depending how the proband memorized
      the family history. CONCLUSION: Results on the effect of family history on
      varicose veins are subject to bias, which reduces the credibility of the reports
      proposing a strong hereditary component of varicose veins.

PMID- 20056384
TI  - A nonparametric two-sample comparison for skewed data with unequal variances.

PMID- 20056385
TI  - Global Perceived Effect scales provided reliable assessments of health transition
      in people with musculoskeletal disorders, but ratings are strongly influenced by
      current status.
AB  - OBJECTIVE: The study investigated the test-retest reliability and construct
      validity of the Global Perceived Effect (GPE) scale in patients with
      musculoskeletal disorders. STUDY DESIGN AND SETTING: Data from seven clinical
      studies including 861 subjects were used for the analyses. Repeat measures taken
      at the same attendance and from attendances separated by 24 hours were compared
      to estimate test-retest reliability. Construct validity was evaluated by
      examining relationships between pre, post, and change scores in pain and
      disability measures with GPE measures. RESULTS: Intraclass correlation
      coefficient values of 0.90-0.99 indicate excellent reproducibility of the GPE
      scale. In all but one data set, change scores on pain and disability measures
      correlated well (r=0.40-0.74) with GPE; however, post scores nearly always
      correlated even more strongly (r=0.58-0.84), and pre scores showed much weaker
      association (r=0.00-0.28). Pre scores accounted for only a small amount of
      additional R(2) when added to regression models including post score.
      CONCLUSIONS: Test-retest reliability of the GPE is excellent. GPE ratings are
      strongly influenced by current status, with the effect more obvious as transition
      time lengthens. This result questions whether transition ratings truly reflect
      change, or rather just current state. This finding also has implications for the
      use of GPE ratings as an external criterion of change in clinimetric studies.

PMID- 20056386
TI  - Opening up the "Black Box": metabolic phenotyping and metabolome-wide association
      studies in epidemiology.
AB  - BACKGROUND: Metabolic phenotyping of humans allows information to be captured on
      the interactions between dietary, xenobiotic, other lifestyle and environmental
      exposures, and genetic variation, which together influence the balance between
      health and disease risks at both individual and population levels. OBJECTIVES: We
      describe here the main procedures in large-scale metabolic phenotyping and their
      application to metabolome-wide association (MWA) studies. METHODS: By use of high
      throughput technologies and advanced spectroscopic methods, application of
      metabolic profiling to large-scale epidemiologic sample collections, including
      metabolome-wide association (MWA) studies for biomarker discovery and
      identification. DISCUSSION: Metabolic profiling at epidemiologic scale requires
      optimization of experimental protocol to maximize reproducibility, sensitivity,
      and quantitative reliability, and to reduce analytical drift. Customized
      multivariate statistical modeling approaches are needed for effective data
      visualization and biomarker discovery with control for false-positive
      associations since 100s or 1,000s of complex metabolic spectra are being
      processed. CONCLUSION: Metabolic profiling is an exciting addition to the
      armamentarium of the epidemiologist for the discovery of new disease-risk
      biomarkers and diagnostics, and to provide novel insights into etiology,
      biological mechanisms, and pathways.

PMID- 20056387
TI  - Disability, more than multimorbidity, was predictive of mortality among older
      persons aged 80 years and older.
AB  - OBJECTIVE: In this study, we evaluate the impact of disability and multimorbidity
      on the risk of all-cause death in a population of frail older persons living in
      community. STUDY DESIGN AND SETTING: We analyzed data from the Aging and
      Longevity Study in the Sirente geographic area, a prospective cohort study that
      collected data on all subjects aged 80 years and older (n=364). The main outcome
      measure was all-cause mortality over 4-year follow-up. RESULTS: A total of 150
      deaths occurred. Sixty-seven subjects (44.6%) died in the nondisabled group
      compared with 83 subjects (55.3%) in the disabled group (P<0.01). Thirty-nine
      subjects (31.7%) died among subjects without multimorbidity compared with 111
      subjects (46.0%) with two or more diseases (P<0.01). When examining the combined
      effect of multimorbidity and disability, the effect of disability on the risk of
      death was higher than that of multimorbidity. After adjusting for potential
      confounders, relative to those without disability and multimorbidity, disabled
      subjects showed an increased risk of death when multimorbidity was associated
      (hazard ratio [HR]=3.91; 95% confidence interval [CI]=1.53-10.00) and in absence
      of multimorbidity (HR=2.36; 95% CI=0.63-8.83). CONCLUSION: Our results show that
      disability exerts an important influence on mortality, independently of age and
      other clinical and functional variables.

PMID- 20056388
TI  - A nonparametric two-sample comparison for skewed data with unequal variances.
AB  - OBJECTIVE: The aim of the study was to recommend a statistical test for the
      situation in which unequal variances are accompanied by skewed distributions. A
      previous publication in this journal could not recommend any test; instead,
      transformations were suggested. STUDY DESIGN AND SETTING: A recently introduced
      generalized Wilcoxon test is presented, which can be applied when variances may
      be unequal and the distribution may be skewed. This test examines the null
      hypothesis that the relative effect is 0.5. Its type I error rate was
      investigated in a simulation study. RESULTS: The generalized Wilcoxon test was
      already recommended for various areas of life sciences and, very recently, it was
      shown that a permutation test could be performed with the generalized test
      statistic. Simulation results indicate an acceptable control of the type I error
      rate even for extreme variance ratios. CONCLUSION: The generalized Wilcoxon test
      should be applied when it cannot be assumed that variances are equal and that the
      distribution is symmetric. This test is preferable to a transformation, because
      the use of transformations can be problematic, in particular when sample sizes
      are small.

PMID- 20056389
TI  - Response to letter: on the validity of meta-analysis.

PMID- 20056390
TI  - Obstructive sleep apnea in children with syndromic craniosynostosis: long-term
      respiratory outcome of midface advancement.
AB  - Almost 50% of patients with Apert, Crouzon or Pfeiffer syndrome develop
      obstructive sleep apnea (OSA), mainly due to midface hypoplasia. Midface
      advancement is often the treatment of choice, but the few papers on long-term
      outcome report mixed results. This paper aimed to assess the long-term
      respiratory outcome of midface advancement in syndromic craniosynostosis with OSA
      and to determine factors contributing to its efficacy. A retrospective study was
      performed on 11 patients with moderate or severe OSA, requiring oxygen,
      continuous positive airway pressure (CPAP), or tracheostomy. Clinical symptoms,
      results of polysomnography, endoscopy and digital volume measurement of the upper
      airways on CT scan before and after midface advancement were reviewed. Midface
      advancement had a good respiratory outcome in the short term in 6 patients and
      was ineffective in 5. In all patients without respiratory effect or with relapse,
      endoscopy showed obstruction of the rhino- or hypopharynx. The volume
      measurements supported the clinical and endoscopic outcome. Despite midface
      advancement, long-term dependence on, or indication for, CPAP or tracheostomy was
      maintained in 5 of 11 patients. Pharyngeal collapse appeared to play a role in
      OSA. Endoscopy before midface advancement is recommended to identify airway
      obstruction that may interfere with respiratory improvement after midface
      advancement.

PMID- 20056391
TI  - Cognitive remediation therapy in schizophrenia: cost-effectiveness analysis.
AB  - PURPOSE: There is a lack of evidence on the cost-effectiveness of cognitive
      remediation therapy (CRT). METHODS: Randomised controlled trial comparing usual
      care plus CRT with usual care alone. Participants had a diagnosis of
      schizophrenia and cognitive and social functioning difficulties. Health/social
      care and societal costs were estimated at 14 weeks (time 2) and 40 weeks (time 3)
      after randomisation. The outcome, proportion of participants improving their
      working memory since baseline, was combined with costs to explore cost
      effectiveness. RESULTS: 85 participants were recruited. There were no differences
      in total health/social care or societal costs between the two groups at either
      time 2 or time 3. An additional 21% of participants in the CRT group improved
      their working memory at both follow-ups. When placing these cost and outcomes in
      hypothetical scenarios concerning how much policy-makers would pay for another 1%
      of participants improving their working memory, there was more than an 80% chance
      that CRT would be cost-effective compared to usual care; at time 3, the
      likelihood of cost-effectiveness peaked at 30% even for investments up to pound
      5000. CONCLUSIONS: CRT can improve memory among people with schizophrenia and
      cognitive deficits at no additional cost. Although cost-effective in the short
      term, CRT may have limited potential to save costs in the medium term because it
      could increase take up of services. This could confer important longer term
      benefits for the patient group examined here, in terms of improved social
      functioning and less reliance on services. This can only be ascertained through
      longer follow-up.

PMID- 20056392
TI  - The synthetic cannabinoid Spice as a trigger for an acute exacerbation of
      cannabis induced recurrent psychotic episodes.

PMID- 20056393
TI  - Attenuated positive symptoms of psychosis in adolescents with chromosome 22q11.2
      deletion syndrome.
AB  - Thirty percent of individuals with chromosome 22q11.2 deletion syndrome
      (22q11.2DS) develop a psychotic disorder, particularly schizophrenia. We assessed
      attenuated positive, negative and disorganized symptoms of psychosis and clinical
      high-risk syndromes in 20 adolescents with 22q11.2DS (median age 15.1 years)
      using the Structured Interview for Prodromal Symptoms (SIPS). Two participants
      met criteria for the Attenuated Positive Symptom Syndrome, while nine
      participants (45%) experienced positive symptoms rated in the "moderate" to
      "severe and psychotic" range on the SIPS. Almost all presented with moderate to
      severe symptoms in the negative, disorganized, and general symptom domains.

PMID- 20056394
TI  - White matter abnormalities in first-episode schizophrenia: a combined structural
      MRI and DTI study.
AB  - This study examined white matter volume change and integrity jointly in patients
      with first-episode schizophrenia using an empirically derived region of interest
      approach and novel Diffusion Tensor Imaging (DTI) geometric indices. Structural
      images from 103 individuals comprising of 39 patients with first-episode
      schizophrenia and 64 healthy controls were examined for regions of white matter
      volume change using voxel-based morphometry (VBM). These regions were then
      further interrogated for group differences employing geometric indices in
      addition to fractional anisotropy (FA).VBM analyses revealed that patients with
      first-episode schizophrenia had lower white matter volume in the right temporal
      occipital region (p<0.005) corresponding to the inferior longitudinal fasciculus.
      Further analyses of diffusion anisotropy in the right temporal-occipital region
      revealed lower planar anisotropy, and higher linear anisotropy (p=0.012) in
      patients. FA in the implicated region was also found to be correlated with
      severity of delusions (r=0.47, p=0.004).We confirmed previous findings of lower
      white matter volume in the region of inferior longitudinal fasciculus. The
      presence of changes in geometric diffusion indices in the implicated white matter
      region suggested that pathophysiological processes which underlie cerebral white
      matter volume reduction may not be reflected by changes in FA. Further research
      is needed to better understand the nature of these white matter changes and its
      progression in schizophrenia over time.

PMID- 20056395
TI  - Multiple quadrupolar spin echoes in the La-filled skutterudite LaOs4As12.
AB  - We report experimental results of 139La pulse NMR studies in LaOs4As12.
      Measurements have been performed on a powder sample obtained from high quality
      single crystals. For the first time the pattern of quadrupole echoes for 139La
      nuclei (I=7/2) was obtained. All the allowed quadrupolar echoes expected for spin
      I=7/2 were observed at times t=(4/3)tau, (3/2)tau, (5/3)tau, 2tau, (5/2)tau,
      3tau, 4tau. The presence of quadrupolar echoes is the fingerprint of the
      deviation from perfect cubic symmetry of the structure and can be used as a
      simple and fast test of the sample quality.

PMID- 20056396
TI  - Measurement of delta(1)J((199)Hg, (31)P) in [HgPCy3(OAc)2]2 and relativistic ZORA
      DFT investigations of mercury-phosphorus coupling tensors.
AB  - Using 31P solid-state NMR spectroscopy, anisotropy in the indirect 199Hg-31P spin
      spin coupling tensor (DeltaJ) for powdered [HgPCy3(OAc)2]2 (1) has been measured
      as 4700 +/- 300 Hz. Zeroth-order regular approximation (ZORA) density functional
      theory (DFT) calculations, including scalar and spin-orbit relativistic effects,
      performed on 1 and a series of other related compounds show that DeltaJ(199Hg,
      (31)P) arises entirely from the ZORA Fermi-contact-spin-dipolar cross term. The
      calculations validate assumptions made in the spectral analysis of 1 and in
      previous determinations of DeltaJ in powder samples, namely that J is axially
      symmetric and shares its principal axis system with the direct dipolar coupling
      tensor (D). Agreement between experiment and theory for various 199Hg, 31P spin
      spin coupling anisotropies is reasonable; however, experimental values of
      1J(199Hg, 31P)(iso) are significantly underestimated by the calculations. The
      most important improvements in the agreement were obtained as a result of
      including more of the crystal lattice in the model used for the calculations,
      e.g., a change of 43% was noted for 1J(199Hg, 31P)(iso) in [HgPPh3(NO3)2]2
      depending on whether the two or three nearest nitrate ions are included in the
      model. Finally, we have written a computer program to simulate the effects of non
      axial symmetry in J and of non-coincidence of the J and D on powder NMR spectra.
      Simulations clearly show that both of these effects have a pronounced impact on
      the 31P NMR spectrum of 199Hg-31P spin pairs, suggesting that the effects should
      be observable experimentally if a suitable compound can be identified.

PMID- 20056397
TI  - Influence of vitamin C supplementation on lead-induced histopathological
      alterations in male rats.
AB  - This study is intended to evaluate the efficacy of vitamin C (VC) in ameliorating
      the detrimental effects of long-term lead intoxication on the liver, kidneys,
      brain and testes as assessed by histopathology. A total of forty male Wistar rats
      (six-weeks-old) was divided into 4 groups: control group; lead-acetate (PbAc)
      treated group (20 mgPbAc/kgbwt); PbAc+VC-treated group (20 mgPbAc/kgbwt plus 20
      mg VC/kgbwt); and VC-treated group (20 mgVC/kgbwt). The Experimental period was
      lasted for 60 successive days in which PbAc was administered once daily while VC
      was supplemented every other day using intra-gastric intubation. At the end of
      the experimental period, all rats were sacrificed and pathological examinations
      were performed. Control and VC-supplemented rats showed normal liver, kidney,
      brain, and testes histology. In contrast, the liver of PbAc-intoxicated rats
      exhibited degenerated hepatocytes and portal inflammatory cell infiltrations. The
      kidneys showed degenerated glomeruli and formation of karyomegalic cells
      containing intranuclear inclusions in the proximal tubular epithelium. Cerebellar
      edema, cerebral satellitosis and encephalomalacia observed in the brain.
      Testicular tissues showed arrest of spermatogenesis and interstitial edema. Co
      administration of VC with PbAc diminished the severity of pathological changes
      and reduced the number of affected organs compared to PbAc-intoxicated rats.
      These results show that low level of VC ameliorated and mitigated the adverse
      pathological impacts of chronic lead toxicity.

PMID- 20056398
TI  - Targeting cancer cells through autophagy for anticancer therapy.
AB  - Autophagy is a cellular degradation process in which portions of the cell's
      cytoplasm and organelles are sequestered in a double-membrane bound vesicle
      called an autophagosome. Fusion of autophagosomes with lysosomes results in the
      formation of autolysosomes, where the proteins and organelles are degraded. This
      degradation pathway is induced under nutrient deprivation, metabolic stress or
      microenvironmental conditions to ensure energy balance, clearance of damaged
      proteins and adaptation to stress. Disruption of autophagy is involved in diverse
      human diseases including cancer. In particular, the regulation of autophagy in
      cancer cells is complex since it can enhance tumor cell survival in response to
      certain stresses, yet it can also act to suppress the initiation of tumor growth.
      Understanding the signaling pathways involved in the regulation of autophagy as
      well as the autophagy process itself represents new directions in the development
      of anticancer therapies. In this review, we discuss recent advances in our
      understanding the complexity of the autophagy process and the development of
      targeted therapies that modulate autophagy in cancer cells in the clinic.

PMID- 20056399
TI  - The role of the Atg1/ULK1 complex in autophagy regulation.
AB  - The Atg1/ULK complex plays an essential role in the initiation of autophagy:
      receiving signals of cellular nutrient status, recruiting downstream Atg proteins
      to the autophagosome formation site, and governing autophagosome formation.
      Recent studies of mammalian Atg1 homologs (ULK1 and ULK2) have identified several
      novel interacting proteins, FIP200, mAtg13, and Atg101. FIP200 and Atg101 are not
      conserved in Saccharomyces cerevisiae, despite the high conservation rates of
      other downstream Atg proteins between the yeast and mammals. Furthermore, through
      studies of the Atg1/ULK1 complex, the molecular mechanism by which (m)TORC1
      regulates autophagy is now being clarified in detail.

PMID- 20056400
TI  - Role of autophagy in suppression of inflammation and cancer.
AB  - Autophagy is a crucial component of the cellular stress adaptation response that
      maintains mammalian homeostasis. Autophagy protects against neurodegenerative and
      inflammatory conditions, aging, and cancer. This is accomplished by the
      degradation and intracellular recycling of cellular components to maintain energy
      metabolism and by damage mitigation through the elimination of damaged proteins
      and organelles. How autophagy modulates oncogenesis is gradually emerging. Tumor
      cells induce autophagy in response to metabolic stress to promote survival,
      suggesting deployment of therapeutic strategies to block autophagy for cancer
      therapy. By contrast, defects in autophagy lead to cell death, chronic
      inflammation, and genetic instability. Thus, stimulating autophagy may be a
      powerful approach for chemoprevention. Analogous to infection or toxins that
      create persistent tissue damage and chronic inflammation that increases the
      incidence of cancer, defective autophagy represents a cell-intrinsic mechanism to
      create the damaging, inflammatory environment that predisposes to cancer. Thus,
      cellular damage mitigation through autophagy is a novel mechanism of tumor
      suppression.

PMID- 20056401
TI  - Clean Olympians? Doping and anti-doping: the views of talented young British
      athletes.
AB  - BACKGROUND: Review articles suggest a small but significant proportion (between 3
      and 12%) of male adolescents have used anabolic-androgenic steroids (AAS) at some
      point (Yesalis and Bahrke, 2000; Calfee and Fadale, 2006). In sport, the use of
      prohibited substances or processes to enhance performance, collectively referred
      to as 'doping', is banned by both sports' National and International Governing
      Bodies, and by the World Anti-Doping Agency (WADA) who run an extensive testing
      programme and educational initiatives designed to foster anti-doping attitudes.
      METHOD: A total of 40 talented male and female athletes (mean average age 19.6
      years) from 13 different sports attended 12 focus groups held over the UK
      intended to investigate athletes' attitudes toward doping. Focus group
      transcriptions were analysed and coded with the use of QSR NVivo 8. RESULTS:
      Athletes in general did not report a significant national doping problem in their
      sport, but exhibited sporting xenophobia with regard to both doping practices and
      the stringency of testing procedures outside of the UK. Athletes often viewed
      doping as 'unnatural' and considered the shame associated with doping to be a
      significant deterrent. Athletes perceived no external pressure to use performance
      enhancing drugs. In response to hypothetical questions, however, various factors
      were acknowledged as potential 'pressure' points: most notably injury recovery
      and the economic pressures of elite sport. Finally, a significant minority of
      athletes entertained the possibility of taking a banned hypothetical performance
      enhancing drug under conditions of guaranteed success and undetectability.
      CONCLUSIONS: The athletes in this study generally embraced those values promoted
      in anti-doping educational programmes, although there were some notable
      exceptions. That the social emotion of shame was considered a significant
      deterrent suggests anti-doping efforts that cultivate a shared sense of
      responsibility to remain 'clean' and emphasise the social sanctions associated
      with being deemed a 'drugs cheat', resonate with this atypical social group.

PMID- 20056402
TI  - Novel polymeric bionanocomposites with catalytic Pt nanoparticles label
      immobilized for high performance amperometric immunoassay.
AB  - We report on the aqueous preparation of novel polymeric bionanocomposites (PBNCs)
      with polydopamine (PDA) as an efficient matrix to support antibody and uniformly
      dispersed abundant Pt nanoparticles (PtNPs) for high performance sandwich-type
      amperometric immunoassay. We prepare three kinds of PBNCs (PBNCs 1, 2, and 3) via
      chemical polymerization synthesis (1) and further adsorption (2) or glutaldehyde
      (GA) covalent crosslinking (3) of antibody. Transmission electron microscopy,
      atomic force microscopy, and quartz crystal microbalance are used to characterize
      the PBNCs. The results show that PDA is an excellent matrix to support antibody
      and PtNPs due to its high biocompatibility, adsorbability, and processibility,
      and the thus-prepared PBNCs are of high immuno-recognition efficiency and high
      catalytic activity toward H(2)O(2) reduction. Then, we examine the applicability
      of the prepared PBNCs for sandwich-type amperometric immunosensing using a model
      immuno-pair of human immunoglobulin G (hIgG) and anti-hIgG, and obtain the signal
      by detecting the electro-reduction of H(2)O(2) catalyzed by the PtNPs label. The
      constructed immunosensors using PBNCs 1, 2 and 3 exhibit detection limits of
      0.068, 0.037, and 0.018 ng mL(-1), respectively, being competitive with or better
      than the reported analogues. Our immunosensors also present good reproducibility,
      stability, regeneration ability, specificity, and satisfactory feasibility for
      target assay in clinical human serum samples. The suggested protocol for the
      preparation of PBNCs with high signal-transduction ability is expected to find
      wide bioassay applications.

PMID- 20056403
TI  - Membraneless enzymatic biofuel cells based on graphene nanosheets.
AB  - The possibility of employing graphene sheets as a potential candidate for the
      construction of biofuel cells is reported in this paper. Initially, graphene
      sheets were chemically synthesized and characterized by surface characterization
      techniques. Following this, graphene was employed to fabricate the anode and
      cathode in the biofuel cell. The anode of the biofuel cell consists of a gold
      electrode on which we co-immobilized graphene - glucose oxidase using silica sol
      gel matrix. Voltammetric measurements were conducted to quantitatively evaluate
      the suitability of employing graphene sheets as an electrode dopant and its
      performance was compared with single walled carbon nanotubes (SWCNTs). The
      cathode of the biofuel cell was constructed in a similar method except that
      graphene was co-immobilized with bilirubin oxidase. Finally, two membraneless
      enzymatic biofuel cells, one using graphene sheets and the other using SWCNTs,
      were constructed and their performances were compared. Upon comparison, graphene
      based biofuel cell exhibited a maximum power density of about 24.3+/-4 microW
      (N=3), which is nearly two times greater than that of the SWCNTs biofuel cell,
      and the performance of the graphene biofuel cell lasted for 7 days.

PMID- 20056404
TI  - An innovative reactor-type biosensor for BOD rapid measurement.
AB  - Biochemical oxygen demand (BOD) is one of the most important and widely used
      parameters for characterizing the organic pollution of water and wastewater. In
      this paper, a novel reactor-type biosensor for rapid measurement of BOD was
      developed, based on using immobilized microbial cell (IMC) beads as recognition
      bio-element in a completely mixed reactor which was used as determining chamber,
      replacing the traditionally used membrane as recognition bio-element. The IMC
      beads were freely suspended in the aqueous solution, so the mass transfer
      resistance for dissolved oxygen and organic compounds significantly reduced, and
      the quantity of the microbial cells used as recognition element can be easily
      adjusted, in comparison with the traditional membrane-type BOD biosensor, in
      which exists a unadjustable contradiction between the quantity of biomass and the
      thickness of the bio-membrane, thus limiting the stability and the detection
      limit. This novel kind of BOD biosensor significantly increased the sensitivity
      of the response, the detecting precision and prolonged the life time of the
      recognition element. The experimental data showed that the most appropriate
      temperature for biochemical reaction in the reactor was 30 degrees C, and the IMC
      beads could keep the bioactivity for about 70d at the detecting frequency of 8
      times every day. The standard deviation of repeatability and the reproducibility
      of responses were within +/-6.4% and +/-5.0%, respectively, which are within
      acceptable bias limits, and meet the requirement of BOD rapid measurement.

PMID- 20056405
TI  - A colorimetric strategy based on a water-soluble conjugated polymer for sensing
      pH-driven conformational conversion of DNA i-motif structure.
AB  - Using a water-soluble conjugated polymer (CP) as a sensing probe, we developed a
      rapid colorimetric detection strategy for pH-driven conformational conversion of
      DNA i-motif structure. Two sensing configurations were designed: one used CP only
      to detect the conversion between i-motif and random-coiled state of a C-rich
      single-strand DNA, the other used CP and a complementary single-strand DNA to
      investigate the conversion of duplex to i-motif equilibrium. All the conversions
      would lead to color change observed directly with naked eyes within a few
      minutes. The limitation of detection (LOD) is as low as 40 nM. More importantly,
      reversible conformational conversions by adjusting the pH of the system could
      also be detected.

PMID- 20056406
TI  - Neuropathic pain and its assessment.
AB  - Neuropathic pain, i.e., pain arising as a direct consequence of a lesion or
      disease affecting the somatosensory system, is a frequent complaint in the
      elderly. The frequency of herpes zoster and peripheral neuropathy, the commonest
      diseases that cause neuropathic pain, increases with age. More than half of all
      persons in whom herpes zoster develops are older than 60 years and about 30% of
      these patients will ultimately suffer from chronic postherpetic neuralgia. The
      prevalence of peripheral neuropathy rises from 2.4% in the general population to
      8% in subjects older than 55 years. With advancing age, the nociceptive pathway
      undergoes degenerative changes, mainly consisting of axonal loss. This age
      related nociceptive pathway degeneration probably explains why elderly patients
      tend to under-report pain in many medical conditions including myocardial
      infarction, fractures, and arthritis. This age-related impairment probably plays
      a key role in the development of neuropathic pain. In this report we describe the
      most reliable methods for assessing neuropathic pain such as laser evoked
      potential (LEP) recordings and skin biopsy, procedures that selectively assess
      nociceptive pathways in order to obtain a rapid diagnosis and hence determine
      treatment.

PMID- 20056407
TI  - Optimization study of ethanolic fermentation from oil palm trunk, rubberwood and
      mixed hardwood hydrolysates using Saccharomyces cerevisiae.
AB  - Ethanolic fermentation using Saccharomyces cerevisiae was carried out on three
      types of hydrolysates produced from lignocelulosic biomass which are commonly
      found in Malaysia such as oil palm trunk, rubberwood and mixed hardwood. The
      effect of fermentation temperature and pH of hydrolysate was evaluated to
      optimize the fermentation efficiency which defined as maximum ethanol yield in
      minimum fermentation time. The fermentation process using different temperature
      of 25 degrees Celsius, 30 degrees Celsius and 40 degrees Celsius were performed
      on the prepared fermentation medium adjusted to pH 4, pH 6 and pH 7,
      respectively. Results showed that the fermentation time was significantly reduced
      with the increase of temperature but an adverse reduction in ethanol yield was
      observed using temperature of 40 degrees Celsius. As the pH of hydrolysate became
      more acidic, the ethanol yield increased. Optimum fermentation efficiency for
      ethanolic fermentation of lignocellulosic hydrolysates using S. cerevisiae can be
      obtained using 33.2 degrees Celsius and pH 5.3.

PMID- 20056408
TI  - Agar extraction from integrated multitrophic aquacultured Gracilaria
      vermiculophylla: evaluation of a microwave-assisted process using response
      surface methodology.
AB  - Microwave-assisted extraction (MAE) of agar from Gracilaria vermiculophylla,
      produced in an integrated multitrophic aquaculture (IMTA) system, from Ria de
      Aveiro (northwestern Portugal), was tested and optimized using response surface
      methodology. The influence of the MAE operational parameters (extraction time,
      temperature, solvent volume and stirring speed) on the physical and chemical
      properties of agar (yield, gel strength, gelling and melting temperatures, as
      well as, sulphate and 3,6-anhydro-L-galactose contents) was evaluated in a 2(4)
      orthogonal composite design. The quality of the extracted agar compared favorably
      with the attained using traditional extraction (2 h at 85 degrees Celsius) while
      reducing drastically extraction time, solvent consumption and waste disposal
      requirements. Agar MAE optimum results were: an yield of 14.4 + or - 0.4%, a gel
      strength of 1331 + or - 51 g/cm(2), 40.7 + or - 0.2 degrees Celsius gelling
      temperature, 93.1 + or - 0.5 degrees Celsius melting temperature, 1.73 + or -
      0.13% sulfate content and 39.4 + or - 0.3% 3,6-anhydro-L-galactose content.
      Furthermore, this study suggests the feasibility of the exploitation of G.
      vermiculophylla grew in IMTA systems for agar production.

PMID- 20056409
TI  - In vivo and in vitro polycyclic aromatic hydrocarbons degradation by Lentinus
      (Panus) tigrinus CBS 577.79.
AB  - The ability of stationary and shaken Lentinus tigrinus CBS 577.79 liquid cultures
      to degrade a mixture of polycyclic aromatic hydrocarbons (PAHs) in N-rich (i.e.,
      malt extract glucose, MEG) and in N-limited (low-N Kirk's medium, LNKM) media was
      investigated. Best results were obtained in shaken cultures where PAHs were
      degraded by 91% and 97% in MEG and LNKM, respectively; in stationary cultures, on
      the contrary, the degradation was never higher than 50%. Laccase activity was
      predominant on MEG while Mn-peroxidase (MnP) was preferentially produced in LNKM.
      The identification of degradation products showed the presence of several PAH
      derivatives, such as quinones, dicarboxylated and ring fission derivatives,
      presumably derived from the action of lignin-modifying enzymes. The presence of
      some degradation products (e.g., hydroxylated derivatives of anthrone and
      phenanthrene 9,10-dihydrodiol) suggested the possible involvement of cytochrome P
      450-epoxide hydrolase system, the active form of which was found in 7-day-old
      cultures on MEG. In vitro experiments showed that the MnP from L. tigrinus had
      wider PAH substrate range and higher oxidation ability than the laccase produced
      by the same strain.

PMID- 20056410
TI  - Yield performances and changes in enzyme activities of Pleurotus spp. (P.
      ostreatus and P. sajor-caju) cultivated on different agricultural wastes.
AB  - Pleurotus ostreatus and Pleurotus sajor-caju were studied for their ability to
      produce laccase and carboxymethylcellulase (CMCase) enzymes on different
      agricultural wastes under solid state fermentation. The spawns of P. ostreatus
      and P. sajor-caju were inoculated on different agricultural wastes including
      viticulture wastes, wheat straw, paddy straw, sesame straw, sawdust as well as
      the mixtures of these wastes with wheat bran. The carbon and nitrogen contents of
      substrates containing bran were the highest. The laccase activities of P.
      ostreatus and P. sajor-caju reached the highest values on the day 10 of mycelial
      growth. This enzyme activity was higher on the substrates containing bran which
      had high nitrogen and low C/N ratio than the other tested substrates with no
      bran. The CMCase activities of P. sajor-caju and P. ostreatus had two peaks on
      the 5th day of mycelial growth and after first flash. P. ostreatus and P. sajor
      caju grown on substrates containing wheat bran had higher biological efficiencies
      and total yields as well as higher CMCase and laccase activities.

PMID- 20056411
TI  - Comparison of nitrogen removal and microbial distribution in wastewater treatment
      process under different electron donor conditions.
AB  - The applicability of modified spent caustic (MSC) as an electron donor for
      denitrification was evaluated in a lab-scale reactor for the Bardenpho process
      under various electron donor conditions: (A) no electron donor, (B) methanol, (C)
      thiosulfate and (D) MSC conditions. TN removal efficiency varied in each
      condition, 23.1%, 87.8%, 83.7% and 71.7%, respectively. The distribution ratio of
      nitrifying bacteria and DGGE profile including sulfur-reducing or oxidizing
      bacteria also varied depending on the conditions. These results indicated that
      the MSC would be used as an efficient electron donor for denitrification by
      autotrophic denitrifier in wastewater treatment process.

PMID- 20056412
TI  - Long term operation of a thermophilic anaerobic reactor: process stability and
      efficiency at decreasing sludge retention time.
AB  - The aim of this study was to evaluate the performance of thermophilic sludge
      digestion at decreasing sludge retention time (SRT) and increasing organic
      loading rate (OLR), in terms of methane production, effluent stabilisation,
      hygienisation and dewaterability. Focus was put on determining indicators to help
      prevent process failure. To this end, a lab-scale reactor was operated for nearly
      2 years at 55 degrees Celsius. Methane production rate was increased (from 0.2 to
      0.4-0.6 m(3)((ch)(4)) m(-3)(reactor) d(-1)) by decreasing the SRT from 30 to 15
      10 days, while increasing the OLR from 0.5 to 2.5-3.5 kg VS m(-3)(reactor) d(-1).
      Sludge dewaterability was worsened at SRT below 15 days; while pathogen
      destruction was always successful. The following concentrations might be used to
      prevent process failure: VFA C2-C5 (3.7 g CODL(-1)), acetate (0.6 g L(-1)),
      acetate/propionate (0.5), intermediate alkalinity (1.8 g CaCO(3) L(-1)),
      intermediate/partial alkalinity (0.9), intermediate/total alkalinity (0.5), CH(4)
      in biogas (55%).

PMID- 20056413
TI  - Exploration of composted cereal waste and poultry manure for soil restoration.
AB  - Poultry manure and fungal consortium developed by including fungi of genus
      Aspergillus, Trichoderma and Phanerochaete were evaluated separately to degrade
      high silica paddy straw. The quality evaluation of composted organic wastes after
      two months of decomposition revealed that poultry manure amended paddy straw
      compost had a C:N ratio of 13.06 and germination index of 132%, compared to 15.29
      and 114% of its fungal inoculated counterpart. Supplementation of paddy straw
      with poultry manure was as effective as its bioaugmentation with fungal
      consortium. The incorporation of poultry manure @ 3 t ha(-1) (T3) and poultry
      manure amended paddy straw compost @ 3 t ha(-1)+N(60)P(40)K(30) (T4) separately
      to soil under rice crop for two consecutive years, resulted in improved microbial
      biomass and different enzymatic activities responsible for nutrient cycling. T3
      and T4 treatments recorded a grain yield improvement of 54.87 and 79.26%
      respectively in 2007 and 79 and 80.2% respectively in 2008 compared to
      N(120)P(80)K(60).

PMID- 20056414
TI  - Biosolid and alum effects on runoff losses during turfgrass establishment.
AB  - Large, volume-based rates of composted biosolids (CB) enhance turfgrass
      establishment and soil properties, but nonpoint-source runoff losses could occur
      during production and after transplanting of sod. The objective was to evaluate
      runoff losses of N, P, sediment, and organic C during establishment of sprigs or
      transplanted sod of Tifway bermudagrass (Cynodon dactylon L. Pers. X C.
      transvaalensis Burtt-Davey) with and without CB and aluminum sulfate (Alum). Four
      treatments comprised Tifway sprigged in a sandy loam soil with and without
      incorporation of 0.25 m(3) CB m(-3) soil and Alum. In four additional treatments,
      sod transplanted from Tifway grown with and without CB was established with and
      without a surface spray of Alum. During early establishment, CB incorporated in
      soil before sprigging reduced runoff loss of sediment and total N to amounts
      comparable to transplanted sod. In contrast, mean runoff losses of total
      dissolved P and soluble-reactive P (SRP) were more than 50% greater for CB
      amended sod than for fertilizer-grown sod or Tifway sprigged in soil with or
      without CB. Yet, the surface spray of Alum reduced runoff loss from sod more than
      88% for SRP and 41% for dissolved organic C. Both surface sprays and
      incorporation of Alum effectively reduced SRP runoff loss from CB, soil, and
      turfgrass sources during turfgrass establishment.

PMID- 20056415
TI  - Characterization of lignin during oxidative and hydrothermal pre-treatment
      processes of wheat straw and corn stover.
AB  - The objective of the study was to characterize and map changes in lignin during
      hydrothermal and wet explosion pre-treatments of wheat straw and corn stover.
      Chemical composition, microscopic (atomic force microscopy and scanning electron
      microscopy) and spectroscopic (attenuated total reflectance Fourier transform
      infrared spectroscopy, ATR-FTIR) analyses were performed. Results showed that
      both pre-treatments improved the cellulose and lignin content with substantial
      removal of hemicellulose in the pre-treated biomasses. These values were slightly
      higher for hydrothermal compared to wet explosion pre-treatment. ATR-FTIR
      analyses also confirmed these results. Microscopic analysis showed that pre
      treatments affected the biomass by partial difibration. Lignin deposition on the
      surface of the hydrothermally pre-treated fibre was very distinct while severe
      loss of fibril integrity was noticed with wet exploded fibre. The present study
      thus revealed that the lignin cannot be removed by the studied pre-treatments.
      However, both pre-treatments improved the accessibility of the biomass towards
      enzymatic hydrolysis.

PMID- 20056416
TI  - Delignification of Miscanthus x Giganteus by the Milox process.
AB  - Miscanthus x giganteus stalks were subjected to delignification with formic acid
      hydrogen peroxide-water in two stages. A face-centered experimental design was
      used to study the effects of different variables (formic acid and hydrogen
      peroxide concentrations, time and temperature) on yield, lignin content and
      viscosity of pulps on the first stage. Fitting equations described satisfactorily
      the system behaviour and showed that hydrogen peroxide concentration and
      temperature were the most influencing variables. A set of independent variables
      (90% formic acid, 1.5% hydrogen peroxide, 60 min, and 67 degrees Celsius)
      produced a pulp with low lignin content (kappa 17.2) and high viscosity (899
      cm(3)/g), in the first stage. For the second stage a treatment time of 30 min was
      the more suitable, producing good quality pulps (kappa number 4.6, viscosity 788
      cm(3)/g). Phenolic hydroxyl and carboxyl group contents were higher lignins from
      the first stage.

PMID- 20056417
TI  - Effect of carbon sources on sulfidogenic bacterial communities during the
      starting-up of acidogenic sulfate-reducing bioreactors.
AB  - The effect of different carbon sources on the starting-up duration of
      sulfidogenic bioreactor and corresponding bacterial communities were
      investigated. The bioreactor starting-up duration was closely dependent on the
      complexity and availability of the carbon sources. 16S rRNA gene diversity of
      climax bacterial communities developed in each bioreactor had an increasing
      tendency for the carbon resource of lactate, acetate/ethanol, glucose and
      molasses. At the steady stage of bioreactors, the molasses-fed bacterial
      community pattern grouped with that of glucose-fed and acetate/ethanol-fed
      grouped with that of lactate-fed, both of which separated each other and departed
      further from the seed sludge. The present study concludes that utilization of
      simple carbon sources that are readily utilized by sulfate-reducing bacteria
      (SRB) can not only increase the fraction of SRB and thus improve sulfate removal
      efficiency, but also shorten the starting-up duration.

PMID- 20056418
TI  - Design and synthesis of some new quinoline-3-carbohydrazone derivatives as
      potential antimycobacterial agents.
AB  - A series of 26 new quinoline derivatives carrying active pharmacophores has been
      synthesized and evaluated for their in vitro antituberculosis activity against
      Mycobacterium tuberculosis H37Rv (MTB), Mycobacterium smegmatis (MC(2)), and
      Mycobacterium fortuitum following the broth micro dilution assay method.
      Compounds 13e, 13i, 13k, 14a, 14c, 14i, and 14k exhibited significant minimum
      inhibition concentrations, when compared with first line drugs isoniazid (INH)
      and rifampicin (RIF) and could be ideally suited for further modifications to
      obtain more efficacious compounds in the fight against multi-drug resistant
      tuberculosis.

PMID- 20056419
TI  - Variability and fluctuation in running gait cycle of trained runners and non
      runners.
AB  - The current study examined variability and fluctuation in the running gait cycle,
      focusing on differences between trained distance runners and non-runners. The two
      groups of participants performed treadmill running at 80%, 100%, and 120% of
      their preferred speed for 10 min. Stride-interval time-series were recorded
      during running using footswitches. The average preferred speed was significantly
      higher for the trained runners than for the non-runners. The trained runners
      showed significantly smaller variability of stride interval than did the non
      runners, and at the same time the scaling exponent alpha evaluated by detrended
      fluctuation analysis tended to be smaller for the trained runners. These results
      suggest that expert runners can reduce variability in the trained movement
      without loosing dynamical degrees of freedom for spatiotemporal organization of
      the gait pattern.

PMID- 20056420
TI  - Meta-analysis and use of tests of heterogeneity in neurosurgery.
AB  - The recent increase in implementation of evidence-based medicine in neurosurgery
      has led to an increase in awareness of the importance of meta-analysis. An
      integral component of meta-analysis is the test of heterogeneity. This test
      examines whether the apparent differences between the studies are significant
      enough to bias the outcome and conclusion of the meta-analysis. The author has
      examined four different tests of heterogeneity available in the scientific
      literature for binary data. In the context of neurosurgical data, the author
      found that Pearson's test was the most accurate in terms of Type I and Type II
      errors, as well as "goodness-of-fit" between the empirical distribution and
      approximate chi-squared distribution. Moreover, its ease of computation made this
      test a highly favorable test to be used in neurosurgical data analysis.

PMID- 20056421
TI  - Prognostic factors of hearing preservation after gamma knife radiosurgery for
      vestibular schwannoma.
AB  - We conducted a prospective study to identify prognostic factors of hearing
      preservation after gamma knife radiosurgery (GKRS) for vestibular schwannoma
      (VS). Twenty-seven patients with unilateral VS and serviceable hearing underwent
      GKRS. The mean lesion diameter was 17.3mm (range 6.1-30.0mm), the median marginal
      dose was 12 Gy (11-15 Gy), and the mean follow-up duration was 35.7 months (9-81
      months). The probabilities of hearing preservation after GKRS were calculated
      using the Kaplan-Meier method. Tumor growth was controlled in 26 of the 27
      patients (96.3%), and rates of hearing preservation were 85.1% and 68.1% at 2 and
      3 years, respectively. A normal auditory brainstem response (ABR) (p = 0.008) and
      Gardner-Robertson class I hearing (p = 0.012) before GKRS were found to be
      significant prognostic factors of a favorable outcome. Our findings suggest that
      a normal pre GKRS ABR strongly predicts hearing preservation after GKRS.
      Accordingly, we advise that ABR should be considered with other prognostic
      factors when GKRS is considered in patients with VS.

PMID- 20056422
TI  - Phrenic nerve stimulation: the Australian experience.
AB  - Phrenic nerve stimulation is a technique whereby a nerve stimulator provides
      electrical stimulation of the phrenic nerve to cause diaphragmatic contraction.
      The most common indications for this procedure are central alveolar
      hypoventilation and high quadriplegia. This paper reviews the available data on
      the 19 patients treated with phrenic nerve stimulation in Australia to date. Of
      the 19 patients, 14 required pacing due to quadriplegia, one had congenital
      central hypoventilation syndrome and one had brainstem encephalitis. Information
      was unavailable for the remaining three patients. Currently, 11 of the pacers are
      known to be actively implanted, with the total pacing duration ranging from 1 to
      21 years (mean 13 years). Eight of the 19 patients had revision surgeries. Four
      of these were to replace the original I-107 system (which had a 3-5-year life
      expectancy) with the current I-110 system, which is expected to perform
      electrically for the patient's lifetime. Three patients had revisions due to
      mechanical failure. The remaining patients' notes were incomplete. These data
      suggest that phrenic nerve stimulation can be used instead of mechanical
      ventilators for long-term ongoing respiratory support.

PMID- 20056423
TI  - Association between mild parkinsonian signs and mortality in an elderly male
      cohort in China.
AB  - Our study aimed to examine the predictive role of mild parkinsonian signs (MPS)
      on mortality in an elderly male cohort. From January 2004, 1759 retired male
      military officers in Nanjing, China, underwent detailed clinical evaluations,
      which included assessments of MPS using an abbreviated Unified Parkinson's
      Disease Rating Scale at baseline. Data on deaths attributed to any cause were
      collected over a 4-year period of follow-up visits. Cox proportional hazard
      regression models were used to estimate the effect of MPS and chronic diseases on
      mortality. Of the 1759 participants, 278 (15.8%) had MPS at baseline. The
      participants with MPS and those without did not differ significantly with respect
      to the prevalence of chronic illness. The multivariate-adjusted relative risk of
      death (risk ratio, RR) for MPS was 1.77. After adjustment for the other MPS
      domains and chronic illnesses, only axial function abnormality was associated
      with an increased risk of death (RR 2.07). The presence of MPS in elderly
      subjects at baseline is a significant predictor of risk, even after adjustment
      for chronic illness.

PMID- 20056424
TI  - Mevalonate analogues as substrates of enzymes in the isoprenoid biosynthetic
      pathway of Streptococcus pneumoniae.
AB  - Survival of the human pathogen Streptococcus pneumoniae requires a functional
      mevalonate pathway, which produces isopentenyl diphosphate, the essential
      building block of isoprenoids. Flux through this pathway appears to be regulated
      at the mevalonate kinase (MK) step, which is strongly feedback-inhibited by
      diphosphomevalonate (DPM), the penultimate compound in the pathway. The human
      mevalonate pathway is not regulated by DPM, making the bacterial pathway an
      attractive antibiotic target. Since DPM has poor drug characteristics, being
      highly charged, we propose to use unphosphorylated, cell-permeable prodrugs based
      on mevalonate that will be phosphorylated in turn by MK and phosphomevalonate
      kinase (PMK) to generate the active compound in situ. To test the limits of this
      approach, we synthesized a series of C(3)-substituted mevalonate analogues to
      probe the steric and electronic requirements of the MK and PMK active sites. MK
      and PMK accepted substrates with up to two additional carbons, showing a
      preference for small substituents. This result establishes the feasibility of
      using a prodrug strategy for DPM-based antibiotics in S. pneumoniae and
      identified several analogues to be tested as inhibitors of MK. Among the
      substrates accepted by both enzymes were cyclopropyl, vinyl, and ethynyl
      mevalonate analogues that, when diphosphorylated, might be mechanism-based
      inactivators of the next enzyme in the pathway, diphosphomevalonate
      decarboxylase.

PMID- 20056425
TI  - Design, synthesis and biological evaluation of chrysin long-chain derivatives as
      potential anticancer agents.
AB  - A series of long-chain derivatives of chrysin (compounds 3-22) were synthesized
      to evaluate for their antiproliferative activities against the human liver cancer
      cell line HT-29 and EGFR inhibitory activity. Among the compounds tested,
      compounds hexadecyl 2-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)acetate (10)
      and N-hexadecyl 2-(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yloxy)acetamide (20)
      displayed potent EGFR inhibitory activity with IC(50) values of 0.048 microM and
      0.035 microM), comparable to the positive control erlotinib. Docking simulation
      of compounds 10 and 20 was carried out to illustrate the binding mode of the
      molecular into the EGFR active site, and the result suggested that compound 10
      and 20 can bind the EGFR kinase well. Thus, compounds 10 and 20 with potent EGFR
      inhibitory activity would be potential anticancer agents.

PMID- 20056426
TI  - Synthesis, biological evaluation, and molecular modeling of berberine derivatives
      as potent acetylcholinesterase inhibitors.
AB  - By targeting the dual active sites of acetylcholinesterase (AChE), a new series
      of berberine derivatives was designed, synthesized, and evaluated as AChE
      inhibitors. Most of the derivatives inhibited AChE in the sub-micromolar range.
      Compound 8c, berberine linked with phenol by a 4-carbon spacer, showed the most
      potent inhibition of AChE. A kinetic study of AChE and BuChE indicated that a mix
      competitive binding mode existed for these berberine derivatives. Molecular
      modeling studies confirmed that these hybrids target both the catalytic active
      site (CAS) and the peripheral anionic site (PAS) of AChE. This is the first
      report where AChE inhibitory activity has been associated with berberine as a
      lead molecule.

PMID- 20056427
TI  - Changes in the haemocytes of Agrotis ipsilon larvae (Lepidoptera: Noctuidae) in
      relation to dimilin and Bacillus thuringiensis infections.
AB  - Five types of haemocytes are observed in the fourth larval instar of the black
      cutworm, Agrotis ipsilon: prohaemocytes (PRs), plasmatocytes (PLs), granulocytes
      (GRs), spherule cells (SPs) and adipohaemocytes (ADs). Infection of A. ipsilon
      fourth larval instar with Bacillus thuringiensis and dimilin resulted in a
      reduction of the total haemocyte count. Changes in the differential haemocyte
      population during bacterial and dimilin infections have been assessed. The PRs %
      decreased significantly while SPs, PLs, and GRs % increased significantly after
      the application of the two insecticides at 12 and 24h. Ultrastructural
      alternations and malformations have been observed in circulating haemocytes of A.
      ipsilon larvae treated with dimilin and B. thuringiensis.

PMID- 20056428
TI  - Biodistribution of phenylboric acid derivative entrapped lipiodol and 4-borono-2
      18F-fluoro-L-phenylalanine-fructose in GP7TB liver tumor bearing rats for BNCT.
AB  - A new phenylboric acid derivative entrapped lipiodol (PBAD-lipiodol) was
      developed as a boron carrier for the boron neutron capture therapy (BNCT) of
      hepatoma in Taiwan. The biodistribution of both PBAD-lipiodol and BPA-fructose
      was assayed in GP7TB hepatoma-bearing rat model. The highest uptake of PBAD
      lipiodol was found at 2h post injection. The application of BNCT for the hepatoma
      treatment in tumor-bearing rats is suggested to be 2-4h post PBAD-lipiodol
      injection.

PMID- 20056429
TI  - Monte Carlo simulation to positron emitter standardized by means of 4pibeta-gamma
      coincidence system--application to 22Na.
AB  - The present work describes the methodology for predicting the behavior of
      extrapolation curves obtained in radionuclide standardization by 4pibeta-gamma
      coincidence measurements, applied to (22)Na, developed at the Laboratorio de
      Metrologia Nuclear of IPEN-CNEN/SP (LMN-Nuclear Metrology Laboratory). The LMN
      system consists of a proportional counter (PC) in 4pi geometry coupled to a
      single or a pair of NaI(Tl) scintillation crystals. Two standardization
      techniques were used: the Sum-Peak and the Nuclear-Peak methods. The theoretical
      response functions of each detector have been calculated using the MCNPX Monte
      Carlo code. The code ESQUEMA, developed at LMN, has been used for calculating the
      extrapolation curve in the 4pibeta-gamma coincidence experiment. Modifications
      were performed in order to include response tables for positrons and coincidences
      with annihilation photons. From the calibration results it was possible to
      extract both the activity value and the positron emission probability per decay.
      The latter was compared with results from the literature.

PMID- 20056430
TI  - Radon in groundwater and dose estimation for inhabitants in Spas of the Sudety
      Mountain area, Poland.
AB  - Studies of radon isotope (222)Rn activity concentration in underground water in
      the Sudety region were performed with the use of the liquid scintillation
      technique. Waters chosen for investigations were collected in 24 health resorts
      and towns of the Sudety area from 115 springs, wells and intakes. The (222)Rn
      activity concentration varied within the range from 4.2+/-0.4 to 1703+/-55 Bq/l.
      The annual effective doses due to the consumption of (222)Rn with water were
      calculated for 50 sources of underground spring water or tap water used for
      consumption. The results were within the range from 0.003 to 1.1 mSv/yr, assuming
      0.5 l of tap water per day from which radon is not removed or 0.5 l of mineral
      spring water consumed daily. The contribution to the effective dose from the
      inhalation of radon during the daily usage of domestic water substantially
      increases its effective dose.

PMID- 20056431
TI  - Activity measurement of 85Kr diluted by a large volume balloon technique.
AB  - The National Metrology Institute of Japan (NMIJ) participated in the CCRI(II) Key
      comparison of (85)Kr activity measurement. The absolute internal gas-counting
      method was used, with a set of proportional counters of different length. The
      original (85)Kr gas was diluted by a factor of 2x10(5) in order to achieve the
      suitable activity concentration for the proportional counters. A new dilution
      method was introduced, based on a large-volume balloon and gravimetric
      determination of the dilution volume with small uncertainties.

PMID- 20056432
TI  - Proficiency testing feasibility study for the measurement of gamma-emitting
      clearance samples.
AB  - A proficiency testing feasibility study program was proposed by the National
      Radiation Standard Laboratory (NRSL) of Taiwan to understand the capabilities of
      laboratories dealing with clearance measurements, and to issue related technical
      criteria for radioactive waste assay. In this program, twelve blind test samples
      with different levels of radioactivity, radionuclides and different packing
      densities were prepared. Seven laboratories participated in this program and
      fourteen instruments were tested. Participants were required to report their raw
      data to NRSL, which would evaluate the effects of the background, geometry and
      the packing density to obtain the final results of the participants. In this
      study, the typical uncertainties of the participants were around 24%, and about
      70% of the measured results produced E(n) values, which were smaller than one.

PMID- 20056433
TI  - Managing the pneumonectomy space after extrapleural pneumonectomy: postoperative
      intrathoracic pressure monitoring.
AB  - OBJECTIVE: Rapid fluid evacuation of the pneumonectomy space can cause
      ipsilateral mediastinal shift, contralateral lung hyperexpansion, compromised
      caval blood return and a precipitous drop in cardiac output. Conversely, rapid
      fluid accumulation can cause contralateral mediastinal shift with compression of
      the remaining lung and respiratory insufficiency. In this retrospective analysis,
      we evaluate the efficacy of intrathoracic pressure monitoring and intermittent
      fluid aspiration to manage the pneumonectomy space in the early postoperative
      period following extrapleural pneumonectomy. METHODS: Prior to chest closure, a
      14 F Rob-Nel catheter was placed in the pneumonectomy space and connected to
      pressure tubing to monitor ipsilateral intrathoracic pressure continuously.
      Central venous pressure monitoring and serial chest X-rays were performed
      according to usual intensive care routine. Pneumonectomy space fluid was
      aspirated intermittently when there was increase in intrathoracic pressure,
      refractory hypotension, mediastinal shift on chest X-ray, or clinical decline.
      Postoperative imaging was re-evaluated retrospectively for confirmation of
      mediastinal shift by a senior radiologist. RESULTS: From January to December
      2008, 47 patients underwent extrapleural pneumonectomy for pleural mesothelioma
      (median age 65 years with range 34-79 years, 77% male). Twenty (43%) patients had
      left-sided disease and 32 (68%) received local heated intra-operative cisplatin
      based chemotherapy. The median baseline pneumonectomy space pressure was 3 cm
      H(2)O (range: -6 to +12). The median amount of fluid withdrawn over the first 2
      days postoperatively was 300 cc (range: 0-1980 cc). Thirty-one (69%) patients had
      minimal, if any, change in mediastinal position during the first 2 postoperative
      days with intermittent drainage performed when the pneumonectomy space pressure
      rose. Eleven (25%) patients had increasing contralateral shift, four of whom had
      return of the mediastinum to baseline during this time period. The median fluid
      drained from the four patients whose contralateral shift resolved was 290 cc
      (range: 220-800 cc) compared to 200 cc (range: 150-480 cc) from the seven
      patients whose contralateral shift remained, but this difference did not reach
      significance (p=0.365). CONCLUSIONS: Intrathoracic pressure monitoring may be
      used as a guide for intermittent fluid evacuation of the pneumonectomy space
      prior to onset of clinical signs or symptoms, to avoid the cardiopulmonary risks
      of rapid fluid removal. Contralateral mediastinal shift should be treated with
      incremental drainage when there is a rise in intrathoracic pressure to prevent
      cardiovascular complications.

PMID- 20056434
TI  - Evolution of adaptive immune recognition in jawless vertebrates.
AB  - All extant vertebrates possess an adaptive immune system wherein diverse immune
      receptors are created and deployed in specialized blood cell lineages. Recent
      advances in DNA sequencing and developmental resources for basal vertebrates have
      facilitated numerous comparative analyses that have shed new light on the
      molecular and cellular bases of immune defense and the mechanisms of immune
      receptor diversification in the "jawless" vertebrates. With data from these key
      species in hand, it is becoming possible to infer some general aspects of the
      early evolution of vertebrate adaptive immunity. All jawed vertebrates assemble
      their antigen-receptor genes through combinatorial recombination of different
      "diversity" segments into immunoglobulin or T-cell receptor genes. However, the
      jawless vertebrates employ an analogous, but independently derived set of immune
      receptors in order to recognize and bind antigens: the variable lymphocyte
      receptors (VLRs). The means by which this locus generates receptor diversity and
      achieves antigen specificity is of considerable interest because these mechanisms
      represent a completely independent strategy for building a large immune
      repertoire. Therefore, studies of the VLR system are providing insight into the
      fundamental principles and evolutionary potential of adaptive immune recognition
      systems. Here we review and synthesize the wealth of data that have been
      generated towards understanding the evolution of the adaptive immune system in
      the jawless vertebrates.

PMID- 20056435
TI  - Association of paternal age and risk for major congenital anomalies from the
      National Birth Defects Prevention Study, 1997 to 2004.
AB  - PURPOSE: The objective of this study was to examine the associations between
      paternal age and birth defects of unknown etiologies while carefully controlling
      for maternal age. METHODS: By using 1997 to 2004 data from the National Birth
      Defects Prevention Study, we fit logistic regression models with paternal and
      maternal age as continuous variables while adjusting for demographic and other
      factors. RESULTS: Elevated odds ratios (ORs) for each year increase in paternal
      age were found for cleft palate (OR. 1.02, 95% confidence interval [95% CI], 1.00
      1.04), diaphragmatic hernia (OR, 1.04; 95% CI, 1.02-1.06), right ventricular
      outflow tract obstruction (OR, 1.03; 95% CI, 1.01-1.04), and pulmonary valve
      stenosis (OR, 1.02, 95% CI, 1.01-1.04). At younger paternal ages, each year
      increase in paternal age correlated with increased odds of having offspring with
      encephalocele, cataract, esophageal atresia, anomalous pulmonary venous return,
      and coarctation of the aorta, but these increased odds were not observed at older
      paternal ages. The effect of paternal age was modified by maternal age for
      gastroschisis, omphalocele, spina bifida, all orofacial clefts, and septal heart
      defects. CONCLUSIONS: Our findings suggest that paternal age may be a risk factor
      for some multifactorial birth defects.

PMID- 20056437
TI  - Intraoperative pulmonary tumor embolism from renal cell carcinoma and a patent
      foramen ovale detected by transesophageal echocardiography.

PMID- 20056436
TI  - Remifentanil reduces the release of biochemical markers of myocardial damage
      after coronary artery bypass surgery: a randomized trial.
AB  - OBJECTIVE: Opioids, including remifentanil, have been demonstrated to confer
      cardiac protection against ischemia reperfusion injury in animals. This study
      evaluated whether remifentanil preconditioning is protective in first-time
      elective on-pump coronary artery bypass surgery patients receiving a standardized
      fentanyl (25 MUg/kg in total) and propofol anesthetic. DESIGN: A prospective,
      double blind, randomized, controlled study. SETTING: University hospital; single
      institution. PARTICIPANTS: Forty patients scheduled for first-time elective, on
      pump coronary artery bypass surgery for at least 3 diseased vessels.
      INTERVENTIONS: Patients randomized to the remifentanil group (n = 20) received a
      1 MUg/kg bolus followed by a 0.5 MUg/kg/min infusion for 30 minutes after
      induction but before sternotomy, while the control group (n = 20) received normal
      saline. Serial samples for measurement of creatine kinase (CK-MB), cardiac
      troponin I (cTnI), ischemia-modified albumin (IMA) and heart-type fatty-acid
      binding protein (hFABP) were taken at baseline, prebypass, T = 10 minutes, 2, 6,
      12, and 24 hours after cross-clamp release, to assess the degree of myocardial
      damage. MEASUREMENTS AND MAIN RESULTS: Patients in the remifentanil group had
      lower levels of CK-MB from T = 2 hours to 24 hours, cTnI from T = 10 minutes to T
      = 12 hours, IMA from T = 10 minutes to T = 2 hours and h-FABP from T = 10 minutes
      to T = 12 hours (p < 0.05). The time to tracheal extubation was shorter in
      patients in the remifentanil group. The overall lengths of ICU and hospital stays
      were not different. CONCLUSIONS: The addition of remifentanil to the anesthesia
      regimen reduced the degree of myocardial damage. This incremental benefit may be
      attributable either to remifentanil itself or to an overall increased opioid
      dose, the latter may be necessary to trigger cardiac protection.

PMID- 20056438
TI  - The effect of the suspension of the license for aprotinin on the care of patients
      undergoing cardiac surgery: a survey of cardiac anesthesiologists' and surgeons'
      opinions in the United Kingdom.
AB  - OBJECTIVE: The primary aim was to poll the opinions of cardiac anesthesiologists
      and surgeons as to the effect of the suspension of the license for aprotinin on
      patients undergoing cardiac surgery. DESIGN: A mailed questionnaire. SETTING:
      United Kingdom. PARTICIPANTS: Members of the Association of Cardiothoracic
      Anaesthetists and the Society for Cardiothoracic Surgery in Great Britain and
      Ireland with a UK address. INTERVENTIONS: A structured questionnaire.
      MEASUREMENTS AND MAIN RESULTS: Of the 546 dispatched surveys, 285 (52%) were
      returned. While the majority of respondents (61%) felt it had not had any effect,
      29% of respondents felt the suspension of the license for aprotinin had had a
      detrimental effect on patient care and 2% an extremely detrimental effect. Eight
      percent of respondents reported a beneficial effect. Since license suspension,
      the reported use of aprotinin had declined and tranexamic acid use had risen. The
      majority of respondents reported no change in the use of packed red cells (66%),
      blood products (53%), mechanical cell salvage (84%), factor VIIa (79%), or
      frequency of reopening for bleeding (65%). Respectively, 32%, 45%, 24%, and 20%
      of respondents reported a perceived increased use of these products, and 30%
      reported an increased frequency of reopening for bleeding. Apart from knowledge
      regarding local aprotinin stock, there was no significant difference in opinions
      between surgeons and anesthesiologists. CONCLUSIONS: While the majority of
      respondents felt that the suspension of the license for aprotinin had no effect,
      almost a third felt it had impacted negatively on the care of patients undergoing
      cardiac surgery.

PMID- 20056439
TI  - Inhaled nitroglycerin versus inhaled milrinone in children with congenital heart
      disease suffering from pulmonary artery hypertension.
AB  - OBJECTIVE: The aim of the present study was to compare the acute effects of
      inhaled milrinone and inhaled nitroglycerin on pulmonary and systemic
      hemodynamics in children with acyanotic congenital heart disease (left-to-right
      shunt) and pulmonary artery hypertension. DESIGN: Randomized clinical trial.
      SETTING: Catheterization laboratory of a tertiary care hospital. PARTICIPANTS:
      Thirty-five children below the age of 12 years who were suffering from acyanotic
      congenital heart disease with left-to-right intracardiac shunt and pulmonary
      artery hypertension (mean PA pressure > 30 mmHg). INTERVENTION: Right-heart
      catheterization was done using an end-hole balloon wedge pressure catheter.
      Baseline pulmonary and systemic hemodynamic parameters were recorded for all
      patients while breathing room air. All patients then underwent pulmonary
      vasodilator testing with 100% oxygen. Following this, patients were randomized
      into two groups and received either inhaled milrinone (group M, n = 18) or
      inhaled nitroglycerin (group N, n = 17) in a 50% air-oxygen mixture. Oximetry
      data were used to calculate systemic and pulmonary cardiac output based on Fick's
      principle. RESULTS: Systolic, diastolic, and mean pulmonary artery pressures
      decreased significantly in both the groups after drug nebulization, while there
      were no significant changes in systemic pressures. The percentage decrease from
      baseline in systolic (5.2% v 8.6%, p = 0.43), diastolic (19.5% v 16.8%, p = 0.19)
      and mean (14.9% v14.5%, p = 0.29) pulmonary artery pressures were comparable in
      both groups. The pulmonary vascular resistance index (PVRI) decreased from 9.0 +/
      3.9 to 2.9 +/- 1.7 Wood Units (WU)/m(2) in group M (p < 0.001) and from 8.6 +/-
      3.8 to 3.2 +/- 3.3 WU/m(2) in group N (p < 0.001). The fall in pulmonary artery
      pressures after drug nebulization in both groups was comparable to the fall seen
      with 100% oxygen. CONCLUSION: Both milrinone and nitroglycerin when given via the
      inhaled route significantly decrease systolic, diastolic and mean pulmonary
      artery pressures as well as PVRI without significant effects on systemic
      hemodynamics. Both the drugs given via inhaled route therefore can offer a good
      therapeutic choice and can help decrease the high inspired oxygen concentrations
      needed to treat pulmonary artery hypertensive episodes in perioperative settings.

PMID- 20056440
TI  - Speckle tracking for the intraoperative assessment of right ventricular function:
      a feasibility study.
AB  - OBJECTIVES: Speckle tracking is an ultrasound method that assesses B-mode
      features to measure tissue displacement and derive deformation parameters. The
      objective of this study was to assess the feasibility of using speckle tracking
      in the measurement of right ventricular (RV) longitudinal strain during cardiac
      surgery using transesophageal echocardiography (TEE). DESIGN: This was a
      prospective, observational cohort study. SETTING: A single university hospital
      setting. PARTICIPANTS: Twenty-one patients without valvular disease referred for
      coronary artery bypass graft surgery were studied. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: After the induction of anesthesia and mechanical
      ventilation, transthoracic echocardiography (TTE) and transesophageal
      echocardiography (TEE) were used to obtain tricuspid annular plane systolic
      excursion (TAPSE), RV fractional area of change (FAC), and 2-dimensional strain
      analysis (speckle tracking) on 3 consecutive heart beats. There was a larger
      percentage of measurable segments achieved when using TEE. All segments could be
      analyzed per cardiac cycle in 73% of loops when using TEE and 38% when using TTE.
      The global strain value was similar using both methods (TEE: -20.4%, TTE: 
      20.1%). The TAPSE could be measured in only 52% of the segments using TTE and
      100% using TEE. The FAC could be measured in 90.5% of the loops using TEE and in
      only 33.3% of the loops using TTE. CONCLUSIONS: Perioperative measurements of RV
      strain using TEE in ventilated patients is feasible. The success rate was higher
      using TEE in ventilated patients under anesthesia. Differences between the 2
      methods were likely the result of differences in 2-dimensional image quality.

PMID- 20056441
TI  - Argatroban "reversal" is caused by nonphysiologic stimulation of coagulation, not
      activated factor VII.

PMID- 20056442
TI  - Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac
      surgery.
AB  - OBJECTIVE: Hemorrhage continues to be a major problem after cardiac surgery
      despite the routine use of antifibrinolytic drugs, with striking inter-patient
      variability poorly explained by already known risk factors. The authors tested
      the hypothesis that genetic polymorphisms of inflammatory mediators and cellular
      adhesion molecules are associated with bleeding after cardiac surgery. DESIGN:
      Prospective, observational study. SETTING: Single, tertiary referral university
      heart center. PARTICIPANTS: Adult patients undergoing aortocoronary surgery with
      cardiopulmonary bypass. INTERVENTIONS: Patients (n = 759) had 10 mL of blood
      drawn preoperatively and genomic DNA isolated then genotyped for 17 polymorphisms
      in 7 candidate genes: tumor necrosis factor, interleukins 1beta and 6,
      interleukin 1 receptor antagonist, intercellular adhesion molecule-1 (ICAM-1), P
      selectin and endothelial leucocyte adhesion molecule-1 (E-selectin). Multivariate
      analyses were used to relate clinical and genetic factors to bleeding and
      transfusion. MEASUREMENTS AND MAIN RESULTS: The 98G/T polymorphism of the E
      selectin gene was independently associated with bleeding after cardiac surgery (p
      = 0.002), after adjusting for significant clinical predictors (patient size and
      baseline hemoglobin concentration). There was a gene dose effect according to the
      number of minor alleles in the genotype; carriers of the minor allele bled 17%
      (GT) and 54% (TT) more than wild type (GG) genotypes, respectively (p = 0.01).
      Carriers of the minor allele also had longer activated partial thromboplastin
      times (p = 0.0023) and increased fresh frozen plasma transfusion (p = 0.03)
      compared with wild type. CONCLUSIONS: The authors found a dose-related
      association between the 98T E-selectin polymorphism and bleeding after cardiac
      surgery, independent of and additive to standard clinical risk factors.

PMID- 20056443
TI  - High-frequency jet ventilation as an alternative method compared to conventional
      one-lung ventilation using double-lumen tubes during minimally invasive coronary
      artery bypass graft surgery.
AB  - OBJECTIVE: To optimize the conditions for the surgeon during minimally invasive
      direct coronary artery bypass (MIDCAB) and totally endoscopic coronary artery
      bypass (TECAB) procedures, one-lung ventilation (OLV) is required using double
      lumen tubes (DLT). This prospective study was designed to compare high-frequency
      jet ventilation (HFJV) of both lungs with the conventional method of OLV via DLT.
      DESIGN: Prospective, randomized, clinical study. SETTING: University-affiliated
      heart center. PARTICIPANTS: Forty patients with coronary artery disease and
      scheduled for elective MIDCAB or TECAB procedures were equally randomized into a
      DLT and an HFJV group. INTERVENTIONS: In the DLT group, OLV of the right lung was
      performed throughout the surgical procedure. In the HFJV group, patients received
      a conventional single-lumen endotracheal tube and both lungs were ventilated
      using HFJV. MEASUREMENTS: Hemodynamic, oxygenation and ventilation parameters
      were measured at the beginning of the operation, then 5, 15, 30, and 60 minutes
      after OLV/HFJV, as well as immediately before transfer to the ICU. MAIN RESULTS:
      Regarding the view of the surgical field, surgeons' comfort did not differ
      between methods. The intraoperative PaO(2) was significantly higher in the HFJV
      group compared with the DLT group at 5 (336.8 +/- 123.3 v 228.6 +/- 124.0; p =
      0.009) and 15 minutes (301.7 +/- 133.9 v 192.6 +/- 92.8; p = 0.012). The PaCO(2)
      was significantly higher in the HFJV group after 5 minutes and persisted through
      60 minutes of ventilation. The peak inspiratory pressure was significantly lower
      during HFJV (10.0 +/- 2.8 mbar v 32.1 +/- 5.9 mbar). CONCLUSIONS: HFJV in MIDCAB
      or TECAB procedures appears to be a feasible alternative to OLV using a DLT,
      although study in a larger population is required.

PMID- 20056444
TI  - Percutaneous left ventricular assist devices: clinical uses, future applications,
      and anesthetic considerations.

PMID- 20056445
TI  - Considerations about the association between preoperative statin administration
      and outcomes in patients undergoing CABG.

PMID- 20056447
TI  - Profound effects of cardiopulmonary bypass priming solutions on the fibrin part
      of clot formation: an ex vivo evaluation using rotation thromboelastometry.
AB  - OBJECTIVES: Dilutional coagulopathy as a consequence of cardiopulmonary bypass
      (CPB) system priming may also be affected by the composition of the priming
      solution. The direct effects of distinct priming solutions on fibrinogen, one of
      the foremost limiting factors during dilutional coagulopathy, have been minimally
      evaluated. Therefore, the authors investigated whether hemodilution with
      different priming solutions distinctly affects the fibrinogen-mediated step in
      whole blood clot formation. DESIGN: Prospective observational laboratory study.
      SETTING: University hospital laboratory. PARTICIPANTS: Eight male healthy
      volunteers. INTERVENTIONS: Blood samples diluted with gelatin-, albumin-, or
      hydroxyethyl starch (HES)-based priming solutions were ex-vivo evaluated for clot
      formation by rotational thromboelastometry. MEASUREMENTS AND MAIN RESULTS: The
      intrinsic pathway (INTEM) coagulation time increased from 186 +/- 19 seconds to
      205 +/- 16, 220 +/- 17, and 223 +/- 18 seconds after dilution with gelatin-,
      albumin-, or HES-containing prime solutions (all p < 0.05 v baseline). The
      extrinsic pathway (EXTEM) coagulation time was only minimally affected by
      hemodilution. Moreover, all 3 priming solutions significantly reduced the INTEM
      and EXTEM maximum clot firmness. The HES-containing priming solution induced the
      largest decrease in the maximum clot firmness attributed to fibrinogen, from 13
      +/- 1 mm (baseline) to 6 +/- 1 mm (p < 0.01 v baseline). CONCLUSIONS: All studied
      priming solutions prolonged coagulation time and decreased clot formation, but
      the fibrinogen-limiting effect was the most profound for the HES-containing
      priming solution. These results suggest that the composition of priming solutions
      may distinctly affect blood clot formation, in particular with respect to the
      fibrinogen component in hemostasis.

PMID- 20056448
TI  - Effects of single-dose gabapentin on postoperative pain and morphine consumption
      after cardiac surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the analgesic effect of
      single-dose preoperative gabapentin on postoperative pain and morphine
      consumption after cardiac surgery. DESIGN: A randomized, double-blind, placebo
      controlled, clinical study. SETTING: A single university hospital. PARTICIPANTS:
      Sixty patients undergoing coronary artery bypass graft surgery. INTERVENTIONS:
      Patients were randomly allocated into 2 groups preoperatively either to receive
      600 mg of oral gabapentin (GABA) or placebo (PLA) 2 hours before the operation.
      After extubation, an anesthesiologist blinded to the groups recorded pain scores
      both at rest and with cough with a 10-point verbal rating scale and sedation
      scores at 2, 6, 12, 18, 24, and 48 hours. Cumulative morphine consumption and the
      incidence of side effects were recorded during the study period. MEASUREMENTS AND
      MAIN RESULTS: The total morphine consumption was lower in the GABA group (6.7 +/-
      2.5 mg) than in the PLA group (15.5 +/- 4.6 mg, p < 0.01). Pain scores at rest
      were significantly lower in the GABA group than in the PLA group throughout the
      study period (p < 0.05 in all measurement times). Pain scores at 2, 6, and 12
      hours during coughing were significantly lower in the GABA group (p < 0.05). The
      number of oversedated patients was significantly higher in the GABA group at 2,
      6, and 12 hours of study compared with PLA (p < 0.001 at 2 and 6 hours and p <
      0.02 at 12 hours). The postoperative mechanical ventilation period was
      significantly prolonged in the GABA group (6.6 +/- 1.2 hours) compared with the
      PLA group (5.5 +/- 1 hours, p < 0.01). Nausea incidence was significantly lower
      in the GABA group (n = 9) than in the PLA group (n = 18, p = 0.02). CONCLUSIONS:
      Oral GABA at a dose of 600 mg given before cardiac surgery significantly reduced
      postoperative morphine consumption and postoperative pain both at rest and with
      cough.

PMID- 20056449
TI  - Synthetic synaesthesia and sensory substitution.
AB  - Visual information can be provided to blind users through sensory substitution
      devices that convert images into sound. Through extensive use to develop
      expertise, some blind users have reported visual experiences when using such a
      device. These blind expert users have also reported visual phenomenology to other
      sounds even when not using the device. The blind users acquired synthetic
      synaesthesia, with visual experience evoked by sounds only after gaining such
      expertise. Sensorimotor learning may facilitate and perhaps even be required to
      develop expertise in the use of multimodal information. Furthermore, other areas
      where expertise is acquired in dividing attention amongst cross-modal information
      or integrating such information might also give rise to synthetic synaesthesia.

PMID- 20056450
TI  - Insertional anatomy of the triceps brachii tendon.
AB  - HYPOTHESIS: Triceps tendon anatomy is important for surgical approaches to the
      elbow and tendon repair. The purpose of this study is to describe both the
      qualitative and quantitative anatomy of the triceps brachii tendon insertion.
      MATERIALS AND METHODS: Thirty-six elbows were dissected from twenty-three
      cadavers. Dimensions of the triceps tendon proper, lateral triceps expansion, and
      tendon insertion were measured. The central triceps tendon morphology was
      described. RESULTS: All specimens showed a distinct lateral tendon expansion
      continuous with the anconeus fascia (mean width, 16.8 mm). The mean width of the
      proper triceps tendon was 23.7 mm. The mean maximum olecranon width was 26.9 mm.
      The ratio of the triceps tendon width to the olecranon width averaged 0.88. The
      mean thickness of the central tendon insertion was 6.8 mm. The medial triceps
      tendon showed a distinct, rolled medial edge and an insertion consistently
      confluent with the central tendon. The triceps footprint insertion was dome
      shaped. The mean insertional width and length of the tendon proper were 20.9 mm
      and 13.4 mm, respectively. The mean distance from the olecranon tip to the tendon
      was 14.8 mm. The tendon width, thickness, and insertional dimensions correlated
      with the olecranon width. CONCLUSIONS: The lateral triceps expansion is a
      consistent anatomic finding with a width that is approximately 70% of the width
      of the central tendon. The triceps insertion has a broad width and narrow
      thickness that expands distally and correlates with the size of the olecranon.
      Knowledge of this anatomy will help the surgeon optimize surgical approaches and
      triceps repair techniques.

PMID- 20056451
TI  - Suprascapular neuropathy secondary to reverse shoulder arthroplasty: a case
      report.

PMID- 20056452
TI  - Reverse glenoid component fixation: is a posterior screw necessary?
AB  - BACKGROUND: Reverse shoulder arthroplasty has become more prevalent for the
      treatment of complex shoulder issues. Prosthetic designs vary in both the number
      and orientation of screws recommended for securing the glenoid base plate. This
      study examined the contribution of the posterior glenoid screw for stabilizing
      the glenosphere by comparing constructs with no posterior screw, a standard
      posterior screw directed into the glenoid neck, and a long posterior screw (LPS)
      into the scapular spine. MATERIAL AND METHODS: The Tornier RTSA glenoid implant
      was fixed into 2 groups of matched cadaveric scapulae. In both groups, the
      controls were fixed with a standard posterior screw (SPS). Matching scapulae had
      a screw configuration that omitted the posterior screw (NPS) in group I or
      utilized an LPS in group II. Specimens were tested using a "rocking-horse"
      protocol. During cyclic loading (50,000 cycles), the vertical displacement of the
      glenoid component was monitored using a digital caliper. RESULTS: In group I, NPS
      constructs demonstrated a significantly higher mean rate of loosening than SPS
      constructs. In group II, the LPS constructs demonstrated lower loosening rates
      than SPS constructs. Mean initial displacements were greater for NPS than SPS in
      group I and similar for SPS and LPS in group II DISCUSSION: The posterior glenoid
      screw contributes significantly to stability of the reverse glenoid base plate.
      If an SPS does not obtain good purchase into the scapula, glenoid component
      fixation will be enhanced by the addition of an LPS into the scapular spine.

PMID- 20056453
TI  - Reversed arthroscopic subacromial decompression for symptomatic irreparable
      rotator cuff tears: mid-term follow-up results in 34 shoulders.
AB  - BACKGROUND: In the elderly, there is no guideline for the treatment of
      irreparable rotator cuff lesions. The results of open or arthroscopic repair are
      variable. We hypothesized that the use of a reversed arthroscopic subacromial
      decompression (RASD) would yield comparable results. MATERIAL AND METHODS:
      Between January 2004 and December 2006, thirty-eight patients underwent a RASD
      for irreparable cuff tears in 39 shoulders. The surgical procedure consisted of a
      tenotomy of the long head of the biceps tendon, a debridement of the torn rotator
      cuff and a tuberoplasty, without violation of the coracoacromial arch and the
      acromion. RESULTS: Thirty-three patients (age 69.9 +/- 7.3 years) were available
      for clinical and radiological evaluation of 34 shoulders (male/female ratio:
      11/22), at a mean follow-up of 38 months (range: 21 months-52 months). Two of 33
      patients had required revision surgery, and were excluded from further
      statistical analysis. In the remaining 31 patients (32 shoulders), the modified
      Constant-Murley score (CMS) improved from 34.9% +/- 11.6 to 84.0% +/- 11.6 (p <
      0.0001). The preoperative mobility did not correlate with the final result.
      Preoperative pain was found to correlate negatively to the modified CMS at follow
      up (p= 0.0038). Although the acromiohumeral height decreased with 2.58 mm +/-
      1.68 and the severity of glenohumeral osteoarthritis increased with one grade
      (Samilson-Prieto classification), there was no correlation with the functional
      outcome. CONCLUSION: We conclude that for irreparable rotator cuff tears in the
      elderly, excellent mid-term results can be achieved with a RASD.

PMID- 20056454
TI  - Contribution of the supraspinatus to the external rotator lag sign: kinematic and
      electromyographic pattern in an in vivo model.
AB  - HYPOTHESIS: The external rotation lag sign (ERLS) is a test designed to assess
      the integrity of the supraspinatus (SSP) and infraspinatus tendons. This study
      intends to determine the electromyographic pattern of shoulder girdle muscles
      during a series of ERLS tasks conducted at full adduction and 20 degrees of
      elevation to figure out the better way to perform the test. The second aim is to
      assess the final contribution of the SSP to the ERLS by measuring the amount of
      lag after an SSP block induced by botulinum toxin. MATERIALS AND METHODS: Ten
      subjects with healthy shoulders were examined by a series of five ERLS trials at
      full adduction and 20 degrees of elevation in the scapular plane. Surface and
      intramuscular electromyographic activity of the shoulder girdle muscles was
      recorded and normalized against either the mean activity of all the muscles or
      the peak activity. The lag was simultaneously measured by an infrared
      optoelectronic system before and after the selective block of the SSP muscle.
      RESULTS: The SSP contributed 20% of the electrical activities during the ERLS,
      which was found to be significantly greater than the contributions of the other
      shoulder girdle muscles, except for the infraspinatus. The selective block of the
      SSP caused a lag of 4 degrees in all 10 shoulders at 20 degrees but no increase
      in lag at 0 degrees of elevation. CONCLUSIONS: The ERLS is potentially able to
      detect an isolated SSP tear if the test is performed correctly (20 degrees of
      abduction). The deltoid and biceps muscles are almost silent during the test,
      limiting confounding factors.

PMID- 20056455
TI  - Outcome of total elbow replacement for rheumatoid arthritis: single surgeon's
      series with Souter-Strathclyde and Coonrad-Morrey prosthesis.
AB  - BACKGROUND: The reported outcome of total elbow replacement is inferior to hip
      and knee arthroplasty, and there might be an element of institutional bias.
      METHODS: We analyzed the outcome of Souter and Coonrad-Morrey total elbow
      prosthesis in rheumatoid elbow performed by a single surgeon from a center
      independent from standpoint of being involved in the designing or manufacturing
      of the implant. RESULTS: We had 44 Souter elbows with a mean follow-up of 108
      months and 55 Coonrad-Morrey elbows with mean follow-up of 60 months. The Mayo
      Elbow Performance Score was comparable in both the groups with similar subjective
      satisfaction. Souter elbow showed a survivorship of 92.9% at 5 years and 76% at
      10 years, with aseptic loosening rate of 18% and instability of 9% as main
      reasons for the failure. The Coonrad-Morrey elbow shows 100% survival at mean
      follow-up of 5 years in our series. CONCLUSION: We find high rate of instability
      and loosening of Souter prosthesis with an inferior 5-year survival compared to
      Coonrad-Morrey prosthesis.

PMID- 20056456
TI  - Orthotopic bladder substitution following radical cystectomy in women:
      comparative study between sigmoid and ileal neobladders.
AB  - The objective of this study was to retrospectively compare the clinical outcomes
      of sigmoid and ileal neobladders (NBs) created in women. This study included 18
      and 14 women who underwent orthotopic NB reconstruction using sigmoid and ileal
      segment, respectively, after radical cystectomy, and postoperative clinical
      outcomes between the sigmoid and ileal NB groups (SNBG and INBG) were compared.
      Eighteen early and 7 late complications occurred in 12 and 6 women, respectively;
      however, there was no significant difference in the incidence of complications
      between SNBG and INBG. The proportion of patients who could void spontaneously in
      SNBG (94.4%) was significantly greater than that in INBG (64.3%), while there was
      no significant difference in continent status between these 2 groups. Despite the
      lack of significant differences in maximal flow rate and voided volume, post-void
      residual in SNBG (15.7 ml) was significantly smaller than that in INBG (62.0 ml).
      SF-36 survey for postoperative quality of life (QOL) did not show any significant
      differences in 7 of the 8 scores between the 32 women with NB and an age-matched
      control population; however, 3 of the 8 scores in SNBG were significantly
      superior to those in INBG. During the observation period of this study, urethral
      recurrence did not occur in any woman, and there was no significant difference in
      cancer-specific survival between the 2 groups. These findings suggest that it
      might be preferable to create sigmoid rather than ileal NB in women following
      radical cystectomy considering the favorable voiding function and QOL in SNBG.

PMID- 20056457
TI  - Biopsy accuracy in identifying unilateral prostate cancer depends on prostate
      weight.
AB  - OBJECTIVE: To evaluate the association between prostate weight and the diagnostic
      performance of routine biopsy schemes in detecting unilateral prostate cancer
      (PCa) that may be amenable to focal therapy. METHODS AND MATERIALS: Retrospective
      analysis of patients undergoing radical prostatectomy at Duke University Medical
      Center from 1990 to 2007. The cohort was dichotomized according to prostate
      weight (<=40 and >40 g) and further divided by biopsy scheme: 6-9 (sextant) and
      10-20 cores (extended). Diagnostic accuracy, sensitivity, specificity, and
      positive and negative predictive values were calculated within each prostate
      weight group and compared between biopsy schemes. RESULTS: A total of 859
      patients were included in the study. Patients with prostates >40 g were generally
      older and had higher PSA levels (P < 0.0001 and P = 0.036, respectively).
      Unilateral disease was more common in prostates >40 g both on biopsy (69% vs.
      60%, P = 0.009) and on final pathology (21% vs. 14%, P = 0.017) despite larger
      total tumor volume (6.1 vs. 4.8 cc, P < 0.001). Low grade PCa was also more
      common in larger glands (P = 0.003). Overall, extended biopsy schemes performed
      better than sextant but the benefit was statistically significant only in
      prostates >40 g. CONCLUSIONS: Despite having higher tumor volumes, men with
      prostate weight >40 g were more likely to have unilateral PCa than those with
      smaller prostates. In prostates >40 g, increasing the number of cores harvested
      at biopsy increased the diagnostic performance for detecting cancer laterality.
      Therefore, our results suggest that the benefit of more extensive tissue sampling
      may be higher in larger prostates compared with smaller ones when selecting
      candidates for prostate hemiablation.

PMID- 20056458
TI  - Does preoperative symptom classification impact prognosis in patients with
      clinically localized upper-tract urothelial carcinoma managed by radical
      nephroureterectomy?
AB  - OBJECTIVES: To evaluate if preoperative symptom classification could refine
      prediction of outcomes for patients with clinically localized upper-tract
      urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU). METHODS:
      Data on 654 patients with localized UTUC who underwent RNU were reviewed.
      Preoperative symptoms were classified as incidental (S1), local (S2), and
      systemic (S3). Clinical and pathologic data were compared between the cohorts.
      Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine
      recurrence-free and cancer-specific survival amongst the symptom cohorts.
      RESULTS: Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%),
      and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including
      higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence
      free and cancer-specific survival estimates were similar for patients with S1 and
      S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3
      symptoms (P < 0.001 for both). On multivariate analysis adjusting for final
      pathologic stage, grade, and LN status, S3 symptoms were not an independent
      predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P =
      0.07). Addition of symptom classification, however, increased the accuracy of a
      model consisting of stage, grade, and LNs for prediction of recurrence-free and
      cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both).
      CONCLUSIONS: Local symptoms do not confer worse prognosis compared with patients
      with incidentally detected UTUC. However, systemic symptoms are associated with
      worse outcomes despite apparently effective RNU. Patients with systemic symptoms
      may harbor micrometastatic disease and could potentially benefit from a more
      rigorous metastatic evaluation or perioperative chemotherapy regimens.

PMID- 20056459
TI  - CA125 for following up carcinoma of the bladder.

PMID- 20056460
TI  - Patterns of enlarged lymph nodes in patients with metastatic renal cell
      carcinoma.
AB  - OBJECTIVE: We reviewed the imaging studies of patients with known metastatic
      renal cell carcinoma (RCC) in order to more accurately assess where
      retroperitoneal lymphadenopathy occurs. METHODS: The database of patients with
      metastatic RCC was reviewed and 101 patients were found from 2002 to 2006. Each
      patient's CT scans were then reviewed. Twenty-seven retroperitoneal sections were
      defined for each patient, with 3 positions in each of the x-, y-, and z-axis.
      Lymph nodes greater than 1 cm were then counted for each section. RESULTS: Of the
      101 patients, 31, of whom 28 qualified, were found to have retroperitoneal
      lymphadenopathy of a least 1 cm or greater. Two-thirds of nodes (87 out of 124)
      exhibited a suprahilar, intra-aortocaval, and retro-aortocaval trend of lymph
      node enlargement. Three patients (11%) had isolated infrahilar nodes, while 8
      patients (29%) exhibited a skip lesion pattern by imaging criteria. Only 4
      patients (14%) were noted to have lymph nodes that were confined to the
      ipsilateral (paraaortic or paracaval) nodes in the perihilar and infrahilar
      region, which would be readily accessible during renal surgery. CONCLUSIONS:
      Lymphatic drainage in RCC is ill-defined, likely due to multiple lymphatic
      outflow channels. However, after a review of retroperitoneal lymphadenopathy
      imaging in patients with known metastatic RCC, there does seem to be a cephalad,
      posterior, and medial drainage pattern.

PMID- 20056461
TI  - Presence of oral lesions in leprosy patients does not imply involvement by
      Mycobacterium leprae.

PMID- 20056462
TI  - The role of environmental light in sleep and health: effects of ocular aging and
      cataract surgery.
AB  - Environmental illumination profoundly influences human health and well-being.
      Recently discovered photoreceptive retinal ganglion cells (pRGCs) are primary
      mediators of numerous circadian, neuroendocrine and neurobehavioral responses.
      pRGCs provide lighting information to diverse nonvisual (non-image-forming) brain
      centers including the suprachiasmatic nuclei (SCN) which serve as the body's
      master biological clock. The SCN exert functional control over circadian aspects
      of physiology. The timing and strength (amplitude) of SCN rhythmic signals are
      affected by light exposure. Light deficiency may attenuate SCN function and its
      control of physiological and hormonal rhythms which in turn can result in a
      cascade of adverse events. Inadequate pRGC photoreception cannot be perceived
      consciously, but may aggravate many common age-associated problems including
      insomnia, depression and impaired cognition. In this review we (1) summarize
      circadian physiology, emphasizing light's critical role as the most important
      geophysical timing cue in humans; (2) analyze evidence that typical residential
      lighting is insufficient for optimal pRGC requirements in youth and even more so
      with advancing age; (3) show how ocular aging and cataract surgery impact
      circadian photoreception; and (4) review some of the diverse morbidities
      associated with chronodisruption in general and those which may be caused by
      light deficiency in particular.

PMID- 20056463
TI  - Demographic characteristics of scrapie-affected holdings identified by active and
      passive surveillance schemes in Great Britain: 2002-2005.
AB  - Several surveillance techniques have been used to quantify the prevalence of both
      classical and atypical scrapie in British sheep, namely the recording of clinical
      suspects (RC) and the testing of animals slaughtered at abattoir (AS) or reported
      as fallen stock (FS). Any estimate of prevalence based on a particular source is
      likely to have been affected by demographic differences in the populations
      sampled. In this study, the demographic characteristics of scrapie-affected
      holdings detected by each of the surveillance streams (RC, AS, FS) in Great
      Britain were compared. Analyses of all three streams indicated that the
      probability of an affected holding being detected by a particular stream differed
      by geographical area, the number of animals brought onto the holding, the type of
      scrapie identified (classical vs. atypical) and the year. More detailed analysis
      of AS and FS suggested that the annual and regional differences between these
      surveys could be explained by differences in sampling effort.

PMID- 20056464
TI  - EPR characterization of ascorbyl and sulfur dioxide anion radicals trapped during
      the reaction of bovine Cytochrome c Oxidase with molecular oxygen.
AB  - The reaction intermediates of reduced bovine Cytochrome c Oxidase (CcO) were
      trapped following its reaction with oxygen at 50 micros-6 ms by innovative freeze
      quenching methods and studied by EPR. When the enzyme was reduced with either
      ascorbate or dithionite, distinct radicals were generated; X-band (9 GHz) and D
      band (130 GHz) CW-EPR measurements support the assignments of these radicals to
      ascorbyl and sulfur dioxide anion radical (SO2(-.)), respectively. The X-band
      spectra show a linewidth of 12 G for the ascorbyl radical and 11 G for the SO2(
      .) radical and an isotropic g-value of 2.005 for both species. The D-band spectra
      reveal clear distinctions in the g-tensors and powder patterns of the two
      species. The ascorbyl radical spectrum displays approximate axial symmetry with g
      values of g(x)=2.0068, g(y)=2.0066, and g(z)=2.0023. The SO2(-.) radical has
      rhombic symmetry with g-values of g(x)=2.0089, g(y)=2.0052, and g(z)=2.0017. When
      the contributions from the ascorbyl and SO2(-.) radicals were removed, no protein
      based radical on CcO could be identified in the EPR spectra.

PMID- 20056465
TI  - The solution structures of the cucumber mosaic virus and tomato aspermy virus
      coat proteins explored with molecular dynamics simulations.
AB  - The three-dimensional structures of two cucumovirus coat proteins (CP), namely
      Cucumber mosaic virus (CMV) and Tomato aspermy virus (TAV), were explored by
      molecular dynamics (MD) simulations. The N-terminal domain and the C-terminal
      tail of the CPs proved to be intrinsically unstructured protein regions in
      aqueous solution. The N-terminal alpha-helix had a partially unrolled
      conformation. The thermal factor analysis of the CP loop regions demonstrated
      that the CMV CP had more flexible loop regions than the TAV CP. The principal
      component analysis (PCA) of the MD trajectories showed that the first three
      eigenvectors represented the three main conformational motions in the CPs. The
      first motion components with the highest variance contribution described an
      opening movement between the hinge and the N-terminal domain of both CPs. The
      second eigenvector showed a closing motion, while the third eigenvector
      represented crosswise conformational fluctuations. These new findings, together
      with previous results, suggest that the hinge region of CPs plays a central role
      in the recognition and binding of viral RNA.

PMID- 20056466
TI  - Ensemble-based virtual screening reveals dual-inhibitors for the p53-MDM2/MDMX
      interactions.
AB  - The p53 protein, a guardian of the genome, is inactivated by mutations or
      deletions in approximately half of human tumors. While in the rest of human
      tumors, p53 is expressed in wild-type form, yet it is inhibited by over
      expression of its cellular regulators MDM2 and MDMX proteins. Although the p53
      binding sites within the MDMX and MDM2 proteins are closely related, known MDM2
      small-molecule inhibitors have been shown experimentally not to bind to its
      homolog, MDMX. As a result, the activity of these inhibitors including Nutlin3 is
      compromised in tumor cells over-expressing MDMX, preventing these compounds from
      fully activating the p53 protein. Here, we applied the relaxed complex scheme
      (RCS) to allow for the full receptor flexibility in screening for dual-inhibitors
      that can mutually antagonize the two p53-regulator proteins. First, we filtered
      the NCI diversity set, DrugBank compounds and a derivative library for MDM2
      inhibitors against 28 dominant MDM2-conformations. Then, we screened the MDM2 top
      hits against the binding site of p53 within the MDMX target. Results described
      herein identify a set of compounds that have been computationally predicted to
      ultimately activate the p53 pathway in tumor cells retaining the wild-type
      protein.

PMID- 20056467
TI  - Biochemical and molecular characterization of tyrosine hydroxylase deficiency in
      Hong Kong Chinese.
AB  - Tyrosine hydroxylase deficiency is a rare neurotransmitter disorder affecting the
      rate-limiting step in catecholamine biosynthesis. There are about 40 cases
      reported worldwide. Here, we report the biochemical and molecular findings of
      eight unrelated Chinese patients with tyrosine hydroxylase deficiency. We have
      identified eight novel mutations with 5 missense, 2 nonsense and 1 splicing
      mutations in the TH gene, namely p.R153X, p.R169X, p.G294R, p.G315S, p.A385V,
      p.I394T, p.G408R, and c.1163+5G>C. The mutations of the TH gene in Chinese are
      heterogeneous.

PMID- 20056468
TI  - Sonocatalytic degradation of organic dyes and comparison of catalytic activities
      of CeO2/TiO2, SnO2/TiO2 and ZrO2/TiO2 composites under ultrasonic irradiation.
AB  - The CeO(2)/TiO(2), SnO(2)/TiO(2) and ZrO(2)/TiO(2) composites were prepared by
      dispersing various nano-sized oxides (CeO(2), SnO(2), ZrO(2) and TiO(2)) with
      ultrasound and mixing TiO(2) with CeO(2), SnO(2) and ZrO(2), respectively, in
      boiling water in a molar ratio of 4:1, followed by calcining temperature 500
      degrees C for 60 min. Then a series of sonocatalytic degradation experiments were
      carried out under ultrasonic irradiation in the presence of CeO(2)/TiO(2),
      SnO(2)/TiO(2) and ZrO(2)/TiO(2) composites and nano-sized TiO(2) powder. Also,
      the influences of heat-treatment temperature and heat-treatment time on the
      sonocatalytic activities of CeO(2)/TiO(2), SnO(2)/TiO(2) and ZrO(2)/TiO(2)
      composites, and of irradiation time and solution acidity on the sonocatalytic
      degradation of Acid Red B were investigated by UV-vis spectra. It was found that
      the sonocatalytic degradation of Acid Red B shows significant variation in rate
      and ratio that decreases in order:
      CeO(2)/TiO(2)>SnO(2)/TiO(2)>TiO(2)>ZrO(2)/TiO(2)>SnO(2)>CeO(2)>ZrO(2), and the
      corresponding ratios of Acid Red B in aqueous solution are 91.32%, 67.41%,
      65.26%, 41.67%, 28.34%, 26.75% and 23.33%, respectively. And that the degradation
      ratio is only 16.67% under onefold ultrasonic irradiation. Because of the good
      degradation efficiency, this method may be an advisable choice for the treatment
      of non- or low-transparent wastewaters in the future.

PMID- 20056469
TI  - WITHDRAWN: The First International Summit of Noninvasive Ultrasound Treatment,
      Chongqing, China, October 22nd to 23rd 2009.
AB  - The Publisher regrets that this article is an accidental duplication of an
      article that has already been published, doi:10.1016/j.ultsonch.2009.12.011. The
      duplicate article has therefore been withdrawn.

PMID- 20056470
TI  - Ultrasound-induced membrane lipid peroxidation and cell damage of Escherichia
      coli in the presence of non-woven TiO2 fabrics.
AB  - A non-woven titanium dioxide (TiO(2)) fabric was applied to disinfection by
      ultrasound (US) irradiation, and the disinfection efficiency and lipid
      peroxidation of Escherichia coli (E. coli) cell membrane were evaluated to
      investigate the killing process. The addition of non-woven TiO(2) fabric enhanced
      hydroxyl (OH) radical generation and disinfection efficiency. Judging from the
      disinfection experiments using glutathione or t-butanol as a radical scavenger,
      the OH radical played a major role in cell killing in sonodynamic disinfection
      with non-woven TiO(2) fabric. Moreover, to understand the detailed killing
      process, damage to cell membrane was also evaluated using a diphenyl-1
      pyrenylphosphine (DPPP) fluorescent probe, which detects the membrane's lipid
      peroxidation. The addition of non-woven TiO(2) fabric aggravated this
      peroxidation. This aggravation was caused by the OH radical according to an assay
      using a radical scavenger. From these results, it was concluded that non-woven
      TiO(2) fabric as a sonocatalyst promoted peroxidation of the polyunsaturated
      phospholipid component of the lipid membrane initially and induced a major
      disorder in the E. coli cell membrane under US irradiation.

PMID- 20056471
TI  - Hiccups in Parkinson's disease: an overlooked non-motor symptom?
AB  - INTRODUCTION: Although hiccups may be a non-motor symptom of Parkinson's disease
      (PD), they have attracted little research attention to date. OBJECTIVE: To
      investigate the frequency of occurrence of hiccups in PD. METHOD: The presence of
      hiccups was evaluated using face-to-face interviews in 90 PD patients and 100 age
      matched controls. RESULTS: Eighteen (20%) of the PD patients and three (3%) of
      the control subjects reported frequent hiccups. The reported occurrence of
      hiccups was significantly higher in PD patients than controls. Nine patients
      noted that hiccups had appeared in the past, particularly around the onset of PD.
      One patient was admitted to our hospital because of intractable hiccups before a
      diagnosis of PD was made. Another eight patients reported the emergence of
      hiccups following the administration of antiparkinsonian drugs. CONCLUSION: Our
      results suggest that hiccups are more frequent in PD patients than healthy
      controls. Further studies are required to determine whether hiccups are
      associated with intrinsic pathology, to dopamine replacement therapy, or both.

PMID- 20056472
TI  - The active city? Disparities in provision of urban public recreation resources.
AB  - Recreation is critical to active living yet few studies have focused on
      disparities in the provision of recreational programs. We investigate the spatial
      distribution of public recreational programs in southern California. Findings
      indicate that more than half of all recreation programs take place away from a
      formal park site. Multivariate modeling results suggest that cities characterized
      by low household incomes, low fiscal capacity, minority populations, and multi
      family housing are disadvantaged with respect to recreation provisions. Such
      disparities may increase health risks among populations in such communities.
      Urban planners and public health advocates should enhance recreation programs in
      lower-income non-white communities.

PMID- 20056473
TI  - Combining atlas based segmentation and intensity classification with nearest
      neighbor transform and accuracy weighted vote.
AB  - In this paper, different methods to improve atlas based segmentation are
      presented. The first technique is a new mapping of the labels of an atlas
      consistent with a given intensity classification segmentation. This new mapping
      combines the two segmentations using the nearest neighbor transform and is
      especially effective for complex and folded regions like the cortex where the
      registration is difficult. Then, in a multi atlas context, an original weighting
      is introduced to combine the segmentation of several atlases using a voting
      procedure. This weighting is derived from statistical classification theory and
      is computed offline using the atlases as a training dataset. Concretely, the
      accuracy map of each atlas is computed and the vote is weighted by the accuracy
      of the atlases. Numerical experiments have been performed on publicly available
      in vivo datasets and show that, when used together, the two techniques provide an
      important improvement of the segmentation accuracy.

PMID- 20056474
TI  - Twenty first century trends in silicone hydrogel contact lens fitting: an
      international perspective.
AB  - Silicone hydrogel contact lenses were introduced into the market in 1999. To
      assess prescribing trends of this lens type since then, up to 1000 survey forms
      were sent to contact lens fitters in Australia, Canada, Japan, the Netherlands,
      Norway, the UK and the USA each year between 2000 and 2008. Practitioners were
      asked to record data relating to the first 10 contact lens fits or refits
      performed after receiving the survey form. Analysis of returned forms revealed a
      rapid increase in the prescribing of silicone hydrogel lenses over the survey
      period. In 2008, silicone hydrogel lenses represented 36% of all soft lenses
      prescribed. The categorization of the majority of lenses prescribed as 'refits'
      is primarily attributed to the mass conversion of lens wearers from hydrogel to
      silicone hydrogel lenses. Silicone hydrogels may soon represent the majority of
      soft contact lenses prescribed.

PMID- 20056475
TI  - Break in microkeratome oscillating pin during LASIK flap creation.
AB  - We describe the case of a 40-year-old female myope who presented for bilateral
      LASIK. Intra-operatively, the microkeratome oscillating pin broke during flap
      creation resulting in the separation of the disposable blade from the motor. This
      resulted in an irregular flap with missing pieces. The procedure was abandoned
      and the macerated partial flap repositioned as best as possible. The patient
      recovered a BCVA of 6/7.5. The manufacturer has since reported taking corrective
      measures to prevent this problem in the future. This case is a reminder that
      despite care and maintenance by user and manufacturer, extreme and rare hardware
      malfunctions can occur. Furthermore, although potentially sight threatening if
      managed well these complications can be followed by good recovery of vision.

PMID- 20056476
TI  - Overexpression of Id-1 is associated with tumor angiogenesis and poor clinical
      outcome in oral squamous cell carcinoma.
AB  - We analyzed the expression of Id-1 in oral squamous cell carcinoma (OSCC)
      immunohistochemically, and investigated the association of Id-1 expression with
      tumor angiogenesis and clinical prognosis. Overexpression of Id-1 protein was
      found in 83 out of 128 cases (64.8%). The expression of Id-1 was significantly
      associated with tumor size (p=0.013), lymph node metastasis (p=0.001), tumor
      stage (p=0.031) and tumor recurrence (p=0.003). Moreover, Id-1 expression was
      significantly correlated with intratumoral microvessel density (MVD) (r=0.223,
      p=0.011). The results suggest that overexpression of Id-1 was correlated with
      tumor angiogenesis and poor clinical outcome.

PMID- 20056477
TI  - Sugar signals and molecular networks controlling plant growth.
AB  - In recent years, several regulatory systems that link carbon nutrient status to
      plant growth and development have emerged. In this paper, we discuss the growth
      promoting functions of the hexokinase (HXK) glucose sensor, the trehalose 6
      phosphate (T6P) signal and the Target of Rapamycin (TOR) kinase pathway, and the
      growth inhibitory function of the SNF1-related Protein Kinase1 (SnRK1) and the
      C/S1 bZIP transcription factor network. It is crucial that these systems interact
      closely in regulating growth and in several cases crosstalk has been
      demonstrated. Importantly, these nutrient controlled systems must interact with
      other growth regulatory pathways.

PMID- 20056479
TI  - The spectroscopic (FT-IR, FT-IR gas phase, FT-Raman and UV) and NBO analysis of 4
      Hydroxypiperidine by density functional method.
AB  - In this work, we report a combined experimental and theoretical study on
      molecular structure, vibrational spectra, NBO and UV-spectral analysis of 4
      Hydroxypiperidine (4-HP). The FT-IR solid phase (4000-400 cm(-1)), FT-IR gas
      phase (5000-400 cm(-1)) and FT-Raman spectra (3500-50 cm(-1)) of 4-HP was
      recorded. The molecular geometry, harmonic vibrational frequencies and bonding
      features of 4-HP in the ground-state have been calculated by using the density
      functional methods (BLYP, B3LYP) with 6-311G (d,p) as basis set. The assignments
      of the vibrational spectra have been carried out with the help of normal co
      ordinate analysis (NCA) following the Scaled Quantum Mechanical Force Field
      Methodology (SQMFF). Stability of the molecule arising from hyperconjugative
      interactions, charge delocalization has been analyzed using natural bond orbital
      (NBO) analysis. The results show that charge in electron density (ED) in the
      sigma* antibonding orbitals and E (2) energies confirms the occurrence of ICT
      (Intra-molecular Charge Transfer) within the molecule. The UV spectrum was
      measured in ethanol solution. The energy and oscillator strength calculated by
      Time-Dependent Density Functional Theory (TD-DFT) result complements the
      experimental findings. The calculated HOMO and LUMO energies show that charge
      transfer occurs within the molecule. Finally the calculation results were applied
      to simulated infrared and Raman spectra of the title compound which show good
      agreement with observed spectra.

PMID- 20056478
TI  - Contrasting persistence strategies in Salmonella and Mycobacterium.
AB  - Long-term survival of persistent bacterial pathogens in mammalian hosts
      critically depends on their ability to avoid elimination by innate and adaptive
      immune responses. The persistent human pathogens that cause typhoid fever and
      tuberculosis exemplify alternative strategies for survival in the host: immune
      evasion and immune adaptation, respectively. Salmonella enterica serotype Typhi
      evades host innate immune responses and inflammation by expressing factors that
      interfere with its detection as a Gram-negative bacterium, enabling persistent
      colonization of an immunologically privileged niche, the gallbladder. In
      contrast, Mycobacterium tuberculosis has adapted to survive within phagocytic
      cells, which typically eliminate invading microbes, by deploying stress
      resistance mechanisms that counteract the harsh environment of the phagolysosome.

PMID- 20056480
TI  - Viro-immunological dynamics in HIV-1-infected subjects receiving once-a-week
      emtricitabine to delay treatment change after failure: a pilot randomised trial.
AB  - BACKGROUND: In HIV-1-infected patients harbouring the M184V mutation (M184V),
      lamivudine monotherapy leads to a smaller decrease in CD4 percentages (CD4%) than
      treatment interruption, possibly due to the reduced fitness of the mutated virus.
      OBJECTIVE: We assessed whether a minimal dose of a cytidine analogue that is
      theoretically sufficient to maintain M184V (one emtricitabine tablet once-weekly)
      may be as effective. STUDY DESIGN: In a proof-of-concept, randomised clinical
      trial, HIV-1-infected patients with CD4 cells >400/mm(3), failing on lamivudine-
      or emtricitabine-containing combination antiretroviral therapy (cART), received
      emtricitabine once-a-week (A), or emtricitabine once-a-day (B), or lamivudine
      once-a-day (C). The primary endpoint was the proportion of subjects without a 12
      week loss in CD4%. The patients resumed cART after 24 weeks or in the case of CD4
      cells <350/mm(3). RESULTS: The 38 enrolled patients had similar baseline
      characteristics across groups. The primary endpoint was reached by 5/13 patients
      (38.5%) in arm A, 3/13 (23.1%) in arm B, and 3/12 (25%) in arm C (P=0.644), and
      respectively 4/13 (30.8%), 4/13 (30.8%) and 5/12 (41.7%) had to resume cART
      within 24 weeks (P=0.805). The immunological changes over 24 weeks were similar
      in the three groups, but there was a higher median viral rebound in once-weekly
      treatment recipients (A) than in once-daily (B+C): 0.97 versus
      0.52log(10)copies/ml (P=0.033). M184V was maintained in all the participants.
      CONCLUSIONS: Once-weekly emtricitabine led to a higher viral rebound than once
      daily monotherapy, but similar immunological changes, thus suggesting a role of
      M184V in slowing the decrease in CD4% in treatment failing subjects.

PMID- 20056481
TI  - Waterborne gastroenteritis outbreak at a scouting camp caused by two norovirus
      genogroups: GI and GII.
AB  - BACKGROUND: A cross-border gastroenteritis outbreak at a scouting camp was
      associated with drinking water from a farmer's well. OBJECTIVES: A retrospective
      cohort study was performed to identify size and source of the outbreak, as well
      as other characteristics. STUDY DESIGN: Epidemiological investigation included
      standardized questionnaires about sex, age, risk exposures, illness and family
      members. Stool and water (100mL) samples were analyzed for bacteria, viruses and
      parasites. RESULTS: Questionnaires were returned by 84 scouts (response rate
      82%), mean age of 13 years. The primary attack rate was 85% (diarrhoea and/or
      vomiting). Drinking water was the strongest independent risk factor showing a
      dose-response effect with 50%, 75%, 75%, 93% and 96% case prevalence for 0, 1, 2
      3, 4-5 and >5 glasses consumed, respectively. Norovirus (GI.2 Southampton and
      GII.7 Leeds) was detected in 51 stool specimens (75%) from ill scouts. Water
      analysis showed fecal contamination, but no norovirus. The secondary attack rate
      was 20%. CONCLUSIONS: This remarkable outbreak was caused by a point-source
      infection with two genogroups of noroviruses most likely transmitted by drinking
      water from a well. Finding a dose-response relationship was striking. Specific
      measures to reduce the risk of waterborne diseases, outbreak investigation and a
      good international public health network are important.

PMID- 20056482
TI  - Respiratory viruses, a common microbiological finding in neutropenic children
      with fever.
AB  - BACKGROUND: Febrile neutropenia is a common complication in children undergoing
      chemotherapy for malignancies. A microbial agent is only identified in 15-30% of
      the fever episodes and corresponds mostly to bacterial findings. OBJECTIVE: To
      investigate viral infections as possible etiologic agents in episodes of febrile
      neutropenia. STUDY DESIGN: Nasopharyngeal aspirates (NPAs) from patients
      presenting with neutropenic fever at two pediatric oncology wards in Sweden and
      Australia were analyzed with a conventional virus-diagnostic approach and RT-PCR.
      Coupled blood samples were analyzed for the detection of CMV, EBV, adenovirus and
      erythrovirus. Bacterial blood culture was performed routinely. RESULTS:
      Conventional virus-diagnostic approach coupled to routinely performed bacterial
      analyzes revealed an infectious agent in 29% compared to 60% when using PCR. By
      adding PCR, a viral pathogen was detected in 46% of the NPAs and in 4% of the
      blood samples collected. In half of the patients with bacteremia, respiratory
      tract viruses were co-detected. CONCLUSION: Respiratory viruses were frequently
      detected in NPAs suggesting a significant role of viral infections in children
      presenting with neutropenic fever. The meaning of these findings needs to be
      further evaluated but has the potential to individualize infection treatment and
      to reduce the extensive use of antibiotics in immunocompromised children with
      neutropenia.

PMID- 20056483
TI  - Higher blood concentrations of synthetic musks in women above fifty years than in
      younger women.
AB  - Synthetic musk compounds are widely used as fragrance ingredients in many
      consumer products. Little is known about their accumulation in humans and
      especially in older persons. In this study, we determined concentrations of 11
      synthetic musks in women above fifty years and compared the results with earlier
      results from samples of young females. Blood was taken from 53 women above 50
      years of age, visiting outpatients of the Department of Angiology at the Hanusch
      Krankenhaus in Vienna, Austria. The used analytical methods consist of an
      extraction and clean-up step and a chromatographic analysis by GC/MS. Tonalide-D3
      was used as recovery standard in all samples. Hexachlorobenzene (13)C(6) was used
      as internal standard. Study participants also completed a questionnaire on the
      use of cosmetics, about nutrition and other life-style aspects. The two
      substances which could be detected in higher percentages of the blood plasma
      samples were galaxolide (89 percent, maximum concentration 6900 ng/L) and musk
      xylene (62 percent, maximum concentration 190 ng/L). Regression analysis revealed
      a significant association of galaxolide concentration with frequent use of
      perfumes, deodorants and shampoos. Frequent use of soaps and fabric softener was
      associated with higher plasma concentrations of musk xylene. Nutrition habits,
      skin type, body mass index or surface area were not related to plasma
      concentration of these musk compounds. From the study group investigated older
      persons showed higher plasma concentrations. These findings could be due to the
      higher use of lotions and cremes on face and hands and a more frequent use of
      skin care products because older persons reported more frequently dry skin. In
      addition, physiological aging related changes might be responsible for higher
      dermal absorption of synthetic musks. These results indicate that more focus on
      aging tissues is needed.

PMID- 20056484
TI  - Regulatory T cells in malaria--friend or foe?
AB  - T cell-mediated inflammatory immune responses contribute to both the clearance
      and pathology of malaria infections; the host's ability to down-regulate
      inflammation once parasitemia is controlled is crucial to avoid immune-mediated
      pathology but remains poorly understood. Various regulatory populations of T
      lymphocytes can modulate inflammatory immune responses and there has been
      considerable recent interest in the potential for regulatory T cells to modify
      the outcome of both murine and human malaria infections. Here, we review these
      studies, focussing in particular on recent studies in humans, propose a model by
      which different regulatory T cell populations might contribute to the control of
      inflammation at different stages of infection and discuss the implications for
      the design of safe and effective malaria vaccines.

PMID- 20056485
TI  - Evolutionary forces on Anopheles: what makes a malaria vector?
AB  - In human malaria, transmission intensity is highly dependent on the vectorial
      capacity and competence of local mosquitoes. Most mosquitoes are dead ends for
      the parasite, and only limited ranges of Anopheles are able to transmit
      Plasmodium to humans. Research to understand the determinants of vectorial
      capacity and competence has greatly progressed in recent years; however, some
      aspects have been overlooked and the evolutionary pressures that affect them
      often neglected. Here, we review key factors of vectorial capacity and competence
      in Anopheles, with a particular focus on the most important malaria vector
      Anopheles gambiae. We aim to point out selection pressures exerted by Plasmodium
      on Anopheles to improve its own transmission and discuss how the parasite might
      shape the vector to its benefit.

PMID- 20056486
TI  - Giardiasis--why do the symptoms sometimes never stop?
AB  - Although giardiasis is considered by most medical practitioners to be an easily
      treated infection, prolonged symptoms due to, or following, Giardia duodenalis
      infection can have a significant impact on quality of life. Symptom recurrence,
      including abdominal symptoms and fatigue, can result from re-infection, treatment
      failure, disturbances in the gut mucosa or post-infection syndromes. In developed
      countries, these sequelae can have an enormous impact on quality of life; in
      developing countries, particularly in children, they add yet another burden to
      populations that are already disadvantaged. Here, we outline current knowledge,
      based on individual case sequelae from sporadic infections, observations of
      population effects following outbreaks and studies of phenotypic and genotypic
      diversity between morphologically identical isolates of parasites. We also raise
      further questions, looking for clues as to why giardiasis sometimes becomes an
      intrusive, long-term problem.

PMID- 20056487
TI  - Anticancer agents against malaria: time to revisit?
AB  - The emergence of artemisinin resistance could adversely impact the current
      strategy for malaria treatment; thus, new drugs are urgently needed. A possible
      approach to developing new antimalarials is to find new uses for old drugs. Some
      anticancer agents such as methotrexate and trimetrexate are active against
      malaria. However, they are commonly perceived to be toxic and thus not suitable
      for malaria treatment. In this opinion article, we examine how the toxicity of
      anticancer agents is just a matter of dose or 'only dose makes the poison', as
      coined in Paracelsus' law. Thus, the opportunity exists to discover new
      antimalarials using the anticancer pharmacopoeia.

PMID- 20056488
TI  - Evaluation of 24 locus MIRU-VNTR genotyping of Mycobacterium tuberculosis
      isolates in Canada.
AB  - The current gold standard for Mycobacterium tuberculosis complex (MTBC)
      genotyping is insertion sequence (IS) 6110 restriction fragment length
      polymorphism (RFLP) as it provides the highest discriminatory power of all
      available MTBC genotyping methods. However, RFLP is labour intensive and the
      interpretation of data from this method can be susceptible to errors. In 2001 a
      rapid, reproducible variable number of tandem repeat (VNTR) based typing method
      using 12 mycobacterial interspersed repetitive units (MIRU) was developed.
      Despite this advancement, this method lacked the discriminatory power of IS6110
      RFLP. More recently a set of 24 MIRU-VNTR loci was reported to have greater
      discriminatory power than the original 12 locus system and may exceed that of
      RFLP when combined with spoligotyping. We compared the 24 locus method to the 12
      locus method in order to improve surveillance of tuberculosis in Canada. A random
      sample of 650 MTBC isolates from British Columbia, Saskatchewan, Manitoba and
      Quebec Canada was genotyped using the 24 MIRU loci. Comparison of the data for
      the 12 and 24 MIRU loci showed an increase of the Hunter-Gaston discriminatory
      index (HGDI) from 0.895 (12 loci) to 0.920 (24 loci). The implementation of the
      24 locus MIRU-VNTR methods offers improvement in discriminatory power over the
      traditional 12 locus method. For long-term surveillance of MTBC within Canada,
      the use of 24 MIRU-VNTR loci will provide rapid, highly discriminatory molecular
      epidemiology information.

PMID- 20056489
TI  - Incidence, case fatality, and functional outcome of intracerebral haemorrhage
      over time, according to age, sex, and ethnic origin: a systematic review and meta
      analysis.
AB  - BACKGROUND: Since the early 1980s, imaging techniques have enabled population
      based studies of intracerebral haemorrhage. We aimed to assess the incidence,
      case fatality, and functional outcome of intracerebral haemorrhage in relation to
      age, sex, ethnic origin, and time period in studies published since 1980.
      METHODS: From PubMed and Embase searches with predefined inclusion criteria, we
      identified population-based studies published between January, 1980, and
      November, 2008. We calculated incidence and case fatality. Incidences for
      multiple studies were pooled in a random-effects binomial meta-analysis. Time
      trends of case fatality were assessed with weighted linear-regression analysis.
      FINDINGS: 36 eligible studies described 44 time periods (mid-year range 1983
      2006). These studies included 8145 patients with intracerebral haemorrhage.
      Incidence did not decrease between 1980 and 2008. Overall incidence was 24.6 per
      100 000 person-years (95% CI 19.7-30.7). Incidence was not significantly lower in
      women than in men (overall incidence ratio 0.85, 95% CI 0.61-1.18). Using the age
      group 45-54 years as reference, incidence ratios increased from 0.10 (95% CI 0.06
      0.14) for people aged less than 45 years to 9.6 (6.6-13.9) for people older than
      85 years. Median case fatality at 1 month was 40.4% (range 13.1-61.0) and did not
      decrease over time, and was lower in Japan (16.7%, 95% CI 15.0-18.5) than
      elsewhere (42.3%, 40.9-43.6). Six studies reported functional outcome, with
      independency rates of between 12% and 39%. Incidence of intracerebral haemorrhage
      per 100 000 person-years was 24.2 (95% CI 20.9-28.0) in white people, 22.9 (14.8
      35.6) in black people, 19.6 (15.7-24.5) in Hispanic people, and 51.8 (38.8-69.3)
      in Asian people. INTERPRETATION: Incidence of intracerebral haemorrhage increases
      with age and has not decreased between 1980 and 2006. Case fatality is lower in
      Japan than elsewhere, increases with age, and has not decreased over time. More
      data on functional outcome are needed. FUNDING: Netherlands Heart Foundation.

PMID- 20056490
TI  - Intracerebral haemorrhage: a need for more data and new research directions.

PMID- 20056491
TI  - Sleep disordered breathing, insomnia, and health related quality of life -- a
      comparison between age and gender matched elderly with heart failure or without
      cardiovascular disease.
AB  - AIMS: The aims of this study are (I) to compare the prevalence of sleep
      disordered breathing (SDB) and insomnia between elderly with heart failure (HF)
      and age and gender matched elderly without cardiovascular disease (CVD), and (II)
      to examine the association between HF, SDB and insomnia, as well as their impact
      on health related quality of life (Hr-QoL). METHODS: Three hundred and thirty-one
      elderly (71-87 years) community-living individuals underwent sleep recordings and
      echocardiography. Questionnaires assessed insomnia and Hr-QoL. Comparisons were
      made between age and gender matched individuals with HF (n=36) and without CVD
      (n=36). RESULTS: The HF group had higher mean apnoea-hypopnoea index (17.6 vs.
      6.3, p<0.001). Moderate/severe SDB was found in 42% of those with HF vs. 8% in
      those without CVD (p=0.001). Those with HF had more difficulties maintaining
      sleep (DMS) (72% vs. 50%, p=0.05) and excessive daytime sleepiness (EDS) (25% vs.
      8%, p=0.05) and scored worse Hr-QoL in five of eight SF-36 domains. In regression
      analysis SDB had no association to Hr-QoL. DMS associated to the physical-, and
      non restorative sleep to the mental domain of Hr-QoL. SDB had no correlations to
      insomnia or EDS. CONCLUSIONS: SDB, DMS and EDS are more common in elderly with
      HF. SDB is not an obvious cause for sleep complaints or poor Hr-QoL in elderly.

PMID- 20056492
TI  - Tourette syndrome and epilepsy: a strange case of possible sudden unexpected
      death.
AB  - Mechanisms of sudden unexpected death in epilepsy (SUDEP) are incompletely
      understood in part because the overwhelming majority of patients are not
      undergoing video telemetry when they die. Described here is a patient with
      Tourette syndrome and epilepsy who displayed a dangerous compulsive tic resulting
      in carotid occlusions and seizures as captured on video telemetry monitoring. He
      was later found dead, raising the possibility of SUDEP. Possible mechanisms of
      SUDEP are discussed in light of video, EEG, ECG, epilepsy and tic behaviors.

PMID- 20056493
TI  - Visual memory in patients after anterior right temporal lobectomy and adult
      normative data for the Brown Location Test.
AB  - Several large meta-analytic studies have failed to support a consistent
      relationship between visual or "nonverbal" memory deficits and right mesial
      temporal lobe changes. The Brown Location Test (BLT), a recently developed dot
      location learning and memory test, uses a nonsymmetrical array and provides
      control over many of the confounding variables (e.g., verbal influence and
      drawing requirements) inherent in other measures of visual memory. In the present
      investigation, we evaluated the clinical utility of the BLT in patients who had
      undergone left or right anterior mesial temporal lobectomy. We also provide
      normative data of 298 healthy adults for standardized scores. Results revealed
      significantly worse performance on the BLT in the right as compared to the left
      lobectomy group and the healthy adult normative sample. The present findings
      support a role for the right anterior mesial temporal lobe in dot location
      learning and memory.

PMID- 20056494
TI  - The cognitive impact of epileptiform EEG discharges and short epileptic seizures:
      relationship to characteristics of the cognitive tasks.
AB  - OBJECTIVE: We analyzed the effect of task dimensions (information processing
      demand; duration of the test; input modality) on the occurrence and cognitive
      impact of epileptiform EEG discharges (EEDs) or subtle epileptic seizures.
      METHODS: One hundred ninety-nine children, aged 6-17 years, were included
      consecutively in a prospective standardized study. All children were assessed
      with EEG, which was synchronized with a computerized cognitive FePsy test system.
      RESULTS: No association was found between the occurrence of EEDs or subtle
      epileptic seizures and the three task dimensions introduced in our study. The
      Computerized Visual Searching Task (CVST) appeared to be particularly sensitive
      to direct cognitive effects of EEDs. The CVST and the three memory tests--Corsi's
      Block Tapping and recognition of words/figures--were sensitive to the cognitive
      effects of subtle epileptic seizures. CONCLUSION: Our results do not indicate a
      distinctive effect of information processing demand, duration of the test, or
      input modality on the occurrence of EEDs or subtle epileptic seizures. Effects on
      the impact on cognition are found when these three factors are combined.

PMID- 20056495
TI  - Disparities in injury death location for people with epilepsy/seizures.
AB  - OBJECTIVE: Wide variation has been reported in the proportion of injury deaths
      occurring during the prehospital phase. Potential disparities in where injured
      people with epilepsy and seizure disorders die have not been examined. We
      compared location of death between injured patients with epilepsy and seizure
      disorders and similar patients without epilepsy/seizures and tested the
      hypothesis that injured people with epilepsy/seizures are more likely to die
      outside of a hospital or health care setting. METHODS: U.S. vital statistics
      (mortality) data from the multiple cause of death files of the National Center
      for Health Statistics were analyzed. Patients less than 65 years of age at death
      who had injury as the underlying cause of death were included. Multinomial
      logistic regression was used to assess location of death, controlling for patient
      and injury characteristics. RESULTS: Controlling for potential confounders,
      people with epilepsy/seizures were more likely to die at home from unintentional
      injuries (relative risk ratio [RRR]=1.51, P<0.001) and less likely to die in
      public places (RRR=0.27, P<0.001). People with epilepsy/seizures were less likely
      to die at home or in public places from suicide, but significantly more likely to
      die at home from homicide (RRR=2.29, P<0.001). By mechanism of injury, people
      with epilepsy/seizures were more likely to die at home from drowning (RRR=2.35,
      P<0.001). DISCUSSION: Disparities in where injured people with epilepsy/seizures
      die deserve further attention. Identifying the underlying causes of these
      disparities will allow for the development of targeted prevention interventions.

PMID- 20056496
TI  - Interictal mood disorder and quality of life in active epilepsy.
AB  - Although it is known that depressive symptoms have significant impact on quality
      of life (QOL) in epilepsy and that atypical symptoms are common in interictal
      depression, less is known about the clinical significance of the atypical form of
      interictal depression as opposed to major depressive disorder (MDD). We compared
      quality of life among 30 patients with epilepsy (1) with major depressive
      disorder (group D), (2) with interictal dysphoric disorder (group ID), and (3)
      without MDD or IDD (group ND). The mean t scores on the 31-item Quality of Life
      in Epilepsy questionnaire were lower in groups D (20.3, 95% CI 9.02-31.7, n=3)
      and ID (38.7, 95% CI 34.2-43.2, n=19) compared with group ND (59.1, 95% CI 52.2
      66.1, n=8). These results underscore the clinical significance of IDD that not
      only accounts for a large portion of mood symptoms in the population with
      epilepsy, but also is not adequately captured by the DSM-IV criteria for MDD.

PMID- 20056497
TI  - Unusual migration of an abandoned fractured lead.

PMID- 20056498
TI  - Supraventricular tachycardia with atrioventricular block: what is the mechanism?

PMID- 20056499
TI  - Ventricular safety pacing, ventricular sense response, and ventricular
      tachycardia.
AB  - The ventricular sense response (VSR) algorithm enforces biventricular pacing on
      ventricular sensing to maximize biventricular pacing in patients with atrial
      fibrillation. This report describes a case of recurrent ventricular tachycardia
      that may be facilitated by this enforced pacing algorithm.

PMID- 20056500
TI  - The role of in vivo beta-adrenergic stimulation on sweat production during
      exercise.
AB  - The purpose of the current study was to investigate the role of in vivo beta
      adrenergic stimulation on sweat production during exercise. To do this, atropine
      was used to block the cholinergic component of sweating, thus isolating any
      potential beta-adrenergic response during exercise. The subjects for this study
      were 11 healthy volunteers. Atropine (1% solution) and aminophylline (1%
      solution) were administered to a 5 cm(2) area of the flexor surface of one
      forearm via iontophoresis. The opposing arm underwent iontophoresis with a saline
      solution. Each subject then exercised at 75% of their age-predicted maximum heart
      rate. During exercise, mean+/-SD sweat rate in the control forearm was 0.63+/
      0.50mg/cm(2)/min. There was no measurable sweat production in the arm pre-treated
      with atropine and aminophylline. Following exercise, iontophoresis of pilocarpine
      verified complete cholinergic blockade in the treated forearm. The results of the
      current study suggest that in vivo beta-adrenergic stimulation alone is not
      sufficient to elicit sweating in exercising humans. Such data supports previous
      studies that have suggested that the role of beta-adrenergic stimulation in vivo
      is to potentiate cholinergic sweating.

PMID- 20056501
TI  - Trends in acute non-variceal bleeding in Israel in 1996-2007: a significant
      decrease in the rates of bleeding peptic ulcers.
AB  - BACKGROUND: A decrease in the incidence of hospital admissions for acute non
      variceal upper GI bleeding (AUGIB) has been reported in regions with a low
      prevalence of Helicobacter pylori (HP) infection. AIM: To investigate trends in
      hospital admissions for AUGIB in Israel, where the prevalence of HP infection is
      intermediate. METHODS: We have searched the National Hospital Discharge Database
      of the Israeli Ministry of Health, where all admissions to acute care hospitals
      for the period January 1, 1996 through December 31, 2007 are compiled. Using a
      validated strategy, we identified all admissions for AUGIB according to ICD-9-CM
      codes. Incidence rates were calculated and adjusted to reflect the age and gender
      distribution of the Israeli population. RESULTS: The overall rates of hospital
      admissions for AUGIB decreased significantly from 29.3 to 16.8
      cases/10(5)population/year (p<0.0001). The decreases were similar in both
      genders. This decrease was due to decreased rates of bleeding from duodenal
      ulcers (from 13.6 to 5 cases/10(5)population/year) and gastric ulcers (from 4.3
      to 2.4 cases/10(5)population/year). The rates of bleeding from other causes
      remained unchanged. The rates of surgical interventions bleeding control
      decreased significantly (overall from 11 to 4%). The in-hospital mortality rate
      varied between 7.6 and 7%, did not change significantly in both genders but
      increased significantly with age during the study period. CONCLUSIONS: A decline
      in the overall incidence of AUGIB during the study period was due to a
      significant decrease in the rate of bleeding peptic ulcers.

PMID- 20056502
TI  - A case of deep burns, while diving The Lusitania.
AB  - We present the first documented case of severe burns, sustained by a diver as a
      result of auto-ignition of air-activated heat packs at high partial pressure of
      oxygen and high ambient pressure. Our patient was diving the shipwreck of The
      Lusitania off the south coast of Ireland. This is a significant wreck, lying 90
      metres down on the seabed. Torpedoed by a German U-boat in 1915, its loss
      prompted American involvement in WW1. Several unlikely events combined in this
      case to bring about serious and life threatening injuries. Herein we discuss the
      case and explore some of the physical and chemical processes that lead to these
      injuries.

PMID- 20056503
TI  - Use of cyanoacrylate compounds in vascular anastomosis.

PMID- 20056504
TI  - Classification of soft-tissue degloving in limb trauma.
AB  - Compressive, tortional and abrasive deforming forces are translated to the limbs
      during high energy trauma. The long bones may be fractured in many patterns with
      a varying extent of fragmentation and comminution but the soft-tissues appear to
      absorb the forces in a predictable way. We retrospectively reviewed a series of
      79 complex limb injuries treated in a dedicated centre where the clinical notes
      and photo-documentation were meticulously kept and where the outcomes were known.
      The soft-tissue injuries were then described and revealed four patterns of
      injury: abrasion/avulsion, non-circumferential degloving, circumferential single
      plane and circumferential multi-plane degloving. These patterns occurred either
      in isolation or occasionally in combination. Resuturing of degloved skin was only
      successful in non-circumferential (pattern 2) cases. Radical excision of
      devitalised tissue followed by soft-tissue reconstruction in a single procedure
      was successful in all patterns apart from pattern 4 (circumferential multi-plane
      degloving). In pattern 4 we recommend serial wound excision prior to
      reconstruction.

PMID- 20056505
TI  - Capsular flap for coverage of an exposed implant after skin-sparing mastectomy
      and immediate breast reconstruction.
AB  - Native skin-flap necrosis following skin-sparing mastectomy (SSM) is treated by
      raising a capsular flap, formed as a consecutive physiological reaction around
      breast implant. Using this highly vascularised thin tissue layer as an implant
      coverage withdraws pressure from the defect and allocates a good background for
      wound healing.

PMID- 20056506
TI  - Three-dimensional anthropometric analysis of the Chinese nose.
AB  - Information about normal nasal dimensions is essential to rhinoplasty, but
      reports of anthropometric measurements of the Chinese nose are limited. Three
      dimensional (3D) measuring apparatuses have been introduced into craniofacial
      anthropometry and have demonstrated advantages over conventional methods. This
      study aims to introduce a new 3D method for anthropometry and to provide guidance
      for plastic surgeons treating the Chinese nose. A total of 289 young Chinese
      adults (146 males and 143 females) were recruited for this study and a 3D stereo
      photogrammetry system (3DSS -II, Shanghai Digital Manufacturing Corporation,
      China) was used to acquire their facial image data. Geomagic Studio 10.0 software
      was used to process the data and to realign the images in a unified co-ordinate
      system. For each image, the co-ordinate values of 17 landmarks of the nose were
      collected, and the mean was calculated for males and females separately. Points
      based on the mean co-ordinate values were used to establish 3D stereo models.
      Subsequently, nasal parameters--including nine linear measurements, three angular
      measurements and seven proportions--were obtained by analysing these models. The
      3D stereo models representing the Chinese male and female nasal shapes were built
      and the nasal parameters were acquired. Some differences between male and female
      nasal shapes were identified. This study describes a new method for 3D
      anthropometric analysis of the nose; the method would be applicable to
      anthropometry of other parts of the body as well. The 3D models of Chinese noses
      built in this study will provide very useful guidance for plastic surgeons in
      clinical practice.

PMID- 20056511
TI  - Colloid transport with wetting fronts: interactive effects of solution surface
      tension and ionic strength.
AB  - Transport of colloids with transient wetting fronts represents an important
      mechanism of contaminant migration in the vadose zone. The work presented here
      used steady-state saturated and transient unsaturated flow columns to evaluate
      the transport of a fluorescent latex microsphere (980 nm in diameter) with
      capillary wetting fronts of different solution surface tensions and ionic
      strengths. The saturated transport experiments demonstrated that decreasing
      solution surface tension and ionic strength decreased colloid deposition at the
      solid-liquid interface and increased colloid recovery in the column effluent. The
      effect of solution surface tension on colloid transport and deposition was
      greater at lower ionic strength, suggesting an interaction between these two
      factors. Under transient unsaturated flow conditions, the number of colloids
      retained in sand decreased exponentially with travel distance through the porous
      media. However, lowering the solution surface tension and ionic strength resulted
      in a more even distribution of colloids along the column. The measured zeta
      potentials of colloids in different solutions suggest that both lowering surface
      tension and ionic strength would enhance the electrostatic repulsion between
      colloid and sand. The experimental results revealed that the effects are
      nonlinear, implying the possible existence of critical threshold values, beyond
      which the effects were not significant. In addition, colloid migration slowed
      down as solution surface tension decreased due to reduction of capillary forces
      that drove liquid movement.

PMID- 20056512
TI  - Effects of integrated fixed film activated sludge media on activated sludge
      settling in biological nutrient removal systems.
AB  - Integrated fixed film activated sludge (IFAS) is an increasingly popular
      modification of conventional activated sludge, consisting of the addition of
      solid media to bioreactors to create hybrid attached/suspended growth systems.
      While the benefits of this technology for improvement of nitrification and other
      functions are well-demonstrated, little is known about its effects on biomass
      settleability. These effects were evaluated in parallel, independent wastewater
      treatment trains, with and without IFAS media, both at the pilot (at two solids
      residence times) and full scales. While all samples demonstrated good
      settleability, the Control (non-IFAS) systems consistently demonstrated small but
      significant (p<0.05) improvements in settleability relative to the IFAS trains.
      Differences in biomass densities were identified as likely contributing factors,
      with Control suspended phase density>IFAS suspended phase density>IFAS attached
      phase (biofilm) density. Polyphosphate content (as non-soluble phosphorus) was
      well-correlated with density. This suggested that the attached phases had
      relatively low densities because of their lack of anaerobic/aerobic cycling and
      consequent low content of polyphosphate-accumulating organisms, and that
      differences in enhanced biological phosphorus removal performance between the
      IFAS and non-IFAS systems were likely related to the observed differences in
      density and settleability for the suspended phases. Decreases in solids retention
      times from 8 to 4 days resulted in improved settleability and increased density
      in all suspended phases, which was related to increased phosphorus content in the
      biomass, while no significant changes in density and phosphorus content were
      observed in attached phases.

PMID- 20056513
TI  - Multifunctional biomagnetic capsules for easy removal of phenol and bisphenol A.
AB  - This paper reports fabrication, optimization and characterization of
      multifunctional biocapsules with immobilized enzyme using a layer-by-layer
      configuration and their application for removal of phenol and bisphenol A (BPA).
      The method is based on the combined use of enzymatic oxidation of the BPA and
      subsequent binding of the reaction product onto a chitosan core biopolymer. This
      platform has multiple functions including: (1) enzymatic degradation of BPA, (2)
      adsorption of the degraded compound within the core material, (3) colorimetric
      quantification and (4) magnetic capabilities. We examined various configurations
      of core/shell structures of alginate and chitosan and determined the stability
      and the optimum conditions in which these structures provide the most effective
      removal capacity. The amount of BPA that can be removed per capsule is 5.6 ppm
      while phenol can be removed up to 10 ppm per capsule within 15 h.

PMID- 20056514
TI  - Characterization of active site residues of nitroalkane oxidase.
AB  - The flavoenzyme nitroalkane oxidase catalyzes the oxidation of primary and
      secondary nitroalkanes to the corresponding aldehydes and ketones plus nitrite.
      The structure of the enzyme shows that Ser171 forms a hydrogen bond to the flavin
      N5, suggesting that it plays a role in catalysis. Cys397 and Tyr398 were
      previously identified by chemical modification as potential active site residues.
      To more directly probe the roles of these residues, the S171A, S171V, S171T,
      C397S, and Y398F enzymes have been characterized with nitroethane as substrate.
      The C397S and Y398 enzymes were less stable than the wild-type enzyme, and the
      C397S enzyme routinely contained a substoichiometric amount of FAD. Analysis of
      the steady-state kinetic parameters for the mutant enzymes, including deuterium
      isotope effects, establishes that all of the mutations result in decreases in the
      rate constants for removal of the substrate proton by approximately 5-fold and
      decreases in the rate constant for product release of approximately 2-fold. Only
      the S171V and S171T mutations alter the rate constant for flavin oxidation. These
      results establish that these residues are not involved in catalysis, but rather
      are required for maintaining the protein structure.

PMID- 20056515
TI  - Contribution of fulvic acid to the photochemical formation of Fe(II) in acidic
      Suwannee River fulvic acid solutions.
AB  - We investigated the contribution of fulvic acid to the photoformation of Fe(II)
      using aqueous Suwannee River fulvic acid (SRFA) as a surrogate for the humic-like
      substances (HULIS) found in atmospheric condensed phases. The effects of pH (3.2,
      4.1, and 5.0) and wavelength (313, 334, 366, and 405nm) on Fe(II) photoformation
      were studied using monochromatic radiation at 20 degrees C. We calculated the
      wavelength-dependent Fe(II) photoformation efficiency values ("E-value"), defined
      here as a weighted sum of the product of the quantum yield and molar absorptivity
      of each Fe(II)-forming chemical species, and found that the E-values of acidic
      SRFA solutions were similar to those of Fe(OH)(2+). In addition, a comparison
      showed that the acidic SRFA solutions did not form Fe(II) fast enough to account
      for the observed Fe(II) formation efficiencies of the aqueous extracts of
      authentic aerosol samples. It was observed that 17-73% of Fe(III) had been
      reduced to Fe(II) in the dark in acidic SRFA solutions with added Fe(III) ranging
      from 0.5 to 10muM. The results of this study suggest that HULIS is unlikely to be
      the major reducing ligand in the process of photochemical formation of Fe(II) in
      acidic atmospheric drops. However, HULIS could reduce Fe(III) to Fe(II) in the
      dark, which in turn, could be important for night-time ()OH formation via the
      reaction between Fe(II) and H(2)O(2) (the Fenton reaction).

PMID- 20056516
TI  - Brief report: emotion regulation and coping as moderators in the relationship
      between personality and self-injury.
AB  - Self-injury without conscious suicidal intent is an increasingly prevalent
      phenomenon particularly among adolescent populations. This pilot study examined
      the extent and correlates of self-injurious behaviour in a school population
      sample of 393 adolescents (aged 13-18 years) using a self-report questionnaire.
      Specifically, we aimed to determine whether personality was related to self
      injury and whether this relationship was moderated by emotion regulation or
      coping strategies. Few personality and coping variables were directly related to
      self-injury after controlling for age and psychopathology. However the
      relationship between personality and self-injury was moderated by coping skills
      and emotion regulation. We suggest future research explore these relationships in
      order to determine the role of coping skills and emotional regulation training in
      prevention of self-injury.

PMID- 20056518
TI  - QSAR study of isatin analogues as in vitro anti-cancer agents.
AB  - Quantitative structure activity relationships (QSAR) of anti-cancer isatin
      derivatives were discovered by multiple linear regressions (MLR) and genetic
      algorithm partial least squares (GA-PLS) methods. Topological, chemical,
      geometrical and functional groups descriptors were found to be effective
      parameters on the cytotoxic activity. The positive effects of the number of
      halogen atoms and the number of total secondary carbons, and the negative effects
      of the number of secondary amides, and the number of ketones on the anti-cancer
      activity were in agreement with previous SAR studies. Hansch analysis showed the
      importance of lipophilic R(3) and R(5) substituents. Between MLR and GA-PLS, MLR
      represented superior results with a high statistical quality (R(2)=0.92 and
      Q(2)=0.90) for predicting the activity of the compounds.

PMID- 20056517
TI  - Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for
      bone defect repair.
AB  - Healing large bone defects and non-unions remains a significant clinical problem.
      Current treatments, consisting of auto and allografts, are limited by donor
      supply and morbidity, insufficient bioactivity and risk of infection.
      Biotherapeutics, including cells, genes and proteins, represent promising
      alternative therapies, but these strategies are limited by technical roadblocks
      to biotherapeutic delivery, cell sourcing, high cost, and regulatory hurdles. In
      the present study, the collagen-mimetic peptide, GFOGER, was used to coat
      synthetic PCL scaffolds to promote bone formation in critically-sized segmental
      defects in rats. GFOGER is a synthetic triple helical peptide that binds to the
      alpha(2)beta(1) integrin receptor involved in osteogenesis. GFOGER coatings
      passively adsorbed onto polymeric scaffolds, in the absence of exogenous cells or
      growth factors, significantly accelerated and increased bone formation in non
      healing femoral defects compared to uncoated scaffolds and empty defects. Despite
      differences in bone volume, no differences in torsional strength were detected
      after 12 weeks, indicating that bone mass but not bone quality was improved in
      this model. This work demonstrates a simple, cell/growth factor-free strategy to
      promote bone formation in challenging, non-healing bone defects. This biomaterial
      coating strategy represents a cost-effective and facile approach, translatable
      into a robust clinical therapy for musculoskeletal applications.

PMID- 20056519
TI  - Synthesis, cytotoxicity, antiviral activity and interferon inducing ability of 6
      (2-aminoethyl)-6H-indolo[2,3-b]quinoxalines.
AB  - New 6-(2-aminoethyl)-6H-indolo[2,3-b]quinoxalines were synthesized with high
      yields using bromoethylisatin and 6-(2-bromoethyl)-6H-indolo[2,3-b]quinoxaline as
      intermediates. These compounds were screened for the cytotoxicity, antiviral
      activity and interferon inducing ability. It was shown, that tested 6-(2
      aminoethyl)-6H-indolo[2,3-b]quinoxalines are low toxic potent interferon inducers
      and antivirals. Morpholine and 4-methyl-piperidine derivatives appeared as the
      most active antivirals and the least cytotoxic in the investigated series.

PMID- 20056520
TI  - Synthesis, characterization and biological evaluation of some thiourea
      derivatives bearing benzothiazole moiety as potential antimicrobial and
      anticancer agents.
AB  - Five series of thiourea derivatives bearing benzothiazole moiety (20 compounds)
      were efficiently synthesized and evaluated for antimicrobial and anticancer
      activities. The results indicated that the compounds possessed a broad spectrum
      of activity against the tested microorganisms and showed higher activity against
      fungi than bacteria. Compounds 1b, 2b, 3b, 4b and 5b exhibited the greatest
      antimicrobial activity. Preliminary study of the structure-activity relationship
      revealed that electronic factors in benzothiazole rings had a great effect on the
      antimicrobial activity of these compounds. In preliminary MTT cytotoxicity
      studies, the thiourea derivatives (2d, 5c and 5d) were found most potent. In MCF
      7 and HeLa cells, the IC(50) values were observed in the range of 18-26 microM
      and 38-46 microM, respectively.

PMID- 20056521
TI  - The plausibility of sugar addiction and its role in obesity and eating disorders.
AB  - BACKGROUND & AIMS: To consider the hypothesis that addiction to food, or more
      specifically sucrose, plays a role in obesity and eating disorders. METHODS: By
      considering the relevant literature a series of predictions were examined,
      derived from the hypothesis that addiction to sucrose consumption can develop.
      Fasting should increase food cravings, predominantly for sweet items; cravings
      should occur after an overnight fast; the obese should find sweetness
      particularly attractive; a high-sugar consumption should predispose to obesity.
      More specifically predictions based on the hypothesis that addiction to sugar is
      central to bingeing disorders were developed. Dieting should predate the
      development of bingeing; dietary style rather than psychological, social and
      economic factors should be predispose to eating disorders; sweet items should be
      preferentially consumed while bingeing; opioid antagonists should cause
      withdrawal symptoms; bingeing should develop at a younger age when there is a
      greater preference for sweetness. RESULTS: The above predications have in common
      that on no occasion was the behaviour predicted by an animal model of sucrose
      addiction supported by human studies. CONCLUSION: There is no support from the
      human literature for the hypothesis that sucrose may be physically addictive or
      that addiction to sugar plays a role in eating disorders.

PMID- 20056522
TI  - Effect of ambient-level gas-phase peroxides on foliar injury, growth, and net
      photosynthesis in Japanese radish (Raphanus sativus).
AB  - To investigate the effects of ambient-level gas-phase peroxides concurrent with
      O(3) on foliar injury, photosynthesis, and biomass in herbaceous plants, we
      exposed Japanese radish (Raphanus sativus) to clean air, 50 ppb O(3), 100 ppb
      O(3), and 2-3 ppb peroxides + 50 ppb O(3) in outdoor chambers. Compared with
      exposure to 100 ppb O(3), exposure to 2-3 ppb peroxides + 50 ppb O(3) induced
      greater damage in foliar injury, net photosynthetic rates and biomass; the
      pattern of foliar injury and the cause of net photosynthetic rate reduction also
      differed from those occurring with O(3) exposure alone. These results indicate
      for the first time that sub-ppb peroxides + 50 ppb O(3) can cause more severe
      damage to plants than 100 ppb O(3), and that not only O(3), but also peroxides,
      could be contributing to the herbaceous plant damage and forest decline observed
      in Japan's air-polluted urban and remote mountains areas.

PMID- 20056523
TI  - Combining sap flow and eddy covariance approaches to derive stomatal and non
      stomatal O3 fluxes in a forest stand.
AB  - Stomatal O3 fluxes to a mixed beech/spruce stand (Fagus sylvatica/Picea abies) in
      Central Europe were determined using two different approaches. The sap flow
      technique yielded the tree-level transpiration, whereas the eddy covariance
      method provided the stand-level evapotranspiration. Both data were then converted
      into stomatal ozone fluxes, exemplifying this novel concept for July 2007. Sap
      flow-based stomatal O3 flux was 33% of the total O3 flux, whereas derivation from
      evapotranspiration rates in combination with the Penman-Monteith algorithm
      amounted to 47%. In addition to this proportional difference, the sap flow-based
      assessment yielded lower levels of stomatal O3 flux and reflected stomatal
      regulation rather than O3 exposure, paralleling the daily courses of canopy
      conductance for water vapor and eddy covariance-based total stand-level O3 flux.
      The demonstrated combination of sap flow and eddy covariance approaches supports
      the development of O3 risk assessment in forests from O3 exposure towards flux
      based concepts.

PMID- 20056524
TI  - Race disparities in low birth weight in the U.S. South and the rest of the
      nation.
AB  - There are well-documented and as yet unexplained disparities in birth outcomes by
      race in the USA. This paper examines the sources of disparities in low birth
      weight between blacks and whites in the US, by focusing on differences in
      disparities between two very distinct geographic areas, the Deep South and the
      rest of the country. Two findings from prior research drive the analyses: first,
      health overall is worse in the Deep South states; second, race disparities are
      smaller in the Deep South than in the rest of the nation. A number of potential
      explanations for these findings are examined using nationally representative data
      on approximately 8,000 children born in the US in 2001. Results suggest that,
      first, almost all of the increased burden of low birth weight in the Deep South
      states may be explained by differences in race composition and socioeconomic
      status between the Deep South and rest of the nation. Second, the slightly lower
      race disparities found in the Deep South states are being driven not by better
      outcomes for black mothers, but by two other factors: higher returns to
      socioeconomic status for black mothers and much worse outcomes for poor white
      mothers in the Deep South compared with the rest of the country.

PMID- 20056525
TI  - On the prohibition of conflicts of interest in pharmaceutical regulation:
      precautionary limits and permissive challenges. A commentary on Sismondo (66:9,
      2008, 1909-14) and O'Donovan and Lexchin.

PMID- 20056526
TI  - A methodology for creating greenways through multidisciplinary sustainable
      landscape planning.
AB  - This research proposes a methodology for defining greenways via sustainable
      planning. This approach includes the analysis and discussion of culture and
      natural processes that occur in the landscape. The proposed methodology is
      structured in three phases: eco-cultural analysis; synthesis and diagnosis; and
      proposal. An interdisciplinary approach provides an assessment of the
      relationships between landscape structure and landscape dynamics, which are
      essential to any landscape management or land use. The landscape eco-cultural
      analysis provides a biophysical, dynamic (geomorphologic rate), vegetation
      (habitats from directive 92/43/EEC) and cultural characterisation. The knowledge
      obtained by this analysis then supports the definition of priority actions to
      stabilise the landscape and the management measures for the habitats. After the
      analysis and diagnosis phases, a proposal for the development of sustainable
      greenways can be achieved. This methodology was applied to a study area of the
      Azambuja Municipality in the Lisbon Metropolitan Area (Portugal). The application
      of the proposed methodology to the study area shows that landscape stability is
      crucial for greenway users in order to appreciate the landscape and its natural
      and cultural elements in a sustainable and healthy way, both by cycling or by
      foot. A balanced landscape will increase the value of greenways and in return,
      they can develop socio-economic activities with benefits for rural communities.

PMID- 20056527
TI  - Evaluation of spatial and temporal variation in water quality by pattern
      recognition techniques: A case study on Jajrood River (Tehran, Iran).
AB  - In this paper, principal component analysis (PCA) and hierarchical cluster
      analysis (CA) methods have been used to investigate the water quality of Jajrood
      River (Iran) and to assess and discriminate the relative magnitude of
      anthropogenic and "natural" influences on the quality of river water. T, EC, pH,
      TDS, NH(4), NO(3), NO(2), Turb., T.Hard., Ca, Mg, Na, K, Cl, SO(4), SiO(2) as
      physicochemical and TC, FC as biochemical variables have been analyzed in the
      water samples collected every month over a three-year period from 18 sampling
      stations along a 50 km section of Jajrood River that is under the influence of
      anthropogenic and natural changes. Exploratory analysis of experimental data has
      been carried out by means of PCA and CA in an attempt to discriminate sources of
      variation in water quality. PCA has allowed identification of a reduced number of
      mean 5 varifactors, pointing out 85% of both temporal and spatial changes. CA
      classified similar water quality stations and indicated Out-Meygoon as the most
      polluted one. Ahar, Baghgol, Rooteh, Befor Zaygan, Fasham, Roodak and Lashgarak
      were identified as affected by organic pollution. A Scree plot of stations in the
      first and second extracted components on PCA also gave us a classification of
      stations due to the similarity of pollution sources. CA and PCA led to similar
      results, though Out-Meygoon was identified as the most polluted station in both
      methods. Box-plots showed that PCA could approximately demonstrate temporal and
      spatial variations. CA gave us an overview of the problem and helped us to
      classify and better explain the PCA results.

PMID- 20056528
TI  - Moscatilin, a bibenzyl derivative from the India orchid Dendrobrium loddigesii,
      suppresses tumor angiogenesis and growth in vitro and in vivo.
AB  - Attacking angiogenesis is considered an effective strategy for controls the
      expansion and metastasis of tumors and other related-diseases. The aim of this
      study was to assess the effects of moscatilin, a bibenzyl derivative, on VEGF and
      bFGF-induced angiogenesis in cultured human umbilical vein endothelial cells
      (HUVECs) in vitro and in vivo. Moscatilin significantly inhibited growth of lung
      cancer cell line A549 (NSCLC) and suppressed growth factor-induced
      neovascularization. In addition, VEGF- and bFGF-induced cell proliferation,
      migration, and tube formation of HUVECs was markedly inhibited by moscatilin.
      Western blotting analysis of cell signaling molecules indicated that moscatilin
      inhibited ERK1/2, Akt, and eNOS signaling pathways in HUVECs. These results
      suggest that inhibition of angiogenesis by moscatilin may be a major mechanism in
      cancer therapy.

PMID- 20056529
TI  - Phase change material for efficient removal of crystal violet dye.
AB  - Hazardous dye removal and recovery from wastewater requires efficient capturing
      material. We report a phase change material (PCM) with phase change temperature
      of 16 degrees C giving up to 98% removal of crystal violet in few minutes. The
      PCM was found to collect 54 times of its weight soluble dye. The dye adsorption
      kinetics obeys a second order pseudo rate. Upon cooling the PCM to below 16
      degrees C it gels and enabled solid removal of the captured dye.

PMID- 20056530
TI  - The involvement of the transient receptor potential A1 (TRPA1) in the maintenance
      of mechanical and cold hyperalgesia in persistent inflammation.
AB  - This study investigated the role of TRPA1 in the development and maintenance of
      mechanical and cold hyperalgesia in persistent inflammation induced by Complete
      Freund's Adjuvant (CFA) in mice. The intraplantar (i.pl.) injection of CFA
      induced a long lasting (28 days) hyperalgesia for both mechanical and thermal
      (cold) stimuli. The intraperitoneal (i.p., 30-300 mg/kg), intraplantar (i.pl.,
      100 microg/site) or intrathecal (i.t., 10 microg/site) injection of the TRPA1
      selective antagonist HC-030031 significantly reduced the mechanical hyperalgesia
      evaluated by the von Frey hair test. The effect of HC-030031 was evidenced on the
      day after CFA injection and was kept throughout the test. However, the
      intracerebroventricular (i.c.v., 10 microg/site) injection of HC-030031 did not
      interfere with CFA-induced hyperalgesia. Treatment with HC-030031 (300 mg/kg,
      i.p.) completely inhibited the noxious cold hyperalgesia induced by
      tetrafluoroethane in mice that received CFA. The pre-treatment with the TRPA1
      oligonucleotide antisense (AS-ODN, i.t.) consistently prevented both mechanical
      and cold hyperalgesia. Interestingly, both TRPA1 protein expression and mRNA were
      over-expressed in spinal cord and dorsal root ganglia (DRG) of mice treated with
      CFA, an effect that was fully prevented by the pre-treatment with the TRPA1
      antagonist HC-030031. Collectively, the present results showed that TRPA1 present
      at either peripheral or spinal sites play a relevant role in the development and
      maintenance of both mechanical and cold hyperalgesia during CFA-induced
      inflammation. Thus, TRPA1 selective antagonists represent promising candidates to
      treat hyperalgesia in persistent inflammatory states.

PMID- 20056531
TI  - Influenza pandemics, solar activity cycles, and vitamin D.
AB  - There is historic evidence that influenza pandemics are associated with solar
      activity cycles (the Schwabe-cycle of about 11-years periodicity). The hypothesis
      is presented and developed that influenza pandemics are associated with solar
      control of vitamin D levels in humans which waxes and wanes in concert with solar
      cycle dependent ultraviolet radiation. It is proposed that this solar cycle
      dependence arises both directly from cyclic control of the amount of ultraviolet
      radiation as well as indirectly through cyclic control of atmospheric circulation
      and dynamics.

PMID- 20056532
TI  - Theophylline-induced changes in mouse electroencephalograms.
AB  - Theophylline can induce life-threatening seizures in humans, especially in
      infants, but the mechanism of induction remains unknown. We investigated the
      effects of orally administered theophylline on mouse electroencephalograms
      (EEGs). ddY mice, which are generally completely free of seizures, were used for
      the experiments. While EEGs, used as controls, showed no paroxysmal spike
      discharges, theophylline induced clear spike discharges. This study demonstrated
      that theophylline administered at doses that achieve low serum concentrations can
      cause spike discharges in mouse EEGs even without causing clinical seizures,
      indicating that theophylline plays a potent role in subclinical epileptogenicity.

PMID- 20056533
TI  - The epidemiology of Graves' disease: evidence of a genetic and an environmental
      contribution.
AB  - Previous family and twin studies have indicated that Graves' disease has a
      heritable component. Family studies have also shown that some autoimmune disease
      cluster in families and genetic studies have been able to show shared
      susceptibility genes. In the present nation-wide study we describe familial risk
      for Graves' disease among parents and offspring, singleton siblings, twins and
      spouses with regard to age of onset, gender and number and type of affected
      family members. Additionally familial association of Graves' disease with any of
      33 other autoimmune and related conditions was analyzed. The Swedish
      Multigeneration Register on 0-75-year-old subjects was linked to the Hospital
      Discharge Register from years 1987-2007. Standardized incidence ratios (SIRs)
      were calculated for individuals whose relatives were hospitalized for Graves'
      disease compared to those whose relatives were unaffected. The total number of
      hospitalized Graves' patients was 15,743. Offspring with an affected family
      member constituted 3.6% of all patients among offspring. The familial SIR was
      5.04 for individuals whose sibling was affected but it increased to 310 when two
      or more siblings were affected; the SIR in twins was 16.45. Familial risks were
      higher for males than for females. The SIR was increased to 6.22 or 30.20 when
      parental age was limited to 50 or 20 years, respectively. Graves' disease
      associated with 19 other autoimmune and related conditions, including Addison's
      disease, type 1 diabetes mellitus, Hashimoto/hypothyroidism, pernicious anemia,
      polymyositis/dermatomyositis, myasthenia gravis, discoid lupus erythematosus and
      localized scleroderma. Remarkably, there was a high disease concordance of 2.75
      between spouses. The clustering between spouses suggests environmental effects on
      Graves' disease which may contribute to the observed gender effects. The
      demonstrated high risks should be considered in clinical counseling and in
      prevention plans.

PMID- 20056534
TI  - Geo-epidemiology and autoimmunity.
AB  - Autoimmune disease (AD) affects approximately 3% of the population. This is an
      enormous number, but ironically the study of autoimmunity has not taken on the
      significance of many other diseases because so many of the ADs are relatively
      uncommon. Indeed, despite enormous advances in the diagnosis and the treatment of
      AD, there is still a paucity of data on the etiological events that lead to the
      clinical pathology. For most other human diseases, the etiology is addressed and
      often solved by the use of epidemiology. Epidemiology consists of the study of
      prevalence of a disease, coupled with analysis of genetic factors and detection
      of environmental agents. In the context of autoimmune conditions, preclinical
      epidemiology has recently been favored, as a consequence of the discovery that
      autoantibody precedes overt disease. The idea of a North-South gradient in the
      prevalence of ADs, with a reciprocal gradient in that of infectious injuries has
      proven to be debatable. More importantly, environmentally-induced changes have
      been shown to modify certain diseases giving rise to the key concept of
      epigenetics. However, it is clear that major voids exist. Some of these voids
      were hoped to be solved by the use of genome-wide associations. This, however,
      has proven very problematic, as the genetic basis of AD is considerably more
      complicated than once believed. We now base our hopes on next generational
      sequencing as a brut force undertaking to partially decipher the genetic code
      that predisposes individuals to AD. This volume is a compilation of papers in
      Autoimmunity Reviews and the Journal of Autoimmunity and presented as part of the
      7th International Congress on Autoimmunity in Ljubljana, Slovenia. It is clearly
      impossible to present data on the geoepidemiology of all of the AD. Instead, we
      attempted to generate interest amongst immunologists to generate papers that are
      thought provoking but also contemporary reviews.

PMID- 20056535
TI  - Development of on-line measurement techniques for siloxanes and other trace
      compounds in biogas.
AB  - This paper focuses on the development of an on-line measurement method for
      siloxanes and other biogas trace compounds impeding the energy utilisation of
      biogas, as well as the main gas components, methane and carbon dioxide. The
      method is based on gas chromatography and FT-IR-analysis. The level of siloxane,
      hydrogen sulphide and halogens in biogas generated in a number of landfills and
      digesters in Finland is also presented and factors affecting the concentrations
      discussed. Generally, the level of biogas trace compounds hampering electricity
      production was lower than those measured at comparable sites in Central Europe
      and the US. Moreover, the paper discusses the significance of on-line monitoring
      of siloxane in connection to biogas-to-electricity applications and points out
      with activated carbon as an example the benefits of on-line siloxane measurement
      in the control of siloxane removal technology.

PMID- 20056536
TI  - Therapeutic indications in oncology: emerging features and regulatory dynamics.
AB  - The regulatory route leading to the definition of therapeutic indications of new
      compounds as well as extensions of indication (EoI) of already approved ones is a
      challenging process. If new anticancer drugs reach the market with a lack of
      complete evidence, this usually leads regulators to request additional data, post
      approval commitments or restrictions in therapeutic indications. This study aims
      at quantifying the time needed for anticancer drugs approved by the EMEA to get
      an extension, the rates and characteristics of extensions approved, and at
      exploring the regulatory process leading to the definition of new indications. A
      total of 103 therapeutic oncological indications, related to a cohort of 43
      anticancer drugs, were retrieved between 1995 and 2008. The median time occurring
      between different indications for the same compound (defined as Time to New
      Extension, TtNE) significantly decrease from about 81 months in 1996 to 6 months
      in 2006. Twenty-four out of 43 approved anticancer medicines (about 56%) have
      only a single therapeutic indication, 12 of which were approved before 2005. When
      considering two different cohorts of drugs in relation to the time of approval
      (1995-2004 versus 2005-2008), although not statistically significant, the older
      cohort tended to have a decreased probability of having EoI when compared to the
      new cohort (OR=0.27; 95% confidence interval (CI): 0.07-1.04). With regard to the
      type of EoI (n=60), our findings showed that in 48% of cases the initially
      approved indication was extended to treat a different tumour, in 37% of cases the
      extension consisted in a switch of line within the same therapeutic indication.
      The other two types of indication broadening refer to a different tumour stage
      (8%) and to the inclusion of a new patient population (7%). The analysis of
      indication restrictions showed that in 20 cases out of 50 (40%) therapeutic
      indications were restricted by the Committee for Medicinal Products for Human Use
      (CHMP) during the assessment, with 60% of the restrictions occurring in 2006
      2007. This study adds three main pieces of information: (i) the majority of
      anticancer drugs still have a single indication regardless of the year of
      approval; (ii) the time needed to obtain an extension of indication has decreased
      significantly over the last decade and (iii) a highest rate of regulatory
      restrictions is matched to shorter clinical developments.

PMID- 20056537
TI  - Preparation of nanofibers containing the microalga Spirulina (Arthrospira).
AB  - Spirulina is a microalga which offers biological functions highly favorable for
      tissue engineering. Highly porous scaffolds can be produced by electrospinning
      containing biomass of Spirulina. The goal of this contribution was therefore to
      establish spinning conditions allowing to produce well defined nanofibers with
      diameters down to about 100 nm and to produce nanofibers with various
      concentration of the biomass for subsequent studies in tissue engineering
      applications. The experimental results reveal that the blend system PEO/biomass
      is behaved surprisingly well in electrospinning. Very thin bead-free nanofibers
      with diameters of about 110 nm can be produced for different biomass contents of
      up to 67 wt.% of the nanofibers and for PEO concentrations in the spinning
      solution well below 4 wt.%. These results suggest to us the use of the biomass
      containing nanofibers as extracellular matrices for stem cell culture and future
      treatment of spinal chord injury.

PMID- 20056538
TI  - Design, synthesis, inhibitory activity, and binding mode study of novel DNA
      methyltransferase 1 inhibitors.
AB  - To identify novel non-nucleoside DNA methyltransferase (DNMT) inhibitors, we
      designed and synthesized a series of maleimide derivatives. Among this series,
      compounds 5-8 were found to be more potent DNMT1 inhibitors than RG108, a DNMT1
      inhibitor reported previously by Siedlecki et al. The binding mode analysis of
      compound 5 is also reported.

PMID- 20056539
TI  - Investigation of Beckett-Casy model 1: synthesis of novel 16,17-seco-naltrexone
      derivatives and their pharmacology.
AB  - Novel 16,17-seco-naltrexone derivatives 3 were synthesized using a 16-17 bond
      cleavage reaction of naltrexone as the key reaction to examine the Beckett-Casy
      model. All the prepared 16,17-seco-naltrexone derivatives 3 showed lower
      affinities for opioid receptors than naltrexone. Although the results of binding
      assay seem to support the existence of a cavity in the model, further
      investigation using 15,16-nornaltrexone derivatives 26 will be needed to confirm
      the model.

PMID- 20056541
TI  - Piperidine-derived gamma-secretase modulators.
AB  - This Letter details the SAR of a novel series of piperidine-derived gamma
      secretase modulators. Compound 10h was found to be a potent modulator in vitro,
      which on further profiling, was found to decrease Abeta42, increase Abeta38 and
      have no effect on Abeta40 levels. Furthermore, 10h demonstrated excellent
      pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS
      penetration in the mouse.

PMID- 20056540
TI  - Novel bis-arylsulfonamides and aryl sulfonimides as inactivators of plasminogen
      activator inhibitor-1 (PAI-1).
AB  - Inactivators of plasminogen activator inhibitor-1 (PAI-1) have been identified as
      possible treatments for a range of conditions, including atherosclerosis, venous
      thrombosis, and obesity. We describe the synthesis and inhibitory activity of a
      novel series of compounds based on bis-arylsulfonamide and aryl sulfonimide
      motifs that show potent and specific activity towards PAI-1. Inhibitors
      containing short linking units between the sulfonyl moieties and a 3,4-dihydroxy
      aryl substitution pattern showed the most potent inhibitory activity, and
      retained high specificity for PAI-1 over the structurally-related serpin anti
      thrombin III (ATIII).

PMID- 20056542
TI  - Discovery of C-imidazole azaheptapyridine FPT inhibitors.
AB  - The discovery of C-linked imidazole azaheptapyridine bridgehead FPT inhibitors is
      described. This novel class of compounds are sub nM FPT enzyme inhibitors with
      potent cellular inhibitory activities. This series also has reduced hERG activity
      versus previous N-linked imidazole series. X-ray of compound 10a bound to FTase
      revealed strong interaction between bridgehead imidazole 3N with catalytic zinc
      atom.

PMID- 20056543
TI  - Anti-invasive and anti-angiogenic activities of naturally occurring
      dibenzodiazepine BU-4664L and its derivatives.
AB  - In the screening for antitumor leads from microbial secondary metabolites, BU
      4664L (1), a naturally occurring dibenzodiazepine, was found to inhibit tumor
      invasion and angiogenesis in vitro. Compound 1 inhibited the gelatinase
      activities of MMP-2 and MMP-9 and the cellular motility. Four derivatives (2-5)
      were synthesized from 1 and their antitumor activities were evaluated. Compounds
      3 and 4 exhibited potent anti-angiogenic effects on HUVEC, together with
      remarkable inhibition of cell migration at nanomolar concentrations, and showed
      much lower cytotoxicity.

PMID- 20056544
TI  - The effect of backbone cyclization on PK/PD properties of bioactive peptide
      peptoid hybrids: the melanocortin agonist paradigm.
AB  - A peptide-peptoid hybrid (peptomer) library was designed and synthesized, based
      on the sequence Phe-d-Phe-Arg-Trp-Gly. This sequence was previously found to
      specifically activate the melanocortin-4-receptor (MC4R) which participates in
      regulation of energy homeostasis and appetite. The library of peptomers included
      a peptoid bond in the Phe and/or d-Phe position and consisted of linear and
      backbone cyclic analogs, differed in their ring size. While the linear peptides
      rapidly degraded in serum and in brush border membrane vesicles (BBMV's), the
      linear peptomers were more stable. Backbone cyclic peptomers were also stable
      under the same conditions. Backbone cyclization significantly increased the
      intestinal permeability of two peptomers compared to their linear counterparts,
      in the Caco-2 model. Pharmacological evaluation revealed that two linear and one
      backbone cyclic peptomer, were found active towards MC4R at the nanomolar range.
      Thus, the conformational constrains imposed by these local and global
      modifications affect both the pharmacokinetic and pharmacodynamic properties of
      the parent peptide. This study demonstrates the potential of imposing backbone
      cyclization on bioactive peptomers as a promising approach in developing an
      orally available peptidomimetic drug leads.

PMID- 20056545
TI  - Quiquelignan A-H, eight new lignoids from the rattan palm Calamus
      quiquesetinervius and their antiradical, anti-inflammatory and antiplatelet
      aggregation activities.
AB  - Eight new lignin derivatives, termed quiquelignan A-H (1-8), comprising three
      tricin-type flavonolignans (1-3) and five 8-O-4' neolignans (4-8), were isolated
      from the ethanol extract of Calamus quiquesetinervius stems. Structural
      elucidation of the new isolates was accomplished on the basis of spectroscopic
      data. Compounds 1-8 showed strong-to-moderate antioxidant activity against the
      hydroxy radical (()OH). Among them, compound 5 showed significantly higher
      hydroxy radical scavenging activity (IC(50) 4.4microg/mL). Compounds 2-4 and 6-8
      dose-dependently suppressed the LPS-stimulated production of nitric oxide (NO) in
      RAW 264.7 cells. The anti-inflammatory potency of 4 and 6 was 2.7-4.5-fold higher
      compared with quercetin. Compounds 2-4, 6 and 8 also exhibited mild collagen
      antagonistic activity, but were inactive with respect to thrombin-induced
      platelet aggregation.

PMID- 20056546
TI  - 2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel
      classical and nonclassical antifolates as potential dual thymidylate synthase and
      dihydrofolate reductase inhibitors.
AB  - A novel classical antifolate N-{4-[(2,4-diamino-5-methyl-furo[2,3-d]pyrimidin-6
      yl)thio]-benzoyl}-l-glutamic acid 5 and 11 nonclassical antifolates 6-16 were
      designed, synthesized, and evaluated as inhibitors of dihydrofolate reductase
      (DHFR) and thymidylate synthase (TS). The nonclassical compounds 6-16 were
      synthesized from 20 via oxidative addition of substituted thiophenols using
      iodine. Peptide coupling of the intermediate acid 21 followed by saponification
      gave the classical analog 5. Compound 5 is the first example, to our knowledge,
      of a 2,4-diamino furo[2,3-d]pyrimidine classical antifolate that has inhibitory
      activity against both human DHFR and human TS. The classical analog 5 was a
      nanomolar inhibitor and remarkably selective inhibitor of Pneumocystis carinii
      DHFR and Mycobacterium avium DHFR at 263-fold and 2107-fold, respectively,
      compared to mammalian DHFR. The nonclassical analogs 6-16 were moderately potent
      against pathogen DHFR or TS. This study shows that the furo[2,3-d]pyrimidine
      scaffold is conducive to dual human DHFR-TS inhibitory activity and to high
      potency and selectivity for pathogen DHFR.

PMID- 20056547
TI  - Design, synthesis and in vitro characterization of Glucagon-Like Peptide-1
      derivatives for pancreatic beta cell imaging by SPECT.
AB  - Novel Glucagon-Like Peptide-1 (GLP-1) derivatives containing the metal chelator
      DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and naturally
      occurring Indium ((113/115)In) were prepared using solid-phase Fmoc methods. All
      synthesized peptides contained d-Ala-8, a modification known to improve
      resistance towards degradation by dipeptidyl peptidase-IV. The effect of
      increased distance between DOTA and the peptide chain was investigated using an
      (aminoethyl) ethoxy acetyl linker, in order to reduce steric effects imposed by
      DOTA. Placement of linker and DOTA moieties were also varied within the GLP-1
      sequence to test for optimal metal-complex location. The binding affinity of the
      peptide derivatives was determined in vitro with Chinese hamster ovary cells
      stably transfected with a human GLP-1 receptor (CHO/GLP-1R) cell line and was
      shown to be in the nM range. Gamma camera imaging of an insulinoma cell line was
      carried out using (111)In-labeled peptides. Our results suggest that the prepared
      GLP-1 derivatives are suitable imaging probes for studying pancreatic islet
      function in vivo.

PMID- 20056548
TI  - Synthesis, in vitro structure-activity relationship, and in vivo studies of 2
      arylthiazolidine-4-carboxylic acid amides as anticancer agents.
AB  - A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was
      synthesized. Antiproliferative activity against melanoma and prostate cancer
      cells compared with control cells (fibroblast and RH7777, respectively) was
      evaluated. Compound 3id showed the best selectivity and growth-inhibition
      activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds
      15b and 3ac had good selectivity and potency against four prostate cancer cell
      lines (DU 145, PC-3, LNCaP, and PPC-1). The structure-activity relationship (SAR)
      of the side chain, the thiazolidine ring, and phenyl substituents is discussed.
      Cell cycle analysis showed that the percentage of cancer cells undergoing
      apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also
      strongly inhibited melanoma colony formation. In vivo studies on nude mice
      bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a
      dose-dependent manner. At a dose of 10mg/kg, 1b significantly inhibited melanoma
      tumor growth and showed higher efficacy than did dacarbazine at 60mg/kg.

PMID- 20056549
TI  - Discovery of 3-(4-bromophenyl)-6-nitrobenzo[1.3.2]dithiazolium ylide 1,1-dioxide
      as a novel dual cyclooxygenase/5-lipoxygenase inhibitor that also inhibits tumor
      necrosis factor-alpha production.
AB  - In the present study we have discovered compound 1, a benzo[1.3.2]dithiazolium
      ylide-based compound, as a new prototype dual inhibitor of cyclooxygenase (COX)
      and 5-lipoxygenase (5-LOX). Compound 1 was initially discovered as a COX-2
      inhibitor, resulting indirectly from the COX-2 structure-based virtual screening
      that identified compound 2 as a virtual hit. Compounds 1 and 2 inhibited COX-1
      and COX-2 in mouse macrophages with IC(50) in the range of 1.5-18.1microM. Both
      compounds 1 and 2 were also found to be potent inhibitors of human 5-LOX
      (IC(50)=1.22 and 0.47microM, respectively). Interestingly, compound 1 also had an
      inhibitory effect on tumor necrosis factor-alpha (TNF-alpha) production
      (IC(50)=0.44microM), which was not observed with compound 2. Docking studies
      suggested the (S)-enantiomer of 1 as the biologically active isomer that binds to
      COX-2. Being a cytokine-suppressive dual COX/5-LOX inhibitor, compound 1 may
      represent a useful lead structure for the development of advantageous new anti
      inflammatory agents.

PMID- 20056550
TI  - Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine,
      N,N'-diacetylchitobiose and N-acetyllactosamine: Analysis of cross-linking
      activities with WGA and ECA lectins.
AB  - Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N
      acetylglucosamine (GlcNAc), N,N'-diacetylchitobiose [(GlcNAc)(2)] and N
      acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The
      interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree
      (Erythrina cristagalli) agglutinin (ECA) with a series of tetravalent glycosides
      and related compounds were studied using a hemagglutination inhibition assay, a
      precipitation assay, double-diffusion test, and an optical biosensor based on
      surface plasmon resonance (SPR). The tetravalent glycosides were found to be
      capable of binding and precipitating the lectins as tetravalent ligands. Strong
      interactions with WGA, due to a combination of multivalency effects and spacer
      effects, were observed for tetravalent glycosides bearing flexible tandem GlcNAc.
      The chelate effect leads to large rate enhancement for the tetravalent system
      with favorable orientation of ligands. Our simple strategy produced multivalent
      glycosides with strong cross-linking activity for lectin as a specific coagulant.

PMID- 20056551
TI  - Preparation and biodistribution of [18F]FP2OP as myocardial perfusion imaging
      agent for positron emission tomography.
AB  - Myocardial extractions of pyridaben, a mitochondrial complex I (MC-I) inhibitor,
      is well correlated with blood flow. Based on the synthesis and characterization
      of pyridaben analogue 2-tert-butyl-5-[2-(2-[(18)F]fluroethoxy)ethoxy]benzyloxy]-4
      chloro-2H-pyridazin-3-one ([(18)F]FP2OP), this study assessed its potential to be
      developed as myocardial perfusion imaging (MPI) agent. METHODS: The tosylate
      labeling precursor 2-(2-(4-(tert-butyl-5-chloro-6-oxo-1,6-dihydro-pyridazin-4
      yloxymethyl)benzyloxy)ethoxy)ethyl ester (OTs-P2OP) and the nonradioactive 2-tert
      butyl-5-[2-(2-[(19)F]fluroethoxy)ethoxy]benzyloxy]-4-chloro-2H-pyridazin-3-one
      ([(19)F]FP2OP) were synthesized and characterized by IR, (1)H NMR, (13)C NMR and
      MS analysis. By substituting tosyl of precursor OTs-P2OP with (18)F, the
      radiolabeled complex [(18)F]FP2OP was prepared and further evaluated for its in
      vitro physicochemical properties, in vivo biodistribution, the metabolic
      stability in mice, ex vivo autoradiography and cardiac PET/CT imaging. RESULTS:
      Starting with [(18)F]F(-) Kryptofix 2.2.2./K(2)CO(3) solution, the total reaction
      time for [(18)F]FP2OP was about 100 min, with final high-performance liquid
      chromatography purification included. Typical decay-corrected radiochemical yield
      stayed at 41+/-5.3%, the radiochemical purity, 98% or more. Biodistribution in
      mice showed that the heart uptake of [(18)F]FP2OP was 41.90+/-4.52%ID/g at 2 min
      post-injection time, when the ratio of heart/liver, heart/lung and heart/blood
      reached 6.83, 9.49 and 35.74, respectively. Lipophilic molecule was further
      produced by metabolized [(18)F]FP2OP in blood and urine at 30 min. Ex vivo
      autoradiography demonstrates that [(18)F]FP2OP may have high affinity with MC-I
      and that can be blocked by [(19)F]FP2OP or rotenone (a known MC-I inhibitor).
      Cardiac PET images were obtained in a Chinese mini-swine at 5, 15, 30 and 60 min
      post-injection time with high quality. CONCLUSION: [(18)F]FP2OP was synthesized
      with high radiochemical yield. The promising biological properties of
      [(18)F]FP2OP suggest high potential as MPI agent for positron emission tomography
      in the future.

PMID- 20056552
TI  - Photodynamic therapy induces selective extravasation of macromolecules: Insights
      using intravital microscopy.
AB  - Photodynamic therapy (PDT) with Visudyne acts by direct cellular phototoxicity
      and/or by an indirect vascular-mediated effect. Here, we demonstrate that the
      vessel integrity interruption by PDT can promote the extravasation of a
      macromolecular agent in normal tissue. To obtain extravasation in normal tissue
      PDT conditions were one order of magnitude more intensive than the ones in tissue
      containing neovessels reported in the literature. Fluorescein isothiocyanate
      dextran (FITC-D, 2000 kDa), a macromolecular agent, was intravenously injected 10
      min before (LK0 group, n=14) or 2h (LK2 group, n=16) after Visudyne-mediated PDT
      in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL
      group, n=8). The extravasation of FITC-D from blood vessels in striated muscle
      tissue was observed in both groups in real-time for up to 2500 s after injection.
      We also monitored PDT-induced leukocyte rolling in vivo and assessed, by
      histology, the corresponding inflammatory reaction score in the dorsal skin fold
      chambers. In all animals, at the applied PDT conditions, FITC-D extravasation was
      significantly enhanced in the PDT-treated areas as compared to the surrounding
      non-treated areas (p<0.0001). There was no FITC-D leakage in the control animals.
      Animals from the LK0 group had significantly less FITC-D extravasation than those
      from the LK2 group (p=0.0002). In the LK0 group FITC-D leakage correlated
      significantly with the inflammation (p<0.001). At the selected conditions,
      Visudyne-mediated PDT promotes vascular leakage and FITC-D extravasation into the
      interstitial space of normal tissue. The intensity of vascular leakage depends on
      the time interval between PDT and FITC-D injection. This concept could be used to
      locally modulate the delivery of macromolecules in vivo.

PMID- 20056553
TI  - Hypoxic "second hit" in leukocytes from trauma patients: Modulation of the immune
      response by histone deacetylase inhibition.
AB  - INTRODUCTION: Histone deacetylase inhibitors (HDACI), can improve survival after
      lethal hemorrhagic shock, and modulate the inflammatory response after
      hemorrhage/lipopolysaccharide (LPS). The current experiments were designed to
      study the effects of HDACI after hemorrhage and severe hypoxia. METHODS: Splenic
      leukocytes from trauma and non-trauma patients (n=4-5/group) were exposed to
      severe hypoxia with/without suberoylanilide hydroxamic acid (SAHA, 400 nM) for
      8h. Cytokines were measured by ELISA and RT-PCR, and hypoxia inducible factor
      (HIF)-1a and heme oxygenase (HO)-1 by Western blot. RESULTS: After hemorrhage and
      hypoxia, SAHA increased IL-1b gene (4.7+/-1.2-fold) and protein expression (2.1+/
      0.6-fold) in trauma splenic leukocytes. It also reduced IL-10 gene expression
      (0.6+/-0.2-fold), but did not alter TNFa or IL-6 levels. This unexpected pro
      inflammatory response may be due to a decrease in HIF-1a and HO-1 protein levels.
      CONCLUSIONS: In this model of severe hypoxia, treatment with SAHA increased the
      inflammatory response in trauma leukocytes, possibly through inhibition of the
      HIF-1/HO-1 pathway. Splenic leukocytes from non-trauma patients were variably
      affected by SAHA. Taken in context with the known anti-inflammatory properties of
      HDACI after hemorrhage/LPS, these findings suggest that the immune-modulating
      functions of HDACI are dependent on the type and severity of both the priming
      injury and subsequent insult.

PMID- 20056554
TI  - Prior-entry: a review.
AB  - The law of prior entry was one of E.B. Titchener's seven fundamental laws of
      attention. According to Titchener (1908, p. 251): "the object of attention comes
      to consciousness more quickly than the objects which we are not attending to."
      Although researchers have been studying prior entry for more than a century now,
      progress in understanding the effect has been hindered by the many methodological
      confounds present in early research. As a consequence, it is unclear whether the
      behavioral effects reported in the majority of published studies in this area
      should be attributed to attention, decisional response biases, and/or, in the
      case of exogenous spatial cuing studies of the prior-entry effect, to sensory
      facilitation effects instead. In this article, the literature on the prior-entry
      effect is reviewed, the confounds present in previous research highlighted,
      current consensus summarized, and some of the key questions for future research
      outlined. In particular, recent research has now provided compelling
      psychophysical and electrophysiological evidence to support the claim that
      attending to a sensory modality, spatial location, or stimulus feature/attribute
      can all give rise to a relative speeding-up of the time of arrival of attended,
      as compared to relatively less attended (or unattended) stimuli. Prior-entry
      effects have now been demonstrated following both the endogenous and exogenous
      orienting of attention, though prior-entry effects tend to be smaller in
      magnitude when assessed by means of participants' performance on SJ tasks than
      when assessed by means of their performance on TOJ tasks.

PMID- 20056555
TI  - Comparison of subcutaneous and transdermal administration of buprenorphine for
      pre-emptive analgesia in dogs undergoing elective ovariohysterectomy.
AB  - The clinical efficacy of a 70 microg/h transdermal buprenorphine patch and of 20
      microg/kg of buprenorphine administered subcutaneously (SC) for the relief of
      post-operative pain was determined in 24 healthy female dogs undergoing elective
      ovariohysterectomy (OHE). Dogs were randomly assigned to three groups: (1) a
      control group that received no analgesics, (2) a BSC group that received
      buprenorphine SC (20 microg/kg), and (3) a BP group that received buprenorphine
      by a 70 microg/h transdermal patch. Dogs were scored for signs of pain at 0, 2,
      4, 6, 8, 10, 14, 20, 26, 32 and 38 h after extubation using the Numerical Rating
      Scale (NRS) and a modified University of Melbourne Pain Scale (UMPS). Mean NRS
      and UMPS scores for dogs in the BSC group (2.56 +/- 0.23 and 3.05 +/- 0.27,
      respectively) and the BP group (2.02 +/- 0.24 and 2.67 +/- 0.23, respectively)
      were significantly lower (P<0.05) compared with dogs in the control group (5.42
      +/- 0.38 and 7.89 +/- 0.44, respectively), whereas differences between the two
      buprenorphine treatment groups were not significant. The results indicated that
      the analgesia produced by the 70 microg/h patch was similar to that induced by SC
      administration of 20 microg/kg of buprenorphine in dogs undergoing OHE,
      suggesting that the transdermal buprenorphine patch may be a useful alternative
      for pain management in dogs.

PMID- 20056556
TI  - Equine insulin resistance: the quest for sensitivity.

PMID- 20056557
TI  - Mu-opioid receptors are not necessary for nortriptyline treatment of neuropathic
      allodynia.
AB  - Tricyclic antidepressants (TCAs) are among the first line treatments clinically
      recommended against neuropathic pain. However, the mechanism by which they
      alleviate pain is still unclear. Pharmacological and genetic approaches evidenced
      a critical role of delta-opioid receptors (DORs) in the therapeutic action of
      chronic TCA treatment. It is however unclear whether mu-opioid receptors (MORs)
      are also necessary to the pain-relieving action of TCAs. The lack of highly
      selective MOR antagonists makes difficult to conclude based on pharmacological
      studies. In the present work, we thus used a genetic approach and compared mutant
      mice lacking MORs and their wild-type littermates. The neuropathy was induced by
      unilateral sciatic nerve cuffing. The threshold for mechanical response was
      evaluated using von Frey filaments. MOR-deficient mice displayed the same
      baseline for mechanical sensitivity as their wild-type littermates. After sciatic
      nerve cuffing, both wild-type and MOR-deficient mice displayed an ipsilateral
      mechanical allodynia. After about 10 days of treatment, nortriptyline suppressed
      this allodynia in both wild-type and MOR-deficient mice. MORs are thus not
      critical for nortriptyline action against neuropathic pain. An acute injection of
      the DOR antagonist naltrindole induced a relapse of neuropathic allodynia in both
      wild-type and MOR-deficient mice, thus confirming the critical role of DORs in
      nortriptyline action. Moreover, morphine induced an acute analgesia in control
      and in neuropathic wild-type mice, but was without effect in MOR-deficient mice.
      While MORs are crucial for morphine action, they are not critical for
      nortriptyline action. Our results highlight the functional difference between
      DORs and MORs in mechanisms of pain relief.

PMID- 20056558
TI  - Neuronal hyperactivity at the spinal cord and periaqueductal grey during painful
      diabetic neuropathy: effects of gabapentin.
AB  - Painful diabetic neuropathy may be due to impairments in descending modulation of
      nociceptive transmission at the spinal cord. In the present study, streptozotocin
      diabetic rats (STZ rats) with neuropathic symptoms (mechanical hypersensitivity)
      were used to perform a time-course evaluation of neuronal activity at the spinal
      dorsal horn and at the periaqueductal grey matter (PAG), a major brainstem area
      of pain modulation. The expression of Fos protein, a marker of nociceptive
      activation, progressively increased at the spinal dorsal horn at 4 and 10 weeks.
      At the PAG, increases in Fos expression were detected until the 4th week, with a
      reversal to baseline values at 10 weeks in all areas except the ventrolateral
      PAG. Co-localisation of Fos with NeuN ascertained the neuronal nature of Fos
      expressing cells at the spinal cord and PAG. Four weeks after diabetes induction,
      the effects of gabapentin (i.p. injection of 50mg/kg, daily during 3 days) were
      assessed. Gabapentin decreased Fos expression at the spinal cord and PAG and
      reversed mechanical hypersensitivity. The present study shows that diabetic
      neuropathy is accompanied by a progressive increase of the spontaneous neuronal
      activity at the spinal cord. Changes in descending modulation of nociceptive
      transmission from the PAG are likely to occur during diabetic neuropathy,
      probably with exacerbation of facilitatory actions. The effects of gabapentin in
      reversing the behavioural signs of diabetic neuropathy and neuronal hyperactivity
      in the spinal cord and PAG reinforce the central causes of diabetic neuropathy
      and point to the central targets of the drug.

PMID- 20056559
TI  - Clinical experience with miglustat therapy in pediatric patients with Niemann
      Pick disease type C: a case series.
AB  - Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid
      storage disease characterized by progressive neurological deterioration.
      Different clinical forms have been defined based on patient age at onset:
      perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We
      evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C
      patients, with comparative reference to one neurologically asymptomatic,
      untreated patient. All patients were categorized according to age at neurological
      disease onset, and were assessed using a standardized clinical assessment
      protocol: disability and cognitive function scales, positron emission tomography
      (PET), and biochemical markers. PET and disability scale evaluations indicated
      that cerebral hypometabolism and neurological symptoms were stabilized during
      treatment in juvenile-onset NP-C patients. EI and Li NP-C patients, who had
      higher disease severity at baseline (treatment start), showed increased
      disability scores and progressive cerebral hypometabolism during follow up.
      Similarly, while cognitive scale scores remained relatively stable in patients
      with juvenile NP-C, cognition deteriorated in EI and Li patients. Plasma
      chitotriosidase (ChT) activity was lower in the juvenile NP-C subgroup than in EI
      and Li patients, and generally increased in patients who discontinued treatment.
      Plasma CCL18/PARC and ChT activities indicated greater macrophagic activity in EI
      and Li patients versus juveniles. Miglustat was generally well tolerated;
      frequent adverse events included diarrhea and flatulence, which were managed
      effectively by dietary modification and loperamide. Overall, miglustat appeared
      to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic
      benefits appeared smaller among younger patients who were at a more advanced
      stage of disease at baseline.

PMID- 20056560
TI  - Urethral length in girls with lower urinary tract symptoms and forme fruste of
      female epispadias.
AB  - PURPOSE: To investigate systematically the length of the urethra in girls with
      lower urinary tract symptoms. MATERIALS AND METHODS: In a group of 121
      consecutive girls presented at a tertiary referral clinic for urinary
      incontinence or recurrent urinary tract infections, urethral length was measured
      by perineal ultrasound. The urethra was measured with the patient in supine
      position without anesthesia. Mean age of the patients was 7.8 (0-15) years.
      RESULTS: Average urethral length was 26 mm. Minimum length was 12 mm, measured in
      a 5-year-old girl with dribbling incontinence. Maximum measured length was 40 mm
      in a 15-year-old girl. In four girls (3.3%), aged 1-10 years (mean 6.3), a short
      urethra was detected, with measured lengths of 12 and 14 mm. All four had normal
      genitalia, and were referred with therapy-resistant urinary incontinence or
      urinary tract infections. A gradual increase in average urethral length was
      measured from 23 mm at birth to 32 mm at 15 years. CONCLUSION: Urethral length
      can be measured accurately by ultrasound. Although a short urethral length is
      rarely detected by ultrasound in girls with incontinence, it may be associated
      with therapy-resistant incontinence. In such cases, different treatment options
      are available.

PMID- 20056561
TI  - Prenatal exposure to PBDEs and neurodevelopment.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are widely used flame
      retardant compounds that are persistent and bioaccumulative and therefore have
      become ubiquitous environment contaminants. Animal studies suggest that prenatal
      PBDE exposure may result in adverse neurodevelopmental effects. OBJECTIVE: In a
      longitudinal cohort initiated after 11 September 2001, including 329 mothers who
      delivered in one of three hospitals in lower Manhattan, New York, we examined
      prenatal PBDE exposure and neurodevelopment when their children were 12-48 and 72
      months of age. METHODS: We analyzed 210 cord blood specimens for selected PBDE
      congeners and assessed neurodevelopmental effects in the children at 12-48 and 72
      months of age; 118, 117, 114, 104, and 96 children with available cord PBDE
      measurements were assessed at 12, 24, 36, 48, and 72 months, respectively. We
      used multivariate regression analyses to evaluate the associations between
      concentrations of individual PBDE congeners and neurodevelopmental indices.
      RESULTS: Median cord blood concentrations of PBDE congeners 47, 99, and 100 were
      11.2, 3.2, and 1.4 ng/g lipid, respectively. After adjustment for potential
      confounders, children with higher concentrations of BDEs 47, 99, or 100 scored
      lower on tests of mental and physical development at 12-48 and 72 months.
      Associations were significant for 12-month Psychomotor Development Index (BDE
      47), 24-month Mental Development Index (MDI) (BDE-47, 99, and 100), 36-month MDI
      (BDE-100), 48-month full-scale and verbal IQ (BDE-47, 99, and 100) and
      performance IQ (BDE-100), and 72-month performance IQ (BDE-100). CONCLUSIONS:
      This epidemiologic study demonstrates neurodevelopmental effects in relation to
      cord blood PBDE concentrations. Confirmation is needed in other longitudinal
      studies.

PMID- 20056562
TI  - Urinary concentrations of four parabens in the U.S. population: NHANES 2005-2006.
AB  - BACKGROUND: Parabens are widely used as antimicrobial preservatives in cosmetics,
      -pharmaceuticals, and food and beverage processing. OBJECTIVES: We assessed
      exposure to methyl, ethyl, propyl, and butyl parabens in a representative sample
      of persons >or= 6 years of age in the U.S. general population from the 2005-2006
      National Health and Nutrition Examination Survey. METHODS: We analyzed 2,548
      urine samples by using online solid-phase extraction coupled to isotope dilution
      high-performance liquid chromatography/tandem mass spectrometry. RESULTS: We
      detected methyl paraben (MP) and propyl paraben (PP) in 99.1% and 92.7% of the
      samples, respectively. We detected ethyl (42.4%) and butyl (47%) parabens less
      frequently and at median concentrations at least one order of magnitude lower
      than MP (63.5 microg/L) and PP (8.7 microg/L). Least-square geometric mean (LSGM)
      concentrations of MP were significantly higher (p <or= 0.01) among non-Hispanic
      blacks than among non-Hispanic whites except at older ages (>or= 60 years).
      Adolescent and adult females had significantly higher (p < 0.01) LSGM
      concentrations of MP and PP than did adolescent and adult males. Females were
      more likely than males [adjusted odds ratios (ORs) and 95% confidence intervals
      (CIs): MP, 3.2 (2.99-5.27); PP, 4.19 (2.34-7.49)] and non-Hispanic blacks were
      more likely than non-Hispanic whites [MP, 4.99 (2.62-9.50); PP, 3.6 (1.86-7.05)]
      to have concentrations above the 95th percentile. CONCLUSIONS: The general U.S.
      population was exposed to several parabens during 2005-2006. Differences in the
      urinary concentrations of MP and PP by sex and race/ethnicity likely reflect the
      use of personal care products containing these compounds.

PMID- 20056563
TI  - Economic activity and trends in ambient air pollution.
AB  - BACKGROUND: One challenge in assessing the health effects of human exposure to
      air pollution in epidemiologic studies is the lack of widespread historical air
      pollutant monitoring data with which to characterize past exposure levels.
      OBJECTIVES: Given the availability of long-term economic data, we relate economic
      activity levels to patterns in vehicle-related particulate matter (PM) over a 30
      year period in New Jersey, USA, to provide insight into potential historical
      surrogate markers of air pollution. METHODS: We used statewide unemployment and
      county-level trucking industry characteristics to estimate historical coefficient
      of haze (COH), a marker of vehicle-related PM predominantly from diesel exhaust.
      A total of 5,920 observations were included across 25 different locations in New
      Jersey between 1971 and 2003. RESULTS: A mixed-modeling approach was employed to
      estimate the impact of economic indicators on measured COH. The model explained
      approximately 50% of the variability in COH as estimated by the overall R2 value.
      Peaks and lows in unemployment tracked negatively with similar extremes in COH,
      whereas employment in the trucking industry was positively associated with COH.
      Federal air quality regulations also played a large and significant role in
      reducing COH levels over the study period. CONCLUSIONS: This new approach
      outlines an alternative method to reconstruct historical exposures that may
      greatly aid epidemiologic research on specific causes of health effects from
      urban air pollution. Economic activity data provide a potential surrogate marker
      of changes in exposure levels over time in the absence of direct monitoring data
      for chronic disease studies, but more research in this area is needed.

PMID- 20056564
TI  - What role for biologically based dose-response models in estimating low-dose
      risk?
AB  - BACKGROUND: Biologically based dose-response (BBDR) models can incorporate data
      on biological processes at the cellular and molecular level to link external
      exposure to an adverse effect. OBJECTIVES: Our goal was to examine the utility of
      BBDR models in estimating low-dose risk. METHODS: We reviewed the utility of BBDR
      models in risk assessment. RESULTS: BBDR models have been used profitably to
      evaluate proposed mechanisms of toxicity and identify data gaps. However, these
      models have not improved the reliability of quantitative predictions of low-dose
      human risk. In this commentary we identify serious impediments to developing BBDR
      models for this purpose. BBDR models do not eliminate the need for empirical
      modeling of the relationship between dose and effect, but only move it from the
      whole organism to a lower level of biological organization. However, in doing
      this, BBDR models introduce significant new sources of uncertainty. Quantitative
      inferences are limited by inter- and intraindividual heterogeneity that cannot be
      eliminated with available or reasonably anticipated experimental techniques. BBDR
      modeling does not avoid uncertainties in the mechanisms of toxicity relevant to
      low-level human exposures. Although implementation of BBDR models for low-dose
      risk estimation have thus far been limited mainly to cancer modeled using a two
      stage clonal expansion framework, these problems are expected to be present in
      all attempts at BBDR modeling. CONCLUSIONS: The problems discussed here appear so
      intractable that we conclude that BBDR models are unlikely to be fruitful in
      reducing uncertainty in quantitative estimates of human risk from low-level
      exposures in the foreseeable future. Use of in vitro data from recent advances in
      molecular toxicology in BBDR models is not likely to remove these problems and
      will introduce new issues regarding extrapolation of data from in vitro systems.

PMID- 20056565
TI  - Association of heart rate variability in taxi drivers with marked changes in
      particulate air pollution in Beijing in 2008.
AB  - BACKGROUND: Heart rate variability (HRV), a marker of cardiac autonomic function,
      has been -associated with particulate matter (PM) air pollution, especially in
      older patients and those with cardio-vascular diseases. However, the effect of PM
      exposure on cardiac autonomic function in young, healthy adults has received less
      attention. OBJECTIVES: We evaluated the relationship between exposure to traffic
      related PM with an aerodynamic diameter <or= 2.5 microm (PM2.5) and HRV in a
      highly exposed panel of taxi drivers. METHODS: Continuous measurements of
      personal exposure to PM2.5 and ambulatory electrocardiogram monitoring were
      conducted on 11 young healthy taxi drivers for a 12-hr work shift during their
      work time (09002100 hr) before, during, and after the Beijing 2008 Olympic Games.
      Mixed-effects regression models were used to estimate associations between PM2.5
      exposure and percent changes in 5-min HRV indices after combining data from the
      three time periods and controlling for potentially confounding variables.
      RESULTS: Personal exposures of taxi drivers to PM2.5 changed markedly across the
      three time -periods. The standard deviation of normal-to-normal (SDNN) intervals
      decreased by 2.2% [95% confidence interval (CI), 3.8% to 0.6%] with an
      interquartile range (IQR; 69.5 microg/m3) increase in the 30-min PM2.5 moving
      average, whereas the low-frequency and high-frequency powers decreased by 4.2%
      (95% CI, 9.0% to 0.8%) and 6.2% (95% CI, 10.7% to 1.5%), respectively, in
      association with an IQR increase in the 2-hr PM2.5 moving average. CONCLUSIONS:
      Marked changes in traffic-related PM2.5 exposure were associated with altered
      cardiac autonomic function in young healthy adults.

PMID- 20056566
TI  - Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate
      (Tamiflu), detected in sewage discharge and river water in Japan.
AB  - BACKGROUND: Oseltamivir phosphate (OP; Tamiflu) is a prodrug of the anti
      influenza neuraminidase inhibitor oseltamivir carboxylate (OC) and has been
      developed for the treatment and prevention of both A and B strains of influenza.
      The recent increase in OP resistance in influenza A virus (H1N1; commonly called
      "swine flu") has raised questions about the widespread use of Tamiflu in seasonal
      epidemics and the potential ecotoxicologic risk associated with its use in the
      event of a pandemic. OBJECTIVES: The objectives of this study were to develop an
      analytical method for quantitative determination of OC in sewage treatment plant
      (STP) effluent and receiving river water, and to investigate the occurrence of OC
      in STP effluent and river water in Japan during a seasonal flu outbreak. METHODS:
      We developed an analytical method based on solid-phase extraction followed by
      liquid chromatography-tandem mass spectrometry. Using this method, we analyzed
      samples from three sampling campaigns conducted during the 2008-2009 flu season
      in Kyoto City, Japan. RESULTS: The highest concentration of OC detected in STP
      discharge was 293.3 ng/L from a conventional activated-sludge-based STP; however,
      we detected only 37.9 ng/L from an advanced STP with ozonation as a tertiary
      treatment. In the receiving river water samples, we detected 6.6-190.2 ng/L OC,
      during the peak of the flu season. CONCLUSION: OC is present in STP effluent and
      river water only during the flu season. Ozonation as tertiary treatment in STP
      will substantially reduce the OC load in STP effluent during an influenza
      epidemic or pandemic.

PMID- 20056567
TI  - Childhood brain tumors, residential insecticide exposure, and pesticide
      metabolism genes.
AB  - BACKGROUND: Insecticides that target the nervous system may play a role in the
      development of childhood brain tumors (CBTs). Constitutive genetic variation
      affects metabolism of these chemicals. METHODS: We analyzed population-based case
      control data to examine whether CBT is associated with the functional genetic
      polymorphisms PON1C-108T, PON1Q192R, PON1L55M, BCHEA539T, FMO1C-9536A, FMO3E158K,
      ALDH3A1S134A, and GSTT1 (null). DNA was obtained from newborn screening archives
      for 201 cases and 285 controls, <or= 10 years of age, and born in California or
      Washington State between 1978 and 1990. Conception-to-diagnosis home insecticide
      treatment history was ascertained by interview. RESULTS: We observed no
      biologically plausible main effects for any of the metabolic polymorphisms with
      CBT risk. However, we observed strong interactions between genotype and
      insecticide exposure during childhood. Among exposed children, CBT risk increased
      per PON1-108T allele [odds ratio (OR) = 1.8; 95% confidence interval (CI), 1.1
      3.0] and FMO1-9536A (*6) allele (OR = 2.7; 95% CI, 1.2-5.9), whereas among
      children never exposed, CBT risk was not increased (PON1: OR = 0.7; 95% CI, 0.5
      1.0, interaction p = 0.005; FMO1: OR = 1.0; 95% CI, 0.6-1.6, interaction p =
      0.009). We observed a similar but statistically nonsignificant interaction
      between childhood exposure and BCHEA539T (interaction p = 0.08). These
      interactions were present among both Hispanic and non-Hispanic white children.
      CONCLUSION: Based on known effects of these variants, these results suggest that
      exposure in childhood to organophosphorus and perhaps to carbamate insecticides
      in combination with a reduced ability to detoxify them may be associated with
      CBT. Confirmation in other studies is required.

PMID- 20056568
TI  - A qualitative meta-analysis reveals consistent effects of atrazine on freshwater
      fish and amphibians.
AB  - OBJECTIVE: The biological effects of the herbicide atrazine on freshwater
      vertebrates are highly controversial. In an effort to resolve the controversy, we
      conducted a qualitative meta-analysis on the effects of ecologically relevant
      atrazine concentrations on amphibian and fish survival, behavior, metamorphic
      traits, infections, and immune, endocrine, and reproductive systems. DATA
      SOURCES: We used published, peer-reviewed research and applied strict quality
      criteria for inclusion of studies in the meta-analysis. DATA SYNTHESIS: We found
      little evidence that atrazine consistently caused direct mortality of fish or
      amphibians, but we found evidence that it can have indirect and sublethal
      effects. The relationship between atrazine concentration and timing of amphibian
      metamorphosis was regularly nonmonotonic, indicating that atrazine can both
      accelerate and delay metamorphosis. Atrazine reduced size at or near
      metamorphosis in 15 of 17 studies and 14 of 14 species. Atrazine elevated
      amphibian and fish activity in 12 of 13 studies, reduced antipredator behaviors
      in 6 of 7 studies, and reduced olfactory abilities for fish but not for
      amphibians. Atrazine was associated with a reduction in 33 of 43 immune function
      end points and with an increase in 13 of 16 infection end points. Atrazine
      altered at least one aspect of gonadal morphology in 7 of 10 studies and
      consistently affected gonadal function, altering spermatogenesis in 2 of 2
      studies and sex hormone concentrations in 6 of 7 studies. Atrazine did not affect
      vitellogenin in 5 studies and increased aromatase in only 1 of 6 studies. Effects
      of atrazine on fish and amphibian reproductive success, sex ratios, gene
      frequencies, populations, and communities remain uncertain. CONCLUSIONS: Although
      there is much left to learn about the effects of atrazine, we identified several
      consistent effects of atrazine that must be weighed against any of its benefits
      and the costs and benefits of alternatives to atrazine use.

PMID- 20056569
TI  - Blood mercury concentrations in CHARGE Study children with and without autism.
AB  - BACKGROUND: Some authors have reported higher blood mercury (Hg) levels in
      persons with autism, relative to unaffected controls. OBJECTIVES: We compared
      blood total Hg concentrations in children with autism or autism spectrum disorder
      (AU/ASD) and typically developing (TD) controls in population-based samples, and
      determined the role of fish consumption in differences observed. METHODS: The
      Childhood Autism Risk from Genetics and the Environment (CHARGE) Study enrolled
      children 2-5 years of age. After diagnostic evaluation, we analyzed three groups:
      AU/ASD, non-AU/ASD with developmental delay (DD), and population-based TD
      controls. Mothers were interviewed about household, medical, and dietary
      exposures. Blood Hg was measured by inductively coupled plasma mass spectrometry.
      Multiple linear regression analysis was conducted (n = 452) to predict blood Hg
      from diagnostic status controlling for Hg sources. RESULTS: Fish consumption
      strongly predicted total Hg concentration. AU/ASD children ate less fish. After
      adjustment for fish and other Hg sources, blood Hg levels in AU/ASD children were
      similar to those of TD children (p = 0.75); this was also true among non-fish
      eaters (p = 0.73). The direct effect of AU/ASD diagnosis on blood Hg not through
      the indirect pathway of altered fish consumption was a 12% reduction. DD children
      had lower blood Hg concentrations in all analyses. Dental amalgams in children
      with gum-chewing or teeth-grinding habits predicted higher levels. CONCLUSIONS:
      After accounting for dietary and other differences in Hg exposures, total Hg in
      blood was neither elevated nor reduced in CHARGE Study preschoolers with AU/ASD
      compared with unaffected controls, and resembled those of nationally
      representative samples.

PMID- 20056570
TI  - Sources of mercury exposure for U.S. seafood consumers: implications for policy.
AB  - BACKGROUND: Recent policies attempting to reduce adverse effects of methylmercury
      exposure from fish consumption in the United States have targeted reductions in
      anthropogenic emissions from U.S. sources. OBJECTIVES: To analyze the prospects
      for future North American and international emissions controls, we assessed the
      potential contributions of anthropogenic, historical, and natural mercury to
      exposure trajectories in the U.S. population over a 40-year time horizon.
      METHODS: We used models that simulate global atmospheric chemistry (GEOS-Chem);
      the fate, transport, and bioaccumulation of mercury in four types of freshwater
      ecosystems; and mercury cycling among different ocean basins. We considered
      effects on mercury exposures in the U.S. population based on dietary survey
      information and consumption data from the sale of commercial market fish.
      RESULTS: Although North American emissions controls may reduce mercury exposure
      by up to 50% for certain highly exposed groups such as indigenous peoples in the
      Northeast, the potential effects of emissions controls on populations consuming
      marine fish from the commercial market are less certain because of limited
      measurements. CONCLUSIONS: Despite uncertainties in the exposure pathway, results
      indicate that a combination of North American and international emissions
      controls with adaptation strategies is necessary to manage methylmercury risks
      across various demographic groups in the United States.

PMID- 20056571
TI  - Summer heat and mortality in New York City: how hot is too hot?
AB  - BACKGROUND: To assess the public health risk of heat waves and to set criteria
      for alerts for -excessive heat, various meteorologic metrics and models are used
      in different jurisdictions, generally without systematic comparisons of
      alternatives. We report such an analysis for New York City that compared maximum
      heat index with alternative metrics in models to predict daily variation in warm
      season natural-cause mortality from 1997 through 2006. MATERIALS AND METHODS: We
      used Poisson time-series generalized linear models and generalized additive
      models to estimate weather-mortality relationships using various metrics, lag and
      averaging times, and functional forms and compared model fit. RESULTS: A model
      that included cubic functions of maximum heat index on the same and each of the
      previous 3 days provided the best fit, better than models using maximum, minimum,
      or average temperature, or spatial synoptic classification (SSC) of weather type.
      We found that goodness of fit and maximum heat index-mortality functions were
      similar using parametric and nonparametric models. Same-day maximum heat index
      was linearly related to mortality risk across its range. The slopes at lags of 1,
      2, and 3 days were flat across moderate values but increased sharply between
      maximum heat index of 95 degrees F and 100 degrees F (35-38 degrees C). SSC or
      other meteorologic variables added to the maximum heat index model moderately
      improved goodness of fit, with slightly attenuated maximum heat index-mortality
      functions. CONCLUSIONS: In New York City, maximum heat index performed similarly
      to alternative and more complex metrics in estimating mortality risk during hot
      weather. The linear relationship supports issuing heat alerts in New York City
      when the heat index is forecast to exceed approximately 95-100 degrees F.
      Periodic city-specific analyses using recent data are recommended to evaluate
      public health risks from extreme heat.

PMID- 20056572
TI  - Potential for occupational exposure to engineered carbon-based nanomaterials in
      environmental laboratory studies.
AB  - BACKGROUND: The potential exists for laboratory personnel to be exposed to
      engineered carbon-based nanomaterials (CNMs) in studies aimed at producing
      conditions similar to those found in natural surface waters [e.g., presence of
      natural organic matter (NOM)]. OBJECTIVE: The goal of this preliminary
      investigation was to assess the release of CNMs into the laboratory atmosphere
      during handling and sonication into environmentally relevant matrices. METHODS:
      We measured fullerenes (C60), underivatized multiwalled carbon nanotubes (raw
      MWCNT), hydroxylated MWCNT (MWCNT-OH), and carbon black (CB) in air as the
      nanomaterials were weighed, transferred to beakers filled with reconstituted
      freshwater, and sonicated in deionized water and reconstituted freshwater with
      and without NOM. Airborne nanomaterials emitted during processing were quantified
      using two hand-held particle counters that measure total particle number
      concentration per volume of air within the nanometer range (10-1,000 nm) and six
      specific size ranges (300-10,000 nm). Particle size and morphology were
      determined by transmission electron microscopy of air sample filters. DISCUSSION:
      After correcting for background particle number concentrations, it was evident
      that increases in airborne particle number concentrations occurred for each
      nanomaterial except CB during weighing, with airborne particle number
      concentrations inversely related to particle size. Sonicating nanomaterial-spiked
      water resulted in increased airborne nanomaterials, most notably for MWCNT-OH in
      water with NOM and for CB. CONCLUSION: Engineered nanomaterials can become
      airborne when mixed in solution by sonication, especially when nanomaterials are
      functionalized or in water containing NOM. This finding indicates that laboratory
      workers may be at increased risk of exposure to engineered nanomaterials.

PMID- 20056573
TI  - Registration, Evaluation, and Authorization of Chemicals (REACH) is but the first
      step-how far will it take us? Six further steps to improve the European chemicals
      legislation.
AB  - OBJECTIVES: In this commentary we analyze how much data will in fact be generated
      within REACH. CONCLUSIONS: We conclude that the data requirements for many end
      points still have not been determined but depend on prioritization criteria and
      waiving practices that will be decided in the years to come. We propose six
      important steps toward an improved REACH: a) Clarify prioritization and waiving
      criteria. Implement decisions to ensure that sufficient data are obtained to make
      first hazard assessments of as many substances and end points as possible. b)
      Increase data requirements. Introduce data requirements similar to those
      currently required for substances produced or imported in quantities of >or= 10
      metric tons/year for substances produced or imported in quantities of >or= 1
      metric tons/year. c) Develop the tests and approaches needed to satisfy the
      information requirements taking into account resource limitations and the aim to
      reduce animal testing. d) Promote substitution of high risk chemicals. Create an
      effective process for identifying substances of very high concern and for making
      the appropriate risk management decisions for these substances. e) Address the
      control of substances incorporated in articles. And f) acknowledge uncertainties.
      Systematically report lack of data and include this as a basis for risk
      management.

PMID- 20056574
TI  - Individual characteristics associated with PBDE levels in U.S. human milk
      samples.
AB  - BACKGROUND: Reported polybrominated diphenyl ether (PBDE) concentrations in human
      samples in the United States have been higher than in Europe and Asia. Little is
      known about factors that contribute to individual variability in body burden.
      OBJECTIVE: In this large study we measured PBDE concentrations in human milk from
      the United States during 2004-2006. We assessed characteristics associated with
      concentrations in milk and change in milk concentration between 3 and 12 months
      postpartum. METHODS: We analyzed 303 milk samples obtained 3 months postpartum
      for PBDEs. A second sample was analyzed for 83 women still lactating 12 months
      postpartum. PBDE concentrations in milk and variability by individual
      characteristics such as age, parity, and prepregnancy body mass index (BMI) were
      evaluated using generalized linear models. RESULTS: PBDE congeners BDEs 28, 47,
      99, 100, and 153 were detected in > 70% of samples. BDE-47 concentrations were
      the highest, ranging from below the limit of detection to 1,430 ng/g lipid, with
      a median of 28 ng/g lipid. Concentrations of most individual PBDE congeners and
      the sum of BDEs 28, 47, 99, 100, and 153 (SigmaPBDE) were lower among mothers >
      34 years of age compared with those 25-29 years of age and higher among mothers
      with high compared with normal BMI, after adjustment for other covariates. Parity
      was not associated with PBDE concentration. The change in SigmaPBDE concentration
      in milk between 3 and 12 months postpartum was highly variable (median increase,
      14%; interquartile range, -26% to 50%). CONCLUSIONS: PBDEs were detected in
      nearly all human milk samples, varying by maternal weight and age and over the
      course of breast-feeding.

PMID- 20056575
TI  - Integrating omic technologies into aquatic ecological risk assessment and
      environmental monitoring: hurdles, achievements, and future outlook.
AB  - BACKGROUND: In this commentary we present the findings from an international
      consortium on fish toxicogenomics sponsored by the U.K. Natural Environment
      Research Council (Fish Toxicogenomics-Moving into Regulation and Monitoring, held
      21-23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC,
      Canada). OBJECTIVES: The consortium from government agencies, academia, and
      industry addressed three topics: progress in ecotoxicogenomics, regulatory
      perspectives on roadblocks for practical implementation of toxicogenomics into
      risk assessment, and dealing with variability in data sets. DISCUSSION:
      Participants noted that examples of successful application of omic technologies
      have been identified, but critical studies are needed to relate molecular changes
      to ecological adverse outcome. Participants made recommendations for the
      management of technical and biological variation. They also stressed the need for
      enhanced interdisciplinary training and communication as well as considerable
      investment into the generation and curation of appropriate reference omic data.
      CONCLUSIONS: The participants concluded that, although there are hurdles to pass
      on the road to regulatory acceptance, omics technologies are already useful for
      elucidating modes of action of toxicants and can contribute to the risk
      assessment process as part of a weight-of-evidence approach.

PMID- 20056577
TI  - Global gene expression analysis in the livers of rat offspring perinatally
      exposed to low doses of 2,2',4,4'-tetrabromodiphenyl ether.
AB  - BACKGROUND: Polybrominated diphenyl ethers are a group of flame-retardant
      chemicals appearing increasingly in the environment. Their health effects and
      mechanisms of toxicity are poorly understood. OBJECTIVES: We screened for the
      sensitive effects and mechanisms of toxicity of 2,2 ,4,4 -tetra-bromodiphenyl
      ether (BDE-47) by analyzing the gene expression profile in rats exposed to doses
      comparable to human exposure. METHODS: Wistar dams were exposed to vehicle or BDE
      47 (0.002 and 0.2 mg/kg body weight) every fifth day from gestation day 15 to
      postnatal day 20 by injections to caudal vein. Total RNA was extracted from the
      livers of pups and hybridized to the whole-genome RNA expression micro-arrays.
      The list of genes 2-fold differentially expressed was exported to PANTHER and
      Ingenuity Systems for analysis of enriched ontology groups and molecular
      pathways. RESULTS: Oxidoreductase and transferase protein families were enriched
      in exposed rats as were these biological process categories: carbohydrate
      metabolism; electron transport; and lipid, fatty acid, and steroid metabolism.
      Four signaling pathways (cascades of activation of drug-metabolizing enzymes) and
      10 metabolic pathways were significantly enriched. Drug-metabolizing enzymes
      appear to be regulated by BDE-47 through an aryl hydrocarbon receptor-independent
      mechanism. Direct interaction with retinoid X receptor or its upstream cascade
      may be involved. The main metabolic effects consisted of activation of metabolic
      pathways: alpha- and omega-oxidation of fatty acids, glycolysis, and starch
      hydrolysis. CONCLUSIONS: Altered expression of genes involved in metabolic and
      signaling pathways and functions of the organism occurs after perinatal exposure
      of rat offspring to BDE-47 at doses relevant for the general population.

PMID- 20056576
TI  - Mass spectrometric analyses of organophosphate insecticide oxon protein adducts.
AB  - OBJECTIVE: Organophosphate (OP) insecticides continue to be used to control
      insect pests. Acute and chronic exposures to OP insecticides have been documented
      to cause adverse health effects, but few OP-adducted proteins have been
      correlated with these illnesses at the molecular level. Our aim was to review the
      literature covering the current state of the art in mass spectrometry (MS) used
      to identify OP protein biomarkers. DATA SOURCES AND EXTRACTION: We identified
      general and specific research reports related to OP insecticides, OP toxicity, OP
      structure, and protein MS by searching PubMed and Chemical Abstracts for articles
      published before December 2008. DATA SYNTHESIS: A number of OP-based insecticides
      share common structural elements that result in predictable OP-protein adducts.
      The resultant OP-protein adducts show an increase in molecular mass that can be
      identified by MS and correlated with the OP agent. Customized OP-containing
      probes have also been used to tag and identify protein targets that can be
      identified by MS. CONCLUSIONS: MS is a useful and emerging tool for the
      identification of proteins that are modified by activated organophosphate
      insecticides. MS can characterize the structure of the OP adduct and also the
      specific amino acid residue that forms the key bond with the OP. Each protein
      that is modified in a unique way by an OP represents a unique molecular biomarker
      that with further research can lead to new correlations with exposure.

PMID- 20056578
TI  - Arsenic exposure transforms human epithelial stem/progenitor cells into a cancer
      stem-like phenotype.
AB  - BACKGROUND: Inorganic arsenic is a ubiquitous environmental carcinogen affecting
      millions of people worldwide. Evolving theory predicts that normal stem cells
      (NSCs) are transformed into cancer stem cells (CSCs) that then drive oncogenesis.
      In humans, arsenic is carcinogenic in the urogenital system (UGS), including the
      bladder and potentially the prostate, whereas in mice arsenic induces multi-organ
      UGS cancers, indicating that UGS NSCs may represent targets for carcino-genic
      initiation. However, proof of emergence of CSCs induced by arsenic in a stem cell
      population is not available. METHODS: We continuously exposed the human prostate
      epithelial stem/progenitor cell line WPE-stem to an environmentally relevant
      level of arsenic (5 microM) in vitro and determined the acquired cancer
      phenotype. RESULTS: WPE-stem cells rapidly acquired a malignant CSC-like
      phenotype by 18 weeks of exposure, becoming highly invasive, losing contact
      inhibition, and hyper-secreting matrix metalloproteinase-9. When hetero
      transplanted, these cells (designated As-CSC) formed highly pleomorphic,
      aggressive tumors with immature epithelial- and mesenchymal-like cells,
      suggesting a highly pluripotent cell of origin. Consistent with tumor-derived
      CSCs, As-CSCs formed abundant free-floating spheres enriched in CSC-like cells,
      as confirmed by molecular analysis and the fact that only these floating cells
      formed xeno-graft tumors. An early loss of NSC self-renewal gene expression (p63,
      ABCG2, BMI-1, SHH, OCT-4, NOTCH-1) during arsenite exposure was sub-sequently
      reversed as the tumor suppressor gene PTEN was progressively suppressed and the
      CSC-like phenotype acquired. CONCLUSIONS: Arsenite transforms prostate epithelial
      stem/progenitor cells into CSC-like cells, indicating that it can produce CSCs
      from a model NSC population.

PMID- 20056579
TI  - Modulation of cytokine expression in human myeloid dendritic cells by
      environmental endocrine-disrupting chemicals involves epigenetic regulation.
AB  - BACKGROUND: Exposure to environmental endocrine-disrupting chemicals (EDCs) is
      often associated with dysregulated immune homeostasis, but the mechanisms of
      action remain unclear. OBJECTIVES: The aim of this study was to test a hypothesis
      that EDCs regulate the functions of human dendritic cells, a front-line,
      immunoregulatory cell type in contact with the environment. METHODS: We
      investigated circulating myeloid dendritic cells (mDCs) from five subjects and
      measured their responses, with or without coculture with autologous T cells, to
      two common EDCs, nonylphenol (NP) and 4-octylphenol (4-OP). EDC-associated
      cytokine responses, signaling events, and histone modifications were examined
      using ELISA, Western blotting, and chromatin immunoprecipitation (ChIP) assays,
      respectively. RESULTS: In all cases, mDCs treated with NP or 4-OP demonstrated
      increased expression of tumor necrosis factor-alpha (TNF-alpha) but decreased
      baseline and lipopolysaccharide (LPS)-induced (interleukin) (IL)-10 production;
      the increase in TNF-alpha was partially reversible by an estrogen receptor (ER)
      antagonist. Activation of the MKK3/6-p38 signaling pathway marked the effect of
      NP on TNF-alpha expression, concomitant with enhanced levels of methyltranferase
      complex [mixed-lineage leukemia (MLL) and tryptophan-aspartic acid repeat domain
      5 (WDR5)] in the nucleus and of trimethylated H3K4, acetylated H3, and H4 at the
      TNFA gene locus. Further, up-regulated TNF-alpha expression was significantly
      suppressed in NP-treated mDCs by a histone acetyltransferase inhibitor. In the
      presence of NP-treated mDCs, T cells showed increased levels of IL-13 but
      decreased expression of interferon-gamma. CONCLUSIONS: These results suggest that
      NP and 4-OP may have functional effects on the response of mDCs via, in part, the
      ER, MKK3/6-p38 MAPK signaling pathway, and histone modifications, with subsequent
      influence on the T-cell cytokine responses.

PMID- 20056580
TI  - Malondialdehyde-deoxyguanosine adducts among workers of a Thai industrial estate
      and nearby residents.
AB  - BACKGROUND: Humans living near industrial point emissions can experience high
      levels of exposures to air pollutants. Map Ta Phut Industrial Estate in Thailand
      is the location of the largest steel, oil refinery, and petrochemical factory
      complexes in Southeast Asia. Air pollution is an important source of oxidative
      stress and reactive oxygen species, which interact with DNA and lipids, leading
      to oxidative damage and lipid peroxidation, respectively. OBJECTIVE: We measured
      the levels of malondialdehyde-deoxyguanosine (dG) adducts, a biomarker of
      oxidative stress and lipid peroxidation, in petrochemical workers, nearby
      residents, and subjects living in a control district without proximity to
      industrial sources. DESIGN: We conducted a cross-sectional study to compare the
      prevalence of malondialdehyde-dG adducts in groups of subjects experiencing
      various degrees of air pollution. RESULTS: The multivariate regression analysis
      shows that the adduct levels were associated with occupational and environmental
      exposures to air pollution. The highest adduct level was observed in the steel
      factory workers. In addition, the formation of DNA damage tended to be associated
      with tobacco smoking, but without reaching statistical significance. A
      nonsignificant increase in DNA adducts was observed after 4-6 years of employment
      among the petrochemical complexes. CONCLUSIONS: Air pollution emitted from the
      Map Ta Phut Industrial Estate complexes was associated with increased adduct
      levels in petrochemical workers and nearby residents. Considering the mutagenic
      potential of DNA lesions in the carcinogenic process, we recommend measures aimed
      at reducing the levels of air pollution.

PMID- 20056581
TI  - Coumaphos exposure and incident cancer among male participants in the
      Agricultural Health Study (AHS).
AB  - BACKGROUND: Coumaphos is an organophosphate livestock insecticide. Previous
      research in the Agricultural Health Study (AHS) cohort observed a positive
      association between coumaphos and prostate cancer in men with a family history of
      prostate cancer. OBJECTIVES: This study was performed to determine the
      association between coumaphos and other major cancer sites and to explore the
      consistency of the association with prostate cancer early (1993-1999) and later
      (2000-2005) in AHS follow-up. METHODS: This study included 47,822 male licensed
      pesticide applicators. Incident cases were ascertained by linkage to state cancer
      registries, and exposure data were collected by enrollment questionnaire. Poisson
      regression was used to estimate rate ratio (RR) and 95% confidence interval (CI)
      of cancer for coumaphos exposure controlling for potentially confounding
      variables. RESULTS: Approximately 8% of applicators reported use of coumaphos;
      8.5% reported a family history of prostate cancer. Cumulative exposure to
      coumaphos was not associated with cancer risk overall or with any major cancer
      site including prostate. In men with a family history of prostate cancer, we
      observed a positive association between ever use of coumaphos and prostate cancer
      in both early (RR = 2.07; 95% CI, 1.19-3.62, p-interaction = 0.005) and later (RR
      = 1.46; 95% CI, 0.89-2.40; p-interaction = 0.11) periods of follow-up. Across all
      years, this association was statistically significant (RR = 1.65; 95% CI, 1.13
      2.38; p-interaction = 0.004). CONCLUSION: Coumaphos was not associated with any
      cancer evaluated here. In men with a family history of disease, there was
      evidence of an association between coumaphos and prostate cancer, possibly due to
      genetic susceptibility; however, other explanations, including chance, are
      plausible.

PMID- 20056582
TI  - Prenatal and postnatal tobacco exposure and behavioral problems in 10-year-old
      children: results from the GINI-plus prospective birth cohort study.
AB  - BACKGROUND: Prenatal and postnatal tobacco exposure have been reported to be
      associated with behavioral problems. However, the magnitude of the association
      with tobacco exposure at specific periods of exposure is unclear. OBJECTIVE: We
      assessed the relative risk of behavioral problems in children who had been
      exposed to tobacco smoke in utero and postnatally. METHODS: We analyzed data from
      a prospective birth cohort study in two cities in Germany: the German Infant
      Nutrition Intervention. Our sample included 5,991 children born between 1995 and
      1998 as well as their parents. We measured behavioral problems using the Strength
      and Difficulties Questionnaire (SDQ) at follow-up 10 years after birth. According
      to prespecified SDQ cutoff values, children were classified as "normal,"
      "borderline," or "abnormal" according to the subscales "emotional symptoms,"
      "conduct problems," "hyperactivity/inattention," "peer-relationship problems,"
      and a total difficulties score. Smoke exposure and further covariates were
      assessed using parent questionnaires. RESULTS: Compared with children not exposed
      to tobacco smoke, children exposed both pre- and postnatally to tobacco smoke had
      twice the estimated risk [95% confidence interval (CI), 1.4-3.1] of being
      classified as abnormal according to the total difficulties score of the SDQ at 10
      years of age. Children who were only prenatally exposed had a 90% higher relative
      risk (95% CI, 0.9-4.0), whereas children who were only postnatally exposed had a
      30% higher relative risk (95% CI, 0.9-1.9). These results could not be explained
      by confounding by parental education, father's employment, child's time spent in
      front of computer or television screen, being a single father or mother, or
      mother's age. CONCLUSIONS: Prenatal exposure to tobacco smoke is associated with
      behavioral problems in school-age children. Although our findings do not preclude
      the influence of postnatal exposure, prenatal exposure seems to be more
      important.

PMID- 20056583
TI  - Basis of the Massachusetts reference dose and drinking water standard for
      perchlorate.
AB  - OBJECTIVE: Perchlorate inhibits the uptake of iodide in the thyroid. Iodide is
      required to synthesize hormones critical to fetal and neonatal development. Many
      water supplies and foods are contaminated with perchlorate. Exposure standards
      are needed but controversial. Here we summarize the basis of the Massachusetts
      (MA) perchlorate reference dose (RfD) and drinking water standard (DWS), which
      are considerably lower and more health protective than related values derived by
      several other agencies. We also review information regarding perchlorate risk
      assessment and policy. DATA SOURCES: MA Department of Environmental Protection
      (DEP) scientists, with input from a science advisory committee, assessed a wide
      range of perchlorate risk and exposure information. Health outcomes associated
      with iodine insufficiency were considered, as were data on perchlorate in
      drinking water disinfectants. DATA SYNTHESIS: We used a weight-of-the-evidence
      approach to evaluate perchlorate risks, paying particular attention to sensitive
      life stages. A health protective RfD (0.07 microg/kg/day) was derived using an
      uncertainty factor approach with perchlorate-induced iodide uptake inhibition as
      the point of departure. The MA DWS (2 microg/L) was based on risk management
      decisions weighing information on perchlorate health risks and its presence in
      certain disinfectant solutions used to treat drinking water for pathogens.
      CONCLUSIONS: Current data indicate that perchlorate exposures attributable to
      drinking water in individuals at sensitive life stages should be minimized and
      support the MA DEP perchlorate RfD and DWS. Widespread exposure to perchlorate
      and other thyroid toxicants in drinking water and foods suggests that more
      comprehensive policies to reduce overall exposures and enhance iodine nutrition
      are needed.

PMID- 20056584
TI  - Baseline repeated measures from controlled human exposure studies: associations
      between ambient air pollution exposure and the systemic inflammatory biomarkers
      IL-6 and fibrinogen.
AB  - INTRODUCTION: Systemic inflammation may be one of the mechanisms mediating the
      association between ambient air pollution and cardiovascular morbidity and
      mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic
      inflammation that are independent risk factors for cardio-vascular disease.
      OBJECTIVE: We investigated the association between ambient air pollution and
      systemic inflammation using baseline measurements of IL-6 and fibrinogen from
      controlled human exposure studies. METHODS: In this retrospective analysis we
      used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving
      averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and
      particulate matter <or= 2.5 microm in aerodynamic diameter (PM2.5). Linear mixed
      model regression determined the effects of the pollutants on systemic IL-6 and
      fibrinogen. Effect modification by season was considered. RESULTS: We observed a
      positive association between IL-6 and O3 [0.31 SD per O3 interquartile range
      (IQR); 95% confidence interval (CI), 0.080.54] and between IL-6 and SO2 (0.25 SD
      per SO2 IQR; 95% CI, 0.060.43). We observed the strongest effects using 4-day
      moving averages. Responses to pollutants varied by season and tended to be higher
      in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with
      pollution. CONCLUSIONS: This study demonstrates a significant association between
      ambient pollutant levels and baseline levels of systemic IL-6. These findings
      have potential implications for controlled human exposure studies. Future
      research should consider whether ambient pollution exposure before chamber
      exposure modifies IL-6 response.

PMID- 20056585
TI  - Residential pesticides and childhood leukemia: a systematic review and meta
      analysis.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis of previous
      observational epidemiologic studies examining the relationship between
      residential pesticide exposures during critical exposure time windows
      (preconception, pregnancy, and childhood) and childhood leukemia. DATA SOURCES:
      Searches of MEDLINE and other electronic databases were performed (1950-2009).
      Reports were included if they were original epidemiologic studies of childhood
      leukemia, followed a case-control or cohort design, and assessed at least one
      index of residential/household pesticide exposure/use. No language criteria were
      applied. DATA EXTRACTION: Study selection, data abstraction, and quality
      assessment were performed by two independent reviewers. Random effects models
      were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs).
      DATA SYNTHESIS: Of the 17 identified studies, 15 were included in the meta
      analysis. Exposures during pregnancy to unspecified residential pesticides
      (summary OR = 1.54; 95% CI, 1.13-2.11; I2 = 66%), insecticides (OR = 2.05; 95%
      CI, 1.80-2.32; I2 = 0%), and herbicides (OR = 1.61; 95% CI, 1.20-2.16; I2 = 0%)
      were positively associated with childhood leukemia. Exposures during childhood to
      unspecified residential pesticides (OR = 1.38; 95% CI, 1.12-1.70; I2 = 4%) and
      insecticides (OR = 1.61; 95% CI, 1.33-1.95; I2 = 0%) were also positively
      associated with childhood leukemia, but there was no association with herbicides.
      CONCLUSIONS: Positive associations were observed between childhood leukemia and
      residential pesticide exposures. Further work is needed to confirm previous
      findings based on self-report, to examine potential exposure-response
      relationships, and to assess specific pesticides and toxicologically related
      subgroups of pesticides in more detail.

PMID- 20056586
TI  - Silver impairs neurodevelopment: studies in PC12 cells.
AB  - BACKGROUND: Exposure to silver is increasing because of silver nanoparticles in
      consumer products. OBJECTIVES AND METHODS: Many biological effects of silver
      entail actions of Ag+ (monovalent silver ions), so we used neuronotypic PC12
      cells to evaluate the potential for silver to act as a developmental
      neurotoxicant, using chlorpyrifos (CPF), a pesticide known to evoke developmental
      neurotoxicity, as a positive control for comparison. RESULTS: In undifferentiated
      cells, a 1-hr exposure to 10 microM Ag+ inhibited DNA synthesis more potently
      than did 50 microM CPF; it also impaired protein synthesis but to a lesser extent
      than its effect on DNA synthesis, indicating a preferential effect on cell
      replication. Longer exposures led to oxidative stress, loss of viability, and
      reduced numbers of cells. With the onset of cell differentiation, exposure to 10
      microM Ag+ evoked even greater inhibition of DNA synthesis and more oxidative
      stress, selectively impaired neurite formation without suppressing overall cell
      growth, and preferentially suppressed development into the acetylcholine
      phenotype in favor of the dopamine phenotype. Lowering the exposure to 1 microM
      Ag+ reduced the net effect on undifferentiated cells. However, in differentiating
      cells, the lower concentration produced an entirely different pattern, enhancing
      cell numbers by suppressing ongoing cell death and impairing differentiation in
      parallel for both neurotransmitter phenotypes. CONCLUSIONS: Our results show that
      silver has the potential to evoke developmental neurotoxicity even more potently
      than known neurotoxicants, such as CPF, and that the spectrum of effects is
      likely to be substantially different at lower exposures that do not show signs of
      outright toxicity.

PMID- 20056587
TI  - Associations of serum concentrations of organochlorine pesticides with breast
      cancer and prostate cancer in U.S. adults.
AB  - BACKGROUND: Organochlorine (OC) pesticides are a group of environmental endocrine
      disruptors that may be associated with an increased risk for hormone-related
      cancers including cancers of the breast and prostate. However, epidemiologic
      evidence is limited and inconsistent. OBJECTIVES AND METHODS: We used 1999-2004
      National Health and Nutrition Examination Survey data to examine associations
      between serum concentrations of OC pesticides and prostate and breast cancers.
      RESULTS: After adjustment for other covariates, serum concentrations of beta
      hexachlorocyclohexane (HCH) (p for trend = 0.02), trans-nonachlor (p for trend =
      0.002), and dieldrin (p for trend = 0.04) were significantly associated with the
      risk of prevalent prostate cancer. Adjusted odds ratios for the second and third
      tertiles of detectable values were 1.46 [95% confidence interval (CI), 0.52-4.13]
      and 3.36 (95% CI, 1.24-9.10) for beta-HCH; 5.84 (95% CI, 1.06-32.2) and 14.1 (95%
      CI, 2.55-77.9) for trans-nonachlor; and 1.06 (95% CI, 0.30-3.73) and 2.74 (95%
      CI, 1.01-7.49) for dieldrin compared with concentrations in the lowest tertile or
      below the limit of detection. However, there was no positive association between
      serum concentrations of OC pesticides and breast cancer prevalence. CONCLUSION:
      Although further study is necessary to confirm these findings, these results
      suggest that OC pesticide exposures may have a significant effect on cancer risk.
      Efforts to reduce worldwide OC use are warranted.

PMID- 20056588
TI  - Bootstrap-after-bootstrap model averaging for reducing model uncertainty in model
      selection for air pollution mortality studies.
AB  - BACKGROUND: Concerns have been raised about findings of associations between
      particulate matter (PM) air pollution and mortality that have been based on a
      single "best" model arising from a model selection procedure, because such a
      strategy may ignore model uncertainty inherently involved in searching through a
      set of candidate models to find the best model. Model averaging has been proposed
      as a method of allowing for model uncertainty in this context. OBJECTIVES: To
      propose an extension (double BOOT) to a previously described bootstrap model
      averaging procedure (BOOT) for use in time series studies of the association
      between PM and mortality. We compared double BOOT and BOOT with Bayesian model
      averaging (BMA) and a standard method of model selection [standard Akaike's
      information criterion (AIC)]. METHOD: Actual time series data from the United
      States are used to conduct a simulation study to compare and contrast the
      performance of double BOOT, BOOT, BMA, and standard AIC. RESULTS: Double BOOT
      produced estimates of the effect of PM on mortality that have had smaller root
      mean squared error than did those produced by BOOT, BMA, and standard AIC. This
      performance boost resulted from estimates produced by double BOOT having smaller
      variance than those produced by BOOT and BMA. CONCLUSIONS: Double BOOT is a
      viable alternative to BOOT and BMA for producing estimates of the mortality
      effect of PM.

PMID- 20056589
TI  - The implications of using a physiologically based pharmacokinetic (PBPK) model
      for pesticide risk assessment.
AB  - BACKGROUND: A physiologically based pharmacokinetic (PBPK) model would make it
      possible to simulate the dynamics of chemical absorption, distribution,
      metabolism, and elimination (ADME) from different routes of exposures and, in
      theory, could be used to evaluate associations between exposures and biomarker
      measurements in blood or urine. OBJECTIVE: We used a PBPK model to predict
      urinary excretion of 3,5,6-trichloro-2-pyridinol (TCPY), the specific metabolite
      of chlorpyrifos (CPF), in young children. METHODS: We developed a child-specific
      PBPK model for CPF using PBPK models previously developed for rats and adult
      humans. Data used in the model simulation were collected from 13 children 36
      years of age who participated in a cross-sectional pesticide exposure assessment
      study with repeated environmental and biological sampling. RESULTS: The model
      predicted urinary TCPY excretion estimates were consistent with measured levels
      for 2 children with two 24-hr duplicate food samples that contained 350 and 12
      ng/g of CPF, respectively. However, we found that the majority of model outputs
      underpredicted the measured urinary TCPY excretion. CONCLUSIONS: We concluded
      that the potential measurement errors associated with the aggregate exposure
      measurements will probably limit the applicability of PBPK model estimates for
      interpreting urinary TCPY excretion and absorbed CPF dose from multiple sources
      of exposure. However, recent changes in organophosphorus (OP) use have shifted
      exposures from multipathways to dietary ingestion only. Thus, we concluded that
      the PBPK model is still a valuable tool for converting dietary pesticide
      exposures to absorbed dose estimates when the model input data are accurate
      estimates of dietary pesticide exposures.

PMID- 20056590
TI  - National use of asbestos in relation to economic development.
AB  - BACKGROUND: National disparities in asbestos use will likely lead to an unequal
      burden of asbestos diseases. OBJECTIVES: As economic status may be linked to
      asbestos use, we assessed, globally, the relationship between indicators of
      national economic development and asbestos use. METHODS: For the 135 countries
      that have ever used asbestos, per capita asbestos use (kilograms per capita per
      year) was compared with per capita gross domestic product (GDP) in 1990 Geary
      Khamis dollars (GKD) for the period 1920-2003. Countries were grouped into three
      income levels (high, middle, and low) that were adapted from the 2003 World Bank
      categories. RESULTS: The historical pattern of asbestos use followed the
      environmental Kuznets curve in which use by high-income countries peaked when
      incomes attained 10,000-15,000 GKD and essentially ceased at income levels over
      20,000 GKD. Currently, middle- and low-income countries are increasing their use
      of asbestos, closely following the paths once traced by higher income countries.
      CONCLUSIONS: Developing countries have the opportunity to eliminate asbestos use
      sooner than high-income countries and thus reduce the future burden of asbestos
      diseases.

PMID- 20056591
TI  - Within-neighborhood patterns and sources of particle pollution: mobile monitoring
      and geographic information system analysis in four communities in Accra, Ghana.
AB  - BACKGROUND: Sources of air pollution in developing country cities include
      transportation and industrial pollution, biomass and coal fuel use, and
      resuspended dust from unpaved roads. OBJECTIVES: Our goal was to understand
      within-neighborhood spatial variability of particulate matter (PM) in communities
      of varying socioeconomic status (SES) in Accra, Ghana, and to quantify the
      effects of nearby sources on local PM concentration. METHODS: We conducted 1 week
      of morning and afternoon mobile and stationary air pollution measurements in four
      study neighborhoods. PM with aerodynamic diameters <or= 2.5 microm (PM2.5) and
      <or= 10 microm (PM10) was measured continuously, with matched global positioning
      system coordinates; detailed data on local sources were collected at periodic
      stops. The effects of nearby sources on local PM were estimated using linear
      mixed-effects models. RESULTS: In our measurement campaign, the geometric means
      of PM2.5 and PM10 along the mobile monitoring path were 21 and 49 microg/m3,
      respectively, in the neighborhood with highest SES and 39 and 96 microg/m3,
      respectively, in the neighborhood with lowest SES and highest population density.
      PM2.5 and PM10 were as high as 200 and 400 microg/m3, respectively, in some
      segments of the path. After adjusting for other factors, the factors that had the
      largest effects on local PM pollution were nearby wood and charcoal stoves,
      congested and heavy traffic, loose dirt road surface, and trash burning.
      CONCLUSIONS: Biomass fuels, transportation, and unpaved roads may be important
      determinants of local PM variation in Accra neighborhoods. If confirmed by
      additional or supporting data, the results demonstrate the need for effective and
      equitable interventions and policies that reduce the impacts of traffic and
      biomass pollution.

PMID- 20056592
TI  - Sucrose synthase is an integral component of the cellulose synthesis machinery.
AB  - Cellulose synthesis in plants is believed to be carried out by the plasma
      membrane-associated rosette structure which can be observed by electron
      microscopy. Despite decade-long speculation, it had not been demonstrated whether
      the rosette is the site of catalytic activity of cellulose synthesis. To
      determine the relationship between this structure and cellulose synthesis, we
      successfully isolated detergent-insoluble rosettes from the plasma membrane of
      bean epicotyls. However, the purified rosettes did not possess cellulose
      synthesis activity in vitro. Conversely, detergent-soluble granular particles of
      approximately 9.5-10 nm diameter were also isolated and exhibited UDP-glucose
      binding activity and possessed beta-1,4-glucan (cellulose) synthesis activity in
      vitro. The particle, referred to as the catalytic unit of cellulose synthesis,
      was enriched with a 78 kDa polypeptide which was verified as sucrose synthase
      like by mass spectrometry and immunoblotting. The catalytic units were able to
      bind to the rosettes and retained the cellulose synthesis activity in the
      presence of UDP-glucose or sucrose plus UDP when supplemented with magnesium. The
      incorporation of the catalytic unit into the rosette structure was confirmed by
      immunogold labeling with anti-sucrose synthase antibodies under an electron
      microscope. Our results suggest that the plasma membrane-associated rosette
      anchors the catalytic unit of cellulose synthesis to form the functional
      cellulose synthesis machinery.

PMID- 20056593
TI  - Structured care for patients after acute myocardial infarction: sudden cardiac
      death prevention--data from the Leiden MISSION! AMI study.
AB  - AIMS: To assess the number of patients in daily clinical practice that meets
      criteria for implantation of an implantable cardioverter defibrillator (ICD)
      following acute myocardial infarction (AMI) when treated according to an
      aggressive treatment protocol. METHODS AND RESULTS: Patients were treated
      according to the MISSION! protocol. The protocol encompasses pre-hospital, in
      hospital, and outpatient clinical framework for the acute and chronic treatment
      of AMI patients and the decision making regarding primary prevention of sudden
      cardiac death (SCD). A total of 676 consecutive AMI patients (78% male, mean age
      59 +/- 12 years) treated according to the MISSION! protocol were included in this
      analysis. Left ventricular ejection fraction at 3 months was 54 +/- 10%. Only 39
      (6%) patients met criteria for implantation of an ICD <1 year post-MI. These
      patients suffered more extensive infarctions as indicated by higher peak troponin
      T values (mean 14.5 +/- 8.3 vs. 6.5 +/- 14.7 microg/L; P < 0.001) and had more
      left anterior descending artery related infarctions (79 vs. 46%; P < 0.001).
      Cumulative first appropriate therapy rate was 15% at 3 years follow-up. No SCD
      was observed in the study population. CONCLUSION: Aggressive treatment of AMI
      patients and close monitoring after the index event according to a standardized
      protocol, results in only a small number of patients becoming candidate for
      prophylactic ICD implantation. An easy-to-use protocol combining aggressive
      reperfusion, optimal medication, and a risk stratification algorithm tailored to
      fit within routine practice may help to maintain ICD implantation rates within
      manageable proportions.

PMID- 20056594
TI  - Validation of the AF-QoL, a disease-specific quality of life questionnaire for
      patients with atrial fibrillation.
AB  - AIMS: To assess the performance of AF-QoL, a quality of life questionnaire for
      patients with atrial fibrillation (AF). METHODS AND RESULTS: Observational,
      prospective, multicentre study in 29 Spanish centres. Three patients' groups were
      identified at baseline visit: AF patients receiving a new therapeutic
      intervention according to physician criteria (intervention group); AF clinically
      stable patients according to physician evaluation (clinically stable group); and
      patients in a stable condition for more than 1 year after a myocardial infarction
      (control group). All patients were > or = 18 years. Follow-up visit was at 1
      month (clinically stable group) and 3 +/- 1 months (intervention group).
      Sociodemographic and clinical information was gathered. AF-QoL, SF-36, and
      patient self-perception of general health status were administered. A total of
      417 patients was included. Mean (SD) age was 61.2 (12.4), 31.4% women. AF-QoL
      mean overall score in AF patients (43.6) was lower (worse health-related quality
      of life, HRQoL) than in the control group (51.7) (P < 0.05). At baseline,
      patients with higher frequency of symptoms (P < 0.05) and worse NYHA functional
      class (P < 0.01) reported lower AF-QoL scores. AF-QoL and SF-36 correlated in all
      of their domains (r = 0.14-0.8, P < 0.01). AF-QoL showed good internal
      consistency (0.92) and test-retest reliability (0.86). CONCLUSION: AF-QoL is a
      valid and reliable HRQoL measure. Further investigation is recommended before
      using it in clinical practice.

PMID- 20056595
TI  - Device-based impedance measurement is a useful and accurate tool for direct
      assessment of intrathoracic fluid accumulation in heart failure.
AB  - AIMS: Heart failure patients are often equipped with implanted devices and are
      frequently hospitalized due to volume overload. Reliable prediction of imminent
      fluid congestion has the potential to provide early detection of cardiac
      decompensation and therefore might be capable of enhancing therapy management. We
      investigated whether implant-based impedance (Z) measurement is closely
      correlated with directly assessed extravascular lung water and might thus be
      useful for patient monitoring. METHODS AND RESULTS: In sheep, pulmonary fluid
      congestion was induced. Continuous haemodynamic monitoring was performed and
      extravascular lung water index (EVLWI) assessed. An implanted device with a right
      ventricular lead measured Z using different electrode configurations. All animals
      developed gradual pulmonary fluid accumulation leading to inclining lung oedema:
      EVLWI did increase from 9.5 +/- 1 to 21.1 +/- 5.1 mL/kg (+127%). A concomitant
      decrease of Z by up to 23%, depending on the electrode configuration, was
      observed and regression analysis between Z and EVLWI yielded a significant
      inverse correlation. CONCLUSION: Changes of Z show a strong inverse correlation
      with changes of directly measured EVLWI. This allows the application of Z as a
      measure of intrathoracic fluid status and has the potential to optimize patient
      care, especially in the context of evolving telemedicine concepts.

PMID- 20056596
TI  - Atrial activation time and pattern of linear triple-site vs. single-site atrial
      pacing after cardioversion in patients with atrial fibrillation.
AB  - AIMS: Multisite atrial pacing has been suggested to be effective in suppressing
      atrial fibrillation (AF), however, the effect of linear triple-site atrial pacing
      (LTSP) in humans has not been evaluated. We compared the effects of LTSP to
      single-site atrial pacing (SSP) on the atrial activation and wavefront
      propagation pattern in patients with persistent AF. METHODS AND RESULTS: In 10
      patients with persistent AF, the effects of LTSP and SSP were evaluated by left
      atrial (LA) endocardial non-contact multielectrode array mapping and multipolar
      catheters. LTSP and SSP were delivered from the high right atrium (HRA), the
      distal coronary sinus (CS), and within the LA at the site showing maximal overlay
      of low-voltage zones during sinus rhythm and pacing at HRA and CS. Atrial
      activation time and pattern, P wave duration, and the prevention of AF induced by
      burst pacing were assessed with these pacing interventions. Compared with SSP,
      LTSP at the HRA, CS, and LA shortened atrial activation times (183 +/- 24 vs. 174
      +/- 24 ms, 186 +/- 29 vs. 166 +/- 28 ms, and 171 +/- 40 vs. 163 +/- 39 ms; P <
      0.05, respectively). P wave duration was shorter with LTSP than SSP at all three
      sites (141.7 +/- 35.1 vs. 146.9 +/- 38.5 ms, 138.1 +/- 34.6 vs. 145.7 +/- 33.7
      ms, and 142.7 +/- 33.4 vs. 151.3 +/- 35.1 ms; P < 0.05, respectively). LTSP
      initially depolarized a larger area than SSP, and produced more uniform and
      planar wavefront propagation. LTSP prevented the burst-induction of AF during LA
      pacing in 3 of 10 patients, while SSP was never successful. CONCLUSION: In
      patients with persistent AF, LTSP provided more rapid and uniform activation of
      the atria compared with SSP, which was associated with prevention of burst
      induction of AF in some patients. Further study is required to determine whether
      LTSP can modify the substrate of chronic AF, leading to frank AF suppression.

PMID- 20056597
TI  - Pericardial effusion in atrial fibrillation ablation: a comparison between
      cryoballoon and radiofrequency pulmonary vein isolation.
AB  - AIMS: Atrial fibrillation (AF) ablation is increasingly being performed in
      electrophysiology laboratories. Pericardial effusion (PE) is certainly one of the
      most frequently observed complications during AF ablation. The aim of our study
      was to investigate the incidence and outcome of PE following cryothermal energy
      balloon ablation (CBA) in comparison with conventional circumferential pulmonary
      vein isolation with a focal radiofrequency (RF) catheter. METHODS AND RESULTS: A
      total of 133 consecutive patients (105 males) with paroxysmal AF were included in
      this study. Forty-six patients (36 males) underwent CBA (Arctic Front, Medtronic,
      USA) and 87 (69 males) point-by-point RF ablation guided by electroanatomical
      mapping (Carto, Biosense Webster, Diamond Bar, CA, USA). Ablation was performed
      under general anaesthesia with both techniques. All patients underwent a 2D
      transthoracic echocardiogram within 24 h before and after the procedure as
      routinely performed in our centre. Pericardial effusion was detected in 19
      (14.2%) of 133 patients. Sixteen patients presented mild effusion, one moderate
      effusion, and two pericardial tamponades. There was no significant difference in
      the incidence of PE between the cryoballoon and the RF group (11 vs. 16%). A
      longer procedural time, coronary artery disease, and arterial hypertension were
      found to be independent predictors of PE during AF ablation. CONCLUSION:
      Pericardial effusion occurred in a similar proportion following CBA and RF
      ablation for AF. Pericardial effusion was mostly mild and asymptomatic, with
      benign clinical outcome not requiring additional hospitalization days.

PMID- 20056598
TI  - In situ D-periodic molecular structure of type II collagen.
AB  - Collagens are essential components of extracellular matrices in multicellular
      animals. Fibrillar type II collagen is the most prominent component of articular
      cartilage and other cartilage-like tissues such as notochord. Its in situ
      macromolecular and packing structures have not been fully characterized, but an
      understanding of these attributes may help reveal mechanisms of tissue assembly
      and degradation (as in osteo- and rheumatoid arthritis). In some tissues such as
      lamprey notochord, the collagen fibrillar organization is naturally crystalline
      and may be studied by x-ray diffraction. We used diffraction data from native and
      derivative notochord tissue samples to solve the axial, D-periodic structure of
      type II collagen via multiple isomorphous replacement. The electron density maps
      and heavy atom data revealed the conformation of the nonhelical telopeptides and
      the overall D-periodic structure of collagen type II in native tissues, data that
      were further supported by structure prediction and transmission electron
      microscopy. These results help to explain the observed differences in collagen
      type I and type II fibrillar architecture and indicate the collagen type II cross
      link organization, which is crucial for fibrillogenesis. Transmission electron
      microscopy data show the close relationship between lamprey and mammalian
      collagen fibrils, even though the respective larger scale tissue architecture
      differs.

PMID- 20056599
TI  - Structure of GroEL in complex with an early folding intermediate of alanine
      glyoxylate aminotransferase.
AB  - Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by
      mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have
      previously shown that P11L and I340M polymorphisms together with I244T mutation
      (AGXT-LTM) represent a conformational disease that could be amenable to
      pharmacological intervention. Thus, the study of the folding mechanism of AGXT is
      crucial to understand the molecular basis of the disease. Here, we provide
      biochemical and structural data showing that AGXT-LTM is able to form non-native
      folding intermediates. The three-dimensional structure of a complex between the
      bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been
      solved by cryoelectron microscopy. The electron density map shows the protein
      substrate in a non-native extended conformation that crosses the GroEL central
      cavity. Addition of ATP to the complex induces conformational changes on the
      chaperonin and the internalization of the protein substrate into the folding
      cavity. The structure provides a three-dimensional picture of an in vivo early
      ATP-dependent step of the folding reaction cycle of the chaperonin and supports a
      GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM
      mutant protein through forced unfolding mechanism.

PMID- 20056600
TI  - Non-peptidic thrombospondin-1 mimics as fibroblast growth factor-2 inhibitors: an
      integrated strategy for the development of new antiangiogenic compounds.
AB  - Endogenous inhibitors of angiogenesis, such as thrombospondin-1 (TSP-1), are
      promising sources of therapeutic agents to treat angiogenesis-driven diseases,
      including cancer. TSP-1 regulates angiogenesis through different mechanisms,
      including binding and sequestration of the angiogenic factor fibroblast growth
      factor-2 (FGF-2), through a site located in the calcium binding type III repeats.
      We hypothesized that the FGF-2 binding sequence of TSP-1 might serve as a
      template for the development of inhibitors of angiogenesis. Using a peptide array
      approach followed by binding assays with synthetic peptides and recombinant
      proteins, we identified a FGF-2 binding sequence of TSP-1 in the 15-mer sequence
      DDDDDNDKIPDDRDN. Molecular dynamics simulations, taking the full flexibility of
      the ligand and receptor into account, and nuclear magnetic resonance identified
      the relevant residues and conformational determinants for the peptide-FGF
      interaction. This information was translated into a pharmacophore model used to
      screen the NCI2003 small molecule databases, leading to the identification of
      three small molecules that bound FGF-2 with affinity in the submicromolar range.
      The lead compounds inhibited FGF-2-induced endothelial cell proliferation in
      vitro and affected angiogenesis induced by FGF-2 in the chicken chorioallantoic
      membrane assay. These small molecules, therefore, represent promising leads for
      the development of antiangiogenic agents. Altogether, this study demonstrates
      that new biological insights obtained by integrated multidisciplinary approaches
      can be used to develop small molecule mimics of endogenous proteins as
      therapeutic agents.

PMID- 20056601
TI  - N-terminal extension of the cholera toxin A1-chain causes rapid degradation after
      retrotranslocation from endoplasmic reticulum to cytosol.
AB  - Cholera toxin travels from the plasma membrane to the endoplasmic reticulum of
      host cells, where a portion of the toxin, the A1-chain, is unfolded and targeted
      to a protein-conducting channel for retrotranslocation to the cytosol. Unlike
      most retrotranslocation substrates, the A1-chain escapes degradation by the
      proteasome and refolds in the cytosol to induce disease. How this occurs remains
      poorly understood. Here, we show that an unstructured peptide appended to the N
      terminus of the A1-chain renders the toxin functionally inactive. Cleavage of the
      peptide extension prior to cell entry rescues toxin half-life and function. The
      loss of toxicity is explained by rapid degradation by the proteasome after
      retrotranslocation to the cytosol. Degradation of the mutant toxin does not
      follow the N-end rule but depends on the two Lys residues at positions 4 and 17
      of the native A1-chain, consistent with polyubiquitination at these sites. Thus,
      retrotranslocation and refolding of the wild-type A1-chain must proceed in a way
      that protects these Lys residues from attack by E3 ligases.

PMID- 20056602
TI  - Pulmonary collectins protect macrophages against pore-forming activity of
      Legionella pneumophila and suppress its intracellular growth.
AB  - Pulmonary collectins, surfactant proteins A (SP-A) and D (SP-D), play important
      roles in innate immunity of the lung. Legionella pneumophila is a bacterial
      respiratory pathogen that can replicate within macrophages and causes
      opportunistic infections. L. pneumophila possesses cytolytic activity, resulting
      from insertion of pores in the macrophage membrane upon contact. We examined
      whether pulmonary collectins play protective roles against L. pneumophila
      infection. SP-A and SP-D bound to L. pneumophila and its lipopolysaccharide (LPS)
      and inhibited the bacterial growth in a Ca(2+)-dependent manner. The addition of
      LPS in the culture blocked the inhibitory effects on L. pneumophila growth by the
      collectins, indicating the importance of LPS-collectin interaction. When
      differentiated THP-1 cells were infected with L. pneumophila in the presence of
      SP-A and SP-D, the number of permeable cells was significantly decreased,
      indicating that pulmonary collectins inhibit pore-forming activity of L.
      pneumophila. The number of live bacteria within the macrophages on days 1-4 after
      infection was significantly decreased when infection was performed in the
      presence of pulmonary collectins. The phagocytosis experiments with the pH
      sensitive dye-labeled bacteria revealed that pulmonary collectins promoted
      bacterial localization to an acidic compartment. In addition, SP-A and SP-D
      significantly increased the number of L. pneumophila co-localized with LAMP-1.
      These results indicate that pulmonary collectins protect macrophages against
      contact-dependent cytolytic activity of L. pneumophila and suppress intracellular
      growth of the phagocytosed bacteria. The promotion of lysosomal fusion with
      Legionella-containing phagosomes constitutes a likely mechanism of L. pneumophila
      growth suppression by the collectins.

PMID- 20056603
TI  - Elevated expression of Paneth cell CRS4C in ileitis-prone SAMP1/YitFc mice:
      regional distribution, subcellular localization, and mechanism of action.
AB  - Paneth cells at the base of small intestinal crypts of Lieberkuhn secrete host
      defense peptides and proteins, including alpha-defensins, as mediators of innate
      immunity. Mouse Paneth cells also express alpha-defensin-related Defcr-rs genes
      that code for cysteine-rich sequence 4C (CRS4C) peptides that have a unique CPX
      triplet repeat motif. In ileitis-prone SAMP1/YitFc mice, Paneth cell levels of
      CRS4C mRNAs and peptides are induced more than a 1000-fold relative to non-prone
      strains as early as 4 weeks of age, with the mRNA and peptide levels highest in
      distal ileum and below detection in duodenum. CRS4C-1 peptides are found
      exclusively in Paneth cells where they occur only in dense core granules and thus
      are secreted to function in the intestinal lumen. CRS4C bactericidal peptide
      activity is membrane-disruptive in that it permeabilizes Escherichia coli and
      induces rapid microbial cell K(+) efflux, but in a manner different from mouse
      alpha-defensin cryptdin-4. In in vitro studies, inactive pro-CRS4C-1 is converted
      to bactericidal CRS4C-1 peptide by matrix metalloproteinase-7 (MMP-7) proteolysis
      of the precursor proregion at the same residue positions that MMP-7 activates
      mouse pro-alpha-defensins. The absence of processed CRS4C in protein extracts of
      MMP-7-null mouse ileum demonstrates the in vivo requirement for intracellular MMP
      7 in pro-CRS4C processing.

PMID- 20056604
TI  - Expression and function of epithelial anoctamins.
AB  - The calcium-activated chloride channel anoctamin1 (ANO1; TMEM16A) is fundamental
      for the function of epithelial organs. Mice lacking ANO1 expression exhibit
      transport defects and a pathology similar to cystic fibrosis. They also show a
      general defect of epithelial electrolyte transport. Here we analyzed expression
      of all ten members (ANO1-ANO10) in a broad range of murine tissues and detected
      predominant expression of ANO1, 6, 7, 8, 9, 10 in epithelial tissues, while ANO2,
      3, 4, 5 are common in neuronal and muscle tissues. When expressed in Fisher Rat
      Thyroid (FTR) cells, all ANO proteins localized to the plasma membrane but only
      ANO1, 2, 6, and 7 produced Ca(2+)-activated Cl(-) conductance, as analyzed by ATP
      induced iodide quenching of YFP fluorescence. In contrast ANO9 and ANO10
      suppressed baseline Cl(-) conductance and coexpression of ANO9 with ANO1
      inhibited ANO1 activity. Patch clamping of ANO-expressing FRT cells indicated
      that apart from ANO1 also ANO6 and 10 produced chloride currents, albeit with
      very different Ca(2+) sensitivity and activation time. We conclude that each
      tissue expresses a set of anoctamins that form cell- and tissue-specific Ca(2+)
      dependent Cl(-) channels.

PMID- 20056605
TI  - P2X4 activation modulates volume-sensitive outwardly rectifying chloride channels
      in rat hepatoma cells.
AB  - Volume-sensitive outwardly rectifying (VSOR) Cl(-) channels are critical for the
      regulatory volume decrease (RVD) response triggered upon cell swelling. Recent
      evidence indicates that H(2)O(2) plays an essential role in the activation of
      these channels and that H(2)O(2) per se activates the channels under isotonic
      isovolumic conditions. However, a significant difference in the time course for
      current onset between H(2)O(2)-induced and hypotonicity-mediated VSOR Cl(-)
      activation is observed. In several cell types, cell swelling induced by hypotonic
      challenges triggers the release of ATP to the extracellular medium, which in
      turn, activates purinergic receptors and modulates cell volume regulation. In
      this study, we have addressed the effect of purinergic receptor activation on
      H(2)O(2)-induced and hypotonicity-mediated VSOR Cl(-) current activation. Here we
      show that rat hepatoma cells (HTC) exposed to a 33% hypotonic solution responded
      by rapidly activating VSOR Cl(-) current and releasing ATP to the extracellular
      medium. In contrast, cells exposed to 200 microm H(2)O(2) VSOR Cl(-) current
      onset was significantly slower, and ATP release was not detected. In cells
      exposed to either 11% hypotonicity or 200 microm H(2)O(2), exogenous addition of
      ATP in the presence of extracellular Ca(2+) resulted in a decrease in the half
      time for VSOR Cl(-) current onset. Conversely, in cells that overexpress a
      dominant-negative mutant of the ionotropic receptor P2X4 challenged with a 33%
      hypotonic solution, the half-time for VSOR Cl(-) current onset was significantly
      slowed down. Our results indicate that, at high hypotonic imbalances, swelling
      induced ATP release activates the purinergic receptor P2X4, which in turn
      modulates the time course of VSOR Cl(-) current onset in a extracellular Ca(2+)
      dependent manner.

PMID- 20056606
TI  - Apical surface expression of aspartic protease Plasmepsin 4, a potential
      transmission-blocking target of the plasmodium ookinete.
AB  - To invade its definitive host, the mosquito, the malaria parasite must cross the
      midgut peritrophic matrix that is composed of chitin cross-linked by chitin
      binding proteins and then develop into an oocyst on the midgut basal lamina.
      Previous evidence indicates that Plasmodium ookinete-secreted chitinase is
      important in midgut invasion. The mechanistic role of other ookinete-secreted
      enzymes in midgut invasion has not been previously examined. De novo mass
      spectrometry sequencing of a protein obtained by benzamidine affinity column of
      Plasmodium gallinaceum ookinete axenic culture supernatant demonstrated the
      presence of an ookinete-secreted plasmepsin, an aspartic protease previously only
      known to be present in the digestive vacuole of asexual stage malaria parasites.
      This plasmepsin, the ortholog of Plasmodium falciparum plasmepsin 4, was
      designated PgPM4. PgPM4 and PgCHT2 (the P. gallinaceum ortholog of P. falciparum
      chitinase PfCHT1) are both localized on the ookinete apical surface, and both are
      present in micronemes. Aspartic protease inhibitors (peptidomimetic and natural
      product), calpain inhibitors, and anti-PgPM4 monoclonal antibodies significantly
      reduced parasite infectivity for mosquitoes. These results suggest that
      plasmepsin 4, previously known only to function in the digestive vacuole of
      asexual blood stage Plasmodium, plays a role in how the ookinete interacts with
      the mosquito midgut interactions as it becomes an oocyst. These data are the
      first to delineate a role for an aspartic protease in mediating Plasmodium
      invasion of the mosquito and demonstrate the potential for plasmepsin 4 as a
      malaria transmission-blocking vaccine target.

PMID- 20056607
TI  - First crystal structure of L-lysine 6-dehydrogenase as an NAD-dependent amine
      dehydrogenase.
AB  - A gene encoding an L-lysine dehydrogenase was identified in the hyperthermophilic
      archaeon Pyrococcus horikoshii. The gene was overexpressed in Escherichia coli,
      and its product was purified and characterized. The expressed enzyme is the most
      thermostable L-lysine dehydrogenase yet described, with a half-life of 180 min at
      100 degrees C. The product of the enzyme's catalytic activity is Delta(1)
      piperideine-6-carboxylate, which makes this enzyme an L-lysine 6-dehydrogenase
      (EC 1.4.1.18) that catalyzes the reductive deamination of the epsilon- amino
      group and a type of NAD-dependent amine dehydrogenase. The three-dimensional
      structure of the enzyme was determined using the mercury-based multiple
      wavelength anomalous dispersion method at a resolution of 2.44 A in the presence
      of NAD and sulfate ion. The asymmetric unit consisted of two subunits, and a
      crystallographic 2-fold axis generated the functional dimer. Each monomer
      consisted of a Rossmann fold domain and a C-terminal catalytic domain, and the
      fold of the catalytic domain showed similarity to that of saccharopine reductase.
      Notably, the structures of subunits A and B differed significantly. In subunit A,
      the active site contained a sulfate ion that was not seen in subunit B.
      Consequently, subunit A adopted a closed conformation, whereas subunit B adopted
      an open one. In each subunit, one NAD molecule was bound to the active site in an
      anti-conformation, indicating that the enzyme makes use of pro-R-specific hydride
      transfer between the two hydrides at C-4 of NADH (type A specificity). This is
      the first description of the three-dimensional structure of l-lysine 6
      dehydrogenase as an NAD-dependent amine dehydrogenase.

PMID- 20056608
TI  - Arabidopsis uracil DNA glycosylase (UNG) is required for base excision repair of
      uracil and increases plant sensitivity to 5-fluorouracil.
AB  - Uracil in DNA arises by misincorporation of dUMP during replication and by
      hydrolytic deamination of cytosine. This common lesion is actively removed
      through a base excision repair (BER) pathway initiated by a uracil DNA
      glycosylase (UDG) activity that excises the damage as a free base. UDGs are
      classified into different families differentially distributed across eubacteria,
      archaea, yeast, and animals, but remain to be unambiguously identified in plants.
      We report here the molecular characterization of AtUNG (Arabidopsis thaliana
      uracil DNA glycosylase), a plant member of the Family-1 of UDGs typified by
      Escherichia coli Ung. AtUNG exhibits the narrow substrate specificity and single
      stranded DNA preference that are characteristic of Ung homologues. Cell extracts
      from atung(-/-) mutants are devoid of UDG activity, and lack the capacity to
      initiate BER on uracil residues. AtUNG-deficient plants do not display any
      apparent phenotype, but show increased resistance to 5-fluorouracil (5-FU), a
      cytostatic drug that favors dUMP misincorporation into DNA. The resistance of
      atung(-/-) mutants to 5-FU is accompanied by the accumulation of uracil residues
      in DNA. These results suggest that AtUNG excises uracil in vivo but generates
      toxic AP sites when processing abundant U:A pairs in dTTP-depleted cells.
      Altogether, our findings point to AtUNG as the major UDG activity in Arabidopsis.

PMID- 20056610
TI  - Down-regulation of tissue inhibitor of metalloproteinase-3 (TIMP-3) expression is
      necessary for adipocyte differentiation.
AB  - Matrix metalloproteinase activity is essential for proper extracellular matrix
      remodeling that takes place during adipose tissue formation. Four tissue
      inhibitors of matrix metalloproteinases (TIMPs) regulate their activity. However,
      the role of TIMPs in adipocyte differentiation is poorly understood. We found
      that the expression of all TIMPs was modified during adipocyte differentiation,
      but that of TIMP-3 was distinguished by its extreme down-regulation. TIMP-3
      expression was closely linked to the differentiation process. Indeed, it remained
      low during the adipocyte differentiation but increased when cell differentiation
      was prevented. We identified the transcription factor Sp1 as being responsible
      for the regulation of TIMP-3 expression during adipocyte differentiation.
      Overexpression of TIMP-3 reduced adipocyte differentiation, underlining its
      active role in this process. TIMP-3 overexpression decreased the expression of
      the early and obligate key inductors of adipogenesis Kruppel-like factor 4
      (Klf4), early growth response 2 (Egr2/Krox20), and CAAT/enhancer-binding protein
      beta (C/EBPbeta). Our results indicate that during preadipocyte differentiation,
      the Sp1-dependent decrease in TIMP-3 expression is required for the successful
      implementation of the adipocyte differentiation program.

PMID- 20056609
TI  - Non-visual arrestins are constitutively associated with the centrosome and
      regulate centrosome function.
AB  - In addition to regulating receptor activity, non-visual arrestins function as
      scaffolds for numerous intracellular signaling cascades and as regulators of gene
      transcription. Here we report that the two non-visual arrestins, arrestin2 and
      arrestin3, localize to the centrosome, a key organelle involved in microtubule
      nucleation and bipolar mitotic spindle assembly. Both arrestins co-localized with
      the centrosomal marker gamma-tubulin during interphase and mitosis and were found
      in purified centrosome preparations. In vitro binding assays demonstrated that
      both arrestins directly interact with gamma-tubulin. Knockdown of either arrestin
      by RNA interference resulted in multinucleation, centrosome amplification, and
      mitotic defects, although only the loss of arrestin2 triggered aberrant
      microtubule nucleation. Importantly, overexpression of wild type arrestin rescued
      the multinucleation phenotype and restored normal centrosome number in arrestin
      siRNA-transfected cells. Moreover, overexpression of arrestin2 or -3 rescued the
      multinucleation defect observed in MDA-MB-231 breast cancer cells. Taken
      together, our data reveal that non-visual arrestins are novel centrosomal
      components and regulate normal centrosome function.

PMID- 20056611
TI  - Transient and big are key features of an invertebrate T-type channel (LCav3) from
      the central nervous system of Lymnaea stagnalis.
AB  - Here we describe features of the first non-mammalian T-type calcium channel
      (LCa(v)3) expressed in vitro. This molluscan channel possesses combined
      biophysical properties that are reminiscent of all mammalian T-type channels. It
      exhibits T-type features such as "transient" kinetics, but the "tiny" label,
      usually associated with Ba(2+) conductance, is hard to reconcile with the
      "bigness" of this channel in many respects. LCa(v)3 is 25% larger than any
      voltage-gated ion channel expressed to date. It codes for a massive, 322-kDa
      protein that conducts large macroscopic currents in vitro. LCa(v)3 is also the
      most abundant Ca(2+) channel transcript in the snail nervous system. A window
      current at typical resting potentials appears to be at least as large as that
      reported for mammalian channels. This distant gene provides a unique perspective
      to analyze the structural, functional, drug binding, and evolutionary aspects of
      T-type channels.

PMID- 20056612
TI  - Quantitative proteomics analysis of cell cycle-regulated Golgi disassembly and
      reassembly.
AB  - During mitosis, the stacked structure of the Golgi undergoes a continuous
      fragmentation process. The generated mitotic fragments are evenly distributed
      into the daughter cells and reassembled into new Golgi stacks. This disassembly
      and reassembly process is critical for Golgi biogenesis during cell division, but
      the underlying molecular mechanism is poorly understood. In this study, we have
      recapitulated this process using an in vitro assay and analyzed the proteins
      associated with interphase and mitotic Golgi membranes using a proteomic
      approach. Incubation of purified rat liver Golgi membranes with mitotic HeLa cell
      cytosol led to fragmentation of the membranes; subsequent treatment of these
      membranes with interphase cytosol allowed the reassembly of the Golgi fragments
      into new Golgi stacks. These membranes were then used for quantitative proteomics
      analyses by combining the isobaric tags for relative and absolute quantification
      approach with OFFGEL isoelectric focusing separation and liquid chromatography
      matrix assisted laser desorption ionization-tandem mass spectrometry. In three
      independent experiments, a total of 1,193 Golgi-associated proteins were
      identified and quantified. These included broad functional categories, such as
      Golgi structural proteins, Golgi resident enzymes, SNAREs, Rab GTPases, cargo,
      and cytoskeletal proteins. More importantly, the combination of the quantitative
      approach with Western blotting allowed us to unveil 84 proteins with significant
      changes in abundance under the mitotic condition compared with the interphase
      condition. Among these proteins, several COPI coatomer subunits (alpha, beta,
      gamma, and delta) are of particular interest. Altogether, this systematic
      quantitative proteomic study revealed candidate proteins of the molecular
      machinery that control the Golgi disassembly and reassembly processes in the cell
      cycle.

PMID- 20056613
TI  - Defects in 18 S or 28 S rRNA processing activate the p53 pathway.
AB  - The p53 tumor suppressor pathway is activated by defective ribosome synthesis.
      Ribosomal proteins are released from the nucleolus and block human double minute
      2 (Hdm2) that targets p53 for degradation. However, it remained elusive how
      abrogation of individual rRNA processing pathways contributes to p53
      stabilization. Here, we show that selective inhibition of 18 S rRNA processing
      provokes accumulation of p53 as efficiently as abrogated 28 S rRNA maturation. We
      describe hUTP18 as a novel mammalian rRNA processing factor that is specifically
      involved in 18 S rRNA production. hUTP18 was essential for the cleavage of the 5'
      external transcribed spacer leader sequence from the primary polymerase I
      transcript, but was dispensable for rRNA transcription. Because maturation of the
      28 S rRNA was unaffected in hUTP18-depleted cells, our results suggest that the
      integrity of both the 18 S and 28 S rRNA synthesis pathways can be monitored
      independently by the p53 pathway. Interestingly, accumulation of p53 after hUTP18
      knock down required the ribosomal protein L11. Therefore, cells survey the
      maturation of the small and large ribosomal subunits by separate molecular
      routes, which may merge in an L11-dependent signaling pathway for p53
      stabilization.

PMID- 20056614
TI  - Generic approach for the generation of stable humanized single-chain Fv fragments
      from rabbit monoclonal antibodies.
AB  - Despite their favorable pharmacokinetic properties, single-chain Fv antibody
      fragments (scFvs) are not commonly used as therapeutics, mainly due to generally
      low stabilities and poor production yields. In this work, we describe the
      identification and optimization of a human scFv scaffold, termed FW1.4, which is
      suitable for humanization and stabilization of a broad variety of rabbit antibody
      variable domains. A motif consisting of five structurally relevant framework
      residues that are highly conserved in rabbit variable domains was introduced into
      FW1.4 to generate a generically applicable scFv scaffold, termed FW1.4gen.
      Grafting of complementarity determining regions (CDRs) from 15 different rabbit
      monoclonal antibodies onto FW1.4 and their derivatives resulted in humanized
      scFvs with binding affinities in the range from 4.7 x 10(-9) to 1.5 x 10(-11) m.
      Interestingly, minimalistic grafting of CDRs onto FW1.4gen, without any
      substitutions in the framework regions, resulted in affinities ranging from 5.7 x
      10(-10) to <1.8 x 10(-12) m. When compared with progenitor rabbit scFvs,
      affinities of most humanized scFvs were similar. Moreover, in contrast to
      progenitor scFvs, which were difficult to produce, biophysical properties of the
      humanized scFvs were significantly improved, as exemplified by generally good
      production yields in a generic refolding process and by apparent melting
      temperatures between 53 and 86 degrees C. Thus, minimalistic grafting of rabbit
      CDRs on the FW1.4gen scaffold presents a simple and reproducible approach to
      humanize and stabilize rabbit variable domains.

PMID- 20056617
TI  - Prostate cancer risk allele specific for African descent associates with
      pathologic stage at prostatectomy.
AB  - PURPOSE: A region on chromosome 8q24 was recently identified as a novel prostate
      cancer risk locus. Inherited variation in this region is associated with prostate
      cancer risk in the general population (21-58%), and specific alleles show a
      strong association in African-American men. This study was designed to evaluate
      associations between 8q24 risk alleles and clinical variables, such as pathologic
      stage, age at diagnosis, and recurrence, in a case series of African-American
      men. EXPERIMENTAL DESIGN: Peripheral blood DNA samples from 114 African-American
      men with prostate cancer, including 106 who had undergone radical prostatectomy,
      were genotyped for six single-nucleotide polymorphisms on three 8q24 regions. The
      presence of these single-nucleotide polymorphisms was compared with
      clinicopathologic and follow-up data after radical prostatectomy. RESULTS: The
      mean age of diagnosis and follow-up time were 57.4 (+/-8.9) years and 49.1 (+/
      31.6) months, respectively. Patients carrying the Broad11934905 A risk allele,
      which is specific for African ancestry, were more likely to have a higher
      pathologic stage (pT(3-4)) than individuals with the wild type (odds ratio, 4.48;
      95% confidence interval, 1.42-14.14; P = 0.011). A trend toward increased
      frequency of and shorter time to biochemical recurrence was noted in patients
      with this risk allele on Kaplan-Meier unadjusted survival analysis (P = 0.076).
      CONCLUSIONS: The Broad11934905 polymorphism at 8q24, which is only found in
      people of African ancestry, is associated with an increase in non-organ-confined
      prostate cancer at prostatectomy. In addition, for those with this risk allele,
      there is a trend toward early biochemical recurrence that requires validation in
      larger studies.

PMID- 20056615
TI  - Direct interaction of the bacteriophage SPP1 packaging ATPase with the portal
      protein.
AB  - DNA packaging in tailed bacteriophages and other viruses requires assembly of a
      complex molecular machine at a specific vertex of the procapsid. This machine is
      composed of the portal protein that provides a tunnel for DNA entry, an ATPase
      that fuels DNA translocation (large terminase subunit), and most frequently, a
      small terminase subunit. Here we characterized the interaction between the
      terminase ATPase subunit of bacteriophage SPP1 (gp2) and the procapsid portal
      vertex. We found, by affinity pulldown assays with purified proteins, that gp2
      interacts with the portal protein, gp6, independently of the terminase small
      subunit gp1, DNA, or ATP. The gp2-procapsid interaction via the portal protein
      depends on gp2 concentration and requires the presence of divalent cations.
      Competition experiments showed that isolated gp6 can only inhibit gp2-procapsid
      interactions and DNA packaging at gp6:procapsid molar ratios above 10-fold.
      Assays with gp6 carrying mutations in distinct regions of its structure that
      affect the portal-induced stimulation of ATPase and DNA packaging revealed that
      none of these mutations impedes gp2-gp6 binding. Our results demonstrate that the
      SPP1 packaging ATPase binds directly to the portal and that the interaction is
      stronger with the portal embedded in procapsids. Identification of mutations in
      gp6 that allow for assembly of the ATPase-portal complex but impair DNA packaging
      support an intricate cross-talk between the two proteins for activity of the DNA
      translocation motor.

PMID- 20056618
TI  - Diabetes and outcomes after radical prostatectomy: are results affected by
      obesity and race? Results from the shared equal-access regional cancer hospital
      database.
AB  - BACKGROUND: Diabetes is associated with lower prostate cancer risk. The
      association of diabetes with prostate cancer outcomes is less clear. We examined
      the association between diabetes and outcomes after radical prostatectomy and
      tested whether associations varied by race and/or obesity. MATERIALS AND METHODS:
      This study is a retrospective analysis of 1,262 men treated with radical
      prostatectomy between 1988 and 2008 within the Shared Equal-Access Regional
      Cancer Hospital database. We examined the multivariate association between
      diabetes at surgery and adverse pathology, biochemical recurrence (BCR), and
      prostate-specific antigen doubling time at recurrence using logistic,
      proportional hazards, and linear regression, respectively. Data were examined as
      a whole and stratified by race and obesity. RESULTS: Diabetes was more prevalent
      among black (22% versus 15%, P < 0.001) and more obese men (P < 0.001). Diabetes
      was associated with higher tumor grade (odds ratio, 1.73; P = 0.002), seminal
      vesicle invasion (odds ratio, 1.73; P = 0.04), but not BCR (P = 0.67) or PSADT at
      recurrence (P = 0.12). In the secondary analysis, among white obese men, diabetes
      was associated with 2.5-fold increased BCR risk (P = 0.002) and a trend toward
      shorter PSADT, whereas among all other men (nonobese white men and black men),
      diabetes was associated with 23% lower recurrence risk (P = 0.09) and longer
      PSADT (P = 0.04). CONCLUSION: In a radical prostatectomy cohort, diabetes was not
      associated with BCR. In the secondary analysis, diabetes was associated with more
      aggressive disease in obese white men and less aggressive disease for all other
      subsets. If externally validated, these findings suggest that among men with
      prostate cancer, the association between diabetes and prostate cancer
      aggressiveness may vary by race and obesity.

PMID- 20056619
TI  - Nutrient-based dietary patterns and laryngeal cancer: evidence from an
      exploratory factor analysis.
AB  - BACKGROUND: The issue of diet and laryngeal cancer has been rarely addressed
      considering the potential role of dietary patterns. METHODS: We examined this
      association using data from a case-control study carried out between 1992 and
      2000. Cases were 460 histologically confirmed incident laryngeal cancers
      hospitalized in two Italian areas. Controls were 1,088 subjects hospitalized for
      acute nonneoplastic diseases unrelated to tobacco or alcohol consumption. Dietary
      habits were investigated through a 78-item food frequency questionnaire. A
      posteriori dietary patterns were identified through principal component factor
      analysis carried out on a selected set of 28 major nutrients. The internal
      reproducibility, robustness, and reliability of the identified patterns were
      evaluated. Odds ratios (OR) of laryngeal cancer and 95% confidence intervals (95%
      CI) were estimated using unconditional multiple logistic regression models on
      quartiles of factor scores. RESULTS: We identified five major dietary patterns
      named "animal products," "starch-rich," "vitamins and fiber," "vegetable
      unsaturated fatty acids," and "animal unsaturated fatty acids." The vitamins and
      fiber dietary pattern was inversely associated with laryngeal cancer (OR, 0.35;
      95% CI, 0.24-0.52 for the highest versus the lowest score quartile), whereas the
      animal products (OR, 2.34; 95% CI, 1.59-3.45) and the animal unsaturated fatty
      acids (OR, 2.07; 95% CI, 1.42-3.01) patterns were directly associated with it.
      There was no significant association between the vegetable unsaturated fatty
      acids and the starch-rich patterns and laryngeal cancer risk. CONCLUSION: These
      findings suggest that diets rich in animal products and animal fats are directly
      related, and those rich in fruit and vegetables inversely related, to laryngeal
      cancer risk.

PMID- 20056620
TI  - Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as
      risk factors for gastric adenocarcinoma in the European prospective investigation
      into cancer and nutrition.
AB  - B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon
      metabolism may affect DNA synthesis and methylation and thereby be implicated in
      carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms
      other than those involving MTHFR as risk factors for gastric cancer (GC) are
      sparse and inconsistent. In this case-control study nested within the European
      Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and
      controls (n = 601) were matched for study center, age, sex, and time of blood
      sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin
      and flavin mononucleotide was used as the main exposure variable for vitamin B2
      status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic
      acid was used to define vitamin B6 status. In addition, we determined eight
      polymorphisms related to one-carbon metabolism. Relative risks for GC risk were
      calculated with conditional logistic regression, adjusted for Helicobacter pylori
      infection status and smoking status. Adjusted relative risks per quartile (95%
      confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and
      0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in
      individuals with severe chronic atrophic gastritis. The polymorphisms were not
      associated with GC risk and did not modify the observed vitamin-cancer
      associations. In summary, results from this large European cohort study showed an
      inverse association between vitamin B2 and GC risk, which is borderline
      significant, and a significant inverse association between vitamin B6 and GC
      risk.

PMID- 20056621
TI  - Coffee, tea, caffeine intake, and risk of adult glioma in three prospective
      cohort studies.
AB  - Current data suggest that caffeinated beverages may be associated with lower risk
      of glioma. Caffeine has different effects on the brain, some of which could play
      a role in brain carcinogenesis, and coffee has been consistently associated with
      reduced risk of liver cancer, thus suggesting a potential anticarcinogenic
      effect. A total of 335 incident cases of gliomas (men, 133; women, 202) were
      available from three independent cohort studies. Dietary intake was assessed by
      food frequency questionnaires obtained at baseline and during follow-up. Cox
      proportional hazard models were used to estimate incidence rate ratios (RR) and
      95% confidence intervals (CI) between consumption of coffee, tea, carbonated
      beverages, caffeine, and glioma risk adjusting for age and total caloric intake.
      Estimates from each cohort were pooled using a random-effects model. Consumption
      of five or more cups of coffee and tea daily compared with no consumption was
      associated with a decrease risk of glioma (RR, 0.60; 95% CI, 0.41-0.87; P(trend)
      = 0.04). Inverse, although weaker, associations were also observed between
      coffee, caffeinated coffee, tea, and carbonated beverages and glioma risk. No
      association was observed between decaffeinated coffee and glioma risk. Among men,
      a statistically significant inverse association was observed between caffeine
      consumption and risk of glioma (RR, 0.46; 95% CI, 0.26-0.81; P(trend) = 0.03);
      the association was weaker among women. Our findings suggest that consumption of
      caffeinated beverages, including coffee and tea, may reduce the risk of adult
      glioma, but further research is warranted to confirm these findings in other
      populations.

PMID- 20056622
TI  - Breast cancer risk 55+ years after irradiation for an enlarged thymus and its
      implications for early childhood medical irradiation today.
AB  - BACKGROUND: Radiotherapy during childhood increases long-term cancer risk, but
      the risk from radiation as a result of relatively higher dose diagnostic
      procedures remains less well known. This study, which evaluates breast cancer
      incidence in a cohort treated with "lower dose" chest radiotherapy over 50 years
      ago, can assist with estimating lifetime breast cancer risk in young children
      exposed to radiation from procedures such as chest computed tomography (CT) or
      treatment with recent "lower dose" chest radiotherapy protocols. METHODS: A
      population-based, longitudinal cohort of subjects exposed to thymic irradiation
      during infancy from 1926 to 1957 and of their unexposed siblings was re
      established. Previously followed until 1987, we resurveyed cohort members from
      2004 to 2008. Poisson regression models compared breast cancer incidence rates
      between women in the cohort by treatment and dose category groups. RESULTS:
      Breast cancer occurred in 96 treated (mean breast dose, 0.71 Gy) and 57 untreated
      women during 159,459 person-years of follow-up. After adjusting for attained age
      and treatment/birth cohort, the rate ratio was 3.01 (2.18-4.21). The adjusted
      excess relative risk per Gy was 1.10 (95% confidence interval, 0.61-1.86).
      Traditional breast cancer risk factors did not contribute significantly to
      multivariate model fit. CONCLUSION: Our results show that at radiation doses
      between those received by the breast from chest CT and cancer therapy during
      early childhood, breast cancer incidence rates remain elevated >50 years after
      exposure. This implies that increased breast cancer risk will remain a lifelong
      concern in females treated during childhood with currently reduced radiotherapy
      doses and for infants receiving multiple chest CTs.

PMID- 20056623
TI  - Aspirin and other nonsteroidal anti-inflammatory drugs in relation to Hodgkin
      lymphoma risk in northern Denmark.
AB  - There are few known modifiable risk factors for Hodgkin lymphoma, but the recent
      finding of an inverse association between routine regular-strength aspirin use
      and Hodgkin lymphoma risk suggests that aspirin may protect against Hodgkin
      lymphoma development. To further investigate this association using prospectively
      collected data, we conducted a population-based case-control study in northern
      Denmark. A total of 478 incident Hodgkin lymphoma cases were identified in
      nationwide health-care databases from 1991 to 2008. Ten population controls were
      matched to each case on age, sex, and county using risk-set sampling. Use of
      aspirin, selective cyclooxygenase-2 inhibitors, and other nonsteroidal anti
      inflammatory drugs (NSAIDs) from 1989 to 2007 was ascertained by linkage to a
      population-based prescription database. Conditional logistic regression was used
      to estimate odds ratios for associations between medication use and risk of
      Hodgkin lymphoma. The odds ratio (95% confidence interval) for ever use (>2
      prescriptions) compared with never/rare use (< or =2 prescriptions) of low-dose
      aspirin was 0.7 (0.5-1.2). The association with low-dose aspirin use did not vary
      appreciably by recentness, duration, or intensity of use. Recent use (>2
      prescriptions in the 1-2 years before the index date), short-term use (<7 years),
      and medium/high-intensity use (> or =25% of duration of use covered by
      prescription) of selective cyclooxygenase-2 inhibitors or other NSAIDs was
      associated with increased Hodgkin lymphoma risk possibly due to prodromal
      symptoms among cases. In conclusion, our results provide some evidence of a
      protective effect of low-dose aspirin, but not other NSAIDs, against Hodgkin
      lymphoma development.

PMID- 20056624
TI  - Familial melanoma: a meta-analysis and estimates of attributable fraction.
AB  - Melanoma commonly clusters in families, and the recent identification of numerous
      genotypes predicting higher risks of melanoma has led to the widespread
      perception that this cancer is predominantly a genetic disease. We conducted a
      systematic review of the literature and meta-analysis to quantify the
      contribution of familial factors 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 family history of the disease; we identified 22 such studies using
      citation databases, followed by manual review of retrieved references. We
      calculated summary RRs using weighted averages of the log RR, taking into account
      random effects, and used these to estimate the PAF. Overall, family history was
      associated with a significant 2-fold increased risk of melanoma (odds ratio,
      2.06; 95% confidence interval, 1.72-2.45); however, there was significant
      heterogeneity (P = 0.01). The pooled estimate for population-based studies (n =
      11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies
      (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013,
      respectively). Two studies used record linkage to verify family history in
      relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00)
      with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a
      positive family history ranged from 0.007 for Northern Europe to 0.064 for
      Australia (0.040 for all regions combined). Our findings suggest that only a
      small percentage of melanoma cases (always <7%) are attributable to familial
      risk; the majority of melanomas are presumably attributable to other factors.

PMID- 20056625
TI  - Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on
      invasive breast cancer.
AB  - BACKGROUND: The Women's Health Initiative dietary modification (DM) trial
      provided suggestive evidence of a benefit of a low-fat dietary pattern on breast
      cancer risk, with stronger evidence among women whose baseline diet was high in
      fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to
      breast cancer risk and could influence intervention effects. METHODS: All 48,835
      trial participants were postmenopausal and ages 50 to 79 years at enrollment
      (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676
      women who developed breast cancer during trial follow-up (1993-2005). Case-only
      analyses were used to estimate odds ratios for the DM intervention in relation to
      SNP genotype. RESULTS: Odds ratios for the DM intervention did not vary
      significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18).
      However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs,
      among women having baseline percent of energy from fat in the upper quartile (>
      or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios
      for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence
      intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33
      1.15). The nominal significance level for this interaction is P = 0.005, and P =
      0.03 following multiple testing adjustment, with most evidence deriving from
      hormone receptor-positive tumors. CONCLUSION: Invasive breast cancer odds ratios
      for a low-fat dietary pattern, among women whose usual diets are high in fat,
      seem to vary with SNP rs3750817 in the FGFR2 gene.

PMID- 20056626
TI  - Occupational exposure to formaldehyde, hematotoxicity, and leukemia-specific
      chromosome changes in cultured myeloid progenitor cells.
AB  - There are concerns about the health effects of formaldehyde exposure, including
      carcinogenicity, in light of elevated indoor air levels in new homes and
      occupational exposures experienced by workers in health care, embalming,
      manufacturing, and other industries. Epidemiologic studies suggest that
      formaldehyde exposure is associated with an increased risk of leukemia. However,
      the biological plausibility of these findings has been questioned because limited
      information is available on the ability of formaldehyde to disrupt hematopoietic
      function. Our objective was to determine if formaldehyde exposure disrupts
      hematopoietic function and produces leukemia-related chromosome changes in
      exposed humans. We examined the ability of formaldehyde to disrupt hematopoiesis
      in a study of 94 workers in China (43 exposed to formaldehyde and 51 frequency
      matched controls) by measuring complete blood counts and peripheral
      stem/progenitor cell colony formation. Further, myeloid progenitor cells, the
      target for leukemogenesis, were cultured from the workers to quantify the level
      of leukemia-specific chromosome changes, including monosomy 7 and trisomy 8, in
      metaphase spreads of these cells. Among exposed workers, peripheral blood cell
      counts were significantly lowered in a manner consistent with toxic effects on
      the bone marrow and leukemia-specific chromosome changes were significantly
      elevated in myeloid blood progenitor cells. These findings suggest that
      formaldehyde exposure can have an adverse effect on the hematopoietic system and
      that leukemia induction by formaldehyde is biologically plausible, which
      heightens concerns about its leukemogenic potential from occupational and
      environmental exposures.

PMID- 20056628
TI  - Arsenic in drinking water and risk of urinary tract cancer: a follow-up study
      from northeastern Taiwan.
AB  - The evidence linking arsenic in drinking water with increased urinary cancer risk
      comes from populations in relatively high exposure areas (>100 microg/L), whereas
      studies from lower exposure areas (<100 microg/L) reported inconsistent results.
      A previous study conducted in northeastern Taiwan, where residents were exposed
      to relatively lower concentrations, reported increased risk of urinary cancer in
      a dose-response way. Using the same cohort with longer follow-up, we conducted
      analysis to elucidate the relationship between ingested arsenic and urinary
      cancer in lower exposure groups and assessed the influence of duration, recency,
      and latency of drinking arsenic-containing well water. A total of 8,086 residents
      from northeastern Taiwan were followed for 12 years. Incident urinary cancer was
      ascertained through linkage with the national cancer registry. All analysis was
      done by Cox proportional hazards regression models. There were 45 incidences of
      urinary cancer and a monotonic increased risk of urinary cancer was found with
      increasing arsenic concentration (P < 0.001). For the highly exposed (>100
      microg/L), the relative risks (RR) were >5-fold, whereas the risk was elevated
      but not significant for low exposure (<100 microg/L). Relative to the arsenic
      concentration <10 microg/L, those who drank well water with higher concentration
      from birth [RR, 3.69; 95% confidence interval (95% CI), 1.31-10.4], still drank
      at enrollment (RR, 3.50; 95% CI, 1.33-9.22), and drank for >50 years (RR, 4.12;
      95% CI, 1.48-11.5) had a significantly increased risk of urinary cancer. When
      restricted to urothelial carcinoma, all risk estimates including concentration
      and characteristics of well water consumption were higher.

PMID- 20056627
TI  - Genetic variability in the MTHFR gene and colorectal cancer risk using the
      colorectal cancer family registry.
AB  - BACKGROUND: The MTHFR C677T TT genotype is associated with a 15% to 18% reduction
      in colorectal cancer risk, but it is not clear if other variants of the gene are
      associated with colorectal cancer risk. METHODS: We used a tagSNP approach to
      comprehensively evaluate associations between variation in the MTHFR gene and
      colorectal cancer risk using a large family-based case-control study of 1,750
      population-based and 245 clinic-based families from the Colon Cancer Family
      Registry. We assessed 22 TagSNPs, selected based on pairwise r(2) >95%, using the
      Haploview Tagger and genotyped the TagSNPs on the Illumina GoldenGate or Sequenom
      platforms. The association between single nucleotide polymorphisms and colorectal
      cancer was assessed using log-additive, codominant, and recessive models.
      RESULTS: From studying the population-based families, the C677T (rs1801133) and
      A1298C (rs1801131) polymorphisms were associated with a decreased colorectal
      cancer risk overall [odds ratio (OR), 0.81; 95% confidence interval (95% CI),
      0.63-1.04; and OR, 0.82; 95% CI, 0.64-1.07, respectively]. The 677 TT genotype
      was associated with a decreased risk of microsatellite-stable/microsatellite-low
      tumors (OR, 0.69; 95% CI, 0.49-0.97) and an increased risk of microsatellite-high
      tumors (OR, 2.22; 95% CI, 0.91-5.43; P(interaction) = 0.01), as well as an
      increased risk of proximal cancers and a decreased risk of distal and rectal
      cancers (P(interaction) = 0.02). No other single nucleotide polymorphism was
      associated with risk overall or within subgroups. CONCLUSION: The 677 TT and 1298
      CC genotypes may each be associated with a decrease in colorectal cancer risk. We
      observed little evidence of additional genetic variability in the MTHFR gene
      relevant to colorectal cancer risk.

PMID- 20056629
TI  - Sun and solarium exposure and melanoma risk: effects of age, pigmentary
      characteristics, and nevi.
AB  - BACKGROUND: Few prospective studies have analyzed solar and artificial (solarium)
      UV exposure and melanoma risk. We investigated these associations in a Norwegian
      Swedish cohort study and addressed effect modification by age, pigmentary
      characteristics, and nevi. METHODS: The cohort included women ages 30 to 50 years
      at enrollment from 1991 to 1992. Host factors and exposure to sun and solariums
      in life decades were collected by questionnaire at enrollment. Relative risks
      (RR) with 95% confidence intervals (CI) were estimated by Poisson regression.
      RESULTS: Among 106,366 women with complete follow-up through 2005, 412 melanoma
      cases were diagnosed. Hair color and large, asymmetric nevi on the legs were
      strongly associated with melanoma risk (P(trend) < 0.001), and the RR for > or =2
      nevi increased from brown/black to blond/yellow to red-haired women (RRs, 1.72,
      3.30, and 4.95, respectively; P(interaction) = 0.18). Melanoma risk increased
      significantly with the number of sunburns and bathing vacations in the first
      three age decades (P(trend) < or = 0.04) and solarium use at ages 30 to 39 and 40
      to 49 years [RRs for solarium use > or =1 time/mo 1.49 (95% CI, 1.11-2.00) and
      1.61 (95% CI 1.10-2.35), respectively; P(trend) < or = 0.02]. Risk of melanoma
      associated with sunburns, bathing vacations, and solarium use increased with
      accumulating exposure across additional decades of life. CONCLUSIONS: Melanoma
      risk seems to continue to increase with accumulating intermittent sun exposure
      and solarium use in early adulthood. Apparently, super-multiplicative joint
      effects of nevi and hair color identify people with red hair and multiple nevi as
      a very high risk group and suggest important gene-gene interactions involving
      MC1R in melanoma etiology.

PMID- 20056630
TI  - Influence of high-dose estrogen exposure during adolescence on mammographic
      density for age in adulthood.
AB  - High-dose estrogen exposure during adolescence has been hypothesized to increase
      a woman's breast cancer risk, possibly mediated through an increase in
      mammographic density, a well-established breast cancer risk factor. In 2006 to
      2007, we conducted a retrospective study of women assessed for tall stature as an
      adolescent between 1959 and 1993. Eligible participants were ages > or =40 years
      and treated during adolescence with 3 mg diethylstilbestrol or 150 microg ethinyl
      estradiol daily or untreated. Mammograms from 167 treated and 142 untreated women
      were digitized. Total breast area, dense area, nondense area, and percent density
      were measured using a computer thresholding technique. Data on potential
      determinants were collected from medical records and telephone interview. Treated
      women had, on average, 17% lower dense area (P = 0.032). Means (95% confidence
      intervals) adjusted for age and body mass index for treated and untreated women
      were 24.5 cm(2) (21.8-27.2) and 29.1 cm(2) (26.0-32.4), respectively. There was
      no difference in adjusted means (95% confidence intervals) between treated and
      untreated women for nondense area [71.7 cm(2) (66.2-77.7) versus 70.5 cm(2) (64.7
      76.9); P = 0.78], percent dense area [24.8% (22.4-27.4) versus 27.7% (24.8-30.7);
      P = 0.16], or total area [105.6 cm(2) (100.1-111.4) versus 109.3 cm(2) (103.1
      115.8); P = 0.41], respectively. High-dose estrogen exposure during adolescence
      appears to curtail growth of mammographically dense tissue and therefore is
      unlikely to increase breast cancer risk through mechanisms related to
      mammographic density.

PMID- 20056631
TI  - Plasma 25-hydroxyvitamin D levels and the risk of colorectal cancer: the
      multiethnic cohort study.
AB  - Vitamin D is obtained from the diet and synthesized in skin exposed to sunlight.
      Vitamin D status, assessed by circulating 25-hydroxyvitamin D [25(OH)D], has been
      associated with a reduced risk of colorectal cancer in previous studies. To
      complement existing evidence, we conducted a case-control study nested within the
      Multiethnic Cohort including men and women of Japanese, Latino, African-American,
      White, and Native Hawaiian ancestry. Using a direct competitive chemiluminescence
      immunoassay, 25(OH)D level was determined in plasma drawn before diagnosis from
      229 cases and 434 controls matched to cases by area (Hawaii, Los Angeles), sex,
      ethnicity, birth year, blood draw date and time, and hours fasting. Odds ratios
      (OR) were estimated with conditional logistic regression. An inverse trend was
      observed (OR per doubling of 25(OH)D, 0.68; 95% confidence interval, 0.51-0.92; P
      = 0.01), but when examined in categories, relative to the first quintile (<16.8
      ng/mL), the ORs in all other quintiles were quite similarly reduced between 37%
      and 46%. The association was not significantly heterogeneous among the four
      largest ethnic groups (P(heterogeneity) = 0.46). In summary, this study provides
      evidence of an association between vitamin D status and reduced risk of
      colorectal cancer in an ethnically diverse population.

PMID- 20056632
TI  - Dietary glucosinolate intake, polymorphisms in selected biotransformation
      enzymes, and risk of prostate cancer.
AB  - A protective role of glucosinolates in prostate cancer development might be
      mediated by the induction of biotransformation enzymes. These enzymes, enhancing
      the elimination of carcinogens from the body, are known to be polymorphic.
      Therefore, we evaluated whether a possible association between glucosinolate
      intake and prostate cancer risk is modified by polymorphisms in GSTT1, GSTM1,
      GSTA1, GSTP1, or NOQ1 genes. A case-control study including 248 prostate cancer
      cases and 492 matched controls was nested in the prospective European Prospective
      Investigation into Cancer and Nutrition-Heidelberg cohort. At baseline,
      participants provided dietary and lifestyle data and blood samples, which were
      used for genotyping and measurement of serum glutathione S-transferase-alpha
      concentration. Odds ratios and 95% confidence intervals were calculated by
      conditional logistic regression. We found an inverse association of glucosinolate
      intake with prostate cancer risk (adjusted odds ratio, 0.72 per 10 mg/d
      increment; 95% confidence interval, 0.53-0.96). Stratification by genotype showed
      significantly reduced risks for subjects with wild-type of NQO1 (C609T) compared
      with CT or TT carriers (P(interaction) = 0.04). Those with deletions in both
      GSTM1 and GSTT1 genes combined had a significantly reduced risk with increasing
      glucosinolate intake (P(interaction) = 0.01). There was no effect modification of
      glucosinolate intake and cancer risk by GSTA1 (G-52A) or GSTP1 (A313G) genotype,
      but serum glutathione S-transferase-alpha concentrations were inversely
      associated with prostate cancer. This study showed that the inverse association
      between glucosinolate intake and prostate cancer risk was modified by NQO1
      (C609T) and GSTM1 and GSTT1 deletion polymorphisms. This information will help to
      further elucidate the mechanism of action of potentially protective substances in
      vivo.

PMID- 20056633
TI  - Feasibility study for collection of HER2 data by National Cancer Institute (NCI)
      Surveillance, Epidemiology, and End Results (SEER) Program central cancer
      registries.
AB  - The clinical importance of human epidermal growth factor receptor-2 (HER2) in
      breast cancer is now clearly established, given that expression of this tumor
      marker is used to guide therapy and as a prognostic indicator. Despite its now
      routine evaluation in breast cancer patients, population-based data are lacking
      because information on HER2 status is not routinely collected in the majority of
      population-based cancer registries. We assessed the feasibility of collecting
      HER2 data and its completeness in three registries in the Surveillance
      Epidemiology and End Results (SEER) Program. Among a sample of invasive first
      primary breast cancer patients diagnosed between June and December 2007, HER2
      tests had been done on 96.5% (n = 522), and test results were available for 95.2%
      (n = 515) of patients. The majority of HER2 tests were performed by
      immunohistochemistry alone (50.9%), 35.3% by both immunohistochemistry and
      fluorescence in situ hybridization (FISH), and 11.8% of tests by FISH alone. As a
      result of these findings, SEER registries will collect HER2 data on all invasive
      breast cancer patients as an optional data element for those diagnosed in 2009
      and HER2 will likely be a required data element for these patients in 2010.

PMID- 20056634
TI  - Soy consumption and colorectal cancer risk in humans: a meta-analysis.
AB  - The purpose of the present study was to determine the relationship between soy
      consumption and colorectal cancer risk in humans by conducting a meta-analysis of
      available epidemiologic studies. We systematically reviewed publications obtained
      through a Medline literature search and identified four cohort and seven case
      control studies on soy and colorectal cancer risk that met the inclusion
      criteria. We extracted the risk estimate (hazard ratio, relative risk, or odds
      ratio) of the highest and the lowest reported categories of intake from each
      study and conducted this analysis using a random-effects model. Our analysis did
      not find that soy consumption was associated with colorectal cancer risk
      [combined risk estimate, 0.90; 95% confidence interval (95% CI), 0.79-1.03] nor
      did the separate analyses on colon cancer (combined risk estimate, 0.88; 95% CI,
      0.74-1.06) and rectal cancer (combined risk estimate, 0.88; 95% CI, 0.67-1.14).
      However, when separately analyzed on the basis of gender, we found that soy was
      associated with an approximately 21% reduction in colorectal cancer risk in women
      (combined risk estimate, 0.79; 95% CI, 0.65-0.97; P = 0.026), but not in men
      (combined risk estimate, 1.10; 95% CI, 0.90-1.33). Thus, consumption of soy foods
      may be associated with a reduction in colorectal cancer risk in women, but not in
      men.

PMID- 20056635
TI  - Marginal and mixed-effects models in the analysis of human papillomavirus natural
      history data.
AB  - Human papillomavirus (HPV) natural history has several characteristics that, at
      least from a statistical perspective, are not often encountered elsewhere in
      infectious disease and cancer research. There are, for example, multiple HPV
      types, and infection by each HPV type may be considered separate events. Although
      concurrent infections are common, the prevalence, incidence, and
      duration/persistence of each individual HPV can be separately measured. However,
      repeated measures involving the same subject tend to be correlated. The
      probability of detecting any given HPV type, for example, is greater among
      individuals who are currently positive for at least one other HPV type. Serial
      testing for HPV over time represents a second form of repeated measures.
      Statistical inferences that fail to take these correlations into account would be
      invalid. However, methods that do not use all the data would be inefficient.
      Marginal and mixed-effects models can address these issues but are not frequently
      used in HPV research. The current study provides an overview of these methods and
      then uses HPV data from a cohort of HIV-positive women to illustrate how they may
      be applied, and compare their results. The findings show the greater efficiency
      of these models compared with standard logistic regression and Cox models.
      Because mixed-effects models estimate subject-specific associations, they
      sometimes gave much higher effect estimates than marginal models, which estimate
      population-averaged associations. Overall, the results show that marginal and
      mixed-effects models are efficient for studying HPV natural history, but also
      highlight the importance of understanding how these models differ.

PMID- 20056636
TI  - Cardiovascular risk factors in adult survivors of pediatric cancer--a report from
      the childhood cancer survivor study.
AB  - BACKGROUND: Childhood cancer survivors are at higher risk of morbidity and
      mortality from cardiovascular disease compared with the general population.
      METHODS: Eight thousand five hundred ninety-nine survivors (52% male) and 2,936
      siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively
      ascertained, prospectively followed study of persons who survived 5 years after
      childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index
      of > or =30 kg/m(2) based on self-reported heights and weights and self-reported
      use of medications for hypertension, dyslipidemia, and impaired glucose
      metabolism. The presence of three or more of the above constituted Cardiovascular
      Risk Factor Cluster (CVRFC), a surrogate for Metabolic Syndrome. RESULTS:
      Survivors were more likely than siblings to take medications for hypertension
      [odds ratio (OR), 1.9; 95% confidence interval (95% CI), 1.6-2.2], dyslipidemia
      (OR, 1.6; 95% CI, 1.3-2.0) or diabetes (OR, 1.7; 95% CI, 1.2-2.3). Among these
      young adults (mean age of 32 years for survivors and 33 years for siblings),
      survivors were not more likely than siblings to be obese or have CVRFC. In a
      multivariable logistic regression analysis, factors associated with having CVRFC
      included older age at interview [> or =40 versus <30 years of age (OR, 8.2; 95%
      CI, 3.5-19.9)], exposure to total body irradiation (OR, 5.5; 95% CI, 1.5-15.8) or
      radiation to the chest and abdomen (OR, 2.3; 95% CI, 1.2-2.4), and physical
      inactivity (OR, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: Among adult survivors of
      pediatric cancer, older attained age, exposure to total body irradiation or
      abdominal plus chest radiation, and a sedentary life-style are associated with
      CVRFC.

PMID- 20056637
TI  - TD-GC-MS analysis of volatile metabolites of human lung cancer and normal cells
      in vitro.
AB  - The aim of this study was to confirm the existence of volatile organic compounds
      (VOC) specifically released or consumed by the lung cancer cell line A549, which
      could be used in future screens as biomarkers for the early detection of lung
      cancer. For comparison, primary human bronchial epithelial cells (HBEpC) and
      human fibroblasts (hFB) were included. VOCs were detected in the headspace of
      cell cultures or medium controls following adsorption on solid sorbents,
      thermodesorption, and analysis by gas chromatography mass spectrometry. Using
      this approach, we identified VOCs that behaved similarly in normal and
      transformed cells. Thus, concentrations of 2-pentanone and 2,4-dimethyl-1-heptene
      were found to increase in the headspace of A549, HBEpC, and hFB cell cultures. In
      addition, the ethers methyl tert-butyl ether and ethyl tert-butyl ether could be
      detected at elevated levels in the case of A549 cells and one of the
      untransformed cell lines. However, especially branched hydrocarbons and alcohols
      were seen increased more frequently in untransformed than A549 cells. A big
      variety of predominantly aldehydes and the ester n-butyl acetate were found at
      decreased concentrations in the headspace of all cell lines tested compared with
      medium controls. Again, more different aldehydes were found to be decreased in
      hFB and HBEpC cells compared with A549 cells and 2-butenal was metabolized
      exclusively by both control cell lines. These data suggest that certain groups of
      VOCs may be preferentially associated with the transformed phenotype.

PMID- 20056638
TI  - Accuracy of self-reported reason for colorectal cancer testing.
AB  - Assessment of accuracy of self-reported reason for colorectal cancer testing has
      been limited. We examined the accuracy and correlates of self-reported reason
      (screening or diagnosis) for having a sigmoidoscopy or colonoscopy. Patients who
      had received at least one sigmoidoscopy or colonoscopy within the past 5 years
      were recruited from a large multispecialty clinic in Houston, TX, between 2005
      and 2007. We calculated concordance, positive predictive value, negative
      predictive value, sensitivity, and specificity between self-reported reason and
      the medical record (gold standard). Logistic regression was performed to identify
      correlates of accurate self-report. Self-reported reason for testing was more
      accurate when the sigmoidoscopy or colonoscopy was done for screening, rather
      than diagnosis. In the multivariable analysis for sigmoidoscopy, age was
      positively associated with accurately reporting reason for testing, whereas
      having two or more colorectal cancer tests during the study period (compared with
      only one test) was negatively associated with accuracy. In the multivariable
      analysis, none of the correlates was statistically associated with colonoscopy
      although a similar pattern was observed for number of tests. Determining the best
      way to identify those who have been tested for diagnosis, rather than screening,
      is an important next step.

PMID- 20056640
TI  - Genetic variants of nucleotide excision repair genes are associated with DNA
      damage in coke oven workers.
AB  - We explored the effects of single nucleotide polymorphisms (SNP) of nucleotide
      excision repair (NER) genes on DNA damage caused by exposure to carcinogenic
      polycyclic aromatic hydrocarbons (PAH) in 475 Chinese workers. We quantified
      urinary 1-hydroxypyrene using high-performance liquid chromatography, and the DNA
      damage level of lymphocytes was examined by the comet assay and represented as
      the Olive tail moment (OTM) value. We genotyped 38 tagSNPs in 10 NER genes. The
      SNP function was further investigated using luciferase reporter assay in three
      cell lines. Our results showed that two promoter SNPs, XPA rs1800975 and XPC
      rs3731055, were associated with lower OTM values (P(trend) = 0.01 and 0.02
      respectively). However, another missense SNP rs2228001 in the XPC gene was
      positively associated with OTM value (P(trend) = 0.01). A stratified analysis
      found that the association between this SNP and DNA damage was only observed
      among subjects with higher PAH exposure levels but not among those with lower
      exposure levels (P(interaction) = 0.018). A dose-response association was found
      between the combined risk alleles of the above three genetic variants and
      increased DNA damage levels (P(trend) = 0.004). This association was more
      pronounced in subjects with higher PAH exposure than those with lower exposure
      levels (P(interaction) = 0.046). Our functional study indicated that XPA
      rs1800975G and XPC rs3731055A alleles had a higher luciferase expression than
      their corresponding SNP alleles (P < 0.05). These results suggested that genetic
      variations in key NER genes, especially in XPA and XPC genes, may modulate DNA
      damage levels when exposed to PAHs.

PMID- 20056639
TI  - Randomized trial of a lay health advisor and computer intervention to increase
      mammography screening in African American women.
AB  - BACKGROUND: Low-income African American women face numerous barriers to
      mammography screening. We tested the efficacy of a combined interactive computer
      program and lay health advisor intervention to increase mammography screening.
      METHODS: In this randomized, single blind study, participants were 181 African
      American female health center patients of ages 41 to 75 years, at < or =250% of
      poverty level, with no breast cancer history, and with no screening mammogram in
      the past 15 months. They were assigned to either (a) a low-dose comparison group
      consisting of a culturally appropriate mammography screening pamphlet or (b)
      interactive, tailored computer instruction at baseline and four monthly lay
      health advisor counseling sessions. Self-reported screening data were collected
      at baseline and 6 months and verified by medical record. RESULTS: For intent-to
      treat analysis of primary outcome (medical record-verified mammography screening,
      available on all but two participants), the intervention group had increased
      screening to 51% (45 of 89) compared with 18% (16 of 90) for the comparison group
      at 6 months. When adjusted for employment status, disability, first-degree
      relatives with breast cancer, health insurance, and previous breast biopsies, the
      intervention group was three times more likely (adjusted relative risk, 2.7; 95%
      confidence interval, 1.8-3.7; P < 0.0001) to get screened than the low-dose
      comparison group. Similar results were found for self-reported mammography stage
      of screening adoption. CONCLUSIONS: The combined intervention was efficacious in
      improving mammography screening in low-income African American women, with an
      unadjusted effect size (relative risk, 2.84) significantly higher (P < 0.05) than
      that in previous studies of each intervention alone.

PMID- 20056641
TI  - Multiple genetic variants in telomere pathway genes and breast cancer risk.
AB  - PURPOSE: To explore the etiologic role of genetic variants in telomere pathway
      genes and breast cancer risk. METHODS: A population-based case-control study, the
      Long Island Breast Cancer Study Project, was conducted, and 1,067 cases and 1,110
      controls were included in the present study. Fifty-two genetic variants of nine
      telomere-related genes were genotyped. RESULTS: Seven single nucleotide
      polymorphisms (SNP) showed significant case-control differences at the level of P
      < 0.05. The top three statistically significant SNPs under a dominant model were
      TERT-07 (rs2736109), TERT-54 (rs3816659), and POT1-03 (rs33964002). The odds
      ratios (OR) were 1.56 [95% confidence interval (95% CI), 1.22-1.99] for the TERT
      07 G-allele, 1.27 (95% CI, 1.05-1.52) for the TERT-54 T-allele, and 0.79 (95% CI,
      0.67-0.95) for the POT1-03 A-allele. TERT-67 (rs2853669) was statistically
      significant under a recessive model; the OR of the CC genotype was 0.69 (95% CI,
      0.69-0.93) compared with the T-allele. However, none of the SNPs retained
      significance after Bonferroni adjustment for multiple testing at the level of P <
      0.001 (0.05/52) except for TERT-07. When restricted to Caucasians (94% of the
      study subjects), a stronger association for the TERT-07 G-allele was observed
      with an OR of 1.60 (95% CI, 1.24-2.05; P = 0.0002). No effect modifications were
      found for variant alleles and menopausal status, telomere length, cigarette
      smoking, body mass index status, and family history of breast cancer risk.
      CONCLUSIONS: Four SNPs in the TERT and POT1 genes were significantly related with
      overall breast cancer risk. This initial analysis provides valuable clues for
      further exploration of the biological role of telomere pathway genes in breast
      cancer.

PMID- 20056642
TI  - Genetic variation of genes involved in dihydrotestosterone metabolism and the
      risk of prostate cancer.
AB  - PURPOSE: Dihydrotestosterone (DHT) is an important factor in prostate cancer
      (PCA) genesis and disease progression. Given PCA's strong genetic component, we
      evaluated the possibility that variation in genes involved in DHT metabolism
      influence PCA risk. EXPERIMENTAL DESIGN: We investigated copy number variants
      (CNV) and single nucleotide polymorphisms (SNP). We explored associations between
      CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B
      subclass, given their prostate specificity and/or involvement in steroid
      metabolism and PCA risk. We also investigated associations between SNPs in genes
      (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT,
      and in DHT metabolism and PCA risk. The population consisted of 426 men (205
      controls and 221 cases) who underwent prostate-specific antigen screening as part
      of a PCA early detection program in Tyrol, Austria. RESULTS: No association
      between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the
      AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95%
      confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with
      AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13).
      Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when
      compared with men carrying neither (P = 0.005). Controls with the AA genotype on
      rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03). CONCLUSIONS:
      This is the first study to implicate the 5alpha-reductase isoform 1 (SRD5A1) and
      PCA risk, supporting the rationale of blocking enzymatic activity of both
      isoforms of 5alpha-reductase for PCA chemoprevention.

PMID- 20056643
TI  - A rigorous and comprehensive validation: common genetic variations and lung
      cancer.
AB  - BACKGROUND: Multiple recent genome-wide studies of single nucleotide
      polymorphisms (SNP) reported associations between candidate chromosome loci and
      lung cancer susceptibility. We evaluated five of the top candidate SNPs
      (rs402710, rs2736100, rs4324798, rs16969968, and rs8034191) for their effects on
      lung cancer risk and overall survival. METHODS: Over 1,700 cases and 2,200
      controls were included in this study. Seven independent, complementary case
      control data sets were tested for risk assessment encompassing cigarette smokers
      and never smokers, using unrelated controls and unaffected full-sibling controls.
      Five patient groups were tested for survival prediction stratified by smoking
      status, histology subtype, and treatment. RESULTS: After considering a history of
      chronic obstructive pulmonary disease as a risk factor altering lung cancer risk
      and comparing to sibling controls, none of the five SNPs remained significant.
      However, the variant rs4324798 was significant in predicting overall survival
      (hazard ratio, 0.46; 95% confidence interval, 0.30-0.73; P = 0.001) in small cell
      lung cancer. CONCLUSIONS: None of the five candidate SNPs in lung cancer risk can
      be confirmed in our study. The previously reported association could be explained
      by disparity in tobacco smoke exposure and chronic obstructive pulmonary disease
      history between cases and controls. Instead, we found rs4324798 to be an
      independent predictor in small cell lung cancer survival, warranting further
      elucidation of the underlying mechanisms.

PMID- 20056645
TI  - Association of mitotic regulation pathway polymorphisms with pancreatic cancer
      risk and outcome.
AB  - BACKGROUND: Mitosis is a highly regulated process that serves to ensure the
      fidelity of cell division. The disruption of mitotic regulators leading to
      aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide
      polymorphisms (SNP) in regulators of mitosis may promote chromosome
      missegregation and influence pancreatic cancer and/or survival. METHODS: Thirty
      four SNPs, previously associated with breast cancer risk, from 33 genes involved
      in the regulation of mitosis, were investigated for associations with pancreatic
      cancer risk in 1,143 Caucasian patients with pancreatic adenocarcinoma and 1,097
      unaffected controls from the Mayo Clinic. Associations with survival from
      pancreatic cancer were also assessed using 1,030 pancreatic cancer cases with
      known outcome. RESULTS: Two SNPs in the APC (rs2431238) and NIN (rs10145182)
      loci, of 34 examined, were significantly associated with pancreatic cancer risk
      (P = 0.035 and P = 0.038, respectively). Further analyses of individuals
      categorized by smoking and body mass index identified several SNPs displaying
      significant associations (P < 0.05) with pancreatic cancer risk, including APC
      rs2431238 in individuals with high body mass index (>/=30; P = 0.031) and NIN
      rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected
      significant associations between SNPs in EIF3S10 and overall survival (P =
      0.009), SNPs from five genes and survival in resected cancer cases (P < 0.05),
      and SNPs from two other genes (P < 0.05) and survival of locally advanced cancer
      cases. CONCLUSION: Common variation in genes encoding regulators of mitosis may
      independently influence pancreatic cancer susceptibility and survival.

PMID- 20056644
TI  - ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian
      Cancer Association Consortium study.
AB  - We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor
      alpha gene (ESR1) region in three population-based case-control studies of
      epithelial ovarian cancer conducted in the United States, comprising a total of
      1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A
      SNP 19 kb downstream of ESR1 (rs2295190, G-to-T change) was associated with
      invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95%
      confidence interval (CI), 1.06-1.44, P = 0.006]. rs2295190 is a nonsynonymous
      coding SNP in a neighboring gene called spectrin repeat containing, nuclear
      envelope 1 (SYNE1), which is involved in nuclear organization and structural
      integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded
      by SYNE1 has been reported to be downregulated in ovarian and other cancers.
      rs2295190 was genotyped in an additional 12 studies through the Ovarian Cancer
      Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls.
      The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P =
      0.017). Results for the serous subtype in the 15 combined studies were similar to
      those overall (n = 3,545; OR, 1.09; 95% CI, 1.01-1.18; P = 0.025), and our
      findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11
      1.58; P = 0.002). No association was observed for the endometrioid subtype. In an
      additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls,
      rs2295190 was not associated with risk. These data provide suggestive evidence
      that the rs2295190 T allele, or another allele in linkage disequilibrium with it,
      may be associated with increased risk of invasive ovarian cancer.

PMID- 20056646
TI  - Population-based study of the association of variants in mismatch repair genes
      with prostate cancer risk and outcomes.
AB  - BACKGROUND: Mismatch repair (MMR) gene activity may be associated with prostate
      cancer risk and outcomes. This study evaluated whether single nucleotide
      polymorphisms (SNP) in key MMR genes are related to prostate cancer outcomes.
      METHODS: Data from two population-based case-control studies of prostate cancer
      among Caucasian and African-American men residing in King County, Washington were
      combined for this analysis. Cases (n = 1,458) were diagnosed with prostate cancer
      in 1993 to 1996 or 2002 to 2005 and were identified through the Seattle-Puget
      Sound Surveillance Epidemiology and End Results cancer registry. Controls (n =
      1,351) were age-matched to cases and were identified through random digit
      dialing. Logistic regression was used to assess the relationship between
      haplotype-tagging SNPs and prostate cancer risk and disease aggressiveness. Cox
      proportional hazards regression was used to assess the relationship between SNPs
      and prostate cancer recurrence and prostate cancer-specific death. RESULTS:
      Nineteen SNPs were evaluated in the key MMR genes: five in MLH1, 10 in MSH2, and
      4 in PMS2. Among Caucasian men, one SNP in MLH1 (rs9852810) was associated with
      overall prostate cancer risk [odds ratio, 1.21; 95% confidence interval (95% CI),
      1.02, 1.44; P = 0.03], more aggressive prostate cancer (odds ratio, 1.49; 95% CI,
      1.15, 1.91; P < 0.01), and prostate cancer recurrence (hazard ratio, 1.83; 95%
      CI, 1.18, 2.86; P < 0.01), but not prostate cancer-specific mortality. A
      nonsynonymous coding SNP in MLH1, rs1799977 (I219V), was also found to be
      associated with more aggressive disease. These results did not remain significant
      after adjusting for multiple comparisons. CONCLUSION: This population-based case
      control study provides evidence for a possible association with a gene variant in
      MLH1 in relation to the risk of overall prostate cancer, more aggressive disease,
      and prostate cancer recurrence, which warrants replication.

PMID- 20056647
TI  - Gene methylation in breast ductal fluid from BRCA1 and BRCA2 mutation carriers.
AB  - PURPOSE: Genomic alterations (including gene hypermethylation) are likely to
      precede the phenotypic changes associated with breast tumorigenesis. From a
      prospective collection of ductal lavage (DL) samples from women with a known
      mutation in BRCA1 or BRCA2, we have assessed promoter methylation with a
      comparison of results with several variables, including breast cancer (BC)
      outcome. EXPERIMENTAL DESIGN: Hypermethylation of p16, RASSF1A, twist, and
      RARbeta was assessed using a qualitative, real-time, nested PCR assay.
      Associations between methylation status and variables were tested using Fisher's
      exact test or logistic regression. Analyses were done at three levels: a single
      breast, a single duct (both over time), and each DL sample in isolation. RESULTS:
      A total of 168 samples from 93 ducts in 54 breasts have been analyzed in 34 women
      (16 BRCA1 and 18 BRCA2 mutation carriers). A median of 2 DL was done (range, 1
      5), with 7 women developing BC on study, 1 bilateral. Methylation of p16 was
      associated with a known BRCA1 mutation (P = 0.001, P < 0.001, and P < 0.001 for
      breast, duct, and sample levels, respectively) and women with a history of
      contralateral BC (P = 0.001 and P < 0.001 for duct and sample levels,
      respectively). An association was seen for women who developed BC on study and
      RASSF1A methylation (P = 0.001 for sample level). CONCLUSIONS: Genetic
      methylation patterns could potentially be used to predict future BC risk. In
      addition, p16 methylation may be a predictor of BRCA1 mutation status. Further
      research is required to corroborate these findings.

PMID- 20056648
TI  - Patterns of sex steroid hormones in nipple aspirate fluid during the menstrual
      cycle and after menopause in relation to serum concentrations.
AB  - Previous studies have shown that progesterone concentrations in serum and nipple
      aspirate fluid (NAF) are significantly correlated in premenopausal women, but
      estradiol concentrations are not. We therefore sought to ascertain the patterns
      of both steroids in NAF throughout the menstrual cycle and in postmenopausal
      women. Simultaneous samples of blood and NAF were obtained from 40 premenopausal
      and 16 postmenopausal women. Premenopausal samples were backdated from the
      following menstrual period. Steroids were purified by high-performance liquid
      chromatography before quantification by immunoassays. Serum steroids and NAF
      progesterone followed the expected pattern across the menstrual cycle, with a
      midcycle peak of estradiol and a midluteal peak of progesterone. However, the
      estradiol peak in NAF occurred about a week after the serum peak in the midluteal
      phase, when serum estradiol had declined to less than half the value at midcycle.
      NAF estrone was also elevated at the midluteal phase. Potential estrogen
      precursors androstenedione, estrone sulfate, and dehydroepiandrosterone sulfate
      declined in NAF from midcycle to the midluteal phase as NAF estradiol was
      increasing. Progesterone concentrations were significantly lower in NAF in
      postmenopausal women than in premenopausal women, but estrogen concentrations
      were not. This is the first description of the temporal relationships of sex
      steroids in NAF and serum relative to the menstrual cycle. These results provide
      insights into the lack of correlation of NAF and breast tissue estrogens with
      serum estrogens, and generate new hypotheses.

PMID- 20056649
TI  - Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in
      normal colorectal mucosa: a randomized clinical trial.
AB  - The exact antineoplastic effects of calcium and vitamin D(3) in the human colon
      are unclear. Animal and in vitro studies show that these two agents reduce
      oxidative stress; however, these findings have never been investigated in humans.
      To address this, we conducted a pilot, randomized, double-blind, placebo
      controlled, 2 x 2 factorial clinical trial to test the effects of calcium and
      vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8
      OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one
      pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800
      IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal
      crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were
      detected by standardized automated immunohistochemistry and quantified by image
      analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of
      colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium
      and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3)
      group. The estimated treatment effects were strongest among participants with
      higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall,
      these preliminary results indicate that calcium and vitamin D(3) may decrease
      oxidative DNA damage in the normal human colorectal mucosa, support the
      hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative
      DNA damage biomarker of risk for colorectal neoplasms, and provide support for
      further investigation of calcium and vitamin D(3) as chemopreventive agents
      against colorectal neoplasms.

PMID- 20056650
TI  - Comparison of liquid chromatography-tandem mass spectrometry, RIA, and ELISA
      methods for measurement of urinary estrogens.
AB  - Absolute and relative concentrations of estrogens and estrogen metabolites are
      important for clinical decisions as well as for epidemiologic, experimental, and
      clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used
      for measuring estrogen metabolites in blood and urine due to efficiency and low
      cost. Here, we compare absolute and ranked concentrations of estrone, estradiol,
      and estriol measured by indirect RIA and of 2-hydroxyestrone and 16alpha
      hydroxyestrone measured by ELISA to the concentrations obtained using a novel
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures
      15 estrogen metabolites concurrently. We used overnight urine samples collected
      from control women (362 premenopausal and 168 postmenopausal) participating in a
      population-based case-control study of breast cancer among Asian American women
      ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute
      concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4
      to 11.8 times higher in premenopausal and postmenopausal women, respectively (all
      P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r
      (r(s)) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and
      moderately correlated (r(s) = 0.4-0.8) in postmenopausal women. Measurements of
      the 2-hydroxyestrone:16alpha-hydroxyestrone ratio, a putative biomarker of breast
      cancer risk, were moderately correlated in premenopausal women (r(s) = 0.6-0.7)
      but only weakly correlated in postmenopausal women (r(s) = 0.2). LC-MS/MS had
      higher intraclass correlation coefficients (> or =99.6%) and lower coefficients
      of variation (< or =9.4%) than ELISA (> or =97.2% and < or =14.2%) and RIA (> or
      =95.2% and < or =17.8%). Comparison with the LC-MS/MS method suggests that the
      widely used RIA and ELISA estrogen metabolite measures may be problematic,
      especially at low estrogen metabolite levels characteristic of postmenopausal
      women.

PMID- 20056651
TI  - Cytoplasmic localization of beta-catenin is a marker of poor outcome in breast
      cancer patients.
AB  - Beta-catenin is involved in cell adhesion through catenin-cadherin complexes and
      as a transcriptional regulator in the Wnt signaling pathway. Its deregulation is
      important in the genesis of a number of human malignancies, particularly
      colorectal cancer. A range of studies has been undertaken in breast cancer, with
      contradictory associations reported among beta-catenin expression,
      clinicopathologic variables, and disease outcome. We undertook an
      immunohistochemical study measuring the levels and subcellular localization of
      beta-catenin in 292 invasive ductal breast cancers with known treatment and
      outcome. No association with breast cancer-specific death was observed for
      cytoplasmic or membrane expression alone; however, a continuous score
      representing both locations (membrane minus cytoplasmic expression: MTC score)
      was associated with a worse outcome in univariate analysis (P = 0.004), and
      approached significance in a multivariate analysis model that included lymph
      node, progesterone receptor (PR), and HER2 status (P = 0.054). Therefore, the MTC
      score was used for further statistical analyses due to the importance of both the
      subcellular location and the levels of expression of beta-catenin. An association
      was identified between high cytoplasmic expression (low MTC score), and high
      tumor grade (P = 0.004), positive Ki67 (P = 0.005), negative estrogen receptor
      (ER) (P = 0.005), positive HER2 (P = 0.04) status, and an active phosphoinositide
      3-kinase pathway (P = 0.005), measured as PIK3CA mutations (P = 0.05) or PTEN
      loss (P = 0.05). Low cytoplasmic expression (high MTC score) was associated with
      the luminal A subtype (P = 0.004). In conclusion, a low beta-catenin MTC score is
      associated with an adverse outcome in breast cancer, which may be of mechanistic
      significance in the disease process.

PMID- 20056652
TI  - Lipid peroxidation and etheno DNA adducts in white blood cells of liver fluke
      infected patients: protection by plasma alpha-tocopherol and praziquantel.
AB  - Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk
      factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and
      lipid peroxidation-derived DNA damage, etheno (epsilon)-DNA adducts (epsilondA,
      epsilondC) in WBC and plasma alpha-tocopherol were measured in samples collected
      from O. viverrini-infected Thai patients (n = 50) and healthy noninfected
      volunteers (n = 20). epsilondA and epsilondC levels were three to five times
      higher (P < 0.001) in infected patients than in controls; O. viverrini infection
      also increased two to three times in the plasma inflammatory indicators, 8
      isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma alpha-tocopherol
      levels were two times lower in patients than in healthy controls (P < 0.001). Two
      months after a single dose to infected patients of the antiparasitic drug
      praziquantel, epsilondA and epsilondC levels in WBC were decreased to control
      level (P < 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and
      alkaline phosphatase (ALP) were concomitantly lowered. epsilondA and epsilondC
      levels in WBC were positively correlated with plasma 8-isoprostane,
      malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma
      alpha-tocopherol levels showed inverse correlations. We conclude that chronic
      O.viverrini infection induces an accumulation of lipid peroxidation-derived DNA
      damage through oxidative/nitrative stress, which is lowered by the plasma alpha
      tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine
      should be explored as a risk marker for opisthorchiasis-related
      cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic
      interventions.

PMID- 20056653
TI  - Interspecific gene flow in a multispecies oak hybrid zone in the Sierra
      Tarahumara of Mexico.
AB  - BACKGROUND AND AIMS: Interspecific gene flow can occur in many combinations among
      species within the genus Quercus, but simultaneous hybridization among more than
      two species has been rarely analysed. The present study addresses the genetic
      structure and morphological variation in a triple hybrid zone formed by Q.
      hypoleucoides, Q. scytophylla and Q. sideroxyla in north-western Mexico. METHODS:
      A total of 247 trees from ten reference and 13 presumed intermediate populations
      were characterized using leaf shape variation and geometric morphometrics, and
      seven nuclear microsatellites as genetic markers. Discriminant function analysis
      was performed for leaf shape variation, and estimates of genetic diversity and
      structure, and individual Bayesian genetic assignments were obtained. KEY
      RESULTS: Reference populations formed three completely distinct groups according
      to discriminant function analysis based on the morphological data, and showed
      low, but significant, genetic differentiation. Populations from the zone of
      contact contained individuals morphologically intermediate between pairs of
      species in different combinations, or even among the three species. The Bayesian
      admixture analysis found that three main genetic clusters best fitted the data,
      with good correspondence of reference populations of each species to one of the
      genetic clusters, but various degrees of admixture evidenced in populations from
      the contact area. CONCLUSIONS: The three oak species have formed a complex hybrid
      zone that is geographically structured as a mosaic, and comprising a wide range
      of genotypes, including hybrids between different species pairs, backcrosses and
      probable triple hybrids.

PMID- 20056654
TI  - On the detection and refinement of transcription factor binding sites using ChIP
      Seq data.
AB  - Coupling chromatin immunoprecipitation (ChIP) with recently developed massively
      parallel sequencing technologies has enabled genome-wide detection of protein-DNA
      interactions with unprecedented sensitivity and specificity. This new technology,
      ChIP-Seq, presents opportunities for in-depth analysis of transcription
      regulation. In this study, we explore the value of using ChIP-Seq data to better
      detect and refine transcription factor binding sites (TFBS). We introduce a novel
      computational algorithm named Hybrid Motif Sampler (HMS), specifically designed
      for TFBS motif discovery in ChIP-Seq data. We propose a Bayesian model that
      incorporates sequencing depth information to aid motif identification. Our model
      also allows intra-motif dependency to describe more accurately the underlying
      motif pattern. Our algorithm combines stochastic sampling and deterministic
      'greedy' search steps into a novel hybrid iterative scheme. This combination
      accelerates the computation process. Simulation studies demonstrate favorable
      performance of HMS compared to other existing methods. When applying HMS to real
      ChIP-Seq datasets, we find that (i) the accuracy of existing TFBS motif patterns
      can be significantly improved; and (ii) there is significant intra-motif
      dependency inside all the TFBS motifs we tested; modeling these dependencies
      further improves the accuracy of these TFBS motif patterns. These findings may
      offer new biological insights into the mechanisms of transcription factor
      regulation.

PMID- 20056655
TI  - The human telomeric protein hTRF1 induces telomere-specific nucleosome mobility.
AB  - Human telomeres consist of thousands of base pairs of double-stranded TTAGGG
      repeats, organized by histone proteins into tightly spaced nucleosomes. The
      double-stranded telomeric repeats are also specifically bound by the telomeric
      proteins hTRF1 and hTRF2, which are essential for telomere length maintenance and
      for chromosome protection. An unresolved question is what role nucleosomes play
      in telomere structure and dynamics and how they interact and/or compete with hTRF
      proteins. Here we show that hTRF1 specifically induces mobility of telomeric
      nucleosomes. Moreover, Atomic Force Microscopy (AFM) imaging shows that hTRF1
      induces compaction of telomeric DNA only in the presence of a nucleosome,
      suggesting that this compaction occurs through hTRF1-nucleosome interactions. Our
      findings reveal an unknown property of hTRF1 that has implications for
      understanding telomere structure and dynamics.

PMID- 20056656
TI  - Estimating the proportion of microarray probes expressed in an RNA sample.
AB  - A fundamental question in microarray analysis is the estimation of the number of
      expressed probes in different RNA samples. Negative control probes available in
      the latest microarray platforms, such as Illumina whole genome expression
      BeadChips, provide a unique opportunity to estimate the number of expressed
      probes without setting a threshold. A novel algorithm was proposed in this study
      to estimate the number of expressed probes in an RNA sample by utilizing these
      negative controls to measure background noise. The performance of the algorithm
      was demonstrated by comparing different generations of Illumina BeadChips,
      comparing the set of probes targeting well-characterized RefSeq NM transcripts
      with other probes on the array and comparing pure samples with heterogenous
      samples. Furthermore, hematopoietic stem cells were found to have a larger
      transcriptome than progenitor cells. Aire knockout medullary thymic epithelial
      cells were shown to have significantly less expressed probes than matched wild
      type cells.

PMID- 20056657
TI  - Analysis of the impact of a uracil DNA glycosylase attenuated in AP-DNA binding
      in maintenance of the genomic integrity in Escherichia coli.
AB  - Uracil DNA glycosylase (Ung) initiates the uracil excision repair pathway. We
      have earlier characterized the Y66W and Y66H mutants of Ung and shown that they
      are compromised by approximately 7- and approximately 170-fold, respectively in
      their uracil excision activities. In this study, fluorescence anisotropy
      measurements show that compared with the wild-type, the Y66W protein is
      moderately compromised and attenuated in binding to AP-DNA. Allelic exchange of
      ung in Escherichia coli with ung::kan, ungY66H:amp or ungY66W:amp alleles showed
      approximately 5-, approximately 3.0- and approximately 2.0-fold, respectively
      increase in mutation frequencies. Analysis of mutations in the rifampicin
      resistance determining region of rpoB revealed that the Y66W allele resulted in
      an increase in A to G (or T to C) mutations. However, the increase in A to G
      mutations was mitigated upon expression of wild-type Ung from a plasmid borne
      gene. Biochemical and computational analyses showed that the Y66W mutant
      maintains strict specificity for uracil excision from DNA. Interestingly, a
      strain deficient in AP-endonucleases also showed an increase in A to G mutations.
      We discuss these findings in the context of a proposal that the residency of DNA
      glycosylase(s) onto the AP-sites they generate shields them until recruitment of
      AP-endonucleases for further repair.

PMID- 20056658
TI  - Experimental validation of left ventricular transmural strain gradient with
      echocardiographic two-dimensional speckle tracking imaging.
AB  - AIMS: To validate intramural strain measured by a speckle tracking imaging (STI)
      system against that measured by sonomicrometry crystals. METHODS AND RESULTS: In
      11 anaesthetized sheep, six sets of three sonomicrometry crystals were implanted
      in endo-, mid-wall, and epimyocardium on the anterior and lateral walls.
      Circumferential strain (CS) was calculated at three layers from endo-, mid-wall,
      and epicardial speckle. Radial strain (RS) was assessed for inner and outer
      halves of the myocardium. We compared ultrasound-derived strain measurements
      against those by sonomicrometry at baseline and during pharmacological stress and
      coronary occlusion. Intraclass correlation coefficients at baseline and during
      coronary occlusion were as follows: endocardial CS 0.80, 0.97; mid-wall CS 0.58,
      0.89; epicardial CS 0.71, 0.81; endocardial RS 0.50, 0.78; epicardial RS 0.35,
      0.83; and total RS 0.33, 0.71; respectively. At baseline, endocardial strains
      were higher than mid-wall and epicardial strains, resulting in an inner/outer
      wall RS gradient and inner/mid/outer wall CS gradients. Ischaemia caused
      significant reduction in all strains and disappearance of the strain gradient.
      CONCLUSION: A newly developed STI system can accurately assess the intramural
      heterogeneity of CS distribution in normal and ischaemic myocardial segments and
      has the potential to become a non-invasive bedside tool for characterizing
      myocardial strain gradient.

PMID- 20056660
TI  - How does it feel to work as a doctor in the NHS?

PMID- 20056661
TI  - The struggle against sins.

PMID- 20056662
TI  - Female editorship is an important indicator of gender imbalance.

PMID- 20056663
TI  - Medical electives: a chance for international health.

PMID- 20056664
TI  - Why tomorrow's doctors need primary care today.

PMID- 20056665
TI  - Who evaluates public health programmes? A review of the NHS Breast Screening
      Programme.

PMID- 20056666
TI  - Career destinations, views and future plans of the UK medical qualifiers of 1988.
AB  - OBJECTIVES: To report the career destinations, views and future plans of a cohort
      of senior doctors who qualified in the 1980s. METHODS: Postal questionnaire
      survey of all doctors who qualified from all UK medical schools in 1988. RESULTS:
      The response rate was 69%. We estimated that 81% of the total cohort was working
      in the NHS, 16 years after qualification; and that at least 94% of graduates who,
      when students, were from UK homes, were working in medicine. Of NHS doctors, 30%
      worked part-time. NHS doctors rated their job satisfaction highly (median score
      19.9, scale 5-25) but were less satisfied with the amount of leisure time
      available to them (median score 5.4, scale 1-10). NHS doctors were very positive
      about their careers, but were less positive about working hours and some other
      aspects of the NHS. Women were more positive than men about working conditions;
      general practitioners were more positive than hospital doctors. Twenty-five
      percent reported unmet needs for further training or career-related advice,
      particularly about career development. Twenty-nine percent intended to reduce
      their hours in future, while 6%, mainly part-time women, planned to increase
      their hours. Overall, 10% of NHS doctors planned to do more service work in
      future and 24% planned to do less; among part-time women, 18% planned to do more
      and only 14% less. CONCLUSIONS: These NHS doctors, now in their 40s, had a high
      level of satisfaction with their jobs and their careers but were less satisfied
      with some other aspects of their working environment. A substantial percentage
      had expectations about future career development and change.

PMID- 20056667
TI  - A unilateral whiteout: when not to insert a chest drain.

PMID- 20056668
TI  - Comparative evaluation of homeopathy and allopathy within the Parisian hospital
      system, 1849-1851.

PMID- 20056669
TI  - Live and laugh: a journey through motor neurone disease.

PMID- 20056670
TI  - Effect of prostaglandin F2 alpha on local luteotropic and angiogenic factors
      during induced functional luteolysis in the bovine corpus luteum.
AB  - The essential role of endometrial prostaglandin F2 alpha (PTGF) for induction of
      the corpus luteum (CL) regression is well documented in the cow. However, the
      acute effects of PTGF on known local luteotropic factors (oxytocin [OXT] and its
      receptor, insulin-like growth factor [IGF] 1, and progesterone and its receptor),
      the principal angiogenic factor vascular endothelial growth factor (VEGF) A and
      the capillary destabilization factor angiopoietin (ANGPT) 2 were not thoroughly
      studied in detail. The aim of this study was therefore to evaluate the tissue
      concentration of these factors during PTGF induced luteolysis. In addition the
      mRNA expression of progesterone receptor (PGR), OXT receptor (OXTR), IGF1,
      IGFBP1, ANGPT1, and ANGPT2 was determined at different times after PTGF
      treatment. Cows (n = 5 per group) in the mid-luteal phase (Days 8-12, control
      group) were injected with the PTGF analog (cloprostenol), and CL were collected
      by transvaginal ovariectomy at 0.5, 2, 4, 12, 24, 48, and 64 h after injection.
      The mRNA expression was analyzed by quantitative real-time PCR, and the protein
      concentration was evaluated by enzyme immunoassay or radioimmunoassay.
      Progesterone concentrations, as well as mRNA expression of PGR, in CL tissue were
      significantly down-regulated by 12 h after PTGF. Tissue OXT peptide and OXTR mRNA
      decreased significantly after 2 h, followed by a continuous decrease of OXT mRNA.
      IGF1 and VEGFA protein already decreased after 0.5 h. By contrast, the IGFBP1
      mRNA was up-regulated significantly after 2 h to a high plateau. ANGPT2 protein
      and mRNA significantly increased during the first 2 h, followed by a steep
      decrease after 4 h. The acute decrease of local luteotropic activity and acute
      changes of ANGPT2 and VEGFA suggest that modulation of vascular stability may be
      a key component in the cascade of events leading to functional luteolysis.

PMID- 20056671
TI  - Ablation of Indian hedgehog in the murine uterus results in decreased cell cycle
      progression, aberrant epidermal growth factor signaling, and increased estrogen
      signaling.
AB  - Conditional ablation of Indian hedgehog (Ihh) in the murine uterus results in
      mice that are sterile because of defects in embryo implantation. We performed
      microarray analysis on these mice at the time point at which the Ihh target genes
      are induced by the administration of exogenous hormone to mimic Day 3.5 of
      pregnancy. This analysis identified 863 genes altered by the conditional ablation
      of Ihh. Of these, genes that regulated the cell cycle were overrepresented. In
      addition, genes involved in epidermal growth factor (EGF) and estrogen (E2)
      signaling were found to be deregulated upon Ihh ablation. Furthermore, upon
      conditional ablation of Ihh, 15-mo-old mice exhibited hallmarks of estrogenized
      uteri, such as cystically dilated glands and hyalinized stroma. Thus, Ihh
      regulates embryo implantation by having an impact on the cell cycle, EGF
      signaling, and E2 signaling.

PMID- 20056672
TI  - Short photoperiod initiated during adulthood sustains reproductive function in
      older female siberian hamsters more effectively than short photoperiod initiated
      before puberty.
AB  - Reproductive aging in female mammals is characterized by a progressive decline in
      fertility and fecundity. Many women delay their first full-term pregnancy until
      an age at which their reproductive potential has already declined. No treatment
      is presently available to delay the aging process. In a limited number of rodent
      species, caloric restriction sustained reproductive function in older females,
      and in most investigations, sexual maturation was delayed because caloric
      restriction was initiated at weaning. We have previously reported similar
      outcomes in female Siberian hamsters that were reared in short photoperiod (SP),
      which profoundly inhibits reproductive physiology. When compared to hamsters held
      in long photoperiod (LP), females reared in SP matured much later and had greater
      reproductive success at 9 mo of age. Herein, we determined if delayed onset of
      sexual maturation was necessary for SP to decelerate reproductive aging. We
      initiated a 6-mo period of SP before or after sexual maturation and measured the
      reproductive success of females at 12 mo of age. Maintenance of hamsters in SP
      beginning after puberty was associated with significantly greater litter success
      (77%) compared to imposition of SP before puberty (35%); the difference in
      weaning success was even greater (73% and 12%, respectively). Regardless of which
      SP regime was used, litter success of females exposed to SP was substantially
      greater than that of 12-mo-old females held continuously in LP (6%). The efficacy
      of SP in decelerating female reproductive aging is manifest at several life
      stages and is greater when treatment is initiated after rather than before
      puberty.

PMID- 20056673
TI  - Overweight and obesity in infertility: cost and consequences.

PMID- 20056674
TI  - Economic consequences of overweight and obesity in infertility: a framework for
      evaluating the costs and outcomes of fertility care.
AB  - BACKGROUND: Overweight and obesity are an epidemic in Western society, and have a
      strong impact on fertility. We studied the consequences of overweight and obesity
      with respect to fecundity, costs of fertility treatment and pregnancy outcome in
      subfertile women. METHODS: We searched the literature for systematic reviews and
      large studies reporting on the effect of weight on both fecundity and pregnancy
      outcome in subfertile women. We collected data on costs of treatment with
      ovulation induction, intrauterine insemination and in vitro fertilization, as
      well as costs of pregnancy complications. We calculated, for ovulatory and
      anovulatory women separately, the number of expected pregnancies, complications
      and costs in a hypothetical cohort of 1000 normal weight, overweight and obese
      women each. RESULTS: In our hypothetical cohort of 1000 women, compared with
      women with normal weight, live birth was decreased by 14 and 15% (from 806 live
      births to 692 and 687 live births) in overweight and obese anovulatory women,
      respectively, for ovulatory women it was decreased by 22 and 24% (from 698 live
      births to 546 and 531 live births), respectively. These outcomes were associated
      with an increase in the number of complications and associated costs leading to
      cost per live birth in anovulatory overweight and obese women were 54 and 100%
      higher than their normal weight counterparts, for ovulatory women they were 44
      and 70% higher, respectively. CONCLUSIONS: Overweight and obese subfertile women
      have a reduced probability of successful fertility treatment and their
      pregnancies are associated with more complications and higher costs.

PMID- 20056675
TI  - Survivin and Smac gene expressions but not livin are predictors of prognosis in
      non-small cell lung cancer patients treated with adjuvant chemotherapy following
      surgery.
AB  - OBJECTIVE: Survivin and livin, which are members of the inhibitor of apoptosis
      protein family, regulate both programmed cell death and proliferation. Second
      mitochondria-derived activator of caspase is thought to regulate apoptosis by
      antagonizing inhibitor of apoptosis protein. These gene expressions are regarded
      as prognostic markers in some malignancies. However, result in previous studies
      of the association of these gene expressions with prognosis of patients with non
      small cell lung cancer remains contradictory. METHODS: Survivin, livin and second
      mitochondria-derived activator of caspase mRNA was detected by semi-quantitative
      reverse transcriptase-polymerase chain reaction in surgical resected tumor
      specimen from 66 non-small cell lung patients who received adjuvant platinum
      based chemotherapy. RESULTS: Results showed that patients with survivin high
      expression had significantly shorter tumor-free survival (P = 0.012) and overall
      survival (P = 0.007) than those with survivin low expression. There was a
      significant association of second mitochondria-derived activator of caspase high
      expression in non-small cell lung cancer tissue with longer tumor-free survival
      (P = 0.021) and overall survival (P = 0.0013). However, livin mRNA expression
      level had no impact on the tumor-free survival and overall survival of the
      patients. In multivariate analyses, survivin mRNA high expression (P = 0.033 and
      P = 0.024) and advanced pathologic stage (P = 0.009 and P = 0.008) were the
      factors which independently predicted a worse tumor-free survival and overall
      survival. CONCLUSIONS: Our data suggest that assessment of survivin and second
      mitochondria-derived activator of caspase mRNA expression may be useful for
      predicting survival in non-small cell lung cancer patients receiving platinum
      based chemotherapy after surgical resection and can provide valuable information
      for deciding better therapy strategy.

PMID- 20056677
TI  - Extrachromosomal amplification mechanisms in a glioma with amplified sequences
      from multiple chromosome loci.
AB  - Accumulation of extrachromosomal DNA molecules (double minute) is often
      responsible for gene amplification in cancers, but the mechanisms leading to
      their formation are still largely unknown. By using quantitative PCR, chromosome
      walking, in situ hybridization on metaphase chromosomes and whole genome
      analysis, we studied a glioma containing four extrachromosomally amplified loci
      (7p11, 1q32.1, 5p15 and 9p2). Complex extrachromosomal DNA molecules were formed
      by the fusion of several syntenic or non-syntenic DNA fragments from 7p11, 5p15
      to 9p2. Fragments ranged from a few base pairs to megabase pairs. Scars of the
      amplification process remained at the original locus in the form of deletions or
      chromosome rearrangements. Chromosome fragmentation, due to replication stress,
      could explain this complex situation. In contrast, at 1q32.1, the initial
      extrachromosomal DNA molecule resulted from the circularization of a single
      fragment associated with an intrachromosomal deletion including, but larger than,
      the amplified sequence. The nature of the sequences involved in these
      rearrangements suggests that a V(D)J-like illegitimate recombination contributes
      to its formation.

PMID- 20056676
TI  - Col4a1 mutation in mice causes defects in vascular function and low blood
      pressure associated with reduced red blood cell volume.
AB  - Collagen type IV is the major structural component of the basement membrane and
      COL4A1 mutations cause adult small vessel disease, familial porencephaly and
      hereditary angiopathy with nephropathy aneurysm and cramps (HANAC) syndrome.
      Here, we show that animals with a Col4a1 missense mutation (Col4a1(+/Raw))
      display focal detachment of the endothelium from the media and age-dependent
      defects in vascular function including a reduced response to nor-epinephrine. Age
      dependent hypersensitivity to acetylcholine is abolished by inhibition of nitric
      oxide synthase (NOS) activity, indicating that Col4a1 mutations affect
      vasorelaxation mediated by endothelium-derived nitric oxide (NO). These defects
      are associated with a reduction in basal NOS activity and the development of
      heightened NO sensitivity of the smooth muscle. The vascular function defects are
      physiologically relevant as they maintain in part the hypotension in mutant
      animals, which is primarily associated with a reduced red blood cell volume due
      to a reduction in red blood cell number, rather than defects in kidney function.
      To understand the molecular mechanism underlying these vascular defects, we
      examined the deposition of collagen type IV in the basement membrane, and found
      it to be defective. Interestingly, this mutation also leads to activation of the
      unfolded protein response. In summary, our results indicate that mutations in
      COL4A1 result in a complex vascular phenotype encompassing defects in maintenance
      of vascular tone, endothelial cell function and blood pressure regulation.

PMID- 20056678
TI  - Regional specification of stomatal production by the putative ligand CHALLAH.
AB  - The problem of modulating cell fate programs to create distinct patterns and
      distributions of specialized cell types in different tissues is common to complex
      multicellular organisms. Here, we describe the previously uncharacterized CHALLAH
      (CHAL) gene, which acts as a tissue-specific regulator of epidermal pattern in
      Arabidopsis thaliana. Arabidopsis plants produce stomata, the cellular valves
      required for gas exchange, in virtually all aerial organs, but stomatal density
      and distribution differ among organs and along organ axes. Such regional
      regulation is particularly evident in plants mutant for the putative receptor TOO
      MANY MOUTHS (TMM), which produce excess stomata in leaves but no stomata in
      stems. Mutations in CHAL suppress tmm phenotypes in a tissue-specific manner,
      restoring stomatal production in stems while minimally affecting leaves. CHAL is
      similar in sequence to the putative stomatal ligands EPF1 and EPF2 and, like the
      EPFs, can reduce or eliminate stomatal production when overexpressed. However,
      CHAL and the EPFs have different relationships to TMM and the ERECTA (ER) family
      receptors. We propose a model in which CHAL and the EPFs both act through ER
      family receptors to repress stomatal production, but are subject to opposite
      regulation by TMM. The existence of two such ligand classes provides an
      explanation for TMM dual functionality and tissue-specific phenotypes.

PMID- 20056679
TI  - Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control
      gastrulation movements in parallel to the Wnt/PCP pathway.
AB  - The vertebrate body plan is established in two major steps. First, mesendoderm
      induction singles out prospective endoderm, mesoderm and ectoderm progenitors.
      Second, these progenitors are spatially rearranged during gastrulation through
      numerous and complex movements to give rise to an embryo comprising three
      concentric germ layers, polarised along dorsoventral, anteroposterior and left
      right axes. Although much is known about the molecular mechanisms of mesendoderm
      induction, signals controlling gastrulation movements are only starting to be
      revealed. In vertebrates, Nodal signalling is required to induce the mesendoderm,
      which has precluded an analysis of its potential role during the later process of
      gastrulation. Using time-dependent inhibition, we show that in Xenopus, Nodal
      signalling plays sequential roles in mesendoderm induction and gastrulation
      movements. Nodal activity is necessary for convergent extension in axial mesoderm
      and for head mesoderm migration. Using morpholino-mediated knockdown, we found
      that the Nodal ligands Xnr5 and Xnr6 are together required for mesendoderm
      induction, whereas Xnr1 and Xnr2 act later to control gastrulation movements.
      This control is operated via the direct regulation of key movement-effector
      genes, such as papc, has2 and pdgfralpha. Interestingly, however, Nodal does not
      appear to mobilise the Wnt/PCP pathway, which is known to control cell and tissue
      polarity. This study opens the way to the analysis of the genetic programme and
      cell behaviours that are controlled by Nodal signalling during vertebrate
      gastrulation. It also provides a good example of the sub-functionalisation that
      results from the expansion of gene families in evolution.

PMID- 20056680
TI  - Nectin-like molecules/SynCAMs are required for post-crossing commissural axon
      guidance.
AB  - The Necl/SynCAM subgroup of immunoglobulin superfamily cell adhesion molecules
      has been implicated in late stages of neural circuit formation. They were shown
      to be sufficient for synaptogenesis by their trans-synaptic interactions.
      Additionally, they are involved in myelination, both in the central and the
      peripheral nervous system, by mediating adhesion between glia cells and axons.
      Here, we show that Necls/SynCAMs are also required for early stages of neural
      circuit formation. We demonstrate a role for Necls/SynCAMs in post-crossing
      commissural axon guidance in the developing spinal cord in vivo. Necl3/SynCAM2,
      the family member that has not been characterized functionally so far, plays a
      crucial role in this process. It is expressed by floorplate cells and interacts
      with Necls/SynCAMs expressed by commissural axons to mediate a turning response
      in post-crossing commissural axons.

PMID- 20056681
TI  - Multi-step control of muscle diversity by Hox proteins in the Drosophila embryo.
AB  - Hox transcription factors control many aspects of animal morphogenetic diversity.
      The segmental pattern of Drosophila larval muscles shows stereotyped variations
      along the anteroposterior body axis. Each muscle is seeded by a founder cell and
      the properties specific to each muscle reflect the expression by each founder
      cell of a specific combination of 'identity' transcription factors. Founder cells
      originate from asymmetric division of progenitor cells specified at fixed
      positions. Using the dorsal DA3 muscle lineage as a paradigm, we show here that
      Hox proteins play a decisive role in establishing the pattern of Drosophila
      muscles by controlling the expression of identity transcription factors, such as
      Nautilus and Collier (Col), at the progenitor stage. High-resolution analysis,
      using newly designed intron-containing reporter genes to detect primary
      transcripts, shows that the progenitor stage is the key step at which segment
      specific information carried by Hox proteins is superimposed on intrasegmental
      positional information. Differential control of col transcription by the
      Antennapedia and Ultrabithorax/Abdominal-A paralogs is mediated by separate cis
      regulatory modules (CRMs). Hox proteins also control the segment-specific number
      of myoblasts allocated to the DA3 muscle. We conclude that Hox proteins both
      regulate and contribute to the combinatorial code of transcription factors that
      specify muscle identity and act at several steps during the muscle-specification
      process to generate muscle diversity.

PMID- 20056682
TI  - Mitochondrial divergence between 2 populations of the hooded capuchin, Cebus
      (Sapajus) cay (Platyrrhini, Primates).
AB  - We analyzed the molecular divergence of 2 separate populations of Cebus apella
      paraguayanus, recently considered a junior synonym of Cebus cay, and estimated
      its time of separation from C. apella. Cytochrome b DNA from 23 C. cay from
      Brazil and 9 from Paraguay showed 24 haplotypes (20 and 4, respectively),
      accounting for 29 variable sites (19 transitions and 10 transversions), with
      40.0%, 26.7%, and 33.0% replacements at first, second, and third codon positions,
      respectively. Genetic distance between haplotypes averaged 0.5%, with 1.1%
      between C. cay populations. Phylogenetic reconstructions and median joining
      separated C. cay from Brazil and Paraguay. Neighbor joining showed C. cay and C.
      apella as sister groups, although C. cay and C. apella collapsed in maximum
      parsimony and maximum likelihood topologies. Analysis of molecular variance
      showed the highest variance component between C. cay populations, and mismatch
      distribution indicated that this species suffered a recent demographic expansion.
      Divergence time estimates suggested that the 2 populations of C. cay split in the
      Pleistocene, a period of repeated glaciation events leading to drastic changes in
      the vegetation composition of different biomes.

PMID- 20056683
TI  - Possible molecular mechanisms underlying age-related cardiomyocyte apoptosis in
      the F344XBN rat heart.
AB  - Despite advances in treatment, age-related cardiac dysfunction still remains a
      leading cause of cardiovascular death. Recent data have suggested that increases
      in cardiomyocyte apoptosis may be involved in the pathological remodeling of
      heart. Here, we examine the effects of aging on cardiomyocyte apoptosis in 6-, 30
      , and 36-month-old Fischer344 x Brown Norway F1 hybrid rats (F344XBN). Compared
      with 6-month hearts, aged hearts exhibited increased TdT-mediated dUTP nick end
      labeling-positive nuclei, caspase-3 activation, caspase-dependent cleavage of
      alpha-fodrin and diminished phosphorylation of protein kinase B/Akt (Thr 308).
      These age-dependent increases in cardiomyocyte apoptosis were associated with
      alterations in the composition of the cardiac dystrophin glycoprotein complex and
      elevated cytoplasmic IgG and albumin immunoreactivity. Immunohistochemical
      analysis confirmed these data and demonstrated qualitative differences in
      localization of dystrophin-glycoprotein complex (DGC) molecules with aging. Taken
      together, these data suggest that aging-related increases in cardiac apoptotic
      activity model may be due, at least in part, to age-associated changes in DGC
      structure.

PMID- 20056684
TI  - The moderating influence of demographic characteristics, social support, and
      religious coping on the effectiveness of a multicomponent psychosocial caregiver
      intervention in three racial ethnic groups.
AB  - This article extends the findings from the Resources for Enhancing Alzheimer's
      Caregiver Health (REACH II) program, a multisite randomized clinical trial of a
      multicomponent psychosocial intervention, to improve the well-being of informal
      caregivers (CGs) of persons with dementia. We used residual change scores and
      stepwise hierarchical regression analyses to explore separately in 3 racial
      ethnic groups (Hispanic or Latino, Black or African American, and White or
      Caucasian) how the effects of the intervention were moderated by CG
      characteristics (sex, age, education, and relationship), CG resources (social
      support), and religious coping. The results indicated that CG's age and religious
      coping moderated the effects of the intervention for Hispanics and Blacks. The
      older Hispanic and Black CGs who received the intervention reported a decrease in
      CG burden from baseline to follow-up. Black CGs with less religious coping who
      received the intervention also reported a decrease in depressive symptoms from
      baseline to follow-up.

PMID- 20056685
TI  - The role of expressed emotion in relationships between psychiatric staff and
      people with a diagnosis of psychosis: a review of the literature.
AB  - The concept of expressed emotion (EE) has been extended to the study of staff
      patient relationships in schizophrenia. A comprehensive review of the literature
      identified a total of 27 studies investigating EE in this group published between
      1990 and 2008. The article aims to assess whether the concept of EE is a useful
      and valid measure of the quality of professional caregiver and patient
      relationships, given that staff may be less emotionally invested in relationships
      than relatives. In doing so, it summarizes methods of measuring EE, the nature of
      professional EE compared with familial EE, associations between high EE and
      patient outcomes, associations between EE and both patient and staff variables,
      and intervention studies to reduce staff high EE. The available evidence suggests
      that the Camberwell Family Interview is an acceptable measure of EE in staff
      patient relationships, although the Five Minute Speech Sample may provide a less
      resource intensive alternative. However, in contrast to familial research,
      neither the EE status on the Camberwell Family Interview nor the Five Minute
      Speech Sample show a robust relationship with outcomes. The presence or absence
      of a positive staff-patient relationship may have more predictive validity in
      this group. There is relatively consistent evidence of associations between staff
      criticism and poorer patient social functioning. Consistent with findings in
      familial research, staff attributions may play a key role in driving critical
      responses, and it may be possible to reduce staff high EE by modifying negative
      appraisals.

PMID- 20056686
TI  - Pharmacokinetics of two generic co-formulations of lopinavir/ritonavir for HIV
      infected children: a pilot study of paediatric Lopimune versus the branded
      product in healthy adult volunteers.
AB  - OBJECTIVES: To determine the pharmacokinetic profiles of lopinavir and ritonavir
      in two newly developed generic co-formulations for HIV-infected children
      (Lopimune paediatric tablets and granules, 100/25 mg of lopinavir/ritonavir,
      Cipla Pharmaceuticals), and to compare these with the branded product (Kaletra).
      METHODS: This Phase I, comparative, open-label, three-period, single-dose,
      crossover study was designed as a pilot study to exclude large (>40%) differences
      in the exposure to lopinavir. Single doses of medication, normalized to 400 mg of
      lopinavir, were administered on an empty stomach, 1 week apart. A 32 h
      pharmacokinetic curve was recorded. In an additional part of the study, in five
      of the same volunteers, a pharmacokinetic curve was recorded after administration
      of the Lopimune granules and Kaletra oral solution, both with food. RESULTS:
      Twelve healthy subjects were enrolled (four females). The median (range) age,
      height and body weight were 24 (21-55) years, 1.79 (1.63-1.95) m and 72 (51-87)
      kg, respectively. The median [interquartile range (IQR)] AUC(0-t) of lopinavir
      was 71.8 (48.8-93.5), 38.7 (28.7-52.2) and 58.7 (42.5-79.4) mg.h/L with Kaletra
      tablets, Lopimune granules and Lopimune paediatric tablets, all taken on an empty
      stomach, respectively. The respective C(max) values were 7.2 (5.8-8.3), 4.6 (4.1
      5.2) and 6.5 (5.0-7.1) mg/L after intake of the different formulations. When
      comparing the Lopimune formulations with the reference product Kaletra, for all
      parameters the differences were statistically significant (P <or= 0.015).
      Ritonavir exposure was also lower after intake of the generic formulations versus
      Kaletra. When the five subjects took the Lopimune granules or Kaletra solution
      with food, the median (IQR) AUC(0-t) of lopinavir was 58.5 (55.4-77.6) and 49.6
      (39.1-58.1) mg.h/L, respectively. CONCLUSIONS: Large differences in
      pharmacokinetic parameters can be excluded for Lopimune paediatric tablets when
      compared with the branded product and taken on an empty stomach, and also for
      Lopimune granules when these are taken with food.

PMID- 20056687
TI  - Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir.
AB  - OBJECTIVES: To understand the dynamic viral evolution observed during failure on
      raltegravir-containing regimens, we studied the genotypic and phenotypic patterns
      of resistance to raltegravir and the residual replication capacity (rRC) of HIV-1
      variants selected in vivo. METHODS: Clonal genotypic analyses were performed on
      sequential HIV-1 integrase sequences amplified from 11 failing patients and
      sampled every 4-24 weeks for up to 64 weeks. Fully replicating recombinant
      viruses were generated using modified vectors in which selected viral integrase
      genes amplified from patients' plasma were cloned. rRC was measured by a novel
      multiple cycle competition assay. Resistance to raltegravir and the rRC of
      resistant HIV-1 variants selected in vivo were evaluated in purified CD4+ T
      cells. RESULTS: In all of the patients but one, failure was associated with
      selection of mutations in positions 143, 148 or 155. Unlike mutations at position
      143 (Y143S/K/R), identified alone or in combination with others, mutations at
      position 148 and 155 were always found in combination. A wide range of resistance
      levels to raltegravir [from 10- to 770-fold change in 50% inhibitory
      concentration (IC(50)) compared with baseline] was observed using recombinant
      viral clones. Finally, rRC was not significantly altered in highly resistant
      variants. DISCUSSION: Two patterns of viral evolution were observed in the
      resistant viral populations, driving the variants towards a fast (most of them
      with G140S + Q148H mutations) or progressive increase in resistance to
      raltegravir. These results may have implications either for the evaluation of
      genotypic results, or for the correct clinical use of the compound.

PMID- 20056688
TI  - Characterization of clinical Escherichia coli isolates from China containing
      transferable quinolone resistance determinants.
AB  - BACKGROUND: The categories of recognized transferable quinolone resistance
      determinants have been increasing sharply. The rapid horizontal transfer of these
      quinolone resistance genes has caused concern since they bring new dissemination
      possibilities for quinolone resistance. METHODS: In total, 579 clinical
      Escherichia coli isolates were subjected to antimicrobial susceptibility testing,
      screening for qnr alleles, qepA and aac-(6')-Ib-cr by PCR amplification and DNA
      sequence analysis. Isolates containing transferable quinolone resistance
      determinants were further characterized by mutation analysis in the quinolone
      resistance determining regions (QRDRs) of GyrA and ParC, phylogenetic typing and
      PFGE to determine their genetic relatedness. RESULTS: After PCR screening and
      sequence analysis, transferable quinolone resistance determinants were identified
      in 74 of 579 E. coli isolates (12.8%). The antimicrobial resistance profiles and
      phylogenetic groups differed between isolates containing different categories of
      transferable quinolone resistance determinant. Most of the isolates containing
      qepA alone were highly resistant to ciprofloxacin (MIC >or= 512 mg/L) and
      belonged to phylogenetic group D (22/25), while most of the isolates containing
      aac-(6')-Ib-cr alone belonged to phylogenetic group A (17/35) or D (16/35). Of 74
      E. coli isolates containing transferable quinolone resistance determinants, 69
      PFGE patterns and 19 clusters were identified. CONCLUSIONS: The great genetic
      variation of E. coli hosts containing transferable quinolone resistance
      determinants demonstrated the high transmission capacity of these mechanisms. It
      is urgent to characterize and block their transmission routes in order that the
      utility of quinolones is preserved.

PMID- 20056689
TI  - Environmental tobacco use and indicators of metabolic syndrome in Chinese adults.
AB  - INTRODUCTION: Exposure to environmental tobacco smoke (ETS) is a widespread
      source of nicotine exposure, and an estimated 540 million Chinese are exposed to
      ETS in mainland China. We aimed to investigate associations of ETS exposure and
      metabolic syndrome (MetS) as well as its individual components independent of
      active smoking status in Chinese adults. METHODS: A cross-sectional data of 304
      randomly selected Chinese households with fourth (elementary school) and seventh
      (middle school) graders in Qingdao city was used. Assessments of fat mass,
      metabolic biomarkers, personal history of illness, and health behaviors were
      conducted. RESULTS: Proportions of current smokers were 3% in women and 60.5% in
      men, and more men reported exposure to ETS 5-7 days per week than women (60.8%
      vs. 48.1%). Exposure to ETS was significantly associated with enhanced risks of
      MetS (odds ratio [OR] = 2.8, p = .01), hypertriglyceridemia (OR = 2.1, p = .02),
      and central obesity (OR = 2.7, p < .001) and reduced levels of high-density
      lipoprotein cholesterol (OR = 1.9, p = .02) and elevated mean levels of fasting
      insulin (p < .01). These observed associations were independent of active smoking
      status and were successfully replicated in female never-smokers. CONCLUSIONS:
      Results of our study support the hypothesis that ETS exposure is independently
      associated with MetS and its individual components. Further large-scale studies
      with longitudinal design and objective assessment of ETS exposure are needed to
      elucidate the underlying mechanisms and the causal effects of passive smoking on
      MetS. Findings of this work emphasize the importance of developing community
      intervention to reduce smoking, ETS, and promote healthy lifestyle.

PMID- 20056690
TI  - Homoplasy and distribution of AFLP fragments: an analysis in silico of the genome
      of different species.
AB  - We carried out an in silico analysis of the complete genome sequences of 14
      species, including eukaryotes, prokaryotes, and archaea, to investigate the
      proportion of amplified fragment length polymorphism bands that are homoplasious
      for the different species, as well as the distribution of fragment lengths. We
      investigated several possible reasons for the disagreement, previously observed
      in Arabidopsis thaliana, between the observed fragment length distribution and
      the null random sequence distribution, which occurs in the direction of a deficit
      of fragments of small length and an excess of those of large length with respect
      to the null distribution. We made the following findings: 1) The positive
      relationship previously found between the percentage of homoplasy and genome size
      is a direct consequence of the number of observed bands and the GC content. For
      the same number of observed bands, the percentage of homoplasy is independent of
      the genome size of the species. 2) The disagreement between the observed fragment
      length distribution and the null random sequence distribution observed in A.
      thaliana is a phenomenon that also occurs in other species. 3) This disagreement
      is due neither to the structure of the genomes in isochores nor the possible
      impact of indels in reducing the number of restriction sites, two hypotheses
      discussed in the literature. 4) Nor is the disagreement eliminated by using
      restriction enzymes with balanced motifs. 5) The discrepancy seems to be caused,
      rather, by the nonrandom distribution of restriction enzyme motifs.

PMID- 20056691
TI  - Field, genetic, and modeling approaches show strong positive selection acting
      upon an insecticide resistance mutation in Anopheles gambiae s.s.
AB  - Alleles subject to strong, recent positive selection will be swept toward
      fixation together with contiguous sections of the genome. Whether the genomic
      signatures of such selection will be readily detectable in outbred wild
      populations is unclear. In this study, we employ haplotype diversity analysis to
      examine evidence for selective sweeps around knockdown resistance (kdr) mutations
      associated with resistance to dichlorodiphenyltrichloroethane and pyrethroid
      insecticides in the mosquito Anopheles gambiae. Both kdr mutations have
      significantly lower haplotype diversity than the wild-type (nonresistant) allele,
      with kdr L1014F showing the most pronounced footprint of selection. We complement
      these data with a time series of collections showing that the L1014F allele has
      increased in frequency from 0.05 to 0.54 in 5 years, consistent with a maximum
      likelihood-fitted selection coefficient of 0.16 and a dominance coefficient of
      0.25. Our data show that strong, recent positive selective events, such as those
      caused by insecticide resistance, can be identified in wild insect populations.

PMID- 20056692
TI  - Person-centered care for nursing home residents: the culture-change movement.
AB  - The "culture change" movement represents a fundamental shift in thinking about
      nursing homes. Facilities are viewed not as health care institutions, but as
      person-centered homes offering long-term care services. Culture-change principles
      and practices have been shaped by shared concerns among consumers, policy makers,
      and providers regarding the value and quality of care offered in traditional
      nursing homes. They have shown promise in improving quality of life as well as
      quality of care, while alleviating such problems as high staff turnover. Policy
      makers can encourage culture change and capitalize on its transformational power
      through regulation, reimbursement, public reporting, and other mechanisms.

PMID- 20056693
TI  - Spinal cord injury.

PMID- 20056694
TI  - Topical intranasal corticosteroids for otitis media with effusion in primary
      care.

PMID- 20056696
TI  - Bit of an animal.

PMID- 20056698
TI  - China is accused of "warehousing" and denying treatment to its illicit drug
      users.

PMID- 20056699
TI  - The transcriptional regulators RamA and RamB are involved in the regulation of
      glycogen synthesis in Corynebacterium glutamicum.
AB  - When grown in glucose-, fructose- or sucrose-containing medium, the amino acid
      producer Corynebacterium glutamicum transiently accumulates large amounts of
      glycogen (up to 10% of its dry weight), whereas only a marginal amount of
      glycogen is formed during growth with acetate. This carbon-source-dependent
      regulation is at least partially due to transcriptional control of glgC, encoding
      ADP-glucose pyrophosphorylase, the first enzyme of glycogen synthesis from
      glucose-1-phosphate. Here, we have analysed a possible regulatory role for the
      transcriptional regulators RamA and RamB on glycogen content of the cells and on
      control of expression of glgC and of glgA, which encodes the second enzyme of
      glycogen synthesis, glycogen synthase. Determination of the glycogen content of
      RamA- and RamB-deficient C. glutamicum indicated that RamA and RamB influence
      glycogen synthesis positively and negatively, respectively. In accordance with
      the identification of putative RamA and RamB binding sites upstream of glgC and
      glgA, both regulators were found to bind specifically to the glgC-glgA intergenic
      promoter region. Promoter activity assays in wild-type and RamA- and RamB
      deficient strains of C. glutamicum revealed that (i) RamA is a positive regulator
      of glgC and glgA, (ii) RamB is a negative regulator of glgA and (iii) neither
      RamA nor RamB alone is responsible for the carbon-source-dependent regulation of
      glycogen synthesis in C. glutamicum.

PMID- 20056700
TI  - Mutations in rpsL that confer streptomycin resistance show pleiotropic effects on
      virulence and the production of a carbapenem antibiotic in Erwinia carotovora.
AB  - Spontaneous streptomycin-resistant derivatives of Erwinia carotovora subsp.
      carotovora strain ATTn10 were isolated. Sequencing of the rpsL locus (encoding
      the ribosomal protein S12) showed that each mutant was missense, with a single
      base change, resulting in the substitution of the wild-type lysine by arginine,
      threonine or asparagine at codon 43. Phenotypic analyses showed that the rpsL
      mutants could be segregated into two groups: K43R mutants showed reduced
      production of the beta-lactam secondary metabolite 1-carbapen-2-em-3 carboxylic
      acid (Car), but little effect on exoenzyme production or virulence in potato
      tuber tests. By contrast, the K43N and K43T mutations were pleiotropic, resulting
      in reduced exoenzyme production and virulence, as well as diminished Car
      production. The effect on Car production was due to reduced transcription of the
      quorum-sensing-dependent car biosynthetic genes. The effects of K43N and K43T
      mutations on Car production were partially alleviated by provision of an excess
      of the quorum-sensing signalling molecule N-(3-oxohexanoyl)-L-homoserine lactone.
      Finally, a proteomic analysis of the K43T mutant indicated that the abundance of
      a subset of intracellular proteins was affected by this rpsL mutation.

PMID- 20056701
TI  - Molecular characterization of FinR, a novel redox-sensing transcriptional
      regulator in Pseudomonas putida KT2440.
AB  - FinR is required for the induction of fpr (ferredoxin-NADP(+) reductase) under
      superoxide stress conditions in Pseudomonas putida. Many proteobacteria harbour
      FinR homologues in their genome as a putative LysR-type protein. Three cysteine
      residues (at positions 150, 239 and 289 in P. putida FinR) are conserved in all
      FinR homologues. When these conserved cysteines, along with two other cysteine
      residues present in FinR, were individually mutated to serines, the FinR remained
      active, unlike SoxR and OxyR in Escherichia coli. The results of our in vitro DNA
      binding assay with cellular extracts showed that FinR binds directly to the fpr
      promoter region. In order to identify the FinR functional domain for sensing
      superoxide stress, we employed random and site-directed mutagenesis of FinR.
      Among 18 single amino acid mutants, three mutants (T39A, R194A and E225A)
      abolished fpr induction without any alteration of their DNA-binding ability,
      whereas other mutants also abrogated their DNA-binding abilities. Interestingly,
      two mutants (L215P and D51A) appeared to be constitutively active, regardless of
      superoxide stress conditions. Ferrous iron depletion, ferric iron addition and
      fdxA (ferredoxin) gene deletion also participate in the regulation of fpr. These
      data indicate that FinR has unusual residues for redox sensing and that the redox
      sensing mechanism of FinR differs from the well-known mechanisms of OxyR and
      SoxR.

PMID- 20056702
TI  - Nitrogen fixation by the verrucomicrobial methanotroph 'Methylacidiphilum
      fumariolicum' SolV.
AB  - The ability to utilize atmospheric nitrogen (N(2)) as a sole nitrogen source is
      an important trait for prokaryotes. Knowledge of N(2) fixation by methanotrophs
      is needed to understand their role in nitrogen cycling in different environments.
      The verrucomicrobial methanotroph 'Methylacidiphilum fumariolicum' strain SolV
      was investigated for its ability to fix N(2). Physiological studies were combined
      with nitrogenase activity measurements and phylogenetic analysis of the nifDHK
      genes, encoding the subunits of the nitrogenase. 'M. fumariolicum' SolV was able
      to fix N(2) at low oxygen (O(2)) concentration (0.5 %, v/v) in chemostat
      cultures. This low oxygen concentration was also required for an optimal
      nitrogenase activity [47.4 nmol ethylene h(-1) (mg cell dry weight)(-1)]. Based
      on acetylene reduction assay and growth experiments, the nitrogenase of strain
      SolV seems to be extremely oxygen sensitive compared to most proteobacterial
      methanotrophs. The activity of the nitrogenase was not inhibited by ammonium
      concentrations up to 94 mM. This is believed to be the first report on the
      physiology of N(2) fixation within the phylum Verrucomicrobia.

PMID- 20056703
TI  - A transcriptome study of the QseEF two-component system and the QseG membrane
      protein in enterohaemorrhagic Escherichia coli O157 : H7.
AB  - QseE is a sensor kinase that responds to epinephrine, sulfate and phosphate. QseE
      constitutes a two-component signalling system together with the QseF sigma(54)
      dependent response regulator. Encoded within the same operon as qseEF is the qseG
      gene, which encodes a membrane protein involved in the translocation of a type
      III secretion effector protein of enterohaemorrhagic Escherichia coli (EHEC) into
      epithelial cells. The qseEGF genes also form an operon with the glnB gene, which
      encodes the E. coli nitrogen sensor PII protein. Here we report a transcriptome
      analysis comparing qseE, qseF andqseG single mutants with the wild-type strain.
      This study revealed that the proteins encoded by these genes play a modest but
      significant role in iron uptake. Although QseEFG regulate genes involved in
      nitrogen utilization, these proteins do not play a notable role in nitrogen
      metabolism. In addition, QseEFG regulate transcription of the rcsBC and phoPQ two
      component systems, linking several signal transduction pathways. The similarity
      of the microarray profiles of these mutants also indicates that these proteins
      work together. These data indicate that QseEFG are involved in the regulation of
      virulence and metabolism in EHEC.

PMID- 20056704
TI  - Staurosporine-induced programmed cell death in Blastocystis occurs independently
      of caspases and cathepsins and is augmented by calpain inhibition.
AB  - Previous studies have shown that the protozoan parasite Blastocystis exhibits
      apoptotic features with caspase-like activity upon exposure to a cytotoxic
      monoclonal antibody or the anti-parasitic drug metronidazole. The present study
      reports that staurosporine (STS), a common apoptosis inducer in mammalian cells,
      also induces cytoplasmic and nuclear features of apoptosis in Blastocystis,
      including cell shrinkage, phosphatidylserine (PS) externalization, maintenance of
      plasma membrane integrity, extensive cytoplasmic vacuolation, nuclear
      condensation and DNA fragmentation. STS-induced PS exposure and DNA fragmentation
      were abolished by the mitochondrial transition pore blocker cyclosporine A and
      significantly inhibited by the broad-range cysteine protease inhibitor
      iodoacetamide. Interestingly, the apoptosis phenotype was insensitive to
      inhibitors of caspases and cathepsins B and L, while calpain-specific inhibitors
      augmented the STS-induced apoptosis response. While the identities of the
      proteases responsible for STS-induced apoptosis warrant further investigation,
      these findings demonstrate that programmed cell death in Blastocystis is complex
      and regulated by multiple mediators.

PMID- 20056705
TI  - Characterization of type IV pili in the life cycle of the predator bacterium
      Bdellovibrio.
AB  - Bdellovibrio and like organisms (BALOs) are obligate prokaryotic predators of
      other Gram-negative bacteria. Bdellovibrio bacteriovorus is the most studied
      organism among BALOs. It has a periplasmic life cycle with two major stages: a
      motile, non-replicative stage spent searching for prey (the attack phase) and a
      stage spent inside the periplasm of the Gram-negative prey cell (the growth
      phase) after forming an osmotically stable body termed the bdelloplast. Within
      Bdellovibrio, there are also strains exhibiting an epibiotic life cycle. The
      genome sequence of the type strain B. bacteriovorus HD100(T) revealed the
      presence of multiple dispersed pil genes encoding type IV pili. Type IV pili in
      other bacteria are involved in adherence to and invasion of host cells and
      therefore can be considered to play a role in invasion of prey cells by
      Bdellovibrio. In this study, genes involved in producing type IV pili were
      identified in the periplasmic strain B. bacteriovorus 109J and an epibiotic
      Bdellovibrio sp. strain JSS. The presence of fibres on attack-phase cells was
      confirmed by examining negative stains of cells fixed with 10% buffered formalin.
      Fibres were at the non-flagellated pole on approximately 25% of attack-phase
      cells. To confirm that these fibres were type IV pili, a truncated form of PilA
      lacking the first 35 amino acids was designed to facilitate purification of the
      protein. The truncated PilA fused to a His-tag was overexpressed in Escherichia
      coli BL21(DE3) plysS. The fusion protein, accumulated in the insoluble fraction,
      was purified under denaturing conditions and used to produce polyclonal antisera.
      Immunoelectron microscopy showed that polar fibres present on the cell surface of
      the predator were composed of PilA, the major subunit of type IV pili.
      Immunofluorescence microscopy showed the presence of pilin on attack-phase cells
      of B. bacteriovorus 109J during attachment to prey cells and just after
      penetration, inside the bdelloplast. Antibodies against PilA delayed and
      inhibited predation in co-cultures of Bdellovibrio. This study confirms that type
      IV pili play a role in invasion of prey cells by Bdellovibrio.

PMID- 20056706
TI  - The microbiology of Lascaux Cave.
AB  - Lascaux Cave (Montignac, France) contains paintings from the Upper Paleolithic
      period. Shortly after its discovery in 1940, the cave was seriously disturbed by
      major destructive interventions. In 1963, the cave was closed due to algal growth
      on the walls. In 2001, the ceiling, walls and sediments were colonized by the
      fungus Fusarium solani. Later, black stains, probably of fungal origin, appeared
      on the walls. Biocide treatments, including quaternary ammonium derivatives, were
      extensively applied for a few years, and have been in use again since January
      2008. The microbial communities in Lascaux Cave were shown to be composed of
      human-pathogenic bacteria and entomopathogenic fungi, the former as a result of
      the biocide selection. The data show that fungi play an important role in the
      cave, and arthropods contribute to the dispersion of conidia. A careful study on
      the fungal ecology is needed in order to complete the cave food web and to
      control the black stains threatening the Paleolithic paintings.

PMID- 20056707
TI  - The major PEP-phosphotransferase systems (PTSs) for glucose, mannose and
      cellobiose of Listeria monocytogenes, and their significance for extra- and
      intracellular growth.
AB  - In this report we examine the PEP-dependent phosphotransferase systems (PTSs) of
      Listeria monocytogenes EGD-e, especially those involved in glucose and cellobiose
      transport. This L. monocytogenes strain possesses in total 86 pts genes, encoding
      29 complete PTSs for the transport of carbohydrates and sugar alcohols, and
      several single PTS components, possibly supporting transport of these compounds.
      By a systematic deletion analysis we identified the major PTSs involved in
      glucose, mannose and cellobiose transport, when L. monocytogenes grows in a
      defined minimal medium in the presence of these carbohydrates. Whereas all four
      PTS permeases belonging to the PTS(Man) family may be involved in mannose
      transport, only two of these (PTS(Man)-2 and PTS(Man)-3), and in addition at
      least one (PTS(Glc)-1) of the five PTS permeases belonging to the PTS(Glc)
      family, are able to transport glucose, albeit with different efficiencies.
      Cellobiose is transported mainly by one (PTS(Lac)-4) of the six members belonging
      to the PTS(Lac) family. In addition, PTS(Glc)-1 appears to be also able to
      transport cellobiose. The transcription of the operons encoding PTS(Man)-2 and
      PTS(Lac)-4 (but not that of the operon for PTS(Man)-3) is regulated by LevR
      homologous PTS regulation domain (PRD) activators. Whereas the growth rate of the
      mutant lacking PTS(Man)-2, PTS(Man)-3 and PTS(Glc)-1 is drastically reduced
      (compared with the wild-type strain) in the presence of glucose, and that of the
      mutant lacking PTS(Lac)-4 and PTS(Glc)-1 in the presence of cellobiose,
      replication of both mutants within epithelial cells or macrophages is as
      efficient as that of the wild-type strain.

PMID- 20056708
TI  - Modulation of transcription and characterization of the promoter organization of
      the autotransporter adhesin heptosyltransferase and the autotransporter adhesin
      AIDA-I.
AB  - In Gram-negative bacteria, autotransporter proteins constitute the largest family
      of secreted proteins, and exhibit many different functions. In recent years,
      research has largely focused on mechanisms of autotransporter protein
      translocation, where several alternative models are still being discussed. In
      contrast, the biogenesis of only a few autotransporters has been studied and,
      likewise, regulation of expression has received only very limited attention. The
      glycosylated autotransporter adhesin involved in diffuse adherence (AIDA)-I
      system consists of the aah gene, encoding a specific autotransporter adhesin
      heptosyltransferase (AAH), and the aidA gene, encoding the autotransporter
      protein (AIDA-I). In this study, we investigated the promoter organization and
      transcription of these two genes using reporter plasmids carrying lacZ
      transcriptional fusions. The two genes, aah and aidA, are transcribed as a
      bicistronic message. However, aidA is additionally transcribed from its own
      promoter. There are two distinct start sites for each of the two genes.
      Interestingly, transcription of both genes is enhanced in hns and rfaH mutant
      backgrounds. Furthermore, we addressed the influence of environmental factors and
      different genetic backgrounds of Escherichia coli K-12 strains on transcription
      activity. We found that transcription varied considerably in different E. coli K
      12 laboratory strains and under different growth conditions.

PMID- 20056712
TI  - Sources of funding for Nobel Prize-winning work: public or private?
AB  - Funding is important for scientists' work and may contribute to exceptional
      research outcomes. We analyzed the funding sources reported in the landmark
      scientific papers of Nobel Prize winners. Between 2000 and 2008, 70 Nobel
      laureates won recognition in medicine, physics, and chemistry. Sixty five (70%)
      of the 93 selected papers related to the Nobel-awarded work reported some funding
      source including U.S. government sources in 53 (82%), non-U.S. government sources
      in 19 (29%), and nongovernment sources in 33 (51%). A substantial portion of this
      exceptional work was unfunded. We contacted Nobel laureates whose landmark papers
      reported no funding. Thirteen Nobel laureates responded and offered their
      insights about the funding process and difficulties inherent in funding. Overall,
      very diverse sources amounting to a total of 64 different listed sponsors
      supported Nobel-related work. A few public institutions, in particular the U.S.
      National Institutes of Health (with n=26 funded papers) and the National Science
      Foundation (with n=17 papers), stood out for their successful record for funding
      exceptional research. However, Nobel-level work arose even from completely
      unfunded research, especially when institutions offered a protected environment
      for dedicated scientists.

PMID- 20056711
TI  - Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a
      melanosome-specific and proteolytically released protein.
AB  - Melanosomes are organelles specialized for the production of melanin pigment and
      are specifically produced by melanocytic cells. More than 150 pigmentation
      related genes have been identified, including glycoprotein nonmetastatic melanoma
      protein b (GPNMB). A recent proteomics analysis revealed that GPNMB is localized
      in melanosomes, and GPNMB is a membrane-bound glycoprotein that shows high
      homology with a well-known melanosomal structural protein, Pmel17/gp100. In this
      study, we show that GPNMB is expressed in melanocytes of normal human skin, as
      well as in human melanoma cells. GPNMB is heavily glycosylated and is enriched in
      mature (stage III and IV) melanosomes in contrast to MART-1 and Pmel17, which are
      abundant in early (stage I and II) melanosomes. MART-1 and Pmel17 play critical
      roles in the maturation of early melanosomes; thus, we speculate that GPNMB might
      be important in the functions of late melanosomes, possibly their transport
      and/or transfer to keratinocytes. We also demonstrate that a secreted form of
      GPNMB is released by ectodomain shedding from the largely Golgi-modified form of
      GPNMB and that the PKC and Ca(2+) intracellular signaling pathways regulate that
      shedding. We conclude that GPNMB is a melanosomal protein that is released by
      proteolytic ectodomain shedding and might be a useful and specific histological
      marker of melanocytic cells.

PMID- 20056714
TI  - Correlations between progression of coronary artery disease and circulating
      endothelial progenitor cells.
AB  - The pathophysiology of coronary artery disease (CAD) progression is not well
      understood. Endothelial progenitor cells (EPCs) may have an important role. In
      the present observational cohort study we assessed the number of circulating EPCs
      in 136 patients undergoing elective percutaneous coronary intervention and who
      had at least one major epicardial vessel with a nonsignificant stenosis [<50%
      diameter stenosis (DS)], and the relationship between plasma EPC levels and the
      24-mo progression of the nonsignificant coronary artery lesion. The following
      cell populations were analyzed: CD34(+), CD133(+), CD34(+)/KDR(+), CD34(+)/VE
      cadherin(+), and endothelial cell colony-forming units (CFU-ECs). Progression was
      defined as a >15% DS increase of the objective vessel at follow-up. At 24 mo, 57
      patients (42%) experienced significant progression. Independent predictors of
      disease progression were LDL cholesterol > 100 mg/dl (OR=1.03; 95% CI 1.01-1.04;
      P=0.001), low plasma levels of CFU-ECs (OR=3.99; 95% CI 1.54-10.37; P=0.005), and
      male sex (OR=3.42; 95% CI 1.15-10.22; P=0.027). Circulating levels of EPCs are
      significantly lower in patients with angiographic CAD progression.

PMID- 20056713
TI  - An EGFR autocrine loop encodes a slow-reacting but dominant mode of
      mechanotransduction in a polarized epithelium.
AB  - The mechanical landscape in biological systems can be complex and dynamic, with
      contrasting sustained and fluctuating loads regularly superposed within the same
      tissue. How resident cells discriminate between these scenarios to respond
      accordingly remains largely unknown. Here, we show that a step increase in
      compressive stress of physiological magnitude shrinks the lateral intercellular
      space between bronchial epithelial cells, but does so with strikingly slow
      exponential kinetics (time constant approximately 110 s). We confirm that
      epidermal growth factor (EGF)-family ligands are constitutively shed into the
      intercellular space and demonstrate that a step increase in compressive stress
      enhances EGF receptor (EGFR) phosphorylation with magnitude and onset kinetics
      closely matching those predicted by constant-rate ligand shedding in a slowly
      shrinking intercellular geometry. Despite the modest degree and slow nature of
      EGFR activation evoked by compressive stress, we find that the majority of
      transcriptomic responses to sustained mechanical loading require ongoing activity
      of this autocrine loop, indicating a dominant role for mechanotransduction
      through autocrine EGFR signaling in this context. A slow deformation response to
      a step increase in loading, accompanied by synchronous increases in ligand
      concentration and EGFR activation, provides one means for cells to mount a
      selective and context-appropriate response to a sustained change in mechanical
      environment.

PMID- 20056715
TI  - Genetic deficiency of Irgm1 (LRG-47) suppresses induction of experimental
      autoimmune encephalomyelitis by promoting apoptosis of activated CD4+ T cells.
AB  - The immunity-related GTPase Irgm1, also called LRG-47, is known to regulate host
      resistance to intracellular pathogens through multiple mechanisms that include
      controlling the survival of T lymphocytes. Here, we address whether Irgm1 also
      plays a role in the pathogenesis of experimental autoimmune encephalitis (EAE).
      We find that Irgm1/LRG-47 is a significant factor in the progression of EAE and
      multiple sclerosis (MS). Expression of Irgm1 was robustly elevated in MS-affected
      lesions and in the central nervous system (CNS) of myelin basic protein (MBP)
      induced EAE mice, especially in cells of lymphoid and mononuclear phagocyte
      origin. Homozygous Irgm1 null mice were resistant to MBP-induced EAE, and CD4(+)
      T cells in spleen and CNS of these mice displayed decreased proliferative
      capacity, increased apoptosis, and up-regulated interferon (IFN)-gamma induction.
      Therefore, Irgm1-induced survival of autoreactive CD4(+) T cells contributes
      significantly to the pathogenesis of EAE. Blockade of Irgm1 may be a potential
      therapeutic strategy for halting multiple sclerosis.

PMID- 20056716
TI  - Fluorosomes: a convenient new reagent to detect and block multivalent and complex
      receptor-ligand interactions.
AB  - We describe for the first time fluorescent virus-like particles decorated with
      biologically active mono- and multisubunit immune receptors of choice and the
      basic application of such fluorosomes (FSs) to visualize and target immune
      receptor-ligand interactions. For that purpose, human embryonic kidney (HEK)-293
      cells were stably transfected with Moloney murine leukemia virus (MoMLV) matrix
      protein (MA) GFP fusion constructs. To produce FSs, interleukins (ILs), IL
      receptors (IL-Rs), and costimulatory molecules were fused to the glycosyl
      phosphatidyl inositol anchor acceptor sequence of CD16b and coexpressed along
      with MoMLV group-specific antigen-polymerase (gag-pol) in MA::GFP(+) HEK-293
      cells. We show that IL-2 decorated but not control-decorated FSs specifically
      identify normal and malignant IL-2 receptor-positive (IL-2R(+)) lymphocytes by
      flow cytometry. In addition to cytokines and costimulatory molecules, FSs were
      also successfully decorated with the heterotrimeric IL-2Rs, allowing
      identification of IL-2(+) target cells. Specificity of binding was proven by
      complete inhibition with nonlabeled, soluble ligands. Moreover, IL-2R FSs
      efficiently neutralized soluble IL-2 and thus induced unresponsiveness of T cells
      receiving full activation stimuli via T-cell antigen receptor and CD28. FSs are
      technically simple, multivalent tools for assessing and blocking mono- and
      multisubunit immune receptor-ligand interactions with natural constituents in a
      plasma membrane context.

PMID- 20056718
TI  - Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha
      dependent manner.
AB  - Stringent control of immune responses in the intestinal mucosa is critical for
      the maintenance of immune homeostasis and prevention of tissue damage, such as
      observed during inflammatory bowel disease. Intestinal epithelial cells,
      primarily thought to form a simple physical barrier, critically regulate
      intestinal immune cell functions by producing immunoregulatory glucocorticoids on
      T-cell activation. In this study we investigated whether stimulation of cells of
      the innate immune system results in the induction of intestinal glucocorticoids
      synthesis and what role TNF-alpha plays in this process. Stimulation of the
      innate immune system with lipopolysaccharide (LPS) led to an up-regulation of
      colonic steroidogenic enzymes and the induction of intestinal glucocorticoid
      synthesis. The observed induction was dependent on macrophage effector functions,
      as depletion of macrophages using clodronate-containing liposomes, but not
      absence of T and B cells, inhibited intestinal glucocorticoid synthesis. LPS
      induced glucocorticoid synthesis was critically dependent on TNF-alpha as it was
      significantly decreased in TNF-alpha-deficient animals. Both TNF receptor-1 and 
      2 were found to be equally involved in LPS- and T-cell-induced intestinal GC
      synthesis. These results describe a novel and critical role of TNF-alpha in
      immune cell-induced intestinal glucocorticoid synthesis.

PMID- 20056717
TI  - MicroRNA-204/211 alters epithelial physiology.
AB  - MicroRNA (miRNA) expression in fetal human retinal pigment epithelium (hfRPE),
      retina, and choroid were pairwise compared to determine those miRNAs that are
      enriched by 10-fold or more in each tissue compared with both of its neighbors.
      miRs-184, 187, 200a/200b, 204/211, and 221/222 are enriched in hfRPE by 10- to
      754-fold compared with neuroretina or choroid (P<0.05). Five of these miRNAs are
      enriched in RPE compared with 20 tissues throughout the body and are 10- to
      20,000-fold more highly expressed (P<0.005). miR-204 and 211 are the most highly
      expressed in the RPE. In addition, expression of miR-204/211 is significantly
      lower in the NCI60 tumor cell line panel compared with that in 13 normal tissues,
      suggesting the progressive disruption of epithelial barriers and increased
      proliferation. We demonstrated that TGF-beta receptor 2 (TGF-betaR2) and SNAIL2
      are direct targets of miR-204 and that a reduction in miR-204 expression leads to
      reduced expression of claudins 10, 16, and 19 (message/protein) consistent with
      our observation that anti-miR-204/211 decreased transepithelial resistance by 80%
      and reduced cell membrane voltage and conductance. The anti-miR-204-induced
      decrease in Kir7.1 protein levels suggests a signaling pathway that connects TGF
      betaR2 and maintenance of potassium homeostasis. Overall, these data indicate a
      critical role for miR-204/211 in maintaining epithelial barrier function and cell
      physiology.

PMID- 20056719
TI  - Progressive resistance training improves overall physical activity levels in
      patients with early osteoarthritis of the knee: a randomized controlled trial.
AB  - BACKGROUND: Prescription of resistance training (RT) exercises is an essential
      aspect of management for knee osteoarthritis (OA). However, whether patients with
      knee OA who are randomly assigned to receive RT simply substitute RT for other
      modes of physical activity remains unclear. OBJECTIVE: The aim of this study was
      to determine the effect of a structured RT intervention on overall levels of
      moderate- and vigorous-intensity physical activity (MVPA) in patients with early
      onset knee OA. The study compared patients with early-onset OA who participated
      in an RT program, those who participated in a self-management (SM) program, and
      those who participated in both RT and SM. Because participants randomly assigned
      to receive the RT intervention may simply switch activity modes, resulting in
      little net effect, we assessed total MVPA in addition to tracking changes in
      strength (force-generating capacity). DESIGN AND INTERVENTION: This study was a
      randomized controlled trial comparing the effectiveness of SM alone, RT alone,
      and combined RT+SM on MVPA in patients with early OA of the knee. SETTING: The
      study was conducted on a university campus, with patient recruitment from the
      local community. PARTICIPANTS: The participants in this study were 171 patients
      (74% women, 26% men) with knee OA. They had a mean age of 55.1 (SD=7.1) years, a
      mean body mass index of 27.6 (SD=4.2) kg/m(2), and radiographic status of grade
      II OA (and no higher) in at least one knee, as defined by the Kellgren and
      Lawrence classification. They wore an accelerometer while awake (X=14.2 [SD=2.2]
      hours) for 5 to 7 contiguous days (X=6.8 [SD=0.5] days) at baseline and at 3 and
      9 months of intervention. RESULTS: The participants engaged in MVPA a mean of
      26.2 (SD=19.3) minutes per day at baseline. Both groups significantly increased
      their MVPA from baseline to 3 months (RT group by 18% [effect size (d)=0.26]; SM
      group by 22% [effect size (d)=0.25]), but only the RT group sustained those
      changes at 9 months (RT group maintained a 10% increase [effect size (d)=0.15];
      SM group maintained a 2% increase [effect size (d)=0.03]). A significant group x
      time interaction for MVPA indicated that the RT group maintained higher MVPA
      levels than the SM group. LIMITATIONS: Lack of direct measures of energy
      expenditure and physical function was a limitation of the study. CONCLUSIONS:
      Patients with early-onset OA of the knee can engage in an RT program without
      sacrificing their overall MVPA levels. These results support the value of RT for
      management of knee OA.

PMID- 20056720
TI  - An exercise and education program improves well-being of new mothers: a
      randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of a physical
      therapy exercise and health care education program on the psychological well
      being of new mothers. DESIGN: This was a randomized controlled trial.
      PARTICIPANTS: Primiparous and multiparous English-speaking women ready for
      discharge from The Angliss Hospital postnatal ward were eligible for this study.
      Women who were receiving psychiatric care were excluded. One hundred sixty-one
      women were randomized into the trial. INTERVENTION: The experimental group (n=62)
      received an 8-week "Mother and Baby" (M&B) program, including specialized
      exercise provided by a women's health physical therapist combined with parenting
      education. The other group (education only [EO], n=73) received only the same
      educational material as the experimental group. MAIN OUTCOME MEASURES:
      Psychological well-being (Positive Affect Balance Scale), depressive symptoms
      (Edinburgh Postnatal Depression Scale), and physical activity levels were
      assessed at baseline, after 8 weeks (post-program), and then 4 weeks later.
      RESULTS: There was significant improvement in well-being scores and depressive
      symptoms of the M&B group compared with the EO group over the study period. More
      specifically, there was a significant positive effect on well-being scores and
      depressive symptoms at 8 weeks, and this effect was maintained 4 weeks after
      completion of the program. The number of women identified as "at risk" for
      postnatal depression pre-intervention was reduced by 50% by the end of the
      intervention. LIMITATIONS: Although this study provides promising short-term (4
      week) outcomes, further work is needed to explore whether the intervention
      effects are maintained as sustained psychological and behavioral benefits at 6
      months. CONCLUSIONS: A physical therapy exercise and health education program is
      effective in improving postnatal well-being. Routine use of this program may
      reduce longer-term problems such as postnatal depression.

PMID- 20056721
TI  - Balance impairment as a risk factor for falls in community-dwelling older adults
      who are high functioning: a prospective study.
AB  - BACKGROUND: Screening should have simple and easy-to-administer methods that
      identify impairments associated with future fall risk, but there is a lack of
      literature supporting validation for their use. OBJECTIVE: The aim of this study
      was to evaluate the independent contribution of balance assessment on future fall
      risk, using 5 methods to quantify balance impairment, for the outcomes "any fall"
      and "any injurious fall" in community-dwelling older adults who are higher
      functioning. DESIGN: This was a prospective cohort study. METHODS: A sample of
      210 community-dwelling older adults (70% male, 30% female; mean age=79.9 years,
      SD=4.7) received a comprehensive geriatric assessment at baseline, which included
      the Berg Balance Scale to measure balance. Information on daily falls was
      collected for 12 months by each participant's monthly submission of a falls log
      calendar. RESULTS: Seventy-eight people (43%) fell, of whom 54 (30%) sustained an
      injurious fall and 32 (18%) had recurrent falls (> or =2 falls). Different
      balance measurement methods identified different numbers of people as impaired.
      Adjusted relative risk (RR) estimates for an increased risk of any fall were 1.58
      (95% confidence interval [CI]=1.06, 2.35) for self-report of balance problems,
      1.58 (95% CI=1.03, 2.41) for one-leg stance, and 1.46 (95% CI=1.02, 2.09) for
      limits of stability. An adjusted RR estimate for an increased risk of an
      injurious fall of 1.95 (95% CI=1.15, 3.31) was found for self-report of balance
      problems. Limitations The study was a secondary analysis of data. CONCLUSIONS:
      Not all methods of evaluating balance impairment are associated with falls. The
      number of people identified as having balance impairment varies with the
      measurement tool; therefore, the measurement tools are not interchangeable or
      equivalent in defining an at-risk population. The thresholds established in this
      study indicate individuals who should receive further comprehensive fall
      assessment and treatment to prevent falls.

PMID- 20056722
TI  - Physical therapy in the emergency department: development of a novel practice
      venue.
AB  - BACKGROUND AND PURPOSE: The American Physical Therapy Association's Vision 2020
      advocates that physical therapists be integral members of health care teams
      responsible for diagnosing and managing movement and functional disorders. This
      report details the design and early implementation of a physical therapist
      service in the emergency department (ED) of a large, urban hospital and presents
      recommendations for assessing the effectiveness of physical therapists in this
      setting. CASE DESCRIPTION: Emergency departments serve multiple purposes in the
      American health care system, including care of patients with non-life-threatening
      illnesses. Physical therapists have expertise in screening for problems that are
      not amenable to physical therapy and in addressing a wide range of acute and
      chronic musculoskeletal pain problems. This expertise invites inclusion into the
      culture of ED practice. This administrative case report describes planning and
      early implementation of a physical therapist practice in an ED, shares
      preliminary outcomes, and provides suggestions for expansion and effectiveness
      testing of practice in this novel venue. OUTCOMES: Referrals have increased and
      length of stay has decreased for patients receiving physical therapy. Preliminary
      surveys suggest high patient and practitioner satisfaction with physical therapy
      services. Outpatient physical therapy follow-up options were developed. Educating
      ED personnel to triage patients who show deficits in pain and functional mobility
      to physical therapy has challenged the usual culture of ED processes. DISCUSSION:
      Practice in the hospital ED enables physical therapists to fully use their
      knowledge, diagnostic skills, and ability to manage acute pain and
      musculoskeletal injury. Recommendations for future action are made to encourage
      more institutions across the country to incorporate physical therapy in EDs to
      enhance the process and outcome of nonemergent care.

PMID- 20056723
TI  - Understanding protein phosphorylation on a systems level.
AB  - Protein kinase phosphorylation is central to the regulation and control of
      protein and cellular function. Over the past decade, the development of many high
      throughput approaches has revolutionized the understanding of protein
      phosphorylation and allowed rapid and unbiased surveys of phosphoproteins and
      phosphorylation events. In addition to this technological advancement, there have
      also been computational improvements; recent studies on network models of protein
      phosphorylation have provided many insights into the cellular processes and
      pathways regulated by phosphorylation. This article gives an overview of
      experimental and computational techniques for identifying and analyzing protein
      phosphorylation on a systems level.

PMID- 20056724
TI  - Phase II metabolism of hesperetin by individual UDP-glucuronosyltransferases and
      sulfotransferases and rat and human tissue samples.
AB  - Phase II metabolism by UDP-glucuronosyltransferases (UGTs) and sulfotransferases
      (SULTs) is the predominant metabolic pathway during the first-pass metabolism of
      hesperetin (4'-methoxy-3',5,7-trihydroxyflavanone). In the present study, we have
      determined the kinetics for glucuronidation and sulfonation of hesperetin by 12
      individual UGT and 12 individual SULT enzymes as well as by human or rat small
      intestinal, colonic, and hepatic microsomal and cytosolic fractions. Results
      demonstrate that hesperetin is conjugated at positions 7 and 3' and that major
      enzyme-specific differences in kinetics and regioselectivity for the UGT and SULT
      catalyzed conjugations exist. UGT1A9, UGT1A1, UGT1A7, UGT1A8, and UGT1A3 are the
      major enzymes catalyzing hesperetin glucuronidation, the latter only producing 7
      O-glucuronide, whereas UGT1A7 produced mainly 3'-O-glucuronide. Furthermore,
      UGT1A6 and UGT2B4 only produce hesperetin 7-O-glucuronide, whereas UGT1A1,
      UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15 conjugate both positions. SULT1A2
      and SULT1A1 catalyze preferably and most efficiently the formation of hesperetin
      3'-O-sulfate, and SULT1C4 catalyzes preferably and most efficiently the formation
      of hesperetin 7-O-sulfate. Based on expression levels SULT1A3 and SULT1B1 also
      will probably play a role in the sulfo-conjugation of hesperetin in vivo. The
      results help to explain discrepancies in metabolite patterns determined in
      tissues or systems with different expression of UGTs and SULTs, e.g., hepatic and
      intestinal fractions or Caco-2 cells. The incubations with rat and human tissue
      samples support an important role for intestinal cells during first-pass
      metabolism in the formation of hesperetin 3'-O-glucuronide and 7-O-glucuronide,
      which appear to be the major hesperetin metabolites found in vivo.

PMID- 20056725
TI  - Identification of the UDP-glucuronosyltransferase isozyme involved in senecionine
      glucuronidation in human liver microsomes.
AB  - Senecionine (SEN) is a representative of the hepatotoxic pyrrolizidine alkaloids.
      Although phase I metabolism for cytochrome P450-mediated metabolic activation of
      SEN was investigated extensively, phase II metabolism for glucuronidation of this
      compound has not been investigated until now. In our present study, one unique
      glucuronidation product of SEN in human liver microsomes (HLMs) was identified as
      SEN N-glucuronide using an authentically synthesized product for which the
      structure was identified via (1)H and (13)C NMR analysis. Subsequently, kinetics
      indicated that SEN N-glucuronidation followed the typical Michaelis-Menten model
      and only one major isozyme participated in it. Finally, this isozyme was
      demonstrated to be UDP-glucuronosyltransferase (UGT) 1A4, with the direct
      evidence that recombinant UGT1A4 exhibited predominant and exclusive activity on
      SEN N-glucuronidation. This result was confirmed by other experiments including
      chemical inhibition by selective inhibitors and a correlation study between
      activities of SEN N-glucuronidation and various UGT isozymes. The exclusive role
      of UGT1A4 on SEN N-glucuronidation was strengthened additionally by its
      inhibitory kinetic study in which the selective inhibitor of UGT1A4 showed a
      similar inhibition pattern and K(i) values in both HLM and recombinant UGT1A4
      systems. Because UGT2B10 activity failed to correlate with SEN N-glucuronidation
      in HLMs from 10 individuals, it was impossible for UGT2B10 to play an important
      role in this metabolism.

PMID- 20056726
TI  - Minding the store of Ca2+ during ischaemia/reperfusion.

PMID- 20056727
TI  - HO-1, a new target of PPARdelta with 'anti-atherogenic' properties: is it the
      one?

PMID- 20056728
TI  - Developing computational model-based diagnostics to analyse clinical chemistry
      data.
AB  - This article provides methodological and technical considerations to researchers
      starting to develop computational model-based diagnostics using clinical
      chemistry data. These models are of increasing importance, since novel
      metabolomics and proteomics measuring technologies are able to produce large
      amounts of data that are difficult to interpret at first sight, but have high
      diagnostic potential. Computational models aid interpretation and make the data
      accessible for clinical diagnosis. We discuss the issues that a modeller has to
      take into account during the design, construction and evaluation phases of model
      development. We use the example of Particle Profiler development, a model-based
      diagnostic tool for lipoprotein disorders, as a case study, to illustrate our
      considerations. The case study also offers techniques for efficient model
      formulation, model calculation, workflow structuring and quality control.

PMID- 20056729
TI  - Online tools for understanding rat physiology.
AB  - Rat models have been used to investigate physiological and pathophysiological
      mechanisms for decades. With the availability of the rat genome and other online
      resources, tools to identify rat models that mimic human disease are an important
      step in translational research. Despite the large number of papers published each
      year using rat models, integrating this information remains a problem. Resources
      for the rat genome are continuing to grow rapidly, while resources providing
      access to rat phenotype data are just emerging. An overview of rat models of
      disease, tools to characterize strain by phenotype and genotype, and steps being
      taken to integrate rat physiological data is presented in this article.
      Integrating functional and physiological data with the rat genome will build a
      solid research platform to facilitate innovative studies to unravel the
      mechanisms resulting in disease.

PMID- 20056730
TI  - Comparative study of computational methods to detect the correlated reaction sets
      in biochemical networks.
AB  - Correlated reaction sets (Co-Sets) are mathematically defined modules in
      biochemical reaction networks which facilitate the study of biological processes
      by decomposing complex reaction networks into conceptually simple units.
      According to the degree of association, Co-Sets can be classified into three
      types: perfect, partial and directional. Five approaches have been developed to
      calculate Co-Sets, including network-based pathway analysis, Monte Carlo
      sampling, linear optimization, enzyme subsets and hard-coupled reaction sets.
      However, differences in design and implementation of these methods lead to
      discrepancies in the resulted Co-Sets as well as in their use in biotechnology
      which need careful interpretation. In this paper, we provide a comparative study
      of the methods for Co-Sets computing in detail from four aspects: (i)
      sensitivity, (ii) completeness and soundness, (iii) flexibility and (iv)
      scalability. By applying them to Escherichia coli core metabolic network, the
      differences and relationships among these methods are clearly articulated which
      may be useful for potential users.

PMID- 20056731
TI  - CaliBayes and BASIS: integrated tools for the calibration, simulation and storage
      of biological simulation models.
AB  - Dynamic simulation modelling of complex biological processes forms the backbone
      of systems biology. Discrete stochastic models are particularly appropriate for
      describing sub-cellular molecular interactions, especially when critical
      molecular species are thought to be present at low copy-numbers. For example,
      these stochastic effects play an important role in models of human ageing, where
      ageing results from the long-term accumulation of random damage at various
      biological scales. Unfortunately, realistic stochastic simulation of discrete
      biological processes is highly computationally intensive, requiring specialist
      hardware, and can benefit greatly from parallel and distributed approaches to
      computation and analysis. For these reasons, we have developed the BASIS system
      for the simulation and storage of stochastic SBML models together with associated
      simulation results. This system is exposed as a set of web services to allow
      users to incorporate its simulation tools into their workflows. Parameter
      inference for stochastic models is also difficult and computationally expensive.
      The CaliBayes system provides a set of web services (together with an R package
      for consuming these and formatting data) which addresses this problem for SBML
      models. It uses a sequential Bayesian MCMC method, which is powerful and
      flexible, providing very rich information. However this approach is exceptionally
      computationally intensive and requires the use of a carefully designed
      architecture. Again, these tools are exposed as web services to allow users to
      take advantage of this system. In this article, we describe these two systems and
      demonstrate their integrated use with an example workflow to estimate the
      parameters of a simple model of Saccharomyces cerevisiae growth on agar plates.

PMID- 20056732
TI  - Motor vehicle collisions involving child pedestrians in eThekwini in 2007.
AB  - The burden of disability and death on child pedestrians has not been widely
      researched in the developing world. Using the eThekwini Transport Authority
      database for 2007, data about collisions involving pedestrians under the age of
      15 in the eThekwini metropolitan area were analysed. Incidence risk and
      proportions were calculated for risk factors involving pedestrians, drivers and
      the environment. Male pedestrians aged 5 to 9 were at highest risk of injury
      compared to other male pedestrians (IRR: 1.63; 95% CI: 1.38 to 1.91). This group
      also had the highest fatality risk (IRR: 2.12; 95% CI: 1.05 to 4.29). Male
      drivers had nearly five times the risk of involvement in pedestrian collisions
      compared to females. The highest proportion of fatal pedestrian collisions
      involved buses and trucks, on freeways, in wet conditions and at night. The
      findings point to the need to: (a) improve pedestrian visibility; (b) design safe
      routes to schools; and (c) develop practical roadside skills. For the first time
      in research in road traffic injuries, this study provides an overall picture of
      both fatal and non-fatal child pedestrian collisions in a South African
      municipality.

PMID- 20056733
TI  - Exercise limitation in interstitial lung disease - mechanisms, significance and
      therapeutic options.
AB  - Exercise limitation is a cardinal feature of the interstitial lung diseases and
      is frequently associated with marked dyspnoea on exertion. People with
      interstitial lung disease exhibit a rapid, shallow breathing pattern during
      exercise that worsens as disease progresses. Despite this, ventilatory mechanics
      are not the major limitation to exercise in most patients, with impaired gas
      exchange and circulatory limitation playing a more important role. Peripheral and
      respiratory muscle dysfunction may also contribute to impaired exercise
      tolerance, either due to systemic manifestations of the underlying disease,
      treatment side-effects or deconditioning. Measures of exercise capacity or
      desaturation obtained from maximal and submaximal exercise tests are good
      predictors of survival in patients with idiopathic pulmonary fibrosis. However,
      to date few pharmaceutical treatments have affected exercise outcomes despite
      improvements in other important clinical markers. Supplemental oxygen acutely
      improves exercise capacity in interstitial lung disease and is recommended for
      hypoxic patients, although quality of life or survival benefits have not yet been
      demonstrated. Exercise training improves walking capacity and dyspnoea in short
      term trials and is useful to maximize functional capacity. The role of exercise
      testing in the routine management of patients with interstitial lung disease is
      not clearly defined. However, given the poor prognosis in patients with
      idiopathic pulmonary fibrosis and the marked variation in clinical course,
      assessment of exercise capacity may provide useful information for both
      clinicians and patients when evaluating the risks and benefits of new treatments.
      The extent of resting or exercise-induced hypoxia in patients with interstitial
      lung disease may influence the selection of an appropriate exercise test, and
      oxygen administration should be standardized on repeat testing.

PMID- 20056734
TI  - Taurine reduces FK506-induced generation of ROS and activation of JNK and Bax in
      Madin Darby canine kidney cells.
AB  - The immunosuppressive compound FK506 has been successfully used in kidney and
      liver transplant recipients. However, the compound can induce significant side
      effects on kidney function. Taurine is a potent free radical scavenger that
      attenuates a variety of renal diseases that are the consequence of excessive
      oxygen free radical damage. The purpose of this study was to investigate FK506
      mediated death of Madin Darby canine kidney (MDCK) cells, in relation to reactive
      oxygen species (ROS) production. We determined the calcium (Ca(2+)) and magnesium
      (Mg(2+)) concentration in cultured MDCK cells by microfluorescence techniques and
      the level of activation of c-Jun-N-terminal kinase (JNK), extracellular signal
      regulated kinases (ERK), Bcl-2 and Bax proteins by Western blot. Treatment with
      10 muM FK506 induced apoptosis in MDCK cells by increasing the level of
      intracellular ROS and Ca(2+) and by decreaseing the level of intracellular
      Mg(2+). This increase in intracellular ROS promoted JNK and Bax activation, which
      increased FK506-induced MDCK cell death. Taurine reduced the FK506-induced
      generation of ROS and activation of JNK and Bax. The results indicate that
      taurine can prevent FK506-induced kidney toxicity.

PMID- 20056735
TI  - Protective effects of fomepizole on 2-chloroethanol toxicity.
AB  - 2-Chloroethanol (2-CE) is a widely used industrial solvent. In Taiwan, Taiwanese
      farmers apply 2-CE on grape-vines to accelerate grape growth, a practice that in
      some cases have caused poisoning in humans. Thus, there is strong interest in
      identifying antidotes to 2-CE. This study examines the protective role in 2-CE
      intoxicated rats. Alcohol dehydrogenase and glutathione were hypothesized to be
      important in the metabolism of 2-CE. This study used fomepizole, an alcohol
      dehydrogenase inhibitor, and chemicals that affected glutathione metabolism to
      study 2-CE toxicity. Notably, fomepizole 5 mg/kg significantly increased median
      lethal dose (LD(50)) of 2-CE from 65.1 to 180 mg/kg and reduced the production of
      a potential toxic metabolite chloroacetaldehyde (CAA) in animal plasma. In
      contrast, disulfiram (DSF), an aldehyde dehydrogenase inhibitor, increased the
      toxicity of 2-CE on the lethality in rats. Additional or pretreatment with N
      acetylcysteine (NAC) and fomepizole significantly reduced plasma CAA
      concentrations. Fomepizole also significantly reduced 2-CEinhibited glutathione
      activity. Otherwise, pretreatment with NAC for 4 days followed by co-treatment
      with fomepizole significantly decreased formation of the metabolic CAA. These
      results indicated that its catalytic enzyme might play a vital role during 2-CE
      intoxication, and the combination of fomepizole and NAC could be a protective
      role in cases of acute 2-CE intoxication.

PMID- 20056736
TI  - Curcumin protects DNA damage in a chronically arsenic-exposed population of West
      Bengal.
AB  - Groundwater arsenic contamination has been a health hazard for West Bengal,
      India. Oxidative stress to DNA is recognized as an underlying mechanism of
      arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be
      potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin
      could be an effective strategy to combat arsenic toxicity. This field trial in
      Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic
      effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay
      and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by
      high performance liquid chromatography (HPLC). Arsenic induced oxidative stress
      and elucidation of the antagonistic role of curcumin was done by observation on
      reactive oxygen species (ROS) generation, lipid peroxidation and protein
      carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione
      reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic
      glutathione were also analyzed. The blood samples of the endemic regions showed
      severe DNA damage with increased levels of ROS and lipid peroxidation. The
      antioxidants were found with depleted activity. Three months curcumin
      intervention reduced the DNA damage, retarded ROS generation and lipid
      peroxidation and raised the level of antioxidant activity. Thus curcumin may have
      some protective role against the DNA damage caused by arsenic.

PMID- 20056737
TI  - Troponin I, the story.

PMID- 20056738
TI  - A novel FMR1 PCR method for the routine detection of low abundance expanded
      alleles and full mutations in fragile X syndrome.
AB  - BACKGROUND: Fragile X syndrome (FXS) is a trinucleotide-repeat disease caused by
      the expansion of CGG sequences in the 5' untranslated region of the FMR1 (fragile
      X mental retardation 1) gene. Molecular diagnoses of FXS and other emerging FMR1
      disorders typically rely on 2 tests, PCR and Southern blotting; however,
      performance or throughput limitations of these methods currently constrain
      routine testing. METHODS: We evaluated a novel FMR1 gene-specific PCR technology
      with DNA templates from 20 cell lines and 146 blinded clinical samples. The CGG
      repeat number was determined by fragment sizing of PCR amplicons with capillary
      electrophoresis, and results were compared with those for FMR1 Southern blotting
      analyses with the same samples. RESULTS: The FMR1 PCR accurately detected full
      mutation alleles up to at least 1300 CGG repeats and consisting of >99% GC
      character. All categories of alleles detected by Southern blotting, including 66
      samples with full mutations, were also identified by the FMR1 PCR for each of the
      146 clinical samples. Because all full mutation alleles in samples from
      heterozygous females were detected by the PCR, allele zygosity was reconciled in
      every case. The PCR reagents also detected a 1% mass fraction of a 940-CGG allele
      in a background of 99% 23-CGG allele-a roughly 5- fold greater sensitivity than
      obtained with Southern blotting. CONCLUSIONS: The novel PCR technology can
      accurately categorize the spectrum of FMR1 alleles, including alleles previously
      considered too large to amplify; reproducibly detect low abundance full mutation
      alleles; and correctly infer homozygosity in female samples, thus greatly
      reducing the need for sample reflexing to Southern blotting.

PMID- 20056739
TI  - Evaluation of the PAX8/PPARG translocation in follicular thyroid cancer with a 4
      color reverse-transcription PCR assay and automated high-resolution fragment
      analysis.
AB  - BACKGROUND: Molecular testing of thyroid malignancies, in combination with
      cytologic and histologic examination, is becoming increasingly attractive as a
      tool for refining traditional morphologic diagnosis. The molecular changes
      associated with follicular thyroid carcinoma (FTC) are point mutations in RAS
      oncogenes or the presence of PAX8/PPARG (paired box 8/peroxisome proliferator
      activated receptor gamma) rearrangement. METHODS: We developed and validated a
      clinical assay for the detection of PAX8/PPARG rearrangements that uses a 4-color
      reverse-transcription PCR (RT-PCR) assay and high-resolution fragment analysis.
      RESULTS: The RT-PCR assay is applicable for detecting the various described
      fusion transcripts of PAX8/PPARG in formalin-fixed, paraffin-embedded thyroid
      tissue and in fine-needle aspirate biopsy washes from thyroid nodules. The
      analytical sensitivity of the assay is 1 abnormal cell in a background of 100-10
      000 translocation-negative cells. A comparison of the RT-PCR assay with dual
      fusion fluorescence in situ hybridization showed an overall concordance of 95%.
      With this assay, we obtained a prevalence for the PAX8/PPARG rearrangement in FTC
      of 62% (13 of 21 cases), compared with a 5% prevalence (3 of 55) for other
      follicular cell-derived neoplasms. CONCLUSIONS: The introduction of this assay
      into clinical practice could provide useful information for the diagnosis and
      possibly for the prognosis and treatment of thyroid cancer in the future.

PMID- 20056740
TI  - Current approaches to pharmacotherapy for smoking cessation.
AB  - It is well established that smoking is the primary preventable cause of disease
      and death in the United States and that it is responsible for a wide range of
      negative health consequences, including but not limited to respiratory disease.
      According to the US Public Health Service, all patients attempting to quit
      smoking should be encouraged to use one or more effective pharmacotherapy agents
      for cessation except in the presence of special circumstances or in populations
      for which there is insufficient evidence of effectiveness (pregnant women,
      smokeless tobacco users, light smokers and adolescents). These medications are
      most effective when coupled with behavioral counseling interventions. This review
      article provides an overview of comprehensive (the 5 A's framework: Ask, Advise,
      Assess, Assist, Arrange) and brief (Ask, Advise, Refer) interventions for
      assisting patients with quitting, and a more detailed review of the seven first
      line pharmacological agents for smoking cessation (nicotine replacement therapy
      formulations, bupropion SR and varenicline) and combination therapy regimens.
      This information will facilitate respiratory therapists in addressing the most
      important risk factor for pulmonary disease in the patient population that they
      serve.

PMID- 20056741
TI  - Effects of MK-801, taurine and dextromethorphan on neurotoxicity caused by
      manganese in rats.
AB  - The effects of manganese on the activities of GS, PAG, SDH and Na(+)-K(+)-ATPase
      were investigated and the impact of MK-801, Tau and DM on manganese-induced
      neurotoxicity were observed in rats. Seventy Wistar rats were divided into seven
      groups, 10 animals for each group. The first group was the control group, the
      second to fourth groups were 8, 40 and 200 micromol/kg MnCl(2) groups, the fifth
      to seventh groups were 0.3 micromol/kg MK-801, 1 micromol/kg Tau and 13.5
      micromol/kg DM pretreatment groups. The animals were injected with manganese
      chloride for 25 days and pretreated for every other day. Manganese resulted in
      the reduction of GS, SDH and Na(+)-K(+)-ATPase activities, and the increase of
      PAG activity. The percentage of positive area and integral optical density of
      glutamate immunocreative cell were significantly increased in the group given 200
      micromol/kg MnCl(2) alone. Pretreatment with MK-801, Tau and DM can antagonize
      neurotoxicity induced by manganese in the certain extent.

PMID- 20056742
TI  - A CD36 synthetic peptide inhibits silica-induced lung fibrosis in the mice.
AB  - Silicosis is a kind of pneumoconiosis caused by inhalation of silica dust, which
      is characterized by lung fibrosis. The biologically active form of transforming
      growth factor-beta1 (TGF-beta1) plays a key role in the development of lung
      fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF
      beta1) to active TGF-beta1. The antagonistic effect of the synthetic peptide was
      analyzed by the administration of CD36 (93-110) synthetic peptide to the
      silicosis model of mice. The hydroxyproline content of the silica + CD36 (93-110)
      synthetic peptide group was significantly lower than that of the other
      experimental groups [silica and silica + CD36 (208-225) synthetic peptide groups]
      (p < .05). Inflammation, fibrotic degree and distribution of collagen fibers in
      silicotic nodules of the silica + CD36 (93-110) synthetic peptide group were less
      than those of the other experimental groups. The expressions of collagen I and
      III of the silica + CD36 (93-110) synthetic peptide group were significantly
      lower than those of the other experimental groups (p < .05). CD36 (93-110)
      synthetic peptide reduced the tissue fibrotic pathologies and collagen
      accumulation in the silicosis model of mice, resulting in the decreased severity
      of silica-induced lung fibrosis.

PMID- 20056743
TI  - The role of oxidative DNA damage, DNA repair, GSTM1, SOD2 and OGG1 polymorphisms
      in individual susceptibility to Barrett's esophagus.
AB  - Determination of the genetic alterations, which play a role in the etiology of
      Barrett's esophagus (BE), could help identify high-risk individuals for
      esophageal adenocarcinoma (EA). The aim of the present study was to investigate
      the role of oxidative DNA damage, glutathione (GSH) concentration as oxidative
      stress parameters and DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1
      Ser326Cys genetic polymorphisms as individual susceptibility parameters in the
      etiology of BE. The study groups comprised BE patients who were clinically
      diagnosed (n = 40) and a healthy control group (n = 40). Basal DNA damage,
      pyrimidine and purine base damage after H(2)O(2) induction, H( 2)O(2)
      sensitivity, DNA repair capacity, oxidized pyrimidine and purine base damage
      repair were evaluated in peripheral blood lymphocytes with a modified comet assay
      using specific endonucleases (Endo III and Fpg). Polymerase chain reaction
      restriction length polymorphism (PCR-RFLP)-based assays were used for genotyping.
      The patient group showed elevated levels of basal DNA damage, pyrimidine base
      damage and H(2)O(2) sensitivity as compared to controls (p < .05). DNA repair
      capacity, oxidized pyrimidine and purine base damage repair capacity, were not
      statistically different between patients and controls. GSH concentration was
      found to be significantly lower in smoking patients than in the controls (p <
      .05). None of the genetic variations changed the risk of having BE disease.
      However, patients carrying the variant OGG1 Cys allele showed elevated levels of
      pyrimidine base damage as compared to patients carrying the wild-type OGG1 Ser (p
      < .05). The results of this study point to a role of oxidative DNA damage in BE.
      However, DNA repair capacity, GSTM1, SOD1 Ala16Val and OGG1 Ser326Cys genetic
      polymorphisms appeared to play no role in the individual susceptibility to this
      disease.

PMID- 20056744
TI  - Beryllium contamination and exposure monitoring in an inhalation laboratory
      setting.
AB  - Beryllium (Be) is used in several forms: pure metal, beryllium oxide, and as an
      alloy with copper, aluminum, or nickel. Beryllium oxide, beryllium metal, and
      beryllium alloys are the main forms present in the workplace, with inhalation
      being the primary route of exposure. Cases of workers with sensitization or
      chronic beryllium disease challenge the scientific community for a better
      understanding of Be toxicity. Therefore, a toxicological inhalation study using a
      murine model was performed in our laboratory in order to identify the toxic
      effects related to different particle sizes and chemical forms of Be. This
      article attempts to provide information regarding the relative effectiveness of
      the environmental monitoring and exposure protection program that was enacted to
      protect staff (students and researchers) in this controlled animal beryllium
      inhalation exposure experiment. This includes specific attention to particle
      migration control through intensive housekeeping and systematic airborne and
      surface monitoring. Results show that the protective measures applied during this
      research have been effective. The highest airborne Be concentration in the
      laboratory was less than one-tenth of the Quebec OEL (occupational exposure
      limit) of 0.15 microg/m(3). Considering the protection factor of 10(3) of the
      powered air-purifying respirator used in this research, the average exposure
      level would be 0.03 x 10(- 4) microg/m(3), which is extremely low. Moreover, with
      the exception of one value, all average Be concentrations on surfaces were below
      the Quebec Standard guideline level of 3 microg/100 cm(2) for Be contamination.
      Finally, all beryllium lymphocyte proliferation tests for the staff were not
      higher than controls.

PMID- 20056745
TI  - Angiotensin II promotes development of the renal microcirculation through AT1
      receptors.
AB  - Pharmacologic or genetic deletion of components of the renin-angiotensin system
      leads to postnatal kidney injury, but the roles of these components in kidney
      development are unknown. To test the hypothesis that angiotensin II supports
      angiogenesis during postnatal kidney development, we quantified CD31(+)
      postglomerular microvessels, performed quantitative PCR analysis of vascular
      growth factor expression, and measured renal blood flow by magnetic resonance.
      Treating rats with the angiotensin II type 1 receptor antagonist candesartan for
      2 weeks after birth reduced the total length, volume, and surface area of
      capillaries in both the cortex and the medulla and inhibited the organization of
      vasa recta bundles. In addition, angiotensin II type 1 antagonism inhibited the
      transcription of angiogenic growth factors vascular endothelial growth factor,
      angiopoietin-1, angiopoietin-2, and the angiopoietin receptor Tie-2 in cortex and
      medulla. Similarly, Agtr1a(-/-);Agtr1b(-/-) mouse kidneys had decreased
      angiopoietin-1, angiopoietin-2, and Tie-2 mRNAs at postnatal day 14. To test
      whether increased urinary flow leads to microvascular injury, we induced
      postnatal polyuria with either lithium or adrenalectomy, but these did not alter
      vascular endothelial growth factor expression or vasa recta organization.
      Compared with vehicle-treated rats, renal blood flow was significantly
      (approximately 20%) lower in candesartan-treated rats even 14 days after
      candesartan withdrawal. Taken together, these data demonstrate that angiotensin
      II promotes postnatal expansion of postglomerular capillaries and organization of
      vasa recta bundles, which are necessary for development of normal renal blood
      flow.

PMID- 20056746
TI  - Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy.
AB  - The role of microRNAs (miRs), which are endogenous RNA oligonucleotides that
      regulate gene expression, in diabetic nephropathy is unknown. Here, we performed
      expression profiling of cultured proximal tubular cells (PTCs) under high-glucose
      and control conditions. We identified expression of 103 of 328 microRNAs but did
      not observe glucose-induced changes in expression. Next, we performed miR
      expression profiling in pooled RNA from formalin-fixed, paraffin-embedded tissue
      from renal biopsies. We studied three groups of patients with established
      diabetic nephropathy and detected 103 of 365 miRs. Two miRs differed by more than
      two-fold between progressors and nonprogressors, and 12 miRs differed between
      late presenters and other biopsies. We noted the greatest change in miR-192
      expression, which was significantly lower in late presenters. Furthermore, in
      individual biopsies, low expression of miR-192 correlated with tubulointerstitial
      fibrosis and low estimated GFR. In vitro, treatment of PTCs with TGF-beta1
      decreased miR-192 expression. Overexpression of miR-192 suppressed expression of
      the E-Box repressors ZEB1 and ZEB2, thereby opposing TGF-beta-mediated
      downregulation of E-cadherin. In summary, loss of miR-192 expression associates
      with increased fibrosis and decreased estimated GFR in diabetic nephropathy in
      vivo, perhaps by enhancing TGF-beta-mediated downregulation of E-cadherin in
      PTCs.

PMID- 20056747
TI  - High prevalence of sickle cell trait in African Americans with ESRD.
AB  - Sickle cell trait (HbAS) associates with impaired urinary concentration,
      hematuria, and renal papillary necrosis, but its prevalence among African
      Americans with ESRD is unknown. We performed a cross-sectional study reviewing
      available hemoglobin phenotypes for 188 of 206 adult African-American patients
      receiving renal replacement therapy in four dialysis units. Results from the
      state newborn screening program in corresponding counties provided the local
      population prevalence of sickle trait among African Americans. Compared with the
      general African-American population, HbAS was twice as common among African
      Americans with ESRD (15% versus 7%, P < 0.001). Prevalence of hemoglobin C trait
      (HbAC) was similarly more common (5% versus 2%, P < 0.01). The higher prevalence
      of HbAS and HbAC in the ESRD population raises the possibility that these
      hemoglobinopathies contribute to a decline in kidney function, either alone or in
      conjunction with other known risk factors for renal disease. The potential effect
      of HbAS on the development and progression of CKD and its effect on the course
      and management of patients with ESRD deserve further study.

PMID- 20056748
TI  - The microRNA-processing enzyme dicer maintains juxtaglomerular cells.
AB  - Juxtaglomerular cells are highly specialized myoepithelioid granulated cells
      located in the glomerular afferent arterioles. These cells synthesize and release
      renin, which distinguishes them from other cells. How these cells maintain their
      identity, restricted localization, and fate is unknown and is fundamental to the
      control of BP and homeostasis of fluid and electrolytes. Because microRNAs may
      control cell fate via temporal and spatial gene regulation, we generated mice
      with a conditional deletion of Dicer, the RNase III endonuclease that produces
      mature microRNAs in cells of the renin lineage. Deletion of Dicer severely
      reduced the number of juxtaglomerular cells, decreased expression of the renin
      genes (Ren1 and Ren2), lowered plasma renin concentration, and decreased BP. As a
      consequence of the disappearance of renin-producing cells, the kidneys developed
      striking vascular abnormalities and prominent striped fibrosis. We conclude that
      microRNAs maintain the renin-producing juxtaglomerular cells and the morphologic
      integrity and function of the kidney.

PMID- 20056749
TI  - GSK3beta plays dirty in acute kidney injury.

PMID- 20056750
TI  - Satellite cell dysfunction and impaired IGF-1 signaling cause CKD-induced muscle
      atrophy.
AB  - Muscle wasting in chronic kidney disease (CKD) begins with impaired insulin/IGF-1
      signaling, causing abnormal protein metabolism. In certain models of muscle
      atrophy, reduced satellite cell function contributes to atrophy, but how CKD
      affects satellite cell function is unknown. Here, we found that isolated
      satellite cells from mice with CKD had less MyoD, the master switch of satellite
      cell activation, and suppressed myotube formation compared with control mice. In
      vivo, CKD delayed the regeneration of injured muscle and decreased MyoD and
      myogenin expression, suggesting that CKD impairs proliferation and
      differentiation of satellite cells. In isolated satellite cells from control
      mice, IGF-1 increased the expression of myogenic genes through an Akt-dependent
      pathway. CKD impaired Akt phosphorylation in satellite cells after muscle injury.
      To test whether impaired IGF-1 signaling could be responsible for decreased
      satellite cell function in CKD, we created an inducible IGF-1 receptor knockout
      mouse and found impaired satellite cell function and muscle regeneration. In
      addition, both CKD and IGF-1 receptor knockout mice developed fibrosis in
      regenerating muscles. Taken together, impaired IGF-1 signaling in CKD not only
      leads to abnormal protein metabolism in muscle but also impairs satellite cell
      function and promotes fibrosis in regenerating muscle. These signaling pathways
      may hold potential therapeutic targets to reduce CKD-related muscle wasting.

PMID- 20056752
TI  - Dialysis and transplantation in Fabry disease: indications for enzyme replacement
      therapy.
AB  - ESRD is a major cause of morbidity and premature mortality in Fabry disease,
      particularly in classically affected males. The decline of renal function in
      Fabry nephropathy is adversely affected by male gender, advanced chronic kidney
      disease (CKD), and severe proteinuria. The diagnosis of Fabry nephropathy may be
      missed if not specifically addressed in progressive CKD and patients have been
      first identified in screening programs of dialysis patients. Fabry patients have
      worse 3-year survival rates on dialysis as compared with nondiabetic controls.
      The 5-year survival rate of transplanted Fabry patients is also lower than that
      of controls. However, because Fabry nephropathy does not recur in the allograft
      and transplanted Fabry patients appear to have better overall outcomes than those
      maintained on dialysis, kidney transplantation should be recommended as a first
      choice in renal replacement therapy (RRT) for Fabry disease. Appropriately
      designed and powered studies are not available to answer the question whether
      enzyme replacement therapy (ERT) influences outcomes, the course of
      cardiomyopathy, events, or survival in Fabry patients on RRT. The authors are not
      aware of compelling indications for ERT in RRT patients because progression of
      cardiomyopathy was documented during ERT. Whether the excess mortality risk of
      Fabry patients on RRT can be prevented by ERT is unknown. Despite observational
      reports of symptomatic improvement, the available evidence supporting ERT for
      such patients is not compelling enough. To clarify this issue, studies are needed
      to test the effectiveness of agalsidases in preventing cardiac and
      cerebrovascular complications in Fabry patients with ESRD.

PMID- 20056751
TI  - GSK3beta mediates renal response to vasopressin by modulating adenylate cyclase
      activity.
AB  - Glycogen synthase kinase 3beta (GSK3beta), a serine/threonine protein kinase, is
      a key target of drug discovery in several diseases, including diabetes and
      Alzheimer disease. Because lithium, a potent inhibitor of GSK3beta, causes
      nephrogenic diabetes insipidus, GSK3beta may play a crucial role in regulating
      water homeostasis. We developed renal collecting duct-specific GSK3beta knockout
      mice to determine whether deletion of GSK3beta affects arginine vasopressin
      dependent renal water reabsorption. Although only mildly polyuric under normal
      conditions, knockout mice exhibited an impaired urinary concentrating ability in
      response to water deprivation or treatment with a vasopressin analogue. The
      knockout mice had reduced levels of mRNA, protein, and membrane localization of
      the vasopressin-responsive water channel aquaporin 2 compared with wild-type
      mice. The knockout mice also expressed lower levels of pS256-AQP2, a
      phosphorylated form crucial for membrane trafficking. Levels of cAMP, a major
      regulator of aquaporin 2 expression and trafficking, were also lower in the
      knockout mice. Both GSK3beta gene deletion and pharmacologic inhibition of
      GSK3beta reduced adenylate cyclase activity. In summary, GSK3beta inactivation or
      deletion reduces aquaporin 2 expression by modulating adenylate cyclase activity
      and cAMP generation, thereby impairing responses to vasopressin in the renal
      collecting duct.

PMID- 20056753
TI  - Review on pharmacokinetics and pharmacodynamics and the aging kidney.
AB  - In people who are aged >65 years, pharmacokinetics are influenced more by the
      loss of kidney function than by the aging process of any other organ. A GFR of 30
      to 60 ml/min, suggestive of stage 3 kidney disease, is observed in 15 to 30% of
      elderly people. Drug dosing must be adjusted to both changing pharmacokinetics
      and pharmacodynamics; the pharmacodynamics might be influenced by the aging of
      other organs, too. Using our NEPharm database, we extracted abstracts with
      pharmacokinetic parameters since 1999 from a weekly PubMed search. The recorded
      data were analyzed and compared with published recommendations on drug dosage and
      use in the elderly. Purely age-related changes in pharmacokinetic parameters were
      recorded from publications on 127 drugs. The analysis of our NEPharm records
      revealed an average (mean +/- SD) age-related prolongation of half-life of 1.39
      fold (corresponding to +39 +/- 61%). Contrasting to common opinion, mean changes
      in clearance (-1 +/- 54%) and volume of distribution (+24 +/- 56%) were even
      less. The modest changes in pharmacokinetics do not suggest general dosage
      modifications in the elderly for most drugs. Changes in pharmacodynamics justify
      the common medication rule in the elderly-"start low + go slow"-especially for
      drugs that act on the central nervous system; however, in the case of anti
      infective and anticancer therapy, the rule should be "hit hard = start high + go
      fast" to produce the target effect also in the elderly.

PMID- 20056754
TI  - Outcomes associated with serum calcium level in men with non-dialysis-dependent
      chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Elevated serum calcium has been associated with
      increased mortality in dialysis patients, but it is unclear whether the same is
      true in non-dialysis-dependent (NDD) chronic kidney disease (CKD). Outcomes
      associated with low serum calcium are also not well-characterized. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: We examined associations of baseline, time
      varying, and time-averaged serum calcium with all-cause mortality in a historic
      prospective cohort of 1243 men with moderate and advanced NDD CKD by using Cox
      models. RESULTS: The association of serum calcium with mortality varied according
      to the applied statistical models. Higher baseline calcium and time-averaged
      calcium were associated with higher mortality (multivariable adjusted hazard
      ratio (95% confidence interval): 1.31 (1.13, 1.53); P < 0.001 for a baseline
      calcium 1 mg/dl higher). However, in time-varying analyses, lower calcium levels
      were associated with increased mortality. CONCLUSIONS: Higher serum calcium is
      associated with increased long-term mortality (as reflected by the baseline and
      time-averaged models), and lower serum calcium is associated with increased short
      term mortality (as reflected by the time-varying models) in patients with NDD
      CKD. Clinical trials are warranted to determine whether maintaining normal serum
      calcium can improve outcomes in these patients.

PMID- 20056755
TI  - Neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac
      surgery: the effect of baseline renal function on diagnostic performance.
AB  - BACKGROUND AND OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is
      rapidly released by renal tubules after injury, potentially allowing early
      identification of acute kidney injury (AKI) after cardiac surgery. However, the
      diagnostic performance of NGAL has varied widely in clinical studies, and it
      remains unknown what factors modify the relationship between NGAL and AKI. We
      hypothesized the relationship between urinary NGAL and AKI would vary with
      baseline renal function, allowing a stratified analysis to improve diagnostic
      performance of this novel biomarker. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We performed a prospective observational study in 426 adult cardiac
      surgical patients. Urinary NGAL was serially determined, commencing
      preoperatively and continuing 24 hours postoperatively. AKI was defined as
      increase in serum creatinine from baseline by either >50% or >0.3 mg/dl within 48
      hours postoperatively. Patients were stratified by baseline estimated GFR (eGFR).
      NGAL levels were compared between patients with and without AKI and diagnostic
      characteristics determined according to baseline eGFR. RESULTS: In patients with
      baseline eGFR >or=60 ml/min, urinary NGAL was higher at all postoperative time
      points in patients who developed AKI compared with those who did not. In patients
      with baseline eGFR <60 ml/min, urinary NGAL did not differ at any time between
      those who did and those who did not develop AKI. Postoperative NGAL best
      identified AKI in patients with baseline eGFR 90 to 120 ml/min. CONCLUSIONS: The
      relationship between urinary NGAL and AKI after cardiac surgery varies with
      baseline renal function, with optimal discriminatory performance in patients with
      normal preoperative function.

PMID- 20056756
TI  - Consensus report on therapeutic drug monitoring of mycophenolic acid in solid
      organ transplantation.
AB  - With the increasing use of mycophenolic acid (MPA) in solid organ
      transplantation, the need for more accurate drug dosing has become evident.
      Personalized immunosuppressive therapy requires better strategies for avoidance
      of drug-related toxicity while maintaining efficacy. Few studies have assessed
      the clinical usefulness of therapeutic drug monitoring (TDM) of MPA in solid
      organ transplantation in a prospective way, and they have produced opposing
      results. To provide clinicians with an objective and balanced clinical
      interpretation of the current scientific evidence on TDM of MPA, a consensus
      meeting involving 47 experts from around the world was commissioned by The
      Transplantation Society and held in Rome on November 20 to 21, 2008. The goal of
      this consensus meeting was to offer information to transplant practitioners on
      clinically relevant pharmacokinetic characteristics of MPA, to rationalize the
      basis for currently advised target exposure ranges for MPA in various types of
      organ transplantation, and to summarize available methods for application of MPA
      TDM in clinical practice. Although this consensus report does not evaluate the
      final role of MPA TDM in transplantation, it seeks to examine the current
      scientific evidence for concentration-controlled dosing of MPA.

PMID- 20056757
TI  - Effect of different dialysis modalities on microinflammatory status and
      endothelial damage.
AB  - BACKGROUND AND OBJECTIVES: We studied the relationship between microinflammation
      and endothelial damage in chronic kidney disease (CKD) patients on different
      dialysis modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Four groups
      of CKD stage 5 patients were studied: 1) 14 nondialysis CKD patients (CKD-NonD);
      2) 15 hemodialysis patients (HD); 3) 12 peritoneal dialysis patients with
      residual renal function >1 ml/min (PD-RRF >1); and 4) 13 peritoneal dialysis
      patients with residual renal function <or=1 ml/min (PD-RRF <or=1). Ten healthy
      subjects served as controls. CD14(+)CD16(+) cells and apoptotic endothelial
      microparticles (EMPs) were measured by flow cytometry. Serum vascular endothelial
      growth factor (VEGF) was measured by ELISA. RESULTS: CKD-NonD and HD patients had
      a higher percentage of CD14(+)CD16(+) monocytes than PD groups and controls.
      CD14(+)CD16(+) was similar in the PD groups, regardless of their RRF, and
      controls. The four uremic groups displayed a marked increase in apoptotic EMPs
      and VEGF compared with controls. Apoptotic EMPs and VEGF were significantly
      higher in HD patients than in CKD-NonD and both PD groups. However, there were no
      significant differences between CKD-NonD and the two PD groups. There was a
      correlation between CD14(+)CD16(+) and endothelial damage in CKD-NonD and HD
      patients, but not in PD and controls. CONCLUSIONS: There was an increase in
      CD14(+)CD16(+) only in CKD-NonD and HD patients. In these patients, there was a
      relationship between increased CD14(+)CD16(+) and endothelial damage. These
      results strongly suggest that other factors unrelated to the microinflammatory
      status mediated by CD14(+)CD16(+) are promoting the endothelial damage in PD,
      regardless of their RRF.

PMID- 20056758
TI  - Assessment of renal pathology and dysfunction in children with Fabry disease.
AB  - Overt renal disease often first presents in male individuals with Fabry disease
      in early to middle adulthood, but proteinuria and reduced GFR may occur in
      adolescents and in young children. More recently, kidney biopsy data have shown
      early renal histologic changes in pediatric patients, and kidney dysfunction,
      primarily proteinuria, seems to be more common in girls. Renal investigations and
      their timing in children remain poorly defined. A consensus on renal
      investigations is necessary to understand the natural progression of the disease
      and to evaluate the efficacy of treatments such as enzyme replacement therapies.
      This article addresses three main categories: Use of GFRs, measuring albuminuria,
      and renal biopsies in children.

PMID- 20056759
TI  - Hyponatremia independent of osteoporosis is associated with fracture occurrence.
AB  - BACKGROUND AND OBJECTIVES: Mild hyponatremia has traditionally been considered
      benign, but it may be associated with gait and attention deficits and an
      increased risk of falls that may result in fracture. A retrospective study was
      conducted to quantify the association of hyponatremia with fracture occurrence
      and to examine whether this relationship is independent of osteoporosis. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This study analyzed 1408 consecutive
      female patients who underwent bone mineral density measurement (Lunar IDXA)
      between September 1, 2006 and April 11, 2007 and who had available laboratory
      data. Self reported fracture occurrence was confirmed by radiology report or
      attendance at a fracture clinic. The significance and independence of the
      association of hyponatremia with fracture was quantified using logistic
      regression. RESULTS: The mean (SD) serum sodium ([Na(+)]) was 140.6 (3.0) mmol/L;
      59 (4.2%) had [Na(+)] < 135 mmol/L. Forty-five percent of subjects were
      osteoporotic and 18% had a prior fracture. Hyponatremia was present in 8.7% of
      those with versus 3.2% of those without a confirmed fracture (P < 0.001). On
      multivariate logistic regression analysis controlling for age, T-score, chronic
      kidney disease stage, osteoporotic risk factors (amenorrhea, family history,
      regular steroid use, smoking history, alcohol use, history of liver disease, and
      low-calcium diet), and osteoporosis treatments (calcium and vitamin D
      supplements, antiresorptives, and hormonal replacement therapy), [Na(+)] < 135
      versus [Na(+)] >or= 135 mmol/L remained significantly and independently
      associated with fracture occurrence (P < 0.01). CONCLUSIONS: Mild hyponatremia
      may be a readily identifiable and potentially modifiable risk factor for
      fracture.

PMID- 20056760
TI  - A randomized trial of cholecalciferol versus doxercalciferol for lowering
      parathyroid hormone in chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The optimal treatment of secondary hyperparathyroidism
      in chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We conducted a randomized, blinded, 3-month trial in vitamin D
      deficient CKD stage 3 and 4 patients with parathyroid hormone (PTH) values above
      the Kidney Disease Outcomes Quality Initiative target, comparing cholecalciferol
      (4000 IU/d x 1 month, then 2000 IU/d; n = 22) to doxercalciferol (1 microg/d; n =
      25). RESULTS: There was no difference in baseline demographics or lab tests,
      except a slightly higher estimated GFR (eGFR) in the doxercalciferol group. There
      was a significant increase in vitamin D level in the cholecalciferol group (14 +/
      6 to 37 +/- 10 ng/ml; P < 0.001) but no change in the doxercalciferol group. The
      PTH decreased by 27% +/- 34% in the doxercalciferol group (P = 0.002) and
      decreased by 10% +/- 31% in the cholecalciferol group (P = 0.16), but the
      difference between treatments was NS (P = 0.11). Similar results were found when
      absolute PTH change from baseline to end point was analyzed in a repeated
      measures ANOVA model. The serum calcium and urine calcium excretions were not
      different. Additional non-mineral-related end points, albuminuria, and BP were
      evaluated, and although trends were present, this did not reach significance.
      CONCLUSIONS: This prospective, randomized trial demonstrated a within-group
      reduction in PTH in the doxercalciferol-treated patients but no significant
      difference between the doxercalciferol and cholecalciferol patients. Larger, long
      term studies are needed to demonstrate efficacy of mineral-related and non
      mineral-related end points and safety.

PMID- 20056761
TI  - Rapid development of hypertension and proteinuria with cediranib, an oral
      vascular endothelial growth factor receptor inhibitor.
AB  - BACKGROUND AND OBJECTIVES: Hypertension and proteinuria are common but poorly
      understood renal toxicities of vascular endothelial growth factor (VEGF) receptor
      signaling pathway inhibitors. In this phase II study of cediranib (AZD2171) for
      recurrent epithelial ovarian cancer, the time course and severity of BP changes
      and proteinuria were characterized. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: 46 women ages 41 to 77 years were treated with cediranib. 26% had
      baseline hypertension. Twice-daily BP was recorded. Urinalyses were performed
      every 2 weeks, and in some patients proteinuria was further quantified. RESULTS:
      31 women (67%) developed hypertension by day 3; 87% by the end of the study. 43%
      developed grade > or =3 hypertension. Mean systolic BP increase over 3 days was
      18 mmHg. Women above the mean age (> or =57 years) had a larger rise in systolic
      BP by day 3 (15.9 versus 7.0 mmHg). 14 women developed proteinuria. There was a
      dose response (45 versus 30 mg daily). Proteinuria also developed rapidly, with 7
      of 14 women developing proteinuria within 2 weeks. Only 7 of 20 women who
      developed grade 3 hypertension developed proteinuria. CONCLUSIONS: Cediranib
      induced a rapid but variable rise in BP within 3 days of initiation in most
      patients. Proteinuria was common and also developed rapidly. The rapid
      development of hypertension suggests that acute inhibition of VEGF-dependent
      vasodilation might explain the BP rise with VEGF inhibitors. Clinicians must be
      vigilant in early detection and management of toxicities of this expanding drug
      class, especially in older patients.

PMID- 20056762
TI  - Cardiovascular death in dialysis patients: lessons we can learn from AURORA.
AB  - Cardiovascular events are the dominant cause of death in patients with ESRD.
      Until recently, plaque rupture due to atherogenic dyslipoproteinemias was
      presumed to be a major mechanism of cardiovascular events in dialysis patients.
      But how reasonable was that hypothesis and was it entirely discredited by the
      results of 4D and AURORA? This article places the conventional lipids-cholesterol
      and triglyceride-within the more physiologic framework of the apoB lipoproteins.
      Viewed from the perspective of atherogenic particle number, the failure of
      statins to lower cardiovascular mortality in hemodialysis patients versus the
      continuing potential for success in peritoneal dialysis patients becomes
      comprehensible. In the former, apoB is characteristically not elevated and
      therefore apoB-lowering therapy can have only limited effect; in the latter, apoB
      is characteristically high and therefore apoB-lowering therapy might have
      considerable clinical benefit. Nevertheless, plaque rupture is only one mechanism
      leading to cardiac death. In addition to those previously noted, a new mechanism
      is suggested for consideration-recurrent reperfusion injury. The coronaries of
      dialysis patients are often narrowed, the microcirculation underdeveloped, and
      the left ventricle hypertrophied-all of these plus transient hypotension could
      produce severe ischemia followed by reperfusion necrosis. The minor but common
      elevations of troponin that are so well known yet widely disregarded may be
      markers of an adverse sequence of events that could each trigger a fatal
      arrhythmia and tend to reduce left ventricular function. Thus sudden death due to
      arrhythmia and slow progressive death due to heart failure could be
      manifestations of reperfusion injury.

PMID- 20056763
TI  - Variation in fistula use across dialysis facilities: is it explained by case-mix?
AB  - BACKGROUND AND OBJECTIVES: Arteriovenous fistulas (AVFs) remain the preferred
      vascular access for hemodialysis patients. Dialysis facilities that fail to meet
      Centers for Medicare & Medicaid Services goals cite patient case-mix as a reason
      for low AVF prevalence. This study aimed to determine the magnitude of the
      variability in AVF usage across dialysis facilities and the extent to which
      patient case-mix explains it. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The
      vascular access used in 10,112 patients dialyzed at 173 Dialysis Clinic Inc.
      facilities from October 1 to December 31, 2004, was evaluated. The access in use
      was considered to be an AVF if it was used for >70% of hemodialysis treatments.
      Mixed-effects models with a random intercept for dialysis facilities evaluated
      the effect of facilities on AVF usage. Sequentially adjusted multivariate models
      measured the extent to which patient factors (case-mix) explain variation across
      facilities in AVF rates. RESULTS: 3787 patients (38%) were dialyzed using AVFs.
      There was a significant facility effect: 7.6% of variation in AVF use was
      attributable to facility. This was reduced to 7.1% after case-mix adjustment.
      There were no identified specific facility-level factors that explained the
      interfacility variation. CONCLUSIONS: AVF usage varies across dialysis
      facilities, and patient case-mix did not reduce this variation. In this study,
      92% of the total variation in AVF usage was due to patient factors, but most were
      not measurable. A combination of patient factors and process indicators should be
      considered in adjudicating facility performance for this quality indicator.

PMID- 20056764
TI  - Leukocytosis as a predictor for non-infective mortality and morbidity.
AB  - Leukocytosis (raised concentration of white cells in the blood) is commonly
      associated with infection or inflammation, but can occur in a wide variety of
      other conditions. Leukocytosis has also been linked with increased mortality and
      morbidity in a number of studies. We have systematically reviewed the relevant
      literature, which clearly demonstrates an association between leukocytosis and
      mortality-particularly due to cardiovascular or cerebrovascular causes. The
      mechanisms of this effect are uncertain but, when combined with other markers
      predictive of death, leukocytosis may contribute to modelling systems to predict
      in-patient mortality risk.

PMID- 20056765
TI  - Cohort profile: The Hunter Community Study.

PMID- 20056766
TI  - Commentary: The challenge of prevention in China.

PMID- 20056767
TI  - Pregabalin in fibromyalgia: meta-analysis of efficacy and safety from company
      clinical trial reports.
AB  - OBJECTIVES: Meta-analysis of pregabalin trials in FM using company trial reports,
      which provide more detailed information about trials than published papers. FM is
      a common condition with a significant impact on quality of life. METHODS: Reports
      of five high-quality randomized trials (3808 patients) of pregabalin in FM were
      obtained from Pfizer. Four trials (2754 patients) were of classical trial design
      and one was an enriched enrolment randomized withdrawal design. Outcomes for meta
      analysis from the four trials with classical design were pooled in an intention
      to-treat analysis. RESULTS: Significant benefit of pregabalin over placebo was
      seen for a variety of outcomes including mean pain and sleep scores, the
      proportion of patients achieving at least 50% pain relief and most of the
      individual domains of short-form 36. Only a minority of patients achieve moderate
      or substantial pain relief. The proportions of patients with any adverse event,
      somnolence or dizziness were also significantly greater with pregabalin than with
      placebo. There was no difference with regard to serious adverse events. A dose
      response relationship was apparent for at least 50% pain relief and for adverse
      event outcomes. CONCLUSIONS: Pregabalin is effective in treating FM and is
      relatively safe. The size of therapeutic effect is similar to that with other
      recent interventions such as duloxetine and the combination of tramadol and
      paracetamol. Enriched enrolment randomized withdrawal design gives similar
      results to classical trial designs in FM.

PMID- 20056768
TI  - Comment on: Sarcoid-like granulomatosis in patients treated with tumour necrosis
      factor blockers: 10 cases.

PMID- 20056769
TI  - Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an
      observational study from the British Society for Rheumatology Biologics Register.
AB  - OBJECTIVES: To evaluate the risk-benefit profile of anti-TNF therapies in PsA and
      to study the predictors of treatment response and disease remission [disease
      activity score (DAS)-28 < 2.6]. METHODS: The study included PsA patients (n =
      596) registered with the British Society for Rheumatology Biologics Register
      (BSRBR). Response was assessed using the European League against Rheumatism
      (EULAR) improvement criteria. Univariate and multivariate logistic regression
      models were developed to examine factors associated with EULAR response and
      disease remission using a range of covariates. Poisson regression was used to
      calculate incidence rate ratios (IRRs) for serious adverse events (SAEs) vs
      seronegative RA controls receiving DMARDs, adjusting for age, sex and baseline co
      morbidity. RESULTS: At baseline, the mean (s.d.) DAS-28 was 6.4 (5.6). Of the
      patients, 70.3% were EULAR responders at 12 months. At 6 months, older patients
      [adjusted odds ratio (OR) 0.97 per year; 95% CI 0.95, 0.99], females (adjusted OR
      0.51; 95% CI 0.34, 0.78) and patients on corticosteroids (adjusted OR 0.45; 95%
      CI 0.28, 0.72) were less likely to achieve a EULAR response. Over 1776.2 person
      years of follow-up (median 3.07 per person), the IRR of SAEs compared with
      controls was not increased (1.0; 0.8, 1.3) [corrected]. CONCLUSIONS: Anti-TNF
      therapies have a good response rate in PsA, and have an adverse event profile
      similar to that seen in a control cohort of patients with seronegative arthritis
      receiving DMARD therapy.

PMID- 20056771
TI  - Molecular screening for Candida orthopsilosis and Candida metapsilosis among
      Danish Candida parapsilosis group blood culture isolates: proposal of a new RFLP
      profile for differentiation.
AB  - Candida orthopsilosis and Candida metapsilosis are recently described species
      phenotypically indistinguishable from Candida parapsilosis . We evaluated
      phenotyping and molecular methods for the detection of these species among 79
      unique blood culture isolates of the C. parapsilosis group obtained during the
      years 2004-2008. The isolates were screened by PCR amplification of the secondary
      alcohol dehydrogenase-encoding gene ( SADH) followed by digestion with the
      restriction enzyme Ban I, using C. parapsilosis ATCC 22019, C. orthopsilosis ATCC
      96139 and C. metapsilosis ATCC 96144 as controls. Isolates with RFLP patterns
      distinct from C. parapsilosis were characterized by sequence analysis of the ITS1
      ITS2, 26S rRNA (D1/D2) and SADH regions. Restriction patterns for the 3 species
      with each of 610 restriction enzymes were predicted in silico using 12 available
      sequences. By PCR-RFLP of the SADH gene alone, four isolates (5.1 %) had a
      pattern identical to the C. orthopsilosis reference strain. Sequence analysis of
      SADH and ITS (internal transcribed spacer) regions identified two of these
      isolates as C. metapsilosis. These results were confirmed by creating a
      phylogenetic tree based on concatenated sequences of SADH, ITS and 26S rRNA gene
      sequence regions. Optimal differentiation between C. parapsilosis, C.
      metapsilosis and C. orthopsilosis was predicted using digestion with NlaIII,
      producing discriminatory band sizes of: 131 and 505 bp; 74, 288 and 348 bp; and
      131, 217 and 288 bp, respectively. This was confirmed using the reference strains
      and 79 clinical isolates. In conclusion, reliable discrimination was obtained by
      PCR-RFLP profile analysis of the SADH gene after digestion with NlaIII but not
      with BanI. C. metapsilosis and C. orthopsilosis are involved in a small but
      significant number of invasive infections in Denmark.

PMID- 20056772
TI  - Genotyping of Acanthamoeba isolates and clinical characteristics of patients with
      Acanthamoeba keratitis in China.
AB  - Acanthamoeba keratitis (AK) is a sight-threatening corneal infection, the
      epidemiology of which is related to the specific genotype of Acanthamoeba. In
      this study, the genotypes of 14 Acanthamoeba isolates, each from a patient with
      AK, were identified according to the highly variable DF3 region in the 18S rRNA
      gene at Shandong Eye Institute, PR China, from 2000 to 2009, and the clinical
      characteristics of these patients were analysed. All 14 amoebae were genotype T4,
      representing nine different DF3 sequence types, seven of which were newly
      identified. Cornea infestation was the main risk factor for these 14 AK patients.
      Amoebic cysts could be detected in all corneal scrapes. Corneal ulcers were
      located mainly at the corneal centre, accompanied by eye pain, and some appeared
      with a Wessely ring. Surgery was carried out on all patients. Acanthamoeba
      genotypes T4/26 and T4/27 were found to cause a more severe keratitis, whilst the
      others showed no significant differences in clinical characteristics. In
      conclusion, the majority of the keratitis-causing Acanthamoeba isolates were
      genotype T4, with Acanthamoeba genotypes T4/26 and T4/27 from PR China causing a
      more severe keratitis.

PMID- 20056773
TI  - Plasmid-borne florfenicol and ceftiofur resistance encoded by the floR and blaCMY
      2 genes in Escherichia coli isolates from diseased cattle in France.
AB  - This study was designed to determine the genetic basis of florfenicol and
      ceftiofur resistance in Escherichia coli isolates recovered from French cattle.
      In these isolates, ceftiofur resistance was conferred by bla(CMY-2) located on
      three distinct conjugative plasmids on a specific DNA fragment, ISEcp1-bla(CMY-2)
      blc- sugE. Two of the plasmids also carried the floR gene conferring resistance
      to florfenicol. The floR gene was shown to be associated with the insertion
      sequence ISCR2. Mobile elements appear to contribute to the mobilization of floR
      and bla(CMY-2) genes in E. coli. The presence of bla(CMY-2) and floR on the same
      plasmid highlights the potential risk for a co-selection of the bla(CMY-2) gene
      through the use of florfenicol in food animal production.

PMID- 20056774
TI  - Effect of serial subculturing on the genetic composition and cytotoxic activity
      of Mycobacterium tuberculosis.
AB  - Continuous subculture has been observed to produce changes in the virulence of
      micro-organisms, e.g. rabies virus, poliovirus and Mycobacterium bovis BCG. The
      latter has been used as a vaccine for tuberculosis for the last 100 years;
      however, in some instances its efficacy has been observed to be very low. In
      order to determine whether similar changes can be produced in Mycobacterium
      tuberculosis, we selected four isolates, M. tuberculosis H37Rv, a Beijing strain
      (DR-689), and two more isolates with deletion of the phospholipase C locus (plcA
      plcB-plcC ), and subjected them to serial culturing on Middlebrook 7H9 medium,
      with or without ox bile. After 100 passages, we performed RFLP-IS6110 analysis to
      determine whether genomic changes were produced. We also checked their genomic
      composition by microarray analysis. Changes in virulence were studied by
      measuring the cytotoxic effect of parental and subcultured isolates on a THP-1
      macrophage monolayer. The most visible change was the change of position of an
      IS6110 band of approximately 1400 bp to approximately 1600 bp in the Beijing
      isolate subcultured in the ox bile medium. Analysis by microarray and PCR
      confirmation did not reveal any genomic changes. Cytotoxic activity was decreased
      in the isolates at levels close to that of BCG, and more consistently in those
      subcultured in the presence of ox bile.

PMID- 20056775
TI  - Spread of community-acquired meticillin-resistant Staphylococcus aureus skin and
      soft-tissue infection within a family: implications for antibiotic therapy and
      prevention.
AB  - Outbreaks or clusters of community-acquired meticillin-resistant Staphylococcus
      aureus (CA-MRSA) within families have been reported. We describe a family cluster
      of CA-MRSA skin and soft-tissue infection where CA-MRSA was suspected because of
      recurrent infections which failed to respond to flucloxacillin. While the
      prevalence of CA-MRSA is low worldwide, CA-MRSA should be considered in certain
      circumstances depending on clinical presentation and risk assessment.
      Surveillance cultures of family contacts of patients with MRSA should be
      considered to help establish the prevalence of CA-MRSA and to inform the optimal
      choice of empiric antibiotic treatment.

PMID- 20056776
TI  - Curcumin alone and in combination with augmentin protects against pulmonary
      inflammation and acute lung injury generated during Klebsiella pneumoniae B5055
      induced lung infection in BALB/c mice.
AB  - Acute lung injuries due to acute lung infections remain a major cause of
      mortality. Thus a combination of an antibiotic and a compound with
      immunomodulatory and anti-inflammatory activities can help to overcome acute lung
      infection-induced injuries. Curcumin derived from the rhizome of turmeric has
      been used for decades and it exhibits anti-inflammatory, anti-carcinogenic,
      immunomodulatory properties by downregulation of various inflammatory mediators.
      Keeping these properties in mind, we investigated the anti-inflammatory
      properties of curcumin in a mouse model of acute inflammation by introducing
      Klebsiella pneumoniae B5055 into BALB/c mice via the intranasal route. Intranasal
      instillation of bacteria in this mouse model of acute pneumonia-induced
      inflammation resulted in a significant increase in neutrophil infiltration in the
      lungs along with increased production of various inflammatory mediators [i.e.
      malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NO), tumour necrosis
      factor (TNF)-alpha] in the lung tissue. The animals that received curcumin alone
      orally or in combination with augmentin, 15 days prior to bacterial instillation
      into the lungs via the intranasal route, showed a significant (P <0.05) decrease
      in neutrophil influx into the lungs and a significant (P <0.05) decrease in the
      production of MDA, NO, MPO activity and TNF-alpha levels. Augmentin treatment
      alone did not decrease the MDA, MPO, NO and TNF-alpha levels significantly (P
      >0.05) as compared to the control group. We therefore conclude that curcumin
      ameliorates lung inflammation induced by K. pneumoniae B5055 without
      significantly (P <0.05) decreasing the bacterial load in the lung tissue whereas
      augmentin takes care of bacterial proliferation. Hence, curcumin can be used as
      an adjunct therapy along with antibiotics as an anti-inflammatory or an
      immunomodulatory agent in the case of acute lung infection.

PMID- 20056777
TI  - Discretionary calorie intake a priority for obesity prevention: results of rapid
      participatory approaches in low-income US communities.
AB  - BACKGROUND: Since resources are limited, selecting the most promising targets for
      obesity interventions is critical. We examined the relative associations of
      physical activity, fruit and vegetable consumption and 'junk food' consumption
      with BMI and the prevalence of relevant policies in school, work, food outlets
      and health-care settings. METHODS: We conducted intercept surveys in three low
      income, high-minority California communities to assess fruit, vegetable, candy,
      cookie, salty snacks and sugar-sweetened beverage consumption and self-reported
      height, weight and physical activity. We also assessed relevant policies in
      selected worksites, schools and health-care settings through key informant
      interviews. RESULTS: Data were collected from 1826 respondents, 21 schools, 40
      worksites, 14 health-care settings and 29 food outlets. The average intake of
      salty snacks, candy, cookies and sugar-sweetened beverages was estimated at 2226
      kJ (532 kcal) daily, 88% higher than the US Department of Agriculture/Department
      of Health and Human Services guidelines recommend. Energy from these sources was
      more strongly related to BMI than reported physical activity, fruit or vegetable
      consumption. Policies to promote healthy eating and physical activity were
      limited in worksites. Fruits and vegetables were less salient than junk food in
      community food outlets. CONCLUSION: Targeting consumption of salty snacks, candy
      cookies and sugar-sweetened beverages appeared more promising than alternative
      approaches.

PMID- 20056778
TI  - The role of lysosomes in limiting drug toxicity in mice.
AB  - The distribution behavior of a drug within a cell is an important, yet often
      overlooked, variable in both activity and differential selectivity. In normal
      cells, drugs with weakly basic properties are known to be extensively
      compartmentalized in acidic organelles such as lysosomes via ion trapping.
      Several cancer cell lines have been shown to have defective acidification of
      endocytic organelles and therefore have a diminished capacity to sequester such
      lysosomotropic agents. In this study, we tested the hypothesis that the low
      lysosomal pH of normal cells plays an important role in protecting normal tissues
      from the toxic effects of lysosomotropic anticancer drugs. The influence of
      lysosomal pH status on the toxicity of inhibitors of the molecular chaperone
      Hsp90 that did or did not possess lysosomotropic properties was evaluated in
      mice. Toxicity of Hsp90 inhibitors was evaluated in normal mice and in mice
      treated with chloroquine to elevate lysosomal pH by assessing morbidity and
      utilizing biochemical assays to diagnose hepatic and renal toxicity. Toxicity of
      the lysosomotropic inhibitor 17-dimethylaminoethylamino-17-demethoxy-geldanamycin
      (17-DMAG) was significantly enhanced in mice with elevated lysosomal pH relative
      to mice with normal lysosomal pH. In contrast, elevation of lysosomal pH had no
      significant impact on toxicity of the nonlysosomotropic inhibitor geldanamycin.
      These results support the notion that the low lysosomal pH of normal cells plays
      an important role in protecting these cells from the toxic effects of anticancer
      agents with lysosomotropic properties and has implications for the
      design/selection of anticancer drugs with improved safety and differential
      selectivity.

PMID- 20056779
TI  - Oral treatment with a gamma-secretase inhibitor improves long-term potentiation
      in a mouse model of Alzheimer's disease.
AB  - The beta-amyloid peptide (Abeta) is thought to play a critical role in the
      pathophysiology of Alzheimer's disease (AD). To study the effects of Abeta on the
      brain, transgenic mouse models have been developed that express high levels of
      Abeta. These mice show some features of AD, including amyloid plaques and mild
      cognitive impairment, but not others such as progressive neurodegeneration. We
      investigated the age-dependent effects of Abeta on synaptic physiology in Tg2576
      mice that express human Abeta. We report that both basal synaptic activity and
      long-term potentiation (LTP), as measured in the CA1 region of the hippocampus,
      were compromised by 7 months of age before plaque deposition. Despite a
      persistent increase in Abeta levels with age, LTP recovered in 14-month-old mice,
      with no further loss of basal activity compared with activity measured in 7-month
      old mice. Previous work has shown that inhibitors of gamma-secretase, an enzyme
      critical for Abeta synthesis, can significantly reduce Abeta production and
      plaque formation in Tg2576 mice. Our data demonstrate that 7-month-old Tg2576
      mice treated with an orally available gamma-secretase inhibitor showed a
      significant improvement in synaptic function and plasticity within days, and the
      effect was correlated with the extent and duration of Abeta reduction. These
      results indicate that recovery from Abeta-mediated synaptotoxicity can occur
      rapidly with Abeta-lowering therapies. These findings highlight some of the
      strengths and limitations of using Abeta-overexpressing mouse models for
      Alzheimer's drug discovery.

PMID- 20056780
TI  - How does calcium-dependent intracellular regulation of voltage-dependent sodium
      current increase the sensitivity to the oxadiazine insecticide indoxacarb
      metabolite decarbomethoxylated JW062 (DCJW) in insect pacemaker neurons?
AB  - Decarbomethoxylated JW062 (DCJW), the active component of the oxadiazine
      insecticide (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4
      (trifluoromethoxy)phenyl] amino]carbonyl] indeno[1,2-e][1,3,4]oxadiazine-4a(3H)
      carboxylate (DPX-JW062) (indoxacarb), was tested on 2 inward voltage-dependent
      sodium currents (named INa1 and INa2) expressed in short-term cultured dorsal
      unpaired median neurons of the cockroach Periplaneta americana. Under whole-cell
      voltage-clamp conditions, application of DCJW resulted in a biphasic dose
      dependent inhibition of the global sodium current amplitude illustrating the
      differing sensitivity of sodium channels to DCJW. INa2 was less sensitive to DCJW
      [half-maximal inhibitory concentration (IC(50)) = 1.6 microM] compared with INa1
      (IC(50) = 1.7 nM). Although a previous study demonstrated that INa1 was regulated
      by the cAMP/protein kinase A cascade, we showed that INa2 was mainly regulated in
      an opposite way by the activation of calcium-calmodulin-dependent protein
      phosphatase 2B (PP2B) and calcium-calmodulin-dependent protein kinase II (CaM
      kinase II). Furthermore, we demonstrated that activation of CaM-kinase II by
      intracellular calcium via the calcium-calmodulin complex affected the sensitivity
      of INa2 channels to DCJW. By increasing the intracellular calcium concentration
      and/or using 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (a
      calcium chelator), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide
      hydrochloride (W7) (a calmodulin inhibitor), cyclosporine A (a PP2B inhibitor),
      and 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN
      62) (a CaM-kinase II inhibitor), we revealed that activation of CaM-kinase II was
      involved in the modulation of the voltage dependence of steady-state inactivation
      and that the CaM-kinase II pathway activated by elevation of the intracellular
      calcium concentration might render INa2 channels approximately 3000-fold more
      sensitive to DCJW. These results indicated that manipulating specific
      intracellular signaling pathways involved in the regulation of sodium channels
      might have fundamental consequences for the sensitivity of insects to
      insecticides. This finding reveals an exciting research area that could lead to
      improvement in the efficiency of insecticides.

PMID- 20056781
TI  - Healthcare reform in Lithuania: evaluation of changes in human resources and
      infrastructure.
AB  - AIMS: To evaluate the change in the healthcare indicators in major and minor
      counties of Lithuania following the healthcare reforms of 2002-5. METHODS: The
      healthcare indicators were defined in the strategy for restructuring the
      healthcare settings. There were eight supply indicators (related to human
      resources and infrastructure). Analysis was performed comparing de facto data of
      major and minor counties with planned indicators. RESULTS: 1) Human resources for
      health. The planned increase in the number of family physicians was achieved in
      both subgroups of counties, as was the percentage of population serviced by
      family physicians. The number of specialist physicians decreased in major
      counties while in minor counties it increased. The number of nurses was planned
      to decrease, however it increased. 2) Infrastructure. The number of beds in
      general and specialized hospitals as well as the number of obstetric beds
      decreased as planned. The increase in the number of day care and day surgery beds
      and in the number of nursing and long-term care beds was also achieved.
      CONCLUSIONS: During the first stage of restructuring, two out of four indicators
      related to the human resources met the goals. During the same period all four
      indicators related to the infrastructure met the goals. Two indicators have
      deviated from the plans or shifted in the opposite direction. This suggests that
      planning of these indicators should be reconsidered in further plans and
      strategies.

PMID- 20056782
TI  - Structured functional assessments in general practice increased the use of part
      time sick leave: a cluster randomised controlled trial.
AB  - AIM: A method for structured functional assessments of persons with long-term
      sick leave was implemented in a cluster randomised controlled trial in general
      practice. The aim was to analyse intervention effects on general practitioner
      (GP) sick-listing practice and patient sick leave. METHODS: 57 GPs were randomly
      assigned to an intervention or a control group. The intervention group GPs
      learned the method at a 1-day workshop including teamwork and role-playing. The
      control group GPs were requested to assess functional ability as usual during the
      8 months intervention period in 2005. Outcome measures included duration of
      patient sick leave episodes, GP prescription of part-time sick leave, active sick
      leave, and vocational rehabilitation. This data was extracted from a national
      register. RESULTS: The GPs in the intervention group prescribed part-time sick
      leave more often (p < 0.01) and active sick leave less often (p = 0.04) than the
      control group GPs during the intervention period. There was no intervention
      effect on duration of patient sick leave episodes or on GP prescription of
      vocational rehabilitation. CONCLUSIONS: Implementing structured functional
      assessments in general practice made the GPs capable to assess functional ability
      of persons with long-term sick leave in a standardised and explicit manner. The
      intervention GPs' sick-listing practice was changed as they prescribed more part
      time and less active sick leave compared to the control group GPs. As a result,
      more intervention GP patients returned to part-time work compared to control GP
      patients. No intervention effect was seen on duration of patient sick leave
      episodes or on prescription of vocational rehabilitation.

PMID- 20056783
TI  - Review article: health impact assessment developments in Sweden.
AB  - AIMS: The contextual prerequisites in a country are crucial to the implementation
      and effectiveness of health impact assessment (HIA). This article aims to show
      how the Swedish government has been working to create supportive contextual
      prerequisites for HIA. These prerequisites are described based on the following
      factors: stewardship, including public health policy, party politics and legal
      preconditions; organization, including resources and funding; and delivery, which
      is dependent on the public health culture. The aim has also been to draw
      conclusions about facilitators of and obstacles to HIA implementation. METHODS:
      The article is based on a review of relevant literature. RESULTS: Since 2000, the
      Swedish government has taken a number of initiatives to increase the application
      of public health and HIA. National agencies and all of Sweden's county
      administrative boards have received government assignments with the National
      Institute of Public Health in a supportive role. CONCLUSIONS: Some facilitators
      of HIA implementation are: utilizing existing impact assessment knowledge;
      connecting HIA with the concept of a sustainable social development; and
      awareness of the time needed to adopt complex information. Obstacles detected
      are: the lack of a mandatory law for HIA; a lack of funding; and an occasional
      lack of public health skills. The final conclusion is that the public health
      policy adopted by the Swedish Riksdag, with its overarching aim of equality in
      health and its 11 domains of objectives, has had a crucial effect as a framework
      for HIA in Sweden.

PMID- 20056784
TI  - Experiences of being diagnosed with tuberculosis among immigrants in Norway-
      factors associated with diagnostic delay: a qualitative study.
AB  - AIMS: The aim of this paper is to explore experiences of being diagnosed with
      tuberculosis (TB) among immigrants in Norway, with a view to factors associated
      with diagnostic delay. METHODS: A qualitative study was conducted among 22
      participants diagnosed with TB who originated from Somalia or Ethiopia. RESULTS:
      One-third of the participants reported less than 2 months from onset of symptoms
      to treatment were initiated. The factors associated with little delay included a
      medical history that gave suspicion of TB, presenting with typical TB symptoms,
      or being screened for TB at arrival. Two-thirds of the participants told about
      extensive diagnostic processes. Persistent cough not accompanied by symptoms such
      as: weight loss and weakness; mild, diffuse, atypical, and/or intermittent
      symptoms; and a sense of not being a likely victim of TB could delay patients'
      first initiative to seek help. Participants experienced that the diagnostic
      process in the health services could endure for months, even years. The diagnosis
      could be difficult to confirm, but health professionals appeared to have
      difficulties with associating their symptoms with TB. This resulted in delays in
      initiating diagnostic tests for TB, especially in cases of extra-pulmonary TB.
      CONCLUSIONS: Public health efforts to increase awareness about TB transmission,
      its diversity in manifestations, and its progression from latent to active
      disease, may decrease patient delay. An increased awareness among health
      professionals about typical and atypical symptoms of TB, aspects of the patient's
      history, and being aware and sensitive to patients' own interpretation of
      symptoms may reduce diagnostic delay in the health services.

PMID- 20056785
TI  - How are homeless people treated in the healthcare system and other societal
      institutions? Study of their experiences and trust.
AB  - AIMS: To elucidate the perceived treatment that the homeless have received from
      the healthcare and other societal organisations and to present homeless persons'
      trust in the healthcare system and suggestions of necessary changes for improving
      it. METHODS: Homeless individuals in special houses and institutions in the
      County of Stockholm were asked to answer a short version of a public health
      survey, including added questions about how they experienced the healthcare
      providers' attitudes towards them and how much trust they had in the healthcare
      system. A total of 155 homeless persons (123 male and 32 female) were
      interviewed. RESULTS: Three-quarters of the participants stated that they had
      fairly or very high trust in healthcare services and also felt that they had been
      fairly or very well treated. Fewer females than males reported being treated well
      and they declared a lower degree of trust in the healthcare system. The homeless
      suggest that extra resources be set aside to organise their healthcare, including
      a higher level of knowledge of the medical problems prevailing in the group.
      Those who felt badly treated also asked for less neglect and disrespect from the
      healthcare staff. CONCLUSIONS: Even though a majority experience that they are
      being well treated within the healthcare system, the study also indicated
      disadvantages in the treatment of homeless persons in Sweden. The study also
      reveals an imbalance between the official ethical framework in Sweden and of the
      specific moral of some individual healthcare providers. One way to facilitate
      their entry into the healthcare system might be to create special surgeries for
      the homeless.

PMID- 20056786
TI  - Determinants of return to work after long-term sickness absence in six Danish
      municipalities.
AB  - BACKGROUND: Different follow-up times and methods in return to work (RTW)
      research make it difficult to compare results between studies, and not all
      intervention effects and determinants may be constant over time. AIMS: This study
      aimed to describe the RTW process of a population of long-term sickness-absent
      workers over a 3-year period in terms of the effect of selected determinants over
      time. METHODS: A total of 7780 sickness-absent persons were registered by social
      workers in six different municipalities and were followed up for 2 to 3 years.
      Estimates from multiple logistic regression analyses conducted for every 4 weeks
      were plotted against time to identify changes in the effects of selected
      determinants. RESULTS: After 1.5 years, 55.2% of the population had returned to
      work and this level was maintained through the remaining follow-up period. All
      the included potential determinants were found to be significantly related to RTW
      at 1 and 3 years. The effects of sex, ethnicity, and income were found to be
      nearly constant over time. The effects of municipality, diagnosis, and age
      changed markedly over time and mostly during the first year. CONCLUSIONS: RTW
      increased during the first 1.5 years after which a steady level was maintained.
      The effect of diagnosis, age, and municipality changed markedly over time.

PMID- 20056787
TI  - The social context of drunkenness in mid-adolescence.
AB  - AIMS: The aim of the study was to assess sociodemographic, parental and peer
      predictors of self-reported drunkenness in mid-adolescence. METHODS: The data
      were obtained from a national school survey covering a random half of all
      Icelandic 9th and 10th grade students (mean age 14.7 years). The overall response
      rate was 92% (n = 3,913). RESULTS: 30% of the respondents reported having been
      drunk or intoxicated at least once during the 30-day period prior to the survey.
      Multivariate logistic regression analysis showed that living with a single
      father, or in an urban area; having friends who get drunk or accept drunkenness;
      being supported by friends; having a father who gets drunk; having parents who
      assent to drunkenness; and lacking support from parents, were significantly
      associated with drunkenness. The strongest predictors of drunkenness were
      drunkenness among friends and friends' acceptance of drinking. The study did not
      find significant differences in the odds of drunkenness by gender or parental
      education. Students in 10th grade had higher odds of drunkeness than 9th grade
      students, which was accounted for by different family and peer contexts of
      younger and older adolescents. CONCLUSIONS: Residence, family structure, high
      peer support, peer acceptance, peer drunkenness, parental acceptance, father
      drunkenness, and low parental support was related to higher odds of drunkenness
      in mid-adolescents. The results give directions to future research and
      interventions intended to prevent alcohol abuse in this population.

PMID- 20056788
TI  - Comparison of socioeconomic differences in self-perceived health in Estonia and
      Finland.
AB  - AIM: To compare self-perceived health in relation to socioeconomic factors in
      Estonia and Finland. METHODS: This study was based on the 25-69 year old adult
      population of the European Social Survey, conducted in Estonia and in Finland in
      2006. Self-perceived health was rated on the five-point scale as very good, good,
      fair, poor, and very poor. The socioeconomic position was measured by the level
      of education, economic activity, and self-rated financial situation. Logistic
      regression analysis was applied to assess the association between self-perceived
      health and the socioeconomic factors. RESULTS: The prevalence of less-than-good
      health was significantly higher in Estonia than in Finland. Significant
      associations with less-than-good self-perceived health were found for less
      educated, economically non-active respondents with poorer self-rated financial
      situation in both countries. After adjustment, economic non-activity among women
      and self-rated financial situation among men appeared not to be associated with
      less-than-good self-perceived health in Finland. CONCLUSIONS: Self-perceived
      health was poorer in Estonia than in Finland, but Estonia shares with Finland a
      similar socioeconomic pattern of health. Further research is needed to monitor
      socioeconomic variations in health behaviour and mortality in both countries.

PMID- 20056789
TI  - Very long-term eradication of minimal residual disease in patients with hairy
      cell leukemia after a single course of cladribine.
AB  - Cladribine induces protracted remissions in patients with hairy cell leukemia
      (HCL). However, many long-term responders ultimately relapse. We sought to
      determine whether long-term complete responders subsequent to a single 7-day
      course of cladribine were without minimal residual disease (MRD) and potentially
      cured of HCL. From the 358-person Scripps Clinic cladribine database, we
      identified 19 patients in continuous and complete hematologic response (median
      age, 75 years; median time from diagnosis, 18 years; and median time from
      cladribine, 16 years). Nine of 19 (47%) patient samples had no evidence of
      residual disease; 7 of 19 (37%) samples had MRD; and 3 of 19 (16%) had
      morphologic evidence of HCL in hematoxylin and eosin-stained bone marrow
      sections. These results indicate that HCL is potentially curable after cladribine
      treatment. In addition, patients with MRD and even gross morphologic disease can
      live many years without manifesting hematologic relapses.

PMID- 20056790
TI  - High-throughput cell transplantation establishes that tumor-initiating cells are
      abundant in zebrafish T-cell acute lymphoblastic leukemia.
AB  - Self-renewal is a feature of cancer and can be assessed by cell transplantation
      into immune-compromised or immune-matched animals. However, studies in zebrafish
      have been severely limited by lack of these reagents. Here, Myc-induced T-cell
      acute lymphoblastic leukemias (T-ALLs) have been made in syngeneic, clonal
      zebrafish and can be transplanted into sibling animals without the need for
      immune suppression. These studies show that self-renewing cells are abundant in T
      ALL and comprise 0.1% to 15.9% of the T-ALL mass. Large-scale single-cell
      transplantation experiments established that T-ALLs can be initiated from a
      single cell and that leukemias exhibit wide differences in tumor-initiating
      potential. T-ALLs also can be introduced into clonal-outcrossed animals, and T
      ALLs arising in mixed genetic backgrounds can be transplanted into clonal
      recipients without the need for major histocompatibility complex matching.
      Finally, high-throughput imaging methods are described that allow large numbers
      of fluorescent transgenic animals to be imaged simultaneously, facilitating the
      rapid screening of engrafted animals. Our experiments highlight the large numbers
      of zebrafish that can be experimentally assessed by cell transplantation and
      establish new high-throughput methods to functionally interrogate gene pathways
      involved in cancer self-renewal.

PMID- 20056791
TI  - Prolonged activity of factor IX as a monomeric Fc fusion protein.
AB  - Treatment of hemophilia B requires frequent infusions of factor IX (FIX) to
      prophylax against bleeding episodes. Hemophilia B management would benefit from a
      FIX protein with an extended half-life. A recombinant fusion protein (rFIXFc)
      containing a single FIX molecule attached to the Fc region of immunoglobulin G
      was administered intravenously and found to have an extended half-life, compared
      with recombinant FIX (rFIX) in normal mice, rats, monkeys, and FIX-deficient mice
      and dogs. Recombinant FIXFc protein concentration was determined in all species,
      and rFIXFc activity was measured in FIX-deficient animals. The half-life of
      rFIXFc was approximately 3- to 4-fold longer than that of rFIX in all species. In
      contrast, in mice in which the neonatal Fc receptor (FcRn) was deleted, the half
      life of rFIXFc was similar to rFIX, confirming the increased circulatory time was
      due to protection of the rFIXFc via the Fc/FcRn interaction. Whole blood clotting
      time in FIX-deficient mice was corrected through 144 hours for rFIXFc, compared
      with 72 hours for rFIX; similar results were observed in FIX-deficient dogs.
      Taken together, these studies show the enhanced pharmacodynamic and
      pharmacokinetic properties of the rFIXFc fusion protein and provide the basis for
      evaluating rFIXFc in patients with hemophilia B.

PMID- 20056792
TI  - Toll-like receptor 2/6 stimulation promotes angiogenesis via GM-CSF as a
      potential strategy for immune defense and tissue regeneration.
AB  - Toll-like receptors (TLRs) are known primarily as pathogen recognition receptors
      of the innate immunity, initiating inflammatory pathways to organize the immune
      defense. More recently, an involvement of TLRs in various physiologic and
      pathologic processes has been reported. Because many of these processes implicate
      angiogenesis, we here elucidated the role of a TLR2/6-dependent pathway on
      angiogenesis using the TLR2/6 agonist macrophage-activating lipopeptide of 2 kDa
      (MALP-2), a common bacterial lipopeptide. In vivo and in vitro Matrigel assays
      demonstrated that MALP-2 promoted angiogenesis in a TLR2/6-dependent manner.
      Moreover, MALP-2 induced endothelial cell proliferation and migration and a
      strong secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM
      CSF release in response to MALP-2 from isolated vascular segments was completely
      prevented when the endothelium was removed. MALP-2 containing Matrigel implants
      exhibited vascular structures as well as CD45(+) cells. MALP-2 induced migration
      of leukocytes and likewise GM-CSF release, particularly from the monocyte
      population. Inhibition of GM-CSF by siRNA or antibodies suppressed MALP-2-induced
      angiogenesis in vitro and in vivo. These results clearly identified a TLR2/6
      dependent induction of angiogenesis by the bacterial lipopeptide MALP-2, which is
      mediated by GM-CSF. This might represent a general mechanism to enhance or
      restore blood flow and recruit immune cells for pathogen defense and tissue
      regeneration.

PMID- 20056793
TI  - Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific
      loss of band 3 and adducin in alpha-spectrin-deficient red cells.
AB  - Five spontaneous, allelic mutations in the alpha-spectrin gene, Spna1, have been
      identified in mice (spherocytosis [sph], sph(1J), sph(2J), sph(2BC), sph(Dem)).
      All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals
      previously unknown consequences of red blood cell (RBC) spectrin deficiency. In
      sph(3J), a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice
      site resulting in premature termination of translation. In sph(Ihj), a premature
      stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly
      reduced RBC membrane spectrin content, decreased band 3, and absent beta-adducin.
      Reevaluation of available, previously described sph alleles reveals band 3 and
      adducin deficiency as well. In sph(4J), a missense mutation occurs in the C
      terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia
      occurs despite minimally decreased membrane spectrin with normal band 3 levels
      and present, although reduced, beta-adducin. The severity of anemia in sph(4J)
      indicates that the highly conserved cysteine residue at the C-terminus of alpha
      spectrin participates in interactions critical to membrane stability. The data
      reinforce the notion that a membrane bridge in addition to the classic protein
      4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves
      interactions between spectrin, adducin, and band 3.

PMID- 20056795
TI  - Platelets: yin and yang.

PMID- 20056794
TI  - Prevalence and prognostic significance of KIT mutations in pediatric patients
      with core binding factor AML enrolled on serial pediatric cooperative trials for
      de novo AML.
AB  - KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in
      adults with core binding factor (CBF) acute myeloid leukemia (AML). However,
      their prevalence and prognostic significance in pediatric CBF AML is not well
      established. We performed KIT mutational analysis (exon 8 and exon 17) on
      diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4
      pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI,
      14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved
      exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI,
      0%-14%) involved both locations. Patients with KIT mutations had a 5-year event
      free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild
      type KIT (P = .86). Rates of complete remission, overall survival, disease-free
      survival, or relapse were not significantly different for patients with or
      without KIT mutations. Location of the KIT mutation and analysis by cytogenetic
      subtype [t(8;21) vs inv(16)] also lacked prognostic significance. Our study shows
      that KIT mutations lack prognostic significance in a large series of pediatric
      patients with CBF AML. This finding, which differs from adult series and a
      previously published pediatric study, may reflect variations in therapeutic
      approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies
      included in this analysis are registered at http://clinicaltrials.gov as
      NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).

PMID- 20056796
TI  - Platelet RNA chips dip into thrombocytosis.

PMID- 20056797
TI  - A role for lymphotoxin in GVHD and GVL.

PMID- 20056798
TI  - WHO subvariants of indolent mastocytosis: clinical details and prognostic
      evaluation in 159 consecutive adults.

PMID- 20056799
TI  - Both permissive and nonpermissive HLA-DPB1 mismatches can induce polyclonal HLA
      DPB1 specific immune responses in vivo and in vitro.

PMID- 20056800
TI  - Inability to achieve a therapeutic INR value while on concurrent warfarin and
      rifampin.

PMID- 20056801
TI  - Antipsychotic polypharmacy in outpatients at Birch Hill Hospital: incidence and
      adherence to guidelines.
AB  - The purpose of this article is to determine prescribing rates and adherence to
      guidelines with regard to antipsychotic polypharmacy, high-dose prescribing, and
      sedative use in an outpatient population. A prospective case-note audit involving
      250 consecutive attendees of an outpatient clinic was carried out. Data were
      analyzed using descriptive statistical methods. Differences between the groups
      were estimated using t test and chi(2) where applicable. Results showed that the
      rate of polypharmacy was 17.4%. Reasons for polypharmacy were documented in 53%
      of cases. High-dose antipsychotics were used in 2.5% of the monotherapy group and
      in 38% of the polypharmacy group. An ECG was done in 35% of patients on high-dose
      antipsychotic therapy. In the monotherapy group, 6.2% versus 26.5% in the
      polypharmacy group of patients were on at least 1 sedative or hypnotic (odds
      ratio [OR], 5.47; 95% confidence interval [CI], 2.02-14.82; P < .001). Forty-two
      percent of patients prescribed sedatives had schizophrenia spectrum disorders,
      and none of the patients were diagnosed with anxiety disorders. The current study
      confirms that despite repeated recommendations against the practice, polypharmacy
      rates remain consistent at the 20% level. Thorough documentation, calculating the
      total antipsychotic dose, and obtaining an ECG would constitute good practice.

PMID- 20056802
TI  - Acute effects of atorvastatin on glomerular filtration rate, tubular function,
      blood pressure, and vasoactive hormones in patients with type 2 diabetes.
AB  - Statins improve cardiovascular survival in both nondiabetic and diabetic
      patients, but diabetic patients benefit more, in both primary and secondary
      prevention. Statins seem to have multiple effects beyond cholesterol lowering,
      that is, pleiotropic effects that may include changes in renal function. This
      study tests the hypothesis that acute treatment with atorvastatin may change
      glomerular filtration rate, tubular function, vasoactive hormones, blood
      pressure, and pulse rate in patients with type 2 diabetes. In an acute,
      randomized, placebo-controlled, double-blinded, crossover trial, the effects of
      atorvastatin on renal function, vasoactive hormones, blood pressure, and pulse
      rate are measured in 21 patients with type 2 diabetes. Patients are randomized to
      either 2 doses of atorvastatin 80 mg or placebo before 2 different study days.
      Treatment with atorvastatin induces a significant reduction in fractional sodium
      excretion compared with placebo, and sodium clearance tends to be reduced. No
      significant differences in glomerular filtration rate, albumin/creatinine ratio,
      vasoactive hormones, and blood pressure by acute treatment with atorvastatin are
      found in diabetic patients. Acute treatment with atorvastatin reduces renal
      fractional sodium excretion in patients with type 2 diabetes. No changes are
      measured in glomerular filtration rate, albumin/creatinine ratio, vasoactive
      hormones, and blood pressure.

PMID- 20056803
TI  - Single-dose pharmacokinetics and pharmacodynamics of sergliflozin etabonate, a
      novel inhibitor of glucose reabsorption, in healthy volunteers and patients with
      type 2 diabetes mellitus.
AB  - Sergliflozin, the active entity of sergliflozin etabonate, is a selective
      inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The
      pharmacokinetics and pharmacodynamics of sergliflozin were evaluated following
      single oral dose administration of sergliflozin etabonate (5-500 mg) in healthy
      volunteers (n = 22) and patients with type 2 diabetes mellitus (n = 8). The
      prodrug was rapidly and extensively converted to sergliflozin; the latter
      displayed linear kinetics, reached maximum plasma concentrations at approximately
      30 to 45 minutes postdose (t(max)), and had a plasma elimination half-life
      (t(1/2)) of approximately 0.5 to 1 hour. Both prodrug and active entity showed
      low glomerular filtration and/or extensive renal tubular reabsorption, with <0.5%
      of the administered dose being recovered in the urine. In both populations,
      sergliflozin etabonate produced a dose-related glucosuria under fasting
      conditions and following glucose loading but did not appreciably affect urinary
      electrolyte excretion or fluid balance. The magnitude and duration of the
      glucosuric effect closely paralleled plasma sergliflozin concentrations.
      Sergliflozin did not significantly affect fasting plasma glucose levels but
      produced transient attenuation of the plasma glucose AUC following glucose
      challenge. Single doses of sergliflozin etabonate 5 to 500 mg were well
      tolerated, and there were no clinically significant adverse laboratory findings.

PMID- 20056804
TI  - Modeling the effectiveness of paliperidone ER and olanzapine in schizophrenia:
      meta-analysis of 3 randomized, controlled clinical trials.
AB  - The time course of Positive and Negative Syndrome Scale (PANSS) scores in adult
      schizophrenia patients was modeled, and the effectiveness of paliperidone
      extended-release tablets (paliperidone ER) and olanzapine was quantified. Data
      from 3 randomized, double-blind phase III studies were used. Patients received
      paliperidone ER (3, 6, 9, 12, or 15 mg), olanzapine 10 mg, or matched placebo
      once daily for 6 consecutive weeks. An indirect response model implemented using
      a nonlinear mixed effects approach described the time course of the PANSS.
      Deterioration rate was modeled as a function of baseline PANSS score, placebo,
      and drug effects, and the dropout effect. An exponential decrease of the placebo
      response was also implemented. Paliperidone ER and olanzapine treatment were
      characterized by a long-lasting drug effect (13%), with a larger but short
      lasting placebo effect (40%) and a notable dropout rate. The covariate
      exploration failed to identify any clinically relevant factors. The nonparametric
      bootstrap analysis confirmed the acceptable precision of parameter estimates. The
      visual predictive check supported the model's adequacy to reproduce observed
      PANSS time courses. The population model describes the time course of PANSS
      scores in schizophrenia patients and is appropriate for use in clinical trial
      simulation activities.

PMID- 20056805
TI  - A new editor-in-chief at the Helm!

PMID- 20056806
TI  - Update in male osteoporosis.
AB  - CONTEXT: Osteoporosis in men is becoming an increasingly important public health
      problem. One in five men over the age of 50 yr will suffer an osteoporotic
      fracture during their lifetime, and men who sustain fractures have an increased
      mortality risk. EVIDENCE ACQUISITION: Evidence was obtained by PubMed search and
      author's knowledge of the field. EVIDENCE SYNTHESIS: Studies using computed
      quantitative tomography and high-resolution peripheral computed quantitative
      tomography have provided new insights into the bone structural changes with aging
      in men, including the somewhat surprising demonstration of significant, ongoing
      trabecular bone loss starting in young adult life. In addition, there are now
      data demonstrating that serum estradiol levels are important predictors of
      fracture risk in men and that there is a threshold estradiol level below which
      not only bone loss but also fracture risk increases markedly. Criteria for
      diagnosing and managing osteoporosis in men are also evolving, including the
      application of the fracture risk assessment tool to derive 10-yr fracture risks
      in men. Three bisphosphonates (alendronate, risedronate, and zolendronic acid)
      and teriparatide are currently U.S. Food and Drug Administration approved for the
      treatment of osteoporosis in men, with a number of new compounds, including a
      monoclonal antibody against receptor activator of nuclear factor-kappaB ligand,
      selective estrogen receptor modulators, and selective androgen receptor
      modulators in varying stages of development. CONCLUSIONS: Despite significant
      advances, there remain a number of key unresolved issues regarding the
      pathogenesis and management of male osteoporosis, not the least of which is
      increasing public awareness of this important cause of morbidity and mortality in
      men.

PMID- 20056807
TI  - Necrotizing fasciitis of the back musculature as a complication of acquired
      perforating collagenosis in diabetes mellitus.

PMID- 20056808
TI  - Growth hormone post-marketing surveillance: safety, sales, and the unfinished
      task ahead.

PMID- 20056809
TI  - The exon-3 deletion of the growth hormone receptor (GHR) gene still has a limited
      impact in clinical endocrinology.

PMID- 20056810
TI  - Selectively targeting mutant BRAF in thyroid cancer.

PMID- 20056811
TI  - The thyrocyte-fibrocyte link: closing the loop in the pathogenesis of Graves'
      disease?

PMID- 20056812
TI  - Rehabilitation of older adults with hearing impairment: a critical review.
AB  - OBJECTIVE: Hearing impairment, which affects both peripheral and central
      structures of the auditory system, is highly prevalent among older adults and has
      serious consequences both for the people with hearing impairment and for those
      around them. This article provides an updated overview of the rehabilitation of
      this population. METHODS: This article critically reviews the rehabilitation
      interventions available to older adults with hearing impairment: hearing aids,
      hearing assistance technology, and communication programs. RESULTS: Current
      evidence suggests positive outcomes of similar magnitude for the three
      rehabilitation interventions, however their availability/uptake and adherence are
      suboptimal. DISCUSSION: To improve the current situation, two changes to practice
      are warranted. First, availability of the range of rehabilitation interventions
      should be improved. Second, in accordance with the self-management of other
      chronic health conditions, older adults with hearing impairment should be invited
      to be actively involved in their rehabilitation.

PMID- 20056813
TI  - Urban neighborhood context and mortality in late life.
AB  - OBJECTIVE: To examine the contextual effects of urban neighborhood
      characteristics on mortality among older adults. METHOD: Data are from the Study
      of Assets and Health Dynamics Among the Oldest Old (AHEAD). Death is assessed
      between the baseline assessment (1993) and the first follow-up interview (1995).
      Neighborhood data are from the 1990 Census. RESULTS: The log odds of dying
      between the two time points are higher in high proportion Hispanic neighborhoods,
      net of individual-level sociodemographic variables, but this effect is partly
      mediated by individual-level health. The log odds of dying are significantly (p <
      .05) lower in affluent neighborhoods, controlling for all individual-level
      variables and neighborhood proportion Hispanic. DISCUSSION: There are survival
      related benefits of living in an affluent urban neighborhood, which we posit may
      be manifested through the diffusion of innovations in health care and health
      promotion activities.

PMID- 20056814
TI  - Coronary heart disease from a life-course approach: findings from the health and
      retirement study, 1998-2004.
AB  - OBJECTIVE: Guided by a life-course approach to chronic disease, this study
      examined the ways in which childhood deprivation (low parental education and
      father's manual occupation) may be associated with coronary heart disease (CHD).
      METHOD: Multilevel modeling techniques and a nationally representative sample of
      Americans above age 50 from the Health and Retirement Study (HRS; N = 18,465)
      were used to examine childhood and CHD relationships over the course of 6 years
      (1998-2004). RESULTS: Having a father with </=8 years of education was associated
      with 11% higher odds of CHD, accounting for demographic characteristics, adult
      socioeconomic status (SES; education, income, and wealth), CHD risks (diabetes,
      hypertension, cigarette smoking, and obesity), and other factors (childhood
      health, exercise, stroke, and marital status). DISCUSSION: Policies and programs
      aimed at improving the conditions of poor children and their families may
      effectively reduce the prevalence of CHD in later life.

PMID- 20056815
TI  - Prevalence of intimate partner violence reported by homeless youth in Columbus,
      Ohio.
AB  - No study to date has reported intimate partner violence (IPV) experiences among
      homeless youth. This study sought to uncover lifetime prevalence estimates of
      physical, sexual, and emotional IPV among a nonprobability sample of 180 homeless
      male and female youth in Columbus, Ohio. To that aim, self-reported IPV and the
      association between IPV and gender, race, age, and history of childhood abuse
      were examined. Results showed that physical violence and verbal abuse were the
      most commonly reported experiences of IPV in the current sample and ranged from
      30.0% to 35.4%. Women and those with a history of childhood abuse were more
      likely to be victimized by their intimate partners. Specifically, multiple
      logistic regression analysis revealed that women were approximately twice as
      likely as men to be verbally and physically abused in intimate relationships.
      Moreover, youth who reported being victims of abuse in childhood were more than
      twice as likely to experience verbal abuse and physical violence in their
      relationships. Given the high lifetime occurrence of IPV among homeless youth,
      intervention efforts should target IPV to prevent future occurrence. Findings
      also suggest that intervention efforts should consider gender and history of
      childhood abuse.

PMID- 20056816
TI  - "But there's a million jokes about everybody . . .": prevalence of, and reasons
      for, directing negative behaviors toward gay men on a Canadian university campus.
AB  - The purpose of this study was to assess the frequency and types of negative
      behaviors directed toward gay men on university campuses and to understand
      heterosexual men's and women's motivations for engaging in antigay
      discrimination. Using a mixed methods approach, results from a quantitative
      survey (N = 286) indicated that students primarily engaged in covert antigay
      behaviors, such as telling antigay jokes and spreading gossip about gay men.
      Follow-up qualitative interviews with 8 highly homonegative individuals (4 men, 4
      women) were then conducted to better understand their self-perceived motivations
      for perpetrating antigay discrimination. Results indicated that antigay behaviors
      were conducted to reinforce traditional male gender roles, alleviate feelings of
      discomfort, and convey heterosexual identity. Participants also expressed concern
      about being perceived as prejudiced and were motivated to control their
      prejudicial reactions to some degree. Implications regarding the contemporary
      nature of antigay violence on university campuses are discussed.

PMID- 20056817
TI  - Outcomes of parental use of psychological aggression on children: a structural
      model from Sri Lanka.
AB  - The objective of this study was to explore the existence and, if so, the nature
      of the association between parental use of psychological aggression and
      psychological maladjustment in a 12-year-old Sri Lankan school population. A
      stratified random sampling technique was used to select 1,226 children from
      Colombo district schools. Three instruments, validated in the Sri Lankan context,
      were used to collect data on children's experience of psychological aggression,
      its psychological outcomes, and psychosocial correlates. The annual prevalence of
      psychological aggression reported by the study sample was 75%. A predictive model
      for psychological outcomes was examined. The experience of psychological
      aggression was shown to be moderately, but directly and significantly, associated
      with psychological maladjustment in children. This association was mediated by
      non-parentto-child violence-the child's knowledge of violence between the
      parents, experience of teacher violence, exposure to peer violence, and violence
      in the child's community. However, the child's report of a nurturant parent-child
      relationship did not impact on the association between psychological aggression
      and psychological maladjustment. The study also indicated that greater the
      child's experience of non-parent-to-child violence, the greater is his/her own
      level of hostility and aggression. These findings show that although many Sri
      Lankan parents use psychological aggression it has negative consequences for
      their children.

PMID- 20056818
TI  - Factors affecting women's response choices to dating and social situations.
AB  - This study evaluated the effects of a sexual victimization history, trait
      disinhibition, alcohol use history, number of lifetime sexual partners, and the
      contextual features of dating and social events (i.e., sexual activity and
      alcohol use) on women's response choices to a set of vignettes describing diverse
      social situations. A total of 170 undergraduate women chose one of six responses
      to each situation that varied in their degree of response refusal. Averaged
      across the situations, more severely victimized women and women reporting higher
      disinhibition chose responses lower in refusal than nonvictimized women and women
      reporting lower disinhibition. Past victimization, disinhibition, and number of
      sexual partners also moderated the influence of the situations' contextual
      features on women's response refusal. Specifically, as the presence of sexual
      activity increased in the situations, the response refusal of more severely
      victimized women increased less than nonvictimized women. In addition, as the
      presence of alcohol increased in the situations, the response refusal of women
      reporting higher disinhibition and a greater number of sexual partners decreased
      more than women reporting lower disinhibition and a fewer number of sexual
      partners.

PMID- 20056819
TI  - The roles of victim and offender substance use in sexual assault outcomes.
AB  - The impact of victim and offender preassault substance use on the outcomes of
      sexual assault incidents was analyzed. Nine hundred and seventy female sexual
      assault victims were identified from the first wave of a longitudinal study based
      on a convenience sampling strategy. Multivariate models showed that victim injury
      was more likely in assaults involving offender substance use (regardless of
      whether or not the victim was also using substances). Offender use of physical
      force and verbal threats were also related to greater odds of completed rape and
      injury, and force was associated with medical attention seeking. Based on this
      study, rape prevention programs should target men and focus on the role of
      substance use in sexual assault. These prevention programs should incorporate
      information on the roles of offender and victim substance use, offender
      aggression, and other situational factors in sexual assault outcomes. Study
      limitations and suggestions for future research on the role of victim and
      offender substance use in rape incidents are presented.

PMID- 20056820
TI  - Sensitivity of cardiac carnitine palmitoyltransferase to malonyl-CoA is regulated
      by leptin: similarities with a model of endogenous hyperleptinemia.
AB  - Acute leptin increase as well as endogenous hyperleptinemia evoked by high-fat
      diets (HF) activate fatty acid metabolism in nonadipose tissues. This supports
      the notion that hyperleptinemia is pivotal to prevent/delay steatosis during
      periods of positive energy balance. We have previously shown that long-term HF
      spares ectopic accumulation of lipids specifically in the miocardium. Because
      carnitine palmitoyltransferase I (CPT-I) allows mitochondrial uptake/oxidation of
      fatty acids, we have hypothesized that leptin drives cardiac CPT-I activity. In
      the current study, hyperleptinemia was induced in C57BL/6J mice either by
      exogenous leptin administration or by means of HF, and the ability of malonyl
      coenzyme A (malonyl-CoA) (the main endogenous inhibitor of CPT-I) to inhibit
      cardiac CPT was analyzed. IC(50) values of malonyl-CoA were 8.1 +/- 1.5
      micromol/liter in controls vs. 69.3 +/- 5.2 micromol/liter (P < 0.01) in leptin
      treated mice. This effect was also observed in cardiac explants incubated with
      leptin and was blocked by triciribine, a compound shown to inhibit protein kinase
      B (Akt) phosphorylation (pAkt). In accordance, acute leptin evoked an increase of
      cardiac pAkt levels, which correlated with CPT sensitivity to malonyl-CoA.
      Otherwise, the inhibitory effect of malonyl-CoA was hindered in HF
      hyperleptinemic mice, and in this case, pAkt levels also correlated with CPT
      sensitivity to malonyl-CoA. Our data show that leptin reduces the sensitivity of
      cardiac CPT-I to malonyl-CoA and suggest the involvement of an Akt-related
      signaling pathway in this effect. This mechanism appears to be sensitive to both
      acute and chronic hyperleptinemia. We conclude that this action of leptin is
      pivotal to drive cardiac metabolism under situations associated to
      hyperleptinemia.

PMID- 20056821
TI  - Effects of bone morphogenetic protein (BMP) on adrenocorticotropin production by
      pituitary corticotrope cells: involvement of up-regulation of BMP receptor
      signaling by somatostatin analogs.
AB  - The mechanism by which somatostatin analogs suppress ACTH production by
      corticotropinomas has yet to be fully elucidated. We here studied the effects of
      somatostatin analogs on ACTH secretion using mouse corticotrope AtT20 cells
      focusing on the biological activity of bone morphogenetic proteins (BMPs). BMP
      ligands, receptors and Smads, and somatostatin receptors (SSTRs)-2, -3, and -5
      were expressed in AtT20 cells. BMP-2, -4, -6, and -7 decreased basal ACTH
      production with BMP-4 effects being the most prominent. BMP-4 also inhibited CRH
      induced ACTH production and proopiomelanocortin (POMC) transcription. However,
      the decrease in CRH-induced cAMP accumulation caused by BMP-4 was not sufficient
      to completely account for BMP-4 actions, indicating that ACTH suppression by BMPs
      was not directly linked to cAMP inhibition. CRH-activated ERK1/ERK2, p38-MAPK,
      stress-activated protein kinase/c-Jun NH(2)-terminal kinase, protein kinase C,
      and Akt pathways and CRH-induced ACTH synthesis was significantly decreased in
      the presence of U0126 or SB203580. Because BMPs attenuated CRH-induced ERK and
      p38 phosphorylation, it was suggested that BMP-4 suppresses ACTH production by
      inhibiting CRH-induced ERK and p38 phosphorylation. Somatostatin analogs
      octreotide and pasireotide (SOM230) significantly suppressed CRH-induced ACTH and
      cAMP production in AtT20 cells and reduced ERK and p38 phosphorylation. Notably,
      CRH-induced ACTH production was enhanced in the presence of noggin, a BMP-binding
      protein. The inhibitory effects of octreotide and SOM230 on CRH-induced ACTH
      production were also attenuated by noggin, implying that the endogenous BMP
      system plays a key role in inhibiting CRH-induced ACTH production by AtT20 cells.
      The findings that OCT and SOM230 up-regulated BMP-Smad1/Smad5/Smad8 signaling and
      ALK-3 and BMPRII and down-regulated inhibitory Smad6/7 establish that the
      activation of endogenous BMP system is functionally involved in the mechanism by
      which somatostatin analogs suppress CRH-induced ACTH production.

PMID- 20056822
TI  - Mice lacking hepatic lipase are lean and protected against diet-induced obesity
      and hepatic steatosis.
AB  - Hepatic lipase (HL)-mediated lipoprotein hydrolysis provides free fatty acids for
      energy, storage, and nutrient signaling and may play a role in energy
      homeostasis. Because HL-activity increases with increased visceral fat, we
      hypothesized that increased HL-activity favors weight gain and obesity and
      consequently, that HL deficiency would reduce body fat stores and protect against
      diet-induced obesity. To test this hypothesis, we compared wild-type mice (with
      endogenous HL) and mice genetically deficient in HL with respect to daily body
      weight and food intake, body composition, and adipocyte size on both chow and
      high-fat (HF) diets. Key determinants of energy expenditure, including rate of
      oxygen consumption, heat production, and locomotor activity, were measured by
      indirect calorimetry. HL-deficient mice exhibited reduced weight gain on both
      diets (by 32%, chow; by 50%, HF; both P < 0.0001, n = 6-7 per genotype), effects
      that were associated with reduced average daily food intake (by 22-30% on both
      diets, P < 0.0001) and a modest increase in the rate of oxygen consumption (by
      25%, P < 0.003) during the light cycle. Moreover, in mice fed the HF diet, HL
      deficiency reduced both body fat (by 30%, P < 0.0001) and adipocyte size (by 53%,
      P < 0.01) and fully prevented the development of hepatic steatosis. Also, HL
      deficiency reduced adipose tissue macrophage content, consistent with reduced
      inflammation and a lean phenotype. Our results demonstrate that in mice, HL
      deficiency protects against diet-induced obesity and its hepatic sequelae.
      Inhibition of HL-activity may therefore have value in the prevention and/or
      treatment of obesity.

PMID- 20056823
TI  - LEFTY, a member of the transforming growth factor-beta superfamily, inhibits
      uterine stromal cell differentiation: a novel autocrine role.
AB  - LEFTY is expressed in normal endometrium in cells that decidualize. To understand
      the importance of this expression, we have studied the effect of LEFTY on
      decidualization in vitro and in vivo. Exposure of human uterine fibroblast (HuF)
      cells to recombinant LEFTY blocked the induction of the decidual differentiation
      specific marker genes, IGFBP1 (IGF-binding protein 1) and PRL (prolactin) in
      response to medroxyprogesterone acetate, estradiol, and prostaglandin E2. The
      inhibitory effect was associated with decreased induction of the transcription
      factors ETS1 and FOXO1, both of which are essential for decidualization.
      Overexpression of LEFTY in decidualized HuF cells with an adenovirus that
      transduced LEFTY caused a marked decrease in IGFBP1 secretion, and withdrawal of
      medroxyprogesterone acetate from decidualized cells resulted in a decrease in
      IGFBP1 secretion and an increase in LEFTY expression. Moreover, overexpression of
      LEFTY in decidualized cells reprogrammed the cells to a less differentiated state
      and attenuated expression of decidual markers. Uterine decidualization was
      markedly attenuated and litter size was significantly reduced by retroviral
      transduction of LEFTY in the uterine horns of pregnant mice or by induction of
      LEFTY expression by doxycycline treatment in Tet-On conditional LEFTY transgenic
      pregnant mice. In addition, administration of the contraceptive agent
      drospirenone to ovariectomized mice induced a marked increase in LEFTY expression
      and inhibited decidualization. Taken together, these finding indicate that LEFTY
      acts as a molecular switch that modulates both the induction of decidual
      differentiation and the maintenance of a decidualized state. Because decidual
      cells express abundant amounts of LEFTY, the action of LEFTY on decidualization
      occurs by an autocrine mechanism.

PMID- 20056824
TI  - Doublesex- and Mab-3-related transcription factor-1 repression of aromatase
      transcription, a possible mechanism favoring the male pathway in tilapia.
AB  - Doublesex- and Mab-3-related transcription factor-1 (Dmrt1) is an important
      transcription factor implicated in early testicular differentiation in
      vertebrates, but its target genes are largely unknown. In the Nile tilapia,
      estrogen is the natural inducer of ovarian differentiation. Our recent studies
      have shown that Forkhead-l2 up-regulated transcription of the Cyp19a1a gene
      (aromatase) in the gonads in a female-specific manner. However, the upstream
      factor(s) down-regulating Cyp19a1a expression during testicular differentiation
      remains unclear. In the present study, we used in vitro (promoter analysis) and
      in vivo (transgenesis and in situ hybridization) approaches to examine whether
      Dmrt1 inhibits Cyp19a1a's transcriptional activity. The in vitro analysis using
      luciferase assays revealed that Dmrt1 repressed basal as well as Ad4BP/SF-1
      activated Cyp19a1a transcription in HEK 293 cells. Luciferase assays with various
      deletions of Dmrt1 also showed that the Doublesex and Mab-3 domain is essential
      for the repression. In vitro-translated Dmrt1 and the nuclear extract from
      tilapia testis could directly bind to the palindrome sequence ACATATGT in the
      Cyp19a1a promoter, as determined by EMSAs. Transgenic overexpression of Dmrt1 in
      XX fish resulted in decreased aromatase gene expression, reduced serum estradiol
      17beta levels, retardation of the ovarian cavity's development, varying degrees
      of follicular degeneration, and even a partial to complete sex reversal. Our
      results indicate that aromatase is one of the targets of Dmrt1. Dmrt1 suppresses
      the female pathway by repressing aromatase gene transcription and estrogen
      production in the gonads of tilapia and possibly other vertebrates.

PMID- 20056825
TI  - Precursor cells in mouse islets generate new beta-cells in vivo during aging and
      after islet injury.
AB  - Whereas it is believed that the pancreatic duct contains endocrine precursors,
      the presence of insulin progenitor cells residing in islets remain controversial.
      We tested whether pancreatic islets of adult mice contain precursor beta-cells
      that initiate insulin synthesis during aging and after islet injury. We used
      bigenic mice in which the activation of an inducible form of Cre recombinase by a
      one-time pulse of tamoxifen results in the permanent expression of a floxed human
      placental alkaline phosphatase (PLAP) gene in 30% of pancreatic beta-cells. If
      islets contain PLAP(-) precursor cells that differentiate into beta-cells (PLAP(
      )IN(+)), a decrease in the percentage of PLAP(+)IN(+) cells per total number of
      IN(+) cells would occur. Conversely, if islets contain PLAP(+)IN(-) precursors
      that initiate synthesis of insulin, the percentage of PLAP(+)IN(+) cells would
      increase. Confocal microscope analysis revealed that the percentage of
      PLAP(+)IN(+) cells in islets increased from 30 to 45% at 6 months and to 60% at
      12 months. The augmentation in the level of PLAP in islets with time was
      confirmed by real-time PCR. Our studies also demonstrate that the percentage of
      PLAP(+)IN(+) cells in islets increased after islet injury and identified putative
      precursors in islets. We postulate that PLAP(+)IN(-) precursors differentiate
      into insulin-positive cells that participate in a slow renewal of the beta-cell
      mass during aging and replenish beta-cells eliminated by injury.

PMID- 20056826
TI  - Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm
      production via a reversible hormone-regulated mechanism.
AB  - Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high
      affinity to the androgen receptor (AR) and blocks the action of gonadal hormones
      on male reproductive organs. An alternative mechanism of action of Vinclozolin
      involves transgenerational effects on the male reproductive tract. We previously
      reported in utero Vinclozolin exposure-induced prostatitis (prostate
      inflammation) in postpubertal rats concurrent with down-regulation of AR and
      increased nuclear factor-kappaB activation. We postulated the male reproductive
      abnormalities induced by in utero Vinclozolin exposure could be reversed by
      testosterone supplementation, in contrast to the permanent modifications
      involving DNA methyltransferases (Dnmts) described by others. To test this
      hypothesis, we administered high-dose testosterone at puberty to Vinclozolin
      treated rats and determined the effect on anogenital distance (AGD); testicular
      germ cell apoptosis, concentration of elongated spermatids, and the onset of
      prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression.
      Consistent with previous reports, in utero exposure to Vinclozolin significantly
      reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated
      spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed
      males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized
      AGD, reduced germ cell apoptosis, and restored elongated spermatid number.
      Testosterone restored AR and nuclear factor-kappaB expression in the prostate and
      abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident
      with in utero Vinclozolin exposure and was not normalized after testosterone
      treatment. These data demonstrate in utero Vinclozolin-induced male reproductive
      tract abnormalities are AR mediated and reversible and involve a mechanism
      independent of Dnmt expression.

PMID- 20056827
TI  - Thyroid hormone regulation of gene expression in the developing rat fetal
      cerebral cortex: prominent role of the Ca2+/calmodulin-dependent protein kinase
      IV pathway.
AB  - Thyroid hormones influence brain development through regulation of gene
      expression mediated by nuclear receptors. Nuclear receptor concentration
      increases rapidly in the human fetus during the second trimester, a period of
      high sensitivity of the brain to thyroid hormones. In the rat, the equivalent
      period is the last quarter of pregnancy. However, little is known about thyroid
      hormone action in the fetal brain, and in rodents, most thyroid hormone-regulated
      genes have been identified during the postnatal period. To identify potential
      targets of thyroid hormone in the fetal brain, we induced maternal and fetal
      hypothyroidism by maternal thyroidectomy followed by antithyroid drug (2-mercapto
      1-methylimidazole) treatment. Microarray analysis identified differentially
      expressed genes in the cerebral cortex of hypothyroid fetuses on d 21 after
      conception. Gene function analysis revealed genes involved in the biogenesis of
      the cytoskeleton, neuronal migration and growth, and branching of neurites.
      Twenty percent of the differentially expressed genes were related to each other
      centered on the Ca(2+) and calmodulin-activated kinase (Camk4) pathway. Camk4 was
      regulated directly by T(3) in primary cultured neurons from fetal cortex, and the
      Camk4 protein was also induced by thyroid hormone. No differentially expressed
      genes were recovered when euthyroid fetuses from hypothyroid mothers were
      compared with fetuses from normal mothers. Although the results do not rule out a
      specific contribution from the mother, especially at earlier stages of pregnancy,
      they indicate that the main regulators of thyroid hormone-dependent, fetal brain
      gene expression near term are the fetal thyroid hormones.

PMID- 20056828
TI  - An increase in the circulating concentration of monocyte chemoattractant protein
      1 elicits systemic insulin resistance irrespective of adipose tissue inflammation
      in mice.
AB  - Chronic inflammation in adipose tissue is thought to be important for the
      development of insulin resistance in obesity. Furthermore, the level of monocyte
      chemoattractant protein-1 (MCP-1) is increased not only in adipose tissue but
      also in the circulation in association with obesity. However, it has remained
      unclear to what extent the increased circulating level of MCP-1 contributes to
      insulin resistance. We have now examined the relevance of circulating MCP-1 to
      the development of insulin resistance in mice. The plasma concentration of MCP-1
      was increased chronically or acutely in mice to the level observed in obese
      animals by chronic subcutaneous infusion of recombinant MCP-1 with an osmotic
      pump or by acute intravenous infusion of MCP-1 with an infusion pump,
      respectively. Whole-body metabolic parameters as well as inflammatory changes in
      adipose tissue were examined. A chronic increase in the circulating level of MCP
      1 induced insulin resistance, macrophage infiltration into adipose tissue, and an
      increase in hepatic triacylglycerol content. An acute increase in the circulating
      MCP-1 concentration also induced insulin resistance but not macrophage
      infiltration into adipose tissue. In addition, inhibition of signaling by MCP-1
      and its receptor CCR2 by administration of a novel CCR2 antagonist ameliorated
      insulin resistance in mice fed a high-fat diet without affecting macrophage
      infiltration into adipose tissue. These data indicate that an increase in the
      concentration of MCP-1 in the circulation is sufficient to induce systemic
      insulin resistance irrespective of adipose tissue inflammation.

PMID- 20056829
TI  - Growth hormone secretagogues reduce transient outward K+ current via
      phospholipase C/protein kinase C signaling pathway in rat ventricular myocytes.
AB  - Endogenous ghrelin and its synthetic counterpart hexarelin are peptide GH
      secretagogues (GHS) that exert a positive ionotropic effect in the cardiovascular
      system. The mechanism by which GHS modulate cardiac electrophysiology properties
      to alter myocyte contraction is poorly understood. In the present study, we
      examined whether GHS regulates the transient outward potassium current (I(to)) as
      well as the putative intracellular signaling cascade responsible for such
      regulation. GHS and experimental agents were applied locally onto freshly
      isolated adult Sprague-Dawley rat ventricular myocytes and action potential
      morphology and I(to) was recorded using nystatin-perforated whole-cell patch
      clamp recording technique. Under current clamp, ghrelin and hexarelin (10 nm)
      significantly prolonged action potential duration. Under voltage clamp, hexarelin
      and ghrelin inhibited I(to) in a concentration-dependent manner. This inhibition
      was abolished in the presence of the GHS receptor (GHS-R) antagonist [D-Lys(3)]GH
      releasing peptide-6 (10 microm) and GHS-R1a-specific antagonist BIM28163 (1
      microm). GHS-induced I(to) inhibition was totally reversed by the phospholipase C
      inhibitor U73122 (5 microm) and protein kinase C inhibitors GO6983 (1 microm) and
      calphostin C (0.1 microm) but not by the cAMP antagonist Rp-cAMP (100 microm) or
      the PKA inhibitor H89 (1 microm). We conclude that hexarelin and ghrelin activate
      phospholipase C and protein kinase C signaling cascade through the stimulation of
      the GHS-R, resulting in a decrease in the I(to) current and subsequent
      prolongation of action potential duration.

PMID- 20056830
TI  - Effects of estradiol on cerebrospinal fluid levels of agouti-related protein in
      ovariectomized rhesus monkeys.
AB  - Hypothalamic proopiomelanocortin (POMC)-derived MSH peptides and the melanocortin
      receptor antagonist, agouti-related protein (AgRP), interact to regulate energy
      balance. Both POMC and AgRP neurons express estrogen receptors, but little is
      known about estrogen regulation of the melanocortin system in the primate. We
      have therefore examined the effects of physiological doses of estradiol (E2) on
      POMC and AgRP in lumbar cerebrospinal fluid (CSF) of ovariectomized monkeys. POMC
      prohormone was measured by ELISA. AgRP was measured by RIA (sensitive for the
      more biologically active C-terminal AgRP(83-132) but also detects full-length
      AgRP) and by ELISA (measures primarily full length AgRP). In the first
      experiment, 14 animals were studied before and after 3 wk of E2. CSF POMC did not
      change, but AgRP(RIA) decreased from 7.9 +/- 1.2 to 4.7 +/- 1.2 fmol/ml after E2
      (P = 0.03) and the POMC/AgRP(RIA) ratio increased from 4.2 +/- 0.89 to 6.8 +/-
      1.04 (P = 0.04). AgRP(ELISA) did not change, but the ratio of AgRP(RIA) compared
      with AgRP(ELISA) was reduced after E2 (P = 0.02). In the second experiment, 11
      animals were studied after 6 wk of E2, and similar changes were noted. The degree
      of AgRP(RIA) suppression with E2 was inversely related to body mass index (r =
      0.569; P = 0.03). These results show for the first time that E2 suppresses AgRP(C
      terminal) in CSF, increases the POMC to AgRP ratio, and may decrease AgRP
      processing, thus leading to increased melanocortin signaling. Furthermore,
      obesity was associated with resistance to the suppressive effects of E2 on AgRP,
      analogous to what is seen with obesity and leptin resistance.

PMID- 20056831
TI  - Kit ligand and the somatostatin receptor antagonist, BIM-23627, stimulate in
      vitro resting follicle growth in the neonatal mouse ovary.
AB  - In the mammalian ovary, kit ligand (KL), coded by a cAMP-stimulatable gene, is a
      protein that promotes initiation of follicle growth. The neuropeptide
      somatostatin (SST) is a small peptide that inhibits cAMP generation in many cell
      types. Consequently, SST receptor agonists might alter KL production and
      subsequent follicle growth. The present study was undertaken to look for the
      existence of a functional SST system in the mouse ovary, to test the effects of
      the SST receptor 2 (SSTR-2) antagonist BIM-23627 on in vitro folliculogenesis,
      and to compare them with those of KL, which was demonstrated to stimulate
      follicle growth in the neonatal rat ovary. Pairs of ovaries from 5-d-old mice
      were incubated in vitro during 15 d in the presence of either KL or BIM-23627.
      For every mouse, one ovary was cultured in culture medium (control), and the
      other ovary was cultured in the presence of either KL or BIM-23627. After 5, 10,
      and 15 d culture, the ovaries were histologically assessed for the content of
      primordial, primary, and secondary follicles. The SSTR-2 and -5, but not SST,
      were identified at the transcriptional and translational (mainly in granulosa
      cells) levels. Both KL and BIM-23627 triggered a reduction of the percentages of
      primordial follicles and an increase of the percentages of primary and secondary
      follicles when compared with control ovaries from the same animal. In conclusion,
      extraovarian SST, acting through its receptors 2 and 5 present on granulosa
      cells, may be involved in mouse folliculogenesis by reducing recruitment of
      resting follicles.

PMID- 20056832
TI  - Acute insulin signaling in pancreatic beta-cells is mediated by multiple Raf-1
      dependent pathways.
AB  - Insulin enhances the proliferation and survival of pancreatic beta-cells, but its
      mechanisms remain unclear. We hypothesized that Raf-1, a kinase upstream of both
      ERK and Bad, might be a critical target of insulin in beta-cells. To test this
      hypothesis, we treated human and mouse islets as well as MIN6 beta-cells with
      multiple insulin concentrations and examined putative downstream targets using
      immunoblotting, immunoprecipitation, quantitative fluorescent imaging, and cell
      death assays. Low doses of insulin rapidly activated Raf-1 by dephosphorylating
      serine 259 and phosphorylating serine 338 in human islets, mouse islets, and MIN6
      cells. The phosphorylation of ERK by insulin was eliminated by exposure to a Raf
      inhibitor (GW5074) or transfection with a dominant-negative Raf-1 mutant. Insulin
      also enhanced the interaction between mitochondrial Raf-1 and Bcl-2 agonist of
      cell death (Bad), promoting Bad inactivation via its phosphorylation on serine
      112. Insulin-stimulated ERK phosphorylation was abrogated by calcium chelation,
      calcineurin and calmodulin-dependent protein kinase II inhibitors, and Ned-19, a
      nicotinic acid adenine dinucleotide phosphate receptor (NAADPR) antagonist.
      Blocking Raf-1 and Ca(2+) signaling resulted in nonadditive beta-cell death.
      Autocrine insulin signaling partly accounted for the effects of glucose on ERK
      phosphorylation. Our results demonstrate that Raf-1 is a critical target of
      insulin in primary beta-cells. Activation of Raf-1 leads to both an ERK-dependent
      pathway that involves nicotinic acid adenine dinucleotide phosphate-sensitive
      Ca(2+) stores and Ca(2+)-dependent phosphorylation events, and an ERK-independent
      pathway that involves Bad inactivation at the mitochondria. Together our findings
      identify a novel insulin signaling pathway in beta-cells and shed light on
      insulin's antiapoptotic and mitogenic mechanisms.

PMID- 20056833
TI  - 17beta-estradiol accelerates tumor onset and decreases survival in a transgenic
      mouse model of ovarian cancer.
AB  - Epithelial ovarian cancer is thought to be derived from the ovarian surface
      epithelium (OSE) but often goes undetected in the early stages, and as a result,
      the factors that contribute to its initiation and progression remain poorly
      understood. Epidemiological studies have suggested that the female steroid
      hormones are involved in ovarian carcinogenesis and that women who use hormone
      replacement therapy are at increased risk of developing the disease. A novel
      transgenic mouse model of ovarian cancer (tgCAG-LS-TAg) was developed to examine
      the role of the female reproductive steroid hormones [17beta-estradiol (E(2)) and
      progesterone (P(4))] on the initiation, progression, and pathology of ovarian
      cancer. The mouse model uses the Cre-LoxP system to induce expression of the
      simian virus 40 large and small T antigens (SV40 TAg). After targeted induction
      of the oncogene in the OSE, mice develop poorly differentiated ovarian tumors,
      tumor dissemination to tissues within the abdominal cavity, and a subset develops
      hemorrhagic ascites. Treatment with P(4) had no impact on the disease, but E(2)
      altered the pathophysiology, resulting in an earlier onset of tumors, decreased
      overall survival time, and a distinctive papillary histology. Normal ovaries
      collected from mice treated with E(2), but lacking expression of SV40 TAg,
      displayed an increase in the areas of columnar and hyperplastic OSE cells
      compared to placebo-treated controls. A better understanding of the mechanisms by
      which E(2) alters the morphology of normal OSE cells and reduces survival in this
      mouse model may translate into improved prevention and treatment options for
      women using hormone replacement therapy.

PMID- 20056834
TI  - Inhibition of glycogen synthase kinase 3beta (GSK3beta) decreases inflammatory
      responses in brain endothelial cells.
AB  - Immune mediators and leukocyte engagement of brain microvascular endothelial
      cells (BMVECs) contribute to blood-brain barrier impairment during
      neuroinflammation. Glycogen synthase kinase 3beta (GSK3beta) was recently
      identified as a potent regulator of immune responses in in vitro systems and
      animal models. However, the role of GSK3beta in regulation of immune endothelial
      functions remains undetermined. Here we evaluated the effect of GSK3beta
      inhibition on the regulation of inflammatory responses in BMVECs. A focused PCR
      gene array of 84 genes was performed to identify the cytokine and chemokine gene
      expression profile in tumor necrosis factor (TNF) alpha-stimulated BMVECs after
      GSK3beta inactivation by specific inhibitors. Fifteen of 39 genes induced by
      TNFalpha stimulation were down-regulated after GSK3beta inhibition. Genes known
      to contribute to neuroinflammation that were most negatively affected by GSK3beta
      inactivation included IP-10/CXCL10, MCP-1/CCL2, IL-8/CXCL8, RANTES/CCL5, and
      Groalpha/CXCL1. GSK3beta suppression resulted in diminished secretion of these
      proinflammatory mediators by inflamed BMVECs detected by ELISA. GSK3beta
      inhibition in BMVECs reduced adhesion molecule expression as well as monocyte
      adhesion to and migration across cytokine stimulated BMVEC monolayers.
      Interactions of monocytes with TNFalpha-activated BMVECs led to barrier
      disruption, and GSK3beta suppression in the endothelium restored barrier
      integrity. GSK3beta inhibition in vivo substantially decreased leukocyte adhesion
      to brain endothelium under inflammatory conditions. In summary, inhibition of
      GSK3beta emerges as an important target for stabilization of the blood-brain
      barrier in neuroinflammation.

PMID- 20056835
TI  - Pulmonary infection with an interferon-gamma-producing Cryptococcus neoformans
      strain results in classical macrophage activation and protection.
AB  - Alternative macrophage activation is associated with exacerbated disease in
      murine models of pulmonary cryptococcosis. The present study evaluated the
      efficacy of interferon-gamma transgene expression by Cryptococcus neoformans
      strain H99gamma in abrogating alternative macrophage activation in infected mice.
      Macrophage recruitment into the lungs of mice after infection with C. neoformans
      strain H99gamma was comparable with that observed in mice challenged with wild
      type C. neoformans. However, pulmonary infection in mice with C. neoformans
      strain H99gamma was associated with reduced pulmonary fungal burden, increased
      pulmonary Th1-type and interleukin-17 cytokine production, and classical
      macrophage activation as evidenced by increased inducible nitric oxide synthase
      expression, histological evidence of enhanced macrophage fungicidal activity, and
      resolution of inflammation. In contrast, progressive pulmonary infection,
      enhanced Th2-type cytokine production, and the induction of alternatively
      activated macrophages expressing arginase-1, found in inflammatory zone 1, Ym1,
      and macrophage mannose receptor were observed in the lungs of mice infected with
      wild-type C. neoformans. These alternatively activated macrophages were also
      shown to harbor highly encapsulated, replicating cryptococci. Our results
      demonstrate that pulmonary infection with C. neoformans strain H99gamma results
      in the induction of classically activated macrophages and promotes fungal
      clearance. These studies indicate that phenotype, as opposed to quantity, of
      infiltrating macrophages correlates with protection against pulmonary C.
      neoformans infection.

PMID- 20056836
TI  - Tissue deposits of IgA-binding streptococcal M proteins in IgA nephropathy and
      Henoch-Schonlein purpura.
AB  - IgA nephropathy (IgAN) and Henoch-Schonlein purpura (HSP) are diseases
      characterized by IgA deposits in the kidney and/or skin. Both may arise after
      upper respiratory tract infections, but the pathogenic mechanisms governing these
      diseases remain unclear. Patients with IgAN (n = 16) and HSP (n = 17) were
      included in this study aimed at examining whether IgA-binding M proteins of group
      A streptococci could be involved. As M proteins vary in sequence, the study
      focused on the IgA-binding-region (IgA-BR) of three different M proteins: M4,
      M22, and M60. Renal tissue from IgAN and HSP patients and skin from HSP patients
      were examined for deposits of streptococcal IgA-BR by immunohistochemistry and
      electron microscopy using specific antibodies, and a skin sample from a HSP
      patient was examined by mass spectrometry. IgA-BR deposits were detected in 10/16
      IgAN kidneys and 7/13 HSP kidneys. Electron microscopy demonstrated deposits of
      IgA-BRs in the mesangial matrix and glomerular basement membrane, which
      colocalized with IgA. Skin samples exhibited IgA-BR deposits in 4/5 biopsies, a
      result confirmed by mass spectrometry in one patient. IgA-BR deposits were not
      detected in normal kidney and skin samples. Taken together, these results
      demonstrate IgA-BR from streptococcal M proteins in patient tissues. IgA-BR,
      would on gaining access to the circulation, encounter circulatory IgA and form a
      complex with IgA-Fc that could deposit in tissues and contribute to the
      pathogenesis of IgAN and HSP.

PMID- 20056837
TI  - Platelet, not endothelial, P-selectin expression contributes to generation of
      immunity in cutaneous contact hypersensitivity.
AB  - Leukocyte extravasation is a prerequisite for host defense and autoimmunity
      alike. Detailed understanding of the tightly controlled and overlapping sequences
      of leukocyte extravasation might aid development of novel therapeutic strategies.
      Leukocyte extravasation is initiated by interaction of selectins with appropriate
      carbohydrate ligands. Lack of P-selectin expression leads to decreased contact
      hypersensitivity responses. Yet, it remains unclear if this is due to inhibition
      of leukocyte extravasation to the skin or due to interference with initial immune
      activation in lymph nodes. In line with previous data, we here report a decreased
      contact hypersensitivity response, induced by 2,4,-dinitrofluorobenzene (DNFB),
      in P-selectin-deficient mice. Eliciting an immune reaction towards DNFB in wild
      type mice, followed by adoptive transfer to P-selectin-deficient mice, had no
      impact on inflammatory response in recipients. This was significantly reduced in
      wild-type recipient mice adoptively transferred with DNFB immunity generated in P
      selectin-deficient mice. To investigate if platelet or endothelial P-selectin was
      involved, mice solely lacking platelet P-selectin expression generated by bone
      marrow transplantation were used. Adoptive transfer of immunity from wild-type
      mice reconstituted with P-selectin-deficient bone marrow led to a decrease of
      inflammatory response. Comparing this decrease to the one observed using P
      selectin-deficient mice, no differences were observed. Our observations indicate
      that platelet, not endothelial, P-selectin contributes to generation of immunity
      in DNFB-induced contact hypersensitivity.

PMID- 20056838
TI  - Involvement of CYR61 and CTGF in the fascin-mediated proliferation and
      invasiveness of esophageal squamous cell carcinomas cells.
AB  - Fascin is overexpressed in esophageal squamous cell [corrected] carcinoma (ESCC)
      and involved in the proliferation and invasiveness of ESCC cells. In this study,
      we retrospectively examined the expression of fascin in ESCC samples by
      immunohistochemistry and revealed that overexpression of fascin was related to
      poor patient survival. RNAi-mediated knockdown of fascin in ESCC cells
      significantly inhibited cell proliferation and invasiveness, whereas forced
      expression of fascin in immortalized esophageal epithelial cells accelerated cell
      proliferation and invasiveness. To explore the underlying mechanism, cDNA
      microarray was performed to identify the differential gene expression profiles
      between a fascin-depleted cell line by RNAi and the corresponding control ESCC
      cells. Results showed that 296 genes were differentially expressed on fascin
      depletion. In this study, we focused on two down-regulated genes: CYR61 and CTGF.
      We found that restored expression of either CYR61 or CTGF led to a recovery of
      the suppression of cellular proliferation and invasiveness induced by down
      regulation of fascin expression; the protein level of CYR61 and CTGF were up
      regulated in ESCCs and their expression pattern correlated with fascin
      overexpression. Finally, analysis of signal transduction revealed that fascin
      affected the expressions of CYR61 and CTGF through transforming growth factor
      (TGF)-beta pathway. Taken together, we propose that fascin regulates the
      proliferation and invasiveness of ESCC cells by modulating the expression of CTGF
      and CYR61 via TGF-beta pathway.

PMID- 20056839
TI  - Weaving hypothesis of cardiomyocyte sarcomeres: discovery of periodic broadening
      and narrowing of intercalated disk during volume-load change.
AB  - To investigate how cardiomyocytes change their length, echocardiographic and
      morphological studies were performed on rabbit hearts that were subjected to
      volume overload, overload removal, and repeated cycles of overload and overload
      removal. These conditions were created by arterio-venous fistula between the
      carotid artery and jugular vein, closure of the fistula, and cycles of repeatedly
      forming and closing fistula, respectively. After overload, hearts dilated and
      myocytes elongated. Intercalated disks repeatedly broadened and narrowed with a 2
      day cycle, which continued for 8 weeks in many animals. The cycle consisted of
      shifts between five modes characterized by two interdigitation elongation-and
      shortenings as follows: (I) flat with short ( approximately 1/4 to approximately
      1/3 sarcomere long) interdigitations; (II) flat with long (one sarcomere long)
      interdigitations; (III) grooved with short interdigitations; (IV) grooved with
      long interdigitations; (V) flat with short interdigitations intermingled by
      sporadic long interdigitations; and return to (I). After overload removal, hearts
      contracted and myocytes shortened with similar 2-day broadening and narrowing
      cycle of intercalated disks, in which the five modes were reversed. Repeated
      overload and overload removal resulted in the repetition of myocyte elongation
      and shortening. We hypothesize that a single elongation-and-shortening event
      creates or disposes one sarcomere layer, and the two consecutive elongation-and
      shortenings occur complementarily to each other so that the disks return to their
      original state after each cycle. Our hypothesis predicts that intercalated disks
      weave and unravel one sarcomere per myocyte per day.

PMID- 20056840
TI  - Preventive effect of Notch signaling inhibition by a gamma-secretase inhibitor on
      peritoneal dialysis fluid-induced peritoneal fibrosis in rats.
AB  - Peritoneal fibrosis, a major complication of peritoneal dialysis, limits the
      effectiveness of peritoneal dialysis as a treatment of end-stage renal disease.
      Preventing this complication by identifying targets for therapy has recently
      received much attention. In the present study, we showed that Notch signaling was
      highly activated in rats in peritoneal dialysis fluid-induced fibrotic
      peritoneum, as indicated by increased expression of Jagged-1, Notch-1, and HES-1.
      Blocking Notch signaling activation by intraperitoneal injection of a gamma
      secretase inhibitor, DAPT, significantly attenuated peritoneal fibrosis as
      indicated by the decreased expression of alpha-smooth muscle actin, collagen I,
      and vascular endothelial growth factor as well as increased expression of E
      cadherin. Moreover, compared with control rats, DAPT-treated rats had a thinner
      peritoneum with less extracellular matrix accumulation, a lower mass transfer of
      glucose, and a higher ultrafiltration rate. In addition, transforming growth
      factor (TGF)-beta1 induced Notch signaling activation in primary rat peritoneal
      mesothelial cells. DAPT blocked this TGF-beta1-induced Notch signaling activation
      and therefore significantly inhibited TGF-beta1-induced expression of alpha
      smooth muscle actin, collagen I, and vascular endothelial growth factor. Thus, a
      gamma-secretase inhibitor that interferes with Notch signaling prevents
      biochemical, histological, and functional consequences of peritoneal fibrosis
      through inhibiting epithelial to mesenchymal transition of rat peritoneal
      mesothelial cells. These results support the use of gamma-secretase inhibitors as
      a novel therapeutic approach for peritoneal fibrosis.

PMID- 20056842
TI  - Kallikrein-related peptidase 4: a new activator of the aberrantly expressed
      protease-activated receptor 1 in colon cancer cells.
AB  - Certain serine proteases are considered to be signaling molecules that act
      through protease-activated receptors (PARs). Our recent studies have implicated
      PAR1 and PAR4 (thrombin receptors) and PAR2 (trypsin receptor) in human colon
      cancer growth. Here we analyzed the expression of KLK4, a member of the
      kallikrein-related peptidase (KLK) family of serine proteases and explored
      whether this member can activate PAR1 and PAR2 in human colon cancer cells.
      Immunohistochemistry showed KLK4 expression in human colon adenocarcinomas and
      its absence in normal epithelia. KLK4 (1 micromol/L) initiated loss of PAR1 and
      PAR2 from the HT29 cell surface as well as increased intracellular calcium
      transients in HT29 cells. This KLK4-induced Ca2+ flux was abrogated after an
      initial challenge of the cells with TRAP (SFLLR-NH2; 100 micromol/L), which is
      known to desensitize PAR1 and PAR2. Interestingly, PAR1 blocking antibody, which
      inhibits cleavage and activation by thrombin, dramatically reduced KLK4-induced
      Ca2+ influx, but blocking cleavage of PAR2 failed to attenuate the KLK4-induced
      Ca2+ flux. Consistently, desensitization with AP1 (TFFLR-NH2), targeting PAR1,
      attenuated most of the Ca2+ flux induced by KLK4. KLK4 also induced a rapid and
      significant ERK1/2 phosphorylation in HT29 cells. Our results demonstrate, for
      the first time, that KLK4 is aberrantly expressed in colon cancer and capable of
      inducing PAR1 signaling in cancer cells. These data suggest that KLK4 signaling
      via PAR1 may represent a novel pathway in colon tumorigenesis.

PMID- 20056841
TI  - Secreted frizzled-related protein 4: an angiogenesis inhibitor.
AB  - Wnt signaling is involved in developmental processes, cell proliferation, and
      cell migration. Secreted frizzled-related protein 4 (sFRP4) has been demonstrated
      to be a Wnt antagonist; however, its effects on endothelial cell migration and
      angiogenesis have not yet been reported. Using various in vitro assays, we show
      that sFRP4 inhibits endothelial cell migration and the development of sprouts and
      pseudopodia as well as disrupts the stability of endothelial rings in addition to
      inhibiting proliferation. sFRP4 interfered with endothelial cell functions by
      antagonizing the canonical Wnt/beta-catenin signaling pathway and the Wnt/planar
      cell polarity pathway. Furthermore, sFRP4 blocked the effect of vascular
      endothelial growth factor on endothelial cells. sFRP4 also selectively induced
      apoptotic events in endothelial cells by increasing cellular levels of reactive
      oxygen species. In vivo assays demonstrated a reduction in vascularity after
      sFRP4 treatment. Most importantly, sFRP4 restricted tumor growth in mice by
      interfering with endothelial cell function. The data demonstrate sFRP4 to be a
      potent angiogenesis inhibitor that warrants further investigation as a
      therapeutic agent in the control of angiogenesis-associated pathology.

PMID- 20056843
TI  - Origins of vascular disease: is fat where it's at?

PMID- 20056844
TI  - Point: Pulmonary edema does occur in human athletes performing heavy sea-level
      exercise.

PMID- 20056845
TI  - The effect of oxygen on dynamic cerebral autoregulation: critical role of
      hypocapnia.
AB  - Hypoxia is known to impair cerebral autoregulation (CA). Previous studies
      indicate that CA is profoundly affected by cerebrovascular tone, which is largely
      determined by the partial pressure of arterial O(2) and CO(2). However, hypoxic
      induced hyperventilation via respiratory chemoreflex activation causes
      hypocapnia, which may influence CA independent of partial pressure of arterial
      O(2). To identify the effect of O(2) on dynamic cerebral blood flow regulation,
      we examined the influence of normoxia, isocapnia hyperoxia, hypoxia, and hypoxia
      with consequent hypocapnia on dynamic CA. We measured heart rate, blood pressure,
      ventilatory parameters, and middle cerebral artery blood velocity (transcranial
      Doppler). Dynamic CA was assessed (n = 9) during each of four randomly assigned
      respiratory interventions: 1) normoxia (21% O(2)); 2) isocapnic hyperoxia (40%
      O(2)); 3) isocapnic hypoxia (14% O(2)); and 4) hypocapnic hypoxia (14% O(2)).
      During each condition, the rate of cerebral regulation (RoR), an established
      index of dynamic CA, was estimated during bilateral thigh cuff-induced transient
      hypotension. The RoR was unaltered during isocapnic hyperoxia. Isocapnic hypoxia
      attenuated the RoR (0.202 +/- 0.003/s; 27%; P = 0.043), indicating impairment in
      dynamic CA. In contrast, hypocapnic hypoxia increased RoR (0.444 +/- 0.069/s)
      from normoxia (0.311 +/- 0.054/s; +55%; P = 0.041). These findings indicated that
      hypoxia disrupts dynamic CA, but hypocapnia augments the dynamic CA response.
      Because hypocapnia is a consequence of hypoxic-induced chemoreflex activation, it
      may provide a teleological means to effectively maintain dynamic CA in the face
      of prevailing arterial hypoxemia.

PMID- 20056846
TI  - Role of sympathetic responses on the hemodynamic consequences of rapid changes in
      posture in humans.
AB  - Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded
      by exposure to hypogravity (fractional, 0, or negative G(z)). For example, there
      is an exaggerated fall in eye-level arterial pressure (ELAP) early on during
      +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by 
      G(z) stress (head-down tilt; HDT), termed the "push-pull effect." The aim of the
      present study was to test the hypothesis that sympathetic responses contribute to
      the push-pull effect. Young, healthy subjects (n = 7 males and 3 females) were
      subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30
      degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four
      bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced
      design, and 1 min was allowed for recovery between tilts. This protocol was
      repeated during clonidine administration (2.5 microg/kg bolus over 30 min and
      then continuously at 0.36 microg x kg(-1) x h(-1)). Clonidine blunted the
      vasomotor responses to tilting, and this led to exaggerated changes in arterial
      pressure. Clonidine exerted little specific influence on the push-pull effect.
      Thus sympathetic responses appear neither to contribute to, nor protect against,
      the push-pull effect for the rate and duration of tilting imposed in the present
      study.

PMID- 20056848
TI  - Time course and mechanisms of adaptations in cardiorespiratory fitness with
      endurance training in older and young men.
AB  - The time-course and mechanisms of adaptation of cardiorespiratory fitness were
      examined in 8 older (O) (68 +/- 7 yr old) and 8 young (Y) (23 +/- 5 yr old) men
      pretraining and at 3, 6, 9, and 12 wk of training. Training was performed on a
      cycle ergometer three times per week for 45 min at approximately 70% of maximal
      oxygen uptake (Vo(2 max)). Vo(2 max) increased within 3 wk with further increases
      observed posttraining in both O (+31%) and Y (+18%), (P < 0.05). Maximal cardiac
      output (Q(max), open-circuit acetylene) and stroke volume were higher in O and Y
      after 3 wk with further increases after 9 wk of training (P < 0.05). Maximal
      arterial-venous oxygen difference (a-vO(2 diff)) was higher at weeks 3 and 6 and
      posttraining compared with pretraining in O and Y (P < 0.05). In O, approximately
      69% of the increase in Vo(2 max) from pre- to posttraining was explained by an
      increased Q(max) with the remaining approximately 31% explained by a widened a
      vO(2 diff). This proportion of Q and a-vO(2 diff) contributions to the increase
      in Vo(2 max) was consistent throughout testing in O. In Y, 56% of the pre- to
      posttraining increase in Vo(2 max) was attributed to a greater Q(max) and 44% to
      a widened a-vO(2 diff). Early adaptations (first 3 wk) mainly relied on a widened
      maximal a-vO(2 diff) (approximately 66%) whereas further increases in Vo(2 max)
      were exclusively explained by a greater Q(max). In conclusion, with short-term
      training O and Y significantly increased their Vo(2 max); however, the proportion
      of Vo(2 max) increase explained by Q(max) and maximal a-vO(2 diff) throughout
      training showed a different pattern by age group.

PMID- 20056847
TI  - Retrograde arterial leg blood flow during tilt-back from a head-up posture:
      importance of capacitive flows when arterial pressure changes.
AB  - The windkessel function of the arterial system converts the intermittent action
      of the heart into more continuous microcirculatory blood flow during diastole via
      the return of elastic energy stored in the walls of the arteries during systole.
      Might the same phenomenon occur regionally within the arterial system during
      tilting owing to regional differences in local arterial pressure imposed by
      gravity? We sought to test the hypothesis that during tilt-back from a head-up
      posture, the return of stored elastic energy in leg arteries would work to slow,
      or perhaps transiently reverse, the flow of blood in the femoral artery. Femoral
      artery blood flow and arterial pressure were recorded during tilt back from a 30
      degrees head-up posture to supine (approximately 0.5 G) in young, healthy
      subjects (n = 7 males and 3 females) before and during clonidine infusion. During
      control (no drug) conditions femoral artery blood flow ceased for an entire heart
      beat during tilt-back. During clonidine infusion femoral artery blood flow
      reversed for at least one entire heart beat during tilt-back, i.e., blood flow in
      the retrograde direction in the femoral artery from the leg into the abdomen.
      Thus substantial capacitive effects of tilting on leg blood flow occur in humans
      during mild changes in posture.

PMID- 20056850
TI  - Effect of airway opening on production of exhaled particles.
AB  - The technique of sampling exhaled air is attractive because it is noninvasive and
      so allows repeated sampling with ease and no risk for the patient. Knowledge of
      the biomarkers' origin is important to correctly understand and interpret the
      data. Endogenous particles, formed in the airways, are exhaled and reflect
      chemical composition of the respiratory tract lining fluid. However, the
      formation mechanisms and formation sites of these particles are unknown. We
      hypothesize that airway opening following airway closure causes production of
      airborne particles that are exhaled. The objective of this study was to examine
      production of exhaled particles following varying degrees of airway closure. Ten
      healthy volunteers performed three different breathing maneuvers in which the
      initial lung volume preceding an inspiration to total lung capacity was varied
      between functional residual capacity (FRC) and residual volume (RV). Exhaled
      particle number concentrations in the size interval 0.30-2.0 microm were
      recorded. Number concentrations of exhaled particles showed a 2- to 18-fold
      increase after exhalations to RV compared with exhalations where no airway
      closure was shown [8,500 (810-28,000) vs. 1,300 (330-13,000) particles/expired
      liter, P = 0.012]. The difference was most noticeable for the smaller size range
      of particles (<1 microm). There were significant correlations between particle
      concentrations for the different maneuvers. Our results show that airway
      reopening following airway closure is an important mechanism for formation of
      endogenous exhaled particles and that these particles originate from the terminal
      bronchioles.

PMID- 20056849
TI  - Rhythmic contraction generates adjustable passive stiffness in rabbit detrusor.
AB  - The length-tension (L-T) relationships in airway and vascular smooth muscles have
      been shown to adapt with length changes over time. Our prior studies have shown
      that the active and passive L-T relationships in rabbit detrusor smooth muscle
      (DSM) can adapt and that DSM exhibits adjustable passive stiffness (APS)
      characterized by a passive L-T curve that is a function of strain and activation
      history. The present study demonstrates that passive tension due to APS can
      represent a substantial fraction of total tension over a broad length range. Our
      previous studies have shown that maximal KCl-induced contractions at short muscle
      lengths generate APS that is revealed by increased pseudo-steady-state passive
      tension at longer lengths compared with previous measurements at those lengths.
      The objective of the present study was to determine the mechanisms involved in
      APS generation. Increasing the number of KCl-induced contractions or the duration
      of a contraction increased the amount of APS generated. Furthermore, a fraction
      of APS was restored in calcium-free solution and was sensitive to the general
      serine and threonine protein kinase inhibitor staurosporine. Most importantly,
      rhythmic contraction (RC) generated APS, and because RC occurs spontaneously in
      human bladder, a physiological role for RC was potentially identified.

PMID- 20056851
TI  - The role of nicotine on respiratory sensory gating measured by respiratory
      related evoked potentials.
AB  - Respiratory perception can be altered by changes in emotional or psychological
      states. This may be due to affective (i.e., anxiety) modulation of respiratory
      sensory gating. Nicotine withdrawal induces elevated anxiety and decreased
      somatosensory gating. Respiratory sensory gating is evidenced by decreased
      amplitude of the respiratory-related evoked potentials (RREP) N(1) peak for the
      second occlusion (S2) when two 150-ms occlusions are presented with a 500-ms
      interval during an inspiration. The N(1) peak amplitude ratio of the S2 and first
      occlusion (S1) (S2/S1) is <0.5 and due to central neural sensory gating. We
      hypothesized that withdrawal from nicotine is anxiogenic and reduces respiratory
      gating in smokers. The RREP was recorded in smokers with 12-h withdrawal from
      nicotine and nonsmokers using a paired occlusion protocol. In smokers, the RREP
      was measured after nicotine withdrawal, then with either nicotine or placebo gum,
      followed by the second RREP trial. Nonsmokers received only placebo gum. After
      nicotine withdrawal, the smokers had a higher state anxiety compared with
      nonsmokers. There was a significant interaction between groups (nonsmokers vs.
      smokers with nicotine vs. smokers with placebo) and test (pre- vs. posttreatment)
      in RREP N(1) peak amplitude S2/S1. The S2/S1 in the smokers were larger than in
      nonsmokers before treatment. After gum treatment, the smoker-with-placebo group
      had a significantly larger S2/S1 than the other two groups. The S2/S1 was
      significantly decreased after the administration of nicotine gum in smokers due
      to significantly decreased S2 amplitudes. The RREP N(f) and P(1) peaks were
      unaffected. These results demonstrated that respiratory sensory gating was
      decreased in smokers after nicotine withdrawal. Nicotine increased respiratory
      sensory gating in smokers with a S2/S1 similar to that of the nonsmokers.
      Nicotine did not change respiratory sensory information arrival, but secondary
      information processing in respiratory sensation.

PMID- 20056852
TI  - Carbohydrate feeding during recovery alters the skeletal muscle metabolic
      response to repeated sessions of high-intensity interval exercise in humans.
AB  - Exercise training under conditions of reduced carbohydrate (CHO) availability has
      been reported to augment gains in skeletal muscle oxidative capacity; however,
      the underlying mechanisms are unclear. We examined the effect of manipulating CHO
      intake on the acute metabolic response to high-intensity interval exercise,
      including signaling cascades linked to mitochondrial biogenesis. Ten men
      performed two trials in random order separated by >or=1 wk. Each trial consisted
      of a morning (AM) and afternoon (PM) training session (5 x 4 min cycling at
      approximately 90-95% of heart rate reserve) separated by 3 h of recovery during
      which subjects ingested a high-CHO drink (HI-HI) or nonenergetic placebo (HI-LO)
      before PM exercise. Biopsies (vastus lateralis) revealed that muscle
      phosphocreatine and ATP content were similar after AM exercise but decreased to a
      greater extent during PM exercise in HI-LO vs. HI-HI. Phosphorylation of p38
      mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK)
      increased approximately 4-fold and 2-fold, respectively, during AM exercise with
      no difference between conditions. After PM exercise, p38 MAPK phosphorylation was
      higher in HI-LO vs. HI-HI, whereas AMPK was not different between conditions.
      Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1
      alpha) gene expression increased approximately 8-fold during recovery from AM
      exercise and remained elevated during PM exercise with no differences between
      conditions. Cytochrome oxidase subunit 4 (COXIV) mRNA was also elevated 3 h after
      AM exercise, with no difference between conditions. These data provide evidence
      that p38 MAPK is a nutrient-sensitive signaling molecule that could be involved
      in the altered skeletal muscle adaptive response reported after exercise training
      under conditions of restricted CHO intake, but further research is required to
      confirm this hypothesis.

PMID- 20056853
TI  - Role(s) of gravitational loading during developing period on the growth of rat
      soleus muscle fibers.
AB  - Effects of gravitational loading or unloading on the gain of the characteristics
      in soleus muscle fibers were studied in rats. The tail suspension was performed
      in newborn rats from postnatal day 4 to month 3, and the reloading was allowed
      for 3 mo in some rats. Single expression of type I myosin heavy chain (MHC) was
      observed in approximately 82% of fibers in 3-mo-old controls, but the fibers
      expressing multiple MHC isoforms were noted in the unloaded rats. Although 97% of
      fibers in 3-mo-old controls had a single neuromuscular junction at the central
      region of fiber, fibers with multiple nerve endplates were seen in the unloaded
      group. Faster contraction speed and lower maximal tension development, even after
      normalization with fiber size, were observed in the unloaded pure type I MHC
      fibers. These parameters generally returned to the age-matched control levels
      after reloading. It was suggested that antigravity-related tonic activity plays
      an important role in the gain of single neural innervation and of slow
      contractile properties and phenotype in soleus muscle fibers.

PMID- 20056854
TI  - Axon extension occurs independently of centrosomal microtubule nucleation.
AB  - Microtubules are polymeric protein structures and components of the cytoskeleton.
      Their dynamic polymerization is important for diverse cellular functions. The
      centrosome is the classical site of microtubule nucleation and is thought to be
      essential for axon growth and neuronal differentiation--processes that require
      microtubule assembly. We found that the centrosome loses its function as a
      microtubule organizing center during development of rodent hippocampal neurons.
      Axons still extended and regenerated through acentrosomal microtubule nucleation,
      and axons continued to grow after laser ablation of the centrosome in early
      neuronal development. Thus, decentralized microtubule assembly enables axon
      extension and regeneration, and, after axon initiation, acentrosomal microtubule
      nucleation arranges the cytoskeleton, which is the source of the sophisticated
      morphology of neurons.

PMID- 20056855
TI  - A composite of multiple signals distinguishes causal variants in regions of
      positive selection.
AB  - The human genome contains hundreds of regions whose patterns of genetic variation
      indicate recent positive natural selection, yet for most the underlying gene and
      the advantageous mutation remain unknown. We developed a method, composite of
      multiple signals (CMS), that combines tests for multiple signals of selection and
      increases resolution by up to 100-fold. By applying CMS to candidate regions from
      the International Haplotype Map, we localized population-specific selective
      signals to 55 kilobases (median), identifying known and novel causal variants.
      CMS can not just identify individual loci but implicates precise variants
      selected by evolution.

PMID- 20056856
TI  - Kepler planet-detection mission: introduction and first results.
AB  - The Kepler mission was designed to determine the frequency of Earth-sized planets
      in and near the habitable zone of Sun-like stars. The habitable zone is the
      region where planetary temperatures are suitable for water to exist on a planet's
      surface. During the first 6 weeks of observations, Kepler monitored 156,000
      stars, and five new exoplanets with sizes between 0.37 and 1.6 Jupiter radii and
      orbital periods from 3.2 to 4.9 days were discovered. The density of the Neptune
      sized Kepler-4b is similar to that of Neptune and GJ 436b, even though the
      irradiation level is 800,000 times higher. Kepler-7b is one of the lowest-density
      planets (approximately 0.17 gram per cubic centimeter) yet detected. Kepler-5b, 
      6b, and -8b confirm the existence of planets with densities lower than those
      predicted for gas giant planets.

PMID- 20056858
TI  - Spreading the spirit of EMBO.

PMID- 20056859
TI  - Public health. U.S. panel favors wider use of preventive drug treatment.

PMID- 20056860
TI  - Japan. 2010 science budget not apocalyptic, as feared.

PMID- 20056857
TI  - Gamma-ray emission from the shell of supernova remnant W44 revealed by the Fermi
      LAT.
AB  - Recent observations of supernova remnants (SNRs) hint that they accelerate cosmic
      rays to energies close to ~10(15) electron volts. However, the nature of the
      particles that produce the emission remains ambiguous. We report observations of
      SNR W44 with the Fermi Large Area Telescope at energies between 2 x 10(8)
      electron volts and 3 x10(11) electron volts. The detection of a source with a
      morphology corresponding to the SNR shell implies that the emission is produced
      by particles accelerated there. The gamma-ray spectrum is well modeled with
      emission from protons and nuclei. Its steepening above approximately 10(9)
      electron volts provides a probe with which to study how particle acceleration
      responds to environmental effects such as shock propagation in dense clouds and
      how accelerated particles are released into interstellar space.

PMID- 20056861
TI  - Ecology. Europe's bats resist fungal scourge of North America.

PMID- 20056862
TI  - China. After long march, scientists create 'Chinese NIH'.

PMID- 20056865
TI  - India. Fatal fire and tritium poisoning leave nuclear labs searching for answers.

PMID- 20056866
TI  - Invasion biology. From Medfly to moth: raising a buzz of dissent.

PMID- 20056867
TI  - Invasion biology. Gaps in moth logic.

PMID- 20056868
TI  - Research institutions. Plan to merge Texas schools runs into faculty opposition.

PMID- 20056869
TI  - Materials science. Next wave of metamaterials hopes to fuel the revolution.

PMID- 20056870
TI  - Archaeology. Virtual archaeologists recreate parts of ancient worlds.

PMID- 20056872
TI  - Honing the geoengineering strategy.

PMID- 20056871
TI  - Accelerator physics. The next big beam?

PMID- 20056873
TI  - Financial conflicts of interest worth knowing.

PMID- 20056874
TI  - Incentives: stimulus missed an opportunity.

PMID- 20056875
TI  - Incentives: encouraging adventurous ideas.

PMID- 20056876
TI  - Science and regulation. Mountaintop mining consequences.

PMID- 20056877
TI  - Molecular biology. Directing the centromere guardian.

PMID- 20056878
TI  - Geochemistry. Deep mantle properties.

PMID- 20056879
TI  - Ecology. Clarity on honey bee collapse?

PMID- 20056880
TI  - Ecology. Valuing common species.

PMID- 20056881
TI  - Physics. Electron nematic phases proliferate.

PMID- 20056882
TI  - CRISPR/Cas, the immune system of bacteria and archaea.
AB  - Microbes rely on diverse defense mechanisms that allow them to withstand viral
      predation and exposure to invading nucleic acid. In many Bacteria and most
      Archaea, clustered regularly interspaced short palindromic repeats (CRISPR) form
      peculiar genetic loci, which provide acquired immunity against viruses and
      plasmids by targeting nucleic acid in a sequence-specific manner. These
      hypervariable loci take up genetic material from invasive elements and build up
      inheritable DNA-encoded immunity over time. Conversely, viruses have devised
      mutational escape strategies that allow them to circumvent the CRISPR/Cas system,
      albeit at a cost. CRISPR features may be exploited for typing purposes,
      epidemiological studies, host-virus ecological surveys, building specific
      immunity against undesirable genetic elements, and enhancing viral resistance in
      domesticated microbes.

PMID- 20056883
TI  - Punishers benefit from third-party punishment in fish.
AB  - In cases where uninvolved bystanders pay to punish defectors, this behavior has
      typically been interpreted in terms of group-level rather than individual-level
      benefits. Male cleaner fish, Labroides dimidiatus, punish their female partner if
      she cheats while inspecting model clients. Punishment promotes female cooperation
      and thereby yields direct foraging benefits to the male. Thus, third-party
      punishment can evolve via self-serving tendencies in a nonhuman species, and this
      finding may shed light on the evolutionary dynamics of more complex behavior in
      other animal species, including humans.

PMID- 20056884
TI  - Quantum criticality in an Ising chain: experimental evidence for emergent E8
      symmetry.
AB  - Quantum phase transitions take place between distinct phases of matter at zero
      temperature. Near the transition point, exotic quantum symmetries can emerge that
      govern the excitation spectrum of the system. A symmetry described by the E8 Lie
      group with a spectrum of eight particles was long predicted to appear near the
      critical point of an Ising chain. We realize this system experimentally by using
      strong transverse magnetic fields to tune the quasi-one-dimensional Ising
      ferromagnet CoNb2O6 (cobalt niobate) through its critical point. Spin excitations
      are observed to change character from pairs of kinks in the ordered phase to spin
      flips in the paramagnetic phase. Just below the critical field, the spin dynamics
      shows a fine structure with two sharp modes at low energies, in a ratio that
      approaches the golden mean predicted for the first two meson particles of the E8
      spectrum. Our results demonstrate the power of symmetry to describe complex
      quantum behaviors.

PMID- 20056885
TI  - Nematic electronic structure in the "parent" state of the iron-based
      superconductor Ca(Fe(1-x)Co(x))2As2.
AB  - The mechanism of high-temperature superconductivity in the newly discovered iron
      based superconductors is unresolved. We use spectroscopic imaging-scanning
      tunneling microscopy to study the electronic structure of a representative
      compound CaFe1.94Co0.06As2 in the "parent" state from which this
      superconductivity emerges. Static, unidirectional electronic nanostructures of
      dimension eight times the inter-iron-atom distance a(Fe-Fe) and aligned along the
      crystal a axis are observed. In contrast, the delocalized electronic states
      detectable by quasiparticle interference imaging are dispersive along the b axis
      only and are consistent with a nematic alpha2 band with an apparent band folding
      having wave vector q vector congruent with +/-2pi/8a(Fe-Fe) along the a axis. All
      these effects rotate through 90 degrees at orthorhombic twin boundaries,
      indicating that they are bulk properties. As none of these phenomena are expected
      merely due to crystal symmetry, underdoped ferropnictides may exhibit a more
      complex electronic nematic state than originally expected.

PMID- 20056886
TI  - Energy-conversion properties of vapor-liquid-solid-grown silicon wire-array
      photocathodes.
AB  - Silicon wire arrays, though attractive materials for use in photovoltaics and as
      photocathodes for hydrogen generation, have to date exhibited poor performance.
      Using a copper-catalyzed, vapor-liquid-solid-growth process, SiCl4 and BCl3 were
      used to grow ordered arrays of crystalline p-type silicon (p-Si) microwires on p+
      Si(111) substrates. When these wire arrays were used as photocathodes in contact
      with an aqueous methyl viologen(2+/+) electrolyte, energy-conversion efficiencies
      of up to 3% were observed for monochromatic 808-nanometer light at fluxes
      comparable to solar illumination, despite an external quantum yield at short
      circuit of only 0.2. Internal quantum yields were at least 0.7, demonstrating
      that the measured photocurrents were limited by light absorption in the wire
      arrays, which filled only 4% of the incident optical plane in our test devices.
      The inherent performance of these wires thus conceptually allows the development
      of efficient photovoltaic and photoelectrochemical energy-conversion devices
      based on a radial junction platform.

PMID- 20056887
TI  - E-type asteroid (2867) Steins as imaged by OSIRIS on board Rosetta.
AB  - The European Space Agency's Rosetta mission encountered the main-belt asteroid
      (2867) Steins while on its way to rendezvous with comet 67P/Churyumov
      Gerasimenko. Images taken with the OSIRIS (optical, spectroscopic, and infrared
      remote( )imaging system) cameras on board Rosetta show that Steins is an oblate
      body with an effective spherical diameter of 5.3 kilometers. Its surface does not
      show color variations. The morphology of Steins is dominated by linear faults and
      a large 2.1-kilometer-diameter crater near its south pole. Crater counts reveal a
      distinct lack of small craters. Steins is not solid rock but a rubble pile and
      has a conical appearance that is probably the result of reshaping due to
      Yarkovsky-O'Keefe-Radzievskii-Paddack (YORP) spin-up. The OSIRIS images
      constitute direct evidence for the YORP effect on a main-belt asteroid.

PMID- 20056888
TI  - Reefs as cradles of evolution and sources of biodiversity in the Phanerozoic.
AB  - Large-scale biodiversity gradients among environments and habitats are usually
      attributed to a complex array of ecological and evolutionary factors. We tested
      the evolutionary component of such gradients by compiling the environments of the
      geologically oldest occurrences of marine genera and using sampling
      standardization to assess if originations tended to be clustered in particular
      environments. Shallow, tropical environments and carbonate substrates all tend to
      have harbored high origination rates. Diversity within these environments tended
      to be preferentially generated in reefs, probably because of their habitat
      complexity. Reefs were also prolific at exporting diversity to other
      environments, which might be a consequence of low-diversity habitats being more
      susceptible to invasions.

PMID- 20056889
TI  - Topology links RNA secondary structure with global conformation, dynamics, and
      adaptation.
AB  - Thermodynamic rules that link RNA sequences to secondary structure are well
      established, but the link between secondary structure and three-dimensional
      global conformation remains poorly understood. We constructed comprehensive three
      dimensional maps depicting the orientation of A-form helices across RNA junctions
      in the Protein Data Bank and rationalized our findings with modeling and nuclear
      magnetic resonance spectroscopy. We show that the secondary structures of
      junctions encode readily computable topological constraints that accurately
      predict the three-dimensional orientation of helices across all two-way
      junctions. Our results suggest that RNA global conformation is largely defined by
      topological constraints encoded at the secondary structural level and that
      tertiary contacts and intermolecular interactions serve to stabilize specific
      conformers within the topologically allowed ensemble.

PMID- 20056890
TI  - A transient niche regulates the specification of Drosophila intestinal stem
      cells.
AB  - Stem cell niches are locations where stem cells reside and self-renew. Although
      studies have shown how niches maintain stem cell fate during tissue homeostasis,
      less is known about their roles in establishing stem cells. The adult Drosophila
      midgut is maintained by intestinal stem cells (ISCs); however, how they are
      established is unknown. Here, we show that an ISC progenitor generates a niche
      cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4
      homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated
      state and subsequently breaks down and dies, resulting in the specification of
      ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell-niche
      biology, where progenitors generate transient niches that determine stem cell
      fate and may give insights into stem cell specification in other tissues.

PMID- 20056891
TI  - Essential role of the histone methyltransferase G9a in cocaine-induced
      plasticity.
AB  - Cocaine-induced alterations in gene expression cause changes in neuronal
      morphology and behavior that may underlie cocaine addiction. In mice, we
      identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the
      lysine dimethyltransferase G9a in cocaine-induced structural and behavioral
      plasticity. Repeated cocaine administration reduced global levels of H3K9
      dimethylation in the nucleus accumbens. This reduction in histone methylation was
      mediated through the repression of G9a in this brain region, which was regulated
      by the cocaine-induced transcription factor DeltaFosB. Using conditional
      mutagenesis and viral-mediated gene transfer, we found that G9a down-regulation
      increased the dendritic spine plasticity of nucleus accumbens neurons and
      enhanced the preference for cocaine, thereby establishing a crucial role for
      histone methylation in the long-term actions of cocaine.

PMID- 20056893
TI  - Genome-wide evidence for selection acting on single amino acid repeats.
AB  - Low complexity and homopolymer sequences within coding regions are known to
      evolve rapidly. While their expansion may be deleterious, there is increasing
      evidence for a functional role associated with these amino acid sequences.
      Homopolymer sequences are thought to evolve mostly through replication slippage
      and, therefore, they may be expected to be longer in regions with relaxed
      selective constraint. Within the coding sequences of eukaryotes, alternatively
      spliced exons are known to evolve under relaxed constraints in comparison to
      those exons that are constitutively spliced because they are not included in all
      of the mature mRNA of a gene. This relaxed exposure to selection leads to faster
      rates of evolution for alternatively spliced exons in comparison to
      constitutively spliced exons. Here, we have tested the effect of splicing on the
      structure (composition, length) of homopolymer sequences in relation to the
      splicing pattern in which they are found. We observed a significant relationship
      between alternative splicing and homopolymer sequences with alternatively spliced
      genes being enriched in number and length of homopolymer sequences. We also
      observed lower codon diversity and longer homocodons, suggesting a balance
      between slippage and point mutations linked to the constraints imposed by
      selection.

PMID- 20056894
TI  - Green tea catechin EGCG inhibits ileal apical sodium bile acid transporter ASBT.
AB  - Green tea catechins exhibit hypocholesterolemic effects probably via their
      inhibitory effects on intestinal bile acid absorption. Ileal apical sodium
      dependent bile acid transporter (ASBT) is responsible for reabsorption of bile
      acids. The present studies were, therefore, designed to investigate the
      modulation of ASBT function and membrane expression by green tea catechins in
      human embryonic kidney HEK-293 cells stably transfected with ASBT-V5 fusion
      protein and intestinal Caco-2 monolayers. Our data showed that ASBT activity was
      significantly decreased by (-)-epigallocatechin-3-gallate (EGCG) but not other
      green tea catechins. Inhibition of PKC, phosphatidylinositol 3-kinase, and MAPK
      dependent pathways failed to block the reduction in ASBT activity by EGCG.
      Kinetics studies showed a significant decrease in the V(max) of the transporter,
      whereas total ASBT content on the plasma membrane was unaltered by EGCG.
      Concomitant with the decrease in ASBT function, EGCG significantly reduced ASBT
      pool in the detergent-insoluble fraction, while increasing its presence in the
      detergent-soluble fraction of plasma membrane. Furthermore, EGCG decreased the
      association of ASBT with floating lipid raft fractions of cellular membrane on
      Optiprep density gradient. In conclusion, our data demonstrate a novel role of
      lipid rafts in the modulation of ASBT function by the dietary component EGCG,
      which may underlie the hypocholesterolemic effects of green tea.

PMID- 20056895
TI  - Impact of elevation of total bilirubin level and etiology of the liver disease on
      serum N-glycosylation patterns in mice and humans.
AB  - The GlycoFibroTest and GlycoCirrhoTest are noninvasive alternatives for liver
      biopsy that can be used as a follow-up tool for fibrosis patients and to diagnose
      cirrhotic patients, respectively. These tests are based on the altered N
      glycosylation of total serum protein. Our aim was to investigate the impact of
      etiology on the alteration of N-glycosylation and whether other characteristics
      of liver patients could have an influence on N-glycosylation. In human liver
      patients, no specific alteration could be found to make a distinction according
      to etiological factor, although alcoholic patients had a significant higher mean
      value for the GlycoCirrhoTest. Undergalactosylation did not show a significantly
      different quantitative alteration in the cirrhotic and noncirrhotic population of
      all etiologies. Importantly, patients with an elevation of total bilirubin level
      (>2 mg/dl) had a strong increase of glycans modified with alpha1-6 fucose. The
      fucosylation index was therefore significantly higher in fibrosis/cirrhosis and
      hepatocellular carcinoma patients with elevated total bilirubin levels
      irrespective of etiology. Furthermore, in a multiple linear regression analysis,
      only markers for cholestasis significantly correlated with the fucosylation
      index. In mouse models of chronic liver disease, the fucosylation index was
      uniquely significantly increased in mice that were induced with a common bile
      duct ligation. Mice that were chronically injected with CCl(4) did not show this
      increase. Apart from this difference, common changes characteristic to fibrosis
      development in mice were observed. Finally, mice induced with a partial portal
      vein ligation did not show biological relevant changes indicating that portal
      hypertension does not contribute to the alteration of N-glycosylation.

PMID- 20056896
TI  - Macrophage-mediated phagocytosis of apoptotic cholangiocytes contributes to
      reversal of experimental biliary fibrosis.
AB  - Studies have suggested the reversibility of liver fibrosis, but the mechanisms of
      fibrosis reversal are poorly understood. We investigated the possible functional
      link between apoptosis, macrophages, and matrix turnover in rat liver during
      reversal of fibrosis secondary to bile duct ligation (BDL). Biliary fibrosis was
      induced by BDL for 4 wk. After Roux-en-Y (RY)-bilio-jejunal-anastomosis,
      resolution of fibrosis was monitored for up to 12 wk by hepatic collagen content,
      matrix metalloproteinase (MMP) expression and activities, and fibrosis-related
      gene expression. MMP expression and activities were studied in macrophages after
      engulfment of apoptotic cholangiocytes in vitro. Hepatic collagen decreased to
      near normal at 12 wk after RY-anastomosis. During reversal, profibrogenic mRNA
      declined, whereas expression of several profibrolytic MMPs increased. Fibrotic
      septa showed fragmentation at week 4 and disappeared at week 12. Peak
      histological remodeling at week 4 was characterized by massive apoptosis of
      cytokeratin 19+ cholangiocytes, >90% in colocalization with CD68+ macrophages,
      and a 2- to 7.5-fold increase in matrix-degrading activities. In vitro,
      phagocytosis of apoptotic cholangiocytes induced matrix-degrading activities and
      MMP-3, -8, and -9 in rat peritoneal macrophages. We concluded that reconstruction
      of bile flow after BDL leads to an orchestrated fibrolytic program that results
      in near complete reversal of advanced fibrosis. The peak of connective tissue
      remodeling and fibrolytic activity is associated with massive apoptosis of
      cholangiocytes and their phagocytic clearance by macrophages in vivo. Macrophages
      upregulate MMPs and become fibrolytic effector cells upon apoptotic cholangiocyte
      engulfment in vitro, suggesting that phagocytosis-associated MMP induction in
      macrophages significantly contributes to biliary fibrosis reversal.

PMID- 20056897
TI  - 15-deoxy-delta 12,14-prostaglandin J2 prevents inflammatory response and
      endothelial cell damage in rats with acute obstructive cholangitis.
AB  - Acute obstructive cholangitis is a common disease with a high mortality rate.
      Ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), such as
      15-deoxy-Delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), have been proposed as a
      new class of anti-inflammatory compounds. This study investigated the effect of
      15D-PGJ(2) treatment on lipopolysaccharide (LPS)-induced acute obstructive
      cholangitis. The rats were randomly assigned to five groups: sham operation
      (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion
      (Sham+Saline), sham operation with intraperitoneal LPS infusion (Sham+LPS), bile
      duct ligation (BDL) with saline infusion into the bile duct (BDL+Saline), and BDL
      with LPS infusion into the bile duct (BDL+LPS). Biochemical assays of blood
      samples, histology of the liver, portal venous pressure, hyaluronic acid
      clearance, and expression of inflammation-associated genes in the liver were
      evaluated. Furthermore, the Sham+LPS and the BDL+LPS group were divided into two
      groups (with and without 15D-PGJ(2) treatment), and their survival rates were
      compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic
      acid clearance, and expression of inflammation-associated genes in the liver were
      all significantly higher in the BDL+LPS group compared with those in the
      BDL+Saline group, indicating the presence of increased liver damage in the first
      group. However, preoperative administration of 15D-PGJ(2) significantly improved
      these outcomes. Furthermore, the survival rate after establishment of cholangitis
      was significantly improved by the administration of 15D-PGJ(2) in the BDL+LPS
      group. These results clearly demonstrate that 15D-PGJ(2) inhibits the
      inflammatory response and endothelial cell damage seen in acute obstructive
      cholangitis and could contribute to improve the outcome of this pathology.

PMID- 20056898
TI  - Transient outward potassium current in ICC.
AB  - Interstitial cells of Cajal (ICC) are the pacemakers of the gut, initiating slow
      wave activity. Several ion channels have been identified that contribute to the
      depolarization phase of the slow wave. Our aim was to contribute to knowledge
      about the identity and role of ICC potassium channels in pacemaking. Here we
      describe a transient outward potassium current in cell-attached patches of ICC.
      This current was activated almost instantaneously at potentials positive of the
      resting membrane potential and inactivated as a single exponential or
      biexponential with time constants that varied widely from patch to patch.
      Averaged traces gave a biexponential inactivation with time constants of
      approximately 40 and approximately 500 ms, with no clear voltage dependence.
      Analysis of single-channel openings and closings indicated a channel conductance
      of 5 pS and permeability sequence of K(+) (111) > Na(+) (1) > N-methyl-d
      glucamine(+) (0.11). The current was completely blocked by 20 microM clotrimazole
      but was unaffected by 20 microM ketoconazole, 10 microM E4031, or 20 microM
      clofilium; 5 mM 4-aminopyridine slowed the activation of the current. The
      transient outward current may be important in moderating the upstroke of the
      pacemaker potential.

PMID- 20056899
TI  - Variations of inflammatory mediators and alpha1-antitrypsin levels after lung
      volume reduction surgery for emphysema.
AB  - RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease
      imbalance, is responsible for declining pulmonary function and progressive
      cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and
      alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared
      with respiratory rehabilitation. METHODS: A total of 28 patients with moderate to
      severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared
      with 26 similar patients, who refused operation and followed a standardized
      rehabilitation program, and to a matched healthy group. Respiratory function,
      body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin
      levels were evaluated before and 12 months after treatment. Gene expression
      levels of inflammatory mediators and protease-antiprotease were assessed in
      emphysematous specimens from 17 operated patients by matching to normal tissue
      from resection margins. MEASUREMENTS AND MAIN RESULTS: Significant improvements
      were only obtained after surgery in respiratory function (FEV(1), +25.2%, P <
      0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for
      carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P <
      0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory
      mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P
      < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P <
      0.001). Supportive gene expression analysis demonstrated active inflammation and
      protease hyperactivity in the resected emphysematous tissue. Reduction of TNF
      alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly
      correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001,
      respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02,
      and P = 0.09, respectively). CONCLUSIONS: LVRS significantly reduced circulating
      inflammatory mediators and increased antiprotease levels over respiratory
      rehabilitation, also improving respiratory function and nutritional status.
      Correlations of inflammatory mediators and antiprotease levels with RV and,
      partly, with body composition suggest that elimination of inflammatory
      emphysematous tissue may explain clinical improvements after surgery.

PMID- 20056900
TI  - A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in
      patients with asthma.
AB  - RATIONALE: IL-4 and IL-13 share many biological functions important in the
      development of allergic airway inflammation and are implicated in the
      pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL
      4Ralpha that blocks both IL-4 and IL-13 pathways. OBJECTIVES: To evaluate
      efficacy and safety of AMG 317 in patients with moderate to severe asthma.
      METHODS: In this phase 2, randomized, double-blind, placebo-controlled study,
      patients received weekly subcutaneous injections of placebo or AMG 317 (75-300
      mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was
      change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom
      score. MEASUREMENTS AND MAIN RESULTS: Mean ACQ change (SE) was -0.49 (0.09) in
      placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317
      75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively
      (treatment effect P = 0.25). No statistically significant differences were
      observed in the secondary endpoints. Numerical decreases in number of and time to
      exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg.
      Preplanned analyses by tertile of baseline ACQ revealed that patients with higher
      baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious
      adverse events were reported in three patients, each noted as not related to
      study drug. CONCLUSIONS: AMG 317 did not demonstrate clinical efficacy across the
      overall group of patients. Clinically significant improvements were observed in
      several outcome measures in patients with higher baseline ACQ scores. AMG 317 was
      safe and well tolerated in this study population. Clinical trial registered with
      www.clinicaltrials.gov (NCT 00436670).

PMID- 20056901
TI  - Modafinil effects during acute continuous positive airway pressure withdrawal: a
      randomized crossover double-blind placebo-controlled trial.
AB  - RATIONALE: Continuous positive airway pressure (CPAP) use is associated with
      reduced motor vehicle accidents in patients with obstructive sleep apnea (OSA).
      However, interruption of CPAP therapy is common and is associated with a decline
      in daytime function. OBJECTIVES: We hypothesized that the wakefulness promoter,
      modafinil, would ameliorate this decline. METHODS: Patients were admitted to the
      laboratory for three consecutive nights. CPAP was used for the first night,
      followed by a baseline day, and was then withdrawn for the two subsequent nights
      (nasal airflow monitored). On each of the mornings after the two CPAP withdrawal
      nights, patients received 200 mg modafinil or placebo (n = 21) in a randomized,
      double-blind, crossover design. Treatment periods were separated by a 5-week
      washout. Driving simulator performance, neurocognitive performance, and
      subjective alertness were measured by the AusEd driving simulator, psychomotor
      vigilance task, and Karolinska Sleepiness Scale, respectively. MEASUREMENTS AND
      MAIN RESULTS: During CPAP withdrawal, severe sleep-disordered breathing was
      evident and administration of modafinil improved simulated driving performance
      (steering variability, P < 0.0001; mean reaction time, P <or= 0.0002; lapses, P
      <or= 0.01 on a concurrent task), psychomotor vigilance task (mean 1/reaction time
      and lapses, both P <or= 0.0002), and subjective sleepiness (P <or= 0.01).
      CONCLUSIONS: Modafinil prevented the decline in simulated driving performance,
      neurocognitive performance, and subjective sleepiness in patients with OSA with
      acutely interrupted CPAP therapy. Clinical trial registered with the Australian
      New Zealand Clinical Trials Registry at www.anzctr.org.au (ACTRN12606000027516).

PMID- 20056902
TI  - Clinical outcomes of pulmonary arterial hypertension in patients carrying an
      ACVRL1 (ALK1) mutation.
AB  - RATIONALE: Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1)
      mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and/or
      heritable pulmonary arterial hypertension (PAH). OBJECTIVES: To describe the
      characteristics of patients with PAH carrying an ACVRL1 mutation. METHODS: We
      reviewed clinical, functional, and hemodynamic characteristics of 32 patients
      with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French
      PAH Network and 23 from literature analysis. These cases were compared with 370
      patients from the French PAH Network (93 with a bone morphogenetic protein
      receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without
      identified mutation). Distribution of mutations in the ACVRL1 gene in patients
      with PAH was compared with the HHT Mutation Database. MEASUREMENTS AND MAIN
      RESULTS: At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8
      +/- 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 +/- 14.9 and 47.6
      +/- 16.3 yr, respectively; P < 0.0001). In seven of the nine patients from the
      French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation
      carriers had better hemodynamic status at diagnosis, but none responded to acute
      vasodilator challenge and they had shorter survival when compared with other
      patients with PAH despite similar use of specific therapies. ACVRL1 mutations in
      exon 10 were more frequently observed in patients with PAH, as compared with what
      was observed in the HHT Mutation Database (33.3 vs. 5%; P < 0.0001). CONCLUSIONS:
      ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis.
      Despite less severe initial hemodynamics and similar management, these patients
      had worse prognosis compared with other patients with PAH, suggesting more rapid
      disease progression.

PMID- 20056904
TI  - A review of quality of care evaluation for the palliation of dyspnea.
AB  - Assessment and management of dyspnea has emerged as a priority topic for quality
      evaluation and improvement. Evaluating dyspnea quality of care requires valid,
      reliable, and responsive measures of the care provided to patients across
      settings and diseases. As part of an Agency for Healthcare Research and Quality
      Symposium, we reviewed quality of care measures for dyspnea by compiling quality
      measures identified in systematic searches and reviews. Systematic reviews
      identified only three existing quality measurement sets that included quality
      measures for dyspnea care. The existing dyspnea quality measures reported by
      retrospective evaluations of care assess only four aspects: dyspnea assessment
      within 48 hours of hospital admission, use of objective scales to rate dyspnea
      severity, identification of management plans, and evidence of dyspnea reduction.
      To begin to improve care, clinicians need to assess and regularly document
      patient's experiences of dyspnea. There is no consensus on how dyspnea should be
      characterized for quality measurement, and although over 40 tools exist to assess
      dyspnea, no rating scale or instrument is ideal for palliative care. The panel
      recommended that dyspnea assessment should include a measure of intensity and
      some inquiry into the associated bother or distress experienced by the patient. A
      simple question into the presence or absence of dyspnea would be unlikely to help
      guide therapy, as complete relief of dyspnea in advanced disease would not be
      anticipated. Additional knowledge gaps include standards for clinical dyspnea
      care, assessment in the cognitively impaired, and evaluation of effectiveness of
      dyspnea care for patients with advanced disease.

PMID- 20056903
TI  - Clinical predictors of a diagnosis of idiopathic pulmonary fibrosis.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) and other idiopathic interstitial
      pneumonias (IIPs) have similar clinical and radiographic features, but their
      histopathology, response to therapy, and natural history differ. A surgical lung
      biopsy is often required to distinguish between these entities. OBJECTIVES: We
      sought to determine if clinical variables could predict a histopathologic
      diagnosis of IPF in patients without honeycomb change on high-resolution computed
      tomography (HRCT). METHODS: Data from 97 patients with biopsy-proven IPF and 38
      patients with other IIPs were examined. Logistic regression models were built to
      identify the clinical variables that predict histopathologic diagnosis of IPF.
      MEASUREMENTS AND MAIN RESULTS: Increasing age and average total HRCT interstitial
      score on HRCT scan of the chest may predict a biopsy confirmation of IPF. Sex,
      pulmonary function, presence of desaturation, or distance walked during a 6
      minute walk test did not help discriminate pulmonary fibrosis from other IIPs.
      CONCLUSIONS: Clinical data may be used to predict a diagnosis of IPF over other
      IIPs. Validation of these data with a prospective study is needed.

PMID- 20056905
TI  - Inhibition of urokinase activity reduces primary tumor growth and metastasis
      formation in a murine lung carcinoma model.
AB  - RATIONALE: Lung cancer is the most common malignancy in humans. Urokinase (uPA)
      plays a crucial role in carcinogenesis by facilitating tumor cell invasion and
      metastasis. OBJECTIVES: We investigated the effect of the highly specific
      urokinase inhibitor CJ-463 (benzylsulfonyl-D-Ser-Ser-4-amidinobenzylamide) on
      tumor growth, metastasis formation, and tumor vascularization in the murine Lewis
      lung carcinoma (LLC) and a human small lung cancer model. METHODS: A quantity of
      3 x 10(6) LLC cells were subcutaneously injected into the right flank of C57Bl6/N
      mice, uPA knock out, and uPA receptor knockout mice. Seven days later mice were
      randomized to receive intraperitoneally either saline (control group), CJ-463 (10
      and 100 mg/kg, twice a day), or its ineffective stereoisomer (10 mg/kg, twice a
      day). Tumor volume was measured every second day and metastasis formation was
      monitored by volumetric-computed tomography. Twelve days after onset of treatment
      mice were killed and tumors were prepared for histologic examination.
      MEASUREMENTS AND MAIN RESULTS: Treatment with CJ-463 resulted in a significant
      inhibition of primary tumor growth, with the highest efficacy seen in the 100
      mg/kg group. In addition, histological analysis of the lung revealed a
      significant reduction in lung micrometastasis in the 100 mg/kg group. Similarly,
      a reduced seeding of tumor cells into the lung after intravenous injection of LLC
      cells was observed in inhibitor-treated mice. In these mice, treatment with CJ
      463 appeared not to significantly alter the relative extent of tumor
      vascularization. In vitro, proliferation of LLC cells remained unchanged upon
      inhibitor treatment. CJ-463 was found to similarly reduce tumor growth in uPA
      receptor knockout mice, but was ineffective in uPA knockout mice. CONCLUSIONS:
      Our results suggest that synthetic low-molecular-weight uPA-inhibitors offer as
      novel agents for treatment of lung cancer.

PMID- 20056906
TI  - Forecast: [cloud].

PMID- 20056908
TI  - Plasmin triggers chemotaxis of monocyte-derived dendritic cells through an Akt2
      dependent pathway and promotes a T-helper type-1 response.
AB  - OBJECTIVE: Dendritic cells (DC) accumulate in atherosclerotic arteries where they
      can modulate atherogenesis. We investigated whether plasmin might alter the
      function of human DC. METHODS AND RESULTS: Stimulation of monocyte-derived DC
      with plasmin elicited a time-dependent actin polymerization and chemotaxis
      comparable to that triggered by the standard chemoattractant formyl-methionyl
      leucyl-phenylalanine. Plasmin triggered rapid activation of Akt and mitogen
      activated protein kinases, followed by phosphorylation of the regulatory myosin
      light chain and chemotaxis. For the chemotactic DC migration, the activation of
      Akt and p38 and extracellular signal-regulated kinase 1/2 mitogen-activated
      protein kinases were indispensable, as shown by pharmacological inhibitors. DC
      express Akt1 and Akt2, but not Akt3. However, in DC, plasmin activates
      exclusively Akt2 via a p38 mitogen-activated protein kinase-dependent pathway.
      Accordingly, knockdown of Akt2 with short-hairpin RNA, but not of Akt1, blocked
      the plasmin-induced extracellular signal-regulated kinase 1/2 activation and the
      chemotactic response. Moreover, plasmin-stimulated DC induced polarization of
      CD4(+) T cells toward the interferon-gamma-producing, proinflammatory Th1
      phenotype. Consistent with a role for DC and adaptive immune response in
      atherogenesis, we demonstrate DC in human atherosclerotic vessels and show that
      plasmin is abundant in human atherosclerotic lesions, where it colocalizes with
      DC. CONCLUSIONS: Plasmin generation in the atherosclerotic vessel wall might
      contribute to accumulation of DC, activation of the adaptive immune response, and
      aggravation of atherosclerosis.

PMID- 20056909
TI  - Propionyl-L-carnitine improves postischemic blood flow recovery and
      arteriogenetic revascularization and reduces endothelial NADPH-oxidase 4-mediated
      superoxide production.
AB  - OBJECTIVE: The beneficial effect of the natural compound propionyl-l-carnitine
      (PLC) on intermittent claudication in patients with peripheral arterial disease
      is attributed to its anaplerotic function in ischemic tissues, but inadequate
      information is available concerning action on the vasculature. METHODS AND
      RESULTS: We investigated the effects of PLC in rabbit hind limb collateral
      vessels after femoral artery excision, mouse dorsal air pouch, chicken
      chorioallantoic membrane, and vascular cells by angiographic, Doppler flow, and
      histomorphometrical and biomolecular analyses. PLC injection accelerated hind
      limb blood flow recovery after 4 days (P<0.05) and increased angiographic
      quadriceps collateral vascularization after 7 days (P<0.001) Histomorphometry
      confirmed the increased vascular area (P<0.05), with unchanged intramuscular
      capillary density. PLC-induced dilatative adaptation, and growth was found
      associated with increased inducible nitric oxide synthase and reduced arterial
      vascular endothelial growth factor and intracellular adhesion molecule-1
      expression. PLC also increased vascularization in air pouch and chorioallantoic
      membrane (P<0.05), particularly in large vessels. PLC increased endothelial and
      human umbilical vascular endothelial cell proliferation and rapidly reduced
      inducible nitric oxide synthase and NADPH-oxidase 4-mediated reactive oxygen
      species production in human umbilical vascular endothelial cells; NADPH-oxidase 4
      also regulated NF-kappaB-independent intracellular adhesion molecule-1
      expression. CONCLUSIONS: Our results provided strong evidence that PLC improves
      postischemic flow recovery and revascularization and reduces endothelial NADPH
      oxidase-related superoxide production. We recommend that PLC should be included
      among therapeutic interventions that target endothelial function.

PMID- 20056910
TI  - c-Jun N-terminal kinase primes endothelial cells at atheroprone sites for
      apoptosis.
AB  - OBJECTIVE: Atherosclerosis is a focal disease that occurs predominantly at
      branches and bends of the arterial tree. Endothelial cells (EC) at
      atherosusceptible sites are prone to injury, which can contribute to lesion
      formation, whereas EC at atheroprotected sites are resistant. The c-Jun N
      terminal kinase (JNK) is activated constitutively in EC at atherosusceptible
      sites but is inactivated at atheroprotected sites by mitogen-activated protein
      kinase phosphatase-1 (MKP-1). Here, we examined the effects of JNK activation on
      EC physiology at atherosusceptible sites. METHODS AND RESULTS: We identified
      transcriptional programs regulated by JNK by applying a specific pharmacological
      inhibitor to cultured EC and assessing the transcriptome using microarrays. This
      approach and subsequent validation by gene silencing revealed that JNK positively
      regulates the expression of numerous proapoptotic molecules. Analysis of aortae
      of wild-type, JNK1(-/-), and MKP-1(-/-) mice revealed that EC at an
      atherosusceptible site express proapoptotic proteins and are primed for apoptosis
      and proliferation in response to lipopolysaccharide through a JNK1-dependent
      mechanism, whereas EC at a protected site expressed lower levels of proapoptotic
      molecules and were protected from injury by MKP-1. CONCLUSIONS: Spatial variation
      of JNK1 activity delineates the spatial distribution of apoptosis and turnover of
      EC in arteries.

PMID- 20056911
TI  - An autocrine linkage between matrix metalloproteinase-14 and Tie-2 via ectodomain
      shedding modulates angiopoietin-1-dependent function in endothelial cells.
AB  - OBJECTIVE: The angiopoietin (Ang)-Tie-2 system plays a critical role during fetal
      and adult angiogenesis. Herein, we explored the Tie-2 shedding-related molecular
      mechanisms and the pathophysiological significance. METHODS AND RESULTS: By using
      a mouse hindlimb ischemia model, we observed dissociated expression between the
      full-length Tie-2 (fTie-2) protein and Tie-2 mRNA in thigh muscles 1 day after an
      ischemic operation, suggesting that fTie-2 expression was modified through the
      posttranscriptional regulation in vivo. A soluble form of Tie-2 produced in human
      umbilical vein endothelial cells was dramatically suppressed by treatment with
      siRNA-matrix metalloproteinase (MMP) 14 or tissue inhibitor of metalloproteinase
      3, resulting in an increase in cellular fTie-2 and thereby enhancing Ang-1
      dependent Akt phosphorylation and Akt-dependent endothelial functions, such as
      Ang-2 downregulation or an increase of endothelial viability. Phorbol-12
      myristate-13 acetate (PMA) upregulates MMP-14 mRNA via protein kinase C
      extracellular signal-regulated kinase pathways, and enhanced soluble Tie-2
      production in an MMP-14-dependent manner, resulting in a reduction of cellular
      fTie-2. In addition, the PMA-induced soluble Tie-2 was mediated by the protein
      kinase C-extracellular signal-regulated kinase signaling pathways. Finally,
      downregulation of tissue inhibitor of metalloproteinase 3 and upregulation of MMP
      14 mRNA were confirmed in ischemic thigh muscles 1 day after the operation.
      CONCLUSIONS: An autocrine linkage between the endothelial protein kinase C-MMP-14
      axis and Tie-2 shedding was shown to be a novel regulatory mechanism for the Ang
      Tie-2 system and may play a role in modulating endothelial function during
      angiogenesis.

PMID- 20056912
TI  - Metallothionein enhances angiogenesis and arteriogenesis by modulating smooth
      muscle cell and macrophage function.
AB  - OBJECTIVE: In a previous study we identified metallothionein (MT) as a candidate
      gene potentially influencing collaterogenesis. In this investigation, we
      determined the effect of MT on collaterogenesis and examined the mechanisms
      contributing to the effects we found. METHODS AND RESULTS: Collateral blood flow
      recovery was assessed using laser Doppler perfusion imaging, and angiogenesis was
      measured using a Matrigel plug assay. Smooth muscle cells were isolated from MT
      knockout (KO) mice for functional assays. Gene expression of matrix
      metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth
      factor, and Fat cadherin in smooth muscle cells was measured by real-time
      polymerase chain reaction, and protein levels of vascular endothelial growth
      factor and matrix metalloproteinase-9 were determined using enzyme-linked
      immunosorbent assay and Western blot. CD11b(+) macrophages were tested for
      invasiveness using a real-time impedance assay. Both flow recovery and
      angiogenesis were impaired in MT KO mice. Proliferation, migration, and invasion
      were decreased in MT KO smooth muscle cells, and matrix metalloproteinase-9,
      platelet-derived growth factor, and vascular endothelial growth factor expression
      were also decreased, whereas FAT-1 cadherin expression was elevated. MT KO
      CD11b(+) cells were more invasive than wild-type cells. CONCLUSIONS: MT plays an
      important role in collateral flow recovery and angiogenesis, an activity that
      appears to be mediated, in part, by the effects of MT on the functionality of 3
      cell types essential for these processes: endothelial cells, smooth muscle cells,
      and macrophages.

PMID- 20056913
TI  - Loss of the serum response factor cofactor, cysteine-rich protein 1, attenuates
      neointima formation in the mouse.
AB  - OBJECTIVE: Cysteine-rich protein (CRP) 1 and 2 are cytoskeletal lin-11 isl-1 mec
      3 (LIM)-domain proteins thought to be critical for smooth muscle differentiation.
      Loss of murine CRP2 does not overtly affect smooth muscle differentiation or
      vascular function but does exacerbate neointima formation in response to vascular
      injury. Because CRPs 1 and 2 are coexpressed in the vasculature, we hypothesize
      that CRPs 1 and 2 act redundantly in smooth muscle differentiation. METHODS AND
      RESULTS: We generated Csrp1 (gene name for CRP1) null mice by genetic ablation of
      the Csrp1 gene and found that mice lacking CRP1 are viable and fertile. Smooth
      muscle-containing tissues from Csrp1-null mice are morphologically
      indistinguishable from wild-type mice and have normal contractile properties.
      Mice lacking CRPs 1 and 2 are viable and fertile, ruling out functional
      redundancy between these 2 highly related proteins as a cause for the lack of an
      overt phenotype in the Csrp1-null mice. Csrp1-null mice challenged by wire
      induced arterial injury display reduced neointima formation, opposite to that
      seen in Csrp2-null mice, whereas Csrp1/Csrp2 double-null mice produce a wild-type
      response. CONCLUSIONS: Smooth muscle CRPs are not essential for normal smooth
      muscle differentiation during development, but may act antagonistically to
      modulate the smooth muscle response to pathophysiological stress.

PMID- 20056914
TI  - ANRIL expression is associated with atherosclerosis risk at chromosome 9p21.
AB  - OBJECTIVE: We tested the hypothesis that expression of transcripts adjacent to
      the chromosome 9p21 (Chr9p21) locus of coronary artery disease was affected by
      the genotype at this locus and associated with atherosclerosis risk. METHODS AND
      RESULTS: We replicated the locus for coronary artery disease (P=0.007; OR=1.28)
      and other manifestations of atherosclerosis such as carotid plaque (P=0.003;
      OR=1.31) in the Leipzig Heart Study, a cohort of 1134 patients with varying
      degree of angiographically assessed coronary artery disease. Expression analysis
      in peripheral blood mononuclear cells (n=1098) revealed that transcripts EU741058
      and NR_003529 of antisense noncoding RNA in the INK4 locus (ANRIL) were
      significantly increased in carriers of the risk haplotype (P=2.1x10(-12) and
      P=1.6x10(-5), respectively). In contrast, transcript DQ485454 remained
      unaffected, suggesting differential expression of ANRIL transcripts at Chr9p21.
      Results were replicated in whole blood (n=769) and atherosclerotic plaque tissue
      (n=41). Moreover, expression of ANRIL transcripts was directly correlated with
      severity of atherosclerosis (EU741058 and NR_003529; P=0.02 and P=0.001,
      respectively). No consistent association of Chr9p21 or atherosclerosis was found
      with expression of other genes such as CDKN2A, CDKN2B, C9orf53, and MTAP.
      CONCLUSIONS: Our data provide robust evidence for an association of ANRIL but not
      CDKN2A, CDKN2B, C9orf53, and MTAP, with atherosclerosis and Chr9p21 genotype in a
      large cohort.

PMID- 20056915
TI  - Protease imaging of human atheromata captures molecular information of
      atherosclerosis, complementing anatomic imaging.
AB  - OBJECTIVE: There is hope that molecular imaging can identify vulnerable
      atherosclerotic plaques. However, there is a paucity of clinical translational
      data to guide the future development of this field. Here, we cross-correlate
      cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of
      human atheromata or emboli with conventional imaging data, clinical data, and
      histopathologic data. METHODS AND RESULTS: Fifty-two patients undergoing carotid
      endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were
      studied with protease-activatable imaging probes. We show that protease-related
      fluorescent signal in carotid atheromata or in emboli closely reflects the
      pathophysiologic alterations of plaque inflammation and statin-mediated
      therapeutic effects on plaque inflammation. Inflammation-related fluorescent
      signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic
      lesions. Pathologically proven unstable plaques had high cathepsin-B-related
      fluorescent signal. The distribution patterns of the mean cathepsin-B imaging
      signals showed a difference between the symptomatic vs asymptomatic plaque
      groups. However, the degree of carotid stenosis or ultrasonographic echodensity
      was weakly correlated with the inflammatory proteolytic enzyme-related signal,
      suggesting that molecular imaging yields complimentary new information not
      available to conventional imaging. CONCLUSIONS: These results could justify and
      facilitate clinical trials to evaluate the use of protease-sensing molecular
      optical imaging in human atherosclerosis patients.

PMID- 20056917
TI  - TIMP2 deficiency accelerates adverse post-myocardial infarction remodeling
      because of enhanced MT1-MMP activity despite lack of MMP2 activation.
AB  - RATIONALE: Myocardial infarction (MI) results in remodeling of the myocardium and
      the extracellular matrix (ECM). Tissue inhibitors of metalloproteinases (TIMPs)
      are critical regulators of ECM integrity via inhibiting matrix metalloproteinases
      (MMPs). TIMP2 is highly expressed in the heart and is the only TIMP that, in
      addition to inhibiting MMPs, is required for cell surface activation of pro-MMP2.
      Hence, it is difficult to predict the function of TIMP2 as protective (MMP
      inhibiting) or harmful (MMP-activating) in heart disease. OBJECTIVE: We examined
      the role of TIMP2 in the cardiac response to MI. METHODS AND RESULTS: MI was
      induced in 11- to 12-week-old male TIMP2(-/-) and age-matched wild-type mice.
      Cardiac function was monitored by echocardiography at 1 and 4 weeks post-MI. ECM
      fibrillar structure was visualized using second harmonic generation and
      multiphoton imaging of unfixed/unstained hearts. Molecular analyses were
      performed at 3 days and 1 week post-MI on flash-frozen infarct, periinfarct, and
      noninfarct tissue. Membrane type 1 (MT1)-MMP levels and activity were measured in
      membrane protein fractions. TIMP2(-/-)-MI mice exhibited a 25% greater infarct
      expansion, markedly exacerbated left ventricular dilation (by 12%) and
      dysfunction (by 30%), and more severe inflammation compared to wild-type MI mice.
      Adverse ECM remodeling was detected by reduced density and enhanced disarray of
      fibrillar collagen in TIMP2(-/-)-MI compared to wild-type MI hearts. TIMP2
      deficiency completely abrogated MMP2 activation but markedly increased
      collagenase activity, particularly MT1-MMP activity post-MI. CONCLUSIONS: The MMP
      inhibitory function of TIMP2 is a key determinant of post-MI myocardial
      remodeling primarily because of its inhibitory action on MT1-MMP. TIMP2
      replenishment in diseased myocardium could provide a potential therapy in
      reducing or preventing disease progression.

PMID- 20056916
TI  - Reduced sox9 function promotes heart valve calcification phenotypes in vivo.
AB  - RATIONALE: Calcification of heart valve structures is the most common form of
      valvular disease and is characterized by the appearance of bone-like phenotypes
      within affected structures. Despite the clinical significance, the underlying
      etiology of disease onset and progression is largely unknown and valve
      replacement remains the most effective treatment. The SRY-related transcription
      factor Sox9 is expressed in developing and mature heart valves, and its function
      is required for expression of cartilage-associated proteins, similar to its role
      in chondrogenesis. In addition to cartilage-associated defects, mice with reduced
      sox9 function develop skeletal bone prematurely; however, the ability of sox9
      deficiency to promote ectopic osteogenic phenotypes in heart valves has not been
      examined. OBJECTIVE: This study aims to determine the role of Sox9 in maintaining
      connective tissue homeostasis in mature heart valves using in vivo and in vitro
      approaches. METHODS AND RESULTS: Using histological and molecular analyses, we
      report that, from 3 months of age, Sox9(fl/+);Col2a1-cre mice develop calcific
      lesions in heart valve leaflets associated with increased expression of bone
      related genes and activation of inflammation and matrix remodeling processes.
      Consistently, ectopic calcification is also observed following direct knockdown
      of Sox9 in heart valves in vitro. Furthermore, we show that retinoic acid
      treatment in mature heart valves is sufficient to promote calcific processes in
      vitro, which can be attenuated by Sox9 overexpression. CONCLUSIONS: This study
      provides insight into the molecular mechanisms of heart valve calcification and
      identifies reduced Sox9 function as a potential genetic basis for calcific
      valvular disease.

PMID- 20056918
TI  - Angiotensin II inhibits neuronal nitric oxide synthase activation through the
      ERK1/2-RSK signaling pathway to modulate central control of blood pressure.
AB  - RATIONALE: Angiotensin (Ang) II exerts diverse physiological actions in both the
      peripheral and central neural systems. It was reported that the activity of Ang
      II is higher in the nucleus tractus solitarii (NTS) of spontaneously hypertensive
      rats (SHRs) and that angiotensin type-1 receptors are colocalized with NAD(P)H
      oxidase in the neurons of the NTS, resulting in the induction of local reactive
      oxygen species production by Ang II. However, the signaling mechanisms of Ang II
      that induce hypertension remain unclear. OBJECTIVE: The aim of this study was to
      investigate the possible signaling pathways involved in Ang II-mediated blood
      pressure regulation in the NTS. METHODS AND RESULTS: Male SHRs were treated with
      losartan or tempol for 2 weeks, after which systolic blood pressure was observed
      to decrease significantly. Dihydroethidium staining showed many cells with high
      reactive oxygen species in the NTS of SHRs. The addition of losartan or tempol
      decreased the numbers of reactive oxygen species-positive cells in the NTS. The
      systemic administration of losartan or tempol reduced the systolic blood pressure
      and increased NO production. Immunoblotting and immunohistochemical analysis
      further showed that inhibition of Ang II activity by losartan or tempol
      significantly increased the expression extracellular signal-regulated kinase
      (ERK)1/2, ribosomal protein S6 kinase (RSK), and also increased neuronal NO
      synthase (nNOS) phosphorylation. RSK was also found to bind directly to nNOS and
      induce phosphorylation at the Ser1416 position. CONCLUSIONS: Taken together,
      these results suggest that the ERK1/2-RSK-nNOS signaling pathway may play a
      significant role in Ang II-mediated central blood pressure regulation.

PMID- 20056919
TI  - Involvement of phosphoinositide 3-kinase gamma in angiogenesis and healing of
      experimental myocardial infarction in mice.
AB  - RATIONALE: Phosphoinositide 3-kinase (PI3K)gamma is expressed in hematopoietic
      cells, endothelial cells (ECs), and cardiomyocytes and regulates different
      cellular functions relevant to inflammation, tissue remodeling and cicatrization.
      Recently, PI3Kgamma inhibitors have been indicated for the treatment of chronic
      inflammatory/autoimmune diseases and atherosclerosis. OBJECTIVE: We aimed to
      determine PI3Kgamma contribution to the angiogenic capacity of ECs and the effect
      of PI3Kgamma inhibition on healing of myocardial infarction (MI). METHODS AND
      RESULTS: Human umbilical ECs were treated with a selective PI3Kgamma inhibitor,
      AS605240, or a pan-phosphoinositide 3-kinases inhibitor, LY294002. Both
      inhibitory treatments and small interfering RNA-mediated PI3Kgamma knockdown
      strongly impaired ECs angiogenic capacity, because of suppression of the PI3K/Akt
      and mitogen-activated protein kinase pathways. Constitutive activation of Akt
      rescued the angiogenic defect. Reparative angiogenesis was studied in vivo in a
      model of MI. AS605240 did not affect MI-induced PI3Kgamma upregulation, whereas
      it suppressed Akt activation and downstream signaling. AS605240 strongly reduced
      inflammation, enhanced cardiomyocyte apoptosis, and impaired survival and
      proliferation of ECs in peri-infarct zone, which resulted in defective reparative
      neovascularization. As a consequence, AS605240-treated MI hearts showed increased
      infarct size and impaired recovery of left ventricular function. Similarly,
      PI3Kgamma-deficient mice showed impaired reparative neovascularization, enhanced
      cardiomyocyte apoptosis and marked deterioration of cardiac function following
      MI. Mice expressing catalytically inactive PI3Kgamma also failed to mount a
      proper neovascularization, although cardiac dysfunction was similar to wild-type
      controls. CONCLUSIONS: PI3Kgamma expression and catalytic activity are involved
      at different levels in reparative neovascularization and healing of MI.

PMID- 20056920
TI  - Uncoupling protein-2 modulates myocardial excitation-contraction coupling.
AB  - RATIONALE: Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein
      that is expressed in mammalian myocardium under normal conditions and upregulated
      in pathological states such as heart failure. UCP2 is thought to protect
      cardiomyocytes against oxidative stress by dissipating the mitochondrial proton
      gradient and mitochondrial membrane potential (DeltaPsi(m)), thereby reducing
      mitochondrial reactive oxygen species generation. However, in apparent conflict
      with its uncoupling role, UCP2 has also been proposed to be essential for
      mitochondrial Ca(2+) uptake, which could have a protective action by stimulating
      mitochondrial ATP production. OBJECTIVE: The goal of this study was to better
      understand the role of myocardial UCP2 by examining the effects of UCP2 on
      bioenergetics, Ca(2+) homeostasis, and excitation-contraction coupling in
      neonatal cardiomyocytes. METHODS AND RESULTS: Adenoviral-mediated expression of
      UCP2 caused a mild depression of DeltaPsi(m) and increased the basal rate of
      oxygen consumption but did not affect total cellular ATP levels. Mitochondrial
      Ca(2+) uptake was examined in permeabilized cells loaded with the mitochondria
      selective Ca(2+) probe, rhod-2. UCP2 overexpression markedly inhibited
      mitochondrial Ca(2+) uptake. Pretreatment with the UCP2-specific inhibitor
      genipin largely reversed the effects UCP2 expression on mitochondrial Ca(2+)
      handling, bioenergetics, and oxygen utilization. Electrically evoked cytosolic
      Ca(2+) transients and spontaneous cytosolic Ca(2+) sparks were examined using
      fluo-based probes and confocal microscopy in line scan mode. UCP2 overexpression
      significantly prolonged the decay phase of [Ca(2+)](c) transients in electrically
      paced cells, increased [Ca(2+)](c) spark activity and increased the probability
      that Ca(2+) sparks propagated into Ca(2+) waves. This dysregulation results from
      a loss of the ability of mitochondria to suppress local Ca(2+)-induced Ca(2+)
      release activity of the sarcoplasmic reticulum. CONCLUSION: Increases in UCP2
      expression that lower DeltaPsi(m) and contribute to protection against oxidative
      stress, also have deleterious effects on beat-to-beat [Ca(2+)](c) handling and
      excitation-contraction coupling, which may contribute to the progression of heart
      disease.

PMID- 20056921
TI  - FTY720 stimulates 27-hydroxycholesterol production and confers atheroprotective
      effects in human primary macrophages.
AB  - RATIONALE: The synthetic sphingosine analog FTY720 is undergoing clinical trials
      as an immunomodulatory compound, acting primarily via sphingosine 1-phosphate
      receptor activation. Sphingolipid and cholesterol homeostasis are closely
      connected but whether FTY720 affects atherogenesis in humans is not known.
      OBJECTIVE: We examined the effects of FTY720 on the processing of scavenged
      lipoprotein cholesterol in human primary monocyte-derived macrophages. METHODS
      AND RESULTS: FTY720 did not affect cholesterol uptake but inhibited its delivery
      to the endoplasmic reticulum, reducing cellular free cholesterol cytotoxicity.
      This was accompanied by increased levels of Niemann-Pick C1 protein (NPC1) and
      ATP-binding cassette transporter (ABC)A1 proteins and increased efflux of
      endosomal cholesterol to apolipoprotein A-I. These effects were not dependent on
      sphingosine 1-phosphate receptor activation. Instead, FTY720 stimulated the
      production of 27-hydroxycholesterol, an endogenous ligand of the liver X
      receptor, leading to liver X receptor-induced upregulation of ABCA1.
      Fluorescently labeled FTY720 was targeted to late endosomes, and the FTY720
      induced upregulation of ABCA1 was NPC1-dependent, but the endosomal exit of
      FTY720 itself was not. CONCLUSIONS: We conclude that FTY720 decreases cholesterol
      toxicity in primary human macrophages by reducing the delivery of scavenged
      lipoprotein cholesterol to the endoplasmic reticulum and facilitating its release
      to physiological extracellular acceptors. Furthermore, FTY720 stimulates 27
      hydroxycholesterol production, providing an explanation for the atheroprotective
      effects and identifying a novel mechanism by which FTY720 modulates signaling.

PMID- 20056922
TI  - CaMKII-dependent diastolic SR Ca2+ leak and elevated diastolic Ca2+ levels in
      right atrial myocardium of patients with atrial fibrillation.
AB  - RATIONALE: Although research suggests that diastolic Ca(2+) levels might be
      increased in atrial fibrillation (AF), this hypothesis has never been tested.
      Diastolic Ca(2+) leak from the sarcoplasmic reticulum (SR) might increase
      diastolic Ca(2+) levels and play a role in triggering or maintaining AF by
      transient inward currents through Na(+)/Ca(2+) exchange. In ventricular
      myocardium, ryanodine receptor type 2 (RyR2) phosphorylation by Ca(2+)/calmodulin
      dependent protein kinase (CaMK)II is emerging as an important mechanism for SR
      Ca(2+) leak. OBJECTIVE: We tested the hypothesis that CaMKII-dependent diastolic
      SR Ca(2+) leak and elevated diastolic Ca(2+) levels occurs in atrial myocardium
      of patients with AF. METHODS AND RESULTS: We used isolated human right atrial
      myocytes from patients with AF versus sinus rhythm and found CaMKII expression to
      be increased by 40+/-14% (P<0.05), as well as CaMKII phosphorylation by 33+/-12%
      (P<0.05). This was accompanied by a significantly increased RyR2 phosphorylation
      at the CaMKII site (Ser2814) by 110+/-53%. Furthermore, cytosolic Ca(2+) levels
      were elevated during diastole (229+/-20 versus 164+/-8 nmol/L, P<0.05). Most
      likely, this resulted from an increased SR Ca(2+) leak in AF (P<0.05), which was
      not attributable to higher SR Ca(2+) load. Tetracaine experiments confirmed that
      SR Ca(2+) leak through RyR2 leads to the elevated diastolic Ca(2+) level. CaMKII
      inhibition normalized SR Ca(2+) leak and cytosolic Ca(2+) levels without changes
      in L-type Ca(2+) current. CONCLUSION: Increased CaMKII-dependent phosphorylation
      of RyR2 leads to increased SR Ca(2+) leak in human AF, causing elevated cytosolic
      Ca(2+) levels, thereby providing a potential arrhythmogenic substrate that could
      trigger or maintain AF.

PMID- 20056923
TI  - Vascular care in patients with Alzheimer disease with cerebrovascular lesions
      slows progression of white matter lesions on MRI: the evaluation of vascular care
      in Alzheimer's disease (EVA) study.
AB  - BACKGROUND AND PURPOSE: White matter lesions (WMLs) and cerebral infarcts are
      common findings in Alzheimer disease and may contribute to dementia severity.
      WMLs and lacunar infarcts may provide a potential target for intervention
      strategies. This study assessed whether multicomponent vascular care in patients
      with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and
      prevents occurrence of new infarcts. METHODS: A randomized controlled clinical
      trial, including 123 subjects, compared vascular care with standard care in
      patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression
      of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were
      semiquantitatively scored after 2-year follow-up. RESULTS: Sixty-five subjects
      (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58
      subjects, a follow-up scan could not be obtained due to advanced dementia or
      death. Subjects in the vascular care group had less progression of WMLs as
      measured with the WML change score (1.4 versus 2.3, P=0.03). There was no
      difference in the number of new lacunes or change in global cortical atrophy or
      medial temporal lobe atrophy between the 2 groups. CONCLUSIONS: Vascular care in
      patients with Alzheimer disease with cerebrovascular lesions slows progression of
      WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer
      disease may be beneficial, possibly in an even earlier stage of the disease.

PMID- 20056924
TI  - The relationship between waist circumference and the risk of stroke and
      myocardial infarction in a Japanese urban cohort: the Suita study.
AB  - BACKGROUND AND PURPOSE: Body mass index is most commonly used as the obesity
      index. Recently, waist circumference (WC) has been shown to be associated with
      the risk of cardiovascular disease (CVD). However, no studies have observed an
      association between WC and CVD in Japan. We examined the relationships of WC and
      body mass index with CVD in a Japanese urban population. METHODS: We studied 5474
      Japanese individuals (aged 30 to 79 years without CVD at baseline) who completed
      a baseline survey and received follow-up through December 2005. WC was measured
      at the umbilical level of participants in the standing position to the nearest 1
      cm. The Cox proportional hazard ratios for CVD according to the quartiles of WC
      were calculated after adjustment for age, smoking, and drinking status. RESULTS:
      During a mean follow-up of 11.7 years, 207 strokes and 133 myocardial infarctions
      were documented. In women, compared with the lowest quartile (WC <70 cm), the
      hazard ratio (95% CIs) after adjusting for age, smoking, and drinking in the
      highest quartile (WC >or=84 cm) were 1.85 (1.03 to 3.31) for CVD and 2.64 (1.16
      to 6.03) for stroke. However, no such relationships of WC with CVD or stroke risk
      were observed in men. After further adjustment of hypertension, diabetes, and
      hypercholesterolemia, all of the mentioned relationships were not statistically
      significant. No associations of body mass index with CVD or strokes were
      observed. CONCLUSIONS: WC may be a better predictor for CVD or stroke in Japanese
      women.

PMID- 20056925
TI  - Comparison of bone marrow stromal cells derived from stroke and normal rats for
      stroke treatment.
AB  - BACKGROUND AND PURPOSE: We compared the effect of treatment of stroke with bone
      marrow stromal cells from stroke rats (Isch-BMSC) and normal rats (Nor-BMSC) on
      functional outcome. METHODS: Isch-BMSCs and Nor-BMSCs were intravenously injected
      into rats 24 hours after middle cerebral artery occlusion. To test the mechanism
      of Isch-BMSC-enhanced neurorestoration, Isch-BMSC and Nor-BMSC cultures were
      used. RESULTS: Isch-BMSC significantly promoted functional outcome and enhanced
      angiogenesis, arterial density, and axonal regeneration compared with Nor-BMSC
      treatment animals. Isch-BMSCs exhibited increased Angiopoietin-1, Tie2, basic
      fibroblast growth factor, glial cell-derived neurotrophic factor, vascular
      endothelial growth factor, and Flk1 gene expression compared with Nor-BMSC. Using
      transwell coculture of BMSCs with brain-derived endothelial cells, Isch-BMSCs
      increased phosphorylated-Tie2 activity in brain-derived endothelial cells and
      enhanced brain-derived endothelial cells capillary tube formation compared with
      Nor-BMSCs. Inhibition of Tie2 gene expression in brain-derived endothelial cells
      using siRNA significantly attenuated BMSC-induced capillary tube formation.
      CONCLUSIONS: These data suggest that Isch-BMSCs are superior to Nor-BMSCs for the
      neurorestorative treatment of stroke, which may be mediated by the enhanced
      trophic factor and angiogenic characteristics of Isch-BMSCs.

PMID- 20056926
TI  - Sinking skin flap syndrome and paradoxical herniation after hemicraniectomy for
      malignant hemispheric infarction.
AB  - BACKGROUND AND PURPOSE: "Sinking skin flap" (SSF) syndrome is a rare complication
      after large craniectomy that may progress to "paradoxical" herniation as a
      consequence of atmospheric pressure exceeding intracranial pressure. The
      prevalence and characteristics of SSF syndrome after hemicraniectomy for
      malignant infarction of the middle cerebral artery are not well known. METHODS:
      We analyzed a prospective cohort of 27 patients who underwent hemicraniectomy for
      malignant middle cerebral artery infarction. All had a clinical and brain imaging
      follow-up at 3 months and were followed until cranioplasty. RESULTS: Three of 27
      patients (11%) had, at 3 to 5 months posthemicraniectomy, SSF syndrome with
      severe orthostatic headache as the main symptom. In addition, 4 patients (15%)
      had radiological SSF syndrome but no clinical symptoms except partial seizures in
      one. Patients with SSF syndrome had a smaller surface of craniectomy (76.2 cm(2)
      versus 88.7 cm(2), P=0.05) and a tendency toward larger infarct volume, an older
      age, and a longer delay to cranioplasty than those without this syndrome.
      CONCLUSIONS: SSF syndrome either clinically symptomatic or asymptomatic affects
      one fourth of patients 3 to 5 months after hemicraniectomy for malignant middle
      cerebral artery infarction. It should be diagnosed as early as possible to avoid
      progression to a paradoxical herniation.

PMID- 20056927
TI  - An imbalance between CD36 and ABCA1 protein expression favors lipid accumulation
      in stroke-prone ulcerated carotid plaques.
AB  - BACKGROUND: CD36 is a macrophage scavenger receptor mediating the uptake of
      modified lipoproteins, whereas the ABCA1 transporter counteracts this effect by
      mediating cellular lipid efflux. Based on a DNA microarray, we previously found
      that the CD36 and ABCA1 genes were overexpressed in symptom-causing carotid
      plaques (CP) compared with nonsymptom-causing CP. To evaluate their role in CP
      destabilization, we conducted detailed immunohistochemical studies on the
      localization of lipids, CD36 and ABCA1 proteins, extravasated red blood cells,
      and atheromatous/necrotic tissue. METHODS: Ninety-two high-grade (>70%) stenosing
      CP obtained from carotid endarterectomy were Oil-red-O-stained for evaluation of
      neutral lipids. Subgroups of nonsymptom-causing and symptom-causing CP (n=42)
      were further analyzed by immunostaining adjacent histological sections against
      CD36 and ABCA1 and examining them microscopically. RESULTS: When compared with
      nonsymptom-causing CP, the amount of extracellular lipid and the expression of
      CD36 protein were elevated in symptom-causing CP, but no difference was found in
      ABCA1 expression. These observations were also confirmed when ulcerated and
      nonulcerated CP were compared. In ulcerated CP, CD36 protein expression was
      higher than that of ABCA1, and the opposite was true in nonulcerated CP. CD36
      colocalized with extravasated red blood cells and atheromatous or necrotic areas
      in the various types of CP. CONCLUSIONS: Our results suggest that an imbalance
      between lipid influx (CD36) and efflux (ABCA1) favors lipid accumulation in
      macrophages of ulcerated CP, thus contributing to plaque destabilization.
      Furthermore, colocalization of CD36 protein with red blood cells suggests that
      intraplaque hemorrhages may contribute to the lipid load and thus the stability
      of CP.

PMID- 20056928
TI  - Assessment and improvement of figures to visually convey benefit and risk of
      stroke thrombolysis.
AB  - BACKGROUND AND PURPOSE: Deciding whether to use intravenous fibrinolytic therapy
      for acute cerebral ischemia within 3 hours of onset is challenging for patients,
      family members, and health care providers. Visual displays can permit individuals
      to rapidly understand response patterns to therapy. This study sought to
      evaluate, refine, and improve existing visual aids for stroke fibrinolytic
      decision-making. METHODS: Existing visual aids were identified by Medline search
      and querying of national guideline organizations, pharmaceutical manufacturers,
      and stroke specialists, and were rated on a formal 8-point quality rating scale
      (0, lowest; 8, highest). Based on available instruments, new visual displays were
      developed to improve informed decision-making in routine practice. RESULTS: Two
      existing visual aids were identified, one from an emergency medicine society and
      one from a pharmaceutical company. Both were comparison visual displays of
      outcomes with and without treatment; no decision matrix visual aid was found.
      Both scored 4.0 on the quality scale, showing defects of effect size distortion,
      privileging less salient outcomes, dissimilar representation by treatment group,
      and limited stakeholder participation in generation. Revised versions of these
      graphics were developed with higher quality scores (6.75 and 7.75). In addition,
      a new decision matrix display with quality score 8.0 was developed that
      complements the numeric text of a national patient education tool developed
      jointly by US neurology, emergency medicine, and stroke patient organizations.
      CONCLUSIONS: Existing visual aids for stroke fibrinolysis decision-making have
      deficiencies. New visual displays are now available to convey the health benefits
      and risks of fibrinolytic stroke therapy efficiently and informatively to
      patients and family members.

PMID- 20056929
TI  - A telestroke network enhances recruitment into acute stroke clinical trials.
AB  - BACKGROUND AND PURPOSE: Acute stroke clinical trials are conducted primarily at
      academic medical centers. As a result, patients living in rural areas are
      excluded from participation, results may not be generalizable to nonacademic
      settings, and studies may be slow to recruit subjects. Telemedicine can provide
      rural patients with emergency neurovascular consultation. We sought to determine
      whether telemedicine facilitates enrollment into acute stroke trials. METHODS: We
      have an established rural "hub and spoke" telestroke network. From 2005 to 2009,
      we participated in 2 time-sensitive acute stroke trials: Factor Seven for Acute
      Hemorrhagic Stroke and Minocycline to Improve Neurological Outcome. Candidates
      for the 2 trials could be identified at either the hub or at the spokes, with
      patients presenting to the latter transferred to the hub for enrollment. We
      analyzed the times from symptom onset to consultation via telemedicine, arrival
      at the hub, and to initiation of a study drug to determine the impact of
      telemedicine on study enrollment. RESULTS: Nineteen of 28 subjects enrolled in
      the 2 trials were identified initially at an outside facility via a telemedicine
      link. An additional 9 candidates identified by telemedicine could not be enrolled
      because of transportation time. Arrival at the hub was 127 minutes later (median,
      207 [95% CI, 145 to 255] versus 80 [95% CI, 55 to 142]; P=0.0002), and study drug
      was started 74 minutes later (median, 298 [95% CI, 218 to 352] versus 225 [95%
      CI, 147 to 330]; P=0.05) for subjects who were identified via telemedicine and
      required transport to the hub compared with local subjects who presented directly
      to the hub. CONCLUSIONS: Telemedicine can enhance enrollment into time-sensitive
      acute stroke trials. However, transfer of subjects to the hub results in delays
      in study initiation for some and precludes enrollment for others similar to the
      weaknesses of "ship and drip" thrombolytic strategies. To save time, efforts are
      needed to enroll clinical trial subjects and begin the research drug at the
      remote site under telemedicine guidance.

PMID- 20056930
TI  - Enlarged perivascular spaces on MRI are a feature of cerebral small vessel
      disease.
AB  - BACKGROUND AND PURPOSE: Enlarged perivascular spaces in the brain are common but
      generally overlooked and of uncertain pathophysiology. They may reflect
      underlying cerebral small vessel disease. We determined whether enlarged
      perivascular spaces were associated with lacunar stroke subtype and white matter
      hyperintensities, markers of established small vessel disease. MATERIALS AND
      METHODS: We prospectively recruited patients with acute ischemic lacunar or
      cortical stroke. Age-matched nonstroke control subjects were also recruited. We
      rated basal ganglia and centrum semiovale enlarged perivascular spaces 0 to 4
      (0=none, 4=>40) on T2-weighted MRI and white matter hyperintensities. We compared
      enlarged perivascular spaces between stroke subtypes and control subjects and
      assessed associations with vascular risk factors and white matter
      hyperintensities. RESULTS: We recruited 350 patients; 129 lacunar, 124 cortical
      stroke, and 97 age-matched control subjects. Adjusting for vascular risk factors
      and white matter hyperintensities, total enlarged perivascular spaces were
      associated with lacunar stroke subtype (P=0.04) in the acute stroke group
      (n=253); basal ganglia enlarged perivascular spaces were associated with lacunar
      stroke subtype (P=0.003), deep (P=0.02) and periventricular white matter
      hyperintensities (P=0.01); in all 350 subjects, total enlarged perivascular
      spaces were associated with deep (P<0.001) and periventricular (P<0.001) white
      matter hyperintensities. CONCLUSIONS: Although prevalent in patients with
      vascular risk factors and stroke, enlarged perivascular spaces are specifically
      associated with lacunar ischemic stroke and white matter hyperintensities.
      Further studies should determine the mechanism of this association while
      including adequate controls to account for stroke and vascular risk factors.
      Enlarged perivascular spaces should not be overlooked in studies of small vessel
      disease.

PMID- 20056931
TI  - The benefits of intravenous thrombolysis relate to the site of baseline arterial
      occlusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET).
AB  - BACKGROUND AND PURPOSE: In ischemic stroke, the site of arterial obstruction has
      been shown to influence recanalization and clinical outcomes. However, this has
      not been studied in randomized controlled trials, nor has the impact of arterial
      obstruction site on reperfusion and infarct growth been assessed. We studied the
      influence of site and degree of arterial obstruction patients enrolled in the
      Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). METHODS: EPITHET was
      a prospective, randomized, placebo-controlled trial of intravenous tissue
      plasminogen activator (tPA) in the 3- to 6-hour time window. Arterial obstruction
      site and degree were rated on magnetic resonance angiography blinded to treatment
      allocation and outcomes. RESULTS: In 101 EPITHET patients, 87 had adequate
      quality magnetic resonance angiography, of whom 54 had baseline arterial
      obstruction. Infarct growth attenuation was greater in those with tPA treatment
      compared to placebo among patients with middle cerebral artery (MCA) obstruction
      (P=0.037). The treatment benefit of tPA over placebo in attenuating infarct
      growth was greater for MCA than internal carotid artery (ICA) obstruction
      (P=0.060). With tPA treatment, good clinical outcome was more likely with MCA
      than with ICA obstruction (P=0.005). Most patients with ICA obstruction did not
      achieve good clinical outcome, whether treated with tPA (100%) or placebo (77%).
      The study was underpowered to prove any treatment benefit of tPA among patients
      with any or severe degree of arterial obstruction. CONCLUSIONS: Arterial
      obstruction site strongly predicts outcomes. ICA obstruction carries a uniformly
      poor prognosis, whereas good outcomes with MCA obstruction are associated with
      tPA therapy.

PMID- 20056932
TI  - Prediction of recurrent stroke and vascular death in patients with transient
      ischemic attack or nondisabling stroke: a prospective comparison of validated
      prognostic scores.
AB  - BACKGROUND AND PURPOSE: Several predictive scores have been developed and
      validated for stratifying cerebrovascular patients based on the risk of future
      (cerebro)vascular events. We aimed to prospectively compare the predictive
      accuracy of the Essen Stroke Risk Score, Stroke Prognostic Instrument, Hankey
      score, and the Life Long After Cerebral ischemia score. METHODS: Between August
      2005 and December 2006, we included 2381 patients from 10 German stroke centers
      with an acute nondisabling ischemic stroke or transient ischemic attack and with
      prospective assessment of clinical variables for calculation of the predictive
      scores. A total of 1897 patients (79.7%) could be followed up for a median of 1
      year. To evaluate the performance of each model, we calculated the area under the
      curve by receiver operating characteristic. In addition, we used the recommended
      cutoff values for calculation of sensitivity and specificity for stroke or the
      combined outcome of stroke or cardiovascular death. RESULTS: The Kaplan-Meier
      estimate for the overall annual stroke risk was 4.8% and for recurrent stroke or
      cardiovascular death 6.6%. We could confirm the predictive value of all 4
      previously developed scores with a marginally superior performance of the SPI-II.
      CONCLUSIONS: In patients with acute nondisabling ischemic stroke or transient
      ischemic attack, all 4 scores are able to stratify the risk of recurrent stroke
      or the combined outcome. Simple point scores (Essen Stroke Risk Score, Stroke
      Prognostic Instrument) may help to raise awareness for medical prevention in
      clinical routine and increase compliance with risk factor modification.

PMID- 20056933
TI  - Safety of intravenous thrombolysis for acute ischemic stroke in patients
      receiving antiplatelet therapy at stroke onset.
AB  - BACKGROUND AND PURPOSE: Antiplatelets (APs) may increase the risk of symptomatic
      intracerebral hemorrhage (ICH) following intravenous thrombolysis after ischemic
      stroke. METHODS: We assessed the safety of thrombolysis under APs in 11,865
      patients compliant with the European license criteria and recorded between 2002
      and 2007 in the Safe Implementation of Treatments in Stroke (SITS) International
      Stroke Thrombolysis Register (SITS-ISTR). Outcome measures of univariable and
      multivariable analyses included symptomatic ICH (SICH) per SITS Monitoring Study
      (SITS-MOST [deterioration in National Institutes of Health Stroke Scale >or=4
      plus ICH type 2 within 24 hours]), per European Cooperative Acute Stroke Study II
      (ECASS II [deterioration in National Institutes of Health Stroke Scale >or=4 plus
      any ICH]), functional outcome at 3 months and mortality. RESULTS: A total of 3782
      (31.9%) patients had received 1 or 2 AP drugs at baseline: 3016 (25.4%)
      acetylsalicylic acid (ASA), 243 (2.0%) clopidogrel, 175 (1.5%) ASA and
      dipyridamole, 151 (1.3%) ASA and clopidogrel, and 197 (1.7%) others. Patients
      receiving APs were 5 years older and had more risk factors than AP naive
      patients. Incidences of SICH per SITS-MOST (ECASS II respectively) were as
      follows: 1.1% (4.1%) AP naive, 2.5% (6.2%) any AP, 2.5% (5.9%) ASA, 1.7% (4.2%)
      clopidogrel, 2.3% (5.9%) ASA and dipyridamole, and 4.1% (13.4%) ASA and
      clopidogrel. In multivariable analyses, the combination of ASA and clopidogrel
      was associated with increased risk for SICH per ECASS II (odds ratio, 2.11; 95%
      CI, 1.29 to 3.45; P=0.003). However, we found no significant increase in the risk
      for mortality or poor functional outcome, irrespective of the AP subgroup or SICH
      definition. CONCLUSIONS: The absolute excess of SICH of 1.4% (2.1%) in the pooled
      AP group is small compared with the benefit of thrombolysis seen in randomized
      trials. Although caution is warranted in patients receiving the combination of
      ASA and clopidogrel, AP treatment should not be considered a contraindication to
      thrombolysis.

PMID- 20056937
TI  - The "natural selection" of muscle for cardiac repair.

PMID- 20056938
TI  - Career moves: induced pluripotent cells from human aortic smooth muscle cells can
      efficiently redifferentiate into parental phenotype.

PMID- 20056939
TI  - NEMO nuances NF-kappaB.

PMID- 20056940
TI  - S100A12 links to thoracic aortic aneurysms.

PMID- 20056941
TI  - The role of microRNA-133 in cardiac hypertrophy uncovered.

PMID- 20056942
TI  - Introduction to cardiotoxicity review series.

PMID- 20056943
TI  - Molecular mechanisms of cardiovascular toxicity of targeted cancer therapeutics.
AB  - In 2002, Hoshijima and Chien drew largely theoretical parallels between the
      dysregulation of the signaling pathways driving cancer and those driving cardiac
      hypertrophy (Hoshijima M, Chien KR. J Clin Invest. 2002;109:849-855). On the
      surface, this statement appeared to stretch the limits of reason, given the fact
      that cancer cells are known for their proliferative capacity, and adult
      cardiomyocytes are, except under unusual circumstances, terminally differentiated
      and incapable of re-entering the cell cycle. However, on closer examination,
      there are numerous parallels between signaling pathways that drive tumorigenesis
      and signaling pathways that regulate hypertrophic responses and survival in
      cardiomyocytes. Indeed, this issue appears to be at the core of the
      cardiotoxicity (often manifest as a dilated cardiomyopathy) that can result from
      treatment with agents typically referred to as "targeted therapeutics," which
      target specific protein kinases that are dysregulated in cancer. Herein, we
      examine the cardiotoxicity of targeted therapeutics, focusing on the underlying
      molecular mechanisms, thereby allowing an understanding of the problem but also
      allowing the identification of novel, and sometimes surprising, roles played by
      protein kinases in the heart.

PMID- 20056944
TI  - The vulnerability of the heart as a pluricellular paracrine organ: lessons from
      unexpected triggers of heart failure in targeted ErbB2 anticancer therapy.
AB  - In this review, we address clinical aspects and mechanisms of ventricular
      dysfunction induced by anticancer drugs targeted to the ErbB2 receptor. ErbB2
      antagonists prolong survival in cancer, but also interfere with homeostatic
      processes in the heart. ErbB2 is a coreceptor for ErbB4, which is activated by
      neuregulin-1. This epidermal growth factor-like growth factor is released from
      endothelial cells in the endocardium and in the myocardial microcirculation,
      hence contributing to intercellular crosstalk in the ventricle. We look at the
      physiological aspects of neuregulin-1/ErbB signaling in the ventricle, and review
      its (mal)adaptive responses in chronic heart failure. We also compare structural
      aspects of ErbB receptor activation in cancer and cardiac cells, and analyze the
      mode of action of current ErbB2 antagonists. This allows us to predict how these
      drugs interfere with paracrine processes in the ventricle. Differences in the
      mode of action of individual ErbB2 antagonists affect their impact on the
      function of the ventricle, considered to be "on-target" or "off-target."
      Establishing the relation between the cardiac side effects of ErbB2 antagonists
      and their impact on paracrine ventricular control mechanisms may direct the
      design of a next generation of ErbB2 inhibitors. For cardiologists, there are
      lessons to be learned from the unexpected side effects of ErbB2-targeted cancer
      therapy. The vulnerability of the heart as a pluricellular paracrine system
      appears greater than anticipated and intercellular crosstalk an essential
      component of its functional and structural integrity.

PMID- 20056947
TI  - Circadian proteins and genotoxic stress response.
AB  - The circadian clock is an evolutionarily conserved time-keeping system that
      coordinates the physiology of the organism with daily changes in the environment.
      A growing body of evidence gradually leads to the conception that virtually all
      aspects of the biochemical, physiological, and behavioral functions of the animal
      are linked to circadian regulation. Moreover, proper synchronization of various
      processes through the activity of circadian components is important for the well
      being of many organisms, including humans. The focus of this review is the
      circadian control of an organism's response to genotoxic stress, which is a major
      contributor to life-threatening human pathologies such as cancer and
      cardiovascular disease.

PMID- 20056946
TI  - The impact of macrophage insulin resistance on advanced atherosclerotic plaque
      progression.
AB  - Atherothrombotic vascular disease is the major cause of death and disability in
      obese and diabetic subjects with insulin resistance. Although increased systemic
      risk factors in the setting of insulin resistance contribute to this problem, it
      is likely exacerbated by direct effects of insulin resistance on the arterial
      wall cells that participate in atherosclerosis. A critical process in the
      progression of subclinical atherosclerotic lesions to clinically relevant lesions
      is necrotic breakdown of plaques. Plaque necrosis, which is particularly
      prominent in the lesions of diabetics, is caused by the combination of macrophage
      apoptosis and defective phagocytic clearance, or efferocytosis, of the apoptotic
      macrophages. One cause of macrophage apoptosis in advanced plaques is activation
      of a proapoptotic branch of the unfolded protein response, which is an
      endoplasmic reticulum stress pathway. Macrophages have a functional insulin
      receptor signaling pathway, and downregulation of this pathway in the setting
      insulin resistance enhances unfolded protein response-induced apoptosis.
      Moreover, other aspects of the obesity/insulin-resistance syndrome may adversely
      affect efferocytosis. These processes may therefore provide an important
      mechanistic link among insulin resistance, plaque necrosis, and atherothrombotic
      vascular disease and suggest novel therapeutic approaches to this expanding
      health problem.

PMID- 20056945
TI  - Intramyocardial fibroblast myocyte communication.
AB  - Cardiac fibroblasts are emerging as key components of normal cardiac function, as
      well as the response to stressors and injury. These most numerous cells of the
      heart interact with myocytes via paracrine mechanisms, alterations in
      extracellular matrix homeostasis, and direct cell-cell interactions. It is
      possible that they are a contributor to the inability of adult myocytes to
      proliferate and may influence cardiac progenitor biology. Furthering our
      understanding of how cardiac fibroblasts and myocytes interact may provide an
      avenue to novel treatments for heart failure prevention. This review discusses
      the most recent concepts in cardiac fibroblast-myocyte communication and areas of
      potential future research.

PMID- 20056948
TI  - Prevalence and predictors of abnormal cardiovascular responses to exercise
      testing among individuals with type 2 diabetes: the Look AHEAD (Action for Health
      in Diabetes) study.
AB  - OBJECTIVE: We examined maximal graded exercise test (GXT) results in 5,783
      overweight/obese men and women, aged 45-76 years, with type 2 diabetes, who were
      entering the Look AHEAD (Action for Health in Diabetes) study, to determine the
      prevalence and correlates of exercise-induced cardiac abnormalities. RESEARCH
      DESIGN AND METHODS: Participants underwent symptom-limited maximal GXTs.
      Questionnaires and physical examinations were used to determine demographic,
      anthropometric, metabolic, and health status predictors of abnormal GXT results,
      which were defined as an ST segment depression > or =1.0 mm, ventricular
      arrhythmia, angina pectoris, poor postexercise heart rate recovery (<22 bpm
      reduction 2 min after exercise), or maximal exercise capacity less than 5.0 METs.
      Systolic blood pressure response to exercise was examined as a continuous
      variable, without a threshold to define abnormality. RESULTS: Exercise-induced
      abnormalities were present in 1,303 (22.5%) participants, of which 693 (12.0%)
      consisted of impaired exercise capacity. ST segment depression occurred in 440
      (7.6%), abnormal heart rate recovery in 206 (5.0%), angina in 63 (1.1%), and
      arrhythmia in 41 (0.7%). Of potential predictors, only greater age was associated
      with increased prevalence of all abnormalities. Other predictors were associated
      with some, but not all, abnormalities. Systolic blood pressure response decreased
      with greater age, duration of diabetes, and history of cardiovascular disease.
      CONCLUSIONS: We found a high rate of abnormal GXT results despite careful
      screening for cardiovascular disease symptoms. In this cohort of overweight and
      obese individuals with type 2 diabetes, greater age most consistently predicted
      abnormal GXT. Long-term follow-up of these participants will show whether these
      abnormalities are clinically significant.

PMID- 20056949
TI  - A single nucleotide polymorphism in KCNQ1 is associated with susceptibility to
      diabetic nephropathy in japanese subjects with type 2 diabetes.
AB  - OBJECTIVE: Genetic factors have been considered to contribute to the development
      and progression of diabetic nephropathy. The KCNQ1 gene (potassium voltage-gated
      channel, KQT-like subfamily, member 1) was originally identified as a strong
      susceptibility gene for type 2 diabetes in two Japanese genome-wide association
      studies. In this study, we examined the association of single nucleotide
      polymorphisms (SNPs) within KCNQ1 with diabetic nephropathy in Japanese subjects
      with type 2 diabetes. RESEARCH DESIGN AND METHODS: We genotyped 33 SNPs in KCNQ1
      using 754 type 2 diabetic patients with overt nephropathy and 558 control
      subjects (an initial study), and we further examined the association of a
      candidate SNP using three other independent Japanese populations (replications 1
      3). RESULTS: We found that five SNPs were nominally associated with diabetic
      nephropathy, and the association of rs2237897 was the strongest. We also found
      that the T allele frequencies of rs2237897 were consistently higher in the
      nephropathy groups than in the control groups for all study populations (initial
      study: 0.33 vs. 0.27; replication 1: 0.32 vs. 0.30; replication 2: 0.33 vs. 0.28;
      and replication 3: 0.32 vs. 0.28), although the individual associations did not
      reach statistically significant levels. Combined analysis by a meta-analysis
      revealed that the T allele of rs2237897 was significantly associated with
      susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes
      (odds ratio 1.22 [95% CI 1.10-1.34], P = 3.1 x 10(-4), corrected P = 0.01).
      CONCLUSIONS: These results suggest that KCNQ1 is a new candidate gene for
      conferring susceptibility to diabetic nephropathy.

PMID- 20056950
TI  - Costs and consequences associated with newer medications for glycemic control in
      type 2 diabetes.
AB  - OBJECTIVE: Newer medications offer more options for glycemic control in type 2
      diabetes. However, they come at considerable costs. We undertook a health
      economic analysis to better understand the value of adding two newer medications
      (exenatide and sitagliptin) as second-line therapy to glycemic control strategies
      for patients with new-onset diabetes. RESEARCH DESIGN AND METHODS: We performed a
      cost-effectiveness analysis for the U.S. population aged 25-64. A lifetime
      analytic horizon and health care system perspective were used. Costs and quality
      adjusted life years (QALYs) were discounted at 3% annually, and costs are
      presented in 2008 U.S. dollars. We compared three glycemic control strategies: 1)
      glyburide as a second-line agent, 2) exenatide as a second-line agent, and 3)
      sitagliptin as a second-line agent. Outcome measures included QALYs gained,
      incremental costs, and the incremental cost-effectiveness ratio associated with
      each strategy. RESULTS: Exenatide and sitagliptin conferred 0.09 and 0.12
      additional QALYs, respectively, relative to glyburide as second-line therapy. In
      base case analysis, exenatide was dominated (cost more and provided fewer QALYs
      than the next most expensive option), and sitagliptin was associated with an
      incremental cost-effectiveness ratio of 169,572 dollars per QALY saved. Results
      were sensitive to assumptions regarding medication costs, side effect duration,
      and side effect-associated disutilities. CONCLUSIONS: Exenatide and sitagliptin
      may confer substantial costs to health care systems. Demonstrated gains in
      quality and/or quantity of life are necessary for these agents to provide
      economic value to patients and health care systems.

PMID- 20056951
TI  - Intergenerational cardiovascular disease risk factors involve both maternal and
      paternal BMI.
AB  - OBJECTIVE: To examine the association between parental BMI and offspring
      cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS: The study
      comprised 940 children (9.5 +/- 0.4 years) and 873 adolescents (15.5 +/- 0.5
      years). Parental weight and height were reported by the mother and the father,
      and BMI was calculated. CVD risk factors included total (sum of five skinfolds)
      and central (waist circumference) body fat, blood pressure, cardiorespiratory
      fitness, insulin sensitivity, total cholesterol, HDL cholesterol, triglycerides,
      and fibrinogen. RESULTS: Maternal and paternal BMI were positively associated
      with total and central fatness in offspring (P < 0.001). BMIs of both parents
      were significantly related to fibrinogen levels (P < 0.02), but these
      associations disappeared when controlling for fatness. There was a positive
      relationship between maternal and paternal BMI and waist circumference in the
      offspring regardless of total adiposity and height (P < 0.001). Maternal BMI was
      negatively associated with offspring cardiorespiratory fitness independently of
      fatness (P < 0.02). These relationships persisted when overweight descendants
      were excluded from the analysis. There were no significant associations between
      parental BMI and the other CVD risk factors. CONCLUSIONS: Both maternal and
      paternal BMI increase CVD risk factors of their offspring, characterized by total
      and central body fat, and higher maternal BMI was associated with poorer
      cardiorespiratory fitness. Our findings give further support to the concept that
      adiposity in parents transmits susceptibility to CVD risk to descendants, which
      is detectable even in the absence of overweight in offspring.

PMID- 20056952
TI  - Age at development of type 1 diabetes- and celiac disease-associated antibodies
      and clinical disease in genetically susceptible children observed from birth.
AB  - OBJECTIVE: To compare the ages and sequence in which antibodies associated with
      type 1 diabetes and celiac disease appear and overt diseases develop in children
      with an HLA-conferred susceptibility to both diseases. RESEARCH DESIGN AND
      METHODS: We observed 2,052 children carrying genetic risks for both type 1
      diabetes and celiac disease from birth until the median age of 5.7 years and
      analyzed diabetes- and celiac disease-associated antibodies in serum samples
      collected at 3- to 12-month intervals. Diabetes was confirmed by World Health
      Organization criteria and celiac disease by duodenal biopsies. RESULTS:
      Altogether 342 children seroconverted to positivity for at least one diabetes
      associated autoantibody and 88 to positivity for at least one celiac disease
      associated antibody at the median ages of 3.0 and 1.5 years, respectively (P <
      0.001). If only children with biochemically defined diabetes-associated
      autoantibodies against insulin, GAD, or IA-2A protein (n = 146) and children with
      tissue transglutaminase autoantibodies were compared (n = 86), the median
      seroconversion ages were 2.5 and 3.0 years (P = 0.011). Fifty-one children
      progressed to overt diabetes at 4.5 years and 44 children to celiac disease at
      4.3 years (P = 0.257). Of the 19 children who developed both diabetes- and celiac
      disease-associated antibodies, 3 progressed to both diabetes and celiac disease.
      CONCLUSIONS: Children with HLA-conferred susceptibility to type 1 diabetes and
      celiac disease develop celiac disease-associated antibodies mostly at a younger
      age or the same age at which they develop diabetes-associated autoantibodies.
      Clinical diabetes and celiac disease are commonly diagnosed at the same median
      age.

PMID- 20056953
TI  - Exploring a cancer biomarker: the example of C-reactive protein.

PMID- 20056954
TI  - Increasing the effectiveness of tobacco quitlines.

PMID- 20056955
TI  - C-reactive protein and the risk of cancer: a mendelian randomization study.
AB  - Elevated plasma levels of C-reactive protein (CRP), a marker of inflammation, are
      associated with an increased risk of cancer, but it is unclear whether this
      association is causal. We examined whether four common single-nucleotide
      polymorphisms (SNPs) in the CRP gene that are associated with altered plasma CRP
      levels are causally associated with an increased risk of cancer. The study
      population included participants in a prospective study (n = 10 215) and a cross
      sectional study (n = 36 403) of the adult general population in Denmark, all of
      whom were genotyped for the CRP SNPs. The association between plasma CRP levels
      measured by a high-sensitivity turbidimetry assay and the risk of cancer was
      examined for 8224 participants in the prospective study. The hazard ratio of
      cancer for a doubling of the plasma CRP level was 1.09 (95% confidence interval
      [CI] = 1.03 to 1.14). The nine most common genotype combinations of the four CRP
      SNPs were associated with up to a 72% increase (95% CI = 58% to 87%) in CRP
      levels but not with an increased risk of cancer. The estimated causal odds ratio
      for cancer associated with a genetically induced doubling in CRP level was 0.94
      (95% CI = 0.81 to 1.08). This finding suggests that elevated CRP levels do not
      cause cancer.

PMID- 20056956
TI  - When is cancer care cost-effective? A systematic overview of cost-utility
      analyses in oncology.
AB  - New cancer treatments pose a substantial financial burden on health-care systems,
      insurers, patients, and society. Cost-utility analyses (CUAs) of cancer-related
      interventions have received increased attention in the medical literature and are
      being used to inform reimbursement decisions in many health-care systems. We
      identified and reviewed 242 cancer-related CUAs published through 2007 and
      included in the Tufts Medical Center Cost-Effectiveness Analysis Registry
      (www.cearegistry.org). Leading cancer types studied were breast (36% of studies),
      colorectal (12%), and hematologic cancers (10%). Studies have examined
      interventions for tertiary prevention (73% of studies), secondary prevention
      (19%), and primary prevention (8%). We present league tables by disease
      categories that consist of a description of the intervention, its comparator, the
      target population, and the incremental cost-effectiveness ratio. The median
      reported incremental cost-effectiveness ratios (in 2008 US $) were $27,000 for
      breast cancer, $22,000 for colorectal cancer, $34,500 for prostate cancer,
      $32,000 for lung cancer, and $48,000 for hematologic cancers. The results
      highlight the many opportunities for efficient investment in cancer care across
      different cancer types and interventions and the many investments that are
      inefficient. Because we found only modest improvement in the quality of studies,
      we suggest that journals provide specific guidance for reporting CUA and assure
      that authors adhere to guidelines for conducting and reporting economic
      evaluations.

PMID- 20056959
TI  - WHO: the world's most powerful international organisation?

PMID- 20056958
TI  - The use of transesophageal echocardiography for placement of apicoaortic conduit
      in a patient with a porcelain aorta.

PMID- 20056957
TI  - Randomized trial: Quitline specialist training in gain-framed vs standard-care
      messages for smoking cessation.
AB  - BACKGROUND: Smoking accounts for a large proportion of cancer-related mortality,
      creating a need for better smoking cessation efforts. We investigated whether
      gain-framed messages (ie, presenting benefits of quitting) will be a more
      persuasive method to encourage smoking cessation than standard-care messages (ie,
      presenting both costs of smoking [loss-framed] and benefits of quitting).
      METHODS: Twenty-eight specialists working at the New York State Smokers' Quitline
      (a free telephone-based smoking cessation service) were randomly assigned to
      provide gain-framed or standard-care counseling and print materials. Smokers (n =
      2032) who called the New York State Smokers' Quitline between March 10, 2008, and
      June 13, 2008, were exposed to either gain-framed (n = 810) or standard-care (n =
      1222) messages, and all medically eligible callers received nicotine replacement
      therapy. A subset of 400 call recordings was coded to assess treatment fidelity.
      All treated smokers were contacted for 2-week and 3-month follow-up interviews.
      All statistical tests were two-sided. RESULTS: Specialists providing gain-framed
      counseling used gain-framed statements statistically significantly more
      frequently than those providing standard-care counseling as assessed with
      frequency ratings for the two types of gain-framed statements, achieving benefits
      and avoiding negative consequences (for achieving benefits, gain-framed mean
      frequency rating = 3.9 vs standard-care mean frequency rating = 1.4; mean
      difference = -2.5; 95% confidence interval [CI] = -2.8 to -2.3; P < .001; for
      avoiding negative consequences, gain-framed mean frequency rating = 1.5 vs
      standard-card mean frequency rating = 1.0; mean difference = -0.5; 95% CI = -0.6
      to -0.3; P < .001). Gain-framed counseling was associated with a statistically
      significantly higher rate of abstinence at the 2-week follow-up (ie, 99 [23.3%]
      of the 424 in the gain-framed group vs 76 [12.6%] of the 603 in the standard-care
      group, P < .001) but not at the 3-month follow-up (ie, 148 [28.4%] of the 522 in
      the gain-framed group vs 202 [26.6%] of the 760 in the standard-care group, P =
      .48). CONCLUSIONS: Quitline specialists can be trained to provide gain-framed
      counseling with good fidelity. Also, gain-framed messages appear to be somewhat
      more persuasive than standard-care messages in promoting early success in smoking
      cessation.

PMID- 20056960
TI  - The G20 and the three global crises: what prospects for global health?

PMID- 20056961
TI  - Communicating to citizens the benefits, harms and risks of preventive
      interventions.

PMID- 20056962
TI  - Assessing the effectiveness of human papillomavirus (HPV) vaccination to prevent
      cervical cancer: perspectives from Germany.

PMID- 20056963
TI  - Connecting the dots: the power of words and the diversity of epidemiological
      information.
AB  - Almost 30 years ago, my career in public health sciences detoured along an
      uncommon pathway: I became a wordsmith, finding unambiguous words and phrases to
      define the concepts, methods and procedures of epidemiology and related sciences.
      Playing with words made me well known among epidemiologists, a curious outcome
      because my contributions are otherwise minor. This shows how important words are.

PMID- 20056964
TI  - Adherence and chemoprevention in major cardiovascular disease: a simulation study
      of the benefits of additional use of statins.
AB  - BACKGROUND: In everyday practice, adherence to preventive medication for
      cardiovascular disease (CVD) is lower than in clinical trials and appears to
      decline to approximately 50% by about 5 years. The UK body for the evaluation of
      health technologies, NICE, currently recommends that persons with a >20% 10-year
      risk of incident cardiovascular disease receive statins. METHODS: Publications on
      adherence to statin medication in clinical trials and in normal practice were
      systematically reviewed. Data on CVD-free members of a large southern hemisphere
      cohort study were used to simulate the expected benefits of contrasting
      strategies to increase the use of statins. Risks of incident CVD and death from
      CVD were estimated. RESULTS: A strategy to enhance statin adherence among cohort
      members meeting NICE statin-prescribing guidelines resulted in about twice as
      large a reduction in the aggregate risk of CVD death as did a strategy to lower
      treatment thresholds. CONCLUSIONS: The benefits from increased spending on statin
      medication will be much greater if they result from enhanced adherence rather
      than from lowering the medication threshold.

PMID- 20056965
TI  - Health information and advocacy for "Health in All Policies": a research agenda.
AB  - Placing health in the agendas of all policy makers remains a challenge. Finding
      new ways to boost Health in All Policies should be a continuous process.
      Currently, health information initiatives gather core health statistics,
      indicators related to healthcare, along with individual level risk factors such
      as smoking or obesity. However, there is a lack of identifiable information
      showing the effect of non-primary health policies on population health. A
      research agenda is proposed, focusing on three related areas that would frame
      health information in such a way that the implications for decision-makers from
      non-health sectors are clear: (a) research in order to provide solid and
      quantitative evidence linking the social and environmental determinants of health
      with their ultimate health outcomes; (b) research that shows and quantifies the
      effect of policies and specific interventions on these determinants; and (c) the
      development of policy-linked indicators which provide a quantitative estimate of
      the health that would be gained (or disease burden that could be avoided) by
      adoption of a specific policy.

PMID- 20056966
TI  - Survival disparities in Indigenous and non-Indigenous New Zealanders with colon
      cancer: the role of patient comorbidity, treatment and health service factors.
AB  - BACKGROUND: Ethnic disparities in cancer survival have been documented in many
      populations and cancer types. The causes of these inequalities are not well
      understood but may include disease and patient characteristics, treatment
      differences and health service factors. Survival was compared in a cohort of
      Maori (Indigenous) and non-Maori New Zealanders with colon cancer, and the
      contribution of demographics, disease characteristics, patient comorbidity,
      treatment and healthcare factors to survival disparities was assessed. METHODS:
      Maori patients diagnosed as having colon cancer between 1996 and 2003 were
      identified from the New Zealand Cancer Registry and compared with a randomly
      selected sample of non-Maori patients. Clinical and outcome data were obtained
      from medical records, pathology reports and the national mortality database.
      Cancer-specific survival was examined using Kaplan-Meier survival curves and Cox
      hazards modelling with multivariable adjustment. RESULTS: 301 Maori and 328 non
      Maori patients with colon cancer were compared. Maori had a significantly poorer
      cancer survival than non-Maori (hazard ratio (HR)=1.33, 95% CI 1.03 to 1.71) that
      was not explained by demographic or disease characteristics. The most important
      factors contributing to poorer survival in Maori were patient comorbidity and
      markers of healthcare access, each of which accounted for around a third of the
      survival disparity. The final model accounted for almost all the survival
      disparity between Maori and non-Maori patients (HR=1.07, 95% CI 0.77 to 1.47).
      CONCLUSION: Higher patient comorbidity and poorer access and quality of cancer
      care are both important explanations for worse survival in Maori compared with
      non-Maori New Zealanders with colon cancer.

PMID- 20056967
TI  - Outdoor air pollution and uncontrolled asthma in the San Joaquin Valley,
      California.
AB  - BACKGROUND: The San Joaquin Valley (SJV) in California ranks among the worst in
      the USA in terms of air quality, and its residents report some of the highest
      rates of asthma symptoms and asthma-related emergency department (ED) visits and
      hospitalisations in California. Using California Health Interview Survey data,
      the authors examined associations between air pollution and asthma morbidity in
      this region. METHODS: Eligible subjects were SJV residents (2001 California
      Health Interview Survey) who reported physician-diagnosed asthma (n=1502, 14.6%).
      The authors considered two outcomes indicative of uncontrolled asthma: (1) daily
      or weekly asthma symptoms and (2) asthma-related ED visits or hospitalisation in
      the past year. Based on residential zip code, subjects were assigned annual
      average concentrations of ozone, PM(10) and PM(2.5) for the 1-year period prior
      to the interview date from their closest government air monitoring station within
      an 8 km (5 miles) radius. RESULTS: Adjusting for age, gender, race/ethnicity,
      poverty level and insurance status, the authors observed increased odds of
      experiencing daily or weekly asthma symptoms for ozone, PM(10) and PM(2.5)
      (OR(ozone) 1.23, 95% CI 0.94 to 1.60 per 10 ppb; OR(PM10) 1.29, 95% CI 1.05 to
      1.57 per 10 microg/m(3); and OR(PM2.5) 1.82; 95% CI 1.11 to 2.98 per 10
      microg/m(3)). The authors also observed increased odds of asthma-related ED
      visits or hospitalisations for ozone (OR 1.49, 95% CI 1.05 to 2.11 per 10 ppb)
      and a 29% increase in odds for PM(10) (OR 1.29, 95% CI 0.99 to 1.69 per 10
      microg/m(3)). CONCLUSIONS: Overall, these findings suggest that individuals with
      asthma living in areas of the SJV with high ozone and particulate pollution
      levels are more likely to have frequent asthma symptoms and asthma-related ED
      visits and hospitalisations.

PMID- 20056968
TI  - Time trends in childhood and adolescent obesity in England from 1995 to 2007 and
      projections of prevalence to 2015.
AB  - BACKGROUND: The aim was to examine the 1995-2007 childhood and adolescent obesity
      trends and project prevalence to 2015 by age group and social class. METHODS:
      Participants were children aged 2-10 and adolescents aged 11-18 years from
      general population households in England studied using repeated cross-sectional
      surveys. Obesity was computed using international standards. Prevalence
      projections to 2015 were based on extrapolation of linear and non-linear trends.
      RESULTS: Obesity prevalence increased from 1995 to 2007 from 3.1% to 6.9% among
      boys, and 5.2% to 7.4% among girls. There are signs of a levelling off trend past
      2004/5. Assuming a linear trend, the 2015 projected obesity prevalence is 10.1%
      (95% CI 7.5 to 12.6) in boys and 8.9% (5.8 to 12.1) in girls, and 8.0% (4.5,
      11.5) in male and 9.7% (6.0, 13.3) in female adolescents. Projected prevalence in
      manual social classes is markedly higher than in non-manual classes [boys: 10.7%
      (6.6 to 14.9) vs 7.9% (3.7 to 12.1); girls: 11.2% (7.0 to 15.3) vs 5.4% (1.3 to
      9.4); male adolescents: 10.0% (5.2 to 14.8) vs 6.7% (3.4 to 10.0); female
      adolescents: 10.4% (5.0 to 15.8) vs 8.3% (4.3 to 12.4)]. CONCLUSION: If the
      trends in young obesity continue, the percentage and numbers of obese young
      people in England will increase considerably by 2015 and the existing obesity gap
      between manual and non-manual classes will widen further. This highlights the
      need for public health action to reverse recent trends and narrow social
      inequalities in health.

PMID- 20056969
TI  - Combined effect of resting heart rate and physical activity on ischaemic heart
      disease: mortality follow-up in a population study (the HUNT study, Norway).
AB  - BACKGROUND: The combined effect of resting heart rate (RHR) and physical activity
      (PA) on ischaemic heart disease (IHD) has never been assessed. The objective of
      this study was to assess the association of RHR with IHD mortality, and to
      evaluate the potentially modifying effect of PA on this association. METHODS: In
      a prospective cohort study of 24 999 men and 25 089 women free from
      cardiovascular disease at baseline, Cox proportional hazard models were used to
      estimate adjusted hazard ratios of death from IHD related to RHR measured at
      baseline. The combined effect of RHR and self-reported PA on the risk of death
      from IHD was also assessed. RESULTS: During a mean of 18.2 (SD 4) years of follow
      up, 2566 men and 1814 women died from cardiovascular causes. For each increment
      of 10 heart beats per minute, risk of death from IHD was 18% higher in women <70
      years of age (p<0.001); no such association was observed among women > or =70
      years. Among men, there was a corresponding 10% higher risk in the younger (p =
      0.004), and 11% higher risk in the older age group (p = 0.01). Among women, the
      risk associated with high RHR was substantially attenuated in those who reported
      a high level of PA, whereas in men, there was no clear indication that PA could
      modify the positive effect of RHR. CONCLUSION: RHR is positively associated with
      the risk of death from IHD, and among women, the results suggest that by engaging
      in PA, the risk associated with a high RHR may be substantially reduced.

PMID- 20056970
TI  - Initial behavioural and attitudinal responses to influenza A, H1N1 ('swine flu').

PMID- 20056971
TI  - Community mobilisation and empowerment for combating a pandemic.

PMID- 20056972
TI  - Peritoneal dialysis after nonrenal solid organ transplantation: clinical outcomes
      and practical considerations.
AB  - The incidence of end-stage renal disease following nonrenal solid organ
      transplantation (NRSOT) is increasing and is associated with a poor prognosis.
      The etiology of end-stage renal disease is multifactorial, with calcineurin
      inhibitor (CNI) nephrotoxicity being primarily responsible. The impact of
      dialysis modality on the survival of these patients remains unclear. Peritoneal
      dialysis appears to be a feasible and safe option for renal replacement therapy
      in NRSOT patients. Concerns that NRSOT patients are at a higher risk of
      infectious and noninfectious complications necessitate practical considerations
      when prescribing and planning for peritoneal dialysis in these patients. While
      nephrotoxicity is a well-recognized complication of long-term CNI use,
      "peritoneotoxic" effects with significant alterations in peritoneal membrane
      structure and function have recently been described. Further study including the
      role of CNI-free immunotherapy protocols to optimize the outcomes of NRSOT
      recipients is needed.

PMID- 20056973
TI  - Hydrothorax: pleural effusion associated with peritoneal dialysis.
AB  - Hydrothorax in a patient treated with peritoneal dialysis (PD) poses a diagnostic
      dilemma. Hydrothorax due to migration of dialysis fluid across the diaphragm and
      into the pleural space creates a serious complication of PD but generally does
      not threaten life. Shortness of breath causes the patient to seek medical
      attention. A sudden diminution in dialysis adequacy or poor ultrafiltration rate
      constitutes a unique marker for patients treated with PD compared to the general
      population. This article reviews the etiology for hydrothorax specifically in the
      PD population. Thoracentesis with chemical analysis of the fluid, imaging studies
      with and without contrast or markers, and video-assisted thoracoscopic surgery
      play important roles in the evaluation of hydrothorax. A conservative PD regimen,
      surgical intervention, and pleurodesis provide treatment options to those
      receiving PD.

PMID- 20056974
TI  - Description of an outbreak of acute sterile peritonitis in Iran.
AB  - BACKGROUND: Outbreaks of sterile or chemical peritonitis are uncommon and often
      not well documented. It is therefore important to describe the characteristics of
      sterile peritonitis in continuous peritoneal dialysis (PD) patients. METHODS:
      Characteristics of acute chemical peritonitis (ACP) are described in 20 patients
      (5 males, 15 females; mean age 50 +/- 15 years; range 29 - 72 years). Cultures
      and Gram stains were negative for micro-organisms. All patients with symptoms of
      peritonitis were using glucose bags with the same lot number and resolution of
      peritonitis occurred only after changing the suspicious bags. The first
      measurements of dialysate-to-plasma creatinine (D/P creat) and glomerular
      filtration rate (GFR) before and after ACP were compared in 14 patients with no
      separate episode of bacterial peritonitis during that time. RESULTS: Cloudy
      dialysate was observed in 19 patients and 13 experienced abdominal pain. Mean
      dialysate white blood cell count and percentage neutrophils were 520/mm(3) (range
      100 - 1600/mm(3)) and 65% (range 14% - 98%) respectively. Analysis of the unused
      PD solution showed that endotoxin (0.06 endotoxin unit/mL), 5-hydroxymethyl
      furaldehyde (8 microg/mL), and acetaldehyde (0.4 microg/mL) concentrations were
      within acceptable ranges. In 14 patients without episodes of bacterial
      peritonitis, D/P creat was significantly higher after than before ACP (0.77 +/-
      0.07 vs 0.55 +/- 0.1, p = 0.036), whereas GFR was not (4.5 +/- 2.9 vs 4.9 +/-
      2.53 mL/minute, p = 0.62). CONCLUSION: Although chemical peritonitis in glucose
      based PD solution is uncommon, it should be distinguished from bacterial
      peritonitis in outbreaks of peritonitis. Facilities to measure glucose
      degradation products are required, especially in developing countries. Acute
      chemical peritonitis increases small-molecule transport in the short term.

PMID- 20056975
TI  - Peritoneal dialysis in Africa.
AB  - BACKGROUND: Africa is the world's second-largest and second most populous
      continent. It is also the poorest and most underdeveloped continent. Struggling
      to provide the essential health interventions for its occupants, the majority of
      African countries cannot regard renal replacement therapy a health priority.
      REVIEW: In 2007, Africa's dialysis population constituted only 4.5% of the
      world's dialysis population, with a prevalence of 74 per million population
      (pmp), compared to a global average of 250 pmp. In almost half the African
      countries, no dialysis patients are reported. The prevalence of peritoneal
      dialysis (PD) was 2.2 pmp, compared to a global prevalence of 27 pmp, with the
      bulk of African PD patients (85%) residing in South Africa. In North African
      countries, which serve 93% of the African dialysis population, the contribution
      of PD to dialysis is only 0% - 3%. Cost is a major factor affecting the provision
      of dialysis treatment and many countries are forced to ration dialysis therapy.
      Rural setting, difficult transportation, low electrification rates, limited
      access to improved sanitation and improved water sources, unsuitable living
      circumstances, and the limited number of nephrologists are obstacles to the
      provision of PD in many countries. CONCLUSION: The potential for successful
      regular PD programs in tropical countries has now been well established. Cost is
      a major prohibitive factor but the role of domestic manufacture in facilitating
      widespread use of PD is evidenced by the South African example. Education and
      training are direly needed and these are areas where international societies can
      be of great help.

PMID- 20056976
TI  - Predictors of long-term survival on peritoneal dialysis in South India: a
      multicenter study.
AB  - BACKGROUND: Little is known about survival on peritoneal dialysis (PD) in Indian
      patients since the initiation of continuous ambulatory PD (CAPD) in India in
      1991. Survival data from single centers with small numbers have been published.
      OBJECTIVE: A retrospective 4-center analysis for predictors of survival >3 years
      in south Indian chronic PD patients. METHODS: A total of 309 patients were
      trained during the observation period (from 1999 to 2004) and were analyzed in a
      multicenter study (4 centers), including 150 patients (male:female 109:41) that
      survived > or = 3 years and 59 patients that did not survive > or = 3 years
      (nonsurvivors; male: female 43:16) that were taken as controls. The patients were
      on chronic PD, predominantly CAPD, using double-bag disconnect systems. They were
      supervised by 4 nephrologists. Mean age in the nonsurvival group was 56.6 +/-
      10.6 years. In the survival group, mean age was 50.9 +/- 14.9 years; there were
      92 (62%) nondiabetics and 58 (38%) diabetics; the majority were nonvegetarians;
      148 patients were doing 6 - 8 L exchanges and 2 were doing >8 L exchanges daily;
      93 of 102 patients were average transporters based on peritoneal equilibration
      testing. At the beginning, mean combined Kt/V was 2.31 and weekly creatinine
      clearance was 73 L. Patients making one lifetime payment were 46% and 21%
      belonged to the full reimbursement group. RESULTS: Body mass index (BMI) was
      normal in 114 patients (76%). Ultrafiltration volume was 1377 +/- 452 at the
      start and 1400 +/- 461 mL/day after 3 years. Anuric patients at the start were
      12% and after 3 years 44%; urine output decreased from 527 +/- 26 to 253 +/- 14
      mL/day from the start to after 3 years. Peritonitis rate was 1 episode/75 patient
      months at the beginning and after 3 years it was 1 episode/30 patient-months.
      Exit-site care was done daily by 88% and 3 times weekly by 12%. Nonsmokers were
      92% and smokers were 8%. Those that lived in the city were 62% and rural areas
      were 38%. Mean blood pressure was 143 +/- 16/88 +/- 10 and 136 +/- 18/85 +/- 9
      mmHg, calcium x phosphorus product 44.6 +/- 15.6 and 45.9 +/- 15.7 mg(2)/dL(2),
      albumin 3.33 +/- 0.5 and 3.25 +/- 0.4 g/dL, hemoglobin 9.18 +/- 2 and 9.48 +/-
      1.8 g/dL at the beginning and after 3 years, respectively. Statistical analysis
      showed a significant fall in both systolic (p < or = 0.001) and diastolic blood
      pressure (p < or = 0.05), an increase in BMI (p < or = 0.01), and a decrease in
      blood urea (p < or = 0.001) in the survival group. Those with Hb > or = 11 g/dL
      survived longer (p < or= 0.001), those with serum albumin > or = 3 g/dL had
      better survival (p = 0.001), and anuric patients survived longer (p = 0.001).
      CONCLUSION: This multicenter cohort study of prevalent continuous PD patients in
      south India showed nondiabetics, average transporters, nonsmokers with reasonable
      nutritional status, with Hb 11 g/dL, with low peritonitis rate, with over 1 L
      ultrafiltration volume per day, the great majority that joined the once per
      lifetime payment scheme, and the reimbursement group survived for 3 years or
      longer.

PMID- 20056977
TI  - Glucose degradation products result in cardiovascular toxicity in a rat model of
      renal failure.
AB  - BACKGROUND: It has been shown that glucose degradation products (GDP) generated
      during heat sterilization of peritoneal dialysis (PD) fluids impair the
      peritoneal membrane locally, then enter the systemic circulation and cause damage
      to the remnant kidney. Here we examined in subtotally nephrectomized (SNX) rats
      whether GDP also affect the cardiovascular system. MATERIALS AND METHODS:
      Standard 5/6 nephrectomy was carried out in Sprague-Dawley rats; other rats were
      sham operated and left untreated for 3 weeks. Through an osmotic mini-pump,
      SNX+GDP group received GDP intravenously for 4 weeks; the SNX and the sham
      operated groups remained without GDP. The experiment was terminated for all
      groups 7 weeks postoperatively. We analyzed cardiovascular damage by serum
      analyses and immunohistochemical investigation. RESULTS: In SNX+GDP animals,
      expression of the advanced glycation end product (AGE) marker carboxymethyllysine
      and receptor of AGE (RAGE) were significantly higher in the myocardium and the
      aorta compared to the SNX rats. We also found significantly higher levels of
      apoptosis measured by caspase 3 staining in the cardiovascular system in the
      SNX+GDP group. Moreover, we observed a more pronounced expression of oxidative
      stress in the SNX+GDP rats compared to the SNX rats. In serum analyses, advanced
      oxidation protein products and reactive oxygen species were increased, as was
      immunohistochemical endothelial nitric oxide synthase. CONCLUSIONS: In addition
      to local toxic effects, GDP cause systemic toxicity. Here we showed that, in SNX
      rats, administration of GDP increased cardiovascular damage. In particular, we
      found increased levels of AGE, RAGE, oxidative stress, and apoptosis. Whether
      these findings are of clinical relevance has to be further investigated.

PMID- 20056978
TI  - The effects of previous abdominal operations and intraperitoneal adhesions on the
      outcome of peritoneal dialysis catheters.
AB  - BACKGROUND: Patients with previous history of abdominal operations are sometimes
      excluded from consideration for peritoneal dialysis because of concerns for
      increased risk of complications during the implantation procedure and inadequate
      dialysis due to reduced peritoneal surface area. Employing a laparoscopic
      approach, we compared the outcome of peritoneal dialysis catheters in 2 groups of
      patients with and without intra-abdominal adhesions. METHODS: All data in this
      report were recorded prospectively. Revision-free and overall survival of
      catheters, the incidence of mechanical and infectious complication, and surgical
      revision rates were compared between the 2 groups. RESULTS: In 217 successful
      catheter implantations, there was a history of previous abdominal surgery in
      42.9% of procedures; only 26.9% of them had intraperitoneal adhesions; 2.8% of
      patients without history of previous abdominal surgery had intraperitoneal
      adhesions. There were no significant differences between the 2 groups for 1- and
      2-year revision-free and overall catheter survival, mechanical dysfunction,
      infectious complications, or surgical revision rates. CONCLUSION: History of
      previous abdominal surgery should not be used to judge the eligibility of
      patients for peritoneal dialysis. Laparoscopic placement is the best way to
      ensure optimal catheter outcomes equivalent to patients without previous
      abdominal surgery.

PMID- 20056979
TI  - Comparative analysis of two-piece extended peritoneal dialysis catheters with
      remote exit-site locations and conventional abdominal catheters.
AB  - BACKGROUND: An alternative peritoneal catheter exit-site location is sometimes
      needed in patients with obesity, floppy skin folds, intestinal stomas, urinary
      and fecal incontinence, and chronic yeast intertrigo. Two-piece extended
      catheters permit remote exit-site locations away from problematic abdominal
      conditions. OBJECTIVE: The effect on clinical outcomes by remotely locating
      catheter exit sites to the upper abdomen or chest was compared to conventional
      lower abdominal sites. METHODS: In a nonrandomized design, peritoneal access was
      established with 158 extended catheters and 270 conventional catheters based upon
      body habitus and special clinical needs. Prospective data collection included
      patient demographics, infectious and mechanical complications, and catheter
      survival. RESULTS: Kaplan-Meier survival time until first exit-site infection was
      longer for extended catheters (p = 0.03). Poisson regression showed no difference
      in exit site, subcutaneous tunnel, and peritonitis infection rates; however, the
      proportion of catheters lost during peritonitis episodes was significantly
      greater for extended catheters (p = 0.007) and appeared to be due primarily to
      coagulase-negative staphylococcus organisms. Poisson regression showed
      interactions of body mass index (BMI) and diabetic status in determining catheter
      loss from peritonitis for both catheter types (p = 0.02). Extended catheter
      patients had higher BMI and diabetes prevalence (p < 0.0001). Overall extended
      catheter survival at 1, 2, and 3 years (92%, 80%, 71%) trended lower than
      conventional devices (93%, 87%, 80%; p = 0.0505). CONCLUSIONS: Extended catheters
      enable peritoneal access for patients in whom conventional catheter placement
      would be difficult or impossible. Certain patient and extended-catheter
      characteristics may contribute to loss from peritonitis.

PMID- 20056980
TI  - A prospective randomized study comparing tenckhoff catheters inserted using the
      triple incision method with standard swan neck catheters.
AB  - BACKGROUND AND OBJECTIVE: The downward directed exit of the swan neck catheter
      may decrease the risk of exit-site infection (ESI). The percentage of migrations
      of the swan neck catheter seems to be less than the conventional Tenckhoff
      catheter and the swan neck catheter is more expensive and cannot be manipulated
      by guidewire technique if tip migration occurs. In this study, the conventional
      Tenckhoff catheter was used. The straight tunnel was converted to an arcuate one
      using the triple incision method, resulting in a downward directed exit. The
      arcuate tunnel was created by passing the catheter through an additional incision
      located between the paramedian incision and the exit site. We compared the
      infective and mechanical complications of the Tenckhoff catheter with a downward
      exit, implanted using the triple incision method, with the swan neck catheter.
      PATIENTS AND METHODS: 101 new peritoneal dialysis patients were prospectively
      randomized to receive either the Tenckhoff catheter with a downward exit,
      implanted using the triple incision method, or the swan neck catheter. Each
      patient was followed up for 24 months. 50 patients were in the triple incision
      method group (TIMG) and 51 were in the swan neck catheter group (SNCG). RESULTS:
      Over a mean period of 18.9 +/- 8.0 months of follow-up, ESI occurred in 35
      patients (70%) in TIMG and 37 patients (72.5%) in SNCG (p = 0.83). The ESI rates
      were 0.71 and 1.0 episodes/catheter-year in TIMG and SNCG respectively (p =
      0.21). The peritonitis rates were similar in the 2 groups (0.64 episodes/year in
      TIMG and 0.68 episodes/year in SNCG, p = 0.47). More patients in TIMG had tip
      migration [15 patients (30%) in TIMG vs 10 patients (19.6%) in SNCG] but the
      difference was not statistically significant. Repositioning of the catheter by
      guidewire manipulation was successful in patients in TIMG but not in SNCG.
      Overall catheter survival at 12 and 24 months was 95% and 83% in TIMG and 93% and
      79% in SNCG respectively (p = 0.72). CONCLUSION: By using the conventional
      Tenckhoff catheter with a downward exit created using the triple incision method,
      high catheter survival rates with infective and mechanical complication rates
      similar to those of the swan neck catheter can be achieved. The triple incision
      method has the additional advantages of lower cost and the catheter can be
      manipulated by guidewire technique if tip migration occurs.

PMID- 20056981
TI  - Endoscopic transluminal insertion of a peritoneal dialysis catheter.
AB  - BACKGROUND: At present there are various more or less invasive surgical and
      laparoscopic ways to place a catheter suitable for peritoneal dialysis (PD);
      however, once the catheter is in place, there is no possibility to inspect the
      peritoneal cavity without de novo laparotomy or laparoscopy. PATIENTS AND
      METHODS: To establish a minimally invasive technique and allowing for maximal
      options, we used a PD catheter with an extra large inside diameter of 3.5 mm.
      Because of the enlarged inner diameter of 3.5 mm (compared to 2.6 mm in standard
      Tenckhoff catheters), this device can be passed by a very thin video-endoscope
      with an external diameter of 2.8 mm. Using a stepwise approach, we applied this
      device in placing PD catheters in 2 patients. The procedure could be done without
      complications. Both patients were doing well 4 and 6 months later, respectively,
      without any PD-related complications. Intraperitoneal view by the endoscope was
      limited; an attempt to obtain a peritoneal biopsy failed. CONCLUSIONS: If the
      drawbacks of this method can be overcome it will have a wide spectrum of
      applications (i.e., inspection of the peritoneal cavity and obtaining peritoneal
      biopsies at any time during PD treatment). In this way it can be used
      scientifically and clinically when a problem of flow or ultrafiltration occurs or
      when encapsulating sclerosing peritonitis is suspected.

PMID- 20056982
TI  - Angiotensin receptor blocker telmisartan improves insulin sensitivity in
      peritoneal dialysis patients.
AB  - BACKGROUND: Insulin resistance (IR) is common among patients on dialysis and is
      worse among patients on peritoneal dialysis (PD) than among patients on
      hemodialysis. In this study we tested the hypothesis that administration of
      telmisartan, an angiotensin II type 1 receptor antagonist, might improve insulin
      sensitivity in patients on PD. METHOD: This was a crossover study of 30
      nondiabetic patients with end-stage renal disease being treated with PD. Group A
      patients (n = 15) received telmisartan and other antihypertensive drugs for 4
      months, followed by 4 months without telmisartan. Group B patients (n = 15)
      received their usual treatment for 4 months, followed by 4 months of treatment
      with telmisartan. Blood glucose and serum insulin levels were monitored and
      homeostasis model assessment method for IR (HOMA-IR) was calculated. RESULTS:
      Treatment with telmisartan had no significant impact on serum glucose, potassium,
      and bicarbonate levels. However, telmisartan significantly reduced serum insulin
      levels and the HOMA index in groups A and B. CONCLUSION: This study demonstrated
      that telmisartan, an angiotensin receptor type 1 antagonist, may effectively
      improve insulin sensitivity as measured by HOMA in patients treated with PD.

PMID- 20056983
TI  - Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic
      subjects on peritoneal and hemodialysis.
AB  - BACKGROUND: Relative to hemoglobin A(1c) (HbA(1c)), percentage of glycated
      albumin (GA%) more accurately reflects recent glycemic control in diabetic
      hemodialysis (HD) patients. METHODS: To determine the accuracy of glycemic assays
      in a larger sample including patients on peritoneal dialysis (PD), HbA(1c) and
      GA% were measured in 519 diabetic subjects: 55 on PD, 415 on HD, and 49 non
      nephropathy controls. RESULTS: Mean +/- SD serum glucose levels were higher in HD
      and PD patients relative to non-nephropathy controls (HD 169.7 +/- 62 mg/dL, PD
      168.6 +/- 66 mg/dL, controls 146.1 +/- 66 mg/dL; p = 0.03 HD vs controls, p =
      0.13 PD vs controls). GA% was also higher in HD and PD patients (HD 20.6% +/-
      8.0%, PD 19.0% +/- 5.7%, controls 15.7% +/- 7.7%; p < 0.02 HD vs controls and PD
      vs controls). HbA(1c) was paradoxically lower in dialysis patients (HD 6.78% +/-
      1.6%, PD 6.87% +/- 1.4%, controls 7.3% +/- 1.4%; p = 0.03 HD vs controls, p =
      0.12 PD vs controls). The serum glucose/HbA(1c) ratio differed significantly
      between dialysis patients and controls (p < 0.0001 HD vs controls, p = 0.002 PD
      vs controls), while serum glucose/GA% ratio was similar across groups (p = 0.96
      HD vs controls, p = 0.64 PD vs controls). In best-fit multivariate models with
      HbA(1c) or GA% as outcome variable, dialysis status was a significant predictor
      of HbA(1c) but not GA%. CONCLUSIONS: The relationship between HbA(1c) and GA%
      differs in diabetic patients with end-stage renal disease who perform either PD
      or HD compared to those without nephropathy. HbA(1c) significantly underestimates
      glycemic control in peritoneal and hemodialysis patients relative to GA%.

PMID- 20056984
TI  - Arterial pulse wave velocity and peritoneal transport characteristics
      independently predict hospitalization in Chinese peritoneal dialysis patients.
AB  - OBJECTIVE: Cardiovascular disease (CVD) is the most common cause of mortality in
      chronic peritoneal dialysis (PD) patients. Increased arterial stiffness may be
      related to a high peritoneal permeability resulting in fluid overload in PD
      patients. We studied the relations between arterial stiffness, peritoneal
      transport, and radiographic parameters of systemic fluid overload in a cohort of
      Chinese PD patients. DESIGN: Prospective cohort study. SETTING: University
      referral center. PATIENTS: We studied 107 PD patients. Vascular pedicle width and
      cardiothoracic ratio were measured from a plain postero-anterior chest
      radiograph. Pulse wave velocity (PWV) was determined at carotid-femoral (C-F) and
      carotid-radial sites. Peritoneal transport was determined by the dialysate-to
      plasma ratio (D/P) of creatinine at 4 hours of dwell. Patients were followed for
      9.4 +/- 4.6 months. OUTCOME MEASURES: Duration of hospitalization; actuarial and
      technique survival. RESULTS: There were no relationships between radiographic
      measures, arterial PWV, and D/P creatinine. However, both C-F PWV and D/P
      creatinine were independent predictors of the number of hospitalizations for CVD.
      None of the parameters correlated with mortality in this study. CONCLUSIONS:
      There were no relationships between radiological parameters of fluid overload,
      peritoneal transport characteristics, and arterial PWV. Both C-F PWV and D/P
      creatinine were independent predictors of the number of hospitalizations for CVD.
      Our result suggests that arterial stiffness and high peritoneal transport each
      contribute to the development of CVD in this group of patients.

PMID- 20056985
TI  - Comparing survival between peritoneal dialysis and hemodialysis treatment in ESRD
      patients with chronic hepatitis C infection.
AB  - OBJECTIVE: End-stage renal disease (ESRD) patients with hepatitis C virus (HCV)
      infection are associated with an increasing mortality risk on hemodialysis (HD)
      and peritoneal dialysis (PD). The aim of this study was to compare patient
      survival between HCV-positive patients undergoing PD versus HD. METHODS: We
      reviewed 78 PD and 78 HD patients with chronic hepatitis C infection in China
      Medical University Hospital from 1996 to 2006. The HD patients were selected
      using the propensity score matching method. Kaplan-Meier analysis with log-rank
      test was used to compare patient survival between patients treated with PD and
      those treated with HD. Possible prognostic factors were analyzed using
      multivariate Cox proportional hazard regression with adjustments for age, sex,
      and propensity score. RESULTS: Mortality rate was 50% (39/78) for PD and 41%
      (32/78) for HD (chi-square test p = 0.26). Diabetes, hypertension, and
      cardiovascular disease were present in 43.6%, 25.6%, and 14.1% of patients,
      respectively. Kaplan-Meier estimate and univariate Cox regression with
      adjustments for age and propensity score showed that HCV patients treated with PD
      had a similar survival to those treated with HD (p = 0.381 and p = 0.363). In
      forward stepwise Cox regression, positivity for hepatitis B virus surface antigen
      (p < 0.001), diabetes (p = 0.009), and serum albumin (p = 0.032) were
      independently associated with higher mortality. CONCLUSION: Patient survival is
      not different between ESRD patients with chronic hepatitis C treated with PD and
      those treated with HD. In ESRD patients positive for HCV, being positive for
      hepatitis B virus is an important prognostic factor.

PMID- 20056986
TI  - Comparison of the multiple-aliquot and batch methods of monitoring peritoneal
      dialysis adequacy in patients.
AB  - BACKGROUND: Effluent fluid is analyzed to determine Kt/V urea and creatinine
      clearance as measures of adequacy of peritoneal dialysis. To avoid the physical
      mixing of fluids and to minimize handling of full effluent bags, a multiple
      aliquot method of sampling was developed and compared to the traditional batch
      method. METHODS: The batch method and the multiple-aliquot method were performed
      for 31 consecutive patients. Pooled fluid urea and creatinine measurements were
      determined for each method. PD Adequest 2.0 (Baxter Healthcare, Deerfield, IL,
      USA) was used to derive calculated peritoneal dialysis parameters. RESULTS: Urea
      dialysate levels, calculated weekly urea clearances, protein catabolic rate, and
      Kt/V were not statistically different (p > 0.05) between the 2 methods. Dialysate
      creatinine and creatinine clearance with the 2 methods were statistically
      distinct but the differences were not clinically important. The processing time
      per set of patient effluent bags was reduced from 45 to 18 minutes, handling of
      the bags was minimized, and error associated with inadequate mixing of pooled
      fluids was avoided. CONCLUSION: The multiple-aliquot method generates accurate
      and timely results to assess peritoneal dialysis prescription adequacy while
      reducing staff effort.

PMID- 20056987
TI  - Influence of the preceding dwell time on the peritoneal equilibration test with
      3.86% glucose solution in automated peritoneal dialysis.
AB  - OBJECTIVE: The peritoneal equilibration test (PET) using 3.86% glucose solution
      is preceded by a long dwell with 3.86% glucose solution. A point of concern in
      patients treated with automated peritoneal dialysis (APD) is the influence of the
      preceding short nightly dwells on the results of a standardized PET. The aim of
      the study was to compare net ultrafiltration, small solute transport, sodium
      sieving, and solute transport type between a PET preceded by a long night dwell
      and one preceded by short (APD) dwells. PATIENTS AND METHODS: 13 stable APD
      patients (mean age 60 +/- 15 years; mean duration of peritoneal dialysis 31 +/-
      15 months) underwent 2 PETs: 1 preceded by short nightly dwells (PET A) and 1
      preceded by a long night dwell (PET B). RESULTS: Both PETs were performed within
      a mean period of 8 (range 5 - 11) days. Mean total ultrafiltration of PET A was
      626 +/- 218 mL and PET B was 644 +/- 223 mL (NS). The 4-hour results of both
      tests for dialysate-to-plasma (D/P) ratios of creatinine and urea, D(t)/D(0)
      ratios of glucose, and the dip in D/P sodium (sodium sieving) were similar.
      Classification of transport categories was identical for 10 of 13 patients.
      CONCLUSION: In APD, the preceding dwell time of a 3.86% glucose PET does not
      influence fluid transport, solute transport, or transport type.

PMID- 20056988
TI  - Campylobacter peritonitis complicating continuous ambulatory peritoneal dialysis:
      report of three cases and review of the literature.
AB  - BACKGROUND: The micro-organisms involved in continuous ambulatory peritoneal
      dialysis (CAPD) peritonitis are usually gram-positive cocci of cutaneous origin.
      Campylobacter species are rarely implicated as a cause of CAPD peritonitis.
      METHODS: A retrospective review of 100 consecutive episodes of peritonitis was
      carried out in patients undergoing CAPD or automated PD in our hospital from June
      2004 to December 2007. Collection of dialysate and microbial examination was done
      according to ISPD guidelines. Identification of the organism was made on the
      basis of Gram smear morphology, positive oxidase test, and biochemical reactions
      using API Campi (BioMerieux, Marcy l'Etoile, France). Susceptibility testing was
      performed using E-test (AB Biodisc, Solna, Sweden) and confirmation was done by
      molecular techniques. RESULTS: The causative organisms in 23 of these episodes
      were gram-negative bacteria, 3 of which were identified as Campylobacter species
      using special culture techniques. The clinical presentation in our patients with
      Campylobacter peritonitis (CP) was different from that of patients with
      peritonitis from other organisms in that all 3 had diarrhea at presentation.
      Among patients with CP, no subspecies-specific feature was identified. Good
      response to the antibiotic treatment was observed; there was no
      relapse/recurrence of peritonitis, catheter loss, or death. CONCLUSION: Incidence
      of CP remains low and, regardless of the subtype, clinical outcomes are better
      than those seen with other gram-negative bacteria such as Pseudomonas. The
      presence of diarrhea at presentation and the finding of curved or spiral gram
      negative bacilli in the Gram smear of peritoneal dialysis effluent should make
      one think of CP. The use of appropriate microbiology techniques in this situation
      will increase the isolation of this organism.

PMID- 20056989
TI  - Stability of N-acetylcysteine in peritoneal dialysis solution.

PMID- 20056990
TI  - Encapsulating peritoneal sclerosis in a patient with primary hyperoxaluria type
      1: a case report.
AB  - Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder caused by a
      defect in glyoxylate metabolism attributable to low or absent activity of the
      liver-specific peroxisomal enzyme alanine/glyoxylate aminotransferase. This
      defect leads to enhanced conversion of glyoxylate to poorly soluble oxalate,
      which is then excreted into the urine. This process may lead to deposition of
      calcium oxalate crystals in many tissues as well as in the kidneys, resulting in
      nephrolithiasis, nephrocalcinosis, and/or renal failure. We present a 39-year-old
      patient with end-stage renal failure due to PH1, who was admitted with symptoms
      of feeling bloated, vomiting, diarrhea, and abdominal pain related to
      encapsulating peritoneal sclerosis (EPS). He had been treated with peritoneal
      dialysis for a total period of 5 years. EPS is a rare condition characterized by
      fibrosis and adhesions of the peritoneum to loops of the small intestine and has
      been described secondary to treatment with peritoneal dialysis. It also occurs in
      a variety of other clinical conditions such as autoimmune diseases and peritoneal
      and intra-abdominal malignancies. The calcium oxalate crystals found in the
      peritoneal fascia of this particular patient may suggest a causative relationship
      between crystal deposits and evolution to fibrosis and sclerosis of the
      peritoneum. The degree of impact of the peritoneal dialysis treatment itself on
      the development of EPS, however, is uncertain.

PMID- 20056991
TI  - Peritoneal scintigraphy in the diagnosis of adhesions.

PMID- 20056992
TI  - The use of biocompatible solutions does not prevent development of encapsulating
      peritoneal sclerosis.

PMID- 20056993
TI  - Successful peritoneal dialysis in a hemophilia A patient with factor VIII
      inhibitor.
AB  - Chronic kidney disease and need for renal replacement therapy in hemophiliacs are
      relatively rare occurrences. Successful hemodialysis and peritoneal dialysis
      applications have been reported in the literature. We report a difficult-to
      manage patient with hemophilia A plus factor VIII inhibitor who presented with
      gastrointestinal bleeding complicated by uremia. We admitted this hemophilia A
      patient with gastrointestinal bleeding who did not take regular factor infusions.
      He also had chronic kidney disease due to urinary stone disease. Since uremia
      might have contributed to bleeding, we chose hemodialysis along with factor VIII
      supplementation. His factor VIII and factor VIII inhibitor levels were 4% and 5
      Bethesda units respectively. In order to bypass the inhibitor, we applied factor
      VIIA and prothrombin complex concentrate. After cessation of the hemorrhage, we
      placed a Tenckhoff catheter under prothrombin complex concentrate infusion. We
      did not observe any perioperative complication. To our knowledge, this is the
      first report of successful peritoneal dialysis in a hemophilia A patient who had
      factor VIII inhibitors.

PMID- 20056994
TI  - Peritoneal dialysis-related peritonitis due to Neisseria weaveri: the first case
      report.

PMID- 20056995
TI  - Peritonitis due to teicoplanin-resistant Staphylococcus haemolyticus.

PMID- 20056996
TI  - First reported case of Alcaligenes faecalis peritonitis.

PMID- 20056997
TI  - First case of CAPD-related peritonitis caused by Morganella morganii.
AB  - Morganella morganii, a gram-negative bacillus, is a rare cause of peritonitis. In
      this article we report a 55-year-old female patient with peritonitis due to
      Morganella morganii who was receiving continuous ambulatory peritoneal dialysis
      (CAPD).

PMID- 20056999
TI  - Psychosis due to non-bacterial thrombotic endocarditis.
AB  - Non-bacterial thrombotic endocarditis or marantic endocarditis is an uncommon and
      frequently terminal condition. We report non-bacterial thrombotic endocarditis
      presenting as a psychotic illness. The underlying cause was found to be
      adenocarcinoma of the lung. The patient was nursed on a specialist joint
      medical/psychiatric unit. Many medical illnesses can present with psychosis in
      older people: this is the first case report of this presentation in non-bacterial
      thrombotic endocarditis.

PMID- 20056998
TI  - Novel thioredoxin-related transmembrane protein TMX4 has reductase activity.
AB  - In the endoplasmic reticulum (ER), a number of thioredoxin (Trx) superfamily
      proteins are present to enable correct disulfide bond formation of secretory and
      membrane proteins via Trx-like domains. Here, we identified a novel transmembrane
      Trx-like protein 4 (TMX4), in the ER of mammalian cells. TMX4, a type I
      transmembrane protein, was localized to the ER and possessed a Trx-like domain
      that faced the ER lumen. A maleimide alkylation assay showed that a catalytic
      CXXC motif in the TMX4 Trx-like domain underwent changes in its redox state
      depending on cellular redox conditions, and, in the normal state, most of the
      endogenous TMX4 existed in the oxidized form. Using a purified recombinant
      protein containing the Trx-like domain of TMX4 (TMX4-Trx), we confirmed that this
      domain had reductase activity in vitro. The redox potential of this domain (
      171.5 mV; 30 degrees C at pH 7.0) indicated that TMX4 could work as a reductase
      in the environment of the ER. TMX4 had no effect on the acceleration of ER
      associated degradation. Because TMX4 interacted with calnexin and ERp57 by co
      immunoprecipitation assay, the role of TMX4 may be to enable protein folding in
      cooperation with these proteins consisting of folding complex in the ER.

PMID- 20057000
TI  - [Dreams and imaginations in the therapy of eating disordered patients.]
AB  - Recently the integrative approach has been applied in the treatment of eating
      disorders with multicausal origin. In order to achieve long-term therapeutic
      effect, the psychodynamic interpretation is often needed and favoured as a part
      of the personal, multimodal therapeutic strategy. The present paper focuses on
      body image distortion as one of the most decisive and least influenceable symptom
      of the disorder. The symptom is interpreted along the body image distortion-body
      boundaries-self boundaries-autonomy line. With illustrative therapy details of
      dreams, imaginations, the authors aim to demonstrate the therapeutic use of
      dynamically oriented therapy and dynamically oriented hypnotherapy.

PMID- 20057001
TI  - [Game rules Representing the characteristics of regulation in child and
      adolescent anorexia nervosa with World-Playing Test.]
AB  - One of the most crucial problems concerning the pathogenesis of anorexia nervosa
      is the deficit of regulation. This problem appears in the symptoms, in the
      cognitive infexibility, in the levels of self organizations, in mother- child and
      familial relationships. The present paper tries to search for paralells
      addressing deficits of regulation by overviewing the theories of anorexia
      nervosa. Moreover, the World-Playing Test is presented as a projective method for
      the detection of these deficits. The test was used in 50 adolescent anorexia
      nervosa cases in the last years. The idiosyncratic traits of psychopathology are
      noticeable in the characteristics of buildups. The deficits of regulation
      appeared in signs as perceptual rigidity, perfectionism, compulsions,
      overwhelming and unregulated emotions, and in connection with these traits, the
      need of permanent control. The World-Playing Test proved to be an effective and
      rich psychodiagnostic method, which helps us not only to verify general
      theoretical conclusions, but also to understand the individual psychodynamic
      organization.

PMID- 20057002
TI  - [Body symbolics of anorectic women.]
AB  - Aim: Body image and its disorder is an important issue in anorexia nervosa. The
      aim of the present paper is to approach this issue by a symbol test and to
      demonstrate the image what anorectic women create about their own body through
      several symbols. Method: 29, 13-35 year old anorectic and 29 15-35 year old
      healthy women were tested with Jacqueline Royer's Metamorphosis Test. The test is
      based on the Jungian and Bourdonian psychology, and examines the dynamic,
      altering part of the personality through the motivation and identification
      system. Results: Among anorectic women - opposed to healthy women - similar
      answers, symbols appeared, which differ from the vulger answers of the test, and
      show a plain or deep analogy with the physical and psychical symptoms of anorexia
      nervosa. 15,7% of the answers given to the Figure question by anorectic women
      have a symbolic reference to "deformed" quality. In the category of Material,
      6,2% of their answers show the symbolics of "fire" and "burning". 21,0% of their
      answers given to the category of Landscape symbolise "withering" and "dying"
      parts of nature. Conclusions: The imaginative expression of the similar symbols
      given by anorectic women help us to conceive the psychodynamical background and
      the subjective somatic-psychical meaning of the disease in a more complex way.

PMID- 20057003
TI  - [Cognitive behavior therapy in eating disorders.]
AB  - Author's aim is to give a comprehensive review of the behavioural and cognitive
      behavioural psychotherapeutic development in the treatment of anorexia nervosa
      and bulimia nervosa, on the base of the literature as well as on own clinical
      experiences. Behavioural therapies, currently applied as part of integrative
      therapies mainly, will be shown, and theoretical background and techniques of
      classical cognitive behavioural therapy of anorexia and bulimia nervosa will be
      shortly summarized. Theory and therapeutic techniques of the schema-focused
      cognitive behavioural therapy, applied in the treatment of eating disorders more
      frequently in the last few years, will be made acquainted in details. Indications
      and contraindications of classic cognitive behavioural therapy and schema-focused
      cognitive behavioural therapy in eating disorders will be discussed. Stress will
      be laid on the fact, that schema-focused cognitive behaviour therapy is to be
      chosen mostly in the cases where comorbid dissociation, personality disorder,
      very low self-esteem or traumatic history diminishes the applicability of
      traditional cognitive behavioural therapy. Authors emphasize the importance of
      further controlled efficacy studies in the field of schema-focused cognitive
      behavioural therapy, to define the indication fields regarding different
      subgroups of eating disorders.

PMID- 20057004
TI  - [Binge eating, overweight, obesity. Psychotherapeutical approach of obesity.]
AB  - Obesity is a global epidemic with serious health consequences. Behavior therapy
      is one of the evidence based methods in the treatment of obesity. According to
      several studies these programs induce modest (cca. 10 %) weight reduction that is
      associated with statistically and clinically substantial improvements in weight
      related health conditions and psychosocial outcomes. Reduced weight is usually
      maintained for a relatively long time, cca. 2-3 years. Cognitive and affective
      processes seem to play an important role in weight regain. This led to the
      development of cognitive behavioral treatment approaches. This paper describes
      the behavior therapy and cognitive-behavioral treatment of obesity.

PMID- 20057005
TI  - 2D D-bar reconstructions of human chest and tank data using an improved
      approximation to the scattering transform.
AB  - The D-bar method for electrical impedance tomography requires the computation of
      an intermediate function known as the scattering transform from the measured
      data. An approximation to the scattering transform utilizing the standard Green's
      function for the Laplacian was introduced for the 2D D-bar method in Mueller and
      Siltanen (2003 SIAM J. Sci. Comp. 24 1232-66) and tested on simple numerically
      simulated conductivity distributions. In this work, the approximation is
      implemented for experimental data for the first time. It is tested on both tank
      and human chest data, and the results demonstrate decreased blurring toward the
      boundary in the images than in images computed with the t(exp) approximation to
      the scattering transform.

PMID- 20057006
TI  - Modeling the role of covalent enzyme modification in Escherichia coli nitrogen
      metabolism.
AB  - In the bacterium Escherichia coli, the enzyme glutamine synthetase (GS) converts
      ammonium into the amino acid glutamine. GS is principally active when the cell is
      experiencing nitrogen limitation, and its activity is regulated by a bicyclic
      covalent modification cascade. The advantages of this bicyclic-cascade
      architecture are poorly understood. We analyze a simple model of the GS cascade
      in comparison to other regulatory schemes and conclude that the bicyclic cascade
      is suboptimal for maintaining metabolic homeostasis of the free glutamine pool.
      Instead, we argue that the lag inherent in the covalent modification of GS slows
      the response to an ammonium shock and thereby allows GS to transiently detoxify
      the cell, while maintaining homeostasis over longer times.

PMID- 20057007
TI  - An accelerated ordered subsets reconstruction algorithm using an accelerating
      power factor for emission tomography.
AB  - We proposed a speed-enhanced tomographic reconstruction algorithm, ACOSEM
      (accelerated complete-data ordered-subset expectation-maximization), to
      accelerate a convergent OS-type algorithm (COSEM). The ACOSEM algorithm was based
      on modification of the COSEM update by applying an accelerating power factor or a
      bigger step size. Unlike the limited enhancement of the other speed-enhanced
      algorithm (E-COSEM), the proposed ACOSEM with an appropriate power factor can
      lead to a much faster reconstruction speed than COSEM and ECOSEM. Similar to
      COSEM, there is no free user-entered relaxation parameter needed for ACOSEM to
      ensure the convergent performance as required in the other type of fast
      convergent algorithms such as RAMLA. We derived the ACOSEM algorithm, and
      compared its performance to those of other fast convergent algorithms including
      COSEM, ECOSEM and RAMLA with optimized relaxation parameters. Though not
      convergent, OSEM is the current state-of-the-art reconstruction method used in
      the clinics, and thus included in the noise performance comparison. The results
      showed that ACOSEM reached the same image quality as in COSEM but two times
      faster when a power factor of 2.0 was used. An upper limit of 5 for the power
      factor with monotonically increasing log-likelihood in ACOSEM was observed under
      various conditions. Although the convergence proof is not available now, the
      results of log-likelihood values and noise studies showed that ACOSEM performed
      consistently with COSEM but with an accelerating reconstruction speed.

PMID- 20057008
TI  - Validation of a new grid-based Boltzmann equation solver for dose calculation in
      radiotherapy with photon beams.
AB  - A new grid-based Boltzmann equation solver, Acuros, was developed specifically
      for performing accurate and rapid radiotherapy dose calculations. In this study
      we benchmarked its performance against Monte Carlo for 6 and 18 MV photon beams
      in heterogeneous media. Acuros solves the coupled Boltzmann transport equations
      for neutral and charged particles on a locally adaptive Cartesian grid. The
      Acuros solver is an optimized rewrite of the general purpose Attila software, and
      for comparable accuracy levels, it is roughly an order of magnitude faster than
      Attila. Comparisons were made between Monte Carlo (EGSnrc) and Acuros for 6 and
      18 MV photon beams impinging on a slab phantom comprising tissue, bone and lung
      materials. To provide an accurate reference solution, Monte Carlo simulations
      were run to a tight statistical uncertainty (sigma approximately 0.1%) and fine
      resolution (1-2 mm). Acuros results were output on a 2 mm cubic voxel grid
      encompassing the entire phantom. Comparisons were also made for a breast
      treatment plan on an anthropomorphic phantom. For the slab phantom in regions
      where the dose exceeded 10% of the maximum dose, agreement between Acuros and
      Monte Carlo was within 2% of the local dose or 1 mm distance to agreement. For
      the breast case, agreement was within 2% of local dose or 2 mm distance to
      agreement in 99.9% of voxels where the dose exceeded 10% of the prescription
      dose. Elsewhere, in low dose regions, agreement for all cases was within 1% of
      the maximum dose. Since all Acuros calculations required less than 5 min on a
      dual-core two-processor workstation, it is efficient enough for routine clinical
      use. Additionally, since Acuros calculation times are only weakly dependent on
      the number of beams, Acuros may ideally be suited to arc therapies, where current
      clinical algorithms may incur long calculation times.

PMID- 20057009
TI  - Reducing the number of segments in unidirectional MLC segmentations.
AB  - In intensity-modulated radiation therapy (IMRT), fluence matrices obtained from a
      treatment planning system are usually delivered by a linear accelerator equipped
      with a multileaf collimator (MLC). A segmentation method is needed for
      decomposing these fluence matrices into segments suitable for the MLC, and the
      number of segments used is an important factor for treatment time. In this work,
      an algorithm for reduction of the number of segments (NS) is presented for
      unidirectional segmentations, where there is no backtracking of the MLC leaves.
      It uses a geometrical representation of the segmentation output for searching the
      key values in a fluence matrix that complicate its decomposition. The NS
      reduction is achieved by performing minor modifications in these values, under
      the conditions of avoiding substantial modifications of the dose-volume
      histogram, and does not increase in average the total number of monitor units
      delivered. The proposed method was tested using two clinical cases planned with
      the PCRT 3D treatment planning system.

PMID- 20057011
TI  - A sector-integration method for dose/MU calculation in a uniform scanning proton
      beam.
AB  - An accurate, simple and time-saving sector integration method for calculating the
      proton output (dose/monitor unit, MU) is presented based on the following
      treatment field parameters: aperture shape, aperture size, measuring position,
      beam range and beam modulation. The model is validated with dose/MU values for
      431 fields previously measured at our center. The measurements were obtained in a
      uniform scanning proton beam with a parallel plate ionization chamber in a water
      phantom. For beam penetration depths of clinical interest (6-27 cm water),
      dose/MU values were measured as a function of spread-out Bragg peak (SOBP) extent
      and aperture diameter. First, 90 randomly selected fields were used to derive the
      model parameters, which were used to compute the dose/MU values for the remaining
      341 fields. The min, max, average and the standard deviation of the difference
      between the calculated and the measured dose/MU values of the 341 fields were
      used to evaluate the accuracy and stability, for different energy ranges,
      aperture sizes, measurement positions and SOBP values. The experimental results
      of the five different functional sets showed that the calculation model is
      accurate with calculation errors ranging from -2.4% to 3.3%, and 99% of the
      errors are less than +/-2%. The accuracy increases with higher energy, larger
      SOBP and bigger aperture size. The average error in the dose/MU calculation for
      small fields (field size <25 cm(2)) is 0.31 +/- 0.96 (%).

PMID- 20057012
TI  - Effective dose analysis of three-dimensional rotational angiography during
      catheter ablation procedures.
AB  - There is increasing use of three-dimensional rotational angiography (3DRA) during
      cardiac ablation procedures. As compared with 2D angiography, a large series of
      images are acquired, creating the potential for high radiation doses. The aim of
      the present study was to quantify patient-specific effective doses. In this
      study, we developed a computer model to accurately calculate organ doses and the
      effective dose incurred during 3DRA image acquisition. The computer model
      simulates the exposure geometry and uses the actual exposure parameters,
      including the variation in tube voltage and current that is realized through the
      automatic exposure control (AEC). We performed 3DRA dose calculations in 42
      patients referred for ablation on the Siemens Axiom Artis DynaCT system
      (Erlangen, Germany). Organ doses and effective dose were calculated separately
      for all projections in the course of the C-arm rotation. The influence of patient
      body mass index (BMI), dose-area product (DAP), collimation and dose per frame
      (DPF) rate setting on the calculated doses was also analysed. The effective dose
      was found to be 5.5 +/- 1.4 mSv according to ICRP 60 and 6.6 +/- 1.8 mSv
      according to ICRP 103. Effective dose showed an inversely proportional
      relationship to BMI, while DAP was nearly BMI independent. No simple conversion
      coefficient between DAP and effective dose could be derived. DPF reduction did
      not result in a proportional effective dose decrease. These paradoxical findings
      were explained by the settings of the AEC and the limitations of the x-ray tube.
      Collimation reduced the effective dose by more than 20%. Three-dimensional
      rotational angiography is associated with a definite but acceptable radiation
      dose that can be calculated for all patients separately. Their BMI is a predictor
      of the effective dose. The dose reduction achieved with collimation suggests that
      its use is imperative during the 3DRA procedure.

PMID- 20057013
TI  - Comments on 'The influence of a novel transmission detector on 6 MV x-ray beam
      characteristics'.
AB  - In their recent paper (Venkataraman et al 2009 Phys. Med. Biol. 54 3173-83) the
      authors reported on photon beam attenuation and secondary electron production in
      the novel transmission detector COMPASS, to be placed in the accessory holder of
      the linac treatment head. In the interest of IMRT patient safety, space-resolved
      measurements by transmission detectors analysing the MLC-shaped photon fluence
      pattern in real time are in fact an urgent item for equipment designers. However,
      there are some constraints for the construction of such devices. The COMPASS
      system, at its present stage of development, has difficulties in complying with
      the constraints that the spatial sampling rate should fit the desired task and
      that the enhanced secondary electron contamination of the photon beam due to the
      presence of the device should be minimized. The authors also missed to mention a
      forerunner in this field, the DAVID transmission detector (Poppe et al 2006 Phys.
      Med. Biol. 51 1237-48), serving for the real-time supervision of the MLC aperture
      during patient treatment and ever since proven in clinical practice. The DAVID
      system, a transparent multiwire ionization chamber placed in the accessory
      holder, will be shortly described.

PMID- 20057014
TI  - Conversion of borate-based glass scaffold to hydroxyapatite in a dilute phosphate
      solution.
AB  - Porous scaffolds of a borate-based glass (composition in mol%: 6Na2O, 8K2O, 8MgO,
      22CaO, 36B2O3, 18SiO2, 2P2O5), with interconnected porosity of approximately 70%
      and pores of size 200-500 microm, were prepared by a polymer foam replication
      technique. The degradation of the scaffolds and conversion to a hydroxyapatite
      type material in a 0.02 M K2HPO4 solution (starting pH = 7.0) at 37 degrees C
      were studied by measuring the weight loss of the scaffolds, as well as the pH and
      the boron concentration of the solution. X-ray diffraction, scanning electronic
      microscopy and energy dispersive x-ray analysis showed that a hydroxyapatite-type
      material was formed on the glass surface within 7 days of immersion in the
      phosphate solution. Cellular response to the scaffolds was assessed using murine
      MLO-A5 cells, an osteogenic cell line. Scanning electron microscopy showed that
      the scaffolds supported cell attachment and proliferation during the 6 day
      incubation. The results indicate that this borate-based glass could provide a
      promising degradable scaffold material for bone tissue engineering applications.

PMID- 20057015
TI  - An in vitro multi-parametric approach to measuring the effect of implant surface
      characteristics on cell behaviour.
AB  - Orthopaedic implants are designed to promote biocompatibility and hence their
      integration with surrounding tissue. This involves influencing cell-implant
      interactions through changes in both surface topography and surface roughness.
      However, the large range of machining techniques used in implant manufacture and
      inconsistencies in the measurement techniques used for surface characterization
      make it difficult to measure the impact of surface characteristics on cell
      implant interactions. Here, we describe a new in vitro multi-parametric approach
      that uses commercially available arrays of engineered surfaces that linearly
      increase in roughness, as measured by Ra, and that can be used to obtain
      quantitative measurements of cell attachment, differentiation and bone formation.
      Using this model, we demonstrate that cell attachment above 50% confluency occurs
      over a narrow range of roughness (Ra from 0.0125 microm to 6.3 microm) and that
      promotion of cell differentiation and bone development, while significantly
      influenced by surface topography, does not correlate directly with initial levels
      of cell attachment. These results compare well with published in vivo implant
      biocompatibility data indicating that this approach has the potential to offer a
      rapid, reliable and reproducible in vitro prediction of in vivo implant
      biocompatibility.

PMID- 20057016
TI  - Phase transformation behaviour of hydroxyapatite foams subject to heat treatment.
AB  - This study examined the relationship between sintering and phase transformation
      behaviour in hydroxyapatite (HA). Pellets and replicated foams were sintered at
      five different temperatures ranging from 1350 degrees C to 1550 degrees C.
      Hydroxyapatite remained as the major phase in all the samples studied. In the
      pellets, sintering took place prior to the phase transformation which occurs
      primarily at the surface. This created damage that extended into the interior of
      the pellet above 1400 degrees C. In contrast, the foams transformed at lower
      temperatures due to the higher surface area. This did not create damage in the
      foam. The differences in the foams and the pellets are discussed in terms of
      sintering and phase transformation behaviour.

PMID- 20057017
TI  - A novel calcium phosphate ceramic-magnetic nanoparticle composite as a potential
      bone substitute.
AB  - A magnetic field has been applied to accelerate bone healing for a long time. In
      this study, in order to combine the bone repair capability of calcium phosphate
      (CaP) ceramics with the magnetic field, a novel CaP ceramic-magnetic nanoparticle
      (CaP-MNP) composite was fabricated through integrating the superparamagnetic
      nanoparticles into the CaP ceramics. Two kinds of CaP ceramics were chosen:
      hydroxyapatite (HA) and HA/tricalcium phosphate (65/35, HT). The samples were
      cultured with Ros17/2.8 and MG63 cells respectively in vitro to evaluate the cell
      proliferation and differentiation via MTT and alkaline phosphatase activity
      tests. In order to find the influence of the magnetic materials on the expression
      of the bone morphological protein (BMP), the samples composited with BMP-2 were
      implanted subcutaneously in the fasciae of rat back muscles for 30 days. Compared
      with ordinary CaP ceramics, the results indicated that the CaP-MNP composite had
      good biocompatibility and was able to promote cell proliferation and
      differentiation significantly. The in vivo test showed that the expression of BMP
      2 would be accelerated by HT composited with MNPs, and new bone-like tissue
      formation could be observed. Accordingly, it might be expected that this CaP-MNP
      composite could become a potential bone substitute or bone tissue engineering
      scaffold.

PMID- 20057018
TI  - Impact of trace elements on biocompatibility of titanium scaffolds.
AB  - A titanium oxide scaffold has recently been reported with high compressive
      strength (>2 MPa) which may allow its use in bone. However, would it be possible
      to enhance the scaffolds' performance by selecting a titanium oxide raw material
      without elemental contamination? Elements in implant surfaces have been reported
      to provoke implant failure. Thus, this study aims to compare different commercial
      titanium dioxide powders in order to choose the appropriate powder for scaffold
      making. The x-ray photoelectron spectroscopy (XPS) analysis identified the trace
      elements, mainly Al, Si, C, Ca and P. Cellular response was measured by cytotoxic
      effect, cell growth and cytokine secretion from murine preosteoblasts (MC3T3-E1)
      in vitro. The XPS data showed that traces of carbon-based molecules, silicon,
      nitrogen and aluminium in the powder were greatly reduced after cleaning in 1 M
      NaOH. As a result, reduction in cytotoxicity and inflammatory response was
      observed. Carbon contamination seemed to have a minor effect on the cellular
      response. Strong correlations were found between Al and Si contamination levels
      and the inflammatory response and cytotoxic effect. Thus, it is suggested that
      the concentration of these elements should be reduced in order to enhance the
      scaffolds' biocompatibility.

PMID- 20057019
TI  - Improvement of dehydrogenation kinetics of LiBH(4) dispersed on modified multi
      walled carbon nanotubes.
AB  - The dehydrogenation kinetics of LiBH(4) dispersed on multi-walled carbon
      nanotubes (MWCNTs) by the solvent infiltration technique has been studied.
      Commercial MWCNTs were ball-milled for different milling times in order to
      increase the specific surface area (SSA) as measured by the BET technique.
      Thermal programmed desorption measurements have been performed using a Sievert's
      apparatus on samples with different SSA of MWCNTs and different LiBH(4) to MWCNT
      ratio. Pressure composition isotherms (PCI) have been obtained at different
      temperatures in order to estimate the DeltaH and DeltaS of dehydrogenation. It
      has been observed that the dispersion of LiBH(4) on MWCNTs leads to a lower
      dehydrogenation temperature compared to pure LiBH(4). Moreover, the
      dehydrogenation temperature further decreases with increasing MWCNT surface area.
      An interpretation of the kinetic effect is proposed.

PMID- 20057020
TI  - Soft-contact imaging in liquid with frequency-modulation torsion resonance mode
      atomic force microscopy.
AB  - In this work, we demonstrate that high-resolution imaging in water with a soft
      contact between the tip and the sample can be achieved with frequency-modulation
      torsional resonance (FM-TR) mode atomic force microscopy (AFM). This mode is very
      sensitive to the contact of the tip with the sample surface. A sharp jump in the
      resonance frequency shift occurs when the tip is getting in touch with the
      sample. Individual atomic features on mica surfaces can be resolved with a
      relatively large tip. The tip applies very small normal and lateral forces on the
      surface. In addition, even a long and compliant AFM cantilever can achieve a high
      quality factor and a high resonant frequency for the torsional oscillation in
      water. Along with several other advantages, this mode is very suitable for future
      development of high-sensitivity, high-resolution, high-speed AFM for the study of
      dynamic biological processes in liquid.

PMID- 20057021
TI  - Water motion and movement without sticking, weight loss and cross-contaminant in
      superhydrophobic glass tube.
AB  - We report that a simple fabrication of a superhydrophobic nanosurface consisted
      of a grass-like silica thin film on the inner wall of a glass tube and its
      feature in water motion and water movement. The glass tube with a
      superhydrophobic inner wall can make the water flow with friction-drag reduction
      and completely preventing water sticking. Transferring water by this tube did not
      cause weight loss at all. Therefore, aqueous solutions containing high content
      metal ions were cross-moved without washing the tube used and no cross
      contamination occurred after cross-movement. Furthermore, in an inside diameter
      of 6.0 mm glass tube where the half-length of the inner surface is covered by
      superhydrophobic nanograss and the other half is an unmodified hydrophilic
      surface, the water droplets flowing down from the hydrophilic side can be stopped
      spontaneously at the hydrophilic-superhydrophobic boundary as if there is an
      invisible flow-stopping fence built inside the glass tube.

PMID- 20057022
TI  - Generic nano-imprint process for fabrication of nanowire arrays.
AB  - A generic process has been developed to grow nearly defect-free arrays of
      (heterostructured) InP and GaP nanowires. Soft nano-imprint lithography has been
      used to pattern gold particle arrays on full 2 inch substrates. After lift-off
      organic residues remain on the surface, which induce the growth of additional
      undesired nanowires. We show that cleaning of the samples before growth with
      piranha solution in combination with a thermal anneal at 550 degrees C for InP
      and 700 degrees C for GaP results in uniform nanowire arrays with 1% variation in
      nanowire length, and without undesired extra nanowires. Our chemical cleaning
      procedure is applicable to other lithographic techniques such as e-beam
      lithography, and therefore represents a generic process.

PMID- 20057023
TI  - Stable enhancement of near-band-edge emission of ZnO nanowires by hydrogen
      incorporation.
AB  - We report on the photoluminescence properties of ZnO nanowires treated with a
      mild Ar plasma. The nanowires exhibited stable and strong enhancement of the near
      band-edge emission and quenching of the deep level emission. The low temperature
      PL revealed a strong hydrogen donor-bound-exciton line in the plasma-treated
      samples indicating unintentional incorporation of hydrogen during the plasma
      treatment. To confirm the results, hydrogen was implanted into the ZnO nanowires
      with a low ion energy of 600 eV and different fluences. The observed result can
      be related to the passivation of deep centers by hydrogen. The absolute
      photoluminescence intensity measured by an integrating sphere showed stable and
      strong UV emission from the treated samples even after several weeks.

PMID- 20057024
TI  - Delivery of paclitaxel by physically loading onto poly(ethylene glycol) (PEG)
      graft-carbon nanotubes for potent cancer therapeutics.
AB  - Physically loading of paclitaxel (PTX) onto carbon nanotubes (CNTs) is achieved
      through immersion of poly(ethylene glycol) (PEG)-graft-single walled CNTs (PEG-g
      SWNTs) or PEG-graft-multi-walled CNTs (PEG-g-MWNTs) in a saturated solution of
      PTX in methanol. After loading once the loading capacity (LD%) is 26% (w/w) and
      36% (w/w) for PEG-g-SWNTs or PEG-g-MWNTs, respectively. With these PTX contents,
      PTX loaded PEG-g-SWNTs and PTX loaded PEG-g-MWNTs still have good dispersity in
      aqueous solution and individual CNTs can be observed in TEM images. PTX can be
      released from PEG-g-CNTs several times faster than from free PTX but still in a
      sustained profile with less than 40% of PTX being released in 40 days at pH 7 or
      5. In vitro cytotoxicity of samples is evaluated in HeLa cells and MCF-7 cells.
      PEG-g-SWNTs and PEG-g-MWNTs show low cytotoxicity in both cells with
      insignificant effects on the cell proliferation rates. However, both PTX loaded
      PEG-g-SWNTs and PTX loaded PEG-g-MWNTs show high efficacy to kill HeLa cells and
      MCF-7 cells, as reflected by IC(50) lower than free PTX. Therefore, PTX loaded
      PEG-g-CNTs are promising for cancer therapeutics. KEYWORDS: carbon nanotubes,
      poly(ethylene glycol), drug delivery, cancer therapy, nanomedicine.

PMID- 20057025
TI  - Zinc sulfide nanowire arrays on silicon wafers for field emitters.
AB  - Wurtzite structured zinc sulfide (ZnS) nanowire arrays are synthesized on silicon
      (111) wafers by a facile evaporation-condensation approach. These ZnS nanowire
      arrays possess predominant field emission properties with a low turn-on field of
      2.9 V microm(-1), a low threshold field of 4.25 V microm(-1), a high field
      enhancement factor (over 2700), and a high stability with a low fluctuation
      (approximately 0.8%). The improved field emission performance of these ZnS
      nanowire arrays is attributed to their specific crystallographic feature-array
      structures with nanotips and high single crystallinity. These results suggest
      that such ZnS nanowire arrays can be used as building blocks for field emitters.

PMID- 20057026
TI  - Abnormal gas sensing characteristics arising from catalyzed morphological changes
      of ionsorbed oxygen.
AB  - Abnormal gas sensing characteristics are observed at low temperature in uniformly
      loaded Pt@SnO(2) nanorod gas sensors. The sensors operated at 200 degrees C
      exhibit opposite variations of resistances, and the change of resistance
      decreases with increasing ethanol concentration. In contrast, the sensors
      operated at 300 degrees C show regular behavior and the sensitivity is extremely
      high. Such behaviors are ascribed to Pt-catalyzed morphological changes of
      ionsorbed oxygen at low temperature. The present results are the bases for
      further investigating the effect of ionsorbed oxygen morphologies on gas sensing.

PMID- 20057027
TI  - Bundles of polytwins as meta-elastic domains in the thin polycrystalline simple
      multi-ferroic system PZT.
AB  - We used enhanced piezo-response force microscopy (E-PFM) to investigate both
      ferroelastic and ferroelectric nanodomains in thin films of the simple multi
      ferroic system PbZr(0.3)Ti(0.7)O(3) (PZT). We show how the grains are organized
      into a new type of elastic domain bundles of the well-known periodic elastic
      twins. Here we present these bundle domains and discuss their stability and
      origin. Moreover, we show that they can arrange in such a way as to release
      strain in a more effective way than simple twinning. Finally, we show that these
      bundle domains can arrange to form the macroscopic ferroelectric domains that
      constitute the basis of ferroelectric-based memory devices.

PMID- 20057028
TI  - Growth, structure and magnetic properties of FePt nanostructures on NaCl(001) and
      MgO(001).
AB  - A comparison of the structural and magnetic properties of FePt nanostructures
      grown at different temperatures on NaCl(001) and MgO(001) substrates is
      presented. A strong influence of the deposition temperature on the epitaxial
      growth as well as on the size distribution of FePt nanostructures grown on NaCl
      substrates is observed. In spite of a large lattice mismatch between FePt and
      NaCl, a 'cube-over-cube' growth of nanostructures with a narrow size distribution
      was achieved at 520 K. Moreover, the growth of FePt nanostructures on NaCl(001)
      is not preceded by the formation of a wetting layer as observed on MgO(001). The
      higher degree of L1(0) chemical ordering in FePt nanostructures grown on MgO(001)
      accompanied by the absence of L1(0) variants with an in-plane tetragonal c-axis
      indicates that the tensile epitaxial stress induced by the MgO substrate is a key
      factor in the formation of the L1(0) phase with an out-of-plane c-axis.
      Superparamagnetic behavior is revealed for the FePt nanostructures grown on
      NaCl(001) due to their small size and relatively poor chemical order.

PMID- 20057029
TI  - The enhancement of photoresponse of an ordered inorganic-organic hybrid
      architecture by increasing interfacial contacts.
AB  - A modified ZnO quantum dot/polythiophene (ZnO/PTh) inorganic-organic hybrid
      architecture was fabricated by using ordered mesoporous silica (SBA-15) as the
      retaining template. First, a two-step strategy was developed to synthesize an
      ordered organic conducting polymer composite (PTh/SBA-15). Then, ZnO quantum dots
      were in situ formed on the pore walls of the ordered PTh/SBA-15 composite.
      Photoresponse of the inorganic-organic hybrid was studied with respect to its
      incident photon to collected electron conversion efficiency (IPCE) and
      morphology. The presence of SBA-15 proved to be critical for controlling the
      interfacial morphology and hence enlarging the interfacial area of the inorganic
      organic heterojunction. The proposed approach may act as a key method to open up
      potential applications in photovoltaic devices.

PMID- 20057030
TI  - The use of microwave plasma-assisted CVD on nanostructured iron catalysts to grow
      isolated bundles of carbon nanotubes.
AB  - Catalysts play a key role in the growth of carbon nanotubes. The microwave plasma
      assisted chemical vapor deposition (MPACVD) method is now commonly used for
      directional and conformal growth of carbon nanotubes (CNTs) on substrates. In
      this work, we report on the effect of H(2) plasma pre-treatment on the diameter
      and density of iron catalyst nanoparticles for different iron layer thicknesses
      in order to grow isolated bundles of CNTs. Atomic force microscopy shows first
      that as plasma power density increases, iron nanoparticle diameters decrease,
      which is due to the increasing of gas dissociation giving more ion bombardment
      energy, and second that the diameter of nanoparticles decreases with the catalyst
      thickness. The growth of CNT was carried out under different CH(4) concentrations
      for different iron film thicknesses. Transmission electron microscopy and Raman
      spectroscopy show that the synthesized CNT were of good quality and had an outer
      diameter between 5 and 10 nm.

PMID- 20057031
TI  - Tailoring gold nanostructures for near-field optical applications.
AB  - A method of combined thin-film deposition, electron beam lithography, and ion
      milling is presented for the fabrication of gold and silver nanostructures. The
      flexibility of lithographical processes for the variation of geometric parameters
      is combined with three-dimensional control over the surface evolution. Depending
      on the etching angle, different shapes ranging from cones over rods to cups can
      be achieved. These size- and shape-tunable structures present a toolbox for nano
      optical investigations. As an example, optical properties of systematically
      varying structures are examined in a parabolic mirror confocal microscope.

PMID- 20057032
TI  - Conductive AFM microscopy study of the carrier transport and storage in Ge
      nanocrystals grown by dewetting.
AB  - A combined conductive atomic force microscope (C-AFM)/scanning electron
      microscope (SEM) has been used to study the electric transport and retention
      mechanisms through Ge nanocrystals (NCs). The NCs were formed by a two-step
      dewetting/nucleation process on a silicon oxide layer grown on n-doped 001
      silicon substrate. Without preliminary e-beam irradiation, electric images are
      obtained only with bias voltages larger than 8 V. This is due to the barrier
      height introduced by the presence of the native oxide on NCs and of the oxide
      layer on which the NCs are grown. After acquisition of an e-beam-induced current
      image, electric images (e-beam off) can be easily obtained at low bias voltages
      because of the trap creation in the oxide layer. We show that the critical
      threshold voltage to detect a current through the NCs decreases with NCs size.
      The band diagram of the contact in the presence of a p-doped diamond coated tip
      shows that the conduction mechanism is dominated by holes. At last we show a good
      memory effect with charge/discharge in the NCs resulting in a long retention
      time.

PMID- 20057033
TI  - Tuning the electronic structure and transport properties of graphene by
      noncovalent functionalization: effects of organic donor, acceptor and metal
      atoms.
AB  - Using density functional theory and nonequilibrium Green's function (NEGF)
      formalism, we have theoretically investigated the binding of organic donor,
      acceptor and metal atoms on graphene sheets, and revealed the effects of the
      different noncovalent functionalizations on the electronic structure and
      transport properties of graphene. The adsorptions of 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ) and tetrathiafulvalene (TTF) induce hybridization between the
      molecular levels and the graphene valence bands, and transform the zero-gap
      semiconducting graphene into a metallic graphene. However, the current versus
      voltage (I-V) simulation indicates that the noncovalent modifications by organic
      molecules are not sufficient to significantly alter the transport property of the
      graphene for sensing applications. We found that the molecule/graphene
      interaction could be dramatically enhanced by introducing metal atoms to
      construct molecule/metal/graphene sandwich structures. A chemical sensor based on
      iron modified graphene shows a sensitivity two orders of magnitude higher than
      that of pristine graphene. The results of this work could help to design novel
      graphene-based sensing or switching devices.

PMID- 20057034
TI  - The fabrication of carbon-nanotube-coated electrodes and a field-emission-based
      luminescent device.
AB  - Tungsten substrates were coated with an Ni or Ni-Co catalyst by the electroless
      dip coating technique. Various carbon nanotubes were synthesized by the catalytic
      chemical vapor deposition (CVD) method under different growth conditions. It was
      observed that Ni-and Ni-Co-coated tungsten substrates give very good growth of
      carbon nanotubes (CNT) in terms of yield, uniformity and alignment at a growth
      temperature of 600 degrees C. We fabricated a field-emission-based luminescent
      light bulb where a tungsten wire coated with carbon nanotubes served as a
      cathode. Results show lower threshold voltage, better emission stability and
      higher luminescence for CNT cathodes in comparison with uncoated tungsten
      cathodes. We found that aligned-coiled carbon nanotubes are superior to straight
      CNTs in terms of field emission characteristics and luminescence properties.

PMID- 20057035
TI  - Fullerene monolayer formation by spray coating.
AB  - Many large molecular complexes are limited in thin film applications by their
      insufficient thermal stability, which excludes deposition via commonly used
      vapour phase deposition methods. Here we demonstrate an alternative way of
      monolayer formation of large molecules by a simple spray coating method under
      ambient conditions. This technique has been successfully applied on C(60)
      dissolved in toluene and carbon disulfide. Monolayer thick C(60) films have been
      formed on graphite and gold surfaces at particular deposition parameters, as
      confirmed by atomic force and scanning tunnelling microscopies. Structural and
      electronic properties of spray coated C(60) films on Au(111) have been found
      comparable to thermally evaporated C(60). We attribute the monolayer formation in
      spray coating to a crystallization process mediated by an ultrathin solution film
      on a sample surface.

PMID- 20057036
TI  - Effective electron collection in highly (110)-oriented ZnO porous nanosheet
      framework photoanode.
AB  - A highly (110)-oriented ZnO porous nanosheet framework is designed as the
      photoanode in photoelectrochemical systems, by virtue of its anisotropic
      electronic properties. It can be facilely prepared in large scale via a
      hydrothermal method. X-ray diffraction (XRD) analyses show that the orientation
      index of the (110) diffraction plane is 3.54, indicating the films possess (110)
      preferred orientation. Field-emission scanning electron microscope (FE-SEM)
      images exhibit that most of the nanosheets stand nearly perpendicularly on the
      substrate. The {002} lattice planes work just like conducting wires and induce
      the electrons to transport to the substrate. Chronoamperometry measurement
      demonstrates an effective electron collection. When the nanostructured photoanode
      is introduced to dye-sensitized solar cells, a conversion efficiency of 3.7% is
      obtained. The photoanode also has potential application in the other
      photoelectrochemical systems, such as photocatalytical splitting of water.

PMID- 20057037
TI  - Direct ArF laser photopatterning of metal oxide nanostructures prepared by the
      sol-gel route.
AB  - We developed specific negative tone resists suitable for preparing periodic
      inorganic nanostructures by ArF photolithography. This approach is based on the
      sol-gel chemistry of modified metal alkoxides followed by DUV laser irradiation.
      Patterning at the nanoscale was demonstrated by using an achromatic
      interferometer operating at 193 nm. In a second step, thermal treatment could be
      used to obtain metal oxide nanostructures (ZrO(2), TiO(2)). Such thermal
      treatment did not affect the integrity of the nanostructures. The DUV-induced
      modifications of the physico-chemical properties of the sol-gel thin film were
      followed by ellipsometry, XPS and AFM. The crystalline structure of the material
      after thermal treatment was proved by DRX analysis. Examples of periodic
      nanostructures are given in order to illustrate the possibilities opened by this
      new route that provides a convenient method to create transparent, robust, high
      refractive index nanostructures compatible with a wide variety of substrates.

PMID- 20057038
TI  - First-principles investigation of electrochemical properties of gold
      nanoparticles.
AB  - A first-principles formalism is employed to investigate the effects of size and
      structure on the electronic and electrochemical properties of Au nanoparticles
      with diameters between 0.8 and 2.0 nm. We find that the behavior of the
      ionization potentials (IPs) and the electron affinities (EAs) as a function of
      cluster size can be separated into many-body and single-electron contributions.
      The many-body part is only (and continuously) dependent on particle size, and can
      be very well described in terms of the capacitance of classical spherical
      conductors for clusters with more the 55 atoms. For smaller clusters, molecule
      like features lead the capacitance and fundamental gap to differ systematically
      from those of a classical conductor with decreasing size. The single-electron
      part fluctuates with particle structure. Upon calculating the neutral chemical
      potential micro(0) = (IP+EA)/2, the many-body contributions cancel out, resulting
      in fluctuations of micro(0) around the bulk Au work function, consistent with
      experimental results. The values of IP and EA changes upon functionalization with
      thiolated molecules, and the magnitude of the observed changes does not depend on
      the length of the alkane chain. The functionalization can also lead to a
      transition from metallic to non-metallic behavior in small nanoparticles, which
      is consistent with experimental observations.

PMID- 20057039
TI  - Electronic and transport properties of a molecular junction with asymmetric
      contacts.
AB  - Asymmetric molecular junctions have been shown experimentally to exhibit a dual
      conductance transport property with a pulse-like current-voltage characteristic,
      by Reed and co-workers. Using a recently developed first-principles integrated
      piecewise thermal equilibrium current calculation method and a gold-benzene-1
      olate-4-thiolate-gold model molecular junction, this unusual transport property
      has been reproduced. Analysis of the electrostatics and the electronic structure
      reveals that the high-current state results from subtle bias induced charge
      transfer at the electrode-molecule contacts that raises molecular orbital
      energies and enhances the current-contributing molecular density of states and
      the probabilities of resonance tunneling of conduction electrons from one
      electrode to another.

PMID- 20057040
TI  - Modelling and fabrication of GaAs photonic-crystal cavities for cavity quantum
      electrodynamics.
AB  - In this paper, we present recent progress in the growth, modelling, fabrication
      and characterization of gallium arsenide (GaAs) two-dimensional (2D) photonic
      crystal slab cavities with embedded indium arsenide (InAs) quantum dots (QDs)
      that are designed for cavity quantum electrodynamics (cQED) experiments. Photonic
      crystal modelling and device fabrication are discussed, followed by a detailed
      discussion of different failure modes that lead to photon loss. It is found that,
      along with errors introduced during fabrication, other significant factors such
      as the presence of a bottom substrate and cavity axis orientation with respect to
      the crystal axis, can influence the cavity quality factor (Q). A useful
      diagnostic tool in the form of contour finite-difference time domain (FDTD) is
      employed to analyse device performance.

PMID- 20057041
TI  - Ultrathin ZnO nanorods: facile synthesis, characterization and optical
      properties.
AB  - We first took advantage of a modified solvothermal route to achieve deliberate
      size modulation of ZnO nanorods. In this facile wet chemical process, the crystal
      sizes are sensitive to the surfactant concentrations, due to the efficient
      selecting adsorption of surfactant on the ZnO crystal planes. As a result, a fine
      size tuning of ZnO nanorods (from about 6.5 nm to about 120 nm) with high quality
      is conveniently achieved. The as-prepared ultrathin ZnO nanorods were
      investigated using scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and x-ray diffraction. Optical properties of the ultrathin ZnO
      nanorods were also studied; the strong UV excitonic emission and weak deep-level
      emission reveal their very limited structural defects and narrow size
      distribution, which is interesting and important for facilitating their special
      applications for photoelectric nanodevices in modern science and technology.

PMID- 20057042
TI  - Black sheep among the flock of protein structures.

PMID- 20057043
TI  - Feasibility of one-shot-per-crystal structure determination using Laue
      diffraction.
AB  - Crystal size is an important factor in determining the number of diffraction
      patterns which may be obtained from a protein crystal before severe radiation
      damage sets in. As crystal dimensions decrease this number is reduced, eventually
      falling to one, at which point a complete data set must be assembled using data
      from multiple crystals. When only a single exposure is to be collected from each
      crystal, the polychromatic Laue technique may be preferable to monochromatic
      methods owing to its simultaneous recording of a large number of fully recorded
      reflections per image. To assess the feasibility of solving structures using
      single Laue images from multiple crystals, data were collected using a 'pink'
      beam at the CHESS D1 station from groups of lysozyme crystals with dimensions of
      the order of 20-30 microm mounted on MicroMesh grids. Single-shot Laue data were
      used for structure determination by molecular replacement and correct solutions
      were obtained even when as few as five crystals were used.

PMID- 20057044
TI  - MolProbity: all-atom structure validation for macromolecular crystallography.
AB  - MolProbity is a structure-validation web service that provides broad-spectrum
      solidly based evaluation of model quality at both the global and local levels for
      both proteins and nucleic acids. It relies heavily on the power and sensitivity
      provided by optimized hydrogen placement and all-atom contact analysis,
      complemented by updated versions of covalent-geometry and torsion-angle criteria.
      Some of the local corrections can be performed automatically in MolProbity and
      all of the diagnostics are presented in chart and graphical forms that help guide
      manual rebuilding. X-ray crystallography provides a wealth of biologically
      important molecular data in the form of atomic three-dimensional structures of
      proteins, nucleic acids and increasingly large complexes in multiple forms and
      states. Advances in automation, in everything from crystallization to data
      collection to phasing to model building to refinement, have made solving a
      structure using crystallography easier than ever. However, despite these
      improvements, local errors that can affect biological interpretation are
      widespread at low resolution and even high-resolution structures nearly all
      contain at least a few local errors such as Ramachandran outliers, flipped
      branched protein side chains and incorrect sugar puckers. It is critical both for
      the crystallographer and for the end user that there are easy and reliable
      methods to diagnose and correct these sorts of errors in structures. MolProbity
      is the authors' contribution to helping solve this problem and this article
      reviews its general capabilities, reports on recent enhancements and usage, and
      presents evidence that the resulting improvements are now beneficially affecting
      the global database.

PMID- 20057045
TI  - Molecular replacement with MOLREP.
AB  - MOLREP is an automated program for molecular replacement that utilizes a number
      of original approaches to rotational and translational search and data
      preparation. Since the first publication describing the program, MOLREP has
      acquired a variety of features that include weighting of the X-ray data and
      search models, multi-copy search, fitting the model into electron density,
      structural superposition of two models and rigid-body refinement. The program can
      run in a fully automatic mode using optimized parameters calculated from the
      input data.

PMID- 20057046
TI  - Overcoming merohedral twinning in crystals of bacteriorhodopsin grown in lipidic
      mesophase.
AB  - Twinning is one of the most common crystal-growth defects in protein
      crystallography. There are neither efficient rational approaches for the growth
      of nontwinned protein crystals nor are there examples of systematic studies of
      the dependence of the twinning-ratio distribution on crystallization conditions.
      The description of the twinning phenomenon has been covered even less for
      membrane-protein crystals and is non-existent for crystals grown using lipidic
      phases (in meso). In the present work, possibilities for overcoming merohedral
      twinning are investigated for crystals of the membrane protein bacteriorhodopsin
      (bR) grown in meso. It is shown that traditional crystallization additives are
      not effective in the case of the in meso crystallization of bR. The twinning
      ratio was determined for 310 crystals grown under different crystallization
      conditions. A correlation of the twinning ratio with the growth rate of the
      crystals was observed. Slow growth indicated that crystals had a noticeable
      chance of avoiding twinning. Model calculations were performed in order to
      rationalize this observation. The calculations confirmed the experimental
      observation that most crystals consist of two twin domains and showed that under
      this condition small changes in the probability of twin-domain formation lead to
      dramatic changes in the number of nontwinned crystals, which explains why slow
      crystal growth results in a considerable number of nontwinned crystals.

PMID- 20057047
TI  - Structure of a family 3b' carbohydrate-binding module from the Cel9V glycoside
      hydrolase from Clostridium thermocellum: structural diversity and implications
      for carbohydrate binding.
AB  - Family 3 carbohydrate-binding modules (CBM3s) are associated with both
      cellulosomal scaffoldins and family 9 glycoside hydrolases (GH9s), which are
      multi-modular enzymes that act on cellulosic substrates. CBM3s bind cellulose. X
      ray crystal structures of these modules have established an accepted cellulose
      binding mechanism based on stacking interactions between the sugar rings of
      cellulose and a planar array of aromatic residues located on the CBM3 surface.
      These planar-strip residues are generally highly conserved, although some CBM3
      sequences lack one or more of these residues. In particular, CBM3b' from
      Clostridium thermocellum Cel9V exhibits such sequence changes and fails to bind
      cellulosic substrates. A crystallographic investigation of CBM3b' has been
      initiated in order to understand the structural reason(s) for this inability.
      CBM3b' crystallized in space group C222(1) (diffraction was obtained to 2.0 A
      resolution in-house) with three independent molecules in the asymmetric unit and
      in space group P4(1)2(1)2 (diffraction was obtained to 1.79 A resolution in-house
      and to 1.30 A resolution at a synchrotron) with one molecule in the asymmetric
      unit. The molecular structure of Cel9V CBM3b' revealed that in addition to the
      loss of several cellulose-binding residues in the planar strip, changes in the
      backbone create a surface 'hump' which could interfere with the formation of
      cellulose-protein surface interactions and thus prevent binding to crystalline
      cellulose.

PMID- 20057048
TI  - Self-interaction chromatography as a tool for optimizing conditions for membrane
      protein crystallization.
AB  - The second virial coefficient, or B value, is a measurement of how well a protein
      interacts with itself in solution. These interactions can lead to protein
      crystallization or precipitation, depending on their strength, with a narrow
      range of B values (the 'crystallization slot') being known to promote
      crystallization. A convenient method of determining the B value is by self
      interaction chromatography. This paper describes how the light-harvesting complex
      1-reaction centre core complex from Allochromatium vinosum yielded single
      straight-edged crystals after iterative cycles of self-interaction chromatography
      and crystallization. This process allowed the rapid screening of small molecules
      and detergents as crystallization additives. Here, a description is given of how
      self-interaction chromatography has been utilized to improve the crystallization
      conditions of a membrane protein.

PMID- 20057049
TI  - The X-ray structure of Salmonella typhimurium uridine nucleoside phosphorylase
      complexed with 2,2'-anhydrouridine, phosphate and potassium ions at 1.86 A
      resolution.
AB  - Uridine nucleoside phosphorylase is an important drug target for the development
      of anti-infective and antitumour agents. The X-ray crystal structure of
      Salmonella typhimurium uridine nucleoside phosphorylase (StUPh) complexed with
      its inhibitor 2,2'-anhydrouridine, phosphate and potassium ions has been solved
      and refined at 1.86 A resolution (R(cryst) = 17.6%, R(free) = 20.6%). The complex
      of human uridine phosphorylase I (HUPhI) with 2,2'-anhydrouridine was modelled
      using a computational approach. The model allowed the identification of atomic
      groups in 2,2'-anhydrouridine that might improve the interaction of future
      inhibitors with StUPh and HUPhI.

PMID- 20057050
TI  - The structure of dihydrodipicolinate reductase (DapB) from Mycobacterium
      tuberculosis in three crystal forms.
AB  - Dihydrodipicolinate reductase (DHDPR, DapB) is an enzyme that belongs to the L
      lysine biosynthetic pathway. DHDPR reduces the alpha,beta-unsaturated cyclic
      imine 2,3-dihydrodipicolinic acid to yield the compound 2,3,4,5
      tetrahydrodipicolinic acid in a pyridine nucleotide-dependent reaction. The
      substrate of this reaction is the unstable product of the preceding enzyme
      dihydrodipicolinate synthase (DHDPS, DapA). Here, the structure of apo-DHDPR from
      Mycobacterium tuberculosis is reported in two orthorhombic crystal forms, as well
      as the structure of DHDPR from M. tuberculosis in complex with NADH in a
      monoclinic crystal form. A comparison of the results with previously solved
      structures of this enzyme shows that DHDPR undergoes a major conformational
      change upon binding of its cofactor. This conformational change can be
      interpreted as one of the low-frequency normal modes of the structure.

PMID- 20057051
TI  - Adenosine binding to low-molecular-weight purine nucleoside phosphorylase: the
      structural basis for recognition based on its complex with the enzyme from
      Schistosoma mansoni.
AB  - Schistosomes are unable to synthesize purines de novo and depend exclusively on
      the salvage pathway for their purine requirements. It has been suggested that
      blockage of this pathway could lead to parasite death. The enzyme purine
      nucleoside phosphorylase (PNP) is one of its key components and molecules
      designed to inhibit the low-molecular-weight (LMW) PNPs, which include both the
      human and schistosome enzymes, are typically analogues of the natural substrates
      inosine and guanosine. Here, it is shown that adenosine both binds to Schistosoma
      mansoni PNP and behaves as a weak micromolar inhibitor of inosine phosphorolysis.
      Furthermore, the first crystal structures of complexes of an LMW PNP with
      adenosine and adenine are reported, together with those with inosine and
      hypoxanthine. These are used to propose a structural explanation for the
      selective binding of adenosine to some LMW PNPs but not to others. The results
      indicate that transition-state analogues based on adenosine or other 6-amino
      nucleosides should not be discounted as potential starting points for alternative
      inhibitors.

PMID- 20057052
TI  - Structural analysis of an MK2-inhibitor complex: insight into the regulation of
      the secondary structure of the Gly-rich loop by TEI-I01800.
AB  - Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK2) is
      a Ser/Thr kinase from the p38 mitogen-activated protein kinase signalling pathway
      and plays an important role in inflammatory diseases. The crystal structure of
      the complex of human MK2 (residues 41-364) with the potent MK2 inhibitor TEI
      I01800 (pK(i) = 6.9) was determined at 2.9 A resolution. The MK2 structure in the
      MK2-TEI-I01800 complex is composed of two domains, as observed for other Ser/Thr
      kinases; however, the Gly-rich loop in the N-terminal domain forms an alpha-helix
      structure and not a beta-sheet. TEI-I01800 binds to the ATP-binding site as well
      as near the substrate-binding site of MK2. Both TEI-I01800 molecules have a
      nonplanar conformation that differs from those of other MK2 inhibitors deposited
      in the Protein Data Bank. The MK2-TEI-I01800 complex structure is the first
      active MK2 with an alpha-helical Gly-rich loop and TEI-I01800 regulates the
      secondary structure of the Gly-rich loop.

PMID- 20057053
TI  - Two crystal modifications of (Pro-Pro-Gly)4-Hyp-Hyp-Gly-(Pro-Pro-Gly)4 reveal the
      puckering preference of Hyp(X) in the Hyp(X):Hyp(Y) and Hyp(X):Pro(Y) stacking
      pairs in collagen helices.
AB  - Two crystal modifications of a collagen model peptide, (Pro-Pro-Gly)(4)-Hyp-Hyp
      Gly-(Pro-Pro-Gly)(4) [where Hyp is (4R,2S)-L-hydroxyproline], showed very similar
      unit-cell parameters and belonged to the same space group P2(1). Both crystals
      exhibited pseudo-merohedral twinning. The main difference was in their molecular
      packing arrangements. One modification showed pseudo-hexagonal packing, while the
      other showed pseudo-tetragonal packing. Despite their different packing
      arrangements, no significant differences were observed in the hydration states of
      these modifications. The peptide in the pseudo-tetragonal crystal showed a cyclic
      fluctuation of helical twists with a period of 20 A, while that in the pseudo
      hexagonal crystal did not. In these modifications, the puckering conformations of
      four of the 12 Hyp residues at the X position of the Hyp(X)-Hyp(Y)-Gly sequence
      were in the opposite conformations to the previous hypothesis that Hyp(X)
      residues involved in Hyp(X):Hyp(Y) and Hyp(X):Pro(Y) stacking pairs prefer up
      puckering and down-puckering conformations, respectively. Detailed investigation
      of the molecular interactions between Hyp(X) and adjacent molecules revealed that
      these opposite conformations appeared because the puckering conformation, which
      follows the hypothesis, is subject to steric hindrance from the adjacent
      molecule.

PMID- 20057054
TI  - A toolkit for the characterization of CCD cameras for transmission electron
      microscopy.
AB  - Charge-coupled devices (CCD) are nowadays commonly utilized in transmission
      electron microscopy (TEM) for applications in life sciences. Direct access to
      digitized images has revolutionized the use of electron microscopy, sparking
      developments such as automated collection of tomographic data, focal series,
      random conical tilt pairs and ultralarge single-particle data sets. Nevertheless,
      for ultrahigh-resolution work photographic plates are often still preferred. In
      the ideal case, the quality of the recorded image of a vitrified biological
      sample would solely be determined by the counting statistics of the limited
      electron dose the sample can withstand before beam-induced alterations dominate.
      Unfortunately, the image is degraded by the non-ideal point-spread function of
      the detector, as a result of a scintillator coupled by fibre optics to a CCD, and
      the addition of several inherent noise components. Different detector
      manufacturers provide different types of figures of merit when advertising the
      quality of their detector. It is hard for most laboratories to verify whether all
      of the anticipated specifications are met. In this report, a set of algorithms is
      presented to characterize on-axis slow-scan large-area CCD-based TEM detectors.
      These tools have been added to a publicly available image-processing toolbox for
      MATLAB. Three in-house CCD cameras were carefully characterized, yielding, among
      others, statistics for hot and bad pixels, the modulation transfer function, the
      conversion factor, the effective gain and the detective quantum efficiency. These
      statistics will aid data-collection strategy programs and provide prior
      information for quantitative imaging. The relative performance of the
      characterized detectors is discussed and a comparison is made with similar
      detectors that are used in the field of X-ray crystallography.

PMID- 20057056
TI  - Crystals on the cover and validation reports.

PMID- 20057057
TI  - Role of tyrosine 131 in the active site of paAzoR1, an azoreductase with
      specificity for the inflammatory bowel disease prodrug balsalazide.
AB  - Azoreductase 1 from Pseudomonas aeruginosa strain PAO1 (paAzoR1) catalyses the
      activation of the prodrug balsalazide and reduces the azo dye methyl red using
      reduced nicotinamide adenine dinucleotide cofactor as an electron donor. To
      investigate the mechanism of the enzyme, a Y131F mutation was introduced and the
      enzymic properties of the mutant were compared with those of the wild-type
      enzyme. The crystallographic structure of the mutant with methyl red bound was
      solved at 2.1 A resolution and compared with the wild-type structure. Tyr131 is
      important in the architecture of the active site but is not essential for enzymic
      activity.

PMID- 20057058
TI  - Structure of YqgQ protein from Bacillus subtilis, a conserved hypothetical
      protein.
AB  - The crystal structure of the hypothetical protein YqgQ from Bacillus subtilis has
      been determined to 2.1 A resolution. The crystals belonged to space group P2(1),
      with unit-cell parameters a = 51.85, b = 41.25, c = 55.18 A, beta = 113.4 degrees
      , and contained three protein molecules in the asymmetric unit. The structure was
      determined by the single-wavelength anomalous dispersion method using selenium
      labeled protein and was refined to a final R factor of 24.7% (R(free) = 28.0%).
      The protein molecule mainly comprises a three-helical bundle. Its putative
      function is inferred to be single-stranded nucleic acid binding based on sequence
      and structural homology.

PMID- 20057059
TI  - Cloning, recombinant production, crystallization and preliminary X-ray
      diffraction analysis of SDF2-like protein from Arabidopsis thaliana.
AB  - The stromal-cell-derived factor 2-like protein of Arabidopsis thaliana (AtSDL)
      has been shown to be highly up-regulated in response to unfolded protein response
      (UPR) inducing reagents, suggesting that it plays a crucial role in the plant UPR
      pathway. AtSDL has been cloned, overexpressed, purified and crystallized using
      the vapour-diffusion method. Two crystal forms have been obtained under very
      similar conditions. The needle-shaped crystals did not diffract X-rays, while the
      other form diffracted to 1.95 A resolution using a synchrotron-radiation source
      and belonged to the hexagonal space group P6(1), with unit-cell parameters a = b
      = 96.1, c = 69.3 A.

PMID- 20057060
TI  - Crystallization and preliminary X-ray diffraction analysis of the MIF4G domain of
      DAP5.
AB  - Death-associated protein 5 (DAP5) is a member of the eIF4G family of scaffolding
      proteins that mediate cap-independent translation initiation by recruiting the
      translational machinery to internal ribosomal entry sites (IRESs) on mRNA. The
      MIF4G domain of DAP5 directly interacts with the eukaryotic initiation factors
      eIF4A and eIF3 and enhances the translation of several viral and cellular IRESs.
      Here, the crystallization and preliminary X-ray diffraction analysis of the MIF4G
      domain of DAP5 is presented.

PMID- 20057061
TI  - Cloning, purification, crystallization and preliminary X-ray crystallographic
      analysis of MCAT from Staphylococcus aureus.
AB  - Malonyl-CoA:acyl-carrier protein transacylase (MCAT), encoded by the fabd gene,
      is a key enzyme in type II fatty-acid biosynthesis. It is responsible for
      transferring the malonyl group from malonyl-CoA to the holo acyl-carrier protein
      (ACP). Since the type II system differs from the type I system that mammals use,
      it has received enormous attention as a possible antibiotic target. In
      particular, only a single isoform of MCAT has been reported and a continuous
      coupled enzyme assay has been developed. MCAT from Staphylococcus aureus was
      overexpressed in Escherichia coli and the protein was purified and crystallized.
      Diffraction data were collected to 1.2 A resolution. The crystals belonged to
      space group P2(1), with unit-cell parameters a = 41.608, b = 86.717, c = 43.163
      A, alpha = gamma = 90, beta = 106.330 degrees . The asymmetric unit contains one
      SaMCAT molecule.

PMID- 20057062
TI  - Crystallization and preliminary X-ray analysis of NADH:rubredoxin oxidoreductase
      from Clostridium acetobutylicum.
AB  - NADH:rubredoxin oxidoreductase (NROR), an O(2)-inducible protein, is a versatile
      electron donor for scavengers of O(2) and reactive oxygen species (ROS) in
      Clostridium acetobutylicum. Recombinant NROR was overexpressed in Escherichia
      coli and purified to homogeneity; it was subsequently crystallized using the
      sitting-drop vapour-diffusion method at 293 K. Preliminary crystallographic
      analysis revealed that the crystals belonged to space group P4(1)22 or P4(3)22,
      with unit-cell parameters a = b = 98.6, c = 88.3 A, and diffracted to 2.1 A
      resolution. Assuming that the crystals contained one molecule per asymmetric
      unit, the Matthews coefficient was calculated to be 2.7 A(3) Da(-1) and the
      solvent content to be 54.1%.

PMID- 20057063
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of Cif,
      a virulence factor secreted by Pseudomonas aeruginosa.
AB  - The opportunistic pathogen Pseudomonas aeruginosa secretes a protein that
      triggers the accelerated degradation of the cystic fibrosis transmembrane
      conductance regulator (CFTR) in airway epithelial cells. This protein, which is
      known as the CFTR inhibitory factor (Cif), acts as a virulence factor and may
      facilitate airway colonization by P. aeruginosa. Based on sequence similarity Cif
      appears to be an epoxide hydrolase (EH), but it lacks several of the conserved
      features found in the active sites of canonical members of the EH family. Here,
      the crystallization of purified recombinant Cif by vapor diffusion is reported.
      The crystals formed in space group C2, with unit-cell parameters a = 167.4, b =
      83.6, c = 88.3 A, beta = 100.6 degrees . The crystals diffracted to 2.39 A
      resolution on a rotating-anode source. Based on the calculated Matthews
      coefficient (2.2 A(3) Da(-1)), it appears that the asymmetric unit contains four
      molecules.

PMID- 20057064
TI  - Crystallization and X-ray diffraction analysis of human CLEC5A (MDL-1), a dengue
      virus receptor.
AB  - The human C-type lectin-like protein CLEC5A (also known as MDL-1) is expressed on
      the surface of myeloid cells and plays a critical role in dengue-virus-induced
      disease by signalling through the transmembrane adaptor protein DAP12. The C-type
      lectin-like domain of CLEC5A was expressed in Escherichia coli, refolded and
      purified. Recombinant CLEC5A crystals were grown by sitting-drop vapour diffusion
      using polyethylene glycol 6000 as a precipitant. After optimization, crystals
      were grown which diffracted to 1.56 A using synchrotron radiation. The results
      presented in this paper suggest that crystals producing diffraction of this
      quality will be suitable for structural determination of human CLEC5A.

PMID- 20057065
TI  - Crystallization of dihydrodipicolinate synthase from a clinical isolate of
      Streptococcus pneumoniae.
AB  - Dihydrodipicolinate synthase (DHDPS; EC 4.2.1.52) catalyzes the rate-limiting
      step in the (S)-lysine biosynthesis pathway of bacteria and plants. Here, the
      cloning of the DHDPS gene from a clinical isolate of Streptococcus pneumoniae
      (OXC141 strain) and the strategy used to express, purify and crystallize the
      recombinant enzyme are described. Diffracting crystals were grown in high
      molecular-weight PEG precipitants using the hanging-drop vapour-diffusion method.
      The best crystal, from which data were collected, diffracted to beyond 2.0 A
      resolution. Initially, the crystals were thought to belong to space group
      P4(2)2(1)2, with unit-cell parameters a = 105.5, b = 105.5, c = 62.4 A. However,
      the R factors remained high following initial processing of the data. It was
      subsequently shown that the data set was twinned and it was thus reprocessed in
      space group P2, resulting in a significant reduction in the R factors.
      Determination of the structure will provide insight into the design of novel
      antimicrobial agents targeting this important enzyme from S. pneumoniae.

PMID- 20057066
TI  - Crystallization and preliminary X-ray diffraction analysis of diaminopimelate
      epimerase from Escherichia coli.
AB  - Diaminopimelate (DAP) epimerase (EC 5.1.1.7) catalyzes the penultimate step of
      lysine biosynthesis in bacteria and plants, converting L,L-diaminopimelate to
      meso-diaminopimelate. Here, the cloning, expression, purification,
      crystallization and preliminary X-ray diffraction analysis of DAP epimerase from
      Escherichia coli are presented. Crystals were obtained in space group P4(1)2(1)2
      and diffracted to 2.0 A resolution, with unit-cell parameters a = b = 89.4, c =
      179.6 A. Molecular replacement was conducted using Bacillus anthracis DAP
      epimerase as a search model and showed the presence of two molecules in the
      asymmetric unit, with an initial R(free) of 0.456 and R(work) of 0.416.

PMID- 20057067
TI  - Crystallization and preliminary X-ray crystallographic analysis of the N domain
      of p97/VCP in complex with the UBX domain of FAF1.
AB  - p97/VCP is a multifunctional AAA(+)-family ATPase that is involved in diverse
      cellular processes. p97/VCP directly interacts with various adaptors for activity
      in different biochemical contexts. Among these adaptors are p47 and Fas
      associated factor 1 (FAF1), which contain a common UBX domain through which they
      bind to the N domain of p97/VCP. In the ubiquitin-proteasome pathway, p97/VCP
      acts as a chaperone that presents client proteins to the proteasome for
      degradation, while FAF1 modulates the process by interacting with ubiquitinated
      client proteins and also with p97/VCP. In an effort to elucidate the structural
      details of the interaction between p97/VCP and FAF1, the p97/VCP N domain was
      crystallized in complex with the FAF1 UBX domain. X-ray data were collected to
      2.60 A resolution and the crystals belonged to space group C222(1), with unit
      cell parameters a = 58.24, b = 72.81, c = 132.93 A. The Matthews coefficient and
      solvent content were estimated to be 2.39 A(3) Da(-1) and 48.4%, respectively,
      assuming that the asymmetric unit contained p97/VCP N domain and FAF1 molecules
      in a 1:1 ratio, which was subsequently confirmed by molecular-replacement
      calculations.

PMID- 20057068
TI  - Crystallization and preliminary X-ray diffraction data of alpha-galactosidase
      from Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae alpha-galactosidase is a highly glycosylated
      extracellular protein that catalyzes the hydrolysis of alpha-galactosidic
      linkages in various glucids. Its enzymatic activity is of interest in many food
      related industries and has biotechnological applications. Glycosylated and in
      vitro deglycosylated protein samples were both assayed for crystallization, but
      only the latter gave good-quality crystals that were suitable for X-ray
      crystallography. The crystals belonged to space group P42(1)2, with unit-cell
      parameters a = b = 101.24, c = 111.52 A. A complete diffraction data set was
      collected to 1.95 A resolution using a synchrotron source.

PMID- 20057069
TI  - Crystallization and preliminary X-ray crystallographic analysis of DNA gyrase
      GyrB subunit from Xanthomonas oryzae pv. oryzae.
AB  - DNA gyrase is a type II topoisomerase that is essential for chromosome
      segregation and cell division owing to its ability to modify the topological
      forms of bacterial DNA. In this study, the N-terminal fragment of the GyrB
      subunit of DNA gyrase from Xanthomonas oryzae pv. oryzae was overexpressed in
      Escherichia coli, purified and crystallized. Diffraction data were collected to
      2.10 A resolution using a synchrotron-radiation source. The crystal belonged to
      space group I4(1), with unit-cell parameters a = b = 110.27, c = 70.75 A. The
      asymmetric unit contained one molecule, with a V(M) of 2.57 A(3) Da(-1) and a
      solvent content of 50.2%.

PMID- 20057070
TI  - Crystallization and preliminary X-ray diffraction data analysis of stenodactylin,
      a highly toxic type 2 ribosome-inactivating protein from Adenia stenodactyla.
AB  - Ribosome-inactivating proteins (RIPs) inhibit protein synthesis and induce cell
      death by removing a single adenine from a specific rRNA loop. They can be divided
      into two main groups: type 1 and type 2 RIPs. Type 1 RIPs are single-chain
      enzymes with N-glycosidase activity. Type 2 RIPs contain two chains (A and B)
      linked by a disulfide bond. The A chain has RIP enzymatic activity, whereas the B
      chain shows lectin activity and is able to bind to glycosylated receptors on the
      cell surface. Stenodactylin is a type 2 RIP from the caudex of Adenia
      stenodactyla from the Passifloraceae family that has been recently purified and
      characterized. It shows a strong enzymatic activity towards several substrates
      and is more cytotoxic than other toxins of the same type. Here, the
      crystallization and preliminary X-ray diffraction data analysis of stenodactylin
      are reported. This RIP forms crystals that diffract to high resolution (up to
      2.15 A). The best data set was obtained by merging data collected from two
      crystals. Stenodactylin crystals belonged to the centred monoclinic space group
      C2 and contained two molecules in the asymmetric unit.

PMID- 20057071
TI  - Crystallization and preliminary X-ray crystallographic analysis of Lon from
      Thermococcus onnurineus NA1.
AB  - Lon is an oligomeric ATP-dependent protease that degrades defective or denatured
      proteins as well as some folded proteins for the control of cellular protein
      quality and metabolism. Lon from Thermococcus onnurineus NA1 was purified and
      crystallized at 295 K. A 2.0 A resolution data set was collected using
      synchrotron radiation. The crystals belonged to space group P6(3), with unit-cell
      parameters a = 121.45, b = 121.45, c = 195.24 A. Assuming the presence of two
      monomers in the asymmetric unit, the solvent content was estimated to be about
      60.7%.

PMID- 20057072
TI  - Cloning, expression and crystallization of dihydrodipicolinate reductase from
      methicillin-resistant Staphylococcus aureus.
AB  - Dihydrodipicolinate reductase (DHDPR; EC 1.3.1.26) catalyzes the nucleotide
      (NADH/NADPH) dependent second step of the lysine-biosynthesis pathway in bacteria
      and plants. Here, the cloning, expression, purification, crystallization and
      preliminary X-ray diffraction analysis of DHDPR from methicillin-resistant
      Staphylococcus aureus (MRSA-DHDPR) are presented. The enzyme was crystallized in
      a number of forms, predominantly with ammonium sulfate as a precipitant, with the
      best crystal form diffracting to beyond 3.65 A resolution. Crystal structures of
      the apo form as well as of cofactor (NADPH) bound and inhibitor (2,6
      pyridinedicarboxylate) bound forms of MRSA-DHDPR will provide insight into the
      structure and function of this essential enzyme and valid drug target.

PMID- 20057073
TI  - Purification, crystallization and preliminary crystallographic studies of the
      complex of interferon-lambda1 with its receptor.
AB  - Human interferon-lambda1 (IFN-lambda1(Ins)) and the extracellular domain of
      interferon-lambda1 receptor (IFN-lambda1R1) were expressed in Drosophila S2 cells
      and purified to homogeneity. Both IFN-lambda1(Ins) and interferon-lambda1
      produced from Escherichia coli (IFN-lambda1(Bac)) were coupled with IFN-lambda1R1
      at room temperature and the complexes were purified by gel filtration. Both
      complexes were crystallized; the crystals were flash-frozen at 100 K and
      diffraction data were collected to 2.16 and 2.1 A, respectively. Although the IFN
      lambda1(Bac)-IFN-lambda1R1 and IFN-lambda1(Ins)-IFN-lambda1R1 complexes differed
      only in the nature of the expression system used for the ligand, their
      crystallization conditions and crystal forms were quite different. A search for
      heavy-atom derivatives as well as molecular-replacement trials are in progress.

PMID- 20057074
TI  - Crystallization and preliminary X-ray crystallographic analysis of Thermus
      thermophilus transcription elongation complex bound to Gfh1.
AB  - RNA polymerase (RNAP) elongates RNA by iterative nucleotide-addition cycles
      (NAC). A specific structural state (or states) of RNAP may be the target of
      transcription elongation factors. Gfh1, a Thermus thermophilus Gre-family
      protein, inhibits NAC. To elucidate which RNAP structural state Gfh1 associates
      with, the T. thermophilus RNAP elongation complex (EC) was cocrystallized with
      Gfh1. Of the 70 DNA/RNA scaffolds tested, two (for EC1 and EC2) were successfully
      crystallized. In the presence of Gfh1, EC1 and EC2 yielded crystals belonging to
      space group P2(1) with similar unit-cell parameters (crystals 1 and 2,
      respectively). X-ray diffraction data sets were obtained at 3.6 and 3.8 A
      resolution, respectively.

PMID- 20057075
TI  - Cloning, expression, purification, crystallization and preliminary
      crystallographic studies of UgdG, an UDP-glucose dehydrogenase from Sphingomonas
      elodea ATCC 31461.
AB  - Gellan gum, a commercial gelling agent produced by Sphingomonas elodea ATCC
      31461, is a high-value microbial exopolysaccharide. UDP-glucose dehydrogenase
      (UGD; EC 1.1.1.22) is responsible for the NAD-dependent twofold oxidation of UDP
      glucose to UDP-glucuronic acid, one of the key components for gellan
      biosynthesis. S. elodea ATCC 31461 UGD, termed UgdG, was cloned, expressed,
      purified and crystallized in native and SeMet-derivatized forms in hexagonal and
      tetragonal space groups, respectively; the crystals diffracted X-rays to 2.40 and
      3.40 A resolution, respectively. Experimental phases were obtained for the
      tetragonal SeMet-derivatized crystal form by a single-wavelength anomalous
      dispersion experiment. This structure was successfully used as a molecular
      replacement probe for the hexagonal crystal form of the native protein.

PMID- 20057076
TI  - Crystallization and preliminary X-ray crystallographic analysis of human PACSIN 1
      protein.
AB  - PACSIN 1, which is mainly detected in brain tissue, is one of the PACSIN-family
      proteins involved in endocytosis and recruitment of synaptic vesicles. It binds
      to dynamin, synaptojanin 1 and N-WASP, and functions in vesicle formation and
      transport. However, the mechanisms of action of PACSIN 1 in these processes are
      largely unknown. Here, full-length and five C-terminal truncation constructs of
      human PACSIN 1 have been successfully expressed and purified in Escherichia coli.
      PACSIN 1 (1-344) was crystallized and diffracted to a resolution of 3.0 A. The
      crystal belonged to space group C2, with unit-cell parameters a = 158.65, b =
      87.38, c = 91.76 A, alpha = 90.00, beta = 113.61, gamma = 90.00 degrees . There
      were two molecules in the asymmetric unit and the solvent content was estimated
      to be about 70.47%.

PMID- 20057077
TI  - Crystallization and preliminary X-ray diffraction analysis of the P3 RNA domain
      of yeast ribonuclease MRP in a complex with RNase P/MRP protein components Pop6
      and Pop7.
AB  - Eukaryotic ribonucleases P and MRP are closely related RNA-based enzymes which
      contain a catalytic RNA component and several protein subunits. The roles of the
      protein subunits in the structure and function of eukaryotic ribonucleases P and
      MRP are not clear. Crystals of a complex that included a circularly permuted 46
      nucleotide-long P3 domain of the RNA component of Saccharomyces cerevisiae
      ribonuclease MRP and selenomethionine derivatives of the shared ribonuclease
      P/MRP protein components Pop6 (18.2 kDa) and Pop7 (15.8 kDa) were obtained using
      the sitting-drop vapour-diffusion method. The crystals belonged to space group
      P4(2)22 (unit-cell parameters a = b = 127.2, c = 76.8 A, alpha = beta = gamma =
      90 degrees ) and diffracted to 3.25 A resolution.

PMID- 20057078
TI  - Purification, crystallization and preliminary X-ray analysis of Enterococcus
      casseliflavus aminoglycoside-2''-phosphotransferase-IVa.
AB  - The deactivation of aminoglycoside antibiotics by chemical modification is one of
      the major sources of bacterial resistance to this family of therapeutic
      compounds, which includes the clinically relevant drugs streptomycin, kanamycin
      and gentamicin. The aminoglycoside phosphotransferases (APHs) form one such
      family of enzymes responsible for this resistance. The gene encoding one of these
      enzymes, aminoglycoside-2''-phosphotransferase-IVa [APH(2'')-IVa] from
      Enterococcus casseliflavus, has been cloned and the protein (comprising 306 amino
      acid residues) has been expressed in Escherichia coli and purified. The enzyme
      was crystallized in three substrate-free forms. Two of the crystal forms belonged
      to the orthorhombic space group P2(1)2(1)2(1) with similar unit-cell parameters,
      although one of the crystal forms had a unit-cell volume that was approximately
      13% smaller than the other and a very low solvent content of around 38%. The
      third crystal form belonged to the monoclinic space group P2(1) and preliminary X
      ray diffraction analysis was consistent with the presence of two molecules in the
      asymmetric unit. The orthorhombic crystal forms of apo APH(2'')-IVa both
      diffracted to 2.2 A resolution and the monoclinic crystal form diffracted to 2.4
      A resolution; synchrotron diffraction data were collected from these crystals at
      SSRL (Stanford, California, USA). Structure determination by molecular
      replacement using the structure of the related enzyme APH(2'')-IIa is proceeding.

PMID- 20057079
TI  - Towards structural studies of the old yellow enzyme homologue SYE4 from
      Shewanella oneidensis and its complexes at atomic resolution.
AB  - Shewanella oneidensis is an environmentally versatile Gram-negative gamma
      proteobacterium that is endowed with an unusually large proteome of redox
      proteins. Of the four old yellow enzyme (OYE) homologues found in S. oneidensis,
      SYE4 is the homologue most implicated in resistance to oxidative stress. SYE4 was
      recombinantly expressed in Escherichia coli, purified and crystallized using the
      hanging-drop vapour-diffusion method. The crystals belonged to the orthorhombic
      space group P2(1)2(1)2(1) and were moderately pseudo-merohedrally twinned,
      emulating a P422 metric symmetry. The native crystals of SYE4 were of exceptional
      diffraction quality and provided complete data to 1.10 A resolution using
      synchrotron radiation, while crystals of the reduced enzyme and of the enzyme in
      complex with a wide range of ligands typically led to high-quality complete data
      sets to 1.30-1.60 A resolution, thus providing a rare opportunity to dissect the
      structure-function relationships of a good-sized enzyme (40 kDa) at true atomic
      resolution. Here, the attainment of a number of experimental milestones in the
      crystallographic studies of SYE4 and its complexes are reported, including
      isolation of the elusive hydride-Meisenheimer complex.

PMID- 20057080
TI  - Crystallization and preliminary crystallographic analysis of the measles virus
      hemagglutinin in complex with the CD46 receptor.
AB  - The measles virus (MV) hemagglutinin (MV-H) mediates the attachment of MV
      particles to cell-surface receptors for entry into host cells. MV uses two
      receptors for attachment to host cells: the complement-control protein CD46 and
      the signalling lymphocyte activation molecule (SLAM). The MV-H glycoprotein from
      an Edmonston MV variant and the MV-binding fragment of the CD46 receptor were
      overproduced in mammalian cells and used to crystallize an MV-H-CD46 complex.
      Well diffracting crystals containing two complexes in the asymmetric unit were
      obtained and the structure of the complex was solved by the molecular-replacement
      method.

PMID- 20057081
TI  - Crystallization and preliminary X-ray characterization of the Skp1-Fbg3 complex.
AB  - F-box proteins are the substrate-recognition components of Skp1-Cullin1-F-box
      protein-Rbx1 (SCF) ubiquitin ligase complexes. Fbs1, an F-box protein, binds
      specifically to proteins modified with high-mannose oligosaccharides. Fbg3,
      another F-box protein, has 51% sequence identity to Fbs1. Although the residues
      that are necessary for binding to oligosaccharides are conserved between Fbs1 and
      Fbg3, Fbg3 does not bind glycoproteins. Skp1 and Fbg3 were co-expressed in
      Escherichia coli and their complex was purified to homogeneity and crystallized.
      Microseeding combined with the sandwiched hanging-drop technique improved the
      quality of the resulting crystals. The plate-shaped crystals belonged to space
      group P2(1)2(1)2(1), with unit-cell parameters a = 34.1, b = 76.6, c = 193.9 A
      and one molecule per asymmetric unit.

PMID- 20057082
TI  - Complex assembly, crystallization and preliminary X-ray crystallographic studies
      of duck MHC class I molecule.
AB  - In order to understand the biological properties of the immune systems of
      waterfowl and to establish a system for structural studies of duck class I major
      histocompatibility complex (DuMHC I), a complex of DuMHC I with duck beta(2)
      microglobulin (Dubeta(2)m) and the peptide AEIEDLIF (AF8) derived from H5N1 NP
      residues 251-258 was assembled. The complex was crystallized; the crystals
      belonged to space group C222(1), with unit-cell parameters a = 54.7, b = 72.4, c
      = 102.2 A, and diffracted to 2.3 A resolution. Matthews coefficient calculation
      and initial structure determination by molecular replacement showed that the
      crystals did not contain the whole DuMHC I complex, but instead contained the
      DuMHC I alpha3 domain and a Dubeta2m molecule (DuMHC I alpha3+beta2m). Another
      complex of DuMHC I with the peptide IDWFDGKE derived from a chicken fusion
      protein also generated the same results. The stable structure of DuMHC I
      alpha3+beta2m may reflect some unique characteristics of DuMHC I and pave the way
      for novel MHC structure-related studies in the future.

PMID- 20057083
TI  - Crystallization and preliminary X-ray diffraction analysis of inositol 1,3,4,5,6
      pentakisphosphate kinase from Arabidopsis thaliana.
AB  - Inositol 1,3,4,5,6-pentakisphosphate kinase (IP(5) 2-K) is an enzyme involved in
      inositol metabolism that synthesizes IP(6) (inositol 1,2,3,4,5,6
      hexakisphosphate) from inositol 1,3,4,5,6-pentakisphosphate (IP(5)) and ATP.
      IP(6) is the major phosphorus reserve in plants, while in mammals it is involved
      in multiple cellular events such as DNA editing and chromatin remodelling. In
      addition, IP(6) is the precursor of other highly phosphorylated inositols which
      also play highly relevant roles. IP(5) 2-K is the only enzyme that phosphorylates
      the 2-OH axial position of the inositide and understanding its molecular
      mechanism of substrate specificity is of great interest in cell biology. IP(5) 2
      K from Arabidopsis thaliana has been expressed in Escherichia coli as two
      different fusion proteins and purified. Both protein preparations yielded
      crystals of different quality, always in the presence of IP(6). The best crystals
      obtained for X-ray crystallographic analysis belonged to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 58.124, b = 113.591, c = 142.478 A.
      Several diffraction data sets were collected for the native enzyme and two heavy
      atom derivatives using a synchrotron source.

PMID- 20057085
TI  - Application of mitochondrial DNA analysis for microbial source tracking purposes
      in shellfish harvesting waters.
AB  - We present a method for the reliable detection and source characterisation of
      faecal pollution in water and shellfish matrices, utilising real-time PCR
      analysis of mitochondrial DNA targets. In this study we designed real-time PCR
      (TaqMan) probes to target human, bovine, ovine and swine mtDNA. PCR amplification
      using species-specific TaqMan probes on faecal matter and mixed effluent slurries
      revealed no cross-reactions between species of interest and other vertebrate
      faecal matter. Performed as a single blind experiment we were able to correctly
      identify faecal material in 17/20 effluents (85% correct). mtDNA degrades
      relatively quickly in faecally-spiked water samples (approximately 2 weeks), a
      similar timeframe of environmental persistence to several bacterial faecal
      indictors, highlighting its applicability. The procedure described here is
      specific, rapid (<5 hours) and sensitive. These results confirm the suitability
      of using species-specific mtDNA as an indicator in source tracking studies in
      surface waters, shellfish harvesting areas and shellfish matrices.

PMID- 20057086
TI  - Molecular analysis of the bacterial drinking water community with respect to
      live/dead status.
AB  - The assessment of the physiological state of the bacteria in drinking water is a
      critical issue, especially with respect to the presence of pathogenic bacteria.
      Though molecular methods can provide insight into the taxonomic composition of
      the drinking water microflora, the question if a bacterial species is alive or
      dead still needs to be addressed. To distinguish live and dead bacteria at the
      taxonomic level, we combined three methods: i) a staining procedure indicating
      membrane-injured cells (using SYTO9 and Propidium Iodide) that is considered to
      distinguish between live and dead cells, ii) Fluorescence Activated Cell Sorting
      (FACS) of the membrane injured and intact bacteria, and iii) molecular analyses
      of the RNA extracted from the bacteria before and after sorting to analyse the
      bacterial community at the species level. By staining and FACS analysis the
      drinking water bacteria could be separated according to their different membrane
      integrities, and RNA could be extracted from the live and dead sorted bacterial
      fractions. 16S rRNA based fingerprints revealed a diverse bacterial community in
      the drinking water samples with the majority being represented by 31 identified
      phylotypes. Most of the phylotypes referenced belonged to the phyla
      Proteobacteria (Alpha-, Beta-, Gamma-), Cyanobacteria and Bacteroidetes, and were
      mostly related to freshwater bacteria. 90% of the total phylotypes could be
      recovered after FAC-Sorting; 32% of the phylotypes occurred only in the "live"
      sorted fraction, 21% only in the "dead" sorted fraction, and 46% occurred in both
      fractions.

PMID- 20057087
TI  - Genotyping of hepatitis A virus detected in bivalve shellfish in Galicia (NW
      Spain).
AB  - Hepatitis A virus (HAV) represents a significant public health problem due to its
      high persistence in the environment and its transmission through contaminated
      water and food. Bivalve shellfish are filter feeders that can bioaccumulate human
      pathogens found in contaminated waters, their consumption being a potential cause
      of hepatitis A outbreaks. In this work, cultured and wild bivalve shellfish from
      the Ria de Vigo (Galicia, NW Spain) were analysed for the presence and genotyping
      of HAV. A total of 160 shellfish samples were collected between March 2004 and
      December 2006, including 68 samples from cultured mussels (Mytilus
      galloprovincialis), 30 from wild clams (Rupitapes decussatus), 31 from wild
      cockles (Cerastoderma edule) and 31 from wild mussel. HAV detection, carried out
      by quantitative RT-PCR, was positive for 29 (42.6%) cultured and 40 (43.5%) wild
      samples, with levels ranging from 3.1 x 10(2) and 1.4 x 10(10) RNA copies/g of
      shellfish digestive tissue. The phylogenetic analysis of VP1-P2A and VP3-VP1
      regions, separately or as concatenated sequences, revealed that all HAV strains
      analysed belong to subgenotype IB. These results indicate a high prevalence of
      this subgenotype in the area studied.

PMID- 20057088
TI  - Investigating the influences of season and coastal proximity on the elemental
      composition of harvested rainwater.
AB  - Chemical qualities of harvested rainwater were assessed at two residential study
      sites on the east coast of Australia in relation to coastal proximity and
      surrounding land uses over the course of a winter and summer month. Daily
      rainwater samples were collected from the base outlet and surface levels of
      stored water for chemical analyses. High resolution inductively coupled plasma
      mass spectrometry (ICP-MS) was used to analyse 26 elements in all samples. The
      summer sampling regime for the industrial coastal Site 1 was dominated by wind
      gusts originating from the east with a total average elemental load of 25,900+/
      17,000 microg/L compared to the significantly lower 10,600+/-3,370 microg/L
      measured during the winter month, where 84% of wind gust events originated from
      the west. Data for the inland Site 2, with no proximity to industry, revealed no
      significant changes in total average loads between the winter (4,870+/-578
      microg/L) and summer (4,760+/-2,280 microg/L) months. The most abundant elements
      found at both sites included Na, K, Mg, and Zn. The rainwater storages at Site 2
      fed from a relatively new concrete tiled roof catchment had significantly lower
      pH and conductivity measurements compared with those at Site 1 with an old
      galvanised iron roof catchment. It was concluded that seasonal differences in
      harvested water quality were likely influenced by prevailing wind direction and
      external influences such as surrounding land uses and proximity to the coast.

PMID- 20057089
TI  - A multi-layer cellular automata approach for algorithmic generation of virtual
      case studies: VIBe.
AB  - Analyses of case studies are used to evaluate new or existing technologies,
      measures or strategies with regard to their impact on the overall process.
      However, data availability is limited and hence, new technologies, measures or
      strategies can only be tested on a limited number of case studies. Owing to the
      specific boundary conditions and system properties of each single case study,
      results can hardly be generalized or transferred to other boundary conditions.
      virtual infrastructure benchmarking (VIBe) is a software tool which
      algorithmically generates virtual case studies (VCSs) for urban water systems.
      System descriptions needed for evaluation are extracted from VIBe whose
      parameters are based on real world case studies and literature. As a result VIBe
      writes Input files for water simulation software as EPANET and EPA SWMM. With
      such input files numerous simulations can be performed and the results can be
      benchmarked and analysed stochastically at a city scale. In this work the
      approach of VIBe is applied with parameters according to a section of the Inn
      valley and therewith 1,000 VCSs are generated and evaluated. A comparison of the
      VCSs with data of real world case studies shows that the real world case studies
      fit within the parameter ranges of the VCSs. Consequently, VIBe tackles the
      problem of limited availability of case study data.

PMID- 20057090
TI  - The SHARON process in the treatment of landfill leachate.
AB  - The purpose of this paper was to study the partial nitrification of the nitrogen
      present in a landfill leachate applying the SHARON process in order to obtain a
      suitable effluent to the ANAMMOX process. As a first step, the SHARON reactor was
      fed anaerobically pre-treated leachate at an ammonium concentration of 2,000 mg
      N/L (1.1 kg N/m(3) d). In such conditions, the average ammonium and nitrite
      concentrations in the effluent were 775 mg N/L and 1,225 mg N/L, respectively.
      During this period the COD removal was very low since most of the biodegradable
      organic matter was removed in the anaerobic pre-treatment. Afterwards, the SHARON
      reactor was fed leachate without a previous treatment and the efficiency of the
      partial nitritation diminished. As well, the COD removal increased, achieving a
      percentage around 28%.

PMID- 20057091
TI  - Evolutionary parameter optimization of a fuzzy controller which is used to
      control a sewage treatment plant.
AB  - In order to meet new environmental standards, sewage treatment plants may need to
      be redesigned or extended. Instead of reconstructing large parts of a sewage
      treatment plant, which can be very costly, it is in many cases sufficient to
      install relatively inexpensive equipment, which controls parts of the plant in a
      new way. Fuzzy controllers are often used for this task. Use of these controllers
      often leads to an improved water quality. Such fuzzy controllers contain a number
      of parameters which are determined by a human expert. With this contribution, a
      dedicated multi-objective evolutionary algorithm is developed to optimize these
      parameters. The evolutionary algorithm is based on the successful strength pareto
      evolutionary algorithm 2 (SPEA2). The fuzzy control parameters, which are
      optimized are continuous parameters. Therefore, an evolution strategy was
      employed which uses the multi-objective ranking as used by the SPEA2 algorithm.
      Optimal parameters were first evolved on simulated sewage treatment plants. One
      set of parameters was also tested on an actual plant. Owing to the enormous
      computational demands of simulating a sewage treatment plant, it is only possible
      to work with small population sizes. Nevertheless, it was possible to evolve
      parameters which were equally well as those found by a human expert indicating
      that the parameter tuning can be automized.

PMID- 20057092
TI  - Equivalency testing of TTC Tergitol 7 agar (ISO 9308-1:2000) with five culture
      media for the detection of E. coli in water samples in Greece.
AB  - In this study ten laboratories in Greece compared the performance of reference
      method TTC Tergitol 7 Agar (with the additional test of beta-glucuronidase
      production) with five alternative methods, to detect E. coli in water, in line
      with European Water Directive recommendations. The samples were prepared by
      spiking drinking water with sewage effluent following a standard protocol.
      Chlorinated and non-chlorinated samples were used. The statistical analysis was
      based on the mean relative difference of confirmed counts and was performed in
      line with ISO 17994. The results showed that in total, three of the alternative
      methods (Chromocult Coliform agar, Membrane Lauryl Sulfate agar and Trypton Bilex
      glucuronidase medium) were not different from TTC Tergitol 7 agar (TTC Tergitol 7
      agar vs Chromocult Coliform agar, 294 samples, mean RD% 5.55; vs MLSA, 302
      samples, mean RD% 1; vs TBX, 297 samples, mean RD% -2.78). The other two
      alternative methods (Membrane Faecal coliform medium and Colilert 18/ Quantitray)
      gave significantly higher counts than TTC Tergitol 7 agar (TTC Tergitol 7 agar vs
      MFc, 303 samples, mean RD% 8.81; vs Colilert-18/Quantitray, 76 samples, mean RD%
      18.91). In other words, the alternative methods generated performance that was as
      reliable as, or even better than, the reference method. This study will help
      laboratories in Greece overcome culture and counting problems deriving from the
      EU reference method for E. coli counts in water samples.

PMID- 20057093
TI  - Quantifying human exposure to contaminants for multiple-barrier water reuse
      systems.
AB  - Reliance upon advanced water treatment processes to provide safe drinking water
      from relatively compromised sources is rapidly increasing in Australia and other
      parts of the world. Advanced treatment processes such as reverse osmosis have the
      ability to provide very effective treatment for a wide range of chemicals when
      operated under optimal conditions. However, techniques are required to
      comprehensively validate the performance of these treatment processes in the
      field. This paper provides a discussion and demonstration of some effective
      statistical techniques for the assessment and description of advanced water
      treatment plant performance. New data is provided, focusing on disinfection
      byproducts including trihalomethanes and N-nitrosamines from a recent
      comprehensive quantitative exposure assessment for an advanced water recycling
      scheme in Australia.

PMID- 20057094
TI  - Rainwater harvesting: model-based design evaluation.
AB  - The rate of uptake of rainwater harvesting (RWH) in the UK has been slow to date,
      but is expected to gain momentum in the near future. The designs of two different
      new-build rainwater harvesting systems, based on simple methods, are evaluated
      using three different design methods, including a continuous simulation modelling
      approach. The RWH systems are shown to fulfill 36% and 46% of WC demand.
      Financial analyses reveal that RWH systems within large commercial buildings
      maybe more financially viable than smaller domestic systems. It is identified
      that design methods based on simple approaches generate tank sizes substantially
      larger than the continuous simulation. Comparison of the actual tank sizes and
      those calculated using continuous simulation established that the tanks installed
      are oversized for their associated demand level and catchment size. Oversizing
      tanks can lead to excessive system capital costs, which currently hinders the
      uptake of systems. Furthermore, it is demonstrated that the catchment area size
      is often overlooked when designing UK-based RWH systems. With respect to these
      findings, a recommendation for a transition from the use of simple tools to
      continuous simulation models is made.

PMID- 20057095
TI  - Treatment of segregated black/grey domestic wastewater using constructed wetlands
      in the Mediterranean basin: the zer0-m experience.
AB  - Concerns about water shortage and pollution have received increased attention
      over the past few years, especially in developing countries with warm climate. In
      order to help local water management in these countries, the Euro-Mediterranean
      Regional Programme (MEDA) has financed the Zer0-m project (E-mail: www.zer0
      m.org). As a part of this project, several constructed wetland (CW) pilot systems
      with different pre-treatments have been implemented in four Technological
      Demonstration Centres in Egypt, Morocco, Tunisia and Turkey. The aim of this
      research was to establish appropriate designs for treatment of segregated
      domestic black (BW) and grey water (GW). We tested several different multistage
      CW configurations, consisting of horizontal and vertical subsurface flow CW for
      secondary treatment and free water systems as tertiary stage. CW removal
      efficiencies of TSS, COD, BOD(5), N-NH(4)(+), N-NO(3)(-), N(tot), total coliforms
      (TC) were evaluated for each of the implemented systems. The results from this
      study demonstrate the potential of CWs as a suitable technology for treating
      segregated domestic wastewater. A very efficient COD reduction (up to 98%) and
      nitrification (92-99%) was achieved for BW and GW in all systems. CW effluent
      concentrations were below 15 mg/L for BOD(5), 1 mg/L for N-NO(3)(-) and 0.5 mg/L
      for N-NH(4)(+) together with acceptable TC counts. Based on these results, we
      suggest adopting the design parameters used in this study for the treatment of
      segregated wastewater in the Mediterranean area.

PMID- 20057096
TI  - Killing of Escherichia coli using the gas diffusion electrode system.
AB  - To be best of our knowledge, this study is one of the first investigations to be
      performed into the potential benefits of gas diffusion electrode (GDE) system in
      controlling inactivation of E. coli. This study mainly focused on the dual
      electrodes disinfection with gas diffusion cathode, using Escherichia coli as the
      indicator microorganisms. The effects of Pt load W(Pt) and the pore-forming agent
      content W(NH(4)HCO(3)) in GDE, operating conditions such as pH value, oxygen flow
      rate Q(O(2)), salt content and current density on the disinfection were
      investigated, respectively. The experimental results showed that the disinfection
      improved with increasing Pt load W(Pt), but its efficiency at Pt load of 3 per
      thousand was equivalent to that at Pt load of 4 per thousand. Addition of the
      pore-forming agent in the appropriate amount improved the disinfection while drop
      of pH value resulted in the rapid rise of the germicidal efficacy and the
      disinfection shortened with increasing oxygen flow rate Q(O(2)). The system is
      more suitable for highly salt water. The germicidal efficacy increased with
      current density. However, the accelerating rate was different: it first increased
      with the current density, then decreased, and reached a maximum at current
      density of 6.7-8.3 mA/cm(2). The germicidal efficacy in the cathode compartment
      was about the same as in the anode compartment indicating the contribution of
      direct oxidation and indirect treatment of E. coli by the hydroxyl radical was
      similar to the oxidative indirect effect of the generated H(2)O(2). This
      technology is expensive in operating cost, further research is required to
      advance the understanding and reduce the operating cost of this technology.

PMID- 20057097
TI  - Enrichment of marine anammox bacteria from seawater-related samples and bacterial
      community study.
AB  - Anaerobic ammonium oxidation (anammox) is a novel nitrogen pathway catalyzed by
      anammox bacteria which are obligate anaerobic chemoautotrophs. In this study,
      enrichment culture of marine anammox bacteria (MAAOB) from the samples related to
      seawater was conducted. Simultaneous removal of ammonium and nitrite was
      confirmed in continuous culture inoculated with sediment of a sea-based waste
      disposal site within 50 days. However, no simultaneous nitrogen removal was
      observed in cultures inoculated with seawater-acclimated denitrifying sludge or
      with muddy sediment of tideland even during 200 days. Nitrogen removal rate of
      0.13 kg/m(3)/day was achieved at nitrogen loading rate of 0.16 kg/m(3)/day after
      320th days in the culture inoculated with the sediment of waste disposal site.
      The nitrogen removal ratio between ammonium nitrogen and nitrite nitrogen was
      1:1.07. Denaturing gradient gel electrophoresis (DGGE) analysis indicated that an
      abundance of the bacteria close to MAAOB and coexistence of ammonium oxidizing
      bacteria and denitrifying bacteria in the culture.

PMID- 20057098
TI  - Stability of metal oxide nanoparticles in aqueous solutions.
AB  - The application of nanoparticles in the processes of making commercial products
      has increased in recent years due to their unique physical and chemical
      properties. With increasing amount of commercial nanoparticles released into
      nature, their fate and effects on the ecosystem and human health are of growing
      concern. This study investigated the stability and morphology of three metal
      oxide nanoparticles in aqueous solutions. The commercially available
      nanoparticles, TiO(2), ZnO, SiO(2), aggregated quickly into micrometer-size
      particles in aqueous solutions, which may not threaten human health. Their
      changes in morphology and characteristics were further examined by dynamic light
      scattering (DLS) method and transmission electron microscopy (TEM). Among the
      several dispersion approaches, ultrasonication was found to be the most effective
      for disaggregating nanoparticles in water. For these three selected
      nanoparticles, ZnO could not remain stable in suspensions, presumably due to the
      dissolution of particles to form high concentration of ions, resulting in
      enhanced aggregation of particles. In addition, the existence of dissolved
      organic matters stabilized nanoparticles in lake water and wastewater for several
      hours in spite of the high concentration of cations in these real-water samples.
      The fate of metal oxide nanoparticles in natural water bodies would be determined
      by the type and concentration of cations and organic matters. Results obtained in
      this study revealed that the stability of nanoparticles changed under different
      aqueous conditions and so did their fate in the environment.

PMID- 20057099
TI  - Management of combined sewer overflows based on observations from the urbanized
      Liguori catchment of Cosenza, Italy.
AB  - This paper examines an urbanized catchment in Cosenza, Italy where an off-line
      basin intercepting CSOs was studied to illustrate reduction in CSO discharges to
      the Crati River. While the hydrologic transport of pollutant mass is never known
      a-priori and can be flow-limited, the volumetric requirements of the basin were
      modeled based on the classic assumption that wet weather flows transport urban
      and sewer loads in a mass-limited (first-flush) delivery. The volumetric capacity
      of the basin was varied from 10 to 50 m(3)/ha. Operational basin control was
      simulated with historical datasets from the Liguori catchment, event-based
      loading data, and continuous simulation modelling with SWMM. Utilizing data from
      the catchment, the SWMM simulations were conducted considering the storage basin
      with or without sedimentation treatment. Results illustrate the potential
      benefits of the off-line operation for the system with respect to the volume and
      mass reduction of CSOs into the Crati River. Results demonstrate the importance
      of particle size distribution (PSD) as an index of basin efficiency, coupled with
      analysis of the hydrodynamic response of the basin. The basin model attenuated
      influent PSDs, separating the coarser fraction of the PSD, and reduced the load
      of influent particulate matter (PM).

PMID- 20057100
TI  - Endocrine disruptors and pharmaceuticals: implications for water sustainability.
AB  - The presence of pharmaceuticals and endocrine disrupting compounds (EDCs) in the
      environment raises many questions about risk to the environment and risk to human
      health. Researchers have attributed adverse ecological effect effects to the
      presence of these compounds, particularly EDCs, though there is no consensus on
      what risk, if any, these compounds pose to human health. The scientific community
      is in the process of developing a better understanding of the occurrence, fate,
      and transport of pharmaceuticals and EDCs in the environment, including a better
      characterization of human exposure via drinking water. This paper provides a
      brief review of pharmaceuticals and EDCs in drinking water, as well as uses
      examples from Lake Mead, Nevada, USA, to highlight the issues associated with
      their fate and transport. Lastly, the effects of natural or anthropogenically
      driven processes, like natural seasonal flow or climate-change/prolonged drought
      are discussed as they are factors which can drastically alter environmental
      concentrations of these compounds. Without question, the propensity for the
      contamination of fresh water will rise as (1) human population continues to grow
      or (2) patterns of natural surface water slow and wastewater becomes a larger
      fraction of flow further highlighting the need for a more comprehensive
      understanding of their environmental behavior.

PMID- 20057101
TI  - Fluorescence monitoring for cross-connection detection in water reuse systems:
      Australian case studies.
AB  - A rapid, highly sensitive method for detection of cross-connections between
      recycled and potable water in dual reticulation systems is required. The aim of
      this research was to determine the potential of fluorescence spectroscopy as a
      monitoring tool at three Australian dual distribution (drinking and recycled
      water) systems. Weekly grab samples of recycled and potable water were obtained
      over 12 weeks at each site and analysed for fluorescence excitation-emission
      matrix (EEM) spectroscopy, UV(254), dissolved organic carbon (DOC), electrical
      conductivity and pH. Fluorescence EEM spectroscopy was able to differentiate
      between recycled and potable water at each site by monitoring the protein-like
      fluorescence at peak T-an excitation-emission wavelength pair of lambda(ex/em) =
      300/350 nm. While electrical conductivity was also able to distinguish between
      recycled and potable water, the differentiation was greatest when using
      fluorescence. For example, the peak T fluorescence in recycled water was up to 10
      times that of potable water in comparison with electrical conductivity that had a
      maximum 5 times differentiation. Furthermore, by comparing the protein-like
      fluorescence at peak T and humic-like fluorescence at peak A (lambda(ex/em) =
      235/426 nm), the three different recycled water systems were able to be
      differentiated. Overall, fluorescence shows promise as a monitoring tool for
      detecting cross-connections.

PMID- 20057103
TI  - The World Health Organization's water safety plan is much more than just an
      integrated drinking water quality management plan.
AB  - South Africa is a country of contrasts with far ranging variations in climate,
      precipitation rates, cultures, demographics, housing levels, education, wealth
      and skills levels. These differences have an impact on water services delivery as
      do expectations, affordability and available resources. Although South Africa has
      made much progress in supplying drinking water, the same cannot be said regarding
      water quality throughout the country. A concerted effort is currently underway to
      correct this situation and as part of this drive, water safety plans (WSP) are
      promoted. Rand Water, the largest water services provider in South Africa, used
      the World Health Organization (WHO) WSP framework as a guide for the development
      of its own WSP which was implemented in 2003. Through the process of
      implementation, Rand Water found the WHO WSP to be much more than just another
      integrated quality system.

PMID- 20057102
TI  - Microbial diversity in biofilms on water distribution pipes of different
      materials.
AB  - The effects of pipe materials on biofilm formation potential (BFP) and microbial
      communities in biofilms were analyzed. Pipe coupons made of six different
      materials (CU, copper; CP, chlorinated poly vinyl chloride; PB, polybutylene; PE,
      polyethylene; SS, stainless steel; ST, steel coated with zinc) were incubated in
      drinking water, mixed water (inoculated with 10% (v/v) of river water) and
      drinking water inoculated with Escherichia coli JM109 (E. coli), respectively.
      The highest BFPs were observed from steel pipes, SS and ST, while CU showed the
      lowest BFP values. Of the plastic materials, the BFP of CP in drinking water (96
      pg ATP/cm(2)) and mixed water (183 pg ATP/cm(2)) were comparable to those of CU,
      but the other plastic materials, PB and PE, displayed relatively high BFP. The
      Number of E. coli in the drinking water inoculated with cultures of E. coli
      strain showed similar trends with BFP values of the pipe coupons incubated in
      drinking water and mixed water. Molecular analysis of microbial communities
      indicated the presence of alpha- and beta-proteobacteria, actinobacteria and
      bacteroidetes in biofilm on the pipe materials. However, the DGGE profile of
      bacterial 16S rDNA fragments showed significant differences among different
      materials, suggesting that the pipe materials affect not only BFP but also
      microbial diversity. Some plastic materials, such as CP, would be suitable for
      plumbing, particularly for drinking water distribution pipes, due to its low BFP
      and little microbial diversity in biofilm.

PMID- 20057104
TI  - Advanced water recycling through electrochemical treatment of effluent from
      dissolved air flotation unit of food processing industry.
AB  - This study elucidates the feasibility of electrochemical treatment as a water
      recycling process in the dissolved air flotation (DAF) unit in the food industry.
      Effects of operation parameters such as current density, electrolysis time,
      initial pH of effluent, and mixing process were investigated on the removal of
      COD, TSS, and TDS of the DAF pretreated effluent. An increase of current density
      enhances the removal rates and reduces the electrolysis time to reach the maximum
      performance. The initial pH less than 7 and the addition of mixing process were
      proven to increase the efficiency of EC treatment. About 80% of COD, 100% of TSS,
      and 60% of TDS were successfully removed at 500 mA current for 1 hour of
      electrolysis. The final treated effluent was found to meet the discharge standard
      from the US Environmental Protection Agency. It was concluded that EC process
      could be effective as an advanced water resourcing technology in the food
      industry.

PMID- 20057105
TI  - Occurrence and fate of benzothiazoles and benzotriazoles in constructed wetlands.
AB  - A suite of benzothiazoles and benzotriazoles was analysed by comprehensive multi
      dimensional gas chromatography coupled to time-of-flight mass spectrometry in
      four different wastewater treatment systems. The selected wastewater treatment
      systems include one conventional wastewater treatment plant (WWTP) and for the
      first time, two constructed wetlands. Although benzothiazole (BT), 2
      (methylthio)benzothiazole (MTBT), 2-hydroxybenzothiazole (OHBT) and benzotriazole
      (BTri) occurred in all the raw wastewater samples, 4- and 5-methylbenzotriazoles
      (4- and 5-TTri) were only detected in the industrially impacted wastewater.
      Concentrations of benzothiazoles and benzotriazoles in raw wastewater ranged from
      0.2 to 2.2 microg L(-1) and from 0.06 to 36.2 microg L(-1), respectively. The
      benzothiazoles removal efficiencies ranged from zero to up to 80% in the
      conventional WWTP and from 83 to 90% in constructed wetlands. For BTri, removal
      efficiencies ranged from 65 to 70% and from 89 to 93% in conventional WWTP and
      constructed wetlands, respectively. The higher performance of CWs in the removal
      of these compounds might be attributed to the contribution of biodegradation,
      photodegradation and plant uptake.

PMID- 20057106
TI  - Toxicity and recalcitrant compound removal from bleaching pulp plant effluents by
      an integrated system: anaerobic packed-bed bioreactor and ozone.
AB  - Effluents originated in cellulose pulp manufacturing processes are usually toxic
      and recalcitrant, specially the bleaching effluents, which exhibit high contents
      of aromatic compounds (e.g. residual lignin derivates). Although biological
      processes are normally used, their efficiency for the removal of toxic lignin
      derivates is low. The toxicity and recalcitrance of a bleached Kraft pulp mill
      were assessed through bioassays and ultraviolet absorption measurements, i.e.
      acid soluble lignin (ASL), UV(280), and specific ultraviolet absorption (SUVA),
      before and after treatment by an integrated system comprised of an anaerobic
      packed-bed bioreactor and oxidation step with ozone. Furthermore, adsorbable
      organic halides (AOX) were measured. The results demonstrated not only that the
      toxic recalcitrant compounds can be removed successfully using integrated system,
      but also the ultraviolet absorption measurements can be an interesting control
      parameter in a wastewater treatment.

PMID- 20057107
TI  - Toxicity and pollutant impact analysis in an urban river due to combined sewer
      overflows loads.
AB  - The Navile Channel (Bologna, Italy) is an ancient artificial water course derived
      from the Reno river. It is the main receiving water body for the urban catchment
      of Bologna sewer systems and also for the Waste Water Treatment Plant (WWTP) main
      outlet. The aim of this work is to evaluate the Combined Sewer Overflows (CSOs)
      impact on Navile Channel's water quality. In order to collect Navile flow and
      water quality data in both dry and wet weather conditions, two measuring and
      sampling stations were installed, right upstream and downstream the WWTP outflow.
      The study shows that even in case of low intensity rain events, CSOs have a
      significant effect on both water quantity and quality, spilling a considerable
      amount of pollutants into the Navile Channel and presenting also acute toxicity
      effects. The collected data shown a good correlations between the concentrations
      of TSS and of chemical compounds analyzed, suggesting that the most part of such
      substances is attached to suspended solids. Resulting toxicity values are fairly
      high in both measuring points and seem to confirm synergistic interactions
      between heavy metals.

PMID- 20057108
TI  - One-year operation of single household membrane bioreactor plant.
AB  - This paper evaluates the results from a 12-month study of a single-household
      wastewater treatment plant with submerged membrane module (household MBR plant)
      that was monitored from winter to winter season. The samples were collected at
      least twice a week (an intensive research study at real conditions). The
      household MBR (membrane bioreactor) plant was linked to a family house with 4
      residents. In this study the treatment plant was fed by real domestic wastewater.
      In contrast to most other experiments with small-scale WWTPs (wastewater
      treatment plants) carried out in laboratories and facilities of large municipal
      WWTPs (polygons) which guarantee stable and flexible operation but the
      characteristics of wastewater and activated sludge in these studies usually
      differ from those that occur in real small-scale/single-household WWTPs. One of
      the main goals of this research was to test the response of membrane and
      activated sludge to different conditions during real operation of the household
      MBR plant, such as a long period of zero influent/load, or vice versa the
      presence of a large amount of concentrated wastewater (e.g. during the weekend),
      very low winter temperatures (water temperature below 5-6 degrees C), high pH
      values, and the presence of domestic detergents.

PMID- 20057109
TI  - Integration between chemical oxidation and membrane thermophilic biological
      process.
AB  - Full scale applications of activated sludge thermophilic aerobic process for
      treatment of liquid wastes are rare. This experimental work was carried out at a
      facility, where a thermophilic reactor (1,000 m(3) volume) is operated. In order
      to improve the global performance of the plant, it was decided to upgrade it, by
      means of two membrane filtration units (ultrafiltration -UF-, in place of the
      final sedimentation, and nanofiltration -NF-). Subsequently, the integration with
      chemical oxidation (O(3) and H(2)O(2)/UV processes) was taken into consideration.
      Studied solutions dealt with oxidation of both the NF effluents (permeate and
      concentrate). Based on experimental results and economic evaluation, an algorithm
      was proposed for defining limits of convenience of this process.

PMID- 20057110
TI  - Turbidity removal effect and surface charge shift for electrochemically treated
      retentate without coagulant addition.
AB  - An electrolytic treatment method promoting dense aggregates was developed in
      order to thicken retentate quickly without coagulant addition. A kaolin
      suspension with a turbidity of 200 NTU with a large fraction of colloidal
      particles was used as the retentate. Comparative testing showed that the
      electrolytic treatment increased aggregate size and enhanced the turbidity
      removal effect up to 75% on average with increasing retention time. Even though
      the Al ion concentration in the treated retentate was much lower than 0.1 mg/L,
      along with the large upward shift of surface charge, the turbidity removal effect
      was enhanced considerably with independently stabilized pH compared with alum as
      the coagulant. Comparison between the charging behaviors indicated that the
      electrochemical treatment generates polymeric Al hydroxide species that form
      adsorption layers with fewer defects, thereby inducing a stronger removal effect.

PMID- 20057111
TI  - Bacterial community structure and diversity during establishment of an anaerobic
      bioreactor to treat swine wastewater.
AB  - An upflow anaerobic sludge blanket (UASB) reactor was successfully established to
      treat swine wastewater. The bacterial structure and biodiversity of activated
      sludge in the anaerobic bioreactor were analyzed using polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE) and amplified 16S rDNA
      restriction analysis (ARDRA). The UASB reactor was acclimatized with swine
      wastewater for a period of 36 days and exhibited an increase in daily COD removal
      rate up to 90% and methane production up to 9.5 L/day for an influent COD of
      3,500 mg/L at the end of the start-up period. The reactor was then run
      continuously with an influent COD of 3,000-6,000 mg/L in the following two months
      of steady operation, reaching COD removal rate of 90-95% and methane production
      of 9.5-13.2 L/day respectively. The results of microbial community analysis
      showed a diversified and abundant bacterial structure and biodiversity during the
      start-up period, which then changed insignificantly in the steady operation
      period. The change patterns of the bacterial population function were similar to
      those of the bioreactor performance, indicating a close relationship between
      bacterial community structure and treatment efficiency.

PMID- 20057112
TI  - Characterization of micro-bubble size distribution and flow configuration in DAF
      contact zone by a non-intrusive image analysis system and tracer tests.
AB  - This paper aims to investigate the influence of some dissolved air flotation
      (DAF) process variables (specifically: the hydraulic detention time in the
      contact zone and the supplied dissolved air concentration) and the pH values, as
      pretreatment chemical variables, on the micro-bubble size distribution (BSD) in a
      DAF contact zone. This work was carried out in a pilot plant where bubbles were
      measured by an appropriate non-intrusive image acquisition system. The results
      show that the obtained diameter ranges were in agreement with values reported in
      the literature (10-100 microm), quite independently of the investigated
      conditions. The linear average diameter varied from 20 to 30 microm, or
      equivalently, the Sauter (d(3,2)) diameter varied from 40 to 50 microm. In all
      investigated conditions, D(50) was between 75% and 95%. The BSD might present
      different profile (with a bimodal curve trend), however, when analyzing the
      volumetric frequency distribution (in some cases with the appearance of peaks in
      diameters ranging from 90-100 microm). Regarding volumetric frequency analysis,
      all the investigated parameters can modify the BSD in DAF contact zone after the
      release point, thus potentially causing changes in DAF kinetics. This finding
      prompts further research in order to verify the effect of these BSD changes on
      solid particle removal efficiency by DAF.

PMID- 20057113
TI  - The best management of SuDS treatment trains: a holistic approach.
AB  - The use of Sustainable Drainage Systems (SuDS) or Best Management Practice (BMP)
      is becoming increasingly common. However, rather than adopting the preferred
      "treatment train" implementation, many developments opt for end of pipe control
      ponds. This paper discusses the use of SuDS in series to form treatment trains
      and compares their potential performance and effectiveness with end of pipe
      solutions. Land-use, site and catchment characteristics have been used alongside
      up-to-date guidance, Infoworks CS and MUSIC to determine whole-life-costs, land
      take, water quality and water quantity for different SuDS combinations. The
      results presented show that the use of a treatment train allows approaches
      differing from the traditional use of single SuDS, either source or "end of
      pipe", to be proposed to treat and attenuate runoff. The outcome is a more
      flexible solution where the footprint allocated to SuDS, costs and water quality
      can be managed differently to satisfy more efficiently the holistically
      stakeholders' objectives.

PMID- 20057114
TI  - Photocatalytic degradation of clofibric acid, carbamazepine and iomeprol using
      conglomerated TiO2 and activated carbon in aqueous suspension.
AB  - The combination of powdered activated carbon (PAC) and TiO(2) has been tested for
      synergistic/antagonistic effects in the photocatalytic degradation of
      carbamazepine, clofibric acid and iomeprol. Synergistic effects are thought to be
      caused by rapid adsorption on the PAC surface followed by diffusion to the TiO(2)
      surface and photocatalytic degradation. The Freundlich constant K(F) was used for
      comparing the sorption properties of the three substances and it was found that
      K(F) for clofibric acid was 3 times lower than for carbamazepine and iomeprol,
      regardless of the kind of PAC used. A PAC with a distinct tendency to form
      conglomerates was selected so that a high percentage of the PAC surface was in
      direct proximity to the TiO(2) surface. The photocatalytic degradation of the
      pharmaceutically active compounds studied followed pseudo-first order kinetics.
      Synergistic effects only occurred for clofibric acid (factor 1.5) and an inverse
      relationship between adsorption affinity and synergistic effects was found. High
      affinity of the target substances to the PAC surface seemed to be
      counterproductive for the photocatalytic degradation.

PMID- 20057115
TI  - Effect of a negatively charged lipid on membrane-lacticin Q interaction and
      resulting pore formation.
AB  - Lacticin Q is an antimicrobial peptide that forms pores on membranes. We
      investigated effects of negatively charged lipids on the binding and pore
      formation of lacticin Q with liposomes by surface plasmon resonance analysis and
      fluorescence dye leakage experiments respectively. Negatively charged lipids
      accelerated the binding of lacticin Q on the membranes and the resulting pore
      formation. However, the acceleration was not an essential factor in the killing
      activity of lacticin Q, since pore-forming activities against electrically
      neutral and negatively charged liposomes occurred similarly.

PMID- 20057116
TI  - Functions of gum arabic and soybean soluble polysaccharide in cooked rice as a
      texture modifier.
AB  - The textural properties of cooked rice were investigated in the presence and the
      absence of gum arabic (GA) and soybean soluble polysaccharide (SSPS). SSPS was
      more effective in increasing the hardness and in decreasing the stickiness of the
      rice grains than GA. For both polysaccharides, the increase in hardness was more
      apparent in the whole body than at the periphery, whereas the decrease in
      stickiness was more apparent at the periphery than in the whole body. SSPS was
      more effective in retarding the gelatinization of rice starch and in lowering the
      elastic characters of the glutinous layer (the materials leached out of the rice
      grains during cooking) along with a decrease in the amount of amylopectin
      leached. The textural hardness of cooked rice was determined by the degree of
      starch gelatinization, whereas the textural stickiness was related to the
      rheological characters of the glutinous layer and the leaching profile of the
      starch components.

PMID- 20057117
TI  - Retarding activity of 6-O-acyl-D-alloses against plant growth.
AB  - The retarding activity of 6-O-dodecanoyl-D-allose against rice growth was higher
      than that of the octanoate and the decanoate. The activities of 6-O-dodecanoyl-D
      glucose, -D-mannose, and -D-galactose against rice seedlings were examined. 6-O
      Dodecanoyl-D-allose exhibited the highest activity, suggesting the importance of
      the alpha-axial hydroxy group at C-3 of D-allose.

PMID- 20057118
TI  - Ethanol stress response in the mRNA flux of Saccharomyces cerevisiae.
AB  - Post-transcriptional regulation as well as transcriptional regulation plays an
      important role in the expression of genes under stressed conditions in
      Saccharomyces cerevisiae. Under stressed conditions caused by heat shock or
      ethanol, yeast cells alter not only their transcriptional patterns but also the
      types of mRNA to be exported from the nucleus in order to adapt rapidly to the
      stress. Under heat-shocked conditions at 42 degrees C, bulk poly (A)(+) mRNA
      accumulates in the nucleus, whereas stress-induced transcripts such as HSP mRNAs
      are efficiently exported. Ethanol stress also causes nuclear accumulation of bulk
      poly (A)(+) mRNA, but elicits a different response regarding the transport of HSP
      mRNAs. Other differences between the heat shock response and the ethanol stress
      response were observed in the nuclear processing of transcripts and in cytosolic
      mRNA flux. This review outlines the regulation of yeast gene expression at the
      mRNA processing and nuclear export steps under ethanol stressed conditions, and
      discusses how to improve the capabilities of brewer's yeast cells.

PMID- 20057119
TI  - Bacillus subtilis spore coat protein LipC is a phospholipase B.
AB  - In Bacillus subtilis, the germination-related lipase LipC is located in the spore
      coat, and mutant spores are defective in L-alanine-stimulated germination. To
      determine the physiological role of LipC, the recombinant LipC expressed in
      Escherichia coli was purified and characterized. The enzyme hydrolyzes p
      nitrophenyl ester substrates with various acyl-chain lengths. Thin-layer
      chromatography and gas chromatography-mass spectrometry analysis indicated that
      LipC cleaves the fatty acids at the sn-1 and sn-2 positions of phospholipids as
      phospholipase B, and that the enzyme shows no selectivity for the polar head
      groups of lipid molecules. When the amounts of free fatty acids in dormant wild
      type and lipC mutant (YCSKd) spores were measured, the amount of free fatty acids
      in the YCSKd spores was about 35% less than in the wild-type spores. These
      results suggest the possibility that Bacillus subtilis LipC plays an important
      role in the degradation of the outer spore membrane during sporulation.

PMID- 20057120
TI  - Novel compounds of octahydroheptaprenyl mycolic acyl ester and monocyclic C35
      terpene, heptaprenylcycline B, from non-pathogenic mycobacterium species.
AB  - A search for C(35)-terpenes from non-saponified extracts of 12 non-pathogenic
      Mycobacterium species was carried out. Octahydroheptaprenyl mycolic acyl esters
      were isolated from M. chlorophenolicum cells which were also found from M.
      thermoresistibile, M. vanbaalenii, M. aichiense, M. smegmatis, and M.
      parafortuitum. This is the first report on a polyprenol esterified by a mycolate.
      A novel monocyclic C(35)-terpene possessing a ketone, named heptaprenylcycline B,
      was isolated, which was detected from M. chlorophenolicum and M. vanbaalenii. The
      biosynthetic pathway to heptaprenylcycline B was investigated with ancymidol
      which acts as an inhibitor of a P450 monooxygenase. This experiment suggested
      that the P450 monooxygenase may be responsible for the production of
      heptaprenylcycline B.

PMID- 20057121
TI  - Comparison of the effects on lipid metabolism of dietary methionine and cystine
      between hepatoma-bearing and normal rats.
AB  - The effects of dietary supplementation with methionine and cystine on lipid
      metabolism, including the serum lipid concentration, were studied in Donryu rats
      subcutaneously implanted with an ascites hepatoma cell line (AH109A) for
      comparison with normal rats. A diet supplemented with 1.2% L-methionine or L
      cystine to 20% casein was found to suppress the hepatoma-induced increases in
      serum triglyceride and total cholesterol concentration. The lipoprotein lipase
      activity in tissues was enhanced by dietary methionine and cystine, with no
      change in the mRNA level. Dietary methionine and cystine increased bile acid
      excretion into the feces with enhanced hepatic cholesterol 7alpha-hydroxylase
      activity. Dietary methionine and cystine affected the lipid metabolism
      differently in normal rats from hepatoma-bearing rats. These results suggest that
      dietary methionine and cystine each had a hypolipidemic effect against cancer
      induced hyperlipidemia, and that the different actions observed in the hepatoma
      bearing and normal rats may have been due to a metabolic abnormality caused by
      the cancer.

PMID- 20057122
TI  - Reaction products of gamma-tocopherol with (E)-4-oxo-2-nonenal in acidic
      acetonitrile.
AB  - gamma-Tocopherol was reacted with (E)-4-oxo-2-nonenal (ONE) at 37 degrees C in an
      acidic acetonitrile solution. The reaction products were isolated by reversed
      phase high-performance liquid chromatography and their structures were
      characterized to be 5-substituted gamma-tocopherols: 5-(1-(furan-2-yl)pentyl)
      gamma-tocopherol (1), 3-(1-butyl-4,5,7-trimethyl-7-(4,8,12-trimethyltridecyl)-8,9
      dihydro-7H-furo[3,2-f]chromen-2yl)propanal (2), and 1-(1-butyl-4,5,7-trimethyl-7
      (4,8,12-trimethyltridecyl)-8,9-dihydro-7H-furo[3,2-f]chromen-2-yl)-4-(furan-2
      yl)octan-3-one (3). Compound 1 was the predominant product under the mild acidic
      conditions, whereas compounds 2 and 3 were relatively stable and accumulated
      during the reaction. Compound 1 was detected as the product when gamma-tocopherol
      and ONE were incubated in methyl linoleate in the presence of dicetyl phosphate.
      The results indicate that gamma-tocopherol may trap ONE under acidic conditions
      of lipid peroxidation.

PMID- 20057123
TI  - Phenolic inhibitors of chemical and enzymatic oxidation in the leaves of Myrica
      rubra.
AB  - Potent inhibitory activity of the leaves of Myrica rubra against both chemical
      and enzymatic (tyrosinase and lipoxygenase) oxidation was found in our project to
      develop utility of unused and rarely used plant resources in the local area. A
      constituent analysis of the most active ethyl acetate-soluble part of a methanol
      extract of the leaves clarified the structures of eight major compounds. The
      tyrosinase and lipoxygenase inhibitory activities and DPPH radical scavenging
      activity of the isolated compounds were measured as indicators of the inhibitory
      capacity against the enzymatic and chemical oxidation of food. The obtained data
      indicate that the chemical and enzymatic (lipoxygenase and tyrosinase)
      antioxidant activities of the leaves mainly depended on the galloyl flavonoid
      derivatives.

PMID- 20057124
TI  - Characterization of a cysteine-rich protein specifically expressed in the silk
      gland of caddisfly Stenopsyche marmorata (Trichoptera; Stenopsychidae).
AB  - A novel protein, Smsp-72k, was found to be selectively expressed in the silk
      gland of aquatic larvae of the Stenopsychid caddisfly (Stenopsyche marmorata).
      The protein was characterized by an abundance of cysteine (13.97%) and charged
      residues (47.21%). Amino acids with hydroxyl side-chains accounted for an
      additional 10% of the Smsp-72k protein, with serine at 4.4% and threonine at
      5.6%. A cysteine-rich repetitive sequence is common to many potential and known
      underwater adhesive/cement proteins and cell-cell adhesion molecules. We
      hypothesized that Smsp-72k is an adhesive/cement protein that increases the
      adhesiveness of the silk fiber of S. marmorata. The hydroxyl groups of Smsp-72k
      might form a link with the heavy chain fibroin of S. marmorata, removing the weak
      boundary-water layer and allowing the spreading of the silk protein onto the
      surface of the substratum during the process of adhesion.

PMID- 20057125
TI  - AtKUP/HAK/KT9, a K+ transporter from Arabidopsis thaliana, mediates Cs+ uptake in
      Escherichia coli.
AB  - Although cesium is known to be absorbed by plants, the pathway by which cesium
      enters has not been identified. We found that the AtKUP/HAK/KT9 gene from
      Arabidopsis thaliana was functionally expressed in a potassium transport
      deficient Escherichia coli mutant. AtKUP/HAK/KT9 mediated potassium uptake as
      well as cesium transport. We found that AtKUP/HAK/KT9 might be involved in the
      pathway in questions.

PMID- 20057126
TI  - Investigation of multiple forms of Tri a Bd 27K, a major wheat allergen, by
      immunoblotting analysis.
AB  - Tri a Bd 27K, a major wheat allergen, is a glycoprotein. Tri a Bd 27K was found
      to occur in multiple forms by two-dimensional polyacrylamide gel electrophoresis
      and immunoblotting with a monoclonal antibody against the allergen. Furthermore,
      it was found that only Tri a Bd 27K components, which have N-linked glycan
      moieties with fucose residues, bound to IgE antibodies in the sera of wheat
      sensitive patients.

PMID- 20057127
TI  - Characterization of the palH gene from Aspergillus oryzae.
AB  - We disrupted the palH gene, which is known to participate in the ambient pH
      signal transduction pathway, in Aspergillus oryzae. palH disruption caused
      significant decreases in pacC expression and alkaline protease activity. Hence we
      believe that palH plays a very important role in controlling the alkaline
      protease level in A. oryzae.

PMID- 20057128
TI  - Effects of single and combined administration of fermented barley extract and
      gamma-aminobutyric acid on the development of atopic dermatitis in NC/Nga mice.
AB  - We examined the effects single and combined administration of fermented barley
      extract P (FBEP), prepared from barley-shochu distillery by-products, and gamma
      aminobutyric acid (GABA) on the development of atopic dermatitis (AD)-like skin
      lesions in NC/Nga mice. Single administration of FBEP and GABA dose-dependently
      reduced the development of AD-like skin lesions in mice. GABA reduced the
      development of AD-like skin lesions by suppressing serum immunoglobulin E (IgE)
      and splenocyte interleukin (IL)-4 production, while FBEP reduced skin lesions
      without affecting the IgE or cytokine production. However, in mice with induced
      AD-like skin lesions, combined administration of FBEP and GABA decreased serum
      IgE levels and splenic cell IL-4 production, and increased splenic cell
      interferon-gamma production. These results suggest that combined administration
      of FBEP and GABA alleviated AD-like skin lesions in the NC/Nga mice by adjusting
      the Th1/Th2 balance to a Th1-predominant immune response.

PMID- 20057129
TI  - Purification and properties of a nuclease from the fruit body of Tricholoma
      matsutake.
AB  - A nuclease was purified from the fruit body of Tricholoma matsutake. The
      molecular mass was 38 kDa. The optimum pH of the nuclease was about 8.0. Its
      activity was inhibited by GTP. The nuclease cleaved RNA and heat-denatured DNA
      endonucleolytically to produce 5'-mononucleotide, and showed 3'-nucleotidase
      activity. The amino acid sequence up to seven amino acids from the N-terminus was
      NH(2)-APPPSSN.

PMID- 20057130
TI  - Poly(3-hydroxybutyrate) production by isolated Halomonas sp. KM-1 using waste
      glycerol.
AB  - Biodiesel fuel is favored as a type of carbon neutral energy. To popularize its
      usage, by-product waste glycerol utilization is a critical problem. We tried to
      isolate waste glycerol utilizing bacteria, and obtained the alkalo- and halophile
      bacteria Halomonas sp. KM-1. This strain produced bioplastic poly(3
      hydroxybutyrate) (PHB) in a simple medium and diluted waste glycerol as a sole
      carbon source.

PMID- 20057131
TI  - Effect of glycerophospholipid class on the beta-carotene uptake by human
      intestinal Caco-2 cells.
AB  - The effects were evaluated of various glycerophospholipids on the uptake of beta
      carotene solubilized in mixed micelles by human intestinal Caco-2 cells.
      Phosphatidylethanolamine markedly enhanced the transfer of beta-carotene from the
      micelles to the cells, whereas phosphatidylcholine suppressed it. All the
      lysoglycerophospholipids enhanced the transfer, irrespective of the polar head
      group. Glycerophospholipids therefore have the potential to modify the intestinal
      absorption of carotenoids.

PMID- 20057132
TI  - Enantioselective syntheses of pachastrissamine and jaspine A via
      hydroxylactonization of a chiral epoxy ester.
AB  - A new enantioselective total synthesis of pachastrissamine (jaspine B) was
      achieved from a known alpha,beta-unsaturated aldehyde by utilizing Cordova's
      asymmetric epoxidation as the chirality-inducing step. The 2,3-cis
      stereochemistry of pachastrissamine was established via intramolecular epoxide
      ring opening of a gamma,delta-epoxy-alpha,beta-unsaturated ester intermediate
      coupled with oxy-Michael cyclization. Treatment of pachastrissamine with
      tetrahydro-2-furanol under acidic conditions led to smooth oxazolidine ring
      formation, furnishing jaspine A in a high yield.

PMID- 20057133
TI  - Rhodococcus baikonurensis BTM4c, a boron-tolerant actinobacterial strain isolated
      from soil.
AB  - By screening a bacterial population from the soil in Tokyo, Japan, we isolated a
      boron-tolerant bacterium, strain BTM4c. Strain BTM4c grew under the boron excess
      conditions with 100 mM boric acid, which is generally toxic to bacteria.
      Molecular phylogenetic, chemotaxonomic, and physiological data showed that the
      strain belongs to the genus Rhodococcus, and is to be identified as Rhodococcus
      baikonurensis.

PMID- 20057134
TI  - Improved synthesis of three methyl-branched pheromone components produced by the
      female lichen moth.
AB  - Female moths of Lyclene dharma dharma (Arctiidae, Lithosiinae) produce a novel
      sex pheromone composed of three methyl-branched ketones: 6-methyl-2-octadecanone
      (I), 14-methyl-2-octadecanone (II), and 6,14-dimethyl-2-octadecanone (III). Their
      structures were confirmed by syntheses accomplished by a different route for each
      component. In order to obtain a sufficient amount of the synthetic pheromone, we
      developed new routes via methyl-branched 1-alkenes: 6-methyl-1-octadecene (1), 14
      methyl-1-octadecene (2), and 6,14-dimethyl-1-octadecene (3). Compound 1 was
      synthesized by coupling between a C(10)-chain bromide and a 3-methyl-branched
      C(8) unit (A) prepared from 3-methyl-1,5-pentanediol, 2, by coupling between a
      C(11)-chain bromide and a 3-methyl-branched C(7) unit (B) prepared from 2
      hexanone, and 3, by connecting A and B, using propargyl alcohol as a C(3)
      linchpin. The use of 3-chloro-1-propanol and tert-butyl acetoacetate as the
      linchpin was also examined to connect the two synthetic blocks in the synthesis
      of 3. Components I-III were obtained by Wacker oxidation of the corresponding 1
      alkenes 1-3 in good yields.

PMID- 20057135
TI  - A novel L-amino acid ligase from Bacillus subtilis NBRC3134 catalyzed
      oligopeptide synthesis.
AB  - L-Amino acid ligase catalyzes dipeptide synthesis from unprotected L-amino acids
      in an ATP-dependent manner. We have purified a new L-amino acid ligase, RizA,
      which synthesizes dipeptides whose N-terminus is Arg, from Bacillus subtilis
      NBRC3134, a microorganism that produces a rhizocticin peptide antibiotic. It was
      suggested that RizA is probably involved in rhizocticin biosynthesis. In this
      study, we performed sequence analysis of unknown regions around rizA, and newly
      identified a gene that encodes a protein that possesses an ATP-grasp motif
      upstream of rizA. This gene was designated rizB, and its recombinant protein was
      prepared. Recombinant RizB synthesized homo-oligomers of branched-chain L-amino
      acids and L-methionine consisting of two to five amino acids in an ATP-dependent
      manner. RizB also synthesized various heteropeptides. Further examination showed
      that RizB might elongate a peptide chain at the N-terminus. This is the first
      report on an L-amino acid ligase catalyzing oligopeptide synthesis.

PMID- 20057136
TI  - Studies on natural p-terphenyls: total syntheses of vialinin A and terrestrin B.
AB  - A powerful inhibitor of TNF-alpha production, vialinin A, was synthesized from
      sesamol through a series of reactions involving double Suzuki-Miyaura coupling,
      2,3-dichloro-5,6-dicyano-1,4-benzoquino (DDQ) mediated de-methoxymethylation and
      oxidative removal of methylene acetal by lead tetraacetate. The synthetic method
      also made it possible to prepare a related compound, terrestrin B.

PMID- 20057137
TI  - Inhibitory effect of curcumin on IMP dehydrogenase, the target for anticancer and
      antiviral chemotherapy agents.
AB  - Inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in the de
      novo synthesis of guanine nucleotides, is a therapeutic target for anticancer and
      antiviral agents. Among the 15 different polyphenols examined, curcumin was found
      to have an inhibitory effect on the IMPDH activity in both a competitive and
      uncompetitive manner and to suppress the cellular GTP level in HT-29 colon
      carcinoma cells.

PMID- 20057138
TI  - Purification and characterization of an N-terminal acidic amino acid-specific
      aminopeptidase from soybean cotyledons (Glycine max).
AB  - A novel enzyme that catalyzes the efficient hydrolysis of Glu-Glu was isolated
      from soybean cotyledons by ammonium sulfate fractionation and successive column
      chromatographies of Q-sepharose, Phenyl sepharose, and Superdex 200. The apparent
      molecular mass of this enzyme was found to be 56 kDa and 510 kDa by SDS
      polyacrylamide gel electrophoresis and Superdex 200 HR 10/30 column
      chromatography respectively. The enzyme had high activity against Glu-p
      nitroanilide (pNA) and Asp-pNA, whereas Leu-pNA, Phe-pNA, Ala-pNA, and Pro-pNA
      were not hydrolyzed. The synthetic dipeptides Glu-Xxx and Asp-Xxx were
      hydrolyzed, but Xxx-Glu was not. The digestion of a Glu-rich oligopeptide,
      chromogranin A (Glu-Glu-Glu-Glu-Glu-Met-Ala-Val-Val-Pro-Gln-Gly-Leu-Phe-Arg-Gly
      NH(2)) using this purified enzyme was also investigated. Glutamic acid residues
      were cleaved one by one from the N-terminus. These observations indicate that the
      enzyme removes glutamyl or aspartyl residues from N-terminal acidic amino acid
      containing peptides. It is thought that it was an N-terminal acidic amino acid
      specific aminopeptidase from a plant.

PMID- 20057139
TI  - Purification and biochemical characterization of recombinant rice UDP
      arabinopyranose mutase generated in insect cells.
AB  - Plants utilize UDP-arabinofuranose (UDP-Araf) in the biosynthesis of Araf
      containing complex carbohydrates. UDP-Araf is synthesized from UDP
      arabinopyranose by UDP-arabinopyranose mutases (UAMs). Here we describe the
      heterologous expression of rice (Oryza sativa) UAM genes in insect cells and
      report some of their enzymatic properties. Recombinant UAMs might serve as useful
      tools for the biosynthesis of UDP-Araf and might be better than chemical
      synthesis.

PMID- 20057140
TI  - A silent mutation made possible efficient production of active human Frk tyrosine
      kinase in Escherichia coli.
AB  - Fyn-related kinase (Frk) was first identified using human breast cancer cells. It
      shares 51% identity with c-Src. Like all members of the Src family, Frk is
      thought to cause several cancers via dysregulations in signal transduction from
      cell-surface receptors. The excess activity of Frk on beta-cells has a crucial
      role in type-I diabetes. A silent mutation at Ile229 conferred a bacterial
      expression system on the kinase domains of Frk, which allowed for the quick
      expression and purification of one unphosphorylated and two mono-phosphorylated
      kinase domains. The C-terminal catalytic segment of the human Frk kinase
      conjugating hexahistidine purification tag (His-tag) was expressed in Escherichia
      coli. After first-step purification utilizing the His-tag, an anion-exchange
      chromatogram yielded three major peaks that had distinguishable phosphorylation
      characteristics as judged by Western blot analysis and measurement of kinase
      activity. This result of active protein production should promote drug discovery
      studies, including highthrough-put screening and structure-based drug design.

PMID- 20057141
TI  - Cell size regulation during telomere-directed senescence in Saccharomyces
      cerevisiae.
AB  - DNA replication without telomerase leads to telomere shortening and induces
      replicative senescence. We found that in a telomerase-deficient budding yeast
      mutant, the volume of each telomere-shortened cell increased as its growth
      capacity decreased, and that this process was associated with changes in vacuolar
      morphology. Senescence-induced cell expansion required Mec1, a DNA damage
      responsive kinase, but not vacuolar SNARE Vam3.

PMID- 20057142
TI  - Development of coenzyme Q10-enriched rice using sugary and shrunken mutants.
AB  - Coenzyme Q10 (CoQ10) is a popular food supplement. Earlier, we successfully
      produced CoQ10 in rice, which normally produces predominately CoQ9. Here we
      developed efficient production of CoQ10 in rice by introducing the gene for
      decaprenyl diphosphate synthase into rice sugary and shrunken mutants. These
      rices produced 1.3 to 1.6 times as much CoQ10 as the earlier enriched rice did.

PMID- 20057143
TI  - Crystal structure of cold-active alkaline phosphatase from the psychrophile
      Shewanella sp.
AB  - The crystal structure of a cold-active alkaline phosphatase from a psychrophile,
      Shewanella sp. (SCAP), was solved at 2.2 A. A refined model showed a homodimer
      with six metal-ligand sites. The arrangement of the catalytic residues resembled
      those of alkaline phosphatases (APs), suggesting that the reaction mechanism of
      SCAP was fundamentally identical to those of other APs. SCAP had two distinct
      structural features: (i) a loop with Arg122 that bound to the phosphate moiety of
      the substrate suffered no constraints from the linkage to other secondary
      structures, and (ii) Mg3-ligand His109 was considered to undergo repulsive effect
      with neighboring Trp228. The local flexibility led by these features might be an
      important factor in the high catalytic efficiency of SCAP at low temperatures.

PMID- 20057144
TI  - Defective dynamic properties of human cardiac troponin mutations.
AB  - Mutations in Troponin I (TnI) and Troponin T (TnT) are closely linked to familial
      hypertrophic cardiomyopathy (FHC) and hypertrophic cardiomyopathy (HCM), but the
      underlying molecular mechanism is not yet well understood. There might be a close
      link between the defective dynamic properties and the functional aberrations of
      hcTroponin. To prove this hypothesis, we undertook detailed NMR relaxation
      measurements of [(2)H, (13)C, (15)N] labeled proteins reconstituted into
      hcTroponin in both the Ca(2+)- and the Mg(2+)-loaded state. The wild-type TnI and
      two FHC causing mutations, TnI(G203S) and TnI(DeltaK183), were investigated. To
      ensure that defective dynamic properties are not only a particular feature for
      mutations in the flexible part of TnI, measurements of the TnT mutation
      TnT(R278P) were also performed. For all mutations significant dynamic changes in
      the area for Troponin C (TnC) and actin-Tm binding were obtained. These
      measurements provide important information to understand the functional
      aberrations of FHC and HCM causing mutation in human cardiac Troponin (hcTn).

PMID- 20057145
TI  - Culm in rice straw as a new source for sugar recovery via enzymatic
      saccharification.
AB  - Rice straw was manually dissected and two main fractions were recovered: a culm
      and a leaf sheath/blade fraction, in order to evaluate their potential as
      feedstocks for the recovery of fermentable sugars. In the case of cv. Koshihikari
      and Milkyqueen, most soft carbohydrates (SCs: glucose, fructose, sucrose, starch,
      and beta-1,3-1,4-glucan) were present in the culms, reaching 47.9% and 89.2% of
      total SCs in the two main fractions. The results also indicated that beta-glucans
      (cellulose and beta-1,3-1,4-glucan) and xylan in the culms were more susceptible
      to direct enzymatic attack than those in the leaf sheath/blades. Thus the culm
      has high potential as a new feedstock for the extraction of fermentable sugars in
      a concentrated form, as compared to whole rice straw and the leaf sheath/blade.
      In this study, a novel method of separating a culm from the whole rice straw by
      means of wind power was also evaluated.

PMID- 20057146
TI  - Electromyographic measurement of eating behaviors for buckwheat noodles.
AB  - The objective of this study was to analyze human eating behaviors in chewing and
      slurping buckwheat noodles. We used electromyography to measure the activity of
      the jaw-closing, jaw-opening, and lip-closing muscles while healthy adults ate
      one mouthful of buckwheat noodles. Slurping the noodles required a longer
      mastication period but smaller muscle activity per movement than chewing the same
      samples. Total muscle activity was greater in slurping. Slurping also showed a
      longer average cycle time but greater variances in the cycle time than rhythmical
      chewing. The mechanical properties of buckwheat noodles significantly differed
      between the noodle types (half-raw and dry), but the human mastication variables
      for the two types of noodles were not significantly changed within a subject.
      Both types of noodles kept for 10 min at 23 degrees C after being cooked could be
      consumed with less mastication effort than those immediately served, and this
      observation corresponded to softening of the noodles during the standing time.

PMID- 20057147
TI  - Effects of feeding hexane-extracts of a shochu distillery by-product on skeletal
      muscle protein degradation in broiler chicken.
AB  - We have found that shochu distillery by-product (SDBP) contains a growth
      promoting factor that can be extracted with ether. In the present study, we
      administered hexane-extracts of SDBP (HSDBP) to broiler chickens and observed
      changes in skeletal muscle protein degradation in order to clarify the mechanism
      of growth promotion due to SDBP feeding. The pectoralis superficial muscle weight
      was significantly increased by HSDBP feeding. Plasma N(tau)-methylhistidine
      concentration was significantly decreased by HSDBP, showing that the rate of
      muscle protein degradation decreased. It was also found that the expression of
      mRNA of ubiquitin-proteasome system and calpain was decreased by HSDBP. These
      results indicate that growth promotion due to SDBP is caused by suppression of
      skeletal muscle protein degradation, which is related to the ubiquitin-ptoteasome
      system and calpain.

PMID- 20057148
TI  - Oral intake of Lactobacillus helveticus-fermented milk whey decreased
      transepidermal water loss and prevented the onset of sodium dodecylsulfate
      induced dermatitis in mice.
AB  - We investigated the effects of oral intake of Lactobacillus helveticus-fermented
      milk whey on the intact and sodium dodecylsulfate (SDS)-exposed skin of Hos:HR-1
      hairless mice. The mice were allowed to drink 10% L. helveticus-fermented milk
      whey in distilled water ad libitum for 5 weeks. SDS solution was topically
      applied to the dorsal skin at 4 weeks, leading to the development of dermatitis.
      The skin moisture content, transepidermal water loss, and sizes of the dermatitis
      areas were periodically measured. Compared with oral intake of water alone, oral
      intake of water containing L. helveticus-fermented milk whey for 4 weeks
      significantly lowered transepidermal water loss from intact skin, significantly
      reduced in size the areas of early SDS-induced dermatitis, and ameliorated both
      the SDS-induced decrease in moisture content and the increase in transepidermal
      water loss. These results suggest that oral intake of L. helveticus-fermented
      milk whey might be effective in promoting the epidermal barrier function and in
      preventing the onset of dermatitis.

PMID- 20057149
TI  - The inhibitory mechanisms of the tyrosine kinase inhibitors herbimycin a,
      genistein, and tyrphostin B48 with regard to the function of the aryl hydrocarbon
      receptor in Caco-2 cells.
AB  - The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated
      by dioxin and related xenobiotics. Although the activation of AhR is inhibited by
      tyrosine kinase inhibitors, the molecular mechanism has not been clarified. In
      the current study, the inhibitory mechanisms of several inhibitors of tyrosine
      kinase, herbimycin A, genistein, and tyrphostin B48, on AhR activation was
      analyzed in human Caco-2 cells. All the inhibitors suppressed the transcriptional
      activation of AhR induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
      Herbimycin A induced down-regulation of the AhR protein by inhibiting its
      molecular chaperone heat shock protein 90 (HSP90). In contrast, genistein and
      tyrphostin B48 inhibited the nuclear localization of AhR induced by TCDD,
      although the amount of AhR protein was not altered. The inhibitory effects of
      genistein and tyrphostin B48 on endogenous tyrosine kinase activity were
      evaluated by detection of alterations in the tyrosine phosphorylation states of
      cellular proteins.

PMID- 20057150
TI  - Isolation and properties of malic enzyme and its gene in Rhodopseudomonas
      palustris No. 7.
AB  - Malic enzyme (ME) was purified as an electrophoretically homogenous protein from
      Rhodopseudomonas palustris No. 7. The molecular weight of ME was estimated to be
      650 kDa and that of its subunit, 86 kDa. ME activity was remarkably enhanced by
      di- and mono-valent cations, and the K(a) values for Mg(2+) and NH(4)(+) were
      0.26 and 0.56 mM respectively. Purified ME used both NAD(+) and NADP(+) as
      electron acceptors, with K(m) values of 0.11 and 1.8 mM. The K(m) value for L
      malate was 1.7 mM using NAD(+) as electron acceptor. Gene cloning of the ME
      indicated that the ME from R. palustris strain No. 7 was composed of 774 amino
      acids encompassing the ME and phosphotransacetylase domains, although purified ME
      displayed no phosphotransacetylase activity. ME activity was inhibited by acetyl
      CoA, oxaloacetate, and fructose-6-phosphate. These results suggest that ME plays
      an important role in the metabolic regulation of R. palustris No. 7 under
      photoheterotrophic conditions.

PMID- 20057151
TI  - Transcriptional regulation of cGMP-dependent protein kinase II (cGK-II) in
      chondrocytes.
AB  - The C-type natriuretic peptide/natriuretic peptide receptor-B/cGMP pathway plays
      an important role in the regulation of endochondral ossification. In
      chondrocytes, the physiological effect of cGMP is mediated primarily by the
      activation of cGMP-dependent protein kinase II (cGK-II). In this study, we
      investigated the transcriptional regulation of cGK-II in chondrocytes. The
      expression pattern of cGK-II transcripts was examined during chondrogenic
      differentiation of ATDC5 cells. cGK-II mRNA was not detectable in
      undifferentiated cells, but increased dramatically prior to differentiation to
      the hypertrophic stage. To analyze the transcriptional regulation of cGK-II, the
      5'-flanking region of the mouse cGK-II gene was isolated and characterized. The
      promoter activity of the cGK-II gene decreased markedly following deletion and
      mutagenesis of the putative Nkx-binding site between nucleotide positions -292
      and -286. These results suggest that the homeobox gene Nkx family is critical for
      the transcriptional regulation of cGK-II during chondrogenesis.

PMID- 20057152
TI  - Microbial conversion of rare ginsenoside Rf to 20(S)-protopanaxatriol by
      Aspergillus niger.
AB  - In this study, rare ginsenoside Rf was transformed into 20(S)-protopanaxatriol
      (PPT(S)) by glycosidase from Aspergillus niger. By investing the reaction
      conditions, the optimal conditions were obtained, as follows: pH 5.0, temperature
      55 degrees C, and substrate concentration 1.25 mmol/l. Under optimal conditions,
      PPT(S) (1.13 micromol) prepared from 1.25 mumol Rf showed a higher yield (90.4%).
      The enzymatic reaction was analyzed by reversed-phase HPLC, suggesting the
      transformation pathway: Rf-->Rh1(S)-->PPT(S).

PMID- 20057153
TI  - Roles of DNA repair proteins in telomere maintenance.
AB  - Telomeres are protected and maintained by telomere-specific proteins. In
      addition, proteins involved in DNA repair, such as Mre11-Rad50-Nbs1 complex, RPA,
      and RecQ helicase, are also involved in telomere maintenance. In this review, the
      roles of these proteins in telomere maintenance and their functional
      relationships to the telomere-specific proteins will be discussed.

PMID- 20057154
TI  - Evaluation of resveratrol oxidation in vitro and the crucial role of bicarbonate
      ions.
AB  - Polyphenols can oxidize in culture medium and produce artifacts in cell culture
      studies. However, the extent and mechanism of the oxidation of resveratrol, a
      polyphenol abundant in red wine, is unclear. We investigated the oxidation of
      resveratrol in vitro and the effects of various components of the culture medium
      on the degradation of resveratrol and the production of H(2)O(2). We found that
      96% of resveratrol at a concentration of 200 microM was degraded in Base Modified
      Eagle Medium after 24 h of incubation at 37 degrees C, producing about 90 microM
      of H(2)O(2). Including sodium bicarbonate in the medium markedly stimulated
      resveratrol degradation and H(2)O(2) production. In sum, we found that
      bicarbonate ions played a crucial role in the oxidative degradation of
      resveratrol in vitro, and that the degradation of resveratrol can be avoided by
      withdrawing sodium bicarbonate from the medium. A mechanism for the oxidation of
      resveratrol is proposed.

PMID- 20057155
TI  - Potential of coriander (Coriandrum sativum) oil as a natural antimicrobial
      compound in controlling Campylobacter jejuni in raw meat.
AB  - Twelve essential oils were tested in vitro for antimicrobial activities against
      several strains of Campylobacter jejuni, a pathogen causing food-borne diseases
      worldwide. Using disk diffusion and minimal inhibitory concentration
      determination assays, we noted that coriander oil exhibited the strongest
      antimicrobial activity against all tested strains. The oil had a bactericidal
      effect on the target bacteria. In evaluating the antimicrobial potency of
      coriander oil against C. jejuni on beef and chicken meat at 4 degrees C and 32
      degrees C, it was found that the oil reduced the bacterial cell load in a dose
      dependent manner. The type of meat and temperature did not influence the
      antimicrobial activity of the oil. This study indicates the potential of
      coriander oil to serve as a natural antimicrobial compound against C. jejuni in
      food.

PMID- 20057156
TI  - High-throughput and highly sensitive analysis method for polyisoprene in plants
      by pyrolysis-gas chromatography/mass spectrometry.
AB  - Natural polyisoprene is a biopolymer consisting of isoprene units (C(5)H(8)) that
      is used commercially in household, medical, and industrial materials. For the
      management of natural polyisoprene production, the selection of high-yield
      polyisoprene-producing trees, and an understanding of polyisoprene biosynthesis,
      a high-throughput and highly sensitive screening method for the quantification of
      polyisoprene is required. In this study, we examined pyrolysates from
      polyisoprenes, polyprenols, carotenoids, ubiquinone (CoQ-10), and sterols by
      pyrolysis gas chromatography/mass spectrometry (PyGC/MS) and determined that the
      amounts of isoprene and limonene released from polyprenols and polyisoprenes were
      dependent upon their molecular weights. Based on these results, we developed a
      relative quantification method for polyisoprene in leaves by direct analysis of 1
      mg of leaves using PyGC/MS. This novel quantification method eliminated
      extraction steps and can be used in the measurement of polyisoprene contents in
      Eucommia ulmoides and Hevea brasiliensis.

PMID- 20057157
TI  - Does obesity attenuate the effect of metabolic syndrome on chronic kidney disease
      in patients with coronary artery disease? Report from China heart survey.
AB  - BACKGROUND: The present study explored the relationship between metabolic
      syndrome (MetS) and chronic kidney disease (CKD) in patients with coronary artery
      disease (CAD) in China. METHODS AND RESULTS: The prevalence of MetS and CKD were
      determined in 3,465 participants with CAD from the China Heart Survey, from June
      1(st) to August 31(st) 2005. The relationship between MetS and CKD was analyzed.
      The prevalence of MetS and CKD was 53.0% and 21.1%, respectively. Patients with
      MetS had a higher prevalence of CKD than those without MetS. All traits of MetS
      except central obesity were statistically significantly associated with CKD. The
      multivariate-adjusted odds ratio (OR) of CKD in participants with and without
      MetS was 1.27 (95% confidence interval (CI) 1.07-1.51). In the multivariate
      adjusted model, patients with 3 MetS components, excluding central obesity, had a
      higher OR for CKD (OR 2.17, 95%CI 1.21-3.88). CONCLUSIONS: MetS is a
      significantly higher risk factor for CKD in patients with CAD. Central obesity
      might attenuate the effect of MetS on CKD in patients with CKD, regardless of the
      number of MetS components.

PMID- 20057158
TI  - Coronary score adds prognostic information for patients with acute coronary
      syndrome.
AB  - BACKGROUND: The aim of the present study was to explore the association of 3
      coronary scores with major adverse cardiovascular events (MACE) in patients with
      acute coronary syndrome (ACS). METHODS AND RESULTS: The 958 consecutive patients
      with ACS were followed up until either MACE or 31(st) December 2008 occurred; 257
      patients reached clinical endpoints. Cox regression analysis demonstrated that
      the Gensini score was associated with 90-day MACE (relative risk (RR) 1.021,
      P=0.004), 6-month MACE (RR 1.021, P<0.001), 1-year MACE (RR 1.017, P=0.002), and
      MACE during follow-up (RR 1.010, P=0.040). Leaman score was associated with 90
      day MACE (RR 1.094, P=0.014), 6-month MACE (RR 1.098, P=0.002), and 1-year MACE
      (RR 1.074, P=0.009). The logistic regression analysis demonstrated that the
      Gensini score (odds ratio (OR) 1.037, P=0.001), Leaman score (OR 1.165, P=0.007)
      and American College of Cardiology/American Heart Association (ACC/AHA) score (OR
      1.235, P=0.025) were all associated with cardiogenic death. CONCLUSIONS: The
      Gensini score provides more valuable prognostic information on cardiovascular
      risk than either the Leaman or ACC/AHA score in patients with ACS.

PMID- 20057159
TI  - Change in ischemia-modified albumin and its clinical significance during exercise
      stress testing.
AB  - BACKGROUND: There is little data about the additive effects of ischemia-modified
      albumin (IMA) on the exercise stress test (EST) used for the screening of
      ischemic heart disease. The relationship between myocardial ischemic burden and
      the change in IMA (DeltaIMA) during EST was investigated. METHODS AND RESULTS:
      EST was performed using the Bruce protocol to evaluate chest pain or exertional
      dyspnea in 155 patients (men 89, 53+/-13 years). Blood samples for IMA were
      obtained before and immediately after EST. According to the EST results and the
      pattern of DeltaIMA, patients were categorized into 3 groups (none was classified
      as EST(-)/DeltaIMA(+)): (1) (EST(-); (2) EST(+)/DeltaIMA(-); and (3)
      EST(+)/DeltaIMA(+). After EST, 60 of 155 (38.7%) patients were EST(+) and 14/60
      (23.3%) were EST(+)/DeltaIMA(+). Duke treadmill score was significantly lower in
      the EST(+)/DeltaIMA(+) group compared with the other groups (-9.0+/-7.9, -1.7+/
      4.2, 6.7+/-4.4, respectively, P<0.001); 43/60 (72%) patients with EST(+)
      underwent coronary angiography and the proportion of patients with a large
      ischemic burden was higher in the EST(+)/DeltaIMA(+)group compared with the
      EST(+)/DeltaIMA(-) group (72.7% vs 15.6%, P=0.001). CONCLUSIONS: Increased IMA
      after EST suggests a large ischemic burden in coronary artery disease, so the
      DeltaIMA during EST may be useful for predicting the severity of myocardial
      ischemia.

PMID- 20057160
TI  - Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in
      hearts of rats with autoimmune myocarditis and in human myocarditis.
AB  - BACKGROUND: Lipocalin-2/neutrophil gelatinase-B associated lipocalin (Lcn2/NGAL)
      is involved in the transport of iron and seems to play an important role in
      inflammation. A recent study has reported that it is also expressed in the
      failing heart and may be a biomarker not only for renal failure but also for
      heart failure. Because Lcn2/NGAL is thought to be induced by interleukin-1, it
      might be strongly induced in the presence of myocarditis. METHODS AND RESULTS:
      This study investigated the expression of Lcn2/NGAL in rat experimental
      autoimmune myocarditis (EAM) and in human myocarditis. In EAM hearts, the
      expression of Lcn2/NGAL was markedly increased (>100-fold at an early stage), and
      in human myocarditis it was also highly expressed compared with non-inflammatory
      failing hearts. Lcn2/NGAL expressing cells in hearts with EAM and human
      myocarditis were identified as cardiomyocytes, vascular wall cells, fibroblasts
      and neutrophils. Lcn2/NGAL in EAM rats was also expressed in the liver. Plasma
      Lcn2/NGAL levels abruptly increased at an early stage of EAM, and high levels
      were initially sustained during the inflammatory stage, then decreased with
      recovery. In contrast, levels of B-type natriuretic peptide increased only slowly
      as the disease progressed. CONCLUSIONS: Cardiomyocytes, vascular wall cells and
      fibroblasts in myocarditis strongly express Lcn2/NGAL via proinflammatory
      cytokines.

PMID- 20057161
TI  - Impact of blood pressure and other components of the metabolic syndrome on the
      development of cardiovascular disease.
AB  - BACKGROUND: Few prospective studies have explored blood pressure (BP) and other
      components of the metabolic syndrome (MetS) and their interaction in the
      development of cardiovascular diseases (CVD) in China. METHODS AND RESULTS: A
      prospective study of the prevention of multiple metabolic disorders and MetS in
      Jiangsu province, China: 3,598 subjects were followed for a median of 6.3 years.
      The Asian criterion of the National Cholesterol Education Program Adult Treatment
      Panel III was used to define the MetS. Independent risk of the MetS and its
      components on developing CVD was analyzed, but only BP was associated with CVD.
      Incidence and risk of CVD increased with the number of MetS components. A linear
      association was found between the risk of CVD, BP and the number of other
      components (trend, P<0.01). The adjusted relative risk of developing CVD was
      increased when BP and other components coexisted. However, the interaction of BP
      and other components of MetS was not significant (P>0.05). CONCLUSIONS: In
      Chinese, among the components of MetS BP was an independent risk factor for CVD.
      No significant interaction was found between BP and the other MetS components.

PMID- 20057162
TI  - Endocrine traits of polycystic ovary syndrome in prenatally androgenized female
      Sprague-Dawley rats.
AB  - Although hyperandrogenism is an important condition and is considered the
      possible pathogenesis behind polycystic ovary syndrome (PCOS), data supporting
      this is still scarce. We sought to determine whether or not prenatal androgen
      exposure leads to PCOS and the possible cellular mechanisms involved. To induce
      prenatal androgen exposure, pregnant rats were treated with daily subcutaneous
      injections of free testosterone (T) or dihydrotestosterone (DHT) from embryonic
      days 16 to 19, and their female offspring were studied as adults. The mRNA
      expression of the progesterone receptor (PR) in the preoptic area (POA)
      hypothalamus was higher in the experimental groups than in the control group
      after ovariectomy and stimulation with estradiol benzoate. The levels of T, P,
      leutinizing hormone (LH), and estradiol were higher in the experimental groups
      than in the control groups. The frequency and magnitude of LH secretion was
      increased in experimental rats as compared with the control group. The anogenital
      distance of the experimental groups was prolonged and the nipple number was lower
      than that of the control group. Almost all experimental rats had prolonged or
      irregular estrous cycles. The experimental groups had fewer corpus luteum and
      preovulatory follicles and more preantral follicles and antral follicles than the
      controls. Our findings are consistent with the hypothesis that excess androgen
      during the prenatal period may cause PCOS. Additionally, we show that
      hyperandrogenic interference in the release of preovulatory LH surges is mediated
      by the suppressive effects of androgens on PR expression in POA-hypothalamic
      tissue.

PMID- 20057163
TI  - Assessment of transcriptional responses of Bacillus subtilis cells to the
      antibiotic enduracidin, which interferes with cell wall synthesis, using a high
      density tiling chip.
AB  - The cell envelope is the target for many antibiotics. In Gram-positive bacteria,
      membrane alterations and dysfunction caused by antibiotics are sensed mainly by
      two classes of signal transduction systems: the ECF sigma factors and the two
      component signal transduction systems (TCSs). Enduracidin is an antibiotic that
      inhibits the transglycosylation step of peptidoglycan biosynthesis, and is an
      attractive target for further antibiotic development studies. We assessed
      transcriptional responses to enduracidin in Bacillus subtilis cells using a high
      density tiling chip, and compared the results with responses to bacitracin, which
      inhibits the lipid II cycle of peptidoglycan synthesis. We exploited the
      quantitative advantage of the tiling chip to introduce a new criterion, an
      increase in transcriptional level, in addition to the conventional induction
      ratio, in order to distinguish genes of biological significance from those with
      lower induction ratios. Our results indicate that introduction of the new
      criterion led to unambiguous identification of core transcriptional responses to
      antibiotics, with a reduction in the number of possible background genes,
      compared to previous results obtained using gene arrays. We identified 129 genes
      that were significantly upregulated by enduracidin and/or bacitracin. Notably, we
      found that inactivation of the LiaRS TCS, which was the system most strongly
      induced by the two antibiotics, resulted in increased sensitivity to enduracidin,
      probably through a failure to induce LiaIH proteins. We noted that 33 genes
      belonging to the SigM regulon were induced by both antibiotics. Consistent with
      stronger induction of the SigM regulon in enduracidin-treated cells, inactivation
      of sigM resulted in increased sensitivity to enduracidin. In addition, and for
      the first time, we found that the Spx regulon was induced in cells challenged by
      enduracidin and bacitracin, suggesting that thiol-oxidative stress occurred in
      cells treated with antibiotics. These findings contribute to further our
      understanding of the molecular nature of genetic systems involved in antibiotic
      resistance.

PMID- 20057164
TI  - Transcription factors of M-phase cyclin CLB2 in the yeast cell wall integrity
      checkpoint.
AB  - The cell wall integrity checkpoint coordinates cell wall synthesis and mitosis in
      the budding yeast, Saccharomyces cerevisiae. It has been reported that this
      checkpoint arrests the cell cycle at G2/M phase with repression of the M phase
      cyclin Clb2p at the transcriptional level, under perturbation of cell wall
      synthesis. We demonstrate that an override of this checkpoint with accumulation
      of CLB2 mRNA is induced when negative CLB2 transcription factors are deleted or
      when positive CLB2 transcription factors are overproduced in cell wall-defective
      cells. Our data imply that transcription factors for CLB2 are involved in the
      cell wall integrity checkpoint system and suggest that there are multiple
      regulation pathways of the checkpoint.

PMID- 20057165
TI  - Levels and patterns of DNA variation in two sympatric mangrove species,
      Rhizophora apiculata and R. mucronata from Thailand.
AB  - In mangrove species the past geomorphic changes in coastal regions and
      reproductive systems are important factors of their distribution and genetic
      structure of populations. However, very little is known about the levels of
      genetic variation of Rhiozophora species in Southeast Asia. In this study, we
      surveyed levels and patterns of genetic variation as well as population structure
      of two sympatric mangrove species, Rhizophora apiculata and R. mucronata in
      Thailand, using five nuclear genes and two cpDNA regions. In all investigated DNA
      regions, nucleotide variation within species was low, while nucleotide divergence
      between the two species was considerable. The nuclear genes evolved 10 times
      faster than the cpDNA regions. In both R. apiculata and R. mucronata, significant
      positive F(IS) values were found, indicating deviation from Hardy-Weinberg
      proportions and a deficiency of heterozygotes. In both species, we found
      significant genetic differentiation between populations. However, the pattern of
      population differentiation (F(ST)) of R. apiculata differed from that of R.
      mucronata. Our results suggest that the two investigated species have different
      demographic history, even though they are sympatric and have similar reproductive
      systems.

PMID- 20057166
TI  - Peripatric differentiation among adjacent marine lake and lagoon populations of a
      coastal fish, Sphaeramia orbicularis (Apogonidae, Perciformes, Teleostei).
AB  - The effect of geographical isolation on speciation, particularly within short
      geographical ranges, is poorly understood among marine organisms. Focusing on
      marine lakes of the Palau Islands, we investigated the effect of geographical
      isolation on Sphaeramia orbicularis, a coastal fish inhabiting marine lakes and
      lagoons. We collected a total of 157 individuals from three meromictic marine
      lakes and three lagoon sites, and analyzed the genetic diversity and
      differentiation of the populations based on complete sequences of the
      mitochondrial control region (824 bp). The analyses show that the genetic
      diversity of marine lake populations is much lower than that of lagoon
      populations. Moreover, a mismatch distribution analysis suggests that marine lake
      populations have experienced a decrease followed by a rapid expansion of their
      population size. These results reveal that marine lake populations have
      experienced severe founder and/or bottleneck events during the last thousand to
      tens of thousand years. Pairwise Phi(ST )values ranged from 0.531 to 0.848
      between marine lake and lagoon populations and from 0.429 to 0.870 among marine
      lake populations, indicating a high degree of genetic differentiation. We
      speculate that such peripatric differentiation between marine lake and lagoon
      populations was caused by a small number of individuals colonizing the lakes from
      the lagoon (founder event) followed by repetitive bottleneck events, such as
      those generated by the El Nino-Southern Oscillation (ENSO). So far, such high
      genetic divergences in extremely short geographical ranges (approximately 150-250
      m) have scarcely been reported for marine organisms. We suggest that the marine
      lake is one of the good model of geographical isolation in marine organisms and
      each marine lake population is in the early stages of speciation.

PMID- 20057167
TI  - Tandem duplication of mitochondrial DNA in the black-faced spoonbill, Platalea
      minor.
AB  - Mitochondrial (mt) heteroplasmy in the control region (CR) of the black-faced
      spoonbill was investigated using LA-PCR. To avoid amplification of
      transpositioned nuclear genome fragment from mtDNA (numt), PCR product of the
      almost-complete mitochondrial genome was amplified using primers designed to
      anneal on the COIII gene. Then nested LA-PCR product was amplified between the
      cyt b and 12S rRNA genes using the almost-complete mitochondrial genome PCR
      product as a template. Nucleotide sequencing revealed tandem duplication composed
      of two units. The first contains cyt b-1, tRNA(Thr)-1, tRNA(Pro)-1, ND6-1,
      tRNA(Glu)-1 and CR1, and the second consists of cyt b-2, tRNA(Thr)-2, tRNA(Pro)
      2, ND6-2, tRNA(Glu)-2 and CR2, followed by tRNA(Phe) and 12S rRNA. The duplicated
      cyt b-2 sequence coincided with 499 bp at the 3' end of cyt b-1. With the
      exception of the CR, the other genes in the duplicated sequence were identical to
      the original corresponding gene. Even though both CR1 and CR2 contain functional
      blocks, such as a poly-C site, a goose hairpin and a TAS structure in Domain I,
      the 3' end of CR1 was followed by a 112 bp sequence (non-coding region) that was
      not found in CR2 or in sequence homology analysis of similar genes. Meanwhile,
      CR2 ended in a complicated repeat sequence. The 5' franking region in the Domain
      I (Region A) and the 3' franking region in the Domain I (Region B) of the two CRs
      evolve in quite different manners: Region A was highly variable between CR1 and
      CR2 in the same individuals, while Region B was almost identical between them,
      which indicates concerted evolution.

PMID- 20057168
TI  - A genomic scanning using AFLP to detect candidate loci under selection in the
      finless porpoise (Neophocaena phocaenoides).
AB  - Identifying loci under natural selection from genomic surveys is of great
      interest in different research areas, stimulated by the increasing ease with
      large numbers of markers to gain a genome-wide perspective on differentiation. In
      this study, we searched for the genetic signatures of selection by screening 114
      amplified fragment length polymorphism (AFLP) markers in three finless porpoise
      populations inhabiting contrasting natural environments (freshwater and marine
      habitat). Comparing among three populations, four AFLP loci exhibited F(ST)
      values higher than 0.975 quantile which might be inferred to be under divergent
      selection and two loci fell below the 0.025 quantile which might be affected by
      balancing selection. Although these loci were not supported with statistical
      significance in false discovery rate (FDR) analysis, the present study
      illustrated the potential of genome-wide surveys to identify specific genome
      regions or genes associated with freshwater adaptation of the finless porpoise.

PMID- 20057169
TI  - A new simple method to introduce marker-free deletions in the Bacillus subtilis
      genome.
AB  - A genetic tool to introduce marker-free deletions is essential for multiple
      manipulations of genomes. We report a simple and efficient method to create
      marker-free deletion mutants of Bacillus subtilis through transformation with
      recombinant PCR products, using the Escherichia coli mazF gene encoding an
      endoribonuclease that cleaves free mRNAs as a counter-selection tool. Our method
      will be applicable to any bacterium in which introduction of the mazF cassette
      into the genome by double crossover homologous recombination is possible.

PMID- 20057170
TI  - TGF-beta1 up-regulates expression of ABCA1, ABCG1 and SR-BI through liver X
      receptor alpha signaling pathway in THP-1 macrophage-derived foam cells.
AB  - AIM: High density lipoprotein (HDL) and its apolipoproteins can promote
      cholesterol efflux from macrophage foam cells via the ATP-binding cassette
      transporter A1 (ABCA1), ABCG1, and scavenger receptor class B type I (SR-BI).
      Liver X receptors (LXRs) operate as cholesterol sensors which may protect from
      cholesterol overload by stimulating cholesterol efflux from cells to HDL through
      ABCA1, ABCG1 and SR-BI. The regulation of ABCA1, ABCG1 and SR-BI expression by
      cytokines present within the microenvironment of the atheroma may play an
      important role in determining the impact of reverse cholesterol transport on the
      atherosclerotic lesion. In the current study, we examined the effect of
      transforming growth factor-beta1 (TGF-beta1) on expressions of ABCA1, ABCG1 and
      SR-BI and explored the role of LXR alpha in the regulation of ABCA1, ABCG1 and SR
      BI in THP-1 macrophage-derived foam cells. METHODS AND RESULTS: TGF-beta1
      significantly increased expressions of ABCA1, ABCG1 and SR-BI at both
      transcriptional and translational levels in a dose-dependent and time-dependent
      manner. Cellular cholesterol content was decreased while cholesterol efflux was
      increased by TGF-beta1 treatment. Moreover, LXR alpha was up-regulated by TGF
      beta1 treatment. In addition, LXR alpha small interfering RNA completely
      abolished the promotion effect induced by TGF-beta1. CONCLUSION: These results
      provide evidence that TGF-beta1 up-regulates expressions of ABCA1, ABCG1 and SR
      BI through the LXR alpha pathway in THP-1 macrophage-derived foam cells.

PMID- 20057171
TI  - BMI specific waist circumference for detecting clusters of cardiovascular risk
      factors in a Japanese population.
AB  - AIM: The purpose of the study was to determine the sensitive cutoff values of
      waist circumference (WC) in relation to the body mass index (BMI) for detecting
      the clustering of cardiovascular risk factors (CCRF) in Japanese men and women.
      METHODS: The study population included 2,476 male and female residents who
      participated in a ward health examination in Tokyo, Japan. The CCRF were defined
      according to the Japanese Committee of the Criteria for Metabolic Syndrome.
      Receiver Operating Characteristics (ROC) analysis was conducted within each BMI
      category. RESULTS: The percentage of study participants in the normal BMI
      category was around 70% for both men and women. The sensitive cutoff values for
      the largest WC with at least 80% sensitivity were 81 cm for normal and 89 cm for
      overweight men. The corresponding values for women were 79 cm and 86 cm,
      respectively. The WC with maximized sensitivity plus specificity was 80 cm for
      normal and 89 cm for overweight men, and the sensitivity was 88.7% and 83.0%,
      respectively. The corresponding values for women were 78 and 94 cm, respectively,
      and the sensitivity was 91.5% and 57.6%, respectively. CONCLUSIONS: For the early
      detection and management of clusters of cardiovascular risk factors, we concluded
      that a BMI-specific WC cutoff value of 80 cm for normal weight in both men and
      women and 89 cm for overweight men and 86 cm for overweight women should be
      discriminate cutoff values.

PMID- 20057172
TI  - Prehypertension among middle-aged and elderly people in Taiwan: a five-year
      follow-up.
AB  - AIM: To evaluate the prevalence of prehypertension among middle-aged and elderly
      people in Taiwan and to explore the evolutionary changes of blood pressure in 5
      year follow-up period. METHODS: In 2000, people aged over 40 participating in
      annual health examinations at local health stations in I-Lan County were invited
      to join the study. Past medical histories were reviewed, physical examinations
      and serial laboratory tests were performed for participants. All participants
      were followed in 2005 by a medical record review, telephone survey or personal
      visit. Subjects with prehypertension were sorted for further analysis. RESULTS:
      Overall, 1053 people (mean age=64.4+/-11.4 years, 44.4% males) were enrolled in
      the primary cohort. The prevalence of hypertension and prehypertension was 40.4%
      and 35.8%, respectively. In 2005, 677 subjects (mean age: 68.8+/-10.4 years,
      42.5% males) were successfully followed, which revealed a significant increase of
      systolic blood pressure (3.7+/-16.8 mmHg, p<0.001), but not diastolic blood
      pressure (0.3+/-11.5 mmHg, p=0.758) in prehypertensive subjects; however, both
      systolic blood pressure (14.3+/-17.4 mmHg, p<0.001) and diastolic blood pressure
      (7.7+/-13.3 mmHg, p<0.001) were significantly increased among normotensive
      subjects. The cumulative incidence of prehypertensive subjects becoming
      hypertensive was 31.3%, and those who became hypertensive were significantly
      older (65.3+/-8.6 vs. 62.2+/-12.3 years, p=0.024), having higher pulse pressure
      in 2000 (49.6+/-10.6 vs. 45.1+/-11.6 mmHg, p=0.001), serum total cholesterol
      (214.3+/-31.7 vs. 204.0+/-37.2 mg/dL, p=0.020) and low-density lipoprotein
      cholesterol (141.7+/-29.2 vs. 132.7+/-34.7 mg/dL, p=0.042). CONCLUSIONS: The
      prevalence of prehypertension among older Taiwanese was 35.8% and the 5-year
      cumulative incidence of hypertension from prehypertension was 31.3%. Older
      prehypertensive subjects with higher pulse pressure, higher serum total
      cholesterol and higher low-density lipoprotein-cholesterol were more likely to
      become hypertensive within 5 years.

PMID- 20057173
TI  - Effects of local and whole body irradiation on the appearance of osteoblasts
      during wound healing in tooth extraction sockets in rats.
AB  - Irradiation before tooth extraction delays wound healing in the alveolar socket.
      This study examined the influences of local and whole body irradiation before
      tooth extraction on appearance of osteoblasts in the alveolar bone of rat
      maxillary first molars because bone formation is observed at the initial phase of
      wound healing. Several osteoblasts were generated 3 days after tooth extraction,
      and the number of cells increased day by day. Morphological studies showed there
      were little differences between local irradiation and non-irradiated controls. In
      contrast, the extraction wound in the whole body irradiation group showed delayed
      healing, and there was poor granulation tissue and very few osteoblasts at the
      bottom of the socket. An ultrastructural study showed that the osteoblasts in the
      extraction socket of whole body irradiation rats were smaller, and had poorly
      developed organelles. Injection of bone marrow cells to whole body-irradiated
      animals immediately after tooth extraction partially restored the number of
      osteoblasts. New periosteal bone formations outside of sockets showed little
      delay in the whole body irradiation group. These findings suggest that bone
      formation in the wound healing of extraction socket requires bone marrow cells
      from hematopoietic organs such as the bone marrow as well as local sources around
      the alveolar socket, during the initial phase of wound healing.

PMID- 20057175
TI  - Subcutaneous Leiomyosarcoma in a Common Squirrel Monkey (Saimiri sciureus).
AB  - Leiomyosarcoma in soft tissue has only been reported in humans or animals. We
      performed pathological examination of a 3-years-old male squirrel monkey which
      had a large mass in the right axilla. The mass in the right axilla was surgically
      resected but it soon reoccurred. This tumor was diagnosed as a leiomyosarcoma
      based on histopathology and immunohistochemistry using the expression of alpha
      smooth muscle actin and desmin. Leiomyosarcoma in squirrel monkey has been
      reported in one case, there was no reoccurrence or metastasis. Most of the
      reported tumors in nonhuman primates have occurred in aged monkeys. This case was
      a rare tumor considering the young age of the animal.

PMID- 20057174
TI  - The effects of x-irradiation on ex vivo expansion of cryopreserved human
      hematopoietic stem/progenitor cells.
AB  - In our previous study (Life Sciences 84: 598, 2009), we demonstrated that
      placental/umbilical cord blood-derived mesenchymal stem cell-like stromal cells
      have the effect to support the regeneration of freshly prepared X-irradiated
      hematopoietic stem/progenitor cells (HSPCs). Generally, HSPCs are supplied from
      companies, institutions, and cell banks that cryopreserve them for clinical and
      experimental use. In this study, the influence of cryopreservation on the
      responses of HSPCs to irradiation and co-culture with stromal cells is assessed.
      After cryopreservation with the optimal procedure, 2 Gy-irradiated HSPCs were
      cultured with or without stromal cells supplemented with combination of
      interleukin-3, stem cell factor, and thrombopoietin. The population of relatively
      immature CD34(+)/CD38(-) cells in cryopreserved cells was significantly higher
      than in fresh cells prior to cryopreservation; furthermore, the hematopoietic
      progenitor populations of CD34(+)/CD45RA(+) cells and CD34(+)/CD117(+) cells in
      cryopreserved cells were significantly lower than that in fresh cells. However,
      the rate of expansion in the cryopreserved HSPCs was lower than in the fresh
      HSPCs. In the culture of cryopreserved cells irradiated with 2 Gy, the growth
      rates of CD34(+) cells, CD34(+)/CD38(-) cells, and hematopoietic progenitors were
      greater than growth rates of their counterparts in the culture of fresh cells.
      Surprisingly, the effect to support the hematopoiesis in co-culture with stromal
      cells was never observed in the X-irradiated HSPCs after cryopreservation. The
      present results demonstrated that cryopreserving process increased the rate of
      immature and radio-resistant HSPCs but decreased the effects to support the
      hematopoiesis by stromal cells, thus suggesting that cryopreservation changes the
      character of HSPCs.

PMID- 20057176
TI  - Corticosterone synthesis inhibitor-induced decrease in the age-dependant
      expression of nitric oxide synthase 3 in the preterm ductus arteriosus of rats.
AB  - Previous studies have shown that the dilating effect of nitric oxide (NO) on the
      fetal ductus arteriosus (DA) is age dependent and more marked in the premature
      stages in rats, but the factors that mediate this effect are poorly understood.
      The purpose of this study is to determine the changes in the expression of NO
      synthase (NOS) mRNA in the fetal DA and to examine the effect of an 11-beta
      hydroxylase inhibitor of corticosterone synthesis, namely, metyrapone, on NOS
      expression. NOS 3 mRNA expression was observed in 17.5-day-old rat fetuses;
      thereafter, its level significantly increased and reached its peak on day 19.5
      and then decreased until the end of the gestation period (day 21.5). To inhibit
      corticosterone synthesis, a constant infusion of metyrapone was administered to
      rats; this significantly decreased the fetal plasma corticosterone concentration
      as well as NOS 3 mRNA expression in the DA in a time-dependent manner. These
      results indicate that NO is generated by NOS 3 in the DA and that the age
      dependant expression of NOS 3 in the premature DA is attributable to
      corticosterone-associated activity.

PMID- 20057177
TI  - A case control study of Bovine Viral Diarrhea Virus (BVDV) Persistent Infection
      (PI) in Betsukai, Hokkaido, Japan.
AB  - The Betsukai town office implemented bovine viral diarrhea virus (BVDV)
      preventive activities (i.e., vaccination and surveillance) in 2006. Using bulk
      tank milk screening followed by individual blood tests using a Reverse
      Transcription-Polymerase Chain Reaction (RT-PCR) method, persistent infection
      (PI) cattle were detected and eliminated from the population. Based on data for
      PI cattle detected between 2006 and 2007, we conducted a case control study to
      find risk factors associated with the presence of PI cattle. Significantly
      associated farm level factors for increasing risk of producing PI cattle include;
      1) no recent purchase of cattle (between 2004 and 2007) and 2) no prevention of
      people/animals entering the premises. This study suggests that not only vertical
      transmission from dam to calf but also indirect contact with people and animals
      play an important role in transmitting BVDV infection and subsequent production
      of PI animals.

PMID- 20057178
TI  - [Professional activity of women in medicine].

PMID- 20057179
TI  - [Anti-viral treatment for liver cirrhosis].

PMID- 20057180
TI  - [Current management for hepatic encephalopathy in cirrhotic patients].

PMID- 20057181
TI  - [Current status of liver transplantation for liver cirrhosis and unsolved
      problem].

PMID- 20057182
TI  - [Recent topics on management of liver cirrhosis: discussion].

PMID- 20057183
TI  - [The usefulness and limitations of the new Japanese criteria for severity
      assessment in acute pancreatitis].
AB  - New Japanese criteria for severity assessment in acute pancreatitis were
      introduced in October 2008. The new criteria are simpler than the previous ones,
      and are also expected to be more useful for the severity assessment. We
      retrospectively analyzed the clinical factors in our patients to predict
      prognosis, and evaluated the usefulness and limitations of the new criteria.
      There were few missing data in the new criteria compared with the previous
      criteria. The areas under the receiver operating characteristic (ROC) curves for
      mortality prediction were 0.870 for the new criteria and 0.884 for the previous
      criteria. However, there were more patients whose disease severity on admission
      were underestimated using the new criteria and who finally progressed to worse
      stages including death. This evidence strongly suggests the lower sensitivity of
      the new criteria in mortality prediction. Repeated assessment of severity after
      admission will be indispensable in the proper treatment of patients with acute
      pancreatitis.

PMID- 20057184
TI  - [Collision tumor of a carcinoid and carcinoma in the rectum].
AB  - A man in his seventies visited our hospital due to positive a fecal occult blood
      test. Colonoscopy showed a submucosal tumor in the rectum covered with reddish
      and irregular mucosa. Pathological examination of the biopsy specimen revealed
      well differentiated adenocarcinoma. The tumor was resected, and pathological
      examination showed carcinoid and adenocarcinoma components coexisting and mixed
      with each other. Because a previous colonoscopy had shown a submucosal tumor with
      a smooth surface, this case was diagnosed as a collision tumor of adenocarcinoma
      which developed on a carcinoid.

PMID- 20057185
TI  - [Three cases of serious abdominal tuberculosis associated with pulmonary
      tuberculosis].
AB  - Case 1) A 21-year-old Thai woman, and Case 2) a 22-year-old Indonesian woman,
      were each given a diagnosis of pulmonary tuberculosis. Immediately after starting
      medication, peritonitis symptoms appeared. Colonoscopies detected multiple rings
      and zonal ulcers. Abdominal tuberculosis was diagnosed, and anti-tubercular
      therapy was effective. Case 3) A 23-year-old man was given a diagnosis of
      pulmonary tuberculosis. The day after starting anti-tubercular therapy, he
      complained of abdominal pain that increased with muscular defense. He was given a
      diagnosis of perforation of the digestive tract, underwent emergency surgery, and
      recovered. Pathological examinations revealed granuloma with caseous necrosis and
      Mycobacterium tuberculosis. Physicians should be aware that tuberculosis can be a
      potential source of acute abdomen in young adults who do not take proper care of
      their health.

PMID- 20057186
TI  - [A case of adult intussusceptions with multiple colon cancer].
AB  - A 64-year-old woman visited our outpatient clinic because of bloody stools and
      abdominal fullness. Digital rectal examination revealed a 6 x 4-cm oval mass.
      Abdominal CT scans demonstrated a concentric, multilayered structure in the
      rectum. Colonoscopy showed segments of the bowel were dark-purplish, and
      intussusception. Deeper insertion of the colonoscope through the lumen revealed a
      type 1 lesion. Under a diagnosis of sigmoid colon cancer with intrarectal
      intussusception, emergency surgery was performed. The resected specimen showed a
      type 1 advanced cancer and two early cancers at the base of the intussuscepted
      colon, all of which appear to have contributed to the intussusception.

PMID- 20057187
TI  - [A case of neuroendocrine carcinoma which originated in duodenal bulb].
AB  - A 95-year-old woman who presented with ischemic heart disease was admitted due to
      a sensation of chest compression. Endoscopy was performed due to anemia which
      showed an irregular ulcerative lesion in the duodenal bulb which a biopsy
      revealed to be high-grade neuroendocrine carcinoma. Distant metastasis was found
      and the patient died from the original disease 3 months after the first medical
      examination. The result of autopsy was neuroendocrine carcinoma of duodenum and
      invasion and metastases to multiple organs. We report a case of neuroendocrine
      carcinoma originating from the duodenum excluding the papilla which is extremely
      rare in Japan.

PMID- 20057188
TI  - [Primary diaphragmatic schwannoma which needed to be distinguished from a liver
      tumor].
AB  - A 55-year-old woman was admitted because of a tumor located in the ventral region
      of S4 of the liver, just beneath the diaphragm. A CT scan revealed the round
      tumor to be delineated as a 33 mm in size, with an outer capsule. The tumor was
      visualized as concentric circles which presented high-, low-, and high- signal
      patterns on T2-weighted MRI. It also presented a triphasic pattern in which the
      border and the central part were not contrasted as a low signal pattern, while
      the middle part was contrasted as a high signal pattern by T1-weighted enhanced
      imaging with Gd-DTPA. Angiography revealed that the tumor did not originate from
      the liver but from the diaphragm, so it was surgically resected as a primary
      diaphragmatic tumor. We report a schwannoma which originated from the diaphragm,
      that showed characteristic imaging findings and required to be distinguished from
      a liver tumor.

PMID- 20057189
TI  - [Hyperplastic hepatic nodules in a case of idiopathic portal hypertension:
      changes in imaging findings during a 6-year follow-up].
AB  - A 22-year-old man had been given a diagnosis of idiopathic portal hypertension in
      childhood. In June 2001, a hepatic nodule which gradually increased in size over
      the next 2 years, was detected in the left hepatic lobe. In February 2003, a left
      lateral segmentectomy was performed. Histological examination of the nodules
      suggested focal nodular hyperplasia (FNH)-like hyperplasia. Computerized
      tomography performed 2 years later showed other hepatic nodules, and a liver
      biopsy was performed. Histopathological examination conducted at this time also
      suggested FNH-like hyperplasia. Owing to the substantial enlargement of the
      nodules and frequent recurrence, it can be difficult to distinguish between
      benign and malignant lesions.

PMID- 20057190
TI  - A case of distal bile duct cancer with extensive intraepithelial spread diagnosed
      preoperatively by peroral cholangioscopy combined with narrow band imaging.
AB  - A 75-year-old woman with jaundice was given a diagnosis of bile duct cancer using
      several imaging modalities. The proximal and middle bile ducts were evaluated as
      normal by multidetector-row CT and intraductal ultrasonography. However, peroral
      cholangioscopy (POCS) with narrow band imaging (NBI) clearly revealed the
      intraepithelial extent of the bile duct cancer from the distal bile duct to the
      hilar bile duct, which was confirmed by histological examination of the resected
      specimen. POCS combined with NBI is expected to be useful for determining the
      resection margin in bile duct cancer cases.

PMID- 20057191
TI  - [A case of splenic abscess with successful transcutaneous drainage].

PMID- 20057192
TI  - Back to medieval witch burning.

PMID- 20057193
TI  - Bariatric surgery for obese adolescents - 'make assurance doubly sure'.

PMID- 20057194
TI  - A simple dietary intervention in the school setting decreased incidence of
      overweight in children.
AB  - OBJECTIVE: The study analyzed the effect of a combined environmental and
      educational intervention solely promoting water consumption on the incidence of
      overweight among school children. METHODS: 2,950 second and third graders of 32
      elementary schools in socially deprived neighborhoods of two German cities
      participated in a randomized controlled intervention trial (August 2006-June
      2007). In intervention schools (N = 17), water fountains were installed, each
      child received a water bottle, and teachers performed classroom lessons to
      promote water consumption. Control schools (N = 15) did not receive any
      intervention. Body heights and weights were measured at baseline and follow-up to
      assess the incidence and remission of overweight and obesity during follow-up.
      The water flow of the fountains was measured regularly during follow-up.
      Children's beverage consumption was self-reported in 24-hour recall
      questionnaires before and after intervention. RESULTS: After the intervention,
      the incidence of overweight was significantly lower in the intervention group
      (3.8%) than in the control group (6.0%, p = 0.018). Remission of overweight and
      obesity did not differ between the groups. Measured water flow of the fountains
      indicated a sustained use. CONCLUSION: A simple dietary intervention with the
      sole focus on the promotion of drinking water effectively reduced the incidence
      of overweight among school children.

PMID- 20057195
TI  - Effects of a combined inpatient-outpatient treatment of obese children and
      adolescents.
AB  - BACKGROUND: The program The combined DAK therapy for obesity in children and
      adolescents' funded and conducted by the Deutsche Angestellten-Krankenkasse
      (DAK), a German health insurance company, commenced in 2003. The treatment
      program lasts for 1 year and comprises of 2 phases: an initial inpatient therapy
      for 6 weeks followed by a home-based outpatient treatment of the overweight
      children, adolescents, and their families for 10.5 months. The therapy complies
      with the guidelines of the German Working Group of Obesity in Childhood and
      Adolescence (AGA). PARTICIPANTS AND METHODS: In this study, 162 obese children
      and adolescents were compared with a control group of 75 obese subjects recruited
      from the waiting list for the program. The aim was to analyze whether the changes
      in weight, eating behavior, and physical fitness during the therapy period are a
      result of the therapy itself or whether they are attributable to external
      effects. Body weight, height, and physical fitness were assessed through direct
      measurements while behavior and quality of life were assessed using self-report
      questionnaires. The development of body weight was evaluated using the BMI-SDS
      which is a measure of how many standard deviations an individual BMI is above or
      below the age- and gender-specific mean. RESULTS: Within the observation period
      the BMISDS decreased significantly by 0.36 +/- 0.34 in the intervention group,
      whereas no changes of BMI-SDS were observed in the control group (0.04 +/- 0.17).
      The study revealed significant, positive treatment effects in exploratory
      analyses with regard to weight loss, behavior changes, physical fitness, and
      development of quality of life as a result of the therapy. These effects were not
      seen in the control group. CONCLUSION: We conclude that these positive
      developments are a result of the treatment program.

PMID- 20057196
TI  - Adiposity measures as indicators of metabolic risk factors in adolescents.
AB  - AIM: To examine the relation between adiposity assessment methods (percentage
      body fat (%BF), BMI, and waist circumference (WC)) and individual metabolic risk
      factors (f-insulin, HDL cholesterol, triglycerides) and a combined measure of
      metabolic risk. METHODS: Crosssectional study of 300 males (BMI 20.8 +/- 3.0
      kg/m(2)) and females (BMI 21.3 +/- 2.9 kg/m(2)) 17 years of age. F-insulin and
      components of the metabolic syndrome defined by the International Diabetes
      Federation (IDF) were used as metabolic risk indicators, with samples stratified
      into BMI, %BF, and WC groups, respectively. Diagnostic accuracy was expressed as
      the area under the ROC curve (AUC). RESULTS: In males, diagnostic accuracy for
      HDL and f-insulin was poor to fair for BMI (AUC 0.70, p = 0.001; 0.60, p = 0.22),
      WC (0.68, p = 0.003; 0.63, p = 0.11), and %BF (0.65, p = 0.009; 0.66, p = 0.04).
      The diagnostic accuracy for triglycerides was greater for all three measures (BMI
      0.92, WC 0.95, %BF 0.87; all p < 0.001). For females, neither test performed
      better than chance for f-insulin and HDL, and only %BF performed better than
      chance for triglycerides (0.65, p = 0.08). All three measures exhibited higher
      accuracy for presence of > or =2 metabolic risk factors (AUCs 0.76-0.91, p <
      0.001) in both sexes. CONCLUSION: %BF was not superior to BMI and WC for
      detecting metabolic risk in the general adolescent population.

PMID- 20057197
TI  - Longitudinal modelling of body mass index from birth to 14 years.
AB  - BACKGROUND: To examine the tracking of BMI from birth to age 14 years.
      PARTICIPANTS AND METHODS: Linear mixed model (LMM) analysis was used to model the
      trajectories of BMI (n = 1,403). Adiposity rebound was investigated for a subset
      of individuals (n = 173). RESULTS: Adolescents who were overweight or obese at 14
      years followed a different BMI trajectory from birth compared to those of normal
      weight. There was a difference between weight status groups for the timing of
      adiposity rebound (p < 0.001) and BMI at nadir (p < 0.001). The LMM depicted a
      significant difference in rate of change of BMI over time for males and females
      (p < 0.001), with female BMI increasing at a faster rate, and for weight status
      groups (p < 0.005), with the obese cohort having the faster increase in BMI over
      time. BMI at birth was significantly lower for the normal weight cohort compared
      to the overweight (p = 0.029) and obese (p = 0.019) cohorts. CONCLUSION: This
      study introduces a powerful analytic tool, LMM, to model BMI and shows that
      weight status at 14 years is the result of a distinct path in earlier years.
      Compared to their normal weight peers, overweight and obese adolescents
      experience an earlier adiposity rebound, with a higher BMI at rebound.

PMID- 20057198
TI  - The impact of target weight and gender on perceptions of likeability, personality
      attributes, and functional impairment.
AB  - BACKGROUND: Bias against individuals who are overweight is well documented.
      However, little is known about biased perceptions of men and women at varying
      specified degrees of overweight. METHODS: Men and women (N = 308) rated male and
      female figures (low normal weight, overweight, obese, extremely obese) on
      measures of dislike, personality characteristics, and functional limitations.
      RESULTS: Little or no bias was observed against overweight figures (BMI
      approximately 25 kg/m(2)); however, strong bias was observed against obese and
      extremely obese figures. Men's ratings of extremely obese females were more
      negative than those of comparable males. However, for other weight categories,
      participants evidenced similar or greater weight bias against overweight and
      obese men than against female targets of corresponding weight. Furthermore, male
      participants tended to perceive heavier females as having more functional
      deficits and disliked them somewhat more than female participants. CONCLUSION: By
      using targets of known BMI categories, the current study enhances our
      understanding of who is likely to be impacted by weight bias. As individuals with
      a BMI < 30 kg/m(2) are typically not the targets of weight-related bias, research
      and efforts regarding weight-related bias should focus more specifically on those
      individuals who are obese or extremely obese.

PMID- 20057199
TI  - Cardiorespiratory fitness and components of the metabolic syndrome in sedentary
      men.
AB  - OBJECTIVE: To investigate the relationships between fitness and components of the
      metabolic syndrome in sedentary men. SUBJECTS AND METHODS: 39 subjects (34-53
      years) were evaluated for fitness (VO(2max)) and anthropometric, metabolic, and
      skeletal muscle phenotypes. VO(2max) was assessed on a bicycle ergometer whereas
      other variables were obtained from an oral glucose tolerance test (OGTT),
      hydrostatic weighing, and a muscle biopsy. RESULTS: Pearson and partial
      correlations adjusted for fat mass (FM), waist circumference (WC), muscle enzyme
      activities (citrate synthase (CS), cytochrome c oxidase (COX)), and capillary
      density were used to investigate the independent relationships be tween
      variables. Negative correlations between VO(2max) and WC as well as blood
      pressure and OGTT test were observed. When adjusted for FM, correlations remained
      between VO(2max) and WC (r = -0.46, p < 0.01) and systolic blood pressure (r = 
      0.35, p < 0.05). When adjusted for WC and CS activity, all correlations were lost
      except for high-sensitivity C-reactive protein (hs-CRP) (r = -0.34, p < 0.05)
      which remained when adjusted for CS activity. Adjustment for COX activity failed
      to remove correlations with hs-CRP (r = -0.36, p < 0.05), age (r = 0.34, p <
      0.05), WC (r = -0.35, p < 0.05), and blood pressure. Negative correlations
      persisted when fitness was adjusted for the mean number of capillaries.
      CONCLUSION: The effects of fitness on components of the metabolic syndrome in
      sedentary men are explained by abdominal obesity and muscle phenotypes.

PMID- 20057200
TI  - Mechanisms of weight loss after gastric bypass and gastric banding.
AB  - The obesity epidemic is a major health problem that is associated with increased
      morbidity and mortality. Gastrointestinal hormones have been increasingly
      understood to be an important element in appetite regulation. Several
      gastrointestinal hormones can contribute to obesity by modulating the activity of
      the gut-brain axis. Bariatric surgery is currently the most effective therapy for
      significant and sustained weight loss in morbidly obese patients. Understanding
      how gut hormones are altered by bariatric procedures has contributed to our
      understanding of the mechanisms of appetite. In this review, we address several
      gastrointestinal hormones that are associated with obesity and consider how their
      levels are altered after bariatric surgery. The review also addresses specific
      effects of different gut hormones on appetite, hunger, and energy balance.

PMID- 20057201
TI  - Sarcoidosis after adjustable silicone gastric banding - a report of two cases in
      Germany.
AB  - We report 2 patients who developed sarcoidosis after the implantation of
      adjustable silicone gastric banding (GB) in Germany. Before implantation, no
      pulmonary diseases were evident in the medical history of either patient. The 1st
      patient suffered sarcoidosis 12 months after GB. He has been treated at a
      hospital specialising in pulmonary diseases. Because of the treatment with
      corticoids, the patient has regained weight after the initial weight reduction.
      The 2nd patient developed signs of pulmonary infection on the 7th postoperative
      day (after GB). Pulmonary sarcoidosis was diagnosed 4 months later after
      consultation with a pulmonologist.

PMID- 20057202
TI  - Notes from the editor-in-chief. Are our healthcare investments worthwhile?

PMID- 20057203
TI  - Getting what we pay for? The value-for-money challenge.
AB  - In 2008, Canada spent $172 billion on healthcare, more than $5,000 for every man,
      woman and child in the country. Canada has one of the longer life expectancies in
      the Organisation for Economic Co-operation and Development and relatively low
      (and declining) amenable mortality rates. This suggests that the healthcare
      system is having some positive effect; but how well do we know what is "right"
      and what needs improvement? What do we get for the money we spend on healthcare?
      This paper proposes that there are some basic issues to address before these
      value-for-money questions can be answered. What do we value, or what do we want
      to achieve with our healthcare spending? Are we using inputs such as human
      resources well to provide services? Are we using services well to promote health?
      How would we know? The paper ends with a series of challenges to healthcare
      managers and decision-makers: to re-establish a broad information strategy, to
      include research as an integral part of healthcare delivery, to develop new data
      that can tell us something about outcomes of care and to articulate more formally
      objectives for the healthcare system.

PMID- 20057204
TI  - Contributing to the value-for-money challenge.
AB  - McGrail, Zierler and Ip do an excellent job of analyzing the complex issues
      surrounding the value-for-money challenge in healthcare. In response to their
      call for a new perspective, the following observations are made. Many questions
      can be asked to help articulate values. More will be accomplished in the short
      and medium term by focusing on the simpler questions. Some questions about value
      will never have an absolute answer with complete agreement. Furthermore, what is
      valued in healthcare tends to be clouded by what is rewarded in healthcare.
      Although the authors call for reviving the notion of building a pan-Canadian
      health information strategy, there are excellent examples of provincial success
      stories on which to build (e.g., Ontario's Wait Times Information System).
      Research and evaluation will not add value unless they are closely linked to the
      knowledge needs of decision- and policy makers. In reply to the authors' call to
      stop treating information technology as optional and demand that anyone paid with
      public funds report on the use of those funds, it should be recognized that
      information technology is the enabler that everyone should use. What we need to
      stop treating as optional is accountability and appropriateness for the use of
      funds.

PMID- 20057205
TI  - Focus on healthcare: a wider lens.
AB  - Achieving greater healthcare efficiency requires a much better understanding of
      the relationships and processes that occur between the inputs and outputs of the
      system. It also requires a broadening of the lens to include the determinants of
      health. The answers to many of the questions posed by the authors of the lead
      article lie in research, a key area of needed investment if Canada is going to
      respond to the value-for-money challenge.

PMID- 20057206
TI  - Notes on value for money in healthcare.
AB  - This commentary addresses three chief issues. First, it suggests that value in
      health is an inadequate goal in the absence of other important criteria for
      assessing healthcare systems, such as responsiveness and fairness. Second, it
      observes that the measurement of health outcomes necessary for obtaining value in
      health creates a danger of unintended consequences, as the healthcare providers
      being measured may try to avoid treating "difficult" patients. Third, it suggests
      that new mechanisms need to be employed to better align the interests of
      providers with those of patients.

PMID- 20057207
TI  - Value for money: putting the patient first.
AB  - Canadians spend more on healthcare than people in most other countries. We are
      fifth in the OECD in terms of health spending per capita, and eighth out of 28
      countries in terms of health spending as a percentage of GDP. Given these facts,
      it is appropriate to discuss the issue of value for money in healthcare. In their
      paper, McGrail et al. present four challenges to improving value for money in
      Canadian healthcare: a lack of analysis of the hospital sector; the need to learn
      from rate variation analysis; the slow uptake of the electronic health record
      (EHR); and the need to measure health outcomes. Our paper addresses each of these
      points, but also proposes that a broader outlook is needed to come to grips with
      this question. It is essential to go beyond supply-side cost control, and also
      take into account the needs of the patient. Moreover, we need to look beyond our
      borders to learn how other countries have been able to evolve universal publicly
      funded health systems without long waiting times.

PMID- 20057208
TI  - Adding value while saving dollars: unleashing the potential of a national,
      integrated approach to home and community care.
AB  - This commentary by Victorian Order of Nurses Canada, written in response to
      "Getting What We Pay For? The Value-for-Money Challenge," by McGrail, Zierler and
      Ip, answers four key questions about Canada's home and community care sector: (1)
      What are our objectives? (2) Where do we achieve good value now? (3) Where and
      why are we failing? and (4) What will help us do better? We conclude that
      although the home and community care sector offers great promise in meeting the
      evolving health and social needs of Canadians, it is not living up to its
      potential. We propose the development of a national, integrated approach to home
      and community care to help Canadians remain healthy and independent in their
      homes. This would represent a wise financial investment for governments and would
      contribute to the long-term health of Canadians.

PMID- 20057211
TI  - Notes from the Editor-in-Chief.

PMID- 20057209
TI  - Leveraging our collective investment in Canada's Healthcare System.
AB  - The pursuit of tangible mechanisms and measures to quantify the value-for-money
      proposition within Canada's healthcare system has become healthcare's own Holy
      Grail. A critical assessment and analysis of this age-old conundrum, as explored
      in the lead paper of this issue, forms the basis of this commentary which goes on
      to challenge readers to consider how healthcare providers can collectively act on
      the information and research available and begin to leverage investments already
      made with the goal of affecting real change across the system.

PMID- 20057212
TI  - Aging at home: integrating community-based care for older persons.
AB  - Integrating community-based health and social care has grabbed international
      attention as a way of addressing the needs of aging populations while
      contributing to health systems' sustainability. However, integrating initiatives
      in different jurisdictions work (or do not work) within very various
      institutional and structural dynamics. The question is, what transferable lessons
      can we learn to guide policy makers and policy innovators at the local level? In
      this paper, we consider "aging at home" as a policy option in Ontario, and
      beyond. In the first section, we focus on the problem, in effect, what not to do.
      Here, we briefly review findings from national and international research
      literature and from our own research in Ontario that identify the costs and
      consequences of non-systems of care for older persons. In the second part, we
      turn to solutions, in effect, what to do. Drawing on our recent scoping review of
      the international literature, we identify three guiding principles, as well as a
      number of recommendations, for integrating care for older persons, knowing that
      important details of how to put such initiatives "on the ground" will be provided
      by other contributors to this journal edition.

PMID- 20057213
TI  - Community exercise: a vital component to healthy aging.
AB  - Exercise plays a critical role in promoting healthy aging and in the management
      of chronic illness. In this paper, we provide an overview of the leading research
      regarding exercise and chronic illness, and the variables influencing exercise
      participation among persons with a chronic illness. We then examine the Empoli
      Adaptive Physical Activity (APA) program as a model program that has overcome
      many of the obstacles to exercise adherence. Piloted by Local Health Authority 11
      in Tuscany, Italy, APA has over 2,000 participants, and it provides tailored
      exercise opportunities for persons with stroke, back pain, Parkinson's disease or
      multiple sclerosis, among others illnesses. The Empoli APA program serves as a
      model community exercise program and is now being replicated throughout Tuscany
      and in the United States.

PMID- 20057214
TI  - Integrated care for vulnerable older people in Denmark.
AB  - This paper focuses on community-based services for vulnerable older people in
      Denmark. The main characteristics of the Danish case of integrated care are
      introduced, and the principles in the provision of community-based services and
      the overall organization and responsibility of these services are analyzed.
      Furthermore, the principles and the incentives behind the development of
      integrated care for older people in Denmark are discussed. On the basis of the
      Danish experience, the paper ends with a discussion of important characteristics
      of community care for vulnerable and disabled older people and significant
      factors in the process of developing integrated community care.

PMID- 20057215
TI  - Dementia care: linear links and networks.
AB  - The consequences of dementia, for both patients and primary caregivers, are
      formidable. Primary caregivers are often overburdened or are significantly at
      risk for becoming overburdened. How do we meet this substantial and complex
      social challenge, which is as yet insufficiently recognized? We must start
      looking for new forms of care and support, for more goal-oriented care while
      maintaining humane values. The problem of dementia demands that we follow more
      leads: new treatments and interventional care, greater use of technology, new
      divisions of labour among professionals and more empowerment of primary care. At
      issue is the organization of physical and social environments for patients with
      dementia that closely meet their needs. The road toward this goal is long and
      complicated, but a start has been made in the Netherlands.

PMID- 20057216
TI  - On Lok: a successful approach to aging at home.
AB  - The Program of All-inclusive Care for the Elderly (PACE) is a proven model for
      successfully delivering medical and long-term care services to seniors whose
      desire is to age at home. PACE is a vertically integrated system of care that is
      centred around the belief that it is better for the well-being of seniors with
      chronic care needs and their families to be served in the community whenever
      possible. Through this paper, we share On Lok's story and how the PACE model has
      become a national model, replicated in communities throughout the United States.

PMID- 20057217
TI  - From Denmark to Deep River: integrating care in small and rural communities in
      Ontario.
AB  - Integrating community-based health and social care for older persons is said to
      help individuals maintain high levels of independence, well-being and quality of
      life and contribute to health systems sustainability by moderating the demand for
      costly emergency services and inappropriate hospital care. Rural settings,
      however, pose challenges distinct from those in urban areas. Using North Renfrew
      Long-Term Care Services as a case study, this paper discusses the principles and
      practices of a small, rural community service agency located in Renfrew County,
      Ontario, that provides to its scattered populations a range of services across
      the care continuum. Services include community support programs, supportive
      housing and long-term care beds as well as an innovative 24-Hour Flexible In-Home
      Support Pilot program adapted from the ground breaking "night patrol" system in
      Denmark.

PMID- 20057218
TI  - Home care: from adequate funding to integration of services.
AB  - With the aging of the population, the healthcare system needs to shift from the
      actual hospital-centred system developed in the past century for dealing with
      acute diseases and a young population toward a home-centred system, more
      appropriate for serving older people with chronic diseases. Funding of home care
      should not only be significantly increased but also be managed differently. We
      propose the introduction of an autonomy support benefit (ASB) to cover costs
      related to disabilities, irrespective of living environment, and to set up a
      public universal autonomy insurance program that will cover the ASB. This
      insurance should be at least partly capitalized to provide for the aging of the
      population and to ensure intergenerational equity. Also, since the home is a much
      more complicated service-delivery environment than the hospital, these services
      must be coordinated and integrated. The Program of Research to Integrate the
      Services for the Maintenance of Autonomy (PRISMA) is a coordination-type model of
      integration that was implemented and evaluated in three areas (one urban and two
      rural) in and around Sherbrooke, Quebec. A four-year longitudinal quasi
      experimental study with over 1,500 participants demonstrated its efficiency in
      improving system effectiveness at no extra cost.

PMID- 20057219
TI  - Accountability, responsiveness and quality for clients model of home support: a
      model for improved home support services to promote aging at home.
AB  - As the proportion of older adults increases within the Canadian population,
      healthcare systems across the country are facing increased demands for home-based
      services, including home care nursing, rehabilitation, case management, adult day
      programs, respite, meal programs and home support. Home support is one of the
      core care services required in the community to enable older adults to remain at
      home as long as possible. In 2006, Vancouver Community introduced a new home
      support delivery and performance management model: the Accountability,
      Responsiveness and Quality for Clients Model of Home Support (ARQ Model) (VCH
      2006). The main components of the ARQ Model are an expanded use of "cluster care"
      along with stable monthly funding for high-density buildings and neighbourhoods;
      the introduction of specific monthly and quarterly quality performance reporting;
      and the implementation of performance-based funding for home support. This
      article discusses the setup of the ARQ model, its ongoing evaluation and results
      achieved thus far.

PMID- 20057222
TI  - Methods being used and researched to enhance healthcare. Editorial.

PMID- 20057220
TI  - Canada's Veterans independence program: a pioneer of "aging at home".
AB  - The Veterans Independence Program (VIP) was developed in the late 1970s to
      promote the independence and aging at home of Second World War veterans. This
      paper describes VIP's origins, core services and its service-delivery approach.
      It also summarizes program expenditures and client trends, presents the results
      of research studies of program impact and effectiveness and discusses lessons
      learned and best practices.

PMID- 20057223
TI  - The myth of the "natural CEO".

PMID- 20057224
TI  - CHSRF accelerating change: Health infostructure and the cultural imperative.

PMID- 20057225
TI  - CIHI survey: Hospital costs for preterm and small-for-gestational age babies in
      Canada.
AB  - In 2006-2007, more than 54,000 (or one in seven) babies across Canada were born
      preterm or small for their gestational age (SGA). These babies are often at
      higher risk for morbidity and mortality than are full-term babies with normal
      birth weight, and account for a disproportionately high percentage of healthcare
      costs among newborns. This article highlights key findings from a recent report
      by the Canadian Institute for Health Information, Too Early, Too Small: A Profile
      of Small Babies across Canada, and provides information on the hospital costs
      among low birth weight, preterm and SGA babies. Birth weight and gestational age
      were found to be important determinants of hospital costs - as birth weight and
      gestational age decreased, average in-hospital costs increased. Furthermore,
      multiple-birth babies had higher hospital costs than did singleton babies. As in
      other areas of the health system, information relating to costs and spending can
      inform neonatal and obstetrical health planning and decision-making.

PMID- 20057226
TI  - ICES report: Appropriateness: the next frontier in the quest for better access to
      CT and MRI.

PMID- 20057227
TI  - Profile: Ed Brown and the development of the Ontario Telemedicine Network.

PMID- 20057228
TI  - Increasing value for money in the Canadian healthcare system: new findings on the
      contribution of primary care services.
AB  - This article presents a major new finding in regard to the value for money of
      primary care services. It was found that the more higher-care-needs patients were
      attached to a primary care practice, the lower the costs were for the overall
      healthcare system (for the total of medical services, hospital services and
      drugs). The majority of the cost reductions stemmed from decreases in the costs
      of hospital services. Thus, for higher-care-needs patients, it appears that the
      nature of the physician-patient relationship is related to reductions in hospital
      costs. For example, for very-high-care-needs diabetic patients, the average
      annual hospital cost in fiscal 2007-2008 for those in the lowest attachment group
      was $16,988, whereas the hospital costs for those in the highest attachment group
      was $5,909. The results obtained were even more striking for patients with
      congestive heart failure. A series of multiple regression analyses were
      conducted, and the results were very consistent: attachment to practice was the
      best predictor in regard to cost and was a more significant predictor than other
      variables that were related to healthcare costs, such as age. These findings
      support the general literature on the benefits of primary care and the continuity
      of care.

PMID- 20057229
TI  - Evaluating nursing staff mix in long-term care: a comprehensive framework for
      decision-makers.
AB  - The connection between care-provider type and patient outcomes is well
      established. Less well understood, however, is how to evaluate staff mix decision
      making aimed at maximizing quality outcomes for care recipients, nursing staff
      and healthcare systems. From May through November 2008, Eastern Health, the
      largest regional integrated health authority in Newfoundland and Labrador,
      conducted a Staff Mix Intervention Project designed, in part, to gauge the
      effectiveness of the Evaluation Framework to Determine the Impact of Nursing
      Staff Mix Decisions in assessing the impact of nursing staff mix changes in long
      term care. Results reveal that the Evaluation Framework is a useful tool for
      managers and other decision-makers to use when measuring the comprehensive
      effects of staff mix changes and planning further human resources modifications.

PMID- 20057230
TI  - Development of a critical care triage protocol for pandemic influenza:
      integrating ethics, evidence and effectiveness.

PMID- 20057231
TI  - Do clinical practice guidelines influence length of stay in ontario acute care
      hospitals?
AB  - Following a systematic review of literature describing the relationship between
      the use of clinical practice guidelines (CPGs) and length of stay (LOS), we
      conducted a secondary analysis of the same relationship using data from Ontario
      acute care hospitals over two years. Unlike the original systematic review, this
      analysis did not find a strong relationship between CPG usage and LOS: the
      relationship between CPG usage and LOS was statistically significant only in the
      disease states of pneumonia and prostatectomy. Possible reasons for this outcome
      are explored, as are limitations, policy implications and suggestions for future
      research.

PMID- 20057232
TI  - Overcoming barriers when implementing evidence at the bedside.
AB  - Implementing evidence is the basis for improving the organization of care, with
      the ultimate goal of achieving optimal patient outcomes. As implementing evidence
      can be a challenging task due to human and system barriers, we propose an
      innovative framework to facilitate knowledge translation at the bedside. This
      model is based on a problem-solving approach that was tested in the field of
      critical care. This method can be adapted to any healthcare environment as the
      problems encountered when trying to implement guidelines and protocols are
      common.

PMID- 20057233
TI  - Community networks in chronic disease management.
AB  - Community networks are being established as part of the Chronic Disease
      Management program in Edmonton, Alberta. These networks are programs and services
      from profit and not-for-profit organizations that support people with chronic
      conditions to address lifestyle choices and issues. Evidence-informed standards
      and criteria have been developed that have to be met to belong to such a network.
      The community network approach is developing a "community" of resources that are
      available and committed to assist healthcare professionals and the public with
      health promotion for people with chronic conditions.

PMID- 20057234
TI  - Variability in the surgical management of carpal tunnel syndrome: implications
      for the effective use of healthcare resources.
AB  - Medicine has been said to be as much art as science, where physicians invoke
      their individual skills and judgment to address the unique aspects of each
      presenting patient. Yet to what extent should physicians exercise their own
      discretion in determining the use rates of hospital resources? This article
      examines the results of a study on surgeon use of surgical setting and anesthetic
      technique for carpal tunnel release (CTR) surgery - a simple, low-risk surgical
      procedure that can be performed in either a formal operating room or a minor
      surgical setting, using local, regional or general anesthetic. The selected
      combination of surgical setting and anesthetic technique employed by a surgeon
      has not been standardized and can significantly impact both patient outcomes and
      administrative healthcare costs for hospital resources, equipment and
      pharmaceuticals. While a certain amount of variability in surgical management is
      necessary to allow clinicians to practise their "art," policy makers have an
      opportunity to standardize some surgeon practices to control costs, particularly
      when those practices are found to be as strongly influenced by the subjective
      attitudes of individual surgeons as by evidence-based science and economics.

PMID- 20057235
TI  - Patient relations "road show" at university health network.
AB  - COMPLAINTS, COMPLAINTS, COMPLAINTS! Where are my results? Why do I have to wait
      so long? Is anybody listening? Does anybody care? I'm a taxpayer; I am entitled!
      Sound familiar? These are the kinds of things we hear on a daily basis from
      patients and family members.

PMID- 20057236
TI  - Innovative technology conserves resources and generates savings: a case study
      from the Sunnybrook Regional Processing Centre.
AB  - The regional processing centre at Sunnybrook Health Sciences Centre recently
      faced the substantial challenge of increasing cleaning capacity to meet the
      current workload and anticipated future demand without increasing its operating
      budget. The solution, upgrading its cleaning and decontamination system to a
      highly automated system, met both objectives. An analysis of the impact of the
      change found that the new system provided additional benefits, including improved
      productivity and cleaning quality; decreased costs; reduced water, electricity
      and chemical use; improved worker safety and morale; and decreased overtime.
      Investing in innovative technology improved key departmental outcomes while
      meeting institutional environmental and cost savings objectives.

PMID- 20057237
TI  - More doctors or better care?
AB  - The Canadian Medical Association's More Doctors, More Care campaign seeks to
      align physician supply targets with policy decisions elsewhere in the
      Organisation for Economic Co-operation and Development (OECD). Using OECD data
      for 19 countries to assess the relationship between physician supply and
      healthcare outcomes, we have determined that there is no association between
      avoidable mortality and overall physician supply. Similarly, there is no
      relationship between avoidable mortality and general practitioners and family
      physicians per capita, specialists per capita, nurses per capita, doctors and
      nurses per capita or health expenditures per capita. These findings should move
      us to recognize that (a) more doctors will not necessarily translate into better
      healthcare outcomes for Canadians and (b) it is in Canadians' better interests
      that we instead focus on realizing opportunities to improve access to high
      quality care and to ensure that changes in physician turnover do not threaten the
      current generalist-to-specialist mix.

PMID- 20057238
TI  - Participatory storytelling online: a complementary model of patient satisfaction.
AB  - Measuring patient satisfaction is an important quality improvement technique. The
      World Wide Web offers new approaches to understanding patient satisfaction and
      stories about healthcare encounters. In this paper, we suggest that there is a
      wealth of patients' stories being told online, in real time, on social networking
      and on social rating websites. This patient-generated, publicly available
      information can complement existing patient satisfaction data and can provide
      insights into patients' values, perspectives and expectations - and can suggest
      ways to improve the patient's experience along the continuum of care.

PMID- 20057239
TI  - A case study examining the impacts of conferencing technologies in distributed
      healthcare groups.
AB  - As healthcare groups continue to communicate and collaborate at a distance,
      information and communication technology (ICT) has come to play an increasingly
      important role in supporting such interactions. In this paper, we describe key
      lessons learned from a two-year case study (2004-2006) on the impacts of
      conferencing technologies on social interaction norms within knowledge exchange
      groups.

PMID- 20057240
TI  - E-health leads Nova Scotia's healthcare transformation.
AB  - Nova Scotia's healthcare policy direction seems well-defined and well-established
      for the foreseeable future. This is the case, despite the recent electoral
      transition from a Progressive Conservative to a New Democratic Party government
      for the first time in the province's history; and despite the threat of the
      province's net direct debt increasing through 2012, after eight years of
      declining net direct debt as a percentage of the province's gross domestic
      product. As well, little public consideration is being given to disrupting the
      current regional healthcare organizational structure by further consolidating the
      province's nine district health authorities (DHA), as occurred last year in
      Alberta and New Brunswick. Moreover, the Health Information Technology Services
      Program of Nova Scotia (HITS-NS), the province's shared IT services or provincial
      service delivery organization, is steadily expanding the inventory of clinical,
      financial, and administrative software applications hosted for eight DHAs on a
      common Meditech Client-Server platform, as well as some applications for Capital
      Health DHA 9 (CDHA) and IWK Health Centre (IWK), the province's consolidated
      women's and children's hospital located in Halifax.

PMID- 20057242
TI  - Healthcare systems integration in Canada.

PMID- 20057243
TI  - All together now: a conceptual exploration of integrated care.
AB  - Integrated care is a key strategy in reforming health systems around the world.
      Despite its importance, the concept's polymorphous nature and lack of specificity
      and clarity significantly hamper systematic understanding, successful application
      and meaningful evaluation. This article explores the many definitions, concepts,
      logics and methods found in health system and service integration. In addition to
      framing this evolving, albeit imprecise field, the article summarizes the main
      elements or building blocks of integrated care and suggests a way to address its
      various complexities and unknowns in a real-world sense.

PMID- 20057244
TI  - Ten key principles for successful health systems integration.
AB  - Integrated health systems are considered part of the solution to the challenge of
      sustaining Canada's healthcare system. This systematic literature review was
      undertaken to guide decision-makers and others to plan for and implement
      integrated health systems. This review identified 10 universal principles of
      successfully integrated healthcare systems that may be used by decision-makers to
      assist with integration efforts. These principles define key areas for
      restructuring and allow organizational flexibility and adaptation to local
      context. The literature does not contain a one-size-fits-all model or process for
      successful integration, nor is there a firm empirical foundation for specific
      integration strategies and processes.

PMID- 20057245
TI  - Integrated care needs integrated information management and technology.
AB  - Integrated care entails that professionals from different organizations have to
      work together in a team-oriented way to provide high-quality care for a patient.
      This requires that healthcare professionals share information about--and with-
      patients at appropriate points in the care or treatment process. The necessary
      infrastructural arrangements--such as shared patient records, regional
      collaboration and a clear, transparent incentive structure--must be in place. It
      is increasingly hard to imagine integrative initiatives without a strong
      information management and technology component. However, information is a
      necessary condition but not sufficient to achieve integrated care; organizational
      change is the more critical component.

PMID- 20057246
TI  - Integrated health systems and integrated knowledge: creating space for putting
      knowledge into action.
AB  - The capacity to innovate and share knowledge is not well developed within health
      systems. In this paper we highlight essential structures, principles and
      processes for successful implementation of knowledge utilization strategies in
      complex health systems. We demonstrate essential links between systems that
      support knowledge utilization and governance, change management, information
      management and process improvement.

PMID- 20057247
TI  - Process improvement and supply and demand: the elements that underlie
      integration.
AB  - Integration relies on a series of key change strategies connected by a
      fundamental dynamic: system capacity has to match demand or it will ultimately
      result in expanding delay and system failure. A balance of supply and demand is
      necessary for successful system performance. If demand and capacity are balanced,
      then delays are not required.

PMID- 20057248
TI  - Making integration work requires more than goodwill.
AB  - Over the past three years I have had the opportunity to be involved in two
      integration projects regarding cancer services. Both projects crossed
      jurisdictional, geographical and healthcare-provider boundaries and used
      cooperation and collaboration to work toward the goal of an integrated, quality,
      multi-disciplinary, seamless, patient-centred approach to cancer care. The
      projects have provided a perspective of what worked well and what could be
      improved when integrating healthcare services across organizational and provider
      boundaries. Governance emerged as a key determinant of project progress and
      successful change.

PMID- 20057249
TI  - Engaging the head and heart: leading change.

PMID- 20057250
TI  - Introduction to case studies on integration.

PMID- 20057251
TI  - Health Link Alberta: a model for successful health service integration.
AB  - Health Link Alberta is a model of successful regional integration. Launched as a
      single-region service in 2000, Health Link Alberta was rolled out as a province
      wide service in 2003, operating as one service from two sites (Calgary and
      Edmonton). Provincial integration of Health Link Alberta was successful because
      it took the time to establish collaborative governance structures, build
      relationships with regional and provincial stakeholders, recognize and
      accommodate regional and local needs, and develop the processes and tools that it
      needed to deliver a quality, consistent and accessible service for all Albertans.
      Within three years, Health Link Alberta achieved 63% awareness and 46%
      utilization among all Alberta households.

PMID- 20057252
TI  - Improving patient access to medical services: preventing the patient from being
      lost in translation.
AB  - The Medical Access to Service project was initiated to broadly engage
      participants in the health system to collectively improve service integration and
      patient access to primary care and specialist medical services. The Conference
      Model (the Axelrod Group, Willmette, IL) was used as a change vehicle. The ideal
      design was translated into the creation of central access and triage (CAT)
      processes across medical specialties, development of prioritization tools and
      implementation of access and efficiency through Alberta AIM (access improvement
      measures) collaboratives for process re-engineering. The ultimate goal for all
      Albertans who need care is one point-of-access--one standardized process to
      ensure equal access for all regardless of where they live.

PMID- 20057253
TI  - Enhancing patient care via a pharmacist-managed rural anticoagulation clinic.
AB  - Integrating specialized pharmacist services and follow-up with the laboratory,
      home care nursing, retail pharmacy and physicians can ensure optimal outcomes for
      patients receiving anticoagulation, or "blood thinner," therapy. Improved patient
      education and discharge care planning can bridge disconnects, enable patients to
      better manage their care and ensure better patient outcomes and more effective
      use of health system resources. Specially trained pharmacists can provide safe
      and effective management of a high-alert medication to help prevent potentially
      life-threatening clots or bleeding. With advanced prescribing authorization, the
      pharmacist can seamlessly provide this service both locally in a community and
      via Telehealth to surrounding areas, potentially for any Albertan. Warfarin
      therapy may be lifelong or short-term (three to six months), but all patients
      require regular monitoring with blood tests. Many variables, both lifestyle and
      medication related, can impact therapy, and through extensive education and
      access via telephone to an "expert" for questions and follow-up of blood tests,
      patients are empowered to better regulate their anticoagulants. Anticoagulation
      pharmacists, as part of an AMS (anticoagulation management service), can provide
      a continuum of care for patients while in hospital, when discharged home, as an
      outpatient in the community or as a resident of a long-term care facility or
      seniors' home.

PMID- 20057254
TI  - Organizing care across the continuum: primary care, specialty services, acute and
      long-term care.
AB  - Primary care networks (PCNs) facilitate integration of healthcare across the
      continuum. The Calgary Rural PCN implemented a community-based model where
      physicians and Alberta Health Services work together to deliver primary care
      addressing local population needs. This model is highly valued by physicians,
      decision-makers and providers, with early impacts on outcomes.

PMID- 20057255
TI  - Integrated stroke care across a province--is it possible?
AB  - Using a patient's perspective on her journey through the care continuum, this
      article describes Alberta's newly integrated provincial stroke system. It then
      explains the integrative system development that has occurred both within the
      Edmonton area and the province to allow this patient's successful post-stroke
      experience.

PMID- 20057256
TI  - The Alberta Cardiac Access Collaborative: improving the cardiac patient journey.
AB  - The Alberta Cardiac Access Collaborative (ACAC) is a joint initiative of
      Alberta's health system to improve access to adult cardiac services across the
      patient journey. ACAC has created new care delivery models and implemented best
      practices across Alberta in four streams across the continuum: heart attack,
      patient navigation, heart failure and arrhythmia. Emergency medical providers,
      nurses, primary care physicians, hospitals, cardiac specialists and clinicians
      are all working together to integrate services, bridge jurisdictions and
      geography with one aim--improving the patient journey for adults in need of
      cardiac care.

PMID- 20057257
TI  - Implementation and evaluation of a community-based medication reconciliation
      (CMR) system at the hospital-community interface of care.
AB  - The WestView community-based medication reconciliation (CMR) aims to decrease
      medication error risk. A clinical pharmacist visits patients' homes within 72
      hours of hospital discharge and compares medications in discharge orders, family
      physicians' charts, community pharmacy profiles and in the home. Discrepancies
      are discussed and reconciled with the dispenser, hospital prescriber and follow
      up care provider. The CMR demonstrates successful integration that is patient
      centred and standardized, bridging the hospital-community interface and improving
      information flow and communication channels across a family-physician-led multi
      disciplinary team. A concurrent research study will evaluate the impact of CMR on
      health services utilization and to develop a risk prediction model.

PMID- 20057258
TI  - Alberta's systems approach to chronic disease management and prevention utilizing
      the expanded chronic care model.
AB  - Alberta's integrated approach to chronic disease management programming embraces
      client-centred care, supports self-management and facilitates care across the
      continuum. This paper presents strategies implemented through collaboration with
      primary care to improve care of individuals with chronic conditions, evaluation
      evidence supporting success and lessons learned from the Alberta perspective.

PMID- 20057259
TI  - From the editor-in-chief: scared to need nursing care.

PMID- 20057261
TI  - Alert--return of 1990s healthcare reform.
AB  - Remember the 1990s? In case you don't, there was a major recession and hospitals
      found themselves squeezed for funds. A movement called "healthcare reform" was
      instituted across Canada to reduce costs and balance budgets. Nurses bore the
      brunt of the so-called reforms, which resulted in * merging of hospitals and loss
      of nursing positions; * elimination of nurse managers' positions and expansion of
      the span of control of those who remained, so that they found themselves managing
      two to four units and responsible for 100 to 200 nurses; * elimination of RN
      positions and substitution of licensed practical nurses or non-regulated workers;
      * replacing full-time RN positions with part-time positions without fringe
      benefits; * absence of nursing positions for new graduates and nurses who had
      been displaced, driving them to seek employment in the United States (the
      majority did not return to Canada); * collapse of the applicant pool to schools
      of nursing, which took a decade to rebound to pre-reform days (the drop in
      graduates over several years during this period is in part responsible for the
      shortage of nurses today); * dramatic loss of job satisfaction by nurses, which
      has still not recovered; and * a prevalent sense that nurses were disposable and
      mattered little in the broad healthcare system.

PMID- 20057262
TI  - Exploring the expectations of current and potential ACEN members.

PMID- 20057263
TI  - Informatics around the globe.

PMID- 20057264
TI  - A return to diploma-prepared registered nurses.
AB  - A quarter of a century ago, the nursing profession in Canada took a bold step: to
      establish baccalaureate preparation in nursing as the standard for practice as a
      registered nurse in Canada. Towards that end, hospital schools of nursing gave
      way to collaborative programs designed to help hospital and college diploma
      nursing students make the transition into baccalaureate nursing programs. It is
      thus paradoxical that, today, the nursing profession in Canada should do anything
      to jeopardize its goal to have RNs prepared at the baccalaureate level. The
      purpose of this paper is to focus Canadian nurse leaders' attention on that very
      possibility, given that some professional nursing organizations in Canada have
      conceptualized a future RN practice that could result in the emergence of a new
      kind of healthcare professional and a return to diploma preparation of RNs.

PMID- 20057265
TI  - Improving gerontology content in baccalaureate nursing education through
      knowledge transfer to nurse educators.
AB  - Across practice settings, most nursing care is provided to older adults. Yet most
      nurses receive limited education to care for older adults, especially those with
      complex needs. A Knowledge Exchange Institute for Geriatric Nursing Education
      brought together 31 Canadian nursing faculty members and nursing doctoral
      students and provided them with tools and resources to enhance teaching and
      curriculum in baccalaureate nursing programs. Guided by the Knowledge-to-Action
      Process model, participants received usable summaries of the best research
      evidence about care for older adults and tools to increase the likelihood of
      successful integration of these resources in their teaching and curriculum.
      Feedback from participants indicates that their personal goals and the goals of
      the Knowledge Exchange were met. Through a public interactive wiki, participants
      and others will continue the process of knowledge exchange to improve nursing
      education and nursing care for older persons.

PMID- 20057266
TI  - Effects of leadership and span of control on nurses' job satisfaction and patient
      satisfaction.
AB  - BACKGROUND: Hospital restructuring has resulted in nurse managers' having direct
      responsibility for a greatly expanded number of units and staff. However, very
      little research has examined the impact of these larger spans of control on nurse
      and patient outcomes. OBJECTIVE: This study examined the relationships between
      leadership style, span of control, nurses' job satisfaction and patient
      satisfaction, as well as the moderating effect of span of control on the
      relationship between leadership style and the two outcomes. METHODS: The study
      was conducted at seven teaching and community hospitals with a sample of 51
      units, 41 nurse managers, 717 nurses and 680 patients. Data analyses included
      multiple regression and hierarchical linear modelling. RESULTS: The study
      findings provided support for the theoretical relationships among leadership
      style, span of control, nurse job satisfaction and patient satisfaction. In
      addition, the results showed that higher spans of control decreased the positive
      effects of transformational and transactional leadership styles on job
      satisfaction and patient satisfaction, and increased the negative effects of
      management by exception and laissez-faire leadership styles on job satisfaction.
      DISCUSSION: Leadership matters, and certain leadership styles, particularly
      transformational, are better than others. Span of control also matters: the wider
      the span, the lower the nurses' job satisfaction and patient satisfaction.
      However, as spans of control increase in size, no leadership style, even
      transformational, can overcome the negative effects.

PMID- 20057267
TI  - Leadership for ethical policy and practice (LEPP): participatory action project.
AB  - Within Canada's fast-paced, ever-changing healthcare environment, providers are
      experiencing difficulty practising according to their professional ethical
      standards, leading many to experience moral or ethical distress. Limited
      attention has been paid to improvements in the ethical climate in healthcare
      settings in research focusing on nurses' workplaces. In this three-year study, we
      focused on how the ethical climate in healthcare delivery can be improved and how
      the use of participatory action research methods can lead to continued
      enhancements and lasting changes in services delivery. Together, we developed
      strategies for taking action, aimed at improving the quality of the work
      environment. This action involved both nurses in direct care and those in key
      leadership positions (CNOs or their equivalents). Through the active
      participation of those for whom the research-based change was intended, these
      strategies were tested in various sites across British Columbia and can be used
      as templates or designs for use in other settings. A key component of the success
      of the projects and action plans that were created was the integral involvement
      of nurse leaders through all phases.

PMID- 20057268
TI  - From the editor-in-chief.

PMID- 20057269
TI  - Deliveries among adolescent mothers in rural Bangladesh: who provides assistance?
AB  - OBJECTIVES: This paper sought to identify factors associated with modes of
      delivery assistance among adolescent mothers in rural Bangladesh. METHODOLOGY:
      Bangladesh Demographic and Health Survey of 2004 data for the last 5 years (N =
      867) were used. Univariate statistical analysis and multivariate logistic
      regression methods were employed in analyzing the data. RESULTS: We observed that
      almost all adolescent deliveries (93.6 %) took place at home, and most (80.1%)
      were assisted by untrained traditional birth attendants, relatives or neighbours.
      Only 8.8% were attended by medically trained persons. Main factors affecting
      delivery practices among adolescents were mass media exposure, parents'
      education, antenatal care received, type of toilet facilities and visits by
      family planning workers (FPW), wanted last child and told about pregnancy
      complications. CONCLUSIONS: RESULTS indicate several policy options to improve
      outcomes for adolescent mothers: (a) create awareness of appropriate behaviours
      during pregnancy, delivery and post-partum period, (b) ensure maternal healthcare
      centres are available, especially rurally, for antenatal care, expand and improve
      the quality of home births by trained providers and introduce post-partum visits,
      (c) increase the number of visits by family welfare visitors/family welfare
      assistants (FWV/FWA), and (d) emphasize adolescent education to make a lasting
      impact on the overall health of adolescent mothers.

PMID- 20057270
TI  - Factors influencing mothers' role in convulsion treatment among under-five
      children in Ibadan, Nigeria.
AB  - Convulsion among children between six months and five years is a major
      contributor to childhood mortality in less-developed societies, especially in sub
      Saharan Africa. Most studies on under-five deaths have ignored the influence of
      socio-demographic and environmental factors as they relate to causes of the
      thematic health condition and available therapies. This study investigated
      mothers' perception of convulsion causation, relevant signs and symptoms, and the
      influence of socio-economic status on mothers' choice of remedies. The research
      was conducted in Ibadan, southwest Nigeria, which is densely populated with
      mainly Yoruba-speaking people. The study population comprised mothers who, at the
      time of fieldwork for the present analysis, had at least one under-five child.
      Five hundred questionnaire respondents were selected through a multistage
      sampling technique, and 14 in-depth interviews (IDIs) were conducted among
      different categories of women identified through the snowball technique.
      Voluntary Social Action Theory and the Health Belief Model were used in
      explaining the relationship between the dependent and independent variables. The
      findings show that the remedies mothers chose were strongly influenced by socio
      demographic factors such as marriage type, religion, level of education,
      occupation and place of residence. It is strongly suggested that interventions,
      health policies and programs should focus on how best to empower women to
      effectively utilize medical information that will enable them recognize symptoms
      of this common health condition and/or undertake preliminary therapies that
      contribute positively to convulsion prevention or treatment.

PMID- 20057271
TI  - Social stigma and quality of life among rural-to-urban migrants in China: a
      comparison with their rural counterparts.
AB  - Social stigma has been identified as a major concern in healthcare. Its
      association with quality of life among migrants is rarely assessed. Using data
      collected through a cross-sectional survey among 1,006 rural-to-urban migrants
      and 1,020 rural residents in China, this study examines the experience of
      stigmatization in relation to four domains of quality of life. Rural-to-urban
      migrants perceived a higher level of social stigma and a lower level of quality
      of life than their rural counterparts. Multiple regressions indicated the
      importance of social stigma in accounting for subjective quality of life for
      migrants. In addition, personal income, family economic status and health status
      were positively associated with increased quality of life. Social stigma has a
      significant influence on quality of life among rural-to-urban migrants in China.
      Future interventions should seek to improve public attitudes to rural-to-urban
      migrants and generate action to eliminate stigma, discrimination and prejudice.

PMID- 20057272
TI  - Moving beyond racial categorization in understanding health disparities.

PMID- 20057273
TI  - Human nomenclature: from race to racism.
AB  - Throughout time, evolutionary biologists have attempted to classify human beings
      according to a nomenclature based on supposed patterns of biological differences
      that have been used to suggest hierarchical categories. Recent genetic evidence
      disproves the assumption that races are genetically distinct human populations.
      Several studies refute human categorization as a severely flawed yardstick. For
      many, race is a construct that must be overcome in order to eradicate racism.
      Personal experiences of racism, harassment and discrimination are associated with
      multiple indicators of poorer physical and mental health status. Additionally,
      socio-economic differentials are likely to be a fundamental explanation for the
      observed inequalities in health status among minority groups. This commentary
      examines the discrepancies that race, ethnicity and similar human nomenclatures
      present. Furthermore, the potentially harmful consequences of the "scientific"
      use of race, in the form of stereotyping and racism, are discussed.

PMID- 20057274
TI  - Seven Chinese patients with buckwheat allergy.
AB  - Buckwheat is an important crop in China and is also known as an important potent
      allergen in the population. Here, we report a series of 7 Chinese patients with
      buckwheat allergy, which has never been reported previously in China. Mean age
      was 20 years at diagnosis. Patients' symptoms were respiratory, gastrointestinal,
      cutaneous, and anaphylactic. The routes of exposure were varied. Laboratory
      allergy test showed that buckwheat-specific IgE levels in all patients were
      remarkably elevated. Allergen avoidance was the best treatment in these cases.
      The data suggest that buckwheat can induce various clinical manifestations.
      Anaphylaxis might be characterized by severe symptoms. Buckwheat pillow is an
      important source of exposure to buckwheat in China and other Asian countries.
      Therefore, public education with effective avoidance measures should be an
      integral part of the management strategy.

PMID- 20057275
TI  - Hypoalbuminemia and lymphocytopenia in patients with decompensated biventricular
      failure.
AB  - BACKGROUND: In patients hospitalized with decompensated biventricular failure
      having hypoalbuminemia and lymphocytopenia without underlying hepatic or renal
      disease, we addressed the presence of a protein-losing enteropathy (PLE).
      METHODS: We studied 78 patients having a dilated cardiomyopathy, who were
      hospitalized with congestive heart failure (CHF) and hypoalbuminemia of uncertain
      origin. In the first 19 patients, we investigated the presence of PLE using Tc
      Dex scintigraphy together with serum albumin 2 to 4 weeks later when compensation
      had been restored. In the next 59 patients, presenting with reduced serum albumin
      and relative lymphocyte count at admission, these parameters were again monitored
      (2-4 weeks) later when symptoms and signs of CHF had resolved. RESULTS: PLE,
      documented by Tc-Dex(70) scintigraphy, was found in 10 of 19 patients and whose
      hypoalbuminemia (2.7 +/- 0.1 g/dL, mean +/- standard error of mean) were
      corrected (3.3 +/- 0.1 g/dL; P < 0.05) with the resolution of CHF, whereas in the
      9 patients without a PLE, reduced baseline serum albumin (2.6 +/- 0.1 g/dL)
      failed to improve on follow-up (2.6 +/- 0.2 g/dL) in keeping with malnutrition.
      Relative lymphocyte count was reduced (14.6 +/- 1.5%) in patients with PLE but
      was normal (21.4 +/- 3.3%; P < 0.05) in those without PLE. Serum albumin and
      relative lymphocyte count were each reduced at admission (2.8 +/- 0.1 g/dL and
      14.4 +/- 1.0%, respectively) in 59 patients and increased (P < 0.05) to normal
      values (3.5 +/- 0.1 g/dL and 24.9 +/- 1.0%) 2 to 4 weeks after they were
      compensated. CONCLUSIONS: Enteral losses of albumin and lymphocytes account for
      the reversible hypoalbuminemia and lymphocytopenia found in patients hospitalized
      with CHF having splanchnic congestion.

PMID- 20057276
TI  - Differential Th1/Th2 chemokine expression in interstitial pneumonia.
AB  - BACKGROUND: T-helper (Th)-2 background in the lungs may favor the development of
      pulmonary fibrosis. We hypothesized that usual interstitial pneumonia (UIP) and
      nonspecific interstitial pneumonia (NSIP), major pathologic patterns of chronic
      interstitial pneumonia, would have different expression profiles of TH1 and TH2
      chemokines. METHODS: Total RNA was isolated from lung tissues obtained by
      surgical biopsy (18 cases of UIP and 29 cases of NSIP). The expression of ligands
      for CXCR3 [TH1 cells chemoattractant: monokine induced by interferon (IFN)-gamma
      (MIG), IFN-gamma-inducible protein of 10 kD, and IFN-inducible T cell alpha
      chemoattractant] and ligands for CCR4 [TH2 cells chemoattractant: thymus- and
      activation-regulated chemokine and macrophage-derived chemokine (MDC)] were
      analyzed by real-time reverse transcriptase polymerase chain reaction. RESULTS:
      MIG and IFNgamma-inducible protein of 10 kD expression were significantly higher
      in NSIP compared with UIP. MDC expression was increased in UIP compared with
      NSIP, although the difference was not significant. MIG/MDC is significantly
      elevated in NSIP but not UIP. Interestingly, MIG/MDC was significantly higher in
      NSIP group 3 (NSIP with extensive fibrosis) compared with UIP. CONCLUSIONS: These
      results may indicate that these 2 diseases have a different pathophysiology.
      MIG/MDC may be a useful marker to distinguish these 2 diseases.

PMID- 20057277
TI  - A 42-year-old man with shortness of breath and abdominal pain.

PMID- 20057278
TI  - Clinical course and outcome of cocaine-induced pneumomediastinum.
AB  - BACKGROUND AND OBJECTIVES: Cocaine inhalation has been linked to the development
      of pneumomediastinum. The aim of this review was to identify the clinical course
      and outcome of spontaneous pneumomediastinum caused by cocaine use. MATERIAL AND
      METHODS: We performed a literature search in English language using PubMed. We
      included all case reports and case series of spontaneous pneumomediastinum caused
      by cocaine use. Twenty-three case reports and 7 case series describing 40
      patients were identified. In addition, 2 young adults who were admitted to our
      teaching hospital with cocaine-induced pneumomediastinum were included in this
      review. RESULTS: Among 42 patients, 93% were presented with chest pain and 64%
      had subcutaneous emphysema. Symptoms subsided after a median of 24 hours, and
      radiological abnormalities abated after 2 to 30 days, with a median of 4.5 days.
      Pneumothorax was present in 19% of patients, and only 1 required chest tube
      placement. Patients were discharged with full recovery after 1 to 6 days, with a
      median of 2 days. CONCLUSION: Cocaine-induced pneumomediastinum is a benign
      condition. A short observation period with outpatient follow-up is appropriate in
      the majority of patients. Invasive procedures have a low yield and should be
      based on a high degree of clinical suspicion for esophageal rupture or bronchial
      tree laceration.

PMID- 20057279
TI  - Erythema multiforme associated with gemfibrozil monotherapy.
AB  - BACKGROUND: A case of erythema multiforme associated with gemfibrozil
      monotherapy. METHODS AND RESULTS: A 46-year-old man with hyperlipidemia was
      treated with 600 mg gemfibrozil twice a day. On the fifth day of treatment, skin
      lesions consistent with erythema multiforme appeared. With the discontinuation of
      the treatment and start of a topical steroid treatment, the lesions recovered
      after 4 weeks. After 6 months, when gemfibrozil therapy was restarted, lesions
      reappeared on the fourth day of therapy. Lesions recovered again following the
      previous treatment strategies after 4 weeks. An objective casualty assessment
      suggests that erythema multiforme was probably related to gemfibrozil
      monotherapy. CONCLUSION: Patients starting gemfibrozil therapy should be warned
      about the occurrence of erythema multiforme in addition to previous reported and
      established side effects.

PMID- 20057280
TI  - Obturator hernia: a diagnostic challenge of small-bowel obstruction.
AB  - Obturator hernia is relatively rare and is a diagnostic challenge in the
      emergency department because the hernia mass is usually concealed beneath the
      pectineus muscle. We report the case of a 91-year-old emaciated woman with an
      incarcerated obturator hernia. The hernia was discovered early in the emergency
      department by computed tomography and was reduced by emergency laparotomy. The
      Howship-Romberg sign and pain from the ipsilateral thigh to the knee are
      important clinical manifestations raising suspicion of obturator hernia, but
      these did not occur in our patient. One of the clinical clues in our patient was
      small-bowel obstruction of unknown origin, diagnosed by computed tomography. We
      emphasize that emergency physicians should keep a high index of clinical
      suspicion for obturator hernia when encountering small-bowel obstruction in
      emaciated elderly women. Although we cannot shorten the time from onset of
      symptoms to hospital admission, we can make rapid evaluation and surgical
      intervention to reduce the morbidity and mortality of obturator hernia.

PMID- 20057281
TI  - Ischemic gastropathy: an unusual cause of abdominal pain and gastric ulcers.
AB  - Chronic mesenteric ischemia classically presents as "intestinal angina" with
      generalized postprandial abdominal pain lasting up to 3 hours. Over time, these
      episodes can become much more intense and ultimately lead to sitophobia with
      significant weight loss. Symptoms are not specific and often mistakenly
      attributed to other gastrointestinal etiologies such as peptic ulcer disease.
      Gastric ulcerations as a direct result of mesenteric ischemia have been reported
      but are relatively rare because of the rich collateral blood supply to the
      stomach. Therefore, a diagnosis of ischemic gastropathy is seldom entertained in
      patients presenting with abdominal pain and gastric ulcers.

PMID- 20057282
TI  - Just what do we mean by clinical significance.

PMID- 20057284
TI  - Proteomics-based approach identified differentially expressed proteins with
      potential roles in endometrial carcinoma.
AB  - INSTRUCTION: We used proteomic approaches to identify altered expressed proteins
      in endometrial carcinoma, with the aim of discovering potential biomarkers or
      therapeutic targets for endometrial carcinoma. METHODS: The global proteins
      extracted from endometrial carcinoma and normal endometrial tissues were
      separated by 2-dimensional electrophoresis and analyzed with PDQuest (Bio-Rad,
      Hercules, Calif) software. The differentially expressed spots were identified by
      mass spectrometry and searched against NCBInr protein database. Those proteins
      with potential roles were confirmed by Western blotting and immunohistochemical
      assays. RESULTS: Ninety-nine proteins were identified by mass spectrometry, and a
      cluster diagram analysis indicated that these proteins were involved in
      metabolism, cell transformation, protein folding, translation and modification,
      proliferation and apoptosis, signal transduction, cytoskeleton, and so on. In
      confirmatory immunoblotting and immunohistochemical analyses, overexpressions of
      epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A were also
      observed in endometrial carcinoma tissues, which were consistent with the
      proteomic results. CONCLUSIONS: Our results suggested that these identified
      proteins, including epidermal fatty acid-binding protein, calcyphosine, and
      cyclophilin A, might be of potential values in the studies of endometrial
      carcinogenesis or investigations of diagnostic biomarkers or treatment targets
      for endometrial carcinoma.

PMID- 20057285
TI  - Abdominal wall metastases in patients with ovarian cancer after laparoscopic
      surgery: incidence, risk factors, and complications.
AB  - OBJECTIVES: Laparoscopy is the standard procedure to clarify undefined ovarian
      masses. However, laparoscopy could induce tumor spread in ovarian cancer (OC).
      The aim of this study was to assess the incidence, the risk factors, and the
      complications of abdominal wall metastases (AWM) in patients with OC after
      laparoscopy. METHODS: Retrospective study of patients with primary diagnosis of
      OC who had laparoscopy before cytoreductive surgery and resected port sites in
      laparotomy between 1999 and 2008 at our institution. Patients with borderline or
      nonepithelial ovarian tumors were excluded. RESULTS: Of 537 patients with a first
      diagnosis of OC, 101 had laparoscopy before definitive operation after a median
      of 31 days. Histological examination at final cytoreductive surgery of the port
      sites was conducted in 66 patients, whereas 31 patients (47%) showed AWM.
      Patients experiencing AWM had higher tumor stages and peritoneal carcinomatosis.
      Ascites with more than 500 mL was a further independent risk factor for AWM (odds
      ratio: 7.2; 95% confidence interval, 1.5-35.8; P = 0.016). Abdominal wall
      metastasis did not impact on survival in our cohort; however, affected patients
      showed significant larger abdominal wall resections (mean [SD]): 41.0 (angled
      brace 13.1) cm versus 9.1 (angled brace 1.4) cm in comparison with patients
      without AWM (P = 0.013), and 2 patients developed abdominal wall recurrences.
      CONCLUSIONS: The incidence of AWM in patients experiencing OC was considerably
      high when laparoscopic surgery was conducted before cytoreductive surgery.
      Patients experiencing AWM seem to have more surgical burden. However, our series
      did not show a dramatic impact of AWM on long-term outcome. Patients with highly
      suspected advanced OC and ascites with more than 500 mL should be referred
      directly to a gynecologic oncologist who is able to balance risks of laparoscopic
      staging and direct cytoreductive surgery.

PMID- 20057286
TI  - The expression of H3K9Ac, H3K14Ac, and H4K20TriMe in epithelial ovarian tumors
      and the clinical significance.
AB  - OBJECTIVE: To study the expression of acetylation of histone H3 Lys9, Lys14
      (H3K9Ac, H3K14Ac), and trimethylation of histone H4 Lys20 (H4K20TriMe) in ovarian
      epithelial tumors and the relation with histological grading and clinical
      staging. METHODS: The mean optical density of H3K9Ac, H3K14Ac, and H4K20TriMe of
      normal ovarian epithelium, ovarian adenomas, ovarian borderline tumors, and
      ovarian epithelial carcinomas was determined by immunohistochemistry, and the
      relation with histological grading and clinical staging was analyzed. RESULTS: As
      the malignancy of ovarian epithelial tumors increased, the expression of H3K9Ac
      and H4K20TriMe significantly decreased (P < 0.05). Although the expressing
      difference of H3K14Ac was without statistical significance in each group (P >
      0.05), there were no differences in the expression of H3K9Ac, H3K14Ac, and
      H4K20TriMe in serous cystadenomas, borderline serous cystadenomas, and mucinous
      cystadenomas (P > 0.05). Compared with mucinous cystadenocarcinomas, the
      expression of H3K9Ac and H4K20TriMe in serous cystadenocarcinomas was lower (P <
      0.05). Although there was no difference of H3K14Ac expression in serous and
      mucinous cystadenocarcinomas (P > 0.05), as the histological grade reduced, the
      expression of H3K9Ac and H4K20TriMe reduced (P < 0.05), and it was lower in the
      late clinical stage than those in the earlier stage (P < 0.01). CONCLUSIONS: The
      decreasing of H3K9Ac and H4K20TriMe is possibly related with the occurrence of
      epithelial ovarian tumors. The more significant the expression of H3K9Ac and
      H4K20TriMe was, the lower the histological grading and the later the clinical
      staging were. H3K9Ac and H4K20TriMe were potential biomarkers for prognosis.
      H3K14Ac showed no significant relation with the occurrence and development of
      ovarian tumors.

PMID- 20057287
TI  - Cisplatin-based radiochemotherapy improves the negative prognosis of c-erbB-2
      overexpressing advanced cervical cancer.
AB  - OBJECTIVES: To determine the impact of c-erb-B2 overexpression on disease-free
      survival (DFS) and local relapse in patients with advanced cervical cancer (CC)
      receiving concurrent chemoradiotherapy treatment. METHODS: A total of 136
      patients with advanced CC (FIGO stage: IB2-IIA [12]; IIB [34]; IIIB [71]; IVA
      [19]; including both epidermoid [86] and adenocarcinoma [14]) were analyzed to
      determine c-erb-B2 levels by immunohistochemistry (c-erb-B2 antibody; Dako,
      Glostrup, Denmark). Only c-erb-B2+++ biopsies were considered positive. All
      patients received pelvic radiotherapy, brachytherapy, and concurrent chemotherapy
      with 2 different regimens: 48 patients were treated with tegafur (800 mg/d
      orally) and 88 with tegafur (same doses) plus 5 cycles of weekly cisplatin 40
      mg/m/wk intravenously. RESULTS: A total of 32 (23.5%) biopsies were considered c
      erb-B2-positive. Three-year and 5-year DFS were 61% and 58% for c-erb-B2-negative
      patients and 36% and 36% for c-erB2-positive patients, respectively (P = 0.02).
      Patients were stratified in 4 groups according to their c-erb-B2 status and
      whether they received cisplatin. The group of patients with c-erb-B2
      overexpression that did not receive platinum treatment had a higher rate of
      pelvic relapse (P < 0.0001), associated with a decreased DFS (P = 0.0014).
      CONCLUSIONS: c-erb-B2 overexpression may imply a poor prognosis for patients with
      advanced CC. Treatment with cisplatin-based radiochemotherapy improved outcome in
      these patients.

PMID- 20057288
TI  - "Differentiated-type vulval intraepithelial neoplasia has a high-risk association
      with vulval squamous cell carcinoma".

PMID- 20057290
TI  - Significant advances in cataract and refractive surgery over the last decade.
      Preface.

PMID- 20057291
TI  - Approaching cataract surgery in patients with fuchs' endothelial dystrophy.

PMID- 20057292
TI  - Cataract and refractive surgery in herpetic eye disease.

PMID- 20057293
TI  - Eyelid malposition after cataract and refractive surgery.

PMID- 20057294
TI  - Pathophysiology of postoperative diplopia after cataract surgery.

PMID- 20057295
TI  - Intraocular lens implantation in penetrating ocular trauma.

PMID- 20057296
TI  - Selection of intraocular lenses in patients with uveitis.

PMID- 20057297
TI  - Pediatric intraocular lens implantation: historic perspective and current
      practices.

PMID- 20057298
TI  - Pseudoexfoliation syndrome and cataract surgery.

PMID- 20057299
TI  - Combined cataract and glaucoma surgeries: traditional and new combinations.

PMID- 20057300
TI  - Accommodating intraocular lenses: theory and practice.

PMID- 20057301
TI  - Phakic intraocular lenses.

PMID- 20057302
TI  - Perioperative evaluation and management of cataract surgery in uveitis patients.

PMID- 20057303
TI  - Pseudophakic cystoid macular edema.

PMID- 20057304
TI  - Progression of diabetic retinopathy and maculopathy after phacoemulsification
      surgery.

PMID- 20057305
TI  - Management of traumatic crystalline lens subluxation and dislocation.

PMID- 20057306
TI  - Intraocular lens calculations after corneal refractive surgery.

PMID- 20057308
TI  - Emergence and persistence of nevirapine resistance in breast milk after single
      dose nevirapine administration.
AB  - OBJECTIVE: Single-dose nevirapine (NVP) (sdNVP) can reduce the risk of HIV
      vertical transmission. We assessed risk factors for NVP resistance in plasma and
      breast milk from sdNVP-exposed Ugandan women. METHODS: Samples were analyzed
      using the Roche AMPLICOR HIV-1 Monitor Test Kit, version 1.5, and the ViroSeq HIV
      1 Genotyping System. NVP concentrations were determined by liquid chromatography
      with tandem mass spectroscopy. RESULTS: HIV genotypes (plasma and breast milk)
      were obtained for 30 women 4 weeks after sdNVP (HIV subtypes: 15A, 1C, 12D, two
      recombinant). NVP resistance was detected in 12 (40%) of 30 breast milk samples.
      There was a nonsignificant trend between detection of NVP resistance in breast
      milk and plasma (P = 0.06). There was no association of HIV resistance in breast
      milk with median maternal pre-NVP viral load or CD4 cell count, median breast
      milk viral load at 4 weeks, breast milk sodium more than 10 mmol/l, HIV subtype,
      or concentration of NVP in breast milk or plasma. CONCLUSION: NVP resistance was
      frequently detected in breast milk 4 weeks after sdNVP exposure. In this study,
      we were unable to identify specific factors associated with breast milk NVP
      resistance.

PMID- 20057310
TI  - Etravirine resistance associated mutations in HIV-infected patients failing
      efavirenz or nevirapine in the Spanish antiretroviral resistance database.
AB  - The prevalence of etravirine resistance mutations was examined in genotypes
      derived from 1343 HIV-infected patients failing nevirapine or efavirenz in the
      resistance database of the Spanish AIDS Research Network (ResRIS). Overall,
      etravirine-resistant genotypes were recognized in 18.7% of patients, with no
      significant differences between failures under nevirapine or efavirenz. Thus,
      more than 80% patients with prior failure to nonnucleoside reverse transcriptase
      inhibitors could potentially benefit from etravirine rescue therapy.

PMID- 20057309
TI  - The effects of intermittent, CD4-guided antiretroviral therapy on body
      composition and metabolic parameters.
AB  - OBJECTIVE: To assess the effects of decreased antiretroviral therapy exposure on
      body fat and metabolic parameters. DESIGN: Substudy of the Strategies for
      Management of Anti-Retroviral Therapy study, in which participants were
      randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to
      continuous [Viral Suppression (VS) group] antiretroviral therapy. METHODS:
      Participants at 33 sites were coenrolled in the Strategies for Management of Anti
      Retroviral Therapy Body Composition substudy. Regional fat was assessed annually
      by whole-body dual-energy X-ray absorptiometry and abdominal computed tomography.
      Fasting metabolic parameters were assessed at months 4, 8, and annually.
      Treatment groups were compared for changes in fat and metabolic markers using
      longitudinal mixed models. RESULTS: Two hundred and seventy-five patients were
      randomized to the DC (n = 142) or VS (n = 133) group and followed for a median of
      2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval
      3.5-16.1; P = 0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm,
      95% confidence interval -0.1 to 28.7; P = 0.05) increased in the DC group. There
      was no treatment difference in visceral abdominal fat (DC-VS difference -2.1%,
      95% confidence interval -13.5 to 9.4; P = 0.72). Lipids significantly decreased
      in the DC group by month 4 and treatment differences persisted throughout follow
      up (P < or = 0.001). By 12 months, hemoglobin A1C increased in the DC (+0.3%) and
      remained stable in the VS group (P = 0.003); the treatment difference remained
      significant throughout follow-up (P = 0.02). CONCLUSION: After 12 months,
      intermittent antiretroviral therapy increased subcutaneous fat, had no effect on
      visceral abdominal fat, decreased plasma lipids, and increased hemoglobin A1C
      compared with continuous antiretroviral therapy.

PMID- 20057311
TI  - Seven-year experience of a primary care antiretroviral treatment programme in
      Khayelitsha, South Africa.
AB  - OBJECTIVES: We report on outcomes after 7 years of a community-based
      antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death
      registry linkages to correct for mortality under-ascertainment. DESIGN: This is
      an observational cohort study. METHODS: Since inception, patient-level clinical
      data have been prospectively captured on-site into an electronic patient
      information system. Patients with available civil identification numbers who were
      lost to follow-up were matched with the national death registry to ascertain
      their vital status. Corrected mortality estimates weighted these patients to
      represent all patients lost to follow-up. CD4 cell count outcomes were reported
      conditioned on continuous virological suppression. RESULTS: Seven thousand, three
      hundred and twenty-three treatment-naive adults (68% women) started ART between
      2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006.
      Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died.
      Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9-24.3).
      Mortality fell over time as patients accessed care earlier (median CD4 cell count
      at enrolment increased from 43 cells/microl in 2001 to 131 cells/microl in 2006).
      Patients who remained virologically suppressed continued to gain CD4 cells at 5
      years (median 22 cells/microl per 6 months). By 5 years, 14.0% of patients had
      failed virologically and 12.2% had been switched to second-line therapy.
      CONCLUSION: At a time of considerable debate about future global funding of ART
      programmes in resource-poor settings, this study has demonstrated substantial and
      durable clinical benefits for those able to access ART throughout this period, in
      spite of increasing loss to follow-up.

PMID- 20057313
TI  - Performance of anal cytology in a clinical setting when measured against
      histology and high-resolution anoscopy findings.
AB  - OBJECTIVES: The success of cervical cytology in screening for cervical neoplasia
      has led to the concept of anal cytology screening for anal neoplasia. Our
      objective is to study the performance of anal cytology as a screening tool.
      DESIGN: We assessed anal cytology against histology and high-resolution anoscopy
      in a clinical setting. METHODS: Anal pap test was obtained prior to high
      resolution anoscopy examinations and biopsies. The results were analysed against
      a number of patient variables. RESULTS: From 395 individuals (93% men), 584 anal
      pap tests were obtained. HIV status was positive in 212 (54%) and negative in 156
      (39%) individuals. On the basis of 288 histology results, the sensitivity of anal
      cytology to detect disease was 70% [95% confidence interval (CI) 64-75], whereas
      the specificity was 67% (95% CI 38-88). For high-grade disease (anal
      intraepithelial neoplasia 2/3), sensitivity of anal cytology was 81% (95% CI 70
      90), and the negative predictive value was 85% (95% CI 76-92). Sensitivity was
      dependent on the area of disease (86% for two or more quadrants vs. 69% for one
      or more quadrants, P = 0.002) and HIV positivity (76% in HIV positive vs. 59% in
      HIV negative, P = 0.009). Amongst HIV-positive patients, the sensitivity was 90%
      when CD4 cell count was 400 cells/microl or less compared with 67% when CD4 cell
      count was above 400 cells/microl (P = 0.005). CONCLUSION: Anal cytology performs
      similar to cervical cytology in a clinical setting. Sensitivity of anal smear is
      dependent on the area (quadrants) of disease present. Sensitivity of anal
      cytology is enhanced when CD4 cell count is less than 400 cells/microl in HIV
      positive men. Our results may explain the variable sensitivity reported in the
      literature.

PMID- 20057312
TI  - Late diagnosis in the HAART era: proposed common definitions and associations
      with mortality.
AB  - OBJECTIVE: To identify a definition of presentation after clinical or
      immunological disease progression that will reliably identify an individual at
      high risk of mortality over the first 3 months after HIV diagnosis and that can
      be adopted as a basis for comparing over time and regions. DESIGN: An
      observational cohort study. METHODS: Individuals seen for the first time at a UK
      Collaborative HIV Cohort study clinic from 1996 to 2006 were identified. Two
      immunological (CD4 cell count < 200 cells/microl and CD4 cell count <50
      cells/microl) and two clinical (AIDS and severe/moderate AIDS) criteria for
      presentation with advanced HIV disease were compared, as well as combinations of
      them. The predictive ability of each diagnosis for identifying individuals who
      died in the first 3 months after HIV diagnosis was assessed. RESULTS: Fifteen
      thousand seven hundred and seventy-four patients were included, of whom 1495
      (9.5%), 4231 (26.8%), 1523 (9.7%) and 379 (2.4%) had a CD4 cell count below 50
      cells/microl, CD4 cell count below 200 cells/microl, AIDS or severe/moderate AIDS
      at diagnosis; CD4 cell counts were unavailable for 2264 (14.4%) patients. Two
      hundred and six (1.3%) patients died within the first 3 months. Sensitivities of
      the individual criteria ranged from 18.0% (severe/moderate AIDS) to 50.5% (CD4
      cell count < 200 cells/microl) with specificities ranging from 73.5% (CD4 < 200
      cells/microl) to 97.8% (severe/moderate AIDS). Combinations of clinical and
      immunological criteria increased the sensitivity but decreased the specificity.
      CONCLUSION: We propose that presentation with 'advanced HIV disease' is
      presentation with a CD4 cell count below 200 cells/microl or AIDS, whereas 'late'
      presentation is defined as presentation when the CD4 cell count is below that
      when treatment should be initiated (currently CD4 cell count < 350 cells/microl
      or AIDS).

PMID- 20057314
TI  - Redefining outcome measures in schizophrenia: integrating social and clinical
      parameters.
AB  - PURPOSE OF REVIEW: Schizophrenia is a complex neurobehavioral disorder for which
      there are many promising new treatments. There is, however, a discrepancy in
      outcome measure reports when they are obtained from patients, relatives,
      caregivers, or professionals, making it difficult to determine the level of
      recovery. This lack of agreement may result from limitations of the measurement
      tools themselves, which are not comprehensive and may be measuring different
      aspects of outcome. Alternatively, it could be that the conceptual understanding
      of outcome and recovery require development. RECENT FINDINGS: For various
      reasons, patients assessed as 'recovered' remain excluded from mainstream
      society. We are of the opinion that present outcome measures do not capture real
      life situations. We propose that the concept of recovery be carefully defined and
      the gold standard of outcome should incorporate social and clinical parameters.
      We attempt to redefine recovery. Patients who have shown clinical improvement do
      not necessarily do well in everyday situations even though there is obvious
      clinical improvement. Therefore, it has been repeatedly argued that a consensus
      of recovery should be determined and that routine clinical practice should then
      adapt to the agreed criteria. SUMMARY: We argue that the outcome measures should
      be multidimensional and consist of at least two parameters: clinical remission
      and social outcome.

PMID- 20057315
TI  - Behavioral medicine interventions in diabetes.
AB  - PURPOSE OF REVIEW: Poor glycemic control is prevalent in the majority of patients
      with diabetes and has a strong impact on medical as well as psychological
      outcomes. Psychological and behavioral variables are of particular interest, as
      the patients themselves are the most determining factor of treatment success.
      Consequently, a wide range of behavioral medicine interventions are aimed at
      improvement in diabetes self-management, coping strategies, blood glucose
      awareness, and stress reduction. This review provides an overview of randomized
      controlled trials (RCTs) published in the past 18 months (from March 2008 to
      September 2009) that evaluated behavioral medicine interventions in patients with
      diabetes. The review summarizes the interventions' effects on metabolic control
      and other medical variables, as well as diabetes self-management and
      psychological outcomes. RECENT FINDINGS: Behavioral medicine interventions in the
      diabetes field encompass a number of different approaches with the goal of
      improving medical outcomes such as glycemic control as well as psychological
      outcomes. There is evidence for beneficial effects of recent behavioral medicine
      treatments in terms of improvement of metabolic control as indicated by decreased
      glycated hemoglobin (HbA1c). Furthermore, positive effects were observed
      regarding diabetes-related self-efficacy, self-management, proactive coping, and
      the reduction of psychological burdens and symptoms. SUMMARY: Behavioral medicine
      interventions are effective in diabetes treatment, especially in patients with a
      high level of diabetes-related distress, difficulty in coping, or insufficient
      blood glucose awareness.

PMID- 20057316
TI  - Impact of limited population diversity of genome-wide association studies.
AB  - The article describes the limited population diversity of genome-wide association
      studies and its resulting impact on the development of commercial genetic tests
      with restricted applicability and usefulness to certain groups, potentially
      increasing existing disparities. To enable development of new clinical tools
      applicable to all groups, much more focus is needed to engage minority
      communities to enroll in genetics or genomic research studies and on
      investigators to reach out to underrepresented communities.

PMID- 20057317
TI  - Perspectives and diagnostic considerations in spinal muscular atrophy.
AB  - Spinal muscular atrophy is an autosomal recessive neurodegenerative disease and
      the most common genetic cause of infant mortality. The disease results in motor
      neuron loss and skeletal muscle atrophy. Spinal muscular atrophy is caused by
      mutations in the telomeric copy of the survival motor neuron 1 (SMN1) gene, but
      all patients retain a centromeric copy of the gene, SMN2. In the majority of
      cases, the disease severity correlates inversely with an increased SMN2 gene copy
      number. Because spinal muscular atrophy is both a severe and common disorder, a
      direct carrier testing has been beneficial to many families. The survival motor
      neuron protein is ubiquitously expressed and performs a role in the assembly of
      the spliceosome. It is still not understood why mutations in the SMN1 gene only
      seem to affect motor neurons. Progress has been made by developing therapeutic
      strategies based on understanding the pathogenesis of the disease. This review
      attempts to highlight some of the recent advances in the understanding of the
      disease with a focus on molecular diagnostics.

PMID- 20057318
TI  - Diffusion-weighted magnetic resonance imaging of the liver using tracking only
      navigator echo: feasibility study.
AB  - PURPOSE: To introduce and assess the TRacking Only Navigator echo (TRON)
      technique for diffusion-weighted magnetic resonance imaging (DWI) of the liver.
      SUBJECTS AND METHODS: A total of 10 volunteers underwent TRON, respiratory
      triggered (RT), and free breathing (FB) DWI of the liver. Scan times of TRON and
      RT DWI were measured, and image sharpness in TRON, RT, and FB DWI was assessed
      and compared using nonparametric tests. Furthermore, 14 patients with liver
      metastasis who had undergone TRON and RT DWI of the liver were retrospectively
      assessed. Relative contrast ratios (RCRs) and apparent diffusion coefficients
      (ADCs) of the largest hepatic metastasis in TRON and RT DWI were measured. RCRs
      were compared using a parametric test and agreement in ADCs was assessed using
      the Bland-Altman method. RESULTS: In the volunteers, mean scan times of TRON and
      RT relative to FB DWI were 110% to 112% and 261% to 290%, respectively. On axial
      images, there were no significant differences in images sharpness among TRON, RT,
      and FB DWI, but on coronal images image sharpness in TRON was nearly always
      significantly better (P < 0.05) than in RT and FB DWI. In the patients, mean RCRs
      between TRON and RT DWI were not significantly different (P = 0.9091). Mean
      difference in ADC +/- limits of agreement (in 10 mm/s) between TRON and RT DWI
      was -0.16 +/- 0.79. CONCLUSION: TRON offers sharp diffusion-weighted images of
      the liver using an efficient scan time, making it an excellent alternative to RT
      and FB DWI. The moderate to poor agreement in ADCs of liver metastases between
      TRON and RT DWI requires further investigation.

PMID- 20057319
TI  - Gadoxetic acid-enhanced magnetic resonance imaging for differentiating small
      hepatocellular carcinomas (< or =2 cm in diameter) from arterial enhancing
      pseudolesions: special emphasis on hepatobiliary phase imaging.
AB  - OBJECTIVES: To determine the characteristic enhancing features of hepatocellular
      carcinoma (HCC) and arterial-enhancing pseudolesion (AEP) on gadoxetic acid
      (Primovist)-enhanced magnetic resonance imaging (MRI) and to assess its
      performance compared with that of multirow detector computed tomography (MDCT)
      for differentiating small HCC (< or =2 cm in diameter) from AEP in cirrhotic
      liver. MATERIALS AND METHODS: A total of 69 patients with 97 small, arterial
      enhancing hepatic lesions (0.5-2 cm in diameter), ie, 44 HCCs and 53 AEPs,
      detected on gadoxetic acid-enhanced MRI, were included in this study. HCCs were
      diagnosed either through histopathology confirmation (n = 16) or by a combination
      of liver computed tomography (CT), angiographic findings, lipiodol CT, and AFP
      levels (n = 28). AEPs were diagnosed either through histopathology confirmation
      (n = 2) or were based on the angiographic findings, liver CT, and follow-up
      imaging (n = 51). Two radiologists jointly analyzed the morphologic features and
      the enhancement characteristics on the gadoxetic acid-enhanced MRI. Of the 69
      study patients, 42 patients with 60 arterial enhancing lesions underwent
      quadruple-phase CT in addition to their MRI examination within 4 weeks before or
      after the MRI, and 2 other radiologists who were blinded to the final diagnosis
      independently reviewed the MRI and CT images in random order, at an interval of 2
      weeks. Diagnostic performance was evaluated using receiver operating
      characteristics. The Kappa test was used to evaluate interobserver agreement.
      RESULTS: Among 44 HCCs, 42 (95.4%) demonstrated low signal intensity (SI) and
      only 2 showed iso- or high SI on the hepatobiliary phase of gadoxetic acid
      enhanced MRI. Alternatively, most AEPs showed iso SI on the hepatobiliary (n =
      50, 94.3%) phase, and only 2 AEPs showed low SI. Compared with the diagnostic
      performance of the 2 imaging modalities, the mean areas under the receiver
      operator characteristic curves on MR imaging were 0.975 for reviewer 1 and 0.966
      for reviewer 2, whereas those of CT imaging were 0.892 for reviewer 1 and 0.888
      for reviewer 2 (P = 0.069 and P = 0.106, respectively). The sensitivity for each
      reviewer with MR imaging (93.9% and 90.9%, respectively) was significantly higher
      than that with multiphasic CT (54.5%, in both) (P = 0.001 and 0.0018,
      respectively). CONCLUSION: HCCs and AEPs show different enhancing features on the
      delayed dynamic and hepatobiliary phases of gadoxetic acid-enhanced MRI.
      Gadoxetic acid-enhanced MRI may, therefore, help to differentiate between HCC and
      AEP.

PMID- 20057320
TI  - Sex with older partners is associated with primary HIV infection among men who
      have sex with men in North Carolina.
AB  - BACKGROUND: Studies from the 1990s suggested sex with older partners was
      associated with HIV infection. We evaluated the hypothesized association between
      primary HIV infection (PHI) and having older sexual partners among men who have
      sex with men (MSM). METHODS: MSM with PHI and HIV-uninfected MSM completed audio
      computer-assisted self-interviews exploring behaviors involving their 3 most
      recent sexual partners before enrollment (if uninfected) or diagnosis (if PHI).
      RESULTS: Of 74 men reporting any lifetime sex with men, 20 had PHI (27%).
      Demographics (including age) were similar between groups; 39% were non-white and
      74% identified as gay. The mean age of sex partners differed significantly: men
      with PHI had partners on average 6 years older than themselves, whereas
      uninfected men's partners were 4 months their junior (P < 0.001). After adjusting
      for race, sex while intoxicated, and having a serodiscordant/serostatus unknown
      partner, a participant had twice the odds of PHI if his sex partner was 5 years
      his senior (odds ratio 2.0, 95% confidence interval: 1.2 to 3.3). CONCLUSIONS:
      Among a sample of young MSM, the odds of HIV infection increased significantly as
      the age of sexual partners increased. These findings can inform behavioral
      interventions in communities of at-risk MSM and secondary prevention efforts
      among those already living with HIV.

PMID- 20057321
TI  - Thrombotic complications of tunneled central lines in children with malignancy.
AB  - BACKGROUND: The total rate of thrombotic complications caused by tunneled central
      lines (TCL) is still not known, as are the long-term consequences. AIM OF THE
      STUDY: Estimation of a rate of thrombotic complications in children with TCL and
      malignancy and Doppler ultrasound assessment of blood flow after TCL removal.
      MATERIALS AND METHODS: One hundred twenty-four children were enrolled for the
      study. Heparin lock was used as a prophylaxis for line occlusion. The rate and
      type of thrombotic events associated with TCL were analyzed in all patients. In
      children without an earlier history of thrombosis, a Doppler ultrasound
      examination was carried out after TCL removal. RESULTS: In 45.2% of patients at
      least 1 thrombotic event occurred. These events were TCL lumen thrombosis (42.8%
      of patients) and subclavian vein thrombosis (2.4% of patients). In 37 patients
      Doppler ultrasound was carried out and revealed an abnormal blood flow in the
      vein that was examined in 59.5% of them. CONCLUSIONS: The total rate of
      thrombotic complications in children with TCL and malignancy is high. A
      substantial proportion of thrombotic complications can be clinically silent. The
      use of a heparin lock once a week seems far from effective in preventing
      thrombotic events in patients with TCL. The TCL life span has no influence on the
      rate of thrombotic events.

PMID- 20057322
TI  - Pancreatoblastoma: two case reports from a medical center in Taiwan.
AB  - Although pancreatoblastoma (PB) is an extremely rare tumor, it is the most common
      pancreatic tumor in children. We reported 2 cases of PB treated at a medical
      center in Taiwan. One was a 3.5-year-old boy who presented with abdominal pain.
      Physical examination demonstrated abdominal masses. Multiple pancreatic and
      hepatic masses were noted by magnetic resonance imaging. He underwent surgical
      resection but tumor could not be removed completely, which was confirmed by the
      pathology. He received chemotherapy consisting of cisplatin and doxorubicin after
      the surgery but the tumor progressed rapidly. He died of progressive disease and
      sepsis. The other case was a 4-year-old boy presented with abdominal pain.
      Computed tomography showed pancreatic tumor. He underwent surgical resection and
      pathology showed PB. He received chemotherapy after complete tumor resection. He
      is disease free till now. Complete tumor resection is the major difference of
      these 2 patients and is the most important factor affecting the outcome.

PMID- 20057323
TI  - Juvenile dermatomyositis as a paraneoplastic phenomenon: an update.
AB  - Approximately 33% of adult patients with dermatomyositis develop malignancy with
      up to 42% presenting after the diagnosis has been made; careful evaluation for
      malignancy is often undertaken at the time of dermatomyositis diagnosis. This
      phenomenon has rarely been noted in pediatric patients and extensive workup for
      malignancy is not indicated in pediatric patients. In 1993, 6 cases were reported
      in which juvenile dermatomyositis/polymyositis (JDM/PM) appeared to be part of a
      paraneoplastic phenomenon. Our objective was to update the literature for
      reported cases of malignancy associated with JDM/PM; we reviewed the literature
      over the last 15 years and located 6 additional cases. In 9 of 12 reported
      patients an unusual physical finding such as splenomegaly or lymphadenopathy was
      noted at the time of diagnosis, and in the entire group, the malignancy occurred
      within a mean of 12 months. It is less likely that JDM/PM in pediatric patients
      is a paraneoplastic phenomenon as it is in adult patients. However, if the
      physical examination at the time of diagnosis of JDM/PM is atypical the presence
      of malignancy must be considered and a more in-depth evaluation to rule out
      malignancy should be performed prior to the initiation of treatment.

PMID- 20057324
TI  - Clofarabine-induced capillary leak syndrome in a child with refractory acute
      lymphoblastic leukemia.
AB  - Clofarabine has significant efficiency in children with relapsed or refractory
      leukemia. In previous pediatric trials, various adverse effects have been
      described. In this case, we report a child with refractory acute lymphoblastic
      leukemia who developed fatal capillary leak syndrome during clofarabine therapy.

PMID- 20057325
TI  - Small cell ovarian carcinoma: a rare, aggressive tumor masquerading as
      constipation in a teenager with a fatal outcome.
AB  - SUMMARY: A 16-year-old female presented with symptoms consistent with
      constipation with no constitutional symptoms. Multiple different laxatives were
      attempted over 4 months and were unsuccessful. This thin female developed an
      impressively distended, nonacute abdomen within a 2-week period. Histology
      demonstrated a stage IV small cell carcinoma of the ovary. Her disease initially
      responded to treatment, but ultimately she relapsed and failed to respond to 2
      other chemotherapy combinations, which were based on limited success found in the
      literature. She ultimately passed away 13 months after the diagnosis,
      demonstrating the poor prognosis and rapid spread of this rare disease.

PMID- 20057326
TI  - Do financial barriers to healthcare services affect health status?

PMID- 20057327
TI  - Using more end-of-life homecare services is associated with using fewer acute
      care services: a population-based cohort study.
AB  - BACKGROUND: Healthcare systems are investing in end-of-life homecare to reduce
      acute care use. However, little evidence exists on the timing and amount of
      homecare services necessary to reduce acute care utilization. OBJECTIVES: To
      investigate whether admission time to homecare and the amount of services, as
      measured by average nursing and personal support and homemaking (PSH) hours/week
      (h/wk), are associated with using acute care services at end-of-life. RESEARCH
      DESIGN: Retrospective observational cohort study. SUBJECTS: Decedents admitted to
      end-of-life homecare in Ontario, Canada. MEASURES: The odds ratios (OR) of having
      a hospitalization or emergency room visit in the 2 weeks before death and dying
      in a hospital. RESULTS: The cohort (n = 9018) used an average of 3.11 (SD = 4.87)
      nursing h/wk, 3.18 (SD = 6.89) PSH h/wk, and 18% were admitted to homecare for <1
      month. As admission time to death and homecare services increased, the adjusted
      OR of an outcome decreased in a dose response manner. Patients admitted earlier
      than 6 months before death had a 35% (95% CI: 25%-44%) lower OR of
      hospitalization than those admitted 3 to 4 weeks before death; patients using
      more than 7 nursing h/wk and more than 7 PSH h/wk had a 50% (95% CI: 37%-60%) and
      35% (95% CI: 21%-47%) lower OR of a hospitalization, respectively, than patients
      using 1 h/wk, controlling for other covariates. Other outcomes had similar
      results. CONCLUSION: These results suggest that early homecare admission and
      increased homecare services will help alleviate the demand for hospital resources
      at end-of-life.

PMID- 20057328
TI  - Is survival better at hospitals with higher "end-of-life" treatment intensity?
AB  - BACKGROUND: Concern regarding wide variations in spending and intensive care unit
      use for patients at the end of life hinges on the assumption that such treatment
      offers little or no survival benefit. OBJECTIVE: To explore the relationship
      between hospital "end-of-life" (EOL) treatment intensity and postadmission
      survival. RESEARCH DESIGN: Retrospective cohort analysis of Pennsylvania Health
      Care Cost Containment Council discharge data April 2001 to March 2005 linked to
      vital statistics data through September 2005 using hospital-level correlation,
      admission-level marginal structural logistic regression, and pooled logistic
      regression to approximate a Cox survival model. SUBJECTS: A total of 1,021,909
      patients > or =65 years old, incurring 2,216,815 admissions in 169 Pennsylvania
      acute care hospitals. MEASURES: EOL treatment intensity (a summed index of
      standardized intensive care unit and life-sustaining treatment use among patients
      with a high predicted probability of dying [PPD] at admission) and 30- and 180
      day postadmission mortality. RESULTS: There was a nonlinear negative relationship
      between hospital EOL treatment intensity and 30-day mortality among all
      admissions, although patients with higher PPD derived the greatest benefit.
      Compared with admission at an average intensity hospital, admission to a hospital
      1 standard deviation below versus 1 standard deviation above average intensity
      resulted in an adjusted odds ratio of mortality for admissions at low PPD of 1.06
      (1.04-1.08) versus 0.97 (0.96-0.99); average PPD: 1.06 (1.04-1.09) versus 0.97
      (0.96-0.99); and high PPD: 1.09 (1.07-1.11) versus 0.97 (0.95-0.99),
      respectively. By 180 days, the benefits to intensity attenuated (low PPD: 1.03
      [1.01-1.04] vs. 1.00 [0.98-1.01]; average PPD: 1.03 [1.02-1.05] vs. 1.00 [0.98
      1.01]; and high PPD: 1.06 [1.04-1.09] vs. 1.00 [0.98-1.02]), respectively.
      CONCLUSIONS: Admission to higher EOL treatment intensity hospitals is associated
      with small gains in postadmission survival. The marginal returns to intensity
      diminish for admission to hospitals above average EOL treatment intensity and
      wane with time.

PMID- 20057329
TI  - What factors affect the productivity and efficiency of physician practices?
AB  - BACKGROUND: Increasing the productivity and efficiency of physician practices
      could help relieve the rapid growth of US healthcare costs and the expected
      physician shortage. Radiology practices are an attractive specific focus for
      research on practices' productivity and efficiency because they are home to many
      purportedly productivity-enhancing operational technologies. This affords an
      opportunity to study the effect of production technology on physicians' output.
      As well, radiology is a leader in the general movement of physicians out of very
      small practices. And imaging is by the fastest-growing category of physician
      expenditure. RESEARCH DESIGN: Using data from 2003 to 2007 surveys of
      radiologists, we estimate a stochastic frontier model to study the effects of
      practice characteristics, such as work hours, practice size, and output mix, and
      technologies used in work production, on practices' productivity and efficiency.
      RESULTS: At the mean, the elasticities of output with respect to practice size
      and annual hours worked per full-time physician were 0.73 and 0.51, respectively.
      Some production technologies increase productivity by 15% to 20%; others generate
      no increase. Using "nighthawks"--ie, contracting out after-hours work to external
      firms that consolidate workflow--significantly increases practice efficiency.
      CONCLUSIONS: The general US trend toward larger practice size is unlikely to
      relieve cost or physician shortage pressures. The actual effect of purportedly
      productivity-enhancing operational technologies needs to be carefully evaluated
      before they are widely adopted. As the recently-developed innovations of
      nighthawks and hospitalists show, practices should give more attention to a
      possible choice to "buy," rather than "make," part of their output.

PMID- 20057330
TI  - Meaningful variation in performance: what does variation in quality tell us about
      improving quality?
AB  - BACKGROUND: Variance reduction is sometimes considered as a goal of clinical
      quality improvement. Variance among physicians, hospitals, or health plans has
      been evaluated as the proportion of total variance (or intraclass correlation,
      ICC) in a quality measure; low ICCs have been interpreted to indicate low
      potential for quality improvement at that level. However, the absolute amount of
      variation, expressed in clinically meaningful units, is less frequently reported.
      Moreover, changes in variance components have not been studied as quality
      improves. OBJECTIVES: To examine changes in variance components at primary care
      physician and medical facility levels as performance improved for 4 quality
      indicators: systolic blood pressure levels in hypertension; low-density
      lipoprotein-cholesterol levels in hyperlipidemia; patient-reported care
      experience scores after primary care visits; and mammography screening rates.
      POPULATION: Adult members (n = 62,596-410,976) of Kaiser Permanente in Northern
      California, served by more than 1000 primary care physicians in 35 facilities,
      from 2001 to 2006. METHODS: Multilevel linear and logistic regression to examine
      the interphysician and interfacility variances in 4 quality indicators over 6
      years, after case-mix adjustment. RESULTS: ICCs were low for all 4 indicators at
      both levels (0.0021-0.086). Nevertheless, variances at both levels were
      statistically and clinically significant. For systolic blood pressure and the
      care experience score, interfacility and interphysician variance as well as ICCs
      decreased further as quality improved; declines were greater at the facility
      level. For low-density lipoprotein-cholesterol, variability at both levels
      increased with quality improvement; and for screening mammography, small declines
      were not statistically significant for either physicians or facilities.
      CONCLUSIONS: Low proportions of variance do not predict low potential for quality
      improvement. Despite low ICCs for facilities, quality improvement efforts
      directed primarily at facilities improved quality for all 4 indicators.

PMID- 20057331
TI  - It's about time: physicians' perceptions of time constraints in primary care
      medical practice in three national healthcare systems.
AB  - BACKGROUND: As physicians are pressured to deliver an increasing number of
      preventive services, follow guidelines, engage in evidence-based practice, and
      deliver patient-centered care in managerially driven organizations, they struggle
      with how much control they have over their time. METHODS: A secondary analysis
      was conducted with data from 3 parallel studies of clinical decision making in
      Germany, the United Kingdom, and the United States with 128 physicians per
      country. Physicians reported how much time they were allocated and how much time
      they needed for high-quality care for new patient appointments, routine
      consultations, and complete physicals. They also reported how much control they
      had over their time in the office and spending adequate time with patients.
      RESULTS: German, British, and American physicians were allocated (on average)
      16/11/32 minutes for a new patient appointment, 6/10/18 minutes for a routine
      visit, and 12/20/36 minutes for a complete physical, but felt that they needed
      more time. Over half of German and American physicians felt that they always or
      usually had control over the hours they were required to be in their office or
      spending sufficient time with their patients while less than half of British
      physicians felt this way. CONCLUSION: German physicians had the least time
      allocated and needed for most types of appointment. American physicians had the
      most time allocated and needed for each type of appointment. However, British
      physicians felt they had the least control over time in their office and spending
      sufficient time with patients.

PMID- 20057332
TI  - Part D plan enrollment by uninsured medicare beneficiaries.
AB  - OBJECTIVES: The objective of the study was to examine the patient factors and
      medication acquisition strategies that impacted PDP enrollment in early 2006 by
      Medicare beneficiaries without prior drug coverage. RESEARCH DESIGN AND SUBJECTS:
      A retrospective cohort study identified 2282 Medicare beneficiaries without prior
      drug coverage from the 2005 Access to Care Module of the Medicare Current
      Beneficiary Survey. MEASURES: Bivariate statistics (eg, chi and t-tests) were
      used to compare beneficiaries without drug coverage in 2005 who enrolled or did
      not enroll in a PDP in early 2006. A logistic regression was estimated to examine
      which patient factors were associated with PDP enrollment, controlling for
      demographic, socioeconomic, and health status variables, as well as medication
      purchasing strategies and size of the PDP choice set. RESULTS: In early 2006, 44%
      of Medicare beneficiaries without prior drug coverage enrolled in a standalone
      PDP. Beneficiaries without prior drug coverage were more likely to enroll if they
      were younger (age 65-74), female, non-Hispanic white, married or widowed, had
      more self-reported conditions, requested prescription drug samples from their
      provider, or compared medication prices prior to purchase. Seniors without prior
      drug coverage were less likely to enroll if they had incomes <$50,000 or obtained
      medication via mail or the internet. CONCLUSIONS: Enrollment in PDPs by
      beneficiaries without prior drug coverage was fairly low in early 2006, and
      vulnerable subgroups of these beneficiaries who did not enroll require follow-up
      to ensure that they realized the benefits of the Medicare Part D program.

PMID- 20057333
TI  - Hospital stroke volume and case-fatality revisited.
AB  - BACKGROUND: A few studies have found an inverse association between hospital
      patient volume and case-fatality among stroke patients. However, the different
      stroke categorizations used in these studies might have influenced the findings.
      Furthermore, the relevance of the association observed remains questionable given
      that the relatively small magnitude may not support volume-based referral
      policies. We re-examined this association in a large nationwide study, paying
      attention to the influence of volume categorizations. METHODS: Applying
      multilevel logistic regression, we re-examined the relationship between hospital
      stroke volume and 7-day case-fatality using admissions data obtained from
      Statistics Netherlands on 73,077 stroke patients for the years 2000 to 2004.
      Different cut-offs were used to categorize hospitals in volume groups. We also
      examined the implications of a volume based referral strategy. RESULTS: Stroke
      patients in high-volume hospitals had decreased risk of dying within 7 days of
      admission even when different hospital categorizations are applied. For instance,
      the odds ratio was 0.45(95% CI 0.20-0.99) in high-volume(>200 case-volume) versus
      low-volume(<50 case-volume) hospitals, but 0.89(95% CI 0.79-1.00) in high
      volume(>250 case-volume) versus low-volume (< or =250 case-volume) hospitals.
      Ignoring travel time and workload implications an optimistic volume-based
      referral policy would save 183 patients when all patients are referred to the
      >200 case-volume hospital. A nontransfer policy aimed at reducing mortality by
      10% in all those hospitals would save 1260 patients. CONCLUSION: Stroke patients
      in low-volume versus high-volume hospitals have higher odds of dying. This
      finding may not lend itself to a substantial volume-based referral strategy.

PMID- 20057334
TI  - Meaningful variation in performance: a systematic literature review.
AB  - BACKGROUND: Recommendations for directing quality improvement initiatives at
      particular levels (eg, patients, physicians, provider groups) have been made on
      the basis of empirical components of variance analyses of performance. OBJECTIVE:
      To review the literature on use of multilevel analyses of variability in quality.
      RESEARCH DESIGN: Systematic literature review of English-language articles (n =
      39) examining variability and reliability of performance measures in Medline
      using PubMed (1949-November 2008). RESULTS: Variation was most commonly assessed
      at facility (eg, hospital, medical center) (n = 19) and physician (n = 18)
      levels; most articles reported variability as the proportion of total variation
      attributable to given levels (n = 22). Proportions of variability explained by
      aggregated levels were generally low (eg, <19% for physicians), and numerous
      authors concluded that the proportion of variability at a specific level did not
      justify targeting quality interventions to that level. Few articles based their
      recommendations on absolute differences among physicians, hospitals, or other
      levels. Seven of 12 articles that assessed reliability found that reliability was
      poor at the physician or hospital level due to low proportional variability and
      small sample sizes per unit, and cautioned that public reporting or incentives
      based on these measures may be inappropriate. CONCLUSIONS: The proportion of
      variability at levels higher than patients is often found to be "low." Although
      low proportional variability may lead to poor measurement reliability, a number
      of authors further suggested that it also indicates a lack of potential for
      quality improvement. Few studies provided additional information to help
      determine whether variation was, nevertheless, clinically meaningful.

PMID- 20057335
TI  - Modulation of Lgl1 by steroid, retinoic acid, and vitamin D models complex
      transcriptional regulation during alveolarization.
AB  - Alveolarization depends on circulating glucocorticoid (GC), retinoid (RA), and
      vitamin D (VitD). Bronchopulmonary dysplasia, a leading cause of neonatal
      morbidity, is associated with arrested alveolarization. In hyperoxia-exposed rats
      displaying features of bronchopulmonary dysplasia, reduced levels of late
      gestation lung 1 (Lgl1) normalize during recovery. We show that GC (100 nM)
      stimulates (7- to 115-fold) and VitD (100 microM) suppresses (twofold) Lgl1
      expression. RA (all-trans/9-cis, 10 microM) effects are biphasic. From postnatal
      days 7-10, RA was stimulatory (twofold) at 24 h, after which effects were
      inhibitory (3- to 15-fold). Lgl1 promoter-luciferase reporter assays confirmed
      that these agents operated at the transcriptional level. Interestingly, the
      individual inhibitory effects of VitD and RA on GC induction of Lgl1 were
      abrogated when both agents were present, suggesting that steric hindrance may
      influence promoter accessibility. Analysis of the proximity (<50 base pairs) of
      binding sites for overlapping VitD and RA receptors to that of the GC receptor
      identified 81% of promoters in 66 genes (including Lgl1) important in human lung
      development compared with 48% in a random set of 1000 genes. Complex integration
      of the effects of GC, RA, and VitD on gene expression in the postnatal lung is
      likely to contribute to the timely advance of alveolarization without attendant
      inflammation.

PMID- 20057336
TI  - A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for
      neonatal jaundice in the Malay population.
AB  - The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene
      encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the
      contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the
      genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal
      jaundice (patients) and in infants without neonatal jaundice (controls). In our
      population study, only c.-3279T>G was associated with neonatal jaundice. The
      genotype distributions between both groups were significantly different (p =
      0.003): the frequency of homozygosity for c.-3279G was much higher in patients
      than those in controls. Allele frequency of c.-3279G was significantly higher in
      patients than those in controls (p = 0.006). We then investigated changes in
      transcriptional activity because of c.-3279T>G. Luciferase reporter assay in
      HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was
      significantly lower than that of the c.-3279T allele in both the absence and
      presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that
      c.-3279T>G modified the synergistic effects of the nuclear factors associated
      with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the
      UGT1A1 promoter is a genetic risk factor for neonatal jaundice.

PMID- 20057337
TI  - Glutathione synthesis rates in early postnatal life.
AB  - Preterm infants have diminished antioxidant defenses. Glutathione (GSH), the main
      intracellular antioxidant, increases upon amino acid (AA) administration in
      preterm infants, without an accompanying rise of the fractional synthesis rate of
      GSH (FSRGSH) This study investigated the mechanism behind this increased GSH
      concentration by determining GSH synthesis in the first days after birth using
      stable isotope techniques in very low-birth-weight (VLBW) infants receiving i.v.
      AAs. Advanced oxidized protein products (AOPPs) were determined to quantify
      oxidative stress. Eighteen infants (birth weight 989 +/- 241 g, gestational age
      of 27/7 +/- 1/7 weeks) were studied either on postnatal day 1 or 2 (7 or 31 h
      postnatally, respectively). Concentration of GSH increased with postnatal age
      (1.45 +/- 0.48 mM versus 1.99 +/- 0.40 mM, p = 0.019). FSRGSH was not
      significantly different, but the absolute synthesis rate of GSH (ASRGSH) tended
      to be higher in the infants studied on day 2 [8.1 +/- 2.7 mg/(kg . d) versus 10.6
      +/- 2.4 mg/(kg . d), p = 0.054]. AOPP concentrations were not different between
      groups. In conclusion, GSH concentration in VLBW infants increases significantly
      after birth. A concomitant increased synthesis rate was not found, suggesting
      that GSH consumption decreases upon AA administration.

PMID- 20057338
TI  - Dynamic ultrasound study on urinary bladder in infants with antenatally detected
      fetal hydronephrosis.
AB  - To evaluate bladder function in infants with antenatally diagnosed hydronephrosis
      (ANH) using dynamic ultrasound protocol. Forty consecutive male infants (mean,
      0.25 y) with ANH and 33 age-matched normal controls (mean, 0.49 y) were
      recruited. Anteroposterior (AP) diameter of renal pelvis (RP) and hydronephrosis
      index [HI = anteroposterior diameter of RP of kidney divided by urinary bladder
      volume (BV)] were calculated. Maximum BV (MaxBV) was determined just before
      voiding. Residual volume (RV) and bladder wall thickness (BWT) were measured
      after spontaneous voiding. Thirty-one infants (77.5%) showed persistently dilated
      RP postnatally in which 12 (39%) showed significantly high HI. In general, ANH
      infants had smaller MaxBV (30.71 versus 52.45 mL), larger residual volume (2.47
      versus 1.93 mL), and larger BWT (4.4 versus 3.7 mm) than normal (p < 0.05, Mann
      Whitney test). Infants with abnormally high HI had significantly more disturbed
      bladder parameters [smaller MaxBV (23.33 versus 33.49 mL) and larger BWT (4.67
      versus 3.79 mm)] than the normal HI group (p < 0.05, Mann-Whitney test). Abnormal
      functional bladder parameters were evident in ANH infants. We postulated that
      immature function in the pelviureteric junction was associated with bladder
      dysfunction in these infants. Dynamic ultrasound protocol might help to
      understand the underlying pathophysiology of urinary system in ANH infants.
      ABBREVIATIONS: :

PMID- 20057340
TI  - IGF2 gene variants and risk of hypertension in obese children and adolescents.
AB  - Obese children have a great risk of hypertension and cardiovascular morbidity in
      adults. The insulin-like growth factor type II (IGF-II) regulates glucose
      homeostasis, cardiovascular functions, and lipid metabolism. IGF2 gene variants
      have shown a strong association with weight, body mass index (BMI), and metabolic
      profile in adults. We performed the molecular screening of two IGF2 polymorphisms
      (6815 A/T, 820 G/A), in 227 obese children to evaluate the potential association
      between IGF2 variants with either obesity or high blood pressure (assessed with a
      24-h holter system) or both. A second cohort of age-, sex-, and BMI-matched
      children were enrolled to confirm any eventual association. We observed a
      significant association between the 6815 A/T IGF2 gene variant and high systolic
      blood pressure in obese children. Homozygote subjects for the T6815 allele
      showed, even in 24-h measurements, a higher risk to develop hypertension than
      those carrying the A6815 allele (OR = 3.7, 95% CI: 1.59-8.66). This result was
      confirmed in the second cohort (OR = 4.1, 95% CI: 1.41-6.50). Any statistically
      significant difference in terms of BMI between the genotype groups was observed.
      Our results suggest that IGF2 gene variants are involved in the blood pressure
      regulation in obese children.

PMID- 20057341
TI  - Neurological condition of infants born after in vitro fertilization with
      preimplantation genetic screening.
AB  - Aim of this study was to evaluate the effect of preimplantation genetic screening
      (PGS) on neurodevelopmental outcome in children. We conducted a prospective
      follow-up study of children born to women randomly assigned to in vitro
      fertilization with or without PGS. Primary outcome was adverse neurologic outcome
      at 18 mo; secondary outcomes were types of minor neurologic dysfunction (MND),
      neurologic outcome before 18 mo, neonatal intensive care admission, and
      congenital malformations. Twenty women in the PGS group participated with 25
      children and 26 women in the control group participated with 31 children. Five
      PGS pregnancies (25%) and four control pregnancies (15%) resulted in birth of at
      least one child with an adverse neurologic outcome (adjusted odds ratio: 2.3 [0.4
      12.0]). Dysfunction in fine motor abilities and posture and muscle tone
      dysregulation tended to be present more frequently after PGS. Neurologic outcome
      before 18 mo, neonatal intensive care admission, and prevalence of congenital
      malformations were similar in study and control pregnancies. Nevertheless, at
      child level, rates of adverse outcome were higher after PGS. In conclusion,
      outcome in pregnancies after in vitro fertilization (IVF) with and without PGS
      was similar. The small sample size precludes the conclusion that PGS is not
      associated with less favorable neurologic outcome. Safety of new assisted
      reproductive techniques should be evaluated before large-scale implementation.
      ABBREVIATIONS: :

PMID- 20057342
TI  - Long-term follow-up of acute retinal necrosis.
AB  - PURPOSE: The purpose of this study was to report long-term visual outcome of
      acute retinal necrosis. METHODS: Medical records of patients with acute retinal
      necrosis were reviewed. RESULTS: Thirty-two patients were diagnosed with acute
      retinal necrosis from 1998 to 2007. Twenty patients (25 eyes) had at least 1
      follow-up and available medical records. Intravitreal injections of ganciclovir
      and/or foscarnet were administered in 11 of 25 eyes. Intravenous and oral
      antiviral medications were used in 14 of 20 and 19 of 20 patients, respectively.
      Eleven of 25 eyes had <25% of retina affected, 8 of 25 had 25% to 50% of retina
      affected, and 6 of 25 had >50% of retina affected. Mean visual acuity at all time
      points was best when retinitis involved <25% and decreased as area increased. All
      but 1 eye with >50% involvement experienced decreased vision regardless of
      treatment. Three of 4 eyes with 25% to 50% involvement that received intravitreal
      antivirals had an improvement in visual acuity of > or =2 Snellen lines. Five of
      25 eyes developed retinal detachment. None of the six eyes treated with
      prophylactic laser detached. CONCLUSION: Greater extent of retinitis portends a
      worse visual prognosis. Although intravitreal treatment did not prevent visual
      acuity loss in patients with severe disease, patients with moderate disease (25
      50% retina involved) did well with intravitreal therapy with most having stable
      or improved visual acuity. Prophylactic laser decreased the rate of detachment.

PMID- 20057343
TI  - Novel and homozygous BEST1 mutations in Chinese patients with Best vitelliform
      macular dystrophy.
AB  - PURPOSE: The purpose of this study was to investigate the BEST1 gene mutations in
      Chinese patients with Best vitelliform macular dystrophy (BVMD). METHODS: Twenty
      six subjects from 7 Chinese families with BVMD and 100 unrelated healthy Chinese
      subjects without a family history of BVMD were screened for mutations in the
      BEST1 gene by direct sequencing. The subjects underwent complete ophthalmologic
      examination and BEST1 gene screening. RESULTS: Six novel missense mutations
      (Thr2Asn, Leu75Phe, Ser144Asn, Arg255Trp, Pro297Thr, and Asp301Gly) and 1
      previously reported mutation (Arg218Cys) were identified. Each family was found
      to have a unique BEST1 mutation that segregated with the disease. Two of the six
      novel mutations are located within the four previously reported common mutation
      clusters within the BEST1 gene. One family with patients having homozygous
      Leu75Phe mutations did not have the more severe BVMD phenotype. None of the
      patients with mutations was identified among the 100 healthy control subjects.
      CONCLUSION: A large number of unique novel missense mutations was found in
      Chinese patients with BVMD, suggesting considerable interethnic differences
      between the mutation sites in the BEST1 gene in different populations. The few
      truncating BEST1 mutations and the lack of a more severe phenotype in homozygous
      patients suggest that the missense BEST1 mutation may produce a dominant negative
      effect on wild-type BEST1 gene.

PMID- 20057344
TI  - Intravitreal triamcinolone as an adjunct to standard laser therapy in coexisting
      high-risk proliferative diabetic retinopathy and clinically significant macular
      edema.
AB  - PURPOSE: To evaluate the efficacy and safety of combined intravitreal
      triamcinolone acetonide (IVTA) injection plus panretinal photocoagulation (PRP)
      and macular photocoagulation (MPC) in comparison with PRP and MPC in eyes with
      coexisting high-risk proliferative diabetic retinopathy (PDR) and clinically
      significant macular edema (CSME). METHODS: Twenty-three patients diagnosed with
      both high-risk PDR and CSME were enrolled in our prospective, randomized clinical
      trial study. One eye of each patient was selected to undergo IVTA injection one
      week before initial PRP and MPC (IVTA eye), and the other eye was treated with
      PRP and MPC (control eye) based on block randomization. Panretinal
      photocoagulation was performed in 3 sessions at 1 week intervals. Baseline
      characteristics included best-corrected visual acuity (BCVA) using Snellen
      charts, intraocular pressure and patients were observed at 1, 4, and 6 months of
      treatment. Main outcome measures included change in central macular thickness
      (CMT) as measured by optical coherence tomography (OCT), logarithm of the minimum
      angle of resolution BCVA (logMAR), and complications occurring within the follow
      up period. RESULTS: Of 23 enrolled patients, 5 patients did not complete follow
      up visits due to dense vitreous hemorrhage, tractional retinal detachment and
      loss of future follow-up. Mean baseline logMAR BCVA was 0.46 +/- 0.29 and 0.56 +/
      0.27 in IVTA eyes and controls. Final mean logMAR BCVA was 0.39 +/- 0.29 (IVTA
      eyes) and 0.55 +/- 0.33 (control eyes), which was not significantly different (P
      = 0.08). Mean baseline CMT was 319.2 +/- 79.1 microm (IVTA eyes) and 345.9 +/-
      100.6 microm (control eyes). Significant reduction of CMT in IVTA eyes was
      observed at 1 month (P = 0.024), which had not remained stable after 6 months
      showing no significant difference as compared with baseline CMT (P = 0.06). In
      control eyes, CMT was not significantly reduced at 1 and 6 months of treatment.
      The standardized change in macular thickening (SCMT) was 29.4 +/- 52.2 (IVTA
      group) versus 5.66 +/- 31.5 (control group) (P = 0.12) at 1 month. At 6 months,
      SCMT was 16.8 +/- 55.8 (IVTA group) versus 5.03 +/- 47.4 (control group) (P =
      0.51). CONCLUSION: Combined IVTA plus PRP and MPC in coexisting high-risk PDR and
      CSME eyes do not have a significant beneficial effect on BCVA improvement and CMT
      reduction compared with standard treatment.

PMID- 20057349
TI  - Multistate outbreak of human Salmonella typhimurium infections associated with
      aquatic frogs - United States, 2009.
AB  - During April-July 2009, the Utah Department of Health identified five cases of
      Salmonella Typhimurium infection with indistinguishable pulsed-field gel
      electrophoresis (PFGE) patterns, predominantly among children. In August, CDC
      began a multistate outbreak investigation to determine the source of the
      infections. This report summarizes the results of this ongoing investigation,
      which, as of December 30, had identified 85 S. Typhimurium human isolates with
      the outbreak strain from 31 states. In a multistate case-control study, exposure
      to frogs was found to be significantly associated with illness (63% of cases
      versus 3% of controls; matched odds ratio [mOR] = 24.4). Among 14 case-patients
      who knew the type of frog, all had exposure to an exclusively aquatic frog
      species, the African dwarf frog. Environmental samples from aquariums containing
      aquatic frogs in four homes of case-patients yielded S. Typhimurium isolates
      matching the outbreak strain. Preliminary traceback information has indicated
      these frogs likely came from the same breeder in California. Reptiles (e.g.,
      turtles) and amphibians (e.g., frogs) have long been recognized as Salmonella
      carriers, and three multistate outbreaks of human Salmonella infections
      associated with turtle contact have occurred since 2006. However, this is the
      first reported multistate outbreak of Salmonella infections associated with
      amphibians. Educational materials aimed at preventing salmonellosis from contact
      with reptiles should be expanded to include amphibians, such as aquatic frogs.

PMID- 20057350
TI  - Patients hospitalized with 2009 pandemic influenza A (H1N1) - New York City, May
      2009.
AB  - The first cases of 2009 pandemic influenza A (H1N1) in New York City occurred in
      April 2009, raising many questions about how best to contain the epidemic. To
      rapidly assess the severity of influenza illness and identify persons at highest
      risk for severe infection, the New York City (NYC) Department of Health and
      Mental Hygiene (DOHMH) reviewed the medical charts of the first 99 patients with
      laboratory confirmed H1N1 admitted to any NYC hospital. The purpose of the review
      was to characterize the demographics of the first hospitalized patients, identify
      associated underlying medical conditions, describe the course and severity of
      disease, and examine the use of antiviral medications. This report summarizes the
      findings of this analysis. Approximately 60% of admitted patients were aged <;18
      years. The most commonly documented underlying condition was asthma, observed
      among 50% of patients aged <18 years and 46% of adult patients. Multiple
      underlying conditions were observed in 17% of patients (12% of children, 24% of
      adults). Patients treated with oseltamivir within 2 days of symptom onset had
      shorter median hospitalizations than those who did not (2 days versus 3 days [p =
      0.03]). The findings of this assessment were used to inform immediate outbreak
      response measures in New York City. During such outbreaks, public education
      campaigns should encourage patients at high risk of severe illness to seek
      treatment promptly after symptom onset and should emphasize the importance of
      early antiviral therapy for patients with underlying risk conditions.

PMID- 20057351
TI  - Outbreak of 2009 pandemic influenza A (H1N1) at a school - Hawaii, May 2009.
AB  - The first cases of 2009 H1N1 pandemic influenza were reported by CDC on April 21,
      2009. Twenty-one days later, on May 12, the Hawaii Department of Health (HDOH)
      confirmed two pandemic H1N1 cases from the same school in Oahu. One case was in
      an 8th-grade student and the other in a 3rd-grade teacher. HDOH initiated an
      investigation to determine the extent of transmission at the school and among
      household contacts, and to help establish appropriate control strategies. This
      report summarizes the results of the investigation, which detected an outbreak of
      pandemic H1N1 cases at the school over the ensuing 3 weeks. A total of 16 cases
      were identified; all patients recovered with no hospitalizations or deaths. HDOH,
      the school, and the Hawaii Department of Education (HDOE) instituted an education
      campaign asking students and employees to stay home if ill. After consulting with
      HDOH, school officials decided not to close the school; the outbreak ended after
      19 days. This outbreak represented the first documented community transmission of
      pandemic H1N1 virus in Hawaii. The investigation contributed to the early
      understanding of the epidemiology of H1N1 influenza in Hawaii (e.g., that risk
      factors for infection would not be restricted to mainland or foreign travel) and
      the likely role that endemic transmission would play. Influenza activity in
      schools can serve to inform local public health officials of changing disease
      patterns, especially early in an epidemic.

PMID- 20057352
TI  - Using the gene pulser MXcell electroporation system to transfect primary cells
      with high efficiency.
AB  - It is becoming increasingly apparent that electroporation is the most effective
      way to introduce plasmid DNA or siRNA into primary cells. The Gene Pulser MXcell
      electroporation system and Gene Pulser electroporation buffer (Bio-Rad) were
      specifically developed to easily transfect nucleic acids into mammalian cells and
      difficult-to-transfect cells, such as primary and stem cells. We will demonstrate
      how to perform a simple experiment to quickly identify the best electroporation
      conditions. We will demonstrate how to run several samples through a range of
      electroporation conditions so that an experiment can be conducted at the same
      time as optimization is performed. We will also show how optimal conditions
      identified using 96-well electroporation plates can be used with standard
      electroporation cuvettes, facilitating the switch from electroporation plates to
      electroporation cuvettes while maintaining the same electroporation efficiency.
      In the video, we will also discuss some of the key factors that can lead to the
      success or failure of electroporation experiments.

PMID- 20057353
TI  - HipHop interacts with HOAP and HP1 to protect Drosophila telomeres in a sequence
      independent manner.
AB  - Telomeres prevent chromosome ends from being repaired as double-strand breaks
      (DSBs). Telomere identity in Drosophila is determined epigenetically with no
      sequence either necessary or sufficient. To better understand this sequence
      independent capping mechanism, we isolated proteins that interact with the
      HP1/ORC-associated protein (HOAP) capping protein, and identified HipHop as a
      subunit of the complex. Loss of one protein destabilizes the other and renders
      telomeres susceptible to fusion. Both HipHop and HOAP are enriched at telomeres,
      where they also interact with the conserved HP1 protein. We developed a model
      telomere lacking repetitive sequences to study the distribution of HipHop, HOAP
      and HP1 using chromatin immunoprecipitation (ChIP). We discovered that they
      occupy a broad region >10 kb from the chromosome end and their binding is
      independent of the underlying DNA sequence. HipHop and HOAP are both rapidly
      evolving proteins yet their telomeric deposition is under the control of the
      conserved ATM and Mre11-Rad50-Nbs (MRN) proteins that modulate DNA structures at
      telomeres and at DSBs. Our characterization of HipHop and HOAP reveals functional
      analogies between the Drosophila proteins and subunits of the yeast and mammalian
      capping complexes, implicating conservation in epigenetic capping mechanisms.

PMID- 20057354
TI  - Positional dependence of transcriptional inhibition by DNA torsional stress in
      yeast chromosomes.
AB  - How DNA helical tension is constrained along the linear chromosomes of eukaryotic
      cells is poorly understood. In this study, we induced the accumulation of DNA (+)
      helical tension in Saccharomyces cerevisiae cells and examined how DNA
      transcription was affected along yeast chromosomes. The results revealed that,
      whereas the overwinding of DNA produced a general impairment of transcription
      initiation, genes situated at <100 kb from the chromosomal ends gradually escaped
      from the transcription stall. This novel positional effect seemed to be a simple
      function of the gene distance to the telomere: It occurred evenly in all 32
      chromosome extremities and was independent of the atypical structure and
      transcription activity of subtelomeric chromatin. These results suggest that DNA
      helical tension dissipates at chromosomal ends and, therefore, provides a
      functional indication that yeast chromosome extremities are topologically open.
      The gradual escape from the transcription stall along the chromosomal flanks also
      indicates that friction restrictions to DNA twist diffusion, rather than tight
      topological boundaries, might suffice to confine DNA helical tension along
      eukaryotic chromatin.

PMID- 20057355
TI  - ATR activation and replication fork restart are defective in FANCM-deficient
      cells.
AB  - Fanconi anaemia is a chromosomal instability disorder associated with cancer
      predisposition and bone marrow failure. Among the 13 identified FA gene products
      only one, the DNA translocase FANCM, has homologues in lower organisms,
      suggesting a conserved function in DNA metabolism. However, a precise role for
      FANCM in DNA repair remains elusive. Here, we show a novel function for FANCM
      that is distinct from its role in the FA pathway: promoting replication fork
      restart and simultaneously limiting the accumulation of RPA-ssDNA. We show that
      in DT40 cells this process is controlled by ATR and PLK1, and that in the absence
      of FANCM, stalled replication forks are unable to resume DNA synthesis and genome
      duplication is ensured by excess origin firing. Unexpectedly, we also uncover an
      early role for FANCM in ATR-mediated checkpoint signalling by promoting chromatin
      retention of TopBP1. Failure to retain TopBP1 on chromatin impacts on the ability
      of ATR to phosphorylate downstream molecular targets, including Chk1 and SMC1.
      Our data therefore indicate a fundamental role for FANCM in the maintenance of
      genome integrity during S phase.

PMID- 20057356
TI  - Identification of a novel Bves function: regulation of vesicular transport.
AB  - Blood vessel/epicardial substance (Bves) is a transmembrane protein that
      influences cell adhesion and motility through unknown mechanisms. We have
      discovered that Bves directly interacts with VAMP3, a SNARE protein that
      facilitates vesicular transport and specifically recycles transferrin and beta-1
      integrin. Two independent assays document that cells expressing a mutated form of
      Bves are severely impaired in the recycling of these molecules, a phenotype
      consistent with disruption of VAMP3 function. Using Morpholino knockdown in
      Xenopus laevis, we demonstrate that elimination of Bves function specifically
      inhibits transferrin receptor recycling, and results in gastrulation defects
      previously reported with impaired integrin-dependent cell movements. Kymographic
      analysis of Bves-depleted primary and cultured cells reveals severe impairment of
      cell spreading and adhesion on fibronectin, indicative of disruption of integrin
      mediated adhesion. Taken together, these data demonstrate that Bves interacts
      with VAMP3 and facilitates receptor recycling both in vitro and during early
      development. Thus, this study establishes a newly identified role for Bves in
      vesicular transport and reveals a novel, broadly applied mechanism governing
      SNARE protein function.

PMID- 20057357
TI  - GPI anchoring facilitates propagation and spread of misfolded Sup35 aggregates in
      mammalian cells.
AB  - Prion diseases differ from other amyloid-associated protein misfolding diseases
      (e.g. Alzheimer's) because they are naturally transmitted between individuals and
      involve spread of protein aggregation between tissues. Factors underlying these
      features of prion diseases are poorly understood. Of all protein misfolding
      disorders, only prion diseases involve the misfolding of a
      glycosylphosphatidylinositol (GPI)-anchored protein. To test whether GPI
      anchoring can modulate the propagation and spread of protein aggregates, a GPI
      anchored version of the amyloidogenic yeast protein Sup35NM (Sup35GPI) was
      expressed in neuronal cells. Treatment of cells with Sup35NM fibrils induced the
      GPI anchor-dependent formation of self-propagating, detergent-insoluble, protease
      resistant, prion-like aggregates of Sup35GPI. Live-cell imaging showed
      intercellular spread of Sup35GPI aggregation to involve contact between aggregate
      positive and aggregate-negative cells and transfer of Sup35GPI from aggregate
      positive cells. These data demonstrate GPI anchoring facilitates the propagation
      and spread of protein aggregation and thus may enhance the transmissibility and
      pathogenesis of prion diseases relative to other protein misfolding diseases.

PMID- 20057358
TI  - SLR-2 and JMJC-1 regulate an evolutionarily conserved stress-response network.
AB  - Maintaining a homeostatic interaction with the environment is crucial for the
      growth, survival, and propagation of all living organisms. Reestablishment of
      equilibrium after stress is achieved by the activation of complex transcriptional
      response networks, many of which remain poorly understood. Here, we report that
      the zinc-finger protein, SLR-2, is a master stress regulator and is required for
      the normal response to pleiotropic stress conditions in Caenorhabditis elegans.
      Using bioinformatical tools, we identified an evolutionarily conserved nucleotide
      motif present in slr-2 stress-responsive genes and show that this motif is
      sufficient for stress induction under a variety of conditions. We also
      demonstrate that JMJC-1, a conserved Jumonji C domain protein, acts downstream of
      SLR-2 to mediate stress response in C. elegans. Moreover, the role of JMJC-1 in
      stress response is conserved in Drosophila and mammals. Finally, we provide
      evidence that the SLR-2-JMJC-1 pathway functions independently of the well
      studied DAF-16/FOXO1 network. These findings point to a previously unrecognized
      phylogenetically conserved master stress-response pathway in metazoa.

PMID- 20057359
TI  - Postexercise hypotension in an endurance-trained population of men and women
      following high-intensity interval and steady-state cycling.
AB  - BACKGROUND: The acute effect of high-intensity interval exercise (HI) on blood
      pressure (BP) is unknown although this type of exercise has similar or greater
      cardiovascular benefits compared to steady-state aerobic exercise (SS). This
      study examined postexercise hypotension (PEH) and potential mechanisms of this
      response in endurance-trained subjects following acute SS and HI. Sex differences
      were also evaluated. METHODS: A total of 25 endurance-trained men (n = 15) and
      women (n = 10) performed a bout of HI and a bout of SS cycling in randomized
      order on separate days. Before exercise, 30 min postexercise, and 60 min
      postexercise, we measured brachial and aortic BP. Cardiac output (CO), stroke
      volume (SV), end diastolic volume (EDV), end systolic volume (ESV), and left
      ventricular wall-velocities were measured using ultrasonography with tissue
      Doppler capabilities. Ejection fraction and fractional shortening (FS), total
      peripheral resistance (TPR), and calf vascular resistance were calculated from
      the above variables and measures of leg blood flow. RESULTS: BP, ejection
      fraction, and FS decreased by a similar magnitude following both bouts but
      changes in CO, heart rate (HR), TPR, and calf vascular resistance were greater in
      magnitude following HI than following SS. Men and women responded similarly to
      HI. Although men and women exhibited a similar PEH following SS, they showed
      differential changes in SV, EDV, and TPR. CONCLUSIONS: HI acutely reduces BP
      similarly to SS. The mechanistic response to HI appears to differ from that of
      SS, and endurance-trained men and women may exhibit differential mechanisms for
      PEH following SS but not HI.

PMID- 20057360
TI  - Adipose tissue-specific regulation of angiotensinogen in obese humans and mice:
      impact of nutritional status and adipocyte hypertrophy.
AB  - BACKGROUND: The adipose tissue renin-angiotensin system (RAS) has been implicated
      in the pathophysiology of obesity and dysfunction of adipose tissue. However,
      neither regulation of angiotensinogen (AGT) expression in adipose tissue nor
      secretion of adipose tissue-derived AGT has been fully elucidated in humans.
      METHODS: Human subcutaneous abdominal adipose tissue (SAT) biopsies were
      performed for 46 subjects with a wide range of body mass index (BMI). Considering
      the mRNA level of AGT and indices of body fat mass, the amount of adipose tissue
      derived AGT secretion (A-AGT-S) was estimated. Using a mouse model of obesity and
      weight reduction, plasma AGT levels were measured with a newly developed enzyme
      linked immunosorbent assay (ELISA), and the contribution of A-AGT-S to plasma AGT
      levels was assessed. RESULTS: A-AGT-S was substantially increased in obese humans
      and the value was correlated with the plasma AGT level in mice. A-AGT-S and
      plasma AGT were higher in obese mice, whereas lower in mice with weight
      reduction. However, the AGT mRNA levels in the liver, kidney, and aorta were not
      altered in the mouse models. In both humans and mice, the AGT mRNA levels in
      mature adipocytes (MAs) were comparable to those in stromal-vascular cells.
      Coulter Multisizer analyses revealed that AGT mRNA levels in the MAs were
      inversely correlated with the average size of mature adipocytes. CONCLUSIONS:
      This study demonstrates that adipose tissue-derived AGT is substantially
      augmented in obese humans, which may contribute considerably to elevated levels
      of circulating AGT. Adipose tissue-specific regulation of AGT provides a novel
      insight into the clinical implications of adipose tissue RAS in human obesity.

PMID- 20057361
TI  - Impaired flow-mediated vasodilatation is associated with increased left
      ventricular mass in a multiethnic population. The Northern Manhattan Study.
AB  - BACKGROUND: Increased left ventricular (LV) mass and endothelial dysfunction are
      important risk factors for cardiovascular mortality and morbidity. However, it is
      not clear whether endothelial dysfunction is associated with increased LV mass.
      We tested the hypothesis that impaired flow-mediated vasodilatation (FMD) is
      associated with increased LV mass in a population-based multiethnic cohort.
      METHODS: As a part of the Northern Manhattan Study (NOMAS), we performed two
      dimensional echocardiography and FMD assessment during reactive hyperemia by high
      resolution ultrasonography in 867 stroke-free community participants. LV mass was
      calculated according to an established method. LV hypertrophy was defined as the
      90th percentile of sex-specific LV mass indexed for body surface area among
      normal subjects. Multivariable models were used to test the association of FMD
      with LV mass. RESULTS: In multiple linear regression analysis adjusting for age,
      sex, body mass index, systolic blood pressure, antihypertensive medications, low
      density lipoprotein cholesterol, diabetes, smoking, hematocrit, and race
      ethnicity, FMD was inversely associated with LV mass (beta = -1.21 +/- 0.56, P =
      0.03). The association persisted after further adjustment for any component of
      blood pressure (systolic, mean, and pulse pressure). In univariate logistic
      regression analysis, each 1% decrease in FMD was associated with an 8% higher
      risk of LV hypertrophy (odds ratio 1.08, 95% confidence interval 1.03-1.13 per
      each FMD point P < 0.01). CONCLUSIONS: Impaired FMD is associated with LV mass,
      independent of other factors associated with increased LV mass. Endothelial
      dysfunction might be a potential risk factor for LV hypertrophy.

PMID- 20057362
TI  - Endothelial progenitor cell function, apoptosis, and telomere length in
      overweight/obese humans.
AB  - Excess adiposity is associated with increased cardiovascular morbidity and
      mortality. Endothelial progenitor cells (EPCs) play an important role in vascular
      repair. We tested the hypothesis that increased adiposity is associated with EPC
      dysfunction, characterized by diminished capacity to release angiogenic
      cytokines, increased apoptotic susceptibility, reduced cell migration, and
      shorter telomere length. A total of 67 middle-aged and older adults (42-67 years)
      were studied: 25 normal weight (normal weight; BMI: 18.5-24.9 kg/m(2)) and 42
      overweight/obese (overweight/obese; BMI: 25.0-34.9 kg/m(2)). Cells with
      phenotypic EPC characteristics were isolated from peripheral blood. EPC release
      of vascular endothelial growth factor (VEGF) and granulocyte colony-stimulating
      factor (G-CSF) was determined in the absence and presence of phytohemagglutinin
      (10 microg/ml). Intracellular active caspase-3 and cytochrome c concentrations
      were determined by immunoassay. Migratory activity of EPCs in response to VEGF (2
      ng/ml) and stromal cell-derived factor-1alpha (SDF-1alpha; 10 ng/ml) was
      determined by Boyden chamber. Telomere length was assessed by Southern
      hybridization. Phytohemagglutinin-stimulated release of VEGF (90.6 +/- 7.6 vs.
      127.2 +/- 11.6 pg/ml) and G-CSF (896.1 +/- 77.4 vs. 1,176.3 +/- 126.3 pg/ml) was
      ~25% lower (P < 0.05) in EPCs from overweight/obese vs. normal weight subjects.
      Staurosporine induced a ~30% greater (P < 0.05) increase in active caspase-3 in
      EPCs from overweight/obese (2.8 +/- 0.2 ng/ml) compared with normal weight (2.2
      +/- 0.2) subjects. There were no significant differences in EPC migration to
      either VEGF or SDF-1alpha. Telomere length did not differ between groups. These
      results indicate that increased adiposity adversely affects the ability of EPCs
      to release proangiogenic cytokines and resist apoptosis, potentially compromising
      their reparative potential.

PMID- 20057363
TI  - Limited supermarket availability is not associated with obesity risk among
      participants in the Kansas WIC Program.
AB  - Socioecological theory and a growing body of research suggests that geographic,
      racial, ethnic, and socioeconomic disparities in the prevalence of obesity are
      linked to disparities in the availability of food retail outlets that provide
      healthy food options. We examined the availability of food stores for low-income
      women in Kansas and tested whether food store availability was associated with
      obesity using cross-sectional, geocoded data from women participating in the
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) (n
      = 21,166) in Kansas. The availability and density of food stores within a 1, 3,
      and 5 mile radius of residence was determined, and multivariate logistic
      regression was used to examine the association of food store availability with
      obesity. The availability of convenience, grocery stores, and supermarkets varied
      across the urban-rural continuum, but the majority of WIC recipients lived within
      a 1 mile radius of a small grocery store. WIC participants in micropolitan areas
      had the greatest availability of food stores within a 1 mile radius of residence.
      Availability and density of food stores was not associated with obesity in
      metropolitan and rural areas, but availability and density of any type of food
      store was associated with an increased risk of obesity among WIC recipients in
      micropolitan areas. These results suggest that limited spatial availability of
      grocery stores and supermarkets does not contribute to obesity risk among low
      income WIC recipients in Kansas, and that urban influence moderates the
      contribution of food environments to obesity.

PMID- 20057364
TI  - Superior appetite hormone profile after equivalent weight loss by gastric bypass
      compared to gastric banding.
AB  - The goal of this study was to understand the mechanisms of greater weight loss by
      gastric bypass (GBP) compared to gastric banding (GB) surgery. Obese weight- and
      age-matched subjects were studied before (T0), after a 12 kg weight loss (T1) by
      GBP (n = 11) or GB (n = 9), and at 1 year after surgery (T2). peptide YY(3-36)
      (PYY(3-36)), ghrelin, glucagon-like peptide-1 (GLP-1), leptin, and amylin were
      measured after an oral glucose challenge. At T1, glucose-stimulated GLP-1 and PYY
      levels increased significantly after GBP but not GB. Ghrelin levels did not
      change significantly after either surgery. In spite of equivalent weight loss,
      leptin and amylin decreased after GBP, but not after GB. At T2, weight loss was
      greater after GBP than GB (P = 0.003). GLP-1, PYY, and amylin levels did not
      significantly change from T1 to T2; leptin levels continued to decrease after
      GBP, but not after GB at T2. Surprisingly, ghrelin area under the curve (AUC)
      increased 1 year after GBP (P = 0.03). These data show that, at equivalent weight
      loss, favorable GLP-1 and PYY changes occur after GBP, but not GB, and could
      explain the difference in weight loss at 1 year. Mechanisms other than weight
      loss may explain changes of leptin and amylin after GBP.

PMID- 20057365
TI  - Meta-analysis added power to identify variants in FTO associated with type 2
      diabetes and obesity in the Asian population.
AB  - Several common variants in the intron 1 of FTO (fat mass and associated obesity)
      gene have been reliably associated with BMI and obesity in European populations.
      We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han
      individuals and conducted a meta-analysis of published studies in Asian
      population to investigate whether these variants are associated with type 2
      diabetes (T2D) and obesity in Asian population. In this study, both the minor
      allele A of rs9939609 and the minor allele A of rs805136 were associated with
      increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per
      copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI),
      1.04-1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07-1.40; P = 0.004) after
      adjusting for age, sex, and BMI. Our results also showed association with risk of
      obesity (rs9939609: OR = 1.39 (95% CI 1.04-1.85), P = 0.02; rs8050136: OR = 1.45
      (95% CI 1.09-1.93), P = 0.01) but no association with overweight. These results
      were consistent with the pooled results from our meta-analysis study (for
      diabetes, rs8050136, P = 1.3 x 10(-3); rs9939609, P = 9.8 x 10(-4); for obesity,
      rs8050136, P = 2.2 x 10(-7); rs9939609, P = 9.0 x 10(-9)). Our findings indicate
      that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to
      obesity and T2D in the Asian populations.

PMID- 20057366
TI  - Longitudinal adaptations to very low-carbohydrate weight-reduction diet in obese
      rats: body composition and glucose tolerance.
AB  - Longitudinal effects of a very low-carbohydrate (VLC) and a calorie-matched high
      carbohydrate (HC) weight reduction diet were compared in dietary obese Sprague
      Dawley rats exhibiting impaired glucose tolerance and insulin resistance. Obese
      rats were divided into weight-matched groups: (i) VLC rats consumed an energy
      restricted 5% carbohydrate, 60% fat diet for 8 weeks, (ii) HC rats consumed an
      isocaloric 60% carbohydrate, 15% fat diet, and (iii) HF rats consumed a high-fat
      diet ad libitum. HC and VLC rats showed similar reductions in body fat and
      hepatic lipid at the midpoint of the weight-reduction program, indicating effects
      due to energy deficit. At the end point, however, HC rats showed greater
      reductions in total and percent body fat, hepatic lipid and intramuscular lipid
      than did VLC rats, suggesting that diet composition induced changes in the
      relative efficiencies of the HC and VLC diets over time. HC rats showed marked
      improvement in glucose tolerance at the midpoint and end point, whereas VLC rats
      showed no improvement. Impaired glucose tolerance in VLC rats at the end point
      was due to insulin resistance and an attenuated insulin secretory response.
      Glucose tolerance in energy-restricted rats correlated negatively with hepatic
      and intramuscular lipid levels, but not visceral or total fat mass. These
      findings demonstrate that adaptations to diet composition eventually enabled HC
      rats to lose more body fat than VLC rats even though energy intakes were equal,
      and suggest that the elevated levels of hepatic and intramuscular lipid
      associated with VLC diets might predispose to insulin resistance and impaired
      glucose tolerance despite weight loss.

PMID- 20057367
TI  - Infusion of a lipid emulsion modulates AMPK and related proteins in rat liver,
      muscle, and adipose tissues.
AB  - The primary objective of this study was to investigate the impact of lipid
      oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue.
      Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered
      saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited
      increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with a
      greater association between AMPK and Ca(2+)/calmodulin-dependent protein kinase
      kinase (CaMKK). No differences in muscle protein phosphatase 2C (PP2C) activity,
      LKB1 phosphorylation or AMPK and LKB1 association were observed. Muscle ACCbeta,
      and adiponectin receptor 1 (AdipoR1) mRNA levels and PPARgamma-co-activator
      1alpha (PGC1alpha) protein levels were also increased in LE-treated rats. In
      contrast, AMPK and ACC phosphorylation decreased and PP2C activity increased in
      rat livers exposed to LE. Hepatic mRNA levels of ACCalpha, PPARalpha, AdipoR1,
      AdipoR2, and sterol regulatory element-binding protein-1c (SREBP1c) were also
      reduced after LE infusion. In adipose tissue, there was no significant alteration
      in AMPK or ACC phosphorylation. These results demonstrate that following lipid
      oversupply the AMPK pathway was enhanced in rat skeletal muscle while diminished
      in the liver and was unchanged in adipose tissue. CaMKK in skeletal muscle and
      PP2C in the liver, at least in part, appear to mediate these alterations.
      Alterations in AMPK pathway in the liver induced metabolic defects associated
      with lipid oversupply.

PMID- 20057368
TI  - Evaluation of a comprehensive care clinic model for children with brain tumor and
      risk for hypothalamic obesity.
AB  - The objectives of this study were to evaluate outcomes of a comprehensive care
      clinic (CCC) for children with hypothalamic obesity due to treatment for brain
      tumors by assessing weight parameters; health-related quality of life (HRQoL);
      and perception of health status, disease burden, care satisfaction, and physical
      activity. Thirty-nine patients (16 males) were reviewed. While attending the CCC
      the median %weight gain and percent ideal body weight (%IBW) of patients was
      lower (8.5%/year (range -3 to -14) and -4%/year (141.7-34), respectively) than
      the median %weight gain and %IBW (21.4% (15.8-32.0) and 19.9% (-18.7 to 149.2))
      while treated in standard care. Rate of increase in %BMI slowed (4.5 kg/m(2)
      %/year (-17.8 to 8.4) vs. 8.4 kg/m(2) %/year (-3.1 to 28.1)) in patients
      attending the clinic compared to their before treatment in standard care. There
      was no change in blood pressure, fasting glucose, triglycerides or low-density
      lipoprotein cholesterol, and a significant increase in high-density lipoprotein
      cholesterol (1.09 +/- 0.33 to 1.24 +/- 0.04). After attending the CCC for a year,
      significant increases for child reported total HRQoL (63.7 +/- 18.4-71.3 +/-
      13.3; P < 0.017), physical functioning (65.3 +/- 15.9-69.5 +/- 15.9; P < 0.045)
      and school functioning (61.1 +/- 21.0-71.1 +/- 16.5; P < 0.051) were found.
      Parents reported no significant change in HRQoL over the same period. Parents had
      significantly improved responses in areas of coordination of health care and
      understanding of their child's disease. Patients attending the CCC gained less
      weight while attending the clinic and exhibited improved HRQoL. Parents noticed
      improvements in various areas of their child's medical care.

PMID- 20057369
TI  - miR-519d overexpression is associated with human obesity.
AB  - Obesity is a consequence of imbalance of food intake and energy expenditure that
      results in storage of energy as fat, primarily in adipose tissue. MicroRNAs are
      non-coding RNAs that regulate gene expression in metabolic pathways and they are
      also involved in fat-cell development. The aim of this study was to evaluate
      whether microRNA dysfunction contributes to obesity. We analyzed, by microarray,
      the expression profile of 1,458 microRNAs in subcutaneous adipose tissue (SAT)
      from nondiabetic severely obese (n = 20) and nonobese adults (n = 8). Among 42
      differently expressed microRNAs, we confirmed by reverse-transcription PCR (RT
      PCR) that miR-519d was overexpressed whereas the protein levels of peroxisome
      proliferator-activated receptor-alpha (PPARA) (a predicted miR 519d target) were
      lower, at western analysis, in severely obese vs. nonobese subjects. We also show
      that miR-519d specifically and dose-dependently suppressed translation of the
      PPARA protein, and increased lipid accumulation during preadipocyte
      differentiation. Because PPARA plays a central role in fatty acid homeostasis,
      and in the transcriptional regulation of genes that are necessary for maintenance
      of the redox balance during the oxidative catabolism of fatty acids, we suggest
      that PPARA loss and miR-519d overexpression could be associated with metabolic
      imbalance and subsequent adipocyte hypertrophy in SAT during obesity.

PMID- 20057370
TI  - Effects of heritability, shared environment, and nonshared intrauterine
      conditions on child and adolescent BMI.
AB  - Heritability studies of BMI, based upon twin samples, have identified genetic and
      shared environmental components of BMI, but have been largely silent about the
      nonshared environmental factors. Intrauterine factors have been identified as
      having significant long-term effects on BMI and may be a critical source of
      nonshared environmental influence. Extant studies based on samples of either
      unrelated individuals or twins cannot separate the effects of genetics, shared
      environments, and nonshared intrauterine conditions because the one lacks
      variation in the degree of relatedness and the other has insufficient variation
      in intrauterine conditions. This study improves upon these prior studies by using
      a large, sibling-based sample to examine heritability, shared environmental, and
      nonshared intrauterine influences on BMI during two age periods in childhood (6-8
      years; 12-14 years). The primary interest was in determining the effects of the
      intrauterine environment on BMI as a component of the nonshared environment and
      in determining whether there were sex-specific differences in heritability and/or
      in the intrauterine factors. These were estimated using regression-based
      techniques introduced by DeFries and Fulker. Heritability of BMI was estimated to
      be 0.20-0.28 at 6-8 years and 0.46-0.61 at 12-14 years. Differences in
      heritability were found at 12-14 years between same-sex as compared to mixed-sex
      pairs. The shared environmental effect was significant at 6-8 years but
      insignificant at 12-14 years. Differences in birth weight were significant in all
      groups at 6-8 years suggesting long-term effects of the nonshared intrauterine
      environment; at 12-14 years, birth weight was no longer significant for girls.

PMID- 20057371
TI  - Long-term successful weight loss improves vascular endothelial function in
      severely obese individuals.
AB  - Obesity is associated with increased cardiovascular risk. Although short-term
      weight loss improves vascular endothelial function, longer term outcomes have not
      been widely investigated. We examined brachial artery endothelium-dependent
      vasodilation and metabolic parameters in 29 severely obese subjects who lost > or
      =10% body weight (age 45 +/- 13 years; BMI 48 +/- 9 kg/m(2)) at baseline and
      after 12 months of dietary and/or surgical intervention. We compared these
      parameters to 14 obese individuals (age 49 +/- 11 years; BMI 39 +/- 7 kg/m(2))
      who failed to lose weight. For the entire group, mean brachial artery flow
      mediated dilation (FMD) was impaired at 6.7 +/- 4.1%. Following sustained weight
      loss, FMD increased significantly from 6.8 +/- 4.2 to 10.0 +/- 4.7%, but remained
      blunted in patients without weight decline from 6.5 +/- 4.0 to 5.7 +/- 4.1%, P =
      0.013 by ANOVA. Endothelium-independent, nitroglycerin-mediated dilation (NMD)
      was unaltered. BMI fell by 13 +/- 7 kg/m(2) following successful weight
      intervention and was associated with reduced total and low-density lipoprotein
      cholesterol, glucose, hemoglobin A(1c), and high-sensitivity C-reactive protein
      (CRP). Vascular improvement correlated most strongly with glucose levels (r = 
      0.51, P = 0.002) and was independent of weight change. In this cohort of severely
      obese subjects, sustained weight loss at 1 year improved vascular function and
      metabolic parameters. The findings suggest that reversal of endothelial
      dysfunction and restoration of arterial homeostasis could potentially reduce
      cardiovascular risk. The results also demonstrate that metabolic changes in
      association with weight loss are stronger determinants of vascular phenotype than
      degree of weight reduction.

PMID- 20057372
TI  - Diet-induced obesity in two C57BL/6 substrains with intact or mutant nicotinamide
      nucleotide transhydrogenase (Nnt) gene.
AB  - The C57BL/6J (B6/J) male mouse represents a standard for diet-induced obesity
      (DIO) and is unique in expressing a loss-of-function nicotinamide nucleotide
      transhydrogenase (Nnt) gene. This mutation was associated with a marked reduction
      in glucose-stimulated insulin secretion from B6/J islets in vitro and moderately
      impaired glucose clearance in vivo. To assess the contribution of this Nnt
      mutation, we compared DIO responsiveness of Nnt-mutant B6/J males to Nnt wild
      type C57BL/6NJ (B6/NJ) males over a 14-week period of feeding a high-fat (60% of
      calories) diet. Initial mean body weights at 6 weeks did not distinguish the
      substrains and both substrains were DIO-sensitive. However, B6/J males outgained
      the B6/NJ males, with a significant 3 g higher mean body weight at 20 weeks
      accompanied by significant increases in both lean and fat mass. Mean nonfasting
      serum glucose over time was also significantly higher in B6/J males, as was
      impairment of glucose tolerance assessed at 8 and 20 weeks of age. Serum leptin,
      but not insulin, was significantly higher in B6/J males over time. Potential
      contributions of the wild-type Nnt gene were demonstrable on a lower fat diet
      (10% of calories) where a significantly greater weight gain over time by B6/NJ
      males was correlated with a significantly higher serum insulin. In conclusion,
      DIO developed in response to 60% fat feeding regardless of Nnt allele status.
      Contribution of the B6/J-unique Nnt mutation was most evident in response to 10%
      fat feeding that resulted in reduced serum insulin and weight gain compared to
      B6/NJ males.

PMID- 20057373
TI  - Evaluation of a quantitative magnetic resonance imaging system for whole body
      composition analysis in rodents.
AB  - We evaluated the EchoMRI-900 combination rat and mouse quantitative magnetic
      resonance (QMR) body composition method in comparison to traditional whole-body
      chemical carcass composition analysis (CCA) for measurements of fat and fat-free
      mass in rodents. Live and postmortem (PM) QMR fat and lean mass measurements were
      obtained for lean, obese and outbred strains of rats and mice, and compared with
      measurements obtained using CCA. A second group of rats was measured before and
      after 18 h food or water deprivation. Significant positive correlations between
      QMR and CCA fat and lean mass measurements were shown for rats and mice. Although
      all live QMR fat and lean measurements were more precise than CCA for rats,
      values obtained for mice significantly differed from CCA for lean mass only. QMR
      performed PM slightly overestimated fat and lean values relative to live QMR but
      did not show lower precision than live QMR. Food deprivation reduced values for
      both fat and lean mass; water deprivation reduced estimates of lean mass only. In
      summary, all measurements using this QMR system were comparable to those obtained
      by CCA, but with higher overall precision, similar to previous reports for the
      murine QMR system. However, PM QMR measurements slightly overestimated live QMR
      values, and lean and fat mass measurements in this QMR system are influenced by
      hydration status and animal size, respectively. Despite these caveats, we
      conclude that the EchoMRI QMR system offers a fast in vivo method of body
      composition analysis, well correlated to but with greater overall precision than
      CCA.

PMID- 20057374
TI  - Development of an arterio-venous difference method to study the metabolic
      physiology of the femoral adipose tissue depot.
AB  - Gluteofemoral adipose tissue (AT) has interesting positive associations with
      metabolic health, yet little is known of its metabolic physiology. Here, we
      describe a technique for cannulation of a vein draining the femoral fat depot.
      Using ultrasound guidance, a cannula was introduced into a superficial branch of
      the great saphenous vein. We also obtained arterialized blood and, for
      comparison, blood representing drainage from forearm muscle and from subcutaneous
      abdominal AT. We measured appropriate biomarkers of skeletal muscle (creatinine)
      and AT (nonesterified fatty acids (NEFAs), glycerol, leptin) drainage. Blood
      obtained in this way from the saphenous vein did not show creatinine release
      (creatinine concentration 100.5 +/- 0.4%, mean +/- s.e.m., of that in
      arterialized blood), whereas creatinine concentrations in blood draining forearm
      muscle averaged 121 +/- 1% of those in arterialized blood. Fatty acid release
      from the tissue drained was suppressed after feeding and increased during beta
      adrenergic stimulation. We also demonstrated leptin secretion. These findings
      suggest that blood so obtained is representative of AT drainage with little
      apparent contribution of skeletal muscle. We believe this technique will
      facilitate physiological studies of a lower-body fat depot in humans.

PMID- 20057375
TI  - Prepregnancy obesity and risk of stillbirth in viable twin gestations.
AB  - We sought to estimate the impact of prepregnancy obesity on demise of one or both
      fetuses in twin gestations. We performed a retrospective cohort study using the
      Missouri maternally linked cohort files (years 1989-2005). Prepregnancy obesity
      was defined as a BMI >or=30. Outcomes of interest were stillbirth (intrauterine
      fetal death at >or=20 weeks' gestation) and demise of one (partial loss) or both
      (complete loss) fetuses, regardless of the cause. We used Cox Proportional
      Hazards with correction for intracluster correlation to obtain risk estimates.
      The overall stillbirth rate for twin gestations was 15.5/1,000 (18.4/1,000 vs.
      14.5/1,000 in obese and normal weight mothers, respectively; P = 0.02). The rate
      for complete fetal loss was higher in obese mothers (8.3/1,000 vs. 5.6/1,000; P =
      0.01) but was comparable for partial fetal loss (19.1/1,000 for obese vs.
      16.3/1,000 for normal weight mothers; P = 0.1). Adjusted estimates confirmed
      these findings (adjusted hazards ratio (AHR) and 95% confidence interval (CI) =
      1.31 (1.02-1.68) for stillbirth; AHR = 1.59; CI = 1.01-2.51) for complete loss;
      and AHR = 1.21; CI = 0.91-1.62) for partial loss. Subanalysis conducted on
      stillbirth showed that the risk associated with obesity was only elevated for
      same-sex (AHR = 1.54; CI = 1.15-2.04) but not opposite-sex twins (0.99; CI = 0.56
      1.75). Our findings may find utility in counseling of obese women with twin
      gestations.

PMID- 20057376
TI  - Selective alterations within executive functions in adolescents with excess
      weight.
AB  - Increasing evidence underscores overlapping neurobiological pathways to addiction
      and obesity. In both conditions, reward processing of preferred stimuli is
      enhanced, whereas the executive control system that would normally regulate
      reward-driven responses is altered. This abnormal interaction can be greater in
      adolescence, a period characterized by relative immaturity of executive control
      systems coupled with the relative maturity of reward processing systems. The aim
      of this study is to explore neuropsychological performance of adolescents with
      excess weight (n = 27, BMI range 24-51 kg/m(2)) vs. normal-weight adolescents (n
      = 34, BMI range 17-24 kg/m(2)) on a comprehensive battery of executive
      functioning tests, including measures of working memory (letter-number
      sequencing), reasoning (similarities), planning (zoo map), response inhibition
      (five-digit test (FDT)-interference and Stroop), flexibility (FDT-switching and
      trail-making test (TMT)), self-regulation (revised-strategy application test (R
      SAT)), and decision-making (Iowa gambling task (IGT)). We also aimed to explore
      personality traits of impulsivity and sensitivity to reward. Independent sample t
      and Z Kolmogorov-Smirnov tests showed significant differences between groups on
      indexes of inhibition, flexibility, and decision-making (excess-weight
      participants performed poorer than controls), but not on tests of working memory,
      planning, and reasoning, nor on personality measures. Moreover, regression models
      showed a significant association between BMI and flexibility performance. These
      results are indicative of selective alterations of particular components of
      executive functions in overweight adolescents.

PMID- 20057377
TI  - Regular aerobic exercise, without weight loss, improves endothelium-dependent
      vasodilation in overweight and obese adults.
AB  - Lifestyle modification in the form of weight reduction by caloric restriction
      alone or in combination with regular aerobic exercise significantly improves
      endothelium-dependent vasodilation in overweight and obese adults. We determined
      whether regular aerobic exercise, independent of weight loss, improves
      endothelium-dependent vasodilation in overweight and obese adults. Twenty
      overweight and obese adults (age 53 +/- 1 years; BMI: 30.2 +/- 0.8 kg/m(2)) were
      studied before and after a 3-month aerobic exercise training intervention.
      Forearm blood flow (FBF) responses were determined (via plethysmography) in
      response to intra-arterial infusion of acetylcholine and sodium nitroprusside.
      There were no changes in body mass or composition with the intervention. FBF
      responses to acetylcholine were approximately 35% higher (P < 0.01) after (4.1 +/
      0.9 to 14.7 +/- 4.3 ml/100 ml tissue/min) compared with before (4.2 +/- 0.8 to
      11.0 +/- 3 ml/100 ml tissue/min) exercise training. FBF responses to sodium
      nitroprusside were unchanged. These results indicate that regular aerobic
      exercise improves endothelium-dependent vasodilation in overweight and obese
      adults, independent of changes in body mass or composition.

PMID- 20057378
TI  - Psychosocial factors and health perceptions in parents and children who are
      overweight or obese.
AB  - This study examined the relationships among weight status (BMI), health
      perceptions, and psychosocial characteristics in children, parents, and parent
      child dyads. A convenient sample of 114 parent-child dyads participated. All
      children were overweight or obese. Parents and children completed questionnaires
      by self-report or interview. Questionnaires included the Parenting Stress Index
      Short Form (PSI), the Parents' Stage of Change (SOC) Questionnaire, and the
      Pediatric Quality of Life Inventory (PedsQL). Child's mean age was 10.34 years
      (s.d. = 1.87), mean BMI was 28.13 kg/m(2) (s.d. = 5.46), and mean BMI z-score was
      2.17 (s.d. = 0.38). Parent mean age was 37.28 years (s.d. = 12.66) and mean BMI
      was 34.07 kg/m(2) (s.d. = 8.18). Most parents (68.5%) reported that they and
      their children (70.7%) were African American and many (44.3%) reported that they
      and their children were Hispanic. Significant correlations included: child health
      perceptions and child BMI (r = 0.309, P < 0.001) and parent perception of weight
      and parent BMI (r = 0.691, P < 0.001). For parent-child dyads, one correlation
      approached significance (child health perceptions and parent stage of change (r =
      -0.269, P < 0.01). Findings suggest that characteristics of parent-child dyads
      may be important considerations in the management of childhood obesity.

PMID- 20057379
TI  - Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal
      cord of individual mouse embryos.
AB  - Cultured spinal motoneurons are a valuable tool for studying the basic mechanisms
      of axon and dendrite growth and also for analyses of pathomechanisms underlying
      diseases like amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy
      (SMA). As motoneurons in the developing spinal cord of mice constitute only a
      minor population of neurons, these cells need to be enriched in order to study
      them in the absence of contaminating neuronal and non-neuronal cells. Here, we
      describe a protocol for the isolation and in vitro cultivation of embryonic
      primary motoneurons from individual mouse embryos. Tissue dissection, cell
      isolation and a p75(NTR)-antibody-based panning technique, which highly enriches
      motoneurons within <8 h are described. This protocol is aimed to provide an
      alternative to the established FACS-based protocols describing p75(NTR)-based
      enrichments of neurons. This protocol will help in facilitating the research on
      molecular mechanisms underlying motoneuron development, survival and disease
      mechanisms.

PMID- 20057380
TI  - Microwave-assisted synthesis of triple-helical, collagen-mimetic lipopeptides.
AB  - Collagen-mimetic peptides and lipopeptides are widely used as substrates for
      matrix degrading enzymes, as new biomaterials for tissue engineering, as drug
      delivery systems and so on. However, the preparation and subsequent purification
      of these peptides and their fatty-acid conjugates are really challenging. Herein,
      we report a rapid microwave-assisted, solid-phase synthetic protocol to prepare
      the fatty-acid conjugated, triple-helical peptides containing the cleavage site
      for the enzyme matrix metalloproteinase-9 (MMP-9). We employed a PEG-based resin
      as the solid support and the amino acids were protected with Fmoc- and tert-butyl
      groups. The amino acids were coupled at 50 degrees C (25 W of microwave power)
      for 5 min. The deprotection reactions were carried out at 75 degrees C (35 W of
      microwave power) for 3 min. Using this protocol, a peptide containing 23 amino
      acids was synthesized and then conjugated to stearic acid in 14 h.

PMID- 20057381
TI  - Measurement of superoxide dismutase, catalase and glutathione peroxidase in
      cultured cells and tissue.
AB  - Cells contain a large number of antioxidants to prevent or repair the damage
      caused by reactive oxygen species, as well as to regulate redox-sensitive
      signaling pathways. General protocols are described to measure the antioxidant
      enzyme activity of superoxide dismutase (SOD), catalase and glutathione
      peroxidase. The SODs convert superoxide radical into hydrogen peroxide and
      molecular oxygen, whereas the catalase and peroxidases convert hydrogen peroxide
      into water. In this way, two toxic species, superoxide radical and hydrogen
      peroxide, are converted to the harmless product water. Western blots, activity
      gels and activity assays are various methods used to determine protein and
      activity in both cells and tissue depending on the amount of protein required for
      each assay. Other techniques including immunohistochemistry and immunogold can
      further evaluate the levels of the various antioxidant enzymes in tissues and
      cells. In general, these assays require 24-48 h to complete.

PMID- 20057382
TI  - Protocol for the selection of single-domain antibody fragments by third
      generation intracellular antibody capture.
AB  - Single-domain intracellular antibodies are antibody variable segments that bind
      to specific target proteins inside cells. These antigen-binding variable regions
      can interfere with protein function or perturb protein-protein interactions and
      can be used as tools for research, especially functional genomics and proteomics
      and interfering with the protein interactome. This protocol (Intracellular
      Antibody Capture, IAC(3)) describes the isolation of functional variable heavy
      (VH) or variable light (VL) segments from diverse libraries. The protocol
      comprises four principle steps: validation of a bait antigen; initial screening
      in yeast of a single domain library; generation of sub-libraries after the
      initial screen; and finally confirmation of the positive clones interaction with
      antigen in yeast and mammalian cells. Each library (initial, second and third)
      screening takes upto 2 weeks and the overall procedure <3 months. This third
      generation IAC method has many advantages, including isolation of single domain
      intracellular antibodies with high affinity and specificity by direct in vivo
      genetic selection.

PMID- 20057383
TI  - A protocol for generating a high-quality genome-scale metabolic reconstruction.
AB  - Network reconstructions are a common denominator in systems biology. Bottom-up
      metabolic network reconstructions have been developed over the last 10 years.
      These reconstructions represent structured knowledge bases that abstract
      pertinent information on the biochemical transformations taking place within
      specific target organisms. The conversion of a reconstruction into a mathematical
      format facilitates a myriad of computational biological studies, including
      evaluation of network content, hypothesis testing and generation, analysis of
      phenotypic characteristics and metabolic engineering. To date, genome-scale
      metabolic reconstructions for more than 30 organisms have been published and this
      number is expected to increase rapidly. However, these reconstructions differ in
      quality and coverage that may minimize their predictive potential and use as
      knowledge bases. Here we present a comprehensive protocol describing each step
      necessary to build a high-quality genome-scale metabolic reconstruction, as well
      as the common trials and tribulations. Therefore, this protocol provides a
      helpful manual for all stages of the reconstruction process.

PMID- 20057384
TI  - Protocol for solid-phase microextraction method development.
AB  - Solid-phase microextraction (SPME) is a sample preparation method developed to
      solve some of the analytical challenges of sample preparation as well as sample
      introduction and integration of different analytical steps into one system. Since
      its development, the utilization of SPME has addressed the need to facilitate
      rapid sample preparation and integrate sampling, extraction, concentration and
      sample introduction to an analytical instrument into one solvent-free step. This
      achievement resulted in fast adoption of the technique in many fields of
      analytical chemistry and successful hyphenation to continuously developing
      sophisticated separation and detection systems. However, the facilitation of high
      quality analytical methods in combination with SPME requires optimization of the
      parameters that affect the extraction efficiency of this sample preparation
      method. Therefore, the objective of the current protocol is to provide a detailed
      sequence of SPME optimization steps that can be applied toward development of
      SPME methods for a wide range of analytical applications.

PMID- 20057385
TI  - Automated solid-phase microextraction and thin-film microextraction for high
      throughput analysis of biological fluids and ligand-receptor binding studies.
AB  - This protocol describes how to perform automated solid-phase microextraction
      (SPME) and thin-film microextraction (TFME) in a 96-well plate format for high
      throughput analysis of drugs, metabolites and any other analytes of interest in
      biological fluids using liquid chromatography-electrospray tandem mass
      spectrometry. Sample preparation time required is typically 1 min per sample;
      hence, the throughput achievable with automated SPME/TFME is comparable with
      automated 96-well liquid-liquid extraction and solid-phase extraction methods,
      but greater than most online solid-phase extraction methods. The technique is
      applicable to complex samples such as whole blood without additional
      pretreatment. The amount of analyte extracted by SPME/TFME is proportional to the
      free (unbound) concentration of the analyte; hence, SPME/TFME can be used to
      determine both total and free concentrations of analytes from a single biofluid
      sample and to perform automated ligand-receptor binding studies in order to
      determine binding affinity and/or overall extent of ligand binding to a complex
      biofluid.

PMID- 20057386
TI  - Protocol for the development of automated high-throughput SPME-GC methods for the
      analysis of volatile and semivolatile constituents in wine samples.
AB  - Ever since the invention of gas chromatography (GC), numerous efforts within the
      chromatographic community have been directed toward the development of fast GC
      methods. However, the developments in high-speed GC technologies have
      simultaneously created demand for the availability of compatible detection and
      sample preparation methods, so that the speed of the overall analytical process
      is increased. Solid phase micro extraction (SPME) is a sample preparation
      technique developed to address the need for rapid sample preparation. Therefore,
      the objective of this protocol is to outline recent developments in SPME
      technology that can be applied toward high-throughput automated qualitative and
      quantitative analyses of volatile and semivolatile compounds in wine samples. The
      use of this protocol facilitates routine high-throughput determinations of 200
      500 analytes of different physicochemical properties with SPME step requiring
      only 10-15 min per sample.

PMID- 20057388
TI  - Nature Medicine, reloaded.

PMID- 20057387
TI  - A hearing and vestibular phenotyping pipeline to identify mouse mutants with
      hearing impairment.
AB  - We describe a protocol for the production of mice carrying N-ethyl-N-nitrosourea
      (ENU) mutations and their screening for auditory and vestibular phenotypes. In
      comparison with the procedures describing individual phenotyping tests, this
      protocol integrates a set of tests for the comprehensive determination of the
      causes of hearing loss. It comprises a primary screen of relatively simple
      auditory and vestibular tests. A variety of secondary phenotyping protocols are
      also described for further investigating the deaf and vestibular mutants
      identified in the primary screen. The screen can be applied to potentially
      thousands of mutant mice, produced either by ENU or other mutagenesis approaches.
      Primary screening protocols take no longer than a few minutes, apart from ABR
      testing which takes upto 3.5 h per mouse. These protocols have been applied for
      the identification of mouse models of human deafness and are a key component for
      investigating the genes and genetic pathways involved in hereditary deafness.

PMID- 20057389
TI  - Biomarkers still off the mark for detecting breast cancer.

PMID- 20057390
TI  - Embryonic stem cell lines given the go-ahead.

PMID- 20057391
TI  - To boost breast cancer research, a center banks on healthy tissue.

PMID- 20057392
TI  - Better forecasting urged to avoid drug waste.

PMID- 20057394
TI  - Forecast calls for clouds over biological computing.

PMID- 20057395
TI  - Matchmaking service links up researchers to wallflower drugs.

PMID- 20057396
TI  - Algorithms aim to improve hunt for disease markers.

PMID- 20057398
TI  - African networks launch to boost clinical trial capacity.

PMID- 20057399
TI  - In prevention push, AIDS program prioritizes research.

PMID- 20057400
TI  - Pandemic blows lid off laws limiting mercury in vaccines.

PMID- 20057401
TI  - Painkiller concerns grow ahead of new guidelines.

PMID- 20057404
TI  - To save lives, initiative pushes for standardized diagnostic tools.

PMID- 20057405
TI  - For cost effectiveness, real data trumps trial results.

PMID- 20057406
TI  - Institute of Medicine calls for savvier vaccine strategy.

PMID- 20057407
TI  - Britain reevaluates taxes on patent income.

PMID- 20057409
TI  - Bioethicists renew call for changes to prison research.

PMID- 20057411
TI  - Straight talk with... Eric Green. Interview by Erica Westly.
AB  - Eric Green, the new head of the US National Human Genome Research Institute
      (NHGRI), has been involved with genomics since the term was first coined in the
      1980s. He started at the US National Institutes of Health (NIH) as a postdoc and
      was a key contributor to the Human Genome Project. Nearly a decade ago, when
      Green was part of a team that produced one of the first human genome sequences,
      the potential for genomics-related medical applications seemed limitless. But
      most disorders have proved to be too complex to benefit from our current
      understanding of genomics, and some critics have argued that researchers have put
      too much emphasis on uncovering the genetic underpinnings of diseases. Recent
      demand for comparative effectiveness research in medicine has further complicated
      the debate, leading former head of NHGRI Francis Collins to worry that genomic
      differences could get "lost in the wash." Erica Westly spoke with Green about
      where he sees the genomics field heading and what role he thinks the NHGRI should
      have in the American health care system.

PMID- 20057412
TI  - The saving switch.
AB  - The epigenome consists of a system of chemical tags that attach to our DNA and
      its associated molecules, switching genes on and off. But the system is not
      without glitches-and scientists think that the misplacement of these tags can
      cause disease. This idea has led to new drugs that aim to correct gene activity
      (and obliterate disease) by altering the proteins around which DNA winds.
      Cassandra Willyard examines whether this approach will unlock the long-awaited
      promise of epigenetic therapy.

PMID- 20057413
TI  - Drug ads move online, creating a web of regulatory challenges.

PMID- 20057415
TI  - Nicotinamide and neutrophilia.

PMID- 20057417
TI  - Cloaked virus slips between cells.

PMID- 20057418
TI  - Hypertension finds a new rhythm.

PMID- 20057419
TI  - A NOD for autophagy.

PMID- 20057420
TI  - Myelodysplasia: battle in the bone marrow.

PMID- 20057421
TI  - Huntington's disease: tagged for clearance.

PMID- 20057422
TI  - Vessel remodeling in the newborn: platelets fill the gap.

PMID- 20057423
TI  - Migration or evasion.

PMID- 20057425
TI  - Kidney complications: why don't statins always work?

PMID- 20057426
TI  - Kidney complications: factors that protect the diabetic vasculature.

PMID- 20057431
TI  - The use of clinical photography by UK general dental practitioners.
AB  - AIM: The aim of this study was to assess by means of a postal questionnaire the
      numbers of general dental practitioners (GDPs) who used clinical photography and
      for what application. METHOD: The questionnaire was distributed to 1,000 randomly
      selected dentists in the UK with an explanatory letter and reply paid envelope.
      The data collected was computerised and analysed statistically. RESULTS: Five
      hundred and sixty-two replies were received. Of the respondents, 48% used
      clinical photography, with 59% using a digital camera, 34% a 35 mm camera and 19%
      a video camera. Principal uses of clinical photography were treatment planning
      (84%), patient instruction/motivation (75%), medico-legal reasons (71%) and
      communication with the laboratory (64%). CONCLUSION: Clinical photography was
      used by 48% of general dental practitioner respondents.

PMID- 20057432
TI  - Public awareness and social acceptability of dental therapists.
AB  - OBJECTIVES: To investigate public awareness and the social acceptability of
      dental treatment provided by dental therapists in the UK. METHOD: A telephone
      survey of a representative quota sample of 1,000 UK adults. RESULTS: 10.4% of
      participants were aware of dental therapists as a professional group, of whom
      none correctly identified their permitted duties. 61.3% were willing to receive
      simple restorative treatment from a therapist, with acceptability predicted by
      being male [OR 1.44 (95% CI 1.09-1.90)], being younger [OR 1.024 (1.016-1.032)]
      and having a perceived need for treatment [OR 1.49 (1.09-2.5)]. Fewer were
      willing to allow a therapist to restore a child's tooth (54.7%, p <0.001,
      McNemar's test) with acceptability predicted by being younger [OR 1.026 (1.018
      1.034)]. Those receiving some private treatment were less likely to report
      acceptability of simple restorative treatment for themselves [OR 0.61 (0.46
      0.81)] or for children [OR 0.54 (0.41-0.72)]. 48.2% of participants expected to
      pay less for treatment provided by therapists, with acceptability of equal costs
      predicted by the participant being male [OR 1.81 (1.50-2.40)]. CONCLUSION: These
      findings identify a need for education and reassurance of the public on the
      training and permitted duties of dental therapists and the rationale for skill
      mix in dentistry.

PMID- 20057433
TI  - Dentists' professional behavioural characteristics.

PMID- 20057434
TI  - Pseudoseizures and surgery.

PMID- 20057435
TI  - Compact cameras.

PMID- 20057436
TI  - Non-invasive testing.

PMID- 20057437
TI  - Beyond the teeth.

PMID- 20057438
TI  - Duraphat shortage.

PMID- 20057439
TI  - Vaccine to treat gum disease on the way.

PMID- 20057440
TI  - BDA looks forward to Steele progress.

PMID- 20057441
TI  - Successful collaboration scoops prize.

PMID- 20057445
TI  - Dean among 100 influential figures.

PMID- 20057450
TI  - Embedding implants in undergraduate dental education.
AB  - This article represents the consensus from a meeting of the British Society of
      Prosthetic Dentistry's Education Group which met to discuss implant dentistry at
      the undergraduate dental student level. The consensus recognises the need to
      embed the teaching of implant supported prostheses if such a treatment modality
      is to be widely practised after graduation. This short article makes some
      recommendations as well as detailing some challenges and barriers that need to be
      overcome if implant dentistry is to be successfully embedded in an undergraduate
      dental curriculum.

PMID- 20057457
TI  - Developing guidelines for postgraduate dental educators in the UK.
AB  - Commissioned by the UK Committee of Postgraduate Dental Deans and Directors
      (COPDEND), the purpose of this work was to establish UK guidelines for dental
      educators. The final document comprises 79 statements, in eight domains. Each
      domain has four zones related to what dental educators (1) know, (2) do with
      members of the dental team as learners, (3) do with other dental educators as
      learners and (4) lead on. Launched in November 2008, the document provides a
      framework of good practice for use in the employment, development and management
      of dental educators in the UK. The guidelines are readily available from the
      COPDEND website. A key purpose of this paper is to report on the process of
      development and a central part of that was the integration of feedback and
      consultation on early drafts. These processes elicited a total of 102 responses.
      Issues raised in consultation included: (1) how the zones interrelate; (2)
      differentiation between domains; (3) measurability; and (4) implementation
      challenges. This paper includes our responses to these issues.

PMID- 20057458
TI  - Revisiting the supernumerary: the epidemiological and molecular basis of extra
      teeth.
AB  - Supernumerary teeth are a common clinical and radiographic finding and may
      produce occlusal and dental problems. The aetiological basis of extra teeth is
      poorly understood in human populations; however, the mouse provides a useful
      model system to investigate the complex genetics of tooth development. This
      article describes recent advances in our understanding of the genetic basis of
      supernumerary teeth. We have reviewed biological evidence that provides insight
      into why supernumerary tooth formation may occur. Indeed, many of the molecular
      signalling pathways known to be involved in normal development of the tooth germ
      can also give rise to additional teeth if inappropriately regulated. These
      include components of the Hedgehog, FGF, Wnt, TNF and BMP families, which provide
      a useful resource of candidate genes that may potentially play a role in human
      supernumerary tooth formation.

PMID- 20057476
TI  - The Akhonya Dental Project: a new charity aiming to provide oral health education
      and preventative care in Kenya.
AB  - Kenya is a country plagued by HIV and lacking in adequate healthcare resources,
      and despite dental caries remaining the most common disease in the world, there
      is estimated to be only one dentist per 100,000 population in Kenya. Evidence
      suggests that many Kenyans are unaware of the causes of dental disease and half
      of the population are unaware of measures that can be taken to prevent dental
      disease. Oral health education is a clearly vital for improving the health of the
      Kenyan population. The Akhonya Dental Project is a new charity which aims to
      provide oral health education, prevention and treatment for AIDS orphans in rural
      Kenya. This article describes the ethos of the charity and long-term aim to
      increase oral health awareness in the region.

PMID- 20057483
TI  - Prognostic factors for progression of early- and late-stage calcific aortic valve
      disease in Japanese: the Japanese Aortic Stenosis Study (JASS) Retrospective
      Analysis.
AB  - Calcific aortic valve disease (CAVD) is the most common etiology of acquired
      valvular heart disease, and hypertension is a principal underlying disease. The
      Japanese Aortic Stenosis Study (JASS) Retrospective Analysis is a retrospective
      observational study to clarify the prognostic factors for progression of CAVD in
      Japanese. Data from 556 subjects who met the following criteria were analyzed:
      (1) >or=50 years old; (2) calcification in any aortic valve leaflet or peak
      aortic jet velocity >or=2 m s(-1) on an echocardiographic study performed between
      July 2004 and June 2007; and (3) availability of earlier echocardiographic data
      from within the previous 2-5 years to assess the progression of CAVD. The
      subjects were divided into two groups according to CAVD severity on the preceding
      echocardiographic examination. In early-stage subjects with calcification in one
      or zero leaflets who were without aortic stenosis on the preceding
      echocardiographic study (n=157), the prognostic factors for progression were the
      following: (1) no use of angiotensin receptor blockers (ARB) and (2) use of
      warfarin. In late-stage subjects with calcification in two or three leaflets
      and/or aortic stenosis on the preceding echocardiographic study (n=399),
      progression was observed in females and in subjects with low hemoglobin and a
      concentric left ventricle. There was no relation between medications and changes
      in CAVD. Prognostic factors for the progression of CAVD were different between
      the early and late stages. Initiation of ARB treatment during the early stage may
      be effective, and we should be vigilant about progression of CAVD in patients
      treated with warfarin.

PMID- 20057484
TI  - Differences in metal and metalloid content in the hair of normo- and hypertensive
      postmenopausal women.
AB  - This study was performed on scalp hair samples from postmenopausal women (n=26;
      12 normotensives and 14 hypertensives) to determine the relationship between
      blood pressure and metal and metalloids in hair samples. Hair concentrations of
      Al, Ba, Cd, Co, Cr, Mn, Mo, Ni, Pb, Sb, Se, Sr and V were measured using
      inductively coupled plasma mass spectrometry, whereas Ca, Cu, Fe, K, Mg, Na and
      Zn concentrations were measured by inductively coupled plasma optical emission
      spectrometry. Methods were optimized and then validated using certified reference
      material GBW 09101 human hair. Although Cd, Co and Mo levels in hypertensive
      volunteers were significantly higher than in normotensive individuals (P<0.05),
      the concentrations of Fe, Mn, Na (all P<0.05) and K (P<0.001) were significantly
      lower. Concentrations of K (P<0.001; P<0.001) were negatively correlated with
      systolic and diastolic blood pressure. The concentration of Co (P=0.004; P<0.001)
      displayed a positive correlation with both types of pressure, whereas Cu
      (P=0.013) and Ni (P<0.001) concentrations correlated significantly with diastolic
      blood pressure and Mn negatively correlated with systolic blood pressure
      (P=0.031). Overweight and hypertension concurred in 27% of volunteers. This
      concurrence did not modify differences in hair mineral levels attributed to
      hypertension. The present results indicate that scalp hair concentrations of
      certain metals and metalloids can be used as biomarkers for hypertension in
      postmenopausal women.

PMID- 20057485
TI  - Aortic pressure wave reflection in children.
AB  - Aortic pressure wave reflection is one of the risk factors for developing
      cardiovascular disease in adults, and the degree of pressure wave reflection
      increases with aging. However, enhanced pressure wave reflection has also been
      reported in infants and children. The purpose of this study was to clarify
      pressure wave reflection during childhood and to determine the reference for the
      augmentation index, which is one of the most useful parameters used to represent
      the degree of aortic pressure wave reflection in children. This study enrolled 72
      patients with normal aortic circulation. The aortic pressure waveform was
      recorded using a pressure sensor-mounted catheter, and the augmentation index was
      thus calculated. The augmentation index tended to decrease with increasing age
      until around 15 years of age and then increased thereafter. For children below 15
      years of age, multiple regression analysis revealed a significant negative
      correlation between body height and augmentation index. In children, increases in
      aortic pressure wave reflection are probably attributable to changes in body
      height.

PMID- 20057486
TI  - Effects of the AT(1) receptor blocker losartan and the calcium channel blocker
      benidipine on the accumulation of lipids in the kidney of a rat model of
      metabolic syndrome.
AB  - Unfavorable lipid accumulation may occur in the kidneys in the presence of
      metabolic syndrome and diabetes. The aim of this study was to investigate whether
      excess lipids would accumulate in the kidneys of Otsuka Long-Evans Tokushima
      Fatty (OLETF) rats, an animal model of metabolic syndrome. From 34 weeks of age,
      OLETF rats were treated orally with a calcium channel blocker, benidipine (3 mg
      kg(-1) per day), or an AT1 receptor blocker, losartan (25 mg kg(-1) per day), for
      8 weeks. Blood pressure was slightly but significantly higher in the untreated
      OLETF rats (149+/-4 mm Hg) than in Long-Evans Tokushima Otsuka (LETO) rats (136+/
      2 mm Hg), and both losartan (135+/-3 mm Hg) and benidipine (138+/-3 mm Hg)
      reduced blood pressure in OLETF rats to a level comparable to that in LETO rats.
      Tissue content of triglycerides (TG) was greater in OLETF rats than in LETO rats
      (6.24+/-3.77 and 2.85+/-1.32 microg mg(-1) x tissue, respectively), and both
      losartan and benidipine reduced these values. Histological analysis showed lipid
      droplets in tubular cells in which increased dihydroethidium fluorescence was
      present. Expression of peroxisome proliferator-activated receptor-alpha, PGC
      1alpha and uncoupling protein-2 was found to be higher in OLETF rats than in LETO
      rats; however, the expression of these genes was not altered by treatment with
      either antihypertensive drug. In contrast, both losartan and benidipine increased
      the amount of total and phosphorylated forms of AMP kinase and the expression of
      carnitine palmitoyltransferase-1 (CPT-1). In conclusion, treatment of OLETF rats
      with losartan and benidipine reduced the tissue content of TG, decreased the
      production of superoxide and regulated the expression of genes related to fatty
      acid oxidation such as AMP-activated protein kinase and CPT-1 in the kidneys.

PMID- 20057487
TI  - A weapon of endothelial cells for fighting vascular disease.

PMID- 20057488
TI  - Differences in emotional personality traits and stress between sustained
      hypertension and normotension.

PMID- 20057489
TI  - Rosiglitazone prevents the progression of renal injury in DOCA-salt hypertensive
      rats.
AB  - This study was designed to evaluate the possible renoprotective effects of
      rosiglitazone (RGT), a peroxisome proliferator-activated subtype gamma receptor
      agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in
      endogenous endothelin-1 (ET-1) production and renal fibrosis associated with
      inflammation. Rats were implanted with DOCA strips (200 mg kg(-1)) at 1 week
      after unilateral nephrectomy. DOCA-salt rats received control diet with or
      without RGT (10 mg kg(-1) per day). Systolic blood pressure was measured by the
      tail-cuff method. Glomerulosclerosis and tubulointerstitial fibrosis were
      evaluated on kidney sections. The expression of ED-1, cyclooxygenase-2 (COX-2),
      heat shock protein-25 (HSP25) and transforming growth factor-beta1 (TGF-beta1)
      was determined in the kidney by semiquantitative immunoblotting. In DOCA-salt
      rats, systolic blood pressure was increased, whereas creatinine clearance
      decreased compared with controls, which were counteracted by RGT treatment.
      Tubular injury and glomerulosclerois in the histological study were prominent in
      DOCA-salt rats, which were counteracted by RGT treatment. ET-1 expression was
      increased in DOCA-salts rats, which was attenuated by RGT treatment. The
      expression of TGF-beta1, ED-1 and COX-2 was increased in DOCA-salt, which was
      attenuated by RGT treatment. In conclusion, RGT treatment decreases blood
      pressure and is effective in preventing the progression of renal injury in DOCA
      salt hypertension, the mechanisms of which are associated with anti-inflammatory
      and anti-fibrotic effects through reducing the overexpression of ET-1, ED-1, COX
      2 and TGF-beta1 in the kidney.

PMID- 20057490
TI  - Differences in emotional personality traits and stress between sustained
      hypertension and normotension.
AB  - This study was aimed at determining whether there are differences in emotional
      personality traits and psychosocial stress between hypertension and normotension.
      From a large community sample of adults, 14 individuals having hypertension and
      showing clinic blood pressures (BP) >or=140/90 mm Hg and self-measured BPs
      >or=135/85 mm Hg (sustained hypertensives) were selected and compared with a sex-
      and age-matched group of 14 individuals with normotension (clinic BPs <140/90 mm
      Hg and self-measured BPs <135/85 mm Hg) on measures of trait anxiety, trait
      depression, trait anger and stress derived from standardized questionnaires.
      There were no significant differences between hypertensives and normotensives on
      trait anger, but, in line with hypotheses, the sustained hypertensive group
      showed higher levels of trait anxiety, trait depression and stress than did the
      normotensive group. A discriminant analysis revealed that trait depression was
      the most important psychological variable to discriminate between sustained
      hypertension and normotension. Results provide support to the hypothesized
      relationship of emotional personality traits and stress with hypertension, and
      underscore the need to define hypertension on the basis of both clinic and
      home/ambulatory BP measurements and to simultaneously evaluate all relevant
      negative emotional constructs, when conducting research on psychological factors
      in hypertension.

PMID- 20057491
TI  - Parkinson disease: Another player in gene therapy for Parkinson disease.

PMID- 20057492
TI  - Stroke: Intervention in carotid stenosis--is the issue resolved?

PMID- 20057493
TI  - Prion disease: Brain MRI studies in prion disease.

PMID- 20057494
TI  - Alzheimer disease: New light on an old CLU.

PMID- 20057495
TI  - Pain: Noninvasive functional neurosurgery using ultrasound.

PMID- 20057497
TI  - The clinical approach to movement disorders.
AB  - Movement disorders are commonly encountered in the clinic. In this Review, aimed
      at trainees and general neurologists, we provide a practical step-by-step
      approach to help clinicians in their 'pattern recognition' of movement disorders,
      as part of a process that ultimately leads to the diagnosis. The key to success
      is establishing the phenomenology of the clinical syndrome, which is determined
      from the specific combination of the dominant movement disorder, other abnormal
      movements in patients presenting with a mixed movement disorder, and a set of
      associated neurological and non-neurological abnormalities. Definition of the
      clinical syndrome in this manner should, in turn, result in a differential
      diagnosis. Sometimes, simple pattern recognition will suffice and lead directly
      to the diagnosis, but often ancillary investigations, guided by the dominant
      movement disorder, are required. We illustrate this diagnostic process for the
      most common types of movement disorder, namely, akinetic-rigid syndromes and the
      various types of hyperkinetic disorders (myoclonus, chorea, tics, dystonia and
      tremor).

PMID- 20057496
TI  - Disease and the brain's dark energy.
AB  - Brain function has traditionally been studied in terms of physiological responses
      to environmental demands. This approach, however, ignores the fact that much of
      the brain's energy is devoted to intrinsic neuronal signaling. Recent studies
      indicate that intrinsic neuronal activity manifests as spontaneous fluctuations
      in the blood oxygen level-dependent (BOLD) functional MRI (fMRI) signal. The
      study of such fluctuations could potentially provide insight into the brain's
      functional organization. In this article, we begin by presenting an overview of
      the strategies used to explore intrinsic neuronal activity. Considering the
      possibility that intrinsic signaling accounts for a large proportion of brain
      activity, we then examine whether the functional architecture of intrinsic
      activity is altered in neurological and psychiatric diseases. We also review a
      clinical application of brain mapping, in which intrinsic activity is employed
      for the preoperative localization of functional brain networks in patients
      undergoing neurosurgery. To end the article, we explore some of the basic science
      pursuits that have been undertaken to further understand the physiology behind
      intrinsic activity as imaged with BOLD fMRI.

PMID- 20057498
TI  - INPH and Parkinson disease: differentiation by levodopa response.
AB  - Differentiating between Parkinson disease (PD) and idiopathic normal pressure
      hydrocephalus (INPH) can be challenging for the practicing clinician. Patients
      with undiagnosed PD but with incidental ventriculomegaly run the risk of being
      subjected to unnecessary shunt surgery. Taking a family history of PD and
      establishing the presence of motor symptoms (tremor, rigidity, bradykinesia) and
      nonmotor symptoms could help to differentiate between the two disorders. For
      patients with parkinsonian features, a dopamine challenge test to exclude the
      possibility of idiopathic PD might be beneficial. In this article, we highlight
      the difficulty of accurately differentiating INPH from PD as illustrated by three
      clinical cases of patients referred for shunt surgery.

PMID- 20057500
TI  - Noninvasive molecular imaging of apoptosis in vivo using a modified firefly
      luciferase substrate, Z-DEVD-aminoluciferin.
AB  - Apoptosis is a highly regulated process of programmed cell death essential for
      normal physiology. Dysregulation of apoptosis contributes to the development and
      progression of various diseases, including cancer, neurodegenerative disorders,
      and chronic heart failure. Quantitative noninvasive imaging of apoptosis in
      preclinical models would allow for dynamic longitudinal screening of compounds
      and facilitates a more rapid determination of therapeutic efficacy. In this
      study, we report the in vivo characterization of Z-DEVD-aminoluciferin, a
      modified firefly luciferase substrate that in apoptotic cells is cleaved by
      caspase-3 to liberate aminoluciferin, which can be consumed by luciferase to
      generate a luminescent signal. In two oncology models, namely SKOV3-luc and MDA
      MB-231-luc-LN, at 24, 48, and 72 h after treatment with docetaxel, animals were
      injected with Z-DEVD-aminoluciferin and bioluminescent images were acquired.
      Significantly more light was detected at 24 (P<0.05), 48 (P<0.01), and 72 h
      (P<0.01) in the docetaxel-treated group compared with the vehicle-treated group,
      with caspase-3 activation at these time points confirmed using
      immunohistochemistry. Importantly, whereas significant differences between groups
      were detected as early as 24 h after treatment by molecular imaging, caliper
      measurements were unable to detect a difference for 4-5 additional days. Taken
      together, these data show that in vivo imaging of apoptosis using Z-DEVD
      aminoluciferin could provide a sensitive and rapid method for early detection of
      drug efficacy, which could potentially be used by numerous therapeutic programs.

PMID- 20057499
TI  - BUB3 that dissociates from BUB1 activates caspase-independent mitotic death
      (CIMD).
AB  - The cell death mechanism that prevents aneuploidy caused by a failure of the
      spindle checkpoint has recently emerged as an important regulatory paradigm. We
      previously identified a new type of mitotic cell death, termed caspase
      independent mitotic death (CIMD), which is induced during early mitosis by
      partial BUB1 (a spindle checkpoint protein) depletion and defects in kinetochore
      microtubule attachment. In this study, we have shown that survived cells that
      escape CIMD have abnormal nuclei, and we have determined the molecular mechanism
      by which BUB1 depletion activates CIMD. The BUB3 protein (a BUB1 interactor and a
      spindle checkpoint protein) interacts with p73 (a homolog of p53), specifically
      in cells wherein CIMD occurs. The BUB3 protein that is freed from BUB1 associates
      with p73 on which Y99 is phosphorylated by c-Abl tyrosine kinase, resulting in
      the activation of CIMD. These results strongly support the hypothesis that CIMD
      is the cell death mechanism protecting cells from aneuploidy by inducing the
      death of cells prone to substantial chromosome missegregation.

PMID- 20057501
TI  - Negative regulation of diacylglycerol kinase theta mediates adenosine-dependent
      hepatocyte preconditioning.
AB  - In liver ischemic preconditioning (IP), stimulation of adenosine A2a receptors
      (A2aR) prevents ischemia/reperfusion injury by promoting diacylglycerol-mediated
      activation of protein kinase C (PKC). By concerting diacylglycerol to
      phosphatidic acid, diacylglycerol kinases (DGKs) act as terminator of
      diacylglycerol signalling. This study investigates the role of DGK in the
      development of hepatocyte IP. DGK activity and cell viability were evaluated in
      isolated rat hepatocytes preconditioned by 10 min hypoxia followed by 10 min re
      oxygenation or by the treatment with the A2aR agonist, CGS21680, and subsequently
      exposed to prolonged hypoxia. We observed that after IP or A2aR activation, a
      decrease in DGK activity was associated with the onset of hepatocyte tolerance to
      hypoxia. CGS21680-induced stimulation of A2aR specifically inhibited DGK isoform
      theta by activating RhoA-GTPase. Consistently, both siRNA-mediated downregulation
      of DGK theta and hepatocyte pretreatment with the DGK inhibitor R59949 induced
      cell tolerance to hypoxia. The pharmacological inhibition of DGK was associated
      with the diacylglycerol-dependent activation of PKC delta and epsilon and of
      their downstream target p38 MAPK. In conclusion, we unveil a novel signalling
      pathway contributing to the onset of hepatocyte preconditioning, which through
      RhoA-GTPase, couples A2aR to the downregulation of DGK. Such an inhibition is
      essential for the sustained accumulation of diacylglycerol required for
      triggering PKC-mediated survival signals.

PMID- 20057502
TI  - Reciprocal epigenetic modification of histone H2B occurs in chromatin during
      apoptosis in vitro and in vivo.
AB  - Histone H2B phosphorylation at Serine 14 (phosS14) has been proposed as an
      epigenetic marker of apoptotic cells, whereas acetylation at the adjacent Lysine
      15 (acK15) is a property of non-dying cells. We investigated the relationship and
      the potential regulatory mechanisms between these two epigenetic histone
      modifications and internucleosomal DNA degradation during apoptosis. Using rat
      primary thymocytes induced to undergo apoptosis with glucocorticoids we found
      that H2B phosphorylated at Ser14 was associated with soluble, cleaved DNA in
      apoptotic nuclei. In contrast acK15 was prevalent in non-apoptotic nuclei and
      scarce in apoptotic nuclei. This switch between K15 acetylation and S14
      phosphorylation on H2B was also observed in apoptotic thymocytes from animals
      treated in vivo with glucocorticoids and in a rat hepatoma cell line (HTC)
      induced to die by UV-C or Fas ligand. It is interesting to note that the combined
      use of a histone deacetylase inhibitor and glucocorticoid suppressed both S14
      phosphorylation and internucleosomal DNA degradation without inhibiting apoptosis
      in thymocytes. Using synthetic peptides and a PKC phosphorylation assay system,
      we show that the deacetylation of K15 was necessary to allow the S14
      phosphorylation. These findings suggest that selective chromatin post
      translational modifications are associated with DNA degradation during apoptosis.

PMID- 20057503
TI  - The Parkinson-associated protein PINK1 interacts with Beclin1 and promotes
      autophagy.
AB  - Mutations in the PINK1 gene cause autosomal recessive Parkinson's disease. The
      PINK1 gene encodes a protein kinase that is mitochondrially cleaved to generate
      two mature isoforms. In addition to its protective role against mitochondrial
      dysfunction and apoptosis, PINK1 is also known to regulate mitochondrial dynamics
      acting upstream of the PD-related protein Parkin. Recent data showed that
      mitochondrial Parkin promotes the autophagic degradation of dysfunctional
      mitochondria, and that stable PINK1 silencing may have an indirect role in
      mitophagy activation. Here we report a new interaction between PINK1 and Beclin1,
      a key pro-autophagic protein already implicated in the pathogenesis of
      Alzheimer's and Huntington's diseases. Both PINK1 N- and C-terminal are required
      for the interaction, suggesting that full-length PINK1, and not its cleaved
      isoforms, interacts with Beclin1. We also demonstrate that PINK1 significantly
      enhances basal and starvation-induced autophagy, which is reduced by knocking
      down Beclin1 expression or by inhibiting the Beclin1 partner Vps34. A mutant,
      PINK1(W437X), interaction of which with Beclin1 is largely impaired, lacks the
      ability to enhance autophagy, whereas this is not observed for PINK1(G309D), a
      mutant with defective kinase activity but unaltered ability to bind Beclin1.
      These findings identify a new function of PINK1 and further strengthen the link
      between autophagy and proteins implicated in the neurodegenerative process.

PMID- 20057505
TI  - A genome-wide scan of male sexual orientation.

PMID- 20057504
TI  - Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate
      from Bcl-2.
AB  - The antiapoptotic proteins Mcl-1 and Bcl-2 have been shown to be critical in T
      cell development and homeostasis, but the precise mechanism by which these
      proteins function in T cells and other cells of the body is unclear. Potential
      mechanisms have allowed both for overlapping and unique roles for these proteins
      because of their abilities to bind different proapoptotic Bcl-2 family members,
      but it is unclear which of these mechanisms are important in an in vivo context.
      By generation of various genetic mouse models, we found that Mcl-1-deficient
      thymocytes die largely by a Bak-specific mechanism. In vivo deletion of Bak
      rescued the survival and developmental blocks of Mcl-1-deficient thymocytes at
      the double-negative and single-positive stages. Transgenic overexpression of Bcl
      2 and in vivo deletion of Bax or Bim were unable to rescue Mcl-1-deficient
      thymocytes. Thus, Mcl-1 functions in a unique pathway from Bcl-2 in T
      lymphocytes, likely because of its specific ability to bind and sequester
      proapoptotic Bak. Together, these data provide an in vivo model for Mcl-1
      activity and present us with a greater understanding of the pathways that promote
      thymocyte survival.

PMID- 20057506
TI  - Polymorphism screening of brain-expressed FABP7, 5 and 3 genes and association
      studies in autism and schizophrenia in Japanese subjects.
AB  - Fatty acid-binding protein (FABP) gene family encode fatty acid-binding proteins
      and consist of at least 12 members, of which FABP7, 5 and 3 are expressed in the
      brain. We previously showed that FABP7 is associated with schizophrenia and
      bipolar disorder. Recently, genetic overlap between autism and schizophrenia has
      been reported. Therefore, in this study, we set out to examine the possible roles
      of brain-expressed FABPs in autism, focusing primarily on potentially functional
      polymorphisms (that is, missense polymorphisms). First, we resequenced the three
      genes using 285 autism samples. We identified 13 polymorphisms, of which 7 are
      novel. Of the novel single-nucleotide polymorphisms (SNPs), two are missense
      mutations, namely, 376G>C (Val126Leu) in FABP7 and 340G>C (Gly114Arg) in FABP5.
      Second, we tested for the genetic association of four missense SNPs with autism
      and schizophrenia, but failed to detect significant results. Finally, as a web
      based algorithm predicts that the 8A>G (Asp3Gly; rs17848124) in FABP3 is
      'probably damaging', we estimated the possible impact of this SNP, and found that
      the loss of charge and salt bridge, caused by the Asp3-to-Gly3, may affect
      stability of the FABP3 protein. Future searches for associated phenotypes with
      missense SNPs using larger samples are highly warranted.

PMID- 20057507
TI  - Influencing factors on the suitability of organ-cultured corneas.
AB  - PURPOSE: To determine the factors related to donor and tissue retrieval, which
      influence the suitability of organ-cultured corneas for transplantation. PATIENTS
      AND METHODS: We retrospectively analysed 2596 donor corneas. Polytomic logistic
      regression analysis was used to assess the influence of various factors (that is,
      donor age, cause of death, death-to-tissue retrieval time, tissue retrieval-to
      reception time, and tissue retrieval method) on the suitability of grafts for
      transplantation. Positive predictive values (PPVs) were computed. RESULTS: Forty
      three percent (1118/2596) of corneas were discarded. The leading cause for
      discarding corneas was poor endothelial quality (21.5%). Corneas from donors
      older than 80 years were more likely to be discarded because of endothelial
      insufficiency (OR=2.37, P=0.001). Longer time between death and tissue retrieval
      was associated with increased risk of positive serology (OR=1.43, P=0.02).
      Increased time between tissue retrieval and reception was associated with
      increased risk of contamination (OR=1.57, P=0.03). PPV increased from 38.5% for
      corneas retrieved from donors older than 80 years featuring a death-to-tissue
      retrieval time of more than 6 h and a tissue retrieval-to-reception time of more
      than 24 h to 64.7% for corneas retrieved from donors younger than 80 years
      featuring a death-to tissue retrieval time shorter than 6 h and a tissue
      retrieval-to-reception time shorter than 24 h. CONCLUSION: The percentage of
      discarded corneas can be reduced by including donors aged 80 years or less, using
      a time from donor's death to tissue retrieval shorter than 6 h, and a tissue
      retrieval-to-reception time shorter than 24 h.

PMID- 20057508
TI  - Trabeculectomy pearls of wisdom; mitomycin-soaked pledget 'necklace' suture.

PMID- 20057509
TI  - Why do patients still require surgery for the late complications of Proliferative
      Diabetic Retinopathy?
AB  - AIM: To briefly review and discuss the literature on why patients still require
      surgery for the late complications of proliferative diabetic retinopathy (PDR).
      METHODS: Literature review. RESULTS: The reasons for incomplete coverage of
      screening and screening failures can be divided into non-modifiable and
      potentially modifiable risk factors. The non-modifiable group includes duration
      of diabetes, age, genetic predisposition, ethnic differences, and the various
      reasons for vitrectomy when optimum laser treatment has been applied at the
      appropriate stage of the disease process. The potentially modifiable group
      includes glycaemic control, blood pressure control, lipid control, and cessation
      of smoking in type 1 diabetes. Other potentially modifiable factors include
      adequacy of screening, including reaching the regular non-attender, and
      attempting to modify the psychological factors that lead to late presentations
      including depression and eating disorders. Other potentially modifiable risk
      factors are optimising laser treatments and the potential use of anti-VEGF
      therapy to prevent vitrectomy in iris neovascularisation and neovascular
      glaucoma. CONCLUSION: Surgery for the late complications of PDR continues to be
      required even in some patients who have received optimal medical care and optimal
      laser treatment. There are certain modifiable risk factors that could be altered
      and further research is needed in specific fields, particularly with regard to
      the adequacy of laser treatments, the use of anti-VEGF agents in iris
      neovascularisation, and in the role of psychological support in reducing the type
      of late complications leading to surgery for PDR.

PMID- 20057510
TI  - A novel technique using spectral-domain optical coherence tomography (Spectralis,
      SD-OCT+HRA) to image supine non-anaesthetized infants: utility demonstrated in
      aggressive posterior retinopathy of prematurity.
AB  - PURPOSE: To acquire high definition spectral domain optical coherence tomography
      (SD-OCT) images of supine, non-anesthetized infants in the office by a novel
      modification of a commercially available table-top, chin rest system. METHOD:
      Spectralis, a combined HRA+OCT device (Heidelberg Engineering, Heidelberg,
      Germany) was modified to convert the table-top system into a hand-held device
      using a two-step modification of the existing system. This device was used to
      obtain high-resolution OCT images of four infants with aggressive posterior
      retinopathy of prematurity (APROP) who required no general anesthesia. RESULTS:
      Serial imaging at two time periods of the exact area of clinical interest were
      obtained and were comparable. The entire procedure was safely completed in the
      office. The obtained OCT images guided selective laser ablation of flat
      neovascularization which were missed on clinical examination. CONCLUSION: With
      this simple modification and technique, the ability of using the Spectralis, a
      popular combined angiography and OCT imaging device for imaging supine, non
      anesthetized infants has been established. This possibility would allow the dual
      use of the table-top system to serve also as a hand-held device for paediatric
      cases that can be imaged in the office setting with limited operating room
      facility in a busy practice.

PMID- 20057511
TI  - Neovascular age-related macular degeneration: decision making and optimal
      management.
AB  - AIM: To review the decision-making processes and dilemmas in the delivery of
      services for neovascular age-related macular degeneration (nAMD) and describe its
      optimal management. METHODS: Review of literature and presentation of
      illustrative cases. RESULTS: Guidelines are available to aid commissioners and
      providers of services but with important gaps in advice. Increasing awareness of
      variants and diseases that mimic nAMD means that clinicians need to carefully
      assess lesions at presentation, using stereo imaging, fluorescein and indocyanine
      green angiography, and new generation optical coherence tomography. Current
      evidence supports the use of ranibizumab as first-line therapy. Evidence is
      unclear on the most appropriate treatment regime, especially in protocols relying
      on clinician-determined re-treatment. Current consensus recommends initiation
      with monthly injections for 3 months followed by maintenance comprising regular
      monthly visits with clinician-determined re-treatment. Further evidence on
      treatment protocols and the comparison with bevacizumab is awaited. CONCLUSIONS:
      Owing to incomplete evidence base health professionals face a large number of
      controversies and dilemmas in care pathways for patients with nAMD. Treatment
      should be delivered against protocols developed locally in a systematic manner
      with consensus and a cautious approach to change.

PMID- 20057512
TI  - Pars plana vitrectomy in the management of paediatric uveitis: the Massachusetts
      Eye Research and Surgery Institution experience.
AB  - PURPOSE: To assess the effectiveness and safety of pars plana vitrectomy (PPV) in
      the management of chronic paediatric uveitis. METHODS: We reviewed records of
      patients 16 years old or younger who underwent PPV due to persistent uveitis.
      Data including inflammatory status, ocular findings, visual acuity, dosage and
      duration of various medical therapies, surgical techniques and complications were
      collected. RESULTS: Twenty-eight eyes of 20 patients were included in the study.
      The diagnoses of uveitis included pars planitis in 15 eyes (54%), idiopathic
      panuveitis in 8 eyes (29%), and juvenile idiopathic arthritis-associated
      iridocyclitis in five eyes (18%). Six eyes presented with associated retinal
      vasculitis. The mean age at the time of PPV was 11.2 years. The mean follow-up
      after surgery was 13.5 months. All 28 eyes had active uveitis with or without
      medical therapy at the time of PPV. At last follow-up, uveitis control was
      achieved with or without adjuvant medical therapy in 27 eyes (96%). These
      included five of the six eyes with persistent retinal vasculitis. Two eyes that
      had 20-G PPV developed intra-operative retinal tears. Four eyes with pre
      operative clear lenses developed cataract within the first 6 months after PPV.
      CONCLUSIONS: PPV is effective and safe in the management of chronic paediatric
      uveitis and its complications. It was able to reduce the amount of systemic
      medications required to control inflammation in this study. Patients with uveitis
      complicated by retinal vasculitis, however, are more likely to require long-term
      medical therapy to achieve inflammatory control.

PMID- 20057513
TI  - Verticilide, a new ryanodine-binding inhibitor, produced by Verticillium sp. FKI
      1033.
AB  - A new ryanodine-binding inhibitor, verticilide, was isolated from the cultured
      broth of a fungus, Verticillium sp. FKI-1033. It is a 24-membered ring cyclic
      depsipeptide, its structure being elucidated as cyclo[(2R)-2-hydroxyheptanoyl-N
      methyl- L-alanyl](4). Verticilide inhibited ryanodine binding to ryanodine
      receptors in the cockroach at an IC(50) value of 4.2 microM, whereas inhibition
      against mouse ryanodine receptors was weak (IC(50)=53.9 microM).

PMID- 20057514
TI  - Protoplast preparation and reversion to the normal filamentous growth in
      antibiotic-producing uncommon actinomycetes.
AB  - Protoplast preparation, regeneration and fusion represent essential tools for
      those poorly studied biotechnologically valuable microorganisms inapplicable with
      the current molecular biology protocols. The protoplast production and
      regeneration method developed for Planobispora rosea and using the combination of
      hen egg-white lysozyme (HEWL) and Streptomyces globisporus mutanolysin was
      applied to a set of antibiotic-producing filamentous actinomycetes belonging to
      the Streptosporangiaceae, Micromonosporaceae and Streptomycetaceae. 10(7)-10(9)
      protoplasts were obtained from 100 ml of culture, after incubation times in the
      digestion solution ranging from a few hours to 1 or 2 days depending on the
      strain. The efficiency of protoplast reversion to the normal filamentous growth
      varied from 0.1 to nearly 50%. Analysis of cell wall peptidoglycan in three
      representative strains (Nonomuraea sp. ATCC 39727, Actinoplanes teichomyceticus
      ATCC 31121 and Streptomyces coelicolor A3(2)) has evidenced structural variations
      in the glycan strand and in the peptide chain, which may account for the
      different response to cell digestion and protoplast regeneration treatments.

PMID- 20057515
TI  - Walkmycin B targets WalK (YycG), a histidine kinase essential for bacterial cell
      growth.
AB  - The WalK (a histidine kinase)/WalR (a response regulator, aka YycG/YycF) two
      component system is indispensable in the signal transduction pathway for the cell
      wall metabolism of Bacillus subtilis and Staphylococcus aureus. The inhibitors
      directed against WalK would be expected to have a bactericidal effect. After we
      screened 1368 culture broths of Streptomyces sp. by a differential growth assay,
      walkmycin A, B and C, which were produced by strain MK632-100F11, were purified
      using silica-gel column chromatography and HPLC. In this paper, the chemical
      structure of the major product (walkmycin B) was determined to be di-anthracenone
      (C(44)H(44)Cl(2)O(14)), which was very similar to BE40665A. MICs of walkmycin B
      against B. subtilis and S. aureus were 0.39 and 0.20 microg ml(-1), and IC(50)
      measurements against WalK were 1.6 and 5.7 microM, respectively. To clarify the
      affinity between WalK and walkmycin B, surface plasmon resonance was measured to
      obtain the equilibrium dissociation constant, K(D1), of 7.63 microM at the higher
      affinity site of B. subtilis WalK. These results suggest that walkmycin B
      inhibits WalK autophosphorylation by binding to the WalK cytoplasmic domain.

PMID- 20057516
TI  - On "Microwave models of optical resonators".

PMID- 20057517
TI  - Metric centennial.

PMID- 20057519
TI  - Optical activities in the universities.

PMID- 20057518
TI  - The metric system in the electrical industry.

PMID- 20057520
TI  - From finger counting to the metric system.

PMID- 20057521
TI  - Refrigeration for photomultipliers.
AB  - A closed-cycle mechanical refrigeration system has been adapted to cool
      photomultipliers automatically. Temperature is adjustable between +50 degrees and
      -55 degrees C and is stable to within +/-0.30 degrees C. An important feature of
      the design is the flexible connection to the cold box which allows extensive
      freedom of motion; this freedom is particularly important in astronomy where the
      cold box is mounted on the end of a telescope. Liquid Freon refrigerants have
      been used to cool photomultipliers for rocket flights. A brief description of two
      methods is given.

PMID- 20057522
TI  - Of optics and opticists.

PMID- 20057523
TI  - Accurate method for determining photometric linearity.
AB  - Accurate photometric measurements depend on the linearity of the detection
      system, i.e., whether the output is strictly proportional to the incident light
      flux. The usual method for checking linearity is to introduce filters of known
      absorption into the optical path. Unfortunately, the many possible errors
      inherent in this method make it difficult to determine linearity in this way to
      better than 1%. By using three polarizers in series, keeping the axes of the
      outer two parallel and rotating the middle polarizer, it is possible to eliminate
      most of these sources of error. If polarizers of the highest quality are used,
      photometric linearity may be determined to better than 0.1%. Accurate values for
      the transmission of standard filters can also be determined with this instrument.
      The technique is particularly useful for calibrating filters having large optical
      densities. An error analysis and some experimental results obtained using a three
      polarizer system are given.

PMID- 20057524
TI  - Radiant emission characteristics of a nonisothermal spherical cavity.
AB  - An equation is derived that relates the emissivity of a spherical cavity to the
      temperature distribution along the axis normal to the opening. The mathematical
      formulation of the problem rests on De Vos's method, and is carried out exactly,
      by means of a suitable serial development. The solution enables one to estimate
      the influence of the temperature gradient on the radiant emission of the
      reference spherical blackbody.

PMID- 20057525
TI  - Determination of the spectral emission of commercial flashbulbs by emission
      spectrographic techniques.
AB  - The relative energy distributions of the M-2, P-25, AG-1, and M-3 flashbulbs have
      been determined over the spectral range from 3400 A to 7600 A, using a National
      Bureau of Standards lamp as a spectral standard, and a Jarrell-Ash Ebert-mount
      spectrograph as a spectroradiometer. From these data and the blackbody radiation
      function, values for the color temperature of the flashbulbs have been calculated
      using a computer to derive a least-squares, best-fit value of color temperature.

PMID- 20057526
TI  - A useful infrared source.
AB  - Reliable Inconel-sheathed cartridge heaters rated at hundreds or thousands of
      watts have been in use for many years. Miniature heaters have been manufactured,
      having axial leads, which when treated with an emissive coating meet or exceed
      Globar emissivities in the ir. Free-air temperatures approximating 800 degrees C
      have been obtained for power inputs of 10 W, while temperatures as high as 1150
      degrees C are possible for short lifetimes, e.g., 10 h, at power dissipations of
      24 W or more. Sources can be designed to operate from d or ac power with higher
      voltages and lower currents depending upon physical size limitations, resulting
      in simplified power supply problems. Although voltages from 12 V to 230 V are
      practical for larger units, the sources described below operated at 1060 degrees
      C from a nominal 1.07 A at 18.7 V d for apower consumption of 20 W variable
      continuously about this value. The small dimensions of these sources compare
      favorably to those of a 0.5-W electronic resistor. The present units are
      cylindrical, 1 cm long x 4 mm diam. The construction of smaller units is possible
      bt difficult under present state-of-the-art limitations.

PMID- 20057527
TI  - On the question of equilibrium in mercury + thallium iodide arc discharges.
AB  - Two aspects of the concept of local thermodynamic equilibrium are examined in
      mediumpressure, mercury arc discharges with thallium iodide additives. It is
      shown theoretically that the experimental intensity of the T 5350 A line is
      reasonably consistent with a Boltzmann distribution of excited states. In fact,
      it is theoretically and experimentally shown that self-absorption is a major
      factor in limiting the intensity of the bright thallium 5350 A line even though
      Ti is a minor constituent in the discharge and even though this line does not
      terminate on the ground state. The dramatic spectral inhomogeneity that develops
      in long, horizontal, ac discharges with excess TII in the presence of a
      longitudinal temperature gradient is examined in detail. Both emission and
      absorption studies show that the spectral inhomogeneity is caused by a large
      gradient in the thallium concentration. This inhomogeneous distribution of TlI
      vapors is caused by an inhomogeneous and unsymmetrical distribution of condensed
      THI along the tube walls which results from the temperature gradient. In turn,
      the temperature gradient is increased by the ionization of thallium which locally
      decreases the electrical resistivity, electric field, and power input to the arc.
      Thus, an equilibrium distribution of TlI vapors is attained only if the
      distribution of condensed TlI is reasonably uniform and the tube geometry and
      pressure are favorable for rapid diffusion of the vapors. The inhomogeneity also
      disappears if a sufficiently small quantity of solid TII is added to the lamp so
      that it is all vaporized.

PMID- 20057528
TI  - A high time resolution polarimeter for laser analysis.
AB  - A technique that has a time resolution capability of better than 0.1 microsec has
      been developed for the measurement of the polarization of a light beam. This
      technique has proven useful in measuring the polarization of pulsed laser beams
      because changes in polarization from spike to spike also may be measured. In
      essence, the method of measurement is to split the beam into identical components
      and to pass these components through various polarization analyzers at different
      angles. The intensity of the beams after passing through the analyzers is
      measured by photomultipliers, and the output of the photomultipliers are recorded
      on oscilloscopes.

PMID- 20057530
TI  - Metric matters.

PMID- 20057529
TI  - Automatic control of the spacing of Fabry-Perot interferometers.
AB  - The automatic control of the spacing of Fabry-Perot interferometers to transmit
      at a given wavelength is discussed, and an interferometer is described in which
      the plates are maintained parallel to within the accuracy of the plates
      themselves and at a preset spacing. The variation in mean spacing over test
      periods of several hours has not exceeded +/- 0.7 nm despite temperature
      fluctuations and other uncontrolled environmental conditions.

PMID- 20057531
TI  - Holographic data storage in three-dimensional media.
AB  - The holographic storage of diffraction patterns in a three-dimensional media is
      described from a vector viewpoint derived from the Kirchhoff diffraction
      integral. The sensitivity of the reconstruction to wavelength and to the
      orientation of the readout beam is calculated, and experimental results are
      given.

PMID- 20057533
TI  - Artificial diffraction anomalies for gratings of rectangular profile.
AB  - Wood's anomalies are investigated by using a microwave spectrometer operating at
      a wavelength of 3.8 mm. For S-polarization, high surface conductivity,
      periodicities of 2lambda and 3lambda, and groove depths from lambda/8 to
      (5lambda)/4, rectangular profile gratings are shown to exhibit anomalies which
      can be explained by simple interference between the orders due to the incident
      beam and the orders due to the passing-off order if it is considered as a second
      beam incident at +/-90 degrees . Artificial passing-off orders are formed, and
      these permit one to change the natural anomalies from bright to dark and vice
      versa. Interference of the orders owing to the incident and imposed beams at
      anomalous angles is demonstrated by measuring the power in each of the
      overlapping orders separately and comparing the sum of their amplitudes with the
      value measured at the anomalous angle. For all cases tested the results are
      satisfactory for either bright or dark anomalies. By adjusting the angle of a
      second incident beam to calculated values, artificial anomalies, i.e., anomalies
      at angles of incidence where they do not normally occur, are created. These
      anomalies cannot be distinguished from their natural counterparts.

PMID- 20057534
TI  - Optical activities in industry.

PMID- 20057535
TI  - An experimental study of the dynamics of fiber optic bundles.
AB  - An experimental investigation was made to establish the feasibility of using a
      flexible fiber optics bundle in a dynamic application. It is shown that, by
      controlling its configuration during motion, it is possible to oscillate one end
      of the bundle at high speeds over a large excursion. With reinforced bundle
      sheathing, speeds as high as 7 c/s have been achieved without any defects after 2
      x 10(6) c/s. Possible applications of this type of moving fiber bundle are in
      printing, scanning, display, and photocomposing. In addition to other system
      advantages gained from its use in these areas, a flexible fiber bundle is not
      limited by field coverage as are conventional optical systems.

PMID- 20057536
TI  - Image velocity sensing by optical correlation.
AB  - The technique of measuring the velocity of a moving image by means of a parallel
      slit spatial filter is treated as continuous optical correlation processing. This
      technique is compared with other approaches to measuring image velocity by
      correlation and is shown to be a special case where the image displacement
      necessary for the correlation measurement is held constant and the time interval
      required to traverse this fixed distance is measured. The time measurement is
      accomplished inherently in terms of the frequency of the periodic signal
      generated by the image motion. Based on a derived mathematical model of the
      process and the characteristics of spatial filters, some conclusions are drawn
      about the way various parameters affect signal quality and continuity.

PMID- 20057537
TI  - Presentation of spectra.

PMID- 20057538
TI  - Two simple cryostats for low temperature fluorescence and absorption
      spectroscopy.

PMID- 20057539
TI  - Convenient mercury source for spectrophotometer alignment.

PMID- 20057540
TI  - Enhancement of photocathode sensitivity by total internal reflection as applied
      to an image tube.

PMID- 20057541
TI  - An image tube design for spectroscopy.

PMID- 20057542
TI  - Modifications in photomultipliers with total internal reflection enhanced
      sensitivity.

PMID- 20057543
TI  - The influence of cathode thickness and aging on the photoelectric yields of LiF
      and CsI in the xuv.

PMID- 20057544
TI  - Geometrical focusing techniques.

PMID- 20057545
TI  - A tunable birefringent Fabry-Perot interferometer.

PMID- 20057546
TI  - Combination laser Q-switch using a spinning mirror and saturable dye.

PMID- 20057547
TI  - ICO-7: the Seventh Congress of the International Commission for Optics.
AB  - The Seventh Congress of the International Commission for Optics was held in Paris
      on 2-7 May 1966. In addition to the business sessions of the congress, attended
      only by official delegates from the 17 member countries, there was an extensive
      scientific conference Recent Progress in Physical Optics. A meeting of members of
      the editorial board of Optica Acta, an international journal of theoretical and
      applied optics, was held during the week. The congress was attended by over 450
      persons, from 20 countries.

PMID- 20057548
TI  - [Optical work in France].
AB  - This paper gives a nonexhaustive review of developments and progress in certain
      fields of optics, concerning itself mainly with the conception and realization of
      instruments. Work in instrumental optics is covered, i.e., photographic and
      astronomical optics, and far uv spectroscopy. Thin film optics. and radio
      frequency, ir, visible, and near uv spectroscopy are not discussed in view of the
      fact that they were surveyed in the previous review of optical work in France
      published in the May 1962 issue of APPLIED OPTICS.

PMID- 20057550
TI  - The use of partially transparent plates to increase the contrast of images.
AB  - Calculations and measurements were made for studying the effect of partially
      transparent plates in order to increase contrast. It was shown that, aside from
      their present use for images on photographic film, these plates may be used for
      increasing the contrast of paper images. The differences in contrast on low
      density areas of images on paper and film may be considerably increased without
      significantly influencing the contrast ratios of high density areas. The increase
      in contrast in all cases results in a loss of the illuminating light energy and
      in some degradation of resolution.

PMID- 20057551
TI  - Optical processing of bubble chamber photographs.
AB  - The processing of bubble chamber photographs has emerged as a major task in the
      experimental study of sub-atomic decays and interactions. Although electronic
      computer techniques have proved useful in reconstructing the geometry and
      ascertaining the kinematics of high-energy events, the scanning and measuring of
      bubble chamber photographs has remained for the most part unautomated. An
      alternate approach to the computerization of the scan-measure task is through the
      newly developed optical computer, a device which accepts input data on
      photographic film and thus obviates the need for digitizing photographs before
      processing. The optical computer can aid the scan-measure task by suppressing
      beam tracks, measuring track widths, and determining scattering angles.

PMID- 20057553
TI  - Spherizing a seven-power, wide-field eyepiece design.
AB  - A seven-power, wide-field, eyepiece design incorporating two paraboloidal
      surfaces was redesigned. The aspherical surfaces presented a manufacturing
      problem that precluded large-scale production of an otherwise satisfactory
      design. The LASL Lens Design Code was utilized to replace the aspherical surfaces
      with spherical ones and to exceed the performance of the original design. The
      improved design has allspherical surfaces, and a report on a prototype eyepiece
      indicates the design to be an excellent one.

PMID- 20057554
TI  - Collisional excitation transfer between the 2P1/2 and 2P3/2 levels in alkali
      atoms.
AB  - An account of recent work is given by the author and co-workers on the
      experimental determination of cross sections for excitation transfer between the
      (2)P((1/2)) and (2)P(3/2)resonance levels in potassium, rubidium and cesium,
      induced by inelastic collisions with alkali atoms and inert gas atoms in their
      ground states. Forty values of cross sections were obtained in a series of
      sensitized fluorescence experiments, in which alkali vapors and vapor-gas
      mixtures were irradiated with one component of the appropriate alkali resonance
      doublet, and the relative intensities of both components appearing in the
      fluorescent light were measured. The experiments indicate that the collisional
      interaction between an alkali atom in a (2)P state and a ground state inert gas
      atom probably occurs between the inert gas atom and the (2)P alkali valence
      electron which behaves like a quasi-free particle.

PMID- 20057555
TI  - Optics from Euclid to Huygens.
AB  - The salient contributions of writers on optics from Euclid to Newton and Huygens
      are outlined, with a workable bibliography, to encourage present-day workers to
      restudy the classical writings and to find ideas that lie outside the paths that
      orthodox optical science has taken.

PMID- 20057556
TI  - Aberration matrices of an axial bundle and an investigation of their elements.
AB  - Two aberration matrices are presented. The first one is the aberrations
      contribution matrix formulated as a difference of two Herzberger refraction
      matrices of an optical surface. The second one is called aberration matrix and
      describes the aberrations of an axial bundle in the Gaussian image plane of an
      optical system. The interpretation of the elements of the aberration matrix is
      given, and the connection of these elements with the spherical aberration and
      Abbe's sine condition is shown.

PMID- 20057557
TI  - Total internal reflection light deflector.
AB  - A digital electrooptic light deflector is described whose deflection elements are
      an isotropic plate and an optically birefringent plate immersed in a refractive
      index matching oil. Total internal reflection or complete transmission takes
      place at the birefringent plate according to the linear polarization state of the
      light beam. The deflector is suited for large deflections and a broad band of
      wavelengths.

PMID- 20057558
TI  - Circular polarization of vacuum ultraviolet light by piezobirefringence.
AB  - An instrument has been constructed that can produce any degree of elliptical
      polarization from linear to circular in the vacuum uv range 1050 A to 1450 A
      using a piezobirefringent retarder of LiF. The apparatus is conveniently
      described by the Mueller matrices. One of the piezobirefringence constants, P(11)
      - P(12), ranged from 4.0-10.0 x 10(-13) cm(2)/dyn for various samples of LiF, and
      the index of refraction at 1216 A was 1.79 +/- 0.14.

PMID- 20057559
TI  - Elimination of microdensitometer degradation from scans of photographic images.
AB  - In microdensitometry, the tracing of a knife edge does not yield a step function.
      Therefore, when a photographic image is traced the result is not a spatially true
      representation of the image. A computational procedure has been developed that
      corrects for microdensitometer effects. This is achieved by obtaining the inverse
      Fourier transform of the reciprocal values of the microdensitometer modulation
      transfer function and convolving the resulting function with the digital output
      of the microdensitometer scan. The result is the corrected scan data for the
      photographic image. This technique has been applied successfully to edge gradient
      analysis for both analytic and experimental edges. The compensation for
      microdensitometer degradation should have a number of applications.

PMID- 20057560
TI  - A photoelectric skylight polarimeter.
AB  - A photoelectric skylight polarimeter to measure directly the Stokes parameters
      for plane polarized light is described. The basic principle of the instrument
      consists in the simultaneous measurement of the intensity of light (in the chosen
      spectral region) transmitted by polarizers oriented in four specific directions.
      The main features and performance characteristics of the instrument are briefly
      discussed.

PMID- 20057561
TI  - Analysis of translucent and opaque photocathodes.
AB  - By an analysis of the photodetection process, the response of photodetectors to
      wide band, noncoherent light and guidelines for its improvement are determined.
      In this paper, the phenomenon of multiple reflections within the emitter of a
      reflecting-translucent and a reflecting-opaque photocathode is analyzed.
      Geometrical and optical configurations and solid state parameters are evaluated
      in terms of their effect on the photodetection process. The quantum yield, the
      percent of incident light absorbed, and the collection efficiency are determined
      as functions of the thickness of the emitting layer. These results are then
      employed to suggest areas of improvement in the use of state-of-the-art
      photocathodes.

PMID- 20057562
TI  - Optimization of preamplifiers for detection of short pulses of light with
      photodiodes.
AB  - The design of the preamplifier used with photodiodes to detect short pulses of
      light is presented. Expressions are derived giving the output signal-to-noise
      ratio in terms of the noise characterization of the amplifier, the
      characteristics of the detector, and its operating conditions. The frequency
      response of a vacuum tube amplifier is specified to give the maximum output
      signal-to-noise ratio. A numerical example is given.

PMID- 20057563
TI  - We can now dispose of some of the opinions.

PMID- 20057564
TI  - Effects of atmospheric turbulence on the transmission of a laser beam at 6328 A.
      I-distribution of intensity.
AB  - The intensity variations of a laser beam by atmospheric turbulence were
      investigated using a He-Ne gas laser at 6328 A with a beam diameter of about 3.5
      mm and optical path lengths of 4.5 km and 14.5 km. The log-normal approximation
      of the intensity distribution was found to be of limited accuracy especially at
      high scintillation. The variation of the scintillation with the diameter of the
      entrance aperture of the photometer (5 mm to 80 mm) was small at the above
      mentioned conditions.

PMID- 20057565
TI  - Applied optics of optics and opticists.

PMID- 20057566
TI  - OSA research and education.

PMID- 20057567
TI  - Effects of atmospheric turbulence on the transmission of a laser beam at 6328 A.
      II-frequency spectra.
AB  - The frequency spectra of light intensity fluctuations of a laser beam by
      atmospheric turbulence were investigated using a He-Ne gas laser at 6328 A with a
      beam diameter of about 3.5 mm and optical path length of L = 4.5 km and 14.5 km.
      The normalized spectra U(f) were not systematically affected by different
      receiving aperture diameters 5 mm <or= D <or= 80 mm, probably because of the
      small diameter of the output aperture of the source. The theoretical relation
      f(c) L(-1/2), where f(c) is a characteristic frequency of U(f), does not appear
      to hold empirically.

PMID- 20057568
TI  - A self-calibrating technique measuring laser beam intensity distributions.
AB  - A technique is described which yields quantitative photographic determinations of
      laser beam intensity distributions. Each photograph is self-calibrated,
      eliminating the effect of variation from one film sample to another, by a
      technique which is indifferent to the nonlinear response of the emulsion. Study
      of the beam divergence characteristics of a saturable dye, Q-switched ruby
      oscillator-amplifier system is presented.

PMID- 20057569
TI  - Underwater transmission characteristics for laser radiation.
AB  - Characteristics of the transmission of visual radiation in water are discussed
      and underwater transmission data applying to extended ranges are presented.
      Measurements have been made with an intense, narrow beam, coherent radiation
      source which has a spectral peak at 5300 A and a bandwidth of 24 A.

PMID- 20057570
TI  - On automatic parallelism control in a scanning Fabry-Perot interferometer.
AB  - A method of keeping the optical plates of a scanning Fabry-Perot interferometer
      parallel when setting on fringe maxima is described. The method needs no
      additional instrumentation other than the duplication of some of the electronic
      detection equipment needed for normal use of the instrument. Small oscillatory
      rotational movements about two axes at right angles are applied to one of the
      interferometer plates, while the other is moving axially in an oscillatory
      fashion. The transmitted light flux from the interferometer is detected with the
      single photodetector, and the electrical signal contains components at different
      frequencies that can be used to measure and control precisely the plate
      separation and plate parallelism of the interferometer. Experiment and analysis
      show that for path differences up to 200 mm using the mercury 198 green line as
      the light source, the parallelism of the plates can be controlled to better than
      10(-8) rad, if parameters in the interferometer system are chosen suitably. For
      path differences up to 100 mm, the accuracy approached 10(-9) rad. With laser
      light, the method should be applicable for long path differences. Vibration and
      medium stability would be the limiting factors.

PMID- 20057571
TI  - Measurement of the spectral emission of infrared radiation of minerals and rocks
      using multiple-scan interferometry.
AB  - The ir spectral emission of a variety of minerals and rocks was measured at a
      specimen temperature of 20 degrees C. A multiple-scan interference spectrometer
      was used. The samples were located within a cold-box during the measurements, the
      experimental arrangement thus simulating the conditions to be found in the field.

PMID- 20057572
TI  - Closed cycle cryogenic refrigerators as integrated cold sources for infrared
      detectors.
AB  - Many ir detectors can only operate when cooled to low temperatures. A short
      description is given of an integrated refrigerator-detector combination in
      airborne use. Experimental results are presented for developmental refrigerators
      in which weight and power input have been reduced to a point where satellite-
      borne operation becomes feasible.

PMID- 20057573
TI  - A heated absorption cell for studying infrared absorption bands.
AB  - A 1-m length absorption cell has been designed for observation of ir absorption
      spectra of gases at high temperatures. The design allows use of windows of NaCl,
      KBr, etc., which have a tendency to cleave when subjected to temperature
      variations. The absorption spectrum of HC1(37)at temperatures in excess of 800
      degrees C revealed more than twenty-five previously unobserved lines in the 1-0
      band of this molecule. Some molecule constants of HCl(37)have been evaluated.
      Usefulness of the cell in work connected with other molecular problems has been
      indicated.

PMID- 20057574
TI  - The operation of a neodymium glass using a saturable liquid Q-switch.

PMID- 20057575
TI  - Stability of an idealized two level laser.

PMID- 20057576
TI  - On the determination of comparator screw errors.

PMID- 20057577
TI  - The Monk-Gillieson mount.

PMID- 20057578
TI  - YVO(4):Eu: a highly efficient, red-emitting phosphor for high pressure mercury
      lamps.

PMID- 20057581
TI  - Hologram on photochromic glass.

PMID- 20057579
TI  - A compact polarizer for the infrared.

PMID- 20057582
TI  - Scanning the issue.

PMID- 20057583
TI  - Crystalline solid lasers.
AB  - A survey of crystalline solid lasers is presented. Crystalline host materials are
      described, pointing out their characteristics pertinent for laser systems. Rare
      earth and transition metal impurities operated as lasers are tabulated and the
      role of sensitization in increasing the overall efficiency of laser systems is
      described. Characteristics of operating CW lasers are given, and some
      applications and research directions are suggested.

PMID- 20057584
TI  - Glass lasers.
AB  - After a general discussion of the merits of glass vs. crystals as host materials
      for laser ions, a summary is given of the various glass lasers. Because of its
      importance as an efficient, room temperature laser the properties of neodymium
      are considered in greater detail. This includes the nonlaser properties of Nd(3+)
      in glass, the spectral and temporal emission characteristics of Nd(3+) lasers,
      and Nd(3+) laser configurations. Separate sections deal with the other two room
      temperature lasers which use Yb(3+) or Er(3+). The problem of thermal stability
      of laser cavities is also discussed. Finally, a survey is given of the glasses
      that are useful as Faraday rotators.

PMID- 20057585
TI  - Gas lasers.
AB  - A review is given of the present status of gas discharge lasers, with particular
      attention to developments reported in 1965 and early 1966. Following a brief
      history, gas lasers are classified by types-neutral atom, ion, and molecular-and
      a comparison is given of the properties of the various types. A short discussion
      is given of noise and coherence properties. Detailed descriptions are given of
      three recent developments of particular interest-the CO(2) laser, the argon-ion
      laser, and pulsed self-terminating lasers. Finally, brief mention is made of the
      most important present applications of gas lasers.

PMID- 20057586
TI  - Semiconductor lasers.
AB  - This paper is a review of semiconductor laser work. The principles of operation
      are discussed. The stress is on work since early 1964. The present state-of-the
      art in GaAs junction lasers is described.

PMID- 20057587
TI  - Pressure shifts in a stabilized single wavelength helium-neon laser.
AB  - Frequency shifts of a 6328 A single frequency laser stabilized on the Lamp dip
      have been measured as a function of total helium-neon pressure and for several
      gas mixtures. The total shift in the pressure region between 2 and 4 torr is
      about 40 MHz, with a constant region between 2 and 2.5 torr. A simplified
      theoretical treatment is given based upon collision broadened phase shifts and
      line widths determined in other laser experiments. It is shown that the
      variations in these parameters with pressure form the basis of an adequate
      prediction of the observed pressure shifts.

PMID- 20057588
TI  - Computer applications of lasers.
AB  - The applicability of lasers to the logic, memory, inputoutput, and data
      transmission linkages portions of computers are analyzed qualitatively. The more
      promising potential applications are considered to lie in the memory,
      interconnection, and input-output areas, and the least promising in the fast
      logic area. Coherent optical data preprocessing is cited as an example of an
      already clearly useful laser application.

PMID- 20057589
TI  - Optical transmission research.
AB  - The availability of coherent sources producing usable amounts of power in the
      optical frequency range has stimulated considerable research in optical
      communications. Devices such as oscillators, modulators, detectors, and ancillary
      apparatus having desirable characteristics exist and are being used to design and
      build prototype terminals. Two possible media are being studied and means are
      being sought to improve their performance. They are 1) through-the atmosphere
      propagation and 2) enclosed media with appropriate focusing and directing
      elements. Experimental optical transmission systems can readily be assembled with
      information capacities in a single RF channel comparable to those of microwave
      radio or millimeter waveguide. Such optical systems are not yet competitive for
      high reliability common carrier service because 1) long-distance transmission
      techniques of adequate reliability have not yet been advanced, and 2) optical
      repeater components are not yet competitive with their lower frequency
      counterparts. Some features characteristic of optical transmission systems are
      reviewed in this paper, along with a brief indication of the state-of-the-art for
      major components.

PMID- 20057590
TI  - Laser beams and resonators.
AB  - This paper is a review of the theory-of laser beams and resonators. It is meant
      to be tutorial in nature and useful in scope. No attempt is made to be exhaustive
      in the treatment. Rather, emphasis is placed on formulations and derivations
      which lead to basic understanding and on results which bear practical
      significance.

PMID- 20057591
TI  - Modes, phase shifts, and losses of flat-roof open resonators.
AB  - The integral Squation of a "flat-roof resonator" is solved by the Fox and Li
      method of iteration in a number of particular cases. Mode patterns, phase shifts,
      and power losses are derived. A good overall agreement is found with the
      approximate theory previously developed by Toraldo di Francia. Some experimental
      tests carried out on a microwave model give a further confirmation of the
      theoretical predictions.

PMID- 20057592
TI  - High-speed photodetectors.
AB  - This paper is intended as a status report on high-speed detectors for the visible
      and near-infrared portion of the optical spectrum. Both vacuum and solid-state
      detectors are discussed, with the emphasis on those devices which can be used as
      direct (noncoherent) detectors of weak optical signals modulated at microwave
      frequencies. The best detectors for this application have internal current gain
      and in this regard the relevant properties and limitations of high-frequency
      secondary emission multiplication in vacuum tube devices and avalanche
      multiplication in p-n junctions are summarized.

PMID- 20057593
TI  - The antenna properties of optical heterodyne receivers.
AB  - An optical heterodyne receiver is, in effect, both a receiver and an antenna. As
      an antenna it has an effective aperture or capture cross section A(R)(Omega) for
      plane wave signals arriving from any direction Omega. The wavefront alignment
      between signal and local-oscillator (LO) beams required for effective optical
      heterodyning may be summarized in the "antenna theorem" integral integral
      A(R)(Omega)dOmega = [eta(2)/eta(2)/lambda(2) where the moments of the quantum
      efficiency eta are evaluated over the photosensitive surface. Thus, an optical
      heterodyne having effective aperture A(R) for signals arriving within a single
      main antenna lobe or field of view of solid angle Omega(R) is limited by the
      constraint A(R)Omega(R) approximately lambda(2). Optical elements placed in the
      signal and/or LO beam paths can vary the trade-off between A(R) and Omega(R) but
      cannot change their product. It is also noted that an optical heterodyne is an
      insensitive detector for thermal radiation, since a thermal source filling the
      receiver's field of view must have a temperature T approximately [In (1+eta )](
      1) hf/k to be detected with S/N approximately 1. Optical heterodyning can be
      useful in practical situations, however, for detecting Doppler shifts in coherent
      light scattered by liquids, gases, or small particles. Another antenna theorem
      applicable to this problem says that in a scattering experiment the received
      power will be less than or approximately Nsigmalambda/4pi times the transmitted
      power, where N is the density of scatterers and sigma is the total scattering
      cross section of a single scatterer. The equality sign is obtained only when a
      single aperture serves as both transmitting and receiving aperture, or when two
      separate apertures are optimally focused at short range onto a common volume.

PMID- 20057594
TI  - Nonlinear optics.
AB  - Recent advances in the field of nonlinear optical phenomena are reviewed with
      particular emphasis placed on such topics as parametric oscillation, self
      focusing and trapping of laser beams, and stimulated Raman, Rayleigh, and
      Brillouin scattering. The optical frequency radiation is treated classically in
      terms of the amplitudes and phases of the electromagnetic fields. The
      interactions of light waves in a material are then formulated in terms of
      Maxwell's equations and the electric dipole approximation. In this method, non
      linear susceptibility tensors are introduced which relate the induced dipole
      moment to a power series expansion in field strengths. The tensor nature and the
      frequency dependence of the nonlinearity coefficients are considered. The various
      experimental observations are described and interpreted in terms of this
      formalism.

PMID- 20057595
TI  - Electrooptic light modulators.
AB  - The field of electrooptic light modulation by means of the Pockels and Kerr
      effects in crystals is summarized with particular attention to communications
      applications using the optical maser. All available data on electrooptic
      materials are tabulated, and design considerations and operating principles for
      various modulator configurations are outlined.

PMID- 20057596
TI  - A review of acoustooptical deflection and modulation devices.
AB  - A review of the principles of acoustooptical devices is given. Some very simple
      momentum conservation considerations indicate the optimum relationship between
      the optical and acoustic beam dimensions for various functions such as scanning
      or modulation. A calculation for the usual type of acoustic amplitude modulation
      is described, and serves as an example of the type of detailed considerations
      that are necessary and possible, as well as a verification of the validity of the
      simple momentum considerations. It is shown that the product of the fraction of
      the light that may be scattered and the bandwidth for Bragg scattering equals a
      materials constant times the acoustic power. This relationship is shown to be
      valid even to the extent of numerical constants for several configurations
      allowing a trade-off between these parameters. Thus, the required modulation
      power for any level of device performance is easily determined. The details of
      acoustic deflection under conditions of acoustic beam focusing or scanning are
      also given.

PMID- 20057597
TI  - Stabilization and modulation of laser oscillators by internal time-varying
      perturbation.
AB  - The paper reviews the application of internal timevarying perturbation to the
      problem of laser mode control and stabilization. The spectral characteristics and
      time domain behavior obtained by means of phase type and loss type perturbations
      are considered. Two techniques which allow the attainment of high single
      frequency output powers from normally multimode lasers are described. A method
      for the absolute frequency stabilization of an FM laser is considered, and a
      brief discussion of an efficient method of internal modulation, termed coupling
      modulation, is given.

PMID- 20057598
TI  - Carbon disulfide traveling-wave Kerr cells.
AB  - Carbon disulfide has identical microwave and optical dielectric constants, as
      well as extremely low optical and microwave loss. These properties make it
      possible to construct long travelingwave light modulators at microwave
      frequencies using the Kerr electrooptic effect induced in CS(2) by an electric
      field propagating on a TEM transmission line.Several experiments with traveling
      wave Kerr cells consisting of resonant strip transmission lines immersed in CS(2)
      are described. A decrease in the microwave power required for modulation by a
      factor of two, by cooling the modulators to a temperature of -55 degrees C, is
      demonstrated. Simultaneous modulation of light at two microwave frequencies by
      excitation of two of the longitudinal modes of the strip line resonator is also
      described. Relatively high efficiency modulation with long devices of this type
      is also reported. In these experiments, the microwave power required for large
      depths of modulation is reduced by almost two orders of magnitude compared to
      previously reported CS(2) light modulators, and is within less than a factor of
      two of the calculated power for cells up to 44 cm in length. For longer cells,
      increasingly larger than predicted powers are required.

PMID- 20057599
TI  - Digital light deflectors.
AB  - Several electrooptic digital light deflection techniques have been proposed. The
      maximum number of resolvable deflection positions for all methods is determined,
      essentially, by economic reasons, the tolerable amount of background light, and
      aberrations. In this paper, three different types of deflection methods (split
      angle, total internal reflection, Wollaston prism) are described. Design,
      construction details, and performance of three deflector models are reported.
      Combined deflection systems use the advantageous properties of each of these
      methods to economically obtain the maximum number of resolvable deflection
      positions. A suggested combination to achieve 1024x1024 positions arranged in a
      two-dimensional field would consist of one total internal reflection stage, seven
      stages of split angles, and two stages of Wollaston prisms for each dimension.

PMID- 20057600
TI  - A television display using acoustic deflection and modulation of coherent light.
AB  - Bragg reflection of laser light by ultrasonic waves in water produces the
      horizontal deflection in a television display. The ultrasonic waves are frequency
      modulated with a sawtooth function. Deflection angles are small but there are 200
      resolvable positions; the constant rate of angular change which characterizes a
      television scan permits the use of a wide optical aperture, leading to a small
      spot size. Conventional optical magnification follows the horizontal deflection,
      rendering a 3 MHz video signal visible on the screen. Bragg reflection requires
      the acoustic wave front to be symmetrical with respect to the incident and
      diffracted light rays. Thus, as the Bragg angle is altered, the acoustic
      wavefront should rotate. This is accomplished by a phased array of transducer
      strips whose combined wavefront rotates as the frequency changes, providing
      excellent correction over a wide band (19 to 35 MHz in this experiment,
      corresponding to a +/-30 percent change in Bragg angle). Broadband electrical and
      acoustical matching techniques make it possible to diffract all the incident
      light with about one watt of electrical input. A second acoustic diffraction cell
      intensity-modulates the light. In an early experiment, the laser beam was
      constricted to a very small diameter before entering the modulator cell; even so,
      the finite beam size caused a significant loss of high-frequency response. An
      improved version uses an old principle (Scophony, 1939): the laser beam
      traversing the cell is made wide enough to encompass several picture elements,
      all traveling across the beam at sound velocity; the horizontal deflection system
      nullifies the apparent motion of these elements making them stand still on the
      screen while a fan of light sweeps over them. With this modulation system,
      spatial coherence is needed only across the vertical dimension of the laser. The
      tolerance on the orientation of the acoustic wavefronts, the improvement brought
      about by the phased array, and the amount of power needed to drive the
      diffraction cell are calculated and the results confirmed by measurement. There
      is also good agreement between the experimentally observed optical resolution
      (spatial frequency response) and the theoretical expectation based on the
      computed far-field intensity pattern.

PMID- 20057602
TI  - A reflection-diffraction microscope for observing diatoms in color.

PMID- 20057601
TI  - A survey of laser beam deflection techniques.
AB  - Methods of high-resolution, high-speed, optical beam deflection and scanning are
      reviewed with respect to resolution and scanning frequency capabilities. A
      general description is given of external deflector devices in the categories of
      variable reflectors, variable refractors, birefringent deflectors, and
      interference deflectors. The different techniques are then evaluated on the basis
      of their application to high-speed, high-resolution, precision scanning
      applications.

PMID- 20057603
TI  - Equations for optical constants suitable for use in a Fortran program.

PMID- 20057604
TI  - Transmittance of components of air for lambda 1850 A.

PMID- 20057605
TI  - Amplitude of Edser-Butler bands in interference filters.

PMID- 20057606
TI  - The measurement of fast current pulses in the kiloampere range.

PMID- 20057607
TI  - Optical activity and electrooptic effect in bismuth germanium oxide
      (Bi(12)GeO(20)).

PMID- 20057608
TI  - Pure relief images on type 649-F plates.

PMID- 20057609
TI  - Stability criteria for one class of tracking horizon sensors.

PMID- 20057610
TI  - Optical activities in the universities.

PMID- 20057611
TI  - Meeting reports.

PMID- 20057612
TI  - Evaluation of absorption and gain from spontaneous emission profiles.

PMID- 20057613
TI  - Quasars.
AB  - A short historical outline of the discovery and a description of observed
      properties of quasars introduces questions as to their nature. Some of the
      principal arguments concerning their reality, distance, intrinsic properties and
      age lead to the conclusion that, while there is room for other points of view; a
      strong case can be made for the interpretation, on which quasars are the most
      distant observable objects in the known universe. To produce such luminosities
      over times of thousands to millions of years requires the presence of millions of
      solar masses. For each quasar this enormous mass may be concentrated into a
      single object, in which case novel physics comes into play. Whatever the final
      interpretation, quasars seem certain to illuminate such questions as the origin
      and evolution of galaxies, perhaps also the structure and origin of the universe.

PMID- 20057614
TI  - Ernst abbe and his work.

PMID- 20057615
TI  - A liquid nitrogen cooled, rocket borne, infrared telescope.
AB  - We have constructed a liquid nitrogen cooled telescope that was flown in an
      Aerobee 150 rocket. The telescope allows measurement of absolute ir signal
      strengths from astronomical objects in the wavelength range out to about 7.5
      micro. In contrast to ground-based telescopes, it can observe diffuse as well as
      discrete astronomical sources.

PMID- 20057616
TI  - Spectropolarimeter for the Infrared (2-8 micro).
AB  - An ir spectropolarimeter for the 2-8-micro region is described. The instrument
      features germanium plate polarizers, double modulation by light chopping and an
      oscillating polarizer, and an optical zero servosystem. The theoretical
      sensitivity of the instrument is derived in some detail, and the results are
      comparedwith the actual sensitivity of 15 mdeg.

PMID- 20057617
TI  - Effective thickness of bulk materials and of thin films for internal reflection
      spectroscopy.
AB  - In internal reflection spectroscopy effective thickness is defined as the
      thickness of material required to give a spectrum of the same contrast in a
      transmission measurement as that obtained via internal reflection. Simple
      expressions for effective thickness are given for bulk materials and for thin
      films which are useful as guide lines in determining the optimum conditions
      required to record internal reflection spectra. Depending on angle of incidence
      and index of refraction, the effective thickness for bulk materials may be much
      greater or much less than the wavelength of light. Similarly for thin films the
      effective thickness may be much greater or much less than the actual thickness.

PMID- 20057618
TI  - OSA research and education.

PMID- 20057619
TI  - Analytical description of a Fabry-Perot photoelectric spectrometer.
AB  - An analytical expression for the response of a complete Fabry-Perot photoelectric
      spectrometer to a line profile is derived. The case of a doppler-broadened
      Lorentzian profile examined by a spectrometer comprised of an etalon of variable
      thickness and reflectivity, with surface defects consisting of spherical
      curvature, as well as microscopic flatness imperfections, a finite exploring slit
      in front of the photodetector, and bandwidth limiting circuits is considered.
      Some of the properties and uses of the expression obtained are discussed.

PMID- 20057620
TI  - Angular dependence of transmission characteristics of interference filters and
      application to a tunable fluorometer.
AB  - The technique of tilting the Fabry-Perot type interference filters for the
      purpose of producing continuous displacements in their passband positions was
      investigated. The optical properties of interference filters with semitransparent
      silver films are discussed from the theoretical standpoint. The results are then
      compared with experiment. Based on the tilting technique, an interference filter
      fluorometer is proposed that is designed to obtain a variety of spectroscopic
      data under the experimentally adverse conditions of weak excitation and
      fluorescence.

PMID- 20057621
TI  - The stability of interference filters.
AB  - Visible interference filters were subjected to a large range of thermal
      conditions during and after manufacture. The positions of the passbands were then
      monitored at intervals for up to one year. It is suggested that crystal growth in
      the spacing layer explains most of the passband changes that were observed. Some
      practical applications of this work are indicated.

PMID- 20057622
TI  - Practical considerations for the use of spatial carrier-frequency filters.
AB  - The article discusses several practical problems in the use of spatial carrier
      frequency filters in coherent optical systems, and describes an interferometric
      system that offers many practical advantages in constructing such filters. Also
      described is an optical configuration that can easily search for the scale of a
      signal, as well as its location and orientation. The use of a prism in the
      optical configuration simplifies the search for the orientation and scale of the
      signal. The spatial carrier-frequency filter introduces some aberrations, but
      only astigmatism and distortion remain uncorrected. The necessary magnitude of
      the spatial carrier frequency depends upon the size of the signal and of the
      input data. A natural extension of this consideration leads directly to a
      corresponding requirement on the spatial carrier frequencies for multiplexed
      filters.

PMID- 20057623
TI  - The elimination of building vibration in an optical laboratory.
AB  - The elimination of vibration is a straightforward engineering job that is
      analogous to the design of an electrical filter. The building vibration, which
      was so intense that no serious interferometry was possible, was measured using a
      commercial vibration meter. A simple, single-mesh mechanical filter was designed
      to remove the existing frequencies of vibration. The filter was constructed and
      its performance measured. As a practical test of the performance of the vibration
      elimination, a hologram was made on the vibration isolated granite slab.

PMID- 20057624
TI  - Aerosol measurements in the troposphere and stratosphere.
AB  - Light scattering measurements from a searchlight beam were carried out in New
      Mexico to determine the aerosol properties of the atmosphere. Although data were
      acquired to an altitude of about 70 km, the results show the aerosol attenuation
      parameters to be significant to about 35 km. The expression for the aerosol
      attenuation coefficient is derived based on the field geometry in conjunction
      with Rayleigh and aerosol scattering considerations. The results are categorized
      into moderate-structured, medium-structured and full-structured aerosol profiles.
      Examples of each are discussed and measurements presented which show variation
      over a 6-h period. A quantitative examination is made of the 20-km aerosol layer.
      Also, a medium-structured profile is selected and treated more extensively to
      provide preliminary information pertaining to atmospheric scattering and
      transmission. Ultimately, the data accumulated will provide a substantial number
      of profiles that will form a basis for various atmospheric studies.

PMID- 20057625
TI  - Biased resonance circuits for electrooptic digital deflectors.
AB  - A number of circuits for electrooptic digital deflectors is presented. These
      circuits minimize power dissipation by utilizing the novel technique called
      biased resonance. This technique is based on the coincidence of zero points of a
      raised cosine and its derivative. Test results are reported for one circuit that
      operated at 2200 V, with a load capacitance of 200 pF, and at greater than 100 k
      baud rate. Dissipation for this breadboard model was 10 W. Other circuits are
      shown; their advantages and disadvantages are discussed. Also discussed are some
      future switching device requirements.

PMID- 20057627
TI  - The format of the AIP Style Manual.

PMID- 20057626
TI  - Optical spectrum analysis of large space bandwidth signals.
AB  - Coherent optical spectrum analyzers are available for determining the frequency
      content of many analog signals written simultaneously on film. The space
      bandwidth product of each signal must not exceed one thousand for a typical 35 mm
      system. By sacrificing the multichannel capability of such a computer, single
      signals with space bandwidth products greater than one million (10(6)) can be
      analyzed. Two optical systems are described. The first analyzes long signals but
      maintains the frequency resolution of the multichannel system (one part in one
      thousand). The second system yields frequency resolution of at least one part in
      one million. Near real-time, continuous spectrum analysis of analog signals is
      within the current state of the art. A breadboard system is being built.

PMID- 20057628
TI  - Use of the Curtis-Godson approximation in calculations of radiant heating by
      inhomogeneous hot gases.
AB  - Calculations of radiant heating by inhomogeneous hot gases require knowledge of
      spectral transmittances of inhomogeneous optical paths. Determination of these
      transmittances is a difficult problem that can be attacked by means of the Curtis
      Godson approximation, which replaces each inhomogeneous optical path with a
      hypothetical homogeneous path that has the same transmittance. The authors have
      tested the accuracy of the Curtis-Godson approximation experimentally. Infrared
      spectral transmittances of inhomogeneous hot samples of H(2)O and CO(2) were
      measured. Each inhomogeneous hot gas specimen consisted of two or three
      homogeneous zones in series. The transmittance of each zone was measured, as was
      the transmittance of the entire multizone assembly. The measured transmittance of
      each inhomogeneous path was compared with a transmittance calculated from the
      homogeneous zonal transmittances, using the Curtis-Godson approximation in
      conjunction with a random band model. The measured and calculate inhomogeneous
      transmittances concurred to within about 0.02. The error appeared to be due more
      to the band model theory than to the Curtis-Godson approximation.

PMID- 20057629
TI  - Band models for nonisothermal radiating gases.
AB  - Approximate relations are presented for calculating the mean spectral
      distribution of the net radiance at the boundary of a nonisothermal gas, given
      the distributions of temperature, pressure, and composition within the region and
      the appropriate experimental spectral absorptance data. Experimental data
      obtained for the 2.7-micro bands of H(2)O, in which variations in temperature
      between 900 degrees K to 1200 degrees K were imposed along a 60-cm path at
      various pressures, are compared with calculations based on a strongline model. A
      more general band model expression is proposed for intermediate optical depths.

PMID- 20057630
TI  - The determination of image irradiance in optical systems.
AB  - The irradiance produced at image points in any lossless optical system by an
      extended diffuse radiator of given radiant emittance is determined by the final
      pencil of rays and the indices of refraction of object and image space, and can
      easily be calculated using thermodynamic reciprocity. Graphs and formulas are
      given to show the degree to which parabolic and spherical reflectors depart from
      the usual paraxial irradiance formulas when an extended source or a small source
      is placed near the aperture. An expression is derived for the off-axis irradiance
      in systems having circular symmetry and no vignetting.

PMID- 20057631
TI  - The calibration of scanning monochromators for the measurement of absolute
      irradiance.
AB  - Certain approximations commonly used in the absolute calibration of a scanning
      monochromator are examined in terms of the response of the instrument to a
      monochromatic input. The absolute irradiance due to any spectral feature in the
      neighborhood of lambda(0) is commonly computed from the expression W =
      AB(lambda(0))/H(lambda(0)) where A is the area of the spectral feature as
      recorded by the monochromator output trace, B(lambda) is the spectral irradiance
      of a standard source, and H(lambda) is the response of the monochromator to
      B(lambda) when the monochromator corresponds to wavelength lambda. As an example,
      approximations used in justifying such calculations are examined and applied to
      an Ebert 0.5-m monochromator. For the case chosen, the approximation is shown to
      be valid to an accuracy of 1.5% to 2%, depending upon assumptions made in the
      calculation. It is found that the most serious error for this example is
      introduced by changes in the sensitivity of the monochromator over a wavelength
      interval comparable with that of the spectral feature under investigation. A
      second source of error is found to be the change in the irradiance of the
      standard source over a wavelength interval comparable to the instrument resolving
      power.

PMID- 20057632
TI  - Nonlinear effects produced by Raman maser radiations.
AB  - A systematic study was made of the second harmonic generations and the mixings of
      the Raman lines produced in cyclohexane, acetone, benzene, and carbon disulfide.
      In our experimental setup, the Raman cell was placed outside the optical cavity.
      The second harmonic of the first-order Stokes radiation was directly
      photographed. In the case of cyclohexane, the diameter of the focused second
      harmonic corresponded to an angular spread of about 2 or 3 x 10(-2) rad. The
      power produced in the SHG was more than 1 kW. The spectrographic study shows that
      the SHG and the mixings of various Raman lines are efficient. Their details are
      outlined in the case of individual liquids. In terms of cyclohexane, the SHG and
      the mixings of Raman emissions produced from the other molecular vibration (801
      cm(-1)) are also observed. The reported observations indicate that the Stokes
      lines, beyond first order, produced in a forward direction with a threshold
      condition, are strong enough to show these nonlinear effects.

PMID- 20057633
TI  - Characteristics of a lambda/2 Kerr cell ruby oscillator for use as an optical
      radar (Lidar).
AB  - A Q-switched ruby laser has been developed that is useful as an optical radar for
      clear air turbulence detection. The output is a single clean pulse of 35 MW, free
      of noise sources such as spontaneous emission, superradiance, and after-pulsing.
      A comparison is made with the standard quarter-wave mode of operation.

PMID- 20057634
TI  - Velocity aberration and atmospheric refraction in satellite laser communication
      experiments.
AB  - The effects of satellite velocity aberration and atmospheric refraction on the
      direction of propagation of lagser radiation reflected from a satellite back to
      an observer on the earth are examined. A velocity aberration analysis for the two
      dimensional case where the satellite passes directly overhead at velocity v is
      presented to first order in v/c in order to illustrate the method. The equations
      for the more general threedimensional case are then given to first order in v/c,
      and it is indicated that higher order treatments are normally unnecessary in
      typical experimental considerations. Following this, a simple approximate
      equation giving the atmospheric refraction to an accuracy of a few microradians
      is developed; it is indicated that greater accuracy is not important because of
      laser pointing limitations imposed by atmospheric scattering and turbulence. The
      atmospheric refraction equation depends only on the apparent zenith angle of the
      satellite reflector relative to the earth-based laser, on the satelli-te
      altitude, and on the index of refraction of the laser radiation in the atmosphere
      at the earth's surface. Both of these developments should be useful in the design
      and interpretation of satellite laser-communication experiments.

PMID- 20057635
TI  - The effect of the earth's radiation belts on an optical system.
AB  - A photoelectric optical imaging system has survived one year in the earth's
      radiation belts with no measurable (<20%) change in sensitivity. The system
      passes through all of the radiation belts twice every 64 hr, and experiences a
      noise level equivalent to 400 photons/sec when in their most intense regions.
      While this noise is far less than that of other photoelectric systems operating
      in the belts because of the small effective area of the photocathode, the noise
      per unit cathode area is 1.3 x 10(5) photons/sec-cm(2), and is similar to the
      best of the other systems. The number and energy distribution of incident
      particles is calculated and then combined with shielding estimates to give the
      total energy absorbed in the optical elements. Radiation damage reports in the
      literature are shown to be consistent with the lack of a sensitivity change in
      this orbiting optical system. The effects of particle radiation on optical
      systems in general is briefly summarized, with emphasis on recent work of others.

PMID- 20057636
TI  - Optimization of optical systems.
AB  - The power signal-to-noise ratios for coherent and noncoherent optical detection
      are presented, with the expression for noncoherent detection being examined in
      detail. It is found that for the long range optical system to compete with its
      microwave counterpart it is necessary to optimize the optical system. The optical
      system may be optimized by using coherent detection, or noncoherent detection if
      the signal is the dominate noise factor. A design procedure is presented which,
      in principle, always allows one to obtain signal shot-noise limited operation
      with noncoherent detection if pulsed operation is used. The technique should make
      reasonable extremely long range, high data rate systems of relatively simple
      design.

PMID- 20057637
TI  - Wide angle lenses with aspheric correcting surfaces.
AB  - Refracting elements having aspheric correcting surfaces near the center of
      curvature are analyzed. As in the case of the Schmidt reflector, such systems can
      have a wide aperture and a wide field of view; in addition, they are free from
      obstructing surfaces. Being uncorrected for dispersion, however, the refracting
      systems are restricted to nearly monochromatic radiation. Typical forms of the
      correcting surfaces have been determined, both by third-order theory and by
      numerical integration of exact equations.

PMID- 20057639
TI  - A functioning model of the Soft X-ray slitless spectrometer.

PMID- 20057638
TI  - The effect of a sinusoidal wavefront on the transfer function of a circular
      aperture.
AB  - The influence of a radially symmetric sinusoidal aberration function on the
      behavior of the transfer function is studied. It is shown that the main effect of
      the sinusoidal wavefront is manifest in the low frequency region of the transfer
      function with a rapid drop in contrast. The transfer function is computed via the
      sampling theorem for some typical situations. Finally, it is shown that when the
      wavefront is crinkly there is no coupling between the superposed wavefront and
      the wavefront owing to the natural aberrations of the optical system.

PMID- 20057640
TI  - The effect of strong RF fields on an infrared spectrometer.

PMID- 20057641
TI  - Calculation of the noise equivalent temperature of a radiometer.

PMID- 20057642
TI  - Radiance temperature at 6550 a of the graphite arc.

PMID- 20057643
TI  - Comments on a note by Moser, Steffen, and Kneubuhl.

PMID- 20057644
TI  - Adapting the Jarrell-Ash model 75 spectrograph for time-resolved spectroscopy.

PMID- 20057645
TI  - A method for the production of far infrared transmission filter gratings.

PMID- 20057646
TI  - Materials for optical instrumentation.

PMID- 20057647
TI  - Thermal expansion and other physical properties of the newer infrared
      transmitting optical materials.
AB  - Values are given of the linear coefficient of thermal expansion for several of
      the newer ir-transmitting optical materials, as determined in the authors'
      laboratory. The materials include the six Irtrans (hot-pressed compacts), T-12,
      three single-crystal materials (magnesium fluoride, silver bromide, and cadmium
      fluoride), and two nonoxide glasses. Additional physical properties of these
      materials and of some of the older ir-transmitting materials are given in a large
      table for purposes of ready reference and comparison.

PMID- 20057648
TI  - Nonoxide chalcogenide glasses as infrared optical materials.
AB  - In recent years, glassy systems based on the group VI A elements S, Se, or Te in
      combination with group IV A and group V A elements or V A elements alone, have
      been investigated as potential sources for new iroptical materials. The results
      obtained in the qualitative evaluation of glasses from many systems reported in
      the literature are given. Several specific compositions from different glass
      systems have been prepared in amounts large enough to allow quantitative
      evaluation of optical and related physical properties. The magnitudes of the
      parameters that describe the properties of chalcogenide glasses are discussed and
      compared to those of other ir optical materials. The methods currently used to
      compound the glass compositions are given and problems associated with
      fabrication are briefly discussed. Three potential sources of limited quantities
      of chalcogenide glasses are given.

PMID- 20057650
TI  - Considerations in the use of beryllium for mirrors.
AB  - Some practical problems associated with the use of beryllium as a mirror
      substrate material are analyzed, with particular emphasis on nonelastic strains
      that may affect mirror performance. Present information on the nonelastic
      behavior of beryllium is summarized.

PMID- 20057651
TI  - Relation between refractive index and density of glasses resulting from annealing
      compared with corresponding relation resulting from compression.
AB  - The change in refractive index and associated change in density of glasses on
      annealing has been determined by Tool, Tilton, and Saunders. The corresponding
      changes for the same glasses, produced by hydrostatic compression are presented
      here and compared with those of Tool et al. It is found that, for a given
      increase in density on annealing, the increase in index is greater than for the
      same measured increase in density on compression. The results are interpreted in
      terms of equations developed by Lorentz-Lorenz, Pockels, and Mueller to show,
      first, that in all cases, whether from annealing or compression, there is a
      decrease in polarizability and an increase in density (these results are in
      agreement with those of previous investigators) and, second, that the decrease in
      polarizability for a given increase in density is greater on compression than on
      annealing.

PMID- 20057653
TI  - Partial dispersion ratios of some new borate and phosphate glasses.
AB  - The partial dispersion ratios of phosphate and borate glasses are defined and
      found significantly different from those of silicate glasses; thus, they are
      useful for secondary spectrum correction. Refractive index measurement accuracy
      necessary to ensure significant partial dispersion ratios is analyzed.
      Measurement techniques and corrections are described.

PMID- 20057655
TI  - the optics community.

PMID- 20057654
TI  - Optical characteristics of a proposed reflectance standard.
AB  - The results of optical studies on ceramic fibers indicate that this material may
      be a good reflectance standard and coating material for integrating spheres. It
      is highly reflective in the ir from 1.8 micro to 6.0 micro, and reasonably so at
      wavelengths as short as 0.25 micro. Other attractive features about this material
      are its stability and its availability in virtually any size. Spectral
      reflectance and goniometric reflectance curves are presented, and a calculation
      is given that shows the improvement in efficiency when the material is used in an
      integrating sphere the size of that in the Beckman DK-2 spectroreflectometer.

PMID- 20057656
TI  - Measurements of infrared fluorescence of certain optical materials as stimulated
      by visible light.
AB  - Some ir transmitting materials fluoresce in the near ir spectral region when they
      are stimulated by visible light. An investigation of twenty-three different
      optical materials that might be used as elements in ir samples revealed that
      thirteen of these materials fluoresced to some degree. Quantitative measurements
      of the fluorescence were made by irradiating disks of the materials on one side
      with 0.2-W of visible light and measuring the radiance of the other side.
      Spectral measurements of the fluorescence of some of the samples were also made
      by use of bandpass interference filters. This fluorescence is of interest in
      instances where it might diminish the image contrast in instruments or adversely
      influence calibration.

PMID- 20057657
TI  - Growth problems of sapphire and ruby of optical quality.
AB  - A careful analysis of the basic mechanisms of the Verneuil process led to a
      methodical study of the many parameters associated with it. Among these, the feed
      rate, retraction rate, and flame characteristics were found to be most important.
      A photoelectric cell as the sensor for a servo system with two outputs was used
      to sense the plane of crystallization and control its position. A completely
      automated Verneuil apparatus, incorporating this and other control systems,
      suitable for the study of growth under well-defined, rigidly controlled, and
      dependably reproducible conditions was designed and constructed.

PMID- 20057658
TI  - Stress induced defects in vitreous calcium aluminates.
AB  - Induced flaws on vitreous calcium aluminates were investigated quantitatively by
      applying controlled loading forces to fresh breakage surfaces. Test surfaces were
      chemically treated to display surface flaws, dynamically created by an indenter.
      The mean value of flaw length was linearly related to the square root of the
      applied load on the indenter. A critical stress of flaw formation was calculated
      from the experimental data. Introduction of silica as a dopant and vacuum melting
      conditions were found to influence flaw length. Silica weakened the structure and
      produced a lower critical stress of flaw formation, whereas vacuum melting
      resulted in an increase in this value. An influence of internal defect
      concentration was also indicated by variations in the ir transmission
      characteristics of the glasses. The indicated OH(-) screening effects at 2.8
      micro were in agreement with the findings from the flaw studies. A defect array
      on fresh breakage surfaces suggested the formation of vacancies, and within this
      pattern the indenter forces produced an interesting localized displacement
      effect. The magnitude of the displacement agreed with a proposed vacancy
      diffusion mechanism.

PMID- 20057659
TI  - Infrared spectral emittance measurements of optical materials.
AB  - Optical properties of solids are usually determined by measurements of either the
      transmittance or the reflectance. Each of these methods has advantages and
      disadvantages, depending upon the spectral region and the nature of the material
      being studied. A third method, the measurement of emittance, although little used
      has definite advantages under certain conditions.

PMID- 20057660
TI  - Solid organic filters for 2000 A to 3000 A.
AB  - Earlier work on the development of organic, narrow bandpass solution filters with
      transmittance maxima in the 2000-3000-A range is extended to the fabrication of
      solid filters using a polymethyl siloxane resin as the host material. Three
      transmission filters are described having maxima at 2250 A, 2265 A, and 2840 A,
      respectively, with bandwidths <or=225 A. Transmittance and spectral response
      curves with CsTe photocathodes are given. Results of environmental tests show
      that these filters are well suited for balloon and space missions.

PMID- 20057661
TI  - Interferometric observations of yield in thallium bromo-iodide.
AB  - Plastic flow has been determined quantitatively in a thallium-bromo-iodide (KRS
      5) crystal as a function of applied force and loading time. A
      microinterferometric technique was employed to examine the depth and contours of
      depressions formed by statically loaded steel spheres and the elastic recovery of
      the material. An unusual geometric pattern was formed around a small percentage
      of the load regions, the nature of which suggested slip line formation in the
      cubic crystal lattice.

PMID- 20057662
TI  - Further remarks on electron beam pumping of laser materials.
AB  - This article demonstrates that recently completed studies on the energy
      dissipation of kilovolt electron beams in solids provide readily applicable
      methods for assessing the situation in electron beam pumped lasers.

PMID- 20057663
TI  - The detectivity of intensifier image tubes.
AB  - A theoretical development has been applied to intensifier image tubes which is
      similar to that used for ir photodetectors. In essence, a differential equation
      applicable to intensifier image tubes has been used to obtain exact solutions for
      signal and noise. These expressions account for factors such as phosphor time
      constant, area, frequency response, resolution, and efficiency. They can be
      inserted into the definitions of Noise Equivalent Power, Detectivity Star, and
      Detective Quantum Efficiency to provide exact expressions indicating the
      dependence of these quantities on basic factors governing tube operation and
      performance. An experimental arrangement is described to measure the light signal
      and noise from the intensifier, utilizing a traveling test wave rather than a
      stationary TV type of test pattern. This permits image tube evaluation on the
      same basis as photodetectors.

PMID- 20057664
TI  - Accuracy and sensitivity of the thermal lens method for measuring absorption.
AB  - The effect of two lenses inserted in an optical resonator is studied. The
      modified resonance condition is given together with the stability condition and
      the spot sizes at the mirrors. Diagrams are given which allow the focal lengths
      of two lenses to be calculated from the known spot sizes at both mirrors. The
      effect of a third (the thermal) lens is studied and conditions for calculating
      its focal length by measuring the spot size at one mirror only are examined. The
      experimental procedure for the measurement of absorbencies by the thermal lens
      method is outlined. The various effects that can affect the precision of the
      measurement are studied, and the conditions for maximum sensitivity of the method
      are given.

PMID- 20057665
TI  - Destructive readout in image tubes.
AB  - In conventional analyses of the readout process in image tubes, the scanning
      electron beam is described by means of a passive aperture function. Since the
      generation of an output signal depends upon neutralization of stored positive
      charge elements by the electron beam, it is clear that the beam's action is not
      passive. A progressive diminution or erasure of the stored charge density
      accompanies the progress of the electron beam. In this paper, a simple linearized
      model of the readout process is developed which incorporates progressive erasure
      of the stored image. Sample calculations are presented for the case of point
      targets. The analysis discloses three principal effects of image erasure: (1) the
      output signal corresponding to a point target appears on several successive
      raster lines with an asymmetric variation in strength; (2) the output signal
      derived from a symmetric charge pattern on the storage target is asymmetric in
      time along a single raster line; (3) the output signal reaches its maximum value
      before the center of the electron beam reaches the peak of the stored charge
      pattern.

PMID- 20057666
TI  - Copying holograms.
AB  - A technique for producing many copies from one hologram is presented. This method
      involves using either the real or the virtual image (or both) reconstructed by a
      hologram as an object for a second hologram, with the undiffracted or zero-order
      wavefront being used as the reference beam. Such a procedure allows duplicating
      the first hologram without requiring close contact between the two emulsions
      involved. As in the recording of original holograms, a laser is used for the
      copying described.

PMID- 20057667
TI  - Lens design for a 609.6-mm, f/6, 30 degrees -field objective.
AB  - As a test problem, an attempt was made to optimize a Heliar aerial photography
      lens already designed for optimum performance by classical methods. Improved
      performance was obtained in off-axis image resolution and contrast. Evaluations
      of both lens designs are given, together with the modifications prescribed as a
      result of machine analysis with the LASL program, which analyzes statistically
      the traced skew rays generating the geometrical image spots.

PMID- 20057668
TI  - A cost-aperture study of a family of lenses.
AB  - A series of five lenses ranging in aperture from f/1.0 to f/1.6 were designed
      with the aid of a large computer. A search was made for the least complex lens
      that would yield a given level of optical performance in an effort to optimize
      manufacturing costs with relation to lens speed for a family of lenses. Such a
      relationship was established.

PMID- 20057669
TI  - A preliminary investigation of the bidirectional spectral reflectance of V
      grooved surfaces.
AB  - The bidirectional spectral reflectance of a set of V-grooved surfaces has been
      investigated in an attempt to separate the influences of the mean slope and the
      peak-to-valley height. The experimental results show good agreement with the
      theoretical models in both the geometrical optics and diffraction ranges.

PMID- 20057670
TI  - Polishing of CsI windows for use in the infrared.

PMID- 20057671
TI  - A new radiometric equation and its application.

PMID- 20057672
TI  - CO(2) laser self-modulation characteristics.

PMID- 20057673
TI  - Photoelectric detection of displacement from focus.

PMID- 20057674
TI  - A note on the surface accuracy and alignment of the end mirrors in a Michelson
      interferometer.

PMID- 20057676
TI  - Optical system for a universal luminance meter.

PMID- 20057675
TI  - Complicated smear camera slits.

PMID- 20057677
TI  - The near ultraviolet optical constants of lanthanum fluoride.

PMID- 20057678
TI  - An improved design for vacuum ultraviolet resonance lamps.

PMID- 20057680
TI  - A comment on the scattering of coherent light.

PMID- 20057679
TI  - A note on high resolution spectroscopy in the far infrared.

PMID- 20057681
TI  - Holograms and spatial filters processed and copied in position.

PMID- 20057682
TI  - Diffraction patterns of alphanumeric characters.

PMID- 20057683
TI  - On the wavelength dependence of the spectrum of laser beams traversing the
      atmosphere.

PMID- 20057684
TI  - Beat-frequency interferometer with moving mirror.

PMID- 20057685
TI  - The early history of optics at the National Bureau of Standards.
AB  - The early history of the establishment of the National Bureau of Standards and of
      its work in optics is surveyed, as evidenced by its publications appearing in the
      period 1901-1925.

PMID- 20057686
TI  - Measures for Progress--a history of the National Bureau of Standards, by Rexmond
      C. Cochrane. Editorial consultant, James R. Newman. With a foreword by Vannevar
      Bush and a preface by Allen V. Astin. 703 pp. Published by the National Bureau of
      Standards, U.S. Department of Commerce. 1966.

PMID- 20057687
TI  - Physiological optics at the national bureau of standards.
AB  - Published work in physiological optics at the National Bureau of Standards is
      summarized under the headings: evaluation of light-dark patterns, light
      measurements, color measurement, color differences, and color perception. The
      bearing of this work on standard methods of the American Society of Testing and
      Materials, of the Illuminating Engineering Society, and of the American Standards
      Association, and on recommendations of the International Commission on
      Illumination is indicated. The purposes and methods of current work are briefly
      described.

PMID- 20057688
TI  - Applied optics of optics and opticists.

PMID- 20057689
TI  - Photographic standardization and research at the national bureau of standards.
AB  - The Image Optics and Photography Section of the National Bureau of Standards
      provides physical standards of measurement and calibration services, cooperates
      with national and international standardizing organizations, and conducts
      research related directly to the utilization of photographic materials and
      processes. Standardization and research in sensitometry, standard light sources,
      emulsion making, preservation of photographs, precise densitometry, and image
      evaluation have spanned a half century.

PMID- 20057690
TI  - Instrumental aspects of synchrotron XUV spectroscopy.
AB  - Electron synchrotrons are becoming increasingly important as sources of extreme
      uv radiation for physical experiments. The NBS 180-MeV machine has been utilized
      for gas absorption studies over a four-year period, during which a 3-m grazing
      incidence spectrograph and monochromator have been designed, constructed and put
      into operation. The instruments are extremely stable to vibration and temperature
      variation, and are operating with a slit limited resolution of the order of 0.06
      A. The design principles and features of these instruments are described, and a
      highly successful prealignment procedure for grazing incidence spectrometers is
      outlined. The effect of the unusual characteristics of this light source on the
      illumination and performance of the spectroscopic instruments is discussed.

PMID- 20057691
TI  - Molecular emission spectra in the soft X-ray region.
AB  - Spectra from several chlorine-containing hydrocarbon molecules excited to x-ray
      fluorescence have been recorded by a double crystal spectrometer with high
      resolving power. This study focuses on the region near the occurrence of the
      transition Kbeta(1,3) (1s(-1)-->3p(-1)) in chlorine. Whereas the free atom
      spectrum (from a single vacancy process) consists of an unresolved spin-orbit
      doublet, e.g., in argon, the molecular spectra often contain several lines. In
      free atom spectra and in molecular spectra also, there are extra lines or
      unresolved multiplets (satellites) due to multiple vacancy processes. In this
      report, these satellite lines are experimentally sorted out of the spectra and
      the remaining emission peaks associated with possible final state configuration
      containing a vacancy, i.e., the electronic terms of the molecule.

PMID- 20057692
TI  - Newly measured and calculated wavelengths in the vacuum ultraviolet spectrum of
      neutral nitrogen.
AB  - The NBS 10.7-m vacuum spectrograph was used in the second order to obtain
      precision measurements of three N I lines at 1492-1495 A (2p(3)(2)D degrees 
      2p(2)3s(2)P) and four at 1742-1745 A (2p(3)(2)P degrees -2p(2) 3(s)(2)P). By
      combining these values with other available information on the energy levels of
      the neutral nitrogen atom, seventy-eight calculated wavelengths of N I from 908 A
      to 1745 A are given with uncertainties of 0.001 A or less.

PMID- 20057693
TI  - A vacuum ultraviolet flash photolysis apparatus.
AB  - An improved apparatus for performing vacuum uv flash photolysis-kinetic
      spectroscopy has been constructed. The deviceconsists of a compact coaxial
      arrangement of six capacitors and six electrode pairs symmetrically placed about
      a hexagonal reaction vessel of large aperture. The reaction vessel contains LiF
      windows to transmit far uv radiation. The six pairs of electrodes and six
      capacitors are connected separately and are synchronously fired, uniformly
      illuminating the reaction cell. The photolytic light pulse duration is about 5
      microsec. More than 10(18) quanta enter the reaction vessel in the spectral
      region between 1050 A and 1600 A. The essential operating features of the
      apparatus are described.

PMID- 20057694
TI  - Optical activtes in the universities.

PMID- 20057695
TI  - Optical refractive index of air: dependence on pressure, temperature and
      composition.
AB  - The theoretical background and present status of formulas for the refractive
      index of air are reviewed. In supplement to Edlen's recently revised formula for
      relative refractivity, the density dependence of refractive index is reanalyzed.
      New formulas are presented for both phase and group refractive index which are
      more useful over a wide range of pressure, temperature, and composition than any
      presently available. The application of the new formulas to optical distance
      measuring is briefly discussed.

PMID- 20057696
TI  - Optical constants of germanium.
AB  - The authors have attempted to assess the disagreement of various investigators on
      the optical properties of germanium in the far uv. The analyis subjected the
      reported data, out to about 25 eV, to the following tests: (1) an internal
      consistency check when possible by applying the Kronig-Kramers dispersion
      relations to the optical constants; (2) an evaluation of the optical oscillator
      strength distribution for the spectrum under study; (3) correlation of the values
      of Im(l/*) from the optical data with the characteristic electron energy loss
      spectrum for the material; and (4) evaluation of the oscillator strength sum for
      the electron energy loss distribution. A set of optical constants derived from
      the characteristic electron energy loss data is presented and discussed. Also, an
      estimate of the source of errors incurred in the application of the Kronig
      Kramers dispersion relations are given and discussed in terms of optical data.

PMID- 20057697
TI  - Measurements on the molecular nitrogen pulsed laser.
AB  - Accurate wavelength measurements of the pulsed laser emission from the nitrogen
      molecule have been made. About one hundred new stimulated emission lines which
      belong to the first and second positive systems were obtained and identified as
      to rotational quantum number. The relative intensities of the laser lines in the
      rotational band spectrum are analyzed. Some characteristics of the oscillations,
      including the recovery time after the laser pulse, are discussed.

PMID- 20057698
TI  - Laser probe excitation in spectrochemical analysis.I: characteristics of the
      source.
AB  - A modified laser probe for spectrochemical analysis is described. A high energy
      laser beam is focused onto a specimen to vaporize a sample from a small area, and
      the vapor thus formed is further excited by a spark discharge. The
      characteristics of emission spectra with and without auxiliary spark excitation
      are compared. Spectrograph illuminating systems for qualitative and quantitative
      analysis were investigated. Some difficulties were encountered with the laser
      probe, and modifications were made to the instrument to alleviate some of these
      problems. Some typical analytical applications are discussed.

PMID- 20057699
TI  - Laser probe excitation in spectrochemical analysis. II: investigation of
      quantitative aspects.
AB  - A study has been made of quantitative analysis by a laser probe with spark
      excitation of the sample vapor. Random errors come largely from variations in
      laser energy and from photometric errors. The parameters of the spark circuit
      affect the line intensities; however, these factors are well controlled.
      Correlations have been established between the energy of the laser beam, the size
      of the pit formed, and spectral intensities. For most purposes, single-spike
      laser operation has been found to be preferable to multiple-spike operation. At
      present, the coefficients of variation for analysis are 15% to 40%.

PMID- 20057700
TI  - Spectral radiance of a low current graphite arc.
AB  - The spectral radiance of the anode of a low current graphite arc has been
      determined throughout most of the 850-210 nm region by utilizing a recently
      developed high accuracy spectroradiometer. The estimated standard deviation
      uncertainty varies from about 1.5% at the longer wavelengths to about 5% at the
      shorter. Results are given at twenty wavelength points in the region and also as
      a continuous function of wavelength throughout most of the region, excluding some
      areas of high molecular band radiation originating in the arc stream.

PMID- 20057701
TI  - The new tungsten-filament lamp standards of total irradiance.
AB  - The National Bureau of Standards standard of total irradiance as presently issued
      in the form of a 50-W carbon filament lamp was originally calibrated more than
      fifty years ago. Recently, needs for higher accuracy and wider ranges of total
      irradiance have necessitated the setting up of three sizes (100 W, 500 W, and
      1000 W) of tungsten-filament lamp standards of total irradiance. These standards
      operate at a higher temperature than was possible with the carbon-filament lamps,
      and are shielded, except for a narrow area of the bulb in front of the filament,
      so the reception of long wavelength flux from the lamps is reduced to a minimum.
      The new lamps were calibrated by the use of a blackbody at a known temperature
      together with a quartz plate whose spectral transmittance was accurately
      determined. The quartz plate limits the flux received from the blackbody to the
      spectral region below about 4.5 micro and thus reduces errors resulting from
      water vapor absorption at 6 micro and longer wavelengths. Comparisons sow the new
      standards to be in close agreement with the carbon-filament lamp standard.

PMID- 20057702
TI  - The cost of applied optics.

PMID- 20057703
TI  - Some approximations to the planck function in the intermediate region with
      applications in optical pyrometry.
AB  - For many applications, a simple approximate equation for blackbody radiation can
      be more useful than is the Planck blackbody equation. An intermediate region
      exists where both the Rayleigh-Jeans equation and the Wien equation for blackbody
      radiation are inaccurate approximations to the Planck equation. Several
      approximate equations of simple mathematical form have been obtained that are
      more accurate in this intermediate region. These equations are applied to optical
      pyrometry to obtain formulas for brightness temperature and color temperature
      that can be used in the intermediate region.

PMID- 20057705
TI  - Approximate normal emissivity spectra in the infrared at elevated temperatures of
      single-crystal and polycrystalline calcium fluoride.
AB  - A single-beam ir spectroradiometric system has been used to measure the normal
      spectral emissivity of specimens of single-crystal and polycrystalline calcium
      fluoride in the ir at elevated temperatures. The wavelength range was 2-12 micro,
      and data were taken at sample temperatures of 500 degrees C and 600 degrees C.
      Room temperature data on the index of refraction of single-crystal calcium
      fluoride and its rate of change with temperature were extrapolated to 500 degrees
      C and 600 degrees C; the normal spectral reflectivities were computed from the
      extrapolated indices at these temperatures. Then the computed reflectivities were
      used to extract normal spectral absorption coefficients from the emissivity data.
      It was possible to compute absorption coefficients with reasonable accuracy at
      wavelengths of 6 micro, 8 micro, and 10 micro; the smallest estimated error was
      about 2% at 8 micro. The absorption coefficients increased markedly with
      temperature at these three wavelengths. The absorption coefficients of the polycr
      stalline material were consistently higher than the corresponding values for the
      single-crystal calcium fluoride. It was found that the spectral absorption
      coefficients at 8 micro and 10 micro microns varied approximately as the 2.1 and
      1.6 power of the absolute temperature, respectively, between room temperature and
      600 degrees C. These exponents lie within the range predicted by theory.

PMID- 20057706
TI  - Generalized integrating-sphere theory.
AB  - A general equation is developed for the efficiency of an integrating sphere with
      a nonuniform coating. The only assumptions are that the interior is a perfect
      sphere and that all areas reflect perfectly diffusely. Three special cases of the
      general equation are examined for the basic applications of integrating spheres
      as mixing mechanisms in hemispherical reflectance measurements and in absolute
      reflectance techniques.

PMID- 20057707
TI  - Resolving power predictions from lens design data.
AB  - A relationship between longitudinal spherical and longitudinal chromatic
      aberration and resolving power is discussed and an experiment using this
      relationship to predict resolving power from design data is described. The
      results show a high degree of correlation between resolving power predicted by
      this method and that obtained by measurement on real lenses.

PMID- 20057708
TI  - OSA Technical Groups.

PMID- 20057709
TI  - A new interferometer capable of measuring small optical path differences.
AB  - This paper reports the development of a new type of interferometer capable of
      measuring optical path differences of lambda/1000 or less. Experiments that
      verify this capability were performed and are reported. The interferometer
      exhibits, in addition to a high sensitivity, an advantage of increased
      environmental stability over more conventional interferometers which depend upon
      optical path changes manifested as fringe shifts.

PMID- 20057710
TI  - Spectral line broadening in air molecule systems.
AB  - Broadening of the spectral lines by resonance and Van der Waals forces in the
      Schumann-Runge system of O(2), the first and second positive systems of N(2), the
      beta and gamma systems of NO and the first negative system of N(2)(+) is treated
      by means of the impact approximation. At temperatures of 1000 degrees K and
      higher, the broadening effect of the resonance forces is negligible; there is
      hence no J dependence in the widths. Van der Waals constants are calculated for
      the electronic-vibrational levels of interest using available discrete and
      continuous oscillator strengths. Half-widths in the various systems have been
      computed for 0 <or= nu, nu' <or= 12, 1000 degrees K T 18,000 degrees K and
      rho/rho(0) = 10,10(-1). In general, there is not much width variation with
      vibrational band in a system.

PMID- 20057712
TI  - An optical power limiter.

PMID- 20057711
TI  - The detectivity of electron beam scanning types of image tubes.
AB  - A theoretical development has been applied to vidicon and orthicon types of image
      tubes which is similar to that used for ir photodetectors. In essence, a
      differential equation applicable to these image tubes has been used to obtain
      exact solutions for signal and noise. These expressions account for factors such
      as storage, frequency response, resolution, and efficiency. They can be inserted
      into the usual definitions of noise equivalent power, detectivity star, and
      detective quantum efficiency to provide exact expressions indicating the
      dependence of these quantities on basic factors governing tube generation.
      Experimental procedures are proposed for making signal and noise measurements
      which provide information directly comparable to those for photodetectors.

PMID- 20057713
TI  - Correcting for astigmatism in the czerny-turner spectrometer and spectrograph.

PMID- 20057714
TI  - Improvement of imagery in rotating mirror cameras by helium atmosphere.

PMID- 20057715
TI  - Multiplier phototubes as quantum counters.

PMID- 20057716
TI  - Object-image Relationships in Scattered Laser Light.

PMID- 20057717
TI  - Damage in glass induced by linear absorption of laser radiation.

PMID- 20057718
TI  - The ultraviolet filtering properties of the alkali-halide vapors and Cl(2).

PMID- 20057719
TI  - Experiments on the interaction of Lyman alpha radiation and atomic hydrogen.

PMID- 20057720
TI  - On the calculation of thin film refractive index and thickness by ellipsometry.

PMID- 20057721
TI  - A method for finding white light fringes useful in interferometers.

PMID- 20057723
TI  - Fourier transform spectrometer-radiative measurements and temperature inversion.

PMID- 20057724
TI  - Comments on a double grating monochromator with no tracking error by H. I.
      Mandelberg.

PMID- 20057725
TI  - Balloon telescope optics.
AB  - The article deals with optical problems associated with making infrared
      astrophysical observations with a balloon-borne telescope. Advantages and
      difficulties associated with such high altitude observations are reviewed. Topics
      treated are incandescence of components of the instrument in the infrared,
      infrared resolving power in the laboratory contrasted with that in the
      observatory; data documentation; collimator/planet-simulator; novel balloon
      telescope, and corrections of spherical aberration therein; vignetting and
      focusing; astigmatism correction; image slicer; grating spectrometer, and
      correction of aberrations therein; Benedictine slits; and detector-refrigerator
      and its optics.

PMID- 20057726
TI  - A balloon-borne grating spectrometer.
AB  - A balloon-borne, 0.5-m, Czerny-Turner grating spectrometer has been designed and
      constructed at the University of Denver and has measured atmospheric
      transmittance in several spectral regions between 2 micro and 14 micro. These
      data have been obtained on a series of eleven balloon flights at three geographic
      locations over a period of thirty months. The solar pointing system, spectrometer
      optics, electronics and recording system are described. The preflight and flight
      performance of the spectrometer is discussed and sample data presented.

PMID- 20057727
TI  - Direct solar radiation up to 30 km and stratification of attenuation components
      in the stratosphere.
AB  - The balloon apparatus and some of the results of the direct solar radiation
      investigations up to 30 km in the middle belt of the Soviet Union in 1961-1965
      are briefly described. Measurements of total direct solar radiation showed that
      the aerosol extinction properties in the free atmosphere are rather considerable,
      not only up to 30 km but also at the higher levels. The layered character of the
      stratospheric optical structure is demonstrated. The dynamics of layers and the
      possible influence of volcanic activity is discussed. Spectral investigations in
      the 0.35-13 micro region demonstrated that the stratospheric humidity is small,
      approximating 10(-6)-10(-5) g/g. The measurements in the visible spectrum
      confirmed that stratospheric aerosol component is essential, the stratospheric
      optical density being about 10(-4)-10(-3) km(-1). Comparison of the results of
      spectral and integral investigations indicates that the aerosol ext nction is
      also dominant above 30 km.

PMID- 20057728
TI  - Fourier spectrometry from balloons.
AB  - Some considerations on the design and construction philosophy of balloon-borne,
      high-resolution, Fourier interference spectrometers are presented in the context
      of a far ir Michelson interferometer and a near ir double-passed cat's-eye
      interferometer. The far ir instrument has already flown, with some success. The
      other is currently under development for a future flight.

PMID- 20057729
TI  - Guiding of balloon-borne telescopes by off-set sun-tracking.
AB  - Two methods of off-set sun-tracking are described which were developed as part of
      the balloon-astronomy program of The Johns Hopkins University for daytime
      observations of the planet Venus. The performance of the system in flight, while
      subject to oscillations in the suspension system, is discussed.

PMID- 20057730
TI  - An optical art.

PMID- 20057731
TI  - A research program aimed at high altitude balloon-borne measurements of radiation
      emerging from the earth's atmosphere.
AB  - The relevance of polarization measurements in the near uv and visible regions of
      the electromagnetic spectrum in investigations of the effects of the atmospheric
      aerosol and the reflective properties of the ground, intermediate layers of the
      atmosphere, and the atmosphere as a whole on the ambient radiation field is
      discussed. The salient features of a photoelectric skylight polarimeter
      characterized by its adaptability to balloon-borne measurements of the degree of
      linear polarization and relative intensity variations in four narrow spectral
      intervals (bandwidth approximately 150 A) centered on lambdalambda 3270 A, 3975
      A, 500 A, and 6120 A are described. Preliminary results of measurements obtained
      in a balloon experiment staged at Page, Arizona (36 degrees 57'N, 111 degrees
      27'W, 1300 m above msl) on 30 March 1965 are presented.

PMID- 20057732
TI  - Balloon observations of the radiance of the earth between 2100 cm(-1) and 2700
      cm(-1).
AB  - A grating spectrometer capable of measuring small radiation fluxes with a
      spectral resolution of 95 at 4.3 micro is described. Bands of CO(2), N(2)O, and
      O(3) are identified in spectra between 2100 cm(-1) and 2700 cm(-1) of the earth
      and lower atmosphere obtained from an altitude of 30 km with this instrument.
      Scattering of solar radiation by clouds was observed between 2400 cm(-1) and 2700
      cm(-1). A temperature profile of the atmosphere to 30 km determined from an
      analysis of the measurements in the region of the 4.3 micro CO(2) band is
      compared with radiosonde observations made during the flight.

PMID- 20057734
TI  - Applied optics of optics and opticists.

PMID- 20057733
TI  - Ultraviolet polarimetry using high altitude balloons.
AB  - The ozone and oxygen in the earth's atmosphere prevent all ground-based observing
      at wavelengths shorter than about 3000 A. With the largest available balloons and
      a large telescope one can get sufficiently above the ozone to make precise
      polarization measurements of stars and planets near 2820 A and 2200 A. Two
      telescope/gondola systems are in operation. The first actually is a prototype for
      spacecraft but it is also used on balloons, mounted in a gondola of the National
      Center for Atmospheric Research. It has two 7.5-cm reflecting telescopes (7.5 cm
      is the diameter of the primary mirror). The second system has a 71-cm Cassegrain
      reflector, two vidicon cameras, command and telemetry by radio link, and a
      startracker that guides the stabilized platform (+/-1 min of arc). The first
      measurements made were of the polarization of the moon at 2900 A in December
      1965, and of interstellar polarization at 2820 A and 2200 A in May 1966.

PMID- 20057735
TI  - Improvements to a balloon-borne sun-seeker.
AB  - A commercial balloon-borne sun-seeker has been improved in several ways. Power
      consumption is reduced by using transistorized circuits and solid state switches
      instead of tubes and magnetic clutches. Silicon cells used as fine pointing
      sensors are moved near the entrance slit of the spectrometer to eliminate the
      effects of optical misalignment. Operational amplifiers provide weighted sums of
      the error signals for pointing. The gains of the servo system are controllable by
      radio command.

PMID- 20057736
TI  - Photomultiplier tubes for Satellite instrumentation.
AB  - The rapid increase in the use of photomultiplier tubes (PMT's) in satellite
      instrumentation has created the need for a practical engineering discussion of
      their application as circuit components. This paper discusses the basic theory of
      operation and stresses their measurable parameters needed in specifying and
      applying them in instrumentation systems. Results of unique experiments to
      determine recovery time after exposure to light or temperature are given. Various
      protective measures, required for safe operation of the PMT's are discussed.
      Finally, a specific application of a PMT to the PEP/OAO Satellite Program is
      discussed. Examples of the necessary design equations and constraints are given
      and actual performance characteristics stated.

PMID- 20057737
TI  - Heterodyne and photon-counting receivers for optical communications.
AB  - The relative performance of an optical heterodyne receiver and a photon-counting
      receiver are compared. These conditions under which the two types of systems
      perform equally well are defined. Background noise is shown to be an almost
      negligible consideration. Detector noise is seen to be a much more severe
      problem. It is concluded that for wavelengths below 1 micro, photon-counting
      reception is preferred because of the availability of photoemissive detectors.
      For wavelengths greater than 3 micro detector noise considerations are so severe
      that it is unlikely that photon counting will be competitive with heterodyne
      detection. The type of detection preferred in the 1-3 microrange is shown to be a
      matter of detector development.

PMID- 20057738
TI  - Threshold sensitivity and noise ratings of multiplier phototubes.
AB  - This paper deals with the various methods of specifying the noise characteristics
      of multiplier phototubes. Particular attention is paid to the different sources
      of noise, including thermionic emission from the photocathode, spurious dark
      emission, leakage current, background flux, and the random photon fluctuation of
      the signal flux itself to be detected.

PMID- 20057739
TI  - Optimizing the operating parameters of infrared spectrometers.
AB  - In order to achieve best results with modern ir spectrometers, users must take
      considerable care to optimize the setting of the slit program, response time,
      gain, and scan time. In this paper, explicit recommendations are given for
      carrying out such adjustments in a logical and self-consistent manner. First, a
      set of conditions is derived for the recording of general purpose spectra. From
      this starting point, settings may be modified to record spectra under the
      following special conditions: low noise level, limited optical energy, high
      resolution, and rapid scanning. Proper use of the scan speed suppression control
      is discussed.

PMID- 20057740
TI  - A rapid-scan spectrometer that sweeps corner mirrors through the spectrum.
AB  - By sweeping a sequence of corner mirrors through an intermediate focal plane, a
      grating spectrometer can be converted to rapid scanning without loss of optical
      quality. We have developed an instrument using this principle to scan the first
      order spectrum of a diffraction grating in 1 msec, at rates up to 800 scans/sec.
      In our design, twenty-four corner mirrors are mounted on the periphery of a
      dynamically balanced rotating scan wheel, tangential to the intermediate focal
      plane of a double-pass CzernyTurner monochromator. Specific features include
      readout linear in time and wavelength, foreoptics focusable from 28 cm to
      infinity, absolute radiance calibration, and interchangeable gratings and
      detectors for the region 2500 A to 9 micro. Performance is limited only by the
      detector signal-to-noise ratio determined by the scan time and the electrical
      bandwidth required, and is not limited by the optical scanning technique. Spectra
      illustrating instrument performance are presented.

PMID- 20057741
TI  - Computer calibration of the wavelength drive of a prism spectrometer.
AB  - The Sellmeier equation has been slightly modified to describe the drum position
      as a function of frequency for a Littrow type prism spectrometer. A widely
      available IBM Share program in Fortran II can be quickly and easily adapted to
      fit calibration data to this equation. The program provides a least-squares
      estimate of the constants in the equation when two of the constants, the curve
      asymptotes, are moderately well estimated. When this method was applied to a
      thermostated Perkin-Elmer model 99 double-pass monochromator, the resulting
      standard deviation sigma between data points and computed points was only
      slightly larger than reading repeatability. Prisms used were SiO(2), CaF(2),
      NaCl, KBr, and CsBr. The best fit was obtained for NaCl with sigma = 0.25 drum
      numbers between 1.4 micro and 13.7 micro. The maximum sigma obtained was 0.72
      drum numbers for KBr in the 10-22 micro range, which corresponds to a standard
      deviation in wavelength of 0.01 micro. Using the calculated dispersion constan, a
      second program prints a table of drum numbers vs wavelength and wavenumber at
      intervals as small as the error in the fit will allow. This table is an accurate
      and convenient substitute for the wavelength calibration graph.

PMID- 20057742
TI  - A high resolution rapid-scanning spectrometer.
AB  - A Czerny-Turner type spectrometer has been designed and operated as a rapid
      scanning instrument by placing a rotating mirror near the exit slit. Using a
      helium-neon gas laser, resolution of 0.027 A has been measured at scanning rates
      of 0.4 A/microsec. Data have been taken with the scanning rate of 6 A/microsec,
      which could have been increased an order of magnitude if desired. A scanning
      range of 1-600 A depending on the grating and mirrors used has been obtained.
      Applications shown included the shift and shape of xenon spectral lines in a
      pulsed arc discharge. The associated electronics required for synchronization are
      included.

PMID- 20057743
TI  - Fabry-Perot interferometers with electronic determination of Doppler line widths.
AB  - It is shown that, if Fabry-Perot interferometers are to be used for the
      measurement of doppler widths of emission lines, exact knowledge of the plate
      reflectivity is required so that synthetic profiles may be calculated. If
      hyperfine structure or isotope structure is present, the data reduction may be
      tedious. It is shown that electronic analysis of the signal generated by a
      scanning interferometer will lead directly to a displayed measurement of the
      doppler temperature, and that the effects of hyperfine structure, isotope
      structure, Lorentz broadening, nonflatness of the plates and the finite size of
      the scanning aperture may all be compensated exactly. The performance in marginal
      circumstances has been calculated using the derived equations, and the system is
      shown to be capable of high accuracy.

PMID- 20057744
TI  - Multilayer interference filters with narrow stop bands.
AB  - Multilayer interference filters having various transmission characteristics are
      described and compared. The emphasis is on filters with narrow stop bands such as
      might be used to eliminate the hazard from a laser beam. Four types of filters
      are considered: (1) quarter-wave stacks of two dielectric materials having
      matching layers one-eighth wavelength thick; (2) quarter-wave stacks of two
      dielectric materials having all layers of the same optical thickness (including
      the end layers); (3) quarter-wave stacks wherein all layers are of the same
      optical thickness, but the refractive indices of the layers may all be different
      to achieve equal reflection ripples in the passband; and (4) multilayer stacks of
      two dielectric materials wherein each layer may be of a different optical
      thickness to achieve nearly equal reflection ripples in the passband. The new
      formulas presented give the bandwidths between nulls of all the various filters
      as well as the bandwidths between equal-ripple points of the equal-ripple filter.
      Explicit formulas are stated for the ripple envelopes of filter types (1) and
      (2), and for the ripple heights of equal-ripple filters of types (3) and (4). A
      first-order design procedure based on the theory of linear arrays is given and
      evaluated by working numerical examples; general design criteria are presented to
      establish the validity of the first-order theory.

PMID- 20057745
TI  - Zone plate theory based on holography.
AB  - A series representation developed from holography theory is used to determine the
      image distances and relative image intensities for three types of zone plates.
      The effect of nonlinearity in film reproduction on the hologram of a point object
      and the images produced by this hologram are discussed.

PMID- 20057746
TI  - [Dirichlet's Theorem].
AB  - In the introduction to Chapter II of his work L'Integrale de Fourier et ses
      Applications a l'Optique, Duffieux reduces Dirichlet's Theorem to a "specific
      summary." Developed by a convolution where the functions of influence apply [Rev.
      Opt. 34, 351 (1960)], Dirichlet's Theorem immediately gives data on the form of
      two functions that the Fourier transform introduces in Fraunhoffer diffraction at
      infinity. The distribution plane, where one normally cuts off Huygens' pupils,
      F(x,y), is composed not of points, but of diffraction figures or correlation
      functions. The function f(u,v) of a spread of frequencies is also a directive
      function, but it shows no correlation and has discontinuities. F(x,y) is linked
      with the undulatory theory of light, and f(u,v) represents a corpuscular flux.
      Two conclusions can be drawn therefrom: (1) the limited pupils must, correctly,
      be defined by the directive function f(u,v); (2) Fourier's equation establishes a
      relation between two aspects of the propagation of the lig t crossing a plane,
      one of which conforms to the undulatory theory of light, the other to his
      corpuscular theory. We are visibly lacking a corpusculatory theory of light and
      its coherent images.

PMID- 20057747
TI  - A rational function approach to multilayer synthesis.
AB  - The transformation S = jomega, omega = -cotphi of the interference phase angle
      phi = 2pinhlambda(-1) is applied to the matrix of a thin dielectric film. This
      brings the complex coefficients of reflection and transmission to the form of
      rational functions, whose coefficients are built up from the refractive indices.
      Matching to a given spectral characteristic may be performed by any of the
      approximation methods of network theory. An algorithm is derived for the
      computation of the refractive indices from the coefficients of these rational
      functions. Connection with other synthetic methods for thin films is also
      indicated. Illustrative examples are included.

PMID- 20057748
TI  - Anisotropy in alphanumeric reproduction tolerances.
AB  - The relative importance of spatial image characteristics in the reproduction of
      alphanumeric characters has been examined, and it is concluded that significant
      anisotropy exists. At low distortion levels, horizontal image degradation is
      somewhat less objectionable than vertical degradation, but at higher levels
      vertical distortion is significantly less objectionable. The upper and lower
      portions of characters are found to be much more important for legibility than
      are the central portions. Upper portions of characters carry more legibility
      information than the lower portions. The implications of these findings on image
      transmission systems are discussed.

PMID- 20057749
TI  - Frictionless bearing for balloon.

PMID- 20057751
TI  - Criteriia for accuracy of measurement of line intensities and mean absorption
      coefficients.

PMID- 20057752
TI  - Increased ultraviolet sensitivity in the sodium salicylate-photomultiplier
      combination.

PMID- 20057753
TI  - Performance of LiTaO(3) and LiNbO(3) light modulators at 4 GHz.

PMID- 20057754
TI  - Gas prism for light beams.

PMID- 20057755
TI  - A programmed multipulse range measurement system.

PMID- 20057756
TI  - Analysis of a modified frustrated total reflection filter.

PMID- 20057758
TI  - A high-temperature blackbody radiation source.

PMID- 20057757
TI  - Multiple beam interference in opaque photocathodes.

PMID- 20057759
TI  - Noise factor measurements in multiplier phototubes.

PMID- 20057760
TI  - Double beam operation of a Fourier spectrometer.

PMID- 20057761
TI  - An echelle spectrograph for middle ultraviolet solar spectroscopy from rockets.
AB  - An echelle grating spectrograph is ideal for use in a rocket when high resolution
      is required becaus itoccupies a minimum of space. The instrument described covers
      the range 4000-2000 A with a resolution of 0.03 A. It was designed to fit into
      the solar biaxial pointing-control section of an Aerobee-150 rocket. The
      characteristics of the spectrograph are illustrated with laboratory spectra of
      iron and carbon are sources and with solar spectra obtained during rocket flights
      in 1961 and 1964. Problems encountered in analyzing the spectra are discussed.
      The most difficult design problem was the elimination of stray light when used
      with the sun. Of the several methods investigated, the most effective was a
      predispersing system in the form of a zero-dispersion double monochromator. This
      was made compact by folding the beam four times.

PMID- 20057762
TI  - Atmospheric scattering of the solar flux in the middle ultraviolet.
AB  - Spectra in the middle uv obtained on a rocket flight by a spectrometer pointed
      downward at the earth are compared with synthetic spectra generated by a
      computer. The independent variables of the synthetic spectra are the altitude of
      the detector, the wavelength, the zenith angles of the sun and of the detector
      line-of-sight, the azimuth difference between them, and three parameters
      characterizing the ozone distribution. In the altitude range of primary interest
      only two of the ozone parameters are free. Taken into account are the roundness
      of the earth, first-order Rayleigh scattering by the atmosphere, attenuation by
      air, absorption by molecular oxygen and ozone, and the line structure in the
      solar spectrum. The effects on the synthetic spectra of varying the parameters of
      the ozone distribution and the geometric parameters are also studied.

PMID- 20057763
TI  - Detectors for the extreme ultraviolet. I: photomultipliers used in the dc output
      current mode.
AB  - An investigation has been made of voltage-sensitivity characteristics, absolute
      spectral response, dark current and output current limitations of seven
      photomultipliers suitable for detection of extreme uv radiation. These
      photomultipliers are windowless types, utilizing cathode surfaces blind to
      visible and near uv radiation; they include a microminiature continuous channel
      multiplier. For measurements of absolute spectral sensitivity, they were compared
      to a conventional 1P21, coated with sodium salicylate which, in turn, had been
      calibrated at 1216 A with a nitric oxide ionization chamber. The spectral
      response measurements cover the spectral region from 1500 A to 584 A. The
      photomultipliers were used in a dc output currrent mode and were excited with
      radiation from both pulsed and dc gas discharge sources. A discussion of the
      suitability of the detectors for use with each type of source is given.

PMID- 20057764
TI  - Absorption coefficient and photoionization yield of NO in the region 580-1350 A.
AB  - Photoionization yield and absorption coefficient of nitric oxide were measured at
      many wavelengths in the region 580-1350 A. H emission and helium continuum
      sources were used with a 1-m monochromator. Absolute intensity measurements were
      based on a calibrated thermocouple.

PMID- 20057766
TI  - OSA research and education.

PMID- 20057765
TI  - Ultraviolet measurements in planetary atmospheres.
AB  - The impact of the latest optical and electronic component developments on far uv
      rocket spectrophotometry is discussed. Results of some recent experiments
      studying earth airglow and aurorae are reviewed. It is shown that weaker spectral
      features can he measured in the region 1100 A to 3000 A than at any longer
      wavelength.

PMID- 20057767
TI  - Vacuum ultraviolet research.
AB  - Some applications of vacuum uv radiation to basic research problems are
      discussed, with emphasis on the interaction of vacuum uv radiation with gases and
      solids.

PMID- 20057768
TI  - [Source for spectrography in uv region].
AB  - A simple source for spectrography in the far uv region is described; in this
      source the discharge of a capacitor in a capillary tube is triggered (without
      introduction of gas) by a sliding spark, even when there is a good vacuum in the
      capillary. According to the characteristics of the high voltage power supply,
      either a line spectrum or a continuous spectrum is obtained. The pulse repetition
      frequency and stability of the source allow recording with a standard
      potentiometric chart recorder.

PMID- 20057769
TI  - A high intensity flash lamp for vacuum ultraviolet photochemical studies.
AB  - A simple flash photolysis lamp has been described. This lamp has output in the
      vacuum uv region down to LiF cutoff and has been used successfully in the
      photodecomposition of ethane. The output intensity was measured below 1650 A
      using carbon dioxide as an actinometer and was found to be 7.2 x 10(16)
      quanta/flash or 1.31 x 10(21) quanta/sec. This intensity is about a factor of
      10(6)-10(7) higher than that of the low intensity vacuum uv lamp normally used in
      the continuous photolysis technique.

PMID- 20057770
TI  - Measurement of short luminescence decay times.
AB  - The stroboscopic technique for measuring luminescence decay times and for time
      resolved spectroscopy can be greatly simplified by using a photomultiplier which
      has a control mesh behind the photocathode. This makes it possible to cut off the
      tube output by applying a negative bias of 1-2 V to the mesh; then the tube can
      be gated on for short periods by applying a positive pulse of slightly higher
      amplitude. This eliminates the problems encountered with gating methods, in which
      high voltage pulses are applied to the photomultiplier dynodes. Measurements were
      made on two fast decay phosphors (P-15 and P-16), and the results show that this
      tube is quite suitable for this purpose.

PMID- 20057771
TI  - Measurement of ruby laser cavity losses by Fabry-Perot resonance.
AB  - Determinations of optical loss in unpumped ruby laser crystals from measurements
      of the transmissivity vs optical path length (as changed by temperature) using an
      amplitude regulated, single mode, He-Ne laser beam probe are described. Excellent
      agreement between these measurements and the theory of Dufour and Picca was
      obtained for a flux-grown ruby using as-grown feedback surfaces. The essentially
      zero loss per pass beta (apart from end reflector losses) deduced from this
      comparison is in excellent agreement with a previous determination of the loss in
      this crystal from laser threshold measurements. The reduction of the effective
      surface roughness by deposition of multilayer zinc sulfide-cryolite reflectors
      was observed in these experiments. For a high quality, 7.5-cm long, 0.05 wt%
      Cr(2)O(3), 60 degrees orientation ruby rod, beta was found to be 0.03 +/- 0.03.
      For a 90 degrees orientation, 2.2-cm long, trumpet-shaped ruby used for
      continuous operation threshold studies, beta was found to be about 0.14. The
      problems of this type of loss measurement when index of refraction variations are
      present are discussed, and observations connecting the crystal quality and laser
      mode characteristics are presented.

PMID- 20057772
TI  - Measurement of the room temperture R(1) line width of forty-two rubies.
AB  - Accurate measurement of the room temperature R(1) fluorescent line width of forty
      two ruby laser crystals has been made using a pressure-scanned Fabry-Perot
      etalon. In forty-one of these rubies the chromium content was nearly the same,
      and the R(1) line width for all was 5.0 +/- 0.3 A, in agreement with present
      theories.

PMID- 20057773
TI  - Laser mode selection by internal reflection prisms.
AB  - Internal reflection prisms were used to produce a narrow angular range of high
      reflectivity within a laser cavity. The selectivity was obtained from the sharp
      angular variation of internal reflectivity near the critical angle. Angular mode
      selection of a Nd: glass normal laser was achieved by this critical internal
      reflection (CIR) technique. Two-dimensional angular mode selection was observed
      with two orthogonal Lummer-Gehrcke plates within the laser cavity.

PMID- 20057774
TI  - Optical electronics.

PMID- 20057775
TI  - Multiple pass effects in high efficiency laser pumping cavities.
AB  - Some effects connected with multiple passes of pump radiation in laser pump
      cavities are discussed. These effects include changes in mercury arc lamp
      operating characteristics, when the lamps are used inside the cavities as pump
      sources, and unexpectedly low pulse (but not cw) thresholds in double elliptical
      cavities. It is shown analytically that these effects can, at least in part, be
      attributed to the shapes of the pump light energy distribution curves after
      multiple passes through the pump cavities, and to the relative opacities of flash
      and continuous lamps.

PMID- 20057776
TI  - Analysis of a multiple reflective translucent photocathode.
AB  - In order to evaluate methods of enhancing the response of state-of-the-art
      photocathodes, such as the S-20, we have used a mathematical absorption-diffusion
      model to study the effects of skewed incidence of light on the quantum
      efficiency. The phenomenon of increased optical absorption due to multiple
      reflections of light within the emitting layer-glass substrate combination is
      treated as a function of the angle of incidence. When the quantum efficiency
      generated for skewed incidence is compared with the quantum yield generated for
      normal incidence, a gain of 3.5 is predicted. The gain is greatest for the
      smallest absorption coefficient-photocathode thickness product.

PMID- 20057778
TI  - OSA technical groups.

PMID- 20057777
TI  - Self modulating, derivative optical spectroscopy. Part II: experimental.
AB  - The present paper follows a previous one that dealt with the theoretical
      principles of a self modulating derivative optical spectrometer (SMODOS). In this
      paper the complete description is given of a prototype of such an instrument,
      namely, of its optical as well as electronic components. The project criteria are
      thoroughly discussed, and some examples of performance that demonstrate the power
      of the method are presented.

PMID- 20057779
TI  - A Littrow-McCubbin high resolution infrared spectrometer.
AB  - We have recently built a vacuum infrared spectrometer with demonstrated
      capability of resolving 0.03 cm(-1). The instrument is designed around a 2.5-m
      Littrow-McCubbin monochromator and has an effective range of from 1-40 micro. The
      design, construction, and performance of the instrument are described.

PMID- 20057780
TI  - An improvement in Fabry-Perot spectrometry.
AB  - In Fabry-Perot interferometry a large fraction of light can be reflected by the
      etalon; thus, it is lost for spectroscopic purposes. The present article shows
      the possibility of recovering this light, collecting it by means of reflectors
      and sending it back to the etalon under a different angle. Some devices are
      examined and some experimental proofs of the device are reported. The gain
      achieved is of the order of five.

PMID- 20057781
TI  - Effective refractive indices of metal-dielectric interference filters.
AB  - It is shown that the performance of metal-Perot and Sp acerless Induced
      Transmission types in parallel radiation incident obliquely can be described in
      terms of that of a single equivalent dielectric layer of refractive index
      micro(E). Expressions for micro(E) are deduced in terms of the optical constants
      of the layer materials, and their validity is established by the satisfactory
      agreement that is shown to exist between experimental and calculated values of
      micro(E).

PMID- 20057782
TI  - Measurement of cell thickness in infrared spectrophotometry.
AB  - It is shown that the usual expression for measuring the cell thickness d(a) of an
      empty cell, namely, d(a) = lambda(1)lambda(2)N/2(lambda(2) - lambda(1)), where N
      is the number of fringes over the wavelength range lambda(1) and lambda(2), may
      only be applied under particular conditions of cell and wall thickness and
      spectrophotometer characteristics. This is done by first deriving the expression
      for the transmission coefficient of a cell taking into account all the four
      surfaces at which a discontinuity in the refractive index occurs (while in
      deriving the above formula only two such surfaces are considered). Then, by
      examining the spectrophotometer characteristics, we investigate what amount of
      the information contained in the variation of transmission coefficient with
      wavelength is actually recorded by the instrument. Formulas are developed for
      different situations, in which only cell thickness, both cell and wall thickness,
      and finally only wall thickness, may be measured by counting the number of
      fringes over a wavelength interval. The equation mentined at the beginning is
      only valid for the first of these cases.

PMID- 20057783
TI  - Infrared absorption by overlapping bands of atmospheric gases.
AB  - The spectral transmission of carbon monoxide, nitrous oxide, and mixtures of the
      two has been studied in the 2200-cm(-1) region, where overlapping absorption
      bands occur. With spectral slit widths sufficiently large to include several
      absorption lines, it was found that the observed spectral transmittance of a
      mixture is equal to the product of the transmittances of the components measured
      separately, provided that sufficient nitrogen is added to give the same total
      pressure for all samples. This result was also obtained for overlapping bands of
      nitrous oxide and methane in the 1300-cm(-1) region. The present work confirms
      Burch's earlier studies of overlapping bands of CO(2) and water vapor. An
      investigation of the possible breakdown of the multiplicative property of
      transmission for narrow spectral slit widths was inconclusive.

PMID- 20057784
TI  - Near infrared atmospheric absorption over a 25-knm horizontal path at sea level.
AB  - Atmospheric absorption spectra obtained over a 25-km, horizontal, sea level path
      in the Cape Kennedy area are presented. Six 150-cm diam carbon are searchlights
      positioned from 11 m to 17 m above the ground were used as sources of continuous
      radiation. Solar spectra obtained from sea level are traced above the
      corresponding horizontal path spectra for comparison. The spectral region covered
      is 0.68 micro to 4.86 micro and the spectral resolution varies over this region
      from about 0.6 x 10(-4) micro to 60 x 10(-4) micro. The amount of water vapor in
      the path varied from 9 to 39 precipitable cm.

PMID- 20057785
TI  - Optical effects of thermal structure in the lower atmosphere.
AB  - Ascending convective plumes of inhomogeneous warm air interspersed with regions
      of air that are remarkably free from temperature fluctuations are sometimes
      observed in the lower layers of the atmosphere. A close correlation is
      demonstrated between intervals of good optical seeing along an upwardslanting
      path 20 m long and such periods of below average, air-temperature fluctuation.
      This correlation is sensitive to the azimuthal angle between wind direction and
      the vertical plane containing the optical path. The occurrence of temperature
      quiescent periods at a given height is also shown to require the horizontal wind
      speed to be less than a critical value, and there is evidence that the thermal
      structure tends to be elongated in the direction of the wind. The range of
      amplitudes of image dancing observed in these experiments is comparable with that
      encountered in solar observations. The atmospheric temperature structure
      coefficients calculated from these optical experiments compare favorably with
      independent direct measurements.

PMID- 20057786
TI  - Enhancement of fine detail in the presence of large radiance differences.
AB  - A technique is described for enhancing fine detail in the production of radiance
      pictures of targets in which large differences also occur, and where the dynamic
      range of the picture viewing system is limited. This is achieved by scannig a
      raster with a mirror-chopper fed detector over the target area, and referencing
      one sampled area on this target against the next, the radiance intensity from
      which is reduced by a constant factor. The detector output is then a difference
      curve related to a derivative trace of the radiance profile, superimposed on the
      true radiance profile reduced in intensity. The method is compared with a similar
      technique previously used by Low(2), and examples of the use of the present
      technique both in the laboratory and in observing a feature on the lunar surface
      are included.

PMID- 20057787
TI  - Analytical and experimental investigation of light scattering from
      polydispersions of Mie particles.
AB  - A comparison has been made between (1) the computed angular scattering
      coefficient for a polydisperse cloud of small, spherical (Mie) particles and (2)
      the measured angular scattering coefficient for a polydisperse cloud of
      irregular, randomly oriented (Mie) particles fitting the same distribution
      function and having the same material properties. The comparison has been made
      for eight wavelengths covering the visible range.

PMID- 20057788
TI  - Application of hologram techniques for particle size analysis.
AB  - The basic principles of applying hologram techniques to the problem of particle
      size determination have received considerable attention over the past year. In
      this paper the basic principles of the use of the Fraunhofer (far field) hologram
      are described for both the recording of the hologram and the reconstruction of
      the particle distribution. Factors affecting the sample volume depth and particle
      size range are discussed. Typical results are shown.

PMID- 20057790
TI  - Multicolor wavefront reconstruction.
AB  - Two and three primary colors derived from an He-Ne gas laser and an argon gas
      laser were employed in recording and reconstructing holograms. For the tricolor
      case it is possible to reconstruct a three-dimensional multicolor image which
      possesses almost all the natural hues of the original object. Each wavelength
      generates an independent fringe system that is recorded on a photographic plate
      with a thick emulsion that constitutes a three-dimensional recording medium. In
      reconstruction, each fringe system diffracts light in a manner satisfying the
      Bragg relation for a particular reconstructing wavelength. If the reconstruction
      wavelengths are the same as the original wavelengths used to record the fringe
      systems, the result is a multicolor reconstruction possessing few or no ghost
      images. In our experiments, the angle between the object beam and the reference
      beam was greater than 100 degrees , and the photographic plates were oriented so
      that the fringe surfaces were approximately perpendicular to the emulsion surfac
      This minimized the deleterious effects of single-color, ghost image formation and
      shrinkage during development. Finally, a method of synthesizing multicolor scenes
      using a multiple-exposure recording with one wavelength and reconstructing with
      several wavelengths is described.

PMID- 20057791
TI  - Operator formulation of plane mirror systems.
AB  - A terminology limited to point objects is introduced to distinguish between
      finite and infinite, transparent and opaque mirrors. A basic image-producing
      operator is defined, and its properties are examined in detail. An operational
      form of the basic operator is derived, two general definitions are presented, and
      a formal expression for the images of a system of plane mirrors is written. Some
      simple systems are analyzed in detail to illustrate the applications of the
      theory. Finally, indication is given of possible directions for future
      development of the subject, and of its relationship to existing mathematical
      theories.

PMID- 20057792
TI  - Diffraction images of truncated, one-dimensional, periodic targets.
AB  - Formulas are developed that permit the calculation of the diffraction images of
      truncated, one-dimensional, periodic objects in the presence of incoherent
      illumination using transfer function theory. Special attention is paid to the
      important problem of determining the minimum number of cycles that such a target
      must possess in order for it to act effectively as an infinite periodic target.
      Illustrative calculations are carried out for aberration-free, defocused systems.

PMID- 20057793
TI  - Digital control of focal distances.
AB  - A method is described whereby the focal distance of a lens can be varied
      digitally using electrooptics or other means without changing the magnification
      or spot size. The device is limited to lenses with half-angles less than 15
      degrees . Pairs of polarization switches and passive birefringent elements are
      used. A total of 2(N) equally spaced focal positions can be achieved with N
      switches. If a total length L of birefringent material (indices of refraction n
      and n + Delta(n)) is used, the total shift in focal distance can be as high as
      LDelta(n)/n(2). A ten-stage(1024-position)device falls within the limitations set
      by material and depth-of-field considerations. The shift in focal distance can be
      magnified optically to arbitrary distances, but the image or spot size is also
      magnified in the process.Several practical applications of this device are
      discussed.

PMID- 20057794
TI  - The design of double Gauss systems using digital computers.
AB  - A general study of the design of lenses of double Gauss type and derivatives of
      these has been carried out, with the lenses optimized at an aperture of f/2 and a
      field angle of +/-20 degrees . The results indicate that the number of optimized
      designs is small for all of the constructions that were investigated. Numerical
      examplesfor several designs are given.

PMID- 20057795
TI  - Fiber optics oximeter-densitometer for cardiovascular studies.
AB  - It is now possible to make continuous in vivo measurements of the oxygen
      saturation and total cardiac output of a patient on a real time basis by using
      the recently developed technique of fiber optics spectrophotometry. This paper
      describes instrumental features of a fiber optics oximeter-densitometer which has
      been used on experimental animals as well as on human beings for the measurement
      of oxygen saturation and dye concentration. The in vivo measurement made possible
      with this remote spectrophotometer has shown significant advantages over the in
      vitro method, which in the past has required withdrawal of blood samples and
      subsequent measurements with attendant time delays and inaccuracies. This
      instrument allows the correlation of oxygen saturation variations in various
      regions within the heart with intercardiac, ECG, and pressure measurements. The
      clinical data on this instrument have demonstrated its value in the diagnosis of
      heart defects.

PMID- 20057796
TI  - A telescope suitable for rocket-borne instrumentation.

PMID- 20057798
TI  - Optical and spectral properties of S-20 photocathodes on nesa substrates.

PMID- 20057797
TI  - XUV spectra of a new light source.

PMID- 20057799
TI  - A general relation for D*(lambda(rho)).

PMID- 20057800
TI  - Testing Fabry-Perot iterferometers.

PMID- 20057802
TI  - Narrowband optical heterodyne detection.

PMID- 20057801
TI  - Noise spectra of a liquid He temperature germanium bolometer.

PMID- 20057803
TI  - Laser variable output coupler.

PMID- 20057804
TI  - Rods pumped by flash lamps.

PMID- 20057805
TI  - An optical circulator using quarter-wave plates.

PMID- 20057806
TI  - Diffraction by fiber mosaics.

PMID- 20057807
TI  - Unstable region in the flat-roof resonator.

PMID- 20057808
TI  - Optical computations using a time sharing computer.

PMID- 20057809
TI  - Infrared reflectance and optical constants of tektites.

PMID- 20057811
TI  - Double images in copy holograms.

PMID- 20057810
TI  - Determination of optical constants.

PMID- 20057812
TI  - Torque requirements for a rotating optical chopper.

PMID- 20057813
TI  - Regions of viewability for a pair of intersecting semiinfinite plane mirrors.

PMID- 20057814
TI  - A brief survey of magnetooptics.
AB  - A brief account is given of many of the areas being studied by magnetooptic
      techniques today. The main effort is in solids with the spectrum being broadly
      covered from the uv to the rf region.

PMID- 20057815
TI  - A bibliography of magnetooptics of solids.
AB  - This bibliography contains many of the papers dealing with magnetooptical effects
      in solids. It is arranged in sections by subject matter and in chronological
      order within sections; the papers are alphabetized in each year by first author's
      last name. The information given is author, title of paper, and reference.

PMID- 20057816
TI  - Men and milestones in optics. V: Michael faraday.

PMID- 20057817
TI  - Metric matters.

PMID- 20057818
TI  - Maxwell's Scientific Papers.
AB  - This article is a review of a reprint of the 1890 commemoration edition of The
      Scientific Papers of James Clerk Maxwell (Dover Publications, Inc., New York),
      $12.50. Vol. 1, 607 pp.; Vol.2, 806 pp. One hundred and one of Maxwell's shorter
      papers, articles, speeches, and reviews on electricity and magnetism, the
      dynamical theory of gases, theory of light, color vision and other optical
      problems, elastic solids, molecular physics, etc., are in this reprint; his
      longer treatises on electricity and magnetism, heat, and matter and motion are
      not included. This review is illustrated with photographs from the Maxwell family
      archives which have not been published before.

PMID- 20057819
TI  - Interband magnetooptical studies of semiconductors and semimetals.
AB  - The basic concepts of interband magnetooptical phenomena, involving linear single
      photon absorption and dispersion, are reviewed with particular emphasis on the
      more recent work in semiconductors and also semimetals. Experiments using laser
      sources in linear as well as nonlinear magnetooptical studies are discussed.

PMID- 20057820
TI  - Some continous sources, detectors, linear polarizers, and phase shifters used in
      the spectral regional 0.1-1000 microns.

PMID- 20057821
TI  - Determination of the optical Verdet coefficient in semiconductors and insulators.
AB  - For many applications in research and development, it is of importance to know
      accurately the Verdet coefficients of semiconductors and insulators. The Verdet
      coefficient is defined as the single pass volume Faraday rotation per unit
      magnetic field and unit thickness. By applying the Voigt approximation for
      multiple internal reflections for coherent and incoherent radiation, one can
      determine the Verdet coefficient more accurately. The optical constants of the
      material must be known. The approximation can be applied to single and multiple
      layers of semiconductors or insulators. The advantage of this type of treatment
      is that it can be applied to different energy regions in semiconductors and
      insulators without directly employing a special microscopic model. Measurements
      of interband Faraday rotation in silicon and gallium arsenide, as well as
      measurements of the free carrier Faraday rotation in gallium arsenide and the
      changes in amplitude and phase of the measured rotation in a lead sulfide film on
      a substrate, are discussed.

PMID- 20057822
TI  - Some methods for measuring Faraday rotation.

PMID- 20057823
TI  - Magnetooptical experiments on broad absorption bands in solids.
AB  - The F center is discussed as an example of a point defect in solids with an
      associated broad absorption band. It is shown how the effect of a magnetic field
      on such a center can be studied by means of the Faraday effect with reference to
      the method of moments. The appropriate dispersion relation for obtaining the
      circular dichroism pattern from the Faraday rotation pattern is derived. The
      procedure used to evaluate numerically the dispersion relation is briefly
      described, and results for the F center in KI are compared with a direct
      observation of the effect of a magnetic field on the F band published elsewhere.

PMID- 20057824
TI  - Helicons, magnetoplasma edge, and faraday rotation in solid state plasmas at
      microwave frequencies.
AB  - The effect of magnetic field on propagation of electromagnetic waves through free
      carrier plasmas in semiconductors is discussed. The Faraday configuration and the
      parameter ranges omega(c),omega(p) >> omega and omega(c) >> tau(-1) are
      specifically considered. Dispersion of helicon waves, propagation near the
      magnetoplasma edge (omega(p)(2) = omegaomega(c)), and the Faraday rotation are
      developed in terms of the one-electron Drude theory. Microwave transmission
      measurements at 35 Gc/s on n-type InSb are presented. Experiments near the
      magnetoplasma edge yield the value of the static dielectric constant of the InSb
      lattice K(l) = 19.3 +/- 0.8. Faraday rotation, observed beyond the edge, is found
      to be extremely large. Some practical possibilities for this effect are
      considered.

PMID- 20057825
TI  - Magnetooptical studies of solids using fourier transform spectroscopy.
AB  - An interferometric spectrometer manufactured by the Research and Industrial
      Instruments Company has been adapted for use in polarized far ir magnetooptical
      investigations. The system includes a superconducting magnet and light pipe
      optics. The use of an indium antimonide free electron bolometer and an extrinsic
      germanium photoconductive detector with the system is described. As an example of
      the operation of the spectrometer, some investigations of donor impurity states
      in indium antimonide have been outlined.

PMID- 20057826
TI  - Fourier transform spectroscopy...

PMID- 20057827
TI  - Optical activities in the universities.

PMID- 20057828
TI  - Zeeman discharge tube frequency monitor.
AB  - A discriminant to frequency stabilize a gas laser has been obtained from a
      discharge tube in which the gain profile is split by an ac magnetic field. By
      superimposing a do magnetic field, the discriminant can be centered at any point
      on the gain profile. By employing feedback techniques, the center of the
      discriminant can be used to track a laser frequency; the magnitude of the do
      magnetic field determines the displacement of the laser frequency from the gain
      maximum.

PMID- 20057829
TI  - An automatic recording magnetooptical rotation spectropolarimeter.
AB  - The design and construction of an automatic recording spectropolarimeter for
      measuring magnetooptical rotations (Faraday effect) in a magnetic field is
      described. The instrument has two opposed 5000 G magnetic fields (one for
      solution and one for solvent) to give solute rotation directly as a function of
      wavelength (250-750 mmicro;) to a precision of +/-0.001 degrees in the visible
      and +/-0.003 degrees in the uv region of the spectrum. A description of the
      instrument performance and typical spectra is given.

PMID- 20057830
TI  - Effects of the atmosphere on laser beam propagation.
AB  - An experimental study of horizontal laser beam propagation over paths up to 145
      km long was made in which beam diameter and shape, intensity fluctuations, and
      optical phase distortion were measured. It was found that (1) received beam
      diameter decreases (on-axis power density increases) with increasing transmitter
      aperture to a limit reached at an aperture of about 11 cm, (2) beam diameter
      varies as the 1.2 power of path length, (3) the amplitude of intensity
      fluctuations decreases with increasing receiver aperture and is nearly
      independent of path length for paths longer than 0.55 km, (4) the fluctuation
      spectrum shows a decrease in spectral power with increasing frequency, this
      negative slope becoming steeper with increasing receiver aperture and remaining
      constant with path length, and (5) rms fluctuation in phase path length was
      observed to be 0.25 micro over a 48.8-m path. In addition, it is shown that
      geometrical optics based on the effects of large scale atmospheric irregularities
      does not adequately account for signal intensity fluctuations. These results may
      be helpful in predicting the capability of specific communications systems and in
      understanding better the nature of atmospheric turbulence.

PMID- 20057831
TI  - Water vapor absorption of visible and near infrared radiation.
AB  - Water vapor error function absorption coefficients for visible and near ir
      radiation have been recalculated from experimental transmission data. The error
      function absorption coefficients and the resulting transmissions as a function of
      precipitable water vapor are tabulated for wavelengths from 0.2 micro to 1.3
      micro. Comparisons are made between computed and measured spectral
      transmittances.

PMID- 20057832
TI  - Procedures for attenuated total reflection study of extremely small samples.
AB  - The conditions controlling the sensitivity of ATR toward extremely small samples
      are discussed with a view to their optimization. It is found that the formulas
      developed by Harrick and du Pre for thin film ATR apply to this case, with
      certain modifications. Optimum values for the indices of the optical material,
      sample, and backing, as well as for the incidence angle, are given for light of
      both polarizations. The advantages of reflecting the light beam several times on
      the same sample spot are pointed out, and three optical systems are proposed for
      this. These are a flat trapezoidal ATR plate with slant illumination, a cylinder
      with side-on illumination at an oblique angle to the axis, and a hemisphere
      ridged with retroreflecting teeth, wherein the beam repeatedly strikes the center
      with a rotating incidence plane. Modifications of the latter cell are proposed to
      make its use more convenient, as well as adaptations of its principle for
      conventional reflection, transmission, and ATR fluorescence work.

PMID- 20057833
TI  - Reflective scattering from substrates and evaporated films in the far
      ultraviolet.
AB  - Measurements of radiation reflectively scattered from mirror surfaces have been
      made at the wavelengths 1216 A and 584 A. Several glass and fused silica
      substrates with differing degrees of surface roughness have been studied, as well
      as evaporated films of aluminum and gold as a function of film thickness. A
      relatively small area detector was scanned in angle about the sample, and the
      detected energy integrated over the scattering angle. The results indicate that
      fused silica can be polished to a smoother surface than glass, that a smooth
      substrate is significantly advantageous in obtaining evaporated films having
      surfaces with low scatter, and that gold films are considerably smoother than
      aluminum films of equal thickness.

PMID- 20057834
TI  - Transient solutions to a three level maser.
AB  - The transient behavior of three-level paramagnetic masers is investigated
      theoretically. Exact solutions to three-level maser rate equations are developed
      and their significance discussed. The results indicate the possibility of
      obtaining enhanced maser action at low saturation by pulsed pumping. A new method
      for the measurement of spin-lattice relaxation times for a three-level maser is
      proposed. The method, in addition to certain well-known static measurements,
      requires the observation of the decay of the signal strength when the pumping
      field is switched off.

PMID- 20057835
TI  - Application of the concept of effective refractive index to the measurement of
      thickness distributions of dielectric films.
AB  - In the method to be described, the dielectric film is deposited between two
      silver films so that the threelayer system constitutes a Fabry-Perot interference
      filter. It is shown how measurements of the variation of the wavelength of peak
      transmittance over the surface of the filter can be combined with a measurement
      of the effective refractive index to obtain precise values of the distribution of
      relative geometrical thickness of the dielectric spacing layer.

PMID- 20057836
TI  - Criteria for quantitative schlieren interferometry.
AB  - An evaluation is made of a criterion suggested by Temple for the size and
      location of obstacles in the focal plane of a schlieren interferometer.
      Measurements of the thermal distributions near a heated vertical plate and near a
      heated horizontal cylinder are presented. The results of previous experiments are
      discussed; the results of new experiments are reported. It is concluded that,
      unless the criterion is satisfied, the resulting fringe systems will not give the
      correct quantitative results.

PMID- 20057837
TI  - Diameter optimization for maximum vertical penetration of a beam of collimated
      optical radiation normally incident on the ocean surface.
AB  - The optimum diameter of a circular beam of collimated optical radiation normally
      incident on the ocean surface, in order to obtain a maximum time-average power
      density vertically downward, is determined for (1) the case of a given constant
      beam power density and (2) the case of a given constant total beam power. The
      resulting optima are functions of the roughness of the ocean surface (wind
      velocity), the depth of the point of observation, and the index of refraction.

PMID- 20057838
TI  - Improvement of underwater visibility by reduction of backscatter with a circular
      polarization technique.
AB  - This report presents a brief resume of the underwater visibility problem and
      explains the circular polarization approach for improving contrast. Experimental
      apparatus was set up at the Morris Dam facility of the U.S. Naval Ordnance Test
      Station, Pasadena Annex, and tests were conducted both with and without
      polarization. Results show that use of the polarization technique increased the
      visibility range in turbid water by at least a factor of two.

PMID- 20057839
TI  - Geometrical approach to gaussian beam propagation.
AB  - The curvature of the wavefront and the spot size of a propagating Gaussian beam
      may be determined from simple geometrical transformations of the lateral foci.
      The analysis starts from the construction of the lateral foci in the case of a
      spherical Fabry-Perot. Then the cases of Gaussian beam propagation through media
      with different refractive indices, lenses, and simple optical systems are
      treated. Constructions show how propagation in the image space is readily
      determined in each case. This analysis is the generalization of the technique
      outlined by Deschamps and Mast. The geometrical constructions developed for
      simple cases are applied to the design of some special cases of interest in laser
      optics: cavities by a lens, laser zoom telescope, and ring cavity.

PMID- 20057840
TI  - A 5-m integrating sphere.
AB  - An integrating sphere with an inner diameter of 5 m was constructed with special
      attention in order to make a true sphere by welding together steel plates of
      thickness of 12 mm. The deviations of radii from a true sphere are within +/
      0.3%. A special lift, which is installed below the sphere, is used for changing a
      lamp or painting the sphere. The inner surface of the sphere was coated with a
      water paint of BaSO(4). Its spectral reflectance was measured by a method, in
      which a part of the spherical surface was substituted by a surface with low
      reflectance and spectrophotometric measurements were made on the luminance of the
      measurement window of the sphere before and after the substitution, operating a
      tungsten lamp in the sphere. The values of spectral reflectance obtained by this
      method were from 0.93 to 0.96 in the visible region, ten months after the
      coating.

PMID- 20057841
TI  - A new derivation of third-order aberration coefficients.
AB  - The Feder expressions for four third-order aberration coefficients, namely, B for
      spherical aberration, F for coma, C for astigmatism, E for distortion, and the
      Petzval curvature P, are derived by a new and direct method based on the
      wavefront concept and with the use of rather elementary means of geometry and
      algebra. Their relation with the wavefront aberration coefficients is given.

PMID- 20057842
TI  - A rotating polarizer for faraday rotation measurements.

PMID- 20057844
TI  - Measured internal losses and output energies of neodymium glass lasers.

PMID- 20057843
TI  - Astigmatism in the Mach-Zehnder interferometer.

PMID- 20057845
TI  - Absorption spectra apparatus using optical correlation for the detection of trace
      amounts of SO(2).

PMID- 20057846
TI  - Clamped electrooptic coefficients of KDP and quartz.

PMID- 20057848
TI  - A new type of astronomical telescope with an extra large aperture.

PMID- 20057847
TI  - Comments on optical characteristics of a proposed reflectance standard.

PMID- 20057849
TI  - Optical peregrinations in the Netherlands.
AB  - Optics in The Netherlands dates back to the origin of the telescope. The names of
      Lippershey, Snell Huygens, and van Leeuwenhoek typify this early dominance of the
      Dutch in optics. Peregrinations to a variety of museums, laboratories, and
      universities places their efforts in perspective to the current activity
      described in this issue.

PMID- 20057850
TI  - An illustration.

PMID- 20057851
TI  - The rapid and precise determination of the optical thickness of thin coatings in
      a vacuum.
AB  - The classical interference experiment with a double slit is adapted for measuring
      the optical thickness (n - 1)d of transparent and slightly absorbing thin films
      on transparent or reflecting substrates and for measuring the geometrical
      thickness d of metal films on reflecting substrates. Also, a method is described
      for measuring in vacuum the optical thickness of transparent or slightly
      absorbing thin films on transparent substrates. Results are given of measurements
      on magnesium fluoride, silicon monoxide, and zinc sulfide films. The influence of
      admitting air into the vacuum chamber has been investigated. With the available
      arrangements, a precision of lambda/1000 in the determination of the optical or
      geometrical thickness is easily obtainable for all film thicknesses. A thickness
      determination can he completed in about 1 min.

PMID- 20057852
TI  - Abraham Cornelis Sebastiaan van Heel.

PMID- 20057853
TI  - Lens and surface testing with compact interferometers.
AB  - Easily manufacturable components are assembled into compact modified Twyman-Green
      interferometers and an interference microscope with only one objective.

PMID- 20057854
TI  - A rapid precision wavelength measuring apparatus.
AB  - An apparatus is described that determines automatically the significant
      information of spectral plates. First the plate transmission is measured step by
      step along the spectrum, digitized, and stored on paper tape. This is processed
      by means of a computer programmed to find line positions and intensities and to
      calculate wavelengths and wavenumbers. The final wavelength precision as tested
      by means of thorium standard lines is of the order of a few 0.001 A for a
      reciprocal dispersion of 0.9 A/mm.

PMID- 20057855
TI  - Applied optics of optics and opticists.

PMID- 20057856
TI  - Development of a ring laser for polarimetric measurements.
AB  - In this paper a method for the measurement of small optical rotations by using a
      ring laser of special design is described. The proposed instrument could be used,
      for example, to measure small optical rotations in the near ir, caused by
      vibration bands of organic substances. The development of the ring laser is
      discussed. A general theory concerning the states of polarization of a laser with
      an anisotropic cavity is presented. The dynamic behavior of the state of
      polarization, as a function of an axial magnetic field, in cavities with linear
      and circular anisotropies is analyzed. This analysis has led to two methods of
      polarimetric measurements, which are discussed in detail. The experimental setup
      is given.

PMID- 20057857
TI  - Optical path-length difference effects in photomixing with multimode gas laser
      radiation.
AB  - It has been widely observed that when a multimode gas laser is employed in
      photomixing experiments, the heterodyne signal amplitude depends on the optical
      path length difference between the paths traversed by the two light beams. In
      this paper, a simple phenomenological model of multimode gas laser radiation is
      used to calculate the dependence of the heterodyne signal amplitude on optical
      path length difference for various numbers of oscillating axial modes in a
      multimode gas laser. The results have important implications for the design of
      optical heterodyne receivers.

PMID- 20057858
TI  - Interferometry of resonator modes in submillimeter wave lasers.
AB  - Submillimeter wave gas lasers are characterized by low Fresnel numbers and by
      gain widths smaller than the mode separations. This allows interferometry of
      laser emissions and resonator modes with the aid of the laser resonator. The
      theory of Bergstein and Schachter on modes occurring in resonators with low
      Fresnel numbers is compared with the experimental data obtained by laser
      resonator interferometry. The influence of the tilt of a resonator mirror on the
      intensity of the laser emission is measured for different modes.

PMID- 20057859
TI  - Light scattering by laser mirrors.
AB  - The Beckmann theory of scattering is applied to laser mirrors. It is shown that
      the theory correctly predicts the wavelength dependence of scattering profiles.
      The theory can be used to obtain numbers (sigma and Tau) for a laser mirror which
      describe its scattering characteristics. Scattering measurements made on eleven
      laser mirrors are presented.

PMID- 20057860
TI  - Some factors affecting the pumping efficiency of optically pumped lasers.
AB  - As a preliminary to the calculation and discussion of pumping efficiency, the
      results of an investigation into the properties of xenon flash tubes are given.
      Time resolved spectroscopy showed that the radiation during the flash is
      essentially that of a blackbody. The small range of measured blackbody
      temperatures (6000 degrees K to 7000 degrees K) cannot account for the variation
      in radiated power during the flash. However, emissivity variations (deduced from
      published absorption data) explain the observed time dependence exactly. An ionic
      mechanism is outlined which explains the spectral distribution of the radiation,
      the electrical properties of the discharge, and the emissivity variations.
      Possible reasons for the low radiative efficiency of 28% during the flash are
      discussed. The fraction of the electrical energy supplied to the tube reaching
      the laser crystal is calculated, taking into account the cavity geometry and wall
      reflectivity, the flash tube radiative efficiency and spectral distribution, the
      crystal ze and sorption, and the partial reconversion by the flash tube of light
      not absorbed in the crystal which returns to the tube. The predicted laser
      oscillation threshold agrees well with experiment. It is concluded that, while
      reconversion can significantly increase the effective radiative efficiency of the
      tube, the over-all efficiency of the laser is still limited by the low intrinsic
      radiative efficiency. Numerical examples are given to show that this parameter
      exercises the biggest influence on the present pumping efficiencies of about
      0.5%. Over-all efficiencies of up to 9% could be obtained if this radiative
      efficiency could be raised to about 90%. Success in this area could give greater
      benefits than attempts to improve the spectral distribution of the tube
      radiation.

PMID- 20057861
TI  - Transverse mode structure in unstable optical cavities.
AB  - The characteristics of unstable optical cavities have been investigated
      experimentally using a pulsed argon laser. We have studied the amplitude and
      phase distribution in the transverse modes of unstable cavities, as well as the
      characteristics of the output beam. Our experimental results are in qualitative
      agreement with existing theory. We have also demonstrated that an unstable cavity
      can be used to provide variable output coupling for a laser.

PMID- 20057862
TI  - Recording parameters of spatially modulated coherent wavefronts.
AB  - Various parameters of recording spatially modulated coherent light have been
      studied, with particular emphasis on the parameters related to constructing
      holograms. These include the ratio of the reference beam's intensity to that of
      the signal beam, the offset angle, the film's transfer characteristic, and the
      recording wavelength. Experimental results were obtained by recording
      interference patterns on highresolution film using the 6328-a line of the He-Ne
      laser. The bias level of the interference pattern was varied so as to vary the
      operating point on the curve representing the film's amplitude transmittance vs
      exposure characteristics. The percent modulation and the spatial frequency were
      also varied at each of the operating points. Interference patterns were recorded,
      using the 4880-aand 5145-a lines from the argon laser. From these data, the
      optimum bias level and the ratio of the signal beam to the reference beam for
      recording interference patterns are determined. The modulation transfer function
      of the film can also be determined.

PMID- 20057863
TI  - Temporal filtering properties of holograms.
AB  - A hologram may be regarded as a linear temporal filter operating on the time
      varying object fields incident during exposure. Such a point of view allows the
      effects of object vibrations and other simple motions to be predicted in a
      straightforward fashion. In addition, this filtering property suggests that
      holograms might be used to provide doppler maps of moving objects. Finally, the
      temporal-filtering viewpoint offers insight into the effect of the wavefront
      reconstruction process on images of noncoherent objects.

PMID- 20057864
TI  - Optical resonators in the unstable region.
AB  - The spectrum of characteristic oscillation frequencies and modal losses for
      spherical mirror opticalresonators is derived in an approximation equivalent to
      geometrical optics. This is a significant approximation for unstable or high loss
      configurations when the Fresnel number is large. The analysis is based on the
      scalar integral equations of Fox and Li and agrees with the known result for the
      dominant mode losses in the geometrical optics limit.

PMID- 20057865
TI  - Dihedral optical resonators and prism beam waveguides.
AB  - A simple theory is developed for optical resonators, in which the mirrors are
      each composed of two planes forming a nearly straight dihedral angle and an
      equivalent beam-waveguide comprising a sequence of narrow angle prisms. Geometric
      optical considerations yield the variation of the intensity within the resonator
      in a manner analogous to (although not entirely as satisfying as in) the case of
      the spherical mirror resonator. Modes of the continuous medium, identified as the
      limit of particular sequences of closely spaced weak prisms, characterized by a
      parameter Omega, are found in terms of Airy functions. An appropriate spot size
      parameter is given by [Omega/2k0(2)]1/3, where k(0) is the wavenumber.

PMID- 20057866
TI  - Improvement of the degree of spatial coherence in a Michelson interferometer.
AB  - The visibility of fringes of equal thickness of an approximately plane parallel
      plate illuminated by a quasi-monochromatic primary source is expressed in terms
      of the degree of longitudinal spatial coherence, i.e., the coherence of two
      points lying on a normal to the source. Use of polarization interferometers to
      increase the degree of coherence is discussed. This permits the use of a large
      source in a Michelson interferometer even when its two armlengths differ
      significantly.

PMID- 20057867
TI  - Spectrometer system for studying absorption from excited metastable states of
      ions in crystals.
AB  - A spectrometer system for studying excited state absorption of ions in crystals
      is described. Pulsed xenon short arc lamps and keyed photomultipliers are used to
      measure the transmission after optically pumping the ions into an excited state.
      A wide dynamic range of absorption coefficients of excited states with lifetimes
      down to less than 100 microsec can be measured. A repeatability near the shot
      noise limit is obtained.

PMID- 20057869
TI  - A streak spectrograph with microsecond resolution.
AB  - An inexpensive, time-resolved spectrograph with microsecond time resolution has
      been simply constructed in the laboratory. A Gaertner glass-prism monochromator
      with a flat focal plane was combined with a Beckman-Whitley drum camera with the
      lens removed. The resulting combination has a geometric aperture of f/10 with a
      wavelength resolution of 1 A at 4300 A. The wavelength range of 3900 A to 9000 A
      can be covered with three settings of the wavelength drum on the monochromator.
      Examples of the spectral time history of reflected shocks in nitrogen and in
      oxygen for the conventional shock tube are given. This instrument has been
      particularly useful in recording Stark-broadened hydrogen lines and oxygen lines
      to measure the ion density in shock-heated gas samples. A continuum brightness of
      4.3 x 10(7) ergs sec(-1) cm(-2) sr(-1) (10 A)(-1) at 4300 A is required to
      produce a plate density f 0.3 on I-F film for optimum entrance slit width and 2.5
      microsec exposure time.

PMID- 20057870
TI  - Synchronized high speed scanning infrared spectrometer.
AB  - A spectrometer which scans a wavelength band of 0.6 micro in 30 microsec and is
      useful from 2-6 micro is described. The instrument can be synchronized with a
      pulsed source with a minimum triggering delay of 15microsec. The instrument is
      basically an Ebert spectrometer equipped with an indium antimonide detector at
      the exit slit, an aluminum scanning mirror placed 5 cm before the exit slit, and
      a wavelength calibration signal generator. The scanning mirror, which is
      supported on pivots inside a helical coil, deflects the spectrum through an angle
      of approximately 90 degrees onto the exit slit. When a capacitor is discharged
      through the coil, the resulting magnetic field spins the aluminum mirror causing
      the spectrum to move across the exit slit. The wavelength calibration signal
      generator produces a series of electrical pulses as the scanning mirror turns,
      permitting wavelength calibration when the pulses are displayed below the
      spectrometer signal on a dual beam oscilloscope. Using this instrument on a shock
      tube, data have bee obtained on the absolute spectral radiation intensity of air,
      nitrogen, neon, and argon heated by reflected shocks to equilibrium temperatures
      in the range of 6000 degrees K to 10,000 degrees K. In this temperature region
      with these gases, an important source of continuum radiation is neutral
      Bremsstrahlung caused by the inelastic scattering of electrons from neutral atoms
      and molecules. By employing the scanning ir spectrometer it has been possible to
      separate the continuum radiation from contributions owing to lines and bands and
      determine the cross section for the neutral Bremsstrahlung.

PMID- 20057871
TI  - Far infrared bandpass filters and measurements on a reciprocal grid.
AB  - Transmittance and reflectance measurements on wirecloth and electroformed
      metallic meshes are presented in the region 0.01 <or= lambda/d <or= 5. The
      results were obtained under equal geometric optical conditions with a vacuum
      grating spectrometer. The measurements are used for the construction of a
      transmission bandpass filter in the wavenumber region nu > 18 cm(-1). In order to
      be able to construct a bandpass filter in the entire far ir, a reciprocal grid is
      investigated and found to be suitable as a transmission low pass filter
      characterized only by geometrical parameters.

PMID- 20057872
TI  - Optical tunneling and its applications to optical filters.
AB  - Several applications of optical tunneling (frustrated total reflection) are
      briefly discussed. There are several classes of optical bandpass filters which
      use optical tunneling: the Fabry-Perot filter (alias the FTR filter), the single
      tunnel layer filter, and the multiple tunnel layer filter. The properties of
      these filters are examined. The multiple tunnel layer filter shows promise as an
      ir long-wave pass filter.

PMID- 20057873
TI  - An image-scanning three-beam photoelectric photometer for astronomical
      observations.
AB  - A high-speed focal-plane image scanning system is described. With such a system
      an astronomical image can be linearly scanned without moving either telescope or
      detector, and without defocusing. The application of the scanning system, used in
      conjunction with a three-beam photoelectric photometer, to lunar research is
      discussed briefly.

PMID- 20057874
TI  - Remote sensing of surface and cloud temperatures using the 899-cm interval.
AB  - The spectral interval centered at 899 cm(-1) with a bandpass of 8.75 cm(-1) is
      used for the measurements of surface and cloud-top temperatures from an altitude
      of 30 km. The continuum and selective absorption contribution to such
      measurements are discussed. The observations were obtained, using a balloon
      flight spectrometer, on two occasions: once from Palestine, Texas, in a tropical
      humid air mass, and once from Sioux Falls, South Dakota, in a cold arctic air
      mass. The results from these observations are compared with the screen
      temperatures under the balloon and with special surface temperature measurements
      made using a thermistor and a radiometer.

PMID- 20057875
TI  - Measurement of total hemispherical emittance of transparent materials at low
      temperature.
AB  - A transient calorimetric method of measuring the total hemispherical emittance of
      transparent materials in the temperature range 75 degrees K to 312 degrees K is
      described. Measured emittance values with an estimated accuracy of +/-5% are
      presented forvarious thicknesses of NaCl and fused quartz. The emittance of NaCl
      decreased from 0.67 at 75 degrees K to 0.34 at 312 degrees K. The emittance of
      quartz was approximately constant at 0.73 over the same temperature range.
      Increasing the thickness of NaCl resulted in slight increases in emittance; no
      thickness effect was observed in the quartz. Total normal emissivity values
      calculated for NaCl from optical constants were not appreciably different from
      the measured total hemispherical emittances.

PMID- 20057876
TI  - The measurement of infrared dispersion in solids by a method based on small
      particle scattering.
AB  - A method of measuring the components of the complex index of refraction of solids
      near the reststrahlen region is described. The method is based on the scattering
      of electromagnetic radiation by small particles, and it is applied here to the
      cases MgO, LiNbO(3), CdF(2), and PbF(2).

PMID- 20057877
TI  - A comparison of computed and experimental spectral transmissions through haze.
AB  - Spectral transmissions through haze are computed using meteorological
      observations to specify aerosol scattering and water vapor, carbon dioxide, and
      ozone absorption. The computed spectral transmissions are compared with the
      appropriate experimental transmissions to evaluate the degree to which a natural
      spectral transmission can be simulated by a computed spectral transmission. The
      comparison indicates that the dominant atmospheric attenuating parameter is the
      absolute distribution of aerosols.

PMID- 20057878
TI  - On the saturation luminance of high density microsecond arc channels.
AB  - The emission of high current microsecond arc channels in argon and helium, with a
      1-mm gap is studied by means of a 20-nsec exposure Kerr cell shutter, and
      profiles of the relative luminance B are determined from the photographic arc
      image. This method is largely unaffected by instabilities in the arc position;
      the scatter of relative luminance values was smaller than +/- 5%. Maximum values
      of the saturation luminance B in the axis of the arc channel are observed over a
      wide range of arc current which is altered by the gas pressure. A ratio of
      B(He)/B(A) = 1.52 for the two gases is determined. The luminance profile across
      the arc channel demonstrates increasing opacity after saturation is reached.

PMID- 20057879
TI  - Acoustical resonances in modulated xenon and krypton compact arc lamps.
AB  - When the dc current through a compact arc lamp is modulated, are instabilities
      appear at discrete frequencies. At some of these frequencies, the instabilities
      are sufficiently severe to extinguish the lamp. The primary frequency at which
      the arc bows to the side and tends to extinguish has been studied as a function
      of bulb diameter and current for xenon and krypton lamps. A theoretical treatment
      of acoustical resonances is presented and it is quantitatively shown that the
      experimentally determined primary extinction frequency coincides with the primary
      acoustical resonance. Furthermore, the dependence of the primary extinction
      frequency on bulb diameter, temperature, pressure, and molecular weight fit the
      acoustical resonance theory.

PMID- 20057880
TI  - Development method and modulation transfer function of xerography.
AB  - Based on earlier publications it is shown that the theory of the modulation
      transfer function (MTF) may be applied to the vertical component of the
      electrostatic field. Whether the theory may be applied to the visible xerographic
      reproduction depends on the development method which also has an effect on the
      curve shape of the MTF. The MTF may be applied to pictorial reproductions but not
      to line copy with strong adjacency effect.

PMID- 20057881
TI  - An analysis of saturable absorbers.
AB  - This paper contains an analysis of the behavior of saturable filters, based on
      models with simple energy level structures. In this analysis, the effects of
      possible excited state absorption at the irradiating wavelength are considered
      and are shown to give rise to a nonsaturable component of the absorption
      coefficient. Expressions for the steady-state transmission of an optically thick
      saturable absorber, and for the temporal response of an optically thin absorber,
      are derived. The question of homogeneous vs inhomogeneous broadening of the
      absorption line is discussed, and it is suggested that spectral hole burning may
      occur in a thermally broadened line at a sufficiently high irradiance level. The
      desirable features of a saturable absorber for use in a Q-switched laser system
      are briefly described, and it is shown how the usual rate equations for a laser
      system may be amended to include the effects of an intracavity saturable filter.

PMID- 20057882
TI  - OSA research and education.

PMID- 20057883
TI  - Optical material problems of interplanetary space.
AB  - The successful flights of Mariners II and IV demonstrated that optical systems
      can survive and operate after months of exposure to interplanetary space. Special
      considerations must be taken in designing for deep space. The phenomena of
      sublimation and deterioration of solid materials in deep-space vacuum influence
      the selection of all materials used in the optical system including metals and
      organic compounds. Three basically different approaches of thermal design are
      available to the designer. Each method is capable of maintaining focus throughout
      large temperature excursions. Micrometeoroid and radiation damage are not major
      problems. The material selection for and thermal design of the Mariner IV
      television camera optical system is described.

PMID- 20057884
TI  - Collor-corrected Mangin mirror.
AB  - Extension of the principle of the Mangin mirror to a color-corrected version
      yields designs superior to the equivalent paraboloid. This is true theoretically
      with regard to coma correction and practically with regard to ease of
      fabrication, particularly for high relative apertures. Examples are given of
      designs with low secondary spectrum and one with zero third-order coma.

PMID- 20057885
TI  - Semiautomatic generation of optical prototypes.
AB  - This paper presents the theory and application of a computer approach to the
      problem of finding lens prototypes from given sets of design goals. The procedure
      is based on the yy method of Delano and has two independent segments: a strictly
      first-order phase and a combined first- and third-order phase. The former
      optimizes the first-order layout with respect to geometrical and optical
      constraints. In this phase the independent variables are the paraxial marginal
      and principal ray heights. The starting point is a set of yy coordinates which
      may be either generated by the computer program or supplied by the designer. The
      second phase combines third-order information with the constraints of the first
      phase. Here it is more convenient to use ray angles as independent variables. The
      optimization scheme for both phases is an orthogonal method which has been used
      successfully on a variety of optical problems.

PMID- 20057886
TI  - A 50.83-cm focal length, f/1 catadioptric objective.
AB  - A catadioptric objective system of the Flugge type has been developed for
      experimental use by the U.S. Army. Major features of this objective are its large
      aperture and EFL [both 50.8 cm (20 in.)], its compact package configuration in
      spite of these dimensions, and the high image quality achieved with a simple
      three component system over a 2.8 degrees field of view. In this paper, the
      optical and mechanical designs of the objective are described, and some results
      of laboratory tests of a prototype lens are presented.

PMID- 20057887
TI  - Schmidt-Cassegrain telescope system with a flat field: II.

PMID- 20057888
TI  - Making a high efficiency antihalation backing for photographic plates which
      eliminates interference bands produced by coherent light.

PMID- 20057889
TI  - Heavily doped silicon as a low temperature transmission filter for the far
      infrared.

PMID- 20057890
TI  - Properties of photomultipliers.

PMID- 20057891
TI  - On a convergence correction for dispersive Fourier spectrometry.

PMID- 20057892
TI  - An example of the application of pulsed light holography to aerodynamics.

PMID- 20057893
TI  - Update on the management of attention-deficit/hyperactivity disorder in children
      and adults: patient considerations and the role of lisdexamfetamine.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder
      characterized by atypical levels of inattention, hyperactivity, and impulsivity
      that impair daily living activities. Although commonly associated with children
      and adolescents, current literature and practice now demonstrate the impairment
      the disorder may impose on adults as well. Central nervous system (CNS) stimulant
      medications are the first-line therapy for ADHD. CNS stimulants include
      methylphenidate and amphetamine derivatives. Longer-acting formulations used once
      daily are often preferred to avoid medication administration during school or
      work as well as to avoid side effects associated with rapid fluctuations in serum
      concentrations associated with multiple daily dosing. Lisdexamfetamine, a new,
      novel amphetamine product, has been shown to provide efficacy upwards of 12 hours
      in children and adults with a side effect profile similar to those of other
      longer-acting amphetamine products. Owing to its unique prodrug composition and
      the need for oral administration to activate the medication, lisdexamfetamine may
      offer advantages in clinical situations where stimulant abuse is a concern.

PMID- 20057894
TI  - Monitored anesthesia care (MAC) sedation: clinical utility of fospropofol.
AB  - Fospropofol, a phosphorylated prodrug version of the popular induction agent
      propofol, is hydrolyzed in vivo to release active propofol, formaldehyde, and
      phosphate. Pharmacodynamic studies show fospropofol provides clinically useful
      sedation and EEG/bispectral index suppression while causing significantly less
      respiratory depression than propofol. Pain at the injection site, a common
      complaint with propofol, was not reported with fospropofol; the major patient
      complaint was transitory perianal itching during the drug's administration.
      Although many clinicians believe fospropofol can safely be given by a registered
      nurse, the FDA mandated that fospropofol, like propofol, must be used only in the
      presence of a trained anesthesia provider.

PMID- 20057895
TI  - In-hospital resuscitation: opioids and other factors influencing survival.
AB  - PURPOSE: "Code Blue" is a standard term used to alertt hospital staff that a
      patient requires resuscitation. This study determined rates of survival from Code
      Blue events and the role of opioids and other factors on survival. METHODS: Data
      derived from medical records and the Code Blue and Pharmacy databases were
      analyzed for factors affecting survival. RESULTS: During 2006, rates of survival
      from the code only and to discharge were 25.9% and 26.4%, respectively, for Code
      Blue events involving cardiopulmonary resuscitation (CPR; N = 216). Survival
      rates for events not ultimately requiring CPR (N = 77) were higher, with 32.5%
      surviving the code only and 62.3% surviving to discharge. For CPR events, rates
      of survival to discharge correlated inversely with time to chest compressions and
      defibrillation, precipitating event, need for airway management, location and
      age. Time of week, witnessing, postoperative status, gender and opioid use did
      not influence survival rates. For non-CPR events, opioid use was associated with
      decreased survival. Survival rates were lowest for patients receiving continuous
      infusions (P < 0.01) or iv boluses of opioids (P < 0.05). CONCLUSIONS: One
      quarter of patients survive to discharge after a CPR Code Blue event and two
      thirds survive to discharge after a non-CPR event. Opioids may influence survival
      from non-CPR events.

PMID- 20057896
TI  - The JUPITER and AURORA clinical trials for rosuvastatin in special primary
      prevention populations: perspectives, outcomes, and consequences.
AB  - Statins have emerged at the forefront of preventive cardiology and have
      significantly reduced cardiovascular events and mortality. Nonetheless,
      cardiovascular disease remains the leading cause of death in the United States
      and in other developed countries, as well as the etiology of significant
      morbidity and health-care expenditure. In an attempt to reduce potentially missed
      opportunities for instituting preventive therapy, the JUPITER study
      (Justification for the Use of Statins in Prevention: an Intervention Trial
      Evaluating Rosuvastatin) and the AURORA study (A Study to Evaluate the Use of
      Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and
      Cardiovascular Events) examined the effect of statins in two specific patient
      populations who currently do not meet the guidelines for statin treatment, but
      nonetheless, are at high cardiovascular risk. This review outlines the JUPITER
      and AURORA trials, interprets the data and significance of the results, analyses
      the drawbacks and impact of both trials and delineates the potential for further
      clinical trials.

PMID- 20057897
TI  - Management of hypertension with fixed dose combinations of candesartan cilexetil
      and hydrochlorothiazide: patient perspectives and clinical utility.
AB  - Hypertension treatment and control is largely unsatisfactory when guideline
      defined blood pressure goal achievement and maintenance are considered. Patient-
      and physician-related factors leading to non-adherence interfere in this respect
      with the efficacy, tolerability, and convenient use of pharmacological treatment
      options. Blockers of the renin-angiotensin system (RAS) are an important
      component of antihypertensive combination therapy. Thiazide-type diuretics are
      usually added to increase the blood pressure lowering efficacy. Fixed drug-drug
      combinations of both principles like candesartan/hydrochlorothiazide (HCTZ) are
      highly effective in lowering blood pressure while providing improved compliance,
      a good tolerability, and largely neutral metabolic profile. Comparative studies
      with losartan/HCTZ have consistently shown a higher clinical efficacy with the
      candesartan/HCTZ combination. Data on the reduction of cardiovascular endpoints
      with fixed dose combinations of antihypertensive drugs are however scarce, as are
      the data for candesartan/HCTZ. But many trials have tested candesartan versus a
      non-RAS blocking comparator based on a standard therapy including thiazide
      diuretics. The indications tested were heart failure and stroke and particular
      emphasis was put on elderly patients or those with diabetes. In patients with
      heart failure, for example, the fixed dose combination might be applied in
      patients in whom individual titration resulted in a dose of 32 mg candesartan and
      25 mg HCTZ which can then be combined into one tablet to increase compliance with
      treatment. Also in patients with stroke the fixed dose combination might be used
      in patients in whom maintenance therapy with both components is considered. Taken
      together candesartan/HCTZ assist both physicians and patients in achieving long
      term blood pressure goal achievement and maintenance.

PMID- 20057898
TI  - Persistent high fever and systemic inflammation induced by percutaneous coronary
      intervention-related periaortitis.
AB  - After coronary catheterization, fever sometimes occurs, usually transiently. We
      report a very rare case that suggests persistent high fever and systemic
      inflammation might be caused by periaortitis induced by coronary catheterization
      including percutaneous coronary intervention.

PMID- 20057899
TI  - Early cardiovascular abnormalities in newly diagnosed obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is associated with high cardiovascular morbidity
      and mortality. Recent studies have shown that it is associated with
      atherosclerosis and left ventricular dysfunction markers. The aim of this study
      was to assess the cardiovascular effects of OSA depending on its severity, in
      patients without clinically diagnosed cardiovascular disease. One hundred thirty
      newly diagnosed, nondiabetic OSA patients (mean age 49 +/- 10 years), without
      vasoactive treatment were included. They underwent clinical and ambulatory blood
      pressure measurements, echocardiography, carotid ultrasound examination, and a
      carotid-femoral pulse wave velocity (PWV) measurement. Seventy-five percent of
      the subjects were hypertensive according to the clinical or ambulatory
      measurement. More patients with the most severe forms (respiratory disturbance
      index >37/hour) had a nondipper profile (52% vs 34%; P = 0.025) and their left
      ventricular mass was higher (40 +/- 7 vs 36 +/- 8 g/m, p = 0.014). This last
      parameter was independently and inversely associated with mean nocturnal oxygen
      saturation (P = 0.004). PWV and carotid intima-media thickness did not differ
      between one OSA severity group to another, but the prevalence of carotid
      hypertrophy was higher when mean SaO(2) was below 93.5% (29.5 vs 16%; P = 0.05).
      Our study shows that in OSA patients without clinically diagnosed cardiovascular
      disease, there is a significant left ventricular and arterial effect, which is
      even more marked when OSA is severe.

PMID- 20057901
TI  - Update on the everolimus-eluting coronary stent system: results and implications
      from the SPIRIT clinical trial program.
AB  - Drug-eluting stents (DES) have had a major impact in interventional cardiology.
      Compared to bare metal stents, they significantly reduce restenosis and the need
      for target vessel revascularization. Four DES are available in the US, the first
      generation sirolimus-eluting (Cypher((R))) and paclitaxel-eluting (Taxus((R)))
      stents and later approved second-generation everolimus-eluting (Xience V((R)))
      and zotarolimus-eluting (Endeavor((R))) stents. The Xience V stent was approved
      on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT
      clinical trial program. Within this trial series, the Xience V was superior to
      its bare metal stent counterpart, the Vision(R) stent, and noninferior to the
      paclitaxel-eluting stent for target vessel failure at 9 months. This review
      provides a comprehensive assessment of the data derived from both the pre- and
      post-approval randomized controlled trials and registry studies of Xience V that
      comprise the SPIRIT clinical trial program including recently published mid-term
      outcomes. The implications of the results in terms of interventional practice
      will be discussed.

PMID- 20057900
TI  - Nitric oxide and coronary vascular endothelium adaptations in hypertension.
AB  - This review highlights a number of nitric oxide (NO)-related mechanisms that
      contribute to coronary vascular function and that are likely affected by
      hypertension and thus become important clinically as potential considerations in
      prevention, diagnosis, and treatment of coronary complications of hypertension.
      Coronary vascular resistance is elevated in hypertension in part due to impaired
      endothelium-dependent function of coronary arteries. Several lines of evidence
      suggest that other NO synthase isoforms and dilators other than NO may compensate
      for impairments in endothelial NO synthase (eNOS) to protect coronary artery
      function, and that NO-dependent function of coronary blood vessels depends on the
      position of the vessel in the vascular tree. Adaptations in NOS isoforms in the
      coronary circulation to hypertension are not well described so the compensatory
      relationship between these and eNOS in hypertensive vessels is not clear. It is
      important to understand potential functional consequences of these adaptations as
      they will impact the efficacy of treatments designed to control hypertension and
      coronary vascular disease. Polymorphisms of the eNOS gene result in significant
      associations with incidence of hypertension, although mechanistic details linking
      the polymorphisms with alterations in coronary vasomotor responses and
      adaptations to hypertension are not established. This understanding should be
      developed in order to better predict those individuals at the highest risk for
      coronary vascular complications of hypertension. Greater endothelium-dependent
      dilation observed in female coronary arteries is likely related to endothelial
      Ca(2+) control and eNOS expression and activity. In hypertension models, the
      coronary vasculature has not been studied extensively to establish mechanisms for
      sex differences in NO-dependent function. Genomic and nongenomic effects of
      estrogen on eNOS and direct and indirect antioxidant activities of estrogen are
      discussed as potential mechanisms of interest in coronary circulation that could
      have implications for sex- and estrogen status-dependent therapy for hypertension
      and coronary dysfunction. The current review identifies some important basic
      knowledge gaps and speculates on the potential clinical relevance of hypertension
      adaptations in factors regulating coronary NO function.

PMID- 20057902
TI  - Smoking, an additional risk factor in elder women with primary open-angle
      glaucoma.
AB  - PURPOSE: Smoking is a serious public health problem worldwide. Some authors refer
      to it as the "silent epidemic of the 20th century." It constitutes an important
      risk factor for ocular pathologies such as age-related macular degeneration
      (ARMD), diabetic retinopathy, and neuropathy because the toxic effects of tobacco
      play a key role in the deterioration of eye tissue. Damage to trabecular meshwork
      cells (TMC) and retinal ganglion cells (RGC), involving inflammation and
      apoptosis mechanisms, has been proved in glaucoma. The aim of this study was to
      determine whether smoking influences the progression of primary open angle
      glaucoma (POAG) in women. METHODS: This experimental study involved a sampling of
      consecutive cases of smokers, ex-smokers and non-smokers women with POAG. One
      hundred and twenty women with POAG, aged 40-90 years, were enrolled (40 smokers,
      40 ex-smokers and 40 non-smokers). Samples of aqueous humor (AH) and plasma from
      each subject were obtained at the beginning of the surgical procedures. Both
      inflammation and apoptosis processes in the subjects were studied by means of
      enzyme immunoassay and western blot procedures respectively. We analyzed the
      interleukin-6 (IL-6) levels as an inflammation marker and the expression of
      caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1) as apoptosis markers.
      RESULTS: IL-6, caspase-3, and PARP-1 levels were significantly higher in the
      smoker women who smoked than in the ex-smoker and non-smoker glaucomatous groups
      of the same gender (p<0,05). CONCLUSIONS: Inflammation and apoptosis marker
      levels increase with smoking in the aqueous humor and plasma samples of POAG
      women. Smoking could be an important additional risk factor for glaucoma
      progression in elderly women.

PMID- 20057903
TI  - Functional and clinical data of Best vitelliform macular dystrophy patients with
      mutations in the BEST1 gene.
AB  - PURPOSE: To analyze functional and clinical data of Best vitelliform macular
      dystrophy (VMD) patients with mutations in the BEST1 gene. METHODS: Best VMD
      patients with BEST1 mutations were evaluated prospectively regarding age, age of
      onset, best-corrected visual acuity (BCVA), fundus autofluorescence, fluorescein
      angiography, optical coherence tomography, and electro-oculography. Mutations in
      BEST1 were established by direct sequencing. RESULTS: Forty-six eyes of 23
      patients (10 male, 13 female) were included in the study. We identified nine
      different BEST1 mutations (3/9 novel), in ten unrelated families. The age of
      patients ranged between 3 and 75 years; age of onset varied between 2 and 67
      years. BCVA ranged between 20/20 and 20/200. On the basis of fundus biomicroscopy
      with direct illumination, using one widely accepted classification, the macular
      lesions could be counted as follows: 1. no lesion (normal fovea): eight eyes,
      five patients carrying a mutation on the BEST1 gene; 2. previtelliform lesions:
      six eyes, three affected patients; 3. vitelliform lesions: four eyes, two
      affected patients; 4. pseudohypopyon: three eyes, three affected patients; 5.
      vitelliruptive lesions (scrambled egg aspect with dispersion of the vitelliform
      material without sign of atrophy or fibrosis): ten eyes, six affected patients;
      6. atrophic lesions (atrophy with or without residual dispersed material): seven
      eyes, five patients; 7. fibrotic lesions: eight eyes, five patients. Two patients
      presented unilateral Best VMD. Both eyes of two patients presented multifocal
      Best VMD features on fundus examination. Six eyes of four patients have been
      treated for choroidal neovascularization by thermic photocoagulation [one eye],
      photodynamic therapy [three eyes], and intravitreal ranibizumab injection [two
      eyes]. Comparison of interfamilial and intrafamilial clinical data between
      patients did not reveal differences in age, BCVA, and stage of the disease as
      evaluated by fundus autofluorescence, fluorescein angiography, and optical
      coherence tomography (p>0.05). Mean BCVA impairment showed a statistically
      significant correlation to a more advanced stage of the disease (p<0.001).
      CONCLUSIONS: BEST1 mutations were not correlated with the severity of the
      functional and clinical data in the Best VMD patients examined.

PMID- 20057904
TI  - Noninvasive direct detection of ocular mucositis by in vivo confocal microscopy
      in patients treated with S-1.
AB  - PURPOSE: S-1 is an oral antineoplastic agent that contains a prodrug of 5
      fluorouracil and has adverse effects on skin, alimentary tract mucosa, and the
      ocular surface. We investigated the effects of S-1 on the corneal epithelium by
      in vivo confocal microscopy and histopathologic analysis. METHODS: Twelve
      patients with eye problems related to S-1 treatment participated in the study.
      Twenty eyes of ten subjects were evaluated by laser-scanning confocal microscopy.
      Corneal epithelial debridement as a diagnostic therapy and histopathologic
      analysis were performed for five eyes of three subjects affected in the pupillary
      zone of the cornea. RESULTS: Slitlamp examination revealed a local limbal
      abnormality characterized by epithelial invasion toward the center of the cornea
      in all 24 eyes. In vivo confocal microscopy revealed an altered structure of the
      corneal epithelium with abnormal epithelial cells and inflammation. One of five
      specimens subjected to cytologic diagnosis showed moderate dysplasia. Hematoxylin
      and eosin staining showed that each abnormal epithelial sheet lacked the
      stratified structure of the normal corneal epithelium. Immunofluorescence
      analysis revealed the presence of cells positive for one, both, or neither of
      cytokeratins 12 and 4 in each lesion. CONCLUSIONS: S-1 can induce ocular
      mucositis with dysplasia, likely affecting cellular functions, including
      differentiation, of the corneal epithelium. In vivo confocal microscopy allowed
      the noninvasive detection of cellular changes in the cornea as an adverse effect
      of S-1 administration.

PMID- 20057905
TI  - Association of toll-like receptor 2 gene polymorphisms with normal tension
      glaucoma.
AB  - PURPOSE: Toll-like receptor 2 (TLR2) is a transmembrane receptor that mediates
      immune responses to exogenous and endogenous ligands, and interacts with heat
      shock proteins, which are reportedly involved in normal tension glaucoma (NTG).
      We investigated whether TLR2 polymorphisms are associated with NTG. METHODS: 200
      Japanese patients with NTG and 128 healthy Japanese controls were recruited. We
      genotyped five single-nucleotide polymorphisms (SNPs) in the TLR2 gene and
      assessed the allele and haplotype diversities between cases and controls for all
      SNPs. RESULTS: No significant differences in the frequency of TLR2 alleles and
      haplotypes in the NTG cases were detected, compared with the controls.
      CONCLUSIONS: Our study showed no evidence for an association between TLR2
      polymorphisms and NTG. TLR2 polymorphisms may not play an important role in NTG
      pathogenesis in the Japanese population.

PMID- 20057906
TI  - Mutational screening of 10 genes in Chinese patients with microphthalmia and/or
      coloboma.
AB  - PURPOSE: To screen ten genes for mutations in 32 Chinese patients with
      microphthalmia and/or coloboma. METHODS: Genomic DNA was prepared from 32
      unrelated patients with microphthalmia (nine probands) and uveal coloboma (23
      probands). Cycle sequencing was used to detect sequence variations in ten genes,
      including BMP4, VSX2, CRYBA4, GDF6, OTX2, RAX, SIX3, SIX6, SOX2, and LRP6.
      Variations were further evaluated in 96 unrelated controls by using restriction
      fragment length polymorphism (RFLP) or heteroduplex-single strand conformation
      polymorphism (HA-SSCP) analysis. RESULTS: In the ten genes, a novel c.751C>T
      (p.H251Y) in BMP4 was detected in a patient with bilateral microphthalmia and
      unilateral cataract. The c.751C>T variation is also present in his healthy
      brother (and possibly one of the normal parents). In addition, a novel c.608G>A
      (p.R203Q) in SIX6 was identified in an internal control for optimizing
      experimental conditions. The internal control was from a girl with typical
      aniridia and an identified c.718C>T (p.R240X) mutation in PAX6, suggesting the
      c.608G>A variation in SIX6 was unlikely to play a role in her ocular phenotype.
      The c.751C>T in BMP4 and the c.608G>A in SIX6 were not present in the 96 normal
      controls. In addition, 16 nucleotide substitutions, including eight known SNPs
      and eight new synonymous changes, were detected. CONCLUSIONS: Although the
      genetic etiology for microphthalmia and/or coloboma is still elusive, rare
      variations in the related genes, such as c.608 G>A in SIX6 and c.751C>T in BMP4,
      may not be causative. These results further emphasize the importance of careful
      clinical and genetic analysis in making mutation-disease associations.

PMID- 20057907
TI  - N-methyl-N-nitrosourea-induced retinal degeneration in mice is independent of the
      p53 gene.
AB  - PURPOSE: A single systemic administration of N-methyl-N-nitrosourea (MNU) causes
      retinal degeneration involving photoreceptor cell loss within 7 days. MNU-induced
      photoreceptor cell loss is due to apoptosis and is a reliable animal model for
      human retinitis pigmentosa. The purpose of this study was to determine if p53
      contributes to the development of MNU-induced retinal degeneration in mice.
      METHODS: Eight-week-old p53(-/-), p53(+/-), and p53(+/+) mice received an
      intraperitoneal injection of 60 mg/kg bodyweight of MNU. Age-matched p53(+/+)
      mice received the vehicle only (physiologic saline containing 0.05% acetic acid).
      Mice were sacrificed and necropsied 7 days after the treatment. Both eyes were
      examined histologically and morphometrically to determine retinal thickness,
      photoreceptor cell ratio, and retinal damage ratio. RESULTS: No mice died during
      the experiment, but the p53 null mice treated with MNU had a statistically
      significant weight loss compared to the other groups. Histologically, all MNU
      treated mice, regardless of p53 gene status, experienced retinal degeneration
      characterized by photoreceptor cell loss (the disappearance of the outer nuclear
      layer and photoreceptor layer) in both the central and peripheral retina. All MNU
      treated mice had significantly decreased retinal thickness and photoreceptor cell
      ratios at the central and peripheral retina and an increased retinal damage ratio
      compared to the vehicle-treated control. The retinal changes caused by MNU in
      p53(+/+), p53(+/-), and p53(-/-) mice were not significantly different and hence
      were related to a p53-independent apoptotic mechanism. CONCLUSIONS: Because the
      absence of p53 did not prevent photoreceptor cell loss, we conclude that p53 is
      not essential for MNU-mediated photoreceptor cell degeneration.

PMID- 20057908
TI  - Identification of four novel cytochrome P4501B1 mutations (p.I94X, p.H279D,
      p.Q340H, and p.K433K) in primary congenital glaucoma patients.
AB  - PURPOSE: Primary congenital glaucoma (PCG) is an autosomal recessive eye disorder
      that is postulated to result from developmental defects in the anterior eye
      segment. Mutations in the cytochrome P4501B1 (CYP1B1) gene are a predominant
      cause of congenital glaucoma. In this study we identify CYP1B1 mutations in PCG
      patients. METHODS: Twenty-three unrelated PCG patients and 50 healthy controls
      were enrolled in the study. CYP1B1 was screened for mutations by PCR and DNA
      sequencing. RESULTS: DNA sequencing revealed a total of 15 mutations. Out of
      these, four (p.I94X, p.H279D, p.Q340H, and p.K433K) were novel mutations and five
      were known pathogenic mutations. Five coding single nucleotide polymorphisms and
      one intronic single nucleotide polymorphism (rs2617266) were also found.
      Truncating mutations (p.I94X and p.R355X) were associated with the most severe
      disease phenotype. It is possible that patients with two null alleles with no
      catalytic activity may present with a more severe phenotype of the disease
      compared to patients with one null allele (heterozygous). The disease phenotype
      of patients with CYP1B1 mutations was more severe compared with the clinical
      phenotype of patients negative for CYP1B1 mutations. CONCLUSION: Mutations in
      CYP1B1 are a major cause for PCG in our patients. Identifying mutations in
      subjects at risk of developing glaucoma, particularly among relatives of PCG
      patients, is of clinical significance. These developments may help in reducing
      the disease frequency in familial cases. Such studies will be of benefit in the
      identification of pathogenic mutations in different populations and will enable
      us to develop simple and rapid diagnostic tests for analyzing such cases.

PMID- 20057909
TI  - Upregulated IL-21 and IL-21 receptor expression is involved in experimental
      autoimmune uveitis (EAU).
AB  - PURPOSE: Interleukin (IL)-21 has recently been shown to play a vital role in the
      development of many autoimmune diseases. Our study is designed to investigate the
      alteration and possible function of IL-21 in the development of an experimental
      autoimmune uveitis (EAU) model. METHODS: EAU was induced in B10.RIII mice by
      subcutaneous injection of interphotoreceptor retinoid-binding protein (IRBP) 161
      180 emulsified with complete Freund's adjuvant (CFA) and evaluated by clinical
      and histopathologic observation. IL-21 and IL-21R mRNA expressions in cells of
      draining lymph node (DLN) and spleen in EAU and control mice were determined by
      reverse transcription-PCR. The frequencies of interleukin-21 receptor positive
      cells were also examined using flow cytometry. IL-17 levels in the supernatant of
      the cell culture upon IL-21 stimulation were assayed by enzyme-linked
      immunosorbent assay. RESULTS: Results showed that EAU was successfully induced by
      IRBP161-180. Expression of IL-21 mRNA was significantly increased in cells of DLN
      and spleen in EAU compared with recovery phase mice and normal controls. IL-21R
      was also found upregulated in DLN and spleen cells of EAU mice by reverse
      transcription-PCR and flow cytometry. Cells in EAU cultured with IL-21 combined
      with transforming growth factor-beta induced increased production of IL-17.
      CONCLUSION: The findings revealed that increased IL-21 and IL-21R expression may
      be involved in the development of EAU, possibly by promoting IL-17 secretion.

PMID- 20057910
TI  - Hyperoxia-induced lens damage in rabbit: protective effects of N-acetylcysteine.
AB  - PURPOSE: To investigate the efficacies of different concentrations of N
      acetylcysteine (NAC) in preventing hyperoxia-induced lens opacification and
      changes to biochemical parameters in organ-cultured rabbit lenses. METHODS:
      Thirty-six lenses from adult rabbits were divided into the control group (group
      A), the hyperoxia-exposed group (group B), and the hyperoxia-exposed, NAC-treated
      groups: 5 mM NAC (group C), 10 mM NAC (group D), 20 mM NAC (group E), and 40 mM
      NAC (group F). Groups B-F were incubated with hyperoxia (pO(2)>80%) for 4 h per
      day for 7 d. Lens transparency, histology, and enzymatic activities were measured
      after incubation. RESULTS: Gross examination of these lenses revealed some severe
      cortical opacification in group B, and moderate cortical opacification in the
      lenses of groups C and D. There was minimal cortical opacification in groups A,
      E, and F. The activities of Na, K-ATPase, and catalase were significantly
      (p<0.05) lower in group B (38.2%) than in group A (39.9%). It was also lower in
      group E and F lenses (p<0.05), which had higher levels of NAC-protected enzymes.
      The glutathione and water-soluble protein content were significantly lower in
      group B lenses than in group A, E, or F lenses (p<0.05). However, there was no
      difference between group E and F lenses (p>0.05). CONCLUSIONS: The present data
      suggests that NAC (20 mM-40 mM) significantly prevented experimental lenses'
      hyperoxia-induced cortical opacification, indicating NAC's potential role in
      protecting lenses against cataracts induced by high oxygen levels.

PMID- 20057912
TI  - Problem Solving and Computational Skill: Are They Shared or Distinct Aspects of
      Mathematical Cognition?
AB  - The purpose of this study was to explore patterns of difficulty in 2 domains of
      mathematical cognition: computation and problem solving. Third graders (n = 924;
      47.3% male) were representatively sampled from 89 classrooms; assessed on
      computation and problem solving; classified as having difficulty with
      computation, problem solving, both domains, or neither domain; and measured on 9
      cognitive dimensions. Difficulty occurred across domains with the same prevalence
      as difficulty with a single domain; specific difficulty was distributed similarly
      across domains. Multivariate profile analysis on cognitive dimensions and chi
      square tests on demographics showed that specific computational difficulty was
      associated with strength in language and weaknesses in attentive behavior and
      processing speed; problem-solving difficulty was associated with deficient
      language as well as race and poverty. Implications for understanding mathematics
      competence and for the identification and treatment of mathematics difficulties
      are discussed.

PMID- 20057911
TI  - Genetically encoded optical sensors for monitoring of intracellular chloride and
      chloride-selective channel activity.
AB  - This review briefly discusses the main approaches for monitoring chloride (Cl(
      )), the most abundant physiological anion. Noninvasive monitoring of
      intracellular Cl(-) ([Cl(-)]i) is a challenging task owing to two main
      difficulties: (i) the low transmembrane ratio for Cl(-), approximately 10:1; and
      (ii) the small driving force for Cl(-), as the Cl(-) reversal potential (E(Cl))
      is usually close to the resting potential of the cells. Thus, for reliable
      monitoring of intracellular Cl(-), one has to use highly sensitive probes. From
      several methods for intracellular Cl(-) analysis, genetically encoded chloride
      indicators represent the most promising tools. Recent achievements in the
      development of genetically encoded chloride probes are based on the fact that
      yellow fluorescent protein (YFP) exhibits Cl(-)-sensitivity. YFP-based probes
      have been successfully used for quantitative analysis of Cl(-) transport in
      different cells and for high-throughput screening of modulators of Cl(-)
      selective channels. Development of a ratiometric genetically encoded probe,
      Clomeleon, has provided a tool for noninvasive estimation of intracellular Cl(-)
      concentrations. While the sensitivity of this protein to Cl(-) is low (EC(50)
      about 160 mM), it has been successfully used for monitoring intracellular Cl(-)
      in different cell types. Recently a CFP-YFP-based probe with a relatively high
      sensitivity to Cl(-) (EC(50) about 30 mM) has been developed. This construct,
      termed Cl-Sensor, allows ratiometric monitoring using the fluorescence excitation
      ratio. Of particular interest are genetically encoded probes for monitoring of
      ion channel distribution and activity. A new molecular probe has been constructed
      by introducing into the cytoplasmic domain of the Cl(-)-selective glycine
      receptor (GlyR) channel the CFP-YFP-based Cl-Sensor. This construct, termed
      BioSensor-GlyR, has been successfully expressed in cell lines. The new
      genetically encoded chloride probes offer means of screening pharmacological
      agents, analysis of Cl(-) homeostasis and functions of Cl(-)-selective channels
      under different physiological and pathological conditions.

PMID- 20057913
TI  - Approaching the Transition to Adulthood: Distinctive Profiles of Adolescents
      Aging out of the Child Welfare System.
AB  - The transition to adulthood is marked by new roles and responsibilities in such
      interrelated domains as education, employment, and family formation. This study
      investigates the capacity of adolescents on the verge of emancipation from the
      child welfare system to navigate this transition. To explore heterogeneity in
      adolescents' preparation for independent living, person-oriented methods are
      applied to a large, representative sample of youth about to exit foster care. The
      analysis suggests four subpopulations defined by distinctive profiles on
      indicators reflecting multiple domains of life experience. Identifying the
      particular needs and challenges of subpopulations has implications for efforts to
      match adolescents aging out of the child welfare system with appropriate
      services.

PMID- 20057914
TI  - Identification of cancer-associated gene clusters and genes via clustering
      penalization.
AB  - Identification of genes associated with cancer development and progression using
      microarray data is challenging because of the high dimensionality and cluster
      structure of gene expressions. Here the clusters are composed of multiple genes
      with coordinated biological functions and/or correlated expressions. In this
      article, we first propose a hybrid approach for clustering gene expressions. The
      hybrid approach uses both pathological pathway information and correlations of
      gene expressions. We propose using the group bridge, a novel clustering
      penalization approach, for analysis of cancer microarray data. The group bridge
      approach explicitly accounts for the cluster structure of gene expressions, and
      is capable of selecting gene clusters and genes within those selected clusters
      that are associated with cancer. We also develop an iterative algorithm for
      computing the group bridge estimator. Analysis of three cancer microarray
      datasets shows that the proposed approach can identify biologically meaningful
      gene clusters and genes within those identified clusters.

PMID- 20057915
TI  - Diffusion of Philadelphia's No-Smoking Policy to Chinese Businesses.
AB  - The study assessed the extent that Philadelphia's smoking ordinance diffused to
      Chinatown businesses and identified attitudinal and other barriers to
      implementation. Guided by constructs from Diffusion of Innovations and Theory of
      Planned Behavior, a cross-sectional study was conducted. The majority of business
      owners and employees lacked in-depth knowledge of relevant details of the policy,
      suggesting that the extent of its diffusion was limited. Retail businesses were
      more likely to witness smoking post-enactment than restaurants and had more
      difficulty with implementation. A multi-faceted diffusion strategy through
      communication channels familiar to the Chinatown community is needed to improve
      implementation and compliance.

PMID- 20057916
TI  - Music, Lyrics, and Dangerous Things.

PMID- 20057917
TI  - Conclusions and Directions for Future Research Concerning Racial Socialization.

PMID- 20057918
TI  - Cohesion and conflict: family influences on adolescent alcohol use in immigrant
      Latino families.
AB  - This study examines how cohesion and parent-child conflict relate to alcohol use
      among Mexican-heritage adolescents. The sample consists of 120 adolescents (14 to
      18 years) participants from the Southwest sub-sample of the Latino Acculturation
      and Health Project. Lifetime and recent alcohol use and binge drinking were
      tested. Results from the logistic regressions identified high and low levels of
      family cohesion as a risk factor for alcohol use compared to medium levels of
      cohesion, and parent-child conflict predicted lifetime use and binge drinking.
      Low and high family cohesion levels appear to be especially problematic among
      Mexican adolescents who are trying to navigate two different cultural worlds.
      Although high family cohesion is often a characteristic of Mexican families,
      Mexican-heritage adolescents may view high family cohesion as a hindrance to
      their own independence. Unresolved conflict seems to be connected to children's
      problem behaviors and alcohol misuse could be utilized by adolescents as a
      mechanism to reduce emotional distress caused by family tensions.

PMID- 20057919
TI  - Statistical Power Calculations for Clustered Continuous Data.
AB  - To calculate the sample size for a research study it is important to take into
      account several aspects of the study design. In particular, one needs to take
      into account the hypotheses being tested, the study design, the sampling design,
      and the method to be used for the analysis. In this paper we propose a simple
      method to calculate sample size for clustered continuous data under various
      scenarios of study design.

PMID- 20057920
TI  - Does the Presence of a Smoking Cessation Clinical Trial Affect Staff Practices
      Related to Smoking?
AB  - This study investigated whether organizational changes occurred when nicotine
      treatments were tested in specialty care clinics. Two intervention clinics (one
      drug treatment and one HIV-care) participated in clinical trials for nicotine
      treatment. Three clinics (two drug and one HIV-care) were control clinics. Staff
      in the intervention clinics (n=57) and in the control clinics (n=62) were
      surveyed at baseline and 18 months later. Staff surveys concerned nicotine
      related knowledge, beliefs about treating smoking, self-efficacy in delivering
      such treatment, nicotine related practices, and barriers to providing nicotine
      treatment. Mean scale scores at 18 months were no different in clinics
      participating in the clinical trials from the control group for any of the five
      scales (knowledge, practices, barriers, efficacy, and beliefs). The presence of a
      smoking cessation clinical trial did not influence staff knowledge, attitudes, or
      practices related to smoking in these clinics. More specific organizational
      intervention may influence staff practices related to addressing smoking among
      clients in drug treatment and HIV-care clinics.

PMID- 20057921
TI  - Application of Proteomic Analysis to Renal Disease in the Clinic.

PMID- 20057922
TI  - The Combination of Ecological and Case-Control Data.
AB  - Ecological studies, in which data are available at the level of the group, rather
      than at the level of the individual, are susceptible to a range of biases due to
      their inability to characterize within-group variability in exposures and
      confounders. In order to overcome these biases, we propose a hybrid design in
      which ecological data are supplemented with a sample of individual-level case
      control data. We develop the likelihood for this design and illustrate its
      benefits via simulation, both in bias reduction when compared to an ecological
      study, and in efficiency gains relative to a conventional case-control study. An
      interesting special case of the proposed design is the situation where ecological
      data are supplemented with case-only data. The design is illustrated using a
      dataset of county-specific lung cancer mortality rates in the state of Ohio from
      1988.

PMID- 20057923
TI  - THE MOTHERS AND TODDLERS PROGRAM: Preliminary Findings From an Attachment-Based
      Parenting Intervention for Substance-Abusing Mothers.
AB  - The authors examined pilot data from an attachment-based parenting intervention
      for substance-abusing mothers of toddlers (ages 12-36 months). The Mothers and
      Toddlers Program (MTP) is a 20-week individual therapy intervention that aims to
      help mothers develop more balanced representations of their children and improve
      their capacity for reflective functioning (i.e., recognition of the intentional
      nature of children's behavior). The authors hypothesized that improvement in
      maternal representational balance and maternal capacity for reflective
      functioning would correspond with improvements in maternal behavior with toddlers
      (e.g., sensitivity to cues, responsiveness to distress, and social-emotional
      growth fostering) and reduction in maternal psychiatric distress and substance
      abuse. Eight mothers who completed MTP showed moderate improvements in
      representational balance and reflective functioning, and these changes
      corresponded with significant improvements in maternal behaviors with toddlers.
      The authors also compared MTP completers and noncompleters on sociodemographic
      and psychosocial indexes and examined the validity of the intervention's proposed
      mechanisms of change. Preliminary findings support the importance of attachment
      mechanisms and indicate that attachment-based interventions may strengthen
      substance-abusing mothers' capacities to foster their toddlers' socioemotional
      development.

PMID- 20057924
TI  - The Relationship between Parental Efficacy and Depressive Symptoms in a Diverse
      Sample of Low Income Mothers.
AB  - We examined the relationship between parental efficacy and depressive symptoms in
      a diverse sample of low income mothers. The sample consisted of 607 European
      American, African American, and Hispanic mothers who participated in The Early
      Steps Project, a multi-site, longitudinal, preventative intervention study.
      Parental efficacy was found to be significantly associated with depressive
      symptoms in the entire sample of low income mothers. Ethnicity moderated results,
      however, such that parental efficacy was significantly associated with depressive
      symptoms for European American mothers but was not for the African American and
      Hispanic mothers. Ethnic differences in the various categories of depressive
      symptoms (i.e., total, somatic, and psychological) were also explored, with the
      results showing that African American mothers reported higher levels of
      depressive symptoms than both European American and Hispanic mothers in each of
      the categories. The theoretical and clinical implications of these results are
      discussed.

PMID- 20057925
TI  - Nonparametric Signal Extraction and Measurement Error in the Analysis of
      Electroencephalographic Activity During Sleep.
AB  - We introduce methods for signal and associated variability estimation based on
      hierarchical nonparametric smoothing with application to the Sleep Heart Health
      Study (SHHS). SHHS is the largest electroencephalographic (EEG) collection of
      sleep-related data, which contains, at each visit, two quasi-continuous EEG
      signals for each subject. The signal features extracted from EEG data are then
      used in second level analyses to investigate the relation between health,
      behavioral, or biometric outcomes and sleep. Using subject specific signals
      estimated with known variability in a second level regression becomes a
      nonstandard measurement error problem. We propose and implement methods that take
      into account cross-sectional and longitudinal measurement error. The research
      presented here forms the basis for EEG signal processing for the SHHS.

PMID- 20057926
TI  - Development and validation of a sensitive entropy-based measure for the water
      maze.
AB  - In the water maze, mice are trained to navigate to an escape platform located
      below the water's surface, and spatial learning is most commonly evaluated in a
      probe test in which the platform is removed from the pool. While contemporary
      tracking software provides precise positional information of mice for the
      duration of the probe test, existing performance measures (e.g., percent quadrant
      time, platform crossings) fail to exploit fully the richness of this positional
      data. Using the concept of entropy (H), here we develop a new measure that
      considers both how focused the search is and the degree to which searching is
      centered on the former platform location. To evaluate how H performs compared to
      existing measures of water maze performance we compiled five separate databases,
      containing more than 1600 mouse probe tests. Random selection of individual
      trials from respective databases then allowed us to simulate experiments with
      varying sample and effect sizes. Using this Monte Carlo-based method, we found
      that H outperformed existing measures in its ability to detect group differences
      over a range of sample or effect sizes. Additionally, we validated the new
      measure using three models of experimentally induced hippocampal dysfunction: (1)
      complete hippocampal lesions, (2) genetic deletion of alphaCaMKII, a gene
      implicated in hippocampal behavioral and synaptic plasticity, and (3) a mouse
      model of Alzheimer's disease. Together, these data indicate that H offers greater
      sensitivity than existing measures, most likely because it exploits the richness
      of the precise positional information of the mouse throughout the probe test.

PMID- 20057927
TI  - Towards the sensory nature of the carotid body: hering, de castro and
      heymansdagger.
AB  - The carotid body or glomus caroticum is a chemosensory organ bilaterally located
      between the external and internal carotid arteries. Although known by anatomists
      since the report included by Von Haller and Taube in the mid XVIII century, its
      detailed study started the first quarter of the XX. The Austro-German
      physiologist Heinrich E. Hering studied the cardio-respiratory reflexes searched
      for the anatomical basis of this reflex in the carotid sinus, while the Ghent
      School leaded by the physio-pharmacologists Jean-Francois Heymans and his son
      Corneille focussed in the cardio-aortic reflexogenic region. In 1925, Fernando De
      Castro, one of the youngest and more brilliant disciples of Santiago Ramon y
      Cajal at the Laboratorio de Investigaciones Biologicas (Madrid, Spain), profited
      from some original novelties in histological procedures to study the fine
      structure and innervation of the carotid body. De Castro unravelled them in a
      series of scientific papers published between 1926 and 1929, which became the
      basis to consider the carotid body as a sensory receptor (or chemoreceptor) to
      detect the chemical changes in the composition of the blood. Indeed, this was the
      first description of arterial chemoreceptors. Impressed by the novelty and
      implications of the work of De Castro, Corneille Heymans invited the Spanish
      neurologist to visit Ghent on two occasions (1929 and 1932), where both performed
      experiences together. Shortly after, Heymans visited De Castro at the Instituto
      Cajal (Madrid). From 1932 to 1933, Corneille Heymans focused all his attention on
      the carotid body his physiological demonstration of De Castro's hypothesis
      regarding chemoreceptors was awarded with the Nobel Prize in Physiology or
      Medicine in 1938, just when Spain was immersed in its catastrophic Civil War.

PMID- 20057928
TI  - Inhibition of NMDARs in the Nucleus Reticularis of the Thalamus Produces Delta
      Frequency Bursting.
AB  - Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG
      oscillations in the thalamocortical system. It is surprising that an antagonist
      of an excitatory neurotransmitter should trigger such activity, and the mechanism
      is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic
      cells, thus producing disinhibition. To test this hypothesis, we investigated the
      effect of NMDAR antagonist (APV) on cells of the nucleus reticularis (nRT) in rat
      brain slices, a thalamic nucleus that can serve as a pacemaker for
      thalamocortical delta oscillations and that is composed entirely of GABAergic
      neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This
      occurs because these cells have an unusual form of NMDAR (probably NR2C) that
      contributes inward current at resting potential in response to ambient glutamate.
      The hyperpolarization produced by APV is sufficient to deinactivate T-type
      calcium channels, and these trigger rhythmic bursting at delta frequency. The APV
      induced delta frequency bursting is abolished by dopamine D2 receptor antagonist,
      indicating that dopamine and NMDAR antagonist work synergistically to stimulate
      delta frequency bursting. Our results have significant implications concerning
      the electrophysiological basis of schizophrenia and bring together the NMDAR
      hypofunction, dopamine, and GABA theories of the disease. Our results suggest
      that NMDAR hypofunction and dopamine work synergistically on the GABAergic cells
      of the nRT to generate the delta frequency EEG oscillations, a thalamocortical
      dysrhythmia (TCD) in the awake state that is an established abnormality in
      schizophrenia.

PMID- 20057929
TI  - A new photosensory function for simple photoreceptors, the intrinsically
      photoresponsive neurons of the sea slug onchidium.
AB  - Simple photoreceptors, namely intrinsically light-sensitive neurons without
      microvilli and/or cilia, have long been known to exist in the central ganglia of
      crayfish, Aplysia, Onchidium, and Helix. These simple photoreceptors are not only
      first-order photosensory cells, but also second-order neurons (interneurons),
      relaying several kinds of sensory synaptic inputs. Another important issue is
      that the photoresponses of these simple photoreceptors show very slow kinetics
      and little adaptation. These characteristics suggest that the simple
      photoreceptors of the Onchidium have a function in non-image-forming vision,
      different from classical eye photoreceptors used for cording dynamic images of
      vision. The cited literature provides evidence that the depolarizing and
      hyperpolarizing photoresponses of simple photoreceptors play a role in the long
      lasting potentiation of synaptic transmission of excitatory and inhibitory
      sensory inputs, and as well as in the potentiation and the suppression of the
      subsequent behavioral outputs. In short, we suggest that simple photoreceptors
      operate in the general potentiation of synaptic transmission and subsequent motor
      output; i.e., they perform a new photosensory function.

PMID- 20057931
TI  - Eu oxidation state in fluorozirconate-based glass ceramics.
AB  - The influence of InF(3) doping and remelting on Eu-doped fluorozirconate-based
      glass ceramics was investigated using near-edge x-ray absorption and optical
      spectroscopy. It was found that the addition of InF(3) to the melt decreases the
      Eu(2+)Eu(3+) mole ratio, while remelting leads to a significant change in the
      Eu(2+)Eu(3+) ratio in favor of Eu(2+). Photoluminescence spectroscopy shows that
      additional annealing steps lead to the formation of BaCl(2) nanoparticles in the
      glass. In as-made glass ceramics containing InF(3), a phase transition of the
      nanoparticles from hexagonal to orthorhombic structure is observed. This phase
      transition is not observed in the remelted glasses studied here.

PMID- 20057930
TI  - Assessing the construct validity of aberrant salience.
AB  - We sought to validate the psychometric properties of a recently developed
      paradigm that aims to measure salience attribution processes proposed to
      contribute to positive psychotic symptoms, the Salience Attribution Test (SAT).
      The "aberrant salience" measure from the SAT showed good face validity in
      previous results, with elevated scores both in high-schizotypy individuals, and
      in patients with schizophrenia suffering from delusions. Exploring the construct
      validity of salience attribution variables derived from the SAT is important,
      since other factors, including latent inhibition/learned irrelevance (LIrr),
      attention, probabilistic reward learning, sensitivity to probability, general
      cognitive ability and working memory could influence these measures. Fifty
      healthy participants completed schizotypy scales, the SAT, a LIrr task, and a
      number of other cognitive tasks tapping into potentially confounding processes.
      Behavioural measures of interest from each task were entered into a principal
      components analysis, which yielded a five-factor structure accounting for
      approximately 75% of the variance in behaviour. Implicit aberrant salience was
      found to load onto its own factor, which was associated with elevated
      "Introvertive Anhedonia" schizotypy, replicating our previous finding. LIrr
      loaded onto a separate factor, which also included implicit adaptive salience,
      but was not associated with schizotypy. Explicit adaptive and aberrant salience,
      along with a measure of probabilistic learning, loaded onto a further factor,
      though this also did not correlate with schizotypy. These results suggest that
      the measures of LIrr and implicit adaptive salience might be based on similar
      underlying processes, which are dissociable both from implicit aberrant salience
      and explicit measures of salience.

PMID- 20057932
TI  - Elastomeric microfluidic diode and rectifier work with Newtonian fluids.
AB  - We report on two microfluidic elastomeric autoregulatory devices-a diode and a
      rectifier. They exhibit physically interesting and complex nonlinear behaviors
      (saturation, bias-dependent resistance, and rectification) with a Newtonian
      fluid. Due to their autoregulatory properties, they operate without active
      external control. As a result, they enable increased microfluidic device density
      and overall system miniaturization. The demonstrated diode and rectifier would
      also be useful components in future microfluidic logic circuitry.

PMID- 20057933
TI  - Determining k channel activation curves from k channel currents often requires
      the goldman-hodgkin-katz equation.
AB  - Potassium ion current in nerve membrane, I(K), has traditionally been described
      by I(K) = g(K)(V - E(K)), where g(K) is the K ion conductance, V is membrane
      potential and E(K) is the K(+) Nernst potential. This description has been
      unchallenged by most investigators in neuroscience since its introduction almost
      60 years ago. The problem with the I(K) approximately (V - E(K)) proportionality
      is that it is inconsistent with the unequal distribution of K ions in the intra-
      and extracellular bathing media. Under physiological conditions the intracellular
      K(+) concentration is significantly higher than the extracellular concentration.
      Consequently, the slope conductance at potentials positive to E(K) cannot be the
      same as that for potentials negative to E(K), as the linear proportionality
      between I(K) and (V - E(K)) requires. Instead I(K) has a non-linear dependence on
      (V - E(K)) which is well described by the Goldman-Hodgkin-Katz equation. The
      implications of this result for K(+) channel gating and membrane excitability are
      reviewed in this report.

PMID- 20057934
TI  - A defined network of fast-spiking interneurons in orbitofrontal cortex: responses
      to behavioral contingencies and ketamine administration.
AB  - Orbitofrontal cortex (OFC) is a region of prefrontal cortex implicated in the
      motivational control of behavior and in related abnormalities seen in psychosis
      and depression. It has been hypothesized that a critical mechanism in these
      disorders is the dysfunction of GABAergic interneurons that normally regulate
      prefrontal information processing. Here, we studied a subclass of interneurons
      isolated in rat OFC using extracellular waveform and spike train analysis. During
      performance of a goal-directed behavioral task, the firing of this class of
      putative fast-spiking (FS) interneurons showed robust temporal correlations
      indicative of a functionally coherent network. FS cell activity also co-varied
      with behavioral response latency, a key indicator of motivational state. Systemic
      administration of ketamine, a drug that can mimic psychosis, preferentially
      inhibited this cell class. Together, these results support the idea that OFC-FS
      interneurons form a critical link in the regulation of motivation by prefrontal
      circuits during normal and abnormal brain and behavioral states.

PMID- 20057935
TI  - What are the Effects of Severe Visual Impairment on the Cortical Organization and
      Connectivity of Primary Visual Cortex?
AB  - The organization and connections of the primary visual area (V1) were examined in
      mice that lacked functional rods (Gnat-/-), but had normal cone function. Because
      mice are nocturnal and rely almost exclusively on rod vision for normal
      behaviors, the Gnat-/- mice used in the present study are considered functionally
      blind. Our goal was to determine if visual cortex is reorganized in these mice,
      and to examine the neuroanatomical connections that may subserve reorganization.
      We found that most neurons in V1 responded to auditory, or some combination of
      auditory, somatosensory, and/or visual stimulation. We also determined that
      cortical connections of V1 in Gnat-/- mice were similar to those in normal
      animals, but even in normal animals, there is sparse input from auditory cortex
      (AC) to V1. An important observation was that most of the subcortical inputs to
      V1 were from thalamic nuclei that normally project to V1 such as the lateral
      geniculate (LG), lateral posterior (LP), and lateral dorsal (LD) nuclei. However,
      V1 also received some abnormal subcortical inputs from the anterior thalamic
      nuclei, the ventral posterior, the ventral lateral and the posterior nuclei.
      While the vision generated from the small number of cones appears to be
      sufficient to maintain most of the patterns of normal connectivity, the sparse
      abnormal thalamic inputs to VI, existing inputs from AC, and possibly abnormal
      inputs to LG and LP may be responsible for generating the alterations in the
      functional organization of V1.

PMID- 20057936
TI  - Genetic control of active neural circuits.
AB  - The use of molecular tools to study the neurobiology of complex behaviors has
      been hampered by an inability to target the desired changes to relevant groups of
      neurons. Specific memories and specific sensory representations are sparsely
      encoded by a small fraction of neurons embedded in a sea of morphologically and
      functionally similar cells. In this review we discuss genetics techniques that
      are being developed to address this difficulty. In several studies the use of
      promoter elements that are responsive to neural activity have been used to drive
      long-lasting genetic alterations into neural ensembles that are activated by
      natural environmental stimuli. This approach has been used to examine neural
      activity patterns during learning and retrieval of a memory, to examine the
      regulation of receptor trafficking following learning and to functionally
      manipulate a specific memory trace. We suggest that these techniques will provide
      a general approach to experimentally investigate the link between patterns of
      environmentally activated neural firing and cognitive processes such as
      perception and memory.

PMID- 20057938
TI  - Surface profile-controlled close-packed Si nanorod arrays for self-cleaning
      antireflection coatings.
AB  - We demonstrate the fabrication of surface profile-controlled close-packed Si
      nanorod arrays (NRAs), using a scalable and integrated circuit compatible process
      combining colloidal lithography and reactive ion etching. Si NRAs exhibit
      broadband, omnidirectional, and polarization-insensitive antireflection (AR)
      properties and enhance the hydrophobicity. The effect of surface profiles of
      periodic NRAs on the AR and hydrophobicity was investigated systematically. The
      Si NRAs function as both self-cleaning and AR layers, which offer a promising
      approach to enhance the solar cell energy conversion efficiency.

PMID- 20057939
TI  - Economic aspects of chronic diseases in Vietnam.
AB  - INTRODUCTION: There remains a lack of information on economic aspects of chronic
      diseases. This paper, by gathering available and relevant research findings, aims
      to report and discuss current evidence on economic aspects of chronic diseases in
      Vietnam. METHODS: DATA USED IN THIS PAPER WERE OBTAINED FROM VARIOUS INFORMATION
      SOURCES: international and national journal articles and studies, government
      documents and publications, web-based statistics and fact sheets. RESULTS: In
      Vietnam, chronic diseases were shown to be leading causes of deaths, accounting
      for 66% of all deaths in 2002. The burdens caused by chronic disease morbidity
      and risk factors are also substantial. Poorer people in Vietnam are more
      vulnerable to chronic diseases and their risk factors, other than being
      overweight. The estimated economic loss caused by chronic diseases for Vietnam in
      2005 was about US$20 million (0.033% of annual national GDP). Chronic diseases
      were also shown to cause economic losses for families and individuals in Vietnam.
      Both population-wide and high-risk individual interventions against chronic
      disease were shown to be cost-effective in Vietnam. CONCLUSION: Given the
      evidence from this study, actions to prevent chronic diseases in Vietnam are
      clearly urgent. Further research findings are required to give greater insights
      into economic aspects of chronic diseases in Vietnam.

PMID- 20057937
TI  - Vulnerability to stroke: implications of perinatal programming of the
      hypothalamic-pituitary-adrenal axis.
AB  - Chronic stress is capable of exacerbating each major, modifiable, endogenous risk
      factor for cerebrovascular and cardiovascular disease. Indeed, exposure to stress
      can increase both the incidence and severity of stroke, presumably through
      activation of the hypothalamic-pituitary-adrenal (HPA) axis. Now that
      characterization of the mechanisms underlying epigenetic programming of the HPA
      axis is well underway, there has been renewed interest in examining the role of
      early environment on the evolution of health conditions across the entire
      lifespan. Indeed, neonatal manipulations in rodents that reduce stress
      responsivity, and subsequent life-time exposure to glucocorticoids, are
      associated with a reduction in the development of neuroendocrine,
      neuroanatomical, and cognitive dysfunctions that typically progress with age.
      Although improved day to day regulation of the HPA axis also may be accompanied
      by a decrease in stroke risk, evidence from rodent studies suggest that an
      associated cost could be increased susceptibility to inflammation and neuronal
      death in the event that a stroke does occur and the individual is exposed to
      persistently elevated corticosteroids. Given its importance in regulation of
      health and disease states, any long-term modulation of the HPA axis is likely to
      be associated with both benefits and potential risks. The goals of this review
      article are to examine (1) the clinical and experimental data suggesting that
      neonatal experiences can shape HPA axis regulation, (2) the influence of stress
      and the HPA axis on stroke incidence and severity, and (3) the potential for
      neonatal programming of the HPA axis to impact adult cerebrovascular health.

PMID- 20057940
TI  - Regulation of enzyme activity through interactions with nanoparticles.
AB  - The structure and function of an enzyme can be altered by nanoparticles (NPs).
      The interaction between enzyme and NPs is governed by the key properties of NPs,
      such as structure, size, surface chemistry, charge and surface shape. Recent
      representative studies on the NP-enzyme interactions and the regulation of enzyme
      activity by NPs with different size, composition and surface modification are
      reviewed.

PMID- 20057941
TI  - Effects of acrylamide on the activity and structure of human brain creatine
      kinase.
AB  - Acrylamide is widely used worldwide in industry and it can also be produced by
      the cooking and processing of foods. It is harmful to human beings, and human
      brain CK (HBCK) has been proposed to be one of the important targets of
      acrylamide. In this research, we studied the effects of acrylamide on HBCK
      activity, structure and the potential binding sites. Compared to CKs from rabbit,
      HBCK was fully inactivated at several-fold lower concentrations of acrylamide,
      and exhibited distinct properties upon acrylamide-induced inactivation and
      structural changes. The binding sites of acrylamide were located at the cleft
      between the N- and C-terminal domains of CK, and Glu232 was one of the key
      binding residues. The effects of acrylamide on CK were proposed to be isoenzyme-
      and species-specific, and the underlying molecular mechanisms were discussed.

PMID- 20057942
TI  - Recent advances in synthetic bioelastomers.
AB  - This article reviews the degradability of chemically synthesized bioelastomers,
      mainly designed for soft tissue repair. These bioelastomers involve biodegradable
      polyurethanes, polyphosphazenes, linear and crosslinked poly(ether/ester)s,
      poly(epsilon-caprolactone) copolymers, poly(1,3-trimethylene carbonate) and their
      copolymers, poly(polyol sebacate)s, poly(diol-citrates) and poly(ester amide)s.
      The in vitro and in vivo degradation mechanisms and impact factors influencing
      degradation behaviors are discussed. In addition, the molecular designs,
      synthesis methods, structure properties, mechanical properties, biocompatibility
      and potential applications of these bioelastomers were also presented.

PMID- 20057943
TI  - Evaluation of depigmenting activity by 8-hydroxydaidzein in mouse B16 melanoma
      cells and human volunteers.
AB  - In our previous study, 8-hydroxydaidzein (8-OHDe) was demonstrated to be a potent
      and unique suicide substrate of mushroom tyrosinase. In this study, the compound
      was evaluated for in vitro cellular tyrosinase and melanogenesis inhibitory
      activities in mouse B16 melanoma cells and for in vivo skin-whitening activity in
      human volunteers. Tyrosinase activity and melanogenesis in the cell culture
      incubated with 10 microM of 8-OHDe were decreased to 20.1% and 51.8% of control,
      respectively, while no obvious cytotoxicity was observed in this concentration.
      In contrast, a standard tyrosinase inhibitor, kojic acid, showed 69.9% and 71.3%
      of control in cellular tyrosinase and melanogenesis activity, respectively, at a
      concentration as high as 100 microM. Hence, 8-OHDe exhibited more than an
      inhibitory effects on melanin production in B16 cells 10-fold stronger than kojic
      acid. In addition, when a cream containing 4% 8-OHDe was applied to human skin in
      an in vivo study, significant increases in the dL*-values were observed after
      three weeks. Moreover, the increase in the dL*-values after 8-week treatment with
      4% 8-OHDe (from -0.57 to 1.94) is stronger than those of 2% 8-OHDe treatment
      (from 0.26 to 0.94) and 2% ascorbic acid-2-glucoside treatment (from 0.07 to
      1.54). From the results of the study, it was concluded that 8-OHDe, the potent
      suicide substrate of mushroom tyrosinase, has depigmenting activities in both
      mouse melanoma cells and in human volunteers. Thus, the compound has significant
      potential for use in cosmetics as a skin-whitening ingredient.

PMID- 20057944
TI  - Biodegradation of poly(butylene succinate) powder in a controlled compost at 58
      degrees C evaluated by naturally-occurring carbon 14 amounts in evolved CO(2)
      based on the ISO 14855-2 method.
AB  - The biodegradabilities of poly(butylene succinate) (PBS) powders in a controlled
      compost at 58 degrees C have been studied using a Microbial Oxidative Degradation
      Analyzer (MODA) based on the ISO 14855-2 method, entitled "Determination of the
      ultimate aerobic biodegradability of plastic materials under controlled
      composting conditions-Method by analysis of evolved carbon dioxide-Part 2:
      Gravimetric measurement of carbon dioxide evolved in a laboratory-scale test".
      The evolved CO(2) was trapped by an additional aqueous Ba(OH)(2) solution. The
      trapped BaCO(3) was transformed into graphite via a serial vaporization and
      reduction reaction using a gas-tight tube and vacuum manifold system. This
      graphite was analyzed by accelerated mass spectrometry (AMS) to determine the
      percent modern carbon [pMC (sample)] based on the (14)C radiocarbon
      concentration. By using the theory that pMC (sample) was the sum of the pMC
      (compost) (109.87%) and pMC (PBS) (0%) as the respective ratio in the determined
      period, the CO(2) (respiration) was calculated from only one reaction vessel. It
      was found that the biodegradabilities determined by the CO(2) amount from PBS in
      the sample vessel were about 30% lower than those based on the ISO method. These
      differences between the ISO and AMS methods are caused by the fact that part of
      the carbons from PBS are changed into metabolites by the microorganisms in the
      compost, and not changed into CO(2).

PMID- 20057945
TI  - Theoretical study on reactions of triplet excited state thioxanthone with indole.
AB  - In the present work, a theoretical study on the deactivation of triplet excited
      (T(1)) state thioxanthone (TX) by indole (INH) was performed, based on density
      functional theory calculations. Three feasible pathways, namely direct electron
      transfer from INH to T(1) state TX, electron transfer followed by proton transfer
      from INH(.+) to TX(.-), and H-atom transfer from nitrogen of INH to keto oxygen
      of T(1) state TX, were proposed theoretically to be involved in T(1) state TX
      deactivation by INH.

PMID- 20057947
TI  - Modelling catalyst surfaces using DFT cluster calculations.
AB  - We review our recent theoretical DFT cluster studies of a variety of industrially
      relevant catalysts such as TiO(2), gamma-Al(2)O(3), V(2)O(5)-WO(3)-TiO(2) and
      Ni/Al(2)O(3). Aspects of the metal oxide surface structure and the stability and
      structure of metal clusters on the support are discussed as well as the
      reactivity of surfaces, including their behaviour upon poisoning. It is
      exemplarily demonstrated how such theoretical considerations can be combined with
      DRIFT and XPS results from experimental studies.

PMID- 20057946
TI  - Polyphenols from cocoa and vascular health-a critical review.
AB  - Cocoa is a rich source of dietary polyphenols. In vitro as well as cell culture
      data indicate that cocoa polyphenols may exhibit antioxidant and anti
      inflammatory, as well as anti-atherogenic activity. Several molecular targets
      (e.g., nuclear factor kappa B, endothelial nitric oxide synthase, angiotensin
      converting enzyme) have been recently identified which may partly explain
      potential beneficial cardiovascular effects of cocoa polyphenols. However cocoa
      polyphenol concentrations, as used in many cell culture studies, are not
      physiologically achievable. Bioavailability studies indicate that plasma
      concentrations of cocoa polyphenols following dietary intake are low and in the
      nanomolar range. Human studies regarding the effect of cocoa polyphenols on
      vascular health are often underpowered and lack a rigorous study design. If
      dietary cocoa polyphenol intake is due to chocolate its high energy content needs
      to be taken into account. In order to determine potential health benefits of
      cocoa polyphenols large scale, long term, randomized, placebo controlled studies,
      (ideally with a cross-over design) as well as prospective studies are warranted.

PMID- 20057948
TI  - Extraction of Teucrium manghuaense and evaluation of the bioactivity of its
      extract.
AB  - The ethanol extract of Teucrium manghuaense grown in Hainan province (China) was
      analysed by GC and GC/MS. Of the constituents 84-96% were identified on the basis
      of their GC retention times and their mass spectra in regard to authentic
      compounds. The results revealed that it contained 9-methyl-9
      azabicyclo[4.2.1]nonane (7.43%), 2-methylpyrrolidine (19.42%), 3,7,11,15
      tetramethyl-2-hexadecen-1-ol (10.84%), and squalene (28.55%), as major
      components, constituting 66.24% of the extract. The chemical characterization of
      the ethanol extract by GC/MS also allowed identification of 1-octen-3-one
      (3.41%), 2-pentyl-piperidine (2.25%), 1-(2-methyl-1-propenyl)-piperidine (4.63%),
      2,2'-diethoxy-5,5'-bi-1-pyrroline (0.41%), (Z,Z,Z)-9,12,15-octadecatrieniic acid,
      2,3-dihydroxypropyl ester (1.56%), vitamin E (2.95%) and stigmasterol (1.39%).
      Finally, the antioxidant and anti-tumor activities of the ethanol extract have
      been evaluated. Results show that the extract of Teucrium manghuaense leaf
      possesses strong DPPH(-), hydroxyl radical scavenging activity and anti-tumor
      activity.

PMID- 20057949
TI  - First-principles molecular dynamics calculations of the equation of state for
      tantalum.
AB  - The equation of state of tantalum (Ta) has been investigated to 100 GPa and 3,000
      K using the first-principles molecular dynamics method. A large volume dependence
      of the thermal pressure of Ta was revealed from the analysis of our data. A
      significant temperature dependence of the calculated effective Gruneisen
      parameters was confirmed at high pressures. This indicates that the conventional
      approach to analyze thermal properties using the Mie-Gruneisen approximation is
      likely to have a significant uncertainty in determining the equation of state for
      Ta, and that an intrinsic anharmonicity should be considered to analyze the
      equation of state.

PMID- 20057950
TI  - Improved adhesion, growth and maturation of vascular smooth muscle cells on
      polyethylene grafted with bioactive molecules and carbon particles.
AB  - High-density polyethylene (PE) foils were modified by an Ar(+) plasma discharge
      and subsequent grafting with biomolecules, namely glycine (Gly), polyethylene
      glycol (PEG), bovine serum albumin (BSA), colloidal carbon particles (C) or BSA
      and C (BSA + C). As revealed by atomic force microscopy (AFM), goniometry and
      Rutherford Backscattering Spectroscopy (RBS), the surface chemical structure and
      surface morphology of PE changed dramatically after plasma treatment. The contact
      angle decreased for the samples treated by plasma, mainly in relation to the
      formation of oxygen structures during plasma irradiation. A further decrease in
      the contact angle was obvious after glycine and PEG grafting. The increase in
      oxygen concentration after glycine and PEG grafting proved that the two molecules
      were chemically linked to the plasma-activated surface. Plasma treatment led to
      ablation of the PE surface layer, thus the surface morphology was changed and the
      surface roughness was increased. The materials were then seeded with vascular
      smooth muscle cells (VSMC) derived from rat aorta and incubated in a DMEM medium
      with fetal bovine serum. Generally, the cells adhered and grew better on modified
      rather than on unmodified PE samples. Immunofluorescence showed that focal
      adhesion plaques containing talin, vinculin and paxillin were most apparent in
      cells on PE grafted with PEG or BSA + C, and the fibres containing alpha-actin,
      beta-actin or SM1 and SM2 myosins were thicker, more numerous and more brightly
      stained in the cells on all modified PE samples than on pristine PE. An enzyme
      linked immunosorbent assay (ELISA) revealed increased concentrations of focal
      adhesion proteins talin and vinculin and also a cytoskeletal protein beta-actin
      in cells on PE modified with BSA + C. A contractile protein alpha-actin was
      increased in cells on PE grafted with PEG or Gly. These results showed that PE
      activated with plasma and subsequently grafted with bioactive molecules and
      colloidal C particles, especially with PEG and BSA + C, promotes the adhesion,
      proliferation and phenotypic maturation of VSMC.

PMID- 20057952
TI  - Effect of peptide-conjugated near-infrared fluorescent quantum dots (NIRF-QDs) on
      the invasion and metastasis of human tongue squamous cell carcinoma cell line
      Tca8113 in vitro.
AB  - In this study we investigated the effect of near-infrared fluorescent quantum
      dots (NIRF-QDs, QTracker) on the proliferation, adherence, invasion and
      chemotaxis of human tongue squamous cell carcinoma cell line Tca8113 in vitro.
      Cell proliferation and colony formation rate were determined by using a
      hemocytometer and culture plate. A transwell chamber assay was used to determine
      the cell invasion, adherence and chemotaxis. The results showed that there was no
      significant difference between the results of Tca8113 cells labeled with NIRF
      QD800 and those of unlabeled Tca8113 cells, suggesting that the proliferation,
      invasion, adherence and chemotaxis of Tca8113 cells were not affected by NIRF
      QD800. These results provide a basis for the further utilization of NIRF-QDs in
      non-invasive imaging and tracking of tumor cells in vivo.

PMID- 20057953
TI  - Role of the ubiquitin proteasome system in regulating skin pigmentation.
AB  - Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical
      rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded
      endogenously, at least in part, by the ubiquitin proteasome system (UPS). Several
      types of inherited hypopigmentary diseases, such as oculocutaneous albinism and
      Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of
      tyrosinase and its subsequent degradation which can occur due to the quality
      control machinery. Studies on carbohydrate modifications have revealed that
      tyrosinase in the endoplasmic reticulum (ER) is proteolyzed via ER-associated
      protein degradation and that tyrosinase degradation can also occur following its
      complete maturation in the Golgi. Among intrinsic factors that regulate the UPS,
      fatty acids have been shown to modulate tyrosinase degradation in contrasting
      manners through increased or decreased amounts of ubiquitinated tyrosinase that
      leads to its accelerated or decelerated degradation by proteasomes.

PMID- 20057951
TI  - ECM-based materials in cardiovascular applications: Inherent healing potential
      and augmentation of native regenerative processes.
AB  - The in vivo healing process of vascular grafts involves the interaction of many
      contributing factors. The ability of vascular grafts to provide an environment
      which allows successful accomplishment of this process is extremely difficult.
      Poor endothelisation, inflammation, infection, occlusion, thrombosis, hyperplasia
      and pseudoaneurysms are common issues with synthetic grafts in vivo. Advanced
      materials composed of decellularised extracellular matrices (ECM) have been shown
      to promote the healing process via modulation of the host immune response,
      resistance to bacterial infections, allowing re-innervation and reestablishing
      homeostasis in the healing region. The physiological balance within the newly
      developed vascular tissue is maintained via the recreation of correct biorheology
      and mechanotransduction factors including host immune response, infection
      control, homing and the attraction of progenitor cells and infiltration by host
      tissue. Here, we review the progress in this tissue engineering approach, the
      enhancement potential of ECM materials and future prospects to reach the clinical
      environment.

PMID- 20057956
TI  - Koln-Timisoara Molecular activity combined models toward interspecies toxicity
      assessment.
AB  - Aiming to provide a unified picture of computed activity - quantitative structure
      activity relationships, the so called Koln (ESIP
      ElementSpecificInfluenceParameter) model for activity and Timisoara (Spectral
      SAR) formulation of QSAR were pooled in order to assess the toxicity modeling and
      inter-toxicity correlation maps for aquatic organisms against paradigmatic
      organic compounds. The Koln ESIP model for estimation of a compound toxicity is
      based on the experimental measurement expressing the direct action of chemicals
      on the organism Hydractinia echinata so that the structural influence parameters
      are reflected by the metamorphosis degree itself. As such, the calculation of the
      structural parameters is absolutely necessary for correct evaluation and
      interpretation of the evolution of M(easured) and the C(computed) values. On the
      other hand, the Timisoara Spectral-SAR analysis offers correlation models and
      paths for H.e. species as well as for four other different organisms with which
      the toxicity may be inter-changed by means of the same mechanism of action
      induced by certain common chemicals.

PMID- 20057955
TI  - Robustness in regulatory interaction networks. A generic approach with
      applications at different levels: physiologic, metabolic and genetic.
AB  - Regulatory interaction networks are often studied on their dynamical side
      (existence of attractors, study of their stability). We focus here also on their
      robustness, that is their ability to offer the same spatiotemporal patterns and
      to resist to external perturbations such as losses of nodes or edges in the
      networks interactions architecture, changes in their environmental boundary
      conditions as well as changes in the update schedule (or updating mode) of the
      states of their elements (e.g., if these elements are genes, their synchronous
      coexpression mode versus their sequential expression). We define the generic
      notions of boundary, core, and critical vertex or edge of the underlying
      interaction graph of the regulatory network, whose disappearance causes dramatic
      changes in the number and nature of attractors (e.g., passage from a bistable
      behaviour to a unique periodic regime) or in the range of their basins of
      stability. The dynamic transition of states will be presented in the framework of
      threshold Boolean automata rules. A panorama of applications at different levels
      will be given: brain and plant morphogenesis, bulbar cardio-respiratory
      regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle
      and feather morphogenesis genetic control.

PMID- 20057957
TI  - In-TFT-array-process micro defect inspection using nonlinear principal component
      analysis.
AB  - Defect inspection plays a critical role in thin film transistor liquid crystal
      display (TFT-LCD) manufacture, and has received much attention in the field of
      automatic optical inspection (AOI). Previously, most focus was put on the
      problems of macro-scale Mura-defect detection in cell process, but it has
      recently been found that the defects which substantially influence the yield rate
      of LCD panels are actually those in the TFT array process, which is the first
      process in TFT-LCD manufacturing. Defect inspection in TFT array process is
      therefore considered a difficult task. This paper presents a novel inspection
      scheme based on kernel principal component analysis (KPCA) algorithm, which is a
      nonlinear version of the well-known PCA algorithm. The inspection scheme can not
      only detect the defects from the images captured from the surface of LCD panels,
      but also recognize the types of the detected defects automatically. Results,
      based on real images provided by a LCD manufacturer in Taiwan, indicate that the
      KPCA-based defect inspection scheme is able to achieve a defect detection rate of
      over 99% and a high defect classification rate of over 96% when the imbalanced
      support vector machine (ISVM) with 2-norm soft margin is employed as the
      classifier. More importantly, the inspection time is less than 1 s per input
      image.

PMID- 20057958
TI  - Electromagnetic biostimulation of living cultures for biotechnology, biofuel and
      bioenergy applications.
AB  - The surge of interest in bioenergy has been marked with increasing efforts in
      research and development to identify new sources of biomass and to incorporate
      cutting-edge biotechnology to improve efficiency and increase yields. It is
      evident that various microorganisms will play an integral role in the development
      of this newly emerging industry, such as yeast for ethanol and Escherichia coli
      for fine chemical fermentation. However, it appears that microalgae have become
      the most promising prospect for biomass production due to their ability to grow
      fast, produce large quantities of lipids, carbohydrates and proteins, thrive in
      poor quality waters, sequester and recycle carbon dioxide from industrial flue
      gases and remove pollutants from industrial, agricultural and municipal
      wastewaters. In an attempt to better understand and manipulate microorganisms for
      optimum production capacity, many researchers have investigated alternative
      methods for stimulating their growth and metabolic behavior. One such novel
      approach is the use of electromagnetic fields for the stimulation of growth and
      metabolic cascades and controlling biochemical pathways. An effort has been made
      in this review to consolidate the information on the current status of
      biostimulation research to enhance microbial growth and metabolism using
      electromagnetic fields. It summarizes information on the biostimulatory effects
      on growth and other biological processes to obtain insight regarding factors and
      dosages that lead to the stimulation and also what kind of processes have been
      reportedly affected. Diverse mechanistic theories and explanations for biological
      effects of electromagnetic fields on intra and extracellular environment have
      been discussed. The foundations of biophysical interactions such as
      bioelectromagnetic and biophotonic communication and organization within living
      systems are expounded with special consideration for spatiotemporal aspects of
      electromagnetic topology, leading to the potential of multipolar electromagnetic
      systems. The future direction for the use of biostimulation using
      bioelectromagnetic, biophotonic and electrochemical methods have been proposed
      for biotechnology industries in general with emphasis on an holistic biofuel
      system encompassing production of algal biomass, its processing and conversion to
      biofuel.

PMID- 20057960
TI  - Cellular interfacial and surface tensions determined from aggregate compression
      tests using a finite element model.
AB  - Although previous studies suggested that the interfacial tension gamma(cc) acting
      along cell-cell boundaries and the effective viscosity mu of the cell cytoplasm
      could be measured by compressing a spherical aggregate of cells between parallel
      plates, the mechanical understanding necessary to extract this information from
      these tests-tests that have provided the surface tension sigma(cm) acting along
      cell-medium interfaces-has been lacking. These tensions can produce net forces at
      the subcellular level and give rise to cell motions and tissue reorganization,
      the rates of which are regulated by mu. Here, a three-dimensional (3D) cell-based
      finite element model provides insight into the mechanics of the compression test,
      where these same forces are at work, and leads to quantitative relationships from
      which the effective viscosity mu of the cell cytoplasm, the tension gamma(cc)
      that acts along internal cell-cell interfaces and the surface tension sigma(cp)
      along the cell-platen boundaries can be determined from force-time curves and
      aggregate profiles. Tests on 5-day embryonic chick mesencephalon, neural retina,
      liver, and heart aggregates show that all of these properties vary significantly
      with cell type, except gamma(cc), which is remarkably constant. These properties
      are crucial for understanding cell rearrangement and tissue self-organization in
      contexts that include embryogenesis, cancer metastases, and tissue engineering.

PMID- 20057959
TI  - Application of Delta- and lambda-isomerism of octahedral metal complexes for
      inducing chiral nematic phases.
AB  - The Delta- and Lambda-isomerism of octahedral metal complexes is employed as a
      source of chirality for inducing chiral nematic phases. By applying a wide range
      of chiral metal complexes as a dopant, it has been found that tris(beta
      diketonato)metal(III) complexes exhibit an extremely high value of helical
      twisting power. The mechanism of induction of the chiral nematic phase is
      postulated on the basis of a surface chirality model. The strategy for designing
      an efficient dopant is described, together with the results using a number of
      examples of Co(III), Cr(III) and Ru(III) complexes with C(2) symmetry. The
      development of photo-responsive dopants to achieve the photo-induced structural
      change of liquid crystal by use of photo-isomerization of chiral metal complexes
      is also described.

PMID- 20057961
TI  - The local cell curvature guides pseudopodia towards chemoattractants.
AB  - Many eukaryotic cells use pseudopodia for movement towards chemoattractants. We
      developed a computer algorithm to identify pseudopodia, and analyzed how
      pseudopodia of Dictyostelium cells are guided toward cAMP. Surprisingly, the
      direction of a pseudopod is not actively oriented toward the gradient, but is
      always perpendicular to the local cell curvature. The gradient induces a bias in
      the position where the pseudopod emerges: pseudopodia more likely emerge at the
      side of the cell closer to the gradient where perpendicular pseudopodia are
      pointed automatically toward the chemoattractant. A mutant lacking the formin
      dDia2 is not spherical but has many invaginations. Although pseudopodia still
      emerge at the side closer to the gradient, the surface curvature is so irregular
      that many pseudopodia are not extended toward cAMP. The results imply that the
      direction of the pseudopod extension, and therefore also the direction of cell
      movement, is dominated by two aspects: the position at the cell surface where a
      pseudopod emerges, and the local curvature of the membrane at that position.

PMID- 20057962
TI  - Guided self-organization.

PMID- 20057963
TI  - Significance of cellular senescence in aging and cancer.
AB  - Cellular senescence is a mechanism that induces an irreversible growth arrest in
      all somatic cells. Senescent cells are metabolically active but lack the capacity
      to replicate. Evolutionary theories suggest that cellular senescence is related
      to the organismal decline occurring in aging organisms. Also, such theories
      describe senescence as an antagonistically pleiotropic process that can have
      beneficial or detrimental effect on the organism. Cellular senescence is believed
      to be involved in the cellular changes observed as aging progresses. Accumulation
      of senescent cells appears to occur widely as the organism ages. Furthermore,
      senescence is a key element of the tumor suppressor pathways. Therefore, it is
      part of the natural barrier against the uncontrolled proliferation observed in
      cellular development of malignancies in multicellular organisms. Activation of
      the senescence process guarantees a limited number of cellular replications. The
      genetic network led by p53 is responsible for activation of senescence in
      response to DNA damage and genomic instability that could lead to cancer. A
      better comprehension of the genetic networks that control the cell cycle and
      induce senescence is important to analyze the association of senescence to
      longevity and diseases related to aging. For these reasons, experimental research
      both in vitro and in vivo aims to develop anticancer therapies based on
      senescence activation. The last decade of research on role and function of
      senescence in aging and cancer are discussed in this paper.

PMID- 20057964
TI  - Docetaxel versus paclitaxel combined with 5-FU and leucovorin in advanced gastric
      cancer: combined analysis of two phase II trials.
AB  - PURPOSE: This is an ad hoc analysis of two phase II studies which compared the
      efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5
      fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND
      METHODS: Patients with advanced gastric adenocarcinoma who were untreated or had
      only received first-line chemotherapy, were treated with either paclitaxel (PFL;
      175 mg/m(2)) or docetaxel (DFL; 75 mg/m(2)) on day 1, followed by a bolus of LV
      (20 mg/m(2) days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m(2) days 1~3)
      every 3 weeks. The primary endpoint was overall response rate (ORR) and the
      secondary endpoint included survival and toxicity. RESULTS: Sixty-six patients
      received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received
      PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly
      different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of
      9.5 months, the progression free survival was 5.2 months (95% confidence interval
      [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL
      (p=0.17). The overall survival was also comparable between the patients who
      received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95%
      CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse
      event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non
      hematologic toxicities; specifically, grade >or=3 mucositis (5%) and diarrhea
      (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy
      (5%) were common in PFL. CONCLUSION: Thus, the two taxanes had similar efficacy
      in the treatment of advanced gastric cancer, but different toxicity profiles.
      Prospective comparative studies are required to further clarify the role of
      taxanes in the treatment of advanced gastric cancer.

PMID- 20057965
TI  - Biopsy related prostate status does not affect on the clinicopathological outcome
      of robotic assisted laparoscopic radical prostatectomy.
AB  - PURPOSE: To determine whether the biopsy core number and time interval between
      prostate biopsy and radical prostatectomy affect the operative and oncologic
      outcome of robot assisted laparoscopic radical prostatectomy (RALP). MATERIALS
      AND METHODS: From January 2008 to April 2009, a single surgeon performed 72 RALPs
      after an initial learning period of 30 cases. The relationship between time from
      biopsy to prostatectomy and biopsy core number with operative time and estimated
      blood loss (EBL) were initially evaluated with a linear regression model. These
      patients were classified into groups according to whether the interval from
      biopsy to RALP was within four weeks or not, and whether there were less than or
      greater than 10 core specimens removed. RESULTS: RALP was performed in 34
      patients within four weeks of biopsy, and in 38 patients more than 4 weeks after
      biopsy. According to the number of core specimens removed, less than 10 cores
      were performed in 10 patients, and more than 10 cores were performed in 62
      patients. Using an interval of 4 weeks as the cutoff point, early surgery was
      associated with longer operating time (232.6 vs 208.8 min) and increased
      estimated blood loss (305.1 vs 276.9 mL). For cases with more than 10 biopsy
      cores, there was a slight increase in operative time (229.2 vs 210.3 min). None
      of these differences were statistically significant by multivariate analysis.
      CONCLUSION: Our data suggests that there is no reason to delay RALP to more than
      4 weeks after prostate biopsy. It also revealed that the number of biopsy cores
      (up to 14) did not influence operative outcome. Thus, RALP is a feasible
      procedure regardless of the biopsy related prostate state.

PMID- 20057966
TI  - No association between promoter polymorphism of STK11 gene and lung cancer risk
      in the Korean population.
AB  - PURPOSE: Serine-threonine kinase11 (STK11) was originally identified in 1997 as
      the causative mutation that's responsible for Peutz-Jeghers Syndrome (PJS).
      Several recent studies have reported that the STK11 gene is an important human
      tumor suppressor gene in lung cancer. We evaluated the associations between the
      polymorphisms of the STK11 promoter region and the risk of lung cancer in 901
      Koreans. MATERIALS AND METHODS: By direct sequencing, we first discovered three
      novel polymorphisms (-1,795 T>C, -981 C>T and -160 G>T) and four known
      polymorphisms (-1,580 C>T, -1,494 A>C, -881 A>G and -458 G>C) of the STK11
      promoter region in 24 blood samples of 24 Korean lung cancer patients. Further
      genotype analyses were then performed on 443 lung cancer patients and 458
      controls. RESULTS: We discovered three novel polymorphisms and we identified four
      known polymorphisms of the STK11 promoter region in a Korean population.
      Statistical analyses revealed that the genotypes and haplotypes in the STK11 gene
      were not significantly associated with the risk of lung cancer in a Korean
      population. CONCLUSION: This is the first study that's focused on the association
      of STK11 promoter polymorphisms and the risk of lung cancer in a Korean
      population. To evaluate the role of the STK11 gene for the risk of lung cancer,
      the genotypes of the STK11 promoter region (-1,795 T>C, -1,494 A>C and -160 G>T)
      were determined in 901 Koreans, yet the result revealed no significant difference
      between the lung cancer patients and the controls. These results suggest that the
      three promoter polymorphisms we studied are not important risk factors for the
      susceptibility to lung cancer in Koreans.

PMID- 20057967
TI  - No association of vascular endothelial growth factor-A (VEGF-A) and VEGF-C
      expression with survival in patients with gastric cancer.
AB  - PURPOSE: Although the vascular endothelial growth factor (VEGF) superfamily has
      been identified to critically influence tumor-related angiogenesis, the
      prognostic significance of a VEGF expression in gastric cancer is still
      controversial. Accordingly, the present study analyzed the VEGF-A and VEGF-C
      expressions and their impact on the prognosis of patients with gastric cancer.
      MATERIALS AND METHODS: Three hundred seventy-five consecutive patients who
      underwent surgical resection for gastric adenocarcinoma with a curative intent
      were enrolled in the present study. Immunohistochemical staining for VEGF-A and
      VEGF-C was performed using the formalin fixed, paraffin embedded tumor tissues.
      RESULTS: Positive VEGF-A and VEGF-C expressions were observed in 337 (90.1%) and
      278 (74.9%) cases, respectively. The survival analysis showed that the expression
      of VEGF-A and VEGF-C had no effect on the OS and DFS. On the multivariate
      analysis that included age, gender and the TNM stage, no significant association
      between the grade of the VEGF-A or VEGF-C expression and survival was observed.
      CONCLUSION: The current study suggests that the tissue expression of VEGF-A or
      VEGF-C alone is not an independent prognostic marker for patients with surgically
      resected gastric adenocarcinoma.

PMID- 20057968
TI  - Mutational analysis of TTK gene in gastric and colorectal cancers with
      microsatellite instability.
AB  - PURPOSE: The TTK gene plays a crucial role in regulation of the mitotic
      checkpoint. The TTK gene has an A9 mononucleotide repeat in the coding sequences,
      which harbors mutations in gastric (GC) and colorectal cancers (CRC) with
      microsatellite instability (MSI). However, there are three more repeats (the A7s)
      in the coding sequences that have not been analyzed. The aim of this study was to
      explore whether the three A7s as well as the A9 are altered in GC and CRC, and to
      find any association of TTK mutation with clinocopathologic characteristics of GC
      and CRC. MATERIALS AND METHODS: We analyzed exon 5 (A7 and A7) and exon 22 (A9
      and A7) which have repeat sequences in 30 GC with high MSI (MSI-H), 15 GC with
      low MSI (MSI-L), 35 CRC with MSI-H, and 15 CRC with MSI-L, by single-strand
      conformation polymorphism (SSCP) and DNA sequencing assays. RESULTS: Overall, we
      detected 23 frameshift mutations in the repeat sequences of TTK in the GC with
      MSI-H (11/30; 36.7%) and the CRC with MSI-H (12/35; 34.3%), but not in the
      cancers with MSI-L. The mutations were observed in both A9 and A7 of exon 22, but
      in neither of the two A7s of exon 5. The mutations consisted of c.2560delA,
      c.2560dupA, c.2571delA and c.[2560delA(+)2571delA]. All of the mutations were
      frameshift mutations and would result in premature stops of TTK protein
      synthesis. There was no significant difference in clinopathologic parameters of
      the cancers with the mutations. CONCLUSION: Our data indicate that frameshift
      mutations of TTK are common in both GC and CRC with MSI-H, and that the mutations
      occur not only in the A9 repeat but also in the A7 repeat. The data suggest that
      frameshift mutations of TTK might alter cell cycle control in the affected cells
      and contribute to pathogenesis of cancers with MSI-H.

PMID- 20057969
TI  - Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma
      involving multiple lung metastases that was effectively treated with high-dose
      chemotherapy.
AB  - Choriocarcinoma in the testis is very rare, and it represents less than 1% (0.3%)
      of all the testicular germ cell tumors. It is a particularly aggressive variant
      of non-seminoma tumor, which is characterized by a high serum beta-HCG level and
      multiple lung metastases. The optimal management for this disease remains
      undefined. We report here on a case of choriocarcinoma with multiple lung
      metastases, and the patient has achieved continuous remission for 2 years after
      combination chemotherapy of BEP (bleomycin, etoposide and cisplatin) and
      sequential high-dose chemotherapy with autologous peripheral stem cell rescue.

PMID- 20057970
TI  - A case of desmoplastic small round cell tumor diagnosed in a young female
      patient.
AB  - Desmoplastic small round cell tumor is a very rare malignancy. We report the case
      of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2
      months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her
      disease as desmoplastic small round cell tumor using immunohistochemical
      staining, fluorescence in situ hybridization, and reverse transcriptase
      polymerase chain reaction. Because the mass invaded the pancreas and superior
      mesenteric vein as well as duodenum and the disease was disseminated to liver and
      peritoneum, she received palliative chemotherapy using vincristine, doxorubicin,
      cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy
      was stable disease. The patient expired 9 months after diagnosis.

PMID- 20057971
TI  - Pseudoaneurysm due to squamous cell carcinoma of the lung: two cases of
      spontaneous resolution after chemotherapy.
AB  - Pseudoaneurysm due to cancer is uncommon generally and is extremely rare in lung
      cancer. We report two cases of false aneurysms due to lung cancer that
      spontaneously regressed upon chemotherapy without intervention. Both patients had
      squamous cell carcinoma of the lung and the diagnosis of a pseudoaneurysm was
      made using computed tomography. There was no evidence of severe bronchial
      hemorrhage and the pseudoaneurysms were small and well-encased. Chemotherapy was
      performed and the pseudoaneurysms resolved.

PMID- 20057972
TI  - A case of spine origin chondroblastoma metastasis to lung.
AB  - Chondroblastoma is a rare benign cartilaginous neoplasm that accounts for
      approximately 1% of all bone tumors and characteristically arises in the
      epiphysis of a long bone, particularly the humerus, tibia, and femur.
      Chondroblastoma can affect people of all ages. It is, however, most common in
      children and young adults between the ages of 10 and 20 years. Although most
      chondroblastomas are cured by limited surgical procedures, occasional lesions
      behave more aggressively and may even metastasis. In this case a young man with
      pulmonary metastatic chondroblastoma on spine is presented. Unlike previously
      published examples of metastatic chondroblastoma, these metastasis developed
      before any operative manipulation of the primary tumor. And primary tumor site
      was also unusual. The histologic characteristics of the primary, metastatic
      tumors were those of a conventional chondroblastoma.

PMID- 20057973
TI  - Polymorphisms in the survivin promoter are associated with age of onset of
      ovarian cancer.
AB  - Survivin has been identified as an apoptosis inhibitor and a key regulator of
      mitosis. A common polymorphism (-31G>C) at the survivin promoter has been
      extensively studied in various cancers and reported to influence survivin
      expression. We hypothesize that polymorphisms in the survivin promoter are
      associated with clinical outcomes of patients with ovarian cancer. In this study,
      we genotyped all of five common and independent (r(2) < 0.25 for all LD) survivin
      promoter polymorphisms (-1547A/G [rs3764383], -644C/T [rs8073903], -625C/G
      [rs8073069], -241C/T [rs17878467], and -31G/C [rs9904341]) in 168 patients with
      primary epithelial ovarian cancer, using the polymerase chain reaction
      restriction fragment length polymorphism method. We found that -1547A/G and 
      31G/C were significantly associated with age of disease onset. Compared with
      patients with the -1547GG genotype, the -1547AA genotype showed a significantly
      younger age of disease onset (58.8 years vs. 70.1 years; P = 0.001); the -31CC
      genotype had a decrease, though not significant, in the age of disease onset,
      compared with patients with the -31GG genotype (57.1 years vs. 62.8 years; P =
      0.058). The numbers of -1547A and -31C alleles were associated with a decrease in
      age of onset in an allele-dose response manner (P(trend) = 0.001 and 0.026,
      respectively). However, no association was found between survivin polymorphisms
      and patients' prognosis, except for -625C/G SNP in 37 patients with a persistent
      disease. The findings suggest that the promoter variants of survivin may have an
      effect on age of onset of ovarian cancer. Validation studies with larger sample
      sizes are warranted.

PMID- 20057974
TI  - Caspase activation in transgenic mice with Alzheimer-like pathology: results from
      a pilot study utilizing the caspase inhibitor, Q-VD-OPh.
AB  - Despite the wealth of evidence supporting the activation of caspases in
      Alzheimer's disease (AD), chronic administration of a caspase inhibitor has never
      been tested in any animal model system. The purpose of the current report was to
      identify a suitable animal model that displays caspase activation and cleavage of
      critical proteins associated with AD, and secondly, to undertake a pilot study
      utilizing the novel caspase inhibitor, quinolyl-valyl-O-methylaspartyl-[-2, 6
      difluorophenoxy]-methyl ketone (Q-VD-OPh). Analysis of 12 month-old TgCRND8 mice,
      which represent an early-onset animal model for AD, indicated the activation of
      caspase-7 as well as the cleavage of tau and the amyloid precursor protein (APP).
      Having established that TgCRND8 mice represent a suitable model system to target
      caspases therapeutically, a prophylactic study was initiated utilizing Q-VD-OPh.
      Three month-old TgCRND8 mice were injected intraperitoneally three times a week
      for three months with 10 mg/kg Q-VD-OPh and compared to control mice injected
      with vehicle. Although there was no apparent effect on extracellular Abeta
      deposition, chronic treatment with Q-VD-OPh did prevent caspase-7 activation and
      limited the pathological changes associated with tau, including caspase cleavage.
      These preliminary findings suggest that further studies examining the utility of
      Q-VD-OPh as a potential therapeutic compound for the treatment of AD are
      warranted.

PMID- 20057975
TI  - Acid stress response of a mycobacterial proteome: insight from a gene ontology
      analysis.
AB  - Acidity in vesicles of macrophages is a general signal that bacteria respond to
      during infection. Mycobacteria are particularly capable of resisting the
      acidification in macrophages that engulf the bacteria. In this work, we used
      label-free quantitative proteomics to study the Mycobacterium smegmatis proteome
      under acid stress so as to gain an insight into the acidic adaptation in
      mycobacteria. We quantified 1032 proteins. With a 3-fold change threshold, 20 and
      52 proteins were found regulated at false discovery rates of 5% and 14%
      respectively. We performed a systems analysis based on gene ontology for the
      global proteome expression profile. We found that the most significant changes
      induced by the acid stress include a downregulation of transmembrane transporter
      activity and an upregulation of enzymes involved in fatty acid metabolism. The
      results suggest that reduced transmembrane transport and increased fatty acid
      metabolism probably contribute to or associate with acid tolerance in
      mycobacteria.

PMID- 20057976
TI  - Deciphering the MSG controversy.
AB  - Monosodium glutamate (MSG), a common flavor enhancer in various canned food and
      stereotypically associated with food in Chinese restaurants, has been claimed and
      tested to have side effects including headache and dizziness. However, the
      mechanism behind MSG-induced headache was not clear. Using dissociated mouse
      neuronal culture and cell injury assays, we determined whether incubation of
      neurons with clinically relevant concentrations of MSG induces cell swelling or
      death, and whether any measure can be taken to prevent or reduce MSG effects. We
      demonstrated that (1) Treatment with MSG induces a dose-dependent swelling and
      death of mature neurons (12-14 days in culture) with little effect on young
      immature neurons (<1 week in culture). The threshold concentration of MSG for
      neuronal injury is 3 microM; (2) MSG only injures neurons with little effect on
      glial cells; (3) Boiling MSG does not affect its toxicity but the addition of
      Vitamin C provides significant protection against MSG toxicity; (4) Pretreatment
      of neurons with a low dose of MSG reduces subsequent injury by a large dose of
      MSG. Together, our studies suggest that the side effect of MSG may be mediated,
      at least in part, by its toxic effect on brain neurons. Pre-exposure to low doses
      of MSG or the use of Vitamin C may prevent or reduce the side effects of MSG.

PMID- 20057977
TI  - Effects of erucic acid supplemented feeding on chronic doxorubucin toxicity in
      rats.
AB  - One of the undesired complications of the chemotherapy with doxorubicin is
      cardiotoxicity. Cardiac effect of erucic acid, which is a member of omega-9 fatty
      acid, is investigated on doxorubicin treatment in this study. Forty-eight rats
      were divided into eight groups and each group contained six rats. First group
      rats were fed with milk. In the third and fifth groups we fed rats with milk
      supplemented 0.5% and 5% erucic acid respectively. The groups 2, 4, 6 were fed as
      the groups 1, 3, 5 respectively; we injected 2 mg/kg twice weekly intraperitoneal
      doxorubicin to these groups whereas we injected isovolumous normal saline to the
      groups 1, 3, 5. Two other groups (groups 7 and 8) were fed with standard pellet.
      Group 8 received 2 mg/kg doxorubicin twice weekly; group 7 received normal
      saline. After 4 weeks hearts were isolated and mounted on a Langendorff apparatus
      perfused by modified Tyrode solution. Surviving rats were significantly less in
      erucic acid + doxorubicin groups at the end of the treatment period (p<0.05). No
      significant difference was found between groups for malondialdehyde, catalase,
      cytochrome c oxidase and isolated heart measurements. Concomitant application of
      erucic acid and doxorubicin showed profound toxicity.

PMID- 20057978
TI  - The effects of Fhit on tumorigenesis after multi-exposure to low-dose radiation.
AB  - Low-dose (</= 0.1 Gy) radiation could reduce high-dose induced damage including
      tumorigenesis. However, it remains unclear whether multi-exposure to low-dose
      radiation at a high dose rate has any risk for increasing tumorigenesis, and
      whether Fhit plays any role in the process. The purpose of this study is to
      investigate the effects of multi-exposure to low-dose radiation at a high dose
      rate on tumorigenesis, and the role of Fhit in it. We irradiated Fhit(+/+) and
      Fhit(-/-) mice with 1 Gy/1 or 0.1 Gy x 10 exposures at a dose rate of 1 Gy/min,
      sacrificed the mice at 1.5 years after radiation and observed multi-organ
      tumorigenesis. The results showed that although the spontaneous tumorigenesis in
      these mice was relatively high, 1 Gy/1-exposure dramatically increased the
      tumorigenesis including lung and liver tumor. Fhit(-/-) mice showed more
      tumorigenesis than Fhit(+/+) mice after 1 Gy/1-exposure. However, 0.1 Gy x 10
      exposures did not increase tumorigenesis, and there was no statistical difference
      in tumorigenesis between Fhit(+/+) mice and Fhit(-/-) mice following 0.1 Gy x 10
      exposures. Our results suggest that 0.1 Gy, even after multiple exposures, does
      not increase tumorigenesis, and Fhit could prevent high-dose radiation-induced
      tumors but has no effect in a low-dose environment.

PMID- 20057979
TI  - Continuous assessment of concentrations of cytokines in experimental injuries of
      the extremity.
AB  - Background. Inflammation plays an important part in the healing process. Little
      is known about the extent local inflammatory trauma response interacts with the
      central circulation and inflammation produced by central organs. The aim of the
      present study was to examine whether high cut-off microdialysis catheters offer
      potential to in real time assess interstitial cytokines variations in conjunction
      to markers of metabolism distal to a blunt vascular contusion. Methods. In a
      standardised contusion trauma model, microdialysis catheters (high MW (100kDa))
      were inserted in the gracilis muscle distal to the trauma for the local
      assessment of IL-6, IL-8, TNF-alpha, total protein and the metabolic mediators
      (glycerol, puruvate and lactate). The contra lateral uninjured leg served as
      control of the centrally mediated inflammation propagated to the extremities.
      Results. The trauma led to a significant and quantitatively large (8-10 fold)
      increase in inflammatory cytokines (IL6 and 8) as measured both in the injured
      and control legs. There was only a minor, and not significant increase in
      concentrations of cytokines in the injured leg compared to the control leg..
      There were no signs of ischemia in either leg. Conclusion. The new finding in
      this study is that both central, and local, inflammatory responses as well as
      metabolic mediators may be assessed continuously in skeletal muscle tissue distal
      to a major injury in an animal model. The findings suggest that the large trauma
      elicits a generalised inflammatory response to trauma rather than propagating a
      local one distal to the trauma.

PMID- 20057980
TI  - The development, optimization and validation of an assay for high throughput
      antiviral drug screening against Dengue virus.
AB  - Dengue virus (DENV) is listed as one of the NIAID Category A priority pathogens.
      Dengue disease is endemic in most tropical countries, with an estimated 2.5
      billion people living in areas at risk of DENV infection. Due to the lack of
      vaccines and antiviral drugs, it is now a huge public health burden around the
      world. In order to screen large compound libraries for the identification of
      novel antivirals targeting DENV, it is essential to develop a high throughput
      screening (HTS) amenable assay. Here, we present the development, optimization
      and validation of a cytopathic effect-based assay against Dengue virus serotype-2
      (DENV-2). The assay conditions, including cell culturing conditions, DMSO
      tolerance and the multiplicity of infection, were optimized in both 96- and 384
      well plates. Assay robustness and reproducibility were determined under the
      optimized conditions in 96-well plate, including Z'-value of 0.71, signal-to
      background ratio of 6.88, coefficient of variation of 6.3% in mock-infected cells
      and 12.3% in DENV-2 infected cells. This assay was further miniaturized into a
      384-well plate format with similar assay robustness and reproducibility comparing
      with these in the 96-well plate format. This assay was then validated using the
      LOPAC(1280) compound library, demonstrating its repeatability with comparable
      assay robustness and reproducibility. This fully developed and validated HTS
      amenable assay could be used in future studies to screen large compound libraries
      for the identification of novel antivirals against dengue disease.

PMID- 20057981
TI  - [Functional magnetic resonance imaging in psychiatry and psychotherapy].
AB  - technical improvements, functional magnetic resonance imaging (fMRI) has become
      the most popular and versatile imaging method in psychiatric research. The scope
      of this manuscript is to briefly introduce the basics of MR physics, the blood
      oxygenation level-dependent (BOLD) contrast as well as the principles of MR study
      design and functional data analysis. The presentation of exemplary studies on
      emotion recognition and empathy in schizophrenia patients will highlight the
      importance of MR methods in psychiatry. Finally, we will demonstrate insights
      into new developments that will further boost MR techniques in clinical research
      and will help to gain more insight into dysfunctional neural networks underlying
      cognitive and emotional deficits in psychiatric patients. Moreover, some
      techniques such as neurofeedback seem promising for evaluation of therapy effects
      on a behavioral and neural level.

PMID- 20057982
TI  - [Methodological problems with clinical functional MRI investigations].
AB  - During presurgical diagnostics clinical functional magnetic resonance imaging is
      increasingly being performed to improve the management of epilepsy and tumor
      patients. Rapid technical developments in fMRI technology continuously further
      new diagnostic applications. Safe clinical application requires a profound and
      critical handling of the various methodological problems inherent with this
      complex technique. This article reviews relevant problems and solutions for
      patient investigations up to the preparation of an individual clinical fMRI
      report.

PMID- 20057983
TI  - [GeSRU schedule for 2010].

PMID- 20057984
TI  - [Testosterone and erectile dysfunction].
AB  - Primary hypogonadism represents a classic but rare cause of erectile dysfunction
      (ED) in men. Therapy with testosterone as monotherapy is therefore unlikely to
      cure ED in the typical ED patient. However, recent developments indicate a much
      greater role of testosterone in erectile function than has been supposed in the
      past. Serum testosterone levels decline in men with increasing age. Aging men
      might develop late-onset hypogonadism (LOH) associated with characteristic
      symptoms. Typical symptoms of LOH are represented by decreased libido and sexual
      function, osteoporosis, altered distribution of body fat, overall reduction in
      physical strength, and alterations in the general mood. Experimental and clinical
      studies over the last few years have also pointed out that hypogonadism results
      in characteristic alterations of the erectile tissue of the penis. These
      alterations might be reversible in response to hormone therapy with testosterone.
      Particularly testosterone might be a helpful supportive therapy in cases where
      PDE-5 antagonists have tended to lose their effectiveness on the erectile tissue
      in the treatment of ED.

PMID- 20057985
TI  - [Testosterone - the central pivot of andrology].

PMID- 20057986
TI  - [A brief history of testosterone].
AB  - The history of testosterone is closely connected with the application of
      aphrodisiacs, research on sexual differentiation, and several therapies for
      rejuvenation around the year 1900. Chemical isolation and synthesis of androgens
      was achieved between 1931 and 1935 and only since then has clinically effective
      substitution therapy with testosterone for hypogonadism been available.

PMID- 20057987
TI  - [Testosterone and psyche].
AB  - Testosterone, like other steroid hormones, crosses the blood-brain barrier, and
      the androgen receptor is present in most parts of the human brain. Therefore,
      testosterone has many effects on the psyche, mainly in men but also in women.
      Most often discussed is its influence on sexuality, especially on desire and
      sexual fantasies, spontaneous nighttime erections, sexual activity, and the
      number of orgasms and ejaculations. Mood and energy are also testosterone
      related. Testosterone deficiency in male patients can lead to depressive
      disorders. In the past, elevated testosterone levels were seen as responsible for
      strongly aggressive behaviour. Some cognitive functions (spatial and mathematical
      sense, verbal skills) are, at least to a certain point, testosterone related. Due
      to the extremely complex functioning of the human brain, a scientifically exact
      statement regarding the true relationship between testosterone and human
      behaviour is not possible. On the one hand, the cause is definitively
      multifactorial, but on the other, testosterone is metabolised in the brain, and
      the metabolites act by themselves. Furthermore, a bidirectional relationship
      exists between hormones and human behaviour: Human behaviour is influenced by
      hormones, and human behaviour also has a direct influence on the levels of many
      hormones in the human body. Finally, much data in this field are derived from
      animal studies; studies on humans cannot be conducted because of ethical reasons
      or scientific and technical problems.

PMID- 20057988
TI  - [Testosterone replacement therapy for prostate cancer].
AB  - During the male 40s total testosterone levels decrease continuously. If clinical
      symptoms like decreasing libido, erectile dysfunction, osteoporosis, altered
      distribution of body fat, reduction in physical strength, or alterations in
      psychological mood are combined with a decreased serum testosterone level late
      onset hypogonadism (LOH) is obvious. Before the substitution of testosterone is
      initiated, it is essential to exclude prostate cancer because the progress of
      prostate cancer depends on androgens. The question is now how to treat patients
      who suffer from androgen deficiency but have cured prostate cancer in their
      history? Concerning this there are only a few studies with a small number of
      patients which show that testosterone substitution therapy is possible without an
      increased risk for recurrence of prostate cancer. As long as the patient was
      cured it does not matter if he underwent a radical prostatectomy or
      brachytherapy. Absolutely necessary is that the patient is well informed about
      the therapy and regularly controlled during the therapy.

PMID- 20057989
TI  - [Hormonal contraception for men: still a current issue].
AB  - The current status of hormonal contraception in men involves the principle of
      suppression of gonadotropins, LH, and FSH. This must be achieved as completely as
      possible to facilitate cessation of spermatogenesis and, thus, reach azoospermia.
      Simultaneously testosterone has to be replaced. Exogenous testosterone
      administration achieves the goal of gonadotropin suppression, but needs in
      addition the supplementation of a gestagen to fully suppress secretion of LH and
      FSH. Suppression of gonadotropins by steroids requires constant serum
      concentrations of sex steroids; hence, attempts using daily oral or transdermal
      preparations were, so far, unsuccessful. Thus, the immediate prospect for male
      contraception is not a"pill" itself but a regimen of combined injectable
      steroids, which are in advanced clinical testing.

PMID- 20057990
TI  - [Laboratory work-up of testosterone].
AB  - Measuring testosterone concentration is a central component of routine
      andrological diagnostics. To avoid complicated and often imprecise direct
      measurement of bioavailable testosterone, calculation by SHBG and albumin
      concentration is possible. When interpreting a measured testosterone
      concentration, numerous influencing factors have to be kept in mind. One main
      factor is circadian rhythm; furthermore, concentration decreases with advancing
      age. Changes of testosterone concentration can be caused by illness or the intake
      of specific drugs. The increase in SHBG concentration with age is of particular
      importance. Since internationally accepted standard values are missing,
      especially for elderly patients, their symptoms should always be considered when
      making a decision on hormone substitution.

PMID- 20057991
TI  - [Neurogenic or idiopathic destrusor overactivity after failed antimuscarinic
      treatment : clinical value of external temporary electrostimulation].
AB  - Antimuscarinic drugs are regarded as the standard treatment of detrusor
      overactivity (DO). However, side effects and lack of efficacy cause patients to
      discontinue long-term therapy. We evaluated the clinical efficacy of functional
      external electrostimulation (FES) as "second-line" therapy in patients with
      symptomatic idiopathic or neurogenic DO.In a retrospective study, 52 patients (38
      women and 14 men) were evaluated at least 1 year after FES. Eighteen patients
      (32.7%) regarded FES as successful. No change occurred in 34 patients (65.4%) and
      1 patient reported worsening of symptoms. Treatment success lasted for 13.2
      months. In successfully treated patients, voiding frequency was significantly
      reduced from 13.3/24 h to 6.1/24 h under FES and to 6.75/24 h at follow-up. FES
      is a clinically useful, well-tolerated, conservative second-line treatment option
      after failed antimuscarinic treatment in patients with idiopathic or neurogenic
      DO.

PMID- 20057992
TI  - [Male and female urinary incontinence from the viewpoint of the pelvic floor
      surgeon].

PMID- 20057994
TI  - The use of metformin in type 1 diabetes: a systematic review of efficacy.
AB  - AIMS/HYPOTHESIS: As adding metformin to insulin therapy has been advocated in
      type 1 diabetes, we conducted a systematic review of published clinical trials
      and clinical trial databases to assess the effects on HbA(1c), weight, insulin
      dose requirement and adverse effects. METHODS: We constructed evidence tables and
      fitted a fixed-effects model (inverse variance method) in order to assess
      heterogeneity between studies and give a crude measure of each overall treatment
      effect. RESULTS: Of 197 studies identified, nine involved randomisation with
      informed consent of patients with type 1 diabetes to metformin (vs placebo or
      comparator) in either a parallel or crossover design for at least 1 week. We
      noted marked heterogeneity in study design, drug dose, age of participants and
      length of follow-up. Metformin was associated with reductions in: (1) insulin
      dose requirement (5.7-10.1 U/day in six of seven studies); (2) HbA(1c) (0.6-0.9%
      in four of seven studies); (3) weight (1.7-6.0 kg in three of six studies); and
      (4) total cholesterol (0.3-0.41 mmol/l in three of seven studies). Metformin was
      well tolerated, albeit with a trend towards increased hypoglycaemia. Formal
      estimates of combined effects from the five trials which reported appropriate
      data indicated a significant reduction in insulin dose (6.6 U/day, p < 0.001) but
      no significant reduction in HbA(1c) (absolute reduction 0.11%, p = 0.42). No
      reported trials included cardiovascular outcomes. CONCLUSIONS/INTERPRETATION:
      Metformin reduces insulin-dose requirement in type 1 diabetes but it is unclear
      whether this is sustained beyond 1 year and whether there are benefits for
      cardiovascular and other key clinical outcomes.

PMID- 20057996
TI  - Reliability of clinical diagnosis in intraarticular hip diseases.
AB  - This study investigated the ability of experienced orthopedic surgeons to agree
      on a diagnosis of labral tear, femoroacetabular impingement (FAI), and capsular
      laxity using clinical examination. Eight patients under the care of an
      experienced hip arthroscopist underwent independent clinical evaluations by six
      orthopedic surgeons who specialized in management hip pain. No attempt was made
      to regulate the evaluation process as surgeons performed their examination as
      they would in their own practice. Average subject age was 27 years (19-47 years)
      with five females and three males. Subjects subsequently underwent arthroscopic
      surgery by the treating surgeon. Surgical findings were recorded with respect to
      the presence or absence of a labral tear, FAI, and/or capsular laxity. The
      percent agreement between the surgical findings and clinical examinations were
      determined. Surgical findings noted four subjects had a labral tear, five FAI,
      and three laxity. Based on clinical examination, surgeons agreed 63, 65 and 58%
      of the time with the surgical diagnosis of labral tear, FAI, and capsular laxity,
      respectively. The level of agreement did not seem to be dependent on the size or
      type of labral tear. Also, the ability to detect FAI did not seem to depend on
      whether the lesion was a cam, pincer, combined cam/pincer or size of the cam
      lesion. This study offers support that clinical examination techniques used for
      making a diagnosis needs to be improved and standardized if they are to be useful
      in diagnosing specific pathologies found with arthroscopic hip surgery.

PMID- 20057995
TI  - Year in review in Intensive Care Medicine  2009: I. Pneumonia and infections,
      sepsis,  outcome, acute renal failure and acid base,  nutrition and glycaemic
      control.

PMID- 20057997
TI  - Evaluation of tibial rotational alignment in total knee arthroplasty: a cadaver
      study.
AB  - Various techniques exist for establishing tibial rotational alignment during
      total knee arthroplasty (TKA). The purpose of this study is to establish the most
      precise and reproducible method to assess tibial component rotational alignment
      during TKA by comparing the flexion-extension technique (ROM) and the Posterior
      lateral Corner Locked Technique (PLCL). Twenty posterior stabilized TKAs were
      performed on cadavers. The rotation angles of the tibial components obtained
      using the two techniques were evaluated. The tibial component rotation axis
      obtained using the ROM technique and the PLCL method averaged, respectively, 0.35
      degrees (+ or - 4.2 degrees ) externally rotated and 0.34 degrees (+ or - 3
      degrees ) internally rotated to the Akagi line. No significant differences
      between the two methods were found and a high correlation exists between the two
      techniques (Pearson's coefficient = 0.88). The ROM and PLCL techniques are both
      precise and reproducible methods to assess tibial component rotation during TKA.
      However, while the ROM technique is dependent on the correct positioning of the
      femoral component and the soft tissue balancing, the PCLC method is easier if a
      complete visualization of the posterior-lateral corner of the cut tibial plateau
      is achieved.

PMID- 20057998
TI  - Excess mortality after pelvic fractures in institutionalized older people.
AB  - Mortality after pelvic fracture was calculated in residents of nursing homes.
      Compared with a matched comparison nonfracture group, excess mortality was found
      during the first 2 months after pelvic fracture. INTRODUCTION: Low energy pelvic
      fractures are mainly observed in people of advanced older age. The incidence of
      these fractures has increased considerably during the last decades. Information
      about excess mortality after pelvic fractures in older people is not available.
      METHODS: To calculate excess mortality, a retrospective cohort study was
      conducted. Data from residents institutionalized in Bavarian nursing homes
      between 2001 and 2006 were used. For each patient with a pelvic fracture
      (n=1,154), five residents without pelvic fracture (n=5,770) were matched by sex,
      age, date of admission to the nursing home, and level of care (measure for the
      need of care). Hazard regression models were applied. RESULTS: An excess
      mortality was found during the first months after pelvic fracture. In women, the
      increased mortality risk was limited to the first (hazard rate ratio (HR) 1.83,
      95% confidence interval (CI) 1.42-2.37) and second (HR 1.52, 95% CI 1.13-2.04)
      months after the injury. In men, excess mortality was more pronounced (HR 2.95,
      95% CI 1.57-5.54 for the first month) and appeared to last longer than in women.
      The majority of deaths due to pelvic fractures in the first 2 months after injury
      occurred following discharge from the hospital to the nursing home. CONCLUSION:
      Pelvic fractures are associated with an increased mortality. These results should
      encourage the development of preventive measures to reduce this excess mortality.

PMID- 20058000
TI  - L-forms and the unusual formation of progeny in cell wall-less   bacteria:
      recognizing the old roots of new science.

PMID- 20057999
TI  - Comparison of the effects of two resistance training regimens on muscular and
      bone responses in premenopausal women.
AB  - SUMMARY: A 28-week resistance training with linear periodization was compared
      with an undulating model in 27 premenopausal women. In both groups, bone mineral
      density (BMD) was not changed but muscle strength increased, and there were
      changes in anthropometrical and muscle damage parameters, indicating that in this
      population, these models are similar concerning these variables. INTRODUCTION:
      This study seeks to compare the effects of resistance training with undulating
      versus linear periodization on BMD, muscle strength, anthropometrical variables,
      and muscle damage parameters in premenopausal women. METHODS: Twenty-seven
      females (39.6 +/- 0.41 years, mean +/- standard error), without osteopenia or
      osteoporosis and without calcium supplementation, were randomly assigned either
      to a linear periodization group (LPG, n = 14) or to an undulating periodization
      group (UPG, n = 13). The subjects were trained three times a week for 28 weeks.
      Lumbar spine and femoral neck BMDs were measured through dual-energy X-ray
      absorptiometry. Maximal and submaximal dynamic muscle strengths were measured
      through the 1-RM and 20-RM tests, respectively. Anthropometrical (body mass,
      skinfolds, and perimeters) and muscle damage parameters were assessed through
      serum creatine kinase (CK) and delayed-onset muscle soreness (DOMS). RESULTS: BMD
      remained unchanged in both groups, despite significant increases in maximal (LPG,
      37-73%; UPG, 40-70%) and submaximal (LPG, 82-114%; UPG, 70-102%) muscle strength.
      The perimeter of the distal thigh was increased (about 1.7 cm) in both groups. CK
      and DOMS were greater in the first mesocycle than in the subsequent ones. After
      the 1st training session in each mesocycle, 24 and 48 h CK was increased as
      compared to pretraining values. CONCLUSIONS: The resistance training of 28 weeks
      increased muscle strength in both training groups with no difference in BMD or in
      the occurrence of muscle damage.

PMID- 20058001
TI  - MRI of the transverse and alar ligaments in rheumatoid arthritis: feasibility and
      relations to atlantoaxial subluxation and disease activity.
AB  - INTRODUCTION: Dysfunctional transverse and alar craniovertebral ligaments can
      cause instability and osseous destruction in rheumatoid arthritis (RA). This
      study examined (1) the feasibility of high-resolution magnetic resonance imaging
      (MRI) of these ligaments in RA and (2) the relation between ligament high-signal
      changes and atlantoaxial subluxation and RA duration/severity. METHODS:
      Consecutive RA patients (n=46) underwent clinical examination, functional
      radiography, and high-resolution MRI. Two blinded radiologists rated MRI image
      quality, graded ligament high-signal changes 0-3 on proton-weighted sequences
      using an existing grading system, and assessed cervical spine rheumatic changes
      on short tau inversion recovery images. Agreement was analyzed using kappa and
      relations using multiple logistic regression. RESULTS: MRI images had good
      quality in 42 (91.3%) of 46 patients and were interpretable in 44 (32 women and
      12 men, median age/disease duration 60.4/9.1 years). MRI grades 2-3 changes of
      the transverse and alar ligaments showed moderate and good interobserver
      agreement (kappa 0.59 and 0.78), respectively, and prevalence 31.8% and 34.1%.
      Such ligament changes were more frequent with increasing anterior atlantoaxial
      subluxation (p=0.012 transverse, p=0.028 alar), higher erythrocyte sedimentation
      rate (p=0.003 transverse), positive rheumatoid factor (p=0.002 alar), and neck
      pain (p=0.004 alar). CONCLUSION: This first study of high-resolution MRI of these
      ligaments in RA showed high feasibility and relations with atlantoaxial
      subluxation, RA disease activity, and neck pain. The clinical usefulness of such
      MRI needs further evaluation.

PMID- 20058002
TI  - Predicting the bioavailability of sediment-associated spiked compounds by using
      the polyoxymethylene passive sampling and tenax extraction methods in sediments
      from three river basins in Europe.
AB  - This study presents the bioavailability of four spiked compounds to Lumbriculus
      variegatus, in sediment samples from three river basins in Europe: the Elbe, the
      Llobregat, and the Scheldt. Twenty sediment samples differing in physical and
      chemical properties were spiked with chlorpyrifos, pyrene, tetrachloribiphenyl,
      and tetrabromo diphenyl ether. The main focus of this study was to compare the
      suitability of two chemical approaches-the rapidly desorbing fraction method
      based on the Tenax extraction and the freely dissolved chemical concentration
      method based on polyoxymethylene passive sampling-for predicting the
      bioavailability of sediment-associated hydrophobic compounds. It appears that
      accessible concentration estimated by Tenax extraction does not result in equal
      freely dissolved concentrations based on polyoxymethylene passive sampling
      results. The present data show that freely dissolved concentration in pore water
      mainly determines the uptake by organisms and, therefore, the polyoxymethylene
      passive sampling method was a successful approach to estimating the
      bioavailability of sediment-associated lipophilic contaminants (log octanol-water
      partitioning coefficient >6). The sediment characteristics or river basin
      differences had only a minor effect on the bioavailability estimates. Overall,
      passive samplers have not been tested to a sufficient extent in various chemicals
      or exposure matrixes. For this reason, bioassays are still needed in the risk
      assessment process in order to verify results based on passive sampling methods.

PMID- 20058003
TI  - Major histocompatibility complex variation and evolution  at a single, expressed
      DQA locus in two genera of elephants.
AB  - Genes of the vertebrate major histocompatibility complex (MHC) are crucial to
      defense against infectious disease, provide an important measure of functional
      genetic diversity, and have been implicated in mate choice and kin recognition.
      As a result, MHC loci have been characterized for a number of vertebrate species,
      especially mammals;however, elephants are a notable exception. Our study is the
      first to characterize patterns of genetic diversity and natural selection in the
      elephant MHC. We did so using DNA sequences from a single, expressed DQA locus in
      elephants.We characterized six alleles in 30 African elephants(Loxodonta
      africana) and four alleles in three Asian elephants (Elephas maximus). In
      addition, for two of the African alleles and three of the Asian alleles, we
      characterized complete coding sequences (exons 1-5) and nearly complete non
      coding sequences (introns 2-4) for the class II DQA loci. Compared to DQA in
      other wild mammals, we found moderate polymorphism and allelic diversity and
      similar patterns of selection; patterns of non-synonymous and synonymous
      substitutions were consistent with balancing selection acting on the peptides
      involved in antigen binding in the second exon. In addition, balancing selection
      has led to strong trans-species allelism that has maintained multiple allelic
      lineages across both genera of extant elephants for at least 6 million years. We
      discuss our results in the context of MHC diversity in other mammals and patterns
      of evolution in elephants.

PMID- 20058004
TI  - Transarterial thrombin injection secured with an embolic protection device as a
      treatment for a superior mesenteric artery pseudoaneurysm.
AB  - A pseudoaneurysm of the superior mesenteric artery (SMA) is a rare and life
      threatening condition of various etiology. Even unruptured it can cause severe
      health problems or death. We report a 71-year-old male with a SMA pseudoaneurysm
      who was successfully treated with a transarterial thrombin injection secured with
      an embolic protection device used in carotid angioplasty. To our knowledge, this
      is the first case of a SMA pseudoaneurysm treated by this method.

PMID- 20058005
TI  - Value of preoperative superselective embolization of the isthmus in a patient
      with upper urinary tract urothelial carcinoma and horseshoe kidney.
AB  - Standard treatment for upper urinary tract urothelial carcinoma (UUTUC) implies
      the radical removal of all urothelium-lined tissue, which requires
      nephroureterectomy with bladder cuff removal. We report on a patient with a rare
      coincidence of UUTUC and horseshoe kidney in whom a preoperative angiography
      helped to identify and subsequently embolize an abberant isthmic feeding artery,
      which was located in between both collecting systems. Ischemic discoloration of
      the isthmus area facilitated resection and no major blood loss occurred.
      Preoperative superselective embolization of the isthmus as the renal split area
      can be an effective tool to facilitate nephroureterectomy in the case of a
      horseshoe kidney.

PMID- 20058006
TI  - Radiological management of hemoptysis: a comprehensive review of diagnostic
      imaging and bronchial arterial embolization.
AB  - Hemoptysis can be a life-threatening respiratory emergency and indicates
      potentially serious underlying intrathoracic disease. Large-volume hemoptysis
      carries significant mortality and warrants urgent investigation and intervention.
      Initial assessment by chest radiography, bronchoscopy, and computed tomography
      (CT) is useful in localizing the bleeding site and identifying the underlying
      cause. Multidetector CT angiography is a relatively new imaging technique that
      allows delineation of abnormal bronchial and nonbronchial arteries using
      reformatted images in multiple projections, which can be used to guide
      therapeutic arterial embolization procedures. Bronchial artery embolization (BAE)
      is now considered to be the most effective procedure for the management of
      massive and recurrent hemoptysis, either as a first-line therapy or as an adjunct
      to elective surgery. It is a safe technique in the hands of an experienced
      operator with knowledge of bronchial artery anatomy and the potential pitfalls of
      the procedure. Recurrent bleeding is not uncommon, especially if there is
      progression of the underlying disease process. Prompt repeat embolization is
      advised in patients with recurrent hemoptysis in order to identify nonbronchial
      systemic and pulmonary arterial sources of bleeding. This article reviews the
      pathophysiology and causes of hemoptysis, diagnostic imaging and therapeutic
      options, and technique and outcomes of BAE.

PMID- 20058007
TI  - Preoperative portal vein embolization tailored to prepare the liver for complex
      resections: initial experience.
AB  - The purpose of this study was to evaluate the safety and efficacy of preoperative
      portal vein embolization (PVE) tailored to prepare the liver for complex and
      extended resections. During the past 5 years, 12 PVEs were performed in
      noncirrhotic patients with liver metastases from colon cancer (n = 10), choroidal
      melanoma (n = 1), and leiomyosarcoma (n = 1) to prepare complex anatomical liver
      resections in patients with small future remnant livers. These liver resections
      planned to preserve only segment IV in four patients, segments IV, V, and VIII in
      four patients, segments II, III, VI, and VII in three patients, and segments V
      and VI in one patient. PVE was performed under general anesthesia with a flow
      guided injection of a mixture of cyanoacrylate and Lipiodol using a 5-Fr
      catheter. All portal branches feeding the liver segments to be resected were
      successfully embolized with cyanoacrylate except one, which was occluded with
      coils due to the risk of reflux with cyanoacrylate. After a mean of 32 days, CT
      volumetry revealed a mean hypertrophy of the unembolized liver of 47 +/- 25%
      (range, 21-88%). Liver resections could be performed in 10 patients but were
      canceled in 2, due to the occurrence of a new hepatic tumor in one and an
      insufficiently increased volume in the other. Among the 10 patients who underwent
      the liver resection, 1 died of postoperative sepsis, 3 died 3 to 32 months after
      surgery, including 1 death unrelated to cancer, and 6 were alive after 6 to 36
      months after surgery. In conclusion, in this preliminary report, PVE appears to
      be feasible and able to induce hypertrophy of the future remnant liver before a
      complex and extended hepatectomy. Further evaluation is needed in a larger
      cohort.

PMID- 20058008
TI  - Main bile duct stricture occurring after transcatheter arterial chemoembolization
      for hepatocellular carcinoma.
AB  - The purpose of this study was to evaluate the clinical course of main bile duct
      stricture at the hepatic hilum after transcatheter arterial chemoembolization
      (TACE) for hepatocellular carcinoma (HCC). Among 446 consecutive patients with
      HCC treated by TACE, main bile duct stricture developed in 18 (4.0%). All imaging
      and laboratory data, treatment course, and outcomes were retrospectively
      analyzed. All patients had 1 to 2 tumors measuring 10 to 100 mm in diameter (mean
      +/- SD 24.5 +/- 5.4 mm) near the hepatic hilum fed by the caudate arterial branch
      (A1) and/or medial segmental artery (A4) of the liver. During the TACE procedure
      that caused bile duct injury, A1 was embolized in 8, A4 was embolized in 5, and
      both were embolized in 5 patients. Nine patients (50.0%) had a history of TACE in
      either A1 or A4. Iodized oil accumulation in the bile duct wall was seen in all
      patients on computed tomography obtained 1 week later. Bile duct dilatation
      caused by main bile duct stricture developed in both lobes (n = 9), in the right
      lobe (n = 3), in the left lobe (n = 4), in segment (S) 2 (n = 1), and in S3 (n =
      1). Serum levels of alkaline phosphatase and gamma-glutamyltranspeptidase
      increased in 13 patients. Biloma requiring drainage developed in 2 patients;
      jaundice developed in 4 patients; and metallic stents were placed in 3 patients.
      Complications after additional TACE sessions, including biloma (n = 3) and/or
      jaundice (n = 5), occurred in 7 patients and were treated by additional
      intervention, including metallic stent placement in 2 patients. After initial
      TACE of A1 and/or A4, 8 patients (44.4%), including 5 with uncontrollable
      jaundice or cholangitis, died at 37.9 +/- 34.9 months after TACE, and 10 (55.6%)
      have survived for 38.4 +/- 37.9 months. Selective TACE of A1 and/or A4 carries a
      risk of main bile duct stricture at the hepatic hilum. Biloma and jaundice are
      serious complications associated with bile duct strictures.

PMID- 20058009
TI  - Voreloxin, a first-in-class anticancer quinolone derivative, acts synergistically
      with cytarabine in vitro and induces bone marrow aplasia in vivo.
AB  - MAIN PURPOSE: Voreloxin is a first-in-class anticancer quinolone derivative that
      intercalates DNA and inhibits topoisomerase II, inducing site-selective DNA
      damage. Voreloxin is in clinical studies, as a single agent and in combination
      with cytarabine, for the treatment of acute myeloid leukemia (AML). The
      preclinical studies reported here were performed to investigate the activity of
      voreloxin alone and in combination with cytarabine, in support of the clinical
      program. RESEARCH QUESTIONS: Is single agent voreloxin active in preclinical
      models of AML? Does the combination of voreloxin and cytarabine enhance the
      activity of either agent alone? METHODS: Inhibition of proliferation was studied
      in three cancer cell lines: HL-60 (acute promyelocytic leukemia), MV4-11 (AML),
      and CCRF-CEM (Acute lymphoblastic leukemia). Combination index (CI) analysis
      established the effect of the drugs in combination. A mouse model of bone marrow
      ablation was used to investigate in vivo efficacy of the drugs alone and in
      combination. Peripheral white blood cell and platelet counts were followed to
      assess marrow impact and recovery. RESULTS: Voreloxin and cytarabine alone and in
      combination exhibited cytotoxic activity in human leukemia cell lines and in
      vivo. The two drugs had additive or synergistic activity in vitro and supra
      additive activity in vivo. Bone marrow ablation was accompanied by reductions in
      peripheral white blood cells and platelets that were reversible within 1 week,
      consistent with the AML treatment paradigm. CONCLUSIONS: These data support
      ongoing clinical evaluation of voreloxin both alone and in combination with
      cytarabine for the treatment of AML.

PMID- 20058010
TI  - Tongue infarction as first symptom of temporal arteritis.
AB  - Giant cell arteritis (GCA) is the most common systemic vasculitis affecting
      people over 50 years. This disease is a diagnostic challenge with a range of
      clinical symptoms and findings due to different affected vessels. Because of
      this, the initial diagnosis can be tricky, and some of the patients present at
      first time with a real unusual initial manifestation. One of these can be tongue
      necrosis, which is according to the literature in accordance with scalp necrosis,
      the rarest initial manifestation of GCA We describe a patient who presented with
      tongue necrosis as initial symptom of GCA. The belated diagnose resulted in
      subtotal necrosis of the mobile part of the tongue.

PMID- 20058011
TI  - Asymmetrical hemochromatosis arthropathy in a patient with a history of
      poliomyelitis.
AB  - Herein, we report a case of a 67-year-old man with hereditary hemochromatosis and
      a history of poliomyelitis that had caused a paresis of the right arm.
      Hemochromatosis-associated arthropathy developed in all but the paretic limb. X
      ray and MRI revealed degenerative, massive inflammatory and destructive changes
      in the joints of the non-paretic hand only. These findings argue for the
      contribution of physical exposure and non-mechanical factors to the development
      of the hemochromatosis arthropathy.

PMID- 20058012
TI  - Malignancy in scleroderma patients from south west England: a population-based
      cohort study.
AB  - The pathophysiological relationship between scleroderma and malignancy remains
      poorly understood. Although some previous studies have demonstrated an increased
      malignancy risk in patients with scleroderma, others have been inconclusive. We
      aimed to determine if patients with scleroderma had an increased risk of
      malignancy compared to an age- and sex-matched local South West England
      population, and if there were any important differences between scleroderma
      patients with and without malignancy. Methods of this study are as follows. Notes
      were obtained on all local scleroderma patients (n = 68) locally, and those
      diagnosed with malignancy verified by contacting each patient's general
      practitioner. Expected malignancy figures were obtained from age- and sex
      stratified regional prevalence data provided by the South West Cancer
      Intelligence Service registry. Among the patients, 22.1% with scleroderma were
      identified with concurrent malignancy. Affected sites were of the breast (n = 5),
      haematological system (n = 5), skin (n = 4), and unknown primary (n = 1).
      Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95%
      CI 1.77-5.20, p = 0.01). In particular, this risk was the highest for
      haematological malignancies (RR = 18.5, 95% CI 6-43, p = 0.03), especially for
      non-Hodgkin's lymphoma (RR = 25.8, 95% CI 5-75, p = 0.10). The majority of
      patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9
      years). Age of >70 and patients with limited scleroderma were significant risk
      factors for a patient with scleroderma to have a concurrent malignancy; however,
      no increased risk was found in patients with any particular pattern of organ
      involvement, cytotoxic usage or serology. To conclude, in this small patient
      cohort, we have found that scleroderma is associated with an increased risk of
      malignancy. This risk is statistically significant in patients with limited
      scleroderma. Patients who are elderly and those with limited disease should be
      closely scrutinized at follow-up appointments.

PMID- 20058013
TI  - Successful treatment of steroid and cyclophosphamide-resistant diffuse
      scleroderma-associated interstitial lung disease with rituximab.
AB  - Scleroderma (SSc) is a multisystem disorder characterized by fibrosis and
      collagen deposition in the dermis, but affects multiple organ systems, leading to
      esophageal dysmotility, renal failure, and interstitial lung disease (ILD). ILD
      is common manifestation of diffuse type of SSc and may be life threatening, and
      require aggressive therapy with cytotoxic agents. Although high-dose steroid and
      cyclophosphamide are most commonly used therapy for SSc-associated ILD, the
      efficacy is questionable in some cases and more effective and less toxic
      therapies are needed. Rituximab (RTX) is a chimeric mAb against human CD20 that
      depletes peripheral B cells and introduced for systemic rheumatic diseases.
      However, there were no enough evidences for SSc-associated ILD. We report herein
      a case of 47-year-old female with diffuse type of SSc with steroid and
      cyclophosphamide-resistant ILD that was successfully treated with RTX. Thus, we
      suggested that RTX could be an efficacious therapeutic modality for severe,
      conventional treatment-resistant SSc-associated ILD.

PMID- 20058014
TI  - Influence of gender on the clinical and laboratory spectra of patients with
      primary antiphospholipid syndrome.
AB  - The objectives of this cross-sectional study were to evaluate the differences
      between males and females in the clinical and biochemical manifestations of
      primary antiphospholipid antibody syndrome (PAPS). The method involved 49
      patients (38 premenopausal females and 11 males) diagnosed with PAPS (according
      to the Sapporo criteria) and their demographic data, clinical data, medications
      used and antiphospholipid antibodies were analyzed. The results of this study are
      as follows. Both the groups of patients were statistically similar regarding age,
      race, weight and body mass index. However, males were significantly taller than
      females (172 +/- 8.9 vs. 159.2 +/- 6.2 cm, p < 0.0001). The duration of disease
      was similar for females and males. The prevalence of pulmonary thromboembolism
      was higher in females than in males (34.2 vs. 0.0%, p = 0.024). Regarding other
      PAPS manifestations (arterial events, venous events, deep venous thrombosis,
      thrombocytopenia, acute myocardial infarction, angina, cerebrovascular accidents
      and Sneddon syndrome), comorbidities (arterial hypertension and dyslipidemia),
      lifestyle (physical activity, previous smoking and current smoking) and the use
      of medications (current and previous use of corticosteroids, as well as the use
      of statins or chloroquine), both groups were statistically similar (p > 0.05).
      More females than males tested positive for IgM anticardiolipin antibodies (76.3
      vs. 36.4%, p = 0.025) or for at least one of the antiphospholipid antibodies
      tested (either IgM anticardiolipin or IgG anticardiolipin 84.2 vs. 45.5%, p =
      0.016). However, both groups were similar regarding the frequency of positivity
      for lupus anticoagulant and isolated IgG anticardiolipin, as well as regarding
      mean levels of IgG and IgM anticardiolipin (p > 0.05). We concluded that, among
      PAPS patients, the frequency of pulmonary thromboembolism and of positivity for
      IgM anticardiolipin is higher in females than in males. Our findings show that
      there are gender differences in PAPS, differences that might be related to
      alterations in sex hormones.

PMID- 20058015
TI  - Is rheumatoid factor still a superior test for the diagnosis of rheumatoid
      arthritis?
AB  - The diagnosis of rheumatoid arthritis (RA) is based primarily on the 1987 revised
      American College of Rheumatology criteria for RA, which considers mainly the
      clinical symptoms. But typical clinical symptoms of RA are not manifested
      completely in early disease course. On the other hand, appreciable advantages
      have been made in the therapeutic strategy of RA in the last decade and highly
      effective disease-modifying anti-rheumatic drugs are available now for the
      control of RA. The treatment strategy for the control of early RA is aggressive.
      Thus, a highly specific and early diagnostic marker is needed for the detection
      of RA. Our study is an attempt to see the role of anti-CCP2 antibody (claimed to
      be highly specific and early diagnostic tool) in the diagnosis of RA. We studied
      119 cases of RA in terms of clinical symptoms, disease duration and various
      autoantibody [including rheumatoid factor (RF), anti-CCP2 antibody, antinuclear
      antibody, anti-dsDNA] and C-reactive protein status. All the tests were also
      performed in 26 age and sex-matched healthy controls. Estimation of antibodies
      was done by quantitative ELISA. IgM RF was positive in 47.89% cases (p value =
      0.000), followed by IgG RF (42.01%, p = 0.000) and IgA RF (36.97%, p = 0.000). RF
      was positive in 64.7% RA cases (p value = 0.000) when all three isotypes were
      tested together. RF was also detected in one healthy control. In 92 cases, anti
      CCP2 Ab was done, hence other data were analyzed further in 92 cases only. Anti
      CCP2 Ab was positive (cut-off = 15.0 U/ml) in only 50% RA patients but none of
      the healthy controls was positive for it. Swelling of joints was seen in 82.6%
      anti-CCP2 Ab positive cases (p value = 0.092) when compared with anti-CCP2 Ab
      negative cases (67.4%) while among RF positive cases, only 65.4% ((p value =
      0.010) cases had swelling of joints. Out of 39 RA cases presenting with disease
      duration less than 1 year, only 48.71% patients were anti-CCP2 Ab positive while
      RF was positive in 61.53% patients. Utility of various combined autoantibody
      tests revealed that if one does all isotypes of RF (IgG, IgA and IgM) only, then
      64.7% RA cases can be diagnosed and if anti-CCP2 Ab is added to it, the
      sensitivity increases to 75.56%. Thus, our study concludes that anti-CCP2 Ab is
      not a sensitive test for the diagnosis of RA neither it is useful in early
      diagnosis of RA, but it increases the sensitivity if added with all RF isotypes.

PMID- 20058016
TI  - Cardiac remodeling and effects on exercise capacity after interventional closure
      of atrial septal defects in different adult age groups.
AB  - BACKGROUND: Interventional closure of atrial septal defects (ASD) has become a
      standard procedure in pediatric and adult patients. We report immediate and mid
      term results in different adult age groups. METHODS: A retrospective analysis of
      332 patients undergoing percutaneous ASD closure between 1998 and 2008 was
      performed. Beside echocardiographic and hemodynamic measurements, the NYHA
      functional class was assessed before and after ASD closure. The peak oxygen
      uptake (VO(2peak)) was available in a subgroup of 154 patients. RESULTS: The
      different age groups did not differ significantly in shunt volume or defect
      diameter, but a significant increase could be detected in mean pulmonary arterial
      pressure, mean left atrial pressure and pulmonary vascular resistance (PVR9 with
      increasing age). Right ventricular enlargement was present in all age groups, but
      the degree of enlargement increased with age. Transcatheter ASD closure was
      successful in 99.4%, major adverse events occurred in four patients (1.2%). At 3
      months from closure, 123 patients reported an improvement, 7 of worsening and 163
      of no change in their functional capacity. A significant increase in VO(2peak)
      could be registered in all subgroups after ASD closure. When classified by shunt
      volume no change could be detected in VO(2peak) in the patients with a Q(p):Q(s)
      < 2, whereas patients with a Q(p):Q(s) > 2 had a highly significant VO(2peak)
      increase. CONCLUSION: Patients benefit from interventional closure of
      hemodynamically significant ASD regardless of their age. However, the defect
      should be repaired as early as possible to prevent hemodynamic complications,
      such as the development of pulmonary hypertension and cardiac arrhythmias.

PMID- 20058017
TI  - Percutaneous cervical nucleoplasty and percutaneous cervical discectomy
      treatments of the contained cervical disc herniation.
AB  - BACKGROUND: There were no studies in literature to compare the clinical outcomes
      of percutaneous nucleoplasty (PCN) and percutaneous cervical discectomy (PCD) in
      contained cervical disc herniation. METHODS: A retrospective of patients with
      symptomatic contained cervical disc herniated were operated on with PCN and PCD
      from June 2003 to July 2005. Two-hundred and four patients initially fulfilled
      the study criteria, and 28 patients were lost in follow-up. The patients were
      categorized into different groups depending on the procedure by PCN (81 cases) or
      PCD (95 cases). RESULTS: The clinical outcomes, pain reduction, and segment
      stability were recorded during this study. Puncture of the needle into the disc
      space was accurately performed under C-arm fluoroscopy guidance in all cases and
      no intraoperative deaths were reported in our study. At the end, 176 cases had
      follow-up and 28 cases were lost, and the follow-up rate was 88.0% (81/92) in the
      PCN group and 84.8% (95/112) in the PCD group. The follow-up time ranged from 16
      to 48 months (average 29 months), and on an average of 28.86 +/- 4.52 months on
      PCN and 8.42 +/- 3.21 months on PCD (t = -0.24, P = 0.81, >0.05). The operation
      time averages of PCN and PCD are 4.67 +/- 1.16 and 11.95 +/- 1.80, respectively
      (P < 0.01). The pain index improved from 7.12 +/- 1.13 to 2.74 +/- 0.89 (t =
      27.03, P = 0.0000, <0.001) in PCN patients and from 7.18 +/- 1.09 to 2.71 +/-
      0.91 (t = 29.57, P = 0.0000, <0.001) in PCD patients. Clinical results of PCN
      were excellent in 31 cases, good 32 cases, fair 13 cases, and poor 5 cases; for
      PCD, the results were 33, 42, 12, and 7 cases, respectively, and 1 in discitis.
      Good and excellent was 78.4% (77.8% in PCN and 79.5% in PCD, P > 0.05). There was
      one case of PCN that had the partial Perc-D SpineWand broken in the disc space,
      cannot be moved by the percutaneous cervical discectomy, and remained there
      itself. One of the cases had discitis in this study after PCD. Patient presented
      with neck pain and associated radicular pain and numbness in the left upper-limb
      after 8 days of PCD. There were no instable cases after procedures of PCN and
      PCD. There were no significant difference in stability of preoperatively and
      postoperatively between PCN and PCD (P > 0.05). CONCLUSIONS: PCN and PCD
      treatments of contained cervical disc herniation show good outcomes and there was
      no difference in the stability of cervical spine. PCN and PCD are safe, minimally
      invasive, and no differences were observed between the methods in clinical
      outcome.

PMID- 20058018
TI  - T1rho and T2rho MRI in the evaluation of Parkinson's disease.
AB  - Prior work has shown that adiabatic T(1rho) and T(2rho) relaxation time constants
      may have sensitivity to cellular changes and the presence of iron, respectively,
      in Parkinson's disease (PD). Further understanding of these magnetic resonance
      imaging (MRI) methods and how they relate to measures of disease severity and
      progression in PD is needed. Using T(1rho) and T(2rho) on a 4T MRI scanner, we
      assessed the substantia nigra (SN) of nine non-demented moderately affected PD
      and ten gender- and age-matched control participants. When compared to controls,
      the SN of PD subjects had increased T(1rho) and reduced T(2rho). We also found a
      significant correlation between asymmetric motor features and asymmetry based on
      T(1rho). This study provides additional validation of T(1rho) and T(2rho) as a
      means to separate PD from control subjects, and T(1rho) may be a useful marker of
      asymmetry in PD.

PMID- 20058019
TI  - 3,4-diaminopyridine safety in clinical practice: an observational, retrospective
      cohort study.
AB  - Fatigue is one of the most common and disabling symptoms of multiple sclerosis
      (MS) and has a significant, often underestimated, impact on patients' quality of
      life. Current management is mainly symptomatic. 3,4-diaminopyridine (3,4-DAP) is
      a voltage-dependent potassium channel blocker that has been used on a named
      patient basis in Europe for many years to improve motor function and fatigue in
      patients with MS and other neuromuscular disorders, and it is undergoing the
      European approval process for Lambert-Eaton myasthenic syndrome (LEMS). The
      efficacy and safety of 3,4-DAP as symptomatic therapy in MS have not been widely
      evaluated. This study aimed to assess the safety profile of 3,4-DAP in routine
      clinical practice in an observational, retrospective study. The study involved
      669 patients of the Rennes Multiple Sclerosis Clinic, France, who were treated
      with 3,4-DAP for the relief of fatigue during the period 1998-2003. Overall,
      18.2% of patients presented adverse drug reactions (ADRs) while using moderate
      doses of 3,4-DAP (20-30 mg daily or up to 80 mg daily for patients with LEMS) for
      periods of up to 51 months. The majority of ADRs were mild to moderate and
      transient or reversible at the end of treatment (mean treatment duration = two
      months) or after dose adjustment. Most did not require discontinuation. The most
      commonly observed ADRs were paraesthesias. There was one case of epileptic
      seizure, one of hepatotoxicity and one of heart palpitations thought 'possibly'
      to be linked to 3,4-DAP. These underline the need for continued monitoring during
      treatment with 3,4-DAP.

PMID- 20058020
TI  - Seasonal variation of haemoglobin mass in internationally competitive female road
      cyclists.
AB  - In order to quantify the seasonal variability of haemoglobin mass (Hb(mass)) in
      cyclists during a competitive season, and investigate whether variability is
      associated with changes in training load or performance, Hb(mass) was measured in
      10 internationally competitive female road cyclists approximately once per month
      for 2-10 months via CO-rebreathing. Power meters were used to quantify daily load
      (Training Stress Scores) during training and racing, from which cumulative
      training load units for 7, 14, 28 and 42 day were calculated. Maximal mean power
      (MMP) for 1, 4, 10 and 25 min, performed during training or racing was used as a
      surrogate for performance. The relationship between changes in training load
      (%DeltaTraining) and changes in Hb(mass) (%DeltaHb(mass)), and between
      %DeltaHb(mass) and changes in MMP (%DeltaMMP) was established via regression
      analysis. Individual coefficients of variation (CV) in Hb(mass) ranged from 2.0
      to 4.4%. The weighted mean CV in Hb(mass) was 3.3% (90% Confidence Limits: 2.9
      3.8%) or 23 g over the average 6.6 +/- 2.3 month monitoring period. The effect of
      %DeltaTraining on %DeltaHb(mass) was small for 7 and 14 day (r = 0.22 and 0.29),
      moderate for 42 day (r = 0.35) and large for 28 day (r = 0.56). The regression
      slope was greatest for 42 day, with a 10% change in training associated with a
      approximately 1% change in Hb(mass). The relationship between %DeltaHb(mass) and
      %DeltaMMP was approximately 0.5:1 for MMP(1min),(10 min) and (25 min) and
      approximately 1:1 for MMP(4 min), respectively. Hb(mass) varies by approximately
      3% in female cyclists during a competitive season. Some of the variation may be
      related to oscillations in chronic training load.

PMID- 20058021
TI  - Effects of athletes' muscle mass on urinary markers of hydration status.
AB  - To determine if athletes' muscle mass affects the usefulness of urine specific
      gravity (U(sg)) as a hydration index. Nine rugby players and nine endurance
      runners differing in the amount of muscle mass (42 +/- 6 vs. 32 +/- 3 kg,
      respectively; P = 0.0002) were recruited. At waking during six consecutive days,
      urine was collected for U (sg) analysis, urine osmolality (U(osm)), electrolytes
      (U[Na+], U[K+] and U[Cl-]) and protein metabolites (U([Creatinine]), U([Urea])
      and U([Uric acid])) concentrations. In addition, fasting blood serum osmolality
      (S(osm)) was measured on the sixth day. As averaged during 6 days, U(sg) (1.021
      +/- 0.002 vs. 1.016 +/- 0.001), U(osm) (702 +/- 56 vs. 554 +/- 41 mOsmol kg(-1)
      H(2)O), U([Urea]) (405 +/- 36 vs. 302 +/- 23 mmol L(-1)) and U([Uric acid]) (2.7
      +/- 0.3 vs. 1.7 +/- 0.2 mmol L(-1)) were higher in rugby players than runners (P
      < 0.05). However, urine electrolyte concentrations were not different between
      groups. A higher percentage of rugby players than runners (56 vs. 11%; P = 0.03)
      could be cataloged as hypohydrated by U(sg) (i.e., >1.020) despite S (osm) being
      below 290 mOsmol kg(-1) H(2)O in all participants. A positive correlation was
      found between muscle mass and urine protein metabolites (r = 0.47; P = 0.04) and
      between urine protein metabolites and U(sg) (r = 0.92; P < 0.0001). In summary,
      U(sg) specificity to detect hypohydration was reduced in athletes with large
      muscle mass. Our data suggest that athletes with large muscle mass (i.e., rugby
      players) are prone to be incorrectly classified as hypohydrated based on U(sg).

PMID- 20058022
TI  - Clinical practice: dental trauma.
AB  - Approximately 50% of children under the age of 15 are victims of various kinds of
      injuries in the orofacial region. Post-traumatic complications may occur,
      including crown discolouration, cervical root fracture, ankylosis, root
      resorption and tooth loss. The most severe complication after dental injury in
      primary dentition can affect the developing permanent tooth germ, and various
      consequences may be seen several years later when the permanent tooth erupts. In
      the permanent dentition, the most severe dental injury affects the surrounding
      alveolar bone structure and will lead to loss of the tooth. Current literature
      emphasises that awareness of appropriate triage procedures following dental
      trauma is unsatisfactory and that delay in treatment is the single most
      influential factor affecting prognosis. What should a paediatrician know, and
      more importantly, how should he/she advise parents and caretakers? In an
      emergency situation such as tooth avulsion, reimplantation within 30 min is the
      best treatment option at the site of the accident. If reimplantation of the tooth
      is impossible, milk, saline or even saliva are the preferred transport media. The
      prognosis for an avulsed tooth depends upon prompt care, which is a determinant
      factor for successful treatment of the traumatised tooth. In all other dental
      trauma cases, it is important to refer the child to a paediatric dentist, to
      follow up the healing process and reduce late post-traumatic complications. With
      timely interventions and appropriate treatment, the prognosis for healing
      following most dental injuries is good. In conclusion, it is important that
      paediatricians are able to inform parents and caretakers about all possible and
      long-lasting consequences of different dental injuries.

PMID- 20058023
TI  - Soil shapes community structure through fire.
AB  - Recurrent wildfires constitute a major selecting force in shaping the structure
      of plant communities. At the regional scale, fire favours phenotypic and
      phylogenetic clustering in Mediterranean woody plant communities. Nevertheless,
      the incidence of fire within a fire-prone region may present strong variations at
      the local, landscape scale. This study tests the prediction that woody
      communities on acid, nutrient-poor soils should exhibit more pronounced
      phenotypic and phylogenetic clustering patterns than woody communities on fertile
      soils, as a consequence of their higher flammability and, hence, presumably
      higher propensity to recurrent fire. Results confirm the predictions and show
      that habitat filtering driven by fire may be detected even in local communities
      from an already fire-filtered regional flora. They also provide a new perspective
      from which to consider a preponderant role of fire as a key evolutionary force in
      acid, infertile Mediterranean heathlands.

PMID- 20058024
TI  - The effects of top-down versus bottom-up control on benthic coral reef community
      structure.
AB  - While climate change and associated increases in sea surface temperature and
      ocean acidification, are among the most important global stressors to coral
      reefs, overfishing and nutrient pollution are among the most significant local
      threats. Here we examined the independent and interactive effects of reduced
      grazing pressure and nutrient enrichment using settlement tiles on a coral
      dominated reef via long-term manipulative experimentation. We found that unique
      assemblages developed in each treatment combination confirming that both
      nutrients and herbivores are important drivers of reef community structure. When
      herbivores were removed, fleshy algae dominated, while crustose coralline algae
      (CCA) and coral were more abundant when herbivores were present. The effects of
      fertilization varied depending on herbivore treatment; without herbivores fleshy
      algae increased in abundance and with herbivores, CCA increased. Coral recruits
      only persisted in treatments exposed to grazers. Herbivore removal resulted in
      rapid changes in community structure while there was a lag in response to
      fertilization. Lastly, re-exposure of communities to natural herbivore
      populations caused reversals in benthic community trajectories but the effects of
      fertilization remained for at least 2 months. These results suggest that
      increasing herbivore populations on degraded reefs may be an effective strategy
      for restoring ecosystem structure and function and in reversing coral-algal phase
      shifts but that this strategy may be most effective in the absence of other
      confounding disturbances such as nutrient pollution.

PMID- 20058025
TI  - Allocation to leaf area and sapwood area affects water relations of co-occurring
      savanna and forest trees.
AB  - Water availability is a principal factor limiting the distribution of closed
      canopy forest in the seasonal tropics, suggesting that forest tree species may
      not be well adapted to cope with seasonal drought. We studied 11 congeneric
      species pairs, each containing one forest and one savanna species, to test the
      hypothesis that forest trees have a lower capacity to maintain seasonal
      homeostasis in water relations relative to savanna species. To quantify this, we
      measured sap flow, leaf water potential (Psi(L)), stomatal conductance (g (s)),
      wood density, and Huber value (sapwood area:leaf area) of the 22 study species.
      We found significant differences in the water relations of these two species
      types. Leaf area specific hydraulic conductance of the soil/root/leaf pathway (G
      (t)) was greater for savanna species than forest species. The lower G (t) of
      forest trees resulted in significantly lower Psi(L) and g (s) in the late dry
      season relative to savanna trees. The differences in G (t) can be explained by
      differences in biomass allocation of savanna and forest trees. Savanna species
      had higher Huber values relative to forest species, conferring greater transport
      capacity on a leaf area basis. Forest trees have a lower capacity to maintain
      homeostasis in Psi(L) due to greater allocation to leaf area relative to savanna
      species. Despite significant differences in water relations, relationships
      between traits such as wood density and minimum Psi(L) were indistinguishable for
      the two species groups, indicating that forest and savanna share a common axis of
      water-use strategies involving multiple traits.

PMID- 20058026
TI  - Slow decomposition of lower order roots: a key mechanism of root carbon and
      nutrient retention in the soil.
AB  - Among tree fine roots, the distal small-diameter lateral branches comprising
      first- and second-order roots lack secondary (wood) development. Therefore, these
      roots are expected to decompose more rapidly than higher order woody roots. But
      this prediction has not been tested and may not be correct. Current evidence
      suggests that lower order roots may decompose more slowly than higher order roots
      in tree species associated with ectomycorrhizal (EM) fungi because they are
      preferentially colonized by fungi and encased by a fungal sheath rich in chitin
      (a recalcitrant compound). In trees associated with arbuscular mycorrhizal (AM)
      fungi, lower order roots do not form fungal sheaths, but they may have poorer C
      quality, e.g. lower concentrations of soluble carbohydrates and higher
      concentrations of acid-insolubles than higher order roots, thus may decompose
      more slowly. In addition, litter with high concentrations of acid insolubles
      decomposes more slowly under higher N concentrations (such as lower order roots).
      Therefore, we propose that in both AM and EM trees, lower order roots decompose
      more slowly than higher order roots due to the combination of poor C quality and
      high N concentrations. To test this hypothesis, we examined decomposition of the
      first six root orders in Fraxinus mandshurica (an AM species) and Larix gmelinii
      (an EM species) using litterbag method in northeastern China. We found that lower
      order roots of both species decomposed more slowly than higher order roots, and
      this pattern appears to be associated mainly with initial C quality and N
      concentrations. Because these lower order roots have short life spans and thus
      dominate root mortality, their slow decomposition implies that a substantial
      fraction of the stable soil organic matter pool is derived from these lower order
      roots, at least in the two species we studied.

PMID- 20058027
TI  - Linking calcification by exotic snails to stream inorganic carbon cycling.
AB  - Biotic calcification is rarely considered in freshwater C budgets, despite
      calculations suggesting that calcifying animals can alter inorganic C cycling.
      Most studies that have quantified biocalcification in aquatic ecosystems have not
      directly linked CO(2) fluxes from biocalcification with whole-ecosystem rates of
      inorganic C cycling. The freshwater snail, Melanoides tuberculata, has achieved a
      high abundance and 37.4 g biomass m(-2) after invading Kelly Warm Springs in
      Grand Teton National Park. This high biomass suggests that introduced populations
      of Melanoides may alter ecosystem processes. We measured Melanoides growth rates
      and biomass to calculate the production of biomass, shell mass, and CO(2). We
      compared Melanoides biomass and inorganic C production with ecosystem C pools and
      fluxes, as well as with published rates of CO(2) production by other calcifying
      organisms. Melanoides calcification in Kelly Warm Springs produced 12.1 mmol
      CO(2) m(-2) day(-1) during summer months. We measured high rates of gross primary
      productivity and respiration in Kelly Warm Springs (-378 and 533 mmol CO(2) m(-2)
      day(-1), respectively); CO(2) produced from biocalcification increased net CO(2)
      production in Kelly Warm Springs from 155 to 167 mmol CO(2) m(-2) day(-1). This
      rate of CO(2) production via biocalcification is within the published range of
      calcification by animals. But these CO(2) fluxes are small when compared to
      ecosystem C fluxes from stream metabolism. The influence of animals is relative
      to ecosystem processes, and should always be compared with ecosystem fluxes to
      quantify the importance of a specific animal in its environment.

PMID- 20058029
TI  - Longitudinal changes of the swallowing process in subacute stroke patients with
      aspiration.
AB  - The purpose of this study was to evaluate longitudinal changes of the swallowing
      process in stroke patients with aspiration using kinematic analysis. Twenty-eight
      subacute stroke patients with aspiration on fluid at initial videofluoroscopic
      swallowing studies (VFSS) were included. Follow-up VFSS was performed at 2-4
      weeks after initial studies that were conducted at an average of 26 days after
      stroke. Temporal and spatial variables were calculated by two-dimensional motion
      analysis of hyoid bone and epiglottic movements. Swallowing process delays
      associated with hyoid bone and epiglottic movements were improved at follow-up
      studies, whereas spatial variables were not. Fourteen patients had recovered from
      aspiration at follow-up. Time to the start of the hyoid movement was longer in
      the nonrecovered patient group at initial studies (1.76 +/- 1.07 s) than in the
      recovered group (0.90 +/- 0.82 s, P=0.024). Although time-associated differences
      between the nonrecovered and recovered groups disappeared at follow-up studies,
      aspiration persisted in the nonrecovered group. This study shows that recovery
      from delays in the swallowing process is a conspicuous change during the subacute
      stage in stroke patients with aspiration. Our findings suggest that delayed
      swallowing triggering at initial VFSS is a useful predictor of poor recovery from
      aspiration in stroke patients.

PMID- 20058030
TI  - Epidemiological study of gastroenteropancreatic neuroendocrine  tumors in Japan.
AB  - BACKGROUND: There have been few epidemiological studies on gastroenteropancreatic
      neuroendocrine tumors (GEP-NETs) in Japan. METHODS: We examined the epidemiology
      of GEP-NETs [pancreatic endocrine tumors (PETs) and gastrointestinal
      neuroendocrine tumors (GI-NETs)] in Japan in 2005 using a nationwide stratified
      random sampling method. RESULTS: A total of 2,845 individuals received treatment
      for PETs. Prevalence was estimated as 2.23/100,000 with an annual onset incidence
      of 1.01/100,000. Non-functioning tumor (NF)-PET constituted 47.4%, followed by
      insulinoma (38.2%) and gastrinoma (7.9%). Distant metastases were reported in 21%
      patients with NF-PETs and occurred more frequently as tumor size increased (>2
      cm). Multiple endocrine neoplasia type 1 (MEN-1) was detected in 10% of PETs but
      only in 6.1% of NF-PETs. NF-PETs were detected incidentally by physical
      examination in 24% patients. In 2005, an estimated 4,406 patients received
      treatment for GI-NETs. Prevalence was estimated as 3.45/100,000, with an annual
      onset incidence of 2.10/100,000. The locations of GI-NETs varied: foregut, 30.4%;
      midgut, 9.6%; and hindgut, 60.0%. Distant metastases were observed in 6%. Lymph
      node metastases occurred more frequently as tumor size increased (>1 cm). The
      frequency of MEN-1 complications was 1%. Physical examination revealed GI-NETs in
      44% patients. The frequency of symptomatic GI-NETs was 3.4%. Interestingly, 77.1%
      of patients with foregut GI-NETs had type A gastritis. CONCLUSION: Our results
      show there are large differences in GEP-NETs between Japan and Western nations,
      primarily due to differences in the presence of MEN-1 in NF-PETs and the
      location, symptomatic status, and prevalence of malignancy in GI-NETs.

PMID- 20058031
TI  - Intravital imaging of DSS-induced cecal mucosal damage in GFP-transgenic mice
      using two-photon microscopy.
AB  - BACKGROUND: Two-photon laser-scanning microscopy (TPLSM) is a powerful diagnostic
      tool for real-time, high-resolution structural imaging. However, obtaining high
      quality in vivo TPLSM images of intra-abdominal organs remains technically
      challenging. MATERIALS AND METHODS: An organ-stabilizing system was applied to
      high-quality TPLSM imaging. Real-time imaging of visceral organs, such as the
      liver, spleen, kidney and intestine, of transgenic green fluorescent protein
      (GFP) mice was performed in vivo using TPLSM. The bacterial translocation model
      using dextran sodium sulfate (DSS)-induced colitis was also investigated in
      prepared GFP mice following simple surgery. This allowed the capture of
      morphological real images using in vivo TPLSM. Immunohistochemical analysis of ZO
      1 was performed to support the morphological findings of TPLSM. RESULTS AND
      CONCLUSIONS: We established an organ-stabilizing system to evaluate the real-time
      imaging of visceral organs in actin-GFP transgenic mice using in vivo TPLSM. DSS
      induced colitis showed irregularity of crypt architecture, disappearance of
      crypts, inflammatory cell infiltration and increased rolling of white blood cells
      along the vasculature. In addition, the intercellular distance of mucosal cells
      in the crypt and vascular endothelial cells in the intestinal wall was increased
      in the intestinal mucosa during DSS colitis. In DSS colitis, there was remarkable
      loss of mucosal and vascular endothelial ZO-1 expression, as could be seen by a
      decrease in ZO-1 staining. In conclusion, our observations suggested the
      possibility that our TPLSM imaging system can be used to clarify the
      pathophysiological changes in various diseases using longitudinal studies of
      microscopic changes in the same animal over long periods of time.

PMID- 20058033
TI  - Intrathecal catheterization after unintentional dural puncture during orthopedic
      surgery.
AB  - PURPOSE: We investigated whether inserting an intrathecal catheter and leaving it
      in place for 24 h after an unintentional dural puncture in orthopedic patients
      reduced the incidence of post-dural puncture headache (PDPH). METHODS: The study
      consisted of 427 patients in whom a total of 21 unintentional dural punctures had
      occurred during orthopedic surgery performed between 2002 and 2006. Seven
      patients (phase I; evaluated retrospectively) each underwent placement of an
      epidural catheter at another level after dural puncture during the period January
      2002 to February 2004. Fourteen patients (phase II; evaluated prospectively)
      received an epidural catheter through the dural tear after an unintentional dural
      puncture during the period February 2004-March 2006 RESULTS: In phase I, 5 of the
      7 patients experienced PDPH, and one required an epidural blood patch. In phase
      II, only one of the 14 patients complained of PDPH, which resolved after 48 h of
      medical therapy. No patient experienced paresthesia, neurologic or hemorrhagic
      complication, or infection. CONCLUSION: Inserting an epidural catheter through
      the dural tear following an unintentional dural puncture and leaving it in place
      for 24 h significantly reduces the incidence of PDPH.

PMID- 20058037
TI  - BuChE K variant is decreased in Alzheimer's disease  not in fronto-temporal
      dementia.
AB  - Alzheimer's disease (AD) is characterized by a significant reduction in
      AcetylCholinesterase and an increase in ButyrylCholinesterase (BuChE) activity.
      The existence of polymorphic regions on the BuChE gene has been previously
      described; the most frequently found polymorphism is the so-called K variant,
      which leads to a 30% decreased enzymatic activity. Different studies reported a
      positive association between K variant and AD, strongest among late-onset AD and
      Apolipoprotein E (APOE) e4 carriers. We analyzed APOE and BuChE polymorphisms in
      167 AD and 59 fronto-temporal dementia (FTD) patients compared with 129 healthy
      controls (HC). We reported a significantly lower frequency of the BuChE K variant
      in AD compared with HC and FTD and a significant increased frequency of the K
      variant in FTD. These results are in agreement with the known increase of the
      BuChE activity in AD and support the evidence of different molecular pathways
      involved in the pathogenesis of AD and FTD.

PMID- 20058038
TI  - Differential effects of lysophospholipids on exocytosis  in rat PC12 cells.
AB  - Secretory phospholipase A2 (sPLA2) activity is present in the CNS and the sPLA2
      IIA isoform has been shown to induce exocytosis in cultured hippocampal neurons.
      However, little is known about possible contributions of various lysophospholipid
      species to exocytosis in neuroendocrine cells. This study was therefore carried
      out to examine the effects of several lysophospholipid species on exocytosis on
      rat pheochromocytoma-12 (PC12) cells. An increase in vesicle fusion, indicating
      exocytosis, was observed in PC12 cells after external infusion of
      lysophosphatidylinositol (LPI), but not lysophosphatidylcholine or
      lysophosphatidylserine by total internal reflection microscopy. Similarly,
      external infusion of LPI induced significant increases in capacitance, or number
      of spikes detected at amperometry, indicating exocytosis. Depletion of
      cholesterol by pre-incubation of cells with methyl beta cyclodextrin and
      depletion of Ca2+ by thapsigargin and incubation in zero external Ca2+ resulted
      in attenuation of LPI induced exocytosis, indicating that exocytosis was
      dependent on the integrity of lipid rafts and intracellular Ca2+. Moreover, LPI
      induced a rise in intracellular Ca2+ suggesting that this could be the trigger
      for exocytosis. It is postulated that LPI may be an active participant in sPLA2
      mediated exocytosis in the CNS.

PMID- 20058039
TI  - A novel high molecular weight glutenin subunit from Australopyrum retrofractum.
AB  - We describe the sequence of a gene encoding a high molecular weight glutenin
      subunit (HMW-GS) expressed in the endosperm of the wheat relative Australopyrum
      retrofractum. Although the subunit has a similar primary structure to that HMW-GS
      genes present in other Triticeae species, its N-terminal domain is shorter, its
      central repetitive domain includes a unique dodecameric motif, and its C-terminal
      domain contain an extra cysteine residue. A phylogenetic analysis showed that the
      Glu-W1 gene is neither a true x- nor a true y-type subunit, although it is more
      closely related to the y-type genes present in the K and E genomes than to any
      other published HMW-GS gene. All these results indicated that this novel subunit
      may undergo a special evolutionary process different from other Triticeae
      species. A flour supplementation experiment showed that the Glu-W1 subunit has a
      negative effect on dough quality, which might be the result of interaction
      between the two closely placed cysteine residues in the C-terminal region.

PMID- 20058040
TI  - The utility of screening for perinatal depression  in the second trimester among
      Chinese: a three-wave  prospective longitudinal study.
AB  - This paper aims to study the pattern of perinatal depressive symptomatology and
      determine the predictive power of second trimester perinatal depressive symptoms
      for future perinatal periods. A population-based sample of 2,178 women completed
      the Edinburgh Postnatal Depression Scale (EPDS) in the second and third
      trimesters and at 6 weeks postpartum. Repeated measures ANOVAs were used to
      determine the EPDS scores across three stages. The predictive power of the second
      trimester EPDS score in identifying women with an elevated EPDS score in the
      third trimester and at 6 weeks postpartum were determined. The predictive power
      of the second trimester EPDS score was further assessed using stepwise logistic
      regression and receiver operator characteristic curves. EPDS scores differed
      significantly across three stages. The rates were 9.9%, 7.8%, and 8.7% for an
      EPDS score of >14 in the second and third trimesters and at 6 weeks postpartum,
      respectively. Using a cut-off of 14/15, the second trimester EPDS score
      accurately classified 89.6% of women in the third trimester and 87.2% of those at
      6 weeks postpartum with or without perinatal depressive symptomatology. Women
      with a second trimester EPDS score >14 were 11.78 times more likely in the third
      trimester and 7.15 times more likely at 6 weeks postpartum to exhibit perinatal
      depressive symptomatology after adjustment of sociodemographic variables. The
      area under the curve for perinatal depressive symptomatology was 0.85 in the
      third trimester and 0.77 at 6 weeks postpartum. To identify women at high risk
      for postpartum depression, healthcare professionals could consider screening all
      pregnant women in the second trimester so that secondary preventive intervention
      may be implemented.

PMID- 20058041
TI  - Classification issues in women's mental health:  clinical utility and etiological
      mechanisms.

PMID- 20058042
TI  - Thermodynamic and kinetic stability of a large multi-domain enzyme from the
      hyperthermophile Aeropyrum pernix.
AB  - The multi-domain enzyme isocitrate dehydrogenase from the hyperthermophile
      Aeropyrum pernix was studied by denaturant-induced unfolding. At pH 7.5, changes
      in circular dichroism ellipticity and intrinsic fluorescence showed a complex
      unfolding transition, whereas at pH 3.0, an apparently two-state and highly
      reversible unfolding occurred. Analytical ultracentrifugation revealed the
      dissociation from dimer to monomer at pH 3.0. The thermodynamic and kinetic
      stability were studied at pH 3.0 to explore the role of inter-domain interactions
      independently of inter-subunit interplay on the wild type and R211M, a mutant
      where a seven-membered inter-domain ionic network has been disrupted. The
      unfolding and folding transitions occurred at slightly different denaturant
      concentrations even after prolonged equilibration time. The difference between
      the folding and the unfolding profiles was decreased in the mutant R211M. The
      apparent Gibbs free energy decreased approximately 2 kcal/mol and the unfolding
      rate increased 4.3-fold in the mutant protein, corresponding to a decrease in
      activation free energy of unfolding of 0.86 kcal/mol. These results suggest that
      the inter-domain ionic network might be responsible for additional stabilization
      through a significant kinetic barrier in the unfolding pathway that could also
      explain the larger difference observed between the folding and unfolding
      transitions of the wild type.

PMID- 20058043
TI  - Composite mesh migration into the sigmoid colon following ventral hernia repair.
AB  - Ventral hernia repair is frequently performed with one of a number of mesh
      products, usually with good results. The current emphasis on laparoscopic repair
      has resulted in multiple composite mesh products for use in the peritoneal
      cavity. The addition of a second layer of more inert material to the mesh is
      intended to prevent adhesions with the underlying viscera, and multiple studies
      demonstrate effectiveness in doing this. Despite this, occasional complications
      may still present. We present the case of a 65-year-old man coming to our clinic
      5 years after a third ventral hernia repair/revision with composite mesh.

PMID- 20058044
TI  - Sportsmen hernia: what do we know?
AB  - Athletes and other physically active people often suffer prolonged inguinal pain,
      which can become a serious debilitating condition and may place an athlete's
      career at risk. A sportsmen hernia is a controversial cause of this chronic groin
      pain, as it is difficult to be defined. From an anatomical point of view, the
      definition and the name of this entity should be reviewed. In the majority of
      athletic manoeuvres, a tremendous amount of torque or twisting occurs in the mid
      portion of the body and the front, or anterior portion, of the pelvis accounts
      for the majority of the force. The main muscles inserting at or near the pubis
      are the rectus abdominis muscle, which combines with the transversus abdominis.
      Across from these muscles, and directly opposing their forces, is the abductor
      longus. These opposing forces cause a disruption of the muscle/tendon at their
      insertion site on the pubis, so the problem could be related to the fact that the
      forces are excessive and imbalanced, and a weak area at the groin could be
      increased due to the forces produced by the muscles. The forces produced by these
      muscles may be imbalanced and could produce a disruption of the muscle/tendon at
      their insertion site on the pubis or/and a weak area may be increased due to the
      forces produced by the muscles, and just this last possibility could be defined
      as "sportsmen hernia." In conclusion, this global entity could be considered to
      be an imbalance of the muscles (abductor and abdominal) at the pubis, that leads
      to an increase of the weakness of the posterior wall of the groin and produces a
      tendon enthesitis, once a true origin is not detected, that may lead to a
      degenerative arthropathy of the pubic symphysis in the advanced stages. Based on
      this, this entity could be re-named as "syndrome of muscle imbalance of the
      groin" and the sportsmen hernia could be considered as an entity included in this
      syndrome. It is recommended that a multidisciplinary approach is given to this
      entity, since the present literature does not supply the proper diagnostic
      studies and the correct treatment which should be performed in these patients.

PMID- 20058045
TI  - Delta/notch-like EGF-related receptor (DNER) is expressed in hair cells and
      neurons in the developing and adult mouse inner ear.
AB  - The Notch signaling pathway is known to play important roles in inner ear
      development. Previous studies have shown that the Notch1 receptor and ligands in
      the Delta and Jagged families are important for cellular differentiation and
      patterning of the organ of Corti. Delta/notch-like epidermal growth factor (EGF)
      related receptor (DNER) is a novel Notch ligand expressed in developing and adult
      CNS neurons known to promote maturation of glia through activation of Notch. Here
      we use in situ hybridization and an antibody against DNER to carry out expression
      studies of the mouse cochlea and vestibule. We find that DNER is expressed in
      spiral ganglion neuron cell bodies and peripheral processes during embryonic
      development of the cochlea and expression in these cells is maintained in adults.
      DNER becomes strongly expressed in auditory hair cells during postnatal
      maturation in the mouse cochlea and immunoreactivity for this protein is strong
      in hair cells and afferent and efferent peripheral nerve endings in the adult
      organ of Corti. In the vestibular system, we find that DNER is expressed in hair
      cells and vestibular ganglion neurons during development and in adults. To
      investigate whether DNER plays a functional role in the inner ear, perhaps
      similar to its described role in glial maturation, we examined cochleae of DNER-/
      mice using immunohistochemical markers of mature glia and supporting cells as
      well as neurons and hair cells. We found no defects in expression of markers of
      supporting cells and glia or myelin, and no abnormalities in hair cells or
      neurons, suggesting that DNER plays a redundant role with other Notch ligands in
      cochlear development.

PMID- 20058046
TI  - Impact of biologics on the prevalence of orthopedic surgery in the National
      Database of Rheumatic Diseases in Japan.
AB  - The aim of this study was to investigate changes in the treatment strategy of
      rheumatoid arthritis (RA) and the prevalence of RA-related surgeries after
      approval of biologics in Japan and to analyze the impact of biologics on the
      incidence of orthopedic surgeries using a nationwide observational cohort
      database of rheumatic diseases [National Database of Rheumatic Diseases by iR-net
      in Japan (NinJa)]. The proportion of patients using biologics linearly increased
      from 2004 (1.8%) to 2007 (10.0%), but neither the number nor type of RA-related
      surgery significantly changed during this period. Patients treated with biologics
      exhibited relatively more severe disease activity and lower physical function.
      Among patients using biologics, those who underwent RA-related surgeries
      exhibited background characteristics of longer disease duration and worse
      physical function, while disease activity was not different from patients without
      surgery. These results suggest that the potential value of biologics in avoiding
      surgical procedure is limited in patients with severe functional disorders caused
      by long disease duration. Further investigation with a longer observation period
      is required to obtain more definite conclusions as to the impact of biologics
      usage on orthopedic surgeries.

PMID- 20058047
TI  - Long-term effects of a sensitisation campaign on migraine: the Casilino study.
AB  - In 2003, we conducted a sensitisation campaign on migraine in the Casilino
      district of Rome, by sending a letter with the ID Migraine test to all the
      households and placing posters in the GPs' waiting room. Out of 195 headache
      patients recruited, 92% had migraine while 73% had never consulted a physician
      for headache. The aim of this study was to evaluate the long-term impact of this
      campaign. The follow-up was performed by a telephone interview. The questionnaire
      considered the characteristics of headache, quality of life, preventive and acute
      treatments, drug efficacy, comorbidity and subjective usefulness of the campaign.
      Of the 179 migraineurs, 90.5% (mean age 40.7 +/- 16.5, 139 females) were included
      in the follow-up. An improvement was observed in mean pain intensity (-13.9%; p <
      0.0001) and mean HIT-6 score (-6.1%; p = 0.0003). The campaign was considered to
      be useful by 63.6% of cases, while 66.1% reported an improvement in their
      clinical status. Improved patients showed a decreased mean number of days with
      headache per month (-51.7%; p < 0.0001), pain intensity (-21.8%; p < 0.0001),
      headache duration (-18.1%; p = 0.0008)and HIT-6 score (-11.7%; p < 0.0001). Our
      data suggest that the effects of a "single shot" campaign are beneficial not only
      in a short-term perspective, but even in the longterm. Moreover, the lack of
      benefit in more severe cases suggests that such patients should not be treated by
      GPs alone: patients in whom the HIT-6 score, frequency,severity or duration of
      headache worsen should be promptly referred to the headache clinic.

PMID- 20058048
TI  - Up-front temozolomide in elderly patients with glioblastoma.
AB  - Upfront temozolomide (TMZ) is often proposed for elderly patients with malignant
      gliomas as an alternative to radiotherapy (RT). A recent randomized trial showed
      that RT provides a survival benefit in elderly glioblastoma patients (>or=70
      years) with good performance status (KPS >or= 70) compared with supportive care
      alone (median survival (MS) = 29.1 vs. 16.9 weeks). We retrospectively analyzed
      all patients who were eligible for this trial, but who refused to participate and
      were finally treated with TMZ alone. Thirty-nine eligible patients (median age:
      75 years (range 70-83), median KPS: 70 (range 70-80), histologically proven
      glioblastomas) were treated up-front with oral TMZ for 1-12 cycles (mean = 5).
      One complete response and 10 partial responses were observed. Overall median
      survival (MS) was 36 weeks and median progression-free survival (PFS) was 20
      weeks for the whole group. MS was 27.4 weeks and PFS was 19.5 weeks for the 27
      patients that did not receive second-line treatment at progression. Eight grade
      III/IV toxicities (seven hematologic, one gastro-intestinal) were seen, but no
      treatment-related deaths were observed. These preliminary results support further
      randomized studies comparing TMZ with RT.

PMID- 20058049
TI  - Perfusion weighted magnetic resonance imaging to distinguish the recurrence of
      metastatic brain tumors from radiation necrosis after stereotactic radiosurgery.
AB  - After stereotactic radiosurgery (SRS) for brain metastases, delayed radiation
      effects with mass effect may occur from several months to years later, when
      tumors may also recur. Aggressive salvage treatment would be beneficial for
      patients with recurrence, but may be contraindicated for those with dominant
      radiation effect. Conventional magnetic resonance (MR) imaging does not provide
      sufficient information to differentiate delayed radiation effects from tumor
      recurrence. Positron emission tomography, MR spectroscopy, and other modalities
      sometimes may lead to false findings of tumor recurrence. We prospectively
      applied perfusion MR imaging for the management strategy after SRS because it
      gives microvascular information about the lesions. Twenty-eight lesions were
      enlarged on serial MR images in 27 patients 2-35 months (median: 11.8 months)
      after SRS for metastatic brain tumors. Each patient underwent MR perfusion
      imaging within a month after appearance of the growing enhanced lesion. To
      calculate the relative cerebral blood volume ratio (rCBV ratio), the regions of
      interest were located in the enhanced areas on the contrast-enhanced T1-weighted
      images and compared with the corresponding contralateral normal brain tissue.
      They were then followed-up with scheduled MR images with gadolinium enhancement
      at 1 to 2-month intervals afterward. Lesions which progressively increased in
      size on MR images were diagnosed as recurrences; lesions which disappeared or
      decreased in size were diagnosed as radiation necrosis. In addition, two lesions
      surgically removed were diagnosed by pathological examination. Follow-up MR
      images revealed that 21 of 28 lesions were radiation necrosis. Five lesions were
      diagnosed as recurrence on MR images, and the other two lesions were revealed as
      recurrence by pathological examination. An rCBV ratio of greater than 2.1
      provided the best sensitivity and specificity for identifying recurrent
      metastatic tumors, at 100 and 95.2%, respectively. Perfusion MR imaging provides
      useful, less invasive and in-vivo information for management of growing lesions
      after SRS, and rCBV may be a valuable index for this diagnostic purpose.

PMID- 20058050
TI  - Clinical statistics of endogenous uveitis: comparison between general eye clinic
      and university hospital.
AB  - We compared uveitis patients who attended a general eye clinic (n = 183) with
      those who attended the ophthalmology department of a university hospital (n =
      550) to examine factors that affect the clinical statistics of uveitis
      outpatients. We observed that diabetic iritis and herpetic iritis were
      significantly more frequent in the clinic whereas Vogt-Koyanagi-Harada disease
      and Behcet's disease were significantly more common in the university hospital.
      Among the so-called three leading uveitis, Behcet's disease and Vogt-Koyanagi
      Harada disease were relatively rare in the general clinic; they might be
      concentrated in the university hospital setting because these diseases require
      treatment at specialist hospitals. In addition, uveitis secondary to underlying
      diseases such as diabetic iritis and transient non-granulomatous iridocyclitis
      was generally not referred to specialist hospitals. These factors may account for
      the differences in disease frequencies observed between the two facilities.

PMID- 20058051
TI  - Orthostatic hypotension as a presenting symptom of the Guillain-Barre syndrome.
AB  - Dysautonomia is commonly observed in Guillain-Barre syndrome (GBS). However,
      hypotension is rarely a presenting and persisting symptom. A man with orthostatic
      hypotension progressively suffered with distal sensory disturbance, weakness in
      limbs, and persisting paralytic ileus. Dr Liu et al. made the diagnosis of GBS
      and successfully treated him with intravenous immunoglobulin. Chronic alcoholism
      might underlie this atypical course.

PMID- 20058052
TI  - Protein domains, catalytic activity, and subcellular distribution of mouse NTE
      related esterase.
AB  - A mammalian family of lipid hydrolases, designated "patatin-like phospholipase
      domain containing (PNPLA)" recently has attracted attention. NTE-related esterase
      (NRE) as a member of PNPLA is an insulin-regulated lysophospholipase with
      homology to neuropathy target esterase (NTE). Mouse NRE (mNRE) has a predicted
      amino-terminal transmembrane region (TM), a putative regulatory (R) domain, and a
      hydrophobic catalytic (C) domain. In the current study, we described the
      expression of green fluorescent protein (GFP)-tagged constructs of mNRE and
      mutant proteins lacking the specific protein domains. Esterase assays indicated
      that neither the TM nor R-domain was essential for mNRE esterase activity, but
      the TM significantly contributed to its activity. Subcellular distribution showed
      that mNRE was anchored in ER via its TM domain and that its C-domain was
      associated with ER. Furthermore, experiments involving proteinase treatment
      revealed that most of mNRE molecule was exposed on the cytoplasmic face of ER
      membranes. Collectively, our results for the first time revealed the protein
      domains, catalytic activity, and subcellular location of mNRE and a simplified
      model for mNRE was proposed.

PMID- 20058053
TI  - Persistent facial pain increases superoxide anion production in the spinal
      trigeminal nucleus.
AB  - Previous studies have demonstrated that there is an increase in oxidative stress
      in the cerebral cortex of rats after repeated painful stimulation and that long
      lasting pain increases the production of superoxide ion (O(2) (-)), nitric oxide
      and peroxynitrite due to the activation of AMPA and NMDA receptors. The purpose
      of the present study was to evaluate the possible role of O(2) (-) in the
      transmission of oro-facial pain. Formaldehyde 1% was injected subcutaneously into
      one vibrissal pad of adult male Sprague-Dawley rats as a model of persistent
      pain, then O(2) (-) production and superoxide dismutase (SOD) activity were
      evaluated in the left and right spinal trigeminal nuclei. O(2) (-) production was
      revealed using dihidroetidium (DHE) injected at 10 or 45 min after the formalin
      injection in conscious or anaesthetized rats. A histochemical assay for SOD was
      performed to evaluate the activity of SOD at 10 min after the formalin injection.
      The results showed a significant increase in O(2) (-) production in the
      homolateral nucleus at 45 min. However, there was no significant difference
      between the two sides at 10 min after the formalin injection. No significant
      difference was observed in SOD activity between the two sides of the spinal
      trigeminal nucleus. This study demonstrated that there is an increased production
      of O(2) (-) in the second phase but not in the first phase of the formalin test;
      thus O(2) (-) is involved in pain induced by inflammation, but not in acute pain.

PMID- 20058054
TI  - Combination of chemokine and angiogenic factor genes and mesenchymal stem cells
      could enhance angiogenesis and improve cardiac function after acute myocardial
      infarction in rats.
AB  - Gene and stem-cell therapies hold promise for the treatment of ischemic
      cardiovascular disease. Combined stem cell, chemokine, and angiogenic growth
      factor gene therapy could augment angiogenesis, and better improve heart function
      in the infarcted myocardium. In order to prove this action, we established the
      animal model of myocardial infarction (MI) was by occlusion of the left anterior
      descending artery in rats. Seven days after surgery, 5.0 x 10(6) Ad-EGFP-MSC, 5.0
      x 10(6) Ad-SDF-1-MSC, 5.0 x 10(6) Ad-VEGF-MSC, or 5.0 x 10(6) Ad-SDF-VEGF-MSC (Ad
      SDF-1-VEGF-MSC) suspension in 0.2 ml of serum-free medium was injected into four
      sites in the infarcted hearts. Results showed that MSCs transfected with Ad-VEGF
      and Ad-SDF-1 produced more SDF-1 and VEGF protein than MSCs alone, the increased
      protein levels of VEGF and SDF-1 activated Akt in MSCs transfected with Ad-VEGF
      and Ad-SDF-1, and improved the survival capability of the MSCs in vitro and in
      vivo. These transplanted cells showed that the characteristic phenotype of
      cardiomyocyte (e.g., cTnt) and endothelial cells (e.g., CD31). Four weeks after
      transplantation, reduced infarct size and fibrosis, greater vascular density, and
      a thicker left ventricle wall were observed in Ad-SDF-VEGF-MSC group. Measurement
      of hemodynamic parameters showed an improvement in left ventricular performance
      in Ad-SDF-VEGF-MSC group compared with other groups. These results demonstrated
      that combination of chemokine and angiogenic factor gene and stem cells could
      enhance angiogenesis and improves cardiac function after acute myocardial
      infarction in rats.

PMID- 20058055
TI  - Changes in E-NTPDase 3 expression and extracellular nucleotide hydrolysis during
      the myofibroblast/lipocyte differentiation.
AB  - Hepatic stellate cells (HSC) play a critical role in the development and
      maintenance of liver fibrosis. HSC are lipocytes that displayed the capacity to
      develop into myofibroblast-like cells. Ecto-nucleoside triphosphate
      diphosphohydrolases (E-NTPDases) regulate the concentration of extracellular
      nucleotides, signaling molecules that play a role in the pathogenesis of hepatic
      fibrosis. In the present study, we identified and compared the expressions of E
      NTPDase family members in two different phenotypes of the mouse hepatic stellate
      cell line (GRX) and evaluated the nucleotide hydrolysis by these cells. We show
      that both phenotypes of GRX cell line expressed NTPDase 3 and 5. However, only
      activated cells expressed NTPDase 6. In quiescent-like cells, the hydrolysis of
      triphosphonucleosides was significantly higher, and was related to an increase in
      Entpd3 mRNA expression. The diphosphonucleosides were hydrolyzed at a similar
      rate by two phenotypes of GRX cells. We suggest that up-regulation of Entpd3 mRNA
      expression modulates the extracellular concentration of nucleotides/nucleosides
      and affect P2-receptor signaling differently in quiescent-like cells and may play
      a role in the regulation of HSC functions.

PMID- 20058056
TI  - Aggregation of spectrin and PKCtheta is an early hallmark of
      fludarabine/mitoxantrone/dexamethasone-induced apoptosis in Jurkat T and HL60
      cells.
AB  - It has been shown that changes in spectrin distribution in early apoptosis
      preceded changes in membrane asymmetry and phosphatidylserine (PS) exposure.
      PKCtheta was associated with spectrin during these changes, suggesting a possible
      role of spectrin/PKCtheta aggregation in regulation of early apoptotic events.
      Here we dissect this hypothesis using Jurkat T and HL60 cell lines as model
      systems. Immunofluorescent analysis of alphaIIbetaII spectrin arrangement in
      Jurkat T and HL60 cell lines revealed the redistribution of spectrin and PKCtheta
      into a polar aggregate in early apoptosis induced by
      fludarabine/mitoxantrone/dexamethasone (FND). The appearance of an alphaIIbetaII
      spectrin fraction that was insoluble in a non-ionic detergent (1% Triton X-100)
      was observed concomitantly with spectrin aggregation. The changes were observed
      within 2 h after cell exposure to FND, and preceded PS exposure. The changes seem
      to be restricted to spectrin and not to other cytoskeletal proteins such as actin
      or vimentin. In studies of the mechanism of these changes, we found that (i)
      neither changes in apoptosis regulatory genes (e.g., Bcl-2 family proteins) nor
      changes in cytoskeleton-associated proteins were detected in gene expression
      profiling of HL60 cells after the first hour of FND treatment, (ii) caspase-3, 
      7, -8, and -10 had minor involvement in the early apoptotic rearrangement of
      spectrin/PKCtheta, and (iii) spectrin aggregation was shown to be partially
      dependent on PKCtheta activity. Our results indicate that spectrin/PKCtheta
      aggregate formation is related to an early stage in drug-induced apoptosis and
      possibly may be regulated by PKCtheta activity. These findings indicate that
      spectrin/PKCtheta aggregation could be considered as a hallmark of early
      apoptosis and presents the potential to become a useful diagnostic tool for
      monitoring efficiency of chemotherapy as early as 24 h after treatment.

PMID- 20058057
TI  - Tako-tsubo cardiomyopathy and microcirculation.
AB  - BACKGROUND: Takotsubo cardiomyopathy was described for the first time in Japan in
      the 1990s. It is very similar to the ischemic cardiopathy both for clinical and
      instrumental characteristics. His peculiarity is an alteration of the ventricular
      contraction mechanism with hypo-akinesis of the apex and lateral segments of the
      left ventricle, associated with hyper-kinesis of the heart base which is
      responsible for the typical echocardiographic aspect of a cruet during the
      systole. However, the etiology of this cardiomyopathy is still unknown despite
      the fact that numerous hypothesis have been made. A single study of 16 patients
      proved multivasal damage by a BLASH SCORE analysis of the coronary radiography.
      In our study, performed on 24 patients, we intended to assess the actual
      implication of the microcirculation by analyzing the TIMI frame count (TFC), so
      as reporting correlations between alterations of each single artery and its
      respective myocardial area. METHODS AND RESULTS: Six Cardiology Centres performed
      an International multi-centre collection of a consecutive series of 24 patients,
      of which 20 were women and four men. The average age was 67.4 years. All patients
      admitted to one of the Cardiology divisions were previously listed for symptoms
      and signs of Takotsubo cardiomyopathy. An electrocardiographic (ECG), echocardio
      gram and a hemodynamic study were carried out on each patient. The patients were
      evaluated with a follow up lasting 7 weeks. On the coronary radiography film, the
      microcirculation was examined by an analysis of the TFC according to the Gibson
      technique. The value obtained was considered pathological if it was >30 frames.
      The evaluation of the microcirculation by the TFC analysis showed that in 23 of
      the 24 patients there was a pathological slow down of the flow in the coronary
      micro- circulation. By analysing the number of involved vessels it was noted that
      nine patients had a slowdown of the general flow in all three vessels, six
      patients in only two vessels and the remaining nine in one vessel. In particular:
      in 14 patients there was an abnormal TFC in left anterior descending coronary
      artery (LAD), 16 in the right coronary artery (RCA) and 18 in the left circumflex
      coronary artery (LCX), while in one patient the picture quality in the acute
      phase did not allow an evaluation of the score in the RCA and in another patient
      in the LDA. None of the explored vessels that was responsible for the disorder of
      the microcirculation showed any stenosis. CONCLUSION: From the data evaluated by
      us, microcirculatory dysfunction seems to be present very often during acute
      phases of Takotsubo illness, but it is not the only determining factor of the
      illness.

PMID- 20058058
TI  - Body dissatisfaction among adolescent boys and girls: the effects of body mass,
      peer appearance culture and internalization of appearance ideals.
AB  - Body image dissatisfaction is a significant risk factor in the onset of eating
      pathology and depression. Therefore, understanding predictors of negative body
      image is an important focus of investigation. This research sought to examine the
      contributions of body mass, appearance conversations with friends, peer
      appearance criticism and internalization of appearance ideals to body
      dissatisfaction among adolescents. The sample was comprised of 239 (54% female)
      adolescents, with a mean age of 16 years. Self-report questionnaires were
      completed on body dissatisfaction, peer appearance conversations and criticism,
      internalization of appearance ideals, height and weight. For girls and boys, body
      mass, appearance conversations with friends, peer appearance criticism and
      internalized appearance ideals emerged as significant predictors of body
      dissatisfaction. Gender moderated the effect of body mass on body
      dissatisfaction. Internalization mediated the relationship between peer
      appearance conversations and criticism, and body dissatisfaction. These findings
      suggest that while body mass exerts a differential risk for body dissatisfaction
      among boys and girls, internalisation may represent a key psychological process
      that underpins body dissatisfaction among both boys and girls.

PMID- 20058059
TI  - A randomized controlled study of parent-assisted Children's Friendship Training
      with children having autism spectrum disorders.
AB  - This study evaluated Children's Friendship Training (CFT), a manualized parent
      assisted intervention to improve social skills among second to fifth grade
      children with autism spectrum disorders. Comparison was made with a delayed
      treatment control group (DTC). Targeted skills included conversational skills,
      peer entry skills, developing friendship networks, good sportsmanship, good host
      behavior during play dates, and handling teasing. At post-testing, the CFT group
      was superior to the DTC group on parent measures of social skill and play date
      behavior, and child measures of popularity and loneliness, At 3-month follow-up,
      parent measures showed significant improvement from baseline. Post-hoc analysis
      indicated more than 87% of children receiving CFT showed reliable change on at
      least one measure at post-test and 66.7% after 3 months follow-up.

PMID- 20058060
TI  - The genome of Beet cryptic virus 1 shows high homology to certain  cryptoviruses
      present in phylogenetically distant hosts.
AB  - This study determined the complete nucleotide sequence of Beet cryptic virus 1
      (BCV1). As expected by analogy to previously sequenced alphacryptoviruses, dsRNA1
      (2008 bp) encodes a 72.5-kDa protein containing sequence motifs characteristic
      for RNA-dependent RNA polymerases (RdRp). In addition to the full-length dsRNA1,
      a truncated form was also detected in dsRNA extracts. dsRNA2 (1783 bp) codes for
      the viral coat protein (CP) as proven by the identity of the predicted CP
      sequence to peptide sequences of the purified virion protein. The amino acid
      sequence of BCV1 RdRp as well as the 5'- and 3'-UTRs show 81-85% identity to the
      corresponding regions of Vicia cryptic virus (VCV), White clover cryptic virus 1
      (WCCV1) and Carrot cryptic virus (CaCV). The amino acid sequence identity of the
      CP is about 55-62%, moreover, a strong conservation of predicted alpha-helical
      regions was observed. The high degree of similarity of these seed- and pollen
      transmitted viruses persisting in phylogenetically distant hosts, together with
      their high similarity to fungal partitiviruses strongly supports the hypothesis
      that horizontal transfer by a fungus played a role in the emergence of the
      present cryptovirus species. The change in the distribution of cryptic viruses
      may also be due to human influence: While earlier BCV1 occurred frequently in
      sugar beet cultivars, it is very rare in cultivars currently used in agricultural
      practice and was detected in only one of the 28 cultivars investigated in our
      experiments. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s11262-009-0432-4) contains supplementary material, which is
      available to authorized users.

PMID- 20058061
TI  - Behavioral surveillance of knowledge about HIV/AIDS transmission and perceived
      need for additional knowledge in a national sample of young israeli men and women
      between 1993 and 2005.
AB  - The study examines trends in knowledge about HIV/AIDS prevention, perceived need
      for more information, and knowledge sources among 20,619 Israeli army releasees
      between 1993 and 2005. HIV/AIDS knowledge was strongly associated with education,
      lower religiosity and receiving information via the media in both genders,
      changing non-linearly over time. Need for more information was associated with
      low knowledge level among men (OR= 2.14; CI: 1.84-2.49; P < .0001) and women (OR
      1.48; CI: 1.21-1.81; P < .0001). The findings underscore the need to reach those
      groups whose knowledge remains low over time utilizing the media, the preferred
      knowledge source, recognizing that a segment believes they do not need more
      information despite having low HIV/AIDS knowledge.

PMID- 20058062
TI  - Framing male circumcision to promote its adoption in different settings.
AB  - The effectiveness of male circumcision in preventing transmission of HIV from
      females to males has been established. Those who are now advocating its
      widespread use face many challenges in convincing policy-makers and the public of
      circumcision's value. We suggest that frames are a useful lens for communicating
      public health messages that may help promote adoption of circumcision. Frames
      relate to how individuals and societies perceive and understand the world.
      Existing frames are often hard to shift, and should be borne in mind by advocates
      and program implementers as they attempt to promote male circumcision by invoking
      new frames. Frames differ across and within societies, and advocates must find
      ways of delivering resonant messages that take into account prior perceptions and
      use the most appropriate means of communicating the benefits and value of male
      circumcision to different audiences.

PMID- 20058063
TI  - AIDS denialism and public health practice.
AB  - In this paper, we respond to AIDS denialist arguments that HIV does not cause
      AIDS, that antiretroviral drugs are not useful, and that there is no evidence of
      large-scale deaths from AIDS, and discuss the key implications of the
      relationship between AIDS denialism and public health practice. We provide a
      brief history of how the cause of AIDS was investigated, of how HIV fulfills
      Koch's postulates and Sir Bradford Hil's criteria for causation, and of the
      inconsistencies in alternatives offered by denialists. We highlight clinical
      trials as the standard for assessing efficacy of drugs, rather than anecdotal
      cases or discussions of mechanism of action, and show the unanimous data
      demonstrating antiretroviral drug efficacy. We then show how statistics on
      mortality and indices such as crude death rate, life expectancy, child mortality,
      and population growth are consistent with the high mortality from AIDS, and
      expose the weakness of statistics from death notification, quoted by denialists.
      Last we emphasize that when denialism influences public health practice as in
      South Africa, the consequences are disastrous. We argue for accountability for
      the loss of hundreds of thousands of lives, the need to reform public health
      practice to include standards and accountability, and the particular need for
      honesty and peer review in situations that impact public health policy.

PMID- 20058064
TI  - Toddlers' temperament profiles: stability and relations to negative and positive
      parenting.
AB  - This study investigated the type and stability of temperament profiles in
      toddlers, and relations of profile probability to negative and positive parenting
      trajectories. Mothers (N = 96) rated their child's (41 girls and 54 boys)
      Sociability, Anger Proneness, and Activity Level four times during 1 year. The
      assessment of parenting included both maternal self-reports and observational
      measures. Latent profile analysis indicated three child temperament profiles: a
      well-adjusted 'typical' profile, an 'expressive' profile with heightened
      externalizing problems, and a 'fearful' profile with heightened internalizing
      problems. Although toddlers' profile classifications were highly stable across 1
      year, individual differences in (changes in) toddlers' temperament profile
      probability occurred. We identified negative and positive parenting as
      environmental mechanisms that were related to the development of temperament
      profiles over time. These results support the notion that, in addition to having
      a genetic base, temperament is subject to maturation and experience over time.

PMID- 20058065
TI  - Angiotensin converting enzyme inhibitors may be protective against cardiac
      complications following anthracycline chemotherapy.
AB  - Doxorubicin (DOX), despite causing cardiac toxicity, is an anthracycline
      chemotherapeutic agent that plays an important role in the treatment of breast
      cancer. Angiotensin-converting enzyme inhibitors (ACE-I) may protect against
      cardiac toxicity in patients receiving DOX chemotherapy. A total of 143 patients
      receiving DOX at the Masonic Comprehensive Cancer Clinic, University of
      Minnesota, who had two or more multigated blood pool imaging (MUGA) scans or
      echocardiograms performed between 2004 and 2007 were identified and reviewed.
      Patients with a 10% absolute drop in their ejection fraction (EF) or more to
      below 55% were identified and compared with those that did not have a 10% decline
      in EF. Impact of patient variables and the use of concurrent medications on EF
      drop were evaluated using logistic regression. Median age was 52 years old. 85
      (60%) were female. Cancer diagnosis was breast (n = 26), lymphoma (n = 92), and
      other (n = 25). In spite of a similar baseline EF in all the patients, 22/142
      (15%) patients had a significant drop in EF during DOX chemotherapy. Adjusting
      for age, the odds ratio of EF drop associated with the use of ACE-I is 0.267 (P =
      0.0940), suggesting that ACE-I has a protective effect. Cumulative DOX dose, the
      use of beta-blockers, or aspirin did not appear to be predictive or protective.
      Although not statistically significant, this study suggests that the use of ACE-I
      when given with DOX chemotherapy protects against DOX chemotherapy and warrants
      further investigation.

PMID- 20058066
TI  - Half of breast cancer patients discontinue tamoxifen and any endocrine treatment
      before the end of the recommended treatment period of 5 years: a population-based
      analysis.
AB  - Observational studies on long-term endocrine treatment among breast cancer
      patients have presented discontinuation rates on tamoxifen, but lack information
      on the continuance of any endocrine treatment [both tamoxifen and aromatase
      inhibitors (AIs)] within the same cohort. In this study we determined switching
      rates from tamoxifen to AIs, discontinuation rates of tamoxifen only,
      discontinuation rates of any endocrine treatment and determinants of first
      treatment switch and treatment discontinuation. Patients with early stage breast
      cancer (stage I-IIIa) starting on tamoxifen were selected from the linked
      Eindhoven Cancer Registry-PHARMO RLS cohort in the period 1998-2006. Continuous
      use (allowing a 60 days gap between refills) of tamoxifen only and any endocrine
      treatment were determined after various follow-up periods: 1, 2, 3, 4, and 5
      years. Time to first switch from tamoxifen to an AI was assessed. Cox regression
      was used to identify determinants of first treatment switch, discontinuation of
      tamoxifen, and discontinuation of any endocrine treatment. A total of 1,451 new
      early stage breast cancer patients started on tamoxifen. Of those, 380 had a
      treatment switch to an AI during follow-up. Of the patients followed for 5 years,
      40% continuously used tamoxifen, which was 49% for any endocrine treatment. Older
      age (older than 70 versus 50-69 years) was independently associated with
      increased discontinuation of tamoxifen and any endocrine therapy. Patients with
      two or more concomitant diseases (versus no comorbidity) showed an increased
      likelihood to stop any endocrine treatment or switch treatment from tamoxifen to
      an AI. In conclusion, up to half of the breast cancer patients starting tamoxifen
      continued 5 years of endocrine treatment. Identification of patients at risk of
      discontinuation will assist in the development of interventions to improve
      treatment continuation comparable to that of patients included in clinical
      trials.

PMID- 20058067
TI  - The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis.
AB  - It was reported that the functional polymorphism Ser326Cys in the human 8
      oxoguanine DNA glycosylase gene was associated with breast cancer risk; however,
      the published studies have inconsistent conclusions. To elucidate the effect of
      hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies
      were collected in this meta-analysis. We extracted the data from 10 case-control
      studies that were published in the PubMed database from 2003 to 2008 using the
      search phrases "human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG,
      polymorphism, genetic variation, and breast cancer." This meta-analysis included
      4,963 breast cancer cases and 4,776 control subjects. The results showed that
      individuals who carrying the hOGG1 326Cys allele in the additive model did not
      have significantly increased risk of breast cancer compared with those carrying
      the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96-1.09); similarly, no
      significant association between the hOGG1 326Cys allele and breast cancer risk
      was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI =
      0.94-1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P =
      0.78, OR = 1.01; 95% CI = 0.93-1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the
      stratified analysis, the meta-analysis showed the association between hOGG1
      326Cys allele in the additive model and breast cancer was significant in European
      subjects (P = 0.04, OR = 0.71; 95% CI = 0.51-0.98), and dominant genetic model (P
      = 0.004, OR = 0.44; 95% CI = 0.25-0.77). However, the association was not
      significant between this polymorphism and different menopausal status
      (premenopausal and postmenopausal) and the other ethnicities (Asians and
      Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a
      significant protective effect to breast cancer in European women.

PMID- 20058068
TI  - Obesity and weight change in relation to breast cancer survival.
AB  - The authors evaluated the prognostic effects of obesity and weight change after
      breast cancer diagnosis. A total of 5042 breast cancer patients aged 20-75 were
      identified through the population-based Shanghai Cancer Registry approximately 6
      months after cancer diagnosis and recruited into the study between 2002 and 2006.
      Participants were followed by in-person interviews supplemented by record linkage
      with the Shanghai Vital Statistics Registry database. Anthropometric measurements
      were taken, and information on sociodemographic, clinical, and lifestyle factors
      was collected through in-person interviews. During the median follow-up of 46
      months, 442 deaths and 534 relapses/breast cancer-specific deaths were
      documented. Women with body mass index (BMI) > or = 30 at diagnosis had higher
      mortality than women with 18.5 < or = BMI < 25; the multivariate-adjusted hazard
      ratios (HRs) were 1.55 (95% confidence interval (95% CI): 1.10-2.17) for total
      mortality and 1.44 (95% CI: 1.02-2.03) for relapse/disease-specific mortality.
      Similar results were found for pre- and post-diagnostic obesity. Women who gained
      > or = 5 kg or lost >1 kg had higher mortality than those who maintained their
      weight. No association was observed between waist-to-hip ratio and mortality. Our
      study suggests that obesity and weight change after diagnosis are inversely
      associated with breast cancer prognosis. Weight control is important among women
      with breast cancer.

PMID- 20058069
TI  - Detecting the spatial differentiation in settlement change rates during rapid
      urbanization in the Nanjing metropolitan region, China.
AB  - Urbanization produced significant landscape changes throughout the world. China
      has been experiencing accelerated urbanization during the past decades. Rapid
      land use/land over conversion occurred nationwide in urbanization, manifesting
      noteworthy characteristics of landscape dynamics. In this study, we investigated
      the spatial differentiation in settlement change rates among 1-km(2) land units
      in the Nanjing metropolitan region, a representative rapidly urbanizing region in
      China. Remotely sensed detection using Landsat TM data of 1988-2006 showed that
      settlement increase, termed as positive growth (PG), was predominant in the study
      area; while settlement decrease, termed as negative growth (NG), also had a
      considerable proportion, which was mainly attributed to the increase of green
      lands and the shrink of rural settlements. Along the urban-rural gradient, PG and
      NG showed similar mono-peaked patterns. The urban fringe zone with a consistent
      width of about 4 km was identified as the hot zone of both PG and NG over the
      three unequal periods. For both PG and NG, high-rated changes tended to exhibit
      more aggregative patterns along the gradient in the urban fringe zone. Settlement
      changes showed apparent anisotropy across directions. The directional
      distribution of PG was significantly negatively correlated to the topographic
      variables, suggesting that the mountains constrained urban expansion in an "area
      weighted inverse-distance power" form. Significant correlation between PG and NG
      in a time-lagged manner showed the "increase-decrease" fluctuation occurred in
      settlement changes, reflecting the "urban expansion-land reconfiguration" process
      in rapid urbanization in Nanjing.

PMID- 20058070
TI  - Urban and suburban aerosol in Yokohama, Japan: a comprehensive chemical
      characterization.
AB  - This article analyses elemental composition of suspended particulate matter (SPM)
      samples collected monthly from 1999 to 2005 at two locations in Yokohama, Japan.
      Microwave digestion and inductively coupled plasma mass spectroscopy was employed
      to measure Mg, Al, Ca, V, Cr, Mn, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Ag, Cd, Cs, Ba,
      Pb, and Bi. Water-soluble ions (Na(+), NH(4+), K(+), Ca(2+), Cl(-), NO(3-), and
      SO(4)2-) and carbonaceous mass (elemental and organic carbon) were detected using
      ion chromatograph and CHN analyzer, respectively. The results indicate that the
      composition of SPM on one of the sites is determined by automobile emissions and
      on the other by industrial combustions. The impact of the emission regulations
      for automobiles in large Japanese cities, which were enacted during 2002 and
      2003, on the SPM composition of the samples is also studied.

PMID- 20058071
TI  - Variations of physicochemical properties in Kalpakkam coastal waters, east coast
      of India, during southwest to northeast monsoon transition period.
AB  - A significant variation in physicochemical properties of the Kalpakkam coastal
      waters, eastern part of India, was observed during the event of southwest to
      northeast monsoon transition. Increase in nitrate, total nitrogen, and silicate
      concentrations were noticed during post-transition period. Ammonia concentration
      was at peak during transition period as compared to pre- and post-transition
      periods. Hypo-saline condition (~23 psu) was observed during post-transition as
      the surface water salinity decreased by ~10 psu from the pre-transitional values.
      Turbidity, suspended particulate matter, phosphate and total phosphorous values
      decreased marginally, coinciding with northward to southward current reversal. A
      drastic decrease (eightfold) in chlorophyll-a concentration was observed in the
      coastal water during post-transition period.

PMID- 20058072
TI  - Estimation of shipping emissions in Candarli Gulf, Turkey.
AB  - Ships are significant air pollution sources as their high powered main engines
      often use heavy fuels. The major atmospheric components emitted are nitrogen
      oxides, particulate matter (PM), sulfur oxide gases, carbon oxides, and toxic air
      pollutants. Shipping emissions cause severe impacts on health and environment.
      These effects of emissions are emerged especially in territorial waters, inland
      seas, canals, straits, bays, and port regions. Candarli Gulf is one of the major
      industrial regions on the Aegean side of Turkey. The marine environment of the
      region is affected by emissions from ships calling to ten different ports. In
      this study, NO( x ), SO(2), CO(2), hydrocarbons (HC), and PM emissions from 7,520
      ships are estimated during the year of 2007. These emissions are classified
      regarding operation modes and types of ships. Annual shipping emissions are
      estimated as 631.2 t year(-1) for NO(x), 573.6 t year(-1) for SO(2), 33,848.9 t
      year(-1) for CO(2), 32.3 t year(-1) for HC, and 57.4 t year(-1) for PM.

PMID- 20058073
TI  - First year specialist trainees' engagement with reflective practice in the e
      portfolio.
AB  - Doctors in specialist training posts in the Mersey Deanery are expected to
      reflect on their clinical practice and to document their learning experiences in
      an e-portfolio. This study aims specifically to explore how they have engaged in
      reflection on their practice and how they utilise their learning portfolio to
      document evidence of this. A modified Delphi technique was used to develop a
      grading system to identify the level of reflection recorded by participants in
      the e-portfolio. Transcripts of the reflective accounts were then analysed using
      a qualitative approach which involved coding and categorising the data. This
      study demonstrated a wide variation in both the quantity and quality of
      reflection. Of particular note in the qualitative data analysis were themes
      relating to clinical knowledge and skills, learning in practice, communication,
      feelings, types of learning experience reflected on and wider aspects of medical
      practice. Findings indicate there is variation is the extent to which doctors
      both engage in and document evidence of reflection. Further research is needed to
      explore factors that enable or inhibit the use of the e-portfolio for reflection
      and whether recorded reflection is a true picture of the cognitive process
      involved.

PMID- 20058074
TI  - Mercury in South Carolina fishes, USA.
AB  - The South Carolina Department of Health and Environmental Control has collected,
      processed, and analyzed fish tissue total mercury (Hg) since 1976. For this
      study, skin-on-filet data from 1993 to 2007 were examined to determine biotic,
      spatial and temporal trends in tissue Hg levels for SC fishes. Because of the
      relatively high number of tissue Hg values below the analytical detection limits
      interval censored regression and censored least absolute deviations were used to
      construct several models to characterize trends. Large pelagic, piscivorous fish
      species, such as bowfin (Amia calva Linnaeus 1766), had higher levels of tissue
      Hg than smaller omnivorous species. Estuarine species had relatively low levels
      of tissue Hg compared to freshwater species, while two large open ocean species,
      king mackerel (Scomberomorus cavalla Cuvier 1829) and swordfish (Xiphias gladius
      Linnaeus 1758), had higher tissue Hg readings. For a given fish species, length
      was an important predictor of tissue Hg with larger individuals having higher
      levels than smaller individuals. The USEPA Level III ecoregion and water body
      type from where the fishes were collected were important in predicting the levels
      of tissue Hg. The Middle Atlantic Coastal Plain ecoregion had fishes with the
      highest levels of tissue Hg, while the Piedmont and Southern Coastal Plain
      ecoregions had the lowest. For a given ecoregion, large reservoirs and regulated
      rivers had fish with lower levels of tissue Hg than unregulated rivers. For
      reservoirs, the size of the impoundment was a significant predictor of tissue
      mercury with small reservoirs having higher levels of tissue mercury than large
      reservoirs. Landuse and water chemistry accounted for differences seen in fish of
      various ecoregions and waterbody types. Sampling locations associated with a high
      percentage of wetland area had fish with high levels of tissue Hg. Correlation
      analysis showed a strong positive relationship between tissue Hg levels and water
      column iron, total organic carbon, ammonia, and total kjedahl nitrogen, and a
      negative relationship with alkalinity, dissolved oxygen and pH. Results from
      principle component analysis revealed patterns between waterbody type and water
      chemistry variables that suggests hydrologic modification can have profound
      effects on the levels of fish tissue Hg in riverine systems. From 1993 to 2007,
      fish tissue Hg levels have trended lower. A spike in tissue Hg levels was
      observed in 2003-2005. The drying and rewetting of the landscape after the 2002
      drought is hypothesized to have caused an increase in the methylation
      efficiencies of the system.

PMID- 20058075
TI  - Temperature dependence of the sodium pump is altered in the cerebral cortex of
      CCK2 receptor-deficient mice.
AB  - Previously we have shown that the temperature dependence of the sodium pump
      (Na(+),K(+)-ATPase) is altered under different neuropathological conditions. In
      this study we compared temperature dependence of the Na(+),K(+)-ATPase in the
      fronto-parietal cortex of CCK(2) receptor-deficient (homo- and heterozygous) and
      normal (wild-type) mice. The Arrhenius plot for Na(+),K(+)-ATPase from wild-type
      brain is non-linear with a breakpoint at 20.3 +/- 0.4 degrees C. In case of the
      brain cell membrane of CCK(2) receptor-deficient mice (homo- and heterozygous)
      the breakpoint on Arrhenius plot was detected at 26.0 +/- 1.1 degrees C and 25.4
      +/- 0.4 degrees C, respectively. The shift of the breakpoint on the Arrhenius
      plot established in CCK(2) receptor-deficiency as well as in case of some other
      pathological conditions confirms that such kind of alteration in the Na(+),K(+)
      ATPase temperature dependence is likely related to the homeostatic adjustment of
      altered function of the sodium pump.

PMID- 20058076
TI  - Improving the quality of colorectal cancer screening: assessment of familial
      risk.
AB  - BACKGROUND: Accuracy of familial risk assessment by endoscopists in determining
      colonoscopic screening and surveillance intervals is unknown. AIMS: To
      investigate follow-up recommended by endoscopists for individuals at average or
      increased familial risk, following colonoscopies that were normal or yielded
      hyperplastic polyps only. METHODS: Colonoscopy registry data was analyzed on
      5,982 patients who had colonoscopy between 2004 and 2006. Patient information was
      linked with colonoscopy procedure information and pathology results. Patients
      with a personal or family history of colorectal cancer (CRC) or polyps,
      inflammatory bowel disease, or who had diagnostic, incomplete or suboptimally
      prepped examinations were excluded. The final analysis, which included 2,414
      patients, investigated concordance of risk assessment between patient and
      endoscopist, and resulting endoscopist follow-up recommendations. RESULTS:
      Following normal colonoscopy, 76% of average risk individuals were told to follow
      up in 10 years, but if a hyperplastic polyp was found, less than 10 years was
      suggested for 76%. Many patients reporting a known familial cancer syndrome or a
      very strong family history did not have that history indicated on the
      endoscopist's procedure form, and recommended follow-up intervals were beyond
      guideline recommendations for 60.4% of the very high-risk group. CONCLUSIONS:
      Endoscopists may sometimes be unaware of the presence of familial risk factors,
      even for individuals at very high familial risk. Greater consistency and accuracy
      in familial risk assessments could significantly increase the efficacy of
      screening in preventing colorectal cancer.

PMID- 20058077
TI  - The link between psychosis and aggression in persons with dementia: a systematic
      review.
AB  - The purpose of this study was to systematically review the literature to
      determine whether aggression is linked to psychosis in persons with dementia. An
      electronic search using PubMed for articles in English focusing on psychosis and
      aggression or agitation in adults aged 65+ with dementia. Cross-sectional,
      longitudinal, and randomized controlled treatment studies examining the outcomes
      of aggression and psychosis were eligible for inclusion. Eighteen articles were
      selected for final analysis. Of the seven cross-sectional and two longitudinal
      studies directly examining the correlation of aggression and psychosis, most
      showed a positive association. Outcome data from the nine treatment studies was
      more mixed. Limited data link psychosis with aggression in persons with dementia.
      Prospectively designed studies looking at the temporal relationship of these
      variables are needed to make a stronger causal argument.

PMID- 20058078
TI  - After-care of pediatric burn victims: cultural considerations.

PMID- 20058079
TI  - Glycogen storage disease type IV: novel mutations and molecular characterization
      of a heterogeneous disorder.
AB  - Glycogen storage disease type IV (GSD IV; Andersen disease) is caused by a
      deficiency of glycogen branching enzyme (GBE), leading to excessive deposition of
      structurally abnormal, amylopectin-like glycogen in affected tissues. The
      accumulated glycogen lacks multiple branch points and thus has longer outer
      branches and poor solubility, causing irreversible tissue and organ damage.
      Although classic GSD IV presents with early onset of hepatosplenomegaly with
      progressive liver cirrhosis, GSD IV exhibits extensive clinical heterogeneity
      with respect to age at onset and variability in pattern and extent of organ and
      tissue involvement. With the advent of cloning and determination of the genomic
      structure of the human GBE gene (GBE1), molecular analysis and characterization
      of underlying disease-causing mutations is now possible. A variety of disease
      causing mutations have been identified in the GBE1 gene in GSD IV patients, many
      of whom presented with diverse clinical phenotypes. Detailed biochemical and
      genetic analyses of three unrelated patients suspected to have GSD IV are
      presented here. Two novel missense mutations (p.Met495Thr and p.Pro552Leu) and a
      novel 1-bp deletion mutation (c.1999delA) were identified. A variety of mutations
      in GBE1 have been previously reported, including missense and nonsense mutations,
      nucleotide deletions and insertions, and donor and acceptor splice-site
      mutations. Mutation analysis is useful in confirming the diagnosis of GSD IV-
      especially when higher residual GBE enzyme activity levels are seen and enzyme
      analysis is not definitive--and allows for further determination of potential
      genotype/phenotype correlations in this disease.

PMID- 20058080
TI  - Coronary CT angiography with low radiation dose.
AB  - With the introduction of 64-slice CT and dual-source CT technology, coronary CT
      angiography(CCTA) has emerged as a useful diagnostic imaging modality for the
      noninvasive assessment of coronary heart disease. Recently, the risks associated
      with ionizing radiation on CT have raised serious concerns.The main concern of
      exposure to ionizing radiation is the potential risk of cancer. CCTA involves
      much higher radiation dose with the advances in the spatial and temporal
      resolution of cardiac CT. Currently,various dose-saving algorithms, such as ECG
      (electrocardiography)-based dose modulation, reduced tube voltage, and
      prospective ECG gating, high-pitch helical scanning are available to lower
      radiation exposure during cardiac CT. Therefore, careful selection of CT scanning
      protocols is needed to keep the radiation exposure 'as low as reasonably
      achievable (ALARA)'. In this review we will discuss the radiation dose safety
      issues, the measurement of radiation dose and current use of dose-saving
      techniques in CCTA.

PMID- 20058081
TI  - The washout rate of (123)I-BMIPP and the evolution of left  ventricular function
      in patients with successfully reperfused  ST-segment elevation myocardial
      infarction: comparisons  with the echocardiography.
AB  - The evolution of the oxidative metabolism of (11)C acetate parallels the recovery
      of left ventricular(LV) contraction following acute myocardial infarction(AMI).
      This study was designed to unravel, for the first time, the impact of the global
      washout rate(WR) of (123)I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) on
      the recovery of LV function followingAMI, as evidenced from conventional
      echocardiography.Twenty consecutive patients (age: 58 +/- 13 years; 16 males and
      4 females) with ST-segment elevation myocardial infarction (STEMI) were enrolled
      and all of them underwent successful percutaneous coronary intervention (PCI).
      (123)I-BMIPP cardiac scintigraphy was performed at 7 +/- 3 days after admission.
      The WR was calculated from the polar map and the regional BMIPP defect score was
      calculated using a 17 segment model. Echocardiography was performed within 24 h
      of admission and at 3 months to record the ejection fraction (EF), the wall
      motion score index (WMSI), the ratio of the mitralinflow velocity to the early
      diastolic velocity (E/E0)and the myocardial performance index (MPI). The mean
      global WR of the BMIPP was 22.12 +/- 7.22%, and it was significantly correlated
      with the improvement of the WMSI (r = 0.61, P?0.004). However,the relative
      changes of the EF, E/E0 and MPI were not correlated with the WR. The BMIPP defect
      score (18 +/- 10) was significantly correlated with the WMSI on admission (r =
      0.74, P = 0.0002), but the defect score was not correlated with the relative
      changes of any of the echocardiographic parameters. We proved that the WR of the
      BMIPP is a promising indicator of improvement of the LV wall motion (WMSI)
      following ST-segment elevation myocardial infarction and successful reperfusion.

PMID- 20058082
TI  - Quantification in cardiac MRI: advances in image  acquisition and processing.
AB  - Cardiac magnetic resonance (CMR) imaging enables accurate and reproducible
      quantification of measurements of global and regional ventricular function, blood
      flow, perfusion at rest and stress as well as myocardial injury. Recent advances
      in MR hardware and software have resulted in significant improvements in image
      quality and a reduction in imaging time. Methods for automated and robust
      assessment of the parameters of cardiac function,blood flow and morphology are
      being developed. This article reviews the recent advances in image acquisition
      and quantitative image analysis in CMR.

PMID- 20058083
TI  - Recent developments and new perspectives on imaging of atherosclerotic plaque:
      role of anatomical, cellular and molecular MRI part III.
AB  - Atherosclerotic plaque disruption accounts for the major part of cardiovascular
      mortality and the risk of disruption appears to depend on plaque composition.
      Carotid plaques in patients, scheduled for endarterectomy, have been successfully
      characterised with MRI. MRI has the advantage of combining information about
      morphology and function. Unfortunately, the tortuosity and size of the coronary
      arteries, and the respiratory and cardiac motion hinder the in vivo
      characterisation of human coronary plaque. In addition to plaque composition
      several molecular markers of the different processes involved in atherosclerosis,
      such as integrins, matrix metalloproteinases and fibrin seem to correlate with
      risk of plaque rupture and clinical outcome. These molecular markers can be
      targeted with antibodies coupled to carriers, which are loaded with gadolinium
      for detection (molecular MRI). Several cellular/molecular MRI studies in animal
      models and some in human patients have been conducted with varying levels of
      success. The advent of clinical high field magnets, the development of contrast
      agent carriers with high relaxivity and the development of relatively new MR
      contrast techniques appear to be promising in the field of plaque imaging. Future
      MRI studies will have to focus on the molecular target of the atherosclerotic
      process, which has the highest prognostic value with regard to acute coronary
      syndromes and on the most suitable contrast agent to visualize that target.

PMID- 20058084
TI  - An implantable Teflon chip holding lithium naphthalocyanine microcrystals for
      secure, safe, and repeated measurements of pO2 in tissues.
AB  - Lithium naphthalocyanine (LiNc) is a crystalline material that has significant
      potential as a probe for EPR (electron paramagnetic resonance)-based biological
      oximetry (Pandian et al. J. Mater. Chem. 19:4138-4147, 2009a). However,
      implantation of LiNc crystals in tissues in raw or neat form is undesirable since
      dispersion of crystals in tissue may lead to loss of EPR signal, while also
      exacerbating biocompatibility concerns due to tissue exposure. To overcome these
      concerns, we have encapsulated LiNc crystals in an oxygen-permeable polymer,
      Teflon AF 2400 (TAF). Fabrication of TAF films incorporating LiNc particles
      (denoted as LiNc:TAF chip) was carried out using solvent-evaporation techniques.
      The EPR linewidth of LiNc:TAF chip was linearly dependent on oxygen-partial
      pressure (pO(2)) and did not change significantly relative to neat LiNc crystals.
      LiNc:TAF chip responded to changes in pO(2) reproducibly, enabling dynamic
      measurements of oxygenation in real time. The LiNc:TAF chips were stable in
      tissues for more than 2 months and were capable of providing repeated
      measurements of tissue oxygenation for extended periods of time. The results
      demonstrated that the newly fabricated, highly oxygen-sensitive LiNc:TAF chip
      will enhance the applicability of EPR oximetry for long-term and clinical
      applications.

PMID- 20058085
TI  - Active and biomimetic nanofilters for selective   protein separation.
AB  - Selective protein channels in cell and nuclear membranes act as gateways to
      control the passage of molecules across. The selectivity of these channels stems
      from attractive potentials of the binding sites in the transmembrane proteins.
      These channels can filter out small volume of solutions with high precision.
      Motivated from this phenomenon, we report biomimetic facilitated transport
      modality to selectively separate a target molecule from a mixture of molecules.
      The attractive potential is generated by specific antibodies immobilized inside
      15 nm diameter polycarbonate nanochannels. Two proteins with similar
      physicochemical properties (Bovine Serum Albumin 66 kDa, and Human Hemoglobin 65
      kDa) are chosen as model molecules. The protein molecules are mixed in ratios of
      1:1, 1:20 and 1:40 (Hb:BSA), and separation of molecules is demonstrated. The
      selectivity of membrane can be switched from Hb to BSA by changing the
      immobilized antibody inside the membrane channels. This approach can be used to
      selectively enrich any target molecule from a complex sample to enhance signal-to
      noise ratio for early disease diagnosis.

PMID- 20058086
TI  - Psychometric evaluation of the Impact of Cancer (IOC-CS) scale for young adult
      survivors of childhood cancer.
AB  - INTRODUCTION: Psychosocial outcomes derived from standardized and disease
      specific measures are often used in pediatric oncology; however, the reliability,
      validity and utility of these instruments in adult survivors of childhood cancer
      have yet to be established. PURPOSE: To develop and evaluate a new instrument
      that measures aspects of long-term survivorship not measured by existing tools.
      METHODS: A new candidate instrument--the Impact of Cancer for childhood cancer
      survivors (IOC-CS)--was administered to childhood cancer survivors aged 18-39 who
      were 21 years of age or younger when diagnosed with cancer. Psychometric
      properties of newly derived scales were assessed. RESULTS: Factor analyses of
      items derived eight new and specific subscales: Life Challenges, Body/Health,
      Talking With Parents, Personal Growth, Thinking/Memory Problems, Health Literacy,
      Socializing and Financial Problems. Internal consistency measurements for these
      subscales ranged from 0.70 to 0.86. Expected associations within and among the
      IOC-CS subscales and standardized measures of health-related quality of life
      (HRQOL) were observed, as were some unexpected findings. CONCLUSION: Psychometric
      analyses indicated that this initial version of the IOC-CS measures distinct and
      relevant constructs for young adult survivors of childhood cancer. Future work is
      necessary to confirm the responsiveness and further validate the instrument in
      multiple and representative samples.

PMID- 20058087
TI  - Quality of life, characteristics and survival of patients with HIV and lymphoma.
AB  - PURPOSE: We sought to compare the quality of life (QOL), characteristics, and
      survival of patients with non-Hodgkin lymphoma (NHL) with and without human
      immunodeficiency virus (HIV) infection. METHODS: Using the population-based
      cancer registry for Orange and San Diego Counties, We recruited 50 patients with
      HIV and systemic NHL (cases) and 50 age, sex and race-matched NHL patients
      without HIV (controls) diagnosed with NHL during 2002-2006. Patients completed a
      medical history survey and QOL instrument, the Functional Assessment of Human
      Immunodeficiency Virus Infection (FAHI) for cases and Functional Assessment of
      Cancer Therapy-General (FACT G) for controls. RESULTS: HIV-infected patients had
      worse overall QOL and survival than uninfected patients. QOL differences were
      more marked in the areas of functional, physical and social well-being than in
      the area of emotional well-being. HIV-infected patients had lower income and were
      less likely to have private insurance and more likely to have diffuse large B
      cell histology than uninfected patients. CONCLUSION: HIV-infected NHL patients
      had worse QOL and survival than uninfected patients, due to a combination of co
      morbidity, aggressive histology and lack of social support. However, their
      emotional well-being was comparable to that of uninfected NHL patients and better
      than historical norms for the HIV-infected.

PMID- 20058088
TI  - Quality monitoring of microbial contamination of cryopreserved parathyroid
      tissue.
AB  - Cryopreservation of parathyroid tissue (PT) provides patients undergoing
      parathyroidectomy with an option for delayed autologous heterotopic parathyroid
      transplantation. A standard protocol for quality monitoring of PT has not been
      established. This article describes a method for detecting the presence of
      bacterial contamination in PT tissue intended for autologous transplantation. PT
      was received in the tissue bank, processed under aseptic conditions, and placed
      into cryopreservation medium. Sterility testing was performed at 2 time points
      prior to cryopreservation. From January 2005 to October 2008, 47 PT samples were
      cryopreserved. The following bacteria were isolated from 11 PT specimens:
      Staphylococcus epidermidis, Staphylococcus capitis subspecies ureolyticus,
      Staphylococcus lugdunensis, Bacillus pumilus, and corynebacteria (diphtheroids).
      23% of PTs were contaminated at the time of collection, predominantly with
      indigenous bacteria. Quality monitoring using this protocol is a useful tool to
      identify tissues contaminated with bacteria.

PMID- 20058089
TI  - Twenty years of elemental analysis of marine biota within the German
      Environmental Specimen Bank--a thorough look at the data.
AB  - PURPOSE: As one component of the German ecological environment observation, the
      Environmental Specimen Bank program was initiated in the mid-1980s. Under the
      program, representative specimens of marine, fresh water, and terrestrial
      ecosystems are sampled regularly and archived under chemically stable conditions.
      An initial characterization of the samples provides data regarding the status quo
      of the respective ecosystems. The aim of the present publication is to give
      insight into these real-time monitoring data, which have been generated for the
      last 10 to 20 years. This is done exemplarily for the heavy metals cadmium (Cd),
      mercury (Hg), and lead (Pb) in marine specimens of the Baltic and the North Sea.
      METHODS: Bladder wrack (Fucus vesiculosus), blue mussel (Mytilus edulis), eelpout
      (Zoarces viviparus), and eggs of herring gulls (Larus argentatus) were sampled at
      one location in the Baltic Sea and at two sites in the North Sea (Schleswig
      Holstein Wadden Sea and Lower Saxony Wadden Sea). Annual samples were pooled,
      homogenized, and analyzed for a set of elements. Cd and Pb were quantified after
      freeze-drying and microwave digestion using inductively coupled plasma-mass
      spectrometry. Total Hg in freeze-dried samples was determined by atomic
      absorption spectrometry using a direct mercury analyzer. RESULTS: Time series
      data covering up to two decades revealed comparable cadmium levels at all three
      locations. Concentrations in bladder wrack ranged between 0.10 and 0.37 microg/g
      on a wet weight basis (ww). Respective values for blue mussel and eelpout liver
      were 0.07-0.29 and 0.01-0.10 microg/g ww. Herring gull eggs were not included in
      cadmium analyses. Declining trends were observed in North Sea bladder wrack and
      mussels, eelpout from the Lower Saxony site, and mussels from the Baltic Sea.
      Upward trends were apparent in eelpout from the Schleswig-Holstein location.
      Mercury concentrations in Baltic Sea specimens ranged from 1.1-2.7 ng/g ww in
      bladder wrack to 2.6-5.1, 26-52, and 86-226 ng/g ww in blue mussel, eelpout
      muscle, and herring gull eggs, respectively. No temporal trends were observed.
      North Sea bladder wrack had accumulated 5.4-24 ng/g ww Hg. The respective Hg
      values for blue mussel and eelpout muscle were 19-64 and 73-187 ng/g ww. Highest
      Hg contents were detected in herring gull eggs (90-1,100 ng/g ww). Declining
      trends of Hg were observed in herring gull eggs at both North Sea locations and
      in blue mussels at the Lower Saxony site. Lead concentrations in Baltic Sea
      specimens were 48-222 ng/g ww in bladder wrack, 85-189 ng/g ww in blue mussel,
      2.0-9.5 and 10-42 ng/g ww in eelpout muscle and liver, and 2.7-26 ng/g ww in
      herring gull eggs. In the North Sea, Pb concentrations were as follows: 68-397
      ng/g ww in bladder wrack, 101-507 ng/g ww in blue mussels, 2.6-35 and 5.9-158
      ng/g ww in eelpout muscle and liver, and 3.5-55 ng/g ww in herring gull eggs.
      Highest Pb-levels were found at the Lower Saxony site. Declining Pb-trends were
      observed in bladder wrack from the Baltic Sea; in bladder wrack and mussel at the
      Schleswig-Holstein location; and in bladder wrack, mussels, eelpout liver, and
      herring gull eggs at the Lower Saxony site. CONCLUSIONS: During the 10 to 20
      years of monitoring, reliable data were obtained which allow a good insight into
      metal contamination of marine biota. Assessment of the data according to OSPAR
      criteria (OSPAR 2005) revealed cadmium levels above the derived background
      concentrations in mussels of all three sites. Mercury levels above background
      concentrations were found at both North Sea locations, whereas only mussels at
      the Lower Saxony site had Pb concentrations above the reference value. Archived
      specimens are available for further analyses and questions which may arise in the
      future (speciation of elements, metallomics).

PMID- 20058090
TI  - A jump-growth model for predator-prey dynamics: derivation and application to
      marine ecosystems.
AB  - This paper investigates the dynamics of biomass in a marine ecosystem. A
      stochastic process is defined in which organisms undergo jumps in body size as
      they catch and eat smaller organisms. Using a systematic expansion of the master
      equation, we derive a deterministic equation for the macroscopic dynamics, which
      we call the deterministic jump-growth equation, and a linear Fokker-Planck
      equation for the stochastic fluctuations. The McKendrick-von Foerster equation,
      used in previous studies, is shown to be a first-order approximation, appropriate
      in equilibrium systems where predators are much larger than their prey. The model
      has a power-law steady state consistent with the approximate constancy of mass
      density in logarithmic intervals of body mass often observed in marine
      ecosystems. The behaviours of the stochastic process, the deterministic jump
      growth equation, and the McKendrick-von Foerster equation are compared using
      numerical methods. The numerical analysis shows two classes of attractors: steady
      states and travelling waves.

PMID- 20058091
TI  - Cardiac and pericardial abnormalities on chest computed tomography: what can we
      see?
AB  - Radiological reporting in chest computed tomography (CT) is primarily focused on
      assessing pulmonary and mediastinal abnormalities, thereby tending to overlook
      the heart. However, incidental cardiac abnormalities are often encountered and
      misdiagnosed, which may potentially impact the patient's treatment or necessitate
      further investigation. The aim of this pictorial review is to provide a stepwise
      approach to assessing the heart on routine non-electrocardiographic-gated (non
      ECG-gated) chest CT and describing common and less frequent cardiac
      abnormalities.

PMID- 20058092
TI  - Temporal trend of diagnostic medical exposure to the Emilia-Romagna region
      population.
AB  - PURPOSE: This paper illustrates the annual trends in medical radiation exposure
      due to conventional radiography (CR), computed tomography (CT) and nuclear
      medicine (NM) procedures of the Emilia-Romagna population from 2001 to 2006.
      MATERIALS AND METHODS: We gathered information about the type, number and mean
      doses of CR, CT, and NM examinations performed in 17 hospitals of the Emilia
      Romagna region. In particular, numerical values of the following dosimetric
      parameters were requested: entrance skin dose for CR, CT dose index and dose
      length product for CT and activity administered for NM. Lastly, the annual
      collective dose S and annual average per-caput dose were calculated. RESULTS: The
      13 diagnostic imaging procedures that were the greatest contributors to the
      Emilia-Romagna population dose between 2001 and 2006 were identified and, for the
      year 2006, their percentage contribution to total procedures and population dose
      are indicated. CR, CT and NM accounted for 12%, 78% and 10% of the dose, and 83%,
      15% and 2% of total procedures, respectively. The annual trends of S and average
      per capita dose are shown, and the theory underlying the use of these parameters
      is briefly discussed. CONCLUSIONS: This type of study relies heavily on the
      analysis of field data and as such, the growing attention paid in recent years to
      procedure optimisation should continue, and expand even for the justification of
      the procedures themselves as justification has a significant impact on the
      reduction of S and per-caput doses.

PMID- 20058093
TI  - Dose reduction in spiral CT coronary angiography with dual source  equipment.
      Part II. Dose surplus due to slope-up and slope-down of  prospective tube current
      modulation in a phantom model.
AB  - PURPOSE: This study was undertaken to estimate surplus radiation dose in
      retrospectively electrocardiography (ECG)-gated dual-source computed tomography
      coronary angiography (DSCT-CA) due to the slope-up and slope-down of the tube
      current using prospectively ECG-triggered tube modulation. MATERIALS AND METHODS:
      We used an anthropomorphic phantom with an ECG-gated retrospective protocol and a
      DSCT scanner (Definition, Siemens). We used four tube current modulation
      algorithms: narrow pulsing window, with tube current reduction to 20% (A) and 4%
      (B) of peak current; and wide pulsing window, with tube current reduction to 20%
      (C) and 4% (D). Each algorithm was applied at five heart rates (HR=45, 60, 75, 90
      and 120 bpm) with adaptive pitch values (0.2-0.5). Data sets were reconstructed
      in 5% increments from 0-95% of the R-R interval. Noise was measured at each R-R
      step in order to identify low noise (100% dose), medium noise (slope-up/down) and
      high noise (4/20% dose). Width of the transition window (slope-up/slope-down from
      4/20% to 100% dose) was calculated. The surplus dose due to slope-up/slope-down
      was calculated. RESULTS: Surplus dose was 19% (A), 34% (B), 14% (C) and 21% (D).
      The transition window lasted 10%+10% (slope-up + down) for HR <75 bpm and all HR
      in C (except for 120 bpm; 25%+15%), 15%+15% for HR >90 bpm (A). For C and D,
      instead, the slope-up increased with progressively higher HR (10%-25% of the R-R
      interval, except for 90 bpm, 10%), whereas the slope-down remained constant at 5%
      (except for 120 bpm; 10%). CONCLUSIONS: The adaptive ECG-pulsing windows produced
      an increment of the surplus dose with increasing HR. The transition window was a
      constant source of surplus radiation dose in the range of 14%-34%.

PMID- 20058094
TI  - Transverse dural sinuses: incidence of anatomical variants and flow artefacts
      with 2D time-of-flight MR venography at 1 Tesla.
AB  - PURPOSE: This study sought to identify imaging criteria useful in discriminating
      anatomical variants from thrombosis of the posterior intracranial venous system.
      MATERIALS AND METHODS: A total of 102 patients underwent coronal unenhanced two
      dimensional time-of-flight (2D ToF) magnetic resonance (MR) venography.
      Transverse sinus (TS) calibre and asymmetry were considered. Oval (O-FG) and
      linear (L-FG) flow gaps were recorded. Several slices of the 2D ToF sequence were
      applied perpendicularly to the TS within each FG to avoid in-plane saturation.
      RESULTS: Mean calibre of the right TS was significantly greater than the
      contralateral sinus (6.5 mm+/-1.84 vs 5.1 mm+/-1.72). Right and left dominance
      was observed in 61% and 17% of cases, respectively. The mean right-left TS
      diameter was 5.77 mm. Among 204 TS, 44 L-FG and 42 O-FG were observed. Partial L
      FG (<2/3 of TS) never involved the distal TS. No L-FG was observed in a dominant
      TS. Supplementary sagittal 2D ToF images disclosed blood flow in all but two L
      FGs. O-FGs were mostly observed laterally (91%). CONCLUSIONS: L-FGs in a dominant
      TS, partial L-FGs in the distal part or O-FG in the medial part of any TS, a left
      right mean diameter <3 mm and absence of flow even in ToF images perpendicular to
      the direction of blood flow should raise the suspicion of sinus pathology.

PMID- 20058095
TI  - Pulmonary congenital cystic disease in adults. Spiral computed tomography
      findings with pathologic correlation and management.
AB  - PURPOSE: The aim of this study was to assess the computed tomography (CT)
      features of intrapulmonary congenital cystic diseases in adults and to correlate
      the imaging features with the pathological findings, with emphasis on the
      oncogenic potential of the lesions. MATERIALS AND METHODS: We retrospectively
      reviewed the CT scans in three institutions from August 1996 to December 2008, of
      nine patients (six men, three women; mean age 48.6 years; range 26-75 years) who
      had histological diagnosis of pulmonary cystic disease after surgery. Six
      patients had a diagnosis of intrapulmonary bronchogenic cyst (IBC), and three had
      a type-I cystic adenomatoid malformation (CAM). In one case, intralobar
      sequestration (ILS) was associated with type-I CAM. RESULTS: Three patients were
      symptomatic and six were asymptomatic. On CT scans, IBCs showed homogeneous fluid
      attenuation (n=2), air-fluid level (n=2), air attenuation (n=1) or soft-tissue
      attenuation (n=1). The surrounding lung tissue showed areas of band-like linear
      attenuation in three IBCs, atelectasia in two and mucocele-like areas in one. On
      CT, type-I CAM appeared as a unilocular cystic lesion with air-fluid level (n=1)
      or air content (n=1). Both cases had thin walls surrounded by normal lung
      parenchyma. ILS appeared as a fluid-filled cyst with afferent and efferent
      vessels. Of the six IBCs, one occurred in the upper right lobe, two in the middle
      lobe and three in the lower right lobe. Of the three type-I CAMs, one was in the
      upper left lobe and one in the middle lobe. The type-I CAM associated with ILS
      was located in the left lower lobe. CONCLUSIONS: The similar CT patterns preclude
      differentiation between IBC and type-I CAM. Surgical resection of all
      intrapulmonary cystic lesions detected in adults is mandatory because type-I CAM
      is a precursor of mucinous bronchioloalveolar carcinoma.

PMID- 20058096
TI  - Sacral nerve stimulation induces changes in the pelvic floor and rectum that
      improve continence and quality of life.
AB  - PURPOSE: Sacral nerve stimulation (SNS) can improve fecal incontinence, though
      the exact mechanism is not known. This study examines the following hypotheses:
      SNS leads to contraction of the pelvic floor, influences rectal perception, and
      improves continence and quality of life. METHODS: Fourteen patients with sacral
      nerve stimulators implanted for fecal incontinence were examined prospectively.
      Morphological and functional assessment was done by endosonography, manometry,
      and volumetry with the stimulator turned on and off in direct succession.
      Questionnaires were used to determine incontinence and quality of life. RESULTS:
      With the stimulator turned on, rectal filling conditions were perceived only at
      higher volumes; in particular, the defecation urge was sensed only at higher
      volumes. There was also a reduction in the diameters of the external and internal
      anal sphincters and a decrease in the distance between the anal mucosa and the
      symphysis as a sign of pelvic floor elevation. Six months after surgery,
      continence and quality of life were markedly better than before the operation.
      CONCLUSIONS: We were able to confirm the hypotheses given above. The improvements
      of pelvic floor contraction and rectal perception are rapid adjustment processes
      in response to stimulation of sacral nerves S3/S4 when turning on the stimulator.

PMID- 20058097
TI  - Can a short course of prophylactic low-dose proton pump inhibitor therapy prevent
      stomal ulceration after laparoscopic Roux-en-Y gastric bypass?
AB  - BACKGROUND: The purpose of this retrospective analysis was to determine if a
      short course of prophylactic proton pump inhibitor (PPI) therapy can prevent
      stomal ulceration after laparoscopic Roux-en-Y gastric bypass (LRYGBP). METHODS:
      Four hundred forty-nine consecutive patients who underwent LRYGBP and had a
      minimum of 6 months follow-up were included. Patients were categorized in two
      groups: patients with Helicobacter pylori at preoperative endoscopy (HP group)
      and patients without H. pylori (non-HP group). All patients in the HP group were
      medically treated prior to surgery. In both groups, almost half of the patients
      received low-dose proton pump inhibitors (omeprazole 20 mg daily) for 1 month
      following LRYGBP. RESULTS: The incidence of stomal ulceration in the HP group was
      not statistically different from the incidence in the non-HP group (7/86, 8.14%
      vs. 41/363, 11.29%; p = 0.559). When comparing the patients who did receive PPI
      therapy with the patients who did not receive PPI therapy within the non-HP
      group, there was no significant reduction in development of stomal ulceration
      (18/169, 10.65% vs. 23/194, 11.86%; p = 0.743). When comparing the patients who
      did receive PPI therapy with the patients who did not receive PPI therapy within
      the HP group, there is a significant reduction in development of stomal
      ulceration (0/41, 0% vs. 7/45, 15.56%; p = 0.0123). CONCLUSION: Development of
      stomal ulceration in patients tested positive for H. pylori prior to LRYGBP can
      be prevented by prophylactic low-dose PPI therapy following surgery.

PMID- 20058098
TI  - Does initial point of care influence neuro-ICU outcomes?

PMID- 20058099
TI  - A double pituitary adenoma presenting as a prolactin-secreting tumor with partial
      response to medical therapy. Case report.
AB  - Double pituitary adenomas are difficult to recognize pre-operatively as only a
      single mass may be appreciated on imaging. We present herein a giant prolactin
      secreting pituitary adenoma in a middle-aged man that had responded partially to
      dopamine agonist therapy. The excised specimen demonstrated a double adenoma. The
      prolactin-producing one displayed the expected morphological changes resulting
      from medical therapy, while the other, a gonadotroph adenoma, did not. The
      failure of tumor shrinkage can be attributed to the presence of a double adenoma,
      a previously unreported cause of failure of medical therapy in prolactinoma.

PMID- 20058100
TI  - A case of signet ring carcinoma of the appendix: dilemmas in differential
      diagnosis and management.
AB  - PURPOSE: Signet ring carcinoma (SRC) of the appendix consists one of the most
      biologically virulent cancers. We present the case of a patient with primary SRC
      complicated by the development of acute inflammation of the appendix. CASE
      REPORT: A 78-year-old man was admitted due to a 5-day history of increasing
      colicky abdominal pain and vomiting. Clinical examination revealed a firm, tender
      mass in the right ileac fossa. Laparotomy confirmed a tumor mass which appeared
      to originate from the appendix. The affected part of the bowel was resected and a
      right hemicolectomy with an end-to-side ileotransverse anastomosis was performed.
      The appendix was notably thickened with an ulcerated wall containing sinus
      tracts, chronic inflammation, and scarring. Moreover, a focus of SRC was
      detected. CONCLUSIONS: Appendiceal SRC is a rare entity, which may sometimes be
      confused with other pathologies providing difficulties in differential diagnosis,
      having an impact on therapeutic decisions and affecting prognosis.

PMID- 20058101
TI  - Well-differentiated mesenteric liposarcoma with osseous metaplasia: a potential
      diagnostic dilemma for the pathologist.
AB  - BACKGROUND: Mesenteric liposarcoma is a rare intra-abdominal sarcoma with very
      few cases reported in the available English literature. Incomplete resection of
      the tumor leads to recurrence, and recurrent tumors carry a risk of
      dedifferentiation. Dedifferentiation in liposarcoma manifests as a nonlipogenic
      sarcoma, which is usually high-grade and may show osteosarcomatous
      differentiation rarely. To the best of our knowledge, osteoid metaplasia in a
      well-differentiated liposarcoma without evidence of dedifferentiation has not
      been documented in the available literature. CASE: We describe the case of a
      middle-aged adult man with a well-differentiated liposarcoma of the mesentery.
      The patient presented with a recurrent tumor 5 years after the initial surgery.
      At recurrence, the histological features were those of a well-differentiated
      liposarcoma with focal osseous metaplasia without any evidence of
      dedifferentiation in the extensive sections examined. CONCLUSION: Osseous
      metaplasia is a rare phenomenon in lipomas and dedifferentiated liposarcomas.
      Such an occurrence in a recurrent well-differentiated liposarcoma is a perplexing
      problem due to the potential confusion with dedifferentiation. This needs to be
      recognized to avoid overzealous chemotherapy and/or radiotherapy, which is
      required for dedifferentiated tumors.

PMID- 20058102
TI  - Gene-modified stem cells combined with rapid prototyping techniques: a novel
      strategy for periodontal regeneration.
AB  - Periodontal disease, a worldwide prevalent chronic disease in adults, is
      characterized by the destruction of the periodontal supporting tissue including
      the cementum, periodontal ligament and alveolar bone. The regeneration of damaged
      periodontal tissue is the main goal of periodontal treatment. Because
      conventional periodontal treatments remain insufficient to attain complete and
      reliable periodontal regeneration, periodontal tissue engineering has emerged as
      a prospective alternative method for improving the regenerative capacity of
      periodontal tissue. However, the potential of periodontal regeneration seems to
      be limited by the understanding of the cellular and molecular events in the
      formation of periodontal tissue and by the insufficient collaboration of multi
      disciplinary research that periodontal tissue engineering involves. In this
      paper, we first reviewed the recent advancements in stem cells, signaling
      factors, and scaffolds that relate to periodontal regeneration. Then we speculate
      that specific genes would improve regenerative capacity of these stem cells,
      which could differentiate into cementoblasts, osteoblasts and fibroblasts. In
      addition, the 3D scaffolds that mimic the different structure and physiologic
      functions of natural fibro-osseous tissue could be fabricated by rapid
      prototyping (RP) techniques. It was therefore hypothesized that gene-modified
      stem cells combined with rapid prototyping techniques would be a new strategy to
      promote more effective and efficient periodontal regeneration.

PMID- 20058103
TI  - Design and performance from an integrated PET/MRI system  for small animals.
AB  - OBJECTIVE: Although simultaneous measurements of PET and magnetic resonance
      imaging (MRI) can provide interesting results in molecular imaging research, most
      of the combined systems are huge and animal handling in the system is not easy.
      To minimize these problems, we developed a compact integrated PET/MRI (iPET/MRI)
      system for small animals. METHODS: For the iPET/MRI system, a new MR-compatible
      PET and a permanent magnet open MRI were designed. In the MRI, a tunnel is opened
      at the yoke of the magnet. The position-sensitive photo-multiplier tubes (PSPMTs)
      of the MR-compatible PET are positioned at the back of the yoke where the
      magnetic field is sufficiently low. The scintillators for the PET system are
      positioned at the center of the MRI magnets, and the direction of the
      scintillation photons is changed by slanted light guides, and they are fed to the
      PSPMTs by 75 cm long optical fiber bundles. The PET detectors employed two types
      of LGSO crystals (1.9 mm x 2.2 mm x 6 mm and 7 mm) with different decay times (33
      and 43 ns) for depth of interaction detection. Sixteen optical fiber-based block
      detectors are arranged in a 112 mm diameter ring. RESULTS: The transaxial field
      of-view (FOV) of the PET system is ~80 mm, and the axial FOV is 21 mm which can
      be enlarged by the axial motion of the PET detector ring during MRI acquisition.
      The transaxial and axial resolutions at the center of the PET system was 2.9 and
      2.4 mm FWHM, respectively. The absolute sensitivity was 1.5% at the center of the
      axial FOV. Phantom images revealed no artifact in either the PET or MRI images.
      We successfully obtained simultaneously measured small animal images using the
      iPET/MRI system. CONCLUSION: The open geometry of the developed iPET/ MRI
      facilitates easy accessibility to the subject. The iPET/ MRI system appears to be
      a promising tool for molecular imaging research.

PMID- 20058104
TI  - The effect of giving detailed information about intravenous  radiopharmaceutical
      administration on the anxiety level  of patients who request more information.
AB  - OBJECTIVES: Nuclear medicine procedures use radiopharmaceuticals, which produce
      radiation and potential adverse reactions, albeit at a low rate. It is the
      patient's ethical, legal, and medical right to be informed of the potential side
      effects of procedures applied to them. Our purpose was to determine the effect of
      providing information about intravenous radiopharmaceutical administration on the
      anxiety level of patients who request more information. MATERIALS AND METHODS:
      This study was completed in two separate Nuclear Medicine Departments. The study
      included 620 (247 M, 373 F) patients who had been referred for myocardial
      perfusion, bone, dynamic renal, and thyroid scintigraphic examinations. The
      patients were divided into two groups according to whether they requested more
      information or not. Group 1 consisted of 388 patients who wanted to receive more
      information about the procedure, while Group 2 consisted of 232 patients who did
      not request additional information. The State-Trait Anxiety Inventory (STAI-S and
      STAI-T) was used to determine a patient's anxiety level. After simple information
      was given, state and trait anxiety levels were measured in both groups. We gave
      detailed information to the patients in Group 1 and then measured state anxiety
      again. Detailed information included an explanation of the radiopharmaceutical
      risk and probable side effects due to the scan procedure. RESULTS: There was no
      statistical difference between Groups 1 and 2 in STAI-T or STAI-S scores after
      simple information was given (p = 0.741 and p = 0.945, respectively). The mean
      value of STAI-S score was increased after the provision of detailed information
      and there was a statistically significant difference between after simple
      information SATI-S and after detailed information STAI-S (p < 0.001). The STAI-S
      score was increased in 246 patients and decreased in 110 patients after detailed
      information, while there was no change in 32 patients. After detailed
      information, the greatest increase in STAI-S score was seen in the myocardial
      perfusion scan patients, when evaluating according to scan procedure (p < 0.001).
      However, in the dynamic renal patient group, there was no statistical difference
      (p = 0.271). CONCLUSIONS: Informed consent including detailed information about
      radiation exposure, the risk factors, and potential adverse reactions of
      intravenous radiopharmaceutical administration increased the patients' anxiety
      level in those who request more information.

PMID- 20058105
TI  - Additional value of integrated PET/CT over PET alone  in the initial staging and
      follow up of head and neck malignancy.
AB  - OBJECTIVE: Clinical application of FDG-PET in head and neck cancer includes
      identification of metastases, unknown primary head and neck malignancy, or second
      primary carcinoma, and also recurrent tumor after treatment. In this study, the
      additional value of PET/CT fusion images over PET images alone was evaluated in
      patients with initial staging and follow up of head and neck malignancy. METHODS:
      Forty patients with suspected primary head and neck malignancy and 129 patients
      with suspected relapse after treatment of head and neck malignancy were included.
      FDG-PET/CT study was performed after the intravenous administration of FDG (5
      MBq/kg). Target of evaluation was set at primary tumor, cervical lymph node, and
      whole body. PET images and PET with CT fusion images were compared. Sensitivity,
      specificity, accuracy, positive predictive value (PPV), and negative predictive
      value (NPV) were calculated. Results of PET and PET/CT were compared with
      postoperative histopathological examination, and case by case comparison of PET
      and PET/CT results for each region was performed. The additional value of CT
      images over PET only images was assessed. Statistical differences in sensitivity
      and specificity were evaluated. RESULTS: In the comparative evaluation of 507
      targets by PET alone and PET/CT, 401 targets showed agreement of the results. Of
      the 106 discordant targets, 103 showed a positive result on PET alone and
      negative result on PET/CT. These results showed a significant difference (p<
      0.01). Sensitivity of PET/CT was slightly higher than that of PET without
      statistical significance, while specificity of PET/CT was significantly higher
      than that of PET alone (Initial staging: 90.5% vs. 62.2%, p < 0.01; Follow up:
      97.2% vs. 74.4%, p < 0.01). In Fisher's direct probability test, a significant
      difference was noted in the sensitivity (Initial staging: 91.3% vs. 87.0%, p <
      0.01; Follow up: 93.9% vs. 91.4%, p <0.01). CONCLUSIONS: Combined PET/CT showed
      improved diagnostic performance than PET alone by decreasing the number of false
      positive findings in patients with initial staging and follow up of head and neck
      malignancy.

PMID- 20058106
TI  - In vitro and in vivo evaluation of proniosomes containing celecoxib for oral
      administration.
AB  - The objectives of this research were to prepare celecoxib proniosomes and
      evaluate the influence of proniosomal formulation on the oral bioavailability of
      the drug in human volunteers. A new proniosomal delivery system for a poorly
      water-soluble drug such as celecoxib was developed and subjected to in vitro and
      in vivo studies. Proniosomes were prepared by sequential spraying method, which
      consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1:
      0.1, respectively. The average entrapment percent of celecoxib proniosome-derived
      niosomes was about 95%. The prepared proniosomes showed marked enhancement in the
      dissolution of celecoxib as compared to pure drug powder. The bioavailability of
      200 mg single dose of both celecoxib proniosomal formulation and a conventional
      marketed celecoxib capsule was studied in human volunteers. The obtained results
      show that the proniosomal formulation significantly improved the extent of
      celecoxib absorption than conventional capsule. The mean relative bioavailability
      of the proniosomal formulation to the conventional capsule was 172.06 +/- 0.14%.
      The mean T (max) for celecoxib was prolonged when given as proniosomal capsule.
      There was no significant difference between the values of K (el) and t (1/2) for
      both celecoxib preparations. In conclusion, the proniosomal oral delivery system
      of celecoxib with improved bioavailability was established.

PMID- 20058107
TI  - Determination of end point of primary drying in freeze-drying process control.
AB  - Freeze-drying is a relatively expensive process requiring long processing time,
      and hence one of the key objectives during freeze-drying process development is
      to minimize the primary drying time, which is the longest of the three steps in
      freeze-drying. However, increasing the shelf temperature into secondary drying
      before all of the ice is removed from the product will likely cause collapse or
      eutectic melt. Thus, from product quality as well as process economics
      standpoint, it is very critical to detect the end of primary drying. Experiments
      were conducted with 5% mannitol and 5% sucrose as model systems. The apparent end
      point of primary drying was determined by comparative pressure measurement (i.e.,
      Pirani vs. MKS Baratron), dew point, Lyotrack (gas plasma spectroscopy), water
      concentration from tunable diode laser absorption spectroscopy, condenser
      pressure, pressure rise test (manometric temperature measurement or variations of
      this method), and product thermocouples. Vials were pulled out from the drying
      chamber using a sample thief during late primary and early secondary drying to
      determine percent residual moisture either gravimetrically or by Karl Fischer,
      and the cake structure was determined visually for melt-back, collapse, and
      retention of cake structure at the apparent end point of primary drying (i.e.,
      onset, midpoint, and offset). By far, the Pirani is the best choice of the
      methods tested for evaluation of the end point of primary drying. Also, it is a
      batch technique, which is cheap, steam sterilizable, and easy to install without
      requiring any modification to the existing dryer.

PMID- 20058108
TI  - Chitosan-mediated siRNA delivery in vitro: effect of polymer molecular weight,
      concentration and salt forms.
AB  - The aim of this study was to investigate chitosan/siRNA complexes formulated with
      various chitosan salts (CS) including chitosan aspartate (CS-Asp), chitosan
      glutamate (CS-Glu), chitosan acetate (CS-Ac), and chitosan hydrochloride (CS-HCl)
      for in vitro siRNA delivery into stable and constitutive enhanced green
      fluorescent protein (EGFP)-expressing HeLa cells. The CS/siRNA complexes were
      characterized by 2% agarose gel electrophoresis and investigated for their
      transfection efficiency in stable and constitutive EGFP-expressing HeLa cells.
      The cytotoxicity of the complexes was determined by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The formation of complexes
      CS/siRNA is mainly dependent on the weight ratio, whereas salt form and molecular
      weight has less effect. The particle sizes of the complete complexes were in the
      range of 270-373 nm except the complete complex of CS-Ac, with a slightly
      positive charge of less than 2 mV. The ability of CS to transfer functionally
      active siRNA into cell culture is mainly dependent on the weight ratio and
      molecular weight of CS whereas salt form of CS has less effect. The high gene
      silencing efficiency was observed with low MW of CS (20 kDa) and high weight
      ratio of 32. Over 80% average cell viabilities were observed for CS/siRNA
      complexes in all weight ratios comparison to untreated cells. This study suggests
      CS salts have the potential to be used as safe siRNA delivery vectors.

PMID- 20058109
TI  - Natural course of asymptomatic deep venous thrombosis in hip surgery without
      pharmacologic thromboprophylaxis in an Asian population.
AB  - BACKGROUND: The clinical importance of asymptomatic deep venous thrombosis in
      elective hip surgery is not clearly known. QUESTIONS/PURPOSES: We determined the
      preoperative and postoperative incidences of asymptomatic deep venous thrombosis,
      identified preoperative factors associated with postoperative deep venous
      thrombosis or pulmonary embolism, and established its natural course in patients
      who underwent elective hip surgery without receiving pharmacologic
      thromboprophylaxis. PATIENTS AND METHODS: We reviewed 184 patients who underwent
      consecutive elective hip surgeries with a mechanical thromboprophylaxis regimen
      including combined general and epidural anesthesia, intraoperative calf
      bandaging, early mobilization, and postoperative intermittent pneumatic
      compression with additional use of elastic stockings. Duplex ultrasonography was
      performed routinely to diagnose deep venous thrombosis in all patients before
      surgery and on Postoperative Days 3 and 21. All patients with postoperative deep
      venous thrombosis underwent additional ultrasonography at 3-month intervals, and
      all patients were followed postoperatively for 6 months or more. RESULTS:
      Preoperatively, we found asymptomatic deep venous thrombosis in two patients
      (1%); both thromboses had completely and spontaneously resolved by Postoperative
      Day 21. Postoperatively, no patients had a fatal or symptomatic pulmonary
      embolism or proximal deep venous thrombosis, but nine patients (5%) had
      asymptomatic distal deep venous thrombosis develop, with no preoperative
      associated factors. These nine patients were followed closely without
      anticoagulant drugs, and all thromboses had disappeared without pulmonary
      embolism or thrombophlebitis by 6 months. CONCLUSIONS: The incidence of
      preoperative and postoperative deep venous thrombosis was low in an Asian
      population having elective hip surgery and a nonpharmacologic thromboprophylaxis
      regimen. There were no preoperative factors associated with postoperative deep
      venous thrombosis, and all asymptomatic deep venous thromboses resolved
      spontaneously without associated pulmonary embolism or thrombophlebitis. LEVEL OF
      EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 20058110
TI  - Subchondral insufficiency fracture of the femoral head may be associated with hip
      dysplasia: a pilot study.
AB  - BACKGROUND: Subchondral insufficiency fracture of the femoral head occurs mainly
      in elderly patients with osteoporosis. Spontaneous resolution is observed after
      nonoperative treatment in some patients whereas other show progressive joint
      destruction requiring THA. Several studies report the occurrence of subchondral
      insufficiency fracture of the femoral head in dysplastic hips.
      QUESTIONS/PURPOSES: We asked whether the extent of hip dysplasia or osteoporosis
      was greater in patients with subchondral insufficiency fracture of the femoral
      head than in normal control subjects. PATIENTS AND METHODS: We compared the
      clinical and imaging findings of 13 patients with subchondral insufficiency
      fractures of the femoral head and 12 patients scheduled for TKA with asymptomatic
      hips. Age, gender, and body mass index were comparable in the two groups.
      RESULTS: Higher mean Sharp angles, lower acetabular head indices, lower center
      edge angles, and higher acetabular roof angles in patients with subchondral
      insufficiency fracture of the femoral head than in those with asymptomatic hips
      suggested a greater degree of hip dysplasia. Bone mineral density and serum
      levels of Type I collagen cross-linked N-telopeptide and bone alkaline
      phosphatase were similar in the two groups. CONCLUSIONS: We speculate an
      excessive amount of stress on the acetabular edge from dysplasia may be
      associated with the occurrence of subchondral insufficiency fracture of the
      femoral head.

PMID- 20058111
TI  - One-stage metatarsal lengthening by allograft interposition: a novel approach for
      congenital brachymetatarsia.
AB  - BACKGROUND: Congenital brachymetatarsia, a shortened metatarsal bone, can be
      corrected surgically by callus distraction or one-stage lengthening using bone
      graft. QUESTIONS/PURPOSES: We asked whether one-stage metatarsal lengthening
      using metatarsal homologous bone graft could improve forefoot function, lead to
      metatarsal healing, restore metatarsal parabola, and improve cosmetic appearance.
      PATIENTS AND METHODS: We retrospectively reviewed 29 patients (41 feet) in whom
      we lengthened 50 metatarsals. Surgery consisted of a transverse proximal
      osteotomy of the metatarsal shaft and interposition of a metatarsal homologous
      bone graft (average, 13 mm long) fixed with an intramedullary Kirschner wire.
      Minimum followup was 3 years (mean, 5 years; range, 3-11 years). RESULTS: Bone
      union was achieved in all cases. The mean preoperative American Orthopaedic Foot
      and Ankle Society score was 37 points (range, 28-53 points) and the mean
      postoperative score was 88 points (range, 74-96 points), with an average
      improvement of 51 points. Radiographically, the mean gain in length was 13 mm
      (range, 10-15 mm), and the mean percentage increase was 23%. CONCLUSIONS: One
      stage metatarsal lengthening using interposition of metatarsal homologous bone
      graft to correct congenital brachymetatarsia has low morbidity for the patient,
      limited complications, short recovery times, and restores forefoot anatomy. LEVEL
      OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 20058112
TI  - Midterm assessment of causes and results of revision total knee arthroplasty.
AB  - BACKGROUND: There is limited information regarding revision total knee
      arthroplasty (TKA) with respect to etiology, outcome, and long-term survival
      comparing different implant types. QUESTIONS/PURPOSES: We compared patient
      outcomes, survivorship and modes of failure and the most common etiologic factors
      for rerevision between different revision implant types. METHODS: We
      retrospectively reviewed 349 cases of revision TKA in 343 patients whose mean age
      was 67.8 years. Three implant types were used: posterior stabilized, condylar
      constrained knee, and rotating hinge. The etiologies included infection (32.7%),
      aseptic loosening (14.9%), and polyethylene wear (12.3%). The minimum followup
      was 12 months (mean, 57.7 months; range, 12-120 months). RESULTS: The mean Knee
      Society scores were 89 (range, 48-94), 88.9 (range, 45-95), and 84 (range, 56-94)
      and the mean ranges of motion were 110.0 degrees (range, 70 degrees -125 degrees
      ), 106.1 degrees (range, 70 degrees -120 degrees ), and 111.7 degrees (range, 85
      degrees -125 degrees ) for the posterior stabilized, condylar constrained knee,
      and rotating hinge types, respectively. The rotating hinge group had the highest
      satisfaction rates (88%). Overall 10-year survivorship was 90.6% with highest
      survivorship seen in the rotating hinge group. The most common causes for
      rerevision were infection (2.9% of our cohort), instability (1.7%), and aseptic
      loosening (1.4%). The mean overall time to rerevision was 69.9 months (range, 11
      119 months). CONCLUSIONS: In our experience periprosthetic infection is the most
      common cause of failure of both primary and revision TKA. Functional outcome and
      range of motion improve irrespective of revision implant type. The rotating hinge
      prosthesis provides patient satisfaction and survivorship similar to that of
      other implant types. LEVEL OF EVIDENCE: Level IV, therapeutic study. See
      Guidelines for Authors for a complete description of levels of evidence.

PMID- 20058113
TI  - Intranasal delivery of influenza subunit vaccine formulated with GEM particles as
      an adjuvant.
AB  - Nasal administration of influenza vaccine has the potential to facilitate
      influenza control and prevention. However, when administered intranasally (i.n.),
      commercially available inactivated vaccines only generate systemic and mucosal
      immune responses if strong adjuvants are used, which are often associated with
      safety problems. We describe the successful use of a safe adjuvant Gram-positive
      enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus
      lactis for i.n. vaccination with subunit influenza vaccine in mice. It is shown
      that simple admixing of the vaccine with the GEM particles results in a strongly
      enhanced immune response. Already after one booster, the i.n. delivered GEM
      subunit vaccine resulted in hemagglutination inhibition titers in serum at a
      level equal to the conventional intramuscular (i.m.) route. Moreover, i.n.
      immunization with GEM subunit vaccine elicited superior mucosal and Th1 skewed
      immune responses compared to those induced by i.m. and i.n. administered subunit
      vaccine alone. In conclusion, GEM particles act as a potent adjuvant for i.n.
      influenza immunization.

PMID- 20058114
TI  - The clinical use of right-sided double-lumen tubes.

PMID- 20058115
TI  - [Editorial: wrist joint encroachment].

PMID- 20058116
TI  - [NITINOL shape memory staple for osteosynthesis of the scaphoid].
AB  - OBJECTIVE: Reconstruction of the scaphoid with use of NITINOL shape "memory"
      staples. INDICATIONS: Unstable fractures and nonunion of the middle third of the
      scaphoid, which need open reduction and internal fixation from palmar. The
      staples can only be used, if the arms of the staples can be inserted parallel to
      and at a distance of 3 mm to the fracture line. CONTRAINDICATIONS: Allergy to
      nickel. Cases in which the arms of the staple cannot be inserted parallel to and
      at best 3 mm apart from the fracture line. SURGICAL TECHNIQUE: In fractures, open
      reduction of the scaphoid through a palmar approach. If necessary, interposition
      of a bone graft and Kirschner wire transfixation. Drilling of the drill holes
      parallel and at a distance of 3 mm to the fracture line. Insertion of the NITINOL
      staple. In nonunion, excision of the fibrous nonunion, refreshening of the
      fracture surfaces, interposition of a bone graft and, if needed, fixation with a
      Kirschner wire. Drilling of the drill holes for the NITINOL staple and insertion
      of the staple. Within a few minutes the warming-up staple contracts and thereby
      compresses the scaphoid. POSTOPERATIVE MANAGEMENT: Immobilization in a short cast
      with thumb support for 6 weeks. Control for bone healing by radiographs or
      computed tomography. Staples, which do not cause hardware problems, are not
      removed. Kirschner wires are removed after bone healing. RESULTS: From October
      1995 to December 2006, the authors used NITINOL staples for 65 osteosyntheses of
      the scaphoid. Indications were 15 unstable fractures, 47 nonunions, and three
      partial necroses. 61 out of 65 scaphoids healed without further surgery, three of
      the 61 patients showed a delayed healing. Two of the four nonunions were related
      to the use of the NITINOL staples. Seven staples were removed, one for loosening.
      NITINOL shape memory staples have proven to be very helpful for osteosynthesis in
      fractures and nonunion of the scaphoid, if the prerequisites are given for their
      use.

PMID- 20058117
TI  - [Pedicled vascularized bone grafts from the dorsum of the distal radius for
      treatment of scaphoid nonunions].
AB  - OBJECTIVE: Bony healing and reconstruction of the scaphoid with use of a reverse
      flow pedicle vascularized bone graft from the dorsal aspect of the distal radius.
      Revitalization of the proximal fragment in case of avascular necrosis.
      INDICATIONS: Scaphoid nonunion, especially of the proximal pole. Nonunion after
      failed attempts of autogenous nonvascularized bone grafting. Avascular necrosis
      of the scaphoid (Preiser's disease). Avascular osteonecrosis of other carpal
      bones (i.e., Kienbock's disease stage II and IIIa). However, these will not be
      addressed in this paper. CONTRAINDICATIONS: Advance carpal collapse (SNAC
      [scaphoid nonunion advanced collapse] wrist stage II and III). Avascular necrosis
      with broken proximal pole of the scaphoid. Malformation, disease or previous
      injury of the vascular system. SURGICAL TECHNIQUE: Reconstruction of the scaphoid
      by interposition of a vascularized bone graft from the dorsum of the distal
      radius, where several vascularized bone grafts can be harvested, and fixation by
      a scaphoid screw. POSTOPERATIVE MANAGEMENT: Management Immobilization for 6 weeks
      in a forearm cast including the first phalanx of the thumb. RESULTS: 48 scaphoid
      nonunions were treated with 1,2-ICSRA-based (intercompartmental supraretinacular
      artery) vascularized bone grafts: 34 scaphoid nonunions went on to union at an
      average of 15.6 weeks after surgery.

PMID- 20058118
TI  - [Free vascularized iliac bone graft for the treatment of scaphoid nonunion with
      avascular proximal fragment].
AB  - OBJECTIVE: The goal of the procedure is osseous healing of the scaphoid in an
      anatomic position and replacement of necrotic bone at the site of the scaphoid
      nonunion by a vascularized iliac bone graft. INDICATIONS: Scaphoid nonunion with
      necrotic fragment in SNAC (scaphoid nonunion advanced collapse) < 1. Nonunion
      following previous surgery. CONTRAINDICATIONS: Pattern of advanced carpal
      collapse (SNAC > 1). Malformation, disease or previous injury of the vascular
      system. Poor compliance. Reduced general health. SURGICAL TECHNIQUE: Principles
      of the surgical technique according to Pechlaner et al.: harvesting of a
      corticocancellous bone graft from the anterior iliac crest with a nutrient
      vascular bundle from the deep circumflex iliac artery, debridement of the
      necrotic scaphoid, press-fit fixation of the tailored graft, pin fixation, and
      microvascular anastomosis to the radial artery. POSTOPERATIVE MANAGEMENT:
      Fixation in an upper-arm cast for 4 weeks, followed by lower-arm cast fixation
      including the thumb to the interphalangeal joint until week 12. Physiotherapy.
      Wrist splinting in patients enforced to heavy manual load. RESULTS: The described
      procedure has been practiced at the own institution since 1985 and evaluated in
      different studies. Using a free vascularized iliac bone graft, union could be
      achieved in 85% of patients with avascular scaphoid nonunion and in 80% with
      avascular proximal pole nonunion. The nonunion can be bridged in 93% following
      failed previous scaphoid screw fixation.

PMID- 20058119
TI  - [Free microvascular transfer of segmental corticocancellous femur for the
      treatment of scaphoid nonunion].
AB  - OBJECTIVE: Reconstruction of the scaphoid in length and form. Revitalization of
      the proximal fragment in case of avascular necrosis. INDICATIONS: Nonunion of the
      scaphoid, especially with avascular necrosis of the proximal pole. Persisting
      nonunion of the scaphoid after operative treatment. CONTRAINDICATIONS: Pattern of
      advanced carpal collapse (SNAC > 1). Malformation, disease or previous injury of
      the vascular system. Low compliance. Reduced general health. SURGICAL TECHNIQUE:
      Reconstruction of the scaphoid in correct dimension and angulation with use of a
      vascularized microvascular corticocancellous bone graft from the medial distal
      femur. Anastomoses to the radial artery or its palmar branch. Fixation by a
      cannulated scaphoid screw or Kirschner wires. POSTOPERATIVE MANAGEMENT:
      Postoperative immobilization in a short cast with thumb support for 6 weeks
      followed by a removable splint for another 6 weeks. Physiotherapy after cast
      removal. RESULTS: 15 patients with avascular necrosis of the scaphoid were
      treated with this technique after a mean of 128 weeks following trauma. In five
      patients, one to three previous operations had already been performed. 6 months
      after surgery, osseous healing of the nonunion was registered in all patients.
      The carpal height ratio according to Nattrass was increased by 0.07. The
      scapholunate angle had decreased by 10.7 degrees on average. 14 patients had a
      mean improvement of the Mayo Wrist Score of 13.3 points.

PMID- 20058120
TI  - [Dorsal capsulodesis for the treatment of scapholunate instability].
AB  - OBJECTIVE: To regain stability of the proximal carpal row after scapholunate
      ligament rupture in order to avoid osteoarthritis and carpal collapse.
      INDICATIONS: As additional therapy in scapholunate ligament repair especially in
      patients with static, but reducible scapholunate malalignment. CONTRAINDICATIONS:
      Fixed scapholunate malalignment. Osteoarthritis of the radiocarpal or the
      midcarpal joint. SURGICAL TECHNIQUE: Dorsal approach to the carpal joint with
      release of the second, third and fourth extensor compartment and resection of the
      dorsal interosseous nerve. Opening of the radiocarpal joint for inspection of the
      chondral surfaces and the scapholunate ligament for possible repair. If needed,
      reduction of scaphoid and lunate. Repair of the scapholunate ligament. If a
      reduction of scaphoid and lunate is necessary, temporary Kirschner wire fixation
      of the scaphoid to the capitate and the lunate. The dorsal intercarpal ligament
      is identified and its middle third is dissected and elevated from the triquetrum
      remaining attached to the distal scaphoid pole. The ulnar end of the elevated
      part of the dorsal intercarpal ligament is pulled through a split in the dorsal
      radiotriquetral ligament and fixed to itself. Closure of the proximal and distal
      third of the dorsal intercarpal ligament. POSTOPERATIVE MANAGEMENT: Management
      Immobilization in a below-elbow cast including the metacarpophalangeal joint of
      the thumb for 6 weeks. Removal of the Kirschner wires, if used, 8 weeks
      postoperatively. Physiotherapy to improve wrist motion. RESULTS: Most of the
      reports in the literature show an improvement of pain. The effect on radiologic
      parameters and the development of osteoarthritis remains uncertain.

PMID- 20058121
TI  - [Treatment of chronic scapholunate dissociation using Cuenod's bone-ligament-bone
      autograft].
AB  - OBJECTIVE: Correction of chronic scapholunate dissociation by replacement of the
      biomechanically most important dorsal part of the scapholunate ligament using a
      bone-ligament-bone autograft taken from the carpometacarpal joint II and,
      additionally, a modified dorsal capsulodesis. INDICATIONS: Nonfixed chronic
      scapholunate dissociation without useful remnants of the ligament in which loss
      of the dorsal part of the scapholunate ligament is the crucial pathophysiological
      moment. CONTRAINDICATIONS: Chronic scapholunate dissociation with fixed
      deformity. Osteoarthritis. SURGICAL TECHNIQUE: Dorsal incision. Approach to the
      wrist using the capsular flap described by Berger. Reduction of deformity and
      temporary transfixation of the scaphoid to the capitate as well as to the lunate.
      Creation of a trough at the ulnar edge of the dorsal aspect of the scaphoid and
      another trough at the radial edge of the dorsal aspect of the lunate. Fixation of
      an exactly fitting bone-ligament-bone autograft taken from the
      trapezoidometacarpal joint II with 1.2-mm screws into the troughs. Fixation of a
      part of the dorsal intercarpal ligament which is based on the scaphoid to the
      lunate using a bone anchor. POSTOPERATIVE MANAGEMENT: Immobilization using a
      below-elbow cast including the metacarpophalangeal joint of the thumb for 8
      weeks; removal of Kirschner wires 10 weeks postoperatively; after Kirschner wire
      removal physiotherapy to improve range of motion. RESULTS: Twelve out of 16 male
      patients were available for a clinical and radiologic examination after a mean
      follow-up time of 6.3 years (minimum 1.6, maximum 7.3 years). Clinical results
      were excellent. The modified Mayo Wrist Score averaged 87 points (minimum 65,
      maximum 100 points). Eleven patients had an excellent or good result, none of the
      patients showed a poor result. The DASH Score (Disability of the Arm, Shoulder
      and Hand) was 13 points on average (minimum 0, maximum 42 points). All patients
      would have the same operation again. Radiologically, a stretching of the bone
      ligament-bone autograft was found in six cases. A symptomatic SLAC (scapholunate
      advanced collapse) wrist with the need for a salvage operation could not be
      observed.

PMID- 20058122
TI  - [Stabilization of the scaphoid according to Brunelli as modified by Garcia-Elias,
      Lluch, and Stanley for the treatment of chronic scapholunate dissociation].
AB  - OBJECTIVE: Stabilization of the scaphoid correcting rotary subluxation and
      replacement of the biomechanically essential dorsal part of the scapholunate
      ligament for prevention of osteoarthritis. INDICATIONS: Scapholunate dissociation
      without useful remnants of the ligament and reducible malalignment of the
      scaphoid. CONTRAINDICATIONS: Fixed scaphoid malalignment. Osteoarthritis (SLAC
      [scapholunate advanced collapse] wrist). SURGICAL TECHNIQUE: Dorsal approach to
      the wrist using the flap described by Berger. Correction of rotary subluxation
      and stabilization of the scaphoid using a distally based strip of flexor carpi
      radialis tendon, which is created through a separate palmar incision, and fixed
      to a bone anchor in the lunate through a tunnel from the palmar side of the
      distal pole of the scaphoid to the origin of the dorsal part of the scapholunate
      ligament from the scaphoid combined with transfixation of the scaphoid to the
      capitate and the lunate bone in corrected position using two Kirschner wires (1.6
      mm). Additionally, the flexor carpi radialis strip is looped through a split in
      the dorsal radiotriquetral ligament and fixed to itself. POSTOPERATIVE
      MANAGEMENT: Immobilization using a below-elbow cast including the
      metacarpophalangeal joint of the thumb for 6 weeks. Removal of the Kirschner
      wires 8 weeks postoperatively, followed by physiotherapy to improve wrist motion.
      RESULTS: 14 out of 17 patients were available for a clinical and radiologic
      examination after a mean follow-up time of 10.5 months (minimum 6, maximum 15
      months). Two of these patients had to undergo another operative procedure in the
      meantime, one partial and the other total wrist fusion. The remaining twelve
      patients had a mean DASH Score (Disabilities of the Arm, Shoulder and Hand) of 25
      (minimum 0, maximum 59 points) and a mean modified Mayo Wrist Score of 80 points
      (minimum 60, maximum 97 points). Contrary to the good clinical results, the final
      radiologic examination demonstrated a tendency toward loss of correction compared
      to the postoperative X-rays.

PMID- 20058123
TI  - [Stabilization of perilunate and transscaphoid perilunate fracture-dislocations
      via a combined palmar and dorsal approach].
AB  - OBJECTIVE: Restoration of the intercarpal alignment and the radio- and ulnocarpal
      joint in order to avoid the development of a carpal collapse with concomitant
      arthritis of the radiocarpal and midcarpal joint. INDICATIONS: All perilunate and
      transscaphoid perilunate fracture-dislocations. An exception is a pure
      ligamentous injury with anatomic carpal alignment following closed reduction
      (computed tomography scan). CONTRAINDICATIONS: General contraindications to an
      operative procedure. SURGICAL TECHNIQUE: It is crucial that all involved bony and
      ligamentous structures are addressed, using a bilateral approach. Depending on
      their location, scaphoid fractures are stabilized from proximal or distal, and
      bony avulsions are fixed at their origin. The typical rent across the palmar
      ligaments is closed, and the avulsed scapholunate ligament and the dorsal
      intercarpal ligament are reattached to the adjacent bones. Temporary Kirschner
      wire fixation is essential for healing. POSTOPERATIVE MANAGEMENT: Forearm plaster
      cast with short thumb for 12 weeks. Kirschner wire removal after 8 weeks.
      RESULTS: 25 patients (15 perilunate dislocations and ten perilunate fracture
      dislocations) could be included for follow-up 5 years after the trauma.
      Perilunate fracture-dislocations achieved slightly better results than perilunate
      dislocations. The DASH Score (Disability of the Arm, Shoulder and Hand) averaged
      11.3 and 14.2 points, the PRWE Score (Patient- Related Wrist Evaluation) 20.7 and
      27.7 points, respectively. The Mayo Wrist Score amounted to 81.5 and 82.7 points.
      Active range of wrist motion was reduced by one third compared with the opposite
      side. Grip strength was reduced by 15-20%. The pain level ranged between 2 and 4
      on a scale from 0 to 10. In pure ligamentous injuries, degenerative arthritis was
      more common in the midcarpal joint, whereas radiocarpal arthritis predominated in
      the fracture-dislocation group.

PMID- 20058124
TI  - [Fixation of fractures of the distal radius using the "nail-plate"].
AB  - OBJECTIVE: Stable fixation of unstable distal radius fractures by means of a
      "nail-plate" with the distal plate section lying on the dorsal surface of the
      distal radius fragment, and the proximal nail section inside the diaphysis of the
      radius. INDICATIONS: Unstable extraarticular fractures of the distal radius AO
      types A2 and A3, which can be managed by closed or indirect reduction.
      Intraarticular fractures of the distal radius showing a nondisplaced articular
      component. Also indicated in patients with osteoporosis. CONTRAINDICATIONS:
      Extraarticular distal radius fractures with a distal fragment too small for
      placement of the distal locking pegs and/or a comminution extending into the
      diaphyseal portion of the radius. Displaced intraarticular fractures of the
      distal radius. Nascent malunions of the distal radius. SURGICAL TECHNIQUE: Closed
      reduction of the fracture, straight dorsal incision of 3-4 cm length centered
      over Lister's tubercle. The extensor pollicis longus tendon is released and
      retracted toward the radial side. Lister's tubercle is exposed subperiosteally
      and removed with a rongeur. This creates a flat surface for seating the head of
      the implant. Proximal dissection is carried out to expose the fracture site and
      the dorsal ridge on the proximal fragment. The medullary canal is opened with an
      awl. The radiocarpal joint line is located by inserting a needle. The silhouette
      of the head of the implant is drawn with a marker pen, with its distal edge
      resting 4-6 mm proximal to the joint line. This is done to carve a notch on the
      distal edge of the proximal fragment in line with the third extensor compartment
      with the purpose of receiving the neck of the device. The insertion jig is
      assembled to the implant. The implant is then introduced in a retrograde fashion,
      through the fracture site, into the proximal fragment and advanced with gentle
      rotational motion. The head of the device is seated flush on the distal fragment.
      Under fluoroscopic guidance, in an anatomic lateral view, the tract for the
      central peg is drilled and the peg is applied in the central hole. This peg fixes
      the palmar tilt. By use of the jig, the proximal unicortical holes are drilled,
      and the proximal locking screws, which fix the radial length, are applied. After
      removal of the insertion jig, the remaining distal pegs are applied. During
      drilling, the distal fragment must be pushed up against the implant to assure
      that the head is flush with its surface. After application, the extensor pollicis
      longus tendon will course proximal to the head of the implant in the subcutaneous
      position while the tendons of the second and fourth extensor compartments will
      travel on each side of the implant, thereby avoiding tendon impingement.
      POSTOPERATIVE MANAGEMENT: Use of a palmar synthetic splint for 10 days. Active
      range of motion of the fingers is allowed immediately after surgery. On the 11th
      postoperative day, a custom-formed short arm splint is provided and active wrist
      motion is started. Radiologic control 4 weeks postoperatively. RESULTS: In the
      time between April 2005 and October 2006, 32 distal radius fractures were treated
      at the author's institution using the "nail-plate". Two complications were
      observed: loosening of a locking screw, and rupture of the extensor pollicis
      longus tendon 4 months postoperatively. In a study of more than 200 cases, only
      few complications were reported: a wound hematoma in a dialysis patient, loss of
      fixation of an articular fracture that was poorly indicated, and hypertrophic
      scar formation. In one patient complaining of persistent discomfort at the
      implantation site, the implant was removed.

PMID- 20058125
TI  - [Fixation of distal radial fractures with the Targon DR nail].
AB  - OBJECTIVE: Anatomic restoration and intramedullary fixation of distal radial
      fractures using a hybrid between plate and nail (Targon DR). The technique
      provides a less invasive operative approach from radial. INDICATIONS:
      Extraarticular fractures of the distal radius with dorsal comminution.
      Intraarticular fractures without displacement and with a sagittal fracture line.
      CONTRAINDICATIONS: Flexion fractures, intraarticular fractures with displacement
      of the articular surface or a frontal fracture line. SURGICAL TECHNIQUE: 4-cm
      skin incision from the tip of the radial styloid. Careful dissection of the
      superficial branch of the radial nerve. Preparation of the bone between first and
      second extensor compartment. Reduction of the fracture, insertion of a Kirschner
      wire from the tip of the styloid across the fracture line. Opening of the
      intramedullary canal with a cannulated drill using the Kirschner wire as a guide.
      Stepwise widening of the intramedullary canal with profilers. Implantation of the
      Targon DR device. Interlocking using an aiming jig. Replacement of Kirschner
      wires by screws, removal of the aiming jig, and wound closure. POSTOPERATIVE
      MANAGEMENT: Palmar splint for 2-14 days. Immediate functional after treatment.
      Full weight bearing 6 weeks after surgery. RESULTS: From December 2006 to May
      2008, 103 patients were treated with a Targon DR nail. 95 patients experienced
      the 8-week follow-up, 50 patients the 1-year follow-up. The mean time for surgery
      was 41.7 +/- 6.1 min. All fractures united. Radiologic analysis revealed a mean
      palmar tilt of 2.05 degrees +/- 0.67 degrees , radial length in relation to the
      ulna was adequately restored (0.06 +/- 0.05 mm difference compared to the
      uninjured side). As soon as 8 weeks after surgery the arc of extension/flexion
      reached 80% of the uninjured side. Mean Gartland-Werley Score 1 year after
      surgery was excellent (1.53 +/- 0.41).

PMID- 20058126
TI  - [The hemiresection-interposition arthroplasty of the distal radioulnar joint].
AB  - OBJECTIVE: Restoration of forearm rotation and pain relief at the distal
      radioulnar joint by resection of the joint surfaces of the ulnar head,
      interposition of a capsular-retinacular flap, and preservation or reconstruction
      of the ulnocarpal complex. INDICATIONS: Painful osteoarthritis of the distal
      radioulnar joint. CONTRAINDICATIONS: Longitudinal instability in the forearm,
      e.g., Essex-Lopresti lesions or after radial head resection. Posttraumatic ulnar
      subluxation of the carpus. SURGICAL TECHNIQUE: Exposition of the distal
      radioulnar joint via the floor of the fifth extensor compartment and preparation
      of an ulnarbased capsular-retinacular flap. Preservation of the fourth and sixth
      extensor compartment. Resection of the jointbearing areas of the ulnar head
      preserving the ulnar styloid and the triangular fibrocartilage complex (TFCC). If
      necessary, refixation or reconstruction of the TFCC. Interposition of the
      capsular-retinacular flap between the distal radius and ulna. Stabilization of
      the distal ulna by suture fixation of the dorsal part of the flap to the dorsal
      rim of the sigmoid notch. POSTOPERATIVE MANAGEMENT: Immobilization in a long arm
      cast with 45 degrees forearm supination for 4 weeks. Afterwards, forearm
      pronation and supination are further limited for 4 weeks by a splint. Following
      that period, the range of motion and the load are raised to normal levels.
      RESULTS: The hemiresection-interposition arthroplasty of the distal radioulnar
      joint improves the range of forearm rotation. Pain is significantly reduced and
      grip strength increased. Instability of the distal ulna may persist or result;
      however, this gives rise to moderate complaints only in some patients. Patients'
      satisfaction is high and the functional results are good.

PMID- 20058127
TI  - [Total wrist fusion using the AO wrist fusion plate].
AB  - OBJECTIVE: Arthrodesis of the wrist in order to improve functional use of the
      hand by reducing pain and improving grip strength. INDICATIONS: Painful
      destruction of both the radiocarpal and mediocarpal joint combined with
      contraindications to motion-preserving procedures. Conservative treatment
      insufficient. CONTRAINDICATIONS: Patients who are pain-free and satisfied with a
      motion-preserving procedure (e.g., Wilhelm's denervation procedure) or
      conservative management (casting). SURGICAL TECHNIQUE: Dorsal approach to the
      wrist. Removal of destroyed articular surfaces down to cancellous bone, filling
      the resulting defects with cancellous bone graft taken either from the the radius
      or the iliac crest. Stable fixation using the AO wrist fusion plate.
      POSTOPERATIVE MANAGEMENT: Immediate active motion exercises of the fingers. Below
      elbow cast for 2 weeks. 6 weeks postoperatively, X-ray control to judge bony
      healing. Normal use of the hand in daily life but avoiding pain-provoking
      activities. RESULTS: 26 (18 men, eight women) of the authors' first patients with
      arthrodesis of the wrist using the AO fusion plate were reexamined after a mean
      follow-up time of 18 months (minimum 6, maximum 32 months). The mean modified
      Mayo Wrist Score was 47 points (minimum 20, maximum 70 points), the DASH Score
      (Disabilities of the Arm, Shoulder and Hand) averaged 46 points (minimum 4,
      maximum 81 points). 20 of the 26 patients were satisfied, but not all patients
      were completely free of pain. Eight out of a total of ten patients (seven men,
      three women) with a bilateral wrist arthrodesis were reexamined after a mean
      follow-up time of 66 months (minimum 27, maximum 74 months). The DASH Score was
      55 points on average (minimum 38, maximum 73 points). All patients stated that
      their clinical situation had improved and that they were able to manage their
      daily activities without help. So it can be concluded that bilateral arthrodesis
      of the wrist is a valuable option, if all other possibilities are exhausted.

PMID- 20058128
TI  - [Plaster of Paris in hand surgery].
AB  - Immobilization is as essential to conservative treatment of the hand as it is
      perioperatively in surgical treatment. Low cost and outstanding moldability
      distinguish plaster of Paris. This paper surveys frequently used applications of
      plaster of Paris in hand surgery.

PMID- 20058134
TI  - Importance of follow-up inspection after pulmonary angioplastic procedures for
      lung cancer surgery.

PMID- 20058129
TI  - Joint quality improvement guidelines for pediatric arterial access and
      arteriography: from the Societies of Interventional Radiology and Pediatric
      Radiology.

PMID- 20058135
TI  - UFT and S-1 for treatment of primary lung cancer.
AB  - UFT and S-1 are oral 5-fluorouracil (5-FU) derivative drugs containing an
      inhibitor of dihydropyrimidine dehydrogenase (DPD); they are defined as DPD
      inhibitory fluoropyrimidine (DIF). Because DPD is the key enzyme of 5-FU
      degradation, 5-FU is not active in primary lung cancers with high DPD activity,
      which causes rapid degradation of 5-FU. Thus, theoretically, a DIF can overcome a
      cancer's resistance to 5-FU through inhibiting the enzyme activity of DPD, with
      the result that 5-FU may be active in primary lung cancer. In fact, UFT has
      proved to be effective in a postoperative adjuvant setting for early non-small
      cell lung cancer (NSCLC) in several randomized controlled studies (RCTs). S-1, in
      which a more potent DPD inhibitor is combined, is active in advanced NSCLC
      regardless of the histological cell subtype, and its clinical efficacy in first
      line therapy for unresectable advanced disease as well as in postoperative
      adjuvant therapy for resected disease is now being examined in a variety of RCTs.
      In the present review, the mechanism of action of UFT and S-1 as well as clinical
      evidence regarding their use in the treatment of NSCLC are summarized.

PMID- 20058136
TI  - Expanded polytetrafluoroethylene-valved conduit with bulging sinuses for right
      ventricular outflow tract reconstruction in adults.
AB  - PURPOSE: Generally, right ventricular outflow tract reconstruction in adults is
      performed using homografts or xenograft. However, sufficient graft material is
      difficult to obtain and has the problems of calcification and structure
      destruction. We, therefore, evaluated using expanded polytetrafluoroethylene-
      (ePTFE)-valved conduits with bulging sinuses for right ventricular outflow tract
      reconstruction in adults. METHODS: Between February 2006 and April 2008, a total
      of five patients (three men, two women), ages 25-51 years old (mean +/- SD, 40 +/
      11 years)] underwent right ventricular outflow tract (RVOT) reconstruction in
      our institution. In three patients, RVOT reconstruction was performed with the
      Ross procedure; and in all cases, tricuspid ePTFE (valved conduits with bulging
      sinuses were used. The diameter of the conduit was determined according to the
      RVOT size. Valve function was followed up using echocardiography after surgery
      and during the early/mid-term periods of recovery (13 months to 3.0 years).
      RESULTS: No morbidity occurred, and no patient required further surgery during
      the follow-up period. During these follow-up periods, pulmonary observation
      revealed that no patients had stenosis; regurgitation was mild in one patient and
      trivial in four patients. In regard to the tricuspid valve, regurgitation was
      trivial in four patients and mild in one patient. CONCLUSION: Although long-term
      follow-up is required to confirm the durability of the ePTFE-valved conduit with
      bulging sinuses, the present results indicate a satisfactory result in patients
      who undergo RVOT reconstruction, even in adult cases.

PMID- 20058137
TI  - Pulmonary angioplastic procedure for lung cancer surgery.
AB  - PURPOSE: Although bronchoplasty for the treatment of lung cancer is widely
      accepted as a reliable, safe procedure for the preservation of lung function,
      there have been only a few reports on pulmonary artery (PA) resection and
      reconstruction. METHODS: Retrospectively, we reviewed our medical records of
      pulmonary angioplastic procedures and assessed the results. RESULTS: A total of
      25 patients (5 women, 20 men) with a mean age of 68 years (range 44-85 years)
      underwent a pulmonary angioplastic procedure for lung cancer surgery. Altogether,
      13 patients had adenocarcinoma, and 11 had squamous cell carcinoma. The cancers
      were located in the left lung in 15 cases and in the right lung in 10 cases. The
      PA reconstructions comprised 4 circumferential resections and anastomoses, 18
      wedge resections and end-to-end anastomoses, 2 tangential resections with direct
      suturing, and 1 wide wedge resection and autologous pericardial patch repair. Six
      patients underwent concomitant bronchoplasty with pulmonary artery
      reconstruction. Prior to surgical treatment, seven patients had received
      neoadjuvant therapy. Although early postoperative complications occurred in eight
      patients (32%), no operative or in-hospital deaths occurred. All the patients in
      this series were discharged from hospital and went home. The overall 5-year
      survival rate was 45%, with a mean 27 months of follow-up. CONCLUSION: Most
      operative complications after PA reconstruction were controllable despite the
      high morbidity rate. Pulmonary angioplastic procedures for the surgical treatment
      of lung cancer are both useful and feasible with good intermediate-term results.

PMID- 20058138
TI  - Bilateral lung transplantation with closure of ventricular septal defect in a
      patient with Eisenmenger syndrome.
AB  - We report the first case with Eisenmenger syndrome secondary to an isolated
      perimembranous ventricular septal defect (VSD) in a patient who underwent
      bilateral lung transplantation and closure of the VSD in Japan. This male patient
      was diagnosed as having a VSD associated with severe pulmonary hypertension at
      the age of 7, and right unilateral pulmonary artery banding was performed at age
      9. At 38 years of age, we performed bilateral cadaveric lung transplantation with
      patch closure of the VSD. Explant pathology revealed grade 3 for the right lung
      and grade 4 for the left lung by the Heath-Edwards classification. The
      ventricular contractility had gradually improved, and ventricular arrhythmia
      requiring amiodarone prior to lung transplantation had disappeared. When cardiac
      function is preserved, bilateral lung transplantation is an option for patients
      with Eisenmenger syndrome secondary to VSD and should be considered as an
      alternative to heart-lung transplantation, especially in Japan, where donor organ
      shortage is critical.

PMID- 20058139
TI  - Pulmonary hamartoma treated by thoracoscopic enucleation.
AB  - We recommend thoracoscopic enucleation with the aid of a video-assisted thoracic
      surgery marker to treat pulmonary hamartoma, even when it stays in the center of
      pulmonary lobe. We report how we were able to enucleate a pulmonary hamartoma
      safely and manage the patient during hospitalization.

PMID- 20058140
TI  - Obstructive prosthetic atrioventricular valve thrombosis in a woman with
      congenitally corrected transposition of the great arteries during estrogen
      replacement therapy for pituitary dysfunction.
AB  - A 27-year-old woman was admitted because of breathlessness, orthopnea, and
      hemoptysis. The present patient was diagnosed with congenitally corrected
      transposition of the great arteries (cc-TGA) and underwent systemic
      atrioventricular valve replacement for severe insufficiency at 23 years of age.
      She also had been treated with oral conjugated equine estrogen (Premarin) because
      of congenital pituitary dysfunction. Despite appropriate anticoagulation therapy
      with warfarin, echocardiography and fluoroscopy showed stuck leaflets of the
      prosthetic valve due to thrombosis. She underwent emergent surgical valve
      replacement. This rare association suggests that oral hormone replacement therapy
      poses a risk of thrombosis especially in patients with cc-TGA after prosthetic
      valve replacement.

PMID- 20058141
TI  - Thymoma concomitant with a right aortic arch.
AB  - A 63-year-old woman was referred to our hospital because screening had detected
      an anterior mediastinal tumor with a right aortic arch. She underwent typical
      total thymectomy via a median sternotomy but developed left recurrent laryngeal
      nerve (RLN) palsy postoperatively. The pathology examination revealed that the
      tumor was a stage I thymoma. This is the first report of a thymoma with a right
      aortic arch. The left RLN goes around the left ductus arteriosus, which connects
      the origin of the left subclavian artery to the left pulmonary artery. The RLN
      was likely to be injured in the neighborhood of the left ductus arteriosus when
      the tumor and thymus were dissected over the pulmonary artery. During operations
      for an anterior mediastinal tumor with a right aortic arch, we should be
      attentive to the location of the tumor, the left ductus arteriosus, and the left
      RLN.

PMID- 20058142
TI  - Anterior chest wall giant cell tumor.
AB  - Giant cell tumors (GCTs) of bone are rare primary neoplasms that usually
      originate from the epiphysis of long bones. Even when the tumor occurs in a rib,
      it is usually in the posterior aspect. We report a case of a GCT originating from
      the anterior arc of the rib in a 22-year-old woman presenting with a
      progressively growing thoracic mass in the right anterior chest wall. Through
      this case the authors emphasize not only the rarity of a bone GCT but also its
      unusual costal localization.

PMID- 20058143
TI  - Retained foreign body following pleural drainage with a small-bore catheter.
AB  - Small-bore radiopaque drains can be used to drain pleural effusions. They offer
      reliable drainage of simple pleural effusions and provide a safe, less-invasive,
      more comfortable alternative to the standard tube thoracostomy. Importantly,
      removal of such drains does not require purse-string sutures and hence can be
      removed without assistance. We report here the cautionary tale of a retained
      foreign body related to drainage of a pleural effusion with a Pleurocath in a
      patient following cardiac surgery to raise awareness of this potential
      complication. Emphasized is the need for all staff to be familiar with the normal
      appearance of equipment being utilized in the ward and to report when incomplete
      removal of drain equipment is suspected. In addition, amendments to insertion
      techniques for such small-bore drains are proposed to avoid similar undue
      complications.

PMID- 20058144
TI  - Aortocavitary fistula without aneurysm and transient incomplete atrioventricular
      block due to infective endocarditis.
AB  - A 67-year-old man with persistent fever and moderate aortic valve regurgitation
      was transferred. He suffered from incomplete atrioventricular block (AVB), and
      temporary pacing was needed. Left-to-right shunt flow from the aorta to the right
      atrium was found without an aneurysm. Operative findings indicated that the
      aortic valve was highly calcified. The orifice of an aortocavitary fistula (ACF)
      was detected in the sinus of Valsalva and the right atrium. Patch repair of the
      aortic annulus with complete debridement of the abscess cavity was performed, a
      procedure that consisted of aortic valve replacement directly to the Gore-Tex
      patch and aortic root replacement. His postoperative course was uneventful, but a
      pacemaker was implanted owing to complete AVB. To our knowledge, this is a rare
      case in which infective endocarditis was complicated by ACF without an aneurysm
      of the sinus of valsalva (SV) on the noncoronary cusp to the right atrium and
      transient incomplete AVB (Mobitz type II) occurring simultaneously.

PMID- 20058145
TI  - Active infective endocarditis after mitral valve repair.
AB  - A 22-year-old man was diagnosed with active mitral endocarditis 14 months after
      mitral valve repair. The responsible organism was methicillin-resistant
      Staphylococcus epidermidis. Transthoracic echocardiography showed an 8-mm patch
      of vegetation adhering to the anterior part of the artificial ring. Although
      antibiotics (piperacillin, minocycline, imipenem/cilastatin, and ampicillin) were
      administered, the vegetation grew to 30 mm. Reoperation was performed 35 days
      after the diagnosis. Before surgery, there was mild mitral regurgitation without
      congestive heart failure. Re-repair was performed by removing the vegetation and
      the artificial ring, and mattress sutures repaired the circumferential sulcus
      formed by the artificial ring. Teicoplanin and minocycline were administered for
      6 weeks. At 20 months, infective endocarditis was absent. Residual mitral
      regurgitation has been consistently mild. Although active mitral endocarditis
      after mitral valve repair is rare, prompt reoperation should be considered if the
      responsible organism is drug-resistant and infection spreads to the artificial
      ring.

PMID- 20058146
TI  - Transcriptome analysis of resistant and susceptible genotypes of Glycine
      tomentella during Phakopsora pachyrhizi infection reveals novel rust resistance
      genes.
AB  - Soybean rust, caused by Phakopsora pachyrhizi, is a destructive foliar disease in
      nearly all soybean-producing countries. To identify genes controlling resistance
      to soybean rust, transcriptome profiling was conducted in resistant and
      susceptible Glycine tomentella genotypes triggered by P. pachyrhizi infection.
      Among 38,400 genes monitored using a soybean microarray, at 5% false discovery
      rate, 1,342 genes were identified exhibiting significant differential expression
      between uninfected and P. pachyrhizi-infected leaves at 12, 24, 48, and 72 h post
      inoculation (hpi) in both rust-susceptible and rust-resistant genotypes.
      Differentially expressed genes were grouped into 12 functional categories, and
      among those, large numbers relate to basic plant metabolism. Transcripts for
      genes involved in the phenylpropanoid pathway were up-regulated early during rust
      infection. Similarly, genes coding for proteins related to stress and defense
      responses such as glutathione-S-transferases, peroxidases, heat shock proteins,
      and lipoxygenases were consistently up-regulated following infection at all four
      time points. Whereas, subsets of genes involved in cellular transport, cellular
      communication, cell cycle, and DNA processing were down-regulated. Quantitative
      real-time reverse-transcription polymerase chain reaction (qRT-PCR) on randomly
      selected genes from the different categories confirmed these findings. Of
      differentially expressed genes, those associated with the flavonoid biosynthesis
      pathway as well as those coding for peroxidases and lipoxygenases were likely to
      be involved in rust resistance in soybean, and would serve as good candidates for
      functional studies. These findings provided insights into mechanisms underlying
      resistance and general activation of plant defense pathways in response to rust
      infection.

PMID- 20058147
TI  - Soybean seed lipoxygenase genes: molecular characterization and development of
      molecular marker assays.
AB  - Soybean seeds contain three lipoxygenase (Lox) enzymes that are controlled by
      separate genes, Lox1, Lox2 and Lox3. Lipoxygenases play a role in the development
      of unpleasant flavors in foods containing soybean by oxidation of polyunsaturated
      fatty acids. Null alleles for all three enzymes have been identified, lox1, lox2
      and lox3, and are known to be inherited as simple recessive alleles. Previous
      studies determined that a missense mutation rendered Lox2 inactive; however, the
      genetic cause of either lox1 or lox3 mutation was not known. The objectives of
      this study were the molecular characterization of both lox1 and lox3 mutant
      alleles and the development of molecular markers to accelerate breeding for Lox
      free soybean varieties. We identified two independent mutant alleles as the
      genetic causes of the lack of Lox1 in seeds of two lox1 mutant soybean lines.
      Similarly, a mutant allele that truncates Lox3 in a lox3 mutant soybean line was
      identified. Molecular markers were designed and confirmed to distinguish mutant,
      wild type, and heterozygous individuals for Lox1, Lox2 and Lox3 genes. Genotype
      and Lox phenotype analysis showed a perfect association between the inheritance
      of homozygous lox mutant alleles and the lack of Lox activity. Molecular
      characterization of a seed-lipoxygenase-free soybean line led to the discovery
      that an induced recombination event within the Lox1 gene was responsible for
      breaking the tight linkage in repulsion phase between mutant alleles at the Lox1
      and Lox2 loci. The molecular resources developed in this work should accelerate
      the inclusion of the lipoxygenase-free trait in soybean varieties.

PMID- 20058148
TI  - Factors associated with PISQ-12 completion in an academic urogynecology
      population.
AB  - INTRODUCTION AND HYPOTHESIS: Some new urogynecology patients who are given the
      Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ
      12) complete it despite stating that they are not sexually active. This study
      compared sexually active (SA) and non-sexually active (NSA) women who complete
      the PISQ-12, hypothesizing that these groups differ substantially. METHODS: New
      patients during the study period were given the PISQ-12 and two other validated
      questionnaires. Medical and demographic data were collected and analyzed for
      univariate differences between SA and NSA PISQ-12 completers. Logistical
      regression identified factors predicting PISQ-12 completion. RESULTS: Of the 655
      new patients during the study period, 399 completed the PISQ-12. Of these, 16.8%
      were NSA. These women were older, less likely married, and had higher BMI than
      their SA counterpart. Being sexually active, younger, and married are predictors
      of PISQ-12 completion. CONCLUSIONS: Some NSA women complete the PISQ-12.
      Instructions should specify that only SA women complete this questionnaire.

PMID- 20058150
TI  - Anatomic outcomes of abdominal sacrocolpopexy  with or without paravaginal
      repair.
AB  - INTRODUCTION AND HYPOTHESIS: We sought to compare rates of recurrent cystocele
      following sacrocolpopexy with and without paravaginal repair (PVR). METHODS: This
      retrospective cohort study compared outcomes for patients undergoing
      sacrocolpopexy with (group A) and without (group B) concomitant PVR. Defining
      anterior failure as point Ba > or = -1 cm, we compared anatomic outcomes and
      reoperation rates for recurrence of cystocele. RESULTS: One hundred seventy
      patients undergoing sacrocolpopexy had anterior wall prolapse at or beyond the
      hymen before surgery (62 in group A and 108 in group B). Ten (16.1%) patients in
      group A and 29 (26.9%) in group B experienced anterior wall prolapse to or beyond
      -1 cm (p = 0.13, power 0.38). Among these groups, one (1.6%) and five (4.6%)
      underwent reoperation for cystocele recurrence (p=0.42, power <0.3). CONCLUSIONS:
      Despite the trend toward improved clinical outcomes, we were unable to detect a
      statistically significant difference with inclusion of PVR with sacrocolpopexy.

PMID- 20058151
TI  - Environmental constraints modify the way an interceptive action is controlled.
AB  - This study concerns the process by which agents select control laws. Participants
      adjusted their walking speed in a virtual environment in order to intercept
      approaching targets. Successful interception can be achieved with a constant
      bearing angle (CBA) strategy that relies on prospective information, or with a
      modified required velocity (MRV) strategy, which also includes predictive
      information. We manipulated the curvature of the target paths and the display
      condition of these paths. The curvature manipulation had large effects on the
      walking kinematics when the target paths were not displayed (informationally poor
      display). In contrast, the walking kinematics were less affected by the curvature
      manipulation when the target paths were displayed (informationally rich display).
      This indicates that participants used an MRV strategy in the informationally rich
      display and a CBA strategy in the informationally poor display. Quantitative fits
      of the respective models confirm this information-driven switch between the use
      of a strategy that relies on prospective information and a strategy that includes
      predictive information. We conclude that agents are able of taking advantage of
      available information by selecting a suitable control law.

PMID- 20058152
TI  - Should routine analysis of the MEN1 gene be performed in all patients with
      primary hyperparathyroidism under 40 years of age?
AB  - BACKGROUND: Familial hyperparathyroidism, especially Multiple Endocrine Neoplasia
      Type 1, is more likely to present with primary hyperparathyroidism (1 degrees
      HPT) at a young age, mandating bilateral exploration of the parathyroid glands.
      However, the majority of young patients will not be gene carriers or have a
      family history. Recent evidence suggests that young adults under 40, in whom
      there is no suspicion of family history, can be managed with the same pre- and
      perioperative strategy as used for sporadic primary HPT of any age. Our aim was
      to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40
      who present with apparent sporadic 1 degrees HPT. METHODS: A retrospective review
      was undertaken of all patients who underwent surgery for 1 degrees HPT between
      1993 and 2004. From a total of 1253 patients, 87 (6.2%) were under the age of 40.
      Thirty-three patients provided informed consent to a detailed personal and family
      history, physical examination, and genetic analysis of the MEN1 gene. Twelve
      patients were subsequently excluded as they were known gene carriers prior to
      surgery (10 MEN1 and 2 MEN2A patients). Twenty-one patients underwent genetic
      analysis. RESULTS: Of the 21 patients who consented to genetic analysis, the mean
      age was 30.8 years (range = 18-39 years with 43% younger than 30). These patients
      had no suspicious family or personal histories suggestive of a MEN phenotype.
      Fifteen patients presented with symptomatic hypercalcemia. All 21 patients
      underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic
      parathyroidectomy in cases (9) where the parathyroid gland was localized
      preoperatively. Nineteen patients (91%) had uniglandular disease. Surgical cure
      was achieved in all patients. Of the 21 patients, only one patient (4.7%) was
      found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC).
      This patient was found to have double adenomas at surgery with subsequent
      histological confirmation. The overall prevalence of MEN1 mutation in all
      patients under 40 was 13%. CONCLUSION: Although young age is often the only
      criterion to suspect MEN1, our results do not support routine MEN1 analysis in
      patients under 40. We propose that these patients be managed with the same
      preoperative and surgical approach as those presenting with sporadic 1 degrees
      HPT of any age.

PMID- 20058153
TI  - [Mesenchymal tumors of skin and soft tissues: new entities and concepts].

PMID- 20058154
TI  - Necrotizing otitis externa: 19 cases' report.
AB  - Necrotizing otitis externa is an uncommon but severe infectious disease of the
      external auditory canal. Patients at risk are those immunodepressed or having
      diabetes. The causal germ is often Pseudomonas aeruginosa. Over a period of 10
      years (1997-2006), we treated 19 patients: 94.7% had diabetes (insulin dependent
      in 6 cases). The causal germ was P. aeruginosa in 59% of cases. The
      pretherapeutic work-up included a computed tomography and a scintigraphy
      practiced in order to confirm diagnosis and assess the extension. Medical
      treatment was based on a parenteral antibiotic therapy using a third-generation
      cephalosporin and a fluoroquinolones. Local treatment of the auditory canal
      including cleaning and application of antimicrobial agents was performed in all
      the cases. Surgical debridement of soft tissue and infected bone was performed in
      one patient who did not respond to medical management. Repeated scintigraphies
      with gallium were used to follow the course under treatment in only three cases.
      We had a 89.4% cure rate with only three cases of recurrence. We reviewed the
      data in the literature on necrotizing otitis externa and present the important
      diagnostic, imaging, and therapeutic aspects of the disease.

PMID- 20058155
TI  - Modeling progression in radiation-induced lung adenocarcinomas.
AB  - Quantitative multistage carcinogenesis models are used in radiobiology to
      estimate cancer risks and latency periods (time from exposure to clinical
      cancer). Steps such as initiation, promotion and transformation have been modeled
      in detail. However, progression, a later step during which malignant cells can
      develop into clinical symptomatic cancer, has often been approximated simply as a
      fixed lag time. This approach discounts important stochastic mechanisms in
      progression and evidence on the high prevalence of dormant tumors. Modeling
      progression more accurately is therefore important for risk assessment. Unlike
      models of earlier steps, progression models can readily utilize not only
      experimental and epidemiological data but also clinical data such as the results
      of modern screening and imaging. Here, a stochastic progression model is
      presented. We describe, with minimal parameterization: the initial growth or
      extinction of a malignant clone after formation of a malignant cell; the likely
      dormancy caused, for example, by nutrient and oxygen deprivation; and possible
      escape from dormancy resulting in a clinical cancer. It is shown, using cohort
      simulations with parameters appropriate for lung adenocarcinomas, that
      incorporating such processes can dramatically lengthen predicted latency periods.
      Such long latency periods together with data on timing of radiation-induced
      cancers suggest that radiation may influence progression itself.

PMID- 20058156
TI  - Predicting and manipulating the incidence of inattentional blindness.
AB  - Inattentional blindness (IB) occurs when an observer, who is engaged in a
      resource-consuming task, fails to notice an unexpected although salient stimulus
      appearing in their visual field. The incidence of IB is affected by changes in
      stimulus-driven properties, but little research has examined individual
      differences in IB propensity. We examine working memory capacity (WMC),
      processing styles (flicker task), inhibition (Stroop task), and training in
      predicting IB. WMC is associated with IB (Experiments 1 and 2) but neither
      processing style (Experiment 1) nor inhibition (Experiment 2) was associated. In
      Experiment 2, prior training on a task reduced the incidence of IB compared to no
      prior training, and this effect was significantly larger when trained on the same
      tracking task as that used in the IB task rather than a different task. We
      conclude that IB is related to WMC and that training can influence the incidence
      of IB.

PMID- 20058157
TI  - Changing climate in Hungary and trends in the annual number of heat stress days.
AB  - Global climate change can have serious direct effects on animal health and
      production through heat stress. In Hungary, the number of heat stress days per
      year (YNHD), i.e., days when the temperature humidity index (THI) is above a
      specific comfort threshold, has increased in recent years based on observed
      meteorological data. Between 1973 and 2008, the countrywide average increase in
      YNHD was 4.1% per year. Climate scenarios based on regional climate models (RCM)
      were used to predict possible changes in YNHD for the near future (2021-2050)
      relative to the reference period (1961-1990). This comparison shows that, in
      Hungary, the 30-year mean of YNHD is expected to increase by between 1 and 27
      days, depending on the RCM used. Half of the scenarios investigated in this study
      predicted that, in large parts of Hungary, YNHD will increase by at least 1 week.
      However, the increase observed in the past, and that predicted for the near
      future, is spatially heterogeneous, and areas that currently have large cattle
      populations are expected to be affected more severely than other regions.

PMID- 20058158
TI  - Circulating pro-inflammatory cytokines and adiponectin in young men with type 2
      diabetes.
AB  - This study was designed to investigate plasma circulating pro-inflammatory
      cytokines, adiponectin and high-sensitive C-reactive protein (hsCRP) in young men
      with type 2 diabetes. New-onset young men with type 2 diabetes (young diabetes,
      YDM; age between 10 and 25) were recruited and divided into a non-obese group
      (NOYDM, body mass index, BMI ? 25 kg/m(2), N = 23) and an obese group (OBYDM, BMI
      ? 25 kg/m(2), N = 24). Twenty-four non-obese non-diabetic young men served as
      controls. Hemoglobin A1c, fasting glycemic index, lipids, adiponectin, hsCRP,
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were determined.
      Insulin sensitivity and beta-cell function were calculated using the homeostasis
      model assessment method (HOMA-IR and HOMA-beta, respectively). Compared to
      controls, significantly greater HOMA-IR (7.9 +/- 1.9 and 10.4 +/- 2.5 vs. 1.5 +/-
      0.3, P < 0.001) and fasting insulin (103.3 +/- 21.1 and 209.9 +/- 24.4 vs. 48.5
      +/- 6.7 pmol/l, P < 0.01 and P < 0.001, respectively) were observed in NOYDM and
      OBYDM. There were significantly lower plasma adiponectin and higher hsCRP and TNF
      alpha levels in OBYDM, whereas higher TNF-alpha and IL-6 were shown in NOYDM.
      Spearman rank correlation analysis demonstrated significant correlations between
      BMI and adiponectin (R = -0.44, P < 0.005), CRP (R = 0.28, P < 0.05), TNF-alpha
      (R = 0.42, P < 0.005) and IL-6 (R = 0.33, P < 0.01) in all YDM. Among measured
      cytokines, only adiponectin was significantly correlated with HOMA-IR, this
      correlation was abolished when adjusted for age and BMI (R = -0.24, P = 0.12).
      YDM not only exhibits insulin resistance, but also has inflammatory and
      atherogenic properties. BMI might be a major determinant of those markers.

PMID- 20058159
TI  - Immunohistochemical analysis of inflammatory infiltrate in aggressive and chronic
      periodontitis: a comparative study.
AB  - This immunohistochemical study evaluated the inflammatory infiltrate with its
      cluster differentiation markers (CD 4, CD 8, CD 20, and CD 68) in aggressive and
      chronic periodontitis gingival tissues in order to identify the specific cell
      distribution. Twenty-seven human gingival biopsies were obtained and analyzed.
      Fourteen patients were suffering from chronic periodontitis and six from
      aggressive periodontitis; seven patients with healthy gingiva were included as
      the control group. The specimens were immunohistochemically stained for anti-CD 4
      (T helper cells), anti-CD 8 (T cytotoxic/suppressor), anti CD-20 (B plasma cells)
      and anti CD-68 (macrophages). Chronic periodontitis samples were mainly dominated
      by CD 4 and CD 8+ cells. On the contrary, in aggressive periodontitis patients
      all four cell types (CD 4, CD 8, CD 20 and CD 68 + cells, respectively) were
      remarkably increased. CD 20+ cells were significantly (p < 0.05) more prevalent
      in aggressive versus chronic periodontitis. The control samples expressed lower
      CD 4, CD 8, CD 20 and CD 68+ cells confirming a none inflammatory state. The
      present study demonstrates prevalence for CD 20+ cells in aggressive
      periodontitis lesions. However, further studies need to be performed to confirm
      and identify a clear pattern of inflammatory cells and hereafter the mechanisms
      sustaining the disease.

PMID- 20058160
TI  - Granulomatous transformation of capillary lesions in pulmonary-renal syndrome
      autologously induced anti-glomerular basement membrane disease in Wistar-Kyoto
      rats.
AB  - BACKGROUND: Pulmonary-renal syndrome is characterized by pulmonary hemorrhage and
      rapidly progressive glomerulonephritis in various immunological states.
      Histopathological analysis of pulmonary-renal syndrome is not yet complete.
      METHODS: Wistar-Kyoto (WKY) rats were sensitized using the noncollagenous (NC1)
      domain of type IV collagen from bovine kidney as an antigen. Histopathology of
      the kidneys and lungs was investigated with light microscopy,
      immunohistochemistry and electromicroscopy. Expression levels of cytokine mRNA
      were determined by real-time RT-PCR using renal tissue of rats. RESULTS:
      Macrophage-rich granulomatous glomerulonephritis and alveolar capillaritis
      accompanied with pulmonary hemorrhage were induced by the sensitization. The
      humoral antibody against NC1 was detected on the glomerular and alveolar
      capillary walls. Th2 cytokine IL-10 was dominant over Th1 cytokine IFN-gamma in
      renal tissues of WKY rats. CONCLUSION: The granulomatous transformation seemed to
      be induced by macrophage conspicuous capillaritis under dominant cellular immune
      reactions in WKY rats. In addition to Th1 cytokines, Th2 cytokines may also
      participate in the formation of granulomatous lesions.

PMID- 20058161
TI  - The methodology of neuroproteomics.
AB  - The human central nervous system (CNS) is the most complex organ in nature,
      composed of ten trillion cells forming complex neural networks using a
      quadrillion synaptic connections. Proteins, their modifications, and their
      interactions are integral to CNS function. The emerging field of neuroproteomics
      provides us with a wide-scope view of posttranslation protein dynamics within the
      CNS to better our understanding of its function, and more often, its dysfunction
      consequent to neurodegenerative disorders. This chapter reviews methodology
      employed in the neurosciences to study the neuroproteome in health and disease.
      The chapter layout parallels this volume's four parts. Part I focuses on modeling
      human neuropathology in animals as surrogate, accessible, and controllable
      platforms in our research. Part II discusses methodology used to focus analysis
      onto a subneuroproteome. Part III reviews analytical and bioinformatic
      technologies applied in neuroproteomics. Part IV discusses clinical
      neuroproteomics, from processing of human biofluids to translation in biomarkers
      research. Neuroproteomics continues to mature as a discipline, confronting the
      extreme complexity of the CNS proteome and its dynamics, and providing insight
      into the molecular mechanisms underlying how our nervous system works and how it
      is compromised by injury and disease.

PMID- 20058162
TI  - Modeling cerebral ischemia in neuroproteomics.
AB  - Protein changes induced by traumatic or ischemic brain injury can serve as
      diagnostic markers as well as therapeutic targets for neuroprotection. The focus
      of this chapter is to provide a representative overview of preclinical brain
      injury and proteomics analysis protocols for evaluation and discovery of novel
      biomarkers. Detailed surgical procedures have been provided for inducing MCAo and
      implantation of chronic indwelling cannulas for drug delivery. Sample collection
      and tissue processing techniques for collection of blood, CSF, and brain are also
      described including standard biochemical methodology for the proteomic analysis
      of these tissues.The dynamics of proteomic analysis is a multistep process
      comprising sample preparation, separation, quantification, and identification of
      proteins. Our approach is to separate proteins first by two-dimensional gel
      electrophoresis according to charge and molecular mass. Proteins are then
      fragmented and analyzed using matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF MS). Identification of proteins can be
      achieved by comparing the mass-to-charge data to protein sequences in respective
      databases.

PMID- 20058163
TI  - Clinical and model research of neurotrauma.
AB  - Modeling traumatic brain injury represents a major challenge for neuroscientists 
      to represent extremely complex pathobiological processes kept under close
      surveillance in the most complex organ of a laboratory animal. To ensure that
      such models also reflect those alterations evoked by and/or associated with
      traumatic brain injury (TBI) in man, well-defined, graded, simple injury
      paradigms should be used with clear endpoints that also enable us to assess the
      relevance of our findings to human observations. It is of particular importance
      that our endpoints should harbor clinical significance, and to this end,
      biological markers ultimately associated with the pathological processes operant
      in TBI are considered the best candidate. This chapter provides protocols for
      relevant experimental models of TBI and clinical materials for neuroproteomic
      analysis.

PMID- 20058164
TI  - Neuroproteomic methods in spinal cord injury.
AB  - Spinal cord injury (SCI) is a major public health problem with no known effective
      treatment. Traumatic injury to the spinal cord initiates a host of
      pathophysiological events that are secondary to the initial insult leading to
      neuronal dysfunction and death; yet, the molecular mechanisms underlying its
      dysfunction are poorly understood. Furthermore, while use of imaging methods
      (e.g., computed tomography scans and magnetic resonance imaging) may help define
      injury severity and location, they do not elucidate biological mechanisms of SCI
      progression. The lack of comparable biomarkers for monitoring SCI makes accurate
      diagnosis and evaluation of SCI progression difficult. Spinal cord contusion is
      an extensively used SCI model in rats that best represents the etiology of SCI in
      humans. In this chapter, we describe a two-dimensional (2D) gel electrophoresis
      based proteomic approach to investigate the injury-related differences in the
      proteome and phosphoproteome of spinal cord lesion epicenter at 24 h after spinal
      cord contusion in rats. The purpose of this study is to elucidate the mechanisms
      of acute spinal cord dysfunction, as well as discover novel biomarker candidates
      to evaluate the biological mechanisms of SCI progression and the injury severity.

PMID- 20058165
TI  - Modeling substance abuse for applications in proteomics.
AB  - The ability to model aspects of human addictive behaviors in laboratory animals
      provides an important avenue for gaining insight into the biochemical alterations
      associated with drug intake and the identification of targets for medication
      development to treat addictive disorders. The intravenous self-administration
      procedure provides the means to model the reinforcing effects of abused drugs and
      to correlate biochemical alterations with drug reinforcement. In this chapter, we
      provide a detailed methodology for rodent intravenous self-administration and the
      isolation and preparation of proteins from dissected brain regions for Western
      blot analysis and high-throughput proteomic analysis. Examples of cocaine-induced
      alterations in the abundances of ionotropic glutamate receptor subunits in
      reinforcement-related brain regions are provided.

PMID- 20058166
TI  - Protein aggregate characterization in models of neurodegenerative disease.
AB  - A pathological hallmark of many neurodegenerative diseases is the presence of
      protein aggregates. Transgenic mice that recapitulate this pathology are a
      valuable resource to isolate these proteins for detailed study. One aspect of our
      research program is to characterize and quantify aggregates beta-amyloid (Abeta)
      peptides, superoxide dismutase 1 (SOD1), and huntingtin (htt) that comprise
      pathologic lesions found in Alzheimer's disease, familial amyotrophic lateral
      sclerosis, and Huntington's disease, respectively. In this chapter, we describe
      methods, based on sequential detergent extraction and ultracentrifugation, to
      isolate and analyze these protein aggregates. These methods have been applied to
      human tissues to some extent, but have been highly useful in studies involving
      transgenic mouse models of these diseases.

PMID- 20058167
TI  - Sub-proteome processing: isolation of neuromelanin granules from the human brain.
AB  - The sub-proteome analysis of organelles is a field of high relevance for
      molecular biology, because it provides detailed insights into the protein
      composition of cellular compartments. This approach not only results in a
      catalogue of organellar proteins, but in fact holds the potential to uncover the
      enzymatic armament engaged in biochemical reactions and to identify novel
      mechanisms of organelle biogenic pathways. Knowledge about protein localization
      may be a first step towards extensive functional analyses of specific target
      proteins engaged in development, aging, or disease. Moreover, several disorders
      of the human brain include aberrant protein function in specific compartments.
      Thus, a closer look at cellular organelles will allow for advancing our current
      perceptions of pathogenic processes. This chapter aims to provide a
      methodological workflow given by the isolation of neuromelanin granules from the
      human midbrain. This approach encompasses several modular steps that can easily
      be adjusted to any other organelle of interest and follows the sequence of (1)
      organelle isolation, (2) isolation quality controls by transmission electron
      microscopy and Western immuno blotting, and (3) gel-based protein separation
      towards protein identification by mass spectrometry.

PMID- 20058168
TI  - Proteomic analysis of protein phosphorylation and ubiquitination in Alzheimer's
      disease.
AB  - Posttranslational modifications such as phosphorylation and ubiquitination serve,
      independently or together, as gatekeepers of protein transport and turnover in
      normal and disease physiologies. Aberrant protein phosphorylation is one of the
      defining pathological hallmarks of more than 20 different neurodegenerative
      disorders, including Alzheimer's disease (AD). The disruption of the
      phosphorylation of neurotransmitter receptors has been implicated as one of the
      causal factors of impaired memory function in AD (1-3). Another feature of AD is
      the aberrant accumulation of proteins that are normally degraded by the ubiquitin
      proteasome system upon being conjugated to ubiquitin. Thus, elucidating the
      protein targets of phosphorylation and ubiquitination that can serve as AD
      biomarkers will aid in the development of effective therapeutic approaches to the
      treatment of AD. This chapter provides details pertaining to the qualitative and
      quantitative liquid chromatography tandem mass spectrometry-based analysis of an
      affinity purified, phosphorylated, and ubiquitinated protein, paired-helical
      filament tau.

PMID- 20058169
TI  - Proteomics identification of carbonylated and HNE-bound brain proteins in
      Alzheimer's disease.
AB  - Free radicals and oxidative stress play a crucial role in the pathophysiology of
      a wide variety of diseases including cancer and neurodegenerative disorders.
      Reactive oxygen and reactive nitrogen species can react with biomolecules such as
      proteins, lipids, nucleic acid, etc. resulting in the formation of protein
      carbonyls, 3-nitrotyroine, HNE-bound proteins, etc. Such modifications in
      proteins often lead to functional impairment, and the identification of such
      oxidatively modified proteins may help in delineating the mechanism of disease
      1pathogenesis or progression.In this chapter, we described the protocol for the
      identification of oxidatively modified proteins, i.e., protein carbonyls and HNE
      bound proteins in a given biological sample using three important techniques,
      i.e., proteomics coupled with mass spectrometry and immunochemical detection.
      These methods are placed in the context of our studies on Alzheimer's disease.

PMID- 20058170
TI  - Mass spectrometric identification of in vivo nitrotyrosine sites in the human
      pituitary tumor proteome.
AB  - The chemically stable tyrosine nitration of a protein involves the addition of a
      nitro group (-NO(2)) to the phenolic ring of a tyrosine residue, which may be
      associated with nervous system physiological and pathological processes.
      Identification of nitrotyrosine sites on a protein could clarify the functional
      significance of the modification. Due to the rarity of nitrotyrosine sites in a
      proteome, tandem mass spectrometry, coupled with different techniques that
      isolate and enrich nitrotyrosine-containing proteins from a pituitary proteome,
      is currently the most effective method for site identification. Commercially
      available nitrotyrosine polyclonal/monoclonal antibodies enable one to detect
      nitrotyrosine-containing proteins in a two-dimensional gel electrophoresis (2DGE)
      map, and to preferentially enrich nitrotyrosine-containing proteins with
      immunoprecipitation. Our present protocols have integrated different
      isolation/enrichment techniques (2DGE; Western blots; nitrotyrosine
      immunoaffinity precipitation) and two different tandem mass spectrometry methods
      (MALDI-MS/MS; ESI-MS/MS) to determine the amino acid sequence of nitrotyrosine
      containing peptides that derive from nitrated proteins. Bioinformatics tools are
      then used to correlate nitrotyrosine sites with a functional domain/motif in
      order to understand the relationship between tyrosine nitration and the
      structural/functions of proteins.

PMID- 20058171
TI  - Improved enrichment and proteomic analysis of brain proteins with signaling
      function by heparin chromatography.
AB  - Detection of low-abundance proteins with signaling function is essential for the
      identification of biomarkers and novel drug targets. We present a protocol for
      specific enrichment of secreted proteins with signaling function by combining
      subcellular fractionation with heparin chromatography. The subcellular
      fractionation includes the preparation of a fraction enriched in cytosolic
      proteins. A further enrichment was achieved by heparin chromatography. The
      proteins eluted from the heparin column were analyzed by MudPIT tandem mass
      spectrometry and identified with the use of an in silico algorithm. Forty-eight
      percent of the identified proteins (188 out of 391) bound to the heparin matrix.
      Fifty-four percent of them (101) are secreted proteins with signaling function
      and 23% (44) of the enriched signaling proteins had not been detected by 2D PAGE
      without application of the heparin enrichment step. The heparin chromatography
      method can be combined with other proteomics enrichment approaches, such as ion
      exchange or reversed phase chromatography.

PMID- 20058172
TI  - Calmodulin-binding proteome in the brain.
AB  - Calcium dyshomeostasis is involved in neuropathological conditions such as
      traumatic brain injury (TBI), stroke, and neurodegenerative diseases. Under such
      conditions in the brain, calmodulin (CaM), a Ca(2+) sensor, mediates critical
      signaling functions through binding and regulating a diverse population of
      downstream targets referred to as calmodulin-binding proteins (CaMBPs). We
      developed a CaM-affinity capture method followed by reversed-phase liquid
      chromatography tandem mass spectrometry (RPLC-MSMS) to study the calcium
      dependent CaM-binding proteome in rat brain. A total of 69 potential CaMBPs were
      identified by this proteomic technique, of which 26 were known CaMBPs and 43 were
      putative novel CaMBPs. This study shows that the CaM-affinity capture when
      coupled with tandem mass spectrometry may serve as an effective tool toward
      constructing a brain CaM-binding proteomic network. The general methods described
      here can be applied to study possible alternations of calmodulin-binding proteome
      in neurological, neurodegenerative, and psychiatric disorders.

PMID- 20058173
TI  - Separation of the neuroproteome by ion exchange chromatography.
AB  - Ion exchange chromatography is a fractionation technique applicable to the
      separation of brain-derived proteins based on charge. Proteome complexity
      overwhelms analytical approaches, which is mitigated by fractioning samples into
      simpler solutions. In this chapter we will cover the design, optimization, and
      execution of an ion exchange experiment for the separation of a brain lysate.
      Furthermore, helpful tips and pitfall will be revealed to aid with potential
      problems that may arise. The discussed proteomic methodology is applicable to
      multidimensional separations ahead of bottom-up or top-down proteomic strategies
      for characterizing the neuroproteome.

PMID- 20058174
TI  - iTRAQ-based shotgun neuroproteomics.
AB  - Shotgun proteomics involves the analysis of peptides obtained by enzymatic
      digestions of proteins and subsequent identification via tandem mass
      spectrometry. This approach is an effective method for studying global protein
      expression in neuronal systems. The method described here is a quantitative
      shotgun neuroproteomics method using amine-specific isobaric tags for a relative
      and absolute quantitation (iTRAQ)-based workflow. We will provide the technical
      details for sample preparation, two-dimensional liquid chromatography, tandem
      mass spectrometry, database search, and statistical analysis to identify
      differentially expressed proteins. We will use a recent study on a rat model of
      multiple sclerosis, experimental autoimmune encephalomyelitis to illustrate the
      successful application of this method.

PMID- 20058175
TI  - Methods in drug abuse neuroproteomics: methamphetamine psychoproteome.
AB  - Methamphetamine (METH) is recognized as one of the most abused psychostimulants
      in the USA. METH is an illicit drug that is known to exert neurotoxic effects on
      both dopaminergic and serotonergic neural systems. Our laboratory has been
      studying the biochemical mechanisms underlying MDMA and METH-induced neurotoxic
      effects both in vivo and in vitro. Our substance abuse research focuses on the
      global alteration of cortical protein expression in rats treated with acute METH.
      Altered protein expression was identified using a multistep protein
      separation/proteomic platform. Differential changes of the selected proteins were
      further confirmed by quantitative immunoblotting. Our study identified 82
      differentially expressed proteins, 40 of which were downregulated and 42 of which
      were upregulated post acute METH treatment. Proteins that were shown to be
      downregulated included collapsin response mediator protein-2 (CRMP-2), superoxide
      dismutase 1 (SOD 1), and phosphatidylethanolamine-binding protein-1 (PEBP-1).
      Proteins that were shown to be upregulated included authophagy-linked microtubule
      associated protein light chain 3 (LC3), synapsin-1, and Parkinsonism-linked
      ubiquitin carboxy-terminal hydroxylase-L1 (UCH-L1). This differential protein
      expression highlights on the neurotoxic mechanism involved in METH exposure as
      well as to discover potential markers for METH-induced neurotoxicity. In this
      chapter, we describe the current protocols for the in vivo rat model of acute
      METH treatment (40 mg/kg) coupled with the description of the multistep
      separation platform applied. These methods and protocols are discussed in the
      paradigm of acute model of methamphetamine drug abuse and can be applied to other
      models of substance abuse such as to MDMA or cocaine.

PMID- 20058176
TI  - Shotgun protein identification and quantification by mass spectrometry in
      neuroproteomics.
AB  - Shotgun proteomics is based on identification and quantification of peptides from
      digested proteins using tandem mass spectrometry. In this chapter, we discuss
      computational methods to analyze tandem mass spectra of peptides, including
      database searching, de novo peptide sequencing, hybrid approaches, library
      searching, and unrestricted modification search. A special focus is given to
      database searching programs, since they are the most widely used. The process of
      inferring proteins from identified peptides is then discussed. We also provide
      description of key steps in the quantitative analysis of mass spectrometry
      proteomics data. These methods are valuable tools for discovery and hypothesis
      driven analyses in neuroproteomics.

PMID- 20058177
TI  - Identification of glycoproteins in human cerebrospinal fluid.
AB  - Human cerebrospinal fluid (CSF), which circulates within the ventricles of the
      brain and the subarachnoid space of the central nervous system (CNS), is an
      excellent source for proteomic discovery of biomarkers in neurodegenerative
      disorders, including Alzheimer's and Parkinson's disease. Protein glycosylation
      is an abundant and biologically significant posttranslational modification.
      Glycoproteins, commonly associated with membrane and secreted proteins, are
      highly enriched in body fluids, including CSF. Focusing on glycoproteins also
      improves the dynamic range of proteomic profiling of the CSF, where low abundance
      proteins are difficult to identify because of the CSF's enormous complexity. As
      an ongoing process to define the human CSF proteome, we have recently employed a
      complementary proteomic approach, with integrated lectin affinity column and
      hydrazide chemistry, for CSF glycoprotein identification. This investigation has
      revealed many proteins of low abundance that are related to the CNS structurally
      and/or functionally. This review centers on the technical details involved in
      various steps in sample preparation as well as proteomic analysis of CSF
      glycoproteins.

PMID- 20058178
TI  - Mass spectrometric analysis of body fluids for biomarker discovery.
AB  - Hinging on the concept that extracellular proteins and polypeptides will provide
      information on the physiological state of specific organs, or even entire
      organisms, proteomic analysis of biological fluids for biomarker discovery has
      seen rapid expansion in recent years. Although multiple studies have had success
      using mass spectrometric analytical techniques for determination of proteins
      within a sample, inspection of naturally occurring species has been difficult,
      with most analyses using bottom-up methodology. We have applied a new
      fragmentation method, electron transfer dissociation (ETD), to this problem. We
      have previously illustrated the benefits to spectral quality and total
      identifications when using a combination of the complementary fragmentation
      techniques, ETD, and collision-activated dissociation, for analysis of naturally
      occurring proteins and polypeptides within biological fluids.

PMID- 20058179
TI  - Traumatic brain injury biomarkers: from pipeline to diagnostic assay development.
AB  - In recent years, the term proteomics is often mentioned together with biomarker
      discovery, as proteomic studies have the capability of identifying unique and
      unobvious protein biomarkers from tissues or biofluids derived from animal models
      or human clinical samples inflicted with various diseases. Proteomics has yielded
      hundreds of potential biomarker candidates. However, biomarker discovery is only
      the beginning of a long road for generating a validated, clinically relevant, and
      FDA-approved biomarker assay. Many technical, financial, legal, and regulatory
      hurdles have to be overcome before the components can be commercially produced
      (1, 2). This chapter outlines in a condensed version the steps to successfully
      develop clinically acceptable biomarkers, given the marker of choice withstands
      the rigor of developmental challenges along the road.

PMID- 20058180
TI  - Translation of neurological biomarkers to clinically relevant platforms.
AB  - Like proteomics more generally, neuroproteomics has recently been linked to the
      discovery of biochemical markers of central nervous system (CNS) injury and
      disease. Although neuroproteomics has enjoyed considerable success in discovery
      of candidate biomarkers, there are a number of challenges facing investigators
      interested in developing clinically useful platforms to assess biomarkers for
      damage to the CNS. These challenges include intrinsic physiological complications
      such as the blood-brain barrier. Effective translation of biomarkers to clinical
      practice also requires development of entirely novel pathways and product
      development strategies. Drawing from lessons learned from applications of
      biomarkers to traumatic brain injury, this study outlines major elements of such
      a pathway. As with other indications, biomarkers can have three major areas of
      application: (1) drug development; (2) diagnosis and prognosis; (3) patient
      management. Translation of CNS biomarkers to practical clinical platforms raises
      a number of integrated elements. Biomarker discovery and initial selection needs
      to be integrated at the earliest stages with components that will allow
      systematic prioritization and triage of biomarker candidates. A number of
      important criteria need to be considered in selecting clinical biomarker
      candidates. Development of proof of concept assays and their optimization and
      validation represent an often overlooked feature of biomarker translational
      research. Initial assay optimization should confirm that assays can detect
      biomarkers in relevant clinical samples. Since access to human clinical samples
      is critical to identification of biomarkers relevant to injury and disease as
      well as for assay development, design of human clinical validation studies is an
      important component of translational biomarker research platforms. Although these
      clinical studies share much in common with clinical trials for assessment of drug
      therapeutic efficacy, there are a number of considerations unique to these
      efforts. Finally, platform selection and potential assay commercialization need
      to be considered. Decisions regarding whether or not to seek FDA approval also
      significantly influence translational research structures.

PMID- 20058181
TI  - Search for histamine H4 receptor ligands in the group of 4-methylpiperazino amide
      derivatives.

PMID- 20058182
TI  - Glycosylated quantum dots for the selective labelling of Kluyveromyces bulgaricus
      and Saccharomyces cerevisiae yeast strains.
AB  - Highly fluorescent CdTe quantum dots (QDs) stabilized by thioglycolic acid (TGA)
      were prepared by an aqueous solution approach and used as fluorescent labels in
      detecting yeast cells. Sugars (mannose, galactose or glucose) were adsorbed on
      CdTe@TGA QDs and the interaction of these nanoparticles with yeast cells was
      studied by fluorescence microscopy. Results obtained demonstrate that galactose
      and mannose functionalized QDs associate respectively with Kluyveromyces
      bulgaricus and Saccharomyces cerevisiae yeast strains due to saccharide/lectin
      specific recognition. Glucose-functionalized CdTe QDs, which are not recognized
      by cell lectins, preferentially localize in the bud scars of S. cerevisiae.

PMID- 20058184
TI  - Analysis of geographic and pairwise genetic distances among sheep populations.
AB  - This study assessed the usefulness of geographic and pairwise genetic distances
      in the characterization of five sheep populations using 15 microsatellite
      markers. The average F statistics across loci were F (IT) = 0.523 +/- 0.140, F
      (ST) = 0.363 +/- 0.131, and F (IS) = 0.263 +/- 0.092. The average heterozygosity
      was 0.716 +/- 0.069, polymorphism information content was 0.691 +/- 0.070, and
      effective number of alleles was 3.736 +/- 0.998. Sheep populations clustered into
      group 1 (Hu and Tong breeds) and group 2 (small-tailed Han, Wadi, and Tan
      breeds). Reynolds' distance varied from 0.0062 to 0.0499, and the range of gene
      flow (N (m)) was 4.8834-40.0726 among the sheep populations. The results showed
      that the genetic structure of the five populations was not consistent with their
      genetic distances, and the population genetic divergence was not linearly related
      to geographic distance as indicated by a Mantel test (P = 0.7936).

PMID- 20058183
TI  - A comparison of the efficacy of an appearance-focused skin cancer intervention
      within indoor tanner subgroups identified by latent profile analysis.
AB  - The reduction of intentional exposure to ultraviolet (UV) radiation is an
      important area of skin cancer prevention. Hillhouse et al. (Cancer 113:3257-3266,
      2008) have developed an appearance-focused intervention with evidence of efficacy
      in lowering indoor tanning UV exposure in young women. In the current study, a
      subgroup approach was used to determine moderators of intervention efficacy.
      Undergraduate females in two regions of the United States (n = 362) were
      randomized into an intervention or control condition. Latent profile analysis was
      used to identify subgroups of indoor tanners based on patterns of indoor tanning
      motives. Intervention efficacy was examined within each subgroup. We found
      evidence for 4 subgroups of tanners: knowledgeable-appearance tanners, low
      knowledge tanners, low-knowledge, relaxation tanners, and knowledgeable, low
      appearance and low-relaxation tanners. The intervention significantly reduced
      indoor tanning for the low-knowledge subgroup (34% of the sample). The utility of
      the subgroup approach in developing targeted behavioral skin cancer interventions
      is discussed.

PMID- 20058185
TI  - Effect of dietary marine lipids on female white bass ova compositions and progeny
      survival.
AB  - We evaluated white bass ovum fatty acid composition as well as embryonic and
      larval survival after varying n-3 and n-6 long-chain polyunsaturated fatty acid
      (LC-PUFA) concentrations in maternal diets. Diets containing graded levels (0,
      33, 66, or 100%) of squid to menhaden oils were fed daily to apparent satiation
      to female white bass for 8 weeks prior to spawning. Embryonic survival was
      negatively related to maternal squid oil intake (P=0.015, R2=0.970). Squid oil
      fed broodstock produced ova with decreased 20:5n-3 and increased C18
      polyunsaturated fatty acid concentrations, largely reflecting the fatty acid
      profile of squid oil. Within ovum phospholipid, accumulation of 18:2n-6 may have
      altered biological function resulting in the lower embryonic survival among ova
      produced from the squid oil-fed broodstock. Our data suggest the importance of
      feeding white bass broodstock diets high in total n-3 LC-PUFA (at least 4.0% dry
      matter), and 20:5n-3-rich lipid sources such as menhaden oil can be effectively
      utilized by female white bass to produce quality ova.

PMID- 20058186
TI  - Association of pre-transplant dialysis duration with outcome in kidney transplant
      recipients: a prevalent cohort study.
AB  - INTRODUCTION: Dialysis treatment prior to transplantation may contribute to
      premature mortality and graft loss in kidney-transplanted patients. In this
      prevalent cohort study (TransQol-HU Study), we analyzed the association between
      pre-transplant dialysis duration versus mortality and death-censored graft loss
      in kidney-transplanted patients. METHODS: Data from 926 kidney-transplanted
      patients followed at a single outpatient transplant center were analyzed. Socio
      demographic parameters, laboratory data, medical history, donor characteristics
      and information on co-morbidities were collected at baseline. Data on 5-year
      outcome (graft loss, mortality) were collected. RESULTS: In multivariate
      analyses, pre-transplant dialysis duration was an independent risk factor for
      mortality (HR(for each month increase) = 1.011; 95% CI: 1.005-1.016) and also for
      death-censored graft loss (HR(for each month increase) = 1.008; 95% CI: 1.001
      1.015) after adjustment for several co-variables. In the multivariate model,
      patients with less than 1 year (HR = 0.498; 95% CI: 0.302-0.820; P = 0.006) and 1
      3 years (HR = 0.577; 95% CI: 0.371-0.899; P = 0.015) of pre-transplant dialysis
      had significantly better survival after transplantation compared to those with
      more than 3 years on dialysis. CONCLUSIONS: These findings add further strength
      to existing evidence about the significant association between longer pre
      transplant dialysis duration and poor outcome in kidney-transplanted patients.

PMID- 20058187
TI  - Partitioned fluid-solid coupling for cardiovascular blood flow: left-ventricular
      fluid mechanics.
AB  - We present a 3D code-coupling approach which has been specialized towards
      cardiovascular blood flow. For the first time, the prescribed geometry movement
      of the cardiovascular flow model KaHMo (Karlsruhe Heart Model) has been replaced
      by a myocardial composite model. Deformation is driven by fluid forces and
      myocardial response, i.e., both its contractile and constitutive behavior.
      Whereas the arbitrary Lagrangian-Eulerian formulation (ALE) of the Navier-Stokes
      equations is discretized by finite volumes (FVM), the solid mechanical finite
      elasticity equations are discretized by a finite element (FEM) approach. Taking
      advantage of specialized numerical solution strategies for non-matching fluid and
      solid domain meshes, an iterative data-exchange guarantees the interface
      equilibrium of the underlying governing equations. The focus of this work is on
      left-ventricular fluid-structure interaction based on patient-specific magnetic
      resonance imaging datasets. Multi-physical phenomena are described by temporal
      visualization and characteristic FSI numbers. The results gained show flow
      patterns that are in good agreement with previous observations. A deeper
      understanding of cavity deformation, blood flow, and their vital interaction can
      help to improve surgical treatment and clinical therapy planning.

PMID- 20058189
TI  - Molecular cloning, characterization and expression of PmRsr1, a Ras-related gene
      from yeast form of Penicillium marneffei.
AB  - GTP-binding proteins such as Ras act as molecular switches in a large number of
      signal pathways. In this report, we isolated and characterized a novel Ras small
      monomeric GTPase Rsr1 gene, designated PmRsr1, from yeast-form Penicillium
      marneffei. The full-length PmRsr1 cDNA sequence is 1,866 bp in size, and contains
      an open reading frame of 642 bp encoding 213 amino acids. The predicted molecular
      mass of PmRsr1 is 24.41 kDa with an estimated theoretical isoelectric point of
      9.21. The deduced amino acid sequence of PmRsr1 shows 87% identity with that of
      Aspergillus fumigatus and A. clavatus. Eight exons and seven introns are
      identified within the 2,102 bp PmRsr1 genomic DNA sequence of P. marneffei. The
      open reading frame was subcloned into the pcDNA6-myc-His B expression vector, and
      the recombinant plasmid was transfected into Vero cell line. The expressed fusion
      protein was analyzed by SDS-PAGE and western blotting. Differential expression of
      the PmRsr1 was demonstrated by real-time RT-PCR. The expression of PmRsr1 was the
      highest in the yeast phase comparing with that in the mycelia and conidia phases.

PMID- 20058190
TI  - High level of Notch1 protein is associated with poor overall survival in
      colorectal cancer.
AB  - BACKGROUND: Notch1 regulates cell proliferation, development, and apoptosis.
      Aberrant expression of Notch1 has been discovered in many types of tumors. We
      examined Notch1 expression in colorectal cancer to assess its role as a
      prognostic indicator. METHODS: Notch1 protein expression was examined by
      immunohistochemistry in 223 surgically resected specimens of colorectal cancer
      and adjacent tissues. The relationship between various clinicopathological
      features and overall patient survival rate was analyzed. The association of
      Notch1 expression with the colorectal cancer survival rate was assessed by Kaplan
      Meier and Cox proportional-hazards regression. RESULTS: Significantly high Notch1
      expression was found in colorectal cancer cells compared with that of normal
      colorectal epithelial cells. Notch1 was positively correlated with depth of
      invasion (P = 0.005), lymph node metastases (P = 0.03), and tumor-node-metastasis
      (TNM) stage (P < 0.001). Consistently, the overall survival rate was
      significantly lower for patients with Notch1-positive than those with Notch1
      negative tumors. However, no correlation between Notch1 expression and patient
      age, sex or tumor location was found. CONCLUSION: Notch1 might serve as a novel
      prognostic marker that is independent of, and additive to, the TNM staging
      system.

PMID- 20058191
TI  - Endometrial carcinoma with extra-abdominal metastasis: improved prognosis
      following cytoreductive surgery.
AB  - BACKGROUND: Incidence of endometrial carcinoma, the most common malignancy of the
      female pelvis, has been steadily increasing during the last three decades. The
      prognosis for stage IVb cases with extra-abdominal metastases is extremely poor,
      with no current consensus regarding treatment. The aim of the present study was
      to examine the benefits of cytoreductive surgery for such cases. METHODS:
      Clinicopathological features of 33 stage IVb cases of endometrial carcinoma
      diagnosed during the 1991-2008 study period were retrospectively reviewed
      utilizing clinical records. Cytoreduction was conducted in 30 cases. RESULTS: The
      median progression-free survival (PFS) and overall survival (OS) of those
      patients with optimal cytoreduction of their disease (with residual masses < or
      =2 cm), were significantly better than those with suboptimal reduction (with
      residual masses > 2 cm), not only among the 15 stage IVb patients with only intra
      abdominal metastasis (group I) (P = 0.0003 and 0.0007) but also among the 15
      cases with extra-abdominal metastasis (group E) (P = 0.013 and 0.016).
      Multivariate Cox proportional-hazards analysis demonstrated that the adjusted
      hazard ratio (HR) for the maximum size of residual disease (>2 vs. < or =2 cm)
      was 10.4 [95% confidence interval (CI), 1.27-84.70, P = 0.030] in group I and
      16.92 (95% CI, 1.41-203.09, P = 0.026) in group E. CONCLUSIONS: This is the first
      demonstration that aggressive cytoreductive surgery for stage IVb endometrial
      carcinoma with extra-abdominal metastasis has a beneficial role. However, further
      investigation is still required to establish better standard therapy for stage
      IVb endometrial cancer.

PMID- 20058192
TI  - Advanced gastric cancer with early cancer macroscopic appearance: is it worthy of
      D2 lymphadenectomy?
AB  - BACKGROUND: Previous studies report that 5.9-22.2% of patients with
      preoperatively diagnosed early gastric cancers were eventually proven to have
      advanced gastric cancers by postoperative pathological examination. Such
      misdiagnosed cases commonly had cancers with macroscopic appearance like early
      gastric cancer and consequently can be recognized as a subgroup of cancer, namely
      advanced gastric cancer with early cancer macroscopic appearance (eAGC).
      Theoretically eAGCs might require D2 lymphadenectomy, but frequently undergo
      limited lymphadenectomy. However, the validity of the limited surgery is still
      unclear. METHODS: Clinicopathologic features of 134 patients with eAGC were
      retrospectively reviewed and compared with those of patients with early gastric
      cancers and advanced gastric cancers, respectively. RESULTS: Clinicopathologic
      features of eAGCs were similar to those of submucosa cancers, but significantly
      different from those of mucosa cancers and other muscularis propria cancers.
      Tumor size, lymphatic and/or blood vessels invasion (LBVI), and depth of invasion
      were identified as independent factors predicting lymph node metastasis; however,
      postoperative stage was not. All patients with eAGCs were proven to have lymph
      node metastasis restricted to the perigastric lymph nodes and lymph nodes at
      stations 7, 8a, and 9. Age, LBVI, and depth of invasion were independent
      prognostic factors for patients with preoperatively diagnosed early gastric
      cancers; however, the misdiagnosis of early cancer and the option of
      lymphadenectomy (D2 or not D2) had no impact on patient survival. The incidence
      of recurrence of eAGCs was similar to that of submucosa cancers, but
      significantly different from that of mucosa cancers and other muscularis propria
      cancers. CONCLUSIONS: Modified gastrectomy B (dissection of perigastric lymph
      nodes and nodes at stations 7, 8a, and 9) might be recommended for patients with
      eAGCs.

PMID- 20058193
TI  - Trends in patient cost sharing for clinical services used as quality indicators.
AB  - BACKGROUND: Patient copayments for all medical services have increased
      dramatically. There are few data available regarding how copayments have changed
      for services commonly considered to be quality indicators. OBJECTIVE: Describe
      the relative change in copayments for services used as quality indicators and
      interventions subject to programs to control utilization. DESIGN: A large claims
      database was used to assess copayment changes from 2001 to 2006 for selected drug
      and non-drug services in patient cohorts with specific chronic diseases.
      SUBJECTS: Approximately 5 million commercially-insured individuals enrolled in a
      variety of fee-for-service and capitated health plans. MEASUREMENTS: Copayment
      trends were calculated as the change in the average amount paid per unit service
      from 2001 to 2006. RESULTS: Out-of-pocket payments for services targeted by
      quality improvement initiatives increased substantially [>50%] and in a similar
      magnitude to interventions subject to programs to control their use. For
      prescription drugs, the trend was driven more by copayment increases for branded
      medications [$10 per prescription] than for generic drugs [$2 per prescription].
      Copayments for non-drug preventive services rose modestly. CONCLUSIONS: Benefit
      designers should consider reversing the trend of copayment increases for services
      considered to be indicators of high quality care.

PMID- 20058194
TI  - Study of the action of Se and Cu on the growth metabolism of Escherichia coli by
      microcalorimetry.
AB  - The biological effect of Se and Cu2(+) on Escherichia coli (E. coli) growth was
      studied by using a 3114/3236 TAM Air Isothermal Calorimeter, ampoule method, at
      37 degrees C. From the thermogenesis curves, the thermokinetic equations were
      established under different conditions. The kinetics showed that a low
      concentration of Se (1-10 MUg/mL) promoted the growth of E. coli, and a high
      concentration of Se (>10 MUg/mL) inhibited the growth, but the Cu2(+) was always
      inhibiting the growth of E. coli. Moreover, there was an antagonistic or positive
      synergistic effect of Se and Cu2(+) on E. coli in the different culture medium
      when Se was 1-10 MUg/ml and Cu2(+) was 1-20 MUg/ml. There was a negative
      synergistic effect of Se and Cu2(+) on E. coli when Se was higher than 10 MUg/ml
      and Cu2(+) was higher than 20 MUg/ml. The antagonistic or synergistic effect
      between Se and Cu2(+) on E. coli was related to the formation of Cu-Se complexes
      under the different experimental conditions chosen.

PMID- 20058195
TI  - The practical consequences of a national human embryonic stem cell registry.
AB  - The executive order and issuance of federal guidelines for human embryonic stem
      cell research are positive developments and will produce long-term benefits by
      creating a new registry for hESC lines. But there may be short-term costs caused
      by regulatory uncertainty, procedural delay, and knock-on effects as national
      policies are adopted at state and local jurisdictions. Policymakers must ensure
      that national mechanisms of oversight for a new hESC registry are adequately
      funded, properly organized, transparent, and free of bureaucratic detail.

PMID- 20058196
TI  - Building a framework for embryonic microenvironments and cancer stem cells.
AB  - The putative existence of a cancer stem cell niche consisting of bi-directional
      stromal and stem cell secreting factors that trigger cancer stem cell growth and
      proliferation has been hypothesized in the nervous and hematopoietic systems. In
      light of this theory, it has been proposed that embryonic stem cell
      microenvironments, upon interactions with cancer stem cells, may reprogram cancer
      cells resulting in a substantial inhibition of tumor cell properties. Here, we
      discuss emerging data that support this novel concept of cancer inhibitory
      factors produced in the context of embryonic microenvironments as well as by
      embryonic stem cells (ESCs).

PMID- 20058197
TI  - Insights into the regulation of a common variant of HMGA2 associated with human
      height during embryonic development.
AB  - Early genetic studies in the mouse and chicken identified the HMGA oncogene as a
      candidate that regulates body height. Subsequent genome-wide SNP studies revealed
      a significant association of rs1042725 genotypes CT and CC in the 3' UTR of HMGA2
      with human height. Together, these studies indicated that HMGA2 expression levels
      during prenatal development might be a critical factor that contributes to the
      height phenotype. In the present study, we sought to gain insight into the
      regulation of HMGA2 during human embryonic development and provide evidence that
      the rs1042725 genotype is unlikely to affect HMGA2 levels in pluripotent human
      embryonic stem cells (hESCs). This implies that hESCs in the inner cell mass of
      blastocysts are most likely not involved in determining the human height
      phenotype associated with this SNP. By applying a computational approach and cell
      based reporter assays, we then identified miR-196b as a candidate microRNA that
      could contribute to SNP-specific expression of HMGA2 during human prenatal
      development. We briefly discuss this result in the context of other known
      functions for miR-196b during vertebrate development.

PMID- 20058198
TI  - Developments and challenges in human embryonic stem cell research in Spain.
AB  - After years of following the trail of others, Spain is finally making a serious
      bid in science, specifically in regenerative medicine. In the framework of the
      European Union, Spain is setting up the basis for a solid collaborative network
      between public and private institutions, involving basic, translational, applied,
      technological and clinical researchers. In a society characterised by the idiom
      "slow but secure", it is still too soon to see the results of the huge economic
      and infrastructure investment made. We present here an overview of the challenges
      that have been surmounted and the ones that will have to be solved in order to
      situate Spain as a reference country in regenerative medicine worldwide.

PMID- 20058199
TI  - Cell lines derived from human parthenogenetic embryos can display aberrant
      centriole distribution and altered expression levels of mitotic spindle check
      point transcripts.
AB  - Human parthenogenetic embryos have recently been proposed as an alternative, less
      controversial source of embryonic stem cell (ESC) lines; however many aspects
      related to the biology of parthenogenetic embryos and parthenogenetic derived
      cell lines still need to be elucidated. We present here results on human cell
      lines (HP1 and HP3) derived from blastocysts obtained by oocyte parthenogenetic
      activation. Cell lines showed typical ESC morphology, expressed Oct-4, Nanog, Sox
      2, Rex-1, alkaline phosphatase, SSEA-4, TRA 1-81 and had high telomerase
      activity. Expression of genes specific for different embryonic germ layers was
      detected from HP cells differentiated upon embryoid body (EBs) formation.
      Furthermore, when cultured in appropriate conditions, HP cell lines were able to
      differentiate into mature cell types of the neural and hematopoietic lineages.
      However, the injection of undifferentiated HP cells in immunodeficient mice
      resulted either in poor differentiation or in tumour formation with the
      morphological characteristics of myofibrosarcomas. Further analysis of HP cells
      indicated aberrant levels of molecules related to spindle formation as well as
      the presence of an abnormal number of centrioles and autophagic activity. Our
      results confirm and extend the notion that human parthenogenetic stem cells can
      be derived and can differentiate in mature cell types, but also highlight the
      possibility that, alteration of the proliferation mechanisms may occur in these
      cells, suggesting great caution if a therapeutic use of this kind of stem cells
      is considered.

PMID- 20058201
TI  - Embryonic stem cell marker expression pattern in human mesenchymal stem cells
      derived from bone marrow, adipose tissue, heart and dermis.
AB  - Mesenchymal stem cells (MSCs) have been isolated from a variety of human tissues,
      e.g., bone marrow, adipose tissue, dermis, hair follicles, heart, liver, spleen,
      dental pulp. Due to their immunomodulatory and regenerative potential MSCs have
      shown promising results in preclinical and clinical studies for a variety of
      conditions, such as graft versus host disease (GvHD), Crohn's disease,
      osteogenesis imperfecta, cartilage damage and myocardial infarction. MSC cultures
      are composed of heterogeneous cell populations. Complications in defining MSC
      arise from the fact that different laboratories have employed different tissue
      sources, extraction, and cultivation methods. Although cell-surface antigens of
      MSCs have been extensively explored, there is no conclusive evidence that unique
      stem cells markers are associated with these adult cells. Therefore the aim of
      this study was to examine expression of embryonic stem cell markers Oct4, Nanog,
      SOX2, alkaline phosphatase and SSEA-4 in adult mesenchymal stem cell populations
      derived from bone marrow, adipose tissue, dermis and heart. Furthermore, we
      tested whether human mesenchymal stem cells preserve tissue-specific differences
      under in vitro culture conditions. We found that bone marrow MSCs express
      embryonic stem cell markers Oct4, Nanog, alkaline phosphatase and SSEA-4, adipose
      tissue and dermis MSCs express Oct4, Nanog, SOX2, alkaline phosphatase and SSEA
      4, whereas heart MSCs express Oct4, Nanog, SOX2 and SSEA-4. Our results also
      indicate that human adult mesenchymal stem cells preserve tissue-specific
      differences under in vitro culture conditions during early passages, as shown by
      distinct germ layer and embryonic stem cell marker expression patterns. Studies
      are now needed to determine the functional role of embryonic stem cell markers
      Oct4, Nanog and SOX2 in adult human MSCs.

PMID- 20058200
TI  - Isolation and differentiation of chondrocytic cells derived from human embryonic
      stem cells using dlk1/FA1 as a novel surface marker.
AB  - Few surface markers are available to monitor lineage differentiation during
      chondrogenesis. Recently, delta-like1/fetal antigen1 (dlk1/FA1), a transmembrane
      protein of the Notch/Delta/Serrata family, was shown to be essential for inducing
      early chondrogenesis. Thus, we investigated the possible use of dlk1/FA1 as a
      novel surface marker for chondroprogenitor cells during hESC differentiation. We
      found that, Dlk1/FA1 is expressed specifically in cells undergoing transition
      from proliferating to prehypertrophic chondrocytes during endochondral
      ossification of the mouse limb. In hESC cells, dlk1/FA1 was not expressed by
      undifferentiated hESC, but expressed during in vitro embryoid bodies (hEBs)
      formation upon down-regulation of undifferentiated markers e.g. Oct 3/4.
      Similarly, dlk1/FA1 was expressed in chondrocytic cells during in vivo teratoma
      formation. Interestingly, treatment of hEBs with Activin B, a member of TGF-ss
      family, markedly increased Dlk1 expression in association with up-regulation of
      the mesoderm-specific markers (e.g. FOXF1, KDR and VE-cadherin) and SOX9.
      dlk1/FA1(+) cells isolated by fluorescence activated cell sorting (FACS) were
      capable of differentiating into chondrocytic cells when cultured as micromass
      pellets in a xeno-free system containing TGFbeta1. In conclusion, we identified
      dlk1/FA1 as a novel marker of chondroprogenitor cells that undergo embryonic
      lineage progression from proliferation to the prehypertrophic stage. Tracking
      dlk1/FA1 expression as a mesoderm/chondroprogenitor surface marker provides a
      novel strategy for designing clinically relevant protocols to direct the
      differentiation of hESC into chondrocytes.

PMID- 20058202
TI  - Gene expression profile of mesenchymal stem cells from paired umbilical cord
      units: cord is different from blood.
AB  - Mesenchymal stem cells (MSC) are multipotent cells which can be obtained from
      several adult and fetal tissues including human umbilical cord units. We have
      recently shown that umbilical cord tissue (UC) is richer in MSC than umbilical
      cord blood (UCB) but their origin and characteristics in blood as compared to the
      cord remains unknown. Here we compared, for the first time, the exonic protein
      coding and intronic noncoding RNA (ncRNA) expression profiles of MSC from match
      paired UC and UCB samples, harvested from the same donors, processed
      simultaneously and under the same culture conditions. The patterns of intronic
      ncRNA expression in MSC from UC and UCB paired units were highly similar,
      indicative of their common donor origin. The respective exonic protein-coding
      transcript expression profiles, however, were significantly different.
      Hierarchical clustering based on protein-coding expression similarities grouped
      MSC according to their tissue location rather than original donor. Genes related
      to systems development, osteogenesis and immune system were expressed at higher
      levels in UCB, whereas genes related to cell adhesion, morphogenesis, secretion,
      angiogenesis and neurogenesis were more expressed in UC cells. These molecular
      differences verified in tissue-specific MSC gene expression may reflect
      functional activities influenced by distinct niches and should be considered when
      developing clinical protocols involving MSC from different sources. In addition,
      these findings reinforce our previous suggestion on the importance of banking the
      whole umbilical cord unit for research or future therapeutic use.

PMID- 20058203
TI  - A three dimensional anchorage independent in vitro system for the prolonged
      growth of embryoid bodies to study cancer cell behaviour and anticancer agents.
AB  - We describe a three dimensional (3D) anchorage independent in vitro protocol for
      the prolonged growth of human embryoid bodies (EBs) up to 90 days. We grew hESCs
      (46XX) in methylcellulose (MC) in motion culture in the presence of EB medium
      (EB), EB medium with Matrigel (EB + MAT), bulk culture medium (BCM), and BCM
      medium with Matrigel (BCM + MAT). All four experimental groups produced embryoid
      bodies (EBs) which with prolonged growth to 90 days acquired blood vessels and
      tissues from all three germ layers. Based on histology, microarray gene
      expression profiles and the definition for experimental teratomas, we could
      classify the EBs into early EBs, mature EBs and teratomas. The EB + MAT group
      produced the highest number of teratomas and their microarray data suggested the
      presence of inductive microenvironment niches and activation of pathways for self
      organization, morphogenesis and growth. When we microinjected hepatocarcinoma
      Green Fluorescent Protein cells (HepG2-GFP) (46XY) into the teratomas, after 10
      days the HepG2-GFP cells had grown inside the teratoma as confirmed by confocal
      microscopy and SRY gene analysis. This 3D-MC-(EB + MAT) in vitro system requires
      few cells to produce many teratomas, can be used to test pluripotency of
      potential human embryonic and induced pluripotent stem cell lines (hESC, hiPSC),
      and is an experimental humanized platform to study cancer cell behavior.

PMID- 20058204
TI  - A novel stem cell tag-less sorting method.
AB  - Growing interest in stem cell research has led to the development of a number of
      new methods for isolation. The lack of homogeneity in stem cell preparation blurs
      standardization, which however is recommended for successful applications. Among
      stem cells, mesenchymal stem cells (MSCs) are promising candidates for cell
      therapy applications. This paper presents a fractionation protocol based on a tag
      less, flow-assisted method of purifying, distinguishing and sorting MSCs. The
      protocol entails a suspension of cells in a transport fluid being injected into a
      ribbon-like capillary device by continuous flow. In a relatively short time
      (about 30 min) sorted cells are collected. The protocol has been applied to the
      improvement of MSC isolation, with a specific view to reducing cell manipulation
      operations, keeping instrumental simplicity and increasing analytical information
      for cell characterization. Applications such as MSC purification from epithelial
      contaminants, MSC characterization from various human sources and sorting of MSC
      subpopulations with high differentiation potential are described. The low cost,
      full biocompatibility and scale-up potential of the protocol presented could make
      the procedure attractive for stem cell selection.

PMID- 20058205
TI  - The use of discontinuous density gradients in stem cell research and application.
AB  - Discontinuous density gradients have been shown to be very efficient in sperm
      enrichment in assisted reproductive technologies (ART). Percoll
      [polyvinylpyrrolidone (PVP)-coated silica] which is a colloidal agent commonly
      used in such gradients is now confined to only research purposes in ART because
      its PVP component was considered toxic for clinical applications. The PVP
      component was replaced with silane instead and silane-coated colloidal silica
      marketed as Puresperm is currently being used for clinical sperm enhancement
      procedures in ART. The efficiency of these two agents has not been tested for
      human embryonic stem cell (hESC) and cancer cell research and clinical
      application. Herein we describe discontinuous density gradient protocols using
      PureSperm and Percoll for the separation and enrichment of hESCs and
      hepatocarcinoma cells from a mixed cell population. Trypan blue cell viability
      and CellTracker green cell counts are used to accurately quantify the extent of
      cell separation. We show that Puresperm provides good cell separation and
      enrichment with higher viable cell counts and greater number of fractions
      compared to Percoll. PureSperm being superior and safer compared to Percoll would
      be a better alternative for cell separation and enrichment in stem and cancer
      cell research and clinical applications.

PMID- 20058207
TI  - Bone marrow derived pluripotent cells are pericytes which contribute to
      vascularization.
AB  - Pericytes are essential to vascularization, but the purification and
      characterization of pericytes remain unclear. Smooth muscle actin alpha (alpha
      SMA) is one marker [corrected] of pericytes. The aim of this study is to purify
      the alpha-SMA positive cells from bone marrow and study the characteristics of
      these cells and the interaction between alpha-SMA positive cells and endothelial
      cells. The bone marrow stromal cells were harvested from alpha-SMA-GFP transgenic
      mice, and the alpha-SMA-GFP positive cells were sorted by FACS. The proliferative
      characteristics and multilineage differentiation ability of the alpha-SMA-GFP
      positive cells were tested. A 3-D culture model was then applied to test their
      vascularization by loading alpha-SMA-GFP positive cells and endothelial cells on
      collagen-fibronectin gel. Results demonstrated that bone marrow stromal cells are
      mostly alpha-SMA-GFP positive cells which are pluripotent, and these cells
      expressed alpha-SMA during differentiation. The alpha-SMA-GFP positive cells
      could stimulate the endothelial cells to form tube-like structures and
      subsequently robust vascular networks in 3-D culture. In conclusion, the bone
      marrow derived pluripotent cells include [corrected] pericytes and can contribute
      to vascularization.

PMID- 20058208
TI  - Thrombotic thrombocytopenic purpura: recognition and management.
AB  - Thrombotic thrombocytopenic purpura is a life-threatening multisystem disorder
      that represents both a diagnostic and a management challenge to clinicians. Early
      recognition of the condition coupled with rapid institution of plasma exchange
      has led to a dramatic improvement in prognosis. Studies performed over the past
      decade have elucidated the predominant pathophysiology, stemming from a
      deficiency of ADAMTS13, that accounts for the widespread microvascular deposition
      of platelet-von Willebrand factor in many sites, including the brain, kidney, and
      mesenteric vessels. However, in light of the mortality rate of 10-20%, much work
      remains to be done to translate advances in our understanding of pathophysiology
      into clinical practice. Improvements in medical management using
      immunosuppressive and other drugs are being actively explored in clinical trials.
      Agents that target ADAMTS13 autoantibody production by B-cells, such as anti-CD20
      monoclonal antibodies, have the potential to shorten the duration of plasma
      exchange treatment, reduce relapses, and transform the management of this once
      enigmatic disorder.

PMID- 20058213
TI  - [The deltopectoral flap for reconstruction of the tracheostoma and of the ventral
      neck region].

PMID- 20058210
TI  - Clusterin expression inversely correlates with chemosensitivity and predicts poor
      survival in patients with locally advanced cervical cancer treated with cisplatin
      based neoadjuvant chemotherapy and radical hysterectomy.
AB  - Overexpression of clusterin, an antiapoptotic molecule, has been reported to
      induce resistance to chemotherapy in a variety of cancer cell types. The aim of
      this study was to evaluate the significance of clusterin expression to predict
      response to platinum-based neoadjuvant chemotherapy and survival of patients with
      invasive cervical cancer who subsequently underwent radical hysterectomy. Biopsy
      specimens of invasive cervical cancer before neoadjuvant chemotherapy were
      obtained from 46 patients who subsequently underwent radical hysterectomy at
      Hokkaido University Hospital and Gunma University Hospital from 1994 to 2007. The
      expression of clusterin protein was analyzed by immunohistochemistry. Findings
      were evaluated in relation to several clinicopathological factors. Survival
      analyses were performed by the Kaplan-Meier curves and the log-rank test.
      Independent prognostic factors were determined by multivariate Cox regression
      analysis. Clusterin protein was mainly present in the cytoplasm of cervical
      cancer cells. The expression of clusterin protein in cervical cancer tissues
      before neoadjuvant chemotherapy was significantly related to poor response to
      chemotherapy among factors analyzed. Univariate analysis on prognostic factors
      showed that response to chemotherapy (p = 0.01), lymph node metastasis (p =
      0.02), and clusterin expression (p = 0.02) were related to survival. Multivariate
      analysis revealed that lymph node metastasis (p = 0.03), and clusterin expression
      (p = 0.03) were independent prognostic factors for survival of cervical cancer
      patients. We conclude that clusterin expression could be a new molecular marker
      to predict response to platinum-based chemotherapy and survival of patients with
      cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy.

PMID- 20058209
TI  - Pathophysiology of thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a disorder with characteristic von
      Willebrand factor (VWF)-rich microthrombi affecting the arterioles and
      capillaries of multiple organs. The disorder frequently leads to early death
      unless the patients are treated with plasma exchange or infusion. Studies in the
      last decade have provided ample evidence to support that TTP is caused by
      deficiency of a plasma metalloprotease, ADAMTS13. When exposed to high shear
      stress in the microcirculation, VWF and platelets are prone to form aggregates.
      This propensity of VWF and platelet to form microvascular thrombosis is mitigated
      by ADAMTS13, which cleaves VWF before it is activated by shear stress to cause
      platelet aggregation in the circulation. Deficiency of ADAMTS13, due to
      autoimmune inhibitors in patients with acquired TTP and mutations of the ADAMTS13
      gene in hereditary cases, leads to VWF-platelet aggregation and microvascular
      thrombosis of TTP. In this review, we discuss the current knowledge on the
      pathogenesis, diagnosis and management of TTP, address the ongoing controversies,
      and indicate the directions of future investigations.

PMID- 20058214
TI  - [Rhinoplasty: indication and planning].
AB  - A plethora of publications addresses surgical techniques in rhinoplasty, whereas
      substantially less has been published on psychological aspects and the planning
      of the procedure. This review covers the psychology of the rhinoplasty patient,
      risk factors for postoperative dissatisfaction, the surgeon-patient relationship,
      planning of the procedure using computer imaging and obtaining informed consent.

PMID- 20058216
TI  - [From the expert office: pseudo-"air-bone-gap" in sensorineural hearing loss].

PMID- 20058217
TI  - [Human papilloma virus in head and neck cancer].
AB  - Human papilloma viruses (HPV) may cause head and neck squamous cell carcinomas.
      HPV associated carcinomas mostly occur in the oropharynx and particularly in the
      palatine tonsil and base of tongue. Carcinomas at other sites are infrequently
      caused by HPV. The viral proteins E6 and E7 are crucial for malignant
      transformation. They functionally interfere with cellular proteins maintaining
      genomic integrity such as p53 and cell cycle control such as retinoblastoma
      protein. However, unlike carcinogens such as tobacco smoke, the virus does not
      disrupt the coding genes. Reliable HPV detection methods in histological
      specimens include in situ hybridisation of high risk DNA and immunohistochemical
      detection of p16. HPV positivity does not proof a causal relation between HPV and
      tumour. High risk HPV are also detectable in 10-20% of normal mucosal specimens.
      Irrespective of the various modalities available for treatment, HPV associated
      head and neck cancers have a better prognosis than their carcinogen caused
      counterparts. HPV positivity does not object to surgical treatment.

PMID- 20058220
TI  - Molecular Nutrition & Food Research - the journal's impact after 5 years.

PMID- 20058222
TI  - Characterization of CGRP protein expression in "satellite-like" cells and
      dendritic arbours of the mouse olfactory bulb.
AB  - The main olfactory bulb (OB) is made up of several concentric layers, forming
      circuitries often involving dendro-dendritic synapses. Important interactions
      between OB neurons occur in the external plexiform layer (EPL), where dendrites
      of tufted and Van Gehuchten cells form synapses with dendrites of deeper lying
      mitral, tufted, and granule cells. OB neurons display a variety of
      neurotransmitters. Here, the focus is on calcitonin gene-related peptide (CGRP),
      a 37-amino acid neuropeptide transmitter that is widely distributed in the
      central and peripheral nervous system. In the OB, CGRP-immunoreactive (ir) cell
      bodies were mostly observed in the mitral cell layer (MCL) of normal mice, and
      their number increased following colchicine treatment. Sparsely distributed CGRP
      ir cell bodies were also found in the EPL and granular cell layer. Double
      immunofluorescence experiments revealed a lack of co-localization between CGRP
      like immunoreactivity (LI) and corticotropin-releasing factor- or galanin-LI, two
      markers for mitral cells, and no CGRP-LI was found in cholecystokinin-,
      parvalbumin-, or vasoactive intestinal polypeptide-ir tufted/Van Gehuchten cells.
      CGRP-ir cell bodies were not found to co-localize glutamic acid decarboxylase 67
      (GAD67)-green fluorescence protein, gamma-aminobutyric acid (GABA)-, or
      calretinin-LI, although the possibility remains that CGRP-ir cells may contain
      low levels of GABA and/or GAD67 not detected by our methodology. Dendrites of
      CGRP-ir cells extensively ramified deep in the EPL and double-immunofluorescence
      revealed them to be adjacent with, often apparently contacting, dendrites of
      granule, mitral, tufted, and Van Gehuchten cells. We propose that these CGRP-ir
      cell bodies in the mouse OB are "satellite-like" cells within and, occasionally,
      close to the MCL.

PMID- 20058223
TI  - Near-peer role modeling: the fledgling scholars education paradigm.
AB  - Peer-assisted learning as de rigueur is reverberating in medical institutions
      around the world. Anatomy classroom activities are challenging and different, and
      the stressful environment of dissection rooms poses a greater challenge than what
      can be addressed through peer-assisted learning. It is here that "near-peer role
      modeling" is not only likely to be more useful, both to the students as well as
      their near-peer teachers, but also holds the answer to the worsening faculty
      shortage in anatomy education.

PMID- 20058221
TI  - Dopamine receptors in a songbird brain.
AB  - Dopamine is a key neuromodulatory transmitter in the brain. It acts through
      dopamine receptors to affect changes in neural activity, gene expression, and
      behavior. In songbirds, dopamine is released into the striatal song nucleus Area
      X, and the levels depend on social contexts of undirected and directed singing.
      This differential release is associated with differential expression of activity
      dependent genes, such as egr1 (avian zenk), which in mammalian brain are
      modulated by dopamine receptors. Here we cloned from zebra finch brain cDNAs of
      all avian dopamine receptors: the D1 (D1A, D1B, D1D) and D2 (D2, D3, D4)
      families. Comparative sequence analyses of predicted proteins revealed expected
      phylogenetic relationships, in which the D1 family exists as single exon and the
      D2 family exists as spliced exon genes. In both zebra finch and chicken, the D1A,
      D1B, and D2 receptors were highly expressed in the striatum, the D1D and D3
      throughout the pallium and within the mesopallium, respectively, and the D4
      mainly in the cerebellum. Furthermore, within the zebra finch, all receptors,
      except for D4, showed differential expression in song nuclei relative to the
      surrounding regions and developmentally regulated expression that decreased for
      most receptors during the sensory acquisition and sensorimotor phases of song
      learning. Within Area X, half of the cells expressed both D1A and D2 receptors,
      and a higher proportion of the D1A-only-containing neurons expressed egr1 during
      undirected but not during directed singing. Our findings are consistent with
      hypotheses that dopamine receptors may be involved in song development and social
      context-dependent behaviors.

PMID- 20058224
TI  - The gross anatomy course: an analysis of its importance.
AB  - The gross anatomy dissection course is a cost-intensive piece of undergraduate
      medical education that students and professionals alike describe as very
      important within the overall medical curriculum. We sought to understand more
      explicitly students' valuation of gross anatomy as an "important" course and so
      developed a quantitative longitudinal questionnaire. Medical students (n = 124)
      enrolled in the winter term 2006/2007 gross anatomy course at the Ulm University
      Faculty of Medicine were surveyed anonymously prior to, in the middle of, and at
      the end of the dissection course. Subgroups of students expressing rising or
      falling opinions of course value were identified and correlated with student
      opinions about the course's ability to convey professional competencies. Five
      point Likert scales were used for each survey item, which included such
      standardized instruments as the NeoFFI, BSI, and FBM. The study confirmed that
      medical students believe dissection to be valuable. Students indicated that
      participation in the course facilitated acquisition of anatomy knowledge as well
      as skills related to teamwork, coping with stress, and, to a lesser extent, time
      management. Students also noted that they developed less empathy than expected
      beforehand. Significant subgroup differences were observed relative to the
      competencies of teamwork, stress coping strategies, and empathy, as well as in
      students' stress levels associated with having to take a dissection course. Our
      study builds on previous work that has shown dissection courses help students
      develop professional competencies. The increase in professionalism might be a
      reason for the generally high value students place on the gross anatomy
      dissection course.

PMID- 20058225
TI  - Expression of calcium-binding proteins and nNOS in the human vestibular and
      precerebellar brainstem.
AB  - Information about the position and movement of the head in space is coded by
      vestibular receptors and relayed to four nuclei that comprise the vestibular
      nuclear complex (VNC). Many additional brainstem nuclei are involved in the
      processing of vestibular information, receiving signals either directly from the
      eighth nerve or indirectly via projections from the VNC. In cats, squirrel
      monkeys, and macaque monkeys, we found neurochemically defined subdivisions
      within the medial vestibular nucleus (MVe) and within the functionally related
      nucleus prepositus hypoglossi (PrH). In humans, different studies disagree about
      the borders, sizes, and possible subdivisions of the vestibular brainstem. In an
      attempt to clarify this organization, we have begun an analysis of the
      neurochemical characteristics of the human using brains from the Witelson Normal
      Brain Collection and standard techniques for antigen retrieval and
      immunohistochemistry. Using antibodies to calbindin, calretinin, parvalbumin, and
      nitric oxide synthase, we find neurochemically defined subdivisions within the
      MVe similar to the subdivisions described in cats and monkeys. The neurochemical
      organization of PrH is different. We also find unique neurochemical profiles for
      several structures that suggest reclassification of nuclei. These data suggest
      both quantitative and qualitative differences among cats, monkeys, and humans in
      the organization of the vestibular brainstem. These results have important
      implications for the analysis of changes in that organization subsequent to
      aging, disease, or loss of input.

PMID- 20058226
TI  - Polymer dynamics in torsion space.
AB  - The large scale motion of proteins, or covalently bonded polymers in general, is
      governed by the dynamics of the torsion angles, with bond lengths and bond angles
      kept approximately constant. In the present work, the Lagrangian equations of
      torsion motion are derived for a general macromolecule. The dynamics is
      implemented numerically for a test protein, using the velocity Verlet method as
      the integrator. The results indicate time steps of up to about 30 fs can be used
      for short time (up to at least 20 ps) simulations, before the dynamics and energy
      start to differ significantly from results obtained with smaller time steps. For
      longer time simulations, up to 1000 ps, a time step of 10 fs is relatively safe.

PMID- 20058227
TI  - Ab initio periodic study of the conformational behavior of glycine helical
      homopeptides.
AB  - Representative helicoidal conformations of polyglycine infinite chains have been
      investigated by using periodic boundary conditions, the B3LYP hybrid functional,
      and large basis sets, by means of the CRYSTAL code. The exploitation of the helix
      roto-translational symmetry permits to optimize at a relatively low cost the
      structure of systems whose unit cell contains more than 300 atoms, much larger
      than the one investigated till now. In the present calculations, the helix
      symmetry is exploited at three levels. First, for the automatic generation of the
      structure. Second, for the calculation of the one- and two-electron integrals
      that enter into the Fock matrix definition. Only the irreducible wedge of the
      Fock matrix is computed. Finally, for the diagonalization of the Fock matrix,
      where each irreducible representation is separately treated. The efficiency and
      accuracy of the computational scheme are documented, by considering cells
      containing up to 47 glycine residues. Results are compared with previous
      calculations and available experimental data. The role of hydrogen bonding in
      stabilizing polyglycine conformers is also addressed.

PMID- 20058228
TI  - Cognitive-nigrostriatal relationships in de novo, drug-naive Parkinson's disease
      patients: a [I-123]FP-CIT SPECT study.
AB  - To unveil cognitive-nigrostriatal correlations in Parkinson's disease (PD), 30 de
      novo, drug-naive PD patients and 15 patients with essential tremor (Controls,
      CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I
      123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of
      uptake at caudate and putamen level was conducted through the BasGan software,
      also allowing partial volume effect correction. Because of the multicollinearity
      among neuropsychological tests and among SPECT variables, factor analysis was
      applied to 16 neuropsychological scores; moreover, the four SPECT variables were
      merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS
      factors: a dys-executive (NPS-EX), a visuospatial (NPS-VS), a verbal memory (NPS
      VM), and a "mixed" (NPD-MIX) factor. In PD group, there were inverse correlations
      between UPDRS-III score and both NPS-VS (P < 0.01) and mSPECT (P < 0.05), and a
      direct correlation between mSPECT and NPS-EX (P < 0.05). Post hoc analysis showed
      a direct correlation between NPS-EX and caudate uptake in both hemispheres (P <
      0.05). Moreover, inverse correlations were found between UPDRS-III and,
      respectively, putamen uptake in the less affected hemisphere (P < 0.01), and
      putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no
      correlation was found between mSPECT and either NPS or GDS values. Nigro-caudate
      function affects executive capabilities in PD but not in CTR, which appears to be
      unrelated to the disease motor severity at its onset. Instead, PD motor severity
      is related to nigro-putaminal impairment and visuospatial dysfunction. The role
      of these data as predictive features of cognitive decline and eventually dementia
      remains to be established in longitudinal studies.

PMID- 20058229
TI  - Thermal dissociation of tripropylamine as the first step in the growth of carbon
      nanotubes inside AlPO4-5 channels.
AB  - Tripropylamine (TPA) is a template for the synthesis of porous AlPO(4)-5, whose
      calcination in the absence of air leads to the formation of 4 A single-walled
      carbon nanotubes. The thermal dissociation of TPA is the first step in this
      remarkable process. We examined the dissociation mechanisms of TPA by first
      principles calculations, under three types of conditions. In the gas phase, the
      unimolecular dissociation was a complex process initiated by the breaking of
      either the N-C(alpha) and the C(alpha)-C(beta) bonds. Within a confined space
      inside neutral zeolitic channels, the diffusion of H radicals enhanced a cycle of
      reactions to produce dipropylamine and monopropylamine, in agreement with
      experimental observations. In the presence of an acidic site, the dissociation of
      TPA was catalyzed to produce ammonia and propylene molecules, which were
      identified as the precursors for the eventual formation of carbon nanotubes.

PMID- 20058230
TI  - In situ hybridization of neuropeptide-encoding transcripts afp-1, afp-3, and afp
      4 in neurons of the nematode Ascaris suum.
AB  - The gene transcripts encoding both the AF8 and AF2 neuropeptides of the nematode
      Ascaris suum have been identified, cloned, and sequenced. The AF8 transcript (afp
      3) encodes five identical copies of AF8; each peptide-encoding region is flanked
      by the appropriate dibasic or monobasic cleavage processing sites. The AF2
      transcript (afp-4) encodes three identical copies of AF2 along with the
      appropriate cleavage sites. In contrast, the afp-1 transcript (Edison et al.
      [1997] Peptides 18:929-935) encodes six different AF peptides (AF3, 4, 10, 13,
      14, 20) which all share a -PGVLRFamide C-terminus but have different N-terminal
      sequences. By using in situ hybridization, gene transcript expression patterns of
      afp-1, afp-3, and afp-4 (As-flp-18, As-flp-6, and As-flp-14, respectively, in the
      naming convention proposed by Blaxter et al. [1997] Parasitol Today 13:416-417)
      were determined in the adult A. suum anterior nervous system. Each gene
      transcript can be localized to a different subset of neurons. These subsets of
      neurons are different from the subsets of Caenorhabditis elegans neurons that
      were shown to express identical or similar peptides by the use of promoter GFP
      constructs (Kim and Li [2004] J Comp Neurol 475:540-550).

PMID- 20058231
TI  - Mechanisms underlying catabolic and anabolic functions of parathyroid hormone on
      bone by combination of culture systems of mouse cells.
AB  - Since bone resorption and formation by continuous and intermittent parathyroid
      hormone (PTH) treatments involve various types of cells in bone, this study
      examined the underlying mechanism by combining culture systems using mouse
      primary calvarial osteoblasts and bone marrow cells. The PTH/PTHrP receptor
      (PTH1R) expression and the cAMP accumulation in response to PTH were increased in
      accordance with the differentiation of osteoblasts. Osteoclast formation was
      strongly induced by continuous PTH treatment in the monolayer co-culture of
      osteoblasts and bone marrow cells, which was associated with RANKL expression in
      differentiated osteoblasts. Bone formation determined by ALP activity and the
      type I collagen mRNA expression was stimulated by intermittent PTH treatment in
      the monolayer co-culture and in the bone marrow cell layer of the separated co
      culture in a double chamber dish, but not in the culture of bone marrow cells
      alone. The stimulation in the separated co-culture, accompanied by IGF-I
      production by osteoblasts, was abolished when bone marrow cells were derived from
      knockout mice of insulin-receptor substrate-1 (IRS-1-/-) or when osteoblasts were
      from PTH1R-/- mice. We conclude that differentiated osteoblasts are most likely
      the direct target of both continuous and intermittent PTH, while bone marrow
      cells are likely the effector cells. The osteoblasts stimulated by continuous PTH
      express RANKL which causes osteoclastogenesis from the precursors in bone marrow
      via cell-to-cell contact, leading to bone resorption; while the osteoblasts
      stimulated by intermittent PTH secrete IGF-I which activates IRS-1 in osteoblast
      precursors in bone marrow via a paracrine mechanism, leading to bone formation.

PMID- 20058232
TI  - The 19S proteasomal lid subunit POH1 enhances the transcriptional activation by
      Mitf in osteoclasts.
AB  - The microphthalmia-associated transcription factor (Mitf) regulates gene
      expression required for osteoclast differentiation. Genes regulated by Mitf have
      been previously identified. However, proteins that interact and regulate Mitf's
      activity in osteoclasts are not well known. Here, we report that POH1, a subunit
      of the 19S proteasome lid is a regulator of Mitf. We show that POH1 and Mitf
      interact in osteoclasts and that this interaction is dependent on RANKL
      signaling. Overexpression of POH1 increased Mitf's activation of 5XGal4-TK and
      Acp5 promoters. The amino terminus of POH1 mediates the binding to Mitf and is
      sufficient to increase Mitf's transcriptional activity. Finally, we show that
      mutations in the JAMM motif of POH1 reduced Mitf activation of promoters. In
      summary, our results identify a novel mechanism of Mitf regulation in osteoclasts
      by POH1.

PMID- 20058233
TI  - Nuclear inositide signaling in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are defined as clonal hematopoietic stem-cell
      disorders characterized by ineffective hematopoiesis in one or more of the
      lineages of the bone marrow. Although distinct morphologic subgroups exist, the
      natural history of MDS is progression to acute myeloid leukemia (AML). However,
      the molecular the mechanisms the underlying MDS evolution to AML are not
      completely understood. Inositides are key cellular second messengers with well
      established roles in signal transduction pathways, and nuclear metabolism
      elicited by phosphoinositide-specific phospholipase C (PI-PLC) beta1 and Akt
      plays an important role in the control of the balance between cell cycle
      progression and apoptosis in both normal and pathologic conditions. Recent
      findings evidenced the role played by nuclear lipid signaling pathways, which
      could become promising therapeutic targets in MDS. This review will provide a
      concise and updated revision of the state of art on this topic.

PMID- 20058234
TI  - Defining topological features of membrane proteins by nanoelectrospray ionisation
      mass spectrometry.
AB  - The D-galactose-H(+) symport protein, GalP, of Escherichia coli is the bacterial
      homologue of the human glucose transport protein, GLUT1. Here we demonstrate that
      mass spectrometry can be used to map modification by covalently bound reagents,
      and also to detect structural changes in the GalP protein that occur upon
      substrate binding. The small thiol-group-specific reagent N-ethylmaleimide (NEM)
      was used to modify the cysteine residues in GalP(His)(6) both alone and in the
      presence of D-glucose, a known substrate. Employing a mixture of proteolysis and
      thermal degradation methods, the three cysteine residues were found to undergo
      sequential reactions with NEM, with Cys374 being modified first, followed by
      Cys389 and finally Cys19, thus indicating their different accessibilities within
      the three-dimensional structure of the protein. Prior binding of the substrate D
      glucose to the protein protected Cys19 and Cys374 against NEM modification, but
      not Cys389. Cys374 had been expected to be shielded by D-glucose binding while
      Cys389 had been expected to be unaffected, consistent with their proposed
      respective locations in the vicinity of, and distant from, the sugar binding
      site. However, the inaccessibility of Cys19 was unexpected and suggests a
      structural change in the protein promoted by D-glucose binding which changes the
      proximity of Cys19 with respect to the D-glucose-binding site.

PMID- 20058235
TI  - Stable isotope analysis of dissolved organic carbon in soil solutions using a
      catalytic combustion total organic carbon analyzer-isotope ratio mass
      spectrometer with a cryofocusing interface.
AB  - Stable carbon isotopes are a powerful tool to assess the origin and dynamics of
      carbon in soils. However, direct analysis of the (13)C/(12)C ratio in the
      dissolved organic carbon (DOC) pool has proved to be difficult. Recently, several
      systems have been developed to measure isotope ratios in DOC by coupling a total
      organic carbon (TOC) analyzer with an isotope ratio mass spectrometer. However
      these systems were designed for the analysis of fresh and marine water and no
      results for soil solutions or (13)C-enriched samples have been reported. Because
      we mainly deal with soil solutions in which the difficult to oxidize humic and
      fulvic acids are the predominant carbon-containing components, we preferred to
      use thermal catalytic oxidation to convert DOC into CO(2). We therefore coupled a
      high-temperature combustion TOC analyzer with an isotope ratio mass spectrometer,
      by trapping and focusing the CO(2) cryogenically between the instruments. The
      analytical performance was tested by measuring solutions of compounds varying in
      the ease with which they can be oxidized. Samples with DOC concentrations between
      1 and 100 mg C/L could be analyzed with good precision (standard deviation (SD) <
      or = 0.6 per thousand), acceptable accuracy, good linearity (overall SD = 1 per
      thousand) and without significant memory effects. In a (13)C-tracer experiment,
      we observed that mixing plant residues with soil caused a release of plant
      derived DOC, which was degraded or sorbed during incubation. Based on these
      results, we are confident that this approach can become a relatively simple
      alternative method for the measurement of the (13)C/(12)C ratio of DOC in soil
      solutions.

PMID- 20058237
TI  - Prolonged treatment with bicalutamide induces androgen receptor overexpression
      and androgen hypersensitivity.
AB  - BACKGROUND: Various hormone refractory prostate cancer cell models have been
      established with androgen depletion and have helped to clarify the mechanism for
      the transition into androgen-depletion independent status. However, the mechanism
      of bicalutamide resistance remains unclear because few cell models have been
      generated. METHODS: We generated a bicalutamide-resistant subline, LNCaP-BC2,
      from LNCaP after prolonged treatment with bicalutamide. Androgen and/or
      bicalutamide responsiveness for proliferation and prostate-specific antigen (PSA)
      secretion were examined in vitro and in vivo. Testosterone and
      dihydrotestosterone (DHT) levels in xenografted tumors were analyzed by liquid
      chromatography-tandem mass spectrometry. Androgen receptor (AR) gene mutation and
      amplification and AR and pAR(210) expression were determined. RESULTS: LNCaP-BC2
      did not grow in an androgen-depleted medium and proliferation was stimulated in a
      tenfold lower concentration of androgen than that of LNCaP. LNCaP-BC2 grew in
      castrated male mice, and the DHT level in grafted LNCaP-BC2 tumors was 7.7-fold
      lower than in LNCaP tumors. Bicalutamide stimulated LNCaP-BC2 proliferation and
      PSA secretion in vitro and the antitumor activity of bicalutamide against LNCaP
      BC2 was weaker than that of LNCaP in vivo. Additional AR mutation and AR gene
      amplification were not detected in LNCaP-BC2, but AR and pAR(210) expression and
      PSA secretion in LNCaP-BC2 were higher than in LNCaP. CONCLUSIONS: Bicalutamide
      resistant LNCaP-BC2 exhibited AR overexpression and hypersensitivity to low
      levels of androgen. Our data suggests that AR overexpression is a significant
      mechanism of bicalutamide resistance similar to resistance from chronic androgen
      depletion. In addition, pAR(210) overexpression could be a potential mechanism
      for hypersensitivity to low androgen in LNCaP-BC2.

PMID- 20058236
TI  - Molecular characterization of the Ggamma-globin-Tag transgenic mouse model of
      hormone refractory prostate cancer: comparison to human prostate cancer.
AB  - BACKGROUND: Prostate cancer (PrCa) has a high incidence in Western countries and
      at present, there is no cure for hormone refractory prostate cancer. Transgenic
      mouse models have proven useful for understanding mechanisms of prostate
      carcinogenesis. The characterization of genetically modified mouse PrCa models
      using high-throughput genomic analyses provides important information to guide
      appropriate experiment applications for such model. METHODS: We have analyzed the
      transcriptome of the hormone refractory and highly metastatic Fetal Globin-SV40/T
      antigen (Ggamma-globin-Tag) transgenic mouse model for PrCa compared to normal
      mouse prostate tissue. Gene expression patterns found in Ggamma-globin-Tag mouse
      prostate tumors were compared with publicly available human localized and
      metastatic prostate tumors (GEO accession # GSE3325) through hierarchical cluster
      analysis, Pearson's rank correlation coefficient, and Self Organizing Feature
      Maps (SOM) analyses. RESULTS: Ggamma-globin-Tag tumors clustered closely with
      human metastatic tumors and gene expression patterns had a significant
      correlation (P < 0.01), unlike human localized primary tumors (P > 0.6).
      Bioinformatic analyses identified deregulated genetic pathways and networks in
      Ggamma-globin-Tag tumors, which displayed similarities to alterations in human
      PrCa. Changes in the expression of genes involved in DNA replication and repair
      (Rb1, p53, Myc, PCNA, DNMT3A) and growth factor signaling pathways (TGFbeta2,
      ERK1/2, NRas, and Notch1) are deregulated in the Ggamma-globin-Tag tumors,
      suggesting their key role in the oncogenic process. Identification of an
      enrichment of putative binding sites for transcription factors revealed eight
      transcription factors that may be important in Ggamma-globin-Tag carcinogenesis,
      including SP1, NF-Y, CREB, Elk1, and E2F. Novel genes related to microtubule
      regulation were also identified in Ggamma-globin-Tag tumors as potentially
      important candidate targets for PrCa. Overexpression of stathmin-1, whose
      expression was increased in human metastatic prostate tumors, was validated in
      Ggamma-globin-Tag tumors by immunohistochemistry. This protein belongs to the
      SV40/T-antigen cancer signature identified in previous studies in prostate,
      breast, and lung cancer mouse models. CONCLUSIONS: Our results show that the
      Ggamma-globin-Tag model for hormone refractory PrCa shares important features
      with aggressive, metastatic human PrCa. Given the role of stathmin-1 in the
      destabilization of microtubles and taxane resistance, the Ggamma-globin-Tag model
      and other SV40/T-antigen driven transgenic models may be useful for testing
      potential therapies directed at stathmin-1 in human prostate tumors.

PMID- 20058238
TI  - Prostate-specific antigen (PSA) is activated by KLK2 in prostate cancer ex vivo
      models and in prostate-targeted PSA/KLK2 double transgenic mice.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a serine protease secreted as a
      zymogen. Previously, cell-free biochemical studies have identified various
      kallikreins (KLK) as candidate activating proteases. In this study, KLK2-mediated
      activation of PSA in cell-based in vitro, xenograft, and transgenic models was
      evaluated. METHODS: Du145-derived PSA- or KLK2-expressing clones were coincubated
      in vitro and in vivo to evaluate KLK2-induced PSA activity. While mice possess
      orthologs of KLK4-15, they do not have functional orthologs of PSA or KLK2.
      Therefore, transgenic animals expressing PSA or both PSA and KLK2 were generated
      to assess orthotopic PSA activation. RESULTS: PSA is activated by KLK2 when the
      cells are physically in contact, and through co-conditioned media. In vivo, the
      free (inactive PSA) to total (active + inactive PSA) ratio in the blood is
      decreased when PSA and KLK2-expressing cells are co-inoculated subcutaneously,
      suggesting increased active PSA. Additionally, double-transgenic mice expressing
      both genes in the prostate produce more active PSA compared to single transgenic
      animals. A longitudinal evaluation over a 2-year period demonstrated no
      morphologic changes (i.e., no PIN or prostate cancer) due to PSA or PSA/KLK2
      double transgene expression relative to non-transgenic mice. CONCLUSIONS: These
      data demonstrate, with biologically relevant models, that KLK2 is the protease
      responsible for activating PSA. While PSA is involved in the processing and
      release of a number of important growth factors, our results suggest that active
      PSA is not sufficient to induce the development of prostate cancer or prostate
      cancer precursors in aging PSA transgenic mice.

PMID- 20058239
TI  - The role of PI 3-kinase p110beta in AKT signally, cell survival, and
      proliferation in human prostate cancer cells.
AB  - BACKGROUND: Class IA PI 3-kinases produce phosphatidylinositol (3,4,5)
      trisphosphate (PIP3). PIP3 is bound by AKT which facilities its activation by
      PDK1. Activated AKT promotes cell survival and stimulates cell proliferation.
      Class IA PI 3-kinases are heterodimers consisting of a regulatory subunit p85 and
      a catalytic subunit p110. The p110alpha isoform has been shown to be mutated in a
      number of tumor types. A number of recent studies suggest that the p110beta
      isoform may be functionally relevant in prostate cancer. In this study we extend
      this work to include the examination of the expression and functional properties
      of p110alpha and p110beta in three different prostate cancer cell lines, DU145,
      LNCaP, PC3, as well as the non-tumorigenic but immortalized RWPE1 prostate
      epithelial cell line. METHODS: Western blot analysis was used to measure protein
      expression and quantitative real-time PCR was used to measure mRNA levels. After
      targeted knockdown using isoform-specific siRNAs to reduce PI 3-kinase p110alpha
      or p110beta isoform expression, we measured downstream signally events such as
      phosphorylation of AKT, ERK 1/2, PDK, and FOXO, as well as biological
      consequences such as changes in apoptosis, and alterations in cell cycle
      progression. RESULTS: In all three prostate cancer cell lines examined, targeted
      knockdown of p110beta, and not p110alpha, resulted in significantly reduced AKT,
      PDK, and FOXO phosphorylation. While knockdown of either p110 isoform resulted in
      an increase in apoptosis and a cell cycle arrest in G1 in the remaining non
      apoptotic cells, these effects were much more pronounced with knockdown of
      p110beta. CONCLUSIONS: Our results support the concept that p110beta appears to
      be the predominant functional class I PI 3-kinase isoform in prostate cancer
      cells.

PMID- 20058241
TI  - Generalized worry disorder: a review of DSM-IV generalized anxiety disorder and
      options for DSM-V.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) has undergone a series of
      substantial classificatory changes since its first inclusion in DSM-III. The
      majority of these revisions have been in response to its poor inter-rater
      reliability and concerns that it may lack diagnostic validity. This article
      provides options for the revision of the DSM-IV GAD criteria for DSM-V. METHOD:
      First, searches were conducted to identify the evidence that previous DSM Work
      Groups relied upon when revising the DSM-III-R GAD and the overanxious disorder
      classifications. Second, the literature pertaining to the DSM-IV criteria for GAD
      was examined. CONCLUSIONS: The review presents a number of options to be
      considered for DSM-V. One option is for GAD to be re-labeled in DSM-V as
      generalized worry disorder. This would reflect its hallmark feature. Proposed
      revisions would result in a disorder that is characterized by excessive anxiety
      and worry generalized to a number of events or activities for 3 months or more.
      Worry acts as a cognitive coping strategy that manifests in avoidant behaviors.
      The reliability and validity of the proposed changes could be investigated in DSM
      V validity tests and field trials.

PMID- 20058240
TI  - New potential anti-cancer agents synergize with bortezomib and ABT-737 against
      prostate cancer.
AB  - BACKGROUND: We previously described the identification of a transcriptional
      inhibitor ARC and FoxM1 inhibitors, thiazole antibiotics, Siomycin A and
      thiostrepton that were able to induce potent p53-independent apoptosis in cancer
      cell lines of different origin. Here, we report the characterization of these
      drugs individually or in combination with ABT-737 and bortezomib on a panel of
      prostate cancer cell lines. METHODS: DU 145, LNCaP and PC-3 prostate cancer cells
      were treated with ARC, Siomycin A and thiostrepton to evaluate their activity as
      single agents or in combination with ABT-737 and bortezomib to measure their
      synergistic potential in anti-proliferative and cell cycle assays. Chou-Talalay
      method was used to quantitate the synergistic interaction. Western blot method
      was used to determine Mcl-1 and FoxM1 expression and caspase-3 cleavage. RESULTS:
      We show that ARC inhibited the viability of prostate cancer cells and induced
      apoptosis in low nanomolar concentration. It potently downregulated the
      expression of Mcl-1 and showed synergistic combination effect with Bcl-2
      inhibitor ABT-737. Thiazole antibiotics, Siomycin A and thiostrepton inhibited
      growth, FoxM1 expression and induced cell death in prostate cancer cells in low
      micromolar concentrations. In addition, thiostrepton and ARC synergistically
      induced apoptosis in prostate cancer cells following combination treatment with
      proteasome inhibitor bortezomib. Furthermore, we found that all tested drug
      combinations were able to induce apoptosis selectively in transformed, but not
      normal cells of the same origin. CONCLUSIONS: Based on their in vitro activity as
      single or combination agents, ARC, Siomycin A and thiostrepton represent
      potential candidates for drug development against prostate cancer.

PMID- 20058242
TI  - Social anxiety disorder in adults who stutter.
AB  - BACKGROUND: The nature and prevalence of social anxiety disorder (social phobia
      (SP)) in people who stutter is uncertain, and DSM-IV differential diagnosis
      guidelines make it difficult to classify an adult who stutters (AWS) with SP as
      it is assumed any social anxiety symptoms will be a consequence of their
      stuttering. The aim of this study was to determine the spot prevalence of SP in
      AWS and to investigate differences in social anxiety between AWS and controls who
      do not stutter. METHODS: The study involved a comprehensive assessment of 200 AWS
      and 200 adults who do not stutter similar in age and sex ratio. Measures included
      stuttering severity, health status, self-report measures of social anxiety as
      well as a structured diagnostic interview for SP for randomly selected sub-group
      of 50 from each group. RESULTS: The AWS were found to have significantly raised
      trait and social anxiety, as well as significantly increased risk of SP in
      comparison to the controls. Findings indicated a SP spot prevalence of at least
      40% in AWS, and for them to be at high risk of having Generalized SP.
      CONCLUSIONS: It is concluded that the DSM-IV diagnostic guidelines for diagnosing
      SP in AWS could result in professional confusion and have possible negative
      mental health ramifications. Implications for the psychological and medical
      treatment of AWS are discussed.

PMID- 20058243
TI  - Silk fibroin microparticles as carriers for delivery of human recombinant BMPs.
      Physical characterization and drug release.
AB  - Bone morphogenetic proteins (BMPs) are cytokines with strong ability to promote
      new bone formation. Herein, we report the use of silk fibroin microparticles as
      carriers for the delivery of BMP-2, BMP-9 or BMP-14. BMP-containing fibroin
      microparticles were prepared by a mild methodology using dropwise addition of
      ethanol, exhibiting mean diameters of 2.7 +/- 0.3 microm. Encapsulation
      efficiencies varied between 67.9 +/- 6.1 % and 97.7 +/- 2.0 % depending on the
      type and the amount of BMP loaded. Release kinetics showed that BMP-2, BMP-9 and
      BMP-14 were released in two phases profile, with a burst release in the first two
      days followed by a slower release, for a period of 14 days. The release data were
      best explained by Korsmeyer's model and the Fickian model of drug diffusion. Silk
      fibroin microparticles can offer a promising approach for the sustained delivery
      of different BMPs in tissue engineering applications.

PMID- 20058244
TI  - Dexamethasone treatment during the expansion phase maintains stemness of bone
      marrow mesenchymal stem cells.
AB  - Human mesenchymal stem cells (hMSCs) can form various mesodermal tissues when
      grown under appropriate conditions. Dexamethasone (Dex) is regularly used to
      stimulate the osteogenic potential of hMSCs and it has recently been reported to
      increase the cell expansion rate. In this study we have investigated the effect
      of low-dose Dex treatment (10(-8) M) on the multipotency of expanded hMSCs, using
      histological, biochemical and molecular biological techniques. Early passage (P2
      3) and late passage (P6) cells were positive (>90%) for mesenchymal adhesion cell
      markers (CD105/CD29/CD44/CD166/CD90) and negative (<10%) for haematopoietic
      markers (CD34/CD45/CD14). Dex did not change the overall expression pattern of
      these cell surface markers. Expanded hMSCs gave rise to specialized cell lineages
      when grown in differentiation-promoting medium. Depending on the donor, Dex
      treatment improved the potency for osteogenic, adipogenic and chondrogenic
      differentiation of expanded hMSCs. Dex also prevented the loss of proliferative
      potential of hMSCs upon sequential passaging and the loss of the typical hMSCs
      surface phenotype. hMSCs gene expression analysis showed that low-dose Dex
      negatively regulated transcription of genes correlated with apoptosis and
      differentiation, and positively regulated genes associated with cell
      proliferation. In conclusion, the collective data argue that low-dose Dex
      preserves the stemness of hMSCs during repeated passaging, as indicated by the
      maintenance of the stem cell phenotype, proliferative capacity and multi-lineage
      differentiation potential.

PMID- 20058245
TI  - Laryngotracheal reconstruction with porous titanium in rabbits: are vascular
      carriers and mucosal grafts really necessary?
AB  - Laryngotracheal reconstruction requires a supportive structure with a mucosal
      lining, which needs a vascular supply in order to regenerate properly. We
      investigated the necessity of a vascular carrier and mucosal graft when using
      porous titanium for laryngotracheal reconstruction. Surgical defects of the
      laryngotracheal complex in 22 rabbits were reconstructed with: (a) porous
      titanium implanted on a vascularized fascia combined with a buccal mucosal graft
      (first stage) before transposing to the neck area (second stage); (b) porous
      titanium implanted on a vascularized fascia (first stage) combined with a mucosal
      graft (second stage); (c) porous titanium on a pedicled fascia flap; and (d)
      porous titanium alone. The grafts were tolerated well. Re-epithelialization
      occurred in all groups. Normal mucosa with a submucosal layer containing vital
      cells was noted using the titanium implants. Blood vessels were grown in the
      pores of the titanium scaffold to supply the overlying mucosa. The scaffold was
      well integrated in the adjacent tracheal cartilage and surrounding tissues,
      except in the two cases that showed titanium displacement. Inflammation and
      granulation formation were seen in most rabbits in groups III and IV, initiated
      probably by the use of buccal mucosal grafts. Reconstruction of a rabbit's
      trachea using composites of porous titanium, mucosal grafts and a fascia flap is
      feasible. Titanium seems to meet the requirements needed for closing a small
      defect of the tracheal wall and allows for re-epithelialization. For larger
      defects, a vascular carrier with a mucosal graft is probably indispensable to
      ensure the process of re-epithelialization.

PMID- 20058246
TI  - ReSASC: a resampling-based algorithm to determine differential protein expression
      from spectral count data.
AB  - Label-free methods for MS/MS quantification of protein expression are becoming
      more prevalent as instrument sensitivity increases. Spectral counts (SCs) are
      commonly used, readily obtained, and increase linearly with protein abundance;
      however, a statistical framework has been lacking. To accommodate the highly non
      normal distribution of SCs, we developed ReSASC (resampling-based significance
      analysis for spectral counts), which evaluates differential expression between
      two conditions by pooling similarly expressed proteins and sampling from this
      pool to create permutation-based synthetic sets of SCs for each protein. At a set
      confidence level and corresponding p-value cutoff, ReSASC defines a new p-value,
      p', as the number of synthetic SC sets with p>p(cutoff) divided by the total
      number of sets. We have applied ReSASC to two published SC data sets and found
      that ReSASC compares favorably with existing methods while being easy to operate
      and requiring only standard computing resources.

PMID- 20058247
TI  - Rover: a tool to visualize and validate quantitative proteomics data from
      different sources.
AB  - Manual validation of regulated proteins found in MS-driven quantitative proteome
      studies is tedious. Here we present Rover (http://genesis.ugent.be/rover), a tool
      that facilitates this process. Rover accepts quantitative data from different
      sources such as MASCOT Distiller and MaxQuant and, in an intuitive environment,
      Rover visualizes these data such that the user can select and validate algorithm
      suggested regulated proteins in the frame of the whole experiment and in the
      context of the protein inference problem.

PMID- 20058248
TI  - ms_lims, a simple yet powerful open source laboratory information management
      system for MS-driven proteomics.
AB  - MS-based proteomics produces large amounts of mass spectra that require
      processing, identification and possibly quantification before interpretation can
      be undertaken. High-throughput studies require automation of these various steps,
      and management of the data in association with the results obtained. We here
      present ms_lims (http://genesis.UGent.be/ms_lims), a freely available, open
      source system based on a central database to automate data management and
      processing in MS-driven proteomics analyses.

PMID- 20058249
TI  - MS-driven protease substrate degradomics.
AB  - Proteolytic processing has recently received increased attention in the field of
      signal propagation and cellular differentiation. Because of its irreversible
      nature, protein cleavage has been associated with committed steps in cell
      function. One aspect of protease biology that boomed the past few years is the
      detailed characterization of protease substrates by both shotgun as well as
      targeted MS-driven proteomics techniques. The most promising techniques are
      discussed in this review and we further elaborate on the bioinformatics
      challenges that accompany mainly qualitative, MS-driven protease substrate
      degradome studies.

PMID- 20058250
TI  - jTraqX: a free, platform independent tool for isobaric tag quantitation at the
      protein level.
AB  - Many proteomic studies focus on quantitative aspects, using different stable
      isotope labeling techniques that require specialized software to analyze the
      generated data. Here we present jTraqX, an easy-to-use tool for processing and
      visualizing protein quantification data. jTraqX is platform independent and is
      compatible with all available 4-plex isobaric tags. jTraqX can be freely
      downloaded at http://sourceforge.net/projects/protms.

PMID- 20058251
TI  - Real-time monitoring of RNA synthesis in a phospholipid-coated microdroplet as a
      live-cell model.
AB  - We constructed a phospholipid-coated water-in-oil microdroplet (20-60 microm in
      diameter) that encapsulated plasmid DNA containing a human beta-actin cDNA
      sequence, fluorescent oligonucleotide probes, and other components of the
      transcription reaction. Transcription inside individual microdroplets was
      investigated in real time by using fluorescence microscopy. The progress of the
      transcription reaction was successively monitored by fluorescence resonance
      energy transfer (FRET), which was derived from the specific hybridization of
      fluorescent oligonucleotide probes to the beta-actin mRNAs synthesized. In
      microdroplets composed of phosphatidylethanolamine, DNAs were located in the
      aqueous phase or on the membrane surface depending on the Mg(II) concentration.
      FRET images showed that transcription occurred on DNA in both states. Moreover,
      individual DNA molecules undergoing transcription were visualized as discrete
      FRET signals in cases in which small numbers of DNAs were present in the
      microdroplet.

PMID- 20058252
TI  - Blue fluorescent amino acids as in vivo building blocks for proteins.
AB  - In vivo expression of colored proteins without post-translational modification or
      chemical functionalization is highly desired for protein studies and cell
      biology. Cell-permeable tryptophan analogues, such as azatryptophans, have proved
      to be almost ideal isosteric substitutes for natural tryptophan in cellular
      proteins. Their unique spectral features, such as markedly red-shifted
      fluorescence, are transmitted into protein structures upon incorporation. Among
      the azaindoles under study (2-, 4-, 5-, 6-, and 7-azaindole) 4-azaindole has
      exhibited the largest Stokes shift (approximately 130 nm) in steady-state
      fluorescence measurements. It is also highly biocompatible and as 4-azatryptophan
      it can be translated into target protein sequences. However, its quantum yield
      and fluorescence intensity are still significantly lower when compared with
      natural indole/tryptophan. Since azatryptophans are hydrophilic, their presence
      in the hydrophobic core of proteins could be harmful. In order to overcome these
      limitations we have performed nitrogen methylation of azaindoles and generated
      mono- and dimethylated azaindoles. Some of these methyl derivatives retain the
      pronounced red shift present in the parent 4-azaindole, but with much higher
      fluorescence intensity (reaching the level of indole/tryptophan). Therefore, the
      blue fluorescence of azaindole-containing proteins could be further enhanced by
      the use of methylated analogues. Further substitution of any azaindole ring with
      either endo- or exocyclic nitrogen will not yield a spectral fluorescence maximum
      shift beyond 450 nm under steady-state conditions in the physiological milieu.
      However, green fluorescence is a special feature of tautomeric species of
      azaindoles in various nonaqueous solvents. Thus, the design or evolution of the
      protein interior combined with the incorporation of these azaindoles might lead
      to the generation of specific chromophore microenvironments that facilitate
      tautomeric or protonated/deprotoned states associated with green fluorescence.

PMID- 20058254
TI  - Lower homologues of okoumal and disila-okoumal: synthesis and olfactory
      characterization of novel ambergris odorants.

PMID- 20058253
TI  - Unnatural polyketide analogues selectively target the HER signaling pathway in
      human breast cancer cells.
AB  - Receptor tyrosine kinases are critical targets for the regulation of cell
      survival. Cancer patients with abnormal receptor tyrosine kinases (RTK) tend to
      have more aggressive disease with poor clinical outcomes. As a result, human
      epidermal growth factor receptor kinases, such as EGFR (HER1), HER2, and HER3,
      represent important therapeutic targets. Several plant polyphenols including the
      type III polyketide synthase products (genistein, curcumin, resveratrol, and
      epigallocatechin-3-galate) possess chemopreventive activity, primarily as a
      result of RTK inhibition. However, only a small fraction of the polyphenolic
      structural universe has been evaluated. Along these lines, we have developed an
      in vitro route to the synthesis and subsequent screening of unnatural polyketide
      analogues with N-acetylcysteamine (SNAc) starter substrates and malonyl-coenzyme
      A (CoA) and methylmalonyl-CoA as extender substrates. The resulting polyketide
      analogues possessed a similar structural polyketide backbone (aromatic-2-pyrone)
      with variable side chains. Screening chalcone synthase (CHS) reaction products
      against BT-474 cells resulted in identification of several
      trifluoromethylcinnamoyl-based polyketides that showed strong suppression of the
      HER2-associated PI3K/AKT signaling pathway, yet did not inhibit the growth of
      nontransformed MCF-10A breast cells (IC(50)>100 microM). Specifically, 4
      trifluoromethylcinnamoyl pyrone (compound 2 e) was highly potent (IC(50)<200 nM)
      among the test compounds toward proliferation of several breast cancer cell
      lines. This breadth of activity likely stems from the ability of compound 2 e to
      inhibit the phosphorylation of HER1, HER2, and HER3. Therefore, these polyketide
      analogues might prove to be useful drug candidates for potential breast cancer
      therapy.

PMID- 20058255
TI  - The role of flexibility in the rational design of modularly assembled ligands
      targeting the RNAs that cause the myotonic dystrophies.
AB  - Modularly assembled ligands were designed to target the RNAs that cause two
      currently untreatable neuromuscular disorders, myotonic dystrophy types 1 (DM1)
      and 2 (DM2). DM1 is caused by an expanded repeating sequence of CUG, and DM2 is
      caused by expanded CCUG repeats. Both are present in noncoding regions and fold
      into hairpins with either repeating 1x1 nucleotide UU (DM1) or 2x2 nucleotide 5'
      CU/3'-UC (DM2) internal loops separated by two GC pairs. The repeats are toxic
      because they sequester the RNA splicing regulator muscleblind-like 1 protein
      (MBNL1). Rational design of ligands targeting these RNAs was enabled by a
      database of RNA motif-ligand partners compiled by using two-dimensional
      combinatorial screening (2DCS). One 2DCS study found that the 6''-azido-kanamycin
      A module binds internal loops similar to those found in DM1 and DM2. In order to
      further enhance affinity and specificity, the ligand was assembled on a peptoid
      backbone to precisely control valency and the distance between ligand modules.
      Designed compounds are more potent and specific binders to the toxic RNAs than
      MBNL1 and inhibit the formation of the RNA-protein complexes with nanomolar
      IC(50) values. This study shows that three important factors govern potent
      inhibition: 1) the surface area sequestered by the assembled ligands; 2) the
      spacing between ligand modules since a longer distance is required to target DM2
      RNAs than DM1 RNAs; and 3) flexibility in the modular assembly scaffold used to
      display the RNA-binding module. These results have impacts on the general design
      of assembled ligands targeting RNAs present in genomic sequence.

PMID- 20058256
TI  - Impact of dietary polyphenols on human platelet function--a critical review of
      controlled dietary intervention studies.
AB  - Cardiovascular disease is a chronic disease influenced by many factors, with
      activated blood platelets being one of them. Platelets play a central role in the
      formation of plaques within blood vessels, contributing to early inflammatory
      events. Consumption of diets rich in plant-based products protects against the
      development of cardiovascular disease. Polyphenols, which are secondary plant
      metabolites found in a wide range of foodstuffs and beverages, may be partially
      responsible for these effects. Their protective properties include inhibitory
      effects on platelet function in vitro and in vivo. However, the bioavailability
      of many polyphenols is poor and it is unclear whether sufficient quantities can
      be obtained by dietary means to exert protective effects. Consequently, this
      review summarizes 25 well-controlled human intervention studies examining the
      effect of polyphenol-rich diets on platelet function. These studies report a huge
      variety of research methods, study designs, and study subjects, resulting in
      controversial assertions. One consistent finding is that cocoa-related products,
      however, have platelet-inhibiting effects when consumed in moderate amounts. To
      assess whether other classes of dietary polyphenols, or their metabolites, also
      beneficially affect platelet function requires more well-controlled intervention
      studies as well as the adoption of more uniform methods to assess platelet
      aggregation and activation.

PMID- 20058257
TI  - Are the associations of plasma leptin and adiponectin with type 2 diabetes
      independent of obesity in older Chinese adults?
AB  - BACKGROUND: China has experienced a rapid increase in diabetes. In this study, we
      assessed whether the associations of two adipocyte-derived hormones, leptin and
      adiponectin, with type 2 diabetes are independent of obesity in older Chinese
      adults. METHODS: In this matched case-control study, each of the 619 diabetes and
      impaired fasting glucose (IFG) cases aged 60-96 years was matched to a control by
      age, sex, waist circumference and body mass index (BMI). RESULTS: Before
      matching, IFG and diabetes cases had significantly lower adiponectin and higher
      leptin concentrations than the participants with normal glucose. After matching
      for age, sex, waist circumference and BMI, the differences between cases and
      controls remained significant (p < 0.001) in adiponectin but not in leptin (p =
      0.77). Adjusted odds ratios for the combined outcome of diabetes and IFG were
      1.03 (95% confidence interval: 0.88, 1.21; p = 0.71) for one standard deviation
      increase in plasma leptin and 0.79 (95% confidence interval: 0.69, 0.91; p <
      0.001) for one standard deviation increase in plasma adiponectin. CONCLUSION:
      Without adjustment for obesity related body size measurements of waist
      circumference and BMI, both adiponectin and leptin are associated with diabetes
      and IFG. After adjustment, adiponectin is independently associated with diabetes
      and IFG, but there is no independent association between leptin and either
      diabetes or IFG. Our findings suggest that adiponectin provides extra-predictive
      power beyond obesity while leptin does not independently predict the risk of
      diabetes and IFG in older Chinese adults.

PMID- 20058258
TI  - EPR/spin-trapping study of free radical intermediates in the photolysis of
      trifluoromethyl ketones with initiators.
AB  - Photolysis of trifluoromethyl ketones (TFMKs) 1a-1e versus the non-fluorinated
      ketones 2a-2b in the presence of radical initiators by electron paramagnetic
      resonance spectroscopy has been studied for the first time. The transient
      radicals generated after irradiation of the ketones were identified by trapping
      with 2-methyl-2-nitrosopropane (MNP) and 2,4,6-tri-tert-butylnitrosobenzene
      (TTBNB) as spin traps. TTBNB is a powerful, particularly useful spin trap in
      these kinds of processes producing anilino and nitroxyl spin adducts due to the
      ambivalent reactivity on the N and O atoms. In the presence of t-butylperoxide,
      short-chain TFMKs, such as 1,1,1-trifluoroacetone (1d) and hexafluoroacetone
      (1e), give rise to detection of the elusive trifluoromethyl radical. In contrast,
      long-chain TFMKs did not provide clues to prove formation of the trifluoromethyl
      radical but instead to radicals derived by abstraction of one alpha-methylene
      proton to the carbonyl. Although TFMKs are quite stable to photodegradation in
      the absence of initiator, methyl ketone 2b and phenyl ketone 3 produce radicals
      resulting from abstraction of a gamma-hydrogen to the carbonyl group.

PMID- 20058259
TI  - A cellular level approach to predicting resting energy expenditure: Evaluation of
      applicability in adolescents.
AB  - We previously derived a cellular level approach for a whole-body resting energy
      expenditure (REE) prediction model by using organ and tissue mass measured by
      magnetic resonance imaging (MRI) combined with their individual cellularity and
      assumed stable-specific resting metabolic rates. Although this approach predicts
      REE well in both young and elderly adults, there were no studies in adolescents
      that specifically evaluated REE in relation to organ-tissue mass. It is unclear
      whether the approach can be applied to rapidly growing adolescents. The aim of
      the present study was to evaluate the applicability of the previous developed REE
      prediction model in adolescents, and to compare its applicability in young and
      elderly adults. Specifically, we tested the hypothesis that measured REE can be
      predicted from a combination of individual organ and tissue mass and their
      related cellularity. This was a 2-year longitudinal investigation. Twenty healthy
      male subjects with a mean age of 14.7 years had REE, organ and tissue mass, body
      cell mass, and fat-free mass (FFM) measured by indirect calorimetry, whole-body
      MRI, whole-body (40)K counting and dual-energy X-ray absorptiometry,
      respectively. The predicted REE (REEp; mean +/- SD, 1,487 +/- 238 kcal/day) was
      correlated with the measured REE (REEm, 1,606 +/- 237 kcal/day, r = 0.76, P <
      0.001). The mean difference (118 +/- 165 kcal/day) between REEm and REEp was
      significant (P = 0.0047), accounting for 7.3% of REEm for the entire group. The
      present study, the first of its type in adolescents, does not support the
      applicability of the organ-tissue-based REE prediction model during rapid
      adolescent growth. A modified general REE prediction model is thus suggested
      which may account for the higher REE/FFM ratio observed in adolescents.

PMID- 20058260
TI  - Penetration depth method--novel real-time strategy for evaluating
      femoroacetabular impingement.
AB  - We introduce a new method for computerized real-time evaluation of
      femoroacetabular impingement (FAI). In contrast to previously presented stress
      analyses, this method is based on two types of predictions of penetration depths
      for two rotating bodies: curvilinear and radial penetration depth. This intuitive
      method allows the analysis of both bony and soft tissue structures (such as
      cartilage and acetabular labrum) in real time. Characteristic penetration depth
      patterns were found for different subtypes of FAI, such as cam and pincer
      pathologies. In addition, correlation between the penetration depths (estimated
      by applying this method) and the existing contact stresses (estimated by applying
      the finite element method) of various hip morphologies were found. A strong
      correlation with predicted stress values existed, with a mean correlation
      coefficient of 0.91 for the curvilinear and 0.80 for the radial penetration
      method. The results show that the penetration depth method is a promising, fast,
      and accurate method for quantification and diagnosis of FAI.

PMID- 20058261
TI  - Changes in knee adduction moment, pain, and functionality with a variable
      stiffness walking shoe after 6 months.
AB  - This study tested the effects of variable-stiffness shoes on knee adduction
      moment, pain, and function in subjects with symptoms of medial compartment knee
      osteoarthritis over 6 months. Patients were randomly and blindly assigned to a
      variable-stiffness intervention or constant-stiffness control shoe. The Western
      Ontario and McMaster Universities (WOMAC) score served as the primary outcome
      measure. Joint loading, the secondary outcome measure, was assessed using the
      external knee adduction moment. Peak external knee adduction moment, total WOMAC,
      and WOMAC pain scores were assessed at baseline and after 6 months. The total
      WOMAC and WOMAC pain scores for the intervention group were reduced from baseline
      to 6 months (p = 0.017 and p = 0.002, respectively), with no significant
      reductions for the control group. There was no difference between groups in
      magnitude of the reduction in total WOMAC (p = 0.50) or WOMAC pain scores (p =
      0.31). The proportion of patients achieving a clinically important improvement in
      pain was greater in the intervention group than in the control group (p = 0.012).
      The variable-stiffness shoes reduced the peak knee adduction moment (-6.6% vs.
      control, p < 0.001) in the 34 intervention subjects at 6 months. The adduction
      moment reduction significantly improved (p = 0.03) from the baseline reduction.
      The constant-stiffness control shoe increased the peak knee adduction moment
      (+6.3% vs. personal, p = 0.004) in the 26 control subjects at 6 months. The
      results of this study showed that wearing the variable-stiffness shoe lowered the
      adduction moment, reduced pain, and improved functionality after 6 months of
      wear. The lower adduction moment associated with wearing this shoe may slow the
      rate of progression of osteoarthritis after long-term use.

PMID- 20058263
TI  - Compression therapy promotes proliferative repair during rat Achilles tendon
      immobilization.
AB  - Achilles tendon ruptures are treated with an initial period of immobilization,
      which obstructs the healing process partly by a reduction of blood circulation.
      Intermittent pneumatic compression (IPC) has been proposed to enhance tendon
      repair by stimulation of blood flow. We hypothesized that daily IPC treatment can
      counteract the deficits caused by 2 weeks of immobilization post tendon rupture.
      Forty-eight Sprague-Dawley SD) rats, all subjected to blunt Achilles tendon
      transection, were divided in three equal groups. Group A was allowed free cage
      activity, whereas groups B-C were immobilized at the operated hindleg. Group C
      received daily IPC treatment. Two weeks postrupture the rats were euthanatized
      and the tendons analyzed with tensile testing and histological assessments of
      collagen organization and collagen III-LI occurrence. Immobilization
      significantly reduced maximum force, energy uptake, stiffness, tendon length,
      transverse area, stress, organized collagen diameter and collagen III-LI
      occurrence by respectively 80, 75, 77, 22, 47, 65, 49, and 83% compared to free
      mobilization. IPC treatment improved maximum force 65%, energy 168%, organized
      collagen diameter 50%, tendon length 25%, and collagen III-LI occurrence 150%
      compared to immobilization only. The results confirm that immobilization impairs
      healing after tendon rupture and furthermore demonstrate that IPC-treatment can
      enhance proliferative tendon repair by counteracting biomechanical and
      morphological deficits caused by immobilization.

PMID- 20058262
TI  - Oxidant conditioning protects cartilage from mechanically induced damage.
AB  - Articular cartilage degeneration in osteoarthritis has been linked to abnormal
      mechanical stresses that are known to cause chondrocyte apoptosis and metabolic
      derangement in in vitro models. Evidence implicating oxidative damage as the
      immediate cause of these harmful effects suggests that the antioxidant defenses
      of chondrocytes might influence their tolerance for mechanical injury. Based on
      evidence that antioxidant defenses in many cell types are stimulated by moderate
      oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute
      chondrocyte death and proteoglycan depletion in cartilage explants after exposure
      to abnormal mechanical stresses. Porcine cartilage explants were treated every 48
      h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100,
      250, and 500 microM) for a varying number of times (one, two, or four) prior to a
      bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared
      with untreated controls, tBHP had significant positive effects on post
      compression viability, lactate production, and proteoglycan losses. Overall, the
      most effective regime was 100 microM tBHP applied four times. RNA analysis
      revealed significant effects of 100 microM tBHP on gene expression. Catalase,
      hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate
      dehydrogenase (GAPDH) were significantly increased relative to untreated controls
      in explants treated four times with 100 microM tBHP, a regime that also resulted
      in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These
      findings demonstrate that repeated exposure of cartilage to sublethal
      concentrations of peroxide can moderate the acute effects of mechanical stress, a
      conclusion supported by evidence of peroxide-induced changes in gene expression
      that could render chondrocytes more resistant to oxidative damage.

PMID- 20058264
TI  - Effect of glenohumeral abduction angle on the mechanical interaction between the
      supraspinatus and infraspinatus tendons for the intact, partial-thickness torn,
      and repaired supraspinatus tendon conditions.
AB  - Rotator cuff tears are difficult to manage because of the structural and
      mechanical inhomogeneity of the supraspinatus tendon. Previously, we showed that
      with the arm at the side, the supraspinatus and infraspinatus tendons
      mechanically interact such that conditions that increase supraspinatus tendon
      strain, such as load or full-thickness tears, also increase infraspinatus tendon
      strain. This suggests that the infraspinatus tendon may shield the supraspinatus
      tendon from further injury while becoming at increased risk of injury itself. In
      this study, the effect of glenohumeral abduction angle on the interaction between
      the two tendons was evaluated for supraspinatus tendon partial-thickness tears
      and two repair techniques. Principal strains were quantified in both tendons for
      0 degrees , 30 degrees , and 60 degrees of glenohumeral abduction. Results showed
      that interaction between the two tendons is interrupted by an increase in
      abduction angle for all supraspinatus tendon conditions evaluated. Infraspinatus
      tendon strain was lower at 30 degrees and 60 degrees than at 0 degrees abduction
      angle. In conclusion, interaction between the supraspinatus and infraspinatus
      tendons is interrupted with increase in abduction angle. Additionally, 30 degrees
      abduction should be further evaluated for management of rotator cuff tears and
      repairs as it is the angle at which both supraspinatus and infraspinatus tendon
      strain is decreased.

PMID- 20058266
TI  - Mesenchymal stem cells accelerate bone allograft incorporation in the presence of
      diabetes mellitus.
AB  - Allograft (Allo) incorporation in the presence of a systemic disease like
      diabetes mellitus (DM) is becoming a major issue in the orthopedic community.
      Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from
      adult, whole bone marrow and have been shown to induce bone formation in
      segmental defects when combined with the appropriate carrier/scaffold. The
      objectives of this study were to analyze the effect of DM upon Allo incorporation
      in a segmental rat femoral defect and to also investigate MSC augmentation of
      Allo incorporation. Segmental (5 mm) femoral defects were created in non-DM and
      DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM
      with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature
      bone in the DM/DBM group compared to its non-DM counterpart (p < 0.001). However,
      there was significantly more mature bone in the DM/MSC group when compared to the
      DM/DBM group at both 4 and 8 weeks (p < 0.001 and p = 0.004). Furthermore,
      significantly more bone formation was observed in the DM/MSC group compared to
      the DM/DBM group at the 4-week time point (p < 0.001). The results of this study
      suggest that MSC are a potential adjunct for bone regeneration when implanted in
      an orthotopic site in the presence of DM.

PMID- 20058265
TI  - Agonist-selective signaling of G protein-coupled receptor: mechanisms and
      implications.
AB  - Agonist-selective signaling or ligand-biased signaling of G protein-coupled
      receptor (GPCR) has become the focus of an increasing number of laboratories. The
      principle of this concept is that agonist possesses different abilities to
      activate different signaling pathways. Current review summarizes the observations
      of agonist-selective signaling of various GPCRs, indicating the significance of
      agonist-selective signaling in biological processes. In addition, current review
      also provides an overview on how agonist-selective signaling is initiated.
      Especially, the relationship between GPCR-G protein interaction and GPCR-beta
      arrestin interaction is discussed in depth.

PMID- 20058267
TI  - The effects of local and systemic alendronate delivery on wear debris-induced
      osteolysis in vivo.
AB  - We investigated the effects of locally and systemically administered alendronate
      on wear debris-induced osteolysis in vivo. Endotoxin-free titanium particles were
      injected into rabbit femurs, prior to insertion of a nonweight-bearing
      polymethylmethacrylate plug into the distal femur canal. Then the particles were
      repeatedly injected into the knee 2, 4, and 6 weeks after the implantation.
      Alendronate was incorporated at three different concentrations (0.1, 0.5, and 1.0
      wt %) into bone cement for local delivery. For systemic delivery, alendronate was
      subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then
      once a week until sacrifice. Eight weeks postoperatively, there was significant
      evidence of osteolysis surrounding the plug in the control group compared with
      markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the
      systemic group. There was a concentration-dependent effect of alendronate-loaded
      bone cement on the improvement of peri-prosthetic bone stock. Notably, no
      significant differences were found between the 0.5 wt % and the systemic group in
      peri-prosthetic bone stock and implant fixation. Collectively, although the
      biological efficacy after the systemic delivery of alendronate was slightly
      higher than that in the local treatment groups, alendronate-loaded bone cement
      may be therapeutically effective in inhibiting titanium particle-induced
      osteolysis in vivo.

PMID- 20058268
TI  - Improved bioengineered cartilage tissue formation following cyclic compression is
      dependent on upregulation of MT1-MMP.
AB  - The generation of bioengineered cartilage tissue suitable for transplantation is
      a potential therapy to treat damaged cartilage. We have shown previously that the
      physical and biomechanical properties of bioengineered cartilage can be improved
      by the application of 30 min of cyclic compression by a mechanism involving
      sequential upregulation of gene and protein levels of membrane type-1 matrix
      metalloproteinase (MT1-MMP) and MMP-13. In the current study, we demonstrated
      that MT1-MMP is critical to this response, as blocking the upregulation of MT1
      MMP prevented the improvement in tissue formation. MT1-MMP seems to act by
      inducing tissue remodeling as evidenced by the presence of aggrecan degradation
      products by Western blot analysis and increased release of matrix molecules into
      the media. Release of these molecules was diminished when MT1-MMP upregulation
      was prevented. This matrix degradation was likely due to MT1-MMP, as under
      conditions where MMP-13 expression is maintained (stimulation in the presence of
      MT1-MMP siRNA) the release of these matrix molecules into the media was still
      prevented. It also appears that MT1-MMP does not regulate MMP-13 gene expression,
      as MT1-MMP-siRNA pretreatment had no effect on MMP-13 expression following
      mechanical stimulation. Further analysis of the anabolic genes and proteins
      involved in mechanically stimulated cartilage will lead to better understanding
      of the mechanism(s) underlying tissue formation yielding improved bioengineered
      cartilage.

PMID- 20058269
TI  - Effects of estrogen deficiency and low bone mineral density on healthy knee
      cartilage in rabbits.
AB  - The purpose of this study was to compare the effects of estrogen deficiency and
      bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy
      (OVX) was performed in 13 rabbits, 6 of which also received systemic
      glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as
      controls. Bone mineral density (BMD) was measured by dual X-ray absorptiometry in
      lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks
      after OVX. After sacrifice, the knees were dissected, macroscopy was assessed,
      and histological cartilage abnormalities were evaluated according to the Mankin
      score. Correlations of Mankin with BMD at different regions were also performed.
      When compared to baseline, differences in BMD were only found in spine and knee
      of the animals receiving glucocorticoids. All the animals subjected to OVX had a
      significantly higher Mankin score than controls. Mankin was upper in OVX animals
      receiving glucocorticoids, but differences were not significant. The Mankin score
      was inversely related with BMD in lumbar spine (r = -0.67; p < 0.01). Although
      low bone mineral density contributes to the minor osteoarthritic alterations
      observed in our model, estrogen deficiency itself seems to act directly to induce
      the main pathogenic effects in healthy cartilage of the rabbit.

PMID- 20058270
TI  - Fracture models in the lumbar sheep spine: a biomechanical investigation.
AB  - The purpose of this study was to find out if a limited resection of the cranial
      vertebral body leaving the posterior wall intact is a sufficient model for AO
      type 3 fractures, or if additional resection of the posterior wall is necessary.
      In six, fresh-frozen, lumbar sheep spine specimens, the segmental stability was
      tested in three motion planes in a spine tester. First, the intact specimens were
      tested. Then, partial resection of the intervertebral disc L3/4 and resection of
      the cranial vertebral body of L4 was performed, leaving the posterior wall
      intact. This defect was tested without instrumentation and with a ventral
      monosegmental interlocking plate mounted. Then, the defect was extended to a
      total cranial resection, including the posterior wall, and the tests were
      subsequently repeated. The stability of both types of defects under the different
      conditions was compared. Without instrumentation, the total cranial resection
      showed significantly more ROM in flexion/extension and axial rotation than
      partial cranial resection. With the ventral interlocking plate mounted, the
      instability in total cranial resection was significantly higher in
      flexion/extension, with the relative relation even being increased. In axial
      rotation and lateral bending, the differences were equalized by the mounted
      plate. From a biomechanical point of view, total cranial resection including the
      posterior wall should be preferred as a sheep spine fracture model for AO type 3
      fractures.

PMID- 20058271
TI  - Exercise following a short immobilization period is detrimental to tendon
      properties and joint mechanics in a rat rotator cuff injury model.
AB  - Rotator cuff tears are a common clinical problem that can result in pain and
      disability. Previous studies in a rat model showed enhanced tendon to bone
      healing with postoperative immobilization. The objective of this study was to
      determine the effect of postimmobilization activity level on insertion site
      properties and joint mechanics in a rat model. Our hypothesis was that exercise
      following a short period of immobilization will cause detrimental changes in
      insertion site properties compared to cage activity following the same period of
      immobilization, but that passive shoulder mechanics will not be affected. We
      detached and repaired the supraspinatus tendon of 22 Sprague-Dawley rats, and the
      injured shoulder was immobilized postoperatively for 2 weeks. Following
      immobilization, rats were prescribed cage activity or exercise for 12 weeks.
      Passive shoulder mechanics were determined, and following euthanasia, tendon
      cross-sectional area and mechanical properties were measured. Exercise following
      immobilization resulted in significant decreases compared to cage activity in
      range of motion, tendon stiffness, modulus, percent relaxation, and several
      parameters from both a structurally based elastic model and a quasi-linear
      viscoelastic model. Therefore, we conclude that after a short period of
      immobilization, increased activity is detrimental to both tendon mechanical
      properties and shoulder joint mechanics, presumably due to increased scar
      production.

PMID- 20058272
TI  - The influence of sequential debridement in total knee arthroplasty on the flexion
      axis of the knee using computer-aided navigation.
AB  - The effects of osteophyte debridement, bony cuts, and soft tissue releases on the
      functional flexion axis of the knee can be assessed by evaluating 3D kinematics
      following each step of a total knee arthroplasty. Using a navigated knee system
      with dedicated software, the functional flexion axis (helical axis) can be
      determined after each step. Five paired fresh-frozen cadaveric knees were used
      with a CT scan performed on each specimen identifying implanted fiducial markers.
      Kinematics data were recorded during each step of sequential osseous cuts and
      soft tissue releases for both an unloaded and loaded limb by each of three
      surgeons. The functional helical (flexion/extension) axis was identified for all
      specimens. The internal/external rotation angle (theta) of the helical axis
      differed from the transepicondylar axis by -8.3 degrees to +6.7 degrees for the
      unloaded condition. theta ranged from -7.2 degrees to +7.4 degrees with
      distraction. Soft tissue releases had no effect on theta; until a bony cut of the
      articular surface, which increased theta from -0.3 degrees to +9.7 degrees.
      Implantation of cruciate retaining prosthetic components subsequently reduced the
      theta range -7.3 degrees to +4.0 degrees. Thus, soft tissue releases had minimal
      effect on theta of the helical axis except for resection of the proximal tibia.
      Implantation of the CR prosthesis reduced e close to that of the intact knee. In
      a minority of knees, the helical axis did not coincide exactly with the
      transepicondylar axis. Interspecimen and left/right variability of theta were
      significant, although interinvestigator variability and an applied distraction
      force were insignificant.

PMID- 20058273
TI  - Chondrogenic differentiation and lubricin expression of caprine infraspinatus
      tendon cells.
AB  - Reparative strategies for the treatment of injuries to tendons, including those
      of the rotator cuff of the shoulder, need to address the formation of the
      cartilage which serves as the attachment apparatus to bone and which forms at
      regions undergoing compressive loading. Moreover, recent work indicates that
      cells employed for rotator cuff repair may need to synthesize a lubricating
      glycoprotein, lubricin, which has recently been found to play a role in tendon
      tribology. The objective of the present study was to investigate the chondrogenic
      differentiation and lubricin expression of caprine infraspinatus tendon cells in
      monolayer and three-dimensional culture, and to compare the behavior with bone
      marrow-derived mesenchymal stem cells (MSCs). The results demonstrated that while
      tendon cells in various media, including chondrogenic medium, expressed lubricin,
      virtually none of the MSCs synthesized this important lubricating molecule. Also
      of interest was that the cartilage formation capacity of the tendon cells grown
      in pellet culture in chondrogenic medium was comparable with MSCs. These data
      inform the use of tendon cells for rotator cuff repair, including for
      fibrocartilaginous zones.

PMID- 20058274
TI  - Bone marrow-derived mesenchymal stem cells express the pericyte marker 3G5 in
      culture and show enhanced chondrogenesis in hypoxic conditions.
AB  - Bone marrow-derived mesenchymal stem cells are a potential source of cells for
      the repair of articular cartilage defects. Hypoxia has been shown to improve
      chondrogenesis in some cells. In this study, bone marrow-derived stem cells were
      characterized and the effects of hypoxia on chondrogenesis investigated. Adherent
      bone marrow colony-forming cells were characterized for stem cell surface
      epitopes, and then cultured as cell aggregates in chondrogenic medium under
      normoxic (20% oxygen) or hypoxic (5% oxygen) conditions. The cells stained
      strongly for markers of adult mesenchymal stem cells, and a high number of cells
      were also positive for the pericyte marker 3G5. The cells showed a chondrogenic
      response in cell aggregate cultures and, in lowered oxygen, there was increased
      matrix accumulation of proteoglycan, but less cell proliferation. In hypoxia,
      there was increased expression of key transcription factor SOX6, and of collagens
      II and XI, and aggrecan. Pericytes are a candidate stem cell in many tissue, and
      our results show that bone marrow-derived mesenchymal stem cells express the
      pericyte marker 3G5. The response to chondrogenic culture in these cells was
      enhanced by lowered oxygen tension. This has important implications for tissue
      engineering applications of bone marrow-derived stem cells.

PMID- 20058275
TI  - Nano-scale topography of bearing surface in advanced alumina/zirconia hip joint
      before and after severe exposure in water vapor environment.
AB  - The aim of this study was to perform a surface morphology assessment with
      nanometer scale resolution on femoral heads made of an advanced zirconia
      toughened alumina (ZTA) composite. Femoral heads were characterized to a degree
      of statistical accuracy in the as-received state and after exposures up to 100 h
      in severe vapor-moist environment. Surface screening was made using an atomic
      force microscope (AFM). Scanning was systematically repeated on portions of
      surface as large as several tens of micrometers, randomly selected on the head
      surface, to achieve sufficient statistical reliability without lowering the
      nanometer-scale spatial resolution of the roughness measurement. No significant
      difference was found in the recorded values of surface roughness after
      environmental exposure (at 134 degrees C, under 2 bar), which was always
      comparable to that of the as-received head. Surface roughness safely lay <10 nm
      after environmental exposures up to 100 h, which corresponded to an exposure time
      in vivo of several human lifetimes (i.e., according to an experimentally derived
      thermal activation energy). In addition, the roughness results were significantly
      (about one order of magnitude) lower as compared to those recorded on femoral
      heads made of monolithic zirconia tested under the same conditions.

PMID- 20058276
TI  - Collagen scaffold supplementation does not improve the functional properties of
      the repaired anterior cruciate ligament.
AB  - Primary suture anterior cruciate ligament (ACL) repair was abandoned in favor of
      reconstruction due to a high rate of clinical failures. However, the insertion of
      a collagen scaffold loaded with platelets into the wound at the time of suture
      repair ("enhanced primary repair") has been shown to improve functional healing
      in animal models. Our objectives were to determine if using a collagen scaffold
      alone (without platelets) would be sufficient to increase the structural
      properties of the repaired ACL and decrease postoperative knee laxity compared to
      suture repair without the scaffold. Eight Yucatan minipigs underwent bilateral
      ACL transection and suture repair. In one knee, the repair was augmented with a
      collagen scaffold (SCAFFOLD group) while the other had suture alone (SUTURE
      group). After 13 weeks of healing, knee joint laxity and the structural
      properties of the ACL were measured. The addition of the collagen scaffold to
      suture repair of a transected ACL did not significantly improve the mean
      anteroposterior knee laxity [SCAFFOLD vs. SUTURE: 6.1 +/- 1.4 vs. 4.4 +/- 2.0 mm
      (p = 0.07), 8.1 +/- 2.0 vs. 7.6 +/- 2.0 mm (p = 0.66), and 6.2 +/- 1.2 vs. 6.1 +/
      1.8 mm (p = 0.85) at 30 degrees, 60 degrees, and 90 degrees flexion,
      respectively]. Likewise, there were no significant differences in the structural
      properties [SCAFFOLD vs. SUTURE: 367 +/- 185.9 vs. 322 +/- 122.0N (p = 0.66) and
      90.7 +/- 29.5 vs. 85.0 +/- 30.3N/mm (p = 0.74) for the yield load and linear
      stiffness, respectively]. The use of a collagen scaffold alone to enhance suture
      repair of the ACL was ineffective in this animal model. Future work will be
      directed at stimulating biological activity in the scaffold.

PMID- 20058277
TI  - Platelet-rich plasma impairs osteoclast generation from human precursors of
      peripheral blood.
AB  - Platelet-rich plasma is used to accelerate bone repair for the release of
      osteogenic growth factors from activated platelets. To date, the effects on
      osteoclasts have been only scarcely investigated, even though these cells are
      crucial for bone remodeling. The aim of this research was the evaluation of the
      effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human
      blood precursors. We evaluated both the ability to influence osteoclast
      differentiation induced by the receptor activator of nuclear factor-kappaB ligand
      (RANKL), and the ability to induce osteoclast differentiation without RANKL. In
      both assays, the incubation with PRP supernatant at 10% did not significantly
      affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive
      multinucleated cells that were able to form the F-actin ring. However, when PRP
      at 25 and 50% was added to the medium without RANKL, the generation of TRACP
      positive multinucleated cells was inhibited. PRP, even at 10%, reduced the
      osteoclast-mediated bone collagen degradation, suggesting inhibition of
      osteoclast activation. Similarly, after incubation with PRP supernatant,
      calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP
      at 10% interfered with the complete differentiation process of human osteoclast
      precursors. At higher concentration it impaired osteoclast formation also at an
      early stage of differentiation.

PMID- 20058278
TI  - Hyaluronan modulates cell proliferation and mRNA expression of adhesion-related
      procollagens and cytokines in glenohumeral synovial/capsular fibroblasts in
      adhesive capsulitis.
AB  - There is a growing body of evidence supporting the use of hyaluronan (HA) in
      patients with adhesive capsulitis of the shoulder, although the mechanisms of the
      effect have not yet been clarified. This in vitro study examined the effects of
      HA on glenohumeral synovial/capsular fibroblasts (GSCFs) from patients with
      adhesive capsulitis of the shoulder. The study subjects were seven patients with
      primary or secondary adhesive capsulitis of the shoulder (average age: 55 years;
      range: 42-65). Synovial/capsular specimens were obtained from the rotator
      interval of each patient during arthroscopy. Part of the tissue specimen was used
      for histological analysis. The remainder of the tissue was prepared for cell
      culture. Various concentrations of HA (0.0-4.0 mg/mL) were added to the monolayer
      cultured GSCFs from these patients. Histological analysis consistently
      demonstrated chronic nonspecific inflammation with synovial hyperplasia,
      proliferation of vessels and fibroblasts, and increased amount of extracellular
      matrix. Treatment with HA at various concentrations significantly and dose
      dependently inhibited cell proliferation and decreased the expression levels of
      mRNA for adhesion-related procollagens and cytokines. Pretreatment with OS/37 did
      not reverse the inhibitory effect of HA. These results suggest that HA modulates
      cell proliferation and expression of the mRNA of adhesion-related procollagens
      and cytokines in GSCFs, preventing the progression of adhesion formation in
      patients with adhesive capsulitis of the shoulder.

PMID- 20058279
TI  - Copper-catalysed ring opening of polycyclic meso-hydrazines with
      trialkylaluminium reagents and SimplePhos ligands.
AB  - meso-Hydrazines could be desymmetrised by ring-opening reactions by using various
      metal catalysts to form substituted cyclopentenes, which have a high synthetic
      potential. Herein, we report the asymmetric copper-catalysed ring opening of a
      range of polycyclic hydrazines with trialkylaluminium reagents and SimplePhos
      ligands with both high isolated yields and enantioselectivities of up to 95 %.

PMID- 20058280
TI  - Structure-directing forces in intercluster compounds of cationic [Ag(14)(C[triple
      bond]CtBu)(12)Cl](+) building blocks and polyoxometalates: long-range versus
      short-range bonding interactions.
AB  - Crystallization of [Ag(14)(C[triple bond]CtBu)(12)Cl][BF(4)] and different
      polyoxometalates in organic solvents yields a series of new intercluster
      compounds: [Ag(14)(C[triple bond]CtBu)(12)Cl(CH(3)CN)](2)[W(6)O(19)] (1),
      (nBu(4)N)[Ag(14)(C[triple bond]CtBu)(12)Cl(CH(3)CN)](2)[PW(12)O(40)] (2), and
      [Ag(14)(C[triple bond]CtBu)(12)Cl](2)[Ag(14)(C[triple
      bond]CtBu)(12)Cl(CH(3)CN)](2)[SiMo(12)O(40)] (3). Applying the same technique to
      a system starting from polymeric {[Ag(3)(C[triple bond]CtBu)(2)][BF(4)]0.6
      H(2)O}(n) and the polyoxometalate (nBu(4)N)(2)[W(6)O(19)] results in the
      formation of [Ag(14)(C[triple bond]CtBu)(12)(CH(3)CN)(2)][W(6)O(19)] (4). Here,
      the Ag(14) cluster is generated from polymeric {[Ag(3)(C[triple
      bond]CtBu)(2)][BF(4)]0.6 H(2)O}(n) during crystallization. In a similar way,
      [Ag(15)(C[triple bond]CtBu)(12)(CH(3)CN)(5)][PW(12)O(40)] (5) has been obtained
      from {[Ag(3)(C[triple bond]CtBu)(2)][BF(4)]0.6 H(2)O}(n) and
      (nBu(4)N)(3)[PW(12)O(40)]. The use of charged building blocks was intentional,
      because at these conditions the contribution of long-range Coulomb interactions
      would benefit most from full periodicity of the intercluster compound, thus
      favoring formation of well-crystalline materials. The latter has been achieved,
      indeed. However, as a most conspicuous feature, equally charged species
      aggregate, which demonstrates that the short-range interactions between the
      "surfaces" of the clusters represent the more powerful structure direction forces
      than the long-range Coulomb bonding. This observation is of significant
      importance for understanding the mechanisms underlying self-organization of
      monodisperse and structurally well-defined particles of nanometer size.

PMID- 20058281
TI  - A computational study of the olefin epoxidation mechanism catalyzed by
      cyclopentadienyloxidomolybdenum(VI) complexes.
AB  - A DFT analysis of the epoxidation of C(2)H(4) by H(2)O(2) and MeOOH (as models of
      tert-butylhydroperoxide, TBHP) catalyzed by [Cp*MoO(2)Cl] (1) in CHCl(3) and by
      [Cp*MoO(2)(H(2)O)](+) in water is presented (Cp*=pentamethylcyclopentadienyl).
      The calculations were performed both in the gas phase and in solution with the
      use of the conductor-like polarizable continuum model (CPCM). A low-energy
      pathway has been identified, which starts with the activation of ROOH (R=H or Me)
      to form a hydro/alkylperoxido derivative, [Cp*MoO(OH)(OOR)Cl] or
      [Cp*MoO(OH)(OOR)](+) with barriers of 24.9 (26.5) and 28.7 (29.2) kcal mol(-1)
      for H(2)O(2) (MeOOH), respectively, in solution. The latter barrier, however, is
      reduced to only 1.0 (1.6) kcal mol(-1) when one additional water molecule is
      explicitly included in the calculations. The hydro/alkylperoxido ligand in these
      intermediates is eta(2)-coordinated, with a significant interaction between the
      Mo center and the O(beta) atom. The subsequent step is a nucleophilic attack of
      the ethylene molecule on the activated O(alpha) atom, requiring 13.9 (17.8) and
      16.1 (17.7) kcal mol(-1) in solution, respectively. The corresponding
      transformation, catalyzed by the peroxido complex [Cp*MoO(O(2))Cl] in CHCl(3),
      requires higher barriers for both steps (ROOH activation: 34.3 (35.2) kcal mol(
      1); O atom transfer: 28.5 (30.3) kcal mol(-1)), which is attributed to both
      greater steric crowding and to the greater electron density on the metal atom.

PMID- 20058282
TI  - Metal-catalyzed alpha-arylation of carbonyl and related molecules: novel trends
      in C-C bond formation by C-H bond functionalization.
AB  - Alpha-arylated carbonyl compounds are commonly occurring motifs in biologically
      interesting molecules and are therefore of high interest to the pharmaceutical
      industry. Conventional procedures for their synthesis often result in
      complications in scale-up, such as the use of stoichiometric amounts of toxic
      reagents and harsh reaction conditions. Over the last decade, significant efforts
      have been directed towards the development of metal-catalyzed alpha-arylations of
      carbonyl compounds as an alternative synthetic approach that operates under
      milder conditions. This Review summarizes the developments in this area to date,
      with a focus on how the substrate scope has been expanded through selection of
      the most appropriate synthetic method, such as the careful choice of ligands,
      precatalysts, bases, and reaction conditions.

PMID- 20058283
TI  - Serendipitous discovery of the catalytic hydroammoniumation and methylamination
      of alkynes.

PMID- 20058284
TI  - Binding and activation of N2O at transition-metal centers: recent mechanistic
      insights.
AB  - No laughing matter, nitrous oxide's role in stratospheric ozone depletion and as
      a greenhouse gas has stimulated great interest in developing and understanding
      its decomposition, particularly through the use of transition-metal promoters.
      Recent advances in our understanding of the reaction pathways for N(2)O reduction
      by metal ions in the gas phase and in heterogeneous, homogeneous, and biological
      catalytic systems have provided provocative ideas about the structure and
      properties of metal N(2)O adducts and derived intermediates. These ideas are
      likely to inform efforts to design more effective catalysts for N(2)O
      remediation.

PMID- 20058285
TI  - Hierarchical self-assembly of a chiral metal-organic framework displaying
      pronounced porosity.

PMID- 20058286
TI  - Assembly of substituted phenothiazines by a sequentially controlled CuI/ L
      proline-catalyzed cascade C-S and C-N bond formation.

PMID- 20058287
TI  - Analytical expressions for quantitative scanning electrochemical microscopy
      (SECM).
AB  - Scanning electrochemical microscopy (SECM), is a recent analytical technique in
      electrochemistry, which was developed in the 1990s and uses microelectrodes to
      probe various surfaces. Even with the well-known disc microelectrodes, the system
      geometry is not as simple as in regular electrochemistry. As a consequence even
      the simplest experiments, the so-called positive and negative feedback approach
      curves, cannot be described with exact analytical expressions. This review
      gathers all the analytical expressions available in the SECM literature in steady
      state feedback experiments. Some of them are claimed as general expressions,
      other are presented as approximate. Their validity is discussed in the light of
      the current understanding and computer facilities.

PMID- 20058288
TI  - 2D TR-NOESY experiments interrogate and rank ligand-receptor interactions in
      living human cancer cells.

PMID- 20058289
TI  - Preparation of photoluminescent nanorings with controllable bioreducibility and
      stimuli-responsiveness.

PMID- 20058290
TI  - Step-mediated anisotropic adsorption and condensation of tert-butylamine on
      Cu(111).
AB  - Scanning tunneling microscopy (STM) combined with density functional theory (DFT)
      calculations were applied in studying the anisotropic adsorption and condensation
      of tert-butylamine (t-BA) molecules in the vicinity of the steps on the Cu(111)
      surface. The preferential adsorption at the upper step edges and uneven
      distribution of t-BA in the vicinity of the steps illustrate the asymmetric
      electronic structure of the surface steps. Our observation demonstrates that the
      adsorption and diffusion of a polar molecule would be significantly mediated by
      steps on metal surfaces due to the molecule-step interaction and the
      intermolecular interactions.

PMID- 20058291
TI  - Graphene on Au(111): a highly conductive material with excellent adsorption
      properties for high-resolution bio/nanodetection and identification.
AB  - Based on numerical simulations and experimental studies, we show that a composite
      material which consists of a sheet of graphene on a Au(111) surface exhibits both
      an excellent conductivity and the ability to stably adsorb biomolecules. If we
      use this material as a substrate, the signal-to-noise ratios can be greatly
      enhanced. The key to this unique property is that graphene can stably adsorb
      carbon-based rings, which are widely present in biomolecules, due to pi-stacking
      interactions while the substrate retains the excellent conductivity of gold.
      Remarkably, the signal-to-noise ratio is found to be so high that the signal is
      clearly distinguishable for different nucleobases when an ssDNA is placed on this
      graphene-on-Au(111) material. Our finding opens opportunities for a range of
      bio/nano-applications including single-DNA-molecule-based biodevices and
      biosensors, particularly, high-accuracy sequencing of DNA strands with repeating
      segments.

PMID- 20058292
TI  - Monooxime-monocarbamoyl Bispyridinium Xylene-Linked Reactivators of
      Acetylcholinesterase-Synthesis, In vitro and Toxicity Evaluation, and Docking
      Studies.
AB  - Acetylcholinesterase (AChE) reactivators are crucial antidotes to organophosphate
      intoxication. A new series of 26 monooxime-monocarbamoyl xylene-linked
      bispyridinium compounds was prepared and tested in vitro, along with known
      reactivators (pralidoxime, HI-6, obidoxime, trimedoxime, methoxime, K107, K108
      and K203), on a model of tabun- and paraoxon-, methylparaoxon- and DFP-inhibited
      human erythrocyte AChE. Although their ability to reactivate tabun-inhibited AChE
      did not exceed that of the previously known compounds, some newly prepared
      compounds showed promising reactivation of pesticide-inhibited AChE. The acute
      toxicity of the novel compounds was also determined. Docking studies using tabun
      inhibited AChE were performed for three compounds of interest. The structure
      activity relationship (SAR) study confirmed the apparent influence of the xylene
      linkage and carbamoyl moiety on the reactivation ability and toxicity of the
      agents.

PMID- 20058293
TI  - Chelator fragment libraries for targeting metalloproteinases.

PMID- 20058294
TI  - Composites of molecular-anchored graphene and nanotubes with multitubular
      structure: a new type of carbon electrode.
AB  - Graphene-carbon nanotube nanocomposites that contain multitubular co-axial and
      hollow cavity microstructures are prepared. Nanometer-scale graphene sheets are
      anchored with oxalic acid and consequently linked to each other via oxalyl
      bonding, thereby self-assembling into numerous outer tubes with distinct borders
      and a homogeneous thickness along the innermost pristine tube, which acts as a
      template. The resulting interstitial inclusion of oxalic acid into the graphene
      stacking modifies both the surface and the bulk properties of the newly formed
      tubes. It is observed that the unique microstructure of the modified graphene
      carbon nanotube nanocomposite significantly facilitates the insertion and
      extraction of lithium, demonstrating superior electrochemical performance as
      anodes for lithium-based batteries. This facile chemical approach provides a new
      graphene architecture, showing superior stability, for use as anode material in
      lithium ion batteries.

PMID- 20058295
TI  - Size dimorphism and avian-perceived sexual dichromatism in a New Zealand endemic
      bird, the whitehead Mohoua albicilla.
AB  - Sex differences in behavior, morphology, and physiology are common in animals. In
      many bird species, differences in the feather colors of the sexes are apparent
      when judged by human observers and using physical measures of plumage
      reflectance, cryptic (to human) plumage dichromatism has also been detected in
      several additional avian lineages. However, it remains to be confirmed in almost
      all species whether sexual dichromatism is perceivable by individuals of the
      studied species. This latter step is essential because it allows the evaluation
      of alternative hypotheses regarding the signaling and communication functions of
      plumage variation. We applied perceptual modeling of the avian visual system for
      the first time to an endemic New Zealand bird to provide evidence of subtle but
      consistent sexual dichromatism in the whitehead, Mohoua albicilla. Molecular
      sexing techniques were also used in this species to confirm the extent of the
      sexual size dimorphism in plumage and body mass. Despite the small sample sizes,
      we now validate previous reports based on human perception that in male
      whiteheads head and chest feathers are physically brighter than in females. We
      further suggest that the extent of sexual plumage dichromatism is pronounced and
      can be perceived by these birds. In contrast, although sexual dimorphism was also
      detectable in the mass among the DNA-sexed individuals, it was found to be less
      extensive than previously thought. Sexual size dimorphism and intraspecifically
      perceivable plumage dichromatism represent reliable traits that differ between
      female and male whiteheads. These traits, in turn, may contribute to honest
      communication displays within the complex social recognition systems of
      communally breeding whitehead and other group-breeding taxa.

PMID- 20058296
TI  - A comparison of the external morphology of the membranous inner ear in
      elasmobranchs.
AB  - Studies on the elasmobranch inner ear have focused predominantly on a small group
      of sharks, particularly, carcharhinids. As a result, subsequent studies in other
      species have subdivided species into two main groups: those typical and those
      atypical of carcharhinid sharks. This study proposes a different set of inner-ear
      morphology groupings to those previously suggested. The inner ears from 17
      species of elasmobranchs (representing both sharks and rays) are examined in this
      study and based on morphometric data some groups include both rays and sharks.
      Four groups are now proposed based predominantly on the shape and dimensions of
      the membranous otoconial organs, and characteristics of the semicircular canals.
      Evident morphological differences between the ear types belonging to the new
      groups include the membranes of the semicircular canals being bound to the
      otoconial organs in some species, while only being connected via the canal ducts
      in others, as well as clear variation present in saccular organ size. Previous
      studies examining variation in the inner ear have attributed differences to
      either phylogeny or functional significance. Results from this study suggest that
      neither phylogeny nor feeding strategy solely accounts for the morphological
      diversity present in the external morphology of the elasmobranch inner ear.

PMID- 20058297
TI  - Polypropylene background traction device for microvascular anastomosis.

PMID- 20058298
TI  - The variability of the Superficial Inferior Epigastric Artery (SIEA) and its
      angiosome: A clinical anatomical study.
AB  - INTRODUCTION: The superficial inferior epigastric artery (SIEA) is a useful
      pedicle in supply to the lower abdominal integument, with its use sparing damage
      to rectus abdominis muscle or sheath. However, it is limited in usefulness due to
      its anatomical variability. While previous anatomical studies have been limited
      in number and study design, the use of preoperative imaging has enabled the
      analysis of this vasculature in large numbers and greater anatomical detail.
      METHODS: A clinical anatomical study of 500 hemi-abdominal walls in 250
      consecutive patients undergoing preoperative computed tomographic angiography
      (CTA) prior to autologous breast reconstruction was undertaken. The presence,
      size, location, and branching pattern of the SIEA were assessed in each case.
      RESULTS: The SIEA was identified in 468 cases, an incidence of 94%. Its mean
      diameter was 0.6 mm, and in 24% of cases was of a diameter >1.5 mm. SIEA location
      was highly variable, with mean position 2-cm lateral to the linea semilunaris
      (range 0-8 cm lateral), and relationship to the superficial inferior epigastric
      vein (SIEV) was also highly variable, with the distance between them ranging from
      0.3 to 8.5 cm apart. SIEA branches directly crossed the abdominal midline in 5%
      of cases. Larger SIEA diameters correlated with a decrease in diameter of
      ipsilateral DIEA perforators. CONCLUSION: The SIEA is present more frequently
      than previously demonstrated, but is typically too small for use in free tissue
      transfer. The variable degree of SIEA branching suggests that its territory of
      supply is also variable, and that preoperative imaging may be useful in planning
      SIEA flaps.

PMID- 20058299
TI  - Portable duplex ultrasonography: A diagnostic and decision-making tool in
      reconstructive microsurgery.
AB  - Unidirectional Doppler is a common diagnostic tool by the Reconstructive
      Microsurgeons; however, it may generate false signals and surely provides less
      imaging data as compared to duplex ultrasonography. We have reviewed the use of
      Portable Duplex Ultrasonography (PDU) in 16 patients who underwent complex soft
      tissue/bone reconstruction, aiming to determine its role in the design and
      management of free tissue transfer. According to our data, there were
      modifications either of the surgical plan and/or of patient's management, based
      on PDU findings, in 10 out of 16 patients (62.5%). The use of ultrasound directed
      to subtle modifications in three patients (19%), but to significant changes of
      the surgical plan in four patients (25%). Also, the use of ultrasound improved
      significantly the postoperative management in three patients (19%). Thus,
      significant impact of PDU in patient's treatment was recorded in 44% of cases.
      Portable ultrasound represents generally available method for preoperative,
      intraoperative, and postoperative diagnosis and decision-making in free tissue
      transfer, hence could replace in the near future the unidirectional Doppler in
      the hands of Microsurgeons.

PMID- 20058300
TI  - Backup perforator flap derived from a previously transferred musculocutaneous
      free flap.
AB  - INTRODUCTION: Reconstruction of the lower leg commonly requires a free tissue
      transfer after Gustillo grade IIIB-IIIC injuries and severe postoncological
      resections, where, free musculocutaneous flaps (MCF) are preferred for their size
      and robust blood supply. The anastomoses are performed at more proximal levels to
      keep them away from the trauma zone. This reasonable maneuver causes the distal
      of the flap to cover the most critical part of the defect. Any marginal necrosis,
      then, ends in exposure of the bone or implant. Reported here is the use of a
      perforator flap derived from a previously transferred free MCF as a backup
      tissue. PATIENTS AND METHODS: Distal marginal necrosis exposing vital structures
      were encountered after six free MCF transfers during the last 6 years. These were
      highly complicated cases in which no regional flap options were available and a
      second free flap was unfeasible due to recipient vessel problems. A perforator
      flap was elevated on the perforator vessel(s) penetrating the underlying muscle
      of the previous MCF and either advanced or transposed to cover the defect. Donor
      sites on MCF were closed primarily. RESULTS: Wound dehiscence that healed
      secondarily was observed in two cases. The knee prosthesis was removed in one
      case due to uncontrolled osteomyelitis. No complications were detected in other
      three cases. CONCLUSION: The described flap can be a leg saver whenever a
      previously transferred free MCF fails to cover the distal site of the defect. The
      flap can be advanced for 3-5 cm and allows more than 90 degrees of rotation.

PMID- 20058301
TI  - Reorganization in motor cortex after brachial plexus avulsion injury and repair
      with the contralateral C7 root transfer in rats.
AB  - The purpose of our study was to establish the profile of cortical reorganization
      in whole BPAI on rats and evaluate changes of cortical reorganization after
      repair of the median nerve with the contralateral C7 root transfer. Forty adult
      SD rats underwent whole roots avulsion of left brachial plexus, among them 20
      received contralateral C7 root transfer to the injured median nerve.
      Intracortical microstimulation was performed in primary motor cortex (M1) at
      intervals of 3, 5, 7, and 10 months, postoperatively. The maps of motor cortical
      responses were constructed. Five normal rats were used as the control. Results
      showed that stimulating right M1 elicited motion of left vibrissae, submaxilla,
      neck, back, and left hindlimb after left BPAI, among them neck representation
      area replaced the forelimb area throughout the reorganization process. The left
      forelimb representation area was found in the left motor cortex 5 months after
      the contralateral C7 root transfer and existed in both motor cortexes at 7th
      postoperative month. The left forelimb representation area was detected only in
      right motor cortex at 10th month, postoperatively. In conclusions, after the
      contralateral C7 root transfer for repair of the median nerve in BPAI, the
      cortical reorganization occurred in a time-dependent reorganization. The findings
      from this study demonstrate that brain involves in the functional recovery after
      BPAI and repair with nerve transfer and suggest that efforts to improve the
      results from nerve repair should address the peripheral nerve as well as the
      brain.

PMID- 20058302
TI  - Amino acid metabolism of bovine blastocysts: a biomarker of sex and viability.
AB  - The ratio of male/female embryos may be modified by environmental factors such as
      maternal diet in vivo and the composition of embryo culture media in vitro. We
      have used amino acid profiling, a noninvasive marker of developmental potential
      to compare the effect of sex on the metabolism of bovine blastocysts conceived in
      vivo and in vitro. Blastocysts were incubated individually for 24 hr in a close
      to-physiological mixture of amino acids and the depletion or appearance of 18
      amino acids measured using HPLC. Blastocysts were then sexed by PCR. Amino acid
      depletion by in vitro-produced blastocysts and expanded blastocysts was higher
      than in embryos conceived in vivo (P = 0.02). When cultured in vitro, female
      embryos exhibited increased depletion of arginine, glutamate, and methionine and
      appearance of glycine, while male embryos displayed increased depletion of
      phenylalanine, tyrosine, and valine. Overall, in vitro-produced blastocysts
      exhibited sex-specific differences in metabolic profiles of 7 out of 18 amino
      acids; in vivo-produced, in 2 out of 18. These differences had disappeared by the
      expanded blastocyst stages. We have also shown that amino acid metabolism can
      predict the ability of bovine zygotes to develop to the blastocyst stage,
      providing "proof of principle" for the use of this technology in clinical IVF to
      select single embryos for transfer and thereby avoid the problem of multiple
      births.

PMID- 20058306
TI  - Fine-needle aspiration cytology of scar endometriosis: study of seven cases and
      literature review.
AB  - Endometriosis is defined as the presence of endometrial-like glands and stroma
      outside the uterine endometrial lining. Endometrial tissue has also been
      identified in numerous surgical or procedure scars, including cesarean section
      and laparoscopic trocar tract. A prospective study was conducted at Maternidade
      Escola Assis Chateaubriand, Faculty of Medicine, Federal University of Ceara,
      Brazil in seven patients with abdominal wall mass pathologically proven as scar
      endometriosis from January 2004 to December 2008. All cases were submitted to
      fine-needle aspiration cytology (FNAC). Age ranged from 21 to 42 years old (mean:
      30) with parity ranging from 0 to 3 (mean: 1.4). The preceding history of pelvic
      procedures was miomectomy (1 of 7), cesarean section (3 of 7), and diagnostic
      laparoscopy (3 of 7). The complaints occurred about 18 months after the surgical
      proceeding. The FNAC findings were endometrial-like epithelial cells (6 of 7) and
      stromal cells (6 of 7); decidualization occurred in 2 of 7 cases. Hemosiderin
      laden macrophages were present in all cases. FNAC is a fast and accurate method
      to make the diagnosis before the surgery, avoiding errors in the approach of the
      abdominal wall endometriosis' scars.

PMID- 20058304
TI  - Chronic expression of PPAR-delta by oligodendrocyte lineage cells in the injured
      rat spinal cord.
AB  - The transcription factor peroxisome proliferator-activated receptor (PPAR)-delta
      promotes oligodendrocyte differentiation and myelin formation in vitro and is
      prevalent throughout the brain and spinal cord. Its expression after injury,
      however, has not been examined. Thus, we used a spinal contusion model to examine
      the spatiotemporal expression of PPAR-delta in naive and injured spinal cords
      from adult rats. As previously reported, PPAR-delta was expressed by neurons and
      oligodendrocytes in uninjured spinal cords; PPAR-delta was also detected in NG2
      cells (potential oligodendrocyte progenitors) within the white matter and gray
      matter. After spinal cord injury (SCI), PPAR-delta mRNA and protein were present
      early and increased over time. Overall PPAR-delta+ cell numbers declined at 1 day
      post injury (dpi), likely reflecting neuron loss, and then rose through 14 dpi. A
      large proportion of NG2 cells expressed PPAR-delta after SCI, especially along
      lesion borders. PPAR-delta+ NG2 cell numbers were significantly higher than naive
      by 7 dpi and remained elevated through at least 28 dpi. PPAR-delta+
      oligodendrocyte numbers declined at 1 dpi and then increased over time such that
      >20% of oligodendrocytes expressed PPAR-delta after SCI compared with
      approximately 10% in uninjured tissue. The most prominent increase in PPAR-delta+
      oligodendrocytes was along lesion borders where at least a portion of newly
      generated oligodendrocytes (bromodeoxyuridine+) were PPAR-delta+. Consistent with
      its role in cellular differentiation, the early rise in PPAR-delta+ NG2 cells
      followed by an increase in new PPAR-delta+ oligodendrocytes suggests that this
      transcription factor may be involved in the robust oligodendrogenesis detected
      previously along SCI lesion borders.

PMID- 20058307
TI  - Proximal-type epithelioid sarcoma of the maxilla with metastasis to the scalp:
      Cytologic findings of an unusual malignant tumor.
AB  - Epithelioid sarcoma of proximal type (ESPT), a subtype of epithelioid sarcoma, is
      an uncommon malignant neoplasm of the soft tissue with histo- and cytologic
      features similar to epithelioid sarcoma, classic type and to the more commonly
      encountered extra-renal malignant rhabdoid tumor (EMRT). Unlike classic
      epithelioid sarcoma, ESPT usually involves pelvic, perineal, and genital regions
      and has an aggressive clinical course. Like EMRT, ESPT can have aberrations of
      the INI1 gene on chromosome 22q, which results in the loss of INI1 protein
      expression. We describe here the cytological findings of an ESPT metastatic to
      the scalp in a 14-year-old boy. Cytological preparations showed a discohesive
      population of pleomorphic ovoid to polygonal cells with large irregular nuclei
      and prominent nucleoli. Isolated cells with rhabdoid features were noted. These
      cells had abundant cytoplasm and occasional intracytoplasmic hyaline inclusions.
      In the light of the patient's clinical history of a known primary ESPT of the
      maxilla, the cytologic features were distinct enough to render a diagnosis of a
      metastatic lesion to the skull.

PMID- 20058308
TI  - A novel model of retinal ablation demonstrates that the extent of rod cell death
      regulates the origin of the regenerated zebrafish rod photoreceptors.
AB  - The adult zebrafish retina continuously produces rod photoreceptors from
      infrequent Muller glial cell division, yielding neuronal progenitor cells that
      migrate to the outer nuclear layer and become rod precursor cells that are
      committed to differentiate into rods. Retinal damage models suggested that rod
      cell death induces regeneration from rod precursor cells, whereas loss of any
      other retinal neurons activates Muller glia proliferation to produce pluripotent
      neuronal progenitors that can generate any other neuronal cell type in the
      retina. We tested this hypothesis by creating two transgenic lines that expressed
      the E. coli nitroreductase enzyme fused to EGFP (NTR-EGFP) in only rods. Treating
      transgenic adults with metronidazole resulted in two rod cell death models.
      First, killing all rods throughout the Tg(zop:nfsB-EGFP)(nt19) retina induced
      robust Muller glial proliferation, which yielded clusters of neuronal progenitor
      cells. In contrast, ablating only a subset of rods across the Tg(zop:nfsB
      EGFP)(nt20) retina led to rod precursor, but not Muller glial, cell
      proliferation. We propose that two different criteria determine whether rod cell
      death will induce a regenerative response from the Muller glia rather than from
      the resident rod precursor cells in the ONL. First, there must be a large amount
      of rod cell death to initiate Muller glia proliferation. Second, the rod cell
      death must be acute, rather than chronic, to stimulate regeneration from the
      Muller glia. This suggests that the zebrafish retina possesses mechanisms to
      quantify the amount and timing of rod cell death.

PMID- 20058309
TI  - Localization of a GABA transporter to glial cells in the developing and adult
      olfactory pathway of the moth Manduca sexta.
AB  - Glial cells have several critical roles in the developing and adult olfactory
      (antennal) lobe of the moth Manduca sexta. Early in development, glial cells
      occupy discrete regions of the developing olfactory pathway and processes of
      gamma-aminobutyric acid (GABA)ergic neurons extend into some of these regions.
      Because GABA is known to have developmental effects in a variety of systems, we
      explored the possibility that the glial cells express a GABA transporter that
      could regulate GABA levels to which olfactory neurons and glial cells are
      exposed. By using an antibody raised against a characterized high-affinity M.
      sexta GABA transporter with high sequence homology to known mammalian GABA
      transporters (Mbungu et al. [1995] Arch. Biochem. Biophys. 318:489-497; Umesh and
      Gill [2002] J. Comp. Neurol. 448:388-398), we found that the GABA transporter is
      localized to subsets of centrally derived glial cells during metamorphic adult
      development. The transporter persists into adulthood in a subset of the neuropil
      associated glial cells, but its distribution pattern as determined by light-and
      electron-microscopic-level immunocytochemistry indicates that it could not serve
      to regulate GABA concentration in the synaptic cleft. Instead, its role is more
      likely to regulate extracellular GABA levels within the glomerular neuropil.
      Expression in the sorting zone glial cells disappears after the period of
      olfactory receptor axon ingrowth, but may be important during ingrowth if GABA
      regulates axon growth. Glial cells take up GABA, and that uptake can be blocked
      by L-2,4-diaminobutyric acid (DABA). This is the first molecular evidence that
      the central glial cell population in this pathway is heterogeneous.

PMID- 20058311
TI  - Phylotypic expression of the bHLH genes Neurogenin2, Neurod, and Mash1 in the
      mouse embryonic forebrain.
AB  - In the anamniote model animals, zebrafish and Xenopus laevis, highly comparable
      early forebrain expression patterns of proneural basic helix-loop-helix (bHLH)
      genes relevant for neurogenesis (atonal homologs, i.e., neurogenins/NeuroD and
      achaete-scute homologs, i.e., Ascl/ash) were previously revealed during a
      particular period of development (zebrafish: 3 days; frog: stage 48).
      Neurogenins/NeuroD on the one hand and Ascl1/ash1 on the other hand exhibit
      essentially mutually exclusive spatial patterns, probably reflecting different
      positional information received within the neural tube, and appear to underlie
      glutamatergic versus GABAergic neuronal differentiation, respectively.
      Significant data suggest that similar complementary localizations of these
      proneural genes and corresponding differentiation pathways also exist in the
      mouse, the prominent mammalian model. The present article reports on detailed
      mouse brain bHLH gene expression patterns to fill existing gaps in the
      identification of expression domains, especially outside the telencephalon.
      Clearly, there are strong similarities in the complementarity of territories
      expressing Ascl1/Mash 1 versus neurogenins/NeuroD in the entire mouse forebrain,
      except for the pretectal alar plate and basal plate of prosomeres 1-3. The
      analysis substantiates localization of neurogenins/NeuroD in the pallium,
      eminentia thalami, and dorsal thalamus, and expression of Ascl1/Mash 1 in the
      striatal and septal subpallium, preoptic region, ventral thalamus, and
      hypothalamus, which is highly similar to the situation described in Xenopus and
      zebrafish. Thus, all three vertebrate model species display a "phylotypic stage
      or period" corresponding to a temporally and spatially defined control of
      neurogenesis during forebrain development, ultimately resulting in the
      differentiation of distinct populations of glutamatergic versus GABAergic
      neurons.

PMID- 20058310
TI  - The cortistatin gene PSS2 rather than the somatostatin gene PSS1 is strongly
      expressed in developing avian autonomic neurons.
AB  - Somatostatin and cortistatin are neuromodulators with divergent expression
      patterns and biological roles. Whereas expression and function of genes encoding
      somatostatin (PSS1) and the related peptide cortistatin (PSS2) have been studied
      in detail for the central nervous system (CNS) and immune system, relatively
      little is known about their expression patterns in the peripheral nervous system
      (PNS). We compare the expression patterns of PSS1 and PSS2 in chicken embryos. At
      E14, PSS1 is higher in the CNS versus PNS, whereas PSS2 is higher in the PNS.
      During early development, PSS1 is transiently expressed in lumbar sympathetic
      ganglia and is detectable at low levels throughout the development of dorsal root
      and ciliary ganglia. In contrast, PSS2 expression increases as development
      progresses in sympathetic and dorsal root ganglia, whereas levels in ciliary
      ganglia by E8 are more than 100-fold higher than in sympathetic ganglia. Activin,
      which induces somatostatin-like immunoreactivity in ciliary ganglion neurons in
      vivo and in vitro, controls PSS2 expression by stabilizing PSS2 but not PSS1
      mRNA. We conclude that much of the somatostatin-like immunoreactivity in the
      developing avian peripheral nervous system is actually cortistatin, the PSS2
      product, as opposed to true somatostatin, which is the PSS1 product. The
      identification of PSS2 as the predominantly expressed somatostatin gene family
      member in avian autonomic neurons provides a molecular basis for further
      functional and pharmacological studies.

PMID- 20058312
TI  - The c-Rel subunit of nuclear factor-kappaB regulates murine liver inflammation,
      wound-healing, and hepatocyte proliferation.
AB  - In this study, we determined the role of the nuclear factor-kappaB (NF-kappaB)
      subunit c-Rel in liver injury and regeneration. In response to toxic injury of
      the liver, c-Rel null (c-rel(-/-)) mice displayed a defect in the neutrophilic
      inflammatory response, associated with impaired induction of RANTES (Regulated
      upon Activation, Normal T-cell Expressed, and Secreted; also known as CCL5). The
      subsequent fibrogenic/wound-healing response to both chronic carbon tetrachloride
      and bile duct ligation induced injury was also impaired and this was associated
      with deficiencies in the expression of fibrogenic genes, collagen I and alpha
      smooth muscle actin, by hepatic stellate cells. We additionally report that c-Rel
      is required for the normal proliferative regeneration of hepatocytes in response
      to toxic injury and partial hepatectomy. Absence of c-Rel was associated with
      blunted and delayed induction of forkhead box M1 (FoxM1) and its downstream
      targets cyclin B1 and Cdc25C. Furthermore, isolated c-rel(-/-) hepatocytes
      expressed reduced levels of FoxM1 and a reduced rate of basal and epidermal
      growth factor-induced DNA synthesis. Chromatin immunoprecipitation revealed that
      c-Rel binding to the FoxM1 promoter is induced in the regenerating liver.
      CONCLUSION: c-Rel has multiple functions in the control of liver homeostasis and
      regeneration and is a transcriptional regulator of FoxM1 and compensatory
      hepatocyte proliferation.

PMID- 20058313
TI  - Parotidotomy approach for a midcheek mass: a new surgical strategy.
AB  - OBJECTIVES/HYPOTHESIS: To report the feasibility and the results of a new
      surgical strategy for midcheek masses we called the parotidotomy approach. STUDY
      DESIGN: Retrospective consecutive case series. METHODS: Characteristics, surgical
      outcome, and cosmetic result of cases managed using the parotidotomy approach
      were collected by retrospectively reviewing medical records. The standard
      superficial parotidectomy approach was modified to dissect facial nerve branches
      selectively to obtain a symmetric facial contour. The parotid gland was fully
      bisected along the course of the zygomatic and buccal branches of the facial
      nerve to provide access to the midcheek mass. The bisected parotid gland was
      repositioned after mass excision. RESULTS: Seven patients (3 males and 4 females)
      were included in this study. The parotidotomy approach was accomplished in two
      cases with a malignant tumor (one acinic cell carcinoma, one low-grade
      mucoepidermoid carcinoma), four with a benign tumor (two pleomorphic adenoma, one
      basal cell adenoma, one facial nerve schwannoma), and in one case with a chronic
      inflammatory lesion (chronic sialadenitis). In no case was facial nerve paralysis
      or Frey's syndrome noticed after this approach. For the two malignant tumors,
      there was no evidence of recurrence or metastasis at 2-year and 2.5-year follow
      ups. Six of the seven patients were fully satisfied with the cosmetic results of
      surgery. The remaining patient had a mild sunken deformity of the midcheek where
      the mass had been located. CONCLUSIONS: To manage midcheek masses we modified the
      standard parotidectomy approach. This new surgical strategy, which we named the
      parotidotomy approach, provides surgically safe and cosmetically excellent
      results for midcheek masses.

PMID- 20058314
TI  - Spray cryotherapy for the treatment of glottic and subglottic stenosis.
AB  - OBJECTIVES/HYPOTHESIS: Functional partial occlusion of the glottic and subglottic
      areas by stenosis and strictures is challenging to manage despite a variety of
      surgical and endoluminal approaches that are prone to complications and
      inconsistent outcomes. We report here the first three human cases of glottic and
      subglottic narrowing treated with spray cryotherapy alone or in combination with
      balloon dilation. STUDY DESIGN: Institutional review board-approved clinical
      human trial. METHODS: A 42-year-old female with idiopathic subglottic strictures,
      a 74-year-old female with glottic strictures and vocal cord stenosis following
      neck radiation, and a 33-year-old female with strictures from a previous tracheal
      stent were treated by four cycles of a 5-second cryotherapy spray alone or with
      balloon dilation. The effects of treatment were observed up to 6 months, 12
      weeks, and 9 months, respectively. RESULTS: In all cases, patency of the stenosed
      areas was achieved with minimal bleeding and at least some degree of
      normalization of the glottic and subglottic mucosa. Airway patency and laryngeal
      functions were restored without complications. CONCLUSIONS: The use of spray
      cryotherapy alone or in conjunction with balloon dilation is a promising and
      effective therapeutic approach to treating glottic and subglottic narrowing.

PMID- 20058315
TI  - Ambulatory sinus and nasal surgery in the United States: demographics and
      perioperative outcomes.
AB  - OBJECTIVES/HYPOTHESIS: Determine the prevalence of ambulatory sinonasal surgical
      procedures and perioperative outcomes in the United States. METHODS: The National
      Survey of Ambulatory Surgery 2006 release was examined, extracting all cases of
      nasal or sinus surgery. Sinonasal surgical procedures were grouped according to
      septoplasty and/or turbinate surgery, sinus surgery, facial plastic surgery, and
      other procedures. Overall and group population-based sinonasal procedure
      prevalences were estimated from the sample. Frequency of general anesthesia,
      discharge status, and unexpected emergency room visit estimates were obtained.
      Perioperative complication rates for cardiac arrest, malignant hyperthermia,
      postoperative emesis, and blood transfusion were determined as well. RESULTS:
      Overall, an estimated 600,000 patients underwent ambulatory sinonasal procedures
      in 2006 with a mean age of 40.4 years and 53.7% male predominance. On a per
      patient basis, there were 260,000 septoplasties, 257,000 sinus cases, 134,000
      plastics cases, and 103,000 other cases. Facial plastics procedures were less
      likely to use general anesthesia (72.8%) than the overall cohort (90.7%, P <
      .001). The vast majority of patients were discharged to home with an unexpected
      admission rate of 2.65%. Among the sample, there were no cases of cardiac arrest,
      malignant hyperthermia, or blood transfusion. The postprocedure emesis rate was
      1.3%, not significantly different among procedure groups (P = .692). Only 0.1% of
      patients visited the emergency room postprocedure. CONCLUSIONS: Approximately
      600,000 ambulatory sinonasal cases are performed each year in the United States.
      Complication rates and unexpected postprocedure mission rates are quite low
      indicating the safety and effectiveness of the ambulatory setting for sinonasal
      surgery.

PMID- 20058316
TI  - Factors associated with developing cholesteatoma: a study of 45,980 children with
      middle ear disease.
AB  - OBJECTIVES/HYPOTHESIS: To identify factors associated with the rate of developing
      cholesteatoma following ventilation tube insertion (VTI). STUDY DESIGN: A
      population-based retrospective cohort study. METHODS: Administrative health data
      from all private and public hospitals in Western Australia for children who had
      at least one VTI from 1980 to 2004 was used to identify subsequent hospital
      admissions for cholesteatoma. Main outcome measures were time to cholesteatoma
      (survival) outcomes, including hazard ratios, log-rank tests, and Kaplan-Meier
      failure functions. RESULTS: There were 45,980 children who underwent at least one
      VTI from 1980 to 2004 with 460 subsequently developing cholesteatoma. The
      cumulative percentage of children who developed cholesteatoma within 15 years
      after one VTI procedure was 0.9% (95% confidence interval [CI], 0.8-1.0), after
      two VTIs 2.1% (95% CI, 1.6-2.3), after three VTIs 3.8% (95% CI, 2.9-4.8), and
      after four or more VTIs 5.2% (95% CI, 4.0-6.7). The rate of developing
      cholesteatoma increased 10% (95% CI, 6-14) for each additional year in age before
      first VTI. For children who underwent two or more VTIs, the rate of cholesteatoma
      increased 21% (95% CI, 12-32) with each additional year between VTIs. Adenoid
      removal was associated with a 27% (95% CI, 11-40) reduction in the rate of
      developing cholesteatoma. CONCLUSIONS: Children with persistent or refractory
      middle ear disease who required multiple VTIs were at increased risk of
      cholesteatoma. First ventilation tubes inserted at an early age, subsequent
      ventilation tubes inserted without delay, and adenoid removal were associated
      with a reduced rate of cholesteatoma development.

PMID- 20058317
TI  - Laryngeal mucous membrane pemphigoid: a systematic review and pooled-data
      analysis.
AB  - OBJECTIVES/HYPOTHESIS: To perform a systematic pooled-data analysis of literature
      data involving laryngeal mucous membrane pemphigoid (MMP). STUDY DESIGN: A
      systematic review and pooled-data analysis. METHODS: We conducted a systematic
      literature search of MEDLINE, EMBASE, Cochrane Central Register of Clinical
      Trials, Cochrane Database of Systematic Reviews, clinicaltrials.gov, and the
      National Guideline Clearinghouse databases without language restriction for
      studies including combinations of relevant terms. All authors independently
      screened the abstracts of the search results, identified articles eligible for
      review, and critically appraised the full-text studies. Pooled-data analyses and
      Kaplan-Meier survival analyses were conducted using SPSS version 16.0 software
      (SPSS Inc., Chicago, IL). RESULTS: Of the 2,524 citations reviewed, the included
      articles consisted of 63 case reports and 10 case series reporting on 141
      patients with laryngeal MMP. No clinical trials or comparative trials were found.
      The overall calculated prevalence of laryngeal MMP was 12.2% (95% confidence
      interval [CI], 11.5-12.9%) of cases of MMP or one in 10 million persons in the
      general population. Mean age at laryngeal MMP onset was 59.7 years (95% CI, 57.9
      61.1 years), and the supraglottis was the most commonly affected site (84.8%, 95%
      CI, 82.5-87.2%). Distribution among genders was equivalent (P = .655). The
      presence of antiepiligrin autoantibodies was associated with increased laryngeal
      involvement (Odds ratio 7.9, 95% CI, 3.9-16.0). The overall 5-year relative
      survival rate was 92.4% (standard error, 8.4) with a follow-up range of 1 to 221
      months. Standard medical therapy alone occasionally improved the condition;
      however, relapses were frequent, and 10.5% eventually required tracheostomy.
      Laryngeal surgical interventions seemed to be effective in severe cases.
      CONCLUSIONS: Laryngeal MMP is a rare condition that can be life threatening
      without proper treatment and frequent follow-up.

PMID- 20058318
TI  - Transplantation of bone marrow-derived neurospheres into guinea pig cochlea.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the potential of neurally induced bone
      marrow stromal cells (BMSCs) as transplants for replacement of spiral ganglion
      neurons. METHODS: BMSCs were harvested from the femurs and tibias of adult guinea
      pigs. BMSCs were cultured with neural induction media and formed spheres. The
      capacity of BMSC-derived spheres for neural differentiation was examined by
      immunocytochemistry in vitro. BMSC-derived spheres were injected into the
      modiolus of the intact cochleae or those locally damaged by ouabain, followed by
      histological and functional analyses. RESULTS: In vitro analysis revealed a high
      capacity of BMSC-derived spheres for neural differentiation. After
      transplantation into the cochlear modiolus, the survival and neural
      differentiation of BMSC-derived spheres was observed in both the intact and
      damaged cochleae. In intact cochleae, transplants settled in various portions of
      the cochlea, including the cochlear modiolus, whereas in damaged cochleae,
      transplants were predominantly observed in the internal auditory meatus.
      Transplantation of BMSC-derived spheres resulted in no functional recovery of the
      cochlea or protection of host spiral ganglion neurons. CONCLUSIONS: The present
      findings indicate that BMSC-derived spheres can be a source for replacement of
      spiral ganglion neurons, although further manipulations are required for
      functional recovery.

PMID- 20058319
TI  - A nonrandomized comparison of potassium titanyl phosphate and CO2 laser fiber
      stapedotomy for primary otosclerosis with the otology-neurotology database.
AB  - OBJECTIVES/HYPOTHESIS: To compare short-term hearing results in patients
      undergoing laser stapedotomy for primary otosclerosis using either the flexible
      potassium titanyl phosphate (KTP) or CO(2) laser fiber. STUDY DESIGN: Prospective
      nonrandomized clinical study at a tertiary referral center. METHODS: Two hundred
      fourteen patients undergoing 214 stapedotomies for otosclerotic stapes fixation
      were enrolled in this study from January 2008 to January 2010. Comparative
      analyses were made between a group of 107 patients who underwent stapedotomy with
      the flexible KTP laser fiber and 107 patients who underwent stapedotomy with the
      flexible CO(2) laser fiber. Preoperative and postoperative audiometric evaluation
      at 3 months using conventional audiometry, namely, air-bone gap (ABG), bone
      conduction thresholds, and air-conduction thresholds, were assessed. RESULTS: In
      the KTP laser group the postoperative ABG was 4.3 dB compared to 3 dB in the
      CO(2) group, which is a mean difference of 1.3 dB (95% confidence interval [CI], 
      0.3 to 2.8; P = .10). Of the patients from the KTP group, 92% had a postoperative
      ABG of 10 dB or less, as compared to 97% in the CO(2) group (mean difference 5%;
      95% CI, -10 to 1; P = .14). The postoperative ABG at 4 kHz was 4.9 dB in the KTP
      and 2.2 dB in the CO(2) group, which is a mean difference of 2.7 dB (95% CI, 0.6
      4.7, P = .01). No sensorineural hearing loss was reported. CONCLUSIONS: The use
      of the CO(2) laser fiber appears to be associated with slightly better hearing
      results than the KTP laser fiber, especially when assessed at the 4 kHz
      frequency.

PMID- 20058320
TI  - Septoplasty retards midfacial growth in a rabbit model.
AB  - OBJECTIVES/HYPOTHESIS: Septoplasty in the prepubertal age group is a
      controversial operation because of concerns regarding retardation of subsequent
      midfacial growth. This study uses a validated rabbit snout model to determine if
      septoplasty results in midfacial growth retardation, and if the retardation can
      be averted by replacing resected cartilage with a porous polyethylene implant.
      STUDY DESIGN: Prospective controlled animal study. METHODS: Sixteen 9-week-old
      New Zealand white rabbits were divided into four groups: two control and two
      experimental. The experimental groups both underwent conservative
      submucoperichondrial surgical excision of a portion of their septum, leaving a
      generous dorsal and caudal septal strut for nasal support similar to what would
      be done clinically in humans. One of the experimental groups had replacement of
      the resected area by a rigid porous polyethylene graft, and in the other
      experimental group the resected area was left empty. Cephalometric measurements
      were performed on radiographs taken at the time of implantation, and at sacrifice
      when the rabbits were mature at 24 weeks of age. RESULTS: There were significant
      disturbances in snout growth between experimental and control groups, and no
      significant differences between the two experimental groups or between the two
      control groups. CONCLUSIONS: These data demonstrate midfacial growth retardation
      after conservative septoplasty in young rabbits, and that this retardation could
      not be averted by replacing the resected cartilage with a porous polyethylene
      graft. These data are in agreement with human studies.

PMID- 20058321
TI  - Modulatory effects of 5Hz rTMS over the primary somatosensory cortex in focal
      dystonia--an fMRI-TMS study.
AB  - Dystonia is associated with impaired somatosensory ability. The
      electrophysiological method of repetitive transcranial magnetic stimulation
      (rTMS) can be used for noninvasive stimulation of the human cortex and can alter
      cortical excitability and associated behavior. Among others, rTMS can
      alter/improve somatosensory discrimation abilities, as shown in healthy controls.
      We applied 5Hz-rTMS over the left primary somatosensory cortex (S1) in 5 patients
      with right-sided writer's dystonia and 5 controls. We studied rTMS effects on
      tactile discrimination accuracy and concomitant rTMS-induced changes in
      hemodynamic activity measured by functional magnetic resonance imaging (fMRI).
      Before rTMS, patients performed worse on the discrimination task than controls
      even though fMRI showed greater task-related activation bilaterally in the basal
      ganglia (BG). In controls, rTMS led to improved discrimination; fMRI revealed
      this was associated with increased activity of the stimulated S1, bilateral
      premotor cortex and BG. In dystonia patients, rTMS had no effect on
      discrimination; fMRI showed similar cortical effects to controls except for no
      effects in BG. Improved discrimination after rTMS in controls is linked to
      enhanced activation of S1 and BG. Failure of rTMS to increase BG activation in
      dystonia may be associated with the lack of effect on sensory discrimination in
      this group and may reflect impaired processing in BG-S1 connections.
      Alternatively, the increased BG activation seen in the baseline state without
      rTMS may reflect a compensatory strategy that saturates a BG contribution to this
      task.

PMID- 20058322
TI  - Scaffold-free tissue-engineered cartilage implants for laryngotracheal
      reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: Donor site morbidity, including pneumothorax, can be a
      considerable problem when harvesting cartilage grafts for laryngotracheal
      reconstruction (LTR). Tissue engineered cartilage may offer a solution to this
      problem. This study investigated the feasibility of using autologous chondrocytes
      to tissue-engineer scaffold-free cartilage grafts for LTR in rabbits to avoid
      degradation that often arises from an inflammatory reaction to scaffold carrier
      matrix. STUDY DESIGN: Animal study. METHODS: Auricular cartilage was harvested
      from seven New Zealand white rabbits, the chondrocytes expanded and loaded onto a
      custom-made bioreactor for 7 to 8 weeks to fabricate autologous scaffold-free
      cartilage sheets. The sheets were cut to size and used for LTR, and the rabbits
      were sacrificed 4, 8, and 12 weeks after the LTR and prepared for histology.
      RESULTS: None of the seven rabbits showed signs of respiratory distress. A
      smooth, noninflammatory scar was visible intraluminally; the remainder of the
      tracheal lumen was unremarkable. Histologically, the grafts showed no signs of
      degradation or inflammatory reaction, were covered with mucosal epithelium, but
      did show signs of mechanical failure at the implantation site. CONCLUSIONS: These
      results show that autologous chondrocytes can be used to fabricate an implantable
      sheet of cartilage that retains a cartilage phenotype, becomes integrated, and
      does not produce a significant inflammatory reaction. These findings suggest that
      with the design of stronger implants, these implants can be successfully used as
      a graft for LTR.

PMID- 20058323
TI  - Connexin36 is required for gap junctional coupling of most ganglion cell subtypes
      in the mouse retina.
AB  - Converging evidence indicates that electrical synaptic transmission via gap
      junctions plays a crucial role in signal processing in the retina. In particular,
      amacrine and ganglion cells express numerous gap junctions, resulting in
      extensive electrical networks in the proximal retina. Both connexin36 (Cx36) and
      connexin45 (Cx45) subunits are widely distributed in the inner plexiform layer
      (IPL) and therefore are likely contribute to gap junctions formed by a number of
      ganglion cell subtypes. In the present study, we used the gap junction-permeant
      tracer Neurobiotin to compare the coupling pattern of different ganglion cell
      subtypes in wild-type (WT) and Cx36 knockout (KO) mouse retinas. We found that
      homologous ganglion-to-ganglion cell coupling was lost for two subtypes after
      deletion of Cx36, whereas two other ganglion cell subtypes retained homologous
      coupling in the KO mouse. In contrast, deletion of Cx36 resulted in a partial or
      complete loss of ganglion-to-amacrine cell heterologous coupling in 9 of 10
      ganglion cell populations studied. Overall, our results indicate that Cx36 is the
      predominant subunit of gap junctions in the proximal mouse retina, expressed by
      most ganglion cell subtypes, and thereby likely plays a major role in the
      concerted activity generated by electrical synapses.

PMID- 20058324
TI  - Hind-limb paraparesis in a rat model for neurolathyrism associated with apoptosis
      and an impaired vascular endothelial growth factor system in the spinal cord.
AB  - Neurolathyrism is a motor neuron disease characterized by lower limb paraparesis.
      It is associated with ingestion of a plant excitotoxin, beta-N-oxalyl-L-alphabeta
      diaminopropionic acid (L-beta-ODAP), an agonist of alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA)/kainate-type glutamatergic receptors.
      Previously, a limited model of neurolathyrism was reported for the rat. To
      improve upon the model, we stressed rat pups by separation from their mothers,
      followed by the subcutaneous L-beta-ODAP treatment, resulting in a 4.6-fold
      higher incidence (14.0-15.6%) of the paraparesis compared with the prior study.
      The number and size of motor neurons in these rats were decreased only in the
      lumbar and sacral cord segments, at approximately 13-36 weeks after treatment.
      Only lumbar and sacral spinal cord tissue revealed pathological insults typical
      of physical and ischemic spinal cord injury in the surviving motor neurons. In
      addition, extensive but transient hemorrhage occurred in the ventral spinal cord
      parenchyma of the rat, and numerous TdT-mediated dUTP-biotin nick end-labeling
      (TUNEL)-positive cells were also observed. In parallel, vascular endothelial
      growth factor receptor (VEGFR)-2 (Flk-1) levels were significantly lowered in the
      lumbosacral spinal cord of the paraparetic rats compared with their controls,
      suggesting a failure of the VEGF system to protect neurons against L-beta-ODAP
      toxicity. We propose, based on these data, a novel pathological process of motor
      neuron death induced by peripheral L-beta-ODAP. For the first time, we present a
      model of the early molecular events that occur during chemically induced spinal
      cord injury, which can potentially be applied to other neurodegenerative
      disorders.

PMID- 20058325
TI  - Structural and functional characterization of a promiscuous feruloyl esterase
      (Est1E) from the rumen bacterium Butyrivibrio proteoclasticus.
AB  - The release of polysaccharide from the plant cell wall is a key process to
      release the stored energy from plant biomass. Within the ruminant digestive
      system, a host of commensal microorganisms speed the breakdown of plant cell
      matter releasing fermentable sugars. The presence of phenolic compounds, most
      notably ferulic acid (FA), esterified within the cell wall is thought to pose a
      significant impediment to the degradation of the plant cell wall. The structure
      of a FA esterase from the ruminant bacterium Butyrivibrio proteoclasticus has
      been determined in two different space groups, in both the apo-form, and the
      ligand bound form with FA located in the active site. The structure reveals a new
      lid domain that has no structural homologues in the PDB. The flexibility of the
      lid domain is evident by the presence of three different conformations adopted by
      different molecules in the crystals. In the FA-bound structures, these
      conformations show sequential binding and closing of the lid domain over the
      substrate. Enzymatic activity assays demonstrate a broad activity against plant
      derived hemicellulose, releasing at least four aromatic compounds including FA,
      coumaric acid, coumarin-3-carboxylic acid, and cinnamic acid. The rumen is a
      complex ecosystem that efficiently degrades plant biomass and the genome of B.
      proteoclasticus contains greater than 130 enzymes, which are potentially involved
      in this process of which Est1E is the first to be well characterized.

PMID- 20058326
TI  - Solution structure of the C-terminal X domain of the measles virus phosphoprotein
      and interaction with the intrinsically disordered C-terminal domain of the
      nucleoprotein.
AB  - In this report, the solution structure of the nucleocapsid-binding domain of the
      measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description
      of the interaction between XD and the disordered C-terminal domain of the
      nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all
      alpha protein consisting of a three-helix bundle with an up-down-up arrangement
      of the helices. The solution structure of XD is very similar to the crystal
      structures of both the free and bound form of XD. One exception is the presence
      of a highly dynamic loop encompassing XD residues 489-491, which is involved in
      the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary
      chemical shift values for full-length N(TAIL) were used to define the precise
      boundaries of a transient helical segment that coincides with the XD-binding
      domain, thus shedding light on the pre-recognition state of N(TAIL). Titration
      experiments with unlabeled XD showed that the transient alpha-helical
      conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR
      resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange
      with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL)
      resonance behavior in the titration experiments is consistent with a complex
      binding model with more than two states.

PMID- 20058327
TI  - An improved LC-MS/MS method for simultaneous determination of 1,5
      dicaffeoylquinic acid and its active metabolites in human plasma and its
      application to a pharmacokinetic study in patients.
AB  - In this study, a sensitive, selective and reproducible liquid chromatography
      tandem mass spectrometry method for the simultaneous determination of 1,5
      dicaffeoylquinic acid (1,5-DCQA) and its active metabolites, 1-caffeoyl-5
      feruoylquinic acid and 1,5-O-diferuoylquinic acid, in human plasma, using
      puerarin as internal standard, was developed and validated. Analytes were
      extracted from plasma samples by liquid-liquid extraction with ethyl acetate,
      separated on a C(18) reversed-phase column with water containing 5 mM ammonium
      acetate and acetonitrile as the mobile phase and detected by electrospray
      ionization mass spectrometry in negative selected reaction monitoring mode. The
      accuracy and precision of the method were acceptable and linearity was good over
      the range 1-200 ng/mL for each analyte. In addition, the selectivity, extraction
      recovery and matrix effect were satisfactory too. The validated LC-MS/MS method
      was successfully applied to phase II clinical pharmacokinetic study of 1,5-DCQA
      in patients.

PMID- 20058328
TI  - Simultaneous determination of lamivudine, stavudine and nevirapine in human
      plasma by LC-MS/MS and its application to pharmacokinetic study in clinic.
AB  - A new high-throughput LC-MS/MS method for the simultaneous determination of
      lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) in human plasma is
      presented, with zidovudine as an internal standard. The analytes were extracted
      from plasma by protein precipitation and only 150 microL plasma was needed.
      Chromatographic separation was achieved on a Shiseido C(8) column (150 x 2.0 mm,
      5 microm) with a total run time of 6 min. A tandem mass spectrometric detection
      was conducted using multiple reaction monitoring under positive ionization mode
      with an electrospray ionization interface. The method was developed and validated
      over the concentration range of 25-5000 ng/mL for 3TC and NVP and 20-4000 ng/mL
      for d4T. The method was validated in terms of intra- and inter-day precision (<
      or = 8.6%), accuracy (within +/- 8.4%), linearity and specificity. The method has
      been successfully applied to the pharmacokinetic study of a combination treatment
      of 300 mg lamivudine, 30 mg stavudine and 200 mg nevirapine in 22 healthy male
      volunteers under fasting conditions.

PMID- 20058329
TI  - Deterministic one-to-one synthesis of germanium nanowires and individual gold
      nanoseed patterning for aligned nanowire arrays.

PMID- 20058330
TI  - Aspects of human disease. 38. Idiopathic thrombocytopenic purpura (ITP).

PMID- 20058331
TI  - New Joint Commission center to take on wrong-site surgery.

PMID- 20058332
TI  - Ribavirin treatment for Crimean-Congo hemorrhagic fever.

PMID- 20058333
TI  - [Radiologic manifestations of Legionnaire's disease].

PMID- 20058334
TI  - [Abstracts to the 102nd Annual Meeting of the Japanese and Korean Society of
      Animal Reproduction. September 9-12, 2009. Nara, Japan].

PMID- 20058335
TI  - Variation in hospital mortality associated with surgery.

PMID- 20058336
TI  - Renal failure in cirrhosis.

PMID- 20058337
TI  - Renal failure in cirrhosis.

PMID- 20058338
TI  - Parenteral nutrition in the critically ill patient.

PMID- 20058339
TI  - Parenteral nutrition in the critically ill patient.

PMID- 20058340
TI  - Parenteral nutrition in the critically ill patient.

PMID- 20058341
TI  - Parenteral nutrition in the critically ill patient.

PMID- 20058342
TI  - Screening for colorectal cancer.

PMID- 20058343
TI  - A diagnostic niche for MRCP.

PMID- 20058344
TI  - Alcohol.

PMID- 20058345
TI  - The Berger rhythm: potential changes from the occipital lobes in man.

PMID- 20058346
TI  - What's the game plan?
AB  - With all the players assembled, the Obama administration's public health team is
      set to take on some pressing threats amid a weakened economy and in the shadow of
      reform efforts. "I think that the previous administration did lay a good
      foundation, but what we saw over time was the foundation erode. There wasn't a
      consistent interest in supporting the preparedness work over time," says public
      health expert Robert Pestronk, left.

PMID- 20058347
TI  - Anticipation. House action galvanizes both sides of the aisle.

PMID- 20058348
TI  - Drug discount out. House measure could save $1 billion if put back in.

PMID- 20058349
TI  - As CIT reorganizes... borrowers await outcome of filing.

PMID- 20058350
TI  - McAllen chronicles continue. Universal's settlement brings more finger-pointing.

PMID- 20058351
TI  - Uncomped care costs up in '09. For-profits stave off major losses with cost
      control.

PMID- 20058352
TI  - Building blocks. Economy causes many projects to stagnate.

PMID- 20058353
TI  - Of problems and solutions. Issues with variable-rate bonds, medical errors led
      our recent coverage.

PMID- 20058354
TI  - Taking their cuts. Second annual Purchasing Power Survey shows one proven way for
      large employers to restrain healthcare spending--staff reductions.

PMID- 20058355
TI  - Healthcare purchasing power.

PMID- 20058357
TI  - Protect the employer-based system. Expand 'value-based purchasing' as part of
      structural healthcare reform.

PMID- 20058356
TI  - Make it health quality reform. Overemphasizing changes in health insurance market
      won't get the job done.

PMID- 20058359
TI  - It won't mean a thing... if Dems ain't got that swing vote in Senate.

PMID- 20058358
TI  - Stretching the limits. Hospitals watch as Supreme Court considers taking Michigan
      case that would expand their responsibilities under EMTALA.
AB  - A case now awaiting possible Supreme Court review threatens to upend what has
      long been established as the limits of hospitals' responsibilities under EMTALA
      to treat patients. The appeals court ruling raises many questions for hospitals.
      "When will a patient be considered stable under this?" says Amy Barkholz.

PMID- 20058360
TI  - Progressives not pleased. Stern, Dean decry watered-down Senate bill.

PMID- 20058361
TI  - Audits may hinge on upcoding. RAC expansion has hospitals wary of how much work
      it means for them.

PMID- 20058362
TI  - Search dearth. Experts say exec recruiting to stay slow into 2010.

PMID- 20058363
TI  - IPO seen as disappointment. But Team Health execs reap nearly $36 million.

PMID- 20058364
TI  - One down, one up. AMA loses $21.3 million; MGMA gains $1.8 million.

PMID- 20058365
TI  - Hoosiers unite. Indiana doc-owned hospitals form association.

PMID- 20058366
TI  - Sorting out the news. In a year filled with big stories, it's your turn to vote
      on what was biggest.

PMID- 20058367
TI  - Why this was a year to remember. Looking back on 2009.

PMID- 20058368
TI  - Providing an option? Some experts say provider-owned health plans could be model
      for reform.

PMID- 20058369
TI  - Re: Ethical practice under fire: deployed physicians in the global war on
      terrorism.

PMID- 20058370
TI  - Re: Cerebral air embolism following removal of central venous catheter.

PMID- 20058372
TI  - Holding steady. Recession brings no surge in uncompensated care.

PMID- 20058371
TI  - Here, there and everywhere. With the release of MedPAC report on differences in
      regional Medicare spending, some providers are concerned government might
      overreact.
AB  - A MedPAC report that details regional differences in Medicare service use has
      providers worried what solutions policymakers will come up with to deal with the
      disparities. The study "compels us to ask why the variation is occurring and what
      steps can be taken now to rein in the variation where it is unjustified," says
      Karl Ulrich, left, of the Marshfield (Wis.) Clinic.

PMID- 20058373
TI  - Scott & White proceeds. FTC mum on reported orders to try to sell facility.

PMID- 20058374
TI  - Breach law uncovers shortfalls. Experts say problems exist keeping data secure.

PMID- 20058375
TI  - Stryker's new tack. Equipment maker moves into device-reuse business.

PMID- 20058376
TI  - Mammogram debate. New guidelines disputed at RSNA.

PMID- 20058377
TI  - Give the gift of prevention. Sharing resources can be the key to successful
      intervention efforts.

PMID- 20058378
TI  - When ethics fail. Learning to spot the warnings of compliance failure.

PMID- 20058379
TI  - A long way to go. In the decade since the IOM's groundbreaking study on medical
      errors, there's progress to report, but many of the objectives remain elusive.

PMID- 20058380
TI  - Competition. Burnham's flawed regime will stifle commissioning ambitions.

PMID- 20058381
TI  - NHS recruitment feels the squeeze as half of organisations plan to axe jobs.

PMID- 20058382
TI  - Embrace new era of redesign to take NHS from good to great.

PMID- 20058383
TI  - Why Burnham is wrong to rip the competition rulebook.

PMID- 20058384
TI  - Decommissioning. Face the facts of changing needs.

PMID- 20058385
TI  - Stop smoking services. Keep quitters winning.

PMID- 20058386
TI  - Human resources. The momentum to drive change.

PMID- 20058388
TI  - Napping may not be such a no-no.  Research is showing that the daytime snooze may
      have benefits and not interfere with nighttime sleep.

PMID- 20058387
TI  - Legal. Money back guarantee.

PMID- 20058390
TI  - A sport for all seasons.  Swimming has myriad physical and psychological benefits
      at almost any stage or state of life.

PMID- 20058389
TI  - The male face of osteoporosis.  As men live longer, they're having to cope with a
      condition that used to be thought of as a women's disease.

PMID- 20058391
TI  - Side effects: minor can add up to major. Many medications have relatively minor
      anticholinergic effects that may add up, causing mental decline and other
      impairments.

PMID- 20058392
TI  - By the way, doctor. I have been diagnosed with temporal arteritis and am being
      treated with a drug called prednisone, which the doctor says is a steroid. I know
      athletes use steroids to bulk up, and I can't see how that would have anything to
      do with temporal arteritis. Can you explain?

PMID- 20058393
TI  - How to investigate religious experiences in psychiatry.

PMID- 20058394
TI  - The evolution of U.S. temperance movements since repeal: a comparison of two
      campaigns to control alcoholic beverage marketing, 1950s and 1980s.
AB  - This paper compares the politics of a failed religious movement to ban alcohol
      advertising in the 1950s with the politics of a more secular, and partially
      successful, movement to regulate alcohol marketing in the 1970s and 1980s.
      Although the contexts of the two marketing control movements were quite
      different, the continuities were equally striking. Both employed arguments about
      youth, social order, and the power of mass media.

PMID- 20058395
TI  - Opiate addiction and the entanglements of imperialism and patriarchy in
      Manchukuo, 1932-45.
AB  - In the Japanese colonial state of Manchukuo, opiate addiction was condemned by
      officials and critics alike. But the state-sponsored creation of a monopoly,
      opium laws, and rehabilitation programs failed to reduce rates of addiction.
      Further, official media condemnation of opiate addiction melded with local
      Chinese-language literature to stigmatise addiction, casing a negative light over
      the state's failure to realise its own anti-opiate agenda. Chinese writers were
      thus transfixed in a complex colonial environment in which they applauded
      measures to reduce harm to the local population while levelling critiques of
      Japanese colonial rule. This paper demonstrates how the Chinese-language
      literature of Manchukuo did not simply parrot official politics. It also
      delegitimised Japanese rule through opiate narratives that are gendered,
      consistently negative, and more critical of the state than might be expected in a
      colonial literature.

PMID- 20058396
TI  - Mr. ATOD's wild ride: what do alcohol, tobacco, and other drugs have in common?
AB  - All researchers agree that individuals can become intoxicated by and dependent on
      alcohol, tobacco, and other psychoactive drugs. But they have disagreed over
      whether, and to what extent, drug pathologies comprise a unitary medical problem.
      Most critically, does addiction have a biological common denominator? Consensus
      on this question has shifted back and forth. In the late nineteenth and early
      twentieth centuries, physicians often studied and treated various drug addictions
      together, working under the "inebriety" paradigm. By the mid-twentieth century
      the inebriety paradigm had collapsed. Tobacco and alcohol had split off, both in
      the medical research community and in western popular culture. This article
      argues that neuroscientific, genetic, epidemiological, and historical evidence
      helped to reunify the addiction field in the late twentieth century. A new
      unifying paradigm emerged, variously called chemical dependency, substance abuse,
      or simply ATOD -- alcohol, tobacco, and other drugs.

PMID- 20058397
TI  - Antithyroid drugs used in the treatment of hyperthyroidism  during breast
      feeding. An update and new perspectives.

PMID- 20058398
TI  - Psychiatric conditions in sports: diagnosis, treatment, and quality of life.
AB  - The social stigma surrounding psychiatric illness may prevent athletes from
      seeking counseling, psychotherapy, medication, or other treatment when needed.
      Few controlled studies on athletes exist to guide the team physician, clinician,
      or psychiatrist who must deal with diagnostic issues. Management involves setting
      realistic goals, educating as well as inducing the patient into treatment,
      soliciting support from family or significant others, and delivering appropriate
      treatment (the most difficult task). The objective is to improve performance and
      quality of life. Confidentiality issues are paramount during diagnosis and
      treatment. Physicians who understand sports and team dynamics may have more
      success in helping patients follow through with treatment.

PMID- 20058399
TI  - "Such a smoking nation as this I never saw...": smoking, nationalism, and
      manliness in nineteenth-century Hungary.
AB  - Tobacco smoking became an important marker of Hungarian national identity during
      the nineteenth century. this national symbol ultimately had an economic origin:
      Hungarian tobacco producers resisted the tobacco monopoly of the Habsburg central
      government, and led an ultimately successful consumer boycott of Austrian
      products. Tobacco nationalism, however, became a common theme in Hungarian
      popular culture in its own right, as tobacco use came to symbolize community and
      fraternity. The use of tobacco was also highly gendered; smoking as a metaphor
      for membership shows that the Hungarian nation was a gender-exclusive "national
      brotherhood."

PMID- 20058400
TI  - The Canadian cigar and tobacco journal in the forties: a remembrance.
AB  - This paper is a period snapshot of the life and times of Canadian smoking
      culture, filtered through "The Canadian Cigar and Tobacco Journal" (the
      industry's trade paper) from 1943-1949. "The Journal" provided a vivid portrait
      of neighbourhood tobacconists, travelling salesman, wholesalers and factory
      workers, homemakers and entrepreneurs. I discuss the role of Jews in the
      industry, as manufacturers and retailers. "The Journal" evokes the dangers of the
      retail trade, such as armed robberies, as well as the dangers of wartime. There
      is also the parallel danger of tobacco smoking, which, although not explicitly
      defined as risky behaviour by physicians, nonetheless is apparent to consumers.
      World War II is a dominant feature of "The Journal," and the celebration of
      wartime tobacco consumption is epitomized by Winston Churchill and other heroic
      smokers. Women's increased economic participation during the war years, and
      postwar demobilization, is reflected in "The Journal." Finally I discuss the
      growing targeting of children as potential consumers of tobacco.

PMID- 20058401
TI  - Creation of safety-net-based provider networks under the California Health Care
      Coverage Initiative: interim findings.

PMID- 20058403
TI  - Principles of surgical treatment of the cervical spine in rheumatoid arthritis.
AB  - About 20% of patients with rheumatoid arthritis complain about neck problems
      based on instability and deformity. As a consequence, pain, myelopathy, and
      severe neurological deficit may occur. Results reported in the literature were
      not encouraging as regards surgical decompression and stabilization. However, new
      surgical techniques allow a more aggressive strategy towards the complex problem
      of the instable cervical spine in rheumatoid arthritis. The most frequent
      instability of C1/2 can be stabilized by a posterior atlantoaxial screw fixation,
      a three-dimensional multidirectional construct with few complications. For the
      inclusion of the occiput into the fusion and the extension of the fusion down to
      the lower cervical spine, a titanium Y-plate is presented as a successful
      implant. While through a posterior approach, stability may be achieved,
      decompression is preferably done by anterior diskectomy or vertebrectomy.
      Encouraging results with a significant recovery of neurological deficits justify
      an early intervention in cases of instability of the cervical spine in rheumatoid
      arthritis.

PMID- 20058404
TI  - Paralysis of the arm after posterior decompression of the cervical spinal cord.
      I. Anatomical investigation of the mechanism of paralysis.
AB  - An anatomical study of the cervical spinal cord and root to investigate the
      mechanism of paralysis of the arm after posterior decompression was performed
      using 14 cadavers of Japanese adults. It revealed that in the intervertebral
      foramen, extradural portions of the anterior and posterior roots of the cervical
      spinal cord lay separately in caudal-rostral relation, and the anterior root
      passed through the narrowest portion of the foramen isolatedly, i.e. the superior
      notch of the superior articular process. After laminectomy, a posteromedial shift
      of the dura-root junction occurred in combination with the posterior enlargement
      of the dual tube, and it showed two effects on the roots, one a relaxing effect
      on rootlets and the other, a traction effect on the extradural portion of a root.
      Through these effects, the anterior and posterior rootlets did not lose their
      laxities even when there was maximal posterior shift of the spinal cord in the
      maximally enlarged dural tube, and conversely, extradural portions of both roots
      were laid under traction by the posteriorly expanded dural tube. This traction
      force to the extradural portion of the roots disappeared with a longitudinal
      incision to the posterior aspect of the bulging dural membrane, suggesting that
      it was the posteriorly expanded dural membrane that exerted the traction force on
      the extradural components of the anterior and posterior roots. From these
      anatomical findings, mechanisms of paralysis were deduced as follows. The
      posteriorly expanded dural tube exerts traction force on the extradural portions
      of the anterior and posterior roots. With the impingement of the medial facet
      edge on the posterior root, a traction-compression injury of the posterior
      rootlets or extradural portion of the posterior root occurs. With anchoring of
      the anterior root inside the foramen, a traction injury of the anterior root
      develops. The predominance of paralysis at the middle cervical level could be
      explained by the higher degree of anterior protrusion of the superior articular
      process and the more frequent degenerative changes here than at other levels.
      These factors might inhibit the gliding abilities of the roots inside the
      foramina, with the formation of perineural fibrosis, predisposing the roots to
      damage by the traction force.

PMID- 20058405
TI  - Paralysis of the arm after posterior decompression of the cervical spinal cord.
      II. Analyses of clinical findings.
AB  - Paralysis of the arm with radicular distribution occurring after posterior
      decompression of the cervical spinal cord included C5, C6, C7 and C8 roots, in
      isolation or combined. The most frequent patterns of paralysis were C5 and C6
      root involvements of the motor-dominant type. The overall frequency of occurrence
      in our series was 11% (20 cases of postoperative paralysis in 188 surgical
      cases), but the frequency varied with the posterior decompression method. The
      higher frequency of postoperative paralysis was noted in the group in which the
      surgical procedures selected were considered as enabling the expanded dura to
      exert its traction power more easily on the extradural portion of the roots.
      Radiographical analyses showed that C5 roots which satisfied the following two
      conditions were more prone to sustain postoperative paralysis: first, location at
      the level of the highly expanded dural tube and, second, lying in the foramina
      with a higher degree of anterior protrusion of the superior process. In the
      majority of cases with C5 motor-dominant paralysis, the postoperative cord-root
      pouch distances of the C5 anterior roots were unchanged or even decreased
      compared with the preoperative ones, but the extradural portions of the C5 roots
      were elongated in all cases. These findings support the validity of mechanisms of
      postoperative paralysis which were deduced from the anatomical investigations.

PMID- 20058406
TI  - Tensile properties of the annulus fibrosus. I. The contribution of fibre-matrix
      interactions to tensile stiffness and strength.
AB  - We investigated the tensile properties of samples of human lumbar annulus
      fibrosus. Here we consider the effect of sample size, and hence collagen
      disruption, on the results obtained. Vertical slices, 5 mm thick and 30 mm wide,
      were cut from the lateral margins of the annulus and adjacent vertebral bodies.
      The bony ends of each slice were secured in a materials testing machine so that
      the annulus could be stretched vertically, as occurs during bending movements of
      the spine in life. Tensile stiffness was measured repeatedly after successive
      vertical cuts in the annulus had reduced the effective size of the sample.
      Stiffness (per unit cross-sectional area) decreased as the specimen size
      decreased. The mean length of collagen fibre bundles in the specimens was
      calculated from a geometrical model and shown to be proportional to the tensile
      stiffness. Extrapolation of the results suggested that the vertical stiffness and
      strength of 15-mm-wide specimens of annulus would be about 44% of their values in
      situ. We conclude that collagen fibres need not be continous to reinforce the
      annulus and that fibre-matrix interactions make a large contribution to the
      tensile stiffness and strength.

PMID- 20058407
TI  - Tensile properties of the annulus fibrosus II. Ultimate tensile strength and
      fatigue life.
AB  - Part I of this study showed that collagen fibres do need not need to be
      continuous to reinforce the annulus fibrosus, and that 15-mm-wide samples of
      annulus retain about 44% of their in situ stiffness and strength when stretched
      vertically. Part II investigated the ultimate tensile strength (UTS) and fatigue
      life of such samples. Vertical slices, 5 mm thick and 30 mm wide, were cut from
      the anterior and posterior margins of the annulus and adjacent vertebral bodies.
      Each slice was divided sagittally to obtain a matched pair of specimens. The bony
      ends of each specimen were secured in a materials testing machine so that the
      annulus could be stretched vertically, as occurs during bending movements of the
      spine in life. One of each pair of specimens was stretched to failure to obtain
      its UTS; the other was cyclically loaded at some fraction of the UTS until
      failure occurred. Tensile failure started with the hyaline cartilage end-plate
      being stripped off the underlying bone and ended with the most peripheral annular
      fibres pulling out of the matrix. The estimated in situ strength in the vertical
      direction was 3.9 MPa for the anterior annulus and 8.6 MPa for the posterior
      annulus. Fatigue failure could occur in less than 10000 cycles if the tensile
      force exceeded 45% of the UTS. The results explain why radial fissures often fail
      to penetrate the peripheral annulus. When compared with in vivo measurements of
      spinal loading, they suggest that repetitive forward bending movements could
      cause fatigue failure of the posterior annulus.

PMID- 20058408
TI  - Discomanometry in lumbar intervertebral discs: an experimental study.
AB  - A new discomanometry system was developed and evaluated for application in the
      lumbar spine. The diagnostic reliability of discography, manometry and
      discomanometry (a combination of both methods) was assessed in 20 lumbar cadaver
      spines (95 intervertebral discs) with regard to the diagnosis of non-contained
      intervertebral discs. The sensitivity was 92% for manometry and 78% for
      discography. This indicates that 22% of the non-contained discs could not be
      correctly identified with common discography. The specificity was 98% for
      manometry and 100% for discography, indicating that contained discs could be
      easily identified with both methods. A combination of manometry and discography
      provides a high sensitivity (98%) as well as high specificity (98%). It is
      concluded that discomanometry is a simple, cost-effective and reliable diagnostic
      procedure which can precede percutaneous nucleotomy without additional risks or
      relevant efforts. It allows the differentiation between contained and non
      contained intervertrebral discs with a high degree of diagnostic reliability in
      an experimental setting, which justifies its further application in patients.

PMID- 20058409
TI  - The profile of multiple- versus single-operated patients at the time of their
      first operation for lumbar disc herniation.
AB  - A retrospective study was carried out on a total of 491 patients (294 male, 197
      female) who underwent surgery between 1 January 1980 and 31 December 1986. They
      were treated by minimal intervention lumbar discectomy without the use of a
      microscope. The patient groups consisted of 241 patients who needed a second
      operation (MOP, multiple operations) and another 250 patients who needed only one
      surgical procedure (SOP, single operation) and the whole treatment period was
      between 1 January 1980 and 31 December 1990. The SOP patients served as control
      group. The MOP and SOP groups were compared in the search for clinical and/or
      morphological parameters which might distinguish the two groups at the time of
      first operation. RESULTS: In terms of history, age, sex distribution, pre
      operative treatment and severity of neurological symptoms there was no
      statistical difference between the two groups at the time of the first operation.
      Radiological examinations were more extensive but less conclusive in the MOP
      group. In the SOP patients, subligamentous and epidural disc fragments occurred
      in 67.2% of patients. In the MOP patients disc protrusions or small
      subligamentous extrusions were predominant (50.1%) at the time of the first
      operation. Osteochondritic changes occurred less frequently in the MOP (39.1% vs
      53.6%). There were significantly more two-level approaches in the MOP patients
      (31.5% vs 14.4%); also, the surgical technique in the MOP group was less
      invasive, often being 'explorative' in character. Post-operative morbidity was
      higher, improvement of neurological symptoms was slower and the overall result
      was worse in MOP patients after the first operation. Interpretation of
      radiological findings, disc morphology and surgical technique are usually
      considered factors influencing the outcome of disc surgery. At the second
      operation (MOP 2) there were epidural scars in 48.4% of patients and the
      incidence of disc fragments containing parts of the end-plate increased from
      10.1% to 61.9%. The prognosis was worse in patients with mild pre-operative disc
      degeneration.

PMID- 20058410
TI  - Lumbar spine mobility in Marfan syndrome. A clinical and radiological study.
AB  - Low back pain symptoms and lumbar spine mobility were assessed by questionnaires
      and by clinical and radiological measurements in 32 patients with Marfan
      syndrome. Frequently occurring low back pain was reported by 19% of the patients,
      but the disability was slight in all of them. Flexion and extension mobility of
      the lumbar spine (L1-S1) assessed from radiographs was 59.9 degrees and 13.2
      degrees, respectively. Mean lumbar angular mobility between flexion and extension
      radiographs was 7.4 degrees at L1-2, 13.2 degrees at L2-3, 16.0 degrees at L3-4,
      19.3 degrees at L4-5 and 18.3 degrees at L5-S1. No correlation was found between
      the manual assessment of lumbar segmental instability and radiological
      translatory motion, except at L2-3, where the correlation was negative (r = 
      0.41, P < 0.05). In conclusion, the prevalence of low back pain does not seem to
      differ substantially between Marfan syndrome patients and the normal population,
      and it seems that there is at most a slight hypermobility of the lumbar spine in
      Marfan syndrome. Several validity problems are encountered in the manual
      assessment of lumbar instability.

PMID- 20058411
TI  - Freeze-dried allograft versus autograft bone in scoliosis surgery. A
      retrospective comparative study.
AB  - Two groups of 36 patients who underwent posterior vertebral fusion for scoliosis
      were compared retrospectively; the postoperative follow-up was 2 years.
      Autogenous bone taken from the iliac crest was used in group A, whereas the
      patients in group B received freeze-dried allograft from our bone bank. There was
      no significant difference between the two groups in maintenance of the curve
      correction after the same delay, nor in incidence of complications. A reduction
      of blood loss or operating time, however, could not be demonstrated in our study.

PMID- 20058412
TI  - Anaplastic large cell Ki-1 lymphoma arising in bone.
AB  - Anaplastic large cell Ki-1 lymphoma is a very rare tumour that involves
      predominantly lymph nodes, the skin and the gastrointestinal tract. This report
      describes the diagnosis and treatment of a case of anaplastic large cell Ki-1
      lymphoma arising in two thoracic vertebrae in a 14-year-old boy.

PMID- 20058413
TI  - Richard A. KERN Award Lecture. Building for the future. Reframing the questions.

PMID- 20058414
TI  - William C. Porter Award Lecture. Trauma disorders and a psychology of external
      experience.
AB  - The primary observation in this lecture is that there is a marked lack of
      attention to the actual, external objective reality and inherent objective
      meanings of the experiences of traumatic stress, which is due first to non
      rational aversive responses in clinicians and researchers to traumatic events.
      Secondly, the inhibition is due to processes and structures inherent in
      behavioral sciences, including bias against memory, and preoccupation with the
      individual to the exclusion of the external environment. These factors produce
      confusion about etiology and pathogenesis in the vulnerable field of traumatic
      stress, undue burdening of the victim or survivor for accounting of events, and
      inadequate diagnosis and treatment. Certain exceptions are at hand, in the work
      of few researchers and in publications from centers for the treatment of torture
      victims. A psychology of external experience is needed, to more deeply explore
      the objective meanings of traumatic events and search for accurate recording of
      external events in memory, in correlation with the established areas of trauma
      research. This requires some partial paradigm shifts to better support traumatic
      stress studies.

PMID- 20058415
TI  - Edward Rhodes Stitt Award Lecture. Will a computer (with artificial vision)
      replace the surgical pathologist (or other health professionals)?
AB  - Many jobs require vision for most of the tasks performed and the discussion
      focuses on the nature of human visual perception. Arguments are given to support
      the claim that visual perception is a very complicated function of the brain. To
      attempt to answer whether or not artificial intelligence (AI) will ever be able
      to essentially do what the brain does, the history and current state of AI
      research is examined, with special attention to neural net research.

PMID- 20058416
TI  - 1993 Federal Nursing Service Award recipient. Use of air-filled pads to reduce
      risk of intraoperatively acquired pressure ulcers.
AB  - This descriptive study utilized a two-phased retrospective review of medical
      records to investigate the development of pressure ulcers during cardiothoracic
      or vascular surgery. Using descriptive and chi-square statistics, the charts of
      104 patients having surgery on standard table pads were compared with those of
      124 patients having similar surgical procedures while positioned on air pads.
      Eight (8%) of the patients who had surgery without an air pad developed pressure
      ulcers, while none (0%) of the patients who were positioned on air pads developed
      pressure ulcers. Six (75%) of the eight patients who developed pressure ulcers
      were diabetic.

PMID- 20058417
TI  - 1993 Mary J. Nielubowicz Award recipient. Myth versus reality: in search of the
      Total Force concept.
AB  - The term Total Force has been historically used to describe the relationship
      between reserve and active components of the armed services. As a result of the
      Desert Storm experience, concerns about the Total Force concept in practice were
      identified by both reserve and active medical personnel. Utilizing the results of
      recent studies and input from reserve Navy Nurse Corps officers serving on active
      duty in key positions, this essay provides a clear definition of the Total Force
      concept and provides a model for implementation throughout the Navy Medical
      Department.

PMID- 20058418
TI  - 1993 New York-Tidewater chapters history of Military Medicine Essay Award
      recipient. Harvey Cushing: contributions to military surgery.

PMID- 20058419
TI  - 1993 Sir Henry Wellcome Medal and Prize recipient. The rise and fall of
      mefloquine as an antimalarial drug in South East Asia.
AB  - Mefloquine is an antimalarial drug developed by the U.S. Army Antimalarial Drug
      Program in conjunction with the World Health Organization and Hoffmann-La Roche
      to address the problem of chloroquine-resistant falciparum malaria encountered
      during the Vietnam War. Despite the expenditure of millions of dollars over a 20
      year period, it is unlikely that mefloquine will ever be used for U.S. soldiers
      deployed to South East Asia. Although mefloquine met the specifications set by
      its developers, its usefulness is now limited by the rapid evolution of drug
      resistance following its release to the civilian population. Drug development for
      particular military needs was compromised by a rapid biological response from the
      parasite and commercial concerns. In an era of shrinking military budgets,
      military drug development programs will by necessity be more resource
      constrained, thus yielding fewer new drugs per decade. In the short-term,
      emphasis should be directed toward adapting available antimicrobial drugs for
      antimalarial purposes.

PMID- 20058420
TI  - The war on cancer: demonstrating the impact of aging upon cancer mortality.
AB  - Despite two decades of concerted federal government effort and the expenditure of
      billions of dollars, the war on cancer, as judged by mortality, is not going
      well. However, the mortality yardstick by which progress against cancer is often
      measured should be reassessed based upon current concepts of carcinogenesis. The
      multistage model of carcinogenesis, assumed to reflect inherent genetic
      instability and the accumulation of multiple genetic abnormalities, has gained
      general acceptance. Accordingly, cancer cells typically display multiple
      characteristic abnormalities in presumed oncogenes and tumor suppressor genes.
      Age-specific cancer mortality rates in the United States from 1962 to 1988 were
      analyzed using the Strehler-Mildvan modification of the Gompertz relationship
      between aging and mortality. This method of analysis suggests that aging of the
      population, which allows for the manifestation of inherent genetic instability,
      rather than increasing environmental carcinogens, accounts for the continued rise
      in cancer mortality.

PMID- 20058421
TI  - Drug-induced akathisia: subjective experience and objective findings.
AB  - Drug-induced akathisia, especially antidepressant-induced akathisia, is a concern
      for mental health professionals of all disciplines, especially since the
      introduction of the so-called third-generation antidepressants such as
      fluoxetine. Failure to identify and treat this disorder can result in
      extraordinary suffering for the patient, which can in turn lead to preoccupation
      with the idea of suicide, specifically by jumping. The goal of this paper is to
      provide clinicians with an understanding of the protean presentations of this
      disorder along with a discussion of the current theories of etiology and
      pathophysiology as well as a strategy for identification and treatment.

PMID- 20058422
TI  - Mycoplasma pneumoniae and Chlamydia pneumoniae strain TWAR infections in U.S.
      Marine Corps recruits.
AB  - Paired sera from 208 healthy Marine Corps recruits undergoing 11 weeks of basic
      training in San Diego during 1989 were studied by complement fixation and
      microimmunofluorescence techniques for antibody to Mycoplasma pneumoniae and
      Chlamydia pneumoniae strain TWAR infections. Upon entering training, 52.7% and
      64.4% of the recruits had evidence of prior infection with M. pneumoniae and C.
      pneumoniae, respectively. At the end of training, 5.9% of recruits had evidence
      of new infections with M. pneumoniae (4-fold antibody rise) and 3.8% had evidence
      for new infections with C. pneumoniae (4-fold antibody rise). Recruits with
      evidence of previous infection with C. pneumoniae had a lower relative odds of
      new infection during training with this agent (odds ratio = 0.07, 95% confidence
      interval 0.00-0.61). These data demonstrate that, like their counterparts in
      Scandinavia, U.S. military recruits also suffer from C. pneumoniae infections.
      Both M. pneumoniae and C. pneumoniae should be considered as potential causes of
      respiratory disease among U.S. military trainees.

PMID- 20058423
TI  - The use of Delphi to identify current and future role perceptions for certified
      registered nurse anesthetists.
AB  - The proposed objective of this study was to identify current and future role
      perceptions for certified registered nurse anesthetists (C.R.N.A.s). Five
      C.R.N.A.s and five anesthesiologists were selected to participate on a Delphi
      panel to identify these roles. A four-round Delphi exercise was carried out
      resulting in 26 current roles and 28 future roles being identified. The rounds
      did not suffer any mortality and moved toward consensus on all of the roles
      identified.

PMID- 20058424
TI  - Suicides among draftees: biphasic occurrence of suicide during military service.
AB  - We analyzed all suicides among draftees during the 10-year period 1981-1990. The
      distribution of 50 suicides followed a bimodal curve with the first peak
      occurring 20-60 days from the beginning of the military service and the second
      peak during the early specialization training. Suicides committed during the
      basic training period were characterized by the absence of preceding alcohol
      intoxication, which was significantly more often seen in the suicides committed
      later during service. Most of the cases had been in contact with the medical
      personnel a short time before suicide. We discuss preventive measures, such as
      health education directed to both draftees themselves and the medical personnel.

PMID- 20058425
TI  - The epidemiology of sharps injuries and splash exposures at a military medical
      center.
AB  - Health care workers (HCWs) are subject to sharps injuries and splash exposures on
      a daily basis, and are therefore at risk for infection with a number of
      bloodborne pathogens. We conducted a review of sharps injuries and splash
      exposures at our institution. Although nursing personnel most often sustained
      sharps injuries, many HCWs from different patient care occupations are involved,
      and underreporting obscures the magnitude of the problem. Sharps injuries are
      most commonly caused by hollow-bore needles, although many devices in the
      hospital environment are capable of causing injury. Most sharps injuries occur
      after the device is used, but before disposal. Reducing the number of sharps
      injuries will require a multifaceted approach including reducing the need for
      using sharps, better HCW instruction in preventing injuries, and improved
      instrument design.

PMID- 20058426
TI  - Initial experience with laparoscopic cholecystectomy at an Army community
      hospital.
AB  - Laparoscopic cholecystectomy is associated with significantly less postoperative
      discomfort, a shorter hospital stay, and earlier return to normal activity
      compared with standard cholecystectomy. From February 1992 to January 1993, an
      initial 67 laparoscopic cholecystectomies were attempted at Irwin Army Community
      Hospital; 64 were completed, for a conversion rate of 4.5%. Average operative
      time was 127.3 minutes, but improved over the course of the series.
      Cholangiography was selectively performed for unclear biliary anatomy or possible
      choledocholithiasis, and was completed in 9 of 11 patients. Two procedure-related
      complications (3.1%) occurred. No biliary injuries or trocar injuries to
      intraabdominal contents occurred, and mortality was zero. Laparoscopic
      cholecystectomy can be safely performed at community hospitals by properly
      trained surgeons. Definitive identification of biliary anatomy, along with
      selective cholangiography and the Hasson method of trocar placement, can minimize
      the morbid injuries that are more common with this technique than with
      traditional cholecystectomy.

PMID- 20058427
TI  - Compliance with consultations in a military psychiatry clinic.
AB  - The study was undertaken to determine the effect of increased information in the
      referral process on compliance in routine consultations to a military outpatient
      psychiatry clinic. To evaluate the potential beneficial effects of facilitating
      factors in a clinic with over 70% baseline compliance, the psychiatrist's name
      and information about the clinic was provided to one-half of all patients who
      presented with a routine consult during a 2-month period. There was no increase
      in compliance rates for patients who were given more than standard information.
      These results have impact on manpower and staffing issues for the military.

PMID- 20058428
TI  - The need to be more efficient: lessons learned from a department of nursing
      reorganization.
AB  - The Department of Nursing at General Leonard Wood Army Community Hospital, Fort
      Leonard Wood, Missouri, recently reorganized to improve efficiency. Evening,
      night, and weekend supervisors were eliminated and a new "crisis nurse" role was
      established. Excess inpatient resources were shifted to outpatient clinics. The
      process of planning and implementing the reorganization is described. Evaluation
      was accomplished by reviewing objective criteria as well as outcomes of crisis
      nurse and middle management seminars and a comprehensive staff survey. The
      reorganization did not appear to adversely affect quality of patient care, but
      lessons were learned regarding staff morale, departmental communication patterns,
      clarification of newly established roles, and participation of middle managers in
      planning and decision making.

PMID- 20058429
TI  - Health goals of U.S. Army soldiers: what they want.
AB  - This study examined the personal health goals and needs of 1,299 soldiers during
      their periodic health exam at Fort Belvoir, Virginia, from January 1 to December
      31, 1990. The two most important goals of this population were improving self
      esteem (50%) and family relationships (43%). In contrast, smoking cessation (17%)
      and avoiding problems with alcohol (4.3%) were listed 14th and 19th priority, and
      were desired by only 56% and 61%, respectively, of those who needed help in these
      areas. Differences between soldiers' health goals and health needs must be
      considered when designing successful health-promotion programs.

PMID- 20058430
TI  - Relation of military service variables to posttraumatic stress disorder in New
      Zealand Vietnam War veterans.
AB  - In a community sample of 573 New Zealand Vietnam War veterans, 20% were
      identified as posttraumatic stress disorder (PTSD) cases. The association between
      PTSD diagnoses and a range of military experience variables and current
      demographic variables was examined. Significant differences were reported between
      cases and non-cases in terms of combat exposure, combat duties, length of service
      in Vietnam, length of service after Vietnam, total military service, and rank.
      PTSD cases also differed significantly from non-cases in terms of their age,
      marital status, income, educational qualifications, and employment status. These
      results confirm findings from previous studies showing that military experience
      in Vietnam is significantly associated with current levels of PTSD. They also
      suggest that veterans with PTSD have poorer social adjustment as indexed by
      factors such as their current marital and employment status.

PMID- 20058431
TI  - Continuing education needs of non-specialty-trained Army general dentists.
AB  - In this survey, preferences for dental continuing education (C.E.) topics for non
      specialty-trained Army general dentists were explored across personal and
      practice characteristics and were compared with C.E. topics that their
      supervisors think they need. Among general dentists, preferences for dental C.E.
      topics were found to vary across level of training, assignment location,
      experience, and presence of specialists in clinic of assignment. C.E. preferences
      of general dentists were found to be more narrowly clinically focused than those
      that their supervisors think they need. All groups ranked Management of Medical
      Emergencies as the most needed dental C.E. topic. The current inventory of Army
      dental C.E. courses is meeting the needs expressed by survey respondents with the
      exception of human relations courses. Topics such as Motivating Co-Workers,
      Management of Job Stress, and Working with Difficult People, which received high
      ratings in this survey, should be incorporated into the Army dental C.E. system.

PMID- 20058432
TI  - Parasitic causes of pancreatic and biliary tract disease: a growing concern in a
      highly mobile population.
AB  - A leading cause of biliary tract disease and pancreatitis worldwide is parasitic
      disease. In the United States, increased global travel and the AIDS epidemic has
      led to a rise in the frequency of parasitic disease. Biliary disease and
      pancreatic disease secondary to parasitic infestation is relatively new in this
      country, with the first case being described in 1977. These diseases are no
      longer the exclusive realm of infectious disease specialists and require general
      practitioners and gastroenterologists to be well versed in the spectrum of
      parasitic pancreatic and biliary disease.

PMID- 20058433
TI  - Stress fractures of bone in conscripted infantry recruits: lack of correlation to
      pre-army physical fitness.
AB  - The occurrence of stress fractures (SF) in 1,118 Israeli conscripted infantry
      recruits and their relation to the pre-army physical fitness as estimated from
      the results of a competitive field run were studied prospectively. About 8.5% of
      recruits sustained scintigraphy-proven SF during their basic training. The pre
      army physical fitness of recruits who sustained SF was not significantly
      different from that of recruits who did not. Tibial SF accounted for 57% of the
      total, metatarsal for 22.4%, and femoral for 17.9%. Other anatomical locations
      were rare. Twenty-eight of 35 (80%) femoral SF were asymptomatic. There were no
      cases of displaced SF at any site. Only one recruit had to discontinue training
      because of SF. Our data suggest that diminished pre-army physical fitness does
      not predispose recruits to SF, and that most scintigraphy-defined SF in
      conscripted infantry recruits are benign.

PMID- 20058434
TI  - U.S. Army rehabilitation advisors in El Salvador.
AB  - U.S. Army rehabilitation personnel have served in El Salvador since 1983 as
      advisors with the U.S. Army Humanitarian Medical Mobile Training Team. During 6
      month periods, they assisted in upgrading the rehabilitative skills and
      capabilities of their Salvadoran counterparts while obtaining experience in
      combat injuries and enhancing their own medical readiness. This article, authored
      by three of the physical therapists who served in this role, chronicles the
      challenges and successes of serving as a rehabilitation advisor in an area of low
      intensity conflict and offers preparatory information and recommendations to
      other health care professionals interested in serving in similar nation-building
      roles.

PMID- 20058435
TI  - Recurrent hematuria in a patient with a history of anaphylactic reaction to
      radiographic contrast.
AB  - Hematuria is a relatively common problem, but its evaluation can be complicated.
      One must pay attention to the patient's symptoms and extrarenal manifestations of
      disease to identify the etiology efficiently. We present the case of a patient
      who narrated a fascinating past medical history and a dramatic presentation of
      hematuria that had been exhaustively evaluated at another hospital. During a
      prolonged and involved stay at our institution, the etiology of the hematuria
      remained enigmatic after extensive radiologic and invasive investigations that
      led to internally inconsistent findings, until an unusual diagnosis was
      entertained.

PMID- 20058436
TI  - The amytal interview in the treatment of conversion disorder: three case reports.
AB  - The records of three consecutive patients who had a diagnosis of conversion
      disorder and received an amytal interview were reviewed. All diagnoses were made
      according to DSM-III-R criteria by a staff psychiatrist. Amytal was administered
      according to a previously published protocol. All patients were contacted 1 year
      following their hospital discharge. All patients tolerated the amytal interview
      without complications. The conversion symptoms in all patients remitted within
      several days of the interview and had not recurred at 1 year follow-up. In
      properly selected patients, the use of the amytal interview may be a safe, rapid,
      and efficacious intervention that can facilitate the resolution of conversion
      symptoms in the military setting.

PMID- 20058437
TI  - Hypnosis with the surgical patient.
AB  - Since World War I, hypnosis has been used by U.S. military medical personnel to
      treat shell shock, battle fatigue, and traumatic neurosis. Most recently,
      hypnosis has also been effective in the treatment of Vietnam combat veterans with
      post-traumatic stress disorder. Additionally, over 30 years ago, the American
      Medical Association endorsed the use of hypnosis by physicians and the teaching
      of hypnosis in medical schools. However, even with this rich tradition, there
      remains an underutilization of hypnosis within medical and surgical settings. To
      encourage the use of hypnosis, this paper reviews current literature concerning
      the benefits of employing hypnosis and positive outcome suggestions with surgery
      patients in a military hospital. Case studies are also included that describe the
      applications of hypnosis as an adjunct to successful surgical procedures.
      Practitioners are encouraged to learn more about hypnosis so as to determine the
      efficacy of this therapeutic modality as an appropriate addition to their
      treatment armamentarium. A protocol for hypnotic induction and positive
      suggestions with surgery patients is also included.

PMID- 20058438
TI  - Pulmonary artery laceration by a pulmonary artery catheter: a case report and
      review of the literature.
AB  - A 74-year-old white man with unstable angina underwent an uneventful urgent four
      vessel coronary bypass operation at which time a Tenkhoff catheter was placed
      because of renal insufficiency. Two hours following arrival in the intensive care
      unit, the patient demonstrated hemodynamic instability, progressive acidosis, and
      a fall in his hematocrit from 35% to 18%. In retrospect, this instability was
      initiated by wedging of the pulmonary artery catheter. Hemorrhagic complications
      involving the use of flow-directed, balloon-tipped catheters are rare following
      cardiopulmonary bypass operations. The estimated incidence is reported at 1 to 2
      per 1,000, although many may go unreported. The mortality rate is in excess of
      50%. We report a case of a successfully repaired laceration of the pulmonary
      artery caused by a pulmonary artery catheter following cardiac surgery, and
      provide a review of the literature. As illustrated by this case and emphasized in
      the literature, salvage of patients who suffer this complication requires a high
      index of suspicion in order to rapidly recognize the injury and intervene with
      the appropriate therapy.

PMID- 20058439
TI  - Perforation of the heart by an inferior vena cava filter.
AB  - The use of vena caval filters to prevent pulmonary emboli has become routine.
      Although the complications have been well described, we present the first
      reported case of perforation of the heart and subsequent cardiac tamponade
      several months following placement of a Gintureo-Roehm "bird's nest" filter.

PMID- 20058440
TI  - Burkitt's lymphoma of the testis.
AB  - A young man evaluated for a testis tumor was found to have Burkitt's lymphoma.
      The presentation of Burkitt's lymphoma in the United States as a testis mass is
      unusual. The rapid proliferation and metastatic potential of the tumor mandates
      prompt evaluation and the early initiation of systemic chemotherapy.

PMID- 20058441
TI  - Three-dimensional biomechanical properties of the human cervical spine in vitro.
      I. Analysis of normal motion.
AB  - Our aim was to determine the biomechanical properties of the normal human
      cervical spine under physiological static loads. The three-dimensional
      displacements under three pure moments: flexion-extension, left-right lateral
      bending and left-right axial torsion--were measured in 56 intact functional
      spinal units (FSUs) taken from between C2 and C7 in 29 human cadavers. For each
      mode of loading, load-displacement curves were plotted. Then we calculated each
      neutral zone, range of motion, neutral zone ratio, ratio of coupled motion, limit
      moment and secant stiffness. The effects of intervertebral disc degeneration and
      the disc level were also taken into account by the analysis of variance. Our
      results adequately demonstrated both the non-linearity of load-displacement
      curves and the neutral zone of the cervical spine in three-dimensional space. At
      the same time, we found statistically that the stiffness in the three planes are
      significantly different, as are the stiffnesses in lateral bending of successive
      different FSUs. However, significant differences of stiffness in different states
      of disc degeneration were only found in right lateral bending. There were
      significant differences between levels in ratio of coupled motion under both
      lateral bending and axial torsion. The loading cycle conditions and the
      biomechanical responses of principal motion of C1-2 are also reported.

PMID- 20058442
TI  - Three-dimensional biomechanical properties of the human cervical spine in vitro.
      II. Analysis of instability after ligamentous injuries.
AB  - We wanted to determine the biomechanical properties of the human cervical spine
      with ligamentous injuries. The three-dimensional displacements under four pure
      moments--flexion, extension, left-right lateral bending and left-right axial
      torsion--were measured in 18 functional spinal units (FSUs) taken from 9 human
      cadaveric cervical spines. The experimentation was first performed with intact
      FSUs, then a series of ligamentous injuries were artificially created. The same
      measurements for the same FSUs were repeated after each step of ligamentous
      injury. For each mode of loading and each step of injury, three-dimensional load
      displacement curves were plotted. From these curves, we calculated the following
      parameters for the principal motion: the neutral zone, the range of motion and
      the flexibility coefficients. A statistical analysis of these parameters was
      performed between intact FSUs and different ligamentous injury situations. The
      analysis of ligamentous injuries shows the consequences of different ligamentous
      injuries and will help us to assess certain assumptions about clinical stability.

PMID- 20058443
TI  - Response of the end-plates to compression of the spine.
AB  - The instantaneous displacement and creep of the caudal end-plate were measured
      during compression of six segments of cadaveric lumbar spine. Each segment
      consisted of a disc attached to the two adjacent vertebrae. It was subjected to
      an applied load of 1.6 kN which was supposed to be within the normal
      physiological range. End-plate displacement was measured using a displacement
      transducer. When the load was applied there was an almost instantaneous
      displacement of the end-plate of 0.14 +/- 0.04 mm (mean +/- standard deviation).
      The creep displacement in the specimens which remained undamaged was very small
      (0.023 +/- 0.006 mm) and associated with a retardation time of 1.9 +/- 1.1 s,
      i.e. the endplate displacement in these specimens reached an equilibrium value
      within a few minutes. Appreciable endplate displacement (exceeding 4 mm) was
      associated with damage which included fracture of the trabecular bone. In the
      damaged specimen, the end-plate continued to displace under a constant load. This
      result suggests that sustained compression could aggravate mechanical damage to
      the vertebra and end-plate in vivo.

PMID- 20058444
TI  - Restrictive pattern of pulmonary functions in idiopathic and congenital scoliosis
      following spinal fusion.
AB  - This paper presents the results of pulmonary function analysis in 141 subjects.
      Thirty-five of these were patients with adolescent idiopathic scoliosis, 36 had
      congenital scoliosis, and the remaining 70 were age-, sex-, height-, weight- and
      arm-span-matched normal subjects used as controls for adolescent idiopathic
      scoliosis. The patients with adolescent idiopathic scoliosis had their pulmonary
      function evaluated pre- and post-operatively. At pre-operative evaluation the
      mean age was 13.7 years and the mean cobb angle 48 degrees; at post-operative
      evaluation the figures were 17.1 years and 36 degrees respectively. In the
      congenital scoliosis group the mean age was 14.5 years and the mean Cobb angle 42
      degrees, and pulmonary functions were evaluated at a minimum of 3 years after
      surgery. The results are as follows: Adolescent idiopathic scoliosis: (i) Marked
      disproportion was found in the pulmonary volumes following spinal surgery. After
      taking growth of the thoracic cage into account, the total lung capacity remained
      unchanged whilst the vital capacity was significantly reduced and there was a
      significant increase in residual volume. (ii) This disproportionate increase in
      residual volume was further confirmed by very highly significantly increased
      residual volume/vital capacity and residual volume/total lung capacity ratios at
      post-operative evaluation compared to pre-operative ratios (Mann-Whitney test, P
      = 0.001). (iii) The residual volume was 48% of vital capacity preoperatively
      compared to 35% in normal controls. The percentages increased to 70% post
      operatively, whilst it was unchanged in the matched controls. Congenital
      scoliosis: (i) The mean residual volume was markedly increased (154% of predicted
      value). (ii) Vital capacity was significantly reduced in surgically treated
      patients (68% of predicted values). (iii) This pattern of reduced vital capacity
      was more marked in those patients who had multiple thoracic anomalies and were
      treated surgically (46% of predicted value). However, those patients with
      multiple thoracic anomalies who did not require surgery did not show such
      reduction of vital capacity. Comparison between idiopathic and congenital
      scoliosis: (i) In unoperated patients, the percentages of predicted values of
      total lung capacity, vital capacity and residual volume were significantly
      greater in congenital scoliosis than in adolescent idiopathic scoliosis. (ii)
      Post-operatively there was no significant difference in the percentages of
      predicted values of total lung capacity, vital capacity and residual volume
      between patients with congenital scoliosis and those with adolescent idiopathic
      scoliosis, despite the difference in pathogenesis. These findings have relevance
      to scoliotic patients treated with spinal fusion with regard to their capability
      to perform strenuous physical activities.

PMID- 20058445
TI  - Adolescent idiopathic scoliosis: is rising growth rate the triggering factor in
      progression?
AB  - The school scoliosis screening programme at Our Lady's Hospital for Sick
      Children, Dublin, has provided material for an ongoing prospective natural
      history study of adolescent idiopathic scoliosis. An examination of the clinical
      course in 339 girls showed that observation of progression of at least 10
      degrees, which occurred in 46 girls (13.6%), depended on the timing of diagnosis
      and related primarily to the child's position on her growth rate curve and her
      pubertal status, and much less to skeletal maturity as interpreted by iliac crest
      ossification or bone age. This has implications for the understanding of results
      in conservative management, screening programmes and natural history.

PMID- 20058446
TI  - Segmental vertebral rotation in early scoliosis.
AB  - In order to investigate the development of the vertebral axial rotation in
      patients with early scoliosis, the vertebral rotation angle (VRA) was quantified
      on the basis of 132 anteroposterior radiographs obtained from patients with
      diagnosed or suspected scoliosis. The rotation was measured in the apical
      vertebra and in the two suprajacent and two subjacent vertebrae. The radiographic
      material was divided into a control reference group and three scoliotic groups
      with varying Cobb angle from 4 degrees up to 30 degrees. In the reference group a
      slight vertebral rotation was significantly more often seen to the right. In the
      scoliotic groups, the rotation was most pronounced in the apical segments. The
      mean VRA toward the convex side was significantly increased in the vertebrae just
      suprajacent to the apex in curves with a Cobb angle of 8 degrees-15 degrees and
      in the cranial four vertebrae in curves with a Cobb angle of 16 degrees-30
      degrees. Atypical vertebral rotation to the opposite side of the major curve was
      observed in 12.8% of the cases. There was a significant positive correlation
      between the VRA and the Cobb angle. These results show that a slight VRA to the
      right is a common feature in the normal spine, and that the VRA increases with
      progressive lateral deviation of the spine. It is concluded that the coronal
      plane deformity in early idiopathic scoliosis is accompanied and probably coupled
      to vertebral rotation in the horizontal plane.

PMID- 20058447
TI  - Traumatic lesions of the lower cervical spine in Poland.
AB  - From 1965 through 1990 the Spinal Department of the Metropolitan Rehabilitation
      Center in Konstancin provided treatment to 1330 patients with spinal injury in
      the C5-T1 area admitted to hospital in the early post-traumatic period. The most
      common causes of injury were falls from a horse cart, diving, and road accidents,
      in that order. This paper presents an analysis of the dependencies between the
      degree of spinal cord injury and the mechanism of spinal injury, as well as the
      results of conservative and surgical treatment. The most serious lesions of the
      spinal cord were those following spinal injuries of a crush character and
      dislocations by a flexion mechanism. The injuries with the best prognosis were
      typical compression fractures of the vertebrae. Significant neurologic
      improvement was obtained in over 50% of patients. Improvement was greatest and
      most frequent in patients who received surgical treatment.

PMID- 20058448
TI  - Cervical myelopathy in patients with congenital cervical block vertebrae.
AB  - Thirty-two patients with congenital cervical block vertebrae are reviewed. Twenty
      nine patients had single level fusion, one had two-level fusion, and the
      remaining two had multilevel fusion. Eighteen patients had cervical myelopathy;
      five of these had related trauma and 13 had no history of trauma. The five
      patients who had cervical myelopathy following trauma underwent magnetic
      resonance imaging (MRI); three of them had abnormalities in the spinal cord at
      the segment adjacent to fusion. In all five patients the symptoms and signs were
      attributed to the segment adjacent to fusion. Myelography, computed tomographic
      myelography and MRI were performed in 11 of the 13 patients with cervical
      myelopathy without trauma. In 9 of them maximum compression of the spinal cord
      was not seen at the segment adjacent to fusion. The major factor contributing to
      cervical myelopathy was associated spinal canal stenosis. Seven patients with
      cervical myelopathy without history of trauma were treated surgically, six of
      whom had spinal canal stenosis treated by enlargement of the spinal canal:
      subtotal corpectomy and arthrodesis was performed in three, and open-door
      expansive laminoplasty in three. Anterior interbody arthrodesis was performed in
      one patient without spinal canal stenosis. All recovered from the myelopathy
      postopera-tively. When a trauma occurs, it concentrates stress at the segment
      adjacent to fusion, resulting in possible spinal cord injury. On the other hand,
      when there is no trauma, spinal canal stenosis is the principal factor
      contributing to cervical myelopathy.

PMID- 20058449
TI  - A rare anomaly of the tip of the odontoid process: case report and hypothesis as
      to aetiology.
AB  - A rare anomaly of the tip of the odontoid process is described. Possible
      congenital and traumatic origins of the anomaly are discussed.

PMID- 20058450
TI  - Scoliosis by acquired rib fusion after thoracotomy in infancy.
AB  - This is a report of a 6-year-old boy who was operated upon twice for congenital
      esophageal atresia immediately after birth, via a right posteriolateral
      thoracotomy without rib excision, and at the age of 5 years developed a high left
      convex thoracic scoliosis with Cobb angle of 15 degrees due to an unilateral
      acquired fusion between the dorsal ends of the fourth, fifth, and sixth ribs. The
      scoliosis had progressed by 5 degrees 1 year later. Although congenital scoliosis
      associated with rib fusion is a well known entity, to the authors' knowledge this
      is the first report of an acquired rib fusion producing progressive scoliosis.

PMID- 20058451
TI  - Synovial cyst of a lumbar facet joint: a rare cause of back pain and sciatica.
      Report of two cases.
AB  - Intraspinal synovial cysts, sometimes referred to as ganglion cysts, are uncommon
      lesions which may present as acute or chronic low back pain, with or without
      radicular symptoms. We present two patients who presented with back pain and
      radicular symptoms attributable to the unusual pathology of an intraspinal
      synovial cyst.

PMID- 20058452
TI  - Surgical management of the subaxial cervical spine (C3-T1) in rheumatoid
      arthritis.
AB  - In the process of skeletal changes in rheumatoid arthritis (RA) the lower
      cervical spine may characteristically be affected by subluxation,
      discoligamentous insufficiency and bone resorption. These may cause severe pain
      and important neurological deficit and necessitate surgical intervention. Out of
      a series of 122 RA patients who underwent surgery of the cervical spine, in 23
      the subaxial cervical spine was operated on. Pain was the leading symptom in all
      patients. In only six were there no pathological neurological findings, and all
      showed marked kyphotic deformity of the cervical spine. Fourteen patients were
      operated by a posterior approach, one by a ventral approach, and in eight
      patients the surgical procedure consisted of anterior decompression and dorsal
      stabilization. A mean of 21.3 months after surgery, clinical and radiological
      evaluation was performed. In two patients the sensomotor deficit improved, and
      out of 16 patients with cervical myelopathy, nine improved. No pseudoarthrosis
      was noted, and moderate loss of correction was seen in only three patients. In a
      subjective evaluation, 14 patients rated their result as good, six as fair and
      none as poor. In conclusion, following decompression, we noted good recovery from
      myelopathic symptoms. Sufficient stability in patients with RA is achieved by a
      combined anterior and posterior approach, the main goal of the anterior approach
      being decompression by vertebrectomy and that of the posterior approach
      stabilization by plate and screw fixation.

PMID- 20058453
TI  - Treatment problems in unilateral locked facet syndrome of the cervical spine.
AB  - In a retrospective study of 22 patients with unilateral locked facet syndrome of
      the cervical spine, diagnostic and treatment problems were analysed. Diagnosis
      was delayed in ten patients; in two-thirds of the patients minor or major
      therapeutic problems were encountered. The treatment protocol advised
      manipulative reduction and--before 1986--posterior fusion by bone blocks and
      interspinous wiring; after 1986 ventral intercorporeal fusion by plates was
      recommended. Closed reduction manoeuvres risk dislocation of intervertebral
      discs, overdistraction of the spinal cord or injury to the vertebral artery.
      Unreduced and unfused dislocations are likely to develop chronic instability.
      Dorsal wiring is an inadequate form of stabilization and ventral plates or dorsal
      hooks are preferred. To prevent treatment problems a treatment protocol is
      proposed according to which open reduction following anterior discectomy,
      operative decompression of endangered nerve roots and stable one-level fusion is
      done. In non-acute injuries neural structures are decompressed; posterior fusion
      is done without attempts at reduction.

PMID- 20058454
TI  - Attentional processing in common whiplash syndrome before and with immobilisation
      of the cervical spine.
AB  - The study focused on attentional processes in patients who had suffered common
      whiplash injury and who were investigated before and with immobilisation of the
      cervical spine. Patients demonstrated considerable subjective relief and marked
      improvement in complex attentional processing with the immobilisation. This
      improvement cannot be explained by the practice effect as shown by the results in
      a control group. The norepinephrine system is discussed as a possible
      neurophysiological basis for the observed effects.

PMID- 20058455
TI  - Anterior screw fixation for odontoid fracture: clinical results in 45 cases.
AB  - Clinical results of anterior screw fixation in 45 patients with odontoid
      fractures were reviewed retrospectively. The patients were 36 males and 9
      females, with fractures classified as 35 type II and 10 type III. There were 34
      fresh and 11 old fractures. Neurological complications were present in 16
      patients and 18 had associated injuries. All patients underwent single screw
      fixation. Postoperative immobilization, external support, and surgical trauma
      were minimal. In one patient a screw extruded from the dens and immediate
      posterior fusion was necessary. The overall rate of fracture union was 93% (41
      out of 44 fractures). Fracture resolution averaged 5.2 months. There were two
      delayed unions and three nonunions, the causes of which were preoperatively
      established nonunion, severe osteoporosis, and inaccurate screw placement. Out of
      11 old cases, 8 went on to union. Ninety-six percent of the patients recovered
      neurologically. The overall complication rate, including a misplaced screw, a
      retropharyngeal wall injury, and three nonunions, was 11%. Head rotation was
      preserved in 90% of the patients with fracture union according to clinical
      measurements. Anterior screw fixation is an excellent treatment for fresh type II
      and cephalad type III odontoid fractures, carrying a high union rate,
      preservation of the C1-2 motion segment, and minimal surgical trauma; it can be
      applied even to some old cases. Precise patient selection in regard to patient
      age, bone density, and time elapsed since injury as well as preoperative
      anatomical reduction and meticulous surgical technique with fine fluoroscopy are
      essential to avoid complications and nonunions.

PMID- 20058456
TI  - Anterior decompression and plate fixation in fracture dislocations of the lower
      cervical spine.
AB  - Surgical treatment of unstable traumatic injuries of the cervical spine can be
      carried out by a posterior or anterior approach, with different advantages and
      disadvantages. Twenty patients were treated with anterior decompression,
      interbody fusion with autogenous iliac bone graft, and osteosynthesis with a
      Louis anterior plate. The screws were inserted in the vertebral body without
      reaching the posterior vertebral wall. There were 18 male and 2 female patients,
      aged between 18 and 66 years (average 36 years). The osteoarticular lesion was in
      8 cases a tear-drop fracture and in 12 a fracture-dislocation. The mechanisms of
      injury were flexion-compression, flexion-rotation, hyperflexion, and
      hyperextension. A complete spinal cord lesion was present in 10 cases, central
      cord syndrome in 5, isolated radiculopathy in 3, and anterior cord syndrome in 1;
      one patient had normal neurological function. At long-term followup fusion of the
      graft was observed in all cases without evidence of spinal malalignment, breakage
      of the implant, or aseptic hardware loosening. Neurological deterioration was not
      observed in any case. In one case, complicated by late infection, healing was
      uneventful after plate removal, surgical debridement, and antibiotic therapy. A
      fistula of the hypopharynx due to perforation of the piriform recess appeared
      following repeated bronchoscopy 12 months after surgery. There were no signs of
      implant loosening and the lesion was surgically repaired. From a neurological
      point of view the 10 patients with complete cord lesion remained unchanged; those
      with incomplete cord lesions improved by 1 or 2 degrees on the Frankel scale;
      those with isolated radiculopathies recovered fully; and the neurologically
      intact patient remained unchanged. The present study and the data reported in the
      literature prove that anterior surgery with plate fixation in cervical spine
      injuries allows the achievement of complete neural decompression by direct visual
      examination. On the other hand, posterior surgery can result in incomplete
      decompression and associated neurological deterioration. Anterior plate
      instrumentation has proved itself mechanically adequate, even if it is less
      stable than posterior constructs. The advantages of anterior surgery compared to
      those of posterior surgery are such that several specific risks are acceptable.
      Posterior surgery is nevertheless indicated if the lesion cannot be reduced
      preoperatively under closed conditions.

PMID- 20058457
TI  - The R-zero line: a new kinematic concept of the lumbar spine.
AB  - A new kinematic concept is described that relates to the notion that the lumbar
      spine behaves as a complete structure. This concept is called the "R-zero line"
      and represents kinematically the neutral position of the lumbar spine between
      anteflexion and retroflexion. The clinical significance of this parameter is
      evaluated in normal individuals and in patients with a symptomatic herniated disc
      at L4-5, with a symptomatic herniated disc at L5-S1, and with
      spondylolysis/spondylolisthesis. The results of this study show that the R-zero
      line has a characteristic configuration in all four test groups.

PMID- 20058458
TI  - Measurement of blood flow to the vertebral bone and disc.
AB  - Measurements of blood flow were made in the endplate and disc of the vertebrae in
      adult sheep. In anaesthetised animals, radioactively labelled microspheres were
      injected into the left ventricle and blood withdrawn from the brachial artery.
      The lumbar spine was then removed and sectioned to measure microsphere
      deposition. Blood flow in the bony endplate was found to be 4.22 +/- 0.59 ml/min
      100 g, and flow of 0.57 +/- 0.29 ml/min 100 g was also measured in regions of the
      disc adjoining the endplate. No significant flow was recorded in the central
      region of the disc. This work has clinical significance in relation to spinal
      infections and also to the pathogenesis of degenerative disc disease.

PMID- 20058459
TI  - Mid-term effects of Cotrel-Dubousset instrumentation on the configuration of the
      spine and the thoracic cage in thoracic idiopathic scoliosis.
AB  - The effect of Cotrel-Dubousset instrumentation (CDI) on the three-dimensional
      spinal deformity in 24 consecutive patients with idiopathic scoliosis was
      investigated by posteroanterior and lateral radiographs and by computed
      tomography preoperatively, postoperatively, and at a mean follow-up of 3.2 years
      (range 2.0-5.3 years). At follow-up the mean Cobb angle was decreased by 73%, and
      the translation of the apical vertebra was significantly decreased by 33%. The
      sagittal contour was significantly improved with thoracic kyphosis T5-12
      increased by 46% (6.9 degrees) and lumbar lordosis L1-5 increased by 28% (10.3
      degrees) at follow-up. The sagittal diameter was significantly improved by 5 mm
      at follow-up. Although the vertebral rotation and the size of rib hump was
      improved postoperatively, this was followed by significant loss of correction,
      and at follow-up the vertebral rotation and the size of rib hump were not
      significantly better than preoperatively. The study indicates that while CDI
      improves the coronal and sagittal plane deformity permanently, the effect on
      vertetebral rotation and the rib hump deteriorates with time.

PMID- 20058461
TI  - Ossification of the transverse atlantoid ligament in rheumatoid arthritis.
AB  - Ossification of the transverse atlantoid ligament (TAL) is rare. A few cases have
      been reported by Wackenheim and Dietemann and others. Calcification of the TAL
      has also been seen in calcium pyrophosphate dihydrate deposition disease. It is
      important to differentiate this condition from traumatic lesions of the dens
      axis.

PMID- 20058460
TI  - Operative treatment of symptomatic lumbar spondylolysis and mild isthmic
      spondylolisthesis in young patients: direct repair of the defect or segmental
      spinal fusion?
AB  - Summary. The results of 23 patients with symptomatic spondylolysis or mild
      isthmic spondylolisthesis treated by Scott's direct repair of the defect
      (secclusion) were analyzed with particular reference to spinal mobility and the
      condition of the intervertebral discs, and compared with the outcome of 25
      patients treated by posterolateral segmental fusion without instrumentation. The
      two groups were comparable as to age at operation (17.4 +/- 5.7 vs. 15.6 +/- 2.6
      years), follow-up time (54 +/- 8 vs. 54 +/- 25 months), gender, and preoperative
      subjective symptoms. The mean preoperative vertebral slip was greater in the
      fusion group (7.2 +/- 8.4 vs. 13.1 +/- 4, P = 0.003). The follow-up assessment
      was carried out by an independent observer. It included an interview, Oswestry
      questionnaire, pain scale drawing, physical examination, plain radiographs,
      magnetic resonance imaging (MRI), and functional testing (lumbar spine mobility,
      static lifting power). For statistical analysis, the Student's t-test, the chi2
      test, and the paired t-test were used. At followup, 87% of the Scott's group and
      96% of the fusion group had occasional pain, not interfering with daily
      activities, or no pain at all. There was no statistical difference in the
      subjective, clinical, or functional outcome between the two operation groups.
      Plain radiographs in both groups showed significant loss of disc height in the
      operated segment during follow-up, indicating postoperative progression of disc
      degeneration. In flexion/extension radiographs the total range of movement in the
      three lowermost lumbar segments was slightly greater after secclusion. This
      difference was not significant. In MRI there was no statistical difference in
      disc hydration index between the two groups. The condition of the disc above the
      fusion was not worse than that of the corresponding disc above the secclusion.
      There was no correlation between pathologic disc findings in MRI and clinical
      outcome. It is concluded that in a small group of young patients the early
      results both after direct repair of the defect and after segmental fusion are
      satisfactory in the majority of cases. At this point of follow-up it is
      impossible to say which of the two procedures should be preferred for operative
      treatment of this condition in young patients. Direct repair does not protect the
      disc of the lytic/olisthetic segment from further degeneration. Pathologic disc
      changes in MRI should be interpreted with caution because their clinical
      relevance is still unclear.

PMID- 20058462
TI  - Strength reductions of thoracic vertebrae in the presence of transcortical
      osseous defects: effects of defect location, pedicle disruption, and defect size.
AB  - Transcortical osseous lesions were simulated in thoracic vertebrae to investigate
      the effects on vertebral strength of defect location, pedicle disruption, and
      defect size. Alternate vertebrae from 15 thoracic spines were assigned to five
      defect groups: anterior, posterior, lateral, one pedicle, or both pedicles. The
      remaining vertebrae served as controls. All vertebrae were tested to failure in
      combined axial-flexion loading. The intact failure load for each vertebra with a
      defect was estimated based on the actual failure loads of the control vertebrae
      from the same spine. The failure loads for vertebrae with transcortical defects
      (anterior, posterior, lateral) were significantly lower (P = 0.0001) than
      estimated intact loads; this was not the case for vertebrae with single pedicle
      disruption (P = 0.90). Relative strengths (defined as actual failure load divided
      by predicted intact failure load) for the anterior (mean = 0.51), posterior
      (0.55) and lateral (0.58) defect groups were not significantly different from
      each other, but were different from the single pedicle defect group (1.09).
      Relative strength depended only weakly on defect size. Comparison of these
      results with those of a previous study of simulated defects in the vertebral
      centrum suggests that transcortical defects result in slightly greater reductions
      in vertebral strength than defects of comparable size involving only trabecular
      bone.

PMID- 20058463
TI  - Enhanced prolylhydroxylase activity in the posterior annulus fibrosus of canine
      intervertebral discs following long-term running exercise.
AB  - The effect of long-term excercise on the intervertebral disc collagen
      concentration (hydroxyproline), collagen-synthesizing enzymes (prolyl-4
      hydroxylase, PH, and galactosyl-hydroxylysyl glucosyltransferase, GGT) and
      hydroxypyridinium crosslinks was studied in ten female beagle dogs. The dogs were
      run on a treadmill for 1 year starting at the age of 15 weeks. The daily running
      distance was gradually increased to 40km, which distance the dogs ran for the
      final 15 weeks. Ten untrained dogs from the same breeding colony served as
      controls. The nucleus pulposus and anterior and posterior halves of the annulus
      fibrosus of C2-3, T10-12, L4-5 disc segments were analysed. Crosslinks were
      measured from the anterior annulus fibrosus of the T10-11 disc. Hydroxyproline
      and hydroxypyridinium concentrations remained similar in both groups. PH and GGT
      were significantly elevated by running in the posterior annulus fibrosus of the
      thoracic and lumbar discs and in the lumbar nucleus pulposus. In the thoracic
      nucleus pulposus GGT was reduced significantly. The results suggest activated
      collagen metabolism in the posterior annulus fibrosus of the thoracic and lumbar
      discs as a result of locally increased strains on the spine.

PMID- 20058464
TI  - Urethral catheterization in spinal surgery: a randomized prospective study.
AB  - In a prospective randomized study the effect of the use of an intraoperative
      indwelling urethral catheter (IUC) on urinary complications was investigated in
      patients undergoing spinal fusion. Two groups were formed; 16 patients received
      an intraoperative IUC and 16 patients had no intraoperative catheter (NC). All
      patients were, if necessary, intermittently catheterized in the postoperative
      period. Seven of the patients in the IUC group had positive cultures, defined as
      > or = 100,000 CFU/ml, compared with two patients in the NC group (n.s.). Another
      four patients in the NC group had cultures > or =10000 CFU/ml. Thirteen patients
      in the IUC group and 14 patients in the NC group had positive dip slides. The
      largest received urine volume in each patient at one intermittent catheterization
      did not differ significantly between the groups. However, in three patients in
      the NC group the volumes exceeded 1000 ml. Thus, irrespective of treatment dip
      slides showed bacteriuria in 84% of the patients. Perioperative indwelling
      catheters do not seem to cause many more infection complications than no bladder
      drainage during surgery, and the advantages of reduced risk of bladder distension
      injury and more accurate monitoring of fluid balance suggest their use.

PMID- 20058465
TI  - Frequency of complications of manipulation of the spine. A survey among the
      members of the Swiss Medical Society of Manual Medicine.
AB  - A survey of all members of the Swiss Medical Association of Manual Medicine was
      undertaken for the year 1989. Informative data were given by 425 respondents on
      the frequency of complications of manipulation as related to the spine. The
      number of thoraco-lumbar manipulations during 1989 (225 working days) was 805 for
      each respondent, and the number manipulations of the cervical spine 354. Thus,
      the total number of thoraco-lumbar manipulations was 342125, and the total number
      of cervical manipulations was 150450. The overall incidence of side-effects of
      transient complications due to cervical spine manipulation such as disturbance of
      consciousness or radicular signs was 1:16716. Seventeen patients (ratio 1:20125)
      after manipulation of the lumbar spine presented, in addition to increased pain,
      a transient sensorimotor deficit with precise radicular distribution. Nine of the
      17 patients (ratio 1:38013) developed a progressive radicular syndrome with
      sensorimotor defict and radiologically verified disc herniation and had to be
      referred for surgery. Side effects and com- plications of cervical and lumbar
      spine manipulation are rare. Taking in to account the yearly number of
      manipulations performed by a single physician in Switzerland and the rate of
      complications, it can be calculated that a physician practicing manual medicine
      will encoutner one complication due to manipulation of the cervical spine in 47
      years and one complication due to lumbar spine manipulation in 38 years of
      practice. However, it is important that a careful clinical assessment is carried
      out to avoid complications due to manipulation carried out on the basis of
      inappropriate indications. Furthermore, the decision as to which technique is
      indicated for any particular functional disorder of the spine should be made on
      the basis of rational criteria resting on a knowledge of clinical biomechanics,
      functional anatomy and neurophysiology. The authors recommend a prospective
      morbidity study to be carried out among physicians, chiropractors, osteopaths and
      physiotherapists, taking into account the different indications and therapeutic
      techniques in relation to complications.

PMID- 20058466
TI  - A functional-anatomical approach to the spine-pelvis mechanism: interaction
      between the biceps femoris muscle and the sacrotuberous ligament.
AB  - Summary. Sacroiliac joint dysfunction is often overlooked as a possible cause of
      low back pain. This is due to the use of reductionistic anatomical models. From a
      kinematic point of view, topographic anatomical models are generally inadequate
      since they categorize pelvis, lower vertebral column and legs as distinct
      entities. This functional-anatomical study focuses on the question whether
      anatomical connections between the biceps femoris muscle and the sacrotuberous
      ligament are kinematically useful. Forces applied to the tendon of the biceps
      femoris muscle, simulating biceps femoris muscle force, were shown to influence
      sacrotuberous ligament tension. Since sacrotuberous ligament tension influences
      sacroiliac joint kinematics, hamstring training could influence the sacroiliac
      joint and thus low back kinematics. The clinical implications with respect to
      'short' hamstrings, pelvic instability and walking are discussed.

PMID- 20058467
TI  - Do augmentin or cefuroxime reach effective levels in lumbar vertebral discs when
      used prophylactically for discectomy? A preliminary report.
AB  - The incidence of discitis following discectomy is reported at between 0.75% and
      3.0%. We believe this rate could be reduced if an antibiotic that penetrated the
      disc tissue with an appropriate spectrum were to be given prophylactically to
      cover surgery. A prospective study of 20 patients undergoing routine lumbar
      discectomy was performed. Ten patients received Augmentin 1.2 g and ten received
      cefuroxime 1.5 g pre-operatively. In eight patients sequestrated disc fragments
      were analysed, and the majority were found to have drug levels higher than in the
      attached disc material; the reasons for this are discussed. We conclude that
      Augmentin penetrates damaged disc material to a limited extent, but cefuroxime
      achieves levels effective against the most commonly implicated pathogens in
      discitis tissue and is a rational choice of antibiotic for prophylaxis during
      lumbar discectomy.

PMID- 20058468
TI  - Lumbar discal herniation in the elderly: long-term results of chymopapain
      chemonucleolysis.
AB  - Very few reports in the literature have dealt with lumbar disc herniation in the
      elderly and its treatment by chymopapain chemonucleolysis. Between September 1981
      and May 1991, 42 patients aged between 60 and 80 years were treated by
      chemonucleolysis for lumbar disc herniation. The clinical symptoms and signs,
      similar to those observed in younger patients, were well correlated with a clear
      picture of discal herniation on the CT scan without any associated stenosis. At
      the last follow-up (mean 4.5 years) satisfactory results were obtained in 78% of
      the patients. No complication were observed. It is concluded that in the rare
      cases of discal herniation in the elderly, chymopapain chemonucleolysis should be
      considered as a safe and efficacious alternative to surgery.

PMID- 20058469
TI  - Long-term results after Harrington instrumentation: increased translation and
      pain.
AB  - Sixty-eight patients with idiopathic scoliosis who had undergone Harrington
      instrumentation at least 10 years previously (mean follow-up 14 years) were asked
      to return to our hospital for review. History and clinical examination were
      performed in 49 individuals (72%), radiographs in 44 individuals (64%). Pain was
      evaluated by means of the Dallas Pain Questionnaire and pain drawings according
      to Ransford. Segmental range of motion according to Begg and Falconer as well as
      sagittal translational motion measured according to Wiltse and Winter and to
      Morgan and King were evaluated in flexion/extension radiographs. Pain depended on
      fusion level. It occurred in 80% of those in whom fusion was carried down to L4
      or lower vertebrae. There was no relationship between fusion level or pain on the
      one hand and segmental range of motion or increased translation on the other
      hand, and none between lordosis, pain and increased translation. Increased
      sagittal translocational motion of more than the measurement error of 5 mm does
      not seem to be an important cause of pain in individuals in whom Harrington
      instrumentation was carried down to low vertebral levels.

PMID- 20058470
TI  - Reduction and stabilization of lumbar and thoracolumbar spine fractures with
      Louis' plates and internal fixator: a comparative study.
AB  - In this retrospective study, 28 patients who presented isolated fractures from
      T11 to L4 were surgically treated using a posterior approach. The fractures were
      reduced and stabilized in half of the cases with Louis' plates and in the other
      half with an internal fixator. Twelve patients had partial neurological deficits
      on admission. They were reviewed after a mean period of 24 months from time of
      injury, and 10 months after implant removal. The kyphosis of the fractured
      vertebral body was measured, and showed a mean value of 18 degrees before surgery
      and 10.3 degrees at the last visit. The regional statics of the spine were also
      studied. The residual mobility of the fixated and neighbouring spinal units was
      assessed, comparing "long" segment fixation (plates) with "sh ort" segment
      fixation (internal fixator). The residual mobility of the adjacent, non-fixed
      segments was significantly better when the internal fixator had been used than
      with the Louis' plates. Of the 12 patients with neurological involvement, 11 had
      increased their Frankel score by one grade. Results were evaluated by clinical
      parameters (pain, neurological deficit, occupational disability); scores were as
      follows: 32% good, 57% satisfactory and 11% poor. There was no significant
      difference in clinical score between the two treatment modalities.

PMID- 20058471
TI  - Comparison of epidemiology, methods, and results of treatment in cervical spinal
      injuries over the last 20 years in Poland.
AB  - This report presents a comparative analysis of two groups of patients with
      cervical spine injuries admitted to hospital in the early post-traumatic period,
      treated between 1965 and 1970 and between 1985 and 1990. The involvement of
      patients from rural and town areas equalized due mainly to the increased
      incidence of road accidents and decreased incidence of injuries following falls
      from a horse-cart. Wider implementation of surgical methods improved the outcomes
      and shortened the hospitalization time.

PMID- 20058472
TI  - Posterior spinal fusion of the cervical spine using the Alligator plate:
      operative technique and clinical results.
AB  - We have designed a new type of clamping plate called the "Alligator plate" for
      posterior cervical spinal fixation and used it in some cases with cervical
      instability. Seventeen patients with cervical instability treated by posterior
      cervical fixation using Alligator plate were clinically evaluated. As a control
      group, 21 patients treated by a wire fixation method (cerclage) were also
      evaluated. Clinical results were evaluated radiographically on dynamic flexion
      extension lateral radiographs with confirmation of the fusion mass on oblique
      view radiographs. The results of Alligator plate fixation were excellent in 15
      patients, good in one and poor in one. The results of wire fixation were
      excellent in 15 patients, good in three, fair in one and poor in two. A safe and
      simple alternative instrumentation, the Alligator plate has sufficient stability
      to be useful for treating instability of the lower cervical spine.

PMID- 20058473
TI  - Acute pericardial tamponade complicating spinal surgery in a child with Duchenne
      muscular dystrophy.
AB  - A hitherto unrecognised problem of pericardial tamponade complicating spinal
      surgery in a child with Duchenne muscular dystrophy is reported in this paper.

PMID- 20058474
TI  - Novel agents in the frontline management of multiple myeloma.
AB  - Significant advances in our understanding of the biology of multiple myeloma have
      led to exciting new opportunities in treatment. The management of this disease is
      rapidly changing with a plethora of clinical trials initiated with novel agents,
      namely thalidomide, lenalidomide and bortezomib, either alone or in conjunction
      with established modalities such as conventional cytotoxic agents and stem-cell
      transplantation. The combination of these novel agents together with conventional
      regimens have led to higher response rates and survival, providing options for
      patients whose disease is otherwise resistant to conventional therapy. These
      pivotal trials that lead to the approval of these three novel agents in treatment
      naive patients. The potential implications in the frontline treatment paradigm of
      multiple myeloma are discussed.

PMID- 20058475
TI  - Current and future cancer burden in Saudi Arabia: meeting the challenge.
AB  - BACKGROUND AND OBJECTIVES: Despite the low cancer incidence in Saudi Arabia, the
      country must be ready to face the challenge of a foreseeable increase in cancer
      burden mainly attributed to the growth and aging of the population. We designed
      this study to estimate the future cancer burden and to highlight the demands on
      prospective healthcare resources. METHODS: Cancer statistics in Saudi Arabia from
      2000 to 2004 were examined. The Joinpoint regression program was used to identify
      changes in secular trends, while the GLOBOCAN 2002 software projected future
      burden. Considering current trends and the growth and aging of the population, we
      projected the future burden. RESULTS: In 2004, the age-standardized rate (ASR)
      for incidence for all cancer sites, excluding basal and squamous skin cancer, was
      57.2 per 100000 (55.8 and 59.1 per in males and females, respectively). ASR
      trends showed a statistically significant increase in the annual percent change
      (APC) for both males and females, which was greatest from 2003 to 2004 (4.93% and
      2.64%, respectively). By the year 2020 and 2030, there would be an approximately
      6- and 10-fold rise among males as compared with the burden in 2004. The
      corresponding numbers for females would be 5- and 8-fold, respectively. The
      highest cancer burden would be expected for middle-aged and elderly Saudis.
      CONCLUSIONS: In countries currently experiencing low cancer rates, the future
      cancer burden could increase considerably and place enormous demands on
      healthcare resources. The present study may provide an impetus to examine the
      future all or site-specific cancer burden, particularly in developing countries.

PMID- 20058476
TI  - S-phase fraction as a useful marker for prognosis and therapeutic response in
      patients with aplastic anemia.
AB  - BACKGROUND: The functional definition of aplastic anemia (AA) is the failure of
      hematopoietic stem cells to proliferate. The aim of the present study was to
      analyze the S-phase fraction (SPF) (proliferative activity) in patients with AA
      at diagnosis to explore its relationship with disease characteristics and its
      value in discriminating among patients with different prognoses. We also
      investigated whether the SPF value influenced the response to immunosuppressive
      therapy in AA patients. PATIENTS AND METHODS: The analysis of SPF at the time of
      diagnosis was carried out by flow cytometry on peripheral blood samples from 53
      consecutive patients with AA and 30 age- and sex-matched controls. All patients
      were given cyclosporine and followed up periodically to determine response to
      therapy. RESULTS: Based on the median SPF, AA patients were divided into two
      groups: patients with SPF < 0.59% (n = 27) and patients with SPF > 0.59% (n =
      26). An SPF > 0.59% was associated with advanced age (P = .02) and elevated serum
      LDH level (P = .01). Patients with an SPF > 0.59% also had a higher incidence of
      paroxysmal nocturnal hemoglobinuria and cytogenetic abnormalities. During a
      median follow-up of 18 months, 3.7% of patients with SPF < or = 0.59 and 11.5% of
      patients with SPF > 0.59% developed dysplasia and one patient with SPF > 0.59%
      converted into AML. A significantly higher (P = .018) overall response rate of
      53.9% was found in patients with SPF > 0.59% versus 22.2% of patients with SPF <
      or = 0.59% at 6 months. CONCLUSIONS: Independently of the peripheral blood count,
      the SPF at diagnosis may provide information on the expected response to
      immunosuppressive therapy and the propensity for disease to evolve into MDS/AML.
      Hence, SPF may serve as an early indicator for the evolution of MDS/AML in
      patients with AA and thus contribute to therapeutic decisions.

PMID- 20058477
TI  - Gemcitabine/5-flourouracil/leucovorin for the treatment of advanced pancreatic
      carcinoma.
AB  - BACKGROUND AND OBJECTIVE: The response rate and median survival with gemcitabine
      monotherapy, although considered the standard treatment for inoperable and
      metastatic pancreatic cancer, is relatively poor. We tested the efficacy and
      toxicity of a chemotherapy protocol consisting of gemcitabine, 5-fluorouracil (5
      FU) and leucovorin in patients with inoperable or metastatic pancreatic cancer,
      which was shown to improve median survival in a small phase II trial. PATIENTS
      AND METHODS: Patients older than 18 years of age with histologically or
      cytologically confirmed adenocarcinoma of the pancreas and bidimensionally
      measurable disease, and who were chemotherapy- and radiotherapy-naive, were
      treated with a chemotherapy protocol consisting of gemcitabine 1250 mg/m2 on day
      1, 5-FU 450 mg/m2 and leucovorin 100 mg/m2 on days 1-3. The treatment was
      repeated every 2 weeks. RESULTS: In an-intention-to-treat analysis, of 37
      patients with pancreatic cancer (27 males, 10 females) (67.6% stage IVb) there
      were 7 (18.9%) objective partial responses (95% confidence interval, 8.33% to
      29), 14 (37.8%) patients had stable disease and 16 (43.2%) had progressive
      disease. The median response time was 3 months (range, 1.5 to 7.0 months). Median
      overall survival time was 6.5 months (range, 1.0 to 15.5 months). The response to
      chemotherapy was not different between males and females (P = .971). No grade
      III/IV toxicities were seen. CONCLUSION: Despite our poor survival data, the
      combination of gemcitabine with 5-/FU and leucovorin is an active and well
      tolerated regimen in patients with pancreatic cancer that merits further
      evaluation in prospective randomized studies. This combination may be considered
      a valuable alternative to gemcitabine alone.

PMID- 20058478
TI  - Biological features and outcome of biphenotypic acute leukemia: a case series.
AB  - BACKGROUND: Biphenotypic acute leukemia (BAL) is a distinct entity that is
      immunophenotypically defined by the European Group for the Immunological
      Classification of Leukemia (EGIL) scoring system and accounts for less than 5% of
      all acute leukemia cases. Since it is a rare and heterogeneous form of acute
      leukemia with an allegedly poor outcome, there is no consensus on the best
      treatment approach in these patients. Our objective was to analyze the biological
      features and outcome of patients diagnosed with BAL in our institution. PATIENTS
      AND METHODS: Using the EGIL system, we identified 21 cases (3.9%) of BAL from 535
      newly diagnosed acute leukemia patients in an 11-year period. RESULTS: There were
      ten cases of myeloid+B-lymphoid leukemia, eight cases of myeloid+T-lymphoid, one
      case of B+T-lymphoid and two cases of trilineage (myeloid+B+T-lymphoid leukemia).
      The complete remission (CR) rate with high-dose chemotherapy was 72% and overall
      survival at 5 years was 21%. Patients that received acute lymphoblastic leukemia
      oriented chemotherapy had a higher CR rate compared with those who received acute
      myeloid leukemia-oriented chemotherapy (100% vs. 60%, P = .007). The white blood
      cell count at diagnosis was found to have statistically significant impact on
      survival. CONCLUSION: Despite the progress in the treatment of acute leukemia,
      the prognosis of BAL remains poor and treatment protocols devised explicitly for
      this entity should be investigated in prospective collaborative studies.

PMID- 20058479
TI  - Hematopoietic stem cell transplantation in Iran: 1991 to 2008.
AB  - Since 1991, 2042 first hematopoietic stem cell transplants (HSCT) have been
      performed at the Hematology-Oncology and Stem Cell Transplantation Research
      Center at Tehran University of Medical Sciences. Acute myelogenous leukemia (548
      patients), thalassemia major (335 patients) and acute lymphoblastic leukemia (275
      patients) have been the most common transplanted disorders. There were 1418 cases
      that received allogeneic HSCT and 624 cases that have received autologous HSCT.
      The numbers of allogeneic and autologous HSCT have increased, but the allogeneic
      to autologous ratio has remained constant. The first peripheral blood
      hematopoietic stem cell transplantation was performed in 1996; since then, 1671
      have been done. The donor types for 1418 allogeneic first HSCT were 1367 (96.4%)
      human leukocyte antigen (HLA) matched-identical siblings, 29 (2%) HLA-mismatched
      sibling/other relative, 13 (0.9%) syngeneic twins, 5 (0.4%) HLA-matched other
      relatives and 4 (0.3%) unrelated. The first cord blood hematopoietic stem cell
      transplantation was performed in 1998 and since then there have been 14 patients
      that have obtained cord blood transplantations. Recently, new methods have been
      used like donor lymphocyte infusion (DLI) and cellular therapy. There were 111
      patients with cellular therapy for post-myocardial infarction, cirrhosis,
      thalassemia major, multiple sclerosis, head of femur necrosis and renal cell
      carcinoma.

PMID- 20058480
TI  - Stabilization of acute myeloid leukemia with a dendritic cell vaccine.

PMID- 20058481
TI  - Extramedullary plasmacytoma: clinicopathology, immunohistochemistry and
      therapeutic approach to a case with a tonsillar site.

PMID- 20058482
TI  - Primary malignant melanoma of the esophagus.

PMID- 20058483
TI  - Choroid and cutaneous metastasis from a testicular tumor.

PMID- 20058484
TI  - SiRNA silencing efficacy prediction using the RNA string kernel.
AB  - While most existing string kernels are developed for general purpose sequences
      and have been applied to text and protein classifications, the RNA string kernel
      is particularly designed to model mismatches, G-U wobbles, and bulges of RNA
      biology. We adapt the RNA kernel to compute the similarity of the short
      interfering RNAs (siRNAs), initiators of RNA interference, and use it in support
      vector regression to predict the siRNA silencing efficacy treated as a continuous
      variable. Empirical results on biological data sets demonstrate that the RNA
      string kernel performed favourably. In addition, it is simple to implement and
      fast to compute.

PMID- 20058485
TI  - CLUSS2: an alignment-independent algorithm for clustering protein families with
      multiple biological functions.
AB  - CLUSS is an algorithm proposed for clustering both alignable and non-alignable
      protein sequences. However, CLUSS tends to be ineffective on protein datasets
      that include a large number of biochemical activities. To overcome this
      difficulty, we propose in this paper a new algorithm, named CLUSS2 that scales
      better with the increase of the number of biochemical activities. CLUSS2 differs
      from CLUSS in many ways including protein sequences representation, conserved
      motifs extraction and time efficiency. Our experiments show that CLUSS2 more
      accurately highlights the functional characteristics of the clustered families,
      especially for those with a large number of biochemical activities.

PMID- 20058486
TI  - Poisson approach to clustering analysis of regulatory sequences.
AB  - The presence of similar patterns in regulatory sequences may aid users in
      identifying co-regulated genes or inferring regulatory modules. By modelling
      pattern occurrences in regulatory regions with Poisson statistics, this paper
      presents a log likelihood ratio statistics-based distance measure to calculate
      pair-wise similarities between regulatory sequences. We employed it within three
      clustering algorithms: hierarchical clustering, Self-Organising Map, and a self
      adaptive neural network. The results indicate that, in comparison to traditional
      clustering algorithms, the incorporation of the log likelihood ratio statistics
      based distance into the learning process may offer considerable improvements in
      the process of regulatory sequence-based classification of genes.

PMID- 20058487
TI  - A bottom-up approach to the biclustering-problem.
AB  - The biclustering problem adresses the discovery of locally significant
      correlation within a data matrix and has recently become quite popular in the
      field of microarray data analysis. The preservation of a particularly defined
      degree of homogeneity between elements within a bicluster plays a key role in the
      search procedure. This work proposes a pairwise distance function related to the
      mean squared residue to introduce multiple enrichment algorithms. Based on a
      theoretical framework, the impact is demonstrated empirically by the enrichment
      of commonly available and also on artificially generated bicluster sets.

PMID- 20058488
TI  - BioTDMS: a general-purpose system for integrative management of bioinformatics
      tools and data.
AB  - Proper management of bioinformatics data and tools is crucial because the amount
      of data is enormous, the type of data varies, and there are often different
      approaches (and consequently tools) for solving a particular problem. While
      specialised systems exist to serve specific needs, such systems are difficult to
      adapt and require large resource commitments for development and maintenance. We
      propose a system called Bioinformatics Tools and Data Management System (BioTDMS)
      that uses open-source technologies to provide a platform for managing both data
      and tools. We present case studies that show some potential applications of this
      system.

PMID- 20058489
TI  - A motif extraction algorithm based on hashing and modulo-4 arithmetic.
AB  - We develop an algorithm to identify cis-elements in promoter regions of
      coregulated genes. This algorithm searches for subsequences of desired length
      whose frequency of occurrence is relatively high, while accounting for slightly
      perturbed variants using hash table and modulo arithmetic. Motifs are evaluated
      using profile matrices and higher-order Markov background model. Simulation
      results show that our algorithm discovers more motifs present in the test
      sequences, when compared with two well-known motif-discovery tools (MDScan and
      AlignACE). The algorithm produces very promising results on real data set; the
      output of the algorithm contained many known motifs.

PMID- 20058490
TI  - BIPASS: design of alternative splicing services.
AB  - We analyse the motivations that led the development of services to support
      alternative splicing studies. We discuss data modelling issues and illustrate
      them with the BioInformatics Pipeline for Alternative Splicing Services (BIPASS).
      We identify the specific needs that an alternative splicing service should
      address, and compare existing services with respect to a common matrix of
      functionalities. We conclude with a discussion on future work needed to offer a
      more complete suite of services.

PMID- 20058491
TI  - MGMA advocacy on healthcare reform: an update.

PMID- 20058492
TI  - Watch your site-of-service coding. OIG identifies high error rate.

PMID- 20058493
TI  - Is it unethical not to use an EHR?

PMID- 20058494
TI  - The new privacy-breach notification rule. What you need to know to prepare your
      practice.

PMID- 20058495
TI  - Efficient, enterprising, electronic. Pediatric group stays current with
      technology.

PMID- 20058496
TI  - Howdy, partner! How your practice can team up with hospitals to recruit
      physicians.

PMID- 20058497
TI  - Got authority? An administrator needs to know scope of power.

PMID- 20058498
TI  - The physician-administrator team. Still an optimal model for leading medical
      practices.

PMID- 20058499
TI  - Clinical integration is back. How you can take charge in the quality-driven
      health reform environment.

PMID- 20058500
TI  - A fix for multiple database billing. Meet a key challenge of mergers and
      acquisition.

PMID- 20058501
TI  - Atherothrombosis: a vanishing disease?

PMID- 20058502
TI  - A long-term comparison of drug-eluting versus bare metal stents for the
      percutaneous treatment of coronary bifurcation lesions.
AB  - BACKGROUND: After the first exciting results on drug-eluting stents (DES), many
      concerns have been raised on their potential risk for late stent thrombosis.
      Whereas DES appear beneficial at early and mid-term for coronary bifurcation
      lesions, no data are available on their long-term safety in this setting in
      comparison to bare metal stents (BMS). We thus aimed to appraise the long-term (>
      2 years) outcomes of patients with bifurcation lesions treated with DES vs. BMS.
      METHODS: We abstracted baseline, procedural and follow-up data on all patients
      with bifurcation coronary lesions (both branches with reference vessel diameter >
      2.0 mm) treated with stent implantation at our centre. The primary end-point was
      the long-term (> 2 years) rate of major adverse cardiac events (MACE, i.e.
      cardiac death, myocardial infarction, coronary artery bypass grafting and target
      vessel revascularization). RESULTS: A total of 315 patients and 334 lesions were
      included, 84.4% treated with DES, and 15.6% treated with BMS. The side branch was
      stented in 108 cases, according to a provisional T in 76 (22.7%), crushing in 15
      (4.5%),V in 14 (4.2%), and culottes in 1 (0.3%). In-hospital MACE occurred in 4
      (1.5%) patients of the DES group and 2 (4.1%) of the BMS group (P = 0.22). After
      35.8 +/- 12.9 months, MACE were 72 (27.1%) vs. 24 (49%), respectively (P =
      0.002), with cardiac death in 7 (2.6%) patients vs. 3 (6.1%, P = 0.20),
      myocardial infarction in 12 (4.5%) vs. 6 (12.2%, P = 0.42), coronary artery
      bypass grafting in 5 (1.9%) vs. 1 (2%, P = 0.93), target lesion revascularization
      in 30 (11.3%) vs. 13 (26.5%, P = 0.0042), and target vessel revascularization in
      48 (18%) vs. 13 (26.5%, P = 0.16). Definite stent thrombosis occurred in 2
      (0.75%) patients in the DES group vs. 1 (2%, P = 0.93) in the BMS group, whereas
      probable stent thrombosis was adjudicated in 5 (1.9%) vs. 2 (4%, P = 0.93).
      CONCLUSION: This cohort study, reporting for the first time on the long-term
      outlook of patients treated with DES vs. BMS for coronary bifurcation lesions,
      supports the overall safety and efficacy of DES in comparison to BMS.
      Specifically, even after several years of follow-up, repeat revascularizations
      appeared significantly lower with DES, and stent thromboses occurred with
      equivalent frequency in both DES and BMS groups.

PMID- 20058503
TI  - Decrease in plasma brain natriuretic peptide level in the early phase after the
      start of carvedilol therapy is a novel predictor of long-term outcome in patients
      with chronic heart failure.
AB  - OBJECTIVE: The purpose of the present study was to determine whether change in
      plasma brain natriuretic peptide (BNP) level at an early phase of carvedilol
      therapy is a predictor of improvement in cardiac function and long-term prognosis
      in patients with systolic chronic heart failure (CHF). METHODS AND RESULTS:
      Neurohumoral factors and haemodynamics were examined in 64 patients with systolic
      CHF (left ventricular ejection fraction (LVEF) below 45%) before and one month
      (early phase) and 3 to 6 months (late phase) after the start of carvedilol
      therapy. These patients were followed up for a mean period of 57 months. Plasma
      BNP levels were already decreased in the early phase before improvement of LVEF
      in response to carvedilol therapy. Univariate and multivariate linear regression
      analyses showed that Delta log brain natriuretic peptide (BNP)E (= log BNP at
      baseline--log BNP at early phase) (P < 0.0001) was a significant independent
      predictor of improvement in LVEF in the late phase. Cardiac events occurred in I
      I patients during the follow-up period. In addition, multivariate Cox
      proportional hazards regression analysis showed that Delta log BNPE (P = 0.0045)
      and systolic blood pressure at baseline (P = -0.048) were significant independent
      predictors of the development of cardiac events. CONCLUSIONS: Decrease in plasma
      BNP level in the early phase of carvedilol therapy is a novel predictor of not
      only improvement of LVEF in the late phase but also prognosis in patients with
      systolic CHF.

PMID- 20058504
TI  - Impaired aortic elasticity in patients with psoriasis.
AB  - BACKGROUND: Psoriasis vulgaris is a chronic inflammatory disease involving 1-3%
      of the human population worldwide. Many systemic diseases including
      cardiovascular disturbances have been described in psoriatic patients. The effect
      of psoriasis on aortic elasticity parameters has not been well-defined
      previously. The aim of this study was to determine whether there was any change
      in aortic elasticity in psoriasis. METHODS: Twenty-seven psoriatic patients
      without cardiovascular involvement and 22 healthy subjects were enrolled into the
      study. The severity of the disease was evaluated by the "Psoriasis Area and
      Severity Index (PASI)". Aortic strain, distensibility and stiffness index were
      calculated from aortic diameters measured by echocardiography and blood pressures
      simultaneously measured by sphygmomanometry. RESULTS: The aortic strain and
      distensibility in the psoriasis group were significantly lower than those in the
      control group. The aortic stiffness index in the psoriasis group was higher than
      that in the control group. There was a positive correlation between aortic
      stiffness index and PASI and longevity of psoriasis disease, whereas a negative
      correlation between aortic strain and PASI and longevity of psoriasis disease was
      found. CONCLUSION: We found that in psoriatic patients without cardiac
      involvement, aortic elasticity was decreased and this decrease was correlated
      with the duration and the severity of the disease.

PMID- 20058505
TI  - Levels of proinflammatory cytokines and hs-CRP in patients with homozygous
      familial hypercholesterolaemia.
AB  - OBJECTIVE: Homozygous familial hypercholesterolemia (FH) is an extremely rare
      (1/1,000,000) condition characterized by markedly increased LDL cholesterol
      levels and a significantly increased risk of premature coronary heart disease
      (CHD). We aimed to evaluate the levels of high-sensitivity C-reactive protein (hs
      CRP) and proinflammatory cytokines, which are known to be associated with
      atherogenesis, in patients with this condition. METHOD AND RESULTS: A total of 10
      patients with homozygous FH (5 women and 5 men, mean age 17.0 +/- 6.9 years, body
      mass index (BMI) (18.8 +/- 1.9 kg/m2) and 16 healthy controls were included. hs
      CRP levels, proinflammatory cytokine levels and lipid parameters were measured
      and compared between patients and control subjects. Homozygous FH patients had
      significantly higher total cholesterol, LDL-cholesterol and Lp(a) levels and
      significantly lower triglyceride and HDL cholesterol levels, compared to controls
      (P = 0.0001, for all). Serum hs-CRP (3.7 +/- 1.3 mg/L vs. 0.6 +/- 0.6 mg/L) and
      IL-1beta, IL-2R, IL-6, IL-8, IL-10, TNF-alpha levels were all significantly
      higher in the homozygous FH group, compared to controls (P = 0.0001, for all).
      CONCLUSIONS: Homozygous FH patients have significantly higher levels of hs-CRP
      and circulating proinflammatory cytokines, which may explain their increased risk
      of atherosclerotic disease. hs-CRP is an important biomarker that may be helpful
      in the identification of asymptomatic CHD in FH patients.

PMID- 20058506
TI  - Post-intervention IVUS is not predictive for very late in-stent thrombosis in
      drug-eluting stents.
AB  - OBJECTIVES: Stent thrombosis is a life-threatening complication associated with
      sudden death and acute myocardial infarction. Histopathologic studies have linked
      the occurrence of very late stent thrombosis in drug-eluting stents (DES) with
      delayed endothealisation and stent malapposition. Our aim was to investigate if
      late stent malapposition in DES could be predicted by immediate postintervention
      intra-vascular ultrasonography (IVUS). METHODS AND RESULTS: From our MISSION!
      database of 184 consecutive patients with ST-elevation myocardial infarction
      (STEMI) who had immediate post-intervention and nine-month follow-up IVUS
      examinations we prospectively identified three patients with very late (> 365
      days) and definite (with angiographic evidence) in-stent thrombosis in DES.
      Patients had completed the twelve-month clopidogrel-aspirin dual treatment
      period, two of them were under aspirin therapy while the third patient had
      aspirin temporarily discontinued before planned surgery. When assessed by serial
      documentary (immediate post-intervention and nine-month) IVUS, all three patients
      demonstrated stent malapposition at nine months: in two cases the malapposition
      was acquired (immediate post-intervention IVUS showed a well apposed stent) and
      one case presented persistent malapposition (the stent was found malapposed both
      at immediate post-intervention and nine-month follow-up IVUS). CONCLUSIONS:
      Immediate post-intervention IVUS showing no malapposition does not guarantee an
      uneventful course after DES implantation.

PMID- 20058507
TI  - Masked diastolic dysfunction caused by exercise testing in hypertensive heart
      failure patients with normal ejection fraction and normal or mildly increased LV
      mass.
AB  - INTRODUCTION: It is not clear whether in patients with the clinical suspicion of
      heart failure with normal ejection fraction (HFNEF) exercise assessment of
      diastolic function may help to unmask abnormalities not detected by resting
      measurements. METHODS AND RESULTS: A combined radionuclide angiographic and
      haemodynamic exercise study was performed to confirm definite diastolic
      dysfunction in hypertensive patients with exertional dyspnoea and no other
      detectable cause of their symptoms. Only patients with normal baseline left
      ventricular (LV) systolic and diastolic function parameters as evaluated by
      routine cardiac catheterization and transmitral Doppler echocardiography were
      accepted (n = 38). All parameters were compared to a control group (n = 10).
      Twenty-eight patients showed an abnormal elevation in pulmonary capillary wedge
      pressure with exercise. As a consequence of a reduced exercise stroke volume (58
      +/- 13 vs. 70 +/- 12 ml/m2; P = 0.01) peak cardiac output was reduced in HFNEF
      (9.3 +/- 1.7 vs. 7.6 +/- 2.0 l/min/m2; P = 0.02). These changes were equally
      demonstrable in patients with and without ventricular hypertrophy. LV end
      systolic wall stress (ESWS) was increased at rest and during exercise in HFNEF
      patients without hypertrophy. However, a positive relationship between ESWS and
      the corresponding exercise stroke volume (r = 0.57; P = 0.002) was observed in
      the entire HFNEF group. CONCLUSION: Detection of diastolic dysfunction in
      suspected HFNEF is not only a question of the diagnostic methods used, but of the
      conditions under which the patients are investigated.

PMID- 20058508
TI  - Angiographic characteristics of major intramural coronary arteries and their
      effect on coronary bypass surgery.
AB  - OBJECTIVE: Dissection of intramyocardial coronary arteries can cause technical
      problems in coronary bypass surgery, including bleeding and inadvertent
      ventricular perforation, which can prolong the operation time. The goal of this
      study was to assess the effects of intramural coronary arteries on coronary
      bypass surgery and to define the angiographic characteristics of these coronary
      arteries. METHODS AND RESULTS: We studied 112 patients (60.12 +/- 10.23 y, 98 M)
      who underwent coronary bypass surgery, half of whom had intramural coronary
      arteries. Coronary angiographies were revised just after surgery, and
      characteristics of intramural coronary arteries were documented by combining
      surgical findings and angiographies. In angiographic examinations, studied
      intramural segments of the coronary arteries had less angulations in contrast to
      matched segments of control groups (mean 1.1 +/- 0.3 vs. 2.46 +/- 1.04, P <
      0.001), and the angles were significantly smaller (13.25 +/- 1.28 degrees vs.
      24.11 +/- 11.0 degrees P < 0.001). During surgery the intramural portions of the
      coronary arteries appeared to be free of atherosclerotic plaques. Mean cross
      clamp time of patients with intramural coronary arteries was longer than that in
      control patients (58.86 +/- 19.65 vs. 48.29 +/- 16 68, P < 0.01). CONCLUSIONS:
      Major intramural coronary arteries can be diagnosed preoperatively by
      angiographic examination. Overlying myocardial bands play a protective role
      against coronary artery atherosclerosis.

PMID- 20058509
TI  - Does time delay between the primary cardiac arrest and PCI affect outcome?
AB  - OBJECTIVES: In patients with acute ST-segment elevation acute myocardial
      infarction (AMI), no data are available on the prognostic value of cardiac arrest
      (CA) due to ventricular fibrillation (VF) before, during, and after percutaneous
      coronary intervention (PCI). The aim of our study was to determine differences in
      prognosis between patients with CA before, during, and after PCI. METHODS: Among
      448 patients with first ST-segment elevation AMI, we selected 34 (7.6%) with
      primary CA due to VF and 6 (1.3%) with secondary CA. The patients with primary CA
      were categorized into groups according to the time of the first episode of the
      primary CA, either before [12 (35.3%)], during [18 (52.9%)], or after [4 (11.8%)]
      PCI procedure. The 30-day all-cause mortality rate was analysed. RESULTS: Short
      term mortality was: (i) in patients without CA: 7.1% (29/408); (ii) in patients
      with primary CA 35.3% (12/34); (iii) in patients with secondary CA 50% (3/6); (P
      < 0.001). Mortality was 8.3% (1/12) in patients with primary CA before PCI; 44.4%
      (8/18) in patients with primary CA during PCI; 75% (3/4) in patients with primary
      CA after PCI procedure; (P = 0.007). CONCLUSIONS: Patients with a primary CA have
      the same poor prognosis as patients with a secondary CA. The prognosis worsened
      according to the time of the occurrence of the primary CA. It might be reasonable
      to isolate subgroups of ST-segment elevation AMI patients treated with PCI with
      primary CA according to time of primary CA. This could help to better stratify
      the risk of these patients.

PMID- 20058510
TI  - Reduction of cardiovascular event rate: different effects of cardiac
      rehabilitation in CABG and PCI patients.
AB  - OBJECTIVE: In coronary artery disease, the implementation of a cardiac
      rehabilitation (CR) programme favourably affects cardiovascular prognosis.
      However, it remains uncertain whether patients benefit to a similar extent from
      CR after coronary artery bypass graft surgery (CABG) or percutaneous coronary
      intervention (PCI). In this study, we have assessed whether CR is equally
      effective for suppressing the two-year cardiovascular event incidence after CABG
      or PCI. METHODS AND RESULTS: 194 PCI and 149 CABG patients participated in a
      three-month CR programme, while 245 PCI and 89 CABG patients received standard
      care. After the completion of CR during a two-year follow-up, data on
      cardiovascular risk factors, medication and cardiovascular events (repeat
      coronary revascularisation, acute myocardial infarction, and death) were
      collected from hospital files. Both CABG and PCI patients included into CR showed
      a significantly lower mortality, as compared to control patients (0.6% vs. 4.2%,
      P < 0.05). However, total cardiovascular disease incidence was significantly
      lower as a result of CR in CABG patients (4.7% vs. 14.0%, P < 0.05), but not in
      PCI patients (19.1% vs. 22.4%, P > 0.05). CONCLUSION: When following a similar 3
      month cardiac rehabilitation programme, the reduction of cardiovascular disease
      incidence during 2 years of follow-up is different between PCI and CABG patients.

PMID- 20058511
TI  - Aortic root dilatation is associated with carotid intima-media thickness but not
      with carotid plaque in hypertensive men.
AB  - BACKGROUND: The role of atherosclerosis-related processes in aortic root
      dilatation (ARD) has not been fully determined. The present study was to assess
      the relationship between carotid IMT, carotid plaque, and ARD. METHODS:
      Hypertensive men with ARD (n = 30) were compared with hypertensive men without
      ARD (n = 52) and normal control subjects (n = 29). Two-dimensional
      echocardiography was used to measure the aortic root at the aortic annulus, the
      sinus of Valsalva, the sinotubular junction and the proximal part of the
      ascending aorta. Carotid IMT and carotid plaque were also assessed by ultrasound.
      RESULTS: The measured mean carotid IMT was significantly increased in patients
      with ARD (1.37 +/- 0.80 mm) compared to the subjects without ARD (1.06 +/- 0.54
      mm) and healthy control subjects (0.84 +/- 0.44 mm) (P < 0.05). However, no
      significant differences of the prevalence of carotid plaque were found in the
      three groups (P > 0.05). Aortic diameters at all levels except for the diameter
      of the supra-aortic ridge were significantly related to carotid IMT when the
      hypertensive population was considered (P < 0.05). No significant correlation was
      found between carotid plaque and aortic root dimension (P > 0.05). CONCLUSION:
      This study shows that carotid intima-media thickening, but not carotid
      atherosclerotic plaque, is positively associated with ARD. Further studies to
      explore the underlying mechanism are awaited.

PMID- 20058512
TI  - Chronic aortic dissection: still a challenge.
AB  - Chronic aortic dissections are complex lesions with a fairly predictable natural
      history depending on factors such as baseline aortic diameter, the degree of
      false lumen thrombosis, the presence of a persistent communication, an underlying
      connective tissue disorder, and the control of hypertension. Medical management
      with antihypertensive therapy including beta-blockers is the treatment of choice
      for all stable chronic aortic dissections. Repair is indicated in the case of
      complications: aortic rupture, malperfusion syndromes, symptomatic dissections,
      asymptomatic dissections becoming significantly aneurysmal or demonstrating a
      rapid growth rate. In this regard, serial imaging of the aorta is crucial to
      detect unstable lesions requiring surgery or an endovascular intervention. As
      endograft technologies improve endovascular approach may become the future
      standard of care.

PMID- 20058513
TI  - Novel use of a subcutaneous shock lead to create an epicardial implantable
      cardioverter/defibrillator system via a limited thoracotomy.
AB  - We report the case of a novel use of a subcutaneous shock lead to create an
      epicardial implantable cardioverter/defibrillator (ICD) system via a limited
      thoracotomy in a patient with poor vascular access. Performance of the system is
      comparable to the conventional ICD system without the disadvantages of other
      available epicardial ICD systems.

PMID- 20058514
TI  - Angina pectoris as first manifestation of a huge biatrial myxoma.
AB  - A 73-year-old woman with a history of atrial fibrillation suffered from
      exertional chest pain and discrete dyspnoea. Cardiac catherization showed a
      vascular malformation in the atria, fed from vessels of the circumflex and left
      descending coronary artery. Echocardiography detected a biatrial tumour (13.7 x
      9.7 cm). The tumour mass was completely removed and histologic examination
      revealed a biatrial myxoma with extensive vascular lesions which apparently
      induced angina by coronary steal effect.

PMID- 20058515
TI  - Pericarditis with massive pericardial effusion in a cytomegalovirus-infected
      infant.
AB  - We report a case of pericarditis with massive pericardial effusion in a female
      infant with cytomegalovirus (CMV) infection. Viral infection is a common cause of
      acute myocardial and pericardial disease; most of these patients are infected
      with enterovirus and are asymptomatic. Cardiac involvement in CMV infection is
      rare, with CMV-related pericarditis being reported mainly in patients who were
      immunocompromised as a result of autoimmune deficiency syndrome (AIDS) or organ
      transplantation. This paper describes a 3.5-month-old breastfed infant girl with
      a healthy history, who presented with CMV infection.

PMID- 20058516
TI  - Heart failure in a patient with corrected transposition of the great arteries.
      When is biventricular pacing indicated?
AB  - This report presents a patient with complex congenitally corrected transposition
      of the great arteries (ccTGA) and concomitant ventricular septal defect (VSD),
      who developed symptomatic heart failure further aggravated after dual-chamber
      pacemaker implantation. The initial disqualification from surgery based on high
      vascular pulmonary resistance was verified in repeated catheterization. The
      oxygen test was positive, therefore the patient underwent surgical correction.
      Despite successful repair with the use of two prosthetic valves (mechanical and
      biological) and an intraventricular patch, the symptoms of heart failure
      persisted. In view of the prolonged QRS complex on the ECG and the signs of
      significant intraventricular mechanical dyssynchrony measured by Tissue Doppler
      Imaging (TDI), the patient was referred for cardiac resynchronization therapy
      (CRT). A biventricular pacemaker allowed a larger synchronicity of systemic RV
      systolic function and the improvement of the patient's general condition. The
      case described indicates that optimal care in patients with ccTGA can require
      implementation of both surgical and electrophysiological methods of treatment.

PMID- 20058517
TI  - Intimal sarcoma of the pulmonary artery: a report of two cases.
AB  - Intimal sarcoma of the pulmonary artery (PAS) is a rare but potentially lethal
      tumour, frequently misdiagnosed as chronic thrombo-embolic pulmonary artery
      disease. Despite the availability of advanced imaging technologies, its
      preoperative diagnosis remains difficult. We report on two patients with clinical
      features mimicking chronic pulmonary thrombo-embolism. Further discussion will
      focus on the differential diagnosis with more classical causes of obstructive
      pulmonary vascular disease.

PMID- 20058518
TI  - Electrical storm in a patient with dilated non-ischaemic cardiomyopathy.
AB  - Bundle-branch re-entrant ventricular tachycardia (BBRVT) is usually seen in
      patients with dilated cardiomyopathy. The diagnosis should be suspected in case
      the QRS morphology during the tachycardia is identical to that in sinus rhythm.
      Identifying patients with BBRVT is important because they can be easily treated
      by catheter ablation. This report describes a patient previously implanted with a
      cardiac resynchronization therapy defibrillator (CRT-D) presenting with an
      electrical storm due to BBRVT.

PMID- 20058519
TI  - Cryptogenic stroke in the presence of venous bronchopulmonary collateralisation.
AB  - We report the case of a 37-year-old man with a history of Hodgkin lymphoma and
      paroxysmal atrial fibrillation, seen because of a transient ischaemic attack with
      symptoms of temporary aphasia. Transoesophageal echocardiography could not detect
      a patent foramen ovale. However, CT thorax and flebography showed bilateral
      occlusion of both subclavian veins and the superior vena cava with an important
      collateral venous network, most likely responsible for this rare case of acquired
      cryptogenic stroke.

PMID- 20058520
TI  - Spontaneous jugular vein thrombosis.
AB  - Jugular vein thrombosis (JVT) is usually secondary to central venous
      catheterisation, distant malignancy, hypercoagulable state or ovarian
      hyperstimulation syndrome. Spontaneous internal JVT is an extremely rare entity.
      A 61-year-old man presented with swelling of the right side of his face. An
      ultrasonographic scan showed thrombosis of the right jugular vein. Clinical
      tests, including oncomarkers, X-ray, CT scan and abdominal ultrasonography,
      searching for malignancy, were negative. The patient was heparinized immediately
      using LMWH and then underwent warfarin anticoagulation therapy for 6 months. One
      year later the patient was in good clinical condition with no malignancy
      diagnosed. Aetiology and the treatment of spontaneous JVT are discussed.

PMID- 20058521
TI  - Noninvasive evaluation of a coronary-pulmonary artery fistula.
AB  - Coronary angiography can be used to identify the size and anatomical features of
      coronaryartery fistulas (CAF), but it may fail to depict the drainage site of the
      CAF or its relation to other structures. In our case, the combined use of CT and
      CMR provided all the necessary information forclinical management.

PMID- 20058522
TI  - Twiddling with an implantable cardioverter-defibrillator.
AB  - A 64-year-old woman underwent implantation of a single-chamber implantable
      cardioverter-defibrillator. The active fixation lead was positioned in the right
      ventricular apex and the generator in a left pre-pectoral pocket. Device
      interrogation 4weeks after implantation revealed inappropriate sensing and
      failure of pacing. A chest X-ray showed the entire lead coiled behind the device.
      The patient admitted manipulating the device and a diagnosis of Twiddler's
      syndrome was made. After repositioning the lead, the generator was re-located in
      the sub-pectoral position to help prevent recurrence by reducing the ability to
      externally manipulate the device.

PMID- 20058523
TI  - Health emergency & care management.

PMID- 20058524
TI  - A computational approach for the health care market.
AB  - In this work we analyze the market for health care through a computational
      approach that relies on Kohonen's Self-Organizing Maps, and we observe the
      competition dynamics of health care providers versus those of patients. As a
      result, we offer a new tool addressing the issue of hospital behaviour and demand
      mechanism modelling, which conjugates a robust theoretical implementation
      together with an instrument of deep graphical impact.

PMID- 20058525
TI  - Incentive compatibility in kidney exchange problems.
AB  - The problem of kidney exchanges shares common features with the classical problem
      of exchange of indivisible goods studied in the mechanism design literature,
      while presenting additional constraints on the size of feasible exchanges. The
      solution of a kidney exchange problem can be summarized in a mapping from the
      relevant underlying characteristics of the players (patients and their donors) to
      the set of matchings. The goal is to select only matchings maximizing a chosen
      welfare function. Since the final outcome heavily depends on the private
      information in possess of the players, a basic requirement in order to reach
      efficiency is the truthful revelation of this information. We show that for the
      kidney exchange problem, a class of (in principle) efficient mechanisms does not
      enjoy the incentive compatibility property and therefore is subject to possible
      manipulations made by the players in order to profit of the misrepresentation of
      their private information.

PMID- 20058526
TI  - Tactical and operational decisions for operating room planning: efficiency and
      welfare implications.
AB  - In this paper, we evaluate the impact on welfare implications of a 0-1 linear
      programming model to solve the Operating Room (OR) planning problem, taking a
      patient perspective. In particular, given a General Surgery Department made up of
      different surgical sub-specialties sharing a given number of OR block times, the
      model determines, during a given planning period, the allocation of those blocks
      to surgical sub-specialties, i.e. the so called Master Surgical Schedule Problem
      (MSSP), together with the subsets of elective patients to be operated on in each
      block time, i.e. the so called Surgical Case Assignment Problem (SCAP). The
      innovation of the model is two-fold. The first is that OR allocation is "optimal"
      if the available OR blocks are scheduled simultaneously to the proper
      subspecialty, at the proper time to the proper patient. The second is defining
      what "proper" means and include that in the objective function. In our approach
      what is important is not number of patients who can be treated in a given period
      but how much welfare loss, due to clinical deterioration or other negative
      consequences related to excessive waiting, can be prevented. In other words we
      assume a societal perspective in that we focus on "outcome" (health improving or
      preventing from worsening) rather than on "output" (delivered procedures). The
      model can be used both to develop weekly OR planning with given resources
      (operational decision), and to perform "what if" scenario analysis regarding how
      to increase the amount of OR time available for the entire department (tactical
      decision). The model performance is verified by applying it to a real scenario,
      the elective admissions of the General Surgery Department of the San Martino
      University Hospital in Genova (Italy). Despite the complexity of this NP-hard
      combinatorial optimization problem, computational results indicate that the model
      can solve all test problems within 600 s and an average optimality tolerance of
      less than 0.01%.

PMID- 20058527
TI  - What is a 'generic' hospital model?--a comparison of 'generic' and 'specific'
      hospital models of emergency patient flows.
AB  - The paper addresses the question in the title via a survey of experienced
      healthcare modellers and an extensive literature review. It has two objectives.
      1. To compare the characteristics of 'generic' and 'specific' models and their
      success in hospitals for emergency patients 2. To learn lessons about the design,
      validation and implementation of models of flows of emergency patients through
      acute hospitals First the survey and some key papers lead to a proposed 'spectrum
      of genericity', consisting of four levels. We focus on two of these levels,
      distinguished from each other by their purpose. Secondly modelling work on the
      flow of emergency patient flows through and between A&E, Bed Management, Surgery,
      Intensive Care and Diagnostics is then reviewed. Finally the review is used to
      provide a much more comprehensive comparison of'generic' and 'specific' models,
      distinguishing three types of genericity and identifying 24 important features of
      models and the associated modelling process. Many features are common across
      model types, but there are also important distinctions, with implications for
      model development.

PMID- 20058528
TI  - Reducing patient wait times and improving resource utilization at British
      Columbia Cancer Agency's ambulatory care unit through simulation.
AB  - We consider an ambulatory care unit (ACU) in a large cancer centre, where
      operational and resource utilization challenges led to overcrowding, excessive
      delays, and concerns regarding safety of critical patient care duties. We use
      simulation to analyze the simultaneous impact of operations, scheduling, and
      resource allocation on patient wait time, clinic overtime, and resource
      utilization. The impact of these factors has been studied before, but usually in
      isolation. Further, our model considers multiple clinics operating concurrently,
      and includes the extra burden of training residents and medical students during
      patient consults. Through scenario analyses we found that the best outcomes were
      obtained when not one but multiple changes were implemented simultaneously. We
      developed configurations that achieve a reduction of up to 70% in patient wait
      times and 25% in physical space requirements, with the same appointment volume.
      The key findings of the study are the importance of on time clinic start, the
      need for improved patient scheduling; and the potential improvements from
      allocating examination rooms flexibly and dynamically among individual clinics
      within each of the oncology programs. These findings are currently being
      evaluated for implementation by senior management.

PMID- 20058529
TI  - The performance of a generalized Bailey-Welch rule for outpatient appointment
      scheduling under inpatient and emergency demand.
AB  - We are considering the problem of scheduling a given number of outpatients to a
      medical service facility with two resources servicing outpatients, inpatients,
      and emergency patients. Each of the three patient classes has associated class
      specific arrival processes and cost-figures. The objective is to maximize the
      total expected reward which is made of revenues for served patients, costs for
      letting patients wait, and costs for denial of service. For this problem we
      propose a generalization of the well-known Bailey-Welch rule as well as a
      neighborhood search heuristic. We analyze the impact of different problem
      parameters on the total reward and the structure of the derived appointment
      schedules and address the question of the number of outpatients to be scheduled.
      The results show that the generalized Bailey-Welch rule performs astonishingly
      well over a wide range of problem parameters.

PMID- 20058530
TI  - How well does diagnosis-based risk-adjustment work for comparing ambulatory
      clinical outcomes?
AB  - This paper examines the empirical consistency of the Diagnosis Cost
      Groups/Hierarchical Condition Categories (DCG/HCC) risk-adjustment method for
      comparing 7-day mortality between hospital-based outpatient departments (HOPDs)
      and freestanding ambulatory surgery centers (ASCs). We used patient level data
      for the three most common outpatient procedures provided during the 1997-2004
      period in Florida. We estimated base-line logistic regression models without any
      diagnosis-based risk adjustment and compared them to logistic regression models
      with the DCG/HCC risk-adjustment, and to conditional logit models with a matched
      cohort risk-adjustment approach. We also evaluated models that adjusted for
      primary diagnoses only, and then for all available diagnoses, to assess how the
      frequently absent secondary diagnoses fields in ambulatory surgical data affect
      risk-adjustment. We found that risk-adjustment using both diagnosis-based methods
      resulted in similar 7-day mortality estimates for HOPD patients in comparison
      with ASC patients in two out of three procedures. We conclude that the DCG/HCC
      risk-adjustment method is relatively consistent and stable, and recommend this
      risk-adjustment method for health policy research and practice with ambulatory
      surgery data. We also recommend using risk-adjustment with all available
      diagnoses.

PMID- 20058531
TI  - Exploring information systems outsourcing in U.S. hospital-based health care
      delivery systems.
AB  - The purpose of this study is to explore the factors associated with outsourcing
      of information systems (IS) in hospital-based health care delivery systems, and
      to determine if there is a difference in IS outsourcing activity based on the
      strategic value of the outsourced functions. IS sourcing behavior is
      conceptualized as a case of vertical integration. A synthesis of strategic
      management theory (SMT) and transaction cost economics (TCE) serves as the
      theoretical framework. The sample consists of 1,365 hospital-based health care
      delivery systems that own 3,452 hospitals operating in 2004. The findings
      indicate that neither TCE nor SMT predicted outsourcing better than the other
      did. The findings also suggest that health care delivery system managers may not
      be considering significant factors when making sourcing decisions, including the
      relative strategic value of the functions they are outsourcing. It is consistent
      with previous literature to suggest that the high cost of IS may be the main
      factor driving the outsourcing decision.

PMID- 20058532
TI  - Adolescent medicine: state of the art reviews. Handbook of adolescent medicine.
      2nd edition.

PMID- 20058533
TI  - [Analysis of the active components of a complex intervention for the care
      management of stroke patients: impact on in-hospital mortality].
AB  - We conducted a cohort observational study in 29 Italian hospitals to identify
      which factors of the acute care management process of ischemic stroke patient can
      reduce in-hospital mortality. This complex intervention is based on some
      potential organizational and clinical active components, so data are collected
      both at organizational unit and individual patient level. We built the variables
      in relation to presence/absence of clinical-demographic, care-process and
      organizational characteristics. We compared categorical variables and evaluated
      the studied independent variables effects on the in-hospital mortality risk at 7
      and 30 days from admission. One of the main care success determinants is to be
      admitted in a stroke unit during the acute-stroke-phase. The most important
      organizational factor is to be short-time assessed by a stroke team: active role
      in patients' needs evaluation is provided by the stroke specialists'
      multidisciplinary team. Antithrombotic therapy is influencing mortality at 7 and
      30 days likewise: it is a indispensable factor for the clinical protocols. Our
      study emphasizes the fact that higher access to different and integrated levels
      of organized care is associated to better stroke outcomes and that some active
      and interactive components of the patient's care management have to be identified
      in the complex intervention.

PMID- 20058534
TI  - [Application of a pro-active method of risk analysis in communication among
      health personnel in an Italian medicine ward].
AB  - In the last decade health system stressed the question on patient's security as
      fundamental pre-requirement of health assistance and also on appropriateness and
      efficacy Aim of this study, conducted in the period November 2007-Genuary 2008,
      is the application of pro-active method (Health Failure Mode Effect Analysis -
      HFMEA) to analyze risks in communication among health personnel in a medicine
      ward of an Italian hospital. Communication is a error source: in some studies it
      was origin of 60% of adverse events that occurred in hospital accredited at
      excellence. HFMEA method permitted, throughout the work of a multidisciplinary
      team, a systematic approach to critical processes to decompose them and to
      recognize probability of occurrence and injure importance, permitting to define a
      Priority Index of Risk (RPI) with formula risk=probability of occurrence x injure
      severity. In the study results error modality at high risk were those regards to
      development of following activities: assistance activities without supervision of
      nurse, post meridiem activities in which admissions/recharges are concentrated in
      a short time, collection of informative consensus to haemo-transfusion, nocturne
      assistance. Middle risk processes were resulted: urgent admission, examination
      round, graphic manage. In conclusion with application of HFMEA, without needs of
      additional resources, critical points that determined frequently errors were
      defined throughout a positive and pro-active approach regards to health
      personnel. The method stress attention to knowledge of phenomenon and to analysis
      of error modality to permit the prevention.

PMID- 20058535
TI  - [Assessment and monitoring of organizational appropriateness of inpatient
      rehabilitation facilities in Lazio region: tools and working methods, results and
      comparison with other regional experiences].
AB  - Aim of this paper is to analyze the tools and working methods, used in the Lazio
      Region, to assess organizational appropriateness in the context of Inpatient
      Rehabilitation Facilities, and the results obtained. It illustrates also the
      regional experiences of Veneto and Lombardia, which characterized by dynamism and
      originality in an attempt to overcome the obvious place for the critical
      assessment of this area of care.

PMID- 20058536
TI  - [The plan for prevention of obesity of ASL RMB, Italy].
AB  - Lazio District, by pointing out the guidelines of the "Obesity and Overweight for
      Lazio District Plan" (DGR no1166, 23/12/05), enacts the "National Prevention Plan
      2005-2007". The Public Health Service for Food and Nutrition has been the main
      player of the Plan; the District and Department of Health of the District had a
      technical and organizational support role. Within the development of the Plan for
      prevention of obesity of ASL RMB, a technical multidisciplinary group was
      constituted and three more programs were developed, all of them were dedicated to
      promotion and support of breast-feeding, prevention of obesity and overweight in
      childhood and adulthood. The educational activity concerning promotion and
      support of breast-feed ing actively involved operators from consultory rooms and
      hospital staff from ASL. The reports about nutritional surveillance allowed a
      careful analysis of the service conditions and priorities. Special criticality
      facets have been pointed out such as the high prevalence of overweight (31%) and
      obesity (7%), the habit of skipping breakfast, a low fruit and vegetables
      consumption, a generally sedentary lifestyle and, during the intervention, the
      parents' low involvement. In geriatric age cases, a high malnutrition risk both
      for overnutrition and undernutrition was found in the elderly groups that were
      checked; the diets' nutritional density as well as the physical activity aspect
      recover an important role in the intervention planning. Moreover the discussions
      with catering companies were an important aspect in order to make several target
      groups aware. The globally considered experience highlighted positive elements of
      mobilization, consensus, reorientation of activities and resources, giving proof
      of the significance of integration concerning specifical aims of different
      company services. Nevertheless, the carrying on of such activities needs resource
      investments in the specifical area and enlargement of activities especially for
      the multisector-based efforts.

PMID- 20058537
TI  - [A method to estimate one's own blood alcohol concentration when the ministerial
      tables are not avaible].
AB  - To reduce the prevalence of driving under the influence, tables allowing to
      estimate one's own blood alcohol concentration (BAC) by type and quantity of
      alcoholic drinks intake have been enacted by decree in Italy. Such tables, based
      on a modified Widmark's formula, are now put up in all public concerns serving
      alcoholic beverages. Aim of this initiative is to try to get subjects which
      consume alcoholics and then will drive a vehicle take in account their own
      estimated BAC and, on this base, put into effect, if needed, suitable actions (to
      avoid or to limit a further consumption, to wait more time before driving, to
      leave driving a sober subject). Nevertheless, many occasions exist in which these
      tables are not available. To allow anybody to rough estimate his own BAC in these
      cases too, a proper method has been developed. Briefly, the weight (in grams) of
      consumed alcohol has to be divided by half her own weight, if female drunk on an
      empty stomach (by the 90% of her own weight, if she drunk on a full stomach); by
      70% of his own weight, if male drunk on an empty stomach (by 120% of his own
      weight, if he drunk in a full stomach). Consistency between BAC values estimated
      by the proposed method and those shown in the ministerial tables is very narrow:
      they differ in a few hundredth of grams/liter. Unlike the ministerial tables, the
      proposed method needs to compute the grams of ingested alcohol. This maybe
      involves some difficulties that, nevertheless, can be overcome easily. In our
      opinion, the skillfulness in computing the grams of assumed alcohol is of great
      significance since it provides the subject with a strong signal not only in road
      safety terms, but also in health terms. The ministerial tables and the proposed
      method should be part of teaching to issue the driving licence and to recovery of
      driving licence taken away points. In broad terms, the school should teach youngs
      to calculate alcohol quantities assumed by drink to acquaint them with the risks
      paving the way for a more aware drinking when they will come age.

PMID- 20058538
TI  - [Evolution of hospital concept in Italy].
AB  - Hospital building trade was born before the origin of Healthcare System and
      followed the complex development of healthcare during all the past years to
      present day. At the beginning of 700's, when infective pathology was predominant
      and hygienic conditions was parameter of quality, pavilions structure took place.
      These hospitals required wide land to be built on, with a high surface area to
      volume ratio and a horizontal development. There were about 1200-1500 sleeping
      accommodations in large rooms (ward) where patients were split up. The typical
      pavilions structure were used until half 900's when it was replaced with a new
      concept of building trade, the mono-polibloc. They were buildings with vertical
      development that minimized horizontal distances and operating costs. Every floor
      has confinement and service rooms and represent a single and autonomous operating
      unit. Nowadays hospitals building trade point to use the flat-tower model that
      enhance the distinction between confinement area (with a vertical development
      monobloc) and diagnosis, care and services area (with a horizontal development
      flat). The challenge we willface in the future is to convert healthcare buildings
      to other uses like trading centres and services areas, to improve structures'
      flexibility, to better include them in the context of the urban and natural
      setting.

PMID- 20058539
TI  - [Mass screening and early detection of cancer: organizational characteristics of
      preventive services in Italy].
AB  - The commitment to fight against cancer is a part of European Community health
      strategies and of Italian health services planning. Interesting and useful
      results have been achieved in Europe and in our country where most of the
      population can participate to screening programmes. In Italy there are two main
      organisational models to deliver intervention for secondary prevention:
      population based and individual access. Several experimental data show population
      based prevention is more fair and appropriate and achieves better results in
      reducing incidence and mortality rates; data are summarized. Because of this
      differences we go trough the different characteristics of the two models to
      handle them better planning and managing more efficiently a sustainable secondary
      prevention.

PMID- 20058540
TI  - [Health evaluation of the population of the city of Trino Vercellese:
      epidemiological study on cancer incidence and mortality].
AB  - The study includes an analysis of the state of health of the inhabitants of the
      City of Trino, County of Vercelli, 15 km south-west of the capital town. With
      industries making a significant environmental impact and an old nuclear centre
      under dismantlement, in recent years, the City has often been mentioned in local
      newspapers and pressurised by residents and local associations. Hence the drawing
      up of this study to describe the state of health of residents and cancer
      pathologies (incidence and mortality rate) and, consequently, to evaluate the
      need for further epidemiological analysis. The rates (SIR and SMR) were obtained
      by calculating the expected results compared with those of the Local Health
      Authority of Vercelli and the Airtum registries of Northern Italy: the results
      (divided by sex) highlight significant excesses in neoplasias of the mouth,
      nervous system, peritoneum in addition to eukaemias and mesoteliomas.
      Furthermore, the analysis by age shows epidemiological anomalies both at
      paediatric (0-14 years) and young people (0-44 years) levels: these results
      certainly require further epidemiological research through aetiological studies,
      including an ad hoc questionnaire.

PMID- 20058541
TI  - [Rad-Esito: new informational debt as integration of hospital discharge cards for
      acute patients].
AB  - Since the January 2008 the tracking of additional information about hospital
      discharge card's content has been activated in Latium. The new data, noticed by
      RAD-Esito card, regard the hospitalizations for acute myocardial infarction,
      femoral neck fracture and coronary artery bypass surgery. This study's objective
      has been to evaluate the quality of the data collected with the new card, at the
      end of the 1st semester of experimentation, concerning two institutes of care of
      Latium (Region of Central Italy), the Casilino Polyclinic (ASL Rome B) and the
      Anzio-Nettuno hospital (Assembled Hospitals, ASL Rome H). Furthermore, any
      significant correlation's existence between variables for acute myocardial
      infarction and femoral fracture with the mortality rate and an increased average
      hospitalization period has been statistically verified. In acute myocardial
      infarction mortality is significantly related to a low systolic blood pressure
      (<130 mmHg) at admission (p < 0.02) and to having no surgical intervention
      instead of transcutaneous transluminal coronary angioplastic surgery (p <
      0.0001); in this case there is also an increased average hospitalization period
      (p < 0.03). In femoral neck fracture mortality is significantly related to having
      a conservative surgery instead of fracture reduction or prosthesis implantation
      (p < 0.0002).This study's preliminary results show how the integration of the
      hospital informative flow with the new clinical variables will be able to allow
      the promotion of the quality in the coding of the diagnosis and procedures,
      according to the current international innovations. This additional information
      will also be able to support the regional appropriateness and outcome of the
      treatments evaluation programs.

PMID- 20058542
TI  - [Investigation on strains of Legionella pneumophila, isolated from a hospital of
      Milano, with three genotyping methods].
AB  - Various techniques have been developed in recent years for the molecular typing
      of microorganisms. Remains particularly difficult to isolate clinical strains for
      the low availability of cases and even more problematic matching clinical /
      environmental strains. We investigated 13 strains of Legionella pneumophila of
      clinical and environmental origin, isolated in 3 Health Facilities in Milan (2003
      2006), using three molecular typing methods: Pulse-Field Gel Electrophoresis,
      Amplified Fragment Length Polymorphism and Sequence-Based Typing. PFGE and AFLP
      showed the correlation between a clinical case with only one of the environmental
      isolates taken from the places frequented by the patient, demonstrating with
      certainty the nosocomial origin of the case and identifying the source of
      infection in the shower water (Clin. 1 and Env. 1N). Two clinical samples from
      patients admitted to different wards presented an identical profile, which
      suggests that the nosocomial origin assumed an epidemic form, even without having
      isolated the environmental strain due to the absence of samples drawn during the
      period under consideration (Clin. 2 and 3). Finally, the comparison between the
      isolated environmental strains demonstrated a heterogeneous presence of strains,
      not correlated to each other although they belong to the same serum-group, having
      profiles that are clearly different regarding number and position of bands (Env.
      2 and 4). The profile 2,10,18,10,1,1 had never been isolated and typed previously
      in Europe. The SBT has proved a better technique for reproducibility and
      interpretation of results than PFGE and AFLP To complete studies on SBT method,
      now considered gold standard, is currently being the EWGLI 5th Proficiency Panel,
      in which we are actively involved with the genotyping of five strains according
      to the latest version of the protocol (4.1).

PMID- 20058543
TI  - A transient VEP-based real-time brain-computer interface using non-direct gazed
      visual stimuli.
AB  - It is necessary for brain-computer interfaces (BCIs) to be non-offensive devices
      for daily use to improve the quality of life of users, especially for the motor
      disabled. Some BCIs which are based on steady-state visual evoked potentials
      (SSVEPs), however, are unpleasant because users have to gaze at high-speed
      blinking light as visual stimuli. Furthermore, these kinds of BCIs may not be
      used as universal devices because SSVEPs are not detectable by some users.
      Considering these facts, we previously proposed a BCI using a non-direct gazing
      method based on transient VEPs. This interface used a low-speed blinking lattice
      pattern as visual stimuli and visual targets displayed on the right and the left
      sides of the stimuli. The gazing direction was determined by the waveform
      difference of transient VEPs detected when users gazed at either target. Compared
      with SSVEP-based BCLs, this BCI was less annoying because it used low-speed
      blinking visual stimuli, and it was not necessary for users to gaze at the
      stimuli directly. In this study, we propose an improved version of the BCI.
      Specifically, the gazing direction is determined in real time, and another gazing
      direction in which users gaze at a visual target displayed on the center of the
      screen is introduced while maintaining the annoyance-free advantage of the BCI.
      Experiments with 6 volunteer subjects showed an 84.2% accuracy rate in gazing
      direction judgments. The result suggests that the proposed BCI is more practical
      than the previous one because it can adapt to the change of gazing direction in
      real time.

PMID- 20058544
TI  - Coordination impairment between the somatic and parasympathetic nervous system
      divisions in the human sacral micturition centre following spinal cord injury.
AB  - The detrusor-sphincteric dyssynergia is analyzed by comparing the natural impulse
      patterns of secondary muscle spindle afferents (SP2) contributing to continence
      (SP2 fibre activity changes are similar to detrusor pressure changes) and
      sphincteric motoneurons in a brain-dead human with those in patients with spinal
      cord injuries. In the brain-dead the sphincteric motoneurons, subserving
      continence, were inhibited at a time, when preganglionic parasympathetic
      efferents and a SP2 fibre increased their activity (physiologic). In paraplegics
      the sphincteric motoneurons were not inhibited (pathophysiologic). In the brain
      dead, an SP2 fibre showed doublet firing (interspike interval (II) 10 to 14 ms)
      for low level parasympathetic activation and multi-ending regular firing for high
      parasympathetic activation. In one paraplegic with strong bladder dysfunction,
      the multi-ending regular firing was replaced by a repeated burst firing with a
      shortest II of 0.2 ms (transmission frequency = 5000 Hz). The pathologic firing
      patterns of the SP2 fibres, the detrusor-sphincteric dyscoordination, and
      hyperreflexia in paraplegics are most likely a result of neuronal network changes
      in the parasympathetic and somatic nervous system divisions of the sacral
      micturition center after spinal cord injury. It is discussed that urinary bladder
      functions can be re-learned.

PMID- 20058545
TI  - Autologous blood injection in carpal tunnel syndrome (CTS).
AB  - INTRODUCTION: Most medical treatments for carpal tunnel syndrome (CTS) have
      focused on suppressing the inflammatory process. An injection of autologous blood
      might provide the necessary cellular and humoral mediators to induce a healing
      cascade. The purpose of this study was to evaluate prospectively autologous blood
      injection in CTS. METHOD & MATERIALS: Twenty patients with CTS were recruited
      using strict inclusion and exclusion criterias. All patients were injected with 1
      ml of autologous blood and 0.5 ml lidocaeine 1% under the carpal tunnel. Pain
      intensity (based on VAS) and electrophysiologic parameters of median nerve
      (transcarpal SNCV, DML and DSL) were recorded before and 3 weeks after autologous
      blood injection. RESULTS: The average pain scores before and 3 weeks after
      autologous blood injection was 8.70 +/- 0.92 and 4.30 +/- 0.76 respectively (P <
      0.005). Also transcarpal SNCV of median nerve was 33.7 +/- 6.3 m/s and 24.5 +/-
      6.8 m/s (P = 0.001); DML of medin nerve was 5.16 +/- 1.04 ms and 4.70 +/- 0.53 ms
      (P = 0.001) and DSL of median nerve was 4.84 +/- 0.77 ms and 4.2 +/- 0.6 ms (P =
      0.001), respectively. CONCLUSIONS: After autologous blood injection, pain
      intensity and electerophysiologic parameters were significantly improved. This
      study offers encouraging results for an alternative minimally invasive treatment
      for CTS. This study cannot prove conclusively whether the blood itself induced an
      inflammatory cascade or the injury created by the injection was responsible.

PMID- 20058546
TI  - Clinical and EMG findings in patient with mononeuropathy multiplex associated
      with livedo reticularis: a case report.
AB  - We report on the combination of biopsy-proven idiopathic livedo reticularis and
      mononeuropathy multiplex, mild to moderate in severity and remitting-relapsing in
      course, observed in a young otherwise healthy woman. Neurologic relapses were
      always accompanied or preceded by exacerbation of the skin lesion. After 18 years
      followup we did not detect clinical or instrumental evidence of brain or visceral
      involvement. This excludes the classical Sneddon's syndrome and points at an
      unusual variant of this syndrome in our patient.

PMID- 20058547
TI  - Lumbo-pelvic stability and electromyography of abdominal muscles in ballet
      dancers.
AB  - Evaluating the ability to rectify and maintain lumbar adjustment can contribute
      toward the understanding of the behavior of abdominal muscles and their
      participation in the stability of pelvic muscles in dancers during the posterior
      pelvic tilt and double straight leg lowering tests. Nine healthy volunteers (male
      and female ballet dancers; age mean: 25.9 +/- 7.37 years) underwent maximal
      isometric voluntary contraction (MIVC), isometric voluntary contraction at 50% of
      MIVC, posterior pelvic tilt (PPT) and double straight leg lowering (DSLL) tests.
      The tests were carried out in a single day, with 3 repetitions each. During the
      tests, electromygraphic signals of the rectus abdominis, obliquus internus and
      obliquus externus were recorded. The signal acquisition system was made up of
      bipolar surface electrodes, electrogoniometer and an electromechanic device
      (pressure sensor), which were connected to a signal conditioner module. Root mean
      square values of each muscle during the DSLL and PPT were converted into
      percentage of activation of 50% MIVC. Lower back pressure was submitted to the
      same process. ANOVA with repeated measures was performed, with the level of
      significance set at p < 0.05. The results revealed that all dancers were able to
      maintain posterior pelvic tilt and there was trend toward greater activation of
      the bilateral obliquus internus muscle. In an attempt to keep the pelvic region
      stabilized during DSLL, there was a greater contribution from the obliquus
      externus muscle in relation to other abdominal muscles.

PMID- 20058548
TI  - Prognosticative Extensions and Enhancements to Existing Practices: a
      Biomechanical PEEEP Show into the Future.
AB  - With the rapidly expanding capabilities and sophistication of experimental and
      analytical techniques that can be applied toward biomechanical endeavors, it
      would appear to be a useful exercise to review current practice and discuss what
      might be the form and function of future research that could make substantial
      improvements in the ability to detect and evaluate the potential for automotive
      impact trauma. To accomplish this, an exercise, dubbed Prognosticative Extensions
      and Enhancements to Existing Practices: a Biomechanical PEEEP Show into the
      Future, will be pursued and presented. It presents the author's impressions of
      what are the prevalent injury mechanisms active in each major body region, his
      technical evaluation of the efficacy of the currently accepted injury criteria
      being applied to detect and evaluate the consequences of those injury mechanisms,
      and presents his vision of the form and function of future biomechanical
      capabilities that could, using both enhanced analytical and experimental research
      techniques, have the potential for greatly improving both our understanding of
      impact injuries and our ability to prevent them.

PMID- 20058549
TI  - Impact response of restrained PMHS in frontal sled tests: skeletal deformation
      patterns under seat belt loading.
AB  - This study evaluated the response of restrained post-mortem human subjects (PMHS)
      in 40 km/h frontal sled tests. Eight male PMHS were restrained on a rigid planar
      seat by a custom 3-point shoulder and lap belt. A video motion tracking system
      measured three-dimensional trajectories of multiple skeletal sites on the torso
      allowing quantification of ribcage deformation. Anterior and superior
      displacement of the lower ribcage may have contributed to sternal fractures
      occurring early in the event, at displacement levels below those typically
      considered injurious, suggesting that fracture risk is not fully described by
      traditional definitions of chest deformation. The methodology presented here
      produced novel kinematic data that will be useful in developing biofidelic human
      models. Additional analysis of the data produced by the reported tests as well as
      additional tests with a variety of loading conditions are required to fully
      characterize torso response including ribcage fracture tolerance.

PMID- 20058550
TI  - Rear seat occupant safety: an investigation of a progressive force-limiting,
      pretensioning 3-point belt system using adult PMHS in frontal sled tests.
AB  - Rear seat adult occupant protection is receiving increased attention from the
      automotive safety community. Recent anthropomorphic test device (ATD) studies
      have suggested that it may be possible to improve kinematics and reduce injuries
      to rear seat occupants in frontal collisions by incorporating shoulder-belt force
      limiting and pretensioning (FL+PT) technologies into rear seat 3-point belt
      restraints. This study seeks to further investigate the feasibility and potential
      kinematic benefits of a FL+PT rear seat, 3-point belt restraint system in a
      series of 48 kmh frontal impact sled tests (20 g, 80 ms sled acceleration pulse)
      performed with post mortem human surrogates (PMHS). Three PMHS were tested with a
      3-point belt restraint with a progressive (two-stage) force limiting and
      pretensioing retractor in a sled buck representing the rear seat occupant
      environment of a 2004 mid-sized sedan. Instrumentation included belt tension load
      cells, accelerometers on the head and at multiple locations on the spine, and
      chestbands to measure the chest deformation contours in the transverse plane. The
      kinematics of the subjects were quantified using off-board, high-speed video. The
      results of these tests were then compared to matched PMHS tests, published in
      2008, performed in the same environment with a standard (not-force limited, not
      pretensioning) 3-point belt restraint. The FL+PT restraint system resulted in
      significant (p<0.05) decreases in peak shoulder belt tension (average +/-
      standard deviation: 4.4 +/- 0.13 kN with the FL+PT belt, 7.8 +/- 0. 6 kN with the
      standard belt) and 3 ms-resultant, mid-spine acceleration (FL+PT: 34 +/- 3.8 g;
      standard belt: 44 +/- 1.4 g). The FL+PT tests also produced more forward torso
      rotation caused by decreased forward excursion of the pelvis and increased payout
      out of the shoulder belt by the force-limiter. These results support the previous
      ATD studies that suggest that it may be possible to improve the kinematics of
      rear seat occupants in this type of collision using a 3-point belt system with a
      shoulder belt retractor equipped with a two-stage force-limiter and pretensioner.

PMID- 20058551
TI  - Protection of rear seat occupants in frontal crashes, controlling for occupant
      and crash characteristics.
AB  - In this study, the level of protection offered to rear seat occupants in frontal
      crashes is investigated. The Fatality Analysis Reporting System (FARS) and
      National Automotive Sampling System Crashworthiness Data System (NASS CDS)
      databases were used for the analyses. The investigation focused on: 1- estimating
      the fatality protection effectiveness of the rear seat position relative to the
      right front seat position, using the double paired comparison method, 2-
      evaluating the effect of control group selection method on effectiveness
      predictions, and 3- identifying trends in rear seat occupant protection over
      model years of vehicles. By applying a uniform control group to the double paired
      comparison analysis of FARS data, this study suggests that all ages of occupants
      are safer in the rear seat than in the right front seat. Effectiveness estimates
      ranged from 5.9% to 82% for different age groups of occupants. Results indicate
      that although occupants overall benefit from sitting in the rear seat compared to
      the right front seat, for all model year vehicles, the protective effect of the
      rear seat relative to that of the right front seat has decreased in the newer
      model year vehicles. The reduction in the effectiveness was 43.7% for unbelted
      occupants and 33.5% for belted occupants. Logistic regression analysis on NASS
      CDS data shows that vehicle model year has a significant effect (p-value =
      0.0043) on increasing the risk of injury for belted rear seat occupants.
      Considering these results, protection of rear seat occupants deserves more
      attention from the automotive industry and government agencies.

PMID- 20058552
TI  - Structural characterization of human rib cage behavior under dynamic loading.
AB  - Tests were conducted on four rib cages to characterize their 3D deformation and
      the kinematics of the costovertebral joints. The influence of the structural
      properties, i.e. geometry and initial rib slopes, and of the costo-vertebral
      joints on the deformation capacity of the rib cage during a dynamic loading was
      studied. Each rib cage was loaded four times by increasing, up to 40% of the
      initial thickness, the mid-sternum deflection. The spine was rigidly fixed
      without constraining the costo-vertebral joints and the rib motions were computed
      from 3D video analysis. In addition, numerical simulations were performed with
      subject-specific models obtained from the rib cage geometry and a method for
      model personalization. The objective was to numerically evaluate the sensitivity
      to solely changes in geometry. The rib rotations were determined from the motion
      of 3D-markers close to the costo-vertebral joints and the 3D rib deformations
      were assessed from the motion of markers along the ribs. The rib rotations varied
      with the costal level (mean value 5.8 degrees [max. 7.9 degrees, min. 3.5
      degrees], 2.9 degrees [4.8 degrees, 1.0 degree], 2.5 degrees [4.8 degrees, 1.1
      degrees] and 2.2 degrees [3.5 degrees, 0.8 degree] for rib 2, 4, 6 and 8
      respectively) and among the subjects (mean variation from 3.3 degrees to 7.1
      degrees). The rib deformations were mainly in the sagittal plane for the upper
      ribs and in the rib plane for the lower. Although, no statistically significant
      correlations were found with different morphometrics parameters, a link (R2>0.4)
      was found between the initial rib slope and the amount of rotation and
      deformations, according to the assumption described by Kent et al (2005). The
      costovertebral joint was described by a functional rotation axis (i.e. helical
      axis) that does not correspond to the physiological axis of rotation. The
      orientation and the position of this helical axis changed with the level of
      deflection and varied with the costal level.

PMID- 20058553
TI  - The effects of posture and subject-to-subject variations on the position, shape
      and volume of abdominal and thoracic organs.
AB  - In this study, the thorax and the abdomen of nine subjects were imaged in four
      postures using a positional MRI scanner. The four postures were seated, standing,
      forward-flexed and supine. They were selected to represent car occupants,
      pedestrians, cyclists and a typical position for medical imaging, respectively.
      Geometrical models of key anatomical structures were registered from the imaging
      dataset using a custom registration toolbox. The analysis of the images and
      models allowed the quantification of the respective effects of posture and
      subject-to-subject variation on the position, shape and volume of the abdominal
      organs, skeletal components and thoracic cavity. In summary, except for the
      supine posture, the organ volumes and their positions in the spinal frame were
      mostly unaffected by the posture. The supine posture was associated with a motion
      of all solid organs of up to 39 mm (interpostural maximum for the liver, n=9),
      and a reduction of the thoracic cavity volume of up to 1300 cm3. Subject-to
      subject variations were especially large for the volume of the spleen (variations
      between 120 and 400 cm3) and the position of the kidneys. As a result, subject-to
      subject variations were larger than most postural effects. Other results include
      values of parameters that can help positioning human models such as positions,
      volumes and inertial properties of organs as well as skeletal parameters.
      Overall, this study suggests that subject-to-subject variations and the use of
      supine geometrical data can be problematic for finite element modeling of the
      abdomen for injury prediction.

PMID- 20058554
TI  - Evaluation of thoracic deflection as an injury criterion for side impact using a
      finite elements thorax model.
AB  - This study aims to investigate the relationship between the number of rib
      fractures and the thoracic deflection in side impact, and in particular its
      variability with respect to various loading configurations. The relevance of
      thoracic deflection as an injury criterion depends on the existence or not of
      this variability. Few studies were dedicated to this issue in the literature.
      First, a validation database was established, which covers different impact
      directions (frontal, lateral and oblique), different loading types (impactor,
      belt and airbag), and different injury levels (from the absence of, to presence
      of numerous ribs fractured). The HUMOS human body model was then modified and
      validated versus the database. Besides the typical validation in terms of global
      response, particular attention was paid to validate the model with respect to the
      ribcage strain profile, the occurrence of rib fractures and their locations. Some
      key features relative to the thorax modeling (such as the connection between the
      ribcage and the surrounding tissues) were also investigated. Using this model,
      the relationship between the rib fracture and thoracic deflection was studied
      versus loading type. It was demonstrated that this relationship does not change
      significantly from one loading type to another, supporting the thoracic
      deflection as a relevant indicator of ribcage injury level. In addition, the
      relationship between the thoracic response and the test severity (such as impact
      velocity or distance between airbag and subject), was also established for each
      kind of loading. These relationships, obtained over a unique subject, are free of
      uncertainty relative to cadaver scattering, measurement and autopsy. They provide
      a consistent characterization of thoracic injuries under various test conditions
      and therefore, can be used to guide cadaver test protocol development and result
      analysis.

PMID- 20058555
TI  - A finite element model of region-specific response for mild diffuse brain injury.
AB  - It is well known that rotational loading is responsible for a spectrum of diffuse
      brain injuries spanning from concussion to diffuse axonal trauma. Many
      experimental studies have been performed to understand the pathological and
      biomechanical factors associated with diffuse brain injuries. Finite element
      models have also been developed to correlate experimental findings with intrinsic
      variables such as strain. However, a paucity of studies exist examining the
      combined role of the strain-time parameter. Consequently, using the principles of
      finite element analysis, the present study introduced the concept of sustained
      maximum principal strain (SMPS) criterion and explored its potential
      applicability to diffuse brain injury. An algorithm was developed to determine if
      the principal strain in a finite element of the brain exceeded a specified
      magnitude over a specific time interval. The anatomical and geometrical details
      of the rat for the two-dimensional model were obtained from published data. Using
      material properties from literature and iterative techniques, the model was
      validated under three distinct rotational loading conditions indicative of non
      injury, concussion, and diffuse axonal trauma. Validation results produced a set
      of material properties to define the model and were deemed appropriate to examine
      the role of sustained strain as an indicator of the mechanics of mild diffuse
      brain injury at the local level. Using a separate set of histological data
      obtained from graded mild diffuse brain injury experimental studies in rats,
      different formulations of SMPS criterion were evaluated. For the hippocampus and
      parietal cortex regions, 4-4 SMPS criterion was found to most closely match with
      the pattern of histological results. This was further verified by correlating the
      fractional areas to the time of unconsciousness for each animal group. Although
      not fully conclusive, these results are valuable in the understanding of diffuse
      brain injury pathologies following rotational loading.

PMID- 20058556
TI  - Experimental study of blast-induced traumatic brain injury using a physical head
      model.
AB  - This study was conducted to quantify intracranial biomechanical responses and
      external blast overpressures using physical head model to understand the
      biomechanics of blast traumatic brain injury and to provide experimental data for
      computer simulation of blast-induced brain trauma. Ellipsoidal-shaped physical
      head models, made from 3-mm polycarbonate shell filled with Sylgard 527 silicon
      gel, were used. Six blast tests were conducted in frontal, side, and 45 degrees
      oblique orientations. External blast overpressures and internal pressures were
      quantified with ballistic pressure sensors. Blast overpressures, ranging from
      129.5 kPa to 769.3 kPa, were generated using a rigid cannon and 1.3 to 3.0 grams
      of pentaerythritol tetranitrate (PETN) plastic sheet explosive (explosive yield
      of 13.24 kJ and TNT equivalent mass of 2.87 grams for 3 grams of material). The
      PETN plastic sheet explosive consisted of 63% PETN powder, 29% plasticizer, and
      8% nitrocellulose with a density of 1.48 g/cm3 and detonation velocity of 6.8
      km/s. Propagation and reflection of the shockwave was captured using a
      shadowgraph technique. Shockwave speeds ranging from 423.3 m/s to 680.3 m/s were
      recorded. The model demonstrated a two-stage response: a pressure dominant
      (overpressure) stage followed by kinematic dominant (blast wind) stage. Positive
      pressures in the brain simulant ranged from 75.1 kPa to 1095 kPa, and negative
      pressures ranged from -43.6 kPa to -646.0 kPa. High- and normal-speed videos did
      not reveal observable deformations in the brain simulant from the neutral density
      markers embedded in the midsagittal plane of the head model. Amplitudes of the
      internal positive and negative pressures were found to linearly correlate with
      external overpressure. Results from the current study suggested a pressure
      dominant brain injury mechanism instead of strain injury mechanism under the
      blast severity of the current study. These quantitative results also served as
      the validation and calibration data for computer simulation models of blast brain
      injuries.

PMID- 20058557
TI  - Lower extremity injury criteria for evaluating military vehicle occupant injury
      in underbelly blast events.
AB  - Anti-vehicular (AV) landmines and improvised explosive devices (IED) have
      accounted for more than half of the United States military hostile casualties and
      wounded in Operation Iraqi Freedom (OIF) (Department of Defense Personnel &
      Procurement Statistics, 2009). The lower extremity is the predominantly injured
      body region following an AV mine or IED blast accounting for 26 percent of all
      combat injuries in OIF (Owens et al., 2007). Detonations occurring under the
      vehicle transmit high amplitude and short duration axial loads onto the foot
      ankle-tibia region of the occupant causing injuries to the lower leg. The current
      effort was initiated to develop lower extremity injury criteria for occupants
      involved in underbelly blast impacts. Eighteen lower extremity post mortem human
      specimens (PMHS) were instrumented with an implantable load cell and strain gages
      and impacted at one of three incrementally severe AV axial loading conditions.
      Twelve of the 18 PMHS specimens sustained fractures of the calcaneus, talus,
      fibula and/or tibia. The initiation of skeletal injury was precisely detected by
      strain gages and corresponded with local peak axial tibia force. Survival
      analysis identified peak axial tibia force and impactor velocity as the two best
      predictors of incapacitating injury. A tibia axial force of 5,931 N and impactor
      velocity of 10.8 m/s corresponds with a 50 percent risk of an incapacitating
      injury. The criteria may be utilized to predict the probability of lower
      extremity incapacitating injury in underbelly blast impacts.

PMID- 20058558
TI  - The tolerance of the femoral shaft in combined axial compression and bending
      loading.
AB  - The likelihood of a front seat occupant sustaining a femoral shaft fracture in a
      frontal crash has traditionally been assessed by an injury criterion relying
      solely on the axial force in the femur. However, recently published analyses of
      real world data indicate that femoral shaft fracture occurs at axial loads levels
      below those found experimentally. One hypothesis attempting to explain this
      discrepancy suggests that femoral shaft fracture tends to occur as a result of
      combined axial compression and applied bending. The current study aims to
      evaluate this hypothesis by investigating how these two loading components
      interact. Femoral shafts harvested from human cadavers were loaded to failure in
      axial compression, sagittal plane bending, and combined axial compression and
      sagittal plane bending. All specimens subjected to bending and combined loading
      fractured midshaft, whereas the specimens loaded in axial compression
      demonstrated a variety of failure locations including midshaft and distal end.
      The interaction between the recorded levels of applied moment and axial
      compression force at fracture were evaluated using two different analysis
      methods: fitting of an analytical model to the experimental data and multiple
      regression analysis. The two analysis methods yielded very similar relationships
      between applied moment and axial compression force at midshaft fracture. The
      results indicate that posteroanterior bending reduces the tolerance of the
      femoral shaft to axial compression and that that this type of combined loading
      therefore may contribute to the high prevalence of femoral shaft fracture in
      frontal crashes.

PMID- 20058559
TI  - Predicting the effects of muscle activation on knee, thigh, and hip injuries in
      frontal crashes using a finite-element model with muscle forces from subject
      testing and musculoskeletal modeling.
AB  - In a previous study, the authors reported on the development of a finite-element
      model of the midsize male pelvis and lower extremities with lower-extremity
      musculature that was validated using PMHS knee-impact response data. Knee-impact
      simulations with this model were performed using forces from four muscles in the
      lower extremities associated with two-foot bracing reported in the literature to
      provide preliminary estimates of the effects of lower-extremity muscle activation
      on knee-thigh-hip injury potential in frontal impacts. The current study
      addresses a major limitation of these preliminary simulations by using the
      AnyBody three-dimensional musculoskeletal model to estimate muscle forces
      produced in 35 muscles in each lower extremity during emergency one-foot braking.
      To check the predictions of the AnyBody Model, activation levels of twelve major
      muscles in the hip and lower extremities were measured using surface EMG
      electrodes on 12 midsize-male subjects performing simulated maximum and 50% of
      maximum braking in a laboratory seating buck. Comparisons between test results
      and the predictions of the AnyBody Model when it was used to simulate these same
      braking tests suggest that the AnyBody model appropriately predicts agonistic
      muscle activations but under predicts antagonistic muscle activations.
      Simulations of knee-to-knee-bolster impacts were performed by impacting the knees
      of the lower-extremity finite element model with and without the muscle forces
      predicted by the validated AnyBody Model. Results of these simulations confirm
      previous findings that muscle tension increases knee-impact force by increasing
      the effective mass of the KTH complex due to tighter coupling of muscle mass to
      bone. They also indicate that muscle activation preferentially couples mass
      distal to the hip, thereby accentuating the decrease in femur force from the knee
      to the hip. However, the reduction in force transmitted from the knee to the hip
      is offset by the increased force at the knee and by increased compressive forces
      at the hip due to activation of lower-extremity muscles. As a result,
      approximately 45% to 60% and 50% to 65% of the force applied to the knee is
      applied to the hip in the simulations without and with muscle tension,
      respectively. The simulation results suggest that lower-extremity muscle tension
      has little effect on the risk of hip injuries, but it increases the bending
      moments in the femoral shaft, thereby increasing the risk of femoral shaft
      fractures by 20%-40%. However, these findings may be affected by the inability of
      the AnyBody Model to appropriately predict antagonistic muscle forces.

PMID- 20058560
TI  - Comparison of kinematic responses of the head and spine for children and adults
      in low-speed frontal sled tests.
AB  - Previous research has suggested that the pediatric ATD spine, developed from
      scaling the adult ATD spine, may not adequately represent a child's spine and
      thus may lead to important differences in the ATD head trajectory relative to a
      human. To gain further insight into this issue, the objectives of this study
      were, through non-injurious frontal sled tests on human volunteers, to 1)
      quantify the kinematic responses of the restrained child's head and spine and 2)
      compare pediatric kinematic responses to those of the adult. Low-speed frontal
      sled tests were conducted using male human volunteers (20 subjects: 6-14 years
      old, 10 subjects: 18-40 years old), in which the safety envelope was defined from
      an amusement park bumper-car impact. Each subject was restrained by a custom-fit
      lap and shoulder belt system and photo-reflective targets were attached to a
      tight-fitting cap worn on the head or adhered to the skin overlying skeletal
      landmarks on the head, spine, shoulders, sternum, and legs. A 3-D near-infrared
      target tracking system quantified the position of the following markers: head
      top, external auditory meatus, nasion, opisthocranion, C4, T1, T4, and T8.
      Trajectory data were normalized by subject seated height and head and spine
      rotations were calculated. The Generalized Estimating Equations method was used
      to determine the effect of age and key anthropometric measures on marker
      excursion. For all markers, the normalized forward excursion significantly
      decreased with age and all spinal markers moved upward due to a combination of
      rigid body rotation and spinal flexion with lesser upward movement with age. The
      majority of the spine flexion occurred at the base of the neck not in the upper
      cervical spine and the magnitude of flexion was greatest for the youngest
      subjects. Additional flexion occurred in the thoracic spine as well. Our findings
      indicate that the primary factor governing the differences in normalized head and
      spinal trajectories between the various age groups was decreasing head-to-neck
      girth ratio with increasing age. Other factors, such as muscle response and
      cervical vertebral structural properties, may also contribute to the differences,
      but were not evaluated in this paper. These results can serve as a data set for
      validating the responses of restrained ATDs and computational human models to low
      severity frontal collisions.

PMID- 20058561
TI  - Pediatric thoracoabdominal biomechanics.
AB  - No experimental data exist quantifying the force-deformation behavior of the
      pediatric chest when subjected to non-impact, dynamic loading from a diagonal
      belt or a distributed loading surface. Kent et al. (2006) previously published
      juvenile abdominal response data collected using a porcine model. This paper
      reports on a series of experiments on a 7-year-old pediatric post-mortem human
      subject (PMHS) undertaken to guide the scaling of existing adult thoracic
      response data for application to the child and to assess the validity of the
      porcine abdominal model. The pediatric PMHS exhibited abdominal response similar
      to the swine, including the degree of rate sensitivity. The upper abdomen of the
      PMHS was slightly stiffer than the porcine behavior, while the lower abdomen of
      the PMHS fit within the porcine corridor. Scaling of adult thoracic response data
      using any of four published techniques did not successfully predict the pediatric
      behavior. All of the scaling techniques intrinsically reduce the stiffness of the
      adult response, when in reality the pediatric subject was as stiff as, or
      slightly more stiff than, published adult corridors. An assessment of age-related
      changes in thoracic stiffness indicated that for both a CPR patient population
      and dynamic diagonal belt loading on a PMHS population, the effective stiffness
      of the chest increases through the fourth decade of life and then decreases,
      resulting in stiffness values approximately the same for children and for elderly
      adults. Additional research is needed to elucidate the generality of this finding
      and to assess its significance for scaling adult data to represent pediatric
      responses.

PMID- 20058562
TI  - The effect of angle on the chest injury outcome in side loading.
AB  - Thoracic injury criteria and injury risk curves in side impact are based on
      impactor or sled tests, with rigid or padded surfaces while airbags are very
      common on current cars. Besides, the loading is generally pure lateral while real
      crashes or regulations can generate oblique loadings. Oblique tests were found in
      the literature, but no conclusion was drawn with regard to the effect of the
      direction on the injury outcome. In order to address these two limitations, a
      series of 17 side airbag tests were performed on Post Mortem Human Subjects
      (PMHS) at different severities and angles. The subjects were instrumented with
      accelerometers on the spine and strain gauges on the ribs. They were loaded by an
      unfolded airbag at different distances in pure lateral or 30 degrees forward. The
      airbag forces ranged from 1680 N to 6300 N, the injuries being up to 9 separated
      fractured ribs. This paper provides the test results in terms of physical
      parameters and injury outcome of the 17 subjects. Geometrical and physical
      characteristics of the subjects are described as well as the distribution of
      injuries as a function of test conditions. Then a statistical analysis is
      presented which gives the effect of the loading angle on the injury outcome. The
      results of this study provide useful data for the validation of finite element
      models in terms of injury prediction, as well as for the development of injury
      risk curves for side impact dummies.

PMID- 20058563
TI  - ES2 neck injury assessment reference values for lateral loading in side facing
      seats.
AB  - Injury assessment reference values (IARV) predicting neck injuries are currently
      not available for side facing seated aircraft passengers in crash conditions. The
      aircraft impact scenario results in inertial loading of the head and neck, a
      condition known to be inherently different from common automotive side impact
      conditions as crash pulse and seating configurations are different. The objective
      of this study is to develop these IARV for the European Side Impact Dummy-2 (ES
      2) previously selected by the US-FAA as the most suitable ATD for evaluating side
      facing aircraft seats. The development of the IARV is an extended analysis of
      previously published PMHS neck loads by identifying the most likely injury
      scenarios, comparing head-neck kinematics and neck loads of the ES2 versus PMHS,
      and development of injury risk curves for the ES2. The ES2 showed a similar
      kinematic response as the PMHS, particularly during the loading phase. The ES2
      exhibited a stiffer response than the PMHS in the thoracic region, resulting in a
      faster rebound and smaller excursions in the vertical direction. Neck loads were
      consistent with results from previous authors and served as the basis for the ES2
      neck injury risk curve developed here. Regression analysis of the previously
      published PMHS neck loads indicated that the tension force at the occipital
      condyles was the only neck load component with a significant correlation (Pearson
      r2 = 0.9158) to AIS3+ classified injuries. Tension force in the ES2 upper neck
      showed a weaker but still significant correlation with injury severity (r2 =
      0.72) and is proposed to be used as an IARV with a tolerance of 2094 N for 50%
      AIS3+ risk. Although the prime focus of this study is on loading conditions
      typical in an aircraft crash environment, it is expected that the proposed IARV's
      can be used as an extension of typical automotive conditions, particularly for
      military vehicles and public transport applications where side facing upright
      seating configurations are more common.

PMID- 20058564
TI  - Injury risk curves for the WorldSID 50th male dummy.
AB  - The development of the WorldSID 50th percentile male dummy was initiated in 1997
      by the International Organisation for Standardisation (ISO/SC12/TC22/WG5) with
      the objective of developing a more biofidelic side impact dummy and supporting
      the adoption of a harmonised dummy into regulations. More than 45 organizations
      from all around the world have contributed to this effort including governmental
      agencies, research institutes, car manufacturers and dummy manufacturers. The
      first production version of the WorldSID 50th male dummy was released in March
      2004 and demonstrated an improved biofidelity over existing side impact dummies.
      Full scale vehicle tests covering a wide range of side impact test procedures
      were performed worldwide with the WorldSID dummy. However, the vehicle safety
      performance could not be assessed due to lack of injury risk curves for this
      dummy. The development of these curves was initiated in 2004 within the framework
      of ISO/SC12/TC22/WG6 (Injury criteria). In 2008, the ACEA- Dummy Task Force (TFD)
      decided to contribute to this work and offered resources for a project manager to
      coordinate of the effort of a group of volunteer biomechanical experts from
      international institutions (ISO, EEVC, VRTC/NHTSA, JARI, Transport Canada), car
      manufacturers (ACEA, Ford, General Motors, Honda, Toyota, Chrysler) and
      universities (Wayne State University, Ohio State University, John Hopkins
      University, Medical College of Wisconsin) to develop harmonized injury risk
      curves. An in-depth literature review was conducted. All the available PMHS
      datasets were identified, the test configurations and the quality of the results
      were checked. Criteria were developed for inclusion or exclusion of PMHS tests in
      the development of the injury risk curves. Data were processed to account for
      differences in mass and age of the subjects. Finally, injury risk curves were
      developed using the following statistical techniques, the certainty method, the
      Mertz/Weber method, the logistic regression, the survival analysis and the
      Consistent Threshold Estimate. The paper presents the methods used to check and
      process the data, select the PMHS tests, and construct the injury risk curves.
      The PMHS dataset as well as the injury risk curves are provided.

PMID- 20058565
TI  - Umbilical cord blood transplant--will it change the medical scenario in Malaysia?

PMID- 20058566
TI  - Pandemic influenza A (H1N1) 2009 in Malaysia--the next phase.

PMID- 20058567
TI  - Daytime sleepiness and sleep quality among Malaysian medical students.
AB  - Poor sleep quality and daytime somnolence is reported to be associated with
      cardiovascular events, road traffic accident, poor academic performance and
      psychological distress. Some studies documented that it is prevalent in most
      populations but its frequency among medical students has not been documented in
      Malaysia. This is a self-administered questionnaire survey of medical students
      from International Medical University, Malaysia. Daytime sleepiness of medical
      students was assessed using Epworth Sleepiness Scale (ESS). Student scoring ESS >
      11 was regarded as having excessive daytime sleepiness. Psychological distress
      was measured using 12-item General Health Questionnaire (GHQ-12). A total of 799
      medical students participated in this survey (response rate 69.5%). Daytime
      sleepiness occurred in 35.5%, psychological distress was present in 41.8% and
      16.1% reported bad sleep quality. Daytime sleepiness was significantly more
      common among the clinical students, those with self-reported bad sleep quality
      and psychological distress; but unrelated to the number of hours sleep at night.
      We have documented high prevalence of daytime sleepiness, poor sleep quality and
      psychological distress. Higher frequency among clinical students and the
      significant relationship with psychological distress suggest possible link to the
      stressful clinical training.

PMID- 20058568
TI  - Are Indians and females less tolerant to pain? An observational study using a
      laboratory pain model.
AB  - In Malaysia, it is a common belief among health care workers that females and
      Indians have lower pain threshold. This experience, although based on anecdotal
      experience in the healthcare setting, does not allow differentiation between pain
      tolerance, and pain expression. To determine whether there is a difference in the
      tolerance to pain between the three main ethnic groups, namely the Malays,
      Chinese and Indians as well as between males and females. This was a prospective
      study, using a laboratory pain model (ischaemic pain tolerance) to determine the
      pain tolerance of 152 IMU medical students. The mean age of the students was 21.8
      years (range 18-29 years). All of them were unmarried. The median of ischaemic
      pain tolerance for Malays, Chinese and Indians were 639s, 695s and 613s
      respectively (p = 0.779). However, statistically significant difference in
      ischaemic pain tolerance for males and females Indian students were observed.
      Possible ethnic difference in pain tolerance in casual observation is not
      verified by this laboratory pain model. Difference in pain tolerance between
      genders is shown only for Indians.

PMID- 20058569
TI  - Comparison between preloading with 10 ml/kg and 20 ml/kg of Ringer's lactate in
      preventing hypotension during spinal anaesthesia for caesarean section.
AB  - This prospective, randomized, study was designed to compare the effect of two
      different preloading volumes of Ringer's lactate for prevention of maternal
      hypotension induced by spinal anaesthesia for Caesarean section. Eighty ASA I or
      II obstetric patients were randomized to two groups. Group 1 (n = 40) received 20
      ml/kg of Ringer's lactate and Group 2 (n = 40) 10 ml/kg of Ringer's lactate over
      20 minutes before spinal anaesthesia. The lowest mean arterial pressure (MAP) for
      both groups were recorded at 15 minutes after giving spinal anaesthesia, This
      difference in the drop of MAP from base-line at 15 minutes (mean decrease of 12.5
      mmHg from baseline), between preloading with 10 ml/kg and 20 ml/kg of Ringer's
      was statistically significant. Twelve patients from Group 1 required bolus doses
      of ephedrine and 15% of these needed additional crystalloid whereas two patients
      from Group 2 needed ephedrine boluses and 22% of these required additional
      crystalloid. The difference in frequency of requirement for treatment of
      hypotension was not statistically significant. There were five patients in Group
      1 and six patients in Group 2 who experienced nausea and vomiting, the frequency
      of occurrence did not show any statistically significant difference between the
      two groups. In conclusion, for prevention of hypotension during spinal
      anaesthesia for Caesarean section, infusing 20 ml/kg or 10 ml/kg of Ringer's
      Lactate gave similar results and we do not recommend the use of a larger volume
      of crystalloid for preloading before spinal anaesthesia.

PMID- 20058570
TI  - Knowledge, attitude and vaccination status of varicella among students of
      Universiti Kebangsaan Malaysia (UKM).
AB  - Varicella is a highly infectious disease that can lead to severe complications
      such as pneumonia, encephalitis and death. Vaccination is the best method to
      prevent the disease. The objective of this study was to assess the level of
      knowledge, attitude and vaccination status of varicella among UKM students. A
      cross sectional study involving pre-tested questionnaires was undertaken between
      February and April, 2005. Questionnaires were distributed and filled by the first
      and second year students from four faculties in UKM (n = 879). The faculties
      included were divided into two categories: medical fields and non-medical fields.
      The results showed that the overall level of knowledge on varicella among
      respondents was intermediate. The score of knowledge was significantly higher
      among medical students (t = 10.9, p < 0.05) compared to non-medical students. The
      varicella vaccination coverage was low among UKM students (19.3%). The
      vaccination status was significantly higher among medical students compared to
      non-medical students (chi2 = 8.6, p < 0.05). Vaccination status of varicella
      among respondents had no association with the level of knowledge (chi2 = 2.42, p
      > 0.05). IN CONCLUSION: the awareness and vaccination status of varicella among
      UKM students were low. More varicella awareness programs should be held on
      universities' campuses to educate students on methods of prevention of this
      serious disease.

PMID- 20058571
TI  - Unrelated cord blood transplantation in children--a 10-year experience from UMMC.
AB  - Children who would benefit from a haematopoietic stem cell transplantation often
      lacked a compatible sibling donor. Unrelated cord blood transplantation was
      offered as an alternative donor source for patients with a variety of malignant
      and non-malignant diseases who had no further treatment options. Cord blood units
      were sourced from various international cord blood registries. The median
      nucleated and CD34+ cell doses were 8.7 x 10(7)/kg and 2.6 x 10(5)/kg
      respectively. In spite of adequate cell doses, a high rate of non-engraftment of
      32% was observed. Acute graft-versus-host disease (GVHD) occurred in 14 out of
      the 15 patients who engrafted with 53% being grade III to IV GVHD. The five year
      disease free survival was 40.7% with infection and GVHD being the commonest
      causes of death. The five year disease free survival was 20.5% and 60.7% for
      malignant and non-malignant diseases respectively.

PMID- 20058572
TI  - Ophthalmology inpatient consultation: does it make a difference to inpatient
      management?
AB  - Ophthalmology consultation is one of the commonest requested services for
      inpatients in a tertiary hospital. A total of 290 ophthalmology consultation
      requests were received over a period of six months (average 12 consultation
      requests per week) and from these, 222 patients were examined. The patient
      demographics, the hospitalization data, type of consultations (screening, new
      problem, preexisting problem), reasons for consultations and the ophthalmology
      diagnosis were determined. Out of 290 consultation requests, internal medicine
      services requested the highest number (95, 32.8%); the commonest type of
      consultation was screening for eye diseases (161, 55.5%) and the most common
      reason for consultation was to rule out diabetic retinopathy (125, 43.1%). The
      top five ophthalmology diagnoses after examination were diabetic retinopathy (45,
      20.3%), diabetic retinopathy ruled out (37, 16.6%), conjunctivitis (12, 5.4%),
      refractive error (11, 4.8%) and normal ocular examination (11, 4.9%). Inpatient
      ophthalmologic procedures were performed in 146 patients, the commonest of which
      was retinal laser photocoagulation. A total of 133 (59.9%) inpatients had a
      change in their management as a result of the ophthalmology consultation.

PMID- 20058573
TI  - Prevalence of depression and its associated factors among elderly patients in
      outpatient clinic of Universiti Sains Malaysia Hospital.
AB  - Depression among elderly primary care patients is a serious problem with
      significant morbidity and mortality. This is a cross sectional study to determine
      the prevalence of depression and its associated factors among the elderly
      patients attending the outpatient clinic, Universiti Sains Malaysia Hospital.
      This study utilized Malay version Geriatric Depression Scale 14 (M-GDS 14) to
      screen for elderly depression among Malaysian population. It also looked into
      associated risk factors for elderly depression using sociodemographic, family
      dynamics, and medically related questionnaires. Out of 244 subjects, 34 or 13.9%
      were found to have depression. Three variables were found to be significantly
      associated with depression. Elderly patient with any illness that limits the
      patient's activity or mobility has more risk of developing depression (OR 2.68 CI
      1.15 - 6.24). Elderly patients who were satisfied with their personal incomes (OR
      0.29 CI 0.10 - 0.85), and who had children or son/daughter-in-law to take care of
      them when they are sick (OR 0.10 CI 0.01 - 0.83) have a lower chance of having
      depression. Screening the elderly for depression, would help in diagnosing the
      elderly depression better and offer them the treatment needed.

PMID- 20058574
TI  - Proportion of dementia and its associated factors among elderly patients
      attending outpatient clinics of Universiti Sains Malaysia Hospital.
AB  - The increase in life expectancy observed over the last decade has particular
      relevance for conditions such as cognitive decline and dementia. This is a cross
      sectional study to determine the rate of dementia and to identify its associated
      factors among 399 elderly patients attending outpatient clinics of Universiti
      Sains Malaysia Hospital. This study was conducted in 2 phases. In the first
      phase, the literate subjects were screened using validated Malay version of Mini
      Mental State Examination (MMSE) and the illiterate subjects with Malay version of
      Elderly Cognitive Assessment Questionnaire (ECAQ). All subjects suspected to have
      dementia were selected for further evaluation in phase 2 of this study. The
      second phase involved full clinical examination in order to establish clinical
      diagnosis of dementia. The proportion of dementia in this study was 2.5% (10).
      Although history of exposure to pesticide (p < 0.05) and history of stroke (p <
      0.05) were significant, they were not significant factors. These were because
      vast discrepancy in number between those exposed to pesticide and having stroke
      between dementia and non dementia.

PMID- 20058575
TI  - The epidemiology and burden of childhood rotavirus infection in a tertiary
      hospital in Sabah, Malaysia.
AB  - We aimed to determine the epidemiology and burden of rotavirus (RV)
      gastroenteritis (GE) in children requiring hospital care in an urban setting in
      Sabah, Malaysia. A prospective study of all patients younger than 12 years of age
      admitted with acute GE to Queen Elizabeth Hospital, Sabah, over a six-month
      period (October 2005 to March 2006) was conducted. During the study period, a
      total of 167 children with acute GE who had stool samples examined for RV were
      studied. RV accounted for 16% of all diarrhoeal cases, and 1.7% of all admissions
      to the children's wards during the study period. There was no difference in
      severity of GE between RV and non-RV groups. RV infection is a common cause of
      childhood GE requiring hospital care in Sabah.

PMID- 20058576
TI  - A multicenter study in Malaysia to determine the efficacy and safety of a generic
      atorvastatin.
AB  - A multicenter study was conducted to assess the efficacy of a generic form of
      Atorvastatin (Ranbaxy's Storvas) in the treatment of Primary
      Hypercholesterolemia. One hundred and nineteen patients were given 10 mg of
      Storvas for four weeks and increased to 20 mg if target LDL-Cholesterol was not
      achieved. LDL-Cholesterol was reduced by 36.6% at four weeks and 37.5% at eight
      weeks from baseline. Total cholesterol and triglycerides were significantly
      reduced. There were no drug-related serious adverse events. We conclude that the
      generic atorvastatin is safe and effective in the treatment of primary
      hypercholesterolaemia and the results are comparable to published data on
      innovator atorvastatin.

PMID- 20058577
TI  - Outcome of patients presenting with idiopathic facial nerve paralysis (Bell's
      palsy) in a tertiary centre--a five year experience.
AB  - This is a retrospective study. The objective of this study is to review the
      factors influencing the outcome of treatment for the patients presented with
      idiopathic facial nerve paralysis. The demographic data, clinical presentation
      and management of 84 patients with idiopathic facial nerve paralysis (Bell's
      palsy) were collected from the medical record office, reviewed and analyzed from
      2000 to 2005. Thirty-four (72.3%) out of 47 patients who were treated with oral
      prednisolone alone, fully recovered from Bell's palsy meanwhile 36 (97%) out of
      37 patients who were treated with combination of oral prednisolone and acyclovir
      fully recovered. The difference was statistically significant. 42 (93.3%) out of
      45 patients who presented within three days to our clinic, fully recovered while
      28 (71.8%) out of 39 patients presented later then three days had full recovery
      from Bell's palsy. The difference was statistically significant. The outcome of
      full recovery is better with the patients treated with combined acyclovir and
      prednisolone compared with prednisolone alone. The patients who were treated
      after three days of clinical presentation, who were more than 50 years of age,
      who had concurrent chronic medical illness and facial nerve paralysis HB Grade IV
      to VI during initial presentation have reduced chance of full recovery of facial
      nerve paralysis.

PMID- 20058578
TI  - Long-term results of endoscopic resection of nasopharyngeal tumours.
AB  - Traditional open approaches to the nasopharynx either provide limited access and
      risk significant morbidity. Here we describe our experience with endoscopic
      resection of nasopharyngeal tumours. Retrospective chart review was performed for
      all patients who underwent endoscopic nasopharyngeal resection from September
      1993 to January 2007 at a tertiary rhinology centre. Six patients underwent
      endoscopic nasopharyngectomy for tumours arising from or involving the
      nasopharynx. The mean age was 49.8 years (range 23 - 70). The sex distribution
      was five males and one female. Four tumours were malignant and two were benign.
      The mean disease-free and overall survival for malignant tumors was 90.75 months
      (range 66 - 120 months). None of the benign tumors recurred. The endoscopic
      nasopharyngectomy technique may be successfully used for resection of tumors
      arising from or involving the nasopharynx with good efficacy and a decrease in
      morbidity when compared to open approaches.

PMID- 20058579
TI  - Treatment delay in rectal cancer.
AB  - Early diagnosis of rectal cancer is important for prompt treatment and better
      outcome. Little data exists for comparison or to set standards. The primary
      objective of this study is to identify factors resulting in delays in treatment
      of rectal cancer, the correlation between the disease stage and diagnosis waiting
      time, treatment waiting time and duration of symptoms. A five year retrospective
      audit was undertaken in University of Malaya Medical Centre (UMMC). There were
      137 patients recruited and the median time to diagnosis was nine days after the
      first UMMC Surgical Unit consultation with a mean of 18.7 days. Some 11% had to
      wait more than four weeks for diagnosis. The median time from confirmation of
      diagnosis to surgery was 11 days with a mean of 18.6 days. Sixty-two percent of
      patients were operated upon within two weeks of diagnosis and more than 88% by
      four weeks. However, 10% of them had delayed surgery done four weeks after
      diagnosis. Long colonoscopy waiting time was the main cause for delay in
      diagnosis while delay in staging CTs were the main reason for treatment delays.

PMID- 20058580
TI  - Vancomycin treatment failure in a vancomycin susceptible methicillin-resistant
      Staphylococcus aureus (MRSA) infected patient.
AB  - A 64-year old patient, who had bacteraemia, did not respond to vancomycin despite
      the MRSA isolate being sensitive to the antibiotic at MIC 2 microg/mL. Electron
      microscopy of the MRSA isolate showed thickening of the cell wall, which was not
      observed in MRSA with lower vancomycin MIC.

PMID- 20058581
TI  - Adult pyloric stenosis masquerading as acute renal failure.
AB  - Gastric outlet obstruction and in particular, pyloric stenosis, is relatively
      common in developing countries. Acute clinical presentation is often the
      manifestation of biochemical and electrolyte changes. The presence of metabolic
      alkalosis in combination with acute renal failure should alarm us to the
      possibility of adult pyloric stenosis. We report a case of adult pyloric stenosis
      that presented as acute renal failure and discuss its pathophysiology.

PMID- 20058582
TI  - Handlebar herniation: a case of near missed abdominal injury.
AB  - Timely identification of specific injuries in a polytrauma case is of paramount
      importance in order to reduce morbidity and mortality. Unfortunately, some of
      these injuries are subtle and can be missed on initial primary and secondary
      assessments. In this paper, we report one such injury in a case of a 16-year old
      motorcyclist who complained of abdominal pain over the right lumbar region after
      the motorcycle handlebar hit his abdomen. Although initial assessment was
      uneventful, he was subsequently diagnosed to have a traumatic abdominal wall
      herniation on abdominal computed tomography after more than 24 hours of
      observation in the ward.

PMID- 20058583
TI  - Parotid abscess: an unusual cause of facial nerve palsy.
AB  - Facial nerve palsy with a parotid mass is usually associated with malignant
      neoplasm of parotid gland. Its occurrence as a complication of parotid abscess is
      extremely rare. A literature review revealed only 16 cases of facial nerve palsy
      associated with suppurative parotitis or parotid abscess were reported. We
      present a case of deep parotid abscess which is complicated by facial nerve
      dysfunction. Underlying neoplasia was excluded.

PMID- 20058584
TI  - Leiomyosarcoma of the maxillary sinus.
AB  - Leiomyosarcoma is a malignant smooth-muscle tumour that has a predilection for
      the gastrointestinal and female genital tract. It is locally fast-spreading and
      highly aggressive, and the prognosis is poor. We report a rare case of
      leiomyosarcoma of the maxilla in a patient who sought treatment for maxillary
      swelling, nasal obstruction with no epistaxis, orbital involvement or cervical
      lymph node metastasis. The patient underwent subtotal maxillectomy followed by
      radiotherapy. At present, he is symptom free with no recurrence and under regular
      follow up.

PMID- 20058585
TI  - Post viral acute multifocal posterior placoid pigment epithiopathy in a teenage
      child.
AB  - We report a rare case of a young boy presenting with bilateral blurring of vision
      following a viral like illness. Fundus examination revealed multiple pale cream
      coloured lesions scattered across the posterior pole of both eyes. Fundus
      fluorescein angiography showed characteristic features of early hypofluorescence
      and late hyperfluorescence, further confirming the diagnosis of acute posterior
      placoid pigment epitheliopathy (AMPPPE). He was treated with topical steroids for
      the accompanying mild anterior uveitis. He had a prompt visual recovery with no
      adverse sequelae.

PMID- 20058586
TI  - A complete transection of larynx.
AB  - Acute laryngeal injury is a rare, potentially lethal injury. It often poses
      difficulty in airway management. Commonly described are external laryngeal or
      blunt injuries. We report a case of penetrating neck injury resulting in complete
      transection of cricoid cartilage. A lady presented with a large, deep slash wound
      in her neck from a knife injury. There was complete laryngotracheal separation.
      The airway was secured before she was taken to the operating theatre. A
      tracheostomy was performed. Exploration revealed the cricoid ring was cut
      horizontally into two. Anastomosis of the cartilaginous framework was undertaken.
      Fibreoptic laryngoscopy showed bilateral vocal cords paralysis. After two months
      the patient recovered without airway compromise, she regains her voice. Repeat
      laryngoscopy showed good mobility of the vocal cords. In conclusion surgical
      reconstruction should be meticulously done to ensure good respiratory and
      phonatory abilities.

PMID- 20058587
TI  - Puffer fish poisoning: a family affair.

PMID- 20058589
TI  - [Application of new techniques and products in lumbar spinestumbles and
      challenge].

PMID- 20058588
TI  - End stage renal failure mimicking as acute renal failure in developing countries.

PMID- 20058590
TI  - [Anterior multilevel corpectomy for the treatment of severe ossification of
      posterior longitudinal ligament in the cervical spine].
AB  - OBJECTIVE: To discuss the surgical indications, outcomes and complications of
      anterior multilevel corpectomy for the treatment of severe ossification of
      posterior longitudinal ligament (OPLL) in the cervical spine. METHODS: Between
      April 2006 and March 2008, a total of 25 patients (20 males and 5 females, age
      range: 42 - 75 yr, mean: 53. 2 yr) underwent anterior multilevel corpectomy for
      severe ossification of posterior longitudinal ligament in the cervical spine.
      Radiological studies showed that the type of OPLL was distributed as follows: 7
      local, 5 segmental, 8 continuous and 5 mixed. The OPLL extended an average of 2.
      8 vertebrae (2 - 4) and the stenotic rate of spinal canal was 68.4% (50% - 97%).
      After corpectomy and removal of OPLL, titanium mesh cage and anterior plate were
      employed to restore cervical stability in all patients. RESULTS: Among these
      patients, 16 underwent two-level corpectomy and 9 three-level corpectomy. After a
      follow-up of 2 - 18 months, the mean JOA score increased from 9. 3 (5 - 12)
      points pre-operation to 14.2 (11 - 16) points post-operation. The mean
      improvement rate of neurological status was 63.2% (22.2% - 87.5%). The
      complications included CSF leakage in 6 cases (intermittent CSF pseudocyst in 4),
      nerve root palsy in 2, hematoma in 1 and transient neurological deterioration in
      1. CONCLUSION: Anterior multilevel corpextomy can achieve a better clinical
      outcome in the treatment of severe cervical ossification of posterior
      longitudinal ligament. But it is technically demanding and carries a higher risk.

PMID- 20058591
TI  - [Correlation between magnetic resonance T2-weighted increased signal intensity
      position and prognosis of cervical spondylotic myelopathy].
AB  - OBJECTIVE: To investigate the correlation between position of the spinal cord
      with increased signal intensity (ISI) on magnetic resonance images (MRI) and the
      outcome of surgical treatment for cervical spondylotic myelopathy (CSM). METHODS:
      Seventy-two patients with CSM who underwent preoperative MRI were selected. Pre-
      and post-operative clinical status was evaluated by modified Japanese Orthopedic
      Association (JOA) score. ISI was evaluated according to the T2-weighted
      sequences. The JOA score and the recovery ratios among patients with ISI in gray
      matter (group A), in both gray and white matter (group B) and ISI-negative group
      were compared. RESULTS: Forty patients were in ISI-negative group. ISI presenting
      only in gray matter included 21 cases (group A) and 11 cases were in both gray
      and white matter group (group B). Preoperative JOA score of ISI positive and
      negative group had significant difference, but the recovery ratios had no
      significant difference [recovery ratios of two groups at week 1, week 14, and
      week 52 were (20.8 +/- 14.5)%, (51.1 +/- 15.6)%, (60.1 +/- 14.2)% and (20.3 +/-
      14.3)%, (54.4 +/- 22.3)% and (61.2 +/- 22.3)% respectively; P > 0.05]. The
      recovery ratios of negative group and group A in week 104 were superior to group
      B [recovery ratios of negative group, group A, and group B in week 52 were (61.2
      +/- 22.3)%, (64.3 +/- 13.3)% and (50.1 +/- 11.2)% respectively; P < 0.05].
      CONCLUSION: Patients with ISI in the gray matter alone on T2-weighted MR images
      have no significantly different surgical outcomes as compared with those without
      ISI. Patients with ISI in both gray and white matter have worse surgical outcomes
      than those without ISI.

PMID- 20058592
TI  - [Natural history and prognosis of discogenic low back pain].
AB  - OBJECTIVE: To understand the natural history and prognosis of patients with
      discogenic low back pain so as to offer a better guide on its clinical treatment.
      METHODS: From December 2003 to November 2004, we consecutively hospitalized 72
      patients with discogenic low back pain diagnosed by lumbar discography. These
      patients were randomized into two groups. One group (n = 36) received an
      intradiscal methylene blue (MB) injection immediately after discography while
      another group (n = 36) received a placebo. Both Visual Analog Scale (VAS) and
      Oswestry Disability Index (ODI) were used to assess the back pain symptoms and
      the lumbar function respectively during a 4-year follow-up period. RESULTS: In
      total, 32 of 36 patients who received a placebo injection underwent a 4-year
      follow-up. Of these patients, 4 cases (12.5%) had their low back pain symptoms
      alleviated, 1 case (3.1%) slightly improved, 3 cases (9.4%) aggravated and 22
      cases (68.8%) had no change in symptoms. According to VAS and ODI scores taken at
      different time points, these two scores gradually decreased over time; however,
      no statistical significances were found (VAS: F = 3.049, P > 0.05; ODI: F = 2.
      272, P > 0.05). CONCLUSION: The disease course of discogenic low back pain is
      chronic and persistent so that its symptoms show no improvement over time.

PMID- 20058593
TI  - [Quality of vision in patients with aspherical diffractive multifocal intraocular
      lens implantation].
AB  - OBJECTIVE: To evaluate the visual performance of patients with Tecnis ZM900
      aspherical diffractive multifocal intraocular lens (MIOL) as compared with
      aspherical monofocal intraocular lens (IOL). METHODS: A prospective nonrandomized
      controlled study was conducted. Consecutively 114 senile cataract patients (114
      eyes) received phacoemulsification and IOL implantation, 57 patients (57 eyes)
      were implanted Tecnis ZM900 MIOL (multifocal group) and 57 patients (57 eyes)
      were implanted aspherical Tecnis ZA9003 IOL (monofocal group). All patients were
      assessed at 3 months postoperatively: uncorrected and best corrected visual
      acuities for distance and near, distance corrected near visual acuity, higher
      order aberrations of IOL, modulation transfer function, contrast visual acuity at
      different contrast levels and different distance (40 cm, 63 cm and 100 cm) and
      pseudoaccommodation. Patient satisfaction (spectacle independence, photic
      phenomena and overall satisfaction) was assessed by a questionnaire. RESULTS: At
      3 months post-operation, both uncorrected near visual acuity and distance
      corrected near visual acuity were significantly better in multifocal group than
      monofocal group (t = - 7.62, - 9.89, P < 0.05). The accommodative range was (4.74
      +/- 1.05) D in multifocal group and (1.65 +/- 0.68) D in monofocal group (P <
      0.01). There was no statistically significantly difference between the two groups
      in IOL higher-order aberration with different pupil sizes (3 mm vs 5 mm). At the
      distance of 40 cm and 63 cm, visual acuity scores were higher in multifocal group
      than in monofocal group (P < 0.01). Modulation transfer function was similar in
      the two groups and there was no statistically significantly difference. The
      spectacle independence was 85.9% in multifocal group versus 24.6% in the
      monofocal group (chi2 = 43.46, P < 0.05). CONCLUSION: Compared with aspherical
      monofocal IOL, the Tecnis ZM900 aspherical diffractive MIOL not only provided
      certain pseudoaccommodation with a better useful near visual acuity, but also
      provided a better quality of vision, resulting in higher levels of spectacle
      independence and patient satisfaction.

PMID- 20058594
TI  - [Efficacy of enalapril combined with folic acid in lowering blood pressure and
      plasma homocysteine level].
AB  - OBJECTIVE: To investigate the efficacy of enalapril combined with folic acid in
      lowering both blood pressure and plasma total homocysteine (Hcy) in essential
      hypertensive patients. METHODS: A randomized, community-based clinical trial was
      conducted. Subjects with hypertension were randomly assigned to one of three
      treatment groups:enalapril 10 mg/d alone (control), enalapril 10 mg plus folic
      acid 0.4 mg daily (low-dose group) and enalapril 10 mg combined with folic acid
      0.8 mg daily (high-dose group) for a total of 8 weeks. Resting blood pressures of
      all subjects was measured at baseline, 2nd, 4th, 6th and 8th week of therapy.
      Plasma Hcy levels were measured at baseline, 4 week and the end of study.
      RESULTS: A total of 273 hypertensive patients were enrolled. All analyses were
      performed according to the intention to treat. Compared with control group, both
      low- and high-dose group had significantly a greater efficacy in lowering both
      blood pressure and plasma Hcy level, or in lowering either blood pressure or
      plasma Hcy level, or in lowering Hcy level. The proportion of subjects showing a
      marked reduction in both blood pressure and plasma homocysteine in control group,
      low-dose group and high-dose group were 3.8%, 15.2% and 17.1% respectively; the
      proportion of subjects showing a marked reduction in either blood pressure or
      plasma homocysteine in control group, low-dose group and high-dose group were
      43.8%, 70.9% and 58.5% respectively. Effect upon blood pressure lowering was not
      significantly different among these three regimens. CONCLUSION: As compared to
      enalapril alone, enalapril combined with folic acid showed a better efficacy in
      reducing both blood pressure and plasma Hcy level in hypertensive subjects.

PMID- 20058595
TI  - [Serum proteomics profiling for diagnosis of myasthenia gravis].
AB  - OBJECTIVE: To identify the significant protein peaks and establish the diagnostic
      model of myasthenia gravis (MG) by serum proteomics profiling analysis. METHODS:
      The serum samples from 56 MG patients and 16 healthy controls were detected by
      the technology of surface-enhanced laser desorption ionization time-of-flight
      mass spectrometry (SELDI-TOF MS). The differentially expressed protein peaks were
      identified to establish a MG diagnostic model. And preliminary validation was
      performed. RESULTS: Thirty-eight specific protein peaks with significant
      differences were found in the serum protein pattern of 56 MG patients and 16
      healthy controls. Systemic optimization identified 2 protein peaks of M4168.94
      and M1122.57. And they were used to build the MG diagnostic model of
      differentiating 56 cases from 16 controls. CONCLUSION: The serum protein
      profiling can be a novel, effective and sensitive tool to screen for MG-related
      protein peaks and establish a diagnostic model.

PMID- 20058596
TI  - [Study of the best embryo transfer strategy in frozen-thawed embryo transfer
      cycle].
AB  - OBJECTIVES: To study the relationship of the number and quality of embryos
      transferred with clinical pregnancy rate and multiple pregnancy rate in frozen
      thawed embryo transfer (FET) cycle. METHODS: Retrospective analysis of the
      clinical data of 995 FET cycles. Patients were stratified as age < 35 or > or =
      35, Both groups' clinical pregnancy rate and multiple pregnancy rate were
      compared according to the number of embryos and high-quality embryos transferred.
      RESULTS: (1) The clinical pregnancy rates were 50.0%, 56.6% and 56.5%, and twin
      pregnancy rates were 6.3%, 43.8% and 30.6% respectively in < 35 group when one,
      two or three embryos were transferred. There is not any significantly statistic
      difference among these subgroups (P > 0.05). However, the twin pregnancy rate in
      one-embryo transferred subgroup was significantly lower than that of two-embryo
      transferred subgroup (P < 0.05). Moreover, the clinical pregnancy rate was not
      different among single high-quality embryo transferred subgroup and other high
      quality embryo transferred subgroups, the multiple pregnancy rate was lower than
      the others. (2) The clinical pregnancy rates were 0, 47.3% and 53.8%, and twin
      pregnancy rates were 0, 25.7% and 25.7% respectively in > or = 35 group when one,
      two or three embryos were transferred. The clinical pregnancy rate and twin
      pregnancy rate between two-embryo and three-embryo transferred subgroups were not
      significantly different (P > 0.05). Moreover, the clinical pregnancy rate was not
      different among two-embryo transferred containing one high-quality embryo
      subgroup and other high-quality embryo transferred subgroups, the multiple
      pregnancy rate was lower than the others. CONCLUSIONS: There is a close
      relationship between the number and quality of embryos transferred and clinical
      pregnancy rate, multiple pregnancy rate in FET cycles. For the patient aged < 35,
      we recommend performing single high-quality embryo transfer in order to reduce
      the multiple pregnancy. For the patient aged > or = 35, two-embryo transfer
      containing one high-quality embryo is enough to obtain a satisfied clinical
      pregnancy rate and an acceptable multiple pregnancy rate.

PMID- 20058597
TI  - [Effects of different fertilizations upon serum HCG level of IVF versus ET in
      early pregnancy].
AB  - OBJECTIVE: To compare the serum HCG levels in pregnant women of routine IVF
      versus ICSI during fresh transplantation cycles so as to explore whether ICSI
      influenced the serum HCG levels. METHODS: A total of 934 IVF pregnant cycles
      during March 2005 to September 2006 were divided into 7 groups: biochemical
      pregnancy (A), first-trimester miscarriages (B), ectopic pregnancy (C), single
      pregnancy (D), twin-pregnancy (E), triplet-pregnancy (F) and heterotopic
      pregnancy (G). The median of serum HCG level at Days 14 and 21 was calculated
      among 7 groups. RESULTS: The serum HCG value was lower by ICSI than that by IVF
      only in biochemical pregnancy group at Day 14 (P = 0. 032). CONCLUSION: ICSI is
      associated with relatively low HCG values in the biochemical pregnancies at Day
      14 after embryo transplantation. There is no statistical difference of HCG level
      for clinical pregnancy between IVF and ICSI.

PMID- 20058598
TI  - [The role of early hepatic artery ischemia on biliary complications after liver
      transplantation and hepatic arterial interventional therapy].
AB  - OBJECTIVE: To explore the influence of early hepatic artery ischemia on the
      occurrence and prognosis of biliary complications after orthotopic liver
      transplantation (OLT), and the value of early hepatic arterial interventional
      therapy. METHODS: In the 720 recipients who received OLT in our hospital from
      October 2003 to June 2007, 32 cases were detected hepatic artery stenosis (HAS,
      30 cases) or hepatic artery thrombosis (HAT, 2 cases) by color Doppler Ultrasound
      from 4 to 65 days (mean, 25 +/- 15) after OLT. All of them were confirmed by DSA
      and/or CT angiography. Of the 32 patients, 20 were treated by hepatic arterial
      interventional therapy. The end-point of follow-up was the time of patient's
      death and retransplantation. RESULTS: In this study, 20 cases developed biliary
      complications, including the common bile duct stenosis in 2 cases, intra- and
      extra hepatic bile duct stenosis in 13 cases and multiple intrahepatic bile duct
      stenosis in 5 cases. Among them, 2 patients complicated with bile leakage, 4 with
      biloma and 3 with liver abscess. Of the 20 patients, 8 with HAS received
      successful hepatic arterial interventional therapy which was performed two weeks
      after HAS detected; 10 with HAS didn't receive hepatic arterial interventional
      therapy; 1 with HAT received successful thrombolysis; 1 with HAS received failed
      hepatic artery stent implantation. During a median follow-up of 262 days (range,
      22 -517 days), 10 patients died, 6 underwent retransplantation, and the other 4
      survived; cumulated survival rates at 6, 12 and 24 months were 60.0%, 34.9% and
      0, respectively. 12 cases didn't develop biliary complications. Nine of them
      received successful hepatic arterial interventional therapy within 2 weeks HAS
      detected, 2 with acute rejection received flushing anti-rejection therapy, 1 with
      HAT received retransplantation because of unsuccessful thrombolysis. During a
      median follow-up of 952 days (range, 14 - 1398 days), 3 patients died, 1
      underwent retransplantation, and the other 8 survived; cumulated survival rates
      at 6, 12 and 24 months were 75%, 66.7% and 66.7%, respectively. CONCLUSION: Early
      hepatic artery ischemia after OLT is an important agent for biliary
      complications. Early and successful hepatic arterial interventional therapy
      helped to reduce the incidence of biliary complications and improve the patients'
      prognosis.

PMID- 20058599
TI  - [Preoperative chemotherapy for long-term results of small cell lung cancer].
AB  - OBJECTIVE: To reveal the pre-operative chemotherapy for long-term of small cell
      lung cancer. METHODS: From January 1994 to January 2005, 263 patients with small
      cell lung cancer underwent combined therapy. The comparison of long-term survival
      rates was made between pre-operative chemotherapy group (n = 111) (group A) and
      post-operative chemotherapy (n = 96) (group B). RESULTS: The analyses disclosed
      that the overall 5-year survival rate was 42.16%. The 5-year survival rate of
      group A was 38.25% while in group B it was 46.57%. 5-year survival rate of group
      A for N0-1 and N2 was 40.12% and 39.22%, that for stage I, II, IIIa, IIIb, IV was
      60.15%, 35.70%, 40.16%, 14.29% and 0 respectively. 5-year survival rate of group
      B for N0-1 and N2 was 51.91% and 42.69%, that for stage I, II, IIIa, IIIb, IV was
      61.1%, 50.23%, 42.32%, 26.47% and 0 respectively. CONCLUSION: The comparison of
      the survival rate between patients with the pre-operative chemotherapy and those
      with chemotherapy post-operatively revealed trend of variation. Operation plus
      post-operative chemotherapy mode is indispensable for better prognosis of small
      cell lung cancer.

PMID- 20058600
TI  - [Effect of monoclonal or different cell seeding densities on the differentiation
      potential of immortalized human mesenchymal stem cells in vitro and in vivo].
AB  - OBJECTIVE: To determine whether monoclonality or different cell seeding densities
      could influence the differentiation potential of immortalized human mesenchymal
      stem cells (hMSC-TERT) and to find an effective cultural method of hMSC-TERT in
      vitro. METHODS: From the parental hMSC-TERT cell line, we derived 30 monoclonal
      cell lines and two independent cell lines based on different plating densities
      during expansion in culture. Their adipocytic, osteogenic, neuronal
      differentiation potential in vitro and multidirectional differentiation potential
      in vivo were analyzed by immunohistochemistry for pathologic tissue markers.
      RESULTS: Monoclonal cell lines and the cell line derived at low seeding density
      had a lower differentiation potential in vitro than the cell line derived at
      higher cell seeding density. The differentiation potential of monoclonal hMSC
      TERT cells were dissimilar. Some of monoclonal hMSC-TERT lines expressed
      epithelial differentiation potential in vivo while the parental hMSC-TERT cells
      line did not. CONCLUSION: Multiclonal hMSC-TERT cells cultured in high seeding
      density can keep the differentiation potential, cloning the hMSC-TERT cells
      before transplantation to find the special clones for special purpose of
      transplantation.

PMID- 20058601
TI  - [Role of central neuronal nicotinic receptor in the inhibitory effect of
      isoflurane on synaptic long-term potentiation in hippocampal slices of rats].
AB  - OBJECTIVE: To determine effect of central neuronal nicotinic receptor on synaptic
      long-term potentiation (LTP) in the CA1 area of rats hippocampal slices. METHODS:
      Brain slice preparation transverse hippocampal slices were obtained from male
      Sprague-Dawley rats that were ether-anesthetized and decapitated. The hippocampus
      was rapidly removed, and slices were prepared in ice-cold artificial
      cerebrospinal fluid (ACSF), oxygenated with 95% O2 - 5% CO2. Seventy-seven slices
      were randomly divided into 11 equal groups (n = 7 each): group LTP; group
      isoflurane 0.125; group isoflurane 0.25; group isoflurane 0.5; group nicotine
      0.1; group nicotine 1.0; group nicotine 10.0; group nicotine 1.0 + isoflurane
      0.25; group nicotine 10.0 + isoflurane 0.25; group mecamylamine; group
      mecamylamine + isoflurane 0.125. One recording electrode was positioned in the
      pyramidal cell layer of the CA1 area of rats hippocampal slices to simultaneously
      record evoked population spikes (PS). For LTP induction, high-frequency
      stimulation (HFS) conditioning pulses (100 Hz/s) were applied to the Schaffer
      collateral-commissural pathway of hippocampus using a bipolar stimulating
      electrode. The changes of PS amplitude after HFS were analyzed in each group.
      RESULTS: The PS amplitude of the rats hippocampal slices in group LTP after HFS
      was significantly increased by (52 +/- 12)% compared with that of pre-HFS
      indicating the successful induction of LTP. Compared with group LTP, the PS
      amplitudes decreased significantly in group isoflurane 0.125, 0.25 and 0.5 after
      HFS (P < 0.01) and increased significantly in group nicotine 1.0 and 10.0 (P <
      0.01), but the PS amplitudes in group nicotine 0.1 was not significantly changed
      after HFS (P > 0.05). The PS amplitudes after HFS in group nicotine 1.0 +
      isoflurane 0.25 and group nicotine 10.0 + isoflurane 0.25 was dramatically
      increased compared with the value of group isoflurane 0.25 (P < 0.01), but did
      not differ significantly from group LTP (P > 0.05). The PS amplitudes after HFS
      in group mecamylamine has no significant difference compared with the value of
      group isoflurane 0.125, but it was significantly lower than that in group LTP (P
      < 0.01). The PS amplitudes after HFS in group mecamylamine + isoflurane 0.125
      significantly decreased compared with the value of group isoflurane 0.125 and
      group LTP (P < 0.05 or P < 0.01). CONCLUSION: The inhibition of LTP induction may
      contribute to isoflurane-induced deficits in memory, and the underlying mechanism
      is involved in the inhibition of nicotinic acetylcholine receptor activation in
      hippocampus of rats.

PMID- 20058602
TI  - [Correlation between MR diffusion weighted imaging with malignant degree of
      rabbit liver VX2 tumor models].
AB  - OBJECTIVE: To investigate the correlation between MR diffusion weighted imaging
      with cellularity and PCNA-LI of rabbit liver VX2 tumor models in different
      periods. METHODS: 38 successful implanted rabbits were assigned randomly into 2
      equal groups and were performed MR DWI in different periods (14 and 21 d) after
      implantation respectively. Specimens of all tumors were stained with HE and PCNA
      LI after MR examination. RESULTS: (1) The ADC value (x 10(-3) mm2/s) in
      surrounding solid components of liver VX2 tumors in the group of 21 d was lower
      than that of the group of 14 d (0.77 +/- 0.19 vs 1.00 +/- 0.24, P = 0.007); (2)
      the cellularity and PCNA-LI in surrounding solid components of liver VX2 tumors
      in the group of 21 d were higher than those of the group of 14 d respectively
      (63% +/- 7% vs 43% +/- 10%, P = 0.011; 80% +/- 11% vs 56% +/- 8%, P = 0.008); (3)
      there were negative correlation between ADC value and cellularity, PCNA-LI of the
      solid components of the tumors (r = - 0.695, P = 0.000; r = -0. 698, P = 0.000).
      CONCLUSION: The cellularity may be the most important factor that affects ADC
      value in solid components of liver VX2 tumors. Since the degree of malignancy is
      closely connected with cellularity and PCNA labeling index, ADC value measurement
      may be a new method which could predict the degree of malignancies in vivo.

PMID- 20058603
TI  - [Role of nitric oxide in pathogenesis of cold nerve injury].
AB  - OBJECTIVE: To study the role of nitric oxide (NO) in the pathogenesis of cold
      nerve injury and to explore its mechanism. METHODS: Cold nerve injury model was
      established in rat's sciatic nerve. Consistent and intermittent cooling of 4
      degrees C for 2 hours were respectively applied to the sciatic nerves. Nerve
      samples were taken at different time points: immediately post-cooling and 4 h, 1
      d & 3 d post-cooling. The group of aminoguanidine (AG) intervention was also
      established. Then NO levels in the nerves and blood serum were detected. Induced
      nitric oxide synthase (iNOS) in ganglion was determined by immunohistochemistry.
      Morphology of cooled sciatic nerves in the AG groups (consistent & intermittent
      cooling AG groups) and control groups (1 d time point of consistent &
      intermittent cooling groups) was observed by light microscope and electron
      microscope. RESULTS: At the time points of immediacy, 4 h, 3 d in the consistent
      cooling groups and the time points of immediacy, 4 h, 1 d in the intermittent
      cooling groups, different incremental degrees of NO levels in the cooled nerves
      (0.146 +/- 0.047), (0.216 +/- 0.048), (0.137 +/- 0.035), (0.154 +/- 0.027),
      (0.260 +/- 0.027), (0.218 +/- 0.042) micromol/g as compared with those of
      controls (0.098 +/- 0.022), (0.158 +/- 0.030), (0.085 +/- 0.020), (0.127 +/-
      0.016), (0.72 +/- 0.027), (0.174 +/- 0.026) micromol/g, P < 0.01, P < 0.05). And
      NO levels in the cooled nerves at the time points of 4 h, 1 d, 3 d in the
      intermittent cooling groups were higher than those in the consistent cooling
      groups (P < 0.01, P < 0.05). NO levels in blood serum at the time points of
      immediacy and 1 d in the intermittent cooling groups (4.98 +/- 1.33) micromol/L,
      (4.02 +/- 0.68) micromol/L were higher than those in the consistent cooling
      groups (2.47 +/- 0.36) micromol/L, (3.00 +/- 0.67) micromol/L, P < 0.01). Both in
      consistent cooling and intermittent cooling groups, different incremental degrees
      of areas and integrated optical density (IOD) of iNOS positive staining in
      ganglions were found in cooled side as compared with the control side at
      different time points (P < 0.01, P < 0.05, P > 0.05), while those at the time
      point of immediacy in the intermittent cooling groups (131 686 +/- 24 549) , (4.1
      +/- 0.13) x 10(9) were higher than those in the consistent cooling groups (78 558
      +/- 34 849), (2.1 +/- 0.93) x 10(9), P < 0.05. NO level of cooled nerves in the
      intermittent cooling AG group (0.178 +/- 0.030) micromol/g was lower than those
      at the time point of 1 d in intermittent cooling groups (0.218 +/- 0.042)
      micromol/g, P < 0.05). Also a reduction of NO levels of blood serum, areas and
      IOD of iNOS positive staining was found in the AG groups as compared with the
      control groups (P < 0.05) while the reduction was more significantly found in the
      intermittent cooling AG group (P < 0.01, P < 0.05). Through light microscope and
      electron microscope, more severe pathological injury of cooled nerve was seen in
      the intermittent cooling group as compared with 1d time point of the consistent
      cooling groups, and a marked reduction of pathological injury was found when AG
      was administered. It was also more significant in the intermittent cooling AG
      group. CONCLUSION: NO plays a causative role in the pathogenesis of cold nerve
      injury, especially in intermittent cold nerve injury. The expression of iNOS is
      the main source of NO. Production of free radicals and the resulting toxic injury
      may be its main mechanism.

PMID- 20058604
TI  - [Expression of metabotropic glutamate receptor 5 in spinal cord of morphine
      tolerant rats].
AB  - OBJECTIVE: To investigate the expression of metabotropic glutamate receptor 5
      (mGluRS) in spinal cord of morphine tolerant rats and understand the influence of
      mGluR5 antagonist MPEP upon the expression of mGluRS. METHODS: Male Sprague
      Dawley rats were randomly divided into four groups with 8 rats each:control group
      (NS), morphine group, morphine plus MPEP group and MPEP group. A morphine
      tolerance model of rat was established by repeated administration of 10 microg
      morphine intrathecally twice daily for 7 days. The effects of morphine co
      administrated with MPEP upon the thermal pain threshold were examined by tail
      flick test. Tail flick latency (TFL) was measured at 30 min pre- and postdosing.
      MPE% (percentage of maximal possible effect) was calculated by the equation: MPE
      (%) = [(test response time-basal response time)/(cut-off time-basal response
      time)] x 100%. The rats were sacrificed and L4-5 spinal cord tissue was removed.
      The expression of mGluR5 in every group was examined by immunofluorescence and
      Western blot. RESULTS: MPE% of morphine group decreased gradually after chronic
      administration of morphine intrathecally. There was no significant difference
      between morphine group and control group at Day 7 (P > 0.05). Morphine plus MPEP
      group had significant analgesic effect as compared with morphine group at Day 7
      (P < 0.05). The expression of mGluR5 was up-regulated in the dorsal horn of
      spinal cord in morphine tolerant rats. The protein level of mGluRS in morphine
      plus MPEP group was lower than that in morphine group (P < 0.05), but higher than
      control group (P < 0.05). CONCLUSION: The mGluR5 antagonist MPEP can prevent the
      development of morphine tolerance. The expression of mGluR5 protein increases in
      the spinal cord of morphine tolerant rats. MPEP plays its role in morphine
      tolerance by partly inhibiting the expression of mGluRS.

PMID- 20058605
TI  - [Comparative study on the immunogenicity of human homologous cardiac valve and
      great artery homograft cryopreserved with liquid nitrogen].
AB  - OBJECTIVE: To study the differences on the immunogenicity of the leaflets,
      arterial wall and myocardium of conduit valved homograft (CVH) cryopreserved with
      liquid nitrogen. METHODS: Mono-cell suspension of leaflets cells and arterial
      cells of CVH were respectively co-cultured with human lymphatic cells whose blood
      groups were the same with that of CVH donors. Expressive levels of CD25 and HLA
      DR of these lymphatic cells were detected by flow cytometry in the different
      cultural duration and compared with that of lymph cells alone cultured
      (comparative group). RESULTS: The immunogenicity of CVH artery walls was more
      severe than that of CVH leaflets, and expressive level of whose CD25 and HLA-DR
      was higher. The immunogenicity of CVH myocardium was not studied because the
      myocardial cell suspension were not be acquired in this study. CONCLUSION: It is
      proved that in vitro experimental study that the immunogenicity of arterial walls
      of cryopreserved CVH is more severe than that of leaflets.

PMID- 20058606
TI  - [Focus on standardized diagnosis and treatment of pulmonary hypertension].

PMID- 20058607
TI  - [Pathogenesis of pulmonary hypertension].

PMID- 20058608
TI  - [Differential diagnosis of pulmonary hypertension].

PMID- 20058609
TI  - [Current treatment of pulmonary arterial hypertension].

PMID- 20058610
TI  - [Future treatment of pulmonary arterial hypertension].

PMID- 20058611
TI  - [Comparison of adenosine versus iloprost by acute vasodilator test in patients of
      pulmonary arterial hypertension complicated with connective tissue diseases].
AB  - OBJECTIVE: To compare the acute hemodynamic effects of adenosine versus iloprost
      in patients of pulmonary arterial hypertension (PAH) complicated with connective
      tissue diseases. METHODS: During right heart catheterization, 18 patients of PAH
      complicated with connective tissue diseases sequentially received intravenous
      infusion of adenosine and inhaled iloprost. After the baseline hemodynamic data
      were obtained, an adenosine infusion was started and titrated to the maximal
      tolerated dose. The hemodynamic parameters were allowed to return to baseline.
      Then inhalation of iloprost was administered. The effects of both medicines on
      the patient's hemodynamics were monitored. RESULTS: As compared with the baseline
      values, the systolic pulmonary artery pressure and pulmonary vascular resistance
      significantly decreased [(71 +/- 30) vs (80 +/- 29) mm Hg and (712 +/- 440) vs
      (824 +/- 464) dyn x s x cm(-5) respectively, both P < 0.05) while the heart rate
      increased significantly [(93 +/- 17) vs (83 +/-16) beat/min, P < 0.05] in the
      adenosine group. Inhaled iloprost could also lower the systolic pulmonary artery
      pressure [(66 +/- 29) vs (79 +/- 28) mm Hg, P < 0.05], mean pulmonary artery
      pressure [(43 +/- 19) vs (52 +/- 19) mm Hg, P < 0.05] and pulmonary vascular
      resistance [(632 +/- 440) vs (816 +/- 448) dyn x s x cm(-5), P < 0.05] without
      any effect upon heart rate. Inhaled iloprost exerted more potent effect on
      lowering mean pulmonary artery pressure and pulmonary vascular resistance than
      adenosine (P < 0.05). The two medicines did not affect cardiac output, pulse
      oxygen saturation or systemic blood pressure. The side effects were fewer in the
      iloprost inhalation group than the adenosine group. CONCLUSION: During acute
      vasodilator testing, inhaled iloprost was more potent than infused adenosine as a
      pulmonary vasodilator in PAH complicated with connective tissue diseases.

PMID- 20058612
TI  - [The acute effects of inhaled iloprost on hemodynamics and oxygenation in chronic
      thromboembolic pulmonary hypertension].
AB  - OBJECTIVE: To evaluate the acute effects of inhaled iloprost on hemodynamics and
      oxygenation in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: A
      prospective study was made. Eighteen patients with CTEPH were enrolled. At right
      heart catheterisation, iloprost was inhaled at 20 microg for 10 - 15 min. Compare
      the value of heart rate (HR), mean blood pressure (mBP), mean pulmonary arterial
      hypertension (mPAP), right atrium pressure (RAP), pulmonary arterial wedge
      pressure (PAWP), cardiac output (CO), pulmonary vascular resistance (PVR),
      systemic vascular resistance (SVR), arterial partial pressure of oxygen (PaO2),
      arterial oxygen saturation (SaO2), mixed venous saturation (SvO2), pulmonary
      shunt fraction (Qs/Qt), alveolar-arterial partial pressure of oxygen [P ( A-a)
      O2] before to after inhaled iloprost in these patients. RESULTS: Significant
      changes (before to after inhalation): mPAP, (53 +/- 11) to (47 +/- 14) mm Hg (P <
      0.01); PVR, (821 +/- 194) to (681 +/- 199) dyn x s x cm(-5) (P < 0.01); RAP, (10
      +/- 6) to (7 +/- 6) mm Hg (P < 0.01). However, HR, PAWP, mBP, CO and SVR had no
      significant changes. At the same time, inhaled iloprost significantly decreased
      PaO2 from (58 +/- 11) to (52 +/- 6) mm Hg (P < 0.01) and increased Qs/Qt from (27
      +/- 11)% to (33 +/- 9)% (P < 0.01)and P(A-a) O2 from (86 +/-39) to (93 +/- 38) mm
      Hg (P < 0.01). CONCLUSION: Inhaled iloprost might instantly improve hemodynamics
      in CTEPH, but at the same time it increased arteriovenous shunts which resulted
      in lower PaO2.

PMID- 20058613
TI  - [Outcome of oral bosentan in children with congenital heart disease associated
      pulmonary arterial hypertension].
AB  - OBJECTIVE: To investigate the outcome of dual endothelin receptor antagonist
      bosentan in children with congenital heart disease (CHD) associated pulmonary
      arterial hypertension (PAH). METHODS: A total of 32 children were recruited into
      this prospective and observational study. Among them, there were 18 cases with
      left-to-right shunt and 14 cases with elevated pulmonary vascular resistance
      (PVR) in functional single ventricle (FSV). All the cases were treated with oral
      bosentan, initiated from 90 days before or 8 years after operation, and were
      followed up periodically to analyze the clinical outcome and monitor its side
      effects. RESULTS: In the left-to-right shunt group, pulmonary arterial pressure
      (PAP) was measured at (57 +/- 26), (52 +/- 31) and (46 +/- 22) mm Hg after oral
      bosentan therapy at 1, 2 and 3 months respectively. The measurements
      significantly decreased as compared with the pre-dosing level of (74 +/- 15) mm
      Hg (P < 0.05). After a 3-months therapy of bosentan, World Health Organization
      functional class (WHO FC) improved significantly (P < 0.01). In the elder cases,
      the 6-minute walking distance after a 3-month bosentan therapy significantly
      increased as compared with the pre-dosing level, i. e. (497 +/- 56) vs (424 +/-
      31) m (P < 0.05). In the FSV group, as compared with the pre-dosing level, the
      transcutaneous oxygen saturation increased significantly in the last follow-up
      during bosentan exposure, i. e. (86 +/- 5)% vs (78 +/- 6)% (P < 0.01). WHO FC
      improved significantly (P < 0.01) and the incidence of facial edema and pleural
      effusion was significant lower (P < 0.05) in the last follow-up for the treatment
      group. Patients tolerated bosentan well and no significant rise in hepatic
      transaminases was observed. CONCLUSIONS: Bosentan is safe in treating CHD
      associated PAH in children. In left-to-right shunt cases, oral bosentan can
      reduce PAP and improve both WHO FC and exercise capacity. And it can also improve
      WHO FC and transcutaneous oxygen saturation in FSV and reduces the occurrence of
      elevated PVR-related complications.

PMID- 20058614
TI  - [Administrating bone marrow mesenchymal stem cells to treat the experimental
      pulmonary arterial hypertension in rats].
AB  - OBJECTIVE: To explore the therapeutic effect and mechanisms of bone marrow
      derived mesenchymal stem cells (MMSCs) transplantation treating pulmonary
      arterial hypertension (PAH) in rats models. METHODS: MMSCs collected from SD rat
      were isolated and cultured in vitro, then Hoechst 33342 staining was performed.
      Eighty healthy male Sprague-Dawley rats were randomly divided into 3 groups:
      pulmonary arterial hypertension group (group H, 30 rats), MMSCs transplanted
      group (group M, 30 rats) and normal control group (group C, 20 rats). The rats in
      groups H and M were given subcutaneous injection of monocrotaline (50 mg/kg)
      respectively to induce the model of PAH. At Day 22 post-induction, the rats in
      group M received sublingual intravenous injection of 1 ml MMSCs at the
      concentration of 5 x 10(6)/ml while the rats in groups H and C were administered
      with equal amount of cell culture medium respectively. General observation was
      made about all groups and survival information were collected after another 4
      weeks. At Day 21, 4 rats from each group were sacrificed. And the rats in all
      groups were sacrificed at Day 49. The survival rate, mean pulmonary artery
      pressure (mPAP) and right ventricle hypertrophy index (RVHI) were determined. The
      microstructural alteration of small pulmonary vessel and immunohistochemistry and
      microvessel density assay of vascular VIII factor-related antigen were performed.
      RESULTS: At the end of the experiment, the survival rates were 50% (15/30) and
      90% (27/30) in groups H and M respectively (P < 0.01). At Day 21, mPAP were (39.1
      +/- 2.5) and (38.5 +/- 2.1) mm Hg in group H and M respectively, and RVHI were
      (34.0 +/- 3.1)% and (33.8 +/- 2.6)% in groups H and M respectively. The
      parameters in both groups were higher than those in group C [(15.2 +/- 1.7) mm Hg
      and (24.7 +/- 2.1)%, both P < 0.01]. At Day 49, mPAP were (42.7 +/- 2.3) and
      (24.7 +/- 2.1) mm Hg in group H and M respectively (P < 0.01), and RVHI were
      (45.1 +/- 3.4)% and (38.8 +/- 3.2)% in group H and group M respectively (P <
      0.01). As compared with group H, the morphological metrological indices of small
      pulmonary arteries significantly improved in group M. The Hoechst 33342 staining
      showed MMSCs were colonized in lungs and differentiated into large number of
      neovascularization, forming plentiful collateral circulations in lung. The
      pulmonary arterial remodeling was reversed in group M. Immunohistochemistry also
      confirmed the finding that a large scale of neovascularization took place in rat
      lungs in group M. Microvessel density in group M [(5.2 +/- 0.8)/HP] was
      significantly higher than that in group H [(1.4 +/- 0.5)/HP, P < 0.01].
      CONCLUSION: MMSC transplantation may reverse pulmonary vascular remodeling
      through differentiation, neovascularization and small pulmonary arterial repair.
      It decreases pulmonary arterial pressure, effectively slows down even reverse
      monocrotaline-induced PAH progression.

PMID- 20058615
TI  - [Randomized clinical study for two types of recombinant human granulocyte colony
      stimulating factor mobilizing peripheral blood and bone marrow stem cells in
      patients receiving allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To compare mobilization kinetics of CD34 + cells and MNC during
      mobilization with either recombinant human granulocyte colony-stimulating factor
      (rHuG-CSF) filgrastim (Huierxue) or topneuter (Teerjin) in allogeneic
      hematopoietic stem cells transplantation (allo-HSCT) donors. METHODS: Two
      different agents of rHuG-CSF, Huierxue (filgrastim) and Teerjin (topneuter), were
      used for hematopoietic stem cells (HSC) mobilization. The HSCs mobilized by each
      agent were compared in mobilization efficacy, quality of stem cells, side effects
      in donors and influence of hematopoietic reconstitution in 52 subjects following
      allo-HSCT. Fifty-two HLA-matched sibling donors, receiving either (rHuG-CSF)
      topneuter (treatment group) or filgrastim (control group), were randomized in
      this study. RESULTS: The peak values of both groups, occurring at both Day 4,
      were (38.9 +/- 3.0) x 10(9)/L and (37.8 +/- 2.9) x 10(9)/L respectively (P >
      0.05). Both agents had the following effects upon the HSC parameters: (4.8 +/-
      0.7) x 10(8)/kg vs (5.1 +/- 0.4) x 10(8)/kg MNC, (1.6 +/- 0.3) x 10(6)/kg vs (1.9
      +/- 0.7) x 10(6)/kg) CD34 + in peripheral blood of donors; (3.8 +/- 0.5)/L vs
      (3.9 +/- 0.7)/L MNC; (1.3 +/- 0.7) x 10(6)/kg vs (1.5 +/- 0.4) x 10(6)/kg CD34 +
      in bone marrow of donors (both P > 0.05). With regards to the effects upon
      hematopoietic reconstitution in subjects following allo-HSCT, both had rapid
      platelet count recovery (14.6 +/- 0.9) vs (15.2 +/-1.6) days (P > 0.05) and
      neutrophil count recovery (18.1 +/- 0.8) vs (17.0 +/- 1.9) days (P > 0.05). The
      adverse events were not significantly different in the HSC donors for these two
      mobilization agents. CONCLUSION: Filgrastim and topneuter demonstrate no
      statistically significant difference in either HSC mobilization kinetics of
      peripheral and bone marrow blood or hematopoietic reconstitution. Topneuter can
      be a reliable agent for donor HSC mobilization and recipient hematopoietic
      reconstitution following allo-HSCT.

PMID- 20058616
TI  - [Phenotypic analysis of Th cells in colon and peripheral blood in patients with
      irritable bowel syndrome].
AB  - OBJECTIVE; To analyze the change of Th1/Th2/Th17 in colonic mucosa and peripheral
      blood in diarrhea-predominant IBS (D-IBS) to uncover the underlying mechanism for
      the activation of mucosal immune system. METHODS: Colonic biopsy specimens and
      peripheral blood were obtained from patients with D-IBS (n = 27) and controls (n
      = 16). Two different groups were classified on the basis of histological
      assessment of biopsy specimens from D-IBS patients. One group (14 of 27) had
      normal conventional histology (IBS), while another group (13 of 27) had
      nonspecific microscopic inflammation (IBS-A). Flow cytometric detection of
      intracellular IFN-gamma/IL-4/IL-17 cytokine production was employed to
      investigate Th1, Th2 and Th17 cells in colonic lamina propria and peripheral
      blood. Western blot was used to determine the expressions of IL-12, IL-4 and IL
      17 in colonic mucosa. The levels of IL-12, IL-4 and IL-17 in peripheral blood
      were detected by ELISA. RESULTS: In colonic mucosa, the proportion of Th17
      increased in IBS-A group as compared with controls [3.60 (4.05) vs 1.25 (3.70), P
      = 0.045], but not in IBS group. No difference could be observed in the
      frequencies of Th1 and Th2 in colonic mucosa and peripheral blood. The levels of
      IL-12, IL4 and IL-17 in IBS and IBS-A showed no difference in either colonic
      mucosa or peripheral blood. CONCLUSION: Subgroup of D-IBS showed abnormal
      conventional histology, implicating the activation of mucosal immune system in
      pathogenesis. The shift of Th1/Th2/Th17 balance in colonic mucosa showed the
      enhanced Th17 activity.

PMID- 20058617
TI  - [Expression of CD40 in human gastric cancer tissue and its prognostic
      correlation].
AB  - OBJECTIVE; To investigate the expression of CD40 in gastric cancer and explore
      the correlation of CD40 with the outcome of patients. METHODS: The expression of
      CD40 was examined by immunohistochemistry in human gastric cancer tissues (73
      cases) and adjacent normal gastric tissues (51 cases). CD40 mRNA was detected by
      RT-PCR in 11 gastric cancer and 11 adjacent normal gastric tissues. The patients
      were followed up for 60 months. The correlation of CD40 expression and the
      overall survival time were evaluated by Kaplan-Meier chart and Log-Rank test. Cox
      model was used for multivariate analysis. RESULTS: The immunoreactivity of CD40
      increased in 35/73 gastric cancer tissues (47.9%) as compared to the tumor-free
      tissues (P = 0.0063). CD40 mRNA were detected in 72.7% (8/11) gastric cancer
      tissues, while not in all tumor-free tissues. After a 5-year follow-up, the
      survival rate was 57.9% (22/38) in CD40-negative patients, and 5.7% (2/35) in
      CD40-positive patients (P = 0.0022). The median survival time of patients with
      negative, positive, and strong CD40 expression was 56, 29 and 11 months
      respectively (P = 0.0085). Cox regression analysis suggested that CD40, lymph
      node metastasis and TNM stage were independent factors affecting the prognosis of
      gastric cancer patients. CONCLUSION: Normal and malignant gastric tissues are
      found to have its own unique CD40 expression patterns. CD40 may play a role in
      metastatic spread of gastric cancer and its expression may be used as an
      important survival predictor in human gastric cancer.

PMID- 20058618
TI  - [Serum levels of retinol-binding protein-4 and its association with metabolic
      syndrome in first-degree relatives of type 2 diabetes mellitus].
AB  - OBJECTIVE: To evaluate serum levels of retinol-binding protein-4 (RBP-4) in first
      degree relatives (FDR) of type 2 diabetes mellitus (T2DM) with different glucose
      tolerance status and to observe its correlation to metabolic syndrome (MS).
      METHODS: Subjects from FDR of T2DM, including 174 with NGT, 55 with IGT/IFG, and
      71 patients with newly diagnosed of T2DM and 114 subjects without diabetic family
      history as control group [(18 +/- 7) microg/ml vs (22 +/- 8) microg/ml, (NC) [(18
      +/- 7) microg/ml vs (22 +/- 8) microg/ml, were recruited. Serum RBP-4 level was
      measured by radioimmunoassay. Insulin resistance was evaluated by the homeostasis
      model assessment (HOMA-IR). MS was diagnosed according to 2005 IDF consensus.
      RESULTS: (1) Serum RBP-4 levels in NC, NGT, IFG/IGT and T2DM groups were (18 +/-
      7), (22 +/- 8), (24 +/- 9) and (26 +/- 9) microg/ml respectively. Serum RBP-4 was
      significantly elevated in NGT group of diabetic FDR as compared with NC group
      [(26 +/- 9) microg/ml vs (24 +/- 9) microg/ml], and increased with the severity
      of glucose intolerance. However, no difference was found between serum RBP-4 in
      the IFG/IGT and T2DM groups. (2) When the distribution of RBP-4 was stratified
      into quartiles (Q1-Q4), subjects in the top quartile (Q4) was not only associated
      with greater risk for impaired glucose regulation as compared with Q1 OR = 5.26)
      , but also significantly with risk for hypertension (OR = 1.96), dyslipidemia (OR
      = 4.14), obesity (OR = 2.18) and MS (OR = 4.30). CONCLUSION: (1) Serum RBP-4
      levels in FDR of T2DM were elevated significantly even before the development of
      impaired glucose regulation and were further increased with severity of glucose
      tolerance, suggesting a possible role of RBP-4 in the early pathogenesis of T2DM.
      (2) Serum RBP-4 level was closely related to MS.

PMID- 20058619
TI  - [Primary preventive effect of metformin upon atherosclerosis in patients with
      type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the preventive action of metformin for atherosclerosis
      (AS) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 140
      cases with T2DM were assigned to 2 groups taking metformin (n = 75) or not (n =
      65). All cases received intensive control of blood glucose, blood pressure and
      blood lipids for 100 weeks. The data before and after intensive control were
      recorded and statistically analyzed. Common carotid intima-media thickness (CC
      IMT) was the efficacy endpoint of AS. RESULTS: Diastolic blood pressure (DBP),
      fasting blood glucose, post 2-hour blood glucose, glycated hemoglobin A1c,
      triglyceride (TG) and total cholesterol (TC) decreased in both groups after
      intensive metabolic control for 100 weeks (P < 0.05). Body mass index (BMI), HOMA
      insulin resistance index (HOMA-IR) and CC-IMT decreased in metformin group (P <
      0.05) while high-density lipoprotein cholesterol (HDL-C) increased (P < 0.05).
      BMI (23.1 +/- 0.98) kg/m2, HOMA-IR (1.68 +/- 0.20) and CC-IMT (0.55 +/- 0.13) mm
      in metformin group were lower than those in non-metformin group [(24.1 +/- 0.05)
      kg/m2, 2.03 +/- 1.38, (0.70 +/- 0.15) mm)] at 100 week (P < 0.05). CC-IMT was
      positively correlated with BMI (r = 0.489, P < 0.05) , TC (r = 0.429, P < 0.05),
      low-density lipoprotein cholesterol (LDL-C) (r = 0.426, P < 0.05) and HOMA-IR (r
      = 0.428, P < 0.05). CONCLUSION: Metformin attenuates CC-IMT of patients with T2DM
      and it has the primary preventive effect upon AS in patients with T2DM.

PMID- 20058620
TI  - [Diagnosis and treatment of primary pigmented nodular adrenocortical disease
      report of 4 cases].
AB  - OBJECTIVE: To study the diagnosis and treatment of primary pigmented nodular
      adrenocortical disease (PPNAD). METHODS: The clinical data including symptom,
      endocrinal examination, surgical operation and prognosis of 4 cases of PPNAD
      hospitalized from 2000 to 2007 were analyzed respectively, relative literature
      were reviewed. RESULTS: 1 case received total adrenalectomy needed adrenocortical
      hormone postoperatively, 3 cases responded favorably to subtotal adrenalectomy
      and did not need adrenocortical hormone, however, 1 case was diagnosed of thyroid
      carcinoma 2 years after subtotal adrenalectomy. CONCLUSIONS: PPNAD is a rare
      subtype of ACTH-independent Cushing's syndrome, the diagnosis is depend on
      symptom, endocrinal examination and pathology. Total adrenalectomy is suitable to
      the patients with obvious symptom; subtotal adrenalectomy to the patients with
      mild symptom, the lesion of other endocrinal organ must be followed up
      postoperatively.

PMID- 20058621
TI  - [Diagnosis of testicular cancer: review of 47 cases].
AB  - OBJECTIVE: To improve the diagnostic level of testicular cancer by a
      retrospective review of 47 cases. METHODS: The symptoms, signs, imaging studies,
      tumour markers and histological diagnoses of 47 cases were reviewed. RESULTS: The
      mass in testes was palpated in all patients. As a useful tool in the diagnosis of
      testicular cancer, scrotal ultrasonography had a detecting sensitivity over 90%.
      Though sensitive to retroperitoneal lymph nodes, CT had a certain level of false
      positive rate. Tumor markers, especially AFP, were significantly useful in the
      diagnosis and prognosis of testicular cancer. Histological examination showed 27
      cases of seminoma, 7 cases of embryonal carcinoma, 6 cases of teratoma, 3 cases
      of lymphoma, 1 case of spermatocytic seminoma and 1 case of sarcoma. CONCLUSION:
      Patient self-examination is extremely helpful for an earlier diagnosis.
      Ultrasonography and CT are invaluable in the diagnosis and staging of testicular
      cancer. Playing key roles in the diagnosis and prognosis of testicular cancer,
      tumour markers should be routinely examined.

PMID- 20058623
TI  - Splitting time from space.

PMID- 20058622
TI  - [Effects of ShenSongYangXin on action potential and some current channels in
      isolated rabbit pulmonary vein cardiomyocytes].
AB  - OBJECTIVE: To investigate the effects of ShenSongYangXin on action potential and
      some current channels in isolated rabbit pulmonary vein cardiomyocytes and to
      elucidate its possible mechanism of curing atrial fibrillation. METHODS: Action
      potentials as well as L-type calcium channel current (I(Ca-L)), transient outward
      potassium current (I(K1)) and inward rectifier potassium current (I(To)) were
      recorded using whole cell patch-clamp technique. RESULTS: ShenSongYangXin
      prolonged the action potential duration (APD) significantly, APD90 was enlarged
      from (187 +/- 49) ms to (286 +/- 76) ms at the concentration of 5 mg/ml and to
      (312 +/- 82) ms at the concentration of 10 mg/dl respectively (P < 0.05). It also
      depressed the current of I(Ca-L), I(K1) and Iro in a concentration-dependent
      manner. CONCLUSION: ShenSongYangXin can be used to treat atrial fibrillation
      through its actions on multiple current channels.

PMID- 20058624
TI  - Extreme monotremes.

PMID- 20058625
TI  - Tinier tyrannosaurs.

PMID- 20058626
TI  - Inflammatory clues.

PMID- 20058628
TI  - Piercing the plasma.

PMID- 20058629
TI  - The shape of atoms.

PMID- 20058627
TI  - Conditional consciousness.

PMID- 20058630
TI  - Setting boundaries.

PMID- 20058631
TI  - Zoning for oceans.

PMID- 20058632
TI  - Transgressing planetary boundaries.

PMID- 20058633
TI  - Political science.

PMID- 20058634
TI  - War is peace.

PMID- 20058636
TI  - The no-money-down solar plan.

PMID- 20058635
TI  - Portrait of a black hole.

PMID- 20058637
TI  - Delivering the U.S. from oil.

PMID- 20058638
TI  - Ocean overhaul.

PMID- 20058639
TI  - The omnipotence machines.

PMID- 20058640
TI  - Know if disease grows inside you.

PMID- 20058641
TI  - Expanding the limits of life.

PMID- 20058642
TI  - Methane: a menace surfaces.

PMID- 20058643
TI  - Decoding an ancient computer.

PMID- 20058644
TI  - The double life of ATP.

PMID- 20058645
TI  - Illuminating the lilliputian.

PMID- 20058646
TI  - MDT's five-minute interview.

PMID- 20058647
TI  - Live cells and cytotoxicity assessment.
AB  - Problems with the use of conventional cytotoxicity tests to evaluate biological
      risk with biomaterials are leading to the development of alternative procedures
      based on cell function. These tests, recently discussed at a conference in China,
      provide an attractive option for the future.

PMID- 20058648
TI  - Managing risk for silicone tubing applications.
AB  - Quality must be designed into medical devices, including into their raw materials
      and components. Operating according to the critical principles of medical device
      good manufacturing practices ensures that the silicone tubing incorporated into
      devices has the highest standards of quality and safety.

PMID- 20058649
TI  - Closed-loop micropumps.
AB  - The small size, low power consumption and attractive price of micropumps make
      them ideal for use in medical delivery systems. This article discusses two
      designs of closed-loop controlled micropumps that can be employed to meet
      differing levels of accuracy and portability.

PMID- 20058650
TI  - Clinical studies in Italy.
AB  - The requirements for conducting medical device clinical studies in Europe are not
      identical in all Member States. That is, variations exist in the way that the
      requirements in the European Directives are interpreted and enforced. This
      article provides an overview of the requirements that currently apply in Italy.

PMID- 20058651
TI  - Isolating USB connections in medical equipment.
AB  - Although offering several benefits, the universal serial bus (USB) port has not
      been rapidly adopted for connecting medical equipment. This is because it could
      affect safety procedures, with equipment not operating isolated from the mains.
      To overcome this, a single package isolation device has been developed that can
      be inserted directly into the USB signal path.

PMID- 20058652
TI  - Supply chain quality.
AB  - As the development of complex manufacturing models and virtual companies become
      more prevalent in today's growing global markets, it is increasingly important to
      support the relationships between manufacturer and supplier. Utilising these
      relationships will ensure that supply chains operate more effectively and reduce
      costs, risks and time-to-market time frames, whilst maintaining product quality.

PMID- 20058653
TI  - Needles: a comparison study.
AB  - For patients with a chronic condition such as multiple sclerosis (MS) who self
      administer injectable therapies, comfort is important. This article reports on a
      comparison study of needles used to administer MS therapies and calls for medical
      device manufacturers to develop needles with decreased penetration forces to
      minimise trauma, which may increase patient comfort.

PMID- 20058654
TI  - Advantages of flexible assembly automation systems.

PMID- 20058655
TI  - Ireland medical technology industry.

PMID- 20058656
TI  - [Application in veterinary and human clinical toxicology].

PMID- 20058657
TI  - [Toxicology in the network society: focus on suicide attempts. Editorial].

PMID- 20058658
TI  - [Light and shadow of the internet society from the viewpoint of poison
      information service].

PMID- 20058659
TI  - [The internet and acute poisoning].

PMID- 20058660
TI  - [Hydrogen sulfide poisoning and the internet].

PMID- 20058661
TI  - [Effects of mass media on imitative suicides by readily available toxic
      substances].

PMID- 20058662
TI  - [On the internet and suicide].

PMID- 20058663
TI  - [Simple detection methods for determination of poisons].

PMID- 20058664
TI  - [Kyorin University Hospital, Trauma & Critical Center, Poison Analytical
      Laboratory].

PMID- 20058665
TI  - [Kansai Medical University (Department of Clinical Sciences and Laboratory
      Medicine)].

PMID- 20058666
TI  - [Investigation of acute poisoning in small animals based on JPIC inquiries].

PMID- 20058667
TI  - [Anatomical structure related to eyelid surgery].

PMID- 20058668
TI  - [Magnetic resonance imaging findings on the eyelids of Japanese cadavers for
      anatomical studies and a comparative examination of their histological pictures].
AB  - OBJECTIVE: To clarify ambiguous areas in interpreting MR images of Japanese
      eyelids, a histological examination was conducted on cadavers after the MRI for a
      comparative evaluation. SUBJECTS AND METHODS: Orbital sections including the
      unilateral upper and lower palpebrae of two Japanese cadavers (an 87-year-old
      woman and a 49-year-old man) were examined. Following MRI, the specimens of the
      same cadavers were examined histologically for a comparative evaluation. RESULTS:
      In both cadavers, a high signal intensity area with a hazy appearance unlike the
      orbital fat--fibroadipose tissue rich with connective tissue--was recognized
      between the orbicularis muscle and orbital septum. The same high signal intensity
      area that appeared to encase the posterior section of the descending orbital fat
      was also composed of fibroadipose tissue. Because of the presence of this
      intervening fibroadipose tissue, the posterior surface of the orbicularis muscle
      and the orbital septum could not come into contact with each other. CONCLUSION:
      Although limited to only two subjects, the current observation proved that
      fibroadipose tissue exists not only in the superficial layer of the orbital fat
      but that it further descends to surround the lowest portion of the orbital fat.
      As already reported, it was mainly the fibroadipose tissue, but not the orbital
      fat, that descends into the palpebral space.

PMID- 20058669
TI  - [Examination of the optic nerve head blood flow in patients with proliferative
      diabetic retinopathy treated with vitrectomy].
AB  - PURPOSE: To evaluate the optic nerve head blood flow level of a patient with
      proliferative diabetic retinopathy before and after vitrectomy, using laser
      speckle flow graphy (LSGF) for noninvasively ocular blood flow analysis. METHODS:
      Twenty three eyes of 23 patients were recruited in the present study who
      underwent vitrectomy at Sapporo Medical University hospital. We measured optic
      nerve head blood flow before and 2 weeks after operation. The average blood
      pressure and ocular perfusion pressure were measured before and after surgery.
      RESULTS: Blood flow in the central retinal artery and on both the nasal and
      temporal sides of the optic nerve head significantly increased after surgery in
      all cases. In cases where the post-operative blood flow in the optic disk
      temporal side increased by more than 59%, visual acuity was also ameliorated.
      CONCLUSION: LSFG is an effective method for evaluating the optic nerve head blood
      flow noninvasively, and may be useful for prediction of postoperative visual
      acuity prognosis.

PMID- 20058670
TI  - [Time course of changes in contrast sensitivity function after application of
      antiglaucomatous eyedrops].
AB  - PURPOSE: Some antiglaucomatous eyedrops can cause blurred vision after
      application. Contrast sensitivity after application, however, has not been
      examined. The purpose of this study was to investigate the influence of
      antiglaucomatous eyedrops on contrast sensitivity function. METHODS: In 23 eyes
      of 23 normal volunteers (34.9 +/- 14.5 years [mean +/- SD]), contrast sensitivity
      was measured before and 2, 5, 10, and 15 minutes after application of
      antiglaucomatous eyedrops. Three drugs, timolol maleate ion-activated gel,
      timolol maleate thermosetting gel, and brinzolamide were tested in this study,
      and the time course of changes in contrast sensitivity after instillation was
      statistically analyzed and compared between the drugs. RESULTS: All drugs
      significantly reduced contrast sensitivity function (p<0.001). The reduction in
      contrast sensitivity persisted for approximately 5 minutes after instillation of
      timolol maleate ion-activated gel and brinzolamide. For timolol maleate
      thermosetting gel, the reduction in contrast sensitivity lasted for about 10
      minutes, but the reduction immediately (two minutes) after instillation was
      significantly smaller than that of the other two drugs (p<0.05). CONCLUSIONS:
      Instillation of these three drugs temporarily degrades contrast sensitivity
      function, leading to blurred vision, which should be sufficiently explained to
      patients before treatment with these eyedrops.

PMID- 20058671
TI  - [Amblyogenic factors in patients with an early-onset type of developmental
      glaucoma].
AB  - PURPOSE: To extract amblyogenic factors in eyes with an early-onset type of
      developmental glaucoma despite good post-operative intraocular pressure (IOP)
      control. MATERIALS AND METHODS: Subjects were 24 eyes of 14 patients that
      underwent successful trabeculotomy by 3 years of age and had their best-corrected
      visual acuity (BCVA) development monitored for at least 5 years or more after
      surgery. Principal factor analysis was performed on final logarithmic BCVA, age
      at operation, corneal diameter, corneal opacity, Haab's striae, spherical
      equivalent of final refractive error, final astigmatic degree, axial length,
      preoperative IOP, final vertical cup per disc ratio, and either presence or
      absence of eccentric fixation. Latent variables that had an eigenvalue of 1 or
      more underwent an orthogonal rotation with the varimax method in order to yield
      factor loadings of these 11 parameters. RESULTS: The parameters that had absolute
      factor loading values of 0.6 or more in a latent variable including final BCVA
      were final BCVA, fixation status, refractive error, and Haab's striae. Two
      variable comparisons also supported the significant association of the latter
      three parameters with final BCVA. CONCLUSIONS: Amblyogenic factors in eyes with
      an early-onset type of developmental glaucoma were eccentric fixation, myopic
      refractive error, and the presence of Haab's striae.

PMID- 20058672
TI  - [RNA world/pseudogene/non-coding RNA].

PMID- 20058673
TI  - [Characteristics of the left and right scanning in schizophrenia patients using
      exploratory eye movements: comparison with healthy subjects].

PMID- 20058674
TI  - [Alcohol-related disorders and suicide].
AB  - Since 1998, more than 30,000 people have committed suicide each year, and suicide
      has become one of the most serious social problems in Japan. It is well
      established that both acute and chronic alcohol intake are associated with
      suicidal behavior. However, the relationship between alcohol consumption and
      suicide has received less attention than that of depression in Japan. We showed
      the following: 1) Many suicide cases were heavy drinkers. 2) A positive
      correlation exists between per capita alcohol intake and the suicide rate. 3)
      Heavy drinking is a risk factor for suicide. Consequently, we reviewed the
      literature concerning the association between alcohol dependence and suicide.

PMID- 20058675
TI  - [A case of depression whose symptoms cured by setting her psychological base on
      the transcendent level].
AB  - We report the case of a female in her 40s diagnosed with depression. She was
      raised by an eccentric father, suspected of having pervasive developmental
      disorder, and a dominant mother. After graduating from high school, she worked as
      a clerk in a company for twenty years or so; however, a change in her work
      environment made her fall into a depressive state. Her worsening depression
      caused her impulsive resignation and disappearance for about four months. She
      spent the duration of her disappearance traveling the country, with no
      dissociative episodes. After returning, she received treatment for depression as
      an inpatient for about four months. During the first month of hospitalization,
      she mainly complained of a depressive mood and anxiety over the prognosis of her
      disorder, while she made scarcely any progress in introspection. In the second
      month, she gradually advanced with introspective work, but, as her introspection
      progressed, her depressive mood became aggravated. The therapist avoided
      intervention to modify her cognition, and told her the following: "it is better
      not to persist in managing your depressive mood itself because curing depression
      does not mean resolving the superficial depressive mood, but to achieve a
      condition not directly influenced by mood." Then, at the beginning of the third
      month, she became aware of "the presence of God" and, at the same time, her
      depressive mood greatly improved. She extended her sympathy to her mother with
      her unfortunate life history, and expected her mother to change as she herself
      had experienced, but, disappointed by her mother, she experienced anxiety attacks
      and came to realize her own internal rage against significant persons in her life
      including her mother. After "the Great being" experience, she, who had formerly
      attended Christian church for a short time, started to read the Bible, but she
      still hesitated about committing herself to "religious following." One day during
      the last month of hospitalization, as she prayed to God for healing when she read
      a part in the Bible about a woman suffering from a hemorrhage for twelve years
      who touched the hem of Jesus' garment and was healed immediately (Matthew 9:20-22
      and Luke 8:43-48), the patient suddenly experienced "the salvation of God" and
      realized what trust really meant. Through the experience, her clinical problems
      became totally cured, and the therapy concluded with her discharge from hospital.
      Several months later, she sent the therapist a letter including the following
      message: "I am grateful to the Lord for salvation from anxiety and irritation,
      but to the therapist for helping me realize it." This clinical course can be
      understood based on the patient's clinical problems (e.g., despair, anxiety, and
      depression), arising from the breakdown of her efforts to maintain stability by
      founding her psychological base on her feelings of omnipotence, avoiding facing
      her internal negative psychological factors (e.g., rage), and these were
      automatically resolved when her psychological base was switched to the
      transcendent level through "the Great being" experience and "the salvation of
      God." Such a sudden, marked improvement resembles what Miller and C'de Baca
      reported as "quantum change," of which the characteristics are vividness,
      surprise, benevolence, and permanence. The therapist paid attention to maintain a
      constant psychological distance from the patient, not persisting in modifying her
      cognition, with the transcendent level being the basis for the entire therapy.
      This stance of the therapist itself was considered to prompt her transcendence
      and bring about her eventual cure. This clinical course seemed to be highly
      suggestive of a psychotherapeutic mechanism, indicating the close relationship
      between the transcendent level and basic trust.

PMID- 20058677
TI  - Postgraduate training program of National Center of Mental Health, Mongolia.

PMID- 20058678
TI  - Postgraduate psychiatric training in Thailand.
AB  - In Thailand, after medical students graduated from medical schools, the general
      practitioners have to work for the government for at least three years. Then,
      they can enroll in postgraduate training program. Postgraduate training usually
      takes three to four years. All of the psychiatric training programs are
      supervised and monitored by the board of education of the Royal College of
      Psychiatrists of Thailand (RCPsychT). One of the missions of all training
      institutes is to prepare residents to be the high qualified psychiatrists to
      serve the mental well-being of Thai people. Additionally, they should teach the
      learners to be the leaders in academic and research fields in psychiatry.
      Currently, there are nine psychiatric training institutions in Thailand, most of
      which are running by university programs. The training program core curriculum
      composes of the compulsory rotations such as general psychiatry, child and
      adolescent psychiatry, neurology, consultation-liaison psychiatry, mental
      hospital psychiatry and addiction psychiatry. Moreover, the residents also have
      three months for elective in each program. The learning process includes
      practicing in an out-patient and in-patient unit under psychiatric staff
      supervision, individual and group supervision, case conference, journal club,
      book club and grand round etc. Research in field of psychiatry and social
      sciences is also compulsory for board examination. The RCPsychT approved two
      Certificate Diplomas including Diploma of Thai Board of Psychiatry, and Diploma
      of Thai Board of Child and Adolescent Psychiatry. There are only nine psychiatric
      training institutes and only thirty to forty residents enrolled in these programs
      in each year. The compact and collaboration of all training institutes bring
      about the benefits in efficiency programs management by regular meeting of
      representatives from each institute. They keep the standard of training program
      to progress in the same vision and direction. Furthermore, residents of each
      training programs can exchange and request for elective rotation at the other
      institutes.

PMID- 20058679
TI  - Postgraduate psychiatric training in Singapore.

PMID- 20058680
TI  - [The preventive effect of 23-valent pneumococcal polysaccharide vaccine against
      drug-resistant Streptococcus pneumonia in patients with chronic respiratory
      disease].
AB  - OBJECTIVE: To elucidate the preventive effect of 23-valent pneumococcal
      polysaccharide vaccine (PV) on drug-resistant Streptococcus pneumoniae.
      METHODOLOGY: Participants (outpatients, over 60 years of age, and with chronic
      lung disease) were interviewed and divided into two groups: the PV-vaccinated
      group (n=722) and the non-vaccinated group (n=872). The antimicrobial
      susceptibility and the genotype of antibiotic-resistant genes among the isolated
      pneumococcal strains from sputum before and after vaccination were studied.
      RESULTS: The number of the isolated strains was as follows: prior to the
      vaccination, 24 isolates in the vaccinated group, 18 isolates in the non
      vaccinated group; after vaccination (within 5 years), 53 isolates in the
      vaccinated group, 46 isolated in the non-vaccinated group. The PV decreased the
      frequency of Penicillin G-resistant strains successfully (from 16.7 to 7.5%) in
      the vaccinated group while the frequency increased (from 5.5 to 15.2%) in the non
      vaccinated group during the same period. In genetic analysis, the rates of
      strains with altered pbpla, pbp2x and pbp2b were decreased in the vaccinated
      group than the non-vaccinated group (28.6% versus 53.3%). CONCLUSIONS: The 23
      valent pneumococcal polysaccharide vaccine may have a preventive effect against
      drug-resistant Streptococcus pneumoniae.

PMID- 20058681
TI  - [Evaluation of COBAS TaqMan: a real-time PCR-based diagnostic kit for
      mycobacteria].
AB  - The real-time PCR-based diagnostic kits, COBAS TaqMan MTB and COBAS TaqMan MAI
      (Roche Diagnostics, Tokyo, Japan), were developed to detect Mycobacterium
      tuberculosis (MTB) and M. avium (MAV)/M. intracellulare (MIN), respectively. The
      TaqMan kits simultaneously perform amplification and detection of mycobacterial
      DNA to reduce assay time. We evaluated the diagnostic accuracy of both TaqMan
      kits in 781 clinical specimens, and compared the results with those obtained from
      the AMPLICOR MTB and MAI kits. With smear-positive specimens, the TaqMan kits
      showed 100% concordance with AMPLICOR in MTB, MAV and MIN. With all specimens,
      the concordances of TaqMan with AMPLICOR were 99.1%, 99.0%, and 99.7% in MTB, MAV
      and MIN, respectively. Four specimens for MTB and one for MAV were AMPLICOR
      positive/TaqMan negative. Among them, two specimens were culture-positive for MTB
      and one for MAV. Three specimens for MTB, seven for MAV, and two for MIN were
      AMPLICOR negative/TaqMan positive. Among them, two specimens were culture
      positive for MTB, seven for MAV, and one for MIN. In twelve out of 21 specimens
      in which AMPLICOR failed to activate PCR, TaqMan successfully determined the
      results which were in concordance with those of mycobacterial culture. Thus, our
      data suggest that the accuracy of TaqMan in detecting mycobacterial DNA is
      superior to that of AMPLICOR. We conclude that TaqMan, which is an easy and rapid
      DNA amplification test, is useful for detecting MTB, MAV and MIN.

PMID- 20058682
TI  - [Efficacy of fluoro-2-deoxyglucose positron emission tomography imaging in
      response evaluation of patients with small cell lung cancer (pilot study)].
AB  - The purpose of this study was to assess the feasibility of PET/CT in response
      evaluation of patients with small cell lung cancer (SCLC). Among the 25 patients
      with primary small cell lung cancer who had been treated from August 2004 through
      to May 2008, we compared the response evaluation between conventional CT and
      fluoro-2-deoxyglucose positron emission tomography (FDG-PET), [CMR (Complete
      Metabolic Response), PMR (Partial Metabolic Response), SMD (Stable Metabolic
      Disease), PMD (Progressive Metabolic Disease)] before and after the treatment.
      Response assessment was discordant in 2 out of 25 cases (8%) after the first
      cycle of chemotherapy and in 3 out of 19 cases (16%) after the fourth cycle of
      chemotherapy. Two discordant cases after the first cycle of chemotherapy were PR
      and SD respectively by CT but both were found to be PMD by PET. Two out of three
      discordant cases after the fourth cycle of chemotherapy were PR by CT but both
      found to be CMR by PET. These results suggest that FDG-PET is useful for response
      assessment of early diagnosis of recurrence and prognostic outlook in small cell
      lung cancer, however further cases need to be collected.

PMID- 20058683
TI  - [A case of early-onset cyclophosphamide-induced pneumonitis diagnosed by
      rechallenge test].
AB  - A 59-year-old woman began to complain of cough, dyspnea, and fever 2 weeks after
      3 courses of chemotherapy with cyclophosphamide (800 mg) and adriamycin (80 mg)
      for breast cancer. Chest radiography showed diffuse ground-glass shadows in the
      central areas of bilateral lung fields. Chest CT also showed diffuse ground-glass
      opacities in the central areas of bilateral lung fields. Arterial blood gas
      analysis revealed mild hypoxia. A lymphocyte stimulation test with peripheral
      blood lymphocytes for cyclophosphamide was negative. A mild increase of
      lymphocytes was observed in the cell population of bronchoalveolar lavage fluids
      and no microorganisms were detected. Her respiratory condition improved after
      glucocorticoid therapy. A rechallenge test with cyclophosphamide was performed
      after obtaining informed consent. There was no significant change in symptoms or
      chest radiography results 24 hours after intravenous administration of
      cyclophosphamide (100 mg). However, a transient decrease of PaO2 with peripheral
      eosinophilia was observed. Thus, a diagnosis of early-onset cyclophosphamide
      induced pneumonitis was established.

PMID- 20058684
TI  - [A case of neurosarcoidosis discovered in a patient complaining of chest pain].
AB  - A 60-year-old woman complained of chest and axillary pain, which had initially
      appeared three months previously and had recently become worse. A chest CT
      revealed hilus-mediastinal lymphadenopathy. Because an increased serum ACE level
      was observed, sarcoidosis was suspected and further investigations performed. The
      number of lymphocytes had also increased in the BALF (67%) and the CD4/CD8 ratio
      was significantly higher than normal (7.5). A histological examination of a
      specimen obtained by TBLB revealed epithelioid cell granuloma. FDG-PET CT showed
      an increased uptake in the hilus-mediastinal lymph node and thoracic spinal cord.
      An abnormal image suggesting extradural epithelioid cell granuloma was identified
      at the C7-Th8 levels of the thoracic spinal cord by MRI. The pain was thus
      suspected to have been caused by compression of the spinal cord due to the
      presence of the epithelioid cell granuloma. Oral administration of prednisolone
      (50mg/day) improved her symptoms as well as the findings on both FDG-PET CT and
      MRI.

PMID- 20058685
TI  - [A case of bronchogenic carcinoma which obtained long-term relapse free survival
      by argon plasma coagulation].
AB  - A 69-year-old man was admitted complaining of bloody sputum. A chest X-ray and CT
      revealed no abnormal findings, but bronchoscopy revealed a squamous cell
      carcinoma nodular lesion in the bifurcation between the left B(1+2)a and B(1+2)b.
      After two courses of chemotherapy (CBDCA + PAC), the nodular lesion disappeared.
      Another nodular squamous cell carcinoma grew in the orifice of the left B(1+2)
      nine months later, but this time chemotherapy was ineffective. The nodular tumor
      was cauterized twice with argon plasma coagulation, and no recurrence appeared
      for twenty-six months.

PMID- 20058686
TI  - [Three cases of removal of intrabronchial metal nails].
AB  - We describe the successful extraction from an airway of foreign bodies metal
      nails in three cases. They were all carpenters, and often held nails between
      their lips. Case 1: a 72-year-old man had aspirated a nail three months earlier,
      but did not seek medical assistance at the time. A chest X-ray film and CT
      examination revealed a nail in the peripheral S7 region of the right lower lobe.
      The nail could not be extracted with forceps via bronchoscopy, so video-assisted
      thoracic surgery was performed. During surgery, the nail moved to the truncus
      intermedius, then it was extracted using bronchoscopy forceps. The extracted nail
      was rust-proof, and no rust was observed. Case 2 : a 76-year-old man visited our
      hospital with a history bloody sputum with a slightly dry cough for two months. A
      chest X-ray film showed a nail in the right hilum. Bronchoscopy revealed the nail
      covered with mucinous secretion in the right B7, and it was extracted by forceps.
      It was a rust-proof type nail, and no granulation tissue was observed in the
      bronchus. Case 3: a 74-year-old man visited our hospital because of dry cough for
      two months. A chest X-ray revealed a nail in the right hilus and bronchoscopy
      showed the nail was buried in reactive granulation tissue in the right middle
      lobe bronchus and could not be observed from the surface. Tranilast (n-[3,4
      dimethoxycinnamoyl] anthranilic acid) at 300 mg/day and Methylprednisolone at 250
      mg/day were prescribed for 4 days, followed by a reduction of the corticosteroid
      to 40 mg/day for 3 days. Seven days later, the granulation tissue and mucosal
      edema had diminished, and the nail was successfully extracted. The extracted nail
      was not rust-proof and had swollen with rust. These nails were found a few months
      after aspiration. The reason why these were not defected was possibly that the
      long and narrow shape did not obstruct the segmental bronchus and the symptoms
      can be less severe compared with other foreign bodies. The rust-proof nails were
      covered with mucinous secretion, but the nail without coating had rusted and
      caused reactive granulation tissue and swelling observed. Corticosteroid and
      Tranilast are thought to be effective in reducing such granulation tissue in
      airways.

PMID- 20058687
TI  - [A case of transcatheter coil embolization for pulmonary arteriovenous
      malformation complicated with hepatic arteriovenous malformation].
AB  - A 57-year-old woman in whom pulmonary arteriovenous malformation (PAVM)
      associated with hereditary hemorrhagic telangiectasia (HHT) had been diagnosed
      after a chest X-ray film showed an abnormal shadow at the age of 39. After
      diagnosis, she suffered two ischemic brain attacks, presumably caused by PAVM.
      She was admitted to our hospital for evaluation and treatment of PAVM on February
      9, 2008. We confirmed two PAVMs in right S(3)a and left S(9)a by chest CT scan
      and angiography. In addition, abdominal CT revealed hepatic arteriovenous
      malformation (HAVM). HAVM were thought to increase venous return to the right
      heart, (which might cause pulmonary hypertension after the embolization of
      PAVMs), leading to right heart failure. In order to prevent neurological events
      in future, we performed an embolization of PAVM with individual coils at monthly
      intervals. Six months after the last embolization treatment, she showed no
      symptoms of right heart failure and the size of PAVMs decreased. It is considered
      important for a patient with PAVM associated with HHT to undergo a thorough
      examination for arteriovenous malformation in other organs, before coil
      embolization.

PMID- 20058688
TI  - [A case of Wegener's granulomatosis].
AB  - A 73-year-old man who had been diagnosed with bronchiectasis in 2002 was admitted
      to our hospital with hemoptysis in March 2003. Upon detecting P. aeruginosa from
      his sputum culture, we diagnosed his condition as an exacerbation of a chronic
      respiratory infection with bronchiectasis. Levofloxacin was effective and his
      infection condition was resolved. In June 2006 he was admitted to our hospital
      again with hemoptysis and complaining of fever. This time, Levofloxacin was not
      effective. After admission, fourth-generation cephem, carbapenem, and new
      quinolone antibiotics were ineffective. However, micafungin sodium seemed to
      combat the infection. The patient was negative for PR-3 ANCA in laboratory
      testing, but histological findings of a transbronchial lung biopsy and middle
      nasal concha supported a diagnosis of Wegener's granulomatosis. Antitubercular
      drugs and antibiotics have been reported as effective against Wegener's
      granulomatosis, but we found no evidence of benefits with antifungal agents such
      as micafungin sodium. Recently however, a case has been reported of murine
      systemic vasculitis caused by Candida albicans extract. Our case suggests the
      possible involvement of fungus in the pathogenesis and progression of Wegener's
      granulomatosis.

PMID- 20058689
TI  - [A case of gastric cancer with bilateral chylothorax].
AB  - The patient, a 77 year-old woman, visited our hospital with chief complaints of
      coughing and dyspnea. Chest radiography revealed bilateral pleural effusion
      especially on the right side, and she was admitted to our hospital to undergo a
      more thorough examination. The pleural effusion was identified as chyle. In
      cytodiagonosis, a number of adenocarcinoma cells in clumps were detected. After
      admission, her general condition worsened, and she died. Her condition was
      diagnosed as advanced gastric carcinoma on pathological dissection. Generally
      malignant lymphoma is most often reported as a cause of non-traumatic
      chylothorax. Because gastric carcinoma associated with bilateral chylothorax is
      very rare, we report the results of our study with some discussion based on a
      review of the literature.

PMID- 20058690
TI  - [A case of secondary pulmonary alveolar proteinosis associated with
      myelodysplastic syndrome, complicated with disseminated M. abscessus infection].
AB  - A 27-year-old man was admitted to our hospital complaining of a persistent high
      fever since August 2007. Chest radiography showed infiltration shadows in the
      right lower lung field. Chest CT revealed scattered small nodular shadows and
      patchy consolidations in the right lower lobe. He was diagnosed as secondary
      pulmonary alveolar proteinosis (sPAP) associated with myelodysplastic syndrome
      (MDS), confirmed by video-assisted thoracic surgery (VATS) and bone marrow
      aspiration. Sera were negative for anti-granulocyte-macrophage colony-stimulating
      factor (GM-CSF) autoantibody. He developed a subcutaneous abscess and meningitis
      caused by M. absessus after VATS. After a long-course of antibiotic therapy, an
      allogenic peripheral blood stem cell transplantation was performed. But he died
      of graft versus host disease and M. abscessus sepsis 87 days after
      transplantation.

PMID- 20058691
TI  - [A case of pulmonary infection caused by Pseudomonas aeruginosa with anorexia
      nervosa].
AB  - A 19-year-old woman with anorexia nervosa (body weight 25 kg) was admitted to our
      hospital, showing a cavitary shadow in the left upper lung field on a chest
      radiograph film. We diagnosed a pulmonary abscess caused by Pseudomonas
      aeruginosa. A few days later, exacerbation, including enlargement of the cavitary
      shadow, ipsilateral pleural effusion and bilateral infiltrations, were observed.
      Finally, by using antibiotics such as Doripenem (DRPM) and Ciprofloxacin (CPFX),
      we were able to treat the disease by bronchoscopic and thoracic drainage. This
      case suggests we should take carefully treat anorexia nervosa patients with
      pulmonary infection.

PMID- 20058692
TI  - [Paragonimus westermani infection confirmed by the detection of Paragonimus ova
      in the sputum with bilateral pleural effusion].
AB  - A 28-year-old man had a 1-year history of hemoptysis. Consequently, he underwent
      a medical examination. A right pleural effusion, left hydropneumothorax, and
      multiple pulmonary nodular shadows were found on chest radiography. During a
      detailed interview, he reported that the hemoptysis began after eating "kejang"
      (a raw crab preparation) with a friend a year previously. His peripheral blood
      eosinophil count and serum IgE level were elevated. In addition, ova were
      detected in the sputum and bilateral pleural effusion. Morphological examination
      of the ova and immunoserological examination led to the diagnosis of Paragonimus
      westermani infection. The pleural effusion could be partially drained, and his
      symptoms and radiographic results showed improvement after treatment with
      Praziquantel administered at a dose of 75 mg/(kg x day) for 3 days. After one
      month, he and his friend ate seasoned raw crabs, Paragonimus was diagnosed in his
      friend. This case suggests that on encountering a paragonimus infection, everyone
      who ate food prepared in the same kitchen should be contacted because of possible
      infection with paragonimus.

PMID- 20058693
TI  - [Small cell lung cancer with Sezary syndrome].
AB  - A 69 year-old man was admitted to our hospital with bloody sputum and abnormal
      shadows in his chest X-ray film and CT. According to the bronchoscopic
      examination, he was diagnosed as suffering from small cell lung cancer (SCLC).
      Aside from SCLC, erythroderma, lymphoadenopathy and abnormal lymphoid cells in
      his peripheral blood were recognized on admission. Considering possible disorder
      blood complications, we conducted examinations including a biopsy of the skin and
      superficial lymph nodes, which revealed the characteristics of Sezary syndrome.
      We provided local treatment for Sezary syndrome and did systemic chemotherapy
      with carboplatin and etoposide for SCLC. After four cycles of chemotherapy, the
      patient showed a partial response. We report a very rare case of SCLC with Sezary
      syndrome in which we were able to provide chemotherapy effectively and safely.

PMID- 20058694
TI  - [A case of acute interstitial pneumonia successfully treated with polymyxin B
      immobilized fiber column direct hemoperfusion].
AB  - A 65-year-old man was admitted because of rapidly progressing respiratory failure
      with diffuse ground glass opacities according to chest radiography. Acute
      interstitial pneumonia (AIP) was diagnosed because of diffuse alveolar damage
      shown by a transbronchial lungs biopsy and the exclusion of any underlying
      diseases such as infectious diseases. Because steroid pulse therapy did not
      improve his condition, he was then treated with polymyxin B-immobilized fiber
      column direct hemoperfusion (PMX-DHP), with excellent results. PMX-DHP should be
      considered as one of the treatment options for suspected AIP when steroid pulse
      therapy is ineffective.

PMID- 20058695
TI  - [A case of Churg-Strauss syndrome with methylprednisolone sodium succinate
      allergy].
AB  - A 63-year-old man with a history of therapy for asthma was admitted to a
      neighborhood hospital for treatment of a lower limb blister, accompanied by
      edema, pain and systemic fever. Churg-Strauss syndrome was diagnosed based on an
      increase in peripheral blood eosinophils, positive MPO-ANCA and other findings.
      He was given an injection of methylprednisolone sodium succinate; however his
      lower limb pain, fever and peripheral blood eosinophilia worsened. Therefore,
      steroid-resistant Churg-Strauss syndrome was diagnosed, for which he was referred
      to our hospital for more intensive treatment. His lower limb pain, fever,
      peripheral blood eosinophilia and inflammatory reactions improved immediately
      after switching treatment to oral prednisolone. Since a challenge test using an
      intravenous infusion of methylprednisolone sodium succinate worsened the lower
      limb pain, fever and peripheral blood eosinophilia, a drug allergy was diagnosed
      together with Churg-Strauss syndrome.

PMID- 20058696
TI  - [A case of small cell lung carcinoma without apparent primary lesion accompanying
      Lambert-Eaton myasthenic syndrome].
AB  - A 58-year-old man complaining of increasing weakness of muscular leg strength,
      diplopia and ptosis was admitted to our hospital. An electromyogram (EMG) showed
      typical waxing phenomenon in response to high-frequency repetitive stimulation. A
      diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) was made from his symptoms
      and EMG results. A chest CT showed mediastinal lymph node swelling. No abnormal
      mass was seen in either lung field. His serum levels of a P/Q-type anti-voltage
      gated calcium channel (VGCC) antibody, Pro-GRP, and NSE were high. FDG-PET showed
      accumulation of FDG to the mediastinal and left inguinal lymph nodes. The left
      inguinal lymphadenopathy was pathologically diagnosed as metastasis of small cell
      lung carcinoma. No tumor could be detected by bronchofiberscopy. No other distant
      metastasis was detected by brain MRI, abdominal CT, or FDG-PET. After 6 courses
      of chemotherapy for SCLC, a partial response and reduction of symptoms were
      obtained. For assessment of indistinguishable neuropathic symptoms, the possible
      diagnosis of paraneoplastic syndrome, such as LEMS, and the fact that early
      treatment for primary disease was effective, should be considered.

PMID- 20058697
TI  - [A case of rapidly growing inflammatory myofibroblastic tumor in the lung].
AB  - We report a case of a 28-year-old man with a dry cough and chest pain. Chest X
      ray film showed a huge mass in the right lung field. Computed tomography (CT) and
      magnetic resonance imaging (MRI) showed a huge mass which occupied most of the
      right thoracic cavity and invaded the superior vena cava, heart atrium and right
      pulmonary vein. Positron emission tomography (PET) showed metastasis of bone,
      right adrenal grand and lymph nodes. A tumor specimen was biopsied
      percutaneously, and the diagnosis was pathologically confirmed as an inflammatory
      myofibroblastic tumor. Immunohistochemical staining also showed an overexpression
      of ALK in the tumor. He was treated with a non-steroid anti-inflammation drug and
      steroid, but they were ineffective. He underwent chemotherapy with bleomicin,
      etoposide and cisplatin. After two cycles of chemotherapy, the tumor slightly
      reduced in size, but was eventually refractory to the regimen finally. He also
      underwent with paclitaxel and carboplatin. At present, if operative extirpation
      is not possible, there is no way to treat an inflammatory myofibroblastic tumor.
      In the future, new therapy incorporating ALK inhibitors would be expected to
      treat those cases of IMT in which local recurrences and distant metastases occur.

PMID- 20058698
TI  - [A case of postcardiac injury syndrome with repeated pleuritis after blunt chest
      trauma].
AB  - A 59-year-old man suffered blunt injury to the left chest during a fall in August
      2004. He had 5 repeated episodes of back and left chest pain in three years since
      August 2005. Since these symptoms were accompanied by left pleural effusion and
      serum inflammatory reaction, the tentative diagnosis was pleuritis. Although
      examinations of pleural effusion showed exudation with marked augmentation of
      inflammatory cells, there were no findings that suggested the cause of repetitive
      pleuritis. All symptoms were relieved within one or two weeks following
      administration of non-steroid anti-inflammatory drugs. Surgical thoracoscopy was
      carried out to investigate the cause of repeated pleuritis, and an acquired
      deficit of the left pericardium was noted. We considered this case to be
      postcardiac injury syndrome causing repeated pleuritis following blunt chest
      injury.

PMID- 20058699
TI  - [Usefulness of FDG-PET for monitoring the effects of therapy in sarcoidosis
      patients].

PMID- 20058700
TI  - [Mechanism of spliceosomal snRNP biogenesis and spinal muscular atrophy].

PMID- 20058701
TI  - [Rheb-mTOR signaling pathway involved in tumor formation].

PMID- 20058702
TI  - [Dynamics of protein evolution].

PMID- 20058703
TI  - [Tissue-specific genome-wide RNAi screen in Drosophila].

PMID- 20058704
TI  - [How animals reach their destination?: Two strategies of chemotaxis in C.
      elegans].

PMID- 20058705
TI  - [New insights into cell migration from Drosophila germ cell migration].

PMID- 20058706
TI  - [Interface between normal and transformed epithelial cells].

PMID- 20058707
TI  - [Mechanism of ubiquitin homeostasis].

PMID- 20058708
TI  - [Role of nuclear O-glycosylation in epigenetic regulation].

PMID- 20058709
TI  - [New codified regulation of arginine methylation and Akt-induced
      phosphorylation].

PMID- 20058710
TI  - [Investigating protein tertiary structures inside living cells by in-cell NMR
      spectroscopy].

PMID- 20058711
TI  - [Structure analysis of drug target proteins by neutron diffraction].

PMID- 20058712
TI  - [Mechanisms underlying the host range restriction of tobamoviruses].

PMID- 20058713
TI  - [Biosynthesis and function of long-chain polyunsaturated fatty acids in cold
      adapted bacteria].

PMID- 20058714
TI  - [Ribosome world war].

PMID- 20058715
TI  - [Application of reaction-diffusion equation to biological pattern formation].

PMID- 20058717
TI  - Homemade holiday treats.

PMID- 20058716
TI  - Why can't I lose weight? Finding your trouble spots.

PMID- 20058718
TI  - An aspirin a day. Still recommended for diabetes?

PMID- 20058719
TI  - New tools 2009.

PMID- 20058720
TI  - Accessible exercise and recreation.

PMID- 20058721
TI  - Bacon, sausage, and vegetarian alternatives.

PMID- 20058722
TI  - "Swine" flu: a new challenge.

PMID- 20058723
TI  - [Risk evaluation for malignant transformation breast intraductal papilloma].
AB  - AIM: To evaluate the risk evaluation for malignant transformation breast
      intraductal papiloma. MATERIALS AND METHODS: 277 women with pathologic nipple
      discharge were evaluated and operated on during 1994-2005. Nipple discharge was
      unilateral in 217 patients and bilateral in 60. The main diagnostic methods were
      clinical examination, ductography, discharge cytology. Cytologycal test was of
      greatest evidence. All 277 women were with small multiple papillomes. We found
      carcinoma in only 3 cases--1 intraductal and 2 invasive ductal carcinomas.
      CONCLUSION: According to our results 1.1% of our patient were with malignant
      potential.

PMID- 20058724
TI  - [Diagnostic value of the serum tumor markers CEA and CYFRA 21-1 in patients with
      non-small cell lung cancer].
AB  - SUMMARY: There is growing evidence that tumor markers can provide valuable
      diagnostic and prognostic information in patients with non-small cell lung
      cancer.Two of the most important markers are CEA and CYFRA 21-1. MATERIALS AND
      METHODS: We present 70 patients, operated at our clinic between 01.07.2007 and
      01.03.2008 (57 male, 81.4% and 13 female, 18.6%), age range: 46-75 years. Serum
      levels of the tumor markers were measured preoperatively. RESULTS: We found
      elevated levels of CEA at 26 patients (37.1%), and elevated levels of CYFRA 21-1
      at 48 patients (68.5%). CONCLUSIONS: CYFRA21-1 is a valuable tumor marker in
      patients with lung cancer. It has better sensitivity and diagnostic value in
      comparison with CEA in patients with non-small cell lung cancer.

PMID- 20058725
TI  - [Plastic reconstruction of defects in head and neck region through microsurgical
      free flaps].
AB  - The present reconstructive methods in plastic surgery include application of
      microsurgical techniques for reconstruction of tissue defects caused by various
      etiologic factors. In certain cases the free flaps turn to be the only
      therapeutic solution, or offer an alternative for achievement of a superior
      functional and aesthetic treatment. The opportunity for transfer of versatile
      tissues on microsurgical anastomoses, define the broad indications for the method
      application. We present several cases of free flap reconstructions of permanent
      tissue loss in head and neck region due to radical surgical treatment of
      neoplasms.

PMID- 20058726
TI  - [Surgical treatment in cervical spondylosis].
AB  - The most common cause for progressive cord and nerve root deterioration is
      cervical spondylosis. Symptoms often develop insidiously and are characterized by
      neck stiffness, arm pain, hand numbness, weakness in the hands and legs, gait
      disturbances--recognized in the clinical practice as cervical spondylotic
      myelopathy (CSM), cervical radiculopathy or both of them. The imaging diagnosis
      has to begin with plain radiographs of cervical spine, but magnetic resonance
      imaging (MRI) is a procedure of choice. Narrowing of the spinal canal caused by
      osteophytes, herniated disc, lig. flavum hypertrophy and myelomalacia are typical
      MRI signs. Eighty consecutive patients (46 men and 34 women) with documented CSM
      and/or radiculopathy have undergone surgery. The patients' age at surgery varied
      from 26 to 80 years (average 50 years). According to the predominant clinical
      symptoms 45 patients (34 men and 11 women) were with CSM, 35 patients (12 men and
      23 women)--with radiculopathy. The clinical evaluation was obtained by the Nurick
      Scale. Seventy three patients (91%) underwent surgery via the anterior approach
      in different levels. The following surgical procedures were applied: discectomy
      and/or osteophytectomy followed by fusion with tricortical bone autograft or
      fibrocarbone cages, with or without anterior titan plate fixation. Decompressive
      laminectomy was performed in 7 (9%) patients. Postoperative functional outcome
      and follow up was achieved in 71 (89%) patients. In 64 (90%) of them was assessed
      progressive clinical improvement; without changes were 7 (10%) patients. No early
      or late complications, induced by surgical approach, bone grafts and implants
      were observed. Although the choice of surgical treatment in cervical spondylosis
      remains controversial, currently anterior decompression and fusion is appropriate
      for many cases. We are giving priority to the anterior approach on the basis of
      our current surgical results.

PMID- 20058727
TI  - [Treatment of chronic anorectal fistulas by fibrin sealant].
AB  - The surgical treatment of chronic anorectal fistula still remains a problem and a
      challenge for the coloproctologist. Lately, about 50 articles on fibrin glue
      treatment of perianal fistulas have appeared The technique is simple and easy to
      perform can be repeated. many times as minimal surgical trauma and completely
      preserved function of the anal sphincter. AIM: To analyze retrospectively the
      efficacy of fibrin glue Tussicol in patients with chronic anorectal fistulas.
      PATIENTS AND METHODS: The method of sealing with fibrin glue has been applied to
      34 patients (29 male and 5 female mean age 48.82 +/- 2.43 years) with chronic
      perianal fistulas between January 2003 and June 2006. Patients with complicated
      fistula and those with specific etiology have been excluded. Standard colon
      cleaning without prophylactic or therapeutic antibiotics was performed. Under
      spinal or general anesthesia fistulas are observed, probed, the internal and
      external opening is identified, then curettage of the fistula channel follows,
      irrigation and filling up with fibrin glue (Tussicol Baxter). After a mean stay
      of 3.91 +/- 0.40 days in the clinic, follow up of the patients took place in
      ambulatory settings after 1 week, 1, 3 and 6 months. RESULTS: The common
      frequency of success is 73.53% (25/34). Patients with recurrent fistula did have
      poorer final results/frequency of success only 50% (2/4). Neither of the patients
      did have major postoperative problems like anal incontinence, requiring
      additional attention and treatment. CONCLUSION: Our study reapproves the complete
      safety and high effectiveness of fibrin glue treatment of anorectal fistulas. The
      procedure is easily performed and tolerated by the patients, allowing further
      expanding of therapeutic modalities of the chronic anorectal fistulas.

PMID- 20058728
TI  - [Neurocutaneous metacarpal flaps].

PMID- 20058729
TI  - [Ganglion trigeminale].

PMID- 20058731
TI  - Decompression illness medically reported by hyperbaric treatment facilities:
      cluster analysis of 1929 cases.
AB  - INTRODUCTION: The term decompression illness (DCI) describes maladies resulting
      from inadequate decompression, but there is little consensus concerning
      clinically useful DCI subclasses. Our aim was to explore an objective DCI
      classification using multivariate statistics to assess naturally associated
      clusters of DCI manifestations. We also evaluated their mapping onto other DCI
      classifications and investigated the association with therapeutic outcome.
      METHODS: We defined the optimal number of clusters using "two-step" cluster
      analysis and Bayesian information criterion with confirmation by hierarchical
      clustering with squared Euclidian distances and Ward's method. The data were 1929
      DCI cases reported by hyperbaric chambers to the Divers Alert Network (DAN
      America) from 1999-2003. RESULTS: Four robust and highly significant clusters of
      DCI manifestations were demonstrated containing 300, 741, 333, and 555 patients.
      Each cluster had characteristic manifestations. Cluster 1 was effectively pain
      only. For Cluster 2, characteristic manifestations included numbness,
      paresthesia, and decreased skin sensitivity; for Cluster 3, malaise, paralysis,
      muscular weakness, and bladder-bowel dysfunction; and for Cluster 4, hearing
      loss, localized skin swelling, tinnitus, skin rash and mottling, confusion,
      dyspnea/chokes, muscular problems, vision problems, altered consciousness,
      headache, vertigo, nausea, fatigue, dizziness, and abnormal sensations.
      DISCUSSION: Internal reliability was confirmed by arbitrarily dividing the
      dataset into two parts and repeating the analysis. The clusters mapped poorly
      onto traditional DCI categories (AGE, Type I DCS, Type II DCS), but more
      specifically onto the Perceived Severity Index (PSI). All three classification
      methods (DCI, Cluster, PSI) predicted complete relief of manifestations equally
      well. We conclude that cluster analysis is an objective method for classifying
      DCI manifestations independent of clinical judgment.

PMID- 20058732
TI  - Energetic efficiency in trained and sedentary rats after exposure to normobaric
      and hyperbaric oxygen.
AB  - INTRODUCTION: Contradictory results have been obtained regarding the beneficial
      effect of hyperbaric oxygen (HBO) on exercise performance. The purpose of this
      study was to investigate the effect of different combinations of pressure and
      time in hyperoxia on the energetic efficiency of trained and sedentary rats.
      METHODS: At the end of the training period, rats were exposed to one of three
      protocols: 1) 100% normobaric oxygen for 24 h; 2) HBO at 2 ATA for 4 h; 3) HBO at
      2.5 ATA for 6 h. After the hyperoxic exposures, V(O2max) was evaluated and
      compared with preexposure values. RESULTS: The slope of the linear section of the
      oxygen consumption-velocity curve in the trained rats was significantly steeper
      after exposure to either 100% normobaric oxygen for 24 h or HBO at 2 ATA for 4 h
      than before the exposure. The opposite was found for the sedentary rats. After
      exposure to HBO at 2.5 ATA for 6 h, the slope of the oxygen consumption-velocity
      curve in the trained rats did not differ from the pre-exposure slope. However,
      the highest velocity these rats reached was lower than their maximum velocity
      before this exposure. In the sedentary rats, the slope of the oxygen consumption
      velocity curve was found to be steeper after the 2.5 ATA exposure compared with
      the preexposure slope. CONCLUSIONS: Our results suggest that exposure to 100%
      normobaric oxygen for 24 h and HBO at 2 ATA for 4 h induces a reduction in the
      energetic efficiency of trained rats, but improves energetic efficiency in
      sedentary rats.

PMID- 20058733
TI  - Decompression from saturation using oxygen: its effect on DCS and RNA in large
      swine.
AB  - INTRODUCTION: The use of hyperbaric oxygen (HBO) to expedite decompression from
      saturation has not been proven and may increase risk of toxicity to the pulmonary
      system. To evaluate any benefit of HBO during decompression, we used a 70-kg
      swine model of saturation and examined lung tissue by microarray analysis for
      evidence of RNA regulation. METHODS: Unrestrained, non-sedated swine were
      compressed to 132 fsw (5 ATA) for 22 h to achieve saturation. Animals then
      underwent decompression on air (AirD) or HBO (HBOD) starting at 45 fsw (2.36
      ATA). Animals were evaluated for Type I and Type II decompression sickness (DCS)
      for 24 h. Control (SHAM) animals were placed in the chamber for the same
      duration, but were not compressed. Animals were sacrificed 24 h after exposure
      and total RNA was isolated from lung samples for microarray hybridizations on the
      Affymetrix platform. RESULTS: There was no evidence of Type I DCS or severe
      cardiopulmonary DCS in any of the animals; abnormal gaits were noted only in the
      HBOD group (4/9).Three genes (nidogen 2, calcitonin-like receptor, and pentaxin
      related gene) were significantly up-regulated in both the AirD and HBOD groups
      compared to controls. Three other genes (TN3, platelet basic protein, and
      cytochrome P450) were significantly down-regulated in both groups. CONCLUSIONS:
      HBO during decompression from saturation did not reduce the incidence of DCS.
      Gene regulation was apparent and similar in both the AirD and HBOD groups,
      particularly in genes related to immune function and cell signaling.

PMID- 20058734
TI  - Motion sickness with combined lateral and roll oscillation: effect of percentage
      compensation.
AB  - BACKGROUND: Both lateral acceleration and roll through the force of gravity
      produce lateral forces. On a tilting-train the tilt offsets lateral acceleration
      so as to improve the physical comfort of passengers, but motion sickness is
      believed to increase as the lateral force is reduced by increased roll (i.e., as
      the percentage roll compensation is increased). OBJECTIVES: We investigated how
      motion sickness caused by combined lateral acceleration and roll displacement
      depended on the percentage compensation. METHOD: There were 8 groups of 20
      subjects who were exposed for up to 30 min to various conditions of combined
      lateral and roll oscillation: 3 groups of 20 subjects experienced 0.2 Hz
      oscillation with 1 of 3 compensations (0, 50, or 100%) and 5 groups of 20
      subjects experienced 0.1 Hz oscillation with 1 of 5 compensations (0, 25, 50, 75,
      or 100%). With both frequencies of sinusoidal oscillation, the peak Earth-lateral
      acceleration was 1.26 m x s(-2). Subjects provided ratings of their motion
      sickness symptoms at 1-min intervals. RESULTS: The percentage compensation had
      significant effects on motion sickness. With 0.2 Hz oscillation, 50% roll
      compensation of lateral oscillation produced less motion sickness than
      uncompensated lateral oscillation, and less motion sickness than 100% roll
      compensated lateral oscillation. With 0.1 Hz oscillation, 25% roll-compensation
      of lateral oscillation produced significantly less motion sickness than either
      75% or 100% roll-compensated lateral oscillation. CONCLUSIONS: Motion sickness
      caused by combined lateral and roll oscillation is dependent on the percentage
      compensation and cannot be predicted by models based on only lateral oscillation
      or only roll oscillation.

PMID- 20058735
TI  - Cerebral cortex plasticity after 90 days of bed rest: data from TMS and fMRI.
AB  - INTRODUCTION: Microgravity animal models have demonstrated corticospinal
      plasticity; however, little is understood of its functional significance. In this
      pilot study, we explored corticospinal plasticity in a bed rest model. We
      hypothesized that the lack of weight bearing would induce cortical reorganization
      correlating with performance. METHODS: Four subjects underwent functional MRI
      (fMRI), transcranial magnetic stimulation (TMS), and functional mobility testing
      (FMT) before and after 90 d of bed rest. Recruitment curves (RC) were created by
      measuring motor evoked potentials over a range of TMS intensities with changes in
      the slope of the RC reflecting changes in corticospinal excitability. RESULTS:
      Significant leg RC slope decreases were observed on post-bed rest day 1 (P1)
      (t(2805) = -4.14, P < 0.0001), P2 (t(2805) = -6.59, P < 0.0001), P3 (t(2805) = 
      6.15, P < 0.0001), P5 (t(2805) = -7.93, P <0.0001), P8 (t(2805) = -3.30, P =
      0.001), and P12 (t(2805)= -3.33, P = 0.0009), suggesting a group decrease in
      corticospinal excitability in the immediate post-bed rest period with recovery
      approaching baseline over the following 2 wk. Significant effects were observed
      for hand RC slopes only for P2 (t(2916) = 1.97, P = 0.049), P3 (t(2916) = -2.12,
      P = 0.034), and P12 (t(2916) = -2.19, P = 0.029); no significant effects were
      observed for days P0 (t(2916) = -1.32, ns), P1 (t(2916) = 1.00, ns), P5 (t(2916)
      = -0.21, ns), or P8 (t(2916) = -0.27, ns). fMRI showed no change in activation
      for the hand but an increase in activation post-bed rest for the leg. On an
      individual basis, a more heterogeneous response was found which showed a
      potential association with performance on FMT. DISCUSSION: Results of this
      research include a better understanding of the cortical plasticity associated
      with leg disuse and may lead to applications in patient and astronaut
      rehabilitation.

PMID- 20058737
TI  - Neck strength, position sense, and motion in military helicopter crew with and
      without neck pain.
AB  - INTRODUCTION: Neck pain in military helicopter pilots and rear aircrew is an
      occupational health problem that may interfere with flying performance. The aim
      of the present study was to investigate possible differences in the physical
      abilities of the cervical spines of helicopter pilots and rear aircrew with and
      without neck pain during the previous year. METHODS: The study included 61 male
      helicopter pilots and 22 rear aircrew without neck pain (Sx-) and 17 pilots and
      17 rear aircrew with neck pain (Sx+). Active cervical range of motion (flexion
      extension, right-left rotation, and right-left lateral flexion), neck position
      sense (reposition error back to neutral and defined positions after submaximal
      cervical movement), and maximum isometric neck muscle strength (flexion,
      extension, and right and left lateral flexion) were measured. Two-way factorial
      analyses of variance were performed, in which the fixed factors were occupation
      (pilot or rear aircrew) and neck pain state (Sx+ or Sx-). RESULTS: On average,
      there was a trend toward lower values in strength [extension: 55 (19) Nm vs. 58
      (20) Nm; flexion 22 (8) Nm vs. 24 (12) Nm] and smaller cervical range of motion
      [flexion-extension: 132 degrees (19 degrees) vs. 137 degrees (15 degrees);
      rotation: 156 degrees (14 degrees) vs. 160 degrees (14 degrees)] in the total Sx+
      crew, compared to their Sx- colleagues. However, the two-way factorial ANOVA
      revealed neither significant main effects nor significant interaction effects in
      any of the measured physical abilities. CONCLUSION: The results suggest that
      having experienced neck pain was not significantly associated with differences in
      the physical abilities of the cervical spines of helicopter crew, as assessed in
      this study.

PMID- 20058736
TI  - Endothelial function and stress response after simulated dives to 18 msw
      breathing air or oxygen.
AB  - INTRODUCTION: Decompression sickness is caused by gas bubbles released upon
      decompression. These bubbles have the potential to occlude blood vessels and
      damage the vascular endothelium. The aim of this study was to quantify damage to
      the vascular endothelium resulting from decompression by measuring endothelial
      microparticles (MP) and endothelial function. METHODS: Five healthy male
      volunteers undertook a simulated (hyperbaric chamber) air dive and 1 wk later a
      second dive breathing 100% oxygen at 283 kPa (18 msw) for 60 min bottom time,
      decompressed with 5-min stops at 161 kPa (6 msw) and 131 kPa (3 msw). Endothelial
      function was tested pre- and postdive by reactive hyperemia peripheral artery
      tonometry (RH-PAT) and CD105 (Endoglin) positive MP were quantified by flow
      cytometry. Plasma E- and P-selectin, interleukin-6, and serum cortisol were also
      quantified. RESULTS: RH-PAT showed a significantly decreased endothelial function
      post-decompression after breathing air when compared to oxygen (-0.33 +/- 0.27
      vs. +0.18 +/- 0.14). CD105 MP pre- and postdive showed no change on the oxygen
      dive (460 +/- 370 to 360 +/- 163), however, they increased after breathing air
      (440 +/- 70 to 1306 +/- 359). There was no change in expression of CD105 on MP.
      Furthermore no changes were observed in plasma E- or P-selectin, IL-6, or serum
      cortisol. CONCLUSION: From the data, at least in the time frame involved, there
      appears to be no detectable physiological/stress response to decompression,
      rather decompression from breathing air probably caused mechanical damage to the
      endothelium, resulting in both MP release and a reduction in endothelial
      function.

PMID- 20058738
TI  - Aerobic exercise deconditioning and countermeasures during bed rest.
AB  - Bed rest is a well-accepted model for spaceflight in which the physiologic
      adaptations, particularly in the cardiovascular system, are studied and potential
      countermeasures can be tested. Bed rest without countermeasures results in
      reduced aerobic capacity and altered submaximal exercise responses. Aerobic
      endurance and factors which may impact prolonged exercise, however, have not been
      well studied. The initial loss of aerobic capacity is rapid, occurring in
      parallel with the loss of plasma volume. Thereafter, the reduction in maximal
      aerobic capacity proceeds more slowly and is influenced by central and peripheral
      adaptation. Exercise capacity can be maintained during bed rest and may be
      improved during recovery with appropriate countermeasures. Plasma volume
      restoration, resistive exercise, orthostatic stress, aerobic exercise, and
      aerobic exercise plus orthostatic stress all have been tested with varying levels
      of success. However, the optimal combination of elements-exercise modality,
      intensity, duration, muscle groups exercised and frequency of aerobic exercise,
      orthostatic stress, and supplementary resistive or anaerobic exercise training
      has not been systematically evaluated. Currently, frequent (at least 3 days per
      week) bouts of intense exercise (interval-style and near maximal) with
      orthostatic stress appears to be the most efficacious method to protect aerobic
      capacity during bed rest. Further refinement of protocols and countermeasure
      hardware may be necessary to insure the success of countermeasures in the unique
      environment of space.

PMID- 20058739
TI  - Severe neurological decompression sickness in a U-2 pilot.
AB  - Severe neurological decompression sickness (DCS) has been a rare entity in the
      U.S. Air Force, including the U-2 community. In over 50 yr of operation, few U-2
      pilots reported severe neurological DCS in flight despite the extreme altitudes
      at which they operate. This article describes a near-fatal case of neurological
      DCS that occurred during a combat mission. The injury left the pilot with
      permanent cognitive deficits that correlated with focal lesions present on
      magnetic resonance imaging of his brain. To our knowledge, the images presented
      herein are the first to show radiological evidence of brain injury induced by
      altitude DCS. Though only a single case, the objective and clinical findings in
      the case pilot are similar to results documented in divers suffering DCS with
      central nervous system injury and victims of traumatic brain injury. DCS will
      remain a potentially serious threat to current and future air and space
      operations.

PMID- 20058740
TI  - Myasthenia gravis and return to flying status.
AB  - INTRODUCTION: Myasthenia gravis (MG) is a common primary disorder of
      neuromuscular transmission. Although MG was once a fatal disease, today treatment
      with immunomodulating agents and cholinomimetic medications with good supportive
      care have improved the prognosis and the ability of patients to adapt to their
      workplaces, including the flight environment. CASES: The diagnosis of MG in two
      aircrew members illustrates the range of severity for MG from isolated ocular
      symptoms to relentlessly progressive generalized disease, as well as the
      unpredictability of the disease and difficulty in treatment. Nevertheless, both
      patients were returned to limited flying status. DISCUSSION: MG presents the
      potential for subtle progression with resulting effects on flight performance. In
      addition to the disease itself, flight surgeons must also consider problems
      related to treatment and its side effects. Progression and exacerbations of MG
      can develop during the course of the disease, requiring careful adjustments to
      treatment regimens. Taking all these factors into consideration, including the
      unpredictability of this disease, pilots with apparently stabilized MG should
      nevertheless be assigned only to duties during which the patient would be able to
      maintain and use his flying capabilities without risking the mission, himself,
      and other crewmembers.

PMID- 20058741
TI  - Suspected arterial gas embolism after glossopharyngeal insufflation in a breath
      hold diver.
AB  - INTRODUCTION: Many competitive breath-hold divers employ the technique of
      glossopharyngeal insufflation in order to increase their lung gas volume for a
      dive. After a maximal inspiration, using the oral and pharyngeal muscles
      repeatedly, air in the mouth is compressed and forced into the lungs. Such
      overexpansion of the lungs is associated with a high transpulmonary pressure,
      which could possibly cause pulmonary barotrauma. CASE REPORT: We report a case of
      transient neurological signs and symptoms occurring within 1 min after
      glossopharyngeal insufflation in a breath-hold diver. He complained of
      paresthesia of the right shoulder and a neurological exam revealed decreased
      sense of touch on the right side of the neck as compared to the left side. Motor
      function was normal. The course of events in this case is suggestive of arterial
      gas embolism. DISCUSSION: Although the diver recovered completely within a few
      minutes, the perspective of a more serious insult raises concerns in using the
      glossopharyngeal insufflation technique. In addition to a neurological insult,
      damage to other organs of the body has to be considered. Both acute and long-term
      negative health effects are conceivable.

PMID- 20058742
TI  - Lack of denominator data in aviation accident analysis.

PMID- 20058743
TI  - Safety management and evaluation of medical equipment: the example of aeromedical
      evacuations.

PMID- 20058744
TI  - Cell phones as a mobile medical platform.

PMID- 20058745
TI  - You're the flight surgeon: diverticulitis.

PMID- 20058746
TI  - Classics in space medicine. Brannon EW, Rockwood CA, Potts P. The influence of
      specific exercises in the prevention of debilitating musculoskeletal disorders;
      implication in physiological conditioning for prolonged weightlessness. Aerosp
      Med 1963; 34: 900-6.

PMID- 20058747
TI  - This month in aerospace medicine history.

PMID- 20058748
TI  - [Influenza A(H1N1): from question to action].

PMID- 20058749
TI  - [Why is a biosimilar medicinal product not a generic medicinal product?].

PMID- 20058750
TI  - [Parvovirus B19 infection in an adult].

PMID- 20058751
TI  - [Medical confidentiality for minors].
AB  - The new statutory provisions on the care of minors have given a legal framework
      for primary healthcare professionals. They clarify the rights of minors and their
      general application to improve the quality of the healthcare system. They are
      valuable and relevant tools for general practitioners in their day to day
      practice, and they help improve the medical care of minors, currently considered
      as a real public health problem.

PMID- 20058752
TI  - [Relapsing polychondritis and chronic myelomonocytic leukemia].

PMID- 20058753
TI  - [Cardiovascular disease in the elderly. A new public health challenge and new
      medical training needs].

PMID- 20058754
TI  - [Heart failure in elderly patients].
AB  - Heart failure is an elderly disease, interesting 10% of the population aged more
      80 years. Hypertension is this principal cause. Heart failure with preserved
      ejection fraction becomes predominant with age. Echocardiography is important to
      determine ejection fraction, left ventricular pressures and curable etiologies.
      Prognostic is more severe. Pharmacocinetic alterations need a careful utilization
      of drugs. Treatment must follow international recommendations, including use of
      renin-angiotensin-aldosterone inhibitors and betablockers. After 80 years, these
      drugs are underused. Severe salt restriction must be avoided. Strict biological
      monitoring is necessary.

PMID- 20058756
TI  - [Cardiovascular agents in the elderly: main rules to optimize their use].
AB  - Effectiveness of cardiovascular drugs in the treatment of several cardiovascular
      diseases is widely demonstrated. These drugs may be the source of potentially
      serious adverse events in the old individuals and fear of these events may partly
      explain why beta-blockers and angiotensin converting enzyme inhibitors are
      underused in elders with heart failure. Cardiovascular drugs should be prescribed
      using safe practices, including dose adjustment taking into account the renal
      function and the search for conditions like orthostatic hypotension or conduction
      disorders. Cardiovascular drugs prescribing must be done according to evidence
      based medicine in the elderly. The doses must be adjusted individually, taking
      into account the objectives and target doses, as the individual parameters as
      creatinine clearance, hydration status, blood pressure and orthostatic
      hypotension.

PMID- 20058755
TI  - [Atrial fibrillation in elderly patients].
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia in elderly
      patients: its prevalence increases with age up to 6-8% in octogenarians. A
      cardiomyopathy is associated in 50%, hypertension in 60%. Severity is attributed
      to the risk of ischaemic stroke with rates increasing up to 7% per year after 75
      years old. Quality of life is impaired and associated with numerous comorbidities
      in the elderly. Antiarrhythmic therapy is useful to slow down cardiac rate in AF.
      To reduce first or recurrent emboli, antithrombotic therapy is necessary,
      whatever the type of AF (paroxysmal or permanent). Anticoagulation is the current
      treatment modality in AF patients at high or intermediate risk, which is the case
      of most of the elderly patients. Major hemorrhage risk must be systematically
      evaluated.

PMID- 20058757
TI  - [Risk and management of anti-vitamin K in the elderly].
AB  - VKA are underused in elderly patients with thrombo-embolic disease, mainly
      because of their increased risk of bleeding. However, in most cases, evaluation
      of this risk versus the efficacy in prevention of thrombo-embolic events, should
      not lead to a therapeutic abstention. The use of VKA in frail elderly patients
      requires a specific clinical assessment before and during treatment. Moreover,
      initiation and management of VKA therapy offers some specificities in older
      patients.

PMID- 20058758
TI  - [Heart failure in the elderly].
AB  - The prevalence of coronary insufficiency increases with age and constitutes the
      leading cause of mortality. However, due to a wide range of clinical and
      electrical atypical presentations, its diagnosis is most often overlooked
      contributing to many wandering diagnostic and inadequate therapies. The fear of
      adverse events leads to the fact that elderly patients are most often under
      treated in both situations, chronical and acute. In 2008, the diagnosis of
      coronary artery disease in the elderly must use all modern means: stress test
      with thallium scintigraphy, stress echocardiography, computed tomography and even
      coronary angiography which risk of morbidity and mortality is currently very low
      due to a lot of therapeutic advancements. The age alone should not represent
      contra-indication to any of our medications, even the most aggressive, always
      keeping in mind that the risk/benefit ratio is always favourable due to the high
      risk of major cardiovascular events in the elderly population.

PMID- 20058759
TI  - [Prevention of coronary heart disease and heart failure in the elderly].
AB  - Cardiovascular diseases are responsible for disability, quality of life
      impairment and mortality in the elderly. Although it is efficient, cardiovascular
      prevention is underused in old individuals. Coronary heart disease can be
      prevented by antihypertensive agents in old subjects with hypertension, and by
      statins and antiplatelet agents in high risk subjects. In addition, betablockers
      and angiotensin converting enzyme inhibitors prevent cardiovascular events in
      patients with coronary heart disease. Heart failure can also be prevented in the
      elderly. The treatment of hypertension results in a two-fold decrease in heart
      failure incidence, even in subjects >80 years. Influenza vaccine reduces the risk
      of hospital admission for heart failure in old subjects, even in those with no
      history of cardiac or respiratory diseases. Lifestyle modifications should be
      encouraged in old individuals, especially smoking cessation, physical activity
      and mediteranean type diet, because their effects on cardiovascular health seem
      as positive in the elderly as in younger adults.

PMID- 20058761
TI  - [My NCBI: your strongbox in PubMed].

PMID- 20058760
TI  - [Cardiac conduction disorders in the elderly].
AB  - While the left bundle branch block frequently reflects underlying cardiac
      disease, conductive disorders occurring at three levels (sinus node,
      atrioventricular node, and branches of the bundle of His), are usually part of
      the aging heart. In addition, AV nodal block and sinus node dysfunction are
      readily compounded with drugs, often indispensable (beta-blockers, calcium
      blockers, digoxin, antiarrhythmic), and very common among the elderly.
      Indications for permanent pacing are accurately described and come in four
      classes: I, recommended (mandatory) - IIa, raisonable - IIb, possible - III,
      contraindicated. In 2009, 24H ECG Holter and electrophysiological study are
      generally disappointing in the positive diagnosis of syncope, so the clinical
      characteristics of syncope are essential in the decision of device implantation.
      Indeed, in the absence of ECG recorded at the time of the syncope, the diagnosis
      of BAV or BSA cannot be certain, and on the contrary, vague symptoms should not
      be attributed to a patent bradycardia of sinus or AV block origin without any
      precaution. Finally, the relationship between sinus dysfunction and carotid sinus
      syndrome remain poorly understood, dysautonomia is common among the elderly, and
      the existence of conduction disorders associated with syndrome of sleep apnea
      should not be ignored.

PMID- 20058762
TI  - [Detecting high risk pregnancy].
AB  - Antenatal care is aiming to reduce maternal land foetal mortality and morbidity.
      Maternal and foetal mortality can be due to different causes. Their knowledge
      allows identifying pregnancy (high risk pregnancy) with factors associated with
      an increased risk for maternal and/or foetal mortality and serious morbidity.
      Identification of high risk pregnancies and initiation of appropriate treatment
      and/or surveillance should improve maternal and/or foetal outcome. New risk
      factors are continuously described thanks to improvement in antenatal care and
      development in biology and cytopathology, increasing complexity in identifying
      high risk pregnancies. Level of risk can change all over the pregnancy. Ideally,
      it should be evaluated prior to the pregnancy and at each antenatal visit.
      Clinical examination is able to screen for intra-uterin growth restriction, pre
      eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of
      foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia
      and abnormal foetal growth; biological exams are used to screen for pre
      eclampsia, gestational diabetes, trisomy 21 (for which screening method just
      changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola,
      unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most
      of the preventive strategies have to be initiated during the first trimester or
      even before conception. Prevention for neural-tube defects, neonatal hypocalcemia
      and listeriosis should be performed for all women. On the opposite, some measures
      are concerning only women with risk factors such as prevention for toxoplasmosis,
      rhesus immunization (which recently changed), tobacco complications and pre
      eclampsia and intra-uterine growth factor restriction.

PMID- 20058763
TI  - [Medical education: what for?].

PMID- 20058764
TI  - [The sick elderly person: symptomatology, psychological and therapeutic
      particularities].

PMID- 20058765
TI  - [Primary and secondary bone tumors].

PMID- 20058766
TI  - [Acute and chronic headache].

PMID- 20058767
TI  - [Adrenal insufficiency].

PMID- 20058768
TI  - [Angiomas].

PMID- 20058769
TI  - [Microcrystal arthropathy].

PMID- 20058770
TI  - [Nosocomial infections].

PMID- 20058771
TI  - [A prescription for the eyes in ancient Egypt].

PMID- 20058773
TI  - Ablation of atrial fibrillation: what is the gold standard strategy?

PMID- 20058772
TI  - Atrial fibrillation ablation: importance of cavotricuspid isthmus block.
AB  - INTRODUCTION AND OBJECTIVE: Maintenance of atrial fibrillation (AF) depends on
      the presence of multiple reentrant circuits in the atria. In AF ablation, after
      pulmonary vein (PV) isolation, substrate modification can be increased by
      performing linear lesions in the left atrium that reduce the fibrillatory
      surface. A cavotricuspid isthmus (CTI) block may be an easier and safer
      alternative to left atrial lines for this purpose. Non-inducibility after AF
      ablation is associated with a higher success rate. The aim of this study is to
      assess whether CTI ablation after PV isolation reduces inducibility of atrial
      arrhythmias, particularly AF. METHODS AND RESULTS: In 29 consecutive patients (23
      male, mean age 54.6+/-11.4 years, 11 (38%) with hypertension and four (14%) with
      structural heart disease, mean left atrial dimension 43+/-6 mm) undergoing PV
      isolation for paroxysmal or persistent AF, atrial arrhythmia inducibility was
      tested before and after CTI ablation. The procedure was performed using a CARTO
      Merge mapping system, one or two Lasso catheters, an irrigated ablation catheter
      and radiofrequency energy. Atrial arrhythmia inducibility was tested with burst
      pacing down to 150 ms or atrial refractoriness from the proximal coronary sinus.
      Atrial arrhythmias were considered inducible if they persisted for more than 60
      seconds. Of the 29 patients, 26 (90%) had an inducible arrhythmia before CTI
      ablation--AF in 16, typical atrial flutter (AFL) in seven and atypical AFL in
      three. Three (10%) were non-inducible. After CTI ablation, only 11 patients (38%)
      maintained arrhythmia inducibility (p<0.001)--AF in nine and atypical AFL in two.
      There was a significant reduction of AF inducibility (16 vs. 9/29, p=0.016) and
      of combined AF and atypical AFL inducibility (19 vs. 11/29, p=0.021). After one
      year of follow-up, 23 patients (79%) had no recurrence of arrhythmia. Success
      rates were 83% in patients without and 73% in patients with inducible arrhythmias
      at the end of the procedure (p=NS). CONCLUSION: CTI ablation, in addition to PV
      isolation, significantly reduced the number of patients with inducible atrial
      arrhythmias and inducible AF.

PMID- 20058774
TI  - Left atrial volume: an old echocardiographic measure with renewed prognostic
      significance: a study in patients with dilated cardiomyopathy.
AB  - Left atrial enlargement is common in many cardiac diseases; a major determinant
      of this enlargement is left ventricular diastolic pressure. Left atrial volume
      (LAV) has recently been linked to adverse prognosis. The objective of our study
      was to assess LAV as a prognostic marker in patients with dilated cardiomyopathy
      (DCM) and to correlate LAV with other known prognostic factors such as maximum
      oxygen consumption (VO2 max) and pro-B-type natriuretic peptide (pro-BNP).
      METHODS: Our population consisted of 35 patients with DCM followed regularly in
      our hospital and with mean ejection fraction (EF) of 31+/-9.6%. All patients
      underwent routine 2D Doppler echocardiographic examination, TDI was used to
      obtain early peak velocity of the mitral annulus, and LAV was calculated using
      Simpson's method of disks. Pro-BNP was measured and cardiopulmonary exercise
      testing was also carried out. Mean follow-up was 24+/-4 months and new hospital
      admission due to heart failure, cardiac transplantation and death were considered
      cardiac events. RESULTS: All two-dimensional (left ventricular dimensions and
      volumes and EF) and conventional Doppler echocardiographic parameters (mitral
      inflow) were analyzed; mean LAV was 78.6+/-33 ml. Age and gender had no influence
      on LAV. LAV (and LAV indexed to body surface area [BSA]) showed an inverse
      correlation with VO2max (r=-0.48, p=0.008) and with pro-BNP (r=0.43, p=0.02).
      With regard to prognosis, LAV and LAV/BSA were associated with cardiac events
      (r=0.4, p=0.02), like other classic prognostic markers (EF, left ventricular
      volumes, mitral regurgitation and E/E'). The cut-off values of LAV and LAV/BSA
      for cardiac events on ROC curve analysis were 70 ml and 38 ml/m2 respectively.
      CONCLUSIONS: LAV (LAV/BSA) has incremental prognostic value in patients with
      dilated cardiomyopathy and correlates with exercise tolerance and pro-BNP.

PMID- 20058775
TI  - Results of primary angioplasty in a reference center: in-hospital outcomes.
AB  - INTRODUCTION: Primary angioplasty is accepted as the preferred treatment for
      acute myocardial infarction in the first 12 hours. However, outcomes depend to a
      large extent on the volume of activity and experience of the center. Continuous
      monitoring of methods and results obtained is therefore crucial to quality
      control. OBJECTIVE: To describe the demographic, clinical and angiographic
      characteristics as well as in-hospital outcomes of patients undergoing primary
      PCI in a high-volume Portuguese center. We also aimed to identify variables
      associated with in-hospital mortality in this population. METHODS: This was a
      retrospective registry of consecutive primary PCIs performed at Santa Marta
      Hospital between January 2001 and August 2007. Demographic, clinical, and
      angiographic characteristics and in-hospital outcomes were analyzed. Independent
      predictors of in-hospital mortality were identified by multivariate logistic
      regression analysis. RESULTS: A total of 1157 patients were identified, mean age
      61+/-12 years, 76% male. Mean pain-to-balloon time was 7.6 hours and primary
      angiographic success was 88%. Overall in-hospital mortality was 6.9%, or 5.5% if
      patients presenting in cardiogenic shock were excluded from the analysis.
      Previous history of heart failure, cardiogenic shock on admission, invasive
      ventilatory support, major hemorrhage, and age over 75 years were found to be
      associated with increased risk of in-hospital death. CONCLUSIONS: In this center
      primary PCI is effective and safe. Angiographic success rates and in-hospital
      mortality and morbidity are similar to other international registries. Patients
      at increased risk for adverse outcome can be identified by simple clinical
      characteristics such as advanced age, cardiogenic shock on admission, mechanical
      ventilation and major hemorrhage during hospitalization.

PMID- 20058776
TI  - Pulmonary hypertension in patients with ostium secundum atrial septal defect--is
      it related to echocardiographic complexity?
AB  - INTRODUCTION: Atrial septal defect (ASD) is one of the most common congenital
      heart defects. Patients may reach adulthood before being diagnosed and sometimes
      develop pulmonary hypertension (PH). According to the latest Euro Heart Survey on
      Congenital Heart Disease, 24.77% of ASD patients develop PH. The reasons for this
      evolution in only some patients are still unknown. OBJECTIVES: To assess the
      prevalence of PH in patients with ostium secundum ASD (osASD) in our district and
      to determine whether the echocardiographic morphology of the defect can be an
      indicator of evolution to PH. METHODS: The study included 181 consecutive
      patients, mean age 43.1+/-18.4 years, 65.2% women, with a diagnosis of osASD,
      referred for transthoracic and transesophageal evaluation in our center from
      January 2000 to September 2008. We assessed right atrial (RA) and ventricular
      (RV) dimensions, measured the rims and size of the ASD and determined pulmonary
      artery systolic pressure (PASP) (RV/RA gradient plus a value corresponding to the
      degree of inferior vena cava collapse). The type of shunt at the atrial level was
      assessed with intravenous injection of agitated saline. Statistical analysis was
      performed using SPSS 15.0. RESULTS: Seventy-seven patients (42.5%) had moderate
      to severe enlargement of the right heart chambers and 48 (26.5%) had pulmonary
      hypertension, defined as PASP of over 40 mmHg (equivalent to mean pulmonary
      artery pressure of 25-30 mmHg). Patients with PH were older (52.8+/-16.9 vs.
      39.0+/-17.6 years; p<0.001) and had larger defects (19.7+/-9.6 mm vs. 13.1+/-7.1
      mm; p<0.001). The proportion of women was similar in both groups (64.6% in
      patients with PH vs. 68.75% in those without; p=NS). Most patients with PH had
      ASDs with more complex shapes on echocardiography. However, some patients with
      simpler and smaller defects, such as central ASD with a diameter of <5 mm, also
      developed PH. The prevalence of PH in patients with closed ASDs was much lower:
      20.3% vs. 43.75%; p<0.002. CONCLUSIONS: According to these data, development of
      PH in patients with ASD is frequent and seems to be related to the diameter of
      the defect. However, patients with smaller and simpler defects may also develop
      PH. This seems to occur at older ages and not to be gender-dependent. Early ASD
      closure appears to prevent this.

PMID- 20058777
TI  - Effects of hypoglycemic agents on mortality and major cardiovascular outcomes in
      patients with type 2 diabetes mellitus: a narrative review [88].
AB  - Type 2 diabetes mellitus acts as a risk factor for cardiovascular disease. It has
      been hypothesized that control of plasma glucose levels would reduce
      cardiovascular disease in type 2 diabetic patients--thus lowering parameters such
      as mortality rate, myocardial infarction or stroke. A narrative review was
      carried out looking at data on mortality and cardiovascular disease outcomes,
      including myocardial infarction and stroke, associated with hypoglycemic therapy
      in type 2 diabetic patients, starting with the University Group Diabetes Trial
      (1970-1978) and ending with the Veterans Affairs Diabetes Trial (2009). The data
      reviewed in the present text fail to confirm the hypothesis presented above. No
      consistent relation between lowering plasma glucose and favorable effects either
      on mortality rate or on major cardiovascular disease has been clearly shown to
      exist. However, there are interesting data concerning drugs that lower plasma
      insulin levels, particularly metformin, but also, to a certain degree,
      pioglitazone. Also of interest are data on a possible legacy effect observed in
      the long-term follow-up of patients previously under intensive plasma glucose
      control. Consistent evidence in favor of lowering glycated hemoglobin levels to
      values under 7% also seems to be lacking at present, at least concerning
      mortality and cardiovascular outcomes. For the time being, it can be argued that
      efforts should be centered on interventions with clear evidence of benefit, such
      as treatment of hypertension or excessive weight, as well as the use of statins.

PMID- 20058778
TI  - Endothelial function and atherosclerosis: circulatory markers with clinical
      usefulness.
AB  - The healthy endothelium secretes and expresses at the surface various molecules
      which help maintain vascular wall structure and vascular homeostasis, as well as
      regulating vascular tone and leukocyte traffic. In response to various aggressive
      stimuli, the endothelial cell modulates its properties to restore vascular
      homeostasis. Usually, changes in the endothelial cell phenotype are transient and
      do not compromise the subsequent re-establishment of endothelial function.
      However, in certain pathological conditions, such as atherosclerosis, endothelial
      function is chronically disturbed, and this alteration is a critical step in the
      progression of the disease. In recent years, advances in knowledge have improved
      our understanding of the physiopathology of atherosclerosis, which is now known
      to be a dynamic and progressive process proceeding from endothelial dysfunction
      and inflammation of the vascular wall. The evolution and prognosis of
      atherosclerosis, along with the efficacy of therapeutic modalities, can be
      assessed by measuring the circulating levels of various biomarkers expressed or
      released by the endothelium. The purpose of this review is to reappraise the
      evidene concerning endothelial function under physiological conditions and in
      atherosclerosis, and to analyze markers of endothelial function with clinical
      applicability.

PMID- 20058779
TI  - Travelers on beta-blockers: is malaria chemoprophylaxis dangerous?
AB  - Classic antimalarial drugs, particularly quinine and its derivatives, are well
      known for their potential pro-arrhythmic effects. Recently developed synthetic
      antimalarials are widely used among travelers for prophylaxis. Nevertheless,
      their safety is open to question, especially for travelers under common
      cardiovascular drug therapy. We report the case of a patient admitted for
      symptomatic high-grade atrioventricular (AV) block, caused by combined therapy
      with a common malaria prophylactic drug--mefloquine--and a beta-blocker
      prescribed for a symptomatic arrhythmia. Withdrawal of the beta-blocker led to
      disappearance of the AV block despite continuation of the malaria prophylaxis.
      Mefloquine drug interactions are briefly described, particularly in terms of the
      caution needed in travelers already under beta-blocker therapy in whom
      antimalarial drug prophylaxis is recommended.

PMID- 20058780
TI  - Acute myocardial infarction after thrombolytic treatment of acute ischemic
      stroke.
AB  - Thrombolytic treatment in patients with acute ischemic stroke improves their
      clinical prognosis when administered within three hours of symptom onset. We
      report the case of a 57-year-old patient with a history of paroxysmal atrial
      fibrillation and hypertension who developed an anterior acute myocardial
      infarction after systemic thrombolytic treatment for acute ischemic stroke.
      Embolization of a pre-existing cardiac thrombus or in situ formation of a
      thrombus in a coronary artery has to be considered as a potential adverse effect
      of thrombolytic therapy in stroke patients.

PMID- 20058781
TI  - A new risk factor for infective endocarditis.
AB  - Body piercing has become an increasingly common practice in recent decades,
      especially among young people. However, it is not a completely safe procedure and
      may have serious complications such as infective endocarditis, which can occur in
      individuals with or without previous heart disease. In this paper we report a
      case of endocarditis after body piercing in a young woman with a pacemaker who
      needed surgical intervention. We also review cases of endocarditis after piercing
      described in the literature. Now that the recommendations of the American Heart
      Association for prophylaxis of infective endocarditis are more restricted, we
      discuss the need for inclusion of body piercings among procedures requiring
      prophylactic therapy in high-risk individuals.

PMID- 20058782
TI  - Aortic deformities: not all are aneurysms.

PMID- 20058783
TI  - [Regulation of in vitro and in vivo differentiation of mouse embryonic stem
      cells, embryonic germ cells, and teratocarcinoma cells by TGFb family signaling
      factors].
AB  - The activity of specific signaling and transcription factors determines the cell
      fate in normal development and in tumor transformation. The transcriptional
      profiles of gene-components of different branches of TGFbeta family signaling
      pathways were studied in experimental models of initial stages of three
      dimensional in vitro differentiation of embryonic stem cells, embryonic germ
      cells and teratocarcinoma cells and in teratomas and teratocarcinomas developed
      after their transplantation into immunodeficient Nude mice. Gene profile analysis
      of studied cell systems have revealed that expression patterns of ActivinA,
      Nodal, Lefty1, Lefty2, TGF TGFbeta1, BMP4, and GDF were identical in pluripotent
      stem cells whereas the mRNAs of all examined genes with the exception of Inhibin
      betaA/ActivinA were detected in the teratocarcinoma cells. These results indicate
      that differential activity of signaling pathways of the TGFbeta family factors
      regulates pluripotent state maintenance and pluripotent stem cell differentiation
      into the progenitors of three germ layers and extraembryonic structures and that
      normal expression pattern of TGFbeta family factors is rearranged in embryonic
      teratocarcinoma cells during tumor growth in vitro and in vivo.

PMID- 20058784
TI  - [Acid vacuolar invertase in hibernating and germinating seeds of the horse
      chestnut].
AB  - A high water content is maintained in the tissues of the axial organs of horse
      chestnut seeds after the fruit is shed and down to the time the seeds germinate.
      The plant cell vacuoles, features of whose metabolism can influence the cells'
      preparation to initiate growth in germination, are preserved. It was shown that
      the activity of acid invertase and its capacity to digest both sucrose and
      raphinose remain stable throughout the period of hibernation and the transition
      to germination, as do the molecular weight of its subunits (63 and 65 kDa) and
      multimer (500 to 550 kDa). The activity of the enzyme increases when the seeds
      swell under optimal conditions for germination; this is associated with the
      synthesis of new molecules of the enzyme in long-lived mRNA matrices. The
      storability of the enzyme in the vacuoles of hibernating seeds, together with the
      increase in its activity when seeds coming out of hibernation swell, ensures the
      rapid hydrolysis of sucrose issuing from the seeds' cotyledons, thus leading to
      increased osmotic pressure and, as a result, the beginning of cell elongation,
      i.e., germination.

PMID- 20058785
TI  - [Formation of reactive oxygen species during pollen grain germination].
AB  - The formation of reactive oxygen species in pollen at the early germination
      stage, which precedes the formation of the pollen tube, was studied. During this
      period, pollen grain is being hydrated, abruptly increasing its volume, and it
      passes from the resting state to active metabolism. Fluorescent methods have made
      it possible to reveal reactive oxygen species in the cytoplasm and inner layer of
      the pollen wall, intine. The cytoplasmic reactive oxygen species were mostly
      found in mitochondria, while extracellular ones were localized in aperture zones
      of intine, as well as in the solution surrounding pollen grains in vitro. The
      content of extracellular reactive oxygen species decreased after superoxide
      dismutase (100 units per ml) and diphenylene iodonium (100 microM), which
      indicates NADPH oxidase as one of possible producent of them. In conditions of
      suppression of extracellular reactive oxygen species production (100 microM
      diphenilene iodonium) or their promoted removal (after addition of 10 to 100
      microM ascorbic acid), the number of germinating pollen grains increased. This
      effect disappeared after further increase in the concentration of the listed
      reagents. The result is evidence of the significance of processes of
      generation/removal of extracellular reactive oxygen species for pollen
      germination.

PMID- 20058786
TI  - [Reproductive overload in D. melanogaster females--its connection with
      longevity].
AB  - The conception of individual reproduction is that fruit flies are genetically
      designed to oviposit at the highest possible rate. This rate is maintained right
      up to the moment when the organism begins to age, and the senescence is
      characterized by the reproduction rate falling exponentially. The population can
      be divided into z, s, m, and l-phenotypes depending on their resource allocation.
      The main part of the population consists of m-phenotype flies with a balanced
      resource allocation. The flies with z-phenotype are infecund; s flies do not
      reach senility; and l flies, in which the allocation is biased toward somatic
      organism maintenance, outlast the period of oviposition and die only after they
      have completely used up their reproductive potential. Individual reproductive
      patterns and reproductive phenotypes are analyzed for two D. melanogaster
      populations consisting of 493 and 474 flies. It is shown that there is a
      mortality curve for each phenotype, and that a part of the population dies out
      "prematurely" due to reproductive overload.

PMID- 20058787
TI  - [The role of protein kinase C in the establishment of the mechanism of
      vasopressin antidiuretic action in the rat kidney during mammalian postnatal
      development].
AB  - The kidney of immaturely born mammals in early postnatal development is
      insensitive to the effect of the antidiuretic hormone, vasopressin. It has been
      demonstrated that water permeability of the epithelial cells in the collecting
      ducts of a rat kidney increases during development; in this process, the response
      to desmopressin, an agonist of vasopressin V2 receptors, appears at the age of 20
      days. The observed increase in water permeability is connected with an increased
      content of the water channel's proteins aquaporins AQP2 and AQP3 in the plasma
      membrane. The calcium-dependent protein kinase C isoforms are the likely
      components of the vasopressin signal's transduction and are possibly involved in
      the mechanisms underlying the maturation of sensitivity to this hormone. The
      contents of three protein kinase C isoforms (alpha, delta, and zeta) in rats at
      different periods of their postnatal development were estimated using Western
      blot hybridization. It has been shown that the contents of protein kinase C
      isoforms alpha and delta increase with development, whereas the content of
      isoform zeta remains constant. The most likely participant of the mechanism
      providing for maturation of the cell's hormonal competence for vasopressin is the
      calcium-dependent protein kinase Ca, because it's content in the plasma membrane
      is maximal on days 20-24, which coincides with the time when the vasopressin
      action appears.

PMID- 20058788
TI  - [Retinoic acid as a regulator of planarian morphogenesis].
AB  - The effect of retinoic acid on regeneration of two species of asexual planarian
      races, Girardia tigrina and Schmidtea mediterranea, was studied. It was
      established that retinoic acids at physiological concentrations (10(-7)-10(-10)
      M) inhibit the regeneration of the head part of planarians but have no effect on
      tail blastema growth. It is shown that regeneration of the head part is inhibited
      as a result of arrest of the cell cycle of neoblasts, proliferating stem cells,
      during the transition from the G1/G0 to the S phase. Thus, the morphogenetic role
      of retinoic acids in planarians, primitive bilaterally symmetrical animals, has
      been demonstrated.

PMID- 20058789
TI  - [Age-dependent changes in the concentration of active sex steroids, their
      precursors, metabolites, and regulating agents in male blood].
AB  - Blood concentrations of hormone-inactive and active sex-steroid metabolites and
      their precursors were measured, taking into account changes in protein-peptide
      hormones that control the reproductive axis (in a total of 14 parameters) in men
      in the 18- to 72-year-old age interval. A significant decrease in the blood
      concentration of unutilized precursors of active sex steroids (pregnenolone,
      progesterone, dehydroepiandrosterone, and its sulfate), unbound testosterone,
      androstenedione (an inactive metabolite of testosterone), and an active
      metabolite, 5alpha-dihydrotestosterone was determined after the age of 35.
      However, the level of total testosterone and of estradiol (another active
      metabolite of testosterone) remained constant. The systems regulating the
      production of active sex steroids resisted a higher load, causing the luteinizing
      and follicle-stimulating hypophyseal hormones and activin of steroidogenic glands
      to increase and correlate positively with age; these hormones correlated
      negatively with certain sex steroids that realize negative feedback. A decrease
      in the level of adrenocorticotropic hypophyseal hormone with age suggests a more
      substantial role for adrenal glands as compared to that of testicles in reducing
      the blood concentration of active sex steroids. In general, despite the reduced
      activity of steroidogenic glands in 60- to 70-year-old men, their testosterone
      and estradiol concentrations remain unchanged, due to coordinated growth in the
      concentration of luteinizing and follicle-stimulating hypophyseal hormones, and
      to the activin of steroidogenic glands, which stimulated sex steroid
      biosynthesis. At the same time, the androgen effect was inhibited as a result of
      reduced levels of unbound testosterone and 5alpha-dihydrotestosterone.

PMID- 20058790
TI  - [Melatonin effect on the regeneration of the flatworm Girardia tigrina].
AB  - The melatonin effect on the anterior and posterior ends of a free-living flatworm
      Girardia tigrina was studied, as well as the variability of the mitotic activity
      of the stem cells (neoblasts) in the anterior and posterior postblasteme. This
      hormone may inhibit the regeneration of the anterior end of the animal in the
      physiologic-friendly concentrations of 10(-10)-10(-15) M by suppressing the
      mitotic activity of the neoblasts. This hormone does not affect the posterior
      end's regeneration; thus, its regeneration effect is significantly elective.

PMID- 20058791
TI  - [The 15th school on the topical problems in developmental biology and
      biotechnology].

PMID- 20058792
TI  - [DNA barcoding is a new approach in comparative genomics of plants].
AB  - DNA barcoding was proposed as a method for recognition and identification of
      eukaryotic species through comparison of sequences of a standard short DNA
      fragment--DNA barcode--from an unknown specimen to a library of reference
      sequences from known species. This allows identifying an organism at any stage of
      development from a very small tissue sample, fresh or conserved many years ago.
      Molecular identification of plant samples can be used in various scientific and
      applied fields. It would also help to find new species, which is particularly
      important for cryptogamic plants. An optimal DNA barcode region is a small
      fragment present in all species of a major taxonomic group, having invariable
      nucleotide sequence in all members of the same species, but with sufficient
      variation to discriminate among the species. This fragment should be flanked by
      low-variable regions for use of universal primers in PCR for amplification and
      sequencing. The DNA barcode that is well established in animals is a sequence of
      a fragment of the mitochondrial cytochrome c oxidase gene CO1. However, searching
      for DNA barcode in plants proved to be a more challenging task. No DNA region
      universally suitable for all plants and meeting all of the necessary criteria has
      been found. Apparently, a multilocus or two-stage approach should be applied for
      this purpose. Several fragments of the chloroplast genome (trnH-psbA, matK, rpoC,
      rpoB, rbcL) in combinations of two or three regions were suggested as candidate
      regions with highest potential, but more representative samples should be
      examined to choose the best candidate. The possibility is discussed to use as DNA
      barcode internal transcribed spacers (ITS) of nuclear rRNA genes, which are
      highly variable, widely employed in molecular phylogenetic studies at the species
      level, but also have some limitations.

PMID- 20058793
TI  - [Molecular genetic mechanisms used by legumes to control early stages of mutually
      beneficial (mutualistic) symbiosis].
AB  - Recent data on the plant control of early stages of mutually beneficial
      (mutualistic) symbioses of legumes, the mechanisms of perception and transmission
      of the microsymbiont's molecular signals in the macrosymbiont's cells, and
      induction of the genetic programs of the development of symbiotic compartments
      and organs of the plant are summarized. It is demonstrated that the genetic
      system of the plant controlling the development of nitrogen-fixing symbiosis of
      legumes (symbiotic root nodules), which emerged 70-80 Ma ago, has undoubtedly
      evolved on the basis of the genetic system controlling the development of the
      symbiosis with arbuscular mycorrhizal fungi (which emerged 40-500 Ma ago.
      Interactions between genes and between gene products, as well as exchange of
      molecular signals, form the basis of mutually beneficial (mutualistic) plant
      bacterium interactions. Even in the case of a highly specific nitrogen-fixing
      symbiosis of legumes (symbiotic nodules), the receptors perceiving the signal
      from root-nodule bacteria may function in different ways. The development of
      arbuscular mycorrhiza and nitrogen-fixing symbiosis in legumes is a multistep
      process involving hundreds of genes of both the macro- and microsymbionts. For
      the symbioses to develop successfully, these genes should act in a coordinated
      way in the newly formed superorganismal system. Further studies are necessary to
      shed light onto the complexity of the plant genetic control of the development of
      mutualistic symbioses in legumes and provide information required for improving
      their functions in adaptive plant-breeding systems.

PMID- 20058794
TI  - [Specific features of T-DNA insertion regions in transgenic plants].
AB  - Experimental data from analysis of exogenous DNA (T-DNA) insertion sites in
      transgenic plants are summarized. Arguments are considered in favor and against
      the existence of genome DNA regions preferred for transgene integration that are
      determined by distinctive features characterizing the organization and nucleotide
      composition of the plant genome and the structure and conformational state of the
      chromatin. The main stages of T-DNA integration into a plant chromosome and
      possible molecular mechanisms of this process are discussed.

PMID- 20058795
TI  - [Genetics of plant development: integrating data from different observations and
      experiments in databases].
AB  - Genetics of plant development as a scientific discipline integrates experimental
      evidence from such different fields of biology as embryology, plant anatomy,
      molecular biology, and genetics, and studies their relationships with ontogeny.
      To date, traditional publication of scientific studies in form of articles is
      supplemented by presenting the results of extensive genome-scale experiments in
      genomics, transcriptomics, proteomics, and phenomics in databases. The
      information burst, cased both by genome-scale studies and growth in the number of
      publications, requires the development of general standards of annotating data
      from different sources for their integration and comparison. In this review, we
      present classification and analysis of existing databases, in which the user can
      find various kinds of information essential for studying developmental genetics
      of plants, and discuss problems of data integration both within the informational
      resources and among them.

PMID- 20058796
TI  - [The transcriptome analysis of barley (Hordeum vulgare L.) using the Affymetrix
      Barley1 GeneChip].
AB  - An alternative to complete genome sequencing is development and analysis of ESTs
      fragments of transcribed coding DNA sequences. The EST collections also enhanced
      the development of cDNA microarray technologies, which make possible assessing
      the transcription levels of several thousand genes in a studied tissue of an
      organism in the same experiment. This paper provides an overview of the results
      of experiments with a barley microarray, Affymetrix Barley1 GeneChip. The
      variation in transcription levels of over 22000 genes in germinating barley grain
      of 150 barley double haploid lines produced by crossing cultivars Steptoe and
      Morex. Variation in gene expression of each gene is a quantitative trait, which
      can be mapped in population of double haploids as the genetic loci determining
      its variation (expressed QTL or eQTL). A regulatory locus (eQTL) can colocalize
      with the corresponding gene on genetic map (cis-eQTL) or be distant from it,
      frequently on another chromosome (trans-eQTL). Thus, it is possible to detect and
      analyze cis- and trans-regulatory loci for genes on a genome-wide scale. The
      design of the Affymetrix oligonucleotide arrays makes it possible not only to
      concurrently test the transcription level of several thousand genes, but also to
      simultaneously detect the polymorphic regions in cDNA sequences, thereby finding
      a considerable fraction of all nucleotide substitutions between the compared
      genotypes. Two types of data (the expression levels of several thousand genes and
      the presence of polymorphic sites in their sequences) can be obtained
      concurrently when processing the results of the same experiment. The details of
      both procedures are illustrated with explanatory examples.

PMID- 20058797
TI  - [The unique genome of two-chromosome grasses Zingeria and Colpodium, its origin,
      and evolution].
AB  - Chromosome C-banding and two-color fluorescent in situ hybridization (FISH) were
      used to compare the chromosomes, to identify the chromosomal localization of the
      45S and 5S rRNA genes, and to analyze the sequences of internal transcribed
      spacers 1 and 2 (ITS1 and ITS2) of the 45S rRNA genes in the genomes of grasses
      Zingeria biebersteiniana (2n = 4), Z. pisidica, Z. trichopoda (2n = 8), Colpodium
      versicolor (2n = 4), and Catabrosella variegata (syn. Colpodium variegatum) (2n =
      10). Differences in C-banding pattern were observed for two Z. biebersteiniana
      accessions from different localities. Similar C-banding patterns of chromosomes 1
      and 2 were demonstrated for the Z. pisidica and Z. biebersteininana karyotypes.
      Chromosome C banding and localization of the 45S and 5S rRNA genes on the
      chromosomes of the two Zingeria species confirmed the assumption that Z. pisidica
      is an allotetraploid with one of the subgenomes similar to the Z. biebersteiniana
      genome. ITS comparisons showed that the unique two-chromosome grasses (x = 2)-Z.
      biebersteiniana (2n = 4), Z. trichopoda (2n = 8), Z. pisidica (2n = 8), and C.
      versicolor (2n = 4), which were earlier assigned to different tribes of subtribes
      of the family Poaceae-represent two closely related genera, the genetic distance
      (p-distance) between their ITSs being only 1.2-4.4%. The Zingeria species and C.
      versicolor formed a common clade with Catabrosella araratica (2n = 42, x = 7) on
      a molecular phylogenetic tree. Thus, the karyotypes of Zingeria and Colpodium,
      which have the lowest known basic chromosome number (x = 2), proved to be
      monophyletic, rather than originating from different phylogenetic lineages.

PMID- 20058798
TI  - [Chromosomal organization of the genomes of small-chromosome plants].
AB  - An effective approach to study the chromosome organization in genomes of plants
      with small chromosomes and/or with low-informative C-banding patterns was
      developed in the course of investigation of the karyotypes of cotton plant,
      camomile, flax, and pea. To increase the resolving power of chromosome analysis,
      methods were worked out for revealing early replication patterns on chromosomes
      and for artificial impairment of mitotic chromosome condensation with the use of
      a DNA intercalator, 9-aminoacridine (9-AMA). To estimate polymorphism of the
      patterns of C-banding of small chromosomes on preparations obtained with the use
      of 9-AMA, it is necessary to choose a length interval that must not exceed three
      average sizes of metaphase chromosomes without the intercalator. The use of 9-AMA
      increases the resolution of differential C- and OR-banding and the precision of
      physical chromosome mapping by the FISH method. Of particular importance in
      studying small chromosomes is optimization of the computer-aided methods used to
      obtain and process chromosome images. The complex approach developed for analysis
      of the chromosome organization in plant genomes was used to study the karyotypes
      of 24 species of the genus Linum L. It permitted their chromosomes to be
      identified for the first time, and, in addition, B chromosomes were discovered
      and studied in the karyotypes of the species of the section Syllinum. By
      similarity of the karyotypes, the studied flax species were distributed in eight
      groups in agreement with the clusterization of these species according to the
      results of RAPD analysis performed in parallel. Systematic positions and
      phylogenetic relationships of the studied flax species were verified. Out results
      can serve as an important argument in favour of the proposal to develop a special
      program for sequencing the genome of cultivated flax (L. usitatissimum L.), which
      is a major representative of small-chromosome species.

PMID- 20058799
TI  - [Genetic differentiation of hexaploid wheat inferred from analysis of
      microsatellite loci].
AB  - Landraces of wheat can serve as important potential sources for extending the
      genetic basis of selection cultivars. Analysis of microsatellites and typing of
      polymorphism in a representative sample of 347 genotypes, including landraces and
      selection cultivars, was performed using a set of 38 selected oligonucleotide
      primer pairs. Classification of genotypes with respect to the level of their
      similarity was performed using cluster analysis. The data obtained pointed to
      genetic differentiation of hexaploid wheat. The groups of cultivars, the
      formation of which was thought to be associated with the main old areas of wheat
      cultivation in Europe and Asia, were identified. The basis of each of the groups
      was formed by landraces of common wheat. The differences between the groups
      identified were associated with multiple changes in the wheat genome and were
      expressed as quantitative differences in the allele frequencies of microsatellite
      loci. The results of the study are of interest in terms of understanding the
      structure of wheat genetic diversity and revealing the pathways of evolution of
      this culture.

PMID- 20058800
TI  - [Phylogeny of the A genomes of wild and cultivated wheat species].
AB  - Diploid species of the genus Triticum L. are its most ancient representatives and
      have the A genome, which was more recently inherited by all polyploid species.
      Studies of the phylogenetic relationships among diploid and polyploid wheat
      species help to identify the donors of elementary genomes and to examine the
      species specificity of genomes. In this study, molecular analysis of the variable
      sequences of three nuclear genes (Acc-1, Pgk-1, and Vrn-1) was performed for wild
      and cultivated wheat species, including both diploids and polyploids. Based on
      the sequence variations found in the genes, clear differences were observed among
      elementary genomes, but almost no polymorphism was detected within each genome in
      polyploids. At the same time, the regions of the three genes proved to be rather
      heterogeneous in the diploid species Triticum boeoticum Boiss., T. urartu Thum.
      ex Gandil., and T. monococcum L., thus representing mixed populations. A genome
      variant identical to the A genome of polyploid species was observed only in T.
      urartu. Species-specific molecular markers discriminating the diploid species
      were not found. Analysis of the inheritance of morphological characters also
      failed to identify a species-specific character for the three diploid wheat
      species apart from the hairy leaf blade type, described previously.

PMID- 20058801
TI  - [Chromosome synteny of the A genome of two evolutionary wheat lines].
AB  - In order to estimate synteny between A(t) and A polyploid wheat genomes belonging
      to different evolutionary lines (Timopheevi and Emmer), saturation of chromosome
      maps of Triticum timopheevii A(t) genome by molecular markers has been conducted.
      Totally, 179 EST-SSR and 48 genomic SSR-markers have been used with the following
      integration of 13 and 7 markers correspondingly into chromosome maps of A(t)
      genome. EST-SSR showed higher transferability and lower polymorphism than genomic
      SSR markers. The chromosome maps designed were compared to maps of homoeologous
      chromosome group of the T. aestivum A genome. No disturbances of colinearity,
      i.e., of the order of markers within the chromosome segments on which they had
      been previously mapped, were observed. According to the quantity assessment of
      markers amplifying in homoeologous chromosomes, the maximum divergence was
      detected in two groups (4A(t)/4A and 3A(t)/3A) among the seven chromosomes
      examined in the A(t) and A genomes. Comparison of molecular genetic mapping
      results with the published results of studying meiosis of F1 hybrids and the
      frequency of chromosomes substitution in introgressive T. aestivum x T.
      timopheevii lines suggest that individual chromosomes of the At and A genomes
      evolve differently. Translocations were shown to introduce the major impact on
      the divergence of 4A(t)/4A and 6A(t)/6A chromosomes, while mutations of the
      primary DNA structure, on the divergence of homoeologous group 3 chromosomes. The
      level of reorganization of other chromosomes during the evolution in the A(t) and
      A genomes was significantly lower.

PMID- 20058802
TI  - [Intraspecific divergence in wheats of the Emmer group using in situ
      hybridization with the Spelt1 family of tandem repeats].
AB  - Fluorescence in situ hybridization (FISH) was used to study the distribution of
      Spelt1 repetitive DNA sequences on chromosomes of 37 accessions representing
      eight polyploidy wheat species of the Emmer evolutionary lineage: Triticum
      dicoccoides Korn, T. dicoccum (Schrank) Schuebel, T. durum Desf., T. polonicum
      L., T. carthlicum Nevski, T. aethiopicum Jabbz., T. aestivum L., and T. spelta L.
      Substantial polymorphism in the number, distribution, and the sizes of the Spelt1
      loci was revealed. On the chromosomes of the accessions examined, Spelt1 tandem
      repeats were found in seven different positions (per haploid chromosome set).
      These were "potential hybridization sites", including the subtelomeric regions of
      either short or long arms of chromosomes 2A and 6B, the short arm of chromosome
      1B, and the long arms of chromosomes 2B and 3B. However, in individual genotypes,
      only from one to three Spelt1 loci were revealed. Furthermore, no hybridization
      with Spelt1 probe was detected on chromosomes from 12 accessions. Thus, the total
      number of Spelt1 sites in karyotypes varied from zero to three, with the average
      number of 1.16. This was substantially lower than in the species of the
      Timopheevi section and diploid Aegilops speltoides Tausch, a putative donor of
      the B genome. The decrease of the content of Spelt1 sequences in the genomes of
      the Emmer group wheats in comparison with the species of the Timopheevii group
      and diploid Ae. speltoides was assumed to result from the repetitive sequences
      reorganization during polyploidization and the repeat elimination during wheat
      evolution.

PMID- 20058803
TI  - [Impairment of homologous chromosome synapsis in meiosis in rye Secale cereale L.
      caused by a recessive mutation of the sy18 gene].
AB  - AExpression and inheritance of the sy18 mutation causing impairment of synapsis
      homology were studied. It was established that the abnormal phenotype is
      determined by a recessive allele of the sy18 gene. Univalents and multivalents
      are observed in homozygotes for this mutant allele. According to the electron
      microscopic analysis of synaptonemal complexes in mutants, homologous synapsis
      occurs together with nonhomologous synapsis. The sy18 gene was found to have no
      allelism with asynaptic genes sy1 and sy9 and with genes sy10 and sy19 causing,
      like sy18, disturbances in synapsis homology.

PMID- 20058804
TI  - [Independent species status of Iris vorobievii N.S. Pavlova, Iris mandshurica
      Maxim., and Iris humilis Georgi (Iridaceae): evidence from the nuclear and
      chloroplast genomes].
AB  - Nuclear (RAPD) and chloroplast (trnH-psbA, atpB-rbcL, rps4, trnL-trnF, and trnS
      trnG) molecular DNA markers were used to study the populations of closely related
      species of the genus Iris L.: Iris vorobievii N.S. Pavlova, I. mandshurica
      Maxim., and I. humilis Georgi. An analysis of 243 RAPD fragments made it possible
      to calculate the main population parameters and to identify species-specific RAPD
      markers. Differences that discriminated the species were found in all but one
      (trnL-trnF) cpDNA region. The total length of the four variable cpDNA regions was
      3640 bp, indels included. Their variation was low. A total of 22 variable sites
      (0.63%) were found; of these, 13 were parsimony informative and 9 were
      noninformative. Analysis of molecular variance (AMOVA) revealed significantly (P
      < 0.0001) high differentiation of both nuclear (F(ST) = 0.681) and chloroplast
      (F(ST) = 0.854) genomes for the species examined. Thus, a multigene approach
      confirmed the independent species status of I. vorobievii, I. mandshurica, and I.
      humilis and showed that I. vorobievii and I. mandshurica, but not I. humilis, are
      found in Primorye.

PMID- 20058805
TI  - [Structural organization of telomeres in various kinds of organisms].
AB  - The review considers the structure of telomeres, terminal regions of linear of
      linear chromosomal DNA. Features of nucleotide organization of telomeric DNA in
      different species are shown. Special attention is given to analysis of functions
      of separate mammal and Saccharomyces cerevisiae telomere proteins, and their role
      in telomere length regulation and protection against degradation.

PMID- 20058806
TI  - [Characteristics of the signal transduction in parasitic lower eukaryotes].
AB  - The review summarizes current data about pathways of the signal transduction in
      parasitic unicellular eukaryotes at the initial stage of the invasion and during
      their intracellular adaptation, growth and replication. The role of the factors
      that influence virulence of the unicellular parasites is reviewed. A special
      attention is paid to aspects of intracellular communications of the parasites and
      host cells.

PMID- 20058807
TI  - [Cytoskeleton structures and adhesion properties of human stromal precursors
      under conditions of simulated microgravity].
AB  - Cytoskeletal alterations occur is several cell types including lymphocytes, glial
      cells, and osteoblasts, during spaceflight and under simulated microgravity
      (SMG). One of the potential mechanisms of cytoskeletal gravisensitivity of a cell
      is disruption of extracellular matrix and integrin interactions. Therefore, we
      investigated the effects of SMG on F-actin cytoskeleton structure, vinculin focal
      adhesions, expression of some integrin subtypes and cellular adhesion molecules
      in mesenchymal stem cells (hMSCs) derived from human bone marrow in vitro.
      Simulated microgravity was produced by RPM (manufactured by Dutch Space, The
      Netherlands). Culture flasks with MSCs were settled on the inner platform of RPM
      for 30 minutes, 6, 24, 48 and 120 h. The results have shown that actin
      cytoskeleton is very fast reorganized even after 30 minutes of simulated
      microgravity. The number of cells with disrupted actin cytoskeleton steadily
      increased with the increasing exposure time. However these changes were
      reversible because the cells partly recovered their F-actin structure after 120
      hours-exposure. In addition, we observed vinculin redistribution inside the cells
      after 6 hours and subsequent terms of exposures. This process was accompanied
      with increasing of fluorescence intensity of cells. The expression of integrin
      alpha2 increased after exposure in RPM. Also we observed decrease in the number
      of VCAM-1-positive cells and changes in the expression of ICAM-1. Thus, our
      findings indicate that SMG leads to reversible microfilament alterations of hMSCs
      and alters adhesion properties of this type of cells.

PMID- 20058808
TI  - [Influence of clinorotation on embryoid bodies morphology].
AB  - The compensative effects of gravitation at the first stages of embryonic
      development stages have been investigated using slow clinorotation of embryoid
      bodies from mouse R1 stem cell lines. Semithin sections (1-2 microm) analysis and
      electron microscopy study of embryonic bodies cells allowed to reveal
      morphological features of cells at different maturation stages. Significant
      decrease in the number of embryonic stem cells undergoing apoptosis as well as
      noticeable reduction of "lacunas" relative areas were found in clinorotated
      embryonic bodies compared to control. We propose that large cyst absence may be
      caused by initial differentiation and morphogenesis stages delay associated with
      autophagy processes in embryonic bodies.

PMID- 20058809
TI  - [Yeast cell ultrastructure after amiodarone treatment].
AB  - [Amiodarone is used as a pharmaceutical substance for treating a number of
      diseases. However it is known that structural and functional disturbances are
      caused by amiodarone in patient's tissues. Here particular features of amiodarone
      effect are studied in yeast Saccharomyces cerevisiae, where amiodarone was shown
      to cause apoptosis. Electron-microscopic study of yeast cells after amiodarone
      treatment reveals a significant increase in lipid particle number which can lead
      to formation of a structural complex by interacting with membranous organelles of
      a cell. Amiodarone causes the appearance of small and separated slightly swollen
      mitochondria. Chro-matin displacement to the periphery of nucleus, nuclear
      sectioning and nuclear envelope disturbances are observed in the cells under
      these conditions. The detected cell ultrastructure alterations in the S.
      cerevisiae are considered to be specific response to the phospholipidosis and
      apoptosis caused by amiodarone.

PMID- 20058810
TI  - [Mosaic expression of the lacZ reporter-gene under control of 5'-regulatory
      sequences of the alpha-S1-casein gene in transgenic mice].
AB  - Phenomenon of mosaic expression at cellular level is widely presented in tissues
      and organs of transgenic animals. The communication is concerned a study of the
      mosaics in transgenic mice carrying the lacZ reporter-gene under control of the
      bovine and goat alpha-S1-casein genes with 5'-flanked sequences of various ex
      tent: pCLZ1--721bp, pCLZ2-- 2001 bp and pCLZ3 3409 bp constructs. Five transgenic
      founders were generated by injection of the recombinant DNA into zygotes: pCLZ 1 
      N 16, pCLZ2 - N 37 and pCLZ3 N 7, N 36, and N 48. Positive for J3-galactosidase
      activity cells were detected in lactating mammary glands of all transgenic
      females, however, distribution of the positive cells was variable. We observed
      two types of mosaics: clonal or "lobule" type with positive cells filling the
      whole of the globule or stochastic type with single positive cells scattered over
      one or different lobules. Two types of mosaics were characteristic of all the
      transgenic animals, although, females carrying the pCLZ2 transgene showed
      "lobule" type more often than transgenic animals with the transgenes pCLZ and
      pCLZ3. It is suggested that the stochastic type of mosaics occurs in the cells at
      terminal stage of differentiation, whereas the <<lobule>> type arises from
      positive for P-galactosidase proliferating precursors. Analysis of the
      inheritance of the transgenes in different lines demonstrated that the pCLZl
      transgene was inserted in the X-chromosome of the founder whereas the other two
      localized in autosomes. Localization of the pCLZl transgene in the X-chromosome
      did not influence the mosaicism; it was similar to that of transgenic animals
      carrying the transgenes in autosomes. Ectopic expression of the reporter-gene was
      detected in mandibular glands from the offsprings of the founders N 16 and N 37
      only, as well as in atrezed follicles in N 37. The weak ectopic expression
      saggests that the 5 S-flanked regulatory sequences used in the constructs are
      able to provide perfect tissue-specific expression of the reporter-gene.

PMID- 20058811
TI  - [Characterization of transposon mariner from the Himasthla elongata genome].
AB  - A novel transposable element Hemar 1 was identified and characterized in the
      genome of Himasthla elongata flatworm. This element is a member of mariner
      family; it belongs to capitata subfamily and highly homologues to turbellarian
      worm Dugesia tigrina mariner transposon. Hemar 1 is a dispersed repeat and
      accounts for about 0.01% of H. elongata genome. Identified element Hemar 1
      represents useful tool for investigation of functions of the mobile elements in
      H. elongata genome.

PMID- 20058812
TI  - [B chromosome number polymorphism and mosaicism of the Korean field mouse
      Apodemus peninsulae (rodentia) in the Russian Far East].
AB  - Karyotype analysis of the Apodemus peninsulae (n = 355) from 41 trapping points
      from the Russian Far East made it possible to reveal B chromosomes in 87.9 %
      animals, where 61.7% among them were mosaics. Different levels of B chromosome
      numbers variability such as inter- and intrapopulational, and intraindividual
      (mosaicism) as well have been studied. It has been revealed that frequencies of
      occurrence of individuals with B chromosomes and mosaicism were not constant
      between different population's samples. The range of the modal B chromosome
      number variations and the xB index variability (from 0 to 4, xB averaged 1.67)
      both have been fist investigated in different samples and populations of this
      species. Individuals with the predominant B chromosome numbers (as a rule, 0-2)
      have been revealed in both groups of animals (with stable and mosaic karyotypes)
      but the frequency was different in the geographical regions. The spectra of B
      chromosome variability were wider in mosaics (0-7) in comparison with animals
      with stable karyotypes (0-4). High frequency of individuals with B chromosomes
      and with mosaicism, and their significance for the species is discussed. The
      adaptive role of the low number of B chromosomes (1-2) is assumed and the B
      chromosome system seems not to be balanced in the species in whole.

PMID- 20058813
TI  - [Steroidogenesis-related proteins expression in skin cells].
AB  - Peripheral benzodiazepine receptor (PBR, TsPO) is an outer mitochondrial membrane
      protein which is implicated in steroid biosynthesis regulation, apoptosis and
      cell proliferation. Immunocytochemical assay revealed decreased levels of PBR,
      its endogenous ligand DBI and cytochrome P450scc in malignant skin cells in
      comparison to normal keratinocytes and melanocytes. These data indicate
      diminished steroidogenesis in skin cancer.

PMID- 20058814
TI  - [Cytological, morphological and functional changes of Russian sturgeons's
      (Acipenser guldenshtadti) sperm cells after cryopreservation].
AB  - The article presents some experimental results concerning the problem of genetic
      conservation of valuable and endangered animal species. Biotechnical development
      of the cryopreservation of spermatic cells for the purpose of their extended
      storage at low and ultra low temperatures is a priority line of the
      investigations in the topical area and implies creation of animal genomes
      cryobanks. It is known that water crystals of plasma and the cell itself often
      cause the spermatholysis in the course of freezing. That is why the search for
      the substances with cryoprotective properties continues up to the present moment.
      In this study, we investigated cryoprotective properties of glycerin, dimethyl
      sulfoxide and heparin in different proportions using spermatic fluid of sturgeon
      Acipenser guldenshtadti (Brandt). These results obtained were compared with the
      cryoprotectors of well-known composition. In addition, freezing and storage of
      the spermatic fluid were executed in two variations: at low and ultralow
      temperatures. Cold tolerance of the sperm cells was estimated by the sperm
      mobility and by light microscopy morphological analysis of the cells. It was
      shown to be linked to the composition of cryoprotectors. The heaviest violations
      were observed under addition of osmotic active substances, some inorganic
      compounds among them. Principle of our modification is based on that we used
      fluid substances: glycerin, dimethyl sulfoxide, heparin eliminating water as a
      solvent. The results obtained showed that our modified cryoprotectors and the
      standard cryoprotectors had equal efficiency. The article also presents the data
      on the spermatic fluid freezing at low temperature. They are important in case of
      modern freezing systems.

PMID- 20058815
TI  - [Signaling mechanism of NO-induced increase in cardiac tolerance to ischemia
      reperfusion].
AB  - In the review it is analyzes published data on the signaling mechanism of
      cardioprotective impact of nitric oxide. It was shown that nitric oxide exhibited
      a rapid and a delayed cardioprotective effects. In the rapid effect, endothelial
      NO-synthase (NOS) is involved was involved as well as guanylate cyclase, cGMP,
      kinase G, kinase C, PI3-kinase, Akt-kinase, mitochondrial ATP-sensitive K+
      channel, reactive oxygen species, MPT-pore. Delayed cardioprotective effect of
      NOS required synthesis of proteins de novo. In this process, transcription
      factors NF-KB, STAT1/3, HIF-1 are involved. Some published data state that
      peroxynitrite, cGMP, kinase G, kinase C, Src kinase, p38 kinase, ERK-kinase can
      be involved in delayed cardioprotective effect of NOS. The cardioprotective
      impact of nitric oxide was shown to depend on enhancement in expression of NOS,
      cyclooxygenase-2 and Blc-2 protein which inhibits MPT-pore.

PMID- 20058816
TI  - [Baroreceptor reflex and arterial hypertension].
AB  - The vaso-renal arterial hypertension was produced in in the "two kidneys-one
      clip" model in experiments on Wistar male rats. This procedure was performed both
      in rats with intact mechanoreceptor zones of large vessels and the rats with
      destroyed baroreceptors. The date obtained indicate that in rats with cutting of
      "buffer" nerves the arterial hypertension after clipping renal artery occurred in
      all rats while in rats with intact sino-carotid and aortal nerves arterial
      hypertension developed only in 39% of the animals. It is concluded that
      baroreceptor reflex counteract development of vaso-renal arterial hypertension
      and can take part in long term regulation of blood pressure.

PMID- 20058817
TI  - [About sensitive of erythroblastic islands bone marrow of polycythemic reds to
      erythropoietin].
AB  - The sensibility to erythropoietin oferythroblastic islands of bone marrow which
      were made in different terms after the creation of transfusion polycytemia is
      researched. It turned out that the central macrophags of involuting
      erythroblastic islands are more sensible to erythropoietin than residual
      macrophags of bone marrow. The capability of residual macrophags to form
      erythroblastic islands is opened to the bigger inhibitory influence during the
      development of transfusion polycytemia than to the central macrjphags of
      involuting erythroblastic islands.

PMID- 20058818
TI  - [The investigation of dynamic changes of erythropoietin content of the
      erythroblast island cultures].
AB  - Dynamic changes of erythropoietin content on the 6th, 12th, 24 and 48th hours of
      cultivation in bone marrow erythropoietic island liquid short-term cultures were
      investigated. The initial doses of 0.25, 0.5, 1 mE/ml oferythropoietin was used,
      and one series with no erythropoietin as control. In culture with 0.25 mE/ml of
      erythropoietin, its reduction was registered from the 6th to 48th hours of
      cultivation with relatively lower number of erythroblast islands in state of
      involution, and a higher number in the state of reconstruction. In cultures with
      0.5 mE/ml oferythropoietin, the same erythropoietin reduction was registered with
      relatively higher numbers of erythroblast islands in the state of reconstruction,
      and with an unexpected elevation of erythropoietin concentration on the 48th hour
      of cultivation. In cultures with 1 mE/ml oferythropoietin, such unexpected rise
      in erythropoietin content was registered in 24 hours, accompanied by relatively
      higher number of erythroblast islands in the state of reconstruction.

PMID- 20058819
TI  - [Initiation of locomotion in decerebrated cat by using of impulse magnetic field
      projected onto the spinal cord segments].
AB  - The motor effects induced by impulse magnetic field (IMF) applied to lumbar as
      well as to cervical enlargements in decerebrated cat were studied. The magnetic
      coil with diameter 8 cm was placed on the distance 1-2 cm over the spinal cord.
      Single magnetic spinal cord stimulation with intensity 0.5-1 Tesla as well as
      continuous magnetic stimulation with frequency of 1 Hz and intensity 0.5 Tesla
      was performed. Single magnetic stimulation of lumbar enlargement elicited reflex
      responses in proximal and distal hind limb muscles. Continuous stimulation
      induced the locomotor activity in hind limbs on moving treadmill belt by
      activation of neuronal spinal locomotor networks (generator of stepping
      movements). The stimulation of lumbar enlargement involved into the locomotor
      activity only hind limbs. Continuous magnetic stimulation of cervical
      enlargerment evoked coordinated stepping movements in fore- and hind limbs.
      Initially stepping movements raised in hind limbs and then in forelimbs. After
      cessation of magnetic stimulation some coordinated stepping movements were
      observed. Thus, for the first time we showed a possibility to induce the
      locomotor activity in decerebrated cat by magnetic stimulation. The obtained
      results demonstrate the ability of non-invasive mode of neuronal spinal locomotor
      network activation. This approach opens new perspectives for using magnetic
      stimulation in clinical practice.

PMID- 20058820
TI  - [Participation of glucocorticoid hormones in gastroprotection during ischemia and
      ischemia-reperfusion in rats].
AB  - The investigation concerned glucocorticoid hormones participation in
      gastroprotection during ischemia and ischemia-reperfusion in rats. Gastric
      ischemia was performed by occlusion of celiac artery in anaesthetized rats. The
      stomach was exposed to brief ischemia as well as brief or prolonged ischemia
      reperfusion. Deficiency of glucocorticoid production (created by adrenalectomy or
      by metyrapone pretreatment) and occupation of glucocorticoid receptors by the
      antagonist RU-38486 were used to estimate the participation of glucocorticoids.
      Gastric ischemia and ischemia-reperfusion induced plasma corticosterone rise. The
      deficiency of corticosterone production as well as the occupation of
      glucocorticoid receptors resulted in aggravation of gastric mucosal damage
      produced by ischemia and ischemia-reperfusion. Thus, glucocorticoid hormones do
      participate in gastroprotection during ischemia and ischemia-reperfusion in rats.

PMID- 20058821
TI  - [Changes in the thyroid activity and influence of dehydroepiandrosterone-sulfate
      under the cold and not cold influence].
AB  - The dehydroepiandrosterone-sulfate (DHEAS) effect on thyroxine (T4) and
      triiodothyronine (T3) levels, after the multiple (for 19 days, 1 hr a day) cold
      (+4 degrees) or stress without cold factor (agitation of rats on the laboratory
      scrambler) and the possible participation of mu-opioid receptors in this DHEAS
      effect in male rats. It is shown that DHEAS (30 mg/kg) caused the additional
      increased T4 and T3 levels indicated the activation of thyroid system. Under
      multiple stress-factor, the expressed DHEAS-dependent activation of thyroid
      system, in contrast to the cold-factor, is observed not immediately after action,
      but only 30 and 120 min after its curtailment, but it is not revealed without
      DHEAS in the studied time interval. The introduction antagonist of opioid
      receptor antagonist naltrexone at the dose of 0.1 mg/kg, which it selectively
      blocks mu-opioid receptors, removes the additional thyroid activation effect of
      DHEAS, both in cold and in stress factor, indicating the realization in both
      cases of this DHEAS effect through the mu-opioid receptors, but under the stress
      factor but not cold influence the observed phenomenon is set aside time to 30, to
      120 min.

PMID- 20058822
TI  - [Action motor food of behaviour in modular device].
AB  - The technique for studying of the got behaviour at laboratory animals is offered.
      The corrective influence of high doses of Piracetam is shown on the example of
      aimed motor food runnings which contribute to food reguiments. Primary
      differences of the modular device in comparison with the "Colombian" chamber are
      noted.

PMID- 20058823
TI  - [The analysis of PPARGC1B gene polymorphism in athletes].
AB  - The aim of the study was to investigate allelic distribution of the peroxisome
      proliferator-activated receptor gamma coactivator 1beta gene (PPARGC1B; Ala203Pro
      polymorphism) in athletes (n = = 1535) and controls (n = 1113), and to find
      interrelation between genotypes and aerobic performance of athletes. Genotyping
      was performed by restriction of the fragment length polymorphism. Aerobic
      capacity was determined using incremental test to exhaustion by rower ergometer.
      The frequency of PPARGC1B 203Pro allele was significantly higher in endurance
      oriented athletes (n = 582; 7.2 %, p = 0.007), athletes with acyclic activity (n
      = 488; 8.1%, p = 0.0005), and power-oriented athletes (n = 372; 7.1%, p = 0.026)
      than in controls (4.9%), and it increased with the growth of skills (p = 0.046).
      Furthermore, we found that PPARGCIB 203Pro allele was associated with higher
      values of aerobic performance (when oxygen pulse and maximal power production
      capacity were measured). Thus, the PPARGC1B gene Ala203Pro polymorphism is
      associated with physical performance of athletes.

PMID- 20058824
TI  - [The effect of the "yellow" mutation at the mouse agouti locus on the hormonal
      profile of pregnancy and lactation].
AB  - The "yellow" mutation at the mouse agouti locus (A(y)/a-mice) results in obesity
      and type 2 diabetes. Maternal obesity in A(y)-mice impaired glucose tolerance in
      adult Agouti-negative offspring. Changes of hormone pattern during pregnancy and
      lactation are known to disregulate glucose metabolism in the adult progeny. The
      aim of the study was to assay blood levels of glucose, insulin, corticosterone
      and leptin during pregnancy (days 7, 13, 18) and lactation (days 1, 10, 21) in
      C57B1/6J mice of a/a (normal metabolism) and A(y)/a genotypes. A(y)/a-mice did
      not differ from a/a-mice in insulin and glucose levels during pregnancy and
      lactation, in corticosterone levels during pregnancy, but had higher leptin
      levels in pregnancy and lactation and increased corticosterone levels during
      lactation. A(y)/a-mice may be considered as a genetic model for studying impact
      of maternal leptin and corticosterone in developmental programming.

PMID- 20058825
TI  - [Age-related aspects of male reproductive function in rats with normal and
      accelerated senescence].
AB  - The study was performed on male rats with normal rate of aging (Wistar) and
      senescence-accelerated OXYS rats. Sexual motivation behaviour, activation of
      endocrine testicle function under condition of sexual activation, gravimetric
      rates were studied in male rats of different age. Potential ability to
      spermatogenesis in testis was studied in 14-month male rats. Males underwent the
      partition test: a receptive female was introduced into the male's cage, but the
      male and female were separated by a transparent partition. The number of
      approaches to the partition and total time spent near partition during the test
      served as an index of sexual motivation. Activation of hypothalamic-pituitary
      testicular complex was estimated by plasma testosterone level. A decrease of
      sexual motivation in the 14-month OXYS males was observed in comparison both with
      3- and 6-month OXYS rats and with 14-month Wistar rats. However, no decrease in
      hormonal component of sexual arousal in aged OXYS males rats was detected. No
      interstrain differences in potential ability to spermatogenesis in 14-month rats
      were observed. However, no interstrain differences in the weights of androgen
      dependent reproductive organs (testes and preputial glands) were observed under
      18-month age. However, the weight of epididymisis in 24-month OXYS rats was
      significantly smaller than in Wistar rats.

PMID- 20058826
TI  - [Effect of exogenous phosphatidylserine on cognitive function and hippocampus
      phospholipid turnover in old rats].
AB  - The aim of the research was to examine possible role of exogenous
      phosphatidylserine in the modulation of the phospholipid turnover in the
      hippocampus and cognitive function of old rats. It has been determined that
      phosphatidylserine content in the hippocampus of the old rats intragastrically
      fed with lipids increased up to the level of phosphatidylserine in the brain of
      young animals. The exogenous phosphatidylserine had no effect on the
      phosphatidylethanolamine turnover and increase phosphatidylcholine synthesis in
      the hippocampus of old rats. Cognitive function of lipid-fed and control 24-month
      old rats were studied with the aid of the active avoidance test in shuttle box.
      It has been determined that phosphatidylserine increased the number of active
      avoidances and decreased latency of active avoidance reaction in the learning
      session as compared with control rats.

PMID- 20058827
TI  - [Structural equation model for predicting well-being and functional dependency of
      the elderly in the Dominican Republic].
AB  - OBJECTIVE: To produce a multivariate structural model that explains functional
      dependence and well-being in terms of certain related sociodemographic factors
      among elderly adults in the Dominican Republic. METHODS: A cross-sectional study
      that surveyed a sample of 1,397 individuals 65 or more years of age, representing
      the Dominican Republic's elderly population. Those surveyed were asked for
      sociodemographic information (sex, age, level of education, employment status,
      and income level), data needed to determine their Barthel Index, and responses to
      questions from Ryff's Scale of Psychological Well-being. Three structural
      equation models were used to identify relationships among the key variables.
      RESULTS: The most fitting structural adjustment model linked sociodemographics to
      the ability to perform basic activities of daily living (BADL) and the Ryff's
      Scale of Psychological Well-being, without suggesting latent factors. With regard
      to endogenous variables, the model's predictive power was weak. Age was
      negatively associated with some areas of well-being and with the ability to
      perform BADL; sex was related to the area of positive relationships with others;
      and educational level positively influenced environment, personal growth, and
      having a sense of purpose, as well as the ability to perform BADL. CONCLUSIONS:
      The proven models provide information necessary for developing policies aimed at
      two levels of coordinated action: promoting autonomy among elderly adults and
      expanding enrollment in formal education programs. These results support efforts
      to increase investment in social policies.

PMID- 20058828
TI  - Maternal and congenital syphilis in rural Haiti.
AB  - OBJECTIVES: A study was conducted to assess the prevalence of maternal syphilis
      and estimate the rate of congenital syphilis in five rural villages surrounding
      Jeremie, Haiti. METHODS: This research was a retrospective observational study.
      Data were extracted from the Haitian Health Foundation's public health database
      and verified through original clinical paper records, death certificates, midwife
      reports, and discussions with community health workers. Data were analyzed by chi
      square analysis, bivariate correlations, and two-tailed t-test for independent
      samples. RESULTS: Of the 410 women tested for syphilis, 31 (7.6%) were sero
      reactive. Average gestation at time of testing was 25 weeks, which correlated
      with entry into prenatal care at an average of 23 weeks. Women who tested
      positive during pregnancy were more likely to have had a negative pregnancy
      outcome than those who did not (chi square = 16.4; P < 0.0001). The estimated
      rate of congenital syphilis in the region was 767 per 100,000 live births.
      CONCLUSIONS: Maternal syphilis is prevalent in rural Haiti. This prevalence
      combined with late entry into prenatal care contributes to adverse pregnancy
      outcomes and a high estimated rate of congenital syphilis. More research is
      needed on congenital syphilis and prenatal-careseeking practices of rural Haitian
      women in order to understand the impact of maternal syphilis in the region and
      improve pregnancy outcomes.

PMID- 20058829
TI  - [Impact of malaria during pregnancy in the Amazon region].
AB  - OBJECTIVE: To estimate the impact of malaria on the course of pregnancy in women
      from the Amazon region and to investigate possible risk factors in this
      population. METHODS: This cross-sectional study is part of a larger project to
      study malaria and pregnancy in the Amazon region. Pregnant women with malaria
      receiving care at the Amazon Tropical Medicine Foundation (Fundacao de Medicina
      Tropical do Amazonas) who answered a structured interview were included in the
      study. Socioeconomic, behavioral and clinical data were collected in the first
      consultation relating to each new malaria attack. All the women were followed-up
      throughout their pregnancy. The following risk factors for impact of malaria on
      the course of pregnancy were considered: being younger than 20 years of age,
      first pregnancy, first malaria infection, and type of infecting plasmodium
      species. RESULTS: Five hundred and thirty-five malaria episodes were evaluated in
      417 pregnant women, with 20.56% being caused by P. falciparum, 78.69% by P. vivax
      and 0.75% by the association of both parasites. Changes in the course of
      pregnancy were very frequent (26.2%). Threat of abortion was observed in 49 cases
      (25.5%), abortion in two (1.0%), threat of premature birth in 74 (25.1%), and
      premature birth in three (1.0%). First pregnancy and age < 20 years were
      significantly associated with threat of premature birth and abortion. CONCLUSION:
      Changes in the course of pregnancy were very frequent during acute malaria
      attacks, despite the low frequency of abortion. The present results do not
      highlight specific risk factors, suggesting that any pregnant woman may be at
      risk for the threat of abortion or for abortion during acute malaria attacks.

PMID- 20058830
TI  - [Sociodemographic factors associated with symptoms of depression in a sample
      women held at two prisons in Mexico].
AB  - OBJECTIVES: To determine the prevalence of depressive symptoms among a sample of
      women held in two Mexican prisons and to identify the sociodemographic factors
      associated with these symptoms. METHODS: An exploratory, descriptive study was
      conducted of women 18-50 years of age in two prisons in the state of Veracruz,
      Mexico: the Pacho Viejo (PV) facility and Fortaleza San Carlos (FSC) facility.
      The Hamilton scale for depressive illness was applied and relationships were
      found between the participants' scores and their sociodemographic traits (age,
      marital status, number of children, jail work assignment, and number/frequency of
      visitors), legal status, type of crime committed, and length of sentence. The
      analysis employed Student's T test, Chi-squared test, and Student-Newman-Keuls'
      post hoc test, depending on the variable. RESULTS: All of the women studied at
      both facilities presented with symptoms of depression. Women at the PV facility
      had a lower score for depressive symptoms than those at FSC (20.8 +/- 0.8 versus
      25.2 +/- 0.9; P <0.001). A higher score was found among women with children than
      among those without children (25.3 +/- 0.9 versus 21.8 +/- 1.3; P < 0.05); the
      group of women receiving weekly visits scored (15.0 +/- 1.3) significantly lower
      than the other groups (F[4.46] = 30.7; P < 0.0001). No significant differences
      were found to be related to marital status, work assignment, age, type of crime,
      or the length of sentence. CONCLUSIONS: Symptoms of depression were prevalent
      among the study sample, and were most powerfully related to having children and
      infrequent visits. Social adaptation programs should encourage continuous contact
      between women and their children, family, and friends.

PMID- 20058831
TI  - Prevalence of retinopathy of prematurity: an institutional cross-sectional study
      of preterm infants in Brazil.
AB  - OBJECTIVE: Retinopathy of prematurity (ROP) is the leading cause of childhood
      blindness in most developed countries. This study aimed to verify ROP prevalence
      among all very low birth weight (VLBW) preterm infants admitted to a level-3
      teaching hospital in Porto Alegre, Rio Grande do Sul, Brazil. METHODS:
      Institutional cross-sectional study of 407 premature infants with birth weight <
      or = 1,500 g or gestational age (GA) < or =32 weeks between 2002 and 2007. All
      infants screened for ROP were examined after the fourth week of life and followed
      up until the 45th week of adjusted GA. ROP prevalence was estimated at a 95%
      confidence level. RESULTS: Some degree of ROP in one or both eyes occurred in
      25.5% (104) of all screened infants, and severe ROP (threshold stage 3 or higher,
      requiring treatment to prevent vision loss, as per the criteria of the U.S.-based
      Multicenter Trial of Cryotherapy for Retinopathy of Prematurity, CRYO-ROP)
      occurred in 5.8% (24). Based on the criteria of The International Classification
      for Retinopathy of Prematurity (ICROP, 1984/1987), the disease reached stages 1,
      2, and 3 in 11.3% (46), 8.4% (34), and 5.4% (22), respectively. One infant
      developed the disease up to stage 4 (partial retinal detachment), and one
      progressed to stage 5 (complete retinal detachment, resulting in 0.2% overall
      prevalence for ROP-induced blindness). CONCLUSIONS: Overall incidence of ROP in
      this institutional study (25.5%) was comparable to international results from
      developed countries. A comprehensive countrywide survey on ROP in Brazil is
      recommended to determine any regional differences in disease prevalence.

PMID- 20058832
TI  - Risk factors for pregnancy among adolescent girls in Ecuador's Amazon basin: a
      case-control study.
AB  - OBJECTIVE: To examine risk factors for pregnancy among adolescent girls in the
      Amazon basin of Ecuador. METHODS: A matched case-control study with cases and
      controls identified within a community-based demographic and health survey was
      conducted in Orellana, Ecuador, from May to November 2006. A questionnaire
      focused on socioeconomic status, family structure, education, reproductive
      health, and childhood-adolescent trauma was applied. Conditional logistic
      regression was used to adjust for potential confounders. RESULTS: Respondents
      included 140 cases and 262 controls. Factors associated with increased risk of
      adolescent pregnancies through multivariate analysis were: sexual abuse during
      childhood-adolescence (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.08
      8.68); early sexual debut (OR 8.51, 95% CI 1.12-64.90); experiencing periods
      without mother and father (OR 10.67, 95% CI 2.67-42.63); and living in a very
      poor household (OR 15.23, 95% CI 1.43-162.45). Another two factors were
      statistically associated in the bivariate analysis: being married or in a
      consensual union (OR 44.34, 95% CI 17.85-142.16) and not being enrolled in school
      at the time of the interview (OR 6.31, 95% CI 3.70-11.27). For a subsample of
      sexually initiated adolescents, "non-use of contraception during first sexual
      intercourse" was also found to be a risk factor (OR 4.30, 95% CI 1.33-13.90).
      CONCLUSION: The study found that early sexual debut, non-use of contraception
      during first sexual intercourse, living in a very poor household, having suffered
      from sexual abuse during childhood-adolescence, and family disruption (living
      extended periods of life without both parents) were associated with adolescent
      pregnancy in Orellana.

PMID- 20058833
TI  - [Assessing the insecticide resistance of an Aedes aegypti strain in El Salvador].
AB  - OBJECTIVES: To assess the level of insecticide susceptibility of a certain Aedes
      aegypti strain found in El Salvador and to explain the mechanisms for its
      resistance to temephos. METHODS: An A. aegypti strain from the municipality of
      Soyapango, Department of San Salvador, El Salvador, was studied. Bioassays were
      used to determine the susceptibility of the larvae to the organophosphate
      insecticide temephos and to three pyrethroids (deltamethrin, lambda-cyhalothrin,
      and cypermethrin); and of adults to an organophosphate insecticide
      (chlorpyrifos). The resistance factor (RF50) with determined with respect to a
      reference susceptible strain (Rockefeller). The mechanism of temephos resistance
      was determined through the use of synergistic substances, biochemical assays for
      enzymatic activity, and polyacrylamide gel zymograms. RESULTS: The larvae of the
      strain studied proved highly resistant to temephos (RF50 = 24.16). Of the enzyme
      samples analyzed, only the esterase A4 was linked to the mechanism of temephos
      resistance. The adult mosquitoes were susceptible to lambda-cyhalothrin and
      chlorpyrifos; and resistance to deltamethrin and cypermethrin fell into the
      category needing further verification. CONCLUSIONS: Temephos resistance could
      reduce the efficiency of chemical control of the A. aegypti mosquito in El
      Salvador study area. Chlorpyrifos, lambda-cyhalothrin, and cypermethrin are good
      alternative insecticides for use in new efforts to control this vector.

PMID- 20058834
TI  - Work-related injuries among child street-laborers in Latin America: prevalence
      and predictors.
AB  - OBJECTIVES: To determine the prevalence and nature of occupational injuries among
      children working in the streets of four major cities in Latin America, as well as
      to identify factors that predict these work-related injuries. METHODS: This cross
      sectional study interviewed 584 children from 5-17 years of age working on the
      streets of Bogota, Colombia; Lima, Peru; Quito, Ecuador; and Sao Paulo, Brazil.
      Descriptive analyses and multivariate logistic regressions were conducted, with
      incidence and serious injuries regressed on occupational and sociodemographic
      variables. RESULTS: Approximately 39.6% of the child street-laborers surveyed
      reported an injury sustained while working in the streets: scratches (19.5%),
      cuts/lacerations (16.4%), burns (8.6%), car accidents (8.9%), sprains (4.6%), and
      amputations (0.3%). Working a high number of daytime hours and performing on the
      street predicted the greatest risk of injury, even after controlling for
      sociodemographic factors; specifically, each additional hour of daytime work
      increased the risk of injury by 1.4%. Child performers had three times the injury
      rate of children primarily selling products. Boys, older children, and children
      in Quito were more likely to experience moderate-to-severe injuries, than girls,
      younger children, and street children in the other study cities. CONCLUSIONS:
      Interventions are needed to address the substantial risk of injury experienced by
      children working on the city streets of Latin America.

PMID- 20058835
TI  - [Reasons for and barriers to exercising and sports participation in Madrid].
AB  - OBJECTIVES: To analyze the motivators and barriers to physical activity and
      sports among the population of metropolitan Madrid, as well as any correlations
      with gender, age, and social status. METHODS: A cross-sectional study of a sample
      of 625 individuals whose data were representative of the whole population, with a
      +/- 4% margin of error and a 95.5% confidence interval (95%CI). The sampling type
      selected was multistage, utilizing an ad hoc questionnaire. RESULTS: The most
      frequently cited motivations for exercising were: for fun (29.9%), to stay in
      shape (26.4%), and health (16.1%), differing according to gender (chi2(8) =
      19.635; P = 0.009; 95%CI: 0.007-0.011) and age (chi2(32) = 55.671; P = 0.006;
      95%CI: 0.005-0.0080). With regard to activity cessation, the demands of work and
      family (24.1%) and lack of time (22.2%) were the most common reasons, correlating
      with age (chi2(24) = 36.955; P = 0.041; 95%CI: 0.037-0.044) and slightly with
      gender (chi2(6) = 11.753; P = 0.069; 95%CI: 0.063-0.074). The reasons most often
      cited for never exercising were lack of time (24.4%) and not enjoying it (24.4%),
      uncorrelated with any of the study variables. CONCLUSIONS: Among the study
      sample, the purpose of sports and exercise was for fun and recreation, aimed at
      maintaining and improving health and acquiring an attractive figure. Motivators
      driving activity and discontinuation were correlated with age and gender.
      Conversely, the reasons for never exercising were independent of the study
      variables.

PMID- 20058836
TI  - Monetary valuation of illnesses in Costa Rica: a subjective well-being approach.
AB  - OBJECTIVE: This report aims to 1) explain and illustrate the use of the
      subjective well-being (SWB) approach as an alternative health-valuation
      methodology by estimating the monetary value of five general categories of
      illness in Costa Rica, and 2) foster comparative research on the advantages and
      limitations of alternative approaches to health valuation. METHOD: Use of the SWB
      valuation approach to measure the monetary value of illness (MVI), based on
      empirical data from a representative survey in Costa Rica carried out in 2004.
      The MVI is defined as the estimated percentage of monthly income that would be
      required to compensate for the loss in life satisfaction (LS)--a primary SWB
      conception-that is expected to occur with the onset of illness. The five general
      categories of illnesses studied were cancer, cardiovascular disease, thyroid
      disease, arthritis, and infectious disease. RESULTS: There was wide disparity in
      the monetary values of the different illnesses. Some illnesses had relatively
      high monetary value compared to persons' mean income, indicating the high value
      of good health and of programs that aim to prevent the emergence of illnesses or
      abate their negative impact on people's well-being. CONCLUSIONS: The SWB
      valuation approach can be used to estimate illnesses' monetary value and thus can
      contribute to the design of health policies related to resource allocation and
      compensation, and revenue-generating schemes.

PMID- 20058837
TI  - Neurotoxicity and aggressiveness triggered by low-level lead in children: a
      review.
AB  - Lead-induced neurotoxicity acquired by low-level long-term exposure has special
      relevance for children. A plethora of recent reports has demonstrated a direct
      link between low-level lead exposure and deficits in the neurobehavioral
      cognitive performance manifested from childhood through adolescence. In many
      studies, aggressiveness and delinquency have also been suggested as symptoms of
      lead poisoning. Several environmental, occupational and domestic sources of
      contaminant lead and consequent health risks are largely identified and
      understood, but the occurrences of lead poisoning remain numerous. There is an
      urgent need for public health policies to prevent lead poisoning so as to reduce
      individual and societal damages and losses. In this paper we describe unsuspected
      sources of contaminant lead, discuss the economic losses and urban violence
      possibly associated with lead contamination and review the molecular basis of
      lead-induced neurotoxicity, emphasizing its effects on the social behavior,
      delinquency and IQ of children and adolescents.

PMID- 20058838
TI  - [Human resources for health in Chile: the reform's pending challenge].
AB  - Omission of human resources from health policy development has been identified as
      a barrier in the health sector reform's adoption phase. Since 2002, Chile's
      health care system has been undergoing a transformation based on the principles
      of health as a human right, equity, solidarity, efficiency, and social
      participation. While the reform has set forth the redefinition of the medical
      professions, continuing education, scheduled accreditation, and the introduction
      of career development incentives, it has not considered management options
      tailored to the new setting, a human resources strategy that has the consensus of
      key players and sector policy, or a process for understanding the needs of health
      care staff and professionals. However, there is still time to undo the
      shortcomings, in large part because the reform's implementation phase only
      recently has begun. Overcoming this challenge is in the hands of the experts
      charged with designing public health strategies and policies.

PMID- 20058839
TI  - [Granulocyte colony stimulating factor in the ambulatory treatment of neutropenia
      following chemotherapy].

PMID- 20058840
TI  - [Forensic medical reconstruction of the mechanism of subdural hematoma
      development following multiple head injury].
AB  - This paper presents results of 103 observations of subdural hematomas (SH)
      resulting from the injury to extradural segments of cerebral veins. A
      craniocerebral trauma was shown to effect the frequency of development and
      localization of subdural hemorrhage. Individual head tissues exhibited different
      degree of resistance to mechanical injury. This observation was used to evaluate
      the probability of overcoming the threshold of their mechanical tolerance
      necessary for the induction of SH of cerebrovenous origin. The analytical
      technology is proposed for forensic medical reconstruction of the mechanism of
      development of subdural hematomas following multiple head injury. It is concluded
      that the results of the study can be used for the purposes of practical forensic
      medical examination.

PMID- 20058841
TI  - [Identification of male somatotype based on osteometric characteristics of the
      upper and lower extremities].
AB  - This osteologic study included examination of 101 skeletons from the collections
      of the Department of Anthropology, M. V. Lomonosov Moscow State University, and
      Peter the Great Museum of Anthropology and Ethnography (Sankt-Peterburg). The
      results were compared with the data obtained by examining materials excavated
      from grave sites of an Yoshkar-Ola cemetery and from the Isupovo necropole
      (Kostroma) to evaluate the possibility of identifying human somatotypes from bone
      remains. Multidimensional discriminative analysis demonstrated that the equation
      derived by comparing characteristic signs of all long tubular bones of the
      extremities was of highest diagnostic value for the purpose of the study.
      Diagnostic equations are proposed for the identification of individual
      somatotypes based on the analysis of skeletal remains for the use in practical
      forensic medical examination.

PMID- 20058842
TI  - [Specific features of digital dermatoglyphics in the population of the Tiumen'
      region].
AB  - Fingerprints of all wrist phalanges were obtained from Russian residents of the
      Tyumen region (150 men and 150 women). Distal phalange dactylograms showed all
      types of fingerprint patterns, such as loops, whorls and arches. Ulnar loops and
      whorls predominated over other varieties whereas arches and radial loops were
      relatively rare. Middle and proximal phalanges also exhibited a large variety of
      fingerprint patterns that occurred with different frequency. Marked gender
      related and bilateral differences in the fingerprint patterns were documented. It
      is concluded that considerable variability of wrist phalange dermatoglyphics in
      the population group included in the study confirms the necessity of more
      extensive use of these data in forensic medical examination for the purpose of
      personality identification.

PMID- 20058843
TI  - [Optimization of methods for DNA extraction from objects of forensic medical
      examination].
AB  - An optimized method for DNA extraction from materials available for forensic
      medical examination is proposed based on partial combination of two procedures,
      phenol-chloroform extraction and sorption. Such a combination provided a basis
      for the development of a protocol making use of the advantages of both procedures
      and free of drawbacks of either of them. This relatively simple and rapid method
      uses no reagents having adverse effect on human organism. Also, it excludes the
      use of substances interfering with polymerase chain reaction (PCR) and thereby
      reduces the risk of DNA loss. This makes it suitable for the work with objects
      having very low DNA content. The DNA specimens obtained with the help of the
      proposed technique are fit for prolonged storage.

PMID- 20058844
TI  - [Detection of rhesus D-antigen in mixed traces of blood and excretions].
AB  - The objective of this study was to evaluate the possibility of detecting rhesus D
      antigen in mixed traces of blood and excreta with the use of anti-D peptides. The
      described absorption-elution procedure allows for the identification and
      measurement of D-antigen in mixed samples of blood and excreta due to specific
      serological properties of anti-D peptides that make them more suitable for the
      purpose compared with native polyclonal anti-D antibodies. The new immunological
      method is the first one to be used in forensic medicine for distinguishing blood
      Rh-antigens (e.g. D-antigen) present in mixed traces of blood and excreta. Hence,
      its high practical value.

PMID- 20058845
TI  - [Evaluation of toxicological situation in a fire and its effect on the results of
      forensic medical examination].
AB  - Analysis of regulatory requirements pertaining to toxicological safety of people
      during fires is presented along with the most important factors responsible for
      aggravated toxicological situation unspecified in these documents. The necessity
      to further extend the database on fire-specific factors and production of highly
      toxic gases is emphasized. The close relationship between variations of fire
      related threats to the human health and results of relevant forensic medical
      examination is demonstrated.

PMID- 20058846
TI  - [Ethanol elimination rate (beta60, beta-slope) in different age groups after
      intake of a moderate or high dose of alcohol].
AB  - Ethanol elimination rate (beta60) was measured in different age groups of men and
      women following its single intake at a dose of 0.8 g/kg body weight (experiment
      1) and 2 g/kg (experiment 2). Samples of capillary blood were collected 20, 40,
      60, 90, 120, and 300 min (experiment 1) or 360 min after the termination of the
      intake (experiment 2). The phase of alcohol elimination was deduced from the
      kinetic curve. Each alcohol dose was consumed during 1-2 minutes or 1-1.5 hours
      (experiments 1 and 2 respectively). The value of (beta60) in experiment 1 was
      estimated at 0.17 +/- 0.04 per thousand/hour in young men aged between 18-26
      years, 0.22 per thousand/hour in adult men of 32-48 years, and 0.21 per
      thousand/hour in women aged between 19-41 years. The difference between alcohol
      elimination rates in young and adult men on the one hand and between young men
      and women on the other hand was statistically significant (p < 0.01 and p < 0.05
      respectively). In the second experiment, ethanol elimination rate was practically
      identical in men of the above age groups (0.16 +/- 0. 02 per thousand/hour) and
      significantly higher than in 64-66 year-old men (0.14 +/- 0.03 per
      thousand/hour). The values of ethanol elimination rate in men of group 2
      calculated by the Weedmark formula proved underestimated by 17 +/- 5% regardless
      of their age. Men of both age groups included in experiment 1 showed an alcohol
      excretion rate overestimated by 8 +/- 5% and 31 +/- 6% respectively compared with
      10 +/- 7% in women. It is suggested that a single intake of alcohol may lead to
      an instantaneous rise in the hepatic concentration of ethanol unrelated to the
      consumed amount that however affects its metabolic rate. It is concluded that the
      duration of ethanol intake has greater effect on the rate of its elimination from
      the body than the amount of consumed alcohol, especially in alcohol-tolerant
      subjects.

PMID- 20058847
TI  - [Detection of selected diuretics in biological fluids by chromatography mass
      spectrometry].
AB  - Modified methods for the detection and measurement of furosemide and
      spironolactone in biological fluids has been developed based on gas
      chromatography mass spectrometry. Optimal conditions for chromatography are
      described for the determination of the diuretic agents of interest. The proposed
      methods were verified by analysing urine samples obtained from patients with
      chronic cardiac insufficiency.

PMID- 20058848
TI  - [Detection of bensultap (bancol) derivatives and metabolites by chromatographic
      methods].
AB  - This paper is designed to describe methods for the detection of derivatives and
      metabolites of the insecticidic agent bancol (nereistoxin precursor) by
      chromatographic methods including thin layer chromatography (TLC), high
      performance liquid chromatography (HPLC), gas chromatography with a nitrogen
      phosphorous detector (GC-NPD), and gas chromatography mass spectrometry (GH-MS).
      The data obtained confirm the high diagnostic value of assays for derivatives and
      metabolites compared with the determination of the respective parent
      insecticides. New variants of extraction of these compounds from urine and
      various tissues by liquid-liquid and solid-phase chromatography are proposed.
      Their spectral and chromatographic characteristics are reported.

PMID- 20058849
TI  - [An example of situational expertise in the analysis of radiation-induced
      injury].

PMID- 20058850
TI  - [Fatal poisoning with the local anesthetic bupivacaine].
AB  - Lethal concentration of bupivacaine was determined based on the examination of a
      case of poisoning with this local anesthetic agent taken at a dose 5 times the
      normal value. This study is of special interest taking into consideration the
      lack of data on toxic and lethal doses of bupivacaine in splanchnic organs and
      tissues in the literature.

PMID- 20058851
TI  - [An overview of forensic medicine dissertations studying forensic biology
      problems published in Russia].
AB  - The objective of this work was to analyse the subject matter and relative number
      of dissertations devoted to different aspects of forensic biology published
      during consecutive decades throughout a long period from 1894 to 2009. The main
      lines of research carried out during this time are specified. Alternation of
      increasing and decreasing trends in the number of thesis works is revealed. Taken
      together and categorized in terms of its character, this information on
      dissertations concerned with the subject of forensic biology may prove helpful
      for current and prospective planning of research on the identification of
      material evidence.

PMID- 20058852
TI  - [On the history of foundation of the Russian Society of Forensic Medicine].
AB  - This analysis of archive documents has revealed unknown facts from the history of
      the single professional association of forensic medical examiners that existed in
      the pre-revolutionary Russia. Special attention is given to the contribution made
      by specialists based at Sankt-Peterburg to the foundation of the Russian Society
      of Forensic Medicine.

PMID- 20058853
TI  - HAGE, a cancer/testis antigen expressed at the protein level in a variety of
      cancers.
AB  - The search for novel tumour antigens that are either uniquely expressed or over
      expressed in a wide variety of tumours is still ongoing. Because of their
      expression in a broad spectrum of cancers and limited expression in normal
      tissues, cancer/testis antigens are considered to be potentially reliable targets
      for immunotherapy of cancer in general. The helicase antigen HAGE has been
      identified as a cancer/testis antigen. However, little is known about its
      expression in normal and cancer tissues. Using a newly developed antibody against
      HAGE, specific staining of its expression by immunohistochemistry was validated
      and optimised on murine tumours transfected to express the HAGE protein. The
      antibody was subsequently used to determine HAGE expression in normal human and
      cancer tissue microarrays. HAGE protein expression was confirmed in 75% (12/16)
      of carcinomas as compared to normal tissues, which either did not express HAGE at
      all or expressed HAGE at very low levels with the exception of testis.
      Interestingly, discrepancies were also found between mRNA analysis by real time
      quantitative PCR (RT-qPCR) and protein analysis by immunohistochemistry,
      emphasising the need to validate the expression of cancer/testis antigens at the
      protein level prior to the development of new vaccine strategies. HAGE is
      therefore proposed to be a valid candidate for designing a broad spectrum vaccine
      against cancer.

PMID- 20058855
TI  - Regulated attachment method for reconstituting lipid bilayers of prescribed size
      within flexible substrates.
AB  - A new method called the regulated attachment method (RAM) for reproducibly
      forming lipid bilayers within flexible substrates has been developed that enables
      precise control over the size of the bilayer. This technique uses a deformable
      flexible substrate to open and close an aperture that subdivides aqueous volumes
      submersed in an organic solvent. Phospholipids incorporated as vesicles in the
      aqueous phase self-assemble at the oil/water interface to form lipid monolayers
      that encapsulate each aqueous volume. Controlled attachment of opposing lipid
      monolayers is achieved by regulating the dimensions of the aperture in the
      substrate that separates the adjacent aqueous volumes. In this manner, the size
      of a lipid bilayer formed within a flexible substrate is a function of the
      substrate and aperture dimensions, and not determined by the sizes or shapes of
      the aqueous volumes. Lipid bilayers formed within the prototype flexible
      substrate exhibit DC resistances consistently higher than 10 GOmega and can
      survive 20-30x changes in area without rupture. Furthermore, RAM permits lipid
      bilayers to be completely unzipped after thinning by applying sufficient force to
      fully close the dividing aperture and even allows the introduction of species,
      such as alamethicin channels, into preformed lipid bilayers via controlled
      injection through an intersecting channel within the substrate. Controlling the
      size of the interface through indirect interactions with the supporting substrate
      offers a new platform for assembling durable lipid bilayers. We envision that
      this technology can be scaled to higher dimensions consisting of multiple
      apertures required for creating aqueous networks partitioned by functional lipid
      bilayers and to smaller length scales to produce very small lipid bilayers
      capable of hosting single proteins.

PMID- 20058856
TI  - Alignment-free ultra-high-throughput comparison of druggable protein-ligand
      binding sites.
AB  - Inferring the biological function of a protein from its three-dimensional
      structure as well as explaining why a drug may bind to various targets is of
      crucial importance to modern drug discovery. Here we present a generic 4833
      integer vector describing druggable protein-ligand binding sites that can be
      applied to any protein and any binding cavity. The fingerprint registers counts
      of pharmacophoric triplets from the Calpha atomic coordinates of binding-site
      lining residues. Starting from a customized data set of diverse protein-ligand
      binding site pairs, the most appropriate metric and a similarity threshold could
      be defined for similar binding sites. The method (FuzCav) has been used in
      various scenarios: (i) screening a collection of 6000 binding sites for
      similarity to different queries; (ii) classifying protein families (serine
      endopeptidases, protein kinases) by binding site diversity; (iii) discriminating
      adenine-binding cavities from decoys. The fingerprint generation and comparison
      supports ultra-high throughput (ca. 1000 measures/s), does not require prior
      alignment of protein binding sites, and is able to detect local similarity among
      subpockets. It is thus particularly well suited to the functional annotation of
      novel genomic structures with low sequence identity to known X-ray templates.

PMID- 20058854
TI  - Biochemical characterization of native Usher protein complexes from a vesicular
      subfraction of tracheal epithelial cells.
AB  - Usher syndrome is the major cause of deaf/blindness in the world. It is a genetic
      heterogeneous disorder, with nine genes already identified as causative for the
      disease. We noted expression of all known Usher proteins in bovine tracheal
      epithelial cells and exploited this system for large-scale biochemical analysis
      of Usher protein complexes. The dissected epithelia were homogenized in
      nondetergent buffer and sedimented on sucrose gradients. At least two complexes
      were evident after the first gradient: one formed by specific isoforms of CDH23,
      PCDH15, and VLGR-1 and a different one at the top of the gradient that included
      all of the Usher proteins and rab5, a transport vesicle marker. TEM analysis of
      these top fractions found them enriched in 100-200 nm vesicles, confirming a
      vesicular association of the Usher complex(es). Immunoisolation of these vesicles
      confirmed some of the associations already predicted and identified novel
      interactions. When the vesicles are lysed in the presence of phenylbutyrate, most
      of the Usher proteins cosediment into the gradient at a sedimentation coefficient
      of approximately 50 S, correlating with a predicted molecular mass of 2 x 10(6)
      Da. Although it is still unclear whether there is only one complex or several
      independent complexes that are trafficked within distinct vesicular pools, this
      work shows for the first time that native Usher protein complexes occur in vivo.
      This complex(es) is present primarily in transport vesicles at the apical pole of
      tracheal epithelial cells, predicting that Usher proteins may be directionally
      transported as complexes in hair cells and photoreceptors.

PMID- 20058857
TI  - Impact of point-source pollution on phosphorus and nitrogen cycling in stream-bed
      sediments.
AB  - Diffusive equilibration in thin films was used to study the cycling of phosphorus
      and nitrogen at the sediment-water interface in situ and with minimal disturbance
      to redox conditions. Soluble reactive phosphate (SRP), nitrate, nitrite,
      ammonium, sulfate, iron, and manganese profiles were measured in a rural stream,
      12 m upstream, adjacent to, and 8 m downstream of a septic tank discharge. Sewage
      fungus adjacent to the discharge resulted in anoxic conditions directly above the
      sediment. SRP and ammonium increased with depth through the fungus layer to
      environmentally significant concentrations (440 and 1800 microM, respectively)
      due to release at the sediment surface. This compared to only 0.8 microM of SRP
      and 2.0 microM of ammonium in the water column upstream of the discharge.
      Concomitant removal of ammonium, nitrite and nitrate within 0.5 cm below the
      fungus-water interface provided evidence for anaerobic ammonium oxidation
      (anammox). "Hotspots" of porewater SRP (up to 350 microM) at the downstream site
      demonstrated potential in-stream storage of the elevated P concentrations from
      the effluent. These results provide direct in situ evidence of phosphorus and
      nitrogen release from river-bed sediments under anoxic conditions created by
      sewage-fungus, and highlight the wider importance of redox conditions and rural
      point sources on in-stream nutrient cycling.

PMID- 20058858
TI  - Presentation of membrane-anchored glycosphingolipids determined from molecular
      dynamics simulations and NMR paramagnetic relaxation rate enhancement.
AB  - Challenges for structural characterization of membrane-bound glycosphingolipids
      include their high internal dynamic motions and their physical proximity to
      membrane surfaces. Here we demonstrate that NMR paramagnetic relaxation
      enhancement can be used, alongside independent molecular dynamics simulations and
      an outer-sphere relaxation model, to quantitatively characterize the presentation
      (insertion depth and orientation relative to a membrane surface) of ganglioside
      GM1 in biologically relevant membrane environments. Longitudinal and transverse
      paramagnetic relaxation enhancement effects were measured for GM1, anchored to
      phospholipid bicelles, using both water-soluble and membrane-anchored
      paramagnetic probes, respectively. A method was developed to rapidly calculate
      paramagnetic relaxation enhancement effects from thousands of structures taken
      from a simulation of GM1 in a phospholipid bilayer. The combined computational
      and experimental approach yielded experimentally verified atomic-resolution 3D
      models of a highly plastic membrane-bound biomolecule.

PMID- 20058859
TI  - Cooperative metal ion binding to a cucurbit[7]uril-thioflavin T complex:
      demonstration of a stimulus-responsive fluorescent supramolecular capsule.
AB  - We report an intriguing noncovalent interaction of thioflavin T (ThT), a fibril
      diagnostic dye, with the versatile macrocyclic host molecule cucurbit[7]uril
      (CB7) in the presence of metal cations. ThT forms both 1:1 (CB7.ThT) and 2:1
      [(CB7)(2).ThT] complexes with CB7 host, leading to specific structural
      arrangements. Addition of competitive guests like metal cations to the 1:1
      stoichiometric complex displays expected competitive binding interactions with
      CB7, leading to decreased fluorescence intensity from ThT. However, addition of
      metal ions to the 2:1 complex leads to unusual enhancement in the fluorescence
      emission ( approximately 270-fold in the presence of Ca(2+) and approximately 160
      fold in the presence of Na(+)). These contrasting observations on the
      fluorescence enhancement with change in the stoichiometric equilibrium have been
      investigated explicitly for a feasible binding model. Detailed photophysical
      characterization with supporting data from NMR and anisotropy measurements has
      led to the revelation of a novel stimulus-responsive cooperative metal ion
      binding to the stoichiometrically selected (CB7)(2).ThT complex, demonstrating a
      highly fluorescent supramolecular nanocapsule. The first example of a
      noncovalently packed fluorescent complex became feasible due to the structural
      arrangement of the host-guest complex in the 2:1 stoichiometry with two CB7
      portals providing strong negative charge density for the metal ions to group and
      seal the complex, thus protecting the incorporated dye. To further strengthen the
      usefulness of the supramolecular capsule established here, rupture of the
      capsular complex has been demonstrated with a strong competitive guest, 1
      amantadine hydrochloride, which helped in disrupting the capsule to release the
      dye. It is proposed here that by judicious design of the chromophore (guest)
      structure, such capsular assemblies can be explored for the binding and release
      of drug molecules, for fluorescence on-off systems, and as building blocks for
      molecular architectures displaying unique properties.

PMID- 20058861
TI  - Selective assembly of a high stability AAB collagen heterotrimer.
AB  - How collagen is able to obtain control of helix composition and register is
      poorly understood yet is critical for determining the structure and properties of
      the most abundant protein in the human body. In humans there are 28 known types
      of collagen that can form homotrimeric (AAA) or heterotrimeric (AAB and ABC)
      compositions. Additionally, because of a single amino acid offset between peptide
      chains in the triple helix, distinct heterotrimers of different registers can be
      formed. In this communication we describe an AAB collagen heterotrimer with
      controlled composition and register. This is the first report of a collagen
      heterotrimer whose thermal stability is greater than that of any of its component
      parts and therefore is the dominant species in solution. The design concept is
      simple: combination of peptides who follow the canonical (X-Y-Gly)(n) amino acid
      repeat in a 2:1 ratio in which the more abundant peptide has a charge 1/2 and
      opposite of the other should result in the formation of an AAB heterotrimeric
      collagen helix. This will be the dominant species because it is neutral
      (zwitterionic) while homotrimers should be destabilized because of charge
      repulsion. Here we show by circular dichroism, differential scanning calorimetry,
      and NMR that, in a 2:1 mixture of the peptides (EOGPOG)(5) and (PRG)(10), the AAB
      heterotrimer is the dominant structure in solution and melts 10 degrees C higher
      in temperature than the next most stable species.

PMID- 20058862
TI  - On the binding of cationic, water-soluble conjugated polymers to DNA:
      electrostatic and hydrophobic interactions.
AB  - Water-soluble, cationic conjugated polymer binds single-stranded DNA with higher
      affinity than it binds double-stranded or otherwise "folded" DNA. This stronger
      binding results from the greater hydrophobicity of single-stranded DNA. Upon
      reducing the strength of the hydrophobic interactions, the electrostatic
      attraction becomes the important interaction that regulates the binding between
      the water-soluble conjugated polymer and DNA. The different affinities between
      the cationic conjugated polymer and various forms of DNA (molecular beacons and
      its open state; single-stranded DNA and double-stranded DNA and single-stranded
      DNA and complex DNA folds) can be used to design a variety of biosensors.

PMID- 20058863
TI  - Predicting sediment sorption coefficients for linear alkylbenzenesulfonate
      congeners from polyacrylate-water partition coefficients at different salinities.
AB  - The effect of the molecular structure and the salinity on the sorption of the
      anionic surfactant linear alkylbenzenesulfonate (LAS) to marine sediment has been
      studied. The analysis of several individual LAS congeners in seawater and of one
      specific LAS congener at different dilutions of seawater was carried out after
      extraction by polyacrylate solid-phase microextraction (SPME) fibers. Sorption
      isotherms for the tested LAS congeners on marine sediment and at different ionic
      composition were all nonlinear with a constant Freundlich exponent (n(F)) of 0.78
      +/- 0.05. Differences in LAS sorption of a number of congeners were similar to
      the differences among the linear partition coefficients (K(fw)) observed for the
      polyacrylate SPME fibers in seawater. The sorption of LAS to both the sediment
      and the SPME fiber significantly decreased in media with lower salinity.
      Dissolved calcium could fully account for the changed affinity of LAS for the
      SPME fiber, although the high sorption in seawater was also equaled by a
      corresponding dissolved concentration of NaCl only. Sediment sorption
      coefficients of a single LAS congener at varying ionic composition was not as
      strongly related to the K(fw) values as the relation observed for different LAS
      compounds in seawater, likely because sorption mechanisms are different in both
      phases. In the absence of experimental data for octanol-water coefficients
      (K(ow)) of (i) individual LAS congeners at (ii) different ionic compositions, the
      use of K(fw) as a tool to predict sorption and other hydrophobicity-related
      processes is suggested.

PMID- 20058864
TI  - Long-term effects of three commercial cranberry products on the antioxidative
      status in rats: a pilot study.
AB  - Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used
      for their antiadherence and antioxidative properties. Little is known however
      about their effects on clinical chemistry markers after long-term consumption.
      This study was conducted to evaluate the effect of three commercial cranberry
      products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of
      rodents, divided into three experimental groups. The products were given as
      dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male
      Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed.
      There were no significant cranberry treatment-related effects on oxidative stress
      parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione
      transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric
      acid reactive substances, advanced oxidation protein products, total SH-groups,
      or any other measured clinical chemistry markers. Hematological parameters, body
      weight, and food consumption were also unaffected by intake of cranberries. Only
      liver glutathione reductase activity and glutathione levels were significantly
      lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was
      significantly decreased in Group 2. No gross pathology, effects on organ weights,
      or histopathology were observed. No genotoxicity was found, and total cytochrome
      P450 level in liver was unaffected in all groups. The levels of hippuric acid and
      several phenolic acids were significantly increased in plasma and urine in Groups
      2-4. The concentration of anthocyanins was under the detection threshold. The
      dietary addition of cranberry powders for 14 weeks was well tolerated, but it did
      not improve the antioxidative status in rats.

PMID- 20058865
TI  - Inhibitors of prolyl oligopeptidases for the therapy of human diseases: defining
      diseases and inhibitors.

PMID- 20058866
TI  - Proteome mining of human follicular fluid reveals a crucial role of complement
      cascade and key biological pathways in women undergoing in vitro fertilization.
AB  - In vitro fertilization (IVF) is fraught with problems and currently proteomics
      approaches are being tried out to examine the microenvironment of the follicle in
      order to assess biological and immunological parameters that may affect its
      development. Additionally, better understanding of reproductive process may help
      increase IVF birth rate per embryo transfer and at the same time avoid
      spontaneous miscarriages or life threatening conditions such as ovarian
      hyperstimulation syndrome. The primary aim of this study was to search for
      specific differences in protein composition of human follicular fluid (HFF) and
      plasma in order to identify proteins that accumulate or are absent in HFF.
      Depletion of abundant proteins combined with multidimensional protein
      fractionation allowed the study of middle- and lower-abundance proteins. Paired
      comparison study examining HFF with plasma/serum from women undergoing successful
      IVF revealed important differences in the protein composition which may improve
      our knowledge of the follicular microenvironment and its biological role. This
      study showed involvement of innate immune function of complement cascade in HFF.
      Complement inhibition and the presence of C-terminal fragment of perlecan
      suggested possible links to angiogenesis which is a vital process in
      folliculogenesis and placental development. Differences in proteins associated
      with blood coagulation were also found in the follicular milieu. Several specific
      proteins were observed, many of which have not yet been associated with
      follicle/oocyte maturation. These proteins together with their regulatory
      pathways may play a vital role in the reproductive process.

PMID- 20058867
TI  - Identification of bisprenylated benzoic acid derivatives from yerba santa
      (Eriodictyon ssp.) using sensory-guided fractionation.
AB  - Due to certain off-flavor problems and lacking bitter masking effects with Yerba
      Santa (Eriodictyon angustifolium and E. californicum) extracts, which are also
      described as bitter, herbal, medicinal, phenolic, or astringent, methanolic
      extracts were fractionated and evaluated for their taste properties using a high
      temperature liquid chromatography (HTLC)-based approach. The taste-guided
      fractionation led to the identification of a series of novel bisprenylated
      benzoic acids (erionic acids A (1), B (2), C (3), D (4), E (5), and F (6) and
      eriolic acids A (7), B (8), C (9), and D (10), respectively), along with the
      known flavonoids eriodictyol, homoeriodictyol, hesperetin, and chrysoeriol. The
      new compounds were isolated in larger amounts for characterization from Narrow
      Leaf Yerba Santa (E. angustifolium) and California Yerba Santa (E. californicum),
      respectively, using fast centrifugal partition chromatography (FCPC) and HTLC.
      The structures were elucidated using one and two-dimensional NMR spectroscopy and
      high resolution mass spectrometry (HR-MS). For E. californicum, data regarding
      seasonal and climatic variation of the eriolic acid contents and of the
      flavonoids were collected. The flavor properties of some of the isolated new
      compounds were evaluated; they showed strong off-flavor characteristics, such as
      bitter, astringent, phenolic, or woody, and may contribute to the sensory effects
      observed for crude Yerba Santa extracts. Erionic acid C (3) was not only able to
      increase the absolute bitterness but also to extinguish the bitter masking effect
      of homoeriodictyol in a caffeine solution.

PMID- 20058868
TI  - Mathematical model for the characterization and objective comparison of
      antioxidant activities.
AB  - The available data about the interference of antioxidants in the kinetics of
      lipid oxidation are abundant, but often they allow only semiquantitative
      conclusions, not always with sufficient basis. One of the causes of this problem
      is the absence of formal models able to guide the experimental design and to
      calculate characterizing parameters. In this regard, the model which we propose
      allows us to obtain the simultaneous solution of a series of oxidation kinetics
      in the presence of any number of antioxidant concentrations. It describes
      satisfactorily simulations in which substrate and antioxidant compete for oxygen
      in a second order kinetic scheme, as well as experimental results from other
      authors, in different systems and under different conditions. Its application is
      simple, it provides parametric estimates which characterize both the oxidative
      process and the antioxidant activity, and it facilitates rigorous comparisons
      among the effects of different compounds and experimental approaches. In all
      experimental data tested, the calculated parameters were always statistically
      significant (Student's t test, alpha = 0.05), the equations were consistent
      (Fisher's F-test), and the goodness of fit parameters (adj r(2), adjusted
      coefficients of multiple determination) were up to 0.97.

PMID- 20058869
TI  - Fluctuations of water near extended hydrophobic and hydrophilic surfaces.
AB  - We use molecular dynamics simulations of the SPC-E model of liquid water to
      derive probability distributions for water density fluctuations in probe volumes
      of different shapes and sizes, both in the bulk as well as near hydrophobic and
      hydrophilic surfaces. Our results are obtained with a biased sampling of coarse
      grained densities that is easily combined with molecular dynamics integration
      algorithms. Our principal result is that the probability for density fluctuations
      of water near a hydrophobic surface, with or without surface water attractions,
      is akin to density fluctuations at the water-vapor interface. Specifically, the
      probability of density depletion near the surface is significantly larger than
      that in the bulk, and this enhanced probability is responsible for hydrophobic
      forces of assembly. In contrast, we find that the statistics of water density
      fluctuations near a model hydrophilic surface are similar to that in the bulk.

PMID- 20058870
TI  - STM study on nonionic fluorosurfactant zonyl FSN Self-Assembly on Au(100):
      [array: see text] molecular lattice, corrugations, and adsorbate-enhanced
      mobility.
AB  - Nonionic fluorosurfactant zonyl FSN self-assembly on Au(100) is investigated by
      using scanning tunneling microscopy under ambient conditions. High-resolution STM
      images reveal that a [array: see text] arrangement of the FSN SAMs is formed on
      Au(100). Different from the uniform structure of FSN SAMs on Au(111), the
      adsorption sites of FSN molecules on Au(100) change gradually and form a kind of
      corrugated structure. The change in the adsorption sites probably originates from
      the repulsive force among FSN molecules because the nearest-neighbor distance of
      FSN molecules is 0.41 nm, which is smaller than 0.50 nm on Au(111). The mobility
      of surface atoms on the Au substrate is enhanced by the interaction between FSN
      molecules and the Au substrate; therefore, no Au island is observed on the FSN
      SAM-covered Au(100).

PMID- 20058871
TI  - Internal dynamics and energy transfer in dansylated POPAM dendrimers and their
      eosin complexes.
AB  - Internal dynamics of dansylated poly(propyleneamine) dendrimers (POPAM, G1-G4) in
      solution and excitation energy transfer from dansyls to eosin in POPAM-eosin
      complexes have been studied by time-resolved fluorescence spectroscopy and
      molecular dynamics (MD) simulations. Combining the results from fluorescence
      anisotropy and the MD simulation studies suggests three time domains for the
      internal dynamics of the G3 and G4 generations, about 60 ps for motions of the
      outer-sphere dansyls, 500-1000 ps for restricted motions of back-folded dansyls,
      and 1500-2600 ps for the overall rotation. For the smaller generations, the
      contribution from the restricted motions was not entirely evident. Eosin binding
      hinders fast rotation of the dansyl fragments in the largest G4 dendrimer, but
      the motion of back-folded dansyls is more hindered in the pure dendrimer. Both
      fluorescence anisotropy and MD results for the G4 dendrimer support the "soft"
      dendrimer picture with almost free mobility and substantial back-folding of the
      dansyls of the dendrimers in solution. Analysis of time-dependent spectral shifts
      of fluorescence reveals 20-30 ps excited-state solvation relaxation around a
      single dansyl of a dendrimer. Dendrimer-independent excitation energy transfer
      from 4 to 8 ps from dansyls to eosins in POPAM-eosin complexes G2-G4 was
      observed.

PMID- 20058872
TI  - Mechanically robust tri-wing graphene nanoribbons with tunable electronic and
      magnetic properties.
AB  - Inspired by strong mechanical stability of "Y"-shaped beams for building
      construction, we design a new class of quasi-one-dimensional graphene
      nanostructures, namely, tri-wing graphene (TWG) nanoribbons. TWG possesses
      significantly augmented mechanical stability against torsional and compression
      forces, and also each wing of the TWG can retain independent electronic
      properties of the constituent graphene nanoribbons. As such, by tailoring the
      wing structures, the TWGs can provide broader property tunability for
      nanoelectronic application. In addition, zigzag-edged TWG is a metallic
      ferromagnet with a large magnetic moment. When its edges are decorated with
      suitable chemical functional groups, a TWG can be converted to a half metal for
      potential spintronic applications.

PMID- 20058873
TI  - Bistability and oscillatory motion of natural nanomembranes appearing within
      monolayer graphene on silicon dioxide.
AB  - The truly two-dimensional material graphene is an ideal candidate for
      nanoelectromechanics due to its large strength and mobility. Here we show that
      graphene flakes provide natural nanomembranes of diameter down to 3 nm within its
      intrinsic rippling. The membranes can be lifted either reversibly or
      hysteretically by the tip of a scanning tunneling microscope. The clamped
      membrane model including van-der-Waals and dielectric forces explains the results
      quantitatively. AC-fields oscillate the membranes, which might lead to a
      completely novel approach to controlled quantized oscillations or single atom
      mass detection.

PMID- 20058874
TI  - Coulomb-controlled single electron field emission via a freely suspended metallic
      island.
AB  - We observe Coulomb blockade in the field-emission current of a metallic island
      between two electrodes freely suspended by thin tunneling barriers. A third
      electrode serves as a gating contact to trace the Coulomb staircase of the
      device. Coulomb blockade is revealed at 77 K in conjunction with field emission.
      The measurements are in very good agreement with a theoretical model, taking into
      account orthodox Coulomb blockade and field emission.

PMID- 20058875
TI  - Isobaric tagging-based selection and quantitation of cerebrospinal fluid tryptic
      peptides with reporter calibration curves.
AB  - In the past few years, mass spectrometry (MS) has emerged as an efficient tool
      for the multiplexed peptide and protein concentration determination by isotope
      dilution. Despite the growing use of isobaric tagging to perform relative
      quantitation for the discovery of potential biomarkers in biological fluids, no
      real application has so far been presented for their absolute quantitation.
      Isobaric tandem mass tags (TMTs) were used herein for the selection and
      quantitation of tryptic peptides derived from brain damage related proteins in
      cerebrospinal fluid (CSF). Proteotypic tryptic peptide analogues were
      synthesized, prepared in four reference amounts, differentially labeled with four
      isobaric TMTs with reporter-ions at m/z = 128.1, 129.1, 130.1, and 131.1, and
      mixed with CSF sample previously labeled with TMT 126.1. Off-gel electrophoresis
      (OGE) was used as first-dimension separation of the pooled sample. The resulting
      fractions were analyzed with reversed-phase liquid chromatography (RP-LC) tandem
      mass spectrometry (MS/MS), using tandem time-of-flight (TOF/TOF) and hybrid
      linear ion trap-orbitrap (LTQ-OT) instruments. Under collision-induced
      dissociation (CID) or higher-energy C-trap dissociation (HCD), the release of the
      reporter fragments from the TMT-labeled peptide standards provided an internal
      calibration curve to assess the concentration of these peptides in the CSF. This
      tool also allowed identifying selectively these peptides in CSF as only the
      targeted peptides showed specific fragmentation pattern in the TMT reporter-ion
      zone of the tandem mass spectra. Assays for the concentration measurements of
      peptides from PARK7, GSTP1, NDKA, and S100B proteins in CSF were further
      characterized using this novel, efficient, and straightforward approach.

PMID- 20058876
TI  - Exploring the human leukocyte phosphoproteome using a microfluidic reversed-phase
      TiO2-reversed-phase high-performance liquid chromatography phosphochip coupled to
      a quadrupole time-of-flight mass spectrometer.
AB  - The study of protein phosphorylation events is one of the most important
      challenges in proteome analysis. Despite the importance of phosphorylation for
      many regulatory processes in cells and many years of phosphoprotein and
      phosphopeptide research, the identification and characterization of
      phosphorylation by mass spectrometry is still a challenging task. Recently, we
      introduced an approach that facilitates the analysis of phosphopeptides by
      performing automated, online, TiO(2) enrichment of phosphopeptides prior to mass
      spectrometry (MS) analysis. The implementation of that method on a "plug-and
      play" microfluidic high-performance liquid chromatography (HPLC) chip design will
      potentially open up efficient phosphopeptide enrichment methods enabling
      phosphoproteomics analyses by a broader research community. Following our initial
      proof of principle, whereby the device was coupled to an ion trap, we now show
      that this so-called phosphochip is capable of the enrichment of large numbers of
      phosphopeptides from complex cellular lysates, which can be more readily
      identified when coupled to a higher resolution quadrupole time-of-flight (Q-TOF)
      mass spectrometer. We use the phosphochip-Q-TOF setup to explore the
      phosphoproteome of nonstimulated primary human leukocytes where we identify 1012
      unique phosphopeptides corresponding to 960 different phosphorylation sites
      providing for the first time an overview of the phosphoproteome of these
      important circulating white blood cells.

PMID- 20058877
TI  - Quantitative determination of acetylcholine and choline in microdialysis samples
      by MALDI-TOF MS.
AB  - A simple, sensitive, and fast matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF MS) method was developed for the
      determination of acetylcholine (ACh) and choline (Ch) in microdialysis samples.
      An optimized dried droplet preparation with the common matrix alpha-cyano-4
      hydroxycinnamic acid (CHCA) was used. Limits of detection [signal-to-noise ratio
      (S/N) = 3] of 0.3 fmol/microL for ACh and 20 fmol/microL for Ch were found using
      standards diluted in artificial cerebrospinal fluid (aCSF). The limit of
      quantification (LOQ) for ACh was 1 fmol/microL, and excellent linearity (R(2) =
      0.9996) was maintained over the range of 1-1000 fmol/microL. Choline was
      quantified over the range of 0.1-50 pmol/microL, also with excellent linearity
      (R(2) = 0.9995). Good accuracy and precision were obtained for all concentrations
      within the range of the standard curve. The developed method was successfully
      used for the determination of ACh and Ch in mouse brain microdialysis samples.
      The samples were quantified by a calibration curve and also by the method of
      standard addition. Despite the high salt content of the perfusion fluid (>150
      mM), a direct measurement was possible. To the authors' knowledge, this is the
      first published method to determine acetylcholine and choline in microdialysis
      samples by MALDI-TOF MS. The method presented significantly reduces the needed
      analysis time, as only approximately 10 s/sample is required, and it is also
      possible to improve the temporal resolution, because only approximately 1 microL
      of sample is needed.

PMID- 20058878
TI  - Immunoglobulin G glycopeptide profiling by matrix-assisted laser desorption
      ionization Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Immunoglobulin G (IgG) fragment crystallizable (Fc) glycosylation is essential
      for Fc-receptor-mediated activities. Changes in IgG Fc glycosylation have been
      found to be associated with various diseases. Here we describe a high-throughput
      IgG glycosylation profiling method. Sample preparation is performed in 96-well
      plate format: IgGs are purified from 2 microL of human plasma using immobilized
      protein A. IgGs are cleaved with trypsin, and the resulting glycopeptides are
      purified by reversed-phase or hydrophilic interaction solid-phase extraction.
      Glycopeptides are analyzed by intermediate pressure matrix-assisted laser
      desorption ionization Fourier transform ion cyclotron resonance mass spectrometry
      (MALDI-FTICR-MS). Notably, both dihydroxybenzoic acid (DHB) and alpha-cyano-4
      hydroxycinnamic acid (CHCA) matrixes allowed the registration of sialylated as
      well as nonsialylated glycopeptides. Data were automatically processed, and IgG
      isotype-specific Fc glycosylation profiles were obtained. The entire method
      showed an interday variation below 10% for the six major glycoforms of both IgG1
      and IgG2. The method was found suitable for isotype-specific high-throughput IgG
      glycosylation profiling from human plasma. As an example we successfully applied
      the method to profile the IgG glycosylation of 62 human samples.

PMID- 20058879
TI  - Integrated microfluidic device for automated single cell analysis using
      electrophoretic separation and electrospray ionization mass spectrometry.
AB  - A microfabricated fluidic device was developed for the automated real-time
      analysis of individual cells using capillary electrophoresis (CE) and
      electrospray ionization-mass spectrometry (ESI-MS). The microfluidic structure
      incorporates a means for rapid lysis of single cells within a free solution
      electrophoresis channel, where cellular constituents were separated, and an
      integrated electrospray emitter for ionization of separated components. The
      eluent was characterized using mass spectrometry. Human erythrocytes were used as
      a model system for this study. In this monolithically integrated device, cell
      lysis occurs at a channel intersection using a combination of rapid buffer
      exchange and an increase in electric field strength. An electroosmotic pump is
      incorporated at the end of the electrophoretic separation channel to direct
      eluent to the integrated electrospray emitter. The dissociated heme group and the
      alpha and beta subunits of hemoglobin from individual erythrocytes were detected
      as cells continuously flowed through the device. The average analysis throughput
      was approximately 12 cells per minute, demonstrating the potential of this method
      for high-throughput single cell analysis.

PMID- 20058880
TI  - Dynamics of the beta2-adrenergic G-protein coupled receptor revealed by hydrogen
      deuterium exchange.
AB  - To examine the molecular details of ligand activation of G-protein coupled
      receptors (GPCRs), emphasis has been placed on structure determination of these
      receptors with stabilizing ligands. Here we present the methodology for receptor
      dynamics characterization of the GPCR human beta(2) adrenergic receptor bound to
      the inverse agonist carazolol using the technique of amide hydrogen/deuterium
      exchange coupled with mass spectrometry (HDX MS). The HDX MS profile of receptor
      bound to carazolol is consistent with thermal parameter observations in the
      crystal structure and provides additional information in highly dynamic regions
      of the receptor and chemical modifications demonstrating the highly complementary
      nature of the techniques. After optimization of HDX experimental conditions for
      this membrane protein, better than 89% sequence coverage was obtained for the
      receptor. The methodology presented paves the way for future analysis of
      beta(2)AR bound to pharmacologically distinct ligands as well as analysis of
      other GPCR family members.

PMID- 20058881
TI  - Peptide de novo sequencing using 157 nm photodissociation in a tandem time-of
      flight mass spectrometer.
AB  - It has previously been shown that photodissociation of tryptic peptide ions with
      157 nm light in a matrix-assisted laser desorption/ionization (MALDI) tandem time
      of-flight (TOF) mass spectrometer generates an abundance of x-type ions. A
      peptide de novo sequencing algorithm has now been developed to interpret these
      data. By combination of photodissociation and postsource decay (PSD) spectra, the
      algorithm identifies x-type ions and derives peptide sequences. The confidence of
      amino acid assignments is evaluated by observing complementary y-, v-, and w-type
      ions that provide additional constraints to sequence identification. In the
      analysis of 31 tryptic peptides from 4 model proteins, the algorithm identified
      322 (or 90.7%) of the 355 amino acids and made only 3 incorrect assignments. The
      other 30 amino acids were not identified because specific needed x-type ions were
      not detected. Based on the observation of v- and w-type ions, 45 of 50 detected
      leucine and isoleucine residues were successfully distinguished and there was
      only one mistake. The remaining four residues were not distinguished because the
      corresponding v- and w-type ions were not detected. These de novo sequencing
      results translated into successful identification of proteins through homology
      searches. To evaluate the robustness of the present sequencing approach, a
      collection of 266 tryptic peptides from 23 model proteins were analyzed and then
      sequenced. A total of 167 peptides yielded sequence tags of 5 or more residues.
      In 5 peptides, 1 or 2 residues were incorrectly assigned.

PMID- 20058882
TI  - Combined experimental and theoretical study of the vibronic spectra of
      perylenecarboximides.
AB  - Absorption and emission spectra of perylene-3,4-dicarboximide (PMI) and perylene
      3,4,9,10-tetracarboxdiimide (PDI) derivatives embedded in a thin polymer film
      were measured by room-temperature bulk and low-temperature single-molecule
      spectroscopy. In contrast to bulk line narrowing spectra, the low-temperature
      single-molecule data allowed to unambiguously resolve the vibrational fine
      structure of the emission spectra. Additionally, the emission spectra were
      calculated by quantum chemical methods within the Franck-Condon approximation for
      various N-substituted derivatives of PMI and PDI. The experimental as well as
      calculated emission spectra are dominated by two spectral regions of high
      vibronic activity, a band system ranging from the 0-0 transition (at DeltaE(0-0))
      down to 600 cm(-1) below DeltaE(0-0) and a band system between approximately 1250
      and 1700 cm(-1) below DeltaE(0-0). Apart from the wavenumber region close to
      DeltaE(0-0) (down to 100 cm(-1) below DeltaE(0-0)), good agreement is found
      between the calculated and experimental spectra, allowing a clear-cut assignment
      of the dominant vibrational modes. There are, however, discrepancies in the
      intensities in particular for low-frequency vibrational modes. These differences
      between theory and experiment are tentatively attributed to linear electron
      phonon coupling which is completely neglected in the calculations and hindered
      internal rotation that is not properly accounted for in the harmonic
      approximation. Furthermore, in the experimental spectra, at the bulk as well as
      the single-molecule level, significant differences between PMI and PDI are
      observed which are attributed to stronger interactions with the matrix
      environment in the case of PMI due to the permanent electric dipole moment of
      that molecule.

PMID- 20058883
TI  - Interaction of water with three granular biopesticide formulations.
AB  - Two obstacles for biopesticide commercialization, long shelf life and reliable
      efficacy, are both affected by moisture availability. Three biopesticide delivery
      systems, TRE-G, PEC-G, and PESTA, were analyzed by dynamic vapor sorption
      analysis. The objective was to investigate the moisture sorption profile of each
      system in air at 25 degrees C and a relative humidity (RH) ranging from 0 to 90%.
      The formulations sorbed up to 12.7% moisture. In rehydrating from 0.00 to 90% RH,
      TRE-G and PEC-G were >or=63% and >or=58% faster than Pesta, respectively. In
      losing moisture from 90 to 0.00% RH, Pesta was 3.4 and 2.3 times slower than TRE
      G and PEC-G, respectively. The GAB model was inadequate for describing moisture
      sorption, but the Young and Nelson model showed good correlation (r > 0.990) for
      all three formulations. Moisture distribution for all formulations was obtained.
      The implications of the findings as they relate to shelf life and dew period
      requirements of biopesticides are discussed.

PMID- 20058884
TI  - Prediction of partial molar volumes of amino acids and small peptides: counting
      atoms versus topological indices.
AB  - Experimental data of partial molar volumes of amino acids and small peptides were
      compiled from several publications and enabled us to perform a predicative
      analysis based on quantitative structure-property relationships (QSPR). Based on
      the simplest level of the descriptors, the new method has high accuracy and was
      found to be more reliable when compared to the latter QSPR method based on
      topological indexes. Incorporation of isoelectric pH and 3-D solvent-accessible
      surface area parameters increased the predictability of the equation to a small
      extent. Cross-validation studies show that this method is successful in
      predicting the partial molar volumes of other noncoded amino acids, dipeptides,
      and diketopiperazine derivatives. This method is the beginning of new studies for
      larger peptides and proteins. It also can be suggested to be used for molecules
      that contain the same type of atoms as an amino acid.

PMID- 20058885
TI  - Nitric oxide beam intensity oscillations induced by the combined action of a
      static and a radio frequency electric field.
AB  - This paper details an experimental and theoretical investigation in which a
      simplified version of the molecular beam electric resonance technique is employed
      that requires the use of a C-field only. In the experiment the forward intensity
      of a NO beam is measured as a function of the frequency of the oscillating
      electric field over the 900-1460 kHz range. Specifically, the interaction of the
      NO beam with a radio frequency (rf) field of 1.12 kV/m amplitude and -610 kV/m
      (2) of gradient at the horizontal plane during 72 micros produces a series of
      oscillations in the transmitted beam intensity. The theoretical analysis shows
      how the interaction between a beam of NO molecules and both a static and
      oscillating rf field produces interferences in the forward beam intensity and how
      the observed interferences are due to superposition of molecular internal states.
      Furthermore, the interference model reproduces satisfactorily the observed beam
      intensity oscillations. The present technique could be useful for the development
      of new schemes to achieve coherent control of molecular processes using
      radiowaves.

PMID- 20058886
TI  - Excited-state energies and electronic couplings of DNA base dimers.
AB  - The singlet excited electronic states of two pi-stacked thymine molecules and
      their splittings due to electronic coupling have been investigated with a variety
      of computational methods. Focus has been given on the effect of intermolecular
      distance on these energies and couplings. Single-reference methods, CIS, CIS(2),
      EOM-CCSD, TDDFT, and the multireference method CASSCF, have been used, and their
      performance has been compared. It is found that the excited-state energies are
      very sensitive to the applied method but the couplings are not as sensitive.
      Inclusion of diffuse functions in the basis set also affects the excitation
      energies significantly but not the couplings. TDDFT is inadequate in describing
      the states and their coupling, while CIS(2) gives results very similar to EOM
      CCSD. Excited states of cytosine and adenine pi-stacked dimers were also obtained
      and compared with those of thymine dimers to gain a more general picture of
      excited states in pi-stacked DNA base dimers. The coupling is very sensitive to
      the relative position and orientation of the bases, indicating great variation in
      the degree of delocalization of the excited states between stacked bases in
      natural DNA as it fluctuates.

PMID- 20058887
TI  - Photoelectron spectroscopy of C60Fn- and C60Fm2- (n = 17, 33, 35, 43, 45, 47; m =
      34, 46) in the gas phase and the generation and characterization of C1-C60F47-
      and D2-C60F44 in solution.
AB  - A photoelectron spectroscopy investigation of the fluorofullerene anions
      C(60)F(n)(-) (n = 17, 33, 35, 43, 45, 47) and the doubly charged anions
      C(60)F(34)(2-) and C(60)F(46)(2-) is reported. The first electron affinities for
      the corresponding neutral molecules, C(60)F(n), were directly measured and were
      found to increase as n increased, reaching the extremely high value of 5.66 +/-
      0.10 eV for C(60)F(47). Density functional calculations suggest that the
      experimentally observed species C(60)F(17)(-), C(60)F(35)(-), and C(60)F(47)(-)
      were each formed by reductive defluorination of the parent fluorofullerene, C(3v)
      C(60)F(18), C(60)F(36) (a mixture of isomers), and D(3)-C(60)F(48), respectively,
      without rearrangement of the remaining fluorine atoms. The DFT-predicted
      stability of C(60)F(47)(-) was verified by its generation by chemical reduction
      from D(3)-C(60)F(48) in chloroform solution at 25 degrees C and its
      characterization by mass spectrometry and (19)F NMR spectroscopy. Further
      reductive defluorination of C(60)F(47)(-) in solution resulted in the selective
      generation of a new fluorofullerene, D(2)-C(60)F(44), which was also
      characterized by mass spectrometry and (19)F NMR spectroscopy.

PMID- 20058888
TI  - Specific volume-hole volume correlations in amorphous carbohydrates: effect of
      temperature, molecular weight, and water content.
AB  - The specific volume and the nanostructure of the free volume of amorphous blends
      of maltose with a narrow molecular weight distribution maltopolymer were
      systematically studied as a function of temperature, water content, pressure, and
      blend composition. Correlations between the hole free volume and the specific
      volume were investigated in the glassy and rubbery phases and in solution using
      positron annihilation lifetime spectroscopy (PALS) and pressure-volume
      temperature (PVT) measurements, with the aim to provide a consolidated
      mechanistic understanding of the relation between changes in molecular packing
      and at the molecular level and the behavior of the specific volume at the
      macrolevel. Both specific volume and hole volume show a linear dependence on the
      temperature, but with a slope which is higher in the rubbery state than in the
      glassy state. As a function of temperature, the hole volume and the specific
      volume are linearly related, with no discontinuity at the glass transition
      temperature (T(g)). In the glassy state, both the specific volume and the hole
      volume decrease nonlinearly with the addition of maltose to the maltopolymer
      matrix, due to a more efficient molecular packing. For variations in carbohydrate
      composition, a linear dependence between the hole volume and the specific volume
      was again observed. The role of water was found to be significantly more complex,
      with increasing water content causing an increase in density in both the glassy
      and rubbery phases indicating that water exists in a highly dispersed state with
      a significantly lower specific molar volume than in bulk water. At very low water
      contents, the hole volume and the specific volume both decrease with increasing
      water content, which suggests that water acts as both a hole filler and a
      plasticizer. In the glassy state at slightly higher water contents, the specific
      volume continues to slowly decrease, but the hole size passes through a minimum
      before it starts to increase. This gives rise to a negative correlation between
      the hole volume and the specific volume which has not previously been observed
      and which can be interpreted in terms of water molecules which are dispersed
      within the glassy carbohydrate matrix and which thereby influence the hydrogen
      bonding between the carbohydrate molecules.

PMID- 20058889
TI  - Electron transfer properties and hydrogen peroxide electrocatalysis of cytochrome
      c variants at positions 67 and 80.
AB  - Replacement of the axial Met80 heme ligand in electrode-immobilized cytochrome c
      with a noncoordinating Ala residue and alteration of the hydrogen bonding network
      in the region nearby following substitution of Tyr67 were investigated as
      effectors of the thermodynamics and kinetics of the protein-electrode electron
      transfer (ET) and the heme-mediated electrocatalytic reduction of H(2)O(2). To
      this end, the voltammetry of the Met80Ala, Met80Ala/Tyr67His, and
      Met80Ala/Tyr67Ala variants of yeast iso-1-cytochrome c chemisorbed on
      carboxyalkanethiol self-assembled monolayers was measured at varying temperature
      and hydrogen peroxide concentration. The thermodynamic study shows that insertion
      of His and Ala residues in place of Tyr67 results mainly in differences in
      protein-solvent interactions at the heme crevice with no relevant effects on the
      E degrees' values at pH 7, which for single and double variants range from
      approximately -0.200 to -0.220 V (vs SHE). On the contrary, both double variants
      show much lower ET rates compared to Met80Ala, most likely as a consequence of a
      change in the ET pathways. In the present nondenaturing immobilizing conditions,
      and with hydrogen peroxide concentrations in the micromolar range, the variants
      catalyze H(2)O(2) reduction at the electrode, whereas wild-type cytochrome c does
      not. H(2)O(2) electrocatalysis occurs with an efficient mechanism likely
      involving a fast catalase-like process followed by electrocatalytic reduction of
      the resulting dioxygen at the electrode. Comparison of Met80Ala/Tyr67His with
      Met80Ala/Tyr67Ala shows that the presence of a general acid-base residue for
      H(2)O(2) recognition and binding through H-bonding in the distal heme site is a
      key requisite for the reductive turnover of this substrate.

PMID- 20058890
TI  - Carbon nanotube effect on polyaniline morphology in water dispersible composites.
AB  - A straightforward, template-free chemical oxidative polymerization of aniline was
      used to prepare nanofibrillar polyaniline (nf-PANI) and a set of corresponding
      composites with multiwall carbon nanotubes (MWNTs). All the products showed
      remarkable water dispersibility since they are formed by hydrophilic particles of
      nanometric size. A comparative study performed on composites in a wide range of
      MWNT loadings has led to two main conclusions: on one hand, the presence of MWNTs
      affects neither the chemical structure nor the crystallinity of polyaniline. On
      the other hand, even small amounts of MWNTs have a significant effect on the
      morphology of polyaniline in composites. This effect is noticeable not only in
      electron microscopy images but also in the UV-vis absorbance of water dispersions
      and electrical conductivity behavior in the solid state. Competition between
      nucleation sites during polymerization is proposed as an explanation for these
      phenomena.

PMID- 20058891
TI  - Access to alpha-substituted amino acid derivatives via 1,3-dipolar cycloaddition
      of alpha-amino ester derived nitrones.
AB  - Amino acid derived nitrones were conveniently synthesized in good-to-excellent
      yields by condensation of alpha-ketoesters with N-benzylhydroxylamine. The
      cycloaddition reactions of these nitrones with different alkenes were
      investigated under thermal solvent-free conditions. Considering conversions,
      yields, and selectivities, alkyl vinyl ethers have proven to be valuable partners
      to achieve this transformation, which creates a tetrafunctionalized stereogenic
      quaternary center. From the adducts derived from vinyl ethers, a three-step
      access to highly functionalized alpha-substituted amino acid derivatives is
      described.

PMID- 20058892
TI  - Highly efficient and mild method for regioselective de-O-benzylation of
      saccharides by Co2(CO)8-Et3SiH-CO reagent system.
AB  - A highly efficient and mild method for the de-O-benzylation of protected
      saccharides was developed by transforming terminal benzyl ethers into silyl
      ethers using Co(2)(CO)(8)-Et(3)SiH under 1 atm of CO. The method was successfully
      used for the de-O-benzylation of perbenzylated monosaccharides with various
      anomeric protecting groups, as well as natural disaccharides and trisaccharides
      such as sucrose, raffinose, and melezitose in good yields (>80%).

PMID- 20058893
TI  - Tandem reactions with chiral enolates: preparation of allylic alcohols via
      trapping with vinyl oxiranes.
AB  - An opening of vinyl oxiranes has been accomplished with Zn and Al enolates
      resulting from asymmetric conjugate addition reactions on cyclic enones. This
      novel tandem procedure affords the adducts in moderate to good yields,
      enantioselectivities up to 98%, and moderate to good cis/trans selectivities.
      This provides potentially useful synthetic substrates to prepare complex bicyclic
      compounds.

PMID- 20058894
TI  - Dynamical crossover and breakdown of the Stokes-Einstein relation in confined
      water and in methanol-diluted bulk water.
AB  - Using nuclear magnetic resonance and quasi-elastic neutron scattering
      spectroscopic techniques, we obtain experimental evidence of a well-defined
      dynamic crossover temperature T(L) in supercooled water. We consider three
      different geometrical environments: (i) water confined in a nanotube (quasi-one
      dimensional water), (ii) water in the first hydration layer of the lysozyme
      protein (quasi-two-dimensional water), and (iii) water in a mixture with methanol
      at a methanol molar fraction of x = 0.22 (quasi-three-dimensional water). The
      temperature predicted using a power law approach to analyze the bulk water
      viscosity in the super-Arrhenius regime defines the fragile-to-strong transition
      and the Stokes-Einstein relation breakdown recently observed in confined water.
      Our experiments show that these observed processes are independent of the system
      dimension d and are instead caused by the onset of an extended hydrogen-bond
      network that governs the dynamical properties of water as it approaches dynamic
      arrest.

PMID- 20058895
TI  - Molecular modeling of crystalline alkylthiophene oligomers and polymers.
AB  - We present the results of a thorough molecular modeling study of several
      alkylthiophene-based oligomers and polymers. In particular, we consider two
      polymers whose limit-ordered crystal structures have been recently reported by
      our group, on the basis of powder X-ray data analysis: poly(3-(S)-2
      methylbutylthiophene) (P3MBT) and form I' of poly(3-butylthiophene) (P3BT). We
      first describe the development of a series general purpose force fields for the
      simulation of these and related systems. The force fields incorporate the results
      of ab initio calculations of the bond torsion energies of selected oligomers and
      differ in the set of atomic charges used to represent the electrostatic
      interactions. We then present the results of an extensive validation of these
      force fields, by means of molecular mechanics (MM) energy minimizations and
      molecular dynamics (MD) simulations of the crystal structures of these oligomers
      and polymers. While our "best" force field does not outperform the others on each
      of the investigated systems, it provides a balanced description of their overall
      structure and energetics. Finally, our MM minimizations and MD simulations
      confirm that the reported crystal structures of P3MBT and P3BT are stable and
      correspond to well-defined energetic minima. The room-temperature MD simulations
      reveal a certain degree of side-chain disorder, even in our virtually defect-free
      polymer crystal models.

PMID- 20058896
TI  - Supramolecular catalysis by cucurbit[7]uril and cyclodextrins: similarity and
      differences.
AB  - To understand the analogies and differences between the cucurbituril and
      cyclodextrin cavities different solvolytic reactions have been studied in the
      presence of cucurbit[7]uril, CB7, and beta-CD or its methylated derivative, DM
      beta-CD. Solvolysis of 1-bromoadamantane has been used as a test to evaluate the
      ability of the cavities to solvate the Br(-) leaving group. Obtained results show
      that in both cases the polarity inside the cavity is similar to that of a 70%
      ethanol:water mixture. Solvolysis of substituted benzoyl chlorides shows a great
      difference between the CB7 and DM-beta-CD cavity. Solvolysis of electron
      withdrawing substituted benzoyl chlorides (associative mechanism) is catalyzed by
      DM-beta-CD and inhibited by CB7. However, solvolysis of electron donating
      substituted benzoyl chlorides (dissociative mechanism) is catalyzed by CB7 and
      inhibited by DM-beta-CD. These experimental behaviors have been explained on the
      basis of different solvolytic mechanisms. Participation of the hydroxyl groups of
      the cyclodextrin as a nucleophile can explain the catalytic effect observed for
      solvolysis of benzoyl chlorides reacting by an associative mechanism. Solvolysis
      of benzoyl chlorides reacting by a dissociative mechanism is catalyzed by CB7 due
      to the ability of the CB7 cavity to stabilize the acylium ion developed in the
      transition state by electrostatic interactions.

PMID- 20058897
TI  - Commentary: Carbon nanotubes, CdSe nanocrystals, and electron-electron
      interaction.
AB  - To celebrate the tenth anniversary of Nano Letters, this short commentary
      discusses a scientific issue of current interest, increased electron-electron
      interactions in nanostructures. The two major factors of reduced dimensionality
      and low screening are analyzed. Carbon nanotubes and graphene are molecular in
      many of their properties and show strong electron-electron interactions. In
      specific circumstances, excited-state decay by exciton generation rather than
      phonon generation can be efficient in carbon nanotubes.

PMID- 20058898
TI  - Plasmon hybridization in individual gold nanocrystal dimers: direct observation
      of bright and dark modes.
AB  - We apply a nanomanipulation technique to assemble pairs of monodispersed
      octahedral gold nanocrystals (side length, 150 nm) along their major axes with a
      varying tip-to-tip separation (25-125 nm). These pairs are immobilized onto
      indium tin oxide coated silica substrates and studied as plasmonic dimers by
      polarization-selective total internal reflection (TIR) microscopy and
      spectroscopy. We confirm that the plasmon coupling modes with the scattering
      polarization along the incident light direction result from the transverse
      magnetic-polarized incident light, which induces two near-field-coupled dipole
      moments oriented normal to the air-substrate interface. In such cases, both in
      phase (antibonding) and antiphase (bonding) plasmon coupling modes can be
      directly observed with the incident light wave vector perpendicular and parallel
      to the dimer axis, respectively. The observation of antiphase plasmon coupling
      modes ("dark" plasmons) is made possible by the unique polarization nature of the
      TIR-generated evanescent field. Furthermore, with decreasing nanocrystal
      separation, the plasmon coupling modes shift to shorter wavelengths for the
      incident light perpendicular to the dimer axis, whereas relatively large red
      shifts of the plasmonic coupling modes are found for the parallel incident light.

PMID- 20058899
TI  - Confined growth of cyanide-based magnets in two dimensions.
AB  - Herein we report the first hybrid magnetic material resulting from the
      intercalation of a cyanide-based molecular magnet into a solid-state layered
      host. More specifically, the use of a diamagnetic cationic Zn(II)-Al(lII) layered
      double hydroxide host allows for the formation of an anionic two-dimensional
      ferromagnetic Ni(II)-Cr(III) Prussian Blue analogue, from the templated assembly
      of its ionic molecular components in the confined interlamellar space offered by
      the inorganic host.

PMID- 20058900
TI  - Density functional study of CO adsorbed on MnN (N = 2-8) clusters.
AB  - The geometry, electronic structure, magnetism, and adsorption properties of one
      CO molecule on the Mn(N) (N = 2-8) clusters have been investigated based on the
      density functional theory (DFT) with the spin polarized generalized gradient
      approximation. It is found that the CO molecule adsorbs on the atop site for N =
      2, 4, 7, 8 and on the bridge site for N = 3, 5, 6. The results of the calculated
      second-order energy differences of bare Mn(N) cluster indicate that the Mn(3),
      Mn(6), and Mn(8) clusters have relatively low stability. However, their
      corresponding CO complexes possess high adsorption ability implied by the C-O
      bond length, vibrational frequency, adsorption energy, and the charge transfer
      between the CO molecule and the clusters. Compared with bare Mn clusters, the
      adsorbing of a CO molecule enhances the magnetic moments of the Mn(N) clusters
      for N = 4, 6-8.

PMID- 20058901
TI  - Melting behavior and ionic conductivity in hydrophobic ionic liquids.
AB  - Four room-temperature ionic liquids (RTILs) based on the N-butyl-N-methyl
      pyrrolidinium (Pyr(14)(+)) and N-methyl-N-propyl pyrrolidinium cations
      (Pyr(13)(+)) and bis(trifluoromethanesulfonyl)imide (TFSI(-)) and
      bis(fluorosulfonyl)imide (FSI(-)) anions were intensively investigated during
      their melting. The diffusion coefficients of (1)H and (19)F were determined using
      pulsed field gradient (PFG) NMR to study the dynamics of the cations, anions, and
      ion pairs. The AC conductivities were measured to detect only the motion of the
      charged particles. The melting points of these ionic liquids were measured by DSC
      and verified by the temperature-dependent full width at half-maximum (FWHM) of
      the (1)H and (19)F NMR peaks. The diffusion and conductivity data at low
      temperatures gave information about the dynamics at the melting point and allowed
      specifying the way of melting. In addition, the diffusion coefficients of (1)H
      (D(H)) and (19)F (D(F)) and conductivity were correlated using the Nernst
      Einstein equation with respect to the existence of ion pairs. Our results show
      that in dependence on the cation different melting behaviors were identified. In
      the Pyr(14)-based ILs, ion pairs exist, which collapse above the melting point of
      the sample. This is in contrast to the Pyr(13)-based ILs where the present ion
      pairs in the crystal dissociate during the melting. Furthermore, the anions do
      not influence the melting behavior of the investigated Pyr(14) systems but affect
      the Pyr(13) ILs. This becomes apparent in species with a higher mobility during
      the breakup of the crystalline IL.

PMID- 20058902
TI  - Kinetics of glucose mutarotation assessed by an equal-amplitude paired polarized
      heterodyne polarimeter.
AB  - A dual-frequency equal-amplitude paired polarization heterodyne polarimeter
      (DEPHP) was set up in order to precisely measure the mutarotation rate constants
      of D-glucose in tridistilled water. The DEPHP is based on a balanced detector
      detection scheme for measurement of the optical rotation angle of D-glucose/water
      solution during the conversion process between alpha-D-glucose and beta-D-glucose
      while in a nonequilibrium state. The DEPHP can perform shot-noise-limited
      detection, so that the total optical rotation angle together with the
      mutarotation rate constants of alpha-D-glucose and beta-D-glucose conversion can
      be measured with high sensitivity. In this experiment, the sensitivity of the
      optical rotation angle measurement was 8.3 x 10(-5) deg/cm, while the total (k),
      forward (k(1)) and reverse (k(2)) mutarotation rate constants of D-glucose were
      found to be k = 7.67 x 10(-5) s(-1), k(1) = 2.76 x 10(-5) s(-1), and k(2) = 4.91
      x 10(-5) s(-1), respectively, in tridistilled water. Moreover, using the DEPHP,
      we can measure the specific rotation angles of alpha-D-glucose and beta-D-glucose
      in water at 632.8 nm. They were 105 degrees and 12 degrees, respectively.
      Finally, the detection sensitivity of the DEPHP system is also discussed.

PMID- 20058903
TI  - Solvated electron extinction coefficient and oscillator strength in high
      temperature water.
AB  - The decadic extinction coefficient of the hydrated electron is reported for the
      absorption maximum from room temperature to 380 degrees C. The extinction
      coefficient is established by relating the transient absorption of the hydrated
      electrons in the presence of a scavenger to the concentration of stable product
      produced in the same experiment. Scavengers used in this report are SF(6,) N(2)O,
      and methyl viologen. The room temperature value is established as 22,500 M(-1)
      cm(-1), higher by 10-20% than values used over the last several decades. We
      demonstrate how previous workers arrived at a low value by incorrect choice of a
      radiolysis yield value. With this revision, the integrated oscillator strength,
      corrected by refractive index, is definitely (ca. 10%) larger than unity. This
      result is fully consistent with EPR and resonance Raman results which indicate
      mixing of the hydrated electron wave function with solvent electronic orbitals.
      Oscillator strength appears to be conserved vs temperature.

PMID- 20058905
TI  - Synthesis of 1-(1H-indol-3-yl)-1,2-dihydroisoquinolines via AgOTf-catalyzed three
      component reactions of 2-alkynylbenzaldehydes, amines, and indoles.
AB  - Three-component reactions of 2-alkynylbenzaldehydes, amines, and indoles
      catalyzed by AgOTf under mild conditions afford the 1-(1H-indol-3-yl)-1,2
      dihydroisoquinolines in good yields. This silver-catalyzed tandem reaction is
      found to be workable with various indoles, anilines or alkyl amines, and 2
      alkynylbenzaldehydes with electron-withdrawing groups attached on the aromatic
      backbone.

PMID- 20058904
TI  - Biophysical properties of the eukaryotic ribosomal stalk.
AB  - The landing platform for the translational GTPases is located on the 60S
      ribosomal subunit and is referred to as a GTPase-associated center. The most
      distinctive feature of this center is an oligomeric complex, the stalk,
      responsible for the recruitment of translation factors and stimulation of
      translation factor-dependent GTP hydrolysis. In eukaryotes, the stalk has been
      investigated in vitro and in vivo, but most information available concerns its
      individual components only. In the present study, we provide an insight into the
      biophysical nature of the native stalk isolated from the yeast Saccharomyces
      cerevisiae. Using fluorescence, circular dichroism, and mass spectrometry
      analyses, we were able to characterize the natively formed yeast stalk, casting
      new light on the oligomeric properties of the complex and its quaternary
      topology, showing that folding and assembly are coupled processes. The pentameric
      stalk is an exceptionally stable structure with the protein core composed of P0,
      P1A, and P2B proteins and less tightly bound P1B and P2A capable of dissociating
      from the stalk core. We obtained also the whole picture of the posttranslational
      modifications at the logarithmic phase of yeast growth, using mass spectrometry
      approach, where P proteins are phosphorylated at a single serine residue, P0 may
      accept two phosphate groups, and P1A none. Additionally, only P1B undergoes N
      terminal acetylation after prior methionine removal.

PMID- 20058906
TI  - Synchrotron-based X-ray absorption spectroscopy for art conservation: looking
      back and looking forward.
AB  - A variety of analytical techniques augmented by the use of synchrotron radiation
      (SR), such as X-ray fluorescence (SR-XRF) and X-ray diffraction (SR-XRD), are now
      readily available, and they differ little, conceptually, from their common
      laboratory counterparts. Because of numerous advantages afforded by SR-based
      techniques over benchtop versions, however, SR methods have become popular with
      archaeologists, art historians, curators, and other researchers in the field of
      cultural heritage (CH). Although the CH community now commonly uses both SR-XRF
      and SR-XRD, the use of synchrotron-based X-ray absorption spectroscopy (SR-XAS)
      techniques remains marginal, mostly because CH specialists rarely interact with
      SR physicists. In this Account, we examine the basic principles and capabilities
      of XAS techniques in art preservation. XAS techniques offer a combination of
      features particularly well-suited for the chemical analysis of works of art. The
      methods are noninvasive, have low detection limits, afford high lateral
      resolution, and provide exceptional chemical sensitivity. These characteristics
      are highly desirable for the chemical characterization of precious,
      heterogeneous, and complex materials. In particular, the chemical mapping
      capability, with high spatial resolution that provides information about local
      composition and chemical states, even for trace elements, is a unique asset. The
      chemistry involved in both the object's history (that is, during fabrication) and
      future (that is, during preservation and restoration treatments) can be addressed
      by XAS. On the one hand, many studies seek to explain optical effects occurring
      in historical glasses or ceramics by probing the molecular environment of
      relevant chromophores. Hence, XAS can provide insight into craft skills that were
      mastered years, decades, or centuries ago but were lost over the course of time.
      On the other hand, XAS can also be used to characterize unwanted reactions, which
      are then considered alteration phenomena and can dramatically alter the object's
      original visual properties. In such cases, the bulk elemental composition is
      usually unchanged. Hence, monitoring oxidation state (or, more generally, other
      chemical modifications) can be of great importance. Recent applications of XAS in
      art conservation are reviewed and new trends are discussed, highlighting the
      value (and future possibilities) of XAS, which remains, given its potential,
      underutilized in the CH community.

PMID- 20058907
TI  - Nanoscale quantitative measurement of the potential of charged nanostructures by
      electrostatic and Kelvin probe force microscopy: unraveling electronic processes
      in complex materials.
AB  - In microelectronics and biology, many fundamental processes involve the exchange
      of charges between small objects, such as nanocrystals in photovoltaic blends or
      individual proteins in photosynthetic reactions. Because these nanoscale
      electronic processes strongly depend on the structure of the electroactive
      assemblies, a detailed understanding of these phenomena requires unraveling the
      relationship between the structure of the nano-object and its electronic
      function. Because of the fragility of the structures involved and the dynamic
      variance of the electric potential of each nanostructure during the charge
      generation and transport processes, understanding this structure-function
      relationship represents a great challenge. This Account discusses how our group
      and others have exploited scanning probe microscopy based approaches beyond
      imaging, particularly Kelvin probe force microscopy (KPFM), to map the potential
      of different nanostructures with a spatial and voltage resolution of a few
      nanometers and millivolts, respectively. We describe in detail how these
      techniques can provide researchers several types of chemical information. First,
      KPFM allows researchers to visualize the photogeneration and splitting of several
      unitary charges between well-defined nano-objects having complementary electron
      acceptor and -donor properties. In addition, this method maps charge injection
      and transport in thin layers of polycrystalline materials. Finally, KPFM can
      monitor the activity of immobilized chemical components of natural photosynthetic
      systems. In particular, researchers can use KPFM to measure the electric
      potential without physical contact between the tip and the nanostructure studied.
      These measurements exploit long-range electrostatic interactions between the
      scanning probe and the sample, which scale with the square of the probe-sample
      distance, d. While allowing minimal perturbation, these long-range interactions
      limit the resolution attainable in the measurement of potentials. Although the
      spatial resolution of KPFM is on the nanometer scale, it is inferior to that of
      other related techniques such as atomic force or scanning tunneling microscopy,
      which are based on short-range interactions scaling as d(-7) or e(-d),
      respectively. To overcome this problem, we have recently devised deconvolution
      procedures that allow us to quantify the electric potential of a nano-object
      removing the artifacts due to its nanometric size.

PMID- 20058908
TI  - Intrinsically resolution enhancing probes for confocal microscopy.
AB  - In recent years different implementations of superresolution microscopy based on
      targeted switching (STED, GSD, and SSIM) have been demonstrated. The key elements
      to break the diffraction barrier are two distinct molecular states that generate
      a saturable nonlinear fluorescence response with respect to the excitation
      intensity. In this paper, we demonstrate that a nonlinearity can even be encoded
      in fluorescent probes, which then increase the resolution of a standard confocal
      microscope. This nonlinearity is achieved by an intensity dependent blocking of
      the resonance energy transfer between a donor and one or more acceptor
      fluorophores, utilizing radical anion states of the acceptor. In proof-of
      principle experiments, we demonstrate a significant resolution increase using
      probes with different numbers of acceptor fluorophores. Quantitative description
      by a theoretical model paves the way for the development of fluorescent probes
      that can more than double the resolution of essentially any confocal microscope
      in all three dimensions.

PMID- 20058909
TI  - Bis-spirolabdane-type diterpenoids from Leonurus sibiricus.
AB  - Six new bis-spirolabdane-type diterpenoids, leosibirinone A (1), 3alpha
      acetoxyleoheteronone C (2), leosibirinone B (3), 3alpha-hydroxyleoheteronone A
      (4), 3alpha-acetoxyleoheteronone E (5), and 3alpha-acetoxy-15-epileoheteronone E
      (6), were isolated from the aerial parts of Leonurus sibiricus. Their structures
      were identified on the basis of 1D and 2D NMR, including (1)H-(1)H COSY, HSQC,
      HMBC, and NOESY spectroscopic analyses.

PMID- 20058910
TI  - Detection of HIV-1 specific monoclonal antibodies using enhancement of dye
      labeled antigenic peptides.
AB  - A simple bifunctional colorimetric/fluorescent sensing assay is demonstrated for
      the detection of HIV-1 specific antibodies. This assay makes use of a short
      peptide sequence coupled to an environmentally sensitive dye that absorbs and
      emits in the visible portion of the spectrum. The core peptide sequence is
      derived from the highly antigenic six-residue epitope of the HIV-1 p17 protein
      and is situated adjacent to a terminal cysteine residue which enables site
      specific fluorescent labeling with Cy3 cyanine dye. Interaction of the Cy3
      labeled p17 peptide with monoclonal anti-p17 antibody resulted in an up to 4-fold
      increase in dye absorption and greater than 5-fold increase in fluorescent
      emission, yielding a limit of detection as low as 73 pM for the target antibody.
      This initial study demonstrates both proof-of-concept for this approach and
      suggests that the resulting sensor could potentially be used as a rapid screening
      method for HIV-1 infection while requiring minimal equipment and reagents. The
      potential for utilizing this assay in simple field-portable point-of-care and
      diagnostic devices is discussed.

PMID- 20058911
TI  - Tuning of the surface biological behavior of poly(L-lactide)-based electrospun
      materials by polyelectrolyte complex formation.
AB  - Poly(L-lactide) (PLLA) and poly(L-lactide)/poly(ethylene glycol) (PLLA/PEG)
      electrospun fibrous materials coated with a polyelectrolyte complex (PEC) were
      prepared. This was achieved by consecutive deposition of a layer of N
      carboxyethylchitosan (CECh) and a layer of a double hydrophilic block copolymer,
      poly(ethylene oxide)-b-quaternized poly[2-(dimethylamino)ethyl methacrylate] (PEO
      b-PDMAEMAQ100), resulting in PEC formation between the two polyelectrolytes on
      the surface. Noteworthy, to improve the water wettability of the electrospun PLLA
      fibrous materials, that is, to enable more uniform deposition of the
      polyelectrolyte partners, water/ethanol mixed solvent was used for preparation of
      CECh and PEO-b-PDMAEMAQ100 solutions. The formation of PEC-based coating was
      demonstrated by means of scanning electron microscopy (SEM) and X-ray
      photoelectron spectroscopy (XPS). The PEC formation allows targeted modification
      of the biological behavior of the electrospun materials as evidenced by the
      performed tests in respect to blood cells and pathogenic microorganisms. In
      contrast to the pristine mats, the novel PEC-coated mats exhibit hemostatic
      properties and reduce the adhesion of pathogenic microorganisms.

PMID- 20058912
TI  - Amide spacing influences pDNA binding of poly(amidoamine)s.
AB  - Previously, a series of three poly(amidoamine)s was designed and synthesized by
      polymerizing oxylate, succinate, or adipate groups with pentaethylenehexamine.
      These resulting polymers (named O4, S4, and A4, respectively) were created as
      models to poly(glycoamidoamine) nucleic acid delivery agents to understand how
      the absence of hydroxyl groups and changes in the amide bond spacing affect
      polymer degradation, plasmid DNA (pDNA) encapsulation, toxicity, and transfection
      efficiency in vitro. To understand differences in the biological properties
      quantitatively, we investigated the mechanism of interaction between these
      macromolecules and pDNA to reveal differences in pDNA binding affinity and
      complexation as a function of structure. Herein, several analytical techniques
      such as dynamic light scattering, circular dichroism, thermal gravimetric
      analysis, isothermal titration calorimetry (ITC), and ethidium bromide exclusion
      assays were used to examine the pDNA binding strength of O4, S4, and A4, and the
      results are compared with the previous series of poly(glycoamidoamine)s. It was
      found that the length of the amide bond spacer in these nonhydroxylated analogs
      did affect the pDNA binding affinity to a small degree (binding affinity order A4
      > S4 > O4). The increase in binding affinity with longer methylene spacer was not
      due to hydrophobic interactions but likely from optimization in electrostatic
      interactions and hydrogen bond formation. Even though O4 was revealed to have the
      lowest pDNA binding affinity of the nonhydroxylated series, this polymer yields
      the highest cellular transfection efficiency, which is likely an effect of the
      faster hydrolysis rate.

PMID- 20058913
TI  - Degradation of poly(glycoamidoamine) DNA delivery vehicles: polyamide hydrolysis
      at physiological conditions promotes DNA release.
AB  - Poly(glycoamidoamine)s (PGAAs) are a group of efficient and degradable gene
      delivery vehicles that consist of three main functionalities: carbohydrate
      groups, secondary amines, and amide bonds. Herein, we have created
      nonhydroxylated models to these structures by polymerizing oxylate, succinate, or
      adipate groups with pentaethylenehexamine. The resulting polymers (named O4, S4,
      and A4, respectively) were created to understand how the absence of hydroxyl
      groups and changes in the amide bond spacing affect polymer degradation, plasmid
      DNA (pDNA) complexation, toxicity, and transfection efficiency in vitro. An
      additional model was also created that retains a galactaramide unit, but we have
      replaced the secondary amines with ethyleneoxide units (GO2) to understand the
      effects of the amine groups on polymer degradation. We have found that the
      secondary amines and hydroxyls are necessary to facilitate rapid degradation of
      these polymers, and analogues lacking hydroxyls or amines did not degrade over
      the time course of the study. Through electron-withdrawing and hydrogen bonding,
      the hydroxyls appear to activate the carbonyls of the amide bond to hydrolysis
      via an inductive electron withdrawing effect. Through titration experiments, PGAA
      degradation appears not to affect the polymer buffering capacity. Furthermore, we
      have found that PGAA degradation may enhance gene expression by releasing pDNA
      from polyplexes (polymer-pDNA complexes) and, thus, exposing it to undergo
      transcription and translation. The difference in the optimal pH that promotes
      degradation of the PGAAs and the hydroxyl-free analogues may prove to be a useful
      means to achieve pH-regulated DNA release from polyplexes by specifically
      modulating the chemical structures.

PMID- 20058914
TI  - Transformation of chiral polychlorinated biphenyls (PCBs) in a stream food web.
AB  - The enantiomeric composition of chiral PCB congeners was determined in Twelvemile
      Creek (Clemson, SC) to examine potential mechanisms of biotransformation in a
      stream food web. We measured enantiomeric fractions (EFs) of six PCB atropisomers
      (PCBs 84, 91, 95, 136, 149, and 174) in surface sediment, fine benthic organic
      matter (FBOM), coarse particulate organic matter (CPOM), periphyton, Asian clam,
      mayflies, yellowfin shiner, and semipermeable membrane devices (SPMDs) using gas
      chromatography (GC-ECD). Nonracemic EFs of PCBs 91, 95, 136, and 149 were
      measured in almost all samples. Enantiomeric compositions of PCBs 84 and 174 were
      infrequently detected with racemic EFs measured in samples except for a
      nonracemic EF of PCB 84 in clams. Nonracemic EFs of PCBs 91, 136, and 149 in
      SPMDs may be due to desorption of nonracemic residues from FBOM. EFs for some
      atropisomers were significantly different among FBOM, CPOM, and periphyton,
      suggesting that their microbial communities have different biotransformation
      processes. Nonracemic EFs in clams and fish suggest both in vivo
      biotransformation and uptake of nonracemic residues from their food sources.
      Longitudinal variability in EFs was generally low among congeners observed in
      matrices.

PMID- 20058915
TI  - Impact of uranyl-calcium-carbonato complexes on uranium(VI) adsorption to
      synthetic and natural sediments.
AB  - Adsorption on soil and sediment solids may decrease aqueous uranium
      concentrations and limit its propensity for migration in natural and contaminated
      settings. Uranium adsorption will be controlled in large part by its aqueous
      speciation, with a particular dependence on the presence of dissolved calcium and
      carbonate. Here we quantify the impact of uranyl speciation on adsorption to both
      goethite and sediments from the Hanford Clastic Dike and Oak Ridge Melton Branch
      Ridgetop formations. Hanford sediments were preconditioned with sodium acetate
      and acetic acid to remove carbonate grains, and Ca and carbonate were
      reintroduced at defined levels to provide a range of aqueous uranyl species.
      U(VI) adsorption is directly linked to UO(2)(2+) speciation, with the extent of
      retention decreasing with formation of ternary uranyl-calcium-carbonato species.
      Adsorption isotherms under the conditions studied are linear, and K(d) values
      decrease from 48 to 17 L kg(-1) for goethite, from 64 to 29 L kg (-1) for Hanford
      sediments, and from 95 to 51 L kg(-1) for Melton Branch sediments as the Ca
      concentration increases from 0 to 1 mM at pH 7. Our observations reveal that, in
      carbonate-bearing waters, neutral to slightly acidic pH values ( approximately 5)
      and limited dissolved calcium are optimal for uranium adsorption.

PMID- 20058916
TI  - Adsorption and reaction of trace gas-phase organic compounds on atmospheric water
      film surfaces: a critical review.
AB  - The air-water interface in atmospheric water films of aerosols and hydrometeors
      (fog, mist, ice, rain, and snow) presents an important surface for the adsorption
      and reaction of many organic trace gases and gaseous reactive oxidants (hydroxyl
      radical (OH(.)), ozone (O(3)), singlet oxygen (O(2)((1)Delta(g))), nitrate
      radicals (NO(3)(.)), and peroxy radicals (RO(2)(.)). Knowledge of the air-water
      interface partition constant of hydrophobic organic species is necessary for
      elucidating the significance of the interface in atmospheric fate and transport.
      Various methods of assessing both experimental and theoretical values of the
      thermodynamic partition constant and adsorption isotherm are described in this
      review. Further, the reactivity of trace gases with gas-phase oxidants (ozone and
      singlet oxygen) at the interface is summarized. Oxidation products are likely to
      be more water-soluble and precursors for secondary organic aerosols in
      hydrometeors. Estimation of characteristic times shows that heterogeneous
      photooxidation in water films can compete effectively with homogeneous gas-phase
      reactions for molecules in the atmosphere. This provides further support to the
      existing thesis that reactions of organic compounds at the air-water interface
      should be considered in gas-phase tropospheric chemistry.

PMID- 20058917
TI  - Comparison of FTIR and particle mass spectrometry for the measurement of
      particulate organic nitrates.
AB  - While multifunctional organic nitrates are formed during the atmospheric
      oxidation of volatile organic compounds, relatively little is known about their
      signatures in particle mass spectrometers. High resolution time-of-flight aerosol
      mass spectrometry (HR-ToF-AMS) and FTIR spectroscopy on particles impacted on
      ZnSe windows were applied to NH(4)NO(3), NaNO(3), and isosorbide 5-mononitrate
      (IMN) particles, and to secondary organic aerosol (SOA) from NO(3) radical
      reactions at 22 degrees C and 1 atm in air with alpha- and beta-pinene, 3-carene,
      limonene, and isoprene. For comparison, single particle laser ablation mass
      spectra (SPLAT II) were also obtained for IMN and SOA from the alpha-pinene
      reaction. The mass spectra of all particles exhibit significant intensity at m/z
      30, and for the SOA, weak peaks corresponding to various organic fragments
      containing nitrogen [C(x)H(y)N(z)O(a)](+) were identified using HR-ToF-AMS. The
      NO(+)/NO(2)(+) ratios from HR-ToF-AMS were 10-15 for IMN and the SOA from the
      alpha- and beta-pinene, 3-carene, and limonene reactions, approximately 5 for the
      isoprene reaction, 2.4 for NH(4)NO(3) and 80 for NaNO(3). The N/H ratios from HR
      ToF-AMS for the SOA were smaller by a factor of 2 to 4 than the -ONO(2)/C-H
      ratios measured using FTIR. FTIR has the advantage that it provides
      identification and quantification of functional groups. The NO(+)/NO(2)(+) ratio
      from HR-ToF-AMS can indicate organic nitrates if they are present at more than 15
      60% of the inorganic nitrate, depending on whether the latter is NH(4)NO(3) or
      NaNO(3). However, unique identification of specific organic nitrates is not
      possible with either method.

PMID- 20058918
TI  - Catalytic water oxidation by single-site ruthenium catalysts.
AB  - A series of monomeric ruthenium polypyridyl complexes have been synthesized and
      characterized, and their performance as water oxidation catalysts has been
      evaluated. The diversity of ligand environments and how they influence rates and
      reaction thermodynamics create a platform for catalyst design with controllable
      reactivity based on ligand variations.

PMID- 20058919
TI  - Photoisomerization of azobenzene units controls the reversible dispersion and
      reorganization of fibrous self-assembled systems.
AB  - N-(L-valyl-L-valyl-L-valyl)azobenzene-4-carboxamide [Azo(LVal)(3)] is a low
      molecular weight gelator that forms a photofunctional fibrous assembled system;
      this assembly undergoes dispersion/reorganization upon trans-to-cis
      photoisomerization, which, as a result of the breaking and reforming of hydrogen
      bonds, induces reversible sol-gel transitions. In this paper, we describe the
      mechanism by which azobenzene isomerization induces the breaking and
      reorganization of these assembled systems. We applied Fourier transform infrared
      spectroscopy to investigate the effect of the irradiation time on the change in
      absorption intensity in the amide I region. The lifetime of the cis isomer
      influences the photoinduced breaking and reforming of hydrogen bonds between
      trivalyl units. Because the cis isomer of Azo(LVal)(3) had a long lifetime, its
      assemblies underwent reversible phototriggered dispersion and organization. In
      contrast, the lifetime of the cis isomer of 4'-dimethylamino-N-(L-valyl-L-valyl-L
      valyl)azobenzene-4-carboxamide [pMR(LVal)(3)] was too short to disrupt the
      hydrogen bonds in its fibrous self-assembled system.

PMID- 20058920
TI  - Mechanistic duality in palladium-catalyzed cross-coupling reactions of
      aryldimethylsilanolates. intermediacy of an 8-Si-4 arylpalladium(II) silanolate.
AB  - The mechanism of palladium-catalyzed cross-coupling reactions of potassium (4
      methoxyphenyl)dimethyl silanolate has been investigated. Under catalysis by (t
      Bu(3)P)(2)Pd, the coupling with 1-bromo-4-fluorobenzene displays the following
      rate equation: rate = k(obs)[R(3)SiOK](0)[ArylBr](0), with k(obs) = k[(t
      Bu(3)P)(2)Pd](0.98). An independent study of the individual steps of the
      catalytic cycle has revealed a dual mechanistic pathway. The transmetalation can
      occur by a thermal process via an 8-Si-4 intermediate without the need for
      anionic activation. Additionally, arylsilanolates can serve as activators for
      transmetalation via a hypervalent 10-Si-5 siliconate intermediate.

PMID- 20058921
TI  - Metal-free highly regioselective aminotrifluoroacetoxylation of alkenes.
AB  - We report a highly regioselective metal-free oxidative cyclization of
      sulfonamides onto tethered, unactivated alkenes using hypervalent iodine and
      Bronsted acids. Under these conditions the acid counterion is incorporated into
      the cyclized products providing an overall aminotrifluoroacetoxylation of the
      alkene. An unusual preference for endo ring closure is exhibited in contrast to
      existing exo selective methods. Multiple ring sizes can be formed to access
      functionalized pyrrolidines, piperidines, and azepanes with a general preference
      for endo cyclization. A variety of substrate substitution patterns were tolerated
      to provide nitrogen-containing heterocycles with high regioselectivities and good
      to excellent diastereoselectivities.

PMID- 20058922
TI  - On the absolute configurational stability of bromonium and chloronium ions.
AB  - Halonium ions have long been established as the critical intermediates in
      halogenation and halofunctionalization of alkenes. Although these workhorse
      reactions have been extensively studied mechanistically and employed
      synthetically, the paucity of enantioselective variants is striking. A central
      problem in the development of catalytic enantioselective halofunctionalizations
      is the reversible formation of halonium ions and the facile olefin-to-olefin
      transfer. In this report, configurationally defined and enantiomerically enriched
      bromonium and chloronium ions are generated (by solvolysis of enantiomerically
      enriched precursors) and shown to be intercepted intermolecularly with high
      enantio- and diastereospecificity by various nucleophiles. Most importantly, the
      stereospecificity of capture is not significantly eroded in the presence of
      olefins.

PMID- 20058923
TI  - Chemoenzymatic conversion of linoleic acid into conjugated linoleic acid.
AB  - An efficient chemoenzymatic method for preparing conjugated linoleic acid (CLA)
      using free linoleic acid (LA) as a substrate is described. In the first step, LA
      was transformed into 10-hydroxy-cis-12-octadecenoic acid (HA) by the whole cells
      of Lactobacillus plantarum after 48 h of incubation. The preincubation of whole
      cells with 0.03% LA resulted in a better yield of HA (480 mg/g) compared to cells
      grown without LA. In a second fast microwave step, HA was converted to cis
      9,trans-11-octadecadienoic acid in the presence of iodine as a catalyst over a
      silica gel surface. The advantage of this method in preparing cis-9,trans-11 CLA
      is simple via the whole cell bioconversion of LA into HA via L. plantarum
      followed by the fast microwave-assisted synthesis of cis-9,trans-11 CLA in higher
      yields.

PMID- 20058924
TI  - Indolyne and aryne distortions and nucleophilic regioselectivites.
AB  - Density functional theory computations reproduce the surprisingly high
      regioselectivities in nucleophilic additions and cycloadditions to 4,5-indolynes
      and the low regioselectivities in the reactions of 5,6-indolynes. Transition
      state distortion energies control the regioselectivities, activating the 5 and 6
      positions over the 4 and 7 positions, leading to high preferences for 5- and 6
      substituted products from 4,5- and 6,7-indolynes, respectively. Orbital and
      electrostatic interactions have only minor effects, producing low
      regioselectivities in the reactions of 5,6-indolynes. The distortion model
      predicts high regioselectivities with 6,7-indolynes; these have been verified
      experimentally. The regioselectivities found with other arynes are explained on
      the basis of distortion energies that are reflected in reactant geometries.

PMID- 20058925
TI  - Effect of aqueous, acid, and alkaline thermal treatments on antinutritional
      factors content and protein quality in Lupinus campestris seed flour.
AB  - Lupinus campestris seeds grown in Mexico have a similar composition to soybean
      (44% protein, 13% lipids). Use of lupin seed in human and animal diets is limited
      by its quinolizidine alkaloids (QAs) and other antinutritional factor contents.
      The effect of aqueous, acid, and alkaline thermal debittering treatments with L.
      campestris seeds flour was evaluated on QAs, oligosaccharides (RFOs), and
      phenolic compounds (PCs) contents, as well as protein quality. The alkaline
      treatment most effectively eliminated QAs. Protein content increased from 430
      g/kg in untreated seeds to 543 in the aqueous treatment, 567 in the alkaline
      treatment, and 563 g/kg in the acid treatment. RFOs were eliminated in all
      treatments. The obtained sample with alkaline treatment had the best protein
      quality (2.04); this value was 17% lower than that of casein (2.45). The apparent
      digestibility was over 90% in all treatments, with the aqueous treatment
      exhibiting the best value (93%).

PMID- 20058926
TI  - Phenolic substance characterization and chemical and cell-based antioxidant
      activities of 11 lentils grown in the northern United States.
AB  - Chemical and cellular antioxidant activities and phenolic profiles of 11 lentil
      cultivars grown in the cool northern parts of the United States were
      investigated. Individual phenolic compounds, including phenolic acids, flavan-3
      ols, flavones, and anthocyanins, were further quantitatively investigated by
      HPLC. Cellular antioxidant activities (CAA) and peroxyl radical scavenging
      capacity (PRSC) were evaluated by fluorescence microplate reader. Cultivar Morton
      exhibited the highest individual flavan-3-ols (catechin and epicatechin) and
      total flavonoids, as well as the highest antioxidant properties (PRSC and CAA)
      among all lentils tested. Five phenolic acids of the benzoic types and their
      derivates (gallic, protocatechuic, 2,3,4-trihydroxybenzoic, p-hydroxybenzoic
      acid, and protocatechualdehyde) and four phenolic acids of the cinnamic type
      (chlorogenic, p-coumaric, m-coumaric, and sinapic acid) were detected in all
      lentil cultivars. Two flavan-3-ols [(+)-catechin and (-)-epicatechin] and one
      flavone (luteolin) were detected in all lentil cultivars. Among all phenolic
      compounds detected, sinapic acid was the predominant phenolic acid, and (+)
      catechin and (-)-epicatechin were the predominant flavonoids. These results
      showed that different phenotype lentils possessed considerable variations in
      their individual phenolic compounds, as well as chemical and cellular antioxidant
      activities. Caffeic acid, catechin, epicatechin, and total flavonoids
      significantly (p < 0.05) correlated with peroxyl radical scavenging assay.
      Cellular antioxidant assay significantly correlated with chemical antioxidant
      assay ORAC. The results from this study could be very interesting for breeding
      programs to improve lentils for use as functional foods.

PMID- 20058927
TI  - Effect of phytic acid on suicidal erythrocyte death.
AB  - Phytic acid, an anticarcinogenic food component, stimulates apoptosis of tumor
      cells. Similar to apoptosis, human erythrocytes may undergo suicidal death or
      eryptosis, characterized by cell membrane scrambling and cell shrinkage. Triggers
      of eryptosis include energy depletion. Phytate intake could cause anemia, an
      effect attributed to iron complexation. The present experiments explored whether
      phytic acid influences eryptosis. Supernatant hemoglobin concentration was
      determined to reveal hemolysis, annexin V-binding in FACS analysis was utilized
      to identify erythrocytes with scrambled cell membrane, forward scatter in FACS
      analysis was taken as a measure of cell volume, and a luciferin-luciferase assay
      was employed to determine erythrocyte ATP content. As a result, phytic acid
      (>or=1 mM) did not lead to significant hemolysis, but significantly increased the
      percentage of annexin V-binding erythrocytes, significantly decreased forward
      scatter, and significantly decreased cellular ATP content. In conclusion, phytic
      acid stimulates suicidal human erythrocyte death, an effect paralleling its
      proapoptotic effect on nucleated cells.

PMID- 20058928
TI  - Methylxanthines and phenolics content extracted during the consumption of mate
      (Ilex paraguariensis St. Hil) beverages.
AB  - "Chimarrao" and "terere" are popular beverages consumed in South America prepared
      using mate (Ilex paraguariensis St. Hil.). "Chimarrao" consists of a partial
      infusion where hot water is added, while "terere" is a total infusion, with
      addition of cold water. This study was designed to simulate preparation of these
      beverages for consumption, in order to estimate the total amount of xanthines and
      phenolic compounds in aqueous extracts that would be ingested by the consumer.
      Different commercial types of mate were employed for "chimarrao" preparation
      (native, smooth, traditional, and course-ground), and these were compared to
      "terere". In "chimarrao", beverages from coarse-ground mate showed the highest
      levels of xanthines. However, "terere" presented quantities 2.5 times higher than
      the beverage of the coarse-ground mate. Considering the total phenolics in
      "chimarrao", there was no difference between the types of herbs, but in "terere",
      the extraction of almost all of the phenolics was observed.

PMID- 20058929
TI  - Thermal chemistry of methylene- and phenyl-functionalized carbon nanotubes.
AB  - Thermal desorption of covalently functionalized SWNT was followed using Raman, X
      ray photoemission (XPS), and thermodesorption (TDS) spectroscopies. By
      functionalizing different sources of SWNT, we assess the thermal stability of
      phenyl- and methylene-SWNT derivatives in relation to the source diameter and
      helicity distribution. For all samples, broad desorption features were observed
      at approximately 600 K for the phenyl-SWNT and at approximately 500 K for the
      methylene-SWNT derivatives. In both cases, no influence on helicity and on
      diameter was observed for the range studied. The study shows that the stability
      of methylene addends on SWNT is inferior to that of the phenyl and proves that
      the main desorption pathway of phenyl addends is a phenyl-phenyl coupling
      reaction.

PMID- 20058930
TI  - Development of a mechanism for nitrate photochemistry in snow.
AB  - A reaction mechanism to reproduce photochemical processes in the snow is
      reported. We developed a box model to represent snow chemistry. Constrained by
      laboratory experiments carried out with artificial snow, we deduced first a
      reaction mechanism for N-containing species including 13 reactions. An
      optimization tool was developed to adjust systematically unknown photolysis rates
      of nitrate and nitrite (NO(2)(-)) and transfer rates of nitrogen oxides from the
      snow to the gas phase resulting in an optimum fit with respect to the
      experimental data. Further experiments with natural snow samples are presented,
      indicating that NO(2)(-) concentrations were much lower than in the artificial
      snow experiments. These observations were used to extend the reaction mechanism
      into a more general scheme including hydrogen peroxide (H(2)O(2)) and
      formaldehyde (HCHO) chemistry leading to a set of 18 reactions. The simulations
      indicate the importance of H(2)O(2) and HCHO as either a source or sink of
      hydroxyl radicals in the snow photochemistry mechanism. The addition of H(2)O(2)
      and HCHO in the mechanism allows the reproduction of the observed low NO(2)(-)
      concentration.

PMID- 20058931
TI  - Asymmetric mannich reaction of malonates with imines catalyzed by a chiral
      calcium complex.
AB  - A chiral calcium complex was found to be effective for the Mannich reactions of
      malonates with N-Boc imines. The desired adducts were obtained in excellent
      yields (up to 95%) with moderate to good enantioselectivities (up to 77% ee).

PMID- 20058932
TI  - Modification of poly(lactic/glycolic acid) surface by chemical attachment of
      poly(ethylene glycol).
AB  - Biodegradable polyesters such poly(lactic acid) and poly(lactic/glycolic acid)
      (PLGA) copolymers are preferred biomaterials and used among others as drug
      delivery systems, although their surface hydrophobicity limits their application.
      In this work, chemical modification of the PLGA surface was developed by coupling
      of either linear or starlike poly(ethylene glycol) (PEG) molecules via chemical
      bonds to the PLGA surface following amino functionalization as a first step to
      improve its biocompatibility. The chemical attachment was followed by detailed X
      ray photoelectron spectroscopy (XPS) studies. It was shown that substantial
      modification can be achieved by linear PEG, but even higher surface coverage with
      hydrophilic groups can be obtained when the six-armed PEG is applied with the
      additional advantage of possible further functionalization via free amino groups
      available on the surface of the latter. As a final goal, a significant increase
      of water wettability together with reduced protein adsorption was achieved on PEG
      coupled PLGA surfaces.

PMID- 20058933
TI  - Cytotoxic acylphloroglucinol derivatives from the twigs of Garcinia cowa.
AB  - An unusual polyprenylated acylphloroglucinol derivative unsubstituted at C-2 and
      C-6, garcicowin A (1), together with three other new (garcicowins B-D, 2-4) and
      nine known analogues, was isolated and characterized from the twigs of Garcinia
      cowa. The structures of 1-4 were elucidated by interpretation of their
      spectroscopic data. The compounds isolated were evaluated for their cytotoxicity
      against two cancer cell lines (HT-29 and HCT116) and against normal colon cells
      (CCD-18Co), and the results demonstrated their selective toxicity toward the
      cancer cells.

PMID- 20058934
TI  - Saponins and polyphenols from Fadogia ancylantha (makoni tea).
AB  - Three new saponins (1-3) and a known saponin, together with four known
      polyphenolic compounds, have been isolated from the fermented and dried leaves of
      Fadogia ancylantha (Makoni tea). The structures of compounds 1-3 were established
      by analysis of their spectroscopic data. Both an ethanol-water extract of F.
      ancylantha and its phenolic constituents showed significant free-radical
      scavenging and antimicrobial activities. No cytotoxicity, as evaluated by
      analysis of hypodiploid nuclei in HUVEC cells using propidium iodide staining,
      was observed for either the plant crude extract or its constituents.

PMID- 20058935
TI  - Synthesis and conformational characteristics of nonsymmetric pillar[5]arene.
AB  - A new nonsymmetric pillar[5]arene of ethoxymethoxypillar[5]arene
      (EMpillar[5]arene) has been synthesized. By 2D ROESY analysis of
      EMpillar[5]arene, the ethoxy and methoxy moieties were completely separated at
      the upper and lower rims, respectively. Moreover, by the variable-temperature
      (1)H NMR measurements of EMpillar[5]arene, the rotational movement of phenolic
      units in EMpillar[5]arene was slow on the NMR time scale or did not occur.

PMID- 20058936
TI  - Simulation of spontaneous substrate binding revealing the binding pathway and
      mechanism and initial conformational response of GlpT.
AB  - Glycerol 3-phosphate transporter (GlpT) mediates the import of glycerol 3
      phosphate (G3P) using the gradient of inorganic phosphate (P(i)). To study the
      process and mechanism of substrate binding and to investigate the protein's
      initial response, we performed equilibrium simulations of wild-type GlpT and
      several of its mutant forms in membranes in the presence of all physiologically
      relevant substrates (P(i)(-), P(i)(2-), G3P(-), and G3P(2-)). The simulations
      capture spontaneous substrate binding of GlpT, driven by the positive
      electrostatic potential of the lumen. K80 is found to act as a "hook" making the
      first encounter with the substrate and guiding it toward the binding site, where
      it binds tightly to R45, a key binding site residue that acts as a "fork" holding
      the substrate. R269 establishes no direct contact with the substrate during the
      simulations, a surprising behavior given its structural pseudosymmetry to R45. In
      all substrate-bound systems, partial closing of the cytoplasmic half of GlpT was
      observed. The substrate appears to stabilize the partially occluded state, as in
      the two apo simulations either no closing was observed or the protein reverted to
      its open form toward the end of the simulation, whereas in all substrate-bound
      systems, a stable partially closed state was produced. Along with the modulation
      of the periplasmic salt bridge network, these substrate-induced events
      destabilize the periplasmic half while inducing a closure in the cytoplasmic
      half, thus capturing the early stages of the proposed rocker-switch mechanism in
      GlpT.

PMID- 20058937
TI  - Effect of the hydrophobicity to net positive charge ratio on antibacterial and
      anti-endotoxin activities of structurally similar antimicrobial peptides.
AB  - The interaction between host-defense antimicrobial peptides (AMPs) and the
      bacterial lipopolysaccharide (LPS) governs both the susceptibility of the
      bacteria to the peptide and the ability of the peptide to inhibit LPS activation
      of immune cells. Both functions depend on the biophysical properties of the
      peptides. However, the sequence and structural diversity of AMPs makes it
      difficult to determine common denominators required for antimicrobial and LPS
      neutralizing activities. Toward this end, we synthesized and investigated a
      series of nine 12-amino acid peptides and their fatty acid-conjugated analogues
      composed of both D- and L-isomers of Leu and Lys at various ratios. The positions
      of the D-amino acids were preserved. These peptides differ in their net positive
      charge and hydrophobicity. However, their overall structure in the membrane is
      similar, as determined by Fourier transform infrared spectroscopy. The peptides
      and their analogues were functionally tested for their antibacterial and
      hemolytic activity, their ability to permeate LPS vesicles, their ability to
      neutralize LPS activation of macrophages, and their effect on LPS morphology,
      determined by negative staining electron microscopy. The data revealed that
      increasing the ratio between hydrophobicity and the net positive charge increases
      both antimicrobial and LPS neutralization activities, but with different modes of
      contributions. Whereas antimicrobial activity increases linearly with the
      increase in the peptides' hydrophobicity, peptides with different
      hydrophobicities are endowed with similar LPS neutralizing activities. Besides
      adding important information regarding AMP parameters involved in antimicrobial
      and anti-LPS activities, this study suggests the use of such diastereomers as
      potential templates for the development of simple molecules that conduct both
      types of functions.

PMID- 20058938
TI  - Degradation and adsorption characteristics of PHB depolymerase as revealed by
      kinetics of mutant enzymes with amino acid substitution in substrate-binding
      domain.
AB  - Extracelluar Poly[(R)-3-hydroxybutyrate] (PHB) depolymerase (PhaZ(RpiT1)) from
      Ralstonia pickettii T1 adsorbs to PHB surface via its substrate-binding domain
      (SBD) to enhance PHB degradation. Our previous study combining PCR random
      mutagenesis with the determination of PHB degradation levels of mutant enzymes
      suggested that Ser, Tyr, Val, Ala, and Leu residues in SBD are probably involved
      in the enzymatic adsorption to and degradation of PHB. In the present study, the
      effects of mutations at Leu441, Tyr443, and Ser445 on PHB degradation were
      investigated because these residues were predicted to form a beta-sheet structure
      and orient in the same direction to interact possibly directly with the PHB
      surface. Purified L441H, Y443H, and S445C mutant enzymes were prepared, and their
      CD spectra and hydrolytic activities for water-soluble substrates were found to
      be identical to those of wild-type enzyme, indicating that these mutations have
      no influence on their structures and their ability to cleave the ester bond. In
      contrast, the PHB-degrading activity of these mutants differed from that of the
      wild type: L441H and Y443H enzymes had lower PHB-degrading activity than their
      wild-type counterpart, whereas S445C had higher activity. Kinetic analysis of PHB
      degradation by the mutants suggested that the hydrophobic residues at these
      positions are important for the enzyme adsorption to the PHB surface, and such
      substitutions as Y443H and S445C may more effectively disrupt the PHB surface to
      enhance the hydrolysis of PHB polymer chains than the wild-type enzyme. Surface
      plasmon resonance (SPR) analysis revealed that the three substitutions mentioned
      above altered the association phase rather than the dissociation phase in the
      enzyme adsorption to the polymer surface.

PMID- 20058939
TI  - Chiral recognition in cinchona alkaloid protonated dimers: mass spectrometry and
      UV photodissociation studies.
AB  - Chiral recognition in protonated cinchona alkaloid dimers has been studied in
      mass spectrometry experiments. The experimental setups involved a modified 7T FT
      ICR (Fourier transform-ion cyclotron resonance) mass spectrometer (MS) and a
      modified Paul ion trap both equipped with an electrospray ionization source
      (ESI). The Paul ion trap has been coupled to a frequency-doubled dye laser. The
      fragmentation of protonated dimers made from cinchonidine (Cd) and the two
      pseudoenantiomers of quinine, namely, quinine (Qn) and quinidine (Qd), has been
      assessed by means of collision-induced dissociation (CID) as well as UV
      photodissociation (UVPD). Whereas CID fragmentation of the dimers only leads to
      the evaporation of the monomers, UVPD results in the additional loss of a neutral
      radical fragment corresponding to the quinuclidinyl radical. The effect of the
      excitation wavelength and of complexation with H(2)SO(4) has been studied to cast
      light on the reaction mechanism. Complexation with H(2)SO(4) modifies the
      photoreactivity of the dimers; only evaporation of the monomeric fragments,
      quinine, and cinchonidine is observed. Comparison between the mass spectra of the
      cinchona alkaloid (CdQnH(+)) or (CdQdH(+)) dimers resulting from the UVPD of
      (CdQnH(2)SO(4)H(+)) and that of bare (CdQnH(+)) helps propose a fragmentation
      mechanism, which is thought to involve fast proton transfer from the quinuclidine
      part of a molecular subunit to the quinoline ring. CID and UV fragmentation
      experiments show that the homochiral dimer is more strongly bound than the
      heterochiral adduct.

PMID- 20058940
TI  - Voice fundamental frequency modulates vocal response to pitch perturbations
      during English speech.
AB  - Previous research has demonstrated task-dependent vocal responses to pitch
      perturbations during speech production. The present study investigated the effect
      of voice fundamental frequency (F(0)) on the modulation of vocal responses during
      English speech. Randomized pitch shifts of +/-100 or 200 cents during speaking
      were presented to English speakers. Results indicated larger vocal responses and
      shorter latencies at a high voice F(0) than at a low voice F(0), but no
      significance differences were observed for stimulus magnitude or direction. These
      findings suggest that the pitch-shift reflex during speech can be modulated as a
      function of voice F(0).

PMID- 20058941
TI  - Multiple instances of vocal sensorimotor adaptation to frequency-altered feedback
      within a single experimental session.
AB  - Vocal sensory-motor adaptation is typically studied by introducing a prolonged
      change in auditory feedback. While it may be preferable to perform multiple
      blocks of adaptation within a single experiment, it is possible that a carry-over
      effect from previous blocks of adaptation may affect the results of subsequent
      blocks. Speakers were asked to vocalize an /a/ sound and match a target note
      during ten adaptation blocks. Each block represented a unique combination of
      target note and shift direction. The adaptation response was found to be similar
      for all blocks, indicating that there were no carry-over effects from previous
      blocks of adaptation.

PMID- 20058942
TI  - A method for finding constrictions in high front vowels.
AB  - The purpose of this study was to devise a consistent and robust method for
      defining vocal tract constrictions in high front vowels. A procedure was devised
      to find the length and position of the articulatory constriction in high front
      vowels that is not sensitive to local fluctuations in vocal tract shape and to
      the constriction-defining parameters. A method based on a visual examination of
      plots for constriction length and position as functions of the constriction
      defining parameters was found to provide stable constriction definitions.

PMID- 20058943
TI  - Post-transient shifts in auditory lateralization: effects of target level.
AB  - Exposing one ear to a series of brief 80 dB sound pressure level (SPL) inducing
      tones reduces the tendency to lateralize subsequent target tones to that ear and
      shifts the point of subjective equality (PSE) toward the unexposed ear.
      Furthermore, targets with average SPLs of 60 and 80 dB at the two ears showed
      similar changes in PSE. These results support and extend earlier findings of
      Arieh and Marks (2007). Percept. Psychophys. 69, 523-528 and suggest the presence
      of a mechanism, located at least partially before the site of binaural
      integration, that depresses the magnitude of intensity information from the ear
      in response to moderately intense transient stimuli. Assuming that lateralization
      depends on the ratio of the magnitude of intensity information from the two ears
      that reach the central integrator, the results imply that the inducer reduced the
      representations of magnitude of 60 and 80 dB test tones in equal proportion.

PMID- 20058944
TI  - The role of temporal fine structure in harmonic segregation through mistuning.
AB  - Bernstein and Oxenham [(2008). J. Acoust. Soc. Am. 124, 1653-1667] measured
      thresholds for discriminating the fundamental frequency, F0, of a complex tone
      that was passed through a fixed bandpass filter. They found that performance
      worsened when the F0 was decreased so that only harmonics above the tenth were
      audible. However, performance in this case was improved by mistuning the odd
      harmonics by 3%. Bernstein and Oxenham considered whether the results could be
      explained in terms of temporal fine structure information available at the output
      of a single auditory filter and concluded that their results did not appear to be
      consistent with such an explanation. Here, it is argued that such cues could have
      led to the improvement in performance produced by mistuning the odd harmonics.

PMID- 20058945
TI  - The effect of hearing-aid compression on judgments of relative distance.
AB  - The overall level of a sound is an important auditory cue to distance in rooms,
      but this cue might be affected adversely by the amplitude compression found in
      most modern hearing aids because this explicitly changes levels. This prediction
      was tested using a synthetic-distance design to measure the just-noticeable
      difference (JND) in distance from distances of 2 or 5 m. Twenty-six aided
      listeners participated. The results did not show any effect of compression ratio
      upon JNDs. A possible interpretation is that the listeners had acclimatized to
      the effect their aids have on level.

PMID- 20058946
TI  - Seismoelectric reflection and transmission at a fluid/porous-medium interface.
AB  - The dispersion relation for seismoelectric wave propagation in poroelastic media
      is formulated in terms of effective densities comprising all viscous and
      electrokinetic coupling effects. Using Helmholtz decomposition, two
      seismoelectric conversion coefficients are derived, for an incident P-wave upon
      an interface between a compressible fluid and a poroelastic medium. These
      coefficients relate the incident P-wave to a reflected electromagnetic wave in
      the fluid, and a transmitted electromagnetic wave in the porous medium. The
      dependency on angle of incidence and frequency is computed. Using orthodox and
      interference fluxes, it is shown that energy conservation is satisfied. A
      sensitivity analysis indicates that electrolyte concentration, viscosity, and
      permeability highly influence seismoelectric conversion.

PMID- 20058947
TI  - On Dowell's simplification for acoustic cavity-structure interaction and
      consistent alternatives.
AB  - A widely employed description of the acoustical response in a cavity whose walls
      are compliant, which was first proposed by Dowell and Voss [(1962). AIAA J. 1,
      476-477], uses the modes of the corresponding cavity with rigid walls as basis
      functions for a series representation of the pressure. It yields a velocity field
      that is not compatible with the movement of the boundary, and the system
      equations do not satisfy the principle of reciprocity. The simplified formulation
      is compared to consistent solutions of the coupled field equations in the time
      and frequency domains. In addition, this paper introduces an extension of the
      Ritz series method to fluid-structure coupled systems that satisfies all
      continuity conditions by imposing constraint equations to enforce any such
      conditions that are not identically satisfied by the series. A slender waveguide
      terminated by an oscillator is analyzed by each method. The simplified
      formulation is found to be very accurate for light fluid loading, except for the
      pressure field at frequencies below the fundamental rigid-cavity resonance,
      whereas the Ritz series solution is found to be extremely accurate in all cases.

PMID- 20058948
TI  - An iterative method for the computation of nonlinear, wide-angle, pulsed acoustic
      fields of medical diagnostic transducers.
AB  - The development and optimization of medical ultrasound transducers and imaging
      modalities require a computational method that accurately predicts the nonlinear
      acoustic pressure field. A prospective method should provide the wide-angle,
      pulsed field emitted by an arbitrary planar source distribution and propagating
      in a three-dimensional, large scale domain holding a nonlinear acoustic medium.
      In this paper, a method is presented that is free of any assumed wavefield
      directionality. The nonlinear acoustic wave equation is solved by treating the
      nonlinear term as a contrast source. This formulation leads to an iterative
      scheme that involves the repetitive solution of a linear wave problem through
      Green's function method. It is shown that accurate field predictions may be
      obtained within a few iterations. Moreover, by employing a dedicated numerical
      convolution technique, the method allows for a discretization down to two points
      per wavelength or period of the highest frequency of interest. The performance of
      the method is evaluated through a number of nonlinear field predictions for
      pulsed transducers with various geometries. The results demonstrate the
      directional independence of the method. Moreover, comparison with results from
      several existing methods shows that the method accurately predicts the nonlinear
      field for weak to moderate nonlinearity.

PMID- 20058949
TI  - Dislodgement and removal of dust-particles from a surface by a technique
      combining acoustic standing wave and airflow.
AB  - It is known that there are many fine particles on the moon and Mars. Their
      existence may cause risk for the success of a long-term project for NASA, i.e.,
      exploration and habitation of the moon and Mars. These dust-particles might cover
      the solar panels, making them fail to generate electricity, and they might also
      penetrate through seals on space suits, hatches, and vehicle wheels causing many
      incidents. The fine particles would be hazardous to human health if they were
      inhaled. Development of robust dust mitigation technology is urgently needed for
      the viable long-term exploration and habilitation of either the moon or Mars. A
      feasibility study to develop a dust removal technique, which may be used in space
      stations or other enclosures for habitation, is reported. It is shown
      experimentally that the acoustic radiation force produced by a 13.8 kHz 128 dB
      sound-level standing wave between a 3 cm-aperture tweeter and a reflector
      separated by 9 cm is strong enough to overcome the van der Waals adhesive force
      between the dust-particles and the reflector-surface. Thus the majority of fine
      particles (>2 microm diameter) on a reflector-surface can be dislodged and
      removed by a technique combining acoustic levitation and airflow methods. The
      removal efficiency deteriorates for particles of less than 2 microm in size.

PMID- 20058950
TI  - Finite amplitude method for measuring the nonlinearity parameter BA in small
      volume samples using focused ultrasound.
AB  - On the basis of finite amplitude and comparative methods, the acoustic
      nonlinearity parameter BA of a liquid sample of as small as 0.1 ml is measured
      using an 18.6-MHz focused Gaussian beam. The sample fills the space between a
      polystyrene plate and a tungsten reflector set about 1 mm apart from each other
      within the focal region. The sound speed c and attenuation coefficient alpha are
      determined using the time of flight and the insertion loss of the sound passing
      through the sample, respectively. The density rho is estimated from the
      reflection coefficient at the interface between the polystyrene plate and the
      sample, where the transformation from longitudinal to transverse waves is
      considered. To compensate for the effect of velocity dispersion on the second
      harmonic generation, the relative phase of the second harmonic sound is also
      measured using dual-frequency sound. By summarizing all the linear properties and
      amplitude data of the second harmonic component in the sound transmitted through
      the sample, the BA value is finally determined. The measurement is validated
      through the experiments on nondispersive liquids and weakly dispersive biological
      samples with known BA values.

PMID- 20058951
TI  - Effective fractional acoustic wave equations in one-dimensional random multiscale
      media.
AB  - This paper considers multiple scattering of waves propagating in a non-lossy one
      dimensional random medium with short- or long-range correlations. Using
      stochastic homogenization theory it is possible to show that pulse propagation is
      described by an effective deterministic fractional wave equation, which
      corresponds to an effective medium with a frequency-dependent attenuation that
      obeys a power law with an exponent between 0 and 2. The exponent is related to
      the Hurst parameter of the medium, which is a characteristic parameter of the
      correlation properties of the fluctuations of the random medium. Moreover the
      frequency-dependent attenuation is associated with a special frequency-dependent
      phase, which ensures that causality and Kramers-Kronig relations are satisfied.
      In the time domain the effective wave equation has the form of a linear integro
      differential equation with a fractional derivative.

PMID- 20058952
TI  - Broadband source localization using horizontal-beam acoustic intensity
      striations.
AB  - Waveguide invariant theory is applied to horizontal line array (HLA) beamformer
      output to localize moving broadband noise sources from measured acoustic
      intensity striation patterns. Acoustic signals emitted by ships of opportunity
      (merchant ships) were simultaneously recorded on a HLA and three hydrophones
      separated by 10 km during the RAGS03 (relationship between array gain and shelf
      break fluid processes) experiment. Hough transforms are used to estimate both the
      waveguide invariant parameter "beta" and the ratio of source range at the closest
      point of approach to source speed from the observed striation patterns. Broadband
      (50-150-Hz) acoustic data-sets are used to demonstrate source localization
      capability as well as inversion capability of waveguide invariant parameter beta.
      Special attention is paid to bathymetric variability since the acoustic intensity
      striation patterns seem to be influenced by range-dependent bathymetry of the
      experimental area. The Hough transform method is also applied to the HLA beam
      time record data and to the acoustic intensity data from three distant receivers
      to validate the estimation results from HLA beamformer output. Good agreement of
      the results from all three approaches suggests the feasibility of locating
      broadband noise sources and estimating waveguide invariant parameter beta in
      shallow waters.

PMID- 20058953
TI  - Geoacoustic inversions and localizations with adaptively beamformed data from a
      surface ship of opportunity source.
AB  - A technique has been developed for incorporating adaptively beamformed (ABF) data
      into geoacoustic inversions and source localizations based on matched-field
      processing. Rather than adaptively adjusting matched-field weights, for this
      paper ABF processing is applied to construct subaperture beam data from which the
      inversions and localizations are derived. This application of ABF processing to
      inversion and localization is successfully demonstrated with data collected on a
      horizontal line array from a surface ship of opportunity source (SSOS). When
      measured data representing noise from one or more interfering sources at various
      levels are injected into the data collected from the SSOS, the inversion
      processing with ABF subaperture data is successful at interferer noise levels
      exceeding the SSOS levels by 10-13 dB and for which the inversion processing with
      conventionally beamformed data fails.

PMID- 20058954
TI  - Observations and modeling of angular compression and vertical spatial coherence
      in sea surface forward scattering.
AB  - Measurements and modeling of spatial coherence and related angular spreading
      associated with forward scattering from the sea surface are presented. The
      measurements were taken in waters 80 m deep off the New Jersey coast in August
      2006. Acoustic signals from a source at depth 40 m were recorded on a vertical
      line array of length 1.4 m, centered at depth 25 m, and at range 200 m.
      Measurements in the 14-20-kHz frequency range are reported; the rms waveheight H
      was 0.16 m, setting kH as approximately 10 where k is acoustic wavenumber. A
      systematic study of measurements taken over four source-receiver bearing angles
      separated by 90 degrees suggests a null influence of changing bearing angle or
      equivalently directional wave effects. Sound speed was characterized by a
      downward-refracting profile. Refraction modifies the vertical angular spread due
      to rough sea surface scattering, which can be understood from Snell's law. The
      Snell mapping is smooth, so an approximation based on the mean grazing angle
      provides a functional relation between the angular variance near the surface and
      that at the receiver. The latter is measurably reduced owing to refraction, the
      effect called angular compression, and a parameter that quantifies this effect is
      defined.

PMID- 20058955
TI  - Low-frequency target strength and abundance of shoaling Atlantic herring (Clupea
      harengus) in the Gulf of Maine during the Ocean Acoustic Waveguide Remote Sensing
      2006 Experiment.
AB  - The low-frequency target strength of shoaling Atlantic herring (Clupea harengus)
      in the Gulf of Maine during Autumn 2006 spawning season is estimated from
      experimental data acquired simultaneously at multiple frequencies in the 300-1200
      Hz range using (1) a low-frequency ocean acoustic waveguide remote sensing
      (OAWRS) system, (2) areal population density calibration with several
      conventional fish finding sonar (CFFS) systems, and (3) low-frequency
      transmission loss measurements. The OAWRS system's instantaneous imaging diameter
      of 100 km and regular updating enabled unaliased monitoring of fish populations
      over ecosystem scales including shoals of Atlantic herring containing hundreds of
      millions of individuals, as confirmed by concurrent trawl and CFFS sampling. High
      spatial-temporal coregistration was found between herring shoals imaged by OAWRS
      and concurrent CFFS line-transects, which also provided fish depth distributions.
      The mean scattering cross-section of an individual shoaling herring is found to
      consistently exhibit a strong, roughly 20 dB/octave roll-off with decreasing
      frequency in the range of the OAWRS survey over all days of the roughly 2-week
      experiment, consistent with the steep roll-offs expected for sub-resonance
      scattering from fish with air-filled swimbladders.

PMID- 20058956
TI  - Spatial and temporal patterns of Risso's dolphin echolocation in the Southern
      California Bight.
AB  - Geographical and temporal trends in echolocation clicking activity can lead to
      insights into the foraging and migratory behaviors of pelagic dolphins. Using
      autonomous acoustic recording packages, the geographical, diel, and seasonal
      patterns of Risso's dolphin (Grampus griseus) echolocation click activity are
      described for six locations in the Southern California Bight between 2005 and
      2007. Risso's dolphin echolocation click bouts are identified based on their
      unique spectral characteristics. Click bouts were identified on 739 of 1959
      recording days at all 6 sites, with the majority occurring at nearshore sites. A
      significant diel pattern is evident in which both hourly occurrences of click
      bouts and click rates are higher at night than during the day. At all nearshore
      sites, Risso's dolphin clicks were identified year-round, with the highest daily
      occurrence at the southern end of Santa Catalina Island. Seasonal and interannual
      variabilities in occurrence were high across sites with peak occurrence in autumn
      of most years at most sites. These results suggest that Risso's dolphins forage
      at night and that the southern end of Santa Catalina Island represents an
      important habitat for Risso's dolphins throughout the year.

PMID- 20058957
TI  - Localization of sperm whales in a group using clicks received at two separated
      short baseline arrays.
AB  - In this paper, a sperm whale click analysis scheme is proposed in order to
      calculate the position of individual sperm whales in a group using data received
      at two arrays deployed near the surface. The proposed method mainly consists of
      two parts: short baseline (SBL) with classification and long baseline (LBL) with
      class matching. In SBL with classification, a click is automatically detected,
      and its direction of arrival is calculated. The clicks are then classified based
      on their direction vectors. The class data are then sent together with direction
      data and matched to the other array's class data. LBL with class matching is used
      for localization. The classification algorithm can be used to estimate the number
      of whales clicking and to list potential candidates for LBL matching. As a
      result, the proposed method is able to localize the positions of the whales in a
      group. The performance of the proposed method is evaluated using data recorded
      off Ogasawara islands with two arrays near the surface. The three-dimensional
      underwater trajectories of six sperm whales are extracted to demonstrate the
      capability of the proposed method.

PMID- 20058958
TI  - Experimental validation of a time domain simulation of high frequency ultrasonic
      propagation in a suspension of rigid particles.
AB  - Ultrasonic propagation in suspensions of particles is a difficult problem due to
      the random spatial distribution of the particles. Two-dimensional finite
      difference time domain simulations of ultrasonic propagation in suspensions of
      polystyrene 5.3 mum diameter microdisks are performed at about 50 MHz. The
      numerical results are compared with the Faran model, considering an isolated
      microdisk, leading to a maximum difference of 15% between the scattering cross
      section values obtained analytically and numerically. Experiments are performed
      with suspensions in through transmission and backscattering modes. The
      attenuation coefficient at 50 MHz (alpha), the ultrasonic velocity (V), and the
      relative backscattered intensity (I(B)) are measured for concentrations from 2 to
      25 mg/ml, obtained by modifying the number of particles. Each experimental
      ultrasonic parameter is compared to numerical results obtained by averaging the
      results derived from 15 spatial distributions of microdisks. alpha increases with
      the concentration from 1 to 17 dB/cm. I(B) increases with concentration from 2 to
      16 dB. The variation of V versus concentration is compared with the numerical
      results, as well as with an effective medium model. A good agreement is found
      between experimental and numerical results (the larger discrepancy is found for
      alpha with a difference lower than 2.1 dB/cm).

PMID- 20058959
TI  - Efficient frequency-domain finite element modeling of two-dimensional
      elastodynamic scattering.
AB  - A frequency-domain finite element technique is presented that enables the
      complete characterization of a finite-sized scatterer using a minimum number of
      separate model executions and a relatively small spatial modeling domain. The
      technique is implemented using a commercial finite element package. A certain
      forcing profile is applied at a set of points surrounding the scatterer to cause
      a uni-modal plane wave to be incident on the scatterer from a specified
      direction. The scattered field is recorded and decomposed first into modes and
      then into far-field scattering coefficients in different directions. The data
      obtained from the model are represented in a scattering matrix that describes the
      far-field scattering response for all combinations of incident and scattering
      angles. The information in the scattering matrix can be efficiently represented
      in the Fourier domain by another matrix containing a finite number of Fourier
      coefficients. It is shown how the complete scattering behavior in both the near-
      and far-field can be extracted from the matrix of Fourier coefficients. Modeling
      accuracy is examined in various ways, including a comparison with the analytical
      solution for a circular cavity, and guidelines for the selection of modeling
      parameters are given.

PMID- 20058960
TI  - Simplified expressions of the subtracted Kramers-Kronig relations using the
      expanded forms applied to ultrasonic power-law systems.
AB  - The Kramers-Kronig (KK) relations are a large class of integral transformations
      that exploit the broad principle of simple causality in order to link the
      physical properties of matter and materials. In applications to the complex
      valued wavenumber for acoustic propagation, the method of subtractions is used to
      form convergent integral relations between the phase velocity and the attenuation
      coefficient. When the method of subtractions is applied in the usual manner, the
      integrands in the relations become unnecessarily complicated. In this work, an
      expanded form of the subtracted relations is presented, which is essentially a
      truncated Taylor series expansion of the Hilbert transforms. The implementation
      of the relations only requires the explicit evaluation of two simply expressed
      integrals involving the Hilbert transform kernel. These two integrals determine
      the values of the other terms in the subtracted relations, demonstrating the
      computational efficiency of the technique. The method is illustrated analytically
      through its application to power-law attenuation coefficients and its associated
      dispersion, which are observed in a wide variety of materials. This approach
      explicitly shows the central role of the Hilbert transform kernel in the KK
      relations, which can become obscured in other formulations.

PMID- 20058961
TI  - Sound velocities and thermodynamic properties of water to 700 MPa and -10 to 100
      degrees C.
AB  - Sound velocities in liquid water were measured by the method of impulsive
      stimulated scattering in a sapphire-windowed high-pressure cell from -10 to 100
      degrees C and pressures as high as 700 MPa. Velocity measurements are compared
      with previous experimental efforts relative to the International Association for
      the Properties of Water and Steam (IAPWS-95) formulation for the equations of
      state. At 0 and -10 degrees C, sound velocities are in agreement with the one
      previously published study at sub-zero temperatures to 350 MPa. At ambient and
      elevated temperatures, differences between the present measurements and IAPWS-95
      velocities approach 0.5% near 700 MPa. Inversion of velocity data for density
      yields results within IAPWS-95 uncertainties, except at the highest temperatures,
      where elevated sound velocity at high pressure corresponds to as much as -0.2%
      disagreement with IAPWS-95.

PMID- 20058962
TI  - Experimental and theoretical study of acoustic waves generated by a laser line
      pulse in an optically absorptive isotropic cylinder.
AB  - The generation of acoustic waves by a line-focused laser pulse in an optically
      absorptive cylinder is studied experimentally and theoretically. Experiments are
      performed on a 5 mm diameter NG5 colored glass rod using Nd:yttrium aluminum
      garnet laser, which delivers 5 ns pulses. The numerical simulation is based on
      the semi-analytical model of a radially distributed thermoelastic source, which
      takes into account penetration of laser energy into the bulk of the sample. Good
      agreement between the experimental and calculated wave forms is observed.
      Comparison of these wave forms with an auxiliary simulation, which assumes the
      model of a dipole source located at the cylinder surface, reveals the effect of
      optical penetration on the shape of the wave form and also on the relative
      amplitude of bulk and surface waves.

PMID- 20058963
TI  - Analytical study of the acoustic field in a spherical resonator for single bubble
      sonoluminescence.
AB  - The acoustic field in the liquid within a spherical solid shell is calculated.
      The proposed model takes into account Stoke's wave equation in the viscous fluid,
      the membrane theory to describe the solid shell motion and the energy loss
      through the external couplings of the system. A point source at the resonator
      center is included to reproduce the acoustic emission of a sonoluminescence
      bubble. Particular calculations of the resulting acoustic field are performed for
      viscous liquids of interest in single bubble sonoluminescence. The model reveals
      that in case of radially symmetric modes of low frequency, the quality factor is
      mainly determined by the acoustic energy flowing through the mechanical coupling
      of the resonator. Alternatively, for high frequency modes the quality factor is
      mainly determined by the viscous dissipation in the liquid. Furthermore, the
      interaction between the bubble acoustic emission and the resonator modes is
      analyzed. It was found that the bubble acoustic emission produces local maxima in
      the resonator response. The calculated amplitudes and relative phases of the
      harmonics constituting the bubble acoustic environment can be used to improve
      multi-frequency driving in sonoluminescence.

PMID- 20058964
TI  - Excitation and focusing of Lamb waves in a multilayered anisotropic plate.
AB  - The radiation of Lamb waves by an axisymmetric source on the surface of an
      anisotropic plate is investigated. An analytical expression of the Green's
      function, valid in the far field domain, is derived. This approximation shows
      that the anisotropy of the propagation medium induces a focusing of Lamb modes in
      some directions, which correspond to minima of the slowness. Numerical
      simulations and experiments demonstrate that for the fundamental A(0) and S(0)
      modes, this phenomenon, analog to the phonon focusing effect, can be very strong
      in materials such as composite fiber-reinforced polymers. This effect due to the
      plate anisotropy must be correctly taken into account, for example, in order to
      develop systems for in situ structural health monitoring. The choice of the most
      appropriate Lamb mode, the excitation frequency, and the design of the array of
      piezoelectric disks used as transmitters and receivers depends on such
      considerations.

PMID- 20058965
TI  - Extracting guided waves from cross-correlations of elastic diffuse fields:
      applications to remote structural health monitoring.
AB  - Due to their apparent complexity, diffuse fields are not commonly used by
      conventional structural health monitoring methodologies. However, recent
      theoretical and experimental studies have demonstrated that local Green's
      functions (GFs) can be estimated from the cross-correlation of elastic diffuse
      fields (CDFs) recorded between any points of a sensor grid and generated by
      sources located remotely from the monitoring area. Hence, this CDF technique
      effectively transforming each measurement point into a virtual elastic source,
      thus allowing to measure the local structural response (or GF). Theoretical and
      experimental studies are conducted to assess the broadband performance of the CDF
      technique for the extraction of low-frequency coherent Lamb waves (4-90 kHz)
      propagating in a thin aluminum plate of complex geometry using a scanning laser
      Doppler vibrometer. The coherent signal-to-noise ratio and the accuracy of the
      phase and group velocity measurements of the coherent A(0) mode obtained from CDF
      are also measured to quantify the influence of the spatio-temporal
      characteristics of the recorded diffuse field, the number and spatial
      configuration of the remote ultrasonic sources, and the influence of incoherent
      measurement noise (e.g., sensor noise). In addition, a criterion to assess the
      emergence rate of late coherent coda arrivals from CDF is also formulated.

PMID- 20058966
TI  - Prediction of noise reduction through vehicle path rerouting.
AB  - Traffic noise, produced by moving vehicles, is described in terms of the day
      night average sound level L(dn) and the day-evening-night level L(den). Both
      levels depend on the path of noise sources, such as road vehicles or aircraft.
      Usually, noise source path is rectilinear. Substituting a circle arc of radius R
      for the straight path segment yields noise reduction
      DeltaL=DeltaL(dn)=DeltaL(den). Assuming that noise propagation is governed by
      geometrical spreading, air absorption, and ground effect, relationship between
      DeltaL and R is derived. For example, replacement of a straight road at the
      distance of 100 m with the road of radius R=270 m and the angle Phi=68 degrees
      yields the noise reduction of 4 dB. In the case of road traffic noise, the
      presented results seem to be a viable alternative to barrier construction.

PMID- 20058967
TI  - Optimum absorption and aperture parameters for realistic coupled volume spaces
      determined from computational analysis and subjective testing results.
AB  - This project utilizes computational modeling to study the effects of varying two
      architectural parameters, absorption ratio and aperture size, in a realistic
      coupled volume concert hall. Coupled volumes have been shown to exhibit non
      exponential sound energy decay profiles, referred to as double slope effect. A
      number of objective metrics (T30/T15, LDT/T10, decay ratio, and DeltaL) have been
      used to quantify the double slope effect of the profiles generated in the virtual
      hall. T30/T15 and LDT/T10 showed similar trends across all hall configurations,
      indicating decreasing double slope effect with increasing coupled volume
      absorption ratio for each aperture size, and producing highest values at a
      specific aperture size for each absorption ratio. Generally, LDT/T10 provides
      finer resolution than T30/T15 when analyzing the decay profiles in this study.
      Results from the two metrics derived from Bayesian analysis, decay ratio and
      DeltaL, seem less consistent. Subjective testing has also been conducted to
      determine the effect of varying the two architectural parameters in the hall, and
      multidimensional scaling analysis shows that, in general, listener preference is
      inversely proportional to the level of double slope effect, with the highest
      levels of preference occurring at low and medium levels of double slope effect.
      Recommended design guidelines for coupled volume halls are provided based on
      these computational and subjective results.

PMID- 20058968
TI  - The ensemble variance of pure-tone measurements in reverberation rooms.
AB  - Reverberation rooms are often used for measuring the sound power emitted by
      sources of sound. At medium and high frequencies, where the modal overlap is
      high, a fairly simple model based on sums of waves from random directions having
      random phase relations gives good predictions of the ensemble statistics of
      measurements in such rooms. Below the Schroeder frequency, the relative variance
      is much larger, particularly if the source emits a pure-tone. The established
      theory for this frequency range is based on ensemble statistics of modal sums and
      requires knowledge of mode shapes and the distribution of modal frequencies. This
      paper extends the far simpler random wave theory to low frequencies. The two
      theories are compared, and their predictions are found to compare well with
      experimental and numerical results.

PMID- 20058969
TI  - Sound absorption of a micro-perforated panel backed by an irregular-shaped
      cavity.
AB  - In the pursuit of more effective noise control devices, the cavity backed micro
      perforated panel absorber (CBMPPA) is developed in this study. A CBMPPA differs
      from the conventional micro-perforated panel (MPP) absorber in that the MPP is
      backed by a trapezoidal cavity, which allows more effective vibroacoustic
      coupling between the MPP and the cavity. A two-dimensional theoretical model is
      established and tested both numerically and experimentally. Based on the verified
      theoretical model, sound absorption performance of a trapezoidal CBMPPA is
      investigated numerically. Results show that the shape of the backing cavity can
      significantly alter the sound absorption mechanisms and frequency distribution of
      overall sound absorption coefficient of the absorber. Further analyses show that
      acoustic modes that are initially decoupled from the MPP in the rectangular
      configuration are coupled with the air motion in the MPP, which accounts for the
      change in absorption pattern of the trapezoidal CBMPPA. By the same token, it
      also provides the flexibility for tuning the effective absorption range of the
      absorber. Due to the varying impedance matching conditions, the absorption
      performance of the trapezoidal CBMPPA exhibits obvious local characteristics over
      the MPP surface, which contrasts with the spatially uniform absorption in the
      conventional MPP absorber.

PMID- 20058970
TI  - Suitable reverberation times for halls for rock and pop music.
AB  - The existing body of literature regarding the acoustic design of concert halls
      has focused almost exclusively on classical music, although there are many more
      performances of popular music, including rock and pop. Objective measurements
      were made of the acoustics of 20 rock music venues in Denmark and a questionnaire
      was used in a subjective assessment of those venues with professional rock
      musicians and sound engineers as expert listeners. Correlations between the
      measurements show that clarity, including bass frequencies down to 63 Hz, is
      important for the general impression of the acoustics of the hall. The best-rated
      halls in the study have reverberation times that are approximately frequency
      independent from 0.6 to 1.2 s for hall volumes from 1000 to 6000 m(3). The worst
      rated halls in the study had significantly higher reverberation times in the 63
      and 125 Hz bands. Since most audiences at rock concerts are standing, absorption
      coefficients were measured with a standing audience from 63 Hz to 4 kHz. These
      measurements showed that a standing audience absorbs about five times as much
      energy in mid-/high-frequency bands as in low-frequency bands.

PMID- 20058971
TI  - Evaluation of a method for the measurement of subwoofers in usual rooms.
AB  - This paper evaluates the potential of the field separation method (FSM) for
      performing subwoofer measurements in a small test room with poor absorbing
      properties, as is commonly available. The FSM requires the knowledge of both
      acoustic pressure and velocity fields on a closed surface surrounding the tested
      source. Pressures and velocities, measured using a p-p probe on a half-sphere
      mesh, are collected under various conditions: in a room with variable
      reverberation time (6.4-0.6 s) and with four measurement half-sphere radii. The
      measured data are expanded on spherical harmonics, separating outward and inward
      propagation. The pressure field reflected by walls of the surrounding room is
      then subtracted from the measured field to estimate the pressure field that would
      have been radiated under free-field conditions. Theoretical frequency response of
      the subwoofer is computed using an analytical formulation derived from an
      extended Thiele and Small model of the membrane motion, coupled to a boundary
      element model for computing the radiated pressure while taking into account the
      actual subwoofer geometry. Measurement and simulation results show a good
      agreement. The effects of the measurement distance, the measurement point number,
      and the room reverberation time on the separation process are then discussed.

PMID- 20058972
TI  - Full bandwidth calibration procedure for acoustic probes containing a pressure
      and particle velocity sensor.
AB  - Calibration of acoustic particle velocity sensors is still difficult due to the
      lack of standardized sensors to compare with. Recently it is shown by Jacobsen
      and Jaud [J. Acoust. Soc. Am. 120, 830-837 (2006)] that it is possible to
      calibrate a sound pressure and particle velocity sensor in free field conditions
      at higher frequencies. This is done by using the known acoustic impedance at a
      certain distance of a spherical loudspeaker. When the sound pressure is measured
      with a calibrated reference microphone, the particle velocity can be calculated
      from the known impedance and the measured pressure. At lower frequencies, this
      approach gives unreliable results. The method is now extended to lower
      frequencies by measuring the acoustic pressure inside the spherical source. At
      lower frequencies, the sound pressure inside the sphere is proportional to the
      movement of the loudspeaker membrane. If the movement is known, the particle
      velocity in front of the loudspeaker can be derived. This low frequency approach
      is combined with the high frequency approach giving a full bandwidth calibration
      procedure which can be used in free field conditions using a single calibration
      setup. The calibration results are compared with results obtained with a standing
      wave tube.

PMID- 20058973
TI  - Design of an efficient music-speech discriminator.
AB  - In this paper, the problem of the design of a simple and efficient music-speech
      discriminator for large audio data sets in which advanced music playing
      techniques are taught and voice and music are intrinsically interleaved is
      addressed. In the process, a number of features used in speech-music
      discrimination are defined and evaluated over the available data set.
      Specifically, the data set contains pieces of classical music played with
      different and unspecified instruments (or even lyrics) and the voice of a teacher
      (a top music performer) or even the overlapped voice of the translator and other
      persons. After an initial test of the performance of the features implemented, a
      selection process is started, which takes into account the type of classifier
      selected beforehand, to achieve good discrimination performance and computational
      efficiency, as shown in the experiments. The discrimination application has been
      defined and tested on a large data set supplied by Fundacion Albeniz, containing
      a large variety of classical music pieces played with different instrument, which
      include comments and speeches of famous performers.

PMID- 20058974
TI  - Intelligibility and listener preference of telephone speech in the presence of
      babble noise.
AB  - Two procedures for improving the intelligibility of wideband telephone speech in
      the presence of competing babble noise are evaluated. One procedure is
      differentiation, the other consists of equalizing the speech spectrum by applying
      the inverse of the average spectrum of formant amplitudes for adult male speakers
      ("formant equalization"). Speech processed by these two methods was evaluated
      both for intelligibility and for listener preference. Both methods produced a
      clear increase in intelligibility compared to unprocessed wideband telephone
      speech. Formant equalization was found to be preferred over differentiation, more
      so at low signal-to-noise ratios than at high ones.

PMID- 20058975
TI  - A different approach to use narrowband super-resolution multiple signal
      classification algorithm on wideband sources.
AB  - There are varieties of wideband direction-of-arrival (DOA) estimation algorithms.
      Their structure comprises a number of narrowband ones, each performs in one
      frequency in a given bandwidth, and then different responses should be combined
      in a proper way to yield true DOAs. Hence, wideband algorithms are always complex
      and so non-real-time. This paper investigates a method to derive a flat response
      of narrowband multiple signal classification (MUSIC) [R. O. Schmidt, IEEE Trans.
      Antennas Propag., 34, 276-280 (1986)] algorithm in the whole frequencies of given
      band. Therefore, required conditions of applying narrowband algorithm on wideband
      impinging signals will be given through a concrete analysis. It could be found
      out that array sensor locations are able to compensate the frequency variations
      to reach a flat response of DOAs in a specified wideband frequency.

PMID- 20058976
TI  - Distribution theory approach to implementing directional acoustic sensors.
AB  - The objective of directional acoustic sensors is to provide high directivity
      while occupying a small amount of space. An idealized point sensor achieves this
      objective from a knowledge of the spatial partial derivatives of acoustic
      pressure at a point in space. Direct measurement of these derivatives is
      difficult in practice. Consequently, it is expedient to come up with indirect
      methods. The use of pressure sensors to construct finite-difference
      approximations is an example of such a method. This paper utilizes the theory of
      distributions to derive another indirect method for estimating the various
      spatial partial derivatives of the pressure. This alternate method is then used
      to construct a multichannel filter which processes the acoustic pressure by mean
      of three-dimensional integral transforms throughout a 6epsilon-length cube
      centered at the origin. The output of the multichannel filter is a spatially and
      temporally filtered version of the pressure at the origin. The temporal filter is
      a lowpass Gaussian filter whose bandwidth is inversely proportional to epsilon.
      Finally, the lattice method for numerical multiple integration is utilized to
      develop a discrete-spatial version of the multichannel filter.

PMID- 20058977
TI  - Reconstruction of radiating sound fields using minimum energy method.
AB  - A method for reconstructing a pressure field at the surface of a radiating body
      or source is presented using recording data of a microphone array. The radiation
      is assumed to consist of many spherical radiators, as microphone positions are
      present in the array. These monopoles are weighted using a parameter alpha, which
      broadens or narrows the overall radiation directivity as an effective and highly
      intuitive parameter of the radiation characteristics. A radiation matrix is built
      out of these weighted monopole radiators, and for different assumed values of
      alpha, a linear equation solver reconstructs the pressure field at the body's
      surface. It appears that from these many arbitrary reconstructions, the correct
      one minimizes the reconstruction energy. The method is tested, localizing the
      radiation points of a Balinese suling flute, reconstructing complex radiation
      from a duff frame drum, and determining the radiation directivity for the first
      seven modes of an Usbek tambourine. Stability in terms of measurement noise is
      demonstrated for the plain method, and additional highly effective algorithm is
      added for a noise level up to 0 dB. The stability of alpha in terms of minimal
      reconstruction energy is shown over the whole range of possible values for alpha.
      Additionally, the treatment of unwanted room reflections is discussed, still
      leading to satisfactory results in many cases.

PMID- 20058978
TI  - Short pulse multi-frequency phase-based time delay estimation.
AB  - An approach for time delay estimation, based on phase difference detection, is
      presented. A multiple-frequency short continuous wave pulse is used to solve the
      well-known phase ambiguity problem when the maximum distance exceeds a full
      wavelength. Within an unambiguous range defined with the lowest frequency
      difference between components, the corresponding phase difference is unique and
      any distance within this range can be determined. Phase differences between
      higher frequency components are used to achieve a finer resolution. The concept
      will be presented and the effectiveness of the approach will be investigated
      through theoretical and practical examples. The method will be validated using
      underwater acoustic measurements, simulating noisy environments, demonstrating
      resolutions better than a 50th of a wavelength, even in the presence of high
      levels (-5 dB) of additive Gaussian noise. Furthermore, the algorithm is simple
      to use and can be easily implemented, being based on phase detection using the
      discrete Fourier transform.

PMID- 20058979
TI  - Distortion product otoacoustic emission phase and component analysis in human
      newborns.
AB  - Apical distortion product otoacoustic emissions (DPOAEs) are comprised of at
      least two components, as evidenced by the interference pattern of alternating
      maxima and minima known as fine structure. DPOAE fine structure is produced by
      the shifting phase relationship in the ear canal, between the generator and
      characteristic frequency (CF) component of the response. Each component arises
      from a different cochlear region and, according to theory, reflects a distinct
      generation mechanism. The analysis of DPOAE components and phase in newborns may
      provide a window into targeted aspects of cochlear physiology during development.
      2f(1)-f(2) DPOAE fine structure was recorded from 15 adults and 14 newborns using
      a swept-tone technique. DPOAE group delay, as well as magnitude and phase of each
      component, was compared between age groups. Results show narrower fine structure
      spacing, a longer group delay (steeper phase gradient) in low frequencies, and a
      stronger relative contribution from the CF component in newborns. The prolonged
      group delay for low-frequency DPOAEs could indicate immature basilar membrane
      motion in the apex of the cochlea and warrants further investigation. The
      enhanced contribution from the CF component may have implications for clinical
      practice as well as for theories of cochlear maturation.

PMID- 20058980
TI  - Forward-masking patterns produced by symmetric and asymmetric pulse shapes in
      electric hearing.
AB  - Two forward-masking experiments were conducted with six cochlear implant
      listeners to test whether asymmetric pulse shapes would improve the place
      specificity of stimulation compared to symmetric ones. The maskers were either
      cathodic-first symmetric biphasic, pseudomonophasic (i.e., with a second anodic
      phase longer and lower in amplitude than the first phase), or "delayed
      pseudomonophasic" (identical to pseudomonophasic but with an inter-phase gap)
      stimuli. In experiment 1, forward-masking patterns for monopolar maskers were
      obtained by keeping each masker fixed on a middle electrode of the array and
      measuring the masked thresholds of a monopolar signal presented on several other
      electrodes. The results were very variable, and no difference between pulse
      shapes was found. In experiment 2, six maskers were used in a wide bipolar
      (bipolar+9) configuration: the same three pulse shapes as in experiment 1, either
      cathodic-first relative to the most apical or relative to the most basal
      electrode of the bipolar channel. The pseudomonophasic masker showed a stronger
      excitation proximal to the electrode of the bipolar pair for which the short,
      high-amplitude phase was anodic. However, no difference was obtained with the
      symmetric and, more surprisingly, with the delayed pseudomonophasic maskers.
      Implications for cochlear implant design are discussed.

PMID- 20058981
TI  - Temporal pitch percepts elicited by dual-channel stimulation of a cochlear
      implant.
AB  - McKay and McDermott [J. Acoust. Soc. Am. 100, 1081-1092 (1996)] found that when
      two different amplitude-modulated pulse trains are presented to two channels
      separated by <1.5 mm, some cochlear implant (CI) listeners perceive the aggregate
      temporal pattern. The present study attempted to extend this general finding and
      to test whether dual-electrode stimulation would increase the upper limit of
      temporal pitch perception in CIs. Six subjects were asked to rank 12 dual-channel
      stimuli differing in their rate [ranging from 92 to 516 pps (pulses per second)
      on each individual channel] and in their inter-channel delay (pulses on the two
      channels being either nearly simultaneous or delayed by half the period). The
      data showed that, for an electrode separation of 0.75 or 1.1 mm, (a) the
      perceived pitch was on average slightly higher for the long-delay than for the
      short-delay stimuli but never matched the pitch corresponding to the aggregate
      temporal pattern, (b) the upper limit of temporal pitch did not increase using
      long-delay stimuli, and (c) the pitch differences between short- and long-delay
      stimuli were largely insensitive to channel order and to electrode configuration.
      These results suggest that there may be more independence between CI channels
      than previously thought.

PMID- 20058982
TI  - Sensory constraints on auditory identification of the material and geometric
      properties of struck bars.
AB  - A computational formula is derived for estimating the constraints limited
      auditory sensitivity imposes on auditory identification of the material and
      geometric properties of struck bars. The formula combines a model of the
      transverse motion of the bar with empirical psychometric functions to map out
      "null" regions in the bar's physical parameter space where changes in the
      frequency, amplitude, and decay of partials are likely below threshold for
      detection. Parameters of the physical space include bar density, Young's modulus,
      fluid and viscoelastic damping factors, bar length, and bar cross-sectional area
      (as related to bar shape and hollowness). The formula is used to estimate the
      possible effect of limited sensitivity in past studies on the auditory
      identification of bar attributes. The results suggest that sensitivity may,
      indeed, have played a role in some studies, and that apparent discrepancies in
      results may be understood based on whether the predominant source of damping was
      internal or external to the bar. The formula identifies conditions representing
      an expected bound on identification performance and thereby may be used to aid in
      the design of future studies for which the struck bar is the sound source of
      choice.

PMID- 20058984
TI  - Computation of the head-related transfer function via the fast multipole
      accelerated boundary element method and its spherical harmonic representation.
AB  - The head-related transfer function (HRTF) is computed using the fast multipole
      accelerated boundary element method. For efficiency, the HRTF is computed using
      the reciprocity principle by placing a source at the ear and computing its field.
      Analysis is presented to modify the boundary value problem accordingly. To
      compute the HRTF corresponding to different ranges via a single computation, a
      compact and accurate representation of the HRTF, termed the spherical spectrum,
      is developed. Computations are reduced to a two stage process, the computation of
      the spherical spectrum and a subsequent evaluation of the HRTF. This
      representation allows easy interpolation and range extrapolation of HRTFs. HRTF
      computations are performed for the range of audible frequencies up to 20 kHz for
      several models including a sphere, human head models [the Neumann KU-100
      ("Fritz") and the Knowles KEMAR ("Kemar") manikins], and head-and-torso model
      (the Kemar manikin). Comparisons between the different cases are provided.
      Comparisons with the computational data of other authors and available
      experimental data are conducted and show satisfactory agreement for the
      frequencies for which reliable experimental data are available. Results show
      that, given a good mesh, it is feasible to compute the HRTF over the full audible
      range on a regular personal computer.

PMID- 20058983
TI  - The role of suppression in psychophysical tone-on-tone masking.
AB  - This study tested the hypothesis that suppression contributes to the difference
      between simultaneous masking (SM) and forward masking (FM). To obtain an
      alternative estimate of suppression, distortion-product otoacoustic emissions
      (DPOAEs) were measured in the presence of a suppressor tone. Psychophysical
      masking and DPOAE-suppression measurements were made in 22 normal-hearing
      subjects for a 4000-Hz signal/f(2) and two masker/suppressor frequencies: 2141
      and 4281 Hz. Differences between SM and FM at the same masker level were used to
      provide a psychophysical estimate of suppression. The increase in L(2) to
      maintain a constant output (L(d)) provided a DPOAE estimate of suppression for a
      range of suppressor levels. The similarity of the psychophysical and DPOAE
      estimates for the two masker/suppressor frequencies suggests that the difference
      in amount of masking between SM and FM is at least partially due to suppression.

PMID- 20058985
TI  - Prediction of binaural speech intelligibility against noise in rooms.
AB  - In the presence of competing speech or noise, reverberation degrades speech
      intelligibility not only by its direct effect on the target but also by affecting
      the interferer. Two experiments were designed to validate a method for predicting
      the loss of intelligibility associated with this latter effect. Speech reception
      thresholds were measured under headphones, using spatially separated target
      sentences and speech-shaped noise interferers simulated in virtual rooms. To
      investigate the effect of reverberation on the interferer unambiguously, the
      target was always anechoic. The interferer was placed in rooms with different
      sizes and absorptions, and at different distances and azimuths from the listener.
      The interaural coherence of the interferer did not fully predict the effect of
      reverberation. The azimuth separation of the sources and the coloration
      introduced by the room also had to be taken into account. The binaural effects
      were modeled by computing the binaural masking level differences in the studied
      configurations, the monaural effects were predicted from the excitation pattern
      of the noises, and speech intelligibility index weightings were applied to both.
      These parameters were all calculated from the room impulse responses convolved
      with noise. A 0.95-0.97 correlation was obtained between the speech reception
      thresholds and their predicted value.

PMID- 20058986
TI  - Effect of age at onset of deafness on binaural sensitivity in electric hearing in
      humans.
AB  - Sensitivity to binaural cues was studied in 11 bilateral cochlear implant users,
      all of whom received both of their cochlear implants as adults, but who varied in
      the age at onset of deafness, from pre-lingual to childhood-onset to adult-onset.
      Sensitivity to interaural timing difference (ITD) and interaural level difference
      (ILD) cues was measured at basal, middle, and apical pitch-matched places of
      stimulation along the cochlear arrays, using a stimulation rate of 100 Hz.
      Results show that there is a trend for people whose onset of deafness occurred
      during adult life or late childhood to retain at least some sensitivity to ITDs,
      whereas people with onset of deafness earlier in life were insensitive to ITDs.
      In contrast, ILD cue sensitivity was present in all subjects. There were no
      effects of place of stimulation on binaural sensitivity, suggesting that there is
      no indication of a dependence of ITD sensitivity on apical vs basal electrode
      location.

PMID- 20058987
TI  - A relation between electrode discrimination and amplitude modulation detection by
      cochlear implant listeners.
AB  - The objective of this study was to examine the relation between measures of
      spectral and temporal resolutions in cochlear implant listeners at a particular
      electrode location. The hypothesis was that a common underlying factor, such as
      the health of local groups of neurons, might partially determine patients'
      sensitivity to both spectral and temporal cues at specific tonotopic locations.
      Participants were adult cochlear implant listeners. A significant correlation was
      found between electrode discrimination measured at soft levels (20% and 30% of
      the dynamic range) and modulation sensitivity at those levels, for stimulation in
      bipolar mode and a 100 Hz modulation rate. Correlations between the two measures
      were weaker under monopolar stimulation, or when the modulation rate was 10 Hz.
      At a higher stimulation level (40% of the dynamic range), no significant
      correlations between these measures were observed. It is hypothesized that the
      more restricted excitation pattern at lower levels and/or with a narrower
      stimulation mode allows the measurement of locally driven sensitivity to spectral
      and temporal cues, particularly under more challenging listening conditions.
      Thus, psychophysical measures obtained under conditions that evoke a narrower
      excitation pattern may serve as a useful indicator of the functional health of
      local neural populations.

PMID- 20058988
TI  - On the importance of preserving the harmonics and neighboring partials prior to
      vocoder processing: implications for cochlear implants.
AB  - Pre-processing based noise-reduction algorithms used for cochlear implants (CIs)
      can sometimes introduce distortions which are carried through the vocoder stages
      of CI processing. While the background noise may be notably suppressed, the
      harmonic structure and/or spectral envelope of the signal may be distorted. The
      present study investigates the potential of preserving the signal's harmonic
      structure in voiced segments (e.g., vowels) as a means of alleviating the
      negative effects of pre-processing. The hypothesis tested is that preserving the
      harmonic structure of the signal is crucial for subsequent vocoder processing.
      The implications of preserving either the main harmonic components occurring at
      multiples of F0 or the main harmonics along with adjacent partials are
      investigated. This is done by first pre-processing noisy speech with a
      conventional noise-reduction algorithm, regenerating the harmonics, and vocoder
      processing the stimuli with eight channels of stimulation in steady speech-shaped
      noise. Results indicated that preserving the main low-frequency harmonics
      (spanning 1 or 3 kHz) alone was not beneficial. Preserving, however, the harmonic
      structure of the stimulus, i.e., the main harmonics along with the adjacent
      partials, was found to be critically important and provided substantial
      improvements (41 percentage points) in intelligibility.

PMID- 20058989
TI  - Unsteady laryngeal airflow simulations of the intra-glottal vortical structures.
AB  - The intra-glottal vortical structures developed in a static divergent glottis
      with continuous flow entering the glottis are characterized. Laryngeal airflow
      calculations are performed using the Large Eddy Simulation approach. It has been
      shown that intra-glottal vortices are formed on the divergent wall of the
      glottis, immediately downstream of the separation point. Even with non-pulsatile
      flow entering the glottis, the vortices are intermittently shed, producing
      unsteady flow at the glottal exit. The vortical structures are characterized by
      significant negative static pressure relative to the ambient pressure. These
      vortices increase in size and strength as they are convected downstream by the
      flow due to the entrained air from the supra-glottal region. The negative static
      pressures associated with the intra-glottal vortical structures suggest that the
      closing phase during phonation may be accelerated by such vortices. The intra
      glottal negative pressures can affect both vocal fold vibration and voice
      production.

PMID- 20058990
TI  - Acoustic consequences of articulatory variability during productions of /t/ and
      /k/ and its implications for speech error research.
AB  - An increasing number of studies has linked certain types of articulatory or
      acoustic variability with speech errors, but no study has yet examined the
      relationship between such articulatory variability and acoustics. The present
      study aims to evaluate the acoustic properties of articulatorily errorful /k/ and
      /t/ stimuli to determine whether these errors are consistently reflected in the
      acoustics. The most frequent error observed in the articulatory data is the
      production of /k/ and /t/ with simultaneous tongue tip and tongue dorsum
      constrictions. Spectral analysis of these stimuli's bursts shows that /k/ and /t/
      are differently affected by such co-production errors: co-production of tongue
      tip and tongue dorsum during intended /k/ results in typical /k/ spectra (and
      hence in tokens robustly classified as /k/), while co-productions during intended
      /t/ result in spectra with roughly equal prominence at both the mid-frequency
      (/k/-like) and high-frequency (/t/-like) ranges (and hence in tokens ambiguous
      between /k/ and /t/). This outcome is not due to an articulatory timing
      difference, but to tongue dorsum constriction having an overall greater effect on
      the acoustic than a tongue tip constriction when the two are co-produced.

PMID- 20058991
TI  - Catalan speakers' perception of word stress in unaccented contexts.
AB  - In unaccented contexts, formant frequency differences related to vowel reduction
      constitute a consistent cue to word stress in English, whereas in languages such
      as Spanish that have no systematic vowel reduction, stress perception is based on
      duration and intensity cues. This article examines the perception of word stress
      by speakers of Central Catalan, in which, due to its vowel reduction patterns,
      words either alternate stressed open vowels with unstressed mid-central vowels as
      in English or contain no vowel quality cues to stress, as in Spanish. Results
      show that Catalan listeners perceive stress based mainly on duration cues in both
      word types. Other cues pattern together with duration to make stress perception
      more robust. However, no single cue is absolutely necessary and trading effects
      compensate for a lack of differentiation in one dimension by changes in another
      dimension. In particular, speakers identify longer mid-central vowels as more
      stressed than shorter open vowels. These results and those obtained in other
      stress-accent languages provide cumulative evidence that word stress is perceived
      independently of pitch accents by relying on a set of cues with trading effects
      so that no single cue, including formant frequency differences related to vowel
      reduction, is absolutely necessary for stress perception.

PMID- 20058992
TI  - Spatial selective attention in a complex auditory environment such as polyphonic
      music.
AB  - To investigate the influence of spatial information in auditory scene analysis,
      polyphonic music (three parts in different timbres) was composed and presented in
      free field. Each part contained large falling interval jumps in the melody and
      the task of subjects was to detect these events in one part ("target part") while
      ignoring the other parts. All parts were either presented from the same location
      (0 degrees; overlap condition) or from different locations (-28 degrees, 0
      degrees, and 28 degrees or -56 degrees, 0 degrees, and 56 degrees in the
      azimuthal plane), with the target part being presented either at 0 degrees or at
      one of the right-sided locations. Results showed that spatial separation of 28
      degrees was sufficient for a significant improvement in target detection (i.e.,
      in the detection of large interval jumps) compared to the overlap condition,
      irrespective of the position (frontal or right) of the target part. A larger
      spatial separation of the parts resulted in further improvements only if the
      target part was lateralized. These data support the notion of improvement in the
      suppression of interfering signals with spatial sound source separation.
      Additionally, the data show that the position of the relevant sound source
      influences auditory performance.

PMID- 20058993
TI  - Perception of musical pitch and lexical tones by Mandarin-speaking musicians.
AB  - The relationship between music and language processing was explored in two
      perception experiments on the identification of musical notes and Mandarin tones.
      In the music task, Mandarin-speaking musicians were asked to identify musical
      notes of three timbres without a reference pitch. 72% of the musicians met the
      criterion for absolute pitch when an exact match was required, and 82% met the
      criterion when one-semitone errors were allowed. Accuracy of identification was
      negatively correlated with age of onset of musical training, and piano notes were
      identified more accurately than viola and pure tone stimuli. In the Mandarin
      task, the musicians were able to identify, beyond chance, brief Mandarin tone
      stimuli that were devoid of dynamic F0 information and cues commonly considered
      necessary for speaker normalization. Although F0 height detection was involved in
      both musical note and Mandarin tone identification, performances in the two tasks
      were not correlated. The putative link between absolute pitch and tone language
      experience was discussed.

PMID- 20058994
TI  - Major and minor music compared to excited and subdued speech.
AB  - The affective impact of music arises from a variety of factors, including
      intensity, tempo, rhythm, and tonal relationships. The emotional coloring evoked
      by intensity, tempo, and rhythm appears to arise from association with the
      characteristics of human behavior in the corresponding condition; however, how
      and why particular tonal relationships in music convey distinct emotional effects
      are not clear. The hypothesis examined here is that major and minor tone
      collections elicit different affective reactions because their spectra are
      similar to the spectra of voiced speech uttered in different emotional states. To
      evaluate this possibility the spectra of the intervals that distinguish major and
      minor music were compared to the spectra of voiced segments in excited and
      subdued speech using fundamental frequency and frequency ratios as measures.
      Consistent with the hypothesis, the spectra of major intervals are more similar
      to spectra found in excited speech, whereas the spectra of particular minor
      intervals are more similar to the spectra of subdued speech. These results
      suggest that the characteristic affective impact of major and minor tone
      collections arises from associations routinely made between particular musical
      intervals and voiced speech.

PMID- 20058995
TI  - An acoustical study of vocal pitch matching in congenital amusia.
AB  - Vocal pitch matching is a foundational skill for singing and is an interesting
      place to study the relationship between pitch perception and production. To
      better understand this relationship, we assessed pitch-matching abilities in
      congenital amusics, who have documented disabilities in pitch perception, and in
      matched controls under normal, masked, and guided feedback conditions. Their
      vocal productions were analyzed for fundamental frequency and showed that amusics
      were significantly less accurate at pitch matching than the controls. However,
      five of the six amusics showed a significant correlation between their produced
      pitches and the target pitch. Feedback condition had no effect on pitch-matching
      accuracy. These results show impaired vocal pitch-matching abilities in amusics
      but also show a relationship between perceived and produced pitches.

PMID- 20058996
TI  - Perceptual studies of violin body damping and vibrato.
AB  - This work explored how the perception of violin notes is influenced by the
      magnitude of the applied vibrato and by the level of damping of the violin
      resonance modes. Damping influences the "peakiness" of the frequency response,
      and vibrato interacts with this peakiness by producing fluctuations in spectral
      content as well as in frequency and amplitude. Initially, it was shown that
      thresholds for detecting a change in vibrato amplitude were independent of body
      damping, and thresholds for detecting a change in body damping were independent
      of vibrato amplitude. A study of perceptual similarity using triadic comparison
      showed that vibrato amplitude and damping were largely perceived as independent
      dimensions. A series of listening tests was conducted employing synthesized,
      recorded, or live performance to probe perceptual responses in terms of
      "liveliness" and preference. The results do not support the conclusion that
      liveliness results from the combination of the use of vibrato and a "peaky"
      violin response. Judgments based on listening to single notes showed inconsistent
      patterns for liveliness, while preferences were highest for damping that was
      slightly less than for a reference (real) violin. In contrast, judgments by
      players based on many notes showed preference for damping close to the reference
      value.

PMID- 20058997
TI  - Normal modes of a musical drumhead under non-uniform tension.
AB  - The effect of non-uniform tension on the normal modes of musical drumheads is
      examined. Using the standard (m,n) designation for the number of nodal diameters
      and circles, ideal circular membrane modes with m>0 are doubly degenerate. These
      degeneracies can be lifted by perturbations to the circular symmetry. Of
      practical interest to drummers are perturbations caused by non-uniform tension
      applied at the rim of the drum, leading in some cases to audible frequency
      splitting. The role of the (1,1) mode in practical drum tuning is analyzed using
      data obtained using time-averaged electronic speckle-pattern interferometry along
      with finite element analysis. The resulting model is then generalized to include
      all modes, using symmetry arguments along with a selection rule taken from group
      theory. The model compares favorably with both perturbation theory and finite
      element analysis, and is consistent with experimental observations.

PMID- 20058998
TI  - Detecting overblown flute fingerings from the residual noise spectrum.
AB  - Producing a tone by increasing the blowing pressure to excite a higher frequency
      impedance minimum, or overblowing, is widely used in standard flute technique. In
      this paper, the effect of overblowing a fingering is explored with spectral
      analysis, and a fingering detector is designed based on acoustical knowledge and
      pattern classification techniques. The detector performs signal analysis of the
      strong broadband signal, that is, spectrally shaped by the pipe impedance, and
      measures the spectral energy during the attack around multiples of the
      fundamental frequency sub-multiples over the first octave and a half. It is
      trained and evaluated on sounds recorded with four expert performers. They played
      six series of tones from overblown and regular fingerings, with frequencies that
      are octave- and non-octave-related to the playing frequency. The best of the four
      proposed sound descriptors allows for a detection error below 1.3% for notes with
      two and three fingerings (C(5), D(5), C(6), and Cmusical sharp(6)) and below 14%
      for four (E(6)) or five fingerings (G(6)). The error is shown to dramatically
      increase when two fingerings' impedance become too similar (E(6) and A(4) and
      G(6) and C(5)).

PMID- 20058999
TI  - A unifying fractional wave equation for compressional and shear waves.
AB  - This study has been motivated by the observed difference in the range of the
      power-law attenuation exponent for compressional and shear waves. Usually
      compressional attenuation increases with frequency to a power between 1 and 2,
      while shear wave attenuation often is described with powers less than 1. Another
      motivation is the apparent lack of partial differential equations with desirable
      properties such as causality that describe such wave propagation. Starting with a
      constitutive equation which is a generalized Hooke's law with a loss term
      containing a fractional derivative, one can derive a causal fractional wave
      equation previously given by Caputo [Geophys J. R. Astron. Soc. 13, 529-539
      (1967)] and Wismer [J. Acoust. Soc. Am. 120, 3493-3502 (2006)]. In the low
      omegatau (low-frequency) case, this equation has an attenuation with a power-law
      in the range from 1 to 2. This is consistent with, e.g., attenuation in tissue.
      In the often neglected high omegatau (high-frequency) case, it describes
      attenuation with a power-law between 0 and 1, consistent with what is observed
      in, e.g., dynamic elastography. Thus a unifying wave equation derived properly
      from constitutive equations can describe both cases.

PMID- 20059000
TI  - Thermal effects generated by high-intensity focused ultrasound beams at normal
      incidence to a bone surface.
AB  - Experiments and computations were performed to study factors affecting thermal
      safety when high-intensity focused ultrasound (HIFU) beams are normally incident
      (i.e., beam axis normal to the interface) upon a bone/soft-tissue interface. In
      particular, the temperature rise and thermal dose were determined as a function
      of separation between the beam focus and the interface. Under conditions
      representative of clinical HIFU procedures, it was found that the thermal dose at
      the bone surface can exceed the threshold for necrosis even when the beam focus
      is more than 4 cm from the bone. Experiments showed that reflection of the HIFU
      beam from the bone back into the transducer introduced temperature fluctuations
      of as much as +/-15% and may be an important consideration for safety analyses at
      sufficiently high acoustic power. The applicability of linear propagation models
      in predicting thermal dose near the interface was also addressed. Linear models,
      while underpredicting thermal dose at the focus, provided a conservative (slight
      overprediction) estimate of thermal dose at the bone surface. Finally,
      temperature rise due to absorption of shear waves generated by the HIFU beam in
      the bone was computed. Modeling shear-wave propagation in the thermal analysis
      showed that the predicted temperature rise off axis was as much as 30% higher
      when absorption of shear waves is included, indicating that enhanced heating due
      to shear-wave absorption is potentially important, even for normally incident
      HIFU beams.

PMID- 20059001
TI  - Propagation of narrow-band-high-frequency clicks: measured and modeled
      transmission loss of porpoise-like clicks in porpoise habitats.
AB  - Estimating the range at which harbor porpoises can detect prey items and
      environmental objects is integral to understanding their biosonar. Understanding
      the ranges at which they can use echolocation to detect and avoid obstacles is
      particularly important for strategies to reduce bycatch. Transmission loss (TL)
      during acoustic propagation is an important determinant of those detection
      ranges, and it also influences animal detection functions used in passive
      acoustic monitoring. However, common assumptions regarding TL have rarely been
      tested. Here, TL of synthetic porpoise clicks was measured in porpoise habitats
      in Canada and Denmark, and field data were compared with spherical spreading law
      and ray-trace (Bellhop) model predictions. Both models matched mean observations
      quite well in most cases, indicating that a spherical spreading law can usually
      provide an accurate first-order estimate of TL for porpoise sounds in porpoise
      habitat. However, TL varied significantly (+/-10 dB) between sites and over time
      in response to variability in seafloor characteristics, sound-speed profiles, and
      other short-timescale environmental fluctuations. Such variability should be
      taken into account in estimates of the ranges at which porpoises can communicate
      acoustically, detect echolocation targets, and be detected via passive acoustic
      monitoring.

PMID- 20059002
TI  - Depth dependent variation of the echolocation pulse rate of bottlenose dolphins
      (Tursiops truncatus).
AB  - Trained odontocetes appear to have good control over the timing (pulse rate) of
      their echolocation clicks; however, there is comparatively little information
      about how free-ranging odontocetes modify their echolocation in relation to their
      environment. This study investigates echolocation pulse rate in 14 groups of free
      ranging bottlenose dolphins (Tursiops truncatus) at a variety of depths (2.4-30.1
      m) in the Gulf of Mexico. Linear regression models indicated a significant
      decrease in mean pulse rate with mean water depth. Pulse rates for most groups
      were multi-modal. Distance to target estimates were as high as 91.8 m, assuming
      that echolocation was produced at a maximal rate for the target distance. A 5.29
      ms processing lag time was necessary to explain the pulse rate modes observed.
      Although echolocation is likely reverberation limited, these results support the
      hypotheses that free-ranging bottlenose dolphins in this area are adapting their
      echolocation signals for a variety of target detection and ranging purposes, and
      that the target distance is a function of water depth.

PMID- 20059003
TI  - Utilizing dual frequency band transmit pulse complexes in medical ultrasound
      imaging.
AB  - A method of acoustic imaging that potentially can improve the diagnostic
      capabilities of medical ultrasound is presented. The method, given the name SURF
      (Second order UltRasound Field) imaging, is achieved by processing the received
      signals from transmitted dual frequency band pulse complexes with at least partly
      overlapping high frequency (HF) and low frequency (LF) pulses. The transmitted HF
      pulses are used for image reconstruction, whereas the transmitted LF pulses are
      used to manipulate the elastic properties of the medium observed by the HF
      imaging pulses. The present paper discusses fundamental concepts in relation to
      the use of dual frequency band pulse complexes for medical ultrasound imaging.

PMID- 20059043
TI  - Correlation energy of two electrons in the high-density limit.
AB  - We consider the high-density-limit correlation energy E(c) in D > or = 2
      dimensions for the (1)S ground states of three two-electron systems: helium (in
      which the electrons move in a Coulombic field), spherium (in which they move on
      the surface of a sphere), and hookium (in which they move in a quadratic
      potential). We find that the E(c) values are strikingly similar, depending
      strongly on D but only weakly on the external potential. We conjecture that for
      large D, the limiting correlation energy E(c) approximately -delta(2)/8 in any
      confining external potential, where delta = 1/(D-1).

PMID- 20059044
TI  - Europium dimer: van der Waals molecule with extremely weak antiferromagnetic spin
      coupling.
AB  - High-level ab initio calculations reveal that the Eu(2) dimer is a van der Waals
      molecule with extremely weak antiferromagnetic spin coupling. The Heisenberg spin
      exchange model, validated by the multireference configuration interaction method,
      is used to construct the full set of model interaction potentials for the states
      with the total spin S ranging from 0 to 7 at the coupled cluster level of theory.
      This model establishes the singlet (1) summation operator(+) (g) state as the
      ground one of the dimer with the binding energy of 710 cm(-1), the vibrational
      frequency of 23 cm(-1) and the effective spin-coupling constant J estimated
      approximately -0.3 cm(-1).

PMID- 20059045
TI  - Large enhancement of the vibration-rotation coupling of the nu1 and nu3 states of
      silane in helium droplets.
AB  - Silane molecules have been embedded in helium droplets and studied via infrared
      laser depletion spectroscopy in the range of 2190 cm(-1). We found that the R1
      and Q2 lines of the nu(3) band have satellites shifted by about 2.3 cm(-1)
      towards low frequency and having similar intensity to the main lines. We assigned
      this perturbation in the spectrum to the coupling of the J=2 levels in nu(3) and
      close lying nu(1) vibration states. The strength of the coupling is a factor of
      about 50 larger in He droplets than in free molecules and have the same selection
      rules implied by the tetrahedral symmetry of SiH(4) molecules. The perturbation,
      which cannot be explained within the framework of a Hamiltonian of free
      molecules, is evidence of strong coupling of the molecule with some He
      excitations in the molecular vicinity.

PMID- 20059046
TI  - Thermally driven molecular linear motors: a molecular dynamics study.
AB  - We conduct molecular dynamics simulations of a molecular linear motor consisting
      of coaxial carbon nanotubes with a long outer carbon nanotube confining and
      guiding the motion of an inner short, capsulelike nanotube. The simulations
      indicate that the motion of the capsule can be controlled by thermophoretic
      forces induced by thermal gradients. The simulations find large terminal
      velocities of 100-400 nm/ns for imposed thermal gradients in the range of 1-3
      K/nm. Moreover, the results indicate that the thermophoretic force is velocity
      dependent and its magnitude decreases for increasing velocity.

PMID- 20059047
TI  - Merging bond-order potentials with charge equilibration.
AB  - A method is presented for extending any bond-order potential (BOP) to include
      charge transfer between atoms through a modification of the split-charge
      equilibration (SQE) formalism. Variable limits on the maximum allowed charge
      transfer between atomic pairs are defined by mapping bond order to an amount of
      shared charge in each bond. Charge transfer is interpreted as an asymmetry in how
      the shared charge is distributed between the atoms of the bond. Charge
      equilibration (QE) assesses the asymmetry of the shared charge, while the BOP
      converts this asymmetry to the actual amount of charge transferred. When applied
      to large molecules, this BOP/SQE method does not exhibit the unrealistic growth
      of charges that is often associated with QE models.

PMID- 20059048
TI  - Derivation of dynamical density functional theory using the projection operator
      technique.
AB  - Density functional theory is a particular case of a general theory of conjugate
      variables that serves as the basis of the projection operator technique. By using
      this technique we derive a general dynamical version of density functional theory
      which involves a generalized diffusion tensor. The diffusion tensor is given by a
      Green-Kubo expression. For Brownian dynamics of dilute colloidal suspensions, the
      standard dynamical density functional theory is recovered.

PMID- 20059049
TI  - An error-controlled fast multipole method.
AB  - We present a two-stage error estimation scheme for the fast multipole method
      (FMM). This scheme can be applied to any particle system. It incorporates
      homogeneous as well as inhomogeneous distributions. The FMM error as a
      consequence of the finite representation of the multipole expansions and the
      operator error is correlated with an absolute or relative user-requested energy
      threshold. Such a reliable error control is the basis for making reliable
      simulations in computational physics. Our FMM program on the basis of the two
      stage error estimation scheme is available on request.

PMID- 20059050
TI  - Competing nucleation pathways in a mixture of oppositely charged colloids: out-of
      equilibrium nucleation revisited.
AB  - Recent simulations of crystal nucleation from a compressed liquid of oppositely
      charged colloids show that the natural Brownian dynamics results in nuclei of a
      charge-disordered FCC (DFCC) solid whereas artificially accelerated dynamics with
      charge swap moves result in charge-ordered nuclei of a CsCl phase. These results
      were interpreted as a breakdown of the quasiequilibrium assumption for
      precritical nuclei. We use structure-specific nucleus size coordinates for the
      CsCl and DFCC structures and equilibrium based sampling methods to understand the
      dynamical effects on structure selectivity in this system. Nonequilibrium effects
      observed in previous simulations emerge from a diffusion tensor that dramatically
      changes when charge swap moves are used. Without the charge swap moves diffusion
      is strongly anisotropic with very slow motion along the charge-ordered CsCl axis
      and faster motion along the DFCC axis. Kramers-Langer-Berezhkovskii-Szabo theory
      predicts that under the realistic dynamics, the diffusion anisotropy shifts the
      current toward the DFCC axis. The diffusion tensor also varies with location on
      the free energy landscape. A numerical calculation of the current field with a
      diffusion tensor that depends on the location in the free energy landscape
      exacerbates the extent to which the current is skewed toward DFCC structures. Our
      analysis confirms that quasiequilibrium theories based on equilibrium properties
      can explain the nonequilibrium behavior of this system. Our analysis also shows
      that using a structure-specific nucleus size coordinate for each possible
      nucleation product can provide mechanistic insight on selectivity and competition
      between nucleation pathways.

PMID- 20059051
TI  - Close packing density of polydisperse hard spheres.
AB  - The most efficient way to pack equally sized spheres isotropically in three
      dimensions is known as the random close packed state, which provides a starting
      point for many approximations in physics and engineering. However, the particle
      size distribution of a real granular material is never monodisperse. Here we
      present a simple but accurate approximation for the random close packing density
      of hard spheres of any size distribution based upon a mapping onto a one
      dimensional problem. To test this theory we performed extensive simulations for
      mixtures of elastic spheres with hydrodynamic friction. The simulations show a
      general (but weak) dependence of the final (essentially hard sphere) packing
      density on fluid viscosity and on particle size but this can be eliminated by
      choosing a specific relation between mass and particle size, making the random
      close packed volume fraction well defined. Our theory agrees well with the
      simulations for bidisperse, tridisperse, and log-normal distributions and
      correctly reproduces the exact limits for large size ratios.

PMID- 20059052
TI  - A theoretical study of the low-lying excited states of thieno[3,4-b]pyrazine.
AB  - The low-lying electronic excited states of thieno[3,4-b]pyrazine have been
      studied using the multiconfigurational second-order perturbation CASPT2 theory
      with extended atomic natural orbital basis sets. The CASPT2 results allow for a
      full interpretation of the electronic absorption and emission spectra and provide
      valuable information for the rationalization of the experimental data. The
      nature, position, and intensity of the spectral bands have been analyzed in
      detail. A preliminary comparative study of the ground-state geometry of
      thieno[3,4-b]pyrazine has been performed at the coupled cluster single and
      doubles and density functional theory levels using a variety of correlation
      consistent basis sets. Thieno[3,4-b]pyrazine exhibits a polyene-like structure in
      the ground state due to the bond localization in the pyrazine moiety. An
      aromatization of the pyrazine unit is predicted for the lowest-energy electronic
      excited states.

PMID- 20059053
TI  - Higher-order symplectic integration in Born-Oppenheimer molecular dynamics.
AB  - The extended Lagrangian formulation of time-reversible Born-Oppenheimer molecular
      dynamics [A. M. N. Niklasson, C. J. Tymczak, and M. Challacombe, Phys. Rev. Lett.
      100, 123004 (2008); Phys. Rev. Lett. 97, 123001 (2006)] enables the use of
      geometric integrators in the propagation of both the nuclear and the electronic
      degrees of freedom on the Born-Oppenheimer potential energy surface. Different
      symplectic integrators up to the sixth order have been adapted and optimized in
      the framework of ab initio self-consistent-field theory. It is shown how the
      accuracy can be significantly improved compared to a conventional Verlet
      integration at the same level of computational cost, in particular, for the case
      of very high accuracy requirements.

PMID- 20059054
TI  - Coupling atomistic and continuum hydrodynamics through a mesoscopic model:
      application to liquid water.
AB  - We have conducted a triple-scale simulation of liquid water by concurrently
      coupling atomistic, mesoscopic, and continuum models of the liquid. The presented
      triple-scale hydrodynamic solver for molecular liquids enables the insertion of
      large molecules into the atomistic domain through a mesoscopic region. We show
      that the triple-scale scheme is robust against the details of the mesoscopic
      model owing to the conservation of linear momentum by the adaptive resolution
      forces. Our multiscale approach is designed for molecular simulations of open
      domains with relatively large molecules, either in the grand canonical ensemble
      or under nonequilibrium conditions.

PMID- 20059055
TI  - Accurate thermodynamics for short-ranged truncations of Coulomb interactions in
      site-site molecular models.
AB  - Coulomb interactions are present in a wide variety of all-atom force fields.
      Spherical truncations of these interactions permit fast simulations but are
      problematic due to their incorrect thermodynamics. Herein we demonstrate that
      simple analytical corrections for the thermodynamics of uniform truncated systems
      are possible. In particular, results for the simple point charge/extended (SPC/E)
      water model treated with spherically truncated Coulomb interactions suggested by
      local molecular field theory [J. M. Rodgers and J. D. Weeks, Proc. Natl. Acad.
      Sci. U.S.A. 105, 19136 (2008)] are presented. We extend the results developed by
      Chandler [J. Chem. Phys. 65, 2925 (1976)] so that we may treat the thermodynamics
      of mixtures of flexible charged and uncharged molecules simulated with spherical
      truncations. We show that the energy and pressure of spherically truncated bulk
      SPC/E water are easily corrected using exact second-moment-like conditions on
      long-ranged structure. Furthermore, applying the pressure correction as an
      external pressure removes the density errors observed by other research groups in
      NPT simulations of spherically truncated bulk species.

PMID- 20059056
TI  - Role of ionization in orientation dependence of molecular high-order harmonic
      generation.
AB  - We investigate the orientation dependence of high-order harmonic generation (HHG)
      from O(2) and CO(2) molecules using the strong-field approximation (SFA). Our
      simulations reveal the important modulation of the ionization to the HHG
      orientation dependence, especially at larger orientation angles. By virtue of a
      simplified model arising from the SFA, we show that this modulation can be read
      from the harmonic order where the HHG spectra at different orientation angles
      intersect. These results give suggestions on probing the molecular structure and
      dynamics using HHG.

PMID- 20059057
TI  - Conduction in graphenes.
AB  - It is shown that, within the tight-binding approximation, Fermi-level ballistic
      conduction for a perimeter-connected graphene fragment follows a simple selection
      rule: the zero eigenvalues of the molecular graph and of its subgraph minus both
      contact vertices must be equal in number, as must those of the two subgraphs with
      single contact vertices deleted. In chemical terms, the new rule therefore
      involves counting nonbonding orbitals of four molecules. The rule is initially
      derived within the source and sink potential scattering framework, but has
      equivalent forms that unify the molecular-orbital and valence-bond approaches to
      conduction. It is shown that the new selection rule can be cast in terms of
      Kekule counts, bond orders, and frontier-orbital coefficients. In particular, for
      a Kekulean graphene, conduction pathways are shown to be ranked in efficiency by
      a (nonmonotonic) function of Pauling bond order between the contact vertices.
      Frontier-orbital analysis of conduction approximates this function. For a
      monoradical graphene, the analogous function is shown to depend on Pauling spin
      densities at contact vertices.

PMID- 20059058
TI  - Critical points bifurcation analysis of high-l bending dynamics in acetylene.
AB  - The bending dynamics of acetylene with pure vibrational angular momentum
      excitation and quantum number l not = 0 are analyzed through the method of
      critical points analysis, used previously [V. Tyng and M. E. Kellman, J. Phys.
      Chem. B 110, 18859 (2006)] for l = 0 to find new anharmonic modes born in
      bifurcations of the low-energy normal modes. Critical points in the reduced phase
      space are computed for continuously varied bend polyad number N(b) = n(4) + n(5)
      as l = l(4) + l(5) is varied between 0 and 20. It is found that the local L,
      orthogonal O, precessional P, and counter-rotator CR families persist for all l.
      In addition, for l > or = 8, there is a fifth family of critical points which,
      unlike the previous families, has no fixed relative phase ("off great circle"
      OGC). The concept of the minimum energy path in the polyad space is developed.
      With restriction to l=0 this is the local mode family L. This has an intuitive
      relation to the minimum energy path or reaction mode for acetylene-vinylidene
      isomerization. With l > or = 0 included as a polyad number, the l = 0 minimum
      energy path forms a troughlike channel in the minimum energy surface in the
      polyad space, which consists of a complex mosaic of L, O, and OGC critical
      points. There is a division of the complete set of critical points into layers,
      the minimum energy surface forming the lowest.

PMID- 20059059
TI  - Global phase diagrams for a compressible polymer-solvent system using the full
      Tompa model.
AB  - We present the global phase diagrams for a compressible polymer-solvent system at
      the mathematical double point and its environment by using the full Tompa model
      for varying numbers of segments in each polymer chain. A principal transition
      mechanism is a mathematical double point at which two critical lines meet and
      exchange branches. We present the critical lines in the density-density and the
      P, T planes in detail. The locations of all significant features of the phase
      diagrams are described and compared with Scott and van Konynenburg phase diagram
      classifications. We find the type II, type III or type IV phase diagram behaviors
      of the Scott and van Konynenburg classifications. It is also found that the
      critical lines and phase behavior are extremely sensitive to small modifications
      in the chain length parameter.

PMID- 20059060
TI  - Four-component relativistic theory for nuclear magnetic shielding: magnetically
      balanced gauge-including atomic orbitals.
AB  - It is recognized only recently that the incorporation of the magnetic balance
      condition is absolutely essential for four-component relativistic theories of
      magnetic properties. Another important issue to be handled is the so-called gauge
      problem in calculations of, e.g., molecular magnetic shielding tensors with
      finite bases. It is shown here that the magnetic balance can be adapted to
      distributed gauge origins, leading to, e.g., magnetically balanced gauge
      including atomic orbitals (MB-GIAOs) in which each magnetically balanced atomic
      orbital has its own local gauge origin placed on its center. Such a MB-GIAO
      scheme can be combined with any level of theory for electron correlation. The
      first implementation is done here at the coupled-perturbed Dirac-Kohn-Sham level.
      The calculated molecular magnetic shielding tensors are not only independent of
      the choice of gauge origin but also converge rapidly to the basis set limit.
      Close inspections reveal that (zeroth order) negative energy states are only
      important for the expansion of first order electronic core orbitals. Their
      contributions to the paramagnetism are therefore transferable from atoms to
      molecule and are essentially canceled out for chemical shifts. This allows for
      simplifications of the coupled-perturbed equations.

PMID- 20059061
TI  - Competition between current-induced excitation and bath-induced decoherence in
      molecular junctions.
AB  - A general framework is presented to describe a resonant inelastic current
      inducing dynamics in the nuclear degrees of freedom of a molecule embedded
      between two electrodes. This approach makes use of the scattering theory of
      density matrices to account for the interaction between the scattering charge and
      the molecular modes to all orders and reduces in appropriate limits to both the
      standard master equation treatment for vibrational heating and the Landauer
      formalism for purely elastic transport. While the method presented here is
      equivalent to these approaches in limiting cases, it also goes well beyond their
      restrictions by incorporating the full quantum dynamics in the vibrational
      subspace in the presence of tunneling current. By application to the Au-C(60)-Au
      junction, it is shown that inclusion of vibrational coherences, which were
      previously neglected, is crucial to accurately predict the dynamics induced by
      current in molecular devices. Interaction with a bath of phonon modes is
      incorporated within the Bloch model and the competition between the bath-induced
      relaxation processes and the current-induced excitation is studied in detail over
      a range of temperatures.

PMID- 20059062
TI  - Molecular modeling of intermolecular and intramolecular excluded volume
      interactions for polymers at interfaces.
AB  - A hybrid modeling approach is proposed for inhomogeneous polymer solutions. The
      method is illustrated for the depletion problem with polymer chains up to N=10(3)
      segments in semidilute solutions and good solvent conditions. In a three
      dimensional volume, a set of freely jointed chains is considered for which the
      translational degrees of freedom are sampled using a coarse grained Monte Carlo
      simulation and the conformational degrees of freedom of the chains are computed
      using a modified self-consistent field theory. As a result, both intramolecular
      and intermolecular excluded volume effects are accounted for, not only for chains
      near the surface, but in the bulk as well. Results are consistent with computer
      simulations and scaling considerations. More specifically, the depletion
      thickness, which is a measure for the bulk correlation length, scales as delta
      proportional to phi(-0.75) and converges to the mean field result in the
      concentrated regime.

PMID- 20059063
TI  - The subtleties of explicitly correlated Z-averaged perturbation theory: choosing
      an R12 method for high-spin open-shell molecules.
AB  - Explicitly correlated MP2-R12 and coupled cluster R12 methods have proven to be
      effective in achieving the basis set limit of correlated wave function methods.
      However, correlated methods for high-spin open-shell states are typically based
      on semicanonical orbitals, leading to an unrestricted formalism, which for double
      excitations requires three independent sets of amplitudes. In contrast, Z
      averaged perturbation theory redefines the Hamiltonian with a symmetric exchange
      operator, thereby allowing a spin-restricted formulation with equivalent alpha
      and beta subspaces. In the current work, we present a preliminary study of
      explicitly correlated ZAPT for second-order perturbation theory. The superior
      basis set convergence of R12 methods is demonstrated for a set of atomization
      energies, showing the R12 results to be competitive with common basis set
      extrapolation techniques, albeit at a fraction of the cost. Given the efficiency
      gains associated with the symmetric exchange operator, we suggest ZAPT as a
      candidate for reducing the cost of current open-shell MP2-R12 and CCSD(T)-R12
      computations.

PMID- 20059064
TI  - Microscopic derivation of discrete hydrodynamics.
AB  - By using the standard theory of coarse graining based on Zwanzig's projection
      operator, we derive the dynamic equations for discrete hydrodynamic variables.
      These hydrodynamic variables are defined in terms of the Delaunay triangulation.
      The resulting microscopically derived equations can be understood, a posteriori,
      as a discretization on an arbitrary irregular grid of the Navier-Stokes
      equations. The microscopic derivation provides a set of discrete equations that
      exactly conserves mass, momentum, and energy and the dissipative part of the
      dynamics produces strict entropy increase. In addition, the microscopic
      derivation provides a practical implementation of thermal fluctuations in a way
      that the fluctuation-dissipation theorem is satisfied exactly. This paper points
      toward a close connection between coarse-graining procedures from microscopic
      dynamics and discretization schemes for partial differential equations.

PMID- 20059065
TI  - A density-functional approximation for relativistic kinetic energy.
AB  - A density-functional approximation for the relativistic kinetic energy of a many
      electron system is introduced, depending on the total particle density and the
      (nonrelativistic) kinetic energy density. The resulting scalar variational
      orbital equation is similar to Schrodinger's nonrelativistic equation, but
      includes relativistic mass-velocity effects to all orders in p. We test the
      theory by computing relativistic orbitals in the uranium atom and comparing their
      energies and mean radii with Dirac and zeroth-order regular approximation
      results.

PMID- 20059066
TI  - Prediction of charge-transfer excitations in coumarin-based dyes using a range
      separated functional tuned from first principles.
AB  - We study the description of charge-transfer excitations in a series of coumarin
      based donor-bridge-acceptor dyes. We show that excellent predictive power for the
      excitation energies and oscillator strengths in these systems is obtained by
      using a range-separated hybrid functional within the generalized Kohn-Sham
      approach to time-dependent density functional theory. Key to this success is a
      step for tuning the range separation parameter from first principles. We explore
      different methods for this tuning step, which are variants of a recently
      suggested approach for charge-transfer excitations [T. Stein et al., J. Am. Chem.
      Soc. 131, 2818 (2009)]. We assess the quality of prediction by comparing to
      excitation energies previously published for the same systems using the
      approximate coupled-cluster singles and doubles (CC2) method.

PMID- 20059067
TI  - Partial ion yield spectroscopy around the Cl 2p and C 1s ionization thresholds in
      CF3Cl.
AB  - We present a partial ion yield experiment on freon 13, CF(3)Cl, excited in the
      vicinity of the C 1s and Cl 2p ionization thresholds. We have collected a large
      amount of cationic fragments and a few anionic fragments at both edges. We have
      observed a strong intensity dependence of Rydberg transitions with ion fragment
      size for the CF(n)Cl(+) and CF(n)(+)/F(+) (n=0-3) series at both the Cl 2p and C
      1s ionization edges. Selectivity in the fragmentation processes involving the C
      Cl and C-F bonds are highlighted by the intensities of the C 1s to lowest
      unoccupied molecular orbital (LUMO) and LUMO+1 transitions measured on the
      CF(n)Cl(+) and CF(n)(+) yields. Equally, by comparison with their cation
      counterpart, we discuss possible bond-length dependence for the anion formation
      at the carbon 1s edge.

PMID- 20059068
TI  - Quasiclassical trajectory calculations of correlated product distributions for
      the F + CHD3(v1 = 0, 1) reactions using an ab initio potential energy surface.
AB  - We report quasiclassical trajectory (QCT) calculations of the correlated product
      distributions and branching ratios of the reactions F+CHD(3)(v(1)=0,1)-
      >HF(v)+CD(3)(v) and DF(v)+CHD(2)(v) using a recently published ab initio-based
      full-dimensional global potential energy surface [G. Czako et al., J. Chem. Phys.
      130, 084301 (2009)]. Harmonic normal mode analysis is done for the methyl
      products to determine the classical actions of each normal mode and then standard
      histogram binning and Gaussian binning (GB) methods are employed to obtain
      quantum state-resolved probabilities of the products. QCT calculations have been
      performed for both the vibrationally ground state and the CH stretching excited
      F+CHD(3)(v(1)=0,1) reactions at eight different collision energies in the 0.5-7.0
      kcal/mol range. HF and DF vibrationally state-resolved rotational and angular
      distributions, CD(3) and CHD(2) mode-specific vibrational distributions, and
      correlated vibrationally state-specific distributions for the product pairs have
      been obtained and the correlated results were compared to the experiment. We find
      that the use of GB can be advantageous especially in the threshold regions. The
      CH stretching excitation in the reactant does not change the CD(3) vibrational
      distributions significantly, whereas the HF molecules become vibrationally and
      rotationally hotter. On the other hand in the case of the DF+CHD(2) channel the
      initially excited CH stretch appears mainly "intact" in the CHD(2) product and
      the DF distributions are virtually the same as formed from the ground state
      CHD(3) reaction. The computed results qualitatively agree with recent crossed
      molecular beam experiment [W. Zhang et al., Science 325, 303 (2009)] that (a)
      CHD(2)(v(1)=1) is the most populated product state of the F+CHD(3)(v(1)=1)
      reaction and this reaction produces much less CHD(2)(v=0) compared to the
      reaction F+CHD(3)(v=0); (b) the cross section ratio of CHD(2)(v(1)=1):CHD(2)(v=0)
      formed from the reactions F+CHD(3)(v(1)=1):F+CHD(3)(v=0) is less than 1 and shows
      little collision energy dependency; (c) the reactant CH stretch excitation
      increases the DF:HF ratio at low collision energies; (d) the correlated
      vibrational and angular distributions for DF(v)+CHD(2)(v(1)=0,1) from the ground
      state and stretch-excited reactions, respectively, are almost identical.

PMID- 20059069
TI  - A five-dimensional quantum dynamics study of the F(2P) + CH4 reaction.
AB  - By applying the semirigid vibrating rotor target (SVRT) model to the title
      reaction, five-dimensional wave packet quantum dynamics calculations have been
      carried out on the new potential energy surface PES-2006 [Espinosa-Garcia et al.,
      J. Phys. Chem. A 111, 2761 (2007)]. The reaction probabilities have been
      calculated for total angular momentum J up to 105 to obtain the converged
      integral cross sections over a collision energy range of 0.01-0.345 eV. With the
      polyatomic system initially in its ground rovibrational state |000>, no obvious
      resonance signature has been observed in the integral cross sections although it
      appears in the reaction probabilities for J < or = 40. However, when the umbrella
      mode of the collision system is initially excited to nu(alpha0) = 1 level, |001>
      state, there is resonance signature in both the reaction probabilities with J <
      or = 55 and the integral cross sections. In addition, rate constants are
      calculated by Boltzmann averaging of the |000> integral cross sections over
      collision energy and compared with both the previous kinetic calculations and the
      experimental measurements. A reasonable agreement has been achieved over the
      investigated temperature range of 180-400 K.

PMID- 20059070
TI  - Theoretical characteristics of the bound states of M-X complexes (M = Cu, Ag, and
      Au, and X = He, Ne, and Ar).
AB  - The potential energy curves (PECs) of the bound states of M-X (M=Cu, Ag, and Au
      and X=He, Ne, and Ar) complexes have been calculated using the coupled cluster
      singles and doubles method with perturbative treatment of triple excitations.
      Large basis sets and bond functions, as well as the basis set superposition
      errors, are employed to obtain accurate PECs. The analytical potential energy
      functions (APEFs) are fitted using the PECs. The vibrational energy levels and
      the spectroscopic parameters for the complexes are determined using our APEFs and
      compared to the theoretical works available at present. We also find that the
      PECs are bound with similar van der Waals interactions, which implies that He,
      Ne, and Ar may be used for buffer-gas cooling; and Cu, Ag, and Au may be trapped
      with a similar method because Cu and Ag have been experimentally trapped with He
      buffer-gas cooling.

PMID- 20059071
TI  - Dynamics of proton migration and dissociation in core-excited ethyne probed by
      multiple ion momentum imaging.
AB  - The study focuses on the rapid geometry change in ethyne excited near the carbon
      1s edge. Core excitation and ionization lead to population of dicationic states
      in ethyne. We study three competing dissociation pathways associated with
      deprotonation in the linear ethyne molecule, and two cases of rapid proton
      migration. We investigate the alignment of the molecule in the excited state and
      find startling differences in these three cases. We present evidence for a strong
      anisotropy in the production of H(2)(+)/C(2)(+) fragments through a rapid
      deformation of the molecule to a dibridged conformation with the transition
      dipole moment parallel to the polarization of the exciting radiation.

PMID- 20059072
TI  - Adiabatic and diabatic invariants in ion-molecule reactions.
AB  - A point charge interacting with a dipole (either induced or permanent)
      constitutes a completely integrable dynamical subsystem characterized by three
      first integrals of the motion (E, p(phi), and either l(2) or a Hamilton-Jacobi
      separation constant beta). An ion-molecule reaction (capture or fragmentation)
      can be seen as an interaction between such a subsystem and a bath of oscillators.
      This interaction is a perturbation that destroys some of the first integrals.
      However, the perturbation depends on the separation between the fragments and the
      destruction is gradual. The mathematical simplicity of the long-range
      electrostatic interaction potential leads to useful simplifications. A first
      order perturbation treatment based on the structured and regular nature of the
      multipole expansion is presented. The separating integrals valid in the
      asymptotic limit are found to subsist at intermediate distances, although in a
      weaker form. As the reaction coordinate decreases, i.e., as the fragments
      approach, the asymptotic range is followed by an outer region where (i) the
      azimuthal momentum p(phi) remains a constant of the motion; (ii) the square
      angular momentum l(2) or the separation constant beta transform into a diabatic
      invariant in regions of phase space characterized by a high value of the
      translational momentum p(r); (iii) for low values of p(r), it is advantageous to
      use the action integral contour integral(p(theta)d theta), which is an adiabatic
      invariant. The conditions under which an effective potential obtained by adding
      centrifugal repulsion to an electrostatic attractive term can be validly
      constructed are specified. In short, the dynamics of ion-molecule interactions is
      still regular in parts of phase space corresponding to a range of the reaction
      coordinate where the interaction potential deviates from its asymptotic shape.

PMID- 20059073
TI  - The dynamics of highly excited electronic systems: applications of the electron
      force field.
AB  - Highly excited heterogeneous complex materials are essential elements of
      important processes, ranging from inertial confinement fusion to semiconductor
      device fabrication. Understanding the dynamics of these systems has been
      challenging because of the difficulty in extracting mechanistic information from
      either experiment or theory. We describe here the electron force field (eFF)
      approximation to quantum mechanics which provides a practical approach to
      simulating the dynamics of such systems. eFF includes all the normal
      electrostatic interactions between electrons and nuclei and the normal quantum
      mechanical description of kinetic energy for the electrons, but contains two
      severe approximations: first, the individual electrons are represented as
      floating Gaussian wave packets whose position and size respond instantaneously to
      various forces during the dynamics; and second, these wave packets are combined
      into a many-body wave function as a Hartree product without explicit
      antisymmetrization. The Pauli principle is accounted for by adding an extra spin
      dependent term to the Hamiltonian. These approximations are a logical extension
      of existing approaches to simulate the dynamics of fermions, which we review. In
      this paper, we discuss the details of the equations of motion and potentials that
      form eFF, and evaluate the ability of eFF to describe ground-state systems
      containing covalent, ionic, multicenter, and/or metallic bonds. We also summarize
      two eFF calculations previously reported on electronically excited systems: (1)
      the thermodynamics of hydrogen compressed up to ten times liquid density and
      heated up to 200,000 K; and (2) the dynamics of Auger fragmentation in a diamond
      nanoparticle, where hundreds of electron volts of excitation energy are
      dissipated over tens of femtoseconds. These cases represent the first steps
      toward using eFF to model highly excited electronic processes in complex
      materials.

PMID- 20059074
TI  - Recombination of polaron and exciton in conjugated polymers.
AB  - Both polarons and excitons, which are composite particles with internal lattice
      structure, play an important role in the transport and light-emitting properties
      of conjugated polymers for the use in, e.g., polymer based light-emitting diodes
      (LEDs). The scattering and recombination processes between a triplet exciton and
      a polaron are investigated using a nonadiabatic evolution method based on an
      extended Su-Schrieffer-Heeger model including interchain interactions. The
      results show that an excited polaron state can be formed, besides a triplet
      exciton is converted into a singlet exciton by the polaron. Moreover, the yields
      of both the singlet exciton and the excited polaron states increase with
      increasing interchain coupling strength. The excited polaron is luminescent due
      to radiative decay as is the singlet exciton. Therefore, our results indicate
      that the quantum efficiency of polymer LEDs could be enhanced by polaron-exciton
      recombination.

PMID- 20059075
TI  - An energy dispersive x-ray scattering and molecular dynamics study of liquid
      dimethyl carbonate.
AB  - In this work, we report on the first x-ray diffraction study on liquid dimethyl
      carbonate. Diffraction spectra were collected with an energy-dispersive
      instrument, whose wide Q-range allows the structure determination of weakly
      ordered systems (such as liquids). The structural correlation in this liquid
      ranges up to about 20 A. The observed patterns are interpreted with a structural
      model derived from classical molecular dynamics simulations. The simulations were
      run using OPLS force field, only slightly modified to restrain bond distances to
      the experimental values. The model structure function and radial distribution
      functions, averaged among the productive trajectory frames, are in very good
      agreement with the corresponding experimental ones. Molecular dynamics results
      show that the deviations from C(2v) cis-cis structure, predicted by ab initio
      calculations and observed by electron diffraction in the gas phase, are small. By
      analyzing the intra- and intermolecular pair distribution functions, it was
      possible to assign the peaks of the experimental radial distribution function to
      specific structural correlations, and to compute the different average
      intermolecular coordination numbers. The intermolecular methyl-carbonyl oxygen
      distance is thoroughly discussed to assess the presence of weak C-H...O hydrogen
      bonds.

PMID- 20059076
TI  - Theory of damped quantum rotation in nuclear magnetic resonance spectra. III.
      Nuclear permutation symmetry of the line shape equation.
AB  - The damped quantum rotation (DQR) theory describes manifestations in nuclear
      magnetic resonance spectra of the coherent and stochastic dynamics of N-fold
      molecular rotors composed of indistinguishable particles. The standard jump model
      is only a limiting case of the DQR approach; outside this limit, the stochastic
      motions of such rotors have no kinematic description. In this paper, completing
      the previous two of this series, consequences of nuclear permutation symmetry for
      the properties of the DQR line shape equation are considered. The systems
      addressed are planar rotors, such as aromatic hydrocarbons' rings, occurring
      inside of molecular crystals oriented in the magnetic field. Under such
      conditions, oddfold rotors can have nontrivial permutation symmetries only for
      peculiar orientations while evenfold ones always retain their intrinsic symmetry
      element, which is rotation by 180 degrees about the N-fold axis; in specific
      orientations the latter can gain two additional symmetry elements. It is shown
      that the symmetry selection rules applicable to the classical rate processes in
      fluids, once recognized as having two diverse aspects, macroscopic and
      microscopic, are also rigorously valid for the DQR processes in the solid state.
      However, formal justification of these rules is different because the DQR
      equation is based on the Pauli principle, which is ignored in the jump model. For
      objects like the benzene ring, exploitation of these rules in simulations of
      spectra using the DQR equation can be of critical significance for the
      feasibility of the calculations. Examples of such calculations for the proton
      system of the benzene ring in a general orientation are provided. It is also
      shown that, because of the intrinsic symmetries of the evenfold rotors, many of
      the DQR processes, which such rotors can undergo, are unobservable in NMR
      spectra.

PMID- 20059077
TI  - Oxidation states of graphene: insights from computational spectroscopy.
AB  - When it is oxidized, graphite can be easily exfoliated forming graphene oxide
      (GO). GO is a critical intermediate for massive production of graphene, and it is
      also an important material with various application potentials. With many
      different oxidation species randomly distributed on the basal plane, GO has a
      complicated nonstoichiometric atomic structure that is still not well understood
      in spite of intensive studies involving many experimental techniques.
      Controversies often exist in experimental data interpretation. We report here a
      first principles study on binding energy of carbon 1s orbital in GO. The
      calculated results can be well used to interpret experimental x-ray photoelectron
      spectroscopy (XPS) data and provide a unified spectral assignment. Based on the
      first principles understanding of XPS, a GO structure model containing new
      oxidation species epoxy pair and epoxy-hydroxy pair is proposed. Our results
      demonstrate that first principles computational spectroscopy provides a powerful
      means to investigate GO structure.

PMID- 20059078
TI  - Quantum Monte Carlo study of large spin-polarized tritium clusters.
AB  - This work expands recent investigations in the field of spin-polarized tritium (T
      downward arrow) clusters. We report the results for the ground-state energy and
      structural properties of large T downward arrow clusters consisting of up to 320
      atoms. All calculations have been performed with variational and diffusion Monte
      Carlo methods, using an accurate ab initio interatomic potential. Our results for
      N < or = 40 are in good agreement with results obtained by other groups. Using a
      liquid-drop expression for the energy per particle, we estimate the liquid
      equilibrium density, which is in good agreement with our recently obtained
      results for bulk T downward arrow. In addition, the calculations of the energy
      for large clusters have allowed for an estimation of the surface tension. From
      the mean-square radius of the drop, determined using unbiased estimators, we
      determine the dependence of the radii on the size of the cluster and extract the
      unit radius of the T downward arrow liquid.

PMID- 20059079
TI  - Polar solvation dynamics of coumarin 153 by ultrafast time-resolved fluorescence.
AB  - Polar solvation dynamics of coumarin 153 in acetonitrile, methanol, and butanol
      are investigated by dynamic Stokes shift function, S(t). In small protic
      solvents, it is known that an initial ultrafast component below 50 fs constitutes
      more than half of the total solvation process. We use fluorescence up-conversion
      technique via two-photon absorption process, which can provide 40 fs time
      resolution for the whole emission wavelength range. Moreover, time-resolved
      fluorescence spectra are recorded directly without the spectral reconstruction.
      We observe a temporal oscillation in frequency of whole emission spectrum in the
      solvation curve. In the obtained S(t), initial solvation time scale is 120 fs,
      invariant to solvents used in this experiment, although its amplitude varies in
      different solvents.

PMID- 20059080
TI  - Complete basis set limit second-order Moller-Plesset calculations for the fcc
      lattices of neon, argon, krypton, and xenon.
AB  - Complete basis set (CBS) limit calculations using second-order Moller-Plesset
      (MP2) theory for electron correlation within a many-body expansion of the
      interaction potential up to third order are carried out for the fcc lattices of
      Ne, Ar, Kr, and Xe. Lattice constants and cohesive energies from recent localized
      MP2 solid-state calculations by Halo et al. [Chem. Phys. Lett. 467, 294 (2009)]
      are in reasonable agreement with our CBS limit results. A detailed analysis
      reveals that MP2 severely underestimates long-range three-body effects, thus the
      Axilrod-Teller term is incorrectly described causing bond contractions for all
      rare gas solids considered. Further, any deviations in the MP2 lattice constant,
      cohesive energy, and bulk modulus can be traced back to inaccuracies in the
      binding energy and equilibrium distance of the rare gas dimer. Without inclusion
      of phonon dispersion, MP2 prefers the hcp over the fcc crystal structure for all
      rare gas solids considered.

PMID- 20059081
TI  - Comparative study of electroabsorption spectra of polar and nonpolar organic
      molecules in solution and in a polymer film.
AB  - Electroabsorption (EA) spectra of polar and nonpolar molecules of coumarin 153
      (C153) and pyrene in solution and in a polymer film of polymethylmethacrylate
      (PMMA) have been measured in the UV-visible region at room temperature. The shape
      of the EA spectra of C153 in benzene, 1,4-dioxane, or monochlorobenzene
      remarkably depends on the angle between the polarization direction of the
      absorption light and the applied electric field, whereas the EA spectra of C153
      doped in PMMA show only the Stark shift and the field-induced change in spectral
      shape is negligible. These results demonstrate that C153 is reoriented by
      application of electric fields in solution, but the molecules are immobilized in
      a PMMA film. Based on the EA spectra, electric dipole moments both in the ground
      state and in the excited state have been evaluated for C153 in different
      solvents. In the EA spectra of pyrene, only the Stark shift is observed both in
      solution and in PMMA, indicating that the field-induced molecular reorientation
      does not occur both in solution and in PMMA. The change in dipole moment of C153
      as well as the change in molecular polarizability of pyrene following absorption
      is much larger in solution than that in PMMA.

PMID- 20059082
TI  - Accurate description of phase diagram of clathrate hydrates at the molecular
      level.
AB  - In order to accurately estimate the thermodynamic properties of hydrogen
      clathrate hydrates, we developed a method based on the solid solution theory of
      van der Waals and Platteeuw. This model allows one to take into account the
      influence of guest molecules on the host lattice and guest-guest interactions-
      especially when more than one guest molecule occupies a cage. The free energies,
      equations of state, and chemical potentials of hydrogen and mixed propane
      hydrogen clathrate hydrates of cubic structure II with different cage fillings
      have been estimated using this approach. Moreover, the proposed theory has been
      used for construction p-T phase diagrams of hydrogen hydrate and mixed hydrogen
      propane hydrates in a wide range of pressures and temperatures. For the systems
      with well defined interactions the calculated curves of "guest gas-hydrate-ice
      I(h)" equilibrium agree with the available experimental data. We also believe
      that the present model allows one not only to calculate the hydrogen storage
      ability of known hydrogen hydrate but also predict this value for structures that
      have not yet been realized by experiment.

PMID- 20059083
TI  - Cluster sizes in direct and indirect molecular dynamics simulations of
      nucleation.
AB  - We performed molecular dynamics simulations of a Lennard-Jones fluid, and
      compared the sizes of critical clusters in direct simulations of a nucleation
      event in vapor phase with the sizes of clusters in stable equilibrium with the
      surrounding vapor. By applying different cluster criteria it is shown that both
      the critical clusters and the equilibrium clusters have dense cores of similar
      size but the critical clusters have more outlying cluster atoms surrounding this
      core. The cluster definition introduced by ten Wolde and Frenkel [J. Chem. Phys.
      109, 9901 (1998)], where each cluster atom must have at least five neighboring
      atoms within the distance of 1.5 times the Lennard-Jones length parameter, agrees
      well with the cluster size obtained from classical nucleation theory, and we find
      this agreement to be independent of temperature. The cluster size obtained from
      the observed nucleation rates by the first nucleation theorem is larger than the
      classical estimate and much smaller than the size given by the density profile of
      the equilibrium cluster.

PMID- 20059084
TI  - Theoretical analysis of anharmonic coupling and cascading Raman signals observed
      with femtosecond stimulated Raman spectroscopy.
AB  - We present a classical theoretical treatment of a two-dimensional Raman
      spectroscopy based on the initiation of vibrational coherence with an impulsive
      Raman pump and subsequent probing by two-pulse femtosecond stimulated Raman
      spectroscopy (FSRS). The classical model offers an intuitive picture of the
      molecular dynamics initiated by each laser pulse and the generation of the signal
      field traveling along the probe wave vector. Previous reports have assigned the
      observed FSRS signals to anharmonic coupling between the impulsively driven
      vibration and the higher-frequency vibration observed with FSRS. However, we show
      that the observed signals are not due to anharmonic coupling, which is shown to
      be a fifth-order coherent Raman process, but instead due to cascades of coherent
      Raman signals. Specifically, the observed vibrational sidebands are generated by
      parallel cascades in which a coherent anti-Stokes or Stokes Raman spectroscopy
      (i.e., CARS or CSRS) field generated by the coherent coupling of the impulsive
      pump and the Raman pump pulses participates in a third-order FSRS transition.
      Additional sequential cascades are discussed that will give rise to cascade
      artifacts at the fundamental FSRS frequencies. It is shown that the intended
      fifth-order FSRS signals, generated by an anharmonic coupling mechanism, will
      produce signals of approximately 10(-4) DeltaOD (change in the optical density).
      The cascading signals, however, will produce stimulated Raman signal of
      approximately 10(-2) DeltaOD, as has been observed experimentally. Experiments
      probing deuterochloroform find significant sidebands of the CCl(3) bend, which
      has an E type symmetry, shifted from the A(1) type C-D and C-Cl stretching modes,
      despite the fact that third-order anharmonic coupling between these modes is
      forbidden by symmetry. Experiments probing a 50:50 mixture of chloroform and d
      chloroform find equivalent intensity signals of low-frequency CDCl(3) modes as
      sidebands shifted from both the C-D stretch of CDCl(3) and the C-H stretch of
      CHCl(3). Such intermolecular sidebands are allowed in the cascade mechanism, but
      are expected to be extremely small in the fifth-order frequency modulation
      mechanism. Each of these observations indicates that the observed signals are due
      to cascading third-order Raman signals.

PMID- 20059085
TI  - Spatial and temporal heterogeneity in supercooled glycerol: evidence from wide
      field single molecule imaging.
AB  - We quantify spatial and temporal heterogeneity in supercooled glycerol at
      T=T(g)+14 K employing a widefield detection scheme and using rubrene as the probe
      molecule. We describe how microscopy configuration affects measured intensity,
      linear dichroism, and the resulting autocorrelation function. Rotational
      relaxation times tau(c) of 241 probe molecules are measured, and we find spatial
      heterogeneity over almost three orders of magnitude present at this temperature.
      An approach for detecting temporally heterogeneous molecules and quantifying
      exchange times is introduced. Of molecules that can be assessed, approximately
      15% display evidence of temporal heterogeneity-changes of tau(c) during the
      measurement-that are detected with the analysis technique employed. Exchanges
      between dynamically disparate environments occur rarely but in the proportion
      expected given the rarity of very slowly rotating molecules present.
      Heterogeneous molecules are characterized by persistence and exchange times.
      Median exchange and persistence times of the molecules identified as
      heterogeneous relative to glycerol's structural relaxation time tau(alpha) are
      found to be tau(ex)/tau(alpha)=202 and tau(pers)/tau(alpha)=405, respectively.
      These results are discussed in the context of values of exchange times that have
      been determined in other experiments.

PMID- 20059086
TI  - Ionic diffusion and the topological origin of fragility in silicate glasses.
AB  - Mass transport in liquids and glass is intimately connected to the structure and
      topology of the disordered network. To investigate this problem, we measure the
      ionic diffusivity and fragility of a series of iron-bearing alkali-alkaline earth
      silicate glasses, substituting different types of alkali and alkaline earth
      cations while keeping the same ratio of network modifiers. Diffusion is studied
      around the glass transition temperature (T(g)) under a reducing atmosphere,
      leading to a reduction of Fe(3+) to Fe(2+), and inward diffusion of the modifier
      cations. In the SiO(2)-CaO-Fe(2)O(3)-A(2)O (A=Na, K, Rb, or Cs) glass series, we
      find that the Ca(2+) ions diffuse faster than alkali ions and that the activation
      energy of the Ca(2+) diffusion decreases with alkali size, a trend that is
      coincident with a decrease in liquid fragility. We have established a simple
      model for accurately describing the correlation between the fragility index (m)
      and T(g) based on a topological consideration of the glass network. The model
      builds on a temperature-dependent constraint approach where the Vogel temperature
      serves as a rigidity percolation threshold. This follows from our derivation of
      the Vogel-Fulcher-Tammann equation of viscosity from the more accurate Mauro-Yue
      Ellison-Gupta-Allan equation. The established model provides an excellent
      prediction of the relationship between fragility and T(g), except for the MgO
      containing glass where Mg(2+) is known to play a unique topological role in the
      network. This trend is in coincidence with the considerably faster inward
      diffusion of Mg(2+) in comparison to other alkaline earth cations.

PMID- 20059087
TI  - Nucleation and growth of C60 nanoparticles from the supersaturated vapor and from
      the undercooled liquid: a molecular simulation study.
AB  - Using molecular simulation, we study the molecular mechanisms underlying the
      nucleation and growth of C(60) nanoparticles from the supersaturated vapor and
      from the undercooled liquid. We show that in both cases, nucleation proceeds
      through the formation of small clusters composed of the metastable hexagonal
      close-packed (HCP) polymorph. This observation differs from the nucleation
      pathway of simple systems (e.g., modeled by Lennard-Jones potential) in which the
      nucleation proceeds through the metastable body-centered cubic polymorph. We
      rationalize this observation in terms of the relative steepness of the repulsion
      for the different potential models. Finally, we observe two different types of
      growth leading either to crystallites dominated by the metastable HCP polymorph
      or to crystallites whose structure is predominantly that of the stable face
      centered cubic (FCC) polymorph. This finding is consistent with experiments on
      the crystallization of C(60) from the vapor, which reported the formation of FCC
      and HCP crystals.

PMID- 20059088
TI  - Theoretical study of one- and two-photon absorption spectra of azoaromatic
      compounds.
AB  - In this study, the one- and two-photon absorption spectra of seven azoaromatic
      compounds (five pseudostilbenes-type and two aminoazobenzenes) were theoretically
      investigated using the density functional theory combined with the response
      functions formalism. The equilibrium molecular structure of each compound was
      obtained at three different levels of theory: Hartree-Fock, density functional
      theory (DFT), and Moller-Plesset 2. The effect of solvent on the equilibrium
      structure and the electronic transitions of the compounds were investigated using
      the polarizable continuum model. For the one-photon absorption, the allowed pi-
      >pi(*) transition energy showed to be dependent on the molecular structures and
      the effect of solvent, while the n-->pi(*) and pi-->pi(*)(n) transition energies
      exhibited only a slight dependence. An inversion between the bands corresponding
      to the pi-->pi(*) and n-->pi(*) states due to the effect of solvent was observed
      for the pseudostilbene-type compounds. To characterize the allowed two-photon
      absorption transitions for azoaromatic compounds, the response functions
      formalism combined with DFT using the hybrid B3LYP and PBE0 functionals and the
      long-range corrected CAM-B3LYP functional was employed. The theoretical results
      support the previous findings based on the three-state model. The model takes
      into account the ground and two electronic excited states and has already been
      used to describe and interpret the two-photon absorption spectrum of azoaromatic
      compounds. The highest energy two-photon allowed transition for the
      pseudostilbene-type compounds shows to be more effectively affected
      (approximately 20%) by the torsion of the molecular structure than the lowest
      allowed transition (approximately 10%). In order to elucidate the effect of the
      solvent on the two-photon absorption spectra, the lowest allowed two-photon
      transition (dipolar transition) for each compound was analyzed using a two-state
      approximation and the polarizable continuum model. The results obtained reveal
      that the effect of solvent increases drastically the two-photon cross-section of
      the dipolar transition of the pseudostilbene-type compounds. In general, the
      features of both one- and two-photon absorption spectra of the azoaromatic
      compounds are well reproduced by the theoretical calculations.

PMID- 20059089
TI  - Anharmonic OH vibrations in Mg(OH)2 (brucite): two-dimensional calculations and
      crystal-induced blueshift.
AB  - A two-dimensional quantum-mechanical vibrational model has been used to calculate
      the anharmonic OH vibrational frequencies in the layered Mg(OH)(2) (brucite)
      crystal. The underlying potential energy surface was generated by density
      functional theory (DFT) calculations. The resulting OH frequencies are upshifted
      (blueshifted) by about +75 cm(-1) with respect to the gas-phase OH frequency
      (+120 cm(-1) in experiments; the discrepancy is mainly due to inadequacies in the
      DFT and pseudopotential models). The Raman-IR split is about 50 cm(-1), both in
      the calculations and in experiments. We find that the blueshift phenomenon in
      brucite can qualitatively be explained by a parabolalike "OH frequency versus
      electric field" correlation curve pertaining to an OH(-) ion exposed to an
      electric field. We also find that it is primarily the neighbors within the
      Mg(OH)(2) layer that induce the blueshift while the interlayer interaction gives
      a smaller (and redshifting) contribution.

PMID- 20059090
TI  - Zero point energy leakage in condensed phase dynamics: an assessment of quantum
      simulation methods for liquid water.
AB  - The approximate quantum mechanical ring polymer molecular dynamics (RPMD) and
      linearized semiclassical initial value representation (LSC-IVR) methods are
      compared and contrasted in a study of the dynamics of the flexible q-TIP4P/F
      water model at room temperature. For this water model, a RPMD simulation gives a
      diffusion coefficient that is only a few percent larger than the classical
      diffusion coefficient, whereas a LSC-IVR simulation gives a diffusion coefficient
      that is three times larger. We attribute this discrepancy to the unphysical
      leakage of initially quantized zero point energy (ZPE) from the intramolecular to
      the intermolecular modes of the liquid as the LSC-IVR simulation progresses. In
      spite of this problem, which is avoided by construction in RPMD, the LSC-IVR may
      still provide a useful approximation to certain short-time dynamical properties
      which are not so strongly affected by the ZPE leakage. We illustrate this with an
      application to the liquid water dipole absorption spectrum, for which the RPMD
      approximation breaks down at frequencies in the O-H stretching region owing to
      contamination from the internal modes of the ring polymer. The LSC-IVR does not
      suffer from this difficulty and it appears to provide quite a promising way to
      calculate condensed phase vibrational spectra.

PMID- 20059091
TI  - Comparison of interionic/intermolecular vibrational dynamics between ionic
      liquids and concentrated electrolyte solutions.
AB  - In this study, we have compared the interionic/intermolecular vibrational
      dynamics of ionic liquids (ILs) and concentrated electrolyte solutions measured
      by femtosecond optically heterodyne-detected Raman-induced Kerr effect
      spectroscopy. A typical anion in ILs, bis(trifluoromethanesulfonyl)amide
      ([NTf(2)](-)), has been chosen as the anion for the sample ILs and concentrated
      electrolyte solutions. ILs used in this study are 1-butyl-3-methylimidazolium, 1
      butylpyridinium, N-butyl-N,N,N-triethylammonium, and 1-butyl-1
      methylpyrrolidinium with [NTf(2)](-). Li[NTf(2)] solutions (approximately 3.3 M)
      of water, methanol, propylene carbonate, and poly(ethylene glycol) have been
      selected as control samples. Kerr transients of the ILs and electrolyte solutions
      show intra- and interionic/intermolecular vibrational dynamics followed by slow
      picosecond overdamped relaxation. Fourier transform Kerr spectra have shown a
      difference in the relative intensities of intraionic vibrational bands of
      [NTf(2)](-) (280-350 cm(-1)) between the ILs and electrolyte solutions. The
      origin of the difference is attributed to the change in the conformational
      equilibrium between cisoid and transoid forms of [NTf(2)](-), which is caused by
      a favorable stabilization of dipolar cisoid form due to Li(+) and dipolar solvent
      molecules in the electrolyte solutions. Low-frequency Kerr spectra (0-200 cm(-1))
      exhibit unique features with the variation of cation and solvent species. The
      aromatic ILs have a prominent high-frequency librational motion at about 100 cm(
      1) in contrast to the case for the nonaromatic ones. The common structure of the
      spectra observed at about 20 cm(-1) likely comes from an interionic motion of
      [NTf(2)](-). The nonaromatic ILs allow a fair comparison with the electrolyte
      solutions of propylene carbonate and poly(ethylene glycol) because of the
      structural similarities. The comparison based on the first moment of the
      interionic/intermolecular vibrational spectrum suggests the stronger
      interionic/intermolecular interaction in the concentrated electrolyte solutions
      than the ILs.

PMID- 20059092
TI  - Adaptive kinetic Monte Carlo simulation of methanol decomposition on Cu(100).
AB  - The adaptive kinetic Monte Carlo method was used to calculate the decomposition
      dynamics of a methanol molecule on Cu(100) at room temperature over a time scale
      of minutes. Mechanisms of reaction were found using minimum mode following saddle
      point searches based on forces and energies from density functional theory. Rates
      of reaction were calculated with harmonic transition state theory. The dynamics
      followed a pathway from CH(3)OH, CH(3)O, CH(2)O, HCO, and finally to CO. Our
      calculations confirm that methanol decomposition starts with breaking the O-H
      bond followed by breaking C-H bonds in the dehydrogenated intermediates until CO
      is produced. The bridge site on the Cu(100) surface is the active site for
      scissoring chemical bonds. Reaction intermediates are mobile on the surface which
      allows them to find this active reaction site. This study illustrates how the
      adaptive kinetic Monte Carlo method can model the dynamics of surface chemistry
      from first principles.

PMID- 20059093
TI  - Topological considerations on microporous adsorption processes in simple models
      for pillared interlayered clays.
AB  - The microporous structure of pillared interlayered clays is determined by their
      interlayer separation and the distribution of the pillars that separate their
      layers. The pillars provide stability to these quasi-two-dimensional high surface
      area materials. In this work we present a topological analysis of available and
      accessible volumes within various simple models of pillared interlayered clays.
      Each model is characterized by a distribution of pillars. Both fully ordered
      structures and disordered pillar distributions with either attractive or
      repulsive interpillar correlations are considered. Particular attention is paid
      to the problem of accessibility. In systems with similar degrees of porosity,
      even when cavities within each model might be able to host the same adsorbate
      molecules, their accessibility will strongly depend on the pillar distribution.
      The theoretical analysis presented in this work may facilitate the interpretation
      of experimental results, pointing out those quantities that are key to describe
      the texture of the porous material.

PMID- 20059094
TI  - Effect of La doping on CO adsorption at ceria surfaces.
AB  - In this paper we use density functional theory corrected for on-site Coulomb
      interactions (DFT+U) to study the adsorption of CO at La-doped ceria (111) and
      (110) surfaces. Doping of ceria with La is known to enhance oxidation of CO to
      CO(2) and this study investigates the atomic level details of this reaction. With
      La(3+) doping, an [La(3+)-O(-)] defect state with an oxygen hole is formed at
      both surfaces. The formation energy of an oxygen vacancy is reduced and vacancy
      formation results in the appearance of Ce(3+), instead of hole compensation. On
      the doped surfaces weak and strong adsorption of CO is found. In the former, the
      molecule remains intact. In the latter, the final adsorption species depends
      strongly on the surface and whether oxygen vacancies are present or not. On (111)
      a CO(2)-like species forms, while on the (110) surface, mono- or bidentate
      carbonates are present. La-doping of ceria surfaces shows enhanced reactivity
      over the undoped surfaces and we discuss the origin of the enhanced reactivity
      and the nature of the surface species upon CO adsorption.

PMID- 20059095
TI  - Diffusive growth of fullerenes and carbon nanotubes.
AB  - The video of a growing fullerene within a carbon nanotube, initiated by a
      tungsten catalyst, provides a dramatic realization of a complex nanoscale
      process. While there may be many detailed models which can account for this
      growth, we propose one of the simplest possible models which is consistent with
      the major observed features of the growth process. In particular, we assume that
      the fullerene is immersed in a carbon vapor environment, and that the growth
      occurs as a consequence of the diffusion of the carbon vapor into the fullerene.
      Moreover, we assume that the classical diffusion equation applies in the region
      exterior to the fullerene and that a standard Stefan condition applies at the
      moving fullerene surface. We assume that the gaseous medium through which the
      carbon atoms diffuse is represented through the value of the diffusion
      coefficient D appearing in the classical diffusion equation. We also assume that
      the influence of the catalyst is felt through the value of the constant alpha
      appearing in the Stefan condition. Based on these assumptions, we derive simple
      similarity solutions for both spherical and ellipsoidal fullerenes which are
      entirely consistent with the observations. A corresponding analysis is provided
      for the longitudinal growth of a carbon nanotube.

PMID- 20059096
TI  - Antiferromagnetic spin ordering in the dissociative adsorption of H2 on Si(001):
      density-functional calculations.
AB  - The dissociative adsorption of an H(2) molecule on the Si(001) surface, which has
      been experimentally identified in terms of dissociation on one side of two
      adjacent Si dimers, is investigated by spin polarized density-functional
      calculations within the generalized-gradient approximation. In contrast to the
      prevailing nonmagnetic configuration of charge ordering, we propose a new ground
      state where the two single dangling bonds (DBs) created by H(2) dissociation are
      antiferromagnetically coupled with each other. Such a spin ordering is found to
      be energetically favored over the previously proposed charge ordering. In the
      latter configuration, the buckling of the two DBs amounts to a height difference
      (Delta h) of 0.63 A, caused by a Jahn-Teller-like distortion, while in the former
      configuration, their buckling is almost suppressed to be Delta h=0.03 A as a
      consequence of spin polarization.

PMID- 20059097
TI  - Ab initio study of EMIM-BF4 crystal interaction with a Li (100) surface as a
      model for ionic liquid/Li interfaces in Li-ion batteries.
AB  - We examined the atomic and electronic structures of an interface between a 1
      ethyl-3-methyl imidazolium tetrafluoroborate (EMIM-BF(4)) ionic-liquid crystal
      and a Li(100) surface by periodic density-functional calculations, as a model for
      a room-temperature ionic-liquid (RTIL) electrolyte/Li interface at a Li-ion
      battery electrode. Results are compared with our previous theoretical study of
      the EMIM-BF(4) molecular adsorption on Li surfaces [H. Valencia et al., Phys.
      Rev. B 78, 205402 (2008)]. For the EMIM-BF(4) crystal structure, the present
      projector augmented wave scheme with the generalized gradient approximation can
      reproduce rather correct intramolecular structures as well as satisfactory short
      ranged intermolecular distances, while long-range intermolecular distances are
      overestimated due to the lack of correct description of long-range dispersive
      interactions. We constructed a coherent crystal/crystal interface model where
      four EMIM-BF(4) pairs are stacked on a p(4x3) Li (100) surface cell so as to
      simulate RTIL-layer deposition on a Li surface. We observed significant
      attraction of surface Li ions toward contacting BF(4)(-) anions, counterbalanced
      by electron transfer toward EMIM(+) cations near the interface, revealing the
      tendency of easy ionization of Li and Li(x)-BF(4) cluster formation, coupled with
      the reduction of EMIM(+). These features are similar to those observed in the
      EMIM-BF(4) molecular adsorption, while these have been proved to occur in the
      crystal-layer adsorption. We examined the adhesive energy, wetability, and
      detailed electronic structure at the crystal/crystal interface.

PMID- 20059098
TI  - Size-dependent hydrophobic to hydrophilic transition for nanoparticles: a
      molecular dynamics study.
AB  - The physical properties of nanoscale materials often vary with their size, unlike
      the corresponding bulk material properties, which can only be changed by
      modifying the material composition. In particular, it is believed that hydration
      phenomena are length scale dependent. The manifestation of hydrophobicity over
      multiple length scales plays a crucial role in self-assembly processes such as
      protein folding and colloidal stability. In the case of particles composed of a
      bulk hydrophobic material, it is well known that the free energy of hydration
      monotonically increases with particle size. However, the size-dependent free
      energy of hydration for particles composed of a bulk hydrophilic material has not
      been studied. Here we show that the free energy of hydration is not a monotonic
      function of particle size, but rather, changes sign from positive to negative as
      the particle size increases. In other words, the particle is hydrophobic at small
      size and hydrophilic at large size. This behavior arises from a purely
      geometrical effect caused by the curvature of the particle-water interface. We
      explore the consequences of this phenomenon on colloidal stability and find that
      it dictates the shape of colloidal aggregates.

PMID- 20059099
TI  - Translational energy and state resolved observations of D and D2 thermally
      desorbing from D clusters chemisorbed on graphite.
AB  - Direct D atom desorption, as well as associative desorption of D(2) molecules are
      observed in thermal desorption from D atoms chemisorbed on a C(0001) surface by
      combining laser induced T-jumps with resonance enhanced multiphoton ionization
      detection. Bleaching curves suggest that different classes of chemisorbed D atom
      clusters are present on the initial surface. The energy resolved atomic
      desorption flux, obtained via time of flight techniques, compares favorably (via
      detailed balance) with theoretical calculations of atomic sticking. Density
      functional theory calculations of chemical processes (atomic desorption, atomic
      diffusion/cluster annealing, and associative desorption) on an extensive set of
      four atom H(D) clusters chemisorbed on C(0001) provide a good interpretation of
      the experiments. State and energy resolved D(2) desorption fluxes are compared
      with previous state averaged results. In combination with density functional
      theory calculations these measurements reveal a substantial energy loss (>1 eV)
      to the surface in the associative desorption.

PMID- 20059100
TI  - Two new colloidal crystal phases of lipid A-monophosphate: order-to-order
      transition in colloidal crystals.
AB  - A study of the structure of stable regular-shaped nanocrystals of hexa-acylated
      (C(14)) lipid A-monophosphate from Escherichia coli was carried out using dilute
      electrostatically stabilized aqueous dispersions at low ionic strength (I=1.0x10(
      5)M NaCl). An order-to-order transition of colloidal clusters of lipid A
      monophosphate was found at two volume fractions: phi=5.9x10(-4) and phi=11.5x10(
      4). The clusters belonged to the cubic space groups Pm3n and Ia3d with unit-cell
      dimensions of a=4.55 nm and a=6.35 nm, respectively, as revealed by small-angle x
      ray diffraction and electron-diffraction results of thin nanocrystals of lipid A
      monophosphate. When viewed in the scanning electron microscope these fragile
      clusters displayed a number of shapes: cubic, cylindrical, and sometimes-rounded
      hexagons, which were extremely sensitive when exposed to an electron beam. The
      smallest and most numerous of the clusters appeared as approximately 7 nm cubes.
      Crystalline cluster formation occurred over a wide volume-fraction range, between
      1.5x10(-4) and 40.0x10(-4), and at temperatures of 20 and 35 degrees C. The
      crystalline networks of the lipid A-monophosphate clusters may be represented by
      space-filling models of two pentagonal dodecahedra with six tetrakaidecahedra
      arrangements of lipid A-"micelles" in the cubic space group Pm3n. The simulated
      electron density profiles are in accord with spherical clusters of lipid A
      monophosphate at the corners and at the body centers of the cubic Pm3n unit cell.
      The profiles are rounded tetrahedrally at distances of 1/4 and 3/4 along one of
      the bisectors of each face of the cubic unit cell. These nanocrystalline systems
      provide examples of "cellular" crystalline networks, which rearrange themselves
      spontaneously into three-dimensional polyhedral structures. It appears that a
      closely related analogy exists between the tetrahedrally close-packed networks as
      revealed for the lipid A-mono- and diphosphates [C. A. Faunce, H. Reichelt, H. H.
      Paradies, et al., J. Chem. Phys. 122, 214727 (2005); C. A. Faunce, H. Reichelt,
      P. Quitschau, et al., J. Chem. Phys. 127, 115103 (2007)]. However, the cubic Ia3d
      phase consists of two three-dimensional networks of rods, mutually intertwined
      but not connected. For this cubic Ia3d phase each junction involves three
      coplanar rods at an angle of 120 degrees, showing an interwoven labyrinth of
      lipid A-monophosphate rods which are connected three by three. The rod diameter
      is approximately 2.2 nm, which is similar in diameter to the disk-shaped
      aliphatic chiral core of lipid A-monophosphate (2.14 nm) with an ellipticity of
      0.62 seen for the "c" position of the tetrakaidecahedra in the Pm3n cubic unit
      cell. An epitaxial relationship appears to exist between the {211} planes of the
      cubic Ia3d phase and the (001) planes of the lamellar phase as well as with the
      {10} planes of the hexagonal phase. The transformation of the cubic into the
      hexagonal phase can be reconciled by the growth of a cylinderlike assembly of
      lipid A-monophosphate molecules of the hexagonal phase parallel to the 111
      directions of the cubic Ia3d phase. Upon cooling from 35 to 20 degrees C the
      cubic Ia3d lipid A-monophosphate phase unexpectedly transforms and gives rise to
      an intermediate R3m structure (a=3.90+/-0.12 nm, c=7.82+/-0.05 nm, and gamma=120
      degrees). Both cubic Ia3d and hexagonal R3m phases originate from similar rodlike
      units of lipid A-monophosphate clusters. However, the overall shapes of the
      assemblies are different because of their spatial distribution. Both assemblies
      morphologically bridge the lipid A-monophosphate hexagonal and and lamellar
      phases. The structural path followed during the phase transitions is governed by
      topological similarities between the phase which forms and the one from which it
      originates. Although the two phases, Ia3d and R3m, have similar curvature
      energies on cooling, the topology is more than likely to be the initial factor
      determining the overall phase transition path.

PMID- 20059101
TI  - Dipolar electrostatic energy effect on relaxation process of monolayers at air
      water interface: analysis of thermodynamics and kinetics.
AB  - In order to understand the effect of electrostatic energy on phase transition
      from monolayer to multilayer, isobaric relaxation process of Langmuir monolayers
      composed of stearic acid or ferroelectric polyvinylidene fluoride and
      trifluoroethylene copolymer with various vinylidene fluoride (VDF) ratios is
      investigated in terms of thermodynamic and kinetic analysis. A monotonous
      decreasing tendency of material loss with respect to temperature is observed for
      stearic acid monolayer, which is due to thermal activation effect on phase
      transition from monolayer to multilayer. In contrast, for the ferroelectric
      monolayer it presents a nonmonotonous behavior of losing materials with a peak
      position near the Curie temperature, which is not only owing to thermal
      activation but also dipole moment change. This observation is confirmed for the
      copolymer monolayers with other VDF content ratios. Amazingly, for the
      ferroelectric monolayers a good correspondence is found for critical temperatures
      evaluated from several independent methods including the analysis on slow
      collapse. This finding again tells the fact that the relaxation process, namely
      phase transition from monolayer to multilayer, is greatly influenced by dipolar
      electrostatic energy. Moreover, the study of time dependent relaxation process
      reveals a diffusionlike behavior of multilayer structure formation, which cannot
      be interpreted by classical models. Hence a new model based on diffusion-driven
      material transfer is proposed and diffusivity of the copolymer molecules is
      estimated with a value of 0.4x10(-5) cm(2)/s. As a whole, this research reflects
      the importance of dipolar electrostatic energy for phase transition of monolayers
      at air-water interface.

PMID- 20059102
TI  - Dissolution dynamics of thin films measured by optical reflectance.
AB  - Measuring the dissolution dynamics of thin films in situ both with spatial and
      temporal resolution can be a challenging task. Available methods such as scanning
      electrochemical microscopy rely on scanning the specimen and are intrinsically
      slow. We developed a characterization technique employing only an optical
      microscope, a digital charge coupled device camera, and a computer for image
      processing. It is capable of detecting dissolution rates of the order of nm/min
      and has a spatial and temporal resolution which is limited by the imaging and
      recording setup. We demonstrate the capabilities of our method by analyzing the
      electrochemical dissolution of copper thin films on gold substrates in a mild
      hydrochloric acid solution. Due to its simplicity, our technique can be
      implemented in any laboratory and can be applied to a variety of systems such as
      thin film sensors or passive coatings.

PMID- 20059103
TI  - Thermal desorption of C6H6 from surfaces of astrophysical relevance.
AB  - The thermal desorption of C(6)H(6) from two astrophysically relevant surfaces has
      been studied using temperature programmed desorption. Desorption from an
      amorphous SiO(2) substrate was used as a mimic for bare interstellar grains,
      while multilayer films of amorphous solid water (ASW) were used to study the
      adsorption of C(6)H(6) on grains surrounded by H(2)O dominated icy mantles.
      Kinetic parameters were obtained through a combination of kinetic modeling,
      leading edge analysis, and by considering a distribution of binding sites on the
      substrate. The latter is shown to have a significant impact on the desorption of
      small exposures of C(6)H(6) from the amorphous SiO(2) substrate. In the case of
      adsorption on ASW, dewetting behavior and fractional order desorption at low
      coverage strongly suggest the formation of islands of C(6)H(6) on the H(2)O
      surface. The astrophysical implications of these observations are briefly
      outlined.

PMID- 20059104
TI  - Quantum transport in alkane molecular wires: effects of binding modes and
      anchoring groups.
AB  - Effects of binding modes and anchoring groups on nonequilibrium electronic
      transport properties of alkane molecular wires are investigated from atomic first
      principles based on density functional theory and nonequilibrium Green's function
      formalism. Four typical binding modes, top, bridge, hcp-hollow, and fcc-hollow,
      are considered at one of the two contacts. For wires with three different
      anchoring groups, dithiol, diamine, or dicarboxylic acid, the low bias
      conductances resulting from the four binding modes are all found to have either a
      high or a low value, well consistent with recent experimental observations. The
      trend can be rationalized by the behavior of electrode-induced gap states at
      small bias. When bias increases to higher values, states from the anchoring
      groups enter into the bias window and contribute significantly to the tunneling
      process so that transport properties become more complicated for the four binding
      modes. Other low bias behaviors including the values of the inverse length scale
      for tunneling characteristic, contact resistance, and the ratios of the high/low
      conductance values are also calculated and compared to experimental results. The
      conducting capabilities of the three anchoring groups are found to decrease from
      dithiol, diamine to dicarboxylic-acid, largely owing to a decrease in binding
      strength to the electrodes. Our results give a clear microscopic picture to the
      transport physics and provide reasonable qualitative explanations for the
      corresponding experimental data.

PMID- 20059105
TI  - Thermodynamic line tension of a molecular solid.
AB  - For a molecular solid with dispersion forces, a particular expression is derived
      relating thermodynamic line tension to thermodynamic surface tension and the
      crystal spacing. Using recent data on the local Irving-Kirkwood stress tensor at
      the slit edge, local surface tension near the crystal edge and the line tension
      of the edge are estimated. This is the first estimation of the thermodynamic line
      tension for a molecular cubic crystal in the literature.

PMID- 20059107
TI  - Monte Carlo determination of mixed electrolytes next to a planar dielectric
      interface with different surface charge distributions.
AB  - Employing canonical ensemble Monte Carlo simulations, we report a calculation of
      the distribution of small ions next to a planar negatively charged surface in the
      presence of mixed electrolytes of monovalent and trivalent salt ions within the
      framework of the primitive model under more realistic hydrated ion size
      conditions. The effects of surface charge discreteness and dielectric breakdown
      on charge inversion are discussed based on increasing concentration of both
      monovalent and trivalent salt. Moreover, a comparison of the simulation results
      for different discretization models is made along with the case of uniformly
      distributed charge in terms of the ionic density profiles as well as the
      integrated charge distribution function. For finite size charged groups located
      inside the lower dielectric region, a complete equivalence with the case of
      uniform distribution is observed if the quantities of interest are exclusively
      analyzed as a function of the distance to the charged interface. With protruding
      head groups into the aqueous solution, the excluded volume dominates over the
      correlation effect, therefore the ions are less accumulated in the vicinity of
      the charged surface, inducing that the onset position of charge inversion
      experiences an evident shift toward the aqueous environment. Overall, the effect
      of repulsive image forces on the diffuse double layer structure can be
      significant at low surface charge density irrespectively of surface charge
      distributions.

PMID- 20059106
TI  - Analysis of anisotropic local field in sum frequency generation spectroscopy with
      the charge response kernel water model.
AB  - A new flexible and polarizable water model based on the charge response kernel
      (CRK) theory is developed for the analysis of sum frequency generation (SFG)
      spectroscopy. The CRK model well describes several bulk water properties and SFG
      spectrum by molecular dynamics (MD) calculations. While the flexible and
      polarizable MD simulation generally adopts the short-range damping of
      intermolecular interaction, it is found that the same procedure is not adequate
      for the calculation of transition dipole in strongly hydrogen bonding
      environment. Accordingly, the improved calculation of the nonlinear
      susceptibility of water surface results in the positive imaginary part in the
      3000-3200 cm(-1) region, which is consistent with recent phase-sensitive
      experiments. The mechanism of the positive region is attributed to the
      anisotropic local field effect induced by the orientational correlation of
      surface water.

PMID- 20059108
TI  - X-ray spectroscopy studies on the surface structural characteristics and
      electronic properties of platinum nanoparticles.
AB  - The surface structural characteristics and electronic behavior of three platinum
      nanoparticle (NP) samples prepared with tertiary amine (Pt-TA), primary amine (Pt
      PA), and thiol (Pt-SR) molecules were studied using Pt 4f, 5d, and S 2p x-ray
      photoelectron spectroscopy (XPS), Pt L(3)-edge x-ray absorption spectroscopy
      (XAS), and theoretical projected local density of states (l-DOS) calculations.
      Transmission electron microscopy and XPS composition analysis indicated that the
      three NPs were all very small (1-2 nm), the NP size decreasing in the order of Pt
      TA>Pt-PA approximately Pt-SR. All the three samples showed a positive Pt 4f
      binding energy (BE) shift relative to that of the bulk, in the order of bulk<Pt
      TA<Pt-PA<Pt-SR. The origin of the BE shift was elucidated by XAS and
      deconvolution of the Pt 4f XPS peak, indicating that the observed BE shifts were
      largely associated with the initial state effect (i.e., nanosize and surface
      structure). The surface and size effects on the electronic behavior of Pt were
      further studied by valence band XPS and the results were interpreted with
      calculated d-DOS of three Pt(55) model clusters with varied surface structures.
      Finally, the implication of these results on tuning the electronic properties of
      Pt NPs with size, surface, and alloying effects was discussed.

PMID- 20059109
TI  - Strain hardening in bidisperse polymer glasses: separating the roles of chain
      orientation and interchain entanglement.
AB  - The effects of entanglement and chain orientation on strain hardening in glassy
      polymers are separated by examining mixtures of chains with different lengths.
      Simulations show that the orientation of a molecule of a given chain length is
      the same in monodisperse systems and bidisperse mixtures, even when entangled and
      unentangled chains are mixed. In addition, the stress in mixtures is equal to the
      weighted average of the stresses in monodisperse systems. These results indicate
      that chains contribute independently to strain hardening, that chain orientation
      is determined by local interactions with the surrounding glass, and that
      entanglements play at most an indirect role in strain hardening in the range of
      strains typically studied. We discuss these results in the context of recent
      theories.

PMID- 20059110
TI  - Canonical and microcanonical analysis of nongrafted homopolymer adsorption by an
      attractive substrate.
AB  - Using the off-lattice Monte Carlo simulation and replica-exchange method, we
      studied the behavior of nongrafted homopolymer adsorption by an attractive
      substrate from both the canonical and the microcanonical views. An adsorption
      transition is identified from the peak in canonical specific heat and compared
      with the conventional polymer adsorption with one end anchored on the surface of
      the substrate. Judging from the typical "backbending effect" and the negative
      specific heat in microcanonical ensemble, the transition is first-order-like when
      adsorption is relatively strong. However, it becomes second-order-like when the
      strength of adsorption becomes weak enough. Further study reveals that for a
      chain consisting of a limited number of monomers, the type of this transition
      becoming either first- or second-order-like depends not only on the interplay
      between monomer-monomer and monomer-substrate interaction, but also on the width
      of the gap in which it is confined.

PMID- 20059111
TI  - Phase equilibria in polymer blend thin films: a Hamiltonian approach.
AB  - We propose a Hamiltonian formulation of the Flory-Huggins-de Gennes theory
      describing a polymer blend thin film. We then focus on the case of 50:50 polymer
      blends confined between antisymmetric walls. The different phases of the system
      and the transitions between them, including finite-size effects, are
      systematically studied through their relation with the geometry of the
      Hamiltonian flow in phase space. This method provides an easy and efficient way,
      with strong graphical insight, to infer the qualitative physical behavior of
      polymer blend thin films.

PMID- 20059112
TI  - Nanoparticle aggregation in the presence of a block copolymer.
AB  - By employing dissipative particle dynamics simulations, we investigated the
      cooperative phase behavior of composites containing diblock copolymer molecules
      and nanoparticles. The nanoparticles and their aggregates are located either in
      the domains generated by each of the two kinds of segments of the block copolymer
      and/or at their interface. Various conditions, such as the interactions between
      nanoparticles, the interactions between them and the segments of the block
      copolymer, the interactions between the segments of the block copolymer, and the
      volume ratio of nanoparticles to block copolymer, have been changed to gather
      information about nanoparticle aggregation and block copolymer/nanoparticles
      morphology building. The dynamics of nanoparticles aggregation and the evolution
      of the morphology of the block copolymer have been followed. Our findings have
      identified two critical repulsive interactions regarding nanoparticle
      aggregation, one between nanoparticles and the other between the segments of the
      block copolymer and nanoparticles. Aggregates have been generated for repulsive
      interactions larger than the former critical value or smaller than the latter
      one.

PMID- 20059113
TI  - Two perspectives on the twist of DNA.
AB  - Because of the double-helical structure of DNA, in which two strands of
      complementary nucleotides intertwine around each other, a covalently closed DNA
      molecule with no interruptions in either strand can be viewed as two interlocked
      single-stranded rings. Two closed space curves have long been known by
      mathematicians to exhibit a property called the linking number, a topologically
      invariant integer, expressible as the sum of two other quantities, the twist of
      one of the curves about the other, and the writhing number, or writhe, a measure
      of the chiral distortion from planarity of one of the two closed curves. We here
      derive expressions for the twist of supercoiled DNA and the writhe of a closed
      molecule consistent with the modern view of DNA as a sequence of base-pair steps.
      Structural biologists commonly characterize the spatial disposition of each step
      in terms of six rigid-body parameters, one of which, coincidentally, is also
      called the twist. Of interest is the difference in the mathematical properties
      between this step-parameter twist and the twist of supercoiling associated with a
      given base-pair step. For example, it turns out that the latter twist, unlike the
      former, is sensitive to certain translational shearing distortions of the
      molecule that are chiral in nature. Thus, by comparing the values for the two
      twists for each step of a high-resolution structure of a protein-DNA complex, we
      may be able to determine how the binding of various proteins contributes to
      chiral structural changes of the DNA.

PMID- 20059114
TI  - One-dimensional confinement of electric field and humidity dependent DNA
      conductivity.
AB  - The dependence of DNA assemblies conductance on relative humidity is investigated
      theoretically. Following earlier suggestions, we consider the ionic conductivity
      through the layers of water adsorbed by DNA molecules. The increase in humidity
      results in a growing water layer. The binding energy of ions depends on the
      thickness of the water layer due to change in water polarization. This dependence
      is very strong at smaller thicknesses of water layers due to the low-dimensional
      confinement of an electric field in water. We show that the associated change in
      ion concentration can explain the six orders of magnitude increase in
      conductivity, with relative humidity growing from 0.05 to 0.95.

PMID- 20059115
TI  - Low-frequency vibrational properties of lysozyme in sugar aqueous solutions: a
      Raman scattering and molecular dynamics simulation study.
AB  - The low-frequency (omega<400 cm(-1)) vibrational properties of lysozyme in
      aqueous solutions of three well-known protecting sugars, namely, trehalose,
      maltose, and sucrose, have been investigated by means of complementary Raman
      scattering experiments and molecular dynamics simulations. The comparison of the
      Raman susceptibility chi(")(omega) of lysozyme/water and lysozyme/sugar/water
      solutions at a concentration of 40 wt % with the chi(") of dry lysozyme suggests
      that the protein dynamics mostly appears in the broad peak around 60-80 cm(-1)
      that reflects the vibrations experienced by atoms within the cage formed by their
      neighbors, whereas the broad shoulder around 170 cm(-1) mainly stems from the
      intermolecular O-H...O stretching vibrations of water. The addition of sugars
      essentially induces a significant high frequency shift and intensity reduction of
      this band that reveal a slowing down of water dynamics and a distortion of the
      tetrahedral hydrogen bond network of water, respectively. Furthermore, the
      lysozyme vibrational densities of states (VDOS) have been determined from
      simulations of lysozyme in 37-60 wt % disaccharide aqueous solutions. They
      exhibit an additional broad peak around 290 cm(-1), in line with the VDOS of
      globular proteins obtained in neutron scattering experiments. The influence of
      sugars on the computed VDOS mostly appears on the first peak as a slight high
      frequency shift and intensity reduction in the low-frequency range (omega<50 cm(
      1)), which increase with the sugar concentration and with the exposition of
      protein residues to the solvent. These results suggest that sugars stiffen the
      environment experienced by lysozyme atoms, thereby counteracting the softening of
      protein vibrational modes upon denaturation, observed at high temperature in the
      Raman susceptibility of the lysozyme/water solution and in the computed VDOS of
      unfolded lysozyme in water. Finally, the Raman susceptibility of sugar/water
      solutions and the calculated VDOS of water in the different lysozyme solutions
      confirm that sugars induce a significant strengthening of the hydrogen bond
      network of water that may stabilize proteins at high temperatures.

PMID- 20059116
TI  - Comprehensive physical mechanism of two-headed biomotor myosin V.
AB  - Two-headed biomotor myosin V autonomously coordinates its two identical heads in
      fuel consumption and mechanical stepping, so that the dimerized motor as a whole
      gains the capability of processive, unidirectional movement along cytoskeletal
      filament. How the dimer-level functions like sustained direction rectification
      and autonomous coordination emerge out of physical principles poses an
      outstanding question pertinent to motor protein biology as well as the nascent
      field of bioinspired nanomotors. Here the comprehensive physical mechanism for
      myosin V motor is identified by a dimer-level free-energy analysis that is
      methodologically calibrated against experimental data. A hallmark of the
      identified mechanism is a mechanically mediated symmetry breaking that occurs at
      the dimer level and prevails against ubiquitous thermal fluctuations. Another
      character is the onset of substantial free-energy gaps between major dimer-track
      binding configurations. The symmetry breaking is the basis for myosin V's
      directional rectification, and the energy gaps facilitate autonomous head-head
      coordination. The mechanism explains the experimental finding that myosin V makes
      ATP-independent consecutive steps under high opposing loads but not under pushing
      loads. Interestingly, myosin V and another major biomotor kinesin 1 are found to
      share essentially the same core mechanism but for distinctly different working
      regimes.

PMID- 20059117
TI  - Lymphotactin: how a protein can adopt two folds.
AB  - Metamorphic proteins such as lymphotactin are a notable exception of the
      empirical principle that structured natural proteins possess a unique three
      dimensional structure. In particular, the human chemokine lymphotactin protein
      exists in two distinct conformations (one monomeric and one dimeric) under
      physiological conditions. In this work, we use a C(alpha) Go model to show how
      this very peculiar behavior can be reproduced. From the study of the
      thermodynamics and of the kinetics, we characterize the interconversion
      mechanism. In particular, this takes place through the docking of the two chains
      living in a third monomeric, partially unfolded, state which shows a residual
      structure involving a set of local contacts common to the two native
      conformations. The main feature of two fold proteins appears to be the sharing of
      a common set of local contacts between the two distinct folds as confirmed by the
      study of two designed two fold proteins. Metamorphic proteins may be more common
      than expected.

PMID- 20059118
TI  - Multiscale network model for large protein dynamics.
AB  - Protein dynamics is essential for gaining insight into biological functions of
      proteins. Although protein dynamics is well delineated by molecular model, the
      molecular model is computationally prohibited for simulating large protein
      structures. In this work, we provide a multiscale network model (MNM) that allows
      the efficient computation on low-frequency normal modes related to structural
      deformation of proteins as well as dynamic behavior of functional sites.
      Specifically, MNM consists of two regions, one of which is described as a low
      resolution structure, while the other is dictated by a high-resolution structure.
      The high-resolution regions using all alpha carbons of the protein are mainly
      binding site parts, which play a critical function in molecules, while the low
      resolution parts are constructed from a further coarse-grained model (not using
      all alpha carbons). The feasibility of MNM to observe the cooperative motion of a
      protein structure was validated. It was shown that the MNM enables us to
      understand functional motion of proteins with computational efficiency.

PMID- 20059119
TI  - Stochastic simulations of cargo transport by processive molecular motors.
AB  - We use stochastic computer simulations to study the transport of a spherical
      cargo particle along a microtubule-like track on a planar substrate by several
      kinesin-like processive motors. Our newly developed adhesive motor dynamics
      algorithm combines the numerical integration of a Langevin equation for the
      motion of a sphere with kinetic rules for the molecular motors. The Langevin part
      includes diffusive motion, the action of the pulling motors, and hydrodynamic
      interactions between sphere and wall. The kinetic rules for the motors include
      binding to and unbinding from the filament as well as active motor steps. We find
      that the simulated mean transport length increases exponentially with the number
      of bound motors, in good agreement with earlier results. The number of motors in
      binding range to the motor track fluctuates in time with a Poissonian
      distribution, both for springs and cables being used as models for the linker
      mechanics. Cooperativity in the sense of equal load sharing only occurs for high
      values for viscosity and attachment time.

PMID- 20059120
TI  - Are pressure fluctuation-based equilibrium methods really worse than
      nonequilibrium methods for calculating viscosities?

PMID- 20059125
TI  - Application of a simple asynchronous mechanical light chopper to multielectron
      coincidence spectroscopy.
AB  - A simple asynchronous mechanical light chopper, based on modification of a turbo
      molecular pump, has been developed to extend the interval between light pulses in
      single bunch operation at the Photon Factory storage ring. A pulse repetition
      rate of 80 kHz was achieved using a cylinder rotating at 48000 rpm, with 100
      slits of 80 microm width. This allows absolute timing of particles up to 12.48
      micros instead of the single-bunch period of 624 ns. We have applied the chopper
      together with a light pulse monitor to measure multielectron coincidence spectra
      using a magnetic bottle time-of-flight electron spectrometer. With such a system,
      the electron energies are determined without any ambiguity, the folding of
      coincidence spectra disappears and the effect of false coincidences is
      drastically reduced.

PMID- 20059126
TI  - Solid and liquid spectroscopic analysis (SALSA)--a soft x-ray spectroscopy
      endstation with a novel flow-through liquid cell.
AB  - We present a novel synchrotron endstation with a flow-through liquid cell
      designed to study the electronic structure of liquids using soft x-ray
      spectroscopies. In this cell, the liquid under study is separated from the vacuum
      by a thin window membrane, such that the sample liquid can be investigated at
      ambient pressure. The temperature of the probing volume can be varied in a broad
      range and with a fast temperature response. The optimized design of the cell
      significantly reduces the amount of required sample liquid and allows the use of
      different window membrane types necessary to cover a broad energy range. The
      liquid cell is integrated into the solid and liquid spectroscopic analysis
      (SALSA) endstation that includes a high-resolution, high-transmission x-ray
      spectrometer and a state-of-the-art electron analyzer. The modular design of
      SALSA also allows the measurement of solid-state samples. The capabilities of the
      liquid cell and the x-ray spectrometer are demonstrated using a resonant
      inelastic x-ray scattering map of a 25 wt % NaOD solution.

PMID- 20059127
TI  - Resonant photoacoustic cell for pulsed laser analysis of gases at high
      temperature.
AB  - A new approach to high temperature gas analysis by means of photoacoustic (PA)
      spectroscopy is presented. The transverse modes of the resonant PA cell were
      excited with a pulsed laser and detected with a microphone. Changes in the
      properties of the PA cell resulting from a varying temperature are discussed and
      considered when processing the PA signal. The feasibility of the proposed method
      was demonstrated by studying PA response from saturated vapor of potassium
      chloride (KCl) in the temperature range extending from 410 to 691 degrees C. The
      PA spectrum, the detection limit, and the signal saturation of KCl vapor are
      discussed. At 245 nm excitation wavelength and 300 microJ pulse energy, the
      achieved detection limit for KCl is 15 ppb.

PMID- 20059128
TI  - Frequency-agile terahertz-wave parametric oscillator in a ring-cavity
      configuration.
AB  - We demonstrate a frequency-agile terahertz wave parametric oscillator (TPO) in a
      ring-cavity configuration (ring-TPO). The TPO consists of three mirrors and a
      MgO:LiNbO(3) crystal under noncollinear phase-matching conditions. A novel, fast
      frequency-tuning method was realized by controlling a mirror of the three-mirror
      ring cavity. The wide tuning range between 0.93 and 2.7 THz was accomplished. For
      first demonstration using the ring-TPO, terahertz spectroscopy was performed as
      the verification of the frequency-agile performance, measuring the transmission
      spectrum of the monosaccharide glucose. The spectrum was obtained within about 8
      s in good comparison to those of Fourier transform infrared spectrometer.

PMID- 20059129
TI  - Absolute density-profile tomography of molecular beams using multiphoton
      ionization.
AB  - We describe an approach for the absolute density measurement of rotationally
      symmetric molecular beams via multiphoton ionization. This simple single
      projection tomographic technique requires only knowledge of the spatial intensity
      profile and ionization characteristics of the focused laser beam that probes the
      pulsed molecular jet. Multiphoton ionization (MPI) of a xenon beam allowed
      tomographic reconstruction of a two-dimensional density profile with a peak
      density of (4.2+/-0.4)x10(18) m(-3), which was compared with the theoretical
      predictions of the sudden freeze model. An analytic solution to the Abel
      transform is derived for Gaussian projected density profiles which greatly
      simplifies the reconstruction of the absolute radial density. MPI is sufficiently
      general that this technique can be readily applied to atomic beams with a broad
      range of chemistries.

PMID- 20059130
TI  - Frequency-resolved optical gating system with a tellurium crystal for
      characterizing free-electron lasers in the wavelength range of 10-30 microm.
AB  - A second-harmonic generation frequency-resolved optical gating (SHG-FROG) system
      has been developed for the complete characterization of laser pulses in the
      wavelength range of 10-30 microm. A tellurium crystal is used so that spectrally
      resolved autocorrelation signals with a good signal-to-noise ratio are obtained.
      Pulses (wavelength approximately 22 microm) generated from a free-electron laser
      are measured by the SHG-FROG system. The SHG intensity profile and the spectrum
      obtained by FROG measurements are well consistent with those of independent
      measurements of the pulse length and spectrum. The pulse duration and spectral
      width determined from the FROG trace are 0.6 ps and 5.2 THz at full width half
      maximum, respectively.

PMID- 20059131
TI  - Interferometric polarization pulse shaper stabilized by an external laser diode
      for arbitrary vector field shaping.
AB  - We achieved reliable and stable generation of pulses with all possible
      polarization states by a Mach-Zehnder pulse shaper. This was realized by
      incorporating a stabilization mechanism using an external laser diode in the
      interferometric pulse shaper. This stabilization mechanism has overcome an
      inherent instability in the Mach-Zehnder interferometer, which caused serious
      distortion of shaped pulses. For a demonstration of polarization shaping, we
      generated and measured chiral pulses with a rotating major axis of polarizing
      orientations at arbitrary frequencies. We expect these chiral pulses enables us
      to study on new chirality-related light-matter interactions.

PMID- 20059132
TI  - Collinear laser spectroscopy of francium using online rubidium vapor
      neutralization and amplitude modulated lasers.
AB  - Performing collinear laser spectroscopy on low intensity radioactive beams
      requires sensitive detection techniques. We explain our apparatus to detect
      atomic resonances in neutralized (208-210)Fr ion beams at beam energies of 5 keV
      and intensities of 10(5) s(-1). Efficient neutralization (> or = 80%) is
      accomplished by passing the beam through a dense Rb vapor. Increased detection
      efficiency is achieved by amplitude modulating the exciting laser to decrease the
      scattered light background, allowing fluorescence detection only when the laser
      is near its minimum in the modulation cycle. Using this technique in a collinear
      geometry we achieve a background reduction by a factor of 180 and a signal-to
      noise increase of 2.2, with the lifetime of the atomic state playing a role in
      the efficiency of this process. Such laser modulation will also produce sidebands
      on the atomic spectra which we illustrate.

PMID- 20059133
TI  - Time-delay compensated monochromator for the spectral selection of extreme
      ultraviolet high-order laser harmonics.
AB  - The design and the characterization of a monochromator for the spectral selection
      of ultrashort high-order laser harmonics in the extreme ultraviolet are
      presented. The instrument adopts the double-grating configuration to preserve the
      length of the optical paths of different diffracted rays, without altering the
      extremely short duration of the pulse. The gratings are used in the off-plane
      mount to have high efficiency. The performances of the monochromator have been
      characterized in terms of spectral response, efficiency, photon flux, imaging
      properties, and temporal response. In particular, the temporal characterization
      of the harmonic pulses has been obtained using a cross-correlation method: Pulses
      as short as 8 fs have been measured at the output of the monochromators,
      confirming the effectiveness of the time-delay compensated configuration.

PMID- 20059134
TI  - Multipurpose furnace for in situ studies of polycrystalline materials using
      synchrotron radiation.
AB  - We report a multipurpose furnace designed for studies using synchrotron radiation
      on polycrystalline materials, namely, metals, ceramics, and (semi)crystalline
      polymers. The furnace has been designed to carry out three-dimensional (3D) x-ray
      diffraction measurements but can also be used for other types of synchrotron
      radiation research. The furnace has a very low thermal gradient across the
      specimen (<0.2 degrees C/mm). Accurate determination of the temperature can be
      carried out by welding a thermocouple to the specimen. The furnace can be rotated
      over an angle of 90 degrees in order to determine the crystallographic
      orientation of each individual grain. It is possible to follow growth kinetics of
      all grains in the illuminated volume of the specimen. The specimen environment
      can be controlled varying from vacuum (up to 10(-5) mbar) to gas or air filled.
      The maximum temperature of operation is 1500 degrees C, with the possibility of
      achieving high heating (up to 20 degrees C/s) and cooling rates (up to 30 degrees
      C/s without quenching gas). 3D maps of the microstructure of the specimen can be
      generated at elevated temperatures by bringing the high-resolution detector close
      to the specimen. We show an example of a simulation of the heat affected zone
      during the thermal cycle of a weld in a transformation-induced plasticity steel
      carried out using the furnace. The unique characteristics of the furnace open
      possibility of new fields in materials research using synchrotron radiation.

PMID- 20059135
TI  - The quality factor of a superconducting rf resonator in a magnetic field.
AB  - The quality factor of a superconducting NbTi resonator at 1.6 MHz in a magnetic
      field up to 1.2 T as well as its temperature dependence is investigated. A
      hysteresis effect in the superconducting surface resistance as a function of the
      magnetic field is observed. An unloaded Q-value of the resonator of 40,500 is
      achieved at 3.9 K. It is shown that this Q-value is limited by dielectric losses
      in the FORMVAR insulation of the coils wire. The details of the Q-value
      optimization are discussed. In the temperature dependence of the Q-value a steep
      decrease is observed above T approximately = 7.5 K. Finally, the implications of
      these measurements for real trap experiments are discussed in detail.

PMID- 20059136
TI  - A new particle size analyzer.
AB  - A new particle sizer which integrates the dispersion and detection parts is
      presented. Particles are dispersed based on charging between two parallel plates
      connected to a high voltage power source. The charged particles bounce between
      the two plates and escape into a measuring area where the size is determined by
      light scattering. The instrument is calibrated using standard powders. The data
      obtained from the new instrument are in good agreement with those obtained from a
      commercial particle size analyzer. The sizer works both for insulator and
      conductive powders.

PMID- 20059137
TI  - Observation of pulsed x-ray trains produced by laser-electron Compton
      scatterings.
AB  - X-ray generation based on laser-electron Compton scattering is one attractive
      method to achieve a compact laboratory-sized high-brightness x-ray source. We
      have designed, built, and tested such a source; it combines a 50 MeV multibunch
      electron linac with a mode-locked 1064 nm laser stored and amplified in a Fabry
      Perot optical cavity. We directly observed trains of pulsed x rays using a
      microchannel plate detector; the resultant yield was found to be 1.2x10(5) Hz in
      good agreement with prediction. We believe that the result has demonstrated good
      feasibility of linac-based compact x-ray sources via laser-electron Compton
      scatterings.

PMID- 20059138
TI  - High intensity electron cyclotron resonance proton source for low energy high
      intensity proton accelerator.
AB  - Electron cyclotron resonance (ECR) proton source at 50 keV, 50 mA has been
      designed, developed, and commissioned for the low energy high intensity proton
      accelerator (LEHIPA). Plasma characterization of this source has been performed.
      ECR plasma was generated with 400-1100 W of microwave power at 2.45 GHz, with
      hydrogen as working gas. Microwave was fed in the plasma chamber through quartz
      window. Plasma density and temperature was studied under various operating
      conditions, such as microwave power and gas pressure. Langmuir probe was used for
      plasma characterization using current voltage variation. The typical hydrogen
      plasma density and electron temperature measured were 7x10(11) cm(-3) and 6 eV,
      respectively. The total ion beam current of 42 mA was extracted, with three
      electrode extraction geometry, at 40 keV of beam energy. The extracted ion
      current was studied as a function of microwave power and gas pressure. Depending
      on source pressure and discharge power, more than 30% total gas efficiency was
      achieved. The optimization of the source is under progress to meet the
      requirement of long time operation. The source will be used as an injector for
      continuous wave radio frequency quadrupole, a part of 20 MeV LEHIPA. The required
      rms normalized emittance of this source is less than 0.2 pi mm mrad. The
      simulated value of normalized emittance is well within this limit and will be
      measured shortly. This paper presents the study of plasma parameters, first beam
      results, and the status of ECR proton source.

PMID- 20059139
TI  - Three-dimensional photogrammetric measurement of magnetic field lines in the WEGA
      stellarator.
AB  - The magnetic confinement of plasmas in fusion experiments can significantly
      degrade due to perturbations of the magnetic field. A precise analysis of the
      magnetic field in a stellarator-type experiment utilizes electrons as test
      particles following the magnetic field line. The usual fluorescent detector for
      this electron beam limits the provided information to two-dimensional cut views
      at certain toroidal positions. However, the technique described in this article
      allows measuring the three-dimensional structure of the magnetic field by means
      of close-range photogrammetry. After testing and optimizing the main diagnostic
      components, measurements of the magnetic field lines were accomplished with a
      spatial resolution of 5 mm. The results agree with numeric calculations,
      qualifying this technique as an additional tool to investigate magnetic field
      configurations in a stellarator. For a possible future application, ways are
      indicated on how to reduce experimental error sources.

PMID- 20059140
TI  - Compact multiwire proportional counters for the detection of fission fragments.
AB  - Two large area multistep position sensitive (two dimensional) multiwire
      proportional counters have been developed for experiments involving study of
      fission dynamics using general purpose scattering chamber facility at IUAC. Both
      detectors have an active area of 20x10 cm(2) and provide position signals in
      horizontal (X) and vertical (Y) planes, timing signal for time of flight
      measurements and energy signal giving the differential energy loss in the active
      volume. The design features are optimized for the detection of low energy heavy
      ions at very low gas pressures. Special care was taken in setting up the readout
      electronics, constant fraction discriminators for position signals in particular,
      to get optimum position and timing resolutions along with high count rate
      handling capability of low energy heavy ions. A custom made charge sensitive
      preamplifier, having lower gain and shorter decay time, has been developed for
      extracting the differential energy loss signal. The position and time resolutions
      of the detectors were determined to be 1.1 mm full width at half maximum (FWHM)
      and 1.7 ns FWHM, respectively. The detector could handle heavy ion count rates
      exceeding 20 kHz without any breakdown. Time of flight signal in combination with
      differential energy loss signal gives a clean separation of fission fragments
      from projectile and target like particles. The timing and position signals of the
      detectors are used for fission coincidence measurements and subsequent extraction
      of their mass, angular, and total kinetic energy distributions. This article
      describes systematic study of these fission counters in terms of efficiency, time
      resolution, count rate handling capability, position resolution, and the readout
      electronics. The detector has been operated with both five electrode geometry and
      four electrode geometry, and a comparison has been made in their performances.

PMID- 20059141
TI  - Flexible CO2 laser system for fundamental research related to an extreme
      ultraviolet lithography source.
AB  - A CO(2) laser system with flexible parameters was developed for fundamental
      research related to an extreme ultraviolet (EUV) lithography source. The laser is
      a master oscillator and power amplifier (MOPA) system, consisting of a master
      oscillator, an externally triggered plasma switch, a preamplifier, a main
      amplifier, and electronic synchronization units. The laser pulse duration can be
      varied easily from 10 to 110 ns, with a constant peak power for pulse durations
      from 25 to 110 ns. The MOPA laser system can also be operated in dual-oscillator
      mode to produce laser pulse with pulse duration as long as 200 ns and a train of
      laser pulses with flexible interval. The divergence of the laser beam is 1.3
      times the diffraction limit. The laser intensity on the target surface can be up
      to 8x10(10) W/cm(2). Utilizing this CO(2) MOPA laser system, high conversion
      efficiency from laser to in-band (2% bandwidth) 13.5 nm EUV emission has been
      demonstrated over a wide range of laser pulse durations.

PMID- 20059142
TI  - Hybrid radio-frequency/direct-current plasma-enhanced chemical vapor deposition
      system for deposition on inner surfaces of polyethylene terephthalate bottles.
AB  - A hybrid radio-frequency (rf)/direct-current (dc) system has been developed to
      control the biasing effects during deposition of diamondlike carbon (DLC) films
      onto the inner wall of polyethylene terephthalate (PET) bottles. An additional dc
      bias is coupled to the rf electrode to produce the effect of equivalent rf self
      biasing. This allows more flexible control of the deposition of the DLC films
      which are intended to improve the gas barrier characteristics. The experimental
      results demonstrate that the additional dc bias improves the adhesion strength
      between the DLC film and PET, although the enhancement in the gas barrier
      properties is not significantly larger compared to the one without dc bias. The
      apparatus and methodology have practical importance in the food and beverage
      industry.

PMID- 20059143
TI  - Axial x-ray backlighting of wire-array Z-pinches using X pinches.
AB  - For the first time, a geometry has been developed to allow for an axial imaging
      system for wire-array Z-pinch experiments that produce high-resolution x-ray
      images. The new geometry required a significant redesign of the electrode
      hardware. Calibrated areal density measurements of the Z-pinch plasma including
      wire cores, coronal plasma, streaming plasma, and the precursor were obtained.
      The system used eight-wire molybdenum (Mo) X pinches in series with and directly
      below the Z-pinch axis to provide micron-scale x-rays sources for point
      projection radiography. The images formed on the x-ray sensitive film had a 15 mm
      diameter field of view at the center height of the array and a magnification of
      about 7.5:1. Titanium (Ti) filters in front of the film transmitted radiation in
      the spectral range of 3-5 keV. For calibration, a separate film with the same
      thickness Ti filter was placed the same distance from the X pinch. This film had
      an unobstructed path that bypasses the Z-pinch but included step wedges for
      calibration of the Z-pinch plasma. The step wedges had thicknesses of tungsten
      (W) ranging from 0.015 to 1.1 microm to obtain areal density measurements of the
      W plasma from the wire-array. Images had subnanosecond temporal resolution and
      about 10 microm spatial resolution.

PMID- 20059144
TI  - A high resolution Mirnov array for the Mega Ampere Spherical Tokamak.
AB  - Over the past two decades, the increase in neutral-beam heating and alpha
      particle production in magnetically confined fusion plasmas has led to an
      increase in energetic particle driven mode activity, much of which has an
      electromagnetic signature which can be detected by the use of external Mirnov
      coils. Typically, the frequency and spatial wave number band of such oscillations
      increase with increasing injection energy, offering new challenges for diagnostic
      design. In particular, as the frequency approaches the megahertz range, care must
      be taken to model the stray capacitance of the coil, which limits the resonant
      frequency of the probe; model transmission line effects in the system, which if
      unchecked can produce system resonances; and minimize coil conductive shielding,
      so as to minimize skin currents which limit the frequency response of the coil.
      As well as optimizing the frequency response, the coils should also be positioned
      to confidently identify oscillations over a wide wave number band. This work,
      which draws on new techniques in stray capacitance modeling and coil positioning,
      is a case study of the outboard Mirnov array for high-frequency acquisition in
      the Mega Ampere Spherical Tokamak, and is intended as a roadmap for the design of
      high frequency, weak field strength magnetic diagnostics.

PMID- 20059145
TI  - A benchtop, ultrafast infrared spectroscopic imaging system for biomedical
      applications.
AB  - We discuss the potential biomedical applications for a novel infrared
      spectroscopic microimaging system. A tunable, table top solid-state laser has
      been coupled to a commercial infrared microscope, fitted with a modified high
      resolution infrared camera, to create a unique tool for midinfrared imaging. The
      system is capable of performing broadband imaging at a diffraction-limited
      spatial resolution, as is demonstrated here by spatially resolved spectroscopy of
      polymer test samples with a spectral resolution of 20 cm(-1). The large pulse
      energies (tens of microjoules) offer previously unobtainable combinations of high
      signal-to-noise levels and rapid data collection times which are superior to
      current stand-alone laboratory instruments by many decades. Coupled with the
      short (100 ps) short pulse duration, these characteristics promise to make a wide
      range of time-resolved and reflection mode imaging experiments possible with live
      biological systems.

PMID- 20059146
TI  - Photoemission electron microscopy using extreme ultraviolet attosecond pulse
      trains.
AB  - We report the first experiments carried out on a new imaging setup, which
      combines the high spatial resolution of a photoemission electron microscope
      (PEEM) with the temporal resolution of extreme ultraviolet (XUV) attosecond pulse
      trains. The very short pulses were provided by high-harmonic generation and used
      to illuminate lithographic structures and Au nanoparticles, which, in turn, were
      imaged with a PEEM resolving features below 300 nm. We argue that the spatial
      resolution is limited by the lack of electron energy filtering in this particular
      demonstration experiment. Problems with extensive space charge effects, which can
      occur due to the low probe pulse repetition rate and extremely short duration,
      are solved by reducing peak intensity while maintaining a sufficient average
      intensity to allow imaging. Finally, a powerful femtosecond infrared (IR) beam
      was combined with the XUV beam in a pump-probe setup where delays could be varied
      from subfemtoseconds to picoseconds. The IR pump beam could induce multiphoton
      electron emission in resonant features on the surface. The interaction between
      the electrons emitted by the pump and probe pulses could be observed.

PMID- 20059147
TI  - Simple and efficient scanning tunneling luminescence detection at low
      temperature.
AB  - We have designed and built an optical system to collect light that is generated
      in the tunneling region of a low-temperature scanning tunneling microscope. The
      optical system consists of an in situ lens placed approximately 1.5 cm from the
      tunneling region and an ex situ optical lens system to analyze the emitted light,
      for instance, by directing the light into a spectrometer. As a demonstration, we
      measured tip induced photoluminescence spectra of a gold surface. Furthermore, we
      demonstrate that we can simultaneously record scanning tunneling microscope
      induced luminescence and topography of the surface both with atomic resolution.

PMID- 20059148
TI  - Evaluations of pressure-transmitting media for cryogenic experiments with diamond
      anvil cell.
AB  - The fourteen kinds of pressure-transmitting media were evaluated by the ruby
      fluorescence method at room temperature, 77 K using the diamond anvil cell (DAC)
      up to 10 GPa in order to find appropriate media for use in low temperature
      physics. The investigated media are a 1:1 mixture by volume of Fluorinert FC-70
      and FC-77, Daphne 7373 and 7474, NaCl, silicon oil (polydimethylsiloxane),
      Vaseline, 2-propanol, glycerin, a 1:1 mixture by volume of n-pentane and
      isopentane, a 4:1 mixture by volume of methanol and ethanol, petroleum ether,
      nitrogen, argon, and helium. The nonhydrostaticity of the pressure is discussed
      from the viewpoint of the broadening effect of the ruby R(1) fluorescence line.
      The R(1) line basically broadens above the liquid-solid transition pressure at
      room temperature. However, the nonhydrostatic effects do constantly develop in
      all the media from the low-pressure region at low temperature. The relative
      strength of the nonhydrostatic effects in the media at the low temperature region
      is discussed. The broadening effect of the ruby R(1) line in the nitrogen, argon,
      and helium media are significantly small at 77 K, suggesting that the media are
      more appropriate for cryogenic experiments under high pressure up to 10 GPa with
      the DAC. The availability of the three media was also confirmed at 4.2 K.

PMID- 20059149
TI  - Longitudinal detection of ferromagnetic resonance using x-ray transmission
      measurements.
AB  - We describe a setup for the x-ray detection of ferromagnetic resonance in the
      longitudinal geometry using element-specific transmission measurements. Thin
      magnetic film samples are placed in a static magnetic field collinear with the
      propagation direction of a polarized soft x-ray beam and driven to ferromagnetic
      resonance by a continuous wave microwave magnetic field perpendicular to it. The
      transmitted photon flux is measured both as a function of the x-ray photon energy
      and as a function of the applied static magnetic field. We report experiments
      performed on a 15 nm film of doped Permalloy (Ni(73)Fe(18)Gd(7)Co(2)) at the
      L(3)/L(2)-edges of Fe, Co, and Ni. The achieved ferromagnetic resonance
      sensitivity is about 0.1 monolayers/square root(Hz). The obtained results are
      interpreted in the framework of a conductivity tensor based formalism. The
      factors limiting the sensitivity as well as different approaches for the x-ray
      detection of ferromagnetic resonance are discussed.

PMID- 20059150
TI  - A spin-echo resolved grazing incidence scattering setup for the neutron
      interrogation of buried nanostructures.
AB  - We present a dedicated experimental spin-echo resolved grazing incidence
      scattering (SERGIS) setup for the investigation of surfaces and thin films
      exhibiting large lateral length scales. This technique uses the neutron spin to
      encode one in-plane component of the wave-vector transfer in a grazing angle
      scattering experiment. Instead of the scattering angle, the depolarization of the
      scattered beam is measured. This allows one to achieve a very high in-plane
      momentum resolution without collimation of the incident neutron beam in the
      corresponding direction. SERGIS can therefore offer an alternative or
      complementary method to conventional grazing incidence neutron scattering
      experiments. We describe the experimental setup installed at the neutron sources
      ILL (Grenoble) and FRM II (Garching) and present data obtained with this setup on
      various samples exhibiting characteristic mesoscopic length scales in the range
      of several hundred nanometers. We also derive general formulas and error margins
      for the analysis and interpretation of SERGIS data and apply them to the cases of
      a one-dimensional structure and of an island morphology.

PMID- 20059151
TI  - Phase-sensitive terahertz spectroscopy with backward-wave oscillators in
      reflection mode.
AB  - In this article we describe a method which allows accurate measurements of the
      complex reflection coefficient r = absolute value(r) x exp(i phi(R)) of a solid
      at frequencies of 1-50 cm(-1) (30 GHz-1.5 THz). Backward-wave oscillators are
      used as sources for monochromatic coherent radiation tunable in frequency. The
      amplitude of the complex reflection (the reflectivity) is measured in a standard
      way, while the phase shift, introduced by the reflection from the sample surface,
      is measured using a Michelson interferometer. This method is particular useful
      for nontransparent samples, where phase-sensitive transmission measurements are
      not possible. The method requires no Kramers-Kronig transformation in order to
      extract the sample's electrodynamic properties (such as the complex dielectric
      function or complex conductivity). Another area of application of this method is
      the study of magnetic materials with complex dynamic permeabilities different
      from unity at the measurement frequencies (for example, colossal
      magnetoresistance materials and metamaterials). Measuring both the phase
      sensitive transmission and the phase-sensitive reflection allows for a
      straightforward model-independent determination of the dielectric permittivity
      and magnetic permeability of such materials.

PMID- 20059152
TI  - High energy x-ray diffraction/x-ray fluorescence spectroscopy for high-throughput
      analysis of composition spread thin films.
AB  - High-throughput crystallography is an important tool in materials research,
      particularly for the rapid assessment of structure-property relationships. We
      present a technique for simultaneous acquisition of diffraction images and
      fluorescence spectra on a continuous composition spread thin film using a 60 keV
      x-ray source. Subsequent noninteractive data processing provides maps of the
      diffraction profiles, thin film fiber texture, and composition. Even for highly
      textured films, our diffraction technique provides detection of diffraction from
      each family of Bragg reflections, which affords direct comparison of the measured
      profiles with powder patterns of known phases. These techniques are important for
      high throughput combinatorial studies as they provide structure and composition
      maps which may be correlated with performance trends within an inorganic library.

PMID- 20059153
TI  - Combined multiaxial deformation of polymers with in situ small angle and wide
      angle x-ray scattering techniques.
AB  - A unique multiaxial deformation device has been designed and built specifically
      for simultaneous synchrotron small angle x-ray scattering (SAXS) and wide angle x
      ray scattering (WAXS) measurements. The device can operate at strain rates of
      0.0005-0.3 s(-1) and induce strains up to stretch ratios of 5. Measurements can
      either be made at ambient or at elevated temperatures (up to approximately 150
      degrees C), the latter using a heating unit. The capabilities of the device
      coupled with simultaneous SAXS/WAXS measurements have been demonstrated by
      studying the morphological evolution of a number of polymers and their
      nanocomposites.

PMID- 20059154
TI  - Highly sensitive silicon microreactor for catalyst testing.
AB  - A novel microfabricated chemical reactor for highly sensitive measurements of
      catalytic activity and surface kinetics is presented. The reactor is fabricated
      in a silicon chip and is intended for gas-phase reactions at pressures ranging
      from 0.1 to 5.0 bar. A high sensitivity is obtained by directing the entire gas
      flow through the catalyst bed to a mass spectrometer, thus ensuring that nearly
      all reaction products are present in the analyzed gas flow. Although the device
      can be employed for testing a wide range of catalysts, the primary aim of the
      design is to allow characterization of model catalysts which can only be obtained
      in small quantities. Such measurements are of significant fundamental interest
      but are challenging because of the low surface areas involved. The relationship
      between the reaction zone gas flow and the pressure in the reaction zone is
      investigated experimentally. A corresponding theoretical model is presented, and
      the gas flow through an on-chip flow-limiting capillary is predicted to be in the
      intermediate regime. The experimental data for the gas flow are found to be in
      good agreement with the theoretical model. At typical experimental conditions,
      the total gas flow through the reaction zone is around 3x10(14) molecules s(-1),
      corresponding to a gas residence time in the reaction zone of about 11 s. To
      demonstrate the operation of the microreactor, CO oxidation on low-area platinum
      thin film circles is employed as a test reaction. Using temperature ramping, it
      is found that platinum catalysts with areas as small as 15 microm(2) are
      conveniently characterized with the device.

PMID- 20059155
TI  - A more efficient device for preparing model-membrane liposomes by the rapid
      solvent exchange method.
AB  - We modified the original design for a rapid solvent exchange (RSE) device with
      the intent of making the RSE method (i) more efficient and (ii) easier to adopt
      and implement. Our modifications improved solvent-removal kinetics by a factor of
      2, while reducing sample-prep time by a factor of 3. In this paper, we develop
      the kinetic model that informed the device revision and we address several RSE
      parameters that have not yet been discussed in the literature. We also provide
      detailed mechanical drawings and present solvent-removal efficiency data that
      confirm the improved performance of our device.

PMID- 20059156
TI  - A luminescence lifetime assisted ratiometric fluorimeter for biological
      applications.
AB  - In general, the most difficult task in developing devices for fluorescence
      ratiometric sensing is the isolation of signals from overlapping emission
      wavelengths. Wavelength discrimination can be achieved by using monochromators or
      bandpass filters, which often lead to decreased signal intensities. The result is
      a device that is both complex and expensive. Here we present an alternative
      system--a low-cost standalone optical fluorimeter based on luminescence lifetime
      assisted ratiometric sensing (LARS). This paper describes the principle of this
      technique and the overall design of the sensor device. The most significant
      innovation of LARS is the ability to discriminate between two overlapping
      luminescence signals based on differences in their luminescence decay rates.
      Thus, minimal filtering is required and the two signals can be isolated despite
      significant overlap of luminescence spectra. The result is a device that is both
      simple and inexpensive. The electronic circuit employs the lock-in amplification
      technique for the signal processing and the system is controlled by an onboard
      microcontroller. In addition, the system is designed to communicate with external
      devices via Bluetooth.

PMID- 20059157
TI  - Observations of Earth space by self-powered stations in Antarctica.
AB  - Coupling of the solar wind to the Earth magnetosphere/ionosphere is primarily
      through the high latitude regions, and there are distinct advantages in making
      remote sensing observations of these regions with a network of ground-based
      observatories over other techniques. The Antarctic continent is ideally situated
      for such a network, especially for optical studies, because the larger offset
      between geographic and geomagnetic poles in the south enables optical
      observations at a larger range of magnetic latitudes during the winter darkness.
      The greatest challenge for such ground-based observations is the generation of
      power and heat for a sizable ground station that can accommodate an optical
      imaging instrument. Under the sponsorship of the National Science Foundation, we
      have developed suitable automatic observing platforms, the Automatic Geophysical
      Observatories (AGOs) for a network of six autonomous stations on the Antarctic
      plateau. Each station housed a suite of science instruments including a dual
      wavelength intensified all-sky camera that records the auroral activity, an
      imaging riometer, fluxgate and search-coil magnetometers, and ELF/VLF and
      LM/MF/HF receivers. Originally these stations were powered by propane fuelled
      thermoelectric generators with the fuel delivered to the site each Antarctic
      summer. A by-product of this power generation was a large amount of useful heat,
      which was applied to maintain the operating temperature of the electronics in the
      stations. Although a reasonable degree of reliability was achieved with these
      stations, the high cost of the fuel air lift and some remaining technical issues
      necessitated the development of a different type of power unit. In the second
      phase of the project we have developed a power generation system using renewable
      energy that can operate automatically in the Antarctic winter. The most reliable
      power system consists of a type of wind turbine using a simple permanent magnet
      rotor and a new type of power control system with variable resistor shunts to
      regulate the power and dissipate the excess energy and at the same time provide
      heat for a temperature controlled environment for the instrument electronics and
      data system. We deployed such systems and demonstrated a high degree of
      reliability in several years of operation in spite of the relative
      unpredictability of the Antarctic environment. Sample data are shown to
      demonstrate that the AGOs provide key measurements, which would be impossible
      without the special technology developed for this type of observing platform.

PMID- 20059158
TI  - Attofarad resolution potentiostat for electrochemical measurements on nanoscale
      biomolecular interfacial systems.
AB  - We present an instrument that enables electrochemical measurements (cyclic
      voltammetry, impedance tracking, and impedance spectroscopy) on submicrometric
      samples. The system features a frequency range from dc to 1 MHz and a current
      resolution of 10 fA for a measurement time of 1 s, giving a sensitivity of few
      attofarads in terms of measurable capacitance with an applied voltage of only 100
      mV. These performances are obtained using a low-noise wide-bandwidth
      integrator/differentiator stage to sense the input current and a modular approach
      to minimize the effect of input stray capacitances. A digitally implemented lock
      in filter optimally extracts the impedance of the sample, providing time tracking
      and spectroscopy operating modes. This computer-based and flexible instrument is
      well suited for characterizing and tracking the electrical properties of
      biomolecules kept in the physiological solution down to the nanoscale.

PMID- 20059159
TI  - Development of a cryogenic duplexer for solid-state nuclear magnetic resonance.
AB  - To fully appreciate sensitivity enhancement achievable by reducing thermal noise
      at the detection coil for nuclear magnetic resonance (NMR), a duplexer
      operational at low temperature is required. In this work, we developed a
      cryogenic duplexer that can work below 50 K using GaAs diodes and rf
      microelectrical mechanical systems switches. As the observed leakage of a rf
      pulse (100 W and 50 micros) through the duplexer is below 1 mW, it can be used
      not only for NMR in liquids but also for NMR in solids. We reported recently the
      cryocoil magic-angle spinning (MAS) probe [T. Mizuno et al., Rev. Sci. Instrum.
      79, 044706 (2008)] into which was incorporated with this duplexer and a
      commercial rf preamplifier, we show that signal-to-noise ratio gain of 4.0 times
      can be achieved for (1)H MAS-NMR by lowering the detection-coil temperature to 12
      K and the temperatures for the rf preamplifier and the duplexer to 43 K.

PMID- 20059160
TI  - A radio-frequency source using direct digital synthesis and field programmable
      gate array for nuclear magnetic resonance.
AB  - A radio-frequency (rf) source for nuclear magnetic resonance (NMR) is described.
      With the application of direct digital synthesis (DDS), the rf source has the
      ability to yield rf pulses with short switching time and high resolution in
      frequency and phase. To facilitate the generation of a soft pulse, a field
      programmable gate array (FPGA) cooperating with a pulse programmer is used as the
      auxiliary controller of the DDS chip. Triggered by the pulse programmer, the FPGA
      automatically controls the DDS to generate soft pulse according to predefined
      parameters, and the operation mode of the pulse programmer is optimized. The rf
      source is suitable for being used as transmitter in low-field (<1 T) NMR
      applications, for example, magnetic resonance imaging and relaxation measurement.
      As a compact and low-cost module, the rf source is of general use for
      constructing low-field NMR spectrometer.

PMID- 20059161
TI  - Analysis of thermoreflectance signals and characterization of thermal
      conductivity of metal thin films.
AB  - The temperature response of the thermal conductivity (lambda) of metal thin films
      has been investigated by the thermoreflectance (TR) method. The phase lag of the
      TR signals depends on the thermal diffusivity when the heating area is small,
      while on the thermal effusivity when the heating area is large. This enables us
      to evaluate lambda by analyzing the three-dimensional thermal propagation in the
      film on the substrate. We show that by analyzing the TR signals, lambda of Cu-Pt
      alloy thin films formed on glass substrates can be estimated. The estimated
      lambda drastically decreases with an increase in the Pt concentration.
      Furthermore, we discuss these results by considering the crystallographic
      properties of the abovementioned thin films investigated by transmission electron
      microscopy and x-ray diffraction.

PMID- 20059162
TI  - New methodology for simultaneous volumetric and calorimetric measurements: direct
      determination of alpha(p) and C(p) for liquids under pressure.
AB  - A new batch cell has been developed to measure simultaneously both isobaric
      thermal expansion and isobaric heat capacity from calorimetric measurements. The
      isobaric thermal expansion is directly proportional to the linear displacement of
      an inner flexible below and the heat capacity is calculated from the calorimetric
      signal. The apparatus used was a commercial Setaram C-80 calorimeter and together
      with this type of vessels can be operated up to 20 MPa and in the temperature
      range of 303.15-523.15 K, In this work, calibration was carried out using 1
      hexanol and subsequently both thermophysical properties were determined for 3
      pentanol, 3-ethyl-3-pentanol, and 1-octanol at atmospheric pressure, 5 and 10
      MPa, and from 303.15 to 423.15 K in temperature. Finally experimental values were
      compared with the literature in order to validate this new methodology, which
      allows a very accurate determination of isobaric thermal expansion and isobaric
      heat capacity.

PMID- 20059163
TI  - Improvement of energy efficiency via spectrum optimization of excitation sequence
      for multichannel simultaneously triggered airborne sonar system.
AB  - Both the energy efficiency and correlation characteristics are important in
      airborne sonar systems to realize multichannel ultrasonic transducers working
      together. High energy efficiency can increase echo energy and measurement range,
      and sharp autocorrelation and flat cross correlation can help eliminate cross
      talk among multichannel transducers. This paper addresses energy efficiency
      optimization under the premise that cross-talk between different sonar
      transducers can be avoided. The nondominated sorting genetic algorithm-II is
      applied to optimize both the spectrum and correlation characteristics of the
      excitation sequence. The central idea of the spectrum optimization is to
      distribute most of the energy of the excitation sequence within the frequency
      band of the sonar transducer; thus, less energy is filtered out by the
      transducers. Real experiments show that a sonar system consisting of eight
      channel Polaroid 600 series electrostatic transducers excited with 2 ms optimized
      pulse-position-modulation sequences can work together without cross-talk and can
      measure distances up to 650 cm with maximal 1% relative error.

PMID- 20059164
TI  - Transfer-arm evaporator cell for rapid loading and deposition of organic thin
      films.
AB  - Described herein is a transfer-arm evaporator cell (TAE-cell), which allows for
      rapid loading of materials into vacuum for low-temperature sublimation deposition
      of thin films. This design can be incorporated with an existing analysis system
      for convenient in situ thin film characterization. This evaporator is especially
      well suited for photoemission characterization of organic semiconductor
      interfaces. Photoemission is one of the most important techniques for
      characterizing such, however, it generally requires in situ sample preparation.
      The ease with which materials can be loaded and evaporated with this design
      increases the throughput of in situ photoemission characterization, and broadens
      the research scope of the technique. Here, we describe the design, operation, and
      performance of the TAE-cell.

PMID- 20059165
TI  - Direct fabrication of nanopores in a metal foil using focused ion beam with in
      situ measurements of the penetrating ion beam current.
AB  - A through hole with a diameter less than 100 nm was fabricated in an Ag foil
      using only a focused ion beam (FIB) system and in situ measurements of the
      penetrating ion beam. During the drilling of the foil by a FIB of Ga(+) ions, the
      transmitted part of the beam was measured with an electrode mounted on the back
      face of the foil. When the beam current penetrating through the nanopore reached
      a certain value, irradiation was stopped and the area of the created aperture was
      measured with a scanning electron microscope. The resulting area was correlated
      with the current of the penetrating ion beam. This suggests that we can fabricate
      a nanopore of the desired size by controlling the ion beam via penetrating ion
      beam measurements. The smallest aperture thus created was circular with diameter
      of 30 nm.

PMID- 20059166
TI  - A method for atomic force microscopy cantilever stiffness calibration under heavy
      fluid loading.
AB  - This work presents a method for force calibration of rectangular atomic force
      microscopy (AFM) microcantilevers under heavy fluid loading. Theoretical modeling
      of the thermal response of microcantilevers is discussed including a fluid
      structure interaction model of the cantilever-fluid system that incorporates the
      results of the fluctuation-dissipation theorem. This model is curve fit to the
      measured thermal response of a cantilever in de-ionized water and a cost function
      is used to quantify the difference between the theoretical model and measured
      data. The curve fit is performed in a way that restricts the search space to
      parameters that reflect heavy fluid loading conditions. The resulting fitting
      parameters are used to calibrate the cantilever. For comparison, cantilevers are
      calibrated using Sader's method in air and the thermal noise method in both air
      and water. For a set of eight cantilevers ranging in stiffness from 0.050 to 5.8
      N/m, the maximum difference between Sader's calibration performed in air and the
      new method performed in water was 9.4%. A set of three cantilevers that violate
      the aspect ratio assumption associated with the fluid loading model (length-to
      width ratios less than 3.5) ranged in stiffness from 0.85 to 4.7 N/m and yielded
      differences as high as 17.8%.

PMID- 20059167
TI  - Array lead zirconate titanate/glass piezoelectric microcantilevers for real-time
      detection of Bacillus anthracis with 10 spores/ml sensitivity and 1/1000
      selectivity in bacterial mixtures.
AB  - An array of three identical piezoelectric microcantilever sensors (PEMSs)
      consisting of a lead zirconate titanate layer bonded to a glass layer was
      fabricated and examined for simultaneous, in situ, real-time, all-electrical
      detection of Bacillus anthracis (BA) spores in an aqueous suspension using the
      first longitudinal extension mode of resonance. With anti-BA antibody immobilized
      on the sensor surfaces all three PEMS exhibited identical BA detection resonance
      frequency shifts at all tested concentrations, 10-10(7) spores/ml with a standard
      deviation of less than 10%. The detection concentration limit of 10 spores/ml was
      about two orders of magnitude lower than would be permitted by flexural peaks. In
      blinded-sample testing, the array PEMS detected BA in three samples containing
      BA: (1) 3.3x10(3) spores/ml, (2) a mixture of 3.3x10(3) spores/ml and 3.3x10(5)
      S. aureus (SA) and P. aeruginosa (PA) per ml, and (3) a mixture of 3.3x10(3)
      spores/ml with 3.3x10(6) SA+PA/ml. There was no response to a sample containing
      only 3.3x10(6) SA+PA/ml. These results illustrate the sensitivity, specificity,
      reusability, and reliability of array PEMS for in situ, real-time detection of BA
      spores.

PMID- 20059169
TI  - Inner-shell photoionization spectroscopy on deposited metal clusters using soft x
      ray synchrotron radiation: an experimental setup.
AB  - Exploration of mass-selected clusters by soft x-ray synchrotron radiation is well
      suited to receive element specific information on clusters in contact with a
      support and to systematically follow the evolution of size-dependent electronic
      and geometrical properties from the smallest clusters toward the bulk. Here we
      describe an experimental setup, which combines cluster synthesis, mass selection,
      soft landing, ultrahigh vacuum transfer, and photoionization experiments such as
      x-ray photoelectron spectroscopy, x-ray absorption, and Auger electron
      spectroscopy. First spectroscopic results and experimental conditions are briefly
      discussed for Cu(19) deposited onto the natural oxide layer of a Si-wafer
      surface.

PMID- 20059168
TI  - A combined nanoplasmonic and electrodeless quartz crystal microbalance setup.
AB  - We have developed an instrument combining localized surface plasmon resonance
      (LSPR) sensing with electrodeless quartz crystal microbalance with dissipation
      monitoring (QCM-D). The two techniques can be run simultaneously, on the same
      sensor surface, and with the same time resolution and sensitivity as for the
      individual techniques. The electrodeless QCM eliminates the need to fabricate
      electrodes on the quartz crystal and gives a large flexibility in choosing the
      surface structure and coating for both QCM-D and LSPR. The performance is
      demonstrated for liquid phase measurements of lipid bilayer formation and
      biorecognition events, and for gas phase measurements of hydrogen uptake/release
      by palladium nanoparticles. Advantages of using the combined equipment for
      biomolecular adsorption studies include synchronized information about structural
      transformations and extraction of molecular (dry) mass and degree of hydration of
      the adlayer, which cannot be obtained with the individual techniques. In hydrogen
      storage studies the combined equipment, allows for synchronized measurements of
      uptake/release kinetics and quantification of stored hydrogen amounts in
      nanoparticles and films at practically interesting hydrogen pressures and
      temperatures.

PMID- 20059170
TI  - A new photoelectrochemical test cell and its use for a combined two-electrode and
      three-electrode approach to cell testing.
AB  - This paper describes the design, assembly, and operation of a
      photoelectrochemical (PEC) test cell that is relatively easy to construct and
      well suited for testing photoelectrode/counterelectrode combinations in a
      reproducible manner. The design of the cell permits measurements to be made in
      both two-electrode and three-electrode arrangements. The benefits of conducting
      both two-electrode and three-electrode measurements are illustrated using data
      obtained from the new test cell for a PEC system based on a polysulfide
      electrolyte, CdSe(0.8)Te(0.2) photoanode, and tungsten monocarbide
      counterelectrode. It is shown that linear sweep voltammograms measured in three
      electrode mode can be used to describe current transients recorded in a two
      electrode cell modified by the addition of a reference electrode.

PMID- 20059171
TI  - Improved fiber optic device for in situ determination of electrolyte
      stratification in lead-acid batteries.
AB  - A three-channel, highly sensitive, fiber optic device is presented to measure
      acid concentration in lead-acid batteries during their operation. The refractive
      index and thereby the concentration of sulfuric acid is measured by a bent,
      silica glass fiber tip, stripped off its cladding. Sensor heads of the device are
      small enough to be inserted at different positions in the cell of an ordinary,
      flooded lead-acid battery. Measuring the concentration of the electrolyte at
      different depths of the battery cell, acid stratification can be accurately
      determined. During the test of the instrument, about 0.3 Hz temporal and 0.05 wt
      % concentration resolutions were achieved while the temperature drift was found
      to be -0.25 wt %/degrees C.

PMID- 20059172
TI  - Analysis of the energetic parameters of a theta pinch.
AB  - This work is devoted to study experimentally the performance of a theta pinch
      when the number of capacitors and turns of magnetic coil and the diameter of the
      glass tube are changed. To model the theta pinch a simple RLC circuit is used and
      the measurement of energy transmission from the bank of capacitors to the plasma
      is made using few experimental resources. In this work it was analyzed more than
      2500 curves with a nonlinear procedure. Our results show that it is possible to
      design an optimized theta pinch making the appropriated choice of energetic
      parameters and therefore to reduce the stress of the system.

PMID- 20059173
TI  - A method to evaluate the three-dimensional roughness of fracture surfaces in
      brittle geomaterials.
AB  - Conventionally, the evaluation of fracture surface roughness in brittle
      geomaterials, such as concrete and rock, has been based on the measurement and
      analysis of two-dimensional profiles rather than three-dimensional (3D) surfaces.
      The primary reason for doing so was the lack of tools capable of making 3D
      measurements. However, in recent years, several optical and mechanical
      measurement tools have become available, which are capable of quickly and
      accurately producing high resolution point clouds defining 3D surfaces. This
      paper provides a methodology for evaluating the surface roughness and roughness
      anisotropy using these 3D surface measurements. The methodology is presented step
      by-step to allow others to easily adopt and implement the process to analyze
      their own surface measurement data. The methodology is demonstrated by digitizing
      a series of concrete fracture surfaces and comparing the estimated 3D roughness
      parameters with qualitative observations and estimates of the well-known
      roughness coefficient, R(s).

PMID- 20059174
TI  - Measurement of specimen dimensions and dynamic pressure in dynamic triaxial
      experiments.
AB  - Novel experimental techniques are developed to measure the rapid changes in
      specimen dimensions during dynamic triaxial experiments. A capacitance gage is
      designed and constructed to measure the diameter change of the specimen inside
      the pressure chamber at both low and high rates. The length change is determined
      by a linear variable differential transformer at low rates and by Kolsky bar
      signals at high rates. The Kolsky bar also measures the dynamic axial stress in
      the specimen during the high-rate phase of an experiment. A line pressure gage
      records the hydrostatic pressure in the chamber. The dynamic pressure variation
      in the chamber during axial impact loading is detected by a manganin gage placed
      inside the chamber. The feasibility of this new experimental setup is
      demonstrated by dynamic triaxial experiments on a fine dry sand.

PMID- 20059175
TI  - Maskless optical microscope lithography system.
AB  - A simple maskless photolithography system employing an optical microscope, a
      motorized stage and a beam blanker is proposed. Based on a pattern design, the
      motorized stage shifts a resist-coated substrate exposed by a focused beam under
      a microscope. Microscale patterns are easily defined on a single nanowire without
      using a mask validating the application applying to the research requiring
      frequent changes or free-style designs in microscale test patterns.

PMID- 20059176
TI  - Cleaning of diamond nanoindentation probes with oxygen plasma and carbon dioxide
      snow.
AB  - Diamond nanoindentation probes may perform thousands of indentations over years
      of service life. There is a broad agreement that the probes need frequent
      cleaning, but techniques for doing so are mostly anecdotes shared between
      experimentalists. In preparation for the measurement of the shape of a
      nanoindentation probe by a scanning probe microscope, cleaning by carbon dioxide
      snow jets and oxygen plasma was investigated. Repeated indentation on a
      thumbprint-contaminated surface formed a compound that was very resistant to
      removal by solvents, CO(2) snow, and plasma. CO(2) snow cleaning is found to be a
      generally effective cleaning procedure.

PMID- 20059177
TI  - Current integration force and displacement self-sensing method for cantilevered
      piezoelectric actuators.
AB  - This paper presents a new method of self-sensing both of the displacement and the
      external applied force at the tip of piezoelectric cantilevers. Integrated
      electric current across piezoelectric actuators is compensated against material
      nonlinearities (creep, hysteresis) to provide reliable information. We propose to
      compensate the hysteresis by using the Prandtl-Ishlinskii static approach while
      an auto regressive and moving average exogenous (ARMAX) model is used to minimize
      the creep influence. The quasistatic estimation, electronic circuit, and aspects
      related to long-term charge preservations are described or referenced. As an
      experiment, we tested the actuator entering in contact with a fixed force sensor.
      An input signal of 20 V peak-to-peak (10% of maximum range) led to force self
      sensing errors inferior to +/-8%. A final discussion about method accuracy and
      its limitations is made.

PMID- 20059178
TI  - A new soft x-ray pulse height analysis array in the HL-2A tokamak.
AB  - A new soft x-ray pulse height analysis (PHA) array including nine independent
      subsystems, on basis of a nonconventional software multichannel analysis system
      and a silicon drift detector (SDD) linear array consisting of nine high
      performance SDD detectors, has been developed in the HL-2A tokamak. The use of
      SDD has greatly improved the measurement accuracy and the spatiotemporal
      resolutions of the soft x-ray PHA system. Since the ratio of peak to background
      counts obtained from the SDD PHA system is very high, p/b > or = 3000, the soft x
      ray spectra measured by the SDD PHA system can approximatively be regarded as
      electron velocity distribution. The electron velocity distribution can be well
      derived in the pure ohmic and auxiliary heating discharges. The performance of
      the new soft x-ray PHA array and the first experimental results with some
      discussions are presented.

PMID- 20059179
TI  - Deposition of transparent, conductive tin oxide films on glass using a radio
      frequency induction heater.
AB  - Tin oxide films are often used as transparent, conductive coatings on glass in
      the scientific research setting. The standard approach of depositing these films
      in an oven leads to poor visibility of the substrate and thus inhibits the ready
      formation of uniform, low resistivity films. In this note we describe a simple
      tin oxide film deposition technique using a radio-frequency induction heater that
      allows for in situ visualization of the deposition process and resulting film.
      Uniform films having resistivities as low as 2 mohm cm with transmittances of
      approximately 85% in the visible light spectrum were readily deposited.

PMID- 20059180
TI  - Improved spatial resolution for reflection mode infrared microscopy.
AB  - Standard commercial infrared microscopes operating in reflection mode use a
      mirror to direct the reflected light from the sample to the detector. This mirror
      blocks about half of the incident light, however, and thus degrades the spatial
      resolution by reducing the numerical aperture of the objective. Here, we replace
      the mirror with a 50% beamsplitter to allow full illumination of the objective
      and retain a way to direct the reflected light to the detector. The improved
      spatial resolution is demonstrated using two different microscopes capable of
      diffraction-limited resolution: the first microscope is coupled to a synchrotron
      source and utilizes a single point detector, whereas the second microscope has a
      standard blackbody source and uses a focal plane array detector.

PMID- 20059181
TI  - A versatile thermoelectric temperature controller with 10 mK reproducibility and
      100 mK absolute accuracy.
AB  - We describe a general-purpose thermoelectric temperature controller with 1 mK
      stability, 10 mK reproducibility, and 100 mK absolute accuracy near room
      temperature. The controller design is relatively simple and could be readily
      modified for use in different experimental circumstances. We also describe a time
      domain numerical model that allows one to characterize the stability and
      transient behavior of the system being controlled, even in the presence of
      elements with highly nonlinear responses.

PMID- 20059182
TI  - A new dynamic device for low-dimensional materials testing.
AB  - As the geometrical size of low-dimensional materials decreases to micro- or
      nanoscale, the traditional dynamic loading system cannot be used anymore to
      measure the dynamic mechanical property. In this study, a new dynamic loading
      system was developed. A piezoelectric transducer actuator was used for
      displacement loading, and a mechanical lever was designed to amplify the
      displacement load. Finite element method simulation and validation experiments
      were conducted to analyze the strength and function of the mechanical lever. As
      an application test, a sample from an aluminum film was investigated using the
      system. The success of the experiment, as shown by the results, demonstrated the
      feasibility of the system for low-dimensional materials study.

PMID- 20059183
TI  - Uncertainty of a hybrid surface temperature sensor for silicon wafers and
      comparison with an embedded thermocouple.
AB  - We have developed a user-friendly hybrid surface temperature sensor. The
      uncertainties of temperature readings associated with this sensor and a
      thermocouple embedded in a silicon wafer are compared. The expanded uncertainties
      (k=2) of the hybrid temperature sensor and the embedded thermocouple are 2.11 and
      2.37 K, respectively, in the temperature range between 600 and 1000 K. In the
      present paper, the uncertainty evaluation and the sources of uncertainty are
      described.

PMID- 20059185
TI  - Introduction: Sixth Annual Gallery of Nonlinear Images (Pittsburgh, Pennsylvania,
      2009).

PMID- 20059186
TI  - Superlattice patterns in forced thermal convection.

PMID- 20059187
TI  - Rupture and clustering in granular streams.

PMID- 20059188
TI  - Visualization of communities in networks.

PMID- 20059189
TI  - The mayonnaise droplet.

PMID- 20059190
TI  - Unstable Kolmogorov flow in granular matter.

PMID- 20059191
TI  - Force network ensemble for the triangular lattice: a tale of tiles.

PMID- 20059192
TI  - Generating ensembles of two-dimensional granular configurations.

PMID- 20059193
TI  - X-ray computerized tomography scan of crumpled aluminum sheet.

PMID- 20059194
TI  - The adventures of Dicty, the Dictyostelium cell.

PMID- 20059195
TI  - VORO++: a three-dimensional voronoi cell library in C++.

PMID- 20059196
TI  - Homogenous dislocation nucleation.

PMID- 20059197
TI  - Discrete instability in the DNA double helix.
AB  - Modulational instability (MI) is explored in the framework of the base-rotor
      model of DNA dynamics. We show, in fact, that the helicoidal coupling introduced
      in the spin model of DNA reduces the system to a modified discrete sine-Gordon
      (sG) equation. The MI criterion is thus modified and displays interesting
      features because of the helicoidal coupling. In the simulations, we have found
      that a train of pulses is generated when the lattice is subjected to MI, in
      agreement with analytical results obtained in a modified discrete sG equation.
      Also, the competitive effects of the harmonic longitudinal and helicoidal
      constants on the dynamics of the system are notably pointed out. In the same way,
      it is shown that MI can lead to energy localization which becomes high for some
      values of the helicoidal coupling constant.

PMID- 20059198
TI  - Chaos and crises in a model for cooperative hunting: a symbolic dynamics
      approach.
AB  - In this work we investigate the population dynamics of cooperative hunting
      extending the McCann and Yodzis model for a three-species food chain system with
      a predator, a prey, and a resource species. The new model considers that a given
      fraction sigma of predators cooperates in prey's hunting, while the rest of the
      population 1-sigma hunts without cooperation. We use the theory of symbolic
      dynamics to study the topological entropy and the parameter space ordering of the
      kneading sequences associated with one-dimensional maps that reproduce
      significant aspects of the dynamics of the species under several degrees of
      cooperative hunting. Our model also allows us to investigate the so-called
      deterministic extinction via chaotic crisis and transient chaos in the framework
      of cooperative hunting. The symbolic sequences allow us to identify a critical
      boundary in the parameter spaces (K,C(0)) and (K,sigma) which separates two
      scenarios: (i) all-species coexistence and (ii) predator's extinction via chaotic
      crisis. We show that the crisis value of the carrying capacity K(c) decreases at
      increasing sigma, indicating that predator's populations with high degree of
      cooperative hunting are more sensitive to the chaotic crises. We also show that
      the control method of Dhamala and Lai [Phys. Rev. E 59, 1646 (1999)] can sustain
      the chaotic behavior after the crisis for systems with cooperative hunting. We
      finally analyze and quantify the inner structure of the target regions obtained
      with this control method for wider parameter values beyond the crisis, showing a
      power law dependence of the extinction transients on such critical parameters.

PMID- 20059199
TI  - Permutations and time series analysis.
AB  - The main aim of this paper is to show how the use of permutations can be useful
      in the study of time series analysis. In particular, we introduce a test for
      checking the independence of a time series which is based on the number of
      admissible permutations on it. The main improvement in our tests is that we are
      able to give a theoretical distribution for independent time series.

PMID- 20059200
TI  - Identical phase oscillators with global sinusoidal coupling evolve by Mobius
      group action.
AB  - Systems of N identical phase oscillators with global sinusoidal coupling are
      known to display low-dimensional dynamics. Although this phenomenon was first
      observed about 20 years ago, its underlying cause has remained a puzzle. Here we
      expose the structure working behind the scenes of these systems by proving that
      the governing equations are generated by the action of the Mobius group, a three
      parameter subgroup of fractional linear transformations that map the unit disk to
      itself. When there are no auxiliary state variables, the group action partitions
      the N-dimensional state space into three-dimensional invariant manifolds (the
      group orbits). The N-3 constants of motion associated with this foliation are the
      N-3 functionally independent cross ratios of the oscillator phases. No further
      reduction is possible, in general; numerical experiments on models of Josephson
      junction arrays suggest that the invariant manifolds often contain three
      dimensional regions of neutrally stable chaos.

PMID- 20059201
TI  - Two routes to the one-dimensional discrete nonpolynomial Schrodinger equation.
AB  - The Bose-Einstein condensate (BEC), confined in a combination of the cigar-shaped
      trap and axial optical lattice, is studied in the framework of two models
      described by two versions of the one-dimensional (1D) discrete nonpolynomial
      Schrodinger equation (NPSE). Both models are derived from the three-dimensional
      Gross-Pitaevskii equation (3D GPE). To produce "model 1" (which was derived in
      recent works), the 3D GPE is first reduced to the 1D continual NPSE, which is
      subsequently discretized. "Model 2," which was not considered before, is derived
      by first discretizing the 3D GPE, which is followed by the reduction in the
      dimension. The two models seem very different; in particular, model 1 is
      represented by a single discrete equation for the 1D wave function, while model 2
      includes an additional equation for the transverse width. Nevertheless, numerical
      analyses show similar behaviors of fundamental unstaggered solitons in both
      systems, as concerns their existence region and stability limits. Both models
      admit the collapse of the localized modes, reproducing the fundamental property
      of the self-attractive BEC confined in tight traps. Thus, we conclude that the
      fundamental properties of discrete solitons predicted for the strongly trapped
      self-attracting BEC are reliable, as the two distinct models produce them in a
      nearly identical form. However, a difference between the models is found too, as
      strongly pinned (very narrow) discrete solitons, which were previously found in
      model 1, are not generated by model 2-in fact, in agreement with the continual 1D
      NPSE, which does not have such solutions either. In that respect, the newly
      derived model provides for a more accurate approximation for the trapped BEC.

PMID- 20059202
TI  - The compass rose pattern in electricity prices.
AB  - The "compass rose pattern" is known to appear in the phase portraits, or scatter
      diagrams, of the high-frequency returns of financial series. We first show that
      this pattern is also present in the returns of spot electricity prices. Early
      researchers investigating these phenomena hoped that these patterns signaled the
      presence of rich dynamics, possibly chaotic or fractal in nature. Although there
      is a definite autoregressive and conditional heteroscedasticity structure in
      electricity returns, we find that after simple filtering no pattern remains.
      While the series is non-normal in terms of their distribution and statistical
      tests fail to identify significant chaos, there is evidence of fractal structures
      in periodic price returns when measured over the trading day. The phase diagram
      of the filtered returns provides a useful visual check on independence, a
      property necessary for pricing and trading derivatives and portfolio
      construction, as well as providing useful insights into the market dynamics.

PMID- 20059203
TI  - The impact of risk-averse operation on the likelihood of extreme events in a
      simple model of infrastructure.
AB  - A simple dynamic model of agent operation of an infrastructure system is
      presented. This system evolves over a long time scale by a daily increase in
      consumer demand that raises the overall load on the system and an engineering
      response to failures that involves upgrading of the components. The system is
      controlled by adjusting the upgrading rate of the components and the replacement
      time of the components. Two agents operate the system. Their behavior is
      characterized by their risk-averse and risk-taking attitudes while operating the
      system, their response to large events, and the effect of learning time on
      adapting to new conditions. A risk-averse operation causes a reduction in the
      frequency of failures and in the number of failures per unit time. However, risk
      aversion brings an increase in the probability of extreme events.

PMID- 20059204
TI  - Transport properties in nontwist area-preserving maps.
AB  - Nontwist systems, common in the dynamical descriptions of fluids and plasmas,
      possess a shearless curve with a concomitant transport barrier that eliminates or
      reduces chaotic transport, even after its breakdown. In order to investigate the
      transport properties of nontwist systems, we analyze the barrier escape time and
      barrier transmissivity for the standard nontwist map, a paradigm of such systems.
      We interpret the sensitive dependence of these quantities upon map parameters by
      investigating chaotic orbit stickiness and the associated role played by the
      dominant crossing of stable and unstable manifolds.

PMID- 20059205
TI  - Fixed points, stable manifolds, weather regimes, and their predictability.
AB  - In a simple, one-layer atmospheric model, we study the links between low
      frequency variability and the model's fixed points in phase space. The model
      dynamics is characterized by the coexistence of multiple "weather regimes." To
      investigate the transitions from one regime to another, we focus on the
      identification of stable manifolds associated with fixed points. We show that
      these manifolds act as separatrices between regimes. We track each manifold by
      making use of two local predictability measures arising from the meteorological
      applications of nonlinear dynamics, namely, "bred vectors" and singular vectors.
      These results are then verified in the framework of ensemble forecasts issued
      from "clouds" (ensembles) of initial states. The divergence of the trajectories
      allows us to establish the connections between zones of low predictability, the
      geometry of the stable manifolds, and transitions between regimes.

PMID- 20059206
TI  - Accurate noise projection for reduced stochastic epidemic models.
AB  - We consider a stochastic susceptible-exposed-infected-recovered (SEIR)
      epidemiological model. Through the use of a normal form coordinate transform, we
      are able to analytically derive the stochastic center manifold along with the
      associated, reduced set of stochastic evolution equations. The transformation
      correctly projects both the dynamics and the noise onto the center manifold.
      Therefore, the solution of this reduced stochastic dynamical system yields
      excellent agreement, both in amplitude and phase, with the solution of the
      original stochastic system for a temporal scale that is orders of magnitude
      longer than the typical relaxation time. This new method allows for improved time
      series prediction of the number of infectious cases when modeling the spread of
      disease in a population. Numerical solutions of the fluctuations of the SEIR
      model are considered in the infinite population limit using a Langevin equation
      approach, as well as in a finite population simulated as a Markov process.

PMID- 20059207
TI  - Bifurcation and chaos in spin-valve pillars in a periodic applied magnetic field.
AB  - We study the bifurcation and chaos scenario of the macromagnetization vector in a
      homogeneous nanoscale-ferromagnetic thin film of the type used in spin-valve
      pillars. The underlying dynamics is described by a generalized Landau-Lifshitz
      Gilbert (LLG) equation. The LLG equation has an especially appealing form under a
      complex stereographic projection, wherein the qualitative equivalence of an
      applied field and a spin-current induced torque is transparent. Recently, chaotic
      behavior of such a spin vector has been identified by Li et al. [ Phys. Rev. B
      74, 054417 (2006)] using a spin-polarized current passing through the pillar of
      constant polarization direction and periodically varying magnitude, owing to the
      spin-transfer torque effect. In this paper, we show that the same dynamical
      behavior can be achieved using a periodically varying applied magnetic field in
      the presence of a constant dc magnetic field and constant spin current, which is
      technically much more feasible, and demonstrate numerically the chaotic dynamics
      in the system for an infinitely thin film. Further, it is noted that in the
      presence of a nonzero crystal anisotropy field, chaotic dynamics occurs at much
      lower magnitudes of the spin current and dc applied field.

PMID- 20059208
TI  - Chaoticity of the blood cell production system.
AB  - We present a structured model of stem cells given by a partial differential
      equation. This equation generates a semiflow acting on the set of densities. We
      show that this semiflow possesses an invariant exact measure positive on open
      sets. From this it follows that the system is chaotic, i.e., it has dense
      trajectories and each trajectory is unstable.

PMID- 20059209
TI  - Synchronization in coupled time-delayed systems with parameter mismatch and noise
      perturbation.
AB  - In this paper, a design of coupling and effective sufficient condition for stable
      complete synchronization and antisynchronization of a class of coupled time
      delayed systems with parameter mismatch and noise perturbation are established.
      Based on the LaSalle-type invariance principle for stochastic differential
      equations, sufficient conditions guaranteeing complete synchronization and
      antisynchronization with constant time delay are developed. Also delay-dependent
      sufficient conditions for the case of time-varying delay are derived by using the
      Lyapunov approach for stochastic differential equations. Numerical examples fully
      support the analytical results.

PMID- 20059210
TI  - Unpinning of a spiral wave anchored around a circular obstacle by an external
      wave train: common aspects of a chemical reaction and cardiomyocyte tissue.
AB  - It is well known that spiral waves are often stabilized by anchoring to a local
      heterogeneity ("pinning") and that such pinned waves are rather difficult to
      eliminate. In the present report, we show that pinned spiral waves can be
      eliminated through collision with a wave train arriving from the outer region, as
      confirmed in experiments on the Belousov-Zhabotinsky (BZ) reaction as well as in
      cardiomyocyte tissue culture. A numerical simulation using the Oregonator, a
      mathematical model for the BZ reaction, provides the parameter area for
      successful unpinning. The scenario of unpinning is discussed in terms of the
      dispersion relation of the wave train by taking into account the curvature effect
      of the excitation wave.

PMID- 20059211
TI  - Dynamical estimates of chaotic systems from Poincare recurrences.
AB  - We show a function that fits well the probability density of return times between
      two consecutive visits of a chaotic trajectory to finite size regions in phase
      space. It deviates from the exponential statistics by a small power-law term, a
      term that represents the deterministic manifestation of the dynamics. We also
      show how one can quickly and easily estimate the Kolmogorov-Sinai entropy and the
      short-term correlation function by realizing observations of high probable
      returns. Our analyses are performed numerically in the Henon map and
      experimentally in a Chua's circuit. Finally, we discuss how our approach can be
      used to treat the data coming from experimental complex systems and for
      technological applications.

PMID- 20059212
TI  - Three-dimensional patterns in the Lengyel-Rabai-Epstein model of the chlorine
      dioxide-iodine-malonic acid reaction.
AB  - We present computational solutions to the Lengyel-Rabai-Epstein model in three
      space dimensions. The results show that three-dimensional patterns exist and that
      they differ significantly from the two-dimensional patterns. Patterns occur at
      three locations in the reactor corresponding to peaks in the one-dimensional
      concentration of the starch tri-iodide concentration. Each pattern possesses its
      own intrinsic wavelength and is neither striped nor hexagonal, the two types that
      have been shown to exist in two dimensions. Computations suggest a bifurcation
      exists as a function of the reactor thickness. Solutions are computed using a
      high-order adaptive finite element method coupled with a multistep integrator in
      time. Linear systems generated in the multistep solver are solved using the
      iterative method GMRES with a Jacobi preconditioner. Matrix storage is reduced by
      incomplete assembly via thresholding. Preconditioner factorization and matrix
      vector multiplication efficiency are enhanced by the use of OPENMP.

PMID- 20059213
TI  - Time-shifted synchronization of chaotic oscillator chains without explicit
      coupling delays.
AB  - We examine chains of unidirectionally coupled oscillators in which time-shifted
      synchronization occurs without explicit delays in the coupling. In numerical
      simulations and in an experimental system of electronic oscillators, we examine
      the time shift and the degree of distortion (primarily in the form of
      attenuation) of the waveforms of the oscillators located far from the drive
      oscillator. Surprisingly, under weak coupling we observe minimal attenuation in
      spite of a significant total time shift. In contrast, at higher coupling
      strengths the observed attenuation increases dramatically and approaches the
      value predicted by an analytically derived estimate. In this regime, we verify
      directly that generalized synchronization is maintained over the entire chain
      length despite severe attenuation. These results suggest that weak coupling
      generally may produce higher quality synchronization in systems for which truly
      identical synchronization is not possible.

PMID- 20059214
TI  - Error distribution in randomly perturbed orbits.
AB  - Given an observable f defined on the phase space of some dynamical system
      generated by the mapT, we consider the error between the value of the function
      f(Tnx0) computed at time n along the orbit with initial condition x0, and the
      value f(Tn x0) of the same observable computed by replacing the map Tn with the
      composition of maps T(omega)(n)o...oT(omega)1, where each T(omega) is chosen
      randomly, by varying omega, in a neighborhood of size of T. We show that the
      random variable Delta(n)omega [triple bond] f(Tnx0) -f(T(omega)nx0), depending on
      the initial condition x0 and on the choice of the realization omega, will
      converge in distribution when n-->infinity to what we call the asymptotic error.
      We study in detail the density of the distribution function of the asymptotic
      error for a wide class of dynamical systems perturbed with additive noise: for a
      few of them we give rigorous results, for the others we provide a numerical
      investigation. Our study is intended as a model for the effects of numerical
      noise due to roundoff on dynamical systems.

PMID- 20059215
TI  - Generalized synchronization of complex dynamical networks via impulsive control.
AB  - This paper investigates the generalized synchronization (GS) of two typical
      complex dynamical networks, small-world networks and scale-free networks, in
      terms of impulsive control strategy. By applying the auxiliary-system approach to
      networks, we demonstrate theoretically that for any given coupling strength, GS
      can take place in complex dynamical networks consisting of nonidentical systems.
      Particularly, for Barabasi-Albert scale-free networks, we look into the relations
      between GS error and topological parameter m, which denotes the number of edges
      linking to a new node at each time step, and find out that GS speeds up with
      increasing m. And for Newman-Watts small-world networks, the time needed to
      achieve GS decreases as the probability of adding random edges increases. We
      further reveal how node dynamics affects GS speed on both small-world and scale
      free networks. Finally, we analyze how the development of GS depends on impulsive
      control gains. Some abnormal but interesting phenomena regarding the GS process
      are also found in simulations.

PMID- 20059216
TI  - Synchronization and chaotic dynamics of coupled mechanical metronomes.
AB  - Synchronization scenarios of coupled mechanical metronomes are studied by means
      of numerical simulations showing the onset of synchronization for two, three, and
      100 globally coupled metronomes in terms of Arnol'd tongues in parameter space
      and a Kuramoto transition as a function of coupling strength. Furthermore, we
      study the dynamics of metronomes where overturning is possible. In this case
      hyperchaotic dynamics associated with some diffusion process in configuration
      space is observed, indicating the potential complexity of metronome dynamics.

PMID- 20059217
TI  - Mixed-mode oscillations and chaos in a prey-predator system with dormancy of
      predators.
AB  - It is shown that the dormancy of predators induces mixed-mode oscillations and
      chaos in the population dynamics of a prey-predator system under certain
      conditions. The mixed-mode oscillations and chaos are shown to bifurcate from a
      coexisting equilibrium by means of the theory of fast-slow systems. These results
      may help to find experimental conditions under which one can demonstrate chaotic
      population dynamics in a simple phytoplankton-zooplankton (-resting eggs)
      community in a microcosm with a short duration.

PMID- 20059218
TI  - Rank one chaos in a class of planar systems with heteroclinic cycle.
AB  - In this paper, we study rank one chaos in a class of planar systems with
      heteroclinic cycle. We first find a stable limit cycle inside the heteroclinic
      cycle. We then add an external periodic forcing to create rank one chaos. We
      follow a step-by-step procedure guided by the theory of rank one chaos to find
      experimental evidence of strange attractors with Sinai, Ruelle, and Bowen
      measures.

PMID- 20059219
TI  - Epidemics with multistrain interactions: the interplay between cross immunity and
      antibody-dependent enhancement.
AB  - This paper examines the interplay of the effect of cross immunity and antibody
      dependent enhancement (ADE) in multistrain diseases. Motivated by dengue fever,
      we study a model for the spreading of epidemics in a population with multistrain
      interactions mediated by both partial temporary cross immunity and ADE. Although
      ADE models have previously been observed to cause chaotic outbreaks, we show
      analytically that weak cross immunity has a stabilizing effect on the system.
      That is, the onset of disease fluctuations requires a larger value of ADE with
      small cross immunity than without. However, strong cross immunity is shown
      numerically to cause oscillations and chaotic outbreaks even for low values of
      ADE.

PMID- 20059220
TI  - Investigation of both local and global topological ingredients on transport
      efficiency in scale-free networks.
AB  - This paper investigates the combined effect of local and global topological
      ingredients for routing packets on transport efficiency in scale-free networks
      with different degree exponents. Four different transport efficiency
      measurements, namely, the critical packet generation rate, the average number of
      overall packet loads, the relative variance of packet number on each node, and
      the relative variance of transport time from source to destination, are
      investigated in this paper. The combined effects of global and local ingredients
      on four measurements are presented and analyzed. We also investigate the effect
      of degree exponent on four measurements. Based on the results we obtained, we
      propose an improved routing strategy with memory information. Simulation results
      show that the critical packet generation rate can be efficiently improved by
      using the improved routing strategy with memory information, especially when
      packets are showing strong inclination of being forwarded to low-degree or high
      degree nodes in scale-free networks with small degree exponents.

PMID- 20059221
TI  - Front waves and complex spatiotemporal patterns in a reaction-diffusion
      convection system with thermokinetic autocatalysis.
AB  - We analyze dynamics of stationary nonuniform patterns, traveling waves, and
      spatiotemporal chaos in a simple model of a tubular cross-flow reactor. The
      reactant is supplied continuously via convective flow and/or by diffusion through
      permeable walls of the reactor. First order exothermic reaction kinetics is
      assumed and the system is described by mass and energy balances forming coupled
      reaction-diffusion-convection equations. Dynamical regimes of the reaction
      diffusion subsystem range from pulses and fronts to periodic waves and complex
      chaotic behavior. Two distinct types of chaotic patterns are identified and
      characterized by Lyapunov dimension. Next we examine the effects of convection on
      various types of the reaction-diffusion regimes. Remarkable zigzag fronts and
      steady state patterns are found despite the absence of differential flow. We
      employ continuation techniques to elucidate the existence and form of these
      patterns.

PMID- 20059222
TI  - Control of spatiotemporal patterns in the Gray-Scott model.
AB  - This paper studies the effects of a time-delayed feedback control on the
      appearance and development of spatiotemporal patterns in a reaction-diffusion
      system. Different types of control schemes are investigated, including single
      species, diagonal, and mixed control. This approach helps to unveil different
      dynamical regimes, which arise from chaotic state or from traveling waves. In the
      case of spatiotemporal chaos, the control can either stabilize uniform steady
      states or lead to bistability between a trivial steady state and a propagating
      traveling wave. Furthermore, when the basic state is a stable traveling pulse,
      the control is able to advance stationary Turing patterns or yield the above
      mentioned bistability regime. In each case, the stability boundary is found in
      the parameter space of the control strength and the time delay, and numerical
      simulations suggest that diagonal control fails to control the spatiotemporal
      chaos.

PMID- 20059223
TI  - Robust extremes in chaotic deterministic systems.
AB  - This paper introduces the notion of robust extremes in deterministic chaotic
      systems, presents initial theoretical results, and outlines associated
      inferential techniques. A chaotic deterministic system is said to exhibit robust
      extremes under a given observable when the associated statistics of extreme
      values depend smoothly on the system's control parameters. Robust extremes are
      here illustrated numerically for the flow of the Lorenz model [E. N. Lorenz, J.
      Atmos. Sci. 20, 130 (1963)]. Robustness of extremes is proved for one-dimensional
      Lorenz maps with two distinct types of observables for which conditions
      guaranteeing robust extremes are formulated explicitly. Two applications are
      shown: improving the precision of the statistical estimator for extreme value
      distributions and predicting future extremes in nonstationary systems. For the
      latter, extreme wind speeds are examined in a simple quasigeostrophic model with
      a robust chaotic attractor subject to nonstationary forcing.

PMID- 20059224
TI  - Analysis of vibrational resonance in a quintic oscillator.
AB  - We consider a damped quintic oscillator with double-well and triple-well
      potentials driven by both low-frequency force f cos (omega)t and high-frequency
      force g cos (Omega)t with Omega>>omega and analyze the occurrence of vibrational
      resonance. The response consists of a slow motion with frequency omega and a fast
      motion with frequency Omega. We obtain an approximate analytical expression for
      the response amplitude Q at the low-frequency omega. From the analytical
      expression of Q, we determine the values of omega and g (denoted as omega(VR) and
      g(VR)) at which vibrational resonance occurs. The theoretical predictions are
      found to be in good agreement with numerical results. We show that for fixed
      values of the parameters of the system, as omega varies, resonance occurs at most
      one value of omega. When the amplitude g is varied we found two and four
      resonances in the system with double-well and triple-well cases, respectively. We
      present examples of resonance (i) without cross-well motion and (ii) with cross
      well orbit far before and far after it. omega(VR) depends on the damping strength
      d while g(VR) is independent of d. Moreover, the effect of d is found to decrease
      the response amplitude Q.

PMID- 20059225
TI  - Computing the multifractal spectrum from time series: an algorithmic approach.
AB  - We show that the existing methods for computing the f(alpha) spectrum from a time
      series can be improved by using a new algorithmic scheme. The scheme relies on
      the basic idea that the smooth convex profile of a typical f(alpha) spectrum can
      be fitted with an analytic function involving a set of four independent
      parameters. While the standard existing schemes [P. Grassberger et al., J. Stat.
      Phys. 51, 135 (1988); A. Chhabra and R. V. Jensen, Phys. Rev. Lett. 62, 1327
      (1989)] generally compute only an incomplete f(alpha) spectrum (usually the top
      portion), we show that this can be overcome by an algorithmic approach, which is
      automated to compute the D(q) and f(alpha) spectra from a time series for any
      embedding dimension. The scheme is first tested with the logistic attractor with
      known f(alpha) curve and subsequently applied to higher-dimensional cases. We
      also show that the scheme can be effectively adapted for analyzing practical time
      series involving noise, with examples from two widely different real world
      systems. Moreover, some preliminary results indicating that the set of four
      independent parameters may be used as diagnostic measures are also included.

PMID- 20059226
TI  - Probabilistic evaluation of time series models: a comparison of several
      approaches.
AB  - Several methods are examined which allow to produce forecasts for time series in
      the form of probability assignments. The necessary concepts are presented,
      addressing questions such as how to assess the performance of a probabilistic
      forecast. A particular class of models, cluster weighted models (CWMs), is given
      particular attention. CWMs, originally proposed for deterministic forecasts, can
      be employed for probabilistic forecasting with little modification. Two examples
      are presented. The first involves estimating the state of (numerically simulated)
      dynamical systems from noise corrupted measurements, a problem also known as
      filtering. There is an optimal solution to this problem, called the optimal
      filter, to which the considered time series models are compared. (The optimal
      filter requires the dynamical equations to be known.) In the second example, we
      aim at forecasting the chaotic oscillations of an experimental bronze spring
      system. Both examples demonstrate that the considered time series models, and
      especially the CWMs, provide useful probabilistic information about the
      underlying dynamical relations. In particular, they provide more than just an
      approximation to the conditional mean.

PMID- 20059227
TI  - Self-organization in predominantly feedforward oscillator chains.
AB  - Results on the dynamics of certain predominantly feedforward networks of phase
      oscillators are presented. We start with a purely feedforward chain and show
      numerically that in certain parameter ranges, independent of the length of the
      chain, there is a global attractor that is effectively a two-dimensional torus.
      Specifically, we find that after the system has reached its steady state, the
      phases of all the oscillators in the chain at any one moment in time are
      determined entirely by the phases of the first two oscillators. In the cases
      tested this phenomenon is found to persist with the addition of feedback
      couplings whose strengths may be up to a significant fraction of the feedforward
      strengths.

PMID- 20059228
TI  - New measures of multimodality for the detection of a ghost stochastic resonance.
AB  - Large-amplitude (10-15 K) millennial-duration warming events, the Dansgaard
      Oeschger (DO) events, repeatedly occurred in the North Atlantic region during ice
      ages. So far, the trigger of these events is not known. To explain their
      recurrence pattern, a ghost stochastic resonance (GSR) scenario has been
      suggested, i.e., a dynamical scenario in which the events represent the
      subharmonic response to centennial-scale solar forcing plus noise. According to
      this hypothesis a multimodal phase distribution of the events is expected, which
      should be tested on the basis of climate records by means of time series
      analysis. A major obstacle in these tests, however, is the need of a statistical
      measure of regularity that can distinguish between a random occurrence of DO
      events and a GSR scenario. Here we construct and compare three new measures of
      phase multimodality. In a Monte Carlo simulation with a simple conceptual model
      of DO events we simulate probability distributions of the measures under both
      scenarios for realizations of only 11 DO events. Based on these distributions we
      find that our measures are able to distinguish between a random occurrence and a
      GSR scenario. We further apply our measures to analyze the recurrence pattern of
      the last 11 DO events in the North Greenland Ice Core Project deep ice core from
      Greenland.

PMID- 20059229
TI  - Comment on "Anticipating synchronization of chaotic systems with time delay and
      parameter mismatch" [Chaos 19, 013104 (2009)].
AB  - In the referenced paper, the proof of Theorem 1 makes use of an incorrect
      inequality. Hence, there are concerns with conclusions drawn when the result is
      used to investigate anticipating synchronization for chaotic systems with time
      delay and parameter mismatch in the framework of the master-slave configuration.

PMID- 20059232
TI  - Combined optical and electrical stimulation of neural tissue in vivo.
AB  - Low-intensity, pulsed infrared light provides a novel nerve stimulation modality
      that avoids the limitations of traditional electrical methods such as necessity
      of contact, presence of a stimulation artifact, and relatively poor spatial
      precision. Infrared neural stimulation (INS) is, however, limited by a 2:1 ratio
      of threshold radiant exposures for damage to that for stimulation. We have shown
      that this ratio is increased to nearly 6:1 by combining the infrared pulse with a
      subthreshold electrical stimulus. Our results indicate a nonlinear relationship
      between the subthreshold depolarizing electrical stimulus and additional optical
      energy required to reach stimulation threshold. The change in optical threshold
      decreases linearly as the delay between the electrical and optical pulses is
      increased. We have shown that the high spatial precision of INS is maintained for
      this combined stimulation modality. Results of this study will facilitate the
      development of applications for infrared neural stimulation, as well as target
      the efforts to uncover the mechanism by which infrared light activates neural
      tissue.

PMID- 20059233
TI  - Physiological fluorescence lifetime imaging microscopy improves Forster resonance
      energy transfer detection in living cells.
AB  - Accurate, unambiguous detection of molecular interactions in living cells via
      measurements of Forster (or fluorescence) resonance energy transfer (FRET) events
      is experimentally challenging. We develop and apply a physiological fluorescence
      lifetime imaging microscopy (physiological FLIM) system to significantly improve
      FRET detection in living cells. Multiple positive and negative cellular controls
      are implemented to validate the experimental method developed. FLIM measurement
      techniques were found to remove fluorescence intensity-based artifacts, resulting
      in a seven-fold improvement in fluorescence measurement precision. The addition
      of cellular environmental controls, including both temperature and CO(2)
      stabilization, for physiological FLIM eliminates nonspecific FRET in the live
      cell system studied. Overall, only physiological FLIM results in statistically
      significant results that clearly indicated the presence of specific molecular
      interactions in the live-cell system. This approach can be applied generally to
      improve the accuracy and precision of FRET measurements in living cells.

PMID- 20059234
TI  - In vivo early detection of smoke-induced airway injury using three-dimensional
      swept-source optical coherence tomography.
AB  - We report on the feasibility of rapid, high-resolution, 3-D swept-source optical
      coherence tomography (SSOCT) to detect early airway injury changes following
      smoke inhalation exposure in a rabbit model. The SSOCT system obtains 3-D helical
      scanning using a microelectromechanical system motor-based endoscope. Real-time 2
      D data processing and image display at the speed of 20 frames/s are achieved by
      adopting the technique of parallel computing. Longitudinal images are
      reconstructed via an image processing algorithm to remove motion artifacts caused
      by ventilation and pulse. Quantitative analyses of tracheal airway thickness as
      well as thickness distribution along tracheal circumference are also performed
      based on the comprehensive 3-D volumetric data.

PMID- 20059235
TI  - Whole-body, real-time preclinical imaging of quantum dot fluorescence with time
      gated detection.
AB  - We describe a wide-field preclinical imaging system optimized for time-gated
      detection of quantum dot fluorescence emission. As compared to continuous wave
      measurements, image contrast was substantially improved by suppression of short
      lifetime background autofluorescence. Real-time (8 frames/s) biological imaging
      of subcutaneous quantum dot injections is demonstrated simultaneously in multiple
      living mice.

PMID- 20059236
TI  - In vivo harmonic generation biopsy of human skin.
AB  - The ability to in vivo image deep tissues noninvasively with a high resolution is
      strongly required for optical virtual biopsy. Higher harmonic generation
      microscopy, combined with second- and third-harmonic generation microscopies, is
      applied to 17 Asian volunteers' forearm skin. After continuous observation for 30
      min, no visible damage was found. Our study proves that harmonic generation
      biopsy (HGB) is able to satisfy the safety requirement and to provide high
      penetrability (approximately 300 microm) and submicron resolution all at the same
      time and is a promising tool for future virtual biopsy of skin diseases. In
      contrast to a previous study on fixed human skin specimens, a much improved
      penetrability and much reduced resolution-degradation versus depth are found in
      this in vivo examination.

PMID- 20059237
TI  - Real-time display on Fourier domain optical coherence tomography system using a
      graphics processing unit.
AB  - Fourier domain optical coherence tomography (FD-OCT) requires resampling of
      spectrally resolved depth information from wavelength to wave number, and the
      subsequent application of the inverse Fourier transform. The display rates of OCT
      images are much slower than the image acquisition rates due to processing speed
      limitations on most computers. We demonstrate a real-time display of processed
      OCT images using a linear-in-wave-number (linear-k) spectrometer and a graphics
      processing unit (GPU). We use the linear-k spectrometer with the combination of a
      diffractive grating with 1200 lines/mm and a F2 equilateral prism in the 840-nm
      spectral region to avoid calculating the resampling process. The calculations of
      the fast Fourier transform (FFT) are accelerated by the GPU with many stream
      processors, which realizes highly parallel processing. A display rate of 27.9
      frames/sec for processed images (2048 FFT size x 1000 lateral A-scans) is
      achieved in our OCT system using a line scan CCD camera operated at 27.9 kHz.

PMID- 20059238
TI  - Feasibility of Doppler variance imaging for red blood cell aggregation
      characterization.
AB  - An abnormal level of red blood cell (RBC) aggregation is a clinical condition
      associated with many pathologies. Our purpose is to investigate the feasibility
      of spectral domain phase-resolved optical Doppler tomography incorporated with
      Doppler variance imaging to characterize RBC aggregation in flowing blood.
      Variance/standard deviation (SD) of the Doppler frequency spectrum of porcine
      blood flowing through a glass tube (diameter 300 microm) at 4.7 mms is measured.
      For nonaggregating RBCs with hematocrits of 20, 40, and 60%, the mean centerline
      SD values were 34.2+/-1.2, 47.8+/-1.0, and 47.2+/-0.5, respectively. After
      dextran 500 induction, the SD value decreased significantly to 29.9+/-0.7, 37.9+/
      3.0, and 40.1+/-0.6 (P<0.01) in the aggregated blood, respectively. The results
      demonstrate that Doppler variance imaging using the SD value is capable of
      differentiating normal and aggregated blood.

PMID- 20059239
TI  - Bimodal ultrasound and fluorescence approach for prostate cancer diagnosis.
AB  - Finding a way to combine ultrasound and fluorescence optical imaging on an
      endorectal probe may improve early detection of prostate cancer. The ultrasound
      provides morphological information about the prostate, while the optical system
      detects and locates fluorophore-marked tumors. A tissue-mimicking phantom, which
      is representative of prostate tissues both on its optical (absorption mu(a) and
      diffusion mu(s) (')) and its ultrasound properties, has been made by our team. A
      transrectal probe adapted to fluorescence diffuse optical tomography measurements
      was also developed. Measurements were taken on the prostate phantom with this
      probe based on a pulsed laser and a time-resolved detection system. A
      reconstruction algorithm was then used to help locate and quantify fluorescent
      inclusions of different concentrations at fixed depths.

PMID- 20059240
TI  - Quantitative three-dimensional photoacoustic tomography of the finger joints: an
      in vivo study.
AB  - We present for the first time in vivo full three-dimensional (3-D) photoacoustic
      tomography (PAT) of the distal interphalangeal joint in a human subject. Both
      absorbed energy density and absorption coefficient images of the joint are
      quantitatively obtained using our finite-element-based photoacoustic image
      reconstruction algorithm coupled with the photon diffusion equation. The results
      show that major anatomical features in the joint along with the side arteries can
      be imaged with a 1-MHz transducer in a spherical scanning geometry. In addition,
      the cartilages associated with the joint can be quantitatively differentiated
      from the phalanx. This in vivo study suggests that the 3-D PAT method described
      has the potential to be used for early diagnosis of joint diseases such as
      osteoarthritis and rheumatoid arthritis.

PMID- 20059241
TI  - Parametric image reconstruction using the discrete cosine transform for optical
      tomography.
AB  - It is well known that the inverse problem in optical tomography is highly ill
      posed. The image reconstruction process is often unstable and nonunique, because
      the number of the boundary measurements data is far fewer than the number of the
      unknown parameters to be reconstructed. To overcome this problem, one can either
      increase the number of measurement data (e.g., multispectral or multifrequency
      methods), or reduce the number of unknowns (e.g., using prior structural
      information from other imaging modalities). We introduce a novel approach for
      reducing the unknown parameters in the reconstruction process. The discrete
      cosine transform (DCT), which has long been used in image compression, is here
      employed to parameterize the reconstructed image. In general, only a few DCT
      coefficients are needed to describe the main features in an optical tomographic
      image. Thus, the number of unknowns in the image reconstruction process can be
      drastically reduced. We show numerical and experimental examples that illustrate
      the performance of the new algorithm as compared to a standard model-based
      iterative image reconstructions scheme. We especially focus on the influence of
      initial guesses and noise levels on the reconstruction results.

PMID- 20059242
TI  - Quantitative characterization of optical and physiological parameters in normal
      breasts using time-resolved spectroscopy: in vivo results of 19 Singapore women.
AB  - We report the quantitative measurements of optical and physiological parameters
      of normal breasts from 19 Singapore women by using time-resolved diffuse optical
      spectroscopy. Intrinsic absorption coefficient (mu(a)) and reduced scattering
      coefficients (mu(s) (')) of breasts were calculated from the time-resolved photon
      migration data. Physiology of breasts was characterized using the concentrations
      of oxyhemoglobin, deoxyhemoglobin, total hemoglobin (THC), and oxygenation
      saturation. On average, the experiment results showed that the mu(a) of young
      women (below 40 years old) was 36 to 38% greater than that of older women (above
      40 years old) and that parameter THC was approximately 42% greater. Results also
      showed that the THC of premenopausal women was 24.3 microMol/L, which was
      approximately 69% larger than that of postmenopausal women at 14.1 microMol/L.
      Meanwhile, the mu(a) of premenopausal women was approximately 60% larger than
      that of postmenopausal women. Correlation analysis further showed that the
      optical and physiological parameters of breasts were strongly influenced by
      changes in the women's age, menopausal states, and body mass index. These in vivo
      experiment results will contribute to the breast tissue diagnosis between healthy
      and diseased breast tissues.

PMID- 20059243
TI  - Intracellular particle tracking as a tool for tumor cell characterization.
AB  - We studied the dynamics of two types of intracellular probe particles,
      ballistically injected latex spheres and endogenous granules, in tumor cell lines
      of different metastatic potential: breast tumor cells (MCF-7 malignant, MCF-10A
      benign) and pancreas adenocarcinoma (PaTu8988T malignant, PaTu8988S benign). For
      both tissue types and for both probes, the mean squared displacement (MSD)
      function measured in the malignant cells was substantially larger than in the
      benign cells. Only a few cells were needed to characterize the tissue as
      malignant or benign based on their MSD, since variations in MSD within the same
      cell line were relatively small. These findings suggest that intracellular
      particle tracking (IPT) can serve as a simple and reliable method for
      characterization of cell states obtained from a small amount of cell sample.
      Mechanical analysis of the same cell lines with atomic force microscopy (AFM) in
      force-distance mode revealed that AFM could distinguish between the benign and
      malignant breast cancer cells but not the pancreatic tumor cell lines. This
      underlines the potential value of IPT as a complementary nanomechanical tool for
      studying cell-state-dependent mechanical properties.

PMID- 20059244
TI  - Drug and light dose responses to focal photodynamic therapy of single blood
      vessels in vivo.
AB  - As part of an ongoing program to develop two-photon (2-gamma) photodynamic
      therapy (PDT) for treatment of wet-form age-related macular degeneration (AMD)
      and other vascular pathologies, we have evaluated the reciprocity of drug-light
      doses in focal-PDT. We targeted individual arteries in a murine window chamber
      model, using primarily the clinical photosensitizer Visudyne/liposomal
      verteporfin. Shortly after administration of the photosensitizer, a small region
      including an arteriole was selected and irradiated with varying light doses.
      Targeted and nearby vessels were observed for a maximum of 17 to 25 h to assess
      vascular shutdown, tapering, and dye leakage/occlusion. For a given end-point
      metric, there was reciprocity between the drug and light doses, i.e., the
      response correlated with the drug-light product (DLP). These results provide the
      first quantification of photosensitizer and light dose relationships for
      localized irradiation of a single blood vessel and are compared to the DLP
      required for vessel closure between 1-gamma and 2-gamma activation, between focal
      and broad-beam irradiation, and between verteporfin and a porphyrin dimer with
      high 2-gamma cross section. Demonstration of reciprocity over a wide range of DLP
      is important for further development of focal PDT treatments, such as the
      targeting of feeder vessels in 2-gamma PDT of AMD.

PMID- 20059245
TI  - Whole-body three-dimensional optoacoustic tomography system for small animals.
AB  - We develop a system for three-dimensional whole-body optoacoustic tomography of
      small animals for applications in preclinical research. The tomographic images
      are obtained while the objects of study (phantoms or mice) are rotated within a
      sphere outlined by a concave arc-shaped array of 64 piezocomposite transducers.
      Two pulsed lasers operating in the near-IR spectral range (755 and 1064 nm) with
      an average pulsed energy of about 100 mJ, a repetition rate of 10 Hz, and a pulse
      duration of 15 to 75 ns are used as optical illumination sources. During the
      scan, the mouse is illuminated orthogonally to the array with two wide beams of
      light from a bifurcated fiber bundle. The system is capable of generating images
      of individual organs and blood vessels through the entire body of a mouse with
      spatial resolution of approximately 0.5 mm.

PMID- 20059246
TI  - Dynamic eye phantom for retinal oximetry measurements.
AB  - Measurements of oxygen saturation and flow in the retina can yield information
      about eye health and the onset of eye pathologies such as diabetic retinopathy.
      Recently, we developed a multiaperture camera that uses the division of the
      retinal image into several wavelength-sensitive subimages to compute retinal
      oxygen saturation. The calibration of such instruments is particularly difficult
      due to the layered structure of the eye and the lack of alternative measurement
      techniques. For this purpose, we realize an in vitro model of the human eye
      composed of a lens, the retina vessel, and three layers: the choroid, the retinal
      pigmented epithelium, and the sclera. The retinal vessel is modeled with a
      microtube connected to a micropump and a hemoglobin reservoir in a closed
      circulatory system. Hemoglobin oxygenation in the vessel could be altered using a
      reversible fuel cell. The sclera is represented by a Spectralon slab. The optical
      properties of the other layers are mimicked using titanium dioxide as a
      scatterer, ink as an absorber, and epoxy as a supporting structure. The optical
      thickness of each layer of the eye phantom is matched to each respective eye
      layer.

PMID- 20059247
TI  - Fluorescence lifetime discrimination using expectation-maximization algorithm
      with joint deconvolution.
AB  - The fluorescence lifetime technique offers an effective way to resolve
      fluorescent components with overlapping emission spectra. The presence of
      multiple fluorescent components in biological compounds can hamper their
      discrimination. The conventional method based on the nonlinear least-squares
      technique is unable to consistently determine the correct number of fluorescent
      components in a fluorescence decay profile. This can limit the applications of
      the fluorescence lifetime technique in biological assays and diagnoses where more
      than one fluorescent component is typically encountered. We describe the use of
      an expectation-maximization (EM) method with joint deconvolution to estimate the
      fluorescence decay parameters, and the Bayesian information criterion (BIC) to
      accurately determine the number of fluorescent components. A comprehensive
      simulation and experimental study is carried out to compare the performance and
      accuracy of the proposed method. The results show that the EM-BIC method is able
      to accurately identify the correct number of fluorescent components in samples
      with weakly fluorescing components.

PMID- 20059248
TI  - Three-dimensional reconstruction in free-space whole-body fluorescence tomography
      of mice using optically reconstructed surface and atlas anatomy.
AB  - We present a 3-D image reconstruction method for free-space fluorescence
      tomography of mice using hybrid anatomical prior information. Specifically, we
      use an optically reconstructed surface of the experimental animal and a digital
      mouse atlas to approximate the anatomy of the animal as structural priors to
      assist image reconstruction. Experiments are carried out on a cadaver of a nude
      mouse with a fluorescent inclusion (2.4-mm-diam cylinder) implanted in the chest
      cavity. Tomographic fluorescence images are reconstructed using an iterative
      algorithm based on a finite element method. Coregistration of the fluorescence
      reconstruction and micro-CT (computed tomography) data acquired afterward show
      good localization accuracy (localization error 1.2+/-0.6 mm). Using the optically
      reconstructed surface, but without the atlas anatomy, image reconstruction fails
      to show the fluorescent inclusion correctly. The method demonstrates the utility
      of anatomical priors in support of free-space fluorescence tomography.

PMID- 20059249
TI  - In-vivo fluorescence imaging with a multivariate curve resolution spectral
      unmixing technique.
AB  - Spectral unmixing is a useful technique in fluorescence imaging for reducing the
      effects of native tissue autofluorescence and separating multiple fluorescence
      probes. While spectral unmixing methods are well established in fluorescence
      microscopy, they typically rely on precharacterized in-vitro spectra for each
      fluorophore. However, there are unique challenges for in-vivo applications, since
      the tissue absorption and scattering can have a significant impact on the
      measured spectrum of the fluorophore, and therefore make the in-vivo spectra
      substantially different to that of in vitro. In this work, we introduce a
      spectral unmixing algorithm tailored for in-vivo optical imaging that does not
      rely on precharacterized spectral libraries. It is derived from a multivariate
      curve resolution (MCR) method, which has been widely used in studies of
      chemometrics and gene expression. Given multispectral images and a few
      straightforward constraints such as non-negativity, the algorithm automatically
      finds the signal distribution and the pure spectrum of each component. Signal
      distribution maps help separate autofluorescence from other probes in the raw
      images and hence provide better quantification and localization for each probe.
      The algorithm is demonstrated with an extensive set of in-vivo experiments using
      near-infrared dyes and quantum dots in both epi-illumination and
      transillumination geometries.

PMID- 20059250
TI  - Real-time intraoperative fluorescence imaging system using light-absorption
      correction.
AB  - We present a novel fluorescence imaging system developed for real-time
      interventional imaging applications. The system implements a correction scheme
      that improves the accuracy of epi-illumination fluorescence images for light
      intensity variation in tissues. The implementation is based on the use of three
      cameras operating in parallel, utilizing a common lens, which allows for the
      concurrent collection of color, fluorescence, and light attenuation images at the
      excitation wavelength from the same field of view. The correction is based on a
      ratio approach of fluorescence over light attenuation images. Color images and
      video is used for surgical guidance and for registration with the corrected
      fluorescence images. We showcase the performance metrics of this system on
      phantoms and animals, and discuss the advantages over conventional epi
      illumination systems developed for real-time applications and the limits of
      validity of corrected epi-illumination fluorescence imaging.

PMID- 20059251
TI  - Wavelength-dependent backscattering measurements for quantitative real-time
      monitoring of apoptosis in living cells.
AB  - Apoptosis--programmed cell death--is a cellular process exhibiting distinct
      biochemical and morphological changes. An understanding of the early
      morphological changes that a cell undergoes during apoptosis can provide the
      opportunity to monitor apoptosis in tissue, yielding diagnostic and prognostic
      information. There is avid interest regarding the involvement of apoptosis in
      cancer. The initial response of a tumor to successful cancer treatment is often
      massive apoptosis. Current apoptosis detection methods require cell culture
      disruption. Our aim is to develop a nondisruptive optical method to monitor
      apoptosis in living cells and tissues. This would allow for real-time evaluation
      of apoptotic progression of the same cell culture over time without alteration.
      Elastic scattering spectroscopy (ESS) is used to monitor changes in light
      scattering properties of cells in vitro due to apoptotic morphology changes. We
      develop a simple instrument capable of wavelength-resolved ESS measurements from
      cell cultures in the backward direction. Using Mie theory, we also develop an
      algorithm that extracts the size distribution of scatterers in the sample. The
      instrument and algorithm are validated with microsphere suspensions. For cell
      studies, Chinese hamster ovary (CHO) cells are cultured to confluence on plates
      and are rendered apoptotic with staurosporine. Backscattering measurements are
      performed on pairs of treated and control samples at a sequence of times up to 6
      h post-treatment. Initial results indicate that ESS is capable of discriminating
      between treated and control samples as early as 10- to 15-min post-treatment,
      much earlier than is sensed by standard assays for apoptosis. Extracted size
      distributions from treated and control samples show a decrease in Rayleigh and
      150-nm scatterers, relative to control samples, with a corresponding increase in
      200-nm particles. Work continues to correlate these size distributions with
      underlying morphology. To our knowledge, this is the first report of the use of
      backscattering spectral measurements to quantitatively monitor apoptosis in
      viable cell cultures in vitro.

PMID- 20059253
TI  - Analysis of bacterial chemotactic response using dynamic laser speckle.
AB  - Chemotaxis has a meaningful role in several fields, such as microbial physiology,
      medicine and biotechnology. We present a new application of dynamic laser speckle
      (or biospeckle) to detect different degrees of bacterial motility during
      chemotactic response experiments. Encouraging results showed different bacterial
      dynamic responses due to differences in the hardness of the support in the
      swarming plates. We compare this method to a conventional technique that uses
      white light. Both methods showed to be analogous and, in some cases,
      complementary. The results suggest that biospeckle processed images can be used
      as an alternative method to evaluate bacterial chemotactic response and can
      supply additional information about the bacterial motility in different areas of
      the swarm plate assay that might be useful for biological analysis.

PMID- 20059252
TI  - Evaluation and clinically relevant applications of a fluorescent imaging analog
      to fluorodeoxyglucose positron emission tomography.
AB  - A fluorescent analog to 2-deoxy-2 [(18)F] fluoro-D-glucose position emission
      tomography (FDG-PET) would allow for the introduction of metabolic imaging into
      intraoperative and minimally invasive settings. We present through in vitro and
      in vivo experimentation an evaluation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)-2-deoxyglucose (2-NBDG), a fluorescently labeled glucose molecule, as a
      molecular beacon of glucose utilization. The competitive inhibition of 2-NBDG
      uptake by excess free glucose is directly compared against FDG uptake inhibition
      in cultured cells. 2-NBDG uptake in the brain of a mouse experiencing a
      generalized seizure is measured, as well as in subcutaneously implanted tumors in
      mice during fed and fasting states. Localization of 2-NBDG into malignant tissues
      is studied by laser scanning microscopy. The clinical relevance of 2-NBDG imaging
      is examined by performing fluorescence colonoscopy, and by correlating
      preoperative FDG-PET with intraoperative fluorescence imaging. 2-NBDG exhibits a
      similar uptake inhibition to FDG by excess glucose in the growth media. Uptake is
      significantly increased in the brain of an animal experiencing seizures versus
      control, and in subcutaneous tumors after the animals are kept nil per os (NPO)
      for 24 h versus ad libitum feeding. The clinical utility of 2-NBDG is confirmed
      by the demonstration of very high target-to-background ratios in minimally
      invasive and intraoperative imaging of malignant lesions. We present an optical
      analog of FDG-PET to extend the applicability of metabolic imaging to minimally
      invasive and intraoperative settings.

PMID- 20059254
TI  - In vitro conjunctival incision repair by temperature-controlled laser soldering.
AB  - The common method of closing conjunctival incisions is by suturing, which is
      associated with several disadvantages. It requires skill to apply and does not
      always provide a watertight closure, which is required in some operations (e.g.,
      glaucoma filtration). The purpose of the present study was to evaluate laser
      soldering as an alternative method for closing conjunctival incisions.
      Conjunctival incisions of 20 ex vivo porcine eyes were laser soldered using a
      temperature-controlled fiberoptic laser system and an albumin mixed with
      indocyanine green as a solder. The control group consisted of five repaired
      incisions by a 10-0 nylon running suture. The leak pressure of the repaired
      incisions was measured. The mean leak pressure in the laser-soldered group was
      132 mm Hg compared to 4 mm Hg in the sutured group. There was no statistically
      significant difference in both the incision's length and distance from the limbus
      between the groups, before and after the procedure, indicating that there was no
      severe thermal damage. These preliminary results clearly demonstrate that laser
      soldering may be a useful method for achieving an immediate watertight
      conjunctival wound closure. This procedure is faster and easier to apply than
      suturing.

PMID- 20059255
TI  - Effects of formalin fixing on the terahertz properties of biological tissues.
AB  - We demonstrate how the terahertz properties of porcine adipose tissue and
      skeletal muscle are affected by formalin fixing. Terahertz radiation is sensitive
      to covalently cross-linked proteins and can be used to probe unique spectroscopic
      signatures. We study in detail the changes arising from different fixation times
      and see that formalin fixing reduces the refractive index and the absorption
      coefficient of the samples in the terahertz regime. These fundamental properties
      affect the time-domain terahertz response of the samples and determine the level
      of image contrast that can be achieved.

PMID- 20059256
TI  - Ultrafast pulse-pair control in multiphoton fluorescence laser-scanning
      microscopy.
AB  - In multiphoton fluorescence laser-scanning microscopy, ultrafast laser pulses
      [i.e., light pulses having pulse width <or=1 ps (1 ps=10(-12) s)] are commonly
      employed to circumvent the low-multiphoton absorption cross-sections of common
      fluorophores. Because of the broad overlapping two-photon absorption spectra of
      fluorophores and the large spectral bandwidth of a short pulse, simultaneous
      excitation of many fluorophores is common, which justifies a persistent demand
      for selective excitation of individual fluorophores. We describe the use of pulse
      pair excitation with possibilities of controlling molecular fluorescence in laser
      scanning microscopy and compare it with coherent control using pulse sequence [De
      and Goswami, "Coherent control in multiphoton fluorescence imaging," Proc. SPIE
      7183, 71832B (2009)].

PMID- 20059257
TI  - Mechanical tissue optical clearing devices: evaluation of enhanced light
      penetration in skin using optical coherence tomography.
AB  - We report results of a study to evaluate effectiveness of a mechanical tissue
      optical clearing device (TOCD) using optical coherence tomography (OCT). The TOCD
      uses a pin array and vacuum pressure source to compress localized regions of the
      skin surface. OCT images (850 and 1310 nm) of in vivo human skin indicate
      application of the TOCD provides an up to threefold increased light penetration
      depth at spatial positions correlated with pin indentations. Increased contrast
      of the epidermal-dermal junction in OCT images spatially correlates with indented
      zones. OCT M-scans recorded while applying the TOCD indicate optical penetration
      depth monotonically increased, with most improvement at early times (5 to 10 s)
      of TOCD vacuum application. OCT M-scans of ex vivo porcine skin compressed using
      the TOCD suggest average group refractive index of the tissue increased,
      corresponding to a decrease in water concentration. Results of our study indicate
      that mechanical optical clearing of skin may provide an effective and efficient
      means to deliver increased light fluence to dermal and subdermal regions.

PMID- 20059258
TI  - Office-based dynamic imaging of vocal cords in awake patients with swept-source
      optical coherence tomography.
AB  - Optical coherence tomography (OCT) is an evolving noninvasive imaging modality
      that has been used to image the human larynx during surgical endoscopy. The
      design of a long gradient index (GRIN) lens-based probe capable of capturing
      images of the human larynx by use of swept-source OCT during a typical office
      based laryngoscopy examination is presented. In vivo OCT imaging of the human
      larynx is demonstrated with a rate of 40 frames per second. Dynamic vibration of
      the vocal folds is recorded to provide not only high-resolution cross-sectional
      tissue structures but also vibration parameters, such as the vibration frequency
      and magnitude of the vocal cords, which provides important information for
      clinical diagnosis and treatment, as well as fundamental research of the voice
      itself. Office-based OCT is a promising imaging modality to study the larynx for
      physicians in otolaryngology.

PMID- 20059259
TI  - Micropillar fabrication on bovine cortical bone by direct-write femtosecond laser
      ablation.
AB  - We investigated fabrication of cylindrical micropillars on bovine cortical bone
      using direct-write femtosecond laser ablation. The ablation threshold of the
      material was measured by single-pulse ablation tests, and the incubation
      coefficient was measured from linear scanned ablation tests. A motion system was
      programmed to apply multiple layers of concentric rings of pulses to machine
      pillars of various diameters and heights. The diameter of the top surface of the
      pillar was found to steadily decrease due to incubation of damage from successive
      layers of pulses during the machining process. Pillar top diameter was predicted
      based on a paraxial beam fluence approximation and single-pulse ablation
      threshold and incubation coefficient measurements. Pillar diameters predicted as
      successive layers of pulses were applied were well-matched to experiments,
      confirming that femtosecond laser ablation of the cortical bone was well-modeled
      by single-pulse ablation threshold measurements and an incubation coefficient.

PMID- 20059260
TI  - Confocal detection of planar homogeneous and heterogeneous immunosorbent assays.
AB  - Optically sectioned detection of fluorescence immunoassays using a confocal
      microscope enables the creation of both homo- and heterogeneous planar format
      assays. We report a set assays requiring optically sectioned detection using a
      model system and analysis procedures for separating signals of a surface layer
      from an overlying solution. A model sandwich assay with human immunoglobulin G as
      the target antigen is created on a glass substrate. The prepared surfaces are
      exposed to antigen and a FITC-labeled secondary antibody. The resulting
      preparations are either read directly to provide a homogeneous assay or after
      wash steps, giving a heterogeneous assay. The simplicity of the object shapes
      arising from the planar format makes the decomposition of analyte signals from
      the thin film bound to the surface and overlayer straightforward. Measured
      response functions of the thin film and overlayer fit well to the Cauchy-Lorentz
      and cumulative Cauchy-Lorentz functions, respectively, enabling the film and
      overlayer to be separated. Under the conditions used, the detection limits for
      the homogeneous and heterogeneous forms of the assay are 2.2 and 5.5 ng/ml,
      respectively. Planar format, confocally read fluorescence assays enable wash-free
      detection of antigens and should be applicable to a wide range of assays
      involving surface-bound species.

PMID- 20059261
TI  - Reliability and reproducibility of macular segmentation using a custom-built
      optical coherence tomography retinal image analysis software.
AB  - We determine the reliability and reproducibility of retinal thickness
      measurements with a custom-built OCT retinal image analysis software (OCTRIMA).
      Ten eyes of five healthy subjects undergo repeated standard macular thickness map
      scan sessions by two experienced examiners using a Stratus OCT device.
      Automatic/semi automatic thickness quantification of the macula and intraretinal
      layers is performed using OCTRIMA software. Intraobserver, interobserver, and
      intervisit repeatability and reproducibility coefficients, and intraclass
      correlation coefficients (ICCs) per scan are calculated. Intraobserver,
      interobserver, and intervisit variability combined account for less than 5% of
      total variability for the total retinal thickness measurements and less than 7%
      for the intraretinal layers except the outer segment/ retinal pigment epithelium
      (RPE) junction. There is no significant difference between scans acquired by
      different observers or during different visits. The ICCs obtained for the
      intraobserver and intervisit variability tests are greater than 0.75 for the
      total retina and all intraretinal layers, except the inner nuclear layer
      intraobserver and interobserver test and the outer plexiform layer,
      intraobserver, interobserver, and intervisit test. Our results indicate that
      thickness measurements for the total retina and all intraretinal layers (except
      the outer segment/RPE junction) performed using OCTRIMA are highly repeatable and
      reproducible.

PMID- 20059262
TI  - Spectral filtering in pulsed photothermal temperature profiling of collagen
      tissue phantoms.
AB  - We present an experimental comparison of pulsed photothermal (PPT) profiling in
      collagen-based tissue phantoms utilizing different midinfrared spectral bands.
      Laser-induced temperature profiles are reconstructed using a custom optimization
      code within the customary monochromatic approximation. Both experimental results
      and a detailed numerical simulation of the procedure demonstrate that, despite
      the associated reduction of signal-to-noise ratio, appropriate spectral filtering
      reduces the broadening of temperature peaks and thus improves the accuracy of
      temperature profiling. For our experimental system, best performance is obtained
      when applying a long-pass filter with cut-on wavelength at 3.4-3.8 microm.
      Because our collagen gel mimics infrared and thermal properties of human skin, we
      believe that this conclusion is transferrable to PPT radiometric profiling of
      human skin in vivo.

PMID- 20059263
TI  - Monte Carlo study of global interference cancellation by multidistance
      measurement of near-infrared spectroscopy.
AB  - The performance of near-infrared spectroscopy is sometimes degraded by the
      systemic physiological interference in the extracerebral layer. There is some
      systemic interference, which is highly correlated with the functional response
      evoked by a task execution. This kind of interference is difficult to remove by
      using ordinary techniques. A multidistance measurement method is one of the
      possible solutions for this problem. The multidistance measurement method
      requires estimation parameters derived from partial pathlength values of tissue
      layers to calculate an absorption coefficient change from a temporal absorbance
      change. Because partial path lengths are difficult to obtain, experimentally, we
      estimated them by a Monte Carlo simulation based on a five-layered slab model of
      a human adult head. Model parameters such as thickness and the transport
      scattering coefficient of each layer depend on a subject and a measurement
      position; thus, we assumed that these parameters obey normal distributions around
      standard parameter values. We determined the estimation parameters that provide a
      good separation performance in average for the model parameter distribution. The
      obtained weighting is robust to model parameter deviation and provides smaller
      errors on average compared to the parameters, which are determined without
      considering parameter distribution.

PMID- 20059264
TI  - Multispecies breath analysis faster than a single respiratory cycle by optical
      feedback cavity-enhanced absorption spectroscopy.
AB  - We demonstrate a first application, of optical-feedback cavity-enhanced
      absorption spectroscopy (OF-CEAS) to breath analysis in a medical environment.
      Noninvasive monitoring of trace species in exhaled air was performed simultaneous
      to spirometric measurements on patients at Bichat Hospital (Paris). The high
      selectivity of the OF-CEAS spectrometer and a time response of 0.3 s (limited by
      sample flow rate) allowed following the evolution of carbon monoxide and methane
      concentrations during individual respiratory cycles, and resolving variations
      among different ventilatory patterns. The minimum detectable absorption on this
      time scale is about 3 x 10(-10) cm(-1). At the working wavelength of the
      instrument (2.326 microm), this translates to concentration detection limits of
      approximately 1 ppbv (45 picomolar, or approximately 1.25 microg/m(3)) for CO and
      25 ppbv for CH(4), well below concentration values found in exhaled air. This
      same instrument is also able to provide measurement of NH(3) concentrations with
      a detection limit of approximately 10 ppbv; however, at present, memory effects
      do not allow its measurement on fast time scales.

PMID- 20059265
TI  - Shape-dependent sensitivity of single plasmonic nanoparticles for biosensing.
AB  - Shape-dependent sensitivity of localized surface plasmon-based biosensing was
      investigated by combining single-particle protein-sensing and multiple multipole
      program simulation. Significantly higher sensitivity was observed for tetrahedral
      particles than spherical ones, which was revealed by careful structural analysis
      of individually measured particles. The simulation of the corresponding particles
      with layered protein adsorption model showed consistent optical property and
      sensitivity, which were explained in terms of the field enhancement at the
      pointing edges.

PMID- 20059266
TI  - Reflection-contrast limit of fiber-optic image guides.
AB  - Fiber-optic image guides in confocal reflectance endomicroscopes introduce
      background backscatter that limits the achievable contrast in these devices. We
      show the dominant source of backscatter from the image guide is due to Rayleigh
      scattering at short wavelengths and terminal reflections of the fibers at long
      wavelengths. The effective Rayleigh scattering coefficient and the wavelength
      independent reflectivity due terminal reflections are measured experimentally in
      a commercial image guide. The Rayleigh scattering component of backscatter can be
      accurately predicted using the fractional refractive-index difference and length
      of the fibers in the image guide. We also presented a simple model that can be
      used to predict signal-to-background ratio in a fiber-optic confocal reflectance
      endomicroscope for biologically relevant tissues and contrast agents that cover a
      wide range of reflectivity.

PMID- 20059267
TI  - Examination of tear film smoothness on corneae after refractive surgeries using a
      noninvasive interferometric method.
AB  - A lateral shearing interferometer was used to examine the smoothness of the tear
      film. The information about the distribution and stability of the precorneal tear
      film is carried out by the wavefront reflected from the surface of tears and
      coded in interference fringes. Smooth and regular fringes indicate a smooth tear
      film surface. On corneae after laser in situ keratomileusis (LASIK) or radial
      keratotomy (RK) surgery, the interference fringes are seldom regular. The fringes
      are bent on bright lines, which are interpreted as tear film breakups. The high
      intensity pattern seems to appear in similar location on the corneal surface
      after refractive surgery. Our purpose was to extract information about the
      pattern existing under the interference fringes and calculate its shape
      reproducibility over time and following eye blinks. A low-pass filter was applied
      and correlation coefficient was calculated to compare a selected fragment of the
      template image to each of the following frames in the recorded sequence. High
      values of the correlation coefficient suggest that irregularities of the corneal
      epithelium might influence tear film instability and that tear film breakup may
      be associated with local irregularities of the corneal topography created after
      the LASIK and RK surgeries.

PMID- 20059268
TI  - Detecting precancerous lesions in the hamster cheek pouch using spectroscopic
      white-light optical coherence tomography to assess nuclear morphology via
      spectral oscillations.
AB  - We have developed a novel dual-window approach for spectroscopic optical
      coherence tomography (OCT) measurements and applied it to probe nuclear
      morphology in tissue samples drawn from the hamster cheek pouch carcinogenesis
      model. The dual-window approach enables high spectral and depth resolution
      simultaneously, allowing detection of spectral oscillations, which we isolate to
      determine the structure of cell nuclei in the basal layer of the epithelium. The
      measurements were executed with our parallel frequency domain OCT system, which
      uses light from a thermal source, providing high bandwidth and access to the
      visible portion of the spectrum. The structural measurements show a highly
      statistically significant difference between untreated (normal) and treated
      (hyperplastic/dysplastic) tissues, indicating the potential utility of this
      approach as a diagnostic method.

PMID- 20059269
TI  - Imaging of goblet cells as a marker for intestinal metaplasia of the stomach by
      one-photon and two-photon fluorescence endomicroscopy.
AB  - Goblet cells are a requirement for the diagnosis of intestinal metaplasia of the
      stomach. The gastric mucosa is lined by a monolayer of columnar epithelium with
      some specialization at the crypts, but there are no goblet cells in normal
      gastric epithelium. The appearance of goblet cells in gastric epithelium is an
      indicator of potential malignant progression toward adenocarcinoma. Therefore, in
      vivo three-dimensional imaging of goblet cells is essential for diagnoses of a
      premalignant stage of gastric cancers called intestinal metaplasia. We used mouse
      intestine, which has goblet cells, as a model of intestinal metaplasia. One
      photon confocal fluorescence endomicroscopy and two-photon fluorescence
      endomicroscopy are employed for 3-D imaging of goblet cells. The penetration
      depth, the sectioning ability, and the photobleaching information of imaging are
      demonstrated. Both endomicroscopy techniques can three-dimensionally observe
      goblet cells in mouse large intestine and achieve an imaging depth of 176 microm.
      The two-photon fluorescence endomicroscopy shows higher resolution and contrast
      of the imaging sections at each depth. In addition, two-photon fluorescence
      endomicroscopy also has advantages of sectioning ability and less photobleaching.
      These results prove that two-photon fluorescence endomicroscopy is advantageous
      in diagnoses of a premalignant stage of gastric cancers.

PMID- 20059270
TI  - Noninvasive assessment of diabetic foot ulcers with diffuse photon density wave
      methodology: pilot human study.
AB  - A pilot human study is conducted to evaluate the potential of using diffuse
      photon density wave (DPDW) methodology at near-infrared (NIR) wavelengths (685 to
      830 nm) to monitor changes in tissue hemoglobin concentration in diabetic foot
      ulcers. Hemoglobin concentration is measured by DPDW in 12 human wounds for a
      period ranging from 10 to 61 weeks. In all wounds that healed completely, gradual
      decreases in optical absorption coefficient, oxygenated hemoglobin concentration,
      and total hemoglobin concentration are observed between the first and last
      measurements. In nonhealing wounds, the rates of change of these properties are
      nearly zero or slightly positive, and a statistically significant difference
      (p<0.05) is observed in the rates of change between healing and nonhealing
      wounds. Differences in the variability of DPDW measurements over time are
      observed between healing and nonhealing wounds, and this variance may also be a
      useful indicator of nonhealing wounds. Our results demonstrate that DPDW
      methodology with a frequency domain NIR device can differentiate healing from
      nonhealing diabetic foot ulcers, and indicate that it may have clinical utility
      in the evaluation of wound healing potential.

PMID- 20059272
TI  - Multidistance probe arrangement to eliminate artifacts in functional near
      infrared spectroscopy.
AB  - Functional near-infrared spectroscopy has the potential to easily detect cerebral
      functional hemodynamics. However, in practical fNIRS measurements, a subject's
      physical or systemic physiological activities often cause undesirable artifacts.
      Such activities can be evoked even by task execution. In this case, observed
      artifacts may correlate strongly with the task sequence, and it is difficult to
      eliminate them by conventional signal filtering techniques. We present a
      theoretical analysis and Monte Carlo simulations of layered media in which both
      scattering and absorption changes occur, and show that a multidistance probe
      arrangement is effective in removing artifacts and extracting functional
      hemodynamics. The probe arrangement is determined based on simulation results.
      Artifacts induced by nonfunctional tasks (body tilting, head nodding, and breath
      holding) are clearly observed when a conventional method is used; such artifacts
      are appreciably reduced by the proposed method. Signals evoked by single-sided
      finger movements are observed at both hemispheres when we use a conventional
      method. On the other hand, localized signals at the primary motor area are
      observed by the proposed method. A statistically significant increase in
      oxygenated hemoglobin and decrease in deoxygenated hemoglobin are simultaneously
      observed at the contralateral primary motor area.

PMID- 20059271
TI  - Two-photon microscope for multisite microphotolysis of caged neurotransmitters in
      acute brain slices.
AB  - We developed a two-photon microscope optimized for physiologically manipulating
      single neurons through their postsynaptic receptors. The optical layout fulfills
      the stringent design criteria required for high-speed, high-resolution imaging in
      scattering brain tissue with minimal photodamage. We detail the practical
      compensation of spectral and temporal dispersion inherent in fast laser beam
      scanning with acousto-optic deflectors, as well as a set of biological protocols
      for visualizing nearly diffraction-limited structures and delivering
      physiological synaptic stimuli. The microscope clearly resolves dendritic spines
      and evokes electrophysiological transients in single neurons that are similar to
      endogenous responses. This system enables the study of multisynaptic integration
      and will assist our understanding of single neuron function and dendritic
      computation.

PMID- 20059273
TI  - Dual-modal three-dimensional imaging of single cells with isometric high
      resolution using an optical projection tomography microscope.
AB  - The practice of clinical cytology relies on bright-field microscopy using
      absorption dyes like hematoxylin and eosin in the transmission mode, while the
      practice of research microscopy relies on fluorescence microscopy in the epi
      illumination mode. The optical projection tomography microscope is an optical
      microscope that can generate 3-D images of single cells with isometric high
      resolution both in absorption and fluorescence mode. Although the depth of field
      of the microscope objective is in the submicron range, it can be extended by
      scanning the objective's focal plane. The extended depth of field image is
      similar to a projection in a conventional x-ray computed tomography. Cells
      suspended in optical gel flow through a custom-designed microcapillary. Multiple
      pseudoprojection images are taken by rotating the microcapillary. After these
      pseudoprojection images are further aligned, computed tomography methods are
      applied to create 3-D reconstruction. 3-D reconstructed images of single cells
      are shown in both absorption and fluorescence mode. Fluorescence spatial
      resolution is measured at 0.35 microm in both axial and lateral dimensions. Since
      fluorescence and absorption images are taken in two different rotations,
      mechanical error may cause misalignment of 3-D images. This mechanical error is
      estimated to be within the resolution of the system.

PMID- 20059274
TI  - Is there a difference between T- and B-lymphocyte morphology?
AB  - We characterize T- and B-lymphocytes from several donors, determining cell
      diameter, ratio of nucleus to cell diameter, and refractive index of the nucleus
      and cytoplasm for each individual cell. We measure light-scattering profiles with
      a scanning flow cytometer and invert the signals using a coated sphere as an
      optical model of the cell and by relying on a global optimization technique. The
      main difference in morphology of T- and B-lymphocytes is found to be the larger
      mean diameters of the latter. However, the difference is smaller than the natural
      biological variability of a single cell. We propose nuclear inhomogeneity as a
      possible reason for the deviation of measured light-scattering profiles from real
      lymphocytes from those obtained from the coated sphere model.

PMID- 20059275
TI  - Improved three-dimensional Fourier domain optical coherence tomography by index
      matching in alveolar structures.
AB  - Three-dimensional Fourier domain optical coherence tomography (3-D FDOCT) is used
      to demonstrate that perfusion fixation with a mixture of glutaraldehyde and
      paraformaldehyde does not alter the geometry of subpleural lung parenchyma in
      isolated and perfused rabbit lungs. This is confirmed by simultaneous imaging of
      lung parenchyma with intravital microscopy. To eliminate the diffraction index
      interfaces between alveolar pockets and walls, we fill the fixed lungs with
      ethanol by perfusing with gradually increasing concentrations. This bottom-up
      filling process leaves no remaining air bubbles in the alveolar structures, thus
      drastically improving the resolution and penetration depth of 3-D FDOCT imaging.
      We observe an approximately 18% increase in alveolar area after ethanol filling,
      likely due in large part to elimination of the air/tissue interfaces. 3-D OCT
      datasets acquired from ethanol-filled lungs allow segmentation of the ethanol
      filled structures, which were formerly air-filled, and 3-D reconstruction of
      larger areas of subpleural alveolar structures. Our innovative process of filling
      the lungs with ethanol postperfusion fixation thus enables more accurate
      quantification of alveolar geometries, a critical component of modeling lung
      function.

PMID- 20059276
TI  - Motion-gated acquisition for in vivo optical imaging.
AB  - Wide-field continuous wave fluorescence imaging, fluorescence lifetime imaging,
      frequency domain photon migration, and spatially modulated imaging have the
      potential to provide quantitative measurements in vivo. However, most of these
      techniques have not yet been successfully translated to the clinic due to
      challenging environmental constraints. In many circumstances, cardiac and
      respiratory motion greatly impair image quality and/or quantitative processing.
      To address this fundamental problem, we have developed a low-cost, field
      programmable gate array-based, hardware-only gating device that delivers a phase
      locked acquisition window of arbitrary delay and width that is derived from an
      unlimited number of pseudo-periodic and nonperiodic input signals. All device
      features can be controlled manually or via USB serial commands. The working range
      of the device spans the extremes of mouse electrocardiogram (1000 beats per
      minute) to human respiration (4 breaths per minute), with timing resolution
      <or=0.06%, and jitter <or=0.008%, of the input signal period. We demonstrate the
      performance of the gating device, including dramatic improvements in quantitative
      measurements, in vitro using a motion simulator and in vivo using near-infrared
      fluorescence angiography of beating pig heart. This gating device should help to
      enable the clinical translation of promising new optical imaging technologies.

PMID- 20059277
TI  - Robust estimation of tear film surface quality in lateral shearing
      interferometry.
AB  - Interferometry is a sensitive technique for recording tear film surface
      irregularities in a noninvasive manner. At the same time, the technique is
      hindered by natural eye movements resulting in measurement noise. Estimating tear
      film surface quality from interferograms can be reduced to a spatial-average
      localized weighted estimate of the first harmonic of the interference fringes.
      However, previously reported estimation techniques proved to perform poorly in
      cases where the pattern fringes were significantly disturbed. This can occur in
      cases of measuring tear film surface quality on a contact lens on the eye or in a
      dry eye. We present a new estimation technique for extracting the first harmonic
      from the interference fringes that combines the traditional spectral estimation
      techniques with morphological image processing techniques. The proposed technique
      proves to be more robust to changes in interference fringes caused by natural eye
      movements and the degree of dryness of the contact lens and corneal surfaces than
      its predecessors, resulting in tear film surface quality estimates that are less
      noisy.

PMID- 20059278
TI  - Comparison of Cornea Module and DermaInspect for noninvasive imaging of ocular
      surface pathologies.
AB  - Minimally invasive imaging of ocular surface pathologies aims at securing
      clinical diagnosis without actual tissue probing. For this matter, confocal
      microscopy (Cornea Module) is in daily use in ophthalmic practice. Multiphoton
      microscopy is a new optical technique that enables high-resolution imaging and
      functional analysis of living tissues based on tissue autofluorescence. This
      study was set up to compare the potential of a multiphoton microscope
      (DermaInspect) to the Cornea Module. Ocular surface pathologies such as pterygia,
      papillomae, and nevi were investigated in vivo using the Cornea Module and imaged
      immediately after excision by DermaInspect. Two excitation wavelengths,
      fluorescence lifetime imaging and second-harmonic generation (SHG), were used to
      discriminate different tissue structures. Images were compared with the
      histopathological assessment of the samples. At wavelengths of 730 nm,
      multiphoton microscopy exclusively revealed cellular structures. Collagen fibrils
      were specifically demonstrated by second-harmonic generation. Measurements of
      fluorescent lifetimes enabled the highly specific detection of goblet cells,
      erythrocytes, and nevus-cell clusters. At the settings used, DermaInspect reaches
      higher resolutions than the Cornea Module and obtains additional structural
      information. The parallel detection of multiphoton excited autofluorescence and
      confocal imaging could expand the possibilities of minimally invasive
      investigation of the ocular surface toward functional analysis at higher
      resolutions.

PMID- 20059279
TI  - Design considerations for surface plasmon resonance-based fiber-optic detection
      of human blood group.
AB  - A fiber-optic surface plasmon resonance (SPR) sensor for the detection of human
      blood groups is proposed. Previous experimental results describing the wavelength
      dependent refractive index variation of multiple samples of different blood
      groups are considered for theoretical calculations. The spectral interrogation
      method, along with silica fiber and silver layer, is considered. The sensor's
      performance is closely analyzed in terms of shift in SPR wavelength and SPR curve
      width in order to optimize the design parameters for a reliable and accurate
      blood-group identifier. The sensor design parameters include silver layer
      thickness, fiber core diameter, sensing region length, and temperature variation.
      The results are explained in terms of light coupling and plasmon resonance
      condition. The proposed sensing probe is able to provide high sensitivity and
      accuracy of blood-group detection, thereby opening an easy and reliable window
      for medical applications.

PMID- 20059280
TI  - Photonic approach to the selective inactivation of viruses with a near-infrared
      subpicosecond fiber laser.
AB  - We report a photonic approach for selective inactivation of viruses with a near
      infrared subpicosecond laser. We demonstrate that this method can selectively
      inactivate viral particles ranging from nonpathogenic viruses such as the M13
      bacteriophage and the tobacco mosaic virus to pathogenic viruses such as the
      human papillomavirus and the human immunodeficiency virus (HIV). At the same
      time, sensitive materials such as human Jurkat T cells, human red blood cells,
      and mouse dendritic cells remain unharmed. The laser technology targets the
      global mechanical properties of the viral protein shell, making it relatively
      insensitive to the local genetic mutation in the target viruses. As a result, the
      approach can inactivate both the wild and mutated strains of viruses. This
      intriguing advantage is particularly important in the treatment of diseases
      involving rapidly mutating viral species such as HIV. Our photonic approach could
      be used for the disinfection of viral pathogens in blood products and for the
      treatment of blood-borne viral diseases in the clinic.

PMID- 20059281
TI  - Accelerated adhesion of grafted skin by laser-induced stress wave-based gene
      transfer of hepatocyte growth factor.
AB  - Gene therapy using wound healing-associated growth factor gene has received much
      attention as a new strategy for improving the outcome of tissue transplantation.
      We delivered plasmid DNA coding for human hepatocyte growth factor (hHGF) to rat
      free skin grafts by the use of laser-induced stress waves (LISWs); autografting
      was performed with the grafts. Systematic analysis was conducted to evaluate the
      adhesion properties of the grafted tissue; angiogenesis, cell proliferation, and
      reepithelialization were assessed by immunohistochemistry, and reperfusion was
      measured by laser Doppler imaging as a function of time after grafting. Both the
      level of angiogenesis on day 3 after grafting and the increased ratio of blood
      flow on day 4 to that on day 3 were significantly higher than those in five
      control groups: grafting with hHGF gene injection alone, grafting with control
      plasmid vector injection alone, grafting with LISW application alone, grafting
      with LISW application after control plasmid vector injection, and normal
      grafting. Reepithelialization was almost completed on day 7 even at the center of
      the graft with LISW application after hHGF gene injection, while it was not for
      the grafts of the five control groups. These findings demonstrate the validity of
      our LISW-based HGF gene transfection to accelerate the adhesion of grafted skins.

PMID- 20059282
TI  - Immunohistochemical investigation of wound healing in response to fractional
      photothermolysis.
AB  - Despite growing clinical evidence of ablative fractional photothermolysis (AFP),
      little is known about the spatiotemporal molecular changes within the targeted
      compartments. Six subjects received three different single AFP treatments using a
      scanned 250 mum CO(2)-laser beam. Spatiotemporal changes of skin regeneration
      were estimated by immunohistochemical investigation (HSP70, HSP72, HSP47,
      TGFbeta, procollagen III, CD3, CD20, and CD68) in skin samples 1 h, 3 days, and
      14 days postintervention. The remodeling was uniformly started by regrowth of the
      epidermal compartment followed by partial to complete replacement of the
      microscopic ablation zones (MAZ) by newly synthesized condensed procollagen III.
      From day 3 to 14, the number of macrophages as well as giant cells surrounding
      the MAZ increased. TGFbeta expression was highest 1 h to 3 days following AFP.
      HSP70 and HSP72 expressions were highest 3-14 days postintervention in the
      spinocellular layer leading to an upregulation of HSP47. AFP performed by a
      scanned CO(2)-laser results in an early epidermal remodeling, which is followed
      by a dermal remodeling leading to a replacement of the MAZ with newly synthesized
      (pro)-collagen. During this, an inflammatory infiltrate with CD3(+) and CD20(+)
      cells surrounds the MAZ. The count of macrophages and giant cells involved in the
      replacement of the necrotic zones seems to be crucial for wound healing.

PMID- 20059283
TI  - In vivo three-dimensional imaging of normal tissue and tumors in the rabbit
      pleural cavity using endoscopic swept source optical coherence tomography with
      thoracoscopic guidance.
AB  - The purpose of this study was to develop a dynamic tunable focal distance graded
      refractive-index lens rod-based high-speed 3-D swept-source (SS) optical
      coherence tomography (OCT) endoscopic system and demonstrate real-time in vivo,
      high-resolution (10-microm) imaging of pleural-based malignancies in an animal
      model. The GRIN lens-based 3-D SS OCT system, which images at 39 fps with 512 A
      lines per frame, was able to capture images of and detect abnormalities during
      thoracoscopy in the thoracic cavity, including the pleura, chest wall,
      pericardium, and the lungs. The abnormalities were confirmed by histological
      evaluation and compared to OCT findings. The dynamic tunable focal distance range
      and rapid speed of the probe and SS prototype OCT system enabled this first
      reported application of in vivo 3-D thoracoscopic imaging of pleural-based
      malignancies. The imaging probe of the system was found to be easily adaptable to
      various sites within the thoracic cavity and can be readily adapted to other
      sites, including rigid airway endoscopic examinations.

PMID- 20059284
TI  - Correspondence between retinal reflectometry and a flicker-based technique in the
      measurement of macular pigment spatial profiles.
AB  - A comparison of macular pigment optical density (MPOD) spatial profiles
      determined by an optical and a psychophysical technique is presented. We measured
      the right eyes of 19 healthy individuals, using fundus reflectometry at 0, 1, 2,
      4, 6, and 8 deg eccentricity; and heterochromatic flicker photometry (HFP) at 0,
      0.5, 1, 2, 3, 4, 5, 6, and 7 deg, and a reference point at 8 deg eccentricity. We
      found a strong correlation between the two techniques. However, the absolute
      estimates obtained by fundus reflectometry data were higher than by HFP. These
      differences could partly be explained by the fact that at 8 deg eccentricity the
      MPOD is not zero, as assumed in HFP. Furthermore, when performing HFP for
      eccentricities of <1 deg, we had to assume that subjects set flicker thresholds
      at 0.4 deg horizontal translation when using a 1-deg stimulus. MPOD profiles are
      very similar for both techniques if, on average, 0.05 DU is added to the HFP data
      at all eccentricities. An additional correction factor, dependent on the
      steepness of the MPOD spatial distribution, is required for 0 deg.

PMID- 20059285
TI  - Near-infrared hyperspectral imaging of teeth for dental caries detection.
AB  - Near-infrared (NIR) is preferred for caries detection compared to visible light
      imaging because it exhibits low absorption by stain and deeper penetration into
      teeth. Hyperspectral images from 1000 to 2500 nm have been obtained for a total
      of 12 extracted teeth (premolars and molars) with different degrees of natural
      lesion. Analysis of the reflectance spectra suggests that light scattering by
      porous enamel and absorption by water in dentin can be used to quantify the
      lesion severity and generate a NIR caries score. Teeth were ground for
      histological examination after the measurements. The NIR caries score obtained
      correlates significantly (Spearman's correlation of 0.89, p<0.01) with the
      corresponding histological score. Results yield a sensitivity of >99% and a
      specificity of 87.5% for enamel lesions and a sensitivity of 80% and a
      specificity >99% for dentine lesions. The nature of the technique offers
      significant advantages, including the ability to map the lesion distribution
      rather than obtaining single-point measurements, it is also noninvasive,
      noncontact, and stain insensitive. These results suggest that NIR spectral
      imaging is a potential clinical technique for quantitative caries diagnosis and
      can determine the presence of occlusal enamel and dentin lesions.

PMID- 20059286
TI  - Clinical and economic outcomes associated with potentially inappropriate
      prescribing in the elderly.
AB  - OBJECTIVE: To evaluate the risk of adverse events (AEs) and the healthcare costs
      for elderly patients receiving specific potentially inappropriate medications
      (PIMs). STUDY DESIGN: Retrospective cohort study. METHODS: Patients 65 years and
      older who started 1 of 23 PIMs were matched with control subjects who were not
      receiving PIMs. The following 4 AEs and PIMs were evaluated: delirium or
      hallucinations with Beers high-severity (BHS) anticholinergics, delirium or
      hallucinations with BHS narcotics (meperidine hydrochloride or pentazocine
      lactate or pentazocine hydrochloride), extrapyramidal effects with
      trimethobenzamide hydrochloride, and falls or fractures with BHS sedative
      hypnotics. The risk of having the AE of interest within 360 days and the annual
      healthcare costs were examined. RESULTS: Patients receiving BHS sedative
      hypnotics were significantly more likely to have a fall or fracture than controls
      (hazard ratio, 1.22; 95% confidence interval [CI], 1.10-1.35). Patients receiving
      BHS anticholinergics did not have higher risk of delirium or hallucinations than
      controls (hazard ratio, 1.03; 95% CI, 0.91-1.16). Delirium or hallucinations
      occurred at a higher rate among patients receiving BHS narcotics, and
      extrapyramidal effects occurred at a higher rate among patients receiving
      trimethobenzamide; however, too few events occurred to assess statistical
      significance. For all PIMs evaluated, annual adjusted medical and total
      healthcare costs were significantly higher for patients exposed to PIMs than for
      controls. CONCLUSION: The use of certain BHS PIMs in the elderly may increase AEs
      or healthcare costs.

PMID- 20059287
TI  - The effect of a PPO pay-for-performance program on patients with diabetes.
AB  - OBJECTIVES: To investigate the effectiveness of a pay-for-performance program
      (P4P) to increase the receipt of quality care and to decrease hospitalization
      rates among patients with diabetes mellitus. STUDY DESIGN: Longitudinal study of
      patients with diabetes enrolled in a preferred provider organization (PPO)
      between January 1, 1999, and December 31, 2006. METHODS: We used multivariate
      analyses to assess the effect of seeing P4P-participating physicians on the
      receipt of quality care (ie, glycosylated hemoglobin and low-density lipoprotein
      cholesterol testing) and on hospitalization rates, controlling for patient
      characteristics. RESULTS: Patients with diabetes who saw P4P-participating
      physicians were more likely to receive quality care than those who did not (odds
      ratio, 1.16; 95% confidence interval, 1.11-1.22; P <.001). Patients with diabetes
      who received quality care were less likely to be hospitalized than those who did
      not (incident rate ratio, 0.80; 95% confidence interval, 0.80-0.85; P <.001).
      During 1 year, there was no difference in hospitalization rates between patients
      with diabetes who saw P4P-participating physicians versus those who did not.
      However, patients with diabetes who saw P4P-participating physicians in 3
      consecutive years were less likely to be hospitalized than those who did not
      (incident rate ratio, 0.75; 95% confidence interval, 0.61-0.93; P <.01).
      CONCLUSIONS: A P4P can significantly increase the receipt of quality care and
      decrease hospitalization rates among patients with diabetes in a PPO setting.
      Although it is possible that the differences observed between P4P-participating
      physicians and non-P4P-participating physicians were due to selection bias, we
      found no significant difference in the receipt of quality care between patients
      with diabetes who saw new P4P-participating physicians versus non-P4P
      participating physicians during the baseline year. Further research should focus
      on defining the effect of P4Ps on intermediate outcomes such as glycosylated
      hemoglobin and low-density lipoprotein cholesterol levels.

PMID- 20059288
TI  - Increasing copayments and adherence to diabetes, hypertension, and hyperlipidemic
      medications.
AB  - OBJECTIVE: To examine the impact of a medication copayment increase on adherence
      to diabetes, hypertension, and hyperlipidemic medications. STUDY DESIGN:
      Retrospective pre-post observational study. METHODS: This study compared
      medication adherence at 4 Veterans Affairs medical centers between veterans who
      were exempt from copayments and propensity-matched veterans who were not exempt.
      The diabetes sample included 1069 exempt veterans and 1069 nonexempt veterans,
      the hypertension sample included 3545 exempt veterans and 3545 nonexempt
      veterans, and the sample of veterans taking statins included 2029 exempt veterans
      and 2029 nonexempt veterans. The main outcome measure was medication adherence 12
      months before and 23 months after the copayment increase. Adherence differences
      were assessed in a difference-in-difference approach by using generalized
      estimating equations that controlled for time, copayment exemption, an
      interaction between time and copayment exemption, and patient demographics, site,
      and other factors. RESULTS: Adherence to all medications increased in the short
      term for all veterans, but then declined in the longer term (February-December
      2003). The change in adherence between the preperiod and the postperiod was
      significantly different for exempt and nonexempt veterans in all 3 cohorts, and
      nonadherence increased over time for veterans required to pay copayments. The
      impact of the copayment increase was particularly adverse for veterans with
      diabetes who were required to pay copayments. CONCLUSION: A $5 copayment increase
      (from $2 to $7) adversely impacted medication adherence for veterans subject to
      copayments taking oral hypoglycemic agents, antihypertensive medications, or
      statins.

PMID- 20059289
TI  - Non-quantal acetylcholine release at the neuromuscular junction.
AB  - There are two principal mechanisms of acetylcholine (ACh) release from the
      resting motor nerve terminal: quantal and non-quantal (NQR); the former being
      only a small fraction of the total, at least at rest. In the present article we
      summarize basic research about the NQR that is undoubtedly an important trophic
      factor during endplate development and in adult neuromuscular contacts. NQR helps
      to eliminate the polyneural innervation of developing muscle fibers, ensures
      higher excitability of the adult subsynaptic membrane by surplus polarization and
      protects the RMP from depolarization by regulating the NO cascade and chloride
      transport. It shortens the endplate potentials by promoting postsynaptic receptor
      desensitization when AChE is inhibited during anti-AChE poisoning. In adult
      synapses, it can also activate the electrogenic Na(+)/K(+)-pump, change the
      degree of synchronization of quanta released by the nerve stimulation and affects
      the contractility of skeletal muscles.

PMID- 20059290
TI  - Hyperoxia blunts acute hypoxia- and PGF2alpha-induced pulmonary vasoconstriction
      in chronically hypoxic rats.
AB  - We investigated the influence of oxygenation of in vitro lung preparation on the
      pulmonary vascular reactivity. Small pulmonary vessels isolated from adult male
      Wistar rats exposed for 4 days to hypoxia (F(iO2) = 0.1, group CH) were compared
      with those of normoxic controls (group N). The bath in the chamber of small
      vessel myograph was saturated with gas mixture containing either 21% or 95% of
      O(2) with 5% CO(2) and we measured the reactions of vessels to acute hypoxic
      challenge with 0% O(2) or to PGF(2alpha). We did not observe any difference of
      the contractile responses between both groups when the normoxic conditions were
      set in the bath. When the bath oxygenation was increased to 95% O(2), the
      contractions induced by hypoxic challenge and PGF(2alpha) decreased in
      chronically hypoxic rats and did not change in normoxic controls. We hypothesize
      that reduced reactivity of vessels from hypoxic rats in hyperoxia results from
      the effect of chronic hypoxia on Ca(2+) signaling in the vascular smooth muscle,
      which is modulated by increased free radical production during the exposure to
      chronic hypoxia and further hyperoxia.

PMID- 20059291
TI  - Effect of chronic nifedipine treatment on blood pressure and adrenergic responses
      of isolated mesenteric artery in young rats with developing spontaneous
      hypertension.
AB  - It is documented that in chronic hypertensive state there is an increased
      vasodepressor response to calcium channel antagonists such as the dihydropyridine
      derivate nifedipine. This effect is generally proportional to initial blood
      pressure as was demonstrated in several models of experimental hypertension. In
      the present study we investigated the effect of chronic nifedipine treatment on
      the development of cardiovascular system in young spontaneously hypertensive rats
      (SHR) in order to evaluate whether it could prevent the abnormalities leading to
      hypertensive state. Four- and eight-week-old rats were treated with nifedipine
      (50 mg/kg/day) for 4 weeks. Blood pressure of nifedipine-treated SHR remained at
      the initial level in contrast to their untreated controls where it continued to
      increase. In both age groups, chronic nifedipine administration reduced
      neurogenic contractions of isolated superior mesenteric artery, but did not
      significantly affect the dose-response curve to exogenous noradrenaline in 8-week
      old rats. In contrast, maximum response to noradrenaline was significantly
      attenuated in mesenteric artery of 12-week-old nifedipine-treated SHR. We can
      presume that the antihypertensive effect of nifedipine is similar in both stages
      of spontaneous hypertension development, but the mechanisms involved might be
      different. It seems that chronic reduction of calcium influx during the rapid
      phase of pathological blood pressure increase in SHR may eliminate the effect of
      enhanced sympathetic tone, which may have unfavorable consequences on
      cardiovascular structure and function.

PMID- 20059292
TI  - Age- and dose-specific anticonvulsant action of bumetanide in immature rats.
AB  - GABA exhibits depolarizing action in the immature neurons due to high
      intracellular activity of chloride ions. It is maintained by cation-chloride
      cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific
      inhibitor of this cotransporter. We studied possible anticonvulsant activity of
      bumetanide in pentylenetetrazol-induced seizures in three age groups of rat pups
      (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.)
      resulted in dose-dependent decrease of incidence of the tonic phase of
      generalized tonic-clonic seizures in 12-day-old rats only. No effect was observed
      in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not
      affect tonic convulsions but, on the contrary, decreased latencies of generalized
      seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably
      due to relative maturity of neurons in the brainstem where the generator of
      generalized seizures is localized. Age- and dose-specific suppression of the
      tonic phase needs further analysis.

PMID- 20059293
TI  - Modes of therapeutic engagement. Part I: diplomacy and integrity.
AB  - Our topic concerns strategies of therapeutic discourse, four relational modes of
      speaking and listening, adopted with and without awareness: diplomacy, integrity,
      sincerity, and authenticity. The four modes are offered as conceptual tools to
      help the therapist build therapeutic relationships, respond to challenges and
      impasses, and advance group process and insight. They are navigated to cement
      bonding, build trust, allow troubled relationships to evolve and resolve, and
      strengthen the abilities to think and relate. Presented in two separate articles,
      in Part I the topic and its relationship to truth and falsity is introduced, and
      the modes of diplomacy and integrity are described. The discussion continues, in
      Part II, where the focus is on sincerity and authenticity, and the
      interrelationship among the four modes and their differing functions in the
      totality of the clinical situation is illustrated.

PMID- 20059294
TI  - Models of therapeutic engagement. Part II: sincerity and authenticity.
AB  - Our topic concerns four relational modes of speaking and listening, and their
      relationship to truth and falsity. In a separate article, Part I introduced the
      topic and discussed the modes of diplomacy and integrity. The focus of Part II is
      on sincerity and authenticity, and on the interrelationship among all four modes
      and their differing functions in the totality of the clinical situation. Together
      the papers disentangle and address some of the technical issues that concern the
      relational group psychotherapist regarding topics of intersubjectivity,
      presentation of self, and self-disclosure. The four overlapping categories while
      nonexclusive are exhaustive; they supply conceptual references for the
      therapeutic stance one has adopted, allowing the therapist to be more aware of
      what he or she is doing and why.

PMID- 20059295
TI  - A decade of parent and infant relationship support group therapy programs.
AB  - A 10-year experience with a unique, short-term community group therapy program,
      Parent and Infant Relationship Support (PAIRS) for high risk infants and their
      parents is discussed. The program offers ten, 2-hour closed weekly group therapy
      sessions for mothers and their babies, following a parallel conjoint model of
      group work. The aims of the PAIRS group program are threefold: to increase
      positive parent-infant interaction and secure attachment, to decrease maternal
      postnatal depression, and to foster optimal infant development. Evaluation of the
      program has shown promising results in comparison with a control group. Clinical
      case material is used to illustrate therapeutic processes underlying the positive
      outcomes.

PMID- 20059296
TI  - Where intersubjectivity and group analysis meet.
AB  - Intersubjectivity can be defined as the union or contact of the subjectivities
      (Gordon, 1991). In therapy, it refers to the interaction between therapist and
      patient, and the processes that affect and are affected by that interaction. The
      essence of these interactions in the setting of group therapy, the obstacles that
      may arise because of them, and ways in which the therapist may identify and
      facilitate intersubjectivity in order to promote discourse that will enrich the
      sessions are discussed. I briefly touch upon earlier theories of psychoanalysis,
      demonstrating how changes in approaches influenced perceptions of what occurs in
      therapy. The unique place of intersubjectivity within the group analytic setting
      is emphasized using several vignettes from sessions I have led as a group analyst
      candidate to better illustrate how intersubjectivity can be observed in vivo.

PMID- 20059297
TI  - The codification and treatment of emotional abuse in structured group therapy.
AB  - Emotional abuse in childhood, in contrast to physical or sexual abuse, is a form
      of maltreatment which has been slow to receive widespread discussion.
      Categorizing emotional abuse highlights the ongoing realities of emotionally
      abused individuals. The five categories introduced here help to classify
      developmental problems, create treatment plans, and identify preventive
      opportunities. After a discussion of these categories, representative case
      histories from therapy groups are presented. These case histories are then traced
      through major phases of group therapy conducted within a structured setting and
      occurring on a time-limited basis.

PMID- 20059298
TI  - Group interpersonal psychotherapy for veterans with posttraumatic stress
      disorder: a pilot study.
AB  - Group-based interpersonal psychotherapy (IPT-G) was provided to nine male Vietnam
      veterans with posttraumatic stress disorder (PTSD) to reduce interpersonal
      difficulties. Standardized measures of posttraumatic stress, depression,
      interpersonal problems, and functioning were administered pre- and posttreatment
      and at 2- and 4-month follow-ups. Individual (reliable change indices) and group
      analyses (repeated measures ANOVAs) indicated improvements in interpersonal and
      global functioning (not maintained at follow-up), as well as for PTSD and
      depressive symptoms (maintained at follow-up). Qualitative feedback indicated
      reduced levels of anger and stress as well as improved relationships. IPT-G for
      Vietnam veterans shows promise in improving interpersonal functioning and
      reducing psychological distress. However, since not all improvements were
      maintained over time, future studies may need to explore relapse prevention
      strategies.

PMID- 20059299
TI  - Holding: a psychoanalytic commentary on Smith et al.,"A decade of parent and
      infant relationship support group therapy programs".

PMID- 20059300
TI  - Cohesion in cognitive-behavioral group therapy for anxiety disorders and major
      depression.

PMID- 20059301
TI  - In vitro cytotoxic activity of cationic paclitaxel nanoparticles on MDR-3T3
      cells.
AB  - Cationic paclitaxel nanoparticles were developed and the possible delivery
      mechanism was explored by cellular uptake studies. In vitro cytotoxicity of
      paclitaxel-loaded nanoparticles was evaluated with NIH-3T3 cells and multidrug
      resistant MDR-3T3 cells (with active P-glycoprotein). The IC(50)s of paclitaxel
      nanoparticles, liposomal paclitaxel, and Taxol((R)) on NIH-3T3 cells were 0.7
      microg/mL, 3.0 microg/mL, and 3.6 microg/mL, respectively, and on MDR-3T3 cells
      changed to 1.4 microg/mL, 4.4 microg/mL, and 7.3 microg/mL respectively. After
      addition of verapamil (nonspecific P-glycoprotein inhibition), the IC(50)s on MDR
      3T3 cells changed to 0.3 microg/mL, 0.7 microg/mL, and 1.5 microg/mL,
      respectively. The cellular uptake study of NBD-DOPE labeled nanoparticles by MDR
      3T3 cells showed more cellular associated fluorescence than neutral liposomes
      (EPC/cholesterol). The cellular uptake was not affected by verapamil. Fluorescent
      nanoparticle-encapsulated 10-nonyl bromide acridine orange also demonstrated an
      enhanced uptake compared to neutral liposomes. The cellular uptake was increased
      after verapamil's addition. The cellular uptake of formulations with increased
      positive charges and the competition of free cationic lipid GL89 demonstrated
      that the positive charge of the particles enhanced the cellular uptake. In
      conclusion, although the cationic paclitaxel nanoparticle is susceptible to P
      glycoprotein efflux, it is still a promising delivery system for paclitaxel,
      because of enhanced uptake, which resulted in significantly increased
      cytotoxicity.

PMID- 20059302
TI  - Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn
      contributes to reduced GABAergic tone and neuropathic pain after spinal cord
      injury.
AB  - Abstract In this study we explore if loss of GABAergic inhibitory interneurons in
      the superficial dorsal horn of the spinal cord contributes to reduced GABAergic
      tone and neuropathic pain following spinal cord injury (SCI). A moderate
      contusion injury to T11 resulted in the development of mechanical hyperalgesia
      and thermal hyperalgesia below the level of the lesion in gad1:GFP mice that were
      alleviated by IP administration of the GABA transporter antagonist tiagabine. Six
      weeks following SCI a decreased number of GFP(+) neurons were observed in the
      dorsal horn of SCI animals relative to sham mice. Tissue from a mouse 2 weeks
      post-SCI was subsequently observed to express activated caspase-3, indicative of
      apoptosis, co-localized to some GFP(+) GABAergic neurons. Glutamate decarboxylase
      (GAD)65 and GAD67 immunohistochemical staining was reduced in the dorsal horn of
      SCI animals. This observation was confirmed in Western blots showing reduced
      immunoreactivity for GAD67, as well as GABA transporter (GAT)1. Reversal of post
      SCI neuropathic pain by tiagabine suggests that reduced GABAergic tone may
      contribute to hyperalgesia symptoms. This is supported by the subsequent
      observation that SCI reduced the number of GFP(+) inhibitory neurons, and the
      finding that some GABAergic GFP(+) neurons undergo cell death at a time point
      consistent with the development of neuropathic pain following SCI. Concordantly,
      reductions in both GAD65 and GAD67 and GAT1 immunoreactivity also support the
      observation of a loss of GABAergic inhibition and the associated spinal
      interneurons.

PMID- 20059303
TI  - Hyperoxic reperfusion after global cerebral ischemia promotes inflammation and
      long-term hippocampal neuronal death.
AB  - In this study we tested the hypothesis that long-term neuropathological outcome
      is worsened by hyperoxic compared to normoxic reperfusion in a rat global
      cerebral ischemia model. Adult male rats were anesthetized and subjected to
      bilateral carotid arterial occlusion plus bleeding hypotension for 10 min. The
      rats were randomized to one of four protocols: ischemia/normoxia (21% oxygen for
      1 h), ischemia/hyperoxia (100% oxygen for 1 h), sham/normoxia, and
      sham/hyperoxia. Hippocampal CA1 neuronal survival and activation of microglia and
      astrocytes were measured in the hippocampi of the animals at 7 and 30 days post
      ischemia. Morris water maze testing of memory was performed on days 23-30.
      Compared to normoxic reperfusion, hyperoxic ventilation resulted in a significant
      decrease in normal-appearing neurons at 7 and 30 days, and increased activation
      of microglia and astrocytes at 7, but not at 30, days of reperfusion. Behavioral
      deficits were also observed following hyperoxic, but not normoxic, reperfusion.
      We conclude that early post-ischemic hyperoxic reperfusion is followed by greater
      hippocampal neuronal death and cellular inflammatory reactions compared to
      normoxic reperfusion. The results of these long-term outcome studies, taken
      together with previously published results from short-term experiments performed
      with large animals, support the hypothesis that neurological outcome can be
      improved by avoiding hyperoxic resuscitation after global cerebral ischemia such
      as that which accompanies cardiac arrest.

PMID- 20059305
TI  - Wavelet based R-peak detection for heart rate variability studies.
AB  - Detection of QRS complex in electrocardiogram (ECG) signals is of immense
      importance in cardiac health prognosis. In this paper a new symmetric wavelet for
      detection of R-peak is presented, which has been designed based on spectral
      characteristics and morphology of QRS complex. The detection of R-peak was
      carried out using this designed wavelet, and with existing symmetric wavelets
      such as db3, db6, haar and bior2.2. The detection accuracy with this wavelet is
      99.99%, which is higher than those with existing symmetric wavelets. The
      algorithm has been tested on standard databases such as Fantasia database of
      normal and healthy subjects, MIT/BIH (Massachusetts Institute of Technology/Beth
      Israel Hospital) arrhythmia database, and on self-recorded electrocardiograms of
      normal subjects and patients under diseased stress. The study of heart rate
      variability (HRV) through computation of RR-tachogram using the new wavelet has
      proved to be effective in reliably evaluating HRV parameters.

PMID- 20059304
TI  - A cross-sectional study on the shift work and metabolic syndrome in Japanese male
      workers.
AB  - INTRODUCTION: Shift work has been reported to be associated with an increase in
      the metabolic syndrome (MetS). To clarify the association between the type of
      shift work and the risk of MetS, a cross-sectional field survey was conducted
      after adjusting for age and lifestyle factors. METHODS: The subjects were 3007
      Japanese males, aged 34-64 years old, who were employees (1700 day and 1307 shift
      workers) of a car-manufacturing company. The standard Japanese criteria for the
      diagnosis of MetS was used. Age, smoking habit, drinking habit, sleeping habit
      and exercise habit were used as the independent variables. RESULTS: The
      prevalence of MetS in the day workers, two-shift workers, and three-shift workers
      were 13.8% (234/1700), 10.7% (120/1125) and 17.6% (32/182), respectively. There
      was a significant difference in the prevalence between the two-shift workers and
      the day workers. Estimation of the odds ratios (95% confidence intervals) of age,
      two-shift work and habitual exercise for MetS were 1.03 (1.01-1.04), 0.77 (0.61
      0.98) and 0.64 (0.51-0.81), respectively. CONCLUSION: Two-shift work was
      associated with lower risk of MetS, which is not in accordance with past reports.
      This finding should therefore be re-analysed, including investigation of the job
      content in each group.

PMID- 20059306
TI  - Effect of position of electrodes relative to the innervation zone onsurface EMG.
AB  - We investigated the effect of the position of electrodes relative to the
      innervation zone (IZ) of the biceps brachii muscle during isometric elbow flexion
      using eight-channel surface array electrodes. We estimated the location of the IZ
      near the centre of the muscle in 20 male subjects. The pulse peaks from
      electromyogram (EMG) waveforms were detected for each channel and averaged, the
      triphasic pulse was determined, and the peak values of the first and third phases
      were compared. The results showed significantly greater pulse values for the
      first phase when the electrode placement was proximal to the estimated IZ, and
      for the third phase when the electrode placement was distal to the estimated IZ.
      Using this method, the positional relationship between electrodes and IZ can be
      determined using a surface EMG waveform recorded with a pair of bipolar
      electrodes. This method may be clinically useful in confirming the reliability of
      a recorded surface EMG.

PMID- 20059307
TI  - Depressive disorders among adolescents managed in a child and adolescent mental
      health service.
AB  - OBJECTIVE: The aims were to describe the prevalence and treatment of depressive
      disorders among case-managed adolescents attending a regional Child and
      Adolescent Mental Health Service (CAMHS). METHOD: An observational study was
      conducted in a regional CAMHS over a 3-month period. Clinicians recorded
      treatment of their case-managed adolescents aged 12-18 years at the end of each
      calendar month. The Health of the Nation Outcome Scale for Children and
      Adolescents (HoNOSCA) and Children's Global Assessment Scale (CGAS) were
      collected at the beginning of the study period or at entry into the service, and
      repeated at discharge from the service or at the conclusion of the study period.
      Adolescents also completed the Reynold's Adolescent Depression Scale, 2nd
      edition. RESULTS: Depressive disorders were the most common clinician diagnosis
      reported (22%). There was no statistically significant difference in treatment
      for depressed compared to non-depressed adolescents. There was a statistically
      significant improvement in both the HoNOSCA scores (p <0.001) and CGAS scores (p
      <0.001) for the whole sample. CONCLUSION: Treatment appeared to be the same in
      type for depressed compared to non-depressed adolescents case managed within
      CAMHS.

PMID- 20059308
TI  - Consultation-liaison psychiatry in a maternity hospital.
AB  - OBJECTIVE: The aim of the study was to describe referral patterns of maternity
      inpatients to the consultation-liaison psychiatry (CLP) service at a large
      women's hospital in metropolitan Melbourne, Australia. METHOD: Clinicians
      recorded socio-demographic data, referring unit, consultee's reason for referral,
      psychiatric diagnosis made, and treatment provided for all maternity inpatients
      referred from 2004 to 2008. RESULTS: Main reasons for referral were detection of
      depression, past psychiatric history, and concern regarding a woman's coping.
      Most common diagnoses were depression, substance use disorders and anxiety
      disorders. Many women referred for assessment while inpatients were initially
      seen in the antenatal period. CONCLUSIONS: Pregnant women referred to a CLP
      service present with a range of mental health problems, most often depression,
      anxiety and substance use disorders. Many of these problems are evident in and
      require intervention during the antenatal period as well as at the time of
      confinement. CLP services to maternity hospitals should be provided in the
      antenatal as well as the inpatient setting.

PMID- 20059309
TI  - Antiretroviral prescribing patterns in treatment-naive patients in the United
      States.
AB  - Numerous antiretroviral therapy (ART) regimens are recommended for first-line and
      subsequent HIV care, but regimen selection for clinical use may not represent the
      full range of options. We hypothesized that despite an increase in available
      antiretrovirals, clinical trial data on regimen efficacy and fixed-dose
      combination options have lead to uniformity in initial ART. We evaluated regimen
      selection for ART-naive patients at the University of Alabama at Birmingham (UAB)
      1917 Clinic between January 2000 and December 2007. The annual number of unique
      initial regimens was quantified. Initial regimen variability was expressed as
      regimens per 100 patients. Subsequent ART regimens were characterized for
      complexity via regimen sequence trees detailing the first three generations of
      regimens for patients starting the two most common initial combinations. Four
      hundred eighty-two ART-naive patients were treated with 39 unique initial
      regimens (8.0 regimens per 100 patients). Variability in initial regimen
      selection was highest in the first 6 years (14.9-24.4 regimens per 100 patients).
      A sharp decline was observed in 2006 (16.1 regimens per 100 patients) and 2007
      (6.5 regimens per 100 patients). The most dramatic shift in drug selection
      involved an increase in emtricitabine plus tenofovir plus efavirenz, from 0% in
      2003 to 85% in 2007. During the study period, 205 of 482 (43%) patients required
      a change in initial therapy. Of these, 156 of 205 (76%) had a unique sequence of
      regimens. A shift toward homogeneity of initial ART was observed (85% of patients
      received the same first-line regimen in 2007). In contrast, regimen sequencing
      beyond the first regimen remained complex. These shifts in ART prescribing
      patterns may have implications for collaborative HIV care.

PMID- 20059310
TI  - Gene-Eden, a broad range, natural antiviral supplement, may shrink tumors and
      strengthen the immune system.

PMID- 20059311
TI  - Pancreatic cancer: progress made.
AB  - Pancreatic cancer remains a deadly disease. Despite advances on many fronts,
      surgeons play a leading role in the diagnosis and management of pancreatic
      cancer. Preoperative staging is best provided by "pancreas-protocol" abdominal
      CT, although endoscopic ultrasound and diagnostic laparoscopy can add value in
      selected patients. Surgical resection, which remains the only curative option, is
      now accomplished with uniformly low perioperative mortality in high-volume
      centers (<3%), although complications remain frequent. Unfortunately, the long
      term prognosis for pancreatic cancer remains poor with 5-year survival rates only
      15-23% with median survival of 13 to 18 months. Recent data from randomized
      trials have supported the role for adjuvant chemotherapy and questioned the
      traditional role of radiation. Early diagnosis and targeted multimodality
      treatments would appear essential to optimizing the results of surgical therapy.

PMID- 20059312
TI  - Disregarding clinical trial-based patient-reported outcomes is unwarranted: Five
      advances to substantiate the scientific stringency of quality-of-life
      measurement.
AB  - BACKGROUND: The clinical impact of trial-based quality of life (QL) outcomes is
      frequently underestimated due, in part, to prejudice and lack of knowledge by the
      medical community. The objectives of this paper are to show that QL assessments
      build upon an empirically based and stringent approach to measurement and QL
      outcomes should not be viewed nor handled differently than any other parameter in
      medical research. MATERIAL AND METHODS: Literature overview. RESULTS: The
      objectives are substantiated with empirical evidence showing that: (1) existing
      QL measures are as reliable as most other clinical outcomes; (2) available
      guidelines improve the quality of trial-based QL data; (3) QL data have strong
      prognostic value for survival; (4) clinical significance of QL data can be
      established; and (5) accounting for response-shift effects in QL data over time
      is feasible. Finally, the investigation of the genetic disposition of QL is
      described as an emerging area of research. DISCUSSION: It is a waste of effort
      and money and also unethical when collected trial-based QL data are not used to
      their full power. QL and other patient-reported outcomes deserve to be included
      in more trials, with full disclosure of all results, and standardized
      interpretation. Only the combined use of patient-reported and clinical outcomes
      will enable the examination of the extent to which cancer patients live a
      qualitatively good life as long as possible.

PMID- 20059313
TI  - Ensuring quality in studies linking cancer registries and biobanks.
AB  - The Nordic countries have a long tradition of providing comparable and high
      quality cancer data through the national population-based cancer registries and
      the capability to link the diverse large-scale biobanks currently in operation.
      The joining of these two infrastructural resources can provide a study base for
      large-scale studies of etiology, treatment and early detection of cancer.
      Research projects based on combined data from cancer registries and biobanks
      provides great opportunities, but also presents major challenges. Biorepositories
      have become an important resource in molecular epidemiology, and the increased
      interest in performing etiological, clinical and gene-environment-interaction
      studies, involving information from biological samples linked to population-based
      cancer registries, warrants a joint evaluation of the quality aspects of the two
      resources, as well as an assessment of whether the resources can be successfully
      combined into a high quality study. While the quality of biospecimen handling and
      analysis is commonly considered in different studies, the logistics of data
      handling including the linkage of the biobank with the cancer registry is an
      overlooked aspect of a biobank-based study. It is thus the aim of this paper to
      describe recommendations on data handling, in particular the linkage of biobank
      material to cancer registry data and the quality aspects thereof, based on the
      experience of Nordic collaborative projects combining data from cancer registries
      and biobanks. We propose a standard documentation with respect to the following
      topics: the quality control aspects of cancer registration, the identification of
      cases and controls, the identification and use of data confounders, the stability
      of serum components, historical storage conditions, aliquoting history, the
      number of freeze/thaw cycles and available volumes.

PMID- 20059314
TI  - Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary
      metastases from malignant melanoma.
AB  - OBJECTIVES: Most guidelines consider FDG PET-CT to detect occult extra-pulmonary
      disease prior to lung metastasectomy. A cost-effectiveness analysis, using a
      Markov model over a 10 year period, was performed to compare two different
      surveillance programs, either PET-CT or whole-body CT, in patients with suspected
      pulmonary metastasised melanoma. METHODS: Data from published studies provided
      probabilities for the model. Complication and care costs were obtained from
      standardised administrative databases from 19 hospitals identified by DRG codes
      (reported in 2009 Euros). For the cost calculation of PET-CT we performed a
      microcosting analysis. All costs and benefits were yearly discounted at
      respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the
      number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per
      LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in
      all model parameters. RESULTS: The PET-CT strategy provided 86.29 LMG (95% CI:
      81.50-90.88 LMG) at a discounted cost of euro3,974 (95% CI: euro1,339-12,303),
      while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a
      discounted cost of euro5,022 (95% CI: euro1,378-16,018). This PET-CT strategy
      resulted in a net saving of euro1,048 with a gain of 0.2 LMG. Based on PET-CT
      findings, 20% of futile surgeries could be avoided. CONCLUSION: Integrating PET
      CT in the management of patients with high risk MM appears to be less costly and
      more accurate by avoiding futile thoracotomies in one of five patients as well as
      by providing a small survival benefit at 10 years.

PMID- 20059315
TI  - The 10-23 DNA enzyme generated by a novel expression vector mediate inhibition of
      taco expression in macrophage.
AB  - The 10-23 DNA enzyme (10-23 DNAzyme), a single-stranded DNA (ssDNA) molecule, can
      efficiently and specifically cleave almost any target RNA molecules. Therefore,
      it is regarded as one of the promising tools in gene therapy. However, there are
      still some obstacles, such as low efficiency of cellular uptake and instability
      in vivo, in its application. Taking advantage of the mechanism of Moloney mouse
      leukemia virus (MMLV) reverse transcriptase (RT), we investigate the construction
      of a novel ssDNA expression vector in this study. In order to improve the
      expression efficiency, the mmlv-rt gene and ODN-PMT (an oligodeoxynucleotide
      including other essential sequences for generating ssDNA) were cloned into a
      single plasmid under the control of 2 separated promoters. The ability of the
      vector to generate specific 10-23 DNAzyme in mammalian cell was tested by
      constructing a tryptophan-aspartate-containing coat protein (taco) gene-specific
      10-23 DNAzyme expression plasmid. The potential of the expressed 10-23 DNAzyme to
      suppress TACO expression was also investigated. Our results indicated that this
      vector generates desired 10-23 DNAzyme in mammalian cells. The expressed 10-23
      DNAzyme targeting taco gene can reduce TACO expression both at mRNA level (by
      78.26%) and at protein level (by 75.30%).

PMID- 20059316
TI  - Influenza A viruses in wild birds of the Pacific flyway, 2005-2008.
AB  - Avian influenza viruses (AIVs) pose a significant threat to public health, and
      viral subtypes circulating in natural avian reservoirs can contribute to the
      emergence of pathogenic influenza viruses in humans. We investigated the
      prevalence and distribution of AIVs in 8826 migratory and resident wild birds in
      North America along the Pacific flyway, which is a major north-south migration
      pathway that overlaps with four other flyways in Alaska providing opportunities
      for mixing of Eurasian and American origin influenza viruses. Overall, the
      prevalence of AIVs was low (1%) among the wide range of avian species tested, but
      we detected AIVs in 69 hunter-harvested waterfowl (Anseriformes) sampled at a
      national wildlife refuge in California from October 2007 to January 2008. A wide
      range of subtypes were detected in waterfowl with H6N1, H10N7, H7N3, and H3N5
      being the most common. We suspect H6N1 was introduced or remerged in 2007 at this
      key wintering site for waterfowl along the Pacific Flyway. Over a 3-week period,
      13 H6N1 AIVs were isolated from two northern pintails (Anas acuta), three
      northern shovelers (Anas clypeata), three ring-necked ducks (Aythya collaris),
      four American widgeon (Anas americana), and one gadwall (Anas strepera). We
      conclude that a diverse array of AIVs was present and that cross-species
      transmission was occurring among waterfowl in the central valley wetlands of
      California.

PMID- 20059317
TI  - Molecular detection of Bartonella alsatica in European wild rabbits (Oryctolagus
      cuniculus) in Andalusia (Spain).
AB  - A sample of 279 European wild rabbits, Oryctolagus cuniculus (141 males, 138
      females), captured alive in Andalusia (Spain) and belonging to the two haplotype
      classes previously described for this species (230 and 49 corresponding with
      haplotypes A and B, respectively), were tested for the presence of Bartonella
      alsatica DNA. Two species-specific nested polymerase chain reaction assays
      targeting for 16S-23S rRNA intergenic spacer region and RNA polymerase beta
      subunit genes have been developed. Forty-eight (17.20%) rabbits were infected
      with B. alsatica. Two-way contingency table analyses and the calculation of
      Cramer's V statistic showed no differences in infection rate, considering
      haplotype lineage or sex. The risk of infection of human population, especially
      for hunters in close contact with this demonstrated human pathogen, should be
      considered.

PMID- 20059318
TI  - Effects of temperature and rainfall on the activity and dynamics of host-seeking
      Aedes albopictus females in northern Italy.
AB  - The Asian tiger mosquito, Aedes albopictus, has colonized nearly all the regions
      of Italy as well as other areas of Europe. During the summer of 2007 the tiger
      mosquito was responsible for an outbreak of Chikungunya in Italy, when this virus
      was brought in by a tourist of Indian origin returning from an endemic area. To
      increase the knowledge of tiger mosquito population dynamics, a survey was
      carried out from April to November 2008 in the municipalities of Arco and Riva
      del Garda (northern Italy) through a Biogents SentinelTM (BG)-trap sampling. In
      particular, the aim of the study was to evaluate the influence of temperature and
      rainfall on the activity and dynamics of A. albopictus host-seeking females. The
      seasonal emergence of host-seeking females was strongly influenced by the minimum
      temperature, and a lower threshold of 13 degrees C was identified. In addition,
      the threshold for the end of adult activity was found at a minimum temperature of
      9 degrees C. Host-seeking female abundance was positively affected by the
      accumulated temperatures over the period 3 and 4 weeks before the sampling week,
      possibly as a consequence of the positive effect of accumulated temperatures on
      larval density. Instead, accumulated precipitation over 1-4 weeks before sampling
      was negatively correlated with host-seeking female abundance. Finally, the
      activity of host-seeking females, estimated by the weekly increment in female
      abundance, was positively affected by the total abundance of females and by mean
      weekly temperatures. Our study provides useful information for predicting the
      dynamics of host-seeking Ae. albopictus females in northern Italy and for
      designing control strategies for preventing arbovirus outbreaks in areas
      colonized by Ae. albopictus.

PMID- 20059319
TI  - Using a neodymium magnet to target delivery of ferumoxide-labeled human neural
      stem cells in a rat model of focal cerebral ischemia.
AB  - Efficiency of targeted delivery of stem cells via transplantation by intravenous
      injection is limited because of rapid clearance. Thus, more effective, newer
      methods are required. We hypothesized that combining the use of ferumoxide
      labeling and magnetic fields could enhance targeted delivery of stem cells. The
      effects of a magnetic field on proliferation, viability, and differentiation of
      human neural stem cells (NSCs) were determined in culture, and the results
      indicated that the difference between control and cultures exposed to a magnetic
      field were insignificant. To assess migration in vitro, ferumoxide-labeled cells
      were seeded into a culture dish that had a neodymium magnet below its center, and
      the labeled NSCs were found to aggregate above the magnet. To investigate
      targeted delivery of NSCs in vivo, rats were separated into three groups:
      ischemia only (IO), ischemia with injection of ferumoxide-labeled cells (IC), and
      ischemia with injection of labeled cells and magnet exposure (ICM). Twenty-four
      hours after middle cerebral artery occlusion (MCAo), labeled human NSCs were
      injected into the tail vein. Seven days after MCAo, ICM rats had a larger number
      and greater distribution of Prussian blue-positive NSCs as compared with
      controls. In addition, infarct volume in ICM rats was significantly reduced. Our
      study suggests that this use of a magnetic field may be useful for improving the
      efficacy of targeted migration of stem cells in stem-based cell therapy in
      ischemic brain injury.

PMID- 20059320
TI  - Ergonomics, surgeon comfort, and theater checklists in pediatric laparoscopy.
AB  - Laparoscopy is often carried out with personnel unfamiliar with the equipment and
      layout, thereby forcing the surgical team to adapt by twisting and stretching
      awkwardly. This can make laparoscopy more difficult and frustrating for the
      surgeon, potentially increasing patient risk. We carried out a short survey of
      laparoscopic procedures to determine when surgeons experience discomfort, and
      whether or not operative checklists could reduce these. MATERIALS AND METHODS:
      All patients undergoing laparoscopic operations by one surgeon between November
      2006 and May 2007 were studied. Patients and surgeons had various physical
      measurements recorded, including the placement and orientation of equipment,
      staff and patients, any problems arising, and the discomfort of the surgical
      team. Scaled diagrams were drawn, outlining positions and orientation, allowing
      the measurement of the degree to which the surgeons twisted and stretched.
      Peroperative surgeon comfort levels were recorded. The ideal table height for
      surgery was calculated, suggestions to improve the surgeon's comfort were
      identified, recommendations on theater layout were produced, and sample
      checklists of common problems with ways of avoiding them were established.
      RESULTS: Of 31 procedures, 10 had full data recorded for analysis. Physically
      demanding positions were common. There was no correlation between surgeon
      position and comfort for short operations (<60 minutes). Data for operative time
      >60 minutes was incomplete, but a definite trend to increasing discomfort with
      time was evident. In 10 operations, 85 problems occurred, 57 relating to theater
      layout. A third were avoidable repeat problems. CONCLUSIONS: Simple measurements
      of surgeons, patients, and equipment improves staff and equipment positioning. A
      log of problems and discomforts in the theater ensures that preventable factors
      are not repeated, reducing the frustrations of laparoscopy. By planning equipment
      positioning and testing it, a preferred theater set-up layout can be retained for
      future use. Checklists would help in the smooth execution of a laparoscopic
      procedure.

PMID- 20059321
TI  - Carbondioxide pneumoperitoneum prevents postoperative adhesion formation in a rat
      cecal abrasion model.
AB  - PURPOSE: We aimed to investigate the role of the carbon-dioxide (CO(2))
      pneumoperitoneum on the prevention of postoperative adhesion formation. METHODS:
      Thirty adult male Sprague-Dawley rats (250-350 g) were used for this study. The
      rats were randomly divided into three groups; in the sham group (n = 10) only,
      laparotomy was made, in group 2 (n = 10), a pneumoperitoneum was applied for a
      half-hour duration, followed by laparatomy, and in group 3 (n = 10),
      pneumoperitoenum time was 2 hours and after a pneumoperitoneum laparotomy was
      made. A cecal abrasion model was studied for making an adhesion formation. On day
      14, all rats were sacrificed and adhesions were scored. Tissue samples from
      adhesions and peritonea and the cecum wall were examined, both pathologically and
      biochemically, for tissue hydroxyproline content. RESULTS: There was a
      statistically significant difference between the control and pneumoperitoneum
      groups, regarding adhesion numbers and grades (P < 0.001). Cecal tissue
      hydroxypyroline content level was lower in group 1, and statistically significant
      differences were observed between groups 1, 2, and 3 regarding hydroxyproline
      content (P < 0.001). There was a statistically significant difference between the
      control and pneumoperitoneum groups regarding inflammation (P = 0.002).
      CONCLUSIONS: Pretreatment with the CO(2) pneumoperitoneum had a prophylactic
      effect on postoperative adhesion formation in this study.

PMID- 20059322
TI  - Half-Pringle maneuver: a useful tool in laparoscopic liver resection.
AB  - INTRODUCTION: Laparoscopic liver resections are becoming a common procedure, and
      bleeding remains the major concern during parenchymal transection. Total vascular
      inflow occlusion can be performed, but ischemic reperfusion injuries can lead to
      postoperative morbidity. On the other hand, hemihepatic inflow occlusion, leading
      to hemiliver ischemia, decreases the amount of liver parenchyma submitted to
      reperfusion damage and offers the advantage of reduced blood loss. OBJECTIVE: The
      aim of this work was to describe our experience with laparoscopic the half
      Pringle maneuver for segmentar or nonanatomic liver resctions. PATIENTS AND
      METHODS: Eight patients submitted to laparoscopic liver resection in a single
      tertiary center. RESULTS: There were 5 women and 3 men with a mean age of 40.2
      years (range, 26-54). Mean tumor size was 4.1 cm (range, 2.6-6.0), and mean
      hospital stay was 3.1 days (1-5). There were 3 liver adenomas, 2 hepatocellular
      carcinomas, 1 metastatic melanoma, 1 metastatic colorectal carcinoma, and 1
      peripheral colangiocarcinoma. No postoperative complications or mortalities were
      observed. CONCLUSIONS: Results demonstrate that laparoscopic liver resection with
      the half-Pringle maneuver is feasible and safe and may be included in the
      technical armamentarium of laparoscopic liver resections for a selected group of
      patients.

PMID- 20059323
TI  - Multidisciplinary care of occipital arteriovenous malformations: effect on
      nonhemorrhagic headache, vision, and outcome in a series of 135 patients.
      Clinical article.
AB  - OBJECT: In this study, the authors evaluated how an appropriate allocation of
      patients with occipital arteriovenous malformations (AVMs) who were treated
      according to different strategies would affect nonhemorrhagic headache, visual
      function, and hemorrhage risk levels. METHODS: Of the 712 patients with brain
      AVMs in the Toronto Western Hospital prospective database, 135 had occipital
      AVMs. The treatment decision was based on patients' characteristics,
      presentation, and morphology of the AVM. The management modalities were
      correlated with their outcomes. RESULTS: The mean follow-up period was 6.78
      years. Nonhemorrhagic headache was the most frequent symptom (82 [61%] of 135
      patients). Ninety-four patients underwent treatment with one or a combination of
      embolization, surgery, or radiosurgery, and 41 were simply observed. Of the 40
      nontreated patients with nonhemorrhagic headache, only 12 (30%) showed
      improvement. In the observation group 2 patients (22%) had worsening of visual
      symptoms, and 2 experienced hemorrhage, for an annual hemorrhage rate of 0.7% per
      year; 1 patient died. In the treatment group, the improvement in nonhemorrhagic
      headache in 35 patients (83%) was significant (p < 0.0001). Visual deficit at
      presentation worsened in 2 (8%), and there were 8 new visual field deficits (9%).
      The visual worsening was not significantly different. There were 2 other
      neurological deficits (2%) and 2 deaths (2%) related to the AVM treatment. One
      AVM hemorrhaged. The annual hemorrhage rate was 0.1% per year. The hemorrhage
      risk in the observation and treatment groups was lower than the observed
      hemorrhage risk of all patients with AVMs (4.6%) at the authors' institution.
      CONCLUSIONS: Appropriate selection of patients with occipital AVMs for one or a
      combination of treatment modalities yields a significant decrease in
      nonhemorrhagic headache without significant visual worsening. The
      multidisciplinary care of occipital AVMs can aim for an apparent decrease in
      hemorrhage risk.

PMID- 20059324
TI  - Comparison of dismembered and nondismembered Y-V laparoscopic pyeloplasty in
      patients with primary hydronephrosis.
AB  - INTRODUCTION: A retrospective study was performed to compare the results of
      dismembered and nondismembered Y-V laparoscopic pyeloplasties and the
      complications observed after the two types of surgery. MATERIALS AND METHODS:
      Eighty-eight patients with ureteropelvic junction obstruction (UPJO) underwent a
      laparoscopic operation. In 2 cases, an open conversion was made. A laparoscopic
      Hynes-Anderson pyeloplasty (LH-AP) was performed on 50 patients, whereas a
      laparoscopic Y-V pyeloplasty (LY-VP) was performed in 36 cases. The diagnosis of
      UPJO was based on a complete medical history, ultrasonography, diuretic urography
      (IVU), and/or diuretic renography. The mean follow-up was 29 (range, 6-66)
      months. Complete success was defined as the absence of any clinical symptoms,
      combined with a significant reduction of hydronephrosis on IVU and
      ultrasonography, as well as no sign of obstruction on IVU and/or diuretic
      renography. RESULTS: The mean operative time for LH-AP was 219 minutes and for LY
      VP 185 minutes. The mean hospital stay after LH-AP was 5.9 days and after LY-VP
      5.3 days. The overall success rate was 91.5% (91.8% for LH-AP patients and 91.2%
      for LY-VP patients). CONCLUSION: LY-VP appears to be a safe, attractive
      alternative to LH-AP.

PMID- 20059325
TI  - Modified laparoscopic abdominal vesico-vaginal fistula repair--"Mini-O'Conor"
      vesicotomy.
AB  - AIM: The aim of this work was to report on our experience with the laparoscopic
      repair of vesicovaginal fistulae and describe a modification in technique.
      PATIENTS AND METHODS: Between 2004 and 2008, 8 patients underwent laparoscopic
      repair of vesicovaginal fistula. All patients had fistulae secondary to
      gynecologic surgery. Two patients had undergone previous failed attempts at
      repair. The mean interval prior to repair was 3.5 months. Patient underwent
      repair by using a limited cystotomy. RESULTS: The operation was successfully
      completed in all cases. Mean operative time was 145 minutes, and mean estimated
      blood loss 60 mL. There were no complications. Catheter removal was done at 14
      days. All patients were continent after catheter removal and remained continent
      at a mean follow-up of 29 months. CONCLUSION: Laparoscopic repair of
      vesicovaginal fistula is safe and effective. Bivalving of the bladder may be
      avoided by use of a small cystotomy, with the potential benefits of shorter
      operative time and reduced bladder spasms.

PMID- 20059326
TI  - Surgical management of ovarian disease in infants, children, and adolescents: a
      15-year review.
AB  - BACKGROUND: Despite the reported efficacy and the presumed benefits of minimally
      invasive surgery (MIS) for ovarian lesions in adults, questions remain as to the
      surgical indications, results, and outcomes for these procedures across pediatric
      age groups. The aim of this study was to review our experience with the
      management of ovarian disease in children to determine if there has been a shift
      in the management of these lesions from open surgery (OS) to an MIS approach in
      the pediatric population. METHODS: An institutional review board (IRB)-approved
      retrospective chart review included all patients who underwent surgical
      management of ovarian disease from January 1, 1992 to July 10, 2007. Patients
      with ectopic pregnancy, known pelvic inflammatory disease, or concomitant illness
      requiring operative management at the time of ovarian surgery were excluded.
      Demographics, clinical signs and symptoms, diagnosis, surgical outcomes, and
      history of prior abdominal procedures were obtained. Statistical analysis
      included comparison of means, paired t-test, chi-squared test, and multivariate
      analysis, where indicated. RESULTS: A total of 231 patients were evaluated in
      this study, with a mean age of 12.8 years (range, 3 weeks to 20 years). There
      were 221 (95.7%) benign lesions and 10 (4.3%) were malignant. There were 156
      simple or hemorrhagic cysts (70.5%) and 46 mature teratomas (20.8%). Three
      complications (1.3%) occurred, which were associated with surgery and no
      mortalities. Abdominal pain (82.3%), nausea or vomiting (24.2%), and abdominal
      tenderness (10.0%) were the most common presenting symptoms or signs. Operative
      outcomes for benign disease (n = 221) were compared between MIS and open cases
      over the entire time period as well as within three consecutive 5-year time
      intervals. CONCLUSIONS: There was a notable shift toward the management of benign
      ovarian disease in using MIS techniques over the course of three different 5-year
      intervals. This approach was also associated with shorter hospital stay, less
      operative blood loss, and shorter operative times, when compared to an open
      approach. When indicated, a laparoscopic approach should be performed for
      presumed benign ovarian disease in children.

PMID- 20059327
TI  - Eliminating the effects of paradoxic imaging during laparoscopic surgery.
AB  - BACKGROUND: Complex laparoscopic tasks are nearly impossible to complete when the
      telescope is pointed toward the operator (i.e., paradoxic image). Attempts at
      image manipulation have been reported, but altered monitor displays may introduce
      even more confusion. The availability of high-quality, lightweight, head-mounted
      displays (HMDs) now allows individualization of the laparoscopic image. We
      studied the effect of manipulation of the paradoxic image on task performance.
      STUDY DESIGN: Fifteen surgical residents (PGY levels 1-5) were timed while
      performing the standard "bead pass" skill from the Fundamentals of Laparoscopic
      Surgery (FLS) course. Conventional diamond-shaped configuration, with telescope
      and camera in line with the operator and overhead image projection at the
      opposite end, served as control. A paradoxic image was created by placing the
      telescope at the opposite side of the box trainer (180 degrees from operator),
      and the task was repeated with different image corrections: (1) paradoxic image
      as-is; (2) left-right reversed image (mirror); and (3) left-right reversed and
      upside-down image (i.e., inverted mirror). Times were recorded and analyzed for
      intra- and interoperator variance and compared with control. RESULTS: Time-per
      bead was 7.5 +/- 1.5 seconds (standard error of the mean) in controls. With the
      as-is paradoxic image, time-per-bead was 164.1 +/- 80.8 seconds/bead. All but 2
      residents failed to complete the task. Times were 120.0 +/- 55.9 seconds/bead for
      the mirror image and 46.7 +/- 26.0 seconds/bead for the inverted mirror image (P
      < 0.01; ANOVA and Kruskal-Wallis). CONCLUSIONS: The difficulty of performing a
      relatively simple laparoscopic task with paradoxic image display was almost
      insurmountable. Left-right image inversion was not sufficient to correct the
      handicap. Inverted mirror-image projection significantly improved performance,
      which almost reached control levels. The availability of personal image-display
      devices may, in the future, allow image customization for task performance in
      suboptimal conditions during endoscopic surgery.

PMID- 20059328
TI  - The utility of evolving simulated robot morphology increases with task complexity
      for object manipulation.
AB  - Embodied artificial intelligence argues that the body and brain play equally
      important roles in the generation of adaptive behavior. An increasingly common
      approach therefore is to evolve an agent's morphology along with its control in
      the hope that evolution will find a good coupled system. In order for embodied
      artificial intelligence to gain credibility within the robotics and cognitive
      science communities, however, it is necessary to amass evidence not only for how
      to co-optimize morphology and control of adaptive machines, but why. This work
      provides two new lines of evidence for why this co-optimization is useful: Here
      we show that for an object manipulation task in which a simulated robot must
      accomplish one, two, or three objectives simultaneously, subjugating more aspects
      of the robot's morphology to selective pressure allows for the evolution of
      better robots as the number of objectives increases. In addition, for robots that
      successfully evolved to accomplish all of their objectives, those composed of
      evolved rather than fixed morphologies generalized better to previously unseen
      environmental conditions.

PMID- 20059330
TI  - Emotion recollected in tranquility: lessons learned from the COX-2 saga.
AB  - Nonsteroidal antinflammatory drugs (NSAIDs) inhibit prostaglandin formation by
      cyclooxygenases (COX) 1 and 2. NSAIDs selective for inhibition of COX-2 are less
      likely than traditional drugs to cause serious gastrointestinal adverse effects,
      but predispose to adverse cardiovascular events, such as heart failure,
      myocardial infarction, and stroke. Evidence from human pharmacology and genetics,
      genetically manipulated rodents, and other animal models and randomized trials
      indicates that this is consequent to suppression of COX-2-dependent
      cardioprotective prostagladins, particularly prostacyclin. Lessons drawn from how
      this saga unfolded are relevant to how we approach drug surveillance and
      regulation, integrate diversifed forms of information and might pursue a more
      personalized approach to drug efficacy and risk.

PMID- 20059331
TI  - The future of antiplatelet therapy in cardiovascular disease.
AB  - Mechanisms of platelet inhibition are reviewed with emphasis on the
      pharmacokinetic and pharmacodynamic determinants of clinical efficacy and safety
      of antiplatelet drugs. Current developments in antiplatelet therapy are discussed
      in relation to both primary and secondary prevention of atherothrombotic
      complications. Interindividual variability in response to antiplatelet agents and
      new drug targets are outlined within the context of optimizing the balance
      between the cardiovascular benefits and bleeding risks of antiplatelet therapy.
      Recent advances in the pharmacogenetics of thienopyridines open the realistic
      prospect of a personalized choice of the most appropriate antiplatelet agent and
      tailored dose adjustment for an individual patient.

PMID- 20059332
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune-mediated hypercoagulable
      disorder caused by antibodies to platelet factor 4 (PF4) and heparin. HIT
      develops in temporal association with heparin therapy and manifests either as an
      unexplained thrombocytopenia or thrombocytopenia complicated by thrombosis. The
      propensity for thrombosis distinguishes HIT from other common drug-induced
      thrombocytopenias. Diagnosing HIT in hospitalized patients is often challenging
      because of the frequency of heparin use, occurrence of thrombocytopenia from
      other causes, and development of asymptomatic PF4/heparin antibodies in patients
      treated with heparin. This review summarizes our current understanding of the
      pathogenesis, clinical features, diagnostic criteria, and management approaches
      in HIT.

PMID- 20059335
TI  - H5N1 Avian influenza: preventive and therapeutic strategies against a pandemic.
AB  - Avian influenza H5N1 viruses that have spread to a number of countries in Asia,
      the Middle East, and Africa have the potential to cause a pandemic. The most
      effective public health intervention strategy is to combine preventive
      vaccination with nonpharmaceutical intervention strategies and enhanced
      surveillance activities. H5N1 vaccines are poorly immunogenic even at high doses;
      an adjuvant is needed for enhancement of immunogenicity and for dose-sparing.
      Lack of effective, yet safe, adjuvants is the limiting factor for candidate
      vaccines that utilize egg-dependent or egg-independent manufacturing
      technologies. Hence, developing novel adjuvants is crucial for pandemic influenza
      vaccine development. Although the use of antiviral drugs is also an important
      public health countermeasure for preventing and treating influenza, the emergence
      of drug-resistant strains of avian H5N1 viruses underscores the need to develop
      not only new drugs but other novel preventive and therapeutic strategies such as
      vaccines.

PMID- 20059333
TI  - Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23.
AB  - In contrast to the regulation of calcium homeostasis, which has been extensively
      studied over the past several decades, relatively little is known about the
      regulation of phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part
      of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is
      modulated by PTH, 1,25(OH)(2)-vitamin D (1,25(OH)(2)D), dietary and serum
      phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively
      regulated by 1,25(OH)(2)D and serum phosphorus and negatively regulated, through
      yet unknown mechanisms, by the phosphate-regulating gene with homologies to
      endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1).
      In turn, FGF23 inhibits the synthesis of 1,25(OH)(2)D, and it may negatively
      regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands.
      However, FGF23 synergizes with PTH to increase renal phosphate excretion by
      reducing expression of the renal sodium-phosphate cotransporters NaPi-IIa and
      NaPi-IIc in the proximal tubules. Most insights gained into the regulation of
      phosphate homeostasis by these factors are derived from human genetic disorders
      and genetically engineered mice, which are reviewed in this paper.

PMID- 20059336
TI  - Controversies in the use of drug-eluting stents for acute myocardial infarction:
      a critical appraisal of the data.
AB  - Acute myocardial infarction is a common and life-threatening presentation of
      coronary artery disease in adults. In the settings of ST-segment elevation
      myocardial infarction and non-ST-segment elevation myocardial infarction,
      significant mortality benefit has been observed in randomized trials of coronary
      stent procedures compared with medical therapy alone. However, data regarding
      procedural choices, and particularly stent choices, are limited, and significant
      controversy exists. Drug-eluting stents were introduced in the United States in
      2003 and have been widely adopted based on profound reduction in restenosis. Yet
      recent years have witnessed a decline in use of drug-eluting stents in the
      setting of myocardial infarction due to long-term safety concerns. We review the
      current data regarding drug-eluting stent performance relative to bare metal
      stents in the setting of acute myocardial infarction with regard to
      effectiveness, safety, and the need for adjunctive long-term pharmacologic
      therapy.

PMID- 20059334
TI  - HIV-1 vaccine development after STEP.
AB  - Despite more than 25 years of concerted worldwide research, the development of a
      safe and effective HIV-1 vaccine remains elusive. Prototype antibody-based and T
      cell-based HIV-1 vaccines have failed to show efficacy in clinical trials to
      date. Next-generation HIV-1 vaccine candidates are in various stages of
      preclinical and clinical development, but key scientific obstacles pose major
      challenges for the field. Critical hurdles include the enormous global diversity
      of the virus and the challenges associated with generating broadly reactive
      neutralizing antibody and cellular immune responses. We review the current state
      of the HIV-1 vaccine field and outline strategies that are being explored to
      overcome these roadblocks.

PMID- 20059337
TI  - Arrhythmogenic cardiomyopathy: etiology, diagnosis, and treatment.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) has a prevalence of at
      least 1 in 1000, is a leading cause of sudden cardiac death in people aged < or
      =35 years, and accounts for up to 10% of deaths from undiagnosed cardiac disease
      in the <65 age group. The classic form of the disease has an early predilection
      for the right ventricle, but recognition of left-dominant and biventricular
      subtypes has prompted proposal of the broader term arrhythmogenic cardiomyopathy.
      The clinical profile of the disease bridges the gap between the cardiomyopathies
      and inherited arrhythmia syndromes. The early "concealed" phase is characterized
      by propensity toward ventricular tachyarrhythmia in the setting of well-preserved
      morphology, histology, and ventricular function. As the disease progresses,
      however, myocyte loss, inflammation, and fibroadiposis become evident. Up to 40%
      of cases harbor rare variants in genes encoding components of the desmosome,
      specialized intercellular junctions that confer mechanical strength to cardiac
      and epithelial tissue, and may also participate in signaling networks. Phenotypic
      heterogeneity and the nonspecific nature of associated features complicate
      clinical diagnosis, which requires multipronged cardiovascular investigation
      rather than a single test. Development of a prospectively validated risk
      stratification algorithm for the full disease spectrum remains the foremost
      clinical challenge.

PMID- 20059338
TI  - Contemporary use of ventricular assist devices.
AB  - The introduction of the heart lung machine more than 50 years ago proved in
      principle that heart function can be replaced, albeit for short periods. This was
      followed by attempts to produce total or partial artificial hearts that could
      function for prolonged periods of time. Progress in this field has been
      intermittent but has accelerated considerably in the past 10 years, with
      ventricular assist devices (VADs) reaching an impressive degree of sophistication
      and complexity owing to the contributions from clinicians, engineers, scientists,
      industrialists, and others. This review describes the currently available types
      of VADs, their current clinical use, the patient selection process, the trend
      toward use of VADs in patients with less severe heart failure, and the use of
      VADs for myocardial recovery in combination with novel pharmacological
      strategies, gene therapy, and cell therapy.

PMID- 20059339
TI  - Stem cells in the treatment of heart disease.
AB  - Progenitor cells residing in bone marrow, adipose tissue, and skeletal muscle or
      circulating in the blood are capable of improving myocardial function in
      preclinical models. In contrast, early clinical studies using bone marrow cells
      have shown mixed results and reflect our incomplete understanding of underlying
      mechanisms. Recent identification of various cardiac precursor cells has
      suggested an endogenous reservoir for cell-based repair. However, confronted with
      massive cardiac cell loss, inventive strategies and enabling technologies are
      required to mobilize or deliver functionally competent progenitor cells to sites
      of injury or to effectively stimulate endogenous repair. We review our present
      knowledge in this promising and rapidly evolving development in cardiovascular
      medicine and highlight obstacles as well as opportunities.

PMID- 20059340
TI  - Hepatocellular carcinoma: novel molecular approaches for diagnosis, prognosis,
      and therapy.
AB  - The genomic era is changing the understanding of cancer, although translation of
      the vast amount of data available into decision-making algorithms is far from
      reality. Molecular profiling of hepatocellular carcinoma (HCC), the most common
      cause of death among cirrhotic patients and a fast-growing malignancy in Western
      countries, is enabling the advancement of novel approaches to disease diagnosis
      and management. Most HCCs arise on a cirrhotic liver, and predictably, an
      accurate genomic characterization will allow the identification of
      procarcinogenic signals amenable to selective targeting by chemopreventive
      strategies. Molecular diagnosis is currently feasible for small tumors, but it
      has not yet been formalized by scientific guidelines. Molecular treatment is a
      reality: Sorafenib confers unprecedented survival benefits in patients at
      advanced stages. Genomic information from tumor and nontumoral tissue will aid
      prognosis prediction and facilitate the identification of oncogene addiction
      loops, providing the opportunity for more personalized medicine.

PMID- 20059342
TI  - Myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) represent a collection of stem cell disorders
      characterized by impaired hematopoiesis resulting in low peripheral blood counts.
      The majority of patients with MDS present with symptoms related to anemia;
      however, bleeding and infection are the most common causes of death. The median
      age of diagnosis is 72 and the median survival is 2.5 years. Lenalidomide,
      azacitidine, and decitabine are all FDA-approved agents to treat MDS; however,
      the only potential cure for MDS remains stem cell transplantation.

PMID- 20059341
TI  - Molecular diagnosis and therapy of kidney cancer.
AB  - Kidney cancer is not a single disease; it is made up of a number of cancers that
      occur in the kidney, each having a different histology, following a different
      clinical course, responding differently to therapy, and caused by a different
      gene. Study of the genes underlying kidney cancer has revealed that it is
      fundamentally a metabolic disorder. Understanding the genetic basis of cancer of
      the kidney has significant implications for diagnosis and management of this
      disease. VHL is the gene for clear cell kidney cancer. The VHL protein forms a
      complex that targets the hypoxia-inducible factors for ubiquitin-mediated
      degradation. Knowledge of this pathway provided the foundation for the
      development of novel therapeutic approaches now approved for treatment of this
      disease. MET is the gene for the hereditary form of type 1 papillary renal
      carcinoma and is mutated in a subset of sporadic type 1 papillary kidney cancers.
      Clinical trials are currently ongoing with agents targeting the tyrosine kinase
      domain of MET in sporadic and hereditary forms of papillary kidney cancer. BHD is
      the gene for the hereditary type of chromophobe kidney cancer. It is thought to
      be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling
      pathways. Hereditary leiomyomatosis renal cell carcinoma, a hereditary form of
      type 2 papillary renal carcinoma, is caused by inactivation of a Krebs cycle
      enzyme due to mutation. Knowledge of these kidney cancer gene pathways has
      enabled new approaches in the management of this disease and has provided the
      foundation for the development of targeted therapeutics.

PMID- 20059343
TI  - Nanotechnology applications in surgical oncology.
AB  - Surgery is currently the most effective and widely used procedure in treating
      human cancers, and the single most important predictor of patient survival is a
      complete surgical resection. Major opportunities exist to develop new and
      innovative technologies that could help the surgeon to delineate tumor margins,
      to identify residual tumor cells and micrometastases, and to determine if the
      tumor has been completely removed. Here we discuss recent advances in
      nanotechnology and optical instrumentation, and how these advances can be
      integrated for applications in surgical oncology. A fundamental rationale is that
      nanometer-sized particles such as quantum dots and colloidal gold have functional
      and structural properties that are not available from either discrete molecules
      or bulk materials. When conjugated with targeting ligands such as monoclonal
      antibodies, peptides, or small molecules, these nanoparticles can be used to
      target malignant tumor cells and tumor microenvironments with high specificity
      and affinity. In the "mesoscopic" size range of 10-100 nm, nanoparticles also
      have large surface areas for conjugating to multiple diagnostic and therapeutic
      agents, opening new possibilities in integrated cancer imaging and therapy.

PMID- 20059344
TI  - Emerging molecular targets for the treatment of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat
      accumulation in the absence of significant ethanol consumption, viral infection,
      or other specific causes of liver disease. Currently the most common chronic
      liver disease, affecting 30% of the Western world, NAFLD may progress to
      cirrhosis and end-stage liver disease and may increase the risk of developing
      diabetes and cardiovascular disease. Although its pathogenesis is unclear, NAFLD
      is tightly associated with insulin resistance and the metabolic syndrome. No
      established treatment exists, and current research is targeting new molecular
      mechanisms that underlie NAFLD and associated cardiometabolic disorders. This
      review discusses some of these emerging molecular mechanisms and their
      therapeutic implications for the treatment of NAFLD: microRNAs, incretin
      analogs/antagonists, liver-specific thyromimetics, AMP-activated protein kinase
      activators, and nuclear receptors farnesoid X receptor and pregane X receptor.

PMID- 20059345
TI  - Metabolic surgery to treat type 2 diabetes: clinical outcomes and mechanisms of
      action.
AB  - Several gastrointestinal (GI) operations that were designed to promote weight
      loss can powerfully ameliorate type 2 diabetes mellitus (T2DM). Although T2DM is
      traditionally viewed as a chronic, relentless disease in which delay of end-organ
      complications is the major treatment goal, GI surgery offers a novel endpoint:
      complete disease remission. Ample data confirm the excellent safety and efficacy
      of conventional bariatric operations-especially Roux-en-Y gastric bypass and
      laparoscopic adjustable gastric banding-to treat T2DM in severely obese patients.
      Use of experimental procedures as well as conventional bariatric operations is
      increasingly being explored in less obese diabetic patients, with generally
      favorable results, although further assessment of risk:benefit profiles is
      needed. Mounting evidence indicates that certain operations involving intestinal
      diversions improve glucose homeostasis through varied mechanisms beyond reduced
      food intake and body weight, for example by modulating gut hormones. Research to
      elucidate such mechanisms should facilitate the design of novel
      pharmacotherapeutics and dedicated antidiabetes GI manipulations. Here we review
      evidence regarding the use and study of GI surgery to treat T2DM, focusing on
      available published reports as well as results from the Diabetes Surgery Summit
      (DSS) in Rome and the World Congress on Interventional Therapies for T2DM in New
      York City.

PMID- 20059346
TI  - Genetic aspects of pancreatitis.
AB  - Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of
      the pancreas with unpredictable severity, complications, and clinical courses.
      Growing evidence for genetic risk and modifying factors, plus strong evidence
      that only a minority of patients with these disorders are heavy alcohol drinkers,
      has revolutionized our concept of these diseases. Once considered a self
      inflicted injury, pancreatitis is now recognized as a complex inflammatory
      condition like inflammatory bowel disease. Genetic linkage and candidate gene
      studies have identified six pancreas-targeting factors that are associated with
      changes in susceptibility to acute and/or chronic pancreatitis, including
      cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease
      inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator
      (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients
      with mutations in these genes are at increased risk of pancreatitis caused by a
      variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies
      are reporting new polymorphisms, as well as complex gene x gene and gene x
      environmental interactions.

PMID- 20059347
TI  - Structural variation in the human genome and its role in disease.
AB  - During the last quarter of the twentieth century, our knowledge about human
      genetic variation was limited mainly to the heterochromatin polymorphisms, large
      enough to be visible in the light microscope, and the single nucleotide
      polymorphisms (SNPs) identified by traditional PCR-based DNA sequencing. In the
      past five years, the rapid development and expanded use of microarray
      technologies, including oligonucleotide array comparative genomic hybridization
      and SNP genotyping arrays, as well as next-generation sequencing with "paired
      end" methods, has enabled a whole-genome analysis with essentially unlimited
      resolution. The discovery of submicroscopic copy-number variations (CNVs) present
      in our genomes has changed dramatically our perspective on DNA structural
      variation and disease. It is now thought that CNVs encompass more total
      nucleotides and arise more frequently than SNPs. CNVs, to a larger extent than
      SNPs, have been shown to be responsible for human evolution, genetic diversity
      between individuals, and a rapidly increasing number of traits or susceptibility
      to traits; such conditions have been referred to as genomic disorders. In
      addition to well-known sporadic chromosomal microdeletion syndromes and Mendelian
      diseases, many common complex traits including autism and schizophrenia can
      result from CNVs. Both recombination- and replication-based mechanisms for CNV
      formation have been described.

PMID- 20059348
TI  - Surgical innovations arising from the Iraq and Afghanistan wars.
AB  - The delivery of combat casualty care poses numerous challenges including austere
      conditions, limited supplies and medical personnel, and multiple simultaneous
      patients. However, the exigent circumstances of the battlefield compel the
      development of research and the advancement of adaptive, practical medical
      technologies to support and sustain military health. In Operation Enduring
      Freedom (OEF) and Operation Iraqi Freedom (OIF), modern changes in medical
      management, coupled with improved protective gear and evacuation capabilities,
      have facilitated the highest survival rate in combat history.

PMID- 20059349
TI  - Medicare part D: ongoing challenges for doctors and patients.
AB  - The Medicare Modernization Act was intended to improve access to prescription
      drugs for millions of seniors, by providing a range of benefit packages with
      different prices and different formularies for beneficiaries to choose from. The
      major challenge for physicians has been to recognize when a Medicare beneficiary
      has coverage versus when that patient is in the "doughnut hole" where Medicare
      beneficiaries do not have coverage and therefore have to pay the full cost of the
      drugs out-of-pocket. A second challenge is that different Medicare beneficiaries
      are enrolled in different drug plans, and drugs that are covered in some plans
      are not covered in other plans.

PMID- 20059350
TI  - Bovine serum albumin glutaraldehyde for completely sutureless laparoscopic
      heminephrectomy in a survival porcine model.
AB  - INTRODUCTION: Laparoscopic partial nephrectomy (LPN) has not received widespread
      clinical application because of its technical challenge. Bovine serum albumin
      glutaraldehyde (BSAG) is a hemostatic agent that is independent of the clotting
      cascade. We evaluated the use of BSAG as the sole agent for parenchymal and
      collecting system closure during LPN in a survival porcine model. METHODS:
      Eighteen pigs underwent hilar clamping and LPN by longitudinal excision of the
      lateral one-third of the right kidney. The opened collecting system was covered
      with oxidized cellulose to prevent BSAG seepage into the urinary tract. BSAG was
      allowed to set for 10 or 5 minutes. Twelve animals underwent survival LPN BSAG
      only closure; six control pigs were acutely studied using saline. Urinary
      extravasation was evaluated by injection of furosemide and indigo carmine, and
      then evaluating the renal surface and bladder catheter drainage for dye. A
      subjective bleeding score was assigned after hilum unclamping. At 6 weeks, BSAG
      kidneys were harvested for burst pressure testing and histopathological analysis.
      RESULTS: All 12 pigs survived for 6 weeks. No pigs had urinary extravasation.
      Mean percentage of kidney removed by weight was 19%. Mean warm ischemia time was
      29 minutes. Five pigs required a second BSAG application to achieve a bleeding
      score of 0. Mean arterial and collecting system burst pressures were 301.8 and
      322.4 mm Hg, respectively. Mean postoperative creatinine increase was 0.07 mg/dL.
      CONCLUSION: BSAG for completely sutureless LPN in a survival porcine model was
      feasible.

PMID- 20059351
TI  - Preliminary experience with laparoscopic ureteropelvic junction release in the
      treatment of ureteropelvic junction obstruction.
AB  - OBJECTIVE: To review our experience with laparoscopic ureteropelvic junction
      (UPJ) release in the treatment of UPJ obstruction (UPJO) in adults. PATIENTS AND
      METHODS: We retrospectively reviewed 44 consecutive patients who underwent
      laparoscopic treatment of UPJO at our institution between December 2000 and April
      2008. Patient characteristics, perioperative data, intraoperative findings
      leading to a decision to perform UPJ release, and outcomes were recorded. Mean
      patient age was 47.4 years (range 20-60 years). RESULTS: UPJ release was
      performed as definitive treatment in 9 of 47 laparoscopic procedures for UPJO.
      The obstruction was right-sided in five and left-sided in four patients. Three
      (33%) patients were previously treated with either balloon dilation or
      endopyelotomy, or both. Intraoperative findings included (1) significant
      scarring, inflammation, or fibrosis, (2) adherent bands between a crossing vessel
      and the UPJ, or (3) obvious constricting periureteral bands. A crossing vessel
      was observed in seven patients (78%). Mean operative time, estimated blood loss,
      and length of stay were 370.1 +/- 76.9 minutes, 24.4 +/- 31.3 mL, and 1.4 +/- 0.5
      days, respectively. At a mean follow-up of 25.1 +/- 17.3 months, a 78% overall
      success rate was achieved. UPJ release was most successful in the patients in the
      "significant scarring, inflammation, or fibrosis" category (100%). CONCLUSION:
      Although pyeloplasty remains the preferred treatment for UPJO, UPJ release can be
      successful in certain circumstances, particularly when significant scarring,
      inflammation, or fibrosis appears to be the primary etiology of the obstruction.
      Further investigation is warranted to help define the specific clinical
      situations in which UPJ release may be beneficial.

PMID- 20059352
TI  - Cold renal ischemia: comparison of efficacy between two techniques of cooling, in
      a swine model.
AB  - OBJECTIVES: In a swine model of renal ischemia, we compared the effectiveness of
      the transurethral retrograde cold saline perfusion technique to the traditional
      method of renal cooling with ice slush, in achieving adequate parenchymal
      temperatures for functional preservation of the organ. Physiological and
      histological effects were also assessed. METHODS: Twenty-four domestic male pigs
      were sampled into four groups to be submitted to a 60-minute ischemia of the left
      kidney without cooling, with either one of the two cooling techniques (cold
      saline retrograde perfusion or ice slush), or sham surgery. All of them had also
      a concomitant right nephrectomy. Renal cortical and medullary temperatures were
      recorded throughout the experiment. Urinary output was measured, and serum renal
      function tests were carried on, pre- and postoperatively. After 5 days, the
      animals were euthanized and their kidneys were submitted to histological
      analysis. RESULTS: Mean renal temperature fell in both groups submitted to kidney
      cooling. With ice slush, a faster drop was observed and a lower minimum
      temperature was achieved (5.0 degrees C in the cortex and 6.3 degrees C in the
      medulla, vs. 25.4 degrees C and 24.9 degrees C with retrograde cooling). In the
      other groups, temperature was unchanged. Urinary output and serum creatinine
      worsened after the experiment, but without significant differences among groups.
      The histological analysis showed no differences among the four groups, for the
      studied ischemia time. CONCLUSIONS: Ice slush and retrograde perfusion of cold
      saline are both effective for cooling the kidney during ischemia. Ice slush is
      faster in doing so, and it allows much lower temperatures to be achieved in the
      renal parenchyma. With ischemia time of 60 minutes, no significant differences on
      the occurrence of functional and histological alterations were detected, even for
      the group without a cooling procedure.

PMID- 20059353
TI  - Esophageal actinomycosis in a fifty-three-year-old man with HIV: case report and
      review of the literature.
AB  - Patients with advanced HIV infection commonly present with esophageal
      symptomatology most frequently due to Candida, cytomegalovirus, or herpes simplex
      virus. We present a case of a 53-year-old man with AIDS and prior esophageal
      candidiasis and oral aphthous ulcerations, who developed actinomycosis of the
      esophagus. This article aims to review clinical characteristics of this and seven
      previously reported cases occurring in HIV-infected patients. Esophageal
      actinomycosis is frequently preceded by other esophageal disease that likely
      results in breach of the mucosal barrier, allowing establishment of the
      infection. Health care providers should be aware of this rare entity,
      particularly in those with recurring symptoms, so that a timely diagnosis can be
      made.

PMID- 20059354
TI  - Prevalence and interactions of patient-related risks for nonadherence to
      antiretroviral therapy among perinatally infected youth in the United States.
AB  - Adherence to antiretroviral regimens continues to be a significant problem in HIV
      infected individuals facing a lifetime of therapy. Youth who were infected
      through perinatal transmission enter into adolescence often with a history of
      multiple medication regimens. Thus, adherence can be a particularly important
      issue in these young people, as medication options can often be limited. This was
      a cross-sectional, observational study to determine the prevalence of personal
      barriers to adherence and to identify associations among the following barriers
      in subjects 12 to 24 years old: mental health barriers, self-efficacy and outcome
      expectancy, and structural barriers. Among the 368 study participants, 274
      (74.5%) were adherent and 94 (25.5%) were nonadherent to highly active
      antiretroviral therapy (HAART). No significant differences were found between
      adherent and nonadherent subjects according to mental health disorders. Adherence
      was associated with some but not all structural barriers. Both self-efficacy and
      outcome expectancy were significantly higher in adherent versus nonadherent
      subjects (p < 0.0001). In subjects with low self-efficacy and outcome expectancy,
      adherence differed according to the presence or absence of either mental health
      or structural barriers, similar to findings in behaviorally- infected
      adolescents. Interventions that address the breadth and clustering of adherence
      barriers in adolescents are needed to have the maximum chance for positive
      effects.

PMID- 20059355
TI  - Pediatric HIV clinical care resources and management practices in Asia: a
      regional survey of the TREAT Asia pediatric network.
AB  - Characterizing intraregional differences in current pediatric HIV care and
      treatment in Asia can guide the development of clinical practice guidelines and
      improve the understanding of local resource availability. The Therapeutics
      Research, Education, and AIDS Training in Asia (TREAT Asia) Pediatric Program is
      a collaboration of clinics and referral hospitals studying pediatric HIV outcomes
      in the region. A Web-based survey to characterize clinical management practices
      and monitoring resources was developed and distributed to 20 sites in January
      2008. Seventeen (85%) sites from 6 countries responded through April 2008; 14
      (82%) were hospital-based and 16 (94%) were public facilities. Of 4050 HIV
      infected children under care, 3606 (89%) were on antiretroviral treatment; 80%
      were on their first mono-, dual-, or triple-drug regimen and 74% were on
      nevirapine- or efavirenz-based regimens. Fifteen (88%) sites had consistent
      access to polymerase chain reaction (PCR) testing for infant diagnosis. All sites
      had access to CD4 testing, with 13 (76%) routinely monitoring patients every 3-6
      months; 7 (41%) sites monitored viral load at 6- to 12-month intervals. Although
      there is some variation in clinical practices, high levels of treatment and
      monitoring resources were available at these sites. The availability of PCR for
      early infant diagnosis positions them to implement recent WHO recommendations to
      treat HIV-infected children younger than 1 year of age. This information will be
      used to develop future research and programs to support children with HIV in
      Asia.

PMID- 20059356
TI  - Initial outcomes of provider-initiated routine HIV testing and counseling during
      outpatient care at a rural Ugandan hospital: risky sexual behavior, partner HIV
      testing, disclosure, and HIV care seeking.
AB  - Provider-initiated routine HIV testing is being scaled up throughout the world,
      however, little is known about the outcomes of routine HIV testing on subsequent
      behavior. This study examined the initial outcomes of provider-initiated routine
      HIV testing at a rural Ugandan hospital regarding partner HIV testing, sexual
      risk behavior, disclosure, and HIV care seeking. In a prospective cohort study,
      245 outpatients receiving routine HIV testing completed baseline and 3-month
      follow-up interviews. After receiving routine HIV testing the percentage of
      participants engaging in risky sex decreased from 70.1% to 50.3% among HIV
      negative and from 75.0% to 53.5% among HIV-positive participants, the percentage
      knowing their partner(s)' HIV status increased from 18.7% to 34.3% of HIV
      negative and from 14.3% to 35.7% of HIV-positive participants. Among those
      reporting risky sex at baseline, HIV-positive participants were more likely to
      eliminate risky sex in general and specifically to become abstinent at follow-up
      than were HIV-negative participants. Similarly, unmarried participants who were
      risky at baseline were more likely to become safe in general, become abstinent,
      and start 100% condom use than were married/cohabitating participants. Rates of
      disclosure were high. Over 85% of those who tested HIV positive enrolled in care.
      Routine HIV testing in this setting may promote earlier HIV diagnosis and access
      to care but leads to only modest reductions in risky sexual behavior. To fully
      realize the potential HIV prevention benefits of routine HIV testing an emphasis
      on tailored risk-reduction counseling may be necessary.

PMID- 20059357
TI  - A novel tetravalent dengue vaccine is well tolerated and immunogenic against all
      4 serotypes in flavivirus-naive adults.
AB  - BACKGROUND. Sanofi Pasteur has developed a tetravalent dengue vaccine (TDV)
      against the world's most common arbovirus infection. METHODS. We assessed the
      safety and immunogenicity of the TDV in healthy adults randomized into 2 groups.
      Group 1 received 3 TDV injections at months 0, 4, and 12-15; group 2 received
      saline placebo at month 0 and then 2 TDV injections at months 4 and 12-15.
      Adverse events were recorded, and biological parameters and viremia levels were
      measured. Neutralizing antibodies against 4 World Health Organization (WHO)
      reference strains were measured before and after vaccinations. RESULTS. A total
      of 33 participants were enrolled in each group. Demographic characteristics were
      comparable. No vaccine-related serious adverse event was reported. The most
      common systemic reactions were headache, malaise, and myalgia. Low viremia levels
      were detected, mainly of serotype 4. Immune response increased with successive
      vaccine doses. All participants seroconverted against all 4 serotypes after
      receiving 3 doses at 0, 4, and 12-15-months, and almost all seroconverted after 2
      doses given 8-11 months apart. CONCLUSIONS. Sanofi Pasteur's TDV was well
      tolerated and induced full seroconversion against all WHO reference strain
      serotypes after 3 doses.

PMID- 20059358
TI  - Oral human papillomavirus (HPV) infection--are there implications for HPV
      vaccination?

PMID- 20059360
TI  - Insulin clamp-derived measurements of insulin sensitivity and insulin secretion
      in lean and obese asian type 2 diabetic patients.
AB  - BACKGROUND: The aim of this study was to investigate insulin sensitivity and
      secretion in lean and obese Asian (Thai) type 2 diabetic patients. METHODS:
      Insulin sensitivity and insulin secretion was assessed with the hyperinsulinemic
      euglycemic (80 mU/m(2) per min) and hyperglycemic clamp technique in 9 lean and
      10 obese patients with type 2 diabetes and 4 lean and 4 obese nondiabetic control
      subjects. RESULTS: Obese type 2 diabetics had a lower M-value (sensitivity to
      exogenous insulin) than lean type 2 diabetics (8.7 +/- 1.3 versus 16.5 +/- 1.6 mg
      . fat free mass kg(-1) . min(-1), P < 0.001) and obese control subjects (15.9 +/-
      4.0 mg . fat free mass kg(-1) . min(-1), P < 0.05). Insulin sensitivity (M-value)
      was similar in lean type 2 diabetics as compared to lean nondiabetic control
      subjects. During the hyperglycemic clamp, the first (P < 0.001) and second phase
      (P < 0.02) of insulin and C-peptide response (P < 0.02) was significantly
      decreased in lean type 2 diabetics as compared to lean nondiabetic subjects. In
      obese type 2 diabetics, the first and second phase of insulin response was
      significantly decreased (P < 0.05) compared to obese nondiabetic subjects.
      CONCLUSIONS: Obese type 2 diabetics have significant defects in both insulin
      sensitivity and insulin secretion whereas lean type 2 diabetics demonstrate
      primarily a defect in insulin secretion. Lean diabetics have similar insulin
      sensitivity when compared to healthy age- and sex-matched nondiabetic subjects
      during the euglycemic clamp study, suggesting the lack of significant insulin
      resistance in lean type 2 diabetics.

PMID- 20059361
TI  - The effect of colesevelam hydrochloride on insulin sensitivity and secretion in
      patients with type 2 diabetes: a pilot study.
AB  - BACKGROUND: This study evaluated the effect of colesevelam hydrochloride on
      insulin sensitivity, potential binding to glucose, and chronic effect(s) on
      fasting and postprandial glucose and insulin in patients with type 2 diabetes
      mellitus. METHODS: Patients meeting inclusion criteria were withdrawn from all
      antidiabetes agents for 2 weeks and randomized to colesevelam 3.75 grams/day (n =
      17) or placebo (n = 18) for 8 weeks. Hyperinsulinemic-euglycemic clamp studies
      were performed at baseline (week -1) and weeks 2 and 8. A meal tolerance test was
      conducted at weeks -1, 0, 2, and 8. The meal tolerance test and study drug were
      coadministered at week 0 to assess the direct effect of colesevelam on glucose
      absorption. RESULTS: Insulin sensitivity as measured by the insulin clamp method
      did not change, but the Matsuda Index, a measure of whole-body insulin
      sensitivity calculated from postmeal tolerance test glucose and insulin levels,
      increased significantly within the colesevelam group from baseline to week 8 with
      last observation carried forward (P = 0.020). The postprandial area under the
      curve for glucose decreased with colesevelam versus placebo at weeks 2 and 8 with
      last observation carried forward (P = 0.012 and P = 0.061, respectively); the
      area under the curve for insulin did not decrease in concert with the decrease in
      area under the curve for glucose at week 2 (P = 0.585). Colesevelam had no effect
      on postmeal tolerance test glucose levels at week 0. CONCLUSIONS: These results
      suggest that colesevelam has no effect on peripheral insulin sensitivity or
      glucose absorption, but may improve glucose control by improving whole-body
      insulin sensitivity, although not by an acute effect on glucose absorption.
      CLINICAL TRIAL IDENTIFIER: NCT00361153.

PMID- 20059362
TI  - A Simple and robust automated kinase profiling platform using luminescent ADP
      accumulation technology.
AB  - Kinases continue to be one of the most important targets in today's drug
      discovery efforts. Following the identification of lead compounds through
      screening efforts, it is important to profile these leads against other kinases
      within that family, as well as from other families, to ascertain potential off
      target effects. Because many kinase assays require the use of different
      substrates, optimization time and costs during profiling can be prohibitive. Here
      we demonstrate the versatility of a luminescent ADP accumulation assay, where one
      set of reagents can be used for a wide variety of kinases with differing K(m app)
      for ATP and substrates. Assay sensitivity allows for the use of low enzyme
      concentrations and small percent ATP conversion levels while still maintaining
      high signal:background ratios. We have used a simple, inexpensive automated
      pipetting system to automate the entire process from enzyme optimization through
      generation of compound IC(50) values. Agreement with literature values proves
      this combination of chemistry and instrumentation provides a simple, yet robust
      solution for automated kinase profiling.

PMID- 20059364
TI  - The contribution of selection and genetic constraints to phenotypic divergence.
AB  - Although divergent natural selection is common in nature, the extent to which
      genetic constraints bias evolutionary trajectories in its presence remains
      largely unknown. Here we develop a general framework to integrate estimates of
      divergent selection and genetic constraints to estimate their contributions to
      phenotypic divergence among natural populations. We apply these methods to
      estimates of phenotypic selection and genetic covariance from sexually selected
      traits that have undergone adaptive divergence among nine natural populations of
      the fly Drosophila serrata. Despite ongoing sexual selection within populations,
      differences in its direction among them, and genetic variance for all traits in
      all populations, divergent sexual selection only weakly resembled the observed
      pattern of divergence. Accounting for the influence of genetic covariance among
      the traits significantly improved the alignment between observed and predicted
      divergence. Our results suggest that the direction in which sexual selection
      generates divergence may depend on the pattern of genetic constraint in
      individual populations, ultimately restricting how sexually selected traits may
      diversify. More generally, we show how evolution is likely to proceed in the
      direction of major axes of genetic variance, rather than the direction of
      selection itself, when genetic variance-covariance matrices are ill conditioned
      and genetic variance is low in the direction of selection.

PMID- 20059365
TI  - Biological cluster evaluation for gene function prediction.
AB  - Recent advances in high-throughput omics techniques render it possible to decode
      the function of genes by using the "guilt-by-association" principle on
      biologically meaningful clusters of gene expression data. However, the existing
      frameworks for biological evaluation of gene clusters are hindered by two
      bottleneck issues: (1) the choice for the number of clusters, and (2) the
      external measures which do not take in consideration the structure of the
      analyzed data and the ontology of the existing biological knowledge. Here, we
      address the identified bottlenecks by developing a novel framework that allows
      not only for biological evaluation of gene expression clusters based on existing
      structured knowledge, but also for prediction of putative gene functions. The
      proposed framework facilitates propagation of statistical significance at each of
      the following steps: (1) estimating the number of clusters, (2) evaluating the
      clusters in terms of novel external structural measures, (3) selecting an optimal
      clustering algorithm, and (4) predicting gene functions. The framework also
      includes a method for evaluation of gene clusters based on the structure of the
      employed ontology. Moreover, our method for obtaining a probabilistic range for
      the number of clusters is demonstrated valid on synthetic data and available gene
      expression profiles from Saccharomyces cerevisiae. Finally, we propose a network
      based approach for gene function prediction which relies on the clustering of
      optimal score and the employed ontology. Our approach effectively predicts gene
      function on the Saccharomyces cerevisiae data set and is also employed to obtain
      putative gene functions for an Arabidopsis thaliana data set.

PMID- 20059366
TI  - Synchrony and stability of food webs in metacommunities.
AB  - Synchrony has fundamental but conflicting implications for the persistence and
      stability of food webs at local and regional scales. In a constant environment,
      compensatory dynamics between species can maintain food web stability, but
      factors that synchronize population fluctuations within and between communities
      are expected to be destabilizing. We studied the dynamics of a food web in a
      metacommunity to determine how environmental variability and dispersal affect
      stability by altering compensatory dynamics and average species abundance. When
      dispersal rate is high, weak correlated environmental fluctuations promote food
      web stability by reducing the amplitude of compensatory dynamics. However, when
      dispersal rate is low, weak environmental fluctuations reduce food web stability
      by inducing intraspecific synchrony across communities. Irrespective of dispersal
      rate, strong environmental fluctuations disrupt compensatory dynamics and
      decrease stability by inducing intermittent correlated fluctuations between
      consumers in local food webs, which reduce both total consumer abundance and
      predator abundance. Strong correlated environmental fluctuations lead to (i)
      spatially asynchronous and highly correlated local consumer dynamics when
      dispersal is low and (ii) spatially synchronous but intermediate local consumer
      correlation when dispersal is high. By controlling intraspecific synchrony,
      dispersal mediates the capacity of strong environmental fluctuations to disrupt
      compensatory dynamics at both local and metacommunity scales.

PMID- 20059367
TI  - Isotretinoin-induced encephalopathy.
AB  - A 16-year-old male started on isotretinoin 80 mg daily for acne developed
      persistent headache 3 weeks later, with myoclonus and confusion 10 weeks later.
      During initial hospital assessment his Glasgow Coma Scale score fell acutely to 8
      and he required ventilation. Brain imaging and cerebrospinal fluid (CSF) analysis
      were normal and an electroencephalogram (EEG) showed features of encephalopathy.
      No cause was found. He was extubated after 24 hours and made a full recovery.
      This is the first report of a generalized encephalopathy thought likely to be due
      to isotretinoin.

PMID- 20059368
TI  - Treatment of osteoarthritis in hypertensive patients.
AB  - IMPORTANCE OF THE FIELD: Osteoarthritis and hypertension commonly co-exist.
      Treatment of osteoarthritis in hypertensive patients is a therapeutic challenge
      due to the adverse effects of some analgesics, especially non-steroidal anti
      inflammatory drugs (NSAIDs), on blood pressure. Even small drug-induced rises in
      blood pressure due to therapy may significantly increase cardiovascular risk in
      these patients if sustained over the long term. Patients treated with certain
      classes of antihypertensive agent may be at particular risk of deterioration in
      blood pressure control with NSAID therapy. NSAIDs may also increase
      cardiovascular risk due to mechanisms other than by raising blood pressure. AREAS
      COVERED IN THIS REVIEW: We discuss the management of osteoarthritis in the
      hypertensive patient, review the evidence for the effects of paracetamol and
      NSAIDs on blood pressure and discuss novel therapeutic strategies for
      osteoarthritis that might diminish this problem. A literature search was
      undertaken in PubMed including the years 1980 - 2009. WHAT THE READER WILL GAIN:
      Insight will be gained into the complexity of treating patients with co-existent
      osteoarthritis and hypertension and into possible new approaches to treating
      osteoarthritis symptoms effectively in these patients while minimising any
      adverse impact on blood pressure control. TAKE HOME MESSAGE: There are ways to
      minimise the adverse impact of treatment of osteoarthritis on blood pressure
      control in hypertensive patients.

PMID- 20059370
TI  - Major salivary gland sonography in Sjogren's syndrome: diagnostic value of a
      novel ultrasonography score (0-12) for parenchymal inhomogeneity.
AB  - OBJECTIVE: To validate ultrasonographic criteria for examination of the major
      salivary glands in the diagnosis of primary Sjogren's syndrome (SS). METHOD: A
      total of 209 consecutive patients with rheumatic diseases were selected according
      to the American-European Consensus Group (AECG) classification criteria for SS.
      One hundred and fifteen patients had primary SS, 44 had secondary SS, and 50 had
      sicca symptoms, and 36 subjects served as asymptomatic controls. This cohort was
      analysed for size, echogenicity, parenchymal inhomogeneity, focal changes, and
      posterior borders of the major salivary glands by ultrasonography (US). A novel
      US score for parenchymal inhomogeneity (0-12) was assigned and its diagnostic
      accuracy evaluated. RESULTS: Ultrasonographic abnormalities of salivary glands
      were detected in 107/115 (93.0%) patients with primary SS, in 12/44 (27.3%) with
      secondary SS, in 25/50 (50.0%) with sicca symptoms, and in 4/36 (11.1%)
      asymptomatic controls. Area under the receiver operating characteristic curve
      (AUC-ROC) for US inhomogeneity score was highly significant [0.96 +/- 0.01; 95%
      confidence interval (CI) 0.94-0.99, p < 0.000] for primary SS, with a sensitivity
      to specificity ratio of 91/83 for parotid and 93/90 for submandibular glands.
      Setting the cut-off US inhomogeneity score at 6 resulted in the best ratio of
      specificity (90.0%) to sensitivity (95.1%), with a positive predictive value of
      72% and a negative predictive value of 96%. A US inhomogeneity score >or= 6 was
      closely correlated with positive biopsy (p < 0.000) and scintigraphy findings (p
      < 0.000). CONCLUSIONS: We demonstrate the high diagnostic value of a novel US
      score for parenchymal inhomogeneity (0-12) that could serve as a useful single US
      criterion in the evaluation of salivary gland involvement in primary SS.

PMID- 20059369
TI  - Work ability: a new outcome measure in rheumatoid arthritis?
AB  - OBJECTIVES: To assess the relationship between disease activity and work ability,
      quality of life (QoL), and fatigue in patients with RA during a 12-month course
      of the tumour necrosis factor (TNF)-blocking agent adalimumab. METHODS: RA
      patients in the working age category who started treatment with adalimumab were
      included consecutively and followed up for 12 months. Generalized estimating
      equation (GEE) analyses were used to study relationships between disease activity
      and the outcome variables work ability, QoL, and fatigue at baseline, 6 months,
      and 12 months. Disease activity was measured using the 28-joint Disease Activity
      Score (DAS28), quality of life was assessed with the Rheumatoid Arthritis
      specific Quality of Life instrument (RAQoL), and fatigue was assessed using the
      Checklist Individual Strength (CIS) questionnaire and the Need for Recovery scale
      (NFR). RESULTS: After 1 year, markedly improvement was seen not only in the DAS28
      (from 5.2 +/- 1.2 to 3.1 +/- 1.6) but also in work ability, RAQoL, and work
      related fatigue, which improved by 50, 29, and 34%, respectively. At all three
      time points strong significant associations were observed between DAS28 and work
      ability, RAQoL, and work-related fatigue and this relationship remained strong
      after adjustment for confounders. CONCLUSIONS: Disease activity was associated
      with QoL, work-related fatigue, and work ability in a group of RA patients
      treated with adalimumab for 1 year. As improvement in these factors influences
      work participation positively and work ability measures more than health status,
      the current results suggest that simple tools such as work ability should be used
      more frequently as outcome measures in trials with RA patients.

PMID- 20059371
TI  - Immigration check for neutrophils in RA lining: laminin alpha5 low expression
      regions act as exit points.
AB  - OBJECTIVE: A correlation exists between the absence of alpha5-laminin and transit
      checkpoint fenestrations in vascular basement membranes. We hypothesized that
      similar laminin alpha5 low expression regions might exist in synovial lining,
      which, although lacking basement membrane, contains all basement membrane
      components in its interstitial matrix. METHODS: Laminin alpha4 and alpha5 chains
      and lactoferrin were stained using immunofluorescence and cathepsin G and
      neutrophil elastase using immunoperoxidase. Quantitative real-time polymerase
      chain reaction (qRT-PCR) was used to measure laminin alpha4 and alpha5 mRNA copy
      numbers in cultured synovial fibroblasts, without/with tumour necrosis factor
      alpha (TNFalpha) and interleukin-1beta (IL-1beta). RESULTS: Laminin alpha4 and
      alpha5 chains were found in the intercellular matrix in synovial lining samples
      of trauma and revision total hip replacements. Laminin alpha5 was weaker in
      osteoarthritis (OA) and rheumatoid arthritis (RA), and RA synovial lining also
      contained local low expression areas. Double staining disclosed convergence of
      lactoferrin-degranulating neutrophils towards these laminin alpha5 low expression
      regions. In cultured OA synovial fibroblasts, laminin alpha5 mRNA decreased (p <
      0.05) at 1 ng/mL TNFalpha and was not found at all in cultured resting or
      cytokine-stimulated RA fibroblasts. Degranulation of cathepsin G and neutrophil
      elastase was seen in neutrophils passing through blood vessels or synovial
      lining. CONCLUSIONS: Migrating neutrophils in RA seem to use laminin alpha5 chain
      low expression regions to exit synovial tissue to enter synovial fluid.
      Transmigrating neutrophils remodel the intercellular matrix by releasing their
      proteolytic granular contents to enhance these low expression checkpoints and/or
      to produce chemotactic stimuli. In RA fibroblasts this is facilitated by cytokine
      mediated down-regulation or lack of laminin alpha5 synthesis.

PMID- 20059372
TI  - Acceptability of switching adalimumab from a prefilled syringe to an
      autoinjection pen.
AB  - OBJECTIVE: To assess patients' acceptance of switching adalimumab from a
      prefilled syringe to an autoinjection pen. METHODS: A two-phase cross-sectional
      study. The first phase consisted of a 2-h information/education session to
      present the pen and assist patients in learning its use. At the end of the
      session, patients completed a self-administered questionnaire regarding
      usefulness of the meeting. At the next hospital pharmacy dispensing visit the
      autoinjection pen was provided. Four single-use prefilled devices (40 mg/0.8 ml
      every other week) were provided. RESULTS: The study population included 55
      patients (rheumatoid arthritis 29, psoriatic arthritis 17, ankylosing spondylitis
      9). Attendees showed a high degree of satisfaction with the education session
      (between 72.7 and 90.9% rated the relevant items of the questionnaire in the
      highest category). Fifty-one patients participated in the second phase of the
      study. Patients reported 100% adherence to treatment with the autoinjection pen.
      The percentage of patients self-administering medication increased from 51 to 84%
      and the percentage attending primary care for injection decreased from 33 to 2%.
      Pain at the injection site was significantly reduced with the use of the
      autoinjection pen. The mean (sd) visual analogue scale (VAS) score was 3.52
      (2.26) for the syringe compared with 2.02 (2.16) for the pen (p < 0.001). Forty
      four (86.3%) patients considered that the use of the autoinjection pen was easier
      than the syringe, and 96.1% chose the pen as their preferred delivery system.
      CONCLUSIONS: This study provides further evidence to support the use of the
      autoinjection pen as a delivery option for adalimumab therapy.

PMID- 20059374
TI  - Safety issues of iron chelation therapy in patients with normal range iron stores
      including thalassaemia, neurodegenerative, renal and infectious diseases.
AB  - An increased number of thalassaemia patients treated with effective chelation
      therapy protocols are achieving body iron levels similar to those of normal
      individuals. Iron chelation therapy has also been recently used in a number of
      other categories of patients with no excess body iron load such as
      neurodegenerative, renal and infectious diseases. Chelation therapy in the
      absence of iron overload in the latter conditions raises many safety issues
      including chelator overdose toxicity and toxicity related to iron and other
      essential metal deficiencies. Preliminary preclinical and clinical toxicity
      evidence suggest that deferoxamine and deferasirox can only be safely used for
      these non-iron loaded conditions for short-term treatments of a few weeks,
      whereas deferiprone can be used for longer term treatments of many months. The
      selection of the chelating drug and appropriate dose protocols for targeting
      specific organs and conditions is critical for the safety of patients with normal
      iron stores. Chelation therapy is likely to play a major role as adjuvant,
      alternative or main therapy in many non-iron loading conditions in the
      forthcoming years.

PMID- 20059375
TI  - Role of the Fcgamma receptor IIIA-V/F158 polymorphism in susceptibility to
      systemic lupus erythematosus and lupus nephritis: a meta-analysis.
AB  - OBJECTIVE: To perform a meta-analysis to assess the risk of the Fc-gamma receptor
      type IIIA (FcgammaRIIIA)-V/F158 polymorphism for lupus nephritis and systemic
      lupus erythematosus (SLE). METHODS: We surveyed studies on V/F158 and SLE and/or
      lupus nephritis using Medline, Blackwell, and EMBASE databases up to January
      2009. Sufficient original data were available to calculate odds ratios (ORs) for
      SLE and/or lupus nephritis based on the American College of Rheumatology (ACR)
      criteria. Two investigators independently assessed the data quality and extracted
      the data. RESULTS: The F158 allele presented overall consistent association
      evidence for SLE, SLE without nephritis, and lupus nephritis [OR 1.27, 95%
      confidence interval (CI) 1.13-1.43; OR 1.20, 95% CI 1.05-1.37; OR 1.15, 95% CI
      1.04-1.28, respectively]. FF homozygosity had a dose-response relationship for
      SLE with maximal OR 1.68 (95% CI 1.26-2.23). It also strongly influenced the risk
      of lupus nephritis and of SLE without nephritis, with maximal OR 1.30 (95% CI
      1.04-1.64) and 1.43 (95% CI 1.07-1.92), respectively. Ethnic subgroup analyses
      revealed that the F158 allele was significantly higher in SLE patients of
      European and Asian descent [OR 1.30 (95% CI 1.07-1.58) and OR 1.24 (95% CI 1.04
      1.48), respectively] but not in SLE patients of African descent and was only
      highly associated with lupus nephritis in those of Asian descent [OR 1.26 (95% CI
      1.06-1.50)]. The FF genotype was significantly associated with SLE in those of
      European and Asian descent, with maximal OR 1.61 (95% CI 1.03-2.53) and 1.70 (95%
      CI 1.12-2.58), respectively, but not for lupus nephritis and SLE without
      nephritis of any subgroup. CONCLUSIONS: The FcgammaRIIIA-V/F158 polymorphism
      might be a common susceptibility factor for SLE and lupus nephritis and play an
      important role in the overall development of SLE, showing different risks within
      ethnic populations, which should provide novel insights into the pathogenesis of
      the disease.

PMID- 20059376
TI  - Evaluation of an antibody-free ADP detection assay: ADP-Glo.
AB  - Identification of kinase, especially protein kinase, modulators through high
      throughput screening (HTS) has become a common strategy for drug discovery
      programs in both academia and the pharmaceutical industry. There are a number of
      platform technologies that can be used for measuring kinase activities. However,
      there is none that fits all criteria in terms of sensitivity, ATP tolerance,
      robustness, throughput, and cost-effectiveness. Therefore, development of a
      homogeneous and robust HTS assay for some kinase targets is still challenging. We
      recently evaluated the ADP-Glo assay from Promega. This is a homogeneous, signal
      increase assay that measures ADP production from a kinase reaction by coupled
      enzymes that first convert ADP to ATP and subsequently quantifies ATP using
      luciferase in the presence of luciferin. Since the unused ATP in the reaction is
      depleted prior to ADP to ATP conversion, this assay shows excellent sensitivity
      over a wide range of ATP concentrations. We demonstrate that ADP-Glo assay can be
      used for 2 kinase targets that belong to different classes, and compare the
      results of compound profiling with SPA and FP assay technologies.

PMID- 20059377
TI  - Comparison of bioluminescent kinase assays using substrate depletion and product
      formation.
AB  - Assays for ATPases have been enabled for high-throughput screening (HTS) by
      employing firefly luciferase to detect the remaining ATP in the assay. However,
      for any enzyme assay, measurement of product formation is a more sensitive assay
      design. Recently, technologies that allow detection of the ADP product from
      ATPase reactions have been described using fluorescent methods of detection. We
      describe here the characterization of a bioluminescent assay that employs firefly
      luciferase in a coupled-enzyme assay format to enable detection of ADP levels
      from ATPase assays (ADP-Glo, Promega Corp.). We determined the performance of the
      ADP-Glo assay in 1,536-well microtiter plates using the protein kinase Clk4 and a
      1,352 member kinase focused combinatorial library. The ADP-Glo assay was compared
      to the Clk4 assay performed using a bioluminescence ATP-depletion format (Kinase
      Glo, Promega Corp). We performed this analysis using quantitative HTS (qHTS)
      where we determined potency values for all library members and identified
      approximately 300 compounds with potencies ranging from as low as 50 nM to >10
      microM, yielding a robust dataset for the comparison. Both assay formats showed
      high performance (Z'-factors approximately 0.9) and showed a similar potency
      distribution for the actives. We conclude that the bioluminescence ADP detection
      assay system is a viable generic alternative to the widely used ATP-depletion
      assay for ATPases and discuss the advantages and disadvantages of both
      approaches.

PMID- 20059378
TI  - Easy, rapid, and cost-effective methods for identifying carriers of recurrent
      GJB2 mutations causing nonsyndromic hearing impairment in the Greek population.
AB  - A variety of techniques have been developed for screening the GJB2 gene for known
      and unknown mutations, especially the most common mutation in the Caucasian
      population, the c.35delG. Other mutations that have been so far characterized in
      the GJB2 gene seem to have different geographical distributions, and therefore
      there is an interest in identifying recurrent mutations specific for each
      population and developing easy and rapid screening techniques. Here we present
      easy screening protocols for already identified recurrent mutations in the Greek
      population. Developing easy, rapid, and cost-effective screening methods will
      facilitate the detection of GJB2 recurrent mutation carriers, at large, in the
      Greek population.

PMID- 20059379
TI  - Novel GNE mutations in hereditary inclusion body myopathy patients of non-Middle
      Eastern descent.
AB  - Autosomal recessive hereditary inclusion body myopathy (HIBM or IBM2) is a
      progressive adult onset muscle wasting disorder characterized by sparing of the
      quadriceps. IBM2 is also known as distal myopathy with rimmed vacuoles or nonaka
      myopathy. IBM2 is associated with mutations in the UDP-GlcNAc 2-Epimerase/ManNAc
      Kinase gene (GNE). GNE is the rate-limiting enzyme of N-Acetylneuraminate
      (Neu5Ac, Sialic acid) biosynthesis. The GNE coding region of 64 symptomatic
      patients were sequenced. Twenty-eight patients were found to bear GNE mutations.
      Ten novel mutations were identified among nine patients, including four nonsense
      (p.R8X, p.W204X, p.Q436X, and p.S615X) and five missense (p.R71W, p.I142T,
      p.I298T, p.L556S, and p.E2G) variations spanning both the epimerase and kinase
      domains of GNE. Additionally, a synonymous variation (p.Y591Y, codon tac > tat)
      was seen in a patient bearing compound heterozygous nonsynonymous mutations
      (p.S615X and p.Y675H). Six of the nine are Caucasian, one patient is Taiwanese,
      one patient is Asian Indian, and one patient is of European descent. These
      findings further expand the clinical and genetic spectrum of IBM2.

PMID- 20059380
TI  - A c.1363C>T (p.R455X) nonsense mutation of RB1 gene in a southern Chinese
      retinoblastoma pedigree.
AB  - Retinoblastoma (RB) is the most common malignant intraocular tumor in children.
      Fifty percent of RB patients are carriers of a predisposing germline mutation
      with high penetrance. RB1 has been identified as the only pathological gene. We
      present the rapid detection of an RB1 gene mutation in a Han pedigree of two RB
      patients from southern China. Total RNA was extracted from whole blood for
      reverse transcriptase-polymerase chain reaction (PCR) to analyze RB1 transcripts,
      and genomic DNA for PCR and direct sequencing to test RB1 exons. Allele-specific
      PCR was used to verify the mutation. The results showed that the bilaterally
      affected son and the unilaterally affected father were both heterozygous for the
      nonsense mutation c.1363C>T (p.R455X) in exon 14 of RB1. Our studies suggest the
      molecular basis of RB in this Chinese family and provide further evidence that
      codon 455 is one of the recurrent spots for mutations in RB1.

PMID- 20059381
TI  - Detection of large rearrangements in the cystic fibrosis transmembrane
      conductance regulator gene by multiplex ligation-dependent probe amplification
      assay when sequencing fails to detect two disease-causing mutations.
AB  - AIMS: Most of the over 1600 mutations and sequence variants identified to date in
      the cystic fibrosis transmembrane conductance regulator (CFTR) gene are point
      mutations or small deletions/insertions detectable by conventional sequencing.
      However, large rearrangements (deletions, duplications, or insertion/deletion
      mutations) have recently been reported to constitute 1-2% of CFTR mutations. The
      CFTR sequencing protocol at ARUP Laboratories interrogates the coding regions of
      all 27 exons and all intron/exon boundaries of the gene. This study was
      undertaken to determine whether testing for large gene rearrangements could
      improve the mutation detection rate. RESULTS: Nine cases with abnormal
      quantitative pilocarpine iontophoresis sweat chloride (SC) values (>60 mEq/L) and
      20 cases with borderline SC levels (40-60 mEq/L) with only one or no mutations
      detected by the ARUP 32 mutation panel, including the 23 mutations recommended by
      American College of Medical Genetics (ACMG) for carrier screening, followed by
      sequencing, were tested using a multiplex ligation-dependent probe amplification
      (MLPA) assay. MLPA analysis identified one deletion among nine patients with SC
      >60 who had previously been tested with sequencing. None of the cases with
      borderline SC levels showed rearrangements. CONCLUSION: The MLPA assay for
      detection of large rearrangements may be valuable in individuals with positive SC
      levels where one or no mutations have been identified by sequencing.

PMID- 20059382
TI  - Angiotensin-converting enzyme insertion/deletion gene polymorphism in a Tunisian
      healthy and acute myocardial infarction population.
AB  - INTRODUCTION: The role of the insertion/deletion (I/D) polymorphism in the
      angiotensin-converting enzyme gene (ACE) on acute myocardial infarction (AMI) is
      controversial. OBJECTIVES: To assess the effect of the ACE I/D polymorphism on
      AMI compared with the healthy controls and its relationship with serum ACE
      activity in a Tunisian population. DESIGN AND METHODS: A total of 119 patients
      with AMI were compared with 238 healthy controls from the same geographical area.
      ACE genotyping was determined by polymerase chain reaction, and serum ACE
      activity was measured with N-[3-(2-furylacryloyl]-L-phenylalanyl-L-glycyl-L
      glycine as substrate. RESULTS: The ACE I/D polymorphism was significantly
      different between patients and controls (p < 0.0001). The frequencies of the DD
      genotype and the D allele were statistically higher in patients with AMI as
      compared with the controls and were associated with increased risk of AMI (DD vs.
      ID and II: odds ratio = 4.27, p < 0.0001, 95% confidence interval = 2.65-6.86; D
      vs. I: odds ratio = 3.15, p < 0.0001, 95% confidence interval = 2.26-4.40). This
      association was independent of other cardiovascular risk factors but dyslipidemia
      (p = 0.002) that was not represented in AMI patients with II genotype and in a
      lower extent with hypertension (p < 0.05). Serum ACE activity was significantly
      higher in AMI patients with ACE DD genotype compared with the subjects with ID or
      II genotype (p = 0.034) and was not correlated with other cardiovascular risk
      factors. CONCLUSIONS: ACE DD genotype associated with higher serum ACE activity
      is increased in the studied population and might be clinically useful as markers
      to assess risk for AMI.

PMID- 20059383
TI  - The management of renal caliceal calculi with a newly designed ureteroscope: a
      rigid ureteroscope with a deflectable tip.
AB  - PURPOSE: To evaluate the indications for, and the effects of, the management of
      renal caliceal calculi with deflectable tip rigid ureteroscopy. PATIENTS AND
      METHODS: We designed a new deflectable tip rigid ureteroscope, and 175 patients
      with renal caliceal calculi received deflectable tip rigid ureteroscopic
      lithotripsy with a holmium laser. RESULTS: From December 2003 to December 2007,
      the procedure was successfully performed in all patients with a mean operative
      time of 28 minutes (range 19-45 min). The mean size of renal caliceal stones was
      1.3 cm (range 0.8-2.4 cm). Seventeen patients had concurrent proximal ureteral
      calculi. The mean lithotripsy time was 11 minutes (range 5-22 min), and the mean
      discharge time was 3 days after operation. The overall stone-free rate at the 1
      month follow-up was 83%. CONCLUSION: Ureteroscopic lithotripsy with the novel
      deflectable tip rigid ureteroscope is a safe procedure and combines the
      advantages of rigid and flexible ureteroscopy, especially for renal caliceal
      calculi of relatively small size.

PMID- 20059384
TI  - Contrast-enhanced ultrasonography evaluation of radiofrequency ablation of the
      prostate: a canine model.
AB  - BACKGROUND AND PURPOSE: Currently, there is no reliable method of monitoring the
      propagation of radiofrequency lesions in real time. We report our animal
      experience using contrast-enhanced ultrasonography (CEUS) to evaluate the lesion
      produced by radiofrequency ablation (RFA) in a canine model and investigate the
      feasibility to predict these lesions. MATERIALS AND METHODS: Five male beagle
      dogs underwent RFA of the prostate. Radiofrequency was delivered under
      transrectal ultrasonography guidance. We created a lesion in the right and left
      lateral lobes of canine prostate. Post-RFA lesion size was measured with
      conventional ultrasonography and contrast-enhanced low-mechanical index perfusion
      imaging (ESAOTE DU8, CnTI) with a second-generation contrast agent (Sonovue). The
      prostates were assessed for a contrast void corresponding to the ablated tissue.
      All dogs were then immediately killed, and the prostates were harvested for
      pathologic analysis. The gross RFA lesions were measured to compare lesion size
      with that measured using CEUS. RESULTS: The RFA lesions could not be imaged
      accurately in real time with conventional grayscale or power Doppler sonography.
      With CEUS imaging, a clear lesion was identified at the site of each RFA
      application. As measured by CEUS, the lesions volume averaged 1.30 +/- 0.50
      cm(3), compared with 1.32 +/- 0.53 cm(3) by measurement in the gross specimen (p
      = 0.324). CONCLUSIONS: CEUS appears to be an accurate modality for immediate
      monitoring of RFA procedure. Further study is necessary to assess the clinical
      utility of CEUS for monitoring RFA of localized prostate cancer.

PMID- 20059385
TI  - The role of haptic feedback in laparoscopic training using the LapMentor II.
AB  - INTRODUCTION: Laparoscopic surgery has become the standard of care for many
      surgical diseases. Haptic (tactile) feedback (HFB) is considered an important
      component of laparoscopic surgery. Virtual reality simulation (VRS) is an
      alternative method to teach surgical skills to surgeons in training. Newer VRS
      trainers such as the Simbionix Lap Mentor II provide significantly improved
      tactile feedback. However, VRSs are expensive and adding HFB software adds an
      estimated cost of $30,000 to the commercial price. The HFB provided by the Lap
      Mentor II has not been validated by an independent party. We used the Simbionix
      Lap Mentor II in this study to demonstrate the effect of adding an HFB mechanism
      in the VRS trainer. MATERIALS AND METHODS: The study was approved by the
      University of Cincinnati Institutional Review Board. Twenty laparoscopically
      novice medical students were enrolled. Each student was asked to perform three
      different tasks on the Lap Mentor II and repeat each one five times. The chosen
      tasks demanded significant amount of traction and counter traction. The first
      task was to pull leaking tubes enough and clip them. The second task was
      stretching a jelly plate enough to see its attachments to the floor and cut these
      attachments. In the third task, the trainee had to separate the gallbladder from
      its bed on the liver. The students were randomized into two groups to perform the
      tasks with and without HFB. We used accuracy, speed, and economy of movement as
      scales to compare the performance between the two groups. The participants also
      completed a simple questionnaire that highlighted age, sex, and experiences in
      videogame usage. RESULTS: The two groups were comparable in age, sex, and
      videogame playing. No differences in the accuracy, the economy, and the speed of
      hand movement were noticed. In fact, adding HFB to the Lap Mentor II simulator
      did not contribute to any improvement in the performance of the trainees.
      Interestingly, we found that videogame expert players tend to have faster and
      more economic motion in their dominant hands. However, the performance accuracy
      was not significantly affected. CONCLUSION: The presence of HFB has less effect
      than it thought to be on the performance of the novice trainees. This may suggest
      that better HFB is still needed. However, there may be visual compensation for
      the lack of haptics. Playing videogames has a positive impact on economy, and the
      speed of the dominant had motion without affecting its accuracy. Further research
      is needed to clarify the value of haptics to the expert surgeon and compare it to
      the new trainees.

PMID- 20059389
TI  - Laparoscopic management of impalpable testis in children, new classification,
      lessons learned, and rare anomalies.
AB  - INTRODUCTION: Cryptorchidism is the most common genitourinary anomaly in male
      children. About 20% of cryptorchid testicles are impalpable. Laparoscopy has
      become one of the important diagnostic modalities for the management of
      impalpable testes. The aim of the present study was in highlighting the lessons
      and rare anomalies encountered during the management of impalpable testes in
      children over a period of 10 years in a single pediatric surgery center and to
      establish a new classification that better describes the anomalies. MATERIALS AND
      METHODS: A retrospective review of 93 laparoscopic explorations for nonpalpable
      testes between 1998 and 2008 was conducted. Demographic data, intraoperative
      findings and management, associated anomalies, and postoperative follow-up were
      collected and analyzed. A new laparoscopic classification is described. RESULTS:
      Age range was 7 months to 8 years. Twenty bilateral versus 73 unilateral
      impalpable testes were operated on. Four groups were established with subgroups
      in each group. Group 1 (vanishing syndrome) had 44 cases, group 2 (peeping
      testes) had 21 cases, group 3 (intra-abdominal testes) had 38 cases, and group 4
      (disorders of sex development) had 10 cases. Associated anomalies included 4
      cases of Down syndrome, 7 cases of neurologic impairment, 3 of renal anomalies, 3
      of cardiac anomalies, and 1 case of eye anomalies. Follow-up range was 1-6 years.
      CONCLUSIONS: A new laparoscopic classification is presented that better describes
      the anomalies and help-in planning the treatment of impalpable testes. Impalpable
      testes with Down syndrome are sometimes associated with bizarre anatomy. Parents
      should be well informed of all the possible findings, especially in bilateral
      cases.

PMID- 20059390
TI  - Thoracoscopic repair of congenital diaphragmatic hernia in infancy.
AB  - BACKGROUND: Minimally invasive surgical techniques, specifically the
      thoracoscopic approach, have been applied to congenital diaphragmatic hernia
      (CDH) with varying outcomes from selected centers. The aim of our study was to
      examine the rate of successful completion and compare outcomes between open and
      thoracoscopic approaches in CDH repair. METHODS: We performed a retrospective
      analysis of infants with CDH repair (From February 2004 to January 2008).
      Patients were divided into thoracoscopic and open groups, based on operative
      approach. We analyzed demographic, clinical, and hospitalization characteristics
      to compare the completion rate and outcomes in these two groups. RESULTS:
      Analysis of 31 infants with CDH (14 thorascocopic and 17 open) demonstrated no
      differences in sex (P = 0.132), age (P = 0.807), birthweight (P = 0.256), weight
      at operation (P = 0.647), pulmonary hypertension (P = 0.067), preoperative
      intensive care unit (ICU) days (P = 0.673), ventilator days (P = 0.944), or use
      of a patch (P = 0.999) between the groups. Seventy-nine percent of thoracoscopic
      operative approaches were completed successfully. There was a significant
      difference between the open and thoracoscopic groups with respect to estimated
      gestational age (39 versus 36.5 weeks; P = 0.006) and operating room time (70
      versus 145 minutes; P = 0.004). The total (P = 0.662), ICU (P = 0.889), and
      postoperative (P = 0.619) length of stay and days on ventilator (P = 0.705), as
      well as days until initial enteral feeds (P = 0.092), were not significantly
      different between groups. There were no deaths and no evidence of recurrence,
      with a mean follow-up of 346 days. CONCLUSIONS: In our early experience, the
      thoracoscopic approach for congenital diaphragmatic hernia repair was completed
      in 80% of our patient population with minimal exclusion criteria. Further study,
      with larger sample sizes, is needed to ascertain differences in outcomes, such as
      length of stay and initiation of enteral feeding.

PMID- 20059391
TI  - Laparoscopic excision of infarcted accessory spleen.
AB  - An accessory spleen is present in about 10-30% of the population and, usually,
      does not cause symptoms. We present a case report of an unusual presentation of
      accessory spleen infarction, with a literature review. A 12-year old male
      presented with acute left-upper quadrant pain that slowly resolved. An ultrasound
      and computed tomography scan showed a 3.5 x 2.5 x 2 cm solid mass abutting and
      displacing the splenic flexure of the colon, with surrounding inflammatory
      changes. This was interpreted as a colonic duplication cyst, and the boy was
      treated with antibiotics and underwent elective laparoscopic exploration. It was
      removed laparoscopically without complication and, on pathologic examination,
      proved to be consistent with an infarcted accessory spleen. Less than two dozen
      similar cases of accessory spleen infarction have been reported in the
      literature, most presenting with acute abdominal pain. Preoperative diagnoses
      included appendicitis, ovarian torsion, neoplasm, and, in our case, colonic
      duplication. The natural course of infarcted accessory spleen would be to
      atrophy, but, even with advanced imaging techniques, it may be impossible to
      diagnose infarcted accessory spleen with enough confidence to avoid surgery.

PMID- 20059392
TI  - Mutation Analysis and Prenatal Exclusion of Fibrodysplasia Ossificans Progressiva
      in a Chinese Fetus.
AB  - Aims: Fibrodysplasia ossificans progressiva (FOP) is a rare and severely
      disabling autosomal dominant disorder characterized by congenital malformations
      of the great toes and progressive postnatal heterotopic ossification. A point
      mutation in the activin receptor IA (ACVR1) gene is the cause of FOP. Most of the
      reported cases of FOP are sporadic and caused by de novo mutations; however, some
      rare cases can also result from parental germline mosaicism associated with a
      greater risk of recurrence in successive pregnancies. Therefore, once the
      pathogenic mutation has been identified in the proband, it is relative cheaper
      and important to perform prenatal diagnostic tests to exclude the recurrence risk
      of FOP in subsequent pregnancies. In this study, we first investigated the
      mutation in the ACVR1 gene in a Chinese FOP patient and then performed prenatal
      tests to exclude the risk of recurrence in the patient's unborn sibling. Methods:
      A couple visited our clinic with their 4-year-old son, who was clinically
      diagnosed with FOP, for genetic counseling. Genetic testing was performed by
      amplifying all the nine exons of the ACVR1 gene using the conventional polymerase
      chain reaction. Further, DNA sequencing was used to determine the mutation based
      on the results of a mutation screening using denaturing high-performance liquid
      chromatography. Subsequently, a prenatal test was performed using the same
      technique as that used for the proband. Results: A recurrent single nucleotide
      mutation c.617 G>A (R206H) of the ACVR1 gene was identified in the patient;
      however, both the parents had a normal ACVR1 gene. Prenatal tests showed that the
      fetus did not carry the pathogenic mutation. Conclusion: The results confirmed
      that a recurrent single nucleotide mutation c.617 G>A (R206H) was the genetic
      cause of FOP and explored the utility of prenatal testing in excluding the risk
      of recurrence in the successive pregnancy.

PMID- 20059394
TI  - Ureteral complications in the era of laparoscopic living donor nephrectomy: do we
      need to preserve the gonadal vein with the specimen?
AB  - BACKGROUND AND PURPOSE: The aim of this study was to analyze the ureteral
      complication rate in recipients transplanted with laparoscopically retrieved
      kidneys in our institution's 8-year experience when the gonal vein was not
      preserved with the specimen during the donor procedure. PATIENTS AND METHODS: We
      reviewed the records of 800 consecutive laparoscopic donor nephrectomy patients.
      Donor sex, age, body mass index, warm ischemia time, hospital length of stay,
      donor and recipient serum creatinine levels, and incidence and type of
      complications including the incidence of ureteral complications were recorded.
      RESULTS: Mean patient age was 39 +/- 10 years. Mean body mass index was 27 +/- 5.
      A total of 482 cases were treated purely laparoscopically. Of them, 318 were
      performed hand assisted. Seven hundred and ninety-three procedures were done on
      the left side and seven were done on the right side. The overall rate of
      intraoperative complications was 2.9%. The overall open conversion rate was 1.4%.
      The overall rate of postoperative complications was 3.9%. The postoperative day-7
      serum creatinine values of the donors were 1.4 +/- 0.3 mg/dL. Mean creatinine in
      all patients at 1 week after transplantation was 1.5 +/- 0.2 mg/dL. We had one
      case of ureteral stricture in the recipients of laparoscopically procured kidneys
      without gonadal vein preservation technique among 800 patients. CONCLUSION:
      Gonadal vein preservation with the entire specimen during laparoscopic donor
      nephrectomy procedure is not a necessary step to protect periureteral blood
      supply to prevent ureteral strictures.

PMID- 20059396
TI  - Four new HIV-1 group N isolates from Cameroon: Prevalence continues to be low.
AB  - Analysis of 3555 HIV-seropositive specimens, collected in Cameroon from 2002 to
      2006, led to the identification of four HIV-1 group N infections based on
      differential seroreactivity to HIV env-derived peptides and proteins and
      confirmation by nucleic acid amplification. Group N prevalence continues to be
      low accounting for only 0.1% of HIV infections in Cameroon. Near full-length
      genomic sequences were obtained from viral RNA or proviral DNA by PCR
      amplification of overlapping fragments for three isolates, 06CM-U14296, 06CM
      U14842, and 02CM-SJGddd. Two genome segments, partial pol and env-nef, were
      obtained from viral RNA for the fourth isolate, 02CM-TIM0217. With the four group
      N isolates identified in this study and group N sequences previously reported,
      eight near full-length and five partial genome sequences are now available.
      Despite genetic divergence from HIV-1 group M and O, all of the group N
      infections evaluated by five commercial HIV immunoassays were detected.

PMID- 20059395
TI  - Identification of a potential pharmacological sanctuary for HIV type 1 in a
      fraction of CD4(+) primary cells.
AB  - We have identified a subset of HIV-susceptible CD4(+)CCR5(+) cells in human PBMCs
      that can efficiently exclude protease inhibitors (PI) due to high P-glycoprotein
      (P-gp) efflux activity. Phenotypically these cells are heterogeneous, include
      both T and non-T cells, and some display markers of memory cells. Cells with high
      P-gp represent 16-56% (median = 37.3) of all CD4(+)CCR5(+) cells in healthy
      donors, and are selectively depleted in HIV-1-infected individuals (4.1-33%,
      median = 10.1). A fraction of primary cells productively infected by HIV-1, in
      vitro, have high P-gp pump activity, demonstrating that infection does not
      inhibit P-gp function. In agreement with these data, HIV-susceptible cells
      expressing high levels of P-gp require higher levels of PI for complete
      inhibition of virus spread. We conclude that the PI concentrations achieved in
      plasma could be suboptimal for full inhibition of virus spread in high P-gp
      cells, indicating that they may represent a pharmacological sanctuary for HIV-1.

PMID- 20059397
TI  - T cell responses of HIV-infected children after administration of inactivated or
      live attenuated influenza vaccines.
AB  - Live-attenuated influenza vaccine (LAIV) prevents significantly more cases of
      influenza in immune-competent children than the trivalent inactivated vaccine
      (TIV). We compared the T cell responses to LAIV or TIV in HIV-infected children.
      IFN-gamma-ELISPOT for the three vaccine-contained influenza strains, two
      mismatched strains, and phytohemagglutinin (PHA), was performed at 0, 4, and 24
      weeks postimmunization in 175 HIV-infected children randomly assigned to LAIV or
      TIV. The contribution of CD8 T cells to the influenza-specific response (CD8
      ELISPOT) was evaluated by CD8-cell depletion. CD8 T cells accounted for > or =87%
      of the total influenza-ELISPOT. At baseline, total influenza-ELISPOT and CD8
      ELISPOT values were similar or higher in TIV compared with LAIV recipients. Four
      and 24 weeks after TIV, total influenza-ELISPOT and CD8-ELISPOT results were
      significantly lower than baseline results (p < or = 0.001). Responses to PHA also
      tended to decrease at 4 weeks after TIV (p = 0.06), but rebounded to baseline
      levels at 24 weeks. Four weeks after LAIV, total influenza-ELISPOT responses to
      vaccine-contained strains A H3N2 and B significantly decreased. Other ELISPOT
      values at 4 weeks and all values at 24 weeks were similar to the baseline values.
      At 4 and 24 weeks, TIV compared to LAIV administration resulted in a
      significantly greater decrease in influenza-specific ELISPOT values for vaccine
      contained influenza A strains (p < or = 0.02). Responses to PHA also tended to
      decrease more in TIV recipients (p = 0.07). HIV-infected children immunized with
      TIV had significant and persistent decreases in ELISPOT responses to influenza.
      LAIV administration suppressed ELISPOT responses less. The clinical significance
      of these findings deserves further study.

PMID- 20059398
TI  - Neutralizing antibody titers conferring protection to macaques from a
      simian/human immunodeficiency virus challenge using the TZM-bl assay.
AB  - We previously reported that passive transfer of polyclonal neutralizing
      antibodies (NAbs) sufficient to generate a titer of 1:38 in the plasma would
      confer sterilizing protection to 99% of macaques challenged intravenously with 75
      TCID(50) of SHIV(DH12). Neutralizing activity in that study was measured in an
      MT4 cell assay in which infection was completely blocked (EC(100)). In the
      current study, the TZM-bl system was used to measure EC(50) neutralizing titers
      in several of the same macaque plasma samples and the relationship between these
      titers and in vivo protection was determined. The antiviral EC(50) NAb titers
      measured in individual plasma samples were higher than those previously obtained
      in the MT4 system. Furthermore, the geometric mean EC(50) NAb titers against
      pseudotyped SHIV(DH12) were 33-fold greater than the EC(100) titers measured in
      the MT4 cell assay against the replication-competent SHIV(DH12) inoculated into
      animals. An augmented probit regression model was used to generate curves
      relating TZM-bl EC(50) NAb titers and protection from a virus challenge;
      estimated titers conferring various levels of protection were then determined. In
      TZM-bl assays using pseudotyped SHIV(DH12), representative percent in vivo
      protection/estimated EC(50) titers were 99%/1:4467, 90%/1:1175, 80%/1:676,
      50%/1:234, and 33%/1:141. Because it is likely that contributions from other arms
      of the immune system will contribute to vaccine-induced control, the range of
      EC(50) NAb titers we have derived may be more informative for evaluating the
      protective value of NAb activity from TZM-bl assays.

PMID- 20059399
TI  - Redox biocatalysis and metabolism: molecular mechanisms and metabolic network
      analysis.
AB  - Whole-cell biocatalysis utilizes native or recombinant enzymes produced by
      cellular metabolism to perform synthetically interesting reactions. Besides
      hydrolases, oxidoreductases represent the most applied enzyme class in industry.
      Oxidoreductases are attributed a high future potential, especially for
      applications in the chemical and pharmaceutical industries, as they enable highly
      interesting chemistry (e.g., the selective oxyfunctionalization of unactivated C
      H bonds). Redox reactions are characterized by electron transfer steps that often
      depend on redox cofactors as additional substrates. Their regeneration typically
      is accomplished via the metabolism of whole-cell catalysts. Traditionally,
      studies towards productive redox biocatalysis focused on the biocatalytic enzyme,
      its activity, selectivity, and specificity, and several successful examples of
      such processes are running commercially. However, redox cofactor regeneration by
      host metabolism was hardly considered for the optimization of biocatalytic rate,
      yield, and/or titer. This article reviews molecular mechanisms of oxidoreductases
      with synthetic potential and the host redox metabolism that fuels biocatalytic
      reactions with redox equivalents. The tools discussed in this review for
      investigating redox metabolism provide the basis for studies aiming at a deeper
      understanding of the interplay between synthetically active enzymes and metabolic
      networks. The ultimate goal of rational whole-cell biocatalyst engineering and
      use for fine chemical production is discussed.

PMID- 20059400
TI  - Glutaredoxin participates in the reduction of peroxides by the mitochondrial 1
      CYS peroxiredoxin in Saccharomyces cerevisiae.
AB  - The mechanism for regeneration of the active-site "peroxidatic" cysteine in 1-Cys
      peroxiredoxins is a matter of debate. Saccharomyces cerevisiae Prx1 is a
      mitochondrial enzyme belonging to the 1-Cys Prx, whereas Grx2 is involved in
      antioxidant defense and localizes at the mitochondria, so we hypothesized that it
      could be a perfect candidate to resolve the sulfenate in Prx1 with GSH. In vitro
      experiments with purified Prx1p and Grx2p demonstrate that Grx2p, at
      concentrations <1 microM, coupled to GSH, is a very efficient thiolic
      intermediary for the reduction of the peroxidatic Cys in Prx1p. Prx1p forms
      oligomeric aggregates natively, but depolymerizes down to a dimeric state after
      treatment with GSH. The catalytic cycle involves glutathionylation of dimeric
      Prx1p and deglutathionylation by Grx2p. Dihydrolipoamide, a genuine mitochondrial
      dithiol, can efficiently substitute for GSH. The activity is highest at alkaline
      pH, consistent with the conditions of active respiring mitochondria, and the
      process is highly specific for 1-Cys Prx because Grx2p is totally inactive with
      human PRX1, a typical 2-Cys Prx, as opposed to the promiscuity of Trx. Our
      results suggest that although Trx is the reductant involved in the reduction of
      peroxides by 2-Cys-Prx, Grx might be the natural resolving partner of 1-Cys Prx
      through a monothiolic mechanism.

PMID- 20059401
TI  - Women live longer than men: understanding molecular mechanisms offers
      opportunities to intervene by using estrogenic compounds.
AB  - Women live longer than men. Moreover, females live longer than males in some, but
      not all, experimental animals. The differences in longevity between genders are
      related to free radical production. Indeed, females produce less radicals only in
      animal species in which they live longer than males. This is because estrogens
      upregulate antioxidant longevity-related genes. These considerations have led us
      to postulate an extended concept of antioxidant in biology: an antioxidant is any
      nutritional, physiological, or pharmacological manipulation that increases the
      expression and activity of antioxidant genes or proteins. Phytoestrogens or other
      selective estrogen receptor modulators lower age-related diseases and prolong
      life span, at least in experimental animals. This provides rational bases to
      study their action in humans further.

PMID- 20059402
TI  - p27KIP1 expression in gastric cancer: differential pathways in the histological
      subtypes associated with Helicobacter pylori infection.
AB  - OBJECTIVE: Decreases in p27(KIP1) and C-MYC expression have been associated with
      Helicobacter pylori infection. Furthermore, C-MYC seems to be a transcriptional
      repressor of p27(KIP1). Therefore, in a series of gastric adenocarcinomas we
      studied the association of p27(KIP1) expression with H. pylori genotype (vacA,
      cagA, cagE and virB11) and the involvement of C-MYC in this process. MATERIAL AND
      METHODS: Expression of p27(KIP1) and C-MYC was determined by immunohistochemistry
      in 84 gastric adenocarcinoma samples and H. pylori infection and genotype were
      determined by polymerase chain reaction. RESULTS: Most p27(KIP1)-negative cases
      (94.0%) were H. pylori-positive and 44.8% were C-MYC-positive. In the diffuse
      gastric cancer subtype, p27-negative-C-MYC-positive was the most frequent
      combination (cluster II), and was associated with the more pathogenic H. pylori
      strains. Although an association with p27(KIP1) and H. pylori strain was found in
      the intestinal gastric cancer subtype, negativity for p27(KIP1) and C-MYC markers
      was the most frequent cluster, followed by cluster II, and both were present,
      independent of the H. pylori genotype. CONCLUSIONS: Reduced expression of
      p27(KIP1) was closely linked to H. pylori infection, and was dependent on the
      more pathogenic strains. Moreover, intestinal and diffuse subtypes showed
      distinct carcinogenic pathways influenced by H. pylori strains. These data add
      insight to the differential influence and relevance of H. pylori genotype in
      gastric cancer development.

PMID- 20059403
TI  - Impact of double-balloon enteroscopy findings on the management of Crohn's
      disease.
AB  - OBJECTIVE: It is estimated that 10%-30% of Crohn's disease (CD) patients have
      small-bowel lesions, but the exact frequency and clinical relevance of these
      findings are unknown. Double-balloon enteroscopy (DBE) enables endoscopic
      visualization of the small bowel. The aim of this study was to evaluate the use
      of DBE for detecting small-bowel lesions in CD patients suspected of having small
      bowel involvement. Furthermore, the clinical impact of adjusting treatment in
      these patients was assessed. MATERIAL AND METHODS: A prospective study was
      performed in a tertiary referral center. CD patients suspected of small-bowel
      involvement and in whom distal activity had previously been excluded were
      included. All patients underwent DBE, followed by step-up therapy in patients
      with small-bowel lesions. The presence of small-bowel lesions during DBE was
      noted and clinical outcome was assessed after adjusting therapy. RESULTS: Thirty
      five patients (70%) showed small-bowel lesions; these lesions could not be
      assessed by conventional endoscopy in 23 (46%). At 1-year follow-up, step-up
      therapy in 26 patients (74%) led to clinical remission in 23 (88%). This was
      confirmed by a significant decrease in Crohn's disease activity index and mucosal
      repair on second DBE. CONCLUSIONS: DBE showed a high frequency of small-bowel
      lesions in known CD patients with clinically suspected small-bowel activity. Most
      of these lesions were not accessible for conventional endoscopy. Adjusting
      treatment in patients with small-bowel CD involvement led to clinical remission
      and mucosal repair in the majority of cases.

PMID- 20059404
TI  - Dynamic changes in liver stiffness during the course of acute hepatitis A.
AB  - OBJECTIVE: Several recent studies have suggested that hepatic necroinflammation
      can alter the results of liver stiffness measurements (LSMs) obtained using the
      FibroScan device. However, the precise relationship between acute hepatic
      inflammation and LSMs remains unclear. The aim of this study was therefore to
      evaluate the dynamic changes in LSMs during the course of acute hepatic
      inflammation. MATERIAL AND METHODS: Thirty-one patients with acute hepatitis A
      (AHA) were enrolled in this study (mean +/- SD age 29 +/- 7 years; 32.3% male).
      Only AHA patients who visited our hospital before their alanine aminotransferase
      (ALT) levels peaked were included. The day when AHA-associated symptoms began was
      considered as Day 0. Serum levels of ALT and bilirubin (BIL), and the
      international normalized ratio (INR) were measured every 2 days, as were LSMs,
      until the peak levels of all parameters were identified. Subsequently, these
      parameters were measured every 1-2 weeks until they had normalized. RESULTS: Peak
      serum levels of ALT and BIL, the INR, and LSMs were 3723 +/- 1513 IU/l, 5.8 +/-
      2.4 mg/dl, 1.3 +/- 0.3, and 11.9 +/- 5.7 kPa, respectively. The time taken for
      LSMs to peak from Day 0 (8 +/- 2 days) differed significantly from that for ALT
      (5 +/- 1 days), BIL (10 +/- 4 days), and INR (5 +/- 1 days). LSMs had normalized
      (< or = 5.5 kPa) in all patients at 34 +/- 17 days after Day 0. ALT level and the
      INR were significantly associated with peak LSMs and BIL level and the INR with
      the time taken for normalization of LSMs. CONCLUSIONS: LSMs changed dynamically
      during the course of AHA. The pattern of change appears to be related to the
      severity of hepatic necroinflammation.

PMID- 20059405
TI  - Gastrointestinal symptoms, quality of life and bone mineral density in mild
      enteropathic coeliac disease: a prospective clinical trial.
AB  - OBJECTIVE: The diagnosis of coeliac disease requires small-bowel mucosal villous
      atrophy with crypt hyperplasia. However, patients with endomysial antibodies but
      structurally normal villi may suffer from a disorder similar to those with
      villous atrophy. The aim of this study was to evaluate gastrointestinal symptoms,
      quality of life and bone mineral density in patients with mild enteropathy, and
      the effect of a gluten-free diet. MATERIAL AND METHODS: A prospective trial was
      carried out in 73 adults having endomysial antibodies with normal villous
      morphology (Marsh I-II; mild enteropathy) or villous atrophy (Marsh III).
      Gastrointestinal symptoms and quality of life were surveyed by means of
      structured questionnaires and bone mineral density by means of X-ray
      absorptiometry. Altogether, 110 subjects served as non-coeliac controls. RESULTS:
      At baseline, patients with mild enteropathy evinced more gastrointestinal
      symptoms than non-coeliac controls, but there were no significant differences in
      quality of life between the groups. After 1 year on a gluten-free diet,
      indigestion and depression were significantly alleviated in the mild enteropathy
      group. Osteoporosis or osteopenia was detected in 58% of subjects in the mild
      enteropathy group and there was a trend towards improved bone mineral density
      after the treatment. CONCLUSIONS: Endomysial antibody-positive patients with
      normal villous structure may suffer from gastrointestinal symptoms and have poor
      bone health. Furthermore, they benefit from a gluten-free diet similar to those
      with overt villous atrophy.

PMID- 20059406
TI  - Giant cell arteritis and bilateral peroneal nerve palsy.

PMID- 20059407
TI  - The star chart to Ta bladder cancer: an unsophisticated analysis of two
      dimensional gel electrophoresis proteome maps.
AB  - OBJECTIVE: To explore the use of two-dimensional gel electrophoresis (2DE) for
      analysing the proteome of clinically relevant tissue samples such as biopsies
      from transurethral resections of the bladder (TURB), by generating a Ta proteome
      map, possibly identifying technical or biological artefacts, and searching for
      biological subgroups associated with clinical data. MATERIAL AND METHODS:
      Biopsies from 23 patients were homogenized and the protein content was separated
      by 2DE. The gels were silver stained and scanned, and the resulting pictures were
      analysed for similarities in the spot pattern. RESULTS: A majority of 18 patients
      displayed a consistent protein expression profile and a Ta proteome map was
      constructed by averaging the grey value of each pixel in all 18 pictures. Spot
      detection was performed on a project proteome map (based on all 23 samples) and
      resulted in 1583 detected spots. 416 of these which were positively detected in
      all 18 "Ta-map" samples. Three patients displayed a pattern with some marked
      alterations to the majority profile, possibly artefacts of yet unknown heredity.
      One patient revealed a protein pattern deemed to constitute a separate group,
      later revealed as a blinded control from a T4 tumour. Only one sample was sparse
      in protein spots, probably containing mostly blood owing to inadequate sampling.
      No biological subgroups associated with clinical data were identified.
      CONCLUSIONS: A Ta proteome map was successfully created from TURB samples.
      Deviating protein expression profiles were identified, indicating a future
      potential to reveal biologically relevant subgroups in this or other stages of
      urothelial cell carcinomas.

PMID- 20059408
TI  - Correlations between enuresis in children and nocturia in mothers.
AB  - OBJECTIVE: To demonstrate a relationship between enuresis and nocturia. MATERIAL
      AND METHODS: The study investigated 250 mothers (average age 34.6 +/- 3.3 years)
      whose children attended the Department of Pediatrics of the Second University of
      Naples because they suffered from enuresis. Data were collected by self-reported
      questionnaire and personal interview. All women provided written informed consent
      with guarantees of confidentiality. Both the presence of nocturia in adulthood
      and enuresis in childhood were taken into account. RESULTS: The overall
      prevalence of nocturia was 38% (n = 95). There was a history of childhood
      bedwetting in eight mothers (5%) without nocturia and in 61 mothers (65%) with
      nocturia; the difference was significant (chi(2) p < 0.01). Moreover, among the
      110 enuretic children of nocturic mothers, 69 (62%) suffered from non
      monosymptomatic nocturnal enuresis (NMNE), and 34 (56%) of their mothers suffered
      from NMNE in childhood. Nocturic mothers suffering from non-monosymptomatic
      enuresis during their childhood had offspring with a higher risk of developing
      non-monosymptomatic enuresis (odds ratio 4.3 95%, confidence interval 2.6-7.1, p
      < 0.01). CONCLUSIONS: These findings enabled a close connection between nocturia
      in adulthood and enuresis in childhood to be hypothesized. Furthermore, this
      analysis provided evidence of the link between suffering from nocturia, and
      previously from enuresis, and having children affected by enuresis.

PMID- 20059409
TI  - Letter to the editor: re: "Influence of recombinant human platelet-derived growth
      factor on lateral ridge augmentation using biphasic calcium phosphate and guided
      bone regeneration: a histomorphometric study in dogs".

PMID- 20059411
TI  - Letter to the editor: periodontal conditions in Werner syndrome.

PMID- 20059412
TI  - The effect of photodynamic therapy for periodontitis: a systematic review and
      meta-analysis.
AB  - BACKGROUND: The purpose of this review was to evaluate the effectiveness of
      photodynamic therapy (PDT) for periodontitis in adults as a primary mode of
      treatment or as an adjunct to non-surgical treatment of scaling and root planing
      (SRP) compared to a conventional non-surgical SRP treatment. METHODS: MEDLINE,
      EMBASE, CINAHL, other relevant databases, and the International Pharmaceutical
      Abstracts were searched from their inception until May 2009 for randomized
      controlled trials of PDT compared to a placebo, no intervention, or non-surgical
      treatment in an adult population. Data on changes in clinical attachment level
      (CAL), probing depth, gingival recession, and full-mouth plaque or bleeding
      scores were extracted and meta-analyzed, and the pooled mean difference (MD) was
      reported. RESULTS: Five studies were included in this review. These studies had a
      small sample size for some of the performed analysis with a moderate to high risk
      of biases. There were clinical heterogeneities among included studies. PDT as an
      independent treatment or as an adjunct to SRP versus a control group of SRP did
      not demonstrate statistically or clinically significant advantages. Combined
      therapy of PDT + SRP indicated a probable efficacy in CAL gain (MD: 0.34; 95%
      confidence interval [CI]: 0.05 to 0.63) or probing depth reduction (MD: 0.25 mm;
      95% CI: 0.04 to 0.45 mm). CONCLUSIONS: PDT as an independent treatment or as an
      adjunct to SRP was not superior to control treatment of SRP. Therefore, the
      routine use of PDT for clinical management of periodontitis cannot be
      recommended. Well-designed clinical trials are needed for proper evaluation of
      this therapy.

PMID- 20059413
TI  - Microbiologic testing and outcomes of full-mouth scaling and root planing with or
      without amoxicillin/metronidazole in chronic periodontitis.
AB  - BACKGROUND: It has been suggested that use of systemic antibiotics should be
      limited to patients with specific microbiologic profiles. The main purpose of the
      present analysis was to study whether microbiologic testing before therapy was of
      value in predicting which patients would specifically benefit from adjunctive
      amoxicillin and metronidazole, given in the context of full-mouth scaling and
      root planing (SRP) within 48 hours. METHODS: This was a 6-month, single-center,
      double-masked, placebo-controlled, randomized longitudinal study. Fifty-one
      patients received full-mouth periodontal debridement, performed within 48 hours;
      then, 25 subjects received metronidazole, 500 mg, and amoxicillin, 375 mg, three
      times a day for 7 days, and 26 received a placebo (control group). Pooled
      microbiologic samples were taken from the deepest pocket at baseline in each
      quadrant before and 6 months after treatment. Six periodontal pathogens were
      quantified by real-time polymerase chain reaction. RESULTS: Forty-seven patients
      were followed for 6 months. After treatment, test subjects had a substantially
      lower mean number of persisting sites with probing depth >4 mm and bleeding on
      probing than did control subjects (0.4 versus 3.0; P = 0.005; month 6).
      Aggregatibacter actinomycetemcomitans (previously Actinobacillus
      actinomycetemcomitans) could not be detected in the antibiotic group after
      treatment. However, in the placebo group, three of six subjects positive for A.
      actinomycetemcomitans continued to be positive. Lower frequencies were also noted
      in the test group for Porphyromonas gingivalis (P = 0.013) and Tannerella
      forsythia (previously T. forsythensis) (P = 0.007). However, even subjects
      testing negative for A. actinomycetemcomitans at baseline had a significantly
      better primary clinical outcome if they received the active drugs. The presence
      of six putative periodontal pathogens (A. actinomycetemcomitans, Fusobacterium
      nucleatum spp., P. gingivalis, Prevotella intermedia, Treponema denticola, and T.
      forsythia) quantified prior to therapy was not correlated with the outcome of
      full-mouth SRP with or without amoxicillin and metronidazole. CONCLUSION:
      Excellent clinical results in the antibiotics group were obtained regardless of
      the presence or absence of six classic periodontal periopathogens prior to
      treatment.

PMID- 20059414
TI  - Adipokines and inflammatory mediators after initial periodontal treatment in
      patients with type 2 diabetes and chronic periodontitis.
AB  - BACKGROUND: This study was performed to evaluate the effects of initial
      periodontal treatment on clinical periodontal measurements, glycemic control, and
      systemic inflammatory mediator levels in patients with type 2 diabetes and
      chronic periodontitis. METHODS: Thirteen well-controlled (glycated hemoglobin
      [HbA1c] <7%) and 12 poorly controlled (HbA1c > or =7%) patients with type 2
      diabetes and chronic periodontitis and 15 systemically healthy patients with
      chronic periodontitis were enrolled. Blood samples were collected at baseline
      from all patients and 1 and 3 months after the initial periodontal treatment from
      patients with diabetes. Serum levels of tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6, C-reactive protein (CRP), soluble intercellular adhesion
      molecule-1, adiponectin, and leptin were analyzed by enzyme-linked immunosorbent
      assay. RESULTS: The study groups showed similar improvements in clinical
      periodontal variables at all evaluation times (P <0.05). HbA1c levels in the
      poorly controlled group with diabetes decreased significantly at 3 months after
      completion of the initial periodontal treatment (P <0.05), whereas no significant
      changes were evident in the well-controlled group. There were insignificant
      decreases in TNF-alpha and CRP levels (P >0.05). IL-6 levels decreased in well
      controlled patients with diabetes and in the systemically healthy group (P
      <0.05). Adiponectin levels increased in the systemically healthy group (P <0.05).
      Leptin levels increased at 1 month in well-controlled patients with diabetes (P
      <0.05). CONCLUSIONS: Within the limits of this study, patients with type 2
      diabetes and chronic periodontitis exhibited similar clinical periodontal
      improvements as their systemically healthy counterparts. Initial periodontal
      treatment appeared to improve glycemic control in poorly controlled patients with
      diabetes. Decreases in levels of IL-6, TNF-alpha, CRP, and leptin and an increase
      in adiponectin levels after periodontal therapy may be a function of glycemic
      control in patients with type 2 diabetes.

PMID- 20059415
TI  - Esthetic index for anterior maxillary implant-supported restorations.
AB  - BACKGROUND: The aim of this study is to develop and validate a complex esthetic
      index (CEI) designed for rating the esthetics of anterior maxillary implant
      supported restorations with respect to the surrounding soft and hard tissues.
      METHODS: Fifty patients (31 males and 19 females; age: 18 to 50 years; mean age
      +/- SD: 32.4 +/- 9.1 years) previously treated with dental implants were
      evaluated regarding the esthetic results of their restorations using the proposed
      CEI. Two calibrated oral surgeons did the evaluation and recording. The
      evaluation was carried out twice by each of the examiners 2 weeks apart. The
      weighted Cohen's kappa was used to calculate the intra- and interobserver
      agreement. RESULTS: An analysis of CEI for 50 anterior maxillary implant
      supported restorations showed good intra- and interobserver agreement for the
      soft tissue index (S) and implant-supported restoration index (R). Only the
      interobserver agreement for the overall R was rated as moderate (0.54 and 0.52).
      The single-parameter analysis showed that the lowest (moderate) intra- and
      interobserver agreement was with the subjective parameters of S (soft tissue
      color and texture variations) and R (crown surface roughness and ridges and color
      and translucency). An adequate CEI of S100, P100, and R100 was scored by both
      examiners in 10% and 12% of cases for evaluations I and II, respectively.
      CONCLUSIONS: This study presents evidence that this newly developed CEI, which
      incorporates the implant restoration and adjacent soft and hard tissue
      parameters, is a reproducible tool for scoring anterior implant esthetic
      predictably. However, prospective clinical trials involving examiners with
      different training backgrounds are needed to further validate the long-term
      stability of this index.

PMID- 20059416
TI  - Accuracy of two stereolithographic guide systems for computer-aided implant
      placement: a computed tomography-based clinical comparative study.
AB  - BACKGROUND: Stereolithographic surgical guides provide significant benefits
      during the simultaneous placement of multiple implants with regard to the final
      prosthetic plan. However, deviation from the planning poses a significant risk.
      Deviations of implants that were placed by bone-, tooth-, and mucosa-supported
      stereolithographic surgical guides were examined in this study. METHODS: After
      enrolling 54 eligible patients, 294 implants were planned on cone-beam
      computerized tomography CB(CT)-derived images. Sixty guides, both single- and
      multiple-type, were produced using two commercial systems. Mucosa-supported
      guides were fixed with osteosynthesis screws. Implants were inserted, and at the
      end of osseointegration period, a new CB(CT) scan was performed. Preoperative
      planning was merged with the new CB(CT) data to identify the deviations between
      the planned and placed implants for each support type and manufacturer. The
      Kruskal-Wallis and Mann-Whitney U tests were used for comparison (P <0.05).
      RESULTS: There were no damage-related complications in any critical anatomy.
      Implants that were placed by bone-supported guides had the highest mean
      deviations (5.0 degrees +/- 1.66 degrees angular, and 1.70 +/- 0.52 mm and 1.99
      +/- 0.64 mm for implant shoulder and tip, respectively), whereas the lowest
      deviations were measured in implants that were placed by mucosa-supported guides
      (2.9 degrees +/- 0.39 degrees angular, and 0.7 +/- 0.13 mm and 0.76 +/- 0.15 mm
      for implant shoulder and tip, respectively). CONCLUSIONS: Computer-aided planning
      and manufacturing surgical guides in accordance with CB(CT) images may help
      clinicians place implants. Rigid screw fixation of a single guide incorporating
      metal sleeves and a special drill kit further minimizes deviations.

PMID- 20059417
TI  - Site-specific gingival bleeding on probing in a steady-state plaque environment:
      influence of polymorphisms in the interleukin-1 gene cluster.
AB  - BACKGROUND: We previously reported a high prevalence of a combination of alleles
      2 at positions interleukin (IL)-1A(-889) and IL-1B(+3954) in an Arabic population
      with gingivitis. In a steady state, the proportion of sites with bleeding on
      probing (BOP) was consistently reduced. The aim of the present study is to expand
      this observation by considering the site level. METHODS: Fifty healthy non
      smoking volunteers, 19 to 28 years of age, participated in this study. Clinical
      examinations included probing depth, BOP, plaque index (PI), and calculus.
      Examinations were repeated after 2 and 4 weeks, and subjects were advised not to
      change oral hygiene habits. Polymorphisms in the IL-1 gene cluster were assessed
      using a reverse hybridization assay. RESULTS: Twenty-six subjects (52%) carried
      alleles 2 at positions IL-1A(-889) and IL-1B(+3954) and were designated genotype
      positive. In multivariate multilevel models of BOP, bleeding tendency in subjects
      with positive IL-1 genotype was only reduced at sites with PI 0 (odds ratio of
      0.98, 0.65, and 0.56 at baseline and 2 and 4 weeks, respectively; chi(2)((3)) =
      11.946; P = 0.008) or 1 (chi(2)((3)) = 6.027; P = 0.110). A decreased bleeding
      tendency at certain tooth types in subjects who were IL-1 positive was largely
      related to the relative cleanliness of these areas. Random parts of the models
      revealed very low biserial correlations of 0.13 to 0.15 at the site level,
      whereas correlations were considerably higher (0.76 to 0.83) at the subject
      level. CONCLUSION: Multilevel modeling of site-specific data yielded new
      information about the influence of the IL-1 genotype in plaque-induced
      gingivitis.

PMID- 20059418
TI  - Association of single nucleotide gene polymorphism at interleukin-1beta +3954, 
      511, and -31 in chronic periodontitis and aggressive periodontitis in Dravidian
      ethnicity.
AB  - BACKGROUND: Interleukin (IL)-1beta gene polymorphisms are considered a potential
      risk factor for periodontal disease. The aim of this study is to identify the
      association of IL-1beta gene polymorphisms with chronic periodontitis and
      aggressive periodontitis in a Malayalam-speaking Dravidian population from South
      India. METHODS: The case-control study consisted of 43 patients with chronic
      periodontitis and 54 patients with aggressive periodontitis as cases, and the
      control group consisted of 101 healthy subjects. All subjects were genotyped for
      IL-1beta +3954, -511, and -31 loci by polymerase chain reaction amplification
      followed by restriction enzyme digestion and gel electrophoresis. Genotype,
      allele, and haplotype analyses were done. RESULTS: Analyses for allele and
      genotypes showed a high frequency of the C allele and CC genotype for single
      nucleotide polymorphism IL-1beta +3954 in the group with chronic periodontitis
      and no difference for patients with aggressive periodontitis compared to controls
      (P <0.05). Haplotype analysis showed that IL-1beta -31 and -511 were in strong
      linkage disequilibrium in all groups. The IL-1beta -31 allele T was in linkage
      with allele T of IL-1beta +3954 in the control group. CONCLUSIONS: In the
      Malayalam-speaking Dravidian population, allele C of IL-1beta +3954 appeared to
      be an important risk factor for chronic periodontitis. The IL-1beta -31 allele T
      was in linkage with allele T of IL-1beta +3954 in the control group. No gene
      polymorphisms were found in patients with aggressive periodontitis. More studies
      with a larger sample size involving the entire cluster of the IL-1beta gene are
      necessary to determine the exact role of IL-1beta gene polymorphisms in
      periodontal disease.

PMID- 20059419
TI  - Biologic width and morphologic characteristics of soft tissues around immediately
      loaded implants: studies performed on human autopsy specimens.
AB  - BACKGROUND: Esthetics and the health of oral implants are based upon the soft
      tissue reaction and biologic width (BW). METHODS: Twelve dental implants were
      placed in the maxilla and mandible of a patient who smoked. Permanent standard
      abutments and temporary restorations were immediately fixed in place during the
      surgery stage. The definitive restorations were placed 4 months after loading
      without removal of the original abutments. After 10 months, the patient died, and
      the implants were removed en block and processed for histology. RESULTS: The BW
      in the maxilla was 6.5 +/- 2.5 mm, whereas in the mandible, it was 4.8 +/- 1.3 mm
      (P = 0.017). The sulcular epithelium (SE) in the maxilla was 2.7 +/- 0.8 mm,
      whereas in the mandible, it was 1.7 +/- 0.4 mm (P <0.001). The junctional
      epithelium (JE) in the maxilla was 1.3 +/- 0.4 mm, whereas in the mandible, it
      was 1.5 +/- 0.5 mm (P = 0.164). The connective tissue (CT) in the maxilla was 2.5
      +/- 1.3 mm, whereas in the mandible, it was 1.6 +/- 0.4 mm (P = 0.006). In the
      maxillary bone, the BW, SE, and CT were significantly longer than in the
      mandible, whereas for the JE, no statistically significant difference was
      observed. CONCLUSION: The soft tissue organization around dental implants was
      different for upper and lower jawbones.

PMID- 20059420
TI  - Subgingival plaque removal using a new air-polishing device.
AB  - BACKGROUND: The purpose of this study is to evaluate the safety, patient
      acceptance, and short-term microbiologic effect of a new air-polishing device in
      subjects in maintenance care with residual pockets > or =5 mm. METHODS: This was
      an examiner-masked, randomized, split-mouth clinical trial. A new disposable
      nozzle, allowing the subgingival application of amino acid glycine powder at a
      limited pressure, was compared to scaling and root planing (SRP) in 50 subjects
      with residual pockets during the maintenance phase. After removing supragingival
      deposits, the spray was applied for 4 to 5 seconds in all sites > or =5 mm in the
      test quadrant, whereas SRP was used in the control quadrant. Microbiologic
      samples were taken from one treated test and one control site 2 days before and 7
      days after treatment. Total bacterial counts and the counts of six periodontal
      pathogens were determined by real-time polymerase chain reaction. RESULTS: No
      adverse event was noted in any subject for the test or control treatment. Using a
      visual analog scale, the patients perceived the test treatment to be
      significantly less painful/uncomfortable than the hand instrumentation (P
      <0.001). Significantly less time was used by the operator for the test procedure
      (P <0.001). The reduction in bleeding on probing was significant for the treated
      sites in the test and control quadrants (P = 0.019 and P <0.001, respectively),
      but traditional SRP reduced the bleeding tendency significantly more than air
      polishing (P = 0.045). The differences in the total bacterial load and the counts
      of six periodontal pathogens between the test and control sites did not reach
      statistical significance. The longitudinal reduction was significant in control
      sites for total bacteria load (P <0.001), Porphyromonas gingivalis (P = 0.01),
      Treponema denticola (P <0.001), and Tannerella forsythia (previously T.
      forsythensis) (P <0.001). CONCLUSION: Subgingival air polishing with a new device
      was safe (no adverse events were noted), perceived to be more acceptable by the
      patients, and was more time-efficient than SRP; however, on a microbiologic
      level, it was not superior to conventional SRP.

PMID- 20059421
TI  - Relationships among gingival crevicular fluid biomarkers, clinical parameters of
      periodontal disease, and the subgingival microbiota.
AB  - BACKGROUND: The objectives of this study were to measure levels of gingival
      crevicular fluid (GCF) biomarkers and subgingival bacterial species in
      periodontally healthy subjects and subjects with periodontitis to explore the
      relationships among these biomarkers, the subgingival microbiota, and the
      clinical parameters of periodontal disease. METHODS: Clinical periodontal
      parameters were measured at six sites per tooth in 20 subjects with periodontitis
      and 20 periodontally healthy subjects. GCF and subgingival plaque samples were
      obtained from the mesio-buccal aspect of every tooth. GCF levels of interleukin
      (IL)-1beta and IL-8 and matrix metalloproteinase 8 were measured using
      checkerboard immunoblotting, and the levels of 40 bacterial taxa were quantified
      using checkerboard DNA-DNA hybridization. A subset of "clinically healthy" sites
      from each group was analyzed separately. The significance of the differences
      between groups was determined using the unpaired t test or the Mann-Whitney test.
      Correlations among immunologic, microbiologic, and clinical data were determined
      using the Spearman rank correlation coefficient. RESULTS: There were positive
      correlations among mean clinical parameters, mean levels of the three biomarkers,
      and the proportions of orange and red complex species (P <0.05). Clinically
      healthy sites from subjects with periodontitis had higher levels of IL-1beta and
      IL-8 and higher proportions of orange and red complex species (P <0.05) than
      clinically healthy sites from periodontally healthy subjects. Red complex species
      were positively associated with the expression of all biomarkers (P <0.05),
      whereas purple and yellow complex species had negative correlations with IL-1beta
      and IL-8 (P <0.05). CONCLUSIONS: Clinically healthy sites from subjects with
      periodontitis have higher levels of GCF biomarkers and periodontal pathogens than
      clinically healthy sites from periodontally healthy subjects. Different microbial
      complexes demonstrated distinct associations with specific GCF biomarkers.

PMID- 20059422
TI  - Proinflammatory gene expression at chronic periodontitis and peri-implantitis
      sites in patients with or without type 2 diabetes.
AB  - BACKGROUND: Diabetes and periodontal diseases are often associated. Both have
      highly inflammatory components, but the role played by distinct phlogistic
      mediators in their pathogenesis is not fully understood and remains
      controversial. The purpose of this study is to evaluate whether type 2 diabetes
      alters the expression of inflammatory mediators in sites with chronic
      periodontitis (CP) or peri-implantitis (P-IM). METHODS: The expression of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-6 and -8, and monocyte chemotactic
      protein (MCP)-1 plus key CC chemokine receptors (CCR1 through 5) and CXC
      chemokine receptors (CXCR1 through 3) was quantified by real-time polymerase
      chain reaction (PCR) in gingival or peri-implant biopsies from 135 patients with
      well-controlled or poorly controlled diabetes and periodontal disease, 65
      patients with periodontal disease but otherwise healthy, and 90 systematically
      and periodontally healthy subjects. Western blots were performed. RESULTS:
      Relative to controls, in patients without diabetes and patients with well
      controlled diabetes, TNF-alpha, CCR5, and CXCR3 expression was exclusively higher
      in sites with P-IM (P <0.01), whereas IL-6 and -8 were overexpressed in sites
      with CP and, even more, in sites with P-IM (P <0.01). In patients with poor
      glycemic control, TNF-alpha, CCR5, and CXCR3 mRNAs were increased in sites with
      CP (P <0.01). A statistically significant higher IL-6 and -8 expression from
      patients without diabetes and patients with well-controlled diabetes was observed
      compared to patients with poorly controlled diabetes. Regardless of
      metabolic/glycemic status, MCP-1 and CCR2 and 4 were markedly higher in both of
      the oral pathologies examined (P <0.01). At the protein levels, Western blot
      experiments confirmed the real-time PCR results. CONCLUSIONS: These findings
      showed that: 1) in subjects without diabetes and patients with well-controlled
      diabetes, TNF-alpha, CCR5, and CXCR3 may constitute distinctive biomarkers of P
      IM; 2) poor glycemic control abolished the differences between CP and P-IM
      regarding the expression of these mediators; and 3) type 2 diabetes affected the
      expression of TNF-alpha, IL-6 and -8, CCR5, and CXCR3.

PMID- 20059423
TI  - Nitric oxide synthase in gingival tissues of patients with chronic periodontitis
      and with and without diabetes.
AB  - BACKGROUND: The purpose of this study was to evaluate the expression of inducible
      nitric oxide synthase (iNOS) in the gingival tissues of periodontitis patients
      with and without type 2 diabetes to assess whether NO plays a role in the
      severity of periodontitis in patients with diabetes. Patients with diabetes and
      healthy patients were used as controls. METHODS: A total of 80 patients were
      evaluated in four groups (with 20 subjects each): patients with chronic
      periodontitis and diabetes (12 males and eight females; mean age, 52.1 +/- 6.9
      years), patients with chronic periodontitis who were otherwise healthy (12 males
      and eight females; mean age, 43.1 +/- 8.9 years), periodontally healthy patients
      with diabetes (12 males and eight females; mean age 50.9 +/- 6.3 years), and
      systemically and periodontally healthy control subjects (12 males and eight
      females; mean age 29.8 +/- 9.2 years). Periodontal parameters were recorded.
      Immunohistochemistry was used to detect inflammation and iNOS expression in
      gingival tissues. RESULTS: Although periodontal parameters were slightly higher
      in periodontitis compared to diabetic periodontitis, immunohistochemical
      parameters were higher in diabetic periodontitis compared to periodontitis. All
      periodontal parameters were higher in patients with periodontitis and
      with/without diabetes compared to controls and patients with diabetes. All
      immunohistochemical parameters were higher in patients with diabetes and
      periodontitis compared to patients with only diabetes or periodontitis, but there
      was no difference between the latter two groups. There was a correlation between
      the expression of iNOS and inflammatory cells in controls, patients with
      diabetes, and patients with periodontitis but not in patients with diabetes and
      periodontitis. CONCLUSIONS: Inflammation and iNOS expression were more prominent
      in the gingiva of the patients with both diabetes and periodontitis. However,
      iNOS expression did not seem to have an additional detrimental effect on the
      course of periodontitis in patients with diabetes compared to those with
      periodontitis alone.

PMID- 20059424
TI  - Evaluation of stress induced by implant type, number of splinted teeth, and
      variations in periodontal support in tooth-implant-supported fixed partial
      dentures: a non-linear finite element analysis.
AB  - BACKGROUND: This study investigated the biomechanical interactions in tooth
      implant-supported fixed partial dentures (FPDs) with variations in periodontal
      support, implant system, number of splinted teeth, and load type using the non
      linear finite element (FE) approach. METHODS: The section contours of the
      alveolar bone, abutment teeth, and prosthesis were acquired using computed
      tomography (CT) and micro-CT to construct the FE models with normal periodontal
      support (NPS) and compromised periodontal support (CPS) containing one- and two
      piece implants splinted to the first and second premolars. Realistic interface
      conditions within the implant system were simulated using frictional contact
      elements. The main effects for each level of investigated factors in terms of
      stress values and dissimilar mobility of natural teeth and the implant were
      computed for all models. RESULTS: Analytic results indicated that the load
      condition was the predominant factor affecting stress developed in the implant,
      bone, and prosthesis. Additionally, the oblique occlusal forces increased the
      stress values relative to that of axial analogs. A splinted system with a two
      piece implant increased stress on the bone and decreased stress on the prosthesis
      compared to that of the one-piece implant. The splinted system with a CPS only
      slightly increased implant stress on the bone compared to that of the splint
      system with NPS. Splinting an additional tooth did not significantly impact
      stress values for the tooth-implant-supported FPD. CONCLUSIONS: A one-piece
      structure implant may be better than that of a two-piece structure implant in
      decreasing bone stress when a natural tooth is planned to connect with an
      implant. The factors of periodontal support and number of splinted teeth only
      slightly influenced stress in tooth-implant-supported FPDs.

PMID- 20059425
TI  - In vitro killing activity of crevicular concentrations of tinidazole plus common
      oral antibiotics against high-density mixed inocula of periodontal pathogens in
      strict anaerobic conditions.
AB  - BACKGROUND: Odontogenic infections are polymicrobial. This study explores the in
      vitro killing activity by concentrations similar to those found in crevicular
      fluid of tinidazole in combination with amoxicillin/clavulanic acid, clindamycin
      and levofloxacin against four groups of high-density mixed inocula of anaerobes
      (Prevotella buccae, Fusobacterium nucleatum, and Veillonella spp.) and
      facultative (Capnocytophaga spp. and Streptococcus spp.) isolates of periodontal
      pathogens. METHODS: Killing curves were assessed under strict anaerobic
      conditions with antibiotics alone and in combination with tinidazole at
      concentrations similar to those achieved in crevicular fluid against
      approximately 10(7) colony forming units (CFU)/ml inoculum (1:1:1:1:1 proportion
      of the five bacterial isolates) of the four bacterial groups. Group 1 did not
      include beta-lactamase-producing strains; groups 2, 3, and 4 included one, two,
      and three beta-lactamase-producing strains, respectively. RESULTS: In single-drug
      experiments, at 48 hours, tinidazole alone did not show significant killing of
      the entire bacterial population, whereas reductions in the initial inocula > or
      =2.09 log(10) CFU/ml with clindamycin, > or =3.26 log(10) CFU/ml with
      amoxicillin/clavulanic acid, and > or =3.83 log(10) CFU/ml with levofloxacin were
      obtained. When combined with tinidazole, reductions were significantly higher for
      all antibiotics: > or =5.28 log(10) CFU/ml with clindamycin, > or =4.78 log(10)
      CFU/ml with amoxicillin/clavulanic acid, and > or =6.17 log(10) CFU/ml with
      levofloxacin. CONCLUSION: In addition to its high activity against anaerobic
      periodontal pathogens, tinidazole offered synergism with other antibiotics
      against the large strict anaerobic subpopulation and the small facultative
      subpopulation of a high-density mixed inocula of odontogenic pathogens under
      strict anaerobic conditions, similar to those of odontogenic infections.

PMID- 20059426
TI  - Osteogenesis in an in vitro coculture of human periodontal ligament fibroblasts
      and human microvascular endothelial cells.
AB  - BACKGROUND: Periodontal bone healing is a complex process involving many cells
      and processes that must function flawlessly for proper healing to occur. The
      exact progenitor cells that contribute to this process are not fully
      characterized. Periodontal fibroblasts and pericytes were postulated to be
      potential osteoprogenitor cells. This study describes a viable coculture model
      for the in vitro study of osteogenesis. METHODS: Human microvascular endothelial
      cells (HMVEC) and human periodontal ligament (HPDL) fibroblasts were cocultured
      in a layered model and monitored for the development of runt-related
      transcription factor 2 (runx2) and desmin expression by real-time polymerase
      chain reaction. Conditions shown to be osteogenic (bone morphogenetic protein
      [BMP]-2 and enamel matrix derivative [EMD]) were compared to a control coculture
      that was unstimulated. RESULTS: The HMVEC migrated into a layer of collagen
      containing only HPDL cells as monitored by fluorescent labeling. runx2 and desmin
      expressions were increased in stimulated cocultures in week 2 compared to
      controls. At week 3, the unstimulated control cocultures developed the expression
      of runx2 and desmin, and the cocultures that were stimulated with EMD and BMP-2
      achieved significantly higher levels of these factors than any of the other
      conditions. CONCLUSIONS: Signs of osteogenesis were present in the cocultures in
      unstimulated and stimulated conditions. However, in the stimulated condition,
      osteogenic markers were increased at earlier time points. As such, this model may
      provide a good method for the study of specific cellular processes that may lead
      to osteogenesis and eventually for understanding the regeneration of periodontal
      bone in vivo.

PMID- 20059427
TI  - Dietary-induced hyperparathyroidism affects serum and gingival proinflammatory
      cytokine levels in rats.
AB  - BACKGROUND: Poor diet and inadequate nutrition are suggested to affect the
      periodontium as well as impair the systemic health. This study investigated the
      systemic and periodontal effects of dietary-induced hyperparathyroidism (dHPT) by
      evaluating serum and gingival proinflammatory cytokine levels. METHODS: Twenty
      four Sprague-Dawley rats were used in the study. dHPT was induced in 12 rats by
      calcium/phosphorus imbalance, and 12 rats were fed a standard diet (SD).
      Afterward, endotoxin-induced periodontitis was induced on the right mandibular
      molar teeth (mmt). Four study groups were created: dHPT + mmt without
      periodontitis (group 1), dHPT + mmt with periodontitis (group 2), SD + mmt with
      periodontitis (group 3), and SD + mmt without periodontitis (group 4).
      Interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) levels were
      measured by enzyme-linked immunosorbent assay to evaluate the proinflammatory
      cytokine profiles. Serum cytokines were analyzed in the blood samples collected
      prior to periodontitis induction, whereas gingival cytokines were analyzed in the
      gingival supernatants of the four groups. RESULTS: Serum cytokines were higher in
      dHPT rats than in SD rats (P <0.001), with a positive correlation between
      parathormone and the cytokines (P <0.001). Gingival cytokines were highest in
      group 2 and lowest in group 4 (group 2 > group 3 > group 1) (P <0.001). There was
      a positive correlation between parathormone and the gingival cytokines in group 1
      (P <0.001 for IL-1beta; P <0.01 for TNF-alpha). CONCLUSION: The results suggested
      that increased serum proinflammatory cytokine production may be a complication of
      dHPT, and this may affect healthy and diseased periodontia by increasing gingival
      proinflammatory cytokine levels.

PMID- 20059428
TI  - Transcrestal sinus floor elevation with a minimally invasive technique.
AB  - BACKGROUND: Recently, we proposed a minimally invasive technique to limit the
      postoperative morbidity of transcrestal sinus floor elevation procedures. The
      technique is based on the use of specially designed drills and osteotomes. The
      purpose of the present study is to present data on the clinical outcomes and
      postoperative morbidity of sinus floor elevation procedures performed using the
      proposed technique. METHODS: Fourteen implants were placed in the posterior
      portions of the maxilla areas of 11 patients using the proposed technique.
      Postoperative pain and discomfort were assessed using a 100-mm visual analog
      scale (VAS). The incidences of intra- and postoperative complications were
      recorded. The position of the grafted sinus floor with respect to the implant
      apex was assessed on periapical radiographs 6 months post-surgery. RESULTS: The
      augmented sites had a presurgery residual bone height of 6.1 mm, whereas the mean
      length of the implants inserted in augmented sites was 10.3 +/- 0.9 mm.
      Immediately after surgery, VAS scores for pain and discomfort were 9.4 +/- 13.4
      and 17.0 +/- 22.2, respectively. The 7-day VAS score for pain was 2.1 +/- 4.9. No
      complications were observed during or after the surgical procedure. Six months
      after surgery, a newly formed mineralized tissue was found at or beyond the level
      of the implant apex in all cases. CONCLUSION: The proposed technique represents a
      suitable option to elevate the sinus floor due to a predictable displacement of
      the sinus floor and a limited post-operative morbidity.

PMID- 20059429
TI  - The effect of piezoelectric use on open sinus lift perforation: a retrospective
      evaluation of 56 consecutively treated cases from private practices.
AB  - BACKGROUND: The lateral window approach to maxillary sinus augmentation is a well
      accepted treatment option in implant dentistry. The most frequent complication
      reported with traditional techniques has been the perforation of the Schneiderian
      membrane, with perforation rates ranging from 11% to 56%. The purpose of this
      retrospective, consecutive case series from two private practices was to report
      on the rate of Schneiderian membrane perforations and arterial lacerations when a
      piezoelectric surgical unit was used in conjunction with hand instrumentation to
      perform lateral window sinus elevations. METHODS: Clinical data (Schneiderian
      membrane perforation, Underwood septa, and laceration of the lateral arterial
      blood supply to the maxillary sinus) were obtained retrospectively from two
      private practices and pooled for analysis. The information was collated after an
      exhaustive chart review. Fifty-six consecutively treated lateral window sinus
      lifts were performed on 50 partially or completely edentate patients. RESULTS:
      Zero perforations of the Schneiderian membrane occurred during the piezoelectric
      preparation of the lateral antrostomies, whereas two perforations were noted
      during subsequent membrane elevations using hand instrumentation. In both
      instances, membrane perforations were associated with sinus septa. The overall
      sinus perforation rate was 3.6%. Arterial branches of the posterior superior
      alveolar artery were encountered in 35 cases, and there were zero instances of
      arterial laceration. CONCLUSIONS: This retrospective case series from clinical
      private practices confirmed that a lateral window approach to sinus elevation
      incorporating piezoelectric technology in conjunction with hand instrumentation
      was an effective means to achieve sinus elevation while minimizing the potential
      for intraoperative complications. Further prospective and randomized controlled
      studies are warranted to qualify these observations.

PMID- 20059430
TI  - Spontaneous pigmentation of non-pigmented palatal tissue after periodontal
      surgery.
AB  - BACKGROUND: A 22-year-old African American female was referred for augmentation
      of keratinized gingiva around implants at the right and left maxillary second
      premolar sites. Presurgical evaluation revealed generalized melanosis of the
      buccal gingiva and a lack of keratinized tissue around implants at sites #4 and
      #13. No pigmentation was noted on the palatal tissues. METHODS: Thick free
      gingival grafts were harvested bilaterally from the non-pigmented palate and
      secured to the recipient sites with bioabsorbable sutures. Hemostasis was
      achieved at the palatal donor sites with moistened gauze, and an acrylic stent
      was delivered for patient comfort. RESULTS: Both palatal donor sites healed with
      spontaneous pigmentation. The pigmentation intensified with time but resulted in
      no adverse outcome. CONCLUSIONS: Post-surgical healing in patients with gingival
      pigmentation is not entirely predictable, as multiple studies have demonstrated
      widely inconsistent results in regards to gingival pigmentation upon healing.
      When performing periodontal plastic surgery in patients with pigmented oral
      tissues, it is important to discuss all possible outcomes, including spontaneous
      pigmentation.

PMID- 20059431
TI  - A systematic performance evaluation of brain and body temperature sensors using
      ultra-stable temperature references.
AB  - The impact of a rise in the temperature of the human brain in patients who have
      suffered cerebral damage is not completely understood. Current studies are
      ambiguous; some show that a high brain temperature, and others a low brain
      temperature, is an indicator of poor prognosis. The reported effect is often very
      subtle, at the <0.5 degrees C level, and this may be due to the performance, or
      even the location of the temperature sensor. This study investigates the first of
      these issues, i.e. the performance of the sensor. Here performance validation is
      undertaken for three commonly used temperature sensors for brain and body
      temperature measurement, using ultra-stable temperature references. At body
      temperature all three sensor types performed within manufacturer's
      specifications. Given that only a small number of temperature sensors were
      tested, the indication is that, provided the sensors are located correctly, the
      small observed differences in temperature are real - though the issue of clinical
      significance is still to be addressed.

PMID- 20059432
TI  - Mild stimulation in assisted reproduction.
AB  - The conventional ovarian stimulation protocols currently applied have several
      drawbacks arising from the intense ovarian stimulation and from the high
      financial cost. Recently, new concepts such as mild stimulation and friendly in
      vitro fertilisation have rapidly acquired great popularity among infertile
      patients although the medical world is still reluctant to apply these protocols
      generally. We have observed that although with soft stimulation fewer oocytes are
      retrieved, pregnancy rates are not affected if more than five oocytes are
      obtained in the follicular aspiration. Another important issue is the additional
      value of the embryo cryopreservation programmes that will result in cumulative
      pregnancy rates no different from those obtained with conventional protocols. The
      benefits of combining these mild stimulation protocols with a selective reduction
      of the number of embryos to replace have helped us in reducing the incidence of
      multiple pregnancies and the global cost of the treatment.

PMID- 20059433
TI  - Premature pubarche in Mediterranean girls: high prevalence of heterozygous CYP21
      mutation carriers.
AB  - AIM: This study investigated the prevalence and consequences of heterozygous
      CYP21A2 mutations in premature pubarche (PP) girls. MAIN FINDING: We investigated
      36 French Mediterranean girls with isolated PP. We performed synacthen testing
      with 17OHP and 21-deoxycortisol evaluation, along with molecular analysis of the
      CYP21A2 gene in girls with abnormal elevation of one of these two adrenal
      steroids. Three girls (8.3%) had nonclassical adrenal hyperplasia, secondary to
      compound heterozygosity that associated at least one severe mutation for the
      three girls. A heterozygous mutation of the CYP21A2 gene was confirmed by
      molecular biology in eight girls (22%); a deletion of the CYP21A2 gene was found
      in one of them. Biological hyperandrogenism was found in the prepubertal CYP21A2
      mutation carriers, whereas the four heterozygous girls who were followed long
      enough to have reached pubertal age presented biological and clinical
      hyperandrogenism. CONCLUSIONS: We underline the high prevalence of heterozygous
      CYP21A2 mutations in girls with PP and demonstrate the usefulness of systematic
      screening by synacthen testing, both to improve their future clinical management
      and to prevent the transmission of classical adrenal hyperplasia to future
      offspring. Because of the severe metabolic and cardiovascular consequences of
      hyperandrogenism, long-term follow-up of these heterozygous patients is
      mandatory.

PMID- 20059434
TI  - The psychosomatic character of clinical governance.

PMID- 20059435
TI  - The effect of male body mass index on sperm parameters.
AB  - Overweight and obese men have been reported to have lower sperm quality. The aim
      of this study was to evaluate, whether body mass index (BMI) is related to
      changes in semen parameters. In a cross-sectional study, sperm parameters were
      reviewed in 852 normal, healthy men, of reproductive age (25-50). BMI was divided
      into four groups: underweight, normal, overweight and obese. Sperm concentration
      of overweight and obese men were 63 and 62, respectively, which were lower than
      subjects with normal BMI (71). Total sperm count and sperm motility in overweight
      and obese men were significantly lower than men with normal BMI too. Sperm
      morphology in study groups was similar. The results revealed a significant
      inverse correlation between the BMI and the sperm parameters.

PMID- 20059436
TI  - Increased occurrence of marked elevations of lipoprotein(a) in ageing,
      hypercholesterolaemic men with low testosterone.
AB  - OBJECTIVE: We previously examined the inverse relationship between total serum
      testosterone (T) and the occurrence of the metabolic syndrome in ageing men using
      baseline data from two lipid treatment studies. We further examined baseline data
      from a subset of US men participating in one of these two studies to assess the
      relationship between T and the cardiovascular risk factor lipid, lipoprotein(a)
      [Lp(a)]. METHODS: Baseline T, lipid, glycaemic and anthropometric data were
      obtained from 107 men (mean age: 55 years). Inclusion criteria included low
      density lipoprotein cholesterol > or = 3.4-4.9 mmol/l and triglycerides < or =
      4.0 mmol/l. Baseline Lp(a) levels were examined across the following baseline T
      subgroups: <15 nmol/l (low/low-normal T) and > or = 15 nmol/l (normal T).
      RESULTS: There was an overall trend for a higher incidence of clinically
      significant Lp(a) elevations in men with low T; 17.1% of men in the low/low
      normal T subgroup had an Lp(a) level > or = 3 times the upper limit of normal
      compared to 8.1% in the normal T subgroup. CONCLUSIONS: The data from this
      descriptive analysis suggest that ageing men with low serum T levels may have an
      increase in marked elevations in Lp(a), which would be expected to be associated
      with a significant increase in their cardiovascular event risk.

PMID- 20059437
TI  - Glycosylated hemoglobin level in the second trimester predicts birth weight and
      amniotic fluid volume in non-diabetic pregnancies with abnormal screening test.
AB  - OBJECTIVE: To investigate relationship between glycemic control in first half of
      pregnancy by measuring mid-pregnancy HbA1c and neonatal birth weight and amniotic
      fluid volume. METHODS: We prospectively enrolled 220 pregnant women who received
      oral glucose tolerance test (OGTT) after positive gestational diabetes mellitus
      screening. We included 102 women with normal OGTT results into final analysis. We
      measured birth weight and amniotic fluid index (AFI) at 32-34 weeks. RESULTS:
      Mean birth weight was 3313+/-426 g, and 15.7% of neonates were classified as
      large-for-gestational age (LGA). Mean Hb1Ac was 4.96+/-0.28%. Median AFI was 145
      mm, and polyhydramnios rate was 2.9%. Birth weight was positively correlated with
      HbA1c level (r=0.373, p<0.001) and pre-pregnancy body mass index (BMI; r=0.351,
      p<0.001). Linear regression analysis showed that HbA1c and pre-pregnancy BMI were
      positive independent determinants of neonatal birth weight, and HbA1c was
      positive independent determinant of AFI. Receiver operating characteristics curve
      identified HbA1c level of 4.99 as optimal threshold for prediction of LGA with
      93.8% sensitivity, 61.6% specificity and positive likelihood ratio (+LR) of 2.45
      and pre-pregnancy BMI value of 25.2 as optimal threshold for prediction of LGA
      with 81.3% sensitivity, 57% specificity and +LR of 1.9. CONCLUSION: In non
      diabetic pregnant women with abnormal screening test, mid-pregnancy HbA1c level
      and pre-pregnancy BMI may predict neonatal birth weight. AFI in 32-34 weeks of
      gestation is related with mid-pregnancy HbA1c level.

PMID- 20059438
TI  - Low potassium level during the first half of pregnancy is associated with lower
      risk for the development of gestational diabetes mellitus and severe pre
      eclampsia.
AB  - OBJECTIVE: To examine the association between potassium level during the first
      half of pregnancy and the development of gestational diabetes mellitus (GDM) and
      hypertensive disorders in the second half of the pregnancy. METHODS: The study
      population included all registered births between the years 2001-2007. The
      potassium levels during the first half of pregnancy were sorted by the following
      groups: K < 3.5 mEq/l; K = 3.5-3.99 mEq/l; and K > or = 4 mEq/l. The linear by
      linear chi(2)-test was used to determine the association between potassium level
      during the beginning of pregnancy and pregnancy complications. RESULTS: The study
      population included 8114 deliveries. A significant linear association was
      documented between potassium level in the first half of the pregnancy and the
      prevalence of GDM in the second half of the pregnancy: 6.3% in the K < 3.5 mEq/l
      group, 6.6% in the K = 3.5-3.99 mEq/l group and 8.2% in the K > 4 mEq/l group; (p
      = 0.008). A statistically significant for lower rates of severe pre-eclampsia was
      noted between the groups: 0.4% in the K < 3.5 mEq/l group, 0.9% in the K = 3.5
      3.99 mEq/l group, 1.3% in the K = 4.0-4.99 mEq/l group and 1.5% in the K > or = 5
      mEq/l group, (p = 0.027). Indeed, K > 5 mEq/l was noted as a significant risk
      factor for both, severe pre-eclampsia and for GDM. Using two multiple logistic
      regression models controlling for maternal age, potassium level was noted as an
      independent risk factor for both GDM and severe pre-eclampsia. CONCLUSIONS: High
      potassium levels during the first half of pregnancy are associated with higher
      risk for the development of GDM and severe pre-eclampsia.

PMID- 20059439
TI  - Outcomes for fetal echogenic bowel during the second trimester ultrasound.
AB  - OBJECTIVE: To investigate the association between fetal echogenic bowel (FEB)
      during the second trimester and perinatal outcome. METHODS: A retrospective chart
      review of FEB during the second trimester over 3 years. RESULTS: A total of 56
      women were identified of 9067 screened (0.6%) women. Forty-seven agreed to
      genetic counseling (84%). Of those, 22 (39%) agreed to an amniocentesis. There
      were three cases of trisomy 21, one case of trisomy 18 and one case of fetal CMV
      infection. Twelve fetuses had an adverse outcome (21%), with only three of them
      having an echogenic bowel as the only finding. CONCLUSIONS: In our study, almost
      80% of the fetuses had an uncomplicated perinatal outcome. FEB was present as the
      only finding in only 5% of the fetuses with an adverse outcome. A potential
      association with placental abnormalities and a low prevalence of viral infections
      was observed. These findings may be of use in counseling parents.

PMID- 20059440
TI  - Diabetes mellitus and the risk of preterm birth with regard to the risk of
      spontaneous preterm birth.
AB  - INTRODUCTION: It is internationally agreed that diabetes mellitus (DM) is
      associated with increased maternal and fetal morbidity and long-term
      complications. To avoid these complications, it is often necessary to induce
      birth before term. The impact of DM on spontaneous preterm birth (spontaneous
      labor, preterm premature rupture of membranes and/or cervical incompetence
      resulting in delivery before the completion of 37 gestation weeks) is still
      unexplained. Preterm birth accounts for the most neonatal deaths and infant
      morbidities, and therefore it still remains one of the biggest challenges in
      obstetrics. OBJECTIVE: Our study determined if there is an increasing tendency
      towards spontaneous preterm birth in mothers with gestational and preexisting DM.
      METHODS: In this retrospective cohort study, 187 pregnant women with gestational
      DM and preexisting DM were compared to a randomized control group consisting of
      192 normoglycemic women concerning gestational age and perinatal outcome. Data
      were collected by the Medical University of Vienna. Multiple pregnancies and
      women with severe maternal diseases, such as preeclampsia, were excluded.
      RESULTS: Women with DM tended significantly more often to preterm births (P =
      0.002). A significant difference in the incidence of spontaneous preterm birth
      was found (P = 0.047). CONCLUSION: DM affects the length of gestation and
      incidence of spontaneous preterm birth.

PMID- 20059441
TI  - Timing of umbilical cord clamping: new thoughts on an old discussion.
AB  - The optimal time to clamp the umbilical cord in preterm and full-term neonates
      after birth continues to be a matter of debate. A review of randomised controlled
      trials comparing the effects of early versus late cord clamping on maternal and
      infant outcomes was performed to assess data in favor of immediate or delayed
      clamping. Although there is no conclusive evidence, delayed cord clamping seems
      to be beneficial in preterm and full-term neonates without compromising the
      initial postpartum adaptation phase or affecting the mother in the short term.
      However, further randomised clinical studies are needed to confirm the benefits
      of delayed cord clamping.

PMID- 20059442
TI  - Plasma visfatin levels in pregnant women with normal glucose tolerance,
      gestational diabetes and pre-gestational diabetes mellitus.
AB  - OBJECTIVE: Visfatin, an adipocytokine, is a peptide predominantly expressed in
      and secreted from visceral adipose. In this study, we aimed to compare visfatin
      levels in gestational (GDM) and pre-gestational diabetic (pre-GDM) women with
      healthy pregnant women. We also sought to determine whether there was a
      correlation between visfatin levels and serum glucose levels at 1 h after the 50
      g oral glucose challenge test in pregnant women with GDM and normal glucose
      tolerance. METHODS: The study consisted of 65 pregnant women: 21 patients with
      GDM (Group 1), 20 patients with pre-GDM (Group 2) and 24 gestational age and BMI
      matched healthy pregnant women (Group 3) were enrolled. RESULTS: Plasma visfatin
      levels in Groups 1 and 2 were significantly higher than in Group 3 (P < 0.001).
      Plasma visfatin levels in Groups 1 and 2 were similar (P > 0.05). There was no
      significant correlation between visfatin levels and serum glucose levels at 1 h
      after the glucose tolerance test in both Groups 1 and 3 (P > 0.05). CONCLUSIONS:
      Our results support the literature indicating higher visfatin levels in women
      with GDM compared to women with normal glucose tolerance. Interestingly, we found
      similarly high visfatin levels in women with pre-GDM.

PMID- 20059443
TI  - History of abortion and perinatal outcomes associated with preeclampsia in
      nulliparous Japanese women.
AB  - The purpose of the present study was to examine the influence of history of
      abortion on the next pregnancy outcomes associated with preeclampsia. This
      investigation involved 5206 nulliparous Japanese women with singleton pregnancies
      who delivered after 22 weeks of gestation. The patients were divided into two
      groups: those with a history of spontaneous and/or artificial abortion during the
      previous pregnancies after the marriage with the same partner
      (n&#x2009;=&#x2009;1029) and those without a history of abortion
      (n&#x2009;=&#x2009;4173). There was no significant difference in the incidence of
      preeclampsia between the 2 groups with and without previous abortions (4.0% vs.
      3.9%, p&#x2009;=&#x2009;0.91). In addition, there were no significant differences
      in the incidence of perinatal complications associated with preeclampsia between
      the 2 groups. Although further studies may be needed, based on the current
      results history of abortion does not seem to affect perinatal outcomes associated
      with preeclampsia.

PMID- 20059444
TI  - Maternal overweight and pregnancy outcome in women with Type-1 diabetes mellitus
      and different degrees of nephropathy.
AB  - OBJECTIVE: We aimed to assess the parameters associated with complicated
      pregnancy in women with Type 1 diabetes mellitus (DM) and nephropathy. STUDY
      DESIGN: A cohort study of 46 consecutive women diagnosed with Type 1 DM with
      nephropathy prior to pregnancy was included during the years 2000-2007.
      Complicated pregnancy was defined as one or more of the following: first
      trimester abortion, superimposed pre-eclampsia, pre-term delivery <34 weeks,
      small and large for gestational age neonate, macrosomia, admission to the
      neonatal intensive care unit and foetal loss (after 22 weeks' gestation).
      RESULTS: Overall, 31/46 (67%) had at least one pregnancy complication. Body mass
      index (BMI) was the only parameter with a significant difference between the
      groups, being higher in the women with complicated pregnancy vs. uncomplicated
      pregnancy (27 +/- 9 vs. 24 +/- 3, p = 0.027). On Multiple logistic regression
      model in which composite outcome (pregnancy complication) as the dependent
      variable, pre-pregnancy BMI was the only statistically significant parameter with
      a difference between the groups (p = 0.044). No statistical difference was found
      between the groups in the rate of pre-pregnancy counselling (60% vs. 67%),
      glycaemic control prior to pregnancy (Hba1c 7.5 vs. 7.1%), the prevalence of
      patients achieving desired level of glycaemic control (44% vs. 42%), weight gain
      during pregnancy (12.4 vs. 10.6 kg), duration of DM (18.0 vs. 19.7 years) and
      proportion of patients treated with angiotensin converting enzyme inhibitors
      prior to pregnancy (26 vs. 33%). CONCLUSION: Overweight is associated with poor
      pregnancy outcome in patients with Type-1 DM and different degrees of
      nephropathy.

PMID- 20059445
TI  - The hyperglycemia and adverse pregnancy outcome (HAPO) study: can we use the
      results as a basis for change?
AB  - At present the diagnosis of gestational diabetes uses differing criteria in
      different parts of the world, with none being based on pregnancy outcome.
      Different glucose loads (50, 75 or 100 grams) are recommended, rather than the
      standard 75 gram load utilized worldwide in nonpregnant individuals. The HAPO
      study was designed to determine what level of glucose intolerance, short of
      diabetes, is associated with an excess of adverse perinatal outcomes. On a 75
      gram, 2-hour OGTT each of the 3 values is significantly and continuously related
      to various adverse outcomes, and no inflection point is evident. Consequently an
      international group of interested experts is developing recommendations for
      diagnostic criteria for GDM which, it is hoped, will be adopted world wide.

PMID- 20059446
TI  - Bronchoalveolar lavage and response to cyclophosphamide in scleroderma
      alveolitis.
AB  - OBJECTIVES: Systemic sclerosis (SSc) is characterized by abnormal fibrosis of the
      skin and internal organs, particularly the lungs. Recent reports have revealed a
      lack of correlation between bronchoalveolar lavage (BAL) variations and response
      to cyclophosphamide (CYC) in patients with scleroderma-related alveolitis. Our
      study aimed to evaluate whether the normalization of BAL cellularity correlates
      with long-term response to CYC. METHODS: We retrospectively studied 26
      consecutive SSc patients with alveolitis diagnosed by BAL and treated with CYC
      therapy (cumulative dosage 26.5 +/- 11.7 g; 21.1 +/- 8.9 months of treatment). We
      evaluated high-resolution computed tomography (HRCT), forced vital capacity
      (FVC), and carbon monoxide diffusing capacity (DLCO) variations before and after
      CYC. Radiological and functional parameters were re-evaluated in 23 patients
      after 1-year follow-up. RESULTS: BAL cellularity normalized after CYC therapy in
      12/26 (46.2%) patients (group 1), while it remained abnormal in 14/26 (53.8%)
      (group 2). FVC and DLCO of group 1 slightly increased after CYC (p = 0.014 and p
      = 0.07, respectively) and remained stable at follow-up, whereas in group 2 they
      did not change after CYC and at follow-up (p = not significant). Moreover, at the
      end of CYC, FVC and/or DLCO showed a clinical improvement/stabilization in all
      patients of group 1 versus 8/14 of group 2, while at the re-evaluation 1 year
      after completing CYC, 2/11 patients of group 1 worsened versus 5/12 of group 2.
      HRCT progression was observed in 1/11 of group 1 and 8/12 of group 2 (p = 0.009).
      CONCLUSIONS: BAL fluid normalization after CYC therapy correlated with long-term
      response to treatment, contrary to what is observed in individuals with
      persistent alveolitis.

PMID- 20059447
TI  - Bone mineral content in young adults with active or inactive juvenile idiopathic
      arthritis and in controls.
AB  - OBJECTIVE: To obtain information on bone mineral content (BMC) in juvenile
      idiopathic arthritis (JIA) in young adulthood. METHODS: BMC measurements of 116
      young adults with JIA and controls were performed at the lumbar spine and the
      proximal femur by dual-energy X-ray absorptiometry (DXA). RESULTS: Patients were
      divided into the JIA-active group (n = 73) and the JIA-inactive group (n = 43).
      Fifty-five per cent of men and 30% of women had their disease in remission. Forty
      eight per cent in the JIA-active group and 16% in the JIA-inactive group had used
      glucocorticoids (p < 0.001). Mean BMC in the femoral neck was 5.76 (SD 0.21) g
      for men and 4.74 (SD 0.10) g for women in the JIA-active group; 5.84 (SD 0.23) g
      for men and 4.59 (SD 0.06) g for women in the JIA-inactive group; and 6.65 (SD
      0.20) g for men and 4.78 (SD 0.07) g for women in the controls. Both JIA groups
      had lower BMC values in the femoral neck than the controls (p < 0.001), but a
      statistically significant difference was found among men (p = 0.006). There was
      no significant difference in mean BMC in the lumbar spine between the JIA groups
      and the controls, nor between men and women. Glucocorticoid use, weight and also
      height among women were associated statistically significantly with BMC in the
      femoral neck. CONCLUSIONS: Young adults, especially men, with JIA have reduced
      BMC values in the femoral neck. Glucocorticoid use and weight, but not disease
      activity, seem to be associated with lower BMC. However, osteoporosis is rare.

PMID- 20059448
TI  - Treatment of concomitant prolapse and stress urinary incontinence via a
      transobturator subvesical mesh without independent suburethral tape.
AB  - OBJECTIVE: Evaluate the efficacy of a transobturator subvesical mesh for
      cystocele in concomitant stress urinary incontinence (SUI). DESIGN: Longitudinal
      observational study. SETTING: Tertiary referral urogynecology center. POPULATION:
      One hundred and five women with at least an anterior vaginal wall prolapse and
      concomitant SUI who underwent surgery. METHODS: After reduction of prolapse
      elements, the intervention consisted of a non-absorbable monoprosthesis placement
      with two transobturator expansions and, if necessary, associated hysterectomy or
      infraccocygeal sacropexy. No specific procedure was performed for SUI. MAIN
      OUTCOME MEASURES: All patients had a physical examination and a subjective
      symptoms assessment via questionnaire in the preoperative period and at one-year
      or more after surgery. The pelvic organ prolapse quantification system was used
      for anatomical results. For SUI, Ingelman-Sundberg classification and cough test
      were used. Loss of urine was measured by a one-hour pad test. Functional results
      were evaluated by visual analog scale, quality-of-life questionnaires, including
      the pelvic floor distress inventory and the pelvic floor impact questionnaire.
      RESULTS: Median follow-up was 45 months (range: 12-72). A total of 102 women
      (97%) were cured of their prolapse, of whom 72 (69%) were cured of their SUI and
      13 (12%) showed improvement. Pad test, visual analogic scale and quality-of-life
      questionnaires were all improved (p < 0.05). Complications consisted of one
      rectal injury, one transitory urinary retention, and two hematomas. Of the
      erosions 6% was observed for monofilament polypropylene prostheses. CONCLUSION:
      Transvaginal monoprosthesis for the simultaneous correction of prolapse and SUI
      represents an effective treatment for bulky or recurrent prolapse as well as
      posthysterectomy vaginal vault prolapse.

PMID- 20059449
TI  - Impact of catheter insertion using the radial approach on vasodilatation in
      humans.
AB  - The aim of this study was to determine the impact of catheter sheath insertion, a
      model of endothelium disruption in humans, on the conventional FMD (flow-mediated
      dilatation) response in vivo. Seventeen subjects undergoing transradial
      catheterization were recruited and assessed prior to, the day after, and 3-4
      months postcatheterization. The catheter sheath's external diameter was 2.7 mm,
      and the average preprocedure internal radial artery diameter was 2.8 mm,
      indicating a high likelihood of endothelial denudation as a consequence of sheath
      placement. Radial artery flow-mediated and endothelium-derived NO (nitric oxide)
      dependent function (FMD) was assessed within the region of sheath placement
      (sheath site) and also above the sheath (catheter site). GTN (glyceryl
      trinitrate) endothelium-independent NO-mediated function was also assessed
      distally. Measurements were made in both arms at all time points; the non
      catheterized arm provided an internal control. Neither sheath (4.5+/-0.9%) nor
      catheter (4.4+/-0.9%) insertion abolished FMD, although both significantly
      decreased FMD from preintervention levels (9.0+/-0.8% sheath segment; 8.4+/-0.8%
      catheter segment; P<0.05). The impact of sheath and catheter placement on FMD was
      no longer evident after approximately 3 months recovery (8.0+/-1.5 and 8.1+/
      1.7%, sheath and catheter, respectively). GTN responses also decreased from
      14.8+/-1.7 to 7.9+/-1.0% (P<0.05) as a result of sheath placement, but values
      returned to baseline at approximately 3 months (13.0+/-1.8%). These results
      suggest that the presence of an intact, functional endothelial layer and
      consequent NO release may not be obligatory for some component of the FMD
      response. This raises the possibility of an endothelium-independent contribution
      to the flow-induced vasodilatation in humans.

PMID- 20059450
TI  - Developmental and cellular functions of the ESCRT machinery in pluricellular
      organisms.
AB  - ESCRTs (endosomal sorting complexes required for transport) were first discovered
      in yeast and are known to be required in the biogenesis of the MVB
      (multivesicular body). Most ESCRT research has been carried out in vitro using
      models such as yeast and mammalian cells in culture. The role of the ESCRTs genes
      in endosome maturation is conserved from yeast to mammals, but little is known
      about their function during development in multicellular organisms. Since ESCRTs
      play a leading role in regulating some cell signalling pathways by addressing
      receptors to the lysosome, it appears important to monitor ESCRT functions in
      multicellular models. The present review summarizes recent research on the
      developmental and cellular functions of the ESCRT in Caenorhabditis elegans,
      Drosophila melanogaster, Mus musculus or Arabidopsis thaliana.

PMID- 20059451
TI  - Your paper has been accepted for publication.

PMID- 20059452
TI  - Antipsychotic prescribing trends: a review of pharmaco-epidemiological studies.
AB  - OBJECTIVE: To review findings from pharmaco-epidemiological studies exploring
      antipsychotic (AP) drugs prescribing trends. METHOD: We retrieved original
      studies that explored AP prescribing trends in general population samples since
      2000. For each study, we extracted information on sampling method, period,
      assessment of AP use and corresponding estimates (incidence rates, prevalence
      rates, pharmacy sales, prescription data) and diagnostic assessment. RESULTS:
      Nearly all studies meeting the inclusion criteria (n = 17) showed an increase in
      AP prescriptions, mainly because of a dramatic rise in second-generation
      antipsychotics (SGAP) prescriptions. APs are often prescribed for non-psychotic
      disorders in adults as well as in children and adolescents. CONCLUSION:
      Considering the growing number of persons from the general population exposed to
      APs, population studies assessing the risk/benefit ratio of SGAP use in disorders
      other than psychosis are necessary, particularly in children and adolescents.

PMID- 20059453
TI  - The prefrontal cortex: a target for antipsychotic drugs.
AB  - OBJECTIVE: At therapeutic doses, classical antipsychotic drugs occupy a large
      proportion of subcortical dopamine D2 receptors, whereas atypical antipsychotics
      preferentially occupy cortical 5-HT(2) receptors. However, the exact cellular and
      network basis of their therapeutic action is not fully understood. METHOD: To
      review the mechanism of action of antipsychotic drugs with a particular emphasis
      on their action in the prefrontal cortex (PFC). RESULTS: The PFC controls a large
      number of higher brain functions altered in schizophrenia. Histological studies
      indicate the presence of a large proportion of PFC neurons expressing
      monoaminergic receptors sensitive to the action of atypical- and to a lesser
      extentclassical antipsychotic drugs. Functional studies also indicate that both
      drug families act at PFC level. CONCLUSION: Atypical antipsychotic drugs likely
      exert their therapeutic activity by a preferential action on PFC neurons, thus
      modulating the PFC output to basal ganglia circuits. Classical antipsychotics
      also interact with these PFC targets in addition to blocking massively striatal
      D2 receptors.

PMID- 20059454
TI  - Fahr's disease - a model of neuropsychiatric illness with cognitive and psychotic
      symptoms.

PMID- 20059455
TI  - Irritability in depression can be a symptom of mixed depression.

PMID- 20059457
TI  - Attention-deficit/hyperactivity disorder and co-varying aggression - a
      relationship with serotonin-dependent impulsive and physiological trait
      moderators?

PMID- 20059462
TI  - Apolipoprotein e4 allele and recurrent pregnancy loss: larger samples are still
      needed.

PMID- 20059464
TI  - Toll-like receptor signaling and pre-eclampsia.
AB  - Systemic inflammation and abnormal/poor placentation represent hallmarks of pre
      eclampsia. Accumulating evidence suggests that infectious agents might increase
      the risk of pre-eclampsia; the innate immune defense mechanisms may interact with
      pro-inflammatory pathways, and contribute to the development of pre-eclampsia.
      The evidence for this has been supported by indirect epidemiologic and clinical
      studies, as well as by some direct support from experimental studies. Recent data
      directly implicate signaling by Toll-like receptors in the pathogenesis of pre
      eclampsia, and establish a crucial link between pre-eclampsia and defense against
      both foreign pathogens and endogenously generated inflammatory ligands. Here, we
      review the rapid progress in this field, which has improved our understanding of
      the interplay between pathogen invasion, innate immune defense mechanisms, and
      pre-eclampsia.

PMID- 20059466
TI  - STAT3 polymorphisms linked with idiopathic recurrent miscarriages.
AB  - PROBLEM: We investigated the association of signal transducers and activators of
      transcription (STAT)3 gene variants with idiopathic recurrent miscarriage (RM).
      METHOD OF STUDY: A case-control study involving 189 RM patients and 244 control
      women was carried out. STAT3 (rs1053004 and rs1023023) genotyping was performed
      by allelic discrimination/real-time PCR method. RESULTS: STAT3 rs1053004 C allele
      [OR (95% CI) = 1.60 (1.22-2.10)] and C/C genotype [OR (95% CI) = 3.42 (1.70
      6.92)] were positively associated with RM. Two-locus (rs1053004/rs1053023)
      haplotype analysis revealed increased frequency of CG and CA haplotypes in RM
      patients, of which only CA haplotype (Pc = 0.020) remained positively associated
      with RM after applying the Bonferroni correction. This was confirmed by
      multivariate regression analysis (OR = 1.70; 95% CI = 1.17-2.46) after adjusting
      for a number of covariates. CONCLUSION: STAT3 rs1053004 variant is significantly
      associated with idiopathic RM. Replication studies on other racial groups and
      other STAT3 gene variants are warranted.

PMID- 20059465
TI  - Inflammation and implantation.
AB  - Approximately half of all human embryo implantations result in failed pregnancy.
      Multiple factors may contribute to this failure, including genetic or metabolic
      abnormalities of the embryo. However, many of these spontaneous early abortion
      cases are attributed to poor uterine receptivity. Furthermore, although many
      fertility disorders have been overcome by a variety of assisted reproductive
      techniques, implantation remains the rate-limiting step for the success of the in
      vitro fertilization (IVF) treatments. It has been demonstrated that endometrial
      biopsies performed either during the spontaneous, preceding cycle, or during the
      IVF cycle itself, significantly improve the rate of implantation, clinical
      pregnancies and live births. These observations suggest that mechanical injury of
      the endometrium may enhance uterine receptivity by provoking the immune system to
      generate an inflammatory reaction. In strong support of this idea, we recently
      found that dendritic cells (DCs), an important cellular component of the innate
      immune system, play a critical role in successful implantation in a mouse model.
      In this review, we discuss the hypothesis that the injury-derived inflammation in
      the biopsy-treated patients generates a focus for uterine DCs accumulation that,
      in turn, enhances the endometrial expression of essential molecules, which
      facilitate the interaction between the embryo and the uterine epithelium.

PMID- 20059467
TI  - Isolation of non-activated monocytes from human umbilical cord blood.
AB  - PROBLEM: Methods for monocyte purification are common but few work with umbilical
      cord monocytes that do not activate the cell for subsequent culture analysis.
      METHODS OF STUDY: The collection procedure avoids use of needles and procedures
      that variably activate blood clotting and uses a purification procedure that
      involves diluted Ficoll, autologous serum to remove platelets and 42% and 51%
      Percoll step gradients for the final purification. The resulting monocytes were
      stimulated with bacterial lipopolysaccharide and formalin-treated bacteria
      Escherichia coli and group B streptococci (GBS) to secrete TNF-alpha and IL
      1beta, measured by ELISA. RESULTS: The purification procedure results in non
      active but stimulation-competent monocytes with high yields (2.3-9 x 10(7) cells)
      and purity (from 70% to 98%). CONCLUSION: We describe a procedure that is easy,
      uses common reagents and provides a uniformly high yield and purity of non
      activated fetal monocytes for studies of innate defense responses.

PMID- 20059470
TI  - Epidemiological approach to identifying genetic predispositions for atypical
      hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) is caused by several susceptibility
      genes. A registry including analyses of susceptibility genes, familial occurrence
      and genotype-phenotype correlation should provide classification insights.
      Registry data of 187 unrelated index patients included age at onset, gender,
      family history, relapse of aHUS and potentially triggering conditions. Mutation
      analyses were performed in the genes CFH, CD46 and CFI and in the six potential
      susceptibility genes, FHR1 to FHR5 and C4BP. Germline mutations were identified
      in 17% of the index cases; 12% in CFH, 3% in CD46 and 2% in CFI. Twenty-nine
      patients had heterozygous mutations and one each had a homozygous and compound
      heterozygous mutation. Mutations were not found in the genes FHR1-5 and C4BP. In
      40% of the patients with familial HUS a mutation was found. Penetrance by age 45
      was 50% among carriers of any mutation including results of relatives of mutation
      positive index cases. The only risk factor for a mutation was family history of
      HUS (p = 0.02). Penetrance of aHUS in carriers of mutations is not complete.
      Occurrence of homo- and heterozygous mutations in the same gene suggests that the
      number of necessary DNA variants remains unclear. Among clinical information only
      familial occurrence predicts a mutation.

PMID- 20059469
TI  - Interaction between fibrinogen and IL-6 genetic variants and associations with
      cardiovascular disease risk in the Cardiovascular Health Study.
AB  - The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen
      synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and
      subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We
      investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen
      concentrations, carotid intima-media thickness, and myocardial infarction or
      ischemic stroke in 3900 European-American Cardiovascular Health Study
      participants. To identify combinations of genetic main effects and interactions
      associated with outcomes, we used logic regression. We also evaluated whether the
      relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level
      using linear regression models with multiplicative interaction terms.
      Combinations of fibrinogen and IL6 SNPs were significantly associated with
      fibrinogen level (p < 0.005), but not with other outcomes. Fibrinogen levels were
      higher in individuals having FGB1437 (rs1800790) and lacking FGA6534 (rs6050)
      minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen
      level. Marginally significant (p= 0.03) interactions between IL-6 level and FGA
      and FGG promoter SNPs associated with fibrinogen levels were detected. We
      identified potential gene-gene interactions influencing fibrinogen levels.
      Although IL-6 responsive binding sites are present in fibrinogen gene promoter
      regions, we did not find strong evidence of interaction between fibrinogen SNPs
      and IL6 SNPs or levels influencing CVD.

PMID- 20059468
TI  - The transcriptome of the fetal inflammatory response syndrome.
AB  - PROBLEM: The fetal inflammatory response syndrome (FIRS) is considered the
      counterpart of the systemic inflammatory response syndrome (SIRS), but
      similarities in their regulatory mechanisms are unclear. This study characterizes
      the fetal mRNA transcriptome of peripheral leukocytes to identify key biological
      processes and pathways involved in FIRS. METHOD OF STUDY: Umbilical cord blood
      from preterm neonates with FIRS (funisitis, plasma IL-6 >11 pg/mL; n = 10) and
      neonates with no evidence of inflammation (n = 10) was collected at birth.
      Results Microarray analysis of leukocyte RNA revealed differential expression of
      541 unique genes, changes confirmed by qRT-PCR for 41 or 44 genes tested. Similar
      to SIRS and sepsis, ontological and pathway analyses yielded significant
      enrichment of biological processes including antigen processing and presentation,
      immune response, and processes critical to cellular metabolism. RESULTS: are
      comparable with microarray studies of endotoxin challenge models and pediatric
      sepsis, identifying 25 genes across all studies. CONCLUSION: This study is the
      first to profile genome-wide expression in FIRS, which demonstrates a substantial
      degree of similarity with SIRS despite differences in fetal and adult immune
      systems.

PMID- 20059471
TI  - Different evolutionary histories of the coagulation factor VII gene in human
      populations?
AB  - Immoderate blood clotting constitutes a risk factor for cardiovascular disease in
      modern industrialised societies, but is believed to have conferred a survival
      advantage, i.e. faster recovery from bleeding, on our ancestors. Here, we
      investigate the evolutionary history of the Coagulation Factor VII gene (F7) by
      analysing five cardiovascular-risk-associated mutations from the F7 promoter and
      nine neutral polymorphisms (six SNPs and three microsatellites) from the flanking
      region in 16 populations from the broader Mediterranean region, South Saharan
      Africa and Bolivia (687 individuals in total). Population differentiation and
      selection tests were performed and linkage disequilibrium patterns were
      investigated. In all samples, no linkage disequilibrium between adjacent F7
      promoter mutations -402 and -401 was observed. No selection signals were detected
      in any of the samples from the broader Mediterranean region and South Saharan
      Africa, while some of the data suggested a potential signal of positive selection
      for the F7 promoter in the Native American samples from Bolivia. In conclusion,
      our data suggest, although do not prove, different evolutionary histories in the
      F7 promoter region between Mediterraneans and Amerindians.

PMID- 20059472
TI  - Frequency of the AGT Pro11Leu polymorphism in humans: Does diet matter?
AB  - The Pro11Leu substitution in the AGXT gene, which causes primary hyperoxaluria
      type 1, is found with high frequency in some human populations (e.g., 5-20% in
      Caucasians). It has been suggested that this detrimental mutation could have been
      positively selected in populations with a meat-rich diet. In order to test this
      hypothesis, we investigated the occurrence of Pro11Leu in both herder and
      agriculturalist populations from Central Asia. We found a lower frequency of this
      detrimental mutation in herders, whose diet is more meat-rich, as compared to
      agriculturalists, which therefore challenges the universality of the previous
      claim. Furthermore, when combining our original data with previously published
      results, we could show that the worldwide genetic differentiation measured at the
      Pro11Leu polymorphism does not depart from neutrality. Hence, the distribution of
      the variation observed in the AGXT gene could be due to demographic history,
      rather than local adaptation to diet.

PMID- 20059473
TI  - Inferring continental ancestry of argentineans from Autosomal, Y-chromosomal and
      mitochondrial DNA.
AB  - We investigated the bio-geographic ancestry of Argentineans, and quantified their
      genetic admixture, analyzing 246 unrelated male individuals from eight provinces
      of three Argentinean regions using ancestry-sensitive DNA markers (ASDM) from
      autosomal, Y and mitochondrial chromosomes. Our results demonstrate that
      European, Native American and African ancestry components were detectable in the
      contemporary Argentineans, the amounts depending on the genetic system applied,
      exhibiting large inter-individual heterogeneity. Argentineans carried a large
      fraction of European genetic heritage in their Y-chromosomal (94.1%) and
      autosomal (78.5%) DNA, but their mitochondrial gene pool is mostly of Native
      American ancestry (53.7%); instead, African heritage was small in all three
      genetic systems (<4%). Population substructure in Argentina considering the eight
      sampled provinces was very small based on autosomal (0.92% of total variation was
      between provincial groups, p = 0.005) and mtDNA (1.77%, p = 0.005) data (none
      with NRY data), and all three genetic systems revealed no substructure when
      clustering the provinces into the three geographic regions to which they belong.
      The complex genetic ancestry picture detected in Argentineans underscores the
      need to apply ASDM from all three genetic systems to infer geographic origins and
      genetic admixture. This applies to all worldwide areas where people with
      different continental ancestry live geographically close together.

PMID- 20059474
TI  - The effect of systematic medication review in elderly patients admitted to an
      acute ward of internal medicine.
AB  - Elderly patients are vulnerable to medication errors and adverse drug events due
      to increased morbidity, polypharmacy and inappropriate interactions. The
      objective of this study was to investigate whether systematic medication review
      and counselling performed by a clinical pharmacist and clinical pharmacologist
      would reduce length of in-hospital stay in elderly patients admitted to an acute
      ward of internal medicine. A randomized, controlled study of 100 patients aged 70
      years or older was conducted in an acute ward of internal medicine in Denmark.
      Intervention arm: a clinical pharmacist conducted systematic medication reviews
      after an experienced medical physician had prescribed the patients' medication.
      Information was collected from medical charts, interview with the patients and
      database registrations of drug purchase. Subsequently, medication histories were
      conferred with a clinical pharmacologist and advisory notes recommending
      medication changes were completed. Physicians were not obliged to comply with the
      recommendations. Control arm: medication was reviewed by usual routine in the
      ward. Primary end-point was length of in-hospital stay. In addition,
      readmissions, mortality, contact to primary healthcare and quality of life were
      measured at 3-month follow-up. In the intervention arm, the mean length of in
      hospital stay was 239.9 hr (95% CI: 190.2-289.6) and in the control arm: 238.6 hr
      (95% CI: 137.6-339.6), which was neither a statistical significant nor a
      clinically relevant difference. Moreover, no differences were observed for any of
      the secondary end-points. Systematic medication review and medication counselling
      did not show any effect on in-hospital length of stay in elderly patients when
      admitted to an acute ward of internal medicine.

PMID- 20059475
TI  - Pattern recognition receptors of innate immunity and their application to tumor
      immunotherapy.
AB  - Dendritic cells (DC) begin maturation in response to complex stimuli consisting
      of antigens and pattern molecules (PAMP) for the activation of the immune system.
      Immune adjuvant usually contains PAMP. Infection represents one event that is
      capable of inducing such a complex set of stimuli. Recently, DC were subdivided
      into a number of subsets with distinct cell-surface markers, with each subset
      displaying unique differential maturation in response to pattern molecules to
      induce various types of effector cells. In the present study, we review how
      pattern recognition molecules and adaptors in each DC subset drive immune
      effector cells and their effect in the stimulated DC. Although tumor cells harbor
      tumor-associated antigens, they usually lack PAMP. Hence, we outline the
      properties of exogenously-added PAMP in the modulation of raising tumor immunity.
      In addition, we describe the mechanism by which DC-dependent natural killer
      activation is triggered for the induction of antitumor immunity.

PMID- 20059476
TI  - Cyclin-dependent kinase inhibitor SU9516 enhances sensitivity to methotrexate in
      human T-cell leukemia Jurkat cells.
AB  - Methotrexate (MTX) has been used to treat various hematological malignancies.
      Since MTX prevents tumor cells from proliferating by inhibiting dihydrofolate
      reductase (DHFR), DHFR expression is a key determinant of resistance to MTX in
      malignant hematological tumor cells. The antiproliferative effect of MTX was
      significantly enhanced by the knockdown of DHFR expression by siRNA in Jurkat
      cells. Therefore, a novel strategy down-regulating DHFR expression seems
      promising for enhancing sensitivity to MTX. We found that SU9516, a cyclin
      dependent kinase inhibitor, reduced the expression of both DHFR mRNA and protein.
      Moreover, we found that DHFR promoter activity was attenuated by SU9516 dependent
      on the E2F site. Finally, pretreatment with SU9516 significantly enhanced
      sensitivity to MTX in a colony formation assay. We conclude that a combination of
      cyclin-dependent kinase inhibitors and MTX may be useful for overcoming
      resistance to MTX.

PMID- 20059477
TI  - hTERT-promoter-dependent oncolytic adenovirus enhances the transduction and
      therapeutic efficacy of replication-defective adenovirus vectors in pancreatic
      cancer cells.
AB  - Adenovirus-mediated gene therapy shows promise for cancer therapy, but transgene
      expression of replication-defective adenovirus may be low and transient in
      clinical settings. Recent reports have shown that the use of a conditionally
      replication-competent adenovirus (CRAd) enhanced the gene transduction of a
      replication-defective adenovirus vector. The control of tumor-stromal
      interactions has also been determined to be important in cancer therapy. In this
      study, we investigated the effect of the human telomerase reverse transcriptase
      (hTERT)-CRAd, Ad5/3hTERTE1, which possesses the tumor-specific hTERT promoter
      with the chimeric fiber 5/3, on the transgene expression and therapeutic efficacy
      of a replication-defective adenovirus vector expressing NK4 under the control of
      the CMV promoter, Ad-NK4. In addition, we established a new strategy to target
      both cancer cells and cancer-stromal interactions. Human pancreatic cancer cells
      were infected with Ad-NK4 and either Ad5/3hTERTE1 (CRAd-combination group) or
      Ad5/3hTERTLuc (control-combination group). In the CRAd-combination group, Ad-NK4
      delivered transgene expression was increased, leading to an enhanced inhibitory
      effect on the invasion of cancer cells. In in vivo experiments, NK4 expression
      within tumors and its inhibitory effect on tumor growth, angiogenesis, and
      metastasis were enhanced in the CRAd-combination group. These results suggest
      that hTERT-CRAd enhances the transgene expression and therapeutic efficacies of
      Ad-NK4, possibly through the in-trans replication of Ad-NK4 induced by adenovirus
      E1 derived from co-infected hTERT-CRAd. This approach may be a promising
      combination therapy against advanced pancreatic cancer.

PMID- 20059478
TI  - High-density lipoprotein affects antigen presentation by interfering with lipid
      raft: a promising anti-atherogenic strategy.
AB  - Atherosclerosis is a chronic inflammatory disease. Immunomodulation of
      atherosclerosis emerges as a promising approach to prevention and treatment of
      this widely prevalent disease. The function of high-density lipoprotein (HDL) to
      promote reverse cholesterol transport may explain the ability of its protection
      against atherosclerosis. Findings that HDL and apolipoprotein A-I (apoA-I)
      inhibited the ability of antigen presenting cells (APCs) to stimulate T cells
      might be attributed to lipid raft, a cholesterol-rich microdomain exhibiting
      functional properties depending largely upon its lipid composition. Thus,
      modulating cholesterol in lipid raft may provide a promising anti-atherogenic
      strategy.

PMID- 20059479
TI  - Caffeic acid phenethyl ester inhibits nuclear factor-kappaB and protein kinase B
      signalling pathways and induces caspase-3 expression in primary human CD4+ T
      cells.
AB  - Caffeic acid phenethyl ester (CAPE), an active component in propolis, is known to
      have anti-tumour, anti-inflammatory and anti-oxidant properties. In this study,
      the effects of CAPE on the functions of primary human CD4+ T cells were evaluated
      in vitro. CAPE significantly suppressed interferon (IFN)-gamma and interleukin
      (IL)-5 production and proliferation of CD4+ T cells stimulated by soluble anti
      CD3 and anti-CD28 monoclonal antibodies in both healthy subjects and asthmatic
      patients. CAPE inhibited nuclear factor (NF)-kappaB activation and protein kinase
      B (Akt) phosphorylation, but not p38 mitogen-activated protein kinase (MAPK)
      phosphorylation in T cells. CAPE also induced active caspase-3 expression in CD4+
      T cells; CCR4+CD4+ T cells were more sensitive to CAPE induction than CXCR3+CD4+
      T cells. Together, these results indicate that CAPE inhibits cytokine production
      and proliferation of T cells, which might be related to the NF-kappaB and Akt
      signalling pathways, and that CCR4+CD4+ T cells are more sensitive to CAPE
      inhibition. This study provides a new insight into the mechanisms of CAPE for
      immune regulation and a rationale for the use of propolis for the treatment of
      allergic disorders.

PMID- 20059480
TI  - Epitope shift of proteinase-3 anti-neutrophil cytoplasmic antibodies in patients
      with small vessel vasculitis.
AB  - Anti-neutrophil cytoplasmic antibodies against proteinase 3 (PR3-ANCA) are used
      as diagnostic tools for patients with small vessel vasculitis (AASV). We have
      produced chimeric mouse/human PR3 molecules and investigate changes in reactivity
      over time and the possible relationship between epitope specificity and clinical
      course. Thirty-eight PR3-ANCA-positive patients diagnosed between 1990 and 2003
      were followed until December 2005. Plasma was collected at each out-patient visit
      and older samples were retrieved retrospectively. Patients reacted with multiple
      epitopes at the time of diagnosis. At subsequent relapses 12 patients shifted
      reactivity, in 11 cases from epitopes located in the C-terminal towards epitopes
      in the N-terminal. Patients with reactivity against N-terminal parts of PR3 at
      diagnosis had a significantly lower relapse rate, 30% compared to 78% in the
      group with predominantly C-terminal reactivity (P = 0.04). The reactivity pattern
      did not correlate to outcome measured as death, end-stage renal disease or
      vasculitis activity index score (VDI) at 5 years. Further research is necessary
      to conclude if this is a general phenomenon.

PMID- 20059481
TI  - Islet inflammation and CXCL10 in recent-onset type 1 diabetes.
AB  - Type 1 diabetes results from a T cell-mediated destruction of insulin-producing
      pancreatic beta cells. Little is known on local factors contributing to migration
      of T cells to pancreatic tissue. We recently demonstrated evidence of viral
      infection in beta cells in several recent-onset type 1 diabetes patients. Islet
      inflammation was analysed in a series of new- or recent-onset type 1 diabetic
      patients and non-diabetic control subjects. Autoimmune T cell reactivity was
      studied in lymphocytes derived from pancreas-draining lymph nodes of one recent
      onset type 1 diabetes patient in partial clinical remission. Insulitic lesions
      were characterized by presence of beta cells, elevated levels of the chemokine
      CXCL10 and infiltration of lymphocytes expressing the corresponding chemokine
      receptor CXCR3 in all pancreatic lesions of type 1 diabetes patients, regardless
      of enterovirus infection of beta cells. CXCR3 and CXCL10 were undetectable in
      pancreata of non-diabetic control subjects. T cells isolated from draining lymph
      nodes of a recent-onset patient with virally infected beta cells and in clinical
      remission reacted with multiple islet autoantigens and displayed a mixed
      interferon (IFN)-gamma/interleukin (IL)-10 cytokine pattern. Our data point to
      CXCL10 as an important cytokine in distressed islets that may contribute to
      inflammation leading to insulitis and beta cell destruction, regardless of local
      viral infection. We demonstrate further pro- and anti-inflammatory islet
      autoreactivity, indicating that different adaptive and innate immune responses
      may contribute to insulitis and beta cell destruction.

PMID- 20059483
TI  - Risk-reducing mastectomy and salpingo-oophorectomy in unaffected BRCA mutation
      carriers: uptake and timing.
AB  - Once female carriers of a BRCA mutation are identified they have to make
      decisions on risk management. The aim of this study is to outline the uptake of
      risk-reducing surgery in the Danish population of BRCA mutation positive women
      and to search for factors affecting this decision. We analysed data from 306
      healthy BRCA carriers with no personal history of ovarian or breast cancer. We
      found a 10-year uptake of 75% for risk-reducing salpingo-oophorectomy and 50% for
      risk-reducing mastectomy by time to event analysis. Age and childbirth influenced
      this decision. The uptake rate has not changed significantly over the last
      decade. Risk-reducing surgeries are widely acceptable among Danish BRCA mutation
      positive women and the uptake of prophylactic mastectomy is higher than in most
      other countries.

PMID- 20059482
TI  - Sequential expression of macrophage anti-microbial/inflammatory and wound healing
      markers following innate, alternative and classical activation.
AB  - The present study examines the temporal dynamics of macrophage activation marker
      expression in response to variations in stimulation. We demonstrate that markers
      can be categorized as 'early' (expressed most abundantly at 6 h post-stimulation)
      or 'late' (expressed at 24 h post-stimulation). Thus nos2 and p40 (IL-12/IL-23)
      are early markers of innate and classical activation, while dectin-1 and mrc-1
      are early markers and fizz1 (found in inflammatory zone-1) and ym1 are late
      markers of alternative activation. Furthermore, argI is a late marker of both
      innate and alternative activation. The ability of interferon (IFN)-gamma to alter
      these activation markers was studied at both the protein level and gene level. As
      reported previously, IFN-gamma was able to drive macrophages towards the
      classical phenotype by enhancing nos2 gene expression and enzyme activity and p40
      (IL-12/IL-23) gene expression in lipopolysaccharide (LPS)-stimulated macrophages.
      IFN-gamma antagonized alternative macrophage activation, as evident by reduced
      expression of dectin-1, mrc-1, fizz1 and ym1 mRNA transcripts. In addition, IFN
      gamma antagonized arginase activity irrespective of whether macrophages were
      activated innately or alternatively. Our data explain some apparent
      contradictions in the literature, demonstrate temporal plasticity in macrophage
      activation states and define for the first time 'early' and 'late' markers
      associated with anti-microbial/inflammatory and wound healing responses,
      respectively.

PMID- 20059484
TI  - Co-occurring diagnoses among FMR1 premutation allele carriers.
AB  - Following the discovery of two disorders associated with premutation alleles of
      the fragile X mental retardation gene (FMR1), primary ovarian insufficiency
      [fragile X-associated primary ovarian insufficiency (FXPOI)] and a tremor/ataxia
      syndrome [fragile X-associated tremor/ataxia disorder (FXTAS)], numerous studies
      have examined other potential co-morbid conditions, including neuropsychological
      deficits. Here, the frequency of self-reported diagnoses obtained through medical
      history interviews from FMR1 premutation carriers and non-carriers aged 18-50
      were analyzed. Study subjects included 537 women, 334 of whom carry the
      premutation and 151 men, 37 of whom carry the premutation. Men with the
      premutation did not report any medical conditions at higher rates compared with
      non-carriers, controlling for age, ethnicity/race, and household income. Women
      with the premutation reported mental health disorders [i.e. attention deficit
      hyperactivity disorder (ADHD), anxiety, depression] significantly more often than
      non-carriers. However, after adjusting for covariates, these increased rates were
      not statistically significant. Additional follow-up analyses examined the
      consequence of ovarian dysfunction as a cause of co-occurring conditions. Women
      with an indication of ovarian insufficiency (i.e. irregular cycles) reported
      higher rates of thyroid problems and depression/anxiety. Because only women, not
      men, reported these conditions more often, the relationship between FXPOI and
      hormone irregularities in women should be explored for a potential link with the
      increase in the reported medical conditions.

PMID- 20059485
TI  - Do common in silico tools predict the clinical consequences of amino-acid
      substitutions in the CFTR gene?
AB  - Computational methods are used to predict the molecular consequences of amino
      acid substitutions on the basis of evolutionary conservation or protein
      structure, but their utility in clinical diagnosis or prediction of disease
      outcome has not been well validated. We evaluated three popular computer
      programs, namely, PANTHER, SIFT and PolyPhen, by comparing the predicted clinical
      outcomes for a group of known CFTR missense mutations against the diagnosis of
      cystic fibrosis (CF) and clinical manifestations in cohorts of subjects with CF
      disease and CFTR-related disorders carrying these mutations. Owing to poor
      specificity, none of tools reliably distinguished between individual mutations
      that confer CF disease from mutations found in subjects with a CFTR-related
      disorder or no disease. Prediction scores for CFTR mutations derived from PANTHER
      showed a significant overall statistical correlation with the spectrum of disease
      severity associated with mutations in the CFTR gene. In contrast, PolyPhen- and
      SIFT-derived scores only showed significant differences between CF-causing and
      non-CF variants. Current computational methods are not recommended for
      establishing or excluding a CF diagnosis, notably as a newborn screening strategy
      or in patients with equivocal test results.

PMID- 20059486
TI  - Phenotypic variability, neurological outcome and genetics background of 6
      pyruvoyl-tetrahydropterin synthase deficiency.
AB  - This study aimed to investigate the clinical variability and factors implied in
      the outcome of 6-pyruvoyl-tetrahydropterin synthase deficiency (PTPSd).
      Biochemical and clinical phenotype, treatment variables, and 6-pyruvoyl
      tetrahydropterin synthase (PTS) genotype, were explored retrospectively in 19
      Italian patients (12 males and 7 females, aged 4 months to 33 years). According
      to the level of biogenic amines in cerebrospinal fluid (CSF) at the diagnosis,
      the patients were classified as mild (6) (normal level) or severe (13) (abnormal
      low level) form (MF and SF, respectively). Blood Phe ranged from 151 to 1053
      micromol/l in MF (mean +/- SD: 698 +/- 403) and 342-2120 micromol/l in SF (mean
      +/- SD: 1175 +/- 517) (p = 0.063). Patients with MF showed a normal neurological
      development (a transient dystonia was detected in one), while all SF patients
      except one presented with severe neurological impairment and only four had a
      normal neurological development. The outcome of the SF was influenced by the
      precocity of the treatment. Serial CSF examinations revealed a decline of 5
      hydroxyindolacetic acid in MFs and an incomplete restoration of neurotransmitters
      in SFs: neither obviously affected the prognosis. PTS gene analysis detected 17
      different mutations (seven so far unreported) (only one affected allele was
      identified in three subjects). A good correlation was found between genotype and
      clinical and biochemical phenotype. The occurrence of brain neurotransmitter
      deficiency and its early correction (by the therapy) are the main prognostic
      factors in PTPSd.

PMID- 20059487
TI  - The management of splenic artery aneurysm in patients awaiting liver
      transplantation.
AB  - Splenic artery aneurysms (SAAs) are the third most common forms of intra
      abdominal aneurysm, and the most commonly encountered visceral aneurysms in the
      general population. SAAs occur more commonly in patients with portal hypertension
      and liver failure and, as such, are often encountered in patients undergoing high
      resolution abdominal imaging as part of a work-up for liver transplantation.
      While rupture rates of between 2% and 10% have been reported in the literature,
      little is known about the natural history and behavior of these lesions in
      patients with liver disease. Interventional management options pose a challenge
      given the high anesthetic and surgical risk of such patients. This study was
      conducted to study the management of all SAAs diagnosed among patients presenting
      for a liver transplant assessment at a single center over a three-yr period. We
      discuss the presentation and management options, with elective and emergent
      presentation of SAA in patients with end-stage liver disease.

PMID- 20059488
TI  - Dental caries risk indicators among Australian Aboriginal young adults.
AB  - OBJECTIVES: To determine dental caries risk indicators among a birth cohort of
      Australian Aboriginal young adults (n=442). METHODS: Data were from the
      Aboriginal Birth Cohort study, a prospective longitudinal investigation of
      Aboriginal individuals born 1987-1990 at an Australian regional hospital. Models
      representing demographic, socioeconomic, behavioural, dental service utilization
      and clinical oral health variables were tested using multivariate regression.
      RESULTS: The percent DT>0 was 72.9 (95% CI 68.7-77.1), mean DT was 4.19 (95% CI
      3.8-4.6), percent DMFT>0 was 77.4 (95% CI 73.5-81.3) and mean DMFT was 4.84 (95%
      CI 4.4-5.3). After controlling for other covariates, risk indicators for percent
      DT>0 included soft drink consumption every day or a few times a week (PR 1.25,
      95% CI 1.08-1.45), not consuming milk every day or a few times a week (PR 1.16,
      95% CI 1.04-1.30) and sweet consumption every day or a few times a week (PR 1.18,
      95% CI 1.04-1.33). Risk indicators for mean DT included sweet consumption every
      day or a few times a week (B=1.14, 95% CI 0.27-2.02), nonownership of a
      toothbrush (B=0.91, 95% CI 0.10-1.87) and presence of plaque (B=2.46, 95% CI 0.96
      3.96). Those with 4 +  occupants in their house the previous night had 1.2 times
      the prevalence of having DMFT>0 than their counterparts with less household
      occupants (95% CI 1.01-1.49). Percent DMFT>0 was also associated with consumption
      of soft drink every day or a few times a week (PR 1.18, 95% CI 1.04-1.34) and
      consumption of sweets every day or a few times a week (PR 1.23, 95% CI 1.10
      1.37). Mean DMFT was higher among those who consumed sweets every day or a few
      times a week (B = 0.13, 95% CI 0.05-0.22) and who had dental anxiety (B=0.10, 95%
      CI 0.01-0.19). CONCLUSIONS: In an Australian Aboriginal young adult cohort, risk
      indicators for dental caries included social determinants such as household size,
      dietary behaviours such as regular consumption of soft drink and sweets, dental
      behaviour such as nonownership of a toothbrush and dental anxiety.

PMID- 20059489
TI  - Good Work for dentists - a qualitative analysis.
AB  - OBJECTIVE: This study explores dentists' perceptions of Good Work in the meaning
      of positive and rewarding aspects in their work in contrast to a traditional
      problem-centred focus on work life. METHODS: Nine informants were selected among
      Danish and Swedish general dental practitioners to obtain variation as to country
      of origin, gender, age and clinical work experience. Semi-structured, in-depth
      interviews were audio-recorded and transcribed verbatim in the original language.
      Statements concerning positive aspects of work were used for systematic text
      condensation according to the principles of Giorgi's phenomenological analysis,
      as modified by Malterud, generalizing descriptions reflecting aspects of Good
      Work. Selection of participants continued until saturation of the emerging
      categories was achieved. RESULTS: The core of Good Work emanates from the
      clinical encounter: from the relation with the patient and from the opportunity
      to carry out high quality odontological handicraft. Social relations at the
      workplace, as well as organizational values and conditions were perceived as
      influencing the opportunities to achieve the rewarding aspects from the clinical
      encounter. CONCLUSIONS: The results implicate a need for developing a work
      environmental model with intrinsic as well as extrinsic rewards when dealing with
      human service organizations. At policy level it is necessary to address the
      professional culture.

PMID- 20059490
TI  - Association between use of asthma drugs and prevalence of demarcated opacities in
      permanent first molars in 6-to-8-year-old Danish children.
AB  - OBJECTIVES: Demarcated opacities in permanent first molars are common
      developmental tooth defects, characterized by areas with insufficient
      mineralization of the enamel. The defects present clinically as a continuum from
      creamy-white demarcated opacities, yellowish-brown demarcated opacities to
      macroscopic loss of tooth substance. The etiology is sparsely elucidated, but
      asthma drugs have been suspected to increase the prevalence. The aim of this
      study was to examine the prevalence of demarcated opacities in permanent first
      molars among 6-to-8-year-old children with prescriptions and without
      prescriptions for asthma drugs. METHODS: In a cross-sectional study in two Danish
      municipalities, all children aged 6-8 years (n = 891) were included. A total of
      745 (83.6%) went through a dental examination during which demarcated opacities
      and tooth substance loss due to these were recorded. The analyses were restricted
      to 647 children in whom all four permanent first molars had erupted. Data on use
      of asthma drugs from birth until the time of the dental examination were obtained
      from a population-based pharmaco-epidemiological prescription database. RESULTS:
      Among 47 children with prescriptions for both inhaled beta(2)-agonists and
      inhaled corticosteroids before the age of 3 years, 15 (31.9%) had demarcated
      opacities of any type, and six children (12.8%) had opacity-related loss of tooth
      substance. Among 264 children with no prescriptions for either inhaled or oral
      asthma drugs from birth until the date of the dental examination, 96 (36.4%) had
      demarcated opacities of any type, and 13 (4.9%) had opacity-related loss of tooth
      substance. The odds ratio (OR) of any demarcated opacity, and of opacity-related
      loss of tooth substance in children with prescriptions for both inhaled beta(2)
      agonists and inhaled corticosteroids before the age of 3 years was 0.82 (95% CI:
      0.39-1.65), and 2.42 (95% CI: 0.70-7.43). CONCLUSIONS: Children with
      prescriptions for inhaled asthma drugs before the age of 3 years did not have an
      overall increased risk of demarcated opacities in first permanent molar but they
      seemed to have an increased risk of the severe demarcated opacities, i.e.
      opacities resulting in macroscopic loss of tooth substance, and possibly a need
      for restorative care.

PMID- 20059491
TI  - Fragrance contact allergic patients: strategies for use of cosmetic products and
      perceived impact on life situation.
AB  - BACKGROUND: Fragrance ingredients are a common cause of contact allergy. Very
      little is known about these patients' strategies to manage their disease and the
      effect on their daily lives. OBJECTIVES: To investigate if patients with
      diagnosed fragrance contact allergy used scented products, how they identified
      tolerated products, and if fragrance allergy affected their daily living. METHOD:
      One hundred and forty-seven patients diagnosed with fragrance contact allergy in
      a 20-month period were included and received a postal questionnaire concerning
      the subjects of the study. One hundred and seventeen (79.6%) replied. RESULTS: In
      total, 53/117 (45.3%) responded that they had found some scented products that
      they could tolerate. Thirty-seven (31.6%) had not tried to find any scented
      products and 26 (22%) had tried but could not find any. The methods most often
      used were trying different products and reading the ingredient label. Of the
      total respondents, 17.1% reported sick-leave due to fragrance allergy and 45.3%
      found that fragrance allergy significantly affected their daily living.
      CONCLUSION: Many patients with fragrance contact allergy succeeded in finding
      some scented products, which they could tolerate, e.g. by use of ingredient
      labelling, but a significant proportion had continued skin problems. Almost half
      of the patients perceived that fragrance allergy significantly affected their
      daily lives.

PMID- 20059492
TI  - Ethnic variations in facial skin neurosensitivity assessed by capsaicin detection
      thresholds.
AB  - BACKGROUND: Ethnic variations in sensitive skin have not been thoroughly explored
      and remain controversial. OBJECTIVE: To objectively assess ethnic variations in
      facial skin neurosensitivity through individual detection thresholds of topically
      applied capsaicin. PATIENTS/METHODS: The single-blind, controlled study was
      performed in 144 women from three ethnicities: Asian, African, and Caucasian.
      Five solutions with increasing capsaicin concentration were successively applied
      to one side of nasolabial folds, while the other side simultaneously received the
      vehicle as control. The test was discontinued when the volunteer reported on the
      capsaicin side a sensation whatever its nature. Otherwise the experimenter
      continued the test, using the next solution with higher capsaicin content and so
      on, until the subject experienced a sensation on the capsaicin side. RESULTS:
      Each ethnic group was divided into six sub-groups according to the level of
      sensitivity to capsaicin, i.e. from detection of the lowest concentration up to
      no detection of the highest concentration, 100-fold higher. Asian women tended to
      have higher capsaicin detection thresholds than Caucasians, but lower thresholds
      than Africans. Nevertheless, the distribution did not greatly differ between the
      three ethnicities. CONCLUSIONS: The capsaicin skin neurosensitivity test is
      painless and the changes across individuals of different ethnic backgrounds
      appear minimal.

PMID- 20059493
TI  - Does the extreme skin sensitization potency of benzoquinone result from special
      chemistry?
AB  - BACKGROUND: Benzoquinone is known to be an extreme skin sensitizer. Until now
      there has been no consideration of whether it owes its extreme skin sensitization
      potency to unique aspects of its chemistry or simply to its high reactivity as a
      Michael acceptor. OBJECTIVES: To answer these questions, we have applied two
      mechanistic approaches to estimate a theoretical potency value for benzoquinone.
      PATIENTS/METHODS: A mechanistic read-across (MRA) approach, using known potency
      data for moderate sensitizers in the Michael acceptor domain, and a published
      quantitative mechanistic model (QMM) for skin sensitization potency of Michael
      acceptors, all in the moderate and weak range, were used. RESULTS: The read
      across approach gives a theoretical local lymph node assay (LLNA) EC3 value of
      0.04%, and the QMM approach gives a theoretical value of 0.013%, compared with an
      experimental value of 0.010%. CONCLUSIONS: The good agreement between the
      theoretical and experimental EC3 values supports the strength of the MRA and QMM
      approaches, and provides strong evidence that the extreme sensitization potency
      of benzoquinone can be attributed solely to its high reactivity as a Michael
      acceptor.

PMID- 20059494
TI  - Contact allergens and irritants in household washing and cleaning products.
AB  - BACKGROUND: Household cleaning products often contain potential allergens and
      irritants but allergic contact dermatitis from these products in general
      consumers is rarely reported in the literature. OBJECTIVES: The purpose of this
      study was to evaluate the presence of irritants and allergens as indicated on the
      labels or on the product information found on the website of household cleaning
      products marketed in Italy. MATERIAL/METHODS: We examined the labels and the
      product information of 291 liquid household washing and cleaning products,
      including 43 washing-up liquids, 63 laundry detergents, 61 fabric conditioners,
      47 spray detergents, and 77 hard surface cleaning products. We obtained the data
      from the product information found on the websites for 263 products and directly
      on the product packages for 28 products. For each product we specifically
      recorded the presence of surfactants, preservatives, and fragrances listed in
      Annex III of Directive 76/768/EEC. RESULTS: The websites of two Italian brands do
      not respect EU regulations as they provide product information only with bar
      codes of the products. Preservatives and fragrances are the main allergens
      declared in the label of household cleaning products with
      methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) listed in 35.7% and
      limonene in 43.6% of the products. Surfactants were listed in 16.5% of the
      studied products. CONCLUSIONS: Our study shows that household cleaning products
      in Italian market contain several allergens, particularly preservatives and
      fragrances. For consumers, at least in Italy, it may not be easy to retrieve
      product information from the website for two widely sold brands. The information
      had to be taken from the actual package.

PMID- 20059495
TI  - Allergic contact dermatitis from decyl glucoside in an antiseptic lotion.

PMID- 20059496
TI  - Occupational contact dermatitis caused by probenazole in agricultural chemical
      factories.

PMID- 20059497
TI  - An unusual case of contact dermatitis caused by wooden bracelets.

PMID- 20059498
TI  - Contact allergy from alkyl rhamnoside-C5.

PMID- 20059499
TI  - Maculopapular exanthem from propolis: case report and review of systemic
      cutaneous and non-cutaneous reactions.

PMID- 20059500
TI  - Systemic allergic dermatitis caused by the solvent of Eligard.

PMID- 20059501
TI  - Type I ammonium persulfate allergy with no cross reactivity to potassium
      persulfate.

PMID- 20059502
TI  - Allergic contact dermatitis from tincture of benzoin with multiple concomitant
      reactions.

PMID- 20059503
TI  - Contact allergy to trimethyl-benzenepropanol (Majantol).

PMID- 20059504
TI  - Hand eczema in Copenhagen hairdressers--prevalence and under-reporting to
      occupational registers.

PMID- 20059506
TI  - Hurthle cell carcinoma with myxoid stroma - a rare entity and a diagnosis
      pitfall.

PMID- 20059507
TI  - Assisted reproductive technologies and risk of cerebral palsy among singletons in
      Australia.

PMID- 20059508
TI  - Enabling self-directed computer use for individuals with cerebral palsy: a
      systematic review of assistive devices and technologies.
AB  - AIM: The purpose of this study was to systematically review published evidence on
      the development, use, and effectiveness of devices and technologies that enable
      or enhance self-directed computer access by individuals with cerebral palsy (CP).
      METHODS: Nine electronic databases were searched using keywords 'computer',
      'software', 'spastic', 'athetoid', and 'cerebral palsy'; the reference lists of
      articles thus identified were also searched. Thirty articles were selected for
      review, with 23 reports of development and usability testing of devices and seven
      evaluations of algorithms to increase computer recognition of input and cursor
      movements. RESULTS: Twenty-four studies had fewer than 10 participants with CP,
      with a wide age range of 5 to 77 years. Computer task performance was usually
      tested, but only three groups sought participant feedback on ease and comfort of
      use. International standards exist to evaluate effectiveness of non-keyboard
      devices, but only one group undertook this testing. None of the study designs
      were higher than American Academy for Cerebral Palsy and Developmental Medicine
      level IV. INTERPRETATION: Access solutions for individuals with CP are in the
      early stages of development. Future work should include assessment of end-user
      comfort, effort, and performance as well as design features. Engaging users and
      therapists when designing and evaluating technologies to enhance computer access
      may increase acceptance and improve performance.

PMID- 20059509
TI  - Evidence-based life expectancy.

PMID- 20059510
TI  - Assessing bimanual performance in young children with hemiplegic cerebral palsy:
      a systematic review.
AB  - AIM: This systematic review investigated the availability of assessment tools to
      evaluate bimanual skills in young children (< or = 3y) with hemiplegic cerebral
      palsy. Evidence for validity, reliability, and clinical utility of the identified
      instruments was sought. METHOD: Ten electronic databases and grey literature were
      searched (earliest 1806) to February 2009 to identify articles that met criteria
      related to the child's age and diagnosis, and included a discrete bimanual
      assessment. Further searches for evidence of psychometric properties of each
      identified assessment were undertaken. For quality criteria, we evaluated the
      internal validity of each study and appraised the validity and reliability of
      identified assessments. RESULTS: From 1435 papers retrieved, 15 were eligible for
      inclusion, and 11 assessments of bimanual performance were identified. Ten
      assessments had inadequate evidence for reliability and validity. Only the
      Assisting Hand Assessment had evidence for reliability and validity for its
      intended purposes. INTERPRETATION: Reliability and validity are fundamental
      considerations when developing or selecting assessments. Additional
      considerations for assessing young children include the following: (1)
      standardized administration and scoring; (2) items that capture the complexity of
      bimanual behaviour; and (3) protocols and items targeted within a small age range
      to meet specific developmental needs. A validated assessment of younger infants
      is needed to support early intervention during this period of rapid brain
      development.

PMID- 20059511
TI  - Predictive validity of attentional functions in differentiating children with and
      without ADHD: a componential analysis.
AB  - AIM: The objective of this study was to investigate which attentional components
      are of predictive utility in differentiating children with attention-deficit
      hyperactivity disorder, combined type (ADHD-C) from their peers without ADHD.
      METHODS: Thirty-four children participated in the study: 17 males with ADHD-C
      (mean age 10y 4mo, SD 1y 9mo) and 17 comparison children (12 males, 5 females;
      mean age 10y 8mo, SD 1.7y). Attentional functions were assessed using a computer
      administered, child-friendly test series in German (i.e. Testbatterie zur
      Aufmerksamkeitsprufung fur Kinder; KITAP). The KITAP measures several attentional
      components, including alertness and executive attention (inhibition, divided
      attention, flexibility). RESULTS: The variable best able to discriminate between
      children with and without ADHD-C was found to be response time variability in a
      go/no go task, followed by, in order, number of errors in a divided attention
      task and response time variability in an alertness task. However, group
      discrimination was not facilitated by differences in either response latency or
      accuracy of response in visuospatial attention and attentional flexibility tasks.
      INTERPRETATION: The assessment of attentional functions proved to be a powerful
      instrument for discriminating between children with and without ADHD-C. Notably,
      the discriminative power of executive attention was found to be task dependent
      and dependent on processing demands.

PMID- 20059512
TI  - The value of the clinical examination revisited.

PMID- 20059513
TI  - Lesions in early cerebellar development--do they matter?

PMID- 20059515
TI  - Anti-N-Methyl-D-aspartate receptor encephalitis: a new entity?

PMID- 20059514
TI  - Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY,
      or XXY: a systematic review.
AB  - AIM: To review systematically the neurodevelopmental characteristics of
      individuals with sex chromosome trisomies (SCTs). METHOD: A bibliographic search
      identified English-language articles on SCTs. The focus was on studies unbiased
      by clinical referral, with power of at least 0.69 to detect an effect size of
      1.0. RESULTS: We identified 35 articles on five neonatally identified samples
      that had adequate power for our review. An additional 11 studies were included
      where cases had been identified for reasons other than neurodevelopmental
      concerns. Individuals with an additional X chromosome had mean IQs that were
      within broadly normal limits but lower than the respective comparison groups,
      with verbal IQ most affected. Cognitive outcomes were poorest for females with
      XXX. Males with XYY had normal-range IQs, but all three SCT groups (XXX, XXY, and
      XYY) had marked difficulties in speech and language, motor skills, and
      educational achievement. Nevertheless, most adults with SCTs lived independently.
      Less evidence was available for brain structure and for attention, social, and
      psychiatric outcomes. Within each group there was much variation. INTERPRETATION:
      Individuals with SCTs are at risk of cognitive and behavioural difficulties.
      However, the evidence base is slender, and further research is needed to
      ascertain the nature, severity, and causes of these difficulties in unselected
      samples.

PMID- 20059516
TI  - Fetal growth from mid- to late pregnancy: the Generation R Study.

PMID- 20059517
TI  - The role of observation of spontaneous movements at 3 months in infants at risk
      of developing hemiplegia.

PMID- 20059518
TI  - Genetic causes of syndromic and non-syndromic autism.
AB  - AIMS: Over the past decade, genetic tests have become available for numerous
      heritable disorders, especially those whose inheritance follows the Mendelian
      model. Autism spectrum disorders (ASDs) represent a group of developmental
      disorders with a strong genetic basis. During the past few years, genetic
      research in ASDs has been successful in identifying several vulnerability loci
      and a few cytogenetic abnormalities or single-base mutations implicated in the
      causation of autism. METHOD: In this study the literature was reviewed to
      highlight genotype-phenotype correlations between causal gene mutations or
      cytogenetic abnormalities and behavioural or morphological phenotypes. RESULTS:
      Based on this knowledge, practical information is offered to help clinicians
      pursue targeted genetic testing of individuals with autism whose clinical
      phenotype is suggestive of a specific genetic or genomic aetiology.
      INTERPRETATION: Comprehensive research into the molecular mechanism of autism is
      required to aid the development of disease-specific targeted therapies. In order
      to transfer this recently acquired knowledge into clinical practice, it is
      critical to define a set of phenotypic inclusion criteria that must be met by
      affected probands to justify their enrolment in a specific genetic testing
      programme.

PMID- 20059519
TI  - Obstetric brachial plexus palsy.

PMID- 20059520
TI  - Congenital malformations and the cerebral palsies - deja vu, but now what?

PMID- 20059521
TI  - Apolipoprotein E genotype and cerebral palsy.

PMID- 20059522
TI  - Examining speech of very-low-birthweight children during everyday activities.

PMID- 20059523
TI  - Communication activity and participation research.

PMID- 20059524
TI  - Sperm of colourful males are better protected against oxidative stress.
AB  - Sperm cells are highly vulnerable to free radicals, and sperm quality and male
      fertility are critically affected by oxidative stress. Recently, sexual
      ornaments, particularly carotenoid-based colourful traits, have been proposed to
      depend on a male's capacity to resist oxidative stress, and thus to signal sperm
      quality. We conducted an experimental test of this hypothesis on great tits Parus
      major, in which adults are sexually dichromatic in carotenoid-based breast
      plumage. We report the first evidence that ornaments and sperm quality may be
      linked through oxidative stress. When experimentally subjected to oxidative
      stress resulting from increased workload, less colourful males suffered a greater
      reduction in sperm motility and swimming ability, and increased levels of sperm
      lipid peroxidation compared to more colourful males. Moreover, the level of sperm
      lipid peroxidation was negatively correlated with sperm quality. Finally,
      carotenoid supplementation increased sperm quality of less colourful males,
      suggesting that pale males are deficient in carotenoid antioxidants.

PMID- 20059525
TI  - The intraspecific scaling of metabolic rate with body mass in fishes depends on
      lifestyle and temperature.
AB  - Metabolic energy fuels all biological processes, and therefore theories that
      explain the scaling of metabolic rate with body mass potentially have great
      predictive power in ecology. A new model, that could improve this predictive
      power, postulates that the metabolic scaling exponent (b) varies between 2/3 and
      1, and is inversely related to the elevation of the intraspecific scaling
      relationship (metabolic level, L), which in turn varies systematically among
      species in response to various ecological factors. We test these predictions by
      examining the effects of lifestyle, swimming mode and temperature on
      intraspecific scaling of resting metabolic rate among 89 species of teleost fish.
      As predicted, b decreased as L increased with temperature, and with shifts in
      lifestyle from bathyal and benthic to benthopelagic to pelagic. This effect of
      lifestyle on b may be related to varying amounts of energetically expensive
      tissues associated with different capacities for swimming during predator-prey
      interactions.

PMID- 20059526
TI  - Interictal dysphoric disorder and periictal dysphoric symptoms in patients with
      epilepsy.
AB  - PURPOSE: The issue of phenomenology of mood disorders in epilepsy still remains
      controversial. It has been suggested that a subgroup of patients may develop an
      affective syndrome also known as interictal dysphoric disorder (IDD). However,
      the number of behavioral changes that may occur around the ictus needs to be
      taken into account for an accurate distinction between "true" psychiatric
      phenomenology and periictal phenomena. This study aimed at identifying clinical
      correlates of the IDD, with special attention to the relationship between
      symptoms and seizures. METHODS: A sample of 142 consecutive adult outpatients
      with epilepsy were assessed using the Interictal Dysphoric Disorder Inventory
      (IDDI), a 38-item, self-report questionnaire specifically developed to evaluate
      presence and severity of IDD symptoms as well as their habitual association with
      seizures (coded as before, after, during, or when seizure-free) and their
      duration. RESULTS: IDD was diagnosed in 31 subjects but symptoms showed a clear
      cut relationship with epileptic seizures in 54.8% of cases, leading to an
      operative distinction between true IDD and periictal dysphoric symptoms (PDS).
      There was no significant difference among patients with IDD, PDS, or those
      without psychopathology. In the IDD group, symptoms were chronic and unremitting
      in one-third of cases, with labile affective symptoms being correlated with age
      at onset of seizures (rho = -0.612, p = 0.020) and duration of the epilepsy (rho
      = 0.833, p < 0.001). DISCUSSION: An operative distinction between IDD and PDS
      bears the opportunity to identify different clinical endophenotypes that may have
      different prognoses and require different treatment strategies.

PMID- 20059527
TI  - THP-COP regimen for the treatment of peripheral T-cell lymphoma and adult T-cell
      leukemia/lymphoma: a multicenter phase II study.
AB  - OBJECTIVE: The efficacy of pirarubicin (THP)-COP was previously compared with
      cyclophophamide + doxorubicin + vincristine + prednisolone (CHOP) in elderly
      patients with lymphoma. The subset analysis showed that T-cell lymphoma had a
      significantly better response with THP-COP, whereas no such difference was
      observed in B-cell lymphoma. The aim of this study is to confirm the efficacy of
      THP-COP in the treatment of T-cell lymphoma. METHODS: We underwent a multicenter
      phase II study of THP-COP as a first-line treatment for T-cell lymphoma. The
      overall response rate, survival period, and toxicity were analyzed. RESULTS:
      Fifty-three patients were enrolled in this study. Seventeen patients had
      peripheral T-cell lymphoma (PTCL), including nine of PTCL not otherwise specified
      (PTCL-NOS) and eight of angioimmunoblastic T-cell lymphoma (AITL). Thirty-six
      patients had adult T-cell leukemia/lymphoma (ATLL), including 20 of acute type
      and 16 of lymphoma type. A treatment response was obtained in 35 (66%) patients,
      including 17 (32%) complete responses. Median overall survival (OS) and
      progression-free survival (PFS) times were 14.3 months and 5.2 months,
      respectively. Patients with ATLL showed a tendency to obtain low response rate
      (61% vs. 77%, P = 0.27) and had a significantly inferior OS (13.3 vs. 28.6
      months, P = 0.04) and PFS (4.6 vs. 8.1 months, P = 0.01) in comparison with PTCL.
      Grade 3 to 4 neutropenia, anemia, and thrombocytopenia occurred in 72%, 34%, and
      58% of the patients, respectively. Febrile neutropenia was observed in 51% and
      grade 3 non-hematological toxicities in 2-9% of the patients. CONCLUSION: The
      efficacy of THP-COP is equivalent to that of CHOP for the first-line therapy in T
      cell lymphoma.

PMID- 20059528
TI  - Fatal Trichosporon fungemia in patients with hematologic malignancies.
AB  - OBJECTIVE: Invasive Trichosporon infection has been increasingly recognized in
      patients with hematologic malignancies. Our study aims to clarify the clinical
      characteristics of this disease and factors influencing patient prognosis.
      PATIENTS AND METHODS: We retrospectively analyzed 33 cases of Trichosporon
      fungemia (TF) in patients with hematologic malignancies treated at our
      collaborating five hospitals in Japan between 1992 and 2007. RESULTS: The
      majority of these patients had acute leukemia (82%), neutropenia (85%), and a
      history of intensive chemotherapy (91%). TF occurred as a breakthrough infection
      during antifungal therapy in 30 patients (91%), 18 of whom were receiving
      micafungin. The surveillance cultures of most patients were negative for
      Trichosporon. Only a few patients exhibited elevated levels of 1,3-beta-d-glucan
      before positive blood culture. Twenty-five patients (76%) died of this infection.
      The resolution of infection was associated with neutrophil recovery (P = 0.0001),
      absence of hyperglycemia (P = 0.023), and azole inclusive therapy (P = 0.031).
      Survival was significantly longer in patients receiving antifungal therapies
      containing azole than in those who did not receive azole (P = 0.0034).
      CONCLUSIONS: At present, the diagnosis of invasive trichosporonosis depends on
      blood culture studies, and the mortality of this disease is high; however, azole
      therapy and control of blood glucose level, together with hematopoietic recovery
      could help in improving the clinical outcome. When we use antifungals lacking
      anti-Trichosporon activity, sufficient care should be taken to prevent the
      development of breakthrough trichosporonosis.

PMID- 20059531
TI  - A critical reappraisal of treatment response criteria in systemic mastocytosis
      and a proposal for revisions.
AB  - Mast cell disease (MCD) is a hematopoietic stem cell neoplasm that is associated
      with infiltration of one or more organs with cytologically abnormal mast cells
      (MC). MCD is frequently but not always associated with a KIT mutation and, in
      some cases, is associated with clonal expansion of non-MC lineage cells. In
      adults, there is almost always MC infiltration of the bone marrow, which is a
      cardinal feature of systemic mastocytosis (SM). While, as members of the wider
      community of physician scientists, we recognize the contribution of the current
      consensus treatment response criteria for SM, as individuals with more than
      average clinical experience in SM, we would like to point out their limitations
      and engage in a constructive discussion that will hopefully lead to a
      consideration for revisions. We present here an alternative proposal for
      treatment response assessments we believe is more objective, reproducible, and
      importantly, SM-subtype specific, given the recent progress in our understanding
      of the natural history of this disease. We believe this proposal is timely given
      the prospects for new clinical trials in SM, and the related regulatory aspects
      of new drug approval that are currently not adequately addressed. The intent of
      this exercise is not to undermine the complexity of the disease or previous work
      by other investigators, but to come up with ideas for response criteria that are
      more practical and consider meaningful patient outcome.

PMID- 20059533
TI  - Co-inheritance of Hb Hershey [beta70(E14) Ala-->Gly] and Hb La Pommeraie
      [beta133(H11)Val-->Met] in a Sicilian subject.
AB  - OBJECTIVES: This report represents the first observation in Sicily of two rare
      beta-globin gene variants, Hb Hershey [beta70(E14) Ala-->Gly] and Hb La Pommeraie
      [beta133(H11)Val-->Met], found in a 35-year-old male patient from Messina, in the
      north-east of Sicily during population screening for hemoglobinopathies. METHODS:
      The occurrence of the Hb variants was assessed by cation exchange chromatography
      while complete blood counts were obtained using automatic cell counters. Red cell
      lysates were analyzed by electrophoresis at alkaline and acid pH. Stability of
      hemoglobin was checked by the isopropanol precipitation test and by the heat
      tests while inclusion bodies and reticulocyte count were determined by incubation
      of blood samples with brilliant cresyl blue. Molecular analysis was performed by
      DNA sequencing of beta- and alpha-globin genes. RESULTS: We observed an
      abnormally high performance liquid chromatography elution with a slight reduction
      in mean corpuscular volume and mean corpuscular haemoglobin parameters and
      mutations at codon 70 GCC-->GGC (Hb Hershey) and at codon 133 GTG-->ATG (Hb La
      Pommeraie) in beta-globin gene. CONCLUSION: Family analysis of three generations
      demonstrated the presence of these two mutations in trans. So it was possible to
      describe the phenotypes of these variants in a heterozygous state and in double
      heterozygous state.

PMID- 20059535
TI  - Free light chain: a novel predictor of adverse outcome in chronic lymphocytic
      leukemia.
AB  - OBJECTIVES: Chronic lymphocytic leukemia (CLL) is characterized by a highly
      variable clinical course. This retrospective study is planned to assess the
      prognostic value of serum free light chain (sFLC) levels and FLC ratio (FLCR) in
      CLL. METHODS: Quantitative levels of sFLC were measured nephelometrically in sera
      collected at diagnosis. The expressions of ZAP70 and CD38 were quantified by flow
      cytometry. Chromosomal abnormalities were determined by interphase fluorescence
      in situ hybridization (FISH). RESULTS: In a cohort of 101 patients with a median
      follow-up of 29 (1-234) months, sFLC levels were found to be high in 55 patients
      (54.5%). An abnormal FLCR was found in 30 patients (29.7%). FISH-based genetic
      risk groups did not differ significantly with respect to sFLC and FLCR (P >
      0.05). Median time to first treatment was shorter in patients with high sFLC
      levels (P = 0.02). Median overall survival (OS) was shorter in patients with high
      sFLC levels (P = 0.01) and abnormal FLCR (P = 0.05). In patients with early stage
      disease, median OS was shorter in high sFLC (P = 0.03) and abnormal FLCR groups
      (P = 0.048). A relationship was observed between abnormal sFLC levels and CD38
      positivity on logistic regression analysis (P = 0.003; OR: 4.44; 95% CI: 1.66
      11.8). CONCLUSIONS: This study highlighted the adverse prognostic impact of high
      sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage
      patients. Prospective studies are warranted to validate the adverse impact of
      sFLC and FLCR on clinical outcome.

PMID- 20059538
TI  - The animal within: carcinogenesis and the clonal evolution of cancer cells are
      speciation events sensu stricto.
AB  - Heritable genomic variation and natural selection have long been acknowledged as
      striking parallels between evolution and cancer. The logical conclusion, that
      cancer really is a form of speciation, has seldom been expounded directly. My
      purpose is to reexamine the "cancer as species" thesis in the light of current
      attitudes to asexual speciation, and modern analyses of species definitions. The
      chief obstacles to accepting this thesis have been the asexual nature of cancer
      cell reproduction, the instability of the malignant genotype and phenotype, and
      our conditioning that speciation is an extremely rare and imperceptibly
      gradualistic process. However, these are not absolute barriers to the acceptance
      of cancers as bona fide species. Furthermore, although ongoing clonal evolution
      of extant cancers also results in a series of secondary speciation events, the
      initial emergence of a cancer requires a level of taxonomic reclassification even
      beyond the concept of speciation (i.e., phylogenation), and which is almost
      certain to provide a rich source of novel drug targets. The implications of the
      "cancer as species" idea may be as important for biology as for oncology,
      providing as it does an endless supply of observable if accelerated examples of a
      phenomenon once regarded as rare. From the perspective of cancer treatment,
      speciation guarantees the existence of causal molecular mechanisms which may have
      been neglected as exploitable targets for rational therapy; in particular, the
      mediators of metazoan life seem to have substantial overlap with components
      commonly deranged in cancer cells. However, the intractability of the drug
      resistance problem, residing as it does in the inherent plasticity of the genome,
      is traceable back to, and inseparable from, the very origins and nature of life.

PMID- 20059540
TI  - Condition-dependence of the sexually dimorphic transcriptome in Drosophila
      melanogaster.
AB  - Sexually dimorphic traits are by definition exaggerated in one sex, which may
      arise from a history of sex-specific selection-in males, females, or both. If
      this exaggeration comes at a cost, exaggeration is expected to be greater in
      higher condition individuals (condition-dependent). Although studies using small
      numbers of morphological traits are generally supportive, this prediction has not
      been examined at a larger scale. We test this prediction across the transcriptome
      by determining the condition-dependence of sex-biased (dimorphic) gene
      expression. We find that high-condition populations are more sexually dimorphic
      in transcription than low-condition populations. High-condition populations have
      more male-biased genes and more female-biased genes, and a greater degree of
      sexually dimorphic expression in these genes. Also, condition-dependence in male
      biased genes was greater than in a set of unbiased genes. Interestingly, male
      biased genes expressed in the testes were not more condition-dependent than those
      in the soma. By contrast, increased female-biased expression under high condition
      may have occurred because of the greater contribution of the ovary-specific
      transcripts to the entire mRNA pool. We did not find any genomic signatures
      distinguishing the condition-dependent sex-biased genes. The degree of condition
      dependent sexual dimorphism (CDSD) did not differ between the autosomes and the X
      chromosome. There was only weak evidence that rates of evolution correlated with
      CDSD. We suggest that the sensitivity of both female-biased genes and male-biased
      genes to condition may be akin to the overall heightened sensitivity to condition
      that life-history and sexually selected traits tend to exhibit. Our results
      demonstrate that through condition-dependence, early life experience has dramatic
      effects on sexual dimorphism in the adult transcriptome.

PMID- 20059541
TI  - Voltage-gated sodium channel isoform-specific effects of pompilidotoxins.
AB  - Pompilidotoxins (PMTXs, alpha and beta) are small peptides consisting of 13 amino
      acids purified from the venom of the solitary wasps Anoplius samariensis (alpha
      PMTX) and Batozonellus maculifrons (beta-PMTX). They are known to facilitate
      synaptic transmission in the lobster neuromuscular junction, and to slow sodium
      channel inactivation. By using beta-PMTX, alpha-PMTX and four synthetic analogs
      with amino acid changes, we conducted a thorough study of the effects of PMTXs on
      sodium current inactivation in seven mammalian voltage-gated sodium channel
      (VGSC) isoforms and one insect VGSC (DmNa(v)1). By evaluating three components of
      which the inactivating current is composed (fast, slow and steady-state
      components), we could distinguish three distinct groups of PMTX effects. The
      first group concerned the insect and Na(v)1.6 channels, which showed a large
      increase in the steady-state current component without any increase in the slow
      component. Moreover, the dose-dependent increase in this steady-state component
      was correlated with the dose-dependent decrease in the fast component. A second
      group of effects concerned the Na(v)1.1, Na(v)1.2, Na(v)1.3 and Na(v)1.7
      isoforms, which responded with a large increase in the slow component, and showed
      only a small steady-state component. As with the first group of effects, the slow
      component was dose-dependent and correlated with the decrease in the fast
      component. Finally, a third group of effects concerned Na(v)1.4 and Na(v)1.5,
      which did not show any change in the slow or steady-state component. These data
      shed light on the complex and intriguing behavior of VGSCs in response to PMTXs,
      helping us to better understand the molecular determinants explaining isoform
      specific effects.

PMID- 20059542
TI  - Cross-species divergence of the major recognition pathways of ubiquitylated
      substrates for ubiquitin/26S proteasome-mediated proteolysis.
AB  - The recognition of ubiquitylated substrates is an essential element of
      ubiquitin/26S proteasome-mediated proteolysis (UPP), which is mediated directly
      by the proteasome subunit RPN10 and/or RPN13, or indirectly by ubiquitin
      receptors containing ubiquitin-like and ubiquitin-associated domains. By pull
      down and mutagenesis assays, we detected cross-species divergence of the major
      recognition pathways. RPN10 plays a major role in direct recognition in
      Arabidopsis and yeast based on the strong affinity for the long and K48-linked
      ubiquitin chains. In contrast, both the RPN10 and RPN13 homologs play major roles
      in humans. For indirect recognition, the RAD23 and DSK2 homologs (except for the
      human DSK2 homolog) are major receptors. The human RAD23 homolog is targeted to
      the 26S proteasome by the RPN10 and RPN13 homologs. In comparison, Arabidopsis
      uses UIM1 and UIM3 of RPN10 to bind DSK2 and RAD23, respectively. Yeast uses UIM
      in RPN10 and LRR in RPN1. Overall, multiple proteasome subunits are responsible
      for the direct and/or indirect recognition of ubiquitylated substrates in yeast
      and humans. In contrast, a single proteasome subunit, RPN10, is critical for both
      the direct and indirect recognition pathways in Arabidopsis. In agreement with
      these results, the accumulation of ubiquitylated substrates and severe
      pleiotropic phenotypes of vegetative and reproductive growth are associated with
      the loss of RPN10 function in an Arabidopsis T-DNA insertion mutant. This implies
      that the targeting and proteolysis of the critical regulators involved are
      affected. These results support a cross-species mechanistic and functional
      divergence of the major recognition pathways for ubiquitylated substrates of UPP.

PMID- 20059543
TI  - X-ray crystallographic and NMR studies of pantothenate synthetase provide
      insights into the mechanism of homotropic inhibition by pantoate.
AB  - The structural basis for the homotropic inhibition of pantothenate synthetase by
      the substrate pantoate was investigated by X-ray crystallography and high
      resolution NMR spectroscopic methods. The tertiary structure of the dimeric N
      terminal domain of Escherichia coli pantothenate synthetase, determined by X-ray
      crystallography to a resolution of 1.7 A, showed a second molecule of pantoate
      bound in the ATP-binding pocket. Pantoate binding to the ATP-binding site induced
      large changes in structure, mainly for backbone and side chain atoms of residues
      in the ATP binding HXGH(34-37) motif. Sequence-specific NMR resonance assignments
      and solution secondary structure of the dimeric N-terminal domain, obtained using
      samples enriched in (2)H, (13)C, and (15)N, indicated that the secondary
      structural elements were conserved in solution. Nitrogen-15 edited two
      dimensional solution NMR chemical shift mapping experiments revealed that
      pantoate, at 10 mm, bound at these two independent sites. The solution NMR
      studies unambiguously demonstrated that ATP stoichiometrically displaced pantoate
      from the ATP-binding site. All NMR and X-ray studies were conducted at substrate
      concentrations used for enzymatic characterization of pantothenate synthetase
      from different sources [Jonczyk R & Genschel U (2006) J Biol Chem 281, 37435
      37446]. As pantoate binding to its canonical site is structurally conserved,
      these results demonstrate that the observed homotropic effects of pantoate on
      pantothenate biosynthesis are caused by competitive binding of this substrate to
      the ATP-binding site. The results presented here have implications for the design
      and development of potential antibacterial and herbicidal agents.

PMID- 20059544
TI  - Role of TLR4 in the host response to Vibrio vulnificus, an emerging pathogen.
AB  - The incidence of infection with Vibrio vulnificus is increasing due to changing
      ecologic and demographic factors. Most fatal cases are caused by septic shock
      that results from dysregulation of proinflammatory cytokines such as tumor
      necrosis factor-alpha (TNFalpha), presumably due to interaction of V. vulnificus
      components with Toll-like receptors (TLRs). The goal of this study was to
      investigate the role of TLR4 in the host response to V. vulnificus. Results
      obtained using V. vulnificus type strain ATCC 27562 showed that (1) TLR4
      signaling is myeloid differentiation factor 88 dependent and plays a key role in
      TNFalpha production by mouse blood and splenocytes stimulated ex vivo with
      inactivated V. vulnificus cells, (2) TLR4 signaling is deleterious in a mouse
      model of V. vulnificus infection, (3) signaling by TLR(s), exclusive of TLR4, is
      needed to eradicate infection, and (4) the TLR-mediated TNFalpha response plays a
      critical role in determining the outcome of infection. These results suggest that
      blockade of the harmful TLR4-mediated inflammatory response could be a useful
      adjunct to antibiotics for treatment of severe V. vulnificus infection.

PMID- 20059545
TI  - Quantitative PCR methods for RNA and DNA in marine sediments: maximizing yield
      while overcoming inhibition.
AB  - For accurate quantification of DNA and RNA from environmental samples, yield loss
      during nucleic acid purification has to be minimized. Quantitative PCR (qPCR) and
      reverse transcription (RT)-qPCR require a trade-off between maximizing yield and
      removing inhibitors. We compared DNA and RNA yield and suitability for
      quantitative SYBR Green PCR and RT-PCR using the UltraClean and PowerSoil
      extraction kits and a bead-beating protocol with phenol/chloroform extraction
      steps. Purification methods included silica-column-based procedures from the
      MoBio kits, RNeasy MinElute, WizardPlus miniprep columns, and an acrylamide gel
      extraction. DNA and RNA purification with WizardPlus and RNeasy, respectively,
      led to significant losses of nucleic acids and archaeal 16S rRNA or 16S rRNA
      gene, as measured with RiboGreen or PicoGreen, and RT-qPCR or qPCR. Extraction
      and purification of DNA with the MoBio DNA UltraClean and DNA PowerSoil kits also
      decreased the yields slightly, relative to gel purification, in all sediments,
      except those from the deep sea in the Gulf of Mexico. Organic matter in humic
      rich sediments may bind to these silica columns, reducing their nucleic acid
      loading capacity. Purification with gel extraction cleans up organic-rich
      sediment samples sufficiently for quantitative analysis while avoiding the yield
      loss associated with commonly used silica columns.

PMID- 20059546
TI  - Physiological requirements for carbonate precipitation during biofilm development
      of Bacillus subtilis etfA mutant.
AB  - Although the implications of calcium carbonate (CaCO(3)) precipitation by
      microorganisms in natural environments are quite relevant, the physiology and
      genetics of this phenomenon are poorly understood. We have chosen Bacillus
      subtilis 168 as our model to study which physiological aspects are associated
      with CaCO(3) (calcite) formation during biofilm development when grown on
      precipitation medium. A B. subtilis eftA mutant named FBC5 impaired in calcite
      precipitation was used for comparative studies. Our results demonstrate that
      inactivation of etfA causes a decrease in the pH of the precipitation medium
      during biofilm development. Further analysis demonstrated that eftA extrudes an
      excess of 0.7 mol H(+) L(-1) with respect to B. subtilis 168 strain. Using media
      buffered at different pH values, we were able to control calcite formation.
      Because etfA encodes the alpha-subunit of a putative flavoprotein involved in
      fatty acid metabolism, we compared the intracellular levels of NADH among
      strains. Our physiological assay showed that FBC5 accumulated up to 32 times more
      NADH than the wild-type strain. We propose that the accumulation of NADH causes a
      deregulation in the generation of the proton motive force (DeltamicroH(+)) in
      FBC5 producing the acidification.

PMID- 20059547
TI  - Effect of alginate and inulin on intestinal microbial ecology of weanling pigs
      reared under different husbandry conditions.
AB  - The effects of inulin and alginate on intestinal microbial ecophysiology were
      investigated in piglets fed a diet (C) with 0.1% alginate (C+A) or 1.5% inulin
      (C+I) from weaning at day 28. The experiment was performed at an experimental
      farm (EF) and a commercial farm (CF). Digesta was collected from the ileum,
      caecum and colon of four piglets from each group on days 29, 30, 33 and 39. The
      metabolite concentrations changed with age. Colonic and caecal metabolites were
      affected by prebiotic treatment. Changes in microbiota composition were assessed
      by cultivation and denaturing gradient gel electrophoresis (DGGE) of 16S rRNA
      gene fragments. Enterococci increased in C+A at EF and decreased in C+I at both
      farms. Lactobacilli decreased in all segments in the experimental groups on days
      30 and 33. Yeasts in C+I were five times lower at CF than at EF on day 39. The
      richness and diversity of DGGE profiles increased in the experimental groups. The
      evenness of colon digesta-derived DGGE profiles was higher in the experimental
      groups than in C and this situation was reversed in the distal small intestine.
      Multivariate redundancy analysis confirmed the recorded effects. In summary, both
      prebiotics affected the intestinal microbiota, and the changes were more
      pronounced at the CF.

PMID- 20059548
TI  - Recent findings on the viable but nonculturable state in pathogenic bacteria.
AB  - Many bacteria, including a variety of important human pathogens, are known to
      respond to various environmental stresses by entry into a novel physiological
      state, where the cells remain viable, but are no longer culturable on standard
      laboratory media. On resuscitation from this 'viable but nonculturable' (VBNC)
      state, the cells regain culturability and the renewed ability to cause infection.
      It is likely that the VBNC state is a survival strategy, although several
      interesting alternative explanations have been suggested. This review describes
      the VBNC state, the various chemical and physical factors known to induce cells
      into this state, the cellular traits and gene expression exhibited by VBNC cells,
      their antibiotic resistance, retention of virulence and ability to attach and
      persist in the environment, and factors that have been found to allow
      resuscitation of VBNC cells. Along with simple reversal of the inducing stresses,
      a variety of interesting chemical and biological factors have been shown to allow
      resuscitation, including extracellular resuscitation-promoting proteins, a novel
      quorum-sensing system (AI-3) and interactions with amoeba. Finally, the central
      role of catalase in the VBNC response of some bacteria, including its genetic
      regulation, is described.

PMID- 20059549
TI  - How microorganisms avoid phagocyte attraction.
AB  - Microorganisms have developed several mechanisms to modulate the host immune
      system to increase their survival and propagation in the host. Their presence in
      the host is not only revealed by self-produced peptides but also through host
      derived chemokines and active complement fragments. These so-called
      chemoattractants are recognized by G protein-coupled receptors (GPCRs) expressed
      on leukocyte cell membranes. Activation of GPCRs triggers leukocyte activation
      and guides their recruitment to the site of infection. Therefore, GPCRs play a
      central role in leukocyte trafficking leading to microbial clearance. It is
      therefore not surprising that microorganisms are able to sabotage this arm of the
      immune response. Different microorganisms have evolved a variety of tactics to
      modulate GPCR activation. Here, we review the mechanisms and proteins used by
      major human pathogens and less virulent microorganisms that affect GPCR
      signaling. While viruses generally produce receptor and chemoattractant mimics,
      parasites and bacteria such as Staphylococcus aureus, Streptococcus pyogenes,
      Porphyromonas gingivalis, and Bordetella pertussis secrete proteins that affect
      receptor signaling, directly antagonize receptors, cleave stimuli, and even
      prevent stimulus generation. As the large arsenal of GPCR modulators aids
      prolonged microbial persistence in the host, their study provides us a better
      understanding of microbial pathogenesis.

PMID- 20059550
TI  - Bacterial extracellular biology.

PMID- 20059551
TI  - Afr1p mediates activation of the Slt2p MAP kinase induced by pheromone, heat
      shock and hypo-osmotic shock in Saccharomyces cerevisiae.
AB  - In this study, we reinvestigated the role of Afr1p in the regulation of pheromone
      signaling and demonstrated that pheromone signaling was not regulated by Afr1p
      because neither deletion nor overexpression of AFR1 affected alpha-factor-induced
      transcription induction of the FUS1 gene. The enhanced alpha-factor resistance
      resulting from overexpression of AFR1 was dependent on the Slt2p mitogen
      activated protein kinase. We also found that alpha-factor-induced activation of
      Slt2p required Afr1p. In the absence of Afr1p, activation of Slt2p was
      significantly reduced and, in a strain overexpressing Afr1p, the level of Slt2p
      activation was enhanced, indicating that Afr1p may function to mediate cross
      talks between the mating pathway and the cell integrity pathway. Further, Afr1p
      was also required for adequate activation of Slt2p in cells exposed to heat shock
      and hypo-osmotic shock. These results indicated that, in addition to its role in
      establishing pheromone-induced morphogenesis, Afr1p may act as a 'sensor' to
      transduce cell wall stress resulting from different stimuli to the cell integrity
      pathway, leading to Slt2p activation.

PMID- 20059552
TI  - The localization and concentration of the PDE2-encoded high-affinity cAMP
      phosphodiesterase is regulated by cAMP-dependent protein kinase A in the yeast
      Saccharomyces cerevisiae.
AB  - The genome of the yeast Saccharomyces cerevisiae encodes two cyclic AMP (cAMP)
      phosphodiesterases, a low-affinity one, Pde1, and a high-affinity one, Pde2. Pde1
      has been ascribed a function for downregulating agonist-induced cAMP accumulation
      in a protein kinase A (PKA)-governed negative feedback loop, whereas Pde2
      controls the basal cAMP level in the cell. Here we show that PKA regulates the
      localization and protein concentration of Pde2. Pde2 is accumulated in the
      nucleus in wild-type cells growing on glucose, or in strains with hyperactive
      PKA. In contrast, in derepressed wild-type cells or cells with attenuated PKA
      activity, Pde2 is distributed over the nucleus and cytoplasm. We also show
      evidence indicating that the Pde2 protein level is positively correlated with PKA
      activity. The increase in the Pde2 protein level in high-PKA strains and in cells
      growing on glucose was due to its increased half-life. These results suggest
      that, like its low-affinity counterpart, the high-affinity phosphodiesterase may
      also play an important role in the PKA-controlled feedback inhibition of
      intracellular cAMP.

PMID- 20059553
TI  - The role of NCAM in auditory fear conditioning and its modulation by stress: a
      focus on the amygdala.
AB  - Chronic stress in rodents was shown to induce structural shrinkage and functional
      alterations in the hippocampus that were linked to spatial memory impairments.
      Effects of chronic stress on the amygdala have been linked to a facilitation of
      fear conditioning. Although the underlying molecular mechanisms are still poorly
      understood, increasing evidence highlights the neural cell adhesion molecule
      (NCAM) as an important molecular mediator of stress-induced structural and
      functional alterations. In this study, we investigated whether altered NCAM
      expression levels in the amygdala might be related to stress-induced enhancement
      of auditory fear conditioning and anxiety-like behavior. In adult C57BL/6J wild
      type mice, chronic unpredictable stress resulted in an isoform-specific increase
      of NCAM expression (NCAM-140 and NCAM-180) in the amygdala, as well as enhanced
      auditory fear conditioning and anxiety-like behavior. Strikingly, forebrain
      specific conditional NCAM-deficient mice (NCAM-floxed mice that express the cre
      recombinase under the control of the promoter of the alpha-subunit of the calcium
      calmodulin-dependent protein kinase II), whose amygdala NCAM expression levels
      are reduced, displayed impaired auditory fear conditioning which was not altered
      following chronic stress exposure. Likewise, chronic stress in these conditional
      NCAM-deficient mice did not modify NCAM expression levels in the amygdala or
      hippocampus, while they showed enhanced anxiety-like behavior, questioning the
      involvement of NCAM in this type of behavior. Together, our results strongly
      support the involvement of NCAM in the amygdala in the consolidation of auditory
      fear conditioning and highlight increased NCAM expression in the amygdala among
      the mechanisms whereby stress facilitates fear conditioning processes.

PMID- 20059555
TI  - Elongation factors are involved in cytokinesis of sea urchin eggs.
AB  - Cleavage furrows (CFs) have been isolated from dividing sea urchin eggs and the
      protein constituents have been analyzed by two-dimensional gel electrophoresis
      (Fujimoto & Mabuchi, J. Biochem. 122, 518-524, 1997). Two proteins of 51 and 32
      kDa, respectively, have been found to be enriched in the CF preparation. Here, we
      show that these proteins are identical to the protein elongation factor 1alpha
      (EF-1alpha) and 1beta (EF-1beta), respectively. Furthermore, the CF 51-kDa
      protein is identical to the 51-kDa protein which had been isolated as a component
      of the microtubule organizing granules of mitotic sea urchin eggs. The 51-kDa
      protein bundles F-actin in vitro. This activity is suppressed by
      Ca(2+)/calmodulin or GTPgammaS. The 32-kDa protein binds EF-1alpha both in vitro
      and in cell extract, and is shown to suppress the F-actin-bundling activity of
      the 51-kDa protein. Microinjection of a monoclonal antibody against the 51-kDa
      protein or that of His-tagged 32-kDa protein into dividing sea urchin eggs at the
      onset of cleavage leads to failure of cytokinesis. These results strongly suggest
      that EF-1alpha is involved in maintenance of the structure of the contractile
      ring and EF-1beta regulates the F-actin-bundling activity of EF-1alpha.

PMID- 20059556
TI  - Ribosomal RNA gene fragments from fossilized cyanobacteria identified in primary
      gypsum from the late Miocene, Italy.
AB  - Earth scientists have searched for signs of microscopic life in ancient samples
      of permafrost, ice, deep-sea sediments, amber, salt and chert. Until now,
      evidence of cyanobacteria has not been reported in any studies of ancient DNA
      older than a few thousand years. Here, we investigate morphologically,
      biochemically and genetically primary evaporites deposited in situ during the
      late Miocene (Messinian) Salinity Crisis from the north-eastern Apennines of
      Italy. The evaporites contain fossilized bacterial structures having identical
      morphological forms as modern microbes. We successfully extracted and amplified
      genetic material belonging to ancient cyanobacteria from gypsum crystals dating
      back to 5.910-5.816 Ma, when the Mediterranean became a giant hypersaline brine
      pool. This finding represents the oldest ancient cyanobacterial DNA to date. Our
      clone library and its phylogenetic comparison with present cyanobacterial
      populations point to a marine origin for the depositional basin. This
      investigation opens the possibility of including fossil cyanobacterial DNA into
      the palaeo-reconstruction of various environments and could also be used to
      quantify the ecological importance of cyanobacteria through geological time.
      These genetic markers serve as biosignatures providing important clues about
      ancient life and begin a new discussion concerning the debate on the origin of
      late Miocene evaporites in the Mediterranean.

PMID- 20059554
TI  - TPH2 5'- and 3'-regulatory polymorphisms are differentially associated with HPA
      axis function and self-injurious behavior in rhesus monkeys.
AB  - Tryptophan hydroxylase-2 (TPH2) synthesizes neuronal serotonin and is linked to
      numerous behavioral traits. We have previously characterized the functionality of
      polymorphisms (especially 2051A>C) in 3'-untranslated region (3'-UTR) of rhesus
      monkey TPH2 (rhTPH2). This study further assessed the functionality of additional
      polymorphisms (-1605T>C, -1491Tn, -1485(AT)n, -1454A>G, -1325In>Del and -363T>G)
      in rhTPH2 5'-flanking region (5'-FR), and evaluated the effects of rhTPH2 5' and
      3' genotypes on central serotonin turnover, hypothalamic-pituitary-adrenal (HPA)
      axis function and self-injurious behavior (SIB) in 32 unrelated adult male
      monkeys of Indian origin. Haplotypes of the rhTPH2 5'-FR polymorphisms exert a
      significant, cell-dependent effect on reporter gene expression, primarily
      conferred by -1485(AT)n. The -1485(AT)n and 2051A>C polymorphisms interact to
      influence cerebrospinal fluid (CSF) 5-HIAA and plasma adrenocorticotropic hormone
      (ACTH) in the afternoon. While -1485(AT)n exerts significant main effects on the
      afternoon cortisol level and nocturnal HPA negative feedback, 2051A>C has
      significant main effects on the morning cortisol level and cortisol response to
      ACTH challenge, as well as marginally significant main effects on the daytime HPA
      negative feedback and self-biting rate. In addition, the genotype/allele
      frequency of the 5'-FR -1325Ins>Del differed significantly between the self
      wounders and non-wounders, whereas 3'-UTR 2128S>L polymorphism differed
      significantly in genotype/allele frequency between the high- and low-frequency
      biters. This study shows the functionality of rhTPH2 5'-FR polymorphisms, and
      provides evidence for the differential association of rhTPH2 5'-FR and 3'-UTR
      polymorphisms with HPA axis function and SIB. Our findings shed light on the role
      of TPH2 gene variance in physiology and behavioral traits, and also contribute to
      the understanding of the pathophysiology and genetics of SIB.

PMID- 20059557
TI  - Activities and distribution of methanogenic and methane-oxidizing microbes in
      marine sediments from the Cascadia Margin.
AB  - We investigated methane production and oxidation and the depth distribution and
      phylogenetic affiliation of a functional gene for methanogenesis, methyl coenzyme
      M reductase subunit A (mcrA), at two sites of the Integrated Ocean Drilling
      Program Expedition 311. These sites, U1327 and U1329, are respectively inside and
      outside the area of gas hydrate distribution on the Cascadia Margin. Radiotracer
      experiments using (14)C-labelled substrates indicated high potential methane
      production rates in hydrate-bearing sediments [128-223 m below seafloor (mbsf)]
      at U1327 and in sediments between 70 and 140 mbsf at U1329. Tracer-free
      experiments indicated high cumulative methane production in sediments within and
      below the gas hydrate layer at U1327 and in sediments below 70 mbsf at U1329.
      Stable tracer experiments using (13)C-labelled methane showed high potential
      methane oxidation rates in near-surface sediments and in sediments deeper than
      100 mbsf at both sites. Results of polymerase chain reaction amplification of
      mcrA in DNA were mostly consistent with methane production: relatively strong
      mcrA amplification was detected in the gas hydrate-bearing sediments at U1327,
      whereas at U1329, it was mainly detected in sediments from around the bottom
      simulating reflector (126 mbsf). Phylogenetic analysis of mcrA separated it into
      four phylotype clusters: two clusters of methanogens, Methanosarcinales and
      Methanobacteriales, and two clusters of anaerobic methanotrophic archaea, ANME-I
      and ANME-II groups, supporting the activity measurement results. These results
      reveal that in situ methanogenesis in deep sediments probably contributes to gas
      hydrate formation and are inconsistent with the geochemical model that microbial
      methane currently being generated in shallow sediments migrates downward and
      contributes to the hydrate formation. At Site U1327, gas hydrates occurred in
      turbidite sediments, which were absent at Site U1329, suggesting that a
      geological setting suitable for a gas hydrate reservoir is more important for the
      accumulation of gas hydrate than microbiological properties.

PMID- 20059558
TI  - Clinical use of Haemate-P in inherited von Willebrand's disease: a patient with
      type 3 VWD and recurrent menometrorrhagia.

PMID- 20059559
TI  - Safety and efficacy of investigator-prescribed BeneFIX prophylaxis in children
      less than 6 years of age with severe haemophilia B.
AB  - Prophylaxis is increasingly prescribed in treatment of haemophilia and its
      benefit is believed to be most significant for the youngest patients as
      haemophilic arthropathy may be prevented if prophylaxis is initiated prior to
      recurrent haemarthroses. While clinical prophylaxis data are readily available
      for haemophilia A, analogous data for haemophilia B are relatively limited. A
      prospective clinical study of recombinant factor IX (BeneFIX; rFIX), designed to
      allow investigator prescribed prophylaxis according to customary practices, was
      conducted in children <6 years old with severe haemophilia B. Nearly all children
      were prescribed prophylaxis (22/25; 88%) for all or part of their study
      participation. Favourable efficacy and safety profiles were reported. Routine
      prophylaxis with 1 or 2 rFIX infusions per week over an average of greater than 6
      months of therapy resulted in near complete prevention of spontaneous
      breakthrough haemorrhages (<1 per year), with most children (77%) having none,
      including seven patients (32%) who had no bleeding episodes at all. Haemorrhages
      in joints were less common than those outside joints (27% vs. 73% of
      haemorrhages). In a patient population that included children with multiple prior
      haemarthroses, 68% of children had no joint bleeding. Breakthrough haemorrhages
      resolved with 1 or 2 infusions in 89% of episodes. The absence of changes in
      prophylaxis infusion schedules suggests that 1 or 2 rFIX infusion(s) per week
      were well-tolerated by these young patients, including those with (41%) and
      without (59%) central venous access devices. Safety was established by the low
      incidence of treatment-related adverse events.

PMID- 20059560
TI  - Risk-sharing approach for managing factor VIIa reimbursement in haemophilia
      patients with inhibitors.

PMID- 20059561
TI  - Editorial: 'Haemophilia: new challenges and winning directions'.

PMID- 20059562
TI  - Longer-acting factor VIII to overcome limitations in haemophilia management: the
      PEGylated liposomes formulation issue.
AB  - Injected factor VIII (FVIII), the current treatment for haemophilia A, leads to
      major improvements in the quality of life and life expectancy of individuals with
      this disorder. However, because injected FVIII has a short half-life in vivo,
      this strategy has major limitations for highly demanding regimens (e.g.
      prophylaxis, immune tolerance induction, surgery). Newer formulations of longer
      acting FVIII are presently under investigation. The use of low molecular weight
      polyethylene glycol (PEG)-containing liposomes as carriers for recombinant FVIII
      (rFVIII) results in the prolongation of haemostatic efficacy. Data from
      preclinical experiments in mice, early clinical evaluations, and pharmacokinetics
      and pharmacodynamics results indicate that an rFVIII pegylated liposomal
      formulation may provide potential clinical benefit to patients with severe
      haemophilia A by prolonging the protection from bleeding. In light of this
      potential clinical benefit, a multicentre, randomized, active-controlled, non
      inferiority phase II trial with two parallel treatment arms and equal
      randomization after stratification for the presence or absence of target joints
      in patients and for ages >/=18 years vs. <18 years is currently being conducted.
      The study will test the hypothesis that rFVIII-Lip once-weekly prophylaxis is not
      inferior to rFVIII-water for injection thrice-weekly prophylaxis. A total of 250
      patients will be enrolled with severe haemophilia A (<1% FVIII) on on-demand or
      secondary prophylaxis treatment and with documented bleeds or injections during
      the 6 months before study entry. Sixty-four centres in 14 different countries are
      involved in the study; recruitment is underway. In Italy, six centres have
      already included 15 patients (no screening failure). Eight of these patients have
      completed the run-in phase and have begun the home treatment. No unexpected
      serious adverse events have been reported thus far. Data emerging from this phase
      II study will help collect relevant data to overcome current limitations in
      haemophilia management by employing treatment with longer-acting rFVIII.

PMID- 20059563
TI  - Emerging and re-emerging infections at the turn of the millennium.
AB  - After World War II, mankind believed that infectious diseases were on the way to
      being defeated. Unfortunately, they still are the second worldwide cause of
      death. Globalization changes promote the emergence of new infections and
      pandemics; international deliveries and travelling facilitate the dissemination
      of infectious agents; man-induced environmental changes create new opportunities
      for contacts between species, leading to infections in aberrant hosts, including
      man; global warming enables insects, a major vector of pathogens, to thrive in
      more countries. The main pandemics have been caused by viruses, such as HIV and
      novel subtypes of influenza viruses. In addition, prion proteins are a threat.
      The transmission of the Creutzfeld Jakob disease variant through blood
      transfusion and the recent discovery of prion protein in the spleen of a
      haemophilia patient are a matter of further concern. The end of the war against
      infectious diseases is not in sight. Mankind's battle with pathogens has lasted
      millennia and is destined to continue.

PMID- 20059564
TI  - Understanding inhibitor development in haemophilia A: towards clinical prediction
      and prevention strategies.
AB  - Inhibitor development, because of its impact on patients' morbidity and quality
      of life, is presently the most serious complication of haemophilia A treatment.
      The identification of several genetic and non-genetic risk factors may be used
      for the stratification of inhibitor risk and the definition of prevention
      strategies, particularly for patients with a high-risk genetic profile. The most
      extensively studied genetic factor is the type of F8 mutation, i.e. large
      deletions, nonsense mutations and inversions, which are associated with a higher
      risk of inhibitor development. This is the basis for the increased risk in
      patients with inhibitor family history; however, concordance family studies
      showed that factors other than F8 mutations are involved. An emerging role is
      investigated for polymorphisms of immune-regulatory genes that may increase (IL
      10 and TNF-alpha) or reduce (CTLA-4) inhibitor risk and whose heterogeneous
      ethnic distribution may correlate to the higher inhibitor risk in non-caucasian
      patients. A role for FVIII haplotypes, particularly in black haemophiliacs, has
      been recently proposed. Recent studies report an increased inhibitor risk for
      initial intensive treatments (surgery or severe bleeds requiring high-dose and/or
      prolonged treatment, presence of danger signals), whereas regular prophylaxis
      (absence of danger signals) exerts a protective effect. A clinical score
      including the type of F8 mutation, family history of inhibitors and intensive
      treatment has been recently validated for predicting inhibitor risk. Because of
      the lack of useful data regarding the role of different types of FVIII
      concentrates, the stratification of risk in patients starting replacement
      treatment together with the careful evaluation of indications, doses and duration
      of treatment at first exposures and further efforts for overcoming barriers to
      early implementation of prophylaxis are encouraged, particularly for patients
      with a predictable high inhibitor risk.

PMID- 20059565
TI  - Venous access in haemophilic children: choice and management.
AB  - Current haemophilia treatment in children is based on regular intravenous
      infusions of concentrates for prolonged periods, according to prophylaxis
      regimens or immune tolerance induction treatment, in cases of inhibitor
      development. Therefore, a stable and uncomplicated venous access is required and
      as such peripheral veins represent the preferred option. However, frequent
      infusions in the home setting can be problematic in very young children and for
      this reason, central venous access devices (CVADs) have been widely used to
      improve treatment feasibility. Unfortunately CVADs' use is associated with a high
      rate of complications, and infections and thrombotic occlusion can influence
      treatment outcome by causing unwanted treatment interruption. CVADs can be
      grouped into three main categories: external non-tunnelled, external tunnelled
      and fully implantable devices known as ports. The management of CVADs at home
      often represents a challenge because a strict adherence to sterile procedures is
      required. Indeed, the incidence of infections with ports is much lower than that
      reported for external devices; however, ports carry the inconvenience of needle
      sticks. More recently, arteriovenous fistula was shown to be a suitable
      alternative to CVADs because it is easy to use and is associated with a lower
      rate of complication.

PMID- 20059566
TI  - Arteriovenous fistula as stable venous access in children with severe
      haemophilia.
AB  - Treatment for children with severe haemophilia is based on prophylaxis and, if
      inhibitors occur, on immune tolerance induction (ITI). Both regimens require
      frequent infusions at early ages and therefore an adequate venous access is
      essential. Peripheral veins represent the best option; however, central venous
      catheters (CVCs) have been used to facilitate regular treatment. Unfortunately,
      survival of CVCs is affected by infectious and/or thrombotic complications that
      often lead to premature removal and consequent treatment discontinuation. This
      aspect may have an impact on treatment outcome, especially in the case of ITI. In
      light of this, internal arteriovenous fistula (AVF) has been proposed as an
      alternative option because of a lower rate of infectious complications. Moreover,
      AVF is easy to use in the home setting and is well accepted by children and
      parents. The possible complications are postoperative haematoma and transient
      symptoms of distal ischaemia; one case of symptomatic thrombosis has been
      reported to date. Other complications include loss of patency, aneurysmatic
      dilatation and limb dysmetria. A regular follow-up is mandatory to allow early
      remedial interventions. Surgical AVF dismantlement is recommended as soon as
      transition to peripheral vein access is possible.

PMID- 20059567
TI  - The use of central venous catheters in haemophilia patients.
AB  - Summary. Central venous access devices (CVADs) play an important role in the
      management of haemophilia patients requiring repeated and/or urgent
      administration of coagulation factor concentrates. In this article, we summarize
      current knowledge regarding the use of central venous catheters in these
      patients, indicating advantages and disadvantages of both fully implantable and
      external tunnelled CVADs. Finally, we describe our personal experience on the use
      of the external tunnelled catheter Broviac.

PMID- 20059568
TI  - Does the frequency of pay-for-performance payment matter?--Experience from a
      randomized trial.
AB  - OBJECTIVE: To examine the effects of incentive payment frequency on quality
      measures in a physician-specific pay-for-performance (P4P) experiment. STUDY
      SETTING: A multispecialty physician group practice. STUDY DESIGN: In 2007, all
      primary care physicians (n=179) were randomized into two study arms differing by
      the frequency of incentive payment, either four quarterly bonus checks or a
      single year-end bonus (maximum of U.S.$5,000/year for both arms). DATA
      COLLECTION/EXTRACTION METHODS: Data were extracted from electronic health
      records. Quality measure scores between the two arms over four quarters were
      compared. PRINCIPAL FINDINGS: There was no difference between the two arms in
      average quality measure score or in total bonus amount earned. CONCLUSIONS:
      Physicians' responses to a P4P program with a small maximum bonus do not differ
      by frequency of bonus payment.

PMID- 20059569
TI  - Barriers and facilitators of weight management: perspectives of Arab women at
      risk for type 2 diabetes.
AB  - Obesity and associated chronic diseases, such as type 2 diabetes, are highly
      prevalent in the United Arab Emirates (UAE). This qualitative study explored
      weight management behaviours and perceptions of women who are at increased risk
      for type 2 diabetes through focus group interviews. A total of 75 Emirati
      national women (age, 20-60 years) considered high risk for type 2 diabetes
      participated in eight focus groups. Purposive sampling was used to recruit women
      from primary healthcare centres (PHCs) in Al Ain, UAE. Qualitative research
      methodology involving a modified approach to grounded theory was used to guide
      data collection and analysis. Focus group interviews transcripts were
      thematically analyzed using NVivo software. A number of personal, social and
      physical environmental themes emerged as both barriers and enablers that are
      consistent with the social ecological model of health promotion. Low motivation,
      lack of social support, competing demands, lack of culturally-sensitive exercise
      facilities and sociocultural norms that restrict outdoor physical activities were
      the main barriers cited by the participants. On the other hand, social support,
      such as having other women to walk with, helped them stay physically active.
      Suggestions from the participants included enhancing social support for women,
      greater access to dietitians and nutrition information, and increasing
      availability of culturally-sensitive exercise facilities. This study provides
      valuable information in the development of culturally congruent healthy weight
      promotion programmes for women at risk for type 2 diabetes in the UAE and has
      implications for obesity intervention programmes for women in other Arabian Gulf
      countries.

PMID- 20059571
TI  - Microalbuminuria predicts overt proteinuria among patients with HIV infection.
AB  - BACKGROUND: This study examines the association between microalbuminuria and the
      development of proteinuria among HIV-infected persons. METHODS: A total of 948
      subjects provided urine samples for albumin, protein and creatinine measurements
      semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of
      >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350
      mg/mg. The progression from microalbuminuria to proteinuria was described.
      RESULTS: At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2%
      had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria
      and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts
      (P=0.02 comparing subjects without abnormal urine protein excretion to subjects
      with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to
      subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04,
      respectively). Among 658 subjects with normal urine protein, 82.7% continued to
      have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed
      proteinuria. Subjects without baseline proteinuria (i.e. either normal protein
      excretion or microalbuminuria) who developed proteinuria were more likely to have
      microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma
      HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate
      analysis, only microalbuminuria remained associated with the development of
      proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001).
      CONCLUSION: Microalbuminuria predicts the development of proteinuria among HIV
      infected persons. Because proteinuria has been linked to poorer outcomes,
      strategies to affect microalbuminuria should be tested.

PMID- 20059570
TI  - Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with
      cardiovascular disease risk factors.
AB  - OBJECTIVE: People living with HIV infection are at increased risk for developing
      cardiovascular disease (CVD). Safe and effective interventions for lowering CVD
      risk in HIV infection are high priorities. We conducted a prospective,
      randomized, controlled study to evaluate whether a yoga lifestyle intervention
      improves CVD risk factors, virological or immunological status, or quality of
      life (QOL) in HIV-infected adults relative to standard of care treatment in a
      matched control group. METHODS: Sixty HIV-infected adults with mild-moderate CVD
      risk were assigned to 20 weeks of supervised yoga practice or standard of care
      treatment. Baseline and week 20 measures were: 2-h oral glucose tolerance test
      with insulin monitoring, body composition, fasting serum lipid/lipoprotein
      profile, resting blood pressures, CD4 T-cell count and plasma HIV RNA, and the
      Medical Outcomes Study Short Form (SF)-36 health-related QOL inventory. RESULTS:
      Resting systolic and diastolic blood pressures improved more (P=0.04) in the yoga
      group (-5 +/- 2 and -3 +/- 1 mmHg, respectively) than in the standard of care
      group (+1 +/- 2 and+2 +/- 2 mmHg, respectively). However, there was no greater
      reduction in body weight, fat mass or proatherogenic lipids, or improvements in
      glucose tolerance or overall QOL after yoga. Immune and virological status was
      not adversely affected. CONCLUSION: Among traditional lifestyle modifications,
      yoga is a low-cost, simple to administer, nonpharmacological, popular behavioural
      intervention that can lower blood pressure in pre-hypertensive HIV-infected
      adults with mild-moderate CVD risk factors.

PMID- 20059572
TI  - Risks for methicillin-resistant Staphylococcus aureus colonization or infection
      among patients with HIV infection.
AB  - BACKGROUND: Risks for methicillin-resistant Staphylococcus aureus (MRSA) among
      those with HIV infection have been found to vary, and the epidemiology of USA-300
      community-acquired (CA) MRSA has not been adequately described. METHODS: We
      conducted a retrospective review of HIV-infected out-patients from January 2002
      to December 2007 and employed multivariate logistic regression (MLR) to identify
      risks for MRSA colonization or infection. Pulsed-field gel electrophoresis (PFGE)
      was used to identify USA-300 strains. RESULTS: Seventy-two (8%) of 900 HIV
      infected patients were colonized or infected with MRSA. MLR identified antibiotic
      exposure within the past year [odds ratio (OR) 3.4; 95% confidence interval (CI)
      1.5-7.7] and nadir CD4 count <200 cells/microL (OR 2.5; 95% CI 1.2-5.3) as risks
      for MRSA colonization or infection. Receipt of antiretroviral therapy (ART)
      within the past year was associated with decreased risk (OR 0.16; 95% CI 0.07
      0.4). Eighty-nine percent of available strains were USA-300. MLR identified skin
      or soft tissue infection (SSTI) as the only predictor for infection with USA-300
      (OR 5.9; 95% CI 1.4-24.3). CONCLUSION: Significant risks for MRSA among HIV
      infected patients were CD4 count nadir <200 cells/microL and antibiotic exposure.
      Only the presence of an SSTI was associated with having USA-300, and thus the use
      of patient characteristics to predict those with USA-300 was limited. In
      addition, ART within the previous year significantly reduced the risk of MRSA
      colonization or infection.

PMID- 20059574
TI  - British HIV Association guidelines for the management of coinfection with HIV-1
      and hepatitis B or C virus 2010.

PMID- 20059573
TI  - Mode of delivery in HIV-infected pregnant women and prevention of mother-to-child
      transmission: changing practices in Western Europe.
AB  - OBJECTIVES: The aim of the study was to examine temporal and geographical
      patterns of mode of delivery in the European Collaborative Study (ECS), identify
      factors associated with elective caesarean section (CS) delivery in the highly
      active antiretroviral therapy (HAART) era and explore associations between mode
      of delivery and mother-to-child transmission (MTCT). METHODS: The ECS is a cohort
      study in which HIV-infected pregnant women are enrolled and their infants
      prospectively followed. Data on 5238 mother-child pairs (MCPs) enrolled in
      Western European ECS sites between 1985 and 2007 were analysed. RESULTS: The
      elective CS rate increased from 16% in 1985-1993 to 67% in 1999-2001, declining
      to 51% by 2005-2007. In 2002-2004, 10% of infants were delivered vaginally,
      increasing to 34% by 2005-2007. During the HAART era, women in Belgium, the
      United Kingdom and the Netherlands were less likely to deliver by elective CS
      than those in Italy and Spain [adjusted odds ratio (AOR) 0.07; 95% confidence
      interval (CI) 0.04-0.12]. The MTCT rate in 2005-2007 was 1%. Among MCPs with
      maternal HIV RNA<400 HIV-1 RNA copies/mL (n=960), elective CS was associated with
      80% decreased MTCT risk (AOR 0.20; 95% CI 0.05-0.65) adjusting for HAART and
      prematurity. Two infants born to 559 women with viral loads <50 copies/mL were
      infected, one of whom was delivered by elective CS (MTCT rate 0.4%; 95% CI 0.04
      1.29). CONCLUSIONS: Our findings suggest that elective CS prevents MTCT even at
      low maternal viral loads, but the study was insufficiently powered to enable a
      conclusion to be drawn as to whether this applies for viral loads <50 copies/mL.
      Diverging mode of delivery patterns in Europe reflect uncertainties regarding the
      risk-benefit balance of elective CS for women on successful HAART.

PMID- 20059575
TI  - 1,25-dihydroxyvitamin D3 enhances the ability of transferred CD4+ CD25+ cells to
      modulate T helper type 2-driven asthmatic responses.
AB  - The severity of allergic diseases may be modified by vitamin D. However, the
      immune pathways modulated by the active form of vitamin D, 1,25-dihydroxyvitamin
      D(3) [1,25(OH)(2)D(3)], are yet to be fully elucidated. In this study, naturally
      occurring CD4(+) CD25(+) cells from the skin-draining lymph nodes (SDLN) of mice
      treated with topical 1,25(OH)(2)D(3) had an increased ability to suppress T
      helper type 2 (Th2) -skewed immune responses. CD4(+) CD25(+) cells transferred
      from mice treated with topical 1,25(OH)(2)D(3) into ovalbumin (OVA) -sensitized
      mice challenged intranasally with OVA 18 hr later, significantly suppressed the
      capacity of airway-draining lymph node (ADLN) cells to proliferate and secrete
      cytokines in response to further OVA stimulation ex vivo. The CD4(+) CD25(+)
      cells from 1,25(OH)(2)D(3)-treated mice also reduced airway hyperresponsiveness
      and the proportions of neutrophils and eosinophils in bronchoalveolar lavage
      fluid (BALF). To test the effect of 1,25(OH)(2)D(3) on cells able to respond to a
      specific antigen, CD4(+) CD25(+) cells were purified from the SDLN of OVA-T-cell
      receptor (TCR) transgenic mice treated 4 days earlier with topical
      1,25(OH)(2)D(3). CD4(+) CD25(+) cells from OVA-TCR mice treated with
      1,25(OH)(2)D(3) were able to alter BALF cell content and suppress ADLN responses
      to a similar degree to those cells from non-transgenic mice, suggesting that the
      effect of 1,25(OH)(2)D(3) was not related to TCR signalling. In summary, topical
      1,25(OH)(2)D(3) increased the regulatory capacity of CD4(+) CD25(+) cells from
      the SDLN to suppress Th2-mediated allergic airway disease. This work highlights
      how local 1,25(OH)(2)D(3) production by lung epithelial cells may modulate the
      suppressive activity of local regulatory T cells.

PMID- 20059576
TI  - Prevention and treatment of experimental autoimmune encephalomyelitis with
      clonotypic CDR3 peptides: CD4(+) Foxp3(+) T-regulatory cells suppress interleukin
      2-dependent expansion of myelin basic protein-specific T cells.
AB  - T-cell receptor (TCR)-derived peptides are recognized by the immune system and
      are capable of modulating autoimmune responses. Using the myelin basic protein
      (MBP) TCR 1501 transgenic mouse model, we demonstrated that TCR CDR3 peptides
      from the transgenic TCR can provide a protective effect when therapy is initiated
      before the induction of experimental autoimmune encephalomyelitis (EAE). More
      importantly, TCR CDR3 peptide therapy can ameliorate the disease when
      administered after EAE onset. Concurrent with the therapeutic effects, we
      observed reduced T-cell proliferation and reduced interleukin-2 (IL-2) levels in
      response to stimulation with MBP-85-99 peptide in splenocyte cultures from mice
      receiving TCR CDR3 peptides compared with that of control mice. Moreover, we
      found that Foxp3(+) CD4 T cells from mice protected with TCR CDR3 peptide are
      preferentially expanded in the presence of IL-2. This is supportive of a proposed
      mechanism where Foxp3(+) T-regulatory cells induced by therapy with MBP-85-99 TCR
      CDR3 peptides limit expansion and the encephalitogenic activity of MBP-85-99
      specific T cells by regulating the levels of secreted IL-2.

PMID- 20059577
TI  - Partial and transient modulation of the CD3-T-cell receptor complex, elicited by
      low-dose regimens of monoclonal anti-CD3, is sufficient to induce disease
      remission in non-obese diabetic mice.
AB  - It has been established that a total of 250 microg of monoclonal anti-mouse CD3
      F(ab')(2) fragments, administered daily (50 microg per dose), induces remission
      of diabetes in the non-obese diabetic (NOD) mouse model of autoimmune diabetes by
      preventing beta cells from undergoing further autoimmune attack. We evaluated
      lower-dose regimens of monoclonal anti-CD3 F(ab')(2) in diabetic NOD mice for
      their efficacy and associated pharmacodynamic (PD) effects, including CD3-T-cell
      receptor (TCR) complex modulation, complete blood counts and proportions of
      circulating CD4(+), CD8(+) and CD4(+) FoxP3(+) T cells. Four doses of 2 microg
      (total dose 8 microg) induced 53% remission of diabetes, similarly to the 250
      microg dose regimen, whereas four doses of 1 microg induced only 16% remission.
      While the 250 microg dose regimen produced nearly complete and sustained
      modulation of the CD3 -TCR complex, lower doses, spaced 3 days apart, which
      induced similar remission rates, elicited patterns of transient and partial
      modulation. In treated mice, the proportions of circulating CD4(+) and CD8(+) T
      cells decreased, whereas the proportions of CD4(+) FoxP3(+) T cells increased;
      these effects were transient. Mice with greater residual beta-cell function,
      estimated using blood glucose and C-peptide levels at the initiation of
      treatment, were more likely to enter remission than mice with more advanced
      disease. Thus, lower doses of monoclonal anti-CD3 that produced only partial and
      transient modulation of the CD3-TCR complex induced remission rates comparable to
      higher doses of monoclonal anti-CD3. Accordingly, in a clinical setting, lower
      dose regimens may be efficacious and may also improve the safety profile of
      therapy with monoclonal anti-CD3, potentially including reductions in cytokine
      release-related syndromes and maintenance of pathogen-specific immunosurveillance
      during treatment.

PMID- 20059578
TI  - Ectodomain shedding of Fcalpha receptor is mediated by ADAM10 and ADAM17.
AB  - FcalphaR (CD89) plays important roles in immunoglobulin A (IgA)-mediated immune
      responses. Soluble forms of FcalphaR (sFcalphaR) are found in the culture
      supernatants of FcalphaR-expressing cells, in human serum and in the serum of
      FcalphaR transgenic mice, and have been suggested to be produced through a
      proteolytic process. However, little is known about the mechanism involved in the
      proteolytic release of sFcalphaR. In this study, we investigated the shedding
      mechanism of FcalphaR and determined the nature of the proteinase involved in
      FcalphaR shedding. In chemical inhibitor assays, shedding of FcalphaR was
      dramatically inhibited by EDTA, EGTA and a broad-spectrum metalloproteinase
      inhibitor, GM6001, suggesting that a metalloproteinase was responsible for
      FcalphaR shedding. Overexpression of dominant-negative mutants of ADAM (a
      disintegrin and metalloproteinase) 10 and ADAM17 markedly inhibited the
      production of sFcalphaR. Finally, knockdown of both endogenous ADAM10 and
      endogenous ADAM17 inhibited FcalphaR shedding, demonstrating that ADAM10 and
      ADAM17 were involved in the shedding of FcalphaR. The characterization of ADAM10
      and ADAM17 as sFcalphaR-releasing enzymes provides a novel insight into the
      molecular mechanism of sFcalphaR production and will help in further elucidation
      of the physiological and pathological roles of sFcalphaR.

PMID- 20059579
TI  - Regulation of eotaxin-3/CCL26 expression in human monocytic cells.
AB  - Eotaxin-3/CCL26 is an agonist for chemokine receptor 3 (CCR3) and a natural
      antagonist for CCR1, CCR2 and CCR5. CCL26 expression by non-haematopoietic cells
      has been well documented; however, no studies to date have demonstrated CCL26
      expression by leucocytes. In this study, we investigated the ability of human
      monocytic cells to produce CCL26 in response to cytokines. We found that
      interleukin-4 (IL-4) increased the expression of CCL26 messenger RNA (mRNA) and
      protein in U937 cells, in human monocytes and in human monocyte-derived
      macrophages. Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) alone did not induce CCL26 expression, yet these pro-inflammatory
      cytokines synergized with IL-4 to increase CCL26 protein expression. Signal
      transducer and activator of transcription 6 (STAT6) was not affected by
      costimulation with TNF-alpha, suggesting that the synergy between IL-4 and TNF
      alpha occurs at a step downstream of STAT6 activation. Co-incubation of
      interferon-gamma (IFN-gamma) with IL-4 had no effect on CCL26 protein release. By
      contrast, pretreatment with IFN-gamma decreased total STAT6 protein, blocked IL-4
      mediated STAT6 phosphorylation and decreased IL-4-mediated CCL26 mRNA expression
      and protein release. These data show that IL-4 and pro-inflammatory cytokines
      such as TNF-alpha, IL-1beta and IFN-gamma regulate CCL26 synthesis in human
      monocytic cells, which may be important in regulating monocyte inflammatory
      responses.

PMID- 20059580
TI  - Temporal and anatomical sensitivities to the aryl hydrocarbon receptor agonist
      2,3,7,8-tetrachlorodibenzo-p-dioxin leading to premature acyclicity with age in
      rats.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates diverse dioxin toxicities. While the acute effects of activation of
      the AhR pathway by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been a focus
      of past study, the role of this pathway in normal physiology and ageing is
      unclear. The purpose of this study was to identify the portion of the
      reproductive axis [ovary vs. hypothalamus and pituitary gland (H-H axis)] and the
      stages of the reproductive lifespan (foetal and early post-natal life vs.
      adolescence and adulthood) that are particularly sensitive to the effects of TCDD
      during female reproductive ageing. Adult pregnant Lewis rat dams were dosed with
      corn oil vehicle or TCDD (50 ng/kg-week by gavage) on days 14 and 21 of gestation
      and post-natal days 7 and 14 to provide in utero and lactational (IUL) exposure
      to pups. Female pups (n = 96) were weaned on post-natal day 21 and dosed with
      TCDD or vehicle weekly. Half of the pups were used as donors for ovary
      transplantation while the remainder were recipients. Following ovary
      transplantation, rats (n = 6-8 per group) received weekly TCDD or vehicle again
      until sacrifice at 8 months of age. Beginning at vaginal opening, reproductive
      cycles were monitored by vaginal cytology for 10 days each month. Blood samples
      were collected at 22.00 h on proestrus to measure concentration of 17beta
      oestradiol in serum. Real-time PCR was used to determine differences in Cyp1a1,
      Cyp19a1, Cyp17a1, LH receptor (LHR), FoxA2 and FoxJ1 genes expression between
      control and remaining groups. IUL exposure of the H-H axis plus adult exposure of
      the whole body to TCDD significantly delayed puberty in females rats. Data
      analysis revealed an accelerated onset of acyclicity by 5 months in all groups
      involving IUL exposure of the developing ovary to TCDD. 17beta-oestradiol was
      significantly decreased in animals receiving TCDD during IUL exposure of the H-H
      axis. CYP1a1 expression was markedly greater in the liver than in ovarian tissue
      and correlated with ongoing TCDD exposure. Aromatase, 17alpha-hydroxylase and LHR
      gene expressions were largely unchanged (or occasionally elevated) by TCDD. FoxA2
      and FoxJ1 mRNAs were similarly of limited value mechanistically, although FoxJ1
      was much higher in TTT females (receiving TCDD as donor, recipient and adult).
      This study reveals a particular sensitivity of the developing ovary to TCDD
      leading to early loss of reproductive function with age.

PMID- 20059581
TI  - Prospective association of low serum total testosterone levels with health care
      utilization and costs in a population-based cohort of men.
AB  - Despite the burgeoning interest in the field of andrology, no studies have
      specifically addressed the impact of serum testosterone levels on healthcare
      utilization and costs. We analysed data from the population-based cohort Study of
      Health in Pomerania (SHIP), Germany, to assess the association of serum
      testosterone levels with self-reported health care utilization and costs at
      baseline and at 5 years follow up. Study sample comprised 2023 men at baseline,
      of whom 1530 men were repeatedly examined. Low and high serum testosterone
      levels, defined according to the age-specific 10th and 90th percentile, were
      compared with reference subjects with serum testosterone levels >=10th -<=90th
      percentile. Two-part econometric models were applied adjusting for socio-economic
      and medical confounders. Cross-sectional models revealed higher numbers of
      outpatient visits and higher costs for both, men with low (+19.1 and +19.9%,
      respectively) and high serum testosterone levels (+25.3 and +30.2%,
      respectively), whereas number of inpatient days and costs were not associated
      with serum testosterone levels. Adjustment for age, educational level, income,
      waist circumference, smoking status, physical activity and alcohol consumption
      did not considerably alter the results. Longitudinal models revealed a
      significant association of low serum testosterone levels with increased number of
      follow-up outpatient visits (age-adjusted: +28.6%) and costs (+38.0%) only. Low
      and high serum testosterone levels were associated with increased short-term
      outpatient health care costs, whereas low serum testosterone levels appear to be
      predictive of long-term outpatient health care costs. Cost-effectiveness studies
      of available treatments are necessary to identify benefits for physicians,
      patients and health care system as a whole.

PMID- 20059582
TI  - Phthalate exposure and asthma in children.
AB  - During the last decades more than 100 000 new chemicals have been introduced to
      the environment. Many of these new chemicals and many common consumer products
      that include these have been shown to be toxic in animal studies and an
      increasing body of evidence suggests that they are also impacting human health.
      Among the suspect chemicals, the endocrine disrupting chemicals (EDCs) are of
      particular concern. One such chemical group is the phthalates, used in soft poly
      vinyl chloride (PVC) material and in a huge number of consumer products. During
      the same period of time that the prevalence of these modern chemicals has
      increased, there has been a remarkable increase in several chronic illnesses,
      including asthma and allergy in children. In this article we outline the
      scientific knowledge on phthalate exposure for asthma and airway diseases in
      children by examining epidemiological and experimental peer review data for
      potential explanatory mechanisms. Epidemiological data point to a possible
      correlation between phthalate exposure and asthma and airway diseases in
      children. Experimental studies present support for an adjuvant effect on basic
      mechanisms in allergic sensitization by several phthalates. Despite variations in
      the experimental design and reported result in the individual studies, a majority
      of published reports have identified adjuvant effects on Th2 differentiation,
      production of Th2 cytokines and enhanced levels of Th2 promoted immunoglobulins
      (mainly IgG1 but also IgE) in mice. A limited amount of data do also suggest
      phthalate-induced enhancement of mast cell degranulation and eosinophilic
      infiltration which are important parts in the early inflammation phase. Thus,
      some of the early key mechanisms in the pathology of allergic asthma could
      possibly be targeted by phthalate exposure. But the important questions of
      clinical relevance of real life exposure and identification of molecular targets
      that can explain interactions largely remain to be answered.

PMID- 20059584
TI  - Evaluation of erectile dysfunction and associated cardiovascular risk using
      structured questionnaires in Chinese type 2 diabetic men.
AB  - Erectile dysfunction (ED) is not uncommon, but frequently underdiagnosed in type
      2 diabetic men. In this study, we aimed to explore the frequency and severity of
      ED in Chinese type 2 diabetic men using a structured questionnaire. We
      furthermore sought to investigate the associations of ED with diabetes-related
      complications and metabolic indices. A consecutive cohort of 313 Chinese type 2
      diabetic men aged between 25 and 76 years attending a diabetic centre were
      recruited between October 2006 and June 2007. Of the study population, the
      frequency of ED was 39.3% according to the National Institutes of Health (NIH)
      Consensus Conference criteria, compared with 84.3% (41.7% of them having moderate
      to severe ED) as diagnosed by International Index of Erectile Function (IIEF-5)
      questionnaire. After adjusting for potential confounding factors by multivariable
      logistic regression, ED defined by NIH criterion was associated with advanced age
      [OR = 1.05 (95% CI 1.01-1.09), p = 0.012], the presence of diabetic retinopathy
      [OR = 2.43 (95% CI 1.27-4.66), p = 0.008] and coronary heart disease [OR = 2.63
      (95% CI 1.21-5.70), p = 0.015]. ED defined by IIEF-5 was associated with advanced
      age [OR = 1.12 (95% CI 1.06-1.17), p < 0.0001], use of insulin therapy [OR = 2.94
      (95% CI 1.12-7.73), p = 0.029] and urinary albumin-creatinine ratio [OR = 2.29
      (95% CI 1.05-5.01), p = 0.037]. In conclusion, ED was highly prevalent in Chinese
      type 2 diabetic men and was associated with multiple cardiovascular risk factors
      and complications. Advanced age, use of insulin therapy, the existence of
      microvascular complications such as retinopathy, albuminuria and coronary heart
      disease were associated with ED. NIH criteria diagnosed a much lower rate of ED
      compared with IIEF-5. Overall, structured questionnaires are useful and objective
      tools to detect ED, which should prompt a comprehensive risk assessment in these
      subjects.

PMID- 20059583
TI  - The effects of an in utero exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin on
      male reproductive function: identification of Ccl5 as a potential marker.
AB  - 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and dioxin-like compounds are widely
      encountered toxic substances suspected of interfering with the endocrine systems
      of humans and wildlife, and of contributing to the loss of fertility. In this
      study, we determined the changes in testicular gene expression caused by in utero
      exposure to TCDD along with the intra-testicular testosterone levels, epididymal
      sperm reserves, daily sperm production (DSP) and testis histology. To this
      purpose, female pregnant Sprague-Dawley rats orally received TCDD (10, 100 or 200
      ng/kg body weight) or vehicle at embryonic day 15, and the offspring was killed
      throughout development. Hepatic Cyp1a1 gene expression was measured in the
      offspring to confirm the exposure to TCDD. The gross histology of the testes and
      intra-testicular testosterone levels were normal among the studied groups. Sperm
      reserves were altered in 67-day-old rats of the TCDD-200 group, but not in 145
      day-old animals or in the other TCDD-exposed groups. Nonetheless, fertility was
      not altered in males of the TCDD-200 group, and the F2 males generated had normal
      sperm reserves and DSP. Microarray analysis permitted the identification of eight
      differentially expressed genes in the 4-week-old testes of the TCDD-200 compared
      with that of the control group (cut-off value +/- 1.40), including the down
      regulated chemokine Ccl5/Rantes. Inhibition of Ccl5/Rantes gene expression was
      observed throughout development in the TCDD-200 group, and at 67 and 145 days in
      the TCDD-100 group (animals of younger ages were not examined). Ccl5/Rantes gene
      expression was mostly confined in Leydig cells. F2 males generated from males of
      the TCDD-200 group had normal levels of Ccl5/Rantes in testis and Cyp1a1 in
      liver, which might indicate that Ccl5/Rantes is a marker of TCDD exposure in
      testis such as Cyp1a1 in liver. In conclusion, we demonstrated a decrease in
      Ccl5/Rantes RNA levels and a transitory decline in sperm reserves in the testes
      of rats of TCDD-dosed dams.

PMID- 20059585
TI  - Catalase can protect spermatozoa of FSH receptor knock-out mice against oxidant
      induced DNA damage in vitro.
AB  - The aetiology of sperm DNA damage is likely multi-factorial with abnormal
      compaction of nuclear DNA, abortive apoptosis and oxidative stress implicated as
      potential causes of DNA damage. The objective of this study was to evaluate DNA
      damage in spermatozoa from wild-type (WT) and FSH receptor knock-out (FORKO)
      mice, compare the relative susceptibility of spermatozoa from these animals to
      oxidative DNA damage, and examine the protective effect of the antioxidant
      catalase on sperm DNA damage. Epididymal spermatozoa from FORKO mice (n = 5) and
      WT controls (n = 5) were extracted and incubated with or without catalase. Sperm
      DNA damage was assessed immediately after epididymal extraction (time 0 control)
      and following 2-h incubation at 37  degrees C. DNA damage was measured by the
      sperm chromatin structure assay and the results expressed as the %DNA
      fragmentation index or %DFI. Freshly retrieved epididymal spermatozoa from WT
      mice had a significantly lower mean (+/-SD) %DFI than that of FORKO mice (2.7 +/-
      1.8 vs. 6.4 +/- 2.9%, p < 0.05). Prolonged (2-h) incubation of FORKO mice
      spermatozoa resulted in a significant increase in %DFI compared with the time 0
      control (17.9 +/- 9.2% vs. 6.4 +/- 2.9%, respectively, p < 0.05) and the addition
      of catalase protected these spermatozoa from DNA damage (9.8 +/- 4.1 vs. 17.9 +/-
      9.2%, respectively, p < 0.05). However, incubation of WT mice spermatozoa did not
      increase %DFI significantly (5.8 +/- 5.0 vs. 2.7 +/- 1.8, respectively, p > 0.05)
      and the addition of catalase (vs. no catalase) did not result in a significant
      reduction in %DFI (5.8 +/- 5.0 vs. 7.7 +/- 6.5%, respectively, p > 0.05). These
      data indicate that catalase may protect sperm nuclear DNA from oxidative stress
      in vitro. The data also demonstrate the differential susceptibility of WT and
      FORKO mice spermatozoa to oxidative stress.

PMID- 20059586
TI  - Matrix metalloproteinase (MMP)-2 and MMP-9 activity and localization during
      ventral prostate atrophy and regrowth.
AB  - Matrix metalloproteinses (MMPs) are enzymes involved in prostatic development,
      growth, disease-induced tissue remodelling and secretory fluid. Although the
      prostate function depends upon androgen regulation, the relationship between MMPs
      and androgen has not been well established. Here, we evaluated MMP-2 and MMP-9
      gelatinolytic activity in association with tissue localization during ventral
      prostate atrophy and regrowth induced by testosterone replacement (TR). Adult
      male Wistar rats were divided into three experimental groups: control, castrated
      (CS) and TR 21 days after castration. Ventral prostate (VP) was excised at 3, 5,
      7 and 21 days after castration in CS group, and at 3, 5, 7 and 10 days after TR
      (4 mg/kg/day) in TR group. The VP was dissected, weighed and processed for
      histology, immunohistochemistry, ultrastructure and zymography analyses.
      Castration elicited the typical parenchymal atrophy and stromal condensation. TR
      induced intense epithelial growth towards the stromal space to restore the
      prostate histoarchitecture. MMP-2 and MMP-9 immunostaining presented intense
      reaction in CS and TR groups, mainly in the epithelial and endothelial cells.
      After TR, a strong immunoreaction for MMP-2 was observed in the activated stromal
      fibroblasts. Zymography showed that MMP-2 and MMP-9 activity, mainly the active
      form, increased after castration. In contrast, TR induced an additional increase
      in MMP-2 activity, but not in MMP-9. In conclusion, the overall behaviour of MMP
      2 and MMP-9 within the prostate under androgen handling is highly complex, as
      each glandular compartment and cell type is affected differently by the
      androgenic status. Prostate regrowth appears to involve a more effective
      participation of MMP-2 in both epithelial and stromal compartments, while MMP-9
      plays a major role in the late prostate atrophy and early regrowth.

PMID- 20059587
TI  - The longevity of different restorations in primary teeth.
AB  - BACKGROUND AND AIM: This paper reviews three published papers and adds results
      from a fourth study which aimed to determine which restorative material would be
      the best alternative(s) to amalgam (AM) in primary teeth. DESIGN: All studies had
      a practice-based design and were part of the routine treatment of children and
      adolescents. The clinicians were assigned which materials to use in a randomised
      matter in the first three studies which lasted for 7-8 years. In the fourth study
      conducted 4 years after the initial studies, the clinicians were free to select
      the restorative materials. RESULTS AND CONCLUSIONS: Resin modified glass ionomer
      (RMGI) and compomer (COM) restorations showed similar longevity compared with AM,
      whereas conventional GI restorations showed significantly shorter longevity. The
      studies indicated that the 'new and improved' materials based on in vitro tests
      did not always show enhanced clinical properties. In the last study, where
      clinicians freely selected the restorative materials they used in their
      practices, seven used COM, one used conventional GI materials and one used a
      combination of the two types of material.

PMID- 20059588
TI  - Oral health-related quality of life of children with oligodontia.
AB  - OBJECTIVES: To assess the functional and psychosocial impact of oligodontia in
      children aged 11-14 years. METHODS: Children aged 11-14 years with oligodontia
      were recruited from orthodontic clinics when they presented for orthodontic
      evaluation. All completed a copy of the Child Perceptions Questionnaire for 11-
      to 14-year olds, a measure of the functional and psychosocial impact of oral
      disorders. Information on the number and pattern of missing teeth for each child
      were obtained from charts and radiographs. RESULTS: Thirty-six children were
      included in the study. The number of missing teeth ranged from one to 14 (mean =
      6.8). Just over three-quarters of the subjects reported experiencing one or more
      functional and psychosocial impacts 'Often' or 'Everyday/almost everyday'.
      Correlations between scale and sub-scale scores and the number of missing teeth
      were weak and nonsignificant. CONCLUSIONS: Children with oligodontia experience
      substantial functional and psychosocial impacts from the condition. When compared
      with other clinical groups, children with oligodontia appear to have worse oral
      health-related quality of life than children with dental decay and malocclusion,
      but better oral health-related quality of life than children with oro-facial
      conditions.

PMID- 20059589
TI  - The oral health needs of children after treatment for a solid tumour or lymphoma.
AB  - BACKGROUND: With increasing survival rates for childhood cancer, late effects are
      of growing importance. Oral health is central to general health, level of
      nutrition, quality of life, and is significant in the holistic care of children
      during cancer therapy. HYPOTHESIS: The oral health needs of children treated for
      solid tumours/lymphoma will be greater than the general population, groups will
      differ according to tumour and treatment. DESIGN: One hundred and twenty
      patients, 0-17 years, under follow-up from 01/07/06 to 07/02/07 were investigated
      for caries, opacities, microdontia, and gingivitis. Analysis was performed with
      stratification according to tumour and treatment. Comparisons made with the UK
      2003 Child Dental Health Survey. RESULTS: The neuroblastoma group and high-dose
      chemotherapy with stem-cell rescue (HDCSCR) therapy group had increased caries of
      the primary teeth. Chi-squared analysis revealed a statistically significant
      relationship (P < 0.03) between the age at receipt of chemotherapy (<3.5 years)
      and the presence of microdont teeth. CONCLUSION: Oral health care is important
      for all patients particularly those with a neuroblastoma, or who received HDCSCR.
      Patients should be advised about the possibility of microdontia in the permanent
      dentition following chemotherapy under 3.5 years.

PMID- 20059590
TI  - Periodontal disease in mothers indicates risk in their children.
AB  - INTRODUCTION: It is well established that severe periodontitis clusters in
      families, but there are no data about the relationship between mothers with
      chronic periodontitis and their children's periodontal status. OBJECTIVE: To
      evaluate a risk for periodontal diseases in children of periodontally diseased
      and healthy mothers. METHODS: Four study groups were included: (I) 20 female
      patients with untreated generalized severe chronic periodontitis, (II) their
      children (34), (III) 13 periodontally healthy mothers and (IV) their children
      (13). Material was collected from years 2004-2006. The clinical examination
      included registration of visible plaque index, modified gingival index and,
      bleeding sites on probing. Periodontal microbiological samples were obtained from
      all study subjects and the isolates were identified according to morphology and
      biochemical profiles; similar interfamilial pathogens were compared by PCR
      technique. RESULTS: The children of diseased mothers more frequently had
      periodontal diseases, especially gingivitis. In addition, clinical parameters of
      gingival inflammation were more expressed and oral hygiene was worse in this
      group of children. VPI and VPI% of the diseased and healthy mothers differed
      significantly. The most common oral pathogens were P. intermedia/nigrescens and
      A. actinomycetemcomitans. The children of healthy mothers harboured pathogens
      less frequently than the children of diseased mothers. The sharing of P.
      intermedia/nigrescens was more frequent (5 families) than A.
      actinomycetemcomitans (2 families). CONCLUSION: Maternal indicators, such as
      periodontitis, hygiene habits, and periodontal microflora are risk factors for
      childhood periodontal diseases, and might be predictive of future childhood and
      adolescent periodontitis.

PMID- 20059591
TI  - Polarized light and scanning electron microscopic investigation of enamel
      hypoplasia in primary teeth.
AB  - BACKGROUND: Enamel hypoplasia is a developmental disturbance during enamel
      formation, defined as a macroscopic defect in the enamel, with a reduction of the
      enamel thickness with rounded, smooth borders. Information on the microstructural
      level is still limited, therefore further studies are of importance to better
      understand the mechanisms behind enamel hypoplasia. AIM: To study enamel
      hypoplasia in primary teeth by means of polarized light microscopy and scanning
      electron microscopy. METHODS: Nineteen primary teeth with enamel hypoplasia were
      examined in a polarized light microscope and in a scanning electron microscope.
      RESULTS: The cervical and incisal borders of the enamel hypoplasia had a rounded
      appearance, as the prisms in the rounded cervical area of the hypoplasia were
      bent. The rounded borders had a normal surface structure whereas the base of the
      defects appeared rough and porous. CONCLUSIONS: Morphological findings in this
      study indicate that the aetiological factor has a short duration and affects only
      certain ameloblasts. The bottom of the enamel hypoplasia is porous and
      constitutes possible pathways for bacteria into the dentin.

PMID- 20059592
TI  - Effectiveness of a presentation on infant oral health care for parents.
AB  - PURPOSE: The aim of this study was to evaluate an infant oral health education
      programme, using a pre-post test design, for parents attending a paediatric
      clinic. METHODS: The subjects were parents attending the well baby appointments
      at 3, 6, and 9 months of age. The study participants were men and women, all with
      an infant between 3 and 12 months of age. A 16 question assessment in the form of
      a questionnaire was completed immediately before and after the introduction of a
      30 min educational intervention in the form of a PowerPoint presentation and a
      video of infant oral hygiene for parents. The parents completed the questionnaire
      twice (pre-post test design) in the same visit. Recruited parents attended only
      one presentation. The presentation educated parents about infant oral health and
      provided anticipatory guidance. RESULTS: Forty-seven parents or caretakers
      participated in the study. On the pre-test 28% had a score of 70% or less, and on
      the post-test 87% got a score of 88% or better. On the pre-test, 72% had a score
      of 70% or higher, and on the post-test 87% got a score of 88% or higher. Most
      parents (80%) reported that the presentation was helpful and indicated that the
      information would change the way they care for their baby's teeth at home.
      CONCLUSION: This study demonstrated the effectiveness of a 30 min PowerPoint and
      Video presentation in improving the oral health knowledge of parents caring for
      an infant.

PMID- 20059593
TI  - Evaluation of mandibular infiltration versus mandibular block anaesthesia in
      treating primary canines in children.
AB  - OBJECTIVE: The objectives of this study were to determine the effectiveness of
      mandibular infiltration compared with mandibular block in treating primary
      canines in children and to relate the effectiveness to the type of treatment
      performed. METHODS: A total of 89 children, 6-9 years old, requiring identical
      treatment on contralateral mandibular canines were selected. The split mouth
      study design was used. The anaesthetic used in both techniques was 2% lidocaine
      solution with 1 : 80,000 epinephrine. Dental procedures included class III, IV,
      and V restorations, formocresol pulpotomies, and extractions. Child's pain
      reaction and behaviour for each anaesthesia technique and the type of treatment
      were rated at certain intervals of treatment using sounds, motor, and ocular
      changes indicating pain and the Frankl Behaviour Rating Scale. Evaluations were
      made upon injection, probing, rubber dam placement, and during tooth preparation
      and extraction. RESULTS: No statistically significant difference was found
      between the two anaesthetic techniques for either pain or behaviour at all
      evaluation intervals (P > 0.05), during the performance of restorations,
      pulpotomies, or during extractions. CONCLUSIONS: Mandibular infiltration
      anaesthesia is as effective as mandibular block for restoration, pulpotomy, and
      extraction in primary canines. The mandibular infiltration anaesthesia was not
      significantly less painful than the mandibular block.

PMID- 20059594
TI  - A comparison of inhalation sedation agents in the management of children
      receiving dental treatment: a randomized, controlled, cross-over pilot trial.
AB  - AIMS: First, to compare the relative effectiveness of inhalation sedation using
      (A) nitrous oxide and oxygen with (B) nitrous oxide, sevoflurane, and oxygen in
      the management of children receiving dental extractions. Secondly, to determine
      patient and guardian preference between the two sedation techniques. MATERIALS
      AND METHODS: A randomized, controlled, double-blinded, cross-over, pilot clinical
      trial was undertaken. Thirty patients aged 6-15 years, ASA category I or II, who
      required two identical dental extractions with inhalation sedation were
      recruited. At the first session, patients were randomly allocated to receiving
      treatment with sedation Method A or B. At the second session, the alternative
      sedation protocol was employed. RESULTS: Overall, 80% of patients successfully
      completed treatment at both appointments. There was no statistically significant
      difference between either the success rate of the two methods or in guardian
      preference between the two modes of sedation. There was a statistically
      significant difference in patient preference in favour of Method B. CONCLUSIONS:
      The results from this pilot study would suggest no increased benefit, in terms of
      treatment completion, from the additional use of sevoflurane in combination with
      nitrous oxide and oxygen. There was, however, a small but significant patient
      preference in favour of nitrous oxide with sevoflurane and oxygen.

PMID- 20059595
TI  - Oral mucous membrane pemphigoid in a 6-year-old boy: diagnosis, treatment and 4
      years follow-up.
AB  - BACKGROUND: Childhood oral pemphigoid is extremely rare and usually takes the
      form of desquamative gingivitis. CASE REPORT: We describe a 6-year-old boy who
      presented with gingival bleeding, pain, eating difficulty, and peeling of the
      gums. Clinical examination revealed desquamative gingivitis with no extra-oral
      involvement. The diagnosis was established as oral pemphigoid based on the
      clinical, histological, and immunofluorescence findings. Symptoms resolved on
      treatment with occlusive topical corticosteroids. The patient was a carrier of
      the HLA-DQB(1)*0301 allele. CONCLUSION: Mucous membrane pemphigoid should be
      considered in the differential diagnosis of chronic desquamative gingivitis in
      childhood. Occlusive therapy with topical fluocinonide may alleviate the
      symptoms.

PMID- 20059596
TI  - Clinical relevance of single administration of prophylactic antimicrobial agents
      against febrile events after removal of ureteral stents for patients with urinary
      diversion or reconstruction.
AB  - OBJECTIVE: To assess the efficacy of antimicrobial prophylaxis when removing
      ureteral stents after urinary diversion or reconstruction and to establish the
      most appropriate prophylactic protocol to prevent febrile events. METHODS: We
      retrospectively investigated the incidence of febrile events in the two studies.
      Study 1 consisted of 39 patients who received antimicrobial prophylaxis and 31
      who did not. Study 2 included 48 patients who were given oral fluoroquinolone
      (FQ) and 27 who had intramuscular injection of an aminoglycoside (AG). RESULTS:
      In study 1, the incidence of febrile events was significantly lower in patients
      receiving antimicrobial prophylaxis (26.0%) than in those not receiving it
      (51.6%) (P = 0.025, chi(2) test). In study 2 there was a 13% incidence of febrile
      events, which was much lower than the incidence found in study 1. The incidence
      of these events was similar between the two study groups, being 13% for those
      receiving FQ and 15% for those receiving AG. CONCLUSIONS: Prophylactic
      administration of antimicrobials reduces the incidence of febrile events after
      removal of ureteral stents. Both FQ and the AG are equally effective in this
      setting.

PMID- 20059597
TI  - POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes)
      syndrome in China.
AB  - BACKGROUND/AIM: The clinical characteristics of POEMS (polyneuropathy,
      organomegaly, endocrinopathy, M-protein and skin changes) syndrome in China are
      largely unknown. This work thus studied the clinical manifestations of POEMS
      syndrome in China. METHODS: We retrospectively reviewed the medical records of 82
      patients with POEMS syndrome in our hospital and made a comparison with those
      reported outside China. RESULTS: There were 82 patients. Forty (49%) were 45
      years old or younger. Sensorimotor deficits were the common initial symptoms. The
      clinical manifestations are as follows: (i) peripheral neuropathy and abnormal
      electromyogram were seen in all patients (100%); (ii) organomegaly was present in
      72 patients (88%); 61 of them (74%) had splenomegaly; (iii) endocrinopathy was
      present in 74 cases (90%); hypothyroidism was seen in 51 of 70 patients (73%);
      (iv) 60 patients (73%) had monoclonal plasmaproliferative disorder; only 22 of 40
      (55%) had M-protein; (v) skin changes were seen in 71 patients (87%); (vi) 68
      patients (83%) had oedema and effusions; of these, hydropericardium was seen in
      23 patients (28%); (vii) 35 of 55 patients (64%) had abnormal electrocardiogram
      and only 21 of 46 (46%) had bone lesions in X-ray. CONCLUSIONS: POEMS syndrome in
      China has its own distinctive features, parts of which are commoner in the young
      people, the higher frequency of splenomegaly, hypothyroidism, hydropericardium
      and abnormal electrocardiogram, as well as the lower M-protein and bone lesions
      in X-ray.

PMID- 20059598
TI  - Long-term community non-invasive ventilation.
AB  - BACKGROUND: Community non-invasive ventilation (NIV) is increasingly used to
      treat chronic type 2 respiratory failure. Minimal information is published
      regarding patient acceptability or benefit. Records at our institution have
      information gaps. AIMS: To survey patients on chronic NIV - collecting
      demographics, ventilator usage, health-related quality of life, adequacy of
      service provision and compare with clinical best practice. METHODS: Audit tool
      developed and results analysed using descriptive statistics. RESULTS: Of 73
      patients identified, 45 (62%, mean age 55 years) completed the study. Obesity
      hypoventilation (37%) and overlap syndrome (22%) were the commonest indications.
      Reported compliance was high (96% using nocturnal NIV, mean 7.2 h) with 75% on
      treatment >=2 years. Most patients lived at home (77%) and although one-third
      received home care, one-half were working. Nearly all (98%) report positive
      responses, including improved sleep and energy (83%), breathing (42%), driving or
      work (18%). Most (62%) have not been in hospital in the last 12 months. Negative
      aspects included practical issues with machine or mask, loss of intimacy and gaps
      in patient follow up. The provision of practical information, access to well
      informed staff and the establishment of support networks were suggestions for
      service improvement. CONCLUSION: NIV provides a range of symptomatic benefits and
      maintains patients in the community with a reasonably good quality of life. To
      ensure a high level of care and patient satisfaction, several service areas
      warranting further development were identified. Our results should help promote
      this highly effective therapy and aid the development of Australasian NIV service
      guidelines.

PMID- 20059599
TI  - Six-minute walk test: observed adverse events and oxygen desaturation in a large
      cohort of patients with chronic lung disease.
AB  - BACKGROUND: The 6-min walk test (6MWT) is widely used to assess patients with
      chronic lung disease (CLD). Anecdotal reports and studies in small numbers of
      patients with CLD suggest that complications associated with the 6MWT are rare.
      This study reports the incidence of observed adverse events during the 6MWT in
      patients referred to an outpatient pulmonary rehabilitation service. METHODS:
      Seven hundred and forty-one patients with stable CLD (chronic obstructive
      pulmonary disease (COPD), n= 572) completed the 6MWT in accordance with a
      standardized protocol that included continuous monitoring of oxygen saturation
      (SpO(2)) and heart rate (Polar). RESULTS: Adverse events occurred in 43 tests
      (6%). One 6MWT was terminated by the tester because of chest pain and one patient
      developed persistent tachycardia and irregular pulse immediately following the
      test. In 35 tests, the tester instructed the patient to stop walking because of
      profound oxygen desaturation (SpO(2) < 80%). Six patients prematurely terminated
      the 6MWT because of symptoms. Forty-seven per cent (n= 345) of patients exhibited
      significant oxygen desaturation (>=4% fall in SpO(2) to <90%). Pre-exercise
      SpO(2) was a significant predictor of desaturation in the COPD (1.79, 1.54-2.08,
      adjusted odds ratio (OR), 95% confidence intervals) and ILD (OR 1.40, 1.11-1.77)
      cohorts with FEV(1) (forced expiratory volume in 1 s) also a predictor in COPD
      (OR 3.02, 1.77-5.15). CONCLUSION: Profound oxygen desaturation is the most common
      adverse event observed during the 6MWT in patients with stable ILD and COPD. We
      propose that the American Thoracic Society 6MWT guidelines are revised to
      recommend continuous monitoring of SpO(2) during the 6MWT in patients with ILD
      and COPD.

PMID- 20059600
TI  - Echocardiography for the clinician: a practical update.
AB  - Echocardiography is the mainstay of cardiovascular diagnostics, and is the most
      performed test for the evaluation of cardiac function. Critical and costly
      management decisions are based on quantification of left ventricular volumes and
      ejection fraction. Recent advances in echocardiography, such as microsphere
      contrast echocardiography for left ventricular opacification and perfusion
      imaging, three-dimensional transthoracic and trans-oesophageal imaging, strain
      and tissue Doppler imaging, all contribute to improving accuracy and
      reproducibility of these important measurements. Such techniques are now
      routinely available on standard echocardiography equipment in Australian centres
      for daily use. Hand-carried ultrasound devices have been developed, which are
      portable, are affordable and offer increased availability of echocardiography to
      the wider community. Clinicians should be actively encouraged to adopt these
      technologies to improve the diagnostic quality and reproducability of
      echocardiography for our patients. This article provides an overview of important
      recent advances in echocardiographic imaging with an emphasis on their role in
      clinical practice today.

PMID- 20059601
TI  - Acute gout management during hospitalization: a need for a protocol.
AB  - AIM: To review systematically the management of acute gout during
      hospitalization. METHODS: Case-file review of all episodes of acute gout
      occurring in a large tertiary hospital over a 20-month period. RESULTS: Of 134
      acute gout episodes identified, the large majority (118) occurred in patients not
      admitted under the rheumatology unit. Baseline anti-gout medications were
      frequently ceased on admission and in 9% of episodes, no pharmacotherapy was
      prescribed. Delays in initiation of treatment occurred in up to 29% of patients.
      Acute management included anti-inflammatory monotherapy, or combinations of
      colchicine, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids.
      Of patients prescribed colchicine, 26% received >1.5 mg/day and a strong
      correlation was found between colchicine dose and the occurrence of diarrhoea.
      NSAIDs were prescribed in 29% of patients with pre-existing renal impairment.
      Overall, 25% of patients received inappropriate pharmacological management. In
      patients not under the direct care of the rheumatology unit, in-hospital
      rheumatology consultation was sought by the treating unit in 34% of episodes.
      Consultation was sought more frequently in patients with multiple joint
      involvement, but there were no other obvious differences in baseline clinical
      characteristics between cases with or without rheumatology involvement. In cases
      with rheumatology involvement, patients were investigated more frequently, they
      received more pharmacotherapeutic intervention, in particular combination anti
      inflammatory therapy, and they achieved better symptomatic relief and long-term
      follow up. CONCLUSION: Acute gout episodes in hospital are variably investigated
      and treated with frequent suboptimal management. We recommend establishment of a
      hospital-wide protocol to support decision-making regarding investigations,
      treatment and follow up.

PMID- 20059602
TI  - Clinical heterogeneity and prognostic features of South Australian patients with
      anti-synthetase autoantibodies.
AB  - AIM: To determine the clinical, serological and prognostic features of patients
      with autoantibodies against three aminoacyl-transfer RNA synthetases (ARS),
      namely Jo-1 (histidyl-tRNA synthetase), PL-7 (threonyl-tRNA synthetase) and PL-12
      (alanyl-tRNA synthetase) in South Australia. METHODS: Patients with
      autoantibodies against ARS detected by line immunoassay (anti-Jo1, anti-PL7, anti
      PL12) or enzyme-linked immunosorbent assay (anti-Jo1) were identified from
      existing laboratory databases for the period 1994-2009. Demographic, clinical and
      serological data were obtained by retrospective review of patients' medical
      records and laboratory databases. RESULTS: Forty-two patients with autoantibodies
      were identified (anti-Jo1 = 37, anti-PL7 = 4, anti-PL12 = 1). Females were more
      commonly affected than males (M : F = 12:30). Twenty-one patients had
      polymyositis (anti-Jo1 = 17, anti-PL7 = 4), seven dermatomyositis (anti-Jo1 = 6,
      anti-PL12 = 1), 10 overlap syndrome (anti-Jo1 = 10; lupus = 4, scleroderma = 3,
      Sjogren's syndrome = 2 and rheumatoid arthritis = 2) and four had interstitial
      lung disease (ILD) only (anti-Jo1 = 4). ILD was present in 69%, polyarthritis in
      59% and positive anti-nuclear antibody (ANA) in 43% of patients. Concurrence of
      autoantibodies against Ro-52 with Jo-1 was seen in 12 patients. The mean follow
      up period was 8.3 years (95% CI 5.8-10.8) with 12 deaths. Poor prognostic
      indicators were age of onset >60 years (P= 0.001), cancer (P= 0.002), negative
      ANA (P= 0.006) and negative autoantibodies to extractable nuclear antigens (P=
      0.02). CONCLUSION: Patients with autoantibodies against ARS present with varied
      clinical features and occasionally with isolated lung involvement (amyopathic
      ILD). Older age of onset, malignancy and negative immunologic tests are
      predictors of poor prognosis. Concurrence of autoantibodies against Jo-1 and Ro
      52 may reflect a coupling effect during generation of autoimmunity.

PMID- 20059603
TI  - Advances in the management of inflammatory bowel disease.
AB  - Our understanding of inflammatory bowel diseases (IBD) is constantly evolving,
      and many new treatment options have emerged recently. This review critically
      examines the evidence for these new developments and aims to provide an overview
      for medical professionals involved in the care of patients with IBD. Proposed
      changes in the use of aminosalicylates, immunosuppressants and biological agents
      are described, and the evidence for several promising novel agents is reviewed.

PMID- 20059610
TI  - Reproductive competition favours solitary living while ecological constraints
      impose group-living in African striped mice.
AB  - 1. Social groups typically form due to delayed dispersal of adult offspring when
      no opportunities for independent breeding exist, or the costs of dispersal are
      higher than the costs of remaining philopatric. Ecological constraints are
      thought to be a main reason for group-living in animals. 2. Reproductive
      competition within groups can induce high costs of philopatry, and is thought to
      be a main reason for solitary living. 3. Experimental manipulation of
      reproductive competition is difficult. One solution is to compare sociality
      between periods with and without reproductive competition. 4. Here, we show
      empirically in a 8-year field study that striped mice (Rhabdomys pumilio) of both
      sexes were group-living during the breeding season when population density (PD)
      was high but solitary living when PD was low, supporting the ecological
      constraints model. 5. After the breeding season, in the absence of reproductive
      competition, the positive correlation between PD and percentage of group-living
      striped mice was absent. Almost all striped mice were group-living even under
      very low population densities. This supports the reproductive competition model.
      6. Ambient temperature, food availability and predation pressure, did not
      influence sociality. 7. In captivity, the costs of reproductive competition in
      communal groups include female infanticide and aggression between females. 8. We
      conclude that group-living is favoured by constraints imposed through habitat
      saturation and by its benefits (improved thermoregulation by huddling, group
      territoriality and predator avoidance), and that reproductive competition is a
      major force favouring solitary living in striped mice.

PMID- 20059611
TI  - Survival benefits of post-fledging care: experimental approach to a critical part
      of avian reproductive strategies.
AB  - 1. Caring for offspring beyond leaving the nest is an important but under-studied
      part of avian life histories. Theory predicts that prolonged post-fledging
      parental care should yield fitness benefits such as increased fledgling survival.
      Post-fledging care is also costly in terms of time and energy available for
      subsequent reproduction, moult or migration. So far, direct measurements of the
      fitness effects of the duration of post-fledging parental care are lacking. 2. In
      a partial cross-fostering experiment, barn swallow (Hirundo rustica) chicks were
      exchanged among broods close to fledging. Thereby, we separated the effects of
      post-fledging care from those of pre-fledging origin on juvenile survival. 3.
      Prolonging post-fledging care substantially increased juvenile survival up to 3
      weeks post-fledging. Juvenile mortality was maximal in the days following the
      termination of parental care, and prolonging care delayed and reduced this peak
      mortality. Survival of fledglings experiencing 6 days of care was Phi = 0.227,
      whereas fledglings experiencing 14 days of care showed a survival of Phi = 0.571.
      4. Offspring from pairs providing short care showed lower post-fledging survival
      than did offspring from pairs providing long care, irrespective of the actual
      duration of care experienced. This gives evidence for an additional survival
      effect of pre-fledging factors associated with the parental duration of care. 5.
      The results suggest that differential survival in relation to post-fledging
      parental care is a major fitness component. This relationship has profound
      effects on the reproductive trade-offs underlying the evolution of avian life
      histories.

PMID- 20059612
TI  - Left ventricular aneurysm using the Dor technique: mid-term results.
AB  - OBJECTIVE: We have retrospectively analyzed the early and the mid-term results of
      the operations for modified endoventricular circular patch plasty for left
      ventricular aneurysm (LVA) repair in our clinic. PATIENTS AND METHODS: Sixty
      seven cases with anterior LVA were included in the study. Mean age of the
      patients were 64.8 +/- 8.9 (ranged from 51 to 74) years. Fifty-three patients
      were male and 14 female (M:F = 3.8). Preoperative left ventricular ejection
      fraction (LVEF) was 30.8% +/- 4.5%, LV end-diastolic diameter (LVEDD) 6.0 +/- 1.9
      cm, and end-systolic diameter (LVESD) was 4.6 +/- 0.8 cm in average. Coronary
      revascularization was performed in 61 patients and mitral ring annuloplasty in
      five patients. RESULTS: Thirty-day mortality was 5.9%. The surviving 63 patients
      were followed up for 4.3 +/- 2.3 years on average (ranged from 0.2 to 8.5 years),
      adding up to 267.8 patient/years. In the immediate postoperative and long-term
      follow-up, there was a significant improvement in LVEF, LVESD, LVEDD, and mitral
      valvular function. Four patients died in the follow-up with only a single patient
      due to cardiac causes. The five years survival was 87.7% +/- 4.1% and the freedom
      from cardiac death was 98.2% +/- 1.7%. CONCLUSION: LVA repair with Dor procedure
      can be performed with low mortality. With appropriate repair of LVA and coronary
      revascularization, patients may have benefit both for survival and also for
      clinical status.

PMID- 20059613
TI  - Subclavian artery stenosis detected with transit-time flowmeter during OPCAB.

PMID- 20059614
TI  - Differential expression of thiamine biosynthetic genes in yeast strains with high
      and low production of hydrogen sulfide during wine fermentation.
AB  - AIMS: Release of hydrogen sulfide by fermenting yeast is a potential problem in
      wine production, because of its strong organoleptic impact. To identify the
      genetic determinants of sulfide production, we compared the transcriptomes of two
      wine yeast strains with similar oenological properties, but with very different
      levels of sulfide production, UDC522 (high sulfide producer) and P29 (low
      producer). METHODS AND RESULTS: Oenological microfermentations were sampled at
      the peak production of sulfide. Transcription profiles of the two strains were
      analysed by three methods, a cDNA-based array, an oligonucleotide-based array and
      qRT-PCR analysis of selected transcripts. Less than 10% of yeast genes showed
      significant differences between the two strains. High sulfide production
      correlated with a general overexpression of thiamine biosynthesis genes, whereas
      genes linked to the catabolism of sulfur-containing compounds (like amino acids)
      showed no significant expression differences between both strains. CONCLUSIONS:
      Our data suggest a relationship between the thiamine biosynthetic pathway and
      sulfide production during wine fermentation. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides a first hint which indicates that for some yeast
      strains, biosynthesis of thiamine (and perhaps of other sulfur-containing
      compounds) may be more relevant than the general nitrogen metabolism in
      explaining sulfide production by some yeast strains during vinification, defining
      new targets for genetic improvement of wine yeast strains.

PMID- 20059615
TI  - Immunostimulatory activity of potential probiotic yeast strains in the dorsal air
      pouch system and the gut mucosa.
AB  - AIMS: To determine the immunostimulatory activity of 15 presumptive probiotic
      yeast strains in the dorsal air pouch system in comparison with their activity in
      the gut mucosa. METHODS AND RESULTS: Presumptive probiotic yeast strains
      previously isolated from human gastrointestinal tract and Feta cheese were
      further characterized genotypically and biochemically. The Saccharomyces
      cerevisiae 982, Saccharomyces boulardii KK1 and Kluyveromyces lactis 630 strains
      exhibited in the air pouch increased polymorphonuclear cell influx and phagocytic
      activity as well as cytokine production with similar potency as the probiotics
      Ultra levure S. boulardii and Lactobacillus acidophilus NCFB 1748. Oral
      administration of these strains in mice results in differential activation of
      small intestine immune responses concerning IgA and cytokine production as well
      as Toll-like receptor expression. CONCLUSION: Besides the Saccharomyces strains
      982 and KK1, the K. lactis 630 strain could also be considered as a candidate
      probiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: The air pouch model may be used
      as an alternative and rapid method for the discrimination and selection of
      potential probiotic yeast strains.

PMID- 20059616
TI  - Rapid identification and characterization of Vibrio species using whole-cell
      MALDI-TOF mass spectrometry.
AB  - AIMS: Vibrio identification by means of traditional microbiological methods is
      time consuming because of the many biochemical tests that have to be performed to
      distinguish closely related species. This work aimed at evaluating the use of
      MALDI-TOF mass spectrometry for the rapid identification of Vibrio (V.) spp. as
      an advantageous application to rapidly discriminate the most important Vibrio
      spp. and distinguish Vibrio spp. from closely related bacterial species like
      Photobacterium damselae and Grimontia hollisae and other aquatic bacteria like
      Aeromonas spp. METHODS AND RESULTS: Starting from sub-colony amounts of pure
      cultures grown on agar plates, a very simple sample preparation procedure was
      established and combined with a rapid and automated measurement protocol that
      allowed species identification within minutes. Closely related species like
      Vibrio alginolyticus and Vibrio parahaemolyticus or Vibrio cholerae and Vibrio
      mimicus could thus be differentiated by defining signatures of species
      identifying biomarker ions (SIBIs). As a reference method for species designation
      and for determination of relationships between strains with molecular markers,
      partial rpoB gene sequencing was applied. CONCLUSIONS: The MALDI-TOF MS-based
      method as well as the rpoB sequence-based approach for Vibrio identification
      described in this study produced comparable classification results. The
      construction of phylogenetic trees from MALDI-TOF MS and rpoB sequences revealed
      a very good congruence of both methods. SIGNIFICANCE AND IMPACT OF THE STUDY: Our
      results suggest that whole-cell MALDI-TOF MS-based proteometric characterization
      represents a powerful tool for rapid and accurate classification and
      identification of Vibrio spp. and related species.

PMID- 20059617
TI  - Diversity of extracellular proteases among Aeromonas determined by zymogram
      analysis.
AB  - AIMS: The current research was aimed at comparing extracellular proteolytic
      activities and zymogram profiles among Aeromonas spp. METHODS AND RESULTS:
      Extracellular proteases of 47 strains of Aeromonas were analyzed by substrate
      (casein and gelatin) co-polymerized SDS-PAGE, and caseinolytic activity was
      determined using azocasein. Large variation on caseinolytic activity was
      evidenced. In general, the caseinolytic activity of Aeromonas hydrophila strains
      was significantly higher than that of other Aeromonas species. Several
      caseinolytic and gelatinolytic profiles were detected in Aeromonas. Cluster
      analysis allowed separating Aeromonas strains in four and three groups, based on
      their caseinolytic and gelatinolytic profiles, respectively. Although not
      specific patterns were evident, most Aer. hydrophila strains were clustered
      together and differed from Aeromonas caviae strains. The main caseinases of Aer.
      hydrophila were a serine protease with an apparent molecular weight (AMW) of 56
      kDa and a metalloprotease with AMW of 22 kDa. Gelatinase profiles were
      characterized by the presence of high molecular weight metalloproteases (84 and
      93 kDa), although the most active enzyme was a serine protease with AMW of 56
      kDa. Other new caseinases and gelatinases were detected in specific Aeromonas
      strains. CONCLUSIONS: Aeromonas strains exhibited several extracellular
      proteolytic profiles, with a larger inter than intraspecific variation. Moreover,
      zymogram analyses allowed identifying new caseinases and gelatinases in
      Aeromonas. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on the
      intra- and interspecific variation of proteolytic profiles in Aeromonas
      determined by zymogram analysis, including the detection of new caseinases and
      gelatinases in this genus.

PMID- 20059618
TI  - A validated miniaturized MPN method, based on ISO 6579:2002, for the enumeration
      of Salmonella from poultry matrices.
AB  - AIMS: To validate the effectiveness of a miniaturized most probable number method
      (mMPN) in enumerating Salmonella from poultry matrices. METHODS AND RESULTS: A
      MPN was developed, based on the ISO 6579:2002 method using modified semi-solid
      Rappaport-Vassiliadis media as the sole selective medium. The validation of the
      mMPN was shown to not differ significantly from, at the 95% confidence level
      (Student's t-test P = 0.357) to, the traditional 9-tube MPN (tMPN) using pure
      cultures of Salmonella ser. Typhimurium, Infantis, Montevideo, Muenster and
      Salmonella subsp II 1,4,12,27:b:[e,n,x] (Sofia). The validation of naturally and
      artificially contaminated poultry matrices (carcasses, scald tank water, faeces,
      caeca and feed) showed that detection using the mMPN compared well to the ISO
      6572:2002; sensitivity (92%), specificity (97%) and agreement (KAPPA 0.72). The
      quantitative comparison between the tMPN and mMPN methods showed that 92% of
      enumerations were less than +/- 1 log different (Student's t-test = 0.13).
      Financial analysis showed that the mMPN required 64% less media and 56% less
      labour than the tMPN. CONCLUSION: The mMPN is a consistent, easy to automate
      method for the enumeration of Salmonella from different poultry matrices.
      SIGNIFICANCE AND IMPACT OF STUDY: The miniaturized MPN reduces the material and
      labour cost of the method and enables the uniform and accurate measurement of the
      effectiveness of intervention strategies in the control of Salmonella
      colonization of poultry.

PMID- 20059619
TI  - Study of the physicochemical and biological stability of pediocin PA-1 in the
      upper gastrointestinal tract conditions using a dynamic in vitro model.
AB  - AIMS: To evaluate the survival of Pediococcus acidilactici UL5 and its ability to
      produce pediocin PA-1 during transit in an artificial gastrointestinal tract
      (GIT). To investigate the physicochemical and biological stability of purified
      pediocin PA-1 under GIT conditions. METHODS AND RESULTS: Skim milk culture of
      Ped. acidilactici UL5 was fed to a dynamic gastrointestinal (GI) model known as
      TIM-1, comprising four compartments connected by computer-controlled peristaltic
      valves and simulating the human stomach, duodenum, jejunum and ileum. This strain
      tolerated a pH of 2.7 in the gastric compartment, while lower pH reduced its
      viability. Bile salts in the duodenal compartment brought a further 4-log
      reduction after 180 min of digestion, while high viable counts (up to 5 * 10(7)
      CFU ml(-1) fermented milk) of Ped. acidilactici were found in both the jejunal
      and ileal compartments. Pediococcus acidilactici recovered from all four
      compartments was able to produce pediocin at the same level as unstressed cells.
      The activity of the purified pediocin in the gastric compartment was slightly
      reduced after 90 min of gastric digestion, while no detectable activity was found
      in the duodenal, jejunal and ileal compartments during 5 h of digestion. HPLC
      analysis showed partial degradation of the pediocin peptide in the duodenal
      compartment and massive breakdown in the jejunal and ileal compartments.
      CONCLUSIONS: Pediococcus acidilactici UL5 showed high resistance to GIT
      conditions, and its ability to produce pediocin was not affected, suggesting its
      potential as a probiotic candidate. The physicochemical and biological stability
      of pediocin was significantly poor under GIT conditions. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Pediococcus acidilactici UL5 appears to be a potential probiotic
      candidate because its capacity to produce pediocin PA-1 is not affected by the GI
      conditions as well as the strain shows an acceptable survival rate. Meanwhile,
      purified pediocin PA-1 losses activity during GIT transit; microcapsules could be
      used to deliver it to the target site.

PMID- 20059620
TI  - Biodiversity analysis by polyphasic study of marine bacteria associated with
      biocorrosion phenomena.
AB  - AIMS: A polyphasic approach was used to study the biodiversity bacteria
      associated with biocorrosion processes, in particular sulfate-reducing bacteria
      (SRB) and thiosulfate-reducing bacteria (TRB) which are described to be
      particularly aggressive towards metallic materials, notably via hydrogen sulfide
      release. METHODS AND RESULTS: To study this particular flora, an infrared spectra
      library of 22 SRB and TRB collection strains were created using a Common Minimum
      Medium (CMM) developed during this study and standardized culture conditions. The
      CMM proved its ability to allow for growth of both SRB and TRB strains. These
      sulfurogen collection strains were clearly discriminated and differentiated at
      the genus level by fourier transform infrared (FT-IR) spectroscopy. In a second
      step, infrared spectra of isolates, recovered from biofilms formed on carbon
      steel coupons immersed for 1 year in three different French harbour areas, were
      compared to the infrared reference spectra library. In parallel, molecular
      methods (M13-PCR and 16S rRNA gene sequencing) were used to qualitatively
      evaluate the intra- and inter-species genetic diversity of biofilm isolates. The
      biodiversity study indicated that strains belonging to the Vibrio genus were the
      dominant population; strains belonging to the Desulfovibrio genus (SRB) and
      Peptostreptococcaceae were also identified. CONCLUSION: Overall, the combination
      of the FT-IR spectroscopy and molecular approaches allowed for the taxonomic and
      ecological study of a bacterial flora, cultivated on CMM, associated with
      microbiology-induced corrosion (MIC) processes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Via the use of the CMM medium, the culture of marine bacteria (including
      both SRB and TRB bacteria) was allowed, and the implication of nonsulforogen
      bacteria in MIC was observed. Their involvement in the biocorrosion phenomena
      will have to be studied and taken into account in the future.

PMID- 20059621
TI  - Assessment of norovirus contamination in environmental samples from Florianopolis
      City, Southern Brazil.
AB  - AIMS: To assess norovirus (NoV) contamination in aquatic ecosystems in the city
      of Florianopolis, in Southern Brazil, to provide epidemiological data that can
      support actions for environmental contamination control. METHODS AND RESULTS: An
      adsorption-elution method, followed by ultrafiltration, was performed to
      concentrate the viruses. NoV were detected using semi-nested PCR and quantified
      by real-time PCR. From June 2007 to May 2008, NoV were detected in 23% (22/94) of
      the samples analysed, including seawater, drinking water, superficial water
      (creek and brackish lagoon) and treated sewage. The mean viral loads for
      genogroups (G)I and GII in treated sewage samples were 297 and 440 genomic copies
      (gc) l(-1) , respectively, whereas creek water samples contained 2603 and 1361 gc
      l(-1) , respectively. Six samples were sequenced: two samples were GII.4, two
      were GII.2 and two were GI.3. CONCLUSIONS: NoV were detected in all water types
      analysed, demonstrating the widespread contamination of this geographical area
      with several cocirculating strains belonging to GI and GII. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study demonstrates the environmental spread of NoV in
      environmental waters and highlights the potential hazard for human health
      following the consumption of or contact with these waters, which could result in
      waterborne or foodborne acute gastroenteritis.

PMID- 20059622
TI  - Maternal emotion coaching, adolescent anger regulation, and siblings'
      externalizing symptoms.
AB  - BACKGROUND: Increases in externalizing behaviors during the transition to
      adolescence may put children at risk for developing mental disorders and related
      problems. Although children's ability to regulate their emotions appears to be a
      key factor influencing risk for maladjustment, emotion processes during
      adolescence remain understudied. In this longitudinal study, we examined a multi
      level mediational model in which emotion coaching by parents was posited to
      influence the ability of adolescents to regulate their emotions, which in turn
      influences their expression of problem behaviors. METHODS: We recruited a
      representative community sample of 244 families with biological sibling pairs
      comprising a child in late elementary school and a child in middle school.
      Maternal meta-emotion interviews were coded for mother emotion coaching and
      adolescent difficulty with anger. Mothers also completed questionnaires on
      adolescent irritability. Ratings of adolescent problem behaviors were obtained
      from mother and teacher questionnaires completed at two time points. Using
      structural equation modeling, constructs were partitioned into components across
      older and younger siblings to examine shared and nonshared variance and
      contextual effects. RESULTS: Cross-sectional data indicated that mothers' emotion
      coaching of anger was related to better anger regulation in adolescent siblings,
      which was, in turn related to less externalizing behavior. Although support for
      mediational effects was limited in the longitudinal data, both older and younger
      siblings' difficulties in regulating anger predicted adolescent externalizing
      behavior three years later. Additional longitudinal predictors of externalizing
      behavior were observed for younger siblings. In particular, emotion coaching of
      anger by mothers was associated with decreased externalizing behavior, while
      conversely, older siblings' externalizing behavior was associated with increased
      externalizing behavior in the younger siblings over time. CONCLUSIONS: The
      findings highlight the importance of considering family emotion processes in
      understanding adolescent problem behavior. Both maternal emotion coaching of
      adolescent anger and adolescent difficulty in regulating anger influenced
      adolescent externalizing behavior. Emotion coaching interventions seem worthy of
      consideration for enhancing the impact of prevention and intervention programs
      targeting youth externalizing behaviors.

PMID- 20059623
TI  - Genetic and environmental influences on the growth of early reading skills.
AB  - BACKGROUND: Studies have suggested genetic and environmental influences on
      overall level of early reading whereas the larger reading literature has shown
      environmental influences on the rate of growth of early reading skills. This
      study is the first to examine the genetic and environmental influences on both
      initial level of performance and rate of subsequent growth in early reading.
      METHODS: Participants were drawn from the Western Reserve Reading Project, a
      study of 314 twin pairs based in Ohio. Twins were assessed via three annual home
      visits during early elementary school. Assessments included word identification,
      letter identification, pseudoword decoding, expressive vocabulary, phoneme
      awareness, and rapid naming. Measures were analyzed using latent growth curve
      modeling. RESULTS: The heritability of initial performance (latent intercept)
      ranged from h(2) = .38 for word identification to h(2) = .72 for rapid naming.
      Shared environment ranged from c(2) = .11 for rapid naming to c(2) = .62 for word
      identification. The heritability of the rate of subsequent growth (latent slope)
      was statistically significant for rapid naming h(2) = .58 and phoneme awareness
      h(2) = .20. Shared environment accounted for nearly 100% of variance in rate of
      growth for word identification, letter identification and pseudoword decoding,
      and was statistically significant and large for phoneme awareness (c(2) = .80).
      Genetic variance for rapid naming and phoneme awareness latent slopes overlapped
      entirely with genetic variance on the intercepts. In contrast, one-third to two
      thirds of the shared environmental variance on the slope was independent from the
      shared environmental variance on the intercept. CONCLUSIONS: Genetic influences
      were related primarily to those already present at the initial level of
      performance. In contrast, shared environmental influences affecting rate of
      growth were both predicted by and independent from initial levels of performance.
      Results suggested that growth in early reading skills is amenable to family,
      school, or other environmental influences as reading skills develop.

PMID- 20059624
TI  - Editorial: The value of longitudinal studies for understanding continuity and
      variability in development.

PMID- 20059626
TI  - Retraction.

PMID- 20059627
TI  - Editorial: Preschool behaviour problems - over-pathologised or under-identified?
      A developmental psychopathology perspective is needed.

PMID- 20059629
TI  - JCPP editorial conflicts of interest --2010.

PMID- 20059628
TI  - Editorial: 'It's the environment stupid!' On epigenetics, programming and
      plasticity in child mental health.

PMID- 20059630
TI  - Androgenic pattern presentation of scarring and inflammatory alopecia.

PMID- 20059631
TI  - A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes
      for cellulite.
AB  - BACKGROUND: Cellulite is a common complex cosmetic problem for many post
      adolescent women characterised by relief alterations of the skin surface, which
      give the skin an orange-peel appearance. Although genetic factors have been
      suggested to play a role in the development of cellulite, the genetic background
      of this condition remains unclear. We therefore conducted a multi-locus genetic
      study examining the potential associations of candidate gene variants in
      oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid
      metabolism, extracellular matrix homeostasis, inflammation and adipose tissue
      biology, with the risk of cellulite. METHODS: Using a case-control study of 200
      lean women with cellulite and 200 age- and BMI-matched controls (grade 0
      according to Nurnberger-Muller scale), we examined the association of cellulite
      with 25 polymorphisms in 15 candidate genes. RESULTS: Two of the 25 polymorphisms
      were significantly associated with cellulite at the P < 0.01 level. After
      allowance for age, body mass index, the prevalence of contraceptive use and
      smoking in logistic regression analysis, the multivariable-adjusted odds ratios
      for cellulite were 1.19 (95% CI: 1.10-1.51; P < 0.01) for ACE rs1799752 and 0.61
      (95% CI: 0.45-0.88, P < 0.01) for HIF1A rs11549465. CONCLUSIONS: This study,
      which demonstrates an independent role of ACE and HIF1A in predisposing to
      cellulite, may provide novel information on the pathophysiology of this common
      cosmetic problem, and offer a topic for research for novel beautification
      interventions.

PMID- 20059632
TI  - The east-west advancement flap (horizontal advancement flap) to repair a defect
      on the nose ala.
AB  - BACKGROUND: The repair of an alar nasal defect is a frequent challenge for
      dermatologic surgeons for reasons of the high rate of non-melanoma cancers in the
      area. OBJECTIVE: Our aim was to describe the use of an east-west cheek-based flap
      (horizontal advancement flap) to repair a surgical defect on the nose ala.
      METHODS: Benefits and limits of this surgical procedure are evaluated. RESULT:
      The resulting S-shaped scar was well-camouflaged among the natural skin lines
      (melolabial fold and melonasal junction). No architectural distortion of the nose
      resulted from the procedure. CONCLUSION: In selected patients with small-to
      medium-size defects of the nasal ala, the horizontal advancement flap is a
      simple, reliable and aesthetic reconstruction option.

PMID- 20059633
TI  - Relationships between growth and disease resistance in rainbow trout,
      Oncorhynchus mykiss (Walbaum).
AB  - Rainbow trout from 23 families were evaluated for growth and resistance to the
      bacterial coldwater disease (BCWD) caused by Flavobacterium psychrophilum and
      infectious haematopoietic necrosis (IHN) caused by IHN virus. Average family
      weights were between 161 and 263 g with an average of 225 g at 213 days post
      fertilization with specific growth rates ranging from 2.37 to 2.88. Per cent
      survival of fish challenged with F. psychrophilum was between 18% and 100%, while
      for those challenged with IHNV, the range was between 12% and 93%. Significant
      positive correlations were found for end body weight and resistance to IHN (P <
      0.05) and for early body weight and resistance to BCWD (P < 0.1). However, no
      significant correlations were detected between resistance to both pathogens or
      disease resistance and overall genetic diversity or diversity within the major
      histocompatibility locus.

PMID- 20059634
TI  - Detection of infectious pancreatic necrosis virus (IPNV) from asymptomatic
      redbanded seabream, Pagrus auriga Valenciennes, and common seabream, Pagrus
      pagrus (L.), using a non-destructive procedure.
AB  - A non-destructive procedure based on nested RT-PCR and dot-blot hybridization has
      been developed for the detection of asymptomatic IPNV-carrier fish. The pair of
      primers designed for RT-PCR amplified a 599-bp fragment of the pVP2 region within
      the polyprotein gene, resulting in the detection of IPNV genotype III.1. The use
      of a nested RT-PCR allowed the amplification of IPNV genotypes III.1 and I.2. In
      addition, a 191-bp probe was designed for hybridization studies used in
      combination with the nested RT-PCR. The application of the nested RT-PCR to
      analyse blood samples from asymptomatic redbanded seabream, Pagrus auriga, and
      common seabream, P. pagrus, specimens showed a 53.1% and 77.8% prevalence of IPNV
      carriers, respectively. The combination of nested RT-PCR and dot-blot
      hybridization increased the detection rates up to 100% for redbanded seabream and
      94.4% for common seabream. Therefore, the protocol described in this study is
      highly sensitive and specific for the detection of IPNV in asymptomatic carrier
      fish, and, in addition, the results demonstrate the carrier state in two newly
      cultured sparid species in southern Spain.

PMID- 20059635
TI  - A study of gross, histological and blood biochemical changes in rainbow trout,
      Oncorhynchus mykiss (Walbaum), with rainbow trout gastroenteritis (RTGE).
AB  - The mechanisms behind the pathogenesis of rainbow trout gastroenteritis (RTGE)
      are still unknown. This study examined the macroscopic and microscopic changes in
      trout with RTGE (RTGE+), as well as the blood chemistry. A total of 464 rainbow
      trout were sampled from 11 sites in the UK, comprising 152 RTGE+ fish and 330
      random, apparently healthy fish. A case definition for RTGE was assessed by the
      analysis of its agreement with three laboratory tests: histopathology, packed
      cell volume and kidney bacteriology. Cluster analysis indicated the presence of
      three distinct presentations within the population of RTGE+ fish. Cluster A
      included gross signs associated with moribund RTGE+ fish, and clusters B and C
      identified gross signs consistent with concurrent diseases, notably furunculosis,
      enteric redmouth and proliferative kidney disease. The information gained was
      used to select RTGE+ fish without concurrent disease for the analysis of RTGE
      pathogenesis with blood biochemistry. This analysis revealed a severe osmotic
      imbalance and a reduced albumin/globulin ratio as indicatives of selective loss
      of albumin. These findings are compatible with a protein losing enteropathy.

PMID- 20059636
TI  - Genetic diversity and antimicrobial resistance of Flavobacterium psychrophilum
      isolated from cultured rainbow trout, Onchorynchus mykiss (Walbaum), in Spain.
AB  - Flavobacterium psychrophilum is the causative agent of bacterial cold-water
      disease (CWD) and rainbow trout fry syndrome (RTFS) in salmonids. These diseases
      are a major problem in the aquaculture industry in Spain, and a better
      understanding of the epidemiology of F. psychrophilum isolates is necessary to
      improve management strategies. In this study, to investigate genetic variability
      of this bacterium, pulsed-field gel electrophoresis after DNA digestion with
      endonuclease StuI, plasmid profiling analysis and antimicrobial susceptibility
      testing were undertaken with 25 isolates of F. psychrophilum from Spain. These
      isolates were classified into 17 patterns by PFGE analysis, which were grouped
      into four clusters and seven independent branches. Twenty isolates (80%)
      possessed plasmids of 3.5 kb (n = 13) or 5.5 kb (n = 7). No plasmids were
      associated with antibiotic resistance to oxytetracycline (OTC) or florfenicol
      (FLO). Twenty isolates (80%) had minimum inhibitory concentrations (MICs) to OTC
      of between 2.4 and 9.7 microg mL(-1), and all isolates were susceptible to FLO. A
      relationship between the origin of the isolates and PFGE genotypes was found.
      Plasmid profile typing correlated with PFGE profile typing, whereas no
      correlation was found between antimicrobial susceptibility testing and PFGE
      profiles. These results suggest that the population of F. psychrophilum with
      pathogenic potential in northern Spain is quite heterogeneous.

PMID- 20059637
TI  - In vivo transfer of plasmid pRAS1 between Aeromonas salmonicida and Aeromonas
      hydrophila in artificially infected Cyprinus carpio L.
AB  - This study investigated the possible in vivo transfer of plasmid pRAS1 between
      Aeromonas salmonicida and A. hydrophila inhabiting two different organs of
      Cyprinus carpio L. To distinguish transconjugants from naturally occurring
      antibiotic resistant bacteria, twelve luminescent transposon-tagged A. hydrophila
      strains using mini Tn5luxCDABEKm2 transposon were generated. In conjugal transfer
      experiments, fish were conditioned with the donor bacteria and subsequently
      immersed in water containing the recipient strain. Bacteria were recovered from
      gills and intestines and isolated by growth on selective plates. Transconjugants
      were identified by their resistance to the pRAS1 encoded antimicrobials and by
      light emission. In vivo transfer frequencies ranged between 10(-3) and 10(-6) and
      were somewhat lower in intestines, compared to gills. Transfer frequencies were
      also smaller relative to those obtained in vitro. The minimal amount of donor and
      recipient bacteria needed to yield detectable transconjugants in vivo was 1 x
      10(4) CFU mL(-1). Implications of this plasmid transfer in natural settings and
      its possible consequences to human health are discussed.

PMID- 20059638
TI  - Anandamide induces cell death through lipid rafts in hepatic stellate cells.
AB  - BACKGROUND AND AIMS: Anandamide (AEA), the most extensively studied
      endocannabinoid, and its putative cannabinoid receptors, CB1 and CB2, exert a
      variety of physiological and pharmacological effects in chronic liver diseases,
      such as hyperdynamic circulation. Anandamide selectively blocks proliferation and
      induces cell death in hepatic stellate cells (HSC), the key cell type of liver
      fibrogenesis. However, its precise molecular mechanism in rat HSC has not been
      fully elucidated. METHODS: CB1 and CB2 mRNA transcriptions were evaluated by
      reverse transcription polymerase chain reaction; CB1, CB2, phosphoinositide 3
      kinases (PI3K) and protein kinase B (PKB) protein expressions were investigated
      by western blot and/or immunofluorescence. Cell death was detected by Annexin V
      PE/7AAD flow cytometry, lipid raft content by confocal microscopic analysis, cell
      viability by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide
      (MTT) assay, nuclear morphological changes by Hoechst 33258 fluorochrome, and
      inflammatory cytokines interleukin (IL)-2 and IL-6, and tumor necrosis factor
      alpha (TNF-alpha) by enzyme-linked immunosorbent assay. RESULTS: CB1 and CB2
      receptors were detectable in HSC. AEA caused HSC growth inhibition in a
      concentration-dependent manner. Furthermore, a high concentration of AEA (20
      micromol/L) triggered potent cell death-induced necrosis but not apoptosis. None
      of these effects were blocked by CB1 or CB2 receptor antagonist, but by methyl
      beta-cyclodextrin (MCD; 10 mmol/L), a cholesterol depletory agent. AEA
      significantly inhibited PI3K/PKB activity, and increased IL-2, IL-6 and TNF-alpha
      release. CONCLUSION: These results demonstrated that AEA induced HSC necrosis
      through lipid rafts: a possible role of PI3K/PKB signaling pathway downregulation
      and inflammatory factors production. Cholesterol depletion abolished the effects
      of AEA on HSC necrosis.

PMID- 20059640
TI  - Nanomedicine: reshaping clinical practice.

PMID- 20059642
TI  - Nanostructured mesoporous silica matrices in nanomedicine.
AB  - In the last few years the biomedical research field has shown a growing interest
      towards nanostructured mesoporous silica materials, whose chemical composition is
      silica and present nanometric pores. These bioceramics exhibit two important
      features: they can regenerate osseous tissues--the bond bioactivity of these
      materials has been confirmed by the formation of biological-like nanoapatites on
      their surface when in contact with physiological fluids--and they are able to act
      as controlled release systems. Drugs in the nanometre scale can be loaded on
      those matrices and then locally released in a controlled fashion. It is possible
      to chemically modify the silica walls to favour the adsorption of certain
      biomolecules such as peptides, proteins or growth factors. It is even possible to
      design smart biomaterials where the drug is released under an external stimulus.
      Thus, looking at all those properties, a question arises: Have these bioceramics
      good expectations to be used in clinical medical practice? Their
      biocompatibility, bioactivity, capacity to regenerate bone and ability to act as
      controlled release systems of biologically active species have been confirmed. In
      fact, their preliminary in vitro and in vivo essays have been positive. Now it is
      the time to adequate all these properties to the actual clinical problems, and to
      evaluate their efficiency in comparison with materials already known and
      currently employed such as bioglasses.

PMID- 20059643
TI  - Nanomedicine based approaches for the delivery of siRNA in cancer.
AB  - Small interfering RNA (siRNA) technology holds great promise as a therapeutic
      intervention for targeted gene silencing in cancer and other diseases. However,
      in vivo systemic delivery of siRNA-based therapeutics to tumour tissues/cells
      remains a challenge. The major limitations against the use of siRNA as a
      therapeutic tool are its degradation by serum nucleases, poor cellular uptake and
      rapid renal clearance following systemic administration. Several siRNA-based loco
      regional therapeutics are already in clinical trials. Further development of
      siRNAs for anti-cancer therapy depends on the development of safe and effective
      nanocarriers for systemic administration. To overcome these hurdles, nuclease
      resistant chemically modified siRNAs and variety of synthetic and natural
      biodegradable lipids and polymers have been developed to systemically deliver
      siRNA with different efficacy and safety profiles. Cationic liposomes have
      emerged as one of the most attractive carriers because of their ability to form
      complexes with negatively charged siRNA and high in vitro transfection
      efficiency. However, their effectiveness as potential therapeutic carriers is
      limited by potential for pulmonary toxicity. Recently, our laboratories described
      the use of neutral 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine based
      nanoliposomes in murine tumour models. We found this approach to be safe and 10-
      and 30-fold more effective than cationic liposomes and naked siRNA, respectively,
      for systemic delivery of siRNA into tumour tissues. Here, we review potential
      approaches for systemic delivery of siRNA for cancer therapy.

PMID- 20059641
TI  - Lipid-based nanotherapeutics for siRNA delivery.
AB  - RNA interference (RNAi) is a specific gene-silencing mechanism triggered by small
      interfering RNA (siRNA). The application of RNAi in the clinic requires the
      development of safe and effective delivery systems. Inspired by progress with
      lipid-based systems in drug delivery, efforts have been dedicated to the
      development of liposomal siRNA delivery systems. Many of the lipid-based delivery
      vehicles self-assemble with siRNA through electrostatic interactions with charged
      amines, generating multi-lamellar lipoplexes with positively charged lipid
      bilayers separated from one another by sheets of negatively charged siRNA
      strands. Internalization of lipid-based siRNA delivery systems into cells
      typically occurs through endocytosis; accordingly, delivery requires materials
      that can facilitate endosomal escape. The size of the carrier is important as
      carriers <100 nm in diameter have been reported to have higher accumulation
      levels in tumours, hepatocytes and inflamed tissue, whereas larger particles tend
      to be taken up by Kupffer cells or other components of the reticuloendothelial
      system (RES). To reduce RES uptake and increase circulation time, carriers have
      been modified on the surface with hydrophilic materials, such as
      polyethyleneglycol. Herein, we review the molecular and structural parameters of
      lipid-based siRNA delivery systems.

PMID- 20059644
TI  - Cell sheet engineering: a unique nanotechnology for scaffold-free tissue
      reconstruction with clinical applications in regenerative medicine.
AB  - Cell sheet technology (CST) is based on the use of thermoresponsive polymers,
      poly(N-isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in
      such a way as to make its typical thickness <100 nm. In this review, we first
      focus on how the methods of PIPAAm-grafted surface preparations and
      functionalization are important to be able to harvest a functional cell sheet, to
      be further transplanted. Then, we present aspects of tissue mimics and three
      dimensional reconstruction of a tissue in vitro. Finally, we give an overview of
      clinical applications and clinically relevant animal experimentations of the
      technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal
      ulcerations and type 1 diabetes.

PMID- 20059646
TI  - Safety assessment for nanotechnology and nanomedicine: concepts of
      nanotoxicology.
AB  - Nanotechnology, nanomedicine and nanotoxicology are complementary disciplines
      aimed at the betterment of human life. However, concerns have been expressed
      about risks posed by engineered nanomaterials (ENMs), their potential to cause
      undesirable effects, contaminate the environment and adversely affect susceptible
      parts of the population. Information about toxicity and biokinetics of nano
      enabled products combined with the knowledge of unintentional human and
      environmental exposure or intentional delivery for medicinal purposes will be
      necessary to determine real or perceived risks of nanomaterials. Yet, results of
      toxicological studies using only extraordinarily high experimental doses have to
      be interpreted with caution. Key concepts of nanotoxicology are addressed,
      including significance of dose, dose rate, and biokinetics, which are exemplified
      by specific findings of ENM toxicity, and by discussing the importance of
      detailed physico-chemical characterization of nanoparticles, specifically surface
      properties. Thorough evaluation of desirable versus adverse effects is required
      for safe applications of ENMs, and major challenges lie ahead to answer key
      questions of nanotoxicology. Foremost are assessment of human and environmental
      exposure, and biokinetics or pharmacokinetics, identification of potential
      hazards, and biopersistence in cells and subcellular structures to perform
      meaningful risk assessments. A specific example of multiwalled carbon nanotubes
      (MWCNT) illustrates the difficulty of extrapolating toxicological results. MWCNT
      were found to cause asbestos-like effects of the mesothelium following
      intracavitary injection of high doses in rodents. The important question of
      whether inhaled MWCNT will translocate to sensitive mesothelial sites has not
      been answered yet. Even without being able to perform a quantitative risk
      assessment for ENMs, due to the lack of sufficient data on exposure, biokinetics
      and organ toxicity, until we know better it should be made mandatory to prevent
      exposure by appropriate precautionary measures/regulations and practicing best
      industrial hygiene to avoid future horror scenarios from environmental or
      occupational exposures. Similarly, safety assessment for medical applications as
      key contribution of nanotoxicology to nanomedicine relies heavily on nano
      specific toxicological concepts and findings and on a multidisciplinary
      collaborative approach involving material scientists, physicians and
      toxicologists.

PMID- 20059645
TI  - Emerging peptide nanomedicine to regenerate tissues and organs.
AB  - Peptide nanostructures containing bioactive signals offer exciting novel
      therapies of broad potential impact in regenerative medicine. These
      nanostructures can be designed through self-assembly strategies and
      supramolecular chemistry, and have the potential to combine bioactivity for
      multiple targets with biocompatibility. It is also possible to multiplex their
      functions by using them to deliver proteins, nucleic acids, drugs and cells. In
      this review, we illustrate progress made in this new field by our group and
      others using peptide-based nanotechnology. Specifically, we highlight the use of
      self-assembling peptide amphiphiles towards applications in the regeneration of
      the central nervous system, vasculature and hard tissue along with the transplant
      of islets and the controlled release of nitric oxide to prevent neointimal
      hyperplasia. Also, we discuss other self-assembling oligopeptide technology and
      the progress made with these materials towards the development of potential
      therapies.

PMID- 20059647
TI  - The role of nanotoxicology in realizing the 'helping without harm' paradigm of
      nanomedicine: lessons from studies of pulmonary effects of single-walled carbon
      nanotubes.
AB  - Nano-sized materials and nano-scaled processes are widely used in many
      industries. They are being actively introduced as diagnostic and therapeutic in
      biomedicine and they are found in numerous consumer products. The small size of
      nanoparticles, comparable with molecular machinery of cells, may affect normal
      physiological functions of cells and cause cytotoxicity. Their toxic potential
      cannot be extrapolated from studies of larger particles due to unique
      physicochemical properties of nanomaterials. Therefore, the use of nanomaterials
      may pose unknown risks to human health and the environment. This review discusses
      several important issues relevant to pulmonary toxicity of nanoparticles,
      especially single-walled carbon nanotubes (SWCNT), their direct cytotoxic
      effects, their ability to cause an inflammatory response, and induce oxidative
      stress upon pharyngeal aspiration or inhalation. Further, recognition and
      engulfment of nanotubes by macrophages as they relate to phagocytosis and bio
      distribution of nanotubes in tissues and circulation are discussed. The
      immunosuppressive effects of CNT and their significance in increased sensitivity
      of exposed individuals to microbial infections are summarized. Finally, data on
      biodegradation of SWCNT by oxidative enzymes of inflammatory cells are presented
      in lieu of their persistence and distribution in the body.

PMID- 20059648
TI  - Adenovirus-mediated leptin expression normalises hypertension associated with
      diet-induced obesity.
AB  - In our previous study, moderate increases in plasma leptin levels achieved via
      administration of recombinant adenovirus containing the rat leptin cDNA were
      shown to correct the abnormal metabolic profile in rats with diet-induced
      obesity, suggesting that these animals had developed resistance to the metabolic
      effects of leptin, which could be reversed by leptin gene over-expression.
      However, the effect of this therapeutic strategy on blood pressure was not
      investigated. The present study aimed to determine whether a moderate increase of
      endogenous plasma leptin levels affected arterial blood pressure in rats with
      diet-induced obesity and hypertension. The major finding from the present study
      was that the natural rise in plasma leptin with weight-gain is insufficient to
      counterbalance high blood pressure associated with obesity, additional increases
      of circulating leptin levels with adenoviral leptin gene therapy led to
      normalisation of blood pressure in high-fat diet-induced obese and hypertensive
      rats. Mechanistically, the reduction of blood pressure by leptin in obese rats
      was likely independent of alpha-adrenergic and acetylcholinergic receptor
      mediation. This is the first study to demonstrate that further increases in
      circulating leptin levels by leptin gene transfer during obesity could reduce
      blood pressure.

PMID- 20059649
TI  - Influence of the veneering process on the marginal fit of zirconia fixed dental
      prostheses.
AB  - Distortions in the marginal region during manufacture are detrimental to the long
      term success of fixed dental prostheses (FDPs). The aim of the present in vitro
      study was to evaluate changes in marginal fit because of the veneering process of
      four-unit FDPs made from different zirconia materials. Two groups of FDPs with 10
      specimens each were machined from white body zirconia blanks (VITA In-Ceram YZ
      Cubes, KaVo Everest ZS-Blanks) by means of computer-aided design/computer-aided
      manufacturing systems and subsequently sintered to their final density. The
      marginal and internal gaps of the frameworks were determined using a replica
      technique. Afterwards, frameworks were veneered with the recommended ceramics
      (VITA VM9, GC Initial Zr), and fitting accuracy was evaluated again. Statistical
      analyses were performed by Student's t-test with the level of significance chosen
      at 0.05. With one framework/veneering system (Everest ZS-Blanks/Initial Zr), both
      marginal gap (P = 0.019) and internal gap (P = 0.001) at the premolar retainer
      were significantly affected by the veneering process. The resulting distortions
      were directed towards the lumina of the retainers and the mean values of the
      measured gaps decreased by about 23.8 mum (marginal gap) and 27.3 mum (internal
      gap). For the other system (In-Ceram YZ Cubes/VM9), no distortions because of the
      veneering were found. The veneering of zirconia restorations may lead to
      significant changes in the marginal fit, while the combination of core and
      veneering material used influences the resulting distortions.

PMID- 20059650
TI  - Genetic and environmental influences on self-reported G-spots in women: a twin
      study.
AB  - INTRODUCTION: There is an ongoing debate around the existence of the G-spot--an
      allegedly highly sensitive area on the anterior wall of the human vagina. The
      existence of the G-spot seems to be widely accepted among women, despite the
      failure of numerous behavioral, anatomical, and biochemical studies to prove its
      existence. Heritability has been demonstrated in all other genuine anatomical
      traits studied so far. AIM: To investigate whether the self-reported G-spot has
      an underlying genetic basis. METHODS: 1804 unselected female twins aged 22-83
      completed a questionnaire that included questions about female sexuality and
      asked about the presence or absence of a G-spot. The relative contribution of
      genetic and environmental factors to variation in the reported existence of a G
      spot was assessed using a variance components model fitting approach. MAIN
      OUTCOME MEASURES: Genetic variance component analysis of self-reported G-spot.
      RESULTS: We found 56% of women reported having a G-spot. The prevalence decreased
      with age. Variance component analyses revealed that variation in G-spot reported
      frequency is almost entirely a result of individual experiences and random
      measurement error (>89%) with no detectable genetic influence. Correlations with
      associated general sexual behavior, relationship satisfaction, and attitudes
      toward sexuality suggest that the self-reported G-spot is to be a secondary
      pseudo-phenomenon. CONCLUSIONS: To our knowledge, this is the largest study
      investigating the prevalence of the G-spot and the first one to explore an
      underlying genetic basis. A possible explanation for the lack of heritability may
      be that women differ in their ability to detect their own (true) G-spots.
      However, we postulate that the reason for the lack of genetic variation-in
      contrast to other anatomical and physiological traits studied-is that there is no
      physiological or physical basis for the G-spot.

PMID- 20059651
TI  - Psychological determinants of erectile dysfunction: testing a cognitive-emotional
      model.
AB  - INTRODUCTION: Recent studies have shown the impact of sexual dysfunctional
      beliefs, negative cognitive schemas, negative automatic thoughts, and depressed
      affect on male erectile dysfunction. Despite this fact, there are only few
      conceptual models that try to integrate these findings, and more importantly,
      there is a lack of studies that test the validity of those conceptual models.
      AIM: The aim of the present article was to test a cognitive-emotional model for
      erectile dysfunction. Taking previous research findings into account, we
      developed a cognitive-emotional model for erectile disorder (ED) and used path
      analysis to test it. METHODS: A total of 352 men (303 participants from the
      general population and 49 participants with a DSM-IV diagnosis of sexual
      dysfunction) answered a set of questionnaires assessing cognitive and emotional
      variables. MAIN OUTCOME MEASURES: Erectile Function measured by the EF subscale
      of the International Index of Erectile Function, cognitive schemas measured by
      the Questionnaire of Cognitive Schema Activation in Sexual Context, sexual
      beliefs measured by the Sexual Dysfunctional Beliefs Questionnaire, thoughts and
      emotions measured by the Sexual Modes Questionnaire. RESULTS: The effects of the
      main proposed direct predictors explained 55% of the erectile function variance
      (R = 0.74). Most remaining direct effects proposed in the model were also
      statistically significant. The analysis of the absolute residuals showed that
      most of the implied correlations were close to the observed zero order
      correlations, indicated the adjustment of the model to the observed data.
      CONCLUSIONS: These findings support the role played by cognitive and emotional
      factors on the predisposition and maintenance of male erectile dysfunction and
      suggest important implications for assessment and treatment of ED.

PMID- 20059652
TI  - Physical therapy treatment of persistent genital arousal disorder during
      pregnancy: a case report.
AB  - INTRODUCTION: Persistent genital arousal disorder (PGAD) is described as the
      spontaneous, intrusive, and unwanted genital arousal in the absence of sexual
      interest and desire. Whether the etiology of this disorder is essentially central
      or peripheral is unclear; however, a presenting symptom may be persistent
      engorgement of genital erectile and vascular tissue. AIM: To describe a case of a
      distressed 27 year old pregnant woman with symptoms consistent with PGAD, and the
      intervention leading to the resolution of symptoms. METHODS: A patient with
      symptoms of PGAD was assessed. Information regarding this condition was offered.
      A manual therapy treatment was provided to decrease muscle hypertonus near the
      pudendal nerve, and a home intervention was suggested. RESULTS: Complete
      resolution of symptoms per patient's report 1 week later. CONCLUSION: Treatment
      with pelvic floor manual therapy directed at the pudendal nerve may provide safe
      and significant relief from PGAD symptoms in a pregnant woman patient.

PMID- 20059653
TI  - Long-term outcome of surgical treatment of penile fracture complicated by
      urethral rupture.
AB  - INTRODUCTION: The combination of lesions of the penile urethra and the corpus
      cavernosum is rare and is likely to worsen the immediate and long-term prognosis.
      AIM: To assess the late effects of penile fractures complicated by urethral
      rupture treated by immediate surgical intervention. METHODS: Fourteen patients
      with concomitant urethral rupture were treated surgically at our center. Those
      patients were seen in the outpatient follow-up clinic and were re-evaluated. MAIN
      OUTCOME MEASURES: Sexual Health Inventory for Men questionnaire, local
      examination, uroflowmetry and penile color Doppler ultrasound. RESULTS: The most
      common cause of penile fracture is sexual intercourse (50%). The site of tunical
      tear was in the proximal shaft of the penis in 3 patients (21%) and in the mid of
      the shaft in 11 patients (79%). Urethral injury was localized at the same level
      as the corpus cavernosum tear in all cases; and it was partial in 11 cases and
      complete in 3. Long-term follow-up (mean=90 months) was available for 12
      patients; among whom there was no complications in 4 (33%), painful erection in 1
      (8%), erectile dysfunction in 2 (17%), and palpable fibrous nodule in 5 (47%).
      All patients had a normal urinary flow except one who developed relative urethral
      narrowing that required regular dilatation for 1 month. CONCLUSIONS: The urethral
      injury complicating penile fracture is often partial and localized at the level
      of the corpora cavenosa tear. Standard treatment consists of immediate surgical
      repair of both urethral and corporal ruptures with no harmful long-term sequelae
      on urethral and erectile function in most of patients.

PMID- 20059654
TI  - A new perfusion model for studying erectile function.
AB  - INTRODUCTION: The present study introduces a newly devised in vitro penile
      perfusion model, which allows the measurement of changes in intracavernosum
      pressure (ICP), tension, and cyclic nucleotides in penile tissue in a one-step
      procedure. AIMS: We compared the penile perfusion model with the classical penile
      strip chamber model to develop the new model. METHODS: We investigated the role
      of nitric oxide-cyclic guanosine monophosphate pathway in both systems activated
      by acetylcholine or electrical field stimulation (EFS). We measured cGMP (cyclic
      guanosine monophosphate) in the penile corpus cavernosum smooth muscle in both
      systems and perfusates in the penile perfusion model. We determined ICP, tension,
      and cGMP simultaneously in penile perfusion model during the experiments. MAIN
      OUTCOME MEASURES: Changes of tension and cGMP in both models, and of cGMP in
      perfusates and of ICP in penile perfusion model. RESULTS: In both systems,
      acetylcholine relaxed the phenylephrine-precontracted penile corpus cavernosum
      smooth muscle in a concentration-dependent manner. EFS decreased the tension in
      both models and ICP in the penile perfusion model in a frequency-dependent
      manner. Pretreatment with atropine, Nomega nitro-L-arginine-methyl ester (L
      NAME), and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) blocked the
      acetylcholine-induced decrease in the tension in both models and ICP in penile
      perfusion model. Acetylcholine increased cGMP levels in the perfusate of penile
      perfusion model and the changes were attenuated by tetrodotoxin (TTX), atropine,
      L-NAME and ODQ. EFS increased cGMP levels of the penile corpus cavernosum smooth
      muscle of both models and the changes were attenuated by TTX, atropine, L-NAME,
      and ODQ. CONCLUSION: The results indicated that the responses of penile strip and
      perfused penile tissue to acetylcholine and EFS were very similar in both models
      in terms of tension and cGMP levels. Furthermore, the new model has more
      advantages over the classical penile strip chamber model in measuring
      intracavernosum metabolic changes and ICP without interruption of the procedure.

PMID- 20059655
TI  - PCOS and urethrovaginal space: 3-D volumetric and vascular analysis.
AB  - INTRODUCTION: The vaginal orgasm seems to be evocated by the stimulation of the G
      spot: a highly sensitive area on the anterior wall of the human vagina. However,
      the existence of such a spot is controversial. AIM: To evaluate, by the use of
      three-dimensional (3-D) ultrasonography, the anatomic structures of the
      urethrovaginal space both in polycystic ovarian syndrome (PCOS) patients and
      eumenorrheic non-hirsute controls. METHODS: Twenty-three (Group I) PCOS patients
      and 25 eumenorrheic young women (Group II) were submitted to two-dimensional (2
      D) and 3-D ultrasonography and color Doppler analysis of the urethrovaginal space
      and of the clitoris. MAIN OUTCOME MEASURES: 2-D ultrasonographic evaluation of
      the ovaries and of the urethrovaginal space; color Doppler evaluation of the
      ovarian stromal arteries, urethrovaginal main feeding artery, and dorsal clitoral
      arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power
      Doppler analysis of the vascularization index; flow index; and vascularization
      flow index; hormonal evaluation. RESULTS: The vaginal orgasm was present in 13/23
      (56%) patients in PCOS Group and in 13/25 (52%) in the controls. The 3-D
      reconstruction of the urethrovaginal space demonstrated a gland-like aspect with
      small feeding vessels: "female prostate." The 3-D mean volume of the "female
      prostate" was significantly higher in Group I (0.48 +/- 0.21 mL) than in Group II
      (0.39 +/- 0.19 mL; P = 0.044). The Virtual Organ Computer-aided AnaLys (VOCAL)
      built mean volume of the "female prostate" was positively correlated with the
      time since intercourse (r = 0.486; P = 0.032), with the total length of the
      urethrovaginal space (r = 0.616; P = 0.025) and with the testosterone (r = 0.424;
      P = 0.048) circulating values. CONCLUSIONS: The presence of the G-spot and its
      role in vaginal orgasm remains controversial. In Italians, and normal weight PCOS
      patients the hyperandrogenism seems to result in ovarian stromal and "female
      prostate" hyperplasia.

PMID- 20059656
TI  - 3-D volumetric and vascular analysis of the urethrovaginal space in young women
      with or without vaginal orgasm.
AB  - INTRODUCTION: The existence of the G-spot is controversial. AIM: To evaluate, by
      the use of three-dimensional (3-D) ultrasonography, the anatomic structures of
      the urethrovaginal space. METHODS: Nineteen (Group I) eumenorrheic young women
      who experienced, and 20 (Group II) who did not experience a vaginal orgasm
      underwent two-dimensional (2-D) and 3-D ultrasonography and color Doppler
      analysis of the urethrovaginal space and of the clitoris during the early
      follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: 2-D
      ultrasonographic evaluation of the urethrovaginal space, and color Doppler
      evaluation of the urethrovaginal main feeding artery and dorsal clitoral
      arteries; 3-D volume calculation of the urethrovaginal space, and 3-D power
      Doppler analysis of vascular indices of the urethrovaginal space and clitoral
      body (vascularization index, flow index, vascularization flow index); hormonal
      evaluation. RESULTS: The 3-D reconstruction of the urethrovaginal space
      demonstrated a gland-like aspect with small feeding vessels. The total length
      (19.1 + or - 2.7 mm vs. 17.5 + or - 2.1 mm; P = 0.047), measured with 2-D
      ultrasound, and the 3-D mean volume (0.59 + or - 0.13 mL vs. 0.26 + or - 0.07 mL;
      P < 0.001) of the structures contained in the urethrovaginal space were
      significantly higher in Group I than in Group II. The mean time since the last
      intercourse was 31 + or - 9 hours in Group I and 18 + or - 3 hours (P = 0.033) in
      Group II. The urethrovaginal space vascularization, the clitoral volume and
      vascularization, and the circulating hormonal values did not significantly differ
      among the two groups. The mean volume of the structures contained in the
      urethrovaginal space was correlated with time since intercourse (r = 0.685; P =
      0.021) and with serum testosterone (r = 0.637; P = 0.032) and androstenedione (r
      = 0.744; P = 0.011). CONCLUSIONS: The structures we observed in the
      urethrovaginal space have a gland-like aspect and their volume is correlated with
      both serum androgen concentrations and time since intercourse.

PMID- 20059657
TI  - Preoperative clinical and diagnostic characteristics of patients who require
      delayed IPP after primary Peyronies repair.
AB  - INTRODUCTION: Penile vascular abnormalities occur in a high proportion of
      patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and
      dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be
      used to help tailor individualized treatment for patients undergoing surgical
      intervention for their PD. However, precisely which parameters can be used to
      predict those patients with PD at risk for developing erectile dysfunction (ED)
      after intervention without inflatable penile prosthesis (IPP) has not been
      previously elucidated. AIM: To evaluate preoperative vascular parameters that
      predispose PD patients for developing ED after intervention without IPP. METHODS:
      Twenty-six patients receiving surgical intervention for their PD at a single
      center were retrospectively identified. Of these, 11 (42.3%) opted for primary
      repair without placement of an IPP. Three (27.2%) of these 11 patients went on to
      develop ED postoperatively. MAIN OUTCOME MEASURES: We compared various
      demographic, PDU, and DICC parameters between patients who did and did not fail
      primary repair of their PD. RESULTS: Mean age and follow-up of patients who went
      on to develop ED after repair of PD without IPP were not significantly different
      (P < 0.05). Resistive index (RI) and end diastolic volume were significantly
      different between these two groups (P < 0.05), while peak systolic volume, flow
      to maintain, and pressure decay were not significantly different. An RI cutoff of
      <0.80 was found to identify all patients who would later develop ED and fail
      primary repair without IPP. CONCLUSIONS: Penile vascular assessment can aid in
      counseling patients about their risk of developing delayed ED after primary
      repair of PD. In our cohort of patients, PDU provided preoperative risk
      stratification for postoperative erectile dysfunction in men undergoing
      Peyronie's repair without IPP. We propose the prospective study of an RI cutoff
      to identify patients at risk of failing primary PD repair without IPP.

PMID- 20059658
TI  - Characterization of VEGF and angiopoietins expression in human corpus cavernosum
      during aging.
AB  - INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is a highly prevalent and
      age-related disease, caused by endothelial dysfunction and impaired cavernous
      angiogenesis. However, cellular and molecular changes involved in erectile
      pathophysiology in aging male remain to be elucidated. AIM: To characterize the
      vascular organization, concomitantly with analysis of the expression of vascular
      endothelial growth factor (VEGF), Angiopoietin 1 (Ang1) and Angiopoietin 2 (Ang2)
      in young and aged human corpus cavernosum. METHODS: Human penile fragments were
      removed from patients submitted to penile deviation surgery (11 cases; 58-70
      years) and from potential organ donors (four cases; 18-28 years) without ED or
      risk factors for ED. Smooth muscle and connective tissue were assessed by
      Masson's trichrome staining and computer-assisted histomorphometry. Dual
      immunostaining for specific markers of endothelium (von Willebrand factor) and
      smooth muscle cell (alpha-actin), VEGF, Ang1 and Ang2 was assayed by fluorescence
      microscopy. Semi-quantification of expression of angiogenic factors was performed
      by Western blotting. MAIN OUTCOME MEASURES: Expression of VEGF and Angiopoietins
      in human corpus cavernosum, using a combination of histologic stainings, and
      molecular biology tools in order to achieve a better understanding of cavernosal
      tissue remodeling with aging. RESULTS: Aged human corpus cavernosum presented
      wider sinusoidal spaces, loss of muscle cell bundles, and increased connective
      tissue content. Ang1 was scarcely expressed in small clusters in smooth muscle
      cell cytoplasm with identical localization in both studied groups. VEGF
      expression was abundant in smooth muscle cell and its expression markedly
      decreased in aged tissue, contrasting with the expression of angiopoietins that
      increased in the aged corpus cavernosum. CONCLUSIONS: Immunoflourescent studies
      of cellular markers and growth factors help clarifying vascular organization and
      angiogenesis mechanisms in erectile tissue. Our findings demonstrate that the
      organization pattern of vascular endothelium and smooth muscle components of
      cavernosal tissue modifies during aging. Ang1 and Ang2 upregulation in human-aged
      penile tissue suggest a VEGF-independent vascular remodeling mechanism.

PMID- 20059659
TI  - Impact of nonorganic erectile dysfunction on spouses: a study from India.
AB  - INTRODUCTION: The overall outcome of men with erectile dysfunction (ED) depends a
      lot on participation in treatment of their partners/spouses. However,
      psychosexual functioning of partners/spouses has received scant attention. AIM:
      To study the psychosexual functioning of spouses of men with nonorganic ED in
      terms of their sexual satisfaction, psychological problems, marital adjustment,
      quality of life, and level of dysfunction. MAIN OUTCOME MEASURES: The main
      outcome measures for the partners of men with ED were symptom questionnaire,
      marital questionnaire (KDS-15 marital questionnaire), sexuality scale, quality of
      life enjoyment and satisfaction questionnaire, dyadic adjustment scale, and
      dysfunction analysis questionnaire. METHOD: Spouses of men with ED (n=50) and
      spouses of men without any psychosexual dysfunction (n=50) were compared for
      sexual and marital function, quality of life, and dyadic adjustment. The
      psychological impact was assessed by symptom questionnaire. RESULTS: Spouses of
      men with ED have significantly lower levels of marital and sexual satisfaction
      and higher levels of psychiatric symptoms than controls. Furthermore, the spouses
      of men with nonorganic ED also report poor quality of life in most domains of
      life and had higher level of dysfunction. CONCLUSION: Our findings support the
      Western data with regard to the psychosexual functioning of spouses/partners of
      men with ED and suggest that spouses/partners of men with ED should also be
      assessed thoroughly.

PMID- 20059660
TI  - Bulbocavernosus reflex to stimulation of prostatic urethra in patients with
      lifelong premature ejaculation.
AB  - INTRODUCTION: Lifelong premature ejaculation (LPE) is a prevalent sexual
      dysfunction among men, while its precise pathologic mechanisms have remained
      poorly understood. AIM: In our study, the correlation between excitability of
      bulbocavernosus reflex (BCR) to stimulation of the prostatic urethra and LPE was
      studied. METHODS: Twenty normal potent male volunteers and 42 patients with LPE
      were studied by inserting a specially designed Foley catheter with two electrodes
      mounted on its distal surface (intraurethral catheter electrode) into bladder to
      evoke the BCR to stimulation of prostatic urethra. Also, sensitivity of glans
      penis to electrical stimulation was detected by two surface electrodes. MAIN
      OUTCOME MEASURES: Sensory thresholds of BCR to stimulation of prostatic urethra,
      thresholds to evoke stable BCR, latencies of BCR, and sensory thresholds of glans
      penis to electrical stimulation. RESULTS: The mean sensory thresholds of BCR to
      stimulation of prostatic urethra, thresholds to evoke stable BCR, latencies of
      BCR, and sensory thresholds of glans penis were 12.38+/-3.71 mA (0.2 ms in
      duration, 1 Hz), 23.81+/-5.55 mA (0.2 ms, 1 Hz), 70.48+/-6.33 ms, and 11.89+/
      2.26 mA (0.04 ms in duration,3 Hz) in the patients with LPE, respectively, and
      were 18.20+/-2.68 mA (0.2 ms, 1 Hz), 34.76 +/- 4.15 mA (0.2 ms, 1 Hz), 71.20+/
      5.77 ms, and 14.16+/-1.94 mA (0.04 ms, 3 Hz) in the normal potent men,
      respectively (mean+/-SD). Statistically significant differences were seen
      regarding the sensory thresholds of BCR to stimulation of prostatic urethra, the
      thresholds to evoke stable BCR and the sensory thresholds of glans penis between
      the two groups (P<0.001). No statistically significant differences were seen
      regarding the latencies of BCR between the two groups (P>0.05). CONCLUSIONS:
      Patients with LPE might have hyperexcitable BCR to stimulation of prostatic
      urethra, which is probably one of the important factors for its etiology.

PMID- 20059661
TI  - Abortions and contraception use among Czech and Romanian women: comparison of
      representative national studies.
AB  - INTRODUCTION: This article presents the results of representative national
      studies comparing the behavior and attitudes of Czech and Romanian women
      regarding abortion and contraception use. AIM: Describe the attitudes to abortion
      and incidence of abortion in female population of these countries. METHODS:
      Independently and anonymously conducted questionnaire with 1,011 Czech and 1,001
      Romanian women, with the participants' age from 15 to 50 years. The sample
      represented both Czech and Romanian female populations with respect to age,
      education, and the size of their place of residence. MAIN OUTCOME MEASURES:
      Questionnaire studies awareness, attitudes, and behavior related to the area of
      sexual life, contraception, and family planning. RESULTS: Based on the acquired
      information, it can be postulated that Romanian women, despite having a less
      liberal opinion on abortions than their Czech peers, undergo abortion more often
      than Czech women (Romanian 28%, Czech 16%), are less informed about potential
      side effects, and more often use less reliable methods of contraception (the so
      called "natural contraception"-vs. hormonal contraception, which is the method of
      choice of Czech women). CONCLUSION: These results indicate that despite more
      liberal attitudes toward abortion, Czech women have less frequent incidence of
      abortion than Romanian women and they have more relevant information about
      contraception and their sexual behavior is more conscious and responsible.

PMID- 20059662
TI  - Utilization of pharmacotherapy for erectile dysfunction following treatment for
      prostate cancer.
AB  - INTRODUCTION: Pharmacotherapies improve sexual function following treatments for
      localized prostate cancer; however, patterns of care remain unknown. Aim. To
      ascertain post-treatment utilization of pharmacotherapies for erectile
      dysfunction (ED) using a population-based approach. METHODS: We identified 38,958
      men who underwent definitive treatment for localized prostate cancer during 2003
      2006 from the MarketScan Medstat data. MAIN OUTCOME MEASURES: We compared the use
      of ED pharmacotherapy at baseline (up to 3 months prior) and up to 30 months
      following radical prostatectomy (RP) or radiotherapy (RT) for localized prostate
      cancer by utilizing National Drug Classification codes for phosphodiesterase-5
      inhibitors (PDE5I), intracavernosal injectable therapies (IT), urethral
      suppositories and vacuum erection devices (VED). In adjusted analyses, we
      controlled for the effect of age, comorbidity, type of treatment, health plan and
      use of adjuvant hormone therapy on the use of pharmacotherapies. Results. Men
      undergoing RP vs. RT were younger with less co-morbid conditions. Utilization of
      PDE5I was up to three times greater for men undergoing RP vs. RT, 25.6% vs. 8.8%,
      (P < 0.0001) in the first post-treatment year, and usage of these agents was
      greatest for men undergoing minimally-invasive RP procedures. A higher percentage
      of men also used IT, suppositories and VED after RP vs. RT (P < 0.001). However,
      more men in the RT group received adjuvant hormonal therapy (39.53% vs. 5.25% for
      RP, P < 0.01). In adjusted analyses, men undergoing RP vs. RT were more than two
      times likely (OR 2.1, 95% CI 1.98, 2.26) to use PDE5I post-treatment while men on
      adjuvant hormonal therapy were less likely to use PDE5I (OR 0.74, 95% CI 0.70
      0.79, P < 0.0001). CONCLUSION: Men undergoing RP vs. RT, particularly minimally
      invasive RP, are more likely to employ IT, suppositories, VED, and PDE5I
      pharmacotherapy post-treatment.

PMID- 20059663
TI  - Pelvic floor muscle assessment outcomes in women with and without provoked
      vestibulodynia and the impact of a physical therapy program.
AB  - INTRODUCTION: Physical therapy (PT) may reduce the pain associated with provoked
      vestibulodynia (PVD) based on previous findings that pelvic floor muscle
      dysfunction (PFMD) is associated with PVD symptoms. AIMS: The goals of this study
      were: (i) to determine whether women with and without PVD differ on measures of
      pelvic floor muscle (PFM) behavior; and (ii) to assess the impact of PT treatment
      for women with PVD on these measures. METHODS: Eleven women with PVD and 11
      control women completed an assessment evaluating PFM behavior using surface
      electromyography (SEMG) recordings and a digital intravaginal assessment. Women
      with PVD repeated the assessment after they had undergone eight PT treatment
      sessions of manual therapy, biofeedback, electrical stimulation, dilator
      insertions, and home exercises. MAIN OUTCOME MEASURES: Superficial and deep PFM
      SEMG tonic activity and phasic activity in response to a painful pressure
      stimulus, PFM digital assessment variables (tone, flexibility, relaxation
      capacity, and strength). RESULTS: At pretreatment, women with PVD had higher
      tonic SEMG activity in their superficial PFMs compared with the control group,
      whereas no differences were found in the deep PFMs. Both groups demonstrated
      contractile responses to the painful pressure stimulus that were significantly
      higher in the superficial as compared with the deep PFMs, with the responses in
      the PVD group being higher than those in control women. Women with PVD had higher
      PFM tone, decreased PFM flexibility and lower PFM relaxation capacity compared
      with control women. Posttreatment improvements included less PFM responsiveness
      to pain, less PFM tone, improved vaginal flexibility, and improved PFM relaxation
      capacity, such that women with PVD no longer differed from controls on these
      measures. CONCLUSION: Women with PVD demonstrated altered PFM behavior when
      compared with controls, providing empirical evidence of PFMD, especially at the
      superficial layer. A PT rehabilitation program specifically targeting PFMD
      normalized PFM behavior in women with PVD.

PMID- 20059664
TI  - Genetic polymorphisms of 17 beta-hydroxysteroid dehydrogenase 3 and the risk of
      hypospadias.
AB  - INTRODUCTION: Hypospadias is a common congenital anomaly caused by incomplete
      fusion of urethral folds. Development of the urethra and external genital system
      in the male fetus is an androgen-dependent process. In this regard, enzymes 17
      beta-hydroxysteroid dehydrogenase type 3 (17 beta HSD3, encoded by HSD17B3) and
      steroid 5 alpha-reductase type 2 (encoded by SRD5A2) play crucial roles. AIM: To
      investigate the possible associations between common polymorphisms in HSD17B3 as
      well as well-known V89L polymorphism in SRD5A2 and risk of hypospadias. METHODS:
      A case-control study was performed between 1999 and 2005. There were 89 Japanese
      boys with hypospadias and 291 newborn controls. We genotyped HSD17B3-1999T>C,
      +10A>G, +20A>G, +139G>A (V31I), +913G>A (G289S), and SRD5A2+336G>C (V89L)
      polymorphisms by allelic discrimination assay. We measured mRNA expression of the
      wildtype G289 allele and the mutant S289 allele of the HSD17B3 gene in the
      transfected human fetal kidney HEK293 cells. MAIN OUTCOME MEASURES: Assessment of
      hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood
      samples: allele and genotype distribution of single nucleotide polymorphisms in
      these two genes in cases and controls. RESULTS: In our study, the risk of
      hypospadias was significantly higher in subjects carrying homozygous HSD17B3+913A
      (289S) alleles (odds ratio [OR]: 3.06; 95% confidence interval [CI]: 1.38-6.76).
      The risk of severe hypospadias was much higher in these subjects (OR: 3.93; 95%
      CI: 1.34-11.49). The mRNA expression levels of HSD17B3 G289 were higher than
      those of HSD17B3 S289 mutant (P < 0.001). In addition, the risk of severe
      hypospadias increased in boys carrying the SRD5A2+336C (89L) allele (OR: 3.19;
      95% CI: 1.09-9.36). CONCLUSIONS: These results suggest that the HSD17B3 G289S
      polymorphism may be a potential risk modifier for hypospadias. Our findings
      provide evidence that a certain genotype related to androgen production may
      potentiate risk of hypospadias.

PMID- 20059665
TI  - The relationship between anger and heterosexual behavior. An investigation in a
      nonclinical sample of urban Italian undergraduates.
AB  - INTRODUCTION: The relationship between anger and sexual behavior has never been
      thoroughly addressed, although it may deserve special attention because of its
      theoretical and practical consequences. AIM: We were interested in determining
      the extent in which trait anger was associated with dysfunctional sexual
      behavior, taking into account possible gender differences. METHOD: In this
      correlational study, 410 volunteers (199 men and 211 women) recruited from the
      students of the University of Messina, Italy, participated in the study. Median
      age of participants was 24 years. Men and women did not differ significantly in
      age (U = 18996, P = 0.606). MAIN OUTCOME MEASURES: The individuals' sexual
      behavior was assessed using the Sex and the Average Woman (or Man) questionnaire.
      RESULTS: We found no association between trait anger and either measure of sexual
      motivation: sexual excitement, r (396) = 0.11, P = 0.016, and sexual fulfillment,
      r (396) = -0.06, P = 0.134. Also, gender had no effect on either of these two
      variables. Trait anger had a positive significant correlation with neurotic sex,
      r (396) = 0.29, P < 0.002, impersonal sex, r (396) = 0.20, P < 0.002, and
      aggressive sex, r (396) = 0.28, P < 0.002. As we predicted, the associations
      between trait anger and these last three variables were stronger for men than for
      women (although only aggressive sex had a significant result). In multivariate
      analyses, impersonal sex ceased to be a significant correlate of trait anger.
      CONCLUSIONS: Trait anger has a negative effect on sexual behavior. It seems to
      exert its worst effects on the nature of sexual interpersonal behavior rather
      than on sexual motivation. We found no effect of gender on sexual motivation.
      However, the positive correlation between anger and relational sexual behavior
      was stronger for men than for women.

PMID- 20059666
TI  - Sexual quality of life of individuals with 46,XY disorders of sex development.
AB  - INTRODUCTION: There has recently been a growing acceptance that it is not only
      heterosexual functioning of surgically adjusted genitalia which should be
      considered when measuring the treatment outcome of persons with disorders of sex
      development (DSD) but also their overall sexual quality of life (SexQoL). AIM: A
      comprehensive cross-sectional investigation of SexQoL of persons with 46,XY DSD.
      METHODS: Forty-seven persons with 46,XY DSD (age 17-60 years) were examined by
      means of a questionnaire on various aspects of SexQoL. Scores were compared to a
      nonclinical convenience sample consisting of 145 women. Data were analyzed
      separately for diagnostic subgroups. Furthermore, persons whose external
      genitalia had been surgically corrected were compared with persons whose
      genitalia had been left unaltered. MAIN OUTCOME MEASURES: The Multidimensional
      Scale of Sexuality, the German Questionnaire on Feelings of Inadequacy in Social
      and Sexual Situations (FUSS), items on sexual dysfunctions according to DSM-IV-TR
      and self-constructed measures on sexual-activity history (e.g., previous sexual
      experience), sexual anxieties, and satisfaction with overall sex life and sexual
      function comprised the standardized assessment instruments. RESULTS: Compared
      with the nonclinical group, persons with 46,XY DSD had more often no partner (P =
      0.056), felt more insecure in social (Mdn(DSD) = 17.0, Mdn(comparison) = 12.0, P
      = 0.001) and sexual situations (Mdn(DSD) = 17.0, Mdn(comparison) = 11.0, P =
      0.006), had more sexual problems (Mdn(DSD) = 4.0, Mdn(comparison) = 3.0, P =
      0.001), and were less satisfied with overall sex life (Mdn(DSD) = 3.0,
      Mdn(comparison) = 4.0, P = 0.000) and sexual function (Mdn(DSD) = 4.0,
      Mdn(comparison) = 4.0, P = 0.000). Results were inconsistent with regard to
      sexual-activity history (e.g., previous sexual experience). Participants who
      underwent genital surgery showed less dyspareunia (P = 0.027) but more fear of
      injuries during intercourse (P = 0.019) than those whose genitals were left
      unaltered. CONCLUSIONS: SexQoL of persons with 46,XY DSD may be impaired.
      Differences in SexQoL between diagnostic subgroups, effect of corrective genital
      surgery, and the influence of gender assignment will have to be further
      investigated in future studies.

PMID- 20059667
TI  - Gene transfer of TRPC6 (dominant negative) restores erectile function in diabetic
      rats.
AB  - INTRODUCTION: Transient receptor potential (TRP) channels play an important role
      in modulating intracellular Ca(2+) ([Ca(2+)](i)) levels. AIM: We examined the
      hypothesis that overexpression of TRPC6(DN) (dominant negative) may contribute to
      decreased [Ca(2+)](i) levels in corporal smooth muscle (CSM). We also
      investigated whether gene transfer of TRPC6(DN) could restore erectile function
      in diabetic rats. METHODS: For the in vitro study, the K(Ca), K(ATP), and
      TRPC6(DN) channel genes were transferred using cDNA, into cultured human CSM
      cells and human embryonic kidney cells. For the in vivo study, young adult rats
      were divided into three groups: normal controls; diabetic controls transfected
      with vector only; and a diabetic group transfected with pcDNA of the TRPC6(DN)
      gene. MAIN OUTCOME MEASURES: After gene transfer, the effects of reducing
      [Ca(2+)](i) levels were assessed by Fura-2-based imaging analysis. The
      intracavernosal pressure (ICP) response to cavernosal nerve stimulation was
      assessed after intracorporal injection of TRPC6(DN) pcDNA. The transgene
      expression of the TRPC6(DN) was examined by reverse transcription polymerase
      chain reaction (RT-PCR) in rats transfected with TRPC6(DN) pcDNA. RESULTS: Gene
      transfer of ion channels effectively reduced [Ca(2+)](i). Among these channels,
      transfer of the TRPC6(DN) gene resulted in the greatest reduction of [Ca(2+)](i)
      in human CSM. The mean (+/-standard error of the mean) ratio of ICP to mean
      arterial pressure (BP) in the gene-transfer rats was 79.4 +/- 2.4% (N = 8). This
      was significantly higher than that in control rats (55.6 +/- 3.7% [N = 8]), and
      similar to that in the young control rats (83 +/- 2.2% [N = 12]). The RT-PCR
      showed expression of TRPC6(DN) genes in the transfected rats. CONCLUSION: Gene
      transfer of TRPC6(DN) not only reduced [Ca(2+)](i) in human CSM but also restored
      erectile function in diabetic rats. These results suggest that pcDNA transfer of
      TRPC6(DN) may represent a promising new form of therapy for the treatment of male
      erectile dysfunction in the future.

PMID- 20059668
TI  - Antithrombotic drugs in coronary artery disease: risk benefit ratio and bleeding.
AB  - The antithrombotic treatment of coronary artery disease is becoming increasingly
      complex. Aspirin is often combined with more potent antiplatelet agents such as
      thienopyridines and glycoprotein IIb/IIIa inhibitors. The classic anticoagulant
      unfractionated heparin is giving way to low-molecular-weight heparin, the
      pentasaccharide fondaparinux and the direct thrombin inhibitor bivalirudin.
      Warfarin (or another vitamin K antagonist) and antiplatelet agents are often
      required in combination for several months. Patients and physicians who have
      experienced major bleeding complications sometimes question the benefit of these
      treatment strategies. It is therefore crucial to try and weigh the impact on
      efficacy against safety. In this review the net benefit is discussed both
      numerically, comparing absolute reductions vs. increases in risks, and also by
      addressing the qualitative importance of each component in reaching the net
      benefit. Except for primary prophylaxis in patients at low-moderate risk for
      coronary events, there is a net benefit of antithrombotic therapy. With
      increasing severity of the coronary condition the net benefit generally prevails
      even with an increasing number of antithrombotic drugs combined. However, as the
      patient slowly stabilizes after appropriate interventions, it is necessary to de
      escalate the treatment in accordance with decreasing net benefit of prolonged
      combination therapy.

PMID- 20059669
TI  - A novel HBV recombinant (genotype I) similar to Vietnam/Laos in a primitive tribe
      in eastern India.
AB  - Genotyping of 20 strains of Hepatitis B virus (HBV) from the Idu Mishmi primitive
      tribe of northeast India identified multiple genotypes and the presence of a
      unique cluster grouping with strains from Vietnam and Laos identified as novel
      recombinants/genotype I. Sequence analysis (similarity and bootscan plots) of
      three complete HBV genomes from the tribe provided evidence of recombination.
      Phylogenetic analyses supported recombination between genotypes A, G and C. The
      Pre-S gene between nt 2943 and 397 was clearly of genotype A origin, whereas nt
      397-1397 represented genotype G and nt 1397-2943 represented genotype C.
      Percentage divergence from genotypes B, D, E, F, G and H varied from 9.2 +/-
      0.45% to 13.8 +/- 0.53%, whereas genotype A and C differed by 7.9 +/- 0.42% and
      7.4 +/- 0.39% respectively. The identification of similar recombinant viruses in
      three countries, especially in a primitive tribe with no contact with the outside
      world suggests that these viruses do not represent recent recombination events,
      but circulation of closely related viruses highly divergent from known HBV
      genotypes and should be classified as members of genotype 'I'.

PMID- 20059670
TI  - Lactobacilli prevent hydroxy radical production and inhibit Escherichia coli and
      Enterococcus growth in system mimicking colon fermentation.
AB  - AIMS: To explore the effect of Lactobacillus on redox state of colon chyme.
      METHODS AND RESULTS: Nine Lactobacillus strains were studied for the inhibition
      of lipid peroxide formation in Fe(2+)/ascorbate system and for their ability to
      chelate 'free' ferrous ion. The result shows both properties were strain specific
      and no relationship between them was found. Both properties of Lactobacillus
      paracasei Fn032, Lactobacillus rhamnosus GG (LGG) and Lactobacillus sp. Fn001
      were successively decreasing. LGG and Fn032 significantly decreased hydroxyl
      radicals (P < 0.01) in colonic fermentation model, in which considerable hydroxyl
      radicals occurred spontaneously. Addition of ferrous ion induced the production
      of hydroxyl radicals, which could be significantly inhibited by LGG, Fn032 (P <
      0.01) and Fn001 (P < 0.05). Ferrous ion significantly induced the growth of
      Enterococcus and Escherichia coli, which could be inhibited by all three
      Lactobacillus strains. Escherichia coli and Enterococcus show significantly
      positive correlation with hydroxyl radicals with R of 0.96 (P = 0.0002) and 0.91
      (P = 0.0017), respectively. CONCLUSIONS: Antioxidative Lactobacillus could
      modulate redox state in colonic fermentation system, which is related to their
      free radical-scavenging ability or antibacterial effect. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study proves that Lactobacillus strain could influence the
      redox state of gut chyme. Evaluation of antioxidative ability might be a powerful
      method for screening probiotic Lactobacillus strains.

PMID- 20059671
TI  - Progress of medical students after open admission or admission based on knowledge
      tests.
AB  - CONTEXT: Although admission to university in Austria is generally open for
      applicants who have successfully completed secondary school, in some areas of
      study, including human medicine and dentistry, the selection of students by
      additional criteria has become legally possible as a result of a decision by the
      European Court in 2005. We studied the impact of this important change on the
      temporal pattern of medical students' progress through the study programme.
      METHODS: All 2532 regular students admitted to the diploma programme in human
      medicine at the Medical University of Graz during the academic years 2002/03
      2007/08 were included in the analysis. Non-parametric and semi-parametric
      survival analysis techniques were employed to compare the time required to
      complete the first two study semesters (first part of the curriculum) before and
      after the implementation of admission tests. Temporal patterns of dropout before
      this goal was achieved were also investigated. Sex, age and nationality of
      students were assessed as potential confounding variables. RESULTS: The
      cumulative probability of study success was dramatically better in selected
      students versus those who were admitted openly (P < 0.0001). Whereas only 20.1
      26.4% of openly admitted students completed the first two study semesters within
      the scheduled time of 1 year, this percentage rose to 75.6-91.9% for those
      selected by admission tests. Similarly, the cumulative probability for dropping
      out of study was also significantly lower in selected students (P < 0.0001). By
      univariate as well as multivariate techniques, student nationality, age and sex
      were also identified as partly significant, albeit weak, predictors. DISCUSSION:
      The analysis convincingly demonstrates that, by contrast with open admission,
      performance-based selection of medical students significantly raises the
      probability of successful study progress. Additionally, the proportion of
      dropouts is significantly reduced. Thus, admission tests save considerable costs,
      in terms of both student time and public resources.

PMID- 20059672
TI  - Cross-institutional progress testing: feasibility and value to a new medical
      school.
AB  - OBJECTIVES: This study aimed to examine the feasibility of using a progress test
      to compare the rate of knowledge acquisition among students at a new medical
      school with that of students at a comparable but long-established school.
      METHODS: As part of an ongoing strategy, we administered the McMaster Personal
      Progress Index (PPI) on four occasions to the first two cohorts of students
      enrolled in the graduate-entry medical programme at the University of Limerick.
      We compared mean PPI scores for students at comparable stages in their courses at
      both schools. RESULTS: To date, the rate of knowledge acquisition is similar in
      students at both schools. CONCLUSIONS: Inter-institutional and international
      collaboration in progress testing is feasible and provides a useful quality
      assurance tool which can be used by new schools to reassure students, faculty
      members and accrediting bodies.

PMID- 20059673
TI  - A new conception of knowledge, a new conception of learning: from Tetris to
      Rubik's cube.

PMID- 20059674
TI  - Relationship between clinical assessment and examination scores in determining
      clerkship grade.
AB  - CONTEXT: Grades in clinical clerkships are typically based on a combination of
      clinical assessments from teachers, as well as results of more reliable (but
      perhaps less valid) scores on standardised tests of knowledge. It is not clear
      how these scores are combined in practice to yield a final summative grade.
      METHODS: Our subjects were 83 students who rotated through five clinical
      clerkships during a single year. After computing univariate correlations between
      clinical assessment scores and standardised examination scores, we performed
      logistic regression analyses for each clerkship to predict the final grade from
      these two variables. We compared actual grade with predicted grade under various
      hypothetical policies for combining these two variables. Finally, we assessed
      whether some students would systematically benefit from these policies. RESULTS:
      Clerkships varied in their univariate correlations between scores on clinical
      assessments and scores on standardised examinations. Clerkships with the lowest
      correlations tended to give more weight to standardised examination scores.
      Grading committees adjusted a substantial minority of grades to account for
      factors that were not reflected in either score. There did not appear to be a
      systematic bias in grading committee effect across the five clerkships.
      CONCLUSIONS: These results suggest a number of testable hypotheses about the
      cognitive processes by which evaluators combine various pieces of information to
      yield a summative performance score.

PMID- 20059675
TI  - Medical students' views of power in doctor-patient interactions: the value of
      teacher-learner relationships.
AB  - CONTEXT: This paper aims to contribute to the important, and relatively
      underexplored, area of medical education research that seeks to illuminate the
      value and meaning of relationships in the undergraduate education of doctors.
      Here I present new empirical material in which I ground my reflections on some
      ways in which teacher-learner relationships can help address medical students'
      often uncritical views of professional practice. The views I illustrate are of
      particular significance as they contrast sharply with the participative models of
      practice promoted by current policy, professional and educational discourses.
      METHODS: My reflections stem from the analysis of data I generated for a larger,
      broadly ethnographic study exploring students' approaches to their future role as
      practitioners in one UK medical school. I draw upon this larger body of data and
      focus here on two examples in particular of the more general uncritical readings
      of medical professionalism I encountered at Sundown Medical School (an invented
      name), namely: students' often reductive views of medical power, and their
      simplistic formulations of patient education. DISCUSSION: I argue for the need to
      foster richer and more critical understandings of professional power and
      knowledge among students and educators, and suggest here that teacher-learner
      interactions could have an important role in fostering such richer
      understandings. I argue that teacher-learner relationships can model some of the
      dynamics of the practitioner-patient interaction and thus provide useful
      opportunities for closer and more critical analysis of power, education and
      knowledge in the medical school classroom as well as in the consultation room.
      CONCLUSIONS: I suggest that effective integration of participative and critical
      pedagogical strategies in medical curricula and more structured involvement of
      patients in the role of teachers may represent valuable strategies for the
      development of learning relationships that better promote reflexive and
      collaborative forms of professionalism.

PMID- 20059676
TI  - Does patient feedback improve the consultation skills of general practice
      trainees? A controlled trial.
AB  - CONTEXT: This study aimed to assess if an additional patient feedback training
      programme leads to better consultation skills in general practice trainees (GPTs)
      than regular communication skills training, and whether process measurements
      (intensity of participation in the programme) predict the effect of the
      intervention. METHODS: We carried out a controlled trial in which two sub-cohorts
      of GPTs were allocated to an intervention group (n = 23) or a control group (n =
      30), respectively. In 2006, allocated first-year GPTs in the VU University
      Medical Centre attended a patient feedback training programme in addition to the
      regular communication skills training. The control group attended only regular
      communication skills training. Trainees were assessed by simulated patients who
      visited the practices and videotaped the consultations at baseline and after 3
      months. The videotapes were randomly assigned to eight trained staff members. The
      MAAS-Global Instrument (range 0-6) was used to assess (a change in) trainee
      consultation skills. RESULTS: were analysed using a multi-level, linear mixed
      model analysis. Results Data on 50 GPTs were available for the follow-up
      analysis. Both intervention group and control group GPTs improved their
      consultation skills: mean MAAS-Global scores for all participants were 3.29
      (standard deviation [SD] 0.75) at baseline and 3.54 (SD 0.66) at follow-up (P =
      0.047). The improvement in MAAS-Global scores in the intervention group did not
      differ significantly from the improvement in the control group. The analysis
      showed a trend for intensity of participation in the patient feedback programme
      to predict greater improvement in MAAS-Global scores. DISCUSSION: Although the
      baseline scores were already in the high range, consultation skills in both
      groups improved significantly. This is reassuring for current teaching methods.
      The patient feedback programme did not improve consultation skills more than
      regular communication skills training. However, a subgroup of GPTs who
      participated intensively in the programme did improve their consultation skills
      further in comparison with the less motivated subgroup.

PMID- 20059677
TI  - User perceptions of multi-source feedback tools for junior doctors.
AB  - CONTEXT: The effectiveness of multi-source feedback (MSF) tools, which are
      increasingly important in medical careers, will be influenced by their users'
      attitudes. This study compared perceptions of two tools for giving MSF to UK
      junior doctors, of which one provides mainly textual feedback and one provides
      mainly numerical feedback. We then compared the perceptions of three groups,
      including: trainees; raters giving feedback, and supervisors delivering feedback.
      METHODS: Postal questionnaires about the usability, usefulness and validity of a
      feedback system were distributed to trainees, raters and supervisors across the
      north of England. RESULTS: Questionnaire responses were analysed to compare
      opinions of the two tools and among the different user groups. Overall there were
      few differences. Attitudes towards MSF in principle were positive and the tools
      were felt to be usable, but there was little agreement that they could
      effectively identify doctors in difficulty or provide developmental feedback. The
      text-oriented tool was rated as more useful for giving feedback on communication
      and attitude, and as more useful for identifying a doctor in difficulty. Raters
      were more positive than other users about the usefulness of numerical feedback,
      but, overall, text was felt to be more useful. Some trainees expressed concern
      that feedback was based on insufficient knowledge of their work. This was not
      supported by raters' responses, although many did use indirect information.
      Trainees selected raters mainly for the perceived value of their feedback, but
      also based on personal relationships and the simple pragmatics of getting a tool
      completed. DISCUSSION: Despite positive attitudes to MSF, the perceived
      effectiveness of the tools was low. There are small but significant preferences
      for textual feedback, although raters may prefer numerical scales. Concerns about
      validity imply that greater awareness of contextual and psychological influences
      on feedback generation is necessary to allow the formative benefits of MSF to be
      optimised and to negate the risk of misuse in high-stakes contexts.

PMID- 20059678
TI  - Comparing the academic performance of graduate- and undergraduate-entry medical
      students.
AB  - OBJECTIVE: This study compared the academic performance of graduate- and
      undergraduate-entry medical students completing the same pre-clinical curriculum
      and assessment at a large metropolitan university. Arguments have been made for
      the relative merits of both graduate- and undergraduate-entry medical programmes.
      However, data on the academic performance of graduate and undergraduate entrants
      are relatively scarce. METHODS: This retrospective study adopted a quasi
      experimental design to compare data from assessments of bioscience knowledge and
      clinical skills undertaken across 2 years for four cohorts of medical students
      (who commenced their studies between 2002 and 2005). Percentage final results for
      four bioscience knowledge subjects and four clinical skills assessments (based on
      objective structured clinical examination [OSCE] results) were compared for 240
      graduates and 464 undergraduates using multivariate analysis of variance
      (manova). RESULTS: Graduate-entry students performed marginally better than
      undergraduate-entry students on all four bioscience knowledge assessments
      (partial eta-squared [n(p)(2)], n(p)(2)=0.04) and also on early clinical skills
      assessments (n(p)(2)=0.06). CONCLUSIONS: Graduate-entry students had a marginal
      academic performance advantage during the early years of this medical course.
      Most graduate-entry students had a first degree in a science discipline; thus
      their advantage may be explained by prior bioscience knowledge. Their performance
      advantage in clinical skills is less easily attributed to prior learning.
      Instead, this result provides some evidence for a possible advantage related to
      age. The marginal differences in early academic and clinical performance probably
      suggest that both graduate and undergraduate entry should exist in parallel to
      preserve multiple points of entry to the medical profession.

PMID- 20059679
TI  - Regulation of morphological differentiation in S. coelicolor by RNase III (AbsB)
      cleavage of mRNA encoding the AdpA transcription factor.
AB  - RNase III family enzymes, which are perhaps the most widely conserved of all
      ribonucleases, are known primarily for their role in the processing and
      maturation of small RNAs. The RNase III gene of Streptomyces coelicolor, which
      was discovered initially as a global regulator of antibiotic production in this
      developmentally complex bacterial species and named absB (antibiotic biosynthesis
      gene B), has subsequently also been found to modulate the cellular abundance of
      multiple messenger RNAs implicated in morphological differentiation. We report
      here that regulation of differentiation-related mRNAs by the S. coelicolor
      AbsB/RNase III enzyme occurs largely by ribonucleolytic cleavage of transcripts
      encoding the pleiotropic transcription factor, AdpA, and that AdpA and AbsB
      participate in a novel feedback-control loop that reciprocally regulates the
      cellular levels of both proteins. Our results reveal a previously unsuspected
      mechanism for global ribonuclease-mediated control of gene expression in
      streptomycetes.

PMID- 20059681
TI  - Structural studies on the full-length LysR-type regulator TsaR from Comamonas
      testosteroni T-2 reveal a novel open conformation of the tetrameric LTTR fold.
AB  - LysR-type transcriptional regulators (LTTRs) constitute the largest family of
      regulators in prokaryotes. The full-length structures of the LTTR TsaR from
      Comamonas testosteroni T-2 and its complex with the natural inducer para
      toluensulfonate have been characterized by X-ray diffraction. Both ligand-free
      and complexed forms reveal a dramatically different quaternary structure from
      that of CbnR from Ralstonia eutropha, or a putative LysR-type regulator from
      Pseudomonas aeruginosa, the only other determined full-length structures of
      tetrameric LTTRs. Although all three show a head-to-head tetrameric ring, TsaR
      displays an open conformation, whereas CbnR and PA01-PR present additional
      contacts in opposing C-terminal domains that close the ring. Such large
      differences may be due to a broader structural versatility than previously
      assumed or either, reflect the intrinsic flexibility of tetrameric LTTRs. On the
      grounds of the sliding dimer hypothesis of LTTR activation, we propose a
      structural model in which the closed structures could reflect the conformation of
      a ligand-free LTTR, whereas inducer binding would bring about local changes to
      disrupt the interface linking the two compact C-terminal domains. This could lead
      to a TsaR-like, open structure, where the pairs of recognition helices are closer
      to each other by more than 10 A.

PMID- 20059696
TI  - Necrotising external otitis caused by Aspergillus wentii: a case report.
AB  - Necrotising external otitis (NEO) is a destructive, potentially fatal, infection
      usually seen in elderly diabetics or the immunocompromised. The commonest
      causative organism is Pseudomonas but immunocompromised patients are additionally
      susceptible to opportunistic infections. Here we describe the first reported case
      of NEO caused by a previously unknown human pathogen--Aspergillus wentii. A
      review of the literature reveals that fungal NEO is associated with a high rate
      of cranial nerve palsies suggesting that infections are not being treated rapidly
      enough to prevent morbidity. Fungal infection should be considered early in
      immunocompromised patients and microbiological diagnosis should be obtained
      wherever possible.

PMID- 20059697
TI  - NK-1 receptor is involved in the decreased movement in a rat chronic acid reflux
      oesophagitis model.
AB  - BACKGROUND: We previously reported that rats with reflux oesophagitis (RE) show a
      decrease in voluntary movement, which could be used as a measure of chronic
      visceral symptoms. However, what mediates these symptoms is still unknown, and
      pain-related neuropeptides or their receptors in oesophageal mucosa are possibly
      related to the symptom generation of oesophagitis. In the present study, we
      investigated the role of NK-1 receptor (NK-1R) as a mediator of oesophagitis
      symptoms. METHODS: Chronic RE was surgically induced using rats. The degree or
      severity of oesophageal symptoms was evaluated by assessing voluntary movement,
      which was monitored using an infrared sensor system. The NK-1R antagonist, L
      732,138, was administered and changes in voluntary movement were assessed. Ten
      days after surgery, the rats were killed to examine the oesophagus. NK-1R and
      tachykinin-1 mRNA were detected by real-time RT-PCR. NK-1R protein expression was
      examined by Western blotting. KEY RESULTS: Voluntary movement of the oesophagitis
      model rats was significantly lower than that of the sham-operated rats on day 10.
      The size of oesophageal mucosal erosion did not correlate with the amount of
      voluntary movement. The amount of NK-1R protein and mRNA in the oesophageal
      tissue was significantly higher at both the erosion and non-erosion sites. The
      amount of tachykinin-1 mRNA in oesophageal tissue at the non-erosion sites was
      significantly higher in oesophagitis rats. The voluntary movement of oesophagitis
      rats was significantly increased by the administration of L-732,138. CONCLUSIONS
      & INFERENCES: The NK-1R and related neuropeptides are possibly involved in the
      decrease in voluntary movement of RE.

PMID- 20059698
TI  - Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride
      (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal
      dosage.
AB  - BACKGROUND: Acotiamide is a selective acetylcholinesterase inhibitor and enhances
      the actions of cholinergic neurons localized in the stomach. METHODS: The present
      two studies were conducted to examine the optimal dosage of acotiamide
      hydrochloride (Z-338) in patients with functional dyspepsia (FD) in Japan. KEY
      RESULTS: The improvement rate of 'subjects global assessment of overall treatment
      efficacy (OTE)' at the final evaluation was approximately 10% higher in the
      acotiamide 100 mg group than that in the placebo group with good reproducibility
      though there was no significant differences at primary endpoint. The elimination
      rate of postprandial fullness in the acotiamide 100 mg group was significantly
      higher compared to placebo group. In addition, the post hoc analysis showed that
      in patients whose main complaints are meal-related symptoms such as postprandial
      fullness, upper abdominal bloating and/or early satiety, the improvement rate of
      'OTE' at final evaluation in acotiamide 100 mg group was significantly superior
      to that in the placebo group. CONCLUSIONS & INFERENCES: These results suggest
      that acotiamide possesses efficacy on FD and more specifically its meal-related
      symptoms of FD.

PMID- 20059699
TI  - ICC-MY coordinate smooth muscle electrical and mechanical activity in the murine
      small intestine.
AB  - BACKGROUND: Animals carrying genetic mutations have provided powerful insights
      into the role of interstitial cells of Cajal (ICC) in motility. One classic model
      is the W/W(V) mouse which carries loss-of-function mutations in c-kit alleles,
      but retains minimal function of the tyrosine kinase. Previous studies have
      documented loss of slow waves and aberrant motility in the small intestine of
      W/W(V) mice where myenteric ICC (ICC-MY) are significantly depleted. METHODS:
      Here, we used morphological and electrophysiological techniques to further assess
      the loss of ICC around the circumference of the small intestine and determine
      consequences of losing ICC-MY on electrical activity, Ca(2+) transients and
      contractions of the longitudinal muscle (LM). KEY RESULTS: In wild-type mice,
      there was coherent propagation of Ca(2+) transients through the ICC-MY network
      and spread of this activity to the LM. In short segments of small intestine in
      vitro and in exteriorized segments, slow waves coordinated smoothly propagating
      Ca(2+) waves and contractions in the LM of wild-type mice. In W/W(V) mice, Ca(2+)
      waves were initiated at variable sites along and around intestinal segments and
      propagated without constraint unless they collided with other Ca(2+) waves. This
      activity resulted in abrupt, uncoordinated contractions. CONCLUSIONS &
      INFERENCES: These results show how dominance of pacemaking by ICC-MY coordinates
      propagating con-tractions and regulates the spontaneous activity of smooth
      muscle.

PMID- 20059700
TI  - Riser's reflux--an eye-opening experience.
AB  - BACKGROUND: Patients with gastro-oesophageal reflux disease (GORD) commonly
      report waking up in the morning with a sour or bitter taste in their mouth. The
      aim of the study was to compare the prevalence and frequency of acid reflux
      events prior to and immediately after awakening from sleep in the morning between
      GORD patients and normal subjects. METHODS: Thirty-nine patients with heartburn
      at least three times a week and abnormal pH test and nine healthy controls were
      included. All subjects were evaluated by demographic and GORD Symptom Checklist
      questionnaires. Subjects underwent pH testing concomitantly with actigraphy. A
      novel technology that simultaneously integrates raw actigraphy and pH monitoring
      data was utilized to determine the presence, frequency, and characteristics of
      acid reflux events prior to (up to 1 h) and immediately after (10 and 20 min)
      awakening from sleep in the morning. KEY RESULTS: Nineteen (48.7%) of the GORD
      patients had an acid reflux event within the first 20 min after awakening from
      sleep in the morning as compared to only seven (17.9%) during the hour prior to
      awakening. Within the first 10 and 20 min after awakening, patients had a total
      of 32 and 60 acid reflux events, respectively, as compared to 14 during the 1 h
      prior to awakening (P < 0.05). None of the healthy control patients demonstrated
      any reflux events during these three studied periods (P < 0.001). CONCLUSIONS &
      INFERENCES: Riser's reflux is very common among GORD patients and possibly may
      explain reports of early-morning GORD symptoms.

PMID- 20059701
TI  - Review: cell cycle aberrations and neurodegeneration.
AB  - The cell cycle is a highly regulated and fundamental cellular process that
      involves complex feedback regulation of many proteins, and any compromise to its
      integrity elicits dire consequences for the cell. For example, in
      neurodegenerative diseases such as Alzheimer disease (AD), evidence for abnormal
      cell cycle re-entry precedes other hallmarks of disease and as such, implicates
      cell cycle aberrations in the aetiology of AD. The mechanism(s) for cell cycle re
      entry in AD, however, remain unclear. Current theory suggests it to be part of a
      combination of early events that together elicit the degenerative pathology and
      cognitive phenotype consistent with the disease. We propose a 'Two-Hit
      Hypothesis' that highlights the concerted interaction between cell cycle
      alterations and oxidative stress that combine to produce neurodegeneration. Here,
      we review the evidence implicating cell cycle mechanisms in AD and how such
      changes, especially in combination with oxidative stress, would lead to a cascade
      of events leading to disease. Based on this concept, we propose new opportunities
      for disease treatment.

PMID- 20059702
TI  - Presence of three mycorrhizal genes in the common ancestor of land plants
      suggests a key role of mycorrhizas in the colonization of land by plants.
AB  - *The colonization of land by plants fundamentally altered environmental
      conditions on earth. Plant-mycorrhizal fungus symbiosis likely played a key role
      in this process by assisting plants to absorb water and nutrients from soil.
      *Here, in a diverse set of land plants, we investigated the evolutionary
      histories and functional conservation of three genes required for mycorrhiza
      formation in legumes and rice (Oryza sativa), DMI1, DMI3 and IPD3. *The genes
      were isolated from nearly all major plant lineages. Phylogenetic analyses showed
      that they had been vertically inherited since the origin of land plants. Further,
      cross-species mutant rescue experiments demonstrated that DMI3 genes from
      liverworts and hornworts could rescue Medicago truncatula dmi3 mutants for
      mycorrhiza formation. Yeast two-hybrid assays also showed that bryophyte DMI3
      proteins could bind to downstream-acting M. trunculata IPD3 protein. Finally,
      molecular evolutionary analyses revealed that these genes were under purifying
      selection for maintenance of their ancestral functions in all mycorrhizal plant
      lineages. *These results indicate that the mycorrhizal genes were present in the
      common ancestor of land plants, and that their functions were largely conserved
      during land plant evolution. The evidence presented here strongly suggests that
      plant-mycorrhizal fungus symbiosis was one of the key processes that contributed
      to the origin of land flora.

PMID- 20059703
TI  - Direct medical cost of overweight and obesity in the USA: a quantitative
      systematic review.
AB  - To estimate per-person and aggregate direct medical costs of overweight and
      obesity and to examine the effect of study design factors. PubMed (1968-2009),
      EconLit (1969-2009) and Business Source Premier (1995-2009) were searched for
      original studies. Results were standardized to compute the incremental cost per
      overweight person and per obese person, and to compute the national aggregate
      cost. A total of 33 US studies met review criteria. Among the four highest
      quality studies, the 2008 per-person direct medical cost of overweight was $266
      and of obesity was $1723. The aggregate national cost of overweight and obesity
      combined was $113.9 billion. Study design factors that affected cost estimates
      included use of national samples vs. more selected populations, age groups
      examined, inclusion of all medical costs vs. obesity-related costs only, and body
      mass index cut-offs for defining overweight and obesity. Depending on the source
      of total national healthcare expenditures used, the direct medical cost of
      overweight and obesity combined is approximately 5.0% to 10% of US healthcare
      spending. Future studies should include nationally representative samples,
      evaluate adults of all ages, report all medical costs and use standard body mass
      index cut-offs.

PMID- 20059704
TI  - Accuracy of simple clinical and epidemiological definitions of childhood obesity:
      systematic review and evidence appraisal.
AB  - The optimum means of defining obesity in children is unclear, creating variation
      in practice, and hindering obesity surveillance, prevention and treatment. This
      study aimed to review evidence on the use of body mass index (BMI) and waist
      circumference for diagnosis of high body fat content and adverse cardiometabolic
      risk factors in children and adolescents. A systematic literature review was
      carried out and evidence appraised using the Quality Assessment of Studies of
      Diagnostic Accuracy in Systematic Reviews method. Literature searching began
      following the last systematic review of this topic (end 2001) and collected
      evidence in MEDLINE and EMBASE in 0- to 18-year-olds that compared the accuracy
      of BMI vs. waist circumference and compared BMI interpreted relative to national
      reference data vs. BMI interpreted relative to Cole/International Obesity Task
      Force international reference data. Ten studies compared diagnostic accuracy of
      BMI vs. waist circumference: they reported no improved identification of adverse
      cardiometabolic risk profiles from waist circumference over that provided by high
      BMI. Eight studies compared BMI with national reference data vs. the
      international approach: 5/8 found significantly poorer accuracy (lower
      sensitivity) using BMI with the international approach; 3/8 found similar
      sensitivity; in 7/7 studies that compared specificity this was similar. In
      conclusion, the present review provides no compelling evidence for use of either
      high waist circumference or BMI interpreted using the International Obesity Task
      Force approach in preference to the use of national BMI percentiles for the
      identification of children and adolescents with excess fatness and adverse
      cardiometabolic risk profile.

PMID- 20059705
TI  - Selection of priority groups for obesity prevention: current approaches and
      development of an evidence-informed framework.
AB  - Resources for obesity prevention interventions are inevitably limited,
      necessitating the selection of priority groups to ensure effective and equitable
      use of funds. This paper aims to review published approaches to selection of
      priority groups ('target populations') for obesity prevention, and to present the
      development of a new systematic framework for organizing and assessing evidence
      for selecting priority groups. A review was conducted of the process and
      justification described for selecting priority groups in a sample of obesity
      prevention publications. Using the results of this review and adaptation of
      theory and frameworks in both the obesity prevention and health promotion
      priority-setting literature, a framework was developed for assessment of
      potential priority groups for obesity prevention. The published literature lacks
      discussion of and explicit processes for selection of priority groups for obesity
      prevention intervention. The new framework describes specific types of evidence
      that should be considered in the assessment of a potential priority group for
      obesity prevention and has applications for funding and implementing community
      based or settings-level obesity prevention interventions and research.
      Application of this framework has the potential to enhance the effective use of
      limited obesity prevention resources and to identify areas in need of additional
      research evidence.

PMID- 20059706
TI  - Adipokines and dietary interventions in human obesity.
AB  - Obesity is a multisystem disorder associated with cardiovascular and metabolic
      complications. According to recent studies, it is characterized as a condition of
      low-grade inflammation with altered adipose tissue function and secretion of
      various adipokines. One of the strategies in obesity treatment is dietary
      intervention (DI) that could modulate cytokine levels in a favourable way. The
      aim of this review was to summarize the results of studies performed in the last
      13 years investigating DI programmes accompanied with weight loss in relation to
      profile of adipokines at different level (adipose tissue mRNA, adipose tissue
      secretion and circulating level) and identify whether modulations of adipokines
      are implicated in the positive effects of DIs. The overall finding is that DIs
      leading to 5-10% weight loss modulate production of certain adipokines and
      generally induce improvement of clinical parameters, e.g. insulin sensitivity,
      but the amelioration of obesity complications is not coherent with the pattern of
      adipokine regulation, except maybe for leptin. Global analysis of the adipose
      tissue secretome and measurement of panels of adipokines may prove more
      informative than studies on individual molecules.

PMID- 20059707
TI  - Obesity and mobility disability in the older adult.
AB  - Mobility disability is becoming prevalent in the obese older population (> or =
      60 years of age). We included a total of 13 cross-sectional and 15 longitudinal
      studies based on actual physical assessments of mobility in the obese older
      population in this review. We systematically examined existing evidence of which
      adiposity estimate best predicted mobility disability. Cross-sectional studies
      (82-4000 participants) showed poorer lower extremity mobility with increasing
      obesity severity in both men and women. All longitudinal studies (1-22 years)
      except for one, reported relationships between adiposity and declining mobility.
      While different physical tests made interpretation challenging, a consistent
      finding was that walking, stair climbing and chair rise ability were compromised
      with obesity, especially if the body mass index (BMI) exceeded 35 kg m(-2). More
      studies found that obese women were at an increased risk for mobility impairment
      than men. Existing evidence suggests that BMI and waist circumference are
      emerging as the more consistent predictors of the onset or worsening of mobility
      disability. Limited interventional evidence shows that weight loss is related
      with increased mobility and lower extremity function. Additional longitudinal
      studies are warranted that address overall body composition fat and muscle mass
      or change on future disability.

PMID- 20059708
TI  - Dietary and lifestyle interventions for weight management in adults from minority
      ethnic/non-White groups: a systematic review.
AB  - Minority ethnic/non-White populations are more prone to weight gain and more
      susceptible to obesity-related complications. The objective of this study was to
      systematically review dietary and lifestyle interventions for weight management
      in minority ethnic groups. Electronic databases and reference lists of original
      studies and reviews were searched for studies on dietary and lifestyle weight
      management interventions published. Randomized clinical trials with >=6-month
      duration were included. Nineteen studies met the inclusion criteria. Fourteen
      studies involved African-Americans, one in non-White Hispanics, one in Japanese
      Americans and three in both African-Americans and non-White Hispanics. Most of
      the interventions proved relatively effective. However, significant drawbacks
      were noted for several of these studies, such as small sample size, high
      attrition rates and lack of follow-up data. Better quality and long-term trials
      are required in order to investigate in detail the effectiveness of lifestyle
      changes for weight management in these populations and eventually support
      evidence-based recommendations.

PMID- 20059709
TI  - Cardiac anatomy for the interventional arrhythmologist: I.terminology and
      fluoroscopic projections.
AB  - Cardiac anatomy is complex and its understanding is essential for the
      interventional arrhythmologist. The first difficulty is the terminology used to
      describe the location of sites of mapping and ablation. For many years,
      electrophysiologists have named these positions following the conventional
      electrocardiographical vocabulary, or the terminology used by surgeons performing
      arrhythmic surgery. This traditional nomenclature, however, failed to take note
      of the crucial principle of considering the location of the heart in the human
      body as viewed in its erect position. In other words, it had failed to use an
      attitudinally appropriate terminology. Almost 10 years ago, a new attitudinal
      nomenclature was proposed for the right and left atrioventricular junctions. In
      this first of a series of reviews of cardiac anatomy as seen by the
      interventional arrhythmologist, we discuss the role of attitudinally appropriate
      terminology, and relate this to the projections used for cardiac fluoroscopy,
      fluorography, and angiography. Throughout our series of reviews, we will
      illustrate the value of The Visible Human Slice and Surface Server in
      facilitating the understanding of the fluoroscopic anatomy. (PACE 2010; 497-507).

PMID- 20059710
TI  - Pre-ICD illness beliefs affect postimplant perceptions of control and patient
      quality of life.
AB  - BACKGROUND: The implantable cardioverter defibrillator (ICD) is a device used in
      the treatment of ventricular arrhythmias and the prevention of sudden cardiac
      death. However, the ICD has been associated with negative psychological outcomes
      such as anxiety, depression, panic, and poor quality of life (QoL). Recent
      studies suggest that the preimplantation psychology of patients, combined with
      their postimplantation perceptions about their cardiac condition, are greater
      contributory factors than their medical status to a poor outcome. METHOD: Our
      study employed an interview-based qualitative grounded theory methodology to
      explore whether medical history hetereogeneity and illness beliefs impact on the
      QoL of 13 ICD patients. RESULTS: Perceived control emerged as the core category
      related to QoL with three subsystem themes related to control: (1) illness
      beliefs, attributions, and appraisals; (2) coping resources and strategies; and
      (3) the social world. Patients at risk for the poorest adaptation were younger
      (<45), unemployed, and with an acute onset cardiac history. These patients
      interpreted their illness as severe, utilized emotion-focused coping (e.g.,
      avoidance of situations), and believed themselves to be socially excluded.
      Adjusted patients used proactive problem-focused coping (e.g., normalizing) and
      minimized consequences of the device. CONCLUSIONS: The data developed a
      theoretical model of QoL, which identified perceived control, illness beliefs,
      and coping impacting on adjustment. From our study, we have a wider understanding
      of the combination psychological issues relevant to ICD patients and are able to
      treat those at risk with interventions to promote adjustment in the context of a
      society that values health and well-being.

PMID- 20059711
TI  - The relationship between warfarin, aspirin, and clopidogrel continuation in the
      peri-procedural period and the incidence of hematoma formation after device
      implantation.
AB  - BACKGROUND: Many patients requiring permanent pacemaker (PPM) or implantable
      cardiac defibrillator (ICD) placement are anticoagulated with warfarin, aspirin
      (ASA), and clopidogrel for a number of thromboembolic risk indications. The
      present review sought to evaluate the relationship between continuation of these
      medications in the peri-procedural period and the incidence of hematoma formation
      after implantation. METHODS: We retrospectively reviewed consecutive patients
      undergoing PPM and ICD implantation at our hospital from January 2007-2009. All
      patients on warfarin, aspirin, and clopidogrel were maintained on these
      medications peri-operatively. We collected data on the use of warfarin at
      implantation, INR prior to device implantation, use of dual-antiplatelet therapy
      (DAPT), such as concomitant aspirin and clopidogrel and subsequent formation of
      hematoma in the peri-procedure period. RESULTS: PPM and ICD implantations were
      performed in 194 men and six women. The mean age was 73 years old. Fifty eight
      patients were taking warfarin with an average international normalized ratio of
      1.9 +/- 0.6; 112 were on ASA, 23 on clopidogrel, and 20 of them on DAPT. Only
      five patients were on DAPT and warfarin combined at the time of device
      implantation. Hematomas formed in a total of seven patients (3.5%), five of whom
      were on DAPT consisting of ASA and clopidogrel (P < 0.0001) while only two of
      them were on warfarin (P = 0.67). Pocket revision for hematoma evacuation was
      needed in four patients (2%), three of whom were on DAPT and only one on
      warfarin. CONCLUSION: This study suggests that hematoma formation after PPM or
      ICD implantation is rare, even among those who are anticoagulated. There were
      more patients with hematoma on DAPT than warfarin therapy and half of these
      patients with this complication needed pocket revision for evacuation. (PACE
      2010; 385-388).

PMID- 20059712
TI  - A decrease in serum aldosterone level is associated with maintenance of sinus
      rhythm after successful cardioversion of atrial fibrillation.
AB  - BACKGROUND: The activation of the renin-angiotensin-aldosterone system has been
      implicated in the progression of atrial structural remodeling during atrial
      fibrillation (AF). However, consequences of the changes of aldosterone in AF have
      not been evaluated. OBJECTIVES: This study's aim was to evaluate changes of serum
      aldosterone concentration after successful cardioversion of persistent AF and to
      determine the prognostic value of these changes. METHODS: The prospective, single
      center study included 45 consecutive patients with nonvalvular persistent AF and
      preserved left ventricular systolic function, referred for cardioversion. None of
      the patients were taking aldosterone antagonists. Blood samples for aldosterone
      measurement were collected twice: 24 hours before and 24 hours after
      cardioversion. RESULTS: Forty-three patients were successfully converted to sinus
      rhythm. On the 30th day following cardioversion, 24 patients maintained sinus
      rhythm (group A), 19 patients relapsed to AF (group B). Serum aldosterone
      concentration before cardioversion did not differ significantly between both
      groups (175.6 +/- 112.82 pg/mL vs 125.8 +/- 51.2 pg/mL; P = 0.25). However, in
      group A serum aldosterone level decreased significantly within 24 hours after
      cardioversion, from 175.6 +/- 112.8 pg/mL to 101.4 +/- 44.2 pg/mL (P = 0.0034).
      In group B, the aldosterone level before and after cardioversion did not differ
      significantly (125.8 +/- 51.2 pg/mL vs 118.2 +/- 59.6 pg/mL; P = 0.68). Logistic
      regression analysis revealed that a decrease in plasma aldosterone concentration
      after direct current cardioversion more than 13.2 pg/mL predicted sinus rhythm
      maintenance in a 30-day follow-up, with 87% sensitivity and 64% specificity.
      CONCLUSIONS: There is a positive correlation between the fall in aldosterone
      concentration 24 hours after cardioversion and maintenance of sinus rhythm during
      30 days of observation.

PMID- 20059713
TI  - Late gadolinium enhancement of the esophagus is common on cardiac MR several
      months after pulmonary vein isolation: preliminary observations.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) as a treatment for atrial fibrillation
      (AF) is commonly performed. This procedure can damage the esophagus. Late
      gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR)
      offers noninvasive assessment of scar. We sought to examine the prevalence of
      esophageal hyperenhancement on LGE-CMR prior to and following PVI. METHODS:
      Seventy-four patients underwent LGE-CMR prior to and 1.7 +/- 1.9 months post PVI
      for AF. Transmural esophageal hyperenhancement was visually assessed. The pre-
      and post PVI esophageal position was measured, relative to the vertebral body.
      RESULTS: Prior to PVI, 3% (2/74) of patients had esophageal LGE on CMR. At post
      PVI follow-up, 30% (23/74) of the studies demonstrated new esophageal
      hyperenhancement adjacent to an ablation site. Most (74%, 17/27) positive
      esophageal LGE studies were performed >30 days after PVI, while no (0/9) studies
      performed >2 months post PVI were positive for esophageal hyperenhancement. The
      presence of post-procedural esophageal hyperenhancement was not associated with
      longer ablation time (P = 0.42), use of an irrigated catheter (74% with LGE vs
      47% without, P = 0.16), right-sided esophageal location (56% with LGE vs 39%
      without, P = 0.17), size of left atrium cavity (58 +/- 8 mm with LGE vs 61 +/- 10
      mm without, P = 0.15), or the timing of the LGE-CMR study after PVI (36 +/- 10
      days with LGE vs 60 +/- 66 days without, P = 0.09). CONCLUSION: Though rare
      before PVI, new esophageal LGE is seen in almost one-third of patients after PVI.
      The clinical implications to remain to be explored, but clinicians should be
      aware of this frequent imaging finding.

PMID- 20059714
TI  - Implantation trends and patient profiles for pacemakers and implantable
      cardioverter defibrillators in the United States: 1993-2006.
AB  - BACKGROUND: Prior studies of cardiac rhythm management devices (pacemakers [PM]
      and implantable cardioverter defibrillators [ICD]) utilization in the United
      States have been limited to the Medicare population. We evaluated the national
      trends for the implantation of PMs and ICDs including the burden of device
      replacement. METHODS: The Nationwide Inpatient Sample was queried to identify PM
      and ICD patients between 1993 and 2006 using ICD-9-CM codes, including
      demographics, health profile, and economic data. The Charlson Comorbidity Index
      (CCI) and replacement burden were calculated, and changes over time studied.
      RESULTS: From 1993 to 2006, 2.4 million patients received a primary PM and 0.8
      million received an ICD, while there were 369,000 PM replacements and 74,000 ICD
      replacements. Women comprised 49% of PM and 24% of ICD patients. The mean ICD
      replacement burden was 8.4% (range 5-22%) and decreased significantly over time
      (P < 0.0001) while the replacement burden for PMs was constant (mean = 13.4%,
      range 11-16%). ICD patients had more comorbidities than PM patients (CCI: 0.8 vs
      1.1, P < 0.0001). CONCLUSIONS: The replacement burden for PMs has remained
      constant, while the replacement burden for ICDs has decreased. This is likely due
      to the stability of the patient population receiving PMs and technology maturity.
      Alternatively, the indications for ICD implantation have broadened, resulting in
      an increased number of primary ICD implantations. The age and comorbidities are
      increasing in those patients receiving ICDs while the PM population is stable.
      These data suggest that monitoring of replacement burden is warranted, given the
      changing populations, their disparate clinical outcomes, and economic
      implications to the health care system.

PMID- 20059716
TI  - High efficacy of disopyramide in the management of ventricular fibrillation
      storms in a patient with Brugada syndrome.
AB  - The patient was a 57-year-old man with Brugada syndrome, who had been implanted
      with a implantable cardioverter defibrillator (ICD). The frequency of ventricular
      fibrillation (VF) started to increase about 4 years after ICD implantation,
      occurring, at worst, six times in one night. Immediately after starting oral
      administration of disopyramide, VF stopped occurring. He then discontinued taking
      disopyramide, but immediately after the discontinuation VF started occurring
      again, so he restarted taking disopyramide. Thereafter, VF completely stopped
      occurring. Findings observed in our case suggest that disopyramide could be added
      in our arsenal of medications for treating arrhythmic storms in patient with
      Brugada syndrome.

PMID- 20059717
TI  - The appearance of ventricular preexcitation during exercise testing reproduced by
      dobutamine administration.
AB  - A 33-year-old woman presented with exercise-related palpitations after an
      apparently successful catheter-ablation of overt midseptal accessory pathway.
      Post procedure, the electrocardiogram at rest was normal, while the progressive
      appearance of delta-wave during treadmill stress testing was recorded. In
      addition, the occurrence of ventricular preexcitation was reproduced by
      controlled administration of dobutamine. Detailed understanding of the unusual
      pathway electrophysiology resulted in specific planning of the second procedure.
      In the basal state, pacing maneuvers did not demonstrate any evidence of pathway
      conduction. However, during infusion of dobutamine bidirectional conduction in
      the right anterior pathway was restored, enabling definitive cure by
      radiofrequency.

PMID- 20059718
TI  - Characteristics of telemetry interference with pacemakers caused by digital media
      players.
AB  - BACKGROUND: Contemporary implantable heart rhythm devices communicate multiple
      complex data simultaneously using radiofrequency telemetry. Interference in
      communication can expose them to the risk of potential corruption, leading to
      adverse clinical consequences. METHODS & RESULTS: We studied the characteristics
      of interference with uplink (real time intracardiac electrograms, marker channel,
      and stored histograms) and downlink (attempt to program a change in the lower
      rate limit, the pacing mode, and the ventricular lead configuration) data
      transmission between the wand and the pacemaker caused by digital media players
      (iPods--Photo and 3G) in 50 patients. We also measured and characterized worst
      case magnetic field emissions (MFE) from the wand (<or=0.4 microT), pacemaker
      (<or=0.004 microT), and iPod (<or=0.05 microT) during telemetry to understand the
      modulation techniques and safety protocols employed during data transmission.
      Telemetry interference (TI) manifested as high-frequency spikes (24.4%), blanking
      (17.7%) and interruption (22.2%), or delay (17.6%) in transmission with warning
      on programmer's screen. TI occurred in 25.6% of patients when the iPod was "on"
      and in 13% even with the iPod turned "off." There were no inaccuracies in
      downlinked data when the downlink communication was successful. Wanded telemetry
      utilizes low-frequency (30-300 kHz) radiowaves and simple digital modulation
      techniques at relatively slow rates for "sequential" data transmission protected
      by a continuous "handshake." Emissions from iPods in that range interrupt the
      telemetry link but are too weak to cause pacemaker malfunction through corruption
      of vital data. CONCLUSION: Low-power MFE from iPods can produce interference with
      establishment and maintenance of a telemetry link and can cause TI with
      transmission of real time data, but because of continuous check protocols, do not
      corrupt the stored and vital downlink data.

PMID- 20059719
TI  - Left ventricular ejection fraction and absence of ACE inhibitor/angiotensin II
      receptor blocker predicts appropriate defibrillator therapy in the primary
      prevention population.
AB  - INTRODUCTION: Implantable cardioverter defibrillators (ICD) significantly reduce
      mortality in patients with left ventricular (LV) dysfunction. However, little is
      known of the predictors of appropriate device activation in the primary
      prevention population. The aim of the present study was to determine predictors
      of appropriate device therapy in patients receiving ICDs for primary prevention.
      METHODS & RESULTS: One hundred twenty-six patients with a left ventricular
      ejection fraction (LVEF) of < 35% and no prior documented ventricular arrhythmias
      underwent ICD implantation. The ICD implanted was single chamber in 60 (48%),
      dual chamber in 10 (8%), and biventricular in 56 (44%) patients and programmed
      with a single ventricular fibrillation (VF) zone at >180 beats per minute. Mean
      age was 58 +/- 13 years and mean LVEF was 23 +/- 7%. Fifty-two percent had
      ischemic cardiomyopathy and 66% were New York Heart Association heart failure
      class II/III. During a mean follow-up period of 589 +/- 353 days, 17 (13%)
      patients received appropriate device therapy and three (4%) received
      inappropriate shocks. Appropriate ICD therapy was associated with reduced LVEF
      (mean 19.9% vs 23.7%, P = 0.02) and the patients were less likely to have
      received angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II
      receptor blockers (AIIRB) (65% vs 90%, P = 0.04). Multivariate analysis revealed
      lack of ACEI/AIIRB (odds ratio [OR]= 0.06, 95% confidence interval [CI]= 0.01
      0.37, P = <0.01) and lower LVEF (OR = 0.88, 95% CI 0.79-0.98, P = 0.02) predicted
      appropriate device activation. There was no difference in transplant-free
      survival between the appropriate therapy and no/inappropriate therapy groups,
      LVEF <20% and LVEF >20% group, and lack of ACEI/AIIRB and ACEI/AIIRB group.
      CONCLUSION: Appropriate device activation occurred in 13% of patients in a
      primary prevention population. LVEF and absence of ACEI/AIIRB predicted
      appropriate ICD therapy.

PMID- 20059720
TI  - Pro-con debate: is codeine a drug that still has a useful role in pediatric
      practice?

PMID- 20059721
TI  - Prevention of tracheal tube dislodgement and provision for reintubation during
      removal of laryngeal mask airway.

PMID- 20059722
TI  - Serum and urinary neutrophil gelatinase-associated lipocalin levels in children
      with chronic renal diseases.
AB  - BACKGROUND: Recent studies showed that serum and urinary neutrophil gelatinase
      associated lipocalin (NGAL) represents a novel, sensitive, specific biomarker for
      early detection of acute kidney injury. However, the clinical significance of
      measuring serum and urinary NGAL on chronic renal diseases remains unclear.
      METHODS: In this study, we measured serum and urinary NGAL levels in patients
      with several common pediatric renal diseases such as renal dysfunction (estimated
      glomerular filtration rate < 90 mL/min/1.73 m(2)), proliferative
      glomerulonephritis, steroid-resistant and steroid-sensitive nephrotic syndrome,
      and tubular dysfunction. RESULTS: Urinary NGAL level was significantly increased
      compared with the control in all of these disease groups except in patients with
      a remission stage of steroid-sensitive nephrotic syndrome, although a significant
      increase in serum NGAL level was observed in the renal dysfunction group only.
      Both serum and urinary NGAL levels showed significant inverse correlations with
      an estimated glomerular filtration rate in the analysis with total subjects, and
      also in the analysis with the renal dysfunction group in urinary NGAL. In
      proteinuric patients, the extent of proteinuria significantly correlated with
      urinary NGAL level. In patients with tubular dysfunction, the increase of urinary
      NGAL level was remarkable compared with the other disease groups. CONCLUSION:
      These results indicated that urinary NGAL level is a better biomarker for chronic
      renal diseases in children than serum NGAL level, although multiple pathological
      mechanisms should be considered in evaluating these NGAL values.

PMID- 20059723
TI  - High prevalence of antibodies against Bartonella henselae with cervical
      lymphadenopathy in children.
AB  - BACKGROUND: Cat-scratch disease is the most common form of Bartonella henselae
      infection. Although reports have shown that CSD is relatively common, they have
      not shown the prevalence of seropositivity for Bartonella henselae in cases of
      cervical lymphadenitis and Kawasaki disease, which are relatively common diseases
      in children. METHODS: We evaluated the presence of immunoglobulin (Ig) G- and IgM
      class antibodies against Bartonella henselae in children with cervical
      lymphadenitis, Kawasaki disease, and infectious diseases without lymphadenopathy
      in a semi-rural area in Japan. RESULTS: We found that the positivity rate for the
      IgG antibody against Bartonella henselae in patients with cervical lymphadenitis
      who owned cats or dogs was significantly higher than that in patients with
      Kawasaki disease and infectious diseases without lymphadenopathy. However, the
      average age of children with cervical lymphadenitis did not significantly differ
      when compared to those with other infectious diseases. CONCLUSION: Our
      serological study showed that Bartonella henselae infection may contribute to the
      etiology of cervical lymphadenitis in children.

PMID- 20059724
TI  - A reduced segment II/III graft for neonatal liver failure with absence of
      detectable hepatocytes. A case report and literature review.
AB  - When hepatic failure occurs in newborns, most cases are because of viral
      hepatitis, metabolic diseases, and neonatal hemochromatosis. It is rare to have
      liver failure presenting in the first day after birth. We report a unique case of
      a newborn baby with liver failure in the first day of life who received a reduced
      segment II and III graft when she was 19 days old and became the youngest
      survivor of LDLT. Common and rare causes of liver failure in this age group were
      excluded by appropriate testing. She underwent a liver biopsy that showed a liver
      devoid of hepatocytes. Similar pathological findings were found in the explanted
      liver. She was discharged from the hospital with normal graft function three
      months after the transplant.

PMID- 20059725
TI  - Minimal acute rejection in pediatric lung transplantation--does it matter?
AB  - In adult lung transplantation, a single minimal AR episode is a significant
      predictor of BOS independent of other factors. However, the significance of
      single minimal AR episodes in children is unknown. A retrospective, multi-center
      analysis was performed to determine whether isolated single AR episodes are
      associated with an increased BOS risk in children. Risk factors for BOS, death,
      or re-transplantation, and a combined outcome of BOS, death, or re
      transplantation were assessed. Original data included 577 patients (<21 yr of
      age). A total of 383 subjects were eligible for the study. Fifteen percent of
      patients developed BOS, and 13% of patients either died or underwent re
      transplant within one-yr post-transplant. In the multivariable survival model for
      time to BOS, there was no significant risk to developing BOS after a single
      minimal AR (A1) episode (HR 1.7, 95% CI 0.64-4.8; p=0.28). Even after a second
      minimal AR episode, no significant risk for BOS was appreciated. However, a
      single episode of mild AR (A2) was associated with twice the risk of BOS within
      one-yr post-transplant. In this select cohort, a single minimal AR episode was
      not associated with an increased risk for BOS within one yr following lung
      transplantation, in contrast to previous reports in adults.

PMID- 20059726
TI  - Reducing photoyellowing of wool using nano TiO2.
AB  - Wool is the most important animal fiber used in textile industries, but its
      photostability is very low. Scientists have searched for new ways to increase the
      photostability of wool. As TiO(2) nano particles have features suitable for new
      applications, the UV-blocking power of nano TiO(2) may be used for protecting
      fabrics against UV rays. Treatment of wool with TiO(2) can be effective for
      controlling photodegradation. This study focused on protecting wool fabric
      against UV rays using nano TiO(2). To this end, oxidized and raw wool were
      treated with citric acid as the cross-linking agent and different concentrations
      of nano TiO(2). The whiteness and yellowness of wool fabric samples were
      reported. XRD patterns proved the existence of TiO(2) nano-particles on the wool
      surface. Finally, the results revealed that nano TiO(2) is a suitable UV absorber
      on wool fabric and its effect depends on concentration.

PMID- 20059727
TI  - Solar UV geometric conversion factors: horizontal plane to cylinder model.
AB  - Most solar UV measurements are relative to the horizontal plane. However,
      problems arise when one uses those UV measurements to perform risk or benefit
      assessments because they do not yield the actual doses people get while they are
      outdoors. To better estimate the UV doses people actually get while outdoors,
      scientists need geometric conversion factors (GCF) that change horizontal plane
      irradiances to average irradiances on the human body. Here we describe a simple
      geometric method that changes unweighted, erythemally weighted and previtamin
      D(3)-weighted UV irradiances on the horizontal plane to full cylinder and
      semicylinder irradiances. Scientists can use the full cylinder model to represent
      the complete human body, while they can use the semicylinder model to represent
      the face, shoulders, tops of hands and feet. We present daily, monthly and
      seasonally calculated averages of the GCF for these cylinder models every 5
      degrees from 20 to 70 degrees N so that scientists can now get realistic UV doses
      for people who are outdoors doing a variety of different activities. The GCF show
      that people actually get less than half their annual erythemally weighted, and
      consequently half their previtamin D(3)-weighted, UV doses relative to the
      horizontal plane. Thus, scientists can now perform realistic UV risk and benefit
      assessments.

PMID- 20059728
TI  - Photochemistry of bacteriochlorophylls in human blood plasma: 2. Reaction
      mechanism investigated by product analysis and deuterium isotope effect.
AB  - Transmetalated (Pd) bacteriochlorophyll derivatives are currently being
      clinically tested as sensitizers for photodynamic therapy. Protocols using short
      delay times between injection and irradiation generate interest in the
      photochemistry of these pigments in the blood. Using near-infrared irradiation
      where these pigments absorb strongly, we have studied the mechanism of photo
      oxidation in two lipoprotein fractions, low- and high-density lipoproteins,
      derived from human blood plasma that preferentially accumulate these pigments
      (Dandler et al. [2009] Photochem. Photobiol., 85, in press). Using quenchers of
      reactive oxygen species, and chemical reporters, in particular peroxides
      generated from cholesterol as an inherent component of the lipoproteins, a Type
      II mechanism generating singlet oxygen has been demonstrated for Pd- and Zn
      bacteriopheophorbides. In homogeneous systems, accelerated bleaching in D(2)O,
      compared with H(2)O, supports this mechanism. An unusual deuterium isotope effect
      was observed, by contrast, in heterogeneous amphiphilic-water systems. In the
      early phase, and under high oxygen concentrations, again a positive D-isotope
      effect is observed which later, in a second phase, is reversed to a negative D
      isotope effect. The latter cannot be explained by heterogeneous pigment
      populations in the amphiphilic system; we, therefore, conclude a mechanistic
      switch, and discuss a possible mechanism.

PMID- 20059729
TI  - Ultraviolet radiation protection by a beach umbrella.
AB  - A beach umbrella intercepts all direct UV irradiance, but only part of the
      diffuse component. Using a simple sky view factor model, we have determined the
      fraction of the hemispheric diffuse irradiance that is not intercepted by the
      umbrella. Assuming a sensor at the surface and close to the center of the
      umbrella, isotropic diffuse irradiance and for an umbrella of 80 cm radius and
      100 cm high, our results show that approximately 34% of the incident horizontal
      irradiance is not intercepted by the umbrella. These results agree with
      irradiance measurements conducted with and without the umbrella. The model is
      next extended to examine receipt of UV radiation by a human figure in a vertical
      position, either standing or sitting.

PMID- 20059730
TI  - Influence of drought intensity on the response of six woody karst species
      subjected to successive cycles of drought and rewatering.
AB  - Tolerance to the effects of drought and subsequent recovery after a rainfall
      appear to be critical for plants in the karst regions of southwestern China,
      which are characterized by frequent but temporary drought events. This study
      investigated the effects of drought intensity and repetition on photosynthesis
      and photoprotection mechanisms of karst plants during successive cycles of
      drought and subsequent recovery. Leaf water potential, gas exchange, chlorophyll
      fluorescence and several associated metabolic processes were studied in six plant
      species, including Pyracantha fortuneana (PF), Rosa cymosa (RC), Broussonetia
      papyrifera (BP), Cinnamomum bodinieri (CB), Platycarya longipes (PL) and
      Pteroceltis tatarinowii (PT) during three cycles of drought treatments at four
      different intensities. The four treatments were: well-watered, mild drought,
      moderate drought and severe drought, each followed by rewatering events. We found
      that limitations to CO(2) diffusion accounted for photosynthetic declines under
      mild and moderate drought treatments, while metabolic limitations dominated the
      response to severe drought. Repetition of drought did not intensify the
      impairment of photosynthetic metabolism regardless of drought intensity in the
      six species studied. Repetition of severe drought delayed the photosynthetic
      recoveries in PF, RC and CB after rewatering. Repetition of drought increased
      thermal dissipation in PF, CB and BP, as well as superoxide dismutase (EC
      1.15.1.1) activity in RC and CB. Enhanced photosynthetic performance, measured as
      increased intrinsic water use efficiency, photosynthetic performance per unit of
      photosynthetic pigment, maintenance of high thermal dissipation and high ratios
      of carotenoids to chlorophylls, was observed during the rewatering periods. This
      enhanced photosynthetic performance allowed for the complete recovery of the six
      karst species from successive intermittent drought events.

PMID- 20059731
TI  - Reactive oxygen species and nitric oxide in plant mitochondria: origin and
      redundant regulatory systems.
AB  - Plant mitochondria differ from their mammalian counterparts in many respects,
      which are due to the unique and variable surroundings of plant mitochondria. In
      green leaves, plant mitochondria are surrounded by ample respiratory substrates
      and abundant molecular oxygen, both resulting from active photosynthesis, while
      in roots and bulky rhizomes and fruit carbohydrates may be plenty, whereas oxygen
      levels are falling. Several enzymatic complexes in mitochondrial electron
      transport chain (ETC) are capable of reactive oxygen species (ROS) formation
      under physiological and pathological conditions. Inherently connected parameters
      such as the redox state of electron carriers in the ETC, ATP synthase activity
      and inner mitochondrial membrane potential, when affected by external stimuli,
      can give rise to ROS formation via complexes I and III, and by reverse electron
      transport (RET) from complex II. Superoxide radicals produced are quickly
      scavenged by superoxide dismutase (MnSOD), and the resulting H(2)O(2) is
      detoxified by peroxiredoxin-thioredoxin system or by the enzymes of ascorbate
      glutathione cycle, found in the mitochondrial matrix. Arginine-dependent nitric
      oxide (NO)-releasing activity of enzymatic origin has been detected in plant
      mitochondria. The molecular identity of the enzyme is not clear but the
      involvement of mitochondria-localized enzymes responsible for arginine
      catabolism, arginase and ornithine aminotransferase has been shown in the
      regulation of NO efflux. Besides direct control by antioxidants, mitochondrial
      ROS production is tightly controlled by multiple redundant systems affecting
      inner membrane potential: NAD(P)H-dependent dehydrogenases, alternative oxidase
      (AOX), uncoupling proteins, ATP-sensitive K(+) channel and a number of matrix and
      intermembrane enzymes capable of direct electron donation to ETC. NO removal, on
      the other hand, takes place either by reactions with molecular oxygen or
      superoxide resulting in peroxynitrite, nitrite or nitrate ions or through
      interaction with non-symbiotic hemoglobins or glutathione. Mitochondrial ROS and
      NO production is tightly controlled by multiple redundant systems providing the
      regulatory mechanism for redox homeostasis and specific ROS/NO signaling.

PMID- 20059732
TI  - Obligatory short-day plant, Perilla frutescens var. crispa can flower in response
      to low-intensity light stress under long-day conditions.
AB  - An obligatory short-day plant, Perilla frutescens var. crispa was induced to
      flower under long-day conditions when grown under low-intensity light (30
      micromol m(-2) s(-1)). Plant size was smaller under lower light intensity,
      indicating that the low-intensity light acted as a stress factor. The phenomenon
      is categorized as stress-induced flowering. Low-intensity light treatment for 4
      weeks induced 100% flowering. The plants responded to low-intensity light
      immediately after the cotyledons expanded, and the flowering response decreased
      with increasing plant age. The induced plants produced fertile seeds, and the
      progeny developed normally. The plants that flowered under low-intensity light
      had greener leaves. This greening was because of the decrease in anthocyanin
      content, and there was a negative correlation between the anthocyanin content and
      percent flowering. Treatment with L-2-aminooxy-3-phenylpropionic acid, an
      inhibitor of phenylalanine ammonia-lyase (PAL), did not induce flowering under
      non-inductive light conditions and inhibited flowering under inductive low
      intensity light conditions. The metabolic pathway regulated by PAL may be
      involved in the flowering induced by low-intensity light.

PMID- 20059733
TI  - Analysis of expressed sequence tags from the Huperzia serrata leaf for gene
      discovery in the areas of secondary metabolite biosynthesis and development
      regulation.
AB  - Huperzia serrata produces various types of lycopodium alkaloids, especially the
      huperzine A (HupA) that is a promising drug candidate for Alzheimer's disease.
      Despite the medicinal importance of H. serrata, little genomic or transcriptomic
      data are available from the public databases. A cDNA library was thus generated
      from RNA isolated from the leaves of H. serrata. A total of 4012 clones were
      randomly selected from the library, and 3451 high-quality expressed sequence tags
      (ESTs) were assembled to yield 1510 unique sequences with an average length of
      712 bp. The majority (79.4%) of the unique sequences were assigned to the
      putative functions based on the BLAST searches against the public databases. The
      functions of these unique sequences covered a broad set of molecular functions,
      biological processes and biochemical pathways according to GO and KEGG
      assignments. The transcripts involved in the secondary metabolite biosynthesis of
      alkaloids, terpenoids and flavone/flavonoids, such as cytochrome P450, lysine
      decarboxylase (LDC), flavanone 3-hydroxylase, squalene synthetase and 2
      oxoglutarate 3-dioxygenase, were well represented by 34 unique sequences in this
      EST dataset. The corresponding peptide sequence of the LDC contained the Pfam
      03641 domain and was annotated as a putative LDC. The unique sequences encoding
      transcription factors, phytohormone biosynthetic enzymes and signaling components
      were also found in this EST collection. In addition, a total of 501 potential SSR
      motif microsatellite loci were identified from the 393 H. serrata leaf unique
      sequences. This set of non-redundant ESTs and the molecular markers obtained in
      this study will establish valuable resources for a wide range of applications
      including gene discovery and identification, genetic mapping and analysis of
      genetic diversity, cultivar identification and marker-assisted selections in this
      important medicinal plant.

PMID- 20059734
TI  - Characterization of a pathogenesis-related thaumatin-like protein gene TaPR5 from
      wheat induced by stripe rust fungus.
AB  - Pathogenesis-related (PR) proteins, induced in plants in response to various
      biotic and abiotic stresses, have been assumed to play a role in plant defense
      system. Proteins of the PR5 family, also named thaumatin-like proteins (TLPs),
      have been detected in numerous plant species. In this research, a novel PR5 gene,
      designated as TaPR5, was isolated and characterized from wheat leaves (cv. Suwon
      11) infected by the stripe rust pathotype CY23 (incompatible interaction) using
      the rapid amplification of cDNA ends (RACE). TaPR5 was predicted to encode a
      protein of 173 amino acids with an estimated molecular mass of 17.6 kDa and a
      theoretical pI of 4.64. The deduced amino acid sequence of TaPR5 showed a
      significant sequence similarity with PR5 and TLPs from barley and other plants
      and contained a putative signal peptide at the amino terminus. Southern blot
      analysis indicated that TaPR5 is coded by a single-copy gene. Quantitative real
      time polymerase chain reaction (qRT-PCR) analyses revealed that TaPR5 transcript
      is significantly induced and upregulated in the incompatible interaction while in
      the compatible interaction a relative low level of the transcript was detected.
      TaPR5 was also induced by phytohormones (SA, JA and ABA) and stress stimuli
      (wounding, cold temperature and high salinity). Using an assay of onion epidermal
      cells indicated accumulation of TaPR5 protein in the apoplast. The
      immunocytochemical method showed that the TaPR5 protein was detected on cell
      walls of wheat leaves in the incompatible interaction at markedly higher labeling
      density compared with the compatible interaction.

PMID- 20059735
TI  - Two Rubisco activase isoforms may play different roles in photosynthetic heat
      acclimation in the rice plant.
AB  - Studies on some plant species have shown that increasing the growth temperature
      gradually or pretreating with high temperature can lead to obvious photosynthetic
      acclimation to high temperature. To test whether this acclimation arises from
      heat adaptation of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco, EC
      4.1.1.39) activation mediated by Rubisco activase (RCA), gene expression of RCA
      large isoform (RCA(L)) and RCA small isoform (RCA(S)) in rice was determined
      using a 4-day heat stress treatment [40/30 degrees C (day/night)] followed by a 3
      day recovery under control conditions [30/22 degrees C (day/night)]. The heat
      stress significantly induced the expression of RCA(L) as determined by both mRNA
      and protein levels. Correlative analysis indicated that RCA(S) protein content
      was extremely significantly related to Rubisco initial activity and net
      photosynthetic rate (Pn) under both heat stress and normal conditions. Immunoblot
      analysis of the Rubisco-RCA complex revealed that the ratio of RCA(L) to Rubisco
      increased markedly in heat-acclimated rice leaves. Furthermore, transgenic rice
      plants expressing enhanced amounts of RCA(L) exhibited higher thermotolerance in
      Pn and Rubisco initial activity and grew better at high temperature than wild
      type (WT) plants and transgenic rice plants expressing enhanced amounts of
      RCA(S). Under normal conditions, the transgenic rice plants expressing enhanced
      amounts of RCA(S) showed higher Pn and produced more biomass than transgenic rice
      plants expressing enhanced amounts of RCA(L) and wild-type plants. Together,
      these suggest that the heat-induced RCA(L) may play an important role in
      photosynthetic acclimation to moderate heat stress in vivo, while RCA(S) plays a
      major role in maintaining Rubisco initial activity under normal conditions.

PMID- 20059736
TI  - WRKY6 is involved in the response to boron deficiency in Arabidopsis thaliana.
AB  - Boron (B) is one of the essential nutrients for plant growth and reproduction.
      Transcriptome analyses have identified genes regulated by B deficiency, but their
      function mostly remains elusive. To identify the functions of B deficiency
      inducible genes, T-DNA insertion mutants of 10 B deficiency-induced genes were
      obtained, and their growth properties in response to B conditions were examined.
      Among the lines examined, mutants of the transcription factor WRKY6 showed growth
      defect compared with the wild-type under B deficiency, but not under normal
      conditions. This growth defect was commonly observed among three independently
      isolated wrky6 mutants. There was no significant difference in B concentration
      between wrky6-3 and the wild-type. Promoter activity of WRKY6 was induced around
      the root tip under B deficiency. These results established that WRKY6 is a low-B
      induced transcription factor gene that is essential for normal root growth under
      low-B conditions. Transcriptome analysis around the root tip identified WRKY6
      regulated genes under B deficiency. Our findings represent the first
      identification of a transcription factor involved in the response to B
      deficiency.

PMID- 20059737
TI  - Simultaneous expression of choline oxidase, superoxide dismutase and ascorbate
      peroxidase in potato plant chloroplasts provides synergistically enhanced
      protection against various abiotic stresses.
AB  - Plants synthesize compatible solutes such as glycinebetaine (GB) in response to
      abiotic stresses. To evaluate the synergistic and protective effect of GB,
      transgenic potato plants expressing superoxide dismutase (SOD) and ascorbate
      peroxidase (APX) targeting to chloroplasts (referred to as SSA plants) were
      retransformed with a bacterial choline oxidase (codA) gene to synthesize GB in
      chloroplast in naturally occurring non-accumulator potato plants (including SSA)
      under the control of the stress-inducible SWPA2 promoter (referred to as SSAC
      plants). GB accumulation resulted in enhanced protection of these SSAC plants and
      lower levels of H(2)O(2) compared with SSA and non-transgenic (NT) plants after
      methyl viologen (MV)-mediated oxidative stress. Additionally, SSAC plants
      demonstrated synergistically enhanced tolerance to salt and drought stresses at
      the whole-plant level. GB accumulation in SSAC plants helped to maintain higher
      activities of SOD, APX and catalase following oxidative, salt and drought stress
      treatments than is observed in SSA and NT plants. Conclusively, GB accumulation
      in SSAC plants along with overexpression of antioxidant genes rendered the plants
      tolerant to multiple environmental stresses in a synergistic fashion.

PMID- 20059738
TI  - Interactive intoxicating and ameliorating effects of tannic acid, aluminum (Al),
      copper (Cu), and selenate (SeO) in wheat roots: a descriptive and mathematical
      assessment.
AB  - Tannic acids and tannins are produced by plants and are important components of
      soil and water organic matter. These polyphenolic compounds form complexes with
      proteins, metals and soil particulate matter and perform several physiological
      and ecological functions. The tannic acid (TA) used in our study was a mixture of
      gallic acid and galloyl glucoses ranging up to nonagalloyl glucose. TA inhibited
      root elongation in wheat seedlings (Triticum aestivum L. cv. Scout 66) at
      concentrations >4 mg l(-1); but TA alleviated the toxicity of Al(3+), Cu(2+) and
      SeO(4)(2-); and Al(3+) and SeO(4)(2-) alleviated the toxicity of TA. The
      interactions of Al(3+) and TA (each toxic but each alleviating the toxicity of
      the other) were stoichiometric. Growth was affected as though 1 kg TA bound 2.76
      mol Al so strongly that if (mol Al)/(kg TA) <2.76, then free Al approximately 0,
      and if (mol Al)/(kg TA) >2.76, then free TA approximately 0. This stoichiometry
      is consistent with one mole of galloyl groups binding approximately 0.5 mol Al.
      Using this binding scheme, growth was modeled successfully on the basis of free
      TA and free Al. TA enhanced the negativity of root surfaces and enhanced the
      binding of Al and Cu there without enhancing their toxicity. These and other
      interactions among TA, Al(3+), Cu(2+), SeO(4)(2-), Ca(2+), Na(+) and H(+) were
      quantified with a comprehensive non-linear equation with statistically
      significant coefficients.

PMID- 20059739
TI  - Importance of AOX pathway in optimizing photosynthesis under high light stress:
      role of pyruvate and malate in activating AOX.
AB  - The present study shows the importance of alternative oxidase (AOX) pathway in
      optimizing photosynthesis under high light (HL). The responses of photosynthesis
      and respiration were monitored as O(2) evolution and O(2) uptake in mesophyll
      protoplasts of pea pre-incubated under different light intensities. Under HL
      (3000 micromol m(-2) s(-1)), mesophyll protoplasts showed remarkable decrease in
      the rates of NaHCO(3)-dependent O(2) evolution (indicator of photosynthetic
      carbon assimilation), while decrease in the rates of respiratory O(2) uptake were
      marginal. While the capacity of AOX pathway increased significantly by two fold
      under HL, the capacity of cytochrome oxidase (COX) pathway decreased by >50%
      compared with capacities under darkness and normal light (NL). Further, the total
      cellular levels of pyruvate and malate, which are assimilatory products of active
      photosynthesis and stimulators of AOX activity, were increased remarkably
      parallel to the increase in AOX protein under HL. Upon restriction of AOX pathway
      using salicylhydroxamic acid (SHAM), the observed decrease in NaHCO(3)-dependent
      O(2) evolution or p-benzoquinone (BQ)-dependent O(2) evolution [indicator of
      photosystem II (PSII) activity] and the increase in total cellular levels of
      pyruvate and malate were further aggravated/promoted under HL. The significance
      of raised malate and pyruvate levels in activation of AOX protein/AOX pathway,
      which in turn play an important role in dissipating excess chloroplastic reducing
      equivalents and sustenance of photosynthetic carbon assimilation to balance the
      effects of HL stress on photosynthesis, was depicted as a model.

PMID- 20059740
TI  - Flowering and dwarfism induced by DNA demethylation in Pharbitis nil.
AB  - Flowering and dwarfism induced by 5-azacytidine and zebularine, which both cause
      DNA demethylation, were studied in a short-day (SD) plant Pharbitis nil (synonym
      Ipomoea nil), var. Violet whose photoinduced flowering state does not last for a
      long period of time. The DNA demethylating reagents induced flowering under non
      inductive long-day (LD) conditions. The flower-inducing effect of 5-azacytidine
      did not last for a long period of time, and the plants reverted to vegetative
      growth. The progeny of the plants that were induced to flower by DNA
      demethylation did not flower under the non-inductive photoperiodic conditions.
      These results suggest that the flowering-related genes were activated by DNA
      demethylation and then remethylated again in the progeny. The DNA demethylation
      also induced dwarfism. The dwarfism did not last for a long period of time, was
      not heritable and was overcome by gibberellin A3 but not by t-zeatin or kinetin.
      The change in the genome-wide methylation state was examined by methylation
      sensitive amplified fragment length polymorphism (MS-AFLP) analysis. The analysis
      detected many more polymorphic fragments between the DNA samples isolated from
      the cotyledons treated with SD than from the cotyledons under LD conditions,
      indicating that the DNA methylation state was altered by photoperiodic
      conditions. Seven LD-specific fragments were extracted from the gel of the MS
      AFLP and were sequenced. One of these fragments was highly homologous with the
      genes encoding ribosomal proteins.

PMID- 20059741
TI  - Cloning and characterization of a UV-B-inducible maize flavonol synthase.
AB  - Flavonols are important compounds for conditional male fertility in maize (Zea
      mays) and other crops, and they also contribute to protecting plants from UV-B
      radiation. However, little continues to be known on how maize and other grasses
      synthesize flavonols, and how flavonol biosynthesis is regulated. By homology
      with an Arabidopsis flavonol synthase (AtFLS1), we cloned a maize gene encoding a
      protein (ZmFLS1) capable of converting the dihydrokaempferol (DHK) and
      dihydroquercetin (DHQ) dihydroflavonols to the corresponding flavonols,
      kaempferol (K) and quercetin (Q). Moreover, ZmFLS1 partially complements the
      flavonol deficiency of the Arabidopsis fls1 mutant, and restores anthocyanin
      accumulation to normal levels. We demonstrate that ZmFLS1 is under the control of
      the anthocyanin (C1/PL1 + R/B) and 3-deoxy flavonoid (P1) transcriptional
      regulators. Indeed, using chromatin immunoprecipitation (ChIP) experiments, we
      establish that ZmFLS1 is an immediate direct target of the P1 and C1/R regulatory
      complexes, revealing similar control as for earlier steps in the maize flavonoid
      pathway. Highlighting the importance of flavonols in UV-B protection, we also
      show that ZmFLS1 is induced in maize seedlings by UV-B, and that this induction
      is in part mediated by the increased expression of the P1, B and PL1 regulators.
      Together, our results identify a key flavonoid biosynthetic enzyme so far missed
      in maize and other monocots, and illustrate mechanisms by which flavonol
      accumulation is controlled in maize.

PMID- 20059742
TI  - Methyl salicylate production in tomato affects biotic interactions.
AB  - The role of methyl salicylate (MeSA) production was studied in indirect and
      direct defence responses of tomato (Solanum lycopersicum) to the spider mite
      Tetranychus urticae and the root-invading fungus Fusarium oxysporum f. sp.
      lycopersici, respectively. To this end, we silenced the tomato gene encoding
      salicylic acid methyl transferase (SAMT). Silencing of SAMT led to a major
      reduction in SAMT expression and MeSA emission upon herbivory by spider mites,
      without affecting the induced emission of other volatiles (terpenoids). The
      predatory mite Phytoseiulus persimilis, which preys on T. urticae, could not
      discriminate between infested and non-infested SAMT-silenced lines, as it could
      for wild-type tomato plants. Moreover, when given the choice between infested
      SAMT-silenced and infested wild-type plants, they preferred the latter. These
      findings are supportive of a major role for MeSA in this indirect defence
      response of tomato. SAMT-silenced tomato plants were less susceptible to a
      virulent strain of F. oxysporum f. sp. lycopersici, indicating that the direct
      defense responses in the roots are also affected in these plants. Our studies
      show that the conversion of SA to MeSA can affect both direct and indirect plant
      defence responses.

PMID- 20059744
TI  - DNA fragmentation in canine immature grade 1 cumulus-oocyte complexes.
AB  - In this work, we studied the incidence of DNA fragmentation, interpreted as
      apoptotic changes and assessed by the TUNEL assay, in cumulus cells and oocytes
      of immature Grade 1 cumulus-oocyte complexes (COCs) obtained from healthy bitches
      (n = 27) of three age groups: young (1-3 years; n = 13), adult (4-6 years; n = 8)
      and elderly (7-10 years; n = 6). Age affected (p < 0.05) Grade 1 COCs recovery
      rates, with young animals yielding more (p < 0.01) Grade 1 COCs than the other
      two age groups. Conversely, no differences were observed in the incidence of DNA
      fragmentation (TUNEL-positive) in cumulus cells or oocytes between the three age
      groups. Overall, more than 80% of Grade 1 COCs presented <15% of TUNEL-positive
      cumulus cells and enclosed TUNEL-negative (intact DNA) oocytes. Despite a higher
      proportion of TUNEL-negative oocytes being found in the germinal vesicle stage,
      most of the oocytes with nuclear material compatible with meiosis resumption (MR)
      or with non-identifiable nuclear material (ND) did not present DNA fragmentation.
      No correlation was observed between DNA fragmentations in oocytes and in cumulus
      cells. We concluded that the morphological parameters used to classify canine
      Grade 1 COCs are reliable to select a homogeneous population of COCs with low
      incidence of DNA fragmentation. Furthermore, these results indicate that DNA
      fragmentation can only explain a minor proportion of the incidence of MR and
      degeneration in canine oocytes at collection.

PMID- 20059743
TI  - An SGS3-like protein functions in RNA-directed DNA methylation and
      transcriptional gene silencing in Arabidopsis.
AB  - RNA-directed DNA methylation (RdDM) is an important epigenetic mechanism for
      silencing transgenes and endogenous repetitive sequences such as transposons. The
      RD29A promoter-driven LUCIFERASE transgene and its corresponding endogenous RD29A
      gene are hypermethylated and silenced in the Arabidopsis DNA demethylase mutant
      ros1. By screening for second-site suppressors of ros1, we identified the RDM12
      locus. The rdm12 mutation releases the silencing of the RD29A-LUC transgene and
      the endogenous RD29A gene by reducing the promoter DNA methylation. The rdm12
      mutation also reduces DNA methylation at endogenous RdDM target loci, including
      transposons and other repetitive sequences. In addition, the rdm12 mutation
      affects the levels of small interfering RNAs (siRNAs) from some of the RdDM
      target loci. RDM12 encodes a protein with XS and coiled-coil domains, and is
      similar to SGS3, which is a partner protein of RDR6 and can bind to double
      stranded RNAs with a 5' overhang, and is required for several post
      transcriptional gene silencing pathways. Our results show that RDM12 is a
      component of the RdDM pathway, and suggest that RdDM may involve double-stranded
      RNAs with a 5' overhang and the partnering between RDM12 and RDR2.

PMID- 20059745
TI  - Oocyte morphology from primordial to early tertiary follicles of yak.
AB  - The objective of this study was to investigate the developmental morphology of
      yak oocytes from the primordial follicle to the tertiary follicle. Yak oocytes
      from resting primordial (n = 6), activated primordial (n = 12), primary (n = 9),
      secondary (n = 7) and early tertiary (n = 5) follicles were processed and
      analysed by light and transmission electron microscopy. The resting primordial
      follicular oocyte was characterized by relatively smooth surface on the oolemma,
      the accumulation of free and organelle-related smooth (SER) and rough endoplasmic
      reticulum (RER), round or oval mitochondria, and polyribosomes on the surface of
      the RER and throughout the ooplasm. The activated primordial follicular oocyte
      was dominated by numerous coated pits and coated vesicles on the oolemma, and
      round mitochondria. Up to the secondary follicular stage the oocyte displayed an
      increase in the number of microvilli, polyribosome, Golgi complexes and
      mitochondria with distinct cristae. During the secondary follicular stage,
      formation of the zona pellucida, development of a desmosome-like connection
      between the oocyte and the granulosa cells, formation of the cortical granules in
      the oocyte and elongated mitochondria in nearly all oocytes were seen. In the
      early tertiary follicular oocyte, the perivitelline space was present and a
      decrease in free SER and RER in the ooplasm occurred; finally, the nucleus
      migrated from an eccentric to a peripheral location. In conclusion, the growth of
      the yak oocyte is associated with the relocation and modulation of a number of
      cytoplasmic organelles as well as the development of oocyte-specific structures
      such as the zona pellucida, desmosome-like connection and cortical granules.

PMID- 20059746
TI  - Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates
      constitutive autophagy.
AB  - Autophagy is a catabolic process that delivers cytoplasmic material to the
      lysosome for degradation. The mechanisms regulating autophagosome formation and
      size remain unclear. Here, we show that autophagosome formation was triggered by
      the overexpression of a dominant-negative inactive mutant of Myotubularin-related
      phosphatase 3 (MTMR3). Mutant MTMR3 partially localized to autophagosomes, and
      PtdIns3P and two autophagy-related PtdIns3P-binding proteins, GFP-DFCP1 and GFP
      WIPI-1alpha (WIPI49/Atg18), accumulated at sites of autophagosome formation.
      Knock-down of MTMR3 increased autophagosome formation, and overexpression of wild
      type MTMR3 led to significantly smaller nascent autophagosomes and a net
      reduction in autophagic activity. These results indicate that autophagy
      initiation depends on the balance between PI 3-kinase and PI 3-phosphatase
      activity. Local levels of PtdIns3P at the site of autophagosome formation
      determine autophagy initiation and the size of the autophagosome membrane
      structure.

PMID- 20059747
TI  - Regulation of G-protein coupled receptor traffic by an evolutionary conserved
      hydrophobic signal.
AB  - Plasma membrane (PM) expression of G-protein coupled receptors (GPCRs) is
      required for activation by extracellular ligands; however, mechanisms that
      regulate PM expression of GPCRs are poorly understood. For some GPCRs, such as
      alpha2c-adrenergic receptors (alpha(2c)-ARs), heterologous expression in non
      native cells results in limited PM expression and extensive endoplasmic reticulum
      (ER) retention. Recently, ER export/retentions signals have been proposed to
      regulate cellular trafficking of several GPCRs. By utilizing a chimeric
      alpha(2a)/alpha(2c)-AR strategy, we identified an evolutionary conserved
      hydrophobic sequence (ALAAALAAAAA) in the extracellular amino terminal region
      that is responsible in part for alpha(2c)-AR subtype-specific trafficking. To our
      knowledge, this is the first luminal ER retention signal reported for a GPCR.
      Removal or disruption of the ER retention signal dramatically increased PM
      expression and decreased ER retention. Conversely, transplantation of this
      hydrophobic sequence into alpha(2a)-ARs reduced their PM expression and increased
      ER retention. This evolutionary conserved hydrophobic trafficking signal within
      alpha(2c)-ARs serves as a regulator of GPCR trafficking.

PMID- 20059748
TI  - Lipids on trial: the search for the offending metabolite in Niemann-Pick type C
      disease.
AB  - Niemann-Pick disease type C is a complex lysosomal storage disorder caused by
      mutations in either the NPC1 or NPC2 genes that is characterized at the cellular
      level by the storage of multiple lipids, defective lysosomal calcium homeostasis
      and unique trafficking defects. We review the potential role of each of the
      individual storage lipids in initiating the pathogenic cascade and propose a
      model of NPC1 and NPC2 function based on the current knowledge.

PMID- 20059749
TI  - Establishing a role for the GTPase Ypt1p at the late Golgi.
AB  - GTPases of the Rab family cycle between an inactive (GDP-bound) and active (GTP
      bound) conformation. The active form of the Rab regulates a variety of cellular
      functions via multiple effectors. Guanine nucleotide exchange factors (GEFs)
      activate Rabs by accelerating the exchange of GDP for GTP, while GTPase
      activating proteins (GAPs) inactivate Rabs by stimulating the hydrolysis of GTP.
      The GTPase Ypt1p is required for endoplasmic reticulum (ER)-Golgi and intra-Golgi
      traffic in the yeast Saccharomyces cerevisiae. Recent findings, however, have
      shown that Ypt1p GEF, GAP and an effector are all required for traffic from the
      early endosome to the Golgi. Here we describe a screen for ypt1 mutants that
      block traffic from the early endosome to the late Golgi, but not general
      secretion. This screen has led to the identification of a collection of recessive
      and dominant mutants that block traffic from the early endosome. While it has
      long been known that Ypt1p regulates the flow of biosynthetic traffic into the
      cis side of the Golgi, these findings have established a role for Ypt1p in the
      regulation of early endosome-Golgi traffic. We propose that Ypt1p regulates the
      flow of traffic into the cis and trans side of the Golgi via multiple effectors.

PMID- 20059750
TI  - The significance of repeat testing in Turkish blood donors screened with HBV, HCV
      and HIV immunoassays and the importance of S/CO ratios in the interpretation of
      HCV/HIV screening test results and as a determinant for further confirmatory
      testing.
AB  - The purpose of this study was to investigate the intra-assay correlations amongst
      initial reactive and repeat screening results used in enzyme immunoassays (EIAs)
      for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV in blood donors.
      This study evaluated the value of using the power of the signal to cut-off (S/CO)
      ratio index for confirming anti-HCV/HIV reactive screening results, thereby
      touching upon the utility of S/CO indices in determining whether further
      confirmatory testing was necessary. Screening test results of the 72,695 blood
      donors were evaluated over a 1-year period. Correlation analysis among each
      initial test and retests was done by Pearson r test. Appropriate S/CO values to
      determine the need of the confirmation testing was investigated by ROC analyses.
      EIA intra-assay correlations were of statistical significance and were determined
      as follows: 0.948 for anti-HCV, 0.827 for anti-HIV and 0.948 for HBsAg. The
      threshold S/CO ratio values which predicted more than 95% of the confirmation
      test result were 3.8 for HCV and 5.6 for HIV. We were able to demonstrate a
      strong level of intra-assay correlation amongst EIAs, thereby eliminating the
      need for repetition of the screening test. Hence, we suggest that repeat
      screening should only be limited to HBV and HIV tests with low EIA S/CO ratios.
      Thus, using the power of the S/CO ratio in determining the need for HCV
      confirmation testing can be a cost-effective measure, especially if the S/CO
      value is >or=3.8.

PMID- 20059751
TI  - Twenty four-hour ambulatory blood pressure profiles 12 months post living kidney
      donation.
AB  - Summary Small blood pressure (BP) elevations may occur post kidney donation. This
      prospective study determined 24-h ambulatory BP (ABP) and other cardiovascular
      risk factor changes in 51 living donors over 12 months postdonation. Donors also
      provided 24-h urine collections for monitoring protein and creatinine clearance,
      75 g oral glucose tolerance tests (OGTT), and fasting lipids. Nondipping was
      defined as night-day systolic (SBP) ratio >or=0.9. Baseline and 12-month pre to
      postdonation comparisons were made both for dippers and nondippers. Of 51 donors,
      35 were dippers and 16 nondippers. In these two groups, predonation 24-h SBP were
      115.2 +/- 8 and 115.6 +/- 10 mmHg; serum creatinine (SCr) 69.3 +/- 12 and 71.1 +/
      13 micromol/l; and 24-h urine protein 0.12 +/- 0.05 and 0.09 +/- 0.03 g (all P =
      NS) while at 12 months, 24-h SBP were 111.4 +/- 11 and 114.3 +/- 8 mmHg (P =
      0.384), SCr 97.9 +/- 16 and 97.7 +/- 21 micromol/l (P = 0.810); and 24-h urine
      protein 0.139 +/- 0.09 and 0.111 +/- 0.07 g/d (P = 0.360) respectively. The 24-h
      SBP was significantly lower in the dippers at 12 months as compared with
      predonation (P = 0.036). OGTT and lipid profiles remained normal in both groups.
      Predonation nocturnal nondipping does not carry adverse postdonation consequences
      over 12 months.

PMID- 20059752
TI  - The number of lung transplants can be safely doubled using extended criteria
      donors; a single-center review.
AB  - Relaxing the standard lung donor criteria may significantly increase the reported
      15% organ yield but post-transplant recipient outcome should be carefully
      monitored. Charts from all consecutive deceased organ donors within our hospital
      network were reviewed over a 2-year period. Reasons for lung refusals and number
      of lungs transplanted were analysed. Hospital outcome including early recipient
      survival was compared between standard- and extended criteria donors. Out of 283
      referrals, 164 (58%) qualified as donor of any organ. The majority (65.9%) of
      these effective donors were declined for lung donation because of chest X-ray
      abnormalities (20%), age >70 years (13%), poor oxygenation (10%), or aspiration
      (9%). Out of 56 (34.1%) accepted lung donors, 50 transplants were performed at
      our center, 23 from standard criteria donors versus 27 from extended criteria
      donors. There were no significant differences in hospital outcome and in early
      survival between lung recipients from both donor groups. Lung acceptance rate
      (34.1%) in our donor network is 10-20% higher than reported figures. The number
      of lung transplants in our center doubled by accepting extended criteria donors.
      This policy did not negatively influence our results after lung transplantation.

PMID- 20059753
TI  - Feline platelet counting with prostaglandin E1 on the Sysmex XT-2000iV.
AB  - BACKGROUND: The large size of many feline platelets and the high frequency of
      platelet aggregation often results in falsely low platelet counts in this
      species. A combination of optical platelet counting to detect even large
      platelets and the use of prostaglandin E1 (PGE1) to inhibit platelet clumping may
      increase the accuracy of feline platelet counting. OBJECTIVE: The objective of
      this study was to compare platelet counts in feline whole blood samples with and
      without the addition of PGE1 and using different analytical methods in a clinical
      setting. METHODS: Platelet counts were determined in 10 feline patients in a
      referral veterinary hospital using 2 sample types (EDTA, EDTA with PGE1) and 2
      methods of analysis (optical counting [PLT-O] and impedance counting [PLT-I]) on
      the Sysmex XT 2000 iV analyzer. RESULTS: All PGE1-PLT-O samples had platelet
      counts of >200 x 10(9)/L. Mean platelet count using PGE1-PLT-O (410,256+/-178 x
      10(9)/L) was significantly higher (P<.03) compared with PGE1-PLT-I (256+/-113 x
      10(9)/L), EDTA-PLT-O (238+/-107 x 10(9)/L), and EDTA-PLT-I (142+/-84 x 10(9)/L)
      methods. Depending on the method, platelet counts in 2 to 7 of 10 cats were <200
      x 10(9)/L when PGE1-PLT-O was not used. A slightly increased platelet count in
      response to treatment of a feline patient with thrombocytopenia would have been
      missed without use of PGE1-PLT-O. CONCLUSIONS: Using PLT-O analysis on EDTA
      samples containing PGE1 provides higher, and therefore likely more accurate,
      feline platelet counts in a clinical setting.

PMID- 20059754
TI  - Evaluation of albuminuria and its relationship with blood pressure in dogs with
      chronic kidney disease.
AB  - BACKGROUND: Microalbuminuria and hypertension have long been associated with a
      guarded prognosis in human patients with a variety of diseases. In veterinary
      medicine, tests for microalbuminuria have been used for detecting early kidney
      damage, but there is little information regarding its association with high blood
      pressure in dogs with chronic kidney disease (CKD). OBJECTIVE: The objective of
      this study was to evaluate albuminuria and its association with arterial
      hypertension in dogs with CKD. METHODS: Urinary albumin:creatinine (UAC) ratio,
      urinary protein:creatinine (UPC) ratio, and systolic blood pressure were
      determined in 39 clinically healthy dogs and 40 dogs with CKD. RESULTS: UAC in
      dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from
      that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC
      0.03-0.3) and macroalbuminuria (UAC>0.3) were detected in 32.5% and 50% of dogs
      with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic
      pressure > or =180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median,
      1.72) was significantly higher than in dogs with CKD and systolic pressure<180
      mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with
      UPC>1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had
      microalbuminuria, and those with UPC<0.5 usually lacked albuminuria. CONCLUSIONS:
      UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests
      designed to detect microalbuminuria may be useful for hypertensive dogs with CKD
      and a UPC < or = 1.0 to detect the onset and magnitude of albuminuria. Once
      macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

PMID- 20059755
TI  - Plasma protein electrophoresis of Trachemys scripta and Iguana iguana.
AB  - BACKGROUND: Protein electrophoresis is widely applied in veterinary medicine, but
      is not used often in reptiles, in part because of lack of reference values.
      OBJECTIVE: The goals of this study were to compare plasma protein profiles
      obtained by cellulose acetate electrophoresis (CAE) and agarose gel
      electrophoresis (AGE), measure precision and examine interference by sample
      hemolysis, and establish preliminary reference intervals for 2 reptile species.
      METHODS: Heparinized plasma samples from healthy and diseased adult female Iguana
      iguana (n=40) and Trachemys scripta (n=60) were analyzed by CAE and AGE. Total
      protein concentration was measured by the biuret method. Electrophoresis results
      were compared using Bland-Altman plots and Passing-Bablok regression analysis.
      Precision and the effects of sample hemolysis were determined. Results from
      clinically healthy animals were used to determine reference intervals. RESULTS:
      Five protein fractions were identified in both species, with bisalbuminemia
      observed in 23/40 iguanas. High correlation was observed between the 2 methods
      for all fractions, with few proportional and systematic errors. Coefficients of
      variation were lower using AGE vs CAE and for I. iguana vs T. scripta. Two
      additional bands were observed in hemolyzed samples from T. scripta; 1 additional
      band was observed for I. iguana. Minimum and maximum values were reported for
      healthy I. iguana (n=14) and T. scripta (n=22). CONCLUSIONS: Although both
      methods are acceptable, the performance of AGE was slightly better than that of
      CAE for analysis of plasma from reptiles. Furthermore, reptile electrophoretic
      patterns should be interpreted based on the method used, the species analyzed,
      and the quality of the plasma sample.

PMID- 20059756
TI  - Red blood units collected from bone marrow harvests after mononuclear cell
      selection qualify for autologous use.
AB  - BACKGROUND: After large volume bone marrow (BM) harvest, donors and patients can
      develop severe anaemia, because collected BM can contain up to 20% of their red
      cell mass. In a prospective analysis, we investigated the feasibility to recover
      red blood cells (RBCs) from the harvested BM and investigated whether these RBC
      units meet the quality requirements of the European Council. PATIENTS AND
      METHODS: From 19 patients (median age 51 yrs, range 31-77) with acute myocardial
      infarction, who participated in the MYSTAR study, a median volume of 1299 ml
      (range, 700-1870 ml) BM was collected. During BM processing, mononuclear cells
      (MNC) were separated using the Cobe Spectra apheresis system and the residual
      RBCs were collected in a separate bag. The quality of the collected RBCs was
      assessed by measuring LDH, free haemoglobin, potassium and lactate. Haemolysis
      was calculated and the intracellular concentration of ATP, ADP, AMP was
      determined by HPLC. RESULTS: RBC units recovered from BM after MNC separation had
      a mean volume of 312 +/- 95 ml with a haematocrit of 47 +/- 8.9%, a haemoglobin
      content of 51 +/- 15 g per unit, a haemolysis of 0.15 +/- 0.005%, a pH of 6.8 +/-
      0.007 and an intracellular ATP concentration of 135 pmol/10(6) RBC +/- 41, which
      is comparable with freshly collected packed red blood cells (PRBCs). CONCLUSION:
      RBCs, collected from bone marrow harvests, can be used for autologous blood
      support to minimize allogeneic blood transfusions in donors and patients after
      large volume BM donation.

PMID- 20059757
TI  - Analysis of Wnt pathway genes during ex vivo expansion and neutrophil
      differentiation of umbilical-cord-blood-derived CD34 cells.
AB  - Previous work has shown that optimal ex vivo expansion and differentiation of
      CD34(+) progenitor cells into neutrophils is by addition of Flt3-L, SCF and G
      CSF. Here we report that a variety of genes involved in the WNT pathway are
      transcriptionally active in both undifferentiated and differentiated umbilical
      cord blood CD34(+) cells, however statistically significant changes in gene
      expression are not always consistent across UCB samples.

PMID- 20059758
TI  - Blood product collection and supply: a matter of money?
AB  - BACKGROUND: Previous studies have shown that countries with a low or medium Human
      Development Index (HDI) transfuse far fewer blood products than countries with a
      high HDI. HDI comprises both economical and non-economical elements. We
      considered the hypothesis that non-economical, cultural differences may be
      additional factors in understanding blood donation and blood supply differences.
      METHODS: We quantified the explained variance, r(2), in: the number of donors,
      the number of whole blood collections and the number of red blood cell units
      supplied to hospitals for 25 European countries. Candidate predictors were
      Hofstede's cultural dimensions, the demographic factor Old Age Dependency Ratio
      and the three components of HDI: Gross National Income, Life Expectancy and the
      Educational Development Index. RESULTS: The cultural dimension Power Distance was
      the best sole predictor of whole blood collection (r(2) = 56.8%) and the number
      of donors (r(2) = 25.1%). The Educational Development Index best predicted the
      number of red blood cell units (r(2) = 45.0%). Multivariable models including the
      cultural dimension Power Distance and the Educational Development Index gave the
      best results in predicting the number of whole blood collections and red blood
      cell units supplied and, to a lesser extent, the number of donors, with adjusted
      r(2) values of 63.6%, 51.9% and 28.6%, respectively. In contrast, Gross National
      Income made no significant predictive contribution to any of the multivariable
      models. Neither did the other cultural dimensions, Life Expectancy or Old Age
      Dependency Ratio. CONCLUSION: The effects of education level and cultural aspects
      should be taken into account as influencers on donation behaviour. The concept of
      power distance, in particular, presents a challenge to blood donor managers in
      cross-cultural and multi-cultural donor management contexts.

PMID- 20059759
TI  - The interface between blood preparation and use in Uganda.
AB  - BACKGROUND AND OBJECTIVES: The interface between preparation and use of blood
      impacts directly on the outcome of hemotherapy. The present study explores the
      knowledge and opinions of key players at, practical realities at, and quality
      improvement strategies of this interface. MATERIALS AND METHODS: We surveyed
      clinicians (n = 81) and blood bank staff (n = 25) to assess their knowledge on
      key issues in their counterparts' working domains, the turnaround time on
      effecting a blood order from a hospital transfusion laboratory and strategies to
      improve communication of blood needs to blood banks. RESULTS: Out of 81
      clinicians, 20 knew the four available blood products while only 17 knew the
      three uses of these products. Twenty-three blood bank staff reported the
      patient's condition as the main factor on which blood orders are based. Forty
      four (54.3%) clinicians reported reception of a blood product within an hour of
      placing the order. Addressing infrastructure and human resource were some of the
      strategies suggested to improve this step of the transfusion chain. CONCLUSIONS:
      The knowledge of staff at the extreme ends of the clinical interface in their
      counterparts' working domain is far from adequate. However, they have well formed
      opinions on strategies to improve this interface.

PMID- 20059760
TI  - Buffy-coat-derived pooled platelet concentrates and apheresis platelet
      concentrates: which product type should be preferred?
AB  - There is an ongoing debate whether platelet concentrates (PCs) prepared from
      either whole-blood donations or by plateletpheresis are superior. Usage of these
      two product types varies greatly between countries and individual institutions.
      Some use mainly apheresis PCs; others prefer pooled PCs which are produced from
      whole-blood donations. This review summarizes the existing information on these
      product types. In the first part data on quality, efficacy and safety are
      reviewed. It is important to note that the issue cannot be answered just by
      comparing 'the' apheresis platelet concentrate versus 'the' pooled platelet
      concentrate. Other factors which determine the quality of a product, e.g.
      residual leukocyte count, plasma content, additive solution or storage period may
      be even more important. The focus of the debate should be shifted. It is much
      more needed to further improve the overall quality of PCs and to optimize
      treatment of thrombocytopenic patients than to concentrate on a single-edged view
      on just the preparation method. In the second part of this review we compare the
      product types from the donor's point of view. If PCs which are equally safe and
      effective can be obtained by various methods, ethics and the safety of the
      healthy volunteer donor tips the scales. The decision on the use of a particular
      product type should take into account all aspects of efficacy, side effects and
      availability of the product as well as the donor's perspective and the commitment
      to maximize the use of the valuable whole-blood donation.

PMID- 20059761
TI  - Varying postprandial abdominovagal and cardiovagal activity in normal subjects.
AB  - BACKGROUND: Several studies have supported the hypothesis of different
      presentations in the autonomic nervous system (ANS) between cardiac and gastric
      vagal activity. Due to the regionality of the ANS, different responses among
      different organ systems to the same stimulation (such as a meal) are quite
      possible. METHODS: In this study we monitored the postprandial changes of heart
      rate variability (HRV) and gastrointestinal (GI) hormones to determine whether
      both responded in a similar pattern. Twenty-two healthy volunteers (6 males and
      16 females) were enrolled. After recording a baseline ECG rhythm, further
      recordings were made at 20 min intervals for 120 min after a test meal. Serum
      human pancreatic polypeptide (PP), leptin, and total and active ghrelin levels
      were measured. KEY RESULTS: After the meal, HR increased significantly from
      baseline at each time point, except for 20 min after the meal. The high frequency
      (HF) power decreased significantly from 40 min to 120 min after the meal. In
      addition, the low frequency (LF) power also decreased significantly from 60 min
      to 120 min. However, the LF:HF ratio increased significantly from 20 min to 120
      min. There was a marked increase (>2 fold) of PP at 20 min after the meal, and
      the increase was sustained throughout the test period. CONCLUSIONS & INFERENCES:
      These findings suggest that HRV reflects cardiac, but not equivalently,
      abdominovagal activity. Therefore, HRV as an abdominovagal activity measurement
      in patients with GI functional problems should be used with caution, and other
      markers such as PP should be included.

PMID- 20059762
TI  - Non-peristaltic patterns of motor activity in the guinea-pig proximal colon.
AB  - BACKGROUND: The guinea-pig proximal colon contains semi-solid feces which are
      propelled by intermittent neural peristaltic waves to the distal colon, where
      solid pellets are formed. Between propulsive periods, complex motor patterns
      underlie fluid re-absorption and mixing of contents. METHODS: Spatio-temporal
      analysis of video recordings were used to investigate neural and myogenic
      patterns of non-peristaltic motor activity. KEY RESULTS: At low distension (6
      cmH(2)O), two major motor patterns were seen. Narrow rings of constriction
      (abrupt contractions) occurred at 19 cpm. These previously undescribed
      contractions occurred, almost simultaneously, at many points along the
      preparation, with a calculated propagation velocity of 110 mm s(-1). They were
      abolished by hexamethonium and by tetrodotoxin, indicating they were neurally
      mediated. Inhibition of nitric oxide synthase resulted in increased frequency of
      'abrupt contractions' suggesting ongoing inhibitory modulation by endogenous
      nitric oxide. After tetrodotoxin, another distinct motor pattern was revealed;
      'ripples'(1) consisted of shallow rings of contraction, occurring at 18 cpm and
      propagating at 2.7-2.9 mm s(-1) orally or aborally from multiple initiation
      sites. The frequency of 'ripples' increased as intraluminal pressure was raised,
      becoming very irregular at high distensions. L-type calcium channel blockers and
      openers affected the amplitude of 'ripples'. No frequency gradient of 'ripples'
      along the proximal colon was detected. This absence explains the multiple
      initiation sites which often shifted over time, and the oral and aboral
      propagation of 'ripples'. CONCLUSIONS & INFERENCES: The interaction of myogenic
      'ripples' with neurogenic 'abrupt contractions' generates localized alternating
      rings of contractions and dilatation, well suited to effective mixing of
      contents.

PMID- 20059763
TI  - Does Glycosylation as a modifier of Original Antigenic Sin explain the case age
      distribution and unusual toxicity in pandemic novel H1N1 influenza?
AB  - BACKGROUND: A pandemic novel H1N1 swine-origin influenza virus has emerged. Most
      recently the World Health Organization has announced that in a country-dependent
      fashion, up to 15% of cases may require hospitalization, often including
      respiratory support. It is now clear that healthy children and young adults are
      disproportionately affected, most unusually among those with severe respiratory
      disease without underlying conditions. One possible explanation for this case age
      distribution is the doctrine of Original Antigenic Sin, i.e., novel H1N1 may be
      antigenically similar to H1N1 viruses that circulated at an earlier time. Persons
      whose first exposure to influenza viruses was to such similar viruses would be
      relatively immune. However, this principle is not sufficient to explain the
      graded susceptibility between ages 20 and 60, the reduced susceptibility in
      children below age 10, and the unusual toxicity observed. METHODS: We collected
      case data from 11 countries, about 60% of all cases reported through mid-July
      2009. We compared sequence data for the hemagglutinin of novel H1N1 with
      sequences of H1N1 viruses from 1918 to the present. We searched for sequence
      differences that imply loss of antigenicity either directly through amino acid
      substitution or by the appearance of sites for potential glycosylation proximal
      to sites known to be antigenic in humans. We also considered T-cell epitopes.
      RESULTS: In our composite, over 75% of confirmed cases of novel H1N1 occurred in
      persons < or = 30 years old, with peak incidence in the age range 10-19 years.
      Less than 3% of cases occurred in persons over 65, with a gradation in incidence
      between ages 20 and 60 years.The sequence data indicates that novel H1N1 is most
      similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks
      glycosylation sites on the globular head of hemagglutinin (HA1) near antigenic
      regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that
      circulated until the early 1940s. Later H1N1 viruses progressively added new
      glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes
      were relatively unchanged. CONCLUSIONS: In this evolutionary context, Original
      Antigenic Sin exposure should produce an immune response increasingly mismatched
      to novel H1N1 in progressively younger persons. We suggest that it is this
      mismatch that produces both the gradation in susceptibility and the unusual
      toxicity. Several murine studies suggest specific cell types as a likely basis of
      the unusual toxicity. These studies also point to widely available pharmaceutical
      agents as plausible candidates for mitigating the toxic effects. The principle of
      Original Antigenic Sin modified by glycosylation appears to explain both the case
      age distribution and the unusual toxicity pattern of the novel H1N1 pandemic. In
      addition, it suggests pharmaceutical agents for immediate investigation for
      mitigation potential, and provides strategic guidance for the distribution of
      pandemic mitigation resources of all types.

PMID- 20059764
TI  - Analysis of the heat shock response in mouse liver reveals transcriptional
      dependence on the nuclear receptor peroxisome proliferator-activated receptor
      alpha (PPARalpha).
AB  - BACKGROUND: The nuclear receptor peroxisome proliferator-activated receptor alpha
      (PPARalpha) regulates responses to chemical or physical stress in part by
      altering expression of genes involved in proteome maintenance. Many of these
      genes are also transcriptionally regulated by heat shock (HS) through activation
      by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic
      level between PPARalpha and the HS response mediated by HSF1. RESULTS: Wild-type
      and PPARalpha-null mice were exposed to HS, the PPARalpha agonist WY-14,643 (WY),
      or both; gene and protein expression was examined in the livers of the mice 4 or
      24 hrs after HS. Gene expression profiling identified a number of Hsp family
      members that were altered similarly in both mouse strains. However, most of the
      targets of HS did not overlap between strains. A subset of genes was shown by
      microarray and RT-PCR to be regulated by HS in a PPARalpha-dependent manner. HS
      also down-regulated a large set of mitochondrial genes specifically in PPARalpha
      null mice that are known targets of PPARgamma co-activator-1 (PGC-1) family
      members. Pretreatment of PPARalpha-null mice with WY increased expression of PGC
      1beta and target genes and prevented the down-regulation of the mitochondrial
      genes by HS. A comparison of HS genes regulated in our dataset with those
      identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that
      although many HS genes are regulated independently of both PPARalpha and HSF1, a
      number require both factors for HS responsiveness. CONCLUSIONS: These findings
      demonstrate that the PPARalpha genotype has a dramatic effect on the
      transcriptional targets of HS and support an expanded role for PPARalpha in the
      regulation of proteome maintenance genes after exposure to diverse forms of
      environmental stress including HS.

PMID- 20059765
TI  - The cost of relapse and the predictors of relapse in the treatment of
      schizophrenia.
AB  - BACKGROUND: To assess the direct cost of relapse and the predictors of relapse
      during the treatment of patients with schizophrenia in the United States.
      METHODS: Data were drawn from a prospective, observational, noninterventional
      study of schizophrenia in the United States (US-SCAP) conducted between 7/1997
      and 9/2003. Patients with and without relapse in the prior 6 months were compared
      on total direct mental health costs and cost components in the following year
      using propensity score matching method. Baseline predictors of subsequent relapse
      were also assessed. RESULTS: Of 1,557 participants with eligible data, 310 (20%)
      relapsed during the 6 months prior to the 1-year study period. Costs for patients
      with prior relapse were about 3 times the costs for patients without prior
      relapse. Relapse was associated with higher costs for inpatient services as well
      as for outpatient services and medication. Patients with prior relapse were
      younger and had onset of illness at earlier ages, poorer medication adherence,
      more severe symptoms, a higher prevalence of substance use disorder, and worse
      functional status. Inpatient costs for patients with a relapse during both the
      prior 6 months and the follow-up year were 5 times the costs for patients with
      relapse during the follow-up year only. Prior relapse was a robust predictor of
      subsequent relapse, above and beyond information about patients' functioning and
      symptom levels. CONCLUSIONS: Despite the historical decline in utilization of
      psychiatric inpatient services, relapse remains an important predictor of
      subsequent relapse and treatment costs for persons with schizophrenia.

PMID- 20059766
TI  - A prospective evaluation of the safety and efficacy of the TAXUS Element
      paclitaxel-eluting coronary stent system for the treatment of de novo coronary
      artery lesions: design and statistical methods of the PERSEUS clinical program.
AB  - BACKGROUND: Paclitaxel-eluting stents decrease angiographic and clinical
      restenosis following percutaneous coronary intervention compared to bare metal
      stents. TAXUS Element is a third-generation paclitaxel-eluting stent which
      incorporates a novel, thinner-strut, platinum-enriched metal alloy platform. The
      stent is intended to have enhanced radiopacity and improved deliverability
      compared to other paclitaxel-eluting stents. The safety and efficacy of the TAXUS
      Element stent are being evaluated in the pivotal PERSEUS clinical trials.
      METHODS/DESIGN: The PERSEUS trials include two parallel studies of the TAXUS
      Element stent in single, de novo coronary atherosclerotic lesions. The PERSEUS
      Workhorse study is a prospective, randomized (3:1), single-blind, non-inferiority
      trial in subjects with lesion length < or = 28 mm and vessel diameter > or = 2.75
      mm to < or = 4.0 mm which compares TAXUS Element to the TAXUS Express2 paclitaxel
      eluting stent system. The Workhorse study employs a novel Bayesian statistical
      approach that uses prior information to limit the number of study subjects
      exposed to the investigational device and thus provide a safer and more efficient
      analysis of the TAXUS Element stent. PERSEUS Small Vessel is a prospective,
      single-arm, superiority trial in subjects with lesion length < or = 20 mm and
      vessel diameter > or = 2.25 mm to <2.75 mm that compares TAXUS Element with a
      matched historical bare metal Express stent control. DISCUSSION: The TAXUS
      PERSEUS clinical trial program uses a novel statistical approach to evaluate
      whether design and metal alloy iterations in the TAXUS Element stent platform
      provide comparable safety and improved procedural performance compared to the
      previous generation Express stent. PERSEUS trial enrollment is complete and
      primary endpoint data are expected in 2010. PERSEUS Workhorse and Small Vessel
      are registered at http://www.clinicaltrials.gov, identification numbers
      NCT00484315 and NCT00489541.

PMID- 20059767
TI  - Using targeted vouchers and health equity funds to improve access to skilled
      birth attendants for poor women: a case study in three rural health districts in
      Cambodia.
AB  - BACKGROUND: In many developing countries, the maternal mortality ratio remains
      high with huge poor-rich inequalities. Programmes aimed at improving maternal
      health and preventing maternal mortality often fail to reach poor women. Vouchers
      in health and Health Equity Funds (HEFs) constitute a financial mechanism to
      improve access to priority health services for the poor. We assess their
      effectiveness in improving access to skilled birth attendants for poor women in
      three rural health districts in Cambodia and draw lessons for further improvement
      and scaling-up. METHODS: Data on utilisation of voucher and HEF schemes and on
      deliveries in public health facilities between 2006 and 2008 were extracted from
      the available database, reports and the routine health information system.
      Qualitative data were collected through focus group discussions and key informant
      interviews. We examined the trend of facility deliveries between 2006 and 2008 in
      the three health districts and compared this with the situation in other rural
      districts without voucher and HEF schemes. An operational analysis of the voucher
      scheme was carried out to assess its effectiveness at different stages of
      operation. RESULTS: Facility deliveries increased sharply from 16.3% of the
      expected number of births in 2006 to 44.9% in 2008 after the introduction of
      voucher and HEF schemes, not only for voucher and HEF beneficiaries, but also for
      self-paid deliveries. The increase was much more substantial than in comparable
      districts lacking voucher and HEF schemes. In 2008, voucher and HEF beneficiaries
      accounted for 40.6% of the expected number of births among the poor. We also
      outline several limitations of the voucher scheme. CONCLUSIONS: Vouchers plus
      HEFs, if carefully designed and implemented, have a strong potential for reducing
      financial barriers and hence improving access to skilled birth attendants for
      poor women. To achieve their full potential, vouchers and HEFs require other
      interventions to ensure the supply of sufficient quality maternity services and
      to address other non-financial barriers to demand. If these conditions are met,
      voucher and HEF schemes can be further scaled up under close monitoring and
      evaluation.

PMID- 20059768
TI  - Does quality of life among breast cancer survivors one year after diagnosis
      differ depending on urban and non-urban residence? A comparative study.
AB  - BACKGROUND: This study examined the quality of life (QOL), measured by the
      Functional Assessment of Cancer Therapy (FACT) questionnaire, among urban (n =
      277) and non-urban (n = 323) breast cancer survivors and women from the general
      population (n = 1140) in Queensland, Australia. METHODS: Population-based samples
      of breast cancer survivors aged < 75 years who were 12 months post-diagnosis and
      similarly-aged women from the general population were recruited between 2002 and
      2007. RESULTS: Age-adjusted QOL among urban and non-urban breast cancer survivors
      was similar, although QOL related to breast cancer concerns was the weakest
      domain and was lower among non-urban survivors than their urban counterparts
      (36.8 versus 40.4, P < 0.01). Irrespective of residence, breast cancer survivors,
      on average, reported comparable scores on most QOL scales as their general
      population peers, although physical well-being was significantly lower among non
      urban survivors (versus the general population, P < 0.01). Overall, around 20%
      33% of survivors experienced lower QOL than peers without the disease. The odds
      of reporting QOL below normative levels were increased more than two-fold for
      those who experienced complications following surgery, reported upper-body
      problems, had higher perceived stress levels and/or a poor perception of handling
      stress (P < 0.01 for all). CONCLUSIONS: Results can be used to identify subgroups
      of women at risk of low QOL and to inform components of tailored recovery
      interventions to optimize QOL for these women following cancer treatment.

PMID- 20059769
TI  - Predictive value of progression-related gene classifier in primary non-muscle
      invasive bladder cancer.
AB  - BACKGROUND: While several molecular markers of bladder cancer prognosis have been
      identified, the limited value of current prognostic markers has created the need
      for new molecular indicators of bladder cancer outcomes. The aim of this study
      was to identify genetic signatures associated with disease prognosis in bladder
      cancer. RESULTS: We used 272 primary bladder cancer specimens for microarray
      analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR)
      analysis. Microarray gene expression analysis of randomly selected 165 primary
      bladder cancer specimens as an original cohort was carried out. Risk scores were
      applied to stratify prognosis-related gene classifiers. Prognosis-related gene
      classifiers were individually analyzed with tumor invasiveness (non-muscle
      invasive bladder cancer [NMIBC] and muscle invasive bladder cancer [MIBC]) and
      prognosis. We validated selected gene classifiers using RT-PCR in the original
      (165) and independent (107) cohorts. Ninety-seven genes related to disease
      progression among NMIBC patients were identified by microarray data analysis.
      Eight genes, a progression-related gene classifier in NMIBC, were selected for RT
      PCR. The progression-related gene classifier in patients with NMIBC was closely
      correlated with progression in both original and independent cohorts.
      Furthermore, no patient with NMIBC in the good-prognosis signature group
      experienced cancer progression. CONCLUSIONS: We identified progression-related
      gene classifier that has strong predictive value for determining disease outcome
      in NMIBC. This gene classifier could assist in selecting NMIBC patients who might
      benefit from more aggressive therapeutic intervention or surveillance.

PMID- 20059770
TI  - Mechanism of attenuation of leptin signaling under chronic ligand stimulation.
AB  - BACKGROUND: Leptin is an adipocyte-derived hormone that acts via its hypothalamic
      receptor (LEPRb) to regulate energy balance. A downstream effect essential for
      the weight-regulatory action of leptin is the phosphorylation and activation of
      the latent transcription factor STAT3 by LEPRb-associated Janus kinases (JAKs).
      Obesity is typically associated with chronically elevated leptin levels and a
      decreased ability of LEPRb to activate intracellular signal transduction pathways
      (leptin resistance). Here we have studied the roles of the intracellular tyrosine
      residues in the negative feedback regulation of LEPRb-signaling under chronic
      leptin stimulation. RESULTS: Mutational analysis showed that the presence of
      either Tyr985 and Tyr1077 in the intracellular domain of LEPRb was sufficient for
      the attenuation of STAT3 phosphorylation, whereas mutation of both tyrosines
      rendered LEPRb resistant to feedback regulation. Overexpression and RNA
      interference-mediated downregulation of suppressor of cytokine signaling 3
      (SOCS3) revealed that both Tyr985 and Tyr1077 were capable of supporting the
      negative modulatory effect of SOCS3 in reporter gene assays. In contrast, the
      inhibitory effect of SOCS1 was enhanced by the presence of Tyr985 but not
      Tyr1077. Finally, the reduction of the STAT-phosphorylating activity of the LEPRb
      complex after 2 h of leptin stimulation was not accompanied by the
      dephosphorylation or degradation of LEPRb or the receptor-associated JAK
      molecule, but depended on Tyr985 and/or Tyr1077. CONCLUSIONS: Both Tyr985 and
      Tyr1077 contribute to the negative regulation of LEPRb signaling. The inhibitory
      effects of SOCS1 and SOCS3 differ in the dependence on the tyrosine residues in
      the intracellular domain of LEPRb.

PMID- 20059771
TI  - Glutamate, aspartate and nucleotide transporters in the SLC17 family form four
      main phylogenetic clusters: evolution and tissue expression.
AB  - BACKGROUND: The SLC17 family of transporters transports the amino acids:
      glutamate and aspartate, and, as shown recently, also nucleotides. Vesicular
      glutamate transporters are found in distinct species, such as C. elegans, but the
      evolutionary origin of most of the genes in this family has been obscure.
      RESULTS: Our phylogenetic analysis shows that the SLC17 family consists of four
      main phylogenetic clades which were all present before the divergence of the
      insect lineage. One of these clades has not been previously described and it is
      not found in vertebrates. The clade containing Slc17a9 had the most restricted
      evolutionary history with only one member in most species. We detected expression
      of Slc17a1-17a4 only in the peripheral tissues but not in the CNS, while Slc17a5-
      Slc17a9 are highly expressed in both the CNS and periphery. CONCLUSIONS: The in
      situ hybridization studies on vesicular nucleotide transporter revealed high
      expression throughout the cerebral cortex, certain areas in the hippocampus and
      in specific nuclei of the hypothalamus and thalamus. Some of the regions with
      high expression, such as the medial habenula and the dentate gyrus of the
      hippocampus, are important sites for purinergic neurotransmission. Noteworthy,
      other areas relying on purine-mediated signaling, such as the molecular layer of
      the dentate gyrus and the periaqueductal gray, lack or have a very low expression
      of Slc17a9, suggesting that there could be another nucleotide transporter in
      these regions.

PMID- 20059773
TI  - Is hospital discharge administrative data an appropriate source of information
      for cancer registries purposes? Some insights from four Spanish registries.
AB  - BACKGROUND: The use of hospital discharge administrative data (HDAD) has been
      recommended for automating, improving, even substituting, population-based cancer
      registries. The frequency of false positive and false negative cases recommends
      local validation. METHODS: The aim of this study was to detect newly diagnosed,
      false positive and false negative cases of cancer from hospital discharge claims,
      using four Spanish population-based cancer registries as the gold standard.
      Prostate cancer was used as a case study. RESULTS: A total of 2286 incident cases
      of prostate cancer registered in 2000 were used for validation. In the most
      sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity
      ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most
      predictive algorithm (that using five diagnostic and five surgical codes)
      Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3%
      (CI95% 67.0-80.6). The most frequent reason for false positive cases was the
      number of prevalent cases inadequately considered as newly diagnosed cancers,
      ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for
      false negative cases was related to the number of cases not attended in hospital
      settings. In this case, figures ranged from 34.4% to 69.7% of false negative
      cases, in the most predictive algorithm. CONCLUSIONS: HDAD might be a helpful
      tool for cancer registries to reach their goals. The findings suggest that, for
      automating cancer registries, algorithms combining diagnoses and procedures are
      the best option. However, for cancer surveillance purposes, in those cancers like
      prostate cancer in which care is not only hospital-based, combining inpatient and
      outpatient information will be required.

PMID- 20059772
TI  - Comparative transcriptomic analysis of follicle-enclosed oocyte maturational and
      developmental competence acquisition in two non-mammalian vertebrates.
AB  - BACKGROUND: In vertebrates, late oogenesis is a key period during which the
      oocyte acquires its ability to resume meiosis (i.e. maturational competence) and
      to develop, once fertilized, into a normal embryo (i.e. developmental
      competence). However, the molecular mechanisms involved in these key biological
      processes are far from being fully understood. In order to identify key
      mechanisms conserved among teleosts and amphibians, we performed a comparative
      analysis using ovarian tissue sampled at successive steps of the maturational
      competence acquisition process in the rainbow trout (Oncorhynchus mykiss) and in
      the clawed toad (Xenopus laevis). Our study aimed at identifying common
      differentially expressed genes during late oogenesis in both species. Using an
      existing transcriptomic analysis that had previously been carried out in rainbow
      trout, candidate genes were selected for subsequent quantitative PCR-based
      comparative analysis. RESULTS: Among the 1200 differentially expressed clones in
      rainbow trout, twenty-six candidate genes were selected for further analysis by
      real-time PCR in both species during late oogenesis. Among these genes, eight had
      similar expression profiles in trout and Xenopus. Six genes were down-regulated
      during oocyte maturation (cyp19a1, cyp17a1, tescalcin, tfr1, cmah, hsd11b3) while
      two genes exhibited an opposite pattern (apoc1, star). In order to document
      possibly conserved molecular mechanisms, four genes (star, cyp19a1, cyp17a1 and
      hsd11b3) were further studied due to their known or suspected role in
      steroidogenesis after characterization of the orthology relationships between
      rainbow trout and Xenopus genes. Apoc1 was also selected for further analysis
      because of its reported function in cholesterol transport, which may modulate
      steroidogenesis by regulating cholesterol bioavailability in the steroidogenic
      cells. CONCLUSIONS: We have successfully identified orthologous genes exhibiting
      conserved expression profiles in the ovarian follicle during late oogenesis in
      both trout and Xenopus. While some identified genes were previously
      uncharacterized during Xenopus late oogenesis, the nature of these genes has
      pointed out molecular mechanisms possibly conserved in amphibians and teleosts.
      It should also be stressed that in addition to the already suspected importance
      of steroidogenesis in maturational competence acquisition, our approach has shed
      light on other regulatory pathways which may be involved in maturational and
      developmental competence acquisitions that will require further studies.

PMID- 20059775
TI  - A cost-utility analysis of psychoanalysis versus psychoanalytic psychotherapy.
AB  - OBJECTIVES: Despite the considerable and growing body of research about the
      clinical effectiveness of long-term psychoanalytic treatment, relatively little
      attention has been paid to economic evaluations, particularly with reference to
      the broader range of societal effects. In this cost-utility study, we examined
      the incremental cost-effectiveness ratio (ICER) of psychoanalysis versus
      psychoanalytic psychotherapy. METHODS: Incremental costs and effects were
      estimated by means of cross-sectional measurements in a cohort design
      (psychoanalysis, n = 78; psychoanalytic psychotherapy, n = 104). Quality-adjusted
      life-years (QALYs) were estimated for each treatment strategy using the SF-6D.
      Total costs were calculated from a societal perspective (treatment costs plus
      other societal costs) and discounted at 4 percent. Psychoanalysis was more costly
      than psychoanalytic psychotherapy, but also more effective from a health-related
      quality of life perspective. The ICER--that is, the extra costs to gain one
      additional QALY by delivering psychoanalysis instead of psychoanalytic
      psychotherapy--was estimated at 52,384 euros per QALY gained. CONCLUSIONS: Our
      findings show that the cost-utility ratio of psychoanalysis relative to
      psychoanalytic psychotherapy is within an acceptable range. More research is
      needed to find out whether cost-utility ratios vary with different types of
      patients. We also encourage cost-utility analyses comparing psychoanalytic
      treatment to other forms of (long-term) treatment.

PMID- 20059776
TI  - Cost-utility of a cardiovascular prevention program in highly educated adults:
      intermediate results of a randomized controlled trial.
AB  - OBJECTIVES: Little is known about the costs and the effects of cardiovascular
      prevention programs targeted at medical and behavioral risk factors. The aim was
      to evaluate the cost-utility of a cardiovascular prevention program in a general
      sample of highly educated adults after 1 year of intervention. METHODS: The
      participants were randomly assigned to intervention (n = 208) and usual care
      conditions (n = 106). The intervention consisted of medical interventions and
      optional behavior-change interventions (e.g., a tailored Web site). Cost data
      were registered from a healthcare perspective, and questionnaires were used to
      determine effectiveness (e.g., quality-adjusted life-years [QALYs]). A cost
      utility analysis and sensitivity analyses using bootstrapping were performed on
      the intermediate results. RESULTS: When adjusting for baseline utility
      differences, the incremental cost was 433 euros and the incremental effectiveness
      was 0.016 QALYs. The incremental cost-effectiveness ratio was 26,910 euros per
      QALY. CONCLUSIONS: The intervention was cost-effective compared with usual care
      in this sample of highly educated adults after 1 year of intervention. Increased
      participation would make this intervention highly cost-effective.

PMID- 20059777
TI  - Willingness to pay for allergy-vaccination among Danish patients with respiratory
      allergy.
AB  - OBJECTIVE: The aim of this study was to elicit willingness to pay (WTP) for
      allergen-specific subcutaneous injection immunotherapy (SCIT) in a cohort of
      respondents suffering from allergic-rhinoconjunctivitis (a-RC)/asthma, and to
      investigate how patients self-select to SCIT according to need. METHODS: A random
      sample of the general population was screened for a-RC/asthma and asked if they
      were willing to consider SCIT. They were asked to state their WTP for SCIT by way
      of a discrete choice question (DC-q), an open-ended WTP question (o-WTP-q), and
      questions relating to their sociodemographic background and the severity of their
      a-RC/asthma. The characteristics of respondents demanding SCIT were compared with
      the characteristics of respondents who have actually received SCIT to establish
      possible barriers to demand. RESULTS: Our results suggest that respondents do
      well in self-selecting themselves to SCIT on the basis of need according to
      disease burden measured in terms of a-RC classification, number of contacts with
      a general practitioner, number of sick days, and potential quality-adjusted life
      year loss. Mean WTP for SCIT was estimated at 655 euros (median, 267 euros) (o
      WTP-q) and 903 euros (95 percent confidence limit, 348-1,459) (DC-q). CONCLUSION:
      Characteristics of respondents, who consider SCIT and are willing to pay for
      SCIT, suggest that allergy sufferers select themselves appropriately according to
      need and not according to other characteristics, such as income or education.
      There is a significant discrepancy between those who hypothetically consider SCIT
      and those demanding SCIT in real life. This study suggests that there are
      barriers to entry related to age and education, but not to income.

PMID- 20059778
TI  - Prognostic value, clinical effectiveness, and cost-effectiveness of high
      sensitivity C-reactive protein as a marker for major cardiac events in
      asymptomatic individuals: a health technology assessment report.
AB  - OBJECTIVES: The aim of this study was to compare the predictive value, clinical
      effectiveness, and cost-effectiveness of high-sensitivity C-reactive protein (hs
      CRP)-screening in addition to traditional risk factor screening in apparently
      healthy persons as a means of preventing coronary artery disease. METHODS AND
      RESULTS: The systematic review was performed according to internationally
      recognized methods. Seven studies on risk prediction, one clinical decision
      analytic modeling study, and three decision-analytic cost-effectiveness studies
      were included. The adjusted relative risk of high hs-CRP-level ranged from 0.7 to
      2.47 (p < .05 in four of seven studies). Adding hs-CRP to the prediction models
      increased the areas under the curve by 0.00 to 0.027. Based on the clinical
      decision analysis, both individuals with elevated hs-CRP-levels and those with
      hyperlipidemia have a similar gain in life expectancy following statin therapy.
      One high-quality economic modeling study suggests favorable incremental cost
      effectiveness ratios for persons with elevated hs-CRP and higher risk. However,
      many model parameters were based on limited evidence. CONCLUSIONS: Adding hs-CRP
      to traditional risk factors improves risk prediction, but the clinical relevance
      and cost-effectiveness of this improvement remain unclear.

PMID- 20059779
TI  - Cost-effectiveness of screening for colorectal cancer in France using a guaiac
      test versus an immunochemical test.
AB  - OBJECTIVES: The aim of this study was to compare the cost and the effectiveness
      of two biennial fecal occult blood screening tests for colorectal cancer: a
      guaiac nonrehydrated test (G-FOBT) and an immunochemical test (I-FOBT) with the
      absence of screening. METHODS: A Markov model was developed to compare these
      strategies in a general population of subjects aged 50 to 74 over a 20-year
      period. RESULTS: Compared with the absence of screening, G-FOBT and I-FOBT were
      associated with a decrease in colorectal cancer mortality of 17.4 percent and
      25.2 percent, respectively. With regard to cost-effectiveness, expressed as cost
      per life-year gained, I-FOBT was the most effective and most costly alternative.
      Compared with no screening, G-FOBT and I-FOBT presented similar discounted
      incremental cost-effectiveness ratios: 2,739 euros and 2,819 euros respectively
      per life-year gained. When compared with G-FOBT, I-FOBT presented an incremental
      cost-effectiveness ratio of 2,988 euros per life-year gained. Sensitivity
      analyses showed the strong influence of the I-FOBT lead time, of the
      participation rate to screening for I-FOBT, and of the purchase price of the I
      FOBT on the discounted incremental cost-effectiveness ratios. CONCLUSIONS:
      Compared with the absence of screening and with G-FOBT, the biennial two-stool
      immunochemical test can be considered a promising method for mass screening for
      colorectal cancer.

PMID- 20059780
TI  - Cost-effectiveness analysis of the optimal threshold of an automated
      immunochemical test for colorectal cancer screening: performances of
      immunochemical colorectal cancer screening.
AB  - BACKGROUND: Most industrialized countries, including France, have undertaken to
      generalize colorectal cancer screening using guaiac fecal occult blood tests (G
      FOBT). However, recent researches demonstrate that immunochemical fecal occult
      blood tests (I-FOBT) are more effective than G-FOBT. Moreover, new generation I
      FOBT benefits from a quantitative reading technique allowing the positivity
      threshold to be chosen, hence offering the best balance between effectiveness and
      cost. We aimed at comparing the cost and the clinical performance of one round of
      screening using I-FOBT at different positivity thresholds to those obtained with
      G-FOBT to determine the optimal cut-off for I-FOBT. METHODS: Data were derived
      from an experiment conducted from June 2004 to December 2005 in Calvados (France)
      where 20,322 inhabitants aged 50-74 years performed both I-FOBT and G-FOBT.
      Clinical performance was assessed by the number of advanced tumors screened,
      including large adenomas and cancers. Costs were assessed by the French Social
      Security Board and included only direct costs. RESULTS: Screening using I-FOBT
      resulted in better health outcomes and lower costs than screening using G-FOBT
      for thresholds comprised between 75 and 93 ng/ml. I-FOBT at 55 ng/ml also offers
      a satisfactory alternative to G-FOBT, because it is 1.8-fold more effective than
      G-FOBT, without increasing the number of unnecessary colonoscopies, and at an
      extra cost of 2,519 euros per advanced tumor screened. CONCLUSIONS: The use of an
      automated I-FOBT at 75 ng/ml would guarantee more efficient screening than
      currently used G-FOBT. Health authorities in industrialized countries should
      consider the replacement of G-FOBT by an automated I-FOBT test in the near
      future.

PMID- 20059781
TI  - Cost-effectiveness of real-world infliximab use in patients with rheumatoid
      arthritis in Sweden.
AB  - OBJECTIVES: The objective of this study was to estimate the cost-effectiveness of
      infliximab use in patients with rheumatoid arthritis (RA) in Swedish clinical
      practice, based on patient-level data from the Stockholm TNF-alpha follow-up
      registry (STURE). METHODS: Real-world patient-level data on infliximab use from
      the STURE registry were implemented in a Markov cohort model, in which health
      states of functional status were classified according to the Health Assessment
      Questionnaire Disability Index (HAQ-five categories) and twenty-eight joint count
      Disease Activity Score (DAS28). The transition probabilities between HAQ and
      DAS28 states during treatment, as well as discontinuation rates were modeled
      based on data from the registry for patients using infliximab as their first-line
      biological treatment. The transition probabilities in the comparator arm, that
      is, disease progression without biologic treatment, as well as mortality rates,
      costs, and utilities were based on published literature. The analysis had a
      societal cost perspective. RESULTS: Infliximab was associated with an incremental
      gain in quality-adjusted life-years of 1.02 and an incremental cost of 23,264
      euros per patient compared with progression without biologic treatment, producing
      an incremental cost-effectiveness ratio (ICER) of 22,830 euros (SEK211,136 or
      US$31,230). Sensitivity analyses of input parameters and model assumptions
      produced ICERs in the range from 18,000 euros to 47,000 euros. CONCLUSIONS:
      Results from base-case and sensitivity analyses fell well below established
      benchmarks for cost-effectiveness in Sweden. The results, therefore, indicated
      that infliximab treatment for RA has provided good societal value for money in
      Swedish clinical practice, compared with a scenario of no biological treatment.

PMID- 20059782
TI  - Cost-effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II
      receptor blockers in newly diagnosed type 2 diabetes in Germany.
AB  - OBJECTIVES: Type 2 diabetes is the main cause of end-stage renal disease in
      Europe and the United States. Angiotensin-converting enzyme (ACE) inhibitors slow
      down the progression of renal disease and, therefore, provide a renal-protective
      effect. The aim of this study was to assess the most cost-effective time to start
      an ACE inhibitor (or an angiotensin II receptor blocker in the event of cough) in
      patients with type 2 diabetes in Germany. METHODS: Three strategies were
      compared: treating all patients at the time of diagnosing type 2 diabetes,
      screening for microalbuminuria, and screening for macroalbuminuria. A lifetime
      Markov decision model with simulated 50-year-old patients with newly diagnosed
      diabetes mellitus was developed using published data on costs and health outcomes
      and simulating the progression of renal disease. A statutory health insurance
      perspective was adopted. RESULTS: In the base-case analysis, the treat-all
      strategy is associated with the lowest costs and highest benefit and, therefore,
      dominates screening both for macroalbuminuria and microalbuminuria. A
      multivariate sensitivity analysis shows that the probability of savings is 89
      percent. CONCLUSIONS: Patients with type 2 diabetes should receive an ACE
      inhibitor immediately after diagnosis if they do not have contraindications. The
      potential for cost savings would be even larger if the prevention of
      cardiovascular events were considered.

PMID- 20059783
TI  - Are Key Principles for improved health technology assessment supported and used
      by health technology assessment organizations?
AB  - Previously, our group-the International Working Group for HTA Advancement
      proposed a set of fifteen Key Principles that could be applied to health
      technology assessment (HTA) programs in different jurisdictions and across a
      range of organizations and perspectives. In this commentary, we investigate the
      extent to which these principles are supported and used by fourteen selected HTA
      organizations worldwide. We find that some principles are broadly supported:
      examples include being explicit about HTA goals and scope; considering a wide
      range of evidence and outcomes; and being unbiased and transparent. Other
      principles receive less widespread support: examples are addressing issues of
      generalizability and transferability; being transparent on the link between HTA
      findings and decision-making processes; considering a full societal perspective;
      and monitoring the implementation of HTA findings. The analysis also suggests a
      lack of consensus in the field about some principles--for example, considering a
      societal perspective. Our study highlights differences in the uptake of key
      principles for HTA and indicates considerable room for improvement for HTA
      organizations to adopt principles identified to reflect good HTA practices. Most
      HTA organizations espouse certain general concepts of good practice--for example,
      assessments should be unbiased and transparent. However, principles that require
      more intensive follow-up--for example, monitoring the implementation of HTA
      findings--have received little support and execution.

PMID- 20059784
TI  - Coverage with Evidence Development: applications and issues.
AB  - OBJECTIVES: The aim of this study was to describe the current issues surrounding
      Coverage with Evidence Development (CED). CED is characterized by restricted
      coverage for a new technology in parallel with targeted research when the stated
      goal of the research or data collection is to provide definitive evidence for the
      clinical or cost-effectiveness impact of the new technology. METHODS: Presented
      here is information summarized and interpreted from presentations and discussions
      at the 2008 Health Technology Assessment International (HTAi) meeting and
      additional information from the medical literature. This study describes the
      differences between CED and other conditional coverage agreements, provides a
      brief history of CED, describes real-world examples of CED, describes the areas
      of consensus between the stakeholders, discusses the areas for future negotiation
      between stakeholders, and proposes criteria to assist stakeholders in determining
      when CED could be appropriate. RESULTS: Payers could interpret the evidence
      obtained from a CED program either positively or negatively, and a range of
      possible changes to the reimbursement status of the new technology may result.
      Striking an appropriate balance between the demands for prompt access to new
      technology and acknowledging that some degree of uncertainty will always exist is
      a critical challenge to the uptake of this innovative form of conditional
      coverage. CONCLUSIONS: When used selectively for innovative procedures,
      pharmaceuticals, or devices in the appropriate disease areas, CED may provide
      patients access to promising medicines or technologies while data to minimize
      uncertainty are collected.

PMID- 20059785
TI  - Using clinical databases to evaluate healthcare interventions.
AB  - OBJECTIVES: The aim of this study was to test the feasibility of conducting
      rigorous, nonrandomized studies (NRSs) of healthcare interventions using existing
      clinical databases in terms of the following: recruiting a large representative
      sample of hospitals, identifying eligible cases, matching cases to controls to
      achieve similar baseline characteristics, making meaningful comparisons of
      outcomes, and carrying out subgroup analyses. METHODS: Data were extracted from
      the Intensive Care National Audit & Research Centre's Case Mix Programme Database
      to investigate the impact of management with a pulmonary artery catheter (PAC) in
      intensive care unit (ICU) patients. Participating ICUs were invited to collect
      additional data for the analysis. Patients managed with a PAC were matched to
      control patients on their propensity score. Hospital mortality was then compared
      between the two groups. RESULTS: Of 117 eligible ICUs, 68 (58 percent) agreed to
      participate, of which 57 (84 percent) collected additional data. Although a
      slightly higher proportion of larger ICUs in university hospitals participated,
      the patient case-mix was similar to that in nonparticipating ICUs. Almost all
      patients managed with a PAC (98 percent) were successfully matched to patients
      managed without a PAC. The two groups were similar for baseline characteristics.
      However, hospital mortality was worse for PAC patients than for non-PAC patients
      (odds ratio, 1.28; 95 percent confidence interval, 1.06-1.55). Subgroup analysis
      suggested that the impact of management with a PAC was modified by severity of
      illness. CONCLUSIONS: Rigorous NRSs are feasible if they are based on data from
      high-quality clinical databases. However, the reliability of estimated treatment
      effects from such studies requires further investigation.

PMID- 20059786
TI  - Usefulness of a short-term register for health technology assessment where the
      evidence base is poor.
AB  - This study reviews the coverage and usefulness of a short-term register,
      established specifically for health technology assessment of a novel
      interventional procedure (minimally invasive repair of pectus excavatum, or the
      Nuss procedure). METHODS: Coverage of the register during 2004-07 was assessed by
      comparison with Hospital Episodes Statistics (HES) for England. Its usefulness
      was assessed by comparing safety and efficacy data with the published literature
      and by feedback from committee members who in 2009 were involved in reviewing
      NICE's original guidance from 2003. RESULTS: The register reported 260 cases from
      thirteen UK hospitals during nearly 9 years. During a coverage evaluation period
      of 3 years, there were 152 registered Nuss procedures. An additional 246 repairs
      of pectus excavatum were undertaken in twenty-six previously unidentified
      hospitals. Of the 246, 23 were Nuss procedures (from two hospitals), 140 were
      open procedures (from eleven hospitals), and 3 were coding errors. No details
      were available for eighty cases undertaken at ten hospitals. The quantity of
      published literature had increased substantially since publication of original
      guidance in 2003. It related mostly to technical and safety outcomes, whereas the
      register included patient reported outcomes. The literature and the register
      reported similar rates of major adverse events such as bar displacement (2-10
      percent). Committee members considered that the Register made a useful
      contribution to guidance development. CONCLUSIONS: This study shows that a
      register set up to support a health technology assessment process can produce
      useful data both about safety and about patient-reported outcomes. Coverage may
      be improved by active follow-up based on routine hospital statistics. Improvement
      in coding for new procedures is needed in the United Kingdom.

PMID- 20059787
TI  - Comparison of the assessment of five new interventional procedures in different
      countries.
AB  - OBJECTIVES: The aim of this study was to identify and compare health technology
      assessments of the same new interventional procedures produced in different
      countries. METHODS: We selected five new interventional procedures and studied
      related assessments produced in different countries. RESULTS: There were twenty
      assessments (range, 3-5 per procedure) from nine countries--fourteen from
      Australia, Canada, and United Kingdom. The number of primary RCTs cited by the
      assessments ranged from 0 to 13. In the assessment reports, "headline" statements
      about the strength of evidence for efficacy (73 percent) were made more
      frequently than for safety (53 percent). These statements were scored for their
      apparent judgment of the strength of the evidence--1 (poor) to 5 (strong)--and
      received scores of 3 or less in all but four cases. Recommendations about
      additional research were included in 55 percent of the assessments. Statements in
      assessments about other aspects of use of the procedures were included more
      infrequently--in 35 percent for patient selection, in 20 percent for consent
      issues, and in 15 percent for types of clinical teams. Recommendations about
      appropriate healthcare settings, or about operator training, were included only
      in assessments produced by a single organization. CONCLUSION: There was a only
      small number of assessments world-wide, for a range of new procedures with
      potentially high impact. Where available, assessments were produced on a
      relatively poor evidence base. International collaboration in evidence appraisal
      and review, and in the gathering of new data through research or registers, could
      improve the advice available to healthcare systems worldwide about the adoption
      of new interventional procedures.

PMID- 20059788
TI  - Time to full publication of studies of anticancer drugs for breast cancer, and
      the potential for publication bias.
AB  - OBJECTIVES: Nonpublication of results of clinical trials can contribute to
      inappropriate medical decisions. The primary aim of this systematic review was to
      investigate publication delays between conference abstracts and full journal
      publications from randomized controlled trial results of new anticancer agents
      for breast cancer. The review was restricted to anticancer agents previously, or
      due to be, appraised in the United Kingdom by the National Institute for Health
      and Clinical Excellence. A secondary objective was to identify whether there are
      any apparent biases in the publication and reporting of these trials. METHODS: We
      searched six electronic databases up to August 2007, including Medline and the
      Cochrane Library. Two reviewers independently selected studies, extracted and
      assessed the data. RESULTS: Six anticancer treatments were identified: docetaxel,
      paclitaxel, trastuzumab, gemcitabine, lapatinib, and bevacizumab. Of eighteen
      included trials, only four publications from three trials reported the same
      outcomes in both abstract and full publication. Time delays ranged from 5 to 19
      months. Eleven trial abstracts were still without a full publication at the end
      of our searches, varying from 3 to 38 months since abstract publication.
      Observational analysis revealed no particular publishing biases. CONCLUSIONS:
      Whereas delays in publication appear reasonable over a period of months, many
      were not published in full over a period of years and others would appear to be
      unlikely to ever be published. Further research should investigate the impact of
      publication delays on the availability of new drug treatments in clinical
      practice.

PMID- 20059789
TI  - Do the 15D scores and time trade-off (TTO) values of hospital patients' own
      health agree?
AB  - OBJECTIVES: The aim of this study was to estimate an empirical relationship and
      degree of agreement between the TTO values of patients' own health and their 15D
      scores. METHODS: A total of 863 hospital patients aged 18-93 years filled in the
      15D questionnaire to establish their 15D score and valued their present health
      with TTO. Wilcoxon signed rank test, the Spearman rank correlation coefficient
      and Tobit models were used to analyze the relation between the 15D and TTO
      scores. RESULTS: The null hypothesis of no tendency for one set of scores to be
      higher or lower than the other set could not be rejected. Apart from dummies for
      few patients groups, no additional information to the 15D score was found that
      would have explained significantly the variance in the TTO valuations of
      patients' own health. The agreement between these to sets of scores turned out
      quite good at the aggregate level. CONCLUSIONS: To the extent that mean TTO
      valuations of patients own health are valid for QALY calculations as they at
      least theoretically should be, and if experience of health states to be valued
      counts, the 15D scores are also valid without any transformation in a large group
      of heterogeneous patients. However, in certain patient groups, the agreement was
      not as good as overall.

PMID- 20059790
TI  - Relative effectiveness assessment of listed drugs (REAL): a new method for an
      early comparison of the effectiveness of approved health technologies.
AB  - OBJECTIVES: Post-listing assessment of pharmaceuticals depends on national
      habits. In England, the assessment is based on estimates of cost per quality
      adjusted life-year. These are made some considerable time after listing (negative
      list). In France, effectiveness, and then efficiency, is assessed immediately
      after listing (positive list). We propose a new formal method--the REAL method-
      that can help make early comparisons of the effectiveness of medical treatments.
      METHODS: Relative efficacies are first obtained from randomized controlled trials
      (RCTs). Members of the Transparency Committee (French National Authority for
      Health) are then consulted by questionnaire on the transposability of these
      results to real life. The RCT results and experts' ratings are entered into an
      effect model to obtain estimates of relative effectiveness, using unidimensional
      scaling, and bootstrap procedures. RESULTS: Application of the REAL method to the
      example of a new drug to treat Parkinson's disease and three comparators used in
      the same indication provided graphs of the distributions of their relative
      efficacy and relative effectiveness. The new drug was found to provide no added
      value. CONCLUSIONS: The REAL method is a rational, transparent, and practical
      procedure for comparing the effectiveness of pharmaceuticals in an immediate post
      listing setting.

PMID- 20059791
TI  - Can laryngectomees smell? Considerations regarding olfactory rehabilitation
      following total laryngectomy.
AB  - Total laryngectomy is performed for patients with advanced malignancy of the
      larynx and pharynx, and disconnects the nose and mouth from the lower respiratory
      tract. Rehabilitation of olfactory function in these patients is often neglected,
      despite recognition that anosmia and hyposmia are common and can readily be
      addressed. This paper reviews the literature concerning olfactory loss post
      laryngectomy, methods of olfactory rehabilitation, assessment of olfactory
      function and quality of life issues.

PMID- 20059792
TI  - Vocal function following discharge from intensive care.
AB  - INTRODUCTION: There is growing interest in the long term outcomes of critical
      care. The degree of vocal morbidity suffered by patients surviving intensive care
      admission has not previously been reported. OBJECTIVE: To determine the degree of
      subjective, patient-reported vocal morbidity following discharge from intensive
      care. MATERIALS AND METHODS: A prospective study was undertaken of patients
      admitted to intensive care. A total of 273 consecutive admissions were assessed;
      181 patients were suitable for inclusion. MAIN OUTCOME MEASURE: The Voice Symptom
      Scale questionnaire. RESULTS: Eighty-three patients responded. Twenty-seven
      patients (33 per cent) reported a degree of vocal morbidity greater than that
      suffered by patients treated for early laryngeal cancer. Thirteen patients (16
      per cent) reported a degree of morbidity greater than that suffered by patients
      attending voice clinics. CONCLUSION: Up to one-third of patients who survived
      admission to an intensive care unit reported suffering significant vocal
      morbidity. The Voice Symptom Scale could be used in an intensive care follow-up
      setting to identify and ensure the referral of such patients.

PMID- 20059793
TI  - Case report of Zenker's diverticulum in identical twins: further evidence for
      genetic predisposition.
AB  - OBJECTIVE: We report identical twins with Zenker's diverticulum. METHODS: Case
      report and literature review. CONCLUSIONS: Geographical and racial variation in
      occurrence, and rare familial cases, suggest that inherited factors play a role
      in the pathogenesis of Zenker's diverticulum. The identical twins reported here
      provide further evidence supporting a genetic predisposition.

PMID- 20059794
TI  - A computerised tailored intervention for increasing intakes of fruit, vegetables,
      brown bread and wholegrain cereals in adolescent girls.
AB  - OBJECTIVE: To evaluate the effectiveness of a computer-generated tailored
      intervention leaflet compared with a generic leaflet aimed at increasing brown
      bread, wholegrain cereal, fruit and vegetable intakes in adolescent girls.
      DESIGN: Clustered randomised controlled trial. Dietary intake was assessed via
      three 24 h dietary recalls. SETTING: Eight secondary schools in areas of low
      income and/or high ethnic diversity, five in London and three in the West
      Midlands, UK. SUBJECTS: Girls aged 12-16 years participated (n 823) and were
      randomised by school class to receive either the tailored intervention (n 406) or
      a generic leaflet (n 417). RESULTS: At follow-up 637 (77 %) participants
      completed both baseline and follow-up dietary recalls. The tailored intervention
      leaflet had a statistically significant effect on brown bread intake (increasing
      from 0.39 to 0.51 servings/d) with a smaller but significant increase in the
      control group also (increasing from 0.28 to 0.35 servings/d). The intervention
      group achieved 0.05 more servings of brown bread daily than the control group (P
      < 0.05), which is equivalent to 0.35 servings/week. For the other foods there
      were no significant effects of the tailored intervention. CONCLUSIONS: The
      intervention group consumed approximately 0.35 more servings of brown bread
      weekly than the control group from baseline. Although this change between groups
      was statistically significant the magnitude was small. Evaluation of the
      intervention was disappointing but the tailored leaflet was received more
      positively in some respects than the control leaflet. More needs to be done to
      increase motivation to change dietary intake in adolescent girls.

PMID- 20059795
TI  - Energy density, energy costs and income - how are they related?
AB  - OBJECTIVE: To examine the association between energy density and energy costs in
      single food items and composed diets, and to explore differences in energy
      density and energy cost between income levels. DESIGN: A cross-sectional study
      using data from two Dutch cohort studies and recent national food prices. Food
      prices were retrieved from two market leader supermarkets. Data on dietary intake
      were measured using a computerized face-to-face interview (cohort 1) and 24 h
      recalls (cohort 2). SETTING: The Netherlands. SUBJECTS: A sample of 373 young
      adults from the Amsterdam Growth and Health Longitudinal Study (AGHLS, measured
      in 2000) and a sample of 200 community-dwelling elderly from the Longitudinal
      Ageing Study Amsterdam (LASA, measured in 2007). RESULTS: We found significant
      inverse associations between energy density and energy costs in single food items
      (r = -0.436, P < 0.01) and composed diets (AGHLS men r = -0.505, women r = 
      0.413, P < 0.001; LASA men r = -0.559, women r = -0.562, P < 0.001). Furthermore,
      we found that people stratified into higher energy density quartiles consumed
      significantly more energy per day, less fruits and vegetables, and had
      significantly lower diet costs. Explorative analyses on income did not reveal
      significant differences regarding energy density, costs, or fruit and vegetable
      intake. CONCLUSIONS: In the Netherlands also, energy density was inversely
      related with energy costs, implying that healthier diets cost more. However, we
      could not find differences in energy density or costs between income levels.
      Future research, using precise food expenditures, is of main importance in
      studying the economics of obesity and in the aim of making the healthier choice
      easier.

PMID- 20059796
TI  - Flavonoid intake and disability-adjusted life years due to Alzheimer's and
      related dementias: a population-based study involving twenty-three developed
      countries.
AB  - OBJECTIVE: Dietary flavonoids and their metabolites may have neuroprotective
      effects against age-associated neurodegenerative disorders such as Alzheimer's
      and related dementias (dementia). There is a lack of population studies, however,
      on correlations between flavonoid intake and dementia. The main objective of the
      present study was to analyse such a relationship at a large-scale population
      level. DESIGN: Based on global data (FAO, WHO), databases were generated for: (i)
      flavonoid content of foods; (ii) per capita national dietary intakes of
      flavonoids and other dietary factors; and (iii) disability-adjusted life years -
      a measure of burden and death - due to dementia. Five major flavonoid subclasses
      were examined. To minimize influences due to accuracy and reliability of the
      disease source data, twenty-three developed countries were selected after
      statistical evaluation. RESULTS: Flavonols and combined flavonoids (all five
      combined) intakes were the only two parameters with significant (P < 0.05)
      negative dementia correlations. Multiple linear regression models confirmed this
      relationship, and excluded confounding from some other dietary and non-dietary
      factors. Similar analyses with non-dementia, neurological/psychiatric diseases
      did not yield significant correlations. CONCLUSIONS: At a global level, and in
      the context of different genetic backgrounds, our results suggest that higher
      consumption of dietary flavonoids, especially flavonols, is associated with lower
      population rates of dementia in these countries.

PMID- 20059797
TI  - Deconstructing major depression: a validation study of the DSM-IV symptomatic
      criteria.
AB  - BACKGROUND: The DSM-IV symptomatic criteria for major depression (MD) derive
      primarily from clinical experience with modest empirical support. METHOD: The
      sample studied included 1015 (518 males, 497 females) Caucasian twins from a
      population-based registry who met criteria for MD in the year prior to the
      interview. Logistic regression analyses were conducted to compare the
      associations of: (1) single symptomatic criterion, (2) two groups of criteria
      reflecting cognitive and neurovegetative symptoms, with a wide range of potential
      validators including demographic factors, risk for future episodes, risk of MD in
      the co-twin, characteristics of the depressive episode, the pattern of co
      morbidity and personality traits. RESULTS: The individual symptomatic criteria
      showed widely varying associations with the pattern of co-morbidity, personality
      traits, features of the depressive episode and demographic characteristics. When
      examined separately, these two criteria groups showed robust differences in their
      patterns of association, with the validators with the cognitive criteria
      generally producing stronger associations than the neurovegetative. CONCLUSIONS:
      Among depressed individuals, individual DSM-IV symptomatic criteria differ
      substantially in their predictive relationship with a range of clinical
      validators. These results challenge the equivalence assumption for the
      symptomatic criteria for MD and suggest a more than expected degree of 'covert'
      heterogeneity among these criteria. Part of this heterogeneity is captured by the
      distinction between cognitive versus neurovegetative symptoms, with cognitive
      symptoms being more strongly associated with most clinically relevant
      characteristics. Detailed psychometric evaluation of DSM-IV criteria is overdue.

PMID- 20059798
TI  - Deinstitutionalization revisited: a 5-year follow-up of a randomized clinical
      trial of hospital-based rehabilitation versus specialized assertive intervention
      (OPUS) versus standard treatment for patients with first-episode schizophrenia
      spectrum disorders.
AB  - BACKGROUND: The effects of hospital-based rehabilitation including weekly
      supportive psychodynamic therapy compared with specialized assertive intervention
      and standard treatment has not previously been investigated in first-episode
      psychosis. The aim of the study was to examine long-term effect on use of
      institutional care of different intensive interventions for patients with first
      episode schizophrenia spectrum disorder on use of psychiatric bed days and days
      in supported housing. METHOD: A total of 94 severely ill patients with first
      episode schizophrenia spectrum disorders were included in a special part of the
      Copenhagen OPUS trial and randomized to either the specialized assertive
      intervention program (OPUS), standard treatment or hospital-based rehabilitation.
      RESULTS: It was a stable pattern that patients randomized to hospital-based
      rehabilitation spent more days in psychiatric wards and in supported housing
      throughout the 5-year follow-up period compared with the two other groups.
      Patients in OPUS treatment spent significantly fewer days in psychiatric wards
      and supported housing in the first 3 years compared with patients in hospital
      based rehabilitation. Due to attrition and small sample size, differences in
      level of psychotic and negative symptoms at 5-year follow-up could not be
      evaluated. CONCLUSIONS: The study indicates that hospital-based rehabilitation
      together with weekly supportive psychodynamic therapy was associated with a
      continued increased use of psychiatric bed days and days in supported housing.
      The data cannot justify using hospital-based rehabilitation in first-episode
      psychosis.

PMID- 20059799
TI  - A prospective longitudinal study of the prevalence of post-traumatic stress
      disorder resulting from childbirth events.
AB  - BACKGROUND: Childbirth has been linked to postpartum impairment. However,
      controversy exists regarding the onset and prevalence of post-traumatic stress
      disorder (PTSD) after childbirth, with seminal studies being limited by
      methodological issues. This longitudinal prospective study examined the
      prevalence of PTSD following childbirth in a large sample while controlling for
      pre-existing PTSD and affective symptomatology. METHOD: Pregnant women in their
      third trimester were recruited over a 12-month period and interviewed to identify
      PTSD and anxiety and depressive symptoms during the last trimester of pregnancy,
      4-6 weeks postpartum, 12 weeks postpartum and 24 weeks postpartum. RESULTS: Of
      the 1067 women approached, 933 were recruited into the study. In total, 866 (93%)
      were retained to 4-6 weeks, 826 (89%) were retained to 12 weeks and 776 (83%)
      were retained to 24 weeks. Results indicated that, uncontrolled, 3.6% of women
      met PTSD criteria at 4-6 weeks postpartum, 6.3% at 12 weeks postpartum and 5.8%
      at 24 weeks postpartum. When controlling for PTSD and partial PTSD due to
      previous traumatic events as well as clinically significant anxiety and
      depression during pregnancy, PTSD rates were less at 1.2% at 4-6 weeks, 3.1% at
      12 weeks and 3.1% at 24 weeks postpartum. CONCLUSIONS: This is the first study to
      demonstrate the occurrence of full criteria PTSD resulting from childbirth after
      controlling for pre-existing PTSD and partial PTSD and clinically significant
      depression and anxiety in pregnancy. The findings indicate that PTSD can result
      from a traumatic birth experience, though this is not the normative response.

PMID- 20059800
TI  - Preliminary evidence that estradiol moderates genetic influences on disordered
      eating attitudes and behaviors during puberty.
AB  - BACKGROUND: Puberty moderates genetic influences on disordered eating attitudes
      and behaviors, with little genetic influence before puberty but large (50%)
      genetic effects during and after puberty. To date, however, nothing is known
      about the mechanisms that underlie these effects. Estradiol is a particularly
      promising candidate, as estrogens become elevated at puberty and regulate gene
      transcription within neurotransmitter systems important for eating-related
      phenotypes. The aim of this pilot study was to examine whether estradiol levels
      moderate genetic influences on disordered eating during puberty. METHOD:
      Participants included 198 female twins (ages 10-15 years) from the Michigan State
      University Twin Registry. Disordered eating attitudes and behaviors were assessed
      with the total score, weight preoccupation, body dissatisfaction and binge
      eating/compensatory behavior subscales of the Minnesota Eating Behavior Survey
      (MEBS). Afternoon saliva samples were assayed for estradiol levels. Moderation of
      genetic effects was examined by comparing twin correlations in low versus high
      estradiol groups. RESULTS: In the low estradiol group, monozygotic (MZ) and
      dizygotic (DZ) twin correlations for all MEBS scales were similar, suggesting
      little genetic influence. In the high estradiol group, the MZ twin correlation
      was more than double the DZ twin correlation, indicating the presence of genetic
      effects. Findings could not be accounted for by age, body mass index or the
      physical changes of puberty. CONCLUSIONS: Estradiol may be one important
      moderator of genetic effects on disordered eating during puberty. Larger twin
      studies are needed to replicate this pilot work and quantify the extent of
      genetic moderation.

PMID- 20059801
TI  - Longitudinal associations between post-traumatic distress and depressive symptoms
      following a traumatic event: a test of three models.
AB  - BACKGROUND: Symptoms of post-traumatic stress disorder (PTSD) and depression are
      highly co-morbid following a traumatic event. Nevertheless, decisive evidence
      regarding the direction of the relationship between these clinical entities is
      missing. METHOD: The aim of the present study was to examine the nature of this
      relationship by comparing a synchronous change model (PTSD and depression are
      time synchronous, possibly stemming from a third common factor) with a
      demoralization model (i.e. PTSD symptoms causing depression) and a depressogenic
      model (i.e. depressive symptoms causing PTSD symptoms). Israeli adult victims of
      single-event traumas (n=156) were assessed on measures of PTSD and depression at
      2, 4 and 12 weeks post-event. RESULTS: A cross-lagged structural equation
      modeling (SEM) analysis provided results consistent with the synchronous change
      model and the depressogenic model. CONCLUSIONS: Depressive symptoms may play an
      important role in the development of post-traumatic symptoms.

PMID- 20059802
TI  - Chronic antipsychotic treatment: protracted decreases in phospho-TrkA levels in
      the rat hippocampus.
AB  - There is growing evidence of neurotrophin alterations in neuropsychiatric
      illnesses such as schizophrenia and further, neurotransmitters known to be
      adversely affected in schizophrenia (e.g. dopamine) can activate neurotrophin
      signalling pathways via G protein-coupled receptors. However, it is unclear how
      the primary therapeutic agents used in schizophrenia affect neurotrophin
      signalling. This is important given that all currently prescribed antipsychotic
      drugs serve as ligands at dopamine receptors. In this study, chronic effects of
      representative conventional and second-generation antipsychotics on nerve growth
      factor (NGF) receptor levels were assessed in the rat. The results indicated no
      significant drug effects on TrkA levels in any brain region analysed; however,
      three of the five antipsychotics analysed significantly decreased phospho-TrkA
      (i.e. the activated form of the receptor) in the hippocampus. These data indicate
      that chronic antipsychotic treatment may result in deleterious effects on
      neurotrophin signalling in an important brain region for information processing
      and cognition.

PMID- 20059803
TI  - Antidepressant-like effects of an AMPA receptor potentiator under a chronic mild
      stress paradigm.
AB  - Enhancement of AMPA receptor (AMPAR) function has emerged as a novel strategy for
      treatment of depression. Nevertheless, studies on AMPAR function in chronic
      animal models used to predict antidepressant efficacy are surprisingly lacking.
      We investigated the role of AMPARs in antidepressant action in an unpredictable
      chronic mild stress (UCMS) model in BALB/c mice. After 3 wk of UCMS, BALB/c mice
      developed a number of depressive-like behaviours that were successfully prevented
      by fluoxetine (20 mg/kg) administration. The AMPAR potentiator LY392098 [N-2-(4
      (3-thienyl)phenyl)propyl 2-propanesulfonamide] (5 mg/kg), when administered
      alone, functioned like classic antidepressants by reducing weight loss, fur
      deterioration and immobility in the tail suspension test. However, LY392098 did
      not restore sucrose preference and did not reduce anxiety (marble-burying) in
      stressed mice. In the same protocol, the AMPAR antagonist GYKI (10 mg/kg)
      reversed most, but not all, of the antidepressant-like actions of fluoxetine.
      Thus, the antidepressant-like effects of LY392098 were fully predicted by the
      AMPAR dependence of effects demonstrated for fluoxetine. Our results demonstrate
      that, in the UCMS paradigm, AMPAR activation exhibits antidepressant-like
      activity that relates preferentially to specific depressive-like responses and
      that those specific responses can be defined by their regulation by AMPAR
      modulation under conditions of stress.

PMID- 20059804
TI  - Genetic and epigenetic influences on expression of spermine synthase and spermine
      oxidase in suicide completers.
AB  - Alterations in the levels of spermine synthase (SMS) and spermine oxidase (SMOX),
      two enzymes involved in polyamine metabolism, have previously been observed in
      brains of suicide completers. To characterize the roles played by genetic and
      epigenetic factors in determining expression levels of these genes, as well as to
      identify potential mechanisms by which to explain our findings in suicide
      completers, we (1) assessed the role of promoter polymorphisms in determining
      expression in the brain and in vitro, and (2) examined CpG methylation and levels
      of methylated histone H3 lysine-27 in the promoter regions of these genes in the
      prefrontal cortex of suicide completers and healthy controls. We identified
      several promoter haplotypes in SMS and SMOX, but found no consistent effects of
      haplotype on expression levels in either the brain or in reporter gene assays
      performed in three different cell lines. We also found no overall effects of
      epigenetic factors in determining expression, with the exception of a
      relationship between CpG methylation at one site in the promoter of SMOX and its
      expression in Brodmann area 8/9. In conclusion, the genetic and epigenetic
      factors examined in this study show little influence on the expression levels of
      SMS and SMOX, and do not appear to be responsible for the dysregulated expression
      of these genes in suicide completers.

PMID- 20059805
TI  - F15599, a highly selective post-synaptic 5-HT(1A) receptor agonist: in-vivo
      profile in behavioural models of antidepressant and serotonergic activity.
AB  - F15599 is a novel agonist with high selectivity and efficacy at serotonin 5
      HT(1A) receptors (5-HT(1A)Rs). In signal transduction, electrophysiological and
      neurochemical tests, F15599 preferentially activates post-synaptic 5-HT(1A)Rs in
      rat frontal cortex. Such a profile may translate to an improved profile of
      therapeutic activity for mood disorders. The in-vivo effects of F15599 were
      therefore compared with those of a related compound, F13714, in rat models of
      antidepressant activity and 5-HT(1A)R activation: forced swimming test (FST),
      conditioned stress-induced ultrasonic vocalization, 5-HT syndrome, plasma
      corticosterone and body temperature. Acute administration of F15599 or F13714
      reduced immobility in the FST at low doses; these effects were long lasting and
      the effects of F15599 were maintained after repeated (5 d, p.o.) administration.
      Both compounds decreased ultrasonic vocalization duration at low doses. In
      contrast, higher doses of F15599 were required to induce lower lip retraction,
      elements of the 5-HT behavioural syndrome, hypothermia and to increase plasma
      corticosterone levels. Notably, there was a greater separation of ED50 between
      FST and other effects for F15599 than for F13714. Thus, the in-vivo potency of
      F15599 in models of antidepressant/anti-stress activity is similar to that of
      F13714, despite the fact that the latter has an in-vitro potency two orders of
      magnitude greater. In contrast F15599 has a lower propensity than F13714 to
      induce other serotonergic signs. The distinctive pharmacological profile of
      F15599 suggests that preferential targeting of post-synaptic 5-HT(1A)Rs
      constitutes a promising strategy for improved antidepressant therapy.

PMID- 20059806
TI  - [Cross-reaction evaluation of PCR-Anaplasma platys positive dogs tested to
      Anaplasma phagocytophilum antibodies by commercial ELISA].
AB  - Anaplasma platys, agent of canine cyclic thrombocytopenia parasites exclusively
      dogs platelets. Its probable vector is the tick Rhipicephalus sanguineus. Among
      the existent diagnostic methods, the most used include: morulae identification in
      blood smears; antibody detection by indirect immunofluorescence; or DNA
      amplification by polymerase chain reaction (PCR). Recently a new commercial ELISA
      (IDEXX(r)), capable of detecting A. phagocytophilum antibodies, has been
      developed. According to the manufacturer it appears to have a serological cross
      reaction with A. platys which may be used to help in the diagnosis of this agent.
      The aim of this study was to test serum samples from 16 PCR-positive dogs to A.
      platys with an ELISA that detects antibodies to A. phagocytophilum, Borrelia
      burgdorferi and Ehrlichia canis, and antigens of Dirofilaria immitis in order to
      verify the occurrence of cross reaction between A. platys and A. phagocytophilum.
      All animals tested negative for A. phagocytophilum, B. burgdorferi, and D.
      immitis. One animal tested positive for E. canis. Although it's known that A.
      phagocytophilum presents serological cross reaction with A. platys, the tested
      animals were negative, once antibodies against A. platys were not detected
      probably because of the acute phase of the disease.

PMID- 20059807
TI  - [Immunization with synthetic peptide anti-tick Rhipicephalus (Boophilus)
      microplus SBm7462 via mucosal routes].
AB  - The mucosal immunization consists on antigen administration in these surfaces it
      is a not invasive method, inductor of local and systemic immune response. This
      work evaluated the immune response of the synthetic vaccine anti-tick
      Rhipicephalus (Boophilus) microplus SBm7462(r), via oral and nasal routes. Were
      used 60 BALB/c mice, divided in three groups of 20 animals each (I: oral
      immunization; II: nasal immunization; III: animals not immunized). Nine and 15
      days after the first and the second immunization was collected, separately for
      each group, T cells from the immunized animals, cultivating them per 10 days.
      After the incubation, were determined the percentage of cellular viability and
      the specific nature of this T cells, which had held as memory T cell. The
      averages of T cell SBm7462-reagents had been submitted to the analysis of
      variance and comparison for Tukey test, 5% of probability. Group II presented
      higher cellular proliferation "in vitro". For ELISA test, were positive only two
      animals in group I and eight in group II. The oral and nasal routs alternatively
      viable for immunization with the synthetic peptide SBm7462(r), however require
      greater number of doses to induce responses with high levels of immunoglobulins.

PMID- 20059808
TI  - Biological parameters of ticks (Amblyomma cajennense Fabricius, 1787) under field
      and laboratory conditions in Pedro Leopoldo, State of Minas Gerais, Brazil.
AB  - This study evaluated the biological parameters of the duration of the pre
      oviposition and egg incubation periods and maximum survival of unfed larvae,
      under field and laboratory conditions, with the aim of providing support for more
      rational measures for controlling Amblyomma cajennense. This study was conducted
      at the Experimental Farm of the Veterinary School of the Federal University of
      Minas Gerais. Every 14 days, from September 1997 to March 1998 and from October
      1998 to April 1999, six netted tubes containing engorged females were kept on
      pasture of Brachiaria decumbens that was up to 60 cm high and another six were
      kept in a BOD glass chamber (27 degrees C, 80% relative humidity). For both
      groups, 84 and 72 females were used during the first and second observation
      periods, respectively. The duration of the pre-oviposition period was similar
      under both conditions (5-7 days). Significant differences were seen between the
      duration of the egg incubation period under field conditions (56 to 60 days) and
      under BOD conditions (34 to 39 days); and between the maximum survival of the
      unfed larvae under field conditions (14 months) and under BOD conditions (9.5
      months). These suggest that behavioral diapause was occurring. The long survival
      of unfed larvae in pasture needs to be considered when implementing Amblyomma
      cajennense control programs.

PMID- 20059809
TI  - [Molecular analysis of the antigenic sequence (SBm7462(r)) from Bm86 of the
      Rhipicephalus (Boophilus) microplus and similarity with Rhipicephalus sanguineus
      and Hyalomma anatolicum anatolicum].
AB  - The vaccination represents optimum method evaluated with effective cost to
      prevent economic losses and to increase the duration and quality of life of the
      production animals. . Diverse vaccines are produced from the intestinal protein
      Bm86 of the Rhipicephalus. (B.) microplus. The knowledge of the conservation of
      the gene bm86 is very important to evaluate the vaccine efficiency and the
      possibility of reaction crossed between different species of ticks. Samples of R.
      (B.) microplus come from different localities had been sequenced. The analyses of
      multiple alignments of the sequences had been made through the BioEdit program
      7.0.5.3 version and the verification of polymorphism for visual inspection. In
      this work the alignment of all was become fulfilled sequences using itself BLAST
      in the search for similarity. Similarity was observed enters the sequenced
      fragments of R. (B.) microplus with the sequence of the protein Rs86 de
      Rhipicephalus sanguineus and with protein HA98 of the tick Hyalomma anatolicum
      anatolicum. The results give molecular support to synthetic the vaccine use based
      in the gene bm86 (SBm7462(r)) to be used in different species of ticks.

PMID- 20059810
TI  - [Ectoparasites of the Nile tilapia (Oreochromis niloticus) bred in net-tanks in
      the Corvo and Guairaca rivers, state of Parana, Brazil].
AB  - Current experiment estimates the prevalence of ectoparasites of the Nile s
      tilapia (Oreochromis niloticus), strain Chitralada, bred in net-tanks during 130
      days, from April to August 2006, and reports on the water's physical and chemical
      parameters. Three hundred and eighty-seven samples of tegumentary scrapes and
      branchia of post-reversed males were analyzed. Experiment was conducted in thirty
      6.8 m-3 net-tanks (2.0m x 2.0m x 1.7m), filled with 6.0 m-3 water, of which 15
      were placed in the Corvo river and 15 in the Guairaca river, with three stocking
      densities (100, 150, 200 fish per m-3) and five repetitions each. At the start of
      experiment, total ectoparasites prevalence in 105 fish, average weight 35.4 +/-
      19.3g and total length 11.7 +/- 2.1cm, was 87.6%. Prevalence was higher for
      Monogenoidea (40.0%), followed by mixed parasitism (33.3%) and Tricodinids
      (14.3%). Whereas in the Corvo river total ectoparasites prevalence in the four
      collections reached 38.2%, with predominance for Monogenoidea (19.4%), in the
      Guairaca river prevalence reached 44.2%, with predominance for Tricodinids
      (17.4%). Water's physical and chemical parameters, with the exception of
      temperature, fitted conditions for Nile s tilapia breeding.

PMID- 20059811
TI  - [Elaboration and evaluation of a candidate to the DNA vaccine using synthetic
      genes derived from the peptideo SBm7462 against the carrapato Rhiphicephalus
      (Boophilus) microplus].
AB  - Rhiphicephalus (Boophilus) microplus is one of the most important arthropods in
      veterinary medicine due economic losses and health problems caused in cattle
      production. The vaccination represents optimum method evaluated with effective
      cost to prevent economic losses and to increase the duration and quality of life
      of the production animals. A synthetic peptide, SBm 7462, derived from Bm86, has
      been shown great results in control of ticks. The construction and synthesis of
      one nucleotide sequence based on this peptide might be useful for design a DNA
      vaccine that has many advances than peptide vaccine. A gene, called seq1, was
      constructed with a three repetition of nucleotide sequence of SBm 7462. It was
      cloned into a pCIneo vector expression in mammals and injected in BALB/c mouse.
      When mice were inoculated with the expression cassette they did not response in
      ELISA. They elevated antibody titles only when vaccinated with the synthetic
      peptide SBm7462(r). And, the best titles of immunoglobulins were seen when the
      SBm7462(r) was administered subcutaneously.

PMID- 20059812
TI  - [Artificial feeding through capillaries tubes of engorged partially females of
      the tick Dermacentor (Anocentor) nitens].
AB  - Artificial feeding is an important toll for studying ticks feeding mechanism and
      transmission of pathogenic agents in the absence of vertebrate host. The
      objective was to feed artificially of engorged partially females of Dermacentor
      (Anocentor) nitens, proceeding of infested naturally equines and evaluate the
      influence of this technique on biological parameters of species. Engorged
      partially females were collected, weighted and separate by weight in two range of
      40 to 60 milligrams and 61 to 100 milligrams. Each range was further sorted in
      four groups with homogeneous weight which were fed for 6, 12, 24 and 36 hours
      through capillaries tubes containing citrated bovine blood. It was observed that
      artificial feeding promoted increase weight of females in both range and
      definitive times. The Ticks fed artificially for periods more drawn out, had
      presented parameters of the non-parasitic phase next to the observed ones in
      conditions to laboratory for this species. Females of D. (A.) nitens partially
      engorged ingested great volume of blood when submitted to artificial feeding
      through capillaries tubes, without any effect in their biological parameters.

PMID- 20059813
TI  - [Performance and parasitologic infestation of male dairy cattle supplemented with
      proteic salt containing or not homeopathic medicines].
AB  - The objective of this study was to evaluate the performance and parasitologic
      infection of male dairy cattle submitted to supplemental proteic salt with and
      without the use of homeopathic medicines. Were used crossbred Gir x Holstein
      castrated males calves, with 10 months of age and live weight of 150.75 kg,
      distributed in a completely randomized design with eight replicates per
      treatment, totaling 16 animals. The calves of each treatment remained in a
      pasture of Brachiaria brizantha cv. Marandu, managed in continuous grazing system
      for 8 months. The treatments employed were: supplementation with 300 g/animal/day
      of protein (40% of crude protein (CP) and 25% CP in the dry and rainy season,
      respectively) added or not with 5 g/animal/day of the homeopathic medicines FATOR
      PRO(r) and C & MC(r). The addition of homeopathic medicines in the protein
      supplement did not affect (P > 0.05) the development of body male crossbred to
      pasture. The counting of the larvae and adults of ticks in scrapings were lower
      (P < 0.05) in animals that did not receive homeopathic medicines in the protein
      supplement. The females tick in the body anterior third (simplifying counting),
      nymphs in scrapings and the number of eggs per gram of helminths were not
      affected (P > 0.05) by the treatments. It was concluded that the use of
      homeopathic medicines did not affect the development of male crossbred Gir x
      Holstein dairy cattle neither their parasitic infection.

PMID- 20059814
TI  - [Biological aspects of Argas (Persicargas) miniatus Kock, 1844, (Ixodoidea;
      Argasidae) larvae in Gallus gallus].
AB  - The aim of the present study was to describe the biological aspects of larvae of
      Argas miniatus at 27+/-1 masculineC and 80+/-5% and in environmental condition.
      Domestic fowls with age lower than one week were infested with approximately 700
      larvae of A. miniatus 15 days posthatching. The period of larval fixation varied
      from 3 to 7 days in four repetitions. Approximately 90% of larvae were recovered
      in the 4th and 5th day after attachment. The mean weight increased approximately
      81.37 times the initial weight of the unfed larvae. The mean larval mortality in
      controlled conditions and laboratory environment were 6.35% and 13.97%,
      respectively. Molting period varied from 4 to 9 days in controlled condition,
      while in the environment conditions the interval varied from 5 to 15 days. The
      larval longevity was 120 days, in both conditions. Unfed larvae maintained at
      27+/-1 masculineC and 80+/-5% and environment condition were capable to attach
      from 6 to 60 days and 8 to 45 days, respectively.

PMID- 20059815
TI  - [Seasonal dynamics of Amblyomma ticks (Acari:Ixodidae) in an urban Park of
      Londrina City, Parana, Brazil].
AB  - Ticks are important to public health due to diseases they transmit to animals and
      humans and, economic losses they cause to livestock production. Among other
      agents, such as Babesia, Ehrlichia, Anaplasma, the Rickettsia are the most
      important pathogens transmitted by ticks in Brazil. Worldwide there are about 870
      tick species described and, of these, 55 species were already reported in Brazil,
      being the genus Amblyomma the most numerous with 33 species. The A. cajennense is
      the principal tick involved in the transmission of the Brazilian Spotted Fever.
      New cases of the disease, in some regions of Brazil, have been associated with
      the increment of the capybara population, wild animal considered primary host for
      A. cajennense and A. dubitatum. The objectives of this work were to identify and
      study the population dynamic of free-living ticks species presents in the Arthur
      Thomas Municipal Park, where lives a group of capybaras, among other wild animals
      and birds. From August 2006 to July 2007, free-living nymph and adult tick stages
      were collected using carbon dioxide traps, and for larvae capture was used the
      technique of the dragging with white flannel. All the ticks captured were
      transported to the laboratory, fixed in ethanol, counted and identified by
      morphological criteria. The three stages of the genus Amblyomma spp were present
      all over the 12 months of the studied period. Larvae and nymphs were present in
      the park all over the year with population peaks in both semesters of the studied
      period. Adult of A. cajennense were more abundant on the ground of the park
      during the spring-summer months and, A. dubitatum presented populational peaks in
      September/ October, 2006 and July, 2007. Considering these data it can be
      concluded that visitors and people that work in the park are exposed to the ticks
      all over the year, with larger risk of attacks in the hottest months.

PMID- 20059816
TI  - [Efficacy of the pyrethroid permethrin on the control of Psoroptes ovis (Hering,
      1838) (Acari:Psoroptidae) in naturally infested rabbits (Oryctolagus cuniculus)].
AB  - The goal of the present study was to evaluate the efficacy of a spray formulation
      containing 2% of the pyrethroid permethrin on the control of Psoroptes ovis in
      naturally infested rabbits. Ten rabbits, presenting clinical signs of psoroptic
      mange in both ear canals. The animals were divided into two groups of five:
      control, without treatment (GI) and a second group (GII) treated with a single
      application of 2% permethrin. The diagnosis was realized by collecting fragments
      of crusts from both ear canals and submitting to stereomicroscopy for the
      presence and evaluation of mites' motility. On day 0 the animals from GII were
      treated topically with 2mg of 2% permethrin in each ear canal. No other treatment
      or environmental decontamination was performed during the trial. The rabbits were
      evaluated daily for observation of possible side effects. To evaluate the
      efficacy, collections of material were undertaken on days: +7, +14, +21. The
      formulation containing 2% permethrin was 100% effective in the control of P. ovis
      in naturally infested rabbits, along all days of observation. No adverse
      reactions were observed in the treated animals.

PMID- 20059817
TI  - [Control of Anocentor nitens (Neumann, 1897) (Acari: Ixodidae) on equines].
AB  - This trial evaluated control practices of Anocentor nitens on equines, using
      spraying devices and application of acaricide paste formulation in the auricular
      pavilion and nasal diverticulum. The study was carried out from October 2003 to
      March of 2008 and the evaluations had been divided in the following stages: Phase
      1--out/03 mar/04 and Phases 2, 3, 4 and 5, respectively, correspondents to the
      month's periods until marco/08. It was used score of 0 to 3 to classify
      infestation levels. From abr/04 to mar/06 was implanted a schedule of acaricide
      sprayings every seven days and divided in two series. The first one beginning in
      April 2004 and the second beginning in July, both using six sprayings treatments
      with pyrethroid chemical base--cypermethrin 0,015%, plus topical treatments
      applied monthly in the auricular pavilions (powder acaricide). From abril/06 to
      marco/08 was carried out similar schedule treatments, each two months, using an
      experimental acaricide paste in the auricular pavilion and nasal diverticulum.
      Phases 2 and 3 did not showed reduction of the parasitic loads of A. nitens
      compared to the control period. Whereas in Phases 4 and 5 registered significant
      reduction compared control period and also with the results of Phases 2 and 3,
      characterizing the effectiveness of the treatment with the acaricide paste
      formulation. Results demonstrated of A. nitens populations present in the nasal
      diverticulum are important in the maintenance of the infestations on equines, and
      necessary attention to this anatomical structure when controlling ticks.

PMID- 20059818
TI  - [Effect of the urea fertilization in pasture on Rhipicephalus (Boophilus)
      microplus (Acari: Ixodidae)].
AB  - The objective of this study was to verify the effect of the urea fertilization in
      pasture on Rhipicephalus (Boophilus) microplus population in free living stage.
      Two groups had been made, a control group and a urea treatment group, each group
      with 10 lots of Mombaca grass (Panicum maximum cv. Mombaca). In day zero had been
      placed 12 engorged tick females in each lot and made fertilization with urea in
      the dosage of 60 g in the lots of the treat group. In 27th day the grass was
      cutted out in 1 to 5 lots of both groups and fertilized with urea in the lots of
      1 to 5 in the treat group. In 40th day was released a white flannel 1.60 x 1.00 m
      length on each lot to verify the presence of larvae. The results presented a
      difference of 85.97% (P < 0.0001) between the treat group and the control group.

PMID- 20059819
TI  - [Ectoparasites of small wild mammals from the adjacent areas of Itapecuru River
      and Environmental Preservation Area of Inhamum, state of Maranhao, Brazil].
AB  - During fauna studies, thirty-six wild mammals were collected in adjacent areas of
      Itapecuru River and Environmental Preservation area of Inhamum, state of
      Maranhao, Brazil. They were sampled for ectoparasites. The following specimens of
      the order Rodentia and its respective ectoparasites were identified: Akodon sp.
      (Androlaelaps sp. and Laelaps sp.), Oecomys sp. (Androlaelaps sp. and Amblyomma
      cajennense), Oligoryzomys sp. (Androlaelaps sp. Laelaps sp. and Amblyomma sp.) e
      Oryzomys megacephalus (A. cajennense). In Calomys callosus no ectoparasite was
      found. It was observed infestation in the order Didelphimorphia as follows:
      Didelphis marsupialis (Androlaelaps sp., Laelaps sp. and larvae of Diptera
      Cyclorrhapha); Gracilinanus sp. (Laelaps sp. and larvae of Diptera Cyclorrhapha),
      Monodelphis domestica (Poplygenis (Polygenis)), Cummingsia sp., Amblyomma sp. and
      Androlaelaps sp.). Marmosa sp. e Thylamis sp. had no ectoparasites. From the
      captured hosts 56% were infested, 82% and 44% rodents and marsupials,
      respectively. Mites from the family Laelapidae presented the great diversity of
      hosts and genus.

PMID- 20059820
TI  - [Efficacy of eprinomectin in the control of Haematobia irritans in cattle].
AB  - To evaluate the efficacy of a formulation with 0,5% of eprinomectin in cattle to
      control H. irritans, two trials were conducted for the control of H. irritans in
      the field in the state of Rio de Janeiro, using 0,5% of eprinomectin, at a dose
      rate of 500 mc g/kg body weight, corresponding to 10 mL/100 kg. The efficacies
      for days +7, +14, +21 e +28 after treatment were respectively 100%; 94,3%; 86,2%
      and 24,5% for the first study and 100%, 100%, 100%, and 0% for the second one.

PMID- 20059821
TI  - [Seasonal dynamics of the free-living stages of Amblyomma cajennense and
      Amblyomma dubitatum (Acari: Ixodidae) in an endemic area for spotted fever in
      Coronel Pacheco region, Minas Gerais State].
AB  - A study on the population behavior of Amblyomma cajennense and Amblyomma
      dubitatum larvae, nymphs and adult free-living stages was carried out in Coronel
      Pacheco County, Minas Gerais State, Brazil, a spotted feverendemic area from May
      2006 to April 2008. Larvae of Amblyomma sp. were collected from pasture using the
      technique of drag sampling with flannelette during May to October 2006, starting
      from February 2007 to November 2007 and starting from March 2008. Well-defined
      peaks of populations occurred in May 2006, April-May 2007, April 2008 and October
      November 2007. Nymphs were captured throughout the year by the use of traps with
      carbon dioxide and peaks populations were observed between June and November.
      Adults occurred throughout the year with an increase in population density from
      October to March and from August to April for A. cajennense and A. dubitatum,
      respectively, during the two years of experiment. Were identified peaks
      populations in October- November 2006 and 2007, January-February 2007 and 2008
      for A. cajennense and October-November 2006 and 2007, February-April 2007 and
      2008 for A. dubitatum. These results show that a different seasonal pattern for
      freeliving stages of A. dubitatum regarding the population of A. cajennense in
      the study area.

PMID- 20059822
TI  - [Efficacy of extracts of plants in engorged females of Boophilus microplus from
      the mesoregion West of Maranhao, Brazil.].
AB  - The objective was to evaluate the efficacy of hydro-alcoholic extracts of nim and
      citronela at 20% and eucalipto at 10% in Boophilus microplus engorged females
      collected in cattle naturally infected from the mesoregion West of Maranhao. At
      the laboratory the females were separated, weighted and distributed in six groups
      of 10, in duplicate. Each group was immersed in 10mL of the solution of the
      extracts, for two minutes. In the nim and citronela extracts there was 32% e 17%,
      respectively, while larval emergence the eucalipto extracts demonstrated 96% of
      efficacy. In the groups treated by Cipermetrina + Clorpirifos + Citronetal and
      Deltametrina (positive controls) the mortality occurred after 48h of treatment,
      while the groups immersed in distilled water (negative control) showed 100% of
      eggs mass and larval emergence. According to the results, it can be concluded
      that the extract of eucalipto could be used as acaricide in the control of B.
      microplus females since it was efficient in vitro, however to nim and citronela
      showed not efficacy. B. microplus females were not resistant to the chemical
      compounds used in this experiment.

PMID- 20059823
TI  - [Activity of neem extract on the embryonary development of Ctenocephalides felis
      felis (Bouche, 1835) (Siphonaptera: Pulicidae)].
AB  - The present study had as objective to evaluate the activity of limonoid
      azadiractin, extracted of the seeds of the plant Azadirachta indica, neem, on the
      embryonary development of Ctenocephalides felis felis. A dog was sprayed with the
      formulation 10%, another dog was kept as control, without treatment. Both had
      been infested weekly with 600 fleas, in the ratio of 1:1 between males and
      females. The deriving positions of the infestations had been incubate per seven
      days in assay pipes, and evaluated it percentage of emerging of flea eggs,
      comparing themselves the averages of the groups treat and have controlled. The
      extract of nim presented activity on the embryonary development of C. f. felis,
      keeping superior levels of effectiveness 80% until day +14, beyond diminishing
      the position and inhibiting the development between urging larval of the
      percentage of larvae that had come out.

PMID- 20059824
TI  - [Effects of the oxitetracycline in the increase of the packed cell volume of cows
      milk jugs during outbreak of bovine anaplasmosis].
AB  - This research was performed to study the effects of oxytetracicline L.A., in
      unique dose, in the reconstitution of the packed cell volume (PCV) from animals
      clinically affected by anaplasmosis. Were utilized 152 Holstein Frisian Cows, of
      first lactation with age group varying between three and four years old. The
      animals were classified according to the presence of Anaplasma marginale in the
      circulation and percentage of PCV as: chronic infection (PCVe24%) and clinical
      (PCV<23%) constituting groups of 117 and 35, respectively. The animals with
      clinical infection were treated when detected the parasite by microscopy
      examination in stained thin blood smears and when the PCV were less than 24%; the
      animals with chronic infection were not treated and maintained like group control
      of the infection. All treated animals with 20mg.Kg-1 of oxitetracycline showed
      recuperation increasing for levels close to the physiological parameters. The
      animals considered with PCV normal for the category, in the day 0, were not
      treated and had tendency to the fall. The results reveal the activity of the
      oxytetraciclyne in the recuperation of clinical cases with anemia by bovine
      anaplasmosis.

PMID- 20059825
TI  - [Accidental myiasis by Ornidia obesa in humans].
AB  - Dipterous of the genus Ornidia are pollinator bugs, but immature stages can be
      found in organic matter in decomposition. This article refers to a found of
      larvae of Ornidia obesa in humans feces. An eight years old child was treated in
      a medical clinic due to the presence of two larvae and one pupae in the feces,
      hyperthermia, intestinal obstruction and strong abdominal pain. Medical therapy
      consisted of Mebendazol and Ivermectin in the indicated doses. 24 hours after the
      administration of the drugs, several larvae were expelled with diarrheic feces.
      The material was taken to the Parasitological Veterinary Lab, and the larvae were
      classified belonging to the genus Ornidia. According to the literature, this
      specie of Diptera is not incriminated to cause myiasis in vertebrates. We think
      that this study reports a case of accidental myiasis in humans, were the patient
      may have ingested food with immature stages of the fly (eggs or larvae).

PMID- 20059826
TI  - [Infestation by Ornithocoris sp. at dwellings in the Municipality of Santa Maria,
      Rio Grande do Sul State, Brazil].
AB  - Ornithocoris is a Hemiptera of the family Cimicidae that parasitizes wild and
      domestic birds. We considered opportune to report two isolate cases of parasitism
      by Ornithocoris sp. at dwellings in the municipality of Santa Maria, RS. In both
      cases, the residents reported the presence of insects at the night, besides
      intense prurid and red spots, typical of insect bites. All residents were
      affected, besides a dog. A great quantity of Ornithocors sp. specimens was seen
      on the walls, bed and leg of a child, while sleeping. Both cases occurred in the
      spring season when bird nests were seen near houses. It suggests that this blood
      sucking insect fed on humans in the absence of birds, their natural hosts.

PMID- 20059827
TI  - Chemical and biological stability of artemisinin in bovine rumen fluid and its
      kinetics in goats (Capra hircus).
AB  - There is a pressing need to develop alternative, natural anthelmintics to control
      widespread drug-resistant gastrointestinal nematodes in ruminants, such as
      Haemonchus contortus. Artemisinin and its semi-synthetic derivatives are widely
      used against drug-resistant Plasmodium falciparum, but their role in veterinary
      medicine is only emerging. Artemisinin may be useful in controlling
      gastrointestinal parasites including Haemonchus. However, no ruminant studies
      involving artemisinin have been reported. The stability of artemisinin in
      capsules, crystals, or stock solutions in ethanol and dimethyl sulfoxide was
      evaluated in bovine rumen culture medium incubated for 24 hours at 39 degrees C.
      A second study established artemisinin kinetics in goats after oral
      administration of artemisinin capsules at 23 mg/kg of body weight. Artemisinin
      recovered from rumen culture ranged from 67 to 92% at pH 6.8 and was 95% at pH
      3.0. The kinetics data showed that artemisinin was metabolized to
      dihydroartemisinin by goats, while unabsorbed artemisinin was eliminated in
      feces. Dihydroartemisinin peaked in the blood (0.7 mug/mL) at 12 hours, and
      decreased to 0.18 mug/mL at 24 hours. At 24 hours, artemisinin concentration in
      feces was 2.4 mug/g, indicating its poor bioavailability in goats when provided
      orally and as capsules. These results suggest that the bioavailability of
      artemisinin to goats can improve by dissolving capsules in ethanol or dimethyl
      sulfoxide, by using more stable and bioavailable artemisinin-derived drugs, and
      by using routes of delivery other than oral.

PMID- 20059828
TI  - [Sensibility and reproducibility of a sedimental technique (Foreyt, 2005) for
      Fasciola hepatica diagnosis].
AB  - The purposes of this study were to evaluate the sensibility and reproducibility
      of Foreyt (2005) technique in the diagnosis of Fasciola hepatica. A total of 686
      bovines were examined at a slaughtered house and 97 were positive for Fasciola
      hepatica. Feces samples were collected and 58 were positive for the Foreyt
      technique. The validity was tested by the sensibility (59.8%) and specificity
      (100%). The reproductability, calculated by the Kappa agreement was 0.70 and the
      Chi-square showed differences between the tests (p < 0.001).

PMID- 20059829
TI  - [The endoparasitic helminths of Pimelodus maculatus Lacepede, 1803 Siluriformes,
      Pimelodidae) from the two localities (Lagoon and gutter of the River) of the
      Guandu River, State of Rio de Janeiro, Brazil].
AB  - Between November 2003 and March 2004, fourty specimens of Pimelodus maculatus
      Lacepede, 1803 from Guandu River and thirty-nine from Guandu Lagoon (Nova Iguacu,
      RJ) were collected, for the analysis of endoparasitic fauna. A total of 236
      specimens of Cucullanus pinnai Travassos, Artigas & Pereira, 1928 (Nematoda,
      Cucullanidae) were collected, being 163 adult specimens in the gut, three in the
      stomach and 70 larvae in the celomatic cavity and seven specimens of adults
      Nomimoscolex sp. (Eucestoda, Proteocephalidea) in the gut were found. Cucullanus
      pinnai presented prevalence (P) 77.50%, mean intensity (MI) 3.40 and mean
      abundance (MA) 2.60 on River and P: 66.67%, MI: 5.04, MA: 3.36 on Lagoon.
      Nomimoscolex sp. presented on River P: 2.50%, MI: 2.00, MA: 0.05, and P: 10.26%,
      MI: 1.25, MA: 0.13 on Lagoon. There was not significant positive interspecific
      association on the lagoon. In this research, the endoparasitic richness of P.
      maculatus was scarcest than similar studies in Guandu River and others rivers of
      different basins. The results about C. pinnai could be suggesting that the cycle
      of C. pinnai evolve only a host, occurring a histotrophic fase, in this case, in
      P. maculatus. Periodic analysis of the endoparasites indices in P. maculatus
      through the years may be used to describe the hydric quality of the Guandu River.

PMID- 20059830
TI  - [Evaluation of the efficacy of antihelmintics compounds on parasitics
      gastrointestinal nematodes (Strongyloidea) of goats].
AB  - The present study was performed in order to evaluate the action of anthelmintics
      compounds on gastrointestinal parasite nematodes of 27 Alpine and Saanen adult
      goats. The animals were divided into three groups. The animals of groups 1 and 2
      had been dealt with two different associations of antihelminthics in day zero.
      The goats in group 1 were treated with closantel (75 mg/mL), albendazol (38
      mg/mL) and ivermectin B1a (2 mg/mL) orally (1 ml/ 10 Kg body weight); animals in
      group 2 were treated with closantel (100 mg/mL), albendazol (50 mg/mL), levamisol
      (64 mg/mL), ivermectin B1a (2 mg/mL), selenium (1 mg/mL) and cobalt (4.4 mg/mL)
      orally (1 ml/10 Kg of body weight) and the animals in the group 3 (control)
      received distilled water. Eggs per gram counts on faeces (EPG) and coprocultures
      of all animals were made at intervals of days 0, 3, 5, 7, 14, 21 and 28. The
      haematocrit, global counting and differential white blood cells, total protein
      and the Famacha test were determined at intervals of days 0, 14 and 28. Six
      animals of each group had suffered euthanasia and slaughters on the 28th day. The
      results showed that only the combination used in the animals of group 2 was
      effective.

PMID- 20059831
TI  - [Gastrointestinal nematode parasitism in ewes and lambs raised in Sao Carlos, Sao
      Paulo].
AB  - Gastrointestinal nematode infections were evaluated in Santa Ines crossbreed
      sheep (Santa Ines predominance) in a rotational grazing system and in lambs kept
      indoors, born from the breeding of these females with purebred Santa Ines, Dorper
      and Suffolk males. Fecal egg counts (FEC), fecal cultures, packed cell volume
      (PCV) and weights were evaluated during two years. Climate data were registered.
      Only animals that presented FEC higher than 4,000 and/or PCV lower than 21% were
      drenched with anthelmintic treatment and this rational use controlled the
      infection in the flock satisfactorily. An adequate diet during the rainy season
      and supplementation in dry period were important to increase relative resistance
      and resilience to parasites, since Haemonchus contortus was detected year-round
      in this region. The peripartum physiological condition influenced
      gastrointestinal nematode infections significantly. Crossbred (1/2) Santa Ines +
      (1/2) Dorper lambs did not show a significant difference in FEC when compared
      with other breeds, but they had greater live weight and reached slaughter weight
      earlier.

PMID- 20059832
TI  - [Comparison of the efficacy of different isolates of the nematode-trapping fungi
      Arthrobotrys spp. and Duddingtonia flagrans in reducing infective larvae of
      nematodes after passage through the digestive tract of sheep].
AB  - For oral application in ruminants, nematophagous fungi must has the capacity to
      survive the passage through the digestive tract and be efficient in reducing
      infective larvae of nematodes in the faeces. In this work, these capacities were
      evaluated and compared in Brazilians and Canadians isolates of Duddingtonia
      flagrans, Arthrobotrys musiformis and A. oligospora. Fungi were cultured in Rouxs
      Bottles with corn grain as a growth media, and a suspension of 700,000
      chlamydospores (D. flagrans) or conidia (A. oligospora and A. musiformis) per Kg
      of body weight was administered orally for three consecutive days to a group of
      sheep naturally infected with gastrointestinal nematodes. The control group did
      not receive fungi. The faeces of these animals were colleted for 3 days pre and 3
      days postadministration of the suspension and the number of eggs per gram of
      faeces (EPG) and fecal cultivations carried out. Infective larvae (L3) were
      recovered through baermanization, quantified and compared together with the EPG
      values. Only administration of D. flagrans significantly reduced the percentage
      of L3 in the fecal cultivations by more than 95%. These results indicate the
      potential of D. flagrans as a biological control agent for sheep nematodes.

PMID- 20059833
TI  - [The relationship between the peri-parturient period and output of nematodes eggs
      in naturally infected Anglo Nubiana goats in a semi-extensive system of
      production].
AB  - The purpose of this study was to identify the relationship between the excretion
      of nematodes eggs in naturally infected Anglo-Nubians breed goats under
      conditions of semi-extensive production system and the peri-parturient period.
      Were used 63 goats, with weight average 35, 05 +/- 6, 54 kg and reproductive
      cycle from goats. Animals were separated and two groups homogeneous as to the age
      and nutritional status and two groups (pregnants and nonpregnants). Faecal
      samples were collected weekly during the periparturient period (ended four weeks
      of pregnancy and the four first weeks of post-parturition) and equal dates in non
      pregnants group. The group of pregnant animals showed increasing EPG (eggs per
      gram of faeces) in the 5th and 8th week of collection and animals not pregnant
      and in the 5th and 6th week. The highest counts of EPG were coincident with the
      highest concentration of births; there is a direct relationship between to
      release eggs from gastrointestinal nematodes in the female goats, near to birth.

PMID- 20059834
TI  - In vitro effect of condensed tannin extract from acacia (Acacia mearnsii) on
      gastrointestinal nematodes of sheep.
AB  - The aim of this study was to determine the inhibitory effects of condensed tannin
      extract from acacia on the feeding of first-stage larvae (L1) of Haemonchus
      contortus, Trichostrongylus vitrinus and Teladorsagia circumcincta. The
      experiment was developed such that the inhibition of feeding for each of the
      nematode species could be evaluated. L1 recovered from fecal samples from a donor
      with monospecific infection was incubated in several dilutions of acacia extract
      (AE). The LD50 was determined for the three species of nematodes. Polyethylene
      glycol (PEG) was added to all dilutions of AE to inactivate the condensed tannins
      (CT) from acacia and to confirm their effects on L1. The impact of CT on larval
      feeding inhibition was detected for all the species of nematodes (H. contortus,
      T. colubriformis and T. circumcincta). There were differences between the
      aqueouswater control and CT treated groups (P < 0.01). The LD50 values were
      0.043, 0.038 and 0.050 (SE = 0.0024), for H. contortus, T. vitrinus and T.
      circumcincta, respectively. A difference was detected between the AE and AE + PEG
      treatments (P < 0.01). Analysis of these results suggested that the direct effect
      of CT on L1 of the nematodes studied could be used as an alternative means for
      controlling nematodes in sheep.

PMID- 20059835
TI  - Triclabendazole resistance involving Fasciola hepatica in sheep and goats during
      an outbreak in Almirante Tamandare, Parana, Brazil.
AB  - Fasciolosis is a disease of extreme importance, occurring throughout Brazil, with
      great economic losses to the animal industry. This study aims to determine the
      effectiveness of treatment against Fasciola hepatica on a sheep and goat farm
      during an outbreak of fasciolosis, in which a high proportion of deaths occurred.
      The farm harbored 33 sheep and 60 goats of mixed breeds with varying weights and
      ages. Parasite control was based on suppressive, monthly treatments with
      moxidectin. Over the course of the study, assessments with Famacha method, body
      condition score, faecal exam (EPG), coproculture and the egg sedimentation
      technique were made on seven occasions. At the time of the first visit 81% of the
      goats and 100% of the sheep were positive for F. hepatica. Salvage treatment with
      triclabendazole failed to relieve the heavy infection due to resistance, with an
      efficacy of only 66.3% being obtained against the F. hepatica population
      consensual in sheep and 57.3% in goats. There was no record of triclabendazole
      having been administered previously on the farm. A low level of correlation was
      found between the Famacha values and the incidence of anemia due to clinical
      fasciolosis (C<0.5). There is an urgent need to investigate the correct use of
      available drugs against F. hepatica and the implementation of alternative control
      strategies in endemic areas in order to ensure optimum sustainability of the
      efficacy of available fasciolicides.

PMID- 20059836
TI  - [Preliminary essays to the validation of FAMACHA(c) method in conditions of semi
      arid Paraibano].
AB  - The gastrintestinal helmintiases occupy prominence place among factors that limit
      the farming goat in entire world, especially on tropical regions, where
      economical losses are more accentuated. The objective of this work was to
      evaluate FAMACHA(c) method utilization as an auxiliary strategy on the control of
      parasites of goats in semiarid paraibano. Moreover the clinical assistance,
      values of hematocrit and OPG were determinate to evaluate the relation between
      the exams. They were used 30 moxoto female goats, monthly evaluated for 90 days.
      The female goats that presented degree three of mucose in accordance to the
      FAMACHA(c) method do not need to be vermifuged in accordance with hematocrit and
      OPG values. The FAMACHA(c) method, although too indicated for use in goats, needs
      little adaptation to be best administered.

PMID- 20059837
TI  - [Quantitative prevalence of Anoplocephala sp. and egg shedding consistency in
      horses].
AB  - The objective of this work was to determine the quantitative prevalence of
      Anoplocephala sp. in thoroughbred horses raised in Sao Jose dos Pinhais, PR using
      the modified centrifugal-flotation technique. Repeatability values for the eggs
      per gram (EPG) were evaluated at 28-day intervals. The coproparasitological tests
      were made in 28 one-year old animals, 25 two-year old animals and 28 mares during
      the 2007 period of January 31st and June 15th. In the comparison of EPG, all
      mares presented low values than the foals (P = 0.04). The prevalence results
      indicated 50, 18 and 40% Anoplocephala sp. in mares, one-year old and two-year
      old foals, respectively. The EPG repeatability data indicated that both foal
      generations (2005 and 2006) showed values above 70% and that the mares showed
      values higher than 40%, revealing an optimal condition which could be
      incorporated for breeding program purposes.

PMID- 20059838
TI  - [Coenurosis in a sheep in Santa Catarina State, Brazil].
AB  - Coenurus cerebralis infection is commonly occurring parasite in small ruminants
      worldwide. A ewe showed head inclination to the left, equilibrium loss, impetuous
      movement to the high, falling in left lateral recumbency and recovering movement
      later. Seven days later, the animal remained in permanent lateral recumbency and
      nystagmus. Euthanasia was carried out and a routine necropsy examination was
      performed. A large volume was found on the right side of the cerebellum due to a
      cystic cavity, with approximately 1.5 cm of diameter and it was identified as
      Coenurus cerebralis.

PMID- 20059839
TI  - [Ecological studies on helminthic taxocenosis of sympatric Chaunus ictericus
      (Spix, 1824) and Chaunus schneideri (Werner, 1894) (Anura: Bufonidae) captured on
      Sao Cristovao district, Tres Barras county, Santa Catarina State, Brazil].
AB  - Fifty eight Chaunus ictericus and 42 C. schneideri specimens were collected on
      Sao Cristovao district, Tres Barras, SC for helminthological studies. Fourteen
      helminth species were diagnosed, from which only five species were found on both
      hosts. Chaunus ictericus showed higher values of species richness (2,8448+/
      1,1516) and diversity (H = 1,374), with mild dominance (1-D = 0,642, J = 0,5528),
      in comparison with C. schneideri (0,6428+/-1,007; H = 1,165; 1-D = 0,5822 e J =
      0,5985). Also, descriptors of helminthic infection were superior in the former
      host. Little number of shared species between the analyzed toad species suggests
      parasitic host-specificity.

PMID- 20059840
TI  - [Cysticercus bovis in bovines under federal inspection (SIF) at slaughterhouse in
      mountain region of the State of Rio de Janeiro from 2003 and 2004].
AB  - The purpose of this work was to determine the importance of bovine cysticercosis
      in mountain region of the State of Rio de Janeiro, Brazil, with data from SIF
      193, located at Itaperuna. In this study, data from 23,501 animals were used,
      while 15,078 were analyzed in the first year and 8,423 in the second year, with
      304 (2.02%) animals parasited in 2003 and 225 (2.67%) in 2004. This work studied
      the occurrence of bovine cysticercosis in the region, and tried to show the
      importance of sanitary inspection as a means of preventing human taeniasis.

PMID- 20059841
TI  - [Clinical features and diagnosis of Stephanofilariasis in dairy cows].
AB  - Clinical aspects related to natural stephanofilariasis were investigated in 55
      dairy cows of seven herds, located in Santana do Itarare, PR and Itabera, SP,
      Brazil, from January 2006 to February 2008. Two diagnosis methods using biopsed
      tissue fragments from the border of the skin lesions were compared to confirm the
      presence of the nematode: histopathology (n = 24) and direct sediment examination
      of isotonic saline solution (n = 20). The highest prevalence was observed on
      December to March (60%) and on lactating cows (90,9%). The parasite was not
      detected in any histological examination of the fragments. The direct examination
      enabled the demonstration of the agent in 100% of the samples. The
      stephanofilariasis is a disease prevalent in summer, and is characterized by skin
      lesions located in the fore quarters of the udder of lactating dairy cows. The
      lesion has circular format, is ulcerated with crusts and displays serous and
      blood exudate. The direct sediment examination proved to be efficient for the
      diagnosis confirmation.

PMID- 20059842
TI  - [Parasitological prevalence of cart-horses in Curitiba, Parana].
AB  - The carthorses are used as an alternative for people of low income for collecting
      recyclable material. However, these horses are managed without proper assistance,
      suffering several problems, among them the parasites. In this study we used 41
      animals, their body condition score and other parameters were analyzed and
      parasite egg count was performed from fecal samples. It was determined the
      absence of eggs on 12% and parasite infection in 88%. Strongylids were found in
      all contaminated animals, often associated with oocysts or Parascaris equorum.
      This condition may be due to poor nutritional management and unreasonable work
      load that these animals are submitted. There is an urgent need for improvements
      in the management of health and parasites control programs to these animals.

PMID- 20059843
TI  - [Occurrence of nematodes in horses from the Northern region, State of Tocantins,
      Brazil].
AB  - The occurrence of nematodes in horses of Northern Region, State of Tocantins was
      studied. Fecal samples were collected from 70 horses and 31 donkeys, in a total
      of 101 animals of different ages, in the municipalities of Nova Olinda, Araguana,
      Babaculandia and Santa Tereza. Fecal examination was carried out for counting of
      eggs per gram of faeces, identification and quantification of larvae, diagnosis
      of habronemosis and lungworms. Significant occurrence of large and small
      strongyles and Dictyocaulus sp. was observed but no Habronema spp. larvae was
      detected.

PMID- 20059844
TI  - [Occurrence of gastrointestinal parasites in dogs and cats in the laboratory of
      routine of parasitic diseases FMVZ/Unesp-Botucatu, SP].
AB  - With the object of determining the occurrence and prevalence of parasites in dogs
      and cats in the region of Botucatu, a survey was conducted from the results of
      fecal parasitologic exams feces, processed by the laboratory of parasitic
      diseases of FMVZ-UNESP/Botucatu from January 2002 to December 2006. 1,012 fecal
      samples of dogs and cats were evaluated by the technique of Willis Mollay and
      Faust. In dogs the higher incidence was found for Ancylostoma caninum eggs (38%).
      In cats, the oocysts of Isospora spp were present in 48.38% of positive samples.

PMID- 20059845
TI  - Feline cholangitis/ chonlangiohepatitis complex secondary to Platynosomum
      fastosum infection in a cat.
AB  - Platynosomiasis has been associated with cholangitis/cholangiohepatitis complex
      in domestic cats. Despite being typically asymptomatic, some individuals may
      develop severe disease resulting in hepatic cirrhosis. Definitive diagnosis by
      means of parasite eggs direct visualization is not always possible and
      complementary tests should be associated. This paper reports a case of a three
      year-old female cat with anorexia and jaundice. Ultrasound and biochemistry
      laboratory findings as well as liver biopsy were not conclusive. Definitive
      diagnosis of intense Platynosomum fastosum infestation was only possible through
      direct examination of biliary fluid at necropsy, stressing the importance of
      including platynosomiasis, commonly an underdiagnosed disease, among differential
      diagnoses of feline liver diseases.

PMID- 20059846
TI  - [Anoplocephala sp. prevalence in equines at the Sociedade Hipica Paranaense,
      Curitiba, PR].
AB  - Anoplocephala sp. parasites are among the most frequent tapeworms in equines and
      are associated with intestinal infections. This survey had the objective to
      verify Anoplocephala sp. prevalence at Sociedade Hipica Paranaense (SHPr). The
      animals were treated with ivermectin, which does not have efficacy against
      Anoplocephala sp.. To determine whether eggs of Anoplocephala sp. were present, a
      modified centrifugal flotation technique was used and also eggs per gram of
      faeces (EPG). None of the samples showed Anoplocephala sp. eggs and only 11% of
      the animals had positive values for EPG. The results are explained by the good
      health conditions of the animals and by the constant cleaning of the environment
      at the SHPr.

PMID- 20059847
TI  - [Determination and correlation of anti-Neospora caninum antibodies in cattle and
      dogs from Parana, Brazil].
AB  - The protozoan parasite Neospora caninum is a major cause of abortion in cattle
      worldwide. The aim of the present study was to determine and to compare the
      presence of anti-Neospora caninum antibodies in cattle, as well as in farm dogs,
      and the relationship among them. The research was conducted in different
      mesoregions of Parana state, Southern Brazil. Sera from 1.263 cattle, from 77
      farms were tested for antibodies to N. caninum by ELISA. Sera from 129 dogs, from
      35 farms were tested for antibodies to N. caninum by indirect fluorescent
      antibody test (IFAT). Antibodies to N. caninum were found in 423 of 1.263 bovines
      (33%), and in 32 of 129 dogs (25%). The seroprevalence of antibodies for
      N.caninum in cattle was not significantly higher in farms with seropositive dogs
      when compared to farms with no seropositive dogs. Thus, these results suggest
      that seropositive dogs to N. caninum did not contribute for the seroprevalence in
      cattle. Neospora caninum is widespread among cattle and dogs from rural areas of
      all mesoregions of Parana, Brazil.

PMID- 20059848
TI  - [Seroprevalence, clinical and biochemical data of dogs naturally infected by
      Leishmania and phlebotominae sandfly fauna in an endemic area in Sao Luis Island,
      Maranhao State, Brazil].
AB  - The aim of this study was to determine the seroprevalence, clinical and
      biochemical profile of Leishmania chagasi infection in dogs naturally infected
      and identify the phlebotominae fauna in an endemic area of Sao Luis Island. In
      this present study, 62 household mongrel dogs were sampled for antibodies anti
      Leishmania. The seroprevalence was 51.61%. In the clinical evaluation, 36.68%
      dogs were symptomatic, 38.41% were oligosymptomatic and 26.13% were asymptomatic.
      The most frequent signs were onychogryphosis and lymphadenomegaly. In 29.41%
      animals were observed anemia. In the biochemical analysis hepatic function showed
      changes in relation to alaninoaminotransferase (ALT) and aspartato
      aminotransferase (AST). Urea values were higher than the references ones for
      canine specie. The following phlebotominae sandflies were identified: Lutzomyia
      longipalpis (86.9%), L. evandroi (9.6%), L. choti (2.1%), L. umbratilis (0.7%) e
      L. whitmani (0.7%).

PMID- 20059849
TI  - [Ovine abortion associated with toxoplasmosis: serological, anatomo-pathological
      and immunohistochemistry characterization].
AB  - Ovine toxoplasmosis is a major cause of abortion and placentitis. Lambs with
      congenital infection are born with encephalitis. Abortions occurred between May
      and August 2006 in an estate in Tres Palmeiras, southern Brazil. This study aimed
      to assess the frequency of abortion associated with toxoplasmosis among ewes in
      southern Brazil using indirect hemagglutination and pathoanatomical and
      immunohistochemical analyses. Blood samples were collected from nine animals for
      indirect hemagglutination. One fetus underwent necropsy and histopathological and
      immunohistochemical analyses. Three samples, one of which belonged to the
      necropsied animals mother, were positive on the serological test. The necropsy
      revealed pale foci in the liver, lungs with a marbled appearance, heart with
      severe pallor and brain and cerebellar congestion. Fragments of all organs were
      collected, fixed in 10% buffered formalin, processed, and stained with
      hematoxylin-eosin. Microscopically, there were cysts and tachyzoites in the brain
      in areas of malacia with microgliosis and lymphoplasmacytic infiltration,
      suggesting toxoplasmic encephalitis. There was also interstitial pneumonia,
      centrolobular necrosis with structures compatible with tachyzoites, focal
      lymphocytic myocarditis and acute tubular nephrosis. The immunohistochemical test
      was positive for Toxoplasma gondii. The results allowed diagnosing the ovine
      toxoplasmosis.

PMID- 20059850
TI  - [Importance of the handling in criptosporidiosis in sheep rearing].
AB  - With the objective to verify which are the risk factors in ovine
      cryptosporidiosis, 130 ovine fecal samples were collected in ten farms in Campos
      dos Goytacazes and Macae and analyzed using the modified Ziehl-Neelsen technique.
      Hygiene, breeding system, clinic alteration, veterinary assistance and source of
      water which were furnished to the animals were analyzed by chi2 Test and Fisher
      Exact Test, with Yates correction (when it was necessary) and 95% of confidence
      interval. Oocysts were observed in 47% of the farms. Clinic alteration as
      anorexia, apathy and diarrhea were not associated with cryptosporidiosis,
      however, due to a significative risk factors connected with animals breeding
      explained that the ovine handling is determinant in the presence of oocysts in
      ovine feces.

PMID- 20059851
TI  - Interleukin-12 response to NcSRS2 immunization of BALB/c mice against Neospora
      caninum.
AB  - The apicomplexan parasite Neospora caninum can cause abortions and is recognized
      as an important causative agent responsible for economic and reproductive losses
      in the cattle industry. Humoral immune response was investigated in BALB/c mice
      by using recombinant NcSRS2 expressed in Escherichia coli as polyhistidine-tagged
      fusion proteins. NcSRS2 is the major immunodominant tachyzoite surface antigen of
      N. caninum. Separate groups of female BALB/c mice were infected subcutaneously
      with (P) PBS, (N) recNcSRS2, (NIL) recNcSRS2 plus interleukin-12 or (NF)
      recNcSRS2, in Freunds adjuvant. Serological analysis showed that the antibodies
      produced by immunization recognized native protein from N. caninum tachyzoites
      and that, 14 days after the initial immunization, NcSRS2-specific antibodies were
      present in all sera tested from the groups N, NIL and NF. NcSRS2 with Freuds
      adjuvant led to a stronger immune response, as measured by IgG1 and IgG2a levels,
      than did other formulations (NF > NIL > N > P; p < 0.001), with a Th2 bias. The
      results corroborate the potential use of recombinant protein NcSRS2 as a vaccine
      aimed at reducing congenital transmission. Further studies are required to
      identify new adjuvants capable of improving the induction of Th1 immune response.

PMID- 20059852
TI  - [Malaricide activity of the quercetin in Gallus gallus L., 1758 immunocompromised
      infected by Plasmodium (Bennettinia) juxtanucleare Versiani and Gomes, 1941].
AB  - The aim of this study was comparatively to evaluate the malaricide activity of
      the quercetin to the action of the chloroquine in Gallus gallus experimentally
      infected for Plasmodium juxtanucleare and immunocompromised. Thirty- four hens
      had been used, previously infected for P. juxtanucleare and immunocompromised by
      the administration of 26 mg/kg of metilprednisolon 40mg/ml in the pectoral
      muscle. These had been divided in three groups: 1- control, 2- treated with
      chloroquine and 3- with quercetin. The administration of substances occurred way
      gavagem to four consecutive days. The malaricide action of the drugs was
      evaluated in agreement the parasitemia for P. juxtanucleare in blood smears,
      during 30 days after the infection. The groups that had received treatment with
      chloroquine and quercetin had presented significant reduction (p < 0,01 in both)
      of the parasitaemia comparative to the group control, it suggesting that the
      drugs had acted as malaricide in the infection for P. juxtanucleare.

PMID- 20059853
TI  - [Swine cryptosporidiosis related to production systems in the state of Rio de
      Janeiro].
AB  - The purpose of this study was to verify the prevalence of cryptosporidiosis in
      swine farms of familiar and technical production systems, located in the North
      and Northwest Regions of the State of Rio de Janeiro. A total of 103 fecal
      samples of different swines were collected, proceeding from 10 farms, of which
      five were familiar and five technical. For the diagnosis, the modified
      concentration by sedimentation technique with posterior staining by modified
      Ziehl-Neelsen was used. Forty and 29.3% of prevalence were observed in the
      familiar and technical farms respectively, and they were not statistically
      different. The parasitism occurs in both production systems, probably due to an
      absence of previous diagnosis of the illness. After morfometric and morphological
      analysis and statistical study of correlation of the 87 oocysts found, it was
      suggested that exists more than one species of Cryptosporidium spread in the
      properties, and they are common to each of the production systems. This
      hypothesis needs to be confirmed through studies of molecular biology, to
      characterize the species.

PMID- 20059854
TI  - [Oocysts from Cryptosporidium spp. isolated from cattle: pleomorfism in
      relationship to diagnosis methodology].
AB  - The aim of this study was to analyze the pleomorfism of Cryptosporidium spp.
      oocysts isolated from calves feces throughout the comparison of two diagnostic
      techniques. One hundred of cattle feces were collected and the samples were
      submitted to both flotation sucrose centrifugation and to Ziehl-Neelsen modified
      tests. The results obtained showed a statistically significant reduction on the
      size of the Cryptosporidium oocysts observed through Ziehl-Neelsen technique when
      compared to the flotation sucrose centrifugation technique, and that the
      difference on the diameter of the oocysts suggests the there were different
      species of Cryptosporidium circulating in the animals analyzed.

PMID- 20059855
TI  - [First notification of Eimeria bareillyi (Apicomplexa: Eimeridae) in feces of
      buffalo calves (Bubalus bubalis) naturally infected in Minas Gerais, Brazil].
AB  - In this study the evolution of Eimeriosis in naturally infected calves was
      analyzed during 23 days starting at birth. The specie E. bareillyi was first
      identified in feces culture. Later other species of Eimeria already described in
      water buffalo were identified. The animals which died were submitted to necropsy,
      revealing macroscopic lesions in the ileum region. Histological analyses of the
      ileum region showed acute necrotic enteritis and the presence of Eimeria sp. in
      different developmental stages. Early infection by this parasite could be
      responsible for a secondary bacterial infection trough the intestinal lesions.
      The utilization of prophylactic medication and the therapeutic treatment of
      clinical Coccidiosis in water buffalo calves are necessary to their satisfactory
      development and surveillance.

PMID- 20059856
TI  - [Occurrence of Cryptosporidium spp. in a dairy cattle herd from Cacapava
      Municipality, Sao Paulo State, Brazil].
AB  - Occurrence of Cryptosporidium spp. was investigated in a Brazilian dairy farm
      over the course of 1 year. Cattle of different aged were employed and divided
      into seven groups: 0-2 months; 2-4 months; 4-6 months; 6- 10 months; 10-16
      months; 16-24 months; > 24 months. Fecal samples were collected from a total of
      849 animals in six times. These samples were evaluated by centrifugal flotation
      method using a sucrose solution. Herd occurrence for C. parvum was 0.6%, varied
      by month of sample collection from 0 to 1.4%. The highest frequency of C. parvum
      was found in animals 0-2 months old with oocysts in 3 of the 61 samples (4.9%).
      Herd occurrence for C. andersoni was 0.1%, varied by month of sample collection
      from 0 to 0.7%. Only one cow was found infected for C. andersoni.

PMID- 20059857
TI  - [Relative risk of infection of parasites from genus Cryptosporidium in cattle in
      North of Rio de Janeiro State, Brazil].
AB  - The aim of the study was to detect Cryptosporidium oocysts in calves feces
      throughout North of Rio de Janeiro State, Brazil, as well as to examine the risk
      factors involved in the animals infection. One hundred young calves on 13 dairy
      farms were analyzed for oocyst excretion. The samples were submitted to Ritchie
      and Ziehl-Neelsen modified tests, and the observation of the oocysts was made by
      using the optical microscope. The results obtained showed that Cryptosporidium
      was detected in 61% of the animals. Statistical analysis of the risk factors
      revealed that only three of them demonstrated a significant influence for
      infection: Animals bred under technical systems such as the use of milking
      equipment, milking cooler and farms that have water trough were more likely to be
      infected with the protozoan.

PMID- 20059858
TI  - [Action of beta-glucan in pigs experimentally infected with Toxoplasma gondii
      tachyzoites].
AB  - The present study tested the action of Beta-glucan in swine experimentally
      infected with tachyzoites of Toxoplasma gondii. The experiment design used 8
      mixed breed pigs (21 days) divided into three groups: G1 (Beta-glucan treated and
      infected, n = 3), G2 (untreated and infected, n = 3), and G3 (untreated
      uninfected, n = 2). The G1 animals were treated with 1g of Beta-glucan by
      intramuscularly route at days 0, 14, and 28 before experimental infection, while
      the other groups (G2 and G3) received only saline. The G1 and G2 were infected
      with viable tachyzoites (107) of the RH strain at day 35 of experiment. The
      parasitemy was determined by mouse bioassay and PCR from whole blood of each
      swine, obtained at days 3, 7, 14, 21, 31, 39, 47 e 69 post infections. The
      antibody levels of serum, aqueous and vitreous humor were measured by indirect
      immunofluorescence assay (IFA); a title >/= 64 was considered as positive. There
      were differences in the hematocrit, hemoglobin, plasmatic proteins, and
      eosinophils values between groups (P< 0.05). The swine of G1 and G2 serum
      converted 7 days post infection, and the highest title observed was 1024 in two
      pigs. Samples of aqueous and vitreous humor did not show antibodies against T.
      gondii. Parasite was detected of whole blood on days 3, 14, 31, 39, and 47 in two
      animals from G1, and three animals from G2. There were no differences between PCR
      and mouse bioassay. Animals from G3 remained without parasitemy by both PCR and
      bioassay throughout the experiment. The use of Beta-glucan, as was used here, was
      not protective for pigs against T. gondii tachyzoites acute infection.
      Additionally, the lineage of RH strain showed nonpersistent for pigs (muscles and
      retina) 69 days after infection.

PMID- 20059859
TI  - [Risk factors of Cryptosporidium sp. infection in household dogs of Campos dos
      Goytacazes City on Rio de Janeiro State, Brazil].
AB  - Cryptosporidium sp. is an opportunistic protozoan parasite that may infect
      animals and humans, causing asymptomatic to severe intestinal infections,
      according to the immunological response of the hosts. The present work had the
      objective to determine the risk factors involved on Cryptosporidium sp. infection
      in dogs from Campos dos Goytacazes City on Rio de Janeiro State; and the
      frequency of this protozoan. Independent of sex, age, consistency and health of
      dogs, 200 feces samples were analyzed. Data were obtained using a questionnaire
      with the dogs owners. Feces were analyzed with an optical microscope after the
      concentration by modified Ritchie technique and coloring with the modified Ziehl
      Neelsen technique. Association tests through c2 and multiple logistic regression
      analysis were made. Among the 200 dogs analyzed, 90 (45%) showed oocysts of
      Cryptosporidium genus in the feces. The conclusion was that the occurrence of
      asymptomatic cryptosporidiosis in dogs from the City of Campos dos Goytacazes is
      high. The risk factors involved are the social level of the owner, presence of
      cats and sporadic stage of vomiting and diarrhea. The final model detected the
      risk factors by social level, other animals, regions of the city, kind of
      residence, sporadic stage of vomiting and diarrhea.

PMID- 20059860
TI  - [Seroprevalence of antibodies anti-Neospora caninum and anti-Toxoplasma gondii in
      captive wild canids].
AB  - Neosporosis is considered one of the main cause of abortion in dairy cattle in
      the world. The prevalence of Neospora caninum in wild species has been studied
      since the coyote (Canis latrans), a North American wild canid specie was
      discovered as definitive host of this parasite. The aim of the present study was
      to determine the serum prevalence of N. caninum and T. gondii in wild native
      canids species from Brazil. Serum samples of 25 crab-eating dogs (Cerdocyon
      thous), five pampas fox (Lycalopex gymnocercus), six bush dogs (Speothos
      venaticus) e 14 maned wolves (Chrysocyon brachyurus) were tested. The animals
      were from zoos and sanctuaries from the states of Parana, Santa Catarina, Rio de
      Janeiro and the Federal District. The total prevalence obtained for N. caninum
      was 36% (18/50) and for T. gondii was 40% (20/50). The present study demonstrated
      for the first time the presence of antibodies to N. caninum in bush dogs and the
      prevalence found was 33,3% (2/6). This study showed the presence of these
      protozoans in captive wild canids species and to alert about possible
      contamination sources.

PMID- 20059861
TI  - [Achatina fulica Bowdich (1822) a new host of Cryptosporidium (Apicomplexa,
      Cryptosporidiidae) species].
AB  - With the objective of isolate Cryptosporidium spp. in Achatina fulica s feces, 50
      mollusks were collected in nine neighborhoods of the municipal of Campos dos
      Goytacazes, RJ to the observation of oocysts in feces. The snails were put in
      individuals containers and fed with water and green vegetables ad libitum until
      be collected a gram of feces per animal. The samples were conditioned in tubes
      with formalin 10% and later smear of feces were made and dyed by Ziechl-Neelsen
      modified technique. Of the 50 samples examined, 26 (52%) were positive for the
      presence of oocysts of Cryptosporidium spp. The morphology and morphometry of the
      oocysts showed that are a great morphologic variability. Considering the obtained
      results, the mollusk Achatina fulica is a host of Cryptosporidium species and can
      participate in the epidemic chain of the cryptosporidiosis.

PMID- 20059862
TI  - [Occurrence and molecular characterization of Babesia species in a canine
      hospital population in the Londrina Region, Parana State, Brazil].
AB  - Canine babesiosis is a worldwide disease caused by the protozoan of Babesia
      genus. Babesia canis and B. gibsoni are both species that naturally infect dogs.
      The objective of this study was to evaluate the infection of Babesia species in
      dogs attended at the Londrina State University Veterinary Teaching Hospital (HV
      UEL). It was selected 282 dogs seen at the Londrina State University Veterinary
      Teaching Hospital (HV-UEL) between April of 2005 and May of 2006. They presented
      anemia (Packed Cell Volume<25%), thrombocytopenia (Platelet count <150000/mm3),
      leukopenia (White blood cell count<5000/mm3) or a combination of two or three of
      these alterations at the moment of the consultation. The presence of Babesia sp
      was determined by the amplification of a specific fragment of DNA of the Babesia
      genus by PCR. Microscopic examination of Giemsa-stained blood smears detected 38
      (13.5%) positive samples against 105 identified by PCR from 282 dogs. The
      positive samples were submitted to PCR-RFLP by Hinf I that allows distinguishing
      the species of B. canis vogeli and B. gibsoni. From 282 dogs, Babesia sp
      infection was identified in 105 (37.2%). From these 105 positive samples, the PCR
      RFLP identified 66 (23.4%) samples with a profile compatible to B. canis vogeli
      and 39 (13, 8%) to B. gibsoni. As conclusions, the results obtained allow to
      affirm that the babesiose is an important differential for dogs that present
      anemia, leukopenia and thrombocytopenia and, B. canis vogeli is the subspecies
      that is present in the most of the cases of babesiose in the population of dogs
      studied and, that B. gibsoni is also present causing babesiosis in dogs of the
      Londrina region, Parana State, Brazil.

PMID- 20059863
TI  - [Pharmacologically immunosuppressed mice as a model for study of opportunistic
      parasite infections].
AB  - Immunodeficient animals are important research models for studies in
      parasitology, oncology and immunology. Immunosuppressive drugs have been
      experimentally used to obtain a state of immunodeficiency in mice. This
      investigation aimed to quantify the circulating T and B cells of mice treated
      with the immunosuppressive agents dexamethasone (Dx), cyclosporine (CsA) and
      cyclophosphamide (CY), as well as to observe the behaviour of lymphocytic
      populations in the spleen of these animals. Blood samples were collected for
      counting the total peripheral blood leukocytes and T and B lymphocytes using flow
      cytometry. Total leukocytes of mice treated with the three drugs during all study
      showed a significant decrease when compared to the results of the control group.
      The proportion of B and T lymphocytes from the treated animals also decreased
      significantly. Spleen sections revealed a moderate decrease in the cellularity of
      the white pulp and the development of lymphocyte apoptosis in mice from groups
      treated with CY and Dx. Results showed that the proposed experimental models
      demonstrated to be suitable for studies of murine immunodeficiency.

PMID- 20059864
TI  - [Relationship between companion animals and intestinal parasites in children at
      municipality of Seropedica, RJ].
AB  - Several parasitic zoonoses are associated to the human and companion animals,
      mainly dogs and cats. The present work aimed to analyze the relationship of
      parasites in children at the Center of Integral Attention to the Child Paulo
      Dacorso Filho and their companion animals where to verify the relationship of
      positive children for some parasites, which got in contact with infected animals.
      In a total of 64 fecal samples, they were consisted by 46 childrens fecal samples
      and 21 of their companion animals, being 18 from dogs and 3 from cats. Those were
      analyzed by using the techniques of centrifugal-flotation in brilliant field and
      staining by modified Ziehl-Neelsen to determine Cryptosporidium spp. oocysts. Of
      the childrens samples, 91% were positive for the genus Cryptosporidium, of those
      13 samples; they were also in association to Giardia intestinallis, two to
      Ascaris lumbricoides, two to Trichuris trichiura and one to Endolimax nana only.
      Of the dogs samples, 94.44% were positive where Cryptosporidium spp. was observed
      in 94.44% of them, Ancylostoma spp. In 50%, Cystoisospora canis in 5.55% and
      Toxocara canis in 11.11%. The parasite that was common among children and animals
      belongs to genus Cryptoporidium. However, most of the positive children for
      Cryptosporidium spp., did not get in contact with animals.

PMID- 20059865
TI  - [Risk factors and prevalence of antibodies anti-Neospora caninum in urban and
      rural dogs from Rio Grande do Sul, Brazil].
AB  - Serum samples from 339 dogs from rural (beef and dairy farms) and urban areas of
      Municipality of Pelotas, RS, were tested by indirect fluorescent antibody test to
      verify the presence of antibodies anti-Neospora caninum. Data from dogs took part
      of an epidemiologic questionnaire to identify possible risk factors associated
      with the seropositivity. Antibodies anti-N. caninum were found 15.6% (53/339) of
      serum samples, with 5.5% (6/109) of positive dogs from urban area and 20.4%
      (47/230) from rural area. The analysis multivariate of the risk factors in showed
      that rural dogs have 3.5 times more chance of contact with the parasite than
      urban dogs. Dogs with more than 3-years old have a greater risk (OD = 4.1) to be
      positive for N. caninum than dogs with less than 3-years. Rural dogs from beef
      farms presented greater risk (OD = 2.8) to be positive when compared with dogs
      from dairy farms. Seropositivity rate increased 2.2 times in farms which the
      carcasses of dead animals and aborted fetus were not appropriately removed. N.
      caninum is present in the southern region of the Rio Grande do Sul, infecting
      urban and rural dogs.

PMID- 20059866
TI  - [Occurrence of infection Leishmania spp. and Toxoplasma gondii in monkeys (Cebus
      apella) from Campo Grande, MS].
AB  - The aim of this study was research antibodies from infection by Leishmania spp.
      and Toxoplasma gondii in nonhuman primates (HNP) and compare the techniques of
      reaction of Indirect immunofluorescence (IFAT) and Modified Agglutination Test
      (MAT) for the search of T. gondii. Fourteen adults monkeys (Cebus apella) were
      examined, from the Centre for Rehabilitation of Wild Animals (CRAS) from Campo
      Grande, MS. The research of anti- Leishmania spp. was performed by IFAT and
      research of anti-T. gondii was held by IFAT and MAT. No sample was positive for
      the detection of anti-Leishmania spp. We found a prevalence of 28.7% (4/14) by
      IFAT and 30.8% (4/ 13) by MAT in search of anti-T. gondii. The techniques
      presented agreement when used for the detection of anti-T. gondii in the
      population studied. The presence of antibodies T. gondii may be related to the
      environment contaminated by oocysts of wild felines, by contact with the parasite
      by handling food, since they were offered fruit and raw meat or the invasion by
      birds and/or rodents, which may serve as prey by monkeys.

PMID- 20059867
TI  - [Epidemiologic survey of Neospora caninum in bovines of rural settlements in
      Corumba, MS].
AB  - Neospora caninum, is an obligate intracellular parasite, can infect domestic and
      wild dogs, equines and ruminants. It was described in 1988, and its economic
      importance is attributed to costs of abortion, the value of the fetuses,
      artificial insemination and coverage, the decrease in milk production, the
      increase in the disposal and replacement of animals. In four rural settlements of
      the municipality of Corumba, MS (Mato Grande, Paiolzinho, Taquaral and
      Tamarineiro) was used a combination of qualitative methodologies in 37 semi
      structured interviews and group dynamics for analysis with participatory rural
      producers of 657 animals were raised health problems related to production and
      disease of the herd, and possible variables of risk for the presence of
      neosporosis. This study evaluated in 392 samples of bovine serum from the
      settlements of Corumba, the presence of animals seropositive for N. caninum, to
      indirect fluorescence antibody test (IFAT), and prevalence weighted for neospora
      was 9.17%, ranging from 4.96% to 13.38%. The survey of variables of risk to
      Neospora investigated in the interviews did not indicate any risk factor for the
      disease.

PMID- 20059868
TI  - [Seroepidemiological studies on Babesia equi in horses from the State of Rio
      Grande do Sul determined by indirect immunoflourecence test and Elisa].
AB  - This research was performed to study the prevalence of antibodies against Babesia
      equi in horses of the northern region of Rio Grande do Sul state, using ELISA and
      indirect immunofluorescence antibody test (IFA). The total sera sample was 380,
      this number was considered as statistically representative of the population, as
      determined by mathematical model. The prevalence of B. equi was 31.6% and 35.8%
      by ELISA and IFA, respectively. The concordance between the assays was 0.87
      (indices kappa), which is considered an optimal result. The results did not show
      any significant statistical difference (P < 0.05) between sex, age and horses
      breed. The results of this study allowed the characterization of the northern
      region of Rio Grande do Sul as an instable enzootic area for B. equi, which
      indicates a potential risk of economic losses caused by babesiosis outbreaks,
      especially for sensible horses from non enzootic areas or even born is the
      studied region.

PMID- 20059869
TI  - [Occurrence of Cryptosporidium spp. oocysts (Apicomplexa, Cryptosporidiidae) in
      ostriches, Struthio camelus L., 1758 (Aves, Struthionidae) reared in North and
      Lowered Coastline regions of the state of Rio de Janeiro, Brazil].
AB  - The aim of this research was to determine the prevalence of Cryptosporidium spp.
      in ostriches reared in the state of Rio de Janeiro. The diagnosis of oocysts of
      Cryptosporidium spp. in the feces of 77 ostriches was done by modified Ziehl
      Neelsen technique. The occurrence was observed in 44.4% of the examined animals.
      However, in a property 100% of the ostriches shed oocysts in their feces. Oocysts
      was subspherical in shape with 6.33 +/- 1.27 (4.31-9.63) by 5.90 +/- 1.18 (4.07
      9.42) mm and shape index of 1.07 +/- 0.05 (1.00-1.29). Was verified a high
      occurrence of oocysts elimination. In spite was observed a uniform distribution
      of the oocysts measurements in the regression line (R2 = 0.9438) accentuated
      difference was evidenced in the morphometry of the oocysts, that suggests that
      more of a species of Cryptosporidium are parasitizing these birds.

PMID- 20059870
TI  - First report of Tyzzeria parvula (Kotlan, 1933) Klimes, 1963 (Apicomplexa:
      Eimeriidae), in swan goose Anser cygnoides L., 1758, in Brazil.
AB  - This is the first description of Tyzzeria parvula from the swan goose (Anser
      cygnoides) in the State of Rio de Janeiro, Brazil. Fecal samples were collected
      from 15 swan geese, but only four of them shed oocysts in feces. After
      sporulation, the oocysts were spherical to sub-spherical, and measured 12.4 +/-
      1.0 (11-15) x 10.4 +/- 0.8 mum (8-12). They presented a shape index of 1.2 (1.0
      1.4), with a bi-layered wall that was 0.7 +/- 0.1 mum (0.6-0.8) thick. The outer
      side was smooth and colorless, while the inner side was pale greenish. Micropyles
      and polar granules were absent. The residuum sometimes formed a mass of spherules
      and granules and, at other times, was dispersed. Sporozoites had one rounded end
      and the other end was fine and slightly curved.

PMID- 20059871
TI  - Balantidium sp. in ostriches (Struthio camelus L., 1758) in the State of Rio de
      Janeiro, Brazil.
AB  - The aim of this work was report for the first time the occurrence of Balantidium
      sp. in ostriches reared in Rio de Janeiro state, Brazil. Feces samples from 82
      ostriches were examined by the Ziehl-Neelsen technique and morphometric analyses
      were made of the cysts. The data were compared by a simple linear regression
      analysis. The cysts found ranged in size from 60.39 by 34.62 mm and 59.13 by
      33.92 m in diameters. The spherical shape was confirmed by observing the shape
      index of 1.05 and r = 0.9630, which suggested there were cysts of different sizes
      with similar shapes. In spite of polymorphism, cysts measurements were uniform in
      their distribution, evidencing the possibility of a single species (R2 = 0.9274).
      The cysts were morphologically indistinguishable from the Balantidium sp. cysts
      already reported in ostrich feces or B. coli. This is the first report of
      parasitism by Balantidium sp. in ostriches in Brazil. In spite of the high
      Balantidium sp. frequency, no clinical sign was observed.

PMID- 20059872
TI  - [Evaluation of small intestine and mesenteric lymph nodes of dogs (Canis
      familiaris) experimentally infected by Sarcocystis cruzi (Hasselman, 1923)
      Wenyon, 1926 (Apicomplexa: Sarcocystidae)].
AB  - Species of the genus Sarcocystis are considered as important parasites of
      domestic animals. Dogs are considered as definitive host for a variety species of
      Sarcocystis, when they fed on intermediated host tissues cysts shed sporocysts in
      their feces. Grinded bovine cardiac muscles, positive for Sarcocystis cruzi was
      given to two puppies free of coccidia. Both animals shed sporocysts in their
      feces at 12 days after infection (DAI). These sporocysts measured 17.44 +/- 0.82
      11.60 +/- 0.66 mum with shape index of 1.50 +/- 0.05. At 23 DAI, these animals
      were posted and samples of the small intestine, such as: duodenum, jejune, ileum
      and mesenteric lymph nodes were collected. In the analysis of small intestine,
      sporocysts were observed under de mucosa and they were characterized by
      sporulated sporocysts with sporozoites. Lesions were consisted of discrete edema
      and plasmocytic cells infiltrations which they were associated to a minimal
      inflammatory reaction in the presence of parasitic stages. On the other hand,
      sporocysts were observed at the cortical region near of lymphatic vessels
      adjacent to mesenteric lymph nodes capsule. It indicated the involvement of the
      lymphatic vessels in the sporocysts dispersion in the dog mesenteric lymph nodes.

PMID- 20059873
TI  - [Seroprevalence and month dynamic of Neospora sp. antibodies in pregnant mares].
AB  - In order to evaluate the seroprevalence and the dynamic of anti-Neospora
      antibodies in pregnant mares, serum samples from 14 animals in the 8th, 9th, 10th
      and 11th month of pregnancy were analyzed using indirect immunofluorescense
      technique. Samples diluted 1:50 showed higher seroprevalence on the 8th month
      (57%) and higher seropositive conversion on the 10th month. 85,7% of the mares
      were positive for Neospora sp. on at least one month of pregnancy, and seven from
      that total were positive on the 11th month, three of which showed the highest
      titles of 1:200 and 1:400. For the samples diluted 1:100 the highest
      seroprevalence was found on the 11th month (29%) and the 10th month showed the
      highest seropositive conversion. 64% of the mares were seropositive on at least
      one month of pregnancy, four of them on the 11th month. There was a marked
      variation for the serum levels of anti-Neospora antibodies indicating the need to
      test pregnant mares between the 8th and the 11th month of pregnancy for
      neosporosis in order to monitor the sanitary condition of these animals.

PMID- 20059874
TI  - [Canine visceral leishmaniasis in dog from Caldas Novas, Goias].
AB  - The objective of the present work was to describe a visceral case of
      leishmaniasis in a dog from Caldas Novas, GO, region until then considered as a
      disease free area. The animal, attended in the Veterinarian Hospital of the
      Federal University of Goias, presented loss of weight, alopecic area of irregular
      format at the nasal back, onicogrifosis, atrophy of the heads muscles and failure
      of the right popliteus lymphonode. For the laboratorial diagnosis, samples were
      collected by biopsy from the complete skin of the auricular region, by punsion
      from the popliteus lymphonode for preparation of Giemsa stained blades and 5 mL
      of the blood were also collected for serum diagnosis. The direct microscopy
      revealed, from the evaluation of the imprint obtained from the skin fragment and
      from the squash of the inhaled lymphonode, great amount of amastigoste forms of
      Leishmania in the cytoplasm of macrophages. Based on the clinical presentation,
      on the parasitologic and on the serology examination of the samples, we concluded
      the exams with the diagnosis of calazar disease.

PMID- 20059875
TI  - Sarcocystis lindsayi-like (Apicomplexa: Sarcocystinae) of the opossum (Didelphis
      aurita) from Southeastern Brazil.
AB  - Sporocysts of Sarcocystis were obtained from intestinal scrapings of three out of
      five opossums (Didelphis aurita) trapped in the southeastern region, of the State
      of Rio de Janeiro, Brazil. Fifteen caged budgerigars (Melopsittacus undulatus)
      received, orally, twenty-six sporocysts in 500 mL PBS, but only five belonging to
      one of the groups developed clinical signs, that consisted of anorexia, lethargy,
      ruffled feathers and dyspnoea, and parasitism in tissues. Two of the five
      budgerigars died on the 25th and 29th days after infection (DAI). The other three
      budgerigars were posted on the 30th DAI. In all the five infected birds were
      observed meronts in the capillaries of the lungs and cysts in muscles, mainly in
      the tongue and legs.

PMID- 20059876
TI  - [Continued vigilance actions, dogs role as sentinel animal to toxoplasmosis].
AB  - Toxoplasmosis is a worldwide zoonosis caused by Toxoplasma gondii and its
      definitive host is the domestic and wild felids infecting human beings and other
      warmblooded animals. Dogs are considered a potential risk on the transmission due
      they can mechanically transmit oocysts to man. In this study, a retrospective
      analysis of toxoplasmic infection in dog serum samples sent to Servico de
      Diagnostico de Zoonoses/FMVZ-UNESP/Botucatu, SP, in the period of 1998 to 2007
      was performed. During this period 1097 serum samples were analyzed by the
      indirect fluorescent antibody test (IFAT), with 299 (27.25%) positive. The most
      frequent titer was 16 (42.80%), followed by 64 (37.79%). The results indicate
      that T.gondii is distributed in the environment showing the role of the dog as
      sentinel animal to toxoplasmosis to monitor public health actions to the control
      of this zoonosis.

PMID- 20059877
TI  - [Molecular diagnostic of congenital babesiosis in neonates foals from State of
      Rio de Janeiro, Brazil].
AB  - The aim of this study was to demonstrate, through nested PCR (nPCR) method, the
      occurrence of congenital babesiosis in two foals born of carrier mares. All mares
      were positive for T. equi based in visualization of intraerytrocytic parasites in
      blood smears, in indirect fluorescent antibody test (IFAT) and nPCR reactions.
      Just one mare was nPCR-positive for B. caballi. After the birth, all foals
      presented nPCR-positive for T. equi, while just one foal presented nPCR-positive
      for B. caballi. The present study prove the occurrence of congenital babesiosis
      in new-born foals, however, new studies are necessary to elucidate if the
      infection occur for transplacental transmission or in parturition moment.

PMID- 20059878
TI  - [Evaluation of different diagnostic techniques for oocysts of Cryptosporidium
      baileyi in broiler chickens (Gallus gallus domesticus) fecal samples].
AB  - The objective of this work is to evaluate different diagnostic techniques for
      Cryptosporidium baileyi oocysts in broiler chickens fecal samples infected
      naturally. So 90 samples were collected and conditioned in bottles with 10%
      formaline and submitted to Sheater s technique in bright field. Besides it,
      duplicate smears of the same samples were stained by safranin-methylene blue and
      modified Ziehl-Neelsen. Among the staining techniques, modified Ziehl-Neelsen got
      better result in the detention of C. baileyi oocysts in comparison to safranin
      methylene blue. In spite of no significant differences among these techniques in
      the diagnosis of C. baileyi oocysts of fecal samples, bright field presented
      better results.

PMID- 20059879
TI  - Prenatal and perinatal management of preterm labour.
AB  - New knowledge of the pathophysiology of premature birth enables us to introduce
      new approaches in prenatal care as well as the management of premature delivery.
      These apply for the patients with subclinical risk factors, particularly with
      thrombophilias, chronic infections or other latent chronic infections. The peri-
      and pre-conceptional dispensarisation of these women might help reduce the
      development of premature delivery. Secondary prevention with the administration
      of gestagens is highly important for women with anamnestic or existing risk of
      premature delivery. During the underlying premature delivery, it is advisable to
      re-evaluate the significance of the administration of antibiotics and tocolytics
      as well as timing of corticoid dosage in the induction of foetal lung maturity.
      Using new diagnostic and therapeutic methods, the aim of present premature
      delivery management is to prolong the duration of pregnancy to the maximum with
      the lowest risk of the development of foetal inflammatory response possible and,
      therefore, with a low risk of long-term handicaps in children.

PMID- 20059880
TI  - Education in and the practice of dental public health in the United kingdom and
      Finland.
AB  - This paper describes and compares the education in and practice of dental public
      health in Finland and the United Kingdom. A brief introduction describes the
      populations of the two countries in terms of their geography, mean per capita,
      Gross Domestic Product (GDP), life expectancy, recent oral epidemiological data,
      oral health needs and the dental workforce. This is followed by a description of
      education in Dental Public Health in each country at undergraduate, postgraduate
      and continuing levels. The practice of Dental Public Health is then outlined. In
      both countries it includes: leadership and management of health organisations,
      teaching, training, research, advising and evaluating. A discussion follows. It
      considers the need for the provision of Dental Public Health at a time of
      changing oral health need and gives examples of problems that have arisen when
      such advice has not been sought or has been ignored. Finally, the paper considers
      how education in Dental Public Health could be developed to provide more flexible
      training whilst ensuring that the quality of knowledge and skills of specialists
      is maintained or improved.

PMID- 20059881
TI  - Microvascular Reactivity and Endothelial Function in Type 2 Diabetic Patients
      with Hyperlipidemia Treated with Simvastatin: 3-year Follow-up.
AB  - Aim of this study was to evaluate microvascular reactivity (MVR) by laser Doppler
      flowmetry in Type 2 diabetes mellitus (T2DM) with hyperlipidemia during three
      years of simvastatin treatment. Additionally, markers of endothelium and
      fibrinolysis were evaluated. Twenty patients with T2DM and hyperlipidemia were
      treated with 20 mg of simvastatin daily for 3 months, treatment was then
      interrupted for 3 months (wash-out) and again started and maintained continually
      up to total of 36 months of follow-up. Maximal perfusion (max), velocity of
      perfusion increase (max/t) and percent increase of perfusion compared to baseline
      (%) was measured during post-occlusive reactive hyperemia (PORH) and thermal
      hyperemia (TH). VCAM-1, ICAM-1, E-selectin and P-selectin were used as markers of
      endothelium, tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as
      markers of fibrinolysis. Baseline MVR in diabetic patients was comparable to
      controls. MVR decreased at months 3, 12, and 36 compared to baseline (PORHmax
      26+/-12, 35+/-17, 26+/-11 vs. 56+/-30 PU, p<0.05, THmax 67+/-19, 81+/-37, 58+/-24
      vs. 134+/-70 PU, p<0.01, PORHmax/t 2.0+/-1.4, 2.8+/-1.7, 1.9+/-1.3 vs. 7.7+/-7.4
      PU/s, p<0.05, THmax/t 1.1+/-0.6, 1.0+/-0.4, 0.7+/-0.4 vs. 1.5+/-0.7 PU/s, p<0.05.

PMID- 20059882
TI  - Synovial cysts of the lumbar facet joints: a retrospective magnetic resonance
      imaging study investigating their relation with degenerative spondylolisthesis.
AB  - Patients with synovial cysts of the facet joints were compared with patients with
      degenerative spondylolisthesis (DS), based on the magnetic resonance imaging
      (MRI) findings of their spondyloses. The lumbar MRI of 30 patients with DS (group
      1) 24 patients with synovial cysts of the facet joints (group 2) were studied.
      All patients were evaluated in terms of facet joint arthritis, disc degeneration,
      facet joint effusion, and the thickness of the flaval ligament. 54.1% of the
      patients with synovial cysts had associated DS. The mean grade of disc
      degeneration (2.43+/-0.50 and 2.13+/-0.68 in groups 1 and 2, respectively) and
      the mean thickness of the flaval ligament (3.20+/-1.22 mm and 3.83+/-1.46 mm in
      groups 1 and 2, respectively) did not differ between the groups (p=0.093 and
      p=0.097). The mean grade of facet joint osteoarthritis (2.53+/-0.51 and 2.08+/
      0.72 in groups 1 and 2, respectively) was significantly higher in group 1
      (p=0.18). The co-existance of synovial effusion was significantly higher in cases
      with synovial cysts. (p=0.008). Synovial cysts are associated with DS and facet
      joint osteoarthritis. The presence of synovial effusion and the high degree of
      disc degeneration are prominent features in patients with synovial cysts.
      Although osteoarthritis and DS are highly concomitant with facet joint synovial
      cysts, both conditions do not invariably lead to a cyst formation.

PMID- 20059884
TI  - Overdenture - implants versus teeth - quality of life and objective therapy
      evaluation.
AB  - An overdenture is a complete or removable partial denture that has one or more
      tooth roots or implants to provide a support. The study compares two types of
      prosthodontic treatment - overdenture supported by remained own teeth with ball
      attachments and that held by implants. The cohort of 35 patients (recall from 1
      to 5 years) was evaluated. When subjectively and objectively assessed no
      significant difference between both groups was observed.

PMID- 20059883
TI  - Expression of erythropoietin and angiogenic growth factors following inner ear
      injury of newborn rats.
AB  - Recently we have demonstrated that recombinant human erythropoietin (EPO)
      protects neurosensory hair cells in the organotypic culture of the organ of Corti
      by reducing apoptosis and necrosis. In the present study, we tested the
      hypothesis that EPO may be involved in reparative angiogenesis. We analyzed in
      parallel the endogenous erythropoietin (Epo) mRNA expression and that of Epo
      receptor (Epor) and of genes associated with angiogenesis in the organ of Corti,
      the modiolus and the stria vascularis using real time reverse transcription
      polymerase chain reaction and microarray. We compared the expression levels of
      freshly prepared tissue (control) and tissue cultured for 24 h under normoxia or
      hypoxia. The basal expression of Epo- and Epor mRNA in controls of all regions
      was very low. However, after 24 h in culture, a 20-100 fold increase of these two
      transcripts was measured. In culture, the vascular endothelial growth factor and
      the Cxcr4 (the receptor for the stromal cell-derived factor-1, Sdf-1) mRNA
      levels, were found to be increased and the Sdf-1 mRNA level to be decreased.
      Changes in mRNA expression occurred in all pathways activated in non-erythroid
      cells by the application of EPO (phosphoinositide 3-kinase/serine-threonine
      protein kinase B, Janus-type protein tyrosine kinase 2/signal transducer and
      activator of transcription 3, and the mitogen activated protein kinase). These
      data suggest that the neuroprotective effect of EPO may include at least two
      molecular events, the decrease of hair cell death rate and the induction of
      angiogenic genes.

PMID- 20059885
TI  - Is bone mineral density measurements correlated with facet joint orientation? A
      dual energy X-ray absorptiometry study.
AB  - We aimed to study correlation between bone mineral density (BMD) and facet joint
      orientation in normal, osteopenic and osteoporotic patients. The correlation
      between more sagittally oriented facet joint and facet joint osteoarthritis and
      spondylolisthesis was described previously. However, the correlation between
      facet joint orientation and its possible correlation with BMD measurements has
      not been evaluated. Our study is a primary effort to describe the correlation of
      BMD with facet joint orientation, which is important in terms of spinal
      biomechanics. Thirty-seven patients who had undergone both lumbar spinal Magnetic
      Resonance Imaging and Dual-energy X-ray absorptiometry were included in the
      study. Facet joint osteoarthritis and orientation were evaluated in five levels
      between L1-S1. For facet joint orientation, axial images were used. For grading
      of facet joint osteoarthritis the classification of Weishaupt and co-workers were
      used. Lumbar BMD was correlated with BMD of the hip. Facet orientation was
      similar among the 3 groups namely patients with normal BMD values, osteopenia and
      osteoporosis. Facet orientation was not correlated with lumbar BMD measurements.
      Facet joint orientation is not correlated with BMD measurements in our patient
      group without spondylolisthesis. Since spondylolisthesis has been demonstrated to
      alter BMD measurements, we suggest that spinal degenerative disease secondary to
      spondylolisthesis is the main entity leading to measurement errors.

PMID- 20059886
TI  - Smoking prevention at Prague basic schools.
AB  - Tobacco smoking is the most prevalent preventable cause of morbidity and
      mortality worldwide. Tobacco dependence is a paediatric disease: the majority of
      smokers light their first cigarette before they reach the age of 18. The paper
      evaluates anonymous questionnaires collected during 55 seminars at basic schools
      in Prague during 2006, where 776 students of the 3rd-9th classes took part.
      Lectors were specially trained medical students (4th and higher year of study)
      from three Medical Faculties in Prague, who additionally had experiences working
      as consultants of the Czech Quitline. The given structure of smoking prevention
      seminars is described. Almost half of children in the age of 8-15 years had some
      experience with smoking: 45.6% of girls (170/372) and a 47.9% of boys (189/394).
      Mean age of the first cigarette was 9.95 (SD 3.6) years. Those alarming data
      should lead to adoption of effective tobacco control measures in the society.

PMID- 20059887
TI  - [Application of the balanced scorecard for evaluating the training process].
AB  - Over the last 20 years systems for standardizing nursing care have been
      elaborated and refined. Such systems are widely employed in teaching and research
      but very little in clinical practice (Kautz D., et al., 2006) ) However, it would
      be useful to integrate these systems with synthetic descriptions of nursing
      intervention to improve our knowledge of "offer and demand" in this field
      (Jungher, 2006). It is no coincidence that these systems are used more in
      countries where the type of health system makes it necessary to quantify the
      contribution of each single health operator in the overall care procedure. The
      aim of the study was to assess the relevance of the different classifications ,
      considering them not only influenced by nursing but also to some degree
      influential.

PMID- 20059888
TI  - [Home care in lombardy region: comparative analysis of organizational models
      chosen by aziende sanitarie locali (local health centre) from the introduction of
      the social-sanitary voucher].
AB  - The growth of health request points out the necessity to answer in a different
      way to the social-sanitary needs of the population, in order to guarantee and
      organize services focused on the person's needs, which must be highly
      appropriated, timely, efficacious, and characterized by an efficient
      administration of the resources. The Lombardy Region, adopting these suggestions,
      through the regional law 31/97, reorganized the Regional Health-Care System,
      basing on two essential elements: the persons' centrality and their chance to
      chose among the existing types of treatments. Since July 1st, 2003 also the home
      care service of Aziende Sanitarie Locali (Local Health Centre) in Lombardy, has
      substantially modified the previous organization, introducing the social-sanitary
      voucher, that allowed the "weak" patients, to buy the integrated social-sanitary
      assistance services, done by professionally qualified people, directly from
      accreditated firm by Regional Health-Care Service. The purpose of the descriptive
      research is to know, after three years since the beginning of this process, the
      situation in the fifteen Aziende Sanitarie Locali of Lombardy Region, through the
      analysis and the comparison of the adopted organization models. The data
      collecting is based on three sources: contacts with Lombardy Region; delivery of
      a questionnaire-interview to all the Aziende Sanitarie Locali; internet
      consultation. From the data processing it is evident that, to an only model
      suggested by the Lombardy Region, the thirteen Aziende Sanitarie Locali that
      answered to the questionnaire, adopted a polyhedric organizational choices, that,
      of courses, affect the characteristics and the way to supply the service.

PMID- 20059889
TI  - [Instrument for evaluating autonomy of elderly patients in assuming oral
      medication].
AB  - The study deals with the problems facing elderly patients in rehabilitation
      structures having to autonomously assume oral medication. Often, elderly people
      who were previously capable of doing so, become confused and disoriented when
      admitted to rehabilitation. This may be due to physical or mental deterioration
      subsequent to their recent pathological experience (e.g. Trauma, falls, surgery),
      to a lack of knowledge about their medication or to reduced motivation. Patients
      who do not regain their independence not only represent increased health
      expenditure but also an increase in the risks connected with erroneous self
      medication.

PMID- 20059890
TI  - [Gerontological and geriatric education in baccalaureate nursing degree: a
      national survey].
AB  - Nowadays most nurses have to care for elderly people and in the future this will
      become always more frequent due to progressive ageing of population. Thus nurses
      will need to have the necessary skills so as to be able to answer to the many
      complex needs of this population. A national survey has been carried out to find
      out what kind of Gerontological education currently exists in Italian nursing
      degree courses. A questionnaire was sent out to all the coordinators/directors of
      the Nursing Schools in the 171 educational locations within the 38 Italian
      universities where the degree course was active during the academic year
      2005/2006. 34 university (84.4%) and 88 of the 171 locations (51.4%) answered the
      questionnaire.A certain variety is present at national level for theoretical and
      clinical education in Geriatrics and Gerontology, in terms, for example, of
      number of credits, type of clinical placements and time in the curricula for the
      educational experiences; most Nursing Schools have specific courses dedicated to
      Geriatric/Gerontological contents. Moreover coordinators/directors believe that
      the space offered to Geriatrics education is enough and that overloading of the
      curriculum would be a more considerable obstacle to the introduction and to the
      increase of Geriatric content in the curricula. Although not all Italian Nursing
      Schools participated, this survey provides relevant information about present
      education offered in elderly care in Italy, and permits us to give useful
      suggestions to Italian educators and nursing tutors.

PMID- 20059891
TI  - [Building a quality evaluation system for the nursing triage process].
AB  - In literature there are no studies regarding the quality evaluation of the whole
      triage process; however, since it is necessary to evaluate what really happens
      everyday in the Emergency Rooms, as well as verifying the daily level of
      throughput, there is a strong need for an appropriate tool. Measuring the quality
      of triage means improving the caring process. This article presents a new
      measurement grid, aimed at realizing a Quality Evaluation of Nursing Care.
      Currently, the most widespread systems used for the QENC are the Australian
      Triage Scale, the Canadian triage and Acuity Scale and the Italian Group of
      Triage Scale. The global/biphasic triage system was used in our study because it
      seems the most accurate, according to literature. There are several indicators
      that evaluate many aspects of the triage process; every single indicator has a
      score. The sum of the scores defines the quality level of the nursing triage
      process. Our paper discusses the application of this score in a major Milan
      hospital, based upon a preliminary study.

PMID- 20059892
TI  - [Application of the balanced scorecard for evaluating the training process].
AB  - A training project in which nurses acted as tutors to novice nurses was
      introduced in the Ferrara University Hospital, with the aim of helping them to
      achieve the skills and professional expertise required in an operating theatre
      environment. Owing to the involvement of all the surgical divisions of the
      hospital and the continual addition of new staff, the Balanced Scorecard method
      (BSC) was used to assess the impact of training on the entire organization. The
      BSC method, a multidimensional method born in the USA in the 1990's, made it
      possible to assess the utility of training in the light of achieving
      institutional goals.

PMID- 20059893
TI  - [Quality of life and social support for women with breast cancer: research
      study].
AB  - The expression "quality of life" was used for the first time by Pigou in 1920 in
      a textbook on economy and welfare , but was only regarded seriously in social
      terms in the 1960's before becoming a medical issue. Although it is difficult to
      define, the WHO has stated that "the quality of life is how an individual
      perceives his own life, in the light of the cultural context and values of
      his/her environment ,and his/her aims, expectations and worries. According to the
      Outcome Research the quality of life becomes a mere quantification of some health
      aspects described ty the patient using standardized tools. The theoretical model
      adopted was the concept of social support as a determining element in improving
      the quality of life, devised by J.E Ware , that emphasizes how the quality of
      life in oncological patients is positively influenced by strong social support.
      The aim of the study is to evaluate the existence of a positive relationship
      between the perception of family support and the quality of life in young women
      who have survived breast cancer.

PMID- 20059894
TI  - [EU-Project "healthPROelderly" - evidence-based guidelines on health promotion
      for older people: social determinants, inequality and sustainability].
AB  - In this phase of rapid demographic change and low birth rate , coupled with an
      increasing life expectancy , the challenge for the future consists of being able
      to age in good health . European policies should therefore be aimed at promoting
      healthiness in the elderly and, although some CEE countries have introduced
      various projects and schemes, the majority are of a national or local nature and
      do not take into account the European context. The healthPROelderly project, on
      the other hand , is aimed at collecting information in the countries who
      participate in the project to pinpoint the best schemes for promoting healthiness
      in the elderly. This study focuses on the models that have a sustainable approach
      as far as socio-economical, environmental and lifestyle aspects are concerned.
      The specific aim of the project is to identify the criteria that have the highest
      impact on health schemes for the elderly and to establish relative guidelines at
      local, national and European level.

PMID- 20059895
TI  - [The waiting process in relatives of patients submitted to surgery: staff
      perceptions].
AB  - Waiting for a close relative undergoing health treatment is an issue mainly
      considered in the light of intensive care structures whereas litte attention had
      been paid to the waiting process during surgery, particularly with reference to
      health workers. The aim of this study was to describe how health workers
      perceived this process and how they behaved, in a small hospital in North-Eastern
      Italy, by means of a semi-structured interview. The problems and needs perceived
      by the 41 health workers were mainly psychological: anxiety and stress due to
      waiting ,lack of information about the operation and post-operative conditions.
      Results showed that no specific action was taken regarding relatives: information
      was provided on an individual basis and almost always once the operation had
      ended. Nurses sustained that this information should be provided by physicians.
      These results are similar to those published in the literature. Health workers
      were however aware of the need to provide relatives with adequate support during
      operations.

PMID- 20059896
TI  - [The perception of the risk related to nursing activities in Bachelor student of
      Modena and Reggio Emilia university: An observational study].
AB  - Professional risk and security in the health sector is becoming ever more
      important : the number of accidents in hospital environments during 2005 was
      19,000 and nurses were the most frequently involved category. This study deals
      with clinical risk perception . A questionnaire was issued to 259 student and 100
      professional nurses at the Modena and Reggio Emilia University Hospital.,
      comprising 70 questions regarding 5 dimensions: general risk perception, personal
      risk perception, nursing skills, observed experience and direct experience.
      Results were evaluated using the ANOVA and t-tests and showed significant
      differences among the various groups (first, second and third-year students and
      professional nurses) in relation to each dimension. On the whole , the perception
      of risk was relatively low in comparison to its real level in the working
      environment. Therefore, specific training for a correct perception of health
      risks is required, not only for students but also for trained nurses, so that the
      culture of risk management becomes a routine issue.

PMID- 20059897
TI  - Genotypic identification of some lactic acid bacteria by amplified fragment
      length polymorphism analysis and investigation of their potential usage as
      starter culture combinations in Beyaz cheese manufacture.
AB  - In this study, 2 different starter culture combinations were prepared for
      cheesemaking. Starter culture combinations were formed from 8 strains of lactic
      acid bacteria. They were identified as Lactococcus lactis ssp. lactis (2
      strains), Lactobacillus plantarum (5 strains), and Lactobacillus paraplantarum (1
      strain) by amplified fragment length polymorphism analysis. The effects of these
      combinations on the physicochemical and microbiological properties of Beyaz
      cheeses were investigated. These cheeses were compared with Beyaz cheeses that
      were produced with a commercial starter culture containing Lc. lactis ssp. lactis
      and Lc. lactis ssp. cremoris as control. All cheeses were ripened in brine at 4
      degrees C for 90 d. Dry matter, fat in dry matter, titratable acidity, pH, salt
      in dry matter, total N, water-soluble N, and ripening index were determined.
      Sodium dodecyl sulfate-PAGE patterns of cheeses showed that alpha(S)-casein and
      beta-casein degraded slightly during the ripening period. Lactic acid bacteria,
      total mesophilic aerobic bacteria, yeast, molds, and coliforms were also counted.
      All analyses were repeated twice during d 7, 30, 60, and 90. The starter culture
      combinations were found to be significantly different from the control group in
      pH, salt content, and lactobacilli, lactococci, and total mesophilic aerobic
      bacteria counts, whereas the cheeses were similar in fat, dry matter content, and
      coliform, yeast, and mold counts. The sensory analysis of cheeses indicated that
      textural properties of control cheeses presented somewhat lower scores than those
      of the test groups. The panelists preferred the tastes of treatment cheeses,
      whereas cheeses with starter culture combinations and control cheeses had similar
      scores for appearance and flavor. These results indicated that both starter
      culture combinations are suitable for Beyaz cheese production.

PMID- 20059898
TI  - Casein micelle dissociation in skim milk during high-pressure treatment: effects
      of pressure, pH, and temperature.
AB  - The effect of pH (from 5.5 to 7.5) and temperature (from 5 to 40 degrees C) on
      the turbidity of reconstituted skim milk powder was investigated at ambient
      pressure and in situ under pressure (up to 500MPa) by measurement of light
      scattering. High-pressure treatment reduced the turbidity of milk for all
      combinations of pH and temperature due to micelle dissociation. The turbidity
      profiles had a characteristic sigmoidal shape in which almost no effect on
      turbidity was observed at low pressures (100MPa), followed by a stronger pressure
      dependency over a pressure range of 150MPa during which turbidity decreased
      extremely. From the turbidity profiles, the threshold pressure for disruption of
      micelle integrity was determined and ranged from 150MPa at low pH to 350-400MPa
      at high pH. The threshold pressure diagram clearly showed a relationship between
      the barostability of casein micelles and pH, whereas almost no effect of
      temperature was shown. This remarkable pH effect was a consequence of pressure
      induced changes in the electrostatic interactions between colloidal calcium
      phosphate and the caseins responsible for maintaining micellar structure and was
      explained by a shift in the calcium phosphate balance in the micelle-serum
      system. Accordingly, a mechanism for high pressure-induced disruption of micelle
      integrity is suggested in which the state of calcium plays a crucial role in the
      micelle dissociation process.

PMID- 20059899
TI  - Neutral glycosphingolipid content of ovine milk.
AB  - Milk glycosphingolipids (GSL) have been reported to participate in the newborn's
      defense against pathogens. Taking this into account, in this study we determined
      the neutral GSL content of ovine milk, including its fatty acid profile. Its role
      in bacterial adhesion was also addressed by immunodetection of separate GSL in a
      high-performance thin-layer chromatography overlay assay. Ovine milk has a
      neutral GSL pattern similar to human milk and includes lactosylceramide (LacCer;
      45.7%), monohexosylceramide (glucosylceramide and galactosylceramide, 31.2%),
      globotriaosylceramide (Gb3; 19.1%), and globotetraosylceramide (Gb4; 3.5%).
      Globotriaosylceramide and Gb4 are present in human but not bovine milk. Neutral
      GSL contained C23:0 and C24:0 as the most abundant fatty acids, a finding
      consistent with its high content of very long chain fatty acids (longer than
      C20). Most fatty acids were saturated and had a low content of polyunsaturated
      fatty acids. Bovine enterotoxigenic Escherichia coli strains bound strongly to
      LacCer and showed a weak binding to monohexosylceramide. The K99 strain also
      bound strongly to Gb3, and F41 to Gb4. Lactosylceramide, monohexosylceramide, and
      Gb3 were also observed to bind to human uropathogenic E. coli strains. The
      results reported here show the ability of neutral GSL in ovine milk to bind to E.
      coli strains. These compounds could be used as an alternative and available
      source to supplement infant or bovine formulas with a view to preventing
      bacterial infections.

PMID- 20059900
TI  - Short communication: effect of kefir grains on proteolysis of major milk
      proteins.
AB  - The effect of kefir grains on the proteolysis of major milk proteins in milk
      kefir and in a culture of kefir grains in pasteurized cheese whey was followed by
      reverse phase-HPLC analysis. The reduction of kappa-, alpha-, and beta-caseins
      (CN), alpha-lactalbumin (alpha-LA), and beta-lactoglobulin (beta-LG) contents
      during 48 and 90 h of incubation of pasteurized milk (100mL) and respective
      cheese whey with kefir grains (6 and 12 g) at 20 degrees C was monitored.
      Significant proteolysis of alpha-LA and kappa-, alpha-, and beta-caseins was
      observed. The effect of kefir amount (6 and 12 g/100mL) was significant for alpha
      LA and alpha- and beta-CN. alpha-Lactalbumin and beta-CN were more easily
      hydrolyzed than alpha-CN. No significant reduction was observed with respect to
      beta-LG concentration for 6 and 12 g of kefir in 100mL of milk over 48 h,
      indicating that no significant proteolysis was carried out. Similar results were
      observed when the experiment was conducted over 90 h. Regarding the cheese whey
      kefir samples, similar behavior was observed for the proteolysis of alpha-LA and
      beta-LG: alpha-LA was hydrolyzed between 60 and 90% after 12h (for 6 and 12 g of
      kefir) and no significant beta-LG proteolysis occurred. The proteolytic activity
      of lactic acid bacteria and yeasts in kefir community was evaluated. Kefir milk
      prepared under normal conditions contained peptides from proteolysis of alpha-LA
      and kappa-, alpha-, and beta-caseins. Hydrolysis is dependent on the kefir:milk
      ratio and incubation time. beta-Lactoglobulin is not hydrolyzed even when higher
      hydrolysis time is used. Kefir grains are not appropriate as adjunct cultures to
      increase beta-LG digestibility in whey-based or whey-containing foods.

PMID- 20059901
TI  - Hot topic: Enhancing omega-3 fatty acids in milk fat of dairy cows by using
      stearidonic acid-enriched soybean oil from genetically modified soybeans.
AB  - Very long chain n-3 fatty acids such as eicosapentaenoic acid (EPA; 20:5n-3) are
      important in human cardiac health and the prevention of chronic diseases, but
      food sources are limited. Stearidonic acid (SDA; 18:4n-3) is an n-3 fatty acid
      that humans are able to convert to EPA. In utilizing SDA-enhanced soybean oil
      (SBO) derived from genetically modified soybeans, our objectives were to examine
      the potential to increase the n-3 fatty acid content of milk fat and to determine
      the efficiency of SDA uptake from the digestive tract and transfer to milk fat.
      Three multiparous, rumen-fistulated Holstein cows were assigned randomly in a 3 x
      3 Latin square design to the following treatments: 1) control (no oil infusion);
      2) abomasal infusion of SDA-enhanced SBO (SDA-abo); and 3) ruminal infusion of
      SDA-enhanced SBO (SDA-rum). The SDA-enhanced SBO contained 27.1% SDA, 10.4% alpha
      linolenic acid, and 7.2% gamma-linolenic acid. Oil infusions provided 57 g/d of
      SDA with equal amounts of oil infused into either the rumen or abomasum at 6-h
      intervals over a 7-d infusion period. Cow numbers were limited and no treatment
      differences were detected for DMI or milk production (22.9+/-0.5 kg/d and 32.3+/
      0.9 kg/d, respectively; least squares means +/- SE), milk protein percentage and
      yield (3.24+/-0.04% and 1.03+/-0.02 kg/d), or lactose percentage and yield
      (4.88+/-0.05% and 1.55+/-0.05 kg/d). Treatment also had no effect on milk fat
      yield (1.36+/-0.03 kg/d), but milk fat percentage was lower for the SDA-rum
      treatment (4.04+/-0.04% vs. 4.30+/-0.04% for control and 4.41+/-0.05% for SDA
      abo). The SDA-abo treatment increased n-3 fatty acids to 3.9% of total milk fatty
      acids, a value more than 5-fold greater than that for the control. Expressed as a
      percentage of total milk fatty acids, values (least squares means +/- SE) for the
      SDA-abo treatment were 1.55+/-0.03% for alpha-linolenic acid (18:3n-3), 1.86+/
      0.02 for SDA, 0.23 +/- <0.01 for eicosatetraenoic acid (20:4n-3), and 0.18+/-0.01
      for EPA. Transfer efficiency of SDA to milk fat represented 39.3% (range=36.8 to
      41.9%) of the abomasally infused SDA and 47.3% (range=45.0 to 49.6%) when the n-3
      fatty acids downstream from SDA were included. In contrast, transfer of ruminally
      infused SDA to milk fat averaged only 1.7% (range=1.3 to 2.1%), indicating
      extensive rumen biohydrogenation. Overall, results demonstrate the potential to
      use SDA-enhanced SBO from genetically modified soybeans combined with proper
      ruminal protection to achieve impressive increases in the milk fat content of SDA
      and other n-3 fatty acids that are beneficial for human health.

PMID- 20059902
TI  - Variability of mammary blood flow in lactating Holstein-Friesian cows during the
      first twelve weeks of lactation.
AB  - The goals of the present study were to measure mammary blood flow volume (BFV)
      during the first 12 wk of lactation in dairy cows by using color Doppler
      sonography and to determine what affects the mammary blood flow. Forty cows were
      examined via color Doppler sonography on d 1, 7, 14, 28, 56, and 84 after
      parturition (d 0). The total BFV (BFV(total)) to the 4 mammary glands was
      calculated by measuring time-averaged maximum velocities (TAMV) and cross
      sectional areas (A) of the left and right pudendoepigastric trunks via
      transrectal color Doppler sonography. Because there were no significant
      differences in A, TAMV, and BFV between the right and left pudendoepigastric
      trunks, the means of A and TAMV, and the BFV(total) of both trunks were used for
      calculations. The intraindividual and interindividual variability of repeated BFV
      measures quantified by intraclass correlation coefficients were 96 and 98%,
      respectively. The BFV(total) ranged from 19.9 to 27.9 L/min, with a mean of
      22.3+/-4.9 L/min. Interindividual differences in BFV values were attributable to
      variations in A and TAMV. The interindividual variability of the BFV(total),
      which was determined using the coefficients of variation of the BFV(total) on
      individual days, ranged from 16 to 28%. All the cows had similar changes in the
      BFV(total) during the study. Changes in BFV(total) were not correlated with
      changes in the mean of A, but there was a good correlation between changes in
      BFV(total) and in the mean of TAMV (r=0.94). The BFV(total) was highest on d 1 of
      lactation, decreased 28% by d 7, and remained at this level until d 28. By d 56,
      the BFV(total) had increased by 15% compared with d 14 and by 10% compared with d
      28. The BFV(total) on d 84 was significantly different from all other days except
      d 56. There were moderate correlations between daily milk yield and BFV on
      individual days (0.24<r<0.35). In conclusion, Doppler sonography is a reliable
      method for determining blood flow in the pudendoepigastric trunk of cows. There
      is great variability in mammary blood flow among cows and in BFV.

PMID- 20059903
TI  - Pressure distribution at the teat-liner and teat-calf interfaces.
AB  - During milking, the teat is loaded because of a combination of vacuum and
      pressure of the collapsing liner. It is assumed that pressure concentrations tend
      to cause teat-end injuries and hyperkeratosis. The pressure distribution on the
      bovine teat was measured to test the hypothesis that the pressures of the
      collapsed liner are unevenly distributed over the teat. With the aid of a
      pressure-sensitive sensor (approximately 2 gauge points/cm(2)), the pressures at
      the teat-liner and the teat-calf interfaces were measured at 100 Hz. Pressure
      distribution over the surface of an artificial teat was measured with 7 different
      liners, 1 liner at 3 different vacuum levels, and a suckling calf. One cow was
      equipped with a sensor at a teat during a milking with one of the liners.
      Conventional round liners concentrated the load over 2 sites at the teat end.
      Some liners (softer material, reduced tension, smaller barrel, reduced mouthpiece
      depth) distributed the compressive load over a larger area of the teat. Although
      all liners distributed the highest pressures at the teat end, some liner designs
      showed a 25% reduction at the site of interest at vacuum of 44 kPa. The calf
      forced milk flow by a combination of suckling and overpressure in the teat
      cistern caused by the tongue. While the calf was swallowing, teat pressure was
      reduced because of a decrease in vacuum. Moreover, the calf did not load the teat
      end, probably because the teat canal would be closed and the milk would not flow.
      The method of using a pressure sensor to analyze teat loading at the teat-liner
      and the teat-calf interfaces showed potential and is a first step toward
      developing a natural milking technique.

PMID- 20059904
TI  - Biomechanics and histology of bovine claw suspensory tissue in early acute
      laminitis.
AB  - Weakening of the suspensory tissue supporting the pedal bone is the central issue
      in the theory of acute bovine laminitis, but this aspect has never been tested.
      The objective of this study was to investigate the effect of laminitis on the
      suspensory tissue. The hypothesis was that clinical and histological signs of
      acute laminitis are associated with decreased strength of the suspensory tissue
      of the bovine claw. Nonpregnant dairy heifers (n=10) received oral oligofructose
      overload (17 g/kg of body weight) and were killed 24 (n=4) and 72h (n=6) after
      overload. Control heifers (n=6) received tap water and were killed at 72 or 96h.
      Clinical, orthopedic, and histological examinations were carried out to confirm
      the occurrence of laminitis. After euthanasia, 2 adjacent tissue samples
      including the horn wall, lamellar layer, dermis, and pedal bone were cut from the
      dorso-abaxial aspect of each claw. Tissue samples were kept on ice until mounted
      on a mechanical testing frame, fixed by horn and bone, and loaded to failure. A
      stress displacement curve was generated and measurements of physiological support
      (force needed to displace 1mm beyond first resistance) and maximal support (force
      needed to break the tissue) were recorded. Heifers treated with oligofructose
      developed clinical signs consistent with ruminal and systemic acidosis after
      treatment as well as acute laminitis, characterized by weight shifting (35% of
      observations vs. 6% in controls), moderate lameness (100 vs. 17%, score of 3 out
      of 5 at 72h), and reaction to hoof testing (30 and 50% at 48 and 72h,
      respectively, vs. 0% in controls). Histological examination of claws from heifers
      killed 72h after overload showed changes consistent with acute laminitis,
      including stretched lamellae, wider basal cells with low chromatin density, and a
      thick, wavy, and blurry appearance of the basement membrane. Biomechanical
      results showed no effect of oligofructose overload on physiological support of
      the suspensory tissue at 24 and 72h after overload; in contrast, overload
      increased maximal support of the tissue 72h after overload. Herd of origin and
      location of the sample had large effects on both physiological support and
      maximal support (herd=547 N/cm(2); location=531 N/cm(2)) of claw suspensory
      tissue (herd=260 N/cm(2); location=327 N/cm(2)). Despite clinical and
      histological signs of laminitis, no weakening of the suspensory tissue of the
      bovine claw was detected at 24 and 72h after oligofructose overload. Herd factors
      appeared to be important for claw suspensory tissue strength.

PMID- 20059905
TI  - Suitability of low-dosage oxytocin treatment to induce milk ejection in dairy
      cows.
AB  - Chronic use of high oxytocin (OT) dosages can cause a reduced response to
      endogenous OT. In this study the OT dosages used in the milking practice of 82
      dairy cow farms were recorded. The OT dosages per cow used were high, especially
      when injected i.m. (23+/-2 IU) compared with i.v. (7+/-1 IU). In addition, the
      minimum OT dosages needed to obtain normal milk removal in cows with disturbed
      milk ejection were investigated. Seventeen cows routinely treated with OT during
      milking (group T) and 17 cows without previous OT treatment were used (group C).
      After cessation of spontaneous milk flow, both T and C groups were injected i.v.
      with a low dosage of OT (0.2 or 0.5 IU/cow). The time from injection until
      cessation of the OT-induced milk flow was recorded (response phase). The response
      phase and the amounts of removed milk by effect of the OT injection increased
      with increasing OT dosage. Values for 0.2 and 0.5 IU/cow of OT injected i.v. were
      (response phase and amount of milk removed) 198+/-27 and 302+/-18s and 3.4+/-0.7
      kg and 6.5+/-1.3 kg, respectively, for the C group, and 157+/-15 and 221+/-16s
      and 3.2+/-0.5 and 5.5+/-1.0 kg, respectively, for the T group. Within 20 min of
      the OT injection, plasma concentrations returned to basal levels. The threshold
      OT concentration at cessation of milk flow after injection of 0.2 or 0.5 IU/cow
      of OT was calculated based on the OT plasma half-life. The threshold increased
      with increasing dosages of OT and was higher in group T (8+/-1 and 14+/-1 pg/mL
      for 0.2 and 0.5 IU/cow, respectively) than in group C (7+/-1 and 11+/-1 pg/mL for
      0.2 and 0.5 IU/cow, respectively). In conclusion, desensitization of the udder
      toward OT occurs when the udder is exposed to elevated OT plasma concentrations,
      both short-term during the actual milking and long-term due to chronic high
      dosage OT treatment. However, low-dosage OT treatments to induce normal milk
      removal can minimize the observed side effects.

PMID- 20059906
TI  - Preferences of dairy cows for three stall surface materials with small amounts of
      bedding.
AB  - Farmers' concerns about the economy, cost of labor, and hygiene have resulted in
      reduced use of organic bedding in stalls for dairy cows; however, the reduced use
      of organic bedding possibly impairs cow comfort. The effects of different stall
      surface materials were evaluated in an unheated building in which only a small
      amount of bedding was used. The lying time and preferences of 18 cows using 3
      stall surface materials (concrete, soft rubber mat, and sand) were compared. All
      materials were lightly bedded with a small amount of straw, and the amount of
      straw added to each stall was measured. The cows only had access to stalls of one
      surface type while their lying time was observed. Lying times were longest on the
      rubber mats compared with other surfaces (rubber mat 768; concrete 727; sand
      707+/-16 min/d). In a preference test, cows had access to 2 of the 3 types of
      stalls for 10 d and their stall preference was measured. Cows preferred stalls
      with rubber mats to stalls with a concrete floor (median 73 vs. 18 from a total
      of 160 observations per day; interquartile range was 27 and 12, respectively),
      but showed no preference for sand stalls compared with stalls with a concrete
      floor or with rubber mats. More straw was needed on sand stalls compared with
      concrete or mat (638+/-13 g/d on sand, 468+/-10 g/d on concrete, and 464+/-8 g/d
      on rubber mats). Lying times on bedded mats indicated that mats were comfortable
      for the cows. If availability or cost of bedding material requires limiting the
      amount of bedding used, rubber mats may help maintain cow comfort.

PMID- 20059907
TI  - Optimal replacement policies for dairy cows based on daily yield measurements.
AB  - Markov decision processes (MDP) with finite state and action space have often
      been used to model sequential decision making over time in dairy herds. However,
      the length of each stage has been at least 1 mo, resulting in models that do not
      support decisions on a daily basis. The present paper describes the first step of
      developing an MDP model that can be integrated into a modern herd management
      system. A hierarchical MDP was formulated for the dairy cow replacement problem
      with stage lengths of 1 d. It can be used to assist the farmer in replacement
      decisions on a daily basis and is based on daily milk yield measurements that are
      available in modern milking systems. Bayesian updating was used to predict the
      performance of each cow in the herd and economic decisions were based on the
      prediction. Moreover, parameters in the model were estimated using data records
      of the specific herd under consideration. This includes herd-specific lactation
      curves.

PMID- 20059908
TI  - Susceptibility of Escherichia coli isolated from uteri of postpartum dairy cows
      to antibiotic and environmental bacteriophages. Part I: Isolation and lytic
      activity estimation of bacteriophages.
AB  - The objective of this study was to isolate bacteriophages from environmental
      samples of 2 large commercial dairy farms using Escherichia coli isolated from
      the uteri of postpartum Holstein dairy cows as hosts. A total of 11 bacteriophage
      preparations were isolated from manure systems of commercial dairy farms and
      characterized for in vitro antimicrobial activity. In addition, a total of 57 E.
      coli uterine isolates from 5 dairy cows were phylogenetically grouped by triplex
      PCR. Each E. coli bacterial host from the uterus was inoculated with their
      respective bacteriophage preparation at several different multiplicities of
      infections (MOI) to determine minimum inhibitory MOI. The effect of a single dose
      (MOI=10(2)) of bacteriophage on the growth curve of all 57 E. coli isolates was
      assessed using a microplate technique. Furthermore, genetic diversity within and
      between the different bacteriophage preparations was assessed by bacteriophage
      purification followed by DNA extraction, restriction, and agarose gel
      electrophoresis. Phylogenetic grouping based on triplex PCR showed that all
      isolates of E. coli belonged to phylogroup B1. Bacterial growth was completely
      inhibited at considerably low MOI, and the effect of a single dose (MOI=10(2)) of
      bacteriophage preparations on the growth curve of all 57 E. coli isolates showed
      that all bacteriophage preparations significantly decreased the growth rate of
      the isolates. Bacteriophage preparation 1230-10 had the greatest antimicrobial
      activity and completely inhibited the growth of 71.7% (n=57) of the isolates. The
      combined action of bacteriophage preparations 1230-10, 6375-10, 2540-4, and 6547
      2, each at MOI=10(2), had the broadest spectrum of action and completely
      inhibited the growth (final optical density at 600 nm <or=0.1) of 80% of the E.
      coli isolates and considerably inhibited the growth (final optical density at 600
      nm <or=0.2) of 90% of the E. coli isolates. Restriction profile analysis
      demonstrated that all 4 phage preparations contained bacteriophages that were
      genetically distinct from each other according to the banding pattern of the
      fragments. The combination of several different bacteriophages can improve the
      spectrum of action, and the results of this study suggest that bacteriophages
      1230-10, 6375-10, 2540-4, and 6547-2 should be used in combination as a cocktail.

PMID- 20059909
TI  - Susceptibility of Escherichia coli isolated from uteri of postpartum dairy cows
      to antibiotic and environmental bacteriophages. Part II: In vitro antimicrobial
      activity evaluation of a bacteriophage cocktail and several antibiotics.
AB  - The use of pathogenic-specific antimicrobials, as proposed by bacteriophage
      therapy, is expected to reduce the incidence of resistance development. Eighty
      Escherichia coli isolated from uteri of Holstein dairy cows were phenotypically
      characterized for antimicrobial resistance to ampicillin, ceftiofur,
      chloramphenicol, florfenicol, spectinomycin, streptomycin, and tetracycline by
      broth microdilution method. The lytic activity of a bacteriophage cocktail
      against all isolates was performed by a similar method. Additionally, the effect
      of different concentrations of antimicrobials and multiplicities of infections
      (MOI) of the bacteriophage cocktail on E. coli growth curve was measured.
      Isolates exhibited resistance to ampicillin (33.7%), ceftiofur (1.2%),
      chloramphenicol (100%), and florfenicol (100%). All strains were resistant to at
      least 2 of the antimicrobial agents tested; multidrug resistance (>or=3 of 7
      antimicrobials tested) was observed in 35% of E. coli isolates. The major
      multidrug resistance profile was found for ampicillin-chloramphenicol
      florfenicol, which was observed in more than 96.4% of the multidrug-resistant
      isolates. The bacteriophage cocktail preparation showed strong antimicrobial
      activity against multidrug-resistant E. coli. Multiplicity of infection as low as
      10(-4) affected the growth of the E. coli isolates. The ratio of 10 bacteriophage
      particles per bacterial cell (MOI=10(1)) was efficient in inhibiting at least 50%
      of all isolates. Higher MOI should be tested in future in vitro studies to
      establish ratios that completely inhibit bacterial growth during longer periods.
      All isolates resistant to florfenicol were resistant to chloramphenicol and,
      because florfenicol was recently introduced into veterinary clinics, this finding
      suggests that the selection pressure of chloramphenicol, as well as other
      antimicrobials, may still play a relevant role in the emergence and dissemination
      of florfenicol resistance in E. coli. The bacteriophage cocktail had a notable
      capacity to inhibit the in vitro growth of E. coli isolates, and it may be an
      attractive alternative to conventional treatment of metritis by reducing E. coli
      in uteri of postpartum dairy cows.

PMID- 20059910
TI  - Costs and efficacy of management measures to improve udder health on Dutch dairy
      farms.
AB  - Many different management measures are available to control mastitis, a very
      costly disease in the dairy sector. The objective of this paper was to evaluate
      the costs and efficacies of 18 of these management measures, for contagious and
      environmental pathogens, and their effect on bulk tank somatic cell count (BTSCC)
      and incidence of clinical mastitis (CM). To determine the efficacies for these
      management measures, literature data and expertise were combined using Monte
      Carlo expert evaluation analysis. The effect of management measures varied with
      the incidence of CM and BTSCC, as well as for environmental and contagious
      problems. On average, postmilking teat disinfection was found to be the most
      effective measure in all situations. All management measures had large
      uncertainty around the most likely value. Results of a data envelopment analysis
      showed that 4 of the management measures included formed the best-practice
      frontier (the most cost-efficient measures): keeping cows standing after milking,
      rinsing clusters after milking a clinical case, using a separate cloth for all
      cows, and wearing milkers' gloves. Of the top 25 management measures (the 18 base
      management measures including levels of compliance), 8 were measures with 100%
      compliance; the others were sublevels of these measures with compliance varying
      between 25 and 100%. A lower hourly rate of the farmer did not influence
      management measures from the best-practice frontier, but had some effect on the
      efficiency scores of the other management measures.

PMID- 20059911
TI  - The amount of shade influences the behavior and physiology of dairy cattle.
AB  - The objective was to understand how the amount of shade (shade cloth blocking 99%
      of solar radiation) influenced the behavior and physiology of Holstein-Friesian
      dairy cattle managed on pasture. We compared behavior, body temperature, and
      respiration rate of cattle provided with 1 of 3 treatments for 5 d: access to
      2.4m(2) or 9.6m(2) shade/cow, or no shade (n=4 groups/treatment, 10
      animals/group). Behavioral observations were carried out between 1000 and 1550h.
      Cows spent more than twice as much time in the larger shade (24 vs. 50% of
      observations for 2.4m(2) and 9.6m(2) shade/cow, respectively, SED: 1.7%) and
      engaged in fewer aggressive interactions when more shade was provided (10.7 vs.
      3.2 aggressive interactions/m(2) during 5.8h of observation for 2.4m(2) and
      9.6m(2) shade/cow, respectively, SED: 3.16 interactions/m(2)). Time around the
      water trough increased when little or no shade was provided (11, 5, and 2% of
      observations within 4.5m of water trough for no shade, 2.4m(2), and 9.6m(2)
      shade/cow, SED: 2.4%). Respiration rate was higher when cows had less shade
      available (62, 57, and 51 breaths/min for no shade, 2.4m(2), and 9.6m(2)
      shade/cow, respectively, SED: 2.1 breaths/min). All cows used the shade more when
      9.6m(2) shade/cow was provided; simultaneous use was observed in 15 versus 0% of
      observations in the 9.6m(2) and 2.4m(2) treatments on the warmest day,
      respectively. Weather conditions influenced both the behavioral and physiological
      responses, and these changes were more pronounced when less or no shade was
      available. Cows spent more time in shade and less time lying with increasing heat
      load. In addition, aggressive interactions in the shade, time around the water
      trough, mean body temperature, and respiration rate increased with environmental
      heat load. Our findings highlight the importance of determining and providing an
      effective amount of shade to cattle.

PMID- 20059912
TI  - Microbiological quality of raw milk used for small-scale artisan cheese
      production in Vermont: effect of farm characteristics and practices.
AB  - This study 1) evaluated the overall milk quality and prevalence of 4 target
      pathogens (Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., and
      Escherichia coli O157:H7) in raw milk used for small-scale artisan cheesemaking
      and 2) examined specific farm characteristics and practices and their effect on
      bacterial and somatic cell counts (SCC). Raw milk samples were collected weekly
      from 21 artisan cheese operations (6 organic) in the state of Vermont that
      manufactured raw-milk cheese from cow (12), goat (5), or sheep (4) milk during
      the summer of 2008. Individual samples were examined for standard plate counts
      (SPC), coliform counts (CC), and SCC. Samples were also screened for target
      pathogens both quantitatively and qualitatively by direct plating and PCR.
      Overall, 86% of samples had SPC <10,000 cfu/mL, with 42% <1,000 cfu/mL.
      Additionally, 68% of samples tested were within pasteurized milk standards for
      coliform bacteria under the United States' Grade A Pasteurized Milk Ordinance at
      <10 cfu/mL. Log(10) SPC and CC did not differ significantly among species.
      Similarly, method of sample delivery (shipped or picked up), farm type (organic
      or conventional), and duration of milking (year-round or seasonal) did not have
      significant effects on farm aggregated mean log(10) SPC, CC, or SCC. Strong
      positive correlations were observed between herd size and mean log(10) SPC and
      between log(10) SPC and CC as well as SCC when data from all animal species were
      combined. Although SCC for cow milk were significantly lower than those for goat
      and sheep milk, 98, 71, and 92% of cow, sheep, and goat milk samples,
      respectively, were within the compliance limits of the United States' Grade A
      Pasteurized Milk Ordinance for SCC. Fourteen of the 21 farms (67%) were positive
      for Staph. aureus, detected in 38% of samples at an average level of 20 cfu/mL.
      Neither L. monocytogenes, E. coli O157:H7, or Salmonella spp. were detected or
      recovered from any of the 101 samples tested. Our results indicate that the
      majority of raw milk produced for small-scale artisan cheesemaking was of high
      microbiological quality with no detectable target pathogens despite the repeat
      sampling of farms. These data will help to inform risk assessments that evaluate
      the microbiological safety of artisan and farmstead cheeses, particularly those
      manufactured from raw milk.

PMID- 20059913
TI  - Duration of weaning, starter intake, and weight gain of dairy calves fed large
      amounts of milk.
AB  - When calves are weaned abruptly off large amounts of milk, weight gain is reduced
      as a result of low intake of starter. We compared gradual and abrupt weaning of
      40 calves allowed to drink up to 12kg of milk/d by automated feeders, housed in
      groups of 4, and weaned at 41 d abruptly or over 3 gradual weaning periods (4,
      10, or 22 d), with one calf within each group randomly allocated to each
      treatment, balancing for sex and birth weight. During the milk-feeding period,
      the calves weaned over 22 d drank the least milk and ate the most starter, but
      these calves had the lowest total digestible energy intake and weight gains. The
      abruptly weaned calves had the highest digestible energy intakes and weight gains
      during the period before weaning. During the 9 d following weaning, the calves
      weaned over 22 and 10 d ate more starter and had better weight gains than
      abruptly weaned calves and those weaned over 4 d. Abruptly weaned calves lost
      weight during this period. In summary, gradual weaning improved starter intake,
      but because of reduced milk availability, this resulted in reduced total
      digestible energy intake before weaning. Weaning over 10 d resulted in the best
      overall weight gains over the study.

PMID- 20059914
TI  - Nutrient availability and lactogenic hormones regulate mammary protein synthesis
      through the mammalian target of rapamycin signaling pathway.
AB  - The nutritional and endocrine factors affecting protein translation in the bovine
      mammary gland, and the molecular mechanisms mediating their effects, are not well
      understood. The objective of this study was to assess the role of the mammalian
      target of rapamycin (mTOR) signaling pathway in the regulation of mammary protein
      synthesis by nutrients and hormones. Mammary epithelial acini isolated from
      lactating dairy cows were treated in medium containing, alone or in combination,
      a mixture of AA or glucose and acetate (GA) as energy substrates, or a
      combination of the lactogenic hormones hydrocortisone, insulin, and prolactin
      (HIP). Changes in the rate of mammary protein synthesis and the phosphorylation
      state of components of the mTOR signaling pathway were measured. Mammary protein
      synthesis was 50% higher with increased availability of AA in medium. The
      presence of GA or treatment of mammary acini with HIP alone did not affect
      mammary protein synthesis. The stimulation of mammary protein synthesis by AA was
      enhanced by HIP treatment, but not by the presence of GA in medium. Treatment of
      mammary acini with HIP induced the phosphorylation of protein kinase B. This
      effect was augmented in the presence of either AA or GA in medium. The
      stimulation of mammary protein synthesis by AA and its enhancement by HIP were
      associated with increased phosphorylation of the mTOR substrates, p70 ribosomal
      protein S6 kinase-1, and eukaryotic initiation factor 4E (eIF4E)-binding protein
      1 (4E-BP1), and dissociation of 4E-BP1 from eIF4E. The results suggest that
      nutrients and hormones may modulate mammary protein synthesis through the mTOR
      signaling pathway.

PMID- 20059915
TI  - The frequency of unilateral milking alters leucine metabolism and amino acid
      removal by the mammary gland of lactating goats.
AB  - The objective of this study was to test whether mammary AA metabolism and blood
      flow (BF) fluctuate in relation to changes in milk protein yield brought about by
      unilateral milking frequency. To investigate these relationships, the vascular
      systems of the mammary glands of 4 lactating goats were separated by ligation and
      flow probes were fitted around the external pudic artery of each gland. Goats
      were subjected to 3 consecutive periods (5 d each) during which 1) both glands
      were milked twice daily (2x; period 1); 2) glands were unilaterally milked, with
      gland A milked 8 times daily and gland B milked incompletely (30% of period 1
      milk yield retained in the gland) once daily (8x vs. 1x; period 2); and 3) both
      glands milked twice daily (2x; period 3). On d 5 of periods 1 (2x) and 2 (8x vs.
      1x), arteriovenous [1-(13)C]Leu kinetics were monitored for each gland. Milk
      protein yield was greater for gland A compared with gland B. After 2x milking
      resumed in period 3, yields for both glands returned to period 1 levels.
      Similarly, BF increased (19%) for gland A (8x), whereas BF was decreased (21%)
      for gland B (1x). For both glands, BF returned to previous levels when 2x milking
      resumed in period 3. Mammary net uptakes and oxidation of Leu were greater for
      the gland milked 8x compared with that milked 1x. Net uptakes from blood of Ile,
      Leu, Val, Lys, Pro, and Arg were greater (39-79%) for the 8x compared with the 1x
      gland. In conclusion, the excess removal and oxidation by the mammary gland of
      some amino acids appears an obligatory requirement to support increases or
      decreases in milk protein yield when milking frequency is altered.

PMID- 20059916
TI  - Effects of heat stress and nutrition on lactating Holstein cows: II. Aspects of
      hepatic growth hormone responsiveness.
AB  - Heat stress (HS) is a multibillion-dollar problem for the global dairy industry,
      and reduced milk yield is the primary contributor to this annual economic loss.
      Feed intake declines precipitously during HS but accounts for only about 35% of
      the decreased milk synthesis, indicating that the physiological mechanisms
      responsible for decreased milk production during HS are only partly understood.
      Thus, our experimental objectives were to characterize the direct effects of HS
      on the somatotropic axis, a primary regulator of metabolism and milk yield. We
      recently reported no differences in mean growth hormone (GH) concentrations, GH
      pulsatility characteristics, or GH response to growth hormone releasing factor in
      HS versus pair-fed (PF) thermoneutral controls. Despite similarities in
      circulating GH characteristics, plasma insulin-like growth factor (IGF)-I
      concentrations were reduced during heat stress conditions but not in PF animals,
      suggesting that uncoupling of the hepatic GH-IGF axis may occur during HS. We
      investigated this possibility by measuring proximal indicators of hepatic GH
      signaling following a GH bolus. Heat stress but not PF decreased abundance of the
      GH receptor and GH-dependent signal transducer and activator of transcription
      (STAT)-5 phosphorylation. Consistent with reduced GH signaling through STAT-5,
      basal hepatic IGF-I mRNA abundance was lower in HS cows. Thus, the reduced
      hepatic GH responsiveness (in terms of IGF-I gene expression) observed during HS
      appears to involve mechanisms at least partially independent of reduced nutrient
      intake. The physiological significance of reduced hepatic GH receptor abundance
      during HS is unclear at this time. Aside from reducing IGF-I production, it may
      reduce other GH-sensitive bioenergetic processes such as gluconeogenesis.

PMID- 20059917
TI  - Identification of potential sources of Staphylococcus aureus in herds with
      mastitis problems.
AB  - Staphylococcus aureus is a common udder pathogen of dairy cows that often causes
      herd problems. Various mastitis control programs have been used to combat the
      problem but have not always been efficient in preventing new Staph. aureus
      infections, indicating the presence of possible sources of infection other than
      those traditionally considered. Therefore, the aim of the study was to identify
      potential sources of infection relevant for Staph. aureus mastitis within 5 dairy
      herds with udder health problems caused by Staph. aureus. Samples were collected
      from milk of lactating cows, from body sites, and from the environment of
      lactating cows, dry cows, late pregnant heifers, young heifers 4 to 12 mo old,
      and heifer calves 0 to 3 mo old. Isolates of Staph. aureus were identified and
      compared using pulsed-field gel electrophoresis. Four to 7 unique Staph. aureus
      pulsotypes were found within each herd, with one strain predominating in milk in
      each herd. The milk pulsotypes were also frequently isolated in body samples,
      especially on hock skin, and in the immediate environment of lactating cows, and
      were sometimes found in other animal groups, especially in dry cows and heifer
      calves 0 to 3 mo old. The prevalence of Staph. aureus in milk and other types of
      samples varied markedly between herds. Staphylococcus aureus isolates with
      genotypes indistinguishable from those found in milk also dominated in extra
      mammary sites within the dairy herds studied, and hock skin was identified as an
      important reservoir of Staph. aureus. The results contribute new knowledge
      necessary to improve strategies for udder health control in herds.

PMID- 20059918
TI  - Survival and replication of Mycoplasma species in recycled bedding sand and
      association with mastitis on dairy farms in Utah.
AB  - Mycoplasma spp., usually Mycoplasma bovis, are important bovine pathogens that
      can cause mastitis, metritis, pneumonia, and arthritis. The currently documented
      routes of transmission of Mycoplasma spp. are through contaminated milking
      equipment and by direct animal contact. The existence of environmental sources
      for Mycoplasma spp. and their role in transmission and clinical disease is poorly
      characterized. Mycoplasma spp. (confirmed as M. bovis in 2 of 4 samples tested
      using PCR) was found in recycled bedding sand originating from a dairy
      experiencing an outbreak of clinical mycoplasma mastitis. Mycoplasma spp. were
      subsequently found in bedding sand from 2 other dairies whose bulk-tank milk was
      mycoplasma-positive. The association between the occurrence of Mycoplasma spp. in
      recycled bedding sand and mycoplasma mastitis in cows was further investigated
      using a pile of recycled sand from dairy 1. Study objectives included the
      determination of factors associated with the concentration of Mycoplasma spp. in
      recycled bedding sand and the duration of survival of mycoplasmas in the sand. We
      also evaluated the efficacy of 2 disinfectants at 2 different concentrations each
      for the elimination of Mycoplasma spp. from contaminated sand. Mycoplasma spp.
      survived in the sand pile for 8 mo. The concentration of Mycoplasma spp. within
      the sand pile was directly related to temperature and precipitation. It was also
      positively associated with the growth of gram-negative microorganisms, suggesting
      the possibility of the formation of a biofilm. Ideal temperatures for replication
      of Mycoplasma spp. occurred between 15 and 20 degrees C. Moisture in the sand and
      movement of the sand pile also appeared to play a role in replication of
      mycoplasmas. We found that 0.5% sodium hypochlorite or 2% chlorhexidine were
      efficacious in eliminating Mycoplasma spp. from contaminated bedding sand.
      Recycled bedding sand could be an environmental source of Mycoplasma spp.,
      including M. bovis, infections in dairy cows. Future studies should investigate
      the contribution of this environmental source to the epidemiology of mycoplasma
      infections in dairy cattle.

PMID- 20059919
TI  - Continuous lactation effects on mammary remodeling during late gestation and
      lactation in dairy goats.
AB  - The present study aimed to 1) elucidate whether continuous milking during late
      gestation in dairy goats negatively affects mammary remodeling and hence milk
      production in the subsequent lactation, and 2) identify the regulatory factors
      responsible for changes in cell turnover and angiogenesis in the continuously
      lactating mammary gland. Nine multiparous dairy goats were used. One udder half
      was dried off approximately 9 wk prepartum (normal lactation; NL), and the other
      udder half of the same goat was milked continuously (continuous lactation; CL)
      until parturition or until the half-udder milk yields had dropped to below 50
      g/d. Mammary biopsies were obtained from each udder half just before the NL gland
      was dried off (before dry period), within the first 2 wk after drying-off (early
      dry period, samples available only for NL glands), in the mid dry period, within
      the last 2 wk before parturition (late dry period), and at d 1 (the day of
      parturition), 3, 10, 60, and 180 of lactation. Mammary morphology was
      characterized in biopsies by quantitative histology, and cell turnover was
      determined by immunohistochemistry (terminal deoxynucleotidyl transferase dUTP
      nick end labeling and Ki-67). Transcription of genes encoding factors involved in
      mammary epithelial cell (MEC) turnover and vascular function was quantified by
      quantitative reverse transcription PCR. Results demonstrated that omitting the
      dry period was possible in goats but was not as easy as claimed before. Renewal
      of MEC was suppressed in CL glands, which resulted in a smaller MEC population in
      the subsequent lactation. At the time of parturition (and throughout lactation),
      the mammary glands subjected to CL had smaller alveoli, more fully differentiated
      MEC, and a substantially larger capillary fraction compared with NL glands. The
      continuously lactating gland thus resembled a normally lactating gland in an
      advanced stage of lactation. None of the studied genomic factors could account
      for these treatment differences. The described characteristics in CL glands
      compared with NL glands indicated a gland maintained in lactation for a longer
      period.

PMID- 20059920
TI  - Therapeutic effects of antimicrobial treatment during lactation of recently
      acquired bovine subclinical mastitis: two linked randomized field trials.
AB  - Two linked randomized field trials were performed on 39 herds in the Netherlands
      to 1) determine therapeutic effects of antimicrobial treatment of recently
      acquired subclinical mastitis (RASCM) during lactation, 2) evaluate the effect of
      duration of subclinical mastitis on therapeutic outcome, and 3) identify factors
      related to the therapeutic success of RASCM. Cows with a first elevated composite
      somatic cell count (CSCC) after 2 consecutive low CSCC measurements were eligible
      for enrollment in trial 1 (treatment at the first elevated CSCC). Quarter milk
      samples were collected to determine bacteriological status for major pathogens
      and coagulase-negative staphylococci. Cows with one or more culture-positive
      quarters with a quarter somatic cell count (QSCC) >or=100,000 cells/mL were
      defined to have RASCM and were randomly assigned treatment or control (no
      treatment). Untreated cows from trial 1 that had a second elevated CSCC at the
      next milk recording were eligible for enrollment in trial 2 (treatment at the
      second elevated CSCC). In trial 2, staphylococci-positive cows (Staphylococcus
      aureus and coagulase-negative staphylococci) were randomly assigned to treatment
      or control. Farmers used their own treatment protocols to treat quarters in both
      trials. Bacteriological cure was defined as absence of the pathogen identified
      pre-intervention in 2 samples post-intervention; QSCC, CSCC, and milk yield were
      also analyzed. Hierarchical logistic and linear models were used to determine
      therapeutic effects and to identify factors related to therapy outcome. Treated
      quarters had a higher bacteriological cure rate than control quarters for all
      pathogens in both trials. Treatment resulted in lower QSCC and CSCC, whereas milk
      yield was not affected by treatment. Bacteriological cure of RASCM was better in
      quarters with a low QSCC pre-intervention and in coagulase-negative staphylococci
      positive quarters. Control quarters with a single culture-positive sample pre
      intervention also had a higher bacteriological cure than control quarters with
      >or=2 culture-positive samples. Time of antimicrobial treatment affected
      bacteriological cure for penicillin-sensitive Staph. aureus. Bacteriological cure
      tended to be higher for Staph. aureus after treatment at the first elevated CSCC
      compared with treatment at the second elevated CSCC. Thus, early treatment of
      Staph. aureus might be more effective than later treatment.

PMID- 20059921
TI  - Prediction of the herd somatic cell count of the following month using a linear
      mixed effect model.
AB  - An accurate prediction of the average somatic cell count (SCC) for the next month
      would be a valuable tool to support udder health management decisions. A linear
      mixed effect (LME) model was used to predict the average herd SCC (HSCC) for the
      following month. The LME model included data on SCC, herd characteristics,
      season, and management practices determined in a previous study that quantified
      the contribution of each factor for the HSCC. The LME model was tested on a new
      data set of 101 farms and included data from 3 consecutive years. The farms were
      split randomly in 2 groups of 50 and 51 farms. The first group of 50 farms was
      used to check for systematic errors in predicting monthly HSCC. An initial model
      was based on older data from a different part of the Netherlands and
      systematically overestimated HSCC in most months. Therefore, the model was
      adjusted for the difference in average HSCC between the 2 sets of farms (from the
      previous and current study) using the data from the first group of 50 farms.
      Subsequently, the data from the second group of 51 farms were used to
      independently assess this final model. A null model (no explanatory variables
      included) predicted 48 and 59% of the HSCC within the predetermined range of
      20,000 and 30,000 cells/mL, respectively. The final LME model predicted 72 and
      81% of the HSCC of the next month correctly within these 2 ranges. These outcomes
      indicate that the final LME model was a valid additional tool for farmers that
      could be useful in their short-term decisions regarding udder health management
      and could be included in dairy herd health programs.

PMID- 20059922
TI  - Forced heat loss from body surface reduces heat flow to body surface.
AB  - Heat stress is commonly relieved by forced evaporation from body surfaces. The
      mode of heat stress relief by heat extraction from the periphery is not clear,
      although it reduces rectal temperature. Radiant surface temperature (Ts) of the
      right half of the body surface was examined by thermovision in 4 lactating
      Holstein cows (30 kg of milk/d) during 7 repeated cycles of forced evaporation
      created by 30s of wetting followed by 4.5 min of forced airflow. Wetting was
      performed by an array of sprinklers (0.76 m(3)/h), and forced airflow (>3m/s
      velocity) over the right side of the body surface was produced by fans mounted at
      a height of 3m above the ground. Sprinkling wetted the hind legs, rump, and
      chest, but not the lower abdomen side, front legs, or neck. The animals were
      maintained in shade at an air temperature of 28 degrees C and relative humidity
      of 47%. Coat thickness was 1 to 2mm, so Ts closely represented skin temperature.
      Mean Ts of 5 x 20cm areas on the upper and lower hind and front legs, rump,
      chest, abdomen side, and neck were obtained by converting to temperature their
      respective gray intensity in single frames obtained at 10-s intervals. Little
      change occurred in Ts during the first wetting (0.1+/-0.6 degrees C), but it
      decreased rapidly thereafter (1.6+/-0.6 degrees C in the fifth wetting). The Ts
      also decreased, to a smaller extent, in areas that remained dry (0.7+/-1.0
      degrees C). In all body sites, a plateau in Ts was reached by 2 min after
      wetting. The difference between dry and wet areas in the first cooling cycle was
      approximately 1.2 degrees C. The Ts of different body areas decreased during
      consecutive cooling cycles and reached a plateau by 3 cooling cycles in dry sites
      (front leg, neck, abdomen side), by 5 cooling cycles in the hind leg, and 7
      cooling cycles in the rump and chest. The reduction in mean Ts produced by 7
      cycles was 4.0 to 6.0 degrees C in wetted areas and 1.6 to 3.7 degrees C in sites
      that were not wetted. Initial rectal temperature was 38.9+/-0.1 degrees C; it
      remained unchanged during first 5 cooling cycles, decreased by 0.1 degrees C
      after 7 cooling cycles, and decreased to 38.4+/-0.06 degrees C after 8 to 10
      cooling cycles, with no additional subsequent decrease. The concomitant reduction
      in Ts in dry and wet areas suggests an immediate vasoconstrictor response
      associated with heat extraction and later development of a cooler body shell. The
      reduction in rectal temperature represents a response involving transfer of heat
      from the body core to the body shell. This response mode requires consideration
      in settings of heat stress relief.

PMID- 20059923
TI  - On the use of physical activity monitoring for estrus detection in dairy cows.
AB  - Detection of estrus in dairy cattle is effectively aided by electronic activity
      tags or pedometers. Characterization of estrus intensity and duration is also
      possible from activity data. This study aimed to develop an algorithm to detect
      and characterize behavioral estrus from hourly recorded activity data and to
      apply the algorithm to activity data from an experimental herd. The herd
      comprised of Holstein (n=211), Jersey (n=126), and Red Dane (n=178) cattle, with
      virgin heifers (n=132) and lactating cows in the first 4 parities; n=895 cow
      parities, with a total of 3,674 activity episodes. The algorithm was based on
      deviations from exponentially smoothed hourly activity counts and was used to
      identify onset, duration, and intensity of estrus. Learning data included 461
      successful inseminations with activity records over a 2-wk period before and
      after the artificial insemination. Rates of estrus detection and error rate
      depended on the chosen threshold level. At a threshold giving 74.6% detection
      rate, daily error rate was 1.3%. When applied to a subset of the complete data
      where milk progesterone was also available, concordance of days to first activity
      detected estrus with the similar trait based on progesterone was also dependent
      on the chosen threshold so that, with stricter thresholds, the agreement was
      closer. A single-trait mixed model was used to determine the effects of
      systematic factors on the estrus activity traits. In general, an activity episode
      lasted 9.24h in heifers and 8.12h in cows, with the average strength of 1.03 ln
      units (equivalent to a 2.8-fold increase) in both age groups. Red Danes had
      significantly fewer days to first episode of high activity than Holsteins and
      Jerseys (29.4, 33.1, and 33.9 d, respectively). However, Jerseys had
      significantly shorter duration and less strength of estrus than both Red Danes
      and Holsteins of comparable age. The random effect of cow affected days to first
      episode of high activity and strength as well as estrus duration. Days from
      calving to first episode of high activity correlated negatively with body
      condition scores in early lactation. The results suggest that data from activity
      monitors could supply valuable information about fertility traits and could
      thereby be helpful in management of herd fertility. To establish the
      complementarities or interdependence between progesterone and activity
      measurements, further studies with more information from different sources of
      measuring estrus are needed.

PMID- 20059924
TI  - Short communication: transport of 2-hydroxy-4-methyl-thio-butanoic isopropyl
      ester by rumen epithelium in vitro.
AB  - Our objective was to evaluate the potential of rumen epithelium to transport 2
      hydroxy-4-(methylthio)-butanoic isopropyl ester (HMBi) using the Ussing chamber
      technique. Rumen tissues were obtained from a nearby slaughterhouse, separated
      from the muscle and serosal layer as quickly as possible after exsanguination,
      placed in buffer, and gassed with 95:5 (vol/vol) O(2):CO(2) before tissue
      mounting. Two levels of HMBi (0.44 and 0.88 mg/mL) and 2 incubation times (120
      and 180 min) were used in 12 chambers with 3 replicates per treatment with an
      exposed surface area of 2 cm(2). Four separate experiments were conducted (n=16).
      Concentrations of HMBi and methionine hydroxy analog (HMB) were measured by HPLC
      in rumen-side and serosal-side buffers. Data are expressed as percentage of added
      HMBi. Initial time samples were taken for comparison with incubated samples.
      Adding the HMBi-buffer mixture to the rumen side caused an immediate release of
      HMB (mean=6.3%). Breakdown of HMBi to HMB at initial time was due to hydrolysis
      reactions at the epithelial surface. Overall, a small and variable amount of HMBi
      was transferred to the serosal buffer (mean of 0.58% across both times and both
      concentrations). A larger amount of HMB (8.94%) was isolated in the serosal
      buffer. Increasing incubation time increased the amount of HMB in the ruminal
      buffer (34.0% at 120 min vs. 43.4% at 180 min) and decreased the amount of HMBi
      (37.9% at 120 min vs. 28.1% at 180 min). These data indicate that very limited
      amounts of HMBi may cross the rumen epithelium. The amount of HMB isolated on the
      serosal side was about 10 times higher than HMBi. The hydrolysis of HMBi to HMB
      required the presence of rumen tissue or perhaps microbes attached to the tissue.
      Based on this in vitro system, direct transport from the rumen would not explain
      rapid blood methionine increases observed when HMBi is fed.

PMID- 20059925
TI  - Shifts in bacterial community composition in the rumen of lactating dairy cows
      under milk fat-depressing conditions.
AB  - Eighteen ruminally cannulated dairy cattle were fed a series of diets (in 28-d
      periods) designed to elicit different degrees of milk fat depression (MFD) for
      the purpose of relating MFD to ruminal bacterial populations. Cows were fed a TMR
      containing 25% starch (DM basis) supplied as corn silage, a slowly fermented
      starch (SFS treatment, period 1), then switched to a TMR containing 27% starch,
      much of it supplied as ground high-moisture corn, a rapidly fermented starch (RFS
      treatment, period 2). In period 3, the RFS diet was amended with 13.6 mg of
      monensin/kg of DM (RFS/Mon treatment), and in period 4, the cows were returned to
      the RFS diet without monensin (RFS/Post treatment). Effect of both starch source
      and monensin on milk fat percentage varied by cow, and cluster analysis
      identified 4 pairs of cows having distinct milk fat patterns. Archived ruminal
      liquors and solids from the 4 pairs were processed to isolate bacterial DNA,
      which was subjected to automated ribosomal intergenic spacer analysis followed by
      correspondence analysis to visualize bacterial community composition (BCC). One
      pair of cows (S-responsive) showed MFD on RFS feeding, but displayed no
      additional MFD upon monensin feeding and a fat rebound upon monensin withdrawal.
      The second pair of cows (M-responsive) showed no MFD upon switch from the SFS
      diet to the RFS diet, but displayed strong MFD upon monensin feeding and no
      recovery after monensin withdrawal. Both groups displayed major shifts in BCC
      upon dietary shifts, including dietary shifts that both did and did not change
      milk fat production. The third pair of cows (SM-responsive) displayed reduction
      of milk fat on both RFS and RFS/Mon diets, and fat returned to the levels on the
      RFS diet upon monensin withdrawal; these cows showed a more gradual shift in BCC
      in response to both starch source and monensin. The fourth pair of cows
      (nonresponsive) did not display changes in milk fat percentage with dietary
      treatment and showed only minor shifts in BCC with dietary treatment. Regardless
      of milk fat response, BCC did not reassemble its original state upon monensin
      withdrawal, though the difference was strongest in M-responsive cows. One
      amplicon length (representing a single bacterial species) was elevated in most,
      but not all, MFD-susceptible (S-, M-, or SM-responsive) cows relative to milk fat
      nonresponsive cows, whereas 2 amplicon lengths displayed reduced abundance under
      MFD conditions. Overall, this study demonstrates an association between MFD and
      wholesale shifts of microbial communities in the rumen.

PMID- 20059926
TI  - pH dynamics and bacterial community composition in the rumen of lactating dairy
      cows.
AB  - The influence of pH dynamics on ruminal bacterial community composition was
      studied in 8 ruminally cannulated Holstein cows fitted with indwelling electrodes
      that recorded pH at 10-min intervals over a 54-h period. Cows were fed a silage
      based total mixed ration supplemented with monensin. Ruminal samples were
      collected each day just before feeding and at 3 and 6h after feeding. Solid and
      liquid phases were separated at collection, and extracted DNA was subjected to
      PCR amplification followed by automated ribosomal intergenic spacer analysis
      (ARISA). Although cows displayed widely different pH profiles (mean pH=6.11 to
      6.51, diurnal pH range=0.45 to 1.39), correspondence analysis of the ARISA
      profiles revealed that 6 of the 8 cows showed very similar bacterial community
      compositions. The 2 cows having substantially different community compositions
      had intermediate mean pH values (6.30 and 6.33) and intermediate diurnal pH
      ranges (averaging 0.89 and 0.81 pH units). Fortuitously, these 2 cows alone also
      displayed milk fat depression, along with markedly higher ruminal populations of
      1 bacterial operational taxonomic unit (OTU) and reduced populations of another
      ARISA amplicon. Cloning and sequencing of the elevated OTU revealed phylogenetic
      similarity to Megasphaera elsdenii, a species reportedly associated with milk fat
      depression. The higher populations of both M. elsdenii and OTU246 in these 2 cows
      were confirmed using quantitative real-time PCR (qPCR) with species-specific
      primers, and the fraction of total bacterial rDNA copies contributed by these 2
      taxa were very highly correlated within individual cows. By contrast, the
      fraction of total bacterial rDNA copies contributed by Streptococcus bovis and
      genus Ruminococcus, 2 taxa expected to respond to ruminal pH, did not differ
      among cows (mean= <0.01 and 10.6%, respectively, of rRNA gene copies, determined
      by qPCR). The data indicate that cows with widely differing pH profiles can have
      similar ruminal bacterial community compositions, and that milk fat depression
      can occur at intermediate ruminal pH. The results support recent reports that
      milk fat depression is associated with shifts in bacterial community composition
      in rumine and is specifically related to the relative abundance of Megasphaera
      elsdenii.

PMID- 20059927
TI  - Lactation performance and amino acid utilization of cows fed increasing amounts
      of reduced-fat dried distillers grains with solubles.
AB  - The use of a solvent-extraction process that removes corn oil from distillers
      grains produces a reduced-fat co-product (RFDG). To determine the optimal
      concentration of RFDG in mid-lactation diets, 22 multiparous and 19 primiparous
      Holstein cows were used in a completely randomized design for 8 wk, including a 2
      wk covariate period. The RFDG was included at 0, 10, 20, and 30% of the diet on a
      dry matter basis, replacing soybean feedstuffs. Increasing RFDG in diets had no
      effect on dry matter intake (23.1 kg/d) or milk production (35.0 kg/d). Milk fat
      percentage increased linearly from 3.18 to 3.72% as RFDG increased from 0 to 30%
      of the diet. Similarly, milk fat yield tended to increase linearly from 1.08 to
      1.32 kg/d. Milk protein percentage (2.99, 3.06, 3.13, and 2.99% for diets with
      RFDG from 0 to 30%) responded quadratically, whereas protein yield was not
      affected by treatment. Milk urea N decreased linearly from 15.8 to 13.1mg/dL. The
      efficiency of N utilization for milk production was not affected by including
      RFDG (26.1%), whereas the efficiency of milk production (energy-corrected milk
      divided by dry matter intake) tended to increase linearly with increasing RFDG in
      the diet. Similarly, concentrations of plasma glucose increased linearly.
      Arterial Lys decreased linearly from 66.0 to 44.8 microM/L, whereas arterial Met
      increased linearly from 16.5 to 29.3 microM/L. Arteriovenous difference of Lys
      decreased linearly from 42.6 to 32.5 microM/L, whereas that of Met was
      unaffected. The extraction of Lys by the mammary gland increased linearly from
      64.3 to 72.2%, whereas that of Met decreased linearly from 71.6 to 42.7%. Feeding
      up to 30% of RFDG in a mid-lactation diet supported lactation performance
      similarly to cows fed the soybean protein-based diet (0% RFDG).

PMID- 20059928
TI  - Association between bulk-tank milk Salmonella antibody level and high calf
      mortality in Danish dairy herds.
AB  - Salmonella enterica ssp. enterica Dublin is the most common Salmonella serotype
      found in the dairy sector in Denmark. Salmonella antibody level in bulk-tank milk
      (BTM), indicative of Salmonella Dublin infection in the herd, has been recorded
      regularly in all Danish dairy herds through a surveillance program since 2002.
      The objective of this study was to investigate whether high BTM Salmonella
      antibody level was associated with high calf mortality at herd level. Other risk
      factors for high calf mortality were also investigated: breed, production type
      (organic vs. conventional), number of animals purchased, herd size, and number of
      neighbor herds within a 4.9-km radius. Data from the Danish Cattle Database
      including the Salmonella surveillance program from September 2007 through August
      2008 were used. Dairy herds with more than 20 cows were included (n=4,337).
      Because of a highly right-skewed distribution of calf mortality with many zero
      values, calf mortality had to be dichotomized for the analysis. Therefore, in
      this study, high calf mortality was defined as calf mortality of more than 6.5%
      for calves aged 1 to 180 d. A logistic analysis was performed to identify risk
      factors associated with the probability of a herd having high calf mortality. The
      following factors were significantly associated with high calf mortality: high
      BTM Salmonella antibody level, odds ratio (OR)=2.0 (95% confidence interval=1.6
      2.4), organic production OR=1.4 (95% confidence interval=1.1-1.7) for organic
      versus conventional production, and breed. Purchase of 8 or more animals
      increased the OR of high calf mortality more than purchase of 1 to 7 animals,
      which again had a higher OR compared with purchase of 0 animals. Because only
      14.3% of the population consisted of herds with high BTM Salmonella status, the
      estimated proportion of herds with high calf mortality could only be reduced from
      38.7 to 36.5% by eradicating Salmonella from the Danish cattle population (i.e.,
      a population attributable risk of 2.2%). This showed that although there is a
      strong association between BTM Salmonella status and calf mortality, the problem
      with high calf mortality will not be solved by eradicating Salmonella. All other
      things equal, a population with more Salmonella-infected herds would gain a
      larger reduction in calf mortality from a Salmonella control campaign.
      Nevertheless, individual herds with a high within-herd prevalence of Salmonella
      are likely to benefit, both economically and regarding animal welfare, from
      controlling pathogenic Salmonella types in cattle.

PMID- 20059929
TI  - Carbohydrate source and protein degradability alter lactation, ruminal, and blood
      measures.
AB  - Thirty-eight lactating dairy cows including 6 ruminally cannulated cows were used
      in a feeding study to assess effects of feed sources that differed in dietary
      nonfiber carbohydrate (NFC) composition and ruminal degradability of dietary
      protein (RDP) on production, ruminal, and plasma measures. The design was a
      partially balanced, incomplete Latin square with three 21-d periods and a 3 x 2
      factorial arrangement of treatments. Samples and data were collected in the last
      7 d of each period. Feed sources that differed in NFC profile were dry ground
      corn (GC; starch), dried citrus pulp (DCP; sugar and pectins), and
      sucrose+molasses (SM; sugar). Dietary RDP was altered by providing CP with
      soybean meal (+RDP) or substituting a heat-treated expeller soybean product for a
      portion of the soybean meal (-RDP). Diets were formulated to be isonitrogenous
      and similar in NFC concentration. Cows consuming GC had the greatest milk urea
      nitrogen and milk protein percentage and yield, tended to have the greatest dry
      matter intake, but had a lesser milk fat percentage compared with cows consuming
      DCP and SM. Sucrose+molasses diets supported greater dry matter intake, milk
      protein yield, and 3.5% fat- and protein-corrected milk yield than did DCP diets.
      On -RDP diets, milk protein percentage was less and milk urea nitrogen and
      protein yield tended to be less than for +RDP diets. Dry ground corn diverged
      from DCP and SM in the effect of NFC x RDP, with cows consuming GC having lesser
      milk yield, 3.5% fat- and protein-corrected milk yield, and efficiency with -RDP
      as compared with +RDP, whereas these production measures were greater with -RDP
      than +RDP for cows consuming DCP and SM. In contrast, in situ NDF digestibility
      at 30h for GC and SM was greater for -RDP as compared with +RDP, but the reverse
      was true for DCP. The lowest ruminal pH detected by 6h postfeeding was also
      influenced by the interaction of NFC x RDP, with cows consuming SM having a lower
      pH with +RDP than with -RDP and cows consuming DCP having a similar pH on either
      RDP treatment. Total rumen volatile fatty acid concentrations did not differ
      among diets, but acetate molar percent was greater for DCP than for SM, and GC
      had the lowest molar percent for butyrate and valerate and greatest branched
      chain volatile fatty acid concentration. Valerate molar percent and NH(3)
      concentration tended to be greater with +RDP than with -RDP. Plasma glucose and
      insulin were both greater in cows receiving SM than in those receiving DCP.
      Protein degradability, NFC source, and their interactions affected lactation,
      ruminal, and blood measures, suggesting that these dietary factors warrant
      further consideration in diet formulation.

PMID- 20059930
TI  - Effective nitrogen preservation during urine collection from Holstein heifers fed
      diets with high or low protein content.
AB  - Six Holstein heifers (body weight=535-625 kg) fed a total mixed ration containing
      either high protein (13.4%) or low protein (9.0%) were used to evaluate the
      effect of 3 urine collection methods (chilled, acidified before collection, or
      acidified after 6h of collection) on urinary N preservation. In a 2-period
      crossover design, 16-d diet adjustment stages preceded five 24-h collections.
      Urinary catheters were inserted 1 d before the collection periods. Urine
      collection tubes were configured to split urine to 3 collection containers: 1
      acidified with 6 N HCl before collection at a rate calculated to reduce pH to
      below 2, 1 acidified every 6h during collection to pH below 2, and 1 located in a
      large cooler of ice. Collection method did not affect urinary concentration of N
      or urine urea-N (9.2+/-0.9 g/L and 6.58+/-0.9 g/L, respectively) or urinary
      excretion of N or urea-N (82+/-3.8 g/d and 59.5+/-3.8 g/d, respectively). These 3
      collection methods are equally effective in preserving N during urine collection,
      but the "chilled immediately" approach may be useful for studies focused on
      ammonia emission. Urinary and fecal N excretion were significantly different
      across collection days; fecal N was more highly variable than urinary N. Intake
      and apparent N digestibility decreased during the collection week, and excretion
      of urinary and fecal N increased, particularly on d 5. (Stable rectal
      temperatures suggested no urinary infections.) Improvements in total collection
      methodology will support continued progress in the understanding of livestock N
      utilization and post-excretion changes in manure N.

PMID- 20059932
TI  - Polymorphisms in the bovine leptin gene associated with perinatal mortality in
      Holstein-Friesian heifers.
AB  - Leptin is an important regulator of fetal and placental growth. This study
      evaluated the association of single nucleotide polymorphisms (SNP) in the leptin
      gene with perinatal mortality (stillbirths and mortality within 24h of
      parturition) in 385 Holstein-Friesian heifers on 18 dairy farms in the United
      Kingdom. The 3 SNP evaluated were exon 2FB, UASMS1, and UASMS2. The mean age at
      first calving was 27.0+/-0.2 mo. Associations between each SNP and perinatal
      mortality (calf alive or dead) were tested using a generalized linear model that
      included herd-year-season, calf sex, age at first calving, and age and pedigree
      of the dam. The overall level of perinatal mortality in the population was 16.9%,
      with significant allelic substitution effects for exon 2FB and UASMS1. These 2
      SNP were in close linkage disequilibrium with each other (r(2)=0.98) but not with
      UASMS2 (r(2)=0.10). For exon 2FB, perinatal mortality was similar between heifers
      carrying the CT and TT alleles (20%), but was higher than in heifers carrying the
      CC allele (11%). For UASMS1, mortality was 21% with the CC and CT alleles but
      only 10% with the TT allele. No associations of perinatal mortality with SNP were
      found in the UASMS2 data set, possibly influenced by the low frequency (2%) of
      the TT genotype. No significant effects of herd-year-season, age at first
      calving, or calf sex were found. In conclusion, polymorphisms in the leptin gene
      were associated with 2-fold differences in perinatal mortality in dairy heifers.

PMID- 20059931
TI  - Genetic determination of fatty acid composition in Spanish Churra sheep milk.
AB  - The objective of this study was to estimate the genetic variation of ovine milk
      fatty acid (FA) composition. We collected 4,100 milk samples in 14 herds from 976
      Churra ewes sired mostly by 15 AI rams and analyzed them by gas-liquid
      chromatography for milk fatty acid composition. The studied traits were 12
      individual FA contents (proportion in relation to the total amount of FA), 3
      groups of fatty acids [saturated fatty acids (SFA), monounsaturated FA (MUFA),
      and polyunsaturated FA (PUFA)], and 2 FA ratios (n-6:n-3 and C18:2 cis-9,trans
      11:C18:1 trans-11). In addition, percentages of fat and protein and daily milk
      yield were studied. For the analysis, repeatability animal models were
      implemented using Bayesian methods. In an initial step, univariate methods were
      conducted to test the hypothesis of the traits showing additive genetic
      determination. Deviance information criterion and Bayes factor were employed as
      model choice criteria. All the studied SFA showed additive genetic variance, but
      the estimated heritabilities were low. Among unsaturated FA (UFA), only C18:1
      trans-11 and C18:2 cis-9,cis-12 showed additive genetic variation, their
      estimated heritabilities being [marginal posterior mean (marginal posterior SD)]
      0.02(0.01) and 0.11(0.04), respectively. For the FA groups, only PUFA showed
      significant additive genetic variation. None of the studied ratios of FA showed
      additive genetic variation. In second multitrait analyses, genetic correlations
      between individual FA and production traits, and between groups of FA and ratios
      of FA and production traits, were investigated. Positive genetic correlations
      were estimated among medium-chain SFA, ranging from 0 to 0.85, but this parameter
      was close to zero between long-chain SFA (C16:0 and C18:0). Between long- and
      medium-chain SFA, estimated genetic correlations were negative, around -0.6.
      Among those UFA showing significant additive genetic variance, genetic
      correlations were close to zero. The estimated genetic correlations among all the
      investigated FA, milk yield, and fat and protein percentages were not different
      from zero. Our results suggest that low additive genetic variation is involved in
      the determination of the FA composition of milk fat in Churra sheep under current
      production conditions, which results in low values of heritabilities.

PMID- 20059933
TI  - Detection of quantitative trait loci affecting the milk fatty acid profile on
      sheep chromosome 22: role of the stearoyl-CoA desaturase gene in Spanish Churra
      sheep.
AB  - Sheep milk fat contains several components that may provide human health
      benefits, such as monounsaturated fatty acids and conjugated linoleic acid (CLA).
      Most of the CLA in ruminant milk is synthesized in the mammary gland by the
      action of the enzyme stearoyl-CoA desaturase (SCD) on circulating vaccenic acid
      (trans-11 C18:2; VA). Previous studies have found significant associations
      between polymorphisms in the SCD gene and the fatty acid composition of ruminant
      products, including sheep milk. Based on this, we performed a quantitative trait
      loci (QTL) analysis of an ovine chromosome (22) that harbors the SCD gene for
      effects on milk fatty acid composition traits and classical milk production
      traits. We identified a suggestive QTL influencing the CLA/VA ratio with the
      maximum statistic at position 26 cM of the studied chromosome, whereas the SCD
      gene has been mapped to position 41.6 cM. The individual introduction of 4 SCD
      single nucleotide polymorphisms in the QTL model did not cause a reduction of the
      variance explained by the QTL, which suggests that the SCD gene is not directly
      responsible for the detected effect in the Churra population studied herein. This
      conclusion was supported by the lack of any significant association identified
      between the 4 SCD single nucleotide polymorphisms and the CLA/VA ratio. This
      association analysis suggested a possible effect of the SCD gene on milk fat
      percentage in Churra sheep. An independent confirmation of these primary results
      will be required before attempting its practical implementation in selection
      programs.

PMID- 20059934
TI  - Economic values and expected effect of selection index for pathogen-specific
      mastitis under Danish conditions.
AB  - The objectives of this study were 1) to estimate costs related to 5 different
      pathogen-specific mastitis traits (susceptibility to different pathogens causing
      mastitis in dairy cattle) and unspecific mastitis, and 2) to compare selection
      differentials for an udder health index consisting of 5 different pathogen
      specific mastitis traits and lactation average somatic cell count from 5 to 170 d
      after first calving (LASCC170) with another index consisting of 1 unspecific
      mastitis trait and LASCC170. Economic values were estimated for mastitis caused
      by Staphylococcus aureus, Streptococcus dysgalactiae, Escherichia coli, coagulase
      negative staphylococci, and Streptococcus uberis using a stochastic simulation
      model (SimHerd IV). Mastitis incidences for SimHerd IV were from incidences of
      mastitis treatments in primiparous Danish Holstein cows calving in 2007.
      Estimated costs ranged from 149 euro to 570 euro per mastitis case and were
      highest for contagious pathogens such as Staph. aureus and coagulase-negative
      staphylococci and lowest for Strep. dysgalactiae and Strep. uberis. The value for
      unspecific mastitis was 231 euro per case. Selection differentials (in euro) were
      estimated for 4 different selection indices, including 1) unspecific mastitis, 2)
      unspecific mastitis and LASCC170, 3) 5 pathogen-specific mastitis traits and
      unspecific residual mastitis (unspecific mastitis treatments minus mastitis
      treatments caused by the 5 pathogens), and 4) as index 3 including LASCC170. The
      breeding goal was identical to selection index 3. Mastitis data from primiparous
      cows calving from 1998 to 2008 were used to estimate genetic parameters of the
      mastitis traits using linear models and AI-REML algorithm. These parameters were
      used for construction of the selection index equations. For the selection
      indices, information sources were measurements of mastitis treatments and
      LASCC170 from 50, 80, or 130 daughters of a bull as well as measurements of
      mastitis treatments from 1,000 progeny of the bull's sire and 1,000 daughters of
      his maternal grandsire. Differences in selection differentials were marginal
      among the 4 indices. Without considering LASCC170, the selection differential of
      an unspecific mastitis index was 0.4 euro (<1%) better than that of a pathogen
      specific index. On the other hand, the selection differential of the pathogen
      specific index was 0.3 euro (<1%) better than that of an unspecific index when
      LASCC170 was included in the indices. Reliabilities of the selection indices were
      0.62 to 0.67 (80 daughters) and were proportional to the selection differential.
      Changing the number of daughters to 50 or 130 did not change ranking of the
      indices. Heritabilities of the pathogen-specific traits were very low (h(2)=0.005
      0.021) compared with unspecific mastitis (h(2)=0.062), which may limit the
      selection differential of the pathogen-specific index.

PMID- 20059935
TI  - Short communication: genetic and environmental relationships between milk yield
      and kidding interval in dairy goats.
AB  - First-parity 305-d milk yield and intervals between first and second kiddings
      from 1975 through 2005 were analyzed to estimate genetic and environmental
      parameters for United States Alpine, LaMancha, Nubian, Saanen, and Toggenburg
      dairy goats. The data set included 43,612 does with first-parity milk yield and
      25,863 does with first kidding interval. Parameters were estimated by REML using
      bivariate mixed models within and across breeds. Fixed effects were month and
      herd-year of kidding within breed and month and breed-herd-year of kidding across
      breeds. Random effects were animal and residual. The heritability estimate for
      first-parity milk yield was 0.36+/-0.01 across breeds and ranged from 0.35 to
      0.38 within breed; heritability for first kidding interval was 0.05+/-0.01 across
      breeds and ranged from 0.00 to 0.15 within breed. The estimate of the genetic
      correlation between first-parity milk yield and first kidding interval was
      positive (unfavorable) across breeds (0.35+/-0.09). Estimates of environmental
      correlations within and across breeds were positive (0.16-0.25). The presence of
      unfavorable genetic relationships between milk yield and kidding interval
      indicates a need to include reproductive performance as a selection criterion.

PMID- 20059936
TI  - Conceptual modeling of postmortem evaluation findings to describe dairy cow
      deaths.
AB  - Dairy cow mortality levels in the United States are excessive and increasing over
      time. To better define cause and effect and combat rising mortality, clearer
      definitions of the reasons that cows die need to be acquired through thorough
      necropsy-based postmortem evaluations. The current study focused on organizing
      information generated from postmortem evaluations into a monitoring system that
      is based on the fundamentals of conceptual modeling and that will potentially be
      translatable into on-farm relational databases. This observational study was
      conducted on 3 high-producing, commercial dairies in northern Colorado.
      Throughout the study period a thorough postmortem evaluation was performed by
      veterinarians on cows that died on each dairy. Postmortem data included necropsy
      findings, life-history features (e.g., birth date, lactation number, lactational
      and reproductive status), clinical history and treatments, and pertinent aspects
      of operational management that were subject to change and considered integral to
      the poor outcome. During this study, 174 postmortem evaluations were performed.
      Postmortem evaluation results were conceptually modeled to view each death within
      the context of the web of factors influencing the dairy and the cow. Categories
      were formulated describing mortality in terms of functional characteristics
      potentially amenable to easy performance evaluation, management oversight, and
      research. In total, 21 death categories with 7 category themes were created.
      Themes included specific disease processes with variable etiologies, failure of
      disease recognition or treatment, traumatic events, multifactorial failures
      linked to transition or negative energy balance issues, problems with feed
      management, miscellaneous events not amenable to prevention or treatment, and
      undetermined causes. Although postmortem evaluations provide the relevant
      information necessary for framing a cow's death, a restructuring of on-farm
      databases is needed to integrate this level of detail into useful monitoring
      systems. Individual operations can focus on combating mortality through the use
      of employee training related to postmortem evaluations, detailed forms for
      capturing necropsy particulars and other relevant information related to deaths,
      and standardized nomenclature and categorization schemes. As much as anything,
      the simple act of recognizing mortality as a problem might be the most
      fundamental step toward controlling its progression.

PMID- 20059937
TI  - Determinants of technical efficiency among dairy farms in Wisconsin.
AB  - The US dairy sector is facing structural changes including a geographical shift
      in dairy production and a tendency toward the implementation of more intensive
      production systems. These changes might significantly affect farm efficiency,
      profitability, and the long-term economic sustainability of the dairy sector,
      especially in more traditional dairy production areas. Consequently, the goal of
      this study was to examine the effect of practices commonly used by dairy farmers
      and the effect of intensification on the performance of the farms. We used a
      sample of 273 Wisconsin dairy farms to estimate a stochastic production frontier
      simultaneously with a technical inefficiency model. The empirical analysis showed
      that at a commercial level the administration of bovine somatotropin hormone to
      lactating cows increased milk production. In addition, we found that production
      exhibits constant returns to scale and that farm efficiency is positively related
      to farm intensification, the level of contribution of family labor in the farm
      activities, the use of a total mixed ration feeding system, and milking
      frequency.

PMID- 20059938
TI  - A large Markovian linear program to optimize replacement policies and dairy herd
      net income for diets and nitrogen excretion.
AB  - The purpose of the study was 2-fold: 1) to propose a novel modeling framework
      using Markovian linear programming to optimize dairy farmer-defined goals under
      different decision schemes and 2) to illustrate the model with a practical
      application testing diets for entire lactations. A dairy herd population was
      represented by cow state variables defined by parity (1 to 15), month in
      lactation (1 to 24), and pregnancy status (0 nonpregnant and 1 to 9 mo of
      pregnancy). A database of 326,000 lactations of Holsteins from AgSource Dairy
      Herd Improvement service (http://agsource.crinet.com/page249/DHI) was used to
      parameterize reproduction, mortality, and involuntary culling. The problem was
      set up as a Markovian linear program model containing 5,580 decision variables
      and 8,731 constraints. The model optimized the net revenue of the steady state
      dairy herd population having 2 options in each state: keeping or replacing an
      animal. Five diets were studied to assess economic, environmental, and herd
      structural outcomes. Diets varied in proportions of alfalfa silage (38 to 98% of
      dry matter), high-moisture ear corn (0 to 42% of dry matter), and soybean meal (0
      to 18% of dry matter) within and between lactations, which determined dry matter
      intake, milk production, and N excretion. Diet ingredient compositions ranged
      from one of high concentrates to alfalfa silage only. Hence, the model identified
      the maximum net revenue that included the value of nutrient excretion and the
      cost of manure disposal associated with the optimal policy. Outcomes related to
      optimal solutions included the herd population structure, the replacement policy,
      and the amount of N excreted under each diet experiment. The problem was solved
      using the Excel Risk Solver Platform with the Standard LP/Quadratic Engine.
      Consistent replacement policies were to (1) keep pregnant cows, (2) keep
      primiparous cows longer than multiparous cows, and (3) decrease replacement rates
      when milk and feed prices are favorable. The optimal policy called for the
      replacement of open cows between 7 and 12 mo in lactation depending on parity,
      diet, and market conditions. Under favorable market conditions, net revenue was
      greatest with the greatest concentrate diet, which was $15.24 and $52.32/mo per
      cow greater than the optimal net revenue realized with the intermediate and the
      no-concentrate (all-forage) diets, respectively. A suboptimal solution to limit
      the N excretion to 12 kg/mo per cow when market conditions were favorable
      resulted in a diet with the second-greatest amount of concentrates being the one
      with the greatest net revenue. Under unfavorable market conditions, the diet with
      the greatest concentrate content had the least net revenue compared with all the
      others. A suboptimal solution for a maximum N excretion of 12 kg/mo per cow with
      unfavorable market conditions resulted in the least-concentrate diet having the
      greatest net revenue ($22/mo per cow), followed by the second-greatest
      concentrate diet ($20/mo per cow) and the all-forage diet ($18/mo per cow). The
      implementation of a Markovian linear program for dairy decision making provides
      both robustness and versatility in operations research. The model could become a
      valuable tool for economic decision making for dairy farms.

PMID- 20059939
TI  - Manure nutrient excretion by Jersey and Holstein cows.
AB  - The objective of this study was to evaluate feces, urine, and N excretion by
      Jersey and Holstein cows. Sixteen multiparous cows (n=8 per breed) were fed 2
      experimental rations at calving in a switchback experimental design. Diets were
      50% forage and based on corn meal (control) or whole cottonseed. Half the cows in
      each breed started on the control diet and half started on the whole cottonseed
      diet. Cows were switched to the other diet at 60 d in milk and switched back to
      their original diet at 165 d in milk. Pairs of cows were moved into open-circuit
      respiration chambers on d 49, 154, and 271 of lactation for 7-d measurement
      periods. While in the chambers, total collection of feed refusals, milk,
      recovered hair, feces, and urine was conducted. No effect of the interaction of
      diet and breed was observed for measures of nutrient digestibility and manure
      excretion. Total daily manure excretion was lower in Jersey cows than in Holstein
      cows, with reductions generally proportional to changes in feed intake. Jersey
      cows consumed 29% less feed and excreted 33% less wet feces and 28% less urine
      than Holstein cows. Intake, fecal, and urinary N were reduced by 29, 33, and 24%,
      respectively, in Jersey cows compared with Holstein cows. Equations from American
      Society of Agricultural and Biological Engineers underpredicted observed values
      for all manure measures evaluated (urine, manure solids, N, wet manure), and
      breed bias was observed in equations predicting excretion of urine, N, and wet
      manure. Although these equations include animal and dietary factors, intercepts
      of regression of observed values on predicted values differed between Holsteins
      and Jerseys for those 3 measures. No breed bias was observed in the prediction of
      manure solids excretion, however, making that equation equally appropriate for
      Jerseys and Holsteins. The effect of breed on manure and nutrient excretion has
      significant nutrient management implications.

PMID- 20059940
TI  - Optimizing weaning strategies of dairy replacement calves.
AB  - Two experiments were conducted to evaluate whether performance could be improved
      and incidence of respiratory problems decreased either by allocating 6 additional
      days of individual housing after weaning or by moving calves in groups before
      weaning at 2 different ages. The first experiment involved 320 female calves that
      received 2L of milk replacer (MR) twice daily until 49 d of age, and then 2L of
      MR once daily until weaning at 56 d of age. Half of the calves were allowed to
      remain individually housed for an additional 6d after weaning, and the other half
      were moved immediately after weaning to a different pen holding 8 calves. The
      second experiment involved 240 female calves that received 2L of MR twice daily
      until 49 d of age, and then 2L of MR once daily. Half of the calves were moved at
      49 d of age to superhutches holding 8 calves with an elevated trough that was
      used to continue delivering MR; the other half remained individually housed until
      the age of 56d and were then moved to the superhutches, where they also continued
      to receive MR. Growth and incidence of respiratory problems were recorded in both
      experiments, and feed intake was recorded in experiment 2. Calves moved to groups
      immediately after weaning reached the target BW 6d earlier and experienced a
      lesser incidence of respiratory afflictions than those grouped 6d after weaning.
      From experiment 2, calves grouped at 49 d of age had a greater average daily gain
      and BW at 56 d of age as a result of a greater total solid feed consumption
      compared with those grouped at 56 d of age. Calves grouped at 56 d, however, had
      a greater average daily gain between 56 and 64 d of age (the week following
      grouping for the calves in the 56-d treatment) than those grouped at 49 d of age.
      Overall, the proportion of animals affected by a respiratory problem between 49
      and 112 d of age did not differ between treatments. However, calves grouped at 49
      d of age had a lower number of respiratory cases than those grouped at 56 d of
      age. It is concluded that moving calves from individual hutches to groups of
      calves in superhutches immediately after weaning is preferable to waiting an
      additional 6d. In addition, moving calves from individual hutches to groups of 8
      in superhutches at 49 d of age and starting to reduce MR offering once grouped is
      preferable to starting to reduce MR while calves are individually housed.

PMID- 20059941
TI  - Effect of synchronization and semen sorting on artificial insemination bull
      fertility.
AB  - Field data were collected over a period of 2 yr by artificial insemination
      technicians for the purpose of evaluating differences among bulls in their
      fertility when synchronization and semen sorting were involved. First, main
      effects of synchronization and semen sorting were found to reduce bull fertility
      by 1.5 and 12.7%, respectively. Second, the interaction of both factors with bull
      fertility significantly enhanced the evaluation models. Differences between 2
      sets of adjusted conception rates for synchronized and nonsynchronized services
      ranged from 0.5 to 2.9%, whereas differences between 2 sets of adjusted
      conception rates for sorted and conventional semen ranged from -1.8 to 15.2%.
      This implies that using conventional fertility models that ignore these effects
      may not be sufficiently accurate in situations where synchronization or semen
      sorting are involved. Accounting for synchronization and especially for semen
      sorting to evaluate bulls on their fertility and the production of separate sets
      of conception rates under each situation are essential.

PMID- 20059942
TI  - Defending the genome in tudor style.
AB  - Repression of transposable elements is crucial for the survival of germ cells. In
      this issue of Developmental Cell, Shoji et al. provide evidence that a Tudor
      domain protein TDRD9 partners with MIWI2 to specifically silence LINE-1
      transposons in the fetal germline of male mice.

PMID- 20059943
TI  - The EmERgence of autophagosomes.
AB  - Autophagosomes are large double-membrane vesicles that enclose cytoplasmic
      components targeting them for degradation. Two recent reports reveal that
      phagophores, the autophagosome precursors, are surrounded by and connected to
      rough endoplasmic reticulum (ER) membranes. These results shed light on how
      membranes may be supplied and reorganized for autophagosomal biogenesis.

PMID- 20059944
TI  - Wnt signaling in mitosis.
AB  - Previously, the connection between cell proliferation and Wnt signaling focused
      on transcriptional activation of cyclin D1 and c-myc, which control the G1/S
      transition of the cell cycle. In this issue of Developmental Cell, the Niehrs
      group demonstrates mitotic activation of Wnt signaling by a novel Cdk/cyclin
      complex containing Cdk14 (PFTK1) and cyclin Y.

PMID- 20059945
TI  - Outsmarting a mastermind.
AB  - Moellering et al. recently reported that a cell-permeable "stapled" synthetic
      peptide of the Notch coactivator Mastermind is a potent dominant-negative
      inhibitor of oncogenic Notch signaling in T cell acute lymphoblastic leukemia.
      This new class of inhibitor may find broad utility in blocking protein-protein
      interactions that underlie many human diseases.

PMID- 20059946
TI  - TTC3 ubiquitination terminates Akt-ivation.
AB  - In this issue of Developmental Cell, Suizu et al. (2009) describe a new mechanism
      for posttranslational regulation of the Akt serine/threonine protein kinase
      involving ubiquitination. They show that the E3 ubiquitin ligase TTC3 modifies
      phosphorylated and activated Akt and thereby promotes its degradation by the
      proteasome in the nucleus.

PMID- 20059947
TI  - The role of hypoxia in development of the Mammalian embryo.
AB  - Hypoxia inducible factor (HIF) is a transcription factor that acts in low-oxygen
      conditions. The cellular response to HIF activation is transcriptional
      upregulation of a large group of genes. Some target genes promote anaerobic
      metabolism to reduce oxygen consumption, while others "alleviate" hypoxia by
      acting non-cell-autonomously to extend and modify the surrounding vasculature.
      Although hypoxia is often thought of as being a pathological phenomenon, the
      mammalian embryo in fact develops in a low-oxygen environment, and in this
      context HIF has additional responsibilities. This review describes how low oxygen
      and HIF affect gene expression, cell behavior, and ultimately morphogenesis of
      the embryo and placenta.

PMID- 20059948
TI  - The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing
      in the mouse male germline.
AB  - Host-defense mechanisms against transposable elements are critical to protect the
      genome information. Here we show that tudor-domain containing 9 (Tdrd9) is
      essential for silencing Line-1 retrotransposon in the mouse male germline. Tdrd9
      encodes an ATPase/DExH-type helicase, and its mutation causes male sterility
      showing meiotic failure. In Tdrd9 mutants, Line-1 was highly activated and piwi
      interacting small RNAs (piRNAs) corresponding to Line-1 were increased,
      suggesting that feedforward amplification operates in the mutant. In fetal
      testes, Tdrd9 mutation causes Line-1 desilencing and an aberrant piRNA profile in
      prospermatogonia, followed by cognate DNA demethylation. TDRD9 complexes with
      MIWI2 with distinct compartmentalization in processing bodies, and this TDRD9
      MIWI2 localization is regulated by MILI and TDRD1 residing at intermitochondrial
      cement. Our results identify TDRD9 as a functional partner of MIWI2 and indicate
      that the tudor-piwi association is a conserved feature, while two separate axes,
      TDRD9-MIWI2 and TDRD1-MILI, cooperate nonredundantly in the piwi-small RNA
      pathway in the mouse male germline.

PMID- 20059949
TI  - Cell cycle control of wnt receptor activation.
AB  - Low-density lipoprotein receptor related proteins 5 and 6 (LRP5/6) are
      transmembrane receptors that initiate Wnt/beta-catenin signaling. Phosphorylation
      of PPPSP motifs in the LRP6 cytoplasmic domain is crucial for signal
      transduction. Using a kinome-wide RNAi screen, we show that PPPSP phosphorylation
      requires the Drosophila Cyclin-dependent kinase (CDK) L63. L63 and its vertebrate
      homolog PFTK are regulated by the membrane tethered G2/M Cyclin, Cyclin Y, which
      mediates binding to and phosphorylation of LRP6. As a consequence, LRP6
      phosphorylation and Wnt/beta-catenin signaling are under cell cycle control and
      peak at G2/M phase; knockdown of the mitotic regulator CDC25/string, which
      results in G2/M arrest, enhances Wnt signaling in a Cyclin Y-dependent manner. In
      Xenopus embryos, Cyclin Y is required in vivo for LRP6 phosphorylation, maternal
      Wnt signaling, and Wnt-dependent anteroposterior embryonic patterning. G2/M
      priming of LRP6 by a Cyclin/CDK complex introduces an unexpected new layer of
      regulation of Wnt signaling.

PMID- 20059950
TI  - The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated
      Akt.
AB  - The serine threonine kinase Akt is a core survival factor that underlies a
      variety of human diseases. Although regulatory phosphorylation and
      dephosphorylation have been well documented, the other posttranslational
      mechanisms that modulate Akt activity remain unclear. We show here that
      tetratricopeptide repeat domain 3 (TTC3) is an E3 ligase that interacts with Akt.
      TTC3 contains a canonical RING finger motif, a pair of tetratricopeptide motifs,
      a putative Akt phosphorylation site, and nuclear localization signals, and is
      encoded by a gene within the Down syndrome (DS) critical region on chromosome 21.
      TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and
      facilitates its ubiquitination and degradation within the nucleus. Moreover, DS
      cells exhibit elevated TTC3 expression, reduced phosphorylated Akt, and
      accumulation in the G(2)M phase, which can be reversed by TTC3 siRNA or Myr-Akt.
      Thus, interaction between TTC3 and Akt may contribute to the clinical symptoms of
      DS.

PMID- 20059951
TI  - Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic
      clathrin-coated pits.
AB  - The GTPase dynamin, a key player in endocytic membrane fission, interacts with
      numerous proteins that regulate actin dynamics and generate/sense membrane
      curvature. To determine the functional relationship between these proteins and
      dynamin, we have analyzed endocytic intermediates that accumulate in cells that
      lack dynamin (derived from dynamin 1 and 2 double conditional knockout mice). In
      these cells, actin-nucleating proteins, actin, and BAR domain proteins accumulate
      at the base of arrested endocytic clathrin-coated pits, where they support the
      growth of dynamic long tubular necks. These results, which we show reflect the
      sequence of events in wild-type cells, demonstrate a concerted action of these
      proteins prior to, and independent of, dynamin and emphasize similarities between
      clathrin-mediated endocytosis in yeast and higher eukaryotes. Our data also
      demonstrate that the relationship between dynamin and actin is intimately
      connected to dynamin's endocytic role and that dynamin terminates a powerful
      actin- and BAR protein-dependent tubulating activity.

PMID- 20059952
TI  - Dual modes of cdc42 recycling fine-tune polarized morphogenesis.
AB  - In budding yeast, the highly conserved small GTPase Cdc42 localizes to the cortex
      at a cell pole and orchestrates the trafficking and deposition of cell surface
      materials required for building a bud or mating projection (shmoo). Using a
      combination of quantitative imaging and mathematical modeling, we elucidate
      mechanisms of dynamic recycling of Cdc42 that balance diffusion. Rdi1, a guanine
      nucleotide dissociation inhibitor (GDI), mediates a fast recycling pathway, while
      actin patch-mediated endocytosis accounts for a slower one. These recycling
      mechanisms are restricted to the same region of the nascent bud, as both are
      coupled to the Cdc42 GTPase cycle. We find that a single dynamic parameter, the
      rate of internalization inside the window of polarized delivery, is tuned to give
      rise to distinct shapes of Cdc42 distributions that correlate with distinct
      morphogenetic fates, such as the formation of a round bud or a pointed shmoo.

PMID- 20059953
TI  - A systems approach reveals that the myogenesis genome network is regulated by the
      transcriptional repressor RP58.
AB  - We created a whole-mount in situ hybridization (WISH) database, termed EMBRYS,
      containing expression data of 1520 transcription factors and cofactors expressed
      in E9.5, E10.5, and E11.5 mouse embryos--a highly dynamic stage of skeletal
      myogenesis. This approach implicated 43 genes in regulation of embryonic
      myogenesis, including a transcriptional repressor, the zinc-finger protein RP58
      (also known as Zfp238). Knockout and knockdown approaches confirmed an essential
      role for RP58 in skeletal myogenesis. Cell-based high-throughput transfection
      screening revealed that RP58 is a direct MyoD target. Microarray analysis
      identified two inhibitors of skeletal myogenesis, Id2 and Id3, as targets for
      RP58-mediated repression. Consistently, MyoD-dependent activation of the myogenic
      program is impaired in RP58 null fibroblasts and downregulation of Id2 and Id3
      rescues MyoD's ability to promote myogenesis in these cells. Our combined, multi
      system approach reveals a MyoD-activated regulatory loop relying on RP58-mediated
      repression of muscle regulatory factor (MRF) inhibitors.

PMID- 20059954
TI  - Pancreatic exocrine duct cells give rise to insulin-producing beta cells during
      embryogenesis but not after birth.
AB  - A longstanding unsettled question is whether pancreatic beta cells originate from
      exocrine duct cells. We have now used genetic labeling to fate map embryonic and
      adult pancreatic duct cells. We show that Hnf1beta+ cells of the trunk
      compartment of the early branching pancreas are precursors of acinar, duct, and
      endocrine lineages. Hnf1beta+ cells subsequent form the embryonic duct
      epithelium, which gives rise to both ductal and endocrine lineages, but not to
      acinar cells. By the end of gestation, the fate of Hnf1beta+ duct cells is
      further restrained. We provide compelling evidence that the ductal epithelium
      does not make a significant contribution to acinar or endocrine cells during
      neonatal growth, during a 6 month observation period, or during beta cell growth
      triggered by ligation of the pancreatic duct or by cell-specific ablation with
      alloxan followed by EGF/gastrin treatment. Thus, once the ductal epithelium
      differentiates it has a restricted plasticity, even under regenerative settings.

PMID- 20059955
TI  - Bone ridge patterning during musculoskeletal assembly is mediated through SCX
      regulation of Bmp4 at the tendon-skeleton junction.
AB  - During the assembly of the musculoskeletal system, bone ridges provide a stable
      anchoring point and stress dissipation for the attachment of muscles via tendons
      to the skeleton. In this study, we investigate the development of the deltoid
      tuberosity as a model for bone ridge formation. We show that the deltoid
      tuberosity develops through endochondral ossification in a two-phase process:
      initiation is regulated by a signal from the tendons, whereas the subsequent
      growth phase is muscle dependent. We then show that the transcription factor
      scleraxis (SCX) regulates Bmp4 in tendon cells at their insertion site. The
      inhibition of deltoid tuberosity formation and several other bone ridges in
      embryos in which Bmp4 expression was blocked specifically in Scx-expressing cells
      implicates BMP4 as a key mediator of tendon effects on bone ridge formation. This
      study establishes a mechanistic basis for tendon-skeleton regulatory interactions
      during musculoskeletal assembly and bone secondary patterning.

PMID- 20059956
TI  - A Drosophila insulin-like peptide promotes growth during nonfeeding states.
AB  - In metazoans, tissue growth relies on the availability of nutrients--stored
      internally or obtained from the environment--and the resulting activation of
      insulin/IGF signaling (IIS). In Drosophila, growth is mediated by seven
      Drosophila insulin-like peptides (Dilps), acting through a canonical IIS pathway.
      During the larval period, animals feed and Dilps produced by the brain couple
      nutrient uptake with systemic growth. We show here that, during metamorphosis,
      when feeding stops, a specific DILP (Dilp6) is produced by the fat body and
      relays the growth signal. Expression of DILP6 during pupal development is
      controlled by the steroid hormone ecdysone. Remarkably, DILP6 expression is also
      induced upon starvation, and both its developmental and environmental expression
      require the Drosophila FoxO transcription factor. This study reveals a specific
      class of ILPs induced upon metabolic stress that promotes growth in conditions of
      nutritional deprivation or following developmentally induced cessation of
      feeding.

PMID- 20059957
TI  - A fat body-derived IGF-like peptide regulates postfeeding growth in Drosophila.
AB  - Members of the insulin family of peptides have conserved roles in the regulation
      of growth and metabolism in a wide variety of metazoans. Here we show that
      Drosophila insulin-like peptide 6 (DILP6), which is structurally similar to
      vertebrate insulin-like growth factor (IGF), is predominantly expressed in the
      fat body, a functional equivalent of the vertebrate liver and adipocytes. This
      expression occurs during the postfeeding stage under the direct regulation of
      ecdysteroid. We further reveal that dilp6 mutants show growth defects during the
      postfeeding stage, which results in reduced adult body size through a decrease in
      cell number. This phenotype is rescued by fat body-specific expression of dilp6.
      These data indicate that DILP6 is a functional, as well as a structural,
      counterpart of vertebrate IGFs. Our data provide in vivo evidence for a role of
      ILPs in determining adult body size through the regulation of postfeeding growth.

PMID- 20059958
TI  - Pax3:Foxc2 reciprocal repression in the somite modulates muscular versus vascular
      cell fate choice in multipotent progenitors.
AB  - Maintenance of multipotency and how cells exit this state to adopt a specific
      fate are central questions in stem cell biology. During vertebrate development,
      multipotent cells of the dorsal somite, the dermomyotome, give rise to different
      lineages such as vascular smooth and skeletal muscle, regulated by the
      transcription factors Foxc2 and Pax3, respectively. Here we show reciprocal
      inhibition between Pax3 and Foxc2 in the mouse embryo. Using both genetic
      approaches and manipulation of external signals in somite explants, we
      demonstrate that the Pax3:Foxc2 ratio modulates myogenic versus vascular cell
      fates. This provides insight into how cell fate choices are orchestrated by these
      lineage genes in the dermomyotome.

PMID- 20059959
TI  - Phosphorylation of SAS-6 by ZYG-1 is critical for centriole formation in C.
      elegans embryos.
AB  - Despite being essential for proper cell division, the mechanisms governing
      centrosome duplication are incompletely understood and represent an important
      open question in cell biology. Formation of a new centriole next to each existing
      one is critical for centrosome duplication. In Caenorhabditis elegans embryos,
      the proteins SPD-2, ZYG-1, SAS-6, SAS-5, and SAS-4 are essential for centriole
      formation, but the mechanisms underlying their requirement remain unclear. Here,
      we demonstrate that the kinase ZYG-1 phosphorylates the coiled-coil protein SAS-6
      at serine 123 in vitro. Importantly, we show that this phosphorylation event is
      crucial for centriole formation in vivo. Furthermore, we establish that such
      phosphorylation ensures the maintenance of SAS-6 at the emerging centriole.
      Overall, our findings establish that phosphorylation of the evolutionarily
      conserved protein SAS-6 is critical for centriole formation and thus for faithful
      cell division.

PMID- 20059960
TI  - Reciprocal regulation of natriuretic peptide receptors by insulin in adipose
      cells.
AB  - Atrial- and brain-type natriuretic peptides (ANP and BNP, respectively) have been
      shown to exert potent lipolytic action in adipocytes. A family of natriuretic
      peptide receptors (NPRs), NPR-1, NPR-2, and NPR-3, mediates their physiologic
      effects. NPR-1 and NPR-2 are receptor guanylyl cyclases, while NPR-3 lacks
      enzymatic activity and functions primarily as a clearance receptor for
      natriuretic peptides. ANP has a high affinity for NPR-1 and NPR-3 than other
      natriuretic peptides. There is a possibility that ANP may exhibit its lipolytic
      effect through the balance of NPR-1 and NPR-3 expressions in adipocytes. However,
      the regulation of adipose NPRs has not been fully elucidated. We here examined
      the regulation of mouse adipose NPRs by insulin, an anti-lipolytic hormone. Among
      the insulin target organs, NPR-1 mRNA levels were higher in white adipose tissue
      (WAT) than in liver and skeletal muscle. NPR-3 mRNA was expressed most abundantly
      in WAT. Fasting condition induced NPR-1 mRNA level while suppressed NPR-3 mRNA
      level in WAT. Administration of streptozotocin resulted in the increase of NPR-1
      mRNA level while the decrease of NPR-3 mRNA level in WAT. In ob/ob mice,
      hyperinsulinemic model, NPR-1 mRNA level was lower whereas NPR-3 mRNA level was
      higher compared to lean control mice. In 3T3-L1 adipocytes, insulin significantly
      reduced NPR-1 mRNA level while increased NPR-3 mRNA levels both through
      phosphatidylinositol 3-kinase (PI3-kinase) pathway. In summary, NPR-1 and NPR-3
      were highly expressed in WAT and adipose NPR-1 and NPR-3 were reciprocally
      regulated by insulin. This study suggests that insulin may efficiently promote
      lipogenesis partly by reducing the lipolytic action of ANP through the opposite
      regulation of NPR-1 and NPR-3.

PMID- 20059961
TI  - Gene expression analysis of embryonic photoreceptor precursor cells using BAC-Crx
      EGFP transgenic mouse.
AB  - Crx is a transcription factor which is predominantly expressed in developing and
      mature photoreceptor cells in the retina, and plays a crucial role in the
      terminal differentiation of both rods and cones. Crx is one of the earliest
      expressed genes specifically in photoreceptor precursors, allowing us to trace
      photoreceptor precursor cells from embryonic stages to adult stage by visualizing
      Crx-expressing cells. In the current study, we generated a transgenic mouse line
      which expresses enhanced green fluorescence protein (EGFP) in the retina driven
      by the Crx promoter using bacterial artificial chromosome (BAC) transgenesis.
      EGFP-positive cells were observed in the presumptive photoreceptor layer in the
      retina at embryonic day 15.5 (E15.5), and continued to be expressed in developing
      and mature photoreceptor cells up to adult stage. We sorted EGFP-positive
      photoreceptor precursors at E17.5 using fluorescence-activated cell sorter
      (FACS), and subsequently performed microarray analysis of the FACS-sorted cells.
      We observed various photoreceptor genes, especially cone genes, are enriched in
      the EGFP-positive cells, indicating that embryonic cone photoreceptor precursors
      are enriched. In addition, we found that most of the EGFP-positive cells were
      post-mitotic cells. Thus, the transgenic line we established can serve as a
      useful tool to study both developing and mature photoreceptor cells, including
      embryonic cone precursors whose analysis has been difficult.

PMID- 20059962
TI  - Secreted factor FAM3C (ILEI) is involved in retinal laminar formation.
AB  - FAM3C is a secreted factor, which is involved in the epithelial to mesenchymal
      transition. In transcriptome profiling of the mouse retina using microarray, we
      found that FAM3C is highly expressed in the retina. FAM3C is expressed in the
      ganglion cell layer (GCL) of the retina. To explore the function of FAM3C in
      retinal development, we cloned Xenopus FAM3C (XFAM3C), and performed Xenopus gain
      and loss-of-function analysis. Overexpression of XFAM3C resulted in retinal
      laminar disorganization and an increase in eye size. Loss of function experiments
      of XFAM3C using antisense morpholino oligonucleotides caused photoreceptor cell
      dislocation. Cellular differentiation was not affected by either gain- or loss-of
      function experiments of XFAM3C. These findings suggest that FAM3C is involved in
      retinal laminar formation processes in vertebrates.

PMID- 20059963
TI  - Regulation of interleukin-21 receptor expression and its signal transduction by
      WSB-2.
AB  - Interleukin-21 (IL-21) is a pleiotropic cytokine that regulates T-cell, B-cell,
      NK-cell, and myeloid-cell functions. IL-21 binds with its cognate receptor
      complex, which consists of the IL-21 receptor (IL-21R) and the common gamma chain
      (gammac) receptor subunit. We identified novel IL-21R-binding molecule, WD-40
      repeats containing SOCS-box-2, WSB-2. WSB-2 associated with the membrane-proximal
      intracytoplasmic region of IL-21R, including box1 and box2. Overexpression study
      of WSB-2 showed the reduction of IL-21R expression and IL-21-induced signal
      transduction. On the other hand, small interfering RNA for WSB-2 enhanced the
      expression level of IL-21R and IL-21-induced STAT3 activation, indicating that
      WSB-2 negatively controls the receptor expression. This report provides the first
      evidence that WSB-2 is a regulator of IL-21R expression and IL-21-induced signal
      transduction.

PMID- 20059964
TI  - TGFbeta inducible early gene-1 directly binds to, and represses, the OPG promoter
      in osteoblasts.
AB  - TGFbeta inducible early gene-1 (TIEG) is a member of the Kruppel-like family of
      transcription factors (KLF10) that plays an important role in TGFbeta mediated
      Smad signaling. In order to better understand the role of TIEG in bone, we
      generated TIEG knockout (KO) mice. Calvarial osteoblasts (OBs) isolated from
      these mice exhibit a reduced ability to support osteoclastogenesis in vitro. Gene
      expression studies revealed decreased receptor activator of NF-kappaB ligand
      (RANKL) and increased osteoprotegerin (OPG) expression in TIEG KO OBs, suggesting
      a potential role for TIEG in regulating the expression of these genes. Since OPG
      and RANKL are two important regulators of osteoclast (OC) differentiation, we
      sought to determine if TIEG directly regulates their expression. Luciferase
      constructs, containing fragments of either the mouse OPG promoter (-1486 to +133
      bp) or the RANKL promoter (-2000 to +1 bp) were each cloned into the pGL3 basic
      reporter vector and transiently transfected into TIEG KO calvarial OBs with and
      without a TIEG expression vector. No significant changes in the activity of the
      RANKL promoter were detected in the presence of TIEG. However, OPG promoter
      activity was inhibited in the presence of TIEG protein suggesting that TIEG
      directly represses the expression of OPG in OBs. In order to determine the region
      of this promoter through which TIEG acts, sequential 5'-deletion constructs were
      generated. Transient transfection of these constructs revealed that the TIEG
      regulatory element(s) reside within a 200 bp region of the OPG promoter.
      Transient ChIP analyses, using a TIEG-specific antibody, revealed that TIEG binds
      to this region of the OPG promoter. Since we have previously shown that TIEG
      regulates target gene expression through Sp-1 sites, we examined this region of
      the OPG promoter for potential TIEG binding elements and identified four
      potential Sp-1 binding sites. Site-directed mutagenesis was used to determine if
      TIEG utilizes these Sp-1 elements to regulate the activity of the OPG promoter.
      The data demonstrate that two Sp-1 sites are likely to be involved in TIEG's
      repression of the OPG promoter. Taken together, these results confirm that TIEG
      directly binds to and inhibits OPG promoter activity in OBs, partially explaining
      the inability of TIEG KO OBs to fully support osteoclast differentiation.

PMID- 20059965
TI  - Protein tyrosine phosphatase-1B and T-cell protein tyrosine phosphatase regulate
      IGF-2-induced MCF-7 cell migration.
AB  - The protein tyrosine phosphatase-1B (PTP1B) and the T-cell protein tyrosine
      phosphatase (TC-PTP) have been implicated in down-regulation of tyrosine kinase
      receptors, conferring anti-oncogenic functions to these PTPases. However, recent
      work has shown that PTP1B is positively implicated in oncogenic properties of
      breast cancer cells by regulating the ERK pathway. Here, we studied the function
      of PTP1B and TC-PTP in IGF-2-induced growth, survival and migration of MCF-7
      breast cancer cells. Using siRNA, we showed that reduction in the expression of
      these PTPases decreased cell growth and ERK phosphorylation. Reduction in the
      expression of these PTPases did not impair IGF-2 effects on cell survival to
      acute treatment with 4-OH Tamoxifen. In contrast, IGF-2-induced MCF-7 cell
      migration was markedly impaired by reduction of PTP1B or TC-PTP expression,
      independently of the ERK pathway. This novel finding reinforces the potential
      role of these PTPases as therapeutic targets for treatment of breast cancer.

PMID- 20059966
TI  - Differential distribution of ghrelin-O-acyltransferase (GOAT) immunoreactive
      cells in the mouse and rat gastric oxyntic mucosa.
AB  - The enzyme that acylates ghrelin was recently identified in mice as the fourth
      member of the membrane-bound O-acyltransferases superfamily (MBOAT4) and named
      ghrelin-O-acyltransferase (GOAT). Only one report showed GOAT mRNA expression in
      ghrelin-expressing cells of the mouse stomach. We investigated the distribution
      of GOAT protein in peripheral tissues and co-expression with endocrine markers in
      the gastric mucosa using a custom-made anti-GOAT antibody. Tissues were collected
      from male Sprague-Dawley rats and C57BL/6 mice. Western blot revealed two
      immunoreactive bands in rat and mouse gastric corpus mucosal proteins, a 50 kDa
      band corresponding to the GOAT protein and a 100 kDa band likely corresponding to
      a dimer. Western blot also detected GOAT in the plasma and levels were strongly
      increased after 24-h fasting in mice and slightly in rats. GOAT-immunoreactive
      cells were located in the gastric corpus mucosa and the anterior pituitary gland,
      whereas other peripheral tissues of rats and mice examined were negative. In
      mice, GOAT-immunoreactive cells were mainly distributed throughout the middle
      portion of the oxyntic glands, whereas in rats they were localized mainly in the
      lower portion of the glands. Double labeling showed that 95+/-1% of GOAT
      immunoreactive cells in mice co-labeled with ghrelin, whereas in rats only 56+/
      4% of GOAT-positive cells showed co-expression of ghrelin. The remainder of the
      GOAT-immunopositive cells in rats co-expressed histidine decarboxylase (44+/-3%).
      No co-localization was observed with somatostatin in rats or mice. These data
      suggest species differences between rats and mice in gastric GOAT expression
      perhaps resulting in a different role of the MBOAT4 enzyme in the rat stomach.
      Detection of GOAT in the plasma raises the possibility that ghrelin octanoylation
      may occur in the circulation and the fasting-induced increase in GOAT may
      contribute to the increase of acylated ghrelin after fasting.

PMID- 20059967
TI  - PSF3 marks malignant colon cancer and has a role in cancer cell proliferation.
AB  - PSF3 (partner of Sld five 3) is a member of the tetrameric complex termed GINS,
      composed of SLD5, PSF1, PSF2, and PSF3, and well-conserved evolutionarily.
      Previous studies suggested that some GINS complex members are upregulated in
      cancer, but PSF3 expression in colon carcinoma has not been investigated. Here,
      we established a mouse anti-PSF3 antibody, and examined PSF3 expression in human
      colon carcinoma cell lines and colon carcinoma specimens. We found that PSF3 is
      expressed in the crypt region in normal colonic mucosa and that many PSF3
      positive cells co-expressed Ki-67. This suggests that PSF3-positivity of normal
      mucosa is associated with cell proliferation. Expression of the PSF3 protein was
      greater in carcinoma compared with the adjacent normal mucosa, and even stronger
      in high-grade malignancies, suggesting that it may be associated with colon
      cancer progression. PSF3 gene knock-down in human colon carcinoma cell lines
      resulted in growth inhibition characterized by delayed S-phase progression. These
      results suggest that PSF3 is a potential biomarker for diagnosis of progression
      in colon cancer and could be a new target for cancer therapy.

PMID- 20059968
TI  - Screening of Kozak-motif-located SNPs and analysis of their association with
      human diseases.
AB  - The Kozak motif, which is located near the translational start codon, often
      regulates the protein translation. Moreover, it is believed that the conserved
      positions -3 and +4 contribute the most. Since changes that occur in this motif
      have a great impact on protein yield and in some cases are associated with
      disease, we screened the human SNP database for all Kozak-motif-located SNPs
      (kSNPs) and focused on the strong-changed kSNPs (sckSNPs). Many intron-located
      and synonymous SNPs are reported to be associated with disease, though the
      mechanisms underlying these associations are poorly understood. Here, we
      performed haplotype analysis on sckSNP-containing genes and found that there are
      some sckSNPs that exist in the same haplotype blocks of reported intron-located
      and synonymous disease-associated SNPs, indicating that those kSNPs could be a
      true risk factor for disease-association by affecting the efficiency of protein
      expression. Our findings provide a candidate explanation for how diseases are
      associated with intron-located and synonymous SNPs.

PMID- 20059969
TI  - A poly(dimethylsiloxane)-based device enabling time-lapse imaging with high
      spatial resolution.
AB  - We have developed a regulator-free device that enables long-term incubation of
      mammalian cells for epi-fluorescence imaging, based on a concept that the size of
      sample to be gassed and heated is reduced to observation scale. A
      poly(dimethylsiloxane) block stamped on a coverslip works as a long-lasting
      supplier of CO(2)-rich gas to adjust bicarbonate-containing medium in a tiny
      chamber at physiological pH, and an oil-immersion objective warms cells across
      the coverslip. A time-lapse imaging experiment using HeLa cells stably expressing
      fluorescent cell-cycle indicators showed that the cells in the chamber
      proliferated with normal cell-cycle period over 2 days.

PMID- 20059970
TI  - Metastable primordial germ cell-like state induced from mouse embryonic stem
      cells by Akt activation.
AB  - Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction
      signals during gastrulation. We found that Akt activation during in vitro
      mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing
      spheres with differentiation states between those of ESCs and PGCs. Essential
      regulators for PGC specification and their downstream germ cell-specific genes
      were expressed in the spheres, indicating that the sphere cells had commenced
      differentiation to the germ lineage. However, the spheres did not proceed to
      spermatogenesis after transplantation into testes. Sphere cell transfer to the
      original feeder-free ESC cultures resulted in chaotic differentiation. In
      contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the
      presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was
      observed. These results indicate that Akt signaling promotes a novel metastable
      and pluripotent state that is intermediate to those of ESCs and PGCs.

PMID- 20059971
TI  - Vitellogenin C-terminal fragments participate in fertilization as egg-coat
      binding partners of sperm trypsin-like proteases in the ascidian Halocynthia
      roretzi.
AB  - Sperm trypsin-like proteases are known to play important roles in fertilization,
      but their detailed functions are still unknown. We previously explored the
      binding partners of sperm trypsin-like proteases, HrProacrosin and HrSpermosin,
      in the ascidian Halocynthia roretzi, and we isolated several candidate proteins
      on the vitelline coat. We found that some of these proteins are identical to the
      C-terminal coding region (CT) and von Willebrand factor type D (vWF-D) domain of
      vitellogenin. We also found that CT on the vitelline coat disappears after
      fertilization. Vitellogenin is a large lipid transfer protein that is
      enzymatically processed during vitellogenesis. Although the processed domains
      including phosvitin and lipovitellin are known to function as yolk nutrient
      proteins, the roles of the CT and vWF-D domain remain elusive. Our results showed
      that the CT and vWF-D domain of vitellogenin are processed and attached to the
      vitelline coat, which in turn participate in fertilization as the binding
      partners of sperm proteases.

PMID- 20059972
TI  - Titanium dioxide induces different levels of IL-1beta production dependent on its
      particle characteristics through caspase-1 activation mediated by reactive oxygen
      species and cathepsin B.
AB  - Although titanium dioxide (TiO2) is widely used, its inhalation can induce
      inflammatory diseases accompanied by interleukin-1beta (IL-1beta) production. The
      particle characteristics of TiO2 are important factors in its biological effects.
      It is urgently necessary to investigate the relationship between the particle
      characteristics and biological responses for the development of safe forms of
      TiO2. Here, we systematically compared the production of IL-1beta in response to
      various forms of TiO2 by macrophage-like human THP-1 cells using various sizes
      (nano to micro), crystal structures (anatase or rutile), and shapes (spherical or
      spicular) of TiO2. The production of IL-1beta depended dramatically on the
      characteristics of the TiO2. Notably, smaller anatase and larger rutile particles
      provoked higher IL-1beta production. In addition, IL-1beta production depended on
      active cathepsin B and reactive oxygen species production independent of the
      characteristics of TiO2. Our results provide basic information for the creation
      of safe and effective novel forms of TiO2.

PMID- 20059973
TI  - Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene
      expression.
AB  - The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial
      role in the modulation of diverse metabolic processes in liver. Here, we reported
      the identification of human apolipoprotein A5 (ApoA5), which implicated in
      lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77
      induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of
      human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was
      shown that Nur77 directly regulated human ApoA5 gene expression by binding to a
      Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter
      region. In addition, we demonstrated that blocking of Nur77 transcriptional
      activity via overexpression of dominant negative Nur77 suppressed human ApoA5
      promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken
      together, our results demonstrated that Nur77 is a novel regulator of human ApoA5
      gene expression and provide a new insight into the role of this orphan nuclear
      receptor in lipoprotein metabolism and triglyceride homeostasis.

PMID- 20059974
TI  - StarD4-mediated translocation of 7-hydroperoxycholesterol to isolated
      mitochondria: deleterious effects and implications for steroidogenesis under
      oxidative stress conditions.
AB  - StAR family proteins, including StarD4, play a key role in steroidogenesis by
      transporting cholesterol (Ch) into mitochondria for conversion to pregnenolone.
      Using a model system consisting of peroxidized cholesterol (7 alpha-OOH)
      containing liposomes as donors, we showed that human recombinant StarD4
      accelerates 7 alpha-OOH transfer to isolated liver mitochondria, and to a greater
      extent than Ch transfer. StarD4 had no effect on transfer of non-oxidized or
      peroxidized phosphatidylcholine, consistent with sterol ring specificity. StarD4
      accelerated 7 alpha-OOH transfer to mitochondria resulted in greater
      susceptibility to free radical lipid peroxidation and loss of membrane potential
      than in a non-StarD4 control. The novel implication of these findings is that in
      oxidative stress states, inappropriate StAR-mediated trafficking of peroxidized
      Ch in steroidogenic tissues could result in damage and dysfunction selectively
      targeted to mitochondria.

PMID- 20059975
TI  - Fructated apolipoprotein A-I showed severe structural modification and loss of
      beneficial functions in lipid-free and lipid-bound state with acceleration of
      atherosclerosis and senescence.
AB  - Non-enzymatic glycation of serum apolipoproteins is a main feature of diabetes
      mellitus under hyperglycemia. Advanced glycation end products are implicated in
      the development of aging and metabolic syndrome, including premature
      atherosclerosis in diabetic subjects. ApoA-I is the principal protein constituent
      of HDL. In this study, glycated human apoA-I (gA-I) by fructation was
      characterized on functional and structural correlations in lipid-free and lipid
      bound states. The gA-I showed more spontaneous multimeric band formation up to
      pentamer and exhibited slower elution profile with more degraded fragments from
      fast protein liquid chromatography. The gA-I showed modified secondary structure
      from fluorescence and circular dichroism analysis. Reconstituted high-density
      lipoprotein (rHDL) containing the gA-I had less content of phospholipid with a
      much smaller particle size than those of rHDL-containing nA-I (nA-I-rHDL). The
      rHDL containing gA-I (gA-I-rHDL) consisted of less molecular number of apoA-I
      than nA-I-rHDL with decreased alpha-helical content. Treatment of the gA-I-rHDL
      induced more atherogenic process in macrophage cell and premature senescence in
      human dermal fibroblast cell. Conclusively, fructose-mediated apoA-I glycation
      resulted in severe loss of several beneficial functions of apoA-I and HDL
      regarding anti-senescence and anti-atherosclerosis activities due to a lack of
      anti-oxidant activity with increased susceptibility of protein degradation and
      structural modification.

PMID- 20059976
TI  - The pro-alpha2(XI) collagen gene is expressed in odontoblasts.
AB  - Since the dentine is analogous to bone, its extracellular matrix shares many
      similarities to bone tissues. Similar to the bone, type I collagen is the major
      organic component in dentine. However, little is known about minor fibrillar
      collagens, which seem to be co-expressed such as type I or II collagen. The
      present study examined the gene expression of type V and XI collagens, which play
      important roles in collagen fibril formation and skeletal morphogenesis, using RT
      PCR and in situ hybridization combined with immunohistochemistry. The transcripts
      of pro-alpha1(XI), pro-alpha2(XI), pro-alpha1(V) and pro-alpha2(V) chains were
      present, but not pro-alpha3(V) and pro-alpha1(II) chains, of which an
      overglycosylated variant is pro-alpha3(XI) chain, in mouse incisor tooth, using
      RT-PCR and in situ hybridization. The pro-alpha2(XI) protein, which is mainly
      expressed in cartilage, were observed in the odontoblast using a specific
      polyclonal antibody. Real-time RT-PCR showed that the transcripts of pro
      alpha2(XI), pro-alpha1(V) and pro-alpha2(V) were predominant in crown and that of
      pro-alpha1(XI) in root of the tooth. Finally, the expression of pro-alpha2(XI)
      was confirmed with an odontoblastic cell line transformed with human telomerase
      reverse transcriptase (hTERT) both in vitro and in vivo. The data suggest a new
      subtype of the V/XI collagen molecule containing alpha2(XI) chain.

PMID- 20059977
TI  - Identification and characterization of the activation domain of Ifh1, an
      activator of model TATA-less genes.
AB  - In yeast, TATA box-binding protein TBP can be delivered to protein-coding genes
      by direct interactions with two different coactivators: TFIID, which delivers TBP
      preferentially to TATA-less promoters, and SAGA, which strongly favors TATA box
      containing promoters. Transcriptional activators of SAGA-dependant genes are
      characterized by prototypic acidic activation domains (ADs) that efficiently
      recruit SAGA, but not TFIID, to UAS elements even in the absence of a core
      promoter. In contrast to the well-studied acidic activation domains, little is
      known about the activation domains of activators of TFIID-dependent genes, even
      though these genes constitute more than 80% of eukaryotic protein-coding genes.
      The paradigm for TATA-less genes are the ribosomal protein genes (RPGs). Here we
      have identified the AD of the RPG activator Ifh1p and demonstrate that a minimal
      Ifh1 AD represents a new class of AD that significantly differs from acidic ADs
      in amino acid signature, relative coactivator affinities, and core promoter
      selectivity.

PMID- 20059978
TI  - Specific amino acid residues are involved in substrate discrimination and
      template binding of human REV1 protein.
AB  - REV1 is a member of the Y-family DNA polymerases, but is atypical in utilizing
      only dCTP with a preference for guanine (G) as the template. Crystallography of
      the REV1-DNA-dCTP ternary complex has revealed a unique mechanism by which
      template G is evicted from the DNA helix and incoming dCTP is recognized by an
      arginine residue in an alpha-loop, termed the N-digit. To better understand
      functions of its individual amino acid residues, we made a series of mutant human
      REV1 proteins. We found that R357 and L358 play vital roles in template binding.
      Furthermore, extensive mutation analysis revealed a novel function of R357 for
      substrate discrimination, in addition to previously proposed specific interaction
      with incoming dCTP. We found that the binding pocket for dCTP of REV1 has also
      significant but latent affinity for dGTP. The results suggest that the positive
      charge on R357 could prevent interaction with dGTP. We propose that both direct
      and indirect mechanisms mediated by R357 ensure specificity for dCTP.

PMID- 20059979
TI  - Identification of an anticoagulant peptide that inhibits both fXIa and
      fVIIa/tissue factor from the blood-feeding nematode Ancylostoma caninum.
AB  - Factor VIIa-tissue factor complex (fVIIa/TF) and factor XIa (fXIa) play important
      roles in the initiation and amplification of coagulation, respectively. They may
      be good targets for the development of novel anticoagulants to treat and prevent
      thromboembolic disease. In this study, we cloned, expressed and identified a
      novel anticoagulant peptide, AcaNAP10, from the blood-feeding nematode
      Ancylostoma caninum. AcaNAP10 showed potent anticoagulant activity and doubled
      the activated partial thromboplastin and prothrombin times at estimated
      concentrations of 92.9 nM and 28.8 nM, respectively. AcaNAP10 demonstrated
      distinct mechanisms of action compared with known anticoagulants. It inhibited
      fXIa and fVIIa/TF with IC(50) values of 25.76+/-1.06 nM and 123.9+/-1.71 nM,
      respectively. This is the first report on an anticoagulant that can inhibit both
      fXIa and fVIIa/TF. This anticoagulant peptide may be an alternative molecule for
      the development of novel anticoagulants.

PMID- 20059981
TI  - Selection and validation of reference genes for real-time RT-PCR studies in the
      non-model species Delomys sublineatus, an endemic Brazilian rodent.
AB  - Quantitative real-time RT-PCR (qRT-PCR) is a sensitive technique for gene
      expression analysis. A critical factor for creating reliable data in relative
      quantification is the normalization of the expression data of genes of interest.
      Therefore the needed normalization factor is calculated out of the expression
      data of co-amplified genes that are stable expressed in the certain sample
      material, the so-called reference genes. In this study, we demonstrate the
      important process of validating potential reference genes using a non-model
      species. As there are almost no sequences known of the Pallid Atlantic Forest Rat
      (Delomys sublineatus), a rodent used as indicator species in conservation studies
      of the endangered Brazilian rainforest, suitable primer sets are more problematic
      to find than in model species. Out of nine tested primer sets designed for the
      fully sequenced Mus musculus, five could be used for the establishment of a
      proper running SYBR-Green assay and validation of their constant expression. qRT
      PCR results of 12 cDNAs of Delomys livers were analyzed with three different
      validation software programs: BestKeeper, NormFinder and geNorm. Our approach
      showed that out of the five (Sdha, Canx, Pgk1, Actb and Actg1) potential
      reference genes, the first four should be used for accurate normalization in
      further relative quantification analyses. Transferring data from close-by model
      organisms makes high sensitive real-time RT-PCR applicable even to free-ranging
      non-model organisms. Our approach might be suitable for other non-model
      organisms.

PMID- 20059980
TI  - Genetic immunization based on the ubiquitin-fusion degradation pathway against
      Trypanosoma cruzi.
AB  - Cytotoxic CD8(+) T cells are particularly important to the development of
      protective immunity against the intracellular protozoan parasite, Trypanosoma
      cruzi, the etiological agent of Chagas disease. We have developed a new effective
      strategy of genetic immunization by activating CD8(+) T cells through the
      ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids
      encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD
      pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was
      constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer
      survival period, compared with mice immunized with pASP-2 alone. Depletion of
      CD8(+) T cells abolished protection against T. cruzi in mice immunized with pUB
      ASP-2 while depletion of CD4(+) T cells did not influence the effective immunity.
      Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to
      develop protective immunity induced. These results suggest that ubiquitin-fused
      antigens expressed in antigen-presenting cells were effectively degraded via the
      UFD pathway, and subsequently activated CD8(+) T cells. Consequently,
      immunization with pUB-ASP-2 was able to induce potent protective immunity against
      infection of T. cruzi.

PMID- 20059982
TI  - Water dynamics clue to key residues in protein folding.
AB  - A computational method independent of experimental protein structure information
      is proposed to recognize key residues in protein folding, from the study of
      hydration water dynamics. Based on all-atom molecular dynamics simulation, two
      key residues are recognized with distinct water dynamical behavior in a folding
      process of the Trp-cage protein. The identified key residues are shown to play an
      essential role in both 3D structure and hydrophobic-induced collapse. With
      observations on hydration water dynamics around key residues, a dynamical pathway
      of folding can be interpreted.

PMID- 20059983
TI  - Neuropeptide Y Y1 receptors in the central nucleus of amygdala mediate the
      anxiolytic-like effect of allopregnanolone in mice: Behavioral and
      immunocytochemical evidences.
AB  - Since allopregnanolone (ALLO) elicits anxiolytic-like action and increases
      neuropeptide Y Y1 (NPY Y1) receptors gene expression in the amygdala, we were
      interested in studying the involvement of NPY Y1 receptors in the anxiolytic-like
      actions of ALLO. The anxiety-like behavior was evaluated in mice using Vogel's
      conflict test (VCT), in which number of shocks were measured. ALLO and NPYergic
      agents, alone or in combinations, were administered bilaterally into the central
      nucleus of amygdala (CeA). The intra-CeA administration of ALLO, NPY or NPY Y1/Y5
      receptors agonist [Leu(31), Pro(34)]-NPY resulted in dose-dependent increase in
      the number of shocks in VCT, indicating anxiolytic-like effect. However, opposite
      effect was observed following administration of selective NPY Y1 receptors
      antagonist BIBP3226. While prior administration with NPY or [Leu(31), Pro(34)]
      NPY, at the subeffective dose, potentiated the ALLO-induced anxiolytic-like
      effect, the same was antagonized by BIBP3226. Further, the effect of acute ALLO
      (30 mg/kg, intraperitoneal) on the endogenous NPY system in the CeA, ventral part
      of lateral division of bed nucleus of the stria terminalis (BSTLV), nucleus
      accumbens core (AcbC) and arcuate nucleus (ARC) was studied with
      immunocytochemistry. Acute ALLO treatment significantly decreased the population
      of NPY-immunoreactive cells in the CeA and also in the ARC. While NPY
      immunoreactive fibers were slightly increased in the AcbC and BSTLV, the cells in
      AcbC and fibers in ARC did not respond. We suggest that NPY may mediate ALLO
      induced anxiolytic-like behavior in the neuroanatomical framework of the CeA,
      possibly via NPY Y1 receptors.

PMID- 20059984
TI  - Activation of glutamate transporters in the locus coeruleus paradoxically
      activates descending inhibition in rats.
AB  - Descending noradrenergic inhibition is an important endogenous pain-relief
      mechanism which can be activated by local glutamate signaling. In the present
      study, we examined the effect of glutamate transporter activation by riluzole in
      the regulation of activity of locus coeruleus (LC) neurons, which provide the
      major inhibitory descending noradrenergic projection to the spinal cord. Local
      injection of riluzole into the LC dose-dependently reduced hypersensitivity in
      rats after L5-L6 spinal nerve ligation (SNL). This anti-hypersensitivity effect
      of LC-injected riluzole was blocked by intrathecal administration of the alpha2
      adrenoceptor antagonist idazoxan and intra-LC co-injection of the AMPA antagonist
      6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gap-junction blockers,
      carbenoxolone (CBX) and meclofenamic acid (MEC). In brainstem slices from normal
      rats, riluzole increased phosphorylated cAMP response element binding protein
      (pCREB) expressing nuclei in dopamine-beta-hydroxylase (DbetaH) containing cells
      in the LC. This riluzole-induced pCREB activation in LC neurons was also blocked
      by CNQX and CBX. In the primary astrocyte culture, riluzole enhanced glutamate
      induced glutamate release. Contrary to expectations, these results suggest that
      activation of glutamate transporters in the LC results in increase of
      extracellular glutamate signaling, possibly via facilitation of glutamate release
      from astrocytes, and activation of LC neurons to induce descending inhibition,
      and that this paradoxical action of glutamate transporters in the LC requires gap
      junction connections.

PMID- 20059986
TI  - An early parietal ERP component of the frontoparietal system: EDAN not = N2pc.
AB  - Directing spatial attention or manual response selection by means of arrow cues
      elicits a characteristic sequence of lateralized ERP components. Van Velzen and
      Eimer (2003) proposed that one of these components, the EDAN (early directing
      attention negativity) is not related to the control of spatial attention but is
      instead an N2pc in disguise, related to the visual processing of arrow cues.
      While this proposal seems widely accepted, it has never been evaluated whether
      the hitherto not well-determined scalp distribution of the EDAN matches the well
      established scalp distribution of the N2pc. This paper reviews evidence from
      earlier published work supporting a parietal distribution of the EDAN. This
      strongly argues against the proposed identification with the N2pc. The EDAN may
      instead reflect early parietal activity within the frontoparietal network,
      preceding the frontal activation represented in the anterior directing-attention
      negativity (ADAN).

PMID- 20059985
TI  - Interaction of perinatal and pre-pubertal factors with genetic predisposition in
      the development of neural pathways involved in the regulation of energy
      homeostasis.
AB  - A majority of human obesity is inherited as a polygenic trait. Once obesity
      develops, over 90% of individuals repeatedly regain lost weight after dieting.
      Only surgical interventions offer long lasting weight loss. Thus, clinical data
      suggest that some individuals have a predisposition to develop and maintain an
      elevated body weight set-point once they are provided with sufficient calories to
      gain weight. This set-point is mediated by an integrated neural network that
      controls energy homeostasis. Unfortunately, currently available tools for
      identifying obesity-prone individuals and examining the functioning of these
      neural systems have insufficient resolution to identify specific neural factors
      that cause humans to develop and maintain the obese state. However, rodent models
      of polygenically inherited obesity allow us to investigate the factors that both
      predispose them to become obese and that prevent or enhance the development of
      such obesity. Maternal obesity during gestation and lactation in obesity-prone
      rodents enhances offspring obesity and alters their neural pathways involved in
      energy homeostasis regulation. Early postnatal exposure of obesity-resistant
      offspring to the milk of genetically obese dams alters their hypothalamic
      pathways involved in energy homeostasis causing them to become obese when fed a
      high fat diet as adults. Finally, short-term exercise begun in the early post
      weaning period increases the sensitivity to the anorectic effects of leptin and
      protects obesity-prone offspring from becoming obese for months exercise
      cessation. Such studies suggest that early identification of obesity-prone humans
      and of the factors that can prevent them from becoming obese could provide an
      effective strategy for preventing the world wide epidemic of obesity.

PMID- 20059987
TI  - Differential effects of methamphetamine and SCH23390 on the expression of members
      of IEG families of transcription factors in the rat striatum.
AB  - Methamphetamine (METH) is a psychostimulant that can cause long-lasting
      neurodegenerative effects in humans and animals. These toxic effects appear to
      occur, in part, via activation of dopamine (DA) D1 receptors. This paper assessed
      the possibility that the DA D1 receptor antagonist, SCH23390, might inhibit METH
      induced changes in the expression of several members of immediate early genes
      (IEGs) which are known to control more delayed expression of other genes. We
      found that injections of METH (4x10 mg/kg, given at 2 h intervals) caused
      significant increases in c-fos and fra-2 expression which lasted from 30 min to 4
      h. Pre-treatment with SCH23390, given 30 min before each METH injection,
      completely blocked METH-induced expression of c-fos, but only partially inhibited
      fra-2 mRNA expression. These results were confirmed by Western blot analysis
      which showed METH-induced changes in c-Fos protein expression that were blocked
      by pretreatment with SCH23390. There were also delayed METH-induced DA D1
      receptor-dependent effects on fosB mRNA expression. Even though fra-1 expression
      was not affected by pretreatment with METH alone, the repeated injections of
      SCH23390 caused substantial decreases in fra-1 mRNA expression in both the
      presence and absence of METH. The repeated injections of METH caused no changes
      in the mRNAs for c-jun, junB or junD. However, there were significant increases
      in the phosphorylation of c-Jun protein (ser63). Phosphorylation of c-Jun
      occurred in a delayed fashion (16 and 24 h after the last METH injections) and
      was attenuated by SCH23390 pretreatment. Interestingly, SCH23390 given alone
      caused significant decreases in phospho-c-Jun at all time-points. The METH
      injections also caused delayed induction in the expression of members of the Egr
      family of transcription factors in a DA D1 receptor-dependent fashion. Repeated
      injections of SCH23390 caused substantial suppression of basal striatal egr-1 and
      egr-2 mRNA expression but not of that of egr-3. Both crem and arc mRNA levels
      were induced by METH in a SCH23390-sensitive fashion. Moreover, multiple
      injections of SCH23390 given alone caused marked inhibition of basal arc
      expression. These results show that multiple injections of METH can
      differentially affect the expression of several IEGs, some of which occurred in a
      DA D1 receptor dependent fashion. The SCH23390-mediated suppression of basal fra
      1, egr-1, and egr-2 mRNA levels suggests that their basal expression in the
      striatum might be dependent on tonic stimulation of the DA D1 receptor.

PMID- 20059988
TI  - Altered local coherence in the default mode network due to sevoflurane
      anesthesia.
AB  - Recently we introduced a robust measure, integrated local correlation (ILC), of
      local connectivity in the brain using fMRI data which reflects the temporal
      correlation of brain activity in every voxel neighborhood. The current work
      studies ILC in fMRI data obtained in the absence and presence of sevoflurane
      anesthesia (0%, 2%, and 1% end-tidal concentration, respectively) administered to
      healthy volunteers. ILC was determined specifically in regions of the default
      mode network (DMN) to address local changes in each state. In addition, a
      potential confound in analyses based on correlations due to signal-to-noise
      variations was addressed by wavelet denoising. This accommodated decreases in
      signal power commonly seen during anesthesia without artificially reducing
      derived correlations. Results showed that ILC was significantly reduced in the
      entire DMN during 2% sevoflurane yet recovered in the posterior and anterior
      cingulate cortices as well as inferior parietal cortex during 1% sevoflurane. By
      contrast, ILC remained attenuated prefrontally in the 1% condition, which
      indicates uncoupling of the frontal areas of DMN during light anesthesia. These
      results confirm widespread anesthetic-induced cortical suppression but also
      demonstrate that the local connectivity of the prefrontal cortex is rapidly
      reduced by sevoflurane. It remains to be seen whether these alterations arise
      locally as a direct consequence of anesthetic action on local neurons or are
      driven by distant changes in oscillations and activity elsewhere in the brain.

PMID- 20059989
TI  - Blocking beta2-adrenergic receptor attenuates acute stress-induced amyloid beta
      peptides production.
AB  - Environmental factors play an important role in the Alzheimer's disease (AD)
      development and stress may accelerate the progression of AD. Beta-adrenergic
      receptors are activated by stress and may influence different aspects of
      cognitive function. So, it was hypothesized that stress may accelerate the
      pathological progression of AD by the activation of beta(2)-adrenergic receptor
      (beta(2)-AR). We have investigated the role of acute stress and activation of
      beta(2)-AR in amyloid beta (Abeta) peptides production in a mouse model of acute
      restraint stress. Injections of the beta(2)-AR-selective agonist clenbuterol
      hydrochloride enhanced the production of acute stress-induced Abeta peptides
      production; the beta(2)-AR-selective antagonist ICI 118,551 reduced Abeta
      peptides production. It is suggested that acute stress induces abnormal
      activation of beta(2)-AR which subsequently enhances Abeta peptides (the main
      neuropathological hallmarks of AD) production possibly resulting in the onset of
      AD. The findings indicate that new therapeutic strategies designed to blocking
      beta(2)-AR might be valuable for the prevention and treatment of AD.

PMID- 20059990
TI  - Microglial response to murine leukemia virus-induced encephalopathy is a good
      indicator of neuronal perturbations.
AB  - The neuronal pathology caused by neonatal infection of rats with the PVC-211
      murine leukemia virus (PVC-211 MuLV) and its underlying mechanisms are not well
      defined even though a loss of neurons and spongiform neurodegeneration has been
      reported to accompany the disease. Here we sought to identify sites of
      neurodegeneration using microglial reactivity as an indirect marker and to
      characterize microglial activation during disease progression. Using a panel of
      microglial antibodies including Iba1, OX-42, ED1, and anti-ferritin, we have
      studied the response of microglial cells to neonatal CNS infection with PVC-211
      at post-infection survival times 7, 14, 21, and 28 days. We found that microglial
      activation occurred primarily in the spinal cord and brainstem where it gradually
      increased in intensity over the time course of this study. Other brain areas were
      relatively unremarkable in their microglial reaction to viral infection within
      this time frame. However, the presence of activated microglial cells was not
      correlated directly with the presence of viral glycoprotein (gp70), which was
      expressed in endothelial cells throughout the CNS. Although double-labeling of
      microglia with Iba1 and ED1 revealed numerous actively phagocytic microglia
      during disease progression, not all activated microglia were ED1-positive. In
      addition to the intense microglial activation, we found increased ferritin
      expression sporadically throughout the virus-infected brain. The ferritin
      positive cells were mostly microglia that exhibited dystrophic changes and likely
      represented a degenerating subpopulation of microglial cells. Thus, activated
      microglia can co-exist with degenerating microglia in the same brain region. We
      attempted to localize degenerating neurons or neurites using Fluoro-Jade, anti
      tau, and anti-alpha synuclein staining, but none of these procedures yielded
      results to indicate obvious neuronal pathology. We conclude that the
      visualization of microglial activation is a more sensitive measure of neuronal
      perturbations than direct detection of neuronal pathology which may be subtle and
      not produce overt degenerative changes.

PMID- 20059991
TI  - Comprehensive correlation between neuronal activity and spin-echo blood
      oxygenation level-dependent signals in the rat somatosensory cortex evoked by
      short electrical stimulations at various frequencies and currents.
AB  - It is essential to elucidate the relationship between blood oxygenation level
      dependent (BOLD) signals and neuronal activity for the interpretation of the
      functional magnetic resonance imaging (fMRI) signals; this relationship has been
      quantitatively investigated by animal studies measuring evoked potentials as
      indices of neuronal activity. Although most human fMRI studies employ the event
      related task design, in which the stimulus duration is short, few studies have
      investigated the relationship between BOLD signals and evoked potentials at short
      stimulus durations. The present study investigated this relationship in the
      somatosensory cortex of anesthetized rats by using electrical forepaw stimulation
      at a short duration of 4 s and comprehensively analyzed it at different
      frequencies (1-10 Hz) and currents (0.5-2.0 mA). Somatosensory evoked potential
      (SEP) responses were measured at the scalp using silver ball electrodes. The sum
      of the peak-to-peak amplitude (SigmaSEP) and average SEP (avg. SEP) responses
      were calculated. BOLD signals were obtained using a spin-echo echo-planar imaging
      sequence at 7 T. The relationship between the avg. SEP and BOLD signals varied
      with frequency, whereas that between SigmaSEP and BOLD signals showed a
      significant correlation at varying frequencies and currents. In particular, the
      relationship between SigmaSEP and SigmaBOLD, which is the sum of the BOLD signals
      obtained at each time point reflecting the area under the BOLD response curves,
      mostly converged, irrespective of the frequency. Our results suggest that
      SigmaBOLD obtained using a spin-echo sequence reflects the neural activity as
      quantified by SigmaSEP, which was determined at different frequencies and
      currents.

PMID- 20059992
TI  - Postprandial apolipoprotein B48 is associated with asymptomatic peripheral
      arterial disease: a study in patients with type 2 diabetes and controls.
AB  - BACKGROUND: Postprandial hyperlipidemia is a common feature in type 2 diabetes;
      our aim was to investigate whether there is an association between subclinical
      peripheral arterial disease (PAD) and the levels of apolipoprotein B48, as a
      specific marker for postprandial lipidemia. METHODS: We enrolled 101 patients
      with type 2 diabetes and 73 controls free from clinical cardiovascular disease.
      Main outcome measures were the presence of subclinical PAD, assessed by the ankle
      brachial index, and the intestinal particles measured as the concentration of
      apolipoprotein B48 at fasting and 4h after a mixed breakfast. RESULTS: No control
      had subclinical PAD. Of the 101 diabetic patients, 21 had subclinical PAD. The
      levels of apo B48, both fasting and postprandial, were only significantly raised
      in the diabetic patients who had PAD. The diabetic patients without vascular
      disease had similar concentrations of triglycerides and apo B48 to the controls.
      In binary logistic regression analyses, only smoking and postprandial B48 levels,
      in addition to diabetes, were independently associated with PAD. On the other
      hand, PAD but not diabetes was associated with the fasting and postprandial
      levels of apo B48. CONCLUSION: Our study suggests that apolipoprotein B48 levels
      might be a marker of occult PAD in patients suffering from type 2 diabetes
      mellitus. Accordingly, subclinical PAD should be taken into account in studies on
      postprandial lipidemia involving patients with diabetes.

PMID- 20059993
TI  - Hs2st mediated kidney mesenchyme induction regulates early ureteric bud
      branching.
AB  - Heparan sulfate proteoglycans (HSPGs) are central modulators of developmental
      processes likely through their interaction with growth factors, such as GDNF,
      members of the FGF and TGFbeta superfamilies, EGF receptor ligands and HGF.
      Absence of the biosynthetic enzyme, heparan sulfate 2-O-sulfotransferase (Hs2st)
      leads to kidney agenesis. Using a novel combination of in vivo and in vitro
      approaches, we have reanalyzed the defect in morphogenesis of the Hs2st(-)(/)(-)
      kidney. Utilizing assays that separately model distinct stages of kidney
      branching morphogenesis, we found that the Hs2st(-/-) UB is able to undergo
      branching and induce mesenchymal-to-epithelial transformation when recombined
      with control MM, and the isolated Hs2st null UB is able to undergo branching
      morphogenesis in the presence of exogenous soluble pro-branching growth factors
      when embedded in an extracellular matrix, indicating that the UB is intrinsically
      competent. This is in contrast to the prevailing view that the defect underlying
      the renal agenesis phenotype is due to a primary role for 2-O sulfated HS in UB
      branching. Unexpectedly, the mutant MM was also fully capable of being induced in
      recombination experiments with wild-type tissue. Thus, both the mutant UB and
      mutant MM tissue appear competent in and of themselves, but the combination of
      mutant tissues fails in vivo and, as we show, in organ culture. We hypothesized a
      2OS-dependent defect in the mutual inductive process, which could be on either
      the UB or MM side, since both progenitor tissues express Hs2st. In light of these
      observations, we specifically examined the role of the HS 2-O sulfation
      modification on the morphogenetic capacity of the UB and MM individually. We
      demonstrate that early UB branching morphogenesis is not primarily modulated by
      factors that depend on the HS 2-O sulfate modification; however, factors that
      contribute to MM induction are markedly sensitive to the 2-O sulfation
      modification. These data suggest that key defect in Hs2st null kidneys is the
      inability of MM to undergo induction either through a failure of mutual induction
      or a primary failure of MM morphogenesis. This results in normal UB formation but
      affects either T-shaped UB formation or iterative branching of the T-shaped UB
      (possibly two separate stages in collecting system development dependent upon
      HS). We discuss the possibility that a disruption in the interaction between HS
      and Wnts (e.g. Wnt 9b) may be an important aspect of the observed phenotype. This
      appears to be the first example of a defect in the MM preventing advancement of
      early UB branching past the first bifurcation stage, one of the limiting steps in
      early kidney development.

PMID- 20059994
TI  - Regeneration of oral siphon pigment organs in the ascidian Ciona intestinalis.
AB  - Ascidians have powerful capacities for regeneration but the underlying mechanisms
      are poorly understood. Here we examine oral siphon regeneration in the solitary
      ascidian Ciona intestinalis. Following amputation, the oral siphon rapidly
      reforms oral pigment organs (OPO) at its distal margin prior to slower
      regeneration of proximal siphon parts. The early stages of oral siphon
      reformation include cell proliferation and re-growth of the siphon nerves,
      although the neural complex (adult brain and associated organs) is not required
      for regeneration. Young animals reform OPO more rapidly after amputation than old
      animals indicating that regeneration is age dependent. UV irradiation,
      microcautery, and cultured siphon explant experiments indicate that OPOs are
      replaced as independent units based on local differentiation of progenitor cells
      within the siphon, rather than by cell migration from a distant source in the
      body. The typical pattern of eight OPOs and siphon lobes is restored with
      fidelity after distal amputation of the oral siphon, but as many as 16 OPOs and
      lobes can be reformed following proximal amputation near the siphon base. Thus,
      the pattern of OPO regeneration is determined by cues positioned along the
      proximal distal axis of the oral siphon. A model is presented in which columns of
      siphon tissue along the proximal-distal axis below pre-existing OPO are
      responsible for reproducing the normal OPO pattern during regeneration. This
      study reveals previously unknown principles of oral siphon and OPO regeneration
      that will be important for developing Ciona as a regeneration model in
      urochordates, which may be the closest living relatives of vertebrates.

PMID- 20059995
TI  - NMY-2 maintains cellular asymmetry and cell boundaries, and promotes a SRC
      dependent asymmetric cell division.
AB  - The nonmuscle myosin II NMY-2 is required for cytokinesis as well as for the
      establishment of zygote asymmetry during embryogenesis in Caenorhabditis elegans.
      Here we describe two conditional nmy-2 alleles that rapidly and reversibly
      inactivate the protein. We show that NMY-2 has late-cell-cycle roles in
      maintaining embryonic asymmetries and is also required for a surprisingly late
      step in the maintenance of the cytokinesis furrow. Finally, during a signaling
      induced asymmetric cell division, NMY-2 is required for SRC-dependent
      phosphotyrosine signaling and acts in parallel with WNT-signaling to specify
      endoderm.

PMID- 20059996
TI  - Effects of lipid peroxidation products on lipofuscinogenesis and autophagy in
      human retinal pigment epithelial cells.
AB  - Several lines of evidence suggest that progressive dysfunction of the retinal
      pigment epithelium (RPE) is central to the pathogenesis of age-related macular
      degeneration (AMD). We previously demonstrated that protein modifications with
      lipid peroxidation products, such as 4-hydroxynonenal (HNE) and malondialdehyde
      (MDA), induce lysosomal dysfunction in RPE cells in vitro. Here, we investigated
      whether phagocytosis of modified photoreceptor outer segments (POS) affects
      lipofuscinogenesis and autophagy, two interrelated processes directly connected
      to lysosomal function. Incubation of human RPE cells with HNE- and MDA-modified
      POS resulted in pronounced intracellular accumulation of granular material with
      lipofuscin-like autofluorescence. After daily treatment with modified POS for 7
      days, cellular autofluorescence increased 8.2-fold as quantified by flow
      cytometry. In the presence of the lysosomal inhibitor ammonium chloride,
      unmodified POS likewise induced an 8.0-fold increase in autofluorescence.
      Spectral profiles of cellular autofluorescence after incubation with modified POS
      were unchanged compared to incubation with native POS. Autophagy activity,
      measured as turnover of metabolically radiolabeled endogenous proteins, was
      reduced by both HNE- and MDA-modified POS by 40%. Autophagy inhibition by 3
      methyladenine and lysosomal inhibition by ammonium chloride induced
      lipofuscinogenesis even in the absence of POS. In summary, our results
      demonstrate that induction of lysosomal dysfunction by lipid peroxidation-derived
      protein modifications results in increased lipofuscinogenesis and reduced
      autophagy activity in RPE cells in vitro. These mechanisms may contribute to RPE
      cell dysfunction and degeneration in AMD.

PMID- 20059997
TI  - Somatotopic organization in the internal segment of the globus pallidus in
      Parkinson's disease.
AB  - Ablation or deep brain stimulation in the internal segment of the globus pallidus
      (GPi) is an effective therapy for the treatment of Parkinson's disease (PD). Yet
      many patients receive only partial benefit, including varying levels of
      improvement across different body regions, which may relate to a differential
      effect of GPi surgery on the different body regions. Unfortunately, our
      understanding of the somatotopic organization of human GPi is based on a small
      number of studies with limited sample sizes, including several based upon only a
      single recording track or plane. To fully address the three-dimensional
      somatotopic organization of GPi, we examined the receptive field properties of
      pallidal neurons in a large cohort of patients undergoing stereotactic surgery.
      The response of neurons to active and passive movements of the limbs and
      orofacial structures was determined, using a minimum of three tracks across at
      least two medial-lateral planes. Neurons (3183) were evaluated from 299 patients,
      of which 1972 (62%) were modulated by sensorimotor manipulation. Of these, 1767
      responded to a single, contralateral body region, with the remaining 205
      responding to multiple and/or ipsilateral body regions. Leg-related neurons were
      found dorsal, medial and anterior to arm-related neurons, while arm-related
      neurons were dorsal and lateral to orofacial-related neurons. This study provides
      a more detailed map of individual body regions as well as specific joints within
      each region and provides a potential explanation for the differential effect of
      lesions or DBS of the GPi on different body parts in patients undergoing surgical
      treatment of movement disorders.

PMID- 20059999
TI  - Transplantable midbrain dopamine neurons: a moving target.

PMID- 20059998
TI  - Functional electrical stimulation helps replenish progenitor cells in the injured
      spinal cord of adult rats.
AB  - Functional electrical stimulation (FES) can restore control and offset atrophy to
      muscles after neurological injury. However, FES has not been considered as a
      method for enhancing CNS regeneration. This paper demonstrates that FES
      dramatically enhanced progenitor cell birth in the spinal cord of rats with a
      chronic spinal cord injury (SCI). A complete SCI at thoracic level 8/9 was
      performed on 12 rats. Three weeks later, a FES device to stimulate hindlimb
      movement was implanted into these rats. Twelve identically-injured rats received
      inactive FES implants. An additional control group of uninjured rats were also
      examined. Ten days after FES implantation, dividing cells were marked with
      bromodeoxyuridine (BrdU). The "cell birth" subgroup (half the animals in each
      group) was sacrificed immediately after completion of BrdU administration, and
      the "cell survival" subgroup was sacrificed 7 days later. In the injured "cell
      birth" subgroup, FES induced an 82-86% increase in cell birth in the lumbar
      spinal cord. In the injured "cell survival" subgroup, the increased lumbar
      newborn cell counts persisted. FES doubled the proportion of the newly-born cells
      which expressed nestin and other markers suggestive of tripotential progenitors.
      In uninjured rats, FES had no effect on cell birth/survival. This report suggests
      that controlled electrical activation of the CNS may enhance spontaneous
      regeneration after neurological injuries.

PMID- 20060000
TI  - In utero cortisol and testosterone exposure and fear reactivity in infancy.
AB  - Fetal programming is emerging as a major conceptual model for understanding
      developmental origins of health and disease, including behavioral outcomes. As
      part of a larger study of prenatal stress and child development, we examined the
      association between prenatal hormone exposure and fear reactivity, a temperament
      dimension that is a predictor of long-term behavioral adjustment. Amniotic fluid
      was collected from a sample of women undergoing clinically indicated
      amniocentesis for later analysis of cortisol and testosterone. Children with
      normal birth outcomes were recalled for follow-up assessment at 17 months, at
      which time we administered an observational assessment of temperament (lab-TAB;
      n=108). Information on pregnancy and obstetric outcome was included as
      covariates. Results indicated that there was a significant association between
      prenatal testosterone and observed fear reactivity in boys (r(53)=0.34, p=0.01);
      no significant effect was found in girls (r(54)=-0.07, ns); the effect remained
      when obstetric, psychosocial, and parental anxiety were controlled for. There was
      not a significant association between fetal cortisol exposure and fear
      reactivity. The prediction from in utero testosterone exposure to fear reactivity
      in boys extends prior research on prenatal testosterone and may represent an
      association with a general predisposition to greater arousal and reactivity.

PMID- 20060002
TI  - Kinetics of cardiac sarcomeric processes and rate-limiting steps in contraction
      and relaxation.
AB  - The sarcomere is the core structure responsible for active mechanical heart
      function. It is formed primarily by myosin, actin, and titin filaments. Cyclic
      interactions occur between the cross-bridges of the myosin filaments and the
      actin filaments. The forces generated by these cyclic interactions provide the
      molecular basis for cardiac pressure, while the motion produced by these
      interactions provides the basis for ejection. The cross-bridge cycle is
      controlled by upstream mechanisms located in the membrane and by downstream
      mechanisms inside the sarcomere itself. These downstream mechanisms involve the
      Ca(2+)-controlled conformational change of the regulatory proteins troponin and
      tropomyosin and strong cooperative interactions between neighboring troponin
      tropomyosin units along the actin filament. The kinetics of upstream and
      downstream processes have been measured in intact and demembranated myocardial
      preparations. This review outlines a conceptual model of the timing of these
      processes during the individual mechanical heart phases. Particular focus is
      given to kinetic data from studies on contraction-relaxation cycles under
      mechanical loads. Evidence is discussed that the dynamics of cardiac contraction
      and relaxation are determined mainly by sarcomeric downstream mechanisms, in
      particular by the kinetics of the cross-bridge cycle. The rate and extent of
      ventricular pressure development is essentially subjected to the mechanistic
      principles of cross-bridge action and its upstream and downstream regulation.
      Sarcomere relengthening during myocardial relaxation plays a key role in the
      rapid decay of ventricular pressure and in early diastolic filling.

PMID- 20060001
TI  - Delayed enrichment of mesenchymal cells promotes cardiac lineage and calcium
      transient development.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) can be induced to
      differentiate into myogenic cells. Despite their potential, previous studies have
      not been successful in producing a high percentage of cardiac-like cells with a
      muscle phenotype. We hypothesized that cardiac lineage development in BM-MSC is
      related to cell passage, culture milieu, and enrichment for specific cell
      subtypes before and during differentiation. Our study demonstrated that Lin(-) BM
      MSC at an intermediate passage (IP; P8-P12) expressed cardiac troponin T (cTnT)
      after 21 days in culture. Cardiac TnT expression was similar whether IP cells
      were differentiated in media containing 5-azacytidine+2% FBS (AZA; 14%) or 2% FBS
      alone (LS; 12%) and both were significantly higher than AZA+5% FBS. This
      expression was potentiated by first enriching for CD117/Sca-1 cells followed by
      differentiation (AZA, 39% and LS, 28%). A second sequential enrichment for the
      dihydropyridine receptor subunit alpha2delta1 (DHPR-alpha2) resulted in cardiac
      TnT expressed in 54% of cultured cells compared to 28% of cells after CD117/Sca
      1(+) enrichment. Cells enriched for CD117/Sca-1 and subjected to differentiation
      displayed spontaneous intracellular Ca(2+) transients with an increase in
      transient frequency and a 60% decrease in the transient duration amplitude
      between days 14 and 29. In conclusion, IP CD117/Sca-1(+) murine BM-MSCs display
      robust cardiac muscle lineage development that can be induced independent of AZA
      but is diminished under higher serum concentrations. Furthermore, temporal
      changes in calcium kinetics commensurate with increased cTnT expression suggest
      progressive maturation of a cardiac muscle lineage. Enrichment with CD117/Sca-1
      to establish lineage commitment followed by DHPR-alpha2 in lineage developing
      cells may enhance the therapeutic potential of these cells for transplantation.

PMID- 20060003
TI  - Cellular repressor of E1A-stimulated genes inhibits human vascular smooth muscle
      cell apoptosis via blocking P38/JNK MAP kinase activation.
AB  - Vascular smooth muscle cell (VSMC) apoptosis accelerates atherosclerosis and
      promotes restenosis following vascular injury. The current study examined the
      effects of cellular repressor of E1A-stimulated genes (CREG), a novel
      glycoprotein inhibiting transcription activation, on the regulation of VSMC
      apoptosis. Serum starvation or treatment of human VSMCs with apoptosis inducers
      (STS or VP-16) significantly reduced CREG expression and caused caspase-3
      activation. CREG downregulation and caspase-3 activation were inversely related,
      suggesting that reduced CREG expression may contribute to VSMC apoptosis. Both
      loss-of-function (CREG-DW produced by retroviruses expressing CREG shRNAs) and
      gain-of-function (CREG-UP produced by retroviral infection with vector pLNCX
      CREG) studies were performed to confirm this hypothesis. CREG-DW significantly
      increased VSMC apoptosis, whereas CREG-UP significantly reduced apoptosis.
      Moreover, p38 and JNK mitogen-activated protein kinases were significantly
      upregulated in CREG-DW and significantly reduced in CREG-UP VSMCs. More
      importantly, CREG-DW-induced VSMC apoptosis was blocked by the p38-specific
      inhibitor SB203580 or by overexpression of a dominant-negative P38 alpha (p38
      alpha AGF). Balloon injury-induced vascular caspase-3 activation was
      significantly inhibited by treatment with recombinant CREG protein. These results
      demonstrated for the first time that CREG plays a key role in modulating VSMC
      apoptosis through the p38 and JNK signal transduction pathways, both in vitro and
      in situ.

PMID- 20060004
TI  - The signalling pathway of CaMKII-mediated apoptosis and necrosis in the
      ischemia/reperfusion injury.
AB  - Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) plays an important role
      mediating apoptosis/necrosis during ischemia-reperfusion (IR). We explored the
      mechanisms of this deleterious effect. Langendorff perfused rat and transgenic
      mice hearts with CaMKII inhibition targeted to sarcoplasmic reticulum (SR-AIP)
      were subjected to global IR. The onset of reperfusion increased the
      phosphorylation of Thr(17) site of phospholamban, without changes in total
      protein, consistent with an increase in CaMKII activity. Instead, there was a
      proportional decrease in the phosphorylation of Ser2815 site of ryanodine
      receptors (RyR2) and the amount of RyR2 at the onset of reperfusion, i.e. the
      ratio Ser2815/RyR2 did not change. Inhibition of the reverse
      Na(+)/Ca(2+)exchanger (NCX) mode (KBR7943) diminished phospholamban
      phosphorylation, reduced apoptosis/necrosis and enhanced mechanical recovery.
      CaMKII-inhibition (KN-93), significantly decreased phospholamban phosphorylation,
      infarct area, lactate dehydrogenase release (LDH) (necrosis), TUNEL positive
      nuclei, caspase-3 activity, Bax/Bcl-2 ratio and Ca(2+)-induced mitochondrial
      swelling (apoptosis), and increased contractile recovery when compared with non
      treated IR hearts or IR hearts pretreated with the inactive analog, KN-92.
      Blocking SR Ca(2+) loading and release (thapsigargin/dantrolene), mitochondrial
      Ca(2+) uniporter (ruthenium red/RU360), or mitochondrial permeability transition
      pore (cyclosporine A), significantly decreased infarct size, LDH release and
      apoptosis. SR-AIP hearts failed to show an increase in the phosphorylation of
      Thr(17) of phospholamban at the onset of reflow and exhibited a significant
      decrease in infarct size, apoptosis and necrosis respect to controls. The results
      reveal an apoptotic-necrotic pathway mediated by CaMKII-dependent
      phosphorylations at the SR, which involves the reverse NCX mode and the
      mitochondria as trigger and end effectors, respectively, of the cascade.

PMID- 20060005
TI  - The limiting conditional probability distribution in a stochastic model of T cell
      repertoire maintenance.
AB  - The limiting conditional probability distribution (LCD) has been much studied in
      the field of mathematical biology, particularly in the context of epidemiology
      and the persistence of epidemics. However, it has not yet been applied to the
      immune system. One of the characteristic features of the T cell repertoire is its
      diversity. This diversity declines in old age, whence the concepts of extinction
      and persistence are also relevant to the immune system. In this paper we model T
      cell repertoire maintenance by means of a continuous-time birth and death process
      on the positive integers, where the origin is an absorbing state. We show that
      eventual extinction is guaranteed. The late-time behaviour of the process before
      extinction takes place is modelled by the LCD, which we prove always exists for
      the process studied here. In most cases, analytic expressions for the LCD cannot
      be computed but the probability distribution may be approximated by means of the
      stationary probability distributions of two related processes. We show how these
      approximations are related to the LCD of the original process and use them to
      study the LCD in two special cases. We also make use of the large N expansion to
      derive a further approximation to the LCD. The accuracy of the various
      approximations is then analysed.

PMID- 20060006
TI  - Blood-brain barrier permeability and tPA-mediated neurotoxicity.
AB  - Tissue type plasminogen activator (tPA) can induce neuronal apoptosis, disrupt
      the blood-brain barrier (BBB), and promote dilation of the cerebral vasculature.
      The timing, sequence and contributions of these and other deleterious effects of
      tPA and their contribution to post-ischemic brain damage after stroke, have not
      been fully elucidated. To dissociate the effects of tPA on BBB permeability,
      cerebral vasodilation and protease-dependent pathways, we developed several tPA
      mutants and PAI-1 derived peptides constructed by computerized homology modeling
      of tPA. Our data show that intravenous administration of human tPA to rats
      increases BBB permeability through a non-catalytic process that is associated
      with reversible neurotoxicity, brain damage, mortality and contributes
      significantly to its brief therapeutic window. Furthermore, our data show that
      inhibiting the effect of tPA on BBB function without affecting its catalytic
      activity, improves outcome and significantly extends its therapeutic window in
      mechanical as well as in thromboembolic models of stroke.

PMID- 20060008
TI  - High-intensity sweeteners and energy balance.
AB  - Recent epidemiological evidence points to a link between a variety of negative
      health outcomes (e.g. metabolic syndrome, diabetes and cardiovascular disease)
      and the consumption of both calorically sweetened beverages and beverages
      sweetened with high-intensity, non-caloric sweeteners. Research on the
      possibility that non-nutritive sweeteners promote food intake, body weight gain,
      and metabolic disorders has been hindered by the lack of a physiologically
      relevant model that describes the mechanistic basis for these outcomes. We have
      suggested that based on Pavlovian conditioning principles, consumption of non
      nutritive sweeteners could result in sweet tastes no longer serving as consistent
      predictors of nutritive postingestive consequences. This dissociation between the
      sweet taste cues and the caloric consequences could lead to a decrease in the
      ability of sweet tastes to evoke physiological responses that serve to regulate
      energy balance. Using a rodent model, we have found that intake of foods or
      fluids containing non-nutritive sweeteners was accompanied by increased food
      intake, body weight gain, accumulation of body fat, and weaker caloric
      compensation, compared to consumption of foods and fluids containing glucose. Our
      research also provided evidence consistent with the hypothesis that these effects
      of consuming saccharin may be associated with a decrement in the ability of sweet
      taste to evoke thermic responses, and perhaps other physiological, cephalic
      phase, reflexes that are thought to help maintain energy balance.

PMID- 20060009
TI  - Light responses of the circadian system in leptin deficient mice.
AB  - Some evidences postulate a link between obesity and disturbances in circadian
      behavior. Here, we studied the manifestation of the circadian rhythm of motor
      activity and its response to light in the leptin deficiency model of obesity
      ob/ob mice. Motor activity in both ob/ob and wild type mice was first recorded in
      a small cage by activity meters with crossed infrared beams (IR) and later in a
      larger cage with a running wheel, where the number of wheel revolutions (WR) was
      also determined. Animals were maintained under light-dark (LD) or constant-dark
      (DD) conditions. We studied the free-running period and the rhythm profile, with
      special emphasis on the amount of activity in the dark and light phases of the LD
      cycle, and the phase and period responses to a light pulse. The results showed
      that ob/ob mice have a strong ultradian, rather than a circadian pattern, whose
      period range between 3 and 4.8h. Also, these animals showed a percentage of
      activity during light higher than controls. We did not find differences in the
      endogenous period of the circadian rhythm between mice groups in DD. However,
      ob/ob mice showed stronger phase delays after a light pulse at ZT15 than
      controls, and less masking effects in the transition from LD to DD compared with
      controls. This suggests a weaker circadian pacemaker of the ob/ob mice compared
      with controls.

PMID- 20060007
TI  - Hippocampal neurogenesis as a target for the treatment of mental illness: a
      critical evaluation.
AB  - Over one-quarter of adult Americans are diagnosed with a mental illness like
      Major Depressive Disorder (MDD), Post-Traumatic Stress Disorder (PTSD),
      schizophrenia, and Alzheimer's Disease. In addition to the exceptional personal
      burden these disorders exert on patients and their families, they also have
      enormous cost to society. Although existing pharmacological and psychosocial
      treatments alleviate symptoms in many patients, the comorbidity, severity, and
      intractable nature of mental disorders strongly underscore the need for novel
      strategies. As the hippocampus is a site of structural and functional pathology
      in most mental illnesses, a hippocampal-based treatment approach has been
      proposed to counteract the cognitive deficits and mood dysregulation that are
      hallmarks of psychiatric disorders. In particular, preclinical and clinical
      research suggests that hippocampal neurogenesis, the generation of new neurons in
      the adult dentate gyrus, may be harnessed to treat mental illness. There are
      obvious applications and allures of this approach; for example, perhaps
      stimulating hippocampal neurogenesis would reverse the overt and noncontroversial
      hippocampal atrophy and functional deficits observed in Alzheimer's Disease and
      schizophrenia, or the more controversial hippocampal deficits seen in MDD and
      PTSD. However, critical examination suggests that neurogenesis may only correlate
      with mental illness and treatment, suggesting targeting neurogenesis alone is not
      a sufficient treatment strategy. Here we review the classic and causative links
      between adult hippocampal neurogenesis and mental disorders, and provide a
      critical evaluation of how (and if) our basic knowledge of new neurons in the
      adult hippocampus might eventually help combat or even prevent mental illness.

PMID- 20060010
TI  - Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a
      possible pathway through the induction of heme oxygenase-1 expression.
AB  - Puerarin is a natural product isolated from Puerarin lobata and has various
      pharmacological effects, including anti-hyperglycemic and anti-allergic
      properties. In the present study, we investigated the effect of puerarin against
      advanced glycation end products (AGEs)-induced inflammation in mouse mesangial
      cells. Puerarin acts by inducing the expression of heme oxygenase-1 (HO-1) in a
      dose- and time-dependent manner. Puerarin was able to enhance phosphorylation of
      protein kinase C (PKC) delta, but not PKC alpha/beta II, in a time-dependent
      manner. Induction of HO-1 expression by puerarin was suppressed by GF109203X, a
      general inhibitor of PKC, and by rottlerin, a specific inhibitor of PKC delta.
      However, induction was not suppressed by Go6976, a selective inhibitor for PKC
      alpha/beta II. Additionally, the knockdown of endogenous PKC delta by small
      interfering RNA (siRNA) resulted in the inhibition of HO-1 expression and Akt
      phosphorylation. Puerarin increased antioxidant response element (ARE)-Luciferase
      activity in a dose- and time-dependent manner in transfected mouse mesangial
      cells. Mutation of the ARE sequence abolished puerarin-induced HO-1 expression.
      Furthermore, puerarin treatments resulted in a marked increase in NF-E2 related
      factor-2 (Nrf-2) translocation, leading to up-regulation of HO-1 expression.
      However, transfection of Nrf-2 specific siRNA abolished HO-1 expression.
      Pretreatment with puerarin inhibited the expressions of COX-2, MMP-2 and MMP-9.
      But, these effects were reversed by ZnPP, an inhibitor of HO-1. Taken together,
      our results demonstrate that puerarin-induced expression of HO-1 is mediated by
      the PKC delta-Nrf-2-HO-1 pathway and inhibits N-carboxymethyllysine (CML)-induced
      inflammation in mouse mesangial cells.

PMID- 20060012
TI  - Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial
      fibroblasts.
AB  - Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of
      Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to
      altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic
      nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for
      inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were
      examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular
      mitogenesis rather than cell death by either necrosis or apoptosis. There were no
      changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein
      expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde
      treatments in these cells. HG-induced extracellular signal-regulated kinase
      (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)
      (but not the Janus kinase 2/signal transducers and activators of transcription)
      activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde
      to inhibit HG-induced hypertrophy was verified by the observation that it
      significantly decreased cell size, cellular hypertrophy index, and protein levels
      of collagen IV, fibronectin, and alpha-smooth muscle actin (alpha-SMA). The
      results obtained in this study suggest that cinnamaldehyde treatment of renal
      interstitial fibroblasts that have been stimulated by HG reduces their ability to
      proliferate and hypertrophy through mechanisms that may be dependent on
      inactivation of the ERK/JNK/p38 MAPK pathway.

PMID- 20060013
TI  - Immunome and venome of Bothrops jararacussu: a proteomic approach to study the
      molecular immunology of snake toxins.
AB  - A combination of anti-bothropic and anti-crotalic sera has been reported to be
      more effective in neutralizing the effects of Bothrops jararacussu venom than
      anti-bothropic serum alone. The role of proteins from B. jararacussu venom in the
      horse immune response was evaluated via the analysis of cross-reactivity with
      homologous and heterologous sera. Many of the proteins in B. jararacussu venom
      were identified via 2D gel electrophoresis. Western blots revealed that anti
      jararacussu showed higher reactivity to l-aminoxidase (LAOs) and snake venom
      metalloproteinase, (SVMPs) and weaker reactivity towards Snake venom serine
      proteases (SVSPs), PLA(2), C-type lectin and cysteine-rich proteins. Anti
      jararaca preferentially recognized LAOs, SVMPs and SVSPs. Both of these sera
      failed to recognize low-molecular weight proteins. Anti-crotalic serum clearly
      recognized LAOs, C-type lectin, SVSP, cysteine-rich proteins, SVMP and Asp49
      PLA(2). The cross-reactivity with anti-PLA(2) revealed the immunoreactivity of
      these antibodies to proteins with molecular masses in a range that is poorly
      recognized by other studied anti-sera. Our results suggest that the contribution
      of anti-crotalic serum to the neutralization of B. jararacussu by may be due to
      its cross-reactivity with proteins such as C-type lectins, SVSPs, Asp49-PLA(2).
      These results also reinforce the importance of neutralizing the highly toxic
      proteins inclusive those with low immunogenicity in commercial antivenom
      production to obtain a highly protective serum against snake venoms.

PMID- 20060011
TI  - Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of
      trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2).
AB  - N-acetyl-S-(1,2-dichlorovinyl)-l-cysteine (Ac-DCVC) and S-(1,2-dichlorovinyl)-l
      cysteine (DCVC) are the glutathione conjugation pathway metabolites of a common
      industrial contaminant and potent nephrotoxicant trichloroethylene (TCE). Ac-DCVC
      and DCVC are accumulated in the renal proximal tubule where they may be secreted
      into the urine by an unknown apical transporter(s). In this study, we explored
      the hypothesis that the apical transport of Ac-DCVC and/or DCVC may be mediated
      by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to
      mediate proximal tubular apical ATP-dependent transport of glutathione and
      numerous xenobiotics and endogenous substances conjugated with glutathione.
      Transport experiments using membrane vesicles prepared from mouse proximal tubule
      derived cells expressing mouse Mrp2 utilizing ATPase assay and direct
      measurements of Ac-DCVC/DCVC using liquid chromatography/tandem mass-spectrometry
      (LC/MS/MS) demonstrated that mouse Mrp2 mediates ATP-dependent transport of Ac
      DCVC. Expression of mouse Mrp2 antisense mRNA significantly inhibited the
      vectorial basolateral to apical transport of Ac-DCVC but not DCVC in mouse
      proximal tubule derived cells endogenously expressing mouse Mrp2. The results
      suggest that Mrp2 may be involved in the renal secretion of Ac-DCVC.

PMID- 20060014
TI  - Phomenins and fatty acids from Alternaria infectoria.
AB  - Taxa of the Alternaria infectoria species group are the predominant Alternaria
      spp. found in cereals in Northern Europe. While several pyrones have been
      isolated from A. infectoria and described as taxonomical markers for species
      identification, information about the bioactivity of metabolites from the fungus
      is missing. Bioassay-guided fractionation of rice culture extracts from several
      strains of A. infectoria linked the observed toxicity of the extracts in MRC-5
      cells to free fatty acids, i.e. linoleic acid and alpha-linolenic acid. The
      fungus also produced a cytotoxic pyrone, which upon isolation and NMR
      spectroscopic analysis was identified as a mixture of phomenins A and B
      (approximately 10:1), which have not previously been isolated from an Alternaria
      species.

PMID- 20060016
TI  - Dogs turn left to emotional stimuli.
AB  - During feeding behaviour, dogs were suddenly presented with 2D stimuli depicting
      the silhouette of a dog, a cat or a snake simultaneously into the left and right
      visual hemifields. A bias to turn the head towards the left rather than the right
      side was observed with the cat and snake stimulus but not with the dog stimulus.
      Latencies to react following stimulus presentation were lower for left than for
      right head turning, whereas times needed to resume feeding behaviour were higher
      after left rather than after right head turning. When stimuli were presented only
      to the left or right visual hemifields, dogs proved to be more responsive to left
      side presentation, irrespective of the type of stimulus. However, cat and snake
      stimuli produced shorter latencies to react and longer times to resume feeding
      following left rather than right monocular visual hemifield presentation. Results
      demonstrate striking lateralization in dogs, with the right side of the brain
      more responsive to threatening and alarming stimuli. Possible implications for
      animal welfare are discussed.

PMID- 20060015
TI  - Functional role of gamma and theta oscillations in episodic memory.
AB  - The primary aim of this review is to examine evidence for a functional role of
      gamma and theta oscillations in human episodic memory. It is proposed here that
      gamma and theta oscillations allow for the transient interaction between cortical
      structures and the hippocampus for the encoding and retrieval of episodic
      memories as described by the hippocampal memory indexing theory (Teyler and
      DiScenna, 1986). Gamma rhythms can act in the cortex to bind perceptual features
      and in the hippocampus to bind the rich perceptual and contextual information
      from diverse brain regions into episodic representations. Theta oscillations act
      to temporally order these individual episodic memory representations. Through
      feedback projections from the hippocampus to the cortex these gamma and theta
      patterns could cause the reinstatement of the entire episodic memory
      representation in the cortex. In addition, theta oscillations could allow for top
      down control from the frontal cortex to the hippocampus modulating the encoding
      and retrieval of episodic memories.

PMID- 20060017
TI  - Effects of photoperiod and experience on aggressive behavior in female California
      mice.
AB  - Aggressive behavior among females is observed in many species, but the mechanisms
      of this behavior have historically been understudied. In many species of rodents,
      winter-like short day photoperiods induce increased aggression levels compared to
      summer-like long day photoperiods. Recent reports in hamsters show that short
      days also increase aggression in females. We examined the effects of photoperiod
      on aggression in female California mice, and for the first time compare brain
      activity of aggression-tested female rodents under different photoperiods. We
      observed that female California mice were more aggressive when housed in short
      days versus long days. Intriguingly, we also observed that under long days female
      attack latency decreases with repeated testing in resident-intruder tests. These
      data suggest that winner effects that have been described in males may also occur
      in females. We also used the expression of phosphorylated extracellular signal
      regulated kinases (pERK) in the brain to estimate brain activity during
      aggression tests. pERK can alter neuronal activity in the short term and in the
      long term can act as a transcription factor. Using immunoblot analyses we
      observed that aggression-induced pERK expression in the female bed nucleus of the
      stria terminalis and medial amygdala occurs under both long and short days. Thus,
      the mechanisms controlling increased aggression under short days are still
      unclear and additional study is needed.

PMID- 20060018
TI  - The history of the cholinergic hypothesis.
AB  - The cholinergic hypothesis of cognitive impairment and Alzheimer's disease has
      been for decades a "polar star" for studies on dementia and neurodegenerative
      diseases. Aim of the present article is to briefly summarize its birth and its
      evolution throughout years and discoveries. Putting the cholinergic hypothesis in
      an historical perspective, allows to appreciate the enormous amount of
      experimental and clinical research that it has stimulated over years and the
      impressive extent of knowledge generated by this research. While some of the
      assumptions at the basis of its original formulation are disputable in the light
      of recent developments, the cholinergic hypothesis has, however, constituted an
      invaluable stimulus to better understand not only the anatomy and the
      biochemistry of the cholinergic systems of brain connections but also its
      developmental biology, its complex relationships with trophic factors, its role
      in cognitive functions. Thus, rather than being consigned to history, the
      cholinergic hypothesis will likely contribute to further understanding dementia
      and neurodegenerative diseases and will hopefully be integrated in novel
      therapies and treatments.

PMID- 20060019
TI  - Developmental aspects of the cholinergic system.
AB  - Beyond its importance in sustaining or modulating different aspects of the
      activity of the central nervous system (CNS), the cholinergic system plays
      important roles during development. In the current review, we focus on the
      developmental aspects associated with major components of the cholinergic system:
      Acetylcholine, choline acetyltransferase, vesicular acetylcholine transporter,
      high-affinity choline transporter, acetylcholinesterase, nicotinic and muscarinic
      receptors. We describe when and where each one of these components is first
      identified in the CNS and the changes in their levels that occur during the
      course of prenatal and postnatal development. We also describe how these
      components are relevant to many events that occur during the development of the
      CNS, including progenitor cells proliferation and differentiation, neurogenesis,
      gliogenesis, neuronal maturation and plasticity, axonal pathfinding, regulation
      of gene expression and cell survival. It will be noticed that evidence regarding
      the developmental aspects of the cholinergic system comes mostly from studies
      that used agonists, such as nicotine, and antagonists, such as hemicholinium-3.
      Studies using immunohistochemistry and genetically altered mice also provided
      valuable information.

PMID- 20060020
TI  - One-trial object recognition in rats and mice: methodological and theoretical
      issues.
AB  - The one-trial object recognition task involves memory of a familiar object in
      parallel with the detection and encoding of a novel object. It provides the basis
      for the study of a wide range of cognitive and neuropsychological functions and
      processes in rats and mice. However, unlike in humans, primate and pigeon
      studies, object recognition in rats and mice has been mostly limited to memory
      while little is known about object perception, affordances and acquisition of a
      representation of an object. In the present paper, we addressed some of these
      issues. We also described novelty preference models and hypotheses that account
      for one-trial object recognition and question the validity of the novelty
      preference concept. In addition, we discussed whether one-trial object
      recognition involves working memory and how it involves memory of an episode.

PMID- 20060021
TI  - The effects of chronic social defeat stress on mouse self-grooming behavior and
      its patterning.
AB  - Stress induced by social defeat is a strong modifier of animal anxiety and
      depression-like phenotypes. Self-grooming is a common rodent behavior, and has an
      ordered cephalo-caudal progression from licking of the paws to head, body,
      genitals and tail. Acute stress is known to alter grooming activity levels and
      disrupt its patterning. Following 15-17 days of chronic social defeat stress,
      grooming behavior was analyzed in adult male C57BL/6J mice exhibiting either
      dominant or subordinate behavior. Our study showed that subordinate mice
      experience higher levels of anxiety and display disorganized patterning of their
      grooming behaviors, which emerges as a behavioral marker of chronic social
      stress. These findings indicate that chronic social stress modulates grooming
      behavior in mice, thus illustrating the importance of grooming phenotypes for
      neurobehavioral stress research.

PMID- 20060023
TI  - The cerebrovascular role of the cholinergic neural system in Alzheimer's disease.
AB  - The intrinsic cholinergic innervation of the cortical microvessels contains both
      subcortical pathways and local cortical interneurons mediated by muscarinic and
      nicotinic acetylcholine receptors. Stimulation of this system leads to
      vasodilatation. In the extrinsic innervation, choline acts as a selective agonist
      for the alpha7-nicoticinic acetylcholine receptor on the sympathetic nerves to
      cause vasodilatation, and through this mechanism, cholinergic modulation may
      affect this sympathetic vasodilatation. Alzheimer's disease is characterized by a
      cerebral cholinergic deficit and cerebral blood flow is diminished.
      Cholinesterase inhibitors, important drugs in the treatment of Alzheimer's
      disease, could influence the cerebral blood flow through stimulation of the
      intrinsic cholinergic cerebrovascular innervation. Indeed, cholinesterase
      inhibitors improve cerebral blood flow in Alzheimer patients who respond to
      treatment. Further, cerebrovascular reactivity and neurovascular coupling are
      impaired in Alzheimer's disease and both can be improved by cholinesterase
      inhibitors. Conversely, cholinesterase inhibitors inhibit the alpha7-nicoticinic
      acetylcholine receptor on extrinsic sympathetic nerves and thus may impair
      vasodilatation. The net outcome of these opposing effects in clinical practice
      remains unknown. Moreover, it is uncertain whether the regulation of cerebral
      blood flow during blood pressure changes (cerebral autoregulation) is impaired in
      patients with Alzheimer's disease. Technological developments now allow us to
      dynamically measure blood pressure, cerebral blood flow, and cerebral cortical
      oxygenation. Using simple maneuvers like single sit-stand and repeated sit-stand
      maneuvers, the regulation of cerebral perfusion in patients with Alzheimer's
      disease can easily be measured. Sit-stand maneuvers can be considered as a
      provocation test for cerebral autoregulation, and provide excellent opportunities
      to study the cerebrovascular effects of cholinesterase inhibitors.

PMID- 20060022
TI  - The cholinergic system and Parkinson disease.
AB  - Although Parkinson disease (PD) is viewed traditionally as a motor syndrome
      secondary to nigrostriatal dopaminergic denervation, recent studies emphasize non
      motor features. Non-motor comorbidities, such as cognitive impairment, are likely
      the result of an intricate interplay of multi-system degenerations and
      neurotransmitter deficiencies extending beyond the loss of dopaminergic nigral
      neurons. The pathological hallmark of parkinsonian dementia is the presence of
      extra-nigral Lewy bodies that can be accompanied by other pathologies, such as
      senile plaques. Lewy first identified the eponymous Lewy body in neurons of the
      nucleus basalis of Meynert (nbM), the source of cholinergic innervation of the
      cerebral cortex. Although cholinergic denervation is recognized as a pathological
      hallmark of Alzheimer disease (AD), in vivo neuroimaging studies reveal loss of
      cerebral cholinergic markers in parkinsonian dementia similar to or more severe
      than in prototypical AD. Imaging studies agree with post-mortem evidence
      suggesting that basal forebrain cholinergic system degeneration appears early in
      PD and worsens coincident with the appearance of dementia. Early cholinergic
      denervation in PD without dementia appears to be heterogeneous and may make
      specific contributions to the PD clinical phenotype. Apart from well-known
      cognitive and behavioral deficits, central, in particular limbic, cholinergic
      denervation may be associated with progressive deficits of odor identification in
      PD. Recent evidence indicates also that subcortical cholinergic denervation,
      probably due to degeneration of brainstem pedunculopontine nucleus neurons, may
      relate to the presence of dopamine non-responsive gait and balance impairments,
      including falls, in PD.

PMID- 20060024
TI  - Development and optimization of a doxorubicin loaded poly(lactic acid) contrast
      agent for ultrasound directed drug delivery.
AB  - An echogenic, intravenous drug delivery platform is proposed in which an
      encapsulated chemotherapeutic can travel to a desired location and drug delivery
      can be triggered using external, focused ultrasound at the area of interest.
      Three methods of loading poly(lactic acid) (PLA) shelled ultrasound contrast
      agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency,
      in vitro enhancement, stability, particle size, morphology and release during UCA
      rupture are compared by loading method and drug concentration. An agent
      containing doxorubicin within the shell was selected as an ideal candidate for
      future hepatocellular carcinoma studies. The agent achieved a maximal drug load
      of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth
      surface morphology and tight size distribution (poly dispersity index=0.309) with
      a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in
      vitro at a dosage of 10 microg/ml, with a half life of over 15 min. In vivo, the
      agent provided ultrasound enhancement of 13.4+/-1.6 dB within the ascending aorta
      of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent
      is thought to be well suited for future drug delivery experiments, this study has
      shown that agent properties can be tailored for specific applications based on
      choice of drug loading method.

PMID- 20060025
TI  - Characterization of a profile of the anthocyanins isolated from Vitis coignetiae
      Pulliat and their anti-invasive activity on HT-29 human colon cancer cells.
AB  - We isolated anthocyanins from fruits of Vitis coignetiae Pulliat, characterized
      the anthocyanin profile, and investigated the anti-invasive effects of the
      anthocyanins on human colon cancer cells. The anthocyanins inhibited cell
      invasion in a dose-dependent manner, as measured by Matrigel invasion assays, by
      suppression of matrix metalloproteinase (MMP)-2 and MMP-9 expression. The anti
      invasive activity of the anthocyanins was associated with modulation of
      constitutive nuclear factor kappaB (NF-kappaB) activation. The activation of NF
      kappaB triggered by tumor necrosis factor-alpha was also inhibited by the
      anthocyanins through suppression IkappaBalpha phosphorylation. AIMs inhibited the
      expression of NF-kappaB-regulated proteins. In conclusion, this study suggested
      that the anthocyanins isolated from fruits of V. coignetiae Pulliat should have
      anti-invasive activities on human colon cancer cells and the activities should be
      related to the inhibition of NF-kappaB-regulated proteins such as MMP-2 and MMP-9
      expression through the inhibition of NF-kappaB activation.

PMID- 20060026
TI  - Estimation of ochratoxin A in some Turkish populations: an analysis in urine as a
      simple, sensitive and reliable biomarker.
AB  - In this study, ochratoxin A (OTA) occurrence and level in human urine samples,
      collected from four different regions of Turkey was analyzed by NaHCO(3)
      dilution, immunoaffinity column clean-up and high-performance liquid
      chromatography with fluorescent detection. For the repeatability of the method,
      RSD (%) values were found between 3.83 and 8.86, for the accuracy, the recovery
      values were found between 85.7% and 110.5% and limit of detection and limit of
      quantification of the method were measured as 0.006 and 0.018 ng mL(-1)
      respectively. For the analysis, first morning urine samples were collected and
      the results were adjusted with creatinine levels. From the total collected
      samples of 233 larger amounts of 83% was contaminated with OTA. Among the
      calculated to be OTA levels, positive sample rate, average OTA amount and the
      highest contamination was found in Ankara. (Positive sample rate; 90.1%, average
      OTA concentration; 14.34 ng g(-1) creatinine and highest OTA value; 75.60 ng g(
      1) creatinine). In order to define the exposure profile of OTA in human a
      questionnaire was conducted among the voluntaries as well. But related to the
      gender, age, dietary habits, coffee consumption, smoking and alcohol habits of
      the volunteers, no correlation was found with the OTA exposure.

PMID- 20060028
TI  - Flame atomic absorption spectrometric determination of copper, zinc and manganese
      after solid-phase extraction using 2,6-dichlorophenyl-3,3-bis(indolyl)methane
      loaded on Amberlite XAD-16.
AB  - A simple and selective method for the determination of Cu(2+), Zn(2+) and Mn(2+)
      ions in real samples by FAAS after solid-phase extraction was developed. The
      method is based on the sorption of metal ions on Amberlite XAD-16 modified by 3
      ((2,6-dichlorophenyl)(1H-indol-3-yl)methyl)-1H-indole (DCPIMI) at a pH of 5.0.
      The metal ions retained on solid phase by complexation with ligand were then
      eluted with 6 mL of 4 mol L(-1) nitric acid in acetone. In order to obtain a
      reversible uptake and elution of metal ions, the influence of flow rates of
      eluent and sample solution, ligand concentration and amount of surfactant and
      condition of elution solution was also investigated. A preconcentration factor of
      225 was achieved by passing 1350 mL of sample through the solid phase, while the
      limit of detection (LOD) of Cu(2+), Zn(2+) and Mn(2+) ions were found to be 1.9,
      1.5 and 2.6 ng mL(-1), respectively, and the corresponding precision at 20 microg
      L(-1) was 2.1%, 2.3%, 3.0%.

PMID- 20060027
TI  - Chronic high fat, high cholesterol supplementation decreases 18 kDa Translocator
      Protein binding capacity in association with increased oxidative stress in rat
      liver and aorta.
AB  - It is well known that high fat and high cholesterol levels present a contributing
      factor to pathologies including fatty liver and atherosclerosis. Oxidative stress
      is also considered to play a role in these pathologies. The 18 kDa Translocator
      Protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, is
      known to be involved in cholesterol metabolism, oxidative stress, and
      cardiovascular pathology. We applied a high fat high cholesterol atherogenic
      (HFHC) diet to rats to study correlations between cardiovascular and liver
      pathology, oxidative stress, and TSPO expression in the liver and the
      cardiovascular system. This study corroborates the presence of increased
      oxidative stress markers and decreased anti-oxidants in liver and aorta. In
      addition, it appeared that induction of oxidative stress in the liver and aorta
      by atherogenic HFHC diet was accompanied by a reduction in TSPO binding density
      in both these tissues. Our data suggest that involvement of TSPO in oxidative
      stress and ROS generation, as reported in other studies, may also take part in
      atherogenesis as induced by HFHC diet. Presently, it is not clear whether this
      TSPO response is compensatory for the stress induced by HFHC diet or is a
      participant in the induction of oxidative stress.

PMID- 20060029
TI  - Toxicological evaluation of Tetracarpidium conophorum nut oil-based diet in rats.
AB  - The effects of Tetracarpidium conophorum nut oil-based diet on the growth
      performance and some biochemical constituents of rat tissues was investigated
      following a feeding period of 6 weeks. The results revealed that the volume of
      water taken, the amount of feed consumed and the weight gained by the animals
      maintained on the nut oil-based diet were not significantly (P>0.05) different
      from those fed on soybean oil-based diet. The reduction in the activities of ALP,
      GOT and GPT in the liver and heart of animals fed on the nut oil-based diet was
      accompanied by increase in the serum enzymes. The nut oil-based diet
      significantly reduced (P<0.05) serum concentrations of total cholesterol and HDL
      C whereas triglycerides and atherogenic index increased. The serum LDL-C level of
      the nut oil-based diet fed animals compared well with those of soybean oil-based
      diet. These alterations suggested that adverse effects have occurred, possibly by
      altered membrane permeability of the hepatocytes and cardiac cells. Similar
      alterations in the serum lipids of animals maintained on nut oil-based diet also
      portends cardiovascular risk. Although, T. conophorum nut oil did not adversely
      affect growth performance and the feeding appetite of the animals, it is not
      completely 'safe' for consumption.

PMID- 20060030
TI  - Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8
      pathway in lung cancer A549 cells.
AB  - Indole-3-carbinol (I3C) has anti-tumor effects in various cancer cell lines.
      However, the anti-tumor effect of I3C on human lung cancers has been rarely
      reported. We investigated the anti-tumor effects and its mechanism of I3C on
      human lung carcinoma A549 cell line. Treatment of the A549 cells with I3C
      significantly reduced cell proliferation, increased formations of fragmented DNA
      and apoptotic body, and induced cell cycle arrest at G0/G1 phase. I3C increased
      not only the protein levels of cyclin D1, phosphorylated p53, and p21 but also
      the expression of Fas mRNA. Cleavage of caspase-9, -8, -3 and PARP also was
      increased by I3C. Treatment with wortmannin significantly suppressed both I3C
      induced Ser15 phosphorylation and accumulation of p53 protein. The inhibition of
      caspase-8 by z-IETD-FMK significantly decreased cleavage of procaspase-8,-3 and
      PARP in I3C-treated A549 cells. Taken together, these results demonstrate that
      I3C induces cell cycle arrest at G0/G1 through the activation of p-p53 at Ser 15
      and induces caspase-8 mediated apoptosis via the Fas death receptor. This
      molecular mechanism for apoptotic effect of I3C on A549 lung carcinoma cells may
      be a first report and suggest that I3C may be a preventive and therapeutic agent
      against lung cancer.

PMID- 20060031
TI  - Effects of cloned-cattle meat diet on reproductive parameters in pregnant
      rabbits.
AB  - In this paper, we report on the effects of a diet containing cloned-cattle meat
      on the reproductive parameters in pregnant rabbits. The artificially inseminated
      rabbits (gestation day 0) were fed a diet containing 5% or 10% of normal or
      cloned-cattle meat during the gestation period. Rabbits fed commercial pellet (no
      additional supplementations) were used as the control. Supplementation of cloned
      cattle meat diets did not have any toxicologically significant effects on
      reproductive performance in dams (body weight, clinical signs, organ weight, and
      cesarean section analysis). And it also did not affect on fetal development (body
      and placental weight, and external, visceral and skeletal findings) compared to
      the controls. The only difference was a food consumption in the first week of
      gestation for all meat-based diet groups (p<0.05, 0.01, and 0.001, respectively).
      Our results collectively suggest that there are no obvious differences in
      reproductive parameters in pregnant rabbits fed cloned-cattle meat.

PMID- 20060032
TI  - Potentiating effect of endothelial cells on astrocytic plasminogen activator
      inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier.
AB  - There is accumulating evidence of the importance of cellular communication
      between the cells that compose the blood-brain barrier (BBB). Astrocytes are
      known to affect the expression of tissue-type plasminogen activator (t-PA) and
      its inhibitor plasminogen activator inhibitor type-1 (PAI-1) in endothelial
      cells. We investigated the influence of endothelial cells on astrocytic gene
      expression of PAI-1, protease nexin-1 (PN-1) and t-PA using an in vitro model of
      the BBB. Primary rat astrocyte-enriched cultures were cocultured with primary
      adult rat brain microvascular endothelial cells on opposite sides of a transwell
      membrane. After coculturing for 9-11 days, the cultures were treated with
      lipopolysaccharide (LPS) for 8 h or 24 h. The levels of PAI-1, PN-1 and t-PA mRNA
      in untreated and treated monocultures and cocultures were analyzed by Real-Time
      RT-PCR. Cocultivation of astrocytes and endothelial cells increased astrocytic
      PAI-1 mRNA expression, and this response was further amplified by LPS treatment.
      The levels of PN-1 and t-PA mRNA expression in astrocytes were unaffected by
      cocultivation and/or LPS treatment. Analysis of endothelial PAI-1 and t-PA gene
      expression revealed increased PAI-1 mRNA levels in cocultured cells, whereas t-PA
      mRNA levels remained unchanged. These results demonstrate that the cocultivation
      of astrocytes and endothelial cells induces a pronounced increase in astrocytic
      PAI-1 gene expression, and that this effect is amplified by LPS treatment. These
      findings imply an important role for intercellular crosstalk in modulating PAI-1
      gene expression within the BBB, under both physiologic and pathophysiologic
      conditions.

PMID- 20060033
TI  - Histone deacetylase inhibition enhances adenoviral vector transduction in inner
      ear tissue.
AB  - Adenovirus vectors (AdVs) are efficient tools for gene therapy in many tissues.
      Several studies have demonstrated successful transgene transduction with AdVs in
      the inner ear of rodents [Kawamoto K, Ishimoto SI, Minoda R, Brough DE, Raphael Y
      (2003) J Neurosci 23:4395-4400]. However, toxicity of AdVs [Morral N, O'Neal WK,
      Rice K, Leland MM, Piedra PA, Aguilar-Cordova E, Carey KD, Beaudet AL, Langston C
      (2002) Hum Gene Ther 13:143-154.] or lack of tropism to important cell types such
      as hair cells [Shou J, Zheng JL, Gao WQ (2003) Mol Cell Neurosci 23:169-179]
      appears to limit their experimental and potential clinical utility. Histone
      deacetylase inhibitors (HDIs) are known to enhance AdV-mediated transgene
      expression in various organs [Dion LD, Goldsmith KT, Tang DC, Engler JA, Yoshida
      M, Garver RI Jr (1997) Virology 231:201-209], but their effects in the inner ear
      have not been documented. We investigated the ability of one HDI, trichostatin A
      (TSA), to enhance AdV-mediated transgene expression in inner ear tissue. We
      cultured neonatal rat macular and cochlear explants, and transduced them with an
      AdV encoding green fluorescent protein (Ad-GFP) under the control of a
      constitutive promoter for 24 h. In the absence of TSA, GFP expression was
      limited, and very few hair cells were transduced. TSA did not enhance
      transduction when applied at the onset of Ad-GFP transduction. However,
      administration of TSA during or just after Ad-GFP application increased GFP
      expression in supporting cells approximately fourfold. Moreover, vestibular hair
      cell transduction was enhanced approximately sixfold, and that of inner hair
      cells by more than 17-fold. These results suggest that TSA increases AdV-mediated
      transgene expression in the inner ear, including the successful transduction of
      hair cells. HDIs, some of which are currently under clinical trials (Sandor et
      al., 2002), could be useful tools in overcoming current limitations of gene
      therapy in the inner ear using Ad-GFP.

PMID- 20060035
TI  - Properties of synaptic transmission from the reticular formation dorsal to the
      facial nucleus to trigeminal motoneurons during early postnatal development in
      rats.
AB  - We previously reported that electrical stimulation of the reticular formation
      dorsal to the facial nucleus (RdVII) elicited excitatory masseter responses at
      short latencies and that RdVII neurons were antidromically activated by
      stimulation of the trigeminal motor nucleus (MoV), suggesting that excitatory
      premotor neurons targeting the MoV are likely located in the RdVII. We thus
      examined the properties of synaptic transmission from the RdVII to jaw-closing
      and jaw-opening motoneurons in horizontal brainstem preparations from developing
      rats using voltage-sensitive dye, patch-clamp recordings and laser
      photostimulation. Electrical stimulation of the RdVII evoked optical responses in
      the MoV. Combined bath application of the non-N-methyl-d-aspartate (non-NMDA)
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and the NMDA
      receptor antagonist DL-2-amino-5-phosphonopentanoic acid (APV) reduced these
      optical responses, and addition of the glycine receptor antagonist strychnine and
      the GABA(A) receptor antagonist bicuculline further reduced the remaining
      responses. Electrical stimulation of the RdVII evoked postsynaptic currents
      (PSCs) in all 19 masseter motoneurons tested in postnatal day (P)1-4 rats, and
      application of CNQX and the NMDA receptor antagonist (+/-)-3(2-carboxypiperazin-4
      yl)propyl-1-phosphonic acid (CPP) reduced the PSC amplitudes by more than 50%. In
      the presence of CNQX and CPP, the GABA(A) receptor antagonist SR95531 further
      reduced PSC amplitude, and addition of strychnine abolished the remaining PSCs.
      Photostimulation of the RdVII with caged glutamate also evoked PSCs in masseter
      motoneurons of P3-4 rats. In P8-11 rats, electrical stimulation of the RdVII also
      evoked PSCs in all 14 masseter motoneurons tested, and the effects of the
      antagonists on the PSCs were similar to those in P1-4 rats. On the other hand,
      RdVII stimulation evoked PSCs in only three of 16 digastric motoneurons tested.
      These results suggest that both neonatal and juvenile jaw-closing motoneurons
      receive strong synaptic inputs from the RdVII through activation of glutamate,
      glycine and GABA(A) receptors, whereas inputs from the RdVII to jaw-opening
      motoneurons seem to be weak.

PMID- 20060034
TI  - Hippocampal cells encode places by forming small anatomical clusters.
AB  - The hippocampus has been hypothesized to function as a "spatial" or "cognitive"
      map, however, the functional cellular organization of the spatial map remains a
      mystery. The majority of electrophysiological studies, thus far, have supported
      the view of a random-type organization in the hippocampus. However, using
      immediate early genes (IEGs) as an indicator of neuronal activity, we recently
      observed a cluster-type organization of hippocampal principal cells, whereby a
      small number ( approximately 4) of nearby cells were activated in rats exposed to
      a restricted part of an environment. To determine the fine structure of these
      clusters and to provide a 3D image of active hippocampal cells that encode for
      different parts of an environment, we established a functional mapping of IEGs
      zif268 and Homer1a, using in situ hybridization and 3D-reconstruction imaging
      methods. We found that, in rats exposed to the same location twice, there were
      significantly more double IEG-expressing cells, and the clusters of nearby cells
      were more "tightly" formed, in comparison to rats exposed to two different
      locations. We propose that spatial encoding recruits specific cell ensembles in
      the hippocampus and that with repeated exposure to the same place the ensembles
      become better organized to more accurately represent the "spatial map."

PMID- 20060036
TI  - Induced NG2 expressing microglia in the facial motor nucleus after facial nerve
      axotomy.
AB  - Chondroitin sulfate proteoglycan (NG2) expressing cells, ubiquitously distributed
      in the CNS respond to injured or diseased neurons; however, their behaviors
      toward injured neurons have remained to be fully explored. In the present study,
      along with astrocytic and microglial responses, NG2 expressing cells reacted
      swiftly and robustly in the facial motor nucleus (FMN) subjected to axotomy. With
      time, hypertrophic NG2 expressing cells gradually adhered to and enwrapped the
      axotomized motoneurons. Tight encapsulations around axotomized motoneurons were
      eventually formed at 7, 14, and 28 days after axotomy. NG2 positive processes
      appeared to interpose between synapsin-1 immunoreactive nerve terminals and
      surfaces of axotomized motoneurons. Double labeling results showed that NG2
      expressing cells encapsulating axotomized facial motoneurons were mainly
      microglia marked by OX42 and lectin; only a few of them were positive to platelet
      derived growth factor-alpha receptor and none of them positive to ED-1. No
      Rhodamine particle was detected in the FMN ipsilateral to axotomy after venous
      injection of the particles. The results suggest that activated microglia in
      lesioned FMN were induced to express NG2 molecules. It is concluded that
      axotomized FMN showed two types of NG2 expressing cells namely constitutive NG2
      cells and induced-NG2 expressing microglia.

PMID- 20060038
TI  - Hazardous nature of high-temporal-frequency strobe light stimulation: neural
      mechanisms revealed by magnetoencephalography.
AB  - Individuals in contemporary society are continually exposed to various visual
      stimuli. Such stimulation, especially when high in temporal frequency, may
      sometimes cause unexpected events such as photosensitive seizures. Although many
      studies have demonstrated that high-temporal-frequency (>3 Hz) visual stimulation
      can yield hazardous responses in the CNS, the mechanisms by which it does so are
      still unclear. We therefore investigated the mechanisms of neural perturbation by
      high-temporal-frequency strobe light stimulation with high-temporal-frequency
      resolution (4-20 Hz with an interval of 2 Hz) using magnetoencephalography with
      high temporal and spatial resolution. We show that (1) three temporal dipole
      phases (phases 1, 2 and 3, by time course) can be identified in the visual evoked
      magnetic fields (VEF's) across stimulation frequencies based on the goodness-of
      fit values for equivalent current dipole estimation and horizontal dipole
      directions, (2) the dipole moment of VEF's is correlated with autonomic nervous
      system activity in phases 1 and 2, (3) some temporal stimulation frequencies
      enhance magnetic responses in phases 1, 2 and 3, and (4) these frequencies are
      harmonically related, with a greatest common divisor frequency (fundamental
      frequency) of approximately 6.5 Hz. Our clarification of the temporal frequency
      characteristics of VEF's will contribute to understanding of the potential
      hazardous effects of high-temporal-frequency strobe light stimulation in the CNS.

PMID- 20060037
TI  - Syntaxin 3B is essential for the exocytosis of synaptic vesicles in ribbon
      synapses of the retina.
AB  - Ribbon synapses of the vertebrate retina are specialized synapses that release
      neurotransmitter by synaptic vesicle exocytosis in a manner that is proportional
      to the level of depolarization of the cell. This release property is different
      from conventional neurons, in which the release of neurotransmitter occurs as a
      short-lived burst triggered by an action potential. Synaptic vesicle exocytosis
      is a calcium regulated process that is dependent on a set of interacting synaptic
      proteins that form the so-called SNARE (soluble N-ethylmaleimide sensitive factor
      attachment protein receptor) complex. Syntaxin 3B has been identified as a
      specialized SNARE molecule in ribbon synapses of the rodent retina. However, the
      best physiologically-characterized neuron that forms ribbon-style synapses is the
      rod-dominant or Mb1 bipolar cell of the goldfish retina. We report here the
      molecular characterization of syntaxin 3B from the goldfish retina. Using a
      combination of reverse transcription (RT) polymerase chain reaction (PCR) and
      immunostaining with a specific antibody, we show that syntaxin 3B is highly
      enriched in the plasma membrane of bipolar cell synaptic terminals of the
      goldfish retina. Using membrane capacitance measurements we demonstrate that a
      peptide derived from goldfish syntaxin 3B inhibits synaptic vesicle exocytosis.
      These experiments demonstrate that syntaxin 3B is an important factor for
      synaptic vesicle exocytosis in ribbon synapses of the vertebrate retina.

PMID- 20060039
TI  - Complex analysis of neuronal spike trains of deep brain nuclei in patients with
      Parkinson's disease.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been used to
      alleviate symptoms of Parkinson's disease. During image-guided stereotactic
      surgery, signals from microelectrode recordings are used to distinguish the STN
      from adjacent areas, particularly from the substantia nigra pars reticulata
      (SNr). Neuronal firing patterns based on interspike intervals (ISI) are commonly
      used. In the present study, arrival time-based measures, including Lempel-Ziv
      complexity and deviation-from-Poisson index were employed. Our results revealed
      significant differences in the arrival time-based measures among non-motor STN,
      motor STN and SNr and better discrimination than the ISI-based measures. The
      larger deviations from the Poisson process in the SNr implied less complex
      dynamics of neuronal discharges. If spike classification was not used, the
      arrival time-based measures still produced statistical differences among STN
      subdivisions and SNr, but the ISI-based measures only showed significant
      differences between motor and non-motor STN. Arrival time-based measures are less
      affected by spike misclassifications, and may be used as an adjunct for the
      identification of the STN during microelectrode targeting.

PMID- 20060040
TI  - Sequence divergence and expression of a transformer gene in the branchiopod
      crustacean, Daphnia magna.
AB  - Environmental decline triggers a switch in reproductive strategy of Daphnia magna
      from asexual to sexual reproduction; however, the molecular basis of such
      environmental sex determination remains largely unknown. In insects most closely
      related to branchiopod crustaceans, orthologs of the Drosophila transformer gene
      such as dipteran transformer (tra), honeybee feminizer (fem) and complementary
      sex determiner (csd) function as sex determining factors. Therefore, we cloned a
      D. magna transformer gene (dmagtra) and analyzed its expression. The predicted
      amino acid sequence has 380 amino acids including an arginine-serine-rich region,
      which is characteristic of insect orthologs of Tra. Residues 180 to 205 are
      highly conserved with known Tra orthologs. The domain organization of DmagTra is
      distinct from known Tra orthologs; moreover, dmagtra does not display any
      detectable sexual dimorphic differences in expression or splicing patterns. We
      infer from these results that dmagtra may not be responsible for sex
      determination in D. magna.

PMID- 20060041
TI  - An efficient algorithm to identify coordinately activated transcription factors.
AB  - Identification of transcription factor (TF) activities associated with a certain
      physiological/experimental condition is one of the preliminary steps to
      reconstruct transcriptional regulatory networks and to identify signal
      transduction pathways. TF activities are often indicated by the activities of its
      target genes. Existing studies on identifying TF activities through target genes
      usually assume the equivalence between co-regulation and co-expression. However,
      genes with correlated expression profiles may not be co-regulated. In the mean
      time, although multiple TFs can be activated coordinately, there is a lack of
      efficient methods to identify coordinately activated TFs. In this paper, we
      propose an efficient algorithm embedding a dynamic programming procedure to
      identify a subset of TFs that are potentially coordinately activated under a
      given condition by utilizing ranked lists of differentially expressed target
      genes. Applying our algorithm to microarray expression data sets for a number of
      diseases, our approach found subsets of TFs that are highly likely associated
      with the given disease processes.

PMID- 20060042
TI  - The regulation of expression of insect cuticle protein genes.
AB  - The exoskeleton of insects (cuticle) is an assembly of chitin and cuticle
      proteins. Its physical properties are determined largely by the proteins it
      contains, and vary widely with developmental stages and body regions. The genes
      encoding cuticle proteins are therefore good models to study the molecular
      mechanisms of signalling by ecdysteroids and juvenile hormones, which regulate
      molting and metamorphosis in insects. This review summarizes the studies of
      hormonal regulation of insect cuticle protein genes, and the recent progress in
      the analysis of the regulatory sequences and transcription factors important for
      their expression.

PMID- 20060043
TI  - On the physico-chemical and physiological requirements of hemozoin formation
      promoted by perimicrovillar membranes in Rhodnius prolixus midgut.
AB  - Triatomine insects are obligatory blood-feeders that detoxify most of the
      hemoglobin-derived heme through its crystallization into hemozoin (Hz). Previous
      evidence demonstrates the key role of midgut perimicrovillar membranes (PMVM) on
      heme crystallization in triatomines. Here, we investigated some of the physico
      chemical and physiological aspects of heme crystallization induced by Rhodnius
      prolixus PMVM. Hz formation in vitro proceeded optimally at pH 4.8 and 28 degrees
      C, apparently involving three kinetically distinct mechanisms along this process.
      Furthermore, the insect feeding status and age affected PMVM-induced heme
      crystallization whereas pharmacological blockage of PMVM formation by
      azadirachtin, reduced hemoglobin digestion and Hz formation in vivo. Mossbauer
      spectrometry analyses of R. prolixus midgut showed that Hz represents the only
      measurable iron species found four days after a blood meal. Autocatalytic heme
      crystallization to Hz is revealed to be an inefficient process and this
      conversion is further reduced as the Hz concentration increases. Also, PMVM
      derived lipids were able to induce rapid Hz formation, regardless of the diet
      composition. These results indicate that PMVM-driven Hz formation in R. prolixus
      midgut occurs at physiologically relevant physico-chemical conditions and that
      lipids derived from this structure play an important role in heme
      crystallization.

PMID- 20060044
TI  - Neuropeptide signaling sequences identified by pyrosequencing of the American dog
      tick synganglion transcriptome during blood feeding and reproduction.
AB  - Ticks are important vectors of numerous pathogens that impact human and animal
      health. The tick central nervous system represents an understudied area in tick
      biology and no tick synganglion-specific transcriptome has been described to
      date. Here we characterize whole or partial cDNA sequences of fourteen putative
      neuropeptides (allatostatin, insulin-like peptide, ion-transport peptide,
      sulfakinin, bursicon alpha/beta, eclosion hormone, glycoprotein hormone
      alpha/beta, corazonin, four orcokinins) and five neuropeptide receptors
      (gonadotropin receptor, leucokinin-like receptor, sulfakinin receptor, calcitonin
      receptor, pyrokinin receptor) translated from cDNA synthesized from the
      synganglion of unfed, partially fed and replete female American dog ticks,
      Dermacentor variabilis. Their homology to the same neuropeptides in other taxa is
      discussed. Many of these neuropeptides such as an allatostatin, insulin-like
      peptide, eclosion hormone, bursicon alpha and beta and glycoprotein hormone alpha
      and beta have not been previously described in the Chelicerata. An insulin
      receptor substrate protein was also found indicating that an insulin signaling
      network is present in ticks. A putative type-2 proprotein processing convertase
      was also sequenced that may be involved in cleavage at monobasic and dibasic
      endoproteolytic cleavage sites in prohormones. The possible physiological role of
      the proteins discovered in adult tick blood feeding and reproduction will be
      discussed.

PMID- 20060045
TI  - Mobilization of lipid stores in Manduca sexta: cDNA cloning and developmental
      expression of fat body triglyceride lipase, TGL.
AB  - Fatty acids stored as triglycerides (TG) in the fat body serve as precursor in
      multiple processes including energy production and synthesis of cellular
      components. Mobilization of fatty acids from TG depends on the action of lipases.
      The fat body triglyceride lipase from Manduca sexta, MsTGL, is the only insect
      lipase that has been purified and characterized, so far. A TGL cDNA from M. sexta
      fat body encoding a 649 amino acid protein was cloned and its identity confirmed
      by mass spectrometry and Edman sequencing data of the purified protein. The
      protein sequence has conserved domains and residues of potential importance for
      the function and regulation of TGL activity. The expression of TGL and the lipase
      activity of fat body homogenates were studied in several developmental stages of
      M. sexta. TG-hydrolase activity of fat body increased as larva grew to the last
      instar and, then, decreased to minimal levels during pupa stage. Lipase activity
      was progressively restored in adult insects and reached maximum values at this
      stage. The fat body lipase activity from adult insects, 1-2 day after emergence,
      was 9-fold higher than that from 2 to 3 days old 5th-instar larvae. A good
      correlation was found between the abundance of TGL protein and the lipase
      activity of fat body homogenates. This correlation and the expression pattern of
      TGL throughout development are consistent with the notion that TGL is the main
      fat body TG lipase of M. sexta.

PMID- 20060046
TI  - Accurate and objective copy number profiling using real-time quantitative PCR.
AB  - Copy number changes are known to be involved in numerous human genetic disorders.
      In this context, qPCR-based copy number screening may serve as the method of
      choice for targeted screening of the relevant disease genes and their surrounding
      regulatory landscapes. qPCR has many advantages over alternative methods, such as
      its low consumable and instrumentation costs, fast turnaround and assay
      development time, high sensitivity and open format (independent of a single
      supplier). In this chapter we provide all relevant information for a successfully
      implement of qPCR-based copy number analysis. We emphasize the significance of
      thorough in silico and empirical validation of the primers, the need for a well
      thought-out experiment design, and the importance of quality controls along the
      entire workflow. Furthermore, we suggest an appropriate and practical way to
      calculate copy numbers and to objectively interpret the results. The provided
      guidelines will most certainly improve the quality and reliability of your qPCR
      based copy number screening.

PMID- 20060047
TI  - Examining the contents of isolated Xenopus germinal vesicles.
AB  - One can manually isolate the giant oocyte nucleus or germinal vesicle (GV) of
      Xenopus from a living oocyte with nothing more complicated than jewelers' forceps
      and a dissecting microscope. Similarly, one can remove the nuclear envelope by
      hand and allow the lampbrush chromosomes and other nuclear organelles to spread
      on a microscope slide. After centrifugation, the nuclear contents adhere tightly
      to the slide, where they can be subjected to immunostaining or fluorescent in
      situ hybridization for visualization by conventional or confocal microscopy.
      Preparations of isolated GV contents reveal details of nuclear structure that are
      almost impossible to attain by more conventional techniques.

PMID- 20060048
TI  - Regional brain atrophy in primary fatigued patients with multiple sclerosis.
AB  - OBJECTIVE: To examine the relationship between fatigue, regional brain atrophy
      and normal appearing white matter damage in patients with multiple sclerosis.
      METHODS: Primary fatigued (PF) (n, 17) and non-fatigued (NF) (n, 17) patients
      with relapsing remitting multiple sclerosis and moderate disability were grouped
      according to their subjective fatigue score. Also, they were examined with
      respect to processing speed and central motor activation during isometric
      contraction. Using 3 Tesla MRI quantitative analyses were performed on normal
      appearing brain tissue and of brain structure volumes with tensor based
      morphometry. RESULTS: Between the PF and NF patients there was no significant
      differences in brain parenchymal fraction (81.5% vs. 82.4%), lesion load (0.53%
      vs. 0.36%) and NAA/Cr ratio (1.29 vs. 1.32 respectively). Eleven clusters of
      atrophy in PF versus NF involved gray and nearby white matter, the majority being
      located in areas functionally related to attentional control. Central motor
      activation was associated with atrophy in five regions in PF patients, three
      clusters involving the premotor and primary motor cortex. Normal appearing white
      matter did not differ between groups. CONCLUSION: Primary fatigued patients with
      multiple sclerosis have extended regional atrophy of supratentorial brain
      parenchyma, involving the cerebral cortex, nearby white matter and the caudate
      head, areas which are functionally related to attentional control. We suggest
      that impaired central motor activation is due to interruption of the cortico
      subcortical motor circuits involving the motor cortex.

PMID- 20060049
TI  - Effects of ApoE-epsilon4 allele load and age on the rates of grey matter and
      hippocampal volumes loss in a longitudinal cohort of 1186 healthy elderly
      persons.
AB  - In a sample of 1186 healthy subjects aged 65 to 89 years who were scanned twice
      with MRI 3.6 years apart, we studied the effects of age and ApoE-epsilon4 allele
      load on the rate of atrophy of grey matter and hippocampus. Rates of grey matter
      and hippocampal volumes loss were computed from T1-weighted magnetic resonance
      images using voxel-based morphometry and region of interest analysis.
      Longitudinal analysis showed that an age-related annual rate of grey matter
      volume loss was only seen in epsilon4 homozygotes only (n=14) whereas no age
      effect was seen epsilon4 heterozygotes (n=239) and in noncarriers (n=933). ApoE
      epsilon4 homozygotes also had a significantly larger rate of hippocampal volume
      loss than heterozygotes or noncarriers. During the same period, no effect or
      interaction of ApoE genotype and age was observed on cognitive decline, as
      assessed by the Mini Mental State Examination (MMSE). These data do not suggest
      an epsilon4 gene dose effect on the rate of hippocampal volume loss in healthy
      elderly subjects as most of the effect was limited to homozygotes. Hippocampal
      volume loss may not be a good imaging marker to understand the effect of the ApoE
      epsilon4 allele on the risk of dementia in a population-based setting. It could
      be hypothesized that the impact of a single ApoE-epsilon4 allele on brain
      structures is largely delayed in time.

PMID- 20060051
TI  - Molecular phylogeny of acariform mites (Acari, Arachnida): strong conflict
      between phylogenetic signal and long-branch attraction artifacts.
AB  - Acariformes (one of the two main lineages of Acari) represent an exceptionally
      diverse group of Arachnida. We performed first comprehensive phylogenetic
      analysis of Acariformes using sequence data from the nuclear small subunit rRNA
      gene (18S rDNA) and the mitochondrial cytochrome c oxidase subunit I (COI, amino
      acids). Our analyses confirm the monophyly of Acariformes and recognize two
      orders within Acariformes: Sarcoptiformes, consisting of Endeostigmata and
      Oribatida+Astigmata, and Trombidiformes. The data revealed the origin of
      Astigmata within Oribatida with the desmonomatan superfamily Crotonioidea as the
      source of astigmatan radiation and the sexual family Hermanniidae as the sister
      group, which generally supports previous morphological hypotheses. These results
      were found despite the strong conflict between long-branch attraction (LBA)
      artifacts and phylogenetic signal. It is likely that the conflict resulted from
      differences in the substitution rates among acariform lineages, especially
      comparing slowly evolving Oribatida with rapidly evolving Astigmata. The use of
      likelihood methods considered more resistant to LBA only slightly decreased the
      chance of falling into the LBA trap; the probability of recovering the origin of
      Astigmata within Desmonomata differs only by about 10% from that of having the
      long branched Astigmata and Trombidiformes either connected directly or shifted
      to deep parts of the tree due to outgroup attraction. Molecular dating using the
      rate-smoothing method PATHd8 shows that Acariformes originated c. 435 MYA and
      were probably among the earliest arthropods invading terrestrial habitats in late
      Silurian or the Lower Devonian, when the first vascular plants are thought to
      have arisen. Our analyses did not support the monophyly of Acari because we
      recovered clades Acariformes-Solifugae and Parasitiformes-Pseudoscorpionida.
      However, a formal revision of arachnid classification that would reflect these
      results must await future analyses.

PMID- 20060050
TI  - Automatic search for fMRI connectivity mapping: an alternative to Granger
      causality testing using formal equivalences among SEM path modeling, VAR, and
      unified SEM.
AB  - Modeling the relationships among brain regions of interest (ROIs) carries unique
      potential to explicate how the brain orchestrates information processing.
      However, hurdles arise when using functional MRI data. Variation in ROI activity
      contains sequential dependencies and shared influences on synchronized
      activation. Consequently, both lagged and contemporaneous relationships must be
      considered for unbiased statistical parameter estimation. Identifying these
      relationships using a data-driven approach could guide theory-building regarding
      integrated processing. The present paper demonstrates how the unified SEM attends
      to both lagged and contemporaneous influences on ROI activity. Additionally, this
      paper offers an approach akin to Granger causality testing, Lagrange multiplier
      testing, for statistically identifying directional influence among ROIs and
      employs this approach using an automatic search procedure to arrive at the
      optimal model. Rationale for this equivalence is offered by explicating the
      formal relationships among path modeling, vector autoregression, and unified SEM.
      When applied to simulated data, biases in estimates which do not consider both
      lagged and contemporaneous paths become apparent. Finally, the use of unified SEM
      with the automatic search procedure is applied to an empirical data example.

PMID- 20060052
TI  - Effect of geological vicariance on mitochondrial DNA differentiation in Common
      Pheasant populations of the Loess Plateau and eastern China.
AB  - Population differentiation within species can be stimulated by various geographic
      and climatic factors. In this study, we analyzed the population structure of the
      Common Pheasant (Phasianus colchicus) in the Loess Plateau and its adjacent
      eastern areas (named eastern China). We sequenced mitochondrial cytochrome b and
      control regions of 249 samples collected from 42 populations that covered the
      whole Loess Plateau and eastern China. Two groups (one containing populations 1
      27 and the other populations 28-42) were identified using Analysis of Molecular
      Variance, Spatial Analysis of Molecular Variance, median-joining network analysis
      and maximum-parsimony analysis. The results demonstrated that although
      populations were distributed continuously throughout the study area, there was
      clear differentiation between populations. Geographically, population
      differentiation was sutured along the eastern edge of the Loess Plateau. The
      Migration Divergence (MDIV) analysis suggested that the two groups diverged at
      about 0.21 million years ago, which corresponded to a period when numerous large
      inland paleo-lakes greatly receded across the Loess Plateau during 0.25-0.20
      million years before present (Ma BP). We inferred that the rapid recession of the
      Loess Plateau paleo-lakes caused dramatic shifts from a relatively humid climate,
      to one that was significantly more arid. Such severe climate transition combined
      with a dry-cold starting of one of multi-cycled climate fluctuations from warm
      humid to dry-cold since about 0.24-0.22 Ma BP on the Loess Plateau may have been
      the impetus that effectively facilitated differentiation between different
      pheasant populations.

PMID- 20060053
TI  - Strong association between respiratory viral infection early after hematopoietic
      stem cell transplantation and the development of life-threatening acute and
      chronic alloimmune lung syndromes.
AB  - Alloimmune lung syndromes (allo-LS), including idiopathic pneumonia syndrome,
      bronchiolitis obliterans syndrome, and bronchiolitis obliterans organizing
      pneumonia, are severe complications after hematopoietic stem cell transplantation
      (HSCT). In our cohort of 110 pediatric patients, 30 had allo-LS (27.3%), 18 with
      idiopathic pneumonia syndrome and 12 with bronchiolitis obliterans syndrome.
      Multivariate analysis showed that respiratory viral infection early after HSCT is
      an important predictor for the development of allo-LS (P <.0001). This was true
      for all viruses tested. In multivariate analysis, allo-LS was the only predictor
      for higher mortality (P = .04). Paradoxically, prolonged administration of
      immunosuppressive agents because of acute graft-versus-host disease had a
      protective effect on the development of allo-LS (P = .004). We hypothesize that
      early infection of the respiratory tract with a common cold virus makes the lungs
      a target for alloimmunity.

PMID- 20060054
TI  - Inhibitory effects of diterpene acids from root of Aralia cordata on IgE-mediated
      asthma in guinea pigs.
AB  - This study evaluated the anti-asthmatic activities of four diterpene acids
      isolated from Aralia cordata root that are proposed to be the active ingredients
      in its traditional use as a treatment for inflammation, overheating, pain and
      spasm in Korea. The diterpene acids were identified as kaurenoic acid, 7-oxo
      sandaracopimaric acid, 17-hydroxy-ent-kaur-15-en-19-oic acid, and hederagenin, by
      comparing their phytochemical and spectroscopic data with previous reports. The
      effects of diterpene acids on asthma were evaluated by determining the specific
      airway resistance (sRaw) during the immediate asthmatic response (IAR) and the
      late-phase asthmatic response (LAR) in guinea pigs with IgE-mediated asthma.
      Recruitment of leukocytes and the presence of chemical mediators in
      bronchoalveolar lavage fluid (BALF) were determined, and histopathological
      surveys performed. The four diterpene acids dosed at 25 approximately 100 mg/kg
      had dose-dependently anti-asthmatic effects: 7-oxo-sandaracopimaric acid > 17
      hydroxy-ent-kaur-15-en-19-oic acid > kaurenoic acid > hederagenin. 7-oxo
      sandaracopimaric acid (25 mg/kg) significantly (p < 0.05) inhibited sRaw by 59.5%
      in IAR and LAR, and also dose-dependently inhibited recruitment of eosinophils
      and neutrophils into lung and release of chemical mediators, histamine, and the
      activity of phospholipase A(2) and eosinophil peroxidase in BALF. 7-Oxo
      sandaracopimaric acid had the highest activity among the diterpene acids. But its
      effect was lower than cromolyn sodium, salbutamol, or dexamethasone in both the
      IAR and the LAR. These results suggested that C(7)-oxo radical of 7-oxo
      sandaracopimaric acid was more active than the C(7)-hydroxy and hydrogen of the
      other compounds, and showed diterpene acids have anti-asthmatic effects,
      supporting the traditional application of this herb in treating IgE-mediated
      asthma.

PMID- 20060055
TI  - Fasting triggers hypothermia, and ambient temperature modulates its depth in
      Japanese quail Coturnix japonica.
AB  - We tested three hypotheses regarding the cues that elicit facultative hypothermia
      in Japanese quail (Coturnix japonica): H(1)) Ambient temperature (T(a)), alone,
      influences the onset and depth of hypothermia; H(2)) Fasting, alone, influences
      the onset and depth of hypothermia; H(3)) T(a) acts synergistically with fasting
      to shape the use of hypothermia. Eight quail were maintained within their
      thermoneutral zone (TNZ) at 32.6+/-0.2 degrees C, and eight below their lower
      critical temperature (T(lc)) at 12.7+/-3.0 degrees C. All quail entered
      hypothermia upon food deprivation, even quail kept within their TNZ. Body
      temperature (T(b)) decreased more (38.36+/-0.53 degrees C vs. 39.57+/-0.57
      degrees C), body mass (m(b)) loss was greater (21.0+/-7.20 g vs.12.8+/-2.62g),
      and the energy saved by using hypothermia was greater (25.18-45.01% vs. 7.98
      28.06%) in low the T(a) treatment than in TNZ treatment. Interestingly, the depth
      of hypothermia was positively correlated with m(b) loss in the low T(a)
      treatment, but not in TNZ treatment. Our data support H(3), that both
      thermoregulatory costs and body energy reserves are proximate cues for entry into
      hypothermia in quail. This outcome is not surprising below the T(lc). However,
      the quail kept at their TNZ also responded to food deprivation by entering
      hypothermia with no apparent dependence on m(b) loss. Therefore inputs, other
      than thermoregulatory costs and body condition, must serve as cues to enter
      hypothermia. Consequently, we address the role that tissue sparing may play in
      the physiological 'decision' to employ hypothermia.

PMID- 20060056
TI  - Starvation physiology: reviewing the different strategies animals use to survive
      a common challenge.
AB  - All animals face the possibility of limitations in food resources that could
      ultimately lead to starvation-induced mortality. The primary goal of this review
      is to characterize the various physiological strategies that allow different
      animals to survive starvation. The ancillary goals of this work are to identify
      areas in which investigations of starvation can be improved and to discuss recent
      advances and emerging directions in starvation research. The ubiquity of food
      limitation among animals, inconsistent terminology associated with starvation and
      fasting, and rationale for scientific investigations into starvation are
      discussed. Similarities and differences with regard to carbohydrate, lipid, and
      protein metabolism during starvation are also examined in a comparative context.
      Examples from the literature are used to underscore areas in which reporting and
      statistical practices, particularly those involved with starvation-induced
      changes in body composition and starvation-induced hypometabolism can be
      improved. The review concludes by highlighting several recent advances and
      promising research directions in starvation physiology. Because the hundreds of
      studies reviewed here vary so widely in their experimental designs and
      treatments, formal comparisons of starvation responses among studies and taxa are
      generally precluded; nevertheless, it is my aim to provide a starting point from
      which we may develop novel approaches, tools, and hypotheses to facilitate
      meaningful investigations into the physiology of starvation in animals.

PMID- 20060057
TI  - Superoxide production, oxidative damage and enzymatic antioxidant defenses in
      shark skeletal muscle.
AB  - Pelagic sharks, unlike teleost fish, require constant active swimming to obtain a
      suitable oxygen (O(2)) supply. An increase in O(2) consumption during exercise
      enhances production of reactive oxygen species (ROS). We hypothesized that shark
      species that display vigorous exercise, such as Isurus oxyrinchus and
      Carcharhinus falciformis, have higher ROS production and, in consequence, higher
      antioxidant enzyme activities in muscle in comparison with species with less
      active swimming, like Sphyrna zygaena. Superoxide radical (O(2)(*-)) production,
      lipid peroxidation levels (TBARS) and the activity of antioxidant enzymes:
      superoxide dismutase (total, t-SOD; manganese-dependent, Mn-SOD, and copper and
      zinc-dependent, Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione-S-transferase (GST) and glutathione reductase (GR), were measured by
      spectrophotometric assays in skeletal muscle extracts of three shark species (C.
      falciformis, I. oxyrinchus and S. zygaena). Higher O(2)(*-) production and GPx
      and GST activities (p<0.05) were found in C. falciformis and I. oxyrinchus than
      in S. zygaena. These results suggest that in antioxidant enzymes (GPx, GST)
      activity suffices to balance the production of ROS and to maintain lower TBARS
      levels (p<0.05) than in C. falciformis or S. zygaena, contributing to the
      capacity of I. oxyrinchus to maintain high muscular activity.

PMID- 20060058
TI  - The role of the kidney in compensating the alkaline tide, electrolyte load, and
      fluid balance disturbance associated with feeding in the freshwater rainbow
      trout, Oncorhynchus mykiss.
AB  - The effect in freshwater rainbow trout of digesting a commercial pellet meal on
      the renal handling of water, ions and acid-base equivalents was investigated
      through urine collection over a 48 h period following meal ingestion. The
      glomerular filtration rate (GFR) and urine flow rate (UFR) were reduced in fed
      fish between 12 and 24h following the meal, likely reflecting a loss of
      endogenous water across the gastric epithelium as a result of ingesting dry, ion
      rich food pellets. The kidney was also responsible for the excretion of some
      excess dietary Ca(2+), and, to a much lesser extent, Na(+) and Cl(-), while the
      urinary excretion of K(+) was unaffected. The most dramatic effect of feeding was
      the elevation of renal Mg(2+) excretion, with the kidney transitioning from net
      Mg(2+) reabsorption to net Mg(2+) secretion during digestion. The renal handling
      of dietary ions accounted for 3-27% of the total ions absorbed from the diet,
      indicating that a majority of the ions are excreted extra-renally or incorporated
      into growth. However this does highlight the underestimation of renal ion
      handling when using unfed fish models. The metabolic alkalosis created by
      digestion (the alkaline tide) resulted in an increase in urine pH as well as a
      transition from net acidic equivalent excretion in the urine to net basic
      equivalent excretion. This was due to a decrease in the titratable acidity minus
      bicarbonate component of urine as well as a decrease in ammonia secretion.
      Additionally, the experimental separation of the urinary component of acid-base
      excretion from that of the gills highlighted the substantially larger
      contribution of the latter. During the alkaline tide, renal excretion accounted
      for approximately 5% of the total basic equivalent excretion to the external
      water.

PMID- 20060059
TI  - Rapid dissection of a complex phenotype through genomic-scale mapping of fitness
      altering genes.
AB  - The understanding and engineering of complex phenotypes is a critical issue in
      biotechnology. Conventional approaches for engineering such phenotypes are often
      resource intensive, marginally effective, and unable to generate the level of
      biological understanding desired. Here, we report a new approach for rapidly
      dissecting a complex phenotype that is based upon the combination of genome-scale
      growth phenotype data, precisely targeted growth selections, and informatic
      strategies for abstracting and summarizing data onto coherent biological
      processes. We measured at high resolution (125 NT) and for the entire genome the
      effect of increased gene copy number on overall biological fitness corresponding
      to the expression of a complex phenotype (tolerance to 3-hydroxypropionic acid (3
      HP) in Escherichia coli). Genetic level fitness data were then mapped according
      to various definitions of gene-gene interaction in order to generate network
      level fitness data. When metabolic pathways were used to define interactions, we
      observed that genes within the chorismate and threonine super-pathways were
      disproportionately enriched throughout selections for 3-HP tolerance. Biochemical
      and genetic studies demonstrated that alleviation of inhibition of either of
      these super-pathways was sufficient to mitigate 3-HP toxicity. These data enabled
      the design of combinatorial modifications that almost completely offset 3-HP
      toxicity in minimal medium resulting in a 20 g/L and 25-fold increase in
      tolerance and specific growth, respectively.

PMID- 20060060
TI  - A genomic-library based discovery of a novel, possibly synthetic, acid-tolerance
      mechanism in Clostridium acetobutylicum involving non-coding RNAs and ribosomal
      RNA processing.
AB  - We generated a genomic library from sheared Clostridium acetobutylicum ATCC 824
      DNA, whereby inserts can be expressed in both directions from the thiolase
      promoter, P(thl). Serial transfer of library-bearing C. acetobutylicum cultures
      exposed to increasing butyrate concentrations enriched for inserts containing
      fragments of rRNA genetic loci. The selected library inserts were placed so that
      antisense (to the rRNAs) non-coding RNAs (ncRNAs) would be transcribed from
      P(thl). Different enriched inserts imparted similar butyrate-tolerance
      characteristics. A minimal tolerance fragment (RDNA7) was identified as the 16S
      rRNA promoter region. Expressed on plasmid pRD7 off P(thl), RDNA7 can produce
      putative ncRNAs termed ncRNA(RD7). C. acetobutylicum 824(pRD7) showed superior
      resistance to butyrate and other carboxylic acids. Transcriptional analysis of
      butyrate stress identified 120 differentially expressed genes between 824(pRD7)
      and 824(pSOS95del). The few upregulated genes included the ffh gene of the
      putative signal recognition particle (SRP) system. Northern analysis of
      ncRNA(RD7) and corresponding antisense RNAs demonstrated multiple ncRNA(RD7)
      molecules in 824(pRD7). Several corresponding antisense RNA molecules were
      identified both in 824(pRD7) and 824(pSOS95del), but at much higher levels in
      824(pRD7). Northern analysis of 16S rRNA expression suggested complex RDNA7
      dependent rRNA processing. Our data suggest that by hybridizing against
      unprocessed rRNA precursors, ncRNA(RD7) alters rRNA processing, and these
      alterations result in acid tolerance, possibly through a mechanism involving the
      Ffh protein.

PMID- 20060062
TI  - Histopathology, humoral and cellular immune response in the murine model of
      Leishmania (Viannia) shawi.
AB  - Leishmania (Viannia) shawi was recently characterized and few studies concerning
      modifications in cellular and humoral immune responses in experimental
      leishmaniasis have been conducted. In this work, immunopathological changes
      induced by L. shawi in chronically infected BALB/c mice were investigated.
      Infected BALB/c mice developed increased lesion size associated with strong
      inflammatory infiltrate diffusely distributed in the dermis, with highly infected
      macrophages. The humoral immune response was predominantly directed toward the
      IgG1 isotype. The functional activity of CD4(+) and CD8(+) T cells showed
      significantly increased TNF-alpha mRNA levels associated with reduced IFN-gamma
      expression by CD4(+) T cells and the double negative (dn) CD4CD8 cell subset.
      High IL-4 levels expressed by CD8(+) T cells and dnCD4CD8 and TGF-beta by CD4(+)
      and CD8(+) T cells were detected, while IL-10 was highly expressed by all three
      cell subpopulations. Taken together, these results show an evident imbalance
      between TNF-alpha and IFN-gamma that is unfavorable to amastigote replication
      control. Furthermore, L. shawi seems to regulate different cell populations to
      express deactivating cytokines to avoid its own destruction. This study indicates
      BALB/c mice as a potentially good experimental model for further studies on
      American cutaneous leishmaniosis caused by L. shawi.

PMID- 20060061
TI  - Cigarette smoking during pregnancy: chromosome translocations and phenotypic
      susceptibility in mothers and newborns.
AB  - The effects of maternal cigarette smoking during pregnancy on structural
      chromosome aberrations were evaluated in peripheral lymphocytes from 239 mothers
      and their 241 newborns to determine whether smoking during pregnancy, genetic
      susceptibility, and race are associated with chromosome aberrations including
      translocations. Demographic information and cigarette smoking data were obtained
      via questionnaire. There were 119 Caucasian Americans, 118 African Americans, and
      2 Asian Americans. The average maternal age was 24.9+/-5.8 (mean+/-S.D.) years.
      Thirty-nine percent of the Caucasian Americans and 45.4% of the African Americans
      self-reported that they were active smokers during the index pregnancy. The
      average number of cigarettes smoked per day was 2.65+/-5.75 and 1.37+/-3.17 for
      Caucasian and African American mothers, respectively. Peripheral blood
      lymphocytes from the mother and from the fetal side of the placenta were
      evaluated for chromosome aberrations by whole chromosome painting. Aliquots from
      the same blood samples were also used to assess genetic susceptibility with an in
      vitro bleomycin challenge assay. Spontaneous translocation frequencies in both
      maternal and newborn lymphocytes were not associated with cigarette smoking,
      socioeconomic status, or education. The absence of a smoking effect may be
      attributable to the low level of cigarette usage in these subjects. The average
      bleomycin-induced damage in the maternal and newborn populations was 0.37+/-0.27
      and 0.15+/-0.14 breaks per cell, respectively, a difference that was highly
      significant (p<0.0001). In newborns there was a positive association between
      bleomycin sensitivity and the frequencies of aberrations as measured by
      chromosome painting: p</=0.0007 for dicentrics and fragments, and p</=0.002 for
      translocations. Caucasian American newborns demonstrated a significant
      association between dicentrics and fragments as measured by painting, and
      bleomycin sensitivity (p</=0.0002), but no such association was observed for
      African American newborns. The results of this study indicate that while
      differences were observed between African Americans and Caucasian Americans, race
      does not appear to be a major contributor to chromosome damage in newborns or
      their mothers. However, peripheral lymphocytes in pregnant women are more
      susceptible to genetic damage than peripheral lymphocytes in newborns.

PMID- 20060063
TI  - Osteonecrosis and panniculitis as life-threatening signs.

PMID- 20060064
TI  - Increased incidence of small intestinal bacterial overgrowth during proton pump
      inhibitor therapy.
AB  - BACKGROUND & AIMS: Proton pump inhibitors (PPIs) can cause diarrhea, enteric
      infections, and alter the gastrointestinal bacterial population by suppressing
      the gastric acid barrier. Among patients that received long term PPI treatment,
      we evaluated the incidence of small intestinal bacterial overgrowth (SIBO;
      assessed by glucose hydrogen breath test [GHBT]), the risk factors for
      development of PPI-related SIBO and its clinical manifestations, and the
      eradication rate of SIBO after treatment with rifaximin. METHODS: GHBTs were
      given to 450 consecutive patients (200 with gastroesophageal reflux disease who
      received PPIs for a median of 36 months; 200 with irritable bowel syndrome [IBS],
      in absence of PPI treatment for at least 3 years; and 50 healthy control subjects
      that had not received PPI for at least 10 years). Each subject was given a
      symptoms questionnaire. RESULTS: SIBO was detected in 50% of patients using PPIs,
      24.5% of patients with IBS, and 6% of healthy control subjects; there was a
      statistically significant difference between patients using PPIs and those with
      IBS or healthy control subjects (P < .001). The prevalence of SIBO increased
      after 1 year of treatment with PPI. The eradication rate of SIBO was 87% in the
      PPI group and 91% in the IBS group. CONCLUSIONS: SIBO, assessed by GHBT, occurs
      significantly more frequently among long term PPI users than patients with IBS or
      control subjects. High dose therapy with rifaximin eradicated 87%-91% of cases of
      SIBO in patients who continued PPI therapy.

PMID- 20060065
TI  - Electronic images of the month. Duodenal ulceration following variceal
      embolization with coils and vascular plugs.

PMID- 20060066
TI  - Positive response to steroid therapy for autoimmune pancreatitis evaluated with
      fluorodeoxyglucose positron emission tomography.

PMID- 20060067
TI  - Electronic images of the month. An unusual presentation of hematemesis: a
      presentation of maxillary metastasis from hepatocellular carcinoma.

PMID- 20060068
TI  - Reflux is unlikely to occur during stable sleep.

PMID- 20060069
TI  - Gastric anisakiasis.

PMID- 20060070
TI  - Systematic review of the quality of patient information on the internet regarding
      inflammatory bowel disease treatments.
AB  - BACKGROUND & AIMS: Patients use the Internet as a resource for information about
      their diseases. A systematic review evaluating the quality of information
      available for inflammatory bowel disease patients on the Internet regarding
      treatment options was performed. METHODS: Google was used to identify 50 websites
      on 3 occasions. A data quality score (DQS) (potential score, 0-76) was developed
      to evaluate the content of websites that scores patient information on
      indications, efficacy, and side effects of treatment. Other outcome measures were
      a 5-point global quality score, a drug category quality score, the DISCERN
      instrument, a reading grade level score, and information about integrity.
      RESULTS: The median DQS was 22, range 0-74, median global quality score was 2.0,
      and median Flesch-Kincaid reading grade level was 12.0, range 6.9-13.7. Eight
      websites achieved a global quality score of 4 or 5. The DQS was highly associated
      with the global quality score (r = 0.82) and the DISCERN instrument (r = 0.89).
      There was poor association between the DQS and the rank order in all 3 Google
      searches. Information on funding source (59%) and date of last update (74%) were
      often lacking. CONCLUSIONS: There is marked variation in the quality of available
      patient information on websites about the treatment options for Crohn's disease
      and ulcerative colitis. Few websites provided high quality information. There is
      a need for high quality accredited websites that provide patient-oriented
      information on treatment options, and these sites need to be updated regularly.

PMID- 20060071
TI  - Gluten-free diet and steroid treatment are effective therapy for most patients
      with collagenous sprue.
AB  - BACKGROUND & AIMS: Collagenous sprue (CS) is characterized by the presence of a
      distinctive band of subepithelial collagen deposition in the small bowel. We
      evaluated the clinical characteristics, treatments, and outcomes of patients with
      CS. METHODS: Thirty patients with CS were identified at the 3 Mayo Clinic sites
      between 1993 and 2009. Clinical data from medical records were reviewed. RESULTS:
      The study cohort was 70% female (age range, 53-91 years). Most patients had
      severe diarrhea and weight loss. Hospitalization to treat dehydration was
      necessary in 16 (53%) patients. Associated immune-mediated diseases were noted in
      70% of the patients; celiac disease was the most frequent. Other associated
      diseases were microscopic colitis, hypothyroidism, and autoimmune enteropathy.
      The median thickness of the layer of subepithelial collagen deposition in the
      small bowel was 29 mum (20-56.5 mum). Subepithelial collagen deposition in the
      colon or stomach was noted in 8 patients. A clinical response was observed in 24
      (80%) patients after treatment with a combination of a gluten-free diet and
      immunosuppressive drugs. Histologic improvement was confirmed in 9 patients, with
      complete remission in 5. Two patients died (1 of complications of CS and 1 of
      another illness). CONCLUSIONS: Most patients with CS are treated effectively with
      a combination of gluten-free diet and steroids. CS is often associated with
      collagen deposition or chronic inflammation in other segments of the
      gastrointestinal tract as well as other immune-mediated disorders.

PMID- 20060072
TI  - Necrolytic migratory erythema due to glucagonoma.

PMID- 20060073
TI  - Time-dependent measure of a nanoscale force-pulse driven by the axonemal dynein
      motors in individual live sperm cells.
AB  - Nanoscale mechanical forces generated by motor proteins are crucial to normal
      cellular and organismal functioning. The ability to measure and exploit such
      forces is important to developing motile biomimetic nanodevices powered by
      biological motors for nanomedicine. Axonemal dynein motors positioned inside the
      sperm flagellum drive microtubule sliding and give rise to rhythmic beating. This
      force-generating action pushes the sperm cell through viscous media. Here we
      report new nanoscale information on how the propulsive force is generated by the
      sperm flagellum and how this force varies over time. Using a modified atomic
      force microscope, single-cell recordings reveal discrete approximately 50-ms
      pulses oscillating with amplitude 9.8 +/- 2.6 nN independent of pulse frequency
      (3.5-19.5 Hz). The average work carried out by each cell is 4.6 x 10(-16) J per
      pulse, equivalent to the hydrolysis of approximately 5500 molecules of adenosine
      triphosphate. The mechanochemical coupling at each active dynein head is
      approximately 2.2 pN per adenosine triphosphate molecule and approximately 3.9 pN
      per dynein arm. From the clinical editor: In this paper, nanoscale mechanical
      forces generated by axonemal dynein motors derived from sperm flagellum are
      examined and reported. These motor proteins are crucial to normal cellular and
      organismal functioning. The ability to measure and exploit such forces is
      important to developing motile biomimetic nanodevices powered by biological
      motors for nanomedicine.

PMID- 20060074
TI  - Doxorubicin-loaded solid lipid nanoparticles to overcome multidrug resistance in
      cancer therapy.
AB  - In the present study we developed doxorubicin-loaded solid lipid nanoparticles
      (SLN-Dox) using biocompatible compounds, assessed the in vitro hemolytic effect,
      and examined their in vivo effects on drug retention and apoptosis intensity in P
      glycoprotein-overexpressing MCF-7/ADR cells, a representative Dox-resistant
      breast cancer cell line. Our SLNs did not show hemolytic activity in human
      erythrocytes. In comparison with Dox, SLN-Dox efficiently enhanced apoptotic cell
      death through the higher accumulation of Dox in MCF-7/ADR cells. Therefore, SLN
      Dox have potential to serve as a useful therapeutic approach to overcome the
      chemoresistance of adriamycin-resistant breast cancer. FROM THE CLINICAL EDITOR:
      Doxorubicin loaded solid lipid nanoparticles (SLN-Dox) were studied in a cell
      line representative of doxorubicin resistant breast cancer. The nanoparticles did
      not show hemolytic activity; furthermore, they efficiently enhanced apoptotic
      cell death through higher accumulation of doxorubicin in cancer cells. This
      approach may be viable in overcoming the chemoresistance of adriamycin resistant
      breast cancer.

PMID- 20060075
TI  - Identification of deregulated genes by single wall carbon-nanotubes in human
      normal bronchial epithelial cells.
AB  - To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human
      normal lung cells, we compared the gene expression profiles of untreated human
      normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with
      SWCNTs. A complementary DNA microarray analysis consisting of 54,675 human genes
      revealed marked changes in the expression of 14,294 genes, with 7,029 genes being
      upregulated and 7,265 being downregulated. This comprehensive list of genes
      included those associated with cell cycle, apoptosis, cell survival, cell
      adhesion and motility, signal transduction, and transcription regulation.
      Additional analysis of 19 genes using reverse transcription-polymerase chain
      reaction confirmed the microarray analysis. More specifically, our study
      demonstrates to our knowledge for the first time, evidence that 9 of the 19 genes
      (most of which encode cell apoptotic, signal transduction, and transcription
      regulator products) are upregulated in the SWCNTs-treated HNBE cells as compared
      with untreated cells, whereas the remaining 10 of the 19 (involved in cell
      adhesion and motility, cell proliferation, and cell survival) are downregulated
      in SWCNTs-treated HNBE cells in comparison with untreated controls. These
      findings provide a large body of information regarding gene expression profiles
      associated with SWCNTs exposure in human lung bronchial epithelial cells, and
      also represent a source to investigate the mechanism of the effect of SWCNTs in
      human normal lung cells. From the clinical editor: In this study, the gene
      expression profile of human normal bronchial epithelial cells was compared with
      single-wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting
      of 54,675 human genes revealed significant changes in the expression of 14,294
      genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This
      serves as a first step in clarification of mechanisms of action and to
      investigate toxicity in this model.

PMID- 20060076
TI  - Results of laparoscopic cholecystectomy without energized dissection: a
      prospective study.
AB  - INTRODUCTION: Laparoscopic cholecystectomy (LC) a gold standard treatment of
      symptomatic gall stone disease has yet to become as safe as open cholecystectomy.
      The concerns of safety for both surgeon as well as patient are present even after
      the passage of "learning curve" phase. Emphasis on experience and technique have
      helped but for the morbidity associated with the use of energy sources. The
      purpose of this study was to evaluate the possibility of avoiding this morbidity
      by not using energy sources in LC. MATERIAL AND METHOD: Prospective case series,
      with a minimum follow up of 1 year. Consecutive, unselected patients of
      symptomatic gall stone disease operated by an experienced laparoscopic surgeon
      from July 2003-June 2005. Operative, early and late postoperative outcomes were
      evaluated. TECHNIQUE: LC was performed by dissecting in avascular Holy planes
      without using any energy source. RESULTS: LC could be performed safely in all 135
      patients. The technique was uniformly applicable irrespective of gender, age,
      time of presentation, grade of inflammation, adhesions or any comorbidity. There
      was no hemodynamic instability, conversion, injury manifesting early or late or
      any mortality. CONCLUSION: The potential injury from use of energy sources in LC
      can be avoided as it can be safely performed without using any energy source.

PMID- 20060077
TI  - Heterogeneity in thylakoid membrane proteome of Synechocystis 6803.
AB  - Cell-free extracts of Synechocystis 6803 were fractionated by successive
      ultracentrifugation at 40,000 x g, 90,000 x g and 150,000 x g to obtain the three
      thylakoid fractions designated as 40k, 90k and 150k fractions respectively. These
      fractions showed differences in absorption and emission spectra. Nano-LC-ESI-Q
      TOF MS analysis identified 123 proteins belonging to membrane as well as
      cytosolic fraction. Out of these proteins, there were 22 proteins with
      transmembrane helices and 12 proteins with signal peptide. There were 77 proteins
      common across all the three fractions. Most of these proteins were subunits of
      photosynthetic complexes, CF(0)-CF(1) ATP synthase or ribosomal proteins. Among
      the rest of the proteins, 8 were exclusive to 40k fraction, 3 were exclusive to
      90k fraction and 13 were exclusive to 150k fraction. There were 10 proteins
      common between 40k and 90k fractions and 12 proteins common between 90k and 150k
      fractions. There were no common proteins detected between 40k and 150 fractions.
      The results suggested existence of heterogeneity in thylakoids of Synechocystis
      6803, which may lead to micro-compartmentation and functional heterogeneity in
      the thylakoids of this organism as seen previously.

PMID- 20060078
TI  - Bone formation markers in patients with glucocorticoid-induced osteoporosis
      treated with teriparatide or alendronate.
AB  - Reduced osteoblast function is a primary defect in glucocorticoid-induced
      osteoporosis (GIO), and is reflected by decreased biochemical markers of bone
      formation, such as serum osteocalcin (OC) and procollagen type I N-terminal
      propeptide (PINP). This analysis compared the effects of teriparatide and
      alendronate on OC and PINP in patients with GIO. In a double-blind study, women
      (N=159) and men (N=38) with GIO were randomized to either teriparatide 20 mug/day
      by subcutaneous injection or to alendronate 10 mg/day orally. OC and PINP were
      measured in fasting-state serum samples obtained at baseline and at 1, 6, 18, and
      36 months. Baseline bone formation markers were below the reference interval
      (low) in 33% of patients for OC and in 4% of patients for PINP. On teriparatide
      therapy, the median OC and PINP levels increased by 92% and 108%, respectively,
      and this resulted in only 12% and 1% of patients being low at 6 months. On
      alendronate therapy, the median OC and PINP levels decreased by 40% and 53%,
      respectively, and this resulted in 68% and 34% of patients being low at 6 months.
      We conclude that bone formation as determined by surrogate markers was increased
      in teriparatide-treated patients with GIO and decreased in alendronate-treated
      patients with GIO.

PMID- 20060079
TI  - Relationship of total body fat mass to weight-bearing bone volumetric density,
      geometry, and strength in young girls.
AB  - Understanding the influence of total body fat mass (TBFM) on bone during the peri
      pubertal years is critical for the development of future interventions aimed at
      improving bone strength and reducing fracture risk. Thus, we evaluated the
      relationship of TBFM to volumetric bone mineral density (vBMD), geometry, and
      strength at metaphyseal and diaphyseal sites of the femur and tibia of young
      girls. Data from 396 girls aged 8-13 years from the "Jump-In: Building Better
      Bones" study were analyzed. Bone parameters were assessed using peripheral
      quantitative computed tomography (pQCT) at the 4% and 20% distal femur and 4% and
      66% distal tibia of the non-dominant leg. Bone parameters at the 4% sites
      included trabecular vBMD, periosteal circumference, and bone strength index
      (BSI), while at the 20% femur and 66% tibia, parameters included cortical vBMD,
      periosteal circumference, and strength-strain index (SSI). Multiple linear
      regression analyses were used to assess associations between bone parameters and
      TBFM, controlling for muscle cross-sectional area (MCSA). Regression analyses
      were then repeated with maturity, bone length, physical activity, and ethnicity
      as additional covariates. Analysis of covariance (ANCOVA) was used to compare
      bone parameters among tertiles of TBFM. In regression models with TBFM and MCSA,
      associations between TBFM and bone parameters at all sites were not significant.
      TBFM explained very little variance in all bone parameters (0.2-2.3%). In
      contrast, MCSA was strongly related (p<0.001) to all bone parameters, except
      cortical vBMD. The addition of maturity, bone length, physical activity, and
      ethnicity did not alter the relationship between TBFM and bone parameters. With
      bone parameters expressed relative to total body mass, ANCOVA showed that all
      outcomes were significantly (p<0.001) greater in the lowest compared to the
      middle and highest tertiles of TBFM. Although TBFM is correlated with femur and
      tibia vBMD, periosteal circumference, and strength in young girls, this
      relationship is significantly attenuated after adjustment for MCSA. Nevertheless,
      girls with higher TBFM relative to body mass have markedly diminished vBMD,
      geometry, and bone strength at metaphyseal and diaphyseal sites of the femur and
      tibia.

PMID- 20060080
TI  - Psychotropic drugs have contrasting skeletal effects that are independent of
      their effects on physical activity levels.
AB  - Popular psychotropic drugs, like the antidepressant selective serotonin reuptake
      inhibitors (SSRIs) and tricyclic antidepressants (TCAs), and the mood stabilizer
      lithium, may have skeletal effects. In particular, preclinical observations
      suggest a direct negative effect of SSRIs on the skeleton. A potential caveat in
      studies of the skeletal effects of psychotropic drugs is the hypoactive (skeletal
      unloading) phenotype they induce. The aim of this study was to investigate the
      contribution of physical inactivity to the skeletal effects of psychotropic drugs
      by studying bone changes in cage control and tail suspended mice treated with
      either vehicle, SSRI, TCA or lithium. Tail suspension was used to control for
      drug differences on physical activity levels by normalizing skeletal loading
      between groups. The psychotropic drugs were found to have contrasting skeletal
      effects which were independent of drug effects on animal physical activity
      levels. The latter was evident by an absence of statistical interactions between
      the activity and drug groups. Pharmacological inhibition of the 5
      hydroxytryptamine (5-HT) transporter (5-HTT) using a SSRI reduced in vivo gains
      in lower extremity BMD, and negatively altered ex vivo measures of femoral and
      spinal bone density, architecture and mechanical properties. These effects were
      mediated by a decrease in bone formation without a change in bone resorption
      suggesting that the SSRI had anti-anabolic skeletal effects. In contrast,
      glycogen synthase kinase-3[beta] (GSK-3[beta]) inhibition using lithium had
      anabolic effects improving in vivo gains in BMD via an increase in bone
      formation, while TCA-mediated inhibition of the norepinephrine transporter had
      minimal skeletal effect. The observed negative skeletal effect of 5-HTT
      inhibition, combined with recent findings of direct and indirect effects of 5-HT
      on bone formation, are of interest given the frequent prescription of SSRIs for
      the treatment of depression and other affective disorders. Likewise, the anabolic
      effect of GSK-3[beta] inhibition using lithium reconfirms the importance of
      Wnt/beta-catenin signaling in the skeleton and it's targeting by recent drug
      discovery efforts. In conclusion, the current study demonstrates that different
      psychotropic drugs with differing underlying mechanisms of action have
      contrasting skeletal effects and that these effects do not result indirectly via
      the generation of animal physical inactivity.

PMID- 20060082
TI  - Efficacy and safety of monthly ibandronate in men with low bone density.
AB  - INTRODUCTION: Monthly oral ibandronate is indicated for the prevention and
      treatment of osteoporosis in postmenopausal women. The STudy Researching
      Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg
      monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related
      low bone density. METHODS: STRONG was a 1-year, placebo-controlled, randomized (2
      ibandronate: 1 placebo), double-blind study that enrolled ambulatory men aged >
      or =30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores
      < or =-2.0 and lumbar spine (LS) BMD T-scores < or =-1.0 or LS BMD T-scores < or
      =-2.0, FN BMD T-scores < or =-1.0, and BMD T-scores > or =-4.0 at any site
      assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean
      percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT]
      population). Secondary endpoints included mean BMD changes from baseline at the
      FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers
      (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of
      type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline
      phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day)
      and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared
      using analysis of covariance with treatment, investigative site, and baseline
      testosterone as factors and baseline BMD as a covariate. RESULTS: The ITT
      population consisted of 132 men; 47 received placebo and 85 received monthly
      ibandronate. Men who received ibandronate achieved greater increases in LS BMD at
      12 months than those who received placebo (3.5% vs. 0.9%, respectively;
      difference, 2.6; p<0.001). The ibandronate group also achieved greater 12-month
      BMD increases than the placebo group, respectively, at the TH (1.8% vs. -0.3%;
      difference, 2.1; p<0.001), FN (1.2% vs. -0.2%; difference, 1.4; p=0.012), and TR
      (2.2% vs. 0.4%; difference, 1.7; p<0.005). In men who completed the study and
      adhered to the protocol (per-protocol (PP) population), percent decreases in
      median sCTX and BSAP levels from baseline were also greater with ibandronate
      versus placebo (p< or =0.001 for both comparisons). Overall, monthly ibandronate
      was well tolerated. CONCLUSIONS: In men with low BMD, 1 year of treatment with
      oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and
      hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and
      was generally well tolerated.

PMID- 20060083
TI  - Universal rubella vaccination programme and maternal rubella immune status: a
      tale of two systems.
AB  - Maternal rubella status was compared between local residents with non-residents
      who delivered in our hospital during 1998-2008. Among the 60,822 women, non
      immunity was more common in the non-residents (19.9% versus 8.1%, P<0.001).
      Significant difference and positive correlation with age and parity were found
      for both groups, but a significant inverse correlation with year-of-birth was
      found only in the residents. Regression analysis confirmed that birth after 1970
      was associated with reduced odds of non-immunity, which indicated that the
      rubella vaccination programme, introduced since 1978, has succeeded in reducing
      the incidence of non-immunity to <5% in the youngest generation.

PMID- 20060081
TI  - Correlations between biochemical markers of bone turnover and bone density
      responses in patients with glucocorticoid-induced osteoporosis treated with
      teriparatide or alendronate.
AB  - The purpose of this post hoc analysis was to determine whether baseline
      concentrations or early changes in serum bone turnover markers were correlated
      with changes in bone mineral density (BMD) at 18 months in patients with
      glucocorticoid-induced osteoporosis (GIO) treated with teriparatide (n=80; 20
      mug/day) or alendronate (n=77; 10 mg/day). Bone markers included type I collagen
      N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), bone
      alkaline phosphatase (bone ALP), and cross-linked C-telopeptide of type I
      collagen (Sbeta-CTX). The relationship between baseline and early changes in
      markers and the 18-month changes in lumbar spine (LS) and femoral neck (FN) BMD
      was evaluated using Spearman correlation analysis. In the teriparatide group,
      increases in LS and FN BMD at 18 months were not significantly correlated with
      baseline marker concentrations (P>0.05) but were correlated with the increases in
      PINP at 1 and 6 months (P<0.05). In the alendronate group, the increase in FN BMD
      at 18 months was positively correlated with baseline marker concentrations
      (P<0.05) and negatively correlated with change in PINP and Sbeta-CTX at 1 and 6
      months. In addition, in the alendronate group, the increase in LS BMD was
      negatively correlated with change in Sbeta-CTX at 1 month (P<0.05). Increases in
      BMD at the spine and hip were independent of baseline bone turnover in the
      teriparatide group, while increases in hip BMD were dependent on baseline bone
      turnover in the alendronate group. With both therapies, early changes in some
      bone turnover markers were correlated with 18-month gains in BMD in patients with
      GIO.

PMID- 20060084
TI  - Lymphadenitis caused by H1N1 vaccination: case report.
AB  - A patient admitted to hospital for a supraclavicular painful mass.
      Ultrasonography showed soliter lymphadenopathy. He underwent H1N1 vaccination 1
      week before this lymphadenopathy developed. Groosly the mass measured
      1cmx0.8cmx0.8cm. It was round, yellow to brown, slightly soft. In pathologic
      examination, we detected edema in capsule of lymph node. The basic architecture
      was preserved. There was mottled appearance caused by marked proliferation of
      immunoblasts which were positive with CD 30. Also large, unusual immunoblasts
      which closely resemble mononuclear hodgkin cells were present. These unusual
      immunoblasts were positive with CD 30, too. For differential diagnosis, at first
      we should regard hodgkin lymphoma. We suggested that lymphadenitis may be a side
      effect of H1N1 vaccination.

PMID- 20060085
TI  - Sensitivity and specificity of BCG scar reading among HIV-infected children.
AB  - BCG scar has been used as an indicator of vaccination with BCG in the past, but
      the validity of scar among HIV-positive children is still unknown. The validity
      of BCG scar reading among such children was estimated, using three different gold
      standards. The sensitivity ranged from 81.3% (95%-CI: 78.0-84.2) to 91.6% (95%
      CI: 88.4-94.0), when the gold standards were, respectively, information from the
      adult responsible for the child and the vaccination card. The specificity ranged
      from 90.5% (95% CI: 81.6-95.5) to 94.1% (95% CI: 87.7-97.4), when the gold
      standards were, respectively, the vaccination card and information from the adult
      responsible for the child. Reading of BCG scar was shown to be a good indicator
      for vaccination in the past, among HIV-infected children.

PMID- 20060086
TI  - Cross-cultural adaptation and validation of the French version of the Hip
      disability and Osteoarthritis Outcome Score (HOOS) in hip osteoarthritis
      patients.
AB  - OBJECTIVE: To translate and adapt the Hip disability and Osteoarthritis Outcome
      Score (HOOS) into French and to evaluate the psychometric properties of this new
      version, by testing feasibility, internal consistency, construct validity,
      reliability and responsiveness, in patients with hip osteoarthritis (OA).
      METHODS: The French version of the HOOS was developed according to published
      international guidelines to ensure content validity. The new version was then
      evaluated in two symptomatic hip OA populations, one with no indication for joint
      replacement (medical group), and the other waiting for total hip replacement
      (THR) (surgery group). The psychometric properties assessed were feasibility:
      percentage of responses, floor and ceiling effects; internal consistency using
      Cronbach's alpha; construct validity by evaluating correlations with the
      Lequesne's index and the visual analogic scale (VAS) for pain (Pearson's
      correlation coefficient); reliability: intra-class correlation coefficient (ICC),
      Bland et Altman representation; responsiveness by comparing the results of before
      and 1 month after injection of hyaluronic acid (medical group) and by comparing
      the pre and 3 months post THR results (surgery group) by calculating standardized
      response mean (SRM) and effect size (ES). RESULTS: A total of 88 patients were
      recruited; 58 in the medicine group (mean age=61.8+/-9 years, range 42-81, 70%
      women) and 30 in the surgery group (mean age=67.5+/-9 years, range 50-81, 68%
      women). The percentage of item responses was excellent (99%). Neither a floor nor
      a ceiling effect was observed, except for a ceiling effect (17.8% of patients
      with worst possible score) observed prior to surgery in the sport and recreation
      subscale. The internal consistency was good for four of the five HOOS subscales.
      As expected, the strongest correlations were observed between all HOOS subscales
      and Lequesne's index or VAS pain, indicating good construct validity. The
      reliability was good, with an ICC>0.8 for all subscales. The responsiveness was
      good for all domains 1 month after hyaluronic acid injection (ES ranging from
      0.73 to 1.86 and SRM from 0.51 to 1.04) and high for all domains 3 months after
      THR (ES ranging from 1.47 to 2.08 and SRM ranging from 1.97 to 3.24). CONCLUSION:
      The French version of HOOS demonstrated good psychometric properties and appears
      to be useful for the evaluation of patient-relevant outcome whatever the severity
      of hip OA. This study provides a basis for the use of this French version of the
      HOOS in future clinical trials.

PMID- 20060087
TI  - Functional gene group analysis reveals a role of synaptic heterotrimeric G
      proteins in cognitive ability.
AB  - Although cognitive ability is a highly heritable complex trait, only a few genes
      have been identified, explaining relatively low proportions of the observed trait
      variation. This implies that hundreds of genes of small effect may be of
      importance for cognitive ability. We applied an innovative method in which we
      tested for the effect of groups of genes defined according to cellular function
      (functional gene group analysis). Using an initial sample of 627 subjects, this
      functional gene group analysis detected that synaptic heterotrimeric guanine
      nucleotide binding proteins (G proteins) play an important role in cognitive
      ability (P(EMP) = 1.9 x 10(-4)). The association with heterotrimeric G proteins
      was validated in an independent population sample of 1507 subjects.
      Heterotrimeric G proteins are central relay factors between the activation of
      plasma membrane receptors by extracellular ligands and the cellular responses
      that these induce, and they can be considered a point of convergence, or a
      "signaling bottleneck." Although alterations in synaptic signaling processes may
      not be the exclusive explanation for the association of heterotrimeric G proteins
      with cognitive ability, such alterations may prominently affect the properties of
      neuronal networks in the brain in such a manner that impaired cognitive ability
      and lower intelligence are observed. The reported association of synaptic
      heterotrimeric G proteins with cognitive ability clearly points to a new
      direction in the study of the genetic basis of cognitive ability.

PMID- 20060088
TI  - Turning placenta into brain: placental mesenchymal stem cells differentiate into
      neurons and oligodendrocytes.
AB  - OBJECTIVE: We aimed to induce neural stem (NSC) and progenitor cells (NPC) from
      human placental tissues. STUDY DESIGN: Placental stem cells from first-trimester
      placental chorionic villi and term chorion were isolated. Neural differentiation
      was initiated with plating on collagen, retinoic acid, and/or human brain-derived
      neurotrophic factor and epidermal and fibroblast growth factor. Differentiation
      into neurons, oligodendrocytes, and astrocytes was monitored by
      immunohistochemistry. Two-dimensional polyacrylamide gel electrophoresis, high
      performance liquid chromatography, and tandem mass spectrometry were used to
      identify proteins involved in the differentiation. RESULTS: Differentiated cells
      were mostly immediately postmitotic with some more but not fully mature
      postmitotic neurons. Neurons had dopaminergic or serotonergic character. Some
      cells differentiated into predominantly immature oligodendrocytes. Upon
      differentiation, neuron-specific proteins were up-regulated, whereas placental
      proteins were reduced. CONCLUSION: Stem cells derived from human placenta can be
      differentiated into neural progenitors.

PMID- 20060089
TI  - Health-related quality of life and patient satisfaction after global endometrial
      ablation for menorrhagia in women with bleeding disorders: a follow-up survey and
      systematic review.
AB  - OBJECTIVE: The purpose of this study was to describe health-related quality of
      life and satisfaction after global endometrial ablation in women with bleeding
      disorders and a systematic review of the literature. STUDY DESIGN: A follow-up
      survey was mailed to 36 patients with bleeding disorders and 110 reference
      patients (no coagulopathies) who underwent global endometrial ablation for
      menorrhagia. The survey included a generic (SF-12) and menorrhagia multi
      attribute utility scale questionnaires. RESULTS: Ninety-six women (66%)
      responded. The total menorrhagia multiattribute utility scale score increased
      from 35-100 in bleeding disorder cohort (P = .03) and from 48-100 in the
      reference cohort (P < .001). Although postablation SF-12 mental domain scores
      were comparable in both cohorts (55 vs 55; P = .67), physical domain scores were
      lower in the bleeding disorder cohort (50 vs 56; P < .001). High satisfaction was
      reported by both cohorts (95% vs 84%; P = .60). CONCLUSION: Global endometrial
      ablation improved health-related quality of life for women with bleeding
      disorders and had high satisfaction rates.

PMID- 20060090
TI  - Comparison of adnexal torsion between pregnant and nonpregnant women.
AB  - OBJECTIVE: The purpose of this study was to compare clinical manifestations,
      treatment, and pregnancy outcome of adnexal torsion in pregnant and nonpregnant
      women. STUDY DESIGN: We conducted a retrospective case-control study in the
      Departments of Gynecology at 2 tertiary centers between 1999-2008. Forty-one
      pregnant and 77 nonpregnant women with surgically proved adnexal torsion were
      assessed. RESULTS: Recurrence rate of torsion was 19.5% in pregnant women and
      9.1% in control subjects; 73% of pregnant women conceived through assisted
      reproductive technologies. Doppler blood flow was falsely normal in 61% of
      pregnant women and in 45% of nonpregnant women; 83.3% of pregnant women delivered
      at term. Laparoscopic detorsion was the main surgical procedure. CONCLUSION:
      Presentation of adnexal torsion is similar in pregnant and nonpregnant women.
      Past assisted reproductive technology is an important risk factor in pregnancy.
      Doppler blood flow has a high false-negative rate and should not outweigh
      clinical suspicion. Although pregnancy outcome is favorable, the high rate of
      recurrence raises the issue of surgical fixation at the first episode.

PMID- 20060091
TI  - Human cytomegalovirus reinfection is associated with intrauterine transmission in
      a highly cytomegalovirus-immune maternal population.
AB  - OBJECTIVE: To determine contribution of reinfection with new strains of
      cytomegalovirus in cytomegalovirus seromimmune women to incidence of congenital
      cytomegalovirus infection. STUDY DESIGN: In 7848 women studied prospectively for
      congenital cytomegalovirus infection from a population with near universal
      cytomegalovirus seroimmunity, sera from 40 mothers of congenitally infected
      infants and 109 mothers of uninfected newborns were analyzed for strain-specific
      anticytomegalovirus antibodies. RESULTS: All women were cytomegalovirus
      seroimmune at first prenatal visit. Reactivity for 2 cytomegalovirus strains was
      found in 14 of 40 study mothers and in 17 of 109 control mothers at first
      prenatal visit (P = .009). Seven of 40 (17.5%) study women and 5 of 109 (4.6%)
      controls (P = .002) acquired antibodies reactive with new cytomegalovirus strains
      during pregnancy. Evidence of infection with more than 1 strain of
      cytomegalovirus before or during current pregnancy occurred in 21 of 40 study
      mothers and 22 of 109 controls (P < .0001). CONCLUSION: Maternal reinfection by
      new strains of cytomegalovirus is a major source of congenital infection in this
      population.

PMID- 20060092
TI  - Prenatal diagnosis and outcome of isolated interrupted inferior vena cava.
AB  - OBJECTIVE: Report our experience in prenatal diagnosis of 11 cases of interrupted
      inferior vena cava, summarize the clinical significance and implications of this
      variant. STUDY DESIGN: Retrospective analysis of 11 fetuses diagnosed with
      interrupted inferior vena cava, of 55,457 pregnant women who underwent extensive
      fetal anomaly scan during 20 years. RESULTS: Eight of the 11 fetuses with
      interrupted inferior vena cava had a completely normal outcome. One had also
      normal outcome but abnormal function of the spleen. One had multiple
      abnormalities, and 1 case was lost to follow up. CONCLUSION: The incidence of
      IIVC is 1:5000. In the vast majority (90%) of the cases, it is an isolated
      variant not associated with isomerism or fetal anomalies. In all the cases of
      isolated interrupted inferior vena cava, the outcome is favorable. In 10% of
      isolated interrupted inferior vena cava, abnormal function of the spleen may be
      detected after delivery, necessitating antipneumococcal vaccination.

PMID- 20060093
TI  - Prophylactic bilateral oophorectomy or removal of remaining ovary at the time of
      hysterectomy in the United States, 1979-2004.
AB  - OBJECTIVE: The purpose of this study was to describe national rates and trends of
      prophylactic bilateral oophorectomy or remaining oophorectomy (BO/RO) at
      hysterectomy in women without specific gynecologic disease. STUDY DESIGN: Data
      from the National Hospital Discharge Survey were analyzed for 1979-2004.
      Hysterectomies were divided into 2 groups: (1) hysterectomy with BO/RO and (2)
      hysterectomy alone (> or =1 ovary remaining). Age-adjusted rates (AARs) were
      calculated with 2000 US census data. RESULTS: Approximately 3,686,000
      hysterectomies with BO/RO were performed from 1979-2004. AARs of hysterectomy
      with BO/RO decreased during this period; the AARs in women > or =50 years old
      increased. The number of hysterectomies alone was 5,461,100, and AARs of
      hysterectomy alone decreased significantly from 2.9 per 1000 women in from 1979
      1981 to 1.1 per 1000 women in 2001 (P < .001). The proportion of women who
      underwent hysterectomy with BO/RO increased from 29% in 1979 to 45% in 2004.
      CONCLUSION: Although AARs of prophylactic BO/RO decreased from 1979-2004, the
      actual proportion of BO/RO at hysterectomy increased.

PMID- 20060094
TI  - Tissue tumor marker expression in smokers, including serum cotinine
      concentrations, in women with cervical intraepithelial neoplasia or normal
      squamous cervical epithelium.
AB  - OBJECTIVE: The purpose of this study was to investigate correlations between
      smoking and serum cotinine, respectively, and tumor marker expression in cervical
      intraepithelial neoplasia (CIN) and normal epithelium. STUDY DESIGN: Women (n =
      228) with cervical biopsy specimens that ranged histologically from normal to
      carcinoma in situ (CIN III) were included. Expression of 11 tumor markers with
      possible relevance in cervical neoplasms was studied. Smoking habits were
      recorded, and serum was assessed for cotinine concentrations. RESULTS: No
      differences were found in tumor marker expression in normal epithelium between
      smokers and nonsmokers. The tumor suppressors p53 and fragile histidine triad and
      the immunologic marker interleukin-10 were underexpressed, and the tumor markers
      cyclooxygenase-2 and Ki-67 were overexpressed in smoking, compared with
      nonsmoking, women with CIN and particularly in all fertile women. CONCLUSION: The
      molecular pattern indicates that smoking exerts unfavorable effects in cervical
      neoplasia. This provides biologic evidence of smoking being a true cofactor in
      cervical neoplasia.

PMID- 20060095
TI  - Amniocentesis and chorionic villus sampling in twin gestations: which is the best
      sampling technique?
AB  - OBJECTIVE: To compare the fetal loss rate <24 weeks and the preterm premature
      rupture of the membranes <34 weeks' gestation according to type of invasive
      procedure and to sampling techniques in twins. STUDY DESIGN: Retrospective cohort
      study of 204 twin pregnancies, who underwent amniocentesis (100) or chorionic
      villus sampling (104). RESULTS: Fetal loss rate <4 weeks was 3.85% in chorionic
      villus sampling group and 4.00% in amniocentesis group (P value not significant).
      According to sampling technique, fetal loss rate was 4.17% (chorionic villus
      sampling 1 puncture), 2.70% (amniocentesis 1 puncture), 3.75% (chorionic villus
      sampling 2 punctures), and 4.76% (amniocentesis 2 punctures), (P values not
      significant). Preterm premature rupture of the membranes rate <34 weeks was 8.2%
      chorionic villus sampling group and 10% in amniocentesis group (P value not
      significant). According to sampling technique, preterm premature rupture of the
      membranes rate was 12.5% (chorionic villus sampling 1 puncture), 8.1%
      (amniocentesis 1 puncture), 6.9% (chorionic villus sampling 2 punctures), and
      11.1 % (amniocentesis 2 punctures), (P values not significant). CONCLUSION:
      Double entry technique does not affect significantly the outcomes evaluated, in
      both amniocentesis and chorionic villus sampling.

PMID- 20060096
TI  - The effect of load distribution within military load carriage systems on the
      kinetics of human gait.
AB  - Military personnel carry their equipment in load carriage systems (LCS) which
      consists of webbing and a Bergen (aka backpack). In scientific terms it is most
      efficient to carry load as close to the body's centre of mass (CoM) as possible,
      this has been shown extensively with physiological studies. However, less is
      known regarding the kinetic effects of load distribution. Twelve experienced load
      carriers carried four different loads (8, 16, 24 and 32 kg) in three LCS
      (backpack, standard and AirMesh). The three LCS represented a gradual shift to a
      more even load distribution around the CoM. Results from the study suggest that
      shifting the CoM posteriorly by carrying load solely in a backpack significantly
      reduced the force produced at toe-off, whilst also decreasing stance time at the
      heavier loads. Conversely, distributing load evenly on the trunk significantly
      decreased the maximum braking force by 10%. No other interactions between LCS and
      kinetic parameters were observed. Despite this important findings were
      established, in particular the effect of heavy load carriage on maximum braking
      force. Although the total load carried is the major cause of changes to gait
      patterns, the scientific testing of, and development of, future LCS can modify
      these risks.

PMID- 20060097
TI  - Attentional bias towards angry faces in childhood anxiety disorders.
AB  - OBJECTIVE: To examine attentional bias towards angry and happy faces in 8-12 year
      old children with anxiety disorders (n=29) and non-anxious controls (n=24).
      METHOD: Children completed a visual-probe task in which pairs of angry/neutral
      and happy/neutral faces were displayed for 500ms and were replaced by a visual
      probe in the spatial location of one of the faces. RESULTS: Children with more
      severe anxiety showed an attentional bias towards angry relative to neutral
      faces, compared with anxious children who had milder anxiety and non-anxious
      control children, both of whom did not show an attentional bias for angry faces.
      Unexpectedly, all groups showed an attentional bias towards happy faces relative
      to neutral ones. CONCLUSIONS: Anxiety symptom severity increases attention to
      threat stimuli in anxious children. This association may be due to differing
      threat appraisal processes or emotion regulation strategies.

PMID- 20060098
TI  - Future-oriented decision-making in Generalized Anxiety Disorder is evident across
      different versions of the Iowa Gambling Task.
AB  - Generalized Anxiety Disorder (GAD) and excessive worrying are characterized by a
      preoccupation with the future. Thus, enhanced identification of potential future
      punishments or omissions of reward may be related to the disorder. To test this
      hypothesis, n=47 students meeting GAD criteria according to the GADQ-IV (GAD
      analogues) or not (control participants) performed the Iowa Gambling Task, which
      has been related to sensitivity to future consequences. In order to disentangle
      sensitivity to future loss and sensitivity to high short-term loss magnitudes,
      which could also lead to enhanced Iowa Gambling Task performance, participants
      also performed a modified version of the task with reversed contingencies. In
      both versions, GAD analogues learned to avoid decisions with high probability of
      long-term loss significantly faster than control participants. Results,
      therefore, indicate that GAD is characterized by enhanced processing of potential
      future losses rather than sensitivity to large short-term loss.

PMID- 20060099
TI  - A CTL-based liposomal vaccine capable of inducing protection against
      heterosubtypic influenza viruses in HLA-A*0201 transgenic mice.
AB  - The current vaccination strategy against influenza is to induce the production of
      antibodies directed against surface antigens of viruses. However, the frequent
      changes in the surface antigens of influenza viruses allow the viruses to avoid
      antibody-mediated immunity. On the other hand, it is known that cytotoxic T
      lymphocyte (CTL) populations directed against internal antigens of influenza A
      virus are broadly cross-reactive to influenza virus subtypes. In the present
      study, liposomal conjugates with CTL epitope peptides derived from highly
      conserved internal antigens of influenza viruses were evaluated for their ability
      to protect against infection with influenza viruses. Liposomal conjugates with
      peptide M1 58-66, an HLA-A*0201-binding CTL epitope present within the amino-acid
      sequence of the M1 coding region, successfully induced antigen-specific CD8(+) T
      cells and CTLs in HLA-A*0201-transgenic mice. Moreover, after nasal infection
      with either the H1N1 or H3N2 virus, viral replication in the lung was
      significantly inhibited in the immunized mice. These protective activities lasted
      at least 6months after the immunization. Thus, these results suggest that
      liposome-coupled CTL epitope peptides derived from highly conserved internal
      antigens of influenza viruses might be applicable to the development of vaccines
      that induce protection against infection with heterosubtypic influenza viruses.

PMID- 20060100
TI  - Functional disconnection of frontal cortex and visual cortex in attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Current pathophysiologic models of attention-deficit/hyperactivity
      disorder (ADHD) suggest that impaired functional connectivity within brain
      attention networks may contribute to the disorder. In this
      electroencephalographic (EEG) study, we analyzed cross-frequency amplitude
      correlations to investigate differences in cue-induced functional connectivity in
      typically developing children and children with ADHD. METHODS:
      Electroencephalographic activity was recorded in 25 children aged 8 to 12 years
      (14 with ADHD) while they performed a cross-modal attention task in which cues
      signaled the most likely (.75 probability) modality of an upcoming target. The
      power spectra of the EEG in the theta (3-5 Hz) and alpha (8-12 Hz) bands were
      calculated for the 1-sec interval after the cue and before the target while
      subjects prepared to discriminate the expected target. RESULTS: Both groups
      showed behavioral benefits of the predictive attentional cues, being faster and
      more accurate for validly cued targets (e.g., visual target preceded by a cue
      predicting a visual target) than to invalidly cued targets (e.g., visual target
      preceded by a cue predicting an auditory target); in addition, independent of cue
      target validity, typical children were faster to respond overall. In the
      typically developing children, the alpha activity was differentially modulated by
      the two cues and anticorrelated with midfrontal theta activity; these EEG
      correlates of attentional control were not observed in the children with ADHD.
      CONCLUSIONS: Our findings provide neurophysiological evidence for a specific
      deficit in top-down attentional control in children with ADHD that is manifested
      as a functional disconnection between frontal and occipital cortex.

PMID- 20060102
TI  - Oxytocin: prosocial behavior, social salience, or approach-related behavior?

PMID- 20060103
TI  - Auditory hallucinations in schizophrenia are associated with reduced functional
      connectivity of the temporo-parietal area.
AB  - BACKGROUND: Schizophrenia has been conceptualized as a disorder of integration of
      neural activity across distributed networks. However, the relationship between
      specific symptom dimensions and patterns of functional connectivity remains
      unclear. The current study aimed to investigate the relationship between auditory
      verbal hallucinations (AVH), a particularly prevalent and clinically relevant
      symptom in schizophrenia, and functional connectivity of the temporo-parietal
      junction (TPJ). METHODS: Resting state functional magnetic resonance imaging
      scans were obtained from 27 schizophrenia patients with AVH and 27 matched
      control subjects. We calculated correlations reflecting functional connectivity
      between a priori defined regions-of-interest and the bilateral TPJ seed regions,
      comprising the neural network involved in inner speech processes and AVH.
      RESULTS: Compared with healthy control subjects, schizophrenia patients showed
      reduced functional connectivity between left TPJ and the right homotope of Broca.
      Within the patient group, more severe AVH were associated with reduced neural
      coupling between left TPJ and bilateral anterior cingulate as well as the
      bilateral amygdala. CONCLUSIONS: In schizophrenia patients with chronic
      hallucinations, the left TPJ-a critical node in the speech perception/AVH network
      shows reduced functional connectivity with brain areas involved in the
      attribution of agency, self-referent processing, and attentional control.

PMID- 20060105
TI  - Repetitive transcranial magnetic stimulation reduces cue-induced food craving in
      bulimic disorders.
AB  - BACKGROUND: Craving or the "urge to consume" is a characteristic of bulimic
      eating disorders and addictions. Dysfunction of the dorsolateral prefrontal
      cortex (DLPFC) is associated with craving. We investigated whether stimulation of
      the DLPFC reduces food craving in people with a bulimic-type eating disorder.
      METHODS: Thirty-eight people with bulimic-type eating disorders were randomly
      allocated to receive one session of real or sham high-frequency repetitive
      transcranial magnetic stimulation (rTMS) to the left DLPFC in a double-blind
      procedure. Outcome measures included self-reported food craving immediately after
      the stimulation session and frequency of bingeing over a 24-hour follow-up
      period. RESULTS: Compared with sham control, real rTMS was associated with
      decreased self-reported urge to eat and fewer binge-eating episodes over the 24
      hours following stimulation. CONCLUSIONS: High-frequency rTMS of the left DLPFC
      lowers cue-induced food cravings in people with a bulimic eating disorder and may
      reduce binge eating. These results provide a rationale for exploring rTMS as a
      treatment for bulimic eating disorders.

PMID- 20060106
TI  - Deuterium effect on ionization and fragmentation patterns of monosaccharides
      ionized by atmospheric pressure chemical ionization.
AB  - Glucose, galactose, and mannose in H(2)O and D(2)O were ionized by an atmospheric
      pressure chemical ionization (APCI) method. Isotope effects on fragmentation
      patterns of the monosaccharides were examined by deuterium replacement of the -OH
      groups to distinguish the isomers with a single mass spectrometer. The most
      abundant ions were the [M+H(2)O](+)() and [M(D5)+D+D(2)O](+) for using H(2)O and
      D(2)O as solvent and eluent, respectively. Major fragment ions were the [M-OH](+)
      and [M-OH-H(2)O](+) in H(2)O, while those in D(2)O were the [M(D5)+D-D(2)O](+)
      and [M(D5)+D-2D(2)O](+). The differences in the product ions generated in H(2)O
      and D(2)O were due to enhancement of the strength of hydrogen bonding by the
      deuterium replacement. Variations of the ion intensity ratios of the [M-OH](+)/[M
      OH-H(2)O](+) and [M(D5)-OD](+)/[M(D5)-OD-D(2)O](+) with the fragmentor voltage
      showed different trends depending on the kind of monosaccharides. By comparing
      the ion intensity ratios of the [M+H(2)O](+)()/M(+)(),
      [M(D5)+D+D(2)O](+)/[M(D5)+D](+), [M-OH](+)/[M-OH-H(2)O](+), and [M(D5)+D
      D(2)O](+)/[M(D5)+D-2D(2)O](+), it was possible to distinguish the isomers of
      monosaccharides.

PMID- 20060104
TI  - Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release
      plays a key role in alcohol dependence.
AB  - BACKGROUND: Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid
      (GABA)ergic systems in the central amygdala (CeA) are implicated in the high
      anxiety, high-drinking profile associated with ethanol dependence. Ethanol
      augments CeA GABA release in ethanol-naive rats and mice. METHODS: Using naive
      and ethanol-dependent rats, we compared electrophysiologic effects and
      interactions of CRF and ethanol on CeA GABAergic transmission, and we measured
      GABA dialyzate in CeA after injection of CRF(1) antagonists and ethanol. We also
      compared mRNA expression in CeA for CRF and CRF(1) using real-time polymerase
      chain reaction. We assessed effects of chronic treatment with a CRF(1) antagonist
      on withdrawal-induced increases in alcohol consumption in dependent rats.
      RESULTS: CRF and ethanol augmented CeA GABAergic transmission in naive rats via
      increased GABA release. Three CRF1 receptor (CRF(1)) antagonists decreased basal
      GABAergic responses and abolished ethanol effects. Ethanol-dependent rats
      exhibited heightened sensitivity to CRF and CRF(1) antagonists on CeA GABA
      release. Intra-CeA CRF(1) antagonist administration reversed dependence-related
      elevations in GABA dialysate and blocked ethanol-induced increases in GABA
      dialyzate in both dependent and naive rats. Polymerase chain reaction studies
      indicate increased expression of CRF and CRF(1) in CeA of dependent rats. Chronic
      CRF(1) antagonist treatment blocked withdrawal-induced increases in alcohol
      drinking by dependent rats and tempered moderate increases in alcohol consumption
      by nondependent rats in intermittent testing. CONCLUSIONS: These combined
      findings suggest a key role for specific presynaptic CRF-GABA interactions in CeA
      in the development and maintenance of ethanol dependence.

PMID- 20060107
TI  - A new view of pectin structure revealed by acid hydrolysis and atomic force
      microscopy.
AB  - Individual pectin polymers and complexes, isolated from the pericarp of unripe
      tomato (Lycopersicon esculentum var. Rutgers), were subjected to a mild acid
      hydrolysis and visualised and characterised by atomic force microscopy (AFM). The
      AFM images confirm earlier studies showing that individual pectic polysaccharides
      often possess long branches. The AFM data have been used to construct size and
      molecular weight distributions for the single molecules and complexes, from which
      the calculated number-average and weight-average molecular weights can then be
      compared directly with the published literature data on the rheology of bulk
      samples. Loss of the neutral sugars arabinose, galactose and rhamnose from the
      pectin samples does not significantly alter either the size or the branching
      density of the individual polymers, but is reflected in a breakdown of the
      complexes. Significant loss of galacturonic acid at long hydrolysis times was
      found to be accompanied by changes in the size and branching of the single
      polymers and further breakdown of the complexes. The results suggest that
      rhamnose, arabinose and galactose are not the major components of the individual
      polymers but are, instead, confined to the complexes. The polysaccharides
      represent a previously unrecognised branched homogalacturonan with a minimum mean
      size some three times larger than that previously reported. The complexes consist
      of homogalacturonans (HGs) held together by rhamnogalacturonan I (RG-I) regions.
      Comparison of the rate of depolymerisation of the homogalacturonans and complexes
      with the published data on changes in the intrinsic viscosity of bulk pectin
      samples, subjected to similar acid hydrolysis, suggests that the different rates
      of depolymerisation of RG-I and HG contribute separately to the observed changes
      in intrinsic viscosity during acid hydrolysis. Thus data obtained using a single
      molecule microscopy technique provides new insights into the behaviour in the
      bulk.

PMID- 20060109
TI  - [Primary rectal lymphoma: clinical case and a review of the literature].

PMID- 20060108
TI  - Baculovirus activates murine dendritic cells and induces non-specific NK cell and
      T cell immune responses.
AB  - We previously reported that the baculovirus induced a strong host immune response
      against infections and malignancies. Among the immune cells, the dendritic cells
      were most strongly infected and activated by the baculovirus, although the exact
      mechanism remained unclear. Here, we evaluated the non-specific immune responses
      of bone marrow-derived dendritic cells (BMDCs) after infection by a wild-type
      baculovirus. MHC class I and II molecules and co-stimulation molecules (CD40,
      CD80, and CD86) on BMDCs were up-regulated by baculovirus infection. At the same
      time, the BMDCs produced pre-inflammatory cytokines (IL-6, IL12p70, and TNF
      alpha) and IFN-alpha. NK cells showed IFN-gamma production, CD69 up-regulation,
      and enhanced cytotoxicity when they were co-cultured with baculovirus-infected
      BMDCs. T cells showed IFN-gamma production, CD69 up-regulation, and cell
      proliferation. Ex vivo analysis performed in vitro produced similar results.
      These findings suggested that baculovirus-infected dendritic cells induce non
      specific immune responses and can be used as an immunotherapeutic agent against
      viral infections and malignancies, together with present therapeutic drug
      regimens.

PMID- 20060110
TI  - The cerebellum and dyslexia.

PMID- 20060111
TI  - Extensive video-game experience alters cortical networks for complex visuomotor
      transformations.
AB  - Using event-related functional magnetic resonance imaging (fMRI), we examined the
      effect of video-game experience on the neural control of increasingly complex
      visuomotor tasks. Previously, skilled individuals have demonstrated the use of a
      more efficient movement control brain network, including the prefrontal,
      premotor, primary sensorimotor and parietal cortices. Our results extend and
      generalize this finding by documenting additional prefrontal cortex activity in
      experienced video gamers planning for complex eye-hand coordination tasks that
      are distinct from actual video-game play. These changes in activation between non
      gamers and extensive gamers are putatively related to the increased online
      control and spatial attention required for complex visually guided reaching.
      These data suggest that the basic cortical network for processing complex
      visually guided reaching is altered by extensive video-game play.

PMID- 20060112
TI  - Serum antimullerian hormone (AMH) levels are elevated in adolescent girls with
      polycystic ovaries and the polycystic ovarian syndrome (PCOS).
AB  - Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in adolescents,
      with potentially significant lifelong consequences. This prospective study set
      out to determine if the investigators could derive a threshold value of
      antimullerian hormone (AMH) that would predict its presence according to two
      internationally recognized definitions using a simple measurement, avoiding more
      extensive and potentially more invasive investigations. The study failed to
      demonstrate, in a general adolescent population, that serum AMH is a reliable
      predictor of PCO morphology or for the presence of PCOS.

PMID- 20060114
TI  - p53 expression in human carotid atheroma is significantly related to plaque
      instability and clinical manifestations.
AB  - OBJECTIVE: The expression of p53 has been associated with DNA damage, cell
      senescence, proliferation and apoptosis in human atherosclerotic plaques.
      However, it is largely unknown whether p53 expression is related to the stability
      and clinical manifestations of atherosclerotic plaques in humans. In the present
      study, we examined whether p53 expression is related to clinical symptoms and
      plaque integrity in patients with carotid atherosclerosis (n=62). We also
      investigated p53 expression and its relation to apoptosis and apoptosis-related
      cathepsin L and ferritin in the carotid lesions. METHODS AND RESULTS: We found
      that smooth muscle cells often had nuclear p53 in the shoulder region of carotid
      lesions while CD68-positive macrophages, which had both nuclear and cytoplasmic
      p53, frequently appeared in the surrounding areas of necrotic cores or plaque cap
      regions. Quantitative image analysis of immunohistochemistry showed that p53
      expression was significantly increased in plaques with necrotic core formation or
      cap rupture and lesions from patients with transient ischemic attacks (TIAs). The
      levels of p53 expression was significantly increased in more severe stenosed
      lesions but decreased with prolonged time between symptom onset and carotid
      endarterectomy. Furthermore, p53 expression was significantly correlated with the
      expression of ferritin, lysosomal cathepsin L, and apoptosis. CONCLUSION: The
      increased p53 expression, particularly macrophage p53 levels, is associated with
      the enlargement of necrotic cores, plaque rupture and clinical manifestations of
      carotid plaques. Concomitant increases of lysosomal cathepsin, ferritin, and p53
      levels may promote the apoptosis and atheroma progression in patients with
      carotid atherosclerosis.

PMID- 20060115
TI  - A synonymous variant in scavenger receptor, class B, type I gene is associated
      with lower SR-BI protein expression and function.
AB  - OBJECTIVE: A synonymous variant within scavenger receptor class B type I gene
      (SCARB1), exon 8 rs5888, has been associated with altered lipid levels and
      cardiovascular risk in humans. The objective was to determine if rs5888 decreased
      SR-BI protein expression and function in vitro. METHODS: SR-BI RNA secondary
      structure, turnover, polysomal distribution and protein expression were examined
      in COS cells transfected with wild-type or rs5888-SR-BI plasmids by selective 2'
      hydroxyl acylation and primer extension assays, actinomycin D inhibition,
      polysomal profiling, and western blotting. SR-BI function in murine macrophages
      stably expressing wild-type or rs5888-SR-BI was assessed by measuring the
      specific cell association of (125)I,(3)H-cholesteryl ester (CE) radiolabeled HDL.
      RESULTS: Rs5888 changed RNA secondary structure and led to marked differences in
      the polysomal profiles compared with wild-type transcript (p<0.02). As compared
      to wild-type cells, COS cells expressing rs5888 had significantly lower SR-BI
      protein expression (p<0.04), but no difference in total RNA transcript levels.
      There were no differences in SR-BI RNA turnover in murine macrophages, whereas
      specific cell association of (125)I (p<0.0001) or (3)H-CE (p<0.00001) was
      significantly lower in rs5888 cells. CONCLUSIONS: The rs5888 variant affected SR
      BI RNA secondary structure, protein translation, and was significantly associated
      with reduced SR-BI protein expression and function in vitro.

PMID- 20060116
TI  - Large Brachial Artery Diameter and Metabolic Syndrome in postmenopausal women.
AB  - OBJECTIVE: To investigate on Brachial Artery Diameter enlargement in
      postmenopausal women with Metabolic Syndrome. METHODS: 294 women were admitted
      and classified in two groups according to the presence of Metabolic Syndrome.
      Serum glucose, insulin, lipid profile, carotid arteries and Brachial Artery
      Diameter were measured. RESULTS: Subjects with Metabolic Syndrome had the
      following different parameters in comparison to subjects without Metabolic
      Syndrome: Brachial Artery Diameter, Common Carotid Artery Diameter, IMT, and age.
      In a multivariate regression analysis Brachial Artery Diameter resulted
      correlated to age and presence of Metabolic Syndrome, among the Metabolic
      Syndrome components HDL was the only one to be associated to artery diameter.
      Furthermore, artery diameters increased with the increasing number of Metabolic
      Syndrome components. CONCLUSION: Brachial Artery Diameter enlargement was found
      in postmenopausal women with Metabolic Syndrome. Arterial enlargement seems to be
      a systemic process occurring in response to some factors involved in
      atherosclerosis and not a focal change.

PMID- 20060118
TI  - How accurate is it to report a "protective effect of smoking on metabolic
      syndrome"?

PMID- 20060117
TI  - Ritonavir protects against the development of atherosclerosis in APOE*3-Leiden
      mice.
AB  - OBJECTIVE: The use of the HIV-protease inhibitor ritonavir (RTV) is associated
      with induction of hypertriglyceridemia, which is a cardiovascular risk factor.
      Therefore, we investigated the effect of RTV on atherosclerosis development in
      APOE*3-Leiden transgenic mice, a model for human-like lipoprotein metabolism and
      atherosclerosis. METHODS AND RESULTS: APOE*3-Leiden mice were fed a Western-type
      diet without or with RTV (35 mg/kg/day) for 19 weeks. RTV increased plasma TG
      levels throughout the study (approximately 2-fold; P<0.05). Despite these
      increased TG levels, RTV decreased the atherosclerotic lesion area in the aortic
      root (-57%; P<0.05), concomitant with reduced macrophage area (-72%; P<0.01) and
      decreased lesion severity. This could not be explained by reduced inflammatory
      markers in plasma (i.e. serum amyloid A, E-selectin and fibrinogen), nor by
      decreased lipid accumulation in macrophages or increased cholesterol efflux from
      macrophages, as assessed using peritoneal macrophages in vitro. Rather, whereas
      RTV did not affect plasma total cholesterol levels, RTV decreased (V)LDL
      cholesterol and increased cholesterol in apoE-rich large HDL. CONCLUSION: Despite
      inducing hypertriglyceridemia, RTV decreases atherosclerotic lesion area and
      severity, associated with decreased (V)LDL-cholesterol and increased
      atheroprotective apoE-rich large HDL.

PMID- 20060119
TI  - EAS Summer School 2009 in Hamburg, Germany: "A great opportunity to learn a lot
      about atherosclerosis and to get to know other scientific approaches than one's
      own" (Lujia from Heidelberg, one of this year's participants).

PMID- 20060120
TI  - Anion effects on anti-microbial activity of poly[1-vinyl-3-(2-sulfoethyl
      imidazolium betaine)].
AB  - Recent investigations in the anti-microbial properties of the functional polymers
      are predominantly focused on the structure of the cationic moieties. In the
      present study, we investigated that the nature of the anion present in
      polysulfobetaines affects activity against certain microorganisms and their anti
      microbial properties have been rationalized in terms of the structure-activity
      relationship. Vinyl imidazolium-based polysulfobetaines were prepared by the
      quaternization of poly(N-vinyl imidazole) with sodium salt of 2-bromo
      ethanesulfonic acid. The bromide counter anion of the resulting polymer was
      exchanged with different anions to generate a series of polymers. These were
      characterized by FTIR, DSC, XRD, SEM, elemental analysis (C, H, N and S) and
      viscosity measurements. The anti-microbial activity studies were carried against
      three fungi (Aspergillus niger, Byssochlamys fulva and Mucor circenelliods) and
      two bacteria (Bacillus coagulans BTS-3 and Pseudomonas aeruginosa BTS-2). The
      nature of the anion affects the structure of polysulfobetaine by realignment of
      polymer chains. The anion-dependent anti-microbial properties of
      polysulfobetaines result from the interaction of the microbes at the polymer
      interface.

PMID- 20060121
TI  - Significance of a prominent Q wave in lead negative aVR (-aVR) in acute anterior
      myocardial infarction.
AB  - PURPOSE: The aim of this study was to clarify the significance of a Q wave in
      lead negative aVR (-aVR) in anterior wall acute myocardial infarction (AMI).
      METHODS: Eighty-seven patients with a first anterior wall AMI were classified
      into 2 groups according to the presence (n = 17, group A) or absence (n = 70,
      group B) of a prominent Q wave (duration > or =20 milliseconds) in lead -aVR at
      predischarge. Group A had a higher prevalence of a long left anterior descending
      coronary artery (LAD), a lower left ventricular ejection fraction, and more
      reduced regional wall motion in the apical and inferior regions than group B.
      None of group A patients had an LAD that did not reach the apex. CONCLUSION: A
      prominent Q wave in lead -aVR in anterior wall AMI is related to severe regional
      wall motion abnormality in the apical and inferior regions, with an LAD wrapping
      around the apex.

PMID- 20060122
TI  - Comparison of high-frequency QRS components and ST-segment elevation to detect
      and quantify acute myocardial ischemia.
AB  - OBJECTIVE: This study tests the ability of high-frequency components of the
      depolarization phase (HF-QRS) vs conventional ST-elevation criteria to detect and
      quantify myocardial ischemia. METHODS: Twenty-one patients admitted for elective
      percutaneous coronary intervention were included. Quantification of the ischemia
      was made by myocardial scintigraphy. High-resolution electrocardiogram before and
      during percutaneous coronary intervention was recorded and signal averaged. The
      HF-QRS were determined within the frequency band 150 to 250 Hz. ST-segment
      deviation was measured in the standard frequency range (<100 Hz). RESULTS: HF-QRS
      criteria were met by 76% of the patients, whereas 38% met the ST-elevation
      criteria (P = .008). Both HF-QRS reduction and ST elevation correlated
      significantly with the amount of ischemia (HF-QRS: r = 0.59, P = .005 for extent
      and r = 0.69, P = .001 for severity; ST elevation: r = 0.49, P = .023 for extent
      and r = 0.57, P = .007 for severity). CONCLUSIONS: This study suggests that HF
      QRS analysis could provide valuable information both to detect acute ischemia and
      to quantify myocardial area at risk.

PMID- 20060123
TI  - The diagnostic utility of heart rate-corrected ST-segment depression during
      adenosine nuclear stress testing.
AB  - BACKGROUND: Vasodilator stress testing relies heavily on the imaging portion so
      that clinically useful information from the electrocardiogram may be overlooked.
      Stress-induced ST-segment depression, although uncommon, is highly predictive of
      severe disease. We investigated whether minor ST depressions during adenosine
      nuclear stress testing corrected for the modest heart rate increases (ST/HR slope
      and ST/HR index) might be clinically relevant. METHODS: The study included 74
      consecutive patients with electrocardiograms interpretable for ischemia who
      underwent coronary angiography within the following 6 months. RESULTS: Abnormal
      responses using conventional thresholds for ischemic ST depression, the ST/HR
      slope, and ST/HR index were present in 8%, 20%, and 27%, respectively. The
      sensitivity for conventional ST depression was 11% and, when corrected for heart
      rate, increased to 27% and 36%, (P = .012), without adversely affecting the high
      positive predictive accuracy (83%, 80%, and 80%). Even with a normal perfusion
      scan, heart rate correction was highly predictive of multivessel coronary artery
      disease (4/5 patients). SUMMARY: Heart rate correction of ST depression during
      adenosine nuclear stress improves on conventional ST depression and may
      compliment perfusion imaging in detecting multivessel disease.

PMID- 20060124
TI  - The optimal use of probiotics in acute diarrhea of childhood.

PMID- 20060125
TI  - Dangerous costal exostosis: hemothorax mimicking empyema in a child.

PMID- 20060126
TI  - Nasal glial heterotopia (nasal glioma).

PMID- 20060127
TI  - Neuropsychological profiles in MCI and in depression: Differential cognitive
      dysfunction patterns or similar final common pathway disorder?
AB  - The concept of "mild cognitive impairment" (MCI) refers to alterations in
      cognition in the transition between normal aging and dementia. However, from a
      neuropsychological point of view the conventional diagnostic criteria appear not
      sufficiently valid. In particular, it is still difficult to differentiate between
      subjects with MCI and subjects with depression plus cognitive deficits on the
      basis of their neuropsychological profiles. The aim of this study is to compare
      cognitive deficit patterns of subjects with MCI and with depression. 24 subjects
      with MCI, 50 subjects with depression (DEP) and 20 healthy control subjects were
      included (age: 55-74years). The neuropsychological assessment consisted of
      standardized tests to assess attention, memory, and executive functions. Compared
      to healthy controls both subject groups showed significantly lower performance in
      all cognitive domains. However, we did not find significant differences in
      cognitive performance between MCI and DEP subjects, neither at baseline nor at
      follow-up. In addition, preliminary results of follow-up assessments after 2
      (DEP) and 6months (MCI), respectively, revealed no significant changes in
      cognition in subjects with depression, regardless of whether depressive symptoms
      had improved. Subjects with MCI also showed no changes in cognition at follow-up.
      The comparable neuropsychological patterns identified in the two subject groups
      may be understood as a consequence of similar alterations in cognitive systems,
      supporting the idea of a final common pathway disorder. Thus, the cognitive
      deficits present in a subgroup of subjects with depression may possibly better be
      understood in the context of MCI.

PMID- 20060128
TI  - Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic
      and depressive episodes.
AB  - Bipolar disorder (BD) has been increasingly associated with abnormalities in
      neuroplasticity. Previous studies demonstrated that neurotrophin-3 (NT-3) plays a
      role in the pathophysiology of mood disorders. The influence of medication in
      these studies has been considered a limitation. Thus, studies with drug-free vs.
      medicated patients are necessary to evaluate the role of medication in serum NT-3
      levels. About 10 manic and 10 depressive drug-free, and 10 manic and 10
      depressive medicated patients with BD type I were matched with 20 controls for
      sex and age. Patients were assessed using SCID-I, YMRS and HDRS. Serum NT-3
      levels in drug-free and medicated patients is increased when compared with
      controls (2.51+/-0.59, 2.56+/-0.44 and 1.97+/-0.33, respectively, p<0.001 for
      drug-free/medicated vs. control). Serum NT-3 levels do not differ between
      medicated and drug-free patients. When analyzing patients according to mood
      states, serum NT-3 levels are increased in both manic and depressive episodes, as
      compared with controls (2.47+/-0.43, 2.60+/-0.59 and 1.97+/-0.33, respectively,
      p<0.001 for manic/depressive patients vs. controls). There is no difference in
      serum BDNF between manic and depressive patients. Results suggest that increased
      serum NT-3 levels in BD are likely to be associated with the pathophysiology of
      manic and depressive symptoms.

PMID- 20060129
TI  - Reduced activation and inter-regional functional connectivity of fronto-striatal
      networks in adults with childhood Attention-Deficit Hyperactivity Disorder (ADHD)
      and persisting symptoms during tasks of motor inhibition and cognitive switching.
AB  - Attention-Deficit Hyperactivity Disorder (ADHD) in children has been associated
      with fronto-striatal functional abnormalities during tasks of inhibitory control.
      In adults with ADHD, however, hardly any functional magnetic resonance imaging
      (fMRI) studies have investigated the neurofunctional correlates of the most
      compromised cognitive functions of motor response inhibition and no study has
      investigated cognitive flexibility. In this study we used fMRI to compare brain
      function and task-relevant inter-regional functional connectivity between 11
      medication-naive adults with persistent inattentive/hyperactive behaviours,
      followed up from childhood when they had been diagnosed with ADHD, and 14 age
      matched healthy controls during a Stop and a cognitive Switch tasks. Whole-brain
      regression MR analyses were conducted within patients to correlate symptoms with
      brain activation. Despite comparable task performance, adults with childhood ADHD
      showed reduced activation compared to controls in bilateral inferior prefrontal
      cortex, caudate and thalamus during both tasks, as well as in left parietal lobe
      during the Switch task. Within patients, the severity of the behavioural symptoms
      was negatively correlated with more extensive activation of similar regions in
      fronto-striatal, parietal and cerebellar brain areas. In the Stop task, patients
      showed reduced inter-regional functional connectivity between right inferior
      fronto-frontal, fronto-striatal and fronto-parietal neural networks. The findings
      demonstrate that adults with childhood ADHD and persisting behavioural symptoms
      show strikingly similar patterns of fronto-striatal and parietal dysfunction to
      those observed in childhood ADHD during the same tasks of inhibitory control.
      This suggests that neuro-functional abnormalities in ADHD patients are likely to
      continue between childhood and early adulthood.

PMID- 20060130
TI  - Effects of the HEET garment in the prevention of hypothermia in a porcine model.
AB  - BACKGROUND: Hypothermia is a common battlefield trauma occurrence. This study
      compared the effectiveness of the hypothermia, environmental, exposure, and
      trauma (HEET) garment (Trident Industries, Beaufort, SC) with and without thermal
      inserts with a control group of two wool blankets in the prevention of
      hypothermia in a treated hypovolemic porcine model. MATERIALS AND METHODS: Five
      female swine (Sus scrofa-Yorkshire cross) were assigned to each of three groups:
      HEET with thermal inserts (n=5); HEET without thermal inserts (n=5); or control
      (n=5). After the animals were anesthetized and stabilized for 30 min, the swine
      were hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, simulating a
      battlefield injury. Hetastarch 6% (500 mL) was rapidly administered, simulating
      initial field resuscitation. One hour later, the animals' shed blood was
      reinfused, simulating transfusion at a field medical facility. The investigators
      moved the animal into a cooler set at 10 degrees C +/- 0.5 degrees C. A pulmonary
      artery catheter was used to monitor core body temperature over a 6-h period.
      RESULTS: A repeated measures ANOVA and Tukey's post hoc test were used to analyze
      the data. There was a significant difference between the groups. At the end of
      6h, the mean core temperature for the HEET with inserts group was 32.69 degrees C
      +/- 1.5; the HEET without inserts, 31.02 degrees C +/- 1.8; and control, 34.78
      degrees C +/- 1.2 (P<0.05). While all groups became hypothermic, the wool blanket
      group was most effective in maintaining body temperature closer to normothermia.
      CONCLUSION: The HEET garments with and without heaters are ineffective in
      preventing hypothermia.

PMID- 20060131
TI  - Assessing lesion morphology in MS: why does this matter?

PMID- 20060132
TI  - Methionine sulfoximine, an inhibitor of glutamine synthetase, lowers brain
      glutamine and glutamate in a mouse model of ALS.
AB  - In an effort to alter the levels of neurochemicals involved in excitotoxicity, we
      treated mice with methionine sulfoximine (MSO), an inhibitor of glutamine
      synthetase. Since glutamate toxicity has been proposed as a mechanism for the
      degeneration of motor neurons in a variety of neurodegenerative diseases, we
      tested the effects of MSO on the transgenic mouse that overexpresses the mutant
      human SOD1(G93A) gene, an animal model for the primary inherited form of the
      human neurodegenerative disease amyotrophic lateral sclerosis (ALS). This
      treatment in vivo reduced glutamine synthetase activity measured in vitro by 85%.
      Proton magnetic resonance spectroscopy, with magic angle spinning of intact
      samples of brain tissue, showed that MSO treatment reduced brain levels of
      glutamine by 60% and of glutamate by 30% in both the motor cortex and the
      anterior striatum, while also affecting levels of GABA and glutathione. Kaplan
      Meyer survival analysis revealed that MSO treatment significantly extended the
      lifespan of these mice by 8% (p<0.01). These results show that in the SOD1(G93A)
      model of neurodegenerative diseases, the concentration of brain glutamate
      (determined with (1)H-MRS) can be lowered by inhibiting in vivo the synthesis of
      glutamine with non-toxic doses of MSO.

PMID- 20060133
TI  - An unusual cause of posterior fossa mass: Lhermitte-Duclos disease.
AB  - Lhermitte-Duclos disease (LDD) (dysplastic cerebellar gangliocytoma) is a rare
      disorder of unknown pathogenesis, presenting with signs and symptoms resulting
      from obstruction of cerebrospinal fluid flow and mass effect in the posterior
      fossa. Magnetic resonance imaging is the diagnostic modality of choice allowing
      preoperative diagnosis with characteristic findings. Surgery is the choice of
      treatment. The typical histopathological findings of LDD are characterized by
      widening of the molecular layer, absence of the Purkinje cell layer and
      hypertrophy in the granule cell layer. Herein we report an adolescent girl with
      LDD diagnosed preoperatively by the conventional and advanced MR techniques.

PMID- 20060134
TI  - Adaptation to high light irradiances enhances the photosynthetic Cu2+ resistance
      in Cu2+ tolerant and non-tolerant populations of the brown macroalgae Fucus
      serratus.
AB  - The relationship between light acclimation and Cu(2+) tolerance was studied in
      two populations of Fucus serratus known to be naturally non-tolerant and tolerant
      to Cu(2+). Acclimation to high irradiances increased the photosynthetic tolerance
      to Cu(2+). The xanthophyll cycle was apparently not involved in protecting the
      photosynthetic apparatus against Cu(2+) toxicity, as results showed that Cu(2+)
      did not induce dynamic photoinhibition. The higher photosynthetic Cu(2+)
      resistance of high light algae did not result in increased growth. The excess
      energy acquired by high light-adapted algae appeared to be utilized in Cu(2+)
      defense mechanisms in the Cu(2+) non-tolerant population. The polyphenol content
      of the algae was reciprocal to the Cu(T) content, suggesting that polyphenol may
      be the primary Cu(2+) defense of non-tolerant low light algae, acting through
      secretion and extracellular chelating of Cu(2+), while the compounds do not seem
      to be involved in the primary Cu(2+) tolerance mechanism in Cu(2+) tolerant
      algae.

PMID- 20060135
TI  - An insight into the performance of benthic classification indices tested in
      Eastern Mediterranean coastal waters.
AB  - This work evaluates four indices that have been used for benthic
      macroinvertebrate ecological quality classification in the Mediterranean Sea. Our
      study was based on the data obtained from the participation of Greece and Cyprus
      in the Mediterranean Geographical Intercalibration group. The indices AMBI, M
      AMBI, MEDOCC and BENTIX were applied to the available benthic species data, and
      the succession of the ecological groups along the graded values of each index was
      plotted. The level of agreement among methods was calculated, and the performance
      of each method in estimating ecological quality status was evaluated. AMBI, based
      on the Atlantic model, and its derivative M-AMBI overestimated the statuses,
      while MEDOCC showed the best level of agreement with BENTIX. BENTIX gives equal
      weight to tolerant and opportunistic species groups, which correlates them more
      closely than the other indices and makes BENTIX the most sensitive in detecting
      ecological disturbances in the Eastern Mediterranean basin, where tolerant and
      opportunistic groups seem to play an equally important role in the response of
      benthic communities to stressors.

PMID- 20060136
TI  - Chlorobiphenyls in the blubber of harbour porpoises (Phocoena phocoena) from the
      UK: levels and trends 1991-2005.
AB  - Harbour porpoises sampled within the UK Cetacean Strandings Investigation
      Programme have been analysed for 25 chlorobiphenyl congeners. In all, 440
      porpoises stranded or bycaught during the period 1991-2005 were studied. There
      are regional differences in the trend in summed congener concentrations over time
      but, despite controls on PCBs having been in place for decades, they are
      declining only slowly. Their toxic impacts in UK porpoises - increased
      susceptibility to infectious disease mortality in the most contaminated
      individuals - looks likely to continue for some time yet. Further efforts to
      limit or eliminate PCB discharges to the marine environment are still needed.

PMID- 20060137
TI  - Effects of sheens associated with offshore oil and gas development on the feather
      microstructure of pelagic seabirds.
AB  - Operational discharges of hydrocarbons from maritime activities can have major
      cumulative impacts on marine ecosystems. Small quantities of oil (i.e., 10 ml)
      results in often lethally reduced thermoregulation in seabirds. Thin sheens of
      oil and drilling fluids form around offshore petroleum production structures from
      currently permissible operational discharges of hydrocarbons. Methodology was
      developed to measure feather microstructure impacts (amalgamation index or AI)
      associated with sheen exposure. We collected feather samples from two common
      North Atlantic species of seabirds; Common Murres (Uria aalge) and Dovekies (Alle
      alle). Impacts were compared after feather exposure to crude oil and synthetic
      lubricant sheens of varying thicknesses. Feather weight and microstructure
      changed significantly for both species after exposure to thin sheens of crude oil
      and synthetic drilling fluids. Thus, seabirds may be impacted by thin sheens
      forming around offshore petroleum production facilities from discharged produced
      water containing currently admissible concentrations of hydrocarbons.

PMID- 20060138
TI  - Macroalgae in the coral reefs of Eilat (Gulf of Aqaba, Red Sea) as a possible
      indicator of reef degradation.
AB  - The current state of health of the coral reefs in the northern Gulf of Aqaba (Red
      Sea), notably the Eilat reefs, is under debate regarding both their exact
      condition and the causes of degradation. A dearth of earlier data and unequivocal
      reliable indices are the major problems hinder a clear understanding of the reef
      state. Our research objective was to examine coral-algal dynamics as a potential
      cause and an indication of reef degradation. The community structure of stony
      corals and algae along the northern Gulf of Aqaba reveal non-seasonal turf algae
      dominancy in the shallow Eilat reefs (up to 72%), while the proximate Aqaba reefs
      present negligible turf cover (<6%). We believe that turf dominancy can indicate
      degradation in these reefs, based on the reduction in essential reef components
      followed by proliferation of perennial turf algae. Our findings provide further
      evidence for the severe state of the Eilat coral reefs.

PMID- 20060139
TI  - [Beta-blocking agents in the perioperative period of the non-cardiac surgery].

PMID- 20060140
TI  - [Survival from in-hospital cardiac arrest].

PMID- 20060141
TI  - Current concepts in triglyceride metabolism, pathophysiology, and treatment.
AB  - It is becoming more evident that age, gender, and race play a significant role in
      the metabolic profiles that are seen among individuals in a clinical setting. It
      is important to understand these variances in metabolic profiles; and with these
      variances in mind it is now possible to understand why a single diet might not
      decrease cardiovascular disease risk profiles uniformly for everyone. Much is now
      understood about triglyceride metabolism and its contribution to energy storage.
      In this review we will focus on triglycerides; their production, metabolism and
      influence on daily life, as well as the various methods for the treatment of
      hypertryglyceridemia and prevention of its sequelae.

PMID- 20060142
TI  - Sedentary behavior, physical activity, and concentrations of insulin among US
      adults.
AB  - Time spent watching television has been linked to obesity, metabolic syndrome,
      and diabetes, all conditions characterized to some degree by hyperinsulinemia and
      insulin resistance. However, limited evidence relates screen time (watching
      television or using a computer) directly to concentrations of insulin. We
      examined the cross-sectional associations between time spent watching television
      or using a computer, physical activity, and serum concentrations of insulin using
      data from 2800 participants aged at least 20 years of the 2003-2006 National
      Health and Nutrition Examination Survey. The amount of time spent watching
      television and using a computer as well as physical activity was self-reported.
      The unadjusted geometric mean concentration of insulin increased from 6.2
      microU/mL among participants who did not watch television to 10.0 microU/mL among
      those who watched television for 5 or more hours per day (P = .001). After
      adjustment for age, sex, race or ethnicity, educational status, concentration of
      cotinine, alcohol intake, physical activity, waist circumference, and body mass
      index using multiple linear regression analysis, the log-transformed
      concentrations of insulin were significantly and positively associated with time
      spent watching television (P = < .001). Reported time spent using a computer was
      significantly associated with log-transformed concentrations of insulin before
      but not after accounting for waist circumference and body mass index. Leisure
      time physical activity but not transportation or household physical activity was
      significantly and inversely associated with log-transformed concentrations of
      insulin. Sedentary behavior, particularly the amount of time spent watching
      television, may be an important modifiable determinant of concentrations of
      insulin.

PMID- 20060144
TI  - Association between serum vaspin concentrations and visceral adipose tissue in
      Korean subjects.
AB  - Adipokines modulate multiple signaling pathways of insulin resistance via
      endocrine, paracrine, or autocrine mechanisms. Visceral adipose tissue (VAT)
      derived serpin (vaspin) is a novel adipokine with potential insulin-sensitizing
      effects. We investigated the association between serum vaspin concentrations and
      abdominal adiposity. We recruited subjects (N = 150) aged 20 to 69 years who
      visited our hospital for regular health examinations. Abdominal VAT and
      subcutaneous adipose tissue areas were assessed by computed tomography. We
      measured serum vaspin concentrations by enzyme-linked immunosorbent assay.
      Statistical analysis was performed after stratification, using a homeostasis
      model for insulin resistance (HOMA-IR). Serum vaspin concentrations correlated
      positively with age (r = 0.196) when data from all subjects were analyzed. In the
      higher-HOMA-IR group, serum vaspin levels correlated more prominently with age (r
      = .344) and VAT area (r = .327) although these associations were not found in the
      lower-HOMA-IR group. In multivariate linear regression analysis, the VAT area was
      independently correlated with serum vaspin concentrations in the higher-HOMA-IR
      group. The association between serum vaspin concentrations and VAT differs
      according to insulin resistance. Insulin resistance might influence the
      correlation between serum vaspin concentration and VAT in human subjects.

PMID- 20060143
TI  - Dietary fat intake promotes the development of hepatic steatosis independently
      from excess caloric consumption in a murine model.
AB  - Nonalcoholic fatty liver disease results from overconsumption and is a
      significant and increasing cause of liver failure. The type of diet that is
      conducive to the development of this disease has not been established, and
      evidence-based treatment options are currently lacking. We hypothesized that the
      onset of hepatic steatosis is linked to the consumption of a diet with a high fat
      content, rather than related to excess caloric intake. In addition, we also
      hypothesized that fully manifested hepatic steatosis could be reversed by
      reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were
      fed either a purified rodent diet containing 10% fat or a diet with 60% of
      calories derived from fat. A pair-feeding design was used to distinguish the
      effects of dietary fat content and caloric intake on dietary-induced hepatic
      lipid accumulation and associated injury. Livers were analyzed by quantitative
      reverse transcriptase polymerase chain reaction for lipid metabolism-related gene
      expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain,
      insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet
      with equal caloric intake. Furthermore, mice with established metabolic syndrome
      at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity
      when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric
      intake. Quantitative reverse transcriptase polymerase chain reaction revealed
      that transcripts related to both de novo lipogenesis and increased uptake of free
      fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet
      compared with 10%-fat-fed animals. Dietary fat content, independent from caloric
      intake, is a crucial factor in the development of hepatic steatosis, obesity, and
      insulin resistance in the C57BL/6J diet-induced obesity model caused by increased
      uptake of free fatty acids and de novo lipogenesis. In addition, once
      established, all these features of the metabolic syndrome can be successfully
      reversed after switching obese mice to a diet low in fat. Low-fat diets deserve
      attention in the investigation of a potential treatment of patients with
      nonalcoholic fatty liver disease.

PMID- 20060145
TI  - Short-term effect of concentrations of fine particulate matter on hospital
      admissions due to cardiovascular and respiratory causes among the over-75 age
      group in Madrid, Spain.
AB  - OBJECTIVES: This study sought to analyse the effect of daily mean concentrations
      of fine particulate matter (diameter <2.5 microm; PM(2.5)) on hospital admissions
      due to circulatory and respiratory causes among an elderly population (>75 years)
      in Madrid between 2003 and 2005. STUDY DESIGN: Ecological longitudinal time
      series study. METHODS: The dependent variable used was the daily number of
      emergency hospital admissions registered at the Gregorio Maranon University
      Teaching Hospital. The following causes were analysed: all causes [International
      Classification of Diseases 9th Version (ICD-9:1-799)], respiratory causes (ICD-9:
      460-519) and circulatory causes (ICD-9: 390-459). Analysis focused on subjects
      over 75 years of age. Daily records of mean concentrations of PM(2.5), PM(10),
      NO(2), NO(x), SO(2) and O(3) in Madrid were used as independent variables. The
      control variables were seasonalities, trend, influenza epidemics, noise and
      pollen concentrations. Poisson regression models were constructed to calculate
      the relative risk (RR) and attributable risk (AR). Analyses were performed for
      the entire year and for the winter and summer. RESULTS: PM(2.5) was the single
      primary pollutant that proved statistically significant in all models. The
      functional relationship with hospital admissions was linear and had no threshold.
      Taking the year as a whole, the RRs among people over 75 years of age for an
      increase of 10 microg/m(3) in PM(2.5) concentrations were: 1.038 [95% confidence
      interval (CI) 1.022-1.053] for all causes at lag 0; 1.062 (95% CI 1.036-1.089)
      for circulatory causes at lag 0; and 1.049 (95% CI 1.019-1.078) for respiratory
      causes at lag 3. The ARs were 3.6%, 5.9% and 4.6%, respectively. These risks
      increased in winter and no statistically significant associations were observed
      in summer. PM(2.5) was the only primary pollutant that showed a statistically
      significant association with hospital admissions among people over 75 years of
      age in Madrid across the study period. CONCLUSION: Measures should be implemented
      to reduce PM(2.5) concentrations in Madrid.

PMID- 20060146
TI  - Invasive carcinoma derived from the nonintestinal type intraductal papillary
      mucinous neoplasm of the pancreas has a poorer prognosis than that derived from
      the intestinal type.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is
      divided into 4 subtypes: an intestinal type, a gastric type, a pancreatobiliary
      type, and an oncocytic type. The purposes of this study were to clarify the
      outcomes and the characteristics of invasive carcinoma derived from IPMN
      (invasive IPMC) by focusing on these subtypes with a comparison to conventional
      invasive ductal carcinoma (IDC) of the pancreas. METHODS: A total of 30 patients
      with invasive IPMC were reviewed, and the tumors were divided into 2 pathologic
      subtypes, intestinal and nonintestinal type. The prognosis and characteristics of
      the 2 subtypes were evaluated. Furthermore, the prognosis of 119 patients with
      conventional IDC was compared with that of patients with invasive carcinoma
      derived from the intestinal or nonintestinal type IPMN. RESULTS: The 5-year
      survival rate of patients with the nonintestinal type (0.0%) was as poor as that
      of patients with conventional IDC (19.9%; P = .67). The patients with the
      intestinal type (66.7%) had a more favorable prognosis than patients with
      conventional IDC (P < .001). The nonintestinal type was characterized by positive
      lymphatic invasion and tubular invasive pattern. CONCLUSION: Invasive carcinoma
      derived from the nonintestinal type IPMN characterized by lymphatic invasion and
      tubular invasive pattern is associated with a poor prognosis.

PMID- 20060147
TI  - Hydroxylated polychlorinated biphenyls (OH-PCBs) induce vitellogenin through
      estrogenic activity in primary-cultured hepatocytes of the Xenopus laevis.
AB  - Vitellogenin (VTG)-inducing activities of 21 kinds of hydroxylated
      polychlorinated biphenyls (OH-PCBs) were investigated by an assay system using
      the primary-cultured hepatocyte of the adult male Xenopus laevis. An enzyme
      linked immunoabsorbent assay (ELISA) was able to detect VTG at a minimum
      detection limit of 0.2ngmL(-1). The levels of VTG production in hepatocytes of
      male X. laevis exposed to six kinds of OH-PCB isomers (2'-OH-CB30, 3'-OH-CB30, 4'
      OH-CB30, 4'-OH-CB50, 4'-OH-CB61 4'-OH-CB65) were significantly higher as compared
      to the control group (p<0.05). The relative ranking of the OH-PCBs was E2 (100%),
      4'-OH-CB30 (2.0%)>2'-OH-CB30 (0.15%)>4'-OH-CB61 (0.046%)>3'-OH-CB30 (0.013%)>4'
      OH-CB50 (0.002%)>4'-OH-CB65 (0.0001%). Although there were some differences
      between the estrogenicity values by the VTG-inducing activities and yeast two
      hybrid assay for human estrogen receptor alpha (ERalpha). The results from VTG
      assays suggested that an important factor for determining estrogenicity is the
      positions of the hydroxyl group and chlorine with the highest activity resulting
      from a para-hydroxyl group. The OH-PCB structures of high rank order in the VTG
      assay had no chlorine substituted phenolic ring. Moreover, the meta-chlorine
      substituted phenolic ring is an important factor in determining estrogenicity.
      The OH-PCBs with meta-chlorine substituted phenolic ring did not show
      estrogenicity during VTG-assay.

PMID- 20060148
TI  - Chemical contaminants in fish species from rivers in the North of Luxembourg:
      Potential impact on the Eurasian otter (Lutra lutra).
AB  - Contamination levels of PCBs, and of the heavy metals cadmium (Cd), lead (Pb) and
      mercury (Hg) were analyzed in four fish species from seven rivers in the North of
      Luxembourg. During August and September 2007, 85 samples of fish were collected
      belonging to four species: the stone loach (Barbatula barbatula, n=12 pools), the
      chub (Squalius cephalus, n=36), the barbel (Barbus barbus, n=23) and eel
      (Anguilla anguilla, n=14). The concentration of seven indicator PCBs ( summation
      operator(7)PCBs) reached a mean of 39ngg(-1) and varied between 4.0 and 346.2ngg(
      1) (wet wt) depending on the site and species. Fish collected at Wallendorf on
      the Our River and sites on the Wiltz and the Clerve rivers showed the highest
      concentrations for PCBs. In comparison with 1994, PCB levels in fish decreased
      strongly during the last decade in these rivers. Lead was detected at low levels
      (0-181.4ngg(-1) wet wt). Mercury concentrations ranged between 10.3 and 534.5ngg(
      1) (wet wt) exceeding maximum tolerable levels for human consumption of 500ngg(
      1) in two fish out of 85. Chubs and eels from the Sure River were the most
      contaminated by mercury. Cadmium levels varied between 4.0 and 103.9ngg(-1) (wet
      wt). In addition to mercury in fish, cadmium was the most problematic pollutant
      on the Our, the Wiltz, the Clerve and the Troine Rivers, because values found in
      20% of fish exceeded the threshold of about 10-50ngg(-1) (wet wt) recommended for
      human health. The total PCB level predicted to accumulate in livers from otter
      potentially feeding on these fish based on a previously published mathematical
      model is 37.7microgg(-1) (lipid wt), which is between a proposed "safe level" and
      a "critical level" for otters. Rivers in the North of Luxembourg are thus to some
      extent polluted, and the establishment of otter populations could be affected by
      current levels of contamination.

PMID- 20060149
TI  - Cadmium accumulation and distribution in populations of Phytolacca americana L.
      and the role of transpiration.
AB  - The concentrations of heavy metals in Phytolacca americana L. and corresponding
      soil samples from three contaminated sites and an uncontaminated site were
      studied. Hydroponic experiments were also conducted to investigate the Cd uptake
      ability and mechanism of P. americana. The field results showed that the average
      Cd concentration was 42 mg kg(-1) in P. americana leaves, with the highest
      concentration of 402 mg kg(-1) found at Datianwan. A significant relationship was
      observed between the concentrations of Cd in leaves and those of corresponding
      soils on a logarithmic scale. Under laboratory hydroponic conditions, the maximum
      Cd concentration in aerial tissues of P. americana was 637 mg kg(-1), under
      treatment with 100 microM Cd. The population from the uncontaminated site
      (Zijinshan) also had a remarkable ability to accumulate Cd in shoots to
      concentrations well in excess of 100 microM in the hydroponic experiment, similar
      to the population from contaminated site, suggesting that Cd accumulation is a
      constitutive trait of P. americana. In the presence of 100 microM Cd, the
      addition of polyethylene glycol decreased leaf transpiration, the shoot Cd
      concentration, and the shoot/root Cd concentration ratio. There was a
      significantly positive relationship between the shoot Cd concentration and the
      leaf transpiration of P. americana. A similar significant positive correlation
      was also obtained between the shoot/root Cd concentration and leaf transpiration.
      Moreover, pretreatment with 5 microM abscisic acid or 5 microM HgCl(2)
      significantly decreased the Cd concentration in P. americana shoots. These
      results suggest that transpiration has an important role in Cd accumulation in
      shoots of P. americana.

PMID- 20060150
TI  - Experimental study on the effects of H(2)O on PCDD/Fs formation by de novo
      synthesis in carbon/CuCl(2) model system.
AB  - The effects of H(2)O vapor on de novo synthesis of polychlorinated dibenzo-p
      dioxins and dibenzofurans (PCDD/Fs) and biphenyls (PCB) were investigated at two
      levels (none and 10 vol.%) in various model systems containing five different
      carbons, CuCl(2), and quartz, exposed to a flow of 10% O(2)/N(2) at 300 degrees
      Celsius. The influence of H(2)O was studied on (1) speciation and behavior of
      copper compounds, (2) catalytic oxidation of carbons of distinct reactivity, and
      (3) formation of organic chlorine compounds, with the aim to investigate any
      effects on de novo synthesis. It is found that H(2)O converts CuCl(2) to CuCl(2)
      x CuO, and finally to CuO in a flow of 10% O(2)/N(2) at 300 degrees Celsius and
      that it decreases of organic chlorine (C-Cl) formation. When CuCl(2) is supported
      on carbon, the addition of H(2)O promotes the catalytic oxidation of this carbon.
      When CuCl(2) is supported on quartz, however, H(2)O inhibits carbon oxidation. A
      decrease in chlorination level of PCDD/Fs and PCBs with water addition is
      observed for all (six) model ashes; yet this addition affects the yields of
      PCDD/Fs and PCBs differently. Under the experimental conditions tested H(2)O does
      not react with Cu(2)Cl(2), which is the catalyst of carbon oxidation. On the
      basis of the experimental results, the following mechanism is proposed:
      conversion of CuCl(2) into CuO which is less reactive in de novo synthesis and
      promotion of catalytic oxidation of carbon by Cu(2)Cl(2).

PMID- 20060151
TI  - Polybrominated diphenyl ethers (PBDEs) in selected fish species from the southern
      Baltic Sea.
AB  - This paper reports concentrations of seven polybrominated diphenyl ether (PBDE)
      congeners in selected fish species that were collected from the southern Baltic
      in the 2004-2006 period. Differences in concentrations of PBDEs among the fish
      species were observed. The mean summation Sigma(7)PBDE concentrations measured in
      herring (Clupeaharengus), sprat (Sprattus sprattus), and salmon (Salmo salar)
      samples were 1.2 ng g(-1) wet weight, 1.6 ng g(-1) wet weight, and 2.5 ng g(-1)
      wet weight, respectively. PBDE-47 was the prevalent congener in all the samples
      tested. PBDE concentrations in the herring samples tested in the current study
      were similar to those determined in herring sampled in the northern Baltic, but
      slightly lower in comparison with concentrations in fish from the Belgian North
      Sea. PBDE levels occurring in salmon sampled in the southern Baltic were lower
      than those measured in the northern and northeastern Baltic, but similar to
      levels determined in salmon from the central part of the Baltic Sea. The risk
      posed by consuming the fish tested in the current study was evaluated according
      to the Provisional Tolerable Weekly Intake (PTWI) value for PBDEs recommended by
      the European Food Safety Authority (EFSA).

PMID- 20060152
TI  - Clear cell adenocarcinoma of the bladder and urethra: cases diffusely mimicking
      nephrogenic adenoma.
AB  - Although clear cell adenocarcinoma have been described focally mimicking
      nephrogenic adenoma, we have identified a subset of clear cell adenocarcinoma
      that diffusely resembles nephrogenic adenoma (nephrogenic adenoma-like clear cell
      adenocarcinoma). Twelve classic clear cell adenocarcinomas of the bladder and
      urethra and 7 nephrogenic adenoma-like clear cell adenocarcinomas were compared
      to 10 nephrogenic adenomas. Classic clear cell adenocarcinomas and nephrogenic
      adenoma-like clear cell adenocarcinomas comprised 4 men and 15 women. The
      following features were seen in classic clear cell adenocarcinomas: nephrogenic
      adenoma-like clear cell adenocarcinomas: predominantly solid pattern (7/12:0/7),
      marked nuclear pleomorphism (7/12:1/7), prominent nucleoli (5/12:1/7), clear
      cytoplasm in 50% or greater of tumor (7/12:0/7), and necrosis (8/12:3/7),
      although the necrosis in nephrogenic adenoma-like clear cell adenocarcinomas was
      often focal and intraluminal. Both patterns of clear cell adenocarcinomas showed
      prominent hobnail features, although more pronounced in nephrogenic adenoma-like
      clear cell adenocarcinomas. Muscularis propria invasion was seen in 5 of 9
      classic clear cell adenocarcinomas and 6 of 6 nephrogenic adenoma-like clear cell
      adenocarcinomas, where evaluable. Classic clear cell adenocarcinoma was
      associated with urothelial carcinoma (n = 2) and endometriosis (n = 1). The Ki-67
      rate in clear cell adenocarcinomas ranged from 10% to 80% compared with 0% to 5%
      in nephrogenic adenoma. The following antibodies were not helpful in
      distinguishing nephrogenic adenoma-like clear cell adenocarcinoma from
      nephrogenic adenoma: CD10, estrogen receptor, p63, high-molecular-weight
      cytokeratin, and alpha-methylacyl coenzyme-A racemase. PAX2 expression was more
      frequent in nephrogenic adenoma (89%) compared to both patterns of clear cell
      adenocarcinoma (29%-32%). The key features discriminating between nephrogenic
      adenoma-like clear cell adenocarcinoma and nephrogenic adenoma include occasional
      clear cells, more prominent pleomorphism especially hyperchromatic enlarged
      nuclei, and extensive muscular invasion. Presence of mitoses and a high rate of
      Ki-67 expression in lesions resembling nephrogenic adenoma require clinical
      correlation, close follow-up, and repeat biopsy with more extensive sampling.

PMID- 20060153
TI  - Virtual 3D microscopy in pathology education.

PMID- 20060154
TI  - Grading system for lymph vessel tumor emboli: significant outcome predictor for
      invasive ductal carcinoma of the breast.
AB  - The purpose of this study was to confirm that the grading system for lymph vessel
      tumor emboli is a significant histologic outcome predictor for patients with
      invasive ductal carcinoma. The subjects of this study were 1042 invasive ductal
      carcinoma patients who did not receive neoadjuvant therapy. We classified all
      invasive ductal carcinomas according to the grading system for lymph vessel tumor
      emboli we devised, and performed multivariate analyses with well-known prognostic
      factors. Of 1042 carcinomas, 666, 250, 97, and 29 were classified according to
      the grading system for lymph vessel tumor emboli as grade 0 (no lymph vessel
      invasion), grade 1, grade 2, and grade 3, respectively. The univariate analyses
      showed that the difference in outcome between the group with grade 0 and the
      group with grade 1 was not significant, but that survival time was significantly
      shorter in the group of patients with grade 2 carcinomas than in the group with
      grade 1 carcinomas and significantly shorter in the group of patients with grade
      3 carcinomas than in the group with grade 2 carcinomas. Multivariate analyses
      demonstrated that having a grade 2 or grade 3 carcinoma significantly increased
      the hazard rates for tumor recurrence and tumor-related death in the patients as
      a whole as well as in both the group of patients with nodal metastasis and the
      group without nodal metastasis. The grading system for lymph vessel tumor emboli
      is an excellent histologic grading system for predicting the outcome of patients
      with invasive ductal carcinoma of the breast.

PMID- 20060155
TI  - On being a pathologist--full circle.

PMID- 20060156
TI  - Overexpression of matrix metalloproteinase 11 in human gastric carcinoma and its
      clinicopathologic significance.
AB  - Matrix metalloproteinase 11 (stromelysin-3) has recently been reported to play a
      key role in human tumor progression and poor clinical outcome. The aim of this
      study was to investigate the significance of matrix metalloproteinase 11
      expression in gastric cancer. Using real-time quantitative reverse-transcription
      polymerase chain reaction analysis and immunohistochemistry, we studied matrix
      metalloproteinase 11 expression levels in non-malignant gastric tissues and in
      gastric cancer tissues. The association between matrix metalloproteinase 11
      expression levels and tumor stage and grade, as well as metastatic potential, was
      analyzed. Our results show that matrix metalloproteinase 11 expression was
      significantly higher in gastric cancer specimens compared with nonmalignant
      tissues at both transcriptional and protein levels, indicating its positive role
      in the development of gastric cancer. In addition, increased matrix
      metalloproteinase 11 expression levels were associated with advanced-stage and
      high-grade tumors, suggesting its involvement in the progression of gastric
      cancer. More importantly, increased matrix metalloproteinase 11 expression in
      gastric cancer specimens was correlated with increased expression of IGF-1, a
      molecule known to stimulate the proliferation, enhanced survival, and migration
      of cancer cells. Our results demonstrate that matrix metalloproteinase 11 is a
      novel factor in the development and progression of gastric cancer and suggest
      that matrix metalloproteinase 11 is a marker for advanced gastric cancer.

PMID- 20060157
TI  - IMP3/L523S, a novel immunocytochemical marker that distinguishes benign and
      malignant cells: the expression profiles of IMP3/L523S in effusion cytology.
AB  - Differentiating reactive mesothelial cells from metastatic carcinoma and
      malignant mesothelioma is critical in effusion cytology. Numerous
      immunohistochemical/cytochemical reports use various antibodies in effusion
      samples, and most antibodies differentiate metastatic adenocarcinoma from
      malignant mesothelioma, but no antibodies help distinguish malignant mesothelioma
      from reactive mesothelial cells. A mouse monoclonal antibody (IMP3/L523S) against
      KOC is a 580-amino acid oncofetal RNA-binding protein containing 4 K homology
      domains. IMP3/L523S has been identified in several human malignant tumors. The
      immunocytochemical staining profile of IMP3 was determined in 95% alcohol-fixed
      cytologic effusion specimens. A total of 229 cases of pleural and peritoneal
      effusion cytospecimens were evaluated for the study, including 39 benign
      effusions with reactive mesothelial cells and 190 metastatic malignant effusions.
      IMP3 immunoreactivity was observed in 2 (5.1%) of 39 cases of reactive
      mesothelial cells, 138 (72.6%) of 190 cases of malignant effusion, 4 (36.4%) of
      11 cases of malignant mesothelioma, 106 (75.7%) of 140 cases of metastatic
      adenocarcinoma, and 8 (100%) of 8 cases of squamous cell carcinoma. The overall
      specificity for the diagnosis of malignancy was 94.9%, whereas the sensitivity
      was 72.6%. In the peritoneal effusions, the sensitivity for the diagnosis of
      metastatic adenocarcinoma to distinguish reactive mesothelial cells was 92.3%. In
      conclusion, IMP3 staining is present in many carcinomas and is not a useful
      marker for distinguishing between carcinomas arising in different organs.
      However, the IMP3 antibody is a highly specific marker for malignant lesions, and
      thus, IMP3 staining is useful for distinguishing neoplastic cells from reactive
      mesothelial cells in effusion samples.

PMID- 20060158
TI  - The number of metastatic sites for stage IIIA endometrial carcinoma, endometrioid
      cell type, is a strong negative prognostic factor.
AB  - The aim of this study was to look at the impact of the number of sites with
      tumour involvement on outcome for patients with stage IIIA endometrioid-type
      endometrial carcinoma. PATIENTS AND METHODS: 141 patients stage IIIA were
      included. A central histopathological review was performed. Patients staged
      solely on the presence of a positive peritoneal washing were excluded. Follow-up
      ranged from 2 to 217 months with a median of 43 months. Endpoints of the study
      were locoregional recurrence rates, distant metastasis-free survival (DMFS),
      disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: In
      multivariate analyses the number of involved sites showed to be the only
      independent significant variable for DMFS, DFS, and DSS with a Hazard Ratio of
      2.1, 2.2, and 2.2, respectively. The DSS was significantly related to the number
      of involved sites, with a 5-year DSS of 70.4% for one site, 42.8% for two sites,
      and 43.9% for three sites, respectively (p=0.001). CONCLUSION: The number of
      involved sites outside the corpus uterine for stage IIIA seems to be a strong
      negative prognostic factor for stage IIIA endometrial carcinoma.

PMID- 20060159
TI  - Introduction to and outcomes of the conference on adhesion in dentistry.

PMID- 20060160
TI  - Direct comparison of the bond strength results of the different test methods: a
      critical literature review.
AB  - OBJECTIVE: The goal of this paper is to undertake a literature search collecting
      all dentin bond strength data obtained for six adhesives with four tests (shear,
      microshear, tensile and microtensile) and to critically analyze the results with
      respect to average bond strength, coefficient of variation, mode of failure and
      product ranking. METHOD: A PubMed search was carried out for the years between
      1998 and 2009 identifying publications on bond strength measurements of resin
      composite to dentin using four tests: shear, tensile, microshear and
      microtensile. The six adhesive resins were selected covering three step systems
      (OptiBond FL, Scotch Bond Multi-Purpose Plus), two-step (Prime & Bond NT, Single
      Bond, Clearfil SE Bond) and one step (Adper Prompt L Pop). RESULTS: Pooling
      results from 147 references showed an ongoing high scatter in the bond strength
      data regardless which adhesive and which bond test was used. Coefficients of
      variation remained high (20-50%) even with the microbond test. The reported modes
      of failure for all tests still included high number of cohesive failures. The
      ranking seemed to be dependant on the test used. SIGNIFICANCE: The scatter in
      dentin bond strength data remains regardless which test is used confirming Finite
      Element Analysis predicting non-uniform stress distributions due to a number of
      geometrical, loading, material properties and specimens preparation variables.
      This reopens the question whether, an interfacial fracture mechanics approach to
      analyze the dentin-adhesive bond is not more appropriate for obtaining better
      agreement among dentin bond related papers.

PMID- 20060161
TI  - Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin
      in women not exposed to oxytocin during labour: a double-blind, randomised, non
      inferiority trial.
AB  - BACKGROUND: Oxytocin, the standard of care for treatment of post-partum
      haemorrhage, is not available in all settings because of refrigeration
      requirements and the need for intravenous administration. Misoprostol, an
      effective uterotonic agent with several advantages for resource-poor settings,
      has been investigated as an alternative. This trial established whether
      sublingual misoprostol was similarly efficacious to intravenous oxytocin for
      treatment of post-partum haemorrhage in women not exposed to oxytocin during
      labour. METHODS: In this double-blind, non-inferiority trial, 9348 women not
      exposed to prophylactic oxytocin had blood loss measured after vaginal delivery
      at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three
      tertiary-level facilities). 978 (10%) women were diagnosed with primary post
      partum haemorrhage and were randomly assigned to receive 800 microg misoprostol
      (n=488) or 40 IU intravenous oxytocin (n=490). Providers and women were masked to
      treatment assignment. Primary endpoints were cessation of active bleeding within
      20 min and additional blood loss of 300 mL or more after treatment. Clinical
      equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI
      fell below the predefined non-inferiority margin of 6%. All outcomes were
      assessed from the time of initial treatment. This study is registered with
      ClinicalTrials.gov, number NCT00116350. FINDINGS: All randomly assigned
      participants were analysed. Active bleeding was controlled within 20 min with
      study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given
      oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95%
      CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred
      for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR
      1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25
      3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more
      common with misoprostol than with oxytocin. No women had hysterectomies or died.
      INTERPRETATION: In settings in which use of oxytocin is not feasible, misoprostol
      might be a suitable first-line treatment alternative for post-partum haemorrhage.

PMID- 20060162
TI  - Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin
      in women receiving prophylactic oxytocin: a double-blind, randomised, non
      inferiority trial.
AB  - BACKGROUND: Oxytocin, the gold-standard treatment for post-partum haemorrhage,
      needs refrigeration, intravenous infusion, and skilled providers for optimum use.
      Misoprostol, a potential alternative, is increasingly used ad hoc for treatment
      of post-partum haemorrhage; however, evidence is insufficient to lend support to
      recommendations for its use. This trial established whether sublingual
      misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum
      haemorrhage in women receiving prophylactic oxytocin. METHODS: In this double
      blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had
      blood loss measured after vaginal delivery at five hospitals in Burkina Faso,
      Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level
      facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were
      randomly assigned to receive 800 mug misoprostol (n=407) or 40 IU intravenous
      oxytocin (n=402). Providers and women were masked to treatment assignment.
      Primary endpoints were cessation of active bleeding within 20 min and additional
      blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol
      would be accepted if the upper bound of the 97.5% CI fell below the predefined
      non-inferiority margin of 6%. All outcomes were assessed from the time of initial
      treatment. This study is registered with ClinicalTrials.gov, number NCT00116350.
      FINDINGS: All randomly assigned participants were analysed. Active bleeding was
      controlled within 20 min after initial treatment for 363 (89%) women given
      misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95
      1.04; crude difference 0.4%, 95% CI -3.9 to 4.6). Additional blood loss of 300 mL
      or greater after treatment occurred for 139 (34%) women receiving misoprostol and
      123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs
      59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09
      1.99) were significantly more common with misoprostol than with oxytocin. Six
      women had hysterectomies and two women died. INTERPRETATION: Misoprostol is
      clinically equivalent to oxytocin when used to stop excessive post-partum
      bleeding suspected to be due to uterine atony in women who have received oxytocin
      prophylactically during the third stage of labour.

PMID- 20060163
TI  - Trophoblast Research. Preface.

PMID- 20060164
TI  - Mesenchymal stem cells in human placental chorionic villi reside in a vascular
      Niche.
AB  - The chorionic villi of human term placentae are a rich source of mesenchymal stem
      cells (PMSCs). The stem cell "niche" within the chorionic villi regulates how
      PMSCs participate in placental tissue generation, maintenance and repair, but the
      anatomic location of the niche has not been defined. A number of cell surface
      markers for phenotypic characterisation of mesenchymal stem cells (MSCs) were
      employed to identify the stem cell niche within the chorionic villi of first
      trimester and term human placenta. This included antibodies to pericyte cell
      surface markers STRO-1 and 3G5, which have been used to identify mesenchymal stem
      cells in other tissues, but have not been studied in placental tissues. PMSCs
      were isolated from term human placentae and shown to have stem cell properties by
      their ability to grow on untreated plastic culture ware, capacity for forming
      clones (i.e. clonogenicity) and their capability to differentiate into
      adipocytes, chondrocytes and osteocytes. Western analysis confirmed that STRO-1
      and 3G5 are present in placental protein extracts and in PMSCs.
      Immunocytochemistry revealed PMSCs were positive for MSC cell surface markers
      (STRO-1, 3G5, CD105, CD106, CD146, CD49a, alpha-SMA) and negative for
      haematopoietic stem cell markers (CD117, CD34) and endothelial markers (CD34,
      vWF). Immunohistochemistry with antibodies to MSC cell surface markers on first
      trimester and term tissues revealed a vascular niche for PMSCs. Dual-label
      immunofluorescence analysis was used to compare STRO-1 antibody staining with
      that of endothelial cell marker vWF and found no significant overlap in staining.
      This indicated that some PMSCs have a pericyte-like phenotype. We propose that
      the vascular niche harbours a pool of PMSCs that can give rise to committed
      progenitors for tissue maintenance and repair, and that PMSCs contribute to
      vessel maturation and stabilization.

PMID- 20060166
TI  - A case of ATRA-induced isolated myocarditis in the absence of circulating
      malignant cells: demonstration of the t(15;17) translocation in the inflammatory
      infiltrate by in situ hybridisation.

PMID- 20060165
TI  - Preventing Ca2+-mediated nitrosative stress in neurodegenerative diseases:
      possible pharmacological strategies.
AB  - Overactivation of the NMDA-subtype of glutamate receptor is known to trigger
      excessive calcium influx, contributing to neurodegenerative conditions. Such
      dysregulation of calcium signaling results in generation of excessive free
      radicals, including reactive oxygen and nitrogen species (ROS/RNS), including
      nitric oxide (NO). In turn, we and our colleagues have shown that these free
      radicals trigger pathological production of misfolded proteins, mitochondrial
      dysfunction, and apoptotic pathways in neuronal cells. Here, we discuss emerging
      evidence that excessive calcium-induced NO production can contribute to the
      accumulation of misfolded proteins, specifically by S-nitrosylation of the
      ubiquitin E3 ligase, parkin, and the chaperone enzyme for nascent protein
      folding, protein-disulfide isomerase. Additionally, excessive calcium-induced NO
      generation leads to the formation of S-nitrosylated dynamin-related protein 1,
      which causes abnormal mitochondrial fragmentation and resultant synaptic damage.
      In this review, we also discuss how two novel classes of pharmacological agents
      hold promise to interrupt these pathological processes. Firstly, the NMDA
      receptor antagonists, Memantine and NitroMemantine, block excessive extrasynaptic
      glutamate excitation while maintaining synaptic transmission, thereby limiting
      excessive calcium influx and production of ROS/RNS. Secondly, therapeutic pro
      electrophiles are activated in the face of oxidative insult, thus protecting
      cells from calcium-induced oxidative stress via the Keap1/Nrf2 transcriptional
      pathway.

PMID- 20060167
TI  - Limbal stem cell deficiency after topical mitomycin C therapy for primary
      acquired melanosis with atypia.
AB  - PURPOSE: To describe the incidence, characteristics, risk factors, and clinical
      outcome of limbal stem cell deficiency (LSCD) resulting from topical treatment
      with mitomycin C (MMC) for primary acquired melanosis (PAM) with atypia. DESIGN:
      Retrospective, observational case series. PARTICIPANTS: Patients with LSCD who
      had been managed with topical MMC for PAM with atypia at the Ocular Oncology
      Service at the Department of Ophthalmology, Hadassah-Hebrew University Medical
      Center, Jerusalem, Israel, between 2000 and 2007. METHODS: Retrospective chart
      review of all patients with PAM with atypia was performed. Impression cytologic
      analysis of the corneal and conjunctival epithelium was performed in patients
      suspected of having LSCD. MAIN OUTCOME MEASURES: Evaluation of risk factors for
      LSCD, including demographic characteristics, MMC dosage, and length of treatment;
      and clinical and visual outcome of patients diagnosed with LSCD. RESULTS: Limbal
      stem cell deficiency was identified in 5 (23.8%) of 21 patients. The mean age+/
      standard deviation of the 5 patients was 61.8+/-12.7 years compared with 43.7+/
      16.1 years in patients in whom this complication did not develop (P = 0.025).
      Longer treatment periods of MMC were noted in eyes in which LSCD developed
      (78.4+/-24.8 days) compared with eyes without LSCD (37.7+/-3.1 days; P = 0.07).
      In 3 patients, spontaneous partial resolution of the LSCD was noted. CONCLUSIONS:
      High-dose topical MMC for PAM with atypia may be associated with a relatively
      high incidence of LSCD. Mitomycin C concentration and treatment regimen should be
      reevaluated to improve the safety of this treatment protocol.

PMID- 20060168
TI  - Orbital cysticercosis: clinical manifestations, diagnosis, management, and
      outcome.
AB  - PURPOSE: To describe the clinical manifestations, diagnosis, management, and
      outcome of orbital cysticercosis in a tertiary eye care center in Southern India.
      DESIGN: Retrospective observational case series. PARTICIPANTS: A total of 171
      patients with orbital cysticercosis. METHODS: Retrospective case series involving
      consecutive patients with orbital cysticercosis from March 1990 to December 2001.
      MAIN OUTCOME MEASURES: Clinical resolution and significant residual deficit.
      RESULTS: The median age at presentation was 13 years (range 2-65 years), and 93
      patients (54.4%) were male. The 3 main symptoms at presentation were periocular
      swelling (38%), proptosis (24%), and ptosis (14%) with a median duration of 2
      (range 0-24) months. The 3 main signs at presentation included ocular motility
      restriction (64.3%), proptosis (44.4%), and diplopia (36.8%). The cyst locations
      in the decreasing order of frequency were anterior orbit (69%), subconjunctival
      space (24.6%), posterior orbit (5.8%), and the eyelid (0.6%). In all, 80.7% of
      patients had cysts in relation to an extraocular muscle. The superior rectus
      (33.3%) was the most commonly involved extraocular muscle. Contact B-scan
      ultrasonography was diagnostic of cysticercosis in 84.4% of patients. Orbital
      cysticercosis was managed medically in 158 of 166 patients. Although 149 patients
      received a combination of oral albendazole and prednisolone, 1 patient received
      oral albendazole alone, 7 patients received oral prednisolone alone, and 1
      patient received oral praziquantel. Surgery was performed in 8 patients. Clinical
      resolution was seen in 128 of 138 patients (92.8%) at 1 month and 81 of 85
      patients (95.3%) at 3 months. A significant residual deficit was present in 29 of
      138 patients (21.0%) at the final follow-up and included proptosis in 7 patients,
      ptosis in 6 patients, ocular motility restriction in 3 patients, diplopia in 2
      patients, strabismus in 2 patients, and a combination of the above in 9 patients.
      CONCLUSIONS: Orbital cysticercosis is a common clinical condition in the
      developing world. It typically affects young individuals and has a wide spectrum
      of clinical manifestations. Both B-scan ultrasonography and computed tomography
      scan are useful in confirming the diagnosis. Despite resolution of cysticercosis
      with medical management, a significant proportion of patients may have residual
      functional deficits.

PMID- 20060169
TI  - On the bioreactivity of triorganotin aminobenzoates. Investigation of trialkyl
      and triarylyltin(IV) esters of 3-amino and 4-aminobenzoic acids.
AB  - The synthesis and study of trimethyl-, tributyl- and triphenyltin esters of the 3
      and 4-aminobenzoic acids are reported. The triorganotin derivatives are
      characterized by elemental analyses, FT-IR and solution (1)H and (13)C NMR
      spectra. The structure of the trimethyltin 4-aminobenzoate is solved by X-ray
      diffraction and proves to be polymeric in nature with bridging carboxylates and
      trigonal bipyramidal tin(IV) environment. However, all the compounds become
      monomeric in solution with a tetrahedral tin coordination environment in
      chloroform and trigonal bipyramidal in DMSO due to coordination of the solvent as
      the NMR spectra have revealed. The compounds exhibit variable cytotoxic activity
      when tested against Kappa562 myelogenous leukaemia, HeLa cervical cancer and
      HepG2 hepatocellular carcinoma cell lines, with the butyl derivatives being the
      more effective and the methyl ones the less. Interestingly, their antibacterial
      action was significantly lower when tested against Escherichia coli, while not
      appreciable direct interaction with DNA has been observed. The above observations
      account for a mode of action that may be related to their potential interaction
      with cell membranes and the subsequent inhibition of various signaling processes.

PMID- 20060170
TI  - Sucking patterns in fullterm infants between birth and 10 weeks of age.
AB  - OBJECTIVE: Coordinating sucking, swallowing and breathing to achieve effective
      sucking is a complex process and even though sucking is essential for nutrition,
      little is known about sucking patterns after birth. Our objective was to study
      sucking patterns in healthy fullterm infants and to describe the age-specific
      variations. METHOD: We studied the sucking patterns of 30 healthy, fullterm
      infants longitudinally from 2 or 3 days after birth to 10 weeks of age. During
      this time we recorded five to seven feeding episodes that we assessed off-line
      with the Neonatal Oral-Motor Assessment Scale (NOMAS). RESULTS: We found a normal
      sucking pattern on the second or third day after birth in 27 out of 30 infants.
      During the following weeks we found abnormal sucking patterns in 23 out of 171
      feeding episodes (14%) and normal patterns in 148 episodes (86%). Altogether,
      between 38 and 50 weeks' postmenstrual age (10 weeks after birth), 10 infants
      displayed a deviating, arrhythmical sucking pattern. Dysfunctional sucking
      patterns and problems of coordinating sucking, swallowing and breathing did not
      occur. Birth weight, gestational age, type of labour and gender did not influence
      sucking patterns. Arrhythmical sucking was seen more often in bottle-fed infants.
      CONCLUSION: Our study demonstrated that practically all healthy fullterm infants
      started off with a normal sucking pattern soon after birth. One-third of the
      infants displayed one or more deviating episodes up to the age of 10 weeks. Apart
      from bottle-feeding, no other factors were found that influenced sucking
      patterns.

PMID- 20060171
TI  - Suicide in patients treated for obsessive-compulsive disorder: a prospective
      follow-up study.
AB  - BACKGROUND: To describe the occurrence of persistent suicidal ideation and
      suicide attempts in a sample of obsessive-compulsive patients followed-up
      prospectively during 1 to 6years, and to determine the existence of predictors of
      suicide behavior. METHOD: Two hundred and eighteen outpatients with DSM-IV OCD,
      recruited from a specialized OCD Unit in Barcelona, Spain, between February 1998
      and December 2007, were included in the study. Suicide ideation was assessed by
      item 3 of the Hamilton Depression Rating Scale. Suicide attempts were evaluated
      by the Beck Suicide Intent Scale. Patients with and without persistent suicidal
      thoughts and suicide attempters and non-attempters were compared on
      sociodemographic and clinical variables. A Cox proportional hazards regression
      analysis was used to estimate potential predictors of suicide. RESULTS: Patients
      completed a mean follow-up period of treatment of 4.1years (SD: 1.7; range: 1
      6years). During this period, eighteen patients (8.2%) reported persistent
      suicidal ideation, two patients (0.91%) committed suicide and 11 (5.0%) attempted
      suicide. Being unmarried, presenting higher basal scores in the HDRS, current or
      previous history of affective disorders and symmetry/ordering obsessions were
      independently associated with suicidal behaviors. LIMITATIONS: Patients were
      recruited from a specialized OCD clinic and received exhaustive treatment.
      Influence of variables including social support, life events, hopelessness and
      substance abuse/dependence was not assessed. CONCLUSIONS: Suicide behavior is not
      a highly common phenomenon in OCD, but it should not be disregarded, especially
      in unmarried patients, with comorbid depression and symmetry/ordering obsessions
      and compulsions, who appear to be at a greater risk for suicide acts.

PMID- 20060172
TI  - Electroconvulsive therapy-induced persistent retrograde amnesia: could it be
      minimised by ketamine or other pharmacological approaches?
AB  - BACKGROUND: Certain pharmacological agents administered during electroconvulsive
      therapy may have the potential to prevent persistent retrograde amnesia induced
      during electroconvulsive therapy. This review examines mechanisms for
      electroconvulsive therapy-induced retrograde amnesia, and evaluates the
      suitability of the anaesthetic ketamine for preventing this amnestic outcome.
      METHODS: A review of human studies, animal models and theoretical models in light
      of memory dysfunction following electroconvulsive therapy was conducted. MEDLINE
      was searched from 1950 to April 2009 using the MeSH terms "electroconvulsive
      therapy", "memory", "memory short term", "memory disorders", "excitatory amino
      acid antagonists", and "ketamine". PREMEDLINE was searched using the terms
      "electroconvulsive therapy", "amnesia" and "ketamine". Additional keyword and
      reference list searches were performed. No language, date constraints or article
      type constraints were used. RESULTS: Disruption of long term potentiation as a
      mechanism for electroconvulsive therapy-induced retrograde amnesia is well
      supported. Based on this putative mechanism, an N-methyl-D-aspartate receptor
      antagonist would appear suitable for preventing the retrograde amnesia. Available
      evidence in animals and humans supports the prediction that ketamine, an
      anaesthetic agent and N-methyl-D-aspartate receptor antagonist, could effectively
      prevent electroconvulsive therapy-induced persistent retrograde amnesia. Whilst
      there are concerns about the use of ketamine with electroconvulsive therapy, such
      as possible psychotomimetic effects, on balance this anaesthetic agent may
      improve or hasten clinical response to electroconvulsive therapy. CONCLUSIONS: A
      clinical trial is warranted to determine if ketamine anaesthesia during
      electroconvulsive therapy can lessen persistent retrograde amnesia and improve
      therapeutic response. Electroconvulsive therapy with ketamine anaesthesia may
      provide effective antidepressant action with minimal side effects.

PMID- 20060173
TI  - The utility of Mood Disorder Questionnaire for the detection of bipolar diathesis
      in treatment-resistant depression.
AB  - BACKGROUND: Treatment-resistant depression is a heterogeneous entity. There are
      many variables associated with poor response to antidepressants, one of which is
      missed bipolarity. Therefore, the present study investigated the bipolar
      diathesis between patients with treatment-resistant (TR) depression and non
      treatment-resistant (NTR) depression as assessed with the Mood Disorder
      Questionnaire (MDQ). METHOD: The population studied included 1051 patients
      diagnosed with single or recurrent major depressive disorder. They were
      classified into a non-treatment-resistant group (481 patients) and a treatment
      resistant group (570 patients). The psychiatrist, using information from the
      patient's medical history, psychiatric examination and available documentation,
      assessed each eligible patient. The symptoms of bipolarity were additionally
      assessed by the Mood Disorder Questionnaire. RESULTS: A positive screen on the
      MDQ defined as endorsement of at least 6 of the 13 yes or no questions was an
      independent risk factor for treatment resistance.The total MDQ score was
      significantly higher in TR vs NTR (4.33 vs 2.66 points p<0.001) and the
      percentage of patients screened positive was significantly higher in TR than in
      NTR (13.7% vs 5.6% p<0.001). Factor analysis resulted in 2 factors with
      eigenvalues >1 explaining 91.5% of total variance. CONCLUSIONS: Using the MDQ
      scale we confirmed the association between bipolarity and worse response to
      antidepressant drugs in patients with major depressive disorder.

PMID- 20060174
TI  - The role of valproate in metabolic disturbances in bipolar disorder patients.
AB  - BACKGROUND: Our previous report showed that patients with bipolar disorder (BD)
      have higher prevalence of hypertriglyceridemia, low high-density lipoprotein
      cholesterol (HDL) and obesity in Taiwan. To confirm whether the metabolic
      disturbances is associated with the disease itself or the medications used for
      treating BD, we further compared the metabolic status among the valproate (VPA)
      treated BD patients, drug-free BD patients and healthy controls in Taiwan.
      METHOD: This cross-sectional study included 119 healthy controls and 77 BD
      patients diagnosed according to the DSMIV-TR criteria in a university hospital.
      Among the diseased group, 25 remitted BD patients were drug-free (BD-F), and 52
      of them were treated with VPA (BD-VPA). Their body mass index (BMI), plasma
      glucose levels and plasma lipid profiles were measured. RESULTS: Plasma fasting
      glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein
      cholesterol, and low-density lipoprotein cholesterol (LDL) levels were
      significantly different among BD-VPA, the BD-F, and the healthy control groups.
      Valproate treatment was associated with significant higher plasma insulin,
      triglyceride, and BMI levels as well as lower fasting glucose and HDL levels.
      However, these biochemical indexes did not differ significantly between the BD-F
      and the healthy control groups. CONCLUSION: These results provide further
      evidence that VPA treatment for BD may increase the risk of metabolic
      disturbances. The risk may be reduced after discontinuing VPA medication.

PMID- 20060175
TI  - Receptor heteromerization and drug discovery.
AB  - G-protein-coupled receptors (GPCRs) are membrane proteins that convert
      extracellular information into intracellular signals. They are involved in many
      biological processes and therefore represent powerful targets to modulate
      physiological and pathological states. Recent studies have demonstrated that GPCR
      activity is regulated by several mechanisms. Among these, protein-protein
      interactions (and in particular interactions with other receptors leading to
      heteromerization) has been shown to have an important role in modulating GPCR
      function. This has expanded their repertoire of signaling and added a new level
      of regulation to their physiological roles. Emerging studies provide evidence for
      tissue-specific and disease-specific receptor heteromerization. This suggests
      that heteromers represent novel drug targets for the identification of selective
      compounds with potentially fewer side-effects.

PMID- 20060176
TI  - Induction of oxidative stress and apoptosis by silver nanoparticles in the liver
      of adult zebrafish.
AB  - Silver nanoparticles (AgNPs) may induce deleterious effects in aquatic life on
      environmental release. The hepatotoxicity of AgNPs was assessed in the liver of
      adult zebrafish, with the aim of studying the roles of oxidative damage and
      apoptosis. Zebrafish were exposed to an AgNP solution in which free Ag+ ions were
      absent at the time of treatment. However, the metal-sensitive metallothionein 2
      (MT2) mRNA was induced in the liver tissues of AgNP-treated zebrafish, suggesting
      that Ag+ ions were released from AgNPs after treatment. It is also possible that
      MT2 mRNA was induced in the liver tissues by AgNP-generated free radicals. A
      number of cellular alterations including disruption of hepatic cell cords and
      apoptotic changes were observed in histological analysis of the liver tissues.
      The levels of malondialdehyde, a byproduct of cellular lipid peroxidation, and
      total glutathione were increased in the tissues after treatment with AgNPs. The
      mRNA levels of the oxyradical-scavenging enzymes catalase and glutathione
      peroxidase 1a were reduced in the tissues. AgNP treatment induced DNA damage, as
      demonstrated by analysis with the double-strand break marker gamma-H2AX and the
      expression of p53 protein in liver tissues. In addition, the p53-related pro
      apoptotic genes Bax, Noxa, and p21 were upregulated after treatment with AgNPs.
      These data suggest that oxidative stress and apoptosis are associated with AgNP
      toxicity in the liver of adult zebrafish.

PMID- 20060177
TI  - Genomics in Aquatic Toxicology.

PMID- 20060178
TI  - Office vs. ambulatory control of hypertension in CHD patients: response to the
      letter "When office blood pressure measurement is not enough" by Barrios and
      colleagues.

PMID- 20060179
TI  - Enhanced activity and subcellular redistribution of myocardial hexokinase after
      acute myocardial infarction.
AB  - BACKGROUND: Hexokinase (HK) is known to possess both anti-oxidant and anti
      apoptotic properties. This study investigated the behavior of myocardial HK in
      response to myocardial infarction (MI). METHODS: Adult male Wistar rats with
      various degrees of MI after coronary ligation were examined 4 weeks after
      operation and were divided dichotomously into small and large MI groups. The
      activity and subcellular distribution of HK in the non-infarcted myocardium were
      determined. In parallel, myocardial oxidative stress determined using aconitase
      activity and malondialdehyde content, and left ventricular function using
      echocardiography were studied. RESULTS: In the mitochondria and the cytosol, HK
      activity was enhanced after MI and paralleled the increases in oxidative stress
      and left ventricular end-diastolic dimension (LVEDD). The enhancement in HK
      activity varied between subcellular compartments and resulted in an increase in
      the ratio of cytosol to whole-cell HK activity, which was proportional to
      oxidative stress and LVEDD. CONCLUSIONS: The activities of HK in all subcellular
      fractions are enhanced in response to MI. However, enhanced proportion of
      cytosolic HK relative to whole-cell HK activity is associated with higher
      oxidative stress and LVEDD, suggesting that altered myocardial HK activity and
      subcellular redistribution might be involved in the pathogenesis of postinfarct
      heart failure.

PMID- 20060180
TI  - The effect of age in the cardiac MRI evaluation of the athlete's heart.
AB  - PURPOSE: Increasing age is accompanied by a higher risk of sports-related death,
      especially from coronary disease and cardiomyopathies. It is unclear if the
      mature athlete's heart differs from young athletes. Our aim was to assess the
      effect of age on ventricular volumes and wall-mass. We also established maximum
      cardiac MRI (CMR) reference values in mature athletes to facilitate
      differentiation from cardiomyopathy. METHODS: 143 healthy persons aged 40-60
      years (mean age 49+/-6 years [+/-SD], 39% women) underwent CMR: 78 athletes
      (exercising 9-18 h/week), and 65 age and gender matched non-athletes (<=3
      h/week). From a larger study, cardiac MRI data of 195 healthy persons aged 18-39
      years (mean age 28+/-6, 48% women) were included for statistical analysis: 81
      athletes and 114 matched non-athletes. RESULTS: With multivariate analysis, age
      only has limited effect on ventricular volumes (LV 1%, RV 3%) and wall-mass
      (0.01%). Only athletes show significant decrease in right and left ventricular
      volumes and LV-mass with increasing age (p<0.05). RV wall-mass remains unaffected
      by age. Ventricular diameters, volumes and wall-mass are significantly lower in
      mature athletes compared to young athletes, and significantly higher compared to
      mature non-athlete controls (p<0.05). CONCLUSIONS: Only athletes show a
      significant decrease in ventricular volumes and LV wall-mass with increasing age,
      which probably reflects decreasing training intensity rather than the effect of
      age. Mature athletes form a distinct group requiring separate reference values as
      they have significantly lower ventricular volumes and wall-mass as compared to
      young athletes, however, still significantly higher values than mature non
      athletes.

PMID- 20060181
TI  - Changes in cardiovascular hospitalization and comorbidity of heart failure in the
      United States: findings from the National Hospital Discharge Surveys 1980-2006.
AB  - OBJECTIVE: This study aimed to update the long-term trend of coronary heart
      disease (CHD), cerebrovascular disease (CBVD), and heart failure (HF)
      hospitalization rates and HF comorbidity among adults aged 65 and older in the
      United States. METHODS: Data from the National Hospital Discharge Surveys between
      1980 and 2006 were used. CHD, CBVD, and HF were defined using the principal
      (first-listed) diagnosis of disease at hospital discharge according to the ICD-9
      CM code. Census estimated population data (2000) were used to estimate age and
      gender-specific hospitalization rates. RESULTS: Age-adjusted CHD and CBVD
      hospitalization rates have significantly decreased between 1980 and 2006, with an
      estimated annual decrease rate of 2.24% for CHD and 1.55% for CBVD in men, and
      2.36% for CHD and 1.34% for CBVD in women. However, the absolute numbers of CHD
      and CBVD hospitalization continued to increase partly because of the aging
      population. Furthermore, HF hospitalization rates have significantly increased
      with an estimated annual rate increase of 1.20% in men and 1.55% in women between
      1980 and 2006. Of six selected co-morbidities, about 50% in men and 40% in women
      with HF had a coexisting disease of CHD, followed by chronic obstructive
      pulmonary disease, diabetes mellitus, renal failure, and pneumonia. CONCLUSIONS:
      While the burden of CHD and CBVD remains the major public health problem, HF has
      emerged as a new challenge in cardiovascular disease control, characterized by
      increased trends of HF hospitalization and increased comorbidities from major
      diseases.

PMID- 20060182
TI  - Differential protein biomarker expression and their time-course in patients with
      a spectrum of stable and unstable coronary syndromes in the Integrated Biomarker
      and Imaging Study-1 (IBIS-1).
AB  - OBJECTIVES: IBIS-1 was a pilot study undertaken to correlate coronary imaging
      with circulating biomarker expression in patients with stable angina, unstable
      angina and acute myocardial infarction. We hypothesized that patients at high
      risk of future events could be identified in the future by a combination of high
      risk plaque features by plaque echogenicity and palpography and a set of
      circulating blood biomarkers. RESULTS AND METHODS: We assessed the expression of
      conventional biomarkers and novel marker protein microarray (170 analytes) over 6
      months. There were no strong correlations observed between conventional
      biomarkers and coronary imaging in non-culprit artery. Proteomic microarray was
      performed in 66 patients. Seventy eight (45%) analytes showed dynamic changes
      over time. Using hierarchical clustering and principal component analysis two
      subsets of biomarkers were identified: initial up-regulation and decrease over
      time (D-dimer, hepatocyte growth factor, CXCL9/MIG, platelet factor 4/CXCL4,
      CTACK, C-6 Kine, follistatin, and FGF-7) and the opposite increase (PAI-1- anti
      apoptotic protein and I-309--chemokine induced on the human endothelium by
      Lp(a)). CONCLUSIONS: Proteomic analysis identifies dynamic patterns in
      circulating biomarkers in a wide range of patients with coronary artery disease.
      Further large natural history studies are needed to better define multibiomarker
      sets for identification of patients at risk of future CV events.

PMID- 20060183
TI  - Long-term clinical outcomes after drug eluting stent implantation in women with
      de novo coronary lesions. Results from the REAL (REgistro Regionale
      AngiopLastiche Emilia-Romagna) multicenter registry.
AB  - BACKGROUND: The long-term effectiveness of drug eluting stents (DESs) in a real
      world setting of female patients is currently unclear. METHODS AND RESULTS: We
      analyzed long-term follow-up (up to 3 years) data from all female patients with
      de novo lesions enrolled in a prospective web-based multicenter registry (REAL
      Registry; study period, July 2002-June 2006) including all 15 hospitals
      performing PCI in the Emilia-Romagna region of Italy. Among the 3549 women
      without ST elevation myocardial infarction, 2434 were treated with BMSs alone and
      1115 with DESs alone. At 3 years, use of DESs was associated with a lower
      propensity score adjusted incidence of MACE [cardiac mortality, non-fatal
      myocardial infarction and target vessel revascularization (TVR); 19.5% vs. 24.4%;
      HR 0.75, p=0.006)] and TVR (11.6% vs. 15.6%; HR 0.68, p=0.004) compared with
      BMSs. No difference was apparent in terms of adjusted 3-year cardiac mortality or
      myocardial infarction. Nevertheless, after the first 6 months of follow-up, a non
      significantly increased risk of myocardial infarction and stent thrombosis was
      found in the DES group. CONCLUSIONS: In this real-world female registry, the use
      of DESs was associated with a 3-year reduction of TVR and MACE in comparison with
      the use of BMSs. However, the observed (non-significant) increment of late AMI
      makes performing larger studies to clarify the long-term safety of DESs
      mandatory.

PMID- 20060184
TI  - Hyperkalaemia, pseudohyperkalaemia and electrocardiographic correlates.

PMID- 20060185
TI  - Angiotensin converting enzyme 2 gene expression increased compensatory for left
      ventricular remodeling in patients with end-stage heart failure.
AB  - It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of
      ACE, has direct effects on cardiac function. However, the role of ACE2 in the
      development of human heart failure is not fully understood. We evaluated the
      expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14
      patients with end-stage heart failure. The amount of ACE2 mRNA positively
      correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01)
      but did not significantly correlate with LV ejection fraction or plasma brain
      natriuretic peptide levels. In conclusion, our data show that the up-regulation
      of the ACE2 gene in the LV myocardium of patients with severe heart failure was
      associated with the degree of LV dilatation and may thereby constitute an
      important adaptive mechanism to retard the progression of adverse LV remodeling.

PMID- 20060186
TI  - Dose recalculation in megavoltage cone-beam CT for treatment evaluation: removal
      of cupping and truncation artefacts in scans of the thorax and abdomen.
AB  - PURPOSE: To correct megavoltage cone-beam CT (MVCBCT) images of the thorax and
      abdomen for cupping and truncation artefacts to reconstruct the 3D-delivered dose
      distribution for treatment evaluation. MATERIALS AND METHODS: MVCBCT scans of
      three phantoms, three lung and two rectal cancer patients were acquired. The cone
      beam projection images were iteratively corrected for cupping and truncation
      artefacts and the resulting primary transmission was used for cone-beam
      reconstruction. The reconstructed scans were merged into the planning CT scan
      (MVCBCT+). Dose distributions of clinical IMRT, stereotactic and conformal
      treatment plans were recalculated on the uncorrected and corrected MVCBCT+ scans
      using the treatment planning system and compared to the planned dose
      distribution. RESULTS: The dose distributions on the corrected MVCBCT+ of the
      phantoms were accurate for 99% of the voxels within 2% or 2mm. Using this method
      the errors in mean GTV dose reduced from about 10% to 1% for the patients.
      CONCLUSIONS: The method corrects cupping and truncation artefacts in cone-beam
      scans of the thorax and abdomen in addition to head-and-neck (demonstrated
      previously). The corrected scans can be used to calculate the influence of
      anatomical changes on the 3D-delivered dose distribution.

PMID- 20060187
TI  - Quantification of Penicillium camemberti and P. roqueforti mycelium by real-time
      PCR to assess their growth dynamics during ripening cheese.
AB  - Real-time PCR has been applied to quantify mycelium of Penicillium camemberti and
      Penicillium roqueforti during ripening of model cheese curd and surface mould
      ripened cheeses. Total fungal DNA was first validated as an indicator of mycelial
      biomass in pure liquid culture and then in model curds at different stages of
      ripening. To imitate cheese matrix effects, DNA was extracted from curd mixed
      with known amounts of fresh mycelium of P. camemberti or P. roqueforti and was
      used as biomass standards for further quantitative real-time PCR. Mycelial mass
      per cheese (mg/g) was then directly obtained from fluorescence data. In model
      cheese curd, mycelial mass of P. camemberti increased from 2.8 at d4 to 596 mg/g
      at d11 whereas P. roqueforti increased from 0.3 to 6.3 mg/g during the same
      period. P. camemberti showed a fast development in Coulommiers from d2 to d9 (66
      to 119 mg/g) and a 100-fold increase in Carre (0.85 to 85 mg/g). While mycelial
      biomass reached a maximum at d9 in Coulommiers, it still developed in Carre until
      d45. For the first time, cheese manufacturers have a powerful technique to
      monitor mycelial growth dynamics of their fungal cultures, which represents an
      important step for controlling cheese making.

PMID- 20060188
TI  - The antimicrobial effect of oregano essential oil, nisin and their combination
      against Salmonella Enteritidis in minced sheep meat during refrigerated storage.
AB  - The antimicrobial effect of oregano essential oil (EO) at 0.6 or 0.9%, nisin at
      500 or 1000 IU/g, and their combination against Salmonella Enteritidis was
      studied in minced sheep meat during storage at 4 degrees or 10 degrees C for 12
      days. Sensory evaluation showed that the addition of oregano EO at 0.6 or 0.9% in
      minced sheep meat was organoleptically acceptable, and attribute scores were
      higher for the EO at 0.6 than 0.9%. According to compositional analysis of the
      oregano EO, the phenols carvacrol (80.15%) and thymol (4.82%) were the
      predominant components. Treatment of minced sheep meat with nisin at 500 or 1000
      IU/g, proved insufficient to act against S. Enteritidis. The combination of the
      oregano EO at 0.6% with nisin at 500 IU/g showed stronger antimicrobial activity
      against S. Enteritidis than the oregano EO at 0.6% but lower than the combination
      with nisin at 1000 IU/g, which in turn was lower than that of the oregano EO at
      0.9%. In its turn, oregano EO at 0.9% showed lower antimicrobial activity than
      its combinations with nisin at 500 or 1000 IU/g, which showed a bactericidal
      effect against the pathogen. The inhibition percentages of all treatments against
      S. Enteritidis at 10 degrees C were higher than those at 4 degrees C.

PMID- 20060189
TI  - A real-time PCR method for the detection of Salmonella enterica from food using a
      target sequence identified by comparative genomic analysis.
AB  - A 5'-nuclease real-time PCR assay using a minor groove binding probe was
      developed for the detection of Salmonella enterica from artificially contaminated
      foods. S. enterica-specific sequences were identified by a comparative genomic
      approach. Several species-specific target sequences were evaluated for
      specificity. A real-time PCR assay was developed targeting a nucleotide sequence
      within the putative type III secretion ATP synthase gene (ssaN). An internal
      amplification control (IAC) probe was designed by randomly shuffling the target
      probe sequence and a single-stranded oligonucleotide was synthesized to serve as
      an IAC. The assay demonstrated 100% inclusivity for the 40 Salmonella strains
      tested and 100% exclusivity for 24 non-Salmonella strains. The detection limit of
      the real-time PCR assay was 41.2 fg/PCR with Salmonella Typhimurium genomic DNA
      and 18.6 fg/PCR using Salmonella Enteritidis genomic DNA; 8 and 4 genome
      equivalents, respectively. In the presence of a natural background flora derived
      from chicken meat enrichment cultures, the sample preparation and PCR method were
      capable of detecting as few as 130 Salmonella cfu/mL. Using the developed real
      time PCR method to detect Salmonella in artificially contaminated chicken, liquid
      egg and peanut butter samples, as few as 1 cfu/10 g of sample was detectable
      after a brief (6h) non-selective culture enrichment.

PMID- 20060191
TI  - The effect of mosapride (5HT-4 receptor agonist) on insulin sensitivity and GLUT4
      translocation.
AB  - AIMS: We investigated the effect of mosapride, 5HT-4 (5-hydroxytryptamine)
      agonist, on blood glucose level and insulin sensitivity in subjects with impaired
      glucose tolerance (IGT) and conducted an in vitro study to evaluate the action
      mechanism. METHODS: Thirty IGT patients were randomly assigned to receive either
      mosapride or placebo for 2 weeks. Biochemical profiles and insulin sensitivity
      index from euglycemic hyperinsulinemic clamp test were assessed before and after
      treatment. In cultured myotubes from human skeletal muscle cells, insulin- and
      mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were
      determined. RESULTS: After 2 weeks of treatment with mosapride, glucose disposal
      rates were significantly increased up to those of control (mosapride 5.47+/-1.72
      vs 7.06+/-2.13, P=0.004, placebo 5.42+/-1.85 vs 5.23+/-1.53mgkg(-1)min(-1)).
      Fasting plasma glucose (FPG) and insulin levels were decreased. Mosapride
      increased the contents of GLUT4 in plasma membrane representing the increased
      recruitment of glucose transporters from intracellular pool. While insulin
      treatment on human skeletal muscle cell resulted in an increased tyrosine
      phosphorylation of IRS-1, mosapride did not have any effect. CONCLUSIONS:
      Mosapride is effective in decreasing FPG without stimulating insulin secretion in
      IGT subjects, possibly by inducing GLUT4 translocation in skeletal muscles.

PMID- 20060190
TI  - Glycemic control and its correlates in patients with diabetes in Venezuela:
      results from a nationwide survey.
AB  - AIMS: To determine the prevalence of inadequate glycemic control and its
      correlates in a large multicenter survey of Venezuelan patients with diabetes.
      METHODS: A cross-sectional study in a sample of adult patients with diabetes,
      attending health centers in Venezuela. Information about diabetes, current
      medications, complications, and diet were obtained by trained interviewers, using
      a standardized questionnaire. HbA(1c) was measured by high-performance liquid
      chromatography in a central laboratory. Patients with HbA(1c) >or=7% were
      considered to have inadequate glycemic control. RESULTS: Overall 4075 patients
      were surveyed, 349(8.6%) with type 1 diabetes (T1D) and 3726(91.4%) with type 2
      diabetes(T2D). Subjects' mean age was 58 years, and 65% were female. The
      prevalence of inadequate glycemic control was 76%. Poor glycemic control was more
      common in T1D patients (87%) than in those with T2D(75%), p<10(-4). Satisfaction
      with current diabetes treatment was associated with improved glycemic control
      among non-insulin-treated patients with T2D, but gender, multi-professional care,
      and participation in a diabetes education program were not. CONCLUSIONS: Despite
      clinical evidence supporting tight control of diabetes, few diabetic patients in
      Venezuela met recommended glycemic control targets. This may contribute to
      increased rates of diabetic complications. Our findings support the public health
      message of implementation of early, aggressive management of diabetes.

PMID- 20060192
TI  - Effects of short-term therapy with different insulin secretagogues on glucose
      metabolism, lipid parameters and oxidative stress in newly diagnosed Type 2
      Diabetes Mellitus.
AB  - AIM: To compare effects of three different insulin secretagogues on early-phase
      insulin secretion, metabolism of glucose and lipids, and lipid peroxidation in
      newly diagnosed Type 2 Diabetes Mellitus (T2DM). METHODS: Totally 60 newly
      diagnosed T2DM outpatients were randomized to three groups with 1-month
      monotherapy of repaglinide (Rg), glimepiride (Gm) or gliclazide MR (Gli),
      respectively. Some indexes of early-phase insulin secretion, glucose, lipids, and
      lipid peroxidation were inspected. RESULTS: Fasting plasma glucose (FPG),
      glycosylated hemoglobin (HbA(1c)) and fructosamine (FA) were improved in all
      groups similarly (p>0.05). Rg group was with the highest early-phase insulin
      secretion index (DeltaI30/DeltaG30) (p=0.026), lower mean amplitude of glycaemic
      excursion (MAGE) (p<0.05), lowest mean peak value of post-lunch glucose
      (p=0.043), and lowest postprandial triglyceride (TG) (p=0.039). Postprandial free
      fatty acid (FFA) was lower after Rg and Gli treatment (p<0.05). Serum 8-iso
      prostaglandin F(2alpha) (8-iso PGF(2alpha)) was improved in all groups, but the
      improvement showed statistically significant only in Rg group (p=0.04).
      CONCLUSION: Rg, Gm and Gli can all decrease blood glucose effectively in newly
      diagnosed T2DM patients, while Rg performs outstandingly in the aspects of
      improving early-phase insulin secretion, glucose excursion, postprandial lipids
      and 8-iso PGF(2alpha).

PMID- 20060193
TI  - Perceived barriers to utilization of maternal health services in rural Cambodia.
AB  - OBJECTIVE: The aim of this study was to identify the underlying causes of
      Cambodian women's non-use of maternal health services provided by skilled birth
      attendants. METHOD: A qualitative study of 66 reproductive-age women was
      conducted in Kampong Cham Province, Cambodia. Data were collected through 30 semi
      structured interviews and 6 focus groups. RESULTS: We identified 5 barriers to
      the utilization of maternal health services: (i) financial barriers; (ii)
      physical barriers; (iii) cognitive barriers; (iv) organizational barriers; and
      (v) psychological and socio-cultural barriers. CONCLUSIONS: The Cambodian
      Ministry of Health and its development partners should take these barriers into
      account when promoting the use of maternal health services. These barriers should
      be addressed proactively. A successful approach to increasing use of maternal
      health services should involve changes to both service programs and public
      education.

PMID- 20060194
TI  - Prognostic significance of matrix metalloproteinase-1 levels in peripheral plasma
      and tumour tissues of lung cancer patients.
AB  - Matrix metalloproteinase-1 (MMP-1) participates in a variety of physiological and
      pathological processes. We previously found that MMP-1 was one of the lung cancer
      related proteins detectable in peripheral blood. To validate our preliminary
      observations and explore the clinical significance of MMP-1 for lung cancer
      further, we carried out the present study. The concentrations of MMP-1 in
      circulating plasma specimens of 170 lung cancer patients and 70 healthy
      individuals were measured by an enzyme-linked immunosorbance assay. The
      expression status of the MMP-1 in archival tissue samples from 122 lung cancer
      patients was examined by immunohistochemical analysis. The correlation between
      the MMP-1 levels and prognosis of the lung cancer patients was then assessed
      statistically. Protein levels of MMP-1 were considerably raised in the plasma
      from lung cancer patients relative to those in healthy controls. The high plasma
      MMP-1 levels were associated with advanced-stage of the disease and significantly
      lower overall survival rate of the patients. Coincidently, MMP-1 protein
      extraordinarily overexpressed in the tumour tissues of lung cancer; and the up
      regulated MMP-1 was associated with the progression (including tumour size,
      staging and lymphatic invasion), especially with decreased survival rate of the
      patients. Statistic analysis revealed that MMP-1 protein levels had an
      independent influence on survival. MMP-1 levels were elevated in both tumour
      tissue and blood; the latter may serve as an independent predictor for survival
      of lung cancer patients. MMP-1 protein levels in plasma/serum thus represent a
      potential and clinically relevant biomarker for the prognosis of patients with
      lung cancers.

PMID- 20060195
TI  - Stereotactic body radiotherapy using real-time tumor tracking in octogenarians
      with non-small cell lung cancer.
AB  - As the incidence of stage I non-small cell lung cancer (NSCLC) increases among
      octogenarians and only selected patients are surgical candidates, an alternative
      treatment is necessary. This manuscript evaluates the overall survival, local
      tumor control rate, and treatment-related toxicity after stereotactic body
      radiotherapy (SBRT) in 38 octogenarians with stage I NSCLC. Treatment consisted
      of 45Gy (n=4) or 60Gy (n=25) in 3 fractions for patients with peripheral tumors.
      A risk adaptive schedule of 45-60Gy in 3-6 fractions was used for central (n=7)
      or large peripheral tumors (n=2). An overall survival rate of 65% at 1 year and
      44% at 2 years was achieved in octogenarians after SBRT. The local tumor control
      rate was excellent (100% at 2 years) and no grade 4 or 5 treatment-related
      toxicity occurred. Despite the high incidence of comorbidity in these
      octogenarians (Charlson score >or=5 in 16% of patients), an approach that merely
      provides supportive care cannot always be justified. SBRT offers octogenarians
      with stage I NSCLC a good treatment alternative.

PMID- 20060196
TI  - Acclimation of Norway spruce photosynthetic apparatus to the combined effect of
      high irradiance and temperature.
AB  - Diurnal courses of photosynthetic gas exchange parameters, chlorophyll a
      fluorescence characteristics and the de-epoxidation state of the xanthophyll
      cycle pigments (DEPS) were measured during the gradual acclimation of 4-year-old
      Norway spruce seedlings to different photosynthetic photon flux density (PPFD)
      and air temperature (T(air)) regimes, simulating cloudy days with moderate T(air)
      (LI, maximum PPFD 300 micromol m(-2)s(-1), T(air) range 15-25 degrees C), sunny
      days with moderate T(air) (HI, maximum PPFD 1000 micromol m(-2)s(-1), T(air)
      range 15-25 degrees C) and hot sunny days (HI-HT, maximum PPFD 1000 micromol m(
      2)s(-1), T(air) range 20-35 degrees C). The plants were acclimated inside a
      growth chamber and each acclimation regime lasted for 13d. Acclimation to HI
      conditions led to a strong depression of the net CO(2) assimilation rates (A(N)),
      particularly during noon and afternoon periods. Exposure to the HI-HT regime led
      to a further decrease of A(N) even during the morning period. Insufficient
      stomatal conductance was found to be the main reason for depressed A(N) under HI
      and HI-HT conditions. Only slight changes of the maximum photosystem II (PSII)
      photochemical efficiency (F(V)/F(M)), in the range of 0.78-0.82, supported the
      resistance of the Norway spruce photosynthetic apparatus against PSII
      photoinhibition during acclimation to both HI and HI-HT conditions. The HI plants
      showed increased content of xanthophyll cycle pigments (VAZ) and enhanced
      efficiency of thermal energy dissipation within PSII (D) that closely correlated
      with the increased DEPS. In contrast, acclimation to the HI-HT regime resulted in
      a slight reduction of VAZ content and significantly diminished D and DEPS values
      during the entire day in comparison with HI plants. These results indicate a
      minor role of the xanthophyll cycle-mediated thermal dissipation in PSII
      photoprotection under elevated temperatures. The different contributions of the
      thermal dissipation and non-assimilatory electron transport pathways in PSII
      photoprotection during acclimation of the Norway spruce photosynthetic apparatus
      to excess irradiance and heat stresses are discussed.

PMID- 20060197
TI  - [Cultural management of diagnosis announcement in ophthalmology].
AB  - There are important differences in the way cultures conceive diseases. The
      intercultural approach of diseases can enhance the ability of the medical staff
      to understand the patients' problems within their culture, to communicate medical
      explanations to the patients for better mutual comprehension, to alleviate
      patient's sufferings, to ensure compliance to follow up and treatment. We report
      the case of a multicultural approach for the announcement of a diagnosis of
      blindness for a baby with multiple diseases, in the course of visual
      electrophysiology clinics. This case shows the different possibilities of
      intercultural approach of diseases, with three levels of implication. At the
      first level we may acquire the knowledge of ethnologic tools to understand
      disease representations, types and causes that can be very different from the
      Western ones, in the patient's community. At the second level we may integrate
      cultural consciousness in the management of clinics. At the third level we may
      proceed to the cultural mediation of diseases. Practicing this intercultural
      approach of the patient develops the ethical part of the therapeutic
      relationship, it also provides the patients and the physicians better comfort,
      and better efficiency for prevention campaigns.

PMID- 20060198
TI  - The effect of removal of point-of-care fecal occult blood testing on performance
      of digital rectal examinations in the emergency department.
AB  - STUDY OBJECTIVE: We determine whether removing point-of-care fecal occult blood
      testing from the emergency department (ED) is associated with a decrease in
      documented digital rectal examinations. METHODS: We performed a retrospective
      observational chart review study examining documented digital rectal
      examinations, before and after removal of a point-of-care fecal occult blood
      test, on all adult patients who presented to our ED with chief complaints that
      were likely to warrant a fecal occult blood test (intervention-sensitive). We
      studied the 6 months immediately before and after switching from bedside fecal
      occult blood testing to immunohistochemical laboratory fecal occult blood
      testing. We compared the results with those from a similar cohort of patients who
      presented during the same period, with chief complaints that would warrant a
      digital rectal examination for reasons other than fecal occult blood test
      (intervention-insensitive). RESULTS: A total of 4,981 and 5,557 patients met our
      inclusion criteria during the before and after intervention periods,
      respectively. We observed an overall reduction of 10% (95% confidence interval
      [CI] 8% to 12%) in digital rectal examinations in patients with intervention
      sensitive chief complaints. The largest relative decreases in digital rectal
      examinations were observed in patients with chief complaints of abdominal pain,
      nausea/vomiting, and diarrhea. Smaller decreases were observed in
      gastrointestinal bleeding, constipation, and rectal problem. There was an overall
      reduction of 3% (95% CI 0% to 5%) in documented digital rectal examinations in
      intervention-insensitive chief complaints. After controlling for all covariates,
      digital rectal examinations decreased in the postintervention period for
      intervention-sensitive (odds ratio 0.44 [95% CI 0.39 to 0.50]) and, to a lesser
      extent, for intervention-insensitive (odds ratio 0.67 [95% CI 0.52 to 0.86])
      conditions. CONCLUSION: Removal of point-of-care fecal occult blood test from our
      ED was associated with a reduction in digital rectal examinations, particularly
      among chief complaints that may require fecal occult blood testing.

PMID- 20060199
TI  - Conservative management of transnasal intracranial injury.
AB  - The purpose of this study was to explore the conservative management for an
      unusual case of transnasal intracranial injury. A 3-year-old female child
      presenting with transnasal injuries after a domestic accident whereby she
      apparently fell while holding a large pair of scissors, which then penetrated her
      left nasal cavity, piercing her nasal cavity, ethmoid sinus, and skull base. The
      scissors were removed from her nasal cavity. The patient had scant cerebrospinal
      rhinorrhea and no other additional neurologic deficits noted at the time, as well
      as no long-term developmental deficits. This report highlights the occurrence of
      this rare condition. The role of radiologic studies such as computed tomographic
      scans and plain films in diagnosis and management of this case is affirmed. The
      strategy of minimally invasive treatment of this injury can be a reasonable
      treatment option.

PMID- 20060200
TI  - Neonatal dacryocele with endonasal cyst: revisiting the management.
AB  - PURPOSE: The aim of the study was to present a consecutive series of neonatal
      dacryocele with endonasal cyst diagnosed and treated in our institution and to
      compare our management regimen and outcome with those reported in the literature.
      METHODS: The study was conducted at a university-affiliated teaching hospital.
      Study population included 5 infants, ages 1 day to 1 month, with either
      noninfected or infected neonatal dacryocele with endonasal cyst. Management
      included antibiotic treatment (topical and/or systemic) and local lacrimal
      massage. When conservative treatment failed, endoscopic identification and
      incision of the endonasal cyst with subsequent lacrimal duct irrigation with
      fluorescein and antibiotics were carried out in the office. Main outcome measures
      included resolution of symptoms and recurrence rate. RESULTS: Between the years
      2003 and 2007, 5 infants were diagnosed and treated. All had unilateral
      dacryocele with endonasal cyst. Female-to-male ratio was 4:1. Age ranged from 1
      day to 1 month old. Three had dacryocystitis (60%) before treatment. None had
      symptoms of airway obstruction. One patient was successfully treated
      conservatively with firm massage by the ophthalmologist resulting in rupture of
      the endonasal cyst and did not require further treatment. Four patients were
      treated with a combined ophthalmology/otolaryngology surgical procedure. All
      patients were treated in an office setting without general anesthesia. One
      patient underwent computed tomographic imaging before treatment to confirm the
      diagnosis. Follow-up ranged from 1 month to 50 months with an average of 23
      months. Complete resolution was observed in all patients without recurrence and
      without complications. CONCLUSIONS: We report on the successful surgical
      treatment of neonatal dacryocele with endonasal cyst in an office setting without
      the use of general anesthesia, using endoscopic incision of the cyst and
      irrigation alone. The high success rate of this relatively benign office
      procedure encourages its use and further supports the approach of early surgical
      intervention, thus, helping to avoid infectious complications that can be severe
      at this age.

PMID- 20060202
TI  - New isatin derivatives with antioxidant activity.
AB  - The reaction between isatin and 2,5-dimethoxyaniline is described. The main
      product was identified as 3,3-bis(4-amino-2,5-dimethoxyphenyl)-1,3-dihydroindol-2
      one. The antioxidant activity of the compounds isolated was evaluated with two
      methods. Three published antitumor E-3-(2-chloro-3-indolylmethylene)1,3
      dihydroindol-2-ones entered the same tests to search whether they are endowed
      with antioxidant activity too. 3,3-Bis(4-amino-2,5-dimethoxyphenyl)-1,3
      dihydroindol-2-one and the three antitumor agents showed a good chemical
      antioxidant activity.

PMID- 20060203
TI  - Non-axial administration of fentanyl in childbirth: a review of the efficacy and
      safety of fentanyl for mother and neonate.
AB  - OBJECTIVE: to investigate the use of fentanyl for pain relief during childbirth
      administered by routes other than epidural or spinal (non-axial). In particular,
      aspects relating to the efficacy and safety of fentanyl for mother and neonate
      are explored. BACKGROUND: currently, pethidine is the most widely used
      intramuscular opioid for the relief of labour pain but has been shown to have
      numerous side-effects on the mother and neonate. An alternative opioid, fentanyl,
      has been shown to have fewer side-effects on both mother and neonate than
      pethidine. Therefore, its use during childbirth was examined in this literature
      review. REVIEW METHODS: a search of articles relating to the administration of
      fentanyl via non-axial routes was conducted using electronic databases, key
      journals and reference lists of selected research papers and reviews. RESULTS:
      only studies of IV administration were identified from the literature findings
      from showed that IV administered fentanyl appeared to be a safe, efficacious
      opioid when administered for pain relief in childbirth. Fentanyl is a short
      acting analgesic causing less sedation and nausea in adults than pethidine. In
      addition, no long-term fetal or neonatal effects of fentanyl were identified,
      with normal neonatal neurological and adaptive capacities at two hours and 24
      hours after birth supporting its safe use in childbirth. KEY CONCLUSION: in the
      studies identified, fentanyl was found to be efficacious, providing prompt
      analgesia with minimal side-effects to both mother and infant when administered
      intravenously (IV) during childbirth. In addition, no long-term fetal effects
      were found. RECOMMENDATIONS FOR FURTHER RESEARCH: there is a paucity of research
      relating to the maternal, fetal and neonatal effects of non-axial administered
      fentanyl other than that of IV. Further research should explore alternate routes
      of administration such as subcutaneous, sublingual and nasal which are less
      invasive and can be administered by midwives. IMPLICATION FOR PRACTICE: in
      confirming the safe use of non-axial administration of fentanyl during
      childbirth, benefits include midwives being able to offer women an alternative
      option for pain relief. Alternative routes, such as subcutaneous, can be managed
      by midwives through a standing order, potentially reducing the need for
      additional resources. In particular, this will benefit midwifery practice in
      rural and remote settings where resources and access to specialised services are
      limited.

PMID- 20060204
TI  - The sclerotic line: why it appears under knee replacements (a study based on the
      Oxford knee).
AB  - BACKGROUND: Radiolucent lines and sclerotic margins are often seen on knee
      radiographs taken a year or longer after knee replacement surgery. Histology has
      shown that the radiolucent zone is predominantly fibrocartilage and the sclerotic
      margin is lamellar bone. The reasons for their existence are not clearly
      understood. METHODS: A three-dimensional finite element model of the medial half
      of the proximal 75mm of a tibia implanted with a knee replacement was created and
      run over 365 iterations simulating 1year of in vivo post implant remodelling.
      After each iteration, new material properties were calculated for all elements of
      the model using established bone remodelling and tissue differentiation rules.
      For comparison with patient anteroposterior radiographs, "synthetic
      anteroposterior radiographs" were generated by reverse calculating radiographic
      densities from material properties of the model after 365 iterations. Von Mises
      stress of elements in the bone where the sclerotic line is usually seen were
      calculated after 365 iterations. These values were compared with the same
      entities assuming no remodelling. FINDINGS: The mean von Mises stress in the
      sclerotic region was higher when remodelling was assumed than when not,
      suggesting that the presence of the soft tissue (radiolucent line) increased the
      stress in the underlying bone. INTERPRETATION: The sclerotic line is caused by
      the stiffening of bone due to the relatively larger loads seen by the bone just
      beneath the soft tissue (radiolucent line) adjoining knee replacements.

PMID- 20060205
TI  - The association of IL-1beta, IL-2, and IL-6 gene polymorphisms with bone mineral
      density and osteoporosis in postmenopausal women.
AB  - OBJECTIVE: Osteoporosis is a common disorder with a strong genetic component. The
      genetics of osteoporosis impacts on the prediction, diagnosis, prognosis, and
      treatment of the disease. STUDY DESIGN: The aim of the present study was to
      examine associations between cytokine gene polymorphisms (IL-1beta, IL-2, IL-6)
      and bone mineral density (BMD) values in postmenopausal women. The study included
      226 postmenopausal women with a diagnosed BMD T-score lower than -2.5 SD (mean: 
      3.02+/-.053) and 224 postmenopausal women with a BMD T-score greater than -2.5 SD
      (mean: -1.33+/-0.51). RESULTS: Among the women with T-scores below -2.5 SD, the
      BMD values were significantly lower in the carriers of the IL-6 GG genotype
      compared with those with the CC and GC genotypes (0.70+/-0.38 vs. 0.73+/-0.25 and
      0.74+/-0.23 for the lumbar spine, 0.54+/-0.18 vs. 0.56+/-0.15 and 0.58+/-0.22 for
      the femoral neck). There were no statistically significant associations between
      the IL-1beta and IL-2 genotypes and BMD values in the group of women with T
      scores below -2.5 SD. CONCLUSION: The results of the present study suggest an
      association of the IL-6 -174 G/C polymorphism with osteoporosis in postmenopausal
      women.

PMID- 20060206
TI  - Structural changes induced in thionins by chloride anions as determined by
      molecular dynamics simulations.
AB  - Computational analysis of two membrane-permeabilizing peptides, barley alpha
      hordothionin and wheat beta-purothionin, revealed that anions can trigger dynamic
      and structural changes in the thionin antiparallel double alpha-helix core.
      Analysis of the molecular dynamics simulations demonstrated that anions induced
      unfolding of the alpha2 and alpha1 helices at the carboxyl ends which are located
      on the opposite ends of the alpha-helix core. An internalized water molecule was
      observed inside the unfolded alpha2 C-end. Strong interactions of anions with the
      R30 regulating network or simultaneous interactions of anions with the
      phospholipid-binding site and the R30 hydrogen bonding network triggered
      unfolding of the alpha2 C-end. An increase of anion density for two residues of
      the phospholipid-binding site (K1, R17, and Q22) or R17 and R19 and a preceding
      unfolding of the alpha2 C-end were necessary for unfolding of the alpha1 C-end.
      Anions interacted primarily with residues of the phospholipid-binding site and
      the R30 network while the alpha1/alpha2 hydrophobic region was void of anions.
      However, during strong interactions of anions with the R30 network and
      phospholipid-binding site, the alpha1/alpha2 hydrophobic region attracted anions
      which interacted with conserved residues of the alpha1 C-end. Analysis of anion
      induced rearrangements pointed to auxiliary residues of the R30 network and the
      phospholipid-binding site. Induction of conformational changes on the opposite
      ends of the alpha-helix core by interactions of anions with the phospholipid
      binding site may be relevant to a mechanism of membrane-permeabilizing activity.

PMID- 20060207
TI  - Diagnostic and therapeutic strategy for confounding radiation myelitis.
AB  - We report a case of confounding radiation myelitis to demonstrate the usefulness
      of surgical biopsy in ensuring the correct diagnosis and to avoid unnecessary
      treatment. The patient was a 40-year-old man with a history of epiglottis
      carcinoma and sarcoidosis. Six months after radiation therapy and chemotherapy
      for epiglottis carcinoma, he noticed paresthesia and dysesthesia in the left arm
      and leg. Two months after that, he complained of severe neck pain and rapidly
      progressing weakness in all extremities. MRI showed an enhanced intramedullary
      lesion with extensive edema in the cervical spinal cord. Radiation myelitis,
      intramedullary spinal tumor, and neurosarcoidosis were considered as differential
      diagnoses. Spinal cord biopsy with laminectomy was performed and radiation
      myelitis was diagnosed. After the surgery, the lesion was significantly decreased
      in size even though corticosteroid therapy was rapidly tapered. We emphasize that
      a spinal cord biopsy is indicated to obtain a pathological diagnosis and to make
      a clear treatment strategy for patients with associated diseases causing lesions
      of the spinal cord.

PMID- 20060208
TI  - Suberoylanilide hydroxamic acid limits migration and invasion of glioma cells in
      two and three dimensional culture.
AB  - High grade gliomas are aggressive cancers that are not well addressed by current
      chemotherapies, in large measure because these drugs do not curtail the diffuse
      invasion of glioma cells into brain tissue surrounding the tumor. Here, we
      investigate the effects of suberoylanilide hydroxamic acid (SAHA) on glioma cells
      in 2D and 3D in vitro assays, as SAHA has previously been shown to significantly
      increase apoptosis, decrease proliferation, and interfere with migration in other
      cell lines. We find that SAHA has significant independent effects on
      proliferation, migration, and invasion. These effects are seen in both 2D and 3D
      culture. In 3D culture, with glioma spheroids embedded in collagen I matrices,
      SAHA independently limits both glioma invasion and the reorganization of the
      tumor surroundings that usually proceeds such invasion. The decreased matrix
      reorganization and invasion is not accompanied by decreased production or
      activity of matrix-metalloproteases but instead may be related to increased cell
      cell adhesion.

PMID- 20060209
TI  - Photocatalytic activities for hydrogen evolution of new layered compound series
      HLaTa(x/3)Nb2-x/3O(7)/Pt (x=0, 2, 3, 4, and 6).
AB  - HLaTa(x/3)Nb(2-x/3)O(7) were synthesized by successive reactions of conventional
      solid-state reaction followed by ion exchange reaction. They were characterized
      by power X-ray diffraction, UV-vis diffusive reflectance and scan electron
      microscope. The effect of substitution of Ta for Nb in HLaNb(2)O(7) has been
      studied on the photocatalytic decomposition of water under UV light irradiation
      with methanol as electron donor and Pt as promoter catalyst. The x value in
      HLaTa(x/3)Nb(2-x/3)O(7) had an important effect on the photocatalytic activity of
      the catalyst. When x=2, HLaTa(2/3)Nb(4/3)O(7)/Pt shows a photocatalytic activity
      of 136 cm(3)g(-1)h(-1) hydrogen evolution in rate 10 vol.% methanol aqueous
      solution under irradiation with wavelength more than 290 nm from a 100-W mercury
      lamp.

PMID- 20060210
TI  - Combustion synthesis and effect of LaMnO3 and La0.8Sr0.2MnO3 on RDX thermal
      decomposition.
AB  - Perovskite-type LaMnO(3) and La(0.8)Sr(0.2)MnO(3) with high specific surface
      areas were prepared by stearic acid gel combustion method. The obtained powders
      were characterized by XRD, FT-IR, SEM and XPS techniques. Their catalytic
      activities were investigated on thermal decomposition of hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX) by TG-DSC techniques. The experimental results show that
      LaMnO(3) is a more effective catalyst than La(0.8)Sr(0.2)MnO(3) for the
      sublimation and melting process of RDX because of its higher concentration ratio
      of surface-adsorbed species. And the catalytic activity of La(0.8)Sr(0.2)MnO(3)
      is higher than that of LaMnO(3) for thermal decomposition of liquid RDX. This
      could be attributed to its higher concentration ratios of surface oxygen and
      Mn(4+)/Mn(3+). In conclusion, the concentration ratios of surface oxygen and
      Mn(4+)/Mn(3+) could play key roles for RDX thermal decomposition. This study
      points out a potential way to develop new and more active perovskite-type
      catalysts for the RDX thermal decomposition.

PMID- 20060211
TI  - Biosorption of copper(II) by immobilizing Saccharomyces cerevisiae on the surface
      of chitosan-coated magnetic nanoparticles from aqueous solution.
AB  - Immobilized Saccharomyces cerevisiae on the surface of chitosan-coated magnetic
      nanoparticles (SICCM) was applied as a new magnetic adsorbent for the adsorption
      of Cu(II) from aqueous solution. The prepared magnetic adsorbent was
      characterized by TEM, XRD and FTIR. TEM images indicated that S. cerevisiae was
      immobilized on the surface of chitosan-coated magnetic nanoparticles (CCM)
      successfully, and conglobation was not observed. The XRD pictures suggested that
      the Fe(3)O(4) nanoparticles were pure Fe(3)O(4) with a spinel structure and that
      the immobilizing process did not result in the phase change of Fe(3)O(4). Factors
      that influence the adsorption of Cu(II) were investigated, which included the
      initial pH of Cu(II) solution, initial concentration of Cu(II) solution and
      contact time. The optimum pH for Cu(II) absorption was 4.5. The highest removal
      efficiency of 96.8% was reached when the initial Cu(II) concentration was 60 mg
      L(-1), and the adsorption capacity was increased with the increase of initial
      concentration of Cu(II). In particular, SICCM was highly efficient for the fast
      adsorption of Cu(II) within the first 10 min, and adsorption equilibrium could be
      achieved in 1h. Equilibrium studies show that the data of Cu(II) adsorption
      follow the Langmuir model. The maximum adsorption capacity for Cu(II) was
      estimated to be 144.9 mg g(-1) with a Langmuir adsorption equilibrium constant of
      0.0719 L mg(-1) at 301 K.

PMID- 20060212
TI  - Aquatic worms eat sludge: mass balances and processing of worm faeces.
AB  - Reduction of the amount of waste sludge from waste water treatment plants (WWTPs)
      can be achieved with the aquatic worm Lumbriculus variegatus in a new reactor
      concept. In addition to reducing the amount of waste sludge, further processing
      of produced worm faeces and released nutrients should also be considered. This
      study gives the mass balances for sludge consumed by L. variegatus, showing the
      fate of the consumed organic material, nutrients and heavy metals associated with
      the sludge. A distinction is made between conversion into worm biomass, release
      as dissolved metabolites and what remains in the worm faeces. The results showed
      that 39% of the nitrogen and 12% of the phosphorus in the sludge digested by the
      worms are used in the formation of new worm biomass, which has potential for
      reuse. Experiments showed that settling of the worm faeces leads to a factor 2.5
      higher solids concentration, compared to settling of waste sludge. This could
      lead to a 67% reduction of the volumetric load on thickening equipment. The worm
      reactor is expected to be most interesting for smaller WWTPs where a decrease on
      the volumetric load on sludge handling operations will have most impact.

PMID- 20060213
TI  - Stabilization/solidification of an alkyd paint waste by carbonation of waste-lime
      based formulations.
AB  - The application of solvent-based paints by spraying in paint booths is
      extensively used in a wide range of industrial activities for the surface
      treatment of a vast array of products. The wastes generated as overspray
      represent an important environmental and managerial problem mainly due to the
      hazardous characteristics of the organic solvent, rendering it necessary to
      appropriately manage this waste. In this paper a solidification/stabilization
      (S/S) process based on accelerated carbonation was investigated as an
      immobilization pre-treatment prior to the disposal, via landfill, of an alkyd
      solvent-based paint waste coming from the automotive industry; the purpose of
      this S/S process was to immobilize the contaminants and reduce their release into
      the environment. Different formulations of paint waste with lime, lime-coal fly
      ash and lime-Portland cement were carbonated to study the effect of the
      water/solid ratio and carbonation time on the characteristics of the final
      product. To assess the efficiency of the studied S/S process, metals, anions and
      dissolved organic carbon (DOC) were analyzed in the leachates obtained from a
      battery of compliance and characterization leaching tests. Regarding the
      carbonation of paint waste-lime formulations, a mathematical expression has been
      proposed to predict the results of the leachability of DOC from carbonated
      mixtures working at water/solid ratios from 0.2 to 0.6. However, lower DOC
      concentrations in leachates (400mg/kg DOC in L/S=10 batch leaching test) were
      obtained when carbonation of paint waste-lime-fly-ash mixtures was used at 10h
      carbonation and water to solid ratio of 0.2. The flammability characteristics,
      the total contents of contaminants and the contaminant release rate in compliance
      leaching tests provide evidence for a final product suitable for deposition in
      non-hazardous landfills. The characterization of this carbonated sample using a
      dynamic column leaching test shows a high stabilization of metals, partial
      immobilization of Cl(-), SO(4)(2-), F(-) and limited retention of DOC. However,
      the obtained results improve the previous findings obtained after the paint waste
      S/S using uncarbonated formulations and would be a useful pre-treatment technique
      of the alkyd paint waste prior to its disposal in a landfill.

PMID- 20060214
TI  - Study on removal of cadmium by hybrid liquid membrane process.
AB  - Removal of cadmium as a hazardous heavy metal is studied by applying a new design
      of hybrid cell for liquid membrane process. Tri-iso-octyl amine (TIOA) is used as
      the carrier in the organic phase. The concentration of cadmium in the samples is
      measured by atomic absorption spectroscopy. The effect of various parameters
      including type of supporting membrane, pH of feed and stripping phases, initial
      concentration of cadmium, carrier concentration, solvent nature, and also organic
      film resistance on mass transfer rate and removal efficiency are studied. The
      effect of temperature on mass transfer flux is studied by proposing a prediction
      model. The optimum carrier concentration is found to be about 0.05 M. The
      appropriate values of pH for feed and stripping phases are about 3 and 13,
      respectively.

PMID- 20060215
TI  - Adsorption of Remazol Black 5 from aqueous solution by the templated crosslinked
      chitosans.
AB  - The templated crosslinked-chitosan microparticles prepared using the imprinting
      method with the Remazol Black5 (RB5) dye as a template, epichlorohydrin (ECH) as
      a crosslinker, and sodium hydroxide (NaOH) solution used for the microparticle
      formation showed the highest adsorption capacity for the RB5 dye compared with
      those that used other methods with or without a template, three crosslinkers, and
      two microparticle formations. The results showed that the adsorption of the RB5
      dye on the microparticles was affected by the microparticle size, the initial dye
      concentration, the initial pH value, as well as the temperature. Both kinetics
      and thermodynamic parameters of the adsorption process were estimated. These data
      indicated an exothermic spontaneous adsorption process that kinetically followed
      the second-order adsorption process. Equilibrium experiments fitted well the
      Langmuir isotherm model, and the maximum monolayer adsorption capacity for the
      RB5 dye was 2941 mg/g. The competition study showed that the adsorption of the
      RB5 dye on the microparticles in the mixture solution was much less affected by
      the existence of the 3R dye than the other way around. Furthermore, the
      microparticles could be regenerated through the desorption of the dye in pH 10.0
      of NaOH solution and could be reused to adsorb the dye again.

PMID- 20060216
TI  - Pyrohydrolytic determination of fluorine in coal: a chemometric approach.
AB  - Corrosion effects in thermal power plants and environmental impact cause an
      increase in demand for fluorine analysis in coal. Solid sample decomposition,
      organic and inorganic fluorine compounds, volatility of fluorine species are
      problems which deserve a special attention. The aim of this work was to optimize
      the pyrohydrolytic (Phy) determination of fluorine content in the lignite coal.
      The parameters of pyrohydrolysis were evaluated and optimized by two statistical
      methods: Plackett-Burman (PB) design and response surface methodology (RSM). The
      content of fluorine in the absorption solution was measured by fluoride ion
      selective electrode. The limit of detection of the proposed method was 20 microg
      g(-1), with good recovery (95%) and relative standard deviation less than 5%.
      With such benefits as simplicity, precision, accuracy and economy, this method is
      highly suitable for routine analysis of coal.

PMID- 20060217
TI  - Influence of calcination on the adsorptive removal of phosphate by Zn-Al layered
      double hydroxides from excess sludge liquor.
AB  - The influence of calcination of Zn-Al layered double hydroxides (LDHs) on their
      phosphate adsorption capacity was studied in order to improve phosphorus removal
      from an excess sludge liquor. Powder X-ray diffraction (XRD), Fourier transform
      infrared (FTIR) spectroscopy, scanning electron microscopy (SEM),
      thermogravimetry-differential scanning calorimetry (TG-DSC) and nitrogen
      adsorption-desorption were employed to characterize the raw Zn-Al and the
      calcined products. The results reveal that the Zn-Al LDHs evolved to a phase of
      mixed metal oxides with the calcination temperature increasing to 300 degrees C
      and finally to spinel ZnAl(2)O(4) at 600 degrees C. When the Zn-Al was calcined
      at 300 degrees C, the interlayer carbonate ions were removed and the greatest BET
      surface area of 81.20 m(2)/g was achieved. The tested phosphate adsorption
      capacities of the raw and calcined Zn-Al were closely related to the evolution of
      physicochemical properties of the LDHs during the calcination. The Zn-Al-300 (Zn
      Al LDHs calcined at 300 degrees C) exhibited the highest P uptake of 41.26 mg P/g
      in 24h. The phosphate adsorption by the raw Zn-Al and the Zn-Al-300 both follows
      a pseudo-second-order kinetic model; the adsorption isotherms show a good fit
      with a Langmuir-type equation.

PMID- 20060218
TI  - Interaction of debris with a solid obstacle: numerical analysis.
AB  - The subject of this research is the propagation of a cloud of solid particles
      formed from an explosion-damaged construction. The main objective is the
      interaction of the cloud (debris) with a solid beam located at some distance from
      the explosion. The mathematical model involves the flow of the gas using standard
      conservation equations, and this part of the model is solved numerically. The
      solid particles are treated as a system of solid points (so-called Lagrangian
      approach), whose motion is the result of the flowing gas as well as collisions
      with obstacles. These two issues are described respectively by Newton's second
      law and the hard-sphere model. The model is used to simulate various cases where
      the influence of different parameters like the value of the pressure of the
      explosion, the particle size, the number of particles and the obstacle location
      are investigated. The results are presented as snapshots of particle location,
      and also as the particle total momentum during collision with the beam.

PMID- 20060219
TI  - Cadmium in animal production and its potential hazard on Beijing and Fuxin
      farmlands.
AB  - A random sample of pairs of animal feeds and manures were collected from 215
      animal barns in Beijing and Fuxin regions of China. The concentrations of Cd in
      manures and feeds ranged from non-detectable to 129.8 mg/kg dry weight and non
      detectable to 31 mg/kg dry weight, respectively. The concentrations of Cd in pig,
      dairy cow and chicken manures were positively correlated to those in their feeds.
      About 30% of the manure samples contained Cd concentrations higher than the upper
      limit for use in farmlands, and pig and chicken manures might be the primary
      contributors of Cd to farmlands. The farmlands in Beijing and around the Fuxin
      Downtown areas would exceed the soil quality criteria within several decades
      according to current manure Cd loading rates. Undoubtedly, more scientific animal
      production and manure management practices to minimize soil pollution risks are
      necessary for the two regions.

PMID- 20060220
TI  - Enrichment of chlorobenzene and o-nitrochlorobenzene on biomimetic adsorbent
      prepared by poly-3-hydroxybutyrate (PHB).
AB  - Poly-3-hydroxybutyrate (PHB) was used as a new material to prepare a biomimetic
      adsorbent by a modified double emulsion solvent evaporation technique. The
      enrichment capacities of the adsorbent for the toxic liposoluble organic
      compounds were evaluated by chlorobenzene (CB) and o-nitrochlorobenzene (o-NCB)
      with the adsorption isotherms, enrichment factor (EF) and enrichment kinetics.
      The results showed that Sips isotherm fitted the experimental data better than
      Langmuir and Freundlich models, as well as the pseudo-second order kinetic model
      fitted better than the first order model. For CB and o-NCB, the maximum
      adsorption capacity was 125.99 and 39.56 m gg(-1), while the maximum EF was 1204
      and 1149 at 20 degrees C for 36h, though the specific surface area (BET) of the
      adsorbent was only 8.45 m(2)g(-1). CB had a higher EF than o-NCB because the
      hydrophilic group (-NO(2)) decreases the liposoluble ability of o-NCB. K(ow) has
      a positive correlation with EF, so the organochlorine compounds are liable to be
      adsorbed by the adsorbent. The results indicated that PHB, even
      polyhydroxyalkanoates, can be a new biodegradable adsorption material.

PMID- 20060221
TI  - Manganese removal from aqueous solution using a thermally decomposed leaf.
AB  - As a significant agricultural and industrial raw material, Mn(II) has been
      intensively used and widely distributed in the environment. Recent studies
      indicate that Mn(II) could cause acute toxicity to aqueous livings and human
      beings. The treatment of Mn(II) contained wastewater is stringent for
      environmental preservations. This paper attempts to testify the performance of
      Mn(II) adsorption by a novel adsorbent, natural leaf that was partially
      decomposed at moderate temperature. The isothermal adsorption shows high
      prevalence for Mn(II) with adsorption capacity determined at 61-66 mg g(-1).
      Various factors including adsorbent dosage, pH, temperature and equilibration
      time were investigated regarding the effects on Mn(II) adsorption. It was shown
      that a rapid equilibration within 30 min could be achieved at pH values as low as
      4.0 while an endothermic and spontaneous process could be disclosed with enthalpy
      change ranged from 13 to 0.78 kJ mol(-1) and the entropy change ranged from 
      35.79 to -11.58 kJ mol(-1) from 5 to 55 degrees C, separately. Spectroscopy study
      revealed chemisorptions relevant to phosphate, ferrous oxide and carbonate
      groups, and a physisorption on carbon black, which were main components of the
      adsorbent. No obvious linkage was observed between Mn(II) adsorption and the
      amine group which is critical to heavy metal adsorption in previous studies. The
      proposed preparation method and the basic guidelines regarding the adsorbents'
      selection seem promising in the engineering practices.

PMID- 20060222
TI  - Toxicity evaluation and prediction of toxic chemicals on activated sludge system.
AB  - The gaps of data for evaluating toxicity of new or overloaded organic chemicals
      on activated sludge system resulted in the requirements for methodology of
      toxicity estimation. In this study, 24 aromatic chemicals typically existed in
      the industrial wastewater were selected and classified into three groups of
      benzenes, phenols and anilines. Their toxicity on activated sludge was then
      investigated. Two indexes of IC(50-M) and IC(50-S) were determined respectively
      from the respiration rates of activated sludge with different toxicant
      concentration at mid-term (24h) and short-term (30min) time intervals.
      Experimental results showed that the group of benzenes was the most toxic,
      followed by the groups of phenols and anilines. The values of IC(50-M) of the
      tested chemicals were higher than those of IC(50-S). In addition, quantitative
      structure-activity relationships (QSARs) models developed from IC(50-M) were more
      stable and accurate than those of IC(50-S). The multiple linear models based on
      molecular descriptors and K(ow) presented better reliability than single linear
      models based on K(ow). Among these molecular descriptors, E(lumo) was the most
      important impact factor for evaluation of mid-term toxicity.

PMID- 20060223
TI  - "Evaluation of small-scale constructed wetland for water quality and Hg
      transformation. ' by P. Chavan et al.

PMID- 20060224
TI  - Leaching zinc from spent catalyst: process optimization using response surface
      methodology.
AB  - The spent catalyst from vinyl acetate synthesis contains large quantity of zinc.
      The present study attempts to leach zinc using a mixture of ammonia, ammonium
      carbonate and water solution, after microwave treatment. The effect of important
      parameters such as leaching time, liquid/solid ratio and the ammonia
      concentration was investigated and the process conditions were optimized using
      surface response methodology (RSM) based on central composite design (CCD). The
      optimum condition for leaching of zinc from spent catalyst was identified to be a
      leaching time of 2.50 h, a liquid/solid ratio of 6 and ammonia concentration 5.37
      mol/L. A maximum of 97% of zinc was recovered under the optimum experimental
      conditions. The proposed model equation using RSM has shown good agreement with
      the experimental data, with a correlation coefficient (R(2)) of 0.95. The samples
      were characterized before and after leaching using X-ray diffraction (XRD),
      nitrogen adsorption and scanning electron microscope (SEM).

PMID- 20060225
TI  - Partial degradation mechanisms of malachite green and methyl violet B by
      Shewanella decolorationis NTOU1 under anaerobic conditions.
AB  - This work demonstrated that Shewanella decolorationis NTOU1 decolorized 200 mg l(
      1) of crystal violet, malachite green, or methyl violet B within 2-11h under
      anaerobic conditions at 35 degrees C. The initial color removal rate of malachite
      green was highest, while that of methyl violet was lowest. GC/MS analyses of the
      intermediate compounds produced during and after decolorization of malachite
      green and methyl violet B suggested that biodegradation of these dyes involved
      reduction to leuco form, N-demethylation, and reductive splitting of the
      triphenyl rings. The number of N-methylated groups of these dyes might have
      influenced decolorization rates and the reductive splitting of the triphenyl
      rings of these dyes. Cytotoxicity and antimicrobial test data showed that
      malachite green and methyl violet B solution (100 mg l(-1)) were toxic. Toxicity
      of the dyes decreased after their decolorization, but further incubation resulted
      in increased toxicity.

PMID- 20060226
TI  - Women's preferences for masculinity in male faces are highest during reproductive
      age range and lower around puberty and post-menopause.
AB  - Masculinity in male faces is thought to be a sign of mate quality and is
      associated with measures of long-term health. Previous studies have demonstrated
      that women's masculinity preferences change across the menstrual cycle with women
      preferring more masculine men during phases of the menstrual cycle where
      fertility is highest (i.e. the late follicular phase). Given the hormonal
      correlates of such preferences and that these hormones change across the life
      span, we tested for differences in female masculinity preferences at different
      ages. We compared the masculinity preferences of peri-pubescent girls and young
      adult women (Study 1), circum-menopausal women reporting to either be pre- or
      post-menopause (Study 2), and a large sample of women across a wide range of ages
      (Study 3). In all three studies, preferences for masculinity in male faces were
      highest in women who were at a reproductively active age. Preferences for
      masculinity were lower when females were peri-pubescent, post-menopausal, or at
      ages corresponding to these groups. These data support the notion that
      masculinity in male faces is an important trait for reproductively relevant mate
      choice decisions. These data also highlight a shift in female visual preferences
      for men that is associated with important stages of the lifespan. Visual
      preferences appear to track important hormonal changes associated with age; as
      women pass puberty their preferences shift towards facial traits associated with
      mate quality and as women undergo menopause their preferences for such facial
      traits decrease. Overall, these results demonstrate the important role of
      reproductive status and support the notion that preferences for male faces are
      tied to reproductively relevant hormones.

PMID- 20060227
TI  - Validation of the Drinking Context Scale (DCS-9) for use with non-adjudicated
      first-year college students.
AB  - The Drinking Context Scale (DCS-9) has been used to measure the impact of
      drinking during social, emotional, and situational contexts. Psychometric
      properties remain unevaluated in a population of non-adjudicated first-year
      college students in the southeast. Liseral 8.8 was used to test the factorial
      validity of the DCS, using Confirmatory Factor Analysis. The original three
      factor model for the DCS represented acceptable fit to the data (chi(2)=36.72,
      df=24, p=0.047, CFI=0.991, SRMR=.0406) supporting its use with first-year college
      students. Invariance between gender, ethnic group, and geographical regions
      should be examined by future researchers.

PMID- 20060228
TI  - Cognitive-affective characteristics of smokers with and without posttraumatic
      stress disorder and panic psychopathology.
AB  - The present study evaluated differences among daily smokers with posttraumatic
      stress disorder (PTSD), panic disorder (PD), panic attacks (PA), and no axis I
      psychopathology (past 6 months) in terms of several cognitive-affective variables
      implicated in both the onset and maintenance of anxiety psychopathology and
      cigarette smoking. The sample consisted of 123 daily smokers (62% women:
      M(age)=29.7, SD=11.9). Compared to the PA and no psychopathology groups, the PTSD
      group reported significantly higher levels of anxiety sensitivity, discomfort
      intolerance, negative affectivity, anxious arousal, and anhedonic depression;
      and, the PTSD group reported significantly lower levels of perceived control over
      anxiety-related events than the PA group. The PD group, compared to those in the
      PA and no psychopathology groups, reported significantly higher levels of anxiety
      sensitivity, negative affectivity, and anxious arousal; and significantly lower
      levels of perceived control over anxiety-related events. No significant
      differences were evident between the PTSD and PD groups. Theoretical and clinical
      implications of the present findings are discussed in terms of smoking and
      emotional vulnerability.

PMID- 20060229
TI  - A pilot study of mailed nicotine lozenges with assisted self-help for the
      treatment of smokeless tobacco users.
AB  - Smokeless tobacco (ST) is associated with adverse health consequences yet
      treatment resources for ST are not widely available. Cost-effective behavioral
      interventions incorporating self-help materials and counseling calls have been
      demonstrated to reduce ST use rates and can be easily disseminated, but the
      feasibility and effectiveness of incorporating pharmacotherapy into this approach
      have not been evaluated. We conducted a clinical pilot study randomizing 60
      patients to 12 weeks of the 4-mg nicotine lozenge or placebo delivered through
      the mail. All subjects received an assisted self-help intervention (ASH) with
      telephone support. At the end of the medication phase, lozenges were being used
      by 63% of subjects in the 4-mg nicotine lozenge group and 43% in placebo. The
      nicotine lozenge decreased composite withdrawal symptoms and adverse events were
      minimal. No significant differences were observed in abstinence rates between the
      two groups at 3 or 6 months. We conclude that the mailing of nicotine lozenges to
      ST users is a feasible and safe strategy the efficacy of which needs to be
      evaluated.

PMID- 20060230
TI  - Influenza caused epidemic encephalitis (encephalitis lethargica): the
      circumstantial evidence and a challenge to the nonbelievers.
AB  - Twenty years ago, circumstantial evidence was compiled to link the 1918 pandemic
      influenza virus to a CNS disorder called epidemic encephalitis or encephalitis
      lethargica. A challenge was issued to naysayers. During the past two decades, the
      knowledge about the influenza virus and the 1918 pandemic virus in particular has
      had dramatic advancement. The 1918 virus has been resurrected and reconstructed.
      Experimental studies of mice inoculated with a neurovirulent avian virus have
      delineated the neuropathology of influenza encephalitis. Review of autopsy cases
      of encephalitis lethargica revealed that the neuropathology during and shortly
      after the pandemic was unique. Surprisingly two different viruses were involved
      with the great pandemic. A single amino acid difference in the hemagglutinin of
      the two viruses changed the preferred receptor of the virus in the host cell. One
      virus has qualities that suggest that it is neurovirulent. Circumstantial
      evidence suggests that the cause of death in some influenza patients was
      neurogenic congestive heart failure with pulmonary edema. Theories about the
      pathophysiology of encephalitis lethargica and postencephalitic Parkinson's
      disease are offered.

PMID- 20060231
TI  - Intrinsic hand muscle reinnervation by median-ulnar end-to-side bridge nerve
      graft: case report.
AB  - Recovery of either the motor or sensory functions has not been consistently
      achieved in upper extremity end-to-side neurorrhaphy; this technique was only
      indicated when more conventional nerve repair was not possible. In most studies,
      the whole median or ulnar nerve was used for end-to-side neurotization. In this
      report, we present 4 cases of high-median or ulnar nerve laceration in which a
      nerve graft was placed end-to-side between the median and ulnar motor fascicles
      close to the wrist. At 4 months after surgery, 3 of 4 patients began to recover
      active movement of the affected small muscles of the hand. EMG and nerve
      conduction studies confirmed that nerve conduction was through the nerve grafts.

PMID- 20060232
TI  - A radiocarpal ligament reconstruction using brachioradialis for secondary ulnar
      translation of the carpus following radiocarpal dislocation: a cadaver study.
AB  - PURPOSE: Radiocarpal dislocation damages the radiocarpal ligaments, typically
      eliminating the possibility for repair. The goals of this study were to create a
      model for ulnar translation of the carpus and design a soft-tissue reconstruction
      using the brachioradialis (BR) to prevent ulnar translation of the carpus. We
      primarily sought to recreate the stabilizing effect of the radioscaphocapitate
      ligament. METHODS: Eight cadaveric upper limbs were dissected, leaving only the
      BR tendon. The wrist was loaded perpendicular to the long axis of the forearm,
      and load-displacement curves for ulnar translation were generated. The
      radiocarpal ligaments were sectioned. Substantial ulnar translation was seen only
      after complete release of the palmar and dorsal radiocarpal ligaments.
      Reconstruction was performed with the BR tendon, maintaining the insertion on the
      radial styloid. The proximal tendon stump was brought distally through a drill
      hole in the center of the capitate, palmar to dorsal, and secured to the dorsal
      rim of the radius with a suture anchor. The specimens were then retested after
      this reconstruction. Qualitative evaluation of graphs plotted, mini c-arm
      fluoroscopy, and visual observation was also performed. RESULTS: Comparison of
      the intact specimens and the specimens after sectioning of the radiocarpal
      ligaments revealed a significant difference between mean ulnar translation (11.1
      mm vs 18.4 mm; p < 0.05). Comparison of the sectioned specimens before and after
      BR reconstruction demonstrated a statistically significant difference in mean
      ulnar translation (18.4 mm vs 10.6 mm; p < 0.05). Comparison of the intact
      specimens and the specimens after sectioning-reconstruction did not demonstrate a
      significant difference, indicating that the BR reconstruction re-established the
      stability seen in the intact specimens with regard to ulnar translation (11.1 mm
      vs 10.6 mm; p > 0.05). CONCLUSIONS: The model consistently produced significant
      ulnar translation after division of the radiocarpal ligaments. The BR
      reconstruction was primarily designed to restore the function of the
      radioscaphocapitate ligament. This biomechanical study demonstrates the ability
      of this reconstruction to generate a statistically significant restraint to ulnar
      translation in a cadaver model of radiocarpal dislocation.

PMID- 20060233
TI  - Differential strain of the axially loaded scapholunate interosseus ligament.
AB  - PURPOSE: To directly measure strain changes in the scapholunate ligament via
      magnetic resonance imaging (MRI) when axially loading the wrist in the neutral
      and extended positions. METHODS: Six asymptomatic male volunteers without known
      history of previous wrist injury were enrolled in this MRI-based study. Each
      subject underwent 3 MRI scans in a 3T scanner: in resting neutral position, in
      neutral with axial load applied, and in extension with axial load applied. Axial
      load was applied via extension of an elastic band with known force/elongation
      curve. We analyzed images and converted them to 3-dimensional stereolithographs.
      Attachment points of the palmar, proximal, and dorsal sections of the
      scapholunate interosseus ligament (SLIL) were identified. The lengths of the
      resulting vectors were recorded for each position. Strain, defined as change in
      length divided by original length, was calculated for the axially loaded neutral
      and extended wrists. We used the Bonferroni adjusted multiple comparisons from an
      analysis of variance model, with statistical significance defined as p < .05.
      RESULTS: Strains were significantly greater in the palmar (p = .02) and proximal
      (p = .01) subregions of the SLIL in loaded extension versus loaded neutral
      positions. In contrast, the strain on the dorsal component in extension was not
      statistically greater than in the neutral position (p = .45). Axial load in
      neutral resulted in minimal strain of all 3 components of the SLIL complex, and
      these were not significantly different from each other (p > .99). With extension,
      the strains of the palmar (p = .03) and proximal (p = .006) regions were
      statistically greater than that of the dorsal component. CONCLUSIONS: In
      extension, strain is greatest in the palmar and proximal portions of the intact
      SLIL. Axial load in neutral applies minimal strain to the SLIL complex. Avoiding
      axial loading in extension and encouraging loading in neutral position may allow
      for decreased injury and more effective healing of the scapholunate ligament.

PMID- 20060234
TI  - Role of low-affinity nerve growth factor receptor inhibitory antibody in reducing
      pain behavior and calcitonin gene-related Peptide expression in a rat model of
      wrist joint inflammatory pain.
AB  - PURPOSE: Nerve growth factor (NGF), via the high-affinity receptor, tyrosine
      kinase A, has been widely reported as a mediator of pain caused by inflammation.
      A clinical trial has suggested that anti-NGF antibody is effective for pain
      caused by osteoarthritis of the knee. However, adverse events such as headache
      (8.9%), upper respiratory tract infection (7.3%), and paresthesia (6.8%) were
      reported. We hypothesized that inhibition of the low-affinity NGF receptor, p75
      neurotrophin receptor (p75NTR), is also effective for joint pain and may reduce
      side effects. This study examined suppression of pain behavior and expression of
      pain-inducing neuropeptides such as calcitonin gene-related peptide (CGRP) and
      p75NTR in dorsal root ganglia neurons by a p75NTR inhibitory antibody in a rat
      model of wrist joint inflammatory pain. METHODS: We injected complete Freund's
      adjuvant (CFA) into the wrist joint of rats and used this as a model of
      inflammatory pain. We applied 10 microL of saline (CFA + saline group; n = 20) or
      1, 10, or 50 microL of a p75NTR inhibitory antibody (CFA + p75NTR inhibitory
      antibody group; n = 40) directly to the inflamed joint in the rats. Mechanical
      hyperalgesia was measured for 2 weeks using von Frey filaments. We assessed CGRP
      and p75NTR expression in C8 dorsal root ganglia immunochemically. Adverse events
      such as loss of weight and/or appetite, constipation, and infection were
      examined. RESULTS: p75NTR inhibitory antibody reduced mechanical hyperalgesia
      caused by CFA (p<.05 vs controls) in the rat model (p<.01 vs saline), without any
      adverse events. We found that 10 and 50 microL of a p75NTR inhibitory antibody
      were more effective for pain, without a significant difference between doses.
      CGRP and p75NTR immunoreactivity was upregulated in the CFA + saline groups
      compared with a control group (p<.01). However, direct p75NTR inhibitory antibody
      application decreased CGRP and p75NTR expression after wrist inflammation
      (p<.01). CONCLUSIONS: p75NTR inhibition may be a therapeutic target for inflamed
      joint pain treatment with reduced adverse events.

PMID- 20060235
TI  - Subungual extraskeletal chondroma with finger nail deformity: case report.
AB  - We report a subungual extraskeletal chondroma with a convex nail deformity
      originating from the index finger in a 39-year-old man. The tumor was excised and
      its histopathology showed obvious nuclear pleomorphism. However, the Ki-67 (MIB
      1) labeling index was less than 1%, indicating low proliferative activity; it was
      classified as an extraskeletal chondroma with atypical features. There was no
      recurrence over a 3-year postoperative period.

PMID- 20060236
TI  - Five-year follow-up of carpal tunnel release in patients over age 65.
AB  - PURPOSE: In 2005, a prospective clinical trial with a 6-month follow-up
      demonstrated the efficacy of carpal tunnel release in patients 65 years and older
      and showed that age is not a contraindication to surgery. The purpose of this
      study was to determine whether there was any further improvement, maintenance of
      results, or recurrence of carpal tunnel symptoms 5 years after surgery. METHODS:
      We contacted all 66 patients (with a total of 92 hands involved) from the
      original study to be enrolled for re-evaluation. Of the original cohort, 12 were
      unavailable because of death or severe neurologic impairment. Of the remaining 54
      patients, 19 agreed to participate in this follow-up study of their 29 hands. For
      the 5-year follow-up, patients underwent a repeat history and physical
      examination with particular emphasis on the status of their hands over the past 5
      years. The Michigan Hand Outcome Questionnaire was again used to determine
      overall hand function, activities of daily living, work performance, pain,
      aesthetics, and satisfaction with hand function. RESULTS: The mean age of
      patients available for 5-year follow-up was 78 +/- 3 years. The patients
      maintained their symptom improvement, demonstrating no significant difference
      between the 6-month and 5-year follow-up data; their physical findings, except
      for grip strength, were likewise unchanged. The patients also retained their
      improved 2-point discrimination. Scar tenderness decreased over the 5 years. The
      Michigan Hand Outcome Questionnaire confirmed the fact that initial postoperative
      improvement in all parameters persisted at least 5 years. One patient underwent
      repeat carpal tunnel release of 1 hand for recurrent symptoms. Overall, 94% of
      patients were either very or completely satisfied with their results.
      CONCLUSIONS: Patients who were 65 years of age or older at the time of surgery
      maintained their clinical improvement for at least 5 years after surgery. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 20060237
TI  - Relationship of combat experiences to alcohol misuse among U.S. soldiers
      returning from the Iraq war.
AB  - OBJECTIVE: Studies have shown a relationship between combat experiences and
      alcohol misuse in military personnel; it is not known if there are specific
      combat experiences that confer a greater risk. The current study examined the
      association of specific types of combat experiences with a positive screen for
      alcohol misuse. METHODS: 1120 U.S. soldiers who were members of brigade combat
      infantry teams were surveyed anonymously 3-4 months after returning from
      deployment to Iraq regarding their experiences in combat and their physical and
      mental health. Combat items were independently rated and placed into the
      following categories: (1) Fighting; (2) Killing; (3) Threat to oneself; (4)
      Death/injury of others; (5) Atrocities; and, (6) Positive experiences. Alcohol
      misuse was measured using a 2-item alcohol screen combined with alcohol-related
      behavioral items. RESULTS: Of the soldiers sampled, 25% (N=275) screened positive
      for alcohol misuse 3-4 months post-deployment; 12% (N=125) screened positive and
      exhibited alcohol-related behavioral problems. Most combat exposure factors were
      significantly related to alcohol misuse individually. When factors were analyzed
      simultaneously, soldiers who had higher rates of exposure to the threat of
      death/injury were significantly more likely to screen positive for alcohol
      misuse; exposure to atrocities predicted misuse of alcohol with alcohol-related
      behavioral problems. CONCLUSIONS: High exposure to threatening situations and
      atrocities was associated with a positive screen for alcohol misuse. Clinicians
      treating combat veterans should be aware of the potential association of alcohol
      misuse with specific types of experiences and closely follow those soldiers upon
      their return home.

PMID- 20060238
TI  - Estimation of the number of injection drug users in St. Petersburg, Russia.
AB  - The conjoined epidemics of HIV and injection drug abuse have progressed rapidly
      in many parts of the Russian Federation, including the City of St. Petersburg,
      which now has more cases of HIV than any other region in the country. Official
      estimates of the number of injection drug users (IDUs), which rely on official
      registration of IDUs, greatly underestimate their number. We have combined
      official statistics that register HIV cases and attribute risk to causes
      including injection drug use with data from a study that collected data from IDUs
      about their HIV serostatus and their history of HIV testing to estimate the
      number of IDUs in the city. We conclude that there are 83,118+/-5799 total IDUs.
      Since many IDUs have not been tested and even some who have been officially
      tested do not know their serostatus, a first step in countering the growing HIV
      epidemic among IDUs in St. Petersburg must be expanded access to HIV testing,
      prevention, and treatment that is targeted to IDUs.

PMID- 20060239
TI  - Effects of risk perception of marijuana use on marijuana use and intentions to
      use among adolescents in Bogota, Colombia.
AB  - BACKGROUND: Perceived risk is a key concept of behavioral theories used to
      predict substance use among youth and a core component of drug use prevention
      interventions. The present study aimed to (1) assess degrees of risk perception
      of regular marijuana use, (2) identify factors associated with risk perception,
      and (3) explore the associations between perceived risk and marijuana use and
      intentions to use marijuana among school-attending adolescents in Bogota,
      Colombia. METHODS: Data from 2079 standardized questionnaires administered in 23
      schools were analyzed in this study. Schools were selected in a multi-stage
      probability cluster sample to reflect the socio-economic characteristics of
      Bogota's student population. RESULTS: Just over 11% of participants perceived
      regular marijuana use to be a low risk behavior. Older age (>16 years) (adjusted
      odds ratio=2.9; 95% confidence interval=1.4-6.0) and low level of knowledge
      regarding the physical and psychological harms of illegal drugs (AOR=2.9;
      95%CI=2.0-4.3) were the strongest predictors of low risk perception, Low
      perceived risk was also significantly associated with ever having used marijuana
      (AOR=2.5; 95%CI=1.7-3.7), monthly marijuana use among ever marijuana users
      (AOR=2.7; 95%CI=1.4-5.0), and a positive intention to use marijuana within the
      next 12 months among non-users (AOR=2.1; 95%CI=1.4-3.5). CONCLUSIONS: Consistent
      with previous findings, perceiving regular marijuana use as a risky behavior
      functions as a protective factor against the intention to use, use and occasional
      use of marijuana. Incorporation of this message into drug use prevention
      activities for non-users and early-stage users may enhance their effectiveness.

PMID- 20060240
TI  - Melatonin secretion during postnatal development in wild and domestic female
      lambs.
AB  - This study examines the patterns of melatonin secretion during postnatal
      development in wild (mouflon; n = 7) and domestic (Spanish Merino; n = 6) female
      lambs under their natural photoperiod conditions. The aim was to determine
      whether these types of sheep which differ in the timing of puberty, also differ
      in the establishment of daily melatonin secretory rhythms and/or in the nocturnal
      plasma melatonin secretion. In addition, the time when the lambs first reached
      nocturnal levels of melatonin similar to adults was also evaluated. For this
      purpose, the melatonin secretion in lambs was compared with those of their
      mothers. A day/night (D/N) difference in plasma melatonin concentration was
      noticed as early as 1 day after birth in the Merino female lambs (D: 5.9 +/- 1.0
      pg/ml compared to N: 22.0 +/- 3.3 pg/ml; p < 0.05), and by 1 week after birth in
      the mouflon female lambs (D: 4.9 +/- 0.3 pg/ml compared to N: 56.9 +/- 15.3
      pg/ml; p < 0.05). An effect of the genotype (p < 0.05) and age (p < 0.01) was
      detected on mean nocturnal plasma melatonin concentrations, which were lower in
      the Merino than in the mouflon lambs. Night-time plasma concentration of
      melatonin was also high in mouflon than in Merino mothers (p < 0.05). No
      differences were detected between the wild genotype and the domestic one in the
      time when the lambs first reached nocturnal levels of melatonin similar to those
      of their mothers.

PMID- 20060241
TI  - Imaging and biomarkers for Alzheimer's disease.
AB  - The development of acetyl-cholinesterase inhibitors, and the prospect of future
      therapies to prevent, or modify, the course of Alzheimer's disease necessitates
      greater accuracy in diagnosis of this heterogeneous disease. Current diagnosis is
      based on clinical criteria and neuropathology. This is not always sufficient, and
      the development of sensitive and specific biomarkers would enable earlier and
      more accurate diagnosis. Genetic markers, such as Apolipoprotein E4, and
      cerebrospinal fluid markers such as beta-amyloid and tau, support a diagnosis of
      Alzheimer's disease. The latter can also predict conversion from mild cognitive
      impairment to dementia. Imaging markers improve diagnostic accuracy by reflecting
      brain function or aspects of in vivo pathological changes. In order for such
      biomarkers to become clinically useful, however, effective treatments need to
      become available, and long-term follow-up studies are necessary to evaluate the
      relevance of cross-sectional biomarker changes for the longitudinal natural
      history of the disease.

PMID- 20060242
TI  - Rapid and simple determination of psychotropic phenylalkylamine derivatives in
      human hair by gas chromatography-mass spectrometry using micro-pulverized
      extraction.
AB  - A gas chromatography-mass spectrometric (GC-MS) method was developed and
      validated for the determination of five psychotropic phenylalkylamine derivatives
      (amphetamine, AP; methamphetamine, MA; 3,4-methylenedioxyamphetamine, MDA; 3,4
      methylenedioxymethamphetamine, MDMA; norketamine, NKT) in human hair. Hair
      samples (10mg) were washed with distilled water and acetone, mechanically
      pulverized for 1.5 min with a bead mill, and then incubated in 1 mL of methanol
      under ultrasonication at 50 degrees C for 1h. The resulting solutions were
      evaporated to dryness, derivatized using heptafluorobutyric anhydride (HFBA) at
      50 degrees C for 30 min, and analyzed by GC-MS. The linear ranges were 0.1-20.0
      ng/mg for AP and MA and 0.05-20.0 ng/mg for MDA, MDMA, and NKT, with the
      coefficients of determination (r(2)>0.9982). The intra-day and inter-day
      precisions were within 11.5% and 12.8%, respectively. The intra-day and inter-day
      accuracies were -4.1% to 5.8% and -6.6% to 4.2%, respectively. The limits of
      detections (LODs) for each compound were lower than 0.028 ng/mg. The recoveries
      were in the range of 78.9-101.2%. Based on these results, the method proved to be
      effective for the rapid and simple determination of phenylalkylamine derivatives
      in hair specimens.

PMID- 20060243
TI  - Assessment of exposure to environmental tobacco smoke in young adolescents
      following implementation of smoke-free policy in Italy.
AB  - We investigated acute and chronic exposure to environmental tobacco smoke (ETS)
      in a cohort of young adolescents using urinary cotinine and hair nicotine testing
      after recent implementation of Italian smoke free legislation. Study subjects
      were 372 Italian young adolescents, between 10 and 16 years of age from the
      principal city of Sicily, Palermo. Urine and hair samples were collected between
      November 2005 and May 2006, when the legislation to ban smoking in all the
      enclosed places of employment (including bars, restaurants, pubs) was completely
      enforced. An exhaustive questionnaire including sociodemographic characteristics
      and active and passive exposure to cigarette smoking was completed. Urinary
      cotinine was analyzed by radioimmunoassay and hair nicotine by a validated GC/MS
      method. Based on urinary cotinine results, 2.1% and 89% of the study
      participants, respectively, showed non-exposure and low acute exposure to ETS,
      whereas only 1.6% presented very high exposure or a hidden active smoking habit
      in the recent past. Hair nicotine disclosed non-exposure and low exposure to ETS
      in 11.8% and 65.6% of the young adolescents, respectively, taking into
      consideration a larger time-window. High repeated exposure, suggesting active
      smoking in some cases was observed in 8.6% of the study subjects. Hair nicotine
      was inversely related to educational level of the adolescents' parents. Overall,
      due to the implementation of smoke-free legislation and information campaign
      against smoking, a significant trend toward low exposure to ETS was observed in
      this study cohort with no association between exposure to ETS and respiratory
      illnesses.

PMID- 20060244
TI  - Interpretation of hair findings in children after methadone poisoning.
AB  - Methadone is not licensed for use in children though it can be employed for the
      management of neonatal opiate withdrawal syndrome. During the last 2 years, our
      laboratory has been asked to test for methadone and EDDP, its major metabolite,
      in hair from children that were admitted to hospital unconscious and where
      methadone had already been identified in a body fluid (4 cases) or where the
      children were deceased and evidence of methadone overdosage having already been
      established (2 cases). In all of these cases, segmental analysis revealed
      approximately the same amount of drug along the hair lock. As a consequence,
      contamination was considered as an issue and interpretation of the results was a
      challenge that deserves particular attention. After decontamination with
      dichloromethane and segmentation the hair was cut into small pieces, incubated
      overnight at 40 degrees C, liquid-liquid extracted and analysed with LC-MS/MS,
      using 2 transitions per compound. The LOQ for both methadone and EDDP was 10
      pg/mg. In the first series involving children admitted to hospital, the following
      results were obtained: * case 1: 4 x 1 cm section, methadone at 0.05-0.08 ng/mg,
      no EDDP detected, * case 2: 4 x 1 cm section, methadone at 0.13-0.15 ng/mg, EDDP
      at 0.02 ng/mg, * case 3: 3 x 1.5 cm section, methadone at 0.07-0.09 ng/mg, EDDP
      at 0.01-0.03 ng/mg, * case 4: 6 x 2 cm section, methadone at 0.06-0.13 ng/mg,
      EDDP at 0.02-0.03 ng/mg. The following concentrations were obtained from the
      children who had died following a methadone overdose: * case 5: 2 x 2 cm section,
      methadone at 0.53-0.58 ng/mg, no EDDP detected, * case 6: 4 x 1 cm section,
      methadone at 0.44-0.77 ng/mg, EDDP at 0.04-0.06 ng/mg. The first observation is
      that all these concentrations are low by comparison with those observed in adults
      on methadone maintenance therapy. However, the more surprising observation is the
      relative homogenous concentrations along the hair locks in each specific case.
      This raises concerns around the possibility that contamination could have
      occurred prior to sampling and makes it hard to reach a conclusion regarding the
      possibility of repeated methadone exposure in the months prior the incidents. In
      these cases it was impossible to conclude that the children were deliberately
      administered methadone. The results of the analysis of hair could indicate that
      they were in an environment where methadone was being used and where the drug was
      not being handled and stored with appropriate care. The homogenous concentrations
      found on segmental analyses could be indicative of external contamination that
      may have arisen not only from direct contamination with the drug but also via
      contamination with body fluids at the post mortem or from sweat produced close to
      the time of the incident. In view of these results we concluded that a single
      determination should not be used firmly to discriminate long-term exposure to a
      drug.

PMID- 20060245
TI  - Exposure to psychoactive substances in women who request voluntary termination of
      pregnancy assessed by serum and hair testing.
AB  - Drug abuse is a worldwide phenomenon with significant health and socioeconomic
      impact and it is of particular concern in women of reproductive age and in
      pregnant women. We aimed to investigate the prevalence of drug use by serum and
      hair testing in a cohort of pregnant women at 12th week gestation who decided
      voluntarily to interrupt their pregnancy and to investigate the relationship
      between drug exposure and induced abortions (IA), repeated IA and contraception.
      The study was conducted in an obstetrics clinic authorised to perform IA in
      Murcia, Spain during an 18 months period (2007-2009). Apart from serum and/or
      hair testing, the 142 women enrolled in the study completed a detailed
      questionnaire regarding drug, alcohol and tobacco use in the previous 3 months.
      Serum and hair samples were analyzed by gas chromatography mass spectrometry
      assays. Hair and serum samples showed a 30% overall positivity to drugs of abuse.
      Of these samples, 20.4, 14.1, 4.2 and 1.4% were positive for cannabinoids,
      cocaine, opiates, and MDMA, respectively, with polydrug use in 5.6% cases. In
      this cohort, a positive association was found between drug use and repeated IA.
      The results highlight the need for promoting pregnancy planning for young women
      in general, especially when consuming psychoactive substances as well as promote
      safe and accessible contraception in women of reproductive age. In women
      requesting IA, specific drug abuse counselling should be implemented.

PMID- 20060246
TI  - Ethyl glucuronide and ethyl sulfate in meconium and hair-potential biomarkers of
      intrauterine exposure to ethanol.
AB  - This study investigated ethyl glucuronide (EtG) and ethyl sulfate (EtS)
      concentration in meconium and in maternal and neonatal hair (HEtG and HFAEEs,
      respectively) as potential markers of intrauterine exposure to ethanol together
      with meconium fatty acid ethyl esters (FAEEs) in a cohort of 99 mother-infant
      dyads, 49 coming from the Arcispedale of Reggio Emilia (Italy) and 50 from the
      Hospital del Mar of Barcelona (Spain). FAEEs, EtG and EtS were measured in
      meconium samples using liquid chromatography-tandem mass spectrometry. A head
      space-solid phase microextraction-gas chromatography-mass spectrometry was used
      to test HEtG and HFAEEs in hair samples from mothers and their newborns. Eighty
      two meconium samples (82.8%) tested positive for EtG, 19 (19.2%) for EtS while 22
      (22.2%) showed FAEEs levels higher than 2 nmol/g, the cut-off used to
      differentiate daily maternal ethanol consumption during pregnancy from occasional
      or no use. Although EtG and EtS in meconium did not correlate with total FAEEs
      concentration, a good correlation between EtG, EtS and ethyl stearate was
      observed. Moreover, EtG correlated well with ethyl palmitoleate, while EtS with
      ethyl laurate, myristate and linolenate. Neither maternal nor neonatal hair
      appears as good predictors of gestational ethanol consumption and subsequent
      fetal exposure in these mother-infant dyads. In conclusion, these data show that
      meconium is so far the best matrix in evaluating intrauterine exposure to
      ethanol, with EtG and EtS being potentially good alternative biomarkers to FAEEs.

PMID- 20060247
TI  - Hair analysis for drugs in driver's license regranting. A Swedish pilot study.
AB  - When being convicted for petty drug offence or driving under the influence of
      drugs in Sweden, the driving license may be suspended. To regain the license, the
      person has to prove that he or she has been drug free during an observation
      period. This is controlled by urine samples taken at several occasions. However,
      the risk of manipulation and the risk of false negative urine samples are high.
      In addition, many people find it difficult or embarrassing to urinate when
      observed. Hair sampling might therefore be a welcome option to this procedure,
      with its easy sampling and minimal risk of manipulation. The longer detection
      window may also provide better information to the physician. The aim of this work
      was to evaluate if clients preferred hair samples to urine and to investigate
      practical and interpretive problems or advantages with hair samples. Ninety-nine
      hair samples and 198 urine samples were collected from 84 clients during the 12
      month study period. Hair samples were divided into either one segment (0-3 cm) or
      two segments (0-3 and 3-6 cm) depending on the length. The hair samples were
      screened with LC-MS-MS for 20 drugs and confirmation of positive results were
      performed with GC-MS or LC-MS-MS. The results were compared to urine samples
      taken at two occasions during the observation period. To cover the timeframe of
      the urine samples hair was collected 2 weeks after the second sample. The urine
      samples were analysed with immunochemical screening and positive results
      confirmed with GC-MS or LC-MS-MS. Seventy-four clients presented with negative
      results in both urine and hair. Hair analysis identified illegal drugs at seven
      different occasions whereas urine failed to identify any illegal drugs. However
      the thresholds used may still be too high to find sporadic use as clients that
      admitted to use drugs sporadically presented with drug concentrations lower than
      the agreed thresholds but above the limit of detection. This implicates that the
      physician must have an understanding and knowledge of the limitations of the
      screening methods used. Another important outcome was that the clients approved
      of hair sampling considering it a better means to prove their drug abstinence. In
      addition, both the clients and the clinicians thought hair sampling easier than
      urine sampling. We believe that hair analysis can offer several advantages
      compared to urine analysis for clinicians working with driving license
      regranting.

PMID- 20060248
TI  - Forensic Science International. Editorial.

PMID- 20060249
TI  - Time-dependent organic changes of intravenous thrombi in stasis-induced deep vein
      thrombosis model and its application to thrombus age determination.
AB  - Using histochemical and immunohistochemical techniques, we examined the
      intrathrombotic collagen contents and the appearance of hemosiderin-positive
      cells, neovessels, and myofibroblasts in a stasis-induced venous thrombosis
      model. The intrathrombotic collagen deposition area occupied about 20% at 5 days,
      and exceeded 80% at 21 days after ligation of the inferior vena cava (IVC).
      Hemosiderin-positive cells in the thrombus first appeared at 3 days in only one
      of the five samples, and positive cells were constantly detected in all thrombi
      at 5 days or later. CD31-positive neovessels in the thrombus first appeared at 5
      days in one of five samples and were detected in all samples after 10 days. At 7
      days, alphaSMA-positive myofibroblasts at the periphery of the thrombus first
      appeared in three of five samples, and were detected and enhanced time
      dependently in all samples after 10 days. These observations demonstrated that
      these markers would be applicable for thrombus age determination.

PMID- 20060250
TI  - Consensus of the Society of Hair Testing on hair testing for chronic excessive
      alcohol consumption 2009.

PMID- 20060251
TI  - A combined a-EEG and MR spectroscopy study in term newborns with hypoxic-ischemic
      encephalopathy.
AB  - OBJECTIVES: Brain damage following a perinatal hypoxic-ischemic (HI) insult has
      been documented by different diagnostic techniques. The aim of the present study
      was to relate a-EEG time course during the first 24h of life to brain metabolic
      changes detected by proton MR spectroscopy ((1)H-MRS) at 7-10days of life and to
      evaluate their correlation with outcome. METHODS: Thirty-two patients with any
      grade HI encephalopathy were studied. Thirty-one out of 32 patients survived and
      underwent (1)H-MRS examination at 7-10days of life; a-EEG was recorded during the
      first 24h of life in 27/32 newborns; 26 patients underwent both examinations.
      Griffiths test, evaluation of motor skills, visual and hearing function were
      performed at regular intervals until the age of 2years. RESULTS: a-EEG at 6, 12
      and 24h of life showed a significant correlation with outcome. N-acetyl
      aspartate/creatine (Cr), Lactate/Cr and myo-inositol differed significantly
      between patients with normal or poor outcome. a-EEG time course during the first
      24h of life showed improvement in newborns with normal (1)H-MRS and good outcome
      and a deterioration in those with abnormal (1)H-MRS and poor outcome.
      CONCLUSIONS: a-EEG time course may be able to document the severity and the
      evolution of the cerebral damage following an HI event. a-EEG is related to the
      severity of cerebral injury as defined by (1)H-MRS and both examinations showed a
      good correlation with outcome. These data, obtained in non-cooled infants, may
      represent reference data for future investigations in cooled infants.

PMID- 20060252
TI  - Migraine in junior high-school students: A prospective 3-academic-year cohort
      study.
AB  - Migraine is a common childhood illness with expected favorable outcome. A study
      of the long-term clinical course of childhood migraine will provide information
      of evolution of migraine. A cohort study for 3-academic-year was conducted in
      Thai junior high-school children from July 2005 to February 2008 to determine the
      clinical course of migraine. Two hundred and forty-eight students in four junior
      high schools diagnosed with migraine according to ICHD-II in July 2005 were
      recruited. Each student was serially evaluated twice yearly from 7th grade during
      each semester of the academic year until the second semester of 9th grade.
      Determination of the characteristics, severity, frequency, and treatment of
      headache were obtained by questionnaire and direct interview. At the final
      evaluation, clinical course of headache was categorized into seven patterns.
      Among enrolled students, 209 (84.3%) completed the study. Twenty-eight (13.5%)
      students had no recurrent headache while that of 153 (73.5%) improved. No
      improvement of migraine and worsened migraine were observed in four students
      (1.8%) and 24 students (11.2%), respectively. Spontaneous remission and avoidance
      of precipitating causes contributed to relief of migraine in the majority of the
      students. Stress-related daily school activities and inadequate rest were
      reported as common precipitating factors among students with non-improving or
      worsening outcome. Chronic daily headache and tension-type headache was observed
      in 6 and 30 students, respectively. This study confirms that clinical course of
      migraine in schoolchildren is benign. Frequency and intensity of headache can be
      reduced with reassurance and appropriate guidance. Early recognition and
      appropriate prevention of migraine attack will decrease the risk of chronic
      migraine and disease burden.

PMID- 20060253
TI  - Characterization of the constituents in rat biological fluids after oral
      administration of Fufang Danshen tablets by ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry.
AB  - An ultra-performance liquid chromatography/quadrupole time-of-flight mass
      spectrometry method was established to detect as many constituents in rat
      biological fluids as possible after oral administration of Fufang Danshen tablets
      (FDTs). A C18 column (1.8microm particle size) was adopted to separate the
      samples, and mass spectra were acquired in both negative and positive modes.
      First, the fingerprints of FDTs were established, resulting in 43 components
      being detected within 25min. Among these compounds, 37 were tentatively
      identified by comparing the retention times and mass spectral data with those of
      reference standards and the reference literature; the other 6 components were
      tentatively assigned solely based on the MS data. In vivo, 14 components and 8
      metabolites of FDT were observed in plasma, and 12 components of FDT were
      detected in urine. Tanshinaldehyde, danshexinkun B, a glycine conjugate of
      danshensu and a methylated conjugate of danshexinkun B were newly detected in rat
      biological fluids. This study developed a high-speed and sensitive method that
      was successfully utilized for screening the active ingredients of a Chinese
      medical formula and provided helpful chemical information for further
      pharmacology and active mechanism research on Chinese medicine.

PMID- 20060254
TI  - Spinal epidural abscess.
AB  - BACKGROUND: Spinal epidural abscess is an uncommon disease with a relatively high
      rate of associated morbidity and mortality. The most important determinant of
      outcome is early diagnosis and initiation of appropriate treatment. OBJECTIVES:
      We aim to highlight the clinical manifestations, describe the early diagnostic
      evaluation, and outline the treatment principles for spinal epidural abscess in
      the adult. DISCUSSION: Spinal epidural abscess should be suspected in the patient
      presenting with complaints of back pain or a neurologic deficit in conjunction
      with fever or an elevated erythrocyte sedimentation rate. Gadolinium-enhanced
      magnetic resonance imaging is the diagnostic modality of choice to confirm the
      presence and determine the location of the abscess. Emergent surgical
      decompression and debridement (with or without spinal stabilization) followed by
      long-term antimicrobial therapy remains the treatment of choice. In select cases,
      non-operative management can be cautiously considered when the risk of neurologic
      complications is determined to be low. CONCLUSION: Patients with a spinal
      epidural abscess often present first in the emergency department setting. It is
      imperative for the emergency physician to be familiar with the clinical features,
      diagnostic work-up, and basic management principles of spinal epidural abscess.

PMID- 20060255
TI  - Using the word 'cancer' in communication about an abnormal Pap test: finding
      common ground with patient-provider communication.
AB  - OBJECTIVE: To investigate provider and patient views about communication
      regarding cervical cancer screening follow-up. METHODS: Using qualitative
      analysis, we interviewed 20 providers and 10 patients from two urban clinics that
      serve low-income African American and Hispanic women. Semi-structured interviews
      and focus groups assessed familiarity with National Cancer Institute's Cancer
      Information Service (CIS) and reactions to a letter asking women with abnormal
      Pap test to telephone CIS. The letter suggested questions to ask prior to
      receiving follow-up. RESULTS: No patient or provider was familiar with CIS.
      Providers but not patients expressed discomfort with use of the word 'cancer' in
      the letter and in CIS's name. Providers feared that reference to cancer would
      provoke fatalism and impede timely follow-up, whereas patients felt information
      about cancer risk was needed to prompt timely follow-up. Information providers
      found necessary to convey in order to accurately explain abnormal Pap tests
      surpassed patients' literacy levels. CONCLUSION: Qualitative data suggest
      important gaps in perspective between providers and patients. There is a need to
      bridge the gap and overcome communication challenges to promote timely medical
      follow-up and have better health outcomes. PRACTICE IMPLICATIONS: Implications
      and strategies for improving patient-provider education and communication about
      abnormal Pap test are discussed.

PMID- 20060256
TI  - Who's in charge? The role of responsibility attribution in self-management among
      people with chronic illness.
AB  - OBJECTIVE: To explore how responsibility attribution influences self-management
      regimens among people with chronic illness. METHODS: This qualitative content
      analysis included 26 interviews with people living with chronic illness. RESULTS:
      The participants attributed responsibility to internal, external or a combination
      of these factors, meaning that they either assumed responsibility for self
      management or considered other people or factors responsible. Internal
      responsibility was associated with a multifaceted self-management regimen,
      whereas external responsibility was related to "conventional" self-management
      such as taking medication, managing symptoms and lifestyle changes. CONCLUSION:
      How responsibility is attributed is vital for the way in which individuals
      perform self-management. In this study, those who attributed responsibility to
      external factors mainly performed recommended behaviours to control their
      illness. In contrast, to take charge of their illness and be an active
      participant in the care, individuals must take responsibility for themselves,
      i.e. internal responsibility. PRACTICE IMPLICATIONS: Health-care providers should
      acknowledge and support individuals' wishes about various levels of
      responsibility as well as different kinds of patient-provider relationships.

PMID- 20060257
TI  - The role of helplessness, outcome expectation for exercise and literacy in
      predicting disability and symptoms in older adults with arthritis.
AB  - OBJECTIVE: To examine the effect of outcome expectation for exercise (OEE),
      helplessness, and literacy on arthritis outcomes in 2 community-based lifestyle
      randomized controlled trials (RCTs) conducted in urban and rural communities with
      older adults with arthritis. METHODS: Data from 391 participants in 2 RCTs were
      combined to examine associations of 2 psychosocial variables: helplessness and
      OEE, and literacy with arthritis outcomes. Arthritis outcomes namely, the Health
      Assessment Questionnaire-Disability Index (HAQ-DI) and arthritis symptoms pain,
      fatigue and stiffness Visual Analogue Scales (VAS), were measured at baseline and
      at the end of the interventions. Complete baseline and post-intervention data
      were analyzed using STATA version 9. RESULTS: Disability after intervention was
      not predicted by helplessness, literacy, or OEE in the adjusted model. Arthritis
      symptoms after the intervention were all significantly predicted by helplessness
      at various magnitudes in adjusted models, but OEE and literacy were not
      significant predictors. CONCLUSION: When literacy, helplessness, and OEE were
      examined as predictors of arthritis outcomes in intervention trials, they did not
      predict disability. However, helplessness predicted symptoms of pain, fatigue,
      and stiffness, but literacy did not predict symptoms. PRACTICE IMPLICATIONS:
      Future sustainable interventions may include self-management components that
      address decreasing helplessness to improve arthritis outcomes.

PMID- 20060258
TI  - Dynamic airway evaluation with volume CT: initial experience.
AB  - PURPOSE: The purpose of the study was to prospectively establish the use of a
      novel multidetector computed tomography unit (MDCT) with 320 x 0.5 detector rows
      for the evaluation of tracheomalacia by using a dynamic expiratory low-dose
      technique. METHODS: Six adult patients (5 men, 1 woman; mean age, 53.7 years [37
      70 years]) referred for a clinical suspicion of tracheomalacia were studied on a
      320-row MDCT unit by using the following parameters: 120 kVp, 40-50 mA, 0.5
      second gantry rotation, and z-axis coverage of 160 mm sufficient to cover the
      thoracic trachea to the proximal bronchi. Image acquisition occurred during a
      forceful exhalation. The image data set was subject to the following analyses:
      cross-sectional area of airway lumen at 4 predefined locations (thoracic inlet,
      aortic arch, carina, and bronchus intermedius) and measurement of airway volume.
      RESULTS: All 6 patients had evidence of tracheomalacia, the proximal trachea
      collapsed at a later phase of expiration (3-4 seconds) than the distal trachea (2
      3 seconds). The most common region of airway collapse occurred at the level of
      the aortic arch (5/6 [83%]), Three patients (50%) had diffuse segmental luminal
      narrowing that involved the tracheobronchial tree. The radiation dose (estimated
      dose length product, computed tomography console) measured 293.9 mGy in 1 subject
      and 483.5 mGy in 5 patients. CONCLUSIONS: Four-dimensional true isophasic and
      isovolumetric imaging of the central airways by using 320-row MDCT is a viable
      technique for the diagnosis of tracheomalacia; it provides a comprehensive
      assessment of airways dynamic.

PMID- 20060259
TI  - Extracardiac findings in cardiac computed tomographic angiography in patients at
      low to intermediate risk for coronary artery disease.
AB  - PURPOSE: To evaluate the prevalence, clinical significance, interobserver
      agreement, and follow-up of extracardiac findings on coronary computed
      tomographic angiography (CTA). METHODS: A prospectively recruited cohort of 80
      patients at low to intermediate risk of having coronary artery disease underwent
      CTA with field of view imaging from lung apices to upper abdomen. Two staff
      radiologists read each scan independently. Scans read by reader no. 1 were read
      as part of routine clinical practice, and the findings were subsequently
      reclassified to potentially significant, as defined by requiring clinical or
      radiologic follow-up, and insignificant by a separate observer, whereas reader
      no. 2 retrospectively read and autonomously classified the findings as
      potentially significant or insignificant. RESULTS: Reader no. 1 found 7
      potentially significant findings in 7 patients and 33 insignificant findings in
      29 patients. Reader no. 2 found 10 potentially significant findings in 10
      patients and 59 insignificant findings in 42 patients. Inter-rater agreement was
      moderate (kappa = 0.49; 95% confidence interval, 0.31-0.67) for the presence vs
      the absence of extracardiac findings and moderate (kappa = 0.52; 95% confidence
      interval, 0.15-0.89) for the presence of potentially significant extracardiac
      findings. The most common potentially significant finding was possibly malignant
      lung nodule (n = 6 [reader 1], 4 [reader 2]). Four patients with potentially
      significant findings received follow-up imaging, and 1 patient underwent biopsy,
      which was complicated by pneumothorax. No diagnoses of malignancy were made.
      CONCLUSIONS: Extracardiac findings are frequent and moderately reproducible,
      however, in this study, not associated with clinical benefit. Large prospective
      studies are required to establish whether reporting of extracardiac findings is
      associated with improved patient outcomes.

PMID- 20060260
TI  - Measurement of carotid stenosis on computed tomographic angiography: reliability
      depends on postprocessing technique.
AB  - PURPOSE: We previously demonstrated the validity of axial source (AxS) image
      quantification of computed tomographic angiography (CTA) visualized carotid
      stenosis. There is concern that AxS images may not accurately measure stenosis in
      patients with obliquely orientated stenosis and that measurements on axial
      oblique (AxO) multiplanar reformats (MPR), maximum intensity projections (MIP)
      images, or Doppler ultrasound (DUS) are superior. We tested the performance of
      AxS images against AxO MPRs, MIPs, and DUS techniques for stenosis
      quantification. METHODS: A total of 120 consecutive patients with CTA and DUS
      detected carotid disease were enrolled; carotids with occlusion, near occlusion,
      or stenosis <40% were excluded. Proximal and distal carotid diameters and North
      American Symptomatic Carotid Endarterectomy Trial (NASCET) style ratios were
      measured independently by 2 neuroradiologists on AxS, AxO, and MIP images on
      separate occasions in a blinded protocol. Intra- and interobserver agreements
      were determined for all measurements. The performance of different image types to
      identify > or =70% stenosis was assessed against a NASCET-style reference
      standard. RESULTS: Intra- and interobserver reliabilities for stenosis
      measurements were higher for both AxS (interclass correlation coefficients [ICC],
      0.87-0.93 and 0.84-0.89) and AxO images (ICCs, 0.82-0.89 and 0.86-0.92) than for
      MIPs (ICCs, 0.66-0.86 and 0.79-0.82), respectively. Intra- and interobserver
      agreements on the NASCET ratio tended to be lower than proximal stenosis
      measurements. AxS and AxO image proximal stenosis measurements most accurately
      distinguished patients with > or =70% stenosis (0.90), followed by DUS (0.83) and
      MIP images (0.76). CONCLUSIONS: A single AxS image stenosis measurement was
      highly reproducible and accurate in the estimation of carotid stenosis, which
      precluded the need for AxO MPRs.

PMID- 20060261
TI  - Practice of sedation and the perception of discomfort during mechanical
      ventilation in Chinese intensive care units.
AB  - PURPOSE: The purpose of this study was to investigate sedation practices and the
      perception of discomfort during mechanical ventilation in Chinese intensive care
      units (ICUs). MATERIAL AND METHOD: A prospective, observational, cohort study was
      conducted in 31 Chinese ICUs in academic hospitals from June 15 to August 15,
      2006. Conscious patients who were discharged from the ICU after mechanical
      ventilation were consecutively included. Using a standardized questionnaire, a
      personal interview was conducted with each patient within 2 days after discharge
      from the ICU. Patients were asked about recollections of emotional and physical
      discomfort. Sedation and analgesia administration data were collected from
      patient records. RESULTS: As prospectively defined, 83 (50.9%) of 163 patients
      met criteria for complex-mixed discomfort (ie, at least 1 emotional and 2
      physical disturbances). Similarly, 79.1% of patients remembered seriously
      uncomfortable experiences associated with 1 of the 3 predefined sources. Both
      protocolized sedation and continuous sedation without a defined protocol, but not
      intermittent sedation, significantly reduced the relative risk of complex-mixed
      discomfort occurrences (P < .001). Notably, only 14.7% of patients received
      protocolized sedation, and 61 (37.4%) of 163 were not given any sedatives.
      CONCLUSION: Mechanically ventilated ICU patients in Chinese academic hospitals
      were inadequately treated for discomfort. Protocolized sedation can effectively
      improve patient comfort.

PMID- 20060262
TI  - A simple linearization of the self-shrinking generator by means of cellular
      automata.
AB  - In this work, it is shown that the output sequence of a well-known cryptographic
      generator, the so-called self-shrinking generator, can be obtained from a simple
      linear model based on cellular automata. In fact, such a cellular model is a
      linear version of a nonlinear keystream generator currently used in stream
      ciphers. The linearization procedure is immediate and is based on the
      concatenation of a basic structure. The obtained cellular automata can be easily
      implemented with FPGA logic. Linearity and symmetry properties in such automata
      can be advantageously exploited for the analysis and/or cryptanalysis of this
      particular type of sequence generator.

PMID- 20060263
TI  - Assessment of texture measures susceptibility to noise in conventional and
      contrast enhanced computed tomography lung tumour images.
AB  - Noise is one of the major problems that hinder an effective texture analysis of
      disease in medical images, which may cause variability in the reported diagnosis.
      In this paper seven texture measurement methods (two wavelet, two model and three
      statistical based) were applied to investigate their susceptibility to subtle
      noise caused by acquisition and reconstruction deficiencies in computed
      tomography (CT) images. Features of lung tumours were extracted from two
      different conventional and contrast enhanced CT image data-sets under filtered
      and noisy conditions. When measuring the noise in the background open-air region
      of the analysed CT images, noise of Gaussian and Rayleigh distributions with
      varying mean and variance was encountered, and Fishers' distance was used to
      differentiate between an original extracted lung tumour region of interest (ROI)
      with the filtered and noisy reconstructed versions. It was determined that the
      wavelet packet (WP) and fractal dimension measures were the least affected, while
      the Gaussian Markov random field, run-length and co-occurrence matrices were the
      most affected by noise. Depending on the selected ROI size, it was concluded that
      texture measures with fewer extracted features can decrease susceptibility to
      noise, with the WP and the Gabor filter having a stable performance in both
      filtered and noisy CT versions and for both data-sets. Knowing how robust each
      texture measure under noise presence is can assist physicians using an automated
      lung texture classification system in choosing the appropriate feature extraction
      algorithm for a more accurate diagnosis.

PMID- 20060264
TI  - Neighborhood socioeconomic status in relation to dietary intake and insulin
      resistance syndrome in female Japanese dietetic students.
AB  - OBJECTIVE: An increasing number of studies in Western countries have shown that
      living in a socioeconomically disadvantaged neighborhood is associated with
      unfavorable dietary intake patterns and health status. However, information on
      such neighborhood socioeconomic differences in diet and health among different
      cultural settings, including Japan, is limited. This cross-sectional study
      examined the association of neighborhood socioeconomic status (SES) with dietary
      intake and a summary score of the insulin resistance syndrome (IRS) in a group of
      young Japanese women. METHODS: Subjects were 1081 female Japanese dietetic
      students aged 18 to 22 y residing in 295 municipalities in Japan. Neighborhood
      SES index was defined by seven municipal-level variables, namely unemployment,
      household overcrowding, poverty, education, income, home ownership, and
      vulnerable group, with an increasing index signifying increasing neighborhood
      socioeconomic disadvantage. Dietary intake was estimated using a validated,
      comprehensive self-administered diet-history questionnaire. Measurements of body
      mass index, systolic blood pressure, fasting high-density lipoprotein
      cholesterol, triacylglycerol, glucose, and insulin were combined into an IRS
      score, with an increasing score signifying increasing levels of components of the
      IRS. RESULTS: Neighborhood SES index was not associated with most of the dietary
      variables, body mass index, high-density lipoprotein cholesterol,
      triacylglycerol, or glucose. However, neighborhood SES index was significantly
      positively associated with systolic blood pressure, insulin, and IRS score, after
      adjustment for potential confounding or mediating factors, including household
      SES, dietary, and lifestyle factors. CONCLUSION: Neighborhood socioeconomic
      disadvantage was associated with unfavorable profiles of the IRS score, but not
      dietary intake, in a group of young Japanese women.

PMID- 20060265
TI  - Large osteochondroma of the mandibular condyle treated by condylectomy using a
      transzygomatic approach.
AB  - This article presents an interesting case of osteochondroma of the mandibular
      condyle with multiple projections in a 42-year-old man. Owing to the large size
      of the lesion, surgical condylectomy was performed using a transzygomatic
      approach.

PMID- 20060266
TI  - Octacalcium phosphate (OCP) collagen composites enhance bone healing in a dog
      tooth extraction socket model.
AB  - The authors have reported that a scaffold constructed of synthetic octacalcium
      phosphate (OCP) and porcine atelocollagen sponge (OCP/Col) enhanced bone
      regeneration more than sintered beta-tricalcium phosphate collagen composite or
      sintered hydroxyapatite collagen composite with a rat calvarial defect model. To
      aim for clinical application, the present study investigated whether OCP/Col
      would enhance bone healing in a dog tooth extraction socket model. Six adult,
      male, beagle dogs were used. The tooth extraction socket model was made by
      extracting bilateral third maxillary incisors and the subsequent removal of
      buccal bone. Disks of OCP/Col were implanted into one side of the model and the
      other side was untreated. The specimens were fixed 1 or 3 months after
      implantation. In radiographic analysis, the OCP/Col-treated group showed a wider
      range of radiopacity than the untreated control. Histologically, the OCP/Col
      treated group showed more abundant newly formed bone than untreated control, and
      the implanted OCP was gradually resorbed. In morphometrical analysis, enlargement
      of the buccal alveolus in the OCP/Col group was significantly greater than in the
      untreated control. This study showed that implanted OCP/Col would be replaced by
      newly formed bone and OCP/Col implantation would enhance bone healing in a tooth
      socket model.

PMID- 20060267
TI  - CD147/basigin promotes progression of malignant melanoma and other cancers.
AB  - CD147/basigin, a transmembrane protein belonging to the immunoglobulin super
      family, was originally cloned as a carrier of Lewis X carbohydrate antigen. CD147
      is strongly related to cancer progression; it is highly expressed by various
      cancer cells including malignant melanoma (MM) cells and it plays important roles
      in tumor invasiveness, metastasis, cellular proliferation, and in vascular
      endothelial growth factor (VEGF) production, tumor cell glycolysis, and multi
      drug resistance (MDR). CD147 on cancer cells induces matrix metalloproteinase
      expression by neighboring fibroblasts, leading to tumor cell invasion. In a nude
      mouse model of pulmonary metastasis from MM, the metastatic potential of CD147
      expressing MM cells injected into the tail vein is abolished by CD147 silencing.
      CD147 enhances cellular proliferation and VEGF production by MM cells; it
      promotes tumor cell glycolysis by facilitating lactate transport in combination
      with monocarboxylate transporters, resulting in tumor progression. CD147 is
      responsible for the MDR phenotype via P-glycoprotein expression. These findings
      strongly suggest CD147 as a possible therapeutic target for overcoming metastasis
      and MDR, major obstacles to the effective treatment of malignant cancers.

PMID- 20060268
TI  - Targeting to the hair follicles: current status and potential.
AB  - The pilosebaceous unit is a complex structure that undergoes a specific growth
      cycle and comprises a few important drug targeting sites. For example, drugs can
      be targeted to the bulge region with stem cells or to the sebaceous glands.
      Interest in pilosebaceous units is directed towards their utilization as
      reservoirs for localized therapy and also as a transport pathway for systemic
      drug delivery. Improved investigative methods, such as differential stripping,
      are being developed in order to determine follicular penetration. This article
      reviews relevant aspects of effective follicle-targeting formulations and
      delivery systems as well as the activity status of hair follicles, and variations
      in follicle size and distribution throughout various body regions. Each of these
      factors strongly affects follicular permeation. We provide examples of improved
      penetration of particle-based formulations and of a size-dependent manner of
      follicular penetration. Contradictions are also discussed, indicating the need
      for detailed future investigations.

PMID- 20060269
TI  - Mutational survey of recessive dystrophic epidermolysis bullosa in Tunisian
      families unveils a spectrum of private, ethnic specific and world wide recurrent
      mutations.

PMID- 20060270
TI  - Glycolic acid induces keratinocyte proliferation in a skin equivalent model via
      TRPV1 activation.
AB  - BACKGROUND: Glycolic acid (GA) is the most commonly used alpha-hydroxy acid (AHA)
      for dermatologic applications, and is considered as a versatile superficial
      peeling agent for facial rejuvenation. Its therapeutic effect includes
      acceleration of epidermal turnover without apparent inflammation, and its action
      is pH-dependent. However, little is known about the molecular mechanism of GA
      induced peeling. OBJECTIVE: To investigate the effects of topical application of
      GA on cell proliferation using a skin equivalent model and to examine the
      molecular mechanisms of GA-induced peeling. METHODS: GA solution was applied on
      the surface of a skin equivalent model, and cell proliferation was measured by
      means of BrdU-incorporation and immunohistochemical methods. Release of chemical
      mediators such as ATP into the medium was examined. The effects of antagonists of
      ion channels were also analyzed. RESULTS: At 24h after GA application, BrdU
      incorporation into basal keratinocytes was significantly increased. Induction of
      keratinocyte proliferation was pH-dependent, and was inhibited by antagonists of
      TRPV1, an acid-sensitive ion channel. Furthermore, transient ATP release was
      detected in the culture medium after GA stimulation, and this was also suppressed
      by TRPV1 antagonists. CONCLUSION: These results suggest that one of the
      mechanisms of GA-induced epidermal proliferation is a growth response of basal
      keratinocytes to the local elevation of H(+)-ion concentration by infiltrated GA.
      This response is mediated by TRPV1 activation and ATP release. Activation of P2
      receptors by the released ATP may also be involved.

PMID- 20060271
TI  - Cutaneous consequences of inhibiting EGF receptor signaling in vivo: normal hair
      follicle development, but retarded hair cycle induction and inhibition of
      adipocyte growth in Egfr(Wa5) mice.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) network is essential for
      proper development and homeostasis of skin and hair. However, detailed dissection
      of the role of the EGFR in hair follicle development and cycling have been
      impaired by the early mortality of EGFR knockout mice. OBJECTIVES: We have
      studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfr(wa5)), whose
      product acts as a dominant-negative receptor, whether strongly reduced EGFR
      signaling impacts on the hair and skin phenotype. METHODS: Histomorphometry and
      immunohistochemistry were employed to study hair follicle morphogenesis stages
      and cycle induction in Waved-5 mice and control littermates during embryonic
      development and postnatal life. RESULTS: By routine histology and quantitative
      histomorphometry, no significant abnormalities in the epidermis and in hair
      follicle morphogenesis were detected, while the initiation of hair follicle
      cycling was slightly, but significantly retarded. Proliferation and apoptosis of
      epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered.
      Intriguingly, the thickness of the subcutis and the percentage of proliferating
      subcutaneous adipocytes were significantly reduced in Waved-5 mice around days
      P8.5 to P10.5. Although no differences in total body weight gain could be
      detected, Wa5 mice showed a significant reduction in the percentage of body fat
      at P8.5. CONCLUSION: Our results suggest the presence of effective compensatory
      mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair
      follicle keratinocyte function despite very low levels of EGFR-mediated
      signaling. Our unexpected findings of transiently reduced subcutaneous adipose
      tissue indicate a role for the EGFR in regulating subcutaneous fat.

PMID- 20060272
TI  - Association of single nucleotide polymorphisms in the IL-12 (IL-12A and B) and IL
      12 receptor (IL-12Rbeta1 and beta2) genes and gene-gene interactions with atopic
      dermatitis in Koreans.
AB  - BACKGROUND: The acute skin lesions of atopic dermatitis (AD) are associated with
      Th2 cells; however, the chronic skin lesions of AD are associated with Th1 cells
      via the action of IL-12. OBJECTIVE: We evaluated the associations of single
      nucleotide polymorphisms (SNPs) and haplotype in the IL-12 and IL-12 receptor
      genes, and determined the gene-gene interactions between the SNPs of these genes
      and the SNPs of the IL-18 gene that we previously reported. METHOD: We genotyped
      24 SNPs from 4 IL-12/IL-12R genes for 1089 case-control samples (631 AD patients
      and 458 normal controls). We measured the serum IL-12 concentrations in 89
      individuals (79 AD patients and 10 controls) by ELISA. We analyzed the SNPs and
      haplotypes in each gene and also searched for the gene-gene interactions. RESULT:
      The rs582504 (IVS-798A/T) SNP and the haplotype TA (rs582054 and rs2243151) in
      the IL-12A gene, and the rs438421 (IVS12+1266T/C) SNP and the haplotype CCA
      (rs375947, rs438421, and rs1870063) in the IL-12RB1 gene were significantly
      associated with the AD phenotype. We showed that the rs438421 polymorphism in the
      IL-12RB1 (TT) gene and the rs2066446 polymorphism in the IL-12RB2 (AA) gene had a
      significant interaction to develop the ADe phenotype (allergic type of AD), and
      those individuals with the risk alleles, TT/AA/CC (IL-12RB1/IL-12RB2/IL-18), have
      more than a 10-fold increased risk to develop ADe. CONCLUSION: This study
      provides evidence for a significant interaction between the IL-12RB1 and IL-12RB2
      genes that contribute to a 4-fold increased risk for developing ADe. In addition
      to the IL-12R interaction, we suggest that the IL-18 gene can significantly
      interact with the IL-12R gene to develop ADe. In addition to the interaction, the
      SNPs and haplotypes in the IL-12A and IL-12RB1 genes are independently and
      significantly associated with the AD phenotype, and especially with the ADe
      phenotype. This data may contribute to our understanding of AD genetic
      interactions and account for the additional risk of certain patients to develop
      AD.

PMID- 20060273
TI  - Molecular epidemiology of Escherichia coli producing CTX-M beta-lactamases: the
      worldwide emergence of clone ST131 O25:H4.
AB  - Since 2000, Escherichia coli producing CTX-M enzymes have emerged worldwide as
      important causes of community-onset urinary tract and bloodstream infections
      owing to extended-spectrum beta-lactamase (ESBL)-producing bacteria. Molecular
      epidemiological studies suggested that the sudden worldwide increase of CTX-M-15
      producing E. coli was mainly due to a single clone (ST131) and that foreign
      travel to high-risk areas, such as the Indian subcontinent, might in part play a
      role in the spread of this clone across different continents. Empirical
      antibiotic coverage for these resistant organisms should be considered in
      community patients presenting with sepsis involving the urinary tract, especially
      if the patient recently travelled to a high-risk area. If this emerging public
      health threat is ignored, it is possible that the medical community may be
      forced, in the near future, to use carbapenems as the first choice for the
      empirical treatment of serious infections associated with urinary tract
      infections originating from the community.

PMID- 20060274
TI  - Preparation of stable dispersion of barium titanate nanoparticles: Potential
      applications in biomedicine.
AB  - Nanoscale structures and materials have been explored in many biological
      applications because of their extraordinary novel properties. Here we propose a
      study of cellular interactions with barium titanate nanoparticles, an interesting
      ceramic material that has received a lot of interest in the nanotechnology
      research, but without any attention about its biological potential. We introduced
      for the first time an efficient method for the preparation of stable aqueous
      dispersions of barium titanate nanoparticles, characterized with FIB, TEM and AFM
      imaging, light scattering, Z-potential and UV/vis analysis. Finally, we presented
      a systematic study of short-term cytotoxicity of the prepared dispersion based
      both on quantitative (metabolism, proliferation) and qualitative (apoptosis,
      viability, differentiation) assays.

PMID- 20060275
TI  - Lipid/particle assemblies based on maltodextrin-gum arabic core as bio-carriers.
AB  - A novel system to carry and protect epigallocatechin gallate (EGCG), an
      antioxidant from the green tea, is reported. The system consists of maltodextrin
      and gum arabic nanoparticles coated with egg-yolk l-alpha-phosphatidylcholine
      (Egg-PC)/stearylamine (SA) bilayers. In this study, the polysaccharide core was
      produced by homogenization followed by spray-drying. The lipid coating was
      performed by the lipid film hydration method. The polysaccharide core revealed
      negative zeta potential, which changed to opposite signs after lipid coating. The
      presence of lipid layers was evidenced by cryogenic-transmission (cryo-TEM) and
      scanning (cryo-SEM) electron microscopy studies. An increase in size was observed
      after lipid coating as determined by dynamic light scattering (DLS). Atomic force
      microscopy (AFM) demonstrated that the polysaccharide core provides high
      resistance to mechanical strength. The lipid/particle assemblies show high
      retention efficiency of EGCG at physiological pH, opening the possibility of
      their use for delivery and controlled release of tea catechins.

PMID- 20060276
TI  - Chemical correlation between Gegen Qinlian dispensing granule and its four raw
      herbs by LC fingerprint.
AB  - Gegen Qinlian dispensing granule, a favorite composite formula, is a combination
      of Radix Puerariae Lobatae, Radix Scutellariae, Rhizoma Coptidis and Radix et
      Rhizoma Glycyrrhizae Praeparata cum Melle. To develop a method to overall
      evaluate correlation between the formula and its four raw herbs, LC fingerprints
      of the formula and its raw herbs were developed and LC-DAD-MS was employed to
      identify the components in the formula fingerprint. According to the
      characteristic fragmentation behavior of known flavonoids, alkaloids and saponins
      isolated from the four raw herbs as well as retention time, UV and MS data of
      detected compounds, a total of 23 constituents in the formula fingerprint were
      structurally characterized. Chemical correlation between the formula and the four
      crude herbs was evaluated qualitatively and quantitatively by the developed LC
      fingerprints. The results showed that 8 components in the formula fingerprint
      were addressed to Radix Puerariae Lobatae, 11 to Radix Scutellariae, 7 to Rhizoma
      Coptidis, 3 to Radix et Rhizoma Glycyrrhizae Praeparata cum Melle, and that the
      relative area ratios of the common peaks in the formula vary slightly in
      comparison with corresponding ratios in its crude herbs, demonstrating the
      chemical constituents in the formula have patterns similar to those in its crude
      herbs.

PMID- 20060278
TI  - Localisation and trafficking of Toll-like receptors: an important mode of
      regulation.
AB  - In recent years the importance of the localisation and trafficking of Toll-like
      receptors (TLRs) and their adaptors within the cell has become apparent.
      Localisation and trafficking of both cell surface and endosomal TLRs, alongside
      their adaptors, appears to play an important role not only in ligand recognition
      but also in the downregulation of signaling following ligand stimulation.
      Chaperones, such as gp96, PRAT4A and Unc93B1 play a role in TLR localisation.
      TLR4 cycles between the Golgi and the plasma membrane until engaged by LPS. The
      MyD88-dependent pathway is then initiated at the plasma membrane, followed by the
      movement of the TLR4 complex into the endosome where the MyD88-independent
      pathway is activated. Several proteins, including Triad3A and TAG appear to be
      involved in the movement of TLR4 to the lysosome for degradation.

PMID- 20060277
TI  - Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior
      cingulate cortex of individuals with major depressive disorder.
AB  - Accumulating evidence finds a relative deficiency of peripheral membrane fatty
      acids in persons with affective disorders such as unipolar and bipolar
      depression. Here we sought to investigate whether postmortem brain fatty acids
      within the anterior cingulate cortex (BA-24) varied according to the presence of
      major depression at the time of death. Using capillary gas chromatography we
      measured fatty acids in a depressed group (n=12), and in a control group without
      lifetime history of psychiatric diagnosis (n=14). Compared to the control group,
      the depressed group showed significantly lower concentrations of numerous
      saturated and polyunsaturated fatty acids including both the n-3 and n-6 fatty
      acids. Additionally, significant correlations between age at death and precursor
      (or metabolites) in the n-3 fatty acid pathway were demonstrated in the depressed
      group but not in control subjects. In the n-6 fatty acid family, the ratio of
      20:3(n-6)/18:2(n-6) was higher in patients than in control groups, whereas the
      ratio of 20:4(n-6)/20:3(n-6) was relatively decreased in patients. Lastly, a
      significant negative correlation between age and the ratio of 20:4(n-6) to 22:6(n
      3) was found in patients, but not in controls. Taken together, decreases in
      22:6(n-3) may be caused, at least in part, by the diminished formation of 20:5(n
      3), which is derived from 20:4(n-3) through a Delta5 desaturase reaction. The
      present findings from postmortem brain tissue raise the possibility that an
      increased ratio of 20:4(n-6) to 22:6(n-3) may provide us with a biomarker for
      depression. Future research should further investigate these relationships.

PMID- 20060280
TI  - Influence of different processing techniques on the mechanical properties of used
      tires in embankment construction.
AB  - Use of the processed used tires in embankment construction is becoming an
      accepted way of beneficially recycling scrap tires due to shortages of natural
      mineral resources and increasing waste disposal costs. Using these used tires in
      construction requires an awareness of the properties and the limitations
      associated with their use. The main objective of this paper is to assess the
      different processing techniques on the mechanical properties of used tires-sand
      mixtures to improve the engineering properties of the available soil. In the
      first part, a literature study on the mechanical properties of the processed used
      tires such as tire shreds, tire chips, tire buffings and their mixtures with sand
      are summarized. In the second part, large-scale direct shear tests are performed
      to evaluate shear strength of tire crumb-sand mixtures where information is not
      readily available in the literature. The test results with tire crumb were
      compared with the other processed used tire-sand mixtures. Sand-used tire
      mixtures have higher shear strength than that of the sand alone and the shear
      strength parameters depend on the processing conditions of used tires. Three
      factors are found to significantly affect the mechanical properties: normal
      stress, processing techniques, and the used tire content.

PMID- 20060281
TI  - Reduction of CO(2)-emissions by using biomass in combustion and digestion plants.
AB  - Climate protection is one of the main aims of environmental policy. One way to
      advance and push the progress is to reduce the use of fossil fuels for energy
      production through an increasing production of renewable and CO(2)-neutral energy
      for example through application of biomass. This paper sets the focus on biomass
      streams that can be used both thermal and biological for energy production like
      grass or energy crops. To calculate the potentials of decrease of CO(2)-emissions
      for treatment of biomass in either combustion or digestion plants some scenarios
      were set up with different assumptions regarding degree of efficiency of
      treatment plants which depends on size of plants and the treatment process
      itself. The energetic utilisation of the considered biomass streams is divided in
      different utilisation scenarios: combined heat and power generation (CHP) and
      heat generation or power generation only. Additionally four groups of plant sizes
      referring to electrical power (from 0.1 up to 10.0MW) were taken into
      consideration. The calculations of potential savings of CO(2)-emission in both
      types of treatment scenarios lead to the result that in comparison to biological
      technologies thermal processes show a much higher utilisation of the energy
      content in biomass.

PMID- 20060279
TI  - The innate immune response in leprosy.
AB  - Investigation into the innate immune response in leprosy has provided insight
      into immunoregulation in human infectious disease. Key advances include the role
      of pattern recognition receptors in recognizing pathogen-associated molecular
      patterns of Mycobacterium leprae, cytokine release by innate immune cells,
      macrophage and dendritic cell differentiation, as well as antimicrobial effector
      pathways. These insights provide targets for therapeutic intervention in
      modulating the course of leprosy and other chronic infectious diseases.

PMID- 20060282
TI  - Electrochemical nanobiosensor for express diagnosis of acute myocardial
      infarction in undiluted plasma.
AB  - The myocardial infarction biomarker myoglobin was quantified at the biological
      level in undiluted plasma using developed electrochemical nanosensors with
      immobilized anti-myoglobin. Method for cardiac myoglobin detection is based on
      direct electron transfer between Fe(III)-heme and electrode surface modified with
      gold nanoparticles/didodecyldimethylammonium bromide (DDAB/Au) and antibodies.
      The procedure of myoglobin detection was optimized (pH, incubation times and
      characteristics of electrodes) to express determination of the marker in serum or
      plasma. Plasma of healthy donors and patients with acute myocardial infarction
      (AMI) was analyzed using electrochemical immunosensors and RAMP immunoassay.
      Square wave voltammetry cathodic peak of cardiac myoglobin reduction was found to
      be proportional to myoglobin quantity in plasma as determined by RAMP. The method
      proposed does not require signal enhancement or amplification; nor does it
      require labeled secondary antibodies. Immunosensor has a detection limit of 10
      ng/ml (0.56 nM) and a broad range of working concentrations (10-1780 ng/ml; 0.56
      100 nM). The whole procedure takes 30 min and can be used for express diagnosis
      of acute myocardial infarction.

PMID- 20060283
TI  - Amperometric catechol biosensor based on polyaniline-polyphenol oxidase.
AB  - A novel catechol biosensor was described based on the immobilization of
      polyphenol oxidase (PPO) into polyaniline (PANI), which was easily constructed by
      direct electropolymerization of aniline in a solution containing ionic liquid, 1
      ethyl-3-methylimidazolium ethyl sulfate (EMIES). The developed biosensor for the
      detection of catechol has a linear range of 1.25-150 micromol dm(-3). The maximum
      response current (I(max)) and the Michaelis-Menten constant (k'(m)) are 0.62
      microA and 146 micromol dm(-3), respectively. The activation energy (E(a)) of the
      PPO catalytic reaction is 31.1 kJ mol(-1) in the B-R buffer. The biosensor shows
      good reproducibility (a relative standard deviation of 3.1% was obtained) and
      remarkable long-term stability (it retains 75% of the original activity after
      four months). The effects of potential and pH on the response current of the
      biosensor are also described.

PMID- 20060284
TI  - Electrochemical monitoring of hydrogen peroxide released from leucocytes on
      horseradish peroxidase redox polymer coated electrode chip.
AB  - We developed an electrochemical-sensing device for continuous monitoring
      extracellular hydrogen peroxide (H(2)O(2)). The device consists of an indium-tin
      oxide electrode coated with osmium-polyvinylpyridine gel polymer containing
      horseradish peroxidase (Os-HRP) and a poly-dimethyl siloxane well to house the
      cells on the chip. Granulocyte-like differentiated HL-60 cells were accommodated
      in the well and stimulated with phorbol 12-myristate 13-acetate (PMA), which
      triggered the generation of H(2)O(2). The extracellular H(2)O(2) released from
      the cells was enzymatically reduced at the Os-HRP-modified electrode chip using
      Os(II) as an electron donor, resulting in reduction current responses by the
      device. The reduction current increased immediately upon PMA stimulation and this
      current transient was similar to that obtained by conventional chemiluminescence
      assays using sodium luminol. Apocynin, an inhibitor of NADPH oxidase activation,
      eliminated both the electrochemical and chemiluminescence signals. On the other
      hand, superoxide dismutase (SOD) increased the amperometric signals and catalase
      (CAT) decreased, whereas SOD decreased luminescence emission and CAT did not.
      These results were in accordance with the expected reaction mechanism, and
      strongly indicate that this new electrochemical-sensing device successfully
      detects extracellular H(2)O(2) production.

PMID- 20060285
TI  - Breast cancer genomes--form and function.
AB  - This review summarizes advances in our understanding of the genomic and
      epigenomic abnormalities in breast cancers that are being revealed by the
      increasingly powerful suite of genomic analysis technologies. It summarizes the
      remarkable genomic heterogeneity that characterizes the disease, describes
      mechanisms that shape cancer genomes as they evolve toward metastasis, summarizes
      important recurrent aberrations that exist in spite of the genomic chaos and that
      contribute to breast cancer pathophysiology, and describes the use of preclinical
      models to identify drugs that will be effective against subsets of breast cancers
      carrying specific genomic and epigenomic abnormalities.

PMID- 20060286
TI  - The dynamic ubiquitin ligase duo: Cdh1-APC and Cdc20-APC regulate neuronal
      morphogenesis and connectivity.
AB  - The proper development and patterning of axons, dendrites, and synapses is
      essential for the establishment of accurate neuronal circuits in the brain. A
      major goal in neurobiology is to identify the mechanisms and principles that
      govern these fundamental developmental events of neuronal circuit formation. In
      recent years, exciting new studies have suggested that ubiquitin signaling
      pathways may play crucial roles in the control of neuronal connectivity. Among E3
      ubiquitin ligases, Cdh1-anaphase promoting complex (Cdh1-APC) and Cdc20-APC have
      emerged as key regulators of diverse aspects of neuronal connectivity, from axon
      and dendrite morphogenesis to synapse differentiation and remodeling.

PMID- 20060287
TI  - Anthocyanin-rich red grape extract impedes adenoma development in the Apc(Min)
      mouse: pharmacodynamic changes and anthocyanin levels in the murine biophase.
AB  - PURPOSE: Red grape pomace extract (oenocyanin) is a cheap and rich source of
      anthocyanins, the agents suggested to possess cancer chemopreventive properties.
      Here the hypothesis was tested that oenocyanin added to the diet can interfere
      with intestinal adenoma development in the Apc(Min) mouse, a model of intestinal
      carcinogenesis linked to an Apc mutation. METHODS: Mice received oenocyanin
      (0.3%) in their diet until week 16, when adenoma number and burden were recorded.
      Expression of Akt and ERK proteins was studied by Western blot in adenomas to
      discover effects of anthocyanins on cellular signalling via the PI3 and MAP
      kinase pathways. Levels of anthocyanins were measured by HPLC with visible
      spectroscopic or mass spectrometric detection. RESULTS: In mice which had
      consumed oenocyanin, overall adenoma burden was halved and adenoma number was
      marginally reduced when compared with mice on control diet. The proliferation
      index in colonic adenomatous crypts, as reflected by Ki-67 staining, was
      significantly decreased from 88.14% in control mice to 75.6+/-4% in mice on
      oenocyanin (P=0.014). Expression of Akt in small intestinal adenomas from
      Apc(Min) mice on oenocyanin was reduced by 54% (P=0.003), when compared to
      controls. Oenocyanin anthocyanins and glucuronide metabolites were found in the
      urine and intestine but not in plasma. CONCLUSIONS: The results suggest that
      oenocyanin may be a viable and economical alternative to anthocyanin-rich berry
      extracts for chemopreventive intervention. Akt and pErk might be suitable
      biomarkers of anthocyanin target organ efficacy.

PMID- 20060288
TI  - A randomised phase II study of combination chemotherapy with epirubicin,
      cisplatin and capecitabine (ECX) or cisplatin and capecitabine (CX) in advanced
      gastric cancer.
AB  - BACKGROUND: Both cisplatin/capecitabine (CX) and epirubicin plus CX (ECX) have
      clearly demonstrated efficacy against advanced gastric cancer (AGC). METHODS:
      Chemotherapy-naive patients with histologically confirmed, measurable AGC were
      randomised to receive CX (cisplatin 75mg/m(2) iv on day 1 and capecitabine
      1000mg/m(2) bid po on days 1-14) or ECX (epirubicin 50mg/m(2) plus CX) every
      3weeks. The primary endpoint was progression-free survival (PFS). RESULTS: Of the
      91 registered patients, 45 patients were treated with CX and 44 with ECX. A total
      of 241 CX (median, 6; range, 1-12) and 201 ECX (median, 5; range, 1-11) cycles
      were delivered. Treatment duration was similar for both arms (4.4 for CX versus
      4.2months for ECX). There was no relevant difference in the occurrence of overall
      grade 3 or 4 toxicities between the CX and ECX arms (80% versus 78%,
      respectively; P=0.516). However, none in the CX and 12% in the ECX arm
      discontinued treatment because of toxicity. There were no significant differences
      in therapeutic efficacy between CX and ECX with respect to the response rate (38%
      versus 37%, respectively) and PFS (6.4 versus 6.5months). CONCLUSION: Both CX and
      ECX appear to be active as first-line chemotherapy for AGC, and the safety
      profiles are acceptable. Given the comparable efficacy results, CX could be a
      reasonable standard chemotherapy for untreated AGC patients.

PMID- 20060289
TI  - Allothermal steam gasification of biomass in cyclic multi-compartment bubbling
      fluidized-bed gasifier/combustor - new reactor concept.
AB  - A new reactor concept of allothermal cyclic multi-compartment fluidized bed steam
      biomass gasification is proposed and analyzed numerically. The concept combines
      space and time delocalization to approach an ideal allothermal gasifier.
      Thermochemical conversion of biomass in periodic time and space sequences of
      steam biomass gasification and char/biomass combustion is simulated in which the
      exothermic combustion compartments provide heat into an array of interspersed
      endothermic steam gasification compartments. This should enhance unit heat
      integration and thermal efficiency and procure N(2)-free biosyngas with recourse
      neither to oxygen addition in steam gasification nor contact between flue and
      syngas. The dynamic, one-dimensional, multi-component, non-isothermal model
      developed for this concept accounts for detailed solid and gas flow dynamics
      whereupon gasification/combustion reaction kinetics, thermal effects and
      freeboard-zone reactions were tied. Simulations suggest that allothermal
      operation could be achieved with switch periods in the range of a minute
      supporting practical feasibility for portable small-scale gasification units.

PMID- 20060290
TI  - Quantification and comparison of ammonia-oxidizing bacterial communities in MBRs
      treating various types of wastewater.
AB  - The community structure and abundance of ammonia-oxidizing bacteria (AOB) in
      membrane bioreactors (MBRs) constructed to treat different types of wastewater
      were analyzed by PCR-DGGE, cloning of 16S rRNA fragments and quantitative real
      time PCR techniques. DGGE analysis revealed that the diversity of the ammonia
      oxidizing bacterial communities was similar among the four reactors.
      Additionally, variation in influents had no significant effect on the
      distribution of the AOB communities. Sequencing analysis of screened clones
      revealed a wide variety of nitrifying organisms and denitrifying bacteria, which
      suggests that there may be multiple modes of nitrification and denitrification in
      MBRs. Real-time PCR revealed that the AOB comprised less than 0.1% of the total
      bacteria in all MBRs. The free ammonia content of the influent was well
      correlated with the AOB cell numbers. Taken together, these data suggest that
      higher NH(4)(+)-N content favors the growth of ammonia oxidizers in MBRs.

PMID- 20060291
TI  - Production of bio-fuels (hydrogen and lipids) through a photofermentation
      process.
AB  - The purple non-sulfur photosynthetic bacteria Rhodopseudomonas palustris (strain
      42OL) was investigated for a co-production of both bio-H(2) and biodiesel
      (lipids). The investigation was carried out using malic and glutamic acids in a
      fed-batch cultivation system under continuous irradiances of 36, 56, 75, 151,
      320, 500, and 803 W m(-2). Boltzmann's sigmoidal regression model was used to
      determine growth kinetic parameters during hydrogen photoevolution. The upper
      limit of volumetric hydrogen photoevolution was 15.5 + or - 0.9 ml l(-1) h(-1).
      During the entire cultivation period (408 h), the highest average hydrogen
      production rate (HPR(av)) of 11.1 + or - 3.1 ml l(-1) h(-1) was achieved at an
      irradiance of 320 W m(-2). Biomasses stored at the end of each experimental set
      were analyzed in order to determine lipid content, which ranged from a minimum of
      22 + or - 1% to a maximum of 39 + or - 2% of biomass dry weight.

PMID- 20060292
TI  - Stimulation of in vitro anaerobic oxidation of methane rate in a continuous high
      pressure bioreactor.
AB  - Anaerobic oxidation of methane coupled to sulphate reduction (SR-AOM) prevents
      oceanic methane emissions and is considered as a major environmental process in
      the deep-sea sediments. To stimulate in vitro SR-AOM activity, we designed a
      (continuous) high-pressure bioreactor system. Fed-batch mode incubations showed
      that the elevated methane pressure stimulated SR-AOM activity: when the methane
      pressure increased from 1 to 4.5 to 8 MPa, the initial SR-AOM activity increased
      from 3.46 to 8.64 to 9.22 micromol sulphide production/g(dw)/day; the apparent
      affinity (K(m)) for methane was 37 mM. However, in each fed-batch mode
      incubation, there was an inhibitory effect observed after 2 days, probably due to
      the accumulation of sulphide and the increase of pH. When the reactor was
      operated in a continuous mode, the SR-AOM activity was constantly increasing
      within 18 days at both 1 and 8 MPa pressures.

PMID- 20060293
TI  - Methyl ester of [Maclura pomifera (Rafin.) Schneider] seed oil: biodiesel
      production and characterization.
AB  - Oil extracted from seeds of Maclura pomifera fruits grown in Tunisia was
      investigated as an alternative feedstock for the production of biodiesel fuel.
      Biodiesel was prepared by transesterification of the crude oil with methanol in
      the presence of NaOH as catalyst. Maximum oil to ester conversion was 90%. The
      viscosity of the biodiesel oil (4.66 cSt) is similar to that of petroleum diesel
      (2.5-3.5 cSt). The density (0.889 g/cm(3)), kinematic viscosity (4.66 cSt), flash
      point (180 degrees Celsius), iodine number (125 degrees Celsius), neutralization
      number (0.4), pour point (-9 degrees Celsius), cloud point (-5 degrees Celsius),
      cetane number (48) are very similar to the values set forth by the ASTM and EN
      biodiesel standards for petroleum diesel (No. 2). The comparison shows that the
      methyl esters of M. pomifera oil could be possible diesel fuel replacements.

PMID- 20060294
TI  - Novel 3-aminopyrazole inhibitors of MK-2 discovered by scaffold hopping strategy.
AB  - New, selective 3-aminopyrazole based MK2-inhibitors were discovered by scaffold
      hopping strategy. The new derivatives proved to inhibit intracellular
      phosphorylation of hsp27 as well as LPS-induced TNFalpha release in cells. In
      addition, selected derivative 14e also inhibited LPS-induced TNFalpha release in
      vivo.

PMID- 20060295
TI  - Breast cancer survival in different country settings: comparisons between a
      Filipino resident population, Filipino-Americans and Caucasians.
AB  - Various international comparisons of breast cancer survival have shown
      discrepancies which may reflect the impact of ethnicity or health care. Using
      databases from SEER 13 and from the Manila and Rizal Cancer Registries, age
      adjusted five-year absolute and relative survival estimates were computed and
      compared between Filipino-American breast cancer patients, Philippine residents
      and Caucasians in the US. Determinants of survival differences were examined
      using Cox proportional hazards modelling. Age adjusted five-year relative
      survival was almost identical in Filipino-Americans (89.1%) and Caucasians
      (87.7%), but much lower in the Philippine residents (58.4%). Large tumor size,
      lymph node involvement, distant metastasis, and the large proportion of women not
      receiving surgery explained a substantial portion of the excess mortality in
      Philippine residents. The moderate excess risk of Caucasians compared to Filipino
      Americans was explained by age differences. Access to, utilization and
      affordability of cancer care facilities are important for reducing breast cancer
      deaths in developing countries.

PMID- 20060296
TI  - Heritability of the specific cognitive ability of face perception.
AB  - What makes one person socially insightful but mathematically challenged, and
      another musically gifted yet devoid of a sense of direction? Individual
      differences in general cognitive ability are thought to be mediated by
      "generalist genes" that affect many cognitive abilities similarly without
      specific genetic influences on particular cognitive abilities [1]. In contrast,
      we present here evidence for cognitive "specialist genes": monozygotic twins are
      more similar than dizygotic twins in the specific cognitive ability of face
      perception. Each of three measures of face-specific processing was heritable,
      i.e., more correlated in monozygotic than dizygotic twins: face-specific
      recognition ability, the face-inversion effect [2], and the composite-face effect
      [3]. Crucially, this effect is due to the heritability of face processing in
      particular, not to a more general aspect of cognition such as IQ or global
      attention. Thus, individual differences in at least one specific mental talent
      are independently heritable. This finding raises the question of what other
      specific cognitive abilities are independently heritable and may elucidate the
      mechanisms by which heritable disorders like dyslexia and autism can have highly
      uneven cognitive profiles in which some mental processes can be selectively
      impaired while others remain unaffected or even selectively enhanced.

PMID- 20060297
TI  - Chaperone-assisted selective autophagy is essential for muscle maintenance.
AB  - How are biological structures maintained in a cellular environment that
      constantly threatens protein integrity? Here we elucidate proteostasis mechanisms
      affecting the Z disk, a protein assembly essential for actin anchoring in
      striated muscles, which is subjected to mechanical, thermal, and oxidative stress
      during contraction [1]. Based on the characterization of the Drosophila
      melanogaster cochaperone Starvin (Stv), we define a conserved chaperone machinery
      required for Z disk maintenance. Instead of keeping Z disk proteins in a folded
      conformation, this machinery facilitates the degradation of damaged components,
      such as filamin, through chaperone-assisted selective autophagy (CASA). Stv and
      its mammalian ortholog BAG-3 coordinate the activity of Hsc70 and the small heat
      shock protein HspB8 during disposal that is initiated by the chaperone-associated
      ubiquitin ligase CHIP and the autophagic ubiquitin adaptor p62. CASA is thus
      distinct from chaperone-mediated autophagy, previously shown to facilitate the
      ubiquitin-independent, direct translocation of a client across the lysosomal
      membrane [2]. Impaired CASA results in Z disk disintegration and progressive
      muscle weakness in flies, mice, and men. Our findings reveal the importance of
      chaperone-assisted degradation for the preservation of cellular structures and
      identify muscle as a tissue that highly relies on an intact proteostasis network,
      thereby shedding light on diverse myopathies and aging.

PMID- 20060298
TI  - An empirical examination of detrended fluctuation analysis for gait data.
AB  - Stride interval series exhibit statistical persistence, and detrended fluctuation
      analysis (DFA) is a routinely employed technique for describing this behavior.
      However, the implementation of DFA to gait data varies considerably between
      studies. We empirically examine two practical aspects of DFA which significantly
      affect the analysis outcome: the box size range and the stride interval series
      length. We conduct an analysis of their effect using stride intervals from 16
      able-bodied adults, for overground walking, treadmill walking while holding a
      handrail, and treadmill walking without using a handrail. Our goal is to provide
      general guidelines for these two choices, with the aim of standardizing the
      application of DFA and facilitating inter-study comparisons. Based on the results
      of our analysis, we propose the use of box sizes from 16 to N/9, where N is the
      number of stride intervals. Moreover, for differentiating between normal and
      pathological walking with reasonable accuracy, we recommend a minimum of 600
      stride intervals.

PMID- 20060299
TI  - Quorum sensing in natural environments: emerging views from microbial mats.
AB  - Much laboratory-based information exists on quorum sensing, a type of bacterial
      cell-to-cell communication that depends upon exchanges of molecular signals
      between neighboring cells. However, little is known about how this and other
      microbial sensing systems operate in nature. Geochemical and biological
      modifications of signals probably occur in extracellular environments, and these
      could disrupt intended communication if signals are no longer recognized.
      However, as we discuss here, signal alterations might result in other outcomes:
      if a modified signal is able to interact with a different receptor then further
      environmental information can be gained by the receiving cells. We also postulate
      that quorum sensing occurs within cell clusters, where signal dispersion might be
      significantly influenced by extracellular polymers. As a model system to discuss
      these points we use microbial mats - highly-structured biofilm communities living
      under sharply-defined, fluctuating geochemical gradients.

PMID- 20060300
TI  - Encouraging creativity and employability skills in undergraduate microbiologists.
AB  - Key skills such as communication and critical thinking are essential for today's
      microbiology graduate. There are many opportunities within the undergraduate
      curriculum to help students to use, develop and appreciate their own unique set
      of skills. This article describes personal experiences of research-led teaching
      at Manchester Metropolitan University (UK) which have been used successfully to
      encourage creativity and other employability skills in both large and smaller
      classroom settings, and through individual student project work.

PMID- 20060301
TI  - Regulatory crosstalk of the metabolic network.
AB  - The metabolic network has a modular architecture, is robust to perturbations, and
      responds to biological stimuli and environmental conditions. Through monitoring
      by metabolite responsive macromolecules, metabolic pathways interact with the
      transcriptome and proteome. Whereas pathway interconnecting cofactors and
      substrates report on the overall state of the network, specialised intermediates
      measure the activity of individual functional units. Transitions in the network
      affect many of these regulatory metabolites, facilitating the parallel regulation
      of the timing and control of diverse biological processes. The metabolic network
      controls its own balance, chromatin structure and the biosynthesis of molecular
      cofactors; moreover, metabolic shifts are crucial in the response to oxidative
      stress and play a regulatory role in cancer.

PMID- 20060302
TI  - beta-sheet constitution of prion proteins.
AB  - Structural information regarding normal prion protein (PrP(C)) and the scrapie
      isoform (PrP(Sc)) is of vital importance for elucidating the pathogenesis of
      prion diseases (PDs). Despite successful determination of the three-dimensional
      structures of PrP(C), the structural details of PrP(Sc) remain elusive.
      Nevertheless, accumulated evidence indicates that beta-sheets comprise the basic
      building blocks of PrP(Sc). Consensus has been reached about the beta-sheet
      constitution of the N-terminus of PrP, but the constitution of C-terminal beta
      sheets is heavily debated. By evaluating the most recent observations regarding
      the dynamics and structures of PrP, we propose that helix 2 is more likely than
      helices 1 and 3 to participate in beta-sheet formation. This hypothesis also
      provides clues to explaining an intriguing phenomenon in prion biology-the lack
      of PDs in non-mammals.

PMID- 20060303
TI  - Salicylanilide carbamates: antitubercular agents active against multidrug
      resistant Mycobacterium tuberculosis strains.
AB  - A series of 27 salicylanilide-based carbamates was prepared as a part of our
      ongoing search for new antituberculosis drugs. These compounds exhibited very
      good in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii
      and Mycobacterium avium and, in particular, against five multidrug-resistant
      strains, with MIC values between 0.5-2 micromol/L. Moreover, they displayed
      moderate toxicity against intestinal cells with the selectivity index being up to
      96. Furthermore, acid stability and a half-life of 43h at pH 7.4 were shown.
      Thus, these novel salicylanilide derivatives are drug candidates which should be
      seriously consider for further screening.

PMID- 20060304
TI  - beta-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor
      agonists: improvement of solubility by disruption of molecular planarity.
AB  - The physiological role of aryl hydrocarbon receptor (AhR) is not yet fully
      understood, and investigation is hampered by the limited solubility of reported
      AhR ligands in aqueous media. To achieve improved solubility, we focused on our
      previous finding that planarity-disruption of molecules leads to less efficient
      crystal packing and greater aqueous solubility. Here, we describe chemical
      modification of an AhR agonist, beta-naphthoflavone, focusing on planarity
      disruption. As expected, introduction of substituents at the ortho-positions of
      the phenyl group resulted in greater solubility. Among the compounds prepared,
      the fluoro analog showed more potent AhR agonistic activity and greater
      solubility than did beta-naphthoflavone. Our results indicate that this strategy
      to improve aqueous solubility, that is, introduction of substituent(s) that
      disrupt planarity, may be generally applicable to bicyclic molecules.

PMID- 20060305
TI  - Structure-activity relationship of C5-curcuminoids and synthesis of their
      molecular probes thereof.
AB  - A series of novel analogues of 1,5-bis(4-hydroxy-3-methoxyphenyl)-penta-(1E,4E)
      1,4-dien-3-one (C(5)-curcumin), which is a natural analogue of curcumin isolated
      from the rhizomes of Curcuma domestica Val. (Zingiberacea), were synthesized and
      evaluated for their cytotoxicities against human colon cancer cell line HCT-116
      to conclude the SAR of C(5)-curcuminoids for further development of their use in
      cancer chemotherapy: (1) Bis(arylmethylidene)acetone serves as a promising
      skeleton for eliciting cytotoxicity. (2) The 3-oxo-1,4-pentadiene structure is
      essential for eliciting cytotoxicity. (3) As for the extent of the aromatic
      substituents, hexasubstituted compounds exhibit strong activities, in which 3,4,5
      hexasubstitution results in the highest potency. (5) The symmetry between two
      aryl rings is not an essential requirement for bis(arylmethylidene)acetones to
      elicit cytotoxicity. (6) para-Positions allows the installation of additional
      functional groups for use as molecular probes. By taking advantage of the SAR
      diagram, we have elaborated several advanced derivatives having GI(50) of single
      digit micromolar potencies that will function as molecular probes to target
      and/or report key biomolecules interacting with curcumin and C(5)-curcumin.

PMID- 20060306
TI  - Novel amidino substituted 2-phenylbenzothiazoles: synthesis, antitumor evaluation
      in vitro and acute toxicity testing in vivo.
AB  - The efficient synthesis of new bis-substituted nitro-amidino, amino-amidino (10a,
      10b-13a, 13b) and previously prepared diamidino 2-phenyl-benzothiazoles (9a, 9b)
      is described. The compounds 11a and 11b were prepared by recently developed
      methodology of the key precursors in zwitterionic form 8a and 8b with 4
      nitrobenzoylchloride in a very good yield (70%). All compounds except diamidino
      substituted 2-phenylbenzothiazole 9a show exceptionally prominent tumor cell
      growth inhibitory activity and cytotoxicity, whereby the special selectivity of
      amino-amidine 2-phenylbenzothiazole 12a towards MCF-7 and H 460 cells makes this
      compound a prospective lead compound that should be further evaluated in animal
      models. All in vivo tested compounds (12a, 12b, 13a and 13b) are absorbed from
      mice gastrointestinal system. LD(50) are between 67.33 and 696.2mg/kg body weight
      (OECD/EPA toxicity categories 2-3).

PMID- 20060307
TI  - Diagnostic assessment to estimate and minimize neutron dose rates received by
      occupationally exposed individuals at cyclotron facilities.
AB  - Since 2003, radiopharmaceuticals for medical diagnostic purposes have been
      produced at the Instituto de Engenharia Nuclear, in Brazil, using two cyclotron
      accelerators - CV-28 and RDS111. As a result of the ever increasing production, a
      diagnostic assessment to reduce neutron dose rates received by occupationally
      exposed individuals during irradiation processes has been developed. The purpose
      of this work is to present this assessment, which is currently being applied to
      both the Fluorine and Iodine targets of CV-28 and RDS111 cyclotron accelerators.

PMID- 20060308
TI  - Absolute 108Agm characterization based on gamma-gamma coincident detection by two
      NaI(Tl) detectors.
AB  - A two-dimensional analysis of three coincident gamma-rays in (108)Ag(m) decay,
      detected by two NaI(Tl) scintillation detectors, allows a direct measurement of
      the source activity. A modification of the Eldridge-Crowther formulas derived
      originally for (125)I was done recently for the case of two coincident gamma-rays
      in (60)Co decay (Volkovitsky and Naudus, 2009). A similar approach is applied to
      a more complicated case of three coincident gamma-rays in the (108)Ag(m) decay.
      The large number of experimental quantities, measured both in coincidence and
      anticoincidence modes, allows the determination of both detector efficiencies for
      all three gamma-ray photopeaks and to find the source activity. Results are
      compared with measurements of the activity of the same source with HPGe
      detectors.

PMID- 20060309
TI  - Investigation into the standardization of 99Tc.
AB  - The standardization of (99)Tc by several primary methods was investigated. This
      was performed to support a new (99)Tc transfer standard that has been developed
      and will be disseminated by the National Institute of Standards and Technology
      (NIST) as Standard Reference Material SRM 4288B. The standardization for the
      (99)Tc content of the solution was based on 4pibeta liquid scintillation (LS)
      measurements with (3)H-standard efficiency tracing (CIEMAT/NIST method).
      Confirmatory determinations were performed by 4pibeta(LS)-gamma(NaI) live-timed
      anti-coincidence (LTAC) counting and an LS-based 4pibeta triple-to-double
      coincidence ratio (TDCR) method.

PMID- 20060310
TI  - Distribution of resveratrol and stilbene synthase in young grape plants (Vitis
      vinifera L. cv. Cabernet Sauvignon) and the effect of UV-C on its accumulation.
AB  - Current research indicated that the resveratrol was mainly accumulated in the
      skin of grape berry, however, little is yet known about the distribution of
      resveratrol, as well as the regulation mechanism at protein level and the
      localization of stilbene synthase (malonyl-CoA:4-coumaroyl-CoA
      malonyltransferase; EC 2.3.1.95; STS), a key enzyme of resveratrol biosynthesis,
      in young grape plants (Vitis vinifera L. cv. Cabernet Sauvignon). Resveratrol,
      whose constitutive level ranged from 0.2 mg kg(-1) FW to 16.5 mg kg(-1) FW, could
      be detected in stem, axillary bud, shoot tip, petiole, root and leaf of grape
      plants. Among them, stem phloems presented the most abundant of resveratrol, and
      the leaves presented the lowest. Interestingly, the level of STS mRNA and protein
      were highest in grape leaves. And the analysis of immunohistochemical showed the
      tissue-specific distribution of STS in different organs, presenting the similar
      results compared with the amount of protein. And the subcellular localization
      revealed that the cell wall in different tissues processed the most golden
      particles representing STS. Subjecting to UV-C irradiation, resveratrol and STS
      were both intensely stimulated in grape leaves, with the similar response
      pattern. Results above indicated that distribution of resveratrol and STS in
      grape was organ-specific and tissue-specific. And the accumulation of resveratrol
      induced by UV-C was regulated by transcriptional and translational level of STS.

PMID- 20060311
TI  - Endovascular repair of an intra-thoracic ruptured aneurysm of left subclavian
      artery in a patient with a right-sided aortic arch with aberrant left subclavian
      artery.

PMID- 20060312
TI  - Mitochondria-targeting properties and photodynamic activities of porphyrin
      derivatives bearing cationic pendant.
AB  - Four meso-tetraphenylporphyrin derivatives bearing either triphenylphosphonium
      ion-(P1 and P2) or triethylammonium ion-(P3 and P4) terminated alkoxy group at
      either para-(P1 and P3) or meta-(P2 and P4) position of one meso-phenyl group
      were designed and synthesized. P1-P4 show similar absorption and fluorescence
      emission spectra and (1)O(2) quantum yields. The more lipophilic nature of
      triphenylphosphonium ion over triethylammonium ion renders P1 and P2 higher
      octanol/water partition coefficients than P3 and P4. Confocal fluorescence
      microscopy proved that P1-P4 are all mitochondria-targeting. MTT assay showed
      that P1-P4 presented significant phototoxicity at the concentrations that dark
      toxicity is negligible towards human breast cancer cell line MCF-7 cells,
      displaying their application potential in PDT.

PMID- 20060313
TI  - Identifying an accurate pre-screening tool in geriatric oncology.
AB  - The use of comprehensive geriatric assessment (CGA) in cancer patients older than
      70 is recommended. Three pre-screening instruments have been proposed: the
      abbreviated comprehensive geriatric assessment (aCGA), the Vulnerable Elders
      Survey (VES-13), and the Groningen frailty index (GFI). The objective of the
      study was to identify the most efficient pre-screening tool that accurately
      determines individuals who may benefit from the entire CGA. A total of 113
      elderly cancer patients were assessed by means of the aCGA, VES-13, GFI and the
      full CGA. The sensitivity, specificity of the three instruments was calculated,
      using the results from the entire CGA as the gold standard for the GFI and the
      VES-13. The aCGA was assessed whether each sub-component reliably predicts
      impairment on each sub-component of the full CGA. The majority of the
      participants were defined as being at risk of vulnerability: 68.14% had two or
      more impairments of the CGA or were cognitively impaired. The physical and
      disability questions are useful, but all other screening instruments miss too
      many cases.

PMID- 20060314
TI  - Gonadotropin inhibitory hormone function in mammals.
AB  - Reproductive function depends on the stimulatory action of gonadotropin-releasing
      hormone (GnRH), secreted by the brain. Original work in birds identified and
      isolated a peptide that inhibits gonadotropin release, named gonadotropin
      inhibitory hormone (GnIH). There is no evidence for a similar factor operant in
      mammals. This mammalian orthologue of GnIH has been named RFamide-related peptide
      (RFRP), and negatively regulates GnRH function and gonadotropin secretion. In
      particular, mammalian GnIH inhibits the function of GnRH cells and acts at the
      level of gonadotropes. It appears to play a major role in seasonal regulation of
      reproduction and also to be involved in regulation of stress and food intake.

PMID- 20060315
TI  - High mass selectivity for top-down proteomics by application of SWIFT technology.
AB  - Stored waveform inverse Fourier transform (SWIFT) technology has been implemented
      on a commercial Fourier transform ICR mass spectrometer. Complex
      ejection/isolation waveforms can be generated on an arbitrary waveform generator
      (AWG) and applied to the instrument by use of a high speed analog switch. High
      mass selectivity and subsequent electron capture dissociation (ECD) of the SWIFT
      isolated ions has been demonstrated with analysis of intact Bovine histone H4. A
      mass selectivity about 0.1 m/z unit for isolation of the 18+ charge state ions
      was achieved. Adaptation of SWIFT on the commercial instrument provides an
      enhanced capability for characterizing intact proteins by top-down analysis.

PMID- 20060316
TI  - Classical trajectories and RRKM modeling of collisional excitation and
      dissociation of benzylammonium and tert-butyl benzylammonium ions in a quadrupole
      hexapole-quadrupole tandem mass spectrometer.
AB  - Collision-induced dissociation of the benzylammonium and the 4-tert-butyl
      benzylammonium ions was studied experimentally in an electrospray ionization
      quadrupole-hexapole-quadrupole tandem mass spectrometer. Ion fragmentation
      efficiencies were determined as functions of the kinetic energy of ions and the
      collider gas (argon) pressure. A theoretical Monte Carlo model of ion collisional
      excitation, scattering, and decomposition was developed. The model includes
      simulation of the trajectories of the parent and the product ions flight through
      the hexapole collision cell, quasiclassical trajectory modeling of collisional
      activation and scattering of ions, and Rice-Ramsperger-Kassel-Marcus (RRKM)
      modeling of the parent ion decomposition. The results of modeling demonstrate a
      general agreement between calculations and experiment. Calculated values of ion
      fragmentation efficiency are sensitive to initial vibrational excitation of ions,
      scattering of product ions from the collision cell, and distribution of initial
      ion velocities orthogonal to the axis of the collision cell. Three critical
      parameters of the model were adjusted to reproduce the experimental data on the
      dissociation of the benzylammonium ion: reaction enthalpy and initial internal
      and translational temperatures of the ions. Subsequent application of the model
      to decomposition of the t-butyl benzylammonium ion required adjustment of the
      internal ion temperature only. Energy distribution functions obtained in modeling
      depend on the average numbers of collisions between the ion and the atoms of the
      collider gas and, in general, have non-Boltzmann shapes.

PMID- 20060317
TI  - Repetitive eccentric muscle contractions increase torque unsteadiness in the
      human triceps brachii.
AB  - Torque steadiness and low-frequency fatigue (LFF) were examined in the human
      triceps brachii after concentric or eccentric fatigue protocols. Healthy young
      males (n=17) performed either concentric or eccentric elbow extensor contractions
      until the eccentric maximal voluntary torque decreased to 75% of pre-fatigue for
      both (concentric and eccentric) protocols. The number of concentric contractions
      was greater than the number of eccentric contractions needed to induce the same
      25% decrease in eccentric MVC torque (52.2+/-2.9 vs. 41.5+/-2.1 for the
      concentric and eccentric protocols, respectively, p<.01). The extent of
      peripheral fatigue was approximately 12% greater after the concentric compared to
      the eccentric protocol (twitch amplitude), whereas LFF (increase in double pulse
      torque/single pulse torque), was similar across protocols. Steadiness, or the
      ability for a subject to hold a submaximal isometric contraction, was
      approximately 20 % more impaired during the Ecc protocol (p=.052). Similarly, the
      EMG activity required to hold the torque steady was nearly 20% greater after the
      eccentric compared to concentric protocol. These findings support that task
      dependent eccentric contractions preferentially alter CNS control during a
      precision based steadiness task.

PMID- 20060318
TI  - Postural reactions following forward platform perturbation in young, middle-age,
      and old adults.
AB  - The aim of the study was to examine how individuals of different ages react to
      forward balance perturbations. Thirty-six volunteers, divided into four groups
      [young (YA), middle-age (MA(40) and MA(50)), and old (OA) adults], stood on a
      platform that was either kept stationary, moved backward, or moved forward. EMG
      onset, EMG time-to-peak, iEMG, and agonist-antagonist co-activation, as well as
      cumulative angular excursion, maximum center of mass (CM) backward displacement,
      and CM time-to-reversal were assessed after forward translations. Postural
      synergies were assessed using principal component analysis (PCA). The results
      showed that OA activated their muscles later than YA [TA=25 ms, RF=17 ms] and OA
      and MA(50) reached the peak of activation later than YA [MA(50):TA=23 ms, RF=32
      ms, OA:TA=28 ms, RF=21 ms]. Moreover, OA kept a higher level of activation longer
      than all younger groups. No differences among groups were observed in co
      activation, kinematic, and PCA variables. We conclude that changes in temporal
      EMG patterns can be seen in the fifth decade. However, such changes have no
      effect on the CM horizontal displacement and CM time-to-reversal after
      perturbation, which cannot be justified by the use of different postural
      synergies, suggesting that temporal aspects of muscle activation could play a
      minor role in controlling excessive CM displacements after perturbations.

PMID- 20060320
TI  - Acute lung injury after thoracic surgery.
AB  - In this review, the authors discussed criteria for diagnosing ALI; incidence,
      etiology, preoperative risk factors, intraoperative management, risk-reduction
      strategies, treatment, and prognosis. The anesthesiologist needs to maintain an
      index of suspicion for ALI in the perioperative period of thoracic surgery,
      particularly after lung resection on the right side. Acute hypoxemia, imaging
      analysis for diffuse infiltrates, and detecting a noncardiogenic origin for
      pulmonary edema are important hallmarks of acute lung injury. Conservative
      intraoperative fluid administration of neutral to slightly negative fluid balance
      over the postoperative first week can reduce the number of ventilator days. Fluid
      management may be optimized with the assistance of new imaging techniques, and
      the anesthesiologist should monitor for transfusion-related lung injuries. Small
      tidal volumes of 6 mL/kg and low plateau pressures of < or =30 cmH2O may reduce
      organ and systemic failure. PEEP may improve oxygenation and increases organ
      failure-free days but has not shown a mortality benefit. The optimal mode of
      ventilation has not been shown in perioperative studies. Permissive hypercapnia
      may be needed in order to reduce lung injury from positive-pressure ventilation.
      NO is not recommended as a treatment. Strategies such as bronchodilation, smoking
      cessation, steroids, and recruitment maneuvers are unproven to benefit mortality
      although symptomatically they often have been shown to help ALI patients. Further
      studies to isolate biomarkers active in the acute setting of lung injury and
      pharmacologic agents to inhibit inflammatory intermediates may help improve
      management of this complex disease.

PMID- 20060319
TI  - Independent and joint associations of nutritional status indicators with
      mortality risk among chronic hemodialysis patients in the Dialysis Outcomes and
      Practice Patterns Study (DOPPS).
AB  - OBJECTIVE: To consider the Kidney Disease Outcomes Quality Initiative
      recommendation of using multiple nutritional measurements for patients on
      maintenance dialysis, we explored data for independent and joint associations of
      nutritional indicators with mortality risk among maintenance hemodialysis
      patients treated in 12 countries. SETTING: Dialysis units in seven European
      countries, the United States, Canada, Australia, New Zealand, and Japan. MAIN
      OUTCOME: Mortality risk. METHODS: We conducted a prospective cohort study of
      40,950 patients from phases I to III of the Dialysis Outcomes and Practice
      Patterns Study (1996-2008). Independent and joint effects (interactions) of
      nutritional indicators (serum creatinine, serum albumin, normalized protein
      catabolic rate, body mass index [BMI]) on mortality risk were assessed by Cox
      regression with adjustments for demographics, years on dialysis, and
      comorbidities. RESULTS: Important variations in nutritional indicators were seen
      by country and patient characteristics. Poorer nutritional status assessed by
      each indicator was independently associated with higher mortality risk across
      regions. Significant multiplicative interactions (each p < or = 0.01) between
      indicators were also observed. For example, by using patients with serum
      creatinine 7.5-10.5 mg/dL and BMI 21-25 kg/m(2) as referent, BMI <21 kg/m(2) was
      associated with lower mortality risk among patients with creatinine >10.5 mg/dL
      (relative risk = 0.68) but with higher mortality risk among those with creatinine
      <7.5 mg/dL (relative risk = 1.38). The association of lower albumin concentration
      with higher mortality risk was stronger for patients with lower BMI or lower
      creatinine. CONCLUSION: The joint effects of nutritional indicators on mortality
      indicate the need to use multiple measurements when assessing the nutritional
      status of hemodialysis patients.

PMID- 20060321
TI  - Ideal methodology to assess systemic blood pressure in patients with continuous
      flow left ventricular assist devices.

PMID- 20060322
TI  - Combined treatment with chemokine receptor 5 blocker and cyclosporine induces
      prolonged graft survival in a mouse model of cardiac transplantation.
AB  - BACKGROUND: Inhibition of chemokine receptor 5 (CCR5), a chemokine receptor
      expressed on activated T cells, is efficacious in modulating inflammation and
      immunity as well as in patients with human immunodeficiency virus infection. This
      study examined the effect and mechanism of CCR5 blockade in combination with
      cyclosporine in prolonging cardiac allograft survival in mice. METHODS: Hearts
      from BALB/c mice were transplanted into C57BL/10 recipients. They were
      administrated with anti-CCR5 antibody (Ab) or control Ab and cyclosporine or
      phosphate-buffered (PBS) saline, respectively. To investigate the role of
      regulatory cells, naive mice (secondary recipients) underwent adoptive transfer
      of splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients and cardiac
      allograft transplantation. RESULTS: Compared with recipients treated with control
      Ab plus PBS, allografts treated with anti-CCR5 Ab and cyclosporine showed
      significantly prolonged survival (p < 0.001), markedly decreased CD4+ and CD8+ T
      cells (p < 0.005), and increased frequency of CD4+CD25+Foxp3+ regulatory cells
      (23.98% +/- 1.55% vs 6.30% +/- 0.57%, p < 0.005). Adoptive transfer of CD4+CD25+
      splenocytes from anti-CCR5 Ab plus cyclosporine-treated recipients induced
      significantly prolonged survival in secondary recipients (p < 0.01 vs adoptive
      transfer from naive mice and recipients depleted of CD25+ cells). CONCLUSIONS:
      CCR5 blockade combined with cyclosporine is effective in protecting the cardiac
      allograft in a robust murine model. This effect is partly mediated by regulatory
      cell recruitment and control of effector cell infiltration.

PMID- 20060323
TI  - Asymptomatic infection with novel influenza A/H1N1 virus in a heart transplant
      recipient.
AB  - The spectrum of manifestations and management of the novel influenza A/H1N1 virus
      in transplanted patients is currently of major concern. Asymptomatic infections
      are less common yet important for spreading of the virus and thus affect
      containment measures. To our knowledge, there are no reports of asymptomatic
      infections with influenza A/H1N1 in immunosuppressed patients. We present the
      first case of a young heart transplant recipient who remained asymptomatic
      despite positive polymerase chain reaction (PCR) after exposure to individuals
      with influenza A/H1N1.

PMID- 20060324
TI  - Primary cardiac tumors: a clinicopathologic evaluation of four cases.
AB  - INTRODUCTION: We report the clinical, pathological, and immunohistochemical
      features of four primary malignant cardiac tumors identified at the Department of
      Pathology, Rigshospitalet, Denmark. A panel of immunohistochemical markers for
      classification is proposed. METHODS: Between 2000 and 2008, four patients with
      malignant cardiac tumors were treated at our hospital. We retrospectively
      reviewed the medical records and evaluated the patient characteristics and
      treatment. RESULTS: Three patients presented with severe dyspnea; one patient
      presented with chest pain. Transthoracic echocardiography demonstrated, in all
      four cases, abnormal masses in the atria. The cases were, based on morphological
      features and immunoprofile, classified as myogenic sarcoma (two cases),
      undifferentiated pleomorphic sarcoma, and leiomyosarcoma. Three of the patients
      received orthotopic heart transplantation. One patient survived 6.5 years after
      the diagnosis, and two patients are still alive 2 and 3 years after being
      diagnosed, respectively. CONCLUSIONS: All four cases were sarcomas. A limited
      number of immunohistochemical markers can be used in order to define a specific
      line of differentiation. In this small study, three of the patients were offered
      orthotopic heart transplantation, and the survival times were generally longer
      than in most series.

PMID- 20060325
TI  - Protein kinase G activity prevents pathological-level nitric oxide-induced
      apoptosis and promotes DNA synthesis/cell proliferation in vascular smooth muscle
      cells.
AB  - BACKGROUND: Protein kinase G (PKG), a recognized downstream mediator of nitric
      oxide, is a key regulator of cardiovascular physiology and pathology. High-level
      stimulation of cyclic guanosine monophosphate/PKG signaling using high
      concentrations of nitric oxide donors, mimicking pathological conditions, induces
      apoptosis in vascular smooth muscle cells. In contrast, we have found that PKG at
      basal and moderately elevated activity prevents both spontaneous and toxin
      induced apoptosis in many other cells. We hypothesized that PKG's apoptosis
      regulatory role in vascular smooth muscle cells depends on PKG activation levels
      [low/basal-level activation prevents apoptosis, whereas high-level activation
      (hyperactivation) causes apoptosis]. Furthermore, we hypothesized that, although
      PKG hyperactivation inhibits vascular smooth muscle cell proliferation
      (potentially causing anti-atherogenic effects), basal PKG activity may promote
      vascular smooth muscle cell proliferation/atherogenesis. METHODS: Involvement of
      PKG in apoptosis and proliferation was determined in unpassaged vascular smooth
      muscle cells from mouse aorta. Western blot analysis was used to determine PKG
      expression, and activators/inhibitors of PKG activity were used to determine
      involvement in apoptosis (Hoechst staining and DNA-fragmentation ELISAs) and
      proliferation (cell count, MTT assay, and BrdU incorporation). RESULTS: Both PKG
      Ialpha and PKG-Ibeta isoforms were expressed. Lower-level stimulation of PKG
      using the nitric oxide donor S-nitroso-acetylpenacillamine (10, 50 MUM)
      significantly (P<.05) lowered spontaneous apoptosis, whereas S-nitroso
      acetylpenacillamine at higher concentrations (500, 1000 MUM) elevated apoptosis.
      Twenty-four-hour pretreatment with atrial natriuretic peptide, a PKG activator,
      completely prevented high-concentration, nitric oxide-induced apoptosis.
      Inhibition of basal PKG activity using highly selective PKG inhibitors, DT-2 and
      DT-3, significantly (P<.001) increased apoptosis and inhibited DNA
      synthesis/proliferation. CONCLUSION: The data suggest that basal/moderately
      elevated PKG activity protects against high/pathological-level nitric oxide
      induced apoptosis and promotes DNA synthesis/proliferation in vascular smooth
      muscle cells, potentially important for atherogenesis.

PMID- 20060326
TI  - Molecular basis and diagnosis of both inherited and acquired cardiovascular
      diseases: introduction.

PMID- 20060327
TI  - Adult congenital heart disease--challenges and opportunities for pathologists.
AB  - Adults living with congenital heart disease (CHD) are numerous, at a prevalence
      of about four per 1000 population. Many of these patients are now over the age of
      40 years. Typically, these adult CHD patients have had or require one or more
      invasive interventions, and thus most of them have modified anatomy and
      physiology. Despite professional education programs aimed at cardiologists,
      surgeons, radiologists, pathologists, and others to improve awareness of "grown
      up kids" with CHD, there is still a paucity of caregivers who feel competent with
      these patients. An appreciation by pathologists of the main types of clinically
      modified congenital lesions seen in adult patients with CHD is of great
      importance in terms of helping clinicians understand why patients ultimately die
      (often prematurely) and in explaining the dysfunction and deterioration of
      biomaterials and devices required for care. Among the most common lesions
      observed in adults, atrial and ventricular septal defects, patent ductus
      arteriosus, coarctation of the aorta, tetralogy of Fallot, pulmonary atresia,
      transposition of the great arteries, single ventricle and Fontan circulation, and
      Ebstein anomaly are especially worthy of mention. General considerations needing
      attention for patients with adult CHD include tracking and follow-up, pregnancy
      guidance and counseling, noncardiac surgery risks, thrombosis, pulmonary
      hypertension, endocarditis risk, and arrhythmia management. Pathologists may
      contribute to supporting the families who are affected. As well, many of the
      adult patients with CHD now live long enough to develop atherosclerosis and all
      of its attendant morbidities and pathologies.

PMID- 20060328
TI  - Immunohistochemical evaluation of three nitric oxide synthase isoforms in human
      saphenous vein exposed to different degrees of distension pressures.
AB  - The effect of short duration and different degrees of distension pressures was
      investigated by means of immunohistochemistry of the three nitric oxide synthase
      isoforms in the human saphenous vein conventionally harvested from 20 patients
      submitted to coronary artery bypass graft. The human saphenous vein distal
      portion was divided into four segments, each one allocated to a different group.
      In Group I (control group), the human saphenous vein segment was not exposed to
      distension pressure. In Groups II, III, and IV, the human saphenous vein segment
      was exposed to 100, 200, and 300 mmHg of distension pressure, respectively. The
      distension pressures were applied and maintained with Krebs solution for 15 s.
      The human saphenous vein of the control group presented endothelial nitric oxide
      synthase and neuronal nitric oxide synthase in both endothelial and smooth muscle
      cells, while the inducible nitric oxide synthase appeared predominantly in the
      medial layer. Neither 100 nor 200 mmHg of pressurization affected the
      immunostaining of any nitric oxide synthase isoform. However, the human saphenous
      vein segments exposed to 300 mmHg of distension pressure showed a reduction in
      endothelial nitric oxide synthase content in the endothelium, but not in the
      tunica media. This lower endothelial nitric oxide synthase immunostaining in the
      intimal cells was associated with endothelial denudation. Therefore, we conclude
      that care should be taken when handling the human saphenous vein since just a few
      seconds of distension pressure above the normal systemic pressure can be
      sufficient to disrupt the endothelium reducing the amount of endothelial nitric
      oxide synthase and impairing the graft quality.

PMID- 20060329
TI  - The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the
      interleukin-1 receptor pathway and mTOR kinase activation.
AB  - Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17
      (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of
      IL-1 receptor and Toll-like receptor signaling, was induced during Th17 cell
      lineage commitment and governed Th17 cell differentiation and expansion through
      its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells
      resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte
      glycoprotein (MOG(35-55)) peptide immunization. Recombinant IL-1 promoted a
      marked increase in the proliferation of SIGIRR-deficient T cells under an in
      vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1
      induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells
      compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in
      mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our
      results demonstrate an important mechanism by which SIGIRR controls Th17 cell
      expansion and effector function through the IL-1-induced mTOR signaling pathway.

PMID- 20060331
TI  - Prostate-specific antigen: an evolving role in diagnosis, monitoring, and
      treatment evaluation in prostate cancer.
AB  - Prostate specific antigen (PSA) was introduced as a prostate cancer screening
      tool more than 20 years ago. However, there is continuing debate regarding its
      utility in screening for prostate cancer. Mass screening is costly, may result in
      the diagnosis and treatment of prostate cancers that never become clinically
      significant, and the evidence of a subsequent reduction in mortality is
      inconclusive. In addition to its role in screening, PSA is also used to monitor
      the progression of the disease, both localized and metastatic. Although the
      evidence is contradictory, PSA is still an important tool for monitoring patient
      progression following treatment of definitive localized prostate cancer. However,
      its use in monitoring castrate-resistant prostate cancer (CRPC) is more
      controversial, particularly in the context of novel targeted treatments, which
      may have little impact on PSA levels. These issues highlight the urgent need to
      identify prostate cancer biomarkers that will improve early disease detection,
      increase accuracy of diagnosis, determine the aggressiveness of disease, and
      monitor treatment efficacy, particularly in late-stage disease. This review
      discusses the key issues associated with the use of PSA as an early screening
      tool for prostate cancer, as a prognostic marker to measure disease progression
      in both early- and late-stage prostate cancer, and as a surrogate endpoint in
      clinical trials with new agents.

PMID- 20060330
TI  - The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating
      the expression of transcription factors T-bet and Eomesodermin.
AB  - The mechanisms underpinning integration of instructions that program naive CD8+ T
      cells for effector and/or memory differentiation are not well understood. Herein,
      we demonstrate that interleukin-12 (IL-12) enhanced and sustained antigen and
      costimulatory molecule (B7.1)-induced mTOR kinase activity in naive CD8+ (OT-I) T
      cells via phosphoinositide 3-kinase and STAT4 transcription factor pathways.
      Blocking mTOR activity by rapamycin reversed IL-12-induced effector functions
      because of loss of persistent expression of the transcription factor T-bet.
      Rapamycin treatment of IL-12-conditioned OT-I cells promoted persistent
      Eomesodermin expression and produced memory cell precursors that demonstrated
      enhanced sustenance and antigen-recall responses upon adoptive transfer. The
      memory cell precursors showed greater tumor efficacy than IL-12-conditioned
      effector OT-I cells. These results identify mTOR as the central regulator of
      transcriptional programs that determine effector and/or memory cell fates in CD8+
      T cells. Targeting mTOR activity offers new opportunities to regulate CD8+ T cell
      mediated immunity.

PMID- 20060332
TI  - Squamous cell carcinoma of the penis: predicting nodal metastases by histologic
      grade, pattern of invasion and clinical examination.
AB  - With a diagnosis of squamous cell carcinoma of the penis, there is still a
      significant need to define the tumor criteria that allow the disease to be
      stratified according to the risk of developing lymph node metastases. The
      histopathology of the primary tumor in 72 consecutive patients with resected
      squamous cell carcinoma of the penis was reviewed for this study. Tumor tissue
      was reviewed for (1) histologic grade, (2) invasion pattern, (3) tumor stage, (4)
      proportion of poorly differentiated tumor cells, (5) invasion depth, (6)
      proportion of tumor necrosis, (7) angioinvasion, (8) histologic classification,
      (9) number of lesions, (10) growth pattern, (11) number of mitoses, (12) degree
      of keratinization, and (13) clinical groin status. It was found that the presence
      of inguinal lymph node metastases correlated in descending order of frequency
      with grade G2/G3, clinically positive groin status, reticular invasion, stage
      pT2/T3, >50% poorly differentiated tumor cells, depth of invasion, and comedolike
      tumor necrosis. These results revealed that the risk of inguinal lymph node
      metastasis in penile carcinoma can be predicted on the basis of 3 major factors:
      histologic grade, pattern of invasion, and clinical groin status.

PMID- 20060333
TI  - Comment on "endovascular treatment of profunda femoris artery obstructive
      disease: nonsense or useful tool in selected cases?".

PMID- 20060334
TI  - Thrombolysis or immediate surgery for thrombosed popliteal aneurysms?

PMID- 20060335
TI  - Comment on "Long-term results using catheter-directed thrombolysis in 103 lower
      limbs with acute iliofemoral venous thrombosis".

PMID- 20060336
TI  - Development of a novel bone grafting material using autogenous teeth.
AB  - We developed a novel bone grafting material that incorporates autogenous teeth
      (AutoBT), and provided the basis for its clinical application. AutoBT contains
      organic and inorganic mineral components and is prepared from autogenous grafting
      material, thus eliminating the risk of an immune reaction that may lead to
      rejection. AutoBT was used at the time of implant placement, simultaneously with
      osteoinduction surgery, and excellent bony healing by osteoinduction and
      osteoconduction was confirmed.

PMID- 20060337
TI  - An evaluation of microbiologic contamination on a phosphor plate system: is
      weekly gas sterilization enough?
AB  - OBJECTIVE: This study was performed to determine: 1) the rate and source of
      microbiologic contamination of photostimulable phosphor plates (PSP) in a
      predoctoral clinic; and 2) whether a combination of weekly gas sterilization and
      barrier protocols can prevent contamination of PSP plates. METHODS: Fifty plates
      in clinical use and 25 gas-sterilized control plates were selected for
      examination. The PSP plates were pressed onto blood agar medium and incubated at
      37 degrees C. The number, size, distribution, and variety of resulting colonies
      were noted. To test whether these bacteria could have come from oral sources, 17
      colonies were selected for culture on Mitis-Salivarius (M-S) agar. Those colonies
      that grew on the M-S agar were Gram stained. RESULTS: Twenty-eight test plates
      (56%) exhibited growth of bacterial colonies on blood agar. Seventeen of those
      bacterial colonies were selected for growth on M-S agar, and 13 (76.47%) showed
      growth, 69% of them gram positive. CONCLUSION: Our results indicate reinforcing
      standard precautions of infection control for intraoral radiography, and that gas
      sterilization of plates after each day's clinical use is a potential solution.

PMID- 20060338
TI  - Susceptibility of Candida albicans to photodynamic therapy in a murine model of
      oral candidosis.
AB  - OBJECTIVE: In vivo studies of antimicrobial PDT in animal models of oral
      candidosis are scarce and the association of porphyrin and LED light has not been
      evaluated for in vivo photoinactivation of Candida. In this study the
      effectiveness of photodynamic therapy (PDT) on the inactivation of Candida
      albicans in vivo was evaluated. STUDY DESIGN: Seventy-one 6-week-old female Swiss
      mice were immunosuppressed, provided tetracycline to their drinking water, then
      orally swabbed with a suspension of C. albicans (10(7) CFU/mL). Four days after
      oral inoculation, PDT was performed on the dorsum of the tongue after topical
      administration of Photogem at 400, 500, or 1000 mg/L and followed 30 minutes
      later by illumination with LED light (305 J/cm(2)) at 455 or 630 nm (n = 5 each).
      After swabbing to recover yeast from the tongue, the number of surviving yeast
      cells was determined (CFU/mL) and analyzed by ANOVA and Holm-Sidak tests (P <
      .05). Animals were humanely killed, and the tongues surgically removed and
      processed for histological evaluation of presence of yeast and inflammatory
      reaction. RESULTS: PDT resulted in a significant reduction in C. albicans
      recovered from the tongue (P < .001) when compared with mice from the positive
      control group. There was no difference between the concentrations of Photogem and
      LED light wavelengths used. Histological evaluation of the tongue revealed that
      PDT causes no significant adverse effects to the local mucosa. CONCLUSION: PDT
      promoted significant reduction in the viability of C. albicans biofilm without
      harming the tongue tissue.

PMID- 20060339
TI  - Jaw bone changes in rats after treatment with zoledronate and pamidronate.
AB  - OBJECTIVE: The aim of this study was to histopathologically evaluate the effects
      of pamidronate and zoledronate on the mandible in an animal model. STUDY DESIGN:
      Sixty female Sprague-Dawley rats were used in this study. Animals were divided
      into 6 groups (10 per group): control-1 (C1), injected with saline solution for 6
      weeks; zoledronate-1 (ZA1), injected with zoledronate for 6 weeks; pamidronate-1
      (PA1), injected with pamidronate for 6 weeks; control-2 (C2), injected with
      saline solution for 8 weeks; zoledronate-2 (ZA2), injected with zoledronate for 8
      weeks; and pamidronate-2 (PA2), injected with pamidronate for 8 weeks. No dental
      procedures were performed on the animals. Rats were killed 2 days after the end
      of drug therapy, and the posterior and anterior mandible and femur of each rat
      were evaluated histopathologically. RESULTS: Histological examination revealed
      inflammation limited to the posterior mandible of the ZA2 and PA2 groups; the
      anterior mandible and femur were not affected. Soft tissue necrosis was evident
      in one rat in the ZA2 group. CONCLUSION: Specific, bisphosphonate-associated
      inflammatory bony and soft tissue changes were observed in the mandible,
      suggesting that these drugs may set the stage for altered healing associated with
      the development of bisphosphonate-related osteonecrosis of the jaw.

PMID- 20060341
TI  - Abdominal fat harvest technique and its uses in maxillofacial surgery.
AB  - Abdominal fat harvest and augmentation to the maxillofacial region is a
      relatively inexpensive, safe, and readily available procedure. The use of
      abdominal fat free transfer has been well documented for cosmetic, trauma, and
      temporomandibular joint reconstruction. Fat is the closest we have to an ideal
      filler, it is readily available and inexpensive, it is autologous and therefore
      lacks a host immune response, it is safe and noncarcinogenic, and it is easily
      acquired with a minimally invasive procedure. Abdominal fat donor site is the
      most commonly used owing to ease of access and availability of fat stores.
      Complications are rare and easily managed in the office. Free abdominal fat
      harvest is a predictable surgical technique that allows the maxillofacial surgeon
      access to autologous graft material that is ideal for multiple facial procedures.

PMID- 20060340
TI  - Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel
      membrane in rabbit calvarial defects.
AB  - OBJECTIVES: The aims of this study were to test whether or not the application of
      an in situ-formed synthetic polyethylene glycol hydrogel (PEG) used as a
      biodegradable membrane for guided bone regeneration with a variety of graft
      materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result
      in enhanced bone regeneration, and to observe the histologic and
      histomorphometric aspects of bone healing of the calvarial defects with and
      without a PEG membrane. STUDY DESIGN: Thirty adult, skeletally mature, male New
      Zealand white rabbits were randomly divided into 3 groups of 10 animals each.
      Bilateral 15-mm-diameter critical-size defects were created in the parietal bones
      of each animal. Group 1 served as a control with unfilled bilateral calvarial
      defects, group 2 had bilateral calvarial defects filled with morcelized
      autogenous calvarial bone, and group 3 had bilateral calvarial defects filled
      with a biphasic calcium phosphate ceramic. One of the calvarial defects was
      randomly protected with a PEG resorbable liquid membrane in each animal. Five
      animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen
      for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and
      did not receive any supplemental oxygen (normobaric). The animals were killed 6
      weeks after their surgery, and their parietal bones were harvested. The specimens
      were analyzed with microscopic computerized tomography (microCT) scans and
      histomorphometrics. RESULTS: The unfilled normobaric control bony defects did not
      heal, proving the critical-size nature of these defects. The presence of
      autogenous bone or bone ceramic in the defects increased the bone volume fraction
      and bone mineral density of the defects (P < .001). The presence of a membrane in
      the ungrafted and autogenous bone grafted defects resulted in a decrease in the
      corrected bone volume fraction (P = .002) but not in the bone ceramic grafted
      defects (P = .580). Bony healing of defects where the membrane was unsupported
      was compromised; the membrane did not maintain the desired bone regeneration
      volume with the unfilled and autogenous bone grafted groups. The PEG resorbable
      liquid membrane worked best with the bone ceramic material. HBO did not
      ameliorate the healing of the autogenous bone graft or ceramic filled defects in
      the 6-week time period of this study. CONCLUSIONS: Although the PEG resorbable
      liquid membrane is easy to use and forms an occlusive layer, caution is
      recommended when using the membrane over an unsupported defect. HBO did not
      ameliorate bony healing with the membrane at the early 6-week time point. The
      authors recommend future assessment with HBO at the 12-week time point.

PMID- 20060342
TI  - Parathyroid hormone-related peptide (PTHrP), parathyroid hormone/parathyroid
      hormone-related peptide receptor 1 (PTHR1), and MSX1 protein are expressed in
      central and peripheral giant cell granulomas of the jaws.
AB  - OBJECTIVE: Parathyroid hormone-related peptide (PTHrP) binds to the parathyroid
      hormone receptor type 1 (PTHR1), which results in the activation of pathways in
      osteoblasts that promote osteoclastogenesis through the RANK/RANKL system.
      RANK/RANKL expression has been shown in central giant cell granuloma of the jaws
      but PTHrP/PTHR1 has not. MSX1 protein is a classical transcription regulator
      which promotes cell proliferation and inhibits cell differentiation by inhibiting
      master genes in tissues such as bone and muscle. It has been implicated in the
      pathogenesis of cherubism, and its expression has been reported in a single
      central giant cell granuloma (CGCG) case. We aimed, therefore, to study the
      expression of those proteins by the different cellular populations of central and
      peripheral giant cell granulomas (PGCGs) of the jaws. STUDY DESIGN: Twenty cases
      of CGCG and 20 cases of PGCG of the jaws were retrospectively examined by
      immunohistochemistry for the percentage of positively staining cells to
      antibodies for PTHrP, PTHR1, and MSX1, using a semiquantitative method. RESULTS:
      In both CGCG and PGCG of the jaws, PTHrP and PTHR1 were abundantly expressed by
      type I multinucleated giant cells (MGC) and mononucleated stromal cells (MSC)
      with vesicular nuclei, whereas type II MGC and MSC with pyknotic nuclei expressed
      those proteins to a lesser extent. In both CGCG and PGCG of the jaws, MSX1 was
      abundantly expressed by type I MGC and MSC but type II MGC did not express it. A
      statistically significant difference (P < .05) was observed between CGCG and PGCG
      in the expression of PTHrP in type II MGC and MSC with pyknotic nuclei and in the
      expression of PTHR1 in type II MGC. CONCLUSIONS: We suggest that in CGCG and PGCG
      of the jaws, PTHrP-positive immature osteoblasts activate PTHR1-positive mature
      osteoblasts to produce RANKL which interacts with RANK on the PTHrP/PTHR1
      positive osteoclast-precursor cells found in abundance in the stroma of giant
      cell lesions and induces osteoclastogenesis through the classic pathway. Cells of
      the jawbones, the periodontal ligament, or the dental follicle, originating from
      the neural crest, may be involved in the pathogenesis of giant cell lesions of
      the jaws. Further study is required for these suggestions to be proved.

PMID- 20060343
TI  - The unappreciated Wnt-4 gene.

PMID- 20060344
TI  - Interresidue carbonyl-carbonyl polarization transfer experiments in uniformly
      13C,15N-labeled peptides and proteins.
AB  - In this work, we demonstrate that Homonuclear Rotary Resonance Recoupling
      (HORROR) can be used to reintroduce carbonyl-carbonyl interresidue dipolar
      interactions and to achieve efficient polarization transfer between carbonyl
      atoms in uniformly (13)C,(15)N-labeled peptides and proteins. We show that the
      HORROR condition is anisotropically broadened and overall shifted to higher radio
      frequency intensities because of the CSA effects. These effects are analyzed
      theoretically using Average Hamiltonian Theory. At spinning frequencies used in
      this study, 22kHz, this broadening is experimentally found to be on the order of
      a kilohertz at a proton field of 600MHz. To match HORROR condition over all
      powder orientations, variable amplitude radio frequency (RF) fields are required,
      and efficient direct transfers on the order of 20-30% can be straightforwardly
      established. Two- and three-dimensional chemical shift correlation experiments
      establishing long-range interresidue connectivities (e.g., (N[i]-CO[i-2])) are
      demonstrated on the model peptide N-acetyl-valine-leucine, and on the third
      immunoglobulin binding domain of protein G. Possible future developments are
      discussed.

PMID- 20060345
TI  - To the editor. Results with bilateral medial rectus muscle recession for
      unilateral esotropic Duane syndrome.

PMID- 20060346
TI  - Differential reactivity of thiophene-2-carboxylic and thiophene-3-carboxylic
      acids: Results from DFT and Hartree-Fock theory.
AB  - In the course of investigating the propensity of aromatic acids to react with
      selected nucleophiles, we came across an interesting difference in yields for two
      structurally similar thiophene carboxylic acids. Given that these yields were
      consistent across more than 40 repetitions for each structure, we felt that the
      difference was real, and worth exploration. To extract the potential steric and
      electronic origins of such differences, we employed both DFT B3LYP/6-31G* and
      HF/6-311+G** levels of theory to evaluate structures and energetics. Two somewhat
      different pictures emerge of the origin of the differences between the carboxylic
      acids and their individual conformations. In particular, Hartree-Fock
      calculations with the larger 6-311+G** basis set, which includes multiple diffuse
      functions, show a profound difference in the delocalization of the LUMO, relative
      to the DFT method which, expectedly, provides a more localized picture of the
      contributions to the LUMO. For each of the conformers, the molecular
      electrostatic potential and the ionization potential (ESP and IP, respectively),
      together with charge distributions, dipole moments and orbital energies have been
      explored. A potential explanation for the somewhat more reactive character of the
      thiophene-2-carboxylic acid appears to arise from the presence of a conformer
      which has an internal hydrogen bond to the thiophene sulfur, which, in turn,
      polarizes the acid function significantly relative to other conformers, and
      optimizes the angle of attack of the nucleophile.

PMID- 20060347
TI  - Robust modelling of solubility in supercritical carbon dioxide using Bayesian
      methods.
AB  - Two sparse Bayesian methods were used to derive predictive models of solubility
      of organic dyes and polycyclic aromatic compounds in supercritical carbon dioxide
      (scCO(2)), over a wide range of temperatures (285.9-423.2K) and pressures (60
      1400 bar): a multiple linear regression employing an expectation maximization
      algorithm and a sparse prior (MLREM) method and a non-linear Bayesian Regularized
      Artificial Neural Network with a Laplacian Prior (BRANNLP). A randomly selected
      test set was used to estimate the predictive ability of the models. The MLREM
      method resulted in a model of similar predictivity to the less sparse MLR method,
      while the non-linear BRANNLP method created models of substantially better
      predictivity than either the MLREM or MLR based models. The BRANNLP method
      simultaneously generated context-relevant subsets of descriptors and a robust,
      non-linear quantitative structure-property relationship (QSPR) model for the
      compound solubility in scCO(2). The differences between linear and non-linear
      descriptor selection methods are discussed.

PMID- 20060348
TI  - Growth hormone attenuates skeletal muscle changes in experimental chronic heart
      failure.
AB  - OBJECTIVE: This study evaluated the effects of growth hormone (GH) on morphology
      and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats
      with ascending aortic stenosis (AAS) induced chronic heart failure. DESIGN: Male
      90-100g Wistar rats were subjected to thoracotomy. AAS was created by placing a
      stainless-steel clip on the ascending aorta. Twenty five weeks after surgery,
      rats were treated with daily subcutaneous injections of recombinant human GH
      (2mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated
      animals served as controls. Left ventricular (LV) function was assessed before
      and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia,
      soleus muscle was frozen in liquid nitrogen. Histological sections were stained
      with HE and picrosirius red to calculate muscle fiber cross-sectional area and
      collagen fractional area, respectively. MRF myogenin and MyoD expression was
      analyzed by reverse transcription PCR. RESULTS: Body weight was similar between
      groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular
      (LV) hypertrophy (LV mass index: Control 1.90+/-0.15; AAS 3.11+/-0.44; AAS-GH
      2.94+/-0.47 g/kg; p<0.05 AAS and AAS-GH vs. Control), and reduced LV posterior
      wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS
      than in Control and AAS-GH groups; there was no difference between AAS-GH and
      Control groups. Collagen fractional area was significantly higher in AAS than
      Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1
      levels decreased in AAS compared to Control. MyoD mRNA was significantly higher
      in AAS-GH than AAS; there was no difference between AAS-GH and Control groups.
      Myogenin mRNA levels were similar between groups. CONCLUSION: In rats with aortic
      stenosis-induced heart failure, growth hormone administration increases MyoD gene
      expression above non-treated animal levels, preserves muscular trophism and
      attenuates interstitial fibrosis. These results suggest that growth hormone may
      have a potential role as an adjuvant therapy for chronic heart failure.

PMID- 20060349
TI  - Treatment of mitochondrial electron transport chain disorders: a review of
      clinical trials over the past decade.
AB  - While many treatments for mitochondrial electron transport (respiratory) chain
      disorders have been suggested, relatively few have undergone controlled clinical
      trials. This review focuses on the recent history of clinical trials of
      dichloroacetate (DCA), arginine, coenzyme Q(10), idebenone, and exercise in both
      primary (congenital) disorders and secondary (degenerative) disorders. Despite
      prior clinical impressions that DCA had a positive effect on mitochondrial
      disorders, two trials of diverse subjects failed to demonstrate a clinically
      significant benefit, and a trial of DCA in MELAS found a major negative effect of
      neuropathy. Arginine also has been used to treat MELAS with promising effects,
      although a controlled trial is still needed for this potentially toxic agent. The
      anti-oxidant coenzyme Q(10) is very widely used for primary mitochondrial
      disorders but has not yet undergone a controlled clinical trial; such a trial is
      now underway, as well as trials of the co-Q analogue idebenone for MELAS and
      LHON. Greater experience has accumulated with multi-center trials of coenzyme
      Q(10) treatment to prevent the progression of Parkinson disease. Although initial
      smaller trials indicated a benefit, this has not yet been confirmed in subsequent
      trials with higher doses; a larger Phase III trial is now underway. Similarly, a
      series of trials of idebenone for Friedreich ataxia have shown some benefit in
      slowing the progression of cardiomyopathy, and controlled clinical trials are now
      underway to determine if there is significant neurological protection.
      Uncontrolled trials of exercise showed an increase of exercise tolerance in
      patients with disorders of mitochondrial DNA, but did not selectively increase
      the percentage of normal mtDNA; a larger partially controlled trial is now
      underway to evaluate this possible benefit. In summary, none of the controlled
      trials so far has conclusively shown a benefit of treatment with the agents
      tested, but some promising therapies are currently being evaluated in a
      controlled manner. These experiences underscore the importance of controlled
      clinical trials for evaluation of benefits and risks of recommended therapies.
      Application of such clinical trials to future more effective therapies for
      mitochondrial disorders will require multi-center collaboration, organization,
      leadership, and financial and advocacy support.

PMID- 20060350
TI  - Hypovitaminosis D in glycogen storage disease type I.
AB  - Glycogen storage disease type I (GSD I) is caused by inherited defects of the
      glucose 6-phosphatase complex, resulting in fasting hypoglycemia, lactic
      acidosis, hyperuricemia and hyperlipidemia. Sixteen out of 26 (61.5%) GSD I
      patients in our study had suboptimal levels (<30 ng/ml) of 25-hydroxyvitamin-D
      (25(OH)D) despite supplementation of vitamin D and/or vitamin D + calcium based
      on WHO standards in 24/26 (92.3%) patients. The restrictive nature of the GSD I
      diet, metabolic derangements and intestinal malabsorption seen in GSD I are
      possible reasons for the observed hypovitaminosis D. Our results suggest that
      measurement of 25(OH)D should be considered in the routine evaluation of GSD I
      patients.

PMID- 20060351
TI  - Successes in the HIV epidemic response in Africa: maintaining momentum in
      uncertain times.

PMID- 20060352
TI  - Is there a link between seropositivity to Helicobacter pylori and hepatitis A
      virus? A systematic review.
AB  - BACKGROUND: Since hepatitis A virus (HAV) is acquired primarily through the fecal
      oral pathway, several investigators have used HAV seropositivity as a proxy for
      exposure to this pathway. This paper is a critical review of the evidence
      relevant to the association between seropositivity to HAV and Helicobacter
      pylori, and considers the validity of comparisons for testing the hypothesis that
      H. pylori spreads by the fecal-oral route. MATERIALS AND METHODS: A Medline
      search identified reports of all types published in the English language
      literature that were linked to the keywords 'Campylobacter pylori', 'hepatitis
      A', or 'Helicobacter pylori', cross-referenced with 'seroepidemiology',
      'seroprevalence', or 'seropositivity'. Studies identified by the search were
      included in the review if they used specific IgG antibodies to classify the
      serostatus of subjects for both HAV and H. pylori infection and provided an
      estimate of the magnitude of the association between HAV and H. pylori or
      information that permitted calculation of an odds ratio (OR). RESULTS: Out of the
      21 studies identified, 15 met the inclusion criteria. The studies showed ORs for
      an association of HAV and H. pylori that ranged from 0.81 to 8.4. After
      adjustment for potential confounders, ORs shifted toward the null. They also
      showed that HAV seroprevalence is lower than H. pylori seroprevalence in early
      life and then becomes higher in later life. Thus in most populations, the trends
      cross over at some point. CONCLUSION: The observed associations between the two
      infections are generally overestimated by the confounding effects of age and
      socio-economic status-related factors, and when these factors are controlled, the
      association becomes weak. Moreover, HAV infection elicits a long-term antibody
      response, while H. pylori infection does not. Consequently, serostatus comparison
      does not constitute a convincing test of the fecal-oral transmission hypothesis
      for H. pylori.

PMID- 20060353
TI  - A new pilot flow reactor for high-intensity ultrasound irradiation. Application
      to the synthesis of biodiesel.
AB  - In recent years, chemistry in flowing systems has become more prominent as a
      method of carrying out chemical transformations, ranging in scale from
      microchemistry up to kilogram-scale processes. Compared to classic batch
      ultrasound reactors, flow reactors stand out for their greater efficiency and
      flexibility as well as lower energy consumption. This paper presents a new
      ultrasonic flow reactor developed in our laboratory, a pilot system well suited
      for reaction scale up. This was applied to the transesterification of soybean oil
      with methanol for biodiesel production. This reaction is mass-transfer-limited
      initially because the two reactants are immiscible with each other, then because
      the glycerol phase separates together with most of the catalyst (Na or K
      methoxide). In our reactor a mixture of oil (1.6 L), methanol and sodium
      methoxide 30% in methanol (wt/wt ratio 80:19.5:0.5, respectively) was fully
      transesterified at about 45 degrees C in 1h (21.5 kHz, 600 W, flow rate 55
      mL/min). The same result could be achieved together with a considerable reduction
      in energy consumption, by a two-step procedure: first a conventional heating
      under mechanical stirring (30 min at 45 degrees C), followed by ultrasound
      irradiation at the same temperature (35 min, 600 W, flow rate 55 mL/min). Our
      studies confirmed that high-throughput ultrasound applications definitively
      require flow reactors.

PMID- 20060354
TI  - Study of FHIT and WWOX expression in mucoepidermoid carcinoma and adenoid cystic
      carcinoma of salivary gland.
AB  - Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary
      gland neoplasms with divergent morphological features and clinical behavior. ACC
      is a basaloid tumor whereas MEC is a glandular epithelial neoplasm. FHIT and WWOX
      are tumor suppressor genes that encompass the FRA3B and FRA16D fragile sites at
      chromosomes 3p14.2 and 16q23.3, respectively. In previous studies, we have shown
      concordant loss of Fhit and Wwox expression in breast cancer, with significantly
      more frequent loss in cancers of basal-like phenotype. To determine if there is a
      similar association in salivary gland neoplasms, we designed a study of MEC and
      ACC of salivary gland on tissue microarrays (TMA). TMAs were constructed from 25
      MEC and 19 ACC of salivary gland. Fhit and Wwox protein expression was assessed
      by immunohistochemical staining of cores on TMAs. Correlations among
      immunohistochemical markers and histological type were determined by statistical
      analyses. Significantly reduced Fhit and Wwox expression was observed in ACC
      (p=0.002 and p<0.001, respectively). The results suggest that, as for breast
      cancer, loss of Fhit and Wwox expression might have a role in the pathogenesis of
      basaloid differentiation in salivary gland neoplasms; alternatively, differences
      in chromatin structure at chromosome fragile regions might make fragile genes
      more accessible to DNA damage and rearrangement early during preneoplastic stages
      of basaloid cancers. Studies of basaloid tumors of other organ systems may show
      similar results and these findings may have implications for treatment modalities
      designed for basal-like tumors.

PMID- 20060355
TI  - The clinicopathological significance of the expression of Granzyme B in oral
      squamous cell carcinoma.
AB  - Granzyme B (GB) is a serine protease synthesized by activated cytotoxic T
      lymphocytes and natural killer cells that induces neoplastic cells apoptosis. The
      expression of GB in the tumor microenvironment has been considered a favorable
      prognostic factor in several types of human cancers. Thus, the aim of this study
      was to evaluate the density of GB(+) cells in samples of oral cavity squamous
      cell carcinoma (OCSCC), as well as their relationship with clinical and
      microscopic parameters. GB expression was analyzed in 55 cases of OCSCC and
      metastatic and non-metastatic lymph nodes by means of immunohistochemistry. The
      high density of GB(+) cells demonstrated an association with the high percentage
      of Bax(+) and annexin V(+) neoplastic cells. In addition, the number of
      peritumoral GB(+) cells was significantly higher in the OCSCC group without lymph
      node metastasis, when compared with the metastatic OCSCC group. Moreover,
      patients with OCSCC with a high density of peritumoral GB(+) cells showed a
      longer survival time when compared with patients with a lower density of these
      cells. In lymph node tissues, the density of GB(+) cells was significantly higher
      in non-metastatic lymph nodes than in metastatic lymph nodes. Our findings
      suggest that the increased of expression of GB in the tumor microenvironment of
      OCSCC and in lymph nodes may have beneficial effect against neoplastic cells,
      contributing to apoptosis of these cells and increased survival of patients.

PMID- 20060356
TI  - Downregulation of CD9 protein expression is associated with aggressive behavior
      of oral squamous cell carcinoma.
AB  - Squamous cell carcinoma of the oral cavity (OSCC) is a malignancy characterized
      by a high degree of local aggression and metastasis to cervical lymph nodes.
      Tetraspanins are proteins with functional roles in a wide array of cellular
      processes and are reported to be associated with tumor progression. The present
      study investigated the expression of the CD9, CD37, CD63, CD81 and CD82
      tetraspanins in OSCC using immunohistochemistry (IHC) and quantitative Real Time
      PCR (qRT-PCR). Tissue microarray (TMA) analysis of samples from 179 cases of OSCC
      and 10 normal samples oral mucosa were evaluated immunomorphologically. We
      analyzed CD9 and CD82 expression by qRT-PCR in 66 OSCC cases and 4 normal samples
      of oral mucosa. Expression of CD63, CD37 and CD81 was not detected in the samples
      studied. CD82 was downregulated or negative in 127 of 179 (80%) specimens; no
      correlation was observed between CD82 expression, clinicopathological parameters,
      disease-free survival and 5-year overall survival. CD9 expression was
      downregulated or negative in 75 of 129 (42%) OSCC samples. Loss of CD9 expression
      in OSCC samples correlated with the incidence of lymph node metastasis (p=0.017).
      Disease-free survival and the 5-year overall survival of patients with
      downregulated or negative CD9 expression were significantly lower than in
      patients with positive CD9 expression (p=0.010 and p=0.071, respectively). No
      correlation was found between CD9 or CD82 expression and clinicopathological
      parameters by qRT-PCR. Our results suggest that the downregulation or lack of
      expression of the CD9 protein might indicate a more aggressive of OSCC.

PMID- 20060357
TI  - Influence of class M1 glutathione S-transferase (GST Mu) polymorphism on GST M1
      gene expression level and tumor size in oral squamous cell carcinoma.
AB  - Glutathione S-transferases (GST) are antioxidant enzymes and oxidative stress
      markers in oral carcinogenesis. They present a system of polymorphic proteins.
      Some variants are associated with increased sensitivity to toxic compounds, as it
      is known for the GSTM1-null variant allele. However, the influence of the GSTM1
      allele variant genotype on GSTM1-mRNA quantity in oral squamous cell carcinoma
      (OSCC) and normal mucosa as well as the impact on prognosis remains unclear. The
      genotype for GSTM1 (mutation vs. wild type) was determined by polymerase chain
      reaction (PCR) using genomic DNA extracted from peripheral blood from 28 OSCC
      patients. From the same patients, 28 pairs of OSCC cells and normal oral mucosal
      cells were obtained by brush biopsy. mRNA was extracted from these paired samples
      and the expression levels of GSTM1 were examined by real-time reverse
      transcriptase qPCR (RT-qPCR). The mRNA expression of the OSCC samples was
      normalized against an external standard, as well as to the corresponding normal
      mucosa. The coincidence of GSTM1 genotype and GSTM1-mRNA-expression level was
      examined. In 15 patients (54%), the null genotype GSTM1 was present. In the GSTM1
      null allele group, the GSTM1 gene expression level was determined at 1.63 (mean:
      3.08; SD 3.4) folds vs. 3.6 (mean: 10.5; SD 14.2) folds in the group with the
      positive genotype (p=0.06), if calibrated vs. individual normal mucosa. More T3
      and T4 OSCCs (+38%), higher UICC stadia (+38%) and more lymphatic metastasis
      (+28%) were seen in the group with the negative allele. Furthermore, positive
      GSTM1 genotype and enhanced GSTM1 gene expression was accompanied with increased
      tumor size, lymphatic metastasis status and UICC stadium. A coincidence of null
      type GSTM1 and lowered GSTM1 gene expression was observed. The larger tumors and
      more frequent lymph node metastases in this group could be explained by the
      insufficient cell protection by GST.

PMID- 20060358
TI  - A novel visible spectrophotometric method for the determination of ethamsylate in
      pharmaceutical preparations and biological samples.
AB  - A highly sensitive visible spectrophotometric method has been developed to
      determine ethamsylate in this paper, which is based on using Cu(II) as
      spectroscopic probe reagent. The study indicates that in the presence of SCN(-)
      and KNO(3), Cu(II) is reduced to Cu(I) by ethamsylate at pH 5.0, and the in situ
      formed Cu(I) reacts with SCN(-) to form into the white emulsion CuSCN that could
      be stayed upon the surface of water. According to the amount of residual Cu(II),
      the amount of ethamsylate can be indirectly determined. Under the optimal
      conditions, Beer's law is applicable in the range of 0.2-9.0 microg/mL (7.60x10(
      7)-3.42x10(-5)mol/L) for aqueous standard solution of ethamsylate with linear
      correlation coefficient of 0.9998. The detection limit and relative standard
      deviation are 0.12 microg/mL and 1.5%, respectively. And the molar absorption
      coefficient of the indirect determination of ethamsylate is 1.0x10(5)L/mol cm.
      The method is successfully applied to determine ethamsylate in pharmaceutical
      preparations and biological samples.

PMID- 20060359
TI  - Analysis of phenanthrene biodegradation by using FTIR, UV and GC-MS.
AB  - The aim of this paper is to assess the biodegradation of phenanthrene by
      Flavobacteria FCN2 which was isolated from coke plant sludge via a classical
      shaken liquid medium enrichment method. The strain FCN2 can decompose
      phenanthrene (50 mg l(-1)) completely within 5 days. The values of pH decrease to
      6.7 from 7.2 during degradation periods. And a detailed phenanthrene metabolism
      was assayed by using FTIR, UV and GC-MS. For FTIR, appearance of new broad
      absorption bands at 2858 cm(-1), 2927 cm(-1), 2955 cm(-1) and another new strong
      absorption band at 1734 cm(-1) in metabolites demonstrates that carboxyl group
      produced during phenanthrene degradation. Besides this, a very strong absorption
      band appears at 1260 cm(-1). It is ascribed to C-C stretching vibration band in
      carbonyl group of arone. Two weak adsorption at 334 nm and 349 nm in UV spectra
      were assigned to the n-pi* transition of CO of aldehyde. Two metabolites,
      phenanthrene-dihydrodiol and naphthalene-1-diol were identified in neutral
      fraction of phenanthrene degradation by using GC-MS. As a result carboxylic acids
      and arone were generated during biodegradation of phenanthrene by Flavobacteria
      FCN2.

PMID- 20060360
TI  - Human polyoma viruses and disease with emphasis on clinical BK and JC.
AB  - Polyoma viruses are ubiquitous infecting many different mammalian species
      including humans. There are five known human polyoma viruses. JC virus and BK
      virus are two polyoma viruses identified nearly three decades ago. Recently WU,
      KI and Merkel cell polyoma viruses have been isolated from humans. The exact role
      of these three newly discovered viruses in human disease is not known. Most human
      polyoma disease is caused by BK and JC viruses which are usually acquired in
      childhood. Approximately 50-80% of humans have seropositivity to these viruses.
      Clinically apparent diseases in immunocompetent hosts are extremely rare. These
      viruses remain latent possibly in the lymphoid organs, neuronal tissue, and
      kidney and under the circumstances of severe immunosuppression both these viruses
      reactivate. Neurotropic JC virus reaches the brain and causes progressive
      multifocal leukoencephalopathy, a demyelinating disease of the central nervous
      system with a high mortality rate. BK virus is urotheliotropic and its
      reactivation causes a form of interstitial nephritis, known as BK or polyoma
      virus associated nephropathy which is associated with high graft loss if not
      recognized early. There are no known effective antiviral agents for any of the
      polyoma viruses.

PMID- 20060361
TI  - Novel aspects of the roles of Rac1 GTPase in the cardiovascular system.
AB  - Rac1 GTPase is an established master regulator of cell motility through cortical
      actin re-organization and of reactive oxygen species generation through
      regulation of NADPH oxidase activity. Numerous molecular and cellular studies
      have implicated Rac1 in various cardiovascular pathologies: vascular smooth
      muscle proliferation, cardiomyocyte hypertrophy, and endothelial cell shape
      change. The physiological relevance of these in vitro findings, however, is just
      beginning to be reassessed with the newly developed, conditional mouse
      mutagenesis technology. Conditional gene targeting has also revealed unexpected,
      cell type-specific roles of Rac1. The aim of this review is to summarize the
      recent advance made in Rac1 research in the cardiovascular system, with special
      focus on its novel roles in the regulation of endothelial function, angiogenesis,
      and endothelium-mediated neuroprotection.

PMID- 20060362
TI  - Crosstalk between perivascular adipose tissue and blood vessels.
AB  - Crosstalk between cells in the blood vessel wall is vital to normal vascular
      function and is perturbed in diseases such as atherosclerosis and hypertension.
      Perivascular adipocytes reside at the adventitial border of blood vessels but
      until recently were virtually ignored in studies of vascular function. However,
      perivascular adipocytes have been demonstrated to be powerful endocrine cells
      capable of responding to metabolic cues and transducing signals to adjacent blood
      vessels. Accordingly, crosstalk between perivascular adipose tissue (PVAT) and
      blood vessels is now being intensely examined. Emerging evidence suggests that
      PVAT regulates vascular function through numerous mechanisms, but evidence to
      date suggests modulation of three key aspects that are the focus of this review:
      inflammation, vasoreactivity, and smooth muscle cell proliferation.

PMID- 20060363
TI  - TRP channels and the control of vascular function.
AB  - Mammalian TRP channels are grouped into six subfamilies (TRPC, TRPM, TRPV, TRPA,
      TRPP, and TRPML) based on the homology of the amino acid sequence. They are
      nonselective cation-permeable channels, most of which are permeable for Ca(2+).
      Growing evidence demonstrates important roles of TRP channel in controlling
      vascular function including endothelial permeability, responses to oxidative
      stress, myogenic tone, cellular proliferative activity, and thermoregulation. TRP
      channels are activated by a variety of stimuli, including calcium store
      depletion, mechanical perturbations, receptor activation, and changes in
      temperature and osmolarity. This diversity of activating mechanisms could be
      consistent with the potential multiple functions of the TRP superfamily. This
      review summarizes the burgeoning understanding of these cation channels in the
      control of vascular function.

PMID- 20060364
TI  - Resolution and uniqueness of estimated parameters of a model of thin filament
      regulation in solution.
AB  - The estimation of chemical kinetic rate constants for any non-trivial model is
      complex due to the nonlinear effects of second order chemical reactions. We
      developed an algorithm to accomplish this goal based on the Damped Least Squares
      (DLS) inversion method and then tested the effectiveness of this method on the
      McKillop-Geeves (MG) model of thin filament regulation. The kinetics of MG model
      is defined by a set of nonlinear ordinary differential equations (ODEs) that
      predict the evolution of troponin-tropomyosin-actin and actin-myosin states. The
      values of the rate constants are estimated by integrating these ODEs numerically
      and fitting them to a series of stopped-flow pyrene fluorescence transients of
      myosin-S1 fragment binding to regulated actin in solution. The accuracy and
      robustness of the estimated rate constants are evaluated for DLS and two other
      methods, namely quasi-Newton (QN) and simulated annealing (SA). The comparison of
      these methods revealed that SA provides the best estimates of the model
      parameters because of its global optimization scheme. However it converges slowly
      and does quantify the uniqueness of the estimated parameters. On the other hand
      the QN method converges rapidly but only if the initial guess of the parameters
      is close to the optimum values, otherwise it diverges. Overall, the DLS method
      proves to be the most convenient method. It converges fast and was able to
      provide excellent estimates of kinetic parameters. Furthermore, DLS provides the
      model resolution matrix, which quantifies the interdependence of model parameters
      thereby evaluating the uniqueness of their estimated values. This property is
      essential for estimating of the dependence of the model parameters on
      experimental conditions (e.g. Ca(2+) concentration) when it is assessed from
      noisy experimental data such as pyrene fluorescence from stopped-flow transients.
      The advantages of the DLS method observed in this study should be further
      examined in other physicochemical systems to firmly establish the observed
      effectiveness of DSL vs. the other parameter estimation methods.

PMID- 20060365
TI  - DNA methylation signatures identify biologically distinct subtypes in acute
      myeloid leukemia.
AB  - We hypothesized that DNA methylation distributes into specific patterns in cancer
      cells, which reflect critical biological differences. We therefore examined the
      methylation profiles of 344 patients with acute myeloid leukemia (AML).
      Clustering of these patients by methylation data segregated patients into 16
      groups. Five of these groups defined new AML subtypes that shared no other known
      feature. In addition, DNA methylation profiles segregated patients with CEBPA
      aberrations from other subtypes of leukemia, defined four epigenetically distinct
      forms of AML with NPM1 mutations, and showed that established AML1-ETO, CBFb
      MYH11, and PML-RARA leukemia entities are associated with specific methylation
      profiles. We report a 15 gene methylation classifier predictive of overall
      survival in an independent patient cohort (p < 0.001, adjusted for known
      covariates).

PMID- 20060366
TI  - The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion
      leads to chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is a malignancy of B cells of unknown
      etiology. Deletions of the chromosomal region 13q14 are commonly associated with
      CLL, with monoclonal B cell lymphocytosis (MBL), which occasionally precedes CLL,
      and with aggressive lymphoma, suggesting that this region contains a tumor
      suppressor gene. Here, we demonstrate that deletion in mice of the 13q14-minimal
      deleted region (MDR), which encodes the DLEU2/miR-15a/16-1 cluster, causes
      development of indolent B cell-autonomous, clonal lymphoproliferative disorders,
      recapitulating the spectrum of CLL-associated phenotypes observed in humans. miR
      15a/16-1-deletion accelerates the proliferation of both human and mouse B cells
      by modulating the expression of genes controlling cell-cycle progression. These
      results define the role of 13q14 deletions in the pathogenesis of CLL.

PMID- 20060367
TI  - Mesenteric venous thrombosis after laparoscopic sleeve gastrectomy.

PMID- 20060368
TI  - Gastrocolic fistula after re-sleeve gastrectomy: outcomes after esophageal stent
      implantation.

PMID- 20060369
TI  - PCNA-coupled p21 degradation after DNA damage: The exception that confirms the
      rule?
AB  - While many are the examples of DNA damaging treatments that induce p21
      accumulation, the conception of p21 upregulation as the universal response to
      genotoxic stress has come to an end. Compelling evidences have demonstrated the
      existence of converging signals that negatively regulate p21 bellow basal levels
      when replication forks are blocked. Moreover, conclusive reports identified the
      E3-ligase CRL4(CDT2) (CUL4-DDB1-CDT2) as the enzymatic complex that promotes p21
      proteolysis when treatments such as UV irradiation trigger replication fork
      stress. A pre-requisite for CRL4(CDT2)-driven proteolysis is the interaction of
      p21 with PCNA. Interestingly as well, CRL4(CDT2)-dependent proteolysis is not
      limited to p21 and affects other PCNA partners, including the specialized DNA
      polymerase eta (pol eta). These recent discoveries are particularly intriguing
      since the UV-induced degradation of p21 has been shown to be required for
      efficient pol eta recruitment to DNA lesions. Herein we review the findings that
      lead to the identification of the molecular mechanism that triggers damage
      induced PCNA-coupled protein proteolysis. We propose a novel model in which
      CRL4(CDT2)-dependent protein degradation facilitates a sequential and dynamic
      exchange between PIP box bearing proteins at stall forks during Translesion DNA
      synthesis (TLS). Moreover, given the tight spatiotemporal control that CRL4(CDT2)
      driven proteolysis is able to confer to PCNA-regulated processes, we discuss the
      impact that this degradation mechanism might have in other molecular switches
      associated with the repair of damaged DNA.

PMID- 20060372
TI  - Treatment of sagittal synostosis: subtotal cranial vault remodelling with right
      angled Z-osteotomies.
AB  - INTRODUCTIONS: Sagittal synostosis is the most common type of non-syndromic
      craniosynostosis with fusion of the sagittal suture. Various techniques have been
      introduced for the treatment of this irregular calvarial deformity. However,
      since these methods were not suitable for patients who were aged over 1 year when
      they were diagnosed with sagittal synostosis, a new approach should be
      undertaken. PATIENTS AND METHODS: Between 2001 and 2005, five patients who were
      diagnosed with sagittal synostosis, after the age of 1 year, were treated with
      subtotal cranial vault remodelling. The procedure consisted of right-angled Z
      osteotomies in the frontal and parieto-occipital bones, a shortening of the
      sagittal strut, and barrel-stave osteotomies in the temporal bone. They were
      undertaken to expand bitemporal diameter and to shorten anteroposterior diameter.
      RESULTS: Cranial index increased from 68.2 to 77.8 immediately after surgery and
      to 78.4 post-surgery 36 months. Cranial morphologies were satisfactory during
      follow-up. The main advantage of the procedure is the easy control of fixation
      angle according to the surgeon's preference. There were no major complications
      including infections or relapses. CONCLUSIONS: The treatment goal of sagittal
      synostosis is to eliminate factors that may impede brain development by assuring
      an adequate cranial cavity and to maintain an aesthetically acceptable cranial
      morphology. We obtained functionally and aesthetically favourable results by
      right-angled Z-osteotomies. Further, our one-staged procedure is safe, especially
      in patients over the age of 1 year.

PMID- 20060370
TI  - Glycan gene expression signatures in normal and malignant breast tissue; possible
      role in diagnosis and progression.
AB  - Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide
      chains to proteins or lipids, and alterations in this process have been
      associated with malignant transformation. Simultaneous analysis of the expression
      of all glycan-related genes clearly gives the advantage of enabling a
      comprehensive view of the genetic background of the glycobiological changes in
      cancer cells. Studies focusing on the expression of the whole glycome have now
      become possible, which prompted us to review the present knowledge on
      glycosylation in relation to breast cancer diagnosis and progression, in the
      light of available expression data from tumors and breast tissue of healthy
      individuals. We used various data resources to select a set of 419 functionally
      relevant genes involved in synthesis, degradation and binding of N-linked and O
      linked glycans, Lewis antigens, glycosaminoglycans (chondroitin, heparin and
      keratan sulfate in addition to hyaluronan) and glycosphingolipids. Such glycans
      are involved in a number of processes relevant to carcinogenesis, including
      regulation of growth factors/growth factor receptors, cell-cell adhesion and
      motility as well as immune system modulation. Expression analysis of these glycan
      related genes revealed that mRNA levels for many of them differ significantly
      between normal and malignant breast tissue. An associative analysis of these
      genes in the context of current knowledge of their function in protein
      glycosylation and connection(s) to cancer indicated that synthesis, degradation
      and adhesion mediated by glycans may be altered drastically in mammary
      carcinomas. Although further analysis is needed to assess how changes in mRNA
      levels of glycan genes influence a cell's glycome and the precise role that such
      altered glycan structures play in the pathogenesis of the disease, lessons drawn
      from this study may help in determining directions for future research in the
      rapidly-developing field of glycobiology.

PMID- 20060371
TI  - Intrahepatic IgG/IgM plasma cells ratio helps in classifying autoimmune liver
      diseases.
AB  - BACKGROUND/AIM: Plasma cells infiltrate in the liver is a prototype lesion of
      autoimmune liver diseases. The possible role of plasma cells isotyping (IgM and
      IgG) in the liver in the diagnostic definition of autoimmune liver disease, and
      particularly in variant syndromes such as autoimmune cholangitis and the primary
      biliary cirrhosis/autoimmune hepatitis overlap syndrome, is less defined.
      METHODS: We analysed the clinical, serological and histological features of 83
      patients with autoimmune liver disease (40 primary biliary cirrhosis, 20
      autoimmune hepatitis, 13 primary sclerosing cholangitis, 4 autoimmune cholangitis
      and 6 overlap syndrome) compared to 34 patients with chronic hepatitis C and
      evaluated the expression of IgM and IgG plasma cells in their liver by
      immunostaining. RESULTS: By Spearman's correlation, the mean-counts of IgM plasma
      cells in portal tracts were significantly correlated with female gender, serum
      alkaline phosphatase, gamma-glutamyl transferase and IgM values, positivity for
      anti-mitochondrial antibody-M2 and, on liver biopsy, with bile duct changes,
      orcein-positive granules and granulomas. Whereas IgG plasma cells resulted more
      correlated with alanine aminotransferase levels. IgG/IgM ratio lower than 1 was
      found no only in primary biliary cirrhosis but also in all patients with
      autoimmune cholangitis. Conversely, all patients with overlap syndrome showed
      IgG/IgM ratio higher than 1. CONCLUSION: Immunostaining for IgM and IgG plasma
      cells on liver tissue can be a valuable parameter for better diagnosis of
      autoimmune liver disease and also for variant or mixed syndromes.

PMID- 20060373
TI  - Fourier transform infrared microspectroscopy identifies early lineage commitment
      in differentiating human embryonic stem cells.
AB  - Human ESCs (hESCs) are a valuable tool for the study of early human development
      and represent a source of normal differentiated cells for pharmaceutical and
      biotechnology applications and ultimately for cell replacement therapies. For all
      applications, it will be necessary to develop assays to validate the efficacy of
      hESC differentiation. We explored the capacity for FTIR spectroscopy, a technique
      that rapidly characterises cellular macromolecular composition, to discriminate
      mesendoderm or ectoderm committed cells from undifferentiated hESCs. Distinct
      infrared spectroscopic "signatures" readily distinguished hESCs from these early
      differentiated progeny, with bioinformatic models able to correctly classify over
      97% of spectra. These data identify a role for FTIR spectroscopy as a new
      modality to complement conventional analyses of hESCs and their derivatives. FTIR
      spectroscopy has the potential to provide low-cost, automatable measurements for
      the quality control of stem and differentiated cells to be used in industry and
      regenerative medicine.

PMID- 20060374
TI  - Selection of pfmdr1 and pfcrt alleles in amodiaquine treatment failure in north
      western Burkina Faso.
AB  - In 111 children under five years of age and with uncomplicated malaria in Nouna,
      north-western Burkina Faso, amodiaquine treatment failed in 75% (after PCR-based
      exclusion of new infections, 32%). In these, we assessed the role of Plasmodium
      falciparum pfmdr1 and pfcrt polymorphisms in amodiaquine resistance. Except for
      pfmdr1 1246Y (prevalence, 5%), no P. falciparum allele predicted treatment
      outcome. Pfcrt 76T as well as pfmdr1 86Y, 86Y-184F-1246D, and 86Y-184Y-1246Y were
      positively selected in treatment failures, and pfmdr1 86N-184F-1246D negatively.
      The weak association of pfmdr1/pfcrt alleles with amodiaquine treatment outcome
      suggests further factors to be involved in the unsatisfactory low efficacy of the
      drug and limits the usefulness of these markers in this area.

PMID- 20060375
TI  - Near-fixation of a Pfmsp1 block 2 allelic variant in genetically diverse
      Plasmodium falciparum populations across Western Colombia.
AB  - Assessment of the genetic diversity of Plasmodium falciparum in 110 Colombian
      isolates revealed that nearly all the parasites in the 97 isolates collected in
      endemic regions west of the Andes shared the same Pfmsp1 block 2 MAD20-type
      allelic variant, despite showing high diversity for other genetical markers.
      Analysis of published data indicated that the prevalence of this allelic variant
      of a major vaccine candidate antigen was already dominant since 1998. This
      phenomenon, which had not been hitherto recorded for a malaria blood stage
      antigen, is of biological and immunological interest but remains unexplained.

PMID- 20060376
TI  - Direct red 81 and amido black stain proteins in polyacrylamide electrophoresis
      gels within 10 min.
AB  - Proteins separated by SDS-polyacrylamide gel electrophoresis can be stained with
      organic dyes, the most popular being Coomassie brilliant blue R-250. Coomassie R
      250 staining of ovalbumin in an SDS-PAGE gel increased linearly from 2.5 to 60
      min. Direct red 81 and amido black staining approached saturation in 10 min.
      Scatchard analysis showed that the number of direct red 81 and amido black
      ligands bound to ovalbumin was fourfold higher than that of Coomassie R-250.
      Direct red 81 and amido black stain proteins in an SDS-polyacrylamide
      electrophoresis gel in 10 min.

PMID- 20060377
TI  - Molluscan twitchin can control actin-myosin interaction during ATPase cycle.
AB  - The effect of twitchin, a thick filament protein of molluscan muscles, on actin
      myosin interaction at several mimicked sequential steps of the ATPase cycle was
      investigated using fluorescent probes specifically bound to Cys707 of myosin
      subfragment-1 and Cys374 of actin incorporated into ghost muscle fibers. The
      multi-step changes in mobility and spatial arrangement of myosin SH1 helix and
      actin subdomain-1 during the ATPase cycle have been revealed. For the first time,
      the inhibition of movement of myosin SH1 helix and actin subdomain-1 during the
      ATPase cycle and the decrease in the myosin head and actin affinity in the
      presence of unphosphorylated twitchin have been demonstrated. Phosphorylation of
      twitchin by the catalytic subunit of protein kinase A reversed this effect. These
      data imply a novel property of twitchin consisting in its ability to regulate in
      a phosphorylation-dependent manner the actin-myosin interaction during the ATPase
      cycle by the inhibition of transformation of the weak-binding actomyosin states
      into the strong-binding ones.

PMID- 20060378
TI  - Liquid-ordered phases induced by cholesterol: a compendium of binary phase
      diagrams.
AB  - Mixtures of phospholipids with cholesterol are able to form liquid-ordered phases
      that are characterised by short-range orientational order and long-range
      translational disorder. These L(o)-phases are distinct from the liquid
      disordered, fluid L(alpha)-phases and the solid-ordered, gel L(beta)-phases that
      are assumed by the phospholipids alone. The liquid-ordered phase can produce
      spatially separated in-plane fluid domains, which, in the form of lipid rafts,
      are thought to act as platforms for signalling and membrane sorting in cells. The
      areas of domain formation are defined by the regions of phase coexistence in the
      phase diagrams for the binary mixtures of lipid with cholesterol. In this paper,
      the available binary phase diagrams of lipid-cholesterol mixtures are all
      collected together. It is found that there is not complete agreement between
      different determinations of the phase diagrams for the same binary mixture. This
      can be attributed to the indirect methods largely used to establish the phase
      boundaries. Intercomparison of the various data sets allows critical assessment
      of which phase boundaries are rigorously established from direct evidence for
      phase coexistence.

PMID- 20060379
TI  - Oxidatively modified fatty acyl chain determines physicochemical properties of
      aggregates of oxidized phospholipids.
AB  - In vivo oxidation of glycerophospholipid generates a variety of products
      including truncated oxidized phospholipids (tOx-PLs). The fatty acyl chains at
      the sn-2 position of tOx-PLs are shorter in length than the parent non-oxidized
      phospholipids and contain a polar functional group(s) at the end. The effect of
      oxidatively modified sn-2 fatty acyl chain on the physicochemical properties of
      tOx-PLs aggregates has not been addressed in detail, although there are few
      reports that modified fatty acyl chain primarily determines the biological
      activities of tOx-PLs. In this study we have compared the properties of four
      closely related tOx-PLs which differ only in the type of modified fatty acyl
      chain present at the sn-2 position: 1-palmitoyl-2-azelaoyl-sn-glycero-3
      phosphocholine (PazePC), 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3
      phosphocholine (PoxnoPC), 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine
      (PGPC), and 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC).
      Aggregates of individual tOx-PL in aqueous solution were characterized by
      fluorescence spectroscopy, size exclusion chromatography, native polyacrylamide
      and agarose gel electrophoresis. The data suggest that aggregates of four closely
      related tOx-PLs form micelle-like particles of considerably different properties.
      Our result provides first direct evidence that because of the specific chemical
      composition of the sn-2 fatty acyl chain aggregates of particular tOx-PL possess
      a distinctive set of physicochemical properties.

PMID- 20060380
TI  - miR-27a is a negative regulator of adipocyte differentiation via suppressing
      PPARgamma expression.
AB  - microRNAs (miRNAs) are non-coding small RNAs regulating gene expression, cell
      growth, and differentiation. Although several miRNAs have been implicated in cell
      growth and differentiation, it is barely understood their roles in adipocyte
      differentiation. In the present study, we reveal that miR-27a is involved in
      adipocyte differentiation by binding to the PPARgamma 3'-UTR whose sequence
      motifs are highly conserved in mammals. During adipogenesis, the expression level
      of miR-27a was inversely correlated with that of adipogenic marker genes such as
      PPARgamma and adiponectin. In white adipose tissue, miR-27a was more abundantly
      expressed in stromal vascular cell fraction than in mature adipocyte fraction.
      Ectopic expression of miR-27a in 3T3-L1 pre-adipocytes repressed adipocyte
      differentiation by reducing PPARgamma expression. Interestingly, the level of miR
      27a in mature adipocyte fraction of obese mice was down-regulated than that of
      lean mice. Together, these results suggest that miR-27a would suppress adipocyte
      differentiation through targeting PPARgamma and thereby down-regulation of miR
      27a might be associated with adipose tissue dysregulation in obesity.

PMID- 20060381
TI  - A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon
      cancer cells.
AB  - Many studies have demonstrated that histone deacetylase (HDAC) inhibitors induce
      various tumor cells to undergo apoptosis, and such inhibitors have been used in
      different clinical trials against different human cancers. In this study, we
      designed and synthesized a novel HDAC inhibitor, Chidamide. We showed that
      Chidamide was able to increase the acetylation levels of histone H3 and to
      inhibit the PI3K/Akt and MAPK/Ras signaling pathways, which resulted in arresting
      colon cancer cells at the G1 phase of the cell cycle and promoting apoptosis. As
      a result, the proliferation of colon cancer cells was suppressed in vitro. Our
      data support the potential application of Chidamide as an anticancer agent in
      treating colon cancer. Future studies are needed to demonstrate its in vivo
      efficacy.

PMID- 20060382
TI  - Angiopoietin-1/Tie2 signaling pathway inhibits lipopolysaccharide-induced
      activation of RAW264.7 macrophage cells.
AB  - Angiopoietin-1 (Ang1) is a ligand for the endothelial-specific tyrosine kinase
      receptor Tie2 and has been shown to play an essential role in embryonic
      vasculature development. There have been many studies about the anti-inflammatory
      effects of Ang1, most of which focus on endothelium cells. In the present study,
      we explore the role of Ang1-Tie2 signaling in the activation of macrophages upon
      lipopolysaccharide (LPS) stimulation. We found that Tie2 receptor is expressed on
      macrophages and Ang1 could inhibit LPS-induced activation of macrophages, as
      evidenced by cell migration and TNF-alpha production, specifically through Tie2
      receptor. We further investigated the mechanism and found that Ang1-Tie2 could
      block LPS-induced activation of NF-kappaB which has been shown to be necessary
      for macrophage activation with LPS treatment. Thus, we described, for the first
      time, the role of Ang1-Tie2 signaling in macrophage activation and the possible
      mechanisms in response to immune stimulation.

PMID- 20060383
TI  - Crystal structure of non-redox regulated SSADH from Escherichia coli.
AB  - SSADH is involved in the final step of GABA degradation, converting SSA to
      succinic acid in the human mitochondrial matrix, and its activity is known to be
      regulated via 'redox-switch modulation' of the catalytic loop. We present the
      crystal structure of EcSSADH, revealing that the catalytic loop of EcSSADH,
      unlike that of human SSADH, does not undergo disulfide bond-mediated structural
      changes upon changes of environmental redox status. Subsequent redox change
      experiments using recombinant proteins confirm the non-redox regulation of this
      protein. Detailed structural analysis shows that a difference in the conformation
      of the connecting loop (beta15-beta16) causes the formation of a water molecule
      mediated hydrogen bond network between the connecting loop and the catalytic loop
      in EcSSADH, making the catalytic loop of EcSSADH more rigid compared to that of
      human SSADH. The cytosolic localization of EcSSADH and the cellular function of
      the GABA shunt in E. coli might result in the non-redox mediated regulatory
      mechanisms of the protein.

PMID- 20060384
TI  - A potential role for Helicobacter pylori heat shock protein 60 in gastric
      tumorigenesis.
AB  - Helicobacter pylori has been found to promote the malignant process leading to
      gastric cancer. Heat shock protein 60 of H. pylori (HpHSP60) was previously been
      identified as a potent immunogene. This study investigates the role of HpHSP60 in
      gastric cancer carcinogenesis. The effect of HpHSP60 on cell proliferation, anti
      death activity, angiogenesis and cell migration were explored. The results showed
      that HpHSP60 enhanced migration by gastric cancer cells and promoted tube
      formation by umbilical vein endothelial cells (HUVECs); however, HpHSP60 did not
      increase cell proliferation nor was this protein able to rescue gastric cancer
      cells from death. Moreover, the results also indicated HpHSP60 had different
      effects on AGS gastric cancer cells or THP-1 monocytic cells in terms of their
      expression of pro-inflammatory cytokines, which are known to be important to
      cancer development. We propose that HpHSP60 may trigger the initiation of
      carcinogenesis by inducing pro-inflammatory cytokine release and by promoting
      angiogenesis and metastasis. Thus, this extracellular pathogen-derived HSP60 is
      potentially a vigorous virulence factor that can act as a carcinogen during
      gastric tumorigenesis.

PMID- 20060386
TI  - Performance characteristics of three random access cyclic citrullinated peptide
      antibody assays.
AB  - BACKGROUND: Cyclic citrullinated peptide antibodies (CCP Ab) are useful
      biomarkers for the early detection and diagnosis of rheumatoid arthritis (RA).
      METHODS: We evaluated the performance of 3 random access 2nd generation CCP Ab
      assays, the Abbott AxSYM and Architect analyzers and the Roche Modular Analytics
      E170 analyzer, for limit of detection (LOD), imprecision, results for samples
      from healthy subjects, analytic concordance, and interferences. Method comparison
      testing was performed using the AxSYM analyzer as the comparison method and a 3rd
      generation INOVA Quanta Lite ELISA assay was included. RESULTS: LOD
      determinations met the manufacturers' claims. Total CVs ranged from 1.6% to 8.2%.
      Results from healthy subjects were generally much lower than the manufacturers'
      decision cutoffs. Comparison to the AxSYM assay resulted in overall concordance
      ranging from 82.1% to 98.3%. These assays were resistant to interference from
      hemolysis, icterus, lipemia and rheumatoid factor. CONCLUSION: All 3 random
      access CCP Ab assays performed according to the manufacturers' claims and have
      the potential to improve workflow in clinical laboratories.

PMID- 20060385
TI  - Proton pump inhibitor lansoprazole is a nuclear liver X receptor agonist.
AB  - The liver X receptors (LXRalpha and LXRbeta) are transcription factors that
      control the expression of genes primarily involved in cholesterol metabolism. In
      the brain, in addition to normal neuronal function, cholesterol metabolism is
      important for APP proteolytic cleavage, secretase activities, Abeta aggregation
      and clearance. Particularly significant in this respect is LXR mediated
      transcriptional control of APOE, which is the only proven risk factor for late
      onset Alzheimer's disease. Using a transactivation reporter assay for screening
      pharmacologically active compounds and off patent drugs we identified the proton
      pump inhibitor Lansoprazole as an LXR agonist. In secondary screens and counter
      screening assays, it was confirmed that Lansoprazole directly activates LXR,
      increases the expression of LXR target genes in brain-derived human cell lines,
      and increases Abca1 and Apo-E protein levels in primary astrocytes derived from
      wild type but not LXRalpha/beta double knockout mice. Other PPIs activate LXR as
      well, but the efficiency of activation depends on their structural similarities
      to Lansoprazole. The identification of a widely used drug with LXR agonist-like
      activity opens the possibility for systematic preclinical testing in at least two
      diseases--Alzheimer's disease and atherosclerosis.

PMID- 20060388
TI  - VWF pseudogene: Mimics, masks and spoils.

PMID- 20060387
TI  - Association of estrogen receptor-alpha gene polymorphisms with cardiac autonomic
      nervous activity in healthy young Japanese males.
AB  - BACKGROUND: Estrogens exert beneficial effects on the cardiovascular system that
      are mediated by estrogen receptors. We examined the association between the
      estrogen receptor alpha gene (ESR1) PvuII and XbaI polymorphisms and cardiac
      autonomic nervous function in Japanese males. METHODS: We examined 252 young
      healthy males for association of ESR1 PvuII and XbaI polymorphisms and short-term
      heart rate variability (HRV) during supine rest and in a standing position. The
      very low frequency (VLF), low frequency (LF), and high frequency (HF) components
      of HRV were quantified by frequency domain analysis. RESULTS: Carriers of the
      ESR1 PvuII C allele had higher mean blood pressure (BP), while the XbaI GG
      genotype was significantly associated with higher diastolic and mean BP, but
      lower HR. In the haplotype analysis, carriers of the ESR1 haplotype 2 (PvuII C
      and XbaI A) allele had a higher systolic and mean BP, and lower HRV spectral
      powers (total power, VLF, LF, and HF components) in a supine rest compared with
      those of non-carriers. CONCLUSIONS: The ESR1 PvuII and XbaI haplotype is
      associated with BP variation and the reduction in cardiac autonomic nervous
      activity in young Japanese males, which may be precursors of future pathological
      episodes of cardiovascular diseases.

PMID- 20060389
TI  - Regulation of cholesterol homeostasis by liver X receptors.
AB  - Cellular cholesterol levels reflect a balance between uptake, efflux, and
      endogenous synthesis. The sterol-responsive transcription factors liver X
      receptors (LXRalpha and LXRbeta) help maintain cholesterol homeostasis, not only
      through promotion of cholesterol efflux from peripheral tissues but also through
      suppression of de novo synthesis and exogenous cholesterol uptake. In this
      review, we summarize the important role of LXRs in regulating expression of key
      members that keep cholesterol levels in balance.

PMID- 20060390
TI  - Measurement of oxidized lipoprotein (a) in patients with acute coronary syndromes
      and stable coronary artery disease by 2 ELISAs: using different capture antibody
      against oxidized lipoprotein (a) or oxidized LDL.
AB  - OBJECTIVE: To evaluate clinical value of oxidized lipoprotein(a) [ox-Lp(a)]
      levels. DESIGN AND METHODS: Ox-Lp(a) were measured by 2 ELISAs using antibodies
      against ox-Lp(a) [ox-Lp(a)1] or oxidized low-density lipoprotein [ox-Lp(a)2], and
      studied in 161 acute coronary syndromes (ACS) patients, 114 stable coronary
      artery disease (CAD) and 100 control subjects. RESULTS: Ox-Lp(a)1 was found
      related with ox-Lp(a)2 (r=0.864, P=0.000). Controlling for plasma lipids, Lp(a)
      and clinical characteristics, odds ratios of ox-Lp(a)1 on ACS and stable CAD were
      5.06 (95% confidence interval 1.82-14.04) and 2.20 (0.78-6.22); those of ox
      Lp(a)2 were 3.37 (1.07-10.63) and 1.35 (0.41-4.48), respectively. Receiver
      operating characteristic curve analysis confirmed that performances of ox-Lp(a)1
      were significantly superior to those for ox-Lp(a)2 in ACS (area: 0.803 vs. 0.723,
      P<0.001) and stable CAD (area: 0.670 vs. 0.607, P<0.01). CONCLUSION: Ox-Lp(a)
      levels using antibodies against ox-Lp(a) may represent a better risk marker than
      those using antibodies against oxidized low-density lipoprotein for ACS and
      stable CAD.

PMID- 20060391
TI  - Tracking diffusion of GM1 gangliosides and zona pellucida binding molecules in
      sperm plasma membranes following cholesterol efflux.
AB  - The molecules on mammalian spermatozoa that mediate recognition and binding to
      the zona pellucida of the egg are still not understood. Current concepts favour
      their assembly into multimolecular complexes in the plasma membrane in response
      to cholesterol efflux, an important step during sperm capacitation. Here, we
      track in real time diffusion of cross-linked clusters containing zona-binding
      molecules and GM1 gangliosides in the plasma membrane of live boar spermatozoa
      before and after cholesterol reduction. Both GM1 gangliosides and zona-binding
      molecules partition into a low density Triton X100 resistant phase suggesting
      their association with lipid rafts. Initially, GM1 and zona-binding molecules
      localize to the apical ridge on the acrosome but following cholesterol efflux
      with methyl-beta-cyclodextrin, clusters containing zona-binding molecules diffuse
      randomly over the acrosomal domain. Diffusing clusters of either type do not
      access the postacrosome. Spermatozoa agglutinated head-to-head show contact
      induced coalescence of GM1 gangliosides (but not zona-binding molecules)
      suggestive of a specific mechanosensitive response. Thus, cholesterol efflux
      initiates diffusion (and possibly formation) of novel lipid raft-like structures
      containing zona-binding molecules over the sperm acrosome. We hypothesise that in
      combination with contact coalescence, these mechanisms concentrate important
      molecules to the appropriate site on the sperm surface to mediate zona binding.

PMID- 20060392
TI  - Rap1, a mercenary among the Ras-like GTPases.
AB  - The small Ras-like GTPase Rap1 is an evolutionary conserved protein that
      originally gained interest because of its capacity to revert the morphological
      phenotype of Ras-transformed fibroblasts. Rap1 is regulated by a large number of
      stimuli that include growth factors and cytokines, but also physical force and
      osmotic stress. Downstream of Rap1, a plethora of effector molecules has been
      proposed on the basis of biochemical studies. Here, we present an overview of
      genetic studies on Rap1 in various model organisms and relate the observed
      phenotypes to in vitro studies. The picture that emerges is one in which Rap1 is
      a versatile regulator of morphogenesis, by regulating diverse processes that
      include establishment of cellular polarity, cell-matrix interactions and cell
      cell adhesion. Surprisingly, genetic experiments indicate that in the various
      model organisms, Rap1 uses distinct effector molecules that impinge upon the
      actin cytoskeleton and adhesion molecules.

PMID- 20060394
TI  - Spatial and temporal factors affecting parasite genotypes encountered by hosts:
      empirical data from American dog ticks (Dermacentor variabilis) parasitising
      raccoons (Procyon lotor).
AB  - The American dog tick (Dermacentor variabilis) is an important vector of numerous
      pathogens of humans and animals. In this study, we analysed population genetic
      patterns in D. variabilis at scales of the host individual (infrapopulation) and
      population (component population) to elucidate fine-scale spatial and temporal
      factors influencing transmission dynamics. We genotyped D. variabilis collected
      from raccoons (Procyon lotor) trapped in two habitat patches (located in Indiana,
      USA) which were spatially proximate (5.9 km) and limited in size (10.48 Ha and
      25.47 Ha, respectively). Despite the fine spatial sampling scale, our analyses
      revealed significant genetic differentiation amongst component populations and
      infrapopulations (within each component population), indicating a non-random
      pattern of encountering tick genotypes by raccoons at both scales evaluated. We
      found evidence for male-biased dispersal in the ticks themselves (in one
      component population) and an age-bias in spatial scales at which raccoons
      encountered ticks in the environment. At the scale of the component population,
      our analyses revealed that raccoons encountered ticks from a limited number of D.
      variabilis family groups, likely due to high reproductive variance amongst
      individual ticks. Finally, we found evidence for a temporal effect with raccoons
      encountering ticks in the environment as "clumps" of related individuals. While
      the genetic structure of parasite populations are increasingly being investigated
      at small spatial scales (e.g. the infrapopulation), our data reveal that genetic
      structuring can originate at scales below that of the infrapopulation, due to the
      interaction between temporal and biological factors affecting the encounter of
      parasites by individual hosts. Ultimately, our data indicate that genetic
      structure in parasites must be viewed as a consequence of both spatial and
      temporal variance in host-parasite interactions, which in turn are driven by
      demographic factors related to both the host and parasite.

PMID- 20060393
TI  - Regulation of photoreceptor gene expression by the retinal homeobox (Rx) gene
      product.
AB  - The retinal homeobox (Rx) gene product is essential for eye development. However
      little is known about its molecular function. It has been demonstrated that Rx
      binds to photoreceptor conserved element (PCE-1), a highly conserved element
      found in the promoter region of photoreceptor-specific genes such as rhodopsin
      and red cone opsin. We verify that Rx is co-expressed with rhodopsin and red cone
      opsin in maturing photoreceptors and demonstrate that Rx binds to the rhodopsin
      and red cone opsin promoters in vivo. We also find that Rx can cooperate with the
      Xenopus analogs of Crx and Nrl, otx5b and XLMaf (respectively), to activate a
      Xenopus opsin promoter-dependent reporter. Finally, we demonstrate that reduction
      of Rx expression in tadpoles results in decreases in expression of several PCE-1
      containing photoreceptor genes, abnormal photoreceptor morphology, and impaired
      vision. Our data suggests that Rx, in combination with other transcription
      factors, is necessary for normal photoreceptor gene expression, maintenance, and
      function. This establishes a direct role for Rx in regulation of genes expressed
      in a differentiated cell type.

PMID- 20060395
TI  - Neospora caninum excreted/secreted antigens trigger CC-chemokine receptor 5
      dependent cell migration.
AB  - Neospora caninum, the causative agent of neosporosis, is an obligate
      intracellular parasite considered to be a major cause of abortion in cattle
      throughout the world. Most studies concerning N. caninum have focused on life
      cycle, seroepidemiology, pathology and vaccination, while data on host-parasite
      interaction, such as host cell migration, mechanisms of evasion and dissemination
      of this parasite during the early phase of infection are still poorly understood.
      Here we show the ability of excreted/secreted antigens from N. caninum (NcESAs)
      to attract monocytic cells to the site of primary infection in both in vitro and
      in vivo assays. Molecules from the family of cyclophilins present on the NcESAs
      were shown to work as chemokine-like proteins and NcESA-induced chemoattraction
      involved G(i) protein signaling and participation of CC-chemokine receptor 5
      (CCR5). Additionally, we demonstrate the ability of NcESAs to enhance the
      expression of CCR5 on monocytic cells and this increase occurred in parallel with
      the chemotactic activity of NcESAs by increasing cell migration. These results
      suggest that during the first days of infection, N. caninum produces molecules
      capable of inducing monocytic cell migration to the sites of infection, which
      will consequently enhance initial parasite invasion and proliferation.
      Altogether, these results help to clarify some key features involved in the
      process of cell migration and may reveal virulence factors and therapeutic
      targets to control neosporosis.

PMID- 20060396
TI  - Comparative virulence of Beauveria bassiana isolates against lepidopteran pests
      of vegetable crops.
AB  - Forty-three isolates of the entomopathogenic fungus Beauveria bassiana were
      screened for virulence against second-instar larvae of diamondback moth (Plutella
      xylostella) (DBM), European corn borer (Ostrinia nubilalis) (ECB), corn earworm
      (Helicoverpa zea) (CEW), and fall armyworm (Spodoptera frugiperda) (FAW); 30 of
      these isolates were tested against beet armyworm (Spodoptera exigua) (BAW).
      Highly virulent isolates were also tested against black cutworm (Agrotis ipsilon)
      (BCW), and the most virulent isolate was also assayed against imported cabbage
      worm (Pieris rapae) (ICW) and cabbage looper (Trichoplusia ni) (CL). All
      lepidopteran species tested were susceptible to B. bassiana. Corn earworm and
      beet armyworm were most susceptible to fungal infection, and fall armyworm was
      least susceptible. Limited testing suggested low susceptibility of black cutworm
      and cabbage looper. B. bassiana isolate 1200 exhibited virulence against all pest
      species greater than or equal to commercial strain GHA of B. bassiana currently
      registered in the USA as BotaniGard. In assays in which larvae were topically
      sprayed and maintained on the treated substrate for 24h at 100% relative
      humidity, 6-day (25 degrees C) median lethal concentrations (LC(50)s) of this
      isolate against CEW, BAW, DBM, FAW, ICW, ECB, CL, and BCW were 4, 5, 7, 11, 12,
      98, 125, and 273 conidia/mm(2), respectively. The respective LC(50)s of
      commercial strain GHA against these pest species were 9, 67, 97, 1213, 29, 1668,
      541, and 3504 conidia/mm(2). Use of LC(50) versus median lethal concentration
      ratios (comparing LC(50)s of each isolate to a "standard" strain) generated
      similar rankings of isolate virulence. Results from parametric ANOVAs of log
      LC(50) values followed by Tukey HSD multiple comparisons tests and those from
      Kruskal-Wallis nonparametric analyses followed by sequential Bonferroni tests for
      means comparisons were nearly identical.

PMID- 20060397
TI  - Efficacy of olmesartan and nifedipine on recurrent hypoxia-induced left
      ventricular remodeling in diabetic mice.
AB  - AIMS: Recurrent hypoxia due to sleep apnea syndrome is implicated in
      cardiovascular events, especially in diabetic patients, but the underlying
      mechanisms remain controversial. We previously reported that angiotensin II
      receptor blockers can improve hypoxia-induced left ventricular remodeling. The
      aim of this study was to examine the effect on left ventricular remodeling of
      adding a calcium channel blocker to angiotensin II receptor blocker therapy in
      diabetic mice exposed to recurrent hypoxia. MAIN METHODS: Male db/db mice (8-week
      old) and age-matched control db/+ mice were fed a Western diet and subjected to
      recurrent hypoxia (oxygen at 10+/-0.5% for 8h daily during the daytime) or
      normoxia for 3weeks. Hypoxic db/db mice were treated with the vehicle, olmesartan
      (3mg/kg/day), nifedipine (10mg/kg/day), or both drugs. KEY FINDINGS: Recurrent
      hypoxia caused hypertrophy of cardiomyocytes, interstitial fibrosis, and a
      significant increase in expression of the oxidative stress marker 4-hydroxy-2
      nonenal (4-HNE) in the left ventricular myocardium. Treatment with olmesartan,
      nifedipine, or both drugs had no effect on systolic blood pressure, and each
      treatment achieved similar suppression of 4-HNE expression. Olmesartan and the
      combination with olmesartan and nifedipine significantly prevented cardiomyocyte
      hypertrophy more than treatment with nifedipine alone. On the other hand,
      olmesartan combined with nifedipine significantly reduced cytokine expression,
      superoxide production and matrix metalloproteinase (MMP)-9 activity, and
      significantly suppressed interstitial fibrosis in the left ventricular
      myocardium. SIGNIFICANCE: The combination with olmesartan and nifedipine, as well
      as a monotherapy with olmesartan, exerts preferable cardioprotection in diabetic
      mice exposed to recurrent hypoxia.

PMID- 20060398
TI  - Complicated biallelic inactivation of Pten in radiation-induced mouse thymic
      lymphomas.
AB  - Inactivation of the phosphatase and tensin homolog gene (Pten) occurs via
      multiple tissue-dependent mechanisms including epigenetic silencing, point
      mutations, insertions, and deletions. Although frequent loss of heterozygosity
      around the Pten locus and plausible involvement of epigenetic silencing have been
      reported in radiation-induced thymic lymphomas, the proportion of lymphomas with
      inactivated Pten and the spectrum of causal aberrations have not been extensively
      characterized. Here, we assessed the mode of Pten inactivation by comprehensive
      analysis of the expression and alteration of Pten in 23 radiation-induced thymic
      lymphomas developed in B6C3F1 mice. We found no evidence for methylation
      associated silencing of Pten; rather, complex structural abnormalities comprised
      of missense and nonsense mutations, 1- and 3-bp insertions, and focal deletions
      were identified in 8 of 23 lymphomas (35%). Sequencing of deletion breakpoints
      suggested that aberrant V(D)J recombination and microhomology-mediated
      rearrangement were responsible for the focal deletions. Seven of the 8 lymphomas
      had biallelic alterations, and 4 of them did not express Pten protein. These Pten
      aberrations coincided with downstream Akt phosphorylation. In conclusion, we
      demonstrate that Pten inactivation is frequently biallelic and is caused by a
      variety of structural abnormalities (rather than by epigenetic silencing) and is
      involved in radiation-induced lymphomagenesis.

PMID- 20060399
TI  - ATR preferentially interacts with common fragile site FRA3B and the binding
      requires its kinase activity in response to aphidicolin treatment.
AB  - The instability of common fragile sites (CFSs) contributes to the development of
      a variety of cancers. The ATR-dependent DNA damage checkpoint pathway has been
      implicated in maintaining CFS stability, but the mechanism is incompletely
      understood. The goal of our study was to elucidate the action of the ATR protein
      in the CFS-specific ATR-dependent checkpoint response. Using a chromatin
      immunoprecipitation assay, we demonstrated that ATR protein preferentially binds
      (directly or through complexes) to fragile site FRA3B as compared to non-fragile
      site regions, under conditions of mild replication stress. Interestingly, the
      amount of ATR protein that bound to three regions of FRA3B peaked at 0.4microM
      aphidicolin (APH) treatment and decreased again at higher concentrations of APH.
      The total amounts of cellular ATR and several ATR-interacting proteins remained
      unchanged, suggesting that ATR binding to the fragile site is guided initially by
      the level of replication stress signals generated at FRA3B due to APH treatment
      and then sequestered from FRA3B regions by successive signals from other non
      fragile site regions, which are produced at the higher concentrations of APH.
      This decrease in ATR binding to fragile site FRA3B at the higher concentrations
      of APH may account for the increasing number of chromosome gaps and breaks
      observed under the same conditions. Furthermore, inhibition of ATR kinase
      activity by treatment with 2-aminopurine (2-AP) or by over-expression of a kinase
      dead ATR mutant showed that the kinase activity is required for the binding of
      ATR to fragile DNAs in response to APH treatment. Our results provide novel
      insight into the mechanism for the regulation of fragile site stability by ATR.

PMID- 20060400
TI  - A quantitative analysis of genomic instability in lymphoid and plasma cell
      neoplasms based on the PIG-A gene.
AB  - It has been proposed that hypermutability is necessary to account for the high
      frequency of mutations in cancer. However, historically, the mutation rate (mu)
      has been difficult to measure directly, and increased cell turnover or selection
      could provide an alternative explanation. We recently developed an assay for mu
      using PIG-A as a sentinel gene and estimated that its average value is 10.6 x 10(
      7) mutations per cell division in B-lymphoblastoid cell lines (BLCLs) from normal
      donors. Here we have measured mu in human malignancies and found that it was
      elevated in cell lines derived from T cell acute lymphoblastic leukemia, mantle
      cell lymphoma, follicular lymphoma in transformed phase, and 2 plasma cell
      neoplasms. In contrast, mu was much lower in a marginal zone lymphoma cell line
      and 5 other plasma cell neoplasms. The highest mu value that we measured, 3286 x
      10(-7), is 2 orders of magnitude above the range we have observed in non
      malignant human cells. We conclude that the type of genomic instability detected
      in this assay is a common but not universal feature of hematologic malignancies.

PMID- 20060401
TI  - Imitation of para-phonological detail following left hemisphere lesions.
AB  - Imitation in speech refers to the unintentional transfer of phonologically
      irrelevant acoustic-phonetic information of auditory input into speech motor
      output. Evidence for such imitation effects has been explained within the
      framework of episodic theories. However, it is largely unclear, which neural
      structures mediate speech imitation and how imitation is related with verbal
      repetition. Two experiments were conducted, a standard repetition task, and a
      transformation task requiring phonetic manipulation of the presented auditory
      nonword stimuli. Nonword materials varied sub-phonemically in word stress (pitch
      elevation magnitude; PEM) and in a parameter related to speaking style, i.e., the
      explicitness of final schwa-syllables (SSE). We examined speech imitation in 10
      healthy participants, 10 patients with phonological impairments after left
      hemisphere lesions, and 11 patients with right hemisphere lesions. In repetition,
      significant imitation of SSE and PEM was observed in all groups of participants.
      In transformation, imitation occurred in healthy participants and in the patients
      with right hemisphere lesions, whereas no imitation was observed in the patient
      group with left hemisphere lesions. Voxel-based lesion-symptom mapping revealed
      that different areas within the left temporal plane influenced the degree of
      imitation of phonetic and prosodic detail in repetition.

PMID- 20060402
TI  - Reflecting upon line bisection: mirror reversal increases the magnitude of
      pseudoneglect.
AB  - In order to investigate the effect of congruent and non-congruent motor actions
      upon pseudoneglect, 'real' lines and mirror reversed 'virtual' lines were
      bisected in left and right hemispaces by 50 right handed subjects, 25 males, 25
      females, with both left and right hands. Statistical analysis revealed
      significantly greater pseudoneglect for the non-congruent motor condition
      (virtual > real), hand (left > right), gender (male > female) and hemispace for
      virtual lines (left > right). These results are explained in terms of the
      interaction between three factors whose influence can jointly and severally
      result in pseudoneglect: right hemisphere specialization for spatial attention,
      right hemisphere activation resulting from hand use and sensorimotor
      discrepancies and the allocation of visual attention.

PMID- 20060403
TI  - Estrogen and oxidative stress: A novel mechanism that may increase the risk for
      cardiovascular disease in women.
AB  - Although early studies demonstrated that exogenous estrogen lowered a woman's
      risk of cardiovascular disease, recent trials indicate that HRT actually
      increases the risk of coronary heart disease or stroke. However, there is no
      clear explanation for this discrepancy. Is estrogen a helpful or a harmful
      hormone in terms of cardiovascular function? This review discusses some recent
      findings that propose a novel mechanism which may shed significant light upon
      this controversy. We propose that nitric oxide synthase (NOS) expressed within
      the vascular wall is a target of estrogen action. Under normal conditions in
      younger women, the primary product of estrogen action is NO, which produces a
      number of beneficial effects on vascular biology. As a woman ages, however, there
      is evidence for loss of important molecules essential for NO production (e.g.,
      tetrahydrobiopterin, l-arginine). As these molecules are depleted, NOS becomes
      increasingly "uncoupled" from NO production, and instead produces superoxide, a
      dangerous reactive oxygen species. We propose that a similar uncoupling and
      reversal of estrogen response occurs in diabetes. Therefore, we propose that
      estrogen is neither "good" nor "bad", but simply stimulates NOS activity. It is
      the biochemical environment around NOS that will determine whether estrogen
      produces a beneficial (NO) or deleterious (superoxide) product, and can account
      for this dual and opposite nature of estrogen pharmacology. Further, this
      molecular mechanism is consistent with recent analyses revealing that HRT
      produces salutary effects in younger women, but mainly increases the risk of
      cardiovascular dysfunction in older postmenopausal women.

PMID- 20060405
TI  - Sustained pupillary constrictions mediated by an L- and M-cone opponent process.
AB  - We show that irradiance-coding alone cannot explain the sustained pupillary
      constrictions evoked by chromatic and luminance variations in a stimulus. For
      example, stimulus modulations that decremented the contrasts in L- and M-cones as
      well as rods and melanopsin photoreceptors produced sustained constrictions
      rather than the predicted dilations. Although the sustained responses are
      unidirectional, we confirm that they are at least partially mediated by an L- and
      M-cone opponent interaction. We discuss the implications of sustained
      unidirectional chromatic responses in view of the function of the pupil to
      improve the clarity of vision.

PMID- 20060404
TI  - Biochemical profile of dogs experimentally envenomed with Tityus serrulatus
      scorpion venom.
AB  - The aim of this study was to evaluate the canine blood and urinary profiles after
      envenomation by Tityus serrulatus venom. Twelve dogs were randomly distributed
      into two equal groups. Control group animals received 0.5 mL phosphate buffered
      saline (PBS) injected subcutaneously into the internal portion of the left thigh,
      whilst dogs in the envenomed group were injected with scorpion venom (250
      microg/kg in 0.5 mL PBS). No significant alterations were detected in the urine
      of envenomed dogs. Levels of plasma glucose and serum urea, creatinine, total
      protein, potassium, alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), creatine kinase (CK), lactate dehydrogenase (LDH), and amylase were
      determined. Semi-quantitative analysis of serum cardiac troponin I (cTnI) was
      performed using an immunochromatographic test. The concentrations of cortisol and
      insulin were determined using commercial radioimmunoassay kits. Increases in
      serum cortisol levels in experimental group animals coincided with hyperglycaemia
      and was probably a response to pain. Increased insulin levels were observed
      during the hyperglycaemic peaks. Envenomed dogs presented discreet increases in
      ALT, AST and CK, but no alterations in LDH, amylase, cTnI, urea, creatinine and
      potassium levels were observed. It was concluded that the venom of T. serrulatus
      induces blood and urinary biochemical changes in dogs.

PMID- 20060406
TI  - Changes in area affect figure-ground assignment in pigeons.
AB  - A critical cue for figure-ground assignment in humans is area: smaller regions
      are more likely to be perceived as figures than are larger regions. To see if
      pigeons are similarly sensitive to this cue, we trained birds to report whether a
      target appeared on a colored figure or on a differently colored background. The
      initial training figure was either smaller than (Experiments 1 and 2) or the same
      area as (Experiment 2) the background. After training, we increased or decreased
      the size of the figure. When the original training shape was smaller than the
      background, pigeons' performance improved with smaller figures (and worsened with
      larger figures); when the original training shape was the same area as the
      background, pigeons' performance worsened when they were tested with smaller
      figures. A smaller figural region appeared to improve the figure-ground
      discrimination only when size was a relevant cue in the initial discrimination.

PMID- 20060407
TI  - Novel sulfation of curdlan assisted by ultrasonication.
AB  - This study carried out a novel sulfation process on curdlan. Results document
      that sulfation of the polysaccharide was more effective with the assistance of
      ultrasonication. Ultrasonication significantly increased the DS value of samples
      by almost fourfold (from about 0.030 to 0.115). Evaluation of the extent of
      sulfation has been made using FTIR, (1)H NMR, (13)C NMR and SEC. Both FTIR and
      (1)H NMR spectra confirmed the occurrence of sulfation. The combined effect of
      ultrasonication and acid resulted in relatively small molecular weights (e.g.,
      sample 360_360: MW approximately 49.0 kDa), as opposed to curdlan (MW
      approximately 807 kDa). This work contributes to better understanding of the
      molecular mechanism governing the sonochemical processes of polysaccharide
      modification with improved physicochemical properties, and potential biomedical
      application.

PMID- 20060408
TI  - DnaK/DnaJ/GrpE of Hsp70 system have differing effects on alpha-synuclein
      fibrillation involved in Parkinson's disease.
AB  - Chaperones assist in maintenance of functional proteome in vivo. However, they
      seem to be either ineffective or overwhelmed in the case of protein misfolding
      diseases like Parkinson's, Huntington's or Alzheimer's. Studies involving one or
      two chaperones from Hsp70 system cannot provide comprehensive information about
      the involvement of whole system. We present for the first time, in vitro
      characterization of the effect of each component of Hsp70 system on alpha
      synuclein (involved in Parkinson's) using SEC and ThT assay. Our results show
      while some components enhance the aggregation others seem to stabilize alpha
      synuclein against aggregation. Keeping whole Hsp70 system intact, the factor
      responsible for triggering aggregation seemed to be initial alpha-synuclein
      conformation.

PMID- 20060409
TI  - Influence of extraction conditions on properties of seed xyloglucan.
AB  - Xyloglucans are water-soluble polysaccharides that serve as storage in
      cotyledonary tissues from seeds of Hymenaea courbaril among other Leguminosae.
      The use of xyloglucans is dependent on their solution properties. We now examine
      the influence of different times of extractions on its properties. Xyloglucans
      were obtained from milled and defatted cotyledons of H. courbaril by aqueous
      extraction at 25 degrees C for 0.25, 0.5, 1, 5, 15, 24, and 48 h. Composition
      data showed that increase in time lead to the increased protein contamination and
      arabinose content. Xyloglucans obtained with longer times of extraction had an
      average molar mass greater than those obtained with shorter times. The
      hydrodynamic radius and the radius of gyration also increased with the increase
      in the time of extraction. The ratio R(g)/R(h) was calculated and the values
      decreased slightly for increasing times of extraction. The effect of time also
      affected the viscosity which increased with the increase in time of extraction,
      and the longer ones probably contributing to the aggregation of xyloglucans.

PMID- 20060411
TI  - BIR2 domain of XIAP plays a marginal role in inhibition of executioner caspases.
AB  - The ability of the irreversibly denatured XIAP-BIR2 domain versus the native
      protein in inhibition of executioner caspase-3 and -7 was investigated. The
      denatured protein that lacked the physical characteristics of the native protein
      inhibited caspase-7, while failing to inhibit caspase-3. Furthermore, the
      kinetics of association of the denatured protein with caspase-7 decreased
      substantially suggesting that the exposure of the linker is reduced. This was
      further confirmed by the decreased level of proteolysis at the linker by trypsin
      for the denatured protein. These results suggest that the essential moiety of the
      XIAP involved in inhibition is the linker joining BIR1 to BIR2 and that the BIR2
      plays a marginal role in inhibition.

PMID- 20060410
TI  - Characterization of a novel oligomeric SGNH-arylesterase from Sinorhizobium
      meliloti 1021.
AB  - A novel oligomeric SGNH-arylesterase (Sm23) from Sinorhizobium meliloti 1021 was
      characterized using biochemical and biophysical methods. A sequence comparison of
      Sm23 with other SGNH members confirmed the presence of catalytic triad (Ser(10),
      Asp(187), and His(190)) and oxyanion holes (Ser(10)-Gly(50)-Asn(90)). The wild
      type enzyme was able to hydrolyze p-nitrophenyl acetate, alpha- and beta-naphthyl
      acetate, while S10A mutant completely lost its activity. Structural properties of
      Sm23 were investigated using circular dichroism (CD), fluorescence, dynamic light
      scattering (DLS), chemical cross-linking, electron microscopy (EM), and time of
      flight (TOF) mass spectrometry. Furthermore, spherical or globular aggregates
      were observed with 1-butyl-3-methylimidazolium tetrafluoroborate, while amorphous
      aggregates were formed with 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide.

PMID- 20060412
TI  - Vibrational dynamics of poly(L-isoleucine).
AB  - Normal mode analysis and their dispersion for poly(L-isoleucine) are reported by
      using Urey Bradley force field and Fourier transform IR. The calculated
      frequencies are found to be in reasonably good agreement with the Fourier
      transform IRspectra. Experimental measurements reported by Wunderlich et al. also
      support the calculated specific heat variation of poly(L-isoleucine).

PMID- 20060413
TI  - Designing of silver nanoparticles in gum arabic based semi-IPN hydrogel.
AB  - Semi-interpenetrating network (SISH-GA) composed of gum arabic and crosslinked
      copolymer of poly(2-hydroxyethyl methacrylate-co-acrylic acid) was synthesized in
      the presence of initiator ammonium persulfate (APS), crosslinker N,N'-methylene
      bis acrylamide (MBA), catalyzed by [CuSO4/glycine] chelate complex and finally
      loaded nanoparticle inside the networks via in situ reduction of silver nitrate
      (AgNO3) using trisodium citrate (Na3C6H5O7) as reducing agent. Characterization
      of the product was performed along with its degradability in Escherichia coli
      medium.

PMID- 20060414
TI  - 2,2,2-Trifluroethanol induces simultaneous increase in alpha-helicity and
      aggregation in alkaline unfolded state of bovine serum albumin.
AB  - Little work has been done to understand the folding of proteins at alkaline
      conditions. BSA acquires a partially reversible unfolded state at pH 13.0, devoid
      of any native structure. Introduction of methanol, ethanol and 2-propanol with
      the alkaline unfolded protein resulted in beta-sheet-like structure formation,
      and 2,2,2-trifluroethanol found to enhance alpha-helical conformations with
      simultaneous increase in aggregation. The extent of secondary and tertiary
      structure formation is in the order of methanol < ethanol < 2-propanol < 2,2,2
      trifluroethanol. Exposure of hydrophobic core of protein molecules in apolar
      environment of 2,2,2-trifluroethanol seems to promote intermolecular cluster
      formation. This is one of the very few reports that alpha-helical structures can
      also aggregate.

PMID- 20060415
TI  - Identification and characterization of matrix metalloproteinase-13 sequence
      structure and expression during embryogenesis and infection in channel catfish
      (Ictalurus punctatus).
AB  - Matrix metalloproteinase-13 (MMP-13), referred to as collagenase-3, is a
      proteolytic enzyme that plays a key role in degradation and remodelling of host
      extracellular matrix proteins. The objective of this study was to characterize
      the MMP-13 gene in channel catfish, and to determine its pattern of expression in
      various healthy tissues and during embryogenesis. Since MMP-13 has been shown to
      have importance in tissue remodelling and some pathological processes, we further
      studied its involvement in the defense responses of catfish after bacterial
      infection. The channel catfish MMP-13 cDNA contains an open reading frame of
      1416bp encoding 471 amino acids. Using RT-PCR analysis, MMP-13 was widely
      expressed in various health tissues. Using quantitative real-time PCR analysis,
      expression of MMP-13 gene was up-regulated by bacterial infection. During normal
      embryological development, MMP-13 expression was slightly increased in the first
      day post-fertilization and sharply up-regulated from 1-day post-fertilization
      through hatching.

PMID- 20060416
TI  - Genetic association studies of glutamate, GABA and related genes in schizophrenia
      and bipolar disorder: a decade of advance.
AB  - Schizophrenia (SZ) and bipolar disorder (BD) are debilitating neurobehavioural
      disorders likely influenced by genetic and non-genetic factors and which can be
      seen as complex disorders of synaptic neurotransmission. The glutamatergic and
      GABAergic neurotransmission systems have been implicated in both diseases and we
      have reviewed extensive literature over a decade for evidence to support the
      association of glutamate and GABA genes in SZ and BD. Candidate-gene based
      population and family association studies have implicated some ionotrophic
      glutamate receptor genes (GRIN1, GRIN2A, GRIN2B and GRIK3), metabotropic
      glutamate receptor genes (such as GRM3), the G72/G30 locus and GABAergic genes
      (e.g. GAD1 and GABRB2) in both illnesses to varying degrees, but further
      replication studies are needed to validate these results. There is at present no
      consensus on specific single nucleotide polymorphisms or haplotypes associated
      with the particular candidate gene loci in these illnesses. The genetic
      architecture of glutamate systems in bipolar disorder need to be better studied
      in view of recent data suggesting an overlap in the genetic aetiology of SZ and
      BD. There is a pressing need to integrate research platforms in genomics,
      epistatic models, proteomics, metabolomics, neuroimaging technology and
      translational studies in order to allow a more integrated understanding of
      glutamate and GABAergic signalling processes and aberrations in SZ and BD as well
      as their relationships with clinical presentations and treatment progress over
      time.

PMID- 20060417
TI  - Interaction of gamma-radiation and methyl mercury during a critical phase of
      neonatal brain development in mice exacerbates developmental neurobehavioural
      effects.
AB  - In our environment, mammals (including humans) are exposed to various types of
      ionizing radiation and both persistent and non-persistent toxic chemicals. It is
      known that ionizing radiation, as well as methyl mercury, can induce
      neurotoxicological and neurobehavioural effects in mammals. These developmental
      neurotoxic effects can be seen following exposure during gestation. There is a
      lack of knowledge concerning the effects and consequences of low-dose exposure
      during critical phases of perinatal and/or neonatal brain development, and of the
      combination of ionizing radiation and environmental chemicals. A recent study has
      indicated that low doses of ionizing radiation to the human brain during infancy
      influence cognitive ability in adulthood. In the present study, 10-day old
      neonatal male NMRI mice were exposed to a single oral dose of MeHg (0.40 or 4.0
      mg/kg bw). Four hours after the MeHg exposure the mice were subjected to (60)Co
      gamma-radiation on one occasion at doses of 0.2 and 0.5 Gy. The animals were then
      subjected to a spontaneous behaviour test at 2 and 4 months, and a water maze
      test at the age of 5 months. Neither the single dose of MeHg (0.4 mg/kg bw) nor
      the radiation dose of 0.2 Gy affected their spontaneous behaviour, whereas the co
      exposure to external gamma-radiation and MeHg caused developmental neurotoxic
      effects. The study shows that gamma-radiation and MeHg can interact and
      significantly exacerbate developmental neurotoxic effects, as manifested by
      disrupted spontaneous behaviour, lack of habituation, and impaired learning and
      memory functions.

PMID- 20060418
TI  - Folic acid and soybean isoflavone combined supplementation protects the post
      neural tube closure defects of rodents induced by cyclophosphamide in vivo and in
      vitro.
AB  - To evaluate the neuroprotective effect of folic acid (FA) and soybean isoflavone
      (SIF) combined supplementation on the post-neural tube closure of rodents induced
      by cyclophosphamide (CPA) in vitro and in vivo, pregnant rats were randomly
      divided into control, model, solo-FA intervention, solo-SIF intervention and co
      intervention of FA and SIF groups. Rats in solo-intervention groups and co
      intervention group were treated with FA 0.7 mg/kg, SIF 160 mg/kg and FA 0.7
      mg/kg+SIF 160 mg/kg at the duration of pregnancy, respectively. On the 13th day
      of gestation, control rats were given physiological saline and the other four
      groups were treated with CPA12.5mg/kg. On the 14th day of gestation, three rats
      selected randomly from every group were executed and the ultrastructure, DNA
      damage and the proteins expressions of Bcl-2, Bax and P53 on embryo brains were
      checked. The rest of the rats were executed on the 20th day, the frequency of
      neural tube closure defects and fetus' development indices were measured. In
      addition, T-SOD, MDA and NO in serum of the pregnant rats were checked. In vitro,
      the effect of FA and genistein on the apoptosis was determined. Compared with the
      model group, the malformation incidence was lower but fetus' development indices
      were higher in the combination treated group. The combination decreased the
      damage of CPA, such as damaged nuclear DNA, early apoptotic morphological
      changes, Bax and P53 expressions on embryo brains and in vivo. Furthermore, T-SOD
      activity in serum of the pregnant rats increased and the levels of MDA and NO
      decreased in the combined supplementation group. Our study indicates the
      neuroprotection of FA and SIF combined administration is superior to solo
      treatment. Decrease of DNA damage and neuron apoptosis involved in the
      mechanisms. Furthermore, the up-regulation of Bcl-2 and the down-regulation of
      Bax and P53 proteins also participate in the effect.

PMID- 20060419
TI  - Rho kinase inhibitor Y-27632 facilitates recovery from experimental peripheral
      neuropathy induced by anti-cancer drug cisplatin.
AB  - Chemotherapy drugs have neurotoxicity associated with treatment, which can become
      a dose-limiting problem when clinical presentation is severe. However, there is
      no effective therapy to circumvent the neurotoxicity of anti-cancer drug
      treatment. In this study, we utilized a newly designed mouse model of cisplatin
      induced peripheral neuropathy to determine both the severity of neurotoxicity
      induced by drug treatment and the effectiveness of the Rho kinase inhibitor Y
      27632 in post-treatment recovery. Sensory nerve conduction studies revealed a
      significant increase in mean distal (peak) latency with cisplatin treatment,
      indicating a deterioration of sensory nerve function. Also, hind paw touch
      sensitivity decreased steadily with increasing cumulative dose of cisplatin.
      Histological and immunohistochemical analyses of the sural nerve using neuronal
      marker protein gene product 9.5 (PGP 9.5) demonstrated abnormal nerve fiber
      morphology in cisplatin-treated mice. Remarkably, post-treatment with Y-27632
      improved the sural nerve distal (peak) latency and sensory threshold to return to
      pre-treatment levels. Sural nerve histology worsened in the absence of Y-27632
      during recovery. These studies suggest that Rho kinase inhibitor Y-27632 can
      initiate regeneration of damaged nerves following cisplatin treatment.

PMID- 20060420
TI  - Effective siRNAs inhibit the replication of novel influenza A (H1N1) virus.
AB  - In March and April 2009, an entirely novel influenza A (H1N1) virus (NIAV)
      emerged in Mexico and the USA. During the subsequent months, the virus rapidly
      spread all over the world by person-to-person transmission. In this report, RNA
      interference (RNAi) was used as an antiviral agent to inhibit NIAV replication in
      A549 cells. Ten small interfering RNAs (siRNAs) targeting extremely conserved
      regions among multiple NIAV genomes could effectively block the replication of
      NIAV strain A/Beijing/01/2009 (H1N1) in A549 cells. This study may be useful to
      confront the sudden emergence of NIAV infection.

PMID- 20060421
TI  - Strategies for development of Dengue virus inhibitors.
AB  - Antiviral drug discovery is becoming increasingly important due to the global
      threat of viral disease pandemics. Many members of the genus Flavivirus are
      significant human pathogens, among which dengue virus (DENV) alone poses a public
      health threat to 2.5 billion worldwide, leading to 50-100 million human
      infections each year. Neither vaccine nor effective therapeutics is currently
      available for DENV. Development of a DENV vaccine has been challenging, because
      of the need to simultaneously immunize and induce a long-lasting protection
      against all four serotypes of DENV; an incompletely immunized individual may be
      sensitized to life-threatening dengue hemorrhagic fever or dengue shock syndrome.
      The challenges associated with vaccine development have underscored the
      importance of development of antiviral therapies for DENV and other flaviviruses.
      Here we review the strategies to identify inhibitors for DENV therapy. Both viral
      and host proteins essential for viral replication cycle are potential targets for
      antiviral development. Inhibitors could be identified by multiple approaches,
      including enzyme-based screening, viral replication-based screening, structure
      based rational design, virtual screening, and fragment-based screening. The
      strategies discussed in this report should be applicable to antiviral development
      of other viruses.

PMID- 20060422
TI  - Cholinergic systems mediate action from movement to higher consciousness.
AB  - There is a fundamental link between cholinergic neurotransmitter function and
      overt and covert actions. Major cholinergic systems include peripheral motor
      neurons organizing skeletal muscle movements into overt behaviors and cholinergic
      neurons in the basal forebrain and mesopontine regions that mediate covert
      actions realized as states of consciousness, arousal, selective attention,
      perception, and memory. Cholinergic interneurons in the striatum appear to
      integrate conscious and unconscious actions. Neural network models involving
      cholinergic neurons, as well as neurons using other neurotransmitters, emphasize
      connective circuitry as being responsible for both motor programs and neural
      correlates of higher consciousness. This, however, is only a partial description.
      At a more fundamental level lie intracellular mechanisms involving the
      cytoskeleton, which are common to both muscle contraction and neuroplastic
      responses in targets of central cholinergic cells attendant with higher
      cognition. Acetylcholine, acting through nicotinic receptors, triggers
      interactions between cytoskeletal proteins in skeletal muscle cells, as has been
      long known. There is also evidence that acetylcholine released at central sites
      acts through muscarinic and nicotinic receptors to initiate responses in actin
      and microtubule proteins. These effects and their implications for cholinergic
      involvement in higher cognition are explored in this review.

PMID- 20060423
TI  - The cholinergic system, sigma-1 receptors and cognition.
AB  - This article provides an overview of present knowledge regarding the relationship
      between the cholinergic system and sigma-1 receptors, and discusses potential
      applications of sigma-1 receptor agonists in the treatment of memory deficits and
      cognitive disorders. Sigma-1 receptors, initially considered as a subtype of the
      opioid family, are unique ligand-regulated molecular chaperones in the
      endoplasmatic reticulum playing a modulatory role in intracellular calcium
      signaling and in the activity of several neurotransmitter systems, particularly
      the cholinergic and glutamatergic pathways. Several central nervous system (CNS)
      drugs show high to moderate affinities for sigma-1 receptors, including
      acetylcholinesterase inhibitors (donepezil), antipsychotics (haloperidol,
      rimcazole), selective serotonin reuptake inhibitors (fluvoxamine, sertraline) and
      monoamine oxidase inhibitors (clorgyline). These compounds can influence
      cognitive functions both via their primary targets and by activating sigma-1
      receptors in the CNS. Sigma-1 agonists show powerful anti-amnesic and
      neuroprotective effects in a large variety of animal models of cognitive
      dysfunction involving, among others (i) pharmacologic target blockade (with
      muscarinic or NMDA receptor antagonists or p-chloroamphetamine); (ii) selective
      lesioning of cholinergic neurons; (iii) CNS administration of beta-amyloid
      peptides; (iv) aging-induced memory loss, both in normal and senescent
      accelerated rodents; (v) neurodegeneration induced by toxic compounds (CO,
      trimethyltin, cocaine), and (vi) prenatal restraint stress.

PMID- 20060424
TI  - Systemic treatment with protein synthesis inhibitors attenuates the expression of
      cocaine memory.
AB  - It has been proposed that a memory trace enters a labile phase each time it is
      retrieved. A reactivated memory relies on de novo protein synthesis to be
      faithfully reconsolidated and restored. Thus, in theory, a long-lasting and
      pathological memory associated with drug use may be disrupted by inhibiting its
      reconsolidation through use of protein synthesis inhibitors administered
      immediately following the memory retrieval. However, effective and efficient
      strategies to reactivate drug memory remained elusive. This study was undertaken
      to examine the effects of systemic cycloheximide and anisomycin treatment on the
      reconsolidation and maintenance of a reactivated cocaine-conditioned place
      preference (CPP) in mice using several strategies designed to reactivate the
      previously acquired memory. We found that anisomycin (50 mg/kg/injection) and
      cycloheximide (15 mg/kg/injection) administered immediately after the
      reactivation of cocaine-CPP ameliorated subsequent expression and maintenance of
      this memory. Likewise, when anisomycin and cycloheximide were administered
      immediately after additional cocaine and saline conditioning trials, the
      reactivated memory engendered by those extra training trials was also diminished.
      However, a similar anisomycin dosing regimen failed to affect subsequent
      expression of cocaine-CPP when additional cocaine conditioning trial was used in
      the absence of additional saline trial. Finally, cocaine and saline
      administration to mice in their home cages with or without anisomycin treatment
      had no effect on later cocaine-CPP expression. Taken together, these findings
      suggest that systemic treatment with protein synthesis inhibitors immediately
      after the reactivation of cocaine-CPP effectively diminished the reconsolidation
      and maintenance of such a cocaine memory. More importantly, reactivation of
      cocaine-CPP could be achieved by presentation of cocaine-conditioned cues as well
      as by administering additional cocaine and saline conditioning trials in a
      balanced fashion.

PMID- 20060425
TI  - Neuronal histamine and the interplay of memory, reinforcement and emotions.
AB  - The biogenic amine histamine is an important neurotransmitter-neuromodulator in
      the central nervous system that has been implicated in a variety of biological
      functions including thermo- and immunoregulation, food intake, seizures, arousal,
      anxiety, reward and memory. The review of the pertinent literature indicates that
      the majority of findings are compatible with the appraisal that the inhibition of
      histaminergic neurotransmission impairs learning and memory formation, decreases
      cortical activation and arousal, has a suppressive effect on behavioral measures
      of fear and anxiety, exponentiates the rewarding effects of drugs of abuse and
      intracranial brain stimulation. In contrast, the stimulation of histaminergic
      neurotransmission can ameliorate learning and memory impairments that are
      associated with various experimental deficit models and pathological conditions.
      Clinical investigations with patients suffering from neurodegenerative diseases
      such as Alzheimer's and Parkinson's disease demonstrate pathological alterations
      in the brain's histaminergic system, which, in some cases are correlated with the
      severity of cognitive deficits. The role of the brain's histamine system in
      episodic memory formation and the potential of histamine-related drugs to
      ameliorate cognitive deficits in early stages of neurodegenerative diseases are
      discussed.

PMID- 20060426
TI  - Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying
      conditional learning.
AB  - Rats with combined bilateral lesions of the retrosplenial cortex and the fornix
      or rats with unilateral lesions to the anterior thalamus and the hippocampus,
      made in opposite hemispheres (disconnection preparation), and combined with
      unilateral damage of the retrosplenial cortex in either hemisphere, were tested
      on a spatial-visual conditional learning task in which they learned arbitrary
      associations between stimuli and the scene in which they were embedded. All
      experimental groups were impaired in comparison with normal animals. The more
      severe deficits occurred when (1) both the fornix and the retrosplenial cortex
      were damaged bilaterally thus depriving the hippocampus both from subcortical
      interactions via the fornix and retrosplenial-mediated interactions and (2) when,
      in the crossed lesion preparation, the unilateral retrosplenial lesion was made
      in the hemisphere with the intact hippocampus, again because this lesion would be
      maximally disconnecting the hippocampus from functional interaction with the
      anterior thalamic nucleus and retrosplenial-mediated input.

PMID- 20060427
TI  - A new multiple-drug applicator with minimal drug cross-talk, leakage, and
      consumption.
AB  - The relative effects of multiple drugs give an important clue to dissect a
      neuronal mechanism and to seek for a candidate neurotherapeutical agent. Here we
      have devised a "flute" applicator which can deliver several drugs to a neural
      cell preparation. The applicator stands by, cleaning itself with bath perfusate
      and delivers drugs only during test applications. This minimizes drug cross-talk
      in and leakage from the applicator and drug consumption. Using the applicator, we
      successfully compared the relative effects of widely different doses of an
      agonist in single neurons. The flute applicator would be a useful tool for
      pharmacological analyses.

PMID- 20060428
TI  - Automated piecewise power-law modeling of biological systems.
AB  - Recent trends suggest that future biotechnology will increasingly rely on
      mathematical models of the biological systems under investigation. In particular,
      metabolic engineering will make wider use of metabolic pathway models in
      stoichiometric or fully kinetic format. A significant obstacle to the use of
      pathway models is the identification of suitable process descriptions and their
      parameters. We recently showed that, at least under favorable conditions, Dynamic
      Flux Estimation (DFE) permits the numerical characterization of fluxes from sets
      of metabolic time series data. However, DFE does not prescribe how to convert
      these numerical results into functional representations. In some cases, Michaelis
      Menten rate laws or canonical formats are well suited, in which case the
      estimation of parameter values is easy. However, in other cases, appropriate
      functional forms are not evident, and exhaustive searches among all possible
      candidate models are not feasible. We show here how piecewise power-law functions
      of one or more variables offer an effective default solution for the almost
      unbiased representation of uni- and multivariate time series data. The results of
      an automated algorithm for their determination are piecewise power-law fits,
      whose accuracy is only limited by the available data. The individual power-law
      pieces may lead to discontinuities at break points or boundaries between sub
      domains. In many practical applications, these boundary gaps do not cause
      problems. Potential smoothing techniques, based on differential inclusions and
      Filippov's theory, are discussed in Appendix A.

PMID- 20060429
TI  - Sustained release of water-insoluble simvastatin from biodegradable hydrogel
      augments bone regeneration.
AB  - Drug delivery technology is a practically promising way to enhance the
      therapeutic efficacy of drugs. However, there remain some properties of material
      to be improved for drug delivery, such as the biodegradability and
      biocompatibility. In this study, we demonstrate that a biodegradable hydrogel of
      gelatin can achieve the sustained release of water-insoluble simvastatin.
      Biologically active simvastatin can be released accompanied with the
      biodegradation of hydrogel. The biocompatibility issue of material remaining
      after drug release can be practically resolved. Simvastatin was water-solubilized
      by gelatin grafted with L-lactic acid oligomer and mixed with gelatin, followed
      by chemical crosslinking to obtain gelatin hydrogels incorporating simvastatin
      water-solubilized. The hydrogel augments the simvastatin-induced bone
      regeneration given biocompatible gelatin fragments and has its potential to
      deliver a wide range of water-insoluble drugs.

PMID- 20060430
TI  - Synthesis, formulation and in vitro evaluation of a novel microtubule
      destabilizer, SMART-100.
AB  - A novel microtubule destabilizer, substituted methoxybenzoyl-ary-thiazole (SMART)
      100, was synthesized, which showed good anticancer activity in HepG2 cells. SMART
      100 was able to circumvent multidrug resistance (MDR) and effectively inhibited
      the growth of cell lines that overexpress P-glycoprotein (P-gp). SMART-100
      inhibited P-gp activity, which may be responsible for its ability to overcome
      MDR. Since SMART-100 is poorly soluble in water, it was formulated in
      polyethylene-b-poly(D,L-lactide) (PEG-PLA) micelles. The solubility of SMART-100
      was increased by more than 1.1x10(5) folds. SMART-100 loaded PEG-PLA micelles
      could effectively inhibit HepG2 cell growth and arrest cell cycle progression at
      G2/M phase, followed by appearance of a sub-G1 phase, which is indicative of cell
      apoptosis. Increased Caspase-3 activity was also observed when HepG2 cells were
      treated with SMART-100. The anticancer activity of SMART-100 loaded PEG-PLA
      micelles was also evaluated on luciferase expressing C4-2-Luc cell lines by IVIS
      imaging. Our results suggest that SMART-100 has the potential to treat resistant
      cancers.

PMID- 20060431
TI  - Molecular imaging of HPMA copolymers: visualizing drug delivery in cell, mouse
      and man.
AB  - N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers and their drug conjugates are
      some of the most intensively investigated drug delivery systems for over 30years.
      Some of the HPMA copolymer drug conjugates have entered clinical trials. Various
      molecular imaging technologies have been used to investigate the mechanism of
      drug delivery with HPMA copolymers. Fluorescence imaging has been used for the
      study of the process of intracellular drug delivery, including cell binding,
      subcellular trafficking and intracellular fate, of HPMA copolymers and drug
      conjugates. Magnetic resonance imaging and nuclear medicine, including gamma
      scintigraphy, SPECT and PET, have been used for the non-invasive visualization of
      pharmacokinetics, biodistribution and drug targeting efficiency of HPMA
      copolymers in animal models. gamma-Scintigraphy has been used to study HPMA
      copolymer drug conjugates in human patients. The application of imaging
      technologies in the study of HPMA copolymers and properties of the copolymers
      demonstrated by imaging is summarized in this review.

PMID- 20060432
TI  - Real-time measurement of dentinal fluid flow during amalgam and composite
      restoration.
AB  - OBJECTIVES: This study examined changes in the dentinal fluid flow (DFF) during
      restorative procedures and compared permeability after restoration among
      restorative materials and adhesives. METHODS: A class 1 cavity was prepared and
      restored with either amalgam (Bestaloy), or composite (Z-250) with one of two
      etch-and-rinse adhesives (Scotchbond MultiPurpose: MP and Single Bond 2: SB) or
      one of two self-etch adhesives (Clearfil SE Bond: CE and Easy Bond: EB) on an
      extracted human third molar which was connected to a sub-nanoliter fluid flow
      measuring device (NFMD) under 20 cm water pressure. DFF was measured from the
      intact tooth state through the restoration procedures to 30 min after
      restoration, and re-measured at 3 and 7 days post-restoration. RESULTS: Inward
      flow during cavity preparation was followed by outward flow after preparation. In
      amalgam restoration, the outward flow changed into an inward flow during amalgam
      filling, which was followed by a slight outward flow after finishing. In
      composite restoration, MP and SB showed an inward flow and outward flow for the
      rinsing and drying steps, respectively. Application of a hydrophobic bonding
      resin in the MP and CE systems caused a decrease in the flow rate. Air-drying of
      solvent for the CE and EB systems caused a sudden outward flow, whereas light
      curing of the adhesive and composite caused an abrupt inward flow. CONCLUSIONS:
      Each restorative step clearly changed the direction and the rate of the DFF
      during restoration, which could be well identified with NFMD.

PMID- 20060433
TI  - Characterization of a new periplasmic single-domain rhodanese encoded by a sulfur
      regulated gene in a hyperthermophilic bacterium Aquifex aeolicus.
AB  - Rhodaneses (thiosulfate cyanide sulfurtransferases) are enzymes involved in the
      production of the sulfur in sulfane form, which has been suggested to be the
      relevant biologically active sulfur species. Rhodanese domains occur in the three
      major domains of life. We have characterized a new periplasmic single-domain
      rhodanese from a hyperthermophile bacterium, Aquifex aeolicus, with
      thiosulfate:cyanide transferase activity, Aq-1599. The oligomeric organization of
      the enzyme is stabilized by a disulfide bridge. To date this is the first
      characterization from a hyperthermophilic bacterium of a periplasmic
      sulfurtransferase with a disulfide bridge. The aq-1599 gene belongs to an operon
      that also contains a gene for a prepilin peptidase and that is up-regulated when
      sulfur is used as electron acceptor. Finally, we have observed a sulfur-dependent
      bacterial adherence linked to an absence of flagellin suggesting a possible role
      for sulfur detection by A. aeolicus.

PMID- 20060434
TI  - Chromatin remodeling and histone modifications in pituitary tumors.
AB  - Pituitary tumorigenesis infrequently involves intragenic mutations of oncogenes
      or tumor suppressor genes (Asa and Ezzat, 1998, 2002). Increasing evidence
      suggests that signals implicated in pituitary development may be relevant to
      neoplastic changes. Equally as important, accumulating evidence suggests that in
      contrast to other forms of solid neoplasia, pituitary tumors are frequently
      associated with epigenetic changes. In this review we discuss evolving models of
      epigenetic control and use members of the fibroblast growth factor receptor (FGF)
      receptor family as examples of dysregulated signals in pituitary tumorigenesis
      (Asa and Ezzat, 2009).

PMID- 20060435
TI  - Time-dependent effect of ethanol on GnRH and GnRH receptor mRNA expression in
      hypothalamus and testis of adult and pubertal rats.
AB  - Chronic exposure to ethanol suppresses the male reproductive activity which is
      primarily involved in the release of hypothalamic gonadotropin-releasing hormone
      (GnRH). The testicular GnRH and GnRH receptors (GnRH-R) are found in seminiferous
      tubules, which are predicted to act as a local regulator of spermatogenesis,
      although the function is not well known. In this study, we investigated the
      chronic ethanol effect on GnRH mRNA expression in hypothalamus and testis using
      in situ hybridization and RNase protection assay (RPA). The effect of ethanol on
      expressional changes of GnRH and GnRH-R mRNA was observed in adult and pubertal
      rats according to age and time from 2 weeks (short term) and 4 weeks (long term)
      periods. The results showed that GnRH mRNA expression in adult and pubertal rats
      was dramatically decreased in the testis while no significant change was observed
      in hypothalamus after both short and long term exposure to ethanol. The pubertal
      rats showed decrease in testicular GnRH and GnRH-R mRNA expression, whereas GnRH
      mRNA was increased significantly, while GnRH-R mRNA was further decreased after
      long term exposure in adults. This study suggested that chronic ethanol
      administration is more effective to testicular GnRH and GnRH-R mRNA expression
      than hypothalamus and causes a negative effect on the spermatogenesis process.
      Furthermore, our finding suggests that the deteriorative effects of ethanol on
      gonadal activity are more lethal in puberty than adults.

PMID- 20060436
TI  - Neuroprotective effect on retinal ganglion cells by transpupillary laser
      irradiation of the optic nerve head.
AB  - This study demonstrates that subthreshold transpupillary thermotherapy (TTT)
      laser irradiation on optic nerve head protects retinal ganglion cells (RGCs) in
      an optic nerve crush (ONC) model. TTT was performed in right eyes with an 810-nm
      diode laser aimed at the center of the optic nerve head, using the following
      protocol: power 60mW, duration 60s, spot size 500mum. Fluoro-Gold was injected
      into bilateral superior colliculi 5 days before sacrifice and fluorescent gold
      labeled RGCs were counted under fluorescence microscopy. In the ONC group, a
      progressive loss of RGCs was observed; however, in comparison with the ONC group,
      RGCs density was significantly higher (P=0.001, independent samples t-test) at
      day 7 postoperative and only borderline significances were obtained at days 14
      and 28 postoperative (P=0.044 and P=0.045, respectively, independent samples t
      test) in ONC+TTT group, which implies the potential neuroprotective role of TTT.
      This protective effect seems to be heat shock proteins (HSPs) related, because
      intraperitoneal Quercetin (an inhibitor of HSPs, 4mg/kg/day for 7 days) could
      completely abolish this protective effect at days 7, 14 and 28 postoperative
      (P=0.012, P=0.002, and P=0.000, respectively, independent samples t-test).
      Minimal collateral damage of TTT on optic nerve head tissue, peripapillary RGCs
      and the myelin sheath of the optic nerve were observed under transmission
      electron microscopy. These findings suggested that subthreshold TTT might be a
      safe and practical approach to protect RGCs. The underlying mechanisms may
      involve TTT-induced HSPs in RGCs.

PMID- 20060437
TI  - Are optimal levels of testosterone associated with better cognitive function in
      healthy older women and men?
AB  - BACKGROUND: Sex steroids can positively affect the brain and from this it would
      follow that high levels of sex steroids could be associated with better cognitive
      function in older men and women. METHODS: This Healthy Ageing Study sample
      comprised of 521 older participants (51% women) without dementia at baseline,
      with an age range from 64 to 94 years. Testosterone and sex hormone binding
      globulin were measured using the automated Immulite 2000 and analyzed in
      association with baseline memory, global cognitive function and decline (assessed
      using the Mini-Mental Status Examination or MMSE) and controlling for potential
      confounds such as age, education, vascular disease, smoking, diabetes, thyroid
      function, and body mass index. RESULTS: In healthy older men and women, optimal
      levels of testosterone were associated with better MMSE scores at baseline.
      Follow-up analyses indicated that in men, low testosterone levels (OR=.94, 95%
      CI=.88 to 1.00) were a risk factor for a sharp cognitive decline after 2 years,
      perhaps indicative of dementia. Associations were independent of covariates and
      baseline MMSE. Conversely, women at risk for a sharp drop in cognitive function
      showed some evidence for higher calculated free testosterone levels at baseline.
      CONCLUSIONS: Results replicate earlier cross-sectional findings that high levels
      of sex steroids are not associated with better cognitive function in older
      people. In men, age accelerated endocrinological change could be associated with
      dementia pathology. GENERAL SIGNIFICANCE: These data do not support increasing
      testosterone levels to prevent cognitive decline in men and women over 65 years
      of age.

PMID- 20060438
TI  - Functional and in situ hybridization evidence that preganglionic sympathetic
      vasoconstrictor neurons express ghrelin receptors.
AB  - Agonists of ghrelin receptors can lower or elevate blood pressure, and it has
      been suggested that the increases in blood pressure are caused by actions at
      receptors in the spinal cord. However, this has not been adequately investigated,
      and the locations of neurons in the spinal cord that express ghrelin receptors,
      through which blood pressure increases may be exerted, are not known. We
      investigated the effects within the spinal cord of two non-peptide ghrelin
      receptor agonists, GSK894490 and CP464709, and two peptide receptor agonists,
      ghrelin and des-acyl ghrelin, and we used polymerase chain reaction (PCR) and in
      situ hybridization to examine ghrelin receptor expression. I.v. application of
      the non-peptide ghrelin receptor agonists caused biphasic changes in blood
      pressure, a brief drop followed by a blood pressure increase that lasted several
      minutes. The blood pressure rise, but not the fall, was antagonized by i.v.
      hexamethonium. Application of these agonists or ghrelin peptide directly to the
      spinal cord caused only a blood pressure increase. Des-acyl ghrelin had no
      significant action. The maximum pressor effects of agonists occurred with
      application at spinal cord levels T9 to T12. Neither i.v. nor spinal cord
      application of the agonists had significant effect on heart rate or the
      electrocardiogram. Ghrelin receptor gene expression was detected by PCR and in
      situ hybridization. In situ hybridization localized expression to neurons,
      including autonomic preganglionic neurons of the intermediolateral cell columns
      at all levels from T3 to S2. The numbers of ghrelin receptor expressing neurons
      in the intermediolateral cell columns were similar to the numbers of nitric oxide
      synthase positive neurons, but there was little overlap between these two
      populations. We conclude that activation of excitatory ghrelin receptors on
      sympathetic preganglionic neurons increases blood pressure, and that decreases in
      blood pressure caused by ghrelin agonists are mediated through receptors on blood
      vessels.

PMID- 20060439
TI  - Sildenafil prevents mortality and reduces hippocampal damage after permanent,
      stepwise, 4-vessel occlusion in rats.
AB  - The present study evaluated the effects of sildenafil using the 4-vessel
      occlusion (VO)/internal carotid artery (ICA) model of chronic cerebral
      hypoperfusion (HCC). We previously found that permanent, three-stage occlusion of
      the vertebral arteries (VA) and ICA, four-VO/ICA, with an interstage interval
      (ISI) of 7 days was innocuous and caused no structural or functional outcomes in
      rats. Therefore, before testing sildenafil, we evaluated how a reduction in the
      number of occlusion stages (from three stages to two) and a shortening of the ISI
      might impact the survival rate, capacity for learning and memory, and
      histomorphological integrity of the hippocampus. Survival decreased from 100% to
      70%, 62%, and 0% as the ISI was shortened from 7 to 5, 4, or 3 days,
      respectively. Using the two shortest ISIs, sildenafil (0.75-3.0 mg/kg, p.o.)
      abolished the mortality rate by approximately 95%. Profound neurodegeneration
      occurred in the CA1, CA2, CA3, and CA4 hippocampal subfields after an ISI of 4
      days. Despite this, however, memory performance was unaffected. Subsequently,
      sildenafil treatment reduced 4-VO/ICA-induced hippocampal damage. The present
      results suggest that sildenafil may be potentially beneficial in the treatment of
      chronic cerebral hypoperfusion. Further studies should examine the manner by
      which the chronic 4-VO/ICA model may effectively cause cognitive impairment, thus
      improving its applicability in testing the effects of drugs against structural
      and/or functional outcomes of chronic cerebral hypoperfusion.

PMID- 20060440
TI  - A new coumarin from Sarcandra glabra.
AB  - Sarcandracoumarin (1), the first coumarin having a 1-phenylethyl substituent at
      the C-3 position, was isolated along with eleven known phenolic compounds from
      the water extract of Sarcandra glabra. Its structure was elucidated on the basis
      of spectroscopic data. Compound 1 exhibited moderate or weak cytotoxicity against
      several tumor cell lines.

PMID- 20060441
TI  - Choice behavior in spontaneously hypertensive rats: variable vs. fixed schedules
      of reinforcement.
AB  - Spontaneously hypertensive rats (SHR) and Wistar rats were evaluated in the
      successive-encounters procedure (an operant simulation of natural foraging) with
      the idea of assessing differences between them in their preference for variable
      schedules of reinforcement. In this procedure, after satisfying a schedule of
      reinforcement associated with search time, the subjects could "accept" or
      "reject" another schedule of reinforcement associated with handling time. Two
      schedules of reinforcement were available: a fixed interval (FI), and a variable
      interval (VI) with the same mean value. The results indicated preference for the
      variable schedule in both strains, as suggested by the observation that the VI
      was always accepted while the FI was often rejected. The difference in FI
      acceptability between strains was not statistically significant, a result which
      is relevant for the current debate of SHR as an adequate animal model of
      Attention Deficit Hyperactivity Disorder.

PMID- 20060442
TI  - Spontaneous recovery from interference between cues but not from backward
      blocking.
AB  - In the present study, we examined the differential effect on backward blocking
      (BB) and on interference between cues (IbC) of including a delay right before the
      test phase vs. between training phases 1 and 2 in humans. While models of IbC
      predict a spontaneous recovery (SR) of responding if the delay is placed
      immediately before the test instead of between phases 1 and 2, BB models predict
      that no difference should be observed due to the position of the delay. In our
      experiment, we obtained the SR from IbC but not from BB. These results suggest
      that backward blocking and interference between cues are likely to be the result
      of different processes.

PMID- 20060443
TI  - Effects of inorganic polyphosphate on bone sialoprotein gene expression.
AB  - Inorganic polyphosphate (poly(P)) is a biopolymer existing in almost all cells
      and tissues. The biological functions of poly(P) in micro-organisms have been
      extensively investigated in studies of poly(P) in eukaryotic cells, especially
      osteoblasts, and are increasing. Bone sialoprotein (BSP) is thought to function
      in bone mineralization, and is selectively expressed by differentiated
      osteoblasts. In this study, application of sodium phosphate glass type 25 (SPG25,
      12.5 and 125 microM) increased BSP mRNA levels at 12 h in osteoblast-like ROS
      17/2.8 cells. In transient transfection assay, 12.5 and 125 microM SPG25
      increased luciferase activities of the constructs pLUC3 (-116 to +60), pLUC4 (
      425 to +60), pLUC5 (-801 to +60) and pLUC6 (-938 to +60). Introduction of 2 bp
      mutations to the luciferase constructs showed that the effects of SPG25 were
      mediated by a FGF2 response element (FRE) and a homeodomain protein binding site
      (HOX). Luciferase activities induced by SPG25 were blocked by tyrosine kinase
      inhibitor herbimycine A, MAP kinase kinase inhibitor U0126, PI3-kinase/Akt
      inhibitor LY249002 and inorganic phosphate transport inhibitor foscarnet. Gel
      shift analyses showed that both 12.5 and 125 microM SPG25 increased nuclear
      protein binding to FRE and HOX elements. These studies demonstrate that SPG25
      stimulates BSP transcription by targeting FRE and HOX elements in the proximal
      promoter of the rat BSP gene.

PMID- 20060444
TI  - Myb transcription factors in the oomycete Phytophthora with novel diversified DNA
      binding domains and developmental stage-specific expression.
AB  - Transcription factors containing two or three imperfect tandem repeats of the Myb
      DNA-binding domain (named R2R3 and R1R2R3, respectively) regulate important
      processes in growth and development. This study characterizes the structure,
      evolution, and expression of these proteins in the potato pathogen Phytophthora
      infestans and other oomycetes. P. infestans was found to encode five R2R3 and
      nine R1R2R3 transcription factor-like proteins, plus several with additional
      configurations of Myb domains. Sets of R2R3 and R1R2R3 orthologs are well
      conserved in three Phytophthora species. Analyses of sites that bind DNA in
      canonical Myb transcription factors, such as mammalian c-Myb, revealed unusual
      diversification in the DNA recognition helices of the oomycete proteins. While
      oomycete R2R3 proteins contain c-Myb-like helices, R1R2R3 proteins exhibit either
      c-Myb-like or novel sequences. This suggests divergence in their DNA-binding
      specificities, which was confirmed by electrophoretic mobility shift assays.
      Eight of the P. infestans R2R3 and R1R2R3 genes are up-regulated during
      sporulation and three during zoospore release, which suggests their involvement
      in spore development. This is supported by the observation that an oomycete that
      does not form zoospores, Hyaloperonospora arabidopsidis, contains one-third fewer
      of these genes than Phytophthora.

PMID- 20060445
TI  - Proteomic analysis reveals the dynamic association of proteins with translated
      mRNAs in Trypanosoma cruzi.
AB  - Gene regulation is mainly post-transcriptional in trypanosomatids. The stability
      of mRNA and access to polysomes are thought to be tightly regulated, allowing
      Trypanosoma cruzi to adapt to the different environmental conditions during its
      life cycle. Post-transcriptional regulation requires the association between
      mRNAs and certain proteins to form mRNP complexes. We investigated the dynamic
      association between proteins and mRNAs, using poly(T) beads to isolate and
      characterize proteins and protein complexes bound to poly-A+ mRNAs. The protein
      content of these fractions was analyzed by mass spectrometry (LC-MS/MS). We
      identified 542 protein component of the mRNP complexes associated with mRNAs.
      Twenty-four of the proteins obtained were present in all fractions, whereas some
      other proteins were exclusive to a particular fraction: epimastigote polysomal
      (0.37%) and post-polysomal (2.95%) fractions; stress polysomal (13.8%) and post
      polysomal (40.78%) fractions. Several proteins known to be involved in mRNA
      metabolism were identified, and this was considered important as it made it
      possible to confirm the reliability of our mRNP isolation approach. This
      procedure allowed us to have a first insight into the composition and dynamics of
      mRNPs in T. cruzi.

PMID- 20060446
TI  - A draining lymph node assay (DLNA) for assessing the sensitizing potential of
      proteins.
AB  - There is a need for a simple and predictive model to identify the respiratory
      sensitization potential of (novel) proteins. The present study examined the use
      of a mouse draining lymph node assay (DLNA) approach, employing several routes of
      exposure, as a possible starting point for assessing protein sensitization
      potential. Consistent with the experimental procedure for the standard local
      lymph node assay (LLNA), female BALB/c mice were dosed dermally (topical),
      intranasally (IN) or by oropharyngeal aspiration (OP) on days 1, 2 and 3, and
      proliferation in the relevant draining lymph nodes was measured on day 6. For
      each route, the auricular, superficial cervical and tracheobronchial lymph nodes
      (TBLN) were evaluated following treatment with Subtilisin Carlsberg (SUB; a
      potent sensitizer/allergen), ovalbumin (OVA; a potent food allergen), beta
      lactoglobulin (BLG; a moderate food allergen), and keyhole limpet hemocyanin
      (KLH; a strong immunogen with no reports of respiratory sensitization). Initial
      studies with OVA indicated that dermal administration did not stimulate lymph
      node proliferation. Responses in the tracheobronchial lymph node were most
      dramatic (stimulation indices up to 100) and reproducible for both the IN and OP
      routes. In a comparative experiment, all proteins induced lymph node
      proliferation with a rank order potency of SUB>KLH>OVA>BLG. The influence of the
      endotoxin content on lymph node proliferation was determined to be minimal, and
      did not impact the rank order potency. Molecular characterization of the TBLN at
      an equipotent proliferative dose was conducted for select gene transcripts based
      on research examining chemical sensitizers. Expression profiles differed among
      the four proteins, but the relevance of these responses was not clear and they
      did not further discriminate their allergic potential. These data illustrate both
      the opportunities and challenges associated with the examination of the draining
      lymph node proliferative response to assess the allergenic potential of proteins.

PMID- 20060447
TI  - Ochratoxin A induces G(2) phase arrest in human gastric epithelium GES-1 cells in
      vitro.
AB  - Ochratoxin A (OTA) is a mycotoxin commonly found in several food commodities
      worldwide. OTA exposure was involved in the nephrotoxicity, hepatotoxicity as
      well as immunotoxicity in experimental model. Our previous study showed that the
      high level of OTA contamination in wheat might be related to the high incidence
      of gastric carcinoma in rural area of China. However, there were no available
      data regarding the gastric toxicity of OTA up to now. In the present study, we
      explored the toxicity of OTA in human gastric epithelium immortalized cells (GES
      1) by analyzing the regulation of the cell cycle, apoptosis and its molecular
      mechanism. We found that OTA could induce GES-1 cells arrested in G(2)/M phase.
      Among these cycle-arrested cells, the proportion of cells in M phase was down
      regulated after OTA treatment by the mitotic index and the level of phospho
      histone H3. Thus, it was clear that OTA exerted a major influence on G(2) phase
      arrest instead of M phase. We further detected the expression of the key factors
      which are critical to the G(2)/M phase transmission such as Cdc25C, Cdc2 and
      cyclinB1. The cyclinB1-Cdc2 complex was reduced and the expression of Cdc25C,
      Cdc2 and cyclinB1 were significantly decreased by OTA treatment both at protein
      and mRNA level, respectively. Considering that the cells may undergo apoptosis or
      death due to the cell cycle arrest, so we next detected the apoptosis of cells by
      OTA treatment. The results confirmed that OTA did induce apoptosis of GES-1 cells
      and activate the cleavage of capase-3. In conclusion, cell apoptosis and G(2)
      phase arrest mediated by Cdc25C, Cdc2 and cyclinB1 may be the initiating event in
      the gastric toxicity of OTA.

PMID- 20060448
TI  - Novel multifunctional pharmaceutical excipients derived from microcrystalline
      cellulose-starch microparticulate composites prepared by compatibilized reactive
      polymer blending.
AB  - The choice of excipients remains a critical factor in pharmaceutical
      formulations. Microcrystalline cellulose-maize starch composites (MCC-Mst) have
      been prepared by mixing colloidal dispersions of microcrystalline cellulose (MCC)
      with 10% (w/w) of chemically gelatinized maize starch (Mst) at controlled
      temperature conditions for use as multifunctional excipients with direct
      compression and enhanced disintegration abilities. The novel excipient was
      evaluated for its direct compression and enhanced disintegrant properties and the
      result compared with the properties of the individual components. Some of its
      physicochemical and thermal properties were also determined together with effects
      of freeze-thaw cycles of processing on the functional and physicochemical
      properties. The scanning electron micrograph (SEM) shows that the particles of
      the MCC-Mst were irregular in shape and multiparticulate with a marked degree of
      asperity. The indirect assessment of the powder flow properties as determined by
      Carr's compressibility index and angle of repose showed that the MCC-Mst
      possesses better flow compared with MCC and Mst. MCC-Mst is moderately
      hygroscopic and shows a Type III moisture sorption isotherm. The FT-IR spectra
      and DSC thermograms of the composite were different from those of MCC and Mst.
      The hardness of aspirin tablets was enhanced by incorporating MCC-Mst and MCC,
      but was reduced by Mst. While the tablets prepared with MCC-Mst and Mst
      disintegrated within 7min, aspirin compacts devoid of any excipient and those
      prepared with MCC did not disintegrate even after 2h. Acetaminophen compacts
      prepared with MCC and MCC-Mst showed similar compact hardness characteristics and
      loading properties. The loading capacity of the different samples of the
      composite decreased with increase in the freeze-thaw cycles. The loading capacity
      of the different materials as assessed by their compact hardness efficiency can
      be represented as follows (MCC>T0>T1>T4>T3>T2>Mst). Generally, the different
      samples of MCC-Mst are characterized by physicochemical and functional properties
      that are similar at different degrees to MCC and Mst.

PMID- 20060449
TI  - Silk fibroin nanoparticles for cellular uptake and control release.
AB  - Silk nanoparticles were prepared from silk fibroin solutions of domesticated
      Bombyx mori and tropical tasar silkworm Antheraea mylitta and investigated in
      respect to its particle size, surface charge, stability and morphology along with
      its cellular uptake and release of growth factors. The nanoparticles were stable,
      spherical, negatively charged, 150-170nm in average diameter and exhibited mostly
      Silk II (beta-sheet) structure and did not impose any overt toxicity. Cellular
      uptake studies showed the accumulation of fluorescence isothiocyanate conjugated
      silk nanoparticles in the cytosol of murine squamous cell carcinoma cells. In
      vitro VEGF release from the nanoparticles showed a significantly sustained
      release over 3 weeks, signifying the potential application as a growth factor
      delivery system.

PMID- 20060450
TI  - Effect of aqueous solubility of grafted moiety on the physicochemical properties
      of poly(d,l-lactide) (PLA) based nanoparticles.
AB  - In order to evaluate the solubility effect of grafted moiety on the
      physicochemical properties of poly(d,l-lactide) (PLA) based nanoparticles (NPs),
      two materials of completely different aqueous solubility, polyethylene glycol
      (PEG) and palmitic acid were grafted on PLA backbone at nearly the same grafting
      density, 2.5% (mol of grafted moiety/mol of lactic acid monomer). Blank and
      ibuprofen-loaded NPs were fabricated from both polymers and their properties were
      compared to PLA homopolymer NPs as a control. NPs were analyzed for major
      physicochemical parameters such as encapsulation efficiency, size and size
      distribution, surface charge, thermal properties, surface chemistry, % poly(vinyl
      alcohol) (PVA) adsorbed at the surface of NPs, and drug release pattern.
      Encapsulation efficiency of ibuprofen was found to be nearly the same for both
      polymers approximately 36% and 39% for PEG2.5%-g-PLA and palmitic acid2.5%-g-PLA
      NPs, respectively. Lyophilized NPs of palmitic acid2.5%-g-PLA either blank or
      loaded showed larger hydrodynamic diameter ( approximately 180nm) than PEG2.5%-g
      PLA NPs ( approximately 135nm). PEG2.5%-g-PLA NPs showed lower % of PVA adsorbed
      at their surface ( approximately 5%, w/w) than palmitic acid2.5%-g-PLA NPs (
      approximately 10%, w/w). Surface charge of palmitic acid2.5%-g-PLA NPs seems to
      be influenced by the large amount of PVA remains associated within their matrix.
      Thermal analysis using DSC revealed possible drug crystallization inside NPs.
      Both AFM phase imaging and XPS studies revealed the tendency of PEG chains to
      migrate towards the surface of PEG2.5%-g-PLA NPs. While, XPS analysis of palmitic
      acid2.5%-g-PLA NPs showed the tendency of palmitate chains to position themselves
      into the inner core of the forming particle avoiding facing the aqueous phase
      during NPs preparation using O/W emulsion method. The in vitro release pattern
      showed that PEG2.5%-g-PLA NPs exhibited faster release rates than palmitic
      acid2.5%-g-PLA NPs. PEG and palmitate chains when grafted onto PLA backbone,
      different modes of chain organization during NPs formation were obtained,
      affecting the physicochemical properties of the obtained NPs. The obtained
      results suggest that the properties of PLA-based NPs can be tuned by judicious
      selection of both chemistry and solubility profile of grafted material over PLA
      backbone.

PMID- 20060451
TI  - The role of intermolecular interactions with penetratin and its analogue on the
      enhancement of absorption of nasal therapeutic peptides.
AB  - We investigated the relationship between intermolecular binding and the ability
      of novel cell-penetrating peptides (CPPs) to enhance the nasal absorption of
      therapeutic peptides and proteins. The absorption-enhancing effect of a novel l
      penetratin analogue, 'shuffle (R,K fix) 2' coadministered with different
      biotherapeutic peptides was evaluated after nasal administration in rats. Shuffle
      (R,K fix) 2 significantly increased the nasal absorption of insulin, glucagon
      like-peptide-1 (GLP-1) and exendin-4, compared with the absorption seen with l
      penetratin. Intermolecular binding was analyzed by surface plasmon resonance
      (SPR)-based binding assay. The binding characteristics implied that the higher
      the amount of CPP bound, the greater the nasal drug absorption. In addition, the
      calculated binding ratio between CPP and drug proved a critical aspect in
      enhancing the absorption of insulin and GLP-1. This difference in the enhancing
      effect of CPPs on nasal drug absorption is attributed to the degree of binding
      with the therapeutic macromolecule.

PMID- 20060452
TI  - Transport characteristics of mouse concentrative nucleoside transporter 1.
AB  - Concentrative nucleoside transporter 1 (CNT1, SLC28A1) is a key molecule for
      determining the pharmacokinetic/pharmacodynamic profile of a candidate compound
      derived from a pyrimidine nucleoside, but there is no available information on
      the differences in the functional profile of this ortholog between man and mouse.
      Here, using a clone of mouse CNT1 (mCNT1), we investigated its transport
      characteristics and substrate specificity for synthetic nucleoside analogues, and
      compared them with those of human CNT1 (hCNT1). In mCNT1-transfected Cos-7 cells,
      pyrimidine, but not purine, nucleosides showed sodium- and concentration
      dependent uptake, and uridine uptake was competitively inhibited by uridine
      analogues, the rank order of the inhibitory effects being 5-bromouridine>3'
      deoxyuridine>2'-deoxyuridine. cis- and trans-Inhibition studies involving
      synthetic nucleoside drugs revealed that gemcitabine and zidovudine greatly
      inhibited [(3)H]uridine uptake mediated by mCNT1 in the both cases, while
      cytarabine and zalcitabine showed small cis-inhibitory effect, and no trans
      inhibitory effect on the uptake. These results demonstrate that the transport
      characteristics of mCNT1 are almost the same as those of hCNT1, suggesting that
      mice may be a good animal model in evaluation of pyrimidine nucleoside analogues
      as to their applicability in human therapy.

PMID- 20060453
TI  - In vitro permeation and in vivo whitening effect of topical hesperetin
      microemulsion delivery system.
AB  - Hesperetin is one of the flavonoids and possess anti-inflammatory, UV-protecting
      and antioxidant effects. Permeation issues for topical delivery systems of such
      effects are occasionally problematic, and in view of the fact that microemulsions
      are potential carriers for transdermal delivery system, the objective of this
      study was to design an optimal microemulsion formulation by in vitro permeation
      study for hesperetin topical dosage form and determine its topical
      photoprotective effect and skin irritation by in vivo study. The hesperetin
      loaded microemulsion showed an enhanced in vitro permeation compared to the
      aqueous and isopropyl myristate (IPM) suspension dosage form of hesperetin. In
      comparison, the effect of co-surfactant on the drug permeation capacity,
      propylene glycol showed highest permeation rate, followed by ethanol, glycerol
      and polyethylene glycol (PEG 400). Sunscreen agent padimate O, as a transdermal
      enhancer could increase the permeation rate of hesperetin. In case of in vivo
      study, the hesperetin-loaded microemulsion showed significant topical whitening
      effect and diminished skin irritation when compared with the non-treatment group,
      indicating that the hesperetin microemulsion could be used as an effective
      whitening agent.

PMID- 20060454
TI  - Microencapsulation of self-microemulsifying system: improving solubility and
      permeability of furosemide.
AB  - The primary goal of this study was to formulate Ca-pectinate microcapsules with
      self-microemulsifying core to enhance the solubility and permeability of BCS
      class IV drug furosemide. An Inotech IE-50R encapsulator equipped with a
      concentric nozzle was utilized to transform liquid self-microemulsifying system
      (SMES) to solid microcapsules. Self-microemulsifying core was optimized with
      respect to drug loading capacity and encapsulation efficiency and evaluated for
      its impact on furosemide permeability through rat small intestine and Caco-2 cell
      monolayers. Retention of the core phase was considerably improved (up to 70-80%)
      by optimization of the SMES and microcapsules' drying process. Incorporation of
      furosemide in self-microemulsifying core of microcapsules resulted in improved
      permeability and drug release characteristics in comparison to microspheres
      (without SMES in the core). The obtained results illustrate the prospective use
      of microcapsules with self-microemulsifying core for the delivery of compounds
      with poor biopharmaceutical properties via the oral route.

PMID- 20060455
TI  - Monitoring the aggregation behaviour of self-assembling polymers through high
      resolution ultrasonic spectroscopy.
AB  - Poloxamer 407 is a well-known self-assembling polymer with a wide range of
      temperature- and concentration-dependent phase behaviour, such as micellization
      and gelation. This work was carried out to demonstrate the potential of high
      resolution ultrasonic spectroscopy in evaluating aggregation-deaggregation
      behaviour of self-assembling polymers. In order to achieve this objective, six
      different concentrations of Poloxamer 407 water dispersion were prepared and
      analysed between 5 and 35 degrees C using ultrasonic spectroscopy. For
      comparison, the same samples were also analysed by the DSC technique. The results
      showed that polymer aggregation process can be successfully monitored using both
      ultrasonic parameters of sound speed and attenuation. Furthermore, good agreement
      with DSC data was observed in terms of characteristic transition temperatures and
      also in terms of micellization kinetics and related parameters.

PMID- 20060456
TI  - Pharmacokinetics analysis of sustained release hGH biodegradable implantable
      tablets using a mouse model of human ovarian cancer.
AB  - This paper presents the pharmacokinetic of human growth hormone (hGH) implantable
      tablets tested on a human ovarian cancer mouse model. In order to obtain a
      sustained release device which permits to administer a high dose of the hormone
      that keeps its integrity and stability, three different formulations of hGH-poly
      (d,l-lactic-co-glycolic acid) (PLGA) were elaborated by direct compression method
      varying hormone load, PLGA content and compactation time. In vitro studies showed
      that drug release was mainly controlled by hormone load. Pharmacokinetic studies
      were conducted by using immunodeficient female mice. Four days before the
      insertion of hGH implantable tablets in the peritoneal cavity, every mouse
      received 5x10(6) human ovarian cancer cells (SKOV3.ip1). Hormone serum levels
      were monitored through bleeding from eye orbital vessels. The population
      pharmacokinetic model used was based on the in series tank model and model
      parameters were estimated using the maximum likelihood method. The null
      hypothesis test about differences between formulations leads us to the conclusion
      that the three formulations showed the same kinetic behavior except for the hGH
      load. The hormone release was extended all over 2 weeks but no increase or
      decrease in survival time was observed. These results suggest that hGH serum
      levels do not facilitate tumoral cells proliferation, an expected effect of hGH
      and this could explain why survival times of mice treated with implantable
      tablets are not shorter than those treated with the control ones.

PMID- 20060457
TI  - Enhanced bioavailability of lacidipine via microemulsion based transdermal gels:
      formulation optimization, ex vivo and in vivo characterization.
AB  - The purpose of the present study was to develop and optimize the microemulsion
      based transdermal therapeutic system for lacidipine (LCDP), a poorly water
      soluble and low bioavailable drug. The pseudo-ternary phase diagrams were
      developed for various microemulsion formulations composed of isopropyl myristate,
      Tween 80 and Labrasol. The microemulsion was optimized using a three-factor,
      three-level Box-Behnken design, the independent variables selected were isopropyl
      myristate, surfactant mixture (Tween 80 and Labrasol) and water; dependent
      variables (responses) were cumulative amount permeated across rat abdominal skin
      in 24h (Q(24); Y(1)), flux (Y(2)), and lag time (Y(3)). Mathematical equations
      and response surface plots were used to relate the dependent and independent
      variables. The regression equations were generated for responses Y(1), Y(2) and
      Y(3). The statistical validity of the polynomials was established, and optimized
      formulation factors were selected by feasibility and grid search. Validation of
      the optimization study with 10 confirmatory runs indicated high degree of
      prognostic ability of response surface methodology. The gel of optimized
      formulation (ME-OPT) showed a flux of 43.7microgcm(-2)h(-1), which could meet the
      target flux (12.16microgcm(-2)h(-1)). The bioavailability studies in rabbits
      showed that about 3.5 times statistically significant (p<0.05) improvement in
      bioavailability, after transdermal administration of microemulsion gel compared
      to oral suspension. The ex vivo-in vivo correlation was found to have biphasic
      pattern and followed type A correlation. Microemulsion based transdermal
      therapeutic system of LCDP was developed and optimized using Box-Behnken
      statistical design and could provide an effective treatment in the management of
      hypertension.

PMID- 20060458
TI  - Overcoming cisplatin resistance of ovarian cancer cells by targeted liposomes in
      vitro.
AB  - The clinical application of cisplatin to treat solid tumours is often limited by
      the development of tumour cell resistance against this cytostatic agent. Although
      liposomal carriers of cisplatin are currently in clinical development, approaches
      to functionally overcome cisplatin resistance by liposomes have hardly been
      reported. We prepared PEGylated cisplatin-containing liposomes with diameters of
      about 110 nm and targetability to transferrin receptors (TfR) to correlate
      cisplatin cell uptake with cytotoxicity in sensitive and cisplatin resistant
      ovarian cancer cells A2780 compared to the free drug. Whereas the cell entry of
      free cisplatin was reduced by factor 4 after 24h in resistant cells, liposomal
      uptake was similar in both cell lines and not affected by resistance.
      Cytotoxicity was clearly related to intracellular platinum levels, which were
      even higher for liposomal vs. free cisplatin in the resistant cells after 24, 48,
      and 72 h and slightly lower in the sensitive cells. However, TfR targeting was of
      less impact on activity in comparison to non-targeted liposomes. Detection of
      cellular ATP levels within 24h allowed postulations on the intracellular fate of
      the liposomes. Altogether, this study strongly supports approaches to overcome
      cisplatin resistance by a liposomal application of the drug.

PMID- 20060459
TI  - Morphological effect of lipid carriers on permeation of lidocaine hydrochloride
      through lipid membranes.
AB  - We have studied how the transdermal delivery of lidocaine hydrochloride (LHC) is
      affected by the morphology of lipid carriers, liposomes and micelles, having the
      same lipid composition of 1-stearoyl-sn-glycero-3-phosphocholine (LPC) and
      cholesteryl hemisuccinate (CHEMS). In vitro drug permeation study, carried out on
      guinea pig skin, has revealed that the liposomes made of LPC and CHEMS
      significantly enhance the permeation rate of entrapped LHC; by contrast, the
      mixed micelles with the same composition decrease the degree of delivering co
      existing LHC. Basically, we have also investigated the release kinetics of LHC
      through the cellulose membrane and found that both liposomes and micelles have a
      similar releasing profile. To experimentally demonstrate this unique behavior, we
      have observed the fluidity of stratum corneum liposomal membranes in the presence
      of either our liposomes or micelles. From this study, we have found that
      LPC/CHEMS liposomes fluidize the lipid membrane of stratum corneum lipids;
      however, lipid micelles rather make the membrane rigid. These findings highlight
      that controlling the morphology of drug carriers provides us with a means to
      modulate the permeability of encapsulated drug molecules.

PMID- 20060460
TI  - Gentamicin is ototoxic to all hair cells in the fish lateral line system.
AB  - Hair cells of the lateral line system in fish may differ in their susceptibility
      to damage by aminoglycoside antibiotics. Gentamicin has been reported to damage
      hair cells within canal neuromasts, but not those within superficial neuromasts.
      This finding, based on SEM imaging, indicates a distinction in the physiology of
      hair cells between the two classes of neuromast. Studies concerned with the
      individual roles of canal and superficial neuromasts in behavior have taken
      advantage of this effect in an attempt to selectively disable canal neuromasts
      without affecting superficial neuromast function. Here we present an experimental
      test of the hypothesis that canal neuromasts are more vulnerable to gentamicin
      than superficial neuromasts. We measured the effect of gentamicin exposure on
      hair cells using vital stains (DASPEI and FM1-43) in the neuromasts of Mexican
      blind cave fish (Astyanaxfasciatus) and zebrafish (Daniorerio). Contrary to the
      findings of prior studies that used SEM, gentamicin significantly reduced dye
      uptake by hair cells of both canal and superficial neuromasts in both species.
      Therefore, lateral line hair cells of both neuromast types are vulnerable to
      gentamicin ototoxicity. These findings argue for a re-evaluation of the results
      of studies that have used gentamicin to differentiate the roles of the two
      classes of neuromast in fish behavior.

PMID- 20060461
TI  - Effects of a high-frequency augmented acoustic environment on parvalbumin
      immunolabeling in the anteroventral cochlear nucleus of DBA/2J and C57BL/6J mice.
AB  - Neurons in the anteroventral cochlear nucleus (AVCN) of DBA/2J (D2) and C57BL/6J
      (B6) mice were immunohistochemically labeled for the calcium binding protein
      parvalbumin (PV). Prior to this, mice were treated for 12h nightly with a "high
      frequency" augmented acoustic environment (HAAE: repetitive bursts of a 70 dB
      sound pressure level, half-octave noise band centered at 20 kHz). This was done
      during the period that hearing loss occurs: pre-weaning to 55 days in D2 mice and
      weaning to 9 months in B6 mice. After HAAE treatment in D2 mice, high-frequency
      hearing loss was ameliorated and fewer PV-labeled neurons were found in the AVCN
      compared to untreated controls. HAAE treatment in B6 mice exacerbated high
      frequency hearing loss, yet the number of PV-labeled AVCN neurons in treated mice
      did not differ significantly from that of control mice. The findings suggest that
      HAAE treatment provides relief from physiological stress caused by deprivation of
      auditory input from the impaired cochlea.

PMID- 20060462
TI  - Nano-SiO2 induces apoptosis via activation of p53 and Bax mediated by oxidative
      stress in human hepatic cell line.
AB  - Nanoparticles such as nano-SiO(2) are increasingly used in food, cosmetics,
      diagnosis, imaging and drug delivery. However, toxicological data of nano-SiO(2)
      on hepatic cells in vitro and their detailed molecular mechanisms still remain
      unclear. In order to assess toxicity of nano-SiO(2), L-02 cells were exposed to
      0.2, 0.4 and 0.6 mg/ml of SiO(2) colloids (21, 48 and 86 nm) for 12, 24, 36 and
      48h. Lactate dehydrogenase released from damaged cells were quantified, cellular
      ultrastructural organization was observed, and the levels of reactive oxygen
      species (ROS), lipid peroxidation and glutathione were measured. Apoptosis
      induced by 21 nm SiO(2) was characterized by annexin V-FITC/PI staining and DNA
      ladder assay. Furthermore, apoptosis related proteins such as p53, Bax and Bcl-2
      were analyzed by using western blot analysis. Our data indicated that nano-SiO(2)
      caused cytotoxicity in size, dose and time dependent manners. Oxidative stress
      and apoptosis were induced by exposure to 21 nm SiO(2). Moreover, the expression
      of p53 and Bax was increased in time and dose dependent patterns, whereas the
      expression of Bcl-2 was not significantly changed. In conclusion, ROS-mediated
      oxidative stress, the activation of p53 and up-regulation of Bax/Bcl-2 ratio are
      involved in mechanistic pathways of 21 nm SiO(2) induced apoptosis in L-02 cells.

PMID- 20060463
TI  - Cigarette smoke total particulate matter increases mucous secreting cell numbers
      in vitro: a potential model of goblet cell hyperplasia.
AB  - Cigarette smoking is associated with chronic obstructive pulmonary disease (COPD)
      -a term encompassing chronic lung inflammation, chronic bronchitis and emphysema.
      Goblet cell hyperplasia is a characteristic feature of the lung epithelium in
      COPD patients contributing to the overproduction of airway mucus, including mucin
      MUC5AC. Using an in vitro model of differentiated lung epithelium we have
      investigated morphological and cellular changes in response to interleukin (IL)
      13 (2.5-20 ng/ml), cigarette smoke total particulate matter (TPM; 0.31-20
      microg/ml) and three mainstream cigarette smoke constituents: acrolein,
      formaldehyde and acetaldehyde (all at 0.001-1 microM) over 28 days during
      differentiation (agents replaced daily Monday-Friday). Control cultures of human
      bronchial epithelial cells (HBECs) underwent mucociliary differentiation
      producing a columnar epithelium containing goblet, ciliated and basal cells. Non
      cytotoxic doses of IL-13 induced a significant increase in the percentage of
      MUC5AC positive cells. Using both flow cytometry and immunocytochemical
      techniques for identification of MUC5AC positive cells, TPM treatment induced an
      increase in MUC5AC positive cells, becoming maximal at 5 microg/ml. Acrolein
      treatment also increased the percentage of MUC5AC positive cells. However,
      formaldehyde or acetaldehyde had little effect. This study demonstrates that lung
      toxicants can induce a profound effect on cellular differentiation in an in vitro
      model of the human lung epithelium.

PMID- 20060464
TI  - A principal component regression based genome wide analysis approach reveals the
      presence of a novel QTL on BTA7 for MAP resistance in holstein cattle.
AB  - Bovine Johne's disease (JD), caused by Mycobacterium avium spp. paratuberculosis
      (MAP), causes significant losses to the dairy and beef cattle industries.
      Effective vaccination or therapeutic strategies against this disease are
      currently unavailable and infected animals either get culled or die due to
      clinical disease. An alternative strategy to manage the disease is to selectively
      breed animals with enhanced resistance to MAP infection. Therefore, the objective
      of this study was to identify genetic loci putatively associated with MAP
      infection in a resource population consisting of Holstein cattle using a genome
      wide association approach. The BovineSNP50 BeadChip, containing 54,001 single
      nucleotide polymorphisms (SNPs), was used to genotype 232 animals with known MAP
      infection status. Since, traditional case-control analytical techniques are based
      on single-marker analysis and do not account for the existence of linkage
      disequilibrium (LD) between markers, we used a novel principal component
      regression approach, where each SNP was fit in a logistic regression model, along
      with principal components of other SNPs on the same chromosome showing
      association with the trait, as covariates. Such an approach allowed us to account
      for the LD that exists between multiple markers showing an association on the
      same chromosome. Our analysis revealed the presence of at least 12 genomic
      regions on BTA1, 5, 6, 7, 10, 11 and 14 that were associated with the MAP
      infection status of our resource population. A brief description of these genomic
      regions, and a discussion of the analysis used in this study, have been
      presented.

PMID- 20060465
TI  - Late emerging effects of prenatal and early postnatal nicotine exposure on the
      cholinergic system and anxiety-like behavior.
AB  - Animal models of prenatal nicotine exposure clearly indicate that nicotine is a
      neuroteratogen. Some of the persisting effects of prenatal nicotine exposure
      include low birth weight, behavioral changes and deficits in cognitive function,
      although few studies have looked for neurobehavioral and neurochemical effects
      that might persist throughout the lifespan. Pregnant rats were given continuous
      infusions of nicotine (0.96mg/kg/day or 2.0mg/kg/day, freebase) continuing
      through the third trimester equivalent, a period of rapid brain development.
      Because the third trimester equivalent occurs postnatally in the rat (roughly the
      first week of life) nicotine administration to neonate pups continued via
      maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and
      early postnatal development had an anxiogenic effect on adult rats (P75) in the
      elevated plus maze (EPM), and blocked extinction learning in a fear conditioning
      paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety
      like behavior and cognitive function well into adulthood. In contrast, nicotine
      exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals
      (P30). Analysis of mRNA for the alpha4, alpha7, and beta2 subunits of nicotinic
      acetylcholine receptors revealed lower expression of these subunits in the adult
      hippocampus and medial prefrontal cortex following pre- and postnatal nicotine
      exposure, suggesting that nicotine altered the developmental trajectory of the
      brain. These long-term behavioral and neurochemical changes strengthen the case
      for discouraging cigarette smoking during pregnancy and clearly indicate that the
      use of the patch as a smoking cessation aid during pregnancy is not a safe
      alternative.

PMID- 20060466
TI  - The bile acid sensor FXR regulates insulin transcription and secretion.
AB  - Farnesoid X Receptor plays an important role in maintaining bile acid,
      cholesterol homeostasis and glucose metabolism. Here we investigated whether FXR
      is expressed by pancreatic beta-cells and regulates insulin signaling in
      pancreatic beta-cell line and human islets. We found that FXR activation induces
      positive regulatory effects on glucose-induced insulin transcription and
      secretion by genomic and non-genomic activities. Genomic effects of FXR
      activation relay on the induction of the glucose regulated transcription factor
      KLF11. Indeed, results from silencing experiments of KLF11 demonstrate that this
      transcription factor is essential for FXR activity on glucose-induced insulin
      gene transcription. In addition FXR regulates insulin secretion by non-genomic
      effects. Thus, activation of FXR in betaTC6 cells increases Akt phosphorylation
      and translocation of the glucose transporter GLUT2 at plasma membrane, increasing
      the glucose uptake by these cells. In vivo experiments on Non Obese Diabetic
      (NOD) mice demonstrated that FXR activation delays development of signs of
      diabetes, hyperglycemia and glycosuria, by enhancing insulin secretion and by
      stimulating glucose uptake by the liver. These data established that an FXR-KLF11
      regulated pathway has an essential role in the regulation of insulin
      transcription and secretion induced by glucose.

PMID- 20060467
TI  - Improving sublingual delivery of weak base compounds using pH(max) concept:
      application to propranolol.
AB  - The purpose of the present work was to provide theoretical and experimental
      support in generating an optimal pH (pH(max)) for a representative weak base
      compound (propranolol), that can lead to enhanced sublingual absorption.
      Initially equations for pH-solubility and pH-permeability profiles were derived
      and compared to the profiles obtained experimentally. Excellent correlation
      (R(2)=0.999) of solubility profiles was obtained using non-linear regression, and
      the permeability profiles further predicted that at certain pH (pH(max)), optimal
      mucosal permeation could be achieved. Subsequently, in a pharmacokinetics study,
      a buffered sublingual propranolol tablet, designed to achieve its pH(max) (when
      dissolved in saliva), were compared to that from a marketed product (Inderal)
      which could not achieve pH(max)) in 8 healthy subjects. Each subject received the
      products sublingually for 15 min followed by swallowing the remaining drug
      saliva. The plasma propranolol concentrations of AUC during first 30 min from the
      buffered tablet were significantly higher than that from the Inderal tablet
      (p<0.05), and no significant differences in the remaining AUC were observed.
      These in vitro and in vivo results on propranolol provided experimental
      confirmation of the pH(max) concept as well as its utility in sublingual drug
      delivery. Such an approach may be applicable to other similar compounds to
      improve sublingual drug delivery.

PMID- 20060468
TI  - New approach to hydrophobic cyanine-type photosensitizer delivery using polymeric
      oil-cored nanocarriers: hemolytic activity, in vitro cytotoxicity and
      localization in cancer cells.
AB  - We report on encapsulation of cyanine IR-768 in oil-in-water (o/w) microemulsion,
      i.e. fabrication of templated polymeric nanocapsules as effective nanocarriers
      for a new generation of photodynamic agents suitable for photodynamic therapy
      (PDT). Discussed here are nanocapsule imaging, their in vitro biological
      evaluation, cyanine encapsulation potential, and the cellular localization of
      cyanine IR-768 delivered in the nanocapsules to MCF-7 cancer cells. Oil-cored
      poly(n-butyl cyanoacrylate) (PBCA) nanocapsules were prepared by interfacial
      polymerization in o/w microemulsions formed by the nonionics Tween 80
      (polysorbate 80, polyoxyethylene 20 sorbitan monooleate), and Brij 96
      (polyoxyethylene 10 oleyl ether). Iso-propyl myristate (IPM), ethyl oleate (EOl),
      iso-octane (IO), and oleic acid (OA) were used as the oil phases and iso-propanol
      (IP) and propylene glycol (PG) as the cosurfactants. Such o/w droplets, also
      containing hydrophobic IR-768 in the oil phase, were applied in the interfacial
      polymerization of n-butyl cyanoacrylate at 10 degrees C at pH 5.0. The isolated
      cyanine-loaded nanoparticles were visualized by atomic force microscopy (AFM) and
      scanning electron microscopy (SEM), which proved their unimodal size distribution
      and spherical shape, with diameters dependent upon the monomer content and the
      template type. The entrapment efficiency of cyanine increased with increasing n
      butyl cyanoacrylate concentration and varied from 65.7% to 91.7%. The results of
      in vitro erythrocyte hemolysis and the cell viability of breast cancer MCF-7
      cells showed that the PBCA nanocapsules are quite safe carriers of IR-768 in the
      circulation, having a very low hemolytic potential and being non-toxic to the
      studied cells. Fluorescence microscopy visualized the cyanine intracellular
      distribution and, furthermore, demonstrated that PBCA-nanocarriers effectively
      delivered the IR-768 molecules to the MCF-7 doxorubicin-sensitive and -resistant
      cell lines. Photoirradiation of the cancer cells with entrapped photosensitizer
      decreased cell viability, demonstrating that this effect may be utilized in PDT.

PMID- 20060470
TI  - Molecular characterization and functional analysis of novel
      carboxyl/cholinesterases with GQSAG motif in the silkworm Bombyx mori.
AB  - We have previously cloned and characterized BmJHE, a juvenile hormone (JH)
      selective esterase (JHE) that is important for JH titer regulation in the
      silkworm Bombyx mori. Here, we sought to determine whether multiple genes might
      function as JH-specific esterase in this species. We searched for putative
      carboxyl/cholinesterase (CCE) genes having GQSAG, a highly conserved motif in
      JHE, by the use of silkworm genomic database. Five novel CCE genes (Bmcce-1-5)
      were identified and their cDNA sequences and intron-exon structures were
      determined. We investigated the developmental expression patterns of these CCE
      genes by real-time quantitative PCR analysis and found that their expression
      patterns varied among developmental stages and organs. Of the proteins produced
      by the five genes, only BmCCE-5 had the ability to degrade JH; however, this
      protein might not function as a JH-specific esterase in vivo as it had a high
      K(m) value for JH. On the other hand, BmCCE-5 degraded general esterase
      substrates efficiently. Since Bmcce-5 was strongly expressed in Malpighian
      tubules and the gut, it might function in digestion or xenobiotic metabolism. Our
      results suggest that of the CCEs containing a GQSAG motif only BmJHE can function
      as a JH-specific degradation enzyme in the silkworm.

PMID- 20060469
TI  - Effects of lipophilic emulsifiers on the oral administration of lovastatin from
      nanostructured lipid carriers: physicochemical characterization and
      pharmacokinetics.
AB  - Nanostructured lipid carriers (NLCs) made from mixtures of Precirol and squalene
      were prepared to investigate whether the bioavailability of lovastatin can be
      improved by oral delivery. The size, zeta potential, drug-loading capacity, and
      release properties of the NLCs were compared with those of lipid nanoparticles
      containing pure Precirol (solid lipid nanoparticles, SLNs) and squalene (lipid
      emulsions, LEs). Stable nanoparticles with a mean size range of 180-290 nm and
      zeta potential range of -3 to -35 mV were developed. More than 70% lovastatin was
      entrapped in the NLCs and LEs, which was significantly higher compared to the
      SLNs. The in vitro release kinetics demonstrated that lovastatin release could be
      reduced by up to 60% with lipid nanoparticles containing Myverol as the
      lipophilic emulsifier, which showed a decreasing order of NLCs>LEs>SLNs. Drug
      release was further decreased by soybean phosphatidylcholine (SPC) incorporation,
      with NLCs and SLNs showing the slowest delivery. The oral lovastatin
      bioavailability was enhanced from 4% to 24% and 13% when the drug was
      administered from NLCs containing Myverol and SPC, respectively. The in vivo real
      time bioluminescence imaging indicated superior stability of the Myverol system
      over the SPC system in the gastric environment.

PMID- 20060471
TI  - Late histological and functional changes in the P23H rat retina after
      photoreceptor loss.
AB  - Several strategies have been proposed to restore useful vision following
      photoreceptor degeneration. However, a very few studies have investigated late
      anatomical changes and functional state of residual retinal neurons after
      complete photoreceptor loss. We investigated the progressive degeneration of
      retinal ganglion cells (RGCs) in P23H rats. The RGC multielectrode array
      recordings indicated lower firing rates, disappearance of broad-scale, and
      maintenance of short-scale pairwise correlations. Up to 11% of RGCs displayed
      repetitive and often correlated spike discharges, reminiscent of developmental
      rhythmic activity, which could be reversibly suppressed by blockade of the
      AMPA/kainite glutamate receptors. RGCs in P23H rats remain sensitive to local
      electrical stimulation, generating short-latency responses as in the normal
      retina. These results provide evidence that, despite the demonstrated RGC
      degeneration, remaining active RGCs maintain their basic physiological and
      network properties with some emerging functional changes such as the spontaneous
      rhythmic activity in late stages of the degenerative disease.

PMID- 20060472
TI  - Production and characterization of active hepatitis C virus RNA-dependent RNA
      polymerase.
AB  - The non-structural protein 5B (NS5B) is an essential component for the genome
      replication of hepatitis C virus (HCV). Thus, its activity holds the potential of
      being a target for therapeutic actions against HCV. The availability of large
      amount of functionally active NS5B enzyme may facilitate the identification of
      NS5B inhibitors via high-throughput screening (HTS). Here, we expressed the C
      terminal 20-amino acids truncated NS5B in a bacterial system using the N-terminal
      domain of Escherichia coli lysyl-tRNA synthetase (LysN) as a solubility enhancer.
      The fusion protein (LysN-NS5B) was purified in a yield of 6.2mg/L. The activity
      of LysN-NS5B was confirmed by in vitro RNA-dependent RNA polymerase (RdRp)
      activity assay, and the biochemical properties of LysN-NS5B were further
      characterized by kinetic analysis. The optimal RdRp activity was shown at 30
      degrees C with 5mM of Mg(2+) or 10mM of Mn(2+), while the K(m) value for UTP was
      determined as 5microM. The RdRp activity of LysN-NS5B was strongly inhibited by
      phenyldiketoacid, a specific inhibitor of HCV NS5B activity. Our results suggest
      that the LysN fusion system is a suitable approach for producing an active form
      of NS5B that can be used for HTS of NS5B inhibitors.

PMID- 20060473
TI  - Purification and functional characterization of a Camelid-like single-domain
      antimycotic antibody by engineering in affinity tag.
AB  - Single-domain single-chain variable fragment (scFv) antibody is sometimes
      critical for purification using affinity tagging strategy. We failed in our
      initial effort to purify a prematurely developed Camelid-like E-tagged short scFv
      K2 antibody that contained a complete variable region of the heavy chain and
      partial region of the light chain by using an anti-E-tag affinity column. To
      expedite the purification of this altered but interesting antimycotic agent, we
      replaced a long and large E-tag by a short and hydrophilic 6x-Histidine (His(6))
      affinity tag by polymerase chain reaction. The short and compact His(6)-tag was
      placed on the previously constructed expression vector pCANTAB 5 E that contained
      the large affinity E-tag sequence (13 amino acids) by PCR-based mutagenesis and
      was expressed in Escherichia coli. The recombinant protein can then be purified
      by immobilized metal affinity chromatography (IMAC) and be used for biochemical
      and other functional characterization. This His(6)-tagged short scFv-K2 antibody
      (20 kDa) had strong cytocidal activity against Saccharomyces and Candida species
      with a IC(50) value of 0.44x10(-6)M and 1.10 x 10(-6)M, respectively. Tag
      replacement facilitates the purification of a Camelid-like single-domain scFv
      antibody and after that meets its different functional characteristics. The
      present study reflects that the V(H) domain of the scFv antibody is mainly
      responsible for its biological activity and single-domain scFv antibody may acts
      as a potent antimicrobial agent.

PMID- 20060474
TI  - Purification of untagged HIV-1 reverse transcriptase by affinity chromatography.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) plays an
      essential role in the life cycle of the virus. Therefore, RT has been a primary
      target in the development of antiviral agents against HIV-1. Given the prevalence
      of resistant viruses, evaluation of the resistance profile of potential drug
      candidates is a key step in drug development. A simplified RT purification
      protocol would facilitate this process, as it provides an efficient method by
      which to purify RT variants for compound evaluation. Traditional purification
      protocols require the use of several columns to purify untagged RT. The entire
      procedure usually requires at least one week to complete. Herein, we report two
      novel methods that enable us to purify highly active RT in either one or two
      steps. First, a one-step purification protocol was developed by employing an
      affinity column that was prepared by conjugating an RNase H specific inhibitor
      (RNHI) with NHS-activated resin. Cell lysate containing RT was loaded onto the
      column followed by washing in the presence of 2mM Mn(2+). The RT retained in the
      column was eluted after soaking overnight in 10mM EDTA to retrieve the Mn(2+). In
      the other method, a vector was constructed that encodes RT fused to cleavable
      intein and AviTag (a biotin tag) sequences at the C-terminus. Cell lysate
      containing biotinylated RT was passed through a DE-52 column and then loaded onto
      an avidin column. Untagged RT was released from the column by reductive cleavage
      of the intein by DTT. These two methods significantly shorten the time required
      to purify untagged WT and mutant RTs.

PMID- 20060475
TI  - Antibody-mediated purification of co-expressed antigen-antibody complexes.
AB  - Immunoaffinity is an established chromatographic method for isolating
      macromolecules independently on the presence of specific tags while the tight
      interaction between antigen and antibody has been exploited to stabilize proteins
      during crystallization trials. Therefore, it seems reasonable to try to combine
      the two protocols, namely to co-express the target proteins together with their
      specific antibodies to obtain stable complexes suitable for direct purification
      and further analyses. Using the variable region of single domain llama
      antibodies, we showed that the co-expression of antigen-antibody pairs is
      feasible in both the periplasm and the cytoplasm of bacteria. Moreover, the
      complexes that were formed in vivo could be purified using a tag fused to the
      recombinant antibody and remained stable during gel-filtration. The co-expression
      and co-purification strategy significantly increased the final protein yields
      promoting the accumulation of functional intrabodies. The described method may
      offer a suitable alternative for the purification of proteins intended for
      crystallization trials and it may also be used as a general purification protocol
      for both antigens and recombinant antibodies.

PMID- 20060476
TI  - Expression of immune-related genes in one phase of embryonic development of
      freshwater crayfish, Pacifastacus leniusculus.
AB  - Crayfish do not have larval stage as other crustacean such as penaeid shrimp they
      spawn their eggs until hatching and what hatches out from the eggs are miniature
      crayfish known as juveniles. In order to address the question whether immune
      genes are initially expressed during the embryo development in the egg stage, the
      expression of some immune-related genes: prophenoloxidase (proPO), peroxinectin,
      hemocyanin, anti-lipopolysaccharide factor (ALF), plcrustin, astakine-1, 2 and
      transglutaminase (TGase) were determined in the middle phase of crayfish embryo
      development. Furthermore, immune challenge was used to determine the immune
      response of eggs by immersing them in a solution of the highly pathogenic
      bacterium Aeromonas hydrophila. Semi-quantitative RT-PCR analysis showed that all
      tested genes are present except proPO in this phase of crayfish embryo
      development and none of the genes tested changed their expression following
      immersion in A. hydrophila. The proPO transcript has been reported from hemocytes
      in crustaceans and it plays crucial roles in crustacean immune response. This may
      indicate that the development of immune-competent hemocytes in this stage of
      crayfish embryo is not completed and the egg shell as such plays an important
      role as a shield in protecting the embryo from bacteria and maybe also other
      pathogens.

PMID- 20060477
TI  - Disk abalone (Haliotis discus discus) expresses a novel antistasin-like serine
      protease inhibitor: Molecular cloning and immune response against bacterial
      infection.
AB  - A novel antistasin-like cDNA homologue named as Ab-Antistasin was isolated from
      the disk abalone Haliotis discus discus normalized cDNA library. The Ab
      Antistasin (1398-bp) consisted of an 1185-bp open reading frame encoding 395
      amino acid (aa) residues. The predicted molecular mass and isoelectric point of
      Ab-Antistasin was 44 kDa and 8.5, respectively, and showed highest identity
      (23.1%) to Hydra magnipapillata antistasin. The most striking feature of Ab
      Antistasin is the 12-fold internal repeats (IR) of an antistasin-like domain. Ten
      of the 12 IR domains (26-27 aa) are highly conserved, with 6 cysteines and 1
      glycine. Ab-Antistasin was comprised of three Bowman-Birk serine protease
      inhibitor family motifs. The recombinant Ab-Antistasin (rAb-Antistasin) was over
      expressed in Escherichia coli and purified using a pMAL system. rAb-Antistasin
      (10 microM) was able to inhibit trypsin activity by 66% in a dose-dependent
      manner. Moreover, it exhibited low prolongation activity for coagulation in an
      APTT assay (86.0 s compared to control 42.0 s) with human blood. Endogenous Ab
      Antistasin mRNA was found to be expressed in digestive tract, hepatopancreas,
      hemocytes, abductor muscle and mantle, with highest expression levels in
      digestive tract followed by hepatopancreas and hemocytes. Quantitative real time
      PCR results revealed that Ab-Antistasin transcription was significantly induced
      at 3 h post-infection (p.i.) after challenged by a mixture of bacteria (Vibrio
      alginolyticus, Vibrio parahemolyticus, and Listeria monocytogenes) in the abalone
      digestive tract; in the hemocytes, induction occurred at 6 and 12 h. The results
      indicated that Ab-Antistasin could play an important role in the immune responses
      of mollusks.

PMID- 20060478
TI  - The functional role of motor activation in language processing: motor cortical
      oscillations support lexical-semantic retrieval.
AB  - There is increasing experimental evidence that processing action-related language
      results in the automatic activation of associated regions of the motor and
      premotor cortex. However, the functional significance of motor activation in
      language processing is still under debate. In the present EEG study, we set out
      to investigate if language-induced motor activation primarily reflects the
      retrieval of lexical-semantic information or post-lexical motor imagery. The
      processing of action verbs was found accompanied by an early activation of motor
      related brain areas, as reflected by a desynchronization in the mu- and beta
      frequency bands which was localized to motor and premotor areas. A stronger motor
      activation was observed for verbs presented in an animal context (e.g. "The deer
      jumped over the stream") compared to a human context (e.g. "The athlete jumped
      over the fence") and motor resonance was directly modulated by the cloze
      probability of the noun-verb pairs. The onset of the motor effects preceded
      classical measures of semantic integration (i.e. the N400 component) and the
      strength of motor activation was found inversely related to the size of the N400
      effect. These findings support the hypothesis that motor activation in language
      processing primarily supports the retrieval and integration of lexical-semantic
      information.

PMID- 20060479
TI  - Graph-theory based parcellation of functional subunits in the brain from resting
      state fMRI data.
AB  - Resting-state fMRI provides a method to examine the functional network of the
      brain under spontaneous fluctuations. A number of studies have proposed using
      resting-state BOLD data to parcellate the brain into functional subunits. In this
      work, we present two state-of-the-art graph-based partitioning approaches, and
      investigate their application to the problem of brain network segmentation using
      resting-state fMRI. The two approaches, the normalized cut (Ncut) and the
      modularity detection algorithm, are also compared to the Gaussian mixture model
      (GMM) approach. We show that the Ncut approach performs consistently better than
      the modularity detection approach, and it also outperforms the GMM approach for
      in vivo fMRI data. Resting-state fMRI data were acquired from 43 healthy
      subjects, and the Ncut algorithm was used to parcellate several different
      cortical regions of interest. The group-wise delineation of the functional
      subunits based on resting-state fMRI was highly consistent with the parcellation
      results from two task-based fMRI studies (one with 18 subjects and the other with
      20 subjects). The findings suggest that whole-brain parcellation of the cortex
      using resting-state fMRI is feasible, and that the Ncut algorithm provides the
      appropriate technique for this task.

PMID- 20060480
TI  - Neural correlates of episodic retrieval: an fMRI study of the part-list cueing
      effect.
AB  - Episodic retrieval is supported by multiple forms of cognitive control that
      depend on prefrontal cortex. However, within prefrontal cortex, the regional
      specificity for different control processes is still largely underspecified. Here
      we used fMRI to investigate the processes involved in part-list cueing, a
      phenomenon entailing the reduction of memory performance when some of the "to-be
      remembered items" are presented during retrieval. Retrieval inhibition and
      strategy disruption have been proposed as possible underlying causes of this
      surprising effect. Critically, different encoding conditions can dissociate these
      two hypotheses, as this is thought to have a different impact on strategy-related
      versus inhibition-related processes. Accordingly, we compared part-list versus no
      part-list retrieval conditions, following high versus low associative encoding
      conditions. This revealed activation of the left frontopolar and right
      dorsolateral prefrontal cortex in conditions of part-list cueing retrieval, but
      only following low associative encoding. These results are consistent with the
      inhibitory or interference resolution accounts of part-list cueing, suggesting a
      critical role of between-items competition and high monitoring demands at
      retrieval. In addition, we also examined brain activation during the encoding
      phase, specifying further possible anatomo-functional links between encoding and
      retrieval processes. The results suggest that different encoding conditions
      induce distinct patterns of activation at retrieval, corroborating the idea that
      they promote the adoption of different retrieval strategies. The implications of
      the results are discussed in relation to the cognitive mechanisms of inhibition,
      interference resolution, and encoding/retrieval strategies for episodic memory.

PMID- 20060481
TI  - Rapid semi-automatic segmentation of the spinal cord from magnetic resonance
      images: application in multiple sclerosis.
AB  - A new semi-automatic method for segmenting the spinal cord from MR images is
      presented. The method is based on an active surface (AS) model of the cord
      surface, with intrinsic smoothness constraints. The model is initialized by the
      user marking the approximate cord center-line on a few representative slices, and
      the compact surface parametrization results in a rapid segmentation, taking on
      the order of 1 min. Using 3-D acquired T(1)-weighted images of the cervical spine
      from human controls and patients with multiple sclerosis, the intra- and inter
      observer reproducibilities were evaluated, and compared favorably with an
      existing cord segmentation method. While the AS method overestimated the cord
      area by approximately 14% compared to manual outlining, correlations between cord
      cross-sectional area and clinical disability scores confirmed the relevance of
      the new method in measuring cord atrophy in multiple sclerosis. Segmentation of
      the cord from 2-D multi-slice T(2)-weighted images is also demonstrated over the
      cervical and thoracic region. Since the cord center-line is an intrinsic
      parameter extracted as part of the segmentation process, the image can be
      resampled such that the center-line forms one coordinate axis of a new image,
      allowing simple visualization of the cord structure and pathology; this could
      find wider application in standard radiological practice.

PMID- 20060482
TI  - In vitro and in vivo magnetic resonance imaging (MRI) detection of GFP through
      magnetization transfer contrast (MTC).
AB  - Green fluorescent protein (GFP) is a widely utilized molecular marker of gene
      expression. However, its use in in vivo imaging has been restricted to
      transparent tissue mainly due to the tissue penetrance limitation of optical
      imaging. Here, we report a novel approach to detect GFP with Magnetization
      transfer contrast (MTC) magnetic resonance imaging (MRI). MTC is an MRI
      methodology currently utilized to detect macromolecule changes such as decrease
      in myelin and increase in collagen content. We employed MTC MRI imaging to detect
      GFP both in vitro and in in vivo mouse models. We demonstrated that our approach
      produces values that are protein specific, and concentration dependent. This
      approach provides a flexible, non-invasive in vivo molecular MRI imaging strategy
      that is dependent upon the presence and concentration of the GFP reporter.

PMID- 20060483
TI  - A new Kalman filter approach for the estimation of high-dimensional time-variant
      multivariate AR models and its application in analysis of laser-evoked brain
      potentials.
AB  - In this methodological study we present a new version of a Kalman filter
      technique to estimate high-dimensional time-variant (tv) multivariate
      autoregressive (tvMVAR) models. It is based on an extension of the state-space
      model for a multivariate time series to a matrix-state-space model for multi
      trial multivariate time series. The result is a general linear Kalman filter
      (GLKF). The GLKF enables a tvMVAR model estimation which was applied for
      interaction analysis of simulated data and high-dimensional multi-trial laser
      evoked brain potentials (LEP). The tv partial Granger causality index (tvpGCI)
      was used to investigate the interaction patterns between LEPs derived from an
      experiment with noxious laser stimulation. First, the new approach was compared
      with the multi-trial version of the recursive least squares (RLS) algorithm with
      forgetting factor (Moller et al., 2001) by using 24 distinct electrodes. The RLS
      failed for a channel number (dimension) higher than 24. Secondly, the analysis
      was repeated by using all 58 electrodes and the similarities and differences of
      the GCI-based interaction patterns are discussed. It can be demonstrated that the
      application of high-dimensional tvMVAR modelling will contribute to a better
      understanding of the relationship between structure and function.

PMID- 20060484
TI  - Hepatitis B virus reactivation and efficacy of prophylaxis with lamivudine in
      patients undergoing allogeneic stem cell transplantation.
AB  - Patients previously infected with hepatitis B virus (HBV) undergoing an allograft
      and recipients from HBV carrier donors are at risk of posttransplant viral
      reactivation. The role of prophylaxis with lamivudine remains unclear. One
      hundred seventeen patients, with a median age of 52 years (20-67 years), with
      various hematologic malignancies transplanted between 1999 and 2007 entered the
      study. Eighty-seven recipients negative for HBV surface antigen (HBsAg),
      antihepatitis B core antigen antibodies (anti-HBc), and HBV-DNA with HBsAg and
      HBV-DNA negative donors were defined as at low risk of HBV reactivation, whereas
      all the remaining 30 patients were defined as at high risk. Patients at high risk
      transplanted in 2005 or after received lamivudine to prevent HBV reactivation as
      per the Italian guidelines by the Associazione Italiana per lo Studio del Fegato
      (AISF). Patients at low risk did not experience HBV reactivation/hepatitis. Among
      the recipients at high risk, 11 of 25 anti-HBc positive, those HBsAg positive (2
      of 2) or negative but transplanted from HBsAg positive donors (3 of 3) were
      treated with lamivudine. None of these developed HBV reactivation/hepatitis after
      a median follow-up of 40 months (17-55 months). Hepatitis developed in 3 anti-HBc
      positive untreated patients conditioned with a reduced-intensity regimen.
      Hepatitis B was not observed in recipients at low risk, transplanted from HBsAg
      negative/anti-HBc positive or negative donors. Lamivudine was effective in
      controlling reactivation in: HBsAg positive recipients, in patients transplanted
      from HBsAg positive donors and in HBsAg negative/antiHBc positive recipients, who
      showed a significant risk of reactivation if not given prophylaxis (NCT
      00876148).

PMID- 20060485
TI  - Host-specific differentiation among populations of Venturia inaequalis causing
      scab on apple, pyracantha and loquat.
AB  - Patterns of multilocus DNA sequence variation within and between closely related
      taxa can provide insights into the history of divergence. Here, we report on DNA
      polymorphism and divergence at six nuclear loci in globally distributed samples
      of the ascomycete Venturia inaequalis, responsible for scab on apple, loquat, and
      pyracantha. Isolates from different hosts were differentiated but did not form
      diagnosable distinct phylogenetic species. Parameters of an Isolation-with
      Migration model estimated from the data suggested that the large amount of
      variation shared among groups more likely resulted from recent splitting than
      from extensive genetic exchanges. Inferred levels of gene flow among groups were
      low and more concentrated toward recent times, and we identified two potentially
      recent one-off shifters from apple and pyracantha to loquat. These findings
      support a scenario of recent divergence in allopatry followed by introgression
      through secondary contact, with groups from loquat and pyracantha being the most
      recently differentiated.

PMID- 20060487
TI  - 15-HETE protects rat pulmonary arterial smooth muscle cells from apoptosis via
      the PI3K/Akt pathway.
AB  - 15-Hydroxyeicosatetraenoic acid (15-HETE), a metabolic product of arachidonic
      acid (AA), plays an important role in pulmonary vascular smooth muscle
      remodeling. Although its effects on the apoptotic responses are known, the
      underlying mechanisms are still poorly understood. Since Akt is a critical
      regulator of cell survival and vascular remodeling, there may be a crosstalk
      between 15-HETE anti-apoptotic process and PI3K/Akt survival effect in rat
      pulmonary arterial smooth muscle cells (PASMCs). To test this hypothesis, we
      studied the effect of 15-HETE on cell survival and apoptosis using Western blot,
      cell viability measurement, nuclear morphology determination, TUNEL assay and
      mitochondrial potential analysis. We found that activation of the PI3K/Akt
      signaling system was necessary for the 15-HETE to suppress PASMC apoptosis and
      improve cell survival. Our results indicated that 15-HETE inhibited the apoptotic
      responses of PASMCs, including morphological alterations, mitochondrial
      depolarization and the expression apoptosis-specific proteins. These effects were
      likely to be mediated through the activation of PI3K/Akt. Two downstream signal
      molecules of PI3K/Akt were identified. Both FasL and Bad were down-regulated by
      15-HETE and 15-HETE phosphorylated Bad. These changes depended on the PI3K/Akt
      signaling pathway in PASMCs. Thus a signal transduction pathway was demonstrated
      which is necessary for the effects of 15-HETE in protection PASMCs from
      apoptosis.

PMID- 20060486
TI  - Sex- and tissue-specific effects of waterborne estrogen on estrogen receptor
      subtypes and E2-mediated gene expression in the reproductive axis of goldfish.
AB  - This research examined the gene expression profile of three goldfish estrogen
      receptor (ER) subtypes in multiple tissues in relation to mRNA levels of
      aromatase B and vitellogenin (VTG) following waterborne estrogen exposures. The
      protocol consisted of: i) adult male goldfish in late gonadal recrudescence
      exposed to 1 nM 17beta-estradiol (E2); ii) adult male and female goldfish in
      early sexual regression exposed to 1 nM E2 for 3, 6, 12 and 24h; and, iii)
      sexually mature, adult male goldfish exposed to 0.3 nM 17alpha-ethynylestradiol
      (EE2) for 24h. Liver produced the most consistent response with up-regulation of
      ERalpha in sexually regressed, mature and recrudescing males and in sexually
      regressed females. The dose and length of exposure, reproductive state and sex
      affected the auto-regulation of ERbeta1 by E2. ERbeta2 was not affected in any
      experiments suggesting it may not be auto-regulated by E2. Aromatase B and VTG
      gene expression were affected by E2, but also by other experimental conditions.
      EE2 induced liver ERalpha and VTG mRNA levels indicating that high environmental
      EE2 levels induce E2-mediated gene expression in a model teleost. These studies
      reveal a more complicated action of estrogenic compounds that has important
      implications on estrogenic endocrine disruptors in teleosts.

PMID- 20060488
TI  - Prostaglandin E1 (PGE1), but not prostaglandin E2 (PGE2), alters luteal and
      endometrial luteinizing hormone (LH) occupied and unoccupied LH receptors and
      mRNA for LH receptors in ovine luteal tissue to prevent luteolysis.
AB  - Loss of luteal progesterone secretion at the end of the ovine estrous cycle is
      via uterine PGF(2)alpha secretion. However, uterine PGF(2)alpha secretion is not
      decreased during early pregnancy in ewes. Instead, the embryo imparts a
      resistance to PGF(2)alpha. Prostaglandins E (PGE; PGE(1)+PGE(2)) are increased in
      endometrium and uterine venous blood during early pregnancy in ewes to prevent
      luteolysis. Chronic intrauterine infusion of PGE(1) or PGE(2) prevents
      spontaneous or IUD, estradiol-17beta, or PGF(2)alpha-induced premature luteolysis
      in nonbred ewes. The objective was to determine whether chronic intrauterine
      infusion of PGE(1) or PGE(2) affected mRNA for LH receptors, occupied and
      unoccupied receptors for LH in luteal and caruncular endometrium, and luteal
      function. Ewes received Vehicle, PGE(1), or PGE(2) every 4h from days 10 to 16 of
      the estrous cycle via a cathether installed in the uterine lumen ipsilateral to
      the luteal-containing ovary. Jugular venous blood was collected daily for
      analysis of progesterone and uterine venous blood was collected on day-16 for
      analysis of PGF(2)alpha and PGE. Corpora lutea and caruncular endometrium were
      collected from day-10 preluteolytic control ewes and day-16 ewes treated with
      Vehicle, PGE(1) or PGE(2) for analysis of the mRNA for LH receptors and occupied
      and unoccupied receptors for LH. Luteal weights on day-16 in ewes treated with
      PGE(1) or PGE(2) and day-10 control ewes were similar (P>or=0.05), but were
      greater (P<or=0.05) than in day-16 Vehicle-treated ewes. Progesterone profiles on
      days 10-16 differed (P<or=0.05) among treatment groups: PGE(1)>PGE(2)>Vehicle
      treated ewes. Concentrations of PGF(2)alpha and PGE in uterine venous plasma on
      day-16 were similar (P>or=0.05) in the three treatment groups. Luteal mRNA for LH
      receptors and unoccupied and occupied LH receptors were similar (P>or=0.05) in
      day-10 control ewes and day-16 ewes treated with PGE(2) and were lower
      (P<or=0.05) in day-16 Vehicle-treated ewes. PGE(2) prevented loss (P<or=0.05) of
      day-16 luteal mRNA for LH receptors and occupied and unoccupied LH receptors.
      Luteal and caruncular tissue mRNA for LH receptors and occupied and unoccupied LH
      receptors were greater (P<or=0.05) on day-16 of PGE(1)-treated ewes than any
      treatment group. mRNA for LH receptors and occupied and unoccupied receptors for
      LH in caruncules were greater (P<or=0.05) in day-16 Vehicle or PGE(2)-treated
      ewes than in day-10 control ewes. It is concluded that PGE(1) and PGE(2) share
      some common mechanisms to prevent luteolysis; however, only PGE(1) increased
      luteal and endometrial mRNA for LH receptors and occupied and unoccupied LH
      receptors. PGE(2) prevents a decrease in luteal mRNA for LH receptors and
      occupied and unoccupied receptors for LH without altering endometrial mRNA for LH
      receptors or occupied and unoccupied receptors for LH.

PMID- 20060489
TI  - Acute toxicity and genotoxicity studies on poly(epsilon-caprolactone)
      poly(ethylene glycol)-poly(epsilon-caprolactone) nanomaterials.
AB  - In the present study, we prepared poly(epsilon-caprolactone)-poly(ethylene
      glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanomaterials by solvent
      extraction method. The obtained PCEC nanomaterials were studied extensively for
      acute toxicity and genotoxicity using bacterial reverse mutation test (Ames
      test), chromosomal aberration test and mouse micronucleus test. All of the
      Sprague-Dawley rats did not show any mortality and clinical signs of toxicity
      after intravenous injection at the level of 2.4g/kg body weight. Thus, the LD(50)
      of PCEC nanomaterials was determined to be greater than 2.4g/kg. In Ames test,
      PCEC nanomaterials were negative in Salmonellatyphimurium strains TA97, TA98,
      TA100, TA102, and TA1535 with or without metabolic activation. PCEC nanomaterials
      did not induce chromosomal aberrations in cultured Chinese hamster lung cells up
      to 5000mug/mL with or without metabolic activation. Micronucleus assay
      demonstrated that PCEC nanomaterials did not significantly increase
      micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of ICR mice
      or suppress bone marrow, indicating they did not cause chromosome aberrations. In
      conclusion, our results indicated that PCEC nanomaterials did not cause any acute
      toxicity and genotoxicity in our experimental conditions. Its potential to be a
      candidate of drug carrier is worth being further investigated.

PMID- 20060492
TI  - Cytological defects during embryogenesis in heat-induced tetraploid Kuruma shrimp
      Penaeus japonicus.
AB  - Tetraploid shrimp embryos have been induced; however, in all cases no postlarvae
      were produced. This study determined when tetraploid Penaeus japonicus became non
      viable and identified unique abnormalities to aid in elucidating the causes of
      lethality. Embryonic development was analyzed using flow cytometry to determine
      ploidy and laser scanning confocal microscopy for cytological examination of
      embryogenesis. Abnormalities exclusive to tetraploids were identified from the 1
      cell stage: an off-centre pronucleus, polypolar spindles, delayed time to first
      mitosis and polypolar cleavage. Following first mitosis in the tetraploids, 50%
      of the cells did not contain DNA. This unique abnormality was not resolved later
      in development and is therefore believed to be a lethal trait. Causes of this
      phenomenon likely stemmed from abnormal mitotic spindle regeneration following
      the mitotic heat shock. Consequently, the findings of this study indicate that
      current methods of tetraploidy induction using heat shock appear unsuitable for
      viable tetraploid shrimp production.

PMID- 20060490
TI  - Role of oxidatively induced DNA lesions in human pathogenesis.
AB  - Genome stability is essential for maintaining cellular and organismal
      homeostasis, but it is subject to many threats. One ubiquitous threat is from a
      class of compounds known as reactive oxygen species (ROS), which can
      indiscriminately react with many cellular biomolecules including proteins,
      lipids, and DNA to produce a variety of oxidative lesions. These DNA oxidation
      products are a direct risk to genome stability, and of particular importance are
      oxidative clustered DNA lesions (OCDLs), defined as two or more oxidative lesions
      present within 10 bp of each other. ROS can be produced by exposure of cells to
      exogenous environmental agents including ionizing radiation, light, chemicals,
      and metals. In addition, they are produced by cellular metabolism including
      mitochondrial ATP generation. However, ROS also serve a variety of critical
      cellular functions and optimal ROS levels are maintained by multiple cellular
      antioxidant defenses. Oxidative DNA lesions can be efficiently repaired by base
      excision repair or nucleotide excision repair. If ROS levels increase beyond the
      capacity of its antioxidant defenses, the cell's DNA repair capacity can become
      overwhelmed, leading to the accumulation of oxidative DNA damage products
      including OCDLs, which are more difficult to repair than individual isolated DNA
      damage products. Here we focus on the induction and repair of OCDLs and other
      oxidatively induced DNA lesions. If unrepaired, these lesions can lead to the
      formation of mutations, DNA DSBs, and chromosome abnormalities. We discuss the
      roles of these lesions in human pathologies including aging and cancer, and in
      bystander effects.

PMID- 20060491
TI  - Spatiotemporal characterization of ionizing radiation induced DNA damage foci and
      their relation to chromatin organization.
AB  - DNA damage sensing proteins have been shown to localize to the sites of DNA
      double strand breaks (DSB) within seconds to minutes following ionizing radiation
      (IR) exposure, resulting in the formation of microscopically visible nuclear
      domains referred to as radiation-induced foci (RIF). This review characterizes
      the spatiotemporal properties of RIF at physiological doses, minutes to hours
      following exposure to ionizing radiation, and it proposes a model describing RIF
      formation and resolution as a function of radiation quality and chromatin
      territories. Discussion is limited to RIF formed by three interrelated proteins
      ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and gammaH2AX
      (phosphorylated variant histone H2AX), with an emphasis on the later. This review
      discusses the importance of not equating RIF with DSB in all situations and shows
      how dose and time dependence of RIF frequency is inconsistent with a one to one
      equivalence. Instead, we propose that RIF mark regions of the chromatin that
      would serve as scaffolds rigid enough to keep broken DNA from diffusing away, but
      open enough to allow the repair machinery to access the damage site. We review
      data indicating clear kinetic and physical differences between RIF emerging from
      dense and uncondensed regions of the nucleus. We suggest that persistent RIF
      observed days following exposure to ionizing radiation are nuclear marks of
      permanent rearrangement of the chromatin architecture. Such chromatin alterations
      may not always lead to growth arrest as cells have been shown to replicate these
      in progeny. Thus, heritable persistent RIF spanning over tens of Mbp may reflect
      persistent changes in the transcriptome of a large progeny of cells. Such model
      opens the door to a "non-DNA-centric view" of radiation-induced phenotypes.

PMID- 20060493
TI  - In vitro and whole animal evidence that methylmercury disrupts GABAergic systems
      in discrete brain regions in captive mink.
AB  - The effects of mercury (Hg) on key components of the GABAergic system were
      evaluated in discrete brain regions of captive juvenile male American mink
      (Neovison vison) using in vitro and in vivo (whole animal) experimental
      approaches. In vitro studies on cortical brain tissues revealed that inorganic Hg
      (HgCl(2); IC50=0.5+/-0.2microM) and methyl Hg (MeHgCl; IC50=1.6+/-0.2microM)
      inhibited glutamic acid decarboxylase (GAD; EC 4.1.1.15) activity. There were no
      Hg-related effects on [(3)H]-muscimol binding to GABA(A) receptors
      (IC50s>100microM). HgCl(2) (IC50=0.8+/-0.3microM) but not MeHgCl (IC50>100microM)
      inhibited GABA-transaminase (GABA-T; EC 2.6.1.19) activity. In a whole animal
      study, neurochemical indicators of GABAergic function were measured in brain
      regions (occipital cortex, cerebellum, brain stem, and basal ganglia) of captive
      mink fed relevant levels of MeHgCl (0 to 2microg/g feed, ppm) daily for 89d. No
      effects on GAD activity were measured. Concentration-dependent decreases in
      [(3)H]-muscimol binding to GABA(A) receptors and GABA-T activity were found in
      several brain regions, with reductions as great as 94% (for GABA(A) receptor
      levels) and 71% (for GABA-T activity) measured in the brain stem and basal
      ganglia. These results show that chronic exposure to environmentally relevant
      levels of MeHg disrupts GABAergic signaling. Given that GABA is the main
      inhibitory neurotransmitter in the mammalian nervous system, prolonged
      disruptions of its function may underlie the sub-clinical impacts of MeHg at
      relevant levels to animal health.

PMID- 20060494
TI  - Influence of the dark/light rhythm on the effects of UV radiation in the eyestalk
      of the crab Neohelice granulata.
AB  - Crustaceans are interesting models to study the effects of ultraviolet (UV)
      radiation, and many species may be used as biomarkers for aquatic contamination
      of UV radiation reaching the surface of the Earth. Here, we investigated cell
      damage in the visual system of crabs Neohelice granulata that were acclimated to
      either 12L:12D, constant light, or constant dark, and were exposed to UVA or UVB
      at 12:00h (noon). The production of reactive oxygen species (ROS), antioxidant
      capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO) damage,
      catalase activity, and pigment dispersion in the eye were evaluated. No
      significant differences from the three groups of controls (animals acclimated to
      12L:12D, or in constant light, or not exposed to UV radiation) were observed in
      animals acclimated to 12L:12D, however, crabs acclimated to constant light and
      exposed to UV radiation for 30min showed a significant increase in ROS
      concentration, catalase activity, and LPO damage, but a decrease in ACAP compared
      with the controls. Crabs acclimated to constant darkness and exposed to UV for
      30min showed a significantly increased ROS concentration and LPO damage, but the
      ACAP and catalase activity did not differ from the controls (animals kept in the
      dark while the experimental group was being exposed to UV radiation). Pigment
      dispersion in the pigment cells of eyes of animals acclimated to constant light
      was also observed. The results indicate that UVA and UVB alter specific oxidative
      parameters; however, the cell damage is more evident in animals deviated from the
      normal dark/light rhythm.

PMID- 20060495
TI  - Discovery of high-level tasks in the operating room.
AB  - Recognizing and understanding surgical high-level tasks from sensor readings is
      important for surgical workflow analysis. Surgical high-level task recognition is
      also a challenging task in ubiquitous computing because of the inherent
      uncertainty of sensor data and the complexity of the operating room environment.
      In this paper, we present a framework for recognizing high-level tasks from low
      level noisy sensor data. Specifically, we present a Markov-based approach for
      inferring high-level tasks from a set of low-level sensor data. We also propose
      to clean the noisy sensor data using a Bayesian approach. Preliminary results on
      a noise-free dataset of ten surgical procedures show that it is possible to
      recognize surgical high-level tasks with detection accuracies up to 90%.
      Introducing missed and ghost errors to the sensor data results in a significant
      decrease of the recognition accuracy. This supports our claim to use a cleaning
      algorithm before the training step. Finally, we highlight exciting research
      directions in this area.

PMID- 20060496
TI  - Are newer generation hemoglobin-based oxygen carriers safe: do they offer an
      answer?

PMID- 20060497
TI  - Delivery of amphotericin B nanosuspensions to the brain and determination of
      activity against Balamuthia mandrillaris amebas.
AB  - Amphotericin B was formulated as nanosuspensions to develop a nanoparticulate
      brain delivery system. Nanosuspensions were produced with different surfactant
      solutions by high-pressure homogenization and then characterized by laser
      diffractometry and photon correlation spectroscopy. Before in vitro and in vivo
      testing all nanosuspensions were investigated for protein adsorption by two
      dimensional polyacrylamide gel electrophoresis to predict brain-targeting
      capacities. Selected nanosuspensions were tested for amebicidal activity against
      Balamuthia mandrillaris, an agent of lethal encephalitis. Our results indicate
      that nanosuspensions coated with polysorbate 80 and sodium cholate markedly
      increased drug brain delivery and inhibited the parasite in vitro, though less in
      vivo. From the clinical editor: The antifungal Amphotericin B was formulated as
      nanosuspensions to develop a nanoparticulate brain delivery system. The results
      indicate that nanosuspensions coated with polysorbate 80 and sodium cholate
      markedly increased drug brain delivery and inhibited the parasite in vitro,
      though less in vivo.

PMID- 20060498
TI  - Silver nanoparticles as a safe preservative for use in cosmetics.
AB  - Concern is continuously raised regarding the safety of preservatives, which are
      crucial in most cosmetic preparations. The antimicrobial effects of silver (Ag)
      are well recognized; however, Ag has some limitations as a preservative, such as
      its interference with salts. In this study, we investigated the effects of
      recently synthesized Ag nanoparticles on microorganisms, the permeability of Ag
      nanoparticles in human skin, and the cytotoxicity of Ag nanoparticles in human
      keratinocytes under ultraviolet B irradiation. Ag nanoparticles were found to be
      very stable, and they did not exhibit sedimentation for over 1 year. Ag
      nanoparticles showed sufficient preservation efficacy against mixed bacteria and
      mixed fungi, and did not penetrate normal human skin. At concentrations of 0.002
      0.02 parts per million, Ag nanoparticles had no effect on HaCaT keratinocytes and
      did not enhance ultraviolet B-induced cell death. These results suggest that Ag
      nanoparticles may have potential for use as a preservative in cosmetics. From the
      clinical editor: In this study, the effects of recently synthesized Ag
      nanoparticles were investigated on microorganisms, along with the skin
      permeability and the cytotoxicity in human keratinocytes under UVB-irradiation.
      Ag nanoparticles were found to be very stable, showed sufficient preservation
      efficacy against mixed bacteria and mixed fungi, and did not penetrate normal
      human skin. Ag nanoparticles appear to be suitable for use as a preservative in
      cosmetics.

PMID- 20060499
TI  - Use of latent growth curve models for assessing the effects of darbepoetin alfa
      on hemoglobin and fatigue.
AB  - BACKGROUND: The relationship between darbepoetin alfa and fatigue in chemotherapy
      induced anemia (CIA) patients is complex because of patients receiving
      transfusions and the mediating effect of hemoglobin. Latent growth models (LGMs)
      were used to examine simultaneously relationships among drug exposure, fatigue
      outcomes, covariates, and mediating factors. METHODS: Data from four CIA studies
      (AMG 20010145: small cell lung cancer, n=547; AMG 980297: lung cancer, n=288; AMG
      20000161: lymphoproliferative malignancies, n=339; AMG 20030232: non-myeloid
      malignancies, n=320) were analyzed separately. Patients reported fatigue using
      the FACT-Fatigue. The effect of darbepoetin alfa on FACT-F changes mediated
      through hemoglobin changes was examined with LGMs controlling for transfusions,
      age, sex, baseline ECOG performance status, and health status (EQ-5D VAS). Model
      fit was assessed using multiple indices including the comparative fit index
      (CFI). RESULTS: Darbepoetin alfa increased hemoglobin levels which were
      associated with decreases in fatigue. Increases in hemoglobin were statistically
      significantly (p<0.05) related to decreases in fatigue in the studies (AMG
      20030145: beta=0.28; AMG 980297: beta=0.46; AMG 20000161: beta=0.59; and AMG
      20030232: beta=0.39). Darbepoetin alfa statistically significantly increased
      hemoglobin (AMG 20010145:beta=0.50, AMG 980297:beta=0.53, AMG 20000161:beta=0.47,
      and AMG 20030232:beta=0.30) while controlling for covariates. Model fit was
      acceptable (CFI> or =0.89) in all studies. CONCLUSIONS: Results indicate LGMs may
      be a valuable statistical method for modeling complex relationships among
      clinical and patient reported outcomes. A statistically significant effect of
      darbepoetin alfa on fatigue change through hemoglobin change occurred across four
      studies, after modeling the effects of transfusions, age, sex, EQ-5D VAS and
      ECOG.

PMID- 20060500
TI  - The use of minimization in clinical trials.
AB  - Since its introduction in 1974 the use of the term Minimization has been
      broadened to include other algorithms. All algorithms use patient characteristics
      to determine the assignment that produces the best overall balance between
      treatment groups. They differ in whether or not they use all of the data from
      each previously assigned subject to assign subsequent subjects so the methods are
      classified as complete or partial minimization. PubMed, Citation Index and
      Cochrane searches determined the frequency of articles using these types of
      minimization and a subset was selected for detailed review regarding the adequacy
      of the usage and reporting of minimization. In the past 10 years usage has
      increased three fold over the previous decade but is still less than 2% of
      clinical trials. None of the studies makes maximum use of minimization and they
      are not following good reporting practices. Concerns about the use of
      minimization have involved selection bias and statistical analysis. Several
      modifications to minimization are suggested to reduce the possibility of
      selection bias so that adding randomization will rarely be required. Separating
      primary and secondary analyses can avoid the statistical problems that
      minimization poses. The two types of analyses are distinguished by opposite
      limiting signs, providing reliable, simplified statistical results. This will
      improve data utilization and make clinical trials more reproducible. Minimization
      should be the method of choice in assigning subjects in all clinical trials.

PMID- 20060501
TI  - Population structure of Glossina palpalis gambiensis (Diptera: Glossinidae)
      between river basins in Burkina Faso: consequences for area-wide integrated pest
      management.
AB  - African animal trypanosomosis is a major obstacle to the development of more
      efficient and sustainable livestock production systems in West Africa. Riverine
      tsetse species such as Glossina palpalis gambiensis Vanderplank are their major
      vectors. A wide variety of control tactics is available to manage these vectors,
      but their elimination will only be sustainable if control is exercised following
      area-wide integrated pest management (AW-IPM) principles, i.e. the control effort
      is targeting an entire tsetse population within a circumscribed area. In the
      present study, genetic variation at microsatellite DNA loci was used to examine
      the population structure of G. p. gambiensis inhabiting two adjacent river
      basins, i.e. the Comoe and the Mouhoun River basins in Burkina Faso. A remote
      sensing analysis revealed that the woodland savannah habitats between the river
      basins have remained unchanged during the last two decades. In addition, genetic
      variation was studied in two populations that were separated by a man-made lake
      originating from a dam built in 1991 on the Comoe. Low genetic differentiation
      was observed between the samples from the Mouhoun and the Comoe River basins and
      no differentiation was found between the samples separated by the dam. The data
      presented indicate that the overall genetic differentiation of G. p. gambiensis
      populations inhabiting two adjacent river basins in Burkina Faso is low
      (F(ST)=0.016). The results of this study suggest that either G. p. gambiensis
      populations from the Mouhoun are not isolated from those of the Comoe, or that
      the isolation is too recent to be detected. If elimination of the G. p.
      gambiensis population from the Mouhoun River basin is the selected control
      strategy, re-invasion from adjacent river basins may need to be prevented by
      establishing a buffer zone between the Mouhoun and the other river basin(s).

PMID- 20060503
TI  - Identification of two novel Trichomonas vaginalis eif-5a genes.
AB  - The eukaryotic translation initiation factor 5A (eIF-5A) is highly conserved and
      is the only protein that is known to contain the unique and essential amino acid
      residue hypusine. Synthesis of hypusine is essential for the function of eIF5A in
      eukaryotic cell proliferation and survival. In this study, we identified two
      novel eukaryotic translation initiation factor 5A (eIF-5A) genes in Trichomonas
      vaginalis. The tveif-5a1 and tveif-5a2 putative genes were localized in different
      contigs, both containing ORFs encoding proteins of 168 amino acids that share
      high sequence identity with eIF-5A sequences from other eukaryotic organisms. A
      phylogenetic tree constructed with TveIF-5A1 and TveIF-5A2 from T. vaginalis and
      13 other eIF-5A sequences of eukaryotic and archaebacterial origin revealed that
      both trichomonal TveIF-5As show the highest degree of similarity to bacteria.
      Using an anti-TveIF-5A antibody, we detected two protein bands and spots of 19
      and 20kDa with isoelectric points (pI) of 5.2 and 5.5, respectively, by one and
      two-dimensional Western blot assays. In addition, we used reverse transcription
      polymerase chain reaction (RT-PCR) to demonstrate that both of these tveif-5a
      genes are expressed in T. vaginalis. Immunofluorescence assays showed that the
      TveIF-5A protein was dispersed throughout the parasite cytoplasm. In conclusion,
      T. vaginalis has two eif-5a genes, and both genes are expressed as highly
      conserved proteins of 19kDa, which are localized in the cytoplasm of this
      parasite.

PMID- 20060502
TI  - Population structure of Pneumocystis jirovecii isolated from immunodeficiency
      virus-positive patients.
AB  - Pneumocystis jirovecii pneumonia (PcP) is an important opportunistic infection
      among immunocompromised patients. Genetic characterization of P. jirovecii
      isolated from HIV-positive patients, based on identification of multiple
      nucleotide sequences at eight distinct loci, was achieved by using PCR with DNA
      sequencing and RFLP. The present study showed that the mitochondrial large
      subunit rRNA (mtLSU rRNA), the cytochrome b (CYB), the superoxide dismutase
      (SOD), the beta-tubulin (beta-tub), the dihydrofolate reductase (DHFR) and the
      dihydropteroate synthase (DHPS) loci sequences were more variable and therefore
      giving additional information than the thioredoxin reductase (Trr1) and the
      thymidylate synthase (TS) genes. Genotyping at those six most informative loci
      enabled the identification of 48 different P. jirovecii multilocus genotypes
      (MLGs). Significant statistical associations between infecting P. jirovecii
      genotypes and patients' age groups or PcP clinical status were found. Also, mtLSU
      rRNA sequences and specific genotypes from other three loci (CYB, SOD, and DHFR)
      were statistically associated. The results suggested large recombination between
      most P. jirovecii MLGs. However, one MLG occurred at a higher frequency than
      would be expected according to panmictic expectations, suggesting linkage
      disequilibrium and clonal propagation. The persistence of this specific MLG may
      be a consequence of clonal reproduction of this successful genotypic array in a
      P. jirovecii population with epidemic structure. The present study provided the
      description of multiple genomic regions of P. jirovecii, improving the
      understanding of genetic variability and frequency distribution of polymorphic
      genotypes, and exploring the criteria of clonality by testing over-representation
      of MLGs.

PMID- 20060504
TI  - New insights on the spread of Triatoma infestans from Bolivia--implications for
      Chagas disease emergence in the southern cone.
AB  - Triatoma infestans, now eliminated from most of South America by control
      campaigns, has been and still is the main Chagas disease vector due to its
      ability to colonize rural dwellings. The traditional hypothesis put forth to
      explain T. infestans adaptation to the synanthropic environment rests on the
      domestication of wild guinea pigs, one of its natural hosts, by Andean tribes
      about 5000 BC. Here we present two new hypotheses, based on organized human
      social activities. The first involves maize production, storage and distribution
      during the Inca period. Maize granaries could host wild rodent populations that
      would attract sylvatic T. infestans that were later dispersed during maize
      distribution. The second hypothesis is associated with the contemporary Urkupina
      Virgin festival, near Cochabamba, where thousands of pilgrims gather for rituals
      in an area that is part of a sylvatic T. infestans focus, thus favoring the
      contact with the insects and leading to their passive dispersal.

PMID- 20060505
TI  - Mitochondrial localization of human FAD synthetase isoform 1.
AB  - FAD synthetase or ATP:FMN adenylyl transferase (FADS or FMNAT, EC 2.7.7.2) is a
      key enzyme in the metabolic pathway that converts riboflavin into the redox
      cofactor FAD. We face here the still controversial sub-cellular localization of
      FADS in eukaryotes. First, by western blotting experiments, we confirm the
      existence in rat liver of different FADS isoforms which are distinct for
      molecular mass and sub-cellular localization. A cross-reactive band with an
      apparent molecular mass of 60 kDa on SDS-PAGE is localized in the internal
      compartments of freshly isolated purified rat liver mitochondria. Recently we
      have identified two isoforms of FADS in humans, that differ for an extra-sequence
      of 97 amino acids at the N-terminus, present only in isoform 1 (hFADS1). The
      first 17 residues of hFADS1 represent a cleavable mitochondrial targeting
      sequence (by Target-P prediction). The recombinant hFADS1 produced in Escherichia
      coli showed apparent K(m) and V(max) values for FMN equal to 1.3+/-0.7 microM and
      4.4+/-1.3 nmol x min(-1) x mg protein(-1), respectively, and was inhibited by FMN
      at concentration higher than 1.5 microM. The in vitro synthesized hFADS1, but not
      hFADS2, is imported into rat liver mitochondria and processed into a lower
      molecular mass protein product. Immunofluorescence confocal microscopy performed
      on BHK-21 and Caco-2 cell lines transiently expressing the two human isoforms,
      definitively confirmed that hFADS1, but not hFADS2, localizes in mitochondria.

PMID- 20060506
TI  - Neutrophils in rheumatoid arthritis: More than simple final effectors.
AB  - Rheumatoid arthritis is the most common inflammatory joint disease. The
      etiopathogenesis of this condition has been classically explained by a T cell
      driven process. However, recent studies have highlighted the possible
      contribution of neutrophils for the early phases of RA physiopathology. These
      cells are phagocytic leukocytes that play crucial roles in the acute defense
      against pathogens while modulating the function of other immune cells and
      contributing to the perpetuation of an initial inflammatory response. The herein
      article reviews recent progresses in the understanding of the immunopathology of
      RA with a special emphasis on the role of neutrophils.

PMID- 20060507
TI  - Infliximab and insulin resistance.
AB  - Insulin resistance is the most important pathophysiologic feature of obesity,
      type 2 diabetes mellitus and prediabetic states. TNF-alpha, a proinflammatory
      cytokine, plays a pivotal role in the pathogenesis of inflammation-associated
      insulin resistance during the course of rheumatic diseases. Therapies aimed at
      neutralizing TNF-alpha, such as the monoclonal antibody infliximab, represent a
      novel approach for 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 non
      diabetic rheumatic patients.

PMID- 20060508
TI  - Mitochondrial sirtuins.
AB  - Sirtuins have emerged as important proteins in aging, stress resistance and
      metabolic regulation. Three sirtuins, SIRT3, 4 and 5, are located within the
      mitochondrial matrix. SIRT3 and SIRT5 are NAD(+)-dependent deacetylases that
      remove acetyl groups from acetyllysine-modified proteins and yield 2'-O-acetyl
      ADP-ribose and nicotinamide. SIRT4 can transfer the ADP-ribose group from NAD(+)
      onto acceptor proteins. Recent findings reveal that a large fraction of
      mitochondrial proteins are acetylated and that mitochondrial protein acetylation
      is modulated by nutritional status. This and the identification of targets for
      SIRT3, 4 and 5 support the model that mitochondrial sirtuins are metabolic
      sensors that modulate the activity of metabolic enzymes via protein deacetylation
      or mono-ADP-ribosylation. Here, we review and discuss recent progress in the
      study of mitochondrial sirtuins and their targets.

PMID- 20060510
TI  - The member of the cyclic di-nucleotide family bis-(3', 5')-cyclic dimeric inosine
      monophosphate exerts potent activity as mucosal adjuvant.
AB  - Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di
      IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized
      with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or
      co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP
      showed significantly higher anti-beta-Gal or OVA immunoglobulin G titres (IgG) in
      sera than those vaccinated with beta-Gal or OVA alone. Furthermore, strong local
      immune responses were also detectable in different mucosal territories, as shown
      by the high levels of beta-Gal-specific secretory IgA (sIgA). The analysis of the
      antigen-specific IgG isotypes in sera, together with the profiles of the
      cytokines and chemokines secreted by lymphocytes from vaccinated animals showed
      that the use of c-di-IMP resulted in stimulation of a mixed T(H)1/T(H)2/T(H)17
      response. Mucosal immunization of C57BL/6 mice with OVA using c-di-IMP as
      adjuvant also led to the stimulation of strong in vivo CTL responses (i.e., 60%
      of antigen-specific lysis) [corrected].Our results demonstrated that the novel
      compound c-di-IMP exhibits strong adjuvant properties when co-administered with
      an antigen by the mucosal route, thereby representing a promising candidate
      adjuvant for the development of mucosal vaccination strategies.

PMID- 20060509
TI  - On the biomechanical function of scaffolds for engineering load-bearing soft
      tissues.
AB  - Replacement or regeneration of load-bearing soft tissues has long been the
      impetus for the development of bioactive materials. While maturing, current
      efforts continue to be confounded by our lack of understanding of the intricate
      multi-scale hierarchical arrangements and interactions typically found in native
      tissues. The current state of the art in biomaterial processing enables a degree
      of controllable microstructure that can be used for the development of model
      systems to deduce fundamental biological implications of matrix morphologies on
      cell function. Furthermore, the development of computational frameworks which
      allow for the simulation of experimentally derived observations represents a
      positive departure from what has mostly been an empirically driven field,
      enabling a deeper understanding of the highly complex biological mechanisms we
      wish to ultimately emulate. Ongoing research is actively pursuing new materials
      and processing methods to control material structure down to the micro-scale to
      sustain or improve cell viability, guide tissue growth, and provide mechanical
      integrity, all while exhibiting the capacity to degrade in a controlled manner.
      The purpose of this review is not to focus solely on material processing but to
      assess the ability of these techniques to produce mechanically sound tissue
      surrogates, highlight the unique structural characteristics produced in these
      materials, and discuss how this translates to distinct macroscopic biomechanical
      behaviors.

PMID- 20060511
TI  - Nicotine hapten structure, antibody selectivity and effect relationships: results
      from a nicotine vaccine screening procedure.
AB  - The aim of the present study was to synthesise and screen a set of novel nicotine
      hapten immunogens used for the treatment of nicotine dependence. In the screening
      process we studied the amount of antibodies generated and their selectivity,
      using ELISA techniques, and their effects on nicotine-induced dopamine release in
      the NAC(shell) of the rat, assessed by in vivo voltammetry. We conclude that even
      small changes such as the linker attachment on the nicotine molecule as well as
      the structure of the linker may greatly influence the selectivity of the
      antibodies and the central neurobiological effects of nicotine that are
      considered critical for its dependence producing properties.

PMID- 20060512
TI  - Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in
      the United States.
AB  - OBJECTIVE: We evaluated vitamin D insufficiency in a nationally representative
      sample of women and assessed the role of vitamin supplementation. STUDY DESIGN:
      We conducted secondary analysis of 928 pregnant and 5173 nonpregnant women aged
      13-44 years from the National Health and Nutrition Examination Survey 2001-2006.
      RESULTS: The mean 25-hydroxyvitamin D (25[OH]D) level was 65 nmol/L for pregnant
      women and 59 nmol/L for nonpregnant women. The prevalence of 25(OH)D<75 nmol/L
      was 69% and 78%, respectively. Pregnant women in the first trimester had similar
      25(OH)D levels as nonpregnant women (55 vs 59 nmol/L), despite a higher
      proportion taking vitamin D supplementation (61% vs 32%). However, first
      trimester women had lower 25(OH)D levels than third-trimester women (80 nmol/L),
      likely from shorter duration of supplement use. CONCLUSION: Adolescent and adult
      women of childbearing age have a high prevalence of vitamin D insufficiency.
      Current prenatal multivitamins (400 IU vitamin D) helped to raise serum 25(OH)D
      levels, but higher doses and longer duration may be required.

PMID- 20060515
TI  - Smoking behavior in context: where and when do people smoke?
AB  - Cue-reactivity research in humans has primarily focused on proximal cues, but
      little is known about the role of distal cues, such as environments and
      situations, in cue-reactivity. The aim of this study was to get an overview of
      contexts in which people smoke and to assess the relationship between contexts
      and smoking urges. Moderately addicted Belgian smokers (N = 110) recorded each
      smoked cigarette during four days and described the place and situation and the
      feeling they experienced when starting to smoke. The data demonstrate that
      different contexts were related to differences in the amount of craving and
      enjoyment that was experienced. Finally, differences in (amount of) contexts
      could be predicted by the level of nicotine dependence. These results are
      relevant for conceptualizing and optimizing smoking addiction treatments.

PMID- 20060516
TI  - An investigation of extreme responding as a mediator of cognitive therapy for
      depression.
AB  - Although the efficacy of Cognitive Therapy (CT) for depression is well
      documented, questions remain about the conditions under which CT is maximally
      effective, and the mechanisms by which CT is efficacious. This study examined the
      role of extreme responding (ER) as a mediator and predictor of relapse, as well
      as a predictor of acute treatment outcome. To test mediation, ER of participants
      in CT was compared to ER of participants receiving Behavioral Activation (BA).
      Results indicated that ER was not a mediator of relapse in either condition. Both
      CT and BA showed reductions in depression severity, however neither group showed
      significant changes in ER over the course of treatment. Finally, ER did not
      predict or moderate acute treatment outcome. The implications of these results,
      strengths and limitations of the current study, and future research directions
      are discussed.

PMID- 20060517
TI  - A pilot randomized trial of metacognitive therapy vs applied relaxation in the
      treatment of adults with generalized anxiety disorder.
AB  - Metacognitive Therapy (MCT) and Applied Relaxation (AR) were compared in a pilot
      treatment trial of generalized anxiety disorder (GAD). Twenty outpatients meeting
      criteria for DSM-IV-TR GAD were assessed before treatment, after treatment and at
      6 m and 12 m follow-up. The patients were randomized and treated individually for
      8-12 weekly sessions. There was no drop-out from MCT and 10% at 6 m follow-up
      from AR. At post-treatment and at both follow-up points MCT was superior to AR.
      Standardized recovery rates for MCT at post-treatment were 80% on measures of
      worry and trait-anxiety compared with 10% following AR. At 6 m follow-up recovery
      rates for MCT were 70% on both measures compared with 10% and 20% for AR. At 12 m
      follow-up recovery rates for MCT were 80% (worry) and 60% (trait-anxiety)
      compared with 10% and 20% following AR. The recovery rates for MCT are similar to
      those obtained in an earlier uncontrolled trial (Wells & King, 2006). The effect
      sizes and standardized recovery rates for MCT suggest that it is a highly
      effective treatment.

PMID- 20060513
TI  - Racial/ethnic disparities in obstetric outcomes and care: prevalence and
      determinants.
AB  - Wide disparities in obstetric outcomes exist between women of different
      race/ethnicities. The prevalence of preterm birth, fetal growth restriction,
      fetal demise, maternal mortality, and inadequate receipt of prenatal care all
      vary by maternal race/ethnicity. These disparities have their roots in maternal
      health behaviors, genetics, the physical and social environments, and access to
      and quality of health care. Elimination of the health inequities because of
      sociocultural differences or access to or quality of health care will require a
      multidisciplinary approach. We aim to describe these obstetric disparities, with
      an eye toward potential etiologies, thereby improving our ability to target
      appropriate solutions.

PMID- 20060518
TI  - [Pathophysiology of liver ischemia-reperfusion injury].
AB  - Hepatic ischemia-reperfusion injury is an underlying complication that occurs in
      clinical conditions such as hepatic resection surgery, liver transplantation and
      the states of shock. Such injury has classically been attributed to the joint
      deleterious action of both neutrophils and reactive oxygen species. However,
      there is increasing evidence that T lymphocytes are also key players in the acute
      reperfusion injury of diverse organs. They seem to act mainly by promoting the
      recruitment of inflammatory cells. The purpose of this review is to summarize the
      molecular and cellular mechanisms that participate in the pathophysiology of
      liver reperfusion injury.

PMID- 20060519
TI  - Impaired acquisition of a mirror-reading skill in Alzheimer's disease.
AB  - Several studies using the mirror-reading paradigm have shown that procedural
      learning and repetition priming may be preserved in the early stages of
      Alzheimer's disease (AD) (e.g., Deweer et al., 1994). According to the classical
      interpretation, improved reading time for repeated words is sustained by a
      repetition priming effect, while procedural learning is demonstrated when this
      improvement is also observed for new words. Following Masson (1986), the
      hypothesis tested in the present study was that improved reading of new words
      could also be due to a repetition priming effect rather than to the acquisition
      of a mirror-reading skill. Indeed, because the same letters are presented
      throughout the task, a repetition priming effect for the letters could suffice to
      explain the improvement in performance. To test this hypothesis, we administered
      to 30 healthy young and elderly subjects and to 30 AD patients a new mirror
      reading task in two phases: an acquisition phase comprising pseudo-words
      constructed with one part of the alphabet, and a test phase in which both pseudo
      words constructed with the same part of the alphabet and pseudo-words constructed
      with another part of the alphabet were presented. If the new pseudo-words
      composed with repeated letters were read faster, it would reflect a repetition
      priming effect; if pseudo-words composed of 'new' letters were read faster, it
      would reflect a procedural learning effect. The results show comparable
      repetition priming effects in AD patients and in healthy elderly subjects,
      whereas only healthy subjects showed a procedural learning effect. These results
      suggest, contrary to previous studies, that the learning of a new perceptual
      skill may not always be preserved in AD.

PMID- 20060520
TI  - Heat waves observed in 2007 in Athens, Greece: synoptic conditions,
      bioclimatological assessment, air quality levels and health effects.
AB  - Heat waves are considered to be increasing in frequency and intensity whereas
      they comprise a significant weather-related cause of deaths in several countries.
      Two heat waves occurred in Greece in summer 2007. These severe heat waves are
      assessed by analyzing the prevailing synoptic conditions, evaluating human
      thermal discomfort, through the Heat Load Index (HL), as well as investigating
      its interrelation of air pollutant concentrations, and the daily air quality
      stress index (AQSI), in the greater region of Athens (Attica), Greece.
      Furthermore, the relation of HL values and the number of heatstroke and heat
      exhaustion events recorded in public hospitals operating within the Greek
      National Health System is examined. Data included radiosonde measurements from
      the Athens airport station (LGAT), NCEP/NCAR reanalysis data in order to obtain
      the position of the Subtropical Jet Stream (STJ), GDAS meteorological data for
      back-trajectory calculation, 10-min meteorological data from 10 Hydro
      Meteorological stations and mean hourly values of nitric dioxide (NO(2)), sulphur
      dioxide (SO(2)) and ozone (O(3)) concentrations, measured at 7 different sites,
      for the last 10-day period of June and July 2007. Spearman's rank correlation
      test was used to observe any possible correlation between HL values and air
      pollutant concentrations, and AQSI values. The results demonstrated different
      synoptic characteristics for the heat waves of June and July. In the heat wave of
      June, higher ambient temperatures were recorded and greater HL values were
      calculated. Extreme discomfort conditions were identified in both heat waves
      during both day-time and night-time hours. The air pollution analysis showed poor
      air quality conditions for the heat wave of July, while a significant correlation
      was found between HL values and average hourly concentrations of O(3), NO(2) and
      SO(2). The number of heat-affected patients reported during the June heat wave
      was larger.

PMID- 20060521
TI  - Cadmium exposure in association with history of stroke and heart failure.
AB  - BACKGROUND: It is unclear whether environmental cadmium exposure is associated
      with cardiovascular disease, although recent data suggest associations with
      myocardial infarction and peripheral arterial disease. OBJECTIVE: The objective
      of this study was to evaluate the association of measured cadmium exposure with
      stroke and heart failure (HF) in the general population. METHODS: We analyzed
      data from 12,049 participants, aged 30 years and older, in the 1999-2006 National
      Health and Nutrition Examination Survey (NHANES) for whom information was
      available on body mass index, smoking status, alcohol consumption, and socio
      demographic characteristics. RESULTS: At their interviews, 492 persons reported a
      history of stroke, and 471 a history of HF. After adjusting for demographic and
      cardiovascular risk factors, a 50% increase in blood cadmium corresponded to a
      35% increased odds of prevalent stroke [OR: 1.35; 95% confidence interval (CI):
      1.12-1.65] and a 50% increase in urinary cadmium corresponded to a 9% increase in
      prevalent stroke [OR: 1.09; 95% CI: 1.00-1.19]. This association was higher among
      women [OR: 1.38; 95% CI: 1.11-1.72] than men [OR: 1.30; 95% CI: 0.93-1.79] (p
      value for interaction=0.05). A 50% increase in blood cadmium corresponded to a
      48% increased odds of prevalent HF [OR: 1.48; 95% CI: 1.17-1.87] and a 50%
      increase in urinary cadmium corresponded to a 12% increase in prevalent HF [OR:
      1.12; 95% CI: 1.03-1.20], with no difference in sex-specific associations.
      CONCLUSIONS: Environmental exposure to cadmium was associated with significantly
      increased stroke and heart failure prevalence. Cadmium exposure may increase
      these important manifestations of cardiovascular disease.

PMID- 20060523
TI  - Serum AMH, FSH, and LH levels in PCOS.

PMID- 20060524
TI  - Is compensation "bad for health"? A systematic meta-review.
AB  - OBJECTIVE: There is a common perception that injury compensation has a negative
      impact on health status, and systematic reviews supporting this thesis have been
      used to influence policy and practice decisions. This study evaluates the quality
      of the empirical evidence of a negative correlation between injury compensation
      and health outcomes, based on systematic reviews involving both verifiable and
      non-verifiable injuries. DESIGN: Systematic meta-review (a "review of reviews").
      DATA SOURCES: PubMED, CINAHL, EMBASE, PEDro, PsycInfo, EconLit, Lexis,
      ABI/INFORM, The Cochrane Library, and the AHRQ EPC were searched from the date of
      their inception to August 2008, and hand searches were conducted. REVIEW METHODS:
      Selection criteria were established a priori. Included systematic reviews
      examined the impact of compensation on health, involved adults, were published in
      English and used a range of outcome measures. Two investigators independently
      applied standard instruments to evaluate the methodological quality of the
      included reviews. Data on compensation scheme design (i.e., the intervention) and
      outcome measures were also extracted. RESULTS: Eleven systematic reviews
      involving verifiable and non-verifiable injuries met the inclusion criteria. Nine
      reviews reported an association between compensation and poor health outcomes.
      All of them were affected by the generally low quality of the primary
      (observational) research in this field, the heterogeneous nature of compensation
      laws (schemes) and legal processes for seeking compensation, and the difficulties
      in measuring compensation in relation to health. CONCLUSION: Notwithstanding the
      limitations of the research in this field, one higher quality review examining a
      single compensation process and relying on primary studies using health outcome
      (rather than proxy) measures found strong evidence of no association between
      litigation and poor health following whiplash, challenging the general belief
      that legal processes have a negative impact on health status. Moves to alter
      scheme design and limit access to compensation on the basis that it is "bad for
      health" are therefore premature, as evidence of such an association is unclear.

PMID- 20060525
TI  - Effect of HMG-CoA reductase inhibitors on vascular cell apoptosis: beneficial or
      detrimental?
AB  - Vascular cell apoptosis, an active form of programmed cell death, plays an
      integral role in atherosclerosis and in-stent restenosis after angioplasty, thus
      promoting the precipitation of acute cardiovascular events. Beyond their
      cholesterol-lowering effects, HMG-CoA reductase inhibitors, or statins, have been
      persistently reported to influence the apoptotic process. In this review we
      discuss the effect of statin treatment on vascular cell apoptosis, and therefore
      on atherosclerosis development, plaque rupture and in-stent restenosis, based on
      the results of up-to-date experimental and clinical studies. Lipophilic statins
      have been shown to induce apoptosis in a variety of cell types, including
      vascular smooth muscle cells and endothelial cells, whereas hydrophilic statins
      (rosuvastatin and pravastatin) have not. The clinical importance of statin
      induced apoptosis remains controversial, as it may blunt vascular wall thickening
      in the early stages of atherosclerosis or reduce the neointimal response to
      injury on the one hand, but on the other hand it may also promote destabilization
      of vulnerable plaques precipitating acute cardiovascular events. Current data
      support the initiation of statin treatment early enough to inhibit both the
      formation of atherosclerotic plaques (primary prevention) and in-stent restenosis
      (secondary prevention).

PMID- 20060526
TI  - Computational assessment of the influence of vastus medialis obliquus function on
      patellofemoral pressures: model evaluation.
AB  - A study was performed to evaluate a computational model used to characterize the
      influence of vastus medialis obliquus (VMO) function on the patellofemoral
      pressure distribution. Ten knees were tested in vitro at 40 degrees, 60 degrees
      and 80 degrees of knee flexion with quadriceps loads applied to represent a
      normal VMO, and with the VMO force decreased by approximately 50% to represent a
      weak VMO. The tests were performed with the cartilage intact and with a full
      thickness cartilage lesion centered on the lateral facet of the patella. The
      experimental tests were replicated computationally by applying discrete element
      analysis to a model of each knee constructed from MRI images. Repeated measures
      statistical comparisons were used to compare computational to experimental data
      and identify significant (p<0.05) differences due to the lesion and the applied
      VMO force. Neither the lateral force percentage nor the maximum lateral pressure
      varied significantly between the computational and experimental data. Creating a
      lesion significantly increased the maximum lateral pressure for all comparisons,
      except for the experimental data at 40 degrees. Both computationally and
      experimentally, decrease in the VMO force increased the lateral force percentage
      by approximately 10% for all cases, and each increase was statistically
      significant. The maximum lateral pressure increase was typically less than 10%
      but was still significant for the majority of comparisons focused on the VMO
      strength. The results indicate that computational modeling can be used to
      characterize how varying quadriceps loading influences the patellofemoral force
      and pressure distributions while varying the condition of cartilage.

PMID- 20060527
TI  - Critical beta-values of all coil planet centrifuges.
AB  - I-type, J-type and non-synchronous centrifuges are all coil planet centrifuges.
      Analysing the motion of I-type and J-type centrifuges has advanced the
      understanding of how to manufacture and use these centrifuges. This paper
      analyses the motion of non-synchronous centrifuges producing equations of motion
      that can be applied to all coil planet centrifuges. This has also produced simple
      equations to determine the critical beta-values for any coil planet centrifuge.
      This paper also demonstrates that I-type centrifuges also have 2 critical beta
      values when it was thought that beta-value did not influence the understanding of
      the processes within I-type centrifuges. For the I-type instrument both of these
      critical values are at bobbin radii approaching infinity. In practice this means
      all I-types function within one beta-value range hence the unilateral
      distribution and type/effectiveness of the mixing is consistent. Finally the
      paper shows the influence that the tangential velocity has on the Archimedean
      screw effect and thus the unilateral distribution of the upper and lower phases
      in the columns of coil planet centrifuges. This explains why the maximum
      stationary phase retention in an I-type centrifuge is limited to 50%.

PMID- 20060528
TI  - Chromatographic behaviour of ionic liquid cations in view of quantitative
      structure-retention relationship.
AB  - The availability of ionic liquids (ILs) in wide areas of application often
      results in the requirement on their determination. The attention is also often
      focused on the knowledge of hydrophobicity as it plays a key role in the
      biological effects, in the assessment of environmental risk and in the prediction
      of the fate of chemicals in the environment and of its influence on retention in
      RP HPLC. One can get information regarding hydrophobicity and retention mechanism
      if quantitative structure-retention relationships (QSRRs) are identified. The
      QSRRs were derived for logarithms of retention factors extrapolated to a pure
      water (or aqueous buffer) eluent, log k(w), determined for the pyridinium and
      imidazolium ionic liquid (IL) cations on two C8 (Supelcosil LC-8-DB, Symmetry C8)
      and two C18 (ACE 5 C18, Symmetry C18) stationary phases with isocratic elution by
      a mobile phase consisting of acetonitrile/40 mM phosphate buffer. The analyses of
      ILs were performed at a flow rate of 1 mL min(-1) with UV detection at 218 nm.
      The QSRRs were derived based on the retention parameters determined
      experimentally and the structural descriptors of test analytes from molecular
      modeling. Separations of ILs were obtained with aqueous acetonitrile buffered at
      pH 3.55 mobile phases. The statistically most significant two-parameter QSRR
      regression equations related log k(w) to the solvent accessible surface (SAS) of
      the analytes and the differences in the energies of the highest occupied and the
      lowest unoccupied molecular orbitals (diffHL). These equations were especially
      good in case of columns with the highest carbon loads and larger specific surface
      areas, i.e. Symmetry C18 and Symmetry C8. On the other hand, the column ACE 5 C18
      appeared to produce the best quality separations of the ILs studied. The QSRRs
      derived in the research shed light on the molecular mechanism of HPLC separation
      of ILs and helped to predict their relative separations.

PMID- 20060529
TI  - Pervaporation in chemical analysis.
AB  - Unlike thermal processes such as distillation, pervaporation relies on the
      relative rates of solute permeation through a membrane and is a combination of
      evaporation and gas diffusion. The analytical pervaporation systems consist of a
      membrane module suitable for liquid sample introduction and a vacuum (or a
      sweeping gas) on the permeate side. It has been used in a wide range of
      applications including the analysis of various organic and inorganic compounds,
      and sample concentration. It has been directly interfaced with gas
      chromatography, spectrophotometry, capillary electrophoresis, electrochemical
      detectors, liquid chromatography, and mass spectrometry. A wide range of liquids,
      slurries, and solids samples has been analyzed using these techniques. This
      review highlights the basic principles of the pervaporation and the state of its
      current development as applied to analytical chemistry.

PMID- 20060530
TI  - Adamantyl-functionalized polymer monolith for capillary electrochromatography.
AB  - An adamantyl (ADM)-functionalized monolithic stationary phase was newly
      synthesized by a single-step copolymerization of 1-adamantyl-(alpha
      trifluoromethyl) acrylate, ethylene dimethacrylate, and 2-acrylamido-2-methyl-1
      propanesulfonic acid in order to prevent the peak tailing of basic solutes in
      capillary electrochromatography and was compared with butyl methacrylate (BMA)
      based one. The ADM structure shields the negatively charged groups on the surface
      of monolith from basic solutes, resulting in better peak shapes than BMA-based
      monolithic stationary phase. As the monomers ratio decreased, the monolithic
      column had lower retention and higher column efficiency which was likely due to
      lower phase ratio and smaller globule size of monolith, respectively. The ADM
      functionalized monolithic columns exhibited a good repeatability and
      reproducibility of column preparation with relative standard deviation values
      below 9% in the studied chromatographic parameters.

PMID- 20060531
TI  - Pressurized hot water extraction (PHWE).
AB  - Pressurized hot water extraction (PHWE) has become a popular green extraction
      method for different classes of compounds present in numerous kinds of matrices
      such as environmental, food and botanical samples. PHWE is also used in sample
      preparation to extract organic contaminants from foodstuff for food safety
      analysis and soils/sediments for environmental monitoring purposes. The main
      parameters which influence its extraction efficiency are namely the temperature,
      extraction time, flow rates and addition of modifiers/additives. Among these
      different parameters studied, temperature is described as the most important one.
      It is reported that the extraction of certain compounds is rather dependent on
      pressurized water with different applied temperature. Thus, the stability and
      reduced solubilities of certain compounds at elevated temperatures are
      highlighted in this review. With some modifications, a scaled-up PHWE could
      extract a higher amount of desirable compounds from solid and powdered samples
      such as plant and food materials. The PHWE extracts from plants are rich in
      chemical compounds or metabolites which can be a potential lead for drug
      discovery or development of disease-resistant food crops.

PMID- 20060532
TI  - Development and validation of a liquid chromatography-tandem mass spectrometry
      assay for the simultaneous quantitation of microcystin-RR and its metabolites in
      fish liver.
AB  - A novel method for identification and quantification of microcystin-RR (MC-RR)
      and its metabolites (MC-RR-GSH and MC-RR-Cys) in the fish liver was developed and
      validated. These analytes were simultaneously extracted from fish liver using
      water containing EDTA with 5% acetic acid, followed by a mixed-mode cation
      exchange SPE (Oasis MCX) and subsequently determined by liquid chromatography
      electrospray ionization ion trap mass spectrometry (LC-ESI-ITMS). Extraction
      parameters including volume and pH of eluting solvents, were optimized. Best
      recoveries were obtained by using 10 mL of 15% ammonia solution in methanol. The
      mean recoveries at three concentrations (0.2, 1.0, and 5.0 microg g(-1) dry
      weight [DW]) for MC-RR, MC-RR-GSH and MC-RR-Cys were 93.6-99%, 68.1-73.6% and
      90.0-95.2%, respectively. Method detection limit (MDL) were 4, 7 and 5 ng g(-1)
      DW for MC-RR, MC-RR-GSH and MC-RR-Cys, respectively. Limits of quantification
      (LOQs) for MC-RR, MC-RR-GSH and MC-RR-Cys were calculated to be 10, 18 and 13 ng
      g(-1) DW, respectively. Finally, this method was successfully applied to the
      identification and quantification of MC-RR, MC-RR-GSH and MC-RR-Cys in the liver
      of bighead carp with acute exposure of MCs.

PMID- 20060533
TI  - Mixed-mode solid-phase extraction followed by liquid chromatography-tandem mass
      spectrometry for the determination of tri- and di-substituted organophosphorus
      species in water samples.
AB  - A procedure for the determination of three phosphoric acid diesters, eight
      triesters and triphenylphosphine oxide (TPPO) in water samples is presented.
      Analytes were simultaneously concentrated using a mixed-mode (reversed-phase and
      anionic-exchange) solid-phase extraction (SPE) sorbent and then sequentially
      eluted with methanol (triesters and TPPO) followed by a 20 mM tetrabutylammonium
      hydrogen sulphate (TBAHS) methanolic solution, case of diesters. After that, they
      were determined, in two different runs, by liquid chromatography-electrospray
      ionization-tandem mass spectrometry (LC-ESI-MS/MS), operating the ESI source in
      the positive (triesters and TPPO) and negative (diesters) ionization modes. The
      efficiency of the extraction step varied between 70 and 105%, except in the case
      of tris(2-ethylhexyl) phosphate (TEHP), and it was barely affected by the type of
      water sample. Moreover, low signal suppression effects were noticed in the ESI
      ionization of extracts obtained from different environmental water samples. As a
      result, the standard addition methodology was only required for the accurate
      quantification of tri-substituted organophosphorus (OPs) species in wastewater
      samples. Limits of quantification of the optimized method ranged from 0.2 to 10
      ng L(-1), depending on the sample matrix and the considered compound. The
      analysis of river and wastewater samples confirmed the occurrence of several tri-
      and di-substituted OPs in the aquatic environment, with the highest
      concentrations corresponding to tris(butoxyethyl) phosphate (TBEP) and
      tris(chloropropyl) phosphate (TCPP).

PMID- 20060534
TI  - Enantioseparation of alpha-amino acids on an 18-crown-6-tetracarboxylic acid
      bonded silica by capillary electrochromatography.
AB  - (-)-(18-Crown-6)-2,3,11,12-tetracarboxylic acid-bonded silica was used as the
      chiral stationary phase in capillary electrochromatography (CEC) for
      enantioseparation of some alpha-amino acids. Separation data in CEC were measured
      in mobile phases of varying pH, and composition of methanol and buffer, and
      compared with those in capillary liquid chromatography (CLC). In CEC better
      enantioseparation was generally obtained in the eluent of lower pH, higher buffer
      concentration and intermediate MeOH content, usually at the expense of analysis
      time. CEC showed generally better enantioselectivity and resolutions than CLC for
      the amino acids investigated.

PMID- 20060535
TI  - Low-density extraction solvent-based solvent terminated dispersive liquid-liquid
      microextraction combined with gas chromatography-tandem mass spectrometry for the
      determination of carbamate pesticides in water samples.
AB  - A simple and fast method of low-density extraction solvent-based solvent
      terminated dispersive liquid-liquid microextraction (ST-DLLME) was developed for
      the highly sensitive determination of carbamate pesticides in the water samples
      by gas chromatography-tandem mass spectrometry (GC-MSMS). After dispersing, the
      obtained emulsion cleared into two phases quickly when an aliquot of acetonitrile
      was introduced as a chemical demulsifier into the aqueous bulk. Therefore, the
      developed procedure does not need centrifugation to achieve phase separation. It
      was convenient for the usage of low-density extraction solvents in DLLME. Under
      the optimized conditions, the limits of detection for all target carbamate
      pesticides were in range of 0.001-0.50 ng mL(-1) and the precisions were in the
      range of 2.3-6.8% (RSDs, 2 ng mL(-1), n=5). The proposed method has been
      successfully applied to the analysis of real water samples and good spiked
      recoveries over the range of 94.5-104% were obtained.

PMID- 20060536
TI  - Use of the modified quick easy cheap effective rugged and safe sample preparation
      approach for the simultaneous analysis of type A- and B-trichothecenes in wheat
      flour.
AB  - A suitable extraction and purification method for the simultaneous liquid
      chromatography-mass spectrometry (LC-MS) determination of five mycotoxins, three
      type A, diacetoxyscirpenol (DAS), T-2 toxin (T-2) and HT-2 toxin (HT-2), and two
      type B-trichothecenes, deoxynivalenol (DON) and nivalenol (NIV), has been
      optimised using a modified "Quick Easy Cheap Effective Rugged and Safe"
      (QuEChERS) method. Different solvents were studied in the extraction procedure to
      obtain better recoveries, which ranged from 86 to 108%, using a 85/15 (v/v)
      mixture of methanol/acetonitrile. The values obtained for recovery, repeatability
      and reproducibility of the optimized method are in agreement with Commission
      Directive 2005/26/EC for methods of analysis of Fusarium toxins. Finally, this
      optimized procedure was applied in wheat flour samples commercialized in Spain.

PMID- 20060537
TI  - On-line identification of 4''-isovalerylspiramycin I in the genetic engineered
      strain of S. spiramyceticus F21 by liquid chromatography with electrospray
      ionization tandem mass spectrometry, ultraviolet absorbance detection and nuclear
      magnetic resonance spectrometry.
AB  - LC-hyphenated techniques were applied to the on-line identification of
      isovalerylspiramycin I (isp I), a spiramycin-like macrolide in the crude extract
      of fermentation broth from a genetically engineered strain of S. spiramyceticus
      F21. In the structural characterization of the large molecular secondary
      metabolite of isp I, LC-DAD-UV-ESI-MS(n) analysis played a crucial role, and stop
      flow LC-(1)H NMR measurement, with bitespiramycin used as reference, was a
      valuable complement approach. This rational approach proved to be an efficient
      means for the rapid and accurate structural determination of known microbial
      secondary metabolites, by which targeted isolation of component(s) of interest
      can be subsequently performed for further biological and pharmacological studies
      in drug development.

PMID- 20060538
TI  - Bioconjugation of 32-macrocyclic polyammonium cations-functionalized gold
      nanoparticles with BSA.
AB  - Water-dispersed, spherical, underivatized Au-NPs with particle size less than 5
      nm were synthesized from an aqueous solution of 32-macrocyclic polyammonium
      chloride, [32]ane-(NH(2)(+))(8).8Cl(-) (32-MCPAC) using sodium borohydride
      (NaBH(4)) as the reducing agent. The bioconjugation of the synthesized Au-NPs at
      different pHs (3.6-5.6) with bovine serum albumin (BSA) protein was studied using
      UV-Vis, fluorescence, and Raman spectroscopy. These studies support that the Au
      NPs were incorporated into the protein moiety and bound to it chemically. The
      binding constants (K(b)) and stoichiometries (n) (i.e., the number of Au-NPs
      bound by the proteins) of BSA protein to the Au-NPs at different pHs were
      determined by measuring the quenching of the fluorescence intensity of the
      tryptophan residues of the protein molecules after conjugation. The values for
      K(b) (n) were found to be 1.05 x 10(10) M(-1) (1.66), 2.09 x 10(10) M(-1) (2.30),
      and 1.86 x 10(10) M(-1) (1.75) at pH 3.60, 4.60, and 5.60 for BSA-Au-NPs
      conjugations, respectively. The results show that BSA binds to the Au-NPs
      strongly at pH 4.60, which is equivalent to its isoelectric point (pI 4.6).

PMID- 20060539
TI  - Influence of ferric oxide modification on the properties of copper oxide
      supported on gamma-alumina.
AB  - X-ray diffraction (XRD), Mossbauer spectroscopy, and temperature-programmed
      reduction (TPR) were employed to investigate the dispersion and reduction
      behaviors of the Fe(2)O(3)/CuO/gamma-Al(2)O(3) system. The results indicated
      that: (1) the crystalline CuO particle in the CuO/gamma-Al(2)O(3) samples was
      redispersed during impregnating CuO/gamma-Al(2)O(3) samples with Fe(NO(3))(3)
      solutions; (2) two different dispersion states of surface iron species could be
      observed, i.e., State I corresponding to the iron(III) species located in the D
      layer on the surface of gamma-Al(2)O(3) and State II corresponding to those in
      the C layer. The dispersed states of surface iron(III) species were closely
      related to the iron loading amount; (3) the copper species located in the D layer
      of alumina surface was easily reduced and the copper species located in the C
      layer were more stable, which could be due to the influence of the iron(III)
      species in the different layers; (4) in the NO+CO reaction, the catalytic
      performances were enhanced due to the Cu-Fe synergism and the main active species
      in this system should be the surface-dispersed copper oxide species.

PMID- 20060540
TI  - Nanoporous polymer--clay hybrid membranes for gas separation.
AB  - Nanohybrid organo-inorgano clay mineral-polydimethylsiloxane (PDMS) membranes
      were prepared by the reaction of pure and/or modified natural clay minerals
      (Sepiolite and montmorillonite) with PDMS in hexane, followed by evaporation of
      the solvent at 70 degrees C. The membranes were characterized by means of XRD,
      SEM, ATD-TG and solid state (29)Si magic angle spinning (MAS) and cross
      polarization (CP) CP/MAS NMR. The morphology of the membranes depends on the
      content loading of clay mineral. For low content, the membrane composition is
      homogeneous, with well dispersed nanoparticles of clay into the polymer matrix,
      whereas for higher clay content, the membranes are constituted also of a mixture
      of well dispersed nanoparticles into the polymer, but in the presence of
      agglomerations of small clay particles. Quantitative (29)Si MAS NMR demonstrated
      a strong correlation between the clay content of the membrane and the average
      length of the PDMS chain, indicating that the nanohybrid material is made of clay
      particles covalently linked to the PDMS structure. This is particularly the case
      for Sepiolite with has a high density of Q(2) silanol sites. The separation
      performances of the prepared membranes were tested for CO(2)/CH(4) and O(2)/N(2)
      mixtures. The observed separation factors showed an increase of the selectivity
      in the case of CO(2)/CH(4) in comparison with membranes made from PDMS alone
      under the same conditions.

PMID- 20060541
TI  - Competition between sodium oleate and sodium silicate for a silicate/oleate
      modified magnetite surface studied by in situ ATR-FTIR spectroscopy.
AB  - Attenuated Total Reflection (ATR) IR spectroscopy was utilized to monitor
      adsorption of sodium oleate and sodium silicate onto synthetic magnetite at
      pH=8.5, both individually and in a competitive manner. Oleate was adsorbed within
      a concentration range of 0.01-0.5 mM. It was observed that adsorption of oleate
      increased linearly with increasing concentration of oleate in solution up to a
      concentration of 0.1 mM. The infrared spectrum of oleate showed a broad single
      band at 1535 cm(-1) assigned to the asymmetric stretching vibration of
      carboxylate, implying chemisorption of oleate to the magnetite surface. The
      kinetics of oleate adsorption followed a pseudo first-order reaction with an
      apparent rate constant of k(1)=0.030+/-0.002 min(-1). Competitive adsorption of
      silicate and oleate was performed either by adding silicate solution to a
      magnetite film initially equilibrated with 0.1 mM oleate or adding oleate
      solution to magnetite treated with silicate solutions in the concentration range
      0.1-5 mM. It was shown that silicate, within reasonable time, had only minor
      effect on the amount of oleate already adsorbed on magnetite. On the other hand,
      oleate did not efficiently compete with silicate if the latter substance was
      already adsorbed on the iron oxide.

PMID- 20060542
TI  - Thin liquid film drainage: ionic vs. non-ionic surfactants.
AB  - This paper compares the rate of drainage of thin liquid films (TLF) containing
      ionic surfactants to that of TLF containing non-ionic surfactants. In essence,
      the theory of drainage has been developed for films containing non-ionic
      surfactants, while the validation of the models, based on the theory in the
      literature, has been performed with experiments on TLF with both, non-ionic and
      ionic surfactants, usually in the presence of significant background
      concentrations of electrolyte. Due to the complexity of problem, the dynamic
      effects on the electrical double layer (EDL) during the film drainage have been
      ignored for many years in the literature. These effects were finally treated
      theoretically and the problem solved numerically in a recent work. The new
      theoretical development however has not yet been validated. In addition, the
      differences in the kinetics of thinning of TLF with ionic and non-ionic
      surfactants have not been exposed in the literature until present. This paper is
      dedicated to revealing these differences. Experiments on kinetics of thinning
      were conducted with microscopic planar TLF, containing two non-ionic surfactants
      (tetraethyleneglycol mono-octylether C(8)E(4) and n-dodecyl-D-maltoside
      C(12)G(2)) and two ionic surfactants (sodium dodecylsulfate SDS and
      tetrapentylammonium bromide TPeAB). The TLF with non-ionic surfactants drain
      according to the well-known theories of Scheludko or Radoev-Manev-Ivanov, which
      confirms their validity. On the contrary, TLFs with ionic surfactants drain in
      general at significantly slower rate, as compared to the TLF with non-ionic
      surfactants, when far from equilibrium. When they are close to the equilibrium
      conditions, the former drain according to the theory developed for TLF with non
      ionic surfactants. An analysis of the experimental results, involving the latest
      achievements in the field is performed, indicating the complex behaviour of the
      electrical double layer under dynamic conditions.

PMID- 20060543
TI  - One-step UV lithography for activation of inert hydrocarbon monolayers and
      preparation of protein micropatterns.
AB  - Materials with chemical micropatterned surface have broad applications in many
      fields. In this article, we report a simple one-step UV lithography method to
      activate inert hydrocarbon monolayers for spontaneous formation of water and
      covalently immobilized protein micropatterns on the surface. Two types of
      hydrocarbon monolayers including octadecyltrichlorosilane (OTS) on silicon oxide
      and 1-hexadecene on hydrogen-terminated silicon were studied. It was found that
      after UV modifications, water can form micropatterns spontaneously on both
      surfaces. Furthermore, when protein solutions were used, covalently immobilized
      protein micropatterns can be formed. Our XPS results and controlled reducing
      experiments showed that UV exposure transformed inert monolayers into active
      surfaces with aldehyde groups, which are responsible for the covalent
      immobilization of proteins. The method reported herein can be applied under
      ambient conditions without having a high vacuum system. It can also be extended
      to pattern other biomolecules bearing amine groups.

PMID- 20060544
TI  - Accelerometry in persons with multiple sclerosis: measurement of physical
      activity or walking mobility?
AB  - OBJECTIVE: Motion sensors such as accelerometers have been recognized as an ideal
      measure of physical activity in persons with MS. This study examined the
      hypothesis that accelerometer movement counts represent a measure of both
      physical activity and walking mobility in individuals with MS. METHODS: The
      sample included 269 individuals with a definite diagnosis of relapsing-remitting
      MS who completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ),
      International Physical Activity Questionnaire (IPAQ), Multiple Sclerosis Walking
      Scale-12 (MSWS-12), Patient Determined Disease Steps (PDDS), and then wore an
      ActiGraph accelerometer for 7days. The data were analyzed using bivariate
      correlation and confirmatory factor analysis. RESULTS: The results indicated that
      (a) the GLTEQ and IPAQ scores were strongly correlated and loaded significantly
      on a physical activity latent variable, (b) the MSWS-12 and PDDS scores strongly
      correlated and loaded significantly on a walking mobility latent variable, and
      (c) the accelerometer movement counts correlated similarly with the scores from
      the four self-report questionnaires and cross-loaded on both physical activity
      and walking mobility latent variables. CONCLUSION: Our data suggest that
      accelerometers are measuring both physical activity and walking mobility in
      persons with MS, whereas self-report instruments are measuring either physical
      activity or walking mobility in this population.

PMID- 20060546
TI  - Marine pollution from antifouling paint particles.
AB  - Antifouling paint particles (APP) are generated during the maintenance of boats
      and are shed from abandoned structures and grounded ships. Although they afford a
      highly visible, colourful reflection of contamination in the vicinity of the
      source, little systematic study has been undertaken regarding the distribution,
      composition and effects of APP in the wider marine environment. This paper
      reviews the state of knowledge in respect of APP, with particular emphasis on
      those generated by recreational boatyards. The likely biogeochemical pathways of
      the biocidal and non-biocidal metals in current use (mainly Cu and Zn) are
      addressed in light of recent research and an understanding of the more general
      behaviour of contaminants in marine systems. Analyses of paint fragment
      composites from recreational facilities in the UK reveal chemical compositions
      that are similar to those representing the net signal of the original
      formulations; significantly, dry weight concentrations of Cu and Zn of up to
      about 35% and 15%, respectively, are observed and, relative to ambient dusts and
      sediment, elevated concentrations of other trace metals, like Ba, Cd, Cr, Ni, Pb
      and Sn, occur. These metals leach more rapidly from APP than a painted surface
      due to the greater surface area of pigments and additives exposed to the aqueous
      medium. In suspension, APP are subject to greater and more rapid environmental
      variation (e.g. salinity, pH, dissolved oxygen) than painted hulls, while settled
      APP represent an important source of persistent and degradable biocides to poorly
      circulating environments. Through diffusion and abrasion, high concentrations of
      contaminants are predicted in interstitial waters that may be accumulated
      directly by benthic invertebrates. Animals that feed non-selectively and that are
      exposed to or ingest paint-contaminated sediment are able to accelerate the
      leaching, deposition and burial of biocides and other substances, and represent
      an alternative vehicle for contaminant entry into the marine foodchain. Clearly,
      an extensive understanding of biocide behaviour on painted surfaces is not
      sufficient for predictive or management purposes regarding APP. Greater caution
      is required by boaters and boatyards during the removal and disposal of solid
      wastes, and more awareness or stricter enforcement of relevant codes of practice
      or legislation is recommended.

PMID- 20060545
TI  - Asymmetric dimethylarginine (ADMA) as a possible risk marker for ischemic stroke.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) affects vascular function by
      blocking nitric oxide synthesis. We examined the relationship of ADMA
      concentration to vascular risk factors in subjects who have undergone annual
      medical check-up. METHODS: ADMA concentration, lipid profile and vascular risk
      factors were assessed during an annual medical examination in 116 subjects (mean
      age 58.7years). Univariate and multivariate analyses were carried out to assess
      factors associated with ADMA concentration. ADMA concentration was also assessed
      in 50 age-matched patients with ischemic stroke. RESULTS: Mean serum ADMA
      concentration was significantly higher in the ischemic stroke patients than the
      medical check-up subjects (0.461+/-0.076 versus 0.433+/-0.056mumol/l; P=0.022).
      Univariate analysis showed that ADMA concentration in the medical check-up
      subjects was significantly associated with age, hypertension, dyslipidemia,
      fasting blood glucose, total and LDL cholesterol concentrations. Multiple
      stepwise linear regression analysis showed that hypertension (beta=0.25, P=0.008)
      and dyslipidemia (beta=0.19, P =0.048) were significant independent determinants
      of ADMA concentration. ADMA concentration increased progressively with number of
      vascular risk factors, with a significant (P=0.001) difference between subjects
      with no risk factors and subjects with > or =2 risk factors. CONCLUSIONS: Serum
      ADMA concentration was significantly associated with vascular risk factors in
      subjects undergoing routine medical check-up. ADMA concentration warrants further
      examination as a possible marker of future development of ischemic stroke.

PMID- 20060547
TI  - [Autopsy in clinical oncology: is it in crisis?].

PMID- 20060548
TI  - [MRI sequences for detection of neurovascular conflicts in patients with
      trigeminal neuralgia and predictive value for characterization of the conflict
      (particularly degree of vascular compression)].
AB  - BACKGROUND AND PURPOSE: A long-term study of the results on trigeminal neuralgia
      (TN) after microsurgical vascular decompression (Kaplan-Meier curves at 20 years)
      showed that cure was achieved in 88.1 % of the patients with a neurovascular
      compression (NVC) producing a large groove on the nerve (Grade III), 78.3 % of
      the patients with a NVC with nerve distortion or displacement (Grade II), and
      58.3 % of the patients with a NVC with simple contact on the nerve (Grade I).
      Therefore, preoperative visualization of the NVC by MRI and determination of its
      grading are important for the therapeutic decision. In this study, we
      investigated the predictive value of MRI for detecting and assessing the degree
      of vascular compression in trigeminal neuralgia. METHODS: The study included 91
      consecutive patients with a preoperative MRI (1.5 Testa) using 3D T2-weighted and
      angio-MR-TOF. NVC prediction and the degree of compression made by an independent
      observer were correlated with surgical data. RESULTS: Eighty of the 91 patients
      had a NVC on MRI, but 83 (91.2 %) patients showed a NVC at surgical exploration
      (eight patients had no NCV). Thus, the sensitivity of imaging in detecting a NVC
      on the symptomatic nerves was 96 % (80/83) and the specificity 100 % (8/8). In
      addition, imaging analysis predicted the responsible vessel in 88.7 % (71/80) of
      the cases and characterized the degree of NVC in 85 % (68/80). The Kappa
      coefficient (KC) for prediction of the NVC degree was 0.795 for arterial and
      venous compressions together (p<0.01; 95 % confidence interval, 0.71-0.88). The
      CK was 0.758 (p<0.01, good agreement) for grade I, 0.787 (p<0.01, good agreement)
      for grade II and 0.824 (p<0.01, excellent agreement) for grade III. CONCLUSIONS:
      High-resolution 3D T2-weighted imaging in combination with angio-MR-TOF is a
      reliable technique for detecting NVC and predicting the degree of the compression
      in NVC.

PMID- 20060549
TI  - [Aneurismal subarachnoid hemorrhage in the elderly subject. Should this patient
      participate in a randomized clinical trial?].

PMID- 20060550
TI  - The C-terminal zinc finger domain of Arabidopsis cold shock domain proteins is
      important for RNA chaperone activity during cold adaptation.
AB  - Among the four cold shock domain proteins (CSDPs) identified in Arabidopsis
      thaliana, it has recently been shown that CSDP1 harboring seven CCHC-type zinc
      fingers, but not CSDP2 harboring two CCHC-type zinc fingers, function as a RNA
      chaperone during cold adaptation. However, the structural features relevant to
      this differing RNA chaperone activity between CSDP1 and CSDP2 remain largely
      unknown. To determine which structural features are necessary for the RNA
      chaperone activity of the CSDPs, the importance of the N-terminal cold shock
      domain (CSD) and the C-terminal zinc finger glycine-rich domains of CSDP1 and
      CSDP2 were assessed. The results of sequence motif-swapping and deletion
      experiments showed that, although the CSD itself harbored RNA chaperone activity,
      the number and length of the zinc finger glycine-rich domains of CSDPs were
      crucial to the full activity of the RNA chaperones. The C-terminal domain itself
      of CSDP1, harboring seven CCHC-type zinc fingers, also has RNA chaperone
      activity. The RNA chaperone activity and nuclei acid-binding property of the
      native and chimeric proteins were closely correlated with each other.
      Collectively, these results indicate that a specific modular arrangement of the
      CSD and the zinc finger domain determines both the RNA chaperone activity and
      nucleic acid-binding property of CSDPs; this, in turn, contributes to enhanced
      cold tolerance in plants as well as in bacteria.

PMID- 20060551
TI  - Evaluation of enzyme-linked immunosorbent assay using milk samples as a potential
      screening test of bovine tuberculosis of dairy cows in Korea.
AB  - An enzyme-linked immunosorbent assay (ELISA) using bulk tank milk samples was
      evaluated as a screening test for bovine tuberculosis (TB), a contagious chronic
      disease of cattle. An ELISA with MPB70, a major antigen of Mycobacterium bovis
      was performed using paired sets of milk and sera samples from 33 tuberculin
      positive and 43 tuberculin-negative cattle. Anti-MPB70 antibodies were detected
      in milk samples and there was a significant correlation between seroreactivities
      of milk and sera samples (R(2)=0.83). Using the tuberculin skin test as the
      reference test, the sensitivities of ELISA using milk and sera samples were 87.8%
      and 81.8%, respectively, and the specificities were 97.7% and 100%, respectively.
      In the screening test using bulk tank milk samples from 931 dairy herds in
      Whasung, Gyeonggi-do, Korea, the positive rate for anti-MPB70 antibody was 4.5%
      (42/931) and the tuberculin-positive rate was 2.8% (26/931). Individual milk
      samples (n=253) were collected from randomly selected 8 problematic and 3
      negative herds (positive and negative in the screening test by MPB70 ELISA using
      bulk tank milk samples, respectively) and tested by MPB70 milk ELISA. In the
      problematic herds, positive rates were 10.5% (20/190) for anti-MPB70 antibodies
      in milk ELISA and 2.1% (4/190) in the tuberculin skin test. More than one dairy
      cows were positive by milk ELISA among the problematic herds, and all tuberculin
      positive dairy cows were positive in the milk ELISA. Further, no positive cows
      were detected in negative herds both by milk ELISA and tuberculin skin test.
      These results suggest that an ELISA, using bulk tank milk samples, might be a
      potential efficient screening test for bovine TB of dairy cows.

PMID- 20060552
TI  - Adrenal ganglioneuromas: a 10-year experience in a Chinese population.
AB  - BACKGROUND: Adrenal ganglioneuroma (GN) is extremely rare. The present study is
      to describe the largest series of this adrenal tumor treated in a single medical
      center to our knowledge. METHODS: Clinical details, radiologic, laboratory, and
      pathologic findings as well as follow-up data were analyzed retrospectively in 17
      patients with incidentally discovered adrenal GN who received operative resection
      at a tertiary referral hospital in eastern China between June 1999 and June 2009.
      RESULTS: The mean age of the 17 GN patients was 39.2 years (range, 7-72;
      male:female ratio, 1:2.4), of whom 13 patients had unilateral GN on the right
      side, and the remaining 4 on the left side. None of the 17 tumors was hormonally
      active. Only 6 of the 17 GN cases were diagnosed as benign nerve cell tumors by
      computed tomography or magnetic resonance imaging before operation. Treatment
      consisted of open unilateral adrenalectomy in 9 patients and laparoscopy in 8
      patients. The mean pathologic size of the adrenal GNs was 6.3 +/- 3.1 cm (range,
      1.0-13.0). Ultrastructural examination provided additional support for confirming
      the diagnosis. CONCLUSION: Although there have been some clues for radiologic
      diagnosis of adrenal GN, pre-operative mis- and maldiagnosis are not infrequent.
      We recommend that complete operative resection should be considered once
      malignancy cannot be excluded by pre-operative evaluation. Laparoscopic
      adrenalectomy is a reasonable option at least for tumors < or =7 cm.

PMID- 20060553
TI  - Pathophysiology and treatment of the systemic inflammatory response syndrome from
      the perspective of evolutionary medicine.

PMID- 20060554
TI  - DNA crunching by a viral packaging motor: Compression of a procapsid-portal
      stalled Y-DNA substrate.
AB  - Many large double-stranded DNA viruses employ high force-generating ATP-driven
      molecular motors to package to high density their genomes into empty procapsids.
      Bacteriophage T4 DNA translocation is driven by a two-component motor consisting
      of the procapsid portal docked with a packaging terminase-ATPase. Fluorescence
      resonance energy transfer and fluorescence correlation spectroscopic (FRET-FCS)
      studies of a branched (Y-junction) DNA substrate with a procapsid-anchoring
      leader segment and a single dye molecule situated at the junction point reveal
      that the "Y-DNA" stalls in proximity to the procapsid portal fused to GFP.
      Comparable structure Y-DNA substrates containing energy transfer dye pairs in the
      Y-stem separated by 10 or 14 base pairs reveal that B-form DNA is locally
      compressed 22-24% by the linear force of the packaging motor. Torsional
      compression of duplex DNA is thus implicated in the mechanism of DNA
      translocation.

PMID- 20060555
TI  - Characterization of cytoplasmic motifs important in rhesus rhadinovirus gB
      processing and trafficking.
AB  - Rhesus monkey rhadinovirus (RRV) is highly related to Kaposi's sarcoma-associated
      herpesvirus (KSHV), a human gamma-herpesvirus etiologically-linked with several
      cancers. Glycoprotein B (gB) homologues are encoded by all herpesviruses and play
      a role in virus attachment, entry, and in egress. We have found that RRV gB, like
      KSHV gB, is cleaved at a consensus furin cleavage site and is modified by both N
      linked and O-linked glycosylation. Mutagenesis of three tyrosine- based
      trafficking motifs, a diacidic tyrosine motif, and a di-lucine motif in the
      cytoplasmic region revealed a role for these sequences in both ER export and
      endocytosis from the plasma membrane. These experiments provide a basis for
      further experiments looking at gB incorporation and role in gamma-herpesvirus
      assembly and egress.

PMID- 20060556
TI  - Characterization of the rhesus fibromatosis herpesvirus MARCH family member rfK3.
AB  - Retroperitoneal fibromatosis-associated herpesvirus (RFHV) is a gamma-herpesvirus
      of macaques that is closely related to Kaposi's sarcoma-associated herpesvirus
      (KSHV). Herein, we present characterization of the K3 gene from RFHV, a homologue
      of the KSHV K3 and K5 genes. Like the KSHV proteins, kK3 and kK5, the rfK3
      protein decreases cell surface MHC I levels. Similar to kK5, rfK3 also modulates
      ICAM-1, but not another kK5 target, B7.2. Inhibitors of dynamin or mutations in
      the rfK3 RING-CH E3 ubiquitin ligase domain block cellular target regulation,
      implicating a ubiquitin-dependent, endocytosis-mediated mechanism for target down
      regulation and degradation. Overall, this manuscript presents the first
      characterization of a non-human primate virus MARCH family E3 ubiquitin ligase
      contributing important information about the evolution of immune avoidance
      strategies in primate viruses and paving the way for an animal model examining
      the importance of kK3 and kK5 in vivo.

PMID- 20060557
TI  - Side-stream membrane bioreactors: Influence of stress generated by hydrodynamics
      on floc structure, supernatant quality and fouling propensity.
AB  - This work aims to characterise the impact of hydrodynamics on sludge properties
      and consequently on fouling mechanisms in side-stream membrane bioreactors
      (MBRs). Two side-stream processes which generate very different shear stresses
      are compared, without filtration. This operating mode permits specific
      quantification of the impact of the external loop (and of induced shear stress)
      on floc structure/morphology, supernatant quality and fouling propensity. The
      study shows that low constraints (7 x 10(-3) Pa) generated on submerged side
      stream hollow fibre modules have no significant impact on sludge properties. In
      contrast, high shear stresses (72 Pa) associated with a crossflow configuration
      induce very significant modifications of the mixed liquor which increases its
      fouling propensity (measured in a standard filtration cell). A theoretical
      explanation of the role of turbulence on the floc size distribution is given.
      Based on a Kolmogorov microscale calculation, it seems possible to predict the
      mean floc size reached in both filtration systems, for a given shear stress
      intensity. Disaggregation is characterised by a two-step kinetic: first a short
      term breakage attributed to fragmentation and loss of weak strength bonds, and
      secondly a longer-term breakage probably due to erosion phenomena and removal of
      high strength bonds. Only the second step induces a significant release and an
      accumulation of soluble protein-like substances. Soluble organic matter strongly
      enhances the fouling propensity of the mixed liquor. This seems to be amplified
      by the concentration of protein-like substances. The importance of considering
      the protein and carbohydrate content as well as floc size is also pointed out in
      the paper.

PMID- 20060558
TI  - Anaerobic bioremediation of hexavalent uranium in groundwater by reductive
      precipitation with methanogenic granular sludge.
AB  - Uranium has been responsible for extensive contamination of groundwater due to
      releases from mill tailings and other uranium processing waste. Past evidence has
      confirmed that certain bacteria can enzymatically reduce soluble hexavalent
      uranium (U(VI)) to insoluble tetravalent uranium (U(IV)) under anaerobic
      conditions in the presence of appropriate electron donors. This paper focuses on
      the evaluation of anaerobic granular sludge as a source of inoculum for the
      bioremediation of uranium in water. Batch experiments were performed with several
      methanogenic anaerobic granular sludge samples and different electron donors.
      Abiotic controls consisting of heat-killed inoculum and non-inoculated treatments
      confirmed the biological removal process. In this study, unadapted anaerobic
      granular sludge immediately reduced U(VI), suggesting an intrinsic capacity of
      the sludge to support this process. The high biodiversity of anaerobic granular
      sludge most likely accounts for the presence of specific microorganisms capable
      of reducing U(VI). Oxidation by O(2) was shown to resolubilize the uranium. This
      observation combined with X-ray diffraction evidence of uraninite confirmed that
      the removal during anaerobic treatment was due to reductive precipitation. The
      anaerobic removal activity could be sustained after several respikes of U(VI).
      The U(VI) removal was feasible without addition of electron donors, indicating
      that the decay of endogenous biomass substrates was contributing electron
      equivalents to the process. Addition of electron donors, such as H(2) stimulated
      the removal of U(VI) to varying degrees. The stimulation was greater in sludge
      samples with lower endogenous substrate levels. The present work reveals the
      potential application of anaerobic granular sludge for continuous bioremediation
      schemes to treat uranium-contaminated water.

PMID- 20060559
TI  - Comment on "Measurement of additional shear during sludge conditioning and
      dewatering'" by Banu Ormeci and Ayaz Ahmad, Water Research 43 (2009) 3249-3260.

PMID- 20060560
TI  - Mathematical model for analysis of recirculating vertical flow constructed
      wetlands.
AB  - The recirculating vertical flow constructed wetland (RVFCW) was developed for the
      treatment of domestic wastewater (DWW). In this system, DWW is applied to a
      vertical flow bed through which it trickles into a reservoir located beneath the
      bed. It is then recirculated back to the root zone of the bed. In this study, a
      compartmental model was developed to simulate the RVFCW. The model, which
      addresses transport and removal kinetics of total suspended solids, 5-day
      biological oxygen demand and nitrogen, was fitted to kinetical results obtained
      from pilot field setups and a local sensitivity analysis was performed on the
      model parameters and operational conditions. This analysis showed that after 5h
      of treatment water quality is affected more by stochastic events than by the
      model parameter values, emphasizing the stability of the RVFCW system to large
      variations in operational conditions. Effluent quality after 1h of treatment,
      when the sensitivity analysis showed the parameter impacts to be largest, was
      compared to model predictions. The removal rate was found to be dependent on the
      recirculation rate. The predictions correlated well with experimental
      observations, leading to the conclusion that the proposed model is a satisfactory
      tool for studying RVFCWs.

PMID- 20060561
TI  - Formation of carbonaceous and nitrogenous disinfection by-products from the
      chlorination of Microcystis aeruginosa.
AB  - Formation of carbonaceous disinfection by-products (C-DBPs), including
      trihalomethanes (THMs), haloacetic acids (HAAs), haloketones (HKs), chloral
      hydrate (CH), and nitrogenous disinfection by-products (N-DBPs), including
      haloacetonitriles (HANs) and trichloronitromethane (TCNM) from chlorination of
      Microcystis aeruginosa, a blue-green algae, under different conditions was
      investigated. Factors evaluated include contact time, chlorine dosages, pH,
      temperature, ammonia concentrations and algae growth stages. Increased reaction
      time, chlorine dosage and temperature improved the formation of the relatively
      stable C-DBPs (e.g., THM, HAA, and CH) and TCNM. Formation of
      dichloroacetonitrile (DCAN) followed an increasing and then decreasing pattern
      with prolonged reaction time and increased chlorine dosages. pH affected DBP
      formation differently, with THM increasing, HKs decreasing, and other DBPs having
      maximum concentrations at certain pH values. The addition of ammonia
      significantly reduced the formation of most DBPs, but TCNM formation was not
      affected and 1,1-dichloropropanone (1,1-DCP) formation was higher with the
      addition of ammonia. Most DBPs increased as the growth period of algal cells
      increased. Chlorination of algal cells of higher organic nitrogen content
      generated higher concentrations of N-DBPs (e.g., HANs and TCNM) and CH,
      comparable DCAA concentration but much lower concentrations of other C-DBPs
      (e.g., THM, TCAA and HKs) than did natural organic matter (NOM).

PMID- 20060562
TI  - Fractionating soluble microbial products in the activated sludge process.
AB  - Soluble microbial products (SMP) are the pool of organic compounds originating
      from microbial growth and decay, and are usually the major component of the
      soluble organic matters in effluents from biological treatment processes. In this
      work, SMP in activated sludge were characterized, fractionized, and quantified
      using integrated chemical analysis and mathematical approach. The utilization
      associated products (UAP) in SMP, produced in the substrate-utilization process,
      were found to be carbonaceous compounds with a molecular weight (MW) lower than
      290 kDa which were quantified separately from biomass-associated products (BAP).
      The BAP were mainly cellular macromolecules with an MW in a range of 290-5000
      kDa, and for the first time were further classified into the growth-associated
      BAP (GBAP) with an MW of 1000 kDa, which were produced in the microbial growth
      phase, and the endogeny-associated BAP (EBAP) with an MW of 4500 kDa, which were
      generated in the endogenous phase. Experimental and modeling results reveal that
      the UAP could be utilized by the activated sludge and that the BAP would
      accumulate in the system. The GBAP and EBAP had different formation rates from
      the hydrolysis of extracellular polymeric substances and distinct biodegradation
      kinetics. This study provides better understanding of SMP formation mechanisms
      and becomes useful for subsequent effluent treatment.

PMID- 20060563
TI  - Effects of dioxin isomers on induction of AhRs and CYP1A1 in early developmental
      stage embryos of medaka (Oryzias latipes).
AB  - The aryl hydrocarbon receptor (AhR) binds to polyaromatic compounds, including
      dioxins, and enhances the expression of several target genes, including drug
      metabolizing cytochrome P450s (CYP1As). Four AhR genes (AhR1b-1, AhR1b-2, AhR2a,
      and AhR2b) were identified in the medaka genome. The molecular machinery involved
      in the dioxin response has been clarified chiefly in mammals, although fish
      models, such as zebrafish (Danio rerio), medaka (Oryzias latipes), and Fundulus,
      are excellent candidates for examining the mechanisms of developmental dioxin
      toxicity. Using these fish models, several experimental studies investigating the
      induced expression of CYP1A1 and AhRs, including functional evaluations by
      2378T4CDD exposure, have been performed. However, few studies have examined the
      exposure to other dioxin isomers and it is not certain whether similar induced
      expressions patterns and toxicity-mediating functions of CYP1A1, AhRs, and AhR
      repressor (AhRR) compare with 2378T4CDD exposure. In this study, we investigated
      the toxicity of 13 dioxin isomers, including 2378T4CDD, and the induced
      expression of AhRs, AhRR, and CYP1A1 (CYP1A1_ORYLA) in the early life stages of
      medaka embryos. After exposure to dioxin isomers for 24-48h, the expression of
      AhR2a and CYP1A1_ORYLA correlated to the dioxin toxicity, and AhRR mRNA was
      widely expressed indicating it modulates AhR activity during the early stages of
      medaka embryos.

PMID- 20060564
TI  - Controlled reduction of red mud waste to produce active systems for environmental
      applications: heterogeneous Fenton reaction and reduction of Cr(VI).
AB  - In this work, controlled reduction of red mud with H(2) was used to produce
      active systems for two different environmental applications, i.e. the
      heterogeneous Fenton reaction and the reduction of Cr(VI). Mossbauer, powder X
      ray diffraction, thermal analyses and scanning electron microscopy analyses
      showed that at different temperatures, i.e. 300, 400, 500 and 600 degrees C, H(2)
      reduces red mud to different phases, mainly Fe(3)O(4), Fe(0)/Fe(3)O(4) and Fe(0).
      These Fe phases are dispersed on Al, Si and Ti oxides present in the red mud and
      show high reactivity towards two environmental applications, i.e. the
      heterogeneous Fenton reaction and the reduction of Cr(VI). Reduction with H(2) at
      400 degrees C showed the best results for the oxidation of the model dye
      methylene blue with H(2)O(2) at neutral pH due to the presence of the composite
      Fe(0)/Fe(3)O(4). The reduced red mud at 500-600 degrees C produced Fe(0) highly
      active for the reduction of Cr(VI) in aqueous medium. Another feature of these
      red mud based system is that after deactivation due to extensive use they can be
      completely regenerated by simple treatment with H(2).

PMID- 20060565
TI  - Transfer kinetics to egg yolk and modeling residue recovered in yolk of readily
      metabolized molecules: polycyclic aromatic hydrocarbons orally administered to
      laying hens.
AB  - The kinetic of transfer into egg yolk of Persistent Organic Pollutants with
      contrasting properties regarding biotransformation and bioaccumulation was
      investigated. Twenty-four Hy line hens, aged 26weeks, were orally administered,
      during 1 or 3 consecutive days, 6mg of a mixture of three PAHs (phenanthrene,
      pyrene, benzo[a]pyrene) in equal amounts (w:w) or 3mg of lindane per kg body
      weight daily. Each day, contaminants were administered 1h after oviposition in
      one gelatin capsule. Eggs were collected daily during the 12d following the first
      dosing. Concentrations of PAHs and their main hydroxylated metabolites in yolk
      were determined using HPLC coupled with fluorimetric detection, while lindane was
      analysed by GC-ED. At the end of the experiment, hens were sacrified and
      preovulatory yolks were collected and weighed. All three PAHs were recovered in
      yolks, mainly as metabolites, indicating an active biotransformation of these
      compounds in hens. Within 10d, PAHs and metabolites concentrations in yolks were
      back to initial values. However, the recovery rate of these compounds to yolk
      calculated over the 12-d experiment, was very low, reaching 0.089%, 0.034% and
      0.006% for Phe, Pyr and B[a]P, respectively. Daily deposition of yolk and of PAHs
      and metabolites were found to be directly proportional, indicating that no
      significant body storage of these PAHs occurred and that they were rapidly
      hydroxylated after ingestion. In contrast, lindane and yolk deposition could not
      be related. Storage of lindane in body fat explains its slower elimination via
      eggs.

PMID- 20060566
TI  - Dramatic enhancement of solar disinfection (SODIS) of wild Salmonella sp. in PET
      bottles by H2O2 addition on natural water of Burkina Faso containing dissolved
      iron.
AB  - Disinfection of surface water containing dissolved iron (0.3 mg L(-1)) at natural
      neutral pH ( approximately 7.5) was carried out via solar disinfection (SODIS)
      treatment in PET bottles with H(2)O(2) (10 mg L(-1)). Wild coliforms and
      Salmonella sp. were monitored for 6 h of sunlight irradiation and 72 h of dark
      post-treatment period. In our conditions, SODIS treatment could not avoid
      Salmonella sp. re-growth during dark storage, meanwhile the addition of 10 mg L(
      1) of H(2)O(2) showed a strong enhancement of the inactivation rate without any
      re-growth of both bacteria. Finally, total coliforms (Escherichia coli included)
      demonstrated to be an inappropriate indicator for monitoring bacterial
      contamination in water during solar disinfection processes.

PMID- 20060567
TI  - Effects of bamboo charcoal and bamboo vinegar on nitrogen conservation and heavy
      metals immobility during pig manure composting.
AB  - Composting is an effective methodology for the treatment of organic waste like
      pig manure (PM) before land application. However, nitrogen loss through NH(3)
      volatilization during the thermophilic phase is one of the major disadvantages of
      composting. The presence of Cu and Zn in compost arising from pig feed additives
      is also an issue. In this study the effects of bamboo charcoal (BC) and bamboo
      vinegar (BV) added to composting piles on nitrogen conservation and immobility of
      Cu and Zn during PM composting was investigated. Total Kjeldahl nitrogen (TKN)
      loss and mobility of Cu and Zn decreased with increased BC addition. TKN loss and
      mobility of Cu and Zn in the treatment with 9% BC at the end of composting
      significantly decreased by 65%, 35% and 39% respectively, as compared to the
      control. Addition of BV further decreased TKN loss. After composting, TKN loss in
      the treatment with 3% BC+0.4% BV was 23% lower than that in the treatment with 9%
      BC. The final results indicated that by adding BC or BC+BV into PM composting is
      an effective method to reduce TKN loss and control the mobility of Cu and Zn.

PMID- 20060568
TI  - Effects of support size and orientation on symmetric gaits in free-ranging
      tamarins of Amazonian Peru: implications for the functional significance of
      primate gait sequence patterns.
AB  - The adoption of a specific gait sequence pattern during symmetrical locomotion
      has been proposed to have been a key advantage for the exploitation of the fine
      branch niche in early primates. Diverse aspects of primate locomotion have been
      extensively studied in technically equipped laboratory settings, but evolutionary
      conclusions derived from these investigations have rarely been verified in wild
      primates. Bridging the gap from the lab to the field, we conducted an actual
      performance determination of symmetrical gaits in two free-ranging tamarin
      species (Saguinus mystax and Saguinus fuscicollis) of Amazonian Peru by analyzing
      high-speed video recordings of naturally occurring locomotor bouts. Tamarins
      arguably represent viable models for aspects of early primate locomotion. We
      tested three specific hypotheses derived from laboratory studies to test for the
      influence of support size and orientation and to gain further insight into the
      functional significance of primate gait sequence patterns: (1) The tamarins
      utilize symmetrical gaits at a higher rate on small supports than on larger ones.
      (2) During symmetrical locomotion on small supports, diagonal sequences are
      utilized at a higher rate than on larger supports. (3) On inclines, diagonal
      sequences are predominantly used and on declines, lateral sequences are
      predominantly used. Our results corroborated hypotheses 1 and 3. We found no
      clear support for hypothesis 2. In conclusion, our results add to the notion that
      primate gait plasticity, rather than uniform adoption of diagonal sequence gaits,
      enabled early primates to accommodate different support types and effectively
      exploit the small branch niche.

PMID- 20060569
TI  - Three-dimensional musculoskeletal kinematics during bipedal locomotion in the
      Japanese macaque, reconstructed based on an anatomical model-matching method.
AB  - Studying the bipedal locomotion of non-human primates is important for clarifying
      the evolution of habitual bipedalism in the human lineage. However, quantitative
      descriptions of three-dimensional kinematics of bipedal locomotion in non-human
      primates are very scarce, due to difficulties associated with measurements. In
      this study, we performed a kinematic analysis of bipedal locomotion on two highly
      trained (performing) Japanese macaques walking on a treadmill at different speeds
      and estimated three-dimensional angular motions of hindlimb and trunk segments,
      based on a model-based registration method. Our results demonstrated a
      considerable degree of axial rotation occurring at the trunk and hip joints
      during bipedal locomotion, suggesting that bipedal locomotion in Japanese
      macaques is essentially three-dimensional. In addition, ranges of angular motions
      at the hip and ankle joints were larger and the knee joint was more flexed in the
      mid-stance phase with increasing speed, indicating that gait kinematics are
      modulated depending on speed. Furthermore, macaques were confirmed to have
      actually acquired, at least to some extent, the energy conservation mechanism of
      walking due to pendular exchange of potential and kinetic energy, but effective
      utilization of this mutual exchange of energy was found to occur only at
      comparatively low velocity. Spring-like running mechanics were probably more
      exploited at higher speed because the duty factor was above 0.5. Fundamental
      differences in bipedal strategy seem to exist between human and non-human primate
      bipedal locomotion.

PMID- 20060570
TI  - Wildlife vulnerability and risk maps for combined pollutants.
AB  - Ecological risk and vulnerability maps can be used to improve the analysis of
      pollutant risks and communication to stakeholders. Often, such maps are made for
      one pollutant at the time. We used the results of wildlife vulnerability
      analysis, a novel trait-based risk assessment approach, to map overall
      vulnerability of habitats in Denmark to various metals and one insecticide. These
      maps were combined with maps of estimated soil concentrations for the same
      compounds divided by their Maximum Permissible Concentrations. This combination
      yielded relative risk maps that can be used to assess where the highest risk
      conditions to wildlife from these individual pollutants in Denmark occur (hot
      spot identification). In order to show how cumulative risk maps can be made, the
      maps of the individual pollutants were combined assuming different mechanisms of
      joint toxicity: no addition, concentration addition, antagonism and synergism.
      The study demonstrated that with an accurate set of geographical and ecological
      data one can use the results of vulnerability analysis to make relevant
      ecological risk maps that show hot spot areas for risks of single or cumulative
      risks from soil pollutants.

PMID- 20060571
TI  - Community response to environmental noise and the impact on cardiovascular risk
      score.
AB  - OBJECTIVE: The objective of our study was to investigate and evaluate the
      relationship between road traffic noise and cardiovascular risk. METHODS: The
      study sample (n=659; 36.9% male, 63.1% female university students, mean age
      22.83+/-1.58 years) included a group exposed to road traffic noise (n=280,
      L(eq,24h)=67+/-2dB(A)) and a control group (n=379, L(eq,24h)=58.7+/-6dB(A)).
      Subjective response was determined by a validated noise annoyance questionnaire.
      The ten year risk of developing a coronary heart disease event was quantified as
      an evaluation of cardiovascular risk (SCORE60, Framingham 10-year risk estimation
      and projection to the age of 60, relative risk SCORE chart). RESULTS:
      Cardiovascular risk scores were significantly higher in the exposed group based
      on the Framingham scores projected to the age of 60, SCORE60 (AOR=2.72 (95%
      CI=1.21-6.15)) and the relative risk SCORE chart (AOR=2.81 (1.46-5.41)).
      CONCLUSIONS: These findings highlight the association between road traffic noise
      and cardiovascular risk.

PMID- 20060572
TI  - Whole blood, serum, and saliva lead concentrations in 6- to 8-year-old children.
AB  - With increasing evidence of adverse health effects of lower lead levels (below
      10microg/dL in whole blood), studies on novel internal dose biomarkers are
      needed. This study aimed at: (1) assessing the lead exposure by measuring this
      element in whole blood (Pb-blood), serum (Pb-serum), and 3 different types of
      saliva: whole (Pb-whole-saliva), submandibular/sublingual (Pb-sub-saliva) and
      parotid saliva (Pb-parotid-saliva); (2) correlating Pb-blood with Pb-serum; and
      (3) relating Pb-blood and Pb-serum with the lead found in the different salivas.
      The study population included 444 children aged 6 to 8 years attending 4
      government schools in the district of Campos Eliseos, in Ribeirao Preto, Sao
      Paulo State, Brazil. Whole blood, serum, parotid, submandibular/sublingual ("sub
      saliva"), and whole saliva were collected in trace element-free tubes. Lead
      concentrations were determined by inductively coupled plasma-mass spectrometry
      (ICP-MS). Median Pb-blood and Pb-serum were 2.1microg/dL and 0.4microg/L,
      respectively. Ten percent of the children had Pb-blood between 4.0 and
      9.4microg/dL. Boys showed higher Pb-blood than girls (2.3 vs. 2.0microg/dL,
      p<0.0003). Lead concentrations in whole, sub, and parotid saliva were 1.7, 1.4,
      and 1.3microg/L, respectively. No significant correlations were found between Pb
      blood and Pb-serum, between Pb-blood and lead in the 3 different salivas, or
      between Pb-serum and Pb-whole-saliva or Pb-sub-saliva. However, there was a weak
      statistically significant correlation between Pb-serum and Pb-parotid-saliva. In
      conclusion, the mean Pb-blood concentration was 2.4microg/dL, with 10% of the
      children exhibiting Pb-blood between 4.0 and 9.4microg/dL. Boys presented higher
      Pb-blood. Results suggest that Pb-blood has no correlation with Pb-serum or lead
      in the 3 different salivas collected here. A weak but statistically significant
      correlation between Pb-serum and Pb-parotid-saliva was found. Our results also
      point to the need for carrying out more studies on sources of exposure and lead
      levels in children in Brazil.

PMID- 20060573
TI  - Asian dust event observed in Seoul, Korea, during 29-31 May 2008: analysis of
      transport and vertical distribution of dust particles from lidar and surface
      measurements.
AB  - In this study, we investigate the transport of dust particles, its vertical
      distribution, and the associated meteorological conditions during an Asian dust
      event that was observed in Seoul, Korea on May 29-31, 2008. This study analyzes
      data from ground-based and space-borne 2-wavelength polarization lidars,
      particulate mass concentrations, and synoptic weather data. Surface
      meteorological station observations of dust phenomena, dust transport model, and
      weather maps consistently show that the dust particles were transported from the
      source regions (Inner Mongolia, Man-Ju, and Ordos areas) to Korea via the
      northeastern part of China. Network observations of the PM(10) concentrations in
      Korea revealed that a majority of the heavy dust particles traveled across South
      Korea from the northwest to the southeast direction with a horizontal scale of
      250-300km and a traveling speed of approximately 40kmh(-1). This extraordinary
      dust event, in terms of its intensity and timing during the year, occurred due to
      the blockage of an unusually intensified low-pressure system in the northeastern
      part of China as well as high-pressure system centered over the Sea of Okhotsk
      and the Kuril Islands. The low values of the particle depolarization ratio
      (delta(532)) (<or=0.05) and color ratio (CR) during the pre-dust period indicate
      the presence of spherical, non-dust, and relatively small particles. The mean
      delta(532) value was approximately 0.123+/-0.069 between altitudes of ground
      approximately 2.8km, and 0.161+/-0.049 for near-surface dust layer (ground
      approximately 1.2km). This value is quite similar to that obtained during the 3
      year SNU-Lidar measurements in Seoul (delta(532) approximately 0.136+/-0.027).
      The value of delta(532) during the 2nd multilayered dust episode ranged between
      0.081 and 0.120 for near-surface dust layers, and between 0.076 and 0.114 for
      elevated dust layers. The CALIPSO measurements of beta(532), delta(532), and CR
      also revealed the presence of dense dust aerosols along the transport route.

PMID- 20060574
TI  - An estimation of the health impact of groundwater pollution caused by dumping of
      chlorinated solvents.
AB  - BACKGROUND: Hazardous waste sites are major environmental concerns, but few
      studies have quantified their expected utility loss on health. OBJECTIVES: To
      evaluate the health impact of groundwater pollution by an electronics
      manufacturing factory, we conducted a health risk assessment based on expected
      utility loss from liver cancer. METHODS: Based on measurements of major
      pollutants, we estimated the likelihood of developing liver cancer after exposure
      to groundwater contamination. All patients with liver cancer between 1990 and
      2005 in the Taiwan Cancer Registry were followed through 2007 using the National
      Mortality Registry to obtain survival function. Quality of life was assessed with
      two cross-sectional surveys, one employing the standard gamble method, and the
      other using the EQ-5D instrument. Quality-adjusted life expectancy (QALE) was
      estimated by multiplying the utility values with survival function under the unit
      of quality-adjusted life year (QALY). The difference of QALE between the cancer
      cohort and the age- and gender-matched reference population was calculated to
      represent the utility loss due to liver cancer. RESULTS: A total of 94,144
      patients with liver cancer were identified. The average utility loss to
      development of liver cancer was 17.5 QALYs. Based on toxicological approach, we
      estimated that groundwater pollution caused 1.7 extra cases of liver cancer, with
      an overall loss of 29.8 QALYs. Based on epidemiological approach, the expected
      annual excess number of liver cancer would be 3.65, which would have been
      accumulated through the years, had the pollution not mitigated. CONCLUSIONS: We
      demonstrated a practical approach for comparative health risk assessment using
      QALY as the common unit. This approach can be used for policy decisions based on
      possible health risks.

PMID- 20060575
TI  - Notch 1 signaling is active in ovarian cancer.
AB  - OBJECTIVE.: Despite advances in chemotherapy and radical surgery, most advanced
      stage ovarian cancer patients die from their disease, highlighting the need for
      the development of novel treatment strategies. The Notch signaling pathway plays
      an important role in cellular differentiation, proliferation and apoptosis. We
      hypothesized that the active form of Notch 1, the Notch 1 intracellular domain
      (NICD), would be overexpressed in ovarian cancer cells and that depletion of NICD
      would lead to growth reduction. METHODS.: Following institutional review board
      approval, NICD expression was analyzed in human ovarian cancer specimens as well
      as the ovarian cancer cell lines OVCAR3, SKOV3, and CaOV3. In addition, the
      effects of Notch 1 depletion on ovarian cancer cell growth were detected by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) growth assay for
      6 days following transfection with siRNA against Notch 1. RESULTS.: Western blot
      analysis revealed abundant NICD expression in all 3 ovarian cancer cell lines, as
      well as in 16 of 21 (76%) human ovarian cancer samples. Following treatment with
      Notch 1 siRNA, expression of NICD was greatly reduced in all three cell lines.
      Furthermore, this depletion of NICD was associated with significant growth
      inhibition of all three ovarian cancer cell lines. CONCLUSIONS.: NICD was
      frequently expressed in ovarian cancer cell lines and human ovarian cancer
      specimens. Importantly, depletion of Notch 1 led to growth inhibition of ovarian
      cancer cells. These findings support the hypothesis that Notch 1 plays a role in
      ovarian cancer proliferation, encouraging the investigation of this pathway as a
      therapeutic target.

PMID- 20060576
TI  - Ovalbumin content in 2009 to 2010 seasonal and H1N1 monovalent influenza
      vaccines.

PMID- 20060577
TI  - Effects of oxygen tension and follicle cells on maturation and fertilization of
      porcine oocytes during in vitro culture in follicular fluid.
AB  - The objective was to investigate the effects of oxygen tension and follicle cells
      (FCs) during in vitro maturation of porcine oocytes in only porcine (Sus scrofa
      domesticus) follicular fluid (pFF), using static and non-static (rotating)
      culture systems, on the nuclear maturation and subsequent in vitro fertilization
      of the oocytes. In the first experiment, cumulus-oocyte complexes (COCs) were
      matured for 48 h in pFF supplemented with (+) or without (-) FCs (5.2x10(6)
      cells/mL), using the static (S) and rotating (R) culture systems (+FC/S, -FC/S,
      +FC/R, and -FC/R) under 5% or 20% O(2). Co-culture with FCs in the static culture
      system (+FC/S) had a detrimental effect on the meiotic competence of oocytes,
      whereas co-culture with FCs in the rotating culture system (+FC/R) increased
      maturation rates. In both culture systems, oxygen tension had no apparent effects
      on meiotic competence of oocytes, irrespective of culture system and FC addition.
      In the second experiment, COCs were matured under 5% or 20% O(2) using the -FC/S
      or +FC/R culture systems and then fertilized. Oxygen tension had no significant
      effects on fertilization parameters, irrespective of the culture system. The
      rotating culture system increased rates of sperm penetration and male pronuclear
      formation and decreased polyspermic fertilization compared with the static
      culture system (P < 0.05). In conclusion, both -FC/S and +FC/R culture systems
      supported meiotic competence, irrespective of oxygen tension. However, the +FC/R
      culture system may be superior to the -FC/S culture system for promoting
      fertilization.

PMID- 20060578
TI  - Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life
      practice (COMPARE): a randomised trial.
AB  - BACKGROUND: Everolimus-eluting and paclitaxel-eluting stents, compared with bare
      metal stents, reduced the risk of restenosis in clinical trials with strict
      inclusion and exclusion criteria. We compared the safety and efficacy of the
      second-generation everolimus-eluting and paclitaxel-eluting stents in real-life
      practice. METHODS: We randomly assigned 1800 consecutive patients (aged 18-85
      years) undergoing percutaneous coronary intervention at one centre to treatment
      with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a
      composite of safety and efficacy (all-cause mortality, myocardial infarction, and
      target vessel revascularisation) within 12 months. Patients were not told which
      stent they had been allocated. Analysis was by intention to treat. The trial is
      registered with ClinicalTrials.gov, number NCT01016041. FINDINGS: Follow-up was
      completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897
      patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the
      paclitaxel-eluting stent group (relative risk 0.69 [95% CI 0.50-0.95], p value
      for superiority=0.02). The difference was attributable to a lower rate of stent
      thrombosis (6 [<1%] vs 23 [3%], 0.26 [0.11-0-64], p=0.002), myocardial infarction
      (25 [3%] vs 48 [5%], 0.52 [0.33-0.84], p=0.007), and target vessel
      revascularisation (21 [2%] vs 54 [6%], 0.39 [0.24-0.64], p=0.0001). Cardiac
      death, non-fatal myocardial infarction, or target lesion revascularisation
      occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%]
      patients in the paclitaxel-eluting stent group, p value for superiority was
      0.005. INTERPRETATION: The everolimus-eluting stent is better than the second
      generation paclitaxel-eluting stent in unselected patients in terms of safety and
      efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents
      should no longer be used in everyday clinical practice. FUNDING: Unrestricted
      grants from Abbott Vascular and Boston Scientific.

PMID- 20060579
TI  - Modulation of p53 gene expression in the intertidal copepod Tigriopus japonicus
      exposed to alkylphenols.
AB  - The copepod, Tigriopus japonicus has been recognized as an excellent marine model
      species for ecotoxicological studies. The present study cloned and characterized
      the p53 gene of this copepod and studied its expression pattern. We discovered
      that p53 expression patterns varied among different developmental stages of the
      copepod, having the highest expression in the adult. Such variation was possibly
      associated with the molting cycle. By using real-time RT-PCR, we further
      investigated the modulatory pattern of the p53 gene in the copepod after exposure
      to three alkylphenols (i.e. nonylphenol, octylphenol, and bisphenol A) which are
      known as endocrine disruption chemicals (EDCs). The results showed that the three
      alkylphenols significantly induced p53 gene expression in the copepod, indicating
      the involvement of p53 in such stress-responses. Thus, the copepod p53 gene
      provides one of the stress-response biomarkers for exposure to EDC-like
      compounds.

PMID- 20060580
TI  - Electroconductive hydrogels: synthesis, characterization and biomedical
      applications.
AB  - Electroconductive hydrogels (ECHs) are composite biomaterials that bring together
      the redox switching and electrical properties of inherently conductive
      electroactive polymers (CEPs) with the facile small molecule transport, high
      hydration levels and biocompatibility of cross-linked hydrogels. General methods
      for the synthesis of electroconductive hydrogels as polymer blends and as polymer
      co-networks via chemical oxidative, electrochemical and/or a combination of
      chemical oxidation followed by electrochemical polymerization techniques are
      reviewed. Specific examples are introduced to illustrate the preparation of
      electroconductive hydrogels that were synthesized from poly(HEMA)-based hydrogels
      with polyaniline and from poly(HEMA)-based hydrogels with polypyrrole. The key
      applications of electroconductive hydrogels; as biorecognition membranes for
      implantable biosensors, as electro-stimulated drug release devices for programmed
      delivery, and as the low interfacial impedance layers on neuronal prostheses are
      highlighted. These applications provide great new horizons for these stimuli
      responsive, biomimetic polymeric materials.

PMID- 20060581
TI  - Review: Adaptation in placental nutrient supply to meet fetal growth demand:
      implications for programming.
AB  - This review considers the hypothesis that adaptations in blood flow, exchange
      surface area and transporter activity enable placental supply capacity to meet
      fetal demand and cause alterations in fetal composition which result in life-long
      programming of homeostatic set points. We consider the components of placental
      supply capacity and describe the predominant changes each of these could impose
      on solute and water exchange across the placenta. We next consider the evidence
      that adaptations in placental nutrient supply to meet the demands of fetal growth
      and development do occur. Evidence from human and mouse studies suggests that
      adaptations occur in regulation of blood flow through the fetoplacental
      circulation, in exchange barrier surface area and in transporter-mediated
      processes for amino acids and calcium. Crucially there appear to be differences
      in the gestational timing of these adaptations. Finally we suggest that each of
      these adaptations could have separate effects on the composition of the fetus.
      These could affect physiological set points in different ways and so programme
      the lifetime responses of the individual.

PMID- 20060582
TI  - Decreased placental methylation at the H19/IGF2 imprinting control region is
      associated with normotensive intrauterine growth restriction but not
      preeclampsia.
AB  - Many genes exhibiting genomic imprinting, parent-of-origin differences in gene
      expression, are involved in regulating placental and fetal growth. The goal of
      the present study was to assess whether abnormal regulation of imprinted genes is
      associated with intrauterine growth restriction (IUGR) and/or preeclampsia (PET).
      METHODS: Genomic DNA was extracted from at least two whole villi samples from
      control (N=22), IUGR (N=13), PET (N=17), and PET+IUGR (N=21) placentas.
      Methylation was assessed using the Illumina GoldenGate Methylation Cancer Panel I
      array and Pyrosequencing and MS-SNuPE assays. RESULTS: The 11p15.5 ICR1
      (associated with H19 and IGF2) methylation showed considerable intra-placental
      variability. Nonetheless, average methylation at this site was significantly
      decreased in normotensive IUGR placentas (p<0.001), but not in any other group.
      Methylation at ICR2 (KvDMR1; associated with CDKN1C and other maternally
      expressed 11p15.5 genes) was not significantly altered in any group and no
      significant changes in expression levels were observed in the genes controlled by
      this region. There were no significant methylation changes observed in any
      candidate imprinted gene evaluated by the Illumina array. LINE-1 methylation, a
      marker of whole genome methylation, was also similar in all groups. CONCLUSIONS:
      Reduced methylation of ICR1 is associated with normotensive IUGR but not IUGR
      associated with preeclampsia, suggesting a different etiology of IUGR in this
      group. A reduction in placental IGF2 could be an adaptive response to restrict
      fetal growth in the presence of abnormal placentation or a response to poor fetal
      growth itself.

PMID- 20060583
TI  - Validation of placental vascular sonobiopsy for obtaining representative
      placental vascular indices by three-dimensional power Doppler ultrasonography.
AB  - OBJECTIVE: Placental vascular sonobiopsy has been proposed for obtaining a
      representative sample of the placental vascular tree when evaluation of the whole
      placenta is not feasible. We tested the hypothesis that placental vascular
      indices from sonobiopsy correlate well with those from the entire placenta.
      METHODS: Three-dimensional power Doppler ultrasound examinations were performed
      in 120 singleton pregnancies at 11-14 weeks' gestation. The VOCAL program was
      used to calculate placental vascularization index (VI), flow index (FI) and
      vascularization flow index (VFI) from stored images of each placenta by whole
      placenta evaluation and placenta vascular sonobiopsy. The mean of each index from
      four spherical sonobiopsies were compared to those from evaluation of the entire
      placenta for their degree of correlation and agreement. RESULTS: The mean VI and
      VFI from the two techniques were similar (13.9 [95% CI 12.3-15.8] versus 14.3
      [95% CI 12.1-17.0], p = 0.62 and 6.1 [95% CI 5.2-7.1] versus 6.1 [95% CI 5.0
      7.4], p = 0.93, respectively) and significantly correlated (Pearson's r = 0.70
      [95% CI 0.60-0.78, p < 0.001] and r = 0.69 [95% CI 0.58-0.77, p < 0.001],
      respectively). The mean FI from the two techniques were significantly different
      (44.5 [95% CI 42.9-46.1] versus 41.3 [95% CI 39.6-43.0], p = 0.001), but
      correlated (r = 0.59 [95% CI 0.46-0.70, p < 0.001]). CONCLUSION: Our findings
      suggest that placenta vascular indices from sonobiopsy have a good correlation
      with those from evaluation of the entire placenta. Sonobiopsy may be a valid
      alternative for evaluation of the placental vascular tree when visualization of
      the entire placenta is not feasible. Measurements of VI and VFI appear to be more
      reliable than FI in sonobiopsy specimen.

PMID- 20060584
TI  - Review: Trophoblast-vascular cell interactions in early pregnancy: how to remodel
      a vessel.
AB  - During the first twenty weeks of human pregnancy, extravillous trophoblasts (EVT)
      colonise the decidua and remodel the uterine spiral arteries as far as the first
      third of the myometrium. This process leads to an irreversible vasodilatation,
      ensuring that maximal blood flow is delivered to the materno-fetal interface at
      an optimal velocity for nutrient exchange. There is accumulating evidence that
      subtle changes in vascular structure precede EVT colonisation; however, full
      physiological transformation is only achieved in the presence of trophoblast.
      This review discusses the mechanisms employed to facilitate arterial dilatation,
      including recent data regarding the contribution of vascular cell apoptosis, the
      importance of elastin catabolism and the source of candidate elastases. It also
      examines how the complex interplay between EVT, endothelial cells, smooth muscle
      cells and decidual leukocytes (macrophages and uterine natural killer cells)
      leads to enhanced receptivity to invasion, vascular cell loss and extracellular
      matrix remodelling.

PMID- 20060585
TI  - Spatio-temporal PLC activation in parallel with intracellular Ca2+ wave
      propagation in mechanically stimulated single MDCK cells.
AB  - Intracellular Ca2+ transients are evoked either by the opening of Ca2+ channels
      on the plasma membrane or by phospholipase C (PLC) activation resulting in IP3
      production. Ca2+ wave propagation is known to occur in mechanically stimulated
      cells; however, it remains uncertain whether and how PLC activation is involved
      in intracellular Ca2+ wave propagation in mechanically stimulated cells. To
      answer these questions, it is indispensable to clarify the spatio-temporal
      relations between intracellular Ca2+ wave propagation and PLC activation. Thus,
      we visualized both cytosolic Ca2+ and PLC activation using a real-time dual
      imaging system in individual Mardin-Darby Canine Kidney (MDCK) cells. This system
      allowed us to simultaneously observe intracellular Ca2+ wave propagation and PLC
      activation in a spatio-temporal manner in a single mechanically stimulated MDCK
      cell. The results showed that PLC was activated not only in the mechanically
      stimulated region but also in other subcellular regions in parallel with
      intracellular Ca2+ wave propagation. These results support a model in which PLC
      is involved in Ca2+ signaling amplification in mechanically stimulated cells.

PMID- 20060586
TI  - An ATP-dependent mechanism mediates intercellular calcium signaling in bone cell
      network under single cell nanoindentation.
AB  - To investigate the roles of intercellular gap junctions and extracellular ATP
      diffusion in bone cell calcium signaling propagation in bone tissue, in vitro
      bone cell networks were constructed by using microcontact printing and self
      assembled monolayer technologies. In the network, neighboring cells were
      interconnected through functional gap junctions. A single cell at the center of
      the network was mechanically stimulated by using an AFM nanoindenter.
      Intracellular calcium ([Ca2+](i)) responses of the bone cell network were
      recorded and analyzed. In the untreated groups, calcium propagation from the
      stimulated cell to neighboring cells was observed in 40% of the tests. No
      significant difference was observed in this percentage when the intercellular gap
      junctions were blocked. This number, however, decreased to 10% in the
      extracellular ATP-pathway-blocked group. When both the gap junction and ATP
      pathways were blocked, intercellular calcium waves were abolished. When the
      intracellular calcium store in ER was depleted, the indented cell can generate
      calcium transients, but no [Ca2+](i) signal can be propagated to the neighboring
      cells. No [Ca2+](i) response was detected in the cell network when the
      extracellular calcium source was removed. These findings identified the
      biochemical pathways involved in the calcium signaling propagation in bone cell
      networks.

PMID- 20060587
TI  - Role of kinin B1 and B2 receptors in memory consolidation during the aging
      process of mice.
AB  - Under physiological conditions, elderly people present memory deficit associated
      with neuronal loss. This pattern is also associated with Alzheimer's disease but,
      in this case, in a dramatically intensified level. Kinin receptors have been
      involved in neurodegeneration and increase of amyloid-beta concentration,
      associated with Alzheimer's disease (AD). Considering these findings, this work
      evaluated the role of kinin receptors in memory consolidation during the aging
      process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and
      18-month-old - mo; n=10 per group) were submitted to an acquisition session,
      reinforcement to learning (24h later: test 1) and final test (7days later: test
      2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance
      responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar
      CAR were obtained among age matched animals from all strains. However, a
      significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/
      2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a
      reduction in the learning process. In test 1, as expected, memory retention
      increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in
      12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session.
      However, 12-month-old-koB2 and all 18-month-old animals did not show an increase
      in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages
      showed a significant improvement in memory (P<0.05) compared to test 1. However,
      12-month-old wt and koB2 mice of all ages showed no difference in memory
      retention. We suggest that, during the aging process, the B1 receptor could be
      involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is
      apparently acting as a neuroprotective factor.

PMID- 20060588
TI  - Protecting children from violence and maltreatment: a qualitative comparative
      analysis assessing the implementation of U.N. CRC Article 19.
AB  - OBJECTIVES: (1) To identify which United Nations Convention on the Rights of the
      Child (CRC) recommended child protection (CP) measures, such as policy, reporting
      systems, and services for child abuse and neglect (CAN) victims, individually or
      in combination, were most important in establishing a basic level of child
      protection in 42 countries; and (2) to assess whether these measures were
      necessary or sufficient to achieve basic child protection in developing and
      industrialized countries. METHOD: Child protection and/or rights expert
      respondents from 42 countries completed a questionnaire on CRC Article 19 (CRC19)
      required CP measures implementation and rated their country's effectiveness in
      implementation, the current level of effectiveness of child protection, and the
      relevance of improvements in child protection since the CRC was adopted in 1989.
      Information from the Committee on the Rights of the Child Concluding
      Observations, as well as UNICEF and WHO indicators on child health and protection
      issues were used to check and supplement responses. Qualitative comparative
      analysis (QCA) was used to identify child protection measure implementation
      effectiveness. RESULTS: Results indicate that child protection judged as
      comparatively more successful among study countries is a result of having the
      following measures in place from two types of social programs: a CP
      infrastructure (legislation plus services) and at least one information-based
      intervention support program. CONCLUSIONS: Fourteen (33%) countries were
      determined to have established at least a basic CP system toward protection of
      children from violence and maltreatment. These countries reported having the
      three required elements described above. The study reinforces the need for
      governments to take a systems approach to child protection, including
      policy/legislation, information-based programs and social services, as well as
      professional training and public awareness raising. The top-ranked countries
      included: Australia, Bahrain, Belgium, Brazil, Canada, Estonia, Germany, Italy,
      Jordan, Lebanon, Malaysia, Republic of Korea, the Russian Federation, and the
      United Kingdom. PRACTICE IMPLICATIONS: Governments need to establish CP systems
      with multiple, well-integrated, effective CP measures as elaborated above,
      working with trained professionals and also raising public awareness to ensure
      successful protection for all children in every country. Partial measures are not
      effective. Further, in addition to establishing, implementing, and evaluating the
      effectiveness of professional interventions, the actual outcomes for children,
      not studied or reported on here, need to be the priority focus for child
      protection going forward.

PMID- 20060589
TI  - Fuel toxicity on Isochrysis galbana and a coastal phytoplankton assemblage:
      growth rate vs. variable fluorescence.
AB  - Laboratory cultures of the flagellate Isochrysis galbana and a coastal
      phytoplankton assemblage were used to assess the feasibility of variable
      fluorescence (F(v)), measured by means of fast repetition rate fluorometry, as
      endpoint to monitor the effect of fuel on microalgae as compared to phytoplankton
      growth rate. Parallel changes in cell size of I. galbana and taxonomic
      composition of the natural assemblage were recorded. The results presented in
      this investigation indicate that F(v) is a suitable endpoint to this aim, due to
      the ease and rapidity of the measurement, ecological relevance and sensitivity.
      The derived effective concentrations provided toxicity thresholds similar to, or
      even lower than concentrations derived from embryo-larval bioassays with marine
      organisms. The lowest calculated EC(10) corresponded to that of the natural
      assemblage, 2.5 microg eq chrysene L(-1), concentration easily exceeded in high
      maritime traffic areas subjected to frequent spillages.

PMID- 20060590
TI  - Chemical and biological properties in the rhizosphere of Lupinus albus alter soil
      heavy metal fractionation.
AB  - To understand better the suitability of white lupin (Lupinus albus L.) for
      phytoremediation of heavy metal-contaminated soils, the effect of its roots on
      chemical and biological properties of the rhizosphere affecting soil metal
      fractionation was studied. Plants were cultivated in two similar soils, with high
      levels of Zn, Cd, Cu and Pb but differing pH values (4.2 and 6.8). In the
      rhizosphere of both soils, its roots induced increases in water-soluble carbon,
      which influenced the fractionation of heavy metals and ultimately their uptake by
      plant roots. In the rhizosphere of the acid soil, the concentrations of 0.1M
      CaCl(2)-extractable Mn, Zn and Cu were lower than in the bulk soil, possibly due
      to their increased retention on Fe (III) hydroxides/oxyhydroxides, while in the
      neutral soil only the Zn concentration was lower. Higher concentrations of heavy
      metals were found in plants growing on the acid soil, reflecting their greater
      availability in this soil. The restricted transfer of heavy metals to the shoot
      confirms the potential role of this species in the initial phytoimmobilisation of
      heavy metals, particularly in neutral-alkaline soils.

PMID- 20060591
TI  - Leaf antioxidant fluctuations and growth responses in saplings of Caesalpinia
      echinata Lam. (brazilwood) under an urban stressing environment.
AB  - We intended to establish how efficient the leaf antioxidant responses of C.
      echinata are against oxidative environmental conditions observed in an urban
      environment and their relations to growth and biomass parameters. Plants were
      grown for 15 months in four sites: Congonhas and Pinheiros, affected by
      pollutants from vehicular emissions; Ibirapuera, affected by high O(3)
      concentrations; and a greenhouse with filtered air. Fifteen plants were quarterly
      removed from each site for analysis of antioxidants, growth and biomass. Plants
      growing in polluted sites showed alterations in their antioxidants. They were
      shorter, had thicker stems and produced less leaf biomass than plants maintained
      under filtered air. The fluctuations in the levels of antioxidants were
      significantly influenced by combined effects of climatic and pollution variables.
      The higher were the antioxidant responses and the concentrations of pollutant
      markers of air contamination in each site the slower were the growth and biomass
      production.

PMID- 20060592
TI  - A fast ruthenium polypyridine cage complex photoreleases glutamate with visible
      or IR light in one and two photon regimes.
AB  - We introduce a new caged glutamate, based in a ruthenium bipyridyl core, that
      undergoes heterolytic cleavage after irradiation with visible light with
      wavelengths up to 532nm, yielding free glutamate in less than 50ns. Glutamate
      photorelease occurs also efficiently following two-photon (2P) excitation at
      800nm, and has a functional cross section of 0.14GM.

PMID- 20060593
TI  - Cu(I) binding properties of a designed metalloprotein.
AB  - The Cu(I) binding properties of the designed peptide C16C19-GGY are reported.
      This peptide was designed to form an alpha-helical coiled-coil but modified to
      incorporate a Cys-X-X-Cys metal-binding motif along its hydrophobic face.
      Absorption, emission, electrospray ionization mass spectrometry (ESI-MS), and
      circular dichroism (CD) experiments show that a 1:1 Cu-peptide complex is formed
      when Cu(I) is initially added to a solution of the monomeric peptide. This is
      consistent with our earlier study in which the emissive 1:1 complex was shown to
      exist as a peptide tetramer containing a tetranuclear copper cluster Kharenko et
      al. (2005) [11]. The presence of the tetranuclear copper center is now confirmed
      by ESI-MS which along with UV data show that this cluster is formed in a
      cooperative manner. However, spectroscopic titrations show that continued
      addition of Cu(I) results in the occupation of a second, lower affinity metal
      binding site in the metallopeptide. This occupancy does not significantly affect
      the conformation of the metallopeptide but does result in a quenching of the
      600nm emission. It was further found that the exogenous reductant tris(2
      carboxyethyl)phosphine (TCEP) can competitively inhibit the binding of Cu(I) to
      the low affinity site of the peptide, but does not interact with Cu(I) clusters.

PMID- 20060594
TI  - Genetic polymorphism in an inflammasome component, cervical mycoplasma detection
      and female infertility in women undergoing in vitro fertilization.
AB  - The inflammasome is an inducible cytoplasmic structure that is responsible for
      production and release of biologically active interleukin-1 (IL-1). A
      polymorphism in the inflammasome component NALP3 has been associated with
      decreased IL-1 levels and increased occurrence of vaginal Candida infection. We
      hypothesized that this polymorphism-induced variation would influence
      susceptibility to infertility. DNA was obtained from 243 women who were
      undergoing in vitro fertilization (IVF) and tested for a length polymorphism in
      intron 2 of the gene coding for NALP3 (gene symbol CIAS1). At the conclusion of
      testing the findings were analyzed in relation to clinical parameters and IVF
      outcome. The frequency of the 12unit repeat allele, associated with maximal
      inflammasome activity, was 62.3% in cases of female infertility vs. 75.6% in
      cases where only the male partner had a detectable fertility problem (p=0.0095).
      Conversely, the frequency of the 7unit repeat allele was 28.9% in those with a
      female fertility problem, 17.0% in women with infertile males and 18.4% in
      idiopathic infertility (p=0.0124). Among the women who were cervical culture
      positive for mycoplasma the frequency of the 7unit repeat was 53.7% as opposed to
      19.5% in those negative for this infection (p<0.0001). We conclude that the CIAS1
      7unit repeat polymorphism increases the likelihood of mycoplasma infection
      associated female infertility.

PMID- 20060596
TI  - Differentially expressed genes associated with Staphylococcus aureus mastitis in
      dairy goats.
AB  - To study gene expression within the mammary glands of dairy goats with mastitis,
      mRNA was collected from milk somatic cells (MSCs) of left udder halves challenged
      with Staphylococcus aureus and right udder halves infused with PBS, as control,
      at different time points (0, 12, 24 and 48h post-infection). Transcriptional
      profiles were investigated using bovine cDNA microarrays; of the total 288
      differentially expressed genes identified with ANOVA analysis (False Discovery
      Rate=0.05, 1.5-fold change), 26, 36 and 16 genes were down-regulated at 12, 24
      and 48h post-infection, respectively, while 60, 141 and 9 genes were up-regulated
      at the same corresponding time points. The expression profiles clearly changed at
      24h post-infection with 177 genes significantly altered, corresponding to a 10
      fold increase of S. aureus bacterial count in milk from infected udders.
      Differential expression of selected genes (CD2BP2, BCAP31, MHCII, FOSL2, MAPK13,
      ILT5 and JUNB) was also confirmed by real-time PCR at the different time points
      considered, showing high correlation with the microarray measurements and high
      reliability of the microarray analyses. The most readily inducible classes of
      genes in caprine MSCs infected with S. aureus were pro-inflammatory cytokines,
      chemokines and their receptors; IL-1alpha, lymphotoxin alpha, granulocyte
      chemotactic protein (CXCL6), and IL-2 receptor gamma were all up-regulated in
      infected udders versus healthy controls. This study identified a number of
      differentially expressed genes induced by S. aureus intramammary infection and
      demonstrates the intricacy of the patterns of gene expression that influence host
      response to a complex pathogen of significant relevance to both human and
      veterinary medicine.

PMID- 20060595
TI  - A novel monoclonal antibody specific for canine CD25 (P4A10): selection and
      evaluation of canine Tregs.
AB  - A monoclonal antibody (mAb), P4A10, was made to the canine interleukin-2 receptor
      alpha chain (IL-2Ralpha; p55; Tac antigen; CD25) to facilitate studies of canine
      regulatory T-cells (Treg). By non-reduced Western blot, P4A10 bound to a 55kDa
      protein, the size of human IL-2Ralpha. In flow cytometry assays, it reacted with
      a minor population of circulating dog CD3(+)CD4(+) T-cells and the majority
      (>60%) of in vitro PMA-Ionomycin (PMA-IO)-activated canine CD3(+) T-cells. P4A10
      recognized a hematopoietic cell population enriched for FoxP3+ cells as measured
      by flow cytometry. The P4A10-selected fractions of T-cells had significantly
      increased copy numbers of CD25, FoxP3, IL-10, and TGFbeta as detected by RT-PCR
      (reverse transcriptase-PCR) compared to the negative fractions. The P4A10
      selected cells inhibited (3)H (tritiated) thymidine incorporation in a mixed
      leukocyte reaction (MLR) containing responders of the same origin. P4A10-selected
      T-cells from fresh peripheral blood mononuclear cells had less FoxP3 (p=0.07) by
      qRT-PCR (quantitative RT-PCR) and were less suppressive (p=0.01) than in vitro
      alloantigen-activated Treg. The mAb P4A10 is specific for canine CD25 and can be
      used to facilitate studies of CD25+FoxP3+ Treg in this clinically relevant large
      animal model.

PMID- 20060597
TI  - Ovis aries CR4 is involved in Mannheimia haemolytica leukotoxin-induced
      cytotoxicity.
AB  - Pneumonia caused by Mannheimia haemolytica is an important disease of domestic
      sheep (DS, Ovis aries) and cattle (BO). M. haemolytica is a normal commensal of
      the upper respiratory tract in ruminants, but during stress and viral infection
      it breaches the host innate mucosal defense and descents into lungs causing
      fibrinous pleuropneumonia. Leukotoxin (Lkt) produced by M. haemolytica is
      cytolytic to all subsets of ruminant leukocytes. Earlier, we and others have
      shown that DS and BO LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) can mediate Lkt
      induced cytolysis. It is not clear whether CR4 (CD11c/CD18), which is involved in
      chemotaxis, phagocytosis and regulates host immune response can also mediate Lkt
      induced cytolysis in ruminants. The host innate immune response to M. haemolytica
      is poorly understood and the involvement of CR4 in M. haemolytica pathogenesis is
      one of the most understudied. This problem is further compounded by the lack of
      cd11c genes from any ruminant species. Therefore, the objectives of this study
      were to clone cd11c and determine whether CR4 can serve as a receptor for Lkt. In
      this direction we cloned two alleles of cd11c gene from leukocytes isolated from
      DS blood by RT-PCR. Transfectants developed expressing functional DS CR4 were
      found to be cytotoxic to Lkt from four different isolates of M. haemolytica. This
      is the first report confirming the ability of a recombinant ovine CR4 to bind to
      M. haemolytica Lkt and mediate concentration-dependent lysis of host cells, thus,
      confirming their role in M. haemolytica pathogenesis. This is a critical step in
      understanding host innate immunity and the management of pneumonia in sheep.

PMID- 20060598
TI  - Sphingomyelinase dependent apoptosis of dendritic cells following treatment with
      amyloid peptides.
AB  - Amyloid peptides are formed during inflammation and modify the function of immune
      cells. The present study explored the effect of amyloid beta-peptide (Abeta(1
      42)) and islet amyloid polypeptide (IAPP) on bone marrow derived dendritic cells
      (DCs). DCs were treated with Abeta(1-42) or IAPP with subsequent assessment of
      ceramide formation, caspase 8 and 3 activity, DNA fragmentation and
      phosphatidylserine exposure. In addition, TNFalpha secretion was assessed in
      lypopolysaccharide (LPS)-stimulated Abeta(1-42)- or IAPP-treated DCs. Within 24h
      Abeta(1-42) and IAPP triggered ceramide formation, caspase 8 and caspase 3
      activation, DNA fragmentation and annexin V binding in DCs obtained from wild
      type mice, whereas in DCs from sphingomyelinase deficient (asm(-/-)) mice and in
      wild type DCs treated with sphingomyelinase inhibitor amitriptyline all these
      effects were strongly impaired. Moreover, ceramide formation was also reduced in
      wild type DCs in which acid sphingomyelinase (Asm) was silenced with Asm-targeted
      siRNA. Finally, Abeta(1-42) and IAPP treatment was further followed by a decline
      of TNFalpha formation in wild type DCs. In conclusion, amyloid peptides induce DC
      apoptosis presumably through activation of acid sphingomyelinase resulting in
      production of ceramide.

PMID- 20060599
TI  - KTP laser: an important tool in refractory recurrent tracheo-esophageal fistula
      in children.
AB  - Secondary tracheo-oesophageal fistula in delayed primary repair of oesophageal
      atresia is rare. This paper reports the successful use of the KTP laser in the
      treatment of this condition in a refractory case. It also recommends the use of
      direct laryngotracheobronchoscopy (DLTB) in the diagnosis. We recommend the use
      of this laser in cases of recurrent tracheo-esophageal fistula especially when
      other means have failed.

PMID- 20060601
TI  - An endocrine disrupting chemical changes courtship and parental care in the sand
      goby.
AB  - Endocrine disrupting chemicals (EDCs) are a diverse group of compounds that can
      mimic, block or modulate the synthesis of natural hormones. They are known to
      cause impairment of reproduction of aquatic organisms at very low concentrations.
      The aim of this study was to examine how exposure from 10 to 31 days to 17alpha
      ethinyl estradiol (EE2, 41 ng L(-1)) affects the courtship and parental care
      behaviour of male sand gobies (Pomatoschistus minutus). The sand goby exhibits a
      polygynous mating system, where males compete for females and provide paternal
      care. First, male courtship performance towards a stimulus female was recorded
      with video camera. Secondly, after the male had received eggs his parental care
      behaviour was video recorded. In addition to behavioural endpoints, we measured
      the expression of hepatic vitellogenin (Vtg) and zona radiata protein (Zrp) mRNA,
      as well as common somatic indices. Our study shows that exposure to EE2 affected
      male fanning behaviour during both courtship and parental care. Interestingly,
      small exposed males increased their courtship fanning to similar levels as larger
      control males. However, during parental care egg fanning was not related to male
      size, and all exposed males fanned more than control males. The EE2-exposure
      induced Vtg and Zrp mRNA expression in males and decreased hepatosomatic index
      (HSI), and increased gonadosomatic index (GSI). Females prefer males that fan
      more, which will favour the small EDC exposed males. This may lead to mating that
      favours males that are not strong enough to tend the eggs until they hatch, thus
      decreasing the reproductive success of individuals.

PMID- 20060602
TI  - Effects of brevetoxin exposure on the immune system of loggerhead sea turtles.
AB  - Blooms of the toxic dinoflagellate, Karenia brevis, occur almost annually off the
      Florida coast. These blooms, commonly called "red tides", produce a group of
      neurotoxins collectively termed brevetoxins. Many species of sealife, including
      sea turtles, are severely impacted by brevetoxin exposure. Effects of brevetoxins
      on immune cells were investigated in rescued loggerhead sea turtles, Caretta
      caretta, as well as through in vitro experiments using peripheral blood
      leukocytes (PBL) collected from captive sea turtles. In rescued animals, plasma
      brevetoxin concentrations were measured using a competitive ELISA. Plasma
      lysozyme activity was measured using a turbidity assay. Lysozyme activity
      correlated positively with plasma brevetoxin concentrations. Differential
      expression of genes affected by brevetoxin exposure was determined using two
      separate suppression subtractive hybridization experiments. In one experiment,
      genes from PBL collected from sea turtles rescued from red tide toxin exposure
      were compared to genes from PBL collected from healthy captive loggerhead sea
      turtles. In the second experiment, PBL from healthy captive loggerhead sea
      turtles were exposed to brevetoxin (500 ng PbTx-2/ml) in vitro for 18 h and
      compared to unexposed PBL. Results from the subtraction hybridization experiment
      conducted with red tide rescued sea turtle PBL indicated that genes involved in
      oxidative stress or xenobiotic metabolism were up-regulated. Using quantitative
      real-time PCR, a greater than 2-fold increase in superoxide dismutase and
      thioredoxin and greater than 10-fold increase in expression of thiopurine S
      methyltransferase were observed. Results from the in vitro subtraction
      hybridization experiment indicated that genes coding for cytochrome c oxidases
      were the major up-regulated genes. Using quantitative real-time PCR, a greater
      than 8-fold increase in expression of beta-tubulin and greater than 3-fold
      increase in expression of ubiquinol were observed. Brevetoxin exposure may have
      significant implications for immune function in loggerhead sea turtles.

PMID- 20060600
TI  - Early transformations in odor representation.
AB  - Sensory representations are repeatedly transformed by neural computations that
      determine which of their attributes can be effectively processed at each stage.
      Whereas some early computations are common across multiple sensory systems, they
      can utilize dissimilar underlying mechanisms depending on the properties of each
      modality. Recent work in the olfactory bulb has substantially clarified the
      neural algorithms underlying early odor processing. The high-dimensionality of
      odor space strictly limits the utility of topographical representations, forcing
      similarity-dependent computations such as decorrelation to employ unusual neural
      algorithms. The distinct architectures and properties of the two prominent
      computational layers in the olfactory bulb suggest that the bulb is directly
      comparable not only to the retina but also to primary visual cortex.

PMID- 20060603
TI  - Silver nanospheres are cytotoxic and genotoxic to fish cells.
AB  - Nanoparticles are being widely investigated for a range of applications due to
      their unique physical properties. For example, silver nanoparticles are used in
      commercial products for their antibacterial and antifungal properties. Some of
      these products are likely to result in silver nanoparticles reaching the aquatic
      environment. As such, nanoparticles pose a health concern for humans and aquatic
      species. We used a medaka (Oryzias latipes) cell line to investigate the
      cytotoxicity and genotoxicity of 30nm diameter silver nanospheres. Treatments of
      0.05, 0.3, 0.5, 3 and 5microg/cm(2) induced 80, 45.7, 24.3, 1 and 0.1% survival,
      respectively, in a colony forming assay. Silver nanoparticles also induced
      chromosomal aberrations and aneuploidy. Treatments of 0, 0.05, 0.1 and
      0.3microg/cm(2) induced damage in 8, 10.8, 16 and 15.8% of metaphases and 10.8,
      15.6, 24 and 24 total aberrations in 100 metaphases, respectively. These data
      show that silver nanoparticles are cytotoxic and genotoxic to fish cells.

PMID- 20060604
TI  - Effects of ivermectin-spiked cattle dung on a water-sediment system with the
      aquatic invertebrates Daphnia magna and Chironomus riparius.
AB  - A two-species test using a water-sediment test system was performed to
      investigate chronic effects of the parasiticide ivermectin on Daphnia magna and
      Chironomus riparius. To simulate exposure by direct excretion of cattle into
      surface waters, ivermectin was applied via spiked cattle dung. The parasiticide
      was applied once, at concentrations ranging from 11 to 1314 microg kg(-1) dung
      dry weight. The highest concentration corresponds to the maximum concentration in
      dung 3 days after topical application to cattle. Test vessels were stocked with
      chironomid larvae and daphnids of defined, mixed age. Replicates were sampled 10,
      24, 38 and 51 days post application. Survival, growth and emergence of
      chironomids, and abundance and biomass of daphnids were evaluated. In case of
      extinction of the D. magna population in all replicates of a concentration level,
      daphnids were re-introduced into the remaining vessels of this concentration to
      simulate immigration. In addition, a second batch of chironomid larvae was
      introduced into the vessels on day 27 post application. At 1314 microg ivermectin
      kg(-1) dung dry weight, survival, larval growth and emergence of the initially
      stocked chironomids were strongly affected. A significant effect on emergence was
      also observed for the second batch of chironomids. The two highest test
      concentrations led to 100% mortality of the initially stocked daphnids. At 1314
      microg kg(-1) dung dry weight, no daphnids survived following re-introduction on
      days 11, 28 and 42. At 263 microg kg(-1) dung dry weight, the daphnids that were
      re-introduced on day 11 survived and reproduced, but abundance and biomass were
      reduced. The results of the present study indicate that following single
      application, toxic ivermectin concentrations persisted for an extended period.
      Possible effects on aquatic invertebrates, which may be caused by direct
      excretion of ivermectin-containing dung into surface water, deserve further
      attention.

PMID- 20060605
TI  - Acetylbritannilactone induces G1 arrest and apoptosis in vascular smooth muscle
      cells.
AB  - BACKGROUND: The present study was designed to determine the effects of
      Acetylbritannilactone (ABL), a naturally occurring Inula britannica L., on
      vascular smooth muscle cell (VSMC) proliferation and apoptosis. METHODS: In vitro
      experiments were performed to evaluate the effects of ABL on the VSMC cycle and
      apoptosis stimulated by chemoattractant. In addition, to examine the effects of
      ABL in vivo, balloon injury to rat carotid arteries was performed. RESULTS: ABL
      treatment inhibited platelet-derived growth factor (PDGF) induced DNA synthesis
      and proliferation in cultured VSMC. Such growth-inhibitory effects of ABL were
      associated with G1 phase arrest, which were correlated with reduction of cyclins
      D1, A, and E expression and cyclin-dependent kinase (CDK) 2, CDK4, and CDK6
      proteins, increased the CDK inhibitory protein p21cip1 expression, and enhanced
      the binding of p21cip1 to CDKs. In addition, ABL also induced apoptosis in
      proliferative VSMCs, as evidenced by the induction of a higher ratio of Bax/Bcl
      2, activation of caspase-9, caspase-3, and the cleavage of endogenous substrate
      Poly (ADP-ribose) polymerase. However, pretreatment with pan-caspases inhibitor
      (z-VAD-fmk) only partially reversed ABL-induced apoptosis, suggesting the
      involvement of both caspase-dependent and caspase-independent pathways in these
      processes. Furthermore, the effects of ABL on VSMCs were associated with the
      downregulation of extracellular signal-regulated kinase (ERK) 1/2 signaling
      pathways. In vivo, ABL (26 mg/kg/day) significantly suppressed injury-induced
      ERK1/2 phosphorylation, and increased VSMC apoptosis 14 days after balloon
      injury. CONCLUSIONS: Our findings demonstrated that ABL was capable of
      suppressing the abnormal VSMC proliferation, accompanied by the induction of
      apoptosis in vivo and in vitro. It suggested that ABL could be considered a
      pharmacological candidate for the prevention of restenosis after balloon
      angioplasty.

PMID- 20060606
TI  - Illustration of the heart and blood vessels in medieval times.
AB  - Throughout history, illustrations had played a key role in the promotion and
      evolution of medicine by providing a medium for transmission of scientific
      observations. Due to religious prohibitions, color drawings of the human body did
      not appear in medieval Persia and during the Islamic Golden Age. This tradition,
      however, has been overlooked with the publication of the first color atlas and
      text of human anatomy, Tashrihi Mansuri (Mansur's Anatomy), by Mansur ibn Ilyas
      in the fourteenth century AD. Written in Persian and containing several vivid
      illustrations of the human body, this book gained widespread attention by both
      scholars and lay persons. In this article, a brief history of Mansur's Anatomy
      and an English translation of selected sections from this book regarding the
      heart and blood vessels are presented.

PMID- 20060607
TI  - Postoperative echocardiographic followup for patients with mitral valve prolapse
      is essential after mitral valve repair.

PMID- 20060608
TI  - Prehension synergy: effects of static constraints on multi-finger prehension.
AB  - Previous studies have shown that the interactions of human hand digits are
      influenced by internal constraints, i.e., biomechanical and central constraints.
      However, little is currently known about the influence of externally imposed
      mechanical constraints on multi-finger behavior. This study investigates maximal
      digit force production during fixed object and free object prehension in statics.
      The results from the fixed object prehension indicated that the closer the non
      task finger was positioned to the task finger, the greater the force produced by
      the non-task finger, which supports the proximity hypothesis. Conversely, the non
      task fingers with longer moment arms showed greater force production during free
      object prehension, which supports the mechanical advantage hypothesis. During the
      free object prehension, equal and opposite torques were produced by the digit
      normal forces and tangential forces, while this phenomenon was not observed in
      the fixed object prehension. The results also showed that the thumb normal force
      had a positive linear relationship with task-finger normal forces during fixed
      object prehension while the thumb normal force remained constant during free
      object prehension tasks. We concluded that the CNS employed different strategies
      when different sets of internal and external constraints are provided during
      multi-digit prehension tasks.

PMID- 20060609
TI  - An investigation of stride interval stationarity in a paediatric population.
AB  - Fluctuations in the stride interval of human gait have been found to exhibit
      statistical persistence over hundreds of strides, the extent of which changes
      with age, pathology, and speed-constrained walking. Thus, recent investigations
      have focused on quantifying this scaling behavior in order to gain insight into
      locomotor control. While the ability of a given analysis technique to provide an
      accurate scaling estimate depends largely on the stationary properties of the
      given series, direct investigation of stride interval stationarity has been
      largely overlooked. In the present study we test the stride interval time series
      obtained from able-bodied children for weak stationarity. Specifically, we
      analyze signals obtained during three distinct modes of self-paced locomotion:
      (i) overground walking, (ii) unsupported (hands-free) treadmill walking, and
      (iii) handrail-supported treadmill walking. Using the reverse arrangements test,
      we identify non-stationary signals in all three walking conditions and find the
      major known cause to be due to time-varying first and second moments. We further
      discuss our findings in terms of locomotor control and the differences between
      the locomotor modalities investigated. Overall, our results advocate against
      scaling analysis techniques that assume stationarity.

PMID- 20060611
TI  - Inhibitory effect of boron against Botrytis cinerea on table grapes and its
      possible mechanisms of action.
AB  - Boron, an essential plant micronutrient, was effective in the form of potassium
      tetraborate for control of postharvest gray mold caused by Botrytis cinerea on
      table grapes stored at room temperature or at 0 degrees C. The inhibition of
      fruit decay was closely correlated with boron concentrations and partially
      influenced by pH value of the solution. Boron strongly inhibited spore
      germination, germ tube elongation, and mycelial spread of B. cinerea in the
      culture medium. Application of boron at 1% caused the appearance of abnormal
      spores (disrupted) in some cases. By using propidium iodide fluorescent staining,
      loss of membrane integrity in B. cinerea was observed after boron treatment.
      Furthermore, boron led to the leakage of cellular constituents (soluble proteins
      and carbohydrates) from hyphae of B. cinerea. These data suggest that the
      mechanisms by which boron decreased gray mold decay of table grapes may be
      directly related to the disruption effect of boron on cell membrane of the fungal
      pathogen that resulted in the breakdown of the cell membrane and loss of
      cytoplasmic materials from the hyphae.

PMID- 20060610
TI  - Stages in learning motor synergies: a view based on the equilibrium-point
      hypothesis.
AB  - This review describes a novel view on stages in motor learning based on recent
      developments of the notion of synergies, the uncontrolled manifold hypothesis,
      and the equilibrium-point hypothesis (referent configuration) that allow to merge
      these notions into a single scheme of motor control. The principle of abundance
      and the principle of minimal final action form the foundation for analyses of
      natural motor actions performed by redundant sets of elements. Two main stages of
      motor learning are introduced corresponding to (1) discovery and strengthening of
      motor synergies stabilizing salient performance variable(s) and (2) their
      weakening when other aspects of motor performance are optimized. The first stage
      may be viewed as consisting of two steps, the elaboration of an adequate referent
      configuration trajectory and the elaboration of multi-joint (multi-muscle)
      synergies stabilizing the referent configuration trajectory. Both steps are
      expected to lead to more variance in the space of elemental variables that is
      compatible with a desired time profile of the salient performance variable ("good
      variability"). Adjusting control to other aspects of performance during the
      second stage (for example, esthetics, energy expenditure, time, fatigue, etc.)
      may lead to a drop in the "good variability". Experimental support for the
      suggested scheme is reviewed.

PMID- 20060612
TI  - Characterization of Streptococcus thermophilus lytic bacteriophages from
      mozzarella cheese plants.
AB  - Phage infection still represents the main cause of fermentation failure during
      the mozzarella cheese manufacturing, where Streptococcus thermophilus is widely
      employed as starter culture. Thereby, the success of commercial lactic starter
      cultures is closely related to the use of strains with low susceptibility to
      phage attack. The characterization of lytic S. thermophilus bacteriophages is an
      important step for the selection and use of starter cultures. The aim of this
      study was to characterize 26 bacteriophages isolated from mozzarella cheese
      plants in terms of their host range, DNA restriction profile, DNA packaging
      mechanism, and the variable region VR2 of the antireceptor gene. The DNA
      restriction analysis was carried out by using the restriction enzymes EcoRV,
      PstI, and HindIII. The bacteriophages were distinguished into two main groups of
      S. thermophilus phages (cos- and pac-type) using a multiplex PCR method based on
      the amplification of conserved regions in the genes coding for the major
      structural proteins. All the phages belonged to the cos-type group except one,
      phage 1042, which gave a PCR fragment distinctive of pac-type group. Furthermore,
      DNA sequencing of the variable region VR2 of the antireceptor gene allowed to
      classify the phages and examine the correlation between typing profile and host
      range. Finally, bacterial strains used in this study were investigated for the
      presence of temperate phages by induction with mitomycin C and only S.
      thermophilus CHCC2070 was shown to be lysogenic.

PMID- 20060613
TI  - Norwegian priority guidelines: estimating the distributional implications across
      age, gender and SES.
AB  - OBJECTIVE: Targeting hospital treatment at patients with high priority would seem
      to be a natural policy response to the growing gap between what can be done and
      what can be financed in the specialist health care sector. The paper examines the
      distributional consequences of this policy. METHOD: 450000 elective patients are
      allocated to priority groups on the basis of medical guidelines developed by one
      of the regional health authorities in Norway. Probit models are estimated
      explaining priority status as a function of age, gender and socioeconomic status.
      RESULTS: Women and older people are overrepresented among patients with low
      priority. Conditional on age, women with low priority have lower income and less
      education than women with high priority. Among men below 50 years, patients with
      low priority have less education than patients with high priority. CONCLUSION:
      Targeting hospital treatment at patients with high priority, though sensible from
      a pure medical perspective, may have undesirable distributional consequences.

PMID- 20060614
TI  - Toward fully automated processing of dynamic susceptibility contrast perfusion
      MRI for acute ischemic cerebral stroke.
AB  - We developed fully automated software for dynamic susceptibility contrast (DSC)
      MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical
      hemodynamic information for acute stroke treatment decisions. Brain MR PWI was
      performed in 80 consecutive patients with acute nonlacunar ischemic stroke within
      24h after onset of symptom from January 2008 to August 2009. These studies were
      automatically processed to generate hemodynamic parameters that included cerebral
      blood flow and cerebral blood volume, and the mean transit time (MTT). To develop
      reliable software for PWI analysis, we used computationally robust algorithms
      including the piecewise continuous regression method to determine bolus arrival
      time (BAT), log-linear curve fitting, arrival time independent deconvolution
      method and sophisticated motion correction methods. An optimal arterial input
      function (AIF) search algorithm using a new artery-likelihood metric was also
      developed. Anatomical locations of the automatically determined AIF were reviewed
      and validated. The automatically computed BAT values were statistically compared
      with estimated BAT by a single observer. In addition, gamma-variate curve-fitting
      errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two
      observes independently assessed the quality and area of hypoperfusion mismatched
      with restricted diffusion area from motion corrected MTT maps and compared that
      with time-to-peak (TTP) maps using the standard approach. The AIF was identified
      within an arterial branch and enhanced areas of perfusion deficit were visualized
      in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.)
      without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a
      standard personal computer. The MTT map produced with our software adequately
      estimated brain areas with perfusion deficit and was significantly less affected
      by random noise of the PWI when compared with the TTP map. Results of image
      quality assessment by two observers revealed that the MTT maps exhibited superior
      quality over the TTP maps (88% good rating of MTT as compared to 68% of TTP). Our
      software allowed fully automated deconvolution analysis of DSC PWI using proven
      efficient algorithms that can be applied to acute stroke treatment decisions. Our
      streamlined method also offers promise for further development of automated
      quantitative analysis of the ischemic penumbra.

PMID- 20060615
TI  - In situ measurements of volatile aromatic hydrocarbon biodegradation rates in
      groundwater.
AB  - Benzene and alkylbenzene biodegradation rates and patterns were measured using an
      in situ microcosm in a crude-oil contaminated aquifer near Bemidji, Minnesota.
      Benzene-D6, toluene, ethylbenzene, o-, m- and p-xylenes and four pairs of C(3)-
      and C(4)-benzenes were added to an in situ microcosm and studied over a 3-year
      period. The microcosm allowed for a mass-balance approach and quantification of
      hydrocarbon biodegradation rates within a well-defined iron-reducing zone of the
      anoxic plume. Among the BTEX compounds, the apparent order of persistence is
      ethylbenzene > benzene > m,p-xylenes > o-xylene >or= toluene. Threshold
      concentrations were observed for several compounds in the in situ microcosm,
      below which degradation was not observed, even after hundreds of days. In
      addition, long lag times were observed before the onset of degradation of benzene
      or ethylbenzene. The isomer-specific degradation patterns were compared to
      observations from a multi-year study conducted using data collected from
      monitoring wells along a flowpath in the contaminant plume. The data were fit
      with both first-order and Michaelis-Menten models. First-order kinetics provided
      a good fit for hydrocarbons with starting concentrations below 1mg/L and
      Michaelis-Menten kinetics were a better fit when starting concentrations were
      above 1mg/L, as was the case for benzene. The biodegradation rate data from this
      study were also compared to rates from other investigations reported in the
      literature.

PMID- 20060616
TI  - Abscisic acid signals reorientation of polyamine metabolism to orchestrate stress
      responses via the polyamine exodus pathway in grapevine.
AB  - Polyamines (PAs) have been suggested to be implicated in plant responses to
      abiotic and biotic stress. Grapevine is a model perennial plant species whose
      cultivars respond differently to osmotic stress. In this study, we used two
      cultivars, one sensitive (S) and one tolerant (T) to drought. In adult vines
      subjected to drought under greenhouse conditions, total PAs were significantly
      lower in the control T- and higher in the control S-genotype and significantly
      increased or decreased, respectively, post-treatment. Soluble Put and Spd
      exhibited the greatest increase on d 8 post-treatment in the T- but not in the S
      genotype, which accumulated soluble Spm. Abscisic acid (ABA) was differentially
      accumulated in T- and S-genotypes under drought conditions, and activated the PA
      biosynthetic pathway, which in turn was correlated with the differential
      increases in PA titers. In parallel, polyamine oxidases (PAOs) increased
      primarily in the S-genotype. ABA at least partially induced PA accumulation and
      exodus into the apoplast, where they were oxidized by the apoplastic amine
      oxidases (AOs), producing H2O2, which signaled secondary stress responses. The
      results here show that the ABA signaling pathway integrates PAs and AOs to
      regulate the generation of H2O2, which signals further stress responses or the
      PCD syndrome.

PMID- 20060617
TI  - [Iridocorneal-endothelial syndrome: description of idiopathic atrophy of the
      iris].

PMID- 20060618
TI  - Do surface and cleaning chemistries interfere with ATP measurement systems for
      monitoring patient room hygiene?

PMID- 20060619
TI  - Use of octenidine dihydrochloride in meticillin-resistant Staphylococcus aureus
      decolonisation regimens: a literature review.
AB  - Decolonisation of patients colonised with meticillin-resistant Staphylococcus
      aureus (MRSA) is one of the recommended methods for controlling MRSA in hospitals
      but there is a limited choice of agents that can be used. Octenidine
      dihydrochloride is a relatively new antiseptic that has been used for MRSA
      decolonisation in some countries. On reviewing available literature on its use
      for MRSA decolonisation, only four observational studies were found. All of these
      were small studies, which differed in study design. MRSA decolonisation rates of
      6-75% have been reported. Patients with wound colonisation were included in these
      studies but it was not clear if the hair was treated in two of these. Octenidine
      appears to be as effective as chlorhexidine for MRSA decolonisation with fewer
      adverse effects, but large randomised trials incorporating octenidine as a skin
      disinfectant for MRSA decolonisation need to be undertaken to confirm its
      usefulness in clinical settings.

PMID- 20060620
TI  - Outbreak of nosocomial diarrhoea caused by enterotoxigenic Escherichia coli in a
      geriatric ward.

PMID- 20060621
TI  - Mutational screening and zebrafish functional analysis of GIGYF2 as a Parkinson
      disease gene.
AB  - The Grb10-Interacting GYF Protein-2 (GIGYF2) gene has been proposed as the
      Parkinson-disease (PD) gene underlying the PARK11 locus. However, association of
      GIGYF2 with PD has been challenged and a functional validation of GIGYF2
      mutations is lacking. In this frame, we performed a mutational screening of
      GIGYF2 in an Italian PD cohort. Exons containing known mutations were analyzed in
      552 cases and 552 controls. Thereafter, a subset of 184 familial PD cases and
      controls were subjected to a full coding-exon screening. These analyses
      identified 8 missense variations in 9 individuals (4 cases, 5 controls).
      Furthermore, we developed a zebrafish model of gigyf2 deficiency. Abrogation of
      gigyf2 function in zebrafish embryos did not lead to a drastic cell loss in
      diencephalic dopaminergic (DA) neuron clusters, suggesting that gigyf2 is not
      required for DA neuron differentiation. Notably, gigyf2 functional abrogation did
      not increase diencephalic DA neurons susceptibility to the PD-inducing drug MPP+.
      These data, together with those recently reported by other groups, suggest that
      GIGYF2 is unlikely to be the PARK11 gene.

PMID- 20060622
TI  - Design, synthesis and evaluation of analogs of initiation factor 4E (eIF4E) cap
      binding antagonist Bn7-GMP.
AB  - Aberrant regulation of cap-dependent translation has been frequently observed in
      the development of cancer. Association of the cap-binding protein eIF4E with N(7)
      methylated guanosine capped mRNA is the rate limiting step governing translation
      initiation; and therefore represents an attractive process for cancer drug
      discovery. Previously, replacement of the 7-Me group of the Me(7)-guanosine
      monophosphate with a benzyl group has been found to increase binding affinity to
      eIF4E. Recent X-ray crystallographic studies have revealed that the cap-binding
      pocket undergoes a unique structural change in order to accommodate the benzyl
      group. To explore the structure-activity relationships governing the affinity of
      N(7)-benzylated guanosine monophosphate (Bn(7)-GMP) for eIF4E, we virtually
      screened a library of 80 Bn(7)-GMP analogs utilizing CombiGlide as implemented in
      Schrodinger. A subset library of substituted Bn(7)-GMP analogs was synthesized
      and their dissociation constants (K(d)) were determined. Due to the poor
      correlation between docking/scoring results and experimental binding affinities,
      three-dimensional quantitative structure-activity relationship (3D-QSAR)
      calculations were performed. Two highly predictive and self-consistent CoMFA
      (comparative molecular field analysis) and CoMSIA (comparative molecular
      similarity indices analysis) models were derived and optimized. These models may
      be useful for the future design of eIF4E cap-binding antagonists.

PMID- 20060623
TI  - Synthesis and pharmacological evaluation of new 5-(cyclo)alkyl-5-phenyl- and 5
      spiroimidazolidine-2,4-dione derivatives. Novel 5-HT1A receptor agonist with
      potential antidepressant and anxiolytic activity.
AB  - The synthesis of 5-(cyclo)alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione
      derivatives with an arylpiperazinylpropyl moiety (12-23) and their in vitro and
      in vivo pharmacological properties and molecular characteristics were described.
      The investigated compounds exhibited high affinity for 5-HT(1A) (13-22) and 5
      HT(2A) (18, 20, 21, 23) receptors and diversified pharmacological profile.
      Compounds 17, 20 and 22 showed antagonistic, partial agonistic and agonistic
      activity, respectively, toward 5-HT(1A) receptor and they were investigated as
      potential antidepressants and/or anxiolytics. The most interesting compound 22 (1
      [3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl]-3',4'-dihydro-2'H
      spiro[imidazolidine-4,1'-naphthalene]-2,5-dione), a pre- and postsynaptic 5
      HT(1A) receptor agonist produced an antidepressant-like effect, which was more
      pronounced than that of imipramine in the forced swim test in mice, without
      affecting locomotor activity. Moreover, compound 22 produced a weak anxiolytic
      like effect in the four-plate test in mice. Molecular docking studies of compound
      22 to the homology model of the 5-HT(1A) receptor showed that a 3',4'-dihydro-2'H
      spiro[imidazolidine-4,1'-naphthalene]-2,5-dione moiety played an important role
      in stabilizing the ligand-receptor complex.

PMID- 20060624
TI  - Synthesis and antibacterial activity of 5-ylidenethiazolidin-4-ones and 5
      benzylidene-4,6-pyrimidinediones.
AB  - 5-benzylidenethiazolidin-4-ones and 5-benzylidenepyrimidine-4,6-diones (compounds
      1-9), carrying 2,3,4-trifluoro or 3,4,5-trimethoxy groups on the benzylidene
      moiety, and rhodanine derivatives 10 and 11 were synthesized and assayed in vitro
      for their antimicrobial activity against four standard bacterial strains
      (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Escherichia
      coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). Compounds 1-3 and 9 that
      were active against S. aureus, were also tested against methicillin-resistant S.
      aureus (MRSA) ATCC 43300, Streptococcus pneumoniae ATCC 49619 and Streptococcus
      pyogenes ATCC 19615. (Z)-5-(2,3,4-Trifluorobenzylidene)rhodanine (1) inhibited
      the growth of S. aureus at 0.5 microg/mL and MRSA at 32 microg/mL. Stronger
      antimicrobial activity against S. aureus was observed for compounds bearing the
      rhodanine ring than those containing other heterocyclic moieties. Neither of the
      compounds 1-11 inhibited the growth of Gram-negative bacteria E. coli or P.
      aeruginosa.

PMID- 20060625
TI  - MIA-QSAR coupled to principal component analysis-adaptive neuro-fuzzy inference
      systems (PCA-ANFIS) for the modeling of the anti-HIV reverse transcriptase
      activities of TIBO derivatives.
AB  - The activities of a series of HIV reverse transcriptase inhibitor TIBO
      derivatives were recently modeled by using genetic function approximation (GFA)
      and artificial neural networks (ANN) on topological, structural, electronic,
      spatial and physicochemical descriptors. The prediction results were found to be
      superior to those previously established. In the present work, the multivariate
      image analysis applied to quantitative structure-activity relationship (MIA-QSAR)
      method coupled to principal component analysis-adaptive neuro-fuzzy inference
      systems (PCA-ANFIS), which accounts for non-linearities, was applied on the same
      set of compounds previously reported. Additionally, partial least squares (PLS)
      and multilinear partial least squares (N-PLS) regressions were used for
      comparison with the MIA-QSAR/PCA-ANFIS model. The ANFIS procedure was capable of
      accurately correlating the inputs (PCA scores) with the bioactivities. The
      predictive performance of the MIA-QSAR/PCA-ANFIS model was significantly better
      than the MIA-QSAR/PLS and N-PLS models, as well as than the reported models based
      on CoMFA, CoMSIA, OCWLGI and classical descriptors, suggesting that the present
      methodology may be useful to solve other QSAR problems, specially those involving
      non-linearities.

PMID- 20060626
TI  - Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document
      elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting
      diseases" and "nutrition in geriatrics".
AB  - Chronic diseases as well as aging are frequently associated with deterioration of
      nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired
      quality of life and increased risk for morbidity and mortality. Although simple
      and effective tools for the accurate screening, diagnosis and treatment of
      malnutrition have been developed during the recent years, its prevalence still
      remains disappointingly high and its impact on morbidity, mortality and quality
      of life clinically significant. Based on these premises, the Special Interest
      Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within
      ESPEN with the aim of developing and spreading the knowledge on the basic and
      clinical aspects of cachexia and anorexia as well as of increasing the awareness
      of cachexia among health professionals and care givers. The definition, the
      assessment and the staging of cachexia, were identified as a priority by the SIG.
      This consensus paper reports the definition of cachexia, pre-cachexia and
      sarcopenia as well as the criteria for the differentiation between cachexia and
      other conditions associated with sarcopenia, which have been developed in
      cooperation with the ESPEN SIG on nutrition in geriatrics.

PMID- 20060627
TI  - Biomechanical comparison of hallux valgus correction using the proximal chevron
      osteotomy fixed with a medial locking plate and the Ludloff osteotomy fixed with
      two screws.
AB  - BACKGROUND: For moderate-to-severe hallux valgus deformities with a 1-2
      intermetatarsal angle in excess of 15 degrees , a proximal first metatarsal
      osteotomy is indicated. The ideal osteotomy has yet to be defined, but should
      inherently limit the incidence of dorsal malunion and allow for early ambulation.
      The present study evaluates the mechanical integrity of two popular first
      metatarsal osteotomies. METHODS: Ten matched pairs of fresh-frozen cadaveric
      first metatarsals were harvested. In one metatarsal from each pair, a Ludloff
      osteotomy was created and fixed with two cannulated 3.5mm screws. In the
      contralateral first metatarsal, a proximal chevron osteotomy was performed and
      subsequently fixed with a medially applied locking plate. All specimens were
      mounted within an Instron 1321 servohydraulic materials testing machine and
      subjected to a plantar-to-dorsal cantilever bending protocol for 1000 cycles.
      FINDINGS: Two of ten Ludloff osteotomies failed prior to completion of 1000
      loading cycles by fracture at the distal screw site, whereas six of ten proximal
      chevrons failed prior to the 1000th cycle. The mode of failure in this group was
      by cut-out of the plantar-proximal screw. The bending stiffness of the Ludloff
      osteotomy exceeded that of the proximal chevron at all measurement points between
      the 1st and 200th load cycles (P<0.05). After 200 cycles, an inadequate number of
      plate constructs survived to allow statistical comparison. INTERPRETATION: The
      results of the present study indicate that the proximal chevron osteotomy fixed
      with a medially based locking plate exhibits mechanical properties inferior to
      those of the Ludloff osteotomy under the tested conditions.

PMID- 20060628
TI  - Stability and variability of knee kinematics during gait in knee osteoarthritis
      before and after replacement surgery.
AB  - BACKGROUND: Patients with knee osteoarthritis often feel unstable, suffering from
      buckling (giving way) or even falling. This study aimed at characterising such
      instability, and following it over time. METHODS: We investigated treadmill
      walking in knee osteoarthritis, focusing on angular velocity of sagittal plane
      knee movements. Knee osteoarthritis patients were followed 1 year after
      replacement surgery, and were compared to healthy peers. Subjects walked at
      increasing speeds, and maximum speed was registered. To quantify stability, we
      calculated short-term (lambda(S)) and long-term (lambda(L)) Lyapunov exponents
      (the exponential rate of divergence, in state space, of trajectories originating
      from nearest neighbours), as well as the variability of knee movements, the
      latter just after heel contact. At each measurement session, patients reported
      how often they had fallen in the preceding period. FINDINGS: Patients had lower
      maximum walking speed than controls, and walked with reduced variability, post
      operatively even more so. Variability was positively related to number of falls.
      Pre-operatively, patients had higher lambda(S) at the unaffected side, which post
      operatively normalized. INTERPRETATION: Slow walking may serve being more
      cautions. Reducing variability of sagittal knee kinematics appears to reduce fall
      risk, perhaps involving paying more attention and/or using cocontraction. The pre
      operatively higher unaffected side lambda(S) could result from attempts to reduce
      the kinematic demands on the affected leg, "letting go" the unaffected leg. One
      year after the operation, this problem with unaffected lambda(S) had disappeared,
      suggesting recovery. Further study should include short-term and long-term
      stability, as well as a quantitative measure of perceived instability.

PMID- 20060629
TI  - Dissipation and metabolism of (14)C-spiroxamine in soil under laboratory
      condition.
AB  - Spiroxamine [SPX] belongs to a spiroketalamine group of substances. The
      biodegradation of [1,3-dioxolane-4-(14)C]-SPX has been examined in 2 soils of
      different physicochemical properties. The total recovery of radioactivity from
      soils was 98.6-103.5% of that applied. The total amount of extractable
      radioactivity declined with a simultaneous increase in non-extractable
      radioactivity. Volatile organics were detected at lower levels; however,
      mineralization played a marked effect on the route of SPX dissipation. The half
      life ranges between 37 and 44 d. SPX does not undergo any enantioselective
      degradation. 4 metabolites: despropyl-SPX, desethyl-SPX, SPX N-oxide and SPX acid
      were identified, applying mass spectrometric technique. Sorption-desorption data
      fitted well with a Freundlich model in log form (r(2), 0.99). K(Dsorp) ranged
      between 44 and 230, suggesting SPX ought to be considered as a substance with low
      leaching potential [groundwater ubiquity score (GUS), <1.8]. Furthermore, an
      overall low desorption of 1-11% indicates firm retention of SPX by the soils.

PMID- 20060630
TI  - Effect of short-term high-dose creatine supplementation on measured GFR in a
      young man with a single kidney.
AB  - It currently is unknown whether creatine supplementation is safe for people with
      or at risk of kidney disease. We report on the short-term effects of creatine
      supplementation on kidney function in a young man with a single kidney and mildly
      decreased glomerular filtration rate (GFR). A 20-year-old man who had undergone
      unilateral nephrectomy and presented with mildly decreased GFR without kidney
      damage underwent a trial with 35 days of creatine supplementation (20 g/d for 5
      days followed by 5 g/d for the next 30 days) and had his kidney function
      monitored. After the intervention, (51)Cr-EDTA clearance (pre, 81.6 mL/min/1.73
      m(2); post, 82.0 mL/min/1.73 m(2)), proteinuria (protein excretion: pre, 130
      mg/d; post, 120 mg/d), and electrolyte levels were unchanged. Albuminuria, serum
      urea level, and estimated creatinine clearance were decreased (pre, 4.6 mg/d;
      post, 2.9 mg/d; pre, 37 mg/d; post, 28 mg/dL; and pre, 88 mL/min/1.73 m(2); post,
      71 mL/min/1.73 m(2), respectively), whereas serum creatinine level was slightly
      increased (pre, 1.03 mg/dL; post, 1.27 mg/dL), falsely suggesting kidney function
      impairment. This prospective report suggests that short-term creatine
      supplementation may not affect kidney function in an individual with a single
      kidney, mild decreased GFR, and ingesting a high-protein diet (ie, 2.8 g/kg/d).
      This finding has great relevance considering that creatine-induced kidney disease
      has been a growing concern, even for healthy people.

PMID- 20060631
TI  - Subcapsular fluid collection: an unusual manifestation of nephrotic syndrome.

PMID- 20060632
TI  - The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative
      (KDOQI) Grant Initiative: moving clinical practice forward.

PMID- 20060633
TI  - Health inequalities between lone and couple mothers and policy under different
      welfare regimes - the example of Italy, Sweden and Britain.
AB  - This study examines the welfare state arrangements and social policy, living
      conditions and health among lone and couple mothers in three contrasting policy
      environments: Italy, Sweden and Britain. These countries fall into distinctive
      family policy categories. Data were drawn from representative national household
      interview surveys. The findings highlight both similarities and differences. Lone
      mothers had significantly worse health than couple mothers in all three
      countries, were more likely to suffer material disadvantage and were much more
      likely to be smokers. They could be considered a disadvantaged group in
      particular need in all three countries, irrespective of the policy regime. It is
      the differences between countries, however, in the experiences of lone and couple
      mothers that indicate that the prevailing policy regime really does matter. There
      were telling differences in the prevalence of lone motherhood, their composition,
      rates of joblessness, poverty and health status of lone mothers in relation to
      couple mothers in each country. These may be traced back to the main policy
      regimes of each country, but also partly reflect culture and traditions. The
      study illustrates an emerging approach to investigating the health inequalities
      impact of complex social policy contexts. The experiences of lone mothers as a
      group may serve as a 'litmus' test of how each family policy system is operating
      and offer an early warning of adverse impacts when policies change.

PMID- 20060634
TI  - Job insecurity and health: a study of 16 European countries.
AB  - Although the number of insecure jobs has increased considerably over the recent
      decades, relatively little is known about the health consequences of job
      insecurity, their international pattern, and factors that may modify them. In
      this paper, we investigated the association between job insecurity and self-rated
      health, and whether the relationship differs by country or individual-level
      characteristics. Cross-sectional data from 3 population-based studies on job
      insecurity, self-rated health, demographic, socioeconomic, work-related and
      behavioural factors and lifetime chronic diseases in 23,245 working subjects aged
      45-70 years from 16 European countries were analysed using logistic regression
      and meta-analysis. In fully adjusted models, job insecurity was significantly
      associated with an increased risk of poor health in the Czech Republic, Denmark,
      Germany, Greece, Hungary, Israel, the Netherlands, Poland and Russia, with odds
      ratios ranging between 1.3 and 2.0. Similar, but not significant, associations
      were observed in Austria, France, Italy, Spain and Switzerland. We found no
      effect of job insecurity in Belgium and Sweden. In the pooled data, the odds
      ratio of poor health by job insecurity was 1.39. The association between job
      insecurity and health did not differ significantly by age, sex, education, and
      marital status. Persons with insecure jobs were at an increased risk of poor
      health in most of the countries included in the analysis. Given these results and
      trends towards increasing frequency of insecure jobs, attention needs to be paid
      to the public health consequences of job insecurity.

PMID- 20060635
TI  - The relationship of physical activity and overweight to objectively measured
      green space accessibility and use.
AB  - This study examines the association between objectively measured access to green
      space, frequency of green space use, physical activity, and the probability of
      being overweight or obese in the city of Bristol, England. Data from the 2005
      Bristol Quality of Life in your Neighbourhood survey for 6821 adults were
      combined with a comprehensive GIS database of neighbourhood and green space
      characteristics. A range of green space accessibility measures were computed.
      Associations between accessibility and the odds of respondents achieving a
      recommended 30min or more of moderate activity five times a week, or being
      overweight or obese, were examined using logistic regression. Results showed that
      the reported frequency of green space use declined with increasing distance. The
      study also found that respondents living closest to the type of green space
      classified as a Formal park were more likely to achieve the physical activity
      recommendation and less likely to be overweight or obese. The association with
      physical activity, but not with overweight or obesity, remained after adjustment
      for respondent characteristics, area deprivation, and a range of characteristics
      of the neighbourhood environment. The findings suggest that the provision of good
      access to green spaces in urban areas may help promote population physical
      activity.

PMID- 20060636
TI  - Retroperitoneal tuberculosis in a patient with uterine papillary serous
      carcinoma.

PMID- 20060637
TI  - Real-time observation of model membrane dynamics induced by Alzheimer's amyloid
      beta.
AB  - Amyloid beta (Abeta) has been strongly implicated in inducing neurotoxicity in
      the pathology of Alzheimer's disease (AD). However, the underlying mechanisms
      remain unknown. In this study, we examined, in real-time, the spatio-temporal
      changes in individual model membranes induced by the presence of different Abeta
      40 molecular assemblies (species). We used cell-sized lipid vesicles to enable
      the direct observation of these changes. We found three significantly different
      membrane-transformation pathways. We characterized the biophysical mechanisms
      behind these transformations in terms of the change in inner vesicle volume and
      surface area. Oligomeric Abeta exhibited the highest tendency to cause membrane
      fluctuation and transformations. Interestingly, mature fibrils, which are often
      considered inert species, also induced profound membrane changes. Furthermore, we
      imaged the localization of pre-fibrillar species on membranes. The real-time
      observation of these morphological transformations, which can be missed in a
      discretised analysis, may help to unlock the mechanisms of AD's Abeta-induced
      neuro-degeneration.

PMID- 20060638
TI  - Adsorption studies of hazardous malachite green onto treated ginger waste.
AB  - Adsorption of malachite green (MG) from aqueous solution onto treated ginger
      waste (TGW) was investigated by batch and column methods. The effect of various
      factors such as initial dye concentration, contact time, pH and temperature were
      studied. The maximum adsorption of MG was observed at pH 9. Langmuir and
      Freundlich isotherms were employed to describe the MG adsorption equilibrium. The
      monolayer adsorption capacities were found to be 84.03, 163.9 and 188.6 mg/g at
      30, 40 and 50 degrees C, respectively. The values of thermodynamic parameters
      like DeltaG degrees , DeltaH degrees and DeltaS degrees indicated that adsorption
      was spontaneous and endothermic in nature. The pseudo second order kinetic model
      fitted well in correlation to the experimental results. Rechienberg's equation
      was employed to determine the mechanism of adsorption. The results indicated that
      film diffusion was a major mode of adsorption. The breakthrough capacities were
      also investigated.

PMID- 20060639
TI  - Improved prediction of heats of sublimation of energetic compounds using their
      molecular structure.
AB  - A simple method is used to predict heats of sublimation of energetic compounds,
      which include nitroaromatics, nitramines, nitroaliphatics and nitrate esters.
      Molecular weight, some specific functional groups and structural parameters are
      fundamental factors in the new model. The root-mean-square deviation (rms) from
      experiment has been calculated for the predicted results of 92 different
      compounds. The calculated results for 15 compounds are also compared with
      complicated quantum mechanical computations, where computed outputs were
      available. The rms deviations of new correlation and reported quantum mechanical
      method are 9.9 and 13.8 kJ/mol, respectively. The present method improves earlier
      efforts of previous models through its application for important classes of
      energetic compounds, which contain the energetic bonds Ar-NO(2), N-NO(2), C-NO(2)
      and C-O-NO(2).

PMID- 20060640
TI  - Using vacuum pyrolysis and mechanical processing for recycling waste printed
      circuit boards.
AB  - The constant growth in generation of waste printed circuit boards (WPCB) poses a
      huge disposal problem because they consist of a heterogeneous mixture of organic
      and metallic chemicals as well as glass fiber. Also the presence of heavy metals,
      such as Pb and Cd turns this scrap into hazardous waste. Therefore, recycling of
      WPCB is an important subject not only from the recovery of valuable materials but
      also from the treatment of waste. The aim of this study was to present a
      recycling process without negative impact to the environment as an alternative
      for recycling WPCB. In this work, a process technology containing vacuum
      pyrolysis and mechanical processing was employed to recycle WPCB. At the first
      stage of this work, the WPCB was pyrolyzed under vacuum in a self-made batch
      pilot-scale fixed bed reactor to recycle organic resins contained in the WPCB. By
      vacuum pyrolysis the organic matter was decomposed to gases and liquids which
      could be used as fuels or chemical material resources, however, the inorganic
      WPCB matter was left unaltered as solid residues. At the second stage, the
      residues obtained at the first stage were investigated to separate and recover
      the copper through mechanical processing such as crushing, screening, and gravity
      separation. The copper grade of 99.50% with recovery of 99.86% based on the whole
      WPCB was obtained. And the glass fiber could be obtained by calcinations in a
      muffle furnace at 600 degrees C for 10 min. This study had demonstrated the
      feasibility of vacuum pyrolysis and mechanical processing for recycling WPCB.

PMID- 20060641
TI  - Physicochemical and sorption characteristics of Malaysian Ceiba pentandra (L.)
      Gaertn. as a natural oil sorbent.
AB  - Ceiba pentandra (L.) Gaertn (kapok) is a natural sorbent that exhibits excellent
      hydrophobic-oleophilic characteristics. The effect of packing density, the oil
      types and solvent treatment on the sorption characteristics of kapok was studied
      in a batch system. Oil sorption capacity, retention capacity, entrapment
      stability and kapok reusability were evaluated. Based on SEM and FTIR analyses,
      kapok fiber was shown to be a lignocellulosic material with hydrophobic waxy
      coating over the hollow structures. Higher packing density at 0.08 g/ml showed
      lower sorption capacity, but higher percentage of dynamic oil retention, with
      only 1% of oil drained out from the test cell. Kapok remained stable after
      fifteen cycles of reuse with only 30% of sorption capacity reduction. The oil
      entrapment stability at 0.08 g/ml packing was high with more than 90% of diesel
      and used engine oil retained after horizontal shaking. After 8h of chloroform and
      alkali treatment, 2.1% and 26.3% reduction in sorption capacity were observed,
      respectively, as compared to the raw kapok. The rigid hollow structure was
      reduced to flattened-like structure after alkali treatment, though no major
      structural difference was observed after chloroform treatment. Malaysian kapok
      has shown great potential as an effective natural oil sorbent, owing to high
      sorption and retention capacity, structural stability and high reusability.

PMID- 20060642
TI  - Enhanced chlorophenol sorption of soils by rice-straw-ash amendment.
AB  - Rice-straw burning is a common post-harvest practice on rice paddy land, which
      results in the accumulation of rice-straw ash (RSA) in paddy soil. Because the
      occurrence of RSA in soil may affect the fate and transport of contaminants, this
      study investigated the sorption of 3-chlorophenol (3-CP) on RSA and RSA amended
      soils to evaluate the sorptive properties of RSA in soils. The results showed
      that the sorption of 3-CP to RSA proceeds through a surface reaction rather than
      through partitioning and that the neutral form of 3-CP is preferentially sorbed
      to the surface when compared to the deprotonated anionic form of 3-CP. The
      addition of RSA to the soils enhanced the overall 3-CP sorption, indicating that
      RSA amendment may be applied to retard the movement of 3-CP in contaminated
      soils. As the RSA content in the soils was increased from 0% to 2%, the Langmuir
      sorption maximum of the soils increased from 18-80 to 256-274 mg kg(-1). Thus,
      RSA contributed more to the total sorption of the soils than other major
      components in the soils. Nonetheless, the 3-CP sorption of the soils containing
      RSA was less than the combination of pure RSA and the soils, thereby indicating
      that the 3-CP sorption of RSA was suppressed. This may be attributed to the
      competition of organic matter or other soil components for the surface binding
      sites of RSA.

PMID- 20060643
TI  - Heavy metal resistance in Arthrobacter ramosus strain G2 isolated from mercuric
      salt-contaminated soil.
AB  - Present study describes isolation of a multiple metal-resistant Arthrobacter
      ramosus strain from mercuric salt-contaminated soil. The isolate was found to
      resist and bioaccumulate several metals, such as cadmium, cobalt, zinc, chromium
      and mercury. Maximum tolerated concentrations for above metals were found to be
      37, 525, 348, 1530 and 369 microM, respectively. The isolate could also reduce
      and detoxify redox-active metals like chromium and mercury, indicating that it
      has great potential in bioremediation of heavy metal-contaminated sites. Chromate
      reductase and mercuric reductase (MerA) activities in protein extract of the
      culture were found to be 2.3 and 0.17 units mg(-1) protein, respectively. MerA
      enzyme was isolated from the culture by (NH(4))(2)SO(4) precipitation followed by
      dye affinity chromatography and its identity was confirmed by nano-LC-MS/MS. Its
      monomeric molecular weight, and optimum pH and temperature were 57kDa, 7.4 and 55
      degrees C, respectively. Thus, the enzyme was mildly thermophilic as compared to
      other MerA enzymes. K(m) and V(max) of the enzyme were 16.9 microM HgCl(2) and
      6.2 micromol min(-1)mg(-1) enzyme, respectively. The enzyme was found to be NADPH
      specific. To our knowledge this is the first report on characterization of MerA
      enzyme from an Arthrobacter sp.

PMID- 20060644
TI  - Preparation and application of cellulose triacetate microspheres.
AB  - Cellulose triacetate was prepared via reacting of a mixture of acetic anhydride
      and acetic acid containing sulfuric acid as catalyst with ramie fiber obtained
      from a biomass of ramie. The cellulose triacetate with a degree of substitution
      (DS) 2.93 of the ramie fiber was obtained. The honeycomb-like cellulose
      triacetate microspheres with an average diameter of 14 microm were made from the
      cellulose triacetate solution. The optimum conditions for preparing the
      microspheres were determined as cellulose triacetate/dichloromethane ratio 1:7
      (w/w), and 0.75% sodium dodecylsulfonate. The cellulose triacetate microspheres
      were characterized using FT-IR, NMR, XRD, and SEM. Application of the
      microspheres as an adsorbent for removing disperse dyes in water was investigated
      under the temperatures from 15 to 50 degrees C, pHs from 4 to 9, and the weight
      of cellulose triacetate microspheres from 0.03 to 0.09 g. The cellulose
      triacetate microspheres exhibited a 16.5mg/g capability to remove DR dye from
      water at 50 degrees C and pH 7.

PMID- 20060645
TI  - Heavy metals, organics and radioactivity in soil of western Serbia.
AB  - Western Serbia is a region well-known for potato production. Concentrations of
      selected metals, polycyclic aromatic hydrocarbons (PAHs) and radioactivity were
      measured in the soil in order to evaluate the quality and characteristics. The
      examined soils (Luvisol and Pseudogley) showed unsuitable agrochemical
      characteristics (acid reaction, low content of organic matter and potassium).
      Some samples contained Ni, Mn and Cr above the maximal permissible concentration
      (MPC). The average concentration of total PAHs was 1.92 mg/kg, which is larger
      than the maximal permissible concentration in Serbia but below the threshold
      values in the European Union for food production. The average radioactivity of
      (238)U, (226)Ra, (232)Th, (40)K and the fission product (137)Cs were 60.4+/-26.2,
      33.2+/-13.4, 49.1+/-18.5, 379+/-108 and 36.4+/-23.3 Bq/kg. Enhanced radioactivity
      in the soils was found. The total absorbed dose rate in air above the soil at 1m
      height calculated for western Serbia was 73.4 nGy/h and the annual effective dose
      was 90 microSv, which are similar to earlier reports for the study region.

PMID- 20060646
TI  - Modification and further evaluation of a fluorescein-labeled peanut agglutinin
      test for identification of Haemonchus contortus eggs.
AB  - Gastrointestinal nematodes of the family Trichostrongylidae are the most
      important parasites of sheep, goats and other ruminants worldwide. Of this group,
      Haemonchus contortus is usually the most damaging species, particularly in warmer
      climates or during the summer. It is therefore useful to be able to rapidly
      differentiate infections with this nematode from other, less pathogenic, species.
      However, aside from Nematodirus spp., there are only subtle differences between
      the egg morphology within the trichostrongyles, making it very difficult to
      identify eggs to the species level. It has been shown previously that peanut
      agglutinin specifically binds to Haemonchus eggs and not those of other
      trichostrongyle species. By using this lectin conjugated to fluorescein
      isothiocyanate, binding to Haemonchus eggs can be visualized under ultraviolet
      illumination. We adapted this test using eggs purified by routine sugar
      centrifugation methods and evaluated 26 diagnostic samples from ruminants
      submitted to our laboratories in Oregon and Georgia. Very good correlations were
      seen between this test and larval culture (adjusted R(2)=0.72132; F(1,25)=65.7;
      p<0.001). There was little variability between two different diagnosticians
      reading the same sample, suggesting that the test is robust and not subject to
      reader bias. An additional benefit is that eggs can be examined following
      preservation; fixation of H. contortus eggs in formalin at 0.5-5% for to up to
      4wk did not affect their staining.

PMID- 20060647
TI  - Evaluation of Deltamethrin applications in the control of tsetse and
      trypanosomosis in the southern rift valley areas of Ethiopia.
AB  - A study aimed at evaluating the efficacy of Deltamethrin (0.4% impregnated
      targets and 1% pour-on formulation) in controlling tsetse and trypanosomosis was
      carried out in two selected 10km x 10km Universal Transverse Mercator Grids of
      the Southern Tsetse Eradication Project (STEP) area in the southern rift valley
      of Ethiopia. The Grids selected were H3 (site I) and G5 (site II) in two
      districts of the Wolaita Zone. The trial was underway from September 2003 to
      April 2004. The strategy followed to accomplish the trial was a pre-intervention
      phase (entomology and parasitology) and an intervention phase with insecticide
      (Deltamethrin 0.4%)-impregnated odour-baited targets in site I and Deltamethrin
      1% 'pour-on' application to cattle in site II. The intervention phase was
      monitored on a monthly basis. Following the deployment of 460 targets at a
      density of 4 targets per km(2) in trial site I, the relative abundance of tsetse
      fly (Glossina pallidipes) declined from a pre-intervention mean catch of 1.35
      flies per trap per day to 0.05 flies per trap per day at final monitoring. These
      resulted in an 88.9% overall reduction. Similarly, an 83.25% reduction was
      recorded in the incidence of trypanosomosis in sentinel cattle as it dropped from
      10.75% (first monitoring) to 1.8% (last monitoring). The corresponding measures
      of packed cell volume (PCV) have shown a significant improvement from a mean of
      21.8% (95% confidence interval (CI): 20.7-22.9) at first monitoring to 25.5% (95%
      CI: 24.3-26.7) of last monitoring (P<0.01). In site II, the trial was started by
      spraying Deltamethrin 1% pour-on to 409 cattle at a rate of 1ml/10kg body weight.
      Pour-on treatment was repeated every month throughout the trial period. A sharp
      drop in the relative abundance of tsetse fly was revealed soon after. The catch
      was nil at fourth monitoring as it declined from 0.91 flies per trap per day of
      pre-intervention (P<0.01). A 94.9% overall reduction was achieved. The incidence
      of trypanosomosis in sentinel cattle also declined from 10% (first monitoring) to
      0.95% (last monitoring) with about 90.5% decline. An improvement in the overall
      mean PCV was seen as it rose from a mean of 24.1% (95% CI: 22.9-25.3) at first
      monitoring to 27.2% (95% CI: 26.2-28.1) at last monitoring which revealed a
      significant increase (P<0.01) until the third monitoring and maintained a stable
      state thereafter. This work finally disclosed that a relatively better efficacy
      was attained by using Deltamethrin pour-on formulation than targets in
      controlling tsetse and trypanosomiosis. However, this difference did not prove an
      apparent significance (P>0.05). So it is recommended to continue the current
      tsetse suppression by using the integrated approach of both techniques under
      consideration.

PMID- 20060648
TI  - Toxoplasma gondii and Leishmania spp. infection in captive crab-eating foxes,
      Cerdocyon thous (Carnivora, Canidae) from Brazil.
AB  - The zoonoses toxoplasmosis and leishmaniasis are important worldwide and also
      affect wild animals. Thus, the present study aimed to assess the prevalence of
      Leishmania spp. and Toxoplasma gondii antibodies in 52 serum samples from captive
      crab-eating foxes (Cerdocyon thous) kept in 17 zoos in Sao Paulo State, Brazil.
      Modified agglutination test (MAT, for toxoplasmosis) and indirect fluorescent
      antibody test (IFAT, for toxoplasmosis and leishmaniasis) were employed with
      heterologous anti-dog immunoglobulin. Antibodies to T. gondii were found in 19.2%
      animals, with an almost perfect concordance (kappa=0.86; standard error=9.31%;
      CI95%=68.25-104.76%; P<0.0001) and a strong correlation coefficient (rs=0.87;
      P<0.0001), which allows the use of heterologous anti-dog immunoglobulin to
      perform IFAT for toxoplasmosis in crab-eating foxes. No sample was positive for
      Leishmania spp. Toxoplasmosis infection occurs in wild animals from the studied
      Brazilian zoos, which indicates a probable environmental contamination,
      highlighting the importance of appropriate zoo management and the action of the
      parasite as a sentinel to human infection.

PMID- 20060649
TI  - Triple-negative breast cancer: molecular features, pathogenesis, treatment and
      current lines of research.
AB  - Breast cancer is a heterogeneous disease with different morphologies, molecular
      profiles, clinical behaviour and response to therapy. The triple negative is a
      particular type of breast cancer defined by absence of oestrogen and progesterone
      receptor expression as well as absence of ERBB2 amplification. It is
      characterized by its biological aggressiveness, worse prognosis and lack of a
      therapeutic target in contrast with hormonal receptor positive and ERBB2+ breast
      cancers. Given these characteristics, triple-negative breast cancer is a
      challenge in today's clinical practice. A new breast cancer classification
      emerged recently in the scientific scene based in gene expression profiles. The
      new subgroups (luminal, ERBB2, normal breast and basal-like) have distinct gene
      expression patterns and phenotypical characteristics. Triple-negative breast
      cancer shares phenotypical features with basal-like breast cancer, which is in
      turn the most aggressive and with worse outcome. Since microarray gene-expression
      assays are only used in the research setting, clinicians use the triple-negative
      definition as a surrogate of basal-like breast cancer. The aim of this review,
      that focuses on triple-negative breast cancer, is to summarize the most relevant
      knowledge on this particular type of cancer in terms of molecular features,
      pathogenesis, clinical characteristics, current treatments and the new
      therapeutic options that include the use of platinum compounds, EGFR antagonists,
      antiangiogenics and PARP inhibitors. Advances in research are promising and new
      types of active drugs will become a reality in the near future, making possible a
      better outcome for this subgroup of breast cancer patients.

PMID- 20060650
TI  - Perceived control moderates the influence of active coping on salivary cortisol
      response to acute pain among women but not men.
AB  - It is generally established that active-coping strategies and greater perceived
      control over pain are associated with improved pain-related outcomes; however, it
      remains unclear whether these factors independently or interactively influence
      adrenocortical function in reaction to a painful stimulus. The present study
      examined whether active coping predicted magnitude cortisol response to acute
      pain, whether perceived control over pain moderated this association, and whether
      effects differed as a function of sex. Our findings suggest that perceived
      control moderates the active coping-adrenocortical relation among women but not
      men, such that active coping may augment the release of cortisol in response to a
      painful stimulus only in the presence of greater perceived control over pain.
      Taken together, active coping and perceived control may potentiate an adaptive
      neuroendocrine response to an acute painful stressor.

PMID- 20060651
TI  - Parent-child communication and substance use among adolescents: do father and
      mother communication play a different role for sons and daughters?
AB  - The purpose of this study was to investigate gender-specific variations in the
      associations between communication with father and mother, cigarette smoking,
      alcohol drinking and marijuana use in male and female adolescents. Cross
      sectional data were collected from a national sample of 1308 tenth graders who
      participated in the 2005/06 U.S. HBSC. Outcome variables were self-reported
      substances used in the past 30 days. Logistic regression analyses controlling for
      race/ethnicity, family structure and socioeconomic status showed that the
      association of mother and father communication with adolescent substance use
      varied by substance and gender. Among sons, father communication was protective
      against marijuana use and mother communication was protective against smoking.
      Neither father nor mother communication was protective against substance use by
      daughters. Research is needed to understand gender-specific differences in
      correlates of adolescent substance use and the implications for prevention and
      intervention.

PMID- 20060652
TI  - The role of sexual intercourse in the etiology of carpal tunnel syndrome.
AB  - The etiology of non-occupational carpal tunnel syndrome is not well understood.
      It is proposed that carpal tunnel syndrome can develop during sexual intercourse
      when the hands become repeatedly extended while under pressure from the weight of
      the upper body. Of the eight risk factors associated with non-occupational carpal
      tunnel syndrome, age, marital status, pregnancy and use of hormonal agents can be
      explained by changes in the frequency of sexual intercourse. On the other hand,
      obesity, macromastia and large chest circumference can be explained by the
      increased pressure imposed on the wrists by the heavier upper body associated
      with such conditions. The bilaterality of carpal tunnel syndrome can be explained
      by the fact that both hands are needed to support the upper body during sexual
      intercourse. A parallel decrease in the frequency of sexual intercourse and the
      incidence of carpal tunnel syndrome between the sixth and the seventh decades of
      life suggests a possible cause and effect relationship between sexual intercourse
      and carpal tunnel syndrome.

PMID- 20060653
TI  - Autologous saliva transfusion: treatment for HIV?
AB  - The HIV-1 pandemic is a complex mix of diverse epidemics within and between
      countries and regions of the world, and is undoubtedly the defining public-health
      crisis of our time. Any therapeutic or prophylactic measure which holds promise
      or provides clues of eliminating or inhibiting the infection is worthy of
      investigation. As our body's own saliva is suspiciously escaping from the
      infection and providing clues regarding the resistance/inhibition of HIV; in this
      paper, a treatment approach is suggested with the rationale of in vitro effective
      antiviral action of autogenous saliva may also have a better therapeutic
      potential by its intravenous administration along with dextran.

PMID- 20060654
TI  - [Are we overusing of crash c-section procedure?].
AB  - OBJECTIVES: "Colour code" was implemented in our labour and delivery room to
      facilitate communication between the different actors of emergency c-sections
      and, more specifically, to reduce the decision to delivery interval in crash c
      sections called "red code". This study aims at evaluating "red colour" c-sections
      rate, emergency level and decision to delivery interval. PATIENTS AND METHODS:
      Over a six-months-period, all "red code" c-sections have been independently
      reviewed by four experimented obstetricians, including two external from the
      department. For each c-section, they had to confirm or reject the indication for
      "red code" c-section. Decision to delivery interval was also collected. RESULTS:
      Thirty-eight "red code" c-sections were performed representing 2.3 % of all
      deliveries and 9.1 % of all c-sections. "Red code" c-section indications have
      been confirmed in 12 cases and rejected in 13 cases. Opinions were discordant in
      the 13 others cases. Mean decision to delivery interval was 10.8 minutes.
      CONCLUSION: In our department, defining emergency level by "colour code" is
      associated with a short decision to delivery interval in crash c-sections but
      also with a trivialization of this high-risk procedure. Indications should be
      restricted to avoid unjustified maternal and foetal complications.

PMID- 20060655
TI  - The serotonin transporter gene and risk for alcohol dependence: a meta-analytic
      review.
AB  - Previous studies have implicated a relationship between particular allelic
      variations of the serotonin transporter gene (5HTTLPR) and alcohol dependence. To
      provide a current estimate of the strength of this association, particularly in
      light of inconsistent results for 5HTTLPR, we conducted a meta-analytic review of
      the association between 5HTTLPR and a clinical diagnosis of alcohol dependence.
      Of 145 studies initially identified, 22 (including 8050 participants) met
      inclusion criteria. Results indicated that there was a significant albeit modest
      association between alcohol dependence diagnosis and the presence of at least 1
      short allele (OR=1.15, 95% CI=1.01, 1.30, p<.05). Slightly more robust results
      were observed for participants who were homogeneous for the short allele
      (OR=1.21, 95% CI=1.02, 1.44, p<.05). These results were unrelated to sex and
      race/ethnicity of participants; however, the effect size was moderated by study
      sample size and publication year. Additionally, the fail-safe N analysis
      indicated potential publication bias. Therefore, although our review indicates
      that there is a significant association between 5HTTLPR and alcohol dependence
      diagnosis, this result should be interpreted with caution.

PMID- 20060656
TI  - Association of polymorphisms of the serotonergic system with smoking initiation
      in Caucasians.
AB  - BACKGROUND: The serotonergic system may be implicated in susceptibility to
      nicotine dependence as nicotine increases 5-hydroxytryptamine (5-HT) release in
      brain and symptoms of nicotine withdrawal may be modulated by diminished
      serotonergic neurotransmission. We examined the association of polymorphisms of
      genes involved in release and receptor function of 5-HT with cigarette smoking
      initiation in subjects of Caucasian origin. METHODS: 5-HTTLPR polymorphism of the
      5-HT transporter gene and -759C/T (rs3813929) and -697G/C (rs518147)
      polymorphisms of the 5-HT(2C) receptor gene were analyzed in 172 smoking
      initiators and 254 non-initiators, using PCR-RFLP method. Smoking behavior was
      assessed with a questionnaire about tobacco use. RESULTS: We found no differences
      in the frequency of the 5-HTTLPR genotypes between smoking initiators and non
      initiators. However, the frequency of 5-HT(2C) -759T allele was significantly
      higher in non-initiators than smoking initiators (29.5% vs 16.3%, p=0.002) and
      the same was true for 5-HT(2C) -697C allele carriers (48.8% vs 34.9%, p=0.004).
      Sex-dependent analysis revealed that these increased frequencies of -759T and 
      697C allele carriers were present only in males. No association was observed
      between any quantitative measures of smoking and these three polymorphisms.
      CONCLUSIONS: 5-HTTLPR polymorphism was not associated with smoking initiation in
      either male or female subjects. However, significant association was found
      between 5-HT(2C) receptor gene polymorphisms and smoking initiation in male
      Caucasian subjects.

PMID- 20060658
TI  - Small ruminant lentivirus genotype E is widespread in Sarda goat.
AB  - The highly divergent SRLV genotype E has recently been characterized in Italy as
      a low pathogenic caprine lentivirus in the Roccaverano breed. The availability of
      a genotype specific diagnostic test based on a comparative assay, using a
      combination of genotype specific recombinant antigens allows a wide serosurvey in
      other goat populations. The island of Sardinia still has the highest small
      ruminant population of any Italian region and crossbreeding has been limited to
      goats, mainly with the Maltese breed. A serological survey was carried out on
      sheep flocks and goat herds, using individual sera as well as a bulk milk-adapted
      procedure. Genotype E was identified in more than 50% of goat herds and none of
      the sheep flocks thus supporting the idea that this genotype is specifically
      associated with the goat species. The full-length proviral sequence of a
      Sardinian isolate revealed and confirmed the deletion of dUTPase subunit and the
      absence of both vpr gene and the 71bp repeat of the LTR. Genetic similarity of
      this isolate with the prototype strain Roccaverano was not more than 84%,
      supporting the designation of two subtypes within genotype E. Nevertheless, in
      vitro properties of the Sardinian strain were different from those of the
      Roccaverano strain in terms of ability to infect synovial membrane and produce
      syncitia. Remarkable differences in the HV1 and HV2 of the env gene were
      recorded, with the Sardinian isolate displaying sequence motif more similar to
      arthritic strains. Data presented suggest diffusion of genotype E is wider than
      previously thought.

PMID- 20060657
TI  - Evaluating the drug use "gateway" theory using cross-national data: consistency
      and associations of the order of initiation of drug use among participants in the
      WHO World Mental Health Surveys.
AB  - BACKGROUND: It is unclear whether the normative sequence of drug use initiation,
      beginning with tobacco and alcohol, progressing to cannabis and then other
      illicit drugs, is due to causal effects of specific earlier drug use promoting
      progression, or to influences of other variables such as drug availability and
      attitudes. One way to investigate this is to see whether risk of later drug use
      in the sequence, conditional on use of drugs earlier in the sequence, changes
      according to time-space variation in use prevalence. We compared patterns and
      order of initiation of alcohol, tobacco, cannabis, and other illicit drug use
      across 17 countries with a wide range of drug use prevalence. METHOD: Analyses
      used data from World Health Organization (WHO) World Mental Health (WMH) Surveys,
      a series of parallel community epidemiological surveys using the same instruments
      and field procedures carried out in 17 countries throughout the world. RESULTS:
      Initiation of "gateway" substances (i.e. alcohol, tobacco and cannabis) was
      differentially associated with subsequent onset of other illicit drug use based
      on background prevalence of gateway substance use. Cross-country differences in
      substance use prevalence also corresponded to differences in the likelihood of
      individuals reporting a non-normative sequence of substance initiation.
      CONCLUSION: These results suggest the "gateway" pattern at least partially
      reflects unmeasured common causes rather than causal effects of specific drugs on
      subsequent use of others. This implies that successful efforts to prevent use of
      specific "gateway" drugs may not in themselves lead to major reductions in the
      use of later drugs.

PMID- 20060659
TI  - Serological, pathological and polymerase chain reaction studies on Mycoplasma
      hyopneumoniae infection in the wild boar.
AB  - There are evidences that wild boar and domestic pig populations share the
      vulnerability to certain pathogens and, in consequence, the risk of pathogen
      transmission. Based on serological evidences, it is known that Mycoplasma
      hyopneumoniae (Mhyo) is able to infect the wild boar. However, if this infection
      causes lesions and disease in this species is still unknown. The objectives of
      the present study were to assess the seroprevalence to Mhyo, as well as the rates
      of detection of Mhyo (by nested polymerase chain reaction, nPCR) in upper and
      lower respiratory tract of the wild boar. Moreover, presence of enzootic
      pneumonia (EP)-like gross and microscopic lesions in these animals was also
      assessed. Antibodies against Mhyo were detected in 92 out of 428 (21%) serum
      samples tested. Moreover, Mhyo DNA was detected by nPCR in 17 out of 85 (20%)
      nasal swabs and in 12 out of 156 (8%) lung samples. No gross EP-like lesions were
      observed in any of the studied pigs. Besides, presence of EP-like microscopic
      lung lesions was observed in 18 out of 63 (29%) animals. Mhyo DNA was detected at
      lung level in 2 out of these 18 (11%) animals. Presence of EP-like microscopic
      lesions was significantly related (p<0.05) with Mhyo detection at nasal swab swab
      but not (p>0.05) with its detection in lung samples; such lesions were also
      linked (p<0.05) with presence of Metastrongylus spp.-like parasite structures.
      Results of the present study confirm that Mhyo is able to infect and might be
      able to cause EP-like microscopic lesions in wild boar but, apparently, with a
      subclinical impact.

PMID- 20060660
TI  - Pyrosequencing of the Vir plasmid of necrotoxigenic Escherichia coli.
AB  - Necrotoxigenic Escherichia coli, or NTEC, are defined as E. coli producing the
      toxin known as cytotoxic necrotizing factor, or CNF. NTEC are responsible for
      various diseases of humans and animals, including urinary tract infection,
      septicemia, and diarrhea. A subgroup of NTEC known as NTEC-2 produce a variant of
      CNF (CNF-2) whose gene is located on a plasmid known as Vir. Because of its
      involvement in NTEC-2 pathogenesis and its broad distribution among production
      animals, a Vir plasmid from a bovine NTEC-2 strain was sequenced and analyzed.
      This plasmid was found to belong to the RepFIB and RepFIIA replicon types, and it
      totaled 138,682 base pairs in size. Within this plasmid was an approximately 60
      kb pathogenicity island, defined by its possession of multiple virulence factors
      within distinct genetic regions of lower G+C content bounded by inverted repeats.
      Within this PAI were a variety of putative virulence factors, including F17b
      fimbrial genes, genes of a novel fimbrial operon, tibAC, hemolysins, and the cnf2
      and cdt toxin-encoding genes. The occurrence of this plasmid's virulence- and
      replication-associated genes was sought among a collection of 96 CNF-2-positive
      isolates. The most prevalent genes among this collection included repA (RepFIB),
      cnf2, an ompP homolog, and the tib-AC genes encoding for aggregation and biofilm
      formation. The Vir plasmid has evolved from an IncFIB ancestral backbone, with
      the RepFIB locus apparently driving the acquisition of its accessory virulence
      associated elements via site-specific recombination. Overall, the completed
      sequence of a Vir plasmid increases our understanding of NTEC-2 pathogenomics and
      IncFIB plasmid evolution.

PMID- 20060661
TI  - Phylogenetic analysis of the haemagglutinin gene of current wild-type canine
      distemper viruses from South Africa: lineage Africa.
AB  - There are no reports of CDV isolations in southern Africa, and although CDV is
      said to have geographically distinct lineages, molecular information of African
      strains has not yet been documented. Viruses isolated in cell cultures were
      subjected to reverse transcription-polymerase chain reaction (RT-PCR), and the
      complete H gene was sequenced and phylogenetically analysed with other strains
      from GenBank. Phylogenetic comparisons of the complete H gene of CDV isolates
      from different parts of the world (available in GenBank) with wild-type South
      African isolates revealed nine clades. All South African isolates form a separate
      African clade of their own and thus are clearly separated from the American,
      European, Asian, Arctic and vaccine virus clades. It is likely that only the
      'African lineage' of CDV may be circulating in South Africa currently, and the
      viruses isolated from dogs vaccinated against CDV are not the result of reversion
      to virulence of vaccine strains, but infection with wild-type strains.

PMID- 20060662
TI  - Prevalence of equine adenovirus antibodies in horses in New South Wales,
      Australia.
AB  - There are currently two known serotypes of equine adenovirus (EAdV), equine
      adenovirus type 1 (EAdV1) and equine adenovirus type 2 (EAdV2); EAdV1 is
      predominantly associated with upper respiratory tract infections while EAdV2
      appears to have a higher association with gastrointestinal infection, however,
      very little is known about the prevalence of these viruses in horse populations
      in Australia. In this study we tested 122 serum samples obtained from horses in
      New South Wales, Australia, using a standard serum neutralization (SN) assay and
      ELISA. Ninety-seven of the 122 sera displayed had moderate to high titers of
      antibodies to EAdV1 and/or EAdV2. Eighteen of the 122 sera were positive for both
      EAdV1 and EAdV2. In contrast, only thirty-seven positive samples were detected
      using the ELISA. These results suggest that EAdV1 and EAdV2 infections are widely
      prevalent in the horse population tested and that SN is currently the most
      suitable assay for the detection of EAdV1 and EAdV2 antibodies in equine serum.

PMID- 20060663
TI  - High pre-freezing dilution improves post-thaw function of ram spermatozoa.
AB  - Despite considerable cryobiology research there is no industry standard for the
      concentration to which ram spermatozoa should be diluted before freezing. Ram
      semen is highly concentrated and often frozen at a high sperm concentration,
      necessitating the use of small laparoscopic insemination doses. The aim of this
      paper was to ascertain the effect of dilution on the integrity of frozen-thawed
      ram spermatozoa. In the first experiment, spermatozoa were extended with a Tris
      buffered diluent before freezing or after thawing to yield a final sperm
      concentration of 20 x 10(6)/ml, or were not diluted. Motility characteristics,
      viability and acrosome integrity of spermatozoa were analysed over a 6h
      incubation period at 37 degrees C. In the second experiment, spermatozoa were
      either diluted before freezing, subjected to sex-sorting or not diluted before
      freezing. Thawed spermatozoa were separated into sub-populations using
      centrifugal counter-current distribution (CCCD) and the profile of partition and
      functional integrity (viability, chlortetracycline status and Annexin-V binding)
      in the sub-populations assessed. Dilution before freezing significantly improved
      post-thaw viability, acrosome integrity and total motility whereas dilution post
      thaw decreased viability and motility of spermatozoa. Sperm heterogeneity, as
      assessed by CCCD profile, was not different for control, diluted and sex-sorted
      spermatozoa. Analysis of CCCD sub-populations showed the proportion of functional
      cells (displaying the F-Pattern or no PS translocation) was similar for all sperm
      types. The results show that ram spermatozoa retain normal function at higher pre
      freeze dilution rates than are commonly used in the sheep industry. The
      application of these findings would result in more practicable and functional
      artificial insemination doses.

PMID- 20060664
TI  - A rapid method for sexing the bovine embryo.
AB  - This study aimed to detect the sex of bovine embryo by adding ethidium bromide
      (EB) or 5 microl of CuSO(4) at different concentrations (0.5 M, 1 M, 1.5 M, 2 M,
      3 M and 5 M) to the product of loop-mediated isothermal amplification (LAMP)
      reaction. The result of these additions was a colour change and a precipitate.
      This allows detection with the naked eye without the use of electrophoresis or a
      turbidity meter. The in vitro produced bovine embryos were divided into one to
      eight pieces using a microblade attached to a micromanipulator. The cell number
      in each piece was counted before sexing. Sexing of DNA samples extracted from one
      to five biopsies cells was performed by LAMP. After biopsy, the remaining part of
      the embryos was used to confirm the sex by polymerase chain reaction (PCR). The
      time for the whole procedure was about 45 min. LAMP is a novel DNA amplification
      method which amplifies a target sequence specifically under isothermal condition.
      We used this method to examine 58 bovine embryos and the accuracy of sex
      prediction was 100% when the blastomeres dissociated from a morula exceeds three.
      This study showed that the present method can be applied in bovine breeding
      programs to facilitate manipulation of the sex ratio of offspring. The aim of
      this study is to develop an improved embryo sexing technique based on the LAMP
      reaction. This new method is economic and more suitable for field application
      without turbidity meter or electrophoresis.

PMID- 20060665
TI  - Does daily vitamin D 800 IU and calcium 1000 mg supplementation decrease the risk
      of falling in ambulatory women aged 65-71 years? A 3-year randomized population
      based trial (OSTPRE-FPS).
AB  - OBJECTIVE: The hypothesis was that the calcium and vitamin D supplementation
      prevents falls at the population level. STUDY DESIGN: The OSTPRE-FPS was a
      randomized population-based open-trial with 3-year follow-up. The supplementation
      group (n=1566) received daily cholecalciferol 800IU+calcium carbonate 1000mg,
      while the control group (n=1573) received no supplementation or placebo. A
      randomly selected subsample of 593 subjects underwent a detailed measurement
      program including serum 25(OH)D measurements. MAIN OUTCOME MEASURE: The
      occurrence of falls was the primary outcome of the study. The participants in the
      subsample were telephoned at 4 months intervals and the rest of the trial
      population was interviewed by phone once a year. RESULTS: In the entire trial
      population (ETP), there were 812 women with 1832 falls in the intervention group
      and 833 women with 1944 falls in the control group (risk ratio was 0.98, 95% CI
      0.92-1.05, P=0.160). The supplementation was not associated with single or
      multiple falls in the ETP. However, in the subsample, multiple fall incidence
      decreased by 30% (odds ratio (OR) 0.70, 95% CI 0.50-0.97, P=0.034) in the
      supplementation group. Further, the supplementation decreased the incidence of
      multiple falls requiring medical attention (OR 0.72, 95% CI 0.53-0.97, P=0.031)
      in the ETP. The mean compliance in the entire trial population was 78% and in the
      subsample 79%. DISCUSSION: Overall, the primary analysis showed no association
      between calcium and vitamin D supplementation and risk of falls. However, the
      results of a post hoc analysis suggested that there was a decreased risk of
      multiple falls requiring medical attention: this finding requires confirmation.

PMID- 20060666
TI  - Plant sterols and stanols for healthy ageing.
AB  - The proportion of elderly is growing worldwide. This trend is in parallel to an
      increase in diseases, such as cardiovascular disease (CVD). Plant sterols and
      stanols (PS) consumption is known to decrease low-density lipoprotein-cholesterol
      (LDL-C) levels by 5-15%, and thus lower CVD risk. Yet, the effect of PS on LDL-C
      levels differs between individuals. Furthermore, PS have recently been
      investigated for the prevention of other age-related diseases. The objective of
      this review is to examine the benefits of PS on CVD as well as ageing-associated
      diseases. PS have the ability to significantly lower LDL-C; yet, the large inter
      individual variability in the lowering of LDL-C may be due to subject
      characteristics, food matrix of PS, dose of PS, dietary background, frequency of
      intake of PS, the additive effect of other foods or drugs, as well as genetic
      factors. Further, PS may also have other potential beneficial effects including
      anti-atherogenic, anti-inflammatory, antioxidant and anti-cancer activities.
      Overall, dietary intervention strategies, such as incorporating PS into a healthy
      diet, should be recommended and implemented in older adult populations in order
      to prevent ageing-associated diseases and hence promote healthy ageing.

PMID- 20060667
TI  - A review of acupuncture for menopausal problems.
AB  - Acupuncture is one of the complementary therapies that are increasingly used by
      women with menopausal hot flushes. Acupuncture can be understood as a form of
      neurological stimulation. Clinical trials of acupuncture use different control
      groups according to whether they wish to provide practical information on the
      role of acupuncture in health care, or theoretical information on the specific
      needle effect. Controls for the latter research question are highly problematic,
      and no convincingly inert 'placebo' needle has yet been designed. For natural
      menopause, one large study has shown acupuncture to be superior to self-care
      alone in reducing the number of hot flushes and improving the quality of life;
      five small studies have been unable to demonstrate that the effect of acupuncture
      is limited to any particular points, as traditional theory would suggest; and one
      study showed acupuncture was superior to blunt needle for flash frequency but not
      intensity. For flushes associated with induced menopause, clearly acupuncture is
      useful for reducing flushes in clinical practice, but there is mixed evidence on
      the nature of the effect: one trial found genuine acupuncture superior to control
      needling, but another showed no significant difference between acupuncture and
      blunt needle. The possible mechanisms of acupuncture for hot flushes are
      discussed. Current evidence clearly justifies further research into the most cost
      effective form of acupuncture for treating hot flushes.

PMID- 20060668
TI  - Forensic handwriting examiners' opinions on the process of production of
      disguised and simulated signatures.
AB  - Large-scale blind testing of forensic handwriting examiners (FHEs) has shown that
      authorship opinions on disguised and simulated signatures attract higher
      misleading and inconclusive rates than genuine signatures do. To test whether
      this is due to the failure of FHEs to detect the indicators of
      disguise/simulation behaviours we examined their opinions regarding the 'process
      of production' (which in this case was a choice between written naturally or
      written using a disguise/simulation strategy) of the questioned disguised and
      simulated signatures in blinded skill testing trials. The relationship between
      their process opinions and authorship opinions is then assessed. It was found
      that the majority of the inconclusive authorship opinions for both disguised and
      simulated signatures had a correct process opinion (707 of 1241, 57.0% for
      disguised; 3838 of 4368, 87.9% for simulated), with only 7.3% (90 of 1241) of the
      disguised and 0.85% (37 of 4368) of the simulated signatures exhibiting incorrect
      process opinions. For the total misleading authorship opinions relating to
      disguised signatures, the majority of the process opinions were correct (167 of
      241, 69.3%) indicating that a disguise/simulation process was detected, but
      misinterpreted as being by another writer. These results show the usefulness of
      FHEs offering a first stage simulation/disguise process opinion without going on
      to form an opinion on authorship, as the support for the proposition that a
      signature is something other than genuine may be, in itself, of strong evidential
      value.

PMID- 20060669
TI  - Simultaneous extraction of trace organophosphorous pesticides from plasma sample
      by automated solid phase extraction and determination by gas chromatography
      coupled with pulsed flame photometric detector.
AB  - The purpose of our work was to develop a simple and efficient analytical method
      for simultaneous determination of different species of organic phosphorus
      pesticides from plasma sample by using automated solid phase extraction (SPE) and
      gas chromatography/pulsed flame photometric detector (GC/PFPD) as a diagnostic
      tool. Firstly, the developed extraction method was validated using 5 certified
      reference materials; then, it was applied to plasma sample. Such factors as the
      category and volume of wash and elution solvent were examined separately. Among
      these factors, the category of elution solvent is most important. Hexane-acetone
      (50:50, v/v) seems to be the best choice for it. The eluent was evaporated on a
      nitrogen stream at room temperature and redissolved by acetone. 1microL of
      aliquots was chromatographed on GC/PFPD. Response versus the amount of pesticides
      injected ranging from 0.05 to 2ng showed a good linearity. The detection limits
      were 0.01ng for dimethoate, 0.03ng for methyl-parathion and malathion, 0.04ng for
      terbufos and 0.02ng for parathion. Extraction recoveries range from 84.3% to
      109.1%.This extraction method for multispecies analysis incorporates many
      benefits in terms of speed, low solvent use, accuracy of measurement,
      sensitivity, relative simplicity, as well as the time saving and convenience of
      multiple species measurement through sample preparation and analysis as an
      integrated step.

PMID- 20060670
TI  - Changes in antidepressant metabolism in pregnancy evidenced by metabolic ratios
      in hair: a novel approach.
AB  - BACKGROUND: Depression and other psychiatric illnesses are common during
      pregnancy and are often treated with antidepressants. Physiological changes of
      pregnancy may alter the pharmacokinetics of medications and ultimately affect the
      dose required to maintain effective therapy. Human hair offers a safe, non
      invasive way to monitor long term systemic exposures to medications. OBJECTIVE:
      To determine whether the ratio of hair antidepressant: major metabolite differed
      when early and late pregnancy was compared to the postpartum period. METHODS:
      Segmental analyses using liquid chromatography-mass spectrometry-mass
      spectrometry were performed on hair samples. The mean concentration of parent
      compound and metabolite was found for each trimester and the postpartum period.
      RESULTS: Twelve women provided hair samples of which nine samples were long
      enough to analyze the first and third trimesters along with the postpartum
      period. Citalopram, venlafaxine, fluoxetine and sertraline were the
      antidepressants studied. In the citalopram group, a statistically significant
      difference existed between the citalopram:norcitalopram ratio when the first
      trimester was compared to the postpartum period (0.89+/-0.26 versus 1.4+/-0.24
      respectively, p=0.022). A statistically significant difference also existed
      between the third trimester and the postpartum period for the citalopram group
      (0.9+/-0.14 and 1.4+/-0.24 respectively, p=0.048). No other statistically
      significant differences were found. CONCLUSION: It is important that variations
      in drug metabolism during pregnancy be considered as these changes may
      necessitate a dosage adjustment to ensure that therapeutic failure does not occur
      during pregnancy.

PMID- 20060671
TI  - Dental age assessment among Iranian children aged 6-13 years using the Demirjian
      method.
AB  - BACKGROUND: Many methods of age estimation have been suggested, and of these, the
      Demirjian method is the most frequently used. The objective of the present study
      is to test the accuracy of the Demirjian method for age estimation in an Iranian
      population. MATERIALS AND METHODS: A cross-sectional study involving 141 boys and
      170 girls selected by a convenience sampling method was carried out. Panoramic
      radiography was used to score the left mandibular teeth and to obtain the
      Demirjian tooth age. RESULTS: The Demirjian method overestimated the age of boys
      by 0.34 years and girls by 0.25 years. The scatter plots showing the difference
      between estimated dental age and chronological age for boys and girls showed that
      the regression lines had a decreasing trend with age. The mean difference between
      estimated dental age and chronological age in boys decreased with age (except in
      the oldest age group of boys). In contrast, it increased in girls between the
      ages of 6-8 years old, and then decreased. CONCLUSION: The results show that the
      Demirjian method is appropriate for estimating the dental age of patients,
      especially those belonging to the 9-13 year old age group. However, in the
      younger age groups, further study involving more cases is required.

PMID- 20060672
TI  - Migration of epileptic spike foci in encephalograms may correlate with a better
      outcome in pediatric epilepsy.
AB  - Epileptic spike foci in children can be fixed in specific brain regions or
      migrate over time. We analyzed 969 encephalograms from 463 epileptic children to
      determine outcome differences between those with fixed foci (FF) and those with
      migrated foci (MF) on at least three encephalograms over 3years. All epileptic
      spike foci were classified as frontal, temporal, central, parietal, or occipital.
      Migration directions were divided into anterior, posterior, lateral, and
      unclassified. Seventy-nine cases met the inclusion criteria: 24 (30%) FF and 55
      (70%) MF. More patients in the FF than in the MF group required multiple
      antiepileptic drugs (P=0.004), and had abnormal image findings (P=0.014), mental
      retardation (P=0.035), and worse seizure control (P=0.047). Seizure frequency
      (P=0.007; correlation coefficient=0.56) and the number of prescribed drugs
      (P=0.047; correlation coefficient=0.372) were more significant in the FF group
      than in the MF group. When we compared only whether the cases were symptomatic or
      cryptogenic, we found the same outcome trends. In comparisons of only idiopathic
      epileptic patients, the FF group had non-significantly different outcomes
      compared with those in the MF group. When we compared 16 cases of benign
      childhood epilepsy with centrotemporal spikes (BECTs) and 8 Panayiotopoulos
      syndrome (PS), the cases with BECTs had more FF (38% vs. 0%, P=0.03). We conclude
      that outcomes may not correlate as well in FF cases as they do in MF cases.
      Idiopathic epilepsy warrants more study.

PMID- 20060673
TI  - Unexpected neurological sequelae following propofol anesthesia in infants: Three
      case reports.
AB  - Propofol is a widely used hypnotic agent for induction and maintenance of
      pediatric anesthesia with a well known safety profile. Experimental in vitro
      studies suggest that propofol may be toxic to developing neurons. We report the
      cases of three infants who underwent surgery before 2 months of age for different
      benign pathologies. Propofol was used for induction and maintenance of anesthesia
      in all cases. The three patients developed convulsions with similar clinical
      characteristics (cluster of recurrent clinical and subclinical seizures) between
      the 23th and 30th hours following anesthesia. Clinical and
      electroencephalographic improvement was obtained between the third and fourth day
      of management in pediatric intensive care unit. The seizures never recurred, and
      the three patients underwent further uneventful general anesthesia without
      propofol. Follow-up of the three patients disclosed unexpected neurological
      dysfunction: progressive microcephaly (head circumferences were normal at birth),
      developmental impairment with cognitive and behavioural disturbances in two
      cases, and bilateral symmetrical white-matter abnormalities on cerebral magnetic
      resonance imaging. CONCLUSION: The causal relationship between propofol
      anesthesia and the neurological symptoms of our patients remains difficult to
      ascertain, but we believe that pediatricians, anesthetists and intensive care
      givers should be aware of this possible adverse reaction that has never been
      described before.